PMID- 24559318
TI  - Particles decorated by an ionizable thermoresponsive polymer brush in water:
      experiments and self-consistent field modeling.
AB  - We have synthesized anionic multistimuli responsive core-shell polymer
      nanoparticles with low size dispersity composed of glassy poly(methyl
      methacrylate) (PMMA) cores of ca. 40 nm radius and poly(N-isopropylacrylamide)
      (PNIPAM) anionic brush-like shells with methacrylic acid comonomers. Using
      dynamic light scattering, we observed a volume phase transition upon an increase
      in temperature and this response was pH and ionic strength dependent. Already at
      room temperature we observed a pronounced polyelectrolyte effect, that is, a
      shift of the apparent pKa extracted from the degree of dissociation of the acids
      as a function of the pH. The multiresponsive behavior of the hydrophobic
      polyelectrolyte brush has been modeled using the Scheutjens-Fleer self-consistent
      field (SF-SCF) approach. Using a phenomenological relation between the Flory
      Huggins chi parameter and the temperature, we confront the predicted change in
      the brush height with the observed change of the hydrodynamic radius and degree
      of dissociation and obtain estimates for the average chain lengths (number of
      Kuhn segments) of the corona chains, the grafting density and charge density
      distributions. The theory reveals a rich internal structure of the hydrophobic
      polyelectrolyte brush, especially near the collapse transition, where we find a
      microphase segregated structure. Considering this complexity, it is fair to state
      that the theoretical predictions follow the experimental data semiquantitatively,
      and it is attractive to attribute the observed disparity between theory and
      experiments to the unknown polydispersity of the chains, the unknown distribution
      of the charges, or other experimental complications. More likely, however, the
      deviations point to significant problems of the mean field theory, which focuses
      solely on the radial distributions and ignores the possibility of the formation
      of lateral (local) inhomogeneities in partially collapsed polyelectrolyte
      brushes. We argue that the PNIPAM brush at room temperature is already behaving
      nonideally. 

PMID- 24559317
TI  - Identification of novel and conserved miRNAs involved in pollen development in
      Brassica campestris ssp. chinensis by high-throughput sequencing and degradome
      analysis.
AB  - BACKGROUND: microRNAs (miRNAs) are endogenous, noncoding, small RNAs that have
      essential regulatory functions in plant growth, development, and stress response
      processes. However, limited information is available about their functions in
      sexual reproduction of flowering plants. Pollen development is an important
      process in the life cycle of a flowering plant and is a major factor that affects
      the yield and quality of crop seeds. RESULTS: This study aims to identify miRNAs
      involved in pollen development. Two independent small RNA libraries were
      constructed from the flower buds of the male sterile line (Bcajh97-01A) and male
      fertile line (Bcajh97-01B) of Brassica campestris ssp. chinensis. The libraries
      were subjected to high-throughput sequencing by using the Illumina Solexa system.
      Eight novel miRNAs on the other arm of known pre-miRNAs, 54 new conserved miRNAs,
      and 8 novel miRNA members were identified. Twenty-five pairs of novel
      miRNA/miRNA* were found. Among all the identified miRNAs, 18 differentially
      expressed miRNAs with over two-fold change between flower buds of male sterile
      line (Bcajh97-01A) and male fertile line (Bcajh97-01B) were identified. qRT-PCR
      analysis revealed that most of the differentially expressed miRNAs were
      preferentially expressed in flower buds of the male fertile line (Bcajh97-01B).
      Degradome analysis showed that a total of 15 genes were predicted to be the
      targets of seven miRNAs. CONCLUSIONS: Our findings provide an overview of
      potential miRNAs involved in pollen development and interactions between miRNAs
      and their corresponding targets, which may provide important clues on the
      function of miRNAs in pollen development.

PMID- 24559319
TI  - MB109 as bioactive human bone morphogenetic protein-9 refolded and purified from
      E. coli inclusion bodies.
AB  - BACKGROUND: The development of chemical refolding of transforming growth factor
      beta (TGF-beta) superfamily ligands has been instrumental to produce the
      recombinant proteins for biochemical studies and exploring the potential of
      protein therapeutics. The osteogenic human bone morphogenetic protein-2 (hBMP-2)
      and its Drosophila DPP homolog were the early successful cases of refolding into
      functional form. Despite the similarity in their three dimensional structure and
      amino acid sequences, several other TGF-beta superfamily ligands could not be
      refolded readily by the same methods. RESULTS: Here, we report a comprehensive
      study on the variables of a rapid-dilution refolding method, including the
      concentrations of protein, salt, detergent and redox agents, pH, refolding
      duration and the presence of aggregation suppressors and host-cell contaminants,
      in order to identify the optimal condition to refold human BMP-9 (hBMP-9). To
      produce a recombinant form of hBMP-9 in E. coli cells, a synthetic codon
      optimized gene was designed to encode the mature domain of hBMP-9 (Ser320 -
      Arg429) directly behind the first methionine, which we herein referred to as
      MB109. An effective purification scheme was also developed to purify the refolded
      MB109 to homogeneity with a final yield of 7.8 mg from 100 mg of chromatography
      purified inclusion bodies as a starting material. The chemically refolded MB109
      binds to ALK1, ActRIIb and BMPRII receptors with relatively high affinity as
      compared to other Type I and Type II receptors based on surface plasmon resonance
      analysis. Smad1-dependent luciferase assay in C2C12 cells shows that the MB109
      has an EC50 of 0.61 ng/mL (25 pM), which is nearly the same as hBMP-9.
      CONCLUSION: MB109 is prone to be refolded as non-functional dimer and higher
      order multimers in most of the conditions tested, but bioactive MB109 dimer can
      be refolded with high efficiency in a narrow window, which is strongly dependent
      on the pH, refolding duration, the presence of aggregation suppressors and the
      concentrations of protein, salt and detergent. These results add to the current
      understanding of producing recombinant TGF-beta superfamily ligands in the
      microbial E. coli system. An application of the technique to produce a large
      number of synthetic TGF-beta chimeras for activity screen is also discussed.

PMID- 24559321
TI  - Evaluation of an early step-down strategy from intravenous anidulafungin to oral
      azole therapy for the treatment of candidemia and other forms of invasive
      candidiasis: results from an open-label trial.
AB  - BACKGROUND: Hospitalized patients are at increased risk for candidemia and
      invasive candidiasis (C/IC). Improved therapeutic regimens with enhanced clinical
      and pharmacoeconomic outcomes utilizing existing antifungal agents are still
      needed. METHODS: An open-label, non-comparative study evaluated an intravenous
      (i.v.) to oral step-down strategy. Patients with C/IC were treated with i.v.
      anidulafungin and after 5 days of i.v. therapy had the option to step-down to
      oral azole therapy (fluconazole or voriconazole) if they met prespecified
      criteria. The primary endpoint was the global response rate (clinical +
      microbiological) at end of treatment (EOT) in the modified intent-to-treat (MITT)
      population (at least one dose of anidulafungin plus positive Candida within 96
      hours of study entry). Secondary endpoints included efficacy at other time points
      and in predefined patient subpopulations. Patients who stepped down early (<= 7
      days' anidulafungin) were identified as the "early switch" subpopulation.
      RESULTS: In total, 282 patients were enrolled, of whom 250 were included in the
      MITT population. The MITT global response rate at EOT was 83.7% (95% confidence
      interval, 78.7-88.8). Global response rates at all time points were generally
      similar in the early switch subpopulation compared with the MITT population.
      Global response rates were also similar across multiple Candida species,
      including C. albicans, C. glabrata, and C. parapsilosis. The most common
      treatment-related adverse events were nausea and vomiting (four patients each).
      CONCLUSIONS: A short course of i.v. anidulafungin, followed by early step-down to
      oral azole therapy, is an effective and well-tolerated approach for the treatment
      of C/IC. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00496197.

PMID- 24559322
TI  - Regorafenib in metastatic colorectal cancer.
AB  - Regorafenib is an oral multikinase inhibitor that blocks the activity of protein
      kinases involved in the regulation of tumor angiogenesis (VEGFR1, 2, 3;
      angiopoietin-1 receptor), oncogenesis (stem cell growth factor receptor; RET;
      BRAF including BRAFV600E), and tumor microenvironment (PDGFR-beta and FGFR).
      Based on data from the Phase III CORRECT study, regorafenib stands as a further
      option for patient affected by metastatic colorectal cancer who have exhausted
      previous available therapies. Its multi-targeted effect might explain activity in
      advanced lines of treatment, when cancer cells have been heavily challenged with
      previous lines of therapy and potentially developed multiple mechanisms of
      resistance, but also makes difficult to identify predictive biomarkers. In this
      article we examine preclinical as well as clinical data of regorafenib in the
      therapy of metastatic colorectal cancer, challenges for potential markers of
      efficacy and its role in the treatment algorithm. 

PMID- 24559320
TI  - Matricellular protein thrombospondins: influence on ocular angiogenesis, wound
      healing and immuneregulation.
AB  - Thrombospondins are a family of large multi-domain glycoproteins described as
      matricelluar proteins based on their ability to interact with a broad range of
      receptors, matrix molecules, growth factors or proteases, and to modulate array
      of cellular functions including intracellular signaling, proliferation and
      migration. Two members of the thrombospondin family, thrombospondin 1 (TSP-1) and
      thrombospondin 2 (TSP-2) are studied extensively to determine their structure and
      function. While expressed at low levels in normal adult tissues, their increased
      expression is seen predominantly in response to cellular perturbations. Despite
      structural similarities, a notable functional difference between TSP-1 and TSP-2
      includes the ability of former to activate of latent TGF-beta and its competitive
      inhibition by the latter. Both these thrombospondins are reported to play
      important roles in TGF-beta rich ocular environment with most reports related to
      TSP-1. They are expressed by many ocular cell types and detectable in the aqueous
      and vitreous humor. TSP-1 and TSP-2 influence many cellular interactions in the
      eye such as angiogenesis, cell migration, wound healing, TGF-beta activation and
      regulation of inflammatory immune responses. Together, these processes are known
      to contribute to the immune privilege status of the eye. Emerging roles of TSP-1
      and TSP-2 in ocular functions and pathology are reviewed here.

PMID- 24559323
TI  - Management for premalignant lesions of the oral cavity.
AB  - Premalignant lesions of the oral cavity present as visibly abnormal areas of
      mucosa and may be a source of significant anxiety for the patient and the
      clinician. Suspicious lesions should be biopsied to evaluate for dysplasia. The
      risk of malignant transformation may relate to patient characteristics,
      environmental risk factors and genetic alterations. Management of such lesions
      hinges on risk modification, surveillance, symptom management and directed
      biopsies. Excision or ablation of dysplastic lesions is indicated. We review the
      current evidence relating to management of premalignant lesions of the oral
      mucosa and make recommendations for practice patterns. 

PMID- 24559325
TI  - Surface-chemistry effect on cellular response of luminescent plasmonic silver
      nanoparticles.
AB  - Cellular response of inorganic nanoparticles (NPs) is strongly dependent on their
      surface chemistry. By taking advantage of robust single-particle fluorescence and
      giant Raman enhancements of unique polycrystalline silver NPs (AgNPs), we
      quantitatively investigated effects of two well-known surface chemistries,
      passive PEGylation and active c-RGD peptide conjugation, on in vitro behaviors of
      AgNPs at high temporal and spatial resolution as well as chemical level using
      fluorescence and Raman microscopy. The results show that specific c-RGD peptide
      alphavbeta3 integrin interactions not only induced endosome formation more
      rapidly, enhanced constrained diffusion, but also minimized nonspecific chemical
      interactions between the NPs and intracellular biomolecules than passive
      PEGylation chemistry; as a result, surface enhanced Raman scattering (SERS)
      signals of c-RGD peptides were well resolved inside endosomes in the live cells,
      while Raman signals of PEGylated AgNPs remained unresolvable due to interference
      of surrounding biomolecules, opening up an opportunity to investigate specific
      ligand-receptor interactions in real time at the chemical level. 

PMID- 24559327
TI  - Additive-assisted control over phase-separated nanostructures by manipulating
      alkylthienyl position at donor backbone for solution-processed, non-fullerene,
      all-small-molecule solar cells.
AB  - A non-fullerene, all-small-molecule solar cell (NF-SMSC) device uses the blend of
      a small molecule donor and a small molecule acceptor as the active layer.
      Aggregation ability is a key factor for this type of solar cell. Herein, we used
      the alkylthienyl unit to tune the aggregation ability of the diketopyrrolopyrrole
      (DPP)-based small molecule donors. Replacing two alkoxyl units in BDT-O-DPP with
      two alkylthienyl units yields BDT-T-DPP, and further introducing another two
      alkylthienyl units into the backbone produces BDT-T-2T-DPP. With the introduction
      of alkylthienyl, the backbone becomes twisted. As a result, the pipi-stacking
      strength, aggregation ability, and crystallite size all obey the sequence of BDT
      O-DPP > BDT-T-DPP > BDT-T-2T-DPP. When selected a reported perylene diimide dimer
      of bis-PDI-T-EG as acceptor, the best NF-SMSC device exhibits a power conversion
      efficiency of 1.34, 2.01, and 1.62%, respectively, for the BDT-O-DPP, BDT-T-DPP,
      and BDT-T-2T-DPP based system. The BDT-T-DPP/bis-PDI-T-EG system yields the best
      efficiency of 2.01% among the three combinations. This is due to the moderate
      aggregation ability of BDT-T-DPP yields moderate phase size of 30-50 nm, whereas
      the strong aggregation ability of BDT-O-DPP gives a bigger size of 50-80 nm, and
      the weak aggregation ability of BDT-T-2T-DPP produces a smaller size of 10-30 nm.
      The BDT-T-DPP/bis-PDI-T-EG combination exhibits balanced hole/electron mobility
      of 0.022/0.016 cm(2)/(V s), whereas the BDT-O-DPP/bis-PDI-T-EG and the BDT-T-2T
      DPP/bis-PDI-T-EG blend show a hole/electron mobility of 0.0011/0.0057 cm(2)/(V s)
      and 0.0016/0.11 cm(2)/(V s), respectively. 

PMID- 24559326
TI  - DNA interstrand cross-linking upon irradiation of aryl halide C-nucleotides.
AB  - gamma-Radiolysis kills cells by damaging DNA via radical processes. Many of the
      radical pathways are O2 dependent, which results in a reduction in the
      cytotoxicity of ionizing radiation in hypoxic tumor cells. Consequently, there is
      a need for chemical agents that increase DNA damage by ionizing radiation under
      O2-deficient conditions. Modified nucleotides that are incorporated in DNA and
      produce highly reactive sigma-radicals are useful as radiosensitizing agents.
      Aryl halide C-nucleotides (4-6) were incorporated into oligonucleotides by solid
      phase synthesis. Duplex DNA containing 4-6 forms interstrand cross-links upon
      gamma-radiolysis under anaerobic conditions or UV irradiation. Deep Vent (exo(-))
      DNA polymerase accepted the nucleotide triphosphate of C-nucleotide 6 as a
      substrate and preferentially incorporated it opposite pyrimidines, but no further
      extension was detected. Incorporation of 6 in extended products by Deep Vent
      (exo(-)) during PCR or by Sequenase during copying of single stranded DNA plasmid
      was undetectable. Aryl halide nucleotide analogues that produce DNA interstrand
      cross-links under anaerobic conditions upon irradiation are potentially useful as
      radiosensitizing agents, but further research is needed to identify molecules
      that are incorporated by DNA polymerases and do not block further polymerization
      for this approach to be useful in cells. 

PMID- 24559328
TI  - Veterinary education in a connected world.

PMID- 24559329
TI  - Age affects the adjustment of cognitive control after a conflict: evidence from
      the bivalency effect.
AB  - Age affects cognitive control. When facing a conflict, older adults are less able
      to activate goal-relevant information and inhibit irrelevant information.
      However, cognitive control also affects the events after a conflict. The purpose
      of this study was to determine whether age affects the adjustment of cognitive
      control following a conflict. To this end, we investigated the bivalency effect,
      that is, the performance slowing occurring after the conflict induced by bivalent
      stimuli (i.e., stimuli with features for two tasks). In two experiments, we
      tested young adults (aged 20-30) and older adults (aged 65-85) in a paradigm
      requiring alternations between three tasks, with bivalent stimuli occasionally
      occurring on one task. The young adults showed a slowing for all trials following
      bivalent stimuli. This indicates a widespread and long-lasting bivalency effect,
      replicating previous findings. In contrast, the older adults showed a more
      specific and shorter-lived slowing. Thus, age affects the adjustment of cognitive
      control following a conflict. 

PMID- 24559330
TI  - The unusual self-organization of dialkyldithiophosphinic acid self-assembled
      monolayers on ultrasmooth gold.
AB  - We report the formation and characterization of self-assembled monolayers (SAMs)
      of dialkyldithiophosphinic acid adsorbates [CH3(CH2)n]2P(S)SH (R2DTPA) (n = 5, 9,
      11, 13, 15) on ultrasmooth gold substrates prepared by the template stripping
      method. The SAMs were characterized using X-ray photoelectron spectroscopy,
      reflection-absorption infrared spectroscopy, contact angle measurements, lateral
      force microscopy, and electrochemical impedance spectroscopy. The data show these
      SAMs exhibit an unusual trend in alkyl chain crystallinity; SAMs formed from
      adsorbates with short alkyl chains (n = 5) are ordered and crystalline, and the
      alkyl groups become increasingly disordered and liquidlike as the number of
      methylene units is increased. This trend is the opposite of the typical behavior
      exhibited by n-alkanethiolate SAMs, in which the alkyl layer becomes more
      crystalline and ordered as the alkyl chain length is increased. We discuss four
      factors that operate together to determine how R2DTPA self-organize within SAMs
      on TS gold: (i) adsorbate-substrate interactions; (ii) gold substrate morphology;
      (iii) lateral van der Waals interactions between alkyl groups; and (iv) steric
      demands of the alkyl groups. We also present a model for the structures of these
      SAMs on the basis of consideration of the data and the structural parameters of a
      model (n)Bu2DTPA adsorbate. In this model, interdigitation of short alkyl chains
      stabilizes a trans-extended, crystalline arrangement and produces an ordered
      alkyl layer. As the alkyl chain length is increased, the increased steric demands
      of the alkyl groups lead to liquidlike, disorganized alkyl layers. 

PMID- 24559331
TI  - Communication: the dark singlet state as a doorway state in the ultrafast and
      efficient intersystem crossing dynamics in 2-thiothymine and 2-thiouracil.
AB  - Femtosecond broadband transient absorption experiments are reported for 2
      thiothymine and 2-thiouracil in aqueous buffer solution and in acetonitrile. It
      is shown that the S1(npi*) state acts as a doorway state in the ultrafast and
      efficient population of the T1(pipi*) state upon 316 nm excitation. A sequential
      kinetic model is presented to explain the excited-state dynamics in 2-thiothymine
      and 2-thiouracil upon UVA excitation: S2(pipi*) -> S1(npi*) -> T1(pipi*). The
      experimental results are also used to scrutinize the excited-state relaxation
      pathways recently predicted for 2-thiouracil at the CASPT2//CASSCF level of
      theory [G. Cui and W. Fang, J. Chem. Phys. 138, 044315 (2013)]. The efficient
      population of the T1(pipi*) state for both 2-thiothymine and 2-thiouracil in a
      few hundreds of femtoseconds lends further support to the emerging idea that
      thiobase derivatives exhibit photo-toxic properties that can be effectively
      harnessed in photo-chemotherapeutic applications. 

PMID- 24559332
TI  - Eckart frame vibration-rotation Hamiltonians: contravariant metric tensor.
AB  - Eckart frame is a unique embedding in the theory of molecular vibrations and
      rotations. It is defined by the condition that the Coriolis coupling of the
      reference structure of the molecule is zero for every choice of the shape
      coordinates. It is far from trivial to set up Eckart kinetic energy operators
      (KEOs), when the shape of the molecule is described by curvilinear coordinates.
      In order to obtain the KEO, one needs to set up the corresponding contravariant
      metric tensor. Here, I derive explicitly the Eckart frame rotational measuring
      vectors. Their inner products with themselves give the rotational elements, and
      their inner products with the vibrational measuring vectors (which, in the
      absence of constraints, are the mass-weighted gradients of the shape coordinates)
      give the Coriolis elements of the contravariant metric tensor. The vibrational
      elements are given as the inner products of the vibrational measuring vectors
      with themselves, and these elements do not depend on the choice of the body
      frame. The present approach has the advantage that it does not depend on any
      particular choice of the shape coordinates, but it can be used in conjunction
      with all shape coordinates. Furthermore, it does not involve evaluation of
      covariant metric tensors, chain rules of derivation, or numerical
      differentiation, and it can be easily modified if there are constraints on the
      shape of the molecule. Both the planar and non-planar reference structures are
      accounted for. The present method is particular suitable for numerical work. Its
      computational implementation is outlined in an example, where I discuss how to
      evaluate vibration-rotation energies and eigenfunctions of a general N-atomic
      molecule, the shape of which is described by a set of local polyspherical
      coordinates. 

PMID- 24559333
TI  - Energy transfer between a nanosystem and its host fluid: a multiscale
      factorization approach.
AB  - Energy transfer between a macromolecule or supramolecular assembly and a host
      medium is considered from the perspective of Newton's equations and Lie-Trotter
      factorization. The development starts by demonstrating that the energy of the
      molecule evolves slowly relative to the time scale of atomic collisions
      vibrations. The energy is envisioned to be a coarse-grained variable that
      coevolves with the rapidly fluctuating atomistic degrees of freedom. Lie-Trotter
      factorization is shown to be a natural framework for expressing this coevolution.
      A mathematical formalism and workflow for efficient multiscale simulation of
      energy transfer is presented. Lactoferrin and human papilloma virus capsid-like
      structure are used for validation. 

PMID- 24559334
TI  - Generalizing the self-healing diffusion Monte Carlo approach to finite
      temperature: a path for the optimization of low-energy many-body bases.
AB  - A statistical method is derived for the calculation of thermodynamic properties
      of many-body systems at low temperatures. This method is based on the self
      healing diffusion Monte Carlo method for complex functions [F. A. Reboredo, J.
      Chem. Phys. 136, 204101 (2012)] and some ideas of the correlation function Monte
      Carlo approach [D. M. Ceperley and B. Bernu, J. Chem. Phys. 89, 6316 (1988)]. In
      order to allow the evolution in imaginary time to describe the density matrix, we
      remove the fixed-node restriction using complex antisymmetric guiding wave
      functions. In the process we obtain a parallel algorithm that optimizes a small
      subspace of the many-body Hilbert space to provide maximum overlap with the
      subspace spanned by the lowest-energy eigenstates of a many-body Hamiltonian. We
      show in a model system that the partition function is progressively maximized
      within this subspace. We show that the subspace spanned by the small basis
      systematically converges towards the subspace spanned by the lowest energy
      eigenstates. Possible applications of this method for calculating the
      thermodynamic properties of many-body systems near the ground state are
      discussed. The resulting basis can also be used to accelerate the calculation of
      the ground or excited states with quantum Monte Carlo. 

PMID- 24559335
TI  - Transient quantum coherent response to a partially coherent radiation field.
AB  - The response of an arbitrary closed quantum system to a partially coherent
      electric field is investigated, with a focus on the transient coherences in the
      system. As a model we examine, both perturbatively and numerically, the
      coherences induced in a three level V system. Both rapid turn-on and pulsed turn
      on effects are investigated. The effect of a long and incoherent pulse is also
      considered, demonstrating that during the pulse the system shows a coherent
      response which reduces after the pulse is over. Both the pulsed scenario and the
      thermally broadened CW case approach a mixed state in the long time limit, with
      rates dictated by the adjacent level spacings and the coherence time of the
      light, and via a mechanism that is distinctly different from traditional
      decoherence. These two excitation scenarios are also explored for a minimal "toy"
      model of the electronic levels in pigment protein complex PC645 by both a
      collisionally broadened CW laser and by a noisy pulse, where unexpectedly long
      transient coherence times are observed and explained. The significance of
      environmentally induced decoherence is noted. 

PMID- 24559336
TI  - On the determination of the diagonal components of the optical activity tensor in
      chiral molecules.
AB  - It is shown that the diagonal components of the mixed electric-magnetic dipole
      polarizability tensor, used to rationalize the optical rotatory power of chiral
      molecules, are origin independent, if they are referred to the coordinate system
      defined by the eigenvectors of the dynamic electric dipole polarizability, for a
      given value omega of the frequency of a monochromatic wave impinging on an
      ordered sample. Within this reference frame, the individual diagonal components
      of the mixed electric-magnetic dipole polarizability are separately measurable
      properties. The theoretical method is applied via a test calculation to the
      cyclic 1,2-M enantiomer of the dioxin molecule, using a large Gaussian basis set
      to estimate near Hartree-Fock values within a series of dipole length, velocity,
      and acceleration representations. 

PMID- 24559337
TI  - Water dimer equilibrium constant calculation: a quantum formulation including
      metastable states.
AB  - We present a full quantum evaluation of the water second virial coefficient B(T)
      based on the Takahashi-Imada second order approximation. As the associated trace
      T r[e(-betaH(AB)) - e(-betaH(0)(AB))] is performed in the coordinate
      representation, it does also include contribution from the whole continuum, i.e.,
      resonances and collision pairs of monomers. This approach is compared to a Path
      Integral Monte Carlo evaluation of this coefficient by Schenter [J. Chem. Phys.
      117, 6573 (2002)] for the TIP4P potential and shown to give extremely close
      results in the low temperature range (250-450 K) reported. Using a recent ab
      initio flexible potential for the water dimer, this new formulation leads to very
      good agreement with experimental values over the whole range of temperatures
      available. The virial coefficient is then used in the well known relation Kp(T) =
      -(B(T) - bM)/RT where the excluded volume bM is assimilated to the second virial
      coefficient of pure water monomer vapor and approximated from the inner repulsive
      part of the interaction potential. This definition, which renders bM temperature
      dependent, allows us to retrieve the 38 cm(3) mol(-1) value commonly used, at
      room temperature. The resulting values for Kp(T) are in agreement with available
      experimental data obtained from infrared absorption spectra of water vapor.

PMID- 24559338
TI  - Electrostatic force between a charged sphere and a planar surface: a general
      solution for dielectric materials.
AB  - Using the bispherical coordinate system, an analytical solution describing the
      electrostatic force between a charged dielectric sphere and a planar dielectric
      surface is presented. This new solution exhibits excellent numerical convergence,
      and is sufficiently general as to allow for the presence of charge on both the
      sphere and the surface. The solution has been applied to two examples of sphere
      plane interactions chosen from the literature, namely, (i) a charged lactose
      sphere interacting with a neutral glass surface and (ii) a charged polystyrene
      sphere interacting with a neutral graphite surface. Theory suggests that in both
      cases the electrostatic force makes a major contribution to the experimentally
      observed attraction at short sphere-plane separations, and that the force is much
      longer ranged than previously suggested. 

PMID- 24559339
TI  - Computational efficiency improvement with Wigner rotation technique in studying
      atoms in intense few-cycle circularly polarized pulses.
AB  - We show that by introducing Wigner rotation technique into the solution of time
      dependent Schrodinger equation in length gauge, computational efficiency can be
      greatly improved in describing atoms in intense few-cycle circularly polarized
      laser pulses. The methodology with Wigner rotation technique underlying our
      openMP parallel computational code for circularly polarized laser pulses is
      described. Results of test calculations to investigate the scaling property of
      the computational code with the number of the electronic angular basis function l
      as well as the strong field phenomena are presented and discussed for the
      hydrogen atom. 

PMID- 24559340
TI  - Nudged-elastic band used to find reaction coordinates based on the free energy.
AB  - Transition paths characterize chemical reaction mechanisms. In this paper, we
      present a new method to find mean reaction paths based on the free energy. A
      nudged elastic band (NEB) is optimized using gradients and Hessians of the free
      energy, which are obtained from umbrella integration. The transition state can be
      refined by a Newton-Raphson search starting from the highest point of the NEB
      path. All optimizations are done using Cartesian coordinates. Independent
      molecular dynamics (MD) runs are performed at each image used to discretize the
      path. This makes the method intrinsically parallel. In contrast to other free
      energy methods, the algorithm does not become more expensive when including more
      degrees of freedom in the active space. The method is applied to the alanine
      dipeptide as a test case and compared to pathways that have been derived from
      metadynamics and forward flux sampling. 

PMID- 24559341
TI  - The FADE mass-stat: a technique for inserting or deleting particles in molecular
      dynamics simulations.
AB  - The emergence of new applications of molecular dynamics (MD) simulation calls for
      the development of mass-statting procedures that insert or delete particles on
      the-fly. In this paper we present a new mass-stat which we term FADE, because it
      gradually "fades-in" (inserts) or "fades-out" (deletes) molecules over a short
      relaxation period within a MD simulation. FADE applies a time-weighted relaxation
      to the intermolecular pair forces between the inserting/deleting molecule and any
      neighbouring molecules. The weighting function we propose in this paper is a
      piece-wise polynomial that can be described entirely by two parameters: the
      relaxation time scale and the order of the polynomial. FADE inherently conserves
      overall system momentum independent of the form of the weighting function. We
      demonstrate various simulations of insertions of atomic argon, polyatomic TIP4P
      water, polymer strands, and C60 Buckminsterfullerene molecules. We propose FADE
      parameters and a maximum density variation per insertion-instance that restricts
      spurious potential energy changes entering the system within desired tolerances.
      We also demonstrate in this paper that FADE compares very well to an existing
      insertion algorithm called USHER, in terms of accuracy, insertion rate (in dense
      fluids), and computational efficiency. The USHER algorithm is applicable to
      monatomic and water molecules only, but we demonstrate that FADE can be generally
      applied to various forms and sizes of molecules, such as polymeric molecules of
      long aspect ratio, and spherical carbon fullerenes with hollow interiors. 

PMID- 24559342
TI  - Adaptive sparse grid expansions of the vibrational Hamiltonian.
AB  - The vibrational Hamiltonian involves two high dimensional operators, the kinetic
      energy operator (KEO), and the potential energy surface (PES). Both must be
      approximated for systems involving more than a few atoms. Adaptive approximation
      schemes are not only superior to truncated Taylor or many-body expansions (MBE),
      they also allow for error estimates, and thus operators of predefined precision.
      To this end, modified sparse grids (SG) are developed that can be combined with
      adaptive MBEs. This MBE/SG hybrid approach yields a unified, fully adaptive
      representation of the KEO and the PES. Refinement criteria, based on the
      vibrational self-consistent field (VSCF) and vibrational configuration
      interaction (VCI) methods, are presented. The combination of the adaptive MBE/SG
      approach and the VSCF plus VCI methods yields a black box like procedure to
      compute accurate vibrational spectra. This is demonstrated on a test set of
      molecules, comprising water, formaldehyde, methanimine, and ethylene. The test
      set is first employed to prove convergence for semi-empirical PM3-PESs and
      subsequently to compute accurate vibrational spectra from CCSD(T)-PESs that agree
      well with experimental values. 

PMID- 24559343
TI  - Optimization of the Jastrow factor using the random-phase approximation and a
      similarity-transformed Hamiltonian: application to band-structure calculation for
      some semiconductors and insulators.
AB  - Based on the random-phase approximation and the transcorrelated (TC) method, we
      optimize the Jastrow factor together with one-electron orbitals in the Slater
      determinant in the correlated wave function with a new scheme for periodic
      systems. The TC method is one of the promising wave function theories for first
      principles electronic structure calculation, where the many-body wave function is
      approximated as a product of a Slater determinant and a Jastrow factor, and the
      Hamiltonian is similarity-transformed by the Jastrow factor. Using this
      similarity-transformed Hamiltonian, we can optimize the one-electron orbitals
      without evaluating 3N-dimensional integrations for the N-electron system. In
      contrast, optimization of the Jastrow factor within the framework of the TC
      method is computationally much more expensive and has not been performed for
      solid-state calculations before. In this study, we also benefit from the
      similarity-transformation in optimizing the Jastrow factor. Our optimization
      scheme is tested in applications to some solids from narrow-gap semiconductors to
      wide-gap insulators, and it is verified that the band gap of a wide-gap insulator
      and the lattice constants of some solids are improved by this optimization with
      reasonable computational cost. 

PMID- 24559344
TI  - Coherent superposition of M-states in a single rovibrational level of H2 by Stark
      induced adiabatic Raman passage.
AB  - We prepare an ensemble of isolated rovibrationally excited (v = 1, J = 2) H2
      molecules in a phase-locked superposition of magnetic sublevels M using Stark
      induced adiabatic Raman passage with linearly polarized single-mode pump (at 532
      nm, ~6 ns pulse duration, 200 mJ/pulse) and Stokes (699 nm, ~4 ns pulse duration,
      20 mJ/pulse) laser excitation. A biaxial superposition state, given by
      [line]psi(t)? = 1/?(2)[[line]nu = 1, J = 2, M = -2? - [line]nu = 1, J = 2, M =
      +2?], is prepared with linearly but cross-polarized pump and Stokes laser pulses
      copropagating along the quantization z-axis. The degree of phase coherence is
      measured by using the O(2) line of the H2 E,F-X (0,1) band via 2 + 1 resonance
      enhanced multiphoton ionization (REMPI) at 210.8 nm by recording interference
      fringes in the REMPI signal in a time-of-flight mass spectrometer as the
      direction of the UV laser polarization is rotated using a half-wave plate. Nearly
      60% population transfer from H2 (v = 0, J = 0) ground state to the superposition
      state in H2 (v = 1, J = 2) is measured from the depletion of the Q(0) line of the
      E,F-X (0,0) band as the Stokes frequency is tuned across the (v = 0, J = 0) -> (v
      = 1, J = 2) Raman resonance.

PMID- 24559345
TI  - Thermophysical properties of multi-shock compressed dense argon.
AB  - In contrast to the single shock compression state that can be obtained directly
      via experimental measurements, the multi-shock compression states, however, have
      to be calculated with the aid of theoretical models. In order to determine
      experimentally the multiple shock states, a diagnostic approach with the Doppler
      pins system (DPS) and the pyrometer was used to probe multiple shocks in dense
      argon plasmas. Plasma was generated by a shock reverberation technique. The shock
      was produced using the flyer plate impact accelerated up to ~6.1 km/s by a two
      stage light gas gun and introduced into the plenum argon gas sample, which was
      pre-compressed from the environmental pressure to about 20 MPa. The time-resolved
      optical radiation histories were determined using a multi-wavelength channel
      optical transience radiance pyrometer. Simultaneously, the particle velocity
      profiles of the LiF window was measured with multi-DPS. The states of multi-shock
      compression argon plasma were determined from the measured shock velocities
      combining the particle velocity profiles. We performed the experiments on dense
      argon plasmas to determine the principal Hugonoit up to 21 GPa, the re-shock
      pressure up to 73 GPa, and the maximum measure pressure of the fourth shock up to
      158 GPa. The results are used to validate the existing self-consistent
      variational theory model in the partial ionization region and create new
      theoretical models. 

PMID- 24559346
TI  - Spatial modulation spectroscopy of graphene sheets.
AB  - Two different samples of graphene, multi-layer flakes on Si/SiO2 substrates and
      single layer graphene on glass, have been examined by reflectivity contrast and
      spatial modulation spectroscopy measurements. For the multi-layer graphene
      flakes, the reflectivity contrast and spatial modulation spectroscopy
      measurements are in good agreement, validating the application of spatial
      modulation spectroscopy to two-dimensional samples. The measurements for single
      layer graphene on glass show features that correspond to increases and decreases
      in reflectivity. The features with increased reflectivity are assigned to small
      regions of multilayer graphene or polymer, and the features with decreased
      reflectivity are assigned to holes in the graphene film. Using a model for thin
      film reflectivity we calculate the size dependent spatial modulation signal for
      the holes, and find that a significant number of holes have a larger than
      expected signal. This could arise from the presence of multi-layers of graphene
      in the sample, or because of optical resonance effects for the holes. 

PMID- 24559347
TI  - First principles study of the structural, electronic, and transport properties of
      triarylamine-based nanowires.
AB  - We investigate with state of the art density functional theory the structural,
      electronic, and transport properties of a class of recently synthesized
      nanostructures based on triarylamine derivatives. First, we consider the single
      molecule precursors in the gas phase and calculate their static properties,
      namely (i) the geometrical structure of the neutral and cationic ions, (ii) the
      electronic structure of the frontier molecular orbitals, and (iii) the ionization
      potential, hole extraction potential, and internal reorganization energy. This
      initial study does not evidence any direct correlation between the properties of
      the individual molecules and their tendency to self-assembly. Subsequently, we
      investigate the charge transport characteristics of the triarylamine derivatives
      nanowires, by using Marcus theory. For one derivative we further construct an
      effective Hamiltonian including intermolecular vibrations and evaluate the
      mobility from the Kubo formula implemented with Monte Carlo sampling. These two
      methods, valid respectively in the sequential hopping and polaronic band limit,
      give us values for the room-temperature mobility in the range 0.1-12 cm(2)/Vs.
      Such estimate confirms the superior transport properties of triarylamine-based
      nanowires, and make them an attracting materials platform for organic
      electronics. 

PMID- 24559348
TI  - Laboratory transferability of optimally shaped laser pulses for quantum control.
AB  - Optimal control experiments can readily identify effective shaped laser pulses,
      or "photonic reagents," that achieve a wide variety of objectives. An important
      additional practical desire is for photonic reagent prescriptions to produce
      good, if not optimal, objective yields when transferred to a different system or
      laboratory. Building on general experience in chemistry, the hope is that
      transferred photonic reagent prescriptions may remain functional even though all
      features of a shaped pulse profile at the sample typically cannot be reproduced
      exactly. As a specific example, we assess the potential for transferring optimal
      photonic reagents for the objective of optimizing a ratio of photoproduct ions
      from a family of halomethanes through three related experiments. First, applying
      the same set of photonic reagents with systematically varying second- and third
      order chirp on both laser systems generated similar shapes of the associated
      control landscape (i.e., relation between the objective yield and the variables
      describing the photonic reagents). Second, optimal photonic reagents obtained
      from the first laser system were found to still produce near optimal yields on
      the second laser system. Third, transferring a collection of photonic reagents
      optimized on the first laser system to the second laser system reproduced
      systematic trends in photoproduct yields upon interaction with the homologous
      chemical family. These three transfers of photonic reagents are demonstrated to
      be successful upon paying reasonable attention to overall laser system
      characteristics. The ability to transfer photonic reagents from one laser system
      to another is analogous to well-established utilitarian operating procedures with
      traditional chemical reagents. The practical implications of the present results
      for experimental quantum control are discussed. 

PMID- 24559349
TI  - Properties of liquid clusters in large-scale molecular dynamics nucleation
      simulations.
AB  - We have performed large-scale Lennard-Jones molecular dynamics simulations of
      homogeneous vapor-to-liquid nucleation, with 10(9) atoms. This large number
      allows us to resolve extremely low nucleation rates, and also provides excellent
      statistics for cluster properties over a wide range of cluster sizes. The
      nucleation rates, cluster growth rates, and size distributions are presented in
      Diemand et al. [J. Chem. Phys. 139, 74309 (2013)], while this paper analyses the
      properties of the clusters. We explore the cluster temperatures, density
      profiles, potential energies, and shapes. A thorough understanding of the
      properties of the clusters is crucial to the formulation of nucleation models.
      Significant latent heat is retained by stable clusters, by as much as DeltakT =
      0.1epsilon for clusters with size i = 100. We find that the clusters deviate
      remarkably from spherical-with ellipsoidal axis ratios for critical cluster sizes
      typically within b/c = 0.7 +/- 0.05 and a/c = 0.5 +/- 0.05. We examine cluster
      spin angular momentum, and find that it plays a negligible role in the cluster
      dynamics. The interfaces of large, stable clusters are thinner than planar
      equilibrium interfaces by 10%-30%. At the critical cluster size, the cluster
      central densities are between 5% and 30% lower than the bulk liquid expectations.
      These lower densities imply larger-than-expected surface areas, which increase
      the energy cost to form a surface, which lowers nucleation rates. 

PMID- 24559350
TI  - Electronic properties of graphene nano-flakes: energy gap, permanent dipole,
      termination effect, and Raman spectroscopy.
AB  - The electronic properties of graphene nano-flakes (GNFs) with different edge
      passivation are investigated by using density functional theory. Passivation with
      F and H atoms is considered: C(N(c)) X(N(x)) (X = F or H). We studied GNFs with
      10 < Nc < 56 and limit ourselves to the lowest energy configurations. We found
      that: (i) the energy difference Delta between the highest occupied molecular
      orbital and the lowest unoccupied molecular orbital decreases with Nc, (ii)
      topological defects (pentagon and heptagon) break the symmetry of the GNFs and
      enhance the electric polarization, (iii) the mutual interaction of bilayer GNFs
      can be understood by dipole-dipole interaction which were found sensitive to the
      relative orientation of the GNFs, (iv) the permanent dipoles depend on the edge
      terminated atom, while the energy gap is independent of it, and (v) the presence
      of heptagon and pentagon defects in the GNFs results in the largest difference
      between the energy of the spin-up and spin-down electrons which is larger for the
      H-passivated GNFs as compared to F-passivated GNFs. Our study shows clearly the
      effect of geometry, size, termination, and bilayer on the electronic properties
      of small GNFs. This study reveals important features of graphene nano-flakes
      which can be detected using Raman spectroscopy.

PMID- 24559351
TI  - Melting temperatures of H2O up to 72 GPa measured in a diamond anvil cell using
      CO2 laser heating technique.
AB  - The melting curve of H2O from 49 to 72 GPa was determined by using a laser-heated
      diamond anvil cell. Double-sided CO2 laser heating technique was employed in
      order to heat the sample directly. Discontinuous changes of the heating
      efficiency attributed to the H2O melting were observed between 49 and 72 GPa. The
      obtained melting temperatures at 49 and 72 GPa are 1200 and 1410 K, respectively.
      We found that the slope of the melting curve significantly decreases with
      increasing pressure, only 5 K/GPa at 72 GPa while 44 K/GPa at 49 GPa. Our results
      suggest that the melting curve does not intersect with the isentropes of Uranus
      and Neptune, and hence, H2O should remain in the liquid state even at the
      pressure and temperature conditions found deep within Uranus and Neptune. 

PMID- 24559352
TI  - Phase behavior and dynamics of a cholesteric liquid crystal.
AB  - The synthesis, equation of state, phase diagram, and dielectric relaxation
      properties are reported for a new liquid crystal, 4(')-butyl-4-(2
      methylbutoxy)azoxybenzene (4ABO5*), which exhibits a cholesteric phase at ambient
      temperature. The steepness of the intermolecular potential was characterized from
      the thermodynamic potential parameter, Gamma = 4.3 +/- 0.1 and the dynamic
      scaling exponent, gamma = 3.5 +/- 0.2. The difference between them is similar to
      that seen previously for nematic and smectic liquid crystals, with the near
      equivalence of Gamma and gamma consistent with the near constancy of the
      relaxation time of 4ABO5* at the cholesteric to isotropic phase transition (i.e.,
      the clearing line). Thus, chirality does not cause deviations from the general
      relationship between thermodynamics and dynamics in the ordered phase of liquid
      crystals. The ionic conductivity of 4ABO5* shows strong coupling to the
      reorientational dynamics. 

PMID- 24559353
TI  - Quadrupole terms in the Maxwell equations: Born energy, partial molar volume, and
      entropy of ions.
AB  - A new equation of state relating the macroscopic quadrupole moment density Q to
      the gradient of the field ?E in an isotropic fluid is derived: Q = alphaQ(?E -
      U?.E/3), where the quadrupolarizability alphaQ is proportional to the squared
      molecular quadrupole moment. Using this equation of state, a generalized
      expression for the Born energy of an ion dissolved in quadrupolar solvent is
      obtained. It turns out that the potential and the energy of a point charge in a
      quadrupolar medium are finite. From the obtained Born energy, the partial molar
      volume and the partial molar entropy of a dissolved ion follow. Both are compared
      to experimental data for a large number of simple ions in aqueous solutions. From
      the comparison the value of the quadrupolar length LQ is determined, LQ =
      (alphaQ/3E)(1/2) = 1-4 A. Data for ion transfer from aqueous to polar oil
      solution are analyzed, which allowed for the determination of the
      quadrupolarizability of nitrobenzene.

PMID- 24559354
TI  - Enhancement of surface phonon modes in the Raman spectrum of ZnSe nanoparticles
      on adsorption of 4-mercaptopyridine.
AB  - By chemically etching a thin film of crystalline ZnSe with acid, we observe a
      strong Raman enhancement of the surface phonon modes of ZnSe on adsorption of a
      molecule (4-mercaptopyridine). The surface is composed of oblate hemi-ellipsoids,
      which has a large surface-to-bulk ratio. The assignment of the observed modes (at
      248 and 492 cm(-1)) to a fundamental and first overtone of the surface optical
      mode is consistent with observations from high-resolution electron energy loss
      spectroscopy as well as calculations. 

PMID- 24559355
TI  - Electronic structure of antifluorite Cu2X (X = S, Se, Te) within the modified
      Becke-Johnson potential plus an on-site Coulomb U.
AB  - The traditional photon absorbers Cu2-xX (X = S, Se, and Te) have regained
      significant research attention in the search of earth-abundant photovoltaic
      materials. These moderate- and narrow-gap materials have also been shown to
      exhibit excellent thermoelectric properties recently. However, semimetallic band
      structures with inverted band orderings are predicted for antifluorite structure
      Cu2X using density functional theory with the local density approximation or the
      generalized gradient approximation. We find that semiconducting band structures
      and normal band orderings can be obtained using the modified Becke-Johnson
      potential plus an on-site Coulomb U (the mBJ+U approach), which is consistent
      with our earlier finding for diamond-like Cu-based multinary semiconductors [Y.
      Zhang, J. Zhang, W. Gao, T. A. Abtew, Y. Wang, P. Zhang, and W. Zhang, J. Chem.
      Phys. 139, 184706 (2013)]. The trend of the chemical bonding of Cu2X is analyzed,
      which shows that the positions of the valence band maximum and conduction band
      minimum are strongly affected by the inter-site pd and intra-site sp
      hybridizations, respectively. The calculated gaps of Cu2S and Cu2Se still seem to
      be underestimated compared with experimental results. We also discuss the effects
      of different structural phases and Cu disordering and deficiency on the bandgaps
      of these materials. 

PMID- 24559356
TI  - Toward tuning the surface functionalization of small ceria nanoparticles.
AB  - Understanding and controlling the performance of ceria nanoparticle (CNP)
      catalysts requires knowledge of the detailed structure and property of CNP
      surfaces and any attached functional groups. Here we report thermogravimetric
      analysis results showing that hydrothermally synthesized ~30 nm CNPs are
      decorated with 12.9 hydroxyl groups per nm(2) of CNP surface. Quantum mechanical
      calculations of the density and distribution of bound surface groups imply a
      scaling relationship for surface group density that balances formal charges in
      the functionalized CNP system. Computational results for CNPs with only hydroxyl
      surface groups yield a predicted density of bound hydroxyl groups for ~30 nm CNPs
      that is ~33% higher than measured densities. Quantitative agreement between
      predicted and measured hydroxyl surface densities is achieved when calculations
      consider CNPs with both -OH and -Ox surface groups. For this more general
      treatment of CNP surface functionalizations, quantum mechanical calculations
      predict a range of stable surface group configurations that depend on the
      chemical potentials of O and H, and demonstrate the potential to tune CNP surface
      functionalizations by varying temperature and/or partial pressures of O2 and H2O.

PMID- 24559357
TI  - Degenerate Ising model for atomistic simulation of crystal-melt interfaces.
AB  - One of the simplest microscopic models for a thermally driven first-order phase
      transition is an Ising-type lattice system with nearest-neighbour interactions,
      an external field, and a degeneracy parameter. The underlying lattice and the
      interaction coupling constant control the anisotropic energy of the phase
      boundary, the field strength represents the bulk latent heat, and the degeneracy
      quantifies the difference in communal entropy between the two phases. We simulate
      the (stochastic) evolution of this minimal model by applying rejection-free
      canonical and microcanonical Monte Carlo algorithms, and we obtain caloric curves
      and heat capacity plots for square (2D) and face-centred cubic (3D) lattices with
      periodic boundary conditions. Since the model admits precise adjustment of bulk
      latent heat and communal entropy, neither of which affect the interface
      properties, we are able to tune the crystal nucleation barriers at a fixed degree
      of undercooling and verify a dimension-dependent scaling expected from classical
      nucleation theory. We also analyse the equilibrium crystal-melt coexistence in
      the microcanonical ensemble, where we detect negative heat capacities and find
      that this phenomenon is more pronounced when the interface is the dominant
      contributor to the total entropy. The negative branch of the heat capacity
      appears smooth only when the equilibrium interface-area-to-volume ratio is not
      constant but varies smoothly with the excitation energy. Finally, we simulate
      microcanonical crystal nucleation and subsequent relaxation to an equilibrium
      Wulff shape, demonstrating the model's utility in tracking crystal-melt
      interfaces at the atomistic level. 

PMID- 24559358
TI  - Oxygen diffusion and reactivity at low temperature on bare amorphous olivine-type
      silicate.
AB  - The mobility of O atoms at very low temperatures is not generally taken into
      account, despite O diffusion would add to a series of processes leading to the
      observed rich molecular diversity in space. We present a study of the mobility
      and reactivity of O atoms on an amorphous silicate surface. Our results are in
      the form of reflection absorption infrared spectroscopy and temperature
      programmed desorption spectra of O2 and O3 produced via two pathways: O + O and
      O2 + O, investigated in a submonolayer regime and in the range of temperature
      between 6.5 and 30 K. All the experiments show that ozone is formed efficiently
      on silicate at any surface temperature between 6.5 and 30 K. The derived upper
      limit for the activation barriers of O + O and O2 + O reactions is ~150 K/kb.
      Ozone formation at low temperatures indicates that fast diffusion of O atoms is
      at play even at 6.5 K. Through a series of rate equations included in our model,
      we also address the reaction mechanisms and show that neither the Eley-Rideal nor
      the hot atom mechanisms alone can explain the experimental values. The rate of
      diffusion of O atoms, based on modeling results, is much higher than the one
      generally expected, and the diffusive process proceeds via the Langmuir
      Hinshelwood mechanism enhanced by tunnelling. In fact, quantum effects turn out
      to be a key factor that cannot be neglected in our simulations. Astrophysically,
      efficient O3 formation on interstellar dust grains would imply the presence of
      huge reservoirs of oxygen atoms. Since O3 is a reservoir of elementary oxygen,
      and also of OH via its hydrogenation, it could explain the observed concomitance
      of CO2 and H2O in the ices. 

PMID- 24559359
TI  - Phase equilibrium in argon films stabilized by homogeneous surfaces and
      thermodynamics of two-stage melting transition.
AB  - Freezing of gases adsorbed on open surfaces (e.g., graphite) and in narrow pores
      is a widespread phenomenon which is a subject of a large number of publications.
      Modeling of the gas/liquid-solid transition is usually accomplished with a
      molecular simulation technique. However, quantitative analysis of the gas/liquid
      solid coexistence and thermodynamic properties of the solid layer still
      encounters serious difficulties. This is mainly due to the effect of simulation
      box size on the lattice constant. Since the lattice constant is a function of
      loading and temperature, once the ordering transition has occurred, the
      simulation box size must be corrected in the course of simulation according to
      the Gibbs-Duhem equation. A significant problem is also associated with accurate
      prediction of the two-dimensional liquid-solid coexistence because of a small
      difference in densities of coexisting phases. The aim of this study is
      thermodynamic analysis of the two-dimensional phase coexistence in systems
      involving crystal-like free of defects layers in narrow slit pores. A special
      attention was paid to the determination of triple point temperatures. It is shown
      that intrinsic properties of argon monolayer adsorbed on the graphite surface are
      similar to those of isolated monolayer accommodated in the slit pore having width
      of two argon collision diameters. Analysis of the latter system is shown to be
      clearer and less time-consuming than the former one, which has allowed for
      explanation of the experimentally observed two-stage melting transition of argon
      monolayer on graphite without invoking the periodic surface potential modulation
      and orientational transition. 

PMID- 24559360
TI  - Molecular dynamics analysis of multiphase interfaces based on in situ extraction
      of the pressure distribution of a liquid droplet on a solid surface.
AB  - Molecular dynamics simulations of a nanoscale liquid droplet on a solid surface
      are carried out in order to examine the pressure tensor field around the
      multiphase interfaces, and to explore the validity of Young's equation. By
      applying the virial theorem to a hemicylindrical droplet consisting of argon
      molecules on a solid surface, two-dimensional distribution of the pressure tensor
      is obtained. Tensile principal pressure tangential to the interface is observed
      around the liquid-vapor transition layer, while both tensile and compressive
      principal pressure tangential to the interface exists around the solid-liquid
      transition layer due to the inhomogeneous density distribution. The two features
      intermix inside the overlap region between the transition layers at the contact
      line. The contact angle is evaluated by using a contour line of the maximum
      principal pressure difference. The interfacial tensions are calculated by using
      Bakker's equation and Young-Laplace equation to the pressure tensor distribution.
      The relation between measured contact angle and calculated interfacial tensions
      turns out to be consistent with Young's equation, which is known as the
      description of the force balance at the three-phase interface. 

PMID- 24559361
TI  - Initial decomposition mechanism for the energy release from electronically
      excited energetic materials: FOX-7 (1,1-diamino-2,2-dinitroethene, C2H4N4O4).
AB  - Decomposition of the energetic material FOX-7 (1,1-diamino-2,2-dinitroethylene,
      C2H4N4O4) is investigated both theoretically and experimentally. The NO molecule
      is observed as an initial decomposition product subsequent to electronic
      excitation. The observed NO product is rotationally cold (<35 K) and
      vibrationally hot (2800 K). The initial decomposition mechanism is explored at
      the complete active space self-consistent field (CASSCF) level. Potential energy
      surface calculations at the CASSCF(12,8)/6-31G(d) level illustrate that conical
      intersections play an essential role in the decomposition mechanism.
      Electronically excited S2 FOX-7 can radiationlessly relax to lower electronic
      states through (S2/S1)CI and (S1/S0)CI conical intersections and undergo a nitro
      nitrite isomerization to generate NO product on the S0 state. The theoretically
      predicted mechanism is consistent with the experimental results. As FOX-7
      decomposes on the ground electronic state, thus, the vibrational energy of the NO
      product from FOX-7 is high. The observed rotational energy distribution for NO is
      consistent with the final transition state structure on the S0 state. Ground
      state FOX-7 decomposition agrees with previous work: the nitro-nitrite
      isomerization has the lowest average energy barrier, the C-NH2 bond cleavage is
      unlikely under the given excitation conditions, and HONO formation on the ground
      state surface is energy accessible but not the main process. 

PMID- 24559362
TI  - Direct observation of adsorption geometry for the van der Waals adsorption of a
      single pi-conjugated hydrocarbon molecule on Au(111).
AB  - Weak van der Waals adsorption of pi-conjugated hydrocarbon molecules onto the
      gold surface, Au(111), is one of the essential processes in constructing organic
      metal interfaces in organic electronics. Here we provide a first direct
      observation of adsorption geometry of a single pi-conjugated hydrocarbon molecule
      on Au(111) using an atomically resolved scanning tunneling microscopy study
      combined with van der Waals density functional methodology. For the purpose, we
      utilized a highly symmetric pi-conjugated hydrocarbon molecule,
      dehydrobenzo[12]annulene (DBA), which has a definite three-fold symmetry, the
      same as the Au(111) surface. Interestingly, our observations on an atomically
      resolved scale clearly indicate that the DBA molecule has only one adsorption
      configuration on Au(111) in spite of the weak van der Waals adsorption system.
      Based on the precisely determined adsorption geometry of DBA/Au(111), our
      calculation results imply that even a very small contribution of the interfacial
      orbital interaction at the organic-metal interface can play a decisive role in
      constraining the adsorption geometry even in the van der Waals adsorption system
      of a pi-conjugated hydrocarbon molecule on the noblest Au(111) surface. Our
      observations provide not only deeper insight into the weak adsorption process,
      but also new perspectives to organic electronics using pi-conjugated hydrocarbon
      molecules on the Au surface. 

PMID- 24559363
TI  - Nanoconfined water under electric field at constant chemical potential undergoes
      electrostriction.
AB  - Electric control of nanopore permeation by water and solutions enables gating in
      membrane ion channels and can be exploited for transient surface tuning of rugged
      substrates, to regulate capillary permeability in nanofluidics, and to facilitate
      energy absorption in porous hydrophobic media. Studies of capillary effects,
      enhanced by miniaturization, present experimental challenges in the nanoscale
      regime thus making molecular simulations an important complement to direct
      measurement. In a molecular dynamics (MD) simulation, exchange of water between
      the pores and environment requires modeling of coexisting confined and bulk
      phases, with confined water under the field maintaining equilibrium with the
      unperturbed environment. In the present article, we discuss viable methodologies
      for MD sampling in the above class of systems, subject to size-constraints and
      uncertainties of the barostat function under confinement and nonuniform-field
      effects. Smooth electric field variation is shown to avoid the inconsistencies of
      MD integration under abruptly varied field and related ambiguities of
      conventional barostatting in a strongly nonuniform interfacial system. When using
      a proper representation of the field at the border region of the confined water,
      we demonstrate a consistent increase in electrostriction as a function of the
      field strength inside the pore open to a field-free aqueous environment. 

PMID- 24559364
TI  - Highly mobile segments in crystalline poly(ethylene oxide)8:NaPF6 electrolytes
      studied by solid-state NMR spectroscopy.
AB  - Two types of high-crystallinity poly(ethylene oxide)/NaPF6 electrolytes with
      ethylene oxide (EO)/Na molar ratios of 8:1 and 6:1, termed as PEO8:NaPF6 and
      PEO6:NaPF6 with Mw = 6000 g mol(-1) were prepared, and their ionic conductivity,
      structure, and segmental motions were investigated and compared. PEO8:NaPF6
      polymer electrolyte exhibits the room-temperature ionic conductivity 7.7 * 10(-7)
      S cm(-1) which is about five times higher than the PEO6:NaPF6. By variable
      temperature measurements of static powder spectra and (1)H spin-lattice
      relaxation time in rotation frame ((1)H T1rho), we demonstrate that crystalline
      segments are more highly mobile in the crystalline PEO8:NaPF6 with higher ionic
      conductivity than in the PEO6:NaPF6 with lower ionic conductivity. The large
      angle reorientation motion of polymer segments in the PEO8:NaPF6 onsets at lower
      temperature (~233 K) with a low activation energy 0.31 eV that is comparable with
      that of the pure PEO crystal. Whereas, the large-angle reorientation motion of
      polymer segments in the PEO6:NaPF6 starts around 313 K with a high activation
      energy of 0.91 eV. As a result of the temperature-enhanced large-angle
      reorientations, the (13)C static powder lineshape changes markedly from a low
      temperature wide pattern with apparent principal values of chemical shift delta33
      < delta22 < delta11 to a high-temperature narrow pattern of uniaxial chemical
      shift anisotropy delta33 > delta22 (delta11). It is suggested that the segmental
      motion in crystalline PEO-salt complex promotes ionic conductivity. 

PMID- 24559365
TI  - Mechanical properties of tetra-PEG gels with supercoiled network structure.
AB  - We investigate the effects of swelling and deswelling on the mechanical
      properties of tetra-polyethylene glycol gels with the precisely tuned
      polymerization degree of network strand (Nc) and polymer volume fraction at
      preparation (phi0) by varying the fraction of interest (phim). The phim
      dependence of the elastic modulus exhibits a crossover at phic due to large
      contraction of the network strands (supercoiling) accompanying deswelling. The
      Obukhov model successfully describes the phim-dependence of the elastic modulus.
      We estimate the fractal dimension of network strands (Df) by analyzing the stress
      elongation relationships at high stretching using Pincus blob concept. In the
      supercoiling region, Df increases with an increase in phim, which suggests that
      the gyration radius of network strands decreases with deswelling in affine
      manner. The extensibility increases with an increase in phim because the
      deswelling reduces the distance between the neighboring junctions. These findings
      will help to understand the structure and formation mechanism of supercoiling. 

PMID- 24559366
TI  - Origins of the two simultaneous mechanisms causing glass transition temperature
      reductions in high molecular weight freestanding polymer films.
AB  - From ellipsometry measurements, Pye and Roth [Phys. Rev. Lett. 107, 235701
      (2011)] presented evidence of the presence of two glass transitions originating
      from two distinctly different and simultaneous mechanisms to reduce the glass
      transition temperature within freestanding polystyrene films with thickness less
      than 70 nm. The upper transition temperature T(u)(g)(h) is higher than the lower
      transition temperature T(l)(g)(h) in the ultrathin films. After comparing their
      data with the findings of others, using the same or different techniques, they
      concluded that new theoretical interpretation is needed to explain the two
      transitions and the different dependences of T(u)(g)(h) and T(l)(g)(h) on film
      thickness and molecular weight. We address the problem based on advance in
      delineating the different viscoelastic mechanisms in the glass-rubber transition
      zone of polymers. Theoretical considerations as well as experiments have shown in
      time-scales immediately following the segmental alpha-relaxation are the sub
      Rouse modes with longer length scale but shorter than that of the Rouse modes.
      The existence of the sub-Rouse modes in various polymers including polystyrene
      has been repeatedly confirmed by experiments. We show that the sub-Rouse modes
      can account for the upper transition and the properties observed. The segmental
      alpha-relaxation is responsible for the lower transition. This is supported by
      the fact that the segmental alpha-relaxation in ultrathin freestanding PS films
      had been observed by dielectric relaxation measurements and photon correlation
      spectroscopy. Utilizing the temperature dependence of the segmental relaxation
      times from these experiments, the glass transition temperature
      T(alpha)(g)associated with the segmental relaxation in the ultrathin film is
      determined. It turns out that T(alpha)(g) is nearly the same as T(l)(g)(h) of the
      lower transition, and hence definitely segmental alpha-relaxation is the
      mechanism for the lower transition. Since it is unlikely that the segmental alpha
      relaxation can give rise to two very different transitions simultaneously, a new
      mechanism for the upper transition is needed, and the sub-Rouse modes provide the
      mechanism.

PMID- 24559367
TI  - Dilute rigid dumbbell suspensions in large-amplitude oscillatory shear flow:
      shear stress response.
AB  - We examine the simplest relevant molecular model for large-amplitude shear (LAOS)
      flow of a polymeric liquid: the suspension of rigid dumbbells in a Newtonian
      solvent. We find explicit analytical expressions for the shear rate amplitude and
      frequency dependences of the first and third harmonics of the alternating shear
      stress response. We include a detailed comparison of these predictions with the
      corresponding results for the simplest relevant continuum model: the corotational
      Maxwell model. We find that the responses of both models are qualitatively
      similar. The rigid dumbbell model relies entirely on the dumbbell orientation to
      explain the viscoelastic response of the polymeric liquid, including the higher
      harmonics in large-amplitude oscillatory shear flow. Our analysis employs the
      general method of Bird and Armstrong ["Time-dependent flows of dilute solutions
      of rodlike macromolecules," J. Chem. Phys. 56, 3680 (1972)] for analyzing the
      behavior of the rigid dumbbell model in any unsteady shear flow. We derive the
      first three terms of the deviation of the orientational distribution function
      from the equilibrium state. Then, after getting the "paren functions," we use
      these for evaluating the shear stress for LAOS flow. We find the shapes of the
      shear stress versus shear rate loops predicted to be reasonable. 

PMID- 24559368
TI  - An optimum approximation of n-point correlation functions of random heterogeneous
      material systems.
AB  - An approximate solution for n-point correlation functions is developed in this
      study. In the approximate solution, weight functions are used to connect subsets
      of (n-1)-point correlation functions to estimate the full set of n-point
      correlation functions. In previous related studies, simple weight functions were
      introduced for the approximation of three and four-point correlation functions.
      In this work, the general framework of the weight functions is extended and
      derived to achieve optimum accuracy for approximate n-point correlation
      functions. Such approximation can be utilized to construct global n-point
      correlation functions for a system when there exist limited information about
      these functions in a subset of space. To verify its accuracy, the new formulation
      is used to approximate numerically three-point correlation functions from the set
      of two-point functions directly evaluated from a virtually generated isotropic
      heterogeneous microstructure representing a particulate composite system.
      Similarly, three-point functions are approximated for an anisotropic glass
      fiber/epoxy composite system and compared to their corresponding reference values
      calculated from an experimental dataset acquired by computational tomography.
      Results from both virtual and experimental studies confirm the accuracy of the
      new approximation. The new formulation can be utilized to attain a more accurate
      approximation to global n-point correlation functions for heterogeneous material
      systems with a hierarchy of length scales. 

PMID- 24559369
TI  - Restricted diffusion of methyl groups in proteins revealed by deuteron NMR:
      manifestation of intra-well dynamics.
AB  - The three-site hops of methyl groups are usually used as an approximation of the
      mechanistic description of motions responsible for the longitudinal NMR
      relaxation. Distinguishing between three-site hops and a more realistic mechanism
      of diffusion in a potential requires extended experimental and computational
      analysis. In order to achieve this goal, in this work the restricted diffusion is
      decomposed into two independent modes, namely, the jumps between potential wells
      and intra-well fluctuations, assuming time scale separation between these modes.
      This approach allows us to explain the rise in the theoretical value of T1
      minimum for the restricted diffusion mechanism compared with the three-site hops
      mechanism via rescaling the three-site hops correlation function by the order
      parameter of intra-well motions. The main result of the paper is that, in
      general, intra-well dynamics can be visible in NMR even in the limit of large
      barrier heights in contrast to the common view that this limit converges to the
      three-site hops mechanism. Based on a previously collected detailed set of
      deuteron NMR relaxation and spectral data in the villin headpiece subdomain
      protein over a wide temperature range of 300-31 K, we are then able to conclude
      that the mechanism of diffusion in the threefold potential is likely to be the
      main source of the dynamics in this system. 

PMID- 24559371
TI  - Properties of ThF(x) from infrared spectra in solid argon and neon with
      supporting electronic structure and thermochemical calculations.
AB  - Laser-ablated Th atoms react with F2 in condensing noble gases to give ThF4 as
      the major product. Weaker higher frequency infrared absorptions at 567.2, 564.8
      (576.1, 573.8) cm(-1), 575.1 (582.7) cm(-1) and 531.0, (537.4) cm(-1) in solid
      argon (neon) are assigned to the ThF, ThF2 and ThF3 molecules based on annealing
      and photolysis behavior and agreement with CCSD(T)/aug-cc-pVTZ vibrational
      frequency calculations. Bands at 528.4 cm(-1) and 460 cm(-1) with higher fluorine
      concentrations are assigned to the penta-coordinated species (ThF3)(F2) and ThF5(
      ). These bands shift to 544.2 and 464 cm(-1) in solid neon. The ThF5 molecule has
      the (ThF3)(F2) Cs structure and is essentially the unique [ThF3(+)][F2(-)] ion
      pair based on charge and spin density calculations. Electron capture by
      (ThF3)(F2) forms the trigonal bipyramidal ThF5(-) anion in a highly exothermic
      process. Extensive structure and frequency calculations were also done for
      thorium oxyfluorides and Th2F4,6,8 dimer species. The calculations provide the
      ionization potentials, electron affinities, fluoride affinities, Th-F bond
      dissociation energies, and the energies to bind F2 and F2(-) to a cluster as well
      as dimerization energies. 

PMID- 24559370
TI  - Sensitivities to parameterization in the size-modified Poisson-Boltzmann
      equation.
AB  - Experimental results have demonstrated that the numbers of counterions
      surrounding nucleic acids differ from those predicted by the nonlinear Poisson
      Boltzmann equation, NLPBE. Some studies have fit these data against the ion size
      in the size-modified Poisson-Boltzmann equation, SMPBE, but the present study
      demonstrates that other parameters, such as the Stern layer thickness and the
      molecular surface definition, can change the number of bound ions by amounts
      comparable to varying the ion size. These parameters will therefore have to be
      fit simultaneously against experimental data. In addition, the data presented
      here demonstrate that the derivative, SK, of the electrostatic binding free
      energy, DeltaGel, with respect to the logarithm of the salt concentration is
      sensitive to these parameters, and experimental measurements of SK could be used
      to parameterize the model. However, although better values for the Stern layer
      thickness and ion size and better molecular surface definitions could improve the
      model's predictions of the numbers of ions around biomolecules and SK, DeltaGel
      itself is more sensitive to parameters, such as the interior dielectric constant,
      which in turn do not significantly affect the distributions of ions around
      biomolecules. Therefore, improved estimates of the ion size and Stern layer
      thickness to use in the SMPBE will not necessarily improve the model's
      predictions of DeltaGel. 

PMID- 24559372
TI  - Surfactant as a critical factor when tuning the hydrophilicity in three
      dimensional polyester-based scaffolds: impact of hydrophilicity on their
      mechanical properties and the cellular response of human osteoblast-like cells.
AB  - In tissue engineering, the hydrophilicity of porous scaffolds is essential and
      influences protein and cell adhesion as well as nutrient diffusion into the
      scaffold. The relative low hydrophilicity of degradable polyesters, which limits
      diffusion of nutrients, is a major drawback in large porous scaffolds of these
      materials when used for bone tissue engineering and repair of critical size
      defects. Designing porous biodegradable polymer scaffolds with improved
      hydrophilicity, while maintaining their mechanical, thermal, and degradation
      properties is therefore of clinical interest. Here, surfactants were used to tune
      the hydrophilicity and material properties. A total of 3-20% (w/w) of surfactant,
      polysorbate 80 (Tween 80), was used as an additive in poly(l-lactide-co-1,5
      dioxepan-2-one) [poly(LLA-co-DXO)] and poly(l-lactide)-co-(epsilon-caprolactone)
      [poly(LLA-co-CL)] scaffolds. A significantly decreased water contact angle was
      recorded for all the blends and the crystallinity, glass transition temperature
      and crystallization temperature were reduced with increased amounts of
      surfactant. Copolymers with the addition of 3% Tween 80 had comparable mechanical
      properties as the pristine copolymers. However, the E-modulus and tensile stress
      of copolymers decreased significantly with the addition of 10 and 20% Tween 80.
      Initial cell response of the material was evaluated by seeding human osteoblast
      like cells (HOB) on the scaffolds. The addition of 3% Tween 80 did not
      significantly influence cell attachment or proliferation, while 20% Tween 80
      significantly inhibited osteoblast proliferation. RT-PCR results showed that 3%
      Tween 80 stimulated mRNA expression of alkaline phosphatase (ALP),
      osteoprotegerin (OPG), and bone morphogenetic protein-2 (BMP-2). 

PMID- 24559373
TI  - Surface pressure isotherm for a monolayer of charged colloidal particles at a
      water/nonpolar-fluid interface: experiment and theoretical model.
AB  - Monolayers from electrically charged micrometer-sized silica particles, spread on
      the air/water interface, are investigated. Because of the electrostatic
      repulsion, the distances between the particles are considerably greater than
      their diameters, i.e., we are dealing with nondensely packed interfacial layers.
      The electrostatic repulsion between the particles occurs through the air phase.
      Surface pressure vs area isotherms were measured by Langmuir trough, and the
      monolayers' morphology was monitored by microscope. The mean area per particle is
      determined by Delaunay triangulation and Voronoi diagrams. In terms of mean area,
      the surface pressure for monolayers from polydisperse and monodisperse particles
      obeys the same law. The experiments show that Pi ? L(-3) at large L, where Pi is
      the surface pressure and L is the mean interparticle distance. A theoretical cell
      model is developed, which predicts not only the aforementioned asymptotic law but
      also the whole Pi(L) dependence. The model presumes a periodic distribution of
      the surface charge density, which induces a corresponding electric field in the
      air phase. Then, the Maxwell pressure tensor of the electric field in the air
      phase is calculated and integrated according to the Bakker's formula to determine
      the surface pressure. Thus, all collective effects from the electrostatic
      interparticle interactions are taken into account as well as the effects from the
      particle finite size. By evaporation of water, the particle monolayers are
      deposited on a solid substrate placed on the bottom of the trough. The
      electrostatic interparticle repulsion is strong enough to withstand the
      attractive lateral capillary immersion forces that are operative during the
      drying of the monolayer on the substrate. The obtained experimental results and
      the developed theoretical model can be useful for prediction and control of the
      properties of nondensely packed interfacial monolayers from charged particles
      that find applications for producing micropatterned surfaces. 

PMID- 24559374
TI  - Increased peripheral and local soluble FGL2 in the recovery of renal ischemia
      reperfusion injury in a porcine kidney auto-transplantation model.
AB  - BACKGROUND: Regulatory T cells (Treg) protect kidney against ischemia reperfusion
      (IR) injury via suppressing innate immunity, but the mechanism has not been fully
      clarified. Soluble fibrinogen-like protein 2 (sFGL2), a novel effector of Treg,
      may affect apoptosis and inflammation. This study investigated the role of sFGL2
      in renal IR injury in a porcine kidney auto-transplantation model. MATERIALS AND
      METHODS: The left kidney was retrieved from mini pigs and infused by University
      of Wisconsin solution into the renal artery with the renal artery and vein
      clamped for 24-h cold storage. After the right nephrectomy, the left kidney was
      auto-transplanted into the right for 2 weeks. 3 pigs were sacrificed at day 2, 5,
      7, 10 and 14 post-transplantation respectively. Collected renal tissues and daily
      blood samples were stored for further analyses. RESULTS: Both serum creatinine
      and blood urea nitrogen were maximized during day 2 to 5 and followed by a
      gradual recovery over 2 weeks. The similar pattern were showed in histological
      damage, myeloperoxidase + cells and apoptosis in the kidney, as well as
      circulating TNF-alpha and IFN-gamma. Serum sFGL2 presented a fluctuating increase
      and reached a peak at day 10. The expression of sFGL2 and its receptor
      FcgammaRIIB as well as Foxp3 and IL-10 in the kidney was notably increased from
      day 5 to 10. CONCLUSION: The increased sFGL2 together with FcgammaRIIB during
      renal recovery after IR injury suggested that sFGL2 might be a potential
      renoprotective mediator involved in the renal self-repairing and remodeling in
      this 2-week porcine auto-transplantation model.

PMID- 24559375
TI  - Oriented thin films of a benzodithiophene covalent organic framework.
AB  - A mesoporous electron-donor covalent organic framework based on a
      benzodithiophene core, BDT-COF, was obtained through condensation of a
      benzodithiophene-containing diboronic acid and hexahydroxytriphenylene (HHTP).
      BDT-COF is a highly porous, crystalline, and thermally stable material, which can
      be handled in air. Highly porous, crystalline oriented thin BDT-COF films were
      synthesized from solution on different polycrystalline surfaces, indicating the
      generality of the synthetic strategy. The favorable orientation, crystallinity,
      porosity, and the growth mode of the thin BDT-COF films were studied by means of
      X-ray diffraction (XRD), 2D grazing incidence diffraction (GID), transmission and
      scanning electron microscopy (TEM, SEM), and krypton sorption. The highly porous
      thin BDT-COF films were infiltrated with soluble fullerene derivatives, such as
      [6,6]-phenyl C61 butyric acid methyl ester (PCBM), to obtain an interpenetrated
      electron-donor/acceptor host-guest system. Light-induced charge transfer from the
      BDT-framework to PCBM acceptor molecules was indicated by efficient
      photoluminescence quenching. Moreover, we monitored the dynamics of
      photogenerated hole-polarons via transient absorption spectroscopy. This work
      represents a combined study of the structural and optical properties of highly
      oriented mesoporous thin COF films serving as host for the generation of periodic
      interpenetrated electron-donor and electron-acceptor systems. 

PMID- 24559377
TI  - Does a dry protein undergo a glass transition?
AB  - Bovine serum albumin (BSA) with extremely low hydration level 0.04, which is
      usually defined as dry, has been investigated in the temperature range between
      200 and 340 K by incoherent inelastic neutron scattering using the neutron time
      of-flight spectrometer FOCUS (PSI, Switzerland). Anomalous temperature behavior
      has been revealed for relaxational and low-frequency vibrational dynamics of BSA
      in the vicinity of 250 K. The mean-square atomic displacement has been shown to
      exhibit a change in the slope of temperature dependence near the same
      temperature. The presented results point out that the glass-like transition
      occurs in the dry protein. 

PMID- 24559376
TI  - Functional modelling of a novel mutation in BBS5.
AB  - BACKGROUND: Bardet-Biedl syndrome (BBS) is an autosomal recessive ciliopathy
      disorder with 18 known causative genes (BBS1-18). The primary clinical features
      are renal abnormalities, rod-cone dystrophy, post-axial polydactyly, learning
      difficulties, obesity and male hypogonadism. RESULTS: We describe the clinical
      phenotype in three Saudi siblings in whom we have identified a novel mutation in
      exon 12 of BBS5 (c.966dupT; p.Ala323CysfsX57). This single nucleotide duplication
      creates a frame shift results in a predicted elongated peptide. Translation
      blocking Morpholino oligonucleotides were used to create zebrafish bbs5
      morphants. Morphants displayed retinal layering defects, abnormal cardiac looping
      and dilated, cystic pronephric ducts with reduced cilia expression. Morphants
      also displayed significantly reduced dextran clearance via the pronephros
      compared to wildtype embryos, suggesting reduced renal function in morphants. The
      eye, kidney and heart defects reported in morphant zebrafish resemble the human
      phenotype of BBS5 mutations. The pathogenicity of the novel BBS5 mutation was
      determined. Mutant mRNA was unable to rescue pleiotropic phenotypes of bbs5
      morphant zebrafish and in cell culture we demonstrate a mislocalisation of mutant
      BBS5 protein which fails to localise discretely with the basal body. CONCLUSIONS:
      We conclude that this novel BBS5 mutation has a deleterious function that
      accounts for the multisystem ciliopathy phenotype seen in affected human
      patients.

PMID- 24559378
TI  - Evaluation of six plant species used traditionally in the treatment and control
      of diabetes mellitus in South Africa using in vitro methods.
AB  - CONTEXT: Numerous plants are used by the local communities of South Africa for
      the treatment and management of type II diabetes. OBJECTIVES: For this study, we
      undertook a survey of the plants sold for the management of diabetes in the town
      of Newcastle, South Africa. Identified plants were subsequently evaluated for
      their in vitro antidiabetic activity. MATERIALS AND METHODS: Plants were
      identified through an interview with a herbalist at the market. Antidiabetic
      activity of extracts of purchased plants was evaluated using in vitro alpha
      amylase and alpha-glucosidase activity, as well as islets of Langerhans excretory
      activity. RESULTS: Senna alexandrina Mill. (Fabaceae), Cymbopogon citrates Stapf.
      (Poaceae), Cucurbita pepo L. (Cucuribitaceae), Nuxia floribunda Benth.
      (Stilbaceae), Hypoxis hemerocallidea Fisch. and Mey (Hypoxidaceae), and
      Cinnamomum cassia Blume (Lauraceae) were identified. The hexane extract of S.
      alexandrina (EC50=0.083 mg/ml), ethyl acetate extract of H. hemerocallidea
      (EC50=0.29 mg/ml), and methanol extracts of Cymbopogon citratus (EC50=0.31 mg/ml)
      and Cinnamomum cassia (EC50=0.12 mg/ml) had the highest alpha-amylase inhibitory
      activity, albeit lower than acarbose (EC50=0.50 mg/ml). All the plants had good
      alpha-glucosidase inhibitory activity (>50%) with the exception of some methanol
      (Cinnamomum cassia, N. floribunda, and Cymbopogon citratus) and acetone extracts
      (Cucurbita pepo and N. floribunda). Only the H. hemerocallidea acetone extract
      had an insulin stimulatory effect (2.5 U/ml at 8 MUg/ml). CONCLUSION: All the
      evaluated plants demonstrated inhibitory activity against the specific GIT enzyme
      systems evaluated. Only H. hemerocallidea had insulin secretory activity, adding
      evidence to the traditional use of these purchased plants in the management of
      the type II diabetic post-prandial hyperglycemia.

PMID- 24559379
TI  - A genome-wide association study demonstrates significant genetic variation for
      fracture risk in Thoroughbred racehorses.
AB  - BACKGROUND: Thoroughbred racehorses are subject to non-traumatic distal limb bone
      fractures that occur during racing and exercise. Susceptibility to fracture may
      be due to underlying disturbances in bone metabolism which have a genetic cause.
      Fracture risk has been shown to be heritable in several species but this study is
      the first genetic analysis of fracture risk in the horse. RESULTS: Fracture cases
      (n = 269) were horses that sustained catastrophic distal limb fractures while
      racing on UK racecourses, necessitating euthanasia. Control horses (n = 253) were
      over 4 years of age, were racing during the same time period as the cases, and
      had no history of fracture at the time the study was carried out. The horses
      sampled were bred for both flat and National Hunt (NH) jump racing. 43,417 SNPs
      were employed to perform a genome-wide association analysis and to estimate the
      proportion of genetic variance attributable to the SNPs on each chromosome using
      restricted maximum likelihood (REML). Significant genetic variation associated
      with fracture risk was found on chromosomes 9, 18, 22 and 31. Three SNPs on
      chromosome 18 (62.05 Mb - 62.15 Mb) and one SNP on chromosome 1 (14.17 Mb)
      reached genome-wide significance (p < 0.05) in a genome-wide association study
      (GWAS). Two of the SNPs on ECA 18 were located in a haplotype block containing
      the gene zinc finger protein 804A (ZNF804A). One haplotype within this block has
      a protective effect (controls at 1.95 times less risk of fracture than cases, p =
      1 * 10(-4)), while a second haplotype increases fracture risk (cases at 3.39
      times higher risk of fracture than controls, p = 0.042). CONCLUSIONS: Fracture
      risk in the Thoroughbred horse is a complex condition with an underlying genetic
      basis. Multiple genomic regions contribute to susceptibility to fracture risk.
      This suggests there is the potential to develop SNP-based estimators for genetic
      risk of fracture in the Thoroughbred racehorse, using methods pioneered in
      livestock genetics such as genomic selection. This information would be useful to
      racehorse breeders and owners, enabling them to reduce the risk of injury in
      their horses.

PMID- 24559380
TI  - Isolated generalized tonic-clonic seizure at high altitude in a young male
      trekker with a positive family history of seizure.

PMID- 24559381
TI  - Differences in functional loss associated with ganglion cell complex thinning
      between patients with glaucoma and postoperative macular hole.
AB  - PURPOSE: To compare the changes in the photopic negative response (PhNR) of the
      focal macular electoretinogram (fmERG) caused by a thinning of the ganglion cell
      complex (GCC) between patients with open angle glaucoma (OAG) and after
      successful macular hole (MH) surgery. METHODS: Twenty-seven eyes of 27 OAG
      patients (OAG group), 28 eyes of 28 MH patients (MH group) and 23 eyes of 23
      normal volunteers (control group) were studied. The OAG patients had early stage
      of glaucoma. The MH patients had been successfully treated with vitrectomy 12
      months earlier. The averaged GCC thickness in the macular area (15 degree in a
      diameter) was measured by SD-OCT. The fmERGs were elicited by a 15 degrees 
      stimulus centered on the fovea. RESULTS: The GCC was significantly thinner in the
      OAG and MH groups than in the control group (p < 0.0001). The PhNR amplitude and
      PhNR/b-wave amplitude ratio were significantly reduced in the OAG group compared
      to the control (p < 0.0001), while no significant reduction of the PhNR amplitude
      was observed in the MH group. The PhNR amplitude and PhNR/b-wave amplitude ratio
      were significantly correlated with the GCC thickness in the OAG group (R(2 )=
      0.741 for the PhNR amplitude, R(2 )= 0.564 for the PhNR/b-wave amplitude ratio, p
      < 0.0001 for both). There were significant differences in the slopes of
      regression lines plotting the GCC thickness and the PhNR amplitude (p < 0.05) or
      the PhNR/b-wave amplitude ratio (p < 0.0005) between the OAG and MH groups.
      CONCLUSIONS: The thinning of the GCC affects the RGC function in the macula area
      differently for patients with OAG and patients after MH closure.

PMID- 24559382
TI  - Behavioural divergence of sympatric Anopheles funestus populations in Burkina
      Faso.
AB  - BACKGROUND: In Burkina Faso, two chromosomal forms of the malaria vector
      Anopheles funestus, Folonzo and Kiribina, are distinguished by contrasting
      frequencies of shared polymorphic chromosomal inversions. Sympatric and
      synchronous populations of Folonzo and Kiribina mate assortatively, as indicated
      by a significant deficit of heterokaryotypes, and genetic associations among
      inversions on independently segregating chromosome arms. The present study aimed
      to assess, by intensive longitudinal sampling, whether sympatric Folonzo and
      Kiribina populations are characterized by behavioural differences in key malaria
      vectorial parameters. METHODS: The study was conducted in two adjacent villages
      near Ouagadougou, in the dry savanna of central Burkina Faso. Mosquito adult
      resting behaviour of both forms was compared based on parallel indoor/outdoor
      collections across six breeding seasons; 8,235 fully karyotyped samples of half
      gravid females were analysed in total. Additionally, indoor/outdoor human biting
      behaviour, host selection, and Plasmodium falciparum sporozoite rate was assessed
      and compared between chromosomal forms. RESULTS: The Kiribina form was
      numerically predominant in the area. However, the Folonzo form was significantly
      over-represented in indoor resting collections and showed stronger post-prandial
      endophily, while Kiribina predominated outdoors. Neither form was statistically
      distinguishable in human biting behaviour, and both were more likely to seek
      human blood meals indoors than outside. The human blood index and sporozoite rate
      were comparably high in both chromosomal forms in indoor collections (>89% and
      >8%, respectively). CONCLUSIONS: Both Kiribina and Folonzo chromosomal forms are
      formidable malaria vectors in Burkina Faso. However, the significantly greater
      tendency for the Kiribina form to rest outdoors despite its pronounced
      anthropophily suggests that uniform exposure of the overall An. funestus
      population to indoor-based vector control tools cannot be expected; Kiribina is
      more likely to evade indoor interventions and escape unharmed outdoors, reducing
      the efficacy of malaria control. Accordingly, more efficient methods to detect
      Kiribina and Folonzo, and a more complete understanding of their distribution and
      behaviour in Africa are advocated.

PMID- 24559383
TI  - Human rhinoviruses and severe respiratory infections: is it possible to identify
      at-risk patients early?
AB  - Molecular methods of viral screening have demonstrated that human rhinoviruses
      (HRVs) are associated with lower respiratory tract infections (LRTIs, including
      bronchiolitis and pneumonia), exacerbations of chronic pulmonary disease and the
      development of asthma. Patients with severe chronic diseases are at greater risk
      of developing major clinical problems when infected by HRVs, particularly if they
      are immunocompromised or have a chronic lung disease. Analysing the
      characteristics of HRVs does not provide any certainty concerning the risk of a
      poor prognosis and, although viremia seems to be associated with an increased
      risk of severe HRV infection, the available data are too scanty to be considered
      conclusive. However, a chest x-ray showing alveolar involvement suggests the
      potentially negative evolution of a bacterial superinfection. There is therefore
      an urgent need for more effective diagnostic, preventive and therapeutic measures
      in order to prevent HRV infection, and identify and treat the patients at highest
      risk. 

PMID- 24559384
TI  - Cellulases without carbohydrate-binding modules in high consistency ethanol
      production process.
AB  - BACKGROUND: Enzymes still comprise a major part of ethanol production costs from
      lignocellulose raw materials. Irreversible binding of enzymes to the residual
      substrate prevents their reuse and no efficient methods for recycling of enzymes
      have so far been presented. Cellulases without a carbohydrate-binding module
      (CBM) have been found to act efficiently at high substrate consistencies and to
      remain non-bound after the hydrolysis. RESULTS: High hydrolysis yields could be
      obtained with thermostable enzymes of Thermoascus aurantiacus containing only two
      main cellulases: cellobiohydrolase I (CBH I), Cel7A and endoglucanase II (EG II),
      Cel5A. The yields were decreased by only about 10% when using these cellulases
      without CBM. A major part of enzymes lacking CBM was non-bound during the most
      active stage of hydrolysis and in spite of this, produced high sugar yields.
      Complementation of the two cellulases lacking CBM with CBH II (CtCel6A) improved
      the hydrolysis. Cellulases without CBM were more sensitive during exposure to
      high ethanol concentration than the enzymes containing CBM. Enzymes lacking CBM
      could be efficiently reused leading to a sugar yield of 90% of that with fresh
      enzymes. The applicability of cellulases without CBM was confirmed under
      industrial ethanol production conditions at high (25% dry matter (DM))
      consistency. CONCLUSIONS: The results clearly show that cellulases without CBM
      can be successfully used in the hydrolysis of lignocellulose at high consistency,
      and that this approach could provide new means for better recyclability of
      enzymes. This paper provides new insight into the efficient action of CBM-lacking
      cellulases. The relationship of binding and action of cellulases without CBM at
      high DM consistency should, however, be studied in more detail.

PMID- 24559385
TI  - Topographical variations of the strain-dependent zonal properties of tibial
      articular cartilage by microscopic MRI.
AB  - The topographical variations of the zonal properties of canine articular
      cartilage over the medial tibia were evaluated as the function of external
      loading by microscopic magnetic resonance imaging (uMRI). T2 and T1 relaxation
      maps and GAG (glycosaminoglycan) images from a total of 70 specimens were
      obtained with and without the mechanical loading at 17.6 um depth resolution. In
      addition, mechanical modulus and water content were measured from the tissue. For
      the bulk without loading, the means of T2 at magic angle (43.6 +/- 8.1 ms),
      absolute thickness (907.6 +/- 187.9 um) and water content (63.3 +/- 9.3%) on the
      meniscus-covered area were significantly lower than the means of T2 at magic
      angle (51.1 +/- 8.5 ms), absolute thickness (1251.6 +/- 218.4 um) and water
      content (73.2 +/- 5.6%) on the meniscus-uncovered area. However GAG (86.0 +/-
      15.3 mg/ml) on the covered area was significantly higher than GAG (70.0 +/- 8.8
      mg/ml) on the uncovered area. Complex relationships were found in the tissue
      properties as the function of external loading. The tissue parameters in the
      superficial zone changed more profoundly than the same properties in the radial
      zone. The tissue parameters in the meniscus-covered areas changed differently
      when comparing with the same parameters in the uncovered areas. This project
      confirms that the load-induced changes in the molecular distribution and
      structure of cartilage are both depth-dependent and topographically distributed.
      Such detailed knowledge of the tibial layer could improve the early detection of
      the subtle softening of the cartilage that will eventually lead to the clinical
      diseases such as osteoarthritis.

PMID- 24559386
TI  - One family cluster of avian influenza A(H7N9) virus infection in Shandong, China.
AB  - BACKGROUND: The first case of human infection with avian influenza A (H7N9) virus
      was identified in March, 2013 and the new H7N9 virus infected 134 patients and
      killed 45 people in China as of September 30, 2013. Family clusters with
      confirmed or suspected the new H7N9 virus infection were previously reported, but
      the family cluster of H7N9 virus infection in Shandong Province was first
      reported. CASE PRESENTATION: A 36-year-old man was admitted to Zaozhuang City
      Hospital with progressive respiratory distress and suspicion of impending acute
      respiratory distress syndrome on April 21. The chest radiography revealed
      bilateral ground-glass opacities and pulmonary lesions. The second case, the
      first case's 4 year old son, was admitted to the same hospital on April 28 with
      fever and multiple patchy shadows in the bilateral lungs. Both of the two cases
      were confirmed to infect with H7N9 virus by the results of real-time reverse
      transcriptase-polymerase-chain reaction (rRT-PCR), virus isolation and serum
      antibody titer. At the same time, one environment samples was detected positive
      for H7N9 virus in the living poultry market in Zaozhuang. The homologous analysis
      of the full genome sequence indicated that both viruses from the patients were
      almost genetically identical. The field epidemiology investigation showed that
      the two cases had no recognized exposure to poultry, but had the exposure to the
      environment. The second case had substantial unprotected close exposure to his
      ill father and developed symptoms seven days after his last contact with his
      father. After surgery, the index case and his son were discharged on May 16 and
      May 6, respectively. 11 close contacts of both patients were identified and
      tested negative both the throat swabs and the serum antibody. CONCLUSION: The
      infection of the index case probably resulted from contact with environmentally
      contaminated material. For the son, the probable infection source was from the
      index case during unprotected exposure, but the possibility from the environment
      or other sources could not be completely ruled out.

PMID- 24559387
TI  - The prevalence of urethral and rectal Mycoplasma genitalium among men who have
      sex with men in China, a cross-sectional study.
AB  - BACKGROUND: Although Mycoplasma genitalium (MG) is a common sexually transmitted
      infection (STI), very little information regarding the prevalence of MG among MSM
      (men who have sex with men) is available in China. The objective of this study
      was to determine the prevalence of MG among MSM in the city of Shenzhen,
      Guangdong Province, China, and to identify the potential risk factors associated
      with MG infection in this population. METHODS: Between January and May 2010, a
      total of 409 MSM were recruited in Shenzhen, Guangdong Province, China. An
      anonymous questionnaire was used to collect information regarding their
      sociological and sexual behaviors. In addition, their first-void urine (FVU)
      samples and rectal swabs were collected for PCR-based MG testing. RESULTS: Among
      the 406 FVU and 405 rectal swab samples were collected from 409 MSM, the overall
      MG prevalence was 8.1% (33/406, 95% CI 5.7%-10.6%), with a FVU positivity of 3.4%
      (95% CI 1.7%-5.4%) and a rectal positivity of 5.4% (95% CI 3.5%-7.7%). Using both
      univariate and multivariable logistic regression analyses, urethral MG infection
      was significantly associated with having more heterosexual behaviors (AOR 7.16,
      95% CI 1.89-27.13), and with having unprotected anal intercourse in the past six
      months (AOR 4.80, 95% CI 1.40-16.47). Rectal MG infection was significantly
      associated with HIV infection based on univariate logistic regression analysis
      (OR = 4.49, 95% CI 1.18-17.12). CONCLUSIONS: In this study, we investigated the
      prevalence of MG infection in the population of interest, as determined from both
      urethral and rectal specimen. We showed that MG was more prevalent in MSM who had
      bisexual behaviors compared to those who engaged only in homosexual behaviors.
      Further work is needed to establish the mode of MG transmission and to identify
      its role in HIV transmission. Meanwhile, more attention should be paid to MG
      infection among MSMs, and especially bisexual MSMs, which might have critical
      implications for effective HIV/STD control in China.

PMID- 24559388
TI  - Aggregation-induced emissive copper(I) complexes for living cell imaging.
AB  - Phosphorescent binuclear copper(I) complexes
      [Cu2(BrphenBr)2(Ph2P(CH2)nPPh2)2](ClO4)2 with different conformations are
      obtained by reaction of [Cu(NCCH3)4]ClO4, 3,8-dibromo-1,10-phenanthroline
      (BrphenBr), and corresponding diphosphine ligands, where n = 1, 4, 5, and 6 in
      complexes Cu-1, Cu-2, Cu-3, and Cu-4, respectively. Complex Cu-4 exhibits both
      the eclipsed and the staggered conformations of 18-membered Cu2C12P4
      metallacycles in a 1:1 ratio in the crystal structure. All complexes are very
      stable to air and moisture in the solid state because of the high level of
      protection of all the Cu(I) centers, N and P atom centers resulting from the
      close contact of BrphenBr and diphosphine ligands, and what is more important is
      that there exist very soft P donors and the chelating effect of aromatic N atoms.
      The ESI-MS result through changing the collision cell energy from 0 to 20 eV
      suggests that the corresponding [Cu2(Ph2P(CH2)nPPh2)2](2+) cations are the
      thermodynamically stable species, while [Cu2(BrphenBr)2(Ph2P(CH2)nPPh2)2](ClO4)2
      are stable products in crystallization kinetics in solutions. All complexes Cu-1
      Cu-4 display good aggregation-induced phosphorescence emission (AIPE) behavior in
      CH2Cl2/hexane mixed solvents, which are suggested to arise from restriction of
      intramolecular rotation. Aggregation-induced emission (AIE) of complexes Cu-1-Cu
      4 in PBS/DMSO (99:1, v:v) is used for living HeLa cell imaging successfully with
      green intracellular emission image. 

PMID- 24559389
TI  - Catalytic enantioselective and divergent total synthesis of (+)-10
      oxocylindrocarpidine, (+)-cylindrocarpidine, (-)-N-acetylcylindrocarpinol, and
      (+)-aspidospermine.
AB  - The catalytic enantioselective and divergent total syntheses of Aspidosperma
      alkaloids (+)-10-oxocylindrocarpidine 7, (+)-cylindrocarpidine 1, (-)-N
      acetylcylindrocarpinol 6, and (+)-aspidospermine 8 have been accomplished in 11
      steps from a common precursor (15) on the basis of a highly concise route. The
      route features three metal-catalyzed reactions, including the key Pd-catalyzed
      decarboxylative asymmetric allylation of carbazolones developed in our
      laboratory. Our syntheses, using a combination of C-H activation,
      enantioselective catalysis, and collective synthesis, represent the first total
      synthesis of 10-oxocylindrocarpidine and the first asymmetric total synthesis of
      cylindrocarpidine and N-acetylcylindrocarpinol. 

PMID- 24559390
TI  - Particulate nature of inhaled zinc oxide nanoparticles determines systemic
      effects and mechanisms of pulmonary inflammation in mice.
AB  - Inhalation of zinc oxide nanoparticles (ZnONP) has potential health impact.
      Because zinc ion may involve in the toxicity of ZnONP, we compared adverse
      effects of inhaled aerosolized ZnONP and zinc nitrate in mice. Aerosolized ZnONP
      and zinc nitrate were well-dispersed in the inhalation chamber. Inhalation of
      0.86 mg/m(3) ZnONP or 1.98 mg/m(3) zinc nitrate for 5 h caused acute inflammation
      mainly at bronchioloalveolar junctions of lungs at 24-h post-exposure. Inhalation
      of ZnONP or zinc nitrate increased metallothionein expression in the epithelial
      cells of brochioloalveolar junction. While the effects on cytokines secretion in
      bronchoalveolar lavage were similar between ZnONP and zinc nitrate, only ZnONP
      increased lactate dehydrogenase activity. However, repeated exposure to 0.86
      mg/m(3) ZnONP 5 h/day for 5 days failed to cause a similar adverse effect. Either
      single or repeated exposure to 0.86 mg/m(3) ZnONP increased activities of
      glutamate oxaloacetate transaminase, glutamate pyruvate transaminase and creatine
      phosphokinase in blood. In contrast, exposure to zinc nitrate had no similar
      systemic effects. In human bronchial epithelial cells, ZnONP-induced interleukin
      8 secretion was partially prevented by co-treatment with the Toll-like receptor 4
      (TLR4) inhibitor. Furthermore, ZnONP-induced pulmonary inflammation was greater
      in wild-type mice than in TLR4-deficent mice. It appears that ZnONP-induced acute
      pulmonary inflammation partially depended on TLR4. In summary, we demonstrated
      the dose-responsive effects for inhalation of ZnONP and zinc nitrate in mice. The
      threshold of cytokines induction for inhalation of ZnONP for 5 h was 0.43
      mg/m(3). The particulate characters of ZnONP might contribute to the systemic
      adverse effects and shall be evaluated for assessing its health impact in humans.

PMID- 24559392
TI  - Oligonucleotides--assembled Au nanorod-assisted cancer photothermal ablation and
      combination chemotherapy with targeted dual-drug delivery of Doxorubicin and
      Cisplatin prodrug.
AB  - External stimuli responsive dual drugs carrier was synthesized with Au nanorods
      (NRs) as the platform. On Au NRs, single stranded DNAs were assembled using 5'
      thiol end. Following this, complementary DNA (cDNA) strands were hybridized. This
      hybridized double stranded DNA facilitated doxorubicin (Dox) intercalation into
      the duplexes. The cDNA designed with the 5' amine functional group assisted to
      tether platinum [Pt(IV)] prodrugs by establishing amide bond with the acid group
      at the axial ligand. The other axial acid group in Pt(IV) prodrugs was conjugated
      with the folic acid (FA) to target folate receptors overexpressed in the cancer
      cells. This targeting vehicle provided remote-controlled delivery of this high
      toxic cargo cocktail at the tumor site, ensuring extra specificity that can avoid
      acute toxicity, where release of Dox and Pt(IV) was achieved upon NIR 808 nm
      diode laser irradiation. The dehybridization set the Dox free to bind the cell
      nucleus and cellular reductants reduced Pt(IV) to yield toxic Pt(II), becoming an
      active drug. The in vitro and in vivo studies revealed that this external
      stimulus responsive combination drug delivery was significantly effective. 

PMID- 24559391
TI  - Patient-derived skeletal dysplasia induced pluripotent stem cells display
      abnormal chondrogenic marker expression and regulation by BMP2 and TGFbeta1.
AB  - Skeletal dysplasias (SDs) are caused by abnormal chondrogenesis during cartilage
      growth plate differentiation. To study early stages of aberrant cartilage
      formation in vitro, we generated the first induced pluripotent stem cells (iPSCs)
      from fibroblasts of an SD patient with a lethal form of metatropic dysplasia,
      caused by a dominant mutation (I604M) in the calcium channel gene TRPV4. When
      micromasses were grown in chondrogenic differentiation conditions and compared
      with control iPSCs, mutant TRPV4-iPSCs showed significantly (P<0.05) decreased
      expression by quantitative real-time polymerase chain reaction of COL2A1 (IIA and
      IIB forms), SOX9, Aggrecan, COL10A1, and RUNX2, all of which are cartilage growth
      plate markers. We found that stimulation with BMP2, but not TGFbeta1, up
      regulated COL2A1 (IIA and IIB) and SOX9 gene expression, only in control iPSCs.
      COL2A1 (Collagen II) expression data were confirmed at the protein level by
      western blot and immunofluorescence microscopy. TRPV4-iPSCs showed only focal
      areas of Alcian blue stain for proteoglycans, while in control iPSCs the stain
      was seen throughout the micromass sample. Similar staining patterns were found in
      neonatal cartilage from control and patient samples. We also found that COL1A1
      (Collagen I), a marker of osteogenic differentiation, was significantly (P<0.05)
      up-regulated at the mRNA level in TRPV4-iPSCs when compared with the control, and
      confirmed at the protein level. Collagen I expression in the TRPV4 model also may
      correlate with abnormal staining patterns seen in patient tissues. This study
      demonstrates that an iPSC model can recapitulate normal chondrogenesis and that
      mutant TRPV4-iPSCs reflect molecular evidence of aberrant chondrogenic
      developmental processes, which could be used to design therapeutic approaches for
      disorders of cartilage. 

PMID- 24559393
TI  - Antinociceptive activity of Syzygium cumini leaves ethanol extract on orofacial
      nociception protocols in rodents.
AB  - CONTEXT: Syzygium cumini (L.) Skeels (Myrtaceae) is a tree with dark purple
      fruits, popularly known as "jambolao" or "jambolan". In folk medicine, this plant
      is used for the treatment of diabetes and inflammatory conditions. OBJECTIVE: We
      investigated the antinociceptive effect of ethanol extract (EE) from S. cumini
      leaves on orofacial nociception. MATERIAL AND METHODS: The antinociceptive
      effects of the EE obtained from the leaves of S. cumini were evaluated in mice
      using formalin- and glutamate-induced orofacial nociception. RESULTS: ESI-MS/MS
      analyses demonstrated that major constituents in the analyzed samples coincided
      with the mass of the phenolic acids and flavonoids. In pharmacological approach,
      pre-treatment with EE (100, 200, or 400 mg/kg, p.o.) significantly reduced
      (p<0.05 or p<0.01) the percentage of paw licks time during phase 2 (43.2, 47.1,
      and 57.4%, respectively) of a formalin pain test when compared to control group
      animals. This effect was prevented by pretreatment with glibenclamide and N(G)
      nitro-l-arginine (l-NOARG). The extract, all doses, also caused a marked
      inhibition (p<0.01 or p<0.001) of glutamate-induced orofacial nociception (38.8,
      51.7, and 54.7%) when compared with the control group. No effect was observed
      with the rota-rod model. CONCLUSIONS: We can suggest that the antinociceptive
      effect of the EE is mediated by peripheral mechanisms, possibly involving KATP
      channels and the nitric oxide pathways. These effects appear to be related to the
      presence of flavonoids compounds, such as quercetin.

PMID- 24559394
TI  - Health inequity in access to bariatric surgery: a protocol for a systematic
      review.
AB  - BACKGROUND: Bariatric surgery is the only weight-loss treatment available that
      results in both sustained weight loss and improvements of obesity-related
      comorbidities. Individuals who meet the eligibility criteria for bariatric
      surgery are generally older, come from racial or ethnic minorities, are
      economically disadvantaged, and have low levels of education. However, the
      population who actually receives bariatric surgery does not reflect the
      individuals who need it the most. The objective is to conduct a systematic review
      of the literature exploring the inequities to the access of bariatric surgery.
      METHODS/DESIGN: EMBASE and Medline databases will be searched for observational
      studies that compared at least one of the PROGRESS-PLUS sociodemographic
      characteristics of patients eligible for bariatric surgery to those who actually
      received the procedure. Articles published in the year 1980 to present with no
      language restrictions will be included. For inclusion, studies must only include
      adults (>=18 years old) who meet National Institutes of Health (NIH) eligibility
      criteria for bariatric surgery defined as having either (1) a body mass index
      (BMI) of 40 kg/m2 or greater; or (2) BMI of 35 kg/m2 or greater with significant
      weight-related comorbidities. Eligible interventions will include malabsorptive,
      restrictive, and mixed bariatric procedures. DISCUSSION: There appears to be
      inequities in access to bariatric surgery. In order to resolve the health
      inequity in the treatment of obesity, a synthesis of the literature is needed to
      explore and identify barriers to accessing bariatric surgery. It is anticipated
      that the results from this systematic review will have important implications for
      advancing solutions to minimize inequities in the utilization of bariatric
      surgery. http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42013004920.

PMID- 24559395
TI  - Building a practice research network: obstacles faced and lessons learned at the
      Center for Collegiate Mental Health.
AB  - OBJECTIVE: The Center for Collegiate Mental Health (CCMH) was created through a
      grass-roots initiative among university and college counseling centers to
      standardize assessment procedures, conduct empirical studies, and advocate
      clinical services. METHOD: At present, CCMH has over 240 college counseling
      center members and oversees a research infrastructure based on these centers'
      routine services, describing approximately 90,000 individual clients annually.
      These data are used to provide clinical tools, which can be useful for ongoing
      clinical services as well as program evaluation, quality assurance, and advocacy
      on behalf of the counseling centers and clients. RESULTS: There have been
      substantial obstacles to overcome, and there remain numerous challenges in day-to
      day operations. This article provides a brief overview of the challenges and
      current solutions. CONCLUSIONS: Large-scale collaborations between researchers
      and practitioners are possible, and some recommendations can be made based on the
      experience of CCMH.

PMID- 24559396
TI  - Dual wavelength electroluminescence from CdSe/CdS tetrapods.
AB  - We fabricated a single active layer quantum dot light-emitting diode device based
      on colloidal CdSe (core)/CdS (arm) tetrapod nanostructures capable of
      simultaneously producing room temperature electroluminesence (EL) peaks at two
      spectrally distinct wavelengths, namely, at ~500 and ~660 nm. This remarkable
      dual EL was found to originate from the CdS arms and CdSe core of the tetrapod
      architecture, which implies that the radiative recombination of injected charge
      carriers can independently take place at spatially distinct regions of the
      tetrapod. In contrast, control experiments employing CdSe-core-seeded CdS
      nanorods showed near-exclusive EL from the CdSe core. Time-resolved spectroscopy
      measurements on tetrapods revealed the presence of hole traps, which facilitated
      the localization and subsequent radiative recombination of excitons in the CdS
      arm regions, whereas excitonic recombination in nanorods took place predominantly
      within the vicinity of the CdSe core. These observations collectively highlight
      the role of morphology in the achievement of light emission from the different
      material components in heterostructured semiconductor nanoparticles, thus showing
      a way in developing a class of materials which are capable of exhibiting
      multiwavelength electroluminescence. 

PMID- 24559397
TI  - National Public Health Week 2014: start here together.

PMID- 24559398
TI  - Temperature-driven adsorption and desorption of proteins at solid-liquid
      interfaces.
AB  - The heat-induced desorption and adsorption of the proteins lysozyme, ribonuclease
      A, bovine serum albumin, and fibronectin at protein layers was investigated in
      two different environments: pure buffer and protein solution. Using two different
      environments allows us to distinguish between thermodynamic and kinetic
      mechanisms in the adsorption process. We observed a desorption in buffer and an
      adsorption in protein solution, depending upon protein properties, such as size,
      stability, and charge. We conclude that the desorption in buffer is mainly
      influenced by the mobility of the proteins at the interface, while the adsorption
      in protein solution is driven by conformational changes and, thereby, a gain in
      entropy. These results are relevant for controlling biofilm formation at solid
      liquid interfaces. 

PMID- 24559399
TI  - Auristatin antibody drug conjugate physical instability and the role of drug
      payload.
AB  - The conjugation of hydrophobic cytotoxic agents such as monomethyl auristatin E
      (MMAE) to the interchain sulfhydryl groups of monoclonal antibodies (Mabs)
      through a protease-labile linker generates a heterogeneous drug load
      distribution. The conjugation process can generate high-drug-load species that
      can affect the physical stability of antibody-drug conjugates (ADCs). In this
      study, the mechanism of physical instability of ADCs was investigated by
      formulating the ADC pool as well as isolated drug load species in high and low
      ionic strength buffers to understand the effect of ionic strength on the
      stability of drug-conjugated Mabs. The results showed that the presence of high
      ionic strength buffer led to time-dependent aggregate and fragment formation of
      ADCs, predominantly ADCs with high-drug-load species under stress conditions. In
      addition, differential scanning calorimetry (DSC) results confirmed that there is
      a direct correlation between thermal unfolding and drug payload and that specific
      changes in the DSC thermogram profiles can be assigned to modifications by MMAE. 

PMID- 24559400
TI  - Polyelectrolyte decomplexation via addition of salt: charge correlation driven
      zipper.
AB  - We report the first atomic scale studies of polyelectrolyte decomplexation. The
      complex between DNA and polylysine is shown to destabilize and spontaneously open
      in a gradual, reversible zipper-like mechanism driven by an increase in solution
      salt concentration. Divalent CaCl2 is significantly more effective than
      monovalent NaCl in destabilizing the complex due to charge correlations and water
      binding capability. The dissociation occurs accompanied by charge reversal in
      which charge correlations and ion binding chemistry play a key role. Our results
      are in agreement with experimental work on complex dissociation but in addition
      show the underlying microstructural correlations driving the behavior. Comparison
      of our full atomic level detail and dynamics results with theoretical works
      describing the PEs as charged, rigid rods reveals that although charge
      correlation involved theories provide qualitatively similar responses,
      considering also specific molecular chemistry and molecular level water
      contributions provides a more complete understanding of PE complex stability and
      dynamics. The findings may facilitate controlled release in gene delivery and
      more in general tuning of PE membrane permeability and mechanical characteristics
      through ionic strength. 

PMID- 24559402
TI  - Improving transcriptome construction in non-model organisms: integrating manual
      and automated gene definition in Emiliania huxleyi.
AB  - BACKGROUND: The advent of Next Generation Sequencing technologies and
      corresponding bioinformatics tools allows the definition of transcriptomes in non
      model organisms. Non-model organisms are of great ecological and biotechnological
      significance, and consequently the understanding of their unique metabolic
      pathways is essential. Several methods that integrate de novo assembly with
      genome-based assembly have been proposed. Yet, there are many open challenges in
      defining genes, particularly where genomes are not available or incomplete.
      Despite the large numbers of transcriptome assemblies that have been performed,
      quality control of the transcript building process, particularly on the protein
      level, is rarely performed if ever. To test and improve the quality of the
      automated transcriptome reconstruction, we used manually defined and curated
      genes, several of them experimentally validated. RESULTS: Several approaches to
      transcript construction were utilized, based on the available data: a draft
      genome, high quality RNAseq reads, and ESTs. In order to maximize the
      contribution of the various data, we integrated methods including de novo and
      genome based assembly, as well as EST clustering. After each step a set of
      manually curated genes was used for quality assessment of the transcripts. The
      interplay between the automated pipeline and the quality control indicated which
      additional processes were required to improve the transcriptome reconstruction.
      We discovered that E. huxleyi has a very high percentage of non-canonical splice
      junctions, and relatively high rates of intron retention, which caused unique
      issues with the currently available tools. While individual tools missed genes
      and artificially joined overlapping transcripts, combining the results of several
      tools improved the completeness and quality considerably. The final collection,
      created from the integration of several quality control and improvement rounds,
      was compared to the manually defined set both on the DNA and protein levels, and
      resulted in an improvement of 20% versus any of the read-based approaches alone.
      CONCLUSIONS: To the best of our knowledge, this is the first time that an
      automated transcript definition is subjected to quality control using manually
      defined and curated genes and thereafter the process is improved. We recommend
      using a set of manually curated genes to troubleshoot transcriptome
      reconstruction.

PMID- 24559401
TI  - Early fibrillin-1 assembly monitored through a modifiable recombinant cell
      approach.
AB  - Fibrillin proteins constitute the backbone of extra-cellular macromolecular
      microfibrils. Mutations in fibrillins cause heritable connective tissue
      disorders, including Marfan syndrome, dominant Weill-Marchesani syndrome, and
      stiff skin syndrome. Fibronectin provides a critical scaffold for microfibril
      assembly in cell culture models. Full length recombinant fibrillin-1 was
      expressed by HEK 293 cells, which deposited the secreted protein in a punctate
      pattern on the cell surface. Cocultured fibroblasts consistently triggered
      assembly of recombinant fibrillin-1, which was dependent on a fibronectin network
      formed by the fibroblasts. Deposition of recombinant fibrillin-1 on fibronectin
      fibers occurred first in discrete packages that subsequently extended along
      fibronectin fibers. Mutant fibrillin-1 harboring either a cysteine 204 to serine
      mutation or a RGD to RGA mutation which prevents integrin binding, did not affect
      fibrillin-1 assembly. In conclusion, we developed a modifiable recombinant full
      length fibrillin-1 assembly system that allows for rapid analysis of critical
      roles in fibrillin assembly and functionality. This system can be used to study
      the contributions of specific residues, domains, or regions of fibrillin-1 to the
      biogenesis and functionality of microfibrils. It provides also a method to
      evaluate disease-causing mutations, and to produce microfibril-containing
      matrices for tissue engineering applications, for example, in designing novel
      vascular grafts or stents. 

PMID- 24559403
TI  - Self-assembling properties of peptides derived from TDP-43 C-terminal fragment.
AB  - Two highly fibrillogenic peptide sequences (MNFGAFSINP and EDLIIKGISV) were
      previously reported in the C-terminal fragment (CTF) of TDP-43 (220-414), a
      protein recently implicated in neuro-degenerative diseases such as amyotrophic
      lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD-U). It was
      observed that the sequences MNFGAFS and EDLIIKG harbor their respective
      fibrillogenic domains. Here, the self-assembling properties of peptides obtained
      by systematic deletion of residues from these two sequences were investigated
      with the help of light scattering, thioflavin T fluorescence, transmission
      electron microscopy, and circular dichroism spectroscopy. It was found that the
      pentapeptide NFGAF and the tetrapeptide DLII are the shortest fibrillogenic
      sequences from MNFGAFS and EDLIIKG, respectively. Structure function studies
      revealed that self-assembly of the peptides is largely governed by hydrophobic
      interactions. Both NFGAF and DLII formed hydrogels based on a complex fibrillar
      network, at relatively low concentrations, and of remarkable strength and
      stability. Of particular interest was DLII, a rare aliphatic tetrapeptide that
      formed a hydrogel at a concentration of 1 mg/mL in less than an hour.
      Interestingly, various other tetrapeptides based on DLII (YLII, KLII, NLII, and
      LIID) also formed hydrogels of comparable physical properties, suggesting that an
      amphipathic peptide design based on the hydrophobic LII motif and a single
      residue polar terminus is highly favorable for hydrogelation. Peptides discovered
      in this study, especially DLII and its variants, are some of the shortest ever
      reported to show such structural and functional features, suggesting that they
      can be useful templates for the design of peptide-based soft materials. 

PMID- 24559404
TI  - Time course variations in the mechanisms by which cerebral oxygen delivery is
      maintained on exposure to hypoxia/altitude.
AB  - Normal cerebral function is dependent upon an adequate and continuous supply of
      oxygen. This study calculated cerebral blood flow based on assessment of the
      right middle cerebral artery (MCA) velocity (MCAVel) and MCA diameter (MCADiam)
      by trans-cranial Doppler and trans-cranial Duplex in normoxia, during acute
      exposure to 12% normobaric hypoxia for up to 6 hours, and after 3 days exposure
      to the equivalent altitude, 4392 m, in nine subjects. Mean (SD) MCAVel increased
      both after 6 hours hypoxia from 76.8 (11.4) to 97.2 (17.4) cms/sec (p<0.001), and
      after 3 days at altitude from 68.1 (7.5) [sea level] to 76.2 (10.2) [4392 m]
      (p=0.015). MCADiam increased from 5.07 (0.6) to 6.1 (0.6) mm (p<0.001) after 6
      hours of 12% hypoxia. Calculated mean MCA blood flow increased after 6 hours of
      12% hypoxia from 5.0 (0.6) mL/sec to 8.9 (1.2) mL/sec, but there was no
      difference between sea level and 4392 m. Calculated mean cerebral oxygen delivery
      increased from 72.4 (14.4) to 107 (20.1) mL/sec (p<0.001) after 6 hours of 12%
      hypoxia and was maintained unchanged at 4392 m. An increase in MCA caliber,
      rather than blood velocity, was a major contributor to increased oxygen delivery
      accompanying within the first few hours of exposure to acute hypoxia. During more
      long-term exposure, increases in MCA velocity and a rise in hemoglobin appeared
      to be the more important mechanisms in maintaining cerebral oxygen delivery. The
      implication of this observed change in MCA diameter questions the widely held
      assumption that MCA velocity is a surrogate for flow during acute hypoxic
      exposure.

PMID- 24559406
TI  - Stereoacuity as an indicator of prism adaptation.
AB  - PURPOSE: The purpose of this study was to determine whether stereoacuity can be
      used as an indicator of prism adaptation. In particular, we wanted to know
      whether the time required for stereoacuity to return to the initial level after
      viewing through a prism can be used to determine the degree of adaptation.
      MATERIALS AND METHODS: Eighteen subjects participated in this study. Stereoacuity
      and dissociated phoria were determined using the TNO stereotest and the Maddox
      rod, respectively. Prism vergences were measured using a prism bar. For each
      participant, prism power equivalent to the blur point of base-in (BI) and base
      out (BO) fusional vergence at 40 cm was divided and placed in front of both eyes.
      At 0, 3, 6, 9 and 12 min after prism introduction, the stereoacuity was measured,
      and at 0 and 12 min, the heterophoria was measured. RESULTS: The repeated
      measures ANOVA showed a significant difference between the mean stereoacuity for
      BI and BO prisms at the different measurement times (p < 0.05). For BO prism, the
      initial value was different between 0 and 3 min after the prism introduction,
      whereas for BI prism, a difference in stereoacuity was found between the pre
      prism value and the value at 0, 3 and 6 min. The size of the heterophoria with BO
      and BI prisms was different from 0 to 12 min (p < 0.05). CONCLUSION: The time
      required for stereoacuity to return to baseline level was more than 3 min for BO,
      and more than 6 min for BI prism. In addition, the time required to return to
      baseline values was not similar for the stereoacuity and heterophoria. The
      recovery of stereoacuity is slower when adapting to divergence, as when looking
      from near to far. This implies that stereopsis responds faster to near targets
      than to distant one, and may precede complete phoria adaptation.

PMID- 24559407
TI  - Mode manipulation and near-THz absorptions in binary grating-graphene layer
      structures.
AB  - The excitation and absorption properties of grating coupled graphene surface
      plasmons were studied. It was found that whether a mode can be excited is mainly
      determined by the frequency of incident light and the duty ratio of gratings. In
      the structure consisting graphene bilayer, a blueshift of the excitation
      frequency existed when the distance between neighbor graphene layer were
      decreased gradually. In graphene-grating multilayer structures, a strong
      absorption (approximately 90% at maximum) was found in near-THz range. 

PMID- 24559408
TI  - Microarray analysis revealed markedly differential miRNA expression profiles in
      cervical intraepithelial neoplasias and invasive squamous cell carcinoma.
AB  - AIMS: To investigate the alterations in miRNA expression during the progression
      of dysplasia in cervical epithelium. METHODS: A global miRNA expression profile
      of normal cervical squamous epithelium (Normal), cervical intraepithelial
      neoplasia (CIN) 3 and invasive squamous cell carcinoma (ISCC) was produced using
      the seventh generation of the miRCURYTM LNA microRNA Array (Exiqon, Vedbaek,
      Denmark). The reliability of miRNA arrays was verified by reverse transcription
      PCR. RESULTS: Normal, CIN 3 and ISCC showed distinct miRNA expression profiles.
      The differentially expressed miRNAs in ISCC versus CIN 3 clearly differed from
      that in CIN 3 versus Normal. Compared with ISCC versus Normal, more identical
      miRNAs were found in ISCC versus CIN 3 than in CIN 3 versus Normal. CONCLUSION: A
      particular set of miRNAs was associated with the progression of normal cervical
      epithelium to CIN 3 and CIN 3 to ISCC. The miRNA profile changed more noticeably
      in the progression of CIN to ISCC than normal cervical epithelium to CIN.

PMID- 24559409
TI  - Community-based health insurance programmes and the National Health Insurance
      Scheme of Nigeria: challenges to uptake and integration.
AB  - BACKGROUND: Nigeria has included a regulated community-based health insurance
      (CBHI) model within its National Health Insurance Scheme (NHIS). Uptake to date
      has been disappointing, however. The aim of this study is to review the present
      status of CBHI in SSA in general to highlight the issues that affect its
      successful integration within the NHIS of Nigeria and more widely in developing
      countries. METHODS: A literature survey using PubMed and EconLit was carried out
      to identify and review studies that report factors affecting implementation of
      CBHI in SSA with a focus on Nigeria. RESULTS: CBHI schemes with a variety of
      designs have been introduced across SSA but with generally disappointing results
      so far. Two exceptions are Ghana and Rwanda, both of which have introduced
      schemes with effective government control and support coupled with intensive
      implementation programmes. Poor support for CBHI is repeatedly linked elsewhere
      with failure to engage and account for the 'real world' needs of beneficiaries,
      lack of clear legislative and regulatory frameworks, inadequate financial
      support, and unrealistic enrolment requirements. Nigeria's CBHI-type schemes for
      the informal sectors of its NHIS have been set up under an appropriate
      legislative framework, but work is needed to eliminate regressive financing, to
      involve scheme members in the setting up and management of programmes, to inform
      and educate more effectively, to eliminate lack of confidence in the schemes, and
      to address inequity in provision. Targeted subsidies should also be considered.
      CONCLUSIONS: Disappointing uptake of CBHI-type NHIS elements in Nigeria can be
      addressed through closer integration of informal and formal programmes under the
      NHIS umbrella, with increasing involvement of beneficiaries in scheme design and
      management, improved communication and education, and targeted financial
      assistance.

PMID- 24559410
TI  - The dynamic character of the BCL2 promoter i-motif provides a mechanism for
      modulation of gene expression by compounds that bind selectively to the
      alternative DNA hairpin structure.
AB  - It is generally accepted that DNA predominantly exists in duplex form in cells.
      However, under torsional stress imposed by active transcription, DNA can assume
      nonduplex structures. The BCL2 promoter region forms two different secondary DNA
      structures on opposite strands called the G-quadruplex and the i-motif. The i
      motif is a highly dynamic structure that exists in equilibrium with a flexible
      hairpin species. Here we identify a pregnanol derivative and a class of
      piperidine derivatives that differentially modulate gene expression by
      stabilizing either the i-motif or the flexible hairpin species. Stabilization of
      the i-motif structure results in significant upregulation of the BCL2 gene and
      associated protein expression; in contrast, stabilization of the flexible hairpin
      species lowers BCL2 levels. The BCL2 levels reduced by the hairpin-binding
      compound led to chemosensitization to etoposide in both in vitro and in vivo
      models. Furthermore, we show antagonism between the two classes of compounds in
      solution and in cells. For the first time, our results demonstrate the principle
      of small molecule targeting of i-motif structures in vitro and in vivo to
      modulate gene expression. 

PMID- 24559411
TI  - Case report: passive transfer of hepatitis B antibodies from intravenous
      immunoglobulin.
AB  - BACKGROUND: Prior to initiating immunosuppressive therapy in the treatment of
      autoimmune inflammatory conditions, it is a requirement to screen for certain
      viral serology, including hepatitis B (HBV). A positive result may indicate the
      need for antiviral therapy, or contraindicate immunosuppression all together. An
      accurate interpretation of serological markers is therefore imperative in order
      to treat patients appropriately. We present a case of passive anti-HBV antibody
      transfer following intravenous immunoglobulin (IVIg) infusion, in which
      misinterpretation of serology results almost led to inappropriate treatment with
      antiviral therapy and the withholding of immunosuppressive agents. This
      phenomenon has been previously reported, but awareness remains limited. CASE
      PRESENTATION: A 50 year old Caucasian gentleman with a history of allogeneic
      haematopoietic stem cell transplant for transformed follicular lymphoma was
      admitted to hospital with recurrent respiratory tract infections. Investigation
      found him to be hypogammaglobulinaemic, and he was thus given 1 g/kg of
      intravenous immunoglobulin. The patient also disclosed a 3-week history of
      painful, swollen joints, leading to a diagnosis of seronegative inflammatory
      polyarthritis. Prior to initiating long term immunosuppression, viral screening
      found hepatitis B serology suggestive of past infection, with positive results
      for both anti-HBc and anti-HBs antibody, but negative HBV DNA. In response,
      prednisolone was weaned and the local hepatology team recommended commencement of
      lamivudine. Having been unable to identify a source of infection, the case was
      reported to the local blood centre, who tested a remaining vial from the same
      batch of IVIg and found it to be anti-HBc and anti-HBs positive. Fortunately the
      blood products were identified and tested prior to the patient initiating HBV
      treatment, and the effect of a delay in starting disease-modifying therapy was
      inconsequential in light of an excellent response to first-line therapies.
      CONCLUSION: Misinterpretation of serology results following IVIg infusion may
      lead to significant patient harm, including unnecessary antiviral administration,
      the withholding of treatments, and psychosocial damage. This is especially
      pertinent at a time when we have an ever increasing number of patients being
      treated with IVIg for a wide array of immune-mediated disease. Passive antibody
      transfer should be considered wherever unexpected serological changes are
      identified.

PMID- 24559412
TI  - Current challenges and future perspectives for patient safety in surgery.

PMID- 24559413
TI  - Theoretical insights into the mechanism of olefin elimination in the methanol-to
      olefin process over HZSM-5, HMOR, HBEA, and HMCM-22 zeolites.
AB  - The mechanism of olefin elimination in the process of methanol-to-olefins (MTO)
      over a series of zeolites like HZSM-5, HMOR, HBEA, and HMCM-22 was investigated
      by DFT-D calculations, which is a crucial step that controls the MTO product
      distribution. The results demonstrate that the manners of olefin elimination are
      related to the pore structure of zeolite catalyst and the interaction between
      proton transfer reagent (water or methanol) and zeolite acidic framework. The
      indirect spiro mechanism is preferable to the direct mechanism over HMOR, HBEA,
      and HMCM-22 zeolites with large pores, as suggested by the energy barrier of rate
      determining step and the potential energy surface (PES), but is unfavorable over
      HZSM-5 with medium-sized pores due to the steric hindrance of spiro
      intermediates. Over various zeolites, water and methanol perform differently in
      proton transfer to form the spiro intermediates; over HMOR and HBEA with strong
      acidity, water is superior to methanol in promoting propene elimination, whereas
      over HMCM-22 with relatively weaker acidity, methanol is more favorable as a
      proton transfer reagent. 

PMID- 24559414
TI  - Community awareness of stroke in Accra, Ghana.
AB  - BACKGROUND: Community awareness of stroke, especially the risk factors and
      warning signs is important in the control of the disease. In sub-Saharan Africa,
      little is known about community awareness of stroke though the brunt of stroke is
      currently borne in this region. The aim of the study was to evaluate stroke
      awareness in Accra (capital city of Ghana) particularly, the risk factors and
      warning signs. METHODS: This was a cross-sectional study involving systematic
      sampling of 63 households in each of the 11 sub metropolitan areas of Accra. A
      structured questionnaire was used to collect stroke awareness data from
      respondents randomly sampled in the selected households. Logistic regression
      analyses were done to identify predictors of the main outcome variables including
      recognition of stroke risk factors, stroke warning signs and the organ affected
      by stroke. RESULTS: Only 40% (n = 277) of the 693 respondents correctly
      identified the brain as the organ affected in stroke. Similarly, less than half
      of the respondents could recognize any of the established stroke risk factors as
      well as any of the established stroke warning signs. Over 70% (n > 485) of the
      respondents either believed that stroke is a preventable disease, or lifestyle
      alterations can be made to reduce the risk of stroke, or stroke requires
      emergency treatment. In multivariate analysis, predictors of stroke awareness
      were: age <50 years (OR = 0.56, CI = 0.35-0.92, p = 0.021), presence of a stroke
      risk factor (OR = 2.37, CI = 1.52-3.71, p < 0.001) and Christian Religion (OR =
      14.86, CI = 1.37-161.01, p = 0.03). CONCLUSION: Though stroke is perceived as a
      serious and preventable disease in Accra, community awareness of the risk factors
      and warning signs is sub-optimal. This indicates that community-based education
      programs to increase public awareness of stroke could contribute to decreasing
      the risk of stroke and to increasing the speed of hospital presentation after
      stroke onset.

PMID- 24559416
TI  - International Standards for Neurological Classification of Spinal Cord Injury:
      cases with classification challenges.
AB  - The International Standards for the Neurological Classification of Spinal Cord
      Injury (ISNCSCI) is routinely used to determine the levels of injury and to
      classify the severity of the injury. Questions are often posed to the
      International Standards Committee of the American Spinal Injury Association
      regarding the classification. The committee felt that disseminating some of the
      challenging questions posed, as well as the responses, would be of benefit for
      professionals utilizing the ISNCSCI. Case scenarios that were submitted to the
      committee are presented with the responses as well as the thought processes
      considered by the committee members. The importance of this documentation is to
      clarify some points as well as update the SCI community regarding possible
      revisions that will be needed in the future based upon some rules that require
      clarification. 

PMID- 24559417
TI  - Short Form health surveys and related variants in spinal cord injury research: a
      systematic review.
AB  - CONTEXT: 'Short Form' health surveys - such as the SF-36 and SF-12 - are widely
      used in medical research. Spinal cord injury (SCI) is no exception, despite oft
      cited concerns regarding measurement properties for populations with physical
      impairment. OBJECTIVE: To provide a comprehensive overview of the use of Short
      Form health surveys and their variants within the SCI literature. METHODS: Papers
      published between database inception and September 2012 were identified from 11
      electronic databases; a supplementary reference list search was also conducted.
      Data extraction focused on details regarding the range of different Short Form
      surveys and variants used in SCI research, the respective frequency of use, the
      nature of reporting (complete versus partial reporting) and the method of survey
      administration. RESULTS: One hundred seventy-four papers were identified. Thirty
      six-item Short Form health surveys were frequently administered as complete
      instruments (n = 82); in 69 of these 82 studies (84%), it was not clearly stated
      which 36-item version had been used (e.g. SF-36v1, SF-36v2, RAND-36). Data for
      individual items and domains were often reported (29% of identified studies),
      indicating significant partial use of standardized measures. Modified variants of
      standardized health surveys were administered in 12 studies. CONCLUSION: Although
      standardized Short Form health surveys are common within SCI research, attempts
      to add, delete, or modify items have resulted in a number of variants, often with
      minimal supportive psychometric evidence. Using established, generic outcome
      measures is appealing for a number of reasons. However, validity is paramount and
      requires further explicit consideration within the SCI research community.

PMID- 24559418
TI  - Upper cervical injuries - a rational approach to guide surgical management.
AB  - CONTEXT: The complex anatomy and the importance of ligaments in providing
      stability at the upper cervical spine region (O-C1-C2) require the use of many
      imaging modalities to evaluate upper cervical injuries (UCI). While separate
      classifications have been developed for distinct injuries, a more practical
      treatment algorithm can be derived from the injury pattern in UCI. OBJECTIVE: To
      propose a practical treatment algorithm to guide treatment based on injuries
      characteristic of UCI. METHODS: A literature review was performed on the Pubmed
      database using the following keywords: (1) "occipital condyle injury"; (2)
      "craniocervical dislocation or atlanto-occipital dislocation or craniocervical
      dislocation"; (3) "atlas fractures"; and (4) "axis fractures". Just articles
      containing the diagnosis, classification, and treatment of specific UCI were
      included. The data obtained were analyzed by the authors, dividing the UCI into
      two groups: Group 1 - patients with clear ligamentous injury and Group 2 -
      patients with fractures without ligament disruption. RESULTS: Injuries with
      ligamentous disruption, suggesting surgical treatment, include: atlanto-occipital
      dislocation, mid-substance transverse ligament injury, and C1-2 and C2-3
      ligamentous injuries. In contrast, condyle, atlas, and axis fractures without
      significant displacement/misalignment can be initially treated using external
      orthoses. Odontoid fractures with risk factors for non-union are an exception in
      Group 2 once they are better treated surgically. Patients with neurological
      deficits may have more unstable injuries. CONCLUSIONS: Ascertaining the status of
      relevant ligamentous structures, fracture patterns and alignment are important in
      determining surgical compared with non-surgical treatment for patients with UCI.

PMID- 24559419
TI  - Cardiac arrhythmias the first month after acute traumatic spinal cord injury.
AB  - OBJECTIVE: Cardiovascular complications including cardiac arrest and arrhythmias
      remain a clinical challenge in the management of acute traumatic spinal cord
      injury (SCI). Still, there is a lack of knowledge regarding the characteristics
      of arrhythmias in patients with acute traumatic SCI. The aim of this prospective
      observational study was to investigate the occurrence of cardiac arrhythmias and
      cardiac arrests in patients with acute traumatic SCI. METHODS: As early as
      possible after SCI 24-hour Holter monitoring was performed. Additional Holter
      recordings were performed 1, 2, 3, and 4 weeks after SCI. Furthermore, 12-lead
      electrocardiograms (ECGs) were obtained shortly after SCI and at 4 weeks.
      RESULTS: Thirty patients were included. Bradycardia (heart rate (HR) <50 b.p.m.)
      was present in 17-35% of the patients with cervical (C1-C8) SCI (n = 24) within
      the first 14 days. In the following 14 days, the occurrence was 22-32%.
      Bradycardia in the thoracic (Th1-Th12) SCI group (n = 6) was present in 17-33%
      during the observation period. The differences between the two groups were not
      statistically significant. The mean minimum HR was significantly lower in the
      cervical group compared with the thoracic group both on 12-lead ECGs obtained
      shortly after SCI (P = 0.030) and at 4 weeks (P = 0.041). CONCLUSION: Many
      patients with cervical SCI experience arrhythmias such as bradycardia, sinus node
      arrest, supraventricular tachycardia, and more rarely cardiac arrest the first
      month after SCI. Apart from sinus node arrests and limited bradycardia, no
      arrhythmias were seen in patients with thoracic SCI. Standard 12-lead ECGs will
      often miss the high prevalence these arrhythmias have.

PMID- 24559420
TI  - Post-traumatic growth following spinal cord injury.
AB  - CONTEXT/OBJECTIVE: Examine the relationship of post-traumatic psychological
      growth (PTG), depression, and personal and injury characteristics in persons with
      spinal cord injury (SCI). DESIGN: Cross-sectional survey. SETTING: Community.
      PARTICIPANTS: Eight hundred and twenty-four adults with SCI. INTERVENTIONS: None.
      OUTCOME MEASURES: Five items from the Post-traumatic Growth Inventory, reflecting
      positive change after injury in life priorities, closeness to others, new
      opportunities being available, stronger faith, and personal strength. RESULTS:
      Initial structural equation model testing of a conceptual model of personal and
      injury characteristics, violent etiology, depression, and PTG resulted in a poor
      fit. Model modifications resulted in an improved fit, but explained only 5% of
      the variance in PTG. Being female, younger, having less formal education, and
      less time since injury had significant relationships with PTG, whereas
      depression, violent etiology, and injury level/severity did not. In each PTG
      domain, between 54 and 79% of the sample reported at least some positive change
      after injury. CONCLUSIONS: The results of this study, while promising, explained
      only a small portion of the variance in PTG. A majority of the sample experienced
      some positive change after injury, with the greatest change in discovering that
      they were stronger than they thought they were. Comparing means previously
      reported in a non-SCI sample of those who experienced trauma, positive change
      after injury was comparable for each PTG item except for new opportunities being
      available, which was significantly lower for those with SCI. Future directions of
      research include the development of theoretical models of PTG after SCI.

PMID- 24559421
TI  - Spinal cord injury facts and figures at a glance.

PMID- 24559422
TI  - Linear free-energy relationship and rate study on a silylation-based kinetic
      resolution: mechanistic insights.
AB  - The substituent effect of different p-substituted triphenylsilyl chlorides on
      silylation-based kinetic resolutions was explored. Electron-donating groups slow
      down the reaction rate and improve the selectivity, while electron-withdrawing
      groups increase the reaction rate and decrease the selectivity. Linear free
      energy relationships were found correlating both selectivity factors and initial
      rates to the sigma(para) Hammett parameters. A weak correlation of selectivity
      factors to Charton values was also observed when just alkyl substituents were
      employed but was nonexistent when substituents with more electronic effects were
      incorporated. The rate data suggest that a significant redistribution of charge
      occurs in the transition state, with an overall decrease in positive charge. The
      linear free-energy relationship derived from selectivity factors is best
      understood by the Hammond postulate. Early and late transition states describe
      the amount of substrate participation in the transition state and therefore the
      difference in energy between the diastereomeric transition states of the two
      enantiomers. This work highlights our efforts toward understanding the mechanism
      and origin of selectivity in our silylation-based kinetic resolution.

PMID- 24559423
TI  - Nitrogen-doped graphene nanoribbons as efficient metal-free electrocatalysts for
      oxygen reduction.
AB  - Nitrogen-doped graphene nanoribbon (N-GNR) nanomaterials with different nitrogen
      contents have been facilely prepared via high temperature pyrolysis of graphene
      nanoribbons (GNR)/polyaniline (PANI) composites. Here, the GNRs with excellent
      surface integration were prepared by longitudinally unzipping the multiwalled
      carbon nanotubes. With a high length-to-width ratio, the GNR sheets are prone to
      form a conductive network by connecting end-to-end to facilitate the transfer of
      electrons. Different amounts of PANI acting as a N source were deposited on the
      surface of GNRs via a layer-by-layer approach, resulting in the formation of N
      GNR nanomaterials with different N contents after being pyrolyzed.
      Electrochemical characterizations reveal that the obtained N8.3-GNR nanomaterial
      has excellent catalytic activity toward an oxygen reduction reaction (ORR) in an
      alkaline electrolyte, including large kinetic-limiting current density and long
      term stability as well as a desirable four-electron pathway for the formation of
      water. These superior properties make the N-GNR nanomaterials a promising kind of
      cathode catalyst for alkaline fuel cell applications. 

PMID- 24559424
TI  - Chloride ion-aided self-assembly of pseudoclathrochelate metal tris
      pyrazoloximates.
AB  - Chloride ion-aided one-pot template self-assembly of a mixed pyrazoloxime ligand
      with phenylboronic acid on a corresponding metal(II) ion as a matrix afforded the
      first boron-capped zinc, cobalt, iron, and manganese pseudoclathrochelate tris
      pyrazoloximates. The presence of a pseudocross-linking hydrogen-bonded chloride
      ion is critical for their formation, as the same chloride-capped complexes were
      isolated even in the presence of large excesses of bromide and iodide ions. As
      revealed by X-ray diffraction, all complexes are capped with a chloride ion via
      three N-H...Cl hydrogen bonds that stabilize their pseudomacrobicyclic
      frameworks. The MN6 coordination polyhedra possess a distorted trigonal prismatic
      geometry, with the distortion angles phi between their nonequivalent N3 bases of
      approximately 0 degrees . Temperature dependences of the effective magnetic
      moment for the paramagnetic complexes showed the encapsulated metal(II) ions to
      be in a high-spin state in the temperature range of 2-300 K. In the case of the
      iron(II) pseudoclathrochelate, density functional theory (DFT) and time-dependent
      DFT calculations were used to assess its spin state as well as the (57)Fe
      Mossbauer and UV-vis-NIR parameters. Cyclic voltammetry studies performed for
      these pseudomacrobicyclic complexes showed them to undergo irreversible or quasi
      reversible metal-localized oxidations and reductions. As no changes are observed
      in the presence of a substantial excess of bromide ion, no anion-exchange
      reaction occurs, and thus the pseudoclathrochelates have a high affinity toward
      chloride anions in solution. 

PMID- 24559425
TI  - Timing of tuberculosis transmission and the impact of household contact tracing.
      An agent-based simulation model.
AB  - RATIONALE: Household contact tracing has recently been endorsed for global
      tuberculosis (TB) control, but its potential population-level impact remains
      uncertain. OBJECTIVES: To project the maximum impact of household contact tracing
      for TB in a moderate-burden setting. METHODS: We developed a stochastic, agent
      based simulation model of a simplified TB epidemic, calibrated to a setting of
      moderate TB incidence. We used data from the literature to generate "community
      driven" and "household-driven" scenarios in which 22 and 50% of TB transmission
      occurred within the household, respectively. In each scenario, we simulated an
      intervention in which the household members are screened and treated for TB at
      the time of an index patient's active TB diagnosis. MEASUREMENTS AND MAIN
      RESULTS: By the time of TB diagnosis, 75 to 95% of initial household infections
      had already occurred, but only 1.5 to 3.0% of contacts had sufficient time to
      progress to active TB. With 100% sensitive tracing of all contacts for 5
      consecutive years, TB incidence declined by 10 to 15%, with a mean year-over-year
      decline of 2% per year. Effects were sustained for many years after stopping the
      intervention. Providing preventive therapy with contact tracing nearly doubled
      this impact (17-27% decline in incidence). Impact was proportional to sensitivity
      and coverage; thus, if 50% of contacts were screened with a 50% sensitive test,
      TB incidence declined by only 0.5% per year. CONCLUSIONS: Household contact
      tracing is unlikely to transform TB epidemiology in isolation but has the
      potential, especially with provision of preventive therapy, to augment a
      comprehensive package of interventions that could substantially reduce the
      population-level burden of TB.

PMID- 24559426
TI  - Visualizing atomistic formation process of SrOx thin films on SrTiO3.
AB  - Metallic conductivity observed in the heterostructure of LaAlO3/SrTiO3 has
      attracted great attention, triggering a debate over whether the origin is an
      intrinsic electronic effect or a defect-related phenomenon. One of the issues to
      be solved is the role of SrO layer, which turns the conductive interface into an
      insulator when inserted between LaAlO3 and SrTiO3. To understand the origins of
      this oxide interface phenomenon and to further explore unconventional
      functionalities, it is necessary to elucidate how SrO layers are formed during
      the initial growth process at the atomic level. Here, we atomically resolve
      growth processes of heteroepitaxial SrOx films on SrTiO3(001)-(?13*?13)-R33.7
      degrees  substrate using scanning tunneling microscopy/spectroscopy. On the sub
      unit-cell SrOx film surface, no periodic structure was observed as a result of
      random Ti incorporation into the SrOx islands, indicating the importance of the
      control of excess Ti atoms on the substrate prior to deposition. This random
      arrangement of Ti atoms is a marked contrast to the homoepitaxy on SrTiO3(001)
      (?13*?13)-R33.7 degrees . Furthermore, the formation of SrOx islands introduced
      defects in the surrounding SrTiO3 substrate surface. Such atom-by-atom
      engineering and characterizations of oxide heterostructures not only provide
      microscopic understanding of formation process of interfaces in metal-oxides, but
      also would lead to the creation of exotic electronic phenomena and novel
      functionalities at these interfaces.

PMID- 24559427
TI  - Self-assembly of amphiphilic peptide (AF)6H5K15 derivatives: roles of hydrophilic
      and hydrophobic residues.
AB  - A molecular dynamics simulation study is reported to investigate the roles of
      hydrophilic and hydrophobic residues in the self-assembly of (AF)6H5K15 peptide
      derivatives. The peptide, as well as water and counterions, are represented by
      the MARTINI coarse-grained model. The assembly is observed to follow a three-step
      process: formation of small clusters, large clusters, and micelles. With
      increasing length of hydrophilic Lys residues in (AF)6H5Kn (n = 10, 15, 20, and
      25), assembly capability is found to be reduced with the formation of smaller
      micelles or the presence of individual peptide chains. Upon replacing Ala by more
      hydrophobic Phe in AmFnH5K15 (m + n = 12), larger micelles are formed. With
      increasing length of hydrophobic Phe residues in FnH5K15 (n = 4, 8, 12, and 16),
      micelle size increases and the morphology shifts from spherical to fiber-like.
      The simulation study provides mechanistic insight into the crucial roles of
      hydrophilicity and hydrophobicity in the assembly of (AF)6H5K15 derivatives; it
      reveals that assembly capability is reduced by increasing hydrophilicity, whereas
      increasing hydrophobicity leads to morphology transition. 

PMID- 24559428
TI  - Impact of gold nanoparticles on zebrafish exposed to a spiked sediment.
AB  - Increasing use of metallic nanomaterials is likely to result in release of these
      particles into aquatic environments; nevertheless it is unclear whether these
      materials present a hazard to aquatic organisms. The impact of contaminated
      sediment containing 14-nm gold nanoparticles (AuNPs) was investigated in the
      zebrafish Danio rerio exposed for 20 days to two concentrations, 16 and 55 ug/g
      dry weight. AuNPs were released from the sediment to the water column, and during
      this period the mean concentrations of AuNP in the filtered water fraction were
      0.25 +/- 0.05 and 0.8 +/- 0.1 ug/L, respectively. A similar experiment with ionic
      gold contamination was simultaneously performed to obtain a positive control.
      AuNP exposure triggered various effects in fish tissues including modifications
      of genome composition, shown using a random amplified polymorphic DNA-PCR
      genotoxicity test. Expression of genes involved in oxidative stress,
      mitochondrial metabolism, detoxification and DNA repair were also modulated in
      response to AuNP contamination. Gold altered neurotransmission, since brain
      acetylcholine esterase activity increased for both tested doses of AuNP but not
      for ionic gold. Gold accumulation in fish tissues demonstrated the lower
      bioavailability of AuNP compared to ionic Au, and underlined the higher toxic
      potential of the nanoparticle form. 

PMID- 24559429
TI  - Identification of metalloporphyrins with high sensitivity using graphene-enhanced
      resonance Raman scattering.
AB  - Graphene-enhanced resonance Raman scattering (GERRS) was performed for the
      detection of three different metallo-octaethylporphyrins (M-OEPs; M = 2H, FeCl,
      and Pt) homogeneously thermal vapor deposited on a graphene surface. GERRS of M
      OEPs were measured using three different excitation wavelengths, lambda(ex) =
      405, 532, and 633 nm, and characterized detail vibrational bands for the
      identification of M-OEPs. The GERRS spectra of Pt-OEP at lambda(ex) = 532 nm
      showed ~29 and ~162 times signal enhancement ratio on graphene and on graphene
      with Ag nanoclusters, respectively, compared to the spectra from bare SiO2
      substrate. This enhancement ratio, however, was varied with M-OEPs and excitation
      wavelengths. The characteristic peaks and band shapes of GERRS for each M-OEP
      were measured with high sensitivity (100 pmol of thermal vapor deposited Pt-OEP),
      and these facilitate the selectively recognition of molecules. Also, the peaks
      shift and broadening provide the evidence of the interaction between graphene and
      M-OEPs through the charge transfer and pi-orbital interaction. The increase of
      graphene layer induced the decrease of signal intensity and GERRS effect was
      almost not observed on the thick graphite flakes. Further experiments with
      various substrates demonstrated that the interaction of single layer of graphene
      with molecule is the origin of the Raman signal enhancement of M-OEPs. In this
      experiment, we proved the graphene is a good alternative substrate of Raman
      spectroscopy for the selective detection of various metalloporphyrins with high
      sensitivity.

PMID- 24559430
TI  - Checking whether there is an increased risk of post-transplant
      lymphoproliferative disorder and other cancers with specific modern
      immunosuppression regimens in renal transplantation: protocol for a network meta
      analysis of randomized and observational studies.
AB  - BACKGROUND: Patients undergoing renal transplant procedures require multi-agent
      immunosuppressive regimens both short term (induction phase) and long term
      (maintenance phase) to minimize the risk of organ rejection. There are several
      drug classes and agents for immunosuppression. Use of these agents may increase
      the risk of different harms including not only infections, but also malignancies
      including post-transplant lymphoproliferative disorder. There is a need to
      identify which regimens minimize the risk of such outcomes. The objective of this
      systematic review and network meta-analysis of randomized and observational
      studies is to explore whether certain modern regimens of immunosuppression used
      to prevent organ rejection in renal transplant patients are associated with an
      increased risk of post-transplant lymphoproliferative disorder and other
      malignancies. METHODS/DESIGN: 'Modern' regimens were defined to be those
      evaluated in controlled studies beginning in 1990 or later. An electronic
      literature search of Medline, Embase and the Cochrane Central Register of
      Controlled Trials has been designed by an experienced information specialist and
      peer reviewed by a second information specialist. Study selection and data
      collection will be performed by two reviewers. The outcomes of interest will
      include post-transplant lymphoproliferative disorder and other incident forms of
      malignancy occurring in adult renal transplant patients. Network meta-analyses of
      data from randomized and observational studies will be performed where judged
      appropriate based on a review of the clinical and methodological features of
      included studies. A sequential approach to meta-analysis will be used to combine
      data from different designs. DISCUSSION: Our systematic review will include both
      single-agent and multi-agent modern pharmacotherapy regimens in patients
      undergoing renal transplantation. It will synthesize malignancy outcomes. Our
      work will also add to the development of methods for network meta-analysis across
      study designs to assess treatment safety. TRIAL REGISTRATION: PROSPERO
      Registration Number: CRD42013006951.

PMID- 24559431
TI  - Prevalence of acute mountain sickness at 3500 m within and between families: a
      prospective cohort study.
AB  - AIM: To investigate symptoms, prevalence and associated factors of acute mountain
      sickness (AMS) in families upon a fast ascent to 3450 m. METHODS: 87 children, 70
      adolescents, and 155 parents (n=312) were assessed for AMS 8-10 and 20-24 hours
      after fast passive ascent by the Lake Louise Score (LLS). Pain sensitivity and
      oxygen saturation (SO2) were measured and familial clustering was assessed.
      RESULTS: AMS prevalence was significantly lower in children (21%) compared to
      adolescents (34%) and adults (39%) on day 1 (p<0.05), but not on day 2 (18% vs.
      19% and 25%). Cumulative prevalence of AMS was 30, 37, and 45% in children,
      adolescents, and adults, respectively (p<0.001). Familial clustering of AMS was
      consistent and explained 25%-50% of variability in AMS. Pain sensitivity
      significantly increased from low to high altitude and was higher at low altitude
      in those with compared to those without AMS. SO2 at high altitude was not related
      to the presence of AMS. CONCLUSIONS: After fast ascent to 3500 m, AMS prevalence
      was lower in children than in adolescents and adults on day 1, but not on day 2.
      Thus, children may travel at least as safely to an altitude of 3500 m as
      adolescents and adults, even if risk factors (pain sensitivity and heredity) are
      present.

PMID- 24559432
TI  - The transcriptional complex between the BCL2 i-motif and hnRNP LL is a molecular
      switch for control of gene expression that can be modulated by small molecules.
AB  - In a companion paper (DOI: 10.021/ja410934b) we demonstrate that the C-rich
      strand of the cis-regulatory element in the BCL2 promoter element is highly
      dynamic in nature and can form either an i-motif or a flexible hairpin. Under
      physiological conditions these two secondary DNA structures are found in an
      equilibrium mixture, which can be shifted by the addition of small molecules that
      trap out either the i-motif (IMC-48) or the flexible hairpin (IMC-76). In
      cellular experiments we demonstrate that the addition of these molecules has
      opposite effects on BCL2 gene expression and furthermore that these effects are
      antagonistic. In this contribution we have identified a transcriptional factor
      that recognizes and binds to the BCL2 i-motif to activate transcription. The
      molecular basis for the recognition of the i-motif by hnRNP LL is determined, and
      we demonstrate that the protein unfolds the i-motif structure to form a stable
      single-stranded complex. In subsequent experiments we show that IMC-48 and IMC-76
      have opposite, antagonistic effects on the formation of the hnRNP LL-i-motif
      complex as well as on the transcription factor occupancy at the BCL2 promoter.
      For the first time we propose that the i-motif acts as a molecular switch that
      controls gene expression and that small molecules that target the dynamic
      equilibrium of the i-motif and the flexible hairpin can differentially modulate
      gene expression.

PMID- 24559433
TI  - Prevalence of chronic kidney disease and its association with metabolic diseases:
      a cross-sectional survey in Zhejiang province, Eastern China.
AB  - BACKGROUND: The prevalence of chronic kidney disease (CKD) and metabolic diseases
      has increased at different rates in different regions in China. The aim of our
      study was to estimate the prevalence of CKD and to analyze associated risk
      factors of CKD in Zhejiang province, Eastern China. METHODS: A cross-sectional
      survey of 11,013 adults was conducted from September 2009 to June 2012 in
      Zhejiang Province, located in Eastern China. CKD was defined as having an
      estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 or the presence
      of albuminuria. Medical history, physical examination and laboratory data were
      used to diagnose metabolic diseases. Age- and sex-standardized prevalence was
      calculated using the data on the population distribution in China in 2010. We
      examined risk factors associated with decreased renal function and albuminuria
      using multivariate logistic regression. RESULTS: A total of 10,384 adults (94.3%)
      completed the screening. The standardized prevalence of reduced renal function
      (eGFR < 60 mL/min/1.73 m2) was 1.83% (95% CI 1.52-2.13) and that of albuminuria
      was 8.65% (95% CI 7.98-9.31). The overall prevalence of CKD was 9.88% (95% CI
      9.18-10.59). The prevalence of reduced renal function was greater in the eastern
      rural areas in Zhejiang province. Multivariate logistic regression revealed that
      metabolic diseases such as diabetes, obesity, hypertension, and hyperuricemia
      were independent risk factors of CKD. Patients with metabolic diseases had a
      significantly (P < 0.001) higher prevalence of CKD than those without such
      diseases. CONCLUSIONS: CKD has become a severe public health problem in Zhejiang
      Province, and metabolic diseases may increase the risk of CKD in Zhejiang
      population.

PMID- 24559434
TI  - General chemoselective and redox-responsive ligation and release strategy.
AB  - We report a switchable redox click and cleave reaction strategy for conjugating
      and releasing a range of molecules on demand. This chemoselective redox
      responsive ligation (CRRL) and release strategy is based on a redox switchable
      oxime linkage that is controlled by mild chemical or electrochemical redox
      signals and can be performed at physiological conditions without the use of a
      catalyst. Both conjugation and release reactions are kinetically well behaved and
      quantitative. The CRRL strategy is synthetically modular and easily monitored and
      characterized by routine analytical techniques. We demonstrate how the CRRL
      strategy can be used for the dynamic generation of cyclic peptides and the
      ligation of two different peptides that are stable but can be selectively cleaved
      upon changes in the redox environment. We also demonstrate a new redox based
      delivery of cargoes to live cells strategy via the CRRL methodology by
      synthesizing a FRET redox-responsive probe that is selectively activated within a
      cellular environment. We believe the ease of the CRRL strategy should find wide
      use in a range of applications in biology, tissue engineering, nanoscience,
      synthetic chemistry, and material science and will expand the suite of current
      conjugation and release strategies. 

PMID- 24559435
TI  - Smurf1 knocked-down, mesenchymal stem cells and BMP-2 in an electrospun system
      for bone regeneration.
AB  - A sandwich-like system, fabricated with electrospun, poly(lactic-co-glycolic
      acid) (PLGA) membranes incorporating either human recombinant bone morphogenetic
      protein 2 (BMP-2) enriched microspheres, rat bone marrow mesenchymal stem cells
      (rMSC), or rMSC with their Smurf1 (SMAD ubiquitin regulatory factor-1) expression
      knocked down by means of siRNA (rMSC573) at varying densities was evaluated in a
      rat calvarial, critical-size defect. The behavior of four membrane varieties,
      fabricated with different PLGA copolymers, was initially studied in rMSC cultures
      to decide on optimal membrane degradation and cell proliferation and
      differentiation characteristics. PLGA75:25 provided the most stable structure,
      and favored the cell environment. Radiological and histological analyses
      indicated bone repair in animals treated with the PLGA75:25 bioactivated systems.
      We found no synergist interaction between BMP-2 and rMSC 8 to 12 weeks
      postimplantation. By contrast, synergistic defect repair of around 85% was
      detected after 8 weeks of combined BMP-2 and rMSC573 treatment. 

PMID- 24559436
TI  - Evidence for involvement of the monoaminergic system in antidepressant-like
      activity of an ethanol extract of Boerhaavia diffusa and its isolated
      constituent, punarnavine, in mice.
AB  - CONTEXT: Boerhaavia diffusa Linn. (Nyctaginaceae) roots possess potent
      antioxidant, antistress, and anticonvulsant activities. It is used as a medicinal
      plant in Ayurvedic and natural herbal medicines. OBJECTIVE: To evaluate the
      effect of Boerhaavia diffusa root ethanol extract and its active constituent,
      punarnavine, on depression in Swiss albino mice. MATERIALS AND METHODS: Ethanol
      extract (50, 100, and 200 mg/kg, p.o.) and punarnavine (20 and 40 mg/kg, p.o.)
      were separately administered to 22 and 17 groups of mice, respectively, for 14
      successive days followed by testing in the tail suspension and forced swim tests
      (FST). About 2% w/v gum acacia and double distilled water were used as controls
      for the extract and punarnavine, respectively. RESULTS: Antidepressant-like
      effect of the lowest dose (50 mg/kg) of the extract and lower dose (20 mg/kg) of
      punarnavine were found to be comparable to fluoxetine. The ED50 value of the
      ethanol extract was 26.30 mg/kg (FST) and 33.11 mg/kg (tail suspension test); and
      of punarnavine was 15.14 mg/kg (FST) and 17.38 mg/kg (tail suspension test). The
      drugs did not show any significant effect on locomotor activities of mice.
      Prazosin (alpha1-adrenoceptor antagonist), sulpiride (selective D2-receptor
      antagonist), para-chlorophenylalanine) (p-CPA) (tryptophan hydroxylase
      inhibitor), and baclofen (GABAB agonist) significantly attenuated the extract and
      punarnavine induced-antidepressant-like effect in the tail suspension test. The
      extract and punarnavine also significantly reduced mouse brain monoamine oxidase
      (MAO)-A levels, but there was no significant effect on plasma corticosterone
      levels. CONCLUSION: Ethanol extract of Boerhaavia diffusa and punarnavine
      produced an antidepressant-like effect in mice probably through interaction with
      monoaminergic and GABAergic systems.

PMID- 24559437
TI  - Transcriptome sequencing of two parental lines of cabbage (Brassica oleracea L.
      var. capitata L.) and construction of an EST-based genetic map.
AB  - BACKGROUND: Expressed sequence tag (EST)-based markers are preferred because they
      reflect transcribed portions of the genome. We report the development of simple
      sequence repeat (SSR) and single nucleotide polymorphism (SNP) markers derived
      from transcriptome sequences in cabbage, and their utility for map construction.
      RESULTS: Transcriptome sequences were obtained from two cabbage parental lines,
      C1184 and C1234, which are susceptible and resistant to black rot disease,
      respectively, using the 454 platform. A total of 92,255 and 127,522 reads were
      generated and clustered into 34,688 and 40,947 unigenes, respectively. We
      identified 2,405 SSR motifs from the unigenes of the black rot-resistant parent
      C1234. Trinucleotide motifs were the most abundant (66.15%) among the repeat
      motifs. In addition, 1,167 SNPs were detected between the two parental lines. A
      total of 937 EST-based SSR and 97 SNP-based dCAPS markers were designed and used
      for detection of polymorphism between parents. Using an F2 population, we built a
      genetic map comprising 265 loci, and consisting of 98 EST-based SSRs, 21 SNP
      based dCAPS, 55 IBP markers derived from B. rapa genome sequence and 91 public
      SSRs, distributed on nine linkage groups spanning a total of 1,331.88 cM with an
      average distance of 5.03 cM between adjacent loci. The parental lines used in
      this study are elite breeding lines with little genetic diversity; therefore, the
      markers that mapped in our genetic map will have broad spectrum utility.
      CONCLUSIONS: This genetic map provides additional genetic information to the
      existing B. oleracea map. Moreover, the new set of EST-based SSR and dCAPS
      markers developed herein is a valuable resource for genetic studies and will
      facilitate cabbage breeding. Additionally, this study demonstrates the usefulness
      of NGS transcriptomes for the development of genetic maps even with little
      genetic diversity in the mapping population.

PMID- 24559438
TI  - The potential detrimental effect of corticosteroids in prostate cancer.

PMID- 24559439
TI  - Targeting the androgen receptor in metastatic castration-resistant prostate
      cancer.

PMID- 24559440
TI  - New approaches for breast cancer: should Ret kinase be considered as a novel
      therapeutic target?

PMID- 24559441
TI  - Induction chemotherapy in head and neck cancer: are we too ambitious?

PMID- 24559443
TI  - Brooke-Spiegler syndrome tumor spectrum beyond the skin: a patient carrying
      germline R936X CYLD mutation and a somatic CYLD mutation in Brenner tumor.
AB  - Brooke-Spiegler syndrome is a hereditary disorder characterized by a
      predisposition to the development of skin appendage neoplasms and the major and
      minor salivary glands neoplasms. The role of the CYLD mutation in visceral
      neoplasms is still unclear, except for the parathyroid tumor. We report the case
      of a 46-year-old patient with multiple cylindromas and trichoepitheliomas, a
      Brenner tumor of the ovary and a negative family history for Brooke-Spiegler
      phenotype. Genetic analysis revealed R936X germline mutation in the proband, but
      not in the patient's relatives. The same somatic mutation was found in the
      Brenner tumor, together with a novel missense CYLD mutation (D889N), which has
      never been reported in the literature. A founder effect for R936X has been
      hypothesized due to its high prevalence; surprisingly, in our case, this mutation
      seems to be recognized as a de novo mutation. Future studies involving a greater
      number of cases, through the clinical analysis of the familial tumor spectrum and
      the associated molecular pathways, are necessary to understand possible
      genotype/phenotype correlations and the underlying molecular mechanisms. 

PMID- 24559444
TI  - Enzalutamide for the treatment of prostate cancer: results and implications of
      the AFFIRM trial.
AB  - Enzalutamide is a second-generation androgen receptor signaling inhibitor that
      was approved by the US FDA in 2012 for the treatment of metastatic docetaxel
      pretreated castrate-resistant prostate cancer. In preclinical studies,
      enzalutamide demonstrated higher affinity to the androgen receptor compared with
      the first-generation androgen receptor inhibitors. In the well-designed Phase III
      AFFIRM study, enzalutamide treatment showed improved overall survival compared
      with placebo in addition to improvement of all preplanned secondary parameters.
      Overall, enzalutamide seemed to be very well tolerated with a favorable side
      effect profile, with a lower incidence of grade 3-4 adverse events. A potentially
      concerning adverse effect was the occurrence of seizures that were reported in
      approximately 1% of the patients receiving enzalutamide (compared with 0% in the
      placebo arm). This review will summarize the mechanism of action of enzalutamide,
      the preclinical and clinical development that led to its approval focusing on the
      AFFIRM trial results, its safety and efficacy and the ongoing trials, as well as
      patterns of resistance to this drug in the context of five new drugs approved for
      the treatment of metastatic castration-resistant prostate cancer. With a changing
      landscape for these patients, treatment sequencing and best treatment for
      individual patients remains challenging. 

PMID- 24559445
TI  - Free beta-human chorionic gonadotropin, total human chorionic gonadotropin and
      maternal risk of breast cancer.
AB  - BACKGROUND: We investigated whether the free beta-human chorionic gonadotropin
      (free beta-hCG) would provide additional information to that provided by total
      hCG alone and thus be useful in future epidemiological studies relating hCG to
      maternal breast cancer risk. MATERIALS & METHODS: Cases (n = 159) and controls (n
      = 286) were a subset of our previous study within the Northern Sweden Maternity
      Cohort on total hCG during primiparous pregnancy and breast cancer risk. RESULTS:
      The associations between total hCG (hazard ratio: 0.79; 95% CI: 0.49-1.27), free
      beta-hCG (hazard ratio: 0.85; 95% CI: 0.33-2.18) and maternal risk of breast
      cancer were very similar in all analyses and mutual adjustment for either one had
      minor effects on the risk estimates. CONCLUSION: In the absence of a reliable
      assay on intact hCG, total hCG alone can be used in epidemiological studies
      investigating hCG and breast cancer risk, as free beta-hCG does not appear to
      provide any additional information.

PMID- 24559446
TI  - Preclinical studies with JAA-F11 anti-Thomsen-Friedenreich monoclonal antibody
      for human breast cancer.
AB  - AIM: The Thomsen-Friedenreich antigen (TF-Ag) is a disaccharide hidden on normal
      cells, but selectively exposed on the surface of breast, colon, prostate and
      bladder cancer cells. JAA-F11, a highly specific monoclonal antibody to TF-Ag,
      reduces metastasis and prolongs survival in a mouse model. In addition,(124)I-JAA
      F11 localizes 4T1 tumors in mice. These studies continue translation of JAA-F11
      to human breast cancer. MATERIALS & METHODS & RESULTS: Of the 41 human breast
      cancer cell lines tested, 78% were positive for reactivity with JAA-F11 by whole
      cell enzyme immunoassay and positivity occurred unrelated to estrogen,
      progesterone or HER2 receptor status. JAA-F11 inhibited the growth rate of the
      human cancer cell lines tested. At 1 h, approximately 80% of JAA-F11 internalized
      in the three cell lines tested. (124)I-JAA-F11 specifically imaged human triple
      negative tumors in mice by microPET. CONCLUSION: The results highlight the
      potential that humanized JAA-F11 may have for immunotherapy and drug conjugate
      therapy in breast cancer patients.

PMID- 24559448
TI  - Tumor heterogeneity and personalized cancer medicine: are we being outnumbered?
AB  - Tumor heterogeneity is regarded as a major obstacle to successful personalized
      cancer medicine. The lack of reliable response assays reflective of in vivo tumor
      heterogeneity and associated resistance mechanisms hampers identification of
      reliable biomarkers. By contrast, oncogene addiction and paracrine signaling
      enable systemic responses despite tumor heterogeneity. This strengthens
      researchers in their efforts towards personalized cancer medicine. Given the fact
      that tumor heterogeneity is an integral part of cancer evolution, diagnostic
      tools need to be developed in order to better understand the dynamics within a
      tumor. Ultra-deep sequencing may reveal future resistant clones within a (liquid)
      tumor biopsy. On-treatment biopsies may provide insight into intrinsic or
      acquired drug resistance. Subsequently, upfront combinatorial treatment or
      sequential therapy strategies may forestall drug resistance and improve patient
      outcome. Finally, innovative response assays, such as organoid cultures or
      patient-derived tumor xenografts, provide an extra dimension to correlate
      molecular profiles with drug efficacy and control cancer growth. 

PMID- 24559447
TI  - Neural stem cells improve intracranial nanoparticle retention and tumor-selective
      distribution.
AB  - AIM: The purpose of this work is to determine if tumor-tropic neural stem cells
      (NSCs) can improve the tumor-selective distribution and retention of
      nanoparticles (NPs) within invasive brain tumors. MATERIALS & METHODS:
      Streptavidin-conjugated, polystyrene NPs are surface-coupled to biotinylated
      human NSCs. These NPs are large (798 nm), yet when conjugated to tropic cells,
      they are too large to passively diffuse through brain tissue or cross the blood
      tumor barrier. NP distribution and retention was quantified 4 days after
      injections located either adjacent to an intracerebral glioma, in the
      contralateral hemisphere, or intravenously. RESULTS & CONCLUSION: In all three in
      vivo injection paradigms, NSC-coupled NPs exhibited significantly improved tumor
      selective distribution and retention over free-NP suspensions. These results
      provide proof-of-principle that NSCs can facilitate the tumor-selective
      distribution of NPs, a platform useful for improving intracranial drug delivery.

PMID- 24559449
TI  - Sentinel lymph node biopsy in melanoma: controversies and current guidelines.
AB  - Melanoma is a global health problem and the incidence of this disease is rising.
      While localized melanoma has an excellent prognosis, regional and distant disease
      is associated with much poorer outcomes. Optimal treatment for clinically
      localized melanoma requires surgical control of the primary site and accurate
      staging of the regional nodal basin with sentinel lymph node biopsy (SLNB). While
      further data are required to determine if SLNB is associated with a survival
      advantage, currently available data supports the use of SLNB for staging of
      appropriate patients and the procedure may offer benefits beyond staging. This
      article reviews current data that shapes guidelines regarding patient selection
      for SLNB in melanoma and highlights areas where performing this procedure remains
      controversial. 

PMID- 24559450
TI  - mTOR inhibitors: changing landscape of endocrine-resistant breast cancer.
AB  - Most breast cancer (BC) patients have tumors that express hormone receptors
      (HRs). Although endocrine therapy, such as aromatase inhibitors, is very
      effective, most patients with metastatic HR-positive (HR(+)) BC become resistant
      to endocrine therapy at some point in their treatment and subsequently require
      chemotherapy. The PI3K/mTOR pathway is often upregulated in endocrine-resistant
      BC patients and, therefore, has been one of the targets for development of new
      agents. Recently, a Phase III trial (BOLERO-2) in aromatase inhibitor-resistant
      BC patients showed a significant improvement in time to progression with the
      combination of everolimus and exemestane compared with exemestane alone,
      confirming the importance of the PI3K/mTOR pathway in endocrine-resistant BC.
      Side effects from mTOR inhibitors are manageable, but early detection and
      proactive management are required to ensure patients' safety, compliance and
      continuity of treatment. Thus, mTOR inhibitors offer a new hope and promise for
      patients with HR(+) BC. 

PMID- 24559451
TI  - A paradigm shift from anatomic to functional and molecular imaging in the
      detection of recurrent prostate cancer.
AB  - Approximately a third of men with localized prostate cancer who are treated with
      external beam radiation therapy (EBRT) or radical prostatectomy (RP) develop
      biochemical failure (BF). Presumably, BF will progress to distant metastasis and
      prostate cancer-specific mortality in some patients over subsequent years.
      Accurate detection of recurrent disease is important because it allows for
      appropriate treatment selection (e.g., local vs systemic therapy) and early
      delivery of therapy (e.g., salvage EBRT), which affect patient outcome. In this
      article, we discuss the paradigm shift in imaging technology in the detection of
      recurrent prostate cancer. First, we discuss the commonly used morphological and
      anatomical imaging modalities and their role in the post-RP and post-EBRT
      settings of BF. Second, we discuss the accuracy of functional and molecular
      imaging techniques, many of which are under investigation. Further studies are
      needed to establish the role of imaging techniques for detection of cancer
      recurrence and clinical decision-making. 

PMID- 24559452
TI  - Hox gene dysregulation in acute myeloid leukemia.
AB  - In humans, class I homeobox genes (HOX genes) are distributed in four clusters.
      Upstream regulators include transcriptional activators and members of the CDX
      family of transcription factors. HOX genes encode proteins and need cofactor
      interactions, to increase their specificity and selectivity. HOX genes contribute
      to the organization and regulation of hematopoiesis by controlling the balance
      between proliferation and differentiation. Changes in HOX gene expression can be
      associated with chromosomal rearrangements generating fusion genes, such as those
      involving MLL and NUP98, or molecular defects, such as mutations in NPM1 and
      CEBPA for example. Several miRNAs are involved in the control of HOX gene
      expression and their expression correlates with HOX gene dysregulation. HOX genes
      dysregulation is a dominant mechanism of leukemic transformation. A better
      knowledge of their target genes and the mechanisms by which their dysregulated
      expression contributes to leukemogenesis could lead to the development of new
      drugs. 

PMID- 24559453
TI  - Indirect "no-bond" 31P...31P spin-spin couplings in P,P-[3]ferrocenophanes:
      insights from solid-state NMR spectroscopy and DFT calculations.
AB  - No-bond (31)P-(31)P indirect dipolar couplings, which arise from the transmission
      of nuclear spin polarization through interaction of proximal nonbonded electron
      pairs have been investigated in the solid state for a series of closely related
      substituted P,P-[3]ferrocenophanes and model systems. Through variation and
      combination of ligands (phenyl, cyclohexyl, isopropyl) at the two phosphorus
      sites, the P...P distances in these compounds can be varied from 3.49 to 4.06 A.
      Thus, the distance dependence of the indirect no-bond coupling constant J(nb) can
      be studied in a series of closely related compounds. One- and two-dimensional
      solid-state NMR experiments serve to establish the character of these couplings
      and to measure the isotropic coupling constants J(iso), which were found to range
      between 12 and 250 Hz. To develop an understanding of the magnitude of J(nb) in
      terms of molecular structure, their dependences on intramolecular internuclear
      distances and relative orbital orientations is discussed by DFT-calculations on
      suitable models. In agreement with the literature the dependence of J(nb) on the
      P...P distance is found to be exponential; however, the steepness of this curve
      is highly dependent on the internuclear equilibrium distance. For a quantitative
      description, the off-diagonal elements of the expectation value of the Kohn-Sham
      Fock operator in the LMO basis for the LMOs of the two phosphorus lone-pairs is
      proposed. This parameter correlates linearly with the calculated J(nb) values and
      possesses the same distance-dependence. In addition, the simulations indicate a
      distinct dependence of J(nb) on the dihedral angle defined by the two C-P bonds
      providing ligation to the molecular backbone. For disordered materials or those
      featuring multiple sites, conformers, and/or polymorphism, a new double-quantum
      NMR method termed DQ-DRENAR can be used to conveniently measure internuclear
      (31)P-(31)P distances. If conducted on compounds with known P...P distances, such
      measurements can also serve to estimate the magnitude of the anisotropy DeltaJ of
      these no-bond indirect spin-spin couplings. The DFT results suggest that in the
      present series of compounds the magnitude of DeltaJ is strongly correlated with
      that of the isotropic component, as both parameters have analogous distance
      dependences. While our studies indicate a sizable J-anisotropy for the model
      compound 1,8-bis(diphenylphosphino)napthalene (DeltaJ ~ -70 Hz), the
      corresponding values for the P,P-[3]ferrocenophanes are significantly smaller,
      affecting their DQ-DRENAR curves only in a minor way. Based on the above
      insights, the structural aspects of conformational disorder and polymorphism
      observed in some of the P,P-[3]ferrocenophanes are discussed.

PMID- 24559454
TI  - Changes in attachment representations during psychological therapy.
AB  - OBJECTIVES: This review systematically examines research that investigates
      changes in adult attachment representations during psychological therapy. METHOD:
      Studies from two adult attachment approaches are reviewed (interview and self
      report) with the aim of concluding whether psychotherapy can improve attachment
      representations. To guide the interpretation of findings, the methodological
      quality of studies is assessed. RESULTS: The results suggest that attachment
      security increases following therapy, whereas attachment anxiety decreases
      following therapy. Findings are unclear with regard to attachment avoidance.
      Improvements are observed across different methodologies, patient groups,
      therapeutic approaches, and therapy settings. Findings also appear to be
      consistent across different levels of study quality. CONCLUSIONS: Overall,
      research supports the suggestion that attachment styles may alter during the
      course of psychotherapy, but further controlled trials are required to confirm
      this conclusion.

PMID- 24559455
TI  - Effects of experimental conditions on the morphologies, structures and growth
      modes of pulsed laser-deposited CdS nanoneedles.
AB  - CdS nanoneedles with different morphologies, structures, and growth modes have
      been grown on Ni-coated Si(100) surface under different experimental conditions
      by pulsed laser deposition method. The effects of catalyst layer, substrate
      temperature, and laser pulse energy on the growth of the CdS nanoneedles were
      studied in detail. It was confirmed that the formation of the molten catalyst
      spheres is the key to the nucleation of the CdS nanoneedles by observing the
      morphologies of the Ni catalyst thin films annealed at different substrate
      temperatures. Both the substrate temperature and laser pulse energy strongly
      affected the growth modes of the CdS nanoneedles. The secondary growth of the
      smaller nanoneedles on the top of the main nanoneedles was found at appropriate
      conditions. A group of more completed pictures of the growth modes of the CdS
      nanoneedles were presented. 

PMID- 24559456
TI  - Pharmacokinetics of HM-3 after intravitreal administration in mice.
AB  - PURPOSE: HM-3, an RGD-modified endostatin-derived polypeptide, is a potent
      angiogenesis inhibitor synthesized in our laboratory. This study investigated the
      HM-3 pharmacokinetics of intravitreally administered in mice eyes as an anti
      angiogenesis drug for age-related macular degeneration. MATERIALS AND METHODS: A
      total of 288 C57BL/6J mice were evaluated and divided into four groups. Each
      mouse in different groups received single bilateral intravitreal injection with
      HM-3. The concentrations of HM-3 in choroid/sclera, retina and serum were
      determined by indirect competitive enzyme-linked immunosorbent assay. RESULTS:
      After intravitreal administration of doses of 0, 10, 20 and 40 MUg/eye HM-3, the
      observed maximum concentration (Cmax) was 12.98 +/- 1.42, 27.87 +/- 3.64 and
      55.96 +/- 11.94 ng/mg, respectively; and the total area under the curve (AUCtot)
      was 739.23 +/- 190.32, 1171.74 +/- 528.75 and 1777.71 +/- 511.64 h ng/mg; the
      elimination half-life (T1/2) in retina was 104.85 +/- 36.90, 107.42 +/- 35.25 and
      101.12 +/- 15.82 h; the mean residence time (MRT) was 172.46 +/- 63.80, 164.70 +/
      52.72 and 181.32 +/- 26.01 h, respectively. In choroid/sclera, the Cmax was 5.29
      +/- 0.34, 6.29 +/- 1.87 and 8.14 +/- 0.71 ng/mg, respectively; AUCtot was 579.03
      +/- 56.50, 762.20 +/- 201.09 and 720.91 +/-243.87 h ng/mg; T1/2 was 54.04 +/-
      25.99, 59.33 +/- 24.46 and 47.10 +/- 10.00 h, respectively; MRT was 139.98 +/-
      23.93, 155.43 +/- 17.81 and 136.45 +/- 18.17 h, respectively. But in serum, the
      Cmax was 482.00 +/- 38.97, 493.94 +/- 97.64 and 1033.10 +/- 276.33 ng/ml,
      respectively; AUCtot was 21128.55 +/- 4683.68, 53444.57 +/- 16963.99 and 53164.84
      +/-1535.06 h ng/ml; T1/2 was 48.39 +/- 14.89, 47.96 +/- 12.97 and 49.98 +/- 30.07
      h, respectively; MRT was 108.6 +/- 47.17, 159.76 +/- 18.82 and 125.33 +/- 21.41
      h, respectively. CONCLUSIONS: The pharmacokinetic profiles of intravitreal
      administration HM-3 provide the basis for the development of reasonable dosing
      regimens of clinical choroidal neovascularization (CNV) treatment. However, the
      vitreous and blood retinal barrier might be barriers to drug distribution and
      diffusion. In addition, fluid flow for the anterior transport and choroidal blood
      circulation might play important roles for multiple peaking. Carrying out the
      research into pharmacokinetics of HM-3 provides the information for laying down
      drug delivery scheme in mice model of CNV.

PMID- 24559457
TI  - Near-infrared light-triggered drug-delivery vehicle for mitochondria-targeted
      chemo-photothermal therapy.
AB  - A novel drug-delivery vehicle for mitochondria-targeted chemo-photothermal
      therapy was demonstrated. A cytochrome c-specific binding aptamer was employed to
      make the mesoporous silica-encapsulated gold nanorods efficiently accumulate in
      the mitochondria of cancer cells. This nanocarrier can load various hydrophobic
      therapeutic agents acting on mitochondria to enhance the therapeutic efficiency
      and simultaneously depress the toxic side effects. In addition, near-IR treatment
      could induce cytochrome c release and initiation of the mitochondrial pathway of
      apoptosis. Importantly, this multifunctional platform could integrate targeting,
      light-triggered release, and chemo-photothermal therapy into one system. We hope
      that such a system could open the door to the fabrication of a multifunctional
      mitochondria-targeted drug-delivery vehicle for cancer therapy. 

PMID- 24559458
TI  - The reactivity of silylated amino(dichloro)phosphanes in the presence of silver
      salts.
AB  - New cyclic and acylic phosphorus-nitrogen compounds have been synthesized in
      reactions of Hyp-N(SiMe3)PCl2 (hypersilyl = Hyp = (Me3Si)3Si) with silver salts
      of the perfluorinated anions [CF3CO2](-), [CF3SO3](-), and [C6F5](-). Depending
      on the choice of the silver salt, not only AgCl but also Me3SiCl elimination
      could be observed, leading to a transient highly reactive 1,3 dipole molecule.
      This 1,3 dipole molecule was found to be a key species, which can undergo [3 + 2]
      cyclization, when a dipolarophile such as acetonitrile is present. Also,
      dimerization or even cyclo-tetramerization are observed. The occurrence of
      different reaction channels demonstrates that the hypersilyl moiety can act as a
      highly reactive functional group. All new compounds have been characterized by
      single-crystal X-ray diffraction studies. 

PMID- 24559459
TI  - Acute spinal cord injury in rats should target activated autophagy.
AB  - OBJECT: Autophagy is a cellular mechanism of maintaining balance between protein
      synthesis and degradation; the latter can be induced by starvation and
      neurodegenerative disease. Spinal cord injury (SCI) induces necrosis and
      apoptosis. Autophagic flux has not yet been defined, especially the potential
      role of autophagy in relation to apoptosis in different tissue cells. The object
      of this study was to investigate the occurrence of autophagic flux and the
      potential role of autophagy and apoptosis post-SCI in rats. METHODS: Following
      creation of SCI in rats, activation of autophagic flux was detected at the
      protein (LC3, beclin1, and p62) and mRNA (beclin1) levels and on electron
      microscopy images. Distribution of LC3, colocalization of activated caspase-3,
      and changes in expression levels of bcl-2 and Bax were assessed to investigate
      the potential role of autophagy and apoptosis. Sprague-Dawley rats were used, and
      T9-10 hemitransection was performed. Expression levels of LC3, beclin1, p62, bcl
      2, and Bax were assessed by Western blot analysis, and beclin1 mRNA levels were
      assessed by reverse transcription-polymerase chain reaction. Distribution of LC3
      and colocalization of activated caspase-3 were analyzed by immunohistochemistry.
      Autophagosome formation was investigated by electron microscopy. RESULTS: The
      authors found a dramatic elevation in LC3 and beclin1 levels near the scar
      region. Using double staining, they observed that upregulation of LC3 started at
      4 hours in neurons and at 3 days in astrocytes after SCI. Confocal images
      indicated that the percentage of neurons with apoptosis was reduced, while the
      percentage of astrocytes with apoptosis was high at 4 hours, 8 hours, and 1 day
      post-SCI but decreased sharply at 3 days. Electron microscopy images provided
      evidence of autophagosome formation. Elimination of p62 indicated occurrence of
      autophagic flux. Expression levels of bcl-2 and Bax were increased and decreased,
      respectively, near the injury site. CONCLUSIONS: The results of this research
      demonstrated that autophagic flux is activated after SCI. Potentially, inhibition
      of apoptosis could be a target to promote neural recovery.

PMID- 24559460
TI  - High-grade spondylolisthesis treated using a modified Bohlman technique: results
      among multiple surgeons.
AB  - OBJECT: The ideal surgical management of high-grade spondylolisthesis remains
      unclear. Concerns regarding the original Bohlman transsacral interbody fusion
      technique with stand-alone autologous fibular strut include late graft fracture
      and incomplete reduction of lumbosacral kyphosis. The authors' goal was to
      evaluate the radiographic and surgical outcomes of patients treated for high
      grade spondylolisthesis with either transsacral S-1 screws or standard pedicle
      screw fixation augmenting the Bohlman posterior transsacral interbody fusion
      technique. METHODS: A retrospective review of patients who underwent fusion for
      high-grade spondylolisthesis in which a Bohlman oblique posterior interbody
      fusion augmented with either transsacral or standard pedicle screw fixation was
      performed by 4 spine surgeons was completed. Estimated blood loss, operating
      time, perioperative complications, and need for revision surgery were evaluated.
      Upright pre- and postsurgical lumbar spine radiographs were compared for slip
      percent and slip angle. RESULTS: Sixteen patients (12 female and 4 male) with an
      average age of 29 years (range 9-66 years) were evaluated. The average clinical
      follow-up was 78 months (range 5-137 months) and the average radiographic follow
      up was 48 months (range 5-108 months). Ten L4-S1 and 6 L5-S1 fusions were
      performed. Five fibular struts and 11 titanium mesh cages were used for interbody
      fusion. Six patients had isolated transsacral screws placed, with 2 (33%) of the
      6 requiring revision surgery for nonunion. No nonunions were observed in patients
      undergoing spanning pedicle screw fixation augmenting the interbody graft. Six
      patients experienced perioperative complications including 3 iliac crest site
      infections, 1 L-5 radiculopathy without motor involvement, 1 deep vein
      thrombosis, and 1 epidural hematoma requiring irrigation and debridement. The
      average estimated blood loss and operating times were 763 ml and 360 minutes,
      respectively. Slip percent improved from an average of 62% to 37% (n = 16; p <
      0.01) and slip angle improved from an average of 18 degrees  to 8 degrees  (n =
      16; p < 0.01). No patient experienced L-5 or other motor deficit postoperatively.
      CONCLUSIONS: The modified Bohlman technique for treatment of high-grade
      spondylolisthesis has reproducible outcomes among multiple surgeons and results
      in significant improvements in slip percent and slip angle. Fusion rates were
      high (14 of 16; 88%), especially with spanning instrumentation augmenting the
      oblique interbody fusion. Rates of L-5 motor deficit were low in comparison with
      techniques involving reduction of the anterolisthesis.

PMID- 24559461
TI  - Is in vivo manual palpation for thoracic pedicle screw instrumentation reliable?
AB  - OBJECT: Previous reports on the accuracy of manual palpation for thoracic pedicle
      screw placement have been restricted to cadaveric studies. Authors of the present
      novel study assessed the accuracy of manual palpation for the detection of medial
      and lateral pedicle breaches during thoracic spine surgery in living adult
      humans. METHODS: Pedicle tracks were created freehand and manually palpated using
      a ball-tipped probe. Postoperative CT scans of all implanted thoracic and L-1
      screws were evaluated with respect to screw position and the pedicle wall.
      RESULTS: Five hundred twenty-five pedicle track/screw placements were compared.
      There were 21 pedicles with medial breaches measuring >= 2 mm. The surgeon
      correctly identified only 4 of these pedicle tracks as having a medial breach.
      The surgeon correctly identified 17 of 128 pedicles with a significant (>= 2 mm)
      lateral breach. One hundred two screw placements had no measurable breach in any
      direction (medial, lateral, or foraminal). The surgeon correctly identified 98%
      of these ideally placed screws. CONCLUSIONS: In this real-time study of thoracic
      pedicle screw placement, the accuracy of manual palpation for detecting medial or
      lateral breaches that were >= 2 mm was disturbingly low. These findings are
      consistent with those in recent cadaveric evaluations of palpation accuracy and
      point to the critical need for more reliable alternative methods to assess
      pedicle integrity during the placement of thoracic pedicle screws for spine
      instrumentation surgery.

PMID- 24559462
TI  - Health state utility of patients with single-level cervical degenerative disc
      disease: comparison of anterior cervical discectomy and fusion with cervical disc
      arthroplasty.
AB  - OBJECT: Cost-effectiveness analysis (CEA) of medical interventions has become
      increasingly relevant to the discussion of optimization of care. The use of
      utility scales in CEA permits a quantitative assessment of effectiveness of a
      given intervention. There are no published utility values for degenerative disc
      disease (DDD) of the cervical spine, anterior cervical discectomy and fusion
      (ACDF), or cervical disc replacement (CDR). The purpose of this study was to
      define health utility values for those health states. METHODS: The 36-Item Short
      Form Health Survey data from the ProDisc-C investigational device exemption study
      were obtained for single-level DDD at baseline and 24 months postoperatively
      after ACDF or CDR procedures. Patients in the original study were randomized to
      either ACDF or CDR. Utilizing a commercially available Short Form-6 dimensions
      program, utility scores were calculated for each health state using a set of
      parametric preference weights obtained from a sample of the general population
      using the recognized valuation technique of standard gamble. RESULTS: The
      baseline health state utility (HSU) value for a patient with single-level DDD was
      0.54 in both the ACDF and CDR groups. Postoperative changes in HSU values were
      seen in both intervention groups at 24 months. Cervical disc replacement had a
      HSU value of 0.72. Anterior cervical discectomy and fusion was found to have a
      postoperative utility state of 0.71. No statistically significant difference was
      found in the HSU for ACDF and CDR at 24 months of follow-up. CONCLUSIONS: This
      study represents the first calculated HSU value for a patient with single-level
      cervical DDD. Additionally, 2 common treatment interventions for this disease
      state were assessed. Both treatments were found to have significant impact on the
      HSU values. These values are integral to future CEA of ACDF and CDR.

PMID- 24559463
TI  - Kinetic analysis of anterior cervical discectomy and fusion supplemented with
      transarticular facet screws.
AB  - OBJECT The clinical success rates of anterior cervical discectomy and fusion
      (ACDF) procedures are substantially reduced as more cervical levels are included
      in the fusion procedure. One method that has been proposed as an adjunctive
      technique for multilevel ACDF is the placement of screws across the facet joints
      ("transfacet screws"). However, the biomechanical stability imparted by
      transfacet screw placement (either unilaterally or bilaterally) has not been
      reported. Therefore, the purpose of this study was to determine the acute
      stability conferred by implementation of unilateral and bilateral transfacet
      screws to an ACDF construct. METHODS Eight C2-T1 fresh-frozen human cadaveric
      spines (3 female and 5 male; mean age 50 years) were tested. Three different
      instrumentation variants were performed on cadaveric cervical spines across C4-7:
      1) ACDF with an intervertebral spacer and standard plate/screw instrumentation;
      2) ACDF with an intervertebral spacer and standard plate/screw instrumentation
      with unilateral facet screw placement; and 3) ACDF with an intervertebral spacer
      and standard plate/screw instrumentation with bilateral facet screw placement.
      Kinetic ranges of motion in flexion-extension, lateral bending, and axial
      rotation at 1.5 Nm were captured after each of these procedures and were
      statistically analyzed for significance. RESULTS All 3 fixation scenarios
      produced statistically significant reductions (p < 0.05) in all 3 bending planes
      compared with the intact condition. The addition of a unilateral facet screw to
      the ACDF construct produced significant reductions at the C4-5 and C6-7 levels in
      lateral bending and axial rotation but not in flexion-extension motion. Bilateral
      facet screw fixation did not produce any statistically significant decreases in
      flexion-extension motion compared with unilateral facet screw fixation. However,
      in lateral bending, significant reductions at the C4-5 and C5-6 levels were
      observed with the addition of a second facet screw. The untreated, adjacent
      levels (C2-3, C3-4, and C7-1) did not demonstrate significant differences in
      range of motion. CONCLUSIONS The data demonstrated that adjunctive unilateral
      facet screw fixation to an ACDF construct provides significant gains in stability
      and should be considered a potential option for increasing the likelihood for
      obtaining a successful arthrodesis for multilevel ACDF procedures.

PMID- 24559464
TI  - Spaser made of graphene and carbon nanotubes.
AB  - Spaser is a nanoscale source of surface plasmons comprising a plasmonic resonator
      and gain medium to replenish energy losses. Here we propose a carbon-based spaser
      design in which a graphene nanoflake (GNF) resonator is coupled to a carbon
      nanotube (CNT) gain element. We theoretically demonstrate that the optically
      excited CNT can nonradiatively transfer its energy to the localized plasmon modes
      of the GNF because of the near-field interaction between the modes and the CNT
      excitons. By calculating the localized fields of the plasmon modes and the matrix
      elements of the plasmon-exciton interaction, we find the optimal geometric and
      material parameters of the spaser that yield the highest plasmon generation rate.
      The results obtained may prove useful in designing robust and ultracompact
      coherent sources of surface plasmons for plasmonic nanocircuits. 

PMID- 24559465
TI  - Validation of cell-cycle arrest biomarkers for acute kidney injury using clinical
      adjudication.
AB  - RATIONALE: We recently reported two novel biomarkers for acute kidney injury
      (AKI), tissue inhibitor of metalloproteinases (TIMP)-2 and insulin-like growth
      factor binding protein 7 (IGFBP7), both related to G1 cell cycle arrest.
      OBJECTIVES: We now validate a clinical test for urinary [TIMP-2].[IGFBP7] at a
      high-sensitivity cutoff greater than 0.3 for AKI risk stratification in a diverse
      population of critically ill patients. METHODS: We conducted a prospective
      multicenter study of 420 critically ill patients. The primary analysis was the
      ability of urinary [TIMP-2].[IGFBP7] to predict moderate to severe AKI within 12
      hours. AKI was adjudicated by a committee of three independent expert
      nephrologists who were masked to the results of the test. MEASUREMENTS AND MAIN
      RESULTS: Urinary TIMP-2 and IGFBP7 were measured using a clinical immunoassay
      platform. The primary endpoint was reached in 17% of patients. For a single
      urinary [TIMP-2].[IGFBP7] test, sensitivity at the prespecified high-sensitivity
      cutoff of 0.3 (ng/ml)(2)/1,000 was 92% (95% confidence interval [CI], 85-98%)
      with a negative likelihood ratio of 0.18 (95% CI, 0.06-0.33). Critically ill
      patients with urinary [TIMP-2].[IGFBP7] greater than 0.3 had seven times the risk
      for AKI (95% CI, 4-22) compared with critically ill patients with a test result
      below 0.3. In a multivariate model including clinical information, urinary [TIMP
      2].[IGFBP7] remained statistically significant and a strong predictor of AKI
      (area under the curve, 0.70, 95% CI, 0.63-0.76 for clinical variables alone, vs.
      area under the curve, 0.86, 95% CI, 0.80-0.90 for clinical variables plus [TIMP
      2].[IGFBP7]). CONCLUSIONS: Urinary [TIMP-2].[IGFBP7] greater than 0.3
      (ng/ml)(2)/1,000 identifies patients at risk for imminent AKI. Clinical trial
      registered with www.clinicaltrials.gov (NCT 01573962).

PMID- 24559466
TI  - Computational study of the stability of the miniprotein trp-cage, the GB1 beta
      hairpin, and the AK16 peptide, under negative pressure.
AB  - Although hot, cold, and high pressure denaturation are well characterized, the
      possibility of negative pressure unfolding has received much less attention.
      Proteins under negative pressure, however, are important in applications such as
      medical ultrasound, and the survival of biopoloymers in the xylem and adjacent
      parenchyma cells of vascular plants. In addition, negative pressure unfolding is
      fundamentally important in obtaining a complete understanding of protein
      stability and naturally complements previous studies of high pressure
      denaturation. We use extensive replica-exchange molecular dynamics (REMD)
      simulations and thermodynamic analysis to obtain folding/unfolding equilibrium
      phase diagrams for the miniprotein trp-cage (alpha-structure, 20-residue), the
      GB1 beta-hairpin (beta-structure, 16-residue), and the AK16 peptide (alpha-helix,
      16-residue). Although the trp-cage is destabilized by negative pressure, the GB1
      beta-hairpin and AK16 peptide are stabilized by this condition. 

PMID- 24559467
TI  - Cytogenetic and molecular analyses of de novo translocation dic(9;13)(p11.2;p12)
      in an infertile male.
AB  - BACKGROUND: Whole arm t(9;13)(p11;p12) translocations are rare and have been
      described only a few times; all of the previously reported cases were familial.
      RESULTS: We present here an infertile male carrier with a whole-arm reciprocal
      translocation dic(9;13)(p11.2;p12) revealed by GTG-, C-, and NOR-banding
      karyotypes with no mature sperm cells in his ejaculate. FISH and genome-wide 400
      K CGH microarray (Agilent) analyses demonstrated a balanced chromosome complement
      and further characterised the abnormality as a dicentric chromosome (9;13):
      dic(9;13)(pter->p11.2::p12->qter),neo(9)(pter->p12->neo->p11.2). An analysis of
      the patient's ejaculated cells identified immature germ cells at different phases
      of spermatogenesis but no mature spermatozoa. Most (82.5%) of the germ cells were
      recognised as spermatocytes at stage I, and the cell nuclei were most frequently
      found in pachytene I (41.8%). We have also undertaken FISH analysis and
      documented an increased rate of aneuploidy of chromosomes 15, 18, X and Y in the
      peripheral blood leukocytes of our patient. To study the aneuploidy risk in
      leukocytes, we have additionally included 9 patients with non-obstructive
      azoospermia with normal karyotypes. CONCLUSIONS: We propose that the azoospermia
      observed in the patient with the dic(9;13)(p11.2;p12) translocation was most
      likely a consequence of a very high proportion (90%) of association between XY
      bivalents and quadrivalent formations in prophase I.

PMID- 24559468
TI  - Mount Everest and Makalu cold injury amputation: 40 years on.
AB  - Freezing cold injuries (frostbite) of the extremities are a common injury among
      alpinists participating in high altitude expeditions, particularly during
      inclement weather conditions. Anecdotally, a digit that has suffered frostbite
      may be at greater risk to future cold injuries. In this case study, we profile a
      62-year-old elite alpinist who suffered multiple digit amputations on both his
      hands and foot after historic summit attempts on Makalu (8481 m) and Mt. Everest
      (8848 m) in 1974-1979. We describe the clinical treatment he received at that
      time, and follow up his case 40 years after the first incidence of frostbite
      utilizing a noninvasive evaluation of hand and foot function to a cold stress
      test, including rates of re-warming to both injured and non-injured digits.
      Finger rates of recovery to the cold stress test were not different (0.8 vs. 1.0
      degrees C.min(-1)) except one (injured, left middle finger, distal phalanx; 0.4
      degrees C.min(-1)). Toe recovery rates after cold-water immersion were identical
      between previously injured and non-injured toes (0.2 degrees C.min(-1)).
      Thermocouple data indicate that this alpinist's previous frostbite injuries may
      not have significantly altered his digit rates of re-warming during passive
      recovery compared to his non-injured digits.

PMID- 24559470
TI  - Undercorrection of hypernatremia is frequent and associated with mortality.
AB  - BACKGROUND: About 1% of patients admitted to the Emergency Department (ED) have
      hypernatremia, a condition associated with a mortality rate of 20 to 60%.
      Management recommendations originate from intensive care unit studies, in which
      patients and medical diseases differ from those in ED. METHODS: We
      retrospectively studied clinical characteristics, treatments, and outcomes of
      severely hypernatremic patients in the ED and risk factors associated with death
      occurrence during hospitalization. RESULTS: During 2010, 85 cases of severe
      hypernatremia >= 150 mmol/l were admitted to ED. Hypernatremia occurred in frail
      patients: mean age 79.7 years, 55% institutionalized, 28% with dementia.Twenty
      four percent of patients died during hospitalization. Male gender and low mean
      blood pressure (MBP) were independently associated with death, as well as slow
      natremia correction speed, but not the severity of hyperosmolarity at admission.
      Infusion solute was inappropriate for 45% of patients with MBP <70 mmHg who
      received hypotonic solutes and 22% of patients with MBP >= 70 mmHg who received
      isotonic solutes or were not perfused. CONCLUSIONS: This is the first study
      assessing outcome of hypernatremic patients in the ED according to the treatment
      provided. It appears that not only a too quick, but also a too slow correction
      speed is associated with an increased risk of death regardless of initial
      natremia. Medical management of hypernatremic patients must be improved regarding
      evaluation and treatment.

PMID- 24559471
TI  - Hydroxylated HMPA enhances both reduction potential and proton donation in SmI2
      reactions.
AB  - HMPA is known to increase the reduction potential of SmI2. However, in many
      cases, the transferred electron returns from the radical anion of the substrate
      back to the Sm(3+). This could be avoided by an efficient trapping of the radical
      anion: e.g., by protonation. However, bimolecular protonation by a proton donor
      from the bulk may be too slow to compete with the back electron transfer process.
      An efficient unimolecular protonation could be achieved by using a proton donor
      which complexes to SmI2, in which case the proton is unimolecularly transferred
      within the ion pair. A derivative of HMPA in which one of the methyl groups was
      substituted by a CH2CH2OH unit was synthesized. Cyclic voltammetry studies have
      shown that it resembles HMPA in its ability to enhance the reduction potential of
      SmI2, and reactivity studies show that it has also efficient proton shift
      capabilities. The various aspects of this additive were examined in the reactions
      of SmI2 with three substrates: benzyl chloride, methyl cinnamate, and anthracene.

PMID- 24559472
TI  - The effects of exercise on cognition in Parkinson's disease: a systematic review.
AB  - Cognitive impairments are highly prevalent in Parkinson's disease (PD) and can
      substantially affect a patient's quality of life. These impairments remain
      difficult to manage with current clinical therapies, but exercise has been
      identified as a possible treatment. The objective of this systematic review was
      to accumulate and analyze evidence for the effects of exercise on cognition in
      both animal models of PD and human disease. This systematic review was conducted
      according to the Preferred Reporting Items for Systematic reviews and Meta
      Analyses (PRISMA) statement. Fourteen original reports were identified, including
      six pre-clinical animal studies and eight human clinical studies. These studies
      used various exercise interventions and evaluated many different outcome
      measures; therefore, only a qualitative synthesis was performed. The evidence
      from animal studies supports the role of exercise to improve cognition in humans
      through the promotion of neuronal proliferation, neuroprotection and
      neurogenesis. These findings warrant more research to determine what roles these
      neural mechanisms play in clinical populations. The reports on cognitive changes
      in clinical studies demonstrate that a range of exercise programs can improve
      cognition in humans. While each clinical study demonstrated improvements in a
      marker of cognition, there were limitations in each study, including non
      randomized designs and risk of bias. The Grading of Recommendations Assessment,
      Development and Evaluation (GRADE) system was used and the quality of the
      evidence for human studies were rated from "low" to "moderate" and the strength
      of the recommendations were rated from "weak" to "strong". Studies that assessed
      executive function, compared to general cognitive abilities, received a higher
      GRADE rating. Overall, this systematic review found that in animal models
      exercise results in behavioral and corresponding neurobiological changes in the
      basal ganglia related to cognition. The clinical studies showed that various
      types of exercise, including aerobic, resistance and dance can improve cognitive
      function, although the optimal type, amount, mechanisms, and duration of exercise
      are unclear. With growing support for exercise to improve not only motor
      symptoms, but also cognitive impairments in PD, health care providers and policy
      makers should recommend exercise as part of routine management and
      neurorehabilitation for this disorder. 

PMID- 24559473
TI  - Strand-specific RNA-Seq reveals widespread and developmentally regulated
      transcription of natural antisense transcripts in Plasmodium falciparum.
AB  - BACKGROUND: Advances in high-throughput sequencing have led to the discovery of
      widespread transcription of natural antisense transcripts (NATs) in a large
      number of organisms, where these transcripts have been shown to play important
      roles in the regulation of gene expression. Likewise, the existence of NATs has
      been observed in Plasmodium but our understanding towards their genome-wide
      distribution remains incomplete due to the limited depth and uncertainties in the
      level of strand specificity of previous datasets. RESULTS: To gain insights into
      the genome-wide distribution of NATs in P. falciparum, we performed RNA-ligation
      based strand-specific RNA sequencing at unprecedented depth. Our data indicate
      that 78.3% of the genome is transcribed during blood-stage development. Moreover,
      our analysis reveals significant levels of antisense transcription from at least
      24% of protein-coding genes and that while expression levels of NATs change
      during the intraerythrocytic developmental cycle (IDC), they do not correlate
      with the corresponding mRNA levels. Interestingly, antisense transcription is not
      evenly distributed across coding regions (CDSs) but strongly clustered towards
      the 3'-end of CDSs. Furthermore, for a significant subset of NATs, transcript
      levels correlate with mRNA levels of neighboring genes.Finally, we were able to
      identify the polyadenylation sites (PASs) for a subset of NATs, demonstrating
      that at least some NATs are polyadenylated. We also mapped the PASs of 3443
      coding genes, yielding an average 3' untranslated region length of 523 bp.
      CONCLUSIONS: Our strand-specific analysis of the P. falciparum transcriptome
      expands and strengthens the existing body of evidence that antisense
      transcription is a substantial phenomenon in P. falciparum. For a subset of
      neighboring genes we find that sense and antisense transcript levels are
      intricately linked while other NATs appear to be regulated independently of mRNA
      transcription. Our deep strand-specific dataset will provide a valuable resource
      for the precise determination of expression levels as it separates sense from
      antisense transcript levels, which we find to often significantly differ. In
      addition, the extensive novel data on 3' UTR length will allow others to perform
      searches for regulatory motifs in the UTRs and help understand post-translational
      regulation in P. falciparum.

PMID- 24559475
TI  - OGlcNAcylation and phosphorylation have opposing structural effects in tau:
      phosphothreonine induces particular conformational order.
AB  - Phosphorylation and OGlcNAcylation are dynamic intracellular protein post
      translational modifications that frequently are alternatively observed on the
      same serine and threonine residues. Phosphorylation and OGlcNAcylation commonly
      occur in natively disordered regions of proteins, and often have opposing
      functional effects. In the microtubule-associated protein tau,
      hyperphosphorylation is associated with protein misfolding and aggregation as the
      neurofibrillary tangles of Alzheimer's disease, whereas OGlcNAcylation stabilizes
      the soluble form of tau. A series of peptides derived from the proline-rich
      domain (residues 174-251) of tau was synthesized, with free Ser/Thr hydroxyls,
      phosphorylated Ser/Thr (pSer/pThr), OGlcNAcylated Ser/Thr, and
      diethylphosphorylated Ser/Thr. Phosphorylation and OGlcNAcylation were found by
      CD and NMR to have opposing structural effects on polyproline helix (PPII)
      formation, with phosphorylation favoring PPII, OGlcNAcylation opposing PPII, and
      the free hydroxyls intermediate in structure, and with phosphorylation structural
      effects greater than OGlcNAcylation. For tau196-209, phosphorylation and
      OGlcNAcylation had similar structural effects, opposing a nascent alpha-helix.
      Phosphomimic Glu exhibited PPII-favoring structural effects. Structural changes
      due to Thr phosphorylation were greater than those of Ser phosphorylation or Glu,
      with particular conformational restriction as the dianion, with mean (3)JalphaN =
      3.5 Hz (pThr) versus 5.4 Hz (pSer), compared to 7.2, 6.8, and 6.2 Hz for Thr,
      Ser, and Glu, respectively, values that correlate with the backbone torsion angle
      phi. Dianionic phosphothreonine induced strong phosphothreonine amide protection
      and downfield amide chemical shifts (deltamean = 9.63 ppm), consistent with
      formation of a stable phosphate-amide hydrogen bond. These data suggest
      potentially greater structural importance of threonine phosphorylation than
      serine phosphorylation due to larger induced structural effects. 

PMID- 24559476
TI  - Hesperidin, a flavanoglycone attenuates experimental diabetic neuropathy via
      modulation of cellular and biochemical marker to improve nerve functions.
AB  - AIM: Diabetic neuropathy (DN) is one of the most common long-term complications
      of diabetes mellitus and clinically can be characterized by an elevated
      nociceptive response with electrophysiological conduction abnormalities. The
      present investigation was designed to evaluate the neuroprotective effect of
      hesperidin against STZ induced diabetic neuropathic pain in laboratory rats.
      MATERIALS AND METHODS: DN was induced in Sprague-Dawley rats (150-200 g) by
      intraperitoneal administration of streptozotocin (STZ) (55 mg/kg, p.o.). Rats
      were divided into various groups, namely, STZ control (vehicle), hesperidin (25,
      50, and 100 mg/kg, p.o.), insulin (10 IU/kg, s.c.), and combination of hesperidin
      (100 mg/kg, p.o.) with insulin (10 IU/kg, s.c.) for 4 weeks. Various behavioral
      (allodynia and hyperalgesia), biochemical parameters [oxido-nitosative stress, Na
      K-ATPase, aldose reductase (AR)], and molecular changes (TNF-alpha and IL-1beta)
      along with hemodynamic changes were determined. RESULTS: Rats treated with
      hesperidin (50 and 100 mg/kg, p.o., 4 weeks) significantly reduced (p < 0.05)
      hyperglycemia and its metabolic abnormalities induced by intraperitoneal
      administration of STZ. The decreased nociceptive threshold, motor nerve
      conduction velocity (MNCV) and sensory nerve conduction velocity (SNCV), serum
      insulin as well as Na-K-ATPase activity were significantly increase (p < 0.05) by
      hesperidin (50 and 100 mg/kg, p.o.) treatment. It significantly attenuated (p <
      0.05) elevated glycated hemoglobin, AR activity, oxido-nitrosative stress, neural
      calcium, and pro-inflammatory cytokines (TNF-alpha and IL-1beta) levels.
      Histological aberration induced after STZ administration was restored by
      administration of hesperidin (50 and 100 mg/kg, p.o.) CONCLUSION: In combination
      with insulin, hesperidin not only attenuated the diabetic condition but also
      reversed neuropathic pain via control over hyperglycemia as well as
      hyperlipidemia to down-regulate generation of free radical, release of pro
      inflammatory cytokines as well as elevation in membrane bound enzyme.

PMID- 24559478
TI  - Prospects for lentiviral vector mediated prostaglandin F synthase gene delivery
      in monkey eyes in vivo.
AB  - Currently, the most effective outflow drugs approved for clinical use are
      prostaglandin F2alpha analogues, but these require daily topical self-dosing and
      have various intraocular, ocular surface and extraocular side effects. Lentiviral
      vector-mediated delivery of the prostaglandin F synthase (PGFS) gene, resulting
      in long-term reduction of intraocular pressure (IOP), may eliminate off-target
      tissue effects and the need for daily topical PGF2alpha self-administration.
      Lentiviral vector-mediated delivery of the PGFS gene to the anterior segment has
      been achieved in cats and non-human primates. Although these results are
      encouraging, our studies have identified a number of challenges that need to be
      overcome for prostaglandin gene therapy to be translated into the clinic. Using
      examples from our work in non-human primates, where we were able to achieve a
      significant reduction in IOP (2 mm Hg) for 5 months after delivery of the cDNA
      for bovine PGF synthase, we identify and discuss these issues and consider
      several possible solutions.

PMID- 24559477
TI  - Early life programming as a target for prevention of child and adolescent mental
      disorders.
AB  - This paper concerns future policy development and programs of research for the
      prevention of mental disorders based on research emerging from fetal and early
      life programming. The current review offers an overview of findings on pregnancy
      exposures such as maternal mental health, lifestyle factors, and potential
      teratogenic and neurotoxic exposures on child outcomes. Outcomes of interest are
      common child and adolescent mental disorders including hyperactive, behavioral
      and emotional disorders. This literature suggests that the preconception and
      perinatal periods offer important opportunities for the prevention of deleterious
      fetal exposures. As such, the perinatal period is a critical period where future
      mental health prevention efforts should be focused and prevention models
      developed. Interventions grounded in evidence-based recommendations for the
      perinatal period could take the form of public health, universal and more
      targeted interventions. If successful, such interventions are likely to have
      lifelong effects on (mental) health. 

PMID- 24559479
TI  - pH-dependent coordination of Pb2+ to metallothionein2: structures and insight
      into lead detoxification.
AB  - Lead is a toxic heavy metal whose detoxification in organisms is mainly carried
      out by its coordination with some metalloproteins such as metallothioneins (MTs).
      Two Pb-MT complexes, named as Pb7-MT2(I) and Pb7-MT2(II), form under neutral and
      weakly acidic conditions, respectively. However, the structures of the two
      complexes, which are crucial for a better understanding of the detoxification
      mechanism of Pb-MTs, have not been clearly elucidated. In this Work, coordination
      of Pb(2+) with rabbit liver apo-MT2, as well as with the two individual domains
      (apo-alphaMT2 and apo-betaMT2) at different pH, were studied by combined
      spectroscopic (UV-visible, circular dichroism, and NMR) and computational
      methods. The results showed that in Pb7-MT2(I) the Pb(2+) coordination is in the
      trigonal pyramidal Pb-S3 mode, whereas the Pb7-MT2(II) complex contains mixed
      trigonal pyramidal Pb-S3, distorted trigonal pyramidal Pb-S2O1, and distorted
      quadrilateral pyramidal Pb-S3O1 modes. The O-donor ligand in Pb7-MT2(II) was
      identified as the carboxyl groups of the aspartic acid residues at positions 2
      and 56. Our studies also revealed that Pb7-MT2(II) has a greater acid tolerance
      and coordination stability than Pb7-MT2(I), thereby retaining the Pb(2+)
      coordination at acidic pH. The higher flexibility of Pb7-MT2(II) renders it more
      accessible to lysosomal proteolysis than Pb7-MT2(I). Similar spectral features
      were observed in the coordination of Pb(2+) by human apo-MT2, suggesting a
      commonality among mammalian MT2s in the Pb(2+) coordination chemistry. 

PMID- 24559480
TI  - Mometasone furoate-loaded cold processed oil-in-water emulsions: in vitro and in
      vivo studies.
AB  - Over the years, research has focused on strategies to increase benefit/risk ratio
      of corticoids. However, vehicles intended for topical glucocorticoids delivery
      with an improved benefit/risk ratio are still on demand. The aim of this work was
      the in vitro and in vivo characterization of cold processed oil-in-water (o/w)
      emulsions intended for mometasone furoate (MF) delivery to induce drug targeting
      to upper skin strata, decreasing adverse effects. Two o/w emulsions, containing
      0.1% of MF, were developed differing in the glycol used (2-methyl-2,4-pentanediol
      - PT and ethoxydiglycol - TC emulsions). In vitro permeation studies revealed
      that these emulsions are suitable vehicles for the delivery of MF containing
      ingredients which are responsible for a drastically increased on the permeability
      coefficients of MF from a theoretical value of 1.18 * 10(-4 )cm/h to 5.20 * 10(
      4) +/- 2.05 * 10(-4 )cm/h and 6.30 * 10(-4) +/- 2.94 * 10(-4 )cm/h, for PT and
      TC, respectively. The tape stripping results showed that the amount of drug that
      reached the viable skin layers was very low (1.99 %) and the amount that remained
      in the stratum corneum (SC) was 10.61%. The in vivo studies showed that the
      developed formulations decreased the edema and erythema in mice skin in more that
      90%, assuring, at least, the same anti-inflammatory effect compared with the
      commercial cream. PT placebo demonstrated to contribute to restore the skin
      barrier by increasing the amount of lipids within the human skin.

PMID- 24559481
TI  - Sensitivity and selectivity of switchable reagent ion soft chemical ionization
      mass spectrometry for the detection of picric acid.
AB  - We have investigated the reactions of NO(+), H3O(+), O2(+), and Kr(+) with picric
      acid (2,4,6 trinitrophenol, C6H3N3O7, PiA) using a time-of-flight mass
      spectrometer with a switchable reagent ion source. NO(+) forms a simple adduct
      ion PiA.NO(+), while H3O(+) reacts with PiA via nondissociative proton transfer
      to form PiAH(+). In contrast, both O2(+) and Kr(+) react with PiA by
      nondissociative charge transfer to produce PiA(+). For Kr(+), we also observe
      dissociation of PiA, producing NO2(+) with a branching percentage of
      approximately 40%. For the reagent ions H3O(+) and O2(+) (and operating the drift
      tube with normal laboratory air), we find that the intensities of the PiAH(+) and
      PiA(+) ions both exhibit a peak at a given drift-tube voltage (which is humidity
      dependent). This unusual behavior implies a peak in the detection sensitivity of
      PiA as a function of the drift-tube voltage (and hence E/N). Aided by electronic
      structure calculations and our previous studies of trinitrotoluene and
      trinitrobenzene, we provide a possible explanation for the observed peak in the
      detection sensitivity of PiA. 

PMID- 24559483
TI  - Detecting the developmental toxicity of bFGF in the embryonic stem cell test
      using differential gene expression of differentiation-related genes.
AB  - Basic fibroblast growth factor (bFGF) is a mitogenic cytokine that can stimulate
      mesoderm-and neuroectoderm-originated cell proliferation. This study was
      performed to investigate the effects of bFGF on cell differentiation and the
      expression of specific markers at different embryonic developmental stages. We
      firstly evaluated the embryotoxic potential of bFGF in vitro using a modified EST
      protocol. Sequentially, we further investigated how bFGF impact the different
      tissue-special genes and proteins expressions during the differentiation of
      murine ES cells in vitro and attempt to reveal the effects of bFGF on
      differentiation processes. This analysis was focused on key tissue- and stage
      specific genes involved in ectodermal, mesodermal, and endodermal
      differentiation, including ectodermal-specific gene Nestin, Oligo2 and Syn,
      mesodermal-specific gene MHC and MyoD, and endodermal-specific gene GATA6, TTR
      and ALB, as well as undifferentiated gene Sox-2 and Oct-4. The results
      demonstrate that bFGF could promote expression of ectodermal-specific genes and
      protein, but suppress the expressions of endoderm-specific and some mesoderm
      specific gene and protein. A conclusion can be drawn that bFGF exhibits weak
      embryotoxicity and mainly promotes ES cell differentiation towards the ectodermal
      lineages but suppress differentiation into endoderm lineages. These opposing
      effects of bFGF on the embryonic development of the three germ layers may be
      related to its weak embryotoxic potential. More specifically, inhibition of
      expression of the endodermal-specific markers transthyretin (TTR), and albumin
      (ALB) by bFGF may be of more value in detecting the embryotoxic potential of
      bFGF.

PMID- 24559482
TI  - Aging mesenchymal stem cells fail to protect because of impaired migration and
      antiinflammatory response.
AB  - RATIONALE: Aging is characterized by functional impairment and reduced capacity
      to respond appropriately to environmental stimuli and injury. With age, there is
      an increase in the incidence and severity of chronic and acute lung diseases.
      However, the relationship between age and the lung's reduced ability to repair is
      far from established and necessitates further research in the field. OBJECTIVES:
      Little is currently known about age-related phenomena in mesenchymal stem cells
      (MSCs). On account of their ability to protect the endothelium and the alveolar
      epithelium through multiple paracrine mechanisms, we looked for adverse effects
      that aging might cause in MSC biology. Such age-related changes might partly
      account for the increased susceptibility of the aging lung to injury.
      MEASUREMENTS AND MAIN RESULTS: We demonstrated that old mice have more
      inflammation in response to acute lung injury. To investigate the causes, we
      compared the global gene expression of aged and young bone marrow-derived MSCs (B
      MSCs). Our results revealed that the expression levels of inflammatory response
      genes depended on the age of the B-MSCs. We demonstrated that the age-dependent
      decrease in expression of several cytokine and chemokine receptors is important
      for the migration and activation of B-MSCs. Finally, we showed by adoptive
      transfer of aged B-MSCs to young endotoxemic mice that aged cells lacked the
      antiinflammatory protective effect of their young counterparts. CONCLUSIONS:
      Taken together, the decreased expression of cytokine and chemokine receptors in
      aged B-MSCs compromises their protective role by perturbing the potential of B
      MSCs to become activated and mobilize to the site of injury.

PMID- 24559484
TI  - Repeated pre-syncope from increased inspired CO2 in a background of severe
      hypoxia.
AB  - We describe a case of experimentally induced pre-syncope in a healthy young man
      when exposed to increased inspired CO2 in a background of hypoxia. Acute severe
      hypoxia (FIO2=0.10) was tolerated, but adding CO2 to the inspirate caused pre
      syncope symptoms accompanied by hypotension and large reductions in both mean and
      diastolic middle cerebral artery velocity, while systolic flow velocity was
      maintained. The mismatch of cerebral perfusion pressure and vascular tone caused
      unique retrograde cerebral blood flow at the end of systole and a reduction in
      cerebral tissue oxygenation. We speculate that this occurrence of pre-syncope was
      due to hypoxia-induced inhibition of brain regions responsible for compensatory
      sympathetic activity to relative hypercapnia.

PMID- 24559485
TI  - Inhibition of metastatic tumor growth and metastasis via targeting metastatic
      breast cancer by chlorotoxin-modified liposomes.
AB  - A liposome system modified with chlorotoxin (ClTx), a scorpion venom peptide
      previously utilized for targeting brain tumors, was established. Its targeting
      efficiency and antimetastasis behavior against metastatic breast cancer highly
      expressed MMP-2, the receptor of ClTx, were investigated. 4T1, a metastatic
      breast cancer cell line derived from a murine breast tumor, was selected as the
      cell model. As results, the ClTx-modified liposomes displayed specific binding to
      4T1 as determined by flow cytometry and confocal imaging. The cytotoxicity assay
      revealed that the ClTx modification increased the toxicity compared with
      nonmodified liposomes. In addition, the modified liposomes also exhibited high in
      vivo targeting efficiency in the BALB/c mice bearing 4T1 tumors. Importantly,
      this system inhibited the growth of metastatic tumor and prevented the incidence
      of lung metastasis in mice bearing 4T1 tumors with only low systemic toxicity.
      The data obtained from the in vitro and in vivo studies confirmed that the ClTx
      modified liposomes increased the drug delivery to metastatic breast cancers. This
      study proved that the ClTx-modified liposomes had targeting ability to metastatic
      breast cancer in addition to brain cancer, and displayed an obvious
      antimetastasis effect. Generally, it may provide a promising strategy for
      metastatic breast cancer therapy. 

PMID- 24559486
TI  - Mercury exposure associated with altered plasma thyroid hormones in the declining
      western pond turtle (Emys marmorata) from California mountain streams.
AB  - Mercury (Hg) is a global threat to wildlife health that can impair many
      physiological processes. Mercury has well-documented endocrine activity; however,
      little work on the effects of Hg on the thyroid hormones triiodothyronine (T3)
      and thyroxine (T4) in aquatic wildlife exists despite the fact that it is a
      sensitive endpoint of contaminant exposure. An emerging body of evidence points
      to the toxicological susceptibility of aquatic reptiles to Hg exposure. We
      examined the endocrine disrupting potential of Hg in the western pond turtle
      (Emys marmorata), a long-lived reptile that is in decline throughout California
      and the Pacific Northwest. We measured total Hg (THg) concentrations in red blood
      cells (RBCs) and plasma T3 and T4 of turtles from several locations in California
      that have been impacted by historic gold mining. Across all turtles from all
      sites, the geometric mean and standard error THg concentration was 0.805 +/-
      0.025 MUg/g dry weight. Sampling region and mass were the strongest determinants
      of RBC THg. Relationships between RBC THg and T3 and T4 were consistent with Hg
      induced disruption of T4 deiodination, a mechanism of toxicity that may cause
      excess T4 levels and depressed concentrations of biologically active T3. 

PMID- 24559488
TI  - Anxiety sensitivity and risk-taking behavior.
AB  - High trait anxiety has been linked with risk-avoidant decision-making, though
      little is known regarding the specific facets of anxiety contributing to this
      negative association. Anxiety sensitivity (AS), a transdiagnostic vulnerability
      factor for anxiety-related pathology, may be particularly relevant to risk
      decision-making given that risk-taking behaviors generate heightened somatic
      arousal and produce many of the sensations feared by individuals with high AS.
      Two studies were conducted to investigate the relation between AS and risk
      decision-making. In the first study, 268 undergraduate students completed a
      series of questionnaires that included measures of AS and gambling behaviors.
      Significant negative correlations were observed between AS and several gambling
      related risk-taking activities, and hierarchical multiple regression analyses
      indicated that AS scores added significant incremental validity in predicting
      risk-taking over and above demographic variables, negative affect, and trait
      anxiety. In the second study, 43 participants who had screened for high (n=20) or
      low (n=23) AS completed the Iowa gambling task, a behavioral measure of risk
      taking. Results indicated that, when placed under conditions of risk, individuals
      with high AS engaged in significantly less risk-taking than their low AS
      counterparts. The implications of these findings and potential directions for
      future research are discussed.

PMID- 24559487
TI  - Effect of intermittent aerobic exercise on sleep quality and sleep disturbances
      in patients with rheumatoid arthritis - design of a randomized controlled trial.
AB  - BACKGROUND: Poor sleep is prevalent in patients with systemic inflammatory
      disorders, including rheumatoid arthritis, and, in addition to fatigue, pain,
      depression and inflammation, is associated with an increased risk of co-morbidity
      and all-cause mortality. Whereas non-pharmacological interventions in patients
      with rheumatoid arthritis have been shown to reduce pain and fatigue, no
      randomized controlled trials have examined the effect of non-pharmacological
      interventions on improvement of sleep in patients with rheumatoid arthritis. The
      aim of this trial was to evaluate the efficacy of an intermittent aerobic
      exercise intervention on sleep, assessed both objectively and subjectively in
      patients with rheumatoid arthritis. METHODS/DESIGN: A randomized controlled trial
      including 44 patients with rheumatoid arthritis randomly assigned to an exercise
      training intervention or to a control group. The intervention consists of 18
      session intermittent aerobic exercise training on a bicycle ergometer three times
      a week. Patients are evaluated according to objective changes in sleep as
      measured by polysomnography (primary outcome). Secondary outcomes include changes
      in subjective sleep quality and sleep disturbances, fatigue, pain, depressive
      symptoms, physical function, health-related quality of life and cardiorespiratory
      fitness. DISCUSSION: This trial will provide evidence of the effect of
      intermittent aerobic exercise on the improvement of sleep in patients with
      rheumatoid arthritis, which is considered important in promotion of health and
      well-being. As such, the trial meets a currently unmet need for the provision of
      non-pharmacological treatment initiatives of poor sleep in patients with
      rheumatoid arthritis. TRIAL REGISTRATION: ClinicalTrials.gov Identifier:
      NCT01966835.

PMID- 24559491
TI  - Palladium-catalyzed Suzuki cross-coupling of arylhydrazines via C-N bond
      cleavage.
AB  - The first example of Pd-catalyzed Suzuki cross-coupling of readily available
      arylhydrazines with arylboronic acids via C-N bond cleavage was developed under
      air, affording various biaryl compounds with broad substrate applicability and
      moderate to good yields. Moreover, the rigorous exclusion of air/moisture is not
      required in these transformations. Thus, the protocol represents a simple and
      efficient procedure to access biaryl compounds. 

PMID- 24559490
TI  - Differences in trunk accelerometry between frail and non-frail elderly persons in
      functional tasks.
AB  - BACKGROUND: Physical conditions through gait and other functional task are
      parameters to consider for frailty detection. The aim of the present study is to
      measure and describe the variability of acceleration, angular velocity and trunk
      displacement in the ten meter Extended Timed Get-Up-and-Go test in two groups of
      frail and non-frail elderly people through instrumentation with the iPhone4(r)
      smartphone. Secondly, to analyze the differences and performance of the variance
      between the study groups (frail and non-frail).This is a cross-sectional study of
      30 subjects aged over 65 years, 14 frail subjects and 16 non-frail subjects.
      RESULTS: The highest difference between groups in the Sit-to-Stand and Stand-to
      Sit subphases was in the y axis (vertical vector). The minimum acceleration in
      the Stand-to-Sit phase was -2.69 (-4.17/-0.96) m/s2 frail elderly versus -8.49 (
      12.1/-5.23) m/s2 non-frail elderly, p < 0.001. In the Gait Go and Gait Come
      subphases the biggest differences found between the groups were in the vertical
      axis: -2.45 (-2.77/-1.89) m/s2 frail elderly versus -5.93 (-6.87/-4.51) m/s2 non
      frail elderly, p < 0.001. Finally, with regards to the turning subphase, the
      statistically significant differences found between the groups were greater in
      the data obtained from the gyroscope than from the accelerometer (the gyroscope
      data for the mean maximum peak value for Yaw movement angular velocity in the
      frail elderly was specifically 25.60 degrees /s, compared to 112.8 degrees /s for
      the non-frail elderly, p < 0.05). CONCLUSIONS: The inertial sensor fitted in the
      iPhone4(r) is capable of studying and analyzing the kinematics of the different
      subphases of the Extended Timed Up and Go test in frail and non-frail elderly
      people. For the Extended Timed Up and Go test, this device allows more sensitive
      differentiation between population groups than the traditionally used variable,
      namely time.

PMID- 24559489
TI  - Escherichia coli bacteraemia in adults: age-related differences in clinical and
      bacteriological characteristics, and outcome.
AB  - To explore the specificities of Escherichia coli bacteraemia in the elderly, the
      demographic, clinical and bacteriological characteristics and in-hospital
      mortality rate of 'young' (18-64 years, n = 395), 'old' (65-79 years, n = 372)
      and 'very old' (?80 years, n = 284) adult patients of the multicentre COLIBAFI
      cohort study were compared. Clinical and bacteriological risk factors for death
      were jointly identified by logistic regression and multivariate analysis within
      each group. 'Young' and 'old' patients had more comorbidities than 'very old'
      patients (comorbidity score: 1.5 +/- 1.3 and 1.6 +/- 1.2 vs. 1.2 +/- 1.2,
      respectively; P < 0.001), and were more frequently nosocomially infected (22.3%
      and 23.8% vs. 8.8%, respectively; P < 0.001). 'Old' patients had the poorest
      prognosis (death rate: 16.4% vs.10.4% for 'young' and 12.0% for 'very old'
      patients, respectively; P = 0.039). Risk factors for death were age group
      specific, suggesting a host-pathogen relationship evolving with age.

PMID- 24559492
TI  - Communication and cybercoping: coping with chronic illness through communicative
      action in online support networks.
AB  - Computer-mediated communication, specifically blogs, has expanded the range of
      the communicative action of patients with chronic disease from information
      seeking to information forwarding. The authors examine the effects of these 2
      types of communicative action on perceived affective and physical coping
      outcomes. Using a survey dataset of 254 chronic disease patients, the authors
      tested 2 models using structural equation modeling: first, the effects of
      communicative action about chronic illness on coping outcomes; and second, the
      mediating role of emotion-focused and problem-focused coping processes. Findings
      indicate overall positive effects of communicative action on coping processes and
      outcomes, yet with different magnitudes of effects depending on the dimensions of
      communication behavior, the coping process, and outcome. Implications for
      patients and health care providers are discussed. 

PMID- 24559493
TI  - Photoinitiated synthesis of self-assembled vesicles.
AB  - The aqueous photochemistry of 2-oxooctanoic acid (a single-tailed surfactant)
      results in the synthesis of a double-tailed surfactant product followed by
      spontaneous self-assembly into vesicles. The photochemical mechanism is detailed
      here, and the reaction products are identified using mass spectrometry. Then, the
      self-assembled vesicles are characterized using dynamic light scattering,
      fluorescence microscopy, and NMR. Further, their stability over time and in the
      presence of MgCl2 salt is demonstrated. This work contributes to membrane
      evolution through the provision of a prebiotic route for the synthesis of
      plausible membrane components and subsequent self-assembly of a primitive
      enclosure. 

PMID- 24559494
TI  - High-resolution crystal structure of the recombinant diheme cytochrome c from
      Shewanella baltica (OS155).
AB  - Multiheme cytochromes c (cyts c) are c-type cyts characterized by non-standard
      structural and spectroscopic properties. The relative disposition of the heme
      cofactors in the core of these proteins is conserved and they can be classified
      from their geometry in two main groups. In one group the porphyrin planes are
      arranged in a perpendicular fashion, while in the other they are parallel.
      Orientation of the heme groups is a key factor that regulates the intramolecular
      electron transfer pathway. A 16.5 kDa diheme cyt c, isolated from the bacterium
      Shewanella baltica OS155 (Sb-DHC), was cloned and expressed in E. coli and its
      structure was investigated by X-ray crystallography. Using high-resolution data
      (1.14 A) collected at ELETTRA (Trieste), the crystal structure, with an
      orthorhombic cell (a = 40.81, b = 42.97, c = 82.07 A), was solved using the
      homologous diheme from Rhodobacter sphaeroides (Rs-DHC) as the initial model. The
      electron density map of the refined structure (Rfact of 13.8% and Rfree of 15.4%)
      shows a two domain structure connected by a central unstructured region (N72
      G87). The Sb-DHC, like its homologue (Rs-DHC), folds into a new cyt c class: the
      N-terminal globular domain, with its three alpha-helices, belongs to class I of c
      type cyts, while the C-terminal domain includes a rare pi-helix. The metal centre
      of the c-type heme groups is axially coordinated by two His residues and it is
      covalently bound to the protein through two Cys bonds.

PMID- 24559495
TI  - The effect of smoking on DNA methylation of peripheral blood mononuclear cells
      from African American women.
AB  - BACKGROUND: Regular smoking is associated with a wide variety of syndromes with
      prominent inflammatory components such as cancer, obesity and type 2 diabetes.
      Heavy regular smoking is also associated with changes in the DNA methylation of
      peripheral mononuclear cells. However, in younger smokers, inflammatory
      epigenetic findings are largely absent which suggests the inflammatory
      response(s) to smoking may be dose dependent. To help understand whether
      peripheral mononuclear cells have a role in mediating these responses in older
      smokers with higher cumulative smoke exposure, we examined genome-wide DNA
      methylation in a group of well characterized adult African American subjects
      informative for smoking, as well as serum C-reactive protein (CRP) and
      interleukin-6 receptor (IL6R) levels. In addition, complementary bioinformatic
      analyses were conducted to delineate possible pathways affected by long-term
      smoking. RESULTS: Genome-wide DNA methylation analysis with respect to smoking
      status yielded 910 significant loci after Benjamini-Hochberg correction. In
      particular, two loci from the AHRR gene (cg05575921 and cg23576855) and one locus
      from the GPR15 gene (cg19859270) were identified as highly significantly
      differentially methylated between smokers and non-smokers. The bioinformatic
      analyses showed that long-term chronic smoking is associated with altered
      promoter DNA methylation of genes coding for proteins mapping to critical sub
      networks moderating inflammation, immune function, and coagulation. CONCLUSIONS:
      We conclude that chronic regular smoking is associated with changes in peripheral
      mononuclear cell methylation signature which perturb inflammatory and immune
      function pathways and may contribute to increased vulnerability for complex
      illnesses with inflammatory components.

PMID- 24559496
TI  - Neuronal growth on L- and D-cysteine self-assembled monolayers reveals neuronal
      chiral sensitivity.
AB  - Studying the interaction between neuronal cells and chiral molecules is
      fundamental for the design of novel biomaterials and drugs. Chirality influences
      all biological processes that involve intermolecular interaction. One common
      method used to study cellular interactions with different enantiomeric targets is
      the use of chiral surfaces. Based on previous studies that demonstrated the
      importance of cysteine in the nervous system, we studied the effect of L- and D
      cysteine on single neuronal growth. L-Cysteine, which normally functions as a
      neuromodulator or a neuroprotective antioxidant, causes damage at elevated
      levels, which may occur post trauma. In this study, we grew adult neurons in
      culture enriched with L- and D-cysteine as free compounds or as self-assembled
      monolayers of chiral surfaces and examined the effect on the neuronal morphology
      and adhesion. Notably, we have found that exposure to the L-cysteine enantiomer
      inhibited, and even prevented, neuronal attachment more severely than exposure to
      the D-cysteine enantiomer. Atop the L-cysteine surfaces, neuronal growth was
      reduced and degenerated. Since the cysteine molecules were attached to the
      surface via the thiol groups, the neuronal membrane was exposed to the molecular
      chiral site. Thus, our results have demonstrated high neuronal chiral
      sensitivity, revealing chiral surfaces as indirect regulators of neuronal cells
      and providing a reference for studying chiral drugs.

PMID- 24559497
TI  - Novel PEG-grafted nanostructured lipid carrier for systematic delivery of a
      poorly soluble anti-leukemia agent Tamibarotene: characterization and evaluation.
AB  - Tamibarotene (Am80), a poorly water-soluble drug for the treatment of acute
      promyelocytic leukemia (APL), loaded nanostructured lipid carrier (Am80-NLC) was
      developed and characterized previously. The purpose of the present work was to
      develop PEGylated nanostructured lipid carrier (PEG-NLC) for intravenous delivery
      of Am80, with the aim to further extend the circulation in blood and decrease the
      adverse events. Am80-loaded PEG-NLC (Am80-PEG-NLC) modified with PEG-40 stearate
      (PEG40-SA, molecular weight 2000 Da) was formulated by the method of melt
      emulsification and low temperature-solidification technique. Am80-NLC was
      developed as well as control. Based on the optimized results of single-factor
      screening experiment, the average drug entrapment efficiency, the mean particle
      size, and zeta potential of Am80-NLC and Am80-PEG-NLC were found to be 89.8
      94.3%, 178.9-201.6 nm, and -37.74 to -20.1 mV, respectively. In vitro drug
      release of Am80-NLC and Am80-PEG-NLC possessed a sustained release characteristic
      and their release behavior was in accordance with the Ritger-Peppas equation. In
      vivo, after intravenous (i.v.) injection to rats, the mean residence time (MRT)
      of Am80-PEG-NLC group was significantly prolonged and the AUC value was improved
      as well compared with the Am80-NLC group. Furthermore, the biodistribution in
      mice showed that Am80-PEG-NLC preferentially decreased the accumulation of Am80
      in kidney and increased the drug concentration in brain after i.v. injection. In
      conclusion, Am80-PEG-NLC may be a potential delivery system for Am80 in the
      treatment of APL.

PMID- 24559498
TI  - Evaluation of a virtual reality prospective memory task for use with individuals
      with severe traumatic brain injury.
AB  - The current study aimed to evaluate the sensitivity, convergent validity and
      ecological validity of a newly developed virtual reality prospective memory (PM)
      task (i.e., the Virtual Reality Shopping Task; VRST) for use with individuals
      with traumatic brain injury (TBI). Thirty individuals with severe TBI and 24
      uninjured adults matched on age, gender and education level were administered the
      VRST, a lexical decision PM task (LDPMT), an index of task-friendliness and a
      cognitive assessment battery. Significant others rated disruptions in the TBI
      participants' occupational activities, interpersonal relationships and
      independent living skills. The performance of the TBI group was significantly
      poorer than that of controls on event-based PM as measured by the LDPMT, and on
      time- and event-based PM as measured by the VRST. Performance on the VRST
      significantly predicted significant others' ratings of patients' occupational
      activities and independent living skills. The VRST was rated as significantly
      more reflective of an everyday activity, interesting and was afforded a higher
      recommendation than the LDPMT. For the TBI group, event and total PM performance
      on the VRST significantly correlated with performance on measures of mental
      flexibility and verbal fluency, and total PM performance correlated with verbal
      memory. These results provide preliminary but promising evidence of the
      sensitivity, as well as the convergent and ecological validity of the VRST. 

PMID- 24559499
TI  - Ligand-directed conformation of inorganic-organic molecular capsule and cage.
AB  - Four new inorganic-organic hybrids, namely,
      (NH4)3H3[AsMo6O21(O2CC6H4NH2)3].8.5H2O (1),
      (NH4)16H3[(AsMo6O21)3(O2CCH2CO2)5].18H2O (2),
      (NH4)11H[(AsMo6O21)2{O2C(CH2)6CO2}3].8H2O (3), and
      (NH4)18H6[(AsMo6O21)4{C6H3(CO2)3}4].24.5H2O (4), were synthesized by reaction of
      As2O3 with (NH4)6Mo7O24.4H2O and organic components in aqueous medium. All of the
      four hybrids feature a common {AsMo6} unit composed of a six-membered MoO6
      octahedral ring capped by one {AsO3} trigonal pyramid. Although these hybrids
      exhibit similar chemical formula, their structures are monomer, dimer (capsule),
      trimer, and tetramer (cage), respectively, depending upon the nature of
      carboxylic acids. Also, the assembly processes appear to be highly versatile and
      sensitive to the inherent nature of carboxylic acids, which direct the assemblies
      toward construction of POM clusters and participate directly to their
      stabilization. In addition, successful isolation of these hydrids shows that it
      would be possible to achieve a variety of structural predesign in this inorganic
      organic system by means of a ligand design route based on the interplay between
      the organic molecules and polyoxometalates (POMs). 

PMID- 24559500
TI  - Contribution of rating scales to intervention for executive dysfunction.
AB  - Executive dysfunction is present in children, adolescents, and adults with a wide
      range of clinical conditions. A growing body of literature has demonstrated the
      usefulness of rating scales designed to gauge executive functioning in everyday
      life. In this article, we discuss evidence supporting the use of such rating
      scales to assess intervention outcome, how they may inform development of
      interventions, and how comparing rater perspectives can assess awareness of
      cognitive dysfunction. We provide an example of how an executive function rating
      scale helped define intervention targets and measured outcomes in a recently
      published real-world intervention for children with autism spectrum disorder.
      Rating scales of executive function provide valuable information with respect to
      treatment planning and assessment of intervention outcome.

PMID- 24559501
TI  - Catalytic anions embedded into avidin: importance of their chirality and the
      chiral environment on the stereocontrol of the aldol reaction.
AB  - Several catalytic anions bearing a pseudo-dipeptide scaffold, in combination with
      a biotinylated imidazolium cation, were prepared. The assembly of these salts
      with avidin resulted in the formation of stable biohybrid catalysts, active in
      ionic liquid/aqueous media for the aldol reaction. By using natural and non
      natural amino alcohols as "side chains" for the proline derivative anion, we
      studied the cooperativity between the anion and its position in avidin. Taking
      advantage of the large freedom of movement of the anion inside avidin, we also
      investigated the substrate scope of this type of biohybrid catalyst. 

PMID- 24559502
TI  - Infrared photodissociation spectroscopy of iron nitrosyl cation complexes:
      Fe(NO)n+ (n = 1-5).
AB  - Infrared spectra of mass-selected mononuclear iron nitrosyl cations Fe(NO)n(+)
      with n = 1-5 and their argon tagged complexes are measured via infrared
      photodissociation spectroscopy in the nitrosyl stretching frequency region in the
      gas phase. The structures are established by comparison of the experimental
      spectra with the simulated spectra derived from density functional calculations.
      Two IR active bands were observed for the argon-tagged Fe(NO)2(+) and Fe(NO)3(+)
      complexes, consistent with theoretical predictions that these complexes have bent
      C(2v) and nonplanar C(3v) symmetry, respectively. The Fe(NO)4(+) complex was
      characterized to have a completed coordination sphere with 17 electrons
      containing a bent one-electron NO ligand and three three-electron NO ligands. The
      Fe(NO)5(+) complex was determined to involve a Fe(NO)4(+) core ion that is
      solvated by an external NO molecule.

PMID- 24559503
TI  - Recent trends in the epidemiology of shigellosis in Israel.
AB  - We provide an update on the epidemiology of shigellosis in Israel using data
      generated by a sentinel laboratory-based surveillance network for the period 1998
      2012. The average annual incidence of culture-proven shigellosis was 97/100 000.
      We estimated that each case of shigellosis accounted for 25 cases in the
      community indicating the high burden of disease. Orthodox Jewish communities,
      living in highly crowded conditions and with a high number of children aged <5
      years were the epicentre of country-wide biennial propagated epidemics of S.
      sonnei shigellosis. S. flexneri was the leading Shigella serogroup in Israeli
      Arabs. S. flexneri 2a and S. flexneri 6 alternated as the most common serotypes.
      Both S. sonnei and S. flexneri isolates showed high rates of resistance to
      ampicillin and trimethoprim/sulfamethoxazole and very low rates of resistance to
      quinolones and third-generation cephalosporins. Shigellosis due to S. sonnei
      conferred 81% (95% confidence interval 69-89) protection against the homologous
      Shigella serotype when epidemic exposure re-occurred 2 years later. These data
      are of value in the process of Shigella vaccine development.

PMID- 24559504
TI  - Exploring first grade medical students' professional identity using metaphors:
      implications for medical curricula.
AB  - BACKGROUND: Although professional identity development is an important concept in
      medical education, the process has not been well-investigated from a student
      perspective. PURPOSE: This study examines the metaphorical images formulated by
      first grade medical students in Turkey to describe physicians in the context of
      establishing a professional identity, along with its limitations. METHOD:
      Participants (N=148) completed the prompt: A physician is like _____ because
      _____ to indicate their conceptualizations of physician. The data were analyzed
      both qualitatively and quantitatively. RESULTS: Altogether, 71 well-articulated
      metaphorical images were identified - comprising six conceptual themes.
      CONCLUSIONS: While subject to some limitations, the use of metaphors to formulate
      and describe professional identities can be helpful in reflecting the personal
      beliefs and values of matriculants to medical school, as well as providing some
      guidance and feedback to curriculum development efforts.

PMID- 24559505
TI  - How does the quality of life and the underlying biochemical indicators correlate
      with the performance in academic examinations in a group of medical students of
      Sri Lanka?
AB  - BACKGROUND: Individual variation of examination performance depends on many
      modifiable and non-modifiable factors, including pre-examination anxiety. Medical
      students' quality of life (QoL) and certain biochemical changes occurring while
      they are preparing for examinations has not been explored. PURPOSE: We
      hypothesize that these parameters would determine the examination performance
      among medical students. METHODS: Fourth-year medical students (n=78) from the
      University of Ruhuna, Sri Lanka, were invited. Their pre- and post-exam status of
      QoL, using the World Health Organization Quality of Life (WHOQOL-BREF)
      questionnaire, and the level of biochemical marker levels (i.e., serum levels of
      thyroid profile including thyroglobulin, cortisol and ferritin) were assessed.
      Differences between the scores of QoL and serum parameters were compared with
      their performance at the examination. RESULTS: The mean QoL score was
      significantly lower at pre-exam (56.19+/-8.1) when compared with post-exam
      (61.7+/-7.1) levels (p<0.001). The median serum TSH level prior to the exam (0.9
      mIU/L; interquartile range 0.74-1.4 mIU/L) was significantly lower (p=0.001) when
      compared with the level after the exam (median of 2.7 mIU/L; IQR 1.90-3.60). The
      mean+/-SD fT4 level was significantly higher before the exam (19.48+/-0.4 pmol/L
      at study entry vs. 17.43+/-0.3 pmol/L after the exam; p<0.001). Median serum
      ferritin (SF) level prior to the exam (43.15 (23.5-63.3) ug/L) was significantly
      lower (p<=0.001) when compared with after-exam status (72.36 (49.9-94.9) ug/L).
      However, there was no difference in mean serum cortisol levels (16.51+/-0.7 at
      pre-exam and 15.88+/-0.7 at post-exam, respectively; p=0.41). CONCLUSIONS:
      Students had higher fT4 and low ferritin levels on pre-exam biochemical
      assessment. It was evident that students who perform better at the examination
      had significantly higher QoL scores at each domain tested through the
      questionnaire (Physical health, Psychological, Social interaction and
      Environment). The higher the QoL scores, the better the grades were. It was also
      found that students who failed exhibited profound differences in the QoL score.

PMID- 24559506
TI  - Suicide prevention in Spain: an uncovered clinical need.

PMID- 24559507
TI  - Three-dimensional evaluation of the relationship between jaw divergence and
      facial soft tissue dimensions.
AB  - OBJECTIVE: To evaluate the relationship between mandibular divergence and
      vertical and transverse dimensions of the face. MATERIALS AND METHODS: A sample
      was recruited from the orthodontic clinic of the University of Otago, New
      Zealand. The recruited participants (N  =  60) were assigned to three different
      groups based on the mandibular plane angle (hyperdivergent, n  =  20;
      normodivergent, n  =  20; and hypodivergent, n  =  20). The sample consisted of
      31 females and 29 males, with a mean age of 21.1 years (SD +/- 5.0). Facial scans
      were recorded for each participant using a three-dimensional (3D) white-light
      scanner and then merged to form a single 3D image of the face. Vertical and
      transverse measurements of the face were assessed from the 3D facial image.
      RESULTS: The hyperdivergent sample had a significantly larger total and lower
      anterior facial height than the other two groups (P < .05), although no
      difference was found for the middle facial height (P > .05). Similarly, there
      were no significant differences in the transverse measurements of the three study
      groups (P > .05). Both gender and body mass index (BMI) had a greater influence
      on the transverse dimension. CONCLUSIONS: Hyperdivergent facial types are
      associated with a long face but not necessarily a narrow face. Variations in
      facial soft tissue vertical and transversal dimensions are more likely to be due
      to gender. Body mass index has a role in mandibular width (GoGo) assessment.

PMID- 24559508
TI  - Role of polycystin-1 in bone remodeling: orthodontic tooth movement study in
      mutant mice.
AB  - OBJECTIVE: To test the hypothesis that polycystin-1 (PC1) is involved in
      orthodontic tooth movement as a mechanical sensor. MATERIALS AND METHODS: The
      response to force application was compared between three mutant and four wild
      type 7-week-old mice. The mutant mice were PC1/Wnt1-cre, lacking PC1 in the
      craniofacial region. An orthodontic closed coil spring was bonded between the
      incisor and the left first molar, applying 20 g of force for 4 days. Micro
      computed tomography, hematoxylin and eosin staining, and tartrate-resistent acid
      phosphatase (TRAP) staining were used to study the differences in tooth movement
      among the groups. RESULTS: In the wild-type mice the bonded molar moved mesially,
      and the periodontal ligament (PDL) was compressed in the compression side. The
      compression side showed a hyalinized zone, and osteoclasts were identified there
      using TRAP staining. In the mutant mice, the molar did not move, the incisor
      tipped palatally, and there was slight widening of the PDL in the tension area.
      Osteoclasts were not seen on the bone surface or on the compression side.
      Osteoclasts were only observed on the other side of the bone-in the bone marrow.
      CONCLUSIONS: These results suggest a difference in tooth movement and osteoclast
      activity between PC1 mutant mice and wild-type mice in response to orthodontic
      force. The impaired tooth movement and the lack of osteoclasts on the bone
      surface in the mutant working side may be related to lack of signal from the PDL
      due to PC1 deficiency.

PMID- 24559509
TI  - Effects of eye drops containing a mixture of omega-3 essential fatty acids and
      hyaluronic acid on the ocular surface in desiccating stress-induced murine dry
      eye.
AB  - PURPOSE: To investigate the efficacy of the topical application of omega-3
      essential fatty acids (EFAs) and hyaluronic acid (HA) mixtures in a mouse model
      of experimental dry eye (EDE). METHODS: Eye drops consisting of 0.1% HA, 0.02%,
      or 0.2% omega-3 EFAs alone and mixture of 0.02%, or 0.2% omega-3 EFAs and 0.1% HA
      were applied in desiccating stress-induced murine dry eye. Corneal irregularity
      scores and fluorescein staining scores were measured 5 and 10 days after
      treatment. Levels of interleukin (IL)-1beta, -17, and interferon gamma-induced
      protein (IP)-10 were measured in the conjunctiva at 10 days using a multiplex
      immunobead assay. The concentrations of hexanoyl-lys (HEL) and 4-hydroxynonenal
      (4-HNE) in conjunctiva tissue were measured with enzyme-linked immunosorbent
      assays. RESULTS: Mice treated with the mixture containing 0.2% omega-3 EFAs
      showed a significant improvement in corneal irregularity scores and corneal
      fluorescein staining scores compared with EDE, HA, 0.02% or 0.2% omega-3 EFAs
      alone, and 0.02% omega-3 EFAs mixture-treated mice. A significant decrease in the
      levels of IL-1beta, -17, and IP-10 were observed in the 0.2% EFAs mixture-treated
      group, compared with the other groups. In the mice treated with the mixture
      containing 0.2% omega-3 EFAs, the concentration of 4-HNE was also lower than the
      other groups. Although 0.2% omega-3 EFAs alone group also had a significant
      improvement in corneal irregularity scores and IL-17, IL-10, and 4 HNE levels
      compared with the other groups, the efficacy was lower than 0.2% omega-3 mixture
      group. CONCLUSIONS: Topically applied eye drops containing a mixture of omega-3
      EFAs and HA could improve corneal irregularity and corneal epithelial barrier
      disruption, and decrease inflammatory cytokines and oxidative stress markers on
      the ocular surface. Topical omega-3 EFAs and HA mixture may have a greater
      therapeutic effect on clinical signs and inflammation of dry eye compared with HA
      artificial tears.

PMID- 24559511
TI  - Tracing the fates of site-specifically introduced DNA adducts in the human
      genome.
AB  - We developed a system for tracing DNA adducts in targeted mutagenesis (TATAM) and
      investigated the prevalence and types of consequent mutations. Targeted
      mutagenesis methods site-specifically replace endogenous DNA bases with bases
      carrying synthetic adducts using targeting vectors. The TATAM system was enabled
      by introduction of site-specific DNA double strand breaks (DSB), which strongly
      enhanced targeting efficiency through homologous recombination (HR), and a new
      polymerase chain reaction-based technique, which gives high yields of the target
      vectors carrying DNA adducts. Human lymphoblastoid TSCER122 cells are compound
      heterozygous for the thymidine kinase gene (TK-/-), and have a homing
      endonuclease I-SceI site in intron 4 of the TK gene. The TATAM system enabled
      targeting of the TK- allele with the I-SceI site using a synthetic TK+ allele
      containing an 8-oxo-7,8-dihydroguanine (8-oxoG) adduct, a typical product of
      oxidative DNA damage. The targeted clones (TK+/-) were then isolated by drug
      selection. Site-specific HR for DSB induced by I-SceI improved targeted
      integration of the synthetic allele by five orders of magnitude (from 10(-7) to
      10(-2)). Subsequent analyses of approximately 800 target clones revealed that 8
      oxoG was restored to G in 86% clones, probably reflecting base excision repair or
      translesion synthesis without mutation. Lesions of the remaining clones (14%)
      were associated with mutations. The mutation spectrum corresponded closely with
      that of oxidative DNA damage inducers reported, in which G:C to T:A transversions
      (5.9%) were predominant. Over-expression of MutY homologs in cells, which
      prevents G:C to T:A transversions by removing 8-oxoG:A mispairing, significantly
      decreased the frequency of mutations to 2.6%, indicating that the 8-oxoG adducts
      introduced by the TATAM system are processed in the same manner as those
      generated by oxidative DNA damage. 

PMID- 24559510
TI  - Interaction of apurinic/apyrimidinic endonuclease 2 (Apn2) with Myh1 DNA
      glycosylase in fission yeast.
AB  - Oxidative DNA damage is repaired primarily by the base excision repair (BER)
      pathway in a process initiated by removal of base lesions or mismatched bases by
      DNA glycosylases. MutY homolog (MYH, MUTYH, or Myh1) is a DNA glycosylase which
      excises adenine paired with the oxidative lesion 8-oxo-7,8-dihydroguanine (8
      oxoG, or G degrees ), thus reducing G:C to T:A mutations. The resulting
      apurinic/apyrimidinic (AP) site is processed by an AP-endonuclease or a
      bifunctional glycosylase/lyase. We show here that the major Schizosaccharomyces
      pombe AP endonuclease, Apn2, binds to the inter-domain connector located between
      the N- and C-terminal domains of Myh1. This Myh1 inter-domain connector also
      interacts with the Hus1 subunit of the Rad9-Rad1-Hus1 checkpoint clamp.
      Mutagenesis studies indicate that Apn2 and Hus1 bind overlapping but different
      sequence motifs on Myh1. Mutation on I(261) of Myh1 reduces its interaction with
      Hus1, but only slightly attenuates its interaction with Apn2. However, E(262) of
      Myh1 is a key determinant for both Apn2 and Hus1 interactions. Like human APE1,
      Apn2 has 3'-phosphodiesterase activity. However, unlike hAPE1, Apn2 has a weak AP
      endonuclease activity which cleaves the AP sites generated by Myh1 glycosylase.
      Functionally, Apn2 stimulates Myh1 glycosylase activity and Apn2
      phosphodiesterase activity is stimulated by Myh1. The cross stimulation of Myh1
      and Apn2 enzymatic activities is dependent on their physical interaction. Thus,
      Myh1 and Apn2 constitute an initial BER complex. 

PMID- 24559512
TI  - Association of antitumor antibiotic Mithramycin with Mn2+ and the potential
      cellular targets of Mithramycin after association with Mn2+.
AB  - Mithramycin (MTR), an aureolic acid group of antitumor antibiotic is used for the
      treatment of several types of tumors. We have reported here the association of
      MTR with an essential micronutrient, manganese (Mn(2+)). Spectroscopic methods
      have been used to characterize and understand the kinetics and mechanism of
      complex formation between them. MTR forms a single type of complex with Mn(2+) in
      the mole ratio of 2:1 [MTR: Mn(2+)] via a two step kinetic process. Circular
      dichroism (CD) spectroscopic study indicates that the complex [(MTR)2 Mn(2+)] has
      a right-handed twist conformation similar in structure with the complexes
      reported for Mg(2+) and Zn(2+). This conformation allows binding via minor groove
      of DNA with (G, C) base preference during the interaction with double-stranded B
      DNA. Using absorbance, fluorescence, and CD spectroscopy we have shown that
      [(MTR)2 Mn(2+)] complex binds to double-stranded DNA with an apparent
      dissociation constant of 32 MUM and binding site size of 0.2 (drug/nucleotide).
      It binds to chicken liver chromatin with apparent dissociation constant value 298
      MUM. Presence of histone proteins in chromatin inhibits the accessibility of the
      complex for chromosomal DNA. We have also shown that MTR binds to Mn(2+)
      containing metalloenzyme manganese superoxide dismutase from Escherichia coli.

PMID- 24559513
TI  - The Escherichia coli O157:H7 bovine rumen fluid proteome reflects adaptive
      bacterial responses.
AB  - BACKGROUND: To obtain insights into Escherichia coli O157:H7 (O157) survival
      mechanisms in the bovine rumen, we defined the growth characteristics and
      proteome of O157 cultured in rumen fluid (RF; pH 6.0-7.2 and low volatile fatty
      acid content) obtained from rumen-fistulated cattle fed low protein content
      "maintenance diet" under diverse in vitro conditions. RESULTS: Bottom-up
      proteomics (LC-MS/MS) of whole cell-lysates of O157 cultured under anaerobic
      conditions in filter-sterilized RF (fRF; devoid of normal ruminal microbiota) and
      nutrient-depleted and filtered RF (dRF) resulted in an anaerobic O157 fRF-and dRF
      proteome comprising 35 proteins functionally associated with cell structure,
      motility, transport, metabolism and regulation, but interestingly, not with O157
      virulence. Shotgun proteomics-based analysis using isobaric tags for relative and
      absolute quantitation used to further study differential protein expression in
      unfiltered RF (uRF; RF containing normal rumen microbial flora) complemented
      these results. CONCLUSIONS: Our results indicate that in the rumen, the first
      anatomical compartment encountered by this human pathogen within the cattle
      gastrointestinal tract (GIT), O157 initiates a program of specific gene
      expression that enables it to adapt to the in vivo environment, and successfully
      transit to its colonization sites in the bovine GIT. Further experiments in vitro
      using uRF from animals fed different diets and with additional O157 strains, and
      in vivo using rumen-fistulated cattle will provide a comprehensive understanding
      of the adaptive mechanisms involved, and help direct evolution of novel
      modalities for blocking O157 infection of cattle.

PMID- 24559514
TI  - [Induced astigmatism after corneal suture removal after cataract surgery].
AB  - PURPOSE: To evaluate the time until astigmatic stabilization after corneal suture
      removal after cataract surgery. METHODS: A prospective study was performed on 13
      patients who had undergone cataract surgery by phacoemulsification with 2.4mm
      incision, for whom it was felt necessary to remove a corneal suture. A specular
      corneal topography was performed by OPD Scan before removal, immediately after,
      then 10, 20, 30 minutes and 15 days later. For each acquisition, the keratometric
      readings at the steepest (Kmax) and the flattest (Kmin) meridians (central at
      1.15 mm from corneal center, intermediate at 2.30 mm and peripheral at 3.30 mm)
      and the amount of corneal astigmatism were measured. RESULTS: Corneal topography
      of 13 patients was acquired. Mean age was 70 +/- 12 years. Mean time after
      cataract surgery was 23 +/- 14 days. The greatest change in Kmax occurred within
      the first minutes following suture removal for the central and intermediate
      cornea (mean variation of -4.38% and -4.59% of initial Kmax respectively, i.e. 
      2.04 D +/- 3.14 D et -2.15 D +/- 3.11 D) whereas it was observed between 0 and 10
      minutes for the peripheral area (mean 1.57% of Kmax after suture removal i.e.
      0.96 D +/- 1.85 D). Mean change in corneal astigmatism between 30 minutes and day
      15 was 0.08 D +/- 0.31 D (3.6% of baseline). When suture removal was performed
      between 7 and 10 days postoperatively, mean change was 0.16 D +/- 0.24 D, whereas
      it was 0.03 D +/- 0.34 D when performed after four weeks. CONCLUSION:
      Keratometric readings vary only slightly beyond the first 30 minutes after suture
      removal. These results suggest that the refraction could be accurately measured
      the same day as suture removal, with no additional follow-up absolutely necessary
      in order to prescribe the final spectacles.

PMID- 24559515
TI  - Femtosecond and excimer laser-assisted endothelial keratoplasty (FELEK): a new
      technique of endothelial transplantation.
AB  - PURPOSE: To describe a new technique of endothelial keratoplasty (EK) that
      improves the quality of lamellar dissection of donor cornea. METHODS: We compared
      four techniques of donor cornea preparation for lamellar dissection on 8 donor
      corneas: mechanical dissection with a microkeratome, a single femtosecond laser
      lamellar cut, a double femtosecond laser lamellar cut and combined femtosecond
      laser lamellar dissection with excimer laser surface photoablation. The quality
      of the donor cornea interface was assessed and compared using scanning electron
      microscopy (SEM), and the most satisfactory technique was employed for EK on
      three patients. The postoperative anatomic results were analyzed with anterior
      segment spectral-domain optical coherence tomography (SD-OCT) and in vivo
      confocal microscopy (IVCM). RESULTS: The smoothest stromal interface was observed
      on SEM with the combined use of femtosecond laser dissection and excimer
      photoablation. The surgical procedures performed with donor cornea prepared by a
      combination of femtosecond and excimer lasers resulted in clear corneas after 1
      month. SD-OCT showed good attachment of the endothelial graft and a
      hyperreflective interface. On IVCM, subepithelial haze, honeycomb-like activated
      keratocytes and needle-shaped particles were visible in the recipient corneal
      stroma as well as numerous hyperreflective particles on the donor-recipient
      interface. CONCLUSION: A new technique, femtosecond and excimer laser-assisted
      endothelial keratoplasty (FELEK), which refines the current limitations observed
      in Descemet-stripping automated endothelial keratoplasty (DSAEK), is described.
      Femtosecond laser dissection provides a thin and reproducible endothelial graft
      cut with a high level of safety and accuracy, while excimer photoablation yields
      a smooth, high-quality interface.

PMID- 24559516
TI  - [Post-penetrating keratoplasty glaucoma management: report of 73 cases].
AB  - PURPOSE: To report our experience in the therapeutic management of post
      penetrating keratoplasty glaucoma. INTRODUCTION: Post-penetrating keratoplasty
      (PK) glaucoma is a true threat to visual prognosis. Therapeutic modalities are
      many, but the absence of a well-defined decision tree and the variable results of
      the various techniques renders management very difficult. PATIENTS AND METHODS:
      This is a retrospective study including 73 eyes of 71 patients undergoing a
      penetrating keratoplasty. Patients who developed post-operative ocular
      hypertension were treated first with eye drops. In the case of failure, surgical
      procedures were recommended including trabeculectomy or glaucoma drainage
      devices. The intraocular pressure (IOP) assessed with applanation tonometer, side
      effects and graft failure were monitored. RESULTS: The first medical treatment
      used for all patients was a betablocker, which allowed control of intraocular
      pressure in 80.6 % of eyes. Ahmed glaucoma valve was used in two cases with
      success and without graft failure. Trabeculectomy was necessary for five
      patients, three of whom developed immunological graft rejection within 6 to 9
      months. We also observed that late ocular hypertension was statistically related
      to anatomic graft failure, independently of other preoperative factors.
      DISCUSSION AND CONCLUSION: Although hypotensive medication is still the first
      treatment for ocular hypertension after penetrating keratoplasty, a surgical
      procedure is sometimes required. Glaucoma drainage devices and trabeculectomy are
      widely practiced, leading to good outcomes, with the risk of rejection lower in
      cases involving mitomycin C. Cyclodestructive procedures should be reserved for
      surgical failures with significant visual loss.

PMID- 24559517
TI  - Preparation and in vitro/in vivo evaluation of mucosal adjuvant in situ forming
      gels with diphtheria toxoid.
AB  - Studies on preparation of in situ gel formulations containing diphtheria toxoid
      as the model active substance and their intranasal administration have been
      conducted in this study. The objective of mucosal vaccination is to stimulate
      both systemic and mucosal immune responses. In situ gel formulations were
      prepared by using, in different ratios, mixtures of Poloxamer 407 and Poloxamer
      188 polymers, which gelate in a temperature-dependent manner, and mucoadhesive
      polymers carbopol 934, hydroxypropyl methyl cellulose, hydroxypropyl cellulose or
      chitosan. Following pre-formulation studies, F1, F2, F3, F4, F5, F6 and F7
      formulations, which gelate at intervals and temperatures in accordance with nasal
      temperatures, were subjected to more comprehensive studies. For this purpose,
      organoleptic characteristics of the formulations were identified, their pH and
      mucoadhesive potencies were measured and rheological behaviors were
      characterized. Calculated amounts of diphtheria toxoid were added to formulations
      after optimization of formulations was achieved, and assay and in vitro release
      studies were carried out. Formulations coded F3 and F7 were considered to be
      superior to other formulations given the in vitro test results. Therefore, these
      formulations were tested in guinea pigs to determine immune responses, which they
      would produce following intranasal and subcutaneous administration. Absorbance
      values of ELISA tests and antibody neutralization test showed that formulations
      coded F3 and F7 were unable to stimulate adequate systemic immune response when
      either of the formulations was administered alone intranasally, whereas F7
      resulted in significantly increased neutralizing antibody titers with intranasal
      administration as a booster dose following subcutaneous administration.

PMID- 24559518
TI  - Attention and executive functions in children with epilepsy: what, why, and what
      to do.
AB  - Attention and executive function deficits are a common sequelae of many
      neurological conditions of childhood. Those with epilepsy frequently show such
      deficits, as executive dysfunction is common in all epilepsy syndromes of
      childhood. The purpose of this article is to review what is known about attention
      and executive functions, including the neurological underpinnings of these
      skills. Then, general cognitive function and dysfunction in childhood epilepsy is
      discussed with a special focus on attention and executive function impairment.
      Finally, treatment considerations for children and adolescents with these
      deficits are reviewed and future directions are discussed.

PMID- 24559520
TI  - Surfing for hip replacements: has the "internet tidal wave" led to better quality
      information.
AB  - This study aimed to determine the quality of information available on the
      internet regarding Total Hip Replacement (THR). The unique websites identified
      were categorised by type and assessed using the DISCERN score, the Journal of the
      American Medical Association (JAMA) benchmark criteria, and a novel (THR)
      specific content score. The presence of the Health On the Net (HON) code, a
      reported quality assurance marker, was noted. Commercial websites predominate.
      Governmental & Non-Profit Organizations websites attained the highest DISCERN
      score. Sites that bore the HONcode seal obtained significantly higher DISCERN and
      THR content scores than those without the certification. Physicians should
      recommend the HONcode seal to their patients as a reliable indicator of website
      quality or, better yet, refer patients to sites they have personally reviewed. 

PMID- 24559519
TI  - A systematic review and meta-synthesis of the impact of low back pain on people's
      lives.
AB  - BACKGROUND: Low back pain (LBP) is a common and costly problem that many
      interpret within a biopsychosocial model. There is renewed concern that core-sets
      of outcome measures do not capture what is important. To inform debate about the
      coverage of back pain outcome measure core-sets, and to suggest areas worthy of
      exploration within healthcare consultations, we have synthesised the qualitative
      literature on the impact of low back pain on people's lives. METHODS: Two
      reviewers searched CINAHL, Embase, PsycINFO, PEDro, and Medline, identifying
      qualitative studies of people's experiences of non-specific LBP. Abstracted data
      were thematic coded and synthesised using a meta-ethnographic, and a meta
      narrative approach. RESULTS: We included 49 papers describing 42 studies.
      Patients are concerned with engagement in meaningful activities; but they also
      want to be believed and have their experiences and identity, as someone 'doing
      battle' with pain, validated. Patients seek diagnosis, treatment, and cure, but
      also reassurance of the absence of pathology. Some struggle to meet social
      expectations and obligations. When these are achieved, the credibility of their
      pain/disability claims can be jeopardised. Others withdraw, fearful of
      disapproval, or unable or unwilling to accommodate social demands. Patients
      generally seek to regain their pre-pain levels of health, and physical and
      emotional stability. After time, this can be perceived to become unrealistic and
      some adjust their expectations accordingly. CONCLUSIONS: The social component of
      the biopsychosocial model is not well represented in current core-sets of outcome
      measures. Clinicians should appreciate that the broader impact of low back pain
      includes social factors; this may be crucial to improving patients' experiences
      of health care. Researchers should consider social factors to help develop a
      portfolio of more relevant outcome measures.

PMID- 24559521
TI  - Synovial IL-6 as inflammatory marker in periprosthetic joint infections.
AB  - We analyzed serum and synovial biomarkers of 69 patients. 31 of them suffered
      from a periprosthetic joint infection (PJI) and 38 from aseptic arthralgia after
      total joint arthroplasty. We used Receiver-Operating-Characteristic-curves to
      calculate the Area-under-the-curve (AUC), cutoff-values, positive (+LR), negative
      (-LR) and interval-Likelihood-Ratios (iLR) for predicting a PJI. The most
      significant parameter was synovial interleukin-6 (IL-6) (cutoff-value >= 30,750
      pg/ml, AUC = 0.959, SE = 90.0%, SP = 94.7%, +LR = 17.27), followed by synovial
      lactate (cutoff-value >= 8.3 mmol/l, AUC = 0.844, SE = 71.4%, SP=88.0%, +LR =
      5.95), and synovial glucose (cutoff-value <= 44 mg/dl, AUC = 0.829, SE = 79.2%,
      SP = 78.6%, +LR = 3.69). IL-6 >= 30,750 pg/ml and lactate >= 10 mmol/l make a PJI
      very likely, IL-6 <10,000pg/ml or lactate <4.3 mmol/l makes a PJI very unlikely.
      If none of these thresholds are met, physicians should use the iLR of IL-6,
      glucose and lactate to estimate the likelihood of PJI.

PMID- 24559522
TI  - Tantalum acetabular augments in one-stage exchange of infected total hip
      arthroplasty: a case-control study.
AB  - During the one-stage exchange procedure for periprosthetic joint infection (PJI)
      after total hip arthroplasty (THA), acetabular defects challenge reconstructive
      options. Porous tantalum augments are an established tool for addressing
      acetabular destruction in aseptic cases, but their utility in septic exchange is
      unknown. This retrospective case-control study presents the initial results of
      tantalum augmentation during one-stage exchange for PJI. Primary endpoints were
      rates of re-infection and short-term complications associated with this
      technique. Study patients had no higher risk of re-infection with equivalent
      durability at early follow-up with a re-infection rate in both groups of 4%. In
      conclusion, tantalum augments are a viable option for addressing acetabular
      defects in one-stage exchange for septic THA. Further study is necessary to
      assess long-term durability when compared to traditional techniques for
      acetabular reconstruction. 

PMID- 24559523
TI  - Simple and complex rule induction performance in young and older adults:
      contribution of episodic memory and working memory.
AB  - This study tested the hypothesis that part of the age-related decline in
      performance on executive function tasks is due to a decline in episodic memory.
      For this, we developed a rule induction task in which we manipulated the
      involvement of episodic memory and executive control processes; age effects and
      neuropsychological predictors of task performance were investigated. Twenty-six
      younger (mean age, 24.0; range, 19-35 years) and 27 community-dwelling older
      adults (mean age, 67.5; range, 50-91 years) participated. The neuropsychological
      predictors consisted of the performance on tests of episodic memory, working
      memory, switching, inhibition and flexibility. Performance of the older adults
      was worse for the learning and memorization of simple rules, as well as for the
      more demanding executive control condition requiring the manipulation of
      informational content. Episodic memory was the only predictor of performance on
      the simple learning and memorization task condition whereas an increase in rule
      induction complexity additionally engaged working memory processes. Together,
      these findings indicate that part of the age-related decline on rule induction
      tests may be the result of a decline in episodic memory. Further studies are
      needed that examine the role of episodic memory in other executive function tasks
      in aging.

PMID- 24559524
TI  - A daily-life-oriented intervention to improve prospective memory and goal
      directed behaviour in ageing: a pilot study.
AB  - Difficulties in the execution of goal-directed behaviours, and particularly their
      prospective memory component, can arise in ageing and have important consequences
      for autonomy. The first objective of this article is to present an intervention
      that trained older individuals who reported prospective memory or goal-directed
      behaviour problems to use "implementation intentions". This technique, which has
      been shown to improve different aspects of goal-directed behaviour enactment,
      consists of establishing a mental (verbal and/or visual) link between the action
      that must be performed and the situation in which it must be performed. Our
      programme proposes exercises of progressively increasing difficulty that are
      targeted at daily life situations. Our second objective was to test the programme
      in small groups of older adults. Preliminary data regarding the programme's
      feasibility and its initial efficacy show a significant improvement in the main
      outcome measure, a questionnaire assessing goal-directed behaviours in everyday
      life. The participants also reported being significantly less bothered by their
      difficulties, although there were no significant changes in quality of life, self
      esteem, anxiety or depression. Two participants with different psychological
      profiles, who benefited differently from the intervention, are then presented in
      more detail. 

PMID- 24559525
TI  - The effect of various interim fixed prosthodontic materials on the polymerization
      of elastomeric impression materials.
AB  - STATEMENT OF PROBLEM: After tooth preparation, interim fixed prosthodontic
      materials are used to fabricate interim restorations until the definitive
      restoration can be delivered. The polymerization of elastomeric impression
      materials may be inhibited when in indirect contact with interim fixed
      prosthodontic materials. PURPOSE: The purpose of this study was to detect whether
      the polymerization of 6 commonly used types of elastomeric impression materials
      was affected by direct contact with 6 commonly used interim fixed prosthodontic
      materials and to further evaluate the efficacy of several decontamination methods
      to eliminate the indirect effect of the interim fixed prosthodontic materials on
      the setting of elastomeric impression materials. MATERIAL AND METHODS: Six brands
      of elastomeric impression material (Virtual, Aquasil, Genie, Correct Plus,
      Express, Impregum) were evaluated in vitro after direct contact with various
      interim fixed prosthodontic materials (Trim Plus, Unifast, Integrity, Systemp
      C&B, Tuff-Temp, Protemp IV) by 3 general practitioners. The setting of the
      impression materials was visually scored as either inhibited or noninhibited.
      Latex was used as a positive control. The decontamination part of the study was
      done indirectly on the dentin of prepared natural teeth after they had been
      relined with the interim fixed prosthodontic material. The decontamination
      methods were air-water rinse, mouthwash (chlorhexidine 0.12%), 3% hydrogen
      peroxide, and pumice. A Kruskal-Wallis nonparametric analysis was used to
      evaluate the results. RESULTS: Statistically significant setting inhibition was
      found with 5 brands of polyvinyl siloxane impression materials with all tested
      types of interim fixed prosthodontic material (P<.001) except Trim Plus. No
      tested interim fixed prosthodontic material caused inhibition with the polyether
      impression material, except for minimal inhibition with Protemp IV. The
      decontamination method performed with 3% H2O2 alone proved adequate in preventing
      impression material inhibition. Interexaminer reliability data were analyzed with
      the kappa correlation analysis. The examiners were in complete agreement (kappa
      +1). CONCLUSION: Under these in vitro conditions, the direct contact of polyvinyl
      siloxane impression materials to some brands of interim fixed prosthodontic
      materials resulted in polymerization inhibition. Of the decontamination methods
      tested, only 3% H2O2 showed efficacy in preventing the inhibitory effect of the
      interim fixed prosthodontic material. For optimal results, definitive impressions
      should be made before the prepared tooth is exposed to an interim fixed
      prosthodontic material.

PMID- 24559526
TI  - Effect of surface treatment on stress distribution in immediately loaded dental
      implants--a 3D finite element analysis.
AB  - OBJECTIVE: To investigate, by means of FE analysis, the effect of surface
      roughness treatments on the distribution of stresses at the bone-implant
      interface in immediately loaded mandibular implants. MATERIALS AND METHODS: An
      accurate, high resolution, digital replica model of bone structure (cortical and
      trabecular components) supporting an implant was created using CT scan data and
      image processing software (Mimics 13.1; Materialize, Leuven, Belgium). An
      anatomically accurate 3D model of a mandibular-implant complex was created using
      a professional 3D-CAD modeller (SolidWorks, DassaultSystemes Solid Works Corp;
      2011). Finite element models were created with one of the four roughness
      treatments on the implant fixture surface. Of these, three were surface treated
      to create a uniform coating determined by the coefficient of friction (MU); these
      were either (1) plasma sprayed or porous-beaded (MU=1.0), (2) sandblasted
      (MU=0.68) or (3) polished (MU=0.4). The fourth implant had a novel two-part
      surface roughness consisting of a coronal polished component (MU=0.4) interfacing
      with the cortical bone, and a body plasma treated surface component (MU=1)
      interfacing with the trabecular bone. Finite element stress analysis was carried
      out under vertical and lateral forces. RESULTS: This investigation showed that
      the type of surface treatment on the implant fixture affects the stress at the
      bone-implant interface of an immediately loaded implant complex. Von Mises stress
      data showed that the two-part surface treatment created the better stress
      distribution at the implant-bone interface. SIGNIFICANCE: The results from this
      FE computational analysis suggest that the proposed two-part surface treatment
      for IL implants creates lower stresses than single uniform treatments at the bone
      implant interface, which might decrease peri-implant bone loss. Future
      investigations should focus on mechanical and clinical validation of these FE
      results.

PMID- 24559527
TI  - [Complications of silicone oil tamponade].
AB  - Silicone oil tamponade is used for the management of complicated retinal
      detachment. Patients should be closely monitored as many complications may occur
      with intraocular silicone oil. Short-term complications include temporarily
      increased intraocular pressure and anterior segment inflammation. Long-term
      complications include cataract, emulsification, ocular hyper- or hypotension,
      keratopathy and retinal redetachment associated with proliferative
      vitreoretinopathy. 

PMID- 24559528
TI  - [The periphery of the vitrectomised eye].
AB  - The periphery of the vitrectomised eye is the site of retinal breaks in 1 to 15%
      of cases. These breaks must be looked for and treated to avoid retinal
      detachment. They are more frequent in the presence of fragile lesions in high
      myopia, or vitreoretinal traction. They can be related to vitreous incarceration
      in a sclerotomy site or with the movements of the vitrectomy probe. Traction is
      proportional to aspiration rate, and inversely proportional to the distance
      between the cutter and the vitreous base. Twenty-three- or 25-gauge
      transconjunctival vitrectomy seems to decrease the risk of vitreous incarceration
      and peripheral retinal tear. 

PMID- 24559529
TI  - [Multifocal choroidal ischemia in preeclampsia: report of two cases].
AB  - INTRODUCTION: Multifocal choroidal ischemia is a complication of severe
      hypertension, notably in preeclampsia. It is a rare phenomenon due to multiple
      choriocapillaris occlusions. CLINICAL OBSERVATIONS: We report the cases of two
      patients, age 28 and 32 years, 34 and 26 weeks since last menstrual period,
      respectively. The first had controlled preeclampsia under treatment. The second
      had developed Hemolysis, Elevated Liver enzymes, Low Platelet count (HELLP)
      syndrome complicated by in utero fetal death. Both patients reported visual loss.
      Comprehensive ophthalmological examination and fluorescein angiography confirmed
      the diagnosis of multifocal choroidal ischemia, in the acute stage in the first
      patient and cicatricial in the second. CONCLUSION: Acute choroidal ischemia is an
      ocular vascular syndrome which must be ruled out by systematic examination in any
      preeclamptic patient, so as to make the diagnosis and begin treatment early.

PMID- 24559530
TI  - Risk reduction of serious complications from manual therapy: are we reducing the
      risk?: correspondence to: International framework for examination of the cervical
      region for potential of cervical arterial dysfunction prior to orthopaedic manual
      therapy intervention by A. Rushton et al.

PMID- 24559531
TI  - Neuropsychological deficits in young adults born small-for-gestational age (SGA)
      at term.
AB  - Reduced IQ, learning difficulties and poor school performance have been reported
      in small-for-gestational-age (SGA) subjects. However, few studies include a
      comprehensive neuropsychological assessment. Our aim was to study
      neuropsychological functioning in young adults born SGA at term. A comprehensive
      neuropsychological test battery was administered to 58 SGA subjects (birth weight
      <10th centile) born at term, and 81 term non-SGA controls (birth weight >=10th
      centile). The SGA group obtained significantly (p < .01) lower scores on the
      attention, executive and memory domains compared to non-SGA controls and showed
      higher risk of obtaining scores below -1.5 SD on the memory domain (odds ratio =
      13.3, 95% confidence interval: 1.57, 112.47). At a subtest level, the SGA group
      obtained lower scores on most neuropsychological tests, with significant
      differences on 6 of 46 measures: the Trail Making Test 3 (letter sequencing), the
      Wechsler Memory Scale mental control and the auditory immediate memory scale, the
      Design Fluency, the Stroop 3 (inhibition) and the Visual Motor Integration (VMI)
      motor coordination subtest. Young adults born SGA score more poorly on
      neuropsychological tests compared with non-SGA controls. Differences were modest,
      with more significant differences in the memory domain.

PMID- 24559532
TI  - Recent trends in internal medicine education: a brief update.
AB  - This perspective attempts to bring graduate medical offices, residency programs
      and medical students interested in categorical internal medicine (CIM) a brief
      update on the American Board of Internal Medicine (ABIM), Accreditation Council
      for Graduate Medical Education (ACGME) and the National Registry for Medical
      Programs (NRMP) changes for the past 3-5 years in the United States (US). The US
      model for certification and recertification may serve as a homogenous example for
      other countries. This model will be described so that there is an understanding
      of the importance of such changes in the American system and its effect on
      resident education. This is critical knowledge for both teachers and learners in
      internal medicine in preparation for a lifetime career and requirements for
      certification/credentialing for both programs and their residents/fellows. Data
      from the review indicate a small increase in the number of applicants but a
      concordant decrease in ABIM initial certification exams. Programs should well be
      aware of the new focus on outcomes via the Next Accreditation System (NAS) being
      put forth by the ACGME.

PMID- 24559533
TI  - Comparison of the accuracy of kriging and IDW interpolations in estimating
      groundwater arsenic concentrations in Texas.
AB  - Exposure to arsenic causes many diseases. Most Americans in rural areas use
      groundwater for drinking, which may contain arsenic above the currently allowable
      level, 10ug/L. It is cost-effective to estimate groundwater arsenic levels based
      on data from wells with known arsenic concentrations. We compared the accuracy of
      several commonly used interpolation methods in estimating arsenic concentrations
      in >8000 wells in Texas by the leave-one-out-cross-validation technique.
      Correlation coefficient between measured and estimated arsenic levels was greater
      with inverse distance weighted (IDW) than kriging Gaussian, kriging spherical or
      cokriging interpolations when analyzing data from wells in the entire Texas
      (p<0.0001). Correlation coefficient was significantly lower with cokriging than
      any other methods (p<0.006) for wells in Texas, east Texas or the Edwards
      aquifer. Correlation coefficient was significantly greater for wells in
      southwestern Texas Panhandle than in east Texas, and was higher for wells in
      Ogallala aquifer than in Edwards aquifer (p<0.0001) regardless of interpolation
      methods. In regression analysis, the best models are when well depth and/or
      elevation were entered into the model as covariates regardless of area/aquifer or
      interpolation methods, and models with IDW are better than kriging in any
      area/aquifer. In conclusion, the accuracy in estimating groundwater arsenic level
      depends on both interpolation methods and wells' geographic distributions and
      characteristics in Texas. Taking well depth and elevation into regression
      analysis as covariates significantly increases the accuracy in estimating
      groundwater arsenic level in Texas with IDW in particular. 

PMID- 24559535
TI  - Alkali metal cation interactions with 15-crown-5 in the gas phase: revisited.
AB  - Quantitative interactions of the alkali metal cations with the cyclic 15-crown-5
      polyether ligand (15C5) are studied. In this work, Rb(+)(15C5) and Cs(+)(15C5)
      complexes are formed using electrospray ionization and studied using threshold
      collision-induced dissociation with xenon in a guided ion beam tandem mass
      spectrometer. The energy-dependent cross sections thus obtained are interpreted
      to yield bond dissociation energies (BDEs) using an analysis that includes
      consideration of unimolecular decay rates, internal energy of the reactant ions,
      and multiple ion-neutral collisions. 0 K BDEs of 175.0 +/- 9.7 and 159.4 +/- 9.6
      kJ/mol, respectively, are determined and exceed those previously measured [J. Am.
      Chem. Soc. 1999, 121, 417-423] by 68 and 57 kJ/mol, respectively, consistent with
      the hypothesis proposed there that excited conformers had been studied. Because
      the analysis techniques have advanced since this early study, we also reanalyze
      the published data for the Na(+)(15C5) and K(+)(15C5) systems to ensure a self
      consistent interpretation of all four systems. Revised BDEs for these systems are
      296.1 +/- 15.5 and 215.6 +/- 10.6 kJ/mol, respectively, which are within
      experimental uncertainty of the previously reported values. In addition, quantum
      chemical calculations are conducted at the B3LYP/def2-TZVPPD level of theory with
      theoretical BDEs in reasonable agreement with experiment. Computations are also
      used to explore features of the potential energy surfaces for isomerization of
      the M(+)(15C5) complexes.

PMID- 24559534
TI  - 5-Aza-2'-deoxycytidine potentiates antitumour immune response induced by
      photodynamic therapy.
AB  - Photodynamic therapy (PDT) of tumours is based on administration of a
      photosensitiser followed by irradiation of the tumour with visible light leading
      to production of reactive oxygen species that cause direct tumour cell death and
      vascular damage. PDT also initiates acute local inflammation, which facilitates
      the development of adaptive antitumour immunity. It has recently been reported
      that PDT can induce strong antitumour immunity towards tumours cells expressing
      P1A, tumour-associated antigen. Using four different tumour models, we show that
      antitumour immune response can be further improved when PDT is combined with a
      clinically approved epigenetic agent that induces expression of a silenced P1A
      antigen. Induction of P1A with 5-aza-2'-deoxycytidine, a methyltransferase
      inhibitor, resulted in potentiated antitumour effects in mice with Lewis lung
      carcinoma and 4T1 mammary carcinoma when combined with PDT treatment. In CT26
      colon carcinoma and EMT6 mammary carcinoma models the combination therapy
      resulted in complete responses and long-term survival. All long-term surviving
      mice were resistant to re-inoculation with the same tumour cells. Antitumour
      efficacy of the combination treatment was severely impaired by depletion of
      CD8(+) cytotoxic T cells, whereas adoptive transfer of CD8(+) T cells from long
      term surviving mice allowed for significant tumour growth delay in tumour-bearing
      mice. Taken together, these findings show that PDT leads to strong specific
      antitumour immune responses, and that epigenetic modification of tumour antigens
      levels may be a novel approach to further enhance the effectiveness of PDT. The
      present results provide a strong rationale for clinical development of this
      therapeutic approach. 

PMID- 24559536
TI  - Mortality and extraintestinal cancers in patients with primary sclerosing
      cholangitis and inflammatory bowel disease.
AB  - INTRODUCTION: Primary sclerosing cholangitis (PSC) and inflammatory bowel disease
      (IBD) frequently co-occur. PSC is associated with increased risk for colorectal
      cancer (CRC). However, whether PSC is associated with increased risk of
      extraintestinal cancers or affects mortality in an IBD cohort has not been
      examined previously. METHODS: In a multi-institutional IBD cohort of IBD, we
      established a diagnosis of PSC using a novel algorithm incorporating narrative
      and codified data with high positive and negative predictive value. Our primary
      outcome was occurrence of extraintestinal and digestive tract cancers. Mortality
      was determined through monthly linkage to the social security master death index.
      RESULTS: In our cohort of 5506 patients with CD and 5522 patients with UC, a
      diagnosis of PSC was established in 224 patients (2%). Patients with IBD-PSC were
      younger and more likely to be male compared to IBD patients without PSC; three
      quarters had UC. IBD-PSC patients had significantly increased overall risk of
      cancers compared to patients without PSC (OR 4.36, 95% CI 2.99-6.37). Analysis of
      specific cancer types revealed that a statistically significant excess risk for
      digestive tract cancer (OR 10.40, 95% CI 6.86-15.76), pancreatic cancer (OR
      11.22, 95% CI 4.11-30.62), colorectal cancer (OR 5.00, 95% CI 2.80-8.95), and
      cholangiocarcinoma (OR 55.31, 95% CI 22.20-137.80) but not for other solid organ
      or hematologic malignancies. CONCLUSIONS: PSC is associated with increased risk
      of colorectal and pancreatobiliary cancer but not with excess risk of other solid
      organ cancers.

PMID- 24559537
TI  - The changing risk of Plasmodium falciparum malaria infection in Africa: 2000-10:
      a spatial and temporal analysis of transmission intensity.
AB  - BACKGROUND: Over a decade ago, the Roll Back Malaria Partnership was launched,
      and since then there has been unprecedented investment in malaria control. We
      examined the change in malaria transmission intensity during the period 2000-10
      in Africa. METHODS: We assembled a geocoded and community Plasmodium falciparum
      parasite rate standardised to the age group 2-10 years (PfPR2-10) database from
      across 49 endemic countries and territories in Africa from surveys undertaken
      since 1980. The data were used within a Bayesian space-time geostatistical
      framework to predict PfPR2-10 in 2000 and 2010 at a 1 * 1 km spatial resolution.
      Population distribution maps at the same spatial resolution were used to compute
      populations at risk by endemicity class and estimate population-adjusted PfPR2-10
      (PAPfPR2-10) for each of the 44 countries for which predictions were possible for
      each year. FINDINGS: Between 2000 and 2010, the population in hyperendemic (>50%
      to 75% PfPR2-10) or holoendemic (>75% PfPR2-10) areas decreased from 218.6
      million (34.4%) of 635.7 million to 183.5 million (22.5%) of 815.7 million across
      44 malaria-endemic countries. 280.1 million (34.3%) people lived in areas of
      mesoendemic transmission (>10% to 50% PfPR2-10) in 2010 compared with 178.6
      million (28.1%) in 2000. Population in areas of unstable or very low transmission
      (<5% PfPR2-10) increased from 131.7 million people (20.7%) in 2000 to 219.0
      million (26.8%) in 2010. An estimated 217.6 million people, or 26.7% of the 2010
      population, lived in areas where transmission had reduced by at least one PfPR2
      10 endemicity class. 40 countries showed a reduction in national mean PAPfPR2-10.
      Only ten countries contributed 87.1% of the population living in areas of
      hyperendemic or holoendemic transmission in 2010. INTERPRETATION: Substantial
      reductions in malaria transmission have been achieved in endemic countries in
      Africa over the period 2000-10. However, 57% of the population in 2010 continued
      to live in areas where transmission remains moderate to intense and global
      support to sustain and accelerate the reduction of transmission must remain a
      priority. FUNDING: Wellcome Trust.

PMID- 24559538
TI  - Malaria control in Africa: progress but still much to do.

PMID- 24559539
TI  - Spontaneous coronary artery dissection associated with beta-HCG injections and
      fibromuscular dysplasia.
AB  - Spontaneous coronary artery dissection (SCAD) is an infrequent cause of acute
      coronary syndrome predominantly affecting younger women. SCAD is often associated
      with predisposing arterial abnormalities and precipitating emotional, physical,
      and hormonal stressors. We previously showed that fibromuscular dysplasia is
      strongly associated with SCAD and may be a causative factor. Hormonal changes
      related to pregnancy and sex hormones have also been shown to be an important
      cause of SCAD. We describe the first case report, to our knowledge, of SCAD
      associated with beta-human growth hormone injections in a patient with
      concomitant FMD. 

PMID- 24559540
TI  - [Multiple bone infarcts].

PMID- 24559541
TI  - [Outbreak of lead poisoning associated with Ayurvedic medicine].
AB  - BACKGROUND AND OBJECTIVE: Lead poisoning is normally caused by repeated
      occupational inhalation of lead. However, lead may also be absorbed through the
      digestive route. Some alternative medical treatments, such as Ayurvedic medicine,
      can also contain lead and may result in poisoning. PATIENTS AND METHOD: We
      collected cases of lead poisoning related to Ayurvedic treatments attended at the
      Hospital Clinic of Barcelona. RESULTS: Two female patients, aged 45 and 57 years,
      respectively, who initiated Ayurvedic treatments which involved the ingestion of
      various medicaments, were included. The first patient presented with anemia and
      abdominal pain. The lead level was 74MUg/dL and free erythrocyte protoporphyrin
      was 163MUg/dL. She was treated with intravenous calcium disodium
      ethylenediaminetetraacetic acid (CaNa2EDTA) and later with oral
      dimercaptosuccinic acid (DMSA) with a good evolution. The second patient
      presented with abdominal pain and a Burton's line. The lead level was 52MUg/dL
      and free erythrocyte protoporphyrin was 262MUg/dL. She was treated with oral DMSA
      and evolved favorably. Lead concentrations in some of the tablets supplied to the
      patients reached 2,003 and 19,650MUg/g of tablet. CONCLUSIONS: Lead poisoning may
      result from treatments based on Ayurvedic medicine and may reach epidemic
      proportions. Health control of alternative medicines is necessary.

PMID- 24559542
TI  - [Effect of chewing gum on halitosis].
AB  - BACKGROUND AND OBJECTIVE: This study aims to estimate the prevalence of oral
      halitosis in a young population and show the effect of chewing gum on their
      breath. PATIENTS AND METHOD: Prospective, descriptive correlational cross section
      study. We selected a convenience sample of 121 young individuals and 98 completed
      the study. It was carried out at the University Dental Hospital-University of
      Barcelona. The protocol consisted of: questionnaire, oral clinical evaluation,
      organoleptic tests (OT) and measurement of volatile sulfur compounds (VSC) with
      sulphide monitoring before and after chewing gum during 15 min, with 2 calibrated
      investigators. RESULTS: A percentage of 87.8 had adequate oral hygiene, 17.3%
      reported bad breath and 29.6% had xerostomia. Forty-four subjects had a OT grade
      >=2; the agreement of examiners was 75%. The VSC in 53 individuals were <=100
      parts per billion (ppb) and in 45 subjects, it was>100 ppb. A post-reduction of
      VSC of 17.34% was obtained with a mean decrease of 1.8-9.0 ppb (P=.003).
      CONCLUSIONS: The prevalence of halitosis was 36.7%. The use of chewing gum as an
      adjunct in cases of halitosis decreases the VSC, improving the perception of
      others and the patient.

PMID- 24559543
TI  - [Utility of bone turnover markers in metabolic bone disease detection in patients
      with phenylketonuria].
AB  - BACKGROUND AND OBJECTIVE: Mineral bone disease is more common in phenylketonuric
      patients. The objectives of this study were to determine the usefulness of
      biochemical bone markers to identify phenylketonuric patients with mineral bone
      disease (MBD) and know the underlying bone remodeling alterations. PATIENTS AND
      METHOD: Cross-sectional study of 43 phenylketonuric patients>7 years (range: 7.1
      41 years). A nutritional survey was performed and bone alkaline phosphatase
      (BAP), procollagen type 1 N-terminal propeptide (PNP-1), beta-crosslaps and ratio
      calcium/creatinine in urine were determined. RESULTS: A percentage of 20.9 of
      patients had pathological biochemical bone markers, 90% of them being adults. BAP
      was decreased in 70% of them and beta-crosslaps in 42.8%. BAP values were more
      often pathological in phenylketonuric patients with a late diagnosis (41.7 vs.
      10.7%; P<.05) and in patients with MBD (60 vs. 14.3%; P<.05). PNP-1 values and
      calcium/creatinine were similar among all phenylketonuric patients regardless of
      presenting MBD, late diagnosis or tetrahydrobipterin treatment (enzyme cofactor).
      Patients with decreased BAP and beta-crosslaps had lower natural protein intake:
      BAP (0.21 +/- 0.13 vs. 0.65 +/- 0.65 g/kg; P<.05); beta-crosslaps (0.29 +/- 0.23
      vs. 0.65 +/- 0.66 g/kg; P<.05). None of the tetrahydrobiopterin treated patients
      showed altered values of BAP, PNP-1 or calcium/creatinine. CONCLUSIONS: Adult
      phenylketonuric patients with lower natural protein intake tend to have lower
      values of BAP, which is a marker that may be useful to identify patients at risk
      for MBD.

PMID- 24559544
TI  - Touch and relate: body experience among staff in habilitation services.
AB  - In habilitation centres staff meet children with different impairments, children
      who need extensive support and training while growing up. A prevailing biomedical
      view of the body in habilitation services is gradually becoming supplemented by a
      perspective on the body as constantly involved in experiencing and communicating,
      the latter involving also the bodies of the therapists. Investigating body
      experience in habilitation staff in their encounters with the children may
      provide concepts that make it easier to reflect on what is going on in the
      interaction. When shared among larger number of peers and supported by further
      research in the field, reflected body experience may become a substantial aspect
      of professional self-knowledge. Our aim with this study was to contribute to the
      understanding of what it means to be a body for other bodies in the specific
      relational context of child habilitation, and more specifically to investigate
      what role the therapists' body experience may play for professional awareness and
      practice. In the study, five physiotherapists and three special-education
      teachers spoke of physical and emotional closeness (the body as affection) but
      also of a provoking closeness (the body as provoked) with the children and of how
      their own body experience made them more attentive to the children's experience
      (the body as reference). Situations that included bodily limitations (the body as
      restriction) were described, as were situations where the body came into focus
      through the gazes of others or one's own (the body as observed). The body was
      described as a flexible tool (the body as tool), and hands were given an
      exclusive position as a body part that was constantly communicating. Three shifts
      of intentionality that form a comprehensive structure for this body experience
      were discerned. When professional reflection is evoked it may further body
      awareness, deepen reflection in practice and strengthen intercorporeality. 

PMID- 24559545
TI  - Women's experiences of their osteoporosis diagnosis at the time of diagnosis and
      6 months later: a phenomenological hermeneutic study.
AB  - This paper describes a phenomenological hermeneutic study of experiences of women
      who were recently diagnosed with osteoporosis. The research objective was to
      investigate women's experiences of living with osteoporosis during the first 6
      months after diagnosis when treatment was first prescribed. Fifteen women were
      included in the study. The inclusion criteria were a DXA scan at one of the two
      hospitals showing a T-score below -2.5 (lower back or hip), age 65 years or
      older; no previous known osteoporotic fracture; at least one of the known risk
      factors for osteoporosis; and prescription of anti-osteoporotic treatment.
      Exclusion criteria were previous diagnosis of osteoporosis or previous treatment
      with anti-osteoporotic medication. Data were collected through in-depth
      interviews shortly after diagnosis and 6 months later. The performed analyses
      were inspired by Paul Ricoeur's theory of interpretation of texts comprising
      three levels: naive reading, structural analysis, and critical interpretation and
      discussion. Three key themes emerged: 1) being diagnosed, 2) being prescribed
      medical treatment, and 3) being on the path of learning to live with
      osteoporosis. The findings suggest a need for improved support for the patients
      to gain understanding of their diagnosis and the risk of osteoporotic fracture as
      well as to learn to live with osteoporosis. The study highlights new health
      promotion areas for targeting interventions at newly diagnosed patients, helping
      them accept and interpret the diagnosis, and the medical treatment. 

PMID- 24559546
TI  - Lived experiences and challenges of older surgical patients during
      hospitalization for cancer: an ethnographic fieldwork.
AB  - This paper explores the lived experiences of older surgical patients' (aged 74
      years and older) experienced challenges during a brief admission to hospital.
      Age, gender, polypharmacy, and the severity of illness are also factors known to
      affect the hospitalization process. For an ethnographic study using participant
      observation and interviews, surgical cancer patients (n = 9, aged 74 years and
      older) were recruited during admission to a Danish teaching hospital. Using
      ethnographic strategies of participant observation and interviews, each patient
      was followed through the course of 1 day during their stay at the hospital.
      Interviews were carried out with all patients during this time. Three areas of
      concern were identified as prominent in the patients' experiences and challenges
      during their short hospital stay: teeth and oral cavity, eating in a hospital
      setting, and medication during hospitalization. Short-term hospitalization
      requires focused collaboration between staff and patient concerning individual
      challenges from their teeth and oral cavity as support of nutritional needs
      during surgical treatment for cancer. 

PMID- 24559547
TI  - Learning turning points--in life with long-term illness--visualized with the help
      of the life-world philosophy.
AB  - A long-term illness is an occurrence that changes one's life and generates a need
      to learn how to live with it. This article is based on an empirical study of
      interviews on people living with different long-term illnesses. The results have
      shown that the learning process is a complex phenomenon interwoven with life as a
      whole. The essential meaning of learning to live with long-term illness concerns
      a movement toward a change of understanding of access to the world. In this
      movement, in which everyday lives as well as relationships with oneself and
      others are affected, a continual renegotiation is needed. Texts from
      existential/lifeworld philosopher, Heidegger and Gadamer, have been used to get a
      greater understanding of the empirical results. These texts have been analysed
      with particular focus on learning turning points and the importance of
      reflection. The results are highlighted under the following themes: Pursuit of
      balance-the aim of learning, The tense grip-the resistance to learning, To live
      more really-the possibilities of the learning, Distancing-the how of the
      learning, and The tense of the learning-the whole of the learning. In those
      learning turning points are present. Knowledge from this study has been used to
      make a didactic model designed to give caregivers a tool to support patients'
      learning. The didactic model is called: The challenge to take charge of life with
      a long-term illness. 

PMID- 24559549
TI  - NICU nurses' ambivalent attitudes in skin-to-skin care practice.
AB  - This article illuminates the essence of Neonatal Intensive Care Unit (NICU)
      nurses' attitudes in skin-to-skin care (SSC) practice for preterm infants and
      their parents. Health care providers are in a unique position to influence the
      dynamic between infants and parents, and SSC affects both partners in the dyad.
      The design is descriptively phenomenological in terms of reflective lifeworld
      approach. Eighteen Swedish, Danish, and Norwegian nurses from NICUs offering
      varied possibilities and extents of SSC participated. NICU nurses' attitudes in
      SSC practice are ambivalent. The nurses consider the sensory, wellness, and
      mutuality experiences to be primary and vital and enact SSC as much as possible.
      But "as much as possible" is a broad and varied concept, and their attitudes are
      ambivalent in terms of not always facilitating what they consider to be the
      optimal caring conditions. The source of NICU nurses' ambivalent attitudes in SSC
      practice is a complex interplay of beliefs, norms, and evidence, which have a
      multidisciplinary basis. The ambivalent attitudes are, to a great extent, the
      result of the need to balance these multidisciplinary concerns. This needs to be
      acknowledged in considering SSC practice, as well as acknowledging that clinical
      judgments concerning optimal SSC depend on parents and infants unlimited access
      to each other, which NICU nurses can influence. 

PMID- 24559550
TI  - Children with disabilities--an overview of their situation.

PMID- 24559548
TI  - "Struggling for independence": the meaning of being an oldest old man in a rural
      area. Interpretation of oldest old men's narrations.
AB  - The amount of older people receiving home nursing care is increasing; in rural
      areas, they are at additional risk because of the distance between people and
      health care facilities. No specific studies have been found about oldest old men
      living alone and receiving home nursing care and the meaning of living alone in
      one's own home. The aim of this study was therefore to illuminate the meaning of
      being an oldest old man living alone in a rural area and receiving home nursing
      care. A sample of 12 oldest old men living in rural areas in the middle of Norway
      was chosen for this study. Narrative interviews were conducted, and data were
      analyzed using the phenomenological hermeneutical method. After a naive reading
      and a structural analysis of the text, we identified three themes: feelings of
      insufficiency in everyday life, finding hope in life, and feeling reconciliation
      with life. The comprehensive understanding suggested that being an oldest old man
      living alone in a rural area means a struggle between a dependent existence and a
      desire to be independent. Living in the tension between independence and
      dependency is a complex emotional situation where one is trying to accept the
      consequences of life and loss--reconciling the wish to live with the fact that
      life will come to an end.

PMID- 24559551
TI  - Update on sexually transmitted infections.

PMID- 24559552
TI  - Sexually transmitted infections in men who have sex with men.
AB  - Homosexuality is a global human phenomenon. Although the American Psychiatric
      Association removed homosexuality from its list of disorders more than 35years
      ago, homophobia among physicians is still widely prevalent. Men who have sex with
      men (MSM) form a relatively new epidemiological risk group for STI. To perform
      correct management, clinicians evaluating men with male-male sex contacts for STI
      related complaints or STI screening must obtain a thorough sexual history.
      Emerging STI like lymphogranuloma venereum, hepatitis C, and multidrug resistant
      N. gonorrhea strains have been described first in MSM. STI related proctitis
      often occur in MSM. Within the MSM population, HIV positive patients form a
      special group affected by STI related diseases, such as anal carcinoma and
      neurosyphilis. The final part of this review concludes with recommendations to
      reduce the STI burden in MSM. 

PMID- 24559553
TI  - Sexual health in adolescents.
AB  - Young people are particularly vulnerable to poor sexual health outcomes of high
      rates of sexually transmitted infections (STIs) and unwanted pregnancy. They
      partake in riskier sexual behaviors with higher rates of sexual partner change
      and poor levels of contraception, including condom use. Access to services may be
      limited either through lack of appropriate services or disinclination to seek out
      services. We review the biological, cognitive, behavioral, and socioeconomic risk
      factors that contribute to their poor sexual health outcomes. Details include the
      epidemiology, presentation and complications of STIs and pregnancy in
      adolescents, the clinical assessment of adolescents, contraception options,
      confidentiality, consent and safeguarding, and key characteristics of successful
      adolescent services. 

PMID- 24559554
TI  - Skin as an indicator for sexually transmitted infections.
AB  - Cutaneous signs and skin conditions associated with sexually transmitted
      infections (STIs) are discussed. Syphilis, condyloma acuminata, and scabies are
      well-known STIs with cutaneous manifestations. Chlamydia and gonorrhea can also
      cause specific muco-cutaneous signs and symptoms. HIV often manifests itself
      through skin conditions. Dermatologists are pivotal in the timely diagnosis of
      HIV infection and play an important role in the disease prognosis and ongoing
      transmission. Anal intra-epithelial neoplasia (AIN), an HPV related precursor of
      anal carcinoma affecting HIV positive men, is a relatively new condition that
      many dermatologists will face in the future. STIs should be involved in the
      differential diagnosis when dermatologists are confronted with anogenital
      dermatoses, especially in patients with an increased risk for STIs. 

PMID- 24559555
TI  - Changing patterns and progress in venereology.
AB  - This paper provides a summary of the philosophy of modern concepts on
      venereology, the control and treatment of sexually transmitted infections (STIs).
      There is a basis in professional education, based on evidence based medicine.
      From that follows a much wider dissemination to the public on the personal and
      community aspects of STIs. The World Wide Web has had profound effects on rapid
      developments in this field. STIs are more frequent in some groups in the general
      population. Epidemiological trends in STIs from the United States and Europe are
      described. Interventions to prevent the spread of STIs not only by changing
      personal preventive behavior but through research based on applied medical
      science, such as developments in chemotherapy and vaccines, already efficacious
      to prevent hepatitis A and B and some genital human papilloma virus infections,
      should be pursued. Venereology, as a major component of dermatovenereology, not
      only encompasses all of pathology, internal medicine, and therapeutics, but also,
      most importantly, sexual behavior and its consequences as part of humanity. It
      also has a major role in community medicine and public health, where the world of
      medicine meets politics and the media. Sexually transmitted infections have
      always affected human beings. If STIs are not prevented, not only are there the
      immediate consequences requiring medical intervention, but also long term results
      of chronic morbidity, such as infertility in women and congenital syphilis, and
      in some instances, such as syphilis, viral hepatitis, genital human papilloma
      virus infection and its neoplastic sequaelae, and HIV/AIDS, an early death. 

PMID- 24559556
TI  - Syphilis in the United States.
AB  - Syphilis gained notoriety in the 1500s, when it became widespread throughout
      Europe. While the origins of syphilis are not certain, recent data have shown
      that it may have originated in the Americas from a close relative that causes
      Yaws (Treponema pallidum pertenue).(1) For the past 500years, the disease has
      shown its various faces all over the world. The 19th century saw an entire
      medical subspecialty-syphilology (sometimes known as syphilography)-devoted to
      the study of the great disease, then known as "the great imitator." Syphilis has
      an entire textbook of presentations and can mimic many other infections and
      immune-mediated processes. At the beginning of the 20th century, the many faces
      of the disease led to Sir William Osler's well-known aphorism, "The physician who
      knows syphilis knows medicine."(2) When penicillin was discovered, and used to
      treat syphilis in 1943, some thought that syphilis would go by the wayside, but
      syphilis continued what it has been doing for so many years . . . inconspicuously
      infecting humans. The United States has seen the incidence of syphilis increase
      numerous times throughout the past 70years. Every decrease in the incidence of
      syphilis is followed shortly by an increase. A marked shift in the epidemiology
      occurred from 1990 to 2000. In the 1990s, syphilis primarily occurred in
      heterosexual minority groups. In the new millennium, a majority of cases of
      syphilis are now transmitted among men who have sex with men (MSM).(3) This
      contribution discusses the incidence of syphilis in the United States and the
      reasons these trends continue. 

PMID- 24559557
TI  - Endemic syphilis in Europe.
AB  - Nonvenereal syphilis (endemic syphilis) has existed in Europe since the 16th
      century. Main characteristics of the disease are its presence for a longer time
      in a specific territory and its transmission regardless of age and sex, mainly
      extragenitally in unsanitary living conditions. Nonvenereal syphilis was
      described under different names in almost all regions of Europe. The primary
      genital chancre was absent, and lesions were most frequently found in the mouth
      and affected mostly children. The disease spread in rural areas with poor
      economic and hygienic conditions. The disease was eradicated in Europe in the
      20th century, but it is still present in some rural regions of the Arabian
      Peninsula, Southwest Asia, and North Africa. 

PMID- 24559558
TI  - HPV-associated diseases.
AB  - Nearly 200 distinct human papilloma viruses (HPVs) have now been recognized, and
      each is associated with a specific set of clinical lesions. They are associated
      with a spectrum of diseases, from benign verrucae vulgares and condylomata
      acuminata to the malignancies of the cervix, vulva, anus, and penis. Disease
      associated with HPV can be divided into skin and mucosal lesion of the genital
      and extragenital regions. The relationship between HPV and nonmelanoma skin
      cancer (NMSC) is important clinically, because NMSC is the most common form of
      malignancy among fair-skinned populations. HPVs have also been detected in skin
      tags, lichen sclerosus, seborrheic keratoses, actinic keratoses, epidermal cysts,
      psoriatic plaques, and plucked hairs, but cutaneous HPV can be found on healthy
      skin. 

PMID- 24559559
TI  - Prophylactic papillomavirus vaccines.
AB  - Human papillomaviruses (HPV) are the causative agents of cervical cancer, the
      third most common cancer in women. The development of prophylactic HPV vaccines
      Gardasil(r) and Cervarix(r) targeting the major oncogenic HPV types is now the
      frontline of cervical cancer prevention. Both vaccines have been proven to be
      highly effective and safe although there are still open questions about their
      target population, cross-protection, and long-term efficacy. The main limitation
      for a worldwide implementation of Gardasil(r) and Cervarix(r) is their high cost.
      To develop more affordable vaccines research groups are concentrated in new
      formulations with different antigens including capsomeres, the minor capsid
      protein L2 and DNA. In this article we describe the vaccines' impact on HPV
      associated disease, the main open questions about the marketed vaccines, and
      current efforts for the development of second-generation vaccines. 

PMID- 24559560
TI  - Human papillomavirus status in extragenital nonmelanoma skin cancers.
AB  - About 5% of all cancers worldwide can be attributed to human papillomaviruses
      (HPVs); namely, six sites are strongly associated with HPV infections: cervix,
      penis, vulva, vagina, anus, and oropharynx. Nonmelanoma skin cancers (NMSC),
      basal cell carcinoma (BCC), and squamous cell carcinoma (SCC) are the most common
      malignancies in Caucasians. In fact, there is an intense connection between
      sunlight exposure, fair skin, HPV, and development of NMSC. We have conducted a
      pilot study that included tissue samples from 26 carcinoma patients, of which
      there were 13 BCC and 13 SCC. HPV detection and typing was done with DNA
      amplification and sequencing, respectively. In total, 23.1% of SCC samples (3/13)
      and 7.7% of BCC samples (1/13) were positive for HPV DNA. The importance of
      understanding all aspects of NMSC carcinogenesis may be to reveal novel
      therapeutic options or preventive measures for HPV containing NMSC patients. 

PMID- 24559561
TI  - Human papillomavirus-associated diseases.
AB  - The human papillomavirus (HPV) may be associated with various oral, genital, and
      cutaneous conditions, both benign and malignant. The association between sexually
      transmitted alpha-HPV types is the strongest with cervical cancer because almost
      all such malignancies contain viral DNA, notably HPV types 16 and 18. The
      contribution of cancer causing HPV types in other anogenital, oral, and
      oropharyngeal malignancies, plus benign disorders, is lower and with a less
      significant public health concern. Cervical cytologic screening is a well
      established preventive measure that allows early detection and successful
      treatment of precancerous cervical lesions. In cases of all other HPV-associated
      disorders, early detection of a precancerous lesion is either difficult or almost
      impossible. HPV vaccination remains the only preventive measure against most HPV
      related diseases. 

PMID- 24559562
TI  - Nonspecific genital ulcers.
AB  - Recent intervention of nonspecific genital ulcers has added refreshing dimensions
      to genital ulcer disease. It was considered pertinent to dwell on diverse
      clinical presentation and diagnostic strategies. It seems to possess spectrum. It
      includes infective causes, Epstein Bar Virus, tuberculosis, Leishmaniasis,
      HIV/AIDS related ulcers and amoebiasis. Noninfective causes are immunobullous
      disorders, aphthosis, Behcet's disease (BD), inflammatory bowel disease, lichen
      planus and lichen sclerosis et atrophicus, drug reactions, premalignant and
      malignant conditions, pyoderma gangrenosum, and hidradenitis suppurativa. The
      diagnostic features and treatment option of each disorder are succinctly outlined
      for ready reference. 

PMID- 24559563
TI  - Gonorrhea: new challenges.
AB  - As "a paradigm of the classical Venereology" for many decades, gonorrhea appears
      to be the second most common sexually transmitted infection of bacterial origin
      today. In spite of its mostly uncomplicated clinical course, gonorrhea may
      sometimes result with serious complications such as pelvic inflammatory disease,
      ectopic pregnancy, infertility, epididymitis, gonococcemia, and disseminated
      gonococcal infection. Perhaps the most important challenge today is the emergence
      of multidrug-resistant gonorrhea, which is currently the main reason for public
      concern. Eventually, Neisseria gonorrhoeae turned out to be one of the most
      "evolutionarily successful" pathogens. Effective treatment of gonorrhea providing
      that N gonorrhoeae might also facilitate the transmission of HIV is a complex
      task and almost an imperative in the "sexually transmitted infection world"
      today. 

PMID- 24559564
TI  - HIV in Europe.
AB  - In 2011, the estimated number of people living with HIV in Europe and Central
      Asia was 2.3 million. This is more than twice the 2001 figure. At the same time,
      approximately 50% of the infected people may not know their HIV status. The
      Europe/Central Asia region is one of only two regions in which HIV infections
      continue to increase. The estimated prevalence rate in the west and center of the
      region, however, has remained stable at 0.2%. The HIV epidemics in Eastern Europe
      and Central Asia are typically driven by unsafe drug injection and by onward
      transmission to the sexual partners of people who inject drugs. In the western
      part of the region, the epidemic remains concentrated among men who have sex with
      men and migrants from countries with generalized epidemics. Means of preventing
      and fighting HIV should, first and foremost, be directed to those parts of the
      population that are most exposed to the risk of the infection. Proceeding from
      the data presented, recommendations are given for ways of decreasing HIV
      prevalence in the region, such as promoting dialogue and awareness among
      multistakeholders, including policy makers, donors, and population groups most
      exposed to the infection. 

PMID- 24559565
TI  - The dermatologist and the HIV/AIDS pandemic.
AB  - The clinical course of HIV disease has changed dramatically over the last 30
      years due to insights into the disease pathogenesis, provided by basic biomedical
      research, and due to the boost of antiretroviral drugs that are able to break the
      vicious circle of viral propagation and damage to the immune system.
      Dermatologists were pivotal in the identification of the then new disease in the
      early 1980s, and continue to play an important role in identifying sentinel skin
      and mucous membrane conditions associated with HIV-1 disease, diagnosing and
      treating side effects of antiretroviral drug therapies, and helping to curb the
      spread of HIV by control of other sexually transmitted infections. 

PMID- 24559566
TI  - Chancroid, lymphogranuloma venereum, granuloma inguinale, genital herpes simplex
      infection, and molluscum contagiosum.
AB  - Chancroid, lymphogranuloma venereum, and granuloma inguinale may be considered as
      tropical venereal diseases. These diseases were a major diagnostic and
      therapeutic challenge in past centuries. Currently, patients with these bacterial
      infections that are endemic to the tropics occasionally consult with
      dermatologists in temperate climates. Due to the increasing frequency of travel
      to the tropics for tourism and work, as well as the increasing number of
      immigrants from these areas, it is important for dermatologists practicing in
      temperate climates to be familiar with the dermatologic manifestations of such
      infections, to be prepared to diagnose these diseases, and to treat these
      patients. All three "tropical" infections respond well to prompt and appropriate
      antimicrobial treatment, although herpes progenitalis still cannot be cured, and
      the number of people infected keeps growing; moreover, genital herpes can be
      transmitted by viral shedding before and after the visual signs or symptoms.
      Acyclovir, valacyclovir, and famciclovir can shorten outbreaks and make them less
      severe or even stop them from happening. There is currently no etiologic
      treatment for molluscum contagiosum, and the majority of treatment options are
      mechanical, causing a certain degree of discomfort. The molluscum contagiosum
      virus, unlike the other infectious agents mentioned, does not invade the skin. 

PMID- 24559567
TI  - Genital warts and other HPV infections: established and novel therapies.
AB  - Wart therapies involve methods of targeted lesion destruction, as well as
      selective immunologic modification. While there are several therapeutic options,
      no treatment has been proven to be superior in terms of clinical clearance or
      recurrence. Controlled trials comparing treatments are currently lacking. Many
      factors are used in the selection of treatment. Variables that should be taken
      into account include but are not limited to the morphology of the lesions such as
      thickness and size, quantity, anatomic location, human papilloma virus (HPV)
      classification, immunocompromized or immune competent status, as well as the
      preferences of the patient and the provider, cost and availability. No current
      treatment completely eradicates the human papillomavirus virus. The availability
      of vaccinations against HPV infection is contributing to the decreasing incidence
      of this disease. This contribution highlights conventional therapies, off-label
      treatment strategies including combination therapies, and prophylaxis for
      condylomata acuminata. 

PMID- 24559568
TI  - Non-infectious inflammatory genital lesions.
AB  - The genitalia may be the site of non-infectious inflammatory lesions that are
      generally manifested as balanoposthitis and vulvovaginitis. In men, these forms
      constitute 50% of all balanoposthitis forms, and in women, vulvovaginitis
      frequency is even higher. They consist of genital locations of general skin
      diseases, such as psoriasis, lichen planus, lichen sclerosus, and other clinical
      entities with their own physiognomy, such as Zoon's balanitis-vulvitis. Diagnosis
      of genital non-infectious inflammatory lesions is usually made on clinical
      criteria. A biopsy is only necessary for the identification of clinical
      conditions that may simulate inflammatory form but are actually premalignant
      processes. 

PMID- 24559569
TI  - Significance of dermatoscopy in genital dermatoses.
AB  - Dermatoscopy as a non-invasive technique has become an integrative part in the
      evaluation of pigmented and non-pigmented skin lesions, particularly for the
      early detections of melanoma. Although dermatoscopy improves diagnosis of
      pigmented and nonpigmented lesions of the skin, it is unknown if dermatoscopy
      improves the diagnostic accuracy of pigmented mucosal lesions. The
      "entodermatoscopy" is used for the dermatoscopy of skin infections and
      infestations and revised as entomodermatoscopy, as it connects the research
      fields of dermatology and entomology, with its roots being found in these two
      words. In genital dermatology along with the clinical examination, dermatoscopy
      is also used for the diagnosis and treatment follow-up of pediculosis pubis,
      genital warts, molluscum contagiosum, and scabies. 

PMID- 24559570
TI  - The path to modernity: a personal testimony to the restructuring of the
      Department of Dermatology, Vargas Hospital, Caracas, Venezuela.
AB  - In the late 1950s and early1960s, there was a concerted effort to modernize
      teaching, training, and patient care in the Vargas Hospital of Caracas,
      Venezuela. The above included the development of research in the frame of
      postgraduate training. This effort was to be helped by USA funds and institutions
      but could only be achieved by the work of Venezuelans, sharing a vision of
      progress. Dermatology spearheaded this initiative, and the fruit of this was the
      exponential development of Venezuelan Dermatology and the creation of the
      National Institute of Dermatology on the grounds of the Vargas Hospital. The
      purpose of this contribution is to review these events that happened more than
      half a century ago from my own perspective. I sincerely hope that these lines
      could serve as an inspiration to the younger generations that toil today under
      less-than-favorable conditions. 

PMID- 24559571
TI  - Clinical and histologic characteristics of clinically unsuspected melanomas.
AB  - Thin melanomas are recognized and captured by clinicians at an alarming rate,
      whereas thick melanomas remain underrecognized. Improved recognition of thick
      melanomas will require further understanding of their clinical and histologic
      characteristics at various stages of development because emerging data suggest
      that the thin melanomas being captured today may not represent the forerunners of
      the thick melanomas. In this retrospective analysis, pathology requisition forms
      from melanomas diagnosed by histopathology were examined for submitted clinical
      diagnosis, patient characteristics, melanoma thickness, and biopsy method. Three
      hundred eighty-five melanomas were identified from 2003 to 2011. Most lesions
      (71.7%) were clinically suspected to be melanocytic. The mean depth in this group
      was 0.62mm. Of the unsuspected cases (28.3%), the most common submitted diagnoses
      were basal cell carcinomas and seborrheic keratoses, consistent with previous
      reports. The mean depth in the unsuspected group was 1.64mm, and more frequently
      extended to the deep margin (51.8% vs 25.4% of the time). Shave biopsy was the
      overwhelming preferred method of biopsy (79.5% overall). Compared with thin
      melanomas, thick melanomas are underrecognized by physicians due to their lack of
      characteristic morphologic features; consequently, they are more frequently
      associated with suboptimal biopsies. 

PMID- 24559573
TI  - Expression of TGF-beta1 in Wilms' tumor was associated with invasiveness and
      disease progression.
AB  - OBJECTIVE: To detect the expression of TGF-beta1 in Wilms' tumor and association
      with disease progression. METHODS: Immunohistochemistry was used to examine TGF
      beta1 expression in 51 primary tumors and 17 invasions/metastases. Transient
      transfection was performed to establish Wilms' tumor cells with high TGF-beta1
      expression (TGF-beta1-WT), and the expression level of TGF-beta1 was detected by
      Western blot analysis. Invasive capacity of the transfected cells was evaluated
      by transwell analysis. RESULTS: The positive expression rate of TGF-beta1 was
      50.98% (26/51) and 82.35% (14/17) in primary WT tissues and associated
      invasive/metastatic tissues, respectively. The higher level of TGF-beta1
      expression in primary WT tumors was relative to invasion/metastasis (p = 0.048).
      The expression of TGF-beta1 between primary WT and matched invasive/metastatic
      tissues was concordant (p = 0.219). TGF-beta1-WT cells showed more invasive
      capacity than GFP-WT and WT cells. TGF-beta1 expression status was associated
      with disease-free survival (DFS) (50.2 months vs. 75.4 months, p = 0.022) but not
      overall survival (OS) (62.3 months vs. 75.8 months, p = 0.141). CONCLUSIONS:
      Positive expression of TGF-beta1 in WT was correlated with tumor invasion and
      disease progression, which might be useful in identifying patients at high risk
      of unfavorable outcomes.

PMID- 24559574
TI  - Duration of red blood cells storage and outcome in critically ill patients.
AB  - PURPOSE: There is conflicting evidence on the effect of red blood cells (RBC)
      storage duration and clinical outcomes. We aimed to investigate the association
      between RBC storage duration and clinical outcomes in patients admitted to the
      intensive care unit (ICU). MATERIALS AND METHODS: We retrospectively (2001-2011)
      studied adults admitted to the ICUs of 2 hospitals who received RBC. Using the
      mean, maximum and minimum age of RBC units transfused, we evaluated the
      association between RBC storage duration and mortality. We also analyzed the
      association between mean age of RBC units and length of stay (LOS) in survivors.
      We performed sensitivity analyses in patients who only received RBC in ICU and
      who only received leukodepleted RBC. RESULTS: We studied 8416 patients who
      received a median of 4 (interquartile range, 2-7) RBC units. After multivariate
      analysis, age of RBC was not independently associated with mortality, including
      in the subgroup analyses. Furthermore, there was no clinically relevant
      relationship between mean RBC age and LOS. CONCLUSIONS: RBC storage duration was
      not associated with increased mortality nor ICU and hospital LOS. These results
      support the view that the effect of RBC storage duration on outcomes in
      critically ill patients is uncertain.

PMID- 24559575
TI  - The feasibility of measuring frailty to predict disability and mortality in older
      medical intensive care unit survivors.
AB  - PURPOSE: To determine whether frailty can be measured within 4 days prior to
      hospital discharge in older intensive care unit (ICU) survivors of respiratory
      failure and whether it is associated with post-discharge disability and
      mortality. MATERIALS AND METHODS: We performed a single-center prospective cohort
      study of 22 medical ICU survivors age 65 years or older who had received
      noninvasive or invasive mechanical ventilation for at least 24 hours. Frailty was
      defined as a score of >=3 using Fried's 5-point scale. We measured disability
      with the Katz Activities of Daily Living. We estimated unadjusted associations
      between Fried's frailty score and incident disability at 1-month and 6-month
      mortality using Cox proportional hazard models. RESULTS: The mean (SD) age was 77
      (9) years, mean Acute Physiology and Chronic Health Evaluation II score was 27
      (9.7), mean frailty score was 3.4 (1.3), and 18 (82%) were frail. Nine subjects
      (41%) died within 6 months, and all were frail. Each 1-point increase in frailty
      score was associated with a 90% increased rate of incident disability at 1-month
      (rate ratio: 1.9, 95% CI 0.7-4.9) and a threefold increase in 6-month mortality
      (rate ratio: 3.0, 95% CI 1.4-6.3). CONCLUSIONS: Frailty can be measured in older
      ICU survivors near hospital discharge and is associated with 6-month mortality in
      unadjusted analysis. Larger studies to determine if frailty independently
      predicts outcomes are warranted.

PMID- 24559576
TI  - The DISPARITY Study: do gender differences exist in Surviving Sepsis Campaign
      resuscitation bundle completion, completion of individual bundle elements, or
      sepsis mortality?
AB  - PURPOSE: Women in the emergency department are less likely to receive early goal
      directed therapy, but gender differences in the Surviving Sepsis Campaign (SSC)
      bundle completion have not been studied [1]. We hypothesized that women have
      lower SSC resuscitation bundle completion rates. MATERIALS AND METHODS: This was
      a retrospective, observational study in a large urban academic ED at a national
      SSC site. Consecutive patients (age>18 years) admitted to intensive care with
      severe sepsis or septic shock and entered into the SSC database from October 2005
      to February 2012 were included. Data on overall and individual bundle elements
      were exported from the database. Bivariate analyses were performed with chi
      square tests and t-tests. Multiple logistic regression was then performed with
      gender as an effect modifier. RESULTS: Eight hundred fourteen patients were
      enrolled. The mean age was 66 years;, 44.8% were women. There was no association
      between gender and bundle completion (aOR 0.83, 95% CI 0.58-1.16), controlling
      for age, race, Sequential Organ Failure Assessment, congestive heart failure, and
      coagulopathy. In-hospital mortality did not differ by gender. Women were less
      likely to receive antibiotics within 3 hours (60.5% vs. 68.8%, p=0.01) and less
      likely to reach a target ScvO2>70 (31.3% vs. 39.5%, P=.05). CONCLUSIONS: There
      were no gender disparities in bundle completion or in-hospital mortality. Further
      research is needed to examine individual bundle elements and gender specific
      factors that may affect bundle completion and mortality.

PMID- 24559577
TI  - Prognosis of emergency department patients with suspected infection and
      intermediate lactate levels: a systematic review.
AB  - PURPOSE: Previous studies have shown a correlation between blood lactate greater
      than 4.0 mmol/L and mortality in patients with suspected infection in the
      emergency department (ED), but data are more limited regarding the prognosis of
      intermediate blood lactate (2.0-3.9 mmol/L), particularly in the absence of
      hemodynamic instability. We sought to quantify the prognostic significance of
      intermediate blood lactate levels in ED patients with suspected infection,
      emphasizing patients without hypotension. METHODS: A systematic review of 4
      databases was conducted to identify studies using a comprehensive search
      strategy. All studies performed on adult ED patients with suspected infection and
      available data on hemodynamics, intermediate lactate levels, and mortality rates
      were included. RESULTS: We identified 20 potential publications, 8 of which were
      included. Intermediate lactate elevation was found in 11,062 patients with
      suspected or confirmed infection, 1672 (15.1%) of whom died. Subgroup analysis of
      normotensive patients demonstrated a mortality of 1561 (14.9%) of 10,442, with
      rates from individual studies between 3.2% and 16.4%. CONCLUSION: This systematic
      review found that among ED patients with suspected infection, intermediate
      lactate elevation is associated with a moderate to high risk of mortality, even
      among patients without hypotension. Physicians should consider close monitoring
      and aggressive treatment for such patients.

PMID- 24559578
TI  - Contamination of liquid soap for hospital use with Raoultella planticola.
AB  - This article reports the contamination of a batch of liquid soap for hospital use
      with Raoultella planticola. The micro-organism was first identified as Klebsiella
      pneumoniae due to the inability of automated systems to characterize this
      species. There is a need to strengthen the inspection of cosmetic products to be
      used in the hospital setting. It is recommended that hospitalized patients at the
      highest risk of infection should use antimicrobial soaps for personal hygiene.
      The incidence of infections due to R. planticola is unknown as it is usually
      misclassified as Klebsiella spp. by automated systems. 

PMID- 24559579
TI  - Radio-histological correlations in breast imaging: understanding for providing
      better care.

PMID- 24559580
TI  - A need for scalable outpatient palliative care interventions.

PMID- 24559581
TI  - Early palliative care for patients with advanced cancer: a cluster-randomised
      controlled trial.
AB  - BACKGROUND: Patients with advanced cancer have reduced quality of life, which
      tends to worsen towards the end of life. We assessed the effect of early
      palliative care in patients with advanced cancer on several aspects of quality of
      life. METHODS: The study took place at the Princess Margaret Cancer Centre
      (Toronto, ON, Canada), between Dec 1, 2006, and Feb 28, 2011. 24 medical oncology
      clinics were cluster randomised (in a 1:1 ratio, using a computer-generated
      sequence, stratified by clinic size and tumour site [four lung, eight
      gastrointestinal, four genitourinary, six breast, two gynaecological]), to
      consultation and follow-up (at least monthly) by a palliative care team or to
      standard cancer care. Complete masking of interventions was not possible;
      however, patients provided written informed consent to participate in their own
      study group, without being informed of the existence of another group. Eligible
      patients had advanced cancer, European Cooperative Oncology Group performance
      status of 0-2, and a clinical prognosis of 6-24 months. Quality of life
      (Functional Assessment of Chronic Illness Therapy--Spiritual Well-Being [FACIT
      Sp] scale and Quality of Life at the End of Life [QUAL-E] scale), symptom
      severity (Edmonton Symptom Assessment System [ESAS]), satisfaction with care
      (FAMCARE-P16), and problems with medical interactions (Cancer Rehabilitation
      Evaluation System Medical Interaction Subscale [CARES-MIS]) were measured at
      baseline and monthly for 4 months. The primary outcome was change score for FACIT
      Sp at 3 months. Secondary endpoints included change score for FACIT-Sp at 4
      months and change scores for other scales at 3 and 4 months. This trial is
      registered with ClinicalTrials.gov, number NCT01248624. FINDINGS: 461 patients
      completed baseline measures (228 intervention, 233 control); 393 completed at
      least one follow-up assessment. At 3-months, there was a non-significant
      difference in change score for FACIT-Sp between intervention and control groups
      (3.56 points [95% CI -0.27 to 7.40], p=0.07), a significant difference in QUAL-E
      (2.25 [0.01 to 4.49], p=0.05) and FAMCARE-P16 (3.79 [1.74 to 5.85], p=0.0003),
      and no difference in ESAS (-1.70 [-5.26 to 1.87], p=0.33) or CARES-MIS (-0.66 [
      2.25 to 0.94], p=0.40). At 4 months, there were significant differences in change
      scores for all outcomes except CARES-MIS. All differences favoured the
      intervention group. INTERPRETATION: Although the difference in quality of life
      was non-significant at the primary endpoint, this trial shows promising findings
      that support early palliative care for patients with advanced cancer. FUNDING:
      Canadian Cancer Society, Ontario Ministry of Health and Long Term Care.

PMID- 24559583
TI  - Utilization of optical polarization microscopy in the study of sorption
      characteristics of wound dressing host materials.
AB  - Polarization microscopy was used for evaluation of kinetics of diclofenac
      sorption in three different wound dressing materials. The sorption kinetics can
      be evaluated by radii change and intensity of the light traveling through the
      fiber. The most frequently used host materials for drugs in wound dressings are
      alginate, polyesters such as polyethylene terephthalate, and viscose. We studied
      sorption of diclofenac as an example drug. Effective, but rather simple in vitro
      simulation of diclofenac sorption gives insight into the applicability of the
      mentioned materials for development of wound healing materials. 

PMID- 24559582
TI  - Cotreatment with the alpha-glucosidase inhibitor miglitol and DPP-4 inhibitor
      sitagliptin improves glycemic control and reduces the expressions of CVD risk
      factors in type 2 diabetic Japanese patients.
AB  - OBJECTIVE: In this study, we examined whether inhibition of postprandial
      hyperglycemia by combination therapy with two drugs for reducing postprandial
      hyperglycemia, i.e., alpha-glucosidase inhibitor miglitol and dipeptidyl
      peptidase (DPP)-4 inhibitor sitagliptin, improves glycemic control and reduces
      the risk of cardiovascular disease (CVD) development. MATERIALS/METHODS: We
      enrolled 32 type 2 diabetic Japanese patients with hemoglobin A1c (HbA1c) levels
      ranging from 6.9% to 10.5%, who had been treated for at least 2 months with 50mg
      miglitol (t.i.d.) or 50 mg sitagliptin (q.d.). Following a monotherapy period
      with either miglitol (Group-M) or sitagliptin (Group-S) for 1 month, the patients
      were subjected to combination therapy with sitagliptin and miglitol for 3 months.
      Meal tolerance tests were performed at the end of the monotherapy and combination
      therapy. RESULTS: Combination therapy for 3 months after monotherapy reduced
      HbA1c (changes: Group-M: -1.3%+/-0.7%, P<0.001; Group-S: -0.6%+/-0.5%, P<0.001)
      and glycoalbumin levels and increased 1,5-anhydroglucitol concentrations in the
      blood. In the meal tolerance tests, circulating active glucagon-like peptide-1
      levels were elevated in both groups, while active glucose-dependent
      insulinotropic polypeptide levels were reduced by combination therapy in the
      group with add-on miglitol therapy. The plasma protein concentrations of
      interleukin (IL)-8 and adhesion molecules (sE-selectin and sVCAM-1) were reduced
      by switching to the combination therapy, in particular with the add-on miglitol
      therapy. CONCLUSIONS: Our results suggest that combination therapy with miglitol
      and sitagliptin improves glycemic control and reduces the circulating protein
      concentrations of IL-8, sE-selectin, and sVCAM-1 in type 2 diabetic Japanese
      patients.

PMID- 24559584
TI  - Cyclooxygenase-2 and vascular endothelial growth factor expressions are involved
      in ultrafiltration failure.
AB  - BACKGROUND: Long-term peritoneal dialysis (PD) is associated with ultrafiltration
      failure (UFF). The aim of the study was to investigate changes in cyclooxygenase
      2 (COX-2), vascular endothelial growth factor A (VEGF-A), and vascular
      endothelial growth factor C (VEGF-C) expressions in a rat model of UFF induced by
      PD solution. METHODS: Sprague-Dawley rats were divided into six groups (n =
      8/group): normal untreated control group, sham operation group, uremic group
      (nephrectomy without PD), uremic 2-wk PD group (PD solution for 2 wk), uremic 4
      wk PD group (PD solution for 4 wk), and uremic 4-wk PD + celecoxib group (PD
      solution plus COX-2 inhibitor celecoxib 20 mg/kg for 4 wk). Peritoneal function
      was determined by peritoneal equilibration test. Peritoneal morphology was
      determined by hematoxylin and eosin and Masson staining. Microvessel and
      lymphatic microvessel formation was determined by immunohistochemistry. COX-2,
      VEGF-A, and VEGF-C expressions were determined by real-time polymerase chain
      reaction and immunohistochemistry. RESULTS: Uremic rat model was successfully
      established. PD-induced peritoneal morphologic changes associated with UFF,
      characterized by inflammation, edema, and collagen accumulation. PD solution
      increased the density of microvessels marked by CD31 (microvessel density) and
      lymphatic microvessels marked by LYVE-1 (lymphatic vessel density) in peritoneum.
      COX-2, VEGF-A, and VEGF-C expression levels in the uremic 4-wk PD group were
      higher than those in the uremic group (all P < 0.05). All these changes were
      partially reversed by celecoxib. VEGF-A and VEGF-C protein expressions were
      positively correlated with microvessel density and lymphatic vessel density
      formation. CONCLUSIONS: COX-2 could increase VEGF-A and VEGF-C expressions in
      peritoneal tissue, resulting in increased formation of peritoneal microvessels
      and lymphatic microvessels, playing pivotal roles in the development of UFF.

PMID- 24559585
TI  - Coupled cultivation and pre-harvesting of microalgae in a membrane
      photobioreactor (MPBR).
AB  - A new and effective concept is proposed for microalgae cultivation and pre
      harvesting using a membrane photobioreactor (MPBR), in which the bioreactor is
      coupled to membrane filtration by cultivating Chlorella vulgaris. A basic
      simulation was first performed to understand the behavior of the hybrid system.
      The effectiveness of the MPBR for cultivation and pre-harvesting was proven. The
      membrane completely retained the biomass, which then was partly recycled into the
      bioreactor to maintain a high biomass concentration, thus enhancing flexibility
      and robustness of the system. The MPBR can operate at both higher dilution and
      higher growth rates, resulting in a 9* higher biomass productivity. In addition,
      pre-harvesting can be achieved by applying variable concentration factors in the
      filtration stage. The membrane permeate was recycled to the reactor as feed
      medium without affecting the algae growth, which offers a substantial reduction
      of 77% in the water footprint. 

PMID- 24559587
TI  - The predictive value of urinary UPIb mRNA levels in VUR and recurrent urinary
      tract infections.
AB  - BACKGROUND: Vesicoureteral reflux (VUR) is a risk factor for progressive kidney
      damage especially when it is accompanied by urinary tract infections (UTIs).
      Uroplakins (UPs) are integral proteins found in the structure of urothelium. In
      the present study, we evaluated the usefulness of urinary UPIb messenger
      ribonucleic acid (mRNA) levels as an early and noninvasive diagnostic tool for
      VUR and as an indicator for predisposition to UTI. METHODS: Urinary UPIb mRNA
      levels were determined in patients experiencing their first UTI episode (n = 28)
      or recurrent UTI (n = 31) as well as patients having UTI with VUR (n = 30). These
      results were compared to a control group (n = 26). RESULTS: The UPIb mRNA values
      among patients diagnosed with their first UTI were lower, but not statistically
      different, than those in the control group. The UPIb mRNA levels of patients with
      recurrent UTI and UTI with VUR were significantly lower than those observed in
      control individuals. CONCLUSION: Urine UPIb levels may be useful for predicting
      the risk of recurrent UTI in patients diagnosed with their first UTI and may also
      be considered as a noninvasive screening test for VUR.

PMID- 24559588
TI  - Chronic kidney disease and the aging population.

PMID- 24559591
TI  - Spectroscopic separation of the methyl internal-rotational isomers of thioanisole
      isotopomers (C6H5S-CH2D and C6H5S-CHD2).
AB  - Two distinct rotational isomers of thioanisole-d1 (C6H5S-CH2D) and thioanisole-d2
      (C6H5S-CHD2) with respect to the internal rotation of the methyl moiety have been
      identified and characterized spectroscopically using the resonantly enhanced two
      photon ionization, UV-UV hole burning, and slow-electron velocity map imaging
      techniques. From the statistical weights, the definite assignment for the
      specific rotational isomer of each isotopomer has been successfully done,
      providing isomer-specific ionization energies and vibrational frequencies of
      S1/D0 states. Detailed molecular structures, the methyl internal-rotor barrier,
      and normal-mode descriptions for selective vibrations are discussed with the aid
      of density functional theory calculations. 

PMID- 24559592
TI  - Laparoscopic common bile duct exploration. Lessons learned after 200 cases.
AB  - INTRODUCTION: Laparoscopic common bile duct exploration (LCBDE) is a reliable,
      reproducible and cost-effective treatment for common bile duct stones. Several
      techniques have been described for choledochotomy closure. AIMS: To present our
      experience and the lessons learned in more than 200 cases of LCBDE. PATIENTS AND
      METHODS: Between January 1999 and July 2012, 206 patients with common bile duct
      stones underwent LCBDE. At the beginning of the series, we performed the closure
      of the CBD over a T-tube (36 patients), subsequently we favoured closure over an
      antegrade stent (133 patients) but due to a high incidence of acute pancreatitis
      in the last 16 patients we have performed primary closure. RESULTS: The 3 closure
      groups were matched for age and sex. Jaundice was the most frequent presentation.
      A total of 185 (88,5%) patients underwent choledochotomy whereas in 17 (8,7%)
      patients the transcystic route was used. The group that underwent choledochotomy
      had a larger size of stones compared to the transcystic group (9,7 vs 7,6mm). In
      the stented group we found an 11,6% incidence of pancreatitis and 26,1% of
      hyperamylasemia. In the primary closure group we found a clear improvement of
      complications and hospital stay. The increased experience of the surgeon and age
      (younger than 75) had a positive impact on mortality and morbidity. CONCLUSIONS:
      Primary closure of the common bile duct after LCBDE seems to be superior to
      closure over a T tube and stents. The learning curve seems to have a positive
      impact on the outcomes making it a safe and reproducible technique especially for
      patients aged under 75.

PMID- 24559590
TI  - Engineering crassulacean acid metabolism to improve water-use efficiency.
AB  - Climatic extremes threaten agricultural sustainability worldwide. One approach to
      increase plant water-use efficiency (WUE) is to introduce crassulacean acid
      metabolism (CAM) into C3 crops. Such a task requires comprehensive systems-level
      understanding of the enzymatic and regulatory pathways underpinning this temporal
      CO2 pump. Here we review the progress that has been made in achieving this goal.
      Given that CAM arose through multiple independent evolutionary origins,
      comparative transcriptomics and genomics of taxonomically diverse CAM species are
      being used to define the genetic 'parts list' required to operate the core CAM
      functional modules of nocturnal carboxylation, diurnal decarboxylation, and
      inverse stomatal regulation. Engineered CAM offers the potential to sustain plant
      productivity for food, feed, fiber, and biofuel production in hotter and drier
      climates. 

PMID- 24559593
TI  - Clostridium difficile infection in Brazil: a neglected problem?
AB  - The epidemiology of Clostridium difficile infection is virtually unknown in
      Brazil. In this prospective study, 8.3% of patients with nosocomial diarrhea were
      found to have toxigenic strains of C difficile in their feces. The relevant risk
      factors for Clostridium difficile infection were receipt of solid organ
      transplantation and septic shock. 

PMID- 24559594
TI  - Development of a urinary-specific antibiogram for gram-negative isolates: impact
      of patient risk factors on susceptibility.
AB  - BACKGROUND: Traditional antibiograms guide clinicians in selecting appropriate
      empiric antimicrobials, but they lack data on syndrome/disease-specific
      susceptibility, isolate location, polymicrobial infections, and patient risk
      factors. The aim of this study was to develop a urinary-specific antibiogram and
      to evaluate the impact of risk factors on antimicrobial susceptibility. METHODS:
      This retrospective descriptive study used culture and susceptibility data from
      January 1 to December 31, 2012. A urinary antibiogram specific for Escherichia
      coli (EC), Proteus mirabilis (PM), Klebsiella pneumoniae (KP), and Pseudomonas
      aeruginosa (PA) was developed. Urinary and standard antibiogram susceptibilities
      were compared. Urinary isolates were then stratified by risk factors-residence
      before admission, age, systemic antimicrobial use for <=30 days, hospitalization
      for <=30 days, and hospital unit-to determine the impact on antimicrobial
      susceptibility. RESULTS: There were 2,284 urinary isolate encounters. Overall
      antimicrobial susceptibility was increased, and the prevalence of extended
      spectrum beta-lactamase-producing isolates was significantly greater (KP, 14% vs
      7% [P = .001]; EC, 13% vs 9% [P < .001]; PM, 18% vs 10% [P = .004]) in the
      urinary antibiogram vs the standard antibiogram. Health care facility residence
      had the greatest impact on susceptibility for all urinary isolates, especially on
      fluoroquinolone susceptibility for EC and PM. CONCLUSIONS: Using a syndromic
      antibiogram and incorporating patient risk factors into susceptibility data may
      be more useful in guiding clinicians in selecting more appropriate empiric
      therapy.

PMID- 24559595
TI  - Cost of isolation: daily cost of isolation determined and cost avoidance
      demonstrated from the overuse of personal protective equipment in an acute care
      facility.
AB  - We determined the prevalence and associated cost of isolation precautions.
      Current census and historic microbiology cultures were assessed for isolation
      appropriateness following national guidelines. Based on patient assessment and
      culture data, isolation was discontinued resulting in 4,087 days of isolation and
      over $141,000 dollars avoided from excess supplies and time.

PMID- 24559596
TI  - Preventing transmission of MRSA: a qualitative study of health care workers'
      attitudes and suggestions.
AB  - BACKGROUND: Health care workers' (HCWs) perceptions and attitudes affect
      implementation of precautions to prevent transmission of drug-resistant pathogens
      such as methicillin-resistant Staphylococcus aureus (MRSA). Identification of
      challenges and barriers to recommended practices is a critical component of
      promoting a safe clinical environment of care. METHODS: Semistructured interviews
      addressed how MRSA affects HCWs, prevention of transmission, and challenges and
      barriers HCWs experience when entering a MRSA isolation room and performing
      appropriate hand hygiene. RESULTS: The purposive sample of 26 acute care HCWs (16
      registered nurses; 1 physician; 6 allied health professionals; and 3 support
      staff) self-selected from 276 responding to a questionnaire on MRSA. Analysis
      identified 18 themes across seven categories. Most participants reported feeling
      responsible for preventing transmission, and having the knowledge and desire to
      do so. However, many also reported challenges to following consistent hand
      hygiene and use of contact precautions. Barriers included patient care demands,
      equipment and environmental issues such as availability of sinks, time pressures,
      the practices of other HCWs, and the need for additional signs indicating which
      patients require contact precautions. CONCLUSIONS: The HCWs reported a need for
      improved clarity of isolation protocols throughout patients' hospital journey,
      additional rooms and staff for isolation patients, improved education and
      communication (including timely and appropriate signage), and an emphasis on
      involving all HCWs in reducing contamination.

PMID- 24559597
TI  - Potential bloodborne pathogen exposure from occult mattress damage.
AB  - A near-miss patient incident involving body fluid seeping from a mattress led to
      a visual inspection of 656 hospital bed mattresses of which 177 were contaminated
      because of occult damage to mattress covers. 

PMID- 24559598
TI  - The role of tissue plasminogen activator use and systemic hypercoagulability in
      central line-associated bloodstream infections.
AB  - BACKGROUND: Central line-associated bloodstream infections (CLABSIs) impact
      patient outcomes and increase cost of hospitalization. In situ thrombus is known
      to promote microbial adhesion and colonization and potentially lead to CLABSI.
      Clinical validation of this theory, adjusting for presence of systemic
      hypercoagulability, is needed. METHODS: This study is a retrospective review of
      all adult and pediatric patients with peripherally inserted central catheter
      placement over a 4-year period at our tertiary care center. Tissue plasminogen
      activator (TPA) use was utilized as indicator for line site thrombus. CLABSIs
      rates were compared in patients with or without TPA use, adjusting for the
      presence of hypercoagulable conditions, age, and severity of illness. RESULTS: A
      total of 3,723 patients with peripherally inserted central catheter lines was
      evaluated, 40% of whom received TPA. The adjusted odds of developing a CLABSI was
      3.59 times greater in those patients who received TPA compared with those who did
      not (95% confidence interval [CI]: 1.86-6.94). Neither severity of illness (odds
      ratio [OR], 1.00; 95% CI: 0.51-1.96) nor primary (OR, 3.41; 95% CI: 0.43-26.7) or
      secondary hypercoagulability (OR, 0.91; 95% CI: 0.44-1.88) were statistically
      associated with a higher risk of infection. CONCLUSION: The use of TPA, as a
      possible indicator in situ thrombus, was associated with a higher risk of
      developing CLABSI. Neither primary nor secondary hypercoagulability was
      correlated with risk of developing CLABSI.

PMID- 24559599
TI  - Effects of white noise and holding on pain perception in newborns.
AB  - This experimental study on newborns was conducted to compare the effects of
      various atraumatic care procedures during an infant's crying response to pain.
      Included in this study were 120 newborns chosen from among healthy infants
      admitted to the Obstetrics Department of Canakkale State Hospital between April
      2010 and June 2010. The patients were divided into three physically homogeneous
      groups. Infants in group 1 were held on the mothers' laps, infants in group 2
      were held on the mother's laps and listened to white noise, and infants in group
      3 lay in their cribs and listened to white noise while undergoing a painful
      procedure. Data collection included the Neonatal Infant Pain Scale, which was
      used to evaluate the behavioral responses to pain during a heel prick blood draw
      and a newborn information sheet developed by the researcher. Changes in cardiac
      and respiratory rates recorded during the invasive procedure were statistically
      significant among the three groups (p < .05). The shortest crying period and the
      lowest behavioral reactions were among those infants lying in their cribs and
      listening to white noise. This group was then followed by the infants who
      listened to white noise while being held by their mothers. The highest behavioral
      reaction was reported by those infants who were held by their mothers but did not
      listen to white noise. According to the results, white noise is an effective
      nonpharmacologic method to control pain, reduce crying time, and positively
      effect vital signs. Therefore, it is recommended that the use of white noise be
      practiced on newborns when they undergo painful procedures. 

PMID- 24559600
TI  - Comparison of the effect of ginger and zinc sulfate on primary dysmenorrhea: a
      placebo-controlled randomized trial.
AB  - Primary dysmenorrhea is common among young women and results in their
      incapacitation; it can be accompanied by various symptoms that can disrupt their
      lives. The aim of this randomized trial was to compare the effect of ginger, zinc
      sulfate, and placebo on the severity of primary dysmenorrhea in young women. One
      hundred and fifty high school students were recruited. The participants were
      divided into three groups. The first group received ginger capsules, the second
      group received zinc sulfate capsules, and the third group received placebo
      capsules. All participants took the medications for four days, from the day
      before the commencement of menstruation to the third day of their menstrual
      bleeding. The severity of dysmenorrhea was assessed every 24 hours by the pain
      visual analog scale. The severity of pain was significantly different between,
      before, and after the intervention in both the ginger and the zinc sulfate groups
      (p < .001). Compared with the placebo receiving group, participants receiving
      ginger and zinc sulfate reported more alleviation of pain during the intervention
      (p < .05). Ginger and zinc sulfate had similar positive effects on the
      improvement of primary dysmenorrheal pain in young women. 

PMID- 24559601
TI  - Y-U can get more out of your Y-V plasty.

PMID- 24559602
TI  - Canadian Association of Radiologists consensus guidelines for the prevention of
      contrast-induced nephropathy: update 2012.
AB  - PURPOSE: Contrast-induced acute kidney injury or contrast-induced nephropathy
      (CIN) is a significant complication of intravascular contrast medium (CM). These
      guidelines are intended as a practical approach to risk stratification and
      prevention. The major risk factor that predicts CIN is pre-existing chronic
      kidney disease. METHODS: Members of the committee represent radiologists and
      nephrologists across Canada. The previous guidelines were reviewed, and an in
      depth up-to-date literature review was carried out. RESULTS: A serum creatinine
      level (SCr) should be obtained, and an estimated glomerular filtration rate
      (eGFR) should be calculated within 6 months in the outpatient who is stable and
      within 1 week for inpatients and patients who are not stable. Patients with an
      eGFR of >= 60 mL/min have an extremely low risk of CIN. The risk of CIN after
      intra-arterial CM administration appears be at least twice that after intravenous
      administration. Fluid volume loading remains the single most important measure,
      and hydration regimens that use sodium bicarbonate or normal saline solution
      should be considered for all patients with GFR < 60 mL/min who receive intra
      arterial contrast and when GFR < 45 mL/min in patients who receive intravenous
      contrast. Patients are most at risk for CIN when eGFR < 30 mL/min. Additional
      preventative measures include the following: avoid dehydration, avoid CM when
      appropriate, minimize CM volume and frequency, avoid high osmolar CM, and
      discontinue nephrotoxic medications 48 hours before administration of CM.

PMID- 24559603
TI  - Evaluation of HIV prevention interventions for people who inject drugs in low-
      and middle-income countries--the current and future state of the art.

PMID- 24559604
TI  - How to build trustworthy hepatitis C services in an opioid treatment clinic? A
      qualitative study of clients and health workers in a co-located setting.
AB  - BACKGROUND: Given the increasing burden of hepatitis C (HCV) related liver
      disease, innovative health care models are required to extend the reach of HCV
      care and treatment. Opioid substitution treatment (OST) clinics are places of
      high HCV prevalence. The OST clinic is a complex environment, quite distinct to
      other health care settings, with punitive regulations and practices, and a client
      population likely to be mistrustful of systems of authority. Nonetheless, trust
      is widely documented as essential to effective therapeutic encounters. This paper
      examines what is required to develop a trustworthy service in a place, the OST
      clinic, described by some critics as a site of "social control". METHODS: In
      depth interviews were conducted with 57 clients and 19 staff from four NSW pilot
      clinics participating in the Australian ETHOS study. RESULTS: Interview data were
      examined using Hall's framework of trust, involving five principle domains:
      fidelity, competence, honest, confidentiality and global trust. 'Honesty' was
      found to be key to participants' establishing trust in the co-located service and
      its staff. However, the clinic site was also found to be a place of rationed
      trust, in which the themes of OST as "ruling peoples' lives" and the fear of
      repercussions resulting from perceived transgressions against clinic rules,
      threatened to over-ride or undermine the development of trust in HCV services.
      Client participants described trusting health workers "to a point". They
      expressed concerns about the fidelity of co-located HCV and OST services and
      described fears of "institutionalised lies" and breaches of confidentiality.
      Anxieties around the latter revealed a sense of "us and them" held by some
      clients, one in which health workers were perceived to "stick together" by
      putting their own interests before those of the clients. DISCUSSION: Although the
      co-location of HCV and opioid treatments makes intuitive policy sense, HCV health
      workers in the OST space may be seen as representatives of a deeply mistrusted
      system. For the effective development of a trustworthy HCV care service, policy
      and practice activities are required to engender trust through clearly
      articulated explanations of service boundaries and the promotion of "success
      stories" through trusted peer networks.

PMID- 24559606
TI  - Correlates of drug use cessation among participants in the Canadian HIV-HCV Co
      infection Cohort.
AB  - BACKGROUND: Ongoing drug use remains a barrier to HIV and HCV treatment. We
      examined the occurrence and correlates of drug use cessation among HIV-HCV co
      infected drug users participating in HIV care. METHODS: Participants from the
      Canadian Co-infection Cohort reporting drug use (injecting drugs and/or smoking
      crack) with at least two follow-up visits were included (n=521 (43%), 1832
      visits). Socio-demographics, behavioural, and health information were collected
      at each six-month visit. Associations with cessation (no drug use since last
      visit) were examined using non-linear mixed effects logistic regression models
      with random intercepts. RESULTS: During follow-up, 361 (69%) participants ceased
      using drugs. Having a fixed address (aOR [adjusted odds ratio] 1.73, CI [95%
      confidence interval] 1.02-2.96) and smoking crack without injecting drugs (aOR
      3.10, CI 2.05-4.71) were positively associated. Living alone (aOR 0.47, CI 0.35
      0.63), current tobacco use (aOR 0.41, CI 0.26-0.64), hazardous alcohol drinking
      (aOR 0.67, CI 0.49-0.91), snorting drugs (aOR 0.52, CI 0.37-0.74), having a
      greater exposure to addiction programmes (aOR 0.88, CI 0.81-0.94), having been
      recruited in Quebec or Nova Scotia (aOR 0.41, CI 0.25-0.66), and British Columbia
      or Alberta (aOR 0.51, CI 0.32-0.82) were negatively associated. Various socio
      demographic (age, education) and health-related (HIV duration, care adherence)
      factors were not associated. CONCLUSION: Drug use cessation among HIV-HCV co
      infected persons is relatively common in this cohort. Stable housing and
      supportive living situations seem to be important facilitators for drug use
      cessation in this population. Greater efforts should be made to retain patients
      in addiction treatment programmes.

PMID- 24559605
TI  - Association of traumatic brain injuries with vomiting in children with blunt head
      trauma.
AB  - STUDY OBJECTIVE: We aimed to determine the prevalence of traumatic brain injuries
      in children who vomit after minor blunt head trauma, particularly when the
      vomiting occurs without other findings suggestive of traumatic brain injury (ie,
      isolated vomiting). We also aimed to determine the relationship between the
      timing and degree of vomiting and traumatic brain injury prevalence. METHODS:
      This was a secondary analysis of children younger than 18 years with minor blunt
      head trauma. Clinicians assessed for history and characteristics of vomiting at
      the initial evaluation. We assessed for the prevalence of clinically important
      traumatic brain injury and traumatic brain injury on computed tomography (CT).
      RESULTS: Of 42,112 children enrolled, 5,557 (13.2%) had a history of vomiting, of
      whom 815 of 5,392 (15.1%) with complete data had isolated vomiting. Clinically
      important traumatic brain injury occurred in 2 of 815 patients (0.2%; 95%
      confidence interval [CI] 0% to 0.9%) with isolated vomiting compared with 114 of
      4,577 (2.5%; 95% CI 2.1% to 3.0%) with nonisolated vomiting (difference -2.3%,
      95% CI -2.8% to -1.5%). Of patients with isolated vomiting for whom CT was
      performed, traumatic brain injury on CT occurred in 5 of 298 (1.7%; 95% CI 0.5%
      to 3.9%) compared with 211 of 3,284 (6.4%; 95% CI 5.6% to 7.3%) with nonisolated
      vomiting (difference -4.7%; 95% CI -6.0% to -2.4%). We found no significant
      independent associations between prevalence of clinically important traumatic
      brain injury and traumatic brain injury on CT with either the timing of onset or
      time since the last episode of vomiting. CONCLUSION: Traumatic brain injury on CT
      is uncommon and clinically important traumatic brain injury is very uncommon in
      children with minor blunt head trauma when vomiting is their only sign or
      symptom. Observation in the emergency department before determining the need for
      CT appears appropriate for many of these children.

PMID- 24559607
TI  - The global epidemiology and burden of psychostimulant dependence: findings from
      the Global Burden of Disease Study 2010.
AB  - AIMS: To estimate the global prevalence of cocaine and amphetamine dependence and
      the burden of disease attributable to these disorders. METHODS: An
      epidemiological model was developed using DisMod-MR, a Bayesian meta-regression
      tool, using epidemiological data (prevalence, incidence, remission and mortality)
      sourced from a multi-stage systematic review of data. Age, sex and region
      specific prevalence was estimated for and multiplied by comorbidity-adjusted
      disability weightings to estimate years of life lost to disability (YLDs) from
      these disorders. Years of life lost (YLL) were estimated from cross-national
      vital registry data. Disability-adjusted life years (DALYs) were estimated by
      summing YLDs and YLLs in 21 regions, by sex and age, in 1990 and 2010. RESULTS:
      In 2010, there were an estimated 24.1 million psychostimulant dependent people:
      6.9 million cocaine and 17.2 million amphetamines, equating to a point prevalence
      of 0.10% (0.09-0.11%) for cocaine, and 0.25% (0.22-0.28%) for amphetamines. There
      were 37.6 amphetamine dependence DALYs (21.3-59.3) per 100,000 population in 2010
      and 15.9 per 100,000 (9.3-25.0) cocaine dependence DALYs. There were clear
      differences between amphetamines and cocaine in the geographic distribution of
      crude DALYs. Over half of amphetamine dependence DALYs were in Asian regions
      (52%), whereas almost half of cocaine dependence DALYs were in the Americas (44%,
      with 23% in North America High Income). CONCLUSION: Dependence upon
      psychostimulants is a substantial contributor to global disease burden; the
      contribution of cocaine and amphetamines to this burden varies dramatically by
      geographic region. There is a need to scale up evidence-based interventions to
      reduce this burden.

PMID- 24559608
TI  - Biochemical markers of pollutant responses in macrozoobenthos from the White Sea:
      intracellular proteolysis.
AB  - Coastal environments of Kandalaksha Gulf in the White Sea (Russia) despite nature
      conservation efforts are heavily influenced by human activities. Biological
      effects of complex environmental pollution, including organic substances, heavy
      metals, and oil hydrocarbons, were assessed in widely distributed marine
      invertebrates, Gammarus duebeni (Crustacea, Amphipoda) and Mytilus edulis
      (Mollusca, Bivalvia), collected from a series of anthropogenically-impacted areas
      and distanced reference sites in Kandalaksha Gulf. The parameters of
      intracellular protein degradation pathways such as cytosol calpain system and
      lysosomal cathepsins B (CatB) and cathepsin D (CatD) were studied. The response
      reactions observed in invertebrates vary in specificity and ranged from adaptive
      to destructive depending on the total contaminant level and the nature of
      predominant pollutant. The ecological relevance of studied parameters as
      biomarkers was confirmed by their ability to indicate both expose to pollutants
      and adverse effects at the organism level. 

PMID- 24559609
TI  - Psychological distress in children with developmental coordination disorder and
      attention-deficit hyperactivity disorder.
AB  - This study explored whether or not a population-based sample of children with
      developmental coordination disorder (DCD), with and without comorbid attention
      deficit/hyperactivity disorder (ADHD), experienced higher levels of psychological
      distress than their peers. A two-stage procedure was used to identify 244
      children: 68 with DCD only, 54 with ADHD only, 31 with comorbid DCD and ADHD, and
      91 randomly selected typically developing (TD) children. Symptoms of depression
      and anxiety were measured by child and parent report. Child sex and caregiver
      ethnicity differed across groups, with a higher ratio of boys to girls in the
      ADHD only group and a slightly higher proportion of non-Caucasian caregivers in
      the TD group. After controlling for age, sex, and caregiver ethnicity, there was
      significant variation across groups in both anxiety (by parent report,
      F(3,235)=8.9, p<0.001; by child report, F(3,236)=5.6, p=0.001) and depression
      (parent report, F(3,236)=23.7, p<0.001; child report, F(3,238)=9.9, p<0.001). In
      general, children in all three disorder groups had significantly higher levels of
      symptoms than TD children, but most pairwise differences among those three groups
      were not significant. The one exception was the higher level of depressive
      symptoms noted by parent report in the ADHD/DCD group. In conclusion, children
      identified on the basis of motor coordination problems through a population-based
      screen showed significantly more symptoms of depression and anxiety than
      typically developing children. Children who have both DCD and ADHD are
      particularly at heightened risk of psychological distress. 

PMID- 24559610
TI  - Sample preparation to observe the straight and flat posture of silkworm embryo
      under scanning electron microscopy via glycerol substitution method.
AB  - In the preparation process for scanning electron microscopy (SEM), flexed
      silkworm embryos typically assume several curled shapes with irregular postures
      that obscure morphological details during SEM observation. We describe a
      preparation technique based on glycerol substitution for better SEM visualization
      of straight and flat silkworm embryos. Glycerol has high viscosity, low vapor
      pressure, and sufficient electrical conductivity. Silkworm embryos were
      infiltrated with glycerol and arranged in a straight posture or flattened using a
      cover slip. Samples were directly observed by SEM without additional dehydration,
      drying, or coating procedures. The complete ventral side could be easily viewed
      in one image. Recoating alleviated the charging phenomenon. This represents a
      simple method for preparation of straight and flat samples from curled biological
      specimens for SEM observation. 

PMID- 24559611
TI  - Accompanying DCIS in breast cancer patients with invasive ductal carcinoma is
      predictive of improved local recurrence-free survival.
AB  - BACKGROUND: Ductal carcinoma in situ (DCIS) often accompanies invasive ductal
      carcinoma (IDC). The presence of co-existing DCIS is postulated to present as a
      less aggressive phenotype than IDC alone. PATIENTS AND METHODS: Patients
      diagnosed with hormone receptor-positive breast cancer receiving mastectomy were
      evaluated. Only patients without adjuvant radio- and chemotherapy were included
      to decrease treatment bias on local recurrence (LR). RESULTS: Of 2239 breast
      cancer patients, 198 fulfilled the inclusion criteria. The overall LR rate was
      11.6%. Tumor stage (p = 0.002), nodal status (pN2 vs. pN0, p = 0.023) and pure
      IDC compared with IDC-DCIS (p = 0.029) were multivariate independent factors for
      increased LR risk. Patients with IDC-DCIS were significantly younger (p < 0.001),
      had smaller tumors (p = 0.001), less lymph node involvement (p = 0.012). The LR
      rate was significantly increased in patients with pure IDC (p = 0.012). The time
      to distant metastases was decreased in patients with pure IDC compared with that
      observed in patients with IDC-DCIS (log rank = 0.030). CONCLUSION: Invasive
      ductal carcinoma accompanied by DCIS is associated with lower LR. The prognostic
      value of co-existing DCIS in the adjuvant decision-making process may be
      considered a new independent prognostic marker. This finding needs further
      studies to evaluate its usefulness in premenopausal women.

PMID- 24559612
TI  - Viewing condition dependence of the gaze-evoked nystagmus in Arnold Chiari type 1
      malformation.
AB  - Saccadic eye movements rapidly shift gaze to the target of interest. Once the
      eyes reach a given target, the brainstem ocular motor integrator utilizes
      feedback from various sources to assure steady gaze. One of such sources is
      cerebellum whose lesion can impair neural integration leading to gaze-evoked
      nystagmus. The gaze evoked nystagmus is characterized by drifts moving the eyes
      away from the target and a null position where the drifts are absent. The extent
      of impairment in the neural integration for two opposite eccentricities might
      determine the location of the null position. Eye in the orbit position might also
      determine the location of the null. We report this phenomenon in a patient with
      Arnold Chiari type 1 malformation who had intermittent esotropia and horizontal
      gaze-evoked nystagmus with a shift in the null position. During binocular
      viewing, the null was shifted to the right. During monocular viewing, when the
      eye under cover drifted nasally (secondary to the esotropia), the null of the
      gaze-evoked nystagmus reorganized toward the center. We speculate that the output
      of the neural integrator is altered from the bilateral conflicting eye in the
      orbit position secondary to the strabismus. This could possibly explain the
      reorganization of the location of the null position. 

PMID- 24559613
TI  - Introduction: gynecology surgery and preservation of fertility.
AB  - This Views and Reviews includes three examples of a collaborative approach
      between surgery and reproductive medicine. Infertility surgery has developed into
      a subspecialty requiring the participation of both surgeons and reproductive
      medicine specialists before the decision to operate is made. 

PMID- 24559614
TI  - Relationship between ovarian cysts and infertility: what surgery and when?
AB  - The relationship between ovarian cysts and infertility is a subject of debate,
      mainly because it is difficult to determine the real impact of the cyst and its
      treatment on later fertility. For a long time it was hoped that surgical
      treatment could prevent potential complications (such as rupture or malignancy).
      For presumed benign ovarian tumors, fertility sparing should be the main concern.
      The goal of this survey of current knowledge on the subject is to thoroughly
      explore the potential relationship between cysts, their treatment, and
      infertility. Our study is based on a review of the literature dealing with the
      epidemiology of ovarian cysts and the effects of their surgical management in
      relation to infertility. Analysis of the epidemiologic data, drawn mainly from
      comparative studies and cohorts, shows that the role of cysts in infertility is
      controversial and that the effects of surgical treatment are often more harmful
      than the cyst itself to the ovarian reserve. Surgery does not seem to improve
      pregnancy rates. When a surgical option is nonetheless chosen, a conservative
      laparoscopic approach is more suitable. Besides excision, sclerotherapy and
      plasma vaporization are promising, offering a greater preservation of the ovarian
      parenchyma, especially in endometriomas. These techniques must be better defined.
      The context of the infertility is essential, and surgeons and specialists in
      reproductive medicine should decide management jointly. 

PMID- 24559615
TI  - Treatment of ectopic pregnancies in 2014: new answers to some old questions.
AB  - Over the past 20 years, a substantial body of research has accumulated about
      ectopic pregnancy, especially about its epidemiology, risk factors, and
      diagnosis. Nonetheless, the care of women with these pregnancies remains a topic
      of debate, and no consensus or guidelines exist to clarify the optimal treatment
      choices. This review revisits the four primary treatments for ectopic pregnancy
      and defines and details the concept of "activity," which guides the indications
      for each treatment. Recent findings of no difference in fertility during the 2
      years after an ectopic pregnancy have answered some old questions and raised new
      ones for determining the optimal management of ectopic pregnancies. Most
      especially, they allow the consideration and weighing of a wider range of
      factors, including the woman's own preferences as well as efficacy and the
      monitoring time until recovery.

PMID- 24559616
TI  - Robot-assisted laparoscopy for infertility treatment: current views.
AB  - To determine the interest of using robotic laparoscopic surgery in the management
      of female infertility, we reviewed our own activity and searched the Medline
      database for publications on robotic technology in infertility surgery, with the
      use of the following search words: robotic laparoscopy, tubal anastomosis,
      myomectomy, deep infiltrating endometriosis, and adnexal surgery. Robot-assisted
      laparoscopic surgery has seen rapid progression over the past few years. It has
      been mostly used for myomectomy, proximal tubal reanastomosis, and deep
      endometriosis surgery. Despite its increased range of indications, no randomized
      control studies are available. The place of robotic surgery in the management of
      infertility remains undetermined. 

PMID- 24559617
TI  - Female age-related fertility decline. Committee Opinion No. 589.
AB  - The fecundity of women decreases gradually but significantly beginning
      approximately at age 32 years and decreases more rapidly after age 37 years.
      Education and enhanced awareness of the effect of age on fertility are essential
      in counseling the patient who desires pregnancy. Given the anticipated age
      related decline in fertility, the increased incidence of disorders that impair
      fertility, and the higher risk of pregnancy loss, women older than 35 years
      should receive an expedited evaluation and undergo treatment after 6 months of
      failed attempts to conceive or earlier, if clinically indicated. In women older
      than 40 years, more immediate evaluation and treatment are warranted. 

PMID- 24559618
TI  - Adolescents, pregnancy, and mental health.
AB  - STUDY OBJECTIVE: Pregnancy during adolescence is a risk factor for adverse
      medical and psychosocial outcomes, including psychiatric illness. Psychiatric
      illness is linked with obstetric complications along with impaired maternal
      functioning in the postpartum period. This article provides a comprehensive
      review of the research examining the intersection of psychopathology and
      adolescent pregnancy and the postpartum period. DESIGN: A literature search was
      conducted using PubMed (Medline), PsycINFO, and CINAHL for articles published
      between 1990 and 2013 that examined depression, anxiety, bipolar disorder, and
      psychosis during pregnancy and the postpartum period in adolescents age 21 years
      or younger. Articles were selected that covered the following topics: Prevalence
      or incidence, comorbidity, psychosocial correlates, birth outcomes, parenting,
      child outcomes, and psychosocial treatment. Forty articles were found and
      reviewed. RESULTS: There is a substantial research base examining self-reported
      depressive symptoms in adolescents during pregnancy and the postpartum period.
      Existing research suggests that pregnant and parenting adolescents are at greater
      risk for experiencing depressive symptoms than pregnant and postpartum adult
      women. Depression in the perinatal period is also a risk factor for substance and
      alcohol abuse and a harsher parenting style in adolescents. Areas for future
      research in this population include investigating the prevalence, psychosocial
      correlates, and outcomes of clinically diagnosed Major Depressive Disorder,
      developing and empirically validating psychotherapeutic treatments, and focusing
      upon other psychiatric diagnoses such as bipolar disorder, anxiety, and
      psychosis.

PMID- 24559619
TI  - Intermittent low-dose finasteride administration is effective for treatment of
      hirsutism in adolescent girls: a pilot study.
AB  - STUDY OBJECTIVE: Hirsutism has negative impact on adolescent psychosocial
      development for both cosmetic and endocrine reasons. This study evaluated the
      effectiveness of a new intermittent, low-dose finasteride regimen consisting of
      2.5 mg of drug given every 3 days (1 day of treatment, 2 days of drug withdrawal)
      for 6 months in girls with hirsutism by polycystic ovarian syndrome (PCOS) or
      idiopathic hirsutism (IH). DESIGN AND PARTICIPANTS: Twenty-eight girls (15-19 y
      old) with hirsutism were randomly assigned to 2 treatment groups and treated for
      6 months. Fourteen patients (7 with IH, 7 with PCOS) received finasteride;
      fourteen patients (7 with IH, 7 with PCOS) received placebo. Hirsutism score
      (HS), clinical, and hormonal effects were compared between the 2 groups. RESULTS:
      In patients treated with finasteride, the HS value at 6 months was 52.9% lower
      than that observed at baseline in girls with IH, and 52.8% lower in girls with
      PCOS (P < .0001 for both). Similarly, the 3alpha-17 beta-androstenediol
      glucuronide serum levels were decreased by 34.8% in patients with IH, and by
      47.5% in patients with PCOS (P < .0001, respectively). Finasteride treatment was
      well tolerated and did not alter values of BMI, serum levels of sexual hormones,
      metabolic parameters related to liver and kidney function as well as glycemic and
      lipidic asset. CONCLUSIONS: A low-dose of finasteride, given every 3 days,
      reduces the HS in young patients affected by PCOS or IH. Compared with
      conventional continuous finasteride administration, the intermittent low-dose
      regimen has similar efficacy with the advantage to be safer and less expensive.

PMID- 24559620
TI  - Implementation of a self-care of heart failure program among home-based clients.
AB  - Heart failure is the most common admission in hospitals among Medicare recipients
      aged 65 years or older. Self-care management of heart failure has been reported
      to decrease heart failure hospital admission rates. The purpose of this evidence
      based practice project was to examine how a self-care of heart failure program
      (Heart Failure Self-care to Success) impacts hospital admissions and patient
      perceptions of self-care management. Heart Failure Self-care to Success (HF S2S)
      was successfully implemented with 18 participants by nurse practitioners in a
      house call practice. Six months following implementation of the self-care of
      heart failure program no heart failure admissions occurred among participants and
      a significant increase in their self-care of heart failure behaviors (p < .01)
      was reported by participants. Nurse practitioners using HF S2S can decrease
      health care costs and improve self-care behaviors in the older, homebound heart
      failure patient. Further testing of HF S2S is recommended in different practice
      settings, sample populations, and geographic locations.

PMID- 24559622
TI  - Survey response rate, a guide for readers and authors.

PMID- 24559621
TI  - Cognitive interventions for older adults: does approach matter?
AB  - A group training format was compared to one-to-one training in a cognitive
      intervention, Reasoning Exercises in Assisted Living (REAL), designed for elderly
      Assisted Living residents. Change scores on problem solving and functional
      outcomes were compared between participants in each group. In participants
      trained individually (n = 29), scores increased post-intervention on the Every
      Day Problems Test for Cognitively Challenged Elders (EPCCE; d = 3.10, p < 0.01)
      and the Direct Assessment of Functional Status (DAFS; d = 3.52, p < 0.001), at a
      cost of $132 per person. Participants (N = 4) in the group format REAL had mean
      score increases of 2.75 points on the EPCCE and 3.5 on the DAFS, at a cost of
      $25.60 per person. Additional testing is warranted to verify the group effects
      due to the limited size of the sample. Relative costs and effects of various
      training formats are important to consider when developing, testing, and
      disseminating interventions targeting older adults.

PMID- 24559623
TI  - Comparison of screw trajectory on stability of oblique scaphoid fractures: a
      mechanical study.
AB  - PURPOSE: To determine whether a screw placed perpendicular to the fracture line
      in an oblique scaphoid fracture will provide fixation strength that is comparable
      with that of a centrally placed screw. METHODS: Oblique osteotomies were made
      along the dorsal sulcus of 8 matched pairs of cadaveric scaphoids. One scaphoid
      from each pair was randomized to receive a screw placed centrally down the long
      axis. In the other scaphoid, a screw was placed perpendicular to the osteotomy.
      Each scaphoid underwent cyclic loading from 80 N to 120 N at 1 Hz. Cyclic loading
      was carried out until 2 mm of fracture displacement occurred or 4,000 cycles was
      reached. The specimens that reached the 4,000-cycle limit were then loaded to
      failure. Screw length, number of cycles, and load to failure were compared
      between the groups. RESULTS: We found no difference in number of cycles or load
      to failure between the 2 groups. Screws placed perpendicular to the fracture line
      were significantly shorter than screws placed down the central axis. CONCLUSIONS:
      A perpendicularly placed screw provides equivalent strength to one placed along
      the central axis. CLINICAL RELEVANCE: Compared with a screw placed centrally in
      an oblique scaphoid fracture, a screw placed perpendicular to the fracture line
      allows the use of a shorter screw without sacrificing strength of fixation.

PMID- 24559624
TI  - Long-term results of Swanson silicone arthroplasty for proximal interphalangeal
      joint osteoarthritis.
AB  - PURPOSE: To review the long-term outcome of the Swanson silicone arthroplasty in
      the osteoarthritic proximal interphalangeal (PIP) joint at a single institution.
      METHODS: We identified 51 patients who had undergone PIP joint Swanson silicone
      arthroplasty for osteoarthritis and included in the study only those 22 patients
      (38 joints) who responded and could follow up. These patients returned for follow
      up evaluation at an average of 10 years (range, 2-24 y). Subjective outcomes were
      assessed using the Quick-Disabilities of the Arm, Shoulder, and Hand
      questionnaire, visual analog pain scale, and Likert questionnaire scores.
      Clinical and radiographic objective data were collected by measuring range of
      motion and coronal plane deformation and assessing final radiographs. RESULTS:
      Silicone arthroplasty at the PIP joint consistently provided pain relief in
      patients who returned for follow-up. The average Quick-Disabilities of the Arm,
      Shoulder, and Hand score was 17 and the average pain visual analog scale score
      was 0.4. The Likert questionnaire revealed that on average, patients agreed or
      strongly agreed that they would have surgery again, would recommend surgery to
      another patient, and were satisfied at an average of 10 years after surgery.
      Patients had neutral responses when they rated appearance, functional
      improvement, and range of motion. Objectively, range of motion (flexion arc of 50
      degrees ) did not significantly change from the preoperative flexion arc (55
      degrees ). Radiographically, 31 implants had deformation, including 21 with
      implant fracture. There were 3 revisions for symptomatic implant fractures and 1
      implant was removed for infection. There was no correlation between radiographs
      and satisfaction. CONCLUSIONS: Despite unchanged range of motion and considerable
      radiographic implant deformation or fracture, patients obtained consistent pain
      relief and satisfaction. With an implant survivorship of 90% at average of 10
      years postoperatively, silicone implant arthroplasty remains our treatment of
      choice for the symptomatic osteoarthritic PIP joint. TYPE OF STUDY/LEVEL OF
      EVIDENCE: Therapeutic IV.

PMID- 24559625
TI  - Complete pseudoepiphyses with associated enhanced growth in hands and feet: a
      report of 2 siblings--case report.
AB  - We present 2 siblings with multiple complete pseudoepiphyses in their hands and
      feet with associated symptomatic enhanced growth. Physical examination of the 6
      year-old boy revealed long slender fingers and hyperplastic great toes.
      Radiography showed complete pseudoepiphyses in the first metacarpals, proximal
      and middle phalanges of the hands, and proximal phalanges of the feet. The
      patient's younger brother had a similar phenotype with slightly milder functional
      complaints. Genetic analysis did not reveal an underlying syndrome in these
      siblings. 

PMID- 24559626
TI  - The effect of patient involvement in surgical decision making for carpal tunnel
      release on patient-reported outcome.
AB  - PURPOSE: To investigate whether patient-reported outcomes are different according
      to patients' preference or experience in surgical decision making for carpal
      tunnel release. METHODS: We preoperatively surveyed 85 patients who underwent
      carpal tunnel release regarding their preferred role in the process of surgical
      decision making and assessed their experienced role in the actual decision making
      6 months after surgery using a Control Preference Scale. For patient-reported
      surgical outcomes, we used the Disabilities of the Arm, Shoulder, and Hand
      questionnaire. We compared these outcomes with those of patients having different
      preferences or experiences in surgical decision making and also compared the
      outcomes according to whether the preferred roles match the experienced roles.
      RESULTS: The Disabilities of the Arm, Shoulder, and Hand scores were not
      significantly different between patients with different preferences for
      involvement in decision making for surgery or between those with different
      experiences in the actual decision making. However, those who experienced the
      same level of involvement as they had preferred were found to have better
      Disabilities of the Arm, Shoulder, and Hand scores than those who experienced a
      more active role or a more passive role than they had preferred. CONCLUSIONS:
      This study demonstrates that patient-reported outcomes were not different between
      those with different preferences or experiences in surgical decision making for
      carpal tunnel release. However, this study suggests that patients whose
      experience in decision making matched with their preference may have better
      subjective outcomes after carpal tunnel release. This suggests that patients with
      carpal tunnel syndrome may benefit from physicians' efforts of identifying
      patients' preferences for involvement in decision making and matching the
      identified preferences to the decision-making process. TYPE OF STUDY/LEVEL OF
      EVIDENCE: Prognostic II.

PMID- 24559627
TI  - High-speed burr debulking of digital calcinosis cutis in scleroderma patients.
AB  - PURPOSE: To evaluate the functional outcome after removal of digital calcinosis
      cutis in patients with scleroderma using a high-speed burr. METHODS: A
      retrospective analysis was performed of 9 consecutively enrolled scleroderma
      patients who underwent surgery by the senior author. A debulking procedure using
      a high-speed micro-burr to soften and express calcific material in digits was
      performed. Demographics, complications, recurrence, and postoperative functional
      outcome measurements including the Disabilities of the Arm, Shoulder, and Hand
      questionnaire, the Michigan Hand Questionnaire, a study-specific questionnaire, a
      visual analog scale, and the Short Form-12 were collected. RESULTS: Mean follow
      up time was 2 years. Four of 9 patients were very or somewhat satisfied with the
      procedure. Eight complications were recorded in 6 patients, including weakness,
      decreased motion, numbness, and superficial wound infection. The mean
      Disabilities of the Arm, Shoulder, and Hand score in patients who would have
      surgery again was 27 (4 of 9), versus 54 (5 of 9) for those who would not. Two
      patients had no recurrence. There were 7 cases of recurrence; 3 patients had late
      recurrence to a small degree, 3 had early complete recurrence, and 1 had
      recurrence at an unknown onset. No patient reported complete resolution of
      calcinosis. Patient satisfaction appeared inversely correlated to the number of
      digits involved. CONCLUSIONS: Patients with discrete areas of calcinosis cutis,
      including those with 1 or 2 digits affected, did much better than patients with
      diffuse disease and multiple affected digits. Patients should be counseled that
      the benefit might be more limited than previously reported, and recurrence is
      likely. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

PMID- 24559628
TI  - Retrograde arterialized free venous flaps for the reconstruction of the hand:
      review of 14 cases.
AB  - PURPOSE: Although the literature is encouraging with regard to the survival rate
      of arterialized free venous flaps, previously reported difficulty in healing
      owing to early venous congestion and subsequent epidermolysis continues to
      prevent their widespread application. We report 14 arterialized free venous flaps
      for primary reconstruction of the hand, with inflow in the arterialized vein
      running against the valves. METHODS: Between February 2010 and May 2012, we
      performed 14 arterialized free venous flaps, each of which included at least 2
      veins running in parallel. The arterialized vein was anastomosed in a retrograde
      manner, with the inflow running against the valves. All flaps were customized
      with regard to dimension, shape, quality of skin, pedicle length, vessel size,
      inclusion of additional anatomical structures, and donor site. The flaps were
      used to cover small, medium, and large defects; 2 flaps were larger than 100
      cm(2). Three flaps were injected with indocyanine green on the table after
      harvesting, to visualize the vascular tree of the flap. These 3 flaps were then
      monitored with systemic indocyanine green injection and an infrared camera for 3
      days postoperatively. RESULTS: All but 1 flap survived. Venous congestion and
      epidermolysis were observed in 2 small flaps. The flaps injected with indocyanine
      green displayed a ramified vascular tree with no arteriovenous flow-through
      phenomenon. CONCLUSIONS: Arterialized free venous flaps with retrograde arterial
      flow offer thin and pliable coverage that fits easily around the contours of the
      hand. They are easy to harvest, with little donor site morbidity. Tendons or
      nerves can be incorporated for reconstruction of composite defects. CLINICAL
      RELEVANCE: Our series suggests the possibility of routine use of a free venous
      flap with retrograde arterial flow for reconstruction of the hand. TYPE OF
      STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

PMID- 24559629
TI  - Traumatic flexor digitorum superficialis and A2-A3 pulley rupture: case report.
AB  - We present a case of simultaneous traumatic rupture of the flexor digitorum
      superficialis tendon and the A2 and A3 flexor tendon pulleys. Excision of the
      flexor digitorum superficialis tendon and reconstruction of the pulleys led to
      restoration of function. 

PMID- 24559630
TI  - The influence of patient insurance status on access to outpatient orthopedic care
      for flexor tendon lacerations.
AB  - PURPOSE: To determine the effect of patient insurance status on access to
      outpatient orthopedic care for acute flexor tendon lacerations. METHODS: The
      research team contacted 100 randomly chosen orthopedic surgery practices in North
      Carolina by phone on 2 different occasions separated by 3 weeks. The research
      team attempted to obtain an appointment for a fictitious 28-year-old man with an
      acute flexor tendon laceration. Insurance status was presented as Medicaid in 1
      call and private insurance in the other call. Ability of an office to schedule an
      appointment was recorded. RESULTS: Of the 100 practices, 13 were excluded because
      they did not perform hand surgery, which left 87 practices. The patient in the
      scenario with Medicaid was offered an appointment significantly less often (67%)
      than the patient in the scenario with private insurance (82%). The odds of the
      patient with private insurance obtaining an appointment were 2.2 times greater
      than the odds of the Medicaid patient obtaining an appointment. The Medicaid
      patient was more likely not to be offered an appointment owing to the lack of a
      hand surgeon at a practice (28% of appointment denials) than privately insured
      patients (13% of appointment denials). CONCLUSIONS: For patients with acute
      flexor tendon lacerations, insurance status has an important role in the ability
      to obtain an orthopedic clinic appointment. We found that patients with Medicaid
      have more barriers to accessing care for a flexor tendon laceration than patients
      with private insurance. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic II.

PMID- 24559631
TI  - Commentary on "the influence of patient insurance status on access to outpatient
      orthopedic care for flexor tendon lacerations".

PMID- 24559632
TI  - The clinical implications of the oblique retinacular ligament.
AB  - The oblique retinacular ligament originates from the flexor tendon sheath,
      courses past the proximal interphalangeal joint, and merges with the lateral
      extensor tendon. There has been disagreement regarding the contribution of the
      oblique retinacular ligament to coordinated movements between the proximal and
      distal interphalangeal joints. Landsmeer postulated that it acts as a dynamic
      tenodesis that tightens with proximal interphalangeal joint extension, causing
      obligatory distal interphalangeal joint extension. However, studies have shown
      that the oblique retinacular ligament is variably present and often attenuated,
      which diminishes its presumed role in finger movement. Despite this, the concept
      of a checkrein linking interphalangeal joint motion heralded the development of
      effective and reproducible surgical interventions for swan-neck and mallet
      deformities. This article examines the controversy regarding the existence of the
      oblique retinacular ligament, its plausible functionality, and clinical
      implications in the practice of hand surgery. 

PMID- 24559633
TI  - Orthoses for trapeziometacarpal arthrosis.

PMID- 24559634
TI  - Lower trapezius transfer for shoulder external rotation in patients with
      paralytic shoulder.
AB  - Restoration of shoulder external rotation in patients with paralytic shoulder is
      very challenging. When nerve repair and/or transfer fails, or if patients present
      late after injury such that nerve reconstruction is not possible, tendon transfer
      to restore shoulder external rotation becomes the main option. Good outcome has
      been reported with lower trapezius transfer to the infraspinatus to restore
      shoulder external rotation in patients with paralytic shoulder. The purpose of
      this manuscript is to describe the surgical technique of this transfer. 

PMID- 24559635
TI  - Ulnar tunnel syndrome.
AB  - Ulnar neuropathy at or distal to the wrist, the so-called ulnar tunnel syndrome,
      is an uncommon but well-described condition. However, diagnosis of ulnar tunnel
      syndrome can be difficult. Paresthesias may be nonspecific or related to
      coexisting pathologies, such as carpal tunnel syndrome, cubital tunnel syndrome,
      thoracic outlet syndrome, C8-T1 radiculopathy, or peripheral neuropathy, which
      makes accurate diagnosis challenging. The advances in electrodiagnosis,
      ultrasonography, computed tomography, and magnetic resonance imaging have
      improved the diagnostic accuracy. This article offers an updated view of ulnar
      tunnel syndrome as well as its etiologies, diagnoses, and treatments. 

PMID- 24559636
TI  - Radial head dislocation during proximal radial shaft osteotomy.
AB  - The following case report describes a 48-year-old female patient with a
      longstanding both-bone forearm malunion, who underwent osteotomies of both the
      radius and ulna to improve symptoms of pain and lack of rotation at the wrist.
      The osteotomies were templated preoperatively. During surgery, after performing
      the planned radial shaft osteotomy, the authors recognized that the radial head
      was subluxated. The osteotomy was then revised from an opening wedge to a closing
      wedge with improvement of alignment and rotation. The case report discusses the
      details of the operation, as well as ways in which to avoid similar shortcomings
      in the future. 

PMID- 24559637
TI  - Decreased expression of microRNA-200b is an independent unfavorable prognostic
      factor for glioma patients.
AB  - BACKGROUND AND AIM: As a member of the microRNA (miR)-200 family, miR-200b has
      been recognized as one of the fundamental regulators of epithelial-mesenchymal
      transition, chemosensitivity, cell proliferation, and cell cycle. Especially in
      glioma, miR-200b targets the CREB1 gene and suppresses the tumor cell growth in
      vitro. However, its involvement in human glioma has not yet been determined. The
      aim of this study was to investigate the clinical significance of miR-200b
      expression in this disease. METHODS: miR-200b expression in 266 pairs of human
      gliomas and matched nonneoplastic brain tissues was measured by real-time
      quantitative RT-PCR assay. RESULTS: Compared with nonneoplastic brain tissues,
      the expression level of miR-200b was significantly decreased in glioma tissues
      (tumor vs. normal: 2.87 +/- 2.05 vs. 8.78 +/- 2.50, P<0.001). Of 266 patients
      with gliomas, 166 (62.41%) were in low miR-200b expression group. In addition, we
      found that the glioma tissues from high-grade tumors (grade III and IV) had much
      lower miR-200b expression than glioma tissues from low grade tumors (grade I and
      II). Moreover, the expression level of miR-200b was positively correlated with
      Karnofsky performance status (KPS) scores of glioma tissues. The results of a 60
      month follow-up in 266 glioma patients further demonstrated that lower miR-200b
      expression was correlated with worse progression-free survival and overall
      survival in the patients with grade III and IV gliomas. Both univariate and
      multivariate analyses revealed that miR-200b was an independent prognostic
      indicator for glioma. CONCLUSION: These findings prove that the decreased
      expression of miR-200b may be associated with malignant tumor progression and
      poor prognosis in patients with gliomas, suggesting the potential role of miR
      200b in glioma management. miR-200b may be a novel and valuable signature for
      predicting the clinical outcome of patients with gliomas.

PMID- 24559638
TI  - Zwitterionic fusion in hydrogels and spontaneous and time-independent self
      healing under physiological conditions.
AB  - The biomedical applications of current self-healing materials are largely impeded
      by their healing conditions, which usually require heating, UV exposure or harsh
      pH environments. At the same time, for very few existing spontaneously self
      healing materials, healing can only be achieved immediately after rupture occurs.
      Here, we developed a spontaneously healing material, driven by a new mechanism,
      "zwitterionic fusion", which is repairable independent of time after damage under
      physiological conditions. We also tested the anti-fatigue property of this
      zwitterionic hydrogel. Furthermore, we utilized this zwitterionic fusion to link
      different cell-hydrogel constructs together. 

PMID- 24559640
TI  - The impact of influenza vaccination on hospitalizations and mortality among frail
      older people.
AB  - OBJECTIVES: The objective of this study was to evaluate the benefits of influenza
      vaccination against hospitalization and mortality on frail elderly people.
      DESIGN: The design was a population-based retrospective cohort study. SETTING:
      Taiwan's National Health Insurance claims data. PARTICIPANTS: Participants were
      5063 frail seniors, followed up for four years. MEASUREMENTS: Measurements
      included age, gender, socioeconomic status, living areas, use of annual health
      examinations, comorbid conditions, use of influenza vaccine, frailty as defined
      by the Adjusted Clinical Group, hospitalization, and mortality in the observation
      period. The efficacy was presented as comparing ever versus never vaccinated
      people during the entire study period without regard to seasons. RESULTS:
      Compared with those without influenza vaccination, vaccinated elderly individuals
      were younger, more likely to be men, have higher socioeconomic status, live in
      rural areas, have a higher rate of receiving a health examination, and have
      similar medical conditions. In the Cox proportional hazards analysis, influenza
      vaccination reduced by 7% the risk of hospitalization (95% confidence interval
      [CI] 0.86-0.99) and by 44% the risk of mortality (95% CI 0.51-0.62). CONCLUSION:
      Influenza vaccination was effective against hospitalization and mortality among
      the frail elderly. These results uphold the current universal influenza
      vaccination policy, and encourage policymakers to adopt strategies to improve
      vaccination use.

PMID- 24559639
TI  - Peripheral nerve morphogenesis induced by scaffold micropatterning.
AB  - Several bioengineering approaches have been proposed for peripheral nervous
      system repair, with limited results and still open questions about the underlying
      molecular mechanisms. We assessed the biological processes that occur after the
      implantation of collagen scaffold with a peculiar porous micro-structure of the
      wall in a rat sciatic nerve transection model compared to commercial collagen
      conduits and nerve crush injury using functional, histological and genome wide
      analyses. We demonstrated that within 60 days, our conduit had been completely
      substituted by a normal nerve. Gene expression analysis documented a precise
      sequential regulation of known genes involved in angiogenesis, Schwann
      cells/axons interactions and myelination, together with a selective modulation of
      key biological pathways for nerve morphogenesis induced by porous matrices. These
      data suggest that the scaffold's micro-structure profoundly influences cell
      behaviors and creates an instructive micro-environment to enhance nerve
      morphogenesis that can be exploited to improve recovery and understand the
      molecular differences between repair and regeneration. 

PMID- 24559641
TI  - Prevalence and correlates of cardiovascular medication use among nursing home
      residents with ischemic heart disease: results from the SHELTER study.
AB  - OBJECTIVES: Despite being the highest group of users of many medications, older
      individuals remain underrepresented in clinical trials. This leaves a gap in
      evidence to guide management of many conditions, such as ischemic heart disease
      (IHD), in this population. This study aimed to describe factors associated with
      IHD medication use among nursing home residents in 7 European countries and
      Israel to depict challenges facing disease management in this population. DESIGN:
      This study was a retrospective cohort analysis. SETTING AND PARTICIPANTS: The
      sample included 4156 nursing home residents in the SHELTER study. MEASUREMENT:
      All residents were assessed using the interRAI Long-Term Care Facility (LTCF)
      instrument. Use of angiotensin-converting enzyme inhibitor (ACEi) and/or
      angiotensin receptor blocker (ARB), beta-blocker (BB), antiaggregants (including
      acetylsalicylic acid [ASA]) and statins was analyzed. Based on the use of these
      medications, residents were classified into groups by medication use (as
      nonusers, 1-2 medications, or 3-4 medications). Generalized Estimation Equation
      modeling was used to explore predictors of medication use from items on the LTCF
      instrument as well as facility questionnaire. RESULTS: Of the 1050 residents with
      IHD, medication use was 77.7% overall, but only 16.9% were receiving 3 to 4
      medications. Use of antiaggregants was highest at 51.7% and variations in
      medication use were observed by country (highest in France and lowest in Italy).
      Functional disability was the strongest predictor of medication use, reducing the
      likelihood of any or optimal management. Severe cognitive impairment also reduced
      the likelihood of optimal management, and comorbidity generally increased the
      likelihood of medication use. Polypharmacy reduced the likelihood of use of 3 to
      4 medications for IHD. CONCLUSION: Optimal management of IHD in nursing home
      residents was low and varied by country. Individual characteristics seemed to
      predict IHD medication use, suggesting prescribing bias and an effect of
      population differences from clinical trial cohorts.

PMID- 24559642
TI  - Effects of a multicomponent home-based physical rehabilitation program on
      mobility recovery after hip fracture: a randomized controlled trial.
AB  - OBJECTIVE: To investigate whether a home-based rehabilitation program for
      community-dwelling older people with recent hip fracture is more effective than
      standard care in improving mobility recovery and reducing disability. DESIGN:
      Randomized, controlled, parallel-group trial. SETTING: Rehabilitation in
      participants' homes; measurements in university-based laboratory and local
      hospital. PARTICIPANTS: Clinical population of community-dwelling men and women
      (aged 60+) recovering from hip fracture. Participants were randomly assigned into
      control (n = 41) or intervention (n = 40) groups on average 42 +/- 23 days after
      discharge home. INTERVENTION: A yearlong multicomponent home-based rehabilitation
      aimed at promoting mobility recovery and physical functional capacity after hip
      fracture. The intervention included evaluation and modification of environmental
      hazards, guidance for safe walking, nonpharmacological pain management, a
      progressive home exercise program, physical activity counseling, and standard
      care. MEASUREMENTS: Measurements were outlined according to the tiers of the
      disablement process, with the ability to negotiate stairs as the main outcome.
      Prefracture ability to negotiate stairs was enquired at the hospital on average
      10 +/- 5 days after fracture. Subsequently, current perceived ability to
      negotiate stairs was reported immediately before the intervention (on average 9
      weeks after surgery) and 3, 6, and 12 months thereafter. Other measurements
      included leg extension power deficit (LEP), functional balance (Berg Balance
      Scale) and lower extremity performance (Short Physical Performance Battery).
      Effects of the intervention were analyzed with generalized estimation equations
      and longitudinal repeated measures mixture path models. RESULTS: The intervention
      reduced perceived difficulties in negotiating stairs (interaction, group * time P
      = .001) from prefracture to 12 months compared with the control condition. The
      mixture path model revealed that less difficulty in negotiating stairs at 6 and
      12 months correlated with better functional balance at 3 and 6 months in the
      intervention group but not controls (group difference P = .007 and P < .001,
      respectively). CONCLUSION: The individualized home-based rehabilitation program
      improved mobility recovery after hip fracture over standard care. To be
      efficacious in reducing or reversing disability after hip fracture,
      rehabilitation needs to be individualized, include many components, be
      progressive, and span a sufficiently long period. Current Controlled Trials
      (ISRCTN53680197).

PMID- 24559643
TI  - Trifluoperazine rescues human dopaminergic cells from wild-type alpha-synuclein
      induced toxicity.
AB  - Parkinson's disease (PD) is the most frequent neurodegenerative movement
      disorder. Presently, there is no causal therapy available to slow down or halt
      disease progression. The presynaptic protein alpha-synuclein aggregates to form
      intraneuronal Lewy bodies in PD. It is generally believed that intermediates on
      the way from monomers to the large aggregates would mediate neurotoxicity, but
      the precise species and mechanism responsible for neuronal death are
      controversially debated. To study alpha-synuclein-mediated toxicity, we developed
      a new model in which moderate overexpression of wild-type alpha-synuclein led to
      gradual death of human postmitotic dopaminergic neurons. In accordance with
      findings in postmortem PD brains, small oligomeric species occurred and the
      autophagic flux was impaired in our model. The phenothiazine neuroleptic
      trifluoperazine, an activator of macroautophagy, selectively reduced one
      particular alpha-synuclein species and rescued cells. Inversely, blocking of
      autophagy led to an accumulation of this oligomeric species and increased cell
      death. These data show that activation of autophagy is a promising approach to
      protect against alpha-synuclein pathology and likely acts by targeting one
      specific alpha-synuclein species. 

PMID- 24559644
TI  - MAPT IVS1+124 C>G modifies risk of LRRK2 G2385R for Parkinson's disease in
      Chinese individuals.
AB  - Variants of the MAPT gene have been suggested to be associated with Parkinson's
      disease (PD) and to modify the risk for leucine-rich repeat kinase 2 (LRRK2)
      Parkinsonism. However, this has not been confirmed in Asians with ethnicity
      specific variants of MAPT and LRRK2. In this study, Asian-specific LRRK2 p.G2385R
      variant and IVS1+124 C>G, a functional single-nucleotide polymorphism located in
      the MAPT promoter region, were genotyped in 561 Chinese PD patients and 556
      control subjects. Allelic and genotypic frequencies of the 2 variants were
      compared between cases and control subjects independently and in combination. As
      a result, the LRRK2 p.G2385R variant alone was associated with an increased risk
      for PD (Odds ratio, 1.86; 95% confidence intervals, 1.08-3.19; p = 0.014),
      whereas MAPT IVS1+124 C>G was not (p = 0.34). However, the coexistence of MAPT
      IVS1+124C>G significantly enhanced the LRRK2 G2385R-conferred risk for PD (Odds
      ratio, 2.30; 95% confidence intervals, 1.14-4.54; p = 0.012). These results
      provide further evidence supporting the interaction between MAPT and LRRK2 genes,
      which increases the susceptibility to PD in Chinese individuals.

PMID- 24559645
TI  - Reduced C9orf72 protein levels in frontal cortex of amyotrophic lateral sclerosis
      and frontotemporal degeneration brain with the C9ORF72 hexanucleotide repeat
      expansion.
AB  - An intronic G(4)C(2) hexanucleotide repeat expansion in C9ORF72 is a major cause
      of amyotrophic lateral sclerosis and frontotemporal lobar degeneration. Several
      mechanisms including RNA toxicity, repeat-associated non-AUG translation mediated
      dipeptide protein aggregates, and haploinsufficiency of C9orf72 have been
      implicated in the molecular pathogenesis of this disorder. The aims of this study
      were to compare the use of two different Southern blot probes for detection of
      repeat expansions in an amyotrophic lateral sclerosis and frontotemporal lobar
      degeneration pathological cohort and to determine the levels of C9orf72
      transcript variants and protein isoforms in patients versus control subjects. Our
      Southern blot studies identified smaller repeat expansions (250-1800 bp) that
      were only detectable with the flanking probe highlighting the potential for
      divergent results using different Southern blotting protocols that could
      complicate genotype-phenotype correlation studies. Further, we characterize a new
      C9orf72 antibody and show for the first time decreased C9orf72 protein levels in
      the frontal cortex from patients with a pathological hexanucleotide repeat
      expansion. These data suggest that a reduction in C9orf72 protein may be a
      consequence of the disease.

PMID- 24559647
TI  - Detecting gene mutations in Japanese Alzheimer's patients by semiconductor
      sequencing.
AB  - Alzheimer's disease (AD) is the most common form of dementia. To date, several
      genes have been identified as the cause of AD, including PSEN1, PSEN2, and APP.
      The association between APOE and late-onset AD has also been reported. We here
      used a bench top next-generation sequencer, which uses an integrated
      semiconductor device, detects hydrogen ions, and operates at a high-speed using
      nonoptical technology. We examined 45 Japanese AD patients with positive family
      histories, and 29 sporadic patients with early onset (<60-year-old). Causative
      mutations were detected in 5 patients in the familial group (11%). Three patients
      had a known heterozygous missense mutation in the PSEN1 gene (p.H163R). Two
      patients from 1 family had a novel heterozygous missense mutation in the PSEN1
      gene (p.F386L). In the early onset group, 1 patient carrying homozygous
      APOEepsilon4 had a novel heterozygous missense mutation in the PSEN2 gene
      (p.T421M). Approximately 43% patients were APOEepsilon4 positive in our study.
      This new sequencing technology is useful for detecting genetic variations in
      familial AD. 

PMID- 24559648
TI  - Neural stem and progenitor cells in the aged subependyma are activated by the
      young niche.
AB  - Previous studies have demonstrated an age related decline in the size of the
      neural stem cell (NSC) pool and a decrease in neural progenitor cell
      proliferation, however, the mechanisms underlying these changes are unclear. In
      contrast to previous reports, we report that the numbers of NSCs is unchanged in
      the old age subependyma and the apparent loss is because of reduced proliferative
      potential in the aged stem cell niche. Transplantation studies reveal that the
      proliferation kinetics and migratory behavior of neural precursor cells are
      dependent on the age of the host animal and independent of the age of the donor
      cells suggesting that young and old age neural precursors are not intrinsically
      different. Factors from the young stem cell niche rescue the numbers of NSC
      colonies derived from old age subependyma and enhance progenitor cell
      proliferation in vivo in old age mice. Finally, we report a loss of Wnt signaling
      in the old age stem cell niche that underlies the lack of expansion of the NSC
      pool after stroke.

PMID- 24559646
TI  - miR-126 contributes to Parkinson's disease by dysregulating the insulin-like
      growth factor/phosphoinositide 3-kinase signaling.
AB  - Dopamine (DA) neurons in sporadic Parkinson's disease (PD) display dysregulated
      gene expression networks and signaling pathways that are implicated in PD
      pathogenesis. Micro (mi)RNAs are regulators of gene expression, which could be
      involved in neurodegenerative diseases. We determined the miRNA profiles in laser
      microdissected DA neurons from postmortem sporadic PD patients' brains and age
      matched controls. DA neurons had a distinctive miRNA signature and a set of
      miRNAs was dysregulated in PD. Bioinformatics analysis provided evidence for
      correlations of miRNAs with signaling pathways relevant to PD, including an
      association of miR-126 with insulin/IGF-1/PI3K signaling. In DA neuronal cell
      systems, enhanced expression of miR-126 impaired IGF-1 signaling and increased
      vulnerability to the neurotoxin 6-OHDA by downregulating factors in IGF-1/PI3K
      signaling, including its targets p85beta, IRS-1, and SPRED1. Blocking of miR-126
      function increased IGF-1 trophism and neuroprotection to 6-OHDA. Our data imply
      that elevated levels of miR-126 may play a functional role in DA neurons and in
      PD pathogenesis by downregulating IGF-1/PI3K/AKT signaling and that its
      inhibition could be a mechanism of neuroprotection. 

PMID- 24559649
TI  - Maternal separation impairs long term-potentiation in CA1-CA3 synapses and
      hippocampal-dependent memory in old rats.
AB  - Exposure to chronic stress during the neonatal period is known to induce
      permanent long-term changes in the central nervous system and hipothalamic
      pituitary-adrenal axis reactivity that are associated with increased levels of
      depression, anxiety, and cognitive impairments. In rodents, a validated model of
      early life stress is the maternal separation (MS) paradigm, which has been shown
      to have long-term consequences for the pups that span to adulthood. We
      hypothesized that the early life stress-associated effects could be exacerbated
      with aging, because it is often accompanied by cognitive decline. Using a MS
      model in which rat pups were separated from their mothers for 3 hours daily,
      during postnatal days 2-14, we evaluated the long-term functional consequences to
      aged animals (70-week-old), by measuring synaptic plasticity and cognitive
      performance. The baseline behavioral deficits of aged control rats were further
      exacerbated in MS animals, indicating that early-life stress induces sustained
      changes in anxiety-like behavior and hippocampal-dependent memory that are
      maintained much later in life. We then investigated whether these differences are
      linked to impaired function of hippocampal neurons by recording hippocampal long
      term potentiation from Schaffer collaterals/CA1 synapses. The magnitude of the
      hippocampal long-term potentiation induced by high-frequency stimulation was
      significantly lower in aged MS animals than in age-matched controls. These
      results substantiate the hypothesis that the neuronal and endocrine alterations
      induced by early-life stress are long lasting, and are able to exacerbate the
      mild age-associated deficits. 

PMID- 24559650
TI  - Health related quality of life in head and neck cancer treated with radiation
      therapy with or without chemotherapy: a systematic review.
AB  - Health-related quality of life (HRQoL) is a subjective measure of patients'
      experience of disease and treatment. We systematically reviewed the literature to
      identify high quality manuscripts reporting HRQoL outcomes in adults with
      squamous cell carcinoma of the head and neck (HNSCC) treated with an organ
      sparing curative regimen of radiation therapy with or without chemotherapy.
      Assessments were performed independently by two reviewers; a third reviewer
      resolved disputes. High quality reports were reviewed in detail to identify
      trends in HRQoL outcomes. MEDLINE and EMBASE searching yielded 276 distinct
      reports, plus 24 added via hand search. Of these, 53 met eligibility criteria and
      18 were deemed high quality reports on the basis of a quality assessment tool.
      HRQoL declines after treatment but recovers to baseline levels, generally within
      12months. However, xerostomia-related HRQoL deficits may remain long-term.
      Combined chemoradiotherapy showed a trend toward worse HRQoL compared with RT
      alone. Intensity modulated radiotherapy (IMRT) yields better HRQoL compared with
      conventional or three-dimensional conformal radiotherapy. Baseline HRQoL may
      independently predict local-regional control and overall survival. Future
      research should incorporate HRQoL into phase III trials. However, adequate effort
      and journal space must be afforded to the HRQoL results of these studies to
      ensure proper reporting methods are followed, allowing clinicians to incorporate
      HRQoL into patient counseling and clinical decision making. 

PMID- 24559651
TI  - Elevating the quality of disability and rehabilitation research: mandatory use of
      the reporting guidelines.

PMID- 24559654
TI  - Vehicle routing for the eco-efficient collection of household plastic waste.
AB  - Plastic waste is a special category of municipal solid waste. Plastic waste
      collection is featured with various alternatives of collection methods
      (curbside/drop-off) and separation methods (source-/post-separation). In the
      Netherlands, the collection routes of plastic waste are the same as those of
      other waste, although plastic is different than other waste in terms of volume to
      weight ratio. This paper aims for redesigning the collection routes and compares
      the collection options of plastic waste using eco-efficiency as performance
      indicator. Eco-efficiency concerns the trade-off between environmental impacts,
      social issues and costs. The collection problem is modeled as a vehicle routing
      problem. A tabu search heuristic is used to improve the routes. Collection
      alternatives are compared by a scenario study approach. Real distances between
      locations are calculated with MapPoint. The scenario study is conducted based on
      real case data of the Dutch municipality Wageningen. Scenarios are designed
      according to the collection alternatives with different assumptions in collection
      method, vehicle type, collection frequency and collection points, etc. Results
      show that the current collection routes can be improved in terms of eco
      efficiency performance by using our method. The source-separation drop-off
      collection scenario has the best performance for plastic collection assuming
      householders take the waste to the drop-off points in a sustainable manner. The
      model also shows to be an efficient decision support tool to investigate the
      impacts of future changes such as alternative vehicle type and different response
      rates. 

PMID- 24559652
TI  - Ca2+-dependent K+ channels in exocrine salivary glands.
AB  - In the last 15 years, remarkable progress has been realized in identifying the
      genes that encode the ion-transporting proteins involved in exocrine gland
      function, including salivary glands. Among these proteins, Ca(2+)-dependent K(+)
      channels take part in key functions including membrane potential regulation,
      fluid movement and K(+) secretion in exocrine glands. Two K(+) channels have been
      identified in exocrine salivary glands: (1) a Ca(2+)-activated K(+) channel of
      intermediate single channel conductance encoded by the KCNN4 gene, and (2) a
      voltage- and Ca(2+)-dependent K(+) channel of large single channel conductance
      encoded by the KCNMA1 gene. This review focuses on the physiological roles of
      Ca(2+)-dependent K(+) channels in exocrine salivary glands. We also discuss
      interesting recent findings on the regulation of Ca(2+)-dependent K(+) channels
      by protein-protein interactions that may significantly impact exocrine gland
      physiology. 

PMID- 24559655
TI  - Overexpression of Shati/Nat8l, an N-acetyltransferase, in the nucleus accumbens
      attenuates the response to methamphetamine via activation of group II mGluRs in
      mice.
AB  - A novel N-acetyltransferase, Shati/Nat8l, was identified in the nucleus accumbens
      (NAc) of mice with methamphetamine (METH) treatment. Previously we reported that
      suppression of Shati/Nat8l enhanced METH-induced behavioral alterations via
      dopaminergic neuronal regulation. However, the physiological mechanisms of
      Shati/Nat8l on the dopaminergic system in the brain are unclear. In this study,
      we injected adeno-associated virus (AAV) vector containing Shati/Nat8l into the
      NAc or dorsal striatum (dS) of mice, to increase Shati/Nat8l expression.
      Overexpression of Shati/Nat8l in the NAc, but not in the dS, attenuated METH
      induced hyperlocomotion, locomotor sensitization, and conditioned place
      preference in mice. Moreover, the Shati/Nat8l overexpression in the NAc
      attenuated the elevation of extracellular dopamine levels induced by METH in in
      vivo microdialysis experiments. These behavioral and neurochemical alterations
      due to Shati/Nat8l overexpression in the NAc were inhibited by treatment with
      selective group II metabotropic glutamate receptor type 2 and 3 (mGluR2/3)
      antagonist LY341495. In the AAV vector-injected NAc, the tissue contents of both
      N-acetylaspartate and N-acetylaspartylglutamate (NAAG), endogenous mGluR3
      agonist, were elevated. The injection of peptidase inhibitor of NAAG or the
      perfusion of NAAG itself reduced the basal levels of extracellular dopamine in
      the NAc of naive mice. These results indicate that Shati/Nat8l in the NAc, but
      not in the dS, plays an important suppressive role in the behavioral responses to
      METH by controlling the dopaminergic system via activation of group II mGluRs. 

PMID- 24559656
TI  - Behcet's disease presenting as a peripheral vestibulopathy.
AB  - Prolonged acute spontaneous vertigo can be secondary to acute vestibular neuritis
      or posterior circulation ischaemia. We present a 66-year-old man who first
      developed an acute vestibular syndrome with profound unilateral hearing loss 34
      years ago. First treated as vestibular neuritis, he subsequently developed
      manifestations of Behcet's disease, including mouth ulcers, genital ulcers and
      erythema nodosum over a period of 10 years. Subsequently, sudden sensorineural
      hearing loss affecting his only hearing ear responded to immunomodulation,
      confirming an autoimmune cause for the audiovestibular symptoms. This report
      serves as a reminder that vestibular neuritis seldom causes hearing loss;
      ischaemic, infective and autoimmune causes should be sought when an acute
      vestibular syndrome is accompanied by hearing impairment.

PMID- 24559658
TI  - Birth defects and assisted reproductive technologies.
AB  - Assisted reproductive technologies (ART) using in-vitro fertilization (IVF)
      account for ~1% of births in the USA and as much as 3-4% in Europe or Australia.
      Initially studies involved infants prospectively examined in an early cohort of
      US births, with salutary results. Later studies began to show the frequency of
      birth defects to be increased. In meta-analysis, odds ratio was >1.0, with the
      95% confidence limit not extending to <1.0. Although ART are associated with a
      30% increase in birth defects; subfertile couples achieving pregnancy without ART
      show a 20% increase. It thus appears that the increase in birth defects is due
      less, if at all, to ART protocols per se than to the biological perturbations
      that generated the infertility that necessitated ART to achieve pregnancy. There
      is consensus that traditional IVF and intracytoplasmic sperm injection (ICSI)/IVF
      show the same overall risk notwithstanding increased sex chromosome abnormalities
      in both procedures and increased hypospadias in ICSI. No other organ system seems
      disproportionately affected. There is no additive risk in ART twins compared with
      non-ART twins, nor in embryos having been cryopreserved. The increased risk
      observed had not appeared to dissuade couples from attempting to have their own
      children. 

PMID- 24559657
TI  - Narcolepsy, 2009 A(H1N1) pandemic influenza, and pandemic influenza vaccinations:
      what is known and unknown about the neurological disorder, the role for
      autoimmunity, and vaccine adjuvants.
AB  - The vaccine safety surveillance system effectively detected a very rare adverse
      event, narcolepsy, in subjects receiving AS03-adjuvanted A(H1N1) pandemic vaccine
      made using the European inactivation/purification protocol. The reports of
      increased cases of narcolepsy in non-vaccinated subjects infected with wild
      A(H1N1) pandemic influenza virus suggest a role for the viral antigen(s) in
      disease development. However, additional investigations are needed to better
      understand what factor(s) in wild influenza infection trigger(s) narcolepsy in
      susceptible hosts. An estimated 31 million doses of European AS03-adjuvanted
      A(H1N1) pandemic vaccine were used in more than 47 countries. The Canadian AS03
      adjuvanted A(H1N1) pandemic vaccine was used with high coverage in Canada where
      an estimated 12 million doses were administered. As no similar narcolepsy
      association has been reported to date with the AS03-adjuvanted A(H1N1) pandemic
      vaccine made using the Canadian inactivation/purification protocol, this suggests
      that the AS03 adjuvant alone may not be responsible for the narcolepsy
      association. To date, no narcolepsy association has been reported with the
      MF59(r)-adjuvanted A(H1N1) pandemic vaccine. This review article provides a brief
      background on narcolepsy, outlines the different types of vaccine preparations
      including the ones for influenza, reviews the accumulated evidence for the safety
      of adjuvants, and explores the association between autoimmune diseases and
      natural infections. It concludes by assimilating the historical observations and
      recent clinical studies to formulate a feasible hypothesis on why vaccine
      associated narcolepsy may not be solely linked to the AS03 adjuvant but more
      likely be linked to how the specific influenza antigen component of the European
      AS03-adjuvanted pandemic vaccine was prepared. Careful and long-term
      epidemiological studies of subjects who developed narcolepsy in association with
      AS03-adjuvanted A(H1N1) pandemic vaccine prepared with the European
      inactivation/purification protocol are needed. 

PMID- 24559660
TI  - Molecular epidemiology of Salmonella enterica serovar Kottbus isolated in Germany
      from humans, food and animals.
AB  - Salmonella enterica serovar Kottbus has been continuously isolated from poultry
      and poultry meat, especially from turkey. We investigated by comparative
      molecular typing 95 S. Kottbus isolates obtained in Germany between 2000 and 2011
      from poultry/poultry meat, pig/pork, cattle, reptiles, the environment as well as
      from human cases to identify potential infection sources for humans, especially
      the role of poultry and poultry products as vehicle in transmission of S. Kottbus
      isolates to humans. Multilocus sequence typing analysis detected three main
      genetic lineages. Most human isolates belonged to lineage 1 represented by
      sequence types ST212 and ST808. Part of the isolates isolated from cattle and
      pork were also linked to this lineage. Nevertheless, human isolates and
      especially isolates from poultry/poultry meat, and with less extend from other
      livestock, grouped in lineage 2 represented by ST582. Four additional isolates
      from reptiles and humans belonging to ST1669 represented the third lineage. The
      three lineages were also reflected by pulsed-field gel electrophoresis typing
      data and DNA microarray analysis of 102 pathogenicity genes. Antimicrobial
      resistance especially to nalidixic acid and ciprofloxacin was predominantly
      observed in isolates assigned to lineage 2, which contains predominantly
      resistant isolates compared to lineage 1 and 3. Sequencing of the quinolone
      resistance-determining region of gyrA revealed a point mutation in codon 83 or 87
      responsible for nalidixic acid resistance and MIC values for ciprofloxacin
      between 0.125 and 0.25mg/l. Overall, this study showed that in Germany a specific
      S. Kottbus lineage (ST582), which is well-established in poultry, can be
      transmitted to humans by poultry meat and, consequently, poses a risk for human
      health.

PMID- 24559659
TI  - High-field proton magnetic resonance spectroscopy reveals metabolic effects of
      normal brain aging.
AB  - Altered brain metabolism is likely to be an important contributor to normal
      cognitive decline and brain pathology in elderly individuals. To characterize the
      metabolic changes associated with normal brain aging, we used high-field proton
      magnetic resonance spectroscopy in vivo to quantify 20 neurochemicals in the
      hippocampus and sensorimotor cortex of young adult and aged rats. We found
      significant differences in the neurochemical profile of the aged brain when
      compared with younger adults, including lower aspartate, ascorbate, glutamate,
      and macromolecules, and higher glucose, myo-inositol, N-acetylaspartylglutamate,
      total choline, and glutamine. These neurochemical biomarkers point to specific
      cellular mechanisms that are altered in brain aging, such as bioenergetics,
      oxidative stress, inflammation, cell membrane turnover, and endogenous
      neuroprotection. Proton magnetic resonance spectroscopy may be a valuable
      translational approach for studying mechanisms of brain aging and pathology, and
      for investigating treatments to preserve or enhance cognitive function in aging.

PMID- 24559661
TI  - Triple stimulation technique findings in vascular Parkinsonism and Parkinson's
      disease.
AB  - OBJECTIVE: One of the predominant clinical features that differentiates vascular
      Parkinsonism (VP) from Parkinson's disease (PD) is the pyramidal sign. The triple
      stimulation technique (TST) is one of the most sensitive methods for comparing
      upper motor neuron involvement in patients with VP and PD. This study aimed to
      evaluate the usefulness of the TST as a diagnostic tool for VP. METHODS: Thirteen
      VP patients, 18 PD patients and 10 age-matched healthy controls were enrolled in
      this study. We obtained basic participant demographic information and
      transcranial magnetic stimulation (TMS) parameters, including the TST amplitude
      ratio, from all participants. We compared the TMS parameters among the VP, PD and
      control groups. RESULTS: The TST amplitude ratio was significantly lower in the
      VP group than in the PD and control groups (71.59 +/- 11.86 vs. 96.42 +/- 5.11
      and 97.70 +/- 3.82, respectively; p<0.01). The TST amplitude ratio was positively
      correlated with scores obtained on the United Parkinson's Disease Rating Scale
      III, which reflects motor function. CONCLUSIONS: The TST is an effective and easy
      technique that offers improved diagnostic sensitivity in patients with VP by
      assessing upper motor neuron involvement. The TST may also represent a useful
      monitoring tool for evaluating disease progression. SIGNIFICANCE: This study is
      the first to assess pyramidal involvement in patients with VP using the collision
      technique.

PMID- 24559662
TI  - Event-related potential measures of gap detection threshold during natural sleep.
AB  - OBJECTIVE: The minimum time interval between two stimuli that can be reliably
      detected is called the gap detection threshold. The present study examines
      whether an unconscious state, natural sleep affects the gap detection threshold.
      METHODS: Event-related potentials were recorded in 10 young adults while awake
      and during all-night sleep to provide an objective estimate of this threshold.
      These subjects were presented with 2, 4, 8 or 16ms gaps occurring in 1.5 duration
      white noise. RESULTS: During wakefulness, a significant N1 was elicited for the 8
      and 16ms gaps. N1 was difficult to observe during stage N2 sleep, even for the
      longest gap. A large P2 was however elicited and was significant for the 8 and
      16ms gaps. Also, a later, very large N350 was elicited by the 16ms gap. An N1 and
      P2 was significant only for the 16ms gap during REM sleep. SIGNIFICANCE: ERPs to
      gaps occurring in noise segments can therefore be successfully elicited during
      natural sleep. The gap detection threshold is similar in the waking and sleeping
      states.

PMID- 24559663
TI  - [Reply to: Prediction of risk in the elderly patient with acute coronary
      syndrome].

PMID- 24559664
TI  - [An analysis of the relationship between the attitudes towards old age and
      ageing, and well-being indicators in a sample of old people].
AB  - INTRODUCTION: In the last stage of their life cycle, old people can enjoy a
      satisfactory ageing thanks to the improvement of their quality of life. The
      present study analyses the links between 2 relevant variables at this life stage:
      the attitudes of the elderly towards their own ageing and their own physical and
      psychological state of well-being. MATERIAL AND METHOD: The sample consisted of
      people over the age of 50 without cognitive impairment and with functional
      independence in their daily life (N = 117). The analyses include descriptive
      statistical data, gender differences and correlation matrices. RESULTS: The
      results of this study indicate that the positive attitude factors towards the old
      age and the ageing are related to the physical and psychological well-being,
      whilst negative attitude factors lead to a general state of malaise. The
      population sample showed a relative satisfaction with their life, as well as a
      low physical and psychological malaise. CONCLUSIONS: The results of this study
      reflect the significance of positive attitudes in the well-being of old people,
      with a direct impact on their quality of life.

PMID- 24559665
TI  - Good housekeeping.
AB  - In this issue of Neuron, Tani et al. (2014) revisit a disputed issue where
      biochemical and physiological data have provided conflicting results. Using a
      novel stimulation protocol, the authors isolate the contribution of the glutamate
      glutamine cycle to excitatory synaptic transmission.

PMID- 24559666
TI  - Retrograde signaling causes excitement.
AB  - Retrograde signaling is a powerful tool to shape synaptic transmission, typically
      inducing inhibition of transmitter release. A new study published in this issue
      of Neuron by Carta et al. (2014) now provides strong support for arachidonic acid
      as a potentiating retrograde messenger.

PMID- 24559667
TI  - A Drosophila circuit feels the (sleep) pressure.
AB  - How sleep is homeostatically regulated remains a mystery. In this issue of
      Neuron, Donlea et al. (2014) provide evidence in Drosophila that a set of sleep
      inducing neurons require Crossveinless-c, a specific Rho-GTPase-activating
      protein (Rho-Gap), to alter their membrane excitability in response to sleep
      deprivation.

PMID- 24559668
TI  - All roads lead to neuroscience: the 2013 Nobel Prize in Physiology or Medicine.
AB  - Numerous metaphors have been employed to describe the achievements of the 2013
      Nobel Laureates in Physiology or Medicine, James E. Rothman, Randy W. Schekman,
      and Thomas C. Sudhof, who were honored for "their discoveries of machinery
      regulating vesicle traffic, a major transport system in our cells." Most of these
      metaphors referred to the mundane issue of business logistics, and there is
      probably no other cell type in which the logistics problem is more pressing than
      in neurons. 

PMID- 24559669
TI  - Gliotransmitters travel in time and space.
AB  - The identification of the presence of active signaling between astrocytes and
      neurons in a process termed gliotransmission has caused a paradigm shift in our
      thinking about brain function. However, we are still in the early days of the
      conceptualization of how astrocytes influence synapses, neurons, networks, and
      ultimately behavior. In this Perspective, our goal is to identify emerging
      principles governing gliotransmission and consider the specific properties of
      this process that endow the astrocyte with unique functions in brain signal
      integration. We develop and present hypotheses aimed at reconciling confounding
      reports and define open questions to provide a conceptual framework for future
      studies. We propose that astrocytes mainly signal through high-affinity slowly
      desensitizing receptors to modulate neurons and perform integration in
      spatiotemporal domains complementary to those of neurons. 

PMID- 24559671
TI  - A systematic nomenclature for the insect brain.
AB  - Despite the importance of the insect nervous system for functional and
      developmental neuroscience, descriptions of insect brains have suffered from a
      lack of uniform nomenclature. Ambiguous definitions of brain regions and fiber
      bundles have contributed to the variation of names used to describe the same
      structure. The lack of clearly determined neuropil boundaries has made it
      difficult to document precise locations of neuronal projections for connectomics
      study. To address such issues, a consortium of neurobiologists studying arthropod
      brains, the Insect Brain Name Working Group, has established the present
      hierarchical nomenclature system, using the brain of Drosophila melanogaster as
      the reference framework, while taking the brains of other taxa into careful
      consideration for maximum consistency and expandability. The following summarizes
      the consortium's nomenclature system and highlights examples of existing
      ambiguities and remedies for them. This nomenclature is intended to serve as a
      standard of reference for the study of the brain of Drosophila and other insects.

PMID- 24559672
TI  - Cas adaptor proteins organize the retinal ganglion cell layer downstream of
      integrin signaling.
AB  - Stratification of retinal neuronal cell bodies and lamination of their processes
      provide a scaffold upon which neural circuits can be built. However, the
      molecular mechanisms that direct retinal ganglion cells (RGCs) to resolve into a
      single-cell retinal ganglion cell layer (GCL) are not well understood. The
      extracellular matrix protein laminin conveys spatial information that instructs
      the migration, process outgrowth, and reorganization of GCL cells. Here, we show
      that the beta1-Integrin laminin receptor is required for RGC positioning and
      reorganization into a single-cell GCL layer. beta1-Integrin signaling within
      migrating GCL cells requires Cas signaling-adaptor proteins, and in the absence
      of beta1-Integrin or Cas function retinal neurons form ectopic cell clusters
      beyond the inner-limiting membrane (ILM), phenocopying laminin mutants. These
      data reveal an essential role for Cas adaptor proteins in beta1-Integrin-mediated
      signaling events critical for the formation of the single-cell GCL in the
      mammalian retina.

PMID- 24559670
TI  - ApoE and Abeta in Alzheimer's disease: accidental encounters or partners?
AB  - Among the three human apolipoprotein E (apoE) isoforms, apoE4 increases the risk
      of Alzheimer's disease (AD). While transporting cholesterol is a primary
      function, apoE also regulates amyloid-beta (Abeta) metabolism, aggregation, and
      deposition. Although earlier work suggests that different affinities of apoE
      isoforms to Abeta might account for their effects on Abeta clearance, recent
      studies indicate that apoE also competes with Abeta for cellular uptake through
      apoE receptors. Thus, several factors probably determine the variable effects
      apoE has on Abeta. In this Review, we examine biochemical, structural, and
      functional studies and propose testable models that address the complex
      mechanisms underlying apoE-Abeta interaction and how apoE4 may increase AD risk
      and also serve as a target pathway for therapy. 

PMID- 24559673
TI  - Restoring visual function to blind mice with a photoswitch that exploits
      electrophysiological remodeling of retinal ganglion cells.
AB  - Retinitis pigmentosa (RP) and age-related macular degeneration (AMD) are blinding
      diseases caused by the degeneration of rods and cones, leaving the remainder of
      the visual system unable to respond to light. Here, we report a chemical
      photoswitch named DENAQ that restores retinal responses to white light of
      intensity similar to ordinary daylight. A single intraocular injection of DENAQ
      photosensitizes the blind retina for days, restoring electrophysiological and
      behavioral responses with no toxicity. Experiments on mouse strains with
      functional, nonfunctional, or degenerated rods and cones show that DENAQ is
      effective only in retinas with degenerated photoreceptors. DENAQ confers light
      sensitivity on a hyperpolarization-activated inward current that is enhanced in
      degenerated retina, enabling optical control of retinal ganglion cell firing. The
      acceptable light sensitivity, favorable spectral sensitivity, and selective
      targeting to diseased tissue make DENAQ a prime drug candidate for vision
      restoration in patients with end-stage RP and AMD.

PMID- 24559674
TI  - Pioneering axons regulate neuronal polarization in the developing cerebral
      cortex.
AB  - The polarization of neurons, which mainly includes the differentiation of axons
      and dendrites, is regulated by cell-autonomous and non-cell-autonomous factors.
      In the developing central nervous system, neuronal development occurs in a
      heterogeneous environment that also comprises extracellular matrices, radial
      glial cells, and neurons. Although many cell-autonomous factors that affect
      neuronal polarization have been identified, the microenvironmental cues involved
      in neuronal polarization remain largely unknown. Here, we show that neuronal
      polarization occurs in a microenvironment in the lower intermediate zone, where
      the cell adhesion molecule transient axonal glycoprotein-1 (TAG-1) is expressed
      in cortical efferent axons. The immature neurites of multipolar cells closely
      contact TAG-1-positive axons and generate axons. Inhibition of TAG-1-mediated
      cell-to-cell interaction or its downstream kinase Lyn impairs neuronal
      polarization. These results show that the TAG-1-mediated cell-to-cell interaction
      between the unpolarized multipolar cells and the pioneering axons regulates the
      polarization of multipolar cells partly through Lyn kinase and Rac1.

PMID- 24559675
TI  - Silencing of odorant receptor genes by G protein betagamma signaling ensures the
      expression of one odorant receptor per olfactory sensory neuron.
AB  - Olfactory sensory neurons express just one out of a possible ~ 1,000 odorant
      receptor genes, reflecting an exquisite mode of gene regulation. In one model,
      once an odorant receptor is chosen for expression, other receptor genes are
      suppressed by a negative feedback mechanism, ensuring a stable functional
      identity of the sensory neuron for the lifetime of the cell. The signal
      transduction mechanism subserving odorant receptor gene silencing remains
      obscure, however. Here, we demonstrate in the zebrafish that odorant receptor
      gene silencing is dependent on receptor activity. Moreover, we show that
      signaling through G protein betagamma subunits is both necessary and sufficient
      to suppress the expression of odorant receptor genes and likely acts through
      histone methylation to maintain the silenced odorant receptor genes in
      transcriptionally inactive heterochromatin. These results link receptor activity
      with the epigenetic mechanisms responsible for ensuring the expression of one
      odorant receptor per olfactory sensory neuron.

PMID- 24559676
TI  - Neuronal machinery of sleep homeostasis in Drosophila.
AB  - Sleep is under homeostatic control, but the mechanisms that sense sleep need and
      correct sleep deficits remain unknown. Here, we report that sleep-promoting
      neurons with projections to the dorsal fan-shaped body (FB) form the output arm
      of Drosophila's sleep homeostat. Homeostatic sleep control requires the Rho
      GTPase-activating protein encoded by the crossveinless-c (cv-c) gene in order to
      transduce sleep pressure into increased electrical excitability of dorsal FB
      neurons. cv-c mutants exhibit decreased sleep time, diminished sleep rebound, and
      memory deficits comparable to those after sleep loss. Targeted ablation and
      rescue of Cv-c in sleep-control neurons of the dorsal FB impair and restore,
      respectively, normal sleep patterns. Sleep deprivation increases the excitability
      of dorsal FB neurons, but this homeostatic adjustment is disrupted in short
      sleeping cv-c mutants. Sleep pressure thus shifts the input-output function of
      sleep-promoting neurons toward heightened activity by modulating ion channel
      function in a mechanism dependent on Cv-c. 

PMID- 24559677
TI  - A local glutamate-glutamine cycle sustains synaptic excitatory transmitter
      release.
AB  - Biochemical studies suggest that excitatory neurons are metabolically coupled
      with astrocytes to generate glutamate for release. However, the extent to which
      glutamatergic neurotransmission depends on this process remains controversial
      because direct electrophysiological evidence is lacking. The distance between
      cell bodies and axon terminals predicts that glutamine-glutamate cycle is
      synaptically localized. Hence, we investigated isolated nerve terminals in brain
      slices by transecting hippocampal Schaffer collaterals and cortical layer I
      axons. Stimulating with alternating periods of high frequency (20 Hz) and rest
      (0.2 Hz), we identified an activity-dependent reduction in synaptic efficacy that
      correlated with reduced glutamate release. This was enhanced by inhibition of
      astrocytic glutamine synthetase and reversed or prevented by exogenous glutamine.
      Importantly, this activity dependence was also revealed with an in-vivo-derived
      natural stimulus both at network and cellular levels. These data provide direct
      electrophysiological evidence that an astrocyte-dependent glutamate-glutamine
      cycle is required to maintain active neurotransmission at excitatory terminals.

PMID- 24559678
TI  - Dopamine neurons control striatal cholinergic neurons via regionally
      heterogeneous dopamine and glutamate signaling.
AB  - Midbrain dopamine neurons fire in bursts conveying salient information. Bursts
      are associated with pauses in tonic firing of striatal cholinergic interneurons.
      Although the reciprocal balance of dopamine and acetylcholine in the striatum is
      well known, how dopamine neurons control cholinergic neurons has not been
      elucidated. Here, we show that dopamine neurons make direct fast dopaminergic and
      glutamatergic connections with cholinergic interneurons, with regional
      heterogeneity. Dopamine neurons drive a burst-pause firing sequence in
      cholinergic interneurons in the medial shell of the nucleus accumbens, mixed
      actions in the accumbens core, and a pause in the dorsal striatum. This
      heterogeneity is due mainly to regional variation in dopamine-neuron glutamate
      cotransmission. A single dose of amphetamine attenuates dopamine neuron
      connections to cholinergic interneurons with dose-dependent regional specificity.
      Overall, the present data indicate that dopamine neurons control striatal circuit
      function via discrete, plastic connections with cholinergic interneurons. 

PMID- 24559679
TI  - Structured connectivity in cerebellar inhibitory networks.
AB  - Defining the rules governing synaptic connectivity is key to formulating theories
      of neural circuit function. Interneurons can be connected by both electrical and
      chemical synapses, but the organization and interaction of these two
      complementary microcircuits is unknown. By recording from multiple molecular
      layer interneurons in the cerebellar cortex, we reveal specific, nonrandom
      connectivity patterns in both GABAergic chemical and electrical interneuron
      networks. Both networks contain clustered motifs and show specific overlap
      between them. Chemical connections exhibit a preference for transitive patterns,
      such as feedforward triplet motifs. This structured connectivity is supported by
      a characteristic spatial organization: transitivity of chemical connectivity is
      directed vertically in the sagittal plane, and electrical synapses appear
      strictly confined to the sagittal plane. The specific, highly structured
      connectivity rules suggest that these motifs are essential for the function of
      the cerebellar network. 

PMID- 24559680
TI  - Corticostriatal output gating during selection from working memory.
AB  - Convergent evidence suggests that corticostriatal interactions act as a gate to
      select the input to working memory (WM). However, not all information in WM is
      relevant for behavior simultaneously. For this reason, a second "output gate"
      might advantageously govern which contents of WM influence behavior. Here, we
      test whether frontostriatal circuits previously implicated in input gating also
      support output gating during selection from WM. fMRI of a hierarchical rule task
      with dissociable input and output gating demands demonstrated greater lateral
      prefrontal cortex (PFC) recruitment and frontostriatal connectivity during output
      gating. Moreover, PFC and striatum correlated with distinct behavioral profiles.
      Whereas PFC recruitment correlated with mean efficiency of selection from WM,
      striatal recruitment and frontostriatal interactions correlated with its
      reliability, as though such dynamics stochastically gate WM's output. These
      results support the output gating hypothesis, suggesting that contextual
      representations in PFC influence striatum to select which information in WM
      drives responding.

PMID- 24559682
TI  - SnapShot: local protein translation in dendrites.

PMID- 24559681
TI  - Statistical wiring of thalamic receptive fields optimizes spatial sampling of the
      retinal image.
AB  - It is widely assumed that mosaics of retinal ganglion cells establish the optimal
      representation of visual space. However, relay cells in the visual thalamus often
      receive convergent input from several retinal afferents and, in cat, outnumber
      ganglion cells. To explore how the thalamus transforms the retinal image, we
      built a model of the retinothalamic circuit using experimental data and simple
      wiring rules. The model shows how the thalamus might form a resampled map of
      visual space with the potential to facilitate detection of stimulus position in
      the presence of sensor noise. Bayesian decoding conducted with the model provides
      support for this scenario. Despite its benefits, however, resampling introduces
      image blur, thus impairing edge perception. Whole-cell recordings obtained in
      vivo suggest that this problem is mitigated by arrangements of excitation and
      inhibition within the receptive field that effectively boost contrast borders,
      much like strategies used in digital image processing.

PMID- 24559683
TI  - SPIDER (r) sleeve gastrectomy--a new concept in single-trocar bariatric surgery:
      initial experience and technical details.
AB  - INTRODUCTION: Single port instrument delivery extended reach (SPIDER((r)))
      surgical system is a revolutionary surgical platform that allows triangulation of
      the surgical instruments while eliminating the crossing of instruments, the
      problematic characteristic of single access laparoscopic surgery. METHODS: The
      purpose of this study was to analyze our initial experience with SPIDER((r))
      sleeve gastrectomy and to present the technical details of this new minimally
      invasive approach, performed in ten patients at the La Casamance Private Hospital
      between November 2012 and April 2013. All patients were reviewed at scheduled
      post-operative consultations at 1, 3 and 6 months. In addition to clinical
      examination, the post-operative consultation at one month also included a
      satisfaction survey using the Moorehead-Ardelt questionnaire. RESULTS: An initial
      series of ten sleeve gastrectomies were performed in female patients with a mean
      age of 41.5 years (range: 2-52). The mean BMI was 40.11 (range: 37.25-44.3). The
      intervention was performed through a single trocar in all patients with no
      "conversion" to classic laparoscopy or open surgery. The mean operative time was
      61 +/- 15.22 minutes (SD=standard deviation) (range: 43-96 min). The mean BMI at
      one month was 35.5 (SD:+/- 3.58, SEM: +/- 1.13) (SEM=standard error of mean) with
      an average percentage of excess weight loss (%EWL) of 32.9% (SD:+/- 8.56%, SEM:+/
      2.71%). The mean BMI at three months was 32.4 (SD: +/- 2.78, SEM: +/- 0.88) with
      an average %EWL of 52.7% (SD: +/- 8.64%, SEM: +/- 2.73%). The mean BMI at six
      months was 29.9 (SD:+/- 2.60, SEM: +/- 0.98) with a mean %EWL of 68.8% (SD: +/-
      8.38%, SEM:+/- 3.17%). Complete remission of co-morbid conditions was observed in
      four patients, improvement in three others, and no change in a single patient.
      The mean duration of hospitalization was 3.1 days. The mean follow-up period was
      161 days (SD:+/- 57.4 days, range: 90-243 days). There was no mortality and no
      intra-operative and post-operative complications were noted. CONCLUSIONS: The
      SPIDER((r)) surgical platform seems to be a usable and effective method for
      performance of minimally invasive single-access sleeve gastrectomy, offering an
      easy and efficient operative procedure compared to other single-port systems.
      Prospective long-term studies are recommended before this approach can be
      validated to be of comparable efficiency to conventional multi-port laparoscopic
      surgery.

PMID- 24559684
TI  - Comparing the effects of single shot sciatic nerve block versus posterior capsule
      local anesthetic infiltration on analgesia and functional outcome after total
      knee arthroplasty: a prospective, randomized, double-blinded, controlled trial.
AB  - Peripheral nerve blocks appear to provide effective analgesia for patients
      undergoing total knee arthroplasty. Although the literature supports the use of
      femoral nerve block, addition of sciatic nerve block is controversial. In this
      study we investigated the value of sciatic nerve block and an alternative
      technique of posterior capsule local anesthetic infiltration analgesia. 100
      patients were prospectively randomized into three groups. Group 1: sciatic nerve
      block; Group 2: posterior local anesthetic infiltration; Group 3: control. All
      patients received a femoral nerve block and spinal anesthesia. There were no
      differences in pain scores between groups. Sciatic nerve block provided a brief
      clinically insignificant opioid sparing effect. We conclude that sciatic nerve
      block and posterior local anesthetic infiltration do not provide significant
      analgesic benefits. 

PMID- 24559685
TI  - Downregulation of HOXA1 gene affects small cell lung cancer cell survival and
      chemoresistance under the regulation of miR-100.
AB  - Chemoresistance is often developed in small cell lung cancer (SCLC) patients and
      leads to poor prognosis. Hox genes, a highly conserved family, play a crucial
      role in apoptosis, receptor signalling and differentiation. MicroRNAs (miRNAs)
      have also been shown to play a crucial role in these biological processes by
      regulating the target genes. Several studies reported that both Hox genes and
      miRNAs are involved in chemoresistance. The aim of our study is to characterise
      the clinical significance and functional roles of HOXA1 in SCLC. Expression of
      HOXA1 was examined in 63 cases of SCLC tissues and 29 cases of blood by
      immunohistochemistry and quantitative reverse transcription-polymerase chain
      reaction (qRT-PCR) methods. Multivariate analysis confirmed the prognostic
      significance of HOXA1 in SCLC patients. Restoration of HOXA1 expression was
      carried out in SCLC multidrug resistant cell line H69AR and its parental cell
      line H69 to assess its influence on chemoresistance. Luciferase reporter assay
      was used to assess HOXA1 as a target of miR-100. The results showed that HOXA1
      was expressed in 46% (29/63) of SCLC. Low HOXA1 expression was associated with
      the poor prognosis of SCLC (P<0.05 by the Fisher's Exact Test) and the shorter
      survival rate (P<0.001 by the Kaplan-Meier method). HOXA1 expression on both mRNA
      and protein levels significantly correlated with chemotherapy response. Enforced
      expression of HOXA1 in resistant H69AR cells led to increased chemosensitivity
      through increasing cell apoptosis and cell-cycle arrest. Inhibition of HOXA1
      expression using HOXA1 siRNA in H69 cells resulted in cell resistance to
      therapeutic drugs through reducing drug-induced cell apoptosis accompanied with
      cell cycle arrest. Expression of endogenous miR-100 was significantly elevated in
      resistant H69AR cells and negatively related with HOXA1 expression. The
      expression of HOXA1 in SCLC tissues correlated inversely with the expression
      levels of miR-100. Reporter assays confirmed that miR-100 targeted predicted
      sites in 3'-untranslated region (3'-UTR) of HOXA1 gene. Our data suggested that
      HOXA1-mediated SCLC chemoresistance is under the regulation of miR-100. HOXA1 may
      be a prognostic predictor and potential therapeutic target in human SCLC. 

PMID- 24559686
TI  - A 2 weeks on and 1 week off schedule of sunitinib is associated with decreased
      toxicity in metastatic renal cell carcinoma.
AB  - Treatment of metastatic renal cell carcinoma (mRCC) with sunitinib is often
      associated with toxicity necessitating dose reduction. Maintaining adequate
      dosing and drug levels are essential for optimising clinical efficacy. Standard
      sunitinib schedule is 4 weeks of treatment and 2 weeks of rest (schedule 4/2).
      Empirically, several mRCC patients at The Cleveland Clinic (CCF) have been
      changed from schedule 4/2 to 2 weeks of treatment/1 week off (schedule 2/1) after
      experiencing toxicity, in an attempt to maintain daily dosing. The medical
      records of 30 mRCC patients on sunitinib who were changed from schedule 4/2 to
      schedule 2/1 at CCF were retrospectively reviewed. Toxicity on each schedule was
      recorded during routine clinic visits and graded using Common Toxicity Criteria,
      version 4.0. 97% of patients on schedule 4/2 had grade 3 or 4 toxicity that led
      to changing to schedule 2/1. There were no grade 4 toxicities on schedule 2/1,
      and 27% of patients experienced grade 3 toxicity (p=0.0001). Two of the most
      common toxicities, fatigue and hand-foot syndrome (HFS), were significantly less
      frequent on schedule 2/1 than on schedule 4/2 (p=0.0003; p=0.0004, respectively).
      Median overall treatment duration on schedule 4/2 was 12.6 months (range 1.2
      months-5.1 years) and median overall treatment duration on schedule 2/1 was 11.9
      months (range 0.9+ to 73.3+ months). Treatment with sunitinib on schedule 2/1 is
      associated with significantly decreased toxicity in patients who experience grade
      3 or greater toxicity on schedule 4/2, and can extend treatment duration
      considerably. Prospective clinical trials are required to define the optimal
      sunitinib schedule to balance efficacy and toxicity.

PMID- 24559687
TI  - Novel 1p tumour suppressor Dnmt1-associated protein 1 regulates MYCN/ataxia
      telangiectasia mutated/p53 pathway.
AB  - Neuroblastoma (NB) is a paediatric solid tumour which originates from sympathetic
      nervous tissues. Deletions in chromosome 1p are frequently found in unfavourable
      NBs and are correlated with v-myc avian myelocytomatosis viral oncogene
      neuroblastoma derived homolog (MYCN) amplification; however, it remains to be
      elucidated how the 1p loss contributes to MYCN-related oncogenic processes in NB.
      In this study, we identified the role of Dnmt1-associated protein 1 (DMAP1),
      coded on chromosome 1p34, in the processes. We studied the expression and
      function of DMAP1 in NB and found that low-level expression of DMAP1 related to
      poor prognosis, unfavourable histology and 1p Loss of heterozygosity (LOH) of
      primary NB samples. Intriguingly, DMAP1 induced ataxia telangiectasia mutated
      (ATM) phosphorylation and focus formation in the presence of a DNA damage
      reagent, doxorubicin. By DMAP1 expression in NB and fibroblasts, p53 was
      activated in an ATM-dependent manner and p53-downstream pro-apoptotic Bcl-2
      family molecules were induced at the mRNA level, resulting in p53-induced
      apoptotic death. BAX and p21(Cip1/Waf1) promoter activity dependent on p53 was
      clearly up-regulated by DMAP1. Further, MYCN transduction in MYCN single-copy NB
      cells accelerated doxorubicin (Doxo)-induced apoptotic cell death; MYCN is
      implicated in DMAP1 protein stabilisation and ATM phosphorylation in these
      situations. DMAP1 knockdown attenuated MYCN-dependent ATM phosphorylation and NB
      cell apoptosis. Together, DMAP1 appears to be a new candidate for a 1p tumour
      suppressor and its reduction contributes to NB tumourigenesis via inhibition of
      MYCN-related ATM/p53 pathway activation. 

PMID- 24559688
TI  - Prominent role of cyclic adenosine monophosphate signalling pathway in the
      sensitivity of (WT)BRAF/(WT)NRAS melanoma cells to vemurafenib.
AB  - Vemurafenib improves survival in patients with melanoma bearing the (V600E)BRAF
      mutation, but it did not show any benefit in clinical trials focusing on wild
      type tumours while it may well inhibit (WT)BRAF considering the dosage used and
      the bioavailability of the drug. As tumours may contain a mixture of mutant and
      wild type BRAF cells and this has been also put forward as a resistance
      mechanism, we aimed to evaluate the sensitivity/resistance of six, randomly
      selected, (WT)BRAF/(WT)NRAS lines to vemurafenib and found four sensitive. The
      sensitivity to the drug was accompanied by a potent inhibition of both phospho
      ERK and phospho-AKT, and a significant induction of apoptosis while absent in
      lines with intrinsic or acquired resistance. Phospho-CRAF expression was low in
      all sensitive lines and high in resistant ones, and MEK inhibition can
      effectively potentiate the drug effect. A possible explanation for CRAF
      modulation is cyclic adenosine monophosphate (cAMP), a mediator of melanocortin
      receptor 1 (MC1R) signalling, since it can actually inhibit CRAF. Indeed, we
      measured cAMP and found that all four sensitive lines contained significantly
      higher constitutive cAMP levels than the resistant ones. Consequently,
      vemurafenib and cAMP stimulator combination resulted in a substantial synergistic
      effect in lines with both intrinsic and acquired resistance but only restricted
      to those where cAMP was effectively increased. The use of a cAMP agonist overcame
      such restriction. In conclusion, we report that (WT)BRAF/(WT)NRAS melanoma lines
      with low phospho-CRAF and high cAMP levels may be sensitive to vemurafenib and
      that CRAF inhibition through cAMP stimulation may overcome the resistance to the
      drug. 

PMID- 24559689
TI  - "It is the 'starting over' part that is so hard": Using an online group to
      support hospice bereavement.
AB  - OBJECTIVE: Although hospice agencies are required to provide informal caregivers
      (family or friends of the patient) with formal bereavement support when their
      loved one passes, most bereavement interventions lack standardization and remain
      untested. We employed the Dual Processing Model of Bereavement as a theoretical
      framework for assessing the potential of a secret Facebook group for bereaved
      hospice caregivers. METHOD: A mixed-methods approach was utilized to analyze
      online communication (posts and comments) in the secret Facebook group, and self
      reported outcome measures on depression and anxiety were compared pre- and post
      intervention. RESULTS: Sixteen caregivers participated in the secret Facebook
      group over a period of nine months. The majority of online talk was oriented to
      restoration, revealing abrupt and anticipated triggers that evoked feelings of
      loss. Caregivers also shared loss orientation through storytelling, sharing and
      giving advice, and encouraging others to manage the challenges of coping.
      Caregiver anxiety and depression were lower after the intervention. SIGNIFICANCE
      OF RESULTS: This pilot study provides insight into the use of a secret Facebook
      group to facilitate bereavement support to caregivers. Findings highlight the
      promise of Facebook for hospice bereavement support. Providers and researchers
      are encouraged to explore the positive outcomes associated with bereavement
      support.

PMID- 24559690
TI  - The relation between hepatitis C virus and coronary heart disease.
AB  - It is well known that chronic hepatitis C is associated with insulin resistance
      and metabolic syndrome which are risk factors for atherosclerosis and coronary
      heart disease. As a result, chronic hepatitis C might be thought, through its
      association with metabolic syndrome, to increase the risk of myocardial
      infarction. However, unexpectedly it was found that HCV infection is not
      associated with an increased risk of myocardial infarction. We are providing here
      an hypothesis of the mechanism through which HCV infection does not increase the
      risk for myocardial infarction and also may be protecting against some
      cardiovascular risks that typically develop in many patients with metabolic
      syndrome who do not have chronic hepatitis C. The suggested mechanism includes
      factors that are normal consequences of chronic hepatitis, such as: significant
      decrease in cholesterol and LDL levels; defected blood clotting system; impaired
      myocardial function; decreased venous return and central venous pressure;
      increased nitric oxide and TNF alpha levels; and diminished cardiac beta
      receptors signal transduction. All these factors contribute to a protective
      effect against cardiac ischemia and coronary heart disease. We suggest further
      studies to investigate this hypothesis. 

PMID- 24559691
TI  - Clinical markers of endometriosis: have we been too quick to judge?
AB  - Numerous biochemical differences have been documented in women with endometriosis
      compared to controls; however, identification of a clinically useful marker of
      endometriosis remains elusive. We postulate that the diversity of clinical
      presentations, patient objectives, and complexity of the pathophysiology of
      endometriosis mandates rigorous attention to study design and standardization of
      procedures and questionnaires that has heretofore been overlooked in the pursuit
      of clinical markers of this enigmatic disease. We further propose that it is
      premature to conclude that clinical markers of endometriosis brought forward in
      the literature lack clinical value in the diagnosis of endometriosis. To address
      this hypothesis we reviewed the literature and assessed papers according to a
      modified version of the Quality Assessment of Diagnostic Accuracy Studies
      (QUADAS) criteria from which 55 high quality papers were reviewed. While pelvic
      inflammation and pain is a known significant component of endometriosis, control
      group definitions were widely divergent and included healthy women through to
      women with other inflammatory conditions. Although pain is a common presenting
      complaint in women with endometriosis, it was assessed in only 4 of 55 studies
      (7.3%) whereas infertility was documented in 34/55 studies (61.8%). Disease
      severity was assessed in 44 of 55 studies (80%) whilst the association between
      active vs. inactive disease was attempted in only 2 of the studies reviewed
      (3.6%). We conclude that experimental design criteria are inconsistently applied
      making comparisons across studies difficult. Thus, the clinical utility of
      previously described diagnostic markers of endometriosis remains uncertain. 

PMID- 24559692
TI  - Inter-rectus distance in postpartum women can be reduced by isometric contraction
      of the abdominal muscles: a preliminary case-control study.
AB  - OBJECTIVES: To determine the effect of isometric contraction of the abdominal
      muscles on inter-rectus distance in postpartum women. DESIGN: Preliminary case
      control study. SETTING: Research laboratory. PARTICIPANTS: Ten postpartum women
      {mean age 30 [standard deviation (SD) 4] years; mean weight 58 (SD 7) kg; mean
      height 159 (SD 4) cm} and 10 nulliparous (control) women [mean age 28 (SD 2)
      years; mean weight 56 (SD 6) kg; mean height 160 (SD 6) cm]. INTERVENTIONS:
      Ultrasound images from the anterior abdominal wall were recorded at rest (supine
      position) and during an abdominal isometric contraction, with the subject
      actively performing an abdominal crunch (crook lying position). Two-way analysis
      of variance was used to compare the inter-rectus distance between groups
      (postpartum vs control) and between levels of abdominal muscle activation (rest
      vs isometric contraction). MAIN OUTCOME MEASURES: Inter-rectus distance 2cm above
      the level of the umbilicus. RESULTS: The inter-rectus distance was significantly
      greater in the postpartum group compared with the control group [14.7 (SD 3.1) mm
      vs 9.6 (SD 2.8) mm; mean difference 5.1mm; 95% confidence interval (CI) 3.4 to
      6.8]. The inter-rectus distance was significantly lower during isometric
      contraction compared with rest [10.7 (SD 3.1) mm vs 13.4 (SD 3.1) mm; mean
      difference 2.8mm; 95% CI 1.2 to 4.5]. No interaction was found between group and
      muscle contraction. CONCLUSIONS: The inter-rectus distance was significantly
      higher in postpartum women compared with controls, and significantly lower during
      isometric contraction of the abdominal muscles (abdominal crunch) compared with
      rest.

PMID- 24559693
TI  - Large scale synthesis of Janus nanotubes and derivative nanosheets by selective
      etching.
AB  - One-dimensional Janus nanotubes have been successfully synthesized in large
      quantity by selective etching of the interior Al2O3 from hydrophobically modified
      halloysite nanotube with the exterior surface preserved. By simply tuning the
      etching time, the colloid shape evolves from nanotubes to partially collapsed
      nanotubes and porous nanorods. The microstructure and chemical composition of the
      etched hydrophobically modified halloysite are characterized by transmission
      electron microscopy (TEM), scanning electron microscopy (SEM), X-ray diffraction
      (XRD), FT-IR spectrophotometer and nitrogen adsorption-desorption. The results
      indicate the interior Al2O3 can be controlled etched. Labeling experiments
      demonstrate the hydrophilic nanoparticles are predominantly located onto the
      coarse region of the etched nanotubes. Selective etching of hydrophobically
      modified halloysite creates Janus nanotubes with a hydrophobic exterior surface
      and a hydrophilic interior surface. An enhanced capacity for emulsification of
      the Janus nanotubes toward immiscible mixture is shown. Furthermore, by a
      favorable growth of other functional materials, composition of the Janus
      nanotubes can be further extended, enabling different applications from magnetic
      separation to water purification, drug immobilization and controlled release.
      After crushing the Janus nanotubes, derivative nanosheets are derived. The method
      can be scaled up and economical compared with other method, which is the key to
      further exploit practical application. 

PMID- 24559694
TI  - Electrochemical modelling of QD-phospholipid interactions.
AB  - HYPOTHESIS: The aggregation of quantum dots (QDs) and capping of individual QDs
      affects their activity towards biomembrane models. EXPERIMENTS: Electrochemical
      methods using a phospholipid layer on mercury (Hg) membrane model have been used
      to determine the phospholipid monolayer activity of thioglycollic acid (TGA)
      coated quantum dots (QDs) as an indicator of biomembrane activity. The particles
      were characterised for size and charge. FINDINGS: The activity of the QDs towards
      dioleoyl phosphatidylcholine (DOPC) monolayers is pH dependent, and is most
      active at pH 8.2 within the pH range 8.2-6.5 examined in this work. This pH
      dependent activity is the result of increased particle aggregation coupled to
      decreasing surface charge emanating from the TGA carboxylic groups employed to
      stabilize the QD dispersion in aqueous media. Capping the QDs with CdS/ZnS lowers
      the particles' activity to phospholipid monolayers.

PMID- 24559695
TI  - Preparation and characterization of PdO nanoparticles on trivalent metal (B, Al
      and Ga) substituted MCM-41: excellent catalytic activity in supercritical carbon
      dioxide.
AB  - Palladium oxide (PdO) nanoparticles supported on B, Al and Ga modified mesoporous
      MCM-41with different Si/M ratios (where, M=B, Al or Ga) varied from 100 to 5 was
      synthesized in one-pot. Developed materials were characterized by several
      techniques such as XRD, TEM, UV-Vis, XPS and TG-DTA. A highly ordered structure
      was revealed by XRD for all the support materials depending on Si/M ratio. TEM
      analysis evidenced the presence of spherical PdO particles. Interestingly, the
      particle sizes correlated well with Si/M ratio as well as the nature of M.
      Spectroscopic characterization of calcined materials suggested the presence of
      Pd(2+), whereas XPS confirmed the existence of Pd(2+) in PdO form. The catalytic
      activity of resultant materials was investigated by the chemoselective
      hydrogenation of chloronitrobenzene in supercritical carbon dioxide. All the
      materials exhibit excellent conversion of chloronitrobenzene and selectivity to
      chloroaniline within the reaction time of 50 min. at 35  degrees C. Substitution
      of Si by trivalent metal cation improved the catalytic performance of B and Ga
      containing catalysts. Among the three catalysts, superior catalytic activity was
      observed for Pd/B-MCM-41 with highest conversion (100%) and selectivity to
      chloroaniline (100%) and thus, followed the reactivity order of
      PdO/B>PdO/Ga>PdO/Al. Considering o-, m- and p-chloronitrobenzene, for all the
      materials conversion followed the order of p->m->o-, whereas selectivity to
      chloroaniline for all three isomers were strongly influenced by the trivalent
      metal ion in the support material.

PMID- 24559696
TI  - Microwave-assisted hydrothermal synthesis and temperature sensing application of
      Er3+/Yb3+ doped NaY(WO4)2 microstructures.
AB  - Laurustinus shaped NaY(WO4)2 micro-particles assembled by nanosheets were
      synthesized via a microwave-assisted hydrothermal (MH) route. The growing
      mechanisms for the obtained resultants with various morphologies were proposed
      based on the observation of scanning electron microscopic (SEM) images. It was
      found that Na3Cit added into the reaction solution greatly influenced the
      formation and size dimension of the nano-sheets, furthermore determined
      assembling of the laurustinus shaped micro-particles. The temperature sensing
      performance of NaY(WO4)2:Er(3+)/Yb(3+) was evaluated. Thermal effect induced by
      the 980nm laser irradiation in laurustinus-shaped NaY(WO4)2:Er(3+)/Yb(3+)
      phosphor was studied. It was found that the green upconversion luminescence
      intensity increased in the first stage of laser irradiation, and then decreased
      after reaching a maximum. Based on the thermal sensing technology the laurustinus
      NaY(WO4)2:Er(3+)/Yb(3+) microparticles were used as thermal probe to discover
      thermal effect of upconversion luminescence in laurustinus
      NaY(WO4)2:Tm(3+)/Yb(3+) micro-particles. 

PMID- 24559697
TI  - Surface force measurements at kaolinite edge surfaces using atomic force
      microscopy.
AB  - Fundamental results obtained from research on the properties of the edge surfaces
      of kaolinite particles (~500 nm) are reported. Of particular significance was the
      development of the experimental protocol. Well-ordered kaolinite edge surfaces
      were prepared as an epoxy resin sandwich structure having layered kaolinite
      particles in the center of the epoxy resin sandwich. Images of the sectioned
      kaolinite edge surfaces were examined by atomic force microscopy (AFM), and the
      average thickness of kaolinite particles in this study was determined to be 38.3
      nm+/-11.7 nm. Furthermore, the surface charge of the kaolinite edge surfaces was
      evaluated with a super sharp Si tip. The point of zero charge (PZC) of the
      kaolinite edge surface was determined to be below pH 4, in contrast to the
      traditional view that the edge surfaces of kaolinite particles may carry a
      positive charge at pH 4. This lower PZC of the kaolinite edge surface was
      attributed to the lack of isomorphous substitution in the silica tetrahedral
      layer when compared to the PZC for the muscovite edge surface. Our results are
      consistent with the particle aggregation and flotation behavior of kaolinite, and
      should provide the basis for improved flotation strategies leading to the
      efficient recovery and utilization of mineral and energy resources.

PMID- 24559698
TI  - Synthesis and in situ observation of 3D superlattices of gold nanoparticles using
      oil-in-water emulsion.
AB  - In this work oil-in-water emulsion has been successfully used as a confined
      environment to grow 3D superlattices of gold nanoparticles. The superlattices
      were grown from 5 nm uniform gold nanoparticles using slow destabilization
      method. The confined environment was created by forming a stable emulsion where
      the gold colloid suspended in toluene was used as oil phase. Superlattices were
      also formed in bulk solution using the same slow destabilization method. A
      comparative study reveals that compact superlattices form more readily inside the
      emulsion drops as compared to bulk precipitation. The unstable colloid (in bulk
      or as emulsion) was aged for various periods at 5  degrees C to form more compact
      superlattices. The best superlattices with sharp corners are observed when the
      superlattices are formed inside the emulsion and aged for a month. Two key
      parameters, the incubation temperature and anti-solvent concentration, are
      optimized to obtain larger superlattices with sharp features. A new method is
      also demonstrated for in situ observation of superlattice formation using an
      optical microscope.

PMID- 24559699
TI  - Experimental studies on irreversibility of electrostatic adsorption of silica
      nanoparticles at solid-liquid interface.
AB  - Adsorption of colloidal nanoparticles (NPs) at solid-liquid interface is a
      scientifically interesting and technologically important phenomenon due to its
      fundamental importance in many industrial, environmental, and biological
      processes, such as wastewater treatment, printing, coating of surfaces,
      chromatography, papermaking, or biocompatibility. The process is well understood
      theoretically by the random sequential adsorption (RSA) model, based on the
      assumption of irreversible adsorption. Irreversible adsorption is defined as a
      process in which, once adsorbed, a particle can neither desorb, nor to move
      laterally on the surface. However, published experimental data that verifies the
      irreversibility of particle adsorption are very limited. In this study, we
      demonstrate the irreversibility of electrostatically driven nanoparticle
      adsorption utilizing a carefully selected set of experiments. A simple method was
      employed by uniquely introducing Ag@SiO2 core/shell NPs to perform exchange
      adsorptions experiments. Stober SiO2 NPs with a diameter of 50-80 nm were
      initially electrostatically adsorbed onto amino-functionalized silicon wafer
      substrates followed by the subsequent adsorption of Ag@SiO2 NPs. The Ag@SiO2 NPs
      have the same surface chemistry as the neat SiO2 NPs. For the second step the
      adsorption time was varied from 1 min to 1 week so as to get a thorough
      understanding of the process irreversibility. Surface coverage quantification has
      shown that the surface coverage of the initially adsorbed SiO2 NPs stays the same
      independent of the duration of the second step adsorption using the Ag@SiO2
      core/shell NPs. This observation directly confirms the irreversibility of
      electrostatic adsorption of NPs.

PMID- 24559700
TI  - New methodology based on static light scattering measurements for evaluation of
      inhibitors for in bulk CaCO3 crystallization.
AB  - In the present work a new procedure for evaluation of scale inhibitor for calcium
      carbonate is proposed based on continuous measurement of particle size
      distribution by laser diffraction technique and simultaneous pH recording. From
      data obtained during real-time monitoring of the homogeneous nucleation and
      growth of CaCO3 particles formed in the bulk phase after the addition of
      carbonate ions to synthetic formation water (AF-W2), it was possible to evaluate
      the performance of four inhibitors classified in two groups: phosphonates
      (ethylenediamine tetramethylene phosphonic acid, EDTMP; diethylenetriamine
      pentamethylene phosphonic acid, DETPMP) and polymeric inhibitors (phosphino poly
      carboxylic acid, PPCA; polyvinyl sulfonate, PVS). The comparative bulk
      crystallization inhibition efficiency for the evaluated inhibitors, under the
      experimental conditions used in this work, increases in the following order:
      EDTMP<DETPMP<PVS?PPCA. Moreover, this methodology allowed the deduction of the
      main mechanism of their inhibiting action: nucleation inhibition or crystal
      growth retardation. 

PMID- 24559701
TI  - Well-defined plate and hollow disk shaped particles of silica
      dialkyldimethylammonium hybrids.
AB  - Well-defined plate and hollow disk of silica-dioctadecyldimethylammonium hybrid
      particles were obtained by the sol-gel reaction of tetraethoxysilane in the
      presence of dioctadecyldimethylammonium chloride, where synthetic condition was
      determined based on the Stober synthesis for micron size silica sphere. The
      particle size was several hundreds of nm in the radius and several tens of nm in
      the thickness. X-ray powder diffraction patterns indicated that the products
      possess layered mesostructures, which were thought to be directed by the lamellar
      aggregates of dioctadecyldimethylammonium. 

PMID- 24559702
TI  - The electrophoretic mobility of an uncharged particle.
AB  - HYPOTHESIS: It has been claimed that uncharged particles can have negative
      electrophoretic mobilities, and so a negative mobility need not imply a negative
      particle charge. We show that although a steady electrophoresis may be possible
      for the uncharged infinite slabs studied in Molecular Dynamics simulations, it is
      not possible for a finite particle. EXPERIMENTS AND THEORY: An uncharged particle
      may initially move when the field is turned on, but our analysis shows that this
      motion ceases as charges of opposite sign build up on the front and back of the
      particle. Uncharged particles may move in alternating electric fields, but their
      mobility is predicted to increase with electrolyte conductivity. Experimentally,
      however, the mobility of hexadecane oil drops in water at pH 9 decreases with
      increasing NaCl concentrations. FINDINGS: Our results are consistent with the
      usual compression of the double layer with added salt, and with the traditional
      interpretation, that hydrophobic particles have negative mobilities because they
      are negatively charged. Uncharged particles may have a transient mobility but it
      is quickly quenched by polarisation of the double layer.

PMID- 24559703
TI  - Magnetic mesoporous Fe/carbon aerogel structures with enhanced arsenic removal
      efficiency.
AB  - Wastewater treatment has drawn significant research attention due to its
      associated environmental issues. Adsorption is a promising method for treating
      wastewater. The development of an adsorbent with a high surface area is
      important. Therefore, we successfully developed mesoporous Fe/carbon aerogel (CA)
      structures with high specific surface areas of 48 7m(2)/g via the carbonization
      of composite Fe3O4/phenol-formaldehyde resin structures, which were prepared
      using a hydrothermal process with the addition of phenol. The mesoporous Fe/CA
      structures were further used for the adsorption of arsenic ions with a maximum
      arsenic-ion uptake of calculated 216.9 mg/g, which is higher than that observed
      for other arsenic adsorbents. Ferromagnetic behavior was observed for the as
      prepared mesoporous Fe/CA structures with an excellent response to applied
      external magnetic fields. As a result, the adsorbent Fe/CA structures can be
      easily separated from the solution using an external magnetic field. This study
      develops the mesoporous Fe/CA structures with high specific surface areas and an
      excellent response to an applied external magnetic field to provide a feasible
      approach for wastewater treatment including the removal of arsenic ions.

PMID- 24559704
TI  - Influence of electrostatic particle interactions on the properties of particulate
      coatings of titanium dioxide.
AB  - HYPOTHESIS: Particulate coatings are used in a wide range of technical
      applications. The application affecting properties of these coatings depend
      strongly on the structure formation along the production process. Thus, primary
      and secondary particle size, size distribution, particle morphology as well as
      the particle-particle and particle-fluid interactions of the used formulation
      affect the resulting coating properties. EXPERIMENTS: In this investigation
      titanium dioxide particles were dispersed in ethanol with a stirred media mill
      and stabilised electrostatically. Subsequently, the suspension was destabilised
      to reach specific pH* values and processed into coatings by dip coating. The
      influence of the pH* value of the suspension on the suspension's properties such
      as viscosity, agglomerate size and zeta potential and on its application
      properties such as coating thickness, micro-mechanical properties, abrasion
      resistance, gloss, roughness and adhesion was examined. FINDINGS: The
      electrostatic particle interactions show a significant influence on the structure
      formation as well as on the properties of nanoparticulate coatings. The coating
      properties are affected by the coating structures on micro-, meso- or macroscopic
      scale. Selective coating properties were related to the coating structure using
      the theoretical model of Rumpf. Besides other important process and formulation
      parameters, for the production of homogeneous, functional coatings with the
      desired properties a precise adjustment of the particle interactions is
      necessary.

PMID- 24559705
TI  - Zwitterionic hyperbranched polyester functionalized cardiovascular stent and its
      biocompatibility.
AB  - Zwitterionic hyperbranched polyester (HBPE) synthesized on bare metal stents
      (BMS) surface by surface-initiated atom transfer radical polymerization (SI-ATRP)
      method. The modified BMS obtained was tested for its blood compatibility. The
      blood compatibility studies were including, platelet adhesion tests, hemolysis
      assay, morphological changes in RBCs, coagulation tests, PRT assay, complement
      activation, platelet activation, and the cytotoxicity was also investigated. The
      modified BMS surface does not cause platelets adherent, red blood cell
      disruption, hemolysis and does not induce complement and platelets activation.
      All results indicated that the modified BMS was blood compatible and no
      cytotoxicity. It has the potential use for biomedical applications. 

PMID- 24559706
TI  - Superhydrophobic surface of TiO2 hierarchical nanostructures fabricated by Ti
      anodization.
AB  - A hierarchical structure of TiO2 with disordered nanowires on top of regular
      nanotubes was fabricated. With organic monolayers, it showed stronger
      superhydrophobic properties than regular nanotubes. The surface roughness was
      further enhanced by removing the dense nanowires layer, resulting in 172 degrees 
      water contact angle. The potential application for aquatic devices was explored
      by the treated Ti mesh which showed striking floating stability. 

PMID- 24559707
TI  - Infrared, Raman and NMR investigations of risedronate adsorption on
      nanocrystalline apatites.
AB  - The aim of the current work was to study the physico-chemical interactions of a
      bisphosphonate molecule, risedronate, with a well-characterised synthetic
      nanocrystalline apatite (NCA) as a model bone mineral. We adopted a global
      approach, using complementary physico-chemical techniques such as FTIR, RAMAN and
      NMR spectroscopies in order to learn more about the interaction process of
      risedronate with the apatitic surface. The results obtained suggest that
      risedronate adsorption corresponds to an ion substitution reaction with phosphate
      ions occurring at the crystal surface. This mechanism explains the greater amount
      adsorbed (N) for NCA, compared to well crystallised stoichiometric
      hydroxyapatite, attributable to the well-developed hydrated layer at the surface
      of the nanocrystals. However, most calcium ions remain attached to the solid
      phase and the formation of insoluble risedronate calcium salts must also be
      considered as a competitive reaction to the adsorption. Thus a calcium
      risedronate salt was synthesised and fully characterised for comparison to the
      solids after adsorption. Following spectroscopic results, it can be concluded
      that a strong interaction was established between risedronate ions and calcium
      ions at the apatitic surface. However, under these experimental conditions there
      is no nucleation of a distinct calcium risedronate salt and the apatite crystals
      retain their integrity. 

PMID- 24559708
TI  - Fabrication of honeycomb-patterned porous films from PS-b-PNIPAM amphiphilic
      diblock copolymers synthesized via RITP.
AB  - Poly(styrene)-b-poly(N-isopropylacrylamide) (PS-b-PNIPAM) amphiphilic diblock
      copolymers were synthesized via reverse iodine transfer polymerization (RITP)
      firstly. And then the honeycomb structured porous films were fabricated by drop
      the amphiphilic diblock copolymer solutions on glass substrates. The porous films
      were characterized using field emission scanning electron microscopy (FESEM) and
      atomic force microscopy (AFM), respectively. The results showed that the regular
      honeycomb patterned porous film was achieved successfully by employing the block
      copolymer with a significantly larger polystyrene block proportion into the
      solution and the pore diameter of the film decreases obviously with the polymer
      concentration increased. The effects of airflow speed and Ag particles on porous
      films are also discussed in this study. 

PMID- 24559709
TI  - Facile fabrication of transparent, broadband photoresponse, self-cleaning
      multifunctional graphene-TiO2 hybrid films.
AB  - We reported a novel approach to fabricate graphene-TiO2 hybrid films by
      combination of the layer-by-layer (LbL) assembly and the surface sol-gel (SSG)
      process. The reduced graphene oxide (RGO) nanosheets and films were characterized
      by means of transmission electron microscopy, Raman spectroscopy, UV-visible
      absorbance spectroscopy, contact angle/interface system, and four-point probe. It
      was found that the graphene-TiO2 hybrid film showed enhanced photoresponse
      performance compared with RGO thin film and TiO2 thin film. The photoresponse
      properties of hybrid films could be manipulated by variation of the cycle numbers
      of RGO LbL assembly and titanium precursor SSG process. Photoinduced
      superhydrophility of the hybrid film was shown under broadband light
      illumination. The obtained transparent, superhydrophilic and conductive graphene
      TiO2 hybrid film showed excellent photoresponse, antifogging, and antistatic
      behaviors. 

PMID- 24559710
TI  - Europium phosphomolybdate and osmium metallopolymer multi-functional LbL films:
      redox and electrocatalytic properties.
AB  - Hybrid multilayer films composed by osmium metallopolymer [Os(bpy)2(PVP)10Cl]Cl
      (Os-poly) and europium phosphomolybdate, K11[Eu(III)(PMo11O39)2] (Eu(PMo11)2),
      were prepared using the electrostatic layer-by-layer (LbL) self-assembly method.
      The film build-up, monitored by electronic spectroscopy, showed a regular
      stepwise growth indicating a strong interaction between layers. The XPS
      measurements corroborated the successful fabrication of the hybrid films with the
      Os-poly/Eu(PMo11)2 composition. SEM images revealed a completely covered surface
      with a highly roughened texture. Electrochemical characterisation of films by
      cyclic voltammetry revealed three Mo-based reduction processes (Mo(VI)->Mo(V)) in
      the potential range between -0.4 and 0.1 V and one Os reduction process (Os(III)
      >Os(II)) at ~0.270 V. The cyclic voltammograms of two electroactive probes,
      [Fe(CN)6](3-/4-) and [Ru(NH3)6](3+/2+) on {Os-poly/Eu(PMo11)2}n modified
      electrodes revealed redox mediation between film and the probes. Furthermore, the
      {Os-poly/Eu(PMo11)2}n multilayer films also showed excellent Mo-based
      electrocatalytic activity towards reduction of nitrite and iodate, confirming the
      multi-functional properties of the hybrid europium phosphomolybdate - osmium
      metallopolymer LbL films.

PMID- 24559711
TI  - Adsorption study of an organo-arsenical with chitosan-based sorbents.
AB  - In this study, chitosan-based copolymers were prepared at various weight ratios
      of chitosan (C) to glutaraldehyde (G): 1:1 (CG11), 2:1 (CG21), and 3:1 (CG31).
      The sorption properties of these copolymers were investigated with roxarsone in
      simulated aquatic conditions at pH 7 in phosphate buffer, similar to that found
      in poultry litter leachate. The relative sorption capacity (Q(m); mmol/g) of the
      sorbents are listed in parentheses in descending order: CG11 (1.80)>CG31
      (0.945)>CG21 (0.802)>chitosan (0.416). The sorptive properties of the copolymers
      are comparable to granular activated carbon (GAC), a standard carbonaceous
      sorbent material, where Q(m)=2.36 mmol/g. The adsorption properties of phenolic
      adsorbates such as o-nitrophenol, p-nitrophenol, and roxarsone with the CG
      copolymers and GAC were investigated at various pH and compared with phosphate
      and carbonate buffer systems.

PMID- 24559712
TI  - Adsorption of silver ions on polypyrrole embedded electrospun nanofibrous
      polyethersulfone membranes.
AB  - In this study we developed polypyrrole embedded electrospun nanofibrous
      polyethersulfone nanofibrous membranes for the removal of silver ions.
      Polypyrrole and polyethersulfone dissolved in N-methyl-2-pyrrolidone (NMP) were
      electrospun into nanofibrous membranes via an electrospinning process. The
      morphology of as-spun polypyrrole/polyethersulfone nanofibers was examined by
      scanning electron microscopy. The average diameter of electrospun nanofibers
      ranged from 410 nm to 540 nm. The adsorption capability of nanofibrous
      polypyrrole/polyethersulfone membranes was measured and compared with that of
      bulk polypyrrole. The influence of various process conditions on adsorption
      efficiency was also examined. The experimental results suggested that the
      electrospun nanofibrous membranes exhibited good silver ion uptake capabilities.
      The metal uptake of nanofibrous membranes increased with the initial metal ion
      concentrations and the pH value, while decreased with the temperature and the
      filtering rate of the solutions. Furthermore, the electrospun membrane could be
      reused after the recovery process.

PMID- 24559713
TI  - Analytical and numerical study of the electro-osmotic annular flow of
      viscoelastic fluids.
AB  - In this work we present semi-analytical solutions for the electro-osmotic annular
      flow of viscoelastic fluids modeled by the Linear and Exponential PTT models. The
      viscoelastic fluid flows in the axial direction between two concentric cylinders
      under the combined influences of electrokinetic and pressure forcings. The
      analysis invokes the Debye-Huckel approximation and includes the limit case of
      pure electro-osmotic flow. The solution is valid for both no slip and slip
      velocity at the walls and the chosen slip boundary condition is the linear Navier
      slip velocity model. The combined effects of fluid rheology, electro-osmotic and
      pressure gradient forcings on the fluid velocity distribution are also discussed.

PMID- 24559714
TI  - Cation exchange resin immobilized bimetallic nickel-iron nanoparticles to
      facilitate their application in pollutants degradation.
AB  - Nanoscale zerovalent iron (nZVI) usually suffers from reduction of reactivity by
      aggregation, difficulty of assembling, environmental release and health concerns.
      Furthermore, data are lacking on the effect of cheap nickel on debromination of
      decabromodiphenyl ether (DBDE) by immobilized nZVI in aqueous system. In this
      study, strong acid polystyrene cation-exchange resins with particle diameter from
      0.4 to 0.6 mm were utilized as matrices to immobilize bimetallic nickel-iron
      nanoparticles in order to minimize aggregation and environmental leakage risks of
      nZVI and to enhance their reactivity. Elemental distribution mapping showed that
      iron particles distributed uniformly on the surface of the resin and nickel
      particles were dispersed homogeneously into Fe phase. The reaction rate of resin
      bound nZVI is about 55% higher than that of dispersed nZVI. The immobilized
      bimetallic nanoparticles with 9.69% Ni had the highest debromination percent
      (96%) and reaction rate (0.493 1/h). The existence of Ni significantly improved
      the debromination rate, due to the surface coverage of catalytic metal on the
      reductive metal and the formation of a galvanic cell. The environmental dominant
      congeners, such as BDE 154, 153, 100, 99 and 47, were produced during the
      process. Outstanding reactive performance, along with magnetic separation assured
      that resin-bound bimetallic nickel-iron nanoparticles are promising material that
      can be utilized to remediate a wide variety of pollutants contaminated sites
      including polybrominated diphenyl ethers.

PMID- 24559715
TI  - Influence of ionic liquids on the critical micellization temperature of a tri
      block co-polymer in aqueous media.
AB  - To explore the role of additives in controlling the critical micellization
      temperature (CMT) of a block copolymer in aqueous solution, in the present work,
      a series of ionic liquids (ILs) containing the same cation, 1-butyl-3
      methylimidazolium, bmim(+) and commonly used anions such as SCN(-), BF4(-), I(-),
      Cl(-), CH3COO(-) and HSO4(-) were chosen for study with a triblock copolymer,
      poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol),
      (PEG-PPG-PEG) in aqueous solution. The present results suggest that the ability
      of ILs for decreasing the polymer CMT is mainly a result of not only from charge
      and size of anions of the ILs, but also due to the weak ion-ion pair interactions
      within IL. The present study provides important information that can be helpful
      to tune the IL- or temperature-sensitive copolymer CMT and micelle shapes which
      are crucial for understanding the drug delivery mechanisms. 

PMID- 24559716
TI  - Adsorption of polyalkyl glycol ethers and triblock nonionic polymers on PET.
AB  - Surface modification enables fiber lubrication and processing but little is known
      about the extent and dynamics of adsorption of typical adsorbates applied for
      such purposes, which often includes water-soluble block nonionic amphiphilic
      polymers. In this work we used quartz crystal microgravimetry (QCM) to
      investigate the adsorption on poly(ethylene terephthalate) (PET) of polyalkyl
      glycol ethers and triblock molecules of ethylene oxide and propylene oxide. The
      adsorption from aqueous solution of the block nonionic amphiphilic polymers
      strongly correlated with the self-association driven by the chain length of the
      respective hydrophobic blocks. This was demonstrated for the different adsorbing
      polymers using hydrophobic numbers calculated from simple group contribution
      methods. Hydrophobic and van der Waals interactions explain the affinity of the
      nonionic polymers with PET, which lead to adsorption isotherms that follow
      Langmuir-based and one-step empirical adsorption models. 

PMID- 24559717
TI  - Nanoscale surface characterization of biphasic calcium phosphate, with
      comparisons to calcium hydroxyapatite and beta-tricalcium phosphate bioceramics.
AB  - OBJECTIVES: It is our aim to understand the mechanisms that make calcium
      phosphates, such as bioactive calcium hydroxyapatite (HA), and biphasic calcium
      (BCP) and beta-tricalcium (beta-TCP) phosphates, desirable for a variety of
      biological applications, such as the filling of bone defects. METHODS: Here, we
      have characterized these materials by X-ray photoelectron spectroscopy (XPS), X
      ray diffraction (XRD), scanning electron microscopy (SEM), Fourier-transform
      infrared (FTIR), time-of-flight secondary ion mass spectroscopy (TOF-SIMS) and
      laser granulometry. RESULTS: SEM shows clearly that BCP is a matrix made of macro
      organized microstructure, giving insight to the specially chosen composition of
      the BCP that offers both an adequate scaffold and good porosity for further bone
      growth. As revealed by laser granulometry, the particles exhibit a homogeneous
      size distribution, centered at a value somewhat larger than the expected 500 MUm.
      XPS has revealed the presence of adventitious carbon at all sample surfaces, and
      has shown that Ca/P and O/Ca ratios in the outer layers of all the samples differ
      significantly from those expected. A peak-by-peak XPS comparison for all samples
      has revealed that TCP and BCP are distinct from one another in the relative
      intensities of their oxygen peaks. The PO3(-)/PO2(-) and CaOH+/Ca+ TOF-SIMS
      intensity ratios were used to distinguish among the samples, and to demonstrate
      that the OH- fragment, present in all the samples, is not formed during
      fragmentation but exists at the sample surface, probably as a contaminant.
      CONCLUSIONS: This study provides substantial insight into the nanoscale surface
      properties of BCP, HA and beta-TCP. Further research is required to help identify
      the effect of surfaces of these bioceramics with proteins and several biological
      fluids. CLINICAL RELEVANCE: The biological performance of implanted synthetic
      graft bone biomaterials is strongly influenced by their nanosurface
      characteristics, the structures and properties of the outer layer of the
      biomaterial.

PMID- 24559718
TI  - Intermittent urethral catheterization-descriptive study at a Brazilian service.
AB  - AIMS AND BACKGROUND: The rehabilitation process of patients with neurogenic
      bladder involves psychosocial, cultural, political and economic human factors,
      representing a challenge for patients/caregivers as well as health professionals.
      This study was aimed at characterizing patients with neurogenic bladder who use
      intermittent urethral catheterization and were going through rehabilitation at a
      teaching hospital. METHOD: This descriptive study was undertaken in the interior
      of Sao Paulo State-Brazil. All ethical guidelines were complied with. To collect
      the data, interviews were held during nursing consultations with patients more
      than 18years of age suffering from neurogenic bladder who used intermittent
      urethral catheterization. RESULTS: Most patients had spinal cord trauma, are
      single, male and gain a low income. They have been using catheterization for
      several years, at irregular frequencies, using polyethylene catheters.
      CONCLUSIONS: No standardization exists in the accomplishment of the practices
      used and strategies are needed to remodel the service.

PMID- 24559719
TI  - Evaluation of recovery in lip closing pressure and occlusal force and contact
      area after orthognathic surgery.
AB  - PURPOSE: The purpose of this study was to evaluate the relationship between lip
      closing force, occlusal contact area and occlusal force after orthognathic
      surgery in skeletal Class III patients. SUBJECTS AND METHODS: The subjects
      consisted of 54 patients (28 female and 26 male) diagnosed with mandibular
      prognathism who underwent sagittal split ramus osteotomy with and without Le Fort
      I osteotomy. Maximum and minimum lip closing forces, occlusal contact area and
      occlusal force were measured pre-operatively, 6 months and 1 year post-operative.
      RESULTS: Maximum and minimum lip closing forces, occlusal contact area and
      occlusal force increased with time after surgery, however a significant increase
      was not found in the occlusal contact area in women. In increased ratio (6
      months/pre-operative and 1 year/pre-operative), the maximum lip closing force was
      significantly correlated with the occlusal contact area (P < 0.0001).
      CONCLUSIONS: This study suggested that orthognathic surgery could improve the
      occlusal force, contact area and lip closing force, and an increase ratio in
      maximum lip closing force was associated with an increased ratio in occlusal
      contact area.

PMID- 24559720
TI  - Family-based analysis of adiponectin gene polymorphisms in Chinese Han polycystic
      ovary syndrome.
AB  - OBJECTIVE: To study the association between two single-nucleotide polymorphisms
      (SNPs) variants (rs2241766 and rs1501299) of the adiponectin gene (ADIPOQ) and
      polycystic ovary syndrome (PCOS) in PCOS family trios. DESIGN: Family-based
      study. SETTING: University hospital. PATIENT(S): A total of 224 unrelated PCOS
      probands, their biologic parents, and 204 control subjects. INTERVENTION(S):
      Anthropometric, hormonal, and metabolic assessment; genotype detection. MAIN
      OUTCOME MEASURE(S): Basic endocrine, serum fasting glucose (FG), fasting insulin
      (FINS), total cholesterol (TC), triglycerides (TG), and low-density lipoprotein
      (LDL) and high-density lipoprotein (HDL) cholesterol levels were measured. The
      transmission disequilibrium test (TDT) was used to analyze the association
      between two SNPs of ADIPOQ and PCOS. RESULT(S): A significant positive
      association was detected between SNP rs1501299 and PCOS. Compared with AA
      genotype, AC and CC genotypes had increased risk for PCOS, and the difference
      remained significant after adjustment for age, body mass index, and testosterone
      (T). The levels of T, TG, HDL cholesterol, and FINS were significantly higher in
      obese PCOS patients. However, we failed to find significant overtransmission of
      the other SNP, rs2241766, from parents to PCOS offspring. The genotype
      frequencies of rs2241766 and rs1501299 were not different in obese and lean PCOS
      patients and their parents. CONCLUSION(S): TDT confirms that SNP rs1501299 in the
      ADIPOQ is significantly associated with the risk of PCOS in the Chinese Han
      population. The present data may provide a basis for further studies of the role
      of the ADIPOQ in the etiology of PCOS.

PMID- 24559721
TI  - Stimulation of mitochondrial embryo metabolism by dichloroacetic acid in an aged
      mouse model improves embryo development and viability.
AB  - OBJECTIVE: To determine whether supplementation of embryo culture media with a
      substrate to stimulate mitochondrial activity improves embryo viability and
      pregnancy establishment in aged mice. DESIGN: Female mice were superovulated and
      mated. Zygotes were collected and cultured in either G1/G2 or G1/G2 with 1.0 mM
      dichloroacetic acid (DCA), a stimulator of pyruvate dehydrogenase complex.
      Embryos were cultured to the blastocyst stage and transferred into pseudopregnant
      female mice. SETTING: University research facility. ANIMAL(S): Swiss female mice
      26- to 28-week-old. INTERVENTION(S): The addition of DCA to the embryo culture
      media. MAIN OUTCOME MEASURE(S): Embryo development, total, trophectoderm, inner
      cell mass (ICM) and epiblast cell number, mitochondrial membrane potential,
      reactive oxygen species, pyruvate oxidation, adenosine triphosphate (ATP) output,
      implantation rates, and fetal and placental size and weights. RESULT(S):
      Supplementation of the embryo culture medium with DCA significantly increased
      blastocyst development rates in vitro, significantly improved total,
      trophectoderm, and ICM cell numbers and pluripotency of the ICM, significantly
      increased pyruvate oxidation and ATP output, and significantly increased fetal
      weights and size comparable to in vivo conditions. CONCLUSION(S): This study
      demonstrates that the addition of DCA to embryo culture media improves
      mitochondrial output in embryos produced from aged mice. Although DCA itself may
      be of limited therapeutic value in a clinical setting due to its low threshold of
      dosage and high toxicity, this proof of concept study does suggest that the
      addition of a physiological-based mitochondrial stimulator to embryo culture
      media for aged women may potentially improve IVF outcomes.

PMID- 24559722
TI  - Characterization of a mechanism to inhibit ovarian follicle activation.
AB  - OBJECTIVE: To demonstrate that a small molecule can induce the transcription
      factor Foxo3 in the ovary and lead to inhibition of follicle activation. DESIGN:
      Cell culture, organ culture, and animal studies. SETTING: University-based
      laboratory. ANIMAL(S): 23 female C57BL/6 mice. INTERVENTION(S): Human ovary cells
      and mouse ovaries in culture treated with 2-deoxyglucose (2-DG) to mimic glucose
      deprivation, and mice intraperitoneally injected with 100 mg/kg, 300 mg/kg, or
      600 mg/kg 2-DG daily for 2 weeks. MAIN OUTCOME MEASURE(S): In cell and organ
      culture, Foxo3 expression analyzed by quantitative reverse-transcriptase
      polymerase chain reaction (qRT-PCR); in treated animals, expression of genes
      regulated by nutrient deprivation (Foxo3, ATF4, GRP78, CHOP, ASNS, c-Myc)
      measured in brain, kidney, and ovary by qRT-PCR; and ovarian follicles
      histologically classified and counted. RESULT(S): Foxo3 expression is induced by
      2-DG at both the mRNA and protein level in human ovarian cell culture, possibly
      through ATF4-dependent gene regulation. Foxo3 expression is also induced by 2-DG
      in ovarian organ culture. Treatment of mice with 100 mg/kg 2-DG resulted in a 2.6
      fold induction of Foxo3 in the ovary and a 58% decrease in type 3a primary
      follicles. CONCLUSION(S): Expression of Foxo3 is induced by nutrient deprivation
      in cell culture, organ culture, and in vivo. In mice, 2-DG treatment results in
      an inhibition of primordial follicle activation. These data indicate that Foxo3
      induction by 2-DG may be useful for fertility preservation.

PMID- 24559723
TI  - Comparing indicators of health and development of singleton young adults
      conceived with and without assisted reproductive technology.
AB  - OBJECTIVE: To compare outcomes for young adults conceived by assisted
      reproductive technology (ART) with non-ART-conceived young adults. DESIGN: Cohort
      study. SETTING: Not applicable. PARTICIPANT(S): Mothers and their offspring (aged
      18-28 years) conceived by ART; mothers and their non-ART-conceived offspring,
      randomly selected from the same source population. INTERVENTION(S): Structured
      telephone interviews, one with mothers and another with their young adult
      offspring. MAIN OUTCOME MEASURE(S): Maternal report on young adult offspring
      hospitalizations and chronic illness accumulated over the first 18 years of their
      lives; young adult self-report on perceived current quality of life, body mass
      index, pubertal development, and educational achievement. RESULT(S): Of 1,480
      eligible ART mothers, 80% were traced and contacted. Of those, 656 (55%)
      participated, reporting on 705 ART-conceived offspring; 269 (23%) declined
      participation and 262 (22%) did not respond. Of the participants, 84% consented
      to contact with their young adult offspring, of whom 547 (92%) participated.
      Random-digit dialing recruited 868 non-ART mothers and 549 offspring. Compared
      with non-ART young adults, the ART group had significant increases in three
      maternally reported outcomes: 1) hospital admissions, including those in the
      secondary school years; 2) atopic respiratory conditions; and 3) combined
      endocrine, nutritional, and metabolic disease ICD-10 category. Young adult
      reported outcomes were similar for both groups. CONCLUSION(S): This study
      addresses gaps in knowledge of outcomes beyond adolescence for those conceived by
      ART. Results show few adverse outcomes in this large cohort of young adults, but
      additional assessment through clinical review is required to address issues
      unable to be examined in this study.

PMID- 24559724
TI  - Association of cystic fibrosis transmembrane-conductance regulator gene mutation
      with negative outcome of intracytoplasmic sperm injection pregnancy in cases of
      congenital bilateral absence of vas deferens.
AB  - OBJECTIVE: To evaluate intracytoplasmic sperm injection (ICSI) results with
      regard to congenital bilateral absence of vas deferens (CBAVD) versus non-CBAVD
      obstruction, cystic fibrosis transmembrane-conductance regulator (CFTR) mutations
      versus non-CFTR mutations, and miscarriages or stillbirths versus live births per
      embryo transferred. DESIGN: Retrospective study with detailed chart review.
      SETTING: Center for reproductive medicine. PATIENT(S): Nine hundred forty-five
      men with obstructive azoospermia. INTERVENTION(S): One thousand four hundred
      fourteen ICSI cycles classified as CBAVD versus non-CBAVD obstruction, CFTR
      mutations versus non-CFTR mutations, and miscarriages/stillbirths versus live
      births per embryo transferred. MAIN OUTCOME MEASURE(S): Frequency of CFTR
      mutations and rates of fertilization, good embryos, clinical pregnancy,
      miscarriages and stillbirths, ectopic pregnancy, and live births. RESULT(S): CFTR
      mutations were more prevalent in men with CBAVD than in those with non-CBAVD
      obstruction. The rate of miscarriages and stillbirths per embryo transferred was
      higher in men with CBAVD than in those with non-CBAVD obstruction, whereas the
      rate of live births per embryo transferred was lower in men with CBAVD than in
      those with non-CBAVD obstruction. The rate of miscarriages and stillbirths per
      embryo transferred was higher in men with CFTR mutations than in those with non
      CFTR mutations. The frequency of CFTR mutations was higher in patients who
      experienced miscarriages/stillbirths than in those with live births.
      CONCLUSION(S): The frequency of CFTR mutations was higher in cases of CBAVD
      versus non-CBAVD obstruction. Possibly as a result of CFTR mutations, patients
      with CBAVD had a significantly increased risk of miscarriage and stillbirth and a
      reduced rate of live birth compared with patients with non-CBAVD.

PMID- 24559725
TI  - A longitudinal cohort study of intelligence and later hospitalisation with mental
      disorder.
AB  - OBJECTIVE: Few studies on the associations between pre-morbid IQ and mental
      disorders are based on comprehensive assessment of intelligence in both women and
      men and include a wide range of confounding variables. Thus, the objective of the
      present study was to examine the association between pre-morbid IQ and
      hospitalisation with any mental disorder, including possible gender differences
      in the association. METHODS: The study population was born in 1959-61 and
      premorbid IQ was assessed with the WAIS between 1982 and 1994. Information on
      mental disorders was obtained from Danish hospital registers with a mean follow
      up interval of 21.1years. A total of 1106 participants were analysed. RESULTS:
      Those with a mental disorder had a significantly lower mean pre-morbid IQ score
      than those without. For women, the adjusted IQ difference was 8.5 points, and for
      men it was 5.1 points. A decrease of one standard deviation in pre-morbid IQ was
      associated with 83% greater risk of developing a mental disorder among women
      (HR=1.83, 95% CI: 1.41-2.36), and 36% among men (HR=1.36, 95% CI: 1.07-1.73). The
      interaction between gender and IQ was not statistically significant. Associations
      did not differ noteworthy between verbal and non-verbal IQ. CONCLUSIONS: Pre
      morbid IQ was found to be significantly associated with the development of mental
      disorder.

PMID- 24559726
TI  - Children of terrorism survivors: physiological reactions seven years following a
      terrorist incident.
AB  - OBJECTIVE: The aim of this study was to examine psychiatric illness and
      physiological indicators in the children of Oklahoma City bombing survivors seven
      years after the event. METHODS: A study of 17 Oklahoma City bombing survivors and
      their 21 adolescent and young-adult children conducted seven years after the
      disaster used structured diagnostic interviews to examine psychiatric outcomes.
      Physiological measurements included heart rate, systolic blood pressure,
      diastolic blood pressure, and physiological reactivity measured in response to a
      semi-structured bombing-reminder interview. RESULTS: Results revealed a
      statistically significant positive association between survivors and their
      children with respect to both post-disaster and current posttraumatic stress
      disorder (PTSD). Also, children whose parents met diagnostic criteria for either
      post-disaster or current major depression were more likely to meet criteria for a
      post-disaster behavior disorder and for any post-disaster psychiatric disorder
      than children whose parents did not meet criteria for post-disaster or current
      major depression. Survivors' children meeting criteria for any post-disaster
      psychiatric diagnosis had higher heart rates during the pre-test, test, and post
      test periods than children who did not meet criteria for any disorder. Children
      whose survivor parents met criteria for bombing-related PTSD and for any post
      disaster psychiatric disorder had greater heart rate reactivity than those whose
      parents did not. CONCLUSION: Findings of this study support previous literature
      on the relationships between children's psychiatric illness and physiological
      reactions and suggest interactions between disaster survivors' psychiatric
      illness and their children's psychiatric and physiological status.

PMID- 24559727
TI  - The human placenta expresses multiple glucocorticoid receptor isoforms that are
      altered by fetal sex, growth restriction and maternal asthma.
AB  - INTRODUCTION: We have previously identified sex-specific differences in the fetal
      placental response to cortisol. Our recent studies suggest that this differential
      response to cortisol is driven by differences in glucocorticoid receptor (GR)
      protein function rather than through changes in gene transcription or protein
      expression. METHODS: This study was designed to define whether the human placenta
      expresses different isoforms of the GR and whether expression was altered by
      fetal sex and maternal asthma. Asthma and non-asthma pregnant women were
      prospectively recruited at their first antenatal visit and placentae collected at
      delivery. Placental GR expression was examined in relation to maternal asthma,
      fetal sex and birthweight. RESULTS: Twelve specific bands for the GR were
      identified at molecular weights of 94, 91, 81, 74, 69, 68, 65, 60, 55, 50, 48 and
      38 kDa. The 12 isoforms were localised to the placental trophoblast and
      expression varied in relation to cellular location in either the cytoplasm or
      nucleus, fetal sex, fetal size and the presence and absence of maternal asthma.
      CONCLUSION: This is the first study to identify the presence of several protein
      isoforms of the GR in the human placenta. The data suggest glucocorticoid
      resistance observed in male placentae may be mediated through increased GRbeta,
      GR A and GR P localisation to the nucleus. While female placentae may be more
      sensitive to cortisol in the presence of maternal asthma through a decrease in
      GRbeta and an enhancement GRalpha activity via an interaction with GRalpha D3 and
      GRalpha C.

PMID- 24559728
TI  - Effect of holding of semen and washing of seminal plasma on quality and fertility
      of Hampshire boar semen preserved at liquid state.
AB  - The present study was aimed to reveal the effect on keeping quality of boar semen
      on holding or not holding at an elevated temperature than that used for
      preservation when combined with washing or not washing of seminal plasma. Twenty
      ejaculates, four from each of five Hampshire boars were used to hold for 0 and 4h
      in GEPS extender at 22 degrees C and subsequently washed (1500*g for 10min) of
      seminal plasma or left unwashed and preserved at 15 degrees C for 72h after
      extending with the same extender. The seminal parameters in terms of sperm
      motility, live spermatozoa, and live spermatozoa with intact acrosome (LIA) were
      evaluated at 0h-(immediately after extension) and thereafter at 24h intervals.
      The mean percentage of sperm motility was significantly (P<0.01) higher in
      unwashed than washed semen at both 0h and 4h of holding irrespective of
      preservation period. It was significantly (P<0.01) higher in semen held for 4h
      than 0h irrespective of washing and significantly (P<0.01) lower in washed than
      in unwashed semen irrespective of holding during preservation. Irrespective of
      preservation period the mean percentage of live spermatozoa was significantly
      (P<0.01) higher with 4h than 0h of holding in both unwashed and washed semen and
      was significantly (P<0.01) higher in unwashed than washed semen at both 0h and 4h
      of holding. It was significantly (P<0.01) higher for 4h held semen irrespective
      of washing and was significantly (P<0.01) lower in washed than in unwashed semen
      irrespective of holding during preservation. The mean percentage of LIA was
      significantly (P<0.01) higher with 4h than with 0h holding in both unwashed and
      washed semen and was significantly (P<0.01) higher in unwashed than in washed
      semen at both 0h and 4h of holding irrespective of preservation period. It was
      significantly (P<0.01) higher for 4h held as compared to unheld semen
      irrespective of washing and was significantly (P<0.01) lower in washed than
      unwashed semen irrespective of holding during preservation. The mean percentage
      of sperm motility, live spermatozoa and LIA decreased significantly (P<0.01) in
      0h and 4h holding irrespective of washing and in unwashed and washed semen
      irrespective of holding with increase in preservation period. Among all the
      treatments unwashed semen held for 4h yielded superior sperm quality on
      preservation. A total of 32 female pigs were inseminated using preserved semen
      obtained with the best processing technique found in the study. The conception
      rate, farrowing rate and litter size at birth were recorded to be 81.25%, 78.13%
      and 7.96 respectively as compared to 73.38%, 67.57% and 6.68 respectively in the
      control group. It could be concluded that unwashed Hampshire boar semen held for
      4h, extended with GEPS and preserved at 15 degrees C for 72h was conducive to
      obtain optimum fertility and fecundity in females when used for artificial
      insemination. 

PMID- 24559729
TI  - [Evolution of the use of antidepressants, anxiolytics and hypnotics in Valencia.
      Period 2000-2010].
AB  - OBJECTIVE: To describe the evolution in the use of antidepressants (AD),
      anxiolytics (A) and hypnotics (H) in the Comunitat Valenciana (CV) between 2000
      and 2010, their expenditure, and the cost of the defined daily dose (DDD).
      DESIGN: Retrospective observational study. SETTING: Prescriptions covered by the
      health public service of the CV during the period 2000-2010. MEASUREMENTS:
      Consumption of the therapeutic groups N06A (antidepressants), N05B (anxiolytics)
      and N05C (hypnotics) from the pharmacy database of the public Valencian Health
      Agency measured in defined daily dose per 1.000 inhabitants. RESULTS: During the
      period of study the use of AD increased by 81.2% and A and H, 11.7%. Selective
      serotonin reuptake inhibitors were the most prescribed AD and Selective serotonin
      and norepinephrine reuptake inhibitors experienced the higher rise (386.8%). The
      increase of escitalopram was 1.013%. Lorazepam, alprazolam and diazepam,
      accounted for the 80.4% of the anxyolitics, and lormetazepam and zolpidem the
      88.7% of the hypnotics. The expenditure rise of AD was by 78.2% and that of the A
      and H was 14.5%; the cost of the DDD of both decreased by 29%. CONCLUSIONS:
      Antidepressant utilization has experienced a remarkable rise between 2000 and
      2010 while that of A and H has been mild even though they are still more consumed
      than AD. In spite of the reduction of the DDD cost in both therapeutic groups,
      the whole expenditure on AD in the CV is still growing.

PMID- 24559730
TI  - Mastopexy sutures masquerading as an organic breast lesion on MRI scan.

PMID- 24559731
TI  - Bilobed flap for web reconstruction in adult syndactyly release: a new technique
      that can avoid the use of skin graft.
AB  - AIM: The aim of the study was to describe the use of a bilobed flap for web
      formation of syndactyly release, which decreases the need for graft and also
      avoids the use of skin grafting in syndactyly cases. METHODS: A retrospective
      review of this procedure was performed for 15 web space reconstructions. Patients
      were aged 20-23 years. The mean follow-up period was 7-12 months (mean 7 + 3.2).
      The operations were performed for the beneficial use of the dorsal hand skin by
      lowering the need for a skin graft. The flap was on the dorsum of the hand and
      proximal phalanx and was used for web formation. RESULTS: Surgery was completed
      without skin grafting in nine cases of 14 web spaces; two of them were
      complex/complete syndactylies, and two of them were simple/complete syndactylies.
      We used a skin graft in one patient because of triangular flap necrosis in a
      second operation. The use of a bilobed flap allowed the construction of web
      spaces, providing satisfactory cosmetic outcomes. No partial necrosis or
      complications was observed in bilobed flaps. No secondary correction was needed
      during the follow-up period. CONCLUSION: The present surgical technique could be
      a new surgical option for web formation and reconstruction in primary and
      secondary cases, especially in an adult population in which the skin on the
      dorsum of the hand is more pliable. LEVEL OF EVIDENCE: IV.

PMID- 24559732
TI  - Diagnostic challenges of assessing the depth of burn injuries overlying intricate
      coloured tattoos.

PMID- 24559733
TI  - Successful delayed nose replantation following a dogbite: arterial and venous
      microanastomosis using interpositional vein grafts.
AB  - The nose is one of the most important aesthetic units of the face. Following
      traumatic amputation, although technically very challenging, replantation is
      undoubtedly the procedure of choice. We present the first successful replantation
      of a partially amputated nose subjected to an ischaemic time of over 12 h. The
      injury was sustained following a dog-bite and inter-positional vein grafts were
      used to re-establish both arterial and venous blood flow. 

PMID- 24559734
TI  - Pellicle of thermotolerant Acetobacter pasteurianus strains: characterization of
      the polysaccharides and of the induction patterns.
AB  - Acetobacter species are well known to have the ability to grow floating on the
      surface of the medium by producing pellicle, which consists of cells and a self
      produced matrix of cell-attached polysaccharide. We previously isolated three
      thermotolerant strains (SL13E-2, SL13E-3, and SL13E-4) from Sri Lankan coconut
      vinegar and identified all these strains as Acetobacter pasteurianus. The
      pellicle polysaccharides of these three strains and of A. pasteurianus SKU1108,
      which was originally isolated from Thailand, were characterized. The
      monosaccharide composition of the pellicle polysaccharides of these A.
      pasteurianus strains was found to be varied. For example, the pellicle
      polysaccharide of SL13E-2 is composed of rhamnose and glucose in the ratio 1:8,
      and that of SL13E-4 and mesophilic A. pasteurianus NBRC3191 consists of rhamnose,
      glucose and xylose in the ratio 1:5:2 and 1:4:2, respectively. On the other hand,
      the pellicle polysaccharides of SL13E-3 and SKU1108 strains are composed of
      rhamnose, glucose and galactose in the ratio 2:2:1 and 1:5:2.5, respectively. The
      pellicle formation of thermotolerant SL13E-2, SL13E-3, and SL13E-4 was found to
      be significantly induced by the addition of ethanol, while poor induction was
      observed with SKU1108. The size and sugar composition of the polysaccharides
      obtained from cells induced by ethanol and by uninduced cells were the same,
      indicating that the number of molecules of the polysaccharides had increased but
      the polysaccharide molecule remained unchanged. The addition of a sugar source
      such as glucose, sucrose or fructose slightly induced pellicle formation in
      SKU1108, especially at 40 degrees C.

PMID- 24559735
TI  - A decadal prediction of the quantity of plastic marine debris littered on beaches
      of the East Asian marginal seas.
AB  - Large quantities of plastic litter are expected to wash ashore along the beaches
      of the East Asian marginal seas in the coming decade. Litter quantities were
      predicted using three techniques: a particle tracking model (PTM) used in
      conjunction with two-way PTM experiments designed to reveal litter sources, an
      inverse method used to compute litter outflows at each source, and a sequential
      monitoring system designed to monitor existing beach litter using webcams.
      Modeled year-to-year variation in litter quantities indicated that the amount of
      litter would continue to increase in the East Asian marginal seas if the level of
      outflow remains constant in the coming decade. The study confirms that about 3%
      of all East Asian beaches may potentially experience a 250-fold increase in the
      amount of plastic beach litter washed ashore in the next 10 years.

PMID- 24559736
TI  - Comparative embryotoxicity of phenanthrene and alkyl-phenanthrene to marine
      medaka (Oryzias melastigma).
AB  - Alkylated polycyclic aromatic hydrocarbons (alkyl-PAHs) are the predominant form
      of PAHs in oil, comprising 85-95% of total PAHs. However, little attention has
      been paid to these chemicals in ecological risk assessment of marine oil spill. A
      comparative study of the toxic effects of phenanthrene and retene (7-isopropyl-1
      methylphenanthrene, an alkyl-phenanthrene) on the early life stage of marine
      medaka (Oryzias melastigma) was conducted. Results showed that retene was
      significantly more toxic than phenanthrene, and marine medaka could be more
      sensitive to retene than some freshwater fishes. Retene had a higher excretion
      rate than phenanthrene during the larvae stage. Both of compounds resulted in
      developmental malformation of marine medaka embryos, with phenanthrene affecting
      on peripheral vascular system and yolk sac, while retene affecting on cardiac
      tissues. The toxicity of phenanthrene might be mainly related to its anesthetic
      effects, and that of retene might be related to the CYP1A-mediated toxicity of
      its metabolites. 

PMID- 24559737
TI  - Tropical islands quick data gap analysis guided by coral reef geomorphological
      maps.
AB  - A gap analysis is the initial step towards the identification of areas where data
      are needed. However, often, data coverage cannot be assessed against a reference
      that objectively guides the identification of both gaps and priority areas for
      data acquisition. Here, we describe a quick, effective and reproducible spatial
      data gap analysis approach based on the relationship between location of
      available metadata and coral reef geomorphological richness. In Solomon Islands,
      we identified gaps defined by high richness and low biological data coverage. We
      collected metadata only, to avoid dealing with data ownership, availability, and
      formats, and to be able to identify gaps in less than two months. This fast
      method does not replace quantitative and comprehensive gap analysis, but provides
      effective identification of areas of high natural value and limited knowledge.
      The method is widely applicable and particularly invaluable for large and complex
      domains such as the Coral Triangle. 

PMID- 24559738
TI  - Influence of urban runoff, inappropriate waste disposal practices and World War
      II on the heavy metal status of sediments in the southern half of Saipan Lagoon,
      Saipan, CNMI.
AB  - Heavy metals were examined in sediments from the southern half of Saipan Lagoon.
      These waters provided tactical access for US troops during WWII and were heavily
      shelled at the time. Mercury profiles in sediments were, to some extent,
      reflective of this event. Samples from the southern end of the lagoon, where an
      old post-war dumpsite once existed, were found to be substantially enriched with
      Pb, Cu and Zn. Further north, the lagoon was primarily impacted by urban runoff.
      Metal enrichment in sediments from this region was generally highest at storm
      drain outlets and attenuated seawards. Moderate enrichment was rarely exceeded
      for any element other than Hg beyond the 50 m mark. Sediment quality guidelines
      used to flag potentially adverse ecological health effects revealed no PEL
      exceedances. TEL exceedances for Pb and Cu were identified in sediments near the
      former dumpsite. The public health implications of the data are briefly
      addressed.

PMID- 24559739
TI  - A new magnetic expanded graphite for removal of oil leakage.
AB  - Magnetic expanded graphite (MEG) was prepared using the blended calcination
      method under a nitrogen atmosphere. MEG was characterized by scanning electron
      microscope (SEM), X-ray powder diffraction (XRD), Raman spectroscopy, and
      vibrating sample magnetization (VSM). Results show that the cobalt ferrite
      nanoparticles were uniformly and efficiently deposited on expanded graphite (EG).
      The saturation magnetization reached 55.05 emu g(-1), and the adsorption capacity
      of MEG under the optimal condition was 35.72 g g(-1) for crude oil.

PMID- 24559740
TI  - Total and organic mercury concentrations in the muscles of Pacific albacore
      (Thunnus alalunga) and bigeye tuna (Thunnus obesus).
AB  - Muscles of 115 North Pacific albacore (ALB, Thunnus alalunga) and 75 Pacific
      bigeye tuna (BET, Thunnus obesus), collected from 2001 to 2006, were analyzed. No
      ALB, but 13 large BET had organic mercury (OH g) concentrations exceeding 1 MUg
      g(-1) wet weight. For both ALB and BET, total mercury (THg) and OH g
      concentrations were significantly and positively correlated with fork length (FL)
      and body weight. The muscle Hg bioaccumulation rates of BET were higher than
      those of ALB, particularly in the adult fish. Moreover, the lines had crossover
      points among the two species that imply the young BET (FL<110 cm) contains lower
      muscle Hg concentrations than ALB of the same size. The suggested weekly dietary
      intake of ALB and small-BET meats is 340 g, and of BET meat it is 150 g for a 60
      kg person based on the provisional tolerable weekly intake (PTWI) of
      methylmercury set by the WHO.

PMID- 24559741
TI  - Rapidly progressive bilateral postmeningitic deafness in children: Diagnosis and
      management.
AB  - OBJECTIVES: To determine the diagnostic approach to severe or profound bilateral
      postmeningitic deafness and to propose management guidelines. MATERIAL AND
      METHODS: A retrospective review of five patients (two adolescents and three
      infants) with rapidly progressive severe bilateral deafness following an episode
      of meningitis managed between 2004 and 2010. RESULTS: The two adolescents
      presented Neisseria meningitidis meningitis and the three infants presented
      Streptococcus pneumoniae meningitis. Acquired bilateral deafness was diagnosed by
      audiometry an average of 68.8 days (range: 9-210) after the episode of
      meningitis. Behavioural audiological testing, adapted to age and state of health,
      was performed in all patients. Deafness was confirmed by Auditory Brainstem
      Response tests. All five patients were assessed by computed tomography (CT) and
      magnetic resonance imaging (MRI) within ten days. T2-weighted MRI sequences
      showed endolymph changes in four patients. CT scan demonstrated ossification in
      only one patient. Bilateral cochlear implant was performed in all patients, with
      complete electrode array insertion for eight implants and partial insertion for
      two implants (20 and 21 out of 22 electrodes inserted). Good results were
      obtained with cochlear implants in four cases. CONCLUSIONS: Bilateral deafness
      can occur immediately or several months after bacterial meningitis, regardless of
      the micro-organism responsible, justifying screening by behavioural audiological
      testing adapted to age for two years following bacterial meningitis. Auditory
      Brainstem Response testing can confirm audiometric findings. When severe or
      profound bilateral deafness is observed, MRI must be performed urgently to detect
      endolymph inflammation or ossification. Early bilateral cochlear implantation is
      recommended in the presence of ossification.

PMID- 24559742
TI  - The enhancement of anaerobic biodegradability of waste activated sludge by
      surfactant mediated biological pretreatment.
AB  - In this study, the role of sodium dodecyl sulfate (SDS) was explored for the
      removal of extracellular polymeric substance (EPS) from waste activated sludge
      (WAS) followed by enzymatic bacterial pretreatment, which enhanced the subsequent
      anaerobic biodegradability. EPS was removed with 0.02 g/g SS of SDS. In the
      results of pretreatment, the suspended solids reduction and chemical oxygen
      demand solubilization were found to be 25.7% and 19.79% for deflocculated and
      bacterially pretreated sludge, whereas they were found to be 15.7% and 11% for
      flocculated sludge (without EPS removal and bacterially pretreated) and 7.85% and
      6% for control sludge (raw sludge), respectively. Upon examining the anaerobic
      biodegradability, the biogas yield potential of deflocculated and bacterially
      pretreated, flocculated, deflocculated alone, and control sludges were found to
      be 0.467 L/(g VS), 0.355 L/(g VS), 0.315 L/(g VS), and 0.212 L/(g VS),
      respectively. Thus, the deflocculation and bacterial pretreatment improved the
      anaerobic biodegradability efficiently.

PMID- 24559743
TI  - How to increase microbial degradation in constructed wetlands: influencing
      factors and improvement measures.
AB  - Microorganisms play a vital role in degradation of multiple pollutants in
      constructed wetlands (CWs). Thus, the search for methods to improve microbial
      degradation in CWs is crucial. This study provides a review of critical
      parameters including availability of organic carbon, redox condition,
      temperature, pH, presence of plants, media characteristics and their influences
      on microbial processes. Current strategies focusing on regulation of carbon
      source, redox condition, and choice of substrates to enhance microbial activity
      in CWs are also described. A special emphasis is given to the application of
      bioaugmentation to enhance microbial activities in wetland in future research. 

PMID- 24559744
TI  - Growth factor treated tensioned synoviocyte neotissues: towards meniscal
      bioscaffold tissue engineering.
AB  - Meniscal injury is a common cause of osteoarthritis, pain, and disability in dogs
      and humans, but tissue-engineered bioscaffolds could be a treatment option for
      meniscal deficiency. The objective of this study was to compare meniscus-like
      matrix histology, composition, and biomechanical properties of autologous
      tensioned synoviocyte neotissues (TSN) treated with fetal bovine serum (TSNfbs)
      or three chondrogenic growth factors (TSNgf). Fourth passage canine synoviocytes
      from 10 dogs were grown in hyperconfluent monolayer culture, formed into TSN, and
      then cultured for 3 weeks with 17.7% FBS or three human recombinant TSNgf (bFGF,
      TGF-beta1, and IGF-1). Cell viability was determined with laser microscopy.
      Histological architecture and the composition of fibrocartilage matrix were
      evaluated in TSN by staining tissues for glycosaminoglycan (GAG), alpha-smooth
      muscle actin, and collagen 1 and 2; quantifying the content of GAG, DNA, and
      hydroxyproline; and measuring the gene expression of collagens type 1alpha and
      2alpha, the GAG aggrecan, and transcription factor Sry-type Homeobox Protein-9
      (SOX9). Biomechanical properties were determined by materials testing force
      deformation curves. The TSN contained components and histological features of
      mensical fibrocartilage extracellular matrix. Growth factor-treated TSN had
      higher DNA content but lower cell viability than TSNfbs. TSNgf had greater
      fibrocartilage-like matrix content (collagen 2 and GAG content with increased
      collagen 2alpha and SOX9 gene expression). Additionally, TSNgf collagen was more
      organized histologically and so had greater tensile biomechanical properties. The
      results indicate the potential of TSN when cultured with growth factors as
      implantable bioscaffolds for the treatment of canine meniscal deficiency.

PMID- 24559745
TI  - What causes canine sino-nasal aspergillosis? A molecular approach to species
      identification.
AB  - On the basis of phenotypic identification methods, Aspergillus fumigatus is
      reported as the most commonly identified aetiological agent of canine sino-nasal
      aspergillosis (SNA). However, definitive identification of Aspergillus spp. using
      phenotypic features alone is unreliable. The aim of this study was to determine
      the molecular identities of fungal species causing SNA in dogs. Genomic DNA was
      extracted from 91 fungal isolates from 90 dogs diagnosed with SNA in Australia,
      the USA and Belgium, and the ITS1-5.8S-ITS2 ribosomal DNA and partial beta
      tubulin regions were sequenced. Eighty-eight of 91 (96.7%) isolates were
      identified as A. fumigatus and 3/91 (3.3%) belonged to Aspergillus section Nigri
      spp. (Aspergillus tubingensis: 2/91; Aspergillus uvarum: 1/91). These findings
      confirm that A. fumigatus is the most common aetiological agent of canine SNA.
      This is the first report to document a pathogenic role for A. tubingensis and A.
      uvarum in dogs.

PMID- 24559746
TI  - Formation of oxidized phosphatidylinositol and 12-oxo-phytodienoic acid
      containing acylated phosphatidylglycerol during the hypersensitive response in
      Arabidopsis.
AB  - Plant membranes are composed of a wide array of polar lipids. The functionality
      of these extends far beyond a pure structural role. Membrane lipids function as
      enzyme co-factors, establish organelle identity and as substrates for enzymes
      such as lipases and lipoxygenases. Enzymatic degradation or oxidation (enzymatic
      or non-enzymatic) of membrane lipids leads to the formation of a diverse group of
      bioactive compounds. Plant defense reactions provoked by pathogenic
      microorganisms are often associated with substantial modifications of the
      lipidome. In this study, we profiled changes in phospholipids during the
      hypersensitive response triggered by recognition of the bacterial effector
      protein AvrRpm1 in Arabidopsis thaliana. A simple and robust LC-MS based method
      for profiling plant lipids was designed to separate all the major species of
      glycerolipids extracted from Arabidopsis leaf tissue. The method efficiently
      separated several isobaric and near isobaric lipid species, which otherwise are
      difficult to quantify in direct infusion based profiling. In addition to the
      previously reported OPDA-containing galactolipids found to be induced during
      hypersensitive response in Arabidopsis, three OPDA-containing sulfoquinovosyl
      diacylglycerol species, one phosphatidylinositol species as well as two acylated
      OPDA-containing phosphatidylglycerol species were found to accumulate during the
      hypersensitive response in Arabidopsis. Our study confirms and extends on the
      notion that the hypersensitive response in Arabidopsis triggers a unique profile
      of Allene Oxide Synthase dependent oxidation of membrane lipids. Primary targets
      of this oxidation seem to be uncharged and anionic lipid species. 

PMID- 24559747
TI  - Preoperative evaluation of colorectal liver metastases: comparison of
      gadopentetate dimeglumine and gadoxetic-acid-enhanced 1.5-T MRI.
AB  - PURPOSE: The aim of this study was to compare the diagnostic performance of
      gadopentetate dimeglumine and gadoxetic-acid-enhanced MRI in patients with
      colorectal liver metastases. METHODS: Thirty patients were included and divided
      into three sets, as follows: gadopentetate dimeglumine set-hepatic arterial
      phase, portal venous phase, and delay phase; gadoxetic acid set-hepatic arterial
      phase, portal venous phase, and delay phase; combined set-gadoxetic acid set and
      hepatobiliary phase. The accuracy was assessed by the area under the alternative
      free response receiver operating characteristic curve; the sensitivity and
      positive predictive value were calculated. RESULTS: There were 81 colorectal
      liver metastases in all. Both readers noted higher diagnostic accuracies of the
      combined set than the other two sets. In the group of small lesions, both readers
      detected significantly higher sensitivities and positive predictive value on the
      combined set than the other two sets. CONCLUSIONS: The combined set showed higher
      accuracy and sensitivity, especially significantly higher accuracy and
      sensitivity on small lesions.

PMID- 24559748
TI  - The relationship between perimesencephalic subarachnoid hemorrhage and deep
      venous system drainage pattern and calibrations.
AB  - BACKGROUND AND PURPOSE: The purpose of this study is to investigate the
      relationship between Rosenthal basal vein (BVR) type and diameter and
      perimesencephalic nonaneurysmal subarachnoid hemorrhage (P-SAH). MATERIALS AND
      METHODS: Aneurysmal subarachnoid hemorrhage (A-SAH), P-SAH, and control groups
      were evaluated, and BVRs were classified by type. BVR diameters in patients were
      measured. RESULTS: There was a statistically significant difference of BVR
      drainage types between groups (P=.002). BVR diameters of patients with normal
      drainage pattern in P-SAH group were significantly smaller than those in both
      other groups (P<.001). CONCLUSION: There is a relationship between P-SAH and BVR
      primitive drainage type. P-SAH risk increases in parallel with decreasing caliber
      of BVR in patients with normal drainage pattern.

PMID- 24559749
TI  - Sonoelastography for the evaluation of an axillary schwannoma in a case of
      quadrilateral space syndrome.
AB  - Entrapment axillary neuropathy at the quadrilateral space, also known as
      quadrilateral space syndrome (QSS), is a rare cause of posterior shoulder pain.
      We present a case of an axillary schwannoma causing QSS evaluated by both
      conventional ultrasound and sonoelastography. The application of sonoelastography
      is useful in elaborating the elastic feature of a soft tissue tumor, which
      provides additional information to conventional ultrasound regarding its growth
      pattern, and can help the differential diagnosis and guide the management. 

PMID- 24559750
TI  - MRI of small intrahepatic mass-forming cholangiocarcinoma and atypical small
      hepatocellular carcinoma (<=3 cm) with cirrhosis and chronic viral hepatitis: a
      comparative study.
AB  - OBJECTIVE: The objective was to identify the decision-making magnetic resonance
      (MR) features in differentiating small intrahepatic mass-forming
      cholangiocarcinoma (sIMCC) from atypical small hepatocellular carcinoma (sHCC)
      (<=3 cm) in patients with cirrhosis and chronic viral hepatitis. METHODS: Signal
      features and relative contrast of sHCCs and sIMCCs in T2-weighted and dynamic
      enhanced imaging were analyzed. A subgroup comparison between the cirrhosis and
      noncirrhosis chronic viral hepatitis group was also made. RESULTS: Univariate
      analysis revealed that tumor contours (P<.001), signals in T2-weighted (P<.001)
      and each phase of contrast-enhanced scanning (P<.001), enhancement patterns
      (P<.001), as well as accompanying findings of tumor capsule (P<.001), hepatic
      capsule retraction (P<.001), bile duct dilation (P=.031), and transient hepatic
      intensity difference (P=.002) were different between sIMCC and atypical sHCC.
      Multivariate analysis indicated that dynamic enhancement patterns (P<.001) and
      signals in T2-weighted images (P=.024) were independent predictors for
      differentiation. Confusing MR features were more often observed in the cirrhosis
      group compared with those in the noncirrhosis chronic viral hepatitis group.
      CONCLUSION: Dynamic enhancement patterns and signals in T2-weighted images were
      the most important MR features to differentiate sIMCC from atypical sHCC with
      cirrhosis and chronic viral hepatitis.

PMID- 24559751
TI  - Assessment of liver fat in an obese patient population using noncontrast CT fat
      percent index.
AB  - OBJECTIVE: To develop a simplified method to quantify liver fat using computed
      tomography (CT) fat % index (CTFPI) compared to liver spleen method (CTL/S, CTL
      S). METHODS: Noncontrast CT of the liver was performed in 89 patients
      (overweight, obese, severely obese) to quantify fat, using the following:
      CTFPI=[(65-patient HU)/65]*100, normal live r=65 HU. RESULTS: There was a strong
      linear correlation between CTFPI and the standard method of assessing liver fat
      using CTL/S (r=-0.901), CTL-S (r=-0.911). Hepatic HU and CTFPI were significantly
      different in the severely obese group compared to other two groups (P<.05).
      CONCLUSION: Significant correlation indicates equal diagnostic accuracy of the
      two methods in appropriately calibrated scanners.

PMID- 24559752
TI  - Pseudo-hemothorax at computed tomography due to residual contrast media.
AB  - Pleural effusion is a clinical problem that has many causes, with hemothorax
      being one of them. Computed tomography readily characterizes pleural fluid with
      determination of the attenuation value, helping to distinguish hemothorax from
      other types of effusion. Herein, we report the case of a 67-year-old man with end
      stage renal disease in which a high-density pleural effusion due to residual
      contrast media was misinterpreted as hemothorax. Radiologists should consider the
      possibility of contrast media retention when interpreting a high-density pleural
      effusion in patients with end-stage renal disease. Recognition of this entity is
      crucial to avoid misdiagnosis, which might lead to unnecessary testing or
      procedures. 

PMID- 24559753
TI  - Assessment of an educational intervention on nurses' knowledge and retention of
      heart failure self-care principles and the Teach Back method.
AB  - BACKGROUND: Nurses must have optimum knowledge of heart failure self-care
      principles to adequately prepare patients for self-care at home. However, study
      findings demonstrate that nurses have knowledge deficits in self-care concepts
      for heart failure. METHODS: A quasi-experimental, repeated measures design was
      used to assess nurses' knowledge of heart failure self-care before, immediately
      after, and 3-months following an educational intervention, which also included
      the Teach Back method. Follow-up reinforcement was provided after the educational
      intervention. RESULTS: One hundred fifty nurses participated in the study.
      Significant differences were found between pre-test (65.1%) and post-test (80.6%)
      scores (p < 0.001). Teach Back proficiency was achieved by 98.3%. Only 61
      participants completed the 3-month assessment of knowledge. In this group, mean
      knowledge scores increased significantly across all three measurements (p <
      0.001): 66.5% (pre-test); 82.1% (post-test); 89.5% (follow up post-test).
      CONCLUSIONS: Participation in a comprehensive educational program resulted in
      increased nurses' knowledge of heart failure self-care principles and the
      knowledge was sustained and increased over time.

PMID- 24559755
TI  - Removal of plates and screws from the diaphyseal forearm.

PMID- 24559756
TI  - The effect of short arm cast length on forearm rotation.
AB  - PURPOSE: To compare ranges of active forearm pronation and supination with
      subjects wearing short arm casts of different lengths. MATERIALS AND METHODS:
      Forty right-handed healthy volunteers (20 men and 20 women) with an average age
      of 39 years (range, 26-58 y) were recruited. A goniometer with a circular plate
      and a handle connected to the scale indicator was used to measure forearm
      pronation and supination without a cast and with 3 different lengths of short arm
      cast. All casts extended from just proximal to the volar and dorsal aspects of
      metacarpophalangeal joints, and continued to either 2.5 cm distal to elbow
      flexion crease or 5 cm distal to the elbow flexion crease, or to the proximal one
      third position between the wrist flexion crease and the elbow flexion crease.
      RESULTS: Compared with no immobilization, the longest of the 3 constructs reduced
      active forearm rotation by 62%, whereas the cast to 5 cm from the elbow flexion
      crease reduced rotation to 50%, and the cast to the proximal one third of the way
      between the wrist and elbow flexion crease reduced rotation by 32%. Active
      forearm rotation was significantly dependent on cast length, and reductions in
      active forearm rotation were positively correlated with cast length. CONCLUSIONS:
      Limitation of active forearm rotation by a short arm cast is positively
      correlated with cast length. CLINICAL RELEVANCE: When a short arm cast is used to
      limit wrist motion and forearm rotation, it is better to extend it proximally but
      not to impinge on the antecubital fossa, where skin breakdown may occur.

PMID- 24559757
TI  - Computer-assisted navigation for dorsal percutaneous scaphoid screw placement: a
      cadaveric study.
AB  - PURPOSE: To investigate computer-assisted surgery (CAS) for dorsal insertion of
      percutaneous scaphoid screws and to compare operative time, accuracy, and
      fluoroscopy time with the traditional mini C-arm method. We hypothesized that CAS
      techniques would improve accuracy, reduce actual K-wire insertion time, and
      decrease fluoroscopy time. METHODS: Ten fresh cadaveric upper limbs were
      randomized to either CAS or traditional dorsal percutaneous scaphoid screw
      placement by a single surgeon. Custom orthoses were applied to the CAS arms
      followed by intraoperative computed tomography (CT) scan and navigation
      calibration. Time was recorded for the portion of setup that required surgeon
      input, ideal guide wire placement, and fluoroscopy. Postoperative CT scans of the
      CAS arms were obtained to confirm accuracy. Two-tailed unpaired Student t test
      was used to analyze the outcome variables. RESULTS: The CAS group required on
      average 4.8 +/- 0.8 minutes longer for setup. The time for placement of the
      guidewire in the ideal position was 4.6 +/- 1.5 minutes in the CAS group compared
      with 11.8 +/- 4.4 minutes in the control group. Fluoroscopy time was 18 +/- 4
      seconds for the CAS group and 114 +/- 38 seconds for the control group.
      Postoperative CT scans demonstrated 1.5 +/- 0.6 mm maximum deviation from the
      planned ideal screw. No significant differences were found in the accuracy
      between methods, the number of guidewire attempts, or the total surgical time.
      CONCLUSIONS: Computer-assisted surgery navigation of dorsal percutaneous scaphoid
      screw placement takes on average 5 minutes longer to set up, but leads to
      significantly reduced guidewire placement time and no differences in overall
      procedural time. This CAS method was as accurate as the traditional method and
      resulted in an approximate 6-fold reduction in fluoroscopy time. CLINICAL
      RELEVANCE: This is an effective imaging alternative to the mini C-arm for
      scaphoid fixation using existing intraoperative CT scanners and navigation
      software.

PMID- 24559754
TI  - Impact of tracheostomy placement on anxiety in mechanically ventilated adult ICU
      patients.
AB  - OBJECTIVE: To determine if self-reported anxiety levels decreased after
      tracheostomy placement in a sample of mechanically ventilated intensive care unit
      patients. BACKGROUND: There is limited research regarding the impact of a
      tracheostomy on patients' anxiety. Elevated anxiety delays healing and
      contributes to long-term mental health complications. METHODS: This was a
      secondary analysis of data from a large clinical trial conducted in urban
      Minnesota. Fifty-one of 116 patients received a tracheostomy. Anxiety scores were
      obtained daily using the Visual Analog Scale-Anxiety. Mixed model analysis was
      used to compare anxiety ratings pre- and post-tracheostomy. RESULTS: There was no
      significant decrease in anxiety following tracheostomy after controlling for time
      and gender (all p > .16). Age was the only variable to impact anxiety levels:
      anxiety scores increased as age increased (p = .02). CONCLUSIONS: Prospective
      studies are needed to more accurately assess the impact of tracheostomy placement
      on patient anxiety and salient outcomes.

PMID- 24559758
TI  - Biomechanical comparison of 3 methods of scapholunate ligament reconstruction.
AB  - PURPOSE: To compare the biomechanical characteristics of 3 methods of
      scapholunate (SL) ligament reconstruction, including 1 that provides a biological
      central axis tether. METHODS: Twelve fresh-frozen cadaver limbs were mounted on a
      jig that allowed for wrist and finger motion by tendon loading. The specimens
      were randomized to receive the SL axis method (SLAM) reconstruction, the Blatt
      capsulodesis (BC), or the modified Brunelli tenodesis (MBT). Fluoroscopic images
      were taken to measure the SL interval and SL angle in various positions. The
      specimens were evaluated in 4 states: intact, with the SL and radioscaphocapitate
      ligaments cut, after reconstruction, and after reconstruction followed by 100
      cycles of simulated motion. RESULTS: After cycling, the MBT and the SLAM
      reconstructions performed significantly better than the BC in recreating the
      intact SL interval in a clenched fist posture. The SLAM SL interval trended to be
      closer to the intact state than the MBT SL interval. The SLAM reconstruction also
      trended toward greater restoration of the native SL angle in the clenched fist
      posture than either the MBT or the BC. CONCLUSIONS: The SL ligament
      reconstruction that uses a 2-tailed tendon autograft placed along the axis of
      rotation of the SL joint and secured both at the scaphoid and the lunate
      minimized creep and reconstructed the critical dorsal SL ligament. The SLAM
      achieved improved the SL interval and SL angle correction compared with
      conventional techniques of SL ligament reconstruction. CLINICAL RELEVANCE: The
      SLAM method may be a useful alternative for SL ligament reconstruction.

PMID- 24559759
TI  - Rheumatoid nodules.

PMID- 24559760
TI  - Distal myasthenia gravis.

PMID- 24559761
TI  - [Medication reconciliation errors in patients with multiple diseases].

PMID- 24559763
TI  - Clinical Neuropathology practice news 2-2014: ATRX, a new candidate biomarker in
      gliomas.
AB  - Genome-wide molecular approaches have substantially elucidated molecular
      alterations and pathways involved in the oncogenesis of brain tumors. In gliomas,
      several molecular biomarkers including IDH mutation, 1p/19q co-deletion, and MGMT
      promotor methylation status have been introduced into neuropathological practice.
      Recently, mutations of the ATRX gene have been found in various subtypes and
      grades of gliomas and were shown to refine the prognosis of malignant gliomas in
      combination with IDH and 1p/19q status. Mutations of ATRX are associated with
      loss of nuclear ATRX protein expression, detectable by a commercially available
      antibody, thus turning ATRX into a promising prognostic candidate biomarker in
      the routine neuropathological setting. 

PMID- 24559764
TI  - Effects of intermittent suckling on body composition of Iberian piglets weaned at
      35 days of age.
AB  - Piglet body composition at weaning could be a determinant for pig's viability and
      may be influenced by factors such as the nutritional management followed during
      suckling. An experiment was conducted to study whether intermittent suckling (IS)
      affects body composition at weaning and nutrient and energy retention during a 34
      day lactation period in Iberian piglets. Litters were subjected to conventional
      suckling (CS) or IS (n=10 litters of six piglets per treatment) in two trials.
      All piglets had ad libitum access to creep feed from day 15 onwards. In IS,
      piglets were progressively separated from the sow for 6, 8 and 10 h daily during
      the last week of lactation, whereas in CS piglets had continuous access to their
      dams. Creep feed intake in litters and BW development of individual piglets were
      measured throughout the 34-day lactation. Within each litter, both at birth and
      at weaning (day 35), one piglet was used to assess nutrient retention and body
      composition by the comparative slaughter approach. During days 29 to 35 of the
      experiment, daily creep feed intake was greater in IS piglets (IS 124, CS 67
      g/piglet, P=0.040), and average daily gain differed significantly between groups
      (IS 190, CS 150 g/day, P=0.010). BW at weaning was higher in the IS than in the
      CS piglets (IS 8.19, CS 7.48 kg, P=0.011). Empty-body fat and energy content at
      weaning were higher in the IS compared with CS litters, as well as fat content in
      the carcass (P=0.04). The IS treatment did not affect empty-body protein
      deposition, but significantly increased daily retention of fat, energy, ash and
      calcium, compared with CS litters (P<0.05). Thus, IS in Iberian piglets seems to
      enhance feed intake, growth rate and retention of some body components, which may
      contribute to a higher body fat content at weaning and facilitate the weaning
      process. 

PMID- 24559765
TI  - Star Excursion Balance Test performance and application in elite junior rugby
      union players.
AB  - OBJECTIVES: To evaluate performance on selected reach directions of the Start
      Excursion Balance Test (SEBT) in an elite underage rugby union population, and
      determine if differences exist between the forward and back position units. This
      information may have implications for the application of this test in player
      injury prevention and management. DESIGN: Descriptive study. SETTING: Gymnasium
      at an elite junior rugby union screening camp. PARTICIPANTS: 102 healthy male
      elite rugby union players (age = 17.9 +/- 1.1 years, height = 1.83 +/- 0.07 m,
      body mass = 90.5 +/- 11.3 kg). MAIN OUTCOME MEASURES: Participants were assessed
      on the Anterior (A), Posterior-medial (PM), and Posterior-lateral (PL) reach
      directions of the SEBT. RESULTS: Normative data for SEBT performance in the A, PM
      and PL reach directions were established for an elite junior rugby union
      population. No significant differences in dynamic postural stability were
      observed between the forward and back position units. CONCLUSIONS: This study
      provides normative SEBT data on an elite junior rugby union population, which
      enables clinicians to compare player dynamic postural stability and has
      implications for use in the prevention and management of player injuries.

PMID- 24559767
TI  - [Effect of a physical activity programme in patients with fibromyalgia: a
      systematic review].
AB  - The aim of this review was to determine what type of physical activity programmes
      have been developed in patients with fibromyalgia and what are its effects and
      benefits on the degree of pain and quality of life. The search was performed in
      MEDLINE, Web of Science and SPORTDiscus databases. The word "fibromyalgia" was
      always used as a criterion for combined search (using "AND" connector) with
      physical activity, exercise, physical therapy and training (MeSH terms). Of the
      2,531 initial results, 33 papers were selected for review. The studies reviewed
      focus primarily on dance activities, water activities, multidisciplinary, mind
      body work, fitness and stretching. After applying the intervention program, the
      pain level was reduced between 10 and 44.2%, and the impact of the disease
      between 5.3 and 17.9%, improving the symptoms of these patients. In conclusion, a
      multidisciplinary programme (in which physical activity is included) may have
      positive effects on the quality of life of people with fibromyalgia.

PMID- 24559766
TI  - Sustained response with gemcitabine plus Nab-paclitaxel after folfirinox failure
      in metastatic pancreatic cancer: report of an effective new strategy.
AB  - INTRODUCTION: Folfirinox has shown a benefit in terms of survival and quality of
      life in first line treatment of metastatic pancreatic cancer. However, efficacy
      of second line chemotherapy after folfirinox is still limited. Gemcitabine plus
      Nab-paclitaxel have been recently validated as first line treatment with an
      increased overall survival compared to gemcitabine. This combination has never
      been studied as second-line after folfirinox. CASE REPORT: A metastatic
      pancreatic cancer was diagnosed in a 60-year-old patient with a performance
      status of 0. After 10 cycles of folfirinox, and an initial objective response, we
      objectively noted progressive disease according to the RECIST 1.1 criteria
      together with an increased carbohydrate antigen 19-9. The multidisciplinary team
      decided to use gemcitabine plus Nab-paclitaxel as second line palliative
      chemotherapy. After 2 months, we obtained an objective response. After 6 months,
      this response was maintained with an acceptable tolerability. CONCLUSION:
      Gemcitabine plus Nab-paclitaxel, as second line palliative chemotherapy, after
      failure of folfirinox, could be a good strategy for patients with a performance
      status of 0 and 1. Obviously, this data has to be confirmed in larger patients
      series and in future comparative clinical studies.

PMID- 24559768
TI  - Development of tag-free photoprobes for studies aimed at identifying the target
      of novel Group A Streptococcus antivirulence agents.
AB  - We previously reported the identification and development of novel inhibitors of
      streptokinase (SK) expression by Group A Streptococcus (GAS), originating from a
      high throughput cell-based phenotypic screen. Although phenotypic screening is
      well-suited to identifying compounds that exert desired biological effects in
      potentially novel ways, it requires follow-up experiments to determine the
      macromolecular target(s) of active compounds. We therefore designed and
      synthesized several classes of chemical probes for target identification studies,
      guided by previously established structure-activity relationships. The probes
      were designed to first irreversibly photolabel target proteins in the intact
      bacteria, followed by cell lysis and click ligation with fluorescent tags to
      allow for visualization on SDS-PAGE gels. This stepwise, 'tag-free' approach
      allows for a significant reduction in molecular weight and polar surface area
      compared to full-length fluorescent or biotinylated probes, potentially enhancing
      membrane permeability and the maintenance of activity. Of the seven probes
      produced, the three most biologically active were employed in preliminary target
      identification trials. Despite the potent activity of these probes, specific
      labeling events were not conclusively observed due to a considerable degree of
      nonspecific protein binding. Nevertheless, the successful synthesis of potent
      biologically active probe molecules will serve as a starting point for initiating
      more sensitive methods of probe-based target identification. 

PMID- 24559769
TI  - Trends in prevalence of diabetes mellitus and mean fasting glucose in Portugal
      (1987-2009): a systematic review.
AB  - OBJECTIVES: To assess time trends of the prevalence of diabetes and mean blood
      glucose in Portuguese adults. STUDY DESIGN: Systematic review. METHODS: The
      search strategy included Pubmed search and screening of bibliographic references
      of the review articles. Sex-specific linear regression models, with survey year
      and participants' age as independent variables, were used to predict prevalence
      estimates of self-reported diabetes and mean fasting glucose. RESULTS: Twenty
      seven eligible studies were identified. Time trends of objectively defined
      diabetes could not be quantified due to the heterogeneity of the diagnostic
      criteria. Between 1987 and 2009, the prevalence of self-reported diabetes
      remained approximately constant in young adults, while it increased in middle
      aged and older adults, more than two-fold among women and three-fold among men.
      In the same period, mean fasting glucose increased 7 mg/dL among women and 8
      mg/dL among men. CONCLUSIONS: The prevalence of self-reported diabetes and mean
      fasting glucose increased in the last two decades, demanding for effective
      strategies to reverse this tendency and to manage the increasing number of people
      with diabetes in the Portuguese population.

PMID- 24559771
TI  - The cognitive models of limb apraxia and the specific properties of meaningful
      gestures.

PMID- 24559770
TI  - Economic burden of neural tube defects in Germany.
AB  - OBJECTIVE: Failure of closure of the neural tube often leads to serious
      malformations, including spina bifida, anencephaly and encephalocoele. Despite
      improvements in medical and surgical treatment, the burden associated with spina
      bifida is substantial but country-specific data are lacking outside North
      America. This study aims to improve understanding of the economic implications
      and burden associated with the morbidity of children and adults with neural tube
      defects (NTDs) in Germany. STUDY DESIGN: Retrospective data analysis. METHODS:
      2006-2009 German health insurance data of persons with NTDs (spina bifida and
      encephalocoele) were analysed to determine the economic burden of illness
      associated with NTDs in Germany. Cases were identified using ICD-10 codes; data
      included outpatient and inpatient care, rehabilitation, remedies and medical
      aids, pharmacotherapy use, long-term care and information on sick leave. The
      analysis was stratified by age group to provide a burden estimate specific to a
      person's age. To obtain an indicator of incremental burden to the Statutory
      Health Insurance (SHI), results were compared to the standardized healthcare
      expenditures according to the German Risk Compensation Scheme (RSA). RESULTS:
      Overall, 4141 persons with an ICD code related to NTDs were identified (out of a
      population of 7.28 million persons screened). The administrative prevalence
      ranged from 0.54 to 0.58 per 1000 enrollees. Of those, 3952 (95.4%) were
      diagnosed with spina bifida. The average annual mean healthcare expenditure of
      persons with spina bifida was ?4532 (95% CI = 4375-4689, SD = 9590, Median =
      1000), with inpatient care contributing ?1358 (30.0%), outpatient care ?644
      (14.2%), rehabilitation ?29 (0.6%), pharmacotherapy ?562 (12.4%), and remedies
      and medical aids ?1939 (42.8%). The incremental cost due to spina bifida was
      substantially higher than the standardized SHI expenditures for all age groups.
      The difference was highest for persons <= 10 years old (?10,971 vs ?2360 for the
      age group <= 1, ?8599 vs ?833 for the age group 2-5 years and ?10,601 vs ?863 for
      the age group 6-10 years). The difference was smallest for the age group 41-50
      years (?2524 vs ?1101) and for 71 years and over (?5278 vs ?4389). CONCLUSION:
      Expenditures of persons with spina bifida exceeded the standardized SHI
      expenditures, indicating a considerable economic burden. The economic burden is
      continuous throughout the person's life, with high monetary impact and exposure
      to the healthcare system (especially in early years of life). Efforts should be
      devoted to improve the prevention of NTDs and provide appropriate support for
      persons with NTDs, parents, and caregivers--especially in early years.

PMID- 24559772
TI  - [Treatment of hepatitis C with new direct antiviral drugs: towards a disease
      cure].

PMID- 24559773
TI  - Funded by the National Cancer Institute (NCI), the national oncology cooperative
      groups bring to the bedside the latest in evidence-based cancer treatment.
      Introduction.

PMID- 24559774
TI  - Nurse scientists in cancer cooperative groups.
AB  - OBJECTIVES: To review the significant advances in cancer prevention, detection,
      treatment, and symptom management among the National Cancer Institute (NCI)
      supported clinical trials cooperative groups, the Institute of Medicine (IOM)
      recommendations for restructuring of the national clinical trials infrastructure,
      and to discuss the contributions nurses have made in national clinical trials.
      DATA SOURCE: Published cooperative group manuscripts and NCI data. CONCLUSION:
      The NCI-sponsored clinical trials cooperative groups have conducted major
      evidence-based, practice-changing clinical trials. Despite the advances,
      challenges in the process of clinical trials have caused the NCI to restructure
      the clinical trials network to improve efficiencies and decrease time from
      concept to protocol development to clinical trials completion. IMPLICATIONS FOR
      NURSING PRACTICE: Nurse investigators work with the cooperative groups for a
      number of reasons, including access to a large multisite population of cancer
      patients, making findings more generalizable. There are also increasing
      opportunities for areas of research including biomechanistic understanding of
      symptoms and symptom therapies, survivorship, and cancer care delivery.

PMID- 24559775
TI  - The nurse liaison role in the cooperative group setting.
AB  - OBJECTIVES: To review the history of nurse involvement within the cooperative
      group environment, define the role of the nurse liaison, identify challenges for
      the nurse in interdisciplinary research, and explore future trends of nurse
      involvement in cooperative group studies. DATA SOURCES: Published articles,
      government reports, and Web sites. CONCLUSION: Nurse liaisons provide a nursing
      perspective to the design of cooperative group trials and ensure that nursing and
      patient feasibility issues about the trial are addressed, and provide guidance to
      nurses at participating institutions, as well as their home institution.
      IMPLICATIONS FOR NURSING PRACTICE: The nurse liaison must be committed to their
      cooperative group role. Because of their proximity in time and space to the
      patient, nurse liaisons have a unique vantage point that can provide meaningful
      feedback for all stages of protocol development, implementation, and evaluation.

PMID- 24559776
TI  - Children's Oncology Group nursing research framework.
AB  - OBJECTIVES: To describe the development and application of an organizing research
      framework to guide Children's Oncology Group (COG) nursing research. DATA
      SOURCES: Research articles, reports and meeting minutes. CONCLUSION: An
      organizing research framework helps to outline research focus and articulate the
      scientific knowledge being produced by nurses in the pediatric cooperative group.
      IMPLICATIONS FOR NURSING PRACTICE: The use of a COG nursing research organizing
      framework can facilitate the clinical nurse's understanding of how children and
      families sustain or regain optimal health when faced with a pediatric cancer
      diagnosis through interventions designed to promote individual and family
      resilience.

PMID- 24559777
TI  - Enhancing nurse contributions to SWOG clinical trials.
AB  - OBJECTIVES: To review nursing research contributions and future opportunities for
      nurses in cooperative oncology group research in SWOG (formerly Southwest
      Oncology Group). DATA SOURCES: Peer-reviewed journal articles, grant submissions,
      professional manuals, research policy reports, and meeting minutes. CONCLUSION:
      Nurses and nurse researchers have had active roles in SWOG research involving
      quality of life, symptom management, recruitment and adherence, and data quality.
      There are opportunities for nurses to make greater contributions to cooperative
      group research, particularly in cancer survivorship, health outcomes, and quality
      of life. IMPLICATIONS FOR NURSING PRACTICE: Nursing science and evidence-based
      practice will be enhanced by conducting nursing research in the multi-site
      cooperative group setting.

PMID- 24559778
TI  - Nursing's presence in the changing cooperative group setting.
AB  - OBJECTIVES: To describe the history of nurse-led contributions within three
      legacy cancer cooperative groups and the challenges and new opportunities faced
      by nurses with the merger of these three groups. DATA SOURCES: Journal articles,
      government and special health reports. CONCLUSION: Recent changes in the cancer
      cooperative group have significantly altered the way cancer clinical trials will
      be conducted in the future. With recent federal funding cuts, three cooperative
      groups have merged in an effort to improve efficiency, while maintaining the
      quality and availability of clinical trials for patients with cancer. The group
      merger presented a unique opportunity to maintain and advance nursing's
      contribution to education, research, and practice within the cooperative group
      setting. IMPLICATIONS FOR NURSING PRACTICE: As a result of merger, cooperative
      group nurses will expand their work to integrate oncology nursing practice within
      the alliance cooperative group's infrastructure, facilitating research and high
      quality patient care.

PMID- 24559779
TI  - Nursing contributions in Community Clinical Oncology Research Programs.
AB  - OBJECTIVES: To describe the Community Clinical Oncology Programs (CCOPs),
      identify the roles and functions of CCOP nurses in clinical trials, and discuss
      the future contributions of nurses in the National Cancer Institute (NCI)
      Community Oncology Research Program. DATA SOURCES: Research and review articles,
      Web sites, and government reports. CONCLUSION: The contribution of nurses in the
      community clinical research setting has not been defined or quantified; however,
      examination of the literature reveals substantial contributions from nurses in
      the conduct and dissemination of oncology research. IMPLICATIONS FOR NURSING
      PRACTICE: Nurses outside of academic settings must be as well versed in new
      research as those in large institutions. Education on clinical trials and
      oncology research is necessary in the treatment and care of cancer patients.
      Experienced community-based nurses are essential to the success of the NCI
      Community Oncology Research Program.

PMID- 24559780
TI  - Nursing research in the Gynecologic Oncology Group.
AB  - OBJECTIVES: To review nursing science history within the Gynecology Oncology
      Group (GOG); to discuss challenges of nursing science in the cooperative group
      (CG) using a current nurse-led protocol (GOG-0259) as an exemplar; and to propose
      recommendations to advance nursing science in the CG setting. DATA SOURCES:
      Indexed citations and personal experience. CONCLUSION: Benefits of CG research
      include opportunities for inter-disciplinary collaboration and ability to rapidly
      accrue large national samples. Challenges include limited resources to support
      non-treatment trials, a burdensome protocol approval process, and lack of
      experience with nursing/quality-of-life intervention studies. Formal GOG
      structures need to evolve to encourage nurse scientists to become active members;
      promote collaboration between experienced GOG advanced practice nurses and nurse
      scientists to identify nursing research priorities; and consider new funding
      sources to support pilot intervention studies. IMPLICATIONS FOR NURSING PRACTICE:
      Understanding the CG research process is critical for nurse scientists. A multi
      disciplinary team of CG leaders can help investigators navigate a complex
      research environment and increase awareness of the value of nursing research.

PMID- 24559781
TI  - A mentored cooperative group pilot study: atrophic vaginitis.
AB  - OBJECTIVES: To review nursing research initiatives from two cooperative groups
      and outline a pilot study performed by a junior nurse researcher mentored by
      cooperative group nurse researchers and institutional physicians. DATA SOURCES:
      PubMed, Cochrane Library, Scopus, World Wide Web. CONCLUSION: Nursing research
      can be initiated and led by nurses in the cooperative group setting. The team
      approach model of research includes several disciplines to examine multiple
      facets of the same problem, or of multiple problems that a cancer patient may
      face. This new model will enable a greater number of nurse researchers to
      investigate symptom management, survivorship, and quality-of-life issues.
      IMPLICATIONS FOR NURSING PRACTICE: Nurse researchers should be included in every
      cooperative group study to investigate nurse-sensitive outcomes and issues
      related to symptom management, survivorship, and quality of life.

PMID- 24559782
TI  - Public health and cooperative group partnership: a colorectal cancer
      intervention.
AB  - OBJECTIVES: To describe the development of a multi-component colorectal cancer
      educational tool for female breast cancer survivors through a cooperative group
      and public health partnership. DATA SOURCES: PubMed, World Wide Web, guidelines
      from professional organizations, surveys and focus groups with breast cancer
      survivors. CONCLUSION: Collaboration is at the core of cooperative group and
      public health research. This partnership led to the development of a colorectal
      cancer educational tool for breast cancer survivors. Focus groups revealed that
      female breast cancer survivors were receptive to education on colorectal cancer
      screening. IMPLICATIONS FOR NURSING PRACTICE: Nurses are instrumental in research
      collaborations between cooperative groups and public health. The colorectal
      educational intervention for breast cancer survivors serves as an exemplar of
      partnerships leading to innovative research planning and implementation outcomes.

PMID- 24559783
TI  - Methodological considerations in the design and implementation of clinical
      trials.
AB  - OBJECTIVES: To review study design issues related to clinical trials led by
      oncology nurses, with special attention to those conducted within the cooperative
      group setting; to emphasize the importance of the statistician's role in the
      process of clinical trials. DATA SOURCES: Studies available at clinicaltrials.gov
      using experimental designs that have been published in peer-reviewed journals;
      cooperative group trials are highlighted. CONCLUSION: The clinical trial is a
      primary means to test intervention efficacy. A properly designed and powered
      study with clear and measurable objectives is as important as the intervention
      itself. IMPLICATIONS FOR NURSING PRACTICE: Collaboration among the study team,
      including the statistician, is central in developing and conducting appropriately
      designed studies. For optimal results, collaboration is an ongoing process that
      should begin early on.

PMID- 24559784
TI  - EUS-FNA is superior to ERCP-based tissue sampling in suspected malignant biliary
      obstruction: results of a prospective, single-blind, comparative study.
AB  - BACKGROUND: Both EUS and ERCP sampling techniques may provide tissue diagnoses in
      suspected malignant biliary obstruction. However, there are scant data comparing
      these 2 methods. OBJECTIVE: To compare EUS-guided FNA (EUS-FNA) and ERCP tissue
      sampling for the diagnosis of malignant biliary obstruction. DESIGN: Prospective,
      comparative, single-blind study. SETTING: Tertiary center. PATIENTS: Fifty-one
      patients undergoing same-session EUS and ERCP for the evaluation of malignant
      biliary obstruction over a 1-year period. INTERVENTIONS: EUS-FNA and ERCP tissue
      sampling with biliary brush cytology and intraductal forceps biopsies. MAIN
      OUTCOME MEASUREMENTS: Diagnostic sensitivity and accuracy of each sampling method
      compared with final diagnoses. RESULTS: EUS-FNA was more sensitive and accurate
      than ERCP tissue sampling (P < .0001) in 51 patients with pancreatic cancers (n =
      34), bile duct cancers (n = 14), and benign biliary strictures (n = 3). The
      overall sensitivity and accuracy were 94% and 94% for EUS-FNA, and 50% and 53%
      for ERCP sampling, respectively. EUS-FNA was superior to ERCP tissue sampling for
      pancreatic masses (sensitivity, 100% vs 38%; P < .0001) and seemed comparable for
      biliary masses (79% sensitivity for both) and indeterminate strictures
      (sensitivity, 80% vs 67%). LIMITATIONS: Single-center study. CONCLUSION: EUS-FNA
      is superior to ERCP tissue sampling in evaluating suspected malignant biliary
      obstruction, particularly for pancreatic masses. EUS-FNA appears similar to ERCP
      sampling for biliary tumors and indeterminate strictures. Given the superior
      performance characteristics of EUS-FNA and the higher incidence of pancreatic
      cancer compared with cholangiocarcinoma, EUS-FNA should be performed before ERCP
      in all patients with suspected malignant biliary obstruction. ( CLINICAL TRIAL
      REGISTRATION NUMBER: NCT01356030.).

PMID- 24559785
TI  - Endovascular treatment for symptomatic iliac vein compression syndrome: a
      prospective consecutive series of 48 patients.
AB  - BACKGROUND: We sought to assess the prevalence of iliac vein compression syndrome
      (IVCS) in patients with unilateral left lower limb chronic venous disease and
      evaluate the feasibility and effectiveness of endovascular treatment for IVCS.
      METHODS: We conducted a prospective cohort study of 48 consecutive patients
      diagnosed with IVCS between December 2008 and May 2012. We divided the patients
      into 2 groups: thrombotic IVCS (n = 12) and nonthrombotic IVCS (n = 36). We
      evaluated the perioperative, 30-day, and 1-year outcomes of endovascular
      treatment. We estimated the stent patency rate using the Kaplan-Meier method.
      RESULTS: The prevalence of IVCS within our cohort was 14.8% (48/324). The
      technical success rate of the endovascular treatment was 95.8%. There was no
      death, pulmonary embolism, or contrast-induced nephropathy among the patients.
      The 1-year primary patency rate was 93.0%. There was no significant difference
      between the thrombotic and nonthrombotic IVCS groups (P = 0.156). Perioperative
      complications were minor and improved quickly. The median pain level recorded on
      a visual analogue scale declined from 4.5 to 1.2 (P < 0.05) in the thrombotic
      ICVS group and from 3.3 to 0.3 (P < 0.05) in the nonthrombotic ICVS group. The
      edema relief rates in the thrombotic and nonthrombotic ICVS groups were 81.8% and
      58.5%, respectively. The cumulative recurrence free ulcer healing rate was 71.4%
      12 months after treatment. CONCLUSIONS: IVCS is more common than previously
      thought among patients with unilateral left lower limb chronic venous disease.
      Endovascular therapy, a minimally invasive approach to treating venous lesions,
      is a feasible and effective treatment for left-sided IVCS and has a high
      technical success rate and an acceptable complication profile.

PMID- 24559786
TI  - Prognostic significance of an elevated neutrophil-lymphocyte ratio in the
      amputation-free survival of patients with chronic critical limb ischemia.
AB  - BACKGROUND: The aim of this study was to investigate the utility of admission
      neutrophil-lymphocyte ratio (NLR) in predicting the amputation-free survival
      (AFS) of patients with critical limb ischemia (CLI) who underwent an elective
      infrainguinal therapeutic intervention. METHODS: All patients with CLI undergoing
      elective infrainguinal vascular surgery (open or endovascular) at a single
      university teaching hospital between January 2005 and December 2009 were
      retrospectively identified from a prospectively maintained database. The primary
      end point was AFS. The cut-off of NLR >5 was used to categorize patients into low
      and high-NLR groups. Kaplan-Meier analysis and long-rank test were used to
      compare survival between both groups. Cox regression analysis was conducted to
      determine independent factors affecting the AFS. RESULTS: During a median follow
      up of 31 months, 561 patients with chronic CLI underwent infrainguinal
      revascularization. Five-year mortality was lower in the NLR <5 group (33%) than
      in the NLR >5 group (49%) (P <= 0.001), and the AFS was significantly higher in
      the NLR <5 group (50%) than in the NLR >5 group (26%) (P <= 0.001). In a
      multivariate analysis, preoperative NLR >5 was independently associated with 5
      year AFS (hazard ratio 2.325, 95% CI 1.732-3.121). CONCLUSIONS: Elevated NLR
      predicts a worse AFS in patients undergoing infrainguinal vascular
      revascularization with chronic CLI, suggesting that the NLR conveys powerful
      prognostic information that is independent of other conventional clinical risk
      factors.

PMID- 24559787
TI  - Iatrogenic May-Thurner syndrome after EVAR.
AB  - May-Thurner syndrome (MTS) is caused by compression of the left iliac vein
      between the right common iliac artery and the body of the fifth lumbar vertebra,
      resulting in hemodynamic compromise to venous return and intimal hyperplasia of
      the vein from chronic pulsatile compression. We report a case of MTS resulting
      from placement of an aortic stent graft for aneurysm repair. A higher index of
      suspicion and a more comprehensive initial venous duplex investigation, which
      should include the suprainguinal veins, should be considered in those patients
      with new onset of unilateral limb swelling after endovascular aneurysm repair
      (EVAR). 

PMID- 24559788
TI  - Preoperative infra- and suprarenal aortic pulsatile distension is comparable
      between relatively young and older patients with an abdominal aortic aneurysm.
AB  - BACKGROUND: Young healthy individuals have a large aortic pulsatile distension
      during the cardiac cycle. In patients with an abdominal aortic aneurysm (AAA),
      aortic distension during the cardiac cycle is associated with stent graft
      migration. However, whether the pulsatile distension is larger in relatively
      young patients with an AAA compared to older AAA patients is unknown. This study
      investigated whether preoperative pulsatile aneurysm neck distension is related
      to age. METHODS: From our database of endovascular aneurysm repair (EVAR), we
      selected 25 consecutive male patients <=65 years of age (group 1) and 25
      consecutive patients >65 years of age (group 2). All patients had a preoperative
      electrocardiogram-triggered computed tomography angiography scan consisting of 8
      phases. Aortic area and diameter changes per heartbeat were measured at 2 levels:
      (A) 3 cm above and (B) 1 cm below the most distal renal artery. RESULTS: In group
      1 compared to group 2, distension during the cardiac cycle at level A was 1.6 +/-
      0.4 versus 1.5 +/- 0.4 mm (P = 0.62), and the aortic area increase was 45.4 +/-
      19.6 versus 41.7 +/- 20.8 mm(2) (P = 0.52). Aortic distension at level B was 1.4
      +/- 0.3 versus 1.5 +/- 0.4 mm (P = 0.79), and the area increase was 35.5 +/- 12.0
      versus 35.0 +/- 15.5 mm(2) (P = 0.90). CONCLUSIONS: Preoperative pulsatile
      aneurysm neck distension did not differ between younger and older patients;
      therefore, we do not expect young patients to have more pulsatile distension
      related complications after EVAR.

PMID- 24559789
TI  - Validation of short screening tools for common mental disorders in Nigerian
      general practices.
AB  - OBJECTIVE: The objective was to examine the psychometric properties of two brief
      screening questionnaires for common mental disorders in general practices in
      areas speaking the three main Nigerian languages. METHOD: Consecutives attendees
      of selected general practices in Ibadan, Enugu and Kaduna were screened with the
      General Health Questionnaire 12-item version (GHQ12) and K6. We selected all
      cases and 50% of noncases for second-stage interview with the Composite
      International Diagnostic Interview. The receiver operating characteristic curves
      were generated for both questionnaires, and optimal cutoffs were determined.
      Exploratory factor analysis was done for both questionnaires. RESULTS: The K6 had
      an area under the curve (AUC) of 0.62 for depression and 0.58 for anxiety
      disorder. The GHQ12 had an AUC of 0.74 for depression, while that for generalized
      anxiety disorder was 0.6. The GHQ12 was able to correctly classify 75% of the
      subjects with or without depression, while the K6 was able to correctly classify
      56% of the subjects with or without depression. The optimal cutoff for both
      questionnaires was 4, selecting the point of best balance of sensitivity and
      specificity. CONCLUSION: The findings suggest that the GHQ12 will be a useful
      tool in screening for common mental disorders in general practice in Nigeria.

PMID- 24559790
TI  - Point prevalence and correlates of depression in a national community sample with
      multiple sclerosis.
AB  - OBJECTIVE: The prevalence of depression in multiple sclerosis (MS) is known to be
      elevated, but nearly all available studies have estimated period prevalence. The
      objective of this study was to estimate the point prevalence of depression in a
      representative community sample using the Patient Health Questionnaire, Brief
      (PHQ-9). METHODS: The data source for this study was the Survey of Living with
      Neurological Conditions in Canada, which was derived from a representative sample
      of household residents. RESULTS: The sample included 630 respondents with MS.
      With application of the standard PHQ-9 cut point (10+), the prevalence of
      depression was 26.0% (95% confidence interval 18.9%-33.0%). Depressed subjects
      had lower quality of life; an increased frequency of suicidal ideation; and more
      often reported a negative disease course, high stress, low social support and
      stigmatization. CONCLUSIONS: This study adds to the existing literature by
      providing point prevalence data: in any 2-week period, about one quarter of
      community residents with MS experience substantial levels of depressive symptoms.

PMID- 24559791
TI  - Catatonic episode after kidney transplantation.
AB  - There is a growing body of case reports of catatonic symptoms after organ
      transplantations. A considerable number of these cases might be attributed to
      neurotoxicity induced by immunosuppressive medications. However, the etiology of
      other cases remains unclear. We present the case of a 21-year-old woman who
      developed catatonia after kidney transplantation from a deceased donor. In this
      case, nontoxic tacrolimus levels were found, and other causal factors including
      infections, uremia or transplant rejection were excluded. Electroconvulsive
      therapy followed by olanzapine proved to be effective treatment. 

PMID- 24559792
TI  - Suicide attempts and mortality in eating disorders: a follow-up study of eating
      disorder patients.
AB  - OBJECTIVE: The aim of this study is to explore the prevalence of hospital-treated
      suicide attempts in a large clinical population of eating disorder patients.
      METHOD: Follow-up study of adults (N=2462, 95% women, age 18-62 years) admitted
      to the Eating Disorder Clinic of Helsinki University Central Hospital in the
      period 1995-2010. For each patient, four controls were selected and matched for
      age, sex and place of residence. The end point events were modeled using Cox's
      proportional hazard model, taking matching into account. RESULTS: We identified
      156 patients with eating disorder (6.3%) and 139 controls (1.4%) who had required
      hospital treatment for attempted suicide. Of them, 66 (42.3%) and 37 (26.6%) had
      more than one attempt. The rate ratio (RR) for suicide attempt in patients with
      eating disorder was 4.70 [95% confidence interval (CI) 1.41-15.74]. In anorexia
      nervosa, RR was 8.01 (95% CI 5.40-11.87), and in bulimia nervosa, it was 5.08
      (95% CI 3.46-7.42). In eating disorder patients with a history of suicide
      attempt, the risk of death from any cause was 12.8%, suicide being the main cause
      in 45% of the deaths. CONCLUSION: Suicide attempts and repeated attempts are
      common among patients with eating disorders. Suicidal ideation should be
      routinely assessed from patients with eating disorders.

PMID- 24559793
TI  - Implant time and process efficiency for CT-guided high-dose-rate brachytherapy
      for cervical cancer.
AB  - PURPOSE: This investigation details the time and teamwork required for CT-guided
      tandem and ring high-dose-rate brachytherapy. METHODS AND MATERIALS: From 2010 to
      2012, 217 consecutive implantations were identified on 52 patients. We gathered
      key workflow times: preoperative, applicator insertion, CT image, treatment
      planning, treatment, patient recovery, and total time in clinic. Linear fixed
      effects models were used, and key workflow times were the outcome variables and
      factors including age, body mass index, stage, outside referral, number of
      implant per patient, number of implants per day, and year of implantation were
      examined as fixed effects. RESULTS: Of the 52 patients, 62% of the patients were
      Federation Internationale de Gynecologie et d'Obstetrique Stage 2B, 88% were
      treated with concurrent chemotherapy, and 23% were treated at an outside facility
      and referred for the procedure. The mean times (minutes) for each step were as
      follows: preoperative evaluation, 93; insertion, 23; imaging, 45; treatment
      planning, 137; treatment, removal, and recovery, 115; total clinic time, 401. For
      the insertion time, the greater implant number per patient was significantly
      associated with a decreased total insertion time, with and without adjusting for
      other covariates, p = 0.002 and p = 0.0005, respectively. Treatment planning time
      was expedited with increasing number of implant per patient and comparing
      treatment times in 2012 with those in 2010, p = 0.01 and p < 0.0001,
      respectively. CONCLUSIONS: Gynecologic brachytherapy requires a skillfully
      coordinated and efficient team approach. Identifying critical components and the
      time required for each step in the process is needed to improve the safety and
      efficiency of brachytherapy. Continuous efforts should be made to enhance the
      optimal treatment delivery in high-dose-rate gynecologic brachytherapy.

PMID- 24559794
TI  - Phase II trial of image-based high-dose-rate interstitial brachytherapy for
      previously irradiated gynecologic cancer.
AB  - PURPOSE: To report the disease-free Grade >=3 complication-free survival of a
      Phase II protocol of reirradiation with high-dose-rate (HDR) interstitial
      brachytherapy (ITB) in previously irradiated gynecologic cancer. METHODS AND
      MATERIALS: Fifteen patients with previously irradiated cervical (n = 6),
      endometrial (n = 6), and vulvovaginal tumors (n = 3) were treated with HDR-ITB
      alone to a median dose of 38 Gy in 8 b.i.d. fractions over 4 consecutive days.
      Prior treatments included surgery (n = 12; 80%), external irradiation (n = 15;
      100%), and brachytherapy (n = 9; 60%). Average clinical target volume Size was
      60.9 cc (range, 14.8-165.3 cc), and median time to reirradiation was 3.9 years
      (range, 0.4-22.7 years). RESULTS: With a median followup of 2.8 years (range, 1.2
      9.2 years), 3 patients (20.0%) developed Grade >=3 toxicity consisting of Grade 3
      intestinal obstruction (n = 1), Grade 4 rectovesical fistula (n = 1), and Grade 5
      intestinal obstruction (n = 1). Six patients remain alive and without evidence of
      disease at last followup. Two patients are alive with disease progression, and 7
      patients have died, 4 of them from disease progression and 3 from other causes.
      The 2-year disease-free Grade >=3 complication-free survival was 40%.
      CONCLUSIONS: HDR-ITB alone is a reasonable salvage treatment option in a
      significant number of patients with previously irradiated gynecologic tumors.

PMID- 24559795
TI  - Sector analysis of dosimetry of prostate cancer patients treated with low-dose
      rate brachytherapy.
AB  - PURPOSE: Brachytherapy is an effective single treatment modality for low- and
      intermediate-risk prostate cancer. Here, we compare the radiation doses in
      different prostate sectors between the preimplant planning images and the
      postimplant dosimetry. METHODS AND MATERIALS: Two hundred fifteen consecutive
      patients treated for prostate cancer by (125)I seed brachytherapy were assessed.
      Pretreatment plans using transrectal ultrasound images of the prostate were
      compared with the dose calculated on posttreatment MRI and CT scans obtained 1
      month after seed implantation. Twelve sectors were generated by dividing the
      prostate base, midgland, and apex into four quadrants each. Pretreatment and
      posttreatment dosimetry were compared between the 12 different sectors of the
      prostate. RESULTS: Average V100 (percentage of prostate volume that receives 100%
      of the prescribed dose) in the preimplant planning images of the prostate was
      99.9 +/- 0.25% compared with postimplant V100 of 94.8 +/- 3.77% (p < 0.0001).
      Prostate V100 in the postimplant dosimetry was >91% in all sectors, except the
      anterior base sector, in which it was 64.87 +/- 20.96%. Average 1-month D90 (the
      dose to 90% of the prostate volume) was 114.5 +/- 10.55%. D90 at 1 month compared
      with preimplant planning was lower in the prostate base and higher in the
      prostate apex (p < 0.001). CONCLUSIONS: Our results show that in (125)I seed
      brachytherapy, prostate base receives a lower dose and apex receives a higher
      dose compared with preimplant planned dose coverage.

PMID- 24559796
TI  - [Non-invasive fetal RHD genotyping: Validation of the method with 200 patients].
AB  - BACKGROUND: Non-invasive fetal RHD genotyping is an important tool to assess the
      risk of fetuse's hemolytic disease of anti-D allo-immunized pregnant woman by non
      invasive method. A method of genotyping has been developed in the laboratory of
      Lyon-GHE according to Minon's team (J Gynecol Obstet Biol Reprod 2005): exon 4,
      5, and 10 are amplified by real time PCR. At first, genotyping results of 200
      pregnant women have been compared with RH1 phenotype at birth. The most important
      parameters of validation have been tested: the sensibility and the specificity;
      the negative predictive value; the correlation study permitted to define criteria
      of biological interpretation. The validation of this method permitted to
      determine critical points and the limits of the method due to the minor amount of
      fetal DNA in the maternal plasma and existence of many variant forms of the RHD
      gene. CONCLUSION: We worked too in the perspective to the accreditation for our
      genetic laboratory.

PMID- 24559798
TI  - GPR and bulk ground resistivity surveys in graveyards: locating unmarked burials
      in contrasting soil types.
AB  - With graveyards and cemeteries globally being increasingly designated as full,
      there is a growing need to identify unmarked burial positions to find burial
      space or exhume and re-inter if necessary. In some countries, for example the
      U.S. and U.K., burial sites are not usually re-used; however, most graveyard and
      cemetery records do not have maps of positions. One non-invasive detection method
      is near-surface geophysics, but there has been a lack of research to-date on
      optimal methods and/or equipment configuration. This paper presents three case
      studies in contrasting burial environments, soil types, burial styles and ages in
      the U.K. Geophysical survey results reveal unmarked burials could be effectively
      identified from these case studies that were not uniform or predicted using 225
      MHz frequency antennae GPR 2D 0.5 m spaced profiles. Bulk ground electrical
      surveys, rarely used for unmarked burials, revealed 1 m probe spacings were
      optimal compared to 0.5 m, with datasets needing 3D detrending to reveal burial
      positions. Results were variable depending upon soil type; in very coarse soils
      GPR was optimal; whereas resistivity was optimal in clay-rich soils and both were
      optimal in sandy and black earth soils. Archaeological excavations revealed
      unmarked burials, extra/missing individuals from parish records and a variety of
      burial styles from isolated, brick-lined, to vertically stacked individuals.
      Study results, evidence unmarked burial targets were significantly different from
      clandestine burials of murder victims which are used as analogues. 

PMID- 24559799
TI  - Using an SBAR - keeping it real! Demonstrating how improving safe care delivery
      has been incorporated into a top-up degree programme.
AB  - Using a standard communication tool can enhance and provide focus, to ensure that
      communication is accurately recorded and understood (Marquis and Huston, 2009).
      The Situation, Background, Assessment and Recommendation (SBAR) approach is
      common place in healthcare situations today (Institute for Health Improvement,
      2011), thus justifying the use of this contemporary way of communicating to
      structure this article. Patient safety, clinical effectiveness and person centred
      approaches to care, are top priorities in healthcare today. As nursing is in
      transition to an all degree profession, these dimensions of care should be
      integral to any "top-up" qualification. This paper discusses how this current
      clinical agenda was embedded into a top-up degree along with improvement
      methodology, in order to prepare newly graduated nurses for the world of modern
      healthcare. The module was developed and delivered in collaboration with clinical
      practice to maintain credibility and realism for the students. Based on Salmon's
      model of e-learning (Salmon, 2004), the completely online delivery meant that the
      students learning occurred whilst clinically based, allowing for theory and
      practice to interweave in a meaningful way, resulting in actual quality
      improvement. 

PMID- 24559797
TI  - Equine mesenchymal stem cells from bone marrow, adipose tissue and umbilical
      cord: immunophenotypic characterization and differentiation potential.
AB  - INTRODUCTION: Studies with mesenchymal stem cells (MSCs) are increasing due to
      their immunomodulatory, anti-inflammatory and tissue regenerative properties.
      However, there is still no agreement about the best source of equine MSCs for a
      bank for allogeneic therapy. The aim of this study was to evaluate the cell
      culture and immunophenotypic characteristics and differentiation potential of
      equine MSCs from bone marrow (BM-MSCs), adipose tissue (AT-MSCs) and umbilical
      cord (UC-MSCs) under identical in vitro conditions, to compare these sources for
      research or an allogeneic therapy cell bank. METHODS: The BM-MSCs, AT-MSCs and UC
      MSCs were cultured and evaluated in vitro for their osteogenic, adipogenic and
      chondrogenic differentiation potential. Additionally, MSCs were assessed for
      CD105, CD44, CD34, CD90 and MHC-II markers by flow cytometry, and MHC-II was also
      assessed by immunocytochemistry. To interpret the flow cytometry results,
      statistical analysis was performed using ANOVA. RESULTS: The harvesting and
      culturing procedures of BM-MSCs, AT-MSCs and UC-MSCs were feasible, with an
      average cell growth until the third passage of 25 days for BM-MSCs, 15 days for
      AT-MSCs and 26 days for UC-MSCs. MSCs from all sources were able to differentiate
      into osteogenic (after 10 days for BM-MSCs and AT-MSCs and 15 days for UC-MSCs),
      adipogenic (after 8 days for BM-MSCs and AT-MSCs and 15 days for UC-MSCs) and
      chondrogenic (after 21 days for BM-MSCs, AT-MSCs and UC-MSCs) lineages. MSCs
      showed high expression of CD105, CD44 and CD90 and low or negative expression of
      CD34 and MHC-II. The MHC-II was not detected by immunocytochemistry techniques in
      any of the MSCs studied. CONCLUSIONS: The BM, AT and UC are feasible sources for
      harvesting equine MSCs, and their immunophenotypic and multipotency
      characteristics attained minimal criteria for defining MSCs. Due to the low
      expression of MHC-II by MSCs, all of the sources could be used in clinical trials
      involving allogeneic therapy in horses. However, the BM-MSCs and AT-MSCs showed
      fastest ''in vitro'' differentiation and AT-MSCs showed highest cell growth until
      third passage. These findings suggest that BM and AT may be preferable for cell
      banking purposes.

PMID- 24559800
TI  - Disaster-related environmental health hazards: former lead smelting plants in the
      United States.
AB  - OBJECTIVE: Natural disasters exacerbate risks of hazardous environmental
      exposures and adverse health consequences. The present study determined the
      proportion of previously identified lead industrial sites in urban locations that
      are at high risk for dispersal of toxic chemicals by natural disasters. METHODS:
      Geographic analysis from publicly available data identified former lead smelting
      plants that coincide with populated urban areas and with high-risk locations for
      natural disasters. RESULTS: From a total of 229 urban smelting sites, 66 (29%)
      were in relatively high-risk areas for natural disasters: flood (39), earthquake
      (29), tornado (3), and hurricane (2). States with urban sites at relatively high
      risk for natural disaster included California (15); Pennsylvania (14); New York
      (7); Missouri (6); Illinois (5); New Jersey (4); Kentucky (3); Florida, Oregon,
      and Ohio (2 each); and Indiana, Massachusetts, Rhode Island, Texas, Utah, and
      Washington (1 each). Incomplete historical records showed at least 10 smelting
      site locations were affected by natural disaster. CONCLUSIONS: Forgotten
      environmental hazards may remain hazardous in any community. Uncertainty about
      risks in disasters causes disruptive public anxiety that increases difficulties
      in community responses and recovery. Our professional and public responsibility
      is to seek a better understanding of the risks of latent environmental hazards.

PMID- 24559801
TI  - Decreased sympathetic tone after short-term treatment with enalapril in dogs with
      mild chronic mitral valve disease.
AB  - Heart rate variability (HRV) and echocardiography were performed in 14 dogs with
      mitral regurgitation (MR) before and after 14 days of 0.5mg/kg/day of enalapril
      treatment. All dogs were in heart failure stages B1 and B2. After enalapril
      treatment, left ventricular end diastolic diameter (LVEDd), left ventricular end
      diastolic diameter normalized for body weight (LVEDdN) and percent mitral
      regurgitant jet decreased (P<0.05). The diastolic blood pressure decreased
      (P<0.05). Increased time domain parameters of HRV were found. For frequency
      domain analysis, the total frequency (TF) increased significantly (P<0.05). The
      normalized low frequency (LF norm) decreased while normalized high frequency (HF
      norm) increased causing significant reduction in LF/HF (P<0.05). Before enalapril
      treatment, LF was correlated with end diastolic volume (EDV) (P<0.01) and LVEDd
      (P<0.05). In conclusion, MR dogs receiving enalapril treatment for 14 days had
      increased cardiac parasympathetic tone while sympathetic tone was suppressed. The
      decreased sympathetic activity corresponded to the reduction in cardiac preload
      and afterload.

PMID- 24559802
TI  - Organizing pneumonia: what is it? A conceptual approach and pictorial review.
AB  - Organizing pneumonia (formerly named bronchiolitis obliterans with organizing
      pneumonia or BOOP) is a clinical, radiological and histological entity that is
      classified as an Interstitial Lung Disease. The understanding of this family of
      diseases has seen great progress over the past twenty years. CT presentation of
      organizing pneumonia is polymorphous but a few patterns have been recently
      recognized as being more specific to this diagnosis. The aim of this work is to
      summarize new understandings of the clinical and histological presentation of the
      disease and to review the most relevant CT features. 

PMID- 24559804
TI  - Can whole-body MRI replace (18)F-fluorodeoxyglucose PET/CT?

PMID- 24559803
TI  - Ionising radiation-free whole-body MRI versus (18)F-fluorodeoxyglucose PET/CT
      scans for children and young adults with cancer: a prospective, non-randomised,
      single-centre study.
AB  - BACKGROUND: Imaging tests are essential for staging of children with cancer.
      However, CT and radiotracer-based imaging procedures are associated with
      substantial exposure to ionising radiation and risk of secondary cancer
      development later in life. Our aim was to create a highly effective, clinically
      feasible, ionising radiation-free staging method based on whole-body diffusion
      weighted MRI and the iron supplement ferumoxytol, used off-label as a contrast
      agent. METHODS: We compared whole-body diffusion-weighted MRI with standard
      clinical (18)F-fluorodeoxyglucose ((18)F-FDG) PET/CT scans in children and young
      adults with malignant lymphomas and sarcomas. Whole-body diffusion-weighted
      magnetic resonance images were generated by coregistration of colour-encoded
      ferumoxytol-enhanced whole-body diffusion-weighted MRI scans for tumour detection
      with ferumoxytol-enhanced T1-weighted MRI scans for anatomical orientation,
      similar to the concept of integrated (18)F-FDG PET/CT scans. Tumour staging
      results were compared using Cohen's kappa statistics. Histopathology and follow
      up imaging served as the standard of reference. Data was assessed in the per
      protocol population. This study is registered with ClinicalTrials.gov, number
      NCT01542879. FINDINGS: 22 of 23 recruited patients were analysed because one
      patient discontinued before completion of the whole-body scan. Mean exposure to
      ionising radiation was 12.5 mSv (SD 4.1) for (18)F-FDG PET/CT compared with zero
      for whole-body diffusion-weighted MRI. (18)F-FDG PET/CT detected 163 of 174
      malignant lesions at 1325 anatomical regions and whole-body diffusion-weighted
      MRI detected 158. Comparing (18)F-FDG PET/CT to whole-body diffusion-weighted
      MRI, sensitivities were 93.7% (95% CI 89.0-96.8) versus 90.8% (85.5-94.7);
      specificities 97.7% (95% CI 96.7-98.5) versus 99.5% (98.9-99.8); and diagnostic
      accuracies 97.2% (93.6-99.4) versus 98.3% (97.4-99.2). Tumour staging results
      showed very good agreement between both imaging modalities with a kappa of 0.93
      (0.81-1.00). No adverse events after administration of ferumoxytol were recorded.
      INTERPRETATION: Ferumoxytol-enhanced whole-body diffusion-weighted MRI could be
      an alternative to (18)F-FDG PET/CT for staging of children and young adults with
      cancer that is free of ionising radiation. This new imaging test might help to
      prevent long-term side-effects from radiographic staging procedures. FUNDING:
      Thrasher Research Fund and Clinical Health Research Institute at Stanford
      University.

PMID- 24559805
TI  - Reporting guidelines: in the future for JPHC?

PMID- 24559806
TI  - Pediatric falls from windows: a health policy model for prevention.

PMID- 24559807
TI  - Child neglect: assessment and intervention.
AB  - Neglect is often a neglected form of child maltreatment even though it is the
      most common and deadliest form of child maltreatment. Pediatric nurse
      practitioners (PNPs) will most likely encounter neglected children in their
      practice. It is crucial that PNPs recognize child neglect in a timely manner and
      intervene appropriately. This continuing education article will help PNPs
      understand and respond to child neglect. Neglect will be defined and risk factors
      will be discussed. Children who are neglected can experience serious and lifelong
      consequences. The medical assessment and plan of care for children with concerns
      of suspected neglect will be discussed. 

PMID- 24559808
TI  - Cyberbullying resources for youth and their families.

PMID- 24559809
TI  - Hypnotherapy is more effective than nicotine replacement therapy for smoking
      cessation: results of a randomized controlled trial.
AB  - BACKGROUND: The efficacy of pharmacotherapy for smoking cessation is well
      documented. However, due to relapse rates and side effects, hypnotherapy is
      gaining attention as an alternative treatment option. The aim of this one-center
      randomized study was to compare the efficacy of hypnotherapy alone, as well as
      hypnotherapy with nicotine replacement therapy (NRT), to conventional NRT in
      patients hospitalized with a cardiac or pulmonary illness. METHODS: We evaluated
      self-reported and biochemically verified 7-day prevalence smoking abstinence
      rates at 12 and 26 weeks post-hospitalization. Patients (n=164) were randomized
      into one of three counseling-based treatment groups: NRT for 30 days (NRT; n=41),
      a 90-min hypnotherapy session (H; n=39), and NRT with hypnotherapy (HNRT; n=37).
      Treatment groups were compared to a "self-quit" group of 35 patients who refused
      intervention. RESULTS: Hypnotherapy patients were more likely than NRT patients
      to be nonsmokers at 12 weeks (43.9% vs. 28.2%; p=0.14) and 26 weeks after
      hospitalization (36.6% vs. 18.0%; p=0.06). Smoking abstinence rates in the HNRT
      group were similar to the H group. There was no difference in smoking abstinence
      rates at 26 weeks between "self quit" and participants in any of the treatment
      groups. In multivariable regression analysis adjusting for diagnosis and
      demographic characteristics, H and HNRT were over three times more likely than
      NRT participants to abstain at 26-weeks post-discharge (RR=3.6; p=0.03 and
      RR=3.2; p=0.04, respectively). CONCLUSION: Hypnotherapy is more effective than
      NRT in improving smoking abstinence in patients hospitalized for a smoking
      related illness, and could be an asset to post-discharge smoking cessation
      programs.

PMID- 24559810
TI  - The effect of ginger powder supplementation on insulin resistance and glycemic
      indices in patients with type 2 diabetes: a randomized, double-blind, placebo
      controlled trial.
AB  - OBJECTIVE: To identify the effect of some herbal products on insulin resistance.
      Regarding the scientific evidences existing about ginger, this research was
      therefore carried out to identify the effect of ginger supplementation on insulin
      resistance and glycemic indices in diabetes mellitus. METHODS: This is a
      randomized, double-blind, placebo-controlled trial in which 88 participants
      affected by diabetes were randomly assigned into ginger (GG) and placebo (PG)
      groups. The GG received 3 one-gram capsules containing ginger powder whereas the
      PG received 3 one-gram microcrystalline-containing capsules daily for 8 weeks.
      HbA1c, fructosamine, fasting blood sugar (FBS), fasting insulin, homeostasis
      model assessment insulin resistance index (HOMA-IR), beta-cell function (beta%),
      insulin sensitivity (S%) and the quantitative insulin sensitivity check index
      (QUICKI) were assessed before and after the intervention. RESULTS: FBS mean
      showed a decrease of 10.5% (p=0.003) in the GG whereas the mean had an increase
      of 21% in the PG (p=0.01). Variation in HbA1c mean was in line with that of FBS.
      Statistical difference was found in the two groups before and after the
      intervention in terms of median of fasting insulin level, S% and HOMA-IR
      (P<0.005). Moreover QUICKI mean increased significantly in the two groups, the
      mean difference, however, was significantly higher in the GG. CONCLUSIONS: The
      study demonstrated that daily consumption of 3 one-gram capsules of ginger powder
      for 8 weeks is useful for patients with type 2 diabetes due to FBS and HbA1c
      reduction and improvement of insulin resistance indices such as QUICKI index.

PMID- 24559811
TI  - Is ginger effective for the treatment of irritable bowel syndrome? A double blind
      randomized controlled pilot trial.
AB  - OBJECTIVES: Ginger is one of the most commonly used herbal medicines for
      irritable bowel syndrome (IBS) but no data exists about its effectiveness.
      DESIGN: Double blind randomized controlled trial. SETTING: University of North
      Carolina, Chapel Hill, North Carolina, USA. INTERVENTION: Forty-five IBS patients
      were randomly assigned to three groups: placebo, 1g of ginger, and 2g of ginger
      daily for 28 days. MAIN OUTCOME MEASURES: The IBS severity scale (IBS-SS) was
      administered, as well as adequate relief of symptoms scale. A responder was
      defined as having at least 25% reduction in IBS-SS post-treatment. RESULTS: There
      were 57.1% responders to placebo, 46.7% to 1g and 33.3% to 2g of ginger. Adequate
      relief was reported by 53.3% on placebo and 53.3% in both ginger groups combined.
      Side effects were mild and reported by 35.7% in the placebo and 16.7% in the
      ginger groups. CONCLUSIONS: This double blind randomized controlled pilot study
      suggests ginger is well tolerated but did not perform better than placebo. Larger
      trials are needed before any definitive conclusions can be drawn.

PMID- 24559812
TI  - The effects of auricular electroacupuncture on obesity in female patients--a
      prospective randomized placebo-controlled pilot study.
AB  - BACKGROUND: Obesity is a chronic condition related to serious morbidity and
      mortality of increasing incidence and prevalence. Several studies show a
      significantly higher weight loss with acupuncture treatment. This is the first
      prospective, randomized, double-blinded study, testing the effects of auricular
      electroacupuncture on weight loss in obese female patients. METHODS: 56 female
      obese patients (age>18, Body Mass Index, BMI>25) were randomized to receive
      either auricular acupuncture with electrical stimulation with a P-Stim(r) device
      (verum group, n=28) or placebo treatment with a P-Stim(r) dummy (n=28) for four
      days. Three auricular acupuncture points were chosen (hunger 18, stomach 87 and
      colon 91). The treatment was performed once a week for a period of six weeks. A
      follow-up visit was performed after 4 weeks. At each visit body weight, BMI (Body
      Mass Index) and body fat were measured. RESULTS: Relative reduction of body
      weight was significantly greater in the verum group (-3.73%; CI=-4.70 to -2.76)
      than in the placebo group (-0.70%; CI=-1.57 to +0.16; p<0.001) In addition we
      also observed a significant reduction of BMI (p<0.001) in the verum group (
      3.62%; CI=-4.39 to -2.84) compared to placebo (-0.82%; CI=-1.55 to -0.10;
      p<0.001). No patient reported side effects related to acupuncture. CONCLUSION: In
      conclusion electrical auricular acupuncture could be a safe, additive, non
      pharmacological treatment in obese patients.

PMID- 24559813
TI  - The effectiveness of Swedish massage with aromatic ginger oil in treating chronic
      low back pain in older adults: a randomized controlled trial.
AB  - OBJECTIVES: To investigate the effects of Swedish massage with aromatic ginger
      oil (SMGO) on chronic low back pain and disability in older adults compared with
      traditional Thai massage (TTM). DESIGN: Randomized controlled trial. SETTING:
      Massage clinic in Ratchaburi province, Thailand. PARTICIPANTS: 164 patients were
      screened; 140 were eligible, and randomized to either SMGO (n=70) or TTM (n=70).
      INTERVENTION: Trained staff provided participants with a 30-min SMGO or TTM twice
      a week for five weeks. MEASUREMENT: The Visual Analogue Scale (VAS) assessed
      immediate effect (after each massage) and the short form McGill Pain
      Questionnaire (MPQ) assessed effectiveness of massage in short-term (six weeks)
      and long-term (15 weeks). Disability improvement was measured by the Owestry
      Disability Questionnaire (ODQ) at baseline, short- and long-term. RESULTS: Both
      SMGO and TTM led to significant improvements in pain intensity (p<0.05) and
      disability (p<0.05) across the period of assessments, indicating immediate, short
      and long-term effectiveness. SMGO was more effective than TTM in reducing pain
      (p=0.04) and improving disability at short- and long-term assessments (p=0.04).
      CONCLUSIONS: These findings suggest that the integration of either SMGO or TTM
      therapy as additional options to provide holistic care to older people with
      chronic low back pain could be considered by health professionals. Further
      research into the use of ginger as an adjunct to massage therapy, particularly
      TTM, is recommended.

PMID- 24559814
TI  - Efficacy and safety of topical Trikatu preparation in, relieving mosquito bite
      reactions: a randomized controlled trial.
AB  - INTRODUCTION: Trikatu is composed of dried fruits of Piper nigrum L and Piper
      retrofractum Vahl, and dried rhizomes of Zingiber officinale R. Although this
      preparation has been used to relieve pruritis, pain, and inflammation for a long
      time, there is no clinical evidence to confirm its efficacy and safety.
      Therefore, we performed a double-blind, within person-randomized controlled study
      of 30 healthy volunteers to determine efficacy and safety of topical Trikatu on
      mosquito bite reactions. METHODS: All subjects were bitten by Aedes aegypti
      laboratory mosquitoes on their forearms and they were randomly assigned arms to
      apply either Trikatu or reference product on the mosquito bite papule. The main
      outcome was the difference of papule size reduction at 30 min, measured by a
      caliper, between the Trikatu and reference arms. Pruritis, redness, pain, and
      patient satisfaction were assessed at 15, 30, 60, 180, and 360 min as secondary
      outcomes. RESULTS: There were no significant differences between treatment and
      reference arms on any outcome at any time of measurement. CONCLUSION: Trikatu did
      not show additional effects for relieving mosquito bite reaction as compared with
      the reference product containing camphor, menthol, and eucalyptus. For further
      study, it is very important to consider a proper selection of subjects,
      comparator product, and concentration of extract when Trikatu preparation is
      investigated.

PMID- 24559815
TI  - The effect of coix seed on the nutritional status of peritoneal dialysis
      patients: a pilot study.
AB  - OBJECTIVE: To observe the effect of coix seed diet therapy on the nutritional
      status of peritoneal dialysis patients and to discuss the potential reasons.
      METHODS: 30 dialysis patients with regular return visit to peritoneal dialysis
      center of Guangdong Provincial Hospital of Traditional Chinese Medicine were
      recruited and divided into two groups according to their willingness. 13 patients
      in control group continued their usual dialysis prescriptions and medications,
      whereas 30g of coix seed per day was added to the usual therapies of 17 patients
      in coix seed group. Changes in nutritional status of dialysis patients in two
      groups were evaluated after a 12-week treatment. RESULTS: Two patients (one in
      each group) quitted the study because of pulmonary infection. After treatment,
      the nutritional parameters of serum albumin level (P=0.004), total protein level
      (P=0.008), and body mass index (P=0.023) were increased significantly in coix
      seed group. And the statistical differences of serum albumin level and body mass
      index were significantly compared to control group (P=0.008 and P=0.032,
      respectively). Moreover, the C-reactive protein level had a significant decrease
      (P=0.001) and the clinical symptoms of dialysis patients including tiredness,
      anorexia, xerostomia, and abdominal distension showed a significant improvement
      (P<0.05) in coix seed group. And urinary volume of dialysis patients in coix seed
      group also had a significant increase (P=0.027). However, there is no significant
      difference showed in control group. CONCLUSION: Coix seed diet therapy plays a
      role in improving the nutritional status of peritoneal dialysis patients by
      relieving digestive tract symptoms, increasing urinary volume, and meliorating
      micro-inflammatory state. But as a pilot study, the results still need to be
      validated by further large-scale researches.

PMID- 24559816
TI  - The effects of sedative music on sleep quality of older community-dwelling adults
      in Singapore.
AB  - OBJECTIVES: To examine the effects of music listening on sleep quality amongst
      older community-dwelling adults in Singapore. METHODS: In a randomized controlled
      study, a cohort of older adults (N=60) age 55 years or above were recruited in
      one community centre. Sleep quality, as measured by the Pittsburgh Sleep Quality
      Index (PSQI), was the primary outcome. Participants' demographic variables
      including age, gender, religion, education level, marital and financial status,
      any chronic illness, previous experiences of music intervention as well as
      depression levels were collected. Participants were asked to listen to soft,
      instrumental slow sedative music without lyrics, of approximately 60-80 beats per
      minute, and 40 min in duration, for 6 weeks. Generalized estimating equations
      were used to examine the effects of the intervention on the elders' sleep
      quality. RESULTS: Significant reductions in PSQI scores were found in the
      intervention group (n=28) from baseline (mean+/-SD, 10.2+/-2.5) to week 6 (5.9+/
      2.4, p<0.001), while there were no changes in the control group (n=32) from
      baseline (9.0+/-2.4) to week 6 (9.5+/-2.6). At week 6, the intervention group
      showed a better sleep quality than the control (chi(2)=61.84, p<0.001).
      CONCLUSIONS: Notwithstanding the placebo effect, this study supports music
      listening as an effective intervention for older adults to improve sleep quality.
      Not only does this process improve their sleeping quality at old age, it also
      individualizes and enhances the quality of care provided by the healthcare
      provider as the therapeutic relationship between provider and client is being
      established. Contemporary gerontology is progressively characterized by
      collaboration between several approaches with the intent to comprehend the mental
      aspects of the multifarious process of ageing. Music listening is one such avenue
      to enhance sleep quality amongst older adults and make an essential contribution
      to healthy ageing.

PMID- 24559817
TI  - Active music therapy improves cognition and behaviour in chronic vascular
      encephalopathy: a case report.
AB  - OBJECTIVES: This study describes the effects of active music therapy (AMT) on
      cognition and behaviour in chronic vascular encephalopathy. DESIGN: A single case
      study investigated different cognitive and psycho-behavioural changes after AMT.
      SETTING: An adult patient with memory, attention, and verbal fluency deficits
      associated with Vascular Cognitive Impairment-No Dementia (VCI-ND) was treated.
      INTERVENTION: A four-months AMT course was based on creative and interactive
      music playing. Sixteen sessions were conducted simultaneously to the
      pharmacological therapy. MAIN OUTCOMES MEASURES: Cognitive performances, mood,
      interpersonal interactions, and perceived abilities were assessed using
      standardized neuropsychological and psycho-behavioural measurements. RESULTS: At
      baseline, the patient reported a tendency to feel tense, nervous, and angry and
      difficulties in memory and visuospatial performances, frequently accompanied by
      attention drops. The social network was a habitual component of the patient's
      life, but not a source of sharing of personal experiences, safety or comfort.
      Neuropsychological tests showed deficits in object and figure naming, verbal
      fluency, short and long-term verbal memory, short-term spatial memory, selective
      attention, and visuomotor coordination. After AMT, the cognitive profile
      significantly improved in attention, visuomotor coordination, and verbal and
      spatial memory. Such positive changes were confirmed at the three-months follow
      up. An increase of the interpersonal interactions and consistent reduction of
      anxiety were also observed. CONCLUSIONS: In selected patients with VCI-ND, a well
      structured AMT intervention added to standard therapy may contribute in
      determining a stable improvement of cognitive and psycho-behavioural aspects.
      Controlled studies are needed to confirm these promising results.

PMID- 24559818
TI  - A case series on the use of lavendula oil capsules in patients suffering from
      major depressive disorder and symptoms of psychomotor agitation, insomnia and
      anxiety.
AB  - OBJECTIVE: Symptoms of agitation, anxiety and insomnia are frequent among
      patients with major depressive disorder (MDD) during the first weeks of
      psychiatric care. But a substantial number of patients declines taking
      pharmaceutical medication to avoid side effects. Therefore, an alternative herbal
      medication is needed. Clinical studies demonstrated that lavender oil capsules,
      termed Lasea(r), have an anxiolytic effect comparable to Lorazepam and
      significantly reduce insomnia and agitation in non-depressed patients. Therefore,
      the aim of this retrospective case series was to analyze the effectiveness of
      Lasea(r) for patients with MDD and symptoms of anxiety, insomnia and psychomotor
      agitation. DESIGN: Eight cases were analyzed retrospectively regarding the
      dosage, length of treatment, possible side effects and effectiveness of Lasea(r).
      SETTING: All cases were treated at the Department of Psychiatry at Charite
      Universitatsmedizin Berlin, Campus Benjamin Franklin in a naturalistic setting.
      MAIN OUTCOME MEASURE: Effectiveness was measured by a change in the Hamilton
      Rating Scale for Depression (HAMD-17) total score and subscores. RESULTS: In 6
      cases, the combination of Lasea(r) and an antidepressant resulted in a reduction
      of MDD. Lasea(r) also reduced agitation in 6 cases. Psychological anxiety was
      reduced in 5, somatic anxiety in 4 cases whereas sleep-onset and sleep
      maintenance insomnia improved in 3 cases each. CONCLUSIONS: The results
      demonstrate that Lasea(r) reduces some of the anxiety related symptoms and sleep
      disturbances in MDD patients. Furthermore Lasea(r) significantly reduces
      psychomotor agitation. Additionally, the results indicate a significant global
      improvement stemming from the combinational therapy of Lasea(r) and
      antidepressant medication.

PMID- 24559819
TI  - Eighteen cases of liver injury following ingestion of Polygonum multiflorum.
AB  - OBJECTIVES: Polygonum multiflorum is a popular Chinese herbal medication. In this
      case series, we report on 18 otherwise healthy non-viral hepatitis patients who
      developed liver dysfunction following consumption of P. multiflorum alone.
      METHODS: Concurrent and retrospective analysis was used in this study. The
      causality of P. multiflorum in liver injury was graded by the Council for
      International Organizations of Medical Sciences (CIOMS) toxicity scale. RESULTS:
      From 2005 to 2012, 18 cases of hepatotoxicity potentially involving P.
      multiflorum. The median age was 42 years old (range from 18 to 63). Median time
      of onset of symptoms was 27 days (1-120). Prevailing clinical symptoms were
      fatigue, loss of appetite and jaundice. Sixteen patients had elevated level of
      total bilirubin (>21 mol/L); liver enzymes elevated markedly in all patients
      (ALT>40 U/L, AST>40 U/L, GGT>50 U/L), except for alkaline phosphatase which
      elevated only in nine patients. Based on the liver enzyme pattern, the type of
      liver injuries were hepatocellular according to CIOMS. In terms of causality, 14
      of 18 patients were evaluated as being highly probable. All patients were
      responding well to P. multiflorum stoppage, and liver protective-supportive care.
      CONCLUSIONS: P. multiflorum products can be associated with hepatotoxicity in
      otherwise healthy non-viral hepatitis infected patients, regardless of herbal
      processing.

PMID- 24559820
TI  - The practice of acupuncture and moxibustion to promote cephalic version for women
      with a breech presentation: implications for clinical practice and research.
AB  - OBJECTIVES: To examine what experienced acupuncture practitioners and researchers
      considered key aspects of treatment to promote cephalic version for women with a
      breech presentation, and to establish a treatment protocol through consensus to
      guide the self administration of moxa by pregnant women. METHODS AND DESIGN: The
      Delphi method was used to seek the opinions of key informants. Sixteen English
      speaking international, Australian and New Zealand acupuncturists working in the
      area of pregnancy were invited to participate in the study. Participants were
      given a link to an online survey, and their views sought on treatment parameters
      guiding the treatment of breech presentation within a research setting. RESULTS:
      Two rounds of the Delphi process were undertaken, 12 participants completed round
      one, and 10 completed round two. Eighty percent of participants agreed that moxa
      should commence between 34 and 35 weeks gestation. Ninety percent agreed to self
      administration of moxa by the woman, and use of smokeless and odourless sticks.
      Seventy percent agreed moxa should be applied for a minimum of 10 days, and be
      applied once a day for 30min. Monitoring safety was identified as an important
      outcome. Ninety percent agreed study clinical outcomes should assess side effects
      including burns, and maternal and foetal outcomes. CONCLUSION: Findings from our
      study promote the clinical validity for a future research protocol, and highlight
      other areas for research to evaluate the role of acupuncture and moxibustion with
      normalising birth.

PMID- 24559821
TI  - Herbalists' perception of risks involving commonly sold medicinal plants in
      Italy.
AB  - OBJECTIVE: Although there are several studies which have investigated
      pharmacists' knowledge of the safety of medicinal plants (MPs), no studies have
      examined herbalists' perception of risks associated with MPs. METHODS: We
      conducted a survey of 159 herbalists (participation rate 85.9%) in the region of
      Tuscany (Italy). Data were collected by means of a semi-structured questionnaire
      using a face-to-face interview. Risk perception was rated on a 10 cm Visual
      Analogic Scale (VAS). Herbalists' scores were then compared with those reported
      by a group of 10 experts in herbal medicine. RESULTS: When the overall risk was
      examined, herbalists had a low perception of the risks (VAS median ranged between
      1.5 and 3.2) associated with the use of most MPs (Allium sativum, Aloe vera gel,
      Echinacea spp., Escholtzia californica, Harpagophytum procumbens, and propolis).
      They had an intermediate or high perception of risks associated with use of
      Cimicifuga racemosa, Citrus aurantium, and Panax ginseng (median ranged between
      3.5 and 5.0), and for anthraquinone laxatives (median 7.2). Although the overall
      risk perceived by experts was generally higher than that reported by herbalists,
      differences were statistically significant only for Allium sativum and Escholtzia
      californica. CONCLUSION: The study shows that herbalists in Tuscany are
      knowledgeable about the relative risks of MPs when compared with experts in
      herbal medicine.

PMID- 24559823
TI  - The use of complementary and alternative medicine by women transitioning through
      menopause in Germany: results of a survey of women aged 45-60 years.
AB  - OBJECTIVES: To describe prevalence rates of complementary and alternative
      medicine therapies (CAM) for the relief of menopausal complaints among German
      women. Furthermore, to investigate the perceived effectiveness of these
      therapies. DESIGN: A self-administered questionnaire was sent to 9785 randomly
      selected women in Germany aged between 45 and 60 years. RESULTS: A total of 1893
      (19.3%) questionnaires have been sent back. The mean age of all participants was
      52.6+/-4.3 years. 81% (n=1517) of the responding women stated that they had
      experienced menopausal complaints at least once. Symptoms ranged from vasomotor
      symptoms, including hot flushes and night sweats, in 71.2% of cases, to bladder
      problems in 42.7%. The average symptom score (MRS II total score, range 1-44)
      among the respondents was 12.76+/-9.6. More than half (56%; n=1049/1872) of the
      responding women had used some form of therapy to alleviate their symptoms at
      least once. The majority of women undertaking a therapy (64.8%; n=679/1049) had
      used only CAM interventions (either one or more type of CAM), 14.2% (n=149) had
      used hormone replacement therapy (HRT) only, while 21.1% (n=221/1049) had tried
      both CAM and HRT. Popular CAM interventions by the respondents were an alteration
      of lifestyle (28.7%), St. John's wort (18.3%) and homoeopathy (14.9%). An
      alteration in lifestyle was rated as the most effective CAM treatment with 84.9%
      (n=457). Other treatments like hormone yoga (79.2%; n=42), homoeopathy (73.7%;
      n=205) and TCM (59.1%; n=94) were also perceived to be effective. Phytoestrogens
      were rated as the most ineffective (45.5%; n=50). CONCLUSION: CAM interventions
      to alleviate menopausal complaints are popular among German women, with 48.2%
      (n=900/1872) of respondents reporting having used CAM either alone or in
      combination with HRT. However, the users rated the effects of CAM differently,
      with some reporting CAM to be highly effective, while others indicate lower
      effectiveness. Nevertheless, women with a significantly higher symptom scoring
      tend to use both CAM and a conventional therapy (HRT).

PMID- 24559822
TI  - Predictive factors of complementary and alternative medicine use for patients
      with inflammatory bowel disease in Korea.
AB  - OBJECTIVES: The aim of this study was to assess characteristics and predictive
      factors of complementary and alternative medicine (CAM) use for patients with
      inflammatory bowel disease (IBD) in Korea. DESIGN: Prospective, questionnaire
      based study for patients with IBD in Korea. SETTING: Six university hospitals and
      one primary IBD clinic. MAIN OUTCOME MEASURE: Overall characteristics and
      predictors of CAM use were compared between CAM users and non-users. RESULTS:
      During the study period, 366 patients with IBD (ulcerative colitis=228, Crohn's
      disease=138) completed the full questionnaire; 29.5% (n=108) reported CAM use and
      70.5% (n=258) reported no CAM use after diagnosis of IBD. In total, 64.0% were
      male, the mean patient age was 42.3+/-15.5 years, and the mean duration of IBD
      was 5.5+/-5.8 years. Using logistic regression analysis, university education
      (p=0.040), higher income levels (p=0.009), and longer duration of IBD (p=0.003)
      were found to be independent predictors of CAM use. Among CAM users, 65% of CAM
      was attained within 2 years of IBD diagnosis and only 28.7% discussed CAM use
      with their physician. Furthermore, 13.9% of CAM users discontinued conventional
      IBD therapy while using CAM. CONCLUSIONS: The overall use of CAM in Korea was
      comparable with those in the West. Physicians should be aware of the high
      prevalence of CAM use by patients with IBD, especially among those with higher
      education levels, higher income levels, and longer IBD duration. Furthermore,
      physicians should ask about CAM use, and help their IBD patients make a more
      informed choice about CAM use.

PMID- 24559824
TI  - Comparison of the knowledge, attitudes and practice with antibiotic use between
      traditional Chinese medicine and western medicine usual attenders in Hong Kong.
AB  - BACKGROUND: Patients who usually attend Traditional Chinese Medicine (TCM) need
      to go to western medicine (WM) doctors for antibiotics in Hong Kong. They might
      have different knowledge, attitude and practice (KAP) with antibiotics from the
      WM-attenders. OBJECTIVE: This study compares TCM attenders with the WM-attenders
      in Hong Kong about their KAP with antibiotics. The comparison could help future
      campaigns/education on appropriate antibiotic use. DESIGN AND SETTING: A
      questionnaire on KAP with antibiotics was designed after eight focus groups of
      purposively selected participants. A territory-wide telephone survey then
      interviewed randomly selected residents who were aged 18 years or above and spoke
      the local dialect. RESULT: Of 2471 respondents, 270 and 2092 usually attended TCM
      and WM, respectively. Majority of both the TCM- and WM-attenders preferred
      doctors who were judicious in prescribing antibiotics and seldom asked for them.
      The TCM-attenders were significantly more likely to be female and with lower
      household income. They were also more likely to agree that antibiotics were not
      useful for upper respiratory tract infections and that antibiotic resistance was
      a serious local problem. They were less likely to accept or be treated with
      antibiotics. The TCM-attenders were also more concerned about the side-effects of
      antibiotics. However, they were also less likely than the WM-attenders to always
      finish a full course of antibiotic. CONCLUSION: Apart from non-compliance, the
      TCM-attenders' KAP with antibiotics favour the appropriate use of antibiotics.

PMID- 24559825
TI  - Complementary and alternative medicine (CAM) use and quality of life in people
      with type 2 diabetes and/or cardiovascular disease.
AB  - OBJECTIVES: To quantify the association between complementary and alternative
      medicine (CAM) use and quality of life in a population with type 2 diabetes
      and/or cardiovascular disease, accounting for demographics, socioeconomic status,
      health and lifestyle factors. DESIGN AND SETTING: Data are from a purpose
      designed survey of 2915 individuals aged 18 years and over, all with type 2
      diabetes and/or cardiovascular disease (CVD), collected in 2010. Key variables
      are compared for comparability with nationally representative data. It was
      hypothesised that CAM use would be associated with higher quality of life, as
      measured by the Assessment of Quality of Life-4 dimension (AQoL-4D) instrument.
      Three key variables are used for CAM use in the previous twelve months. In the
      robustness analysis, CAM use is further disaggregated into the types of
      practitioner or product used, the frequency of use, the reason for use and
      expenditure on CAM. RESULTS: CAM use is not associated with higher QoL for this
      sub-population, and in fact intensive use of CAM practitioners is associated with
      significantly lower QoL. CONCLUSIONS: It is important not to assume that patients
      have sufficient information with which to make optimal choices regarding CAM use
      in the absence of accessible and relevant evidence-based guidance.

PMID- 24559826
TI  - Investigation on Chinese herbal medicine for primary dysmenorrhea: implication
      from a nationwide prescription database in Taiwan.
AB  - OBJECTIVE: Primary dysmenorrhea is a common gynecological condition, for which
      Chinese herbal medicine (CHM) has been widely used in addition to western
      medicine. The aim of this study is to explore CHM commonly used to treat
      dysmenorrhea in young Chinese women. DESIGN: Observational retrospective study.
      SETTING: The National Health Insurance Research Database in Taiwan. POPULATION:
      Women aged from 13 to 25 years with single diagnosis of primary dysmenorrhea.
      METHODS: CHM prescriptions made for primary dysmenorrhea women during 1998-2008
      were extracted to build up CHM prescription database. Association rule mining was
      used to explore the prevalent CHM combination patterns in treating primary
      dysmenorrhea. MAIN OUTCOME MEASURES: Prevalence and mechanisms of CHM
      combinations. RESULTS: Totally 57,315 prescriptions were analyzed and, on
      average, 5.3 CHM was used in one prescription. Dang-Gui-Shao-Yao-San (DGSYS) was
      the most commonly used herbal formula (27.2%), followed by Jia-Wei-Xiao-Yao-San
      (JWXYS) (20.7%) and Wen-Jing-Tang (WJT) (20.5%). Corydalis yanhusuo and Cyperus
      rotundus were the most commonly used single herb, found in 33.1% and 29.2% of all
      prescriptions. Additionally, C. yanhusuo with C. rotundus is the most commonly
      used two CHM in combination, accounting for 14.24% of all prescriptions, followed
      by DGSYS with C. yanhusuo (10.47%). Multi-target effects on primary dysmenorrhea,
      such as analgesia, mood modifying and hormone adjustment, were found among
      commonly prescribed CHM in this study. CONCLUSIONS: This study discovered the
      potential importance of C. yanhusuo, C. rotundus and DGSYS in treating primary
      dysmenorrhea. Further clinical trials or bench studies are warranted based on the
      results.

PMID- 24559827
TI  - Knowledge, attitude and practice toward complementary and traditional medicine
      among Kashan health care staff, 2012.
AB  - OBJECTIVES: Studies show that medical staff in different countries have different
      attitudes toward traditional and complementary medicine. Therefore, the current
      study aimed to evaluate the knowledge, attitude and practice of complementary and
      traditional medicine by medical staff of Kashan, Iran. DESIGN: A cross-sectional
      study was performed. SETTING: A total of 378 questionnaires were distributed
      among health care team members in Kashan University of Medical Sciences in 2012.
      The questionnaire was consisted of 5 questions regarding demographic
      characteristics and 12 questions on knowledge, attitude and practice of
      traditional and complementary medicine. Data were analyzed using descriptive
      statistics. RESULTS: In total, 309 questionnaires were returned and 302
      questionnaires were analyzed. Among the participants, 60.9% were female. The mean
      age of subjects was 29.70+/-9.28 years. Totally, 88.4% of the participants had no
      previous education on complementary and traditional medicine, and 77.8% showed
      interest to learn in this area. Also, 57.6% of participants had the experience of
      personal use of complementary and traditional therapies. The commonly used
      methods were: herbal therapy, cupping and traditional bathing. Participants used
      traditional medicine mostly for digestive diseases, colds, migraine and
      headaches, skin disorders, losing weight, and diabetes. Moreover, 56% of
      participants had recommended complementary and traditional therapies to the
      others. CONCLUSIONS: Most of the participants had low level knowledge on
      complementary and traditional medicine, but expressed their interest to learn in
      this field. Therefore, training health care team members and especially nurses
      and doctors on the applications, benefits and side effects of complementary and
      traditional medicine is recommended.

PMID- 24559828
TI  - Self-prescribed complementary and alternative medicine use for back pain amongst
      a range of care options: results from a nationally representative sample of 1310
      women aged 60-65 years.
AB  - OBJECTIVE: To examine the prevalence and characteristics of women who self
      prescribe complementary and alternative medicine (CAM) for back pain. METHODS: A
      cross-sectional survey of a nationally-representative sample of women aged 60-65
      years from the Australian Longitudinal Study on Women's Health (ALSWH). RESULTS:
      A significant number of women (75.2%, n=985) self-prescribed one or more CAM for
      back pain in the previous twelve months. Use of self-prescribed CAM for back pain
      was not associated with socio-economic status. The most common self-prescribed
      CAM used by women was supplements (n=776, 59.2%), vitamins/minerals (n=592,
      45.2%), yoga/meditation (n=187, 14.3%), herbal medicines (n=172, 13.1%) and
      aromatherapy oils (n=112, 8.6%). Women who visited general practitioners (GPs)
      more than three times in the previous twelve months were 1.59 times (95% CI:
      1.14, 2.22) more likely to self-prescribe CAM for back pain than those women who
      did not visit GPs. Women who visited a pharmacist three or more times in the
      previous twelve months were 2.90 times (95% CI: 1.65, 5.09) more likely to self
      prescribe CAM for back pain than those women who did not visit a pharmacist.
      CONCLUSION: This study identifies substantial use of self-prescribed CAM by women
      for back pain regardless of their education, income or urban/rural residency. In
      order to ensure safe, effective practice it is important that all providing and
      managing health services for back pain sufferers remain mindful of patients'
      possible use of self-prescribed CAM.

PMID- 24559829
TI  - Characteristics and prescription patterns of traditional Chinese medicine in
      atopic dermatitis patients: ten-year experiences at a medical center in Taiwan.
AB  - OBJECTIVES: Complementary and alternative therapies in treating atopic dermatitis
      are not uncommon. However, substantial evidence and consensus on treating atopic
      dermatitis is lacking. The aim of this study is to investigate the
      characteristics and utilization of traditional Chinese medicine in patients with
      atopic dermatitis. DESIGN: We retrospectively collected patients with atopic
      dermatitis at the Chang Gung Memorial Hospital in Taiwan between 2002 and 2011.
      Patients' demographic data, duration and frequency of treatment, serum total
      immunoglobulin E levels, and traditional Chinese medicine treatment principles
      and prescription were analyzed. RESULTS: There were 4145 patients (8.8%) received
      traditional Chinese medicine therapy between 2002 and 2011. Among them, 2841
      (68.54%) chose TCM only and 1304 (31.46%) chose to combine TCM and WM therapies.
      Those who chose combination therapy were younger, and needed more times of visit
      and longer duration of treatment. The most frequent comorbid conditions accompany
      atopic dermatitis were allergic rhinitis (46.06%) and asthma (21.46%). Among the
      87,573 prescriptions written for Chinese medicine, the most frequently prescribed
      herbal formula and single herb were Xiao-Feng-San (Eliminate Wind Powder)
      (16.98%) and Bai-Xian-Pi (Cortex Dictamni) (12.68%), respectively. The most
      commonly used therapeutic principles of herbal formulas and single herbs were
      releasing exterior (20.23%) and clearing heat (41.93%), respectively. CONCLUSION:
      Our hospital-based study characterized the utilization patterns of traditional
      Chinese medicine in atopic dermatitis patients. This information could be used as
      references for clinical application and provide valuable information for future
      clinical trials.

PMID- 24559830
TI  - Mode of action of cupping--local metabolism and pain thresholds in neck pain
      patients and healthy subjects.
AB  - OBJECTIVES: Cupping worldwide has been part of traditional medicine systems and
      is in the western world used as CAM therapy mainly for treating pain syndromes.
      The mode of action is up to now unclear. In order to investigate its mechanism we
      measured in parallel metabolic changes in the tissue under the cupping glass and
      pressure pain thresholds. DESIGN AND INTERVENTIONS: In 12 volunteers (6 healthy
      subjects and 6 patients with chronic neck pain) a microdialysis system was
      implanted subcutaneously on both sides (left and right) above the trapezius
      muscle. After baseline measures cupping was performed at one randomly selected
      side (left or right), the other side served as control. Every 20 min during
      baseline measures and for 280 min after cupping, microdialysis probes for
      detection of lactate, pyruvate, glucose and glycerin were taken. In addition,
      pain thresholds were measured before and after cupping with algometry. RESULTS:
      Cupping resulted in a strong increase of lactate (beginning 160 min after cupping
      until the end of the measurements) and the lactate/pyruvate ratio, indicating an
      anaerobe metabolism in the surrounding tissue. Baseline pain thresholds were non
      significantly lower in neck pain patients compared to healthy controls and
      slightly increased immediately after cupping (p<0.05 compared to baseline close
      to the area of cupping in healthy subjects and on the foot in neck pain
      patients). After 280 min no more significant changes of pain thresholds were
      detected. CONCLUSIONS: Cupping induces >280 min lasting anaerobe metabolism in
      the subcutaneous tissue and increases immediate pressure pain thresholds in some
      areas.

PMID- 24559831
TI  - Is dietary supplementation more common among adults with psoriasis? Results from
      the National Health and Nutrition Examination Survey.
AB  - OBJECTIVES: Individuals with psoriasis are often unsatisfied with traditional
      medical treatments and may be more likely to use dietary supplements as
      alternative or complementary treatment. Limited data is available on the
      prevalence of dietary supplement use amongst individuals with psoriasis in the
      general population. The aim was to utilize a representative sample of the United
      States to estimate the prevalence of dietary supplement use among adults self
      reporting psoriasis. DESIGN AND SETTING: Cross-sectional data analysis from the
      2009 to 2010 National Health and Nutrition Examination Survey. Dietary
      supplementation over the past 30 days was ascertained and population weights were
      used to obtain estimates representative of the general population. Logistic
      regression was used to determine whether psoriasis was associated with higher
      odds of supplement use. RESULTS: This study consisted of 6211 participants aged
      >=20 years (representing 219 million Americans). Among the 184 participants
      reporting psoriasis (representing 6.9 million Americans), 53% reported using at
      least one dietary supplement, which was not different from participants without
      psoriasis (49.5%, P=0.416). Participants with psoriasis did not have higher odds
      of supplement use after adjusting for covariates. Multivitamin/mineral
      supplements were the most common dietary supplements used by participants with
      psoriasis (29.6%), and the most common reasons for taking them were to maintain
      and improve health. Only 12 supplements taken by participants with psoriasis were
      intended to improve skin health. CONCLUSIONS: Dietary supplementation over the
      past 30 days was reported by half of adults with psoriasis amongst the United
      States general population. Few individuals with psoriasis took dietary
      supplements specifically to improve skin health.

PMID- 24559832
TI  - The use of complementary and alternative medicine in patients with multiple
      sclerosis: a longitudinal study.
AB  - BACKGROUND: Complementary and alternative medicine (CAM) in chronic progressive
      diseases, like multiple sclerosis (MS), is highly prevalent. Up to now there are
      no satisfying longitudinal analysis about changes in using of CAM accompanied by
      influencing parameters like disease duration, stage of impairment or
      socioeconomic factors. This study captured the using of CAM of MS patients in
      combination with disease progression. METHODS: 119 Patients with MS were asked
      about CAM utilization, sociodemographic and disease factors within the context of
      a semistructured interview at an interval of seven years. The depressive status
      was ascertained with the Beck's Depression Inventory (BDI). Differences of users
      and non-users were checked with diverse statistical tests. RESULTS: Comparing
      both isolated measurements at second point less patients used CAM accompanied by
      worse socioeconomic situation and progression of the disease. Patients use CAM in
      a stage of illness, characterized by the Established Disability Status Scale
      (EDSS) between 3.5 and 4.0 points, signifying a transition from moderate to
      severe impairment, and a shorter duration of illness in comparison to non-users.
      Types of used CAM have been changed over seven years. Relaxation techniques and
      traditional Chinese medicine (TCM) are the favorite therapies at second
      measurement. DISCUSSION: As the key result of the study patients use CAM in an
      early stage of the disease. Their EDSS lies between 3.5 and 4.0 points and they
      suffer medial two years shorter from MS than non-users. CAM could be an important
      appliance to cope with the disease.

PMID- 24559833
TI  - Health benefits of qigong or tai chi for cancer patients: a systematic review and
      meta-analyses.
AB  - BACKGROUND: Cancer is a leading cause of death worldwide. Mind-body interventions
      are widely used by cancer patients to reduce symptoms and cope better with
      disease- and treatment-related symptoms. In the last decade, many clinical
      controlled trials of qigong/tai chi as a cancer treatment have emerged. This
      study aimed to quantitatively evaluate the effects of qigong/tai chi on the
      health-related outcomes of cancer patients. METHODS: Five databases (Medline,
      CINAHL, Scopus, the Cochrane Library, and the CAJ Full-text Database) were
      searched until June 30, 2013. Randomized controlled trials (RCTs) of qigong/tai
      chi as a treatment intervention for cancer patients were considered for
      inclusion. The primary outcome for this review was changes in quality of life
      (QOL) and other physical and psychological effects in cancer patients. The
      secondary outcome for this review was adverse events of the qigong/tai chi
      intervention. RESULTS: A total of 13 RCTs with 592 subjects were included in this
      review. Nine RCTs involving 499 subjects provided enough data to generate pooled
      estimates of effect size for health-related outcomes. For cancer-specific QOL,
      the pooled weighted mean difference (WMD) was 7.99 [95% confidence interval (CI):
      4.07, 11.91; Z score=4.00, p<0.0001]. The standardized mean differences (SMDs)
      for changes in depression and anxiety score were -0.69 (95% CI: -1.51, 0.14; Z
      score=1.64, p=0.10), and -0.93 (95% CI: -1.80, -0.06; Z score=2.09, p=0.04),
      respectively. The WMDs for changes in body mass index and body composition from
      baseline to 12 weeks follow-up were -1.66 (95% CI: -3.51, 0.19; Z score=1.76,
      p=0.08), and -0.67 (95% CI: -2.43, 1.09; Z score=0.75, p=0.45) respectively. The
      SMD for changes in the cortisol level was -0.37 (95% CI: -0.74, -0.00; Z
      score=1.97, p=0.05). CONCLUSION: This study found that qigong/tai chi had
      positive effects on the cancer-specific QOL, fatigue, immune function and
      cortisol level of cancer patients. However, these findings need to be interpreted
      cautiously due to the limited number of studies identified and high risk of bias
      in included trials. Further rigorous trials are needed to explore possible
      therapeutic effects of qigong/tai chi on cancer patients.

PMID- 24559834
TI  - Moxibustion for essential hypertension.
AB  - The objective of this review was to assess the current clinical evidence of
      moxibustion for essential hypertension (EH). 7 electronic databases were searched
      until March 2013. Randomized clinical trials testing moxibustion, or combined
      with antihypertensive drugs, against antihypertensive drugs alone were included.
      Study selection, data extraction, quality assessment, and data analyses were
      conducted according to the Cochrane standards. Finally, 5 randomized trials were
      included. The methodological quality of the included trials was evaluated as
      generally low. As compared to antihypertensive drugs, no positive results in BP
      (RR: 1.19 [0.50, 2.81]; P=0.70), was found about moxibustion. However, when
      combined with antihypertensive drugs, positive results in SBP (WMD: -9.57 [
      10.80, -8.34]; P<0.00001), DBP (WMD: -4.08 [-4.60, -3.56]; P<0.00001), and BP
      (RR: 3.35 [1.03, 10.89]; P=0.04) were found about moxibustion plus
      antihypertensive drugs. Most of the trials did not report adverse events, and the
      safety of moxibustion is still uncertain. Therefore, no confirm conclusion about
      the effectiveness and safety of moxibustion as adjunctive treatment for EH could
      be made. Rigorously designed trials are needed to confirm the evidence. 

PMID- 24559835
TI  - Data-driven modeling and predictive control for boiler-turbine unit using fuzzy
      clustering and subspace methods.
AB  - This paper develops a novel data-driven fuzzy modeling strategy and predictive
      controller for boiler-turbine unit using fuzzy clustering and subspace
      identification (SID) methods. To deal with the nonlinear behavior of boiler
      turbine unit, fuzzy clustering is used to provide an appropriate division of the
      operation region and develop the structure of the fuzzy model. Then by combining
      the input data with the corresponding fuzzy membership functions, the SID method
      is extended to extract the local state-space model parameters. Owing to the
      advantages of the both methods, the resulting fuzzy model can represent the
      boiler-turbine unit very closely, and a fuzzy model predictive controller is
      designed based on this model. As an alternative approach, a direct data-driven
      fuzzy predictive control is also developed following the same clustering and
      subspace methods, where intermediate subspace matrices developed during the
      identification procedure are utilized directly as the predictor. Simulation
      results show the advantages and effectiveness of the proposed approach. 

PMID- 24559836
TI  - Development of human natural killer cells and other innate lymphoid cells.
AB  - Innate lymphoid cells (ILC) have recently gained much attention in immunology.
      They represent a novel developmentally related family. Three distinct subsets
      have been identified on the basis of phenotypic and functional criteria and
      termed ILC1, ILC2, and ILC3. The available data suggest that ILC play an
      important role in innate defenses against different pathogens, in lymphoid
      organogenesis, and in tissue remodeling. All these aspects are relevant in
      hematopoietic stem cell transplantation (HSCT), particularly in the haplo-HSCT
      setting, in which donor NK cells are known to play a major therapeutic role,
      while the involvement of other ILC is still undefined. In this context, it has
      been postulated that all ILC share a common precursor expressing the ID2
      transcription factor. While the differentiation of human NK cells (belonging to
      ILC1) is now well characterized both in vitro and in vivo, limited information is
      available on the development of human ILC2 and ILC3 and of their relationships
      with NK cells. In this review, we will summarize the present knowledge on the
      developmental relationship among different ILC, with particular focus on early
      stages of NK cell differentiation, and their features shared with ILC2 and ILC3. 

PMID- 24559837
TI  - Ketogenic diet therapy can improve ACTH-resistant West syndrome in Japan.
AB  - PURPOSE: Ketogenic diet therapy (KD) has been used to treat children with
      refractory generalized epilepsy. We herein reported the efficacy of KD for West
      syndrome (WS) resistant to ACTH therapy. SUBJECTS: SUBJECTS, consisting of 6
      patients (3 boys, 3 girls) with WS who continued to have epileptic spasms (ES)
      and hypsarrhythmia, received KD because other treatments including ACTH therapy
      failed to control WS. METHODS: We retrospectively studied the clinical details of
      these patients and the efficacy of KD. RESULTS: The mean age at the onset of
      epilepsy was 4 months (0-15 months). The underlying etiology consisted of
      lissencephaly, Down's syndrome, and focal cortical dysplasia. Hypsarrhythmia
      disappeared 1 month after the introduction of KD in 5 patients. The disappearance
      of ES was achieved in 2 patients, the frequency of ES episodes was 80% less in 3,
      and no change was observed in 1. Psychomotor development was promoted in 5
      patients, along with improvements in ES and EEG. Gastrointestinal complications
      and lethargy, presumably caused by rapid ketosis, were reported as side effects
      in 3 patients during the first week of KD. Side effects including lethargy,
      anorexia, and unfavorable weight gain continued thereafter in these patients in
      spite of tolerance to KD. CONCLUSION: KD was effective for WS resistant to ACTH
      therapy, although gastrointestinal side effects should be considered when
      introducing KD to milk-fed infants.

PMID- 24559838
TI  - Pilocarpine-induced epilepsy is associated with actin cytoskeleton reorganization
      in the mossy fiber-CA3 synapses.
AB  - Dramatic structural changes have been demonstrated in the mossy fiber-CA3
      synapses in the post status epilepticus (SE) animals, suggesting a potential
      reorganization of filamentous actin (F-actin) network occurring in the
      hippocampus. However, until now the long-term effects of SE on the synaptic F
      actin have still not been reported. In this study, phalloidin labeling combined
      with confocal microscopy and protein analyses were adopted to investigate the
      effects of pilocarpine treatment on the F-actin in the C57BL/6 mice. As compared
      to the controls, there was ~ 43% reduction in F-actin density in the post SE
      mice. Quantitative analysis showed that the labeling density and the puncta
      number were significantly decreased after pilocarpine treatment (p<0.01, n=5 mice
      per group, Student's t-test). The puncta of F-actin in the post SE group tended
      to be highly clustered, while those in the controls were generally distributed
      evenly. The mean puncta size of F-actin puncta was 0.73+/-0.19MUm(2) (n=1102
      puncta from 5 SE mice) in the experimental group, significantly larger than that
      in the controls (0.51+/-0.10MUm(2), n=1983 puncta from 5 aged-matched control
      mice, p<0.01, Student's t-test). These observations were well consistent with the
      alterations of postsynaptic densities in the same region, revealed by
      immunostaining of PSD95, suggesting the reorganization of F-actin occurred mainly
      postsynaptically. Our results are indicative of important cytoskeletal changes in
      the mossy fiber-CA3 synapses after pilocarpine treatment, which may contribute to
      the excessive excitatory output in the hippocampal trisynaptic circuit. 

PMID- 24559839
TI  - Is there a clustering effect on electroencephalographic seizure localization?
AB  - Long-term video-EEG monitoring (LTM) is the gold standard for initial
      lateralization and localization of seizures in the workup for neurosurgical
      treatment of medically intractable epilepsy. Previous studies have yielded
      contradictory results as to whether seizures that occur in clusters tend to arise
      from the same brain region and may lead to the incorrect conclusion that seizures
      arise from a single focus. To determine whether seizure clustering affects
      localization in an LTM setting, the authors performed an observational study over
      6 years at a large regional epilepsy center on those undergoing LTM for seizure
      diagnosis, characterization, or presurgical workup. Excluding repeat studies and
      LTMs with generalized or nonepileptic seizures resulted in 479 monitorings with
      2774 focal seizures for analysis. Sequential pairs of consecutive focal seizures
      were classed as "concordant", "discordant," or "other," based on EEG
      localization. ANOVA analysis on the logarithm of the interseizure interval (LISI)
      among the three seizure pair groups showed no significant difference, p=0.47, nor
      did analysis defining concordance as lateralization to the same hemisphere
      (p=0.34). Analyses on subgroups with multifocal seizures, bilateral seizures, and
      extratemporal seizures all failed to show a significant difference. In
      conclusion, seizures have the same localizing value whether occurring in a
      cluster over a few hours or sporadically over a few days. This could potentially
      lead to shorter monitoring times. 

PMID- 24559840
TI  - Visualizing Meyer's loop: A comparison of deterministic and probabilistic
      tractography.
AB  - BACKGROUND: Diffusion tensor tractography of the anterior extent of the optic
      radiation - Meyer's loop - prior to temporal lobe resection (TLR) may reduce the
      risk for postoperative visual field defect. Currently there is no standardized
      way to perform tractography. OBJECTIVE: To visualize Meyer's loop using
      deterministic (DTG) and probabilistic tractography (PTG) at different probability
      levels, with the primary aim to explore possible differences between methods, and
      the secondary aim to explore anatomical accuracy. METHODS: Twenty-three diffusion
      tensor imaging exams (11 controls and 7 TLR-patients, pre- and post-surgical)
      were analyzed using DTG and PTG thresholded at probability levels 0.2%, 0.5%, 1%,
      5% and 10%. The distance from the tip of the temporal lobe to the anterior limit
      of Meyer's loop (TP-ML) was measured in 46 optic radiations. Differences in TP-ML
      between the methods were compared. Results of the control group were compared to
      dissection studies and to a histological atlas. RESULTS: For controls and
      patients together, there were statistically significant differences (p<0.01) for
      TP-ML between all methods thresholded at PTG <=1% compared to all methods
      thresholded at PTG >=5% and DTG. There were no statistically significant
      differences between PTG 0.2%, 0.5% and 1% or between PTG 5%, 10% and DTG. For the
      control group, PTG <=1% showed a closer match to dissection studies and PTG 1%
      showed the best match to histological tracings of Meyer's loop. CONCLUSIONS:
      Choice of tractography method affected the visualized location of Meyer's loop
      significantly in a heterogeneous, clinically relevant study group. For the
      controls, PTG at probability levels <=1% was a closer match to dissection
      studies. To determine the anterior extent of Meyer's loop, PTG is superior to DTG
      and the probability level of PTG matters.

PMID- 24559841
TI  - Vitamin K1 and 25(OH)D are independently and synergistically associated with a
      risk for hip fracture in an elderly population: a case control study.
AB  - BACKGROUND & AIMS: The incidence of hip fractures in Oslo is among the highest in
      the world. Vitamin D, as well as vitamin K, may play an important role in bone
      metabolism. We examined if vitamin K1 and 25(OH)D were associated with an
      increased risk of hip fracture, and whether the possible synergistic effect of
      these two micronutrients is mediated through bone turnover markers. METHODS:
      Blood was drawn for vitamin K1, 25(OH)D, and the bone turnover marker osteocalcin
      upon admission for hip fracture and in healthy controls. RESULTS: Vitamin K1 and
      25(OH)D were independently associated with a risk of hip fracture. The adjusted
      odds ratio (95% CI) per ng/ml increase in vitamin K1 was 0.07 (0.02-0.32), and
      that per nmol/L increase in 25(OH)D was 0.96 (0.95-0.98). There was a significant
      interaction between 25(OH)D and vitamin K1 (p < 0.001), and a significant
      correlation between total osteocalcin and vitamin K1 and 25(OH)D (rho = 0.18, p =
      0.01; rho = 0.20, p = 0.01, respectively). CONCLUSIONS: Vitamin K1 and 25(OH)D
      are lower in hip fracture patients compared with controls. Vitamin K1 and 25(OH)D
      are independently and synergistically associated with the risk of hip fracture
      when adjusting for confounders. Intervention studies should include both
      vitamins.

PMID- 24559842
TI  - Common single nucleotide polymorphisms in the FNDC5 gene are associated with
      glucose metabolism but do not affect serum irisin levels in Japanese men with low
      fitness levels.
AB  - OBJECTIVE: This cross-sectional study analyzed the association of serum irisin
      concentrations with cardiorespiratory fitness levels and common single nucleotide
      polymorphisms (SNPs) in the FNDC5 gene and examined the relationships between
      cardiorespiratory fitness levels, common SNPs in FNDC5, and glucose metabolism.
      MATERIALS/METHODS: Cardiorespiratory fitness was assessed by measuring peak
      oxygen uptake (VO2peak) and serum irisin levels by ELISA in 163 Japanese men
      (age, 21-79years). Subjects were divided into low- and high-fitness groups within
      each age group according to the median VO2peak value. Common SNPs (rs3480 and
      rs16835198) of the FNDC5 gene were genotyped with the TaqMan assay. Glucose
      metabolism was evaluated by measuring HbA1c, fasting plasma glucose (FPG),
      insulin levels, and HOMA-IR. RESULTS: Serum irisin levels were negatively
      correlated with age (p<0.001) and not associated with the VO2peak or HOMA-IR. In
      the low-fitness group, SNP analysis revealed that subjects with the rs3480 AG and
      GG genotypes had higher levels of insulin and HOMA-IR than those with the AA
      genotype (p<0.01; no significant difference was observed in the high-fitness
      group). The GG genotypes of rs16835198 were associated with increased HbA1c and
      FPG in the low-fitness group only (p<0.05). SNPs and both fitness groups were not
      associated with serum irisin levels. CONCLUSIONS: In Japanese men,
      cardiorespiratory fitness levels and common SNPs in FNDC5 are not associated with
      circulating irisin levels, whereas high cardiorespiratory fitness abolishes the
      association between the rs3480 and rs16835198 SNPs and glucose metabolism
      independent of serum irisin levels.

PMID- 24559844
TI  - Scopoletin prevents alcohol-induced hepatic lipid accumulation by modulating the
      AMPK-SREBP pathway in diet-induced obese mice.
AB  - OBJECTIVE: This study investigated the effects of scopoletin on alcohol-induced
      hepatic lipid accumulation in diet-induced obese mice and its mechanism.
      MATERIAL/METHODS: Alcohol (25% v/v, 5g/kg body weight) was orally administered
      once a day for 6 weeks to mice fed with a high-fat diet (35%kcal) with or without
      scopoletin (0.05%, wt/wt). RESULTS: Scopoletin reduced plasma acetaldehyde, fatty
      acid, total cholesterol, triglyceride and insulin levels, hepatic lipid and
      droplets and fasting blood glucose levels that were increased by alcohol.
      Scopoletin significantly activated hepatic AMPK and inhibited ACC and SREBP-1c
      and the activities of lipogenic enzymes, such as FAS, PAP and G6PD compared to
      the alcohol control group. Moreover, scopoletin significantly inhibited hepatic
      CYP2E1 activity and protein levels but elevated the activities of SOD, CAT, GSH
      Px and GST and the levels of GSH compared to the alcohol control group. The
      hepatic lipid peroxide level was significantly lowered by scopoletin
      supplementation in alcohol-administered obese mice. CONCLUSIONS: Taken together,
      these results suggested that scopoletin can ameliorate alcohol-induced hepatic
      lipid accumulation by modulating AMPK-SREBP pathway-mediated lipogenesis in mice
      fed a high-fat diet.

PMID- 24559843
TI  - Impact of baseline physical activity and diet behavior on metabolic syndrome in a
      pharmaceutical trial: results from NAVIGATOR.
AB  - OBJECTIVE: The cardiometabolic risk cluster metabolic syndrome (MS) includes >=3
      of elevated fasting glucose, hypertension, elevated triglycerides, reduced high
      density lipoprotein cholesterol (HDL-c), and increased waist circumference. Each
      can be affected by physical activity and diet. Our objective was to determine
      whether determine whether baseline physical activity and/or diet behavior impact
      MS in the course of a large pharmaceutical trial. MATERIALS/METHODS: This was an
      observational study from NAVIGATOR, a double-blind, randomized (nateglinide,
      valsartan, both, or placebo), controlled trial between 2002 and 2004. We studied
      data from persons (n=9306) with impaired glucose tolerance and cardiovascular
      disease (CVD) or CVD risk factors; 7118 with pedometer data were included in this
      analysis. Physical activity was assessed with 7-day pedometer records; diet
      behavior was self-reported on a 6-item survey. An MS score (MSSc) was calculated
      using the sum of each MS component, centered around the Adult Treatment Panel III
      threshold, and standardized according to sample standard deviation. Excepting HDL
      c, assessed at baseline and year 3, MS components were assessed yearly. Follow-up
      averaged 6 years. RESULTS: For every 2000-step increase in average daily steps,
      there was an associated reduction in average MSSc of 0.29 (95% CI (-)0.33 to (
      )0.25). For each diet behavior endorsed, there was an associated reduction in
      average MSSc of 0.05 (95% CI (-)0.08 to (-)0.01). Accounting for the effects of
      pedometer steps and diet behavior together had minimal impact on parameter
      estimates with no significant interaction. Relations were independent of age,
      sex, race, region, smoking, family history of diabetes, and use of nateglinide,
      valsartan, aspirin, antihypertensive, and lipid-lowering agent. CONCLUSIONS:
      Baseline physical activity and diet behavior were associated independently with
      reductions in MSSc such that increased attention to these lifestyle elements
      provides cardiometabolic benefits. Thus, given the potential to impact outcomes,
      assessment of physical activity and diet should be performed in pharmacologic
      trials targeting cardiometabolic risk.

PMID- 24559847
TI  - Prospective comparison of speckle tracking longitudinal bidimensional strain
      between two vendors.
AB  - BACKGROUND: Speckle tracking is a relatively new, largely angle-independent
      technique used for the evaluation of myocardial longitudinal strain (LS).
      However, significant differences have been reported between LS values obtained by
      speckle tracking with the first generation of software products. AIMS: To compare
      LS values obtained with the most recently released equipment from two
      manufacturers. METHODS: Systematic scanning with head-to-head acquisition with no
      modification of the patient's position was performed in 64 patients with
      equipment from two different manufacturers, with subsequent off-line post
      processing for speckle tracking LS assessment (Philips QLAB 9.0 and General
      Electric [GE] EchoPAC BT12). The interobserver variability of each software
      product was tested on a randomly selected set of 20 echocardiograms from the
      study population. RESULTS: GE and Philips interobserver coefficients of variation
      (CVs) for global LS (GLS) were 6.63% and 5.87%, respectively, indicating good
      reproducibility. Reproducibility was very variable for regional and segmental LS
      values, with CVs ranging from 7.58% to 49.21% with both software products. The
      concordance correlation coefficient (CCC) between GLS values was high at 0.95,
      indicating substantial agreement between the two methods. While good agreement
      was observed between midwall and apical regional strains with the two software
      products, basal regional strains were poorly correlated. The agreement between
      the two software products at a segmental level was very variable; the highest
      correlation was obtained for the apical cap (CCC 0.90) and the poorest for basal
      segments (CCC range 0.31-0.56). CONCLUSIONS: A high level of agreement and
      reproducibility for global but not for basal regional or segmental LS was found
      with two vendor-dependent software products. This finding may help to reinforce
      clinical acceptance of GLS in everyday clinical practice.

PMID- 24559848
TI  - Heart failure with preserved ejection fraction: looking for new pieces of a
      complex puzzle.

PMID- 24559845
TI  - The many roles of PGC-1alpha in muscle--recent developments.
AB  - Skeletal muscle is the largest organ in the body and contributes to innumerable
      aspects of organismal biology. Muscle dysfunction engenders numerous diseases,
      including diabetes, cachexia, and sarcopenia. At the same time, skeletal muscle
      is also the main engine of exercise, one of the most efficacious interventions
      for prevention and treatment of a wide variety of diseases. The transcriptional
      coactivator PGC-1alpha has emerged as a key driver of metabolic programming in
      skeletal muscle, both in health and in disease. We review here the many aspects
      of PGC-1alpha function in skeletal muscle, with a focus on recent developments.

PMID- 24559846
TI  - Consuming a balanced high fat diet for 16 weeks improves body composition,
      inflammation and vascular function parameters in obese premenopausal women.
AB  - OBJECTIVE: Inflammation, insulin resistance and vascular dysfunction characterize
      obesity and predict development of cardiovascular disease (CVD). Although women
      experience CVD events at an older age, vascular dysfunction is evident 10years
      prior to coronary artery disease. Questions remain whether replacing SFA entirely
      with MUFA or PUFA is the optimal approach for cardiometabolic benefits. This
      study tested the hypotheses that: a) body composition, inflammation and vascular
      function would improve with a high fat diet (HFD) when type of fat is balanced as
      1/3 SFA, 1/3 MUFA and 1/3 PUFA; and b) body composition, inflammation and
      vascular function would improve more when balanced HFD is supplemented with 18C
      fatty acids, in proportion to the degree of 18C unsaturation. METHODS: Obese
      premenopausal women were stabilized on balanced HFD and randomized to consume
      9g/d of encapsulated stearate (18:0), oleate (18:1), linoleate (18:2) or placebo.
      RESULTS: Significant improvements occurred in fat oxidation rate (?6%), body
      composition (%fat: ?2.5+/-2.1%; %lean: ?2.5+/-2.1%), inflammation (? IL-1alpha,
      IL-1beta, 1L-12, Il-17, IFNgamma, TNFalpha, TNFbeta) and vascular function (?BP,
      ?PAI-1, ?tPA activity). When compared to HFD+placebo, HFD+stearate had the
      greatest effect on reducing IFNgamma (?74%) and HFD+linoleate had the greatest
      effect on reducing PAI-1 (?31%). CONCLUSIONS: Balancing the type of dietary fat
      consumed (SFA/MUFA/PUFA) is a feasible strategy to positively affect markers of
      CVD risk. Moreover, reductions in inflammatory molecules involved in vascular
      function might be enhanced when intake of certain 18C fatty acids is
      supplemented. Long term effects need to be determined for this approach.

PMID- 24559850
TI  - Decreased serum levels of adiponectin in adult attention deficit hyperactivity
      disorder.
AB  - The main aim of this study was to investigate serum levels of adiponectin in
      adult patients with attention deficit hyperactivity disorder (ADHD). The second
      objective was to examine the effects of rare missense mutations in T-cadherin, an
      adiponectin receptor encoded by the ADHD candidate gene CDH13, on serum
      adiponectin levels. Total and high molecular weight (HMW) adiponectin levels were
      measured by an enzyme-linked immunosorbent assay in 44 patients and 29 controls.
      We found decreased serum adiponectin levels in ADHD patients. In a logistic
      regression model, adjusting for confounding by age, body mass index, and gender,
      HMW adiponectin and its ratio to total adiponectin were significantly associated
      with ADHD. In partial correlations, HMW adiponectin and its ratio to total
      adiponectin were significantly inversely correlated with self-reported
      psychiatric symptomatology. A non significant trend for higher levels of total
      adiponectin was observed in patients carrying CDH13 missense mutations compared
      to patients with wild type CDH13. The association of CDH13 mutations with
      adiponectin levels should be investigated in larger studies. This study shows
      that ADHD patients have decreased serum adiponectin levels, which are inversely
      correlated to psychiatric symptoms, suggesting a possible involvement of
      adiponectin, in particular the HMW form, in the pathophysiology of ADHD. 

PMID- 24559849
TI  - Gonorrhoea.
AB  - INTRODUCTION: In 2012, the diagnosis rates for gonorrhoea among adults aged 20 to
      24 years in the UK were 249 per 100,000 for men and 140 per 100,000 for women.
      Resistance to one or more antimicrobial agent is reported in more than one
      quarter of isolates. Co-infection with Chlamydia trachomatis is reported in 10%
      to 40% of people with gonorrhoea in the US and UK. METHODS AND OUTCOMES: We
      conducted a systematic review and aimed to answer the following clinical
      questions: What are the effects of treatments for uncomplicated infections in men
      and non-pregnant women, and in pregnant women? What are the effects of treatments
      for disseminated gonococcal infection? What are the effects of dual treatment for
      gonorrhoea and chlamydia infection? We searched: Medline, Embase, The Cochrane
      Library, and other important databases up to September 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 7
      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: antibiotic regimens (dual treatment, multiple dose, single dose).

PMID- 24559851
TI  - Lower health related quality of life in U.S. military personnel is associated
      with service-related disorders and inflammation.
AB  - Military personnel who have combat exposures are at increased risk for the
      service-related disorders of post-traumatic stress disorder (PTSD), depression,
      sleep disturbances and decreased health related quality of life (HRQOL). Those
      with a traumatic brain injury (TBI) are at even greater risk. Inflammation is
      associated with these disorders and may underlie the risk for health declines. We
      evaluated 110 recently deployed, military personnel presenting with sleep
      disturbances for service-related disorders (TBI, PTSD, and depression) as well as
      HRQOL. ANOVA models were used to examine differences among military personnel
      with two or more service-related disorders (high comorbid group), or one or no
      disorders (low comorbid group). Logistic regression models were used to determine
      associations among interleukin-6 (IL-6) to HRQOL and service-related disorders.
      Approximately one-third of the sample had two or more service-related disorders.
      HRQOL was lower and IL-6 concentrations were higher in military personnel with
      PTSD or depression, with the most profound differences in those with more service
      related disorders, regardless of sleep disorder. Having symptoms of depression
      and PTSD resulted in a 3.5-fold risk to be in the lower quartile of HRQOL and the
      highest quartile of IL-6. In a linear regression model, 41% of the relationship
      between HRQOL and IL-6 concentrations was mediated by PTSD and depression.
      Military personnel with PTSD and depression are at high risk for lower HRQOL, and
      higher IL-6 concentrations. Comprehensive treatment is required to address co
      occurring service-related disorders in military personnel to promote health and
      well-being. 

PMID- 24559852
TI  - A nomogram to predict Gleason sum upgrading of clinically diagnosed localized
      prostate cancer among Chinese patients.
AB  - Although several models have been developed to predict the probability of Gleason
      sum upgrading between biopsy and radical prostatectomy specimens, most of these
      models are restricted to prostate-specific antigen screening-detected prostate
      cancer. This study aimed to build a nomogram for the prediction of Gleason sum
      upgrading in clinically diagnosed prostate cancer. The study cohort comprised 269
      Chinese prostate cancer patients who underwent prostate biopsy with a minimum of
      10 cores and were subsequently treated with radical prostatectomy. Of all
      included patients, 220 (81.8%) were referred with clinical symptoms. The prostate
      specific antigen level, primary and secondary biopsy Gleason scores, and clinical
      T category were used in a multivariate logistic regression model to predict the
      probability of Gleason sum upgrading. The developed nomogram was validated
      internally. Gleason sum upgrading was observed in 90 (33.5%) patients. Our
      nomogram showed a bootstrap-corrected concordance index of 0.789 and good
      calibration using 4 readily available variables. The nomogram also demonstrated
      satisfactory statistical performance for predicting significant upgrading.
      External validation of the nomogram published by Chun et al. in our cohort showed
      a marked discordance between the observed and predicted probabilities of Gleason
      sum upgrading. In summary, a new nomogram to predict Gleason sum upgrading in
      clinically diagnosed prostate cancer was developed, and it demonstrated good
      statistical performance upon internal validation. 

PMID- 24559853
TI  - Maximum standardized uptake value on PET/CT in preoperative assessment of lymph
      node metastasis from thoracic esophageal squamous cell carcinoma.
AB  - The presence of lymph node metastasis is an important prognostic factor for
      patients with esophageal cancer. Accurate assessment of lymph nodes in thoracic
      esophageal carcinoma is essential for selecting appropriate treatment and
      forecasting disease progression. Positron emission tomography combined with
      computed tomography (PET/CT) is becoming an important tool in the workup of
      esophageal carcinoma. Here, we evaluated the effectiveness of the maximum
      standardized uptake value (SUVmax) in assessing lymph node metastasis in
      esophageal squamous cell carcinoma (ESCC) prior to surgery. Fifty-nine surgical
      patients with pathologically confirmed thoracic ESCC were retrospectively
      studied. These patients underwent radical esophagectomy with pathologic
      evaluation of lymph nodes. They all had (18)F-FDG PET/CT scans in their
      preoperative staging procedures. None had a prior history of cancer. The
      pathologic status and PET/CT SUVmax of lymph nodes were collected to calculate
      the receiver operating characteristic (ROC) curve and to determine the best
      cutoff value of the PET/CT SUVmax to distinguish benign from malignant lymph
      nodes. Lymph node data from 27 others were used for the validation. A total of
      323 lymph nodes including 39 metastatic lymph nodes were evaluated in the
      training cohort, and 117 lymph nodes including 32 metastatic lymph nodes were
      evaluated in the validation cohort. The cutoff point of the SUVmax for lymph
      nodes was 4.1, as calculated by ROC curve (sensitivity, 80%; specificity, 92%;
      accuracy, 90%). When this cutoff value was applied to the validation cohort, a
      sensitivity, a specificity, and an accuracy of 81%, 88%, and 86%, respectively,
      were obtained. These results suggest that the SUVmax of lymph nodes predicts
      malignancy. Indeed, when an SUVmax of 4.1 was used instead of 2.5, FDG-PET/CT was
      more accurate in assessing nodal metastasis.

PMID- 24559854
TI  - External validation of nomograms for predicting cancer-specific mortality in
      penile cancer patients treated with definitive surgery.
AB  - Using a population-based cancer registry, Thuret et al. developed 3 nomograms for
      estimating cancer-specific mortality in men with penile squamous cell carcinoma.
      In the initial cohort, only 23.0% of the patients were treated with inguinal
      lymphadenectomy and had pN stage. To generalize the prediction models in clinical
      practice, we evaluated the performance of the 3 nomograms in a series of penile
      cancer patients who were treated with definitive surgery. Clinicopathologic
      information was obtained from 160 M0 penile cancer patients who underwent primary
      tumor excision and regional lymphadenectomy between 1990 and 2008. The predicted
      probabilities of cancer-specific mortality were calculated from 3 nomograms that
      were based on different disease stage definitions and tumor grade.
      Discrimination, calibration, and clinical usefulness were assessed to compare
      model performance. The discrimination ability was similar in nomograms using the
      TNM classification or American Joint Committee on Cancer staging (Harrell's
      concordance index = 0.817 and 0.832, respectively), whereas it was inferior for
      the Surveillance, Epidemiology and End Results staging (Harrell's concordance
      index = 0.728). Better agreement with the observed cancer-specific mortality was
      shown for the model consisting of TNM classification and tumor grade, which also
      achieved favorable clinical net benefit, with a threshold probability in the
      range of 0 to 42%. The nomogram consisting of TNM classification and tumor
      grading was shown to have better performance for predicting cancer-specific
      mortality in penile cancer patients who underwent definitive surgery. Our data
      support the integration of this model in decision-making and trial design. 

PMID- 24559855
TI  - Supplementation of a dairy drink enriched with milk phospholipids in patients
      with atopic dermatitis - a double-blind, placebo-controlled, randomized, cross
      over study.
AB  - BACKGROUND & AIMS: Reduced epidermal ceramide content may lead to an impaired
      skin barrier in atopic dermatitis. Plasma concentration of the ceramide precursor
      sphingomyelin increases after milk-fat consumption due to affected lipoprotein
      metabolism, although sphingomyelin, a main component of milk phospholipids, might
      also directly influence plasma sphingomyelin levels. The aim was to determine
      whether supplementation of a dairy drink with milk phospholipids improves skin
      parameters and influences plasma lipid profile. METHODS: In a double-blind cross
      over study, 39 patients were randomized into 2 groups and daily received
      phospholipid milk (3 g phospholipids ? 0.75 g sphingomyelin) or normal whole milk
      as placebo control for 6 weeks. SCORAD indices, serum immune and plasma lipid
      parameters were determined. RESULTS: SCORAD indices did not differ between groups
      following control and phospholipid milk supplementation (control milk: 10.9 +/-
      5.9 vs. phospholipid milk: 11.7 +/- 6.9, P = 0.416), but were significantly
      decreased compared to baseline (baseline: 15.6 +/- 8.8, P < 0.05). Plasma
      sphingomyelin proportions were also similar after the treatments (control milk:
      27.5 +/- 2.3 vs. phospholipid milk: 27.4 +/- 2.6% of total phospholipids, P =
      0.894), but were significantly increased compared to baseline (20.7 +/- 2.4% of
      total phospholipids, P < 0.05). CONCLUSIONS: Supplementation of a dairy drink
      with milk phospholipids has no beneficial effect on skin parameters compared to
      consumption of whole milk in patients with atopic dermatitis. To elucidate an
      impact of the plasma sphingomyelin proportion on skin conditions, further studies
      are necessary. Clinical trial ID: Registered under ClinicalTrials.gov. Identifier
      no. NCT01326520.

PMID- 24559856
TI  - Adherence to the Mediterranean diet is inversely related to binge eating disorder
      in patients seeking a weight loss program.
AB  - BACKGROUND & AIM: The key factors influencing the development of Binge Eating
      Disorder (BED) are not well known. Adherence to the Mediterranean diet (MD) has
      been suspected to reduce the risk of several mental illnesses such as depression
      and anxiety. There are no existing studies that have examined the relationships
      between BED and MD. METHODS: Cross-sectional study of 1472 participants (71.3%
      women; mean age: 44.8 +/- 12.7) at high risk of BED. A MD score (MED-score) was
      derived from a validated food frequency questionnaire and BED by Binge Eating
      Scale questionnaire (BES). Body mass index, waist circumference and total body
      fat (%) were assessed by anthropometric measurements. RESULTS: 376 (25.5%) cases
      of self reported BED were identified. 11.1% of participants had a good adherence
      to MD (MED-score >= 9). After adjustments for age, gender, nutritional status,
      education, and physical activity level, high MED-score was associated with lower
      odds for BED (odds ratios and 95% confidence intervals of a BED disorder for
      successive levels of MED-score were 1 (reference), 0.77 (0.44, 1.36), 0.66 (0.37,
      1.15), 0.50 (0.26, 0.96), and 0.45 (0.22, 0.55) (P for trend: <0.01). Olive oil
      and nut consumption were associated with low risk of BED development whereas
      butter, cream, sweets and commercial bakery/sweets/cakes consumption increased
      the risk. We did not find a cumulative effect of depression and anxiety on MED
      score in binge eaters. CONCLUSIONS: These results demonstrate an inverse
      association between MD and the development of BED in a clinical setting among
      subjects at risk of BED. Therefore, we should be cautious about generalizing the
      results to the whole population, although reverse causality and confounding
      cannot be excluded as explanation. Further prospective studies are warranted.

PMID- 24559857
TI  - Clinical inertia, uncertainty and individualized guidelines.
AB  - Doctors often do not follow the guidelines of good practice based on evidence
      based medicine, and this "clinical inertia" may represent an impediment to
      efficient care. The aims of this article are as follows: 1) to demonstrate that
      this phenomenon is often the consequence of a discrepancy between the technical
      rationality of evidence-based medicine and the modes of reasoning of physicians
      practiced in "real-life", which is marked by uncertainty and risk; 2) to
      investigate in this context the meaning of the recent, somewhat paradoxical,
      concept of "individualized guidelines"; and 3) to revisit the real, essentially
      pedagogical, place of guidelines in medical practice. 

PMID- 24559858
TI  - Effect of Botox injection at the bladder neck in boys with bladder dysfunction
      after valve ablation.
AB  - OBJECTIVE: After posterior urethral valve ablation, some boys are still have a
      hostile bladder. We conducted a prospective randomized study to determine if
      Botox injection at the bladder neck will help improve vesical dysfunction in this
      subgroup of boys or not. PATIENTS AND METHODS: Twenty boys with history of
      posterior urethral valve ablation and severe bladder dysfunction with a mean age
      of 16 months were studied. Cases were further randomized into two groups. Group I
      (study group) had endoscopic injection of a single dose of 100 IU of Botox into
      the hypertrophied bladder neck at 3, 6, and 9 o'clock. Group II (control group)
      patients with the same parameters had urethroscopy to exclude residual valves.
      Both groups had the standard conservative treatment. Cases were followed after 6
      months of initiating the management protocol. This includes laboratory studies
      (urine culture and sensitivity, blood urea nitrogen, serum creatinine),
      ultrasound of the urinary tract. Voiding cysto-urethrogram and urodynamic study
      (pressure flow study). RESULTS: There was no statistical difference in both
      groups regarding rate of urinary tract infection, improvement of hydronephrosis,
      resolution of vesico-ureteral reflux, creatinine level at the start or at the end
      of the study. Urodynamic parameters revealed an increase in cystometric capacity
      in both groups at the end of the study but without statistical difference. The
      mean voiding pressure reduced significantly in both groups but without
      statistical difference. CONCLUSIONS: Temporarily abolishing the effect of bladder
      neck by Botox injection does not seem to improve the outcome of those boys who
      had a severe voiding dysfunction after valve ablation.

PMID- 24559859
TI  - Commentary to 'Upper tract changes in patients with neurogenic bladder and
      sustained pressures >40 cm following bladder neck surgery without augmentation'.

PMID- 24559860
TI  - [Primary synovial sarcoma of the parotid gland].
AB  - INTRODUCTION: Synovial sarcoma is a malignant soft tissue neoplasm which occurs
      most of the time in teenagers and young adults. Facial, and especially parotid
      gland localization, is very uncommon. CASE REPORT: A 15-year-old male patient,
      with no prior history, was hospitalized for swelling in the left parotid area
      noted 5 months before. The mass was painful and there was no facial paralysis. A
      CT scan revealed a tumoral process of mixed density in the left parotid gland.
      The thorax and abdominal CT scan was normal. The patient was initially treated by
      surgery and adjuvant chemotherapy. He died, 8 months after this multimodal
      therapy. DISCUSSION: Five percent of salivary gland primitive tumors are of
      mesenchymatous origin, 0.3 to 1.5% of which are sarcomas. The diagnosis of
      parotid gland synovial sarcoma is confirmed by immune-histochemistry and
      cytogenetic tests. Surgery combined to radiotherapy seems to be the best
      treatment.

PMID- 24559862
TI  - Barriers to sexual and reproductive health care among widows in Nepal.
AB  - OBJECTIVE: To investigate how the social status of high-caste Nepali widows of
      reproductive age impacts their sexual and reproductive health care. METHODS:
      Twenty-one in-depth interviews and 1 focus group (n=6) were conducted between
      September and November 2012 in the Kathmandu, Kavre, and Chitwan districts of
      Nepal. Participants were members of Women for Human Rights, Single Women Group.
      Interviews and the focus group with widows followed a semi-structured interview
      guide designed to elicit information on sexual and reproductive health problems,
      knowledge about them, and barriers to care. Two researchers used inductive and
      deductive coding to analyze transcripts for themes using ATLAS.ti. RESULTS:
      Widows reported facing substantial obstacles to accessing sexual and reproductive
      health care. Widows suspected of having sexual and reproductive health problems,
      or who discussed or tried to access these services, could be ostracized by their
      families and experience severe economic and psychological consequences.
      Additionally, widows feared discrimination, lack of confidentiality, and sexual
      harassment by male providers if their status was known. These barriers appeared
      to stem from the perception that sexual relationships are necessary for widows to
      require care for gynecologic problems. CONCLUSION: Widows expressed a need for
      sexual and reproductive health care and described cultural and systematic
      barriers to accessing this care; these barriers need to be addressed.

PMID- 24559863
TI  - Diagnostic utility of CD4%:CD8 low% T-lymphocyte ratio to differentiate feline
      immunodeficiency virus (FIV)-infected from FIV-vaccinated cats.
AB  - Antibody testing based on individual risk assessments is recommended to determine
      feline immunodeficiency virus (FIV) status, but ELISA and Western blot tests
      cannot distinguish between anti-FIV antibodies produced in response to natural
      infection and those produced in response to FIV vaccination. The aim of this
      cross-sectional study was to test the hypothesis that FIV-infected cats could be
      differentiated from FIV-vaccinated uninfected cats using lymphocyte subset
      results, specifically the CD4%:CD8(low)% T-lymphocyte ratio. Comparisons of the
      CD4%:CD8(low)% T-lymphocyte ratio were made among the following four groups:
      Group 1 - FIV-infected cats (n=61; FIV-antibody positive by ELISA and FIV PCR
      positive); Group 2 - FIV-uninfected cats (n=96; FIV-antibody negative by ELISA);
      Group 3 - FIV-vaccinated uninfected cats (n=31; FIV-antibody negative by ELISA
      before being vaccinated against FIV, after which they tested FIV ELISA positive);
      and Group 4 - FIV-uninfected but under chronic/active antigenic stimulation
      (n=16; FIV-antibody negative by ELISA; all had active clinical signs of either
      upper respiratory tract disease or gingival disease for >= 21 days). The median
      CD4%:CD8(low)% T-lymphocyte ratio was lower in Group 1 (1.39) than in each of the
      other three groups (Group 2 - 9.77, Group 3 - 9.72, Group 4 - 5.64; P<0.05). The
      CD4%:CD8(low)% T-lymphocyte ratio was also the most effective discriminator
      between FIV-infected cats and the other three groups, and areas under ROC curves
      ranged from 0.91 (compared with Group 4) to 0.96 (compared with Group 3).
      CD4%:CD8(low)% shows promise as an effective test to differentiate between FIV
      infected cats and FIV-vaccinated uninfected cats. 

PMID- 24559864
TI  - Underestimated role of MRI in EAU guidelines on prostate cancer.

PMID- 24559861
TI  - HIV-1 uncoating: connection to nuclear entry and regulation by host proteins.
AB  - The RNA genome of human immunodeficiency virus type 1 (HIV-1) is enclosed by a
      capsid shell that dissociates within the cell in a multistep process known as
      uncoating, which influences completion of reverse transcription of the viral
      genome. Double-stranded viral DNA is imported into the nucleus for integration
      into the host genome, a hallmark of retroviral infection. Reverse transcription,
      nuclear entry, and integration are coordinated by a capsid uncoating process that
      is regulated by cellular proteins. Although uncoating is not well understood,
      recent studies have revealed insights into the process, particularly with respect
      to nuclear import pathways and protection of the viral genome from DNA sensors.
      Understanding uncoating will be valuable toward developing novel antiretroviral
      therapies for HIV-infected individuals. 

PMID- 24559865
TI  - Dependence of residual dipolar couplings on foot angle in (1)H MR spectra from
      skeletal muscle.
AB  - Foot dorsi and plantar flexion affects the pennation angle of skeletal muscle
      fibers and changes the fiber direction with respect to the main magnetic field,
      thereby affecting MR spectrum of the muscle. In order to analyze the effect that
      foot flexion has on the MR spectrum, tibialis anterior (TA) and soleus muscles
      were studied in humans and rats. Localized MRS was performed at different foot
      angles in clinical and pre-clinical settings using a 3T MRI/MRS GE Excite HD and
      7T Bruker Clinscan scanner, respectively. In this study we show the effect of
      foot angle variation on total Creatine (tCr) resonance of (1)H spectrum at 3.03
      and 3.93ppm for TA and soleus muscles. In addition to this, we observe a 4-line
      splitting pattern for methylene resonance of tCr in the rat TA spectrum for a
      specific foot angle. This observation is attributed to the individual splitting
      of creatine and phosphocreatine of the tCr signal. Novel hydrogel application is
      demonstrated and used to support our in vivo observations and for the first time
      splitting of individual resonances of Cr and PCr has been shown in an in vitro
      set-up. 

PMID- 24559866
TI  - Minocycline is a reliable and effective oral option to treat meticillin-resistant
      Staphylococcus aureus skin and soft-tissue infections, including doxycycline
      treatment failures.

PMID- 24559867
TI  - Development of novel silicon-containing inverse agonists of retinoic acid
      receptor-related orphan receptors.
AB  - Retinoic acid receptor (RAR)-related orphan receptors (RORs) regulate a variety
      of physiological processes, including hepatic gluconeogenesis, lipid metabolism,
      circadian rhythm and immune function. The RAR agonist: all-trans retinoic acid
      was reported to be an RORbeta inverse agonist, but no information is available
      regarding ROR activity of its synthetic analogue Am580. Therefore, we screened
      Am580 and some related tetramethyltetrahydronaphthalene derivatives and carried
      out structural development studies, including substitution of carbon atoms with
      silicon, with the aim of creating a potent ROR transcriptional inhibitor. The
      phenyl amide disila compound 22 showed the most potent ROR-inhibitory activity
      among the compounds examined. Its activity towards RORalpha, RORbeta and RORgamma
      was increased compared to that of Am580. The IC50 values for RORalpha, RORbeta
      and RORgamma are 1.3, >10 and 4.5 MUM, respectively.

PMID- 24559868
TI  - The foot and ankle examination.
AB  - Most foot and ankle disorders can be diagnosed after a proper history and
      clinical examination and can be effectively managed in a primary care setting. It
      is important to assess the entirety of patient disorders that present as they can
      be multifactorial in cause. A broad differential should include disorders of
      bones, joints, muscles, neurovasculature, and surrounding soft tissue structures.
      Physical examination should be thorough and focused on inspection, palpation,
      range of motion, and appropriate special tests when applicable. This article
      highlights some of the salient features of the foot and ankle examination and
      diagnostic considerations. 

PMID- 24559869
TI  - Gait: the role of the ankle and foot in walking.
AB  - Evaluation of gait and its associated deviations from normal requires an in-depth
      evaluation of the patient and an appreciation for the complexity of the task.
      Understanding gait starts with an appreciation of the basic determinants of gait.
      Foot drop is a common gait deviation. Functionally, a foot drop results in a long
      limb. This will result in alterations of the gait cycle during swing phase. The
      common compensations for a foot drop include steppage gait, circumduction, and a
      persistently abducted limb. Noninterventional options for management of common
      gait deviations secondary to ankle/foot dysfunction present challenges. 

PMID- 24559870
TI  - Nail and skin disorders of the foot.
AB  - Disorders of the dermis and the nails on the feet are common. Despite the
      simplicity of the skin and nail disorders of the foot, they can be debilitating
      and impact the patient's ability to ambulate and perform activities of daily
      living. Diagnosis in most cases is confirmed on physical examination alone.
      Diligent care of skin and nail disorders can prevent further pathology involving
      the deeper structures of the foot and allow the patient to fully participate in
      their usual activities. 

PMID- 24559871
TI  - Hallux valgus.
AB  - Hallux valgus is a common foot problem whose cause and progression is
      multifactorial, complex, and poorly known. Hallux valgus shows a predilection
      toward women. It is a progressive disorder with no treatment known to slow or
      stop progression. Surgery is indicated in healthy individuals when nonoperative
      measures fail. Adverse effects of surgery include infection and recurrence. Many
      procedures have been described, including soft tissue and bony reconstruction of
      the first ray. The procedure that is indicated depends on the severity of the
      deformity. 

PMID- 24559872
TI  - Metatarsalgia, lesser toe deformities, and associated disorders of the forefoot.
AB  - Forefoot pain in the adult often alters mobility and has a negative impact on
      quality of life. Metatarsalgia describes pain localized to the forefoot. Forefoot
      pain may be caused by conditions of the lesser toes themselves (eg, hammertoes,
      mallet toes, claw toes). The pathophysiology of lesser toe deformities is complex
      and is affected by the function of intrinsic and extrinsic muscle units. In
      addition to lesser toe and metatarsal abnormality, forefoot pain can be
      attributed to interdigital neuritis, disorders of the plantar skin, and
      gastrocsoleus contracture. Treatment of these conditions may include shoe
      modifications, appliances, therapeutic exercises, and surgical repair. 

PMID- 24559873
TI  - Arthritides of the foot.
AB  - Arthritis of the foot can be a difficult problem. It is initially managed with
      antiinflammatory medications and footwear modifications or bracing. However, a
      significant percentage of people with arthritis of the foot go on to require
      surgical intervention, which is most commonly arthrodesis. 

PMID- 24559874
TI  - Ankle arthritis: review of diagnosis and operative management.
AB  - The diagnostic and therapeutic options for ankle arthritis are reviewed. The
      current standard of care for nonoperative options include the use of nonsteroidal
      antiinflammatory drugs, corticosteroid injections, orthotics, and ankle braces.
      Other modalities lack high-quality research studies to delineate their
      appropriateness and effectiveness. The gold standard for operative intervention
      in end-stage degenerative arthritis remains arthrodesis, but evidence for the
      superiority in functional outcomes of total ankle arthroplasty is increasing. The
      next few years will enable more informed decisions and, with more prospective
      high-quality studies, the most appropriate patient population for total ankle
      arthroplasty can be identified. 

PMID- 24559875
TI  - Office-based management of adult-acquired flatfoot deformity.
AB  - Adult-acquired flatfoot deformity is associated with dysfunction of the posterior
      tibial tendon, leading to loss of the medial arch. Patients tend to present with
      medial pain and swelling, but later in the disease process can also present with
      lateral-sided pain. The mainstay of nonoperative treatment is nonsteroidal anti
      inflammatory drugs, weight loss, and orthotic insoles or brace use. The goals of
      therapy are to provide relief of symptoms and prevent progression of the
      deformity. If nonoperative management fails, a variety of surgical procedures are
      available; however, these require a lengthy recovery, and therefore patients
      should be advised accordingly. 

PMID- 24559877
TI  - Ankle sprains and instability.
AB  - Ankle injuries are among the most common injuries presenting to primary care
      providers and emergency departments and may cause considerable time lost to
      injury and long-term disability. Inversion injuries about the ankle involve about
      25% of all injuries of the musculoskeletal system and 50% of all sports-related
      injuries. Medial-sided ankle sprains occur less frequently than those on the
      lateral side. High ankle sprains occur less frequently in the general population,
      but do occur commonly in collision sports. Providers should apply the Ottawa
      ankle rules when radiography is indicated and refer fractures and more severe
      injuries to orthopedic surgery as needed. 

PMID- 24559876
TI  - The cavus foot.
AB  - The cavus, or high-arched, foot can present in either childhood or adulthood as a
      function of muscle imbalance. Neurologic, traumatic, and idiopathic processes
      have been identified, along with residual clubfoot, as the primary causes of
      adult cavus foot deformity. A thorough history and physical examination is
      important and can help identify the underlying cause of deformity. Conservative
      treatment modalities are always used first, with surgical intervention reserved
      for refractory cases. The goal of surgery is to correct muscle imbalance, which
      can be achieved via tendon transfers, corrective osteotomies, and, in the most
      severe cases, fusion. 

PMID- 24559878
TI  - Achilles tendon disorders.
AB  - Achilles tendon disorders include tendinosis, paratenonitis, insertional
      tendinitis, retrocalcaneal bursitis, and frank rupture. Patients present with
      pain and swelling in the posterior aspect of the ankle. Magnetic resonance
      imaging and ultrasound are helpful in confirming the diagnosis and guiding
      treatment. Nonsurgical management of Achilles tendon disorders includes
      nonsteroidal anti-inflammatory drugs, physical therapy, bracing, and footwear
      modification. Surgical treatment includes debridement of the diseased area of the
      tendon with direct repair. Tendon transfer may be necessary to augment the
      strength of the Achilles tendon. 

PMID- 24559879
TI  - Plantar heel pain.
AB  - Plantar heel pain is a common complaint encountered by orthopedic surgeons,
      internists, and family practitioners. Although it is most often caused by plantar
      fasciitis, this is a diagnosis of exclusion. Other mechanical, rheumatologic, and
      neurologic causes must be considered first. The history and physical examination
      are typically all that is needed to make the proper diagnosis, but diagnostic
      adjuncts are available to assist the clinician. When plantar fasciitis is
      diagnosed, conservative modalities must be tried first. Corticosteroid injections
      and extracorporeal shock-wave therapy may also be used. After 6 months of failed
      conservative treatments, surgical intervention should be considered.

PMID- 24559880
TI  - Outpatient assessment and management of the diabetic foot.
AB  - Patients with diabetes and peripheral neuropathy are at risk for foot deformities
      and mechanical imbalance of the lower extremity. Peripheral neuropathy leads to
      an insensate foot that puts the patient at risk for injury. When combined with
      deformity due to neuropathic arthropathy, or Charcot foot, the risks of impending
      ulceration, infection, and amputation are significant to the diabetic patient.
      Education of proper foot care and shoe wear cannot be overemphasized. For those
      with significant malalignment or deformity of the foot and ankle, referral should
      be made immediately to an orthopedic foot and ankle specialist. 

PMID- 24559881
TI  - Managing and treating common foot and ankle problems. Foreword.

PMID- 24559882
TI  - Managing and treating common foot and ankle problems. Preface.

PMID- 24559883
TI  - Reduced blood loss with ligation of medial circumflex pedicle during total hip
      arthroplasty with minimally invasive posterior approach.
AB  - A total hip arthroplasty procedure can lead to significant perioperative blood
      loss due to bleeding from the medial circumflex pedicle. When either the anterior
      or posterior approach is used, haemostasis of this pedicle, which is typically
      performed with electrocautery without dissection, can be inadequate. The purpose
      of this study was to evaluate the efficacy of a novel surgical technique in which
      the pedicleis is directly ligated. A single-centre, single-surgeon prospective
      study was performed to compare pedicle ligation to electrocautery (control
      group). In the ligation group, the pedicle was identified in front of the upper
      third of the quadratus femoris and ligated. The mean postoperative blood loss in
      the ligation group (293.4+/-34.8 mL) was significantly less than in the control
      group (419.0+/-36.8 mL) (P<0.05). Pedicle ligation is a simple procedure that
      reduces blood loss during total hip arthroplasty.

PMID- 24559884
TI  - Horizontal gaze palsy with progressive scoliosis in a Moroccan family.
AB  - Horizontal gaze palsy with progressive scoliosis (HGPPS) is a rare clinical
      condition characterized by a combination of horizontal gaze palsy, pendular
      nystagmus and scoliosis. Only a few cases have been previously described in the
      literature. Our observations serve to document the first cases in Morocco. 

PMID- 24559885
TI  - Impact of orthographic transparency on typical and atypical reading development:
      evidence in French-Spanish bilingual children.
AB  - The present study aimed to quantify cross-linguistic modulations of the
      contribution of phonemic awareness skills and visual attention span (VA Span)
      skills (number of visual elements that can be processed simultaneously) to
      reading speed and accuracy in 18 Spanish-French balanced bilingual children with
      and without developmental dyslexia. The children were administered two similar
      reading batteries in French and Spanish. The deficits of the dyslexic children in
      reading accuracy were mainly visible in their opaque orthography (French) whereas
      difficulties indexed by reading speed were observed in both their opaque and
      transparent orthographies. Dyslexic children did not exhibit any phonemic
      awareness problems in French or in Spanish, but showed poor VA Span skills
      compared to their control peers. VA span skills correlated with reading accuracy
      and speed measures in both Spanish and French, whereas phonemic awareness
      correlated with reading accuracy only. Overall, the present results show that the
      VA Span is tightly related to reading speed regardless of orthographic
      transparency, and that it accounts for differences in reading performance between
      good and poor readers across languages. The present findings further suggest that
      VA Span skills may play a particularly important role in building-up specific
      word knowledge which is critical for lexical reading strategies. 

PMID- 24559886
TI  - Matrix biology highlights.

PMID- 24559889
TI  - [Placenta accreta: can prenatal diagnosis be performed? Ultrasound and MRI
      interests. About 27 cases].
AB  - OBJECTIVES: To list ultrasonography signs identified when a placenta accreta is
      suspected. Secondary objectives are to analyze the relevance of diagnosis with
      ultrasonography and magnetic resonance imaging, and to know diagnosis
      circumstances in order to identify main risk factors. PATIENTS AND METHODS: We
      present a monocentric retrospective study. All the cases of placentas accreta,
      observed from 2005 to 2010 at Lille University Hospital (France), have been
      included. RESULTS: Twenty-seven patients had a placenta accreta during this
      period. There was an antenatal suspicion for 22 cases and 21 were confirmed after
      delivery. Six cases were discovered per-partum. Diagnosis was suspected after
      metrorrhagia for 41% of women. In case of antenatal diagnosis, 100% of the
      patients had an anterior placenta praevia and an uterine scare. Fifty percent of
      the placentas accreta diagnosed per-partum were posterior. The most frequently
      ultrasonography signs are "intra-placental lacuna" (85.7%), "abnormal
      vascularization" (71.4%), "loss of normal hypoechoic retroplacental myometrial
      zone" (66.7%), "irregularity of the vesical wall" (66.7%). Sensibility of
      ultrasonography screening is 78%. Twenty-one magnetic resonance imaging
      examinations executed secondarily confirmed the diagnosis in 66.7% of the cases.
      DISCUSSION AND CONCLUSION: Ultrasonography is a relevant exam for the diagnosis
      of placenta accreta. Posterior placenta should not be forsaken. Anterior placenta
      praevia in multiparous patients with a uterine scare should be a warning.

PMID- 24559890
TI  - [Hysteroscopic septoplasty: after miscarriages?].
AB  - OBJECTIVE: To assess reproductive outcome of women affected by septate uterus
      after surgical correction. PATIENTS AND METHODS: It is a retrospective study. The
      setting is a French university hospital. Surgery was performed on 66 patients
      between 2000 and 2010. Hysteroscopic metroplasty was performed in every group
      once the diagnosis was made. There were two groups: 35 patients affected by
      septate uterus had past history of miscarriages, preterm and term deliveries.
      Thirty-six patients had never been pregnant. RESULTS: In the group of 35 patients
      with a previous obstetric history, the rate of miscarriages was 57.1% before
      surgery and 10% after surgery. There was a significant gain of live birth ratio
      of 55% among women being pregnant after surgery compared to women being pregnant
      before surgery. For patients with no pregnancy before surgery, obstetrical
      results are the following ones: miscarriages 25.9%, preterm deliveries 11% and
      term deliveries 59.3%. DISCUSSION AND CONCLUSION: Hysteroscopic septoplasty is an
      easy technique with few complications in our study. Hysteroscopic septoplasty is
      strongly recommended after recurrent miscarriages or premature deliveries. We use
      to propose surgery to every patient affected by septate uterus, even if they have
      never been pregnant.

PMID- 24559893
TI  - Competent, proficient, advanced practice/expert--where are you in your career
      development?

PMID- 24559894
TI  - Nutrition and the kidney donor.

PMID- 24559892
TI  - Selected nutrition practices of women on hemodialysis and peritoneal dialysis:
      observations from the NKF-CRN Second National Research Question Collaborative
      Study.
AB  - OBJECTIVE: The objective of this study was to report selected nutrition behavior
      practices (type and amount of fat, fiber, and beverage intake) collected by self
      administered validated food frequency questionnaires (FFQs) as part of the 1998
      to 1999 NKF-CRN Second National Research Question Collaborative Study Group.
      DESIGN AND METHODS: This study was conducted on a prospective randomized cohort
      of 264 adult women 18 years of age or older that were on hemodialysis (HD) or
      peritoneal dialysis for more than 3 months and were receiving treatment in 116
      U.S. dialysis centers. These women completed the same self-administered validated
      FFQ used in the Women's Health Initiative Dietary Modification Trial. MAIN
      OUTCOME MEASURES: Main outcome measures included tabulated FFQ data and selected
      nutrition practices using descriptive statistics (frequency, percentage).
      Associations with selected demographic and geographic region variables were
      examined, and nutrition practice differences by age, registered dietitian full
      time equivalents, years on dialysis, and body mass index (BMI) categories were
      investigated using analyses of variance. RESULTS: Demographics (mean +/- standard
      deviation) were age (56.1 +/- 15.3 years), years on dialysis (5.3 +/- 4.6 years),
      and race/ethnicity (62% White, 30% Black) with 86% on HD. The nutrition behavior
      of taking the skin off of chicken was more prevalent in White women (P < .0005)
      whereas adding fat to cooking was higher in Black women (P < .0005). Differences
      in other selected nutrition practices were also observed. CONCLUSIONS: Low-fat
      intake behaviors were reported in 30% to 50% of the sample; fiber intake was
      minimal (mean 10 g/day). Self-administered FFQs may have limitations in
      calculating actual intake, but this is the first report of dietary patterns
      specifically in women undergoing maintenance dialysis from 1998 to 1999. These
      data could be used to increase fruit and vegetable intake within renal diet
      parameters and support awareness of healthier food choices.

PMID- 24559895
TI  - Benefits of using vaccines out of the cold chain: delivering meningitis A vaccine
      in a controlled temperature chain during the mass immunization campaign in Benin.
AB  - BACKGROUND: In October 2012, the Meningococcal A conjugate vaccine MenAfriVac was
      granted a label variation to allow for its use in a controlled temperature chain
      (CTC), at temperatures of up to 40 degrees C for not more than four days. This
      paper describes the first field use of MenAfriVac in a CTC during a campaign in
      Benin, December 2012, and assesses the feasibility and acceptability of the
      practice. METHODS: We implemented CTC in one selected district, Banikoara (target
      population of 147,207; 1-29 years of age), across 14 health facilities and 150
      villages. We monitored the CTC practice using temperature indicators and daily
      monitoring sheets. At the end of the campaign we conducted a face-to-face survey
      to assess vaccinators' and supervisors' experience with CTC. FINDINGS: A mix of
      strategies were implemented in the field to maximize the benefits from CTC
      practice, depending on the distance from health centre to populations and the
      availability of a functioning refrigerator in the health centre. Coverage across
      Banikoara was 105.7%. Over the course of the campaign only nine out of approx.
      15,000 vials were discarded due to surpassing the 4 day CTC limit and no vial was
      discarded because of exposure to a temperature higher than 40 degrees C or due to
      the Vaccine Vial Monitor (VVM) reaching its endpoint. Overall confidence and
      perceived usefulness of the CTC approach were very high among vaccinators and
      supervisors. INTERPRETATION: Vaccinators and supervisors see clear benefits from
      the CTC approach in low income settings, especially in hard-to-reach areas or
      where cold chain is weak. Taking advantage of the flexibility offered by CTC
      opens the door for the implementation of new immunization strategies to ensure
      all those at risk are protected.

PMID- 24559896
TI  - The effect of postnatal age on the early tactile manual abilities of preterm
      infants.
AB  - BACKGROUND: Although preterm infants possess early tactile manual abilities, the
      influence of the postnatal experience has not yet been systematically examined.
      AIMS: To investigate whether early tactile manual habituation, discrimination and
      recognition (following interference) of shape in preterm infants are modified by
      postnatal age. STUDY DESIGN: Prospective study. SUBJECTS: Forty preterm infants
      were assessed from the post-conceptional age (PCA) of 34 weeks. Two groups were
      made up according to postnatal age (PNA): low PNA (PNA<=10 days of life) and high
      PNA (PNA>=12 days of life). OUTCOME MEASURES: An object (prism or cylinder) was
      presented repeatedly in the left hand, and holding times of the object were
      recorded during each trial. RESULTS: Holding time was shorter for all preterm
      infants following successive presentation of the same object irrespective of
      postnatal age range. In the discrimination phase, the mean holding time for the
      novel object was longer than holding times in the last two habituation trials, in
      both PNA groups. Finally, the mean holding time of the familiar object presented
      in the recognition phase was shorter than the holding time of the novel object
      presented previously, but only in the low PNA group. CONCLUSIONS: Tactile manual
      habituation and discrimination of shape information is present in preterm infants
      at a post-conceptional age of 34 weeks, independently of postnatal age. However,
      tactile manual recognition of familiar shapes following interference is affected
      by length of postnatal experience. The significance of this last result is
      discussed in detail.

PMID- 24559897
TI  - Vascular training in Scotland and Northern Ireland: The trainee perspective prior
      to introduction of the new vascular curriculum.
AB  - BACKGROUND: The last decade has seen the evolution of vascular surgery from a sub
      specialty of general surgery to that of an independent, stand-alone specialty.
      The introduction of a vascular-only curriculum is anticipated to require
      significant change from the current provision for vascular surgical training to
      allow vascular trainees to acquire the specialist skills in elective, emergency,
      and endovascular surgery to provide endovascular services in the future. AIM: To
      provide an insight into current vascular training in Scotland and Northern
      Ireland. METHOD: Specialty trainees in general surgery, with a sub-specialty
      interest in vascular in Scotland and Northern Ireland were asked to carry out a
      voluntary online survey between May 2012 and July 2012. RESULTS: 22 specialty
      trainees/specialist registrars who have declared a sub-specialty interest in
      vascular surgery were identified and polled. 20 trainees completed the survey. 13
      trainees still participated in general surgical on-call rotas. Formal teaching
      opportunities were readily available but only 10 trainees could attend regularly.
      All trainees worked in units offering endovascular treatment for aneurysm and
      occlusive disease, but few had dedicated training sessions in endovascular
      skills. All endovascular simulation-based training was industry sponsored. The
      majority of trainees report a good overall training experience and are keen to
      see the implementation of a vascular-specific curriculum. 15 trainees had
      undertaken a dedicated period of research towards a higher degree, with only 50%
      based on a vascular topic. CONCLUSION: The majority of trainees reported a
      positive training experience with Scotland and Northern Ireland having great
      potential as vascular training deaneries. The survey identifies specific areas
      that could be improved by the development of the new curriculum in vascular
      surgery to provide excellent vascular training in Scotland and Northern Ireland.

PMID- 24559898
TI  - Penile cancer--Guideline adherence produces optimum results.
AB  - OBJECTIVE: To audit the management and outcome of penile cancer in a tertiary
      university teaching hospital, comparing our results to international best
      practice and published guidelines. METHODS: The Hospital Inpatient Enquiry
      database of the Mercy University Hospital was interrogated for penile cancer
      patients treated between 2001 and 2012. Data relating to presentation, local
      treatment, histology, lymph-node management, outcome and survival was recorded.
      Data were analysed using the Log Rank test, with significance defined as P <=
      0.05. RESULTS: Twenty-five patients were identified with a median age of 61
      years. The majority of cases at presentation were >= T2 (54%) and intermediate to
      high grade (76%). The median follow-up of patients was 3.75 years (range 9 months
      10 years). Overall survival was 76% (n = 19), these patients are all disease free
      to date. Disease-specific survival was 85% at 10 years. Penile cancer related
      mortality was 8% (n = 2), 4 patients (16%) died of non-penile cancer related
      causes. Twenty-two patients (88%) had surgery and 3 patients (12%) had
      radiotherapy. Based on EAU guidelines inguinal lymph node dissection (ILND) was
      performed in 64% (n = 16) of cases with 44% (n = 7) of these patients requiring
      concurrent bilateral pelvic lymph node dissection. Fifty percent (n = 8) of ILNDs
      showed metastatic disease. Ten year disease-specific survival for node negative
      versus node positive disease is 100% versus 57%. Thirty-two percent (n = 8) of
      patients received chemotherapy. CONCLUSIONS: Penile cancer is a rare oncological
      condition that often requires bilateral inguinal +/- pelvic lymph node dissection
      and should be managed according to published guidelines, in specialist centres in
      order to maximize outcomes.

PMID- 24559899
TI  - Enterocin HZ produced by a wild Enterococcus faecium strain isolated from a
      traditional, starter-free pickled cheese.
AB  - Bacteriogenic Enterococcus faecium HZ was identified by using biochemical (Strep
      API 20, API-50 CHL, fatty acid profile) and 16S rRNA analysis (99.99 %). Ent.
      faecium HZ was sensitive to clinically important antibiotics such as vancomycin,
      and did not have gelatinase and haemolysis activities. Enterocin HZ, a
      bacteriocin from Ent. faecium HZ, was sensitive to papain and tyripsin, but
      resistant to pepsin, lipase, catalase, alpha-amylase, organic solvents,
      detergents, beta-mercaptoethanol, and heat treatment (90  degrees C/30 min). It
      was biologically active at pH 2.0-9.0 and synthesised at the highest level in MRS
      or M17 broth at 32 or 37  degrees C with an inoculum amount of 0.1-0.5 % and an
      initial pH of 6.0-7.0. Enterocin HZ production reached maximum level at middle
      and late logarithmic phase and its molecular weight was ~4.5 kDa. It was active
      against some Gram-positive foodborne bacteria. Ent. faecium HZ or its bacteriocin
      enterocin HZ is a good candidate to be studied as a food biopreservative since
      enterocin HZ showed strong bactericidal activity against Listeria monocytogenes
      in UHT milk and also Ent. faecium HZ grew very well in milk and produced
      enterocin HZ at maximum level. 

PMID- 24559900
TI  - Words of wisdom. Re: Gonadal steroids and body composition, strength, and sexual
      function in men.

PMID- 24559901
TI  - Words of wisdom. Re: In older men an optimal plasma testosterone is associated
      with reduced all-cause mortality and higher dihydrotestosterone with reduced
      ischemic heart disease mortality, while estradiol levels do not predict
      mortality.

PMID- 24559902
TI  - Words of wisdom. Re: Penis size interacts with body shape and height to influence
      male attractiveness.

PMID- 24559903
TI  - Words of wisdom. Re: Intratumor heterogeneity and branched evolution revealed by
      multiregion sequencing.

PMID- 24559904
TI  - Words of wisdom. Re: Volume outcomes of cystectomy--is it the surgeon or the
      setting?

PMID- 24559905
TI  - Words of wisdom. Re: Final results of an EORTC-GU cancers group randomized study
      of maintenance bacillus Calmette-Guerin in intermediate- and high-risk Ta, T1
      papillary carcinoma of the urinary bladder: one-third dose versus full dose and 1
      year versus 3 years of maintenance.

PMID- 24559906
TI  - Accuracy of emergency physician-performed limited echocardiography for right
      ventricular strain.
AB  - BACKGROUND: Pulmonary embolism (PE) is a common emergency department (ED)
      diagnosis with a wide range in mortality rates. Methods to identify and risk
      stratify PE, including measuring right ventricular strain (RVS) by
      echocardiography (echo), are essential in providing effective and efficient care.
      A limited echo examination aims to expedite and increase availability of RVS
      determination through assessment at the bedside by the ED provider. OBJECTIVE:
      The objective is to determine the level of agreement and test characteristics of
      right ventricular dilation (RVd), as a marker of RVS, on limited echo compared
      with consultative echo. METHODS: This is a retrospective cohort study of
      consecutive ED patients undergoing limited echo examinations for chest pain,
      dyspnea, or hypotension and a subsequent consultative echo within 72 hours. kappa
      values and test characteristics were calculated to determine the level of
      agreement and accuracy between the limited echo examination and consultative echo
      for RVd and RVS. RESULTS: There were 411 focused examinations performed by 69
      different providers over a 12-month period (median, 5 examinations per provider).
      The prevalence of RVS on limited echo examination was 6.2% (n = 25). The kappa
      value for the level of agreement between limited and consultative echo for RVd
      was 0.44 (95% confidence intervals [CI], 0.27-0.61). The specificity of RVd on
      limited echo for RVS was 0.98 (95% CI, 0.96-0.99) with 6 false-positive
      categorizations, whereas the sensitivity was 0.26 (95% CI, 0.16-0.37).
      CONCLUSIONS: In this retrospective cohort study, limited echo demonstrated
      moderate agreement with consultative echo for RVd. Right ventricular dilation on
      limited echo was highly specific for RVS but had low sensitivity.

PMID- 24559908
TI  - Comparing performance of video and direct laryngoscopes for intubation during
      prehospital cardiopulmonary resuscitation.

PMID- 24559907
TI  - Thirty and ninety days mortality predictive value of admission and in-hospital
      procalcitonin and mid-regional pro-adrenomedullin testing in patients with
      dyspnea. Results from the VERyfing DYspnea trial.
AB  - INTRODUCTION: Mid-regional pro-atrial natriuretic peptide (MR-proANP),
      procalcitonin (PCT), and mid-regional pro-adrenomedullin (MR-proADM) demonstrated
      usefulness for management of emergency department patients with dyspnea. METHODS:
      To evaluate in patients with dyspnea, the prognostic value for 30 and 90 days
      mortality and readmission of PCT, MR-proADM, and MR-proANP, a multicenter
      prospective study was performed evaluating biomarkers at admission, 24 and 72
      hours after admission. Based on final diagnosis, patients were divided into acute
      heart failure (AHF), primary lung diseases, or both (AHF + NO AHF). RESULTS: Five
      hundred one patients were enrolled. Procalcitonin and MR-proADM values at
      admission and at 72 hours were significantly (P < .001) predictive for 30-day
      mortality: baseline PCT with an area under the curve (AUC) of 0.70 and PCT at 72
      hours with an AUC of 0.61; baseline MR-proADM with an AUC of 0.62 and MR-proADM
      at 72 hours with an AUC of 0.68. As for 90-day mortality, both PCT and MR-proADM
      baseline and 72 hours values showed a significant (P < .0001) predictive ability:
      baseline PCT with an AUC of 0.73 and 72 hours PCT with an AUC of 0.64; baseline
      MR-proADM with an AUC of 0.66 and 72 hours MR-proADM with an AUC of 0.71. In AHF,
      group biomarkers predicted rehospitalization and mortality at 90 days, whereas in
      AHF + NO AHF group, they predict mortality at 30 and 90 days. CONCLUSIONS: In
      patients admitted for dyspnea, assessment of PCT plus MR-proADM improves risk
      stratification and management. Combined use of biomarkers is able to predict in
      the total cohort both rehospitalization and death at 30 and 90 days.

PMID- 24559910
TI  - Differential antibiosis against Helicoverpa armigera exerted by distinct
      inhibitory repeat domains of Capsicum annuum proteinase inhibitors.
AB  - Plant defensive serine proteinase inhibitors (PIs) are known to have negative
      impact on digestive physiology of herbivore insects and thus have a crucial role
      in plant protection. Here, we have assessed the efficacy and specificity of three
      previously characterized inhibitory repeat domain (IRD) variants from Capsicum
      annuum PIs viz., IRD-7, -9 and -12 against gut proteinases from Helicoverpa
      armigera. Comparative study of in silico binding energy revealed that IRD-9
      possesses higher affinity towards H. armigera serine proteinases as compared to
      IRD-7 and -12. H. armigera fed on artificial diet containing 5 TIU/g of
      recombinant IRD proteins exhibited differential effects on larval growth,
      survival rate and other nutritional parameters. Major digestive gut trypsin and
      chymotrypsin genes were down regulated in the IRD fed larvae, while few of them
      were up-regulated, this indicate alterations in insect digestive physiology. The
      results corroborated with proteinase activity assays and zymography. These
      findings suggest that the sequence variations among PIs reflect in their efficacy
      against proteinases in vitro and in vivo, which also could be used for developing
      tailor-made multi-domain inhibitor gene(s).

PMID- 24559909
TI  - Cost-effectiveness of a nurse facilitated, cognitive behavioural self-management
      programme compared with usual care using a CBT manual alone for patients with
      heart failure: secondary analysis of data from the SEMAPHFOR trial.
AB  - OBJECTIVE: To assess the cost-effectiveness of a nurse facilitated, cognitive
      behavioural self-management programme for patients with heart failure compared
      with usual care including the un-facilitated access to the same manual, from the
      perspective of the NHS. DESIGN: Data were obtained from a pragmatic, multi
      centre, randomized controlled 'open' trial conducted in seven centres in the UK
      between 2006 and 2008. Effectiveness was estimated as Quality-Adjusted Life
      Years. Resource use was measured prospectively on all patients using information
      provided by patients in postal questionnaires, case-note review, electronic
      record review and interviews with patients. Unit costs were obtained from the
      literature and applied to the relevant resource use to estimate total costs.
      Multiple imputation was used to handle missing data. RESULTS: There were no
      substantial differences in the utility scores between treatment groups in all
      follow-up assessments, in the use of medication or outpatient visits and both
      groups report a similar frequency of contact with health care professionals.
      After controlling for baseline utility and using imputed dataset, treatment was
      associated with a reduction in QALY of 0.004 and a additional cost of L69.49. The
      probability that the intervention is cost-effective for thresholds between
      L20,000 and L30,000 is around 45%. CONCLUSIONS: There is little evidence that the
      addition of the intervention had any effect on costs or outcomes. The uncertainty
      around both estimates of cost and effectiveness mean that it is not reasonable to
      make recommendations based on cost-effectiveness alone.

PMID- 24559911
TI  - Neolignans as xanthine oxidase inhibitors from Hyptis rhomboides.
AB  - The active fraction from the EtOH extract of Hyptis rhomboides against xanthine
      oxidase was identified by use of an HPLC microfractionation-centrifugal vacuum
      evaporation-bioassay hyphenated technique. Scale-up separation of the active
      subfractions using semi-preparative RP-HPLC provided 13 phenylpropanoid
      compounds, including O-styrenylneolignans, hyprhombins A-C, epihyprhombin B, and
      hyprhombin B methyl ester, and O-caffeoylnorneolignans, hyprhombins D and E. All
      of these compounds shared a common 1,4-benzodioxane skeleton, as established by
      spectroscopic analyses. Hyprhombin C and epihyprhombin B exhibited better anti
      xanthine oxidase activity than allopurinol, with IC50 values of 0.6 and 2.0 MUM,
      respectively.

PMID- 24559912
TI  - Metabolic regulation of insulin secretion.
AB  - Regulation of metabolic fuel homeostasis is a critical function of beta-cells,
      which are located in the islets of Langerhans of the animal pancreas. Impairment
      of this beta-cell function is a hallmark of pancreatic beta-cell failure and may
      lead to development of type 2 diabetes mellitus. beta-Cells are essentially "fuel
      sensors" that monitor and react to elevated nutrient load by releasing insulin.
      This response involves metabolic activation and generation of metabolic coupling
      factors (MCFs) that relay the nutrient signal throughout the cell and induce
      insulin biosynthesis and secretion. Glucose is the most important insulin
      secretagogue as it is the primary fuel source in food. Glucose metabolism is
      central to generation of MCFs that lead to insulin release, most notably ATP. In
      addition, other classes of nutrients are able to augment insulin secretion and
      these include members of the lipid and amino acid family of nutrients. Therefore,
      it is important to investigate the interplay between glucose, lipid, and amino
      acid metabolism, as it is this mixed nutrient sensing that generate the MCFs
      required for insulin exocytosis. The mechanisms by which these nutrients are
      metabolized to generate MCFs, and how they impact on beta-cell insulin release
      and function, are discussed in detail in this article. 

PMID- 24559913
TI  - Proinsulin entry and transit through the endoplasmic reticulum in pancreatic beta
      cells.
AB  - Insulin is an essential hormone for maintaining metabolic homeostasis in the
      body. To make fully bioactive insulin, pancreatic beta cells initiate synthesis
      of the insulin precursor, preproinsulin, at the cytosolic side of the endoplasmic
      reticulum (ER), whereupon it undergoes co- and post-translational translocation
      across the ER membrane. Preproinsulin is cleaved by signal peptidase to form
      proinsulin that folds on the luminal side of the ER, forming three evolutionarily
      conserved disulfide bonds. Properly folded proinsulin forms dimers and exits from
      the ER, trafficking through Golgi complex into immature secretory granules
      wherein C-peptide is endoproteolytically excised, allowing fully bioactive two
      chain insulin to ultimately be stored in mature granules for insulin secretion.
      Although insulin biosynthesis has been intensely studied in recent decades, the
      earliest events, including proinsulin entry and exit from the ER, have been
      relatively understudied. However, over the past 5 years, more than 20 new insulin
      gene mutations have been reported to cause a new syndrome termed Mutant INS-gene
      induced Diabetes of Youth (MIDY). Although these mutants have not been completely
      characterized, most of them affect proinsulin entry and exit from the ER. Here,
      we summarize our current knowledge about the early events of insulin biosynthesis
      and review recent advances in understanding how defects in these events may lead
      to pancreatic beta cell failure. 

PMID- 24559914
TI  - Metabolism-secretion coupling and mitochondrial calcium activities in clonal
      pancreatic beta-cells.
AB  - Pancreatic beta-cells are the only cells capable of lowering blood glucose by
      secreting insulin. The beta-cell continuously adjusts its secretory activity to
      substrate availability in order to keep blood glucose levels within the
      physiological range--a process called metabolism-secretion coupling. Glucose is
      readily taken up by the beta-cell and broken down into intermediates that fuel
      oxidative metabolism inside the mitochondria to generate ATP. The resulting
      increase in the ATP/ADP ratio causes closure of plasma membrane KATP channels,
      thereby depolarizing the cell and triggering the opening of voltage-gated Ca2+
      channels. Consequential oscillations of cytosolic Ca2+ not only mediate the
      exocytosis of insulin granules but are also relayed to other subcellular
      compartments including the mitochondria, where Ca2+ is required to accelerate
      mitochondrial metabolism in response to nutrient stimulation. The mitochondrial
      Ca2+ uptake machinery plays a fundamental role in this feed-forward mechanism
      that guarantees sustained insulin secretion and, thus, represents a promising
      therapeutic target for type 2 diabetes.

PMID- 24559915
TI  - Metabolic syndrome and ionic channels in pancreatic beta cells.
AB  - Worldwide increase in the prevalence of metabolic syndrome and diabetes mellitus
      type 2 (DM2) during the past decades has converted them into a global epidemic
      disease. It is not well understood how these metabolic disorders initiate, but an
      increase in food consumption associated to low physical activity leads to
      increase in body weight and obesity. This in turn, elevates circulating lipids
      and cytokines release by adipose tissue, give the organism a chronic inflammation
      and potentiate insulin secretion, causing insulin resistance. Depending on
      genetics and probably other environmental factors, after a long period of
      hyperactivity, pancreatic beta cells become exhausted and DM2 overcomes.
      Pancreatic beta cells are the only source of insulin known in mammals. They are
      unique because of their ability to sense and transform fuels into a chemical
      signal, which affects mainly all the cells in the organism. Many other factors
      affect insulin secretion. We will focus on the alterations of glucose-induced
      insulin secretion coupling, particularly in ionic channels that have crucial
      importance in this process. Different channel types can be affected by metabolic
      syndrome. The most studied are K(ATP) and other potassium channels, calcium,
      sodium, and TRP channels. Much information comes from rodents that do not express
      exactly the same proportion and type of channels than humans. However, getting
      insight of how do they participate in insulin secretion and how to modulate them
      is important to completely understand beta-cell physiology and pathophysiological
      reactions to metabolic syndrome and diabetes, in order to stop the epidemic of
      these metabolic disorders.

PMID- 24559916
TI  - The beta cell immunopeptidome.
AB  - Type 1 diabetes results from the autoimmune-mediated destruction of insulin
      secreting beta cells, leading to beta cell loss and insulin deficiency.
      Presentation of peptides derived from beta cell proteins to autoreactive
      lymphocytes is critical for the development of disease, and the list of antigens
      recognized is increasing. A number of these proteins are found within the beta
      cell secretory granules, which are transiently exposed to the immune system
      during normal cellular function. How the interplay of environmental and genetic
      determinants culminates in destructive autoimmunity remains to be clearly
      defined. Nonconventional presentation of peptide ligands, posttranslational
      modification of peptides, and the role of the gut microbiome in the development
      of the immune system are all considered central topics in disease pathogenesis.
      Each of these may provide a mechanism by which presentation of antigenic peptides
      in the target tissue differs from presentation in the thymus, allowing
      autoreactive cells to escape tolerance induction. The high metabolic demand on
      pancreatic islets, the high concentration of granule proteins, and the
      susceptibility of islets to cellular stress may all contribute to the
      presentation of abnormal ligands in the pancreas. Moreover, the finding that
      small molecules can alter the repertoire of peptides presented by major
      histocompatibility complex molecules provides a tantalizing hypothesis for the
      presentation of autoantigenic peptides in the presence of microbial or endogenous
      metabolites. In this chapter, we provide an overview of the immunopeptidome of
      beta cells and the key factors that may influence presentation of beta cell
      antigens to the immune system. 

PMID- 24559917
TI  - Autophagy and pancreatic beta-cells.
AB  - Autophagy plays a key role in maintaining pancreatic beta-cell homeostasis.
      Deregulation of this process is associated with loss of beta-cell mass and
      function, and it is likely to be involved in type 2 diabetes development and
      progression. Evidence that modulation of autophagy may be beneficial to preserve
      beta-cell mass and function is beginning to accumulate although the complexity of
      this process, the intricate link between autophagy and apoptosis, and the fine
      balance between the protective and the disruptive role of autophagy make it very
      difficult to develop interventional strategies. This chapter provides an overview
      of the role of constitutive and adaptive autophagy in pancreatic beta-cell and in
      the context of type 2 diabetes.

PMID- 24559918
TI  - The somatostatin receptor in human pancreatic beta-cells.
AB  - The peptide hormone somatostatin (SST) is produced in the brain, the gut, and in
      delta-cells in pancreatic islets of Langerhans. SST secretion from delta-cells is
      stimulated by glucose, amino acids, and glucagon-like peptide-1. Exogenous SST
      strongly inhibits the secretion of the blood glucose-regulating hormones insulin
      and glucagon from pancreatic beta-cells and alpha-cells, respectively. Endogenous
      SST secreted from delta-cells is a paracrine regulator of insulin and glucagon
      secretion, although the exact physiological significance of this regulation is
      unclear. Secreted SST binds to specific receptors (SSTRs), which are coupled to
      Gi/o proteins. In both beta- and alpha-cells, activation of SSTRs suppresses
      hormone secretion by reducing cAMP levels, inhibiting electrical activity,
      decreasing Ca2+ influx through voltage-gated Ca2+ channels and directly reducing
      exocytosis in a Ca2+ and cAMP-independent manner. In rodents, beta-cells express
      predominantly SSTR5, whereas alpha-cells express SSTR2. In human islets, SSTR2 is
      the dominant receptor in both beta- and alpha-cells, but other isoforms also
      contribute to the SST effects. Evidence from rodent models suggests that SST
      secretion from delta-cells is dysregulated in diabetes mellitus, which may
      contribute to the metabolic disturbances in this disease. SST analogues are
      currently used for the treatment of hyperinsulinism and other endocrine
      disorders, including acromegaly and Cushing's syndrome.

PMID- 24559919
TI  - Modulation of the pancreatic islet-stress axis as a novel potential therapeutic
      target in diabetes mellitus.
AB  - Loss of pancreatic islet function and insulin-producing beta cell mass is a
      central hallmark in the pathogenesis of both type 1 and type 2 diabetes. While in
      type 1 diabetes this phenomenon is due to an extensive destruction of beta cells
      caused by an autoimmune process, the mechanisms resulting in beta cell failure in
      type 2 diabetes are different and less clear. Also, beta cell destruction in type
      1 diabetes occurs early and is the initial step in the pathogenetic process,
      while beta cell loss in type 2 diabetes after an initial phase of
      hyperinsulinemia due to the underlying insulin resistance occurs relatively late
      and it is less pronounced. Since diabetes mellitus is the most frequent endocrine
      disease, with an increasing high prevalence worldwide, huge efforts have been
      made over the past many decades to identify predisposing genetic, environmental,
      and nutritional factors in order to develop effective strategies to prevent the
      disease. In parallel, extensive studies in different cell systems and animal
      models have helped to elucidate our understanding of the physiologic function of
      islets and to gain insight into the immunological and non-immunological
      mechanisms of beta cell destruction and failure. Furthermore, currently emerging
      concepts of beta cell regeneration (e.g., the restoration of the beta cell pool
      by regenerative, proliferative and antiapoptotic processes, and recovery of
      physiologic islet function) apparently is yielding the first promising results.
      Recent insights into the complex endocrine and paracrine mechanisms regulating
      the physiologic function of pancreatic islets, as well as beta cell life and
      death, constitute an essential part of this new and exciting area of diabetology.
      For example, understanding of the physiological role of glucagon-like peptide 1
      has resulted in the successful clinical implementation of incretin-based
      therapies over the last years. Further, recent data suggesting paracrine effects
      of growth hormone-releasing hormone and corticotropin-releasing hormone on the
      regulation of pancreatic islet function, survival, and proliferation as well as
      on local glucocorticoid metabolism provide evidence for a potential role of the
      pancreatic islet-stress axis in the pathophysiology of diabetes mellitus. In this
      chapter, we provide a comprehensive overview of current preventive and
      regenerative concepts as a basis for the development of novel therapeutic
      approaches to the treatment of diabetes mellitus. A particular focus is given on
      the potential of the pancreatic islet-stress axis in the development of novel
      regenerative strategies. 

PMID- 24559920
TI  - Regenerative medicine for diabetes: differentiation of human pluripotent stem
      cells into functional beta-cells in vitro and their proposed journey to clinical
      translation.
AB  - Diabetes is a group of metabolic diseases, rising globally at an alarming rate.
      Type 1 (juvenile diabetes) is the autoimmune version of diabetes where the
      pancreas is unable to produce insulin, whereas type 2 (adult onset diabetes) is
      caused due to insulin resistance of the cells. In either of the cases, elevated
      blood glucose levels are observed which leads to progressive comorbidity like
      renal failure, cardiovascular disease, retinopathy, etc. Metformin, sulphonyl
      urea group of drugs, as well as insulin injections are the available therapies.
      In advanced cases of diabetes, the drug alone or drug in combination with insulin
      injections are not able to maintain a steady level of blood glucose. Moreover,
      frequent insulin injections are rather cumbersome for the patient. So,
      regenerative medicine could be a permanent solution for fighting diabetes. Islet
      transplantation has been tried with a limited amount of success on a large
      population of diabetics because of the shortage of cadaveric pancreas. Therefore,
      the best proposed alternative is regenerative medicine involving human
      pluripotent stem cell (hPSC)-derived beta islet transplantation which can be
      obtained in large quantities. Efficient protocols for in vitro differentiation of
      hPSC into a large number of sustained insulin-producing beta cells for
      transplantation will be considered to be a giant leap to address global rise in
      diabetic cases. Although most of the protocols mimic in vivo pancreatic
      development in humans, considerable amount of lacuna persists for near-perfect
      differentiation strategies. Moreover, beta islets differentiated from hPSC have
      not yet been successfully translated under clinical scenario.

PMID- 24559921
TI  - The calcium-sensing receptor and beta-cell function.
AB  - In addition to its central role controlling systemic calcium homeostasis, the
      extracellular calcium-sensing receptor (CaSR) can be found on multiple cell types
      not associated with controlling plasma calcium. The endocrine pancreas is one
      such tissue, and it is apparent that the receptor plays an important role in
      regulating beta-cell function. During exocytosis, divalent cations are coreleased
      with insulin and their concentration within the restricted intercellular
      compartments of the pancreatic islet increases sufficiently to activate the CaSR
      on neighboring cells. Acute and chronic activation of the receptor has multiple
      effects on the beta-cell, from increasing cadherin-based cell-cell adhesion to
      directly altering the expression and function of various potassium and voltage
      dependent calcium channels. The promiscuous activation of multiple binding
      partners improves cell adhesion, cell coupling, and cell-to-cell communication
      within the islet and is the basis for the effect of the CaSR on beta-cell
      function and improved glucose responsiveness. 

PMID- 24559922
TI  - Cellular inhibitor of apoptosis protein-1 and survival of beta cells undergoing
      endoplasmic reticulum stress.
AB  - Pancreatic beta cells rely heavily on the endoplasmic reticulum (ER) to process
      folding and posttranslational modification of a large amount of insulin and many
      other proteins and are therefore vulnerable to ER stress. The role of the ER is
      thus crucial in the regulation of beta cell function and survival through the
      unfolded protein response (UPR) pathways. However, the UPR can either allow cells
      to survive by adapting to stress or kill cells through apoptosis in a context
      dependent manner. How cell fate is determined following UPR activation remains
      enigmatic. In this review, we discuss the molecular mechanisms linking ER stress
      to beta cell survival or apoptosis. Specifically, we focus on the role of the
      cellular inhibitor of apoptosis protein-1 and propose a new model for
      understanding survival of beta cells undergoing ER stress. 

PMID- 24559923
TI  - beta-Cell responses to nitric oxide.
AB  - Autoimmune diabetes is characterized by the selective destruction of insulin
      secreting beta-cells that occurs during an inflammatory reaction in and around
      pancreatic islets of Langerhans. Cytokines such as interleukin-1, released by
      activated immune cells, have been shown to inhibit insulin secretion from
      pancreatic beta-cells and cause islet destruction. In response to cytokines, beta
      cells express inducible nitric oxide synthase and produce micromolar levels of
      the free radical nitric oxide. Nitric oxide inhibits the mitochondrial oxidation
      of glucose resulting in an impairment of insulin secretion. Nitric oxide is also
      responsible for cytokine-mediated DNA damage in beta-cells. While nitric oxide
      mediates the inhibitory and toxic effects of cytokines, it also activates
      protective pathways that allow beta-cells to recover from this damage. This
      review will focus on the dual role of nitric oxide as a mediator of cytokine
      induced damage and the activator of repair mechanisms that protect beta-cells
      from cytokine-mediated injury. 

PMID- 24559924
TI  - Activated protein C and its potential applications in prevention of islet beta
      cell damage and diabetes.
AB  - Activated protein C (APC) is derived from its precursor, protein C (PC).
      Originally thought to be synthesized exclusively by the liver, recent reports
      have shown that PC is also produced by many other cells including pancreatic
      islet beta cells. APC functions as a physiological anticoagulant with anti
      inflammatory, anti-apoptotic, and barrier-stabilizing properties. APC exerts its
      protective effects via an intriguing mechanism requiring combinations of
      endothelial PC receptor, protease-activated receptors, epidermal growth factor
      receptor, Tie2 or CD11b, depending on cell types. Diabetes is a chronic condition
      resulted from the body's inability to produce and/or properly use insulin. The
      prevalence of diabetes has risen dramatically and has become one of the major
      causes of premature mortality and morbidity worldwide. Diabetes prevention is an
      ideal approach to reduce this burden. Type 1 and type 2 diabetes are the major
      forms of diabetes mellitus, and both are characterized by an autoimmune response,
      intraislet inflammation, beta-cell apoptosis, and progressive beta-cell loss.
      Protecting beta-cell from damage is critical in both prevention and treatment of
      diabetes. Recent in vitro and animal studies show that APC's strong anti
      inflammatory and anti-apoptotic properties are beneficial in preventing beta-cell
      destruction and diabetes in the NOD mouse model of type 1 diabetes. Future
      preventive and therapeutic uses of APC in diabetes look very promising. 

PMID- 24559925
TI  - Zinc and its transporters, pancreatic beta-cells, and insulin metabolism.
AB  - Zinc is an essential trace metal for life. Two families of zinc transporters,
      SLC30A (ZNT) and SLC39A (ZIP) are required for maintaining cellular zinc
      homeostasis. ZNTs function to decrease cytoplasmic zinc concentrations whereas
      ZIPs do the opposite. Expression of zinc transporters can be tissue/cell-type
      specific or ubiquitous. Zinc transporters that are limited in tissue/cell
      distributions usually perform specialized tasks to satisfy biological processes
      in a given cell. For example, ZNT8 is mainly expressed in beta-cells and
      functions to deliver zinc into granules for insulin maturation and secretion.
      Many other zinc transporters are also expressed in beta-cells. Defects in these
      zinc transporters have been associated with abnormalities in insulin synthesis,
      maturation, and secretion and subsequent glucose metabolism. This review focuses
      on the specific roles of zinc and its transporters in insulin metabolism and
      describes the current knowledge of the function of zinc transporters in beta-cell
      health in animal knockout mouse models with respect to diabetes development in
      humans. 

PMID- 24559926
TI  - The NOTCH pathway in beta-cell growth and differentiation.
AB  - Beta-cell replacement represents the optimal therapy for type 1 diabetes. Efforts
      to manipulate beta-cell proliferation and differentiation could be advanced by a
      better understanding of the normal pathways regulating beta-cell development and
      renewal. NOTCH signaling is a highly conserved pathway which plays a central role
      in pancreas development. Cell-lineage tracing has revealed the reactivation of
      the NOTCH pathway in adult human beta cells cultured under conditions which
      induce cell proliferation and dedifferentiation. Inhibition of NOTCH signaling in
      dedifferentiated cells following ex vivo expansion has been shown to promote
      restoration of the beta-cell phenotype. This approach may increase the
      availability of functional beta cells for transplantation. 

PMID- 24559927
TI  - Roles of HNF1alpha and HNF4alpha in pancreatic beta-cells: lessons from a
      monogenic form of diabetes (MODY).
AB  - Mutations in the genes encoding hepatocyte nuclear factor (HNF)1alpha and
      HNF4alpha cause a monogenic form of diabetes mellitus known as maturity-onset
      diabetes of the young (MODY). The primary cause of MODY is an impairment of
      glucose-stimulated insulin secretion by pancreatic beta-cells, indicating the
      important roles of HNF1alpha and HNF4alpha in beta-cells. Large-scale genetic
      studies have clarified that the common variants of HNF1alpha and HNF4alpha genes
      are also associated with type 2 diabetes, suggesting that they are involved in
      the pathogenesis of both diseases. Recent experimental studies revealed that
      HNF1alpha controls both beta-cell function and growth by regulating target genes
      such as glucose transporter 2, pyruvate kinase, collectrin, hepatocyte growth
      factor activator, and HNF4alpha. In contrast, HNF4alpha mainly regulates the
      function of beta-cells. Although direct target genes of HNF4alpha in beta-cells
      are largely unknown, we recently identified Anks4b as a novel target of HNF4alpha
      that regulates beta-cell susceptibility to endoplasmic reticulum stress. Studies
      of MODY have led to a better understanding of the molecular mechanism of glucose
      stimulated insulin secretion by pancreatic beta-cells. 

PMID- 24559928
TI  - Role of the mammalian target of rapamycin (mTOR) complexes in pancreatic beta
      cell mass regulation.
AB  - Exquisite regulation of insulin secretion by pancreatic beta-cells is essential
      to maintain metabolic homeostasis. beta-Cell mass must be accordingly adapted to
      metabolic needs and can be largely modified under different situations. The
      mammalian target of rapamycin (mTOR) complexes has been consistently identified
      as key modulators of beta-cell mass. mTOR can be found into two different
      complexes, mTORC1 and mTORC2. Under systemic insulin resistance, mTORC1/mTORC2
      signaling in beta-cells is needed to increase beta-cell mass and insulin
      secretion. However, type 2 diabetes arises when these compensatory mechanisms
      fail, being the role of mTOR complexes still obscure in beta-cell failure. In
      this chapter, we introduce the protein composition and regulation of mTOR
      complexes and their role in pancreatic beta-cells. Furthermore, we describe their
      main signaling effectors through the review of numerous animal models, which
      indicate the essential role of mTORC1/mTORC2 in pancreatic beta-cell mass
      regulation. 

PMID- 24559929
TI  - The pancreatic beta cell. Preface.

PMID- 24559930
TI  - Hashimoto's encephalopathy mimicking presenile dementia.
AB  - Hashimoto's encephalopathy (HE), which carries kaleidoscopic clinical
      presentations, is easily misdiagnosed in clinical practice. Early diagnosis and
      prompt initiation of steroid therapy are associated with good prognosis. We
      describe a 50-year-old female patient who had subclinical hypothyroidism and who
      presented herself with gradual cognitive impairment, accompanied with auditory
      hallucination and delusion. Increased anti-thyroid antibodies titers were found
      in her serum and cerebrospinal fluid. The HE diagnosis was confirmed using the
      laboratory test for anti-thyroid antibodies along with the patient's clinical
      presentation. We treated her with steroid pulse therapy, and the results were
      favorable. We highlight this case to call for early diagnosis and prompt
      intervention of HE in clinical practice. 

PMID- 24559931
TI  - Screening and analysis of 940 organic micro-pollutants in river sediments in
      Vietnam using an automated identification and quantification database system for
      GC-MS.
AB  - In order to obtain a detailed picture of pollution by organic micro-pollutants in
      Vietnamese rivers, 940 semi-volatile organic compounds in river sediments
      collected from four major cities were examined by a comprehensive gas
      chromatography-mass spectrometry-database. The number of detected chemicals at
      each site ranged from 49 to 158 (median 96 out of 940) with 185 analytes detected
      at least once in the survey. The substances detected with high frequency (over
      80%) and high concentrations were n-alkanes, phthalates, sterols and PAHs. For
      most substances, sediments from metropolitan areas (Hanoi and Ho Chi Minh City)
      were more heavily contaminated than those in rural and suburban areas. Sterols
      were observed in nearly 100% of sediments at extremely high concentrations,
      suggesting that the studied rivers were contaminated by sewage. Pyrethroids
      (permethrin-1 and -2) were the most dominant insecticides found in inner canals
      of Hanoi and Ho Chi Minh City. Deltamethrin was only detected at a site in Hanoi
      at an elevated concentration. This reflects that pyrethroids are used for the
      protection of private and public health rather than for agriculture. p,p'-DDE and
      p,p'-DDD were the dominant members of the DDT family of chemicals detected,
      indicating no recent inputs of DDTs in the study areas. PCBs residues were lower
      than those in other Asian countries, which suggest historically much lower use of
      PCBs in Vietnam. PAHs pollution in urban areas is caused by the runoff of
      petroleum products and vehicle exhaust gases, whereas in rural and suburban
      areas, the combustion of fossil fuels and biomass is major sources of PAHs.
      Overall, the study confirmed that rivers in Vietnam were heavily polluted mainly
      by domestic wastewater. 

PMID- 24559932
TI  - Gold and silver nanoparticle effects on ammonia-oxidizing bacteria cultures under
      ammoxidation.
AB  - Owing to their wide application in industry and manufacturing, understanding the
      environmental safety of gold (Au) and silver (Ag) nanoparticles entering aquatic
      environment is a global issue of concern. For this study, ammonia-oxidizing
      bacteria (AOB) enrichment cultures reproduced from surface sediments taken from
      the Jiulong River estuary wetlands (Fujian Province, China) were spiked with nano
      Ag and nano-Au to determine their impact on ammoxidation and the mechanisms
      involved in the process. Results showed that nano-Ag significantly inhibited
      bacterial ammoxidation in aquatic environment, with the average ammoxidation rate
      decreasing with increasing nano-Ag concentration. The average ammoxidation rate
      was significantly correlated to the Shannon index, the Simpson index, and AOB
      abundance. This suggested that ammoxidation inhibition resulted primarily from
      AOB biodiversity and abundance reduction, caused by the antibacterial property of
      nano-Ag. However, AOB biodiversity and abundance as well as bacterial
      ammoxidation were not inhibited by nano-Au (with a maximum experimental
      concentration of 2 mg L(-1)). Moreover, an insignificant correlation was found
      between AOB biodiversity and abundance and the average ammoxidation rate under
      the nano-Au treatment. Given that ammoxidation is regarded as a rate-limiting
      procedure in nitrogen (N) circulation, nano-Ag would affect N cycling but nano-Au
      would not after entering aquatic environments. Identified nano-Ag and nano-Au
      impacts on ammonium nitrogen transformation could be generalized in aquatic
      environment according to their extensive representation in the phylogenetic tree.

PMID- 24559933
TI  - Use of tar pitch as a binding and reductant of BFD waste to produce reactive
      materials for environmental applications.
AB  - In this work, a new approach is presented for the modification of the hazardous
      steel industry waste BFD (Blast Furnace Dust) into a versatile material for
      application in environmental remediation processes. Tar pitch, another waste, was
      used to agglomerate the very fine (submicrometric) dust particles to produce a
      compact and robust pelletized material that under simple thermal treatment
      produces notably reactive reduced Fe phases. SEM, TG/DTA, Mossbauer, XRD, Raman,
      BET and elemental analyses indicated that the tar/BFD composite (1:1wt ratio)
      pellets treated at 400, 600 and 800 degrees C lead to tar decomposition to form a
      carbon binding coat concomitant with the reduction of the Fe oxides to produce
      primarily Fe3O4 (magnetite), FeO (wustite) and Fe(0). Preliminary reactivity
      studies indicated that these treated composites, especially at 800 degrees C, are
      active for the reduction of Cr(VI)aq and for the elimination of textile dye via
      reduction and the Fenton reaction. 

PMID- 24559934
TI  - Co-occurrence correlations of heavy metals in sediments revealed using network
      analysis.
AB  - In this study, the correlation-based study was used to identify the co-occurrence
      correlations among metals in marine sediment of Hong Kong, based on the long-term
      (from 1991 to 2011) temporal and spatial monitoring data. 14 stations out of the
      total 45 marine sediment monitoring stations were selected from three
      representative areas, including Deep Bay, Victoria Harbour and Mirs Bay. Firstly,
      Spearman's rank correlation-based network analysis was conducted as the first
      step to identify the co-occurrence correlations of metals from raw metadata, and
      then for further analysis using the normalized metadata. The correlations
      patterns obtained by network were consistent with those obtained by the other
      statistic normalization methods, including annual ratios, R-squared coefficient
      and Pearson correlation coefficient. Both Deep Bay and Victoria Harbour have been
      polluted by heavy metals, especially for Pb and Cu, which showed strong co
      occurrence with other heavy metals (e.g. Cr, Ni, Zn and etc.) and little
      correlations with the reference parameters (Fe or Al). For Mirs Bay, which has
      better marine sediment quality compared with Deep Bay and Victoria Harbour, the
      co-occurrence patterns revealed by network analysis indicated that the metals in
      sediment dominantly followed the natural geography process. Besides the wide
      applications in biology, sociology and informatics, it is the first time to apply
      network analysis in the researches of environment pollutions. This study
      demonstrated its powerful application for revealing the co-occurrence
      correlations among heavy metals in marine sediments, which could be further
      applied for other pollutants in various environment systems. 

PMID- 24559935
TI  - The impact of temperature stress and pesticide exposure on mortality and disease
      susceptibility of endangered Pacific salmon.
AB  - Anthropogenic stressors, including chemical contamination and temperature stress,
      may contribute to increased disease susceptibility in aquatic animals.
      Specifically, the organophosphate pesticide malathion has been detected in
      surface waters inhabited by threatened and endangered salmon. In the presence of
      increasing water temperatures, malathion may increase susceptibility to disease
      and ultimately threaten salmon survival. This work examines the effect of acute
      and sublethal exposures to malathion on ocean-type subyearling Chinook salmon
      held under two temperature regimes. Chinook salmon were exposed to malathion at
      optimal (11  degrees C) or elevated (19 and 20  degrees C) temperatures. The
      influence of temperature on the acute toxicity of malathion was determined by
      generating 96-h lethal concentration (LC) curves. A disease challenge assay was
      also used to assess the effects of sublethal malathion exposure. The malathion
      concentration that resulted in 50% mortality (LC50; 274.1 MUg L(-1)) of the
      Chinook salmon at 19  degrees C was significantly less than the LC50 at 11 
      degrees C (364.2 MUg L(-1)). Mortality increased 11.2% in Chinook salmon exposed
      to malathion at the elevated temperature and challenged with Aeromonas
      salmonicida compared to fish held at the optimal temperature and exposed to
      malathion or the carrier control. No difference in disease challenge mortality
      was observed among malathion-exposed and unexposed fish at the optimal
      temperature. The interaction of co-occurring stressors may have a greater impact
      on salmon than if they occur in isolation. Ecological risk assessments
      considering the effects of an individual stressor on threatened and endangered
      salmon may underestimate risk when additional stressors are present in the
      environment.

PMID- 24559936
TI  - Stable carbon isotope analysis to distinguish biotic and abiotic degradation of
      1,1,1-trichloroethane in groundwater sediments.
AB  - The fate and treatability of 1,1,1-TCA by natural and enhanced reductive
      dechlorination was studied in laboratory microcosms. The study shows that
      compound-specific isotope analysis (CSIA) identified an alternative 1,1,1-TCA
      degradation pathway that cannot be explained by assuming biotic reductive
      dechlorination. In all biotic microcosms 1,1,1-TCA was degraded with no apparent
      increase in the biotic degradation product 1,1-DCA. 1,1,1-TCA degradation was
      documented by a clear enrichment in (13)C in all biotic microcosms, but not in
      the abiotic control, which suggests biotic or biotically mediated degradation.
      Biotic degradation by reductive dechlorination of 1,1-DCA to CA only occurred in
      bioaugmented microcosms and in donor stimulated microcosms with low initial 1,1,1
      TCA or after significant decrease in 1,1,1-TCA concentration (after~day 200).
      Hence, the primary degradation pathway for 1,1,1-TCA does not appear to be
      reductive dechlorination via 1,1-DCA. In the biotic microcosms, the degradation
      of 1,1,1-TCA occurred under iron and sulfate reducing conditions. Biotic
      reduction of iron and sulfate likely resulted in formation of FeS, which can
      abiotically degrade 1,1,1-TCA. Hence, abiotic degradation of 1,1,1-TCA mediated
      by biotic FeS formation constitute an explanation for the observed 1,1,1-TCA
      degradation. This is supported by a high 1,1,1-TCA (13)C enrichment factor
      consistent with abiotic degradation in biotic microcosms. 1,1-DCA carbon isotope
      field data suggest that this abiotic degradation of 1,1,1-TCA is a relevant
      process also at the field site. 

PMID- 24559937
TI  - Pharmacological examination of TCM should be evidence based.

PMID- 24559938
TI  - [Ectopic supernumerary kidney. A casual finding].

PMID- 24559939
TI  - A rare case of thyroid paraganglioma detected by 18F-FDG PET/CT.

PMID- 24559941
TI  - Liquid scintillation counting of polycarbonates: a sensitive technique for
      measurement of activity concentration of some radioactive noble gases.
AB  - This work explores the application of the liquid scintillation counting of
      polycarbonates for measurement of the activity concentration of radioactive noble
      gases. Results from experimental studies of the method are presented. Potential
      applications in the monitoring of radioactive noble gases are discussed. 

PMID- 24559940
TI  - Pilot clinical study of boron neutron capture therapy for recurrent hepatic
      cancer involving the intra-arterial injection of a (10)BSH-containing WOW
      emulsion.
AB  - A 63-year-old man with multiple HCC in his left liver lobe was enrolled as the
      first patient in a pilot study of boron neutron capture therapy (BNCT) involving
      the selective intra-arterial infusion of a (10)BSH-containing water-in-oil-in
      water emulsion ((10)BSH-WOW). The size of the tumorous region remained stable
      during the 3 months after the BNCT. No adverse effects of the BNCT were observed.
      The present results show that (10)BSH-WOW can be used as novel intra-arterial
      boron carriers during BNCT for HCC. 

PMID- 24559942
TI  - "Please Sir, I want some more?"... Charles Dickens, Oliver Twist.

PMID- 24559943
TI  - Abnormal nutrition affects waitlist mortality in infants awaiting heart
      transplant.
AB  - BACKGROUND: Although nutritional status affects survival after heart transplant
      (HTx) in adults and older children, its effect on outcomes in young children is
      unknown. This study aimed to assess the effect of pre-HTx nutrition on outcomes
      in this population. METHODS: Children aged 0 to 2 years old listed for HTx from
      1997 to 2011 were identified from the Organ Procurement and Transplantation
      Network database. Nutritional status was classified according to percentage of
      ideal body weight at listing and at HTx. Logistic regression analysis evaluated
      the risk of waitlist mortality. Cox proportional hazard models assessed the
      effect of nutrition on post-HTx survival. RESULTS: Of 1,653 children evaluated,
      899 (54%) had normal nutrition at listing, 445 (27%) were mildly wasted, 203
      (12%) were moderate or severely wasted, and 106 (6%) had an elevated weight-to
      height (W:H) ratio. Moderate or severe wasting (adjusted odds ratio, 1.9; 95%
      confidence interval, 1.3-2.7) and elevated W:H (adjusted odds ratio, 1.7; 95%
      confidence interval, 1.1-2.6) were independent risk factors for waitlist
      mortality. HTx was performed in 1,167 patients, and 1,016 (87%) survived to 1
      year post-HTx. Nutritional status at listing or at HTx was not associated with
      increased post-HTx mortality. Nutritional status did not affect the need for
      early reoperation, dialysis, or the incidences of infection, stroke, or rejection
      before hospital discharge. CONCLUSIONS: Moderate or severe wasting and an
      elevated W:H are independent risk factors for waitlist mortality in patients aged
      < 2 years but do not affect post-HTx mortality. Optimization of pre-HTx
      nutritional status constitutes a strategy to reduce waitlist mortality in this
      age range.

PMID- 24559944
TI  - Survival in patients removed from the heart transplant waiting list before
      receiving a transplant.
AB  - BACKGROUND: Little is known about the outcomes in patients who are removed from
      the heart transplant (HT) waiting list before receiving a transplant. We sought
      to analyze outcomes in such patients in the United States (U.S.) in the current
      era. METHODS: All patients aged >= 18 years old listed for a primary HT in the
      U.S. between July 2004 and September 2010 were identified. Outcomes in those
      removed from the list by March 2011 (survival, relisting, HT) were examined using
      time-to-event analyses. RESULTS: Of 15,061 patients listed for primary HT, 10,168
      (68%) received a HT, 1,393 (9%) died on the waiting list, and 1,871(12%) were
      removed before receiving HT. Of patients removed from the list, 560 (30%) were
      removed due to clinical improvement, 692 (37%) due to deterioration, and 619
      (33%) due to other reasons. After removal, 30-day and 1-year survival were 99.6%
      and 94%, respectively, in patients removed due to improvement and 44% and 26%,
      respectively, in patients removed due to deterioration. Multivariable predictors
      of death after removal were removal due to clinical deterioration, hypertrophic
      or restrictive cardiomyopathy, United Network of Organ Sharing status 1A/1B at
      listing, and renal dysfunction. Only 27 patients (4.8%) among those removed due
      to improvement, 21 (3.0%) removed due to deterioration, and 46 (7.4%) removed due
      to other reasons were relisted. CONCLUSIONS: One in 8 patients listed for HT in
      the U.S. are removed from the waiting list before receiving HT. The indication
      for removal (clinical deterioration vs improvement) is the strongest independent
      predictor of survival after removal from the list.

PMID- 24559945
TI  - Invasive aspergillosis among heart transplant recipients: a 24-year perspective.
AB  - BACKGROUND: Invasive aspergillosis is a well-known complication in severely
      immunosuppressed patients, including heart transplant recipients, and associated
      mortality is high. Despite the severity of the disease in this population, few
      recent series with secular trends have addressed the problem. METHODS: We
      performed a descriptive study of 479 consecutive heart transplant recipients from
      1988 to 2011 in a single institution. RESULTS: Overall invasive aspergillosis
      incidence in heart transplant recipients was 6.5% (31 of 479). Incidence
      decreased from 8.7% (24 of 277) in the period 1988 to 2000 (historical cohort) to
      3.5% (7 of 202) afterward (p = 0.02); 4 of the 7 cases were in the context of an
      outbreak. The most common presentation was lung infection, but episodes occurring
      >3 months after transplantation (late aspergillosis) showed a higher frequency of
      disseminated disease and involvement of the central nervous system and of
      atypical sites compared with early (first 3 months) episodes. Related mortality
      was 36%, with a significant decrease between the historical cohort and the
      present cohort: 46% vs 0% (p = 0.04) and a trend toward lower related death in
      early vs late cases (26% vs 63%, p = 0.09). CONCLUSIONS: In our series, both
      incidence and mortality associated with invasive aspergillosis in heart
      transplant recipients showed a decrease in recent years. Careful environmental
      management and targeted anti-fungal prophylaxis may minimize the incidence of
      invasive aspergillosis in this setting.

PMID- 24559947
TI  - Plasma DNA levels of Torque teno virus and immunosuppression after lung
      transplantation.

PMID- 24559946
TI  - Low cardiac output associated with ventricular tachyarrhythmias in continuous
      flow LVAD recipients with a concomitant ICD (LoCo VT Study).

PMID- 24559948
TI  - Late manifestation of a driveline infection after heart transplantation.

PMID- 24559949
TI  - John H Gibbon Jr Lecture. Extracorporeal life support: Gibbon fulfilled.

PMID- 24559950
TI  - Is the use of prosthetic mesh recommended in severely obese patients undergoing
      concomitant abdominal wall hernia repair and sleeve gastrectomy?
AB  - BACKGROUND: The concomitant use of nonabsorbable mesh during stapled bariatric
      surgery has been discouraged due to potential contamination. The aim of our study
      was to compare and quantify the extent of bacterial load and gross contamination
      of the peritoneal cavity in patients undergoing laparoscopic sleeve gastrectomy
      (LSG) vs those undergoing laparoscopic Roux-en-Y gastric bypass (LRYGB). STUDY
      DESIGN: We prospectively enrolled all patients undergoing LSG and LRYGB.
      Peritoneal fluid aspirate samples were collected from each subject. Sample A was
      obtained at the beginning of the procedure, and sample B was obtained at the end
      of the procedure either from the staple line wash of the LSG or the
      gastrojejunostomy in the LRYGB. RESULTS: A total of 77 patients (51 LSG and 26
      LRYGB) and 154 samples (102 from LSG and 52 from LRYGB) were included in this
      study. All samples obtained at the beginning of each procedure (sample A) were
      culture negative. Samples of peritoneal fluid obtained at the end of the
      procedure (sample B) in sleeve gastrectomy procedures were all negative (0%)
      after a minimum of 72 hours for aerobic and anaerobic cultures. Those obtained
      for LRYGB (sample B) were culture positive in 4 of 26 (15%). The latter results
      are statistically significant (p < 0.05). CONCLUSIONS: Intraperitoneal bacterial
      cultures in patients undergoing LSG are negative, contrary to those in patients
      undergoing LRYGB. The concomitant use of prosthetic material to repair ventral
      hernias in patients undergoing an LSG procedure should be safe and feasible.

PMID- 24559951
TI  - Prospective evaluation of surgeon physical examination for detection of
      incisional hernias.
AB  - BACKGROUND: Surgeon physical examination is often used to monitor for hernia
      recurrence in clinical and research settings, despite a lack of information on
      its effectiveness. This study aims to compare surgeon-reviewed CT with surgeon
      physical examination for the detection of incisional hernia. STUDY DESIGN:
      General surgery patients with an earlier abdominal operation and a recent
      viewable CT scan of the abdomen and pelvis were enrolled prospectively. Patients
      with a stoma, fistula, or soft-tissue infection were excluded. Surgeon-reviewed
      CT was treated as the gold standard. Patients were stratified by body mass index
      into nonobese (body mass index <30) and obese groups. Testing characteristics and
      real-world performance, including positive predictive value and negative
      predictive value, were calculated. RESULTS: One hundred and eighty-one patients
      (mean age 54 years, 68% female) were enrolled. Hernia prevalence was 55%. Mean
      area of hernias was 44.6 cm(2). Surgeon physical examination had a low
      sensitivity (77%) and negative predictive value (77%). This difference was more
      pronounced in obese patients, with sensitivity of 73% and negative predictive
      value 69%. CONCLUSIONS: Surgeon physical examination is inferior to CT for
      detection of incisional hernia, and fails to detect approximately 23% of hernias.
      In obese patients, 31% of hernias are missed by surgeon physical examination.
      This has important implications for clinical follow-up and design of studies
      evaluating hernia recurrence, as ascertainment of this result must be reliable
      and accurate.

PMID- 24559952
TI  - Laparoscopic resection of gastric and small bowel gastrointestinal stromal
      tumors: 10-year experience at a single center.
AB  - BACKGROUND: Complete curative resection remains the treatment of choice for
      nonmetastatic gastrointestinal stromal tumors (GISTs). The safety and feasibility
      of laparoscopy in the treatment of this disease has been shown, however, the long
      term oncologic outcomes of this technique remain unclear. STUDY DESIGN: An
      ongoing prospectively maintained database including all laparoscopically resected
      gastric and small bowel GISTs (n = 116) at Mount Sinai Medical Center from July
      1999 to December 2011 was retrospectively analyzed. Recurrence and survival
      outcomes were calculated using the Kaplan-Meier method and compared with log-rank
      test. RESULTS: Tumors were of gastric (77.6%) and small bowel (22.4%) origins.
      Overall mean tumor size was 4.0 cm (+/-2.7 cm) and R0 resection was achieved in
      113 (97.4%) cases. Overall perioperative complication rate was 14.7%, with a
      reoperative rate of 4.3% at 90 days. When comparing gastric with small bowel
      GISTs, a more acute presentation requiring emergent resections was noted in
      patients with small bowel GISTs (p = 008). However tumor size, operative data,
      and perioperative outcomes were comparable in both groups (p = NS). At a median
      follow-up of 56.4 months (range 0.1 to 162.4 months), recurrence rate was 7.8%
      and comparable in both gastric and small bowel GISTs (p = NS). Risk factors for
      recurrence on univariate analysis were presence of ulceration/necrosis (p <
      0.001) and tumor size >5 cm (p = 0.05). Overall 10-year survival rate was 90.8%.
      Gastric and small bowel overall survival rates were similar (90.7% vs 91.3%,
      respectively). Overall 10-year disease-free survival was 80.0% (84.3% gastric vs
      71.6% small bowel; p = NS). CONCLUSIONS: Our series demonstrates the safety and
      feasibility of laparoscopy in patients undergoing resection of small bowel and
      gastric GISTs. Comparable long-term oncologic outcomes with a 10-year survival of
      90.8% were achieved.

PMID- 24559953
TI  - Adjuvant radiotherapy in centrally located hepatocellular carcinomas after
      hepatectomy with narrow margin (<1 cm): a prospective randomized study.
AB  - BACKGROUND: Although radiotherapy (RT) provides potential benefits for patients
      with hepatocellular carcinomas (HCCs) that are unsuitable for operation, the
      specific role of adjuvant RT in HCC after hepatectomy remains ill defined. The
      current study's aim was to evaluate the safety and efficacy of adjuvant RT for
      centrally located HCCs after narrow-margin (<1 cm) hepatectomy. STUDY DESIGN: The
      study included 119 patients with centrally located HCCs who underwent narrow
      margin hepatectomy between July 2007 and March 2012. Patients were prospectively
      randomized to receive adjuvant RT (n = 58) or were assigned to a control group (n
      = 61). Surgical outcomes, safety, and survival rates were evaluated. RESULTS:
      Hepatectomy was successfully performed in all patients. No cases of radiation
      induced liver disease were observed. One-, 3-, and 5-year recurrence-free
      survival rates were 78.1%, 56.5%, and 36.9% in the adjuvant RT group and 72.4%,
      40.1%, and 16.0% in the control group, respectively (p = 0.06, log-rank test).
      Corresponding overall survival rates were 96.2%, 72.6%, 48.4%, and 89.6%, 74.5%,
      37.2%, respectively (p = 0.48, log-rank test). One-, 3-, and 5-year recurrence
      free survival rates in patients with small-diameter tumors (<=5 cm) were 88.8%,
      67.4%, 42.9% in the adjuvant RT group and 82.3%, 42.9%, 21.5% in the control
      group (p = 0.03, log-rank test). Corresponding overall survival rates were 97.5%,
      75.3%, 75.3%, and 94.7%, 84.1%, 65.4%, respectively (p = 0.92, log-rank test).
      CONCLUSIONS: Adjuvant RT for centrally located HCCs after narrow-margin
      hepatectomy was technically feasible and relatively safe. No significant between
      group difference was observed in recurrence-free and overall survival. The post
      hoc subgroup comparison showed that adjuvant RT improved recurrence-free survival
      considerably, but not overall survival, in patients with small HCCs (<=5 cm).
      More in-depth studies are needed to validate this finding.

PMID- 24559954
TI  - Racial disparities in readmissions and site of care for major surgery.
AB  - BACKGROUND: Racial disparities have been described in many surgical outcomes. We
      sought to examine whether these disparities extend to postoperative readmission
      rates and whether the disparities are associated with differences in patient mix
      and/or hospital-level differences. STUDY DESIGN: National Medicare beneficiaries
      undergoing operations in 3 different specialties from 2006 to 2008 were examined:
      colectomy, hip replacement, and coronary artery bypass grafting (CABG) (n =
      798,279). Our outcome measure was risk-adjusted 30-day readmission. We first used
      logistic regression to adjust for patient factors. We then stratified hospitals
      into quintiles according to the proportion of black patients treated and examined
      the differences in readmission rates between blacks and whites. Finally, we used
      fixed effects regression models that further adjust for the hospital to explore
      whether the disparity was attenuated after accounting for hospital differences.
      RESULTS: Black patients were readmitted more often after all 3 operations
      compared with white patients. The unadjusted odds ratio (OR) for readmission for
      all 3 operations combined was 1.25 (95% CI 1.22 to 1.28) (colectomy OR 1.17, 95%
      CI 1.13 to 1.22; hip replacement OR 1.20, 95% CI 1.14 to 1.27; CABG OR 1.25, 95%
      CI 1.19 to 1.30). Adjusting for patient factors explained 36% of the disparity
      for all 3 operations (35% for colectomy, 0% for hip replacement, and 32% for
      CABG), but in analysis that adjusts for hospital differences, we found that the
      hospitals where care was received also explained 28% of the disparity (35% for
      colectomy, 70% for hip replacement and 20% for CABG). CONCLUSIONS: Black patients
      are significantly more likely to be readmitted to the hospital after major
      surgery compared with white patients. This disparity was attenuated after
      adjusting for patient factors as well as hospital differences.

PMID- 24559955
TI  - Increasing age and survival after orthotopic liver transplantation for patients
      with hepatocellular cancer.
AB  - BACKGROUND: Orthotopic liver transplantation (OLT) is the gold standard treatment
      for patients with early hepatocellular carcinoma (HCC). There are concerns about
      the efficacy of OLT for HCC in older patients, who we hypothesized might have
      poorer outcomes. Therefore, we sought to examine advanced age and its impact on
      OLT outcomes. STUDY DESIGN: The United Network for Organ Sharing database was
      queried for patients who underwent OLT for HCC from 1987 to 2009. Patients were
      divided into 3 age groups: 35 to 49 years old, 50 to 64 years old, and 65 years
      or older, and patient characteristics were compared. Univariate and multivariate
      analyses were performed to assess the impact of age on OLT outcomes. RESULTS: Of
      10,238 patients with OLT for HCC, 16.5% (n = 1,688) of patients were 35 to 49
      years old, 67.8% (n = 6,937) were 35 to 49 years old, and 15.8% (n = 1,613) were
      65 years and older. By Kaplan-Meier method, the 50- to 64-year-old age group had
      the highest overall survival, despite having one of the highest rates of
      hepatitis C positivity (70%), but this group also had the lowest rate of diabetes
      mellitus (8.7%). The lowest overall survival was observed in the 65-year or older
      age group (p < 0.001). Finally, there was no difference in disease-specific
      survival among the age groups (p = 0.858), and patients aged 65 years and older
      had the highest rate of death from nonhepatic causes (17.5%). CONCLUSIONS:
      Although OS was prolonged in younger patients who underwent OLT for HCC, there
      was no observed difference in disease-specific survival among the age groups. Our
      results suggest that carefully selected patients 65 years of age and older can
      derive equal benefit from OLT for HCC when compared with their younger
      counterparts.

PMID- 24559957
TI  - Hartford Consensus: a call to action for THREAT, a medical disaster preparedness
      concept.

PMID- 24559956
TI  - Survival in the elderly after pneumonectomy for early-stage non-small cell lung
      cancer: a comparison with nonoperative management.
AB  - BACKGROUND: Short-term outcomes of morbidity, mortality, and quality of life
      after pneumonectomy worsen with increasing age. The impact of age on long-term
      outcomes has not been well described. The purpose of this study was to quantify
      the impact of patient age on long-term survival after pneumonectomy for early
      stage non-small cell lung cancer. STUDY DESIGN: Overall survival (OS) of patients
      who had a pneumonectomy for stage I to II non-small cell lung cancer in the
      Surveillance Epidemiology and End Results program registry from 1988 through 2010
      was evaluated using multivariable and propensity score adjusted Cox proportional
      hazard models. Age was stratified as younger than 50 years, 50 to 69 years, 70 to
      79 years, and 80 years and older. Pneumonectomy patients' OS was compared with
      matched patients who refused surgery and underwent radiation therapy (RT).
      RESULTS: Pneumonectomies comprised 10.8% of non-small cell lung cancer resections
      in 1988, but only 2.9% in 2010. Overall, 5-year OS of 5,701 pneumonectomy
      patients was 49.8% (95% CI, 45.3-54.8%) for patients younger than 50 years, 40.5%
      (95% CI, 38.8-42.2%) for patients 50 to 69 years, 28.9% (95% CI, 26.6-31.5%) for
      patients 70 to 79 years, and 18.8% (95% CI, 14.2-24.8%) for patients 80 and older
      (p < 0.001). Increasing patient age was the most important predictor of worse OS
      (hazard ratio = 1.34 per decade; p < 0.001). For patients younger than 70 years,
      5-year OS was 46.3% (95% CI, 36.2-59.2%) after pneumonectomy vs 18.4% (95% CI,
      11.9-28.3%) for matched RT patients (p < 0.001). In matched groups of patients 70
      years and older, 5-year OS for pneumonectomy was 25.8% (95% CI, 20.8-32.0%) vs
      12.2% for RT (95% CI, 8.6-17.4%; p = 0.02). CONCLUSIONS: Survival after
      pneumonectomy for stage I to II non-small cell lung cancer decreases steadily
      with patient age. The incremental benefit of pneumonectomy vs RT in matched
      patients is less in patients older than 70 years than in younger patients,
      although outcomes with pneumonectomy are superior to RT in all age groups.
      Patients should not be denied pneumonectomy based on age alone, but careful
      patient selection in elderly patients is essential to optimize survival.

PMID- 24559958
TI  - Joint Committee to Create a National Policy to Enhance Survivability from Mass
      Casualty Shooting Events: Hartford Consensus II.

PMID- 24559959
TI  - What is the preferred surgery for perforated left-sided diverticulitis?

PMID- 24559960
TI  - Jumping the gun? Evaluating the evidence for synthetic mesh in contaminated
      hernia repairs.

PMID- 24559961
TI  - Hepatectomy without endotracheal general anesthesia: a safe procedure?

PMID- 24559962
TI  - Reply: To PMID 23490541.

PMID- 24559963
TI  - Defining surgical quality in gastric cancer: is it time to include ethnicity?

PMID- 24559964
TI  - Reply: To PMID 23664139.

PMID- 24559965
TI  - Pedicled cross-leg flaps.

PMID- 24559966
TI  - Reply: To PMID 23890841.

PMID- 24559968
TI  - A cost-effective technique for laparoscopic appendectomy: outcomes and costs of a
      case-control prospective single-operator study of 112 unselected consecutive
      cases of complicated acute appendicitis.

PMID- 24559969
TI  - Intracorporeal circular-stapled esophagojejunostomy after laparoscopic total
      gastrectomy: a novel self-pulling and holding purse-string suture technique.

PMID- 24559970
TI  - Fully robotic-assisted technique for total pancreatectomy with an autologous
      islet transplant in chronic pancreatitis patients: results of a first series.

PMID- 24559971
TI  - Role of melatonin on production and preservation of gametes and embryos: a brief
      review.
AB  - The aim of this brief review is to clarify the role of melatonin in the
      production and preservation of mammalian gametes and embryos. Melatonin is an
      indoleamine synthesized from tryptophan in the pineal gland and other organs that
      operates as a hypothalamic-pituitary-gonadal axis modulator and regulates the
      waxing and waning of seasonal reproductive competence in photoperiodic mammals. A
      major function of the melatonin rhythm is to transmit information about the
      length of the daily photoperiod to the circadian and circannual systems in order
      to provide time-of-day and time-of-year information, respectively, to the
      organism. Melatonin is also a powerful antioxidant and anti-apoptotic agent,
      which is due to its direct scavenging of toxic oxygen derivatives and its ability
      to reduce the formation of reactive species. Mammalian gametes and embryos are
      highly vulnerable to oxidative stress due to the presence of high lipid levels;
      during artificial breeding procedures, these structures are exposed to dramatic
      changes in the microenvironment, which have a direct bearing on their function
      and viability. Free radicals influence the balance between oxidation-reduction
      reactions, disturb the transbilayer-phospholipid asymmetry of the plasma membrane
      and enhance lipid peroxidation. Melatonin, due to its amphiphilic nature, is
      undoubtedly useful in tissues by protecting them from free radical-mediated
      oxidative damage and cellular death. The supplementation of melatonin to semen
      extender or culture medium significantly improves sperm viability, oocyte
      competence and blastocyst development in vitro. 

PMID- 24559972
TI  - Ad libitum feeding during the peripartal period affects body condition,
      reproduction results and metabolism of sows.
AB  - To overcome negative energy balance during the peripartal period of sows, an ad
      libitum feeding strategy (ADLIB) as alternative for commonly used restricted
      feeding (STANDARD, on average 3kg feed/day) was evaluated. Plasma metabolites and
      thyroid hormones, change of back fat thickness (BF), reproductive traits, and
      piglet performance were monitored. Voluntary feed intake of ADLIB sows declined
      at farrowing but was still more than twice the amount of what was offered to
      STANDARD sows. Consequently, ADLIB sows lost less BF than STANDARD sows
      (P=0.041). Additionally, BF change was affected by body condition. LEAN sows
      (BF<18mm on d 105 of gestation) lost less BF than MODERATE sows (18mm<=BF<=22mm)
      which lost less BF than FAT sows (BF>22mm) (P<0.001). Except for a decreased
      percentage of stillborn piglets for MODERATE sows (P=0.044), reproduction results
      were not affected. Piglet weaning weight of ADLIB-FAT and STANDARD-MODERATE sows
      was reduced in comparison with that of ADLIB-LEAN sows (P=0.005). Regardless of
      body condition, all metabolites and thyroid hormones measured showed a time
      dependent profile (P<0.001). On d 112 of gestation increased concentrations of
      creatinine (P=0.004), non-esterified fatty acids (P=0.039), and serum crosslaps
      (P=0.016) for STANDARD sows were observed. Triglycerides were increased for FAT
      sows (P<0.001), and decreased faster over time for ADLIB (P=0.013) and for FAT
      (P=0.012). Although ad libitum feeding during the peripartal period only resulted
      in less mobilization of muscle, fat, and bone reserves on d 112 of gestation,
      results of BF change and piglet weaning weight indicated that ad libitum feeding
      is beneficial for sow performance provided that BF is below 22mm. 

PMID- 24559974
TI  - Comment on: The effect of laparoscopic sleeve gastrectomy with or without hiatal
      hernia repair on gastroesophageal reflux disease in obese patients.

PMID- 24559973
TI  - Acceptability, language, and structure of text message-based behavioral
      interventions for high-risk adolescent females: a qualitative study.
AB  - PURPOSE: To elucidate key elements surrounding acceptability/feasibility,
      language, and structure of a text message-based preventive intervention for high
      risk adolescent females. METHODS: We recruited high-risk 13- to 17-year-old
      females screening positive for past-year peer violence and depressive symptoms,
      during emergency department visits for any chief complaint. Participants
      completed semistructured interviews exploring preferences around text message
      preventive interventions. Interviews were conducted by trained interviewers,
      audio-recorded, and transcribed verbatim. A coding structure was iteratively
      developed using thematic and content analysis. Each transcript was double coded.
      NVivo 10 was used to facilitate analysis. RESULTS: Saturation was reached after
      20 interviews (mean age 15.4; 55% white; 40% Hispanic; 85% with cell phone
      access). (1) Acceptability/feasibility themes: A text-message intervention was
      felt to support and enhance existing coping strategies. Participants had a few
      concerns about privacy and cost. Peer endorsement may increase uptake. (2)
      Language themes: Messages should be simple and positive. Tone should be
      conversational but not slang filled. (3) Structural themes: Messages may be
      automated but must be individually tailored on a daily basis. Both predetermined
      (automatic) and as-needed messages are requested. Dose and timing of content
      should be varied according to participants' needs. Multimedia may be helpful but
      is not necessary. CONCLUSIONS: High-risk adolescent females seeking emergency
      department care are enthusiastic about a text message-based preventive
      intervention. Incorporating thematic results on language and structure can inform
      development of future text messaging interventions for adolescent girls. Concerns
      about cost and privacy may be able to be addressed through the process of
      recruitment and introduction to the intervention.

PMID- 24559975
TI  - Management of regional metastatic disease in head and neck cutaneous malignancy.
      1. Cutaneous squamous cell carcinoma.
AB  - This overview is the first of 2 articles on the current evidence for management
      of the neck and parotid in cutaneous cancers of the head and neck. In this paper
      we discuss cutaneous squamous cell carcinoma (SCC) and review the latest evidence
      for management of the regional nodes. 

PMID- 24559976
TI  - Effects of Lactobacillus rhamnosus LA68 on the immune system of C57BL/6 mice upon
      oral administration.
AB  - Probiotic bacteria have been used in human nutrition for centuries and are now
      attracting more attention. In order to examine the immunological aspects of
      probiotic consumption, Lactobacillus rhamnosus LA68 was orally administrated
      using gavage to healthy C57BL/6 mice. After one month splenocytes were isolated,
      and analysed by flow cytometry. The magnitude of splenocyte proliferation upon
      stimulation with lipopolysaccharide and peptidoglycan and cytokine levels (IFN
      gamma, IL-6, IL-10 and IL-17) was assessed. Cytokine levels in the serum were
      also analysed. Oral application of strain LA68 leads to a significant decrease of
      CD3+, CD25+ and CD19+ cells, and an increase of CD11b+ and CD16/CD32+ positive
      cell populations in the mouse spleen. Increased sensitivity to stimulation
      through proliferation and IL-6 secretion was detected. Increased serum IFN-gamma
      and decreased IL-10 levels were found. Our results show increased responsiveness
      of splenocytes, activation of the Th1 type of immune response, and a shift of
      leucocyte populations towards monocyte/granulocyte populations. 

PMID- 24559977
TI  - SAXS/SANS probe of intermolecular interactions in concentrated protein solutions.

PMID- 24559978
TI  - Does ephaptic coupling contribute to propagation in cardiac tissue?

PMID- 24559979
TI  - Mechanically guided cell migration: less of a stretch than ever.

PMID- 24559980
TI  - How accurately can a single receptor measure ligand concentrations?

PMID- 24559981
TI  - Diffusion coefficients of endogenous cytosolic proteins from rabbit skinned
      muscle fibers.
AB  - Efflux time courses of endogenous cytosolic proteins were obtained from rabbit
      psoas muscle fibers skinned in oil and transferred to physiological salt
      solution. Proteins were separated by gel electrophoresis and compared to load
      matched standards for quantitative analysis. A radial diffusion model
      incorporating the dissociation and dissipation of supramolecular complexes
      accounts for an initial lag and subsequent efflux of glycolytic and
      glycogenolytic enzymes. The model includes terms representing protein crowding,
      myofilament lattice hindrance, and binding to the cytomatrix. Optimization
      algorithms returned estimates of the apparent diffusion coefficients, D(r,t),
      that were very low at the onset of diffusion (~10(-10) cm(2) s(-1)) but increased
      with time as cytosolic protein density, which was initially high, decreased.
      D(r,t) at later times ranged from 2.11 * 10(-7) cm(2) s(-1) (parvalbumin) to 0.20
      * 10(-7) cm(2) s(-1) (phosphofructose kinase), values that are 3.6- to 12.3-fold
      lower than those predicted in bulk water. The low initial values are consistent
      with the presence of complexes in situ; the higher later values are consistent
      with molecular sieving and transient binding of dissociated proteins. Channeling
      of metabolic intermediates via enzyme complexes may enhance production of
      adenosine triphosphate at rates beyond that possible with randomly and/or
      sparsely distributed enzymes, thereby matching supply with demand. 

PMID- 24559982
TI  - Mechanism of calponin stabilization of cross-linked actin networks.
AB  - The actin-binding protein calponin has been previously implicated in actin
      cytoskeletal regulation and is thought to act as an actin stabilizer, but the
      mechanism of its function is poorly understood. To investigate this underlying
      physical mechanism, we studied an in vitro model system of cross-linked actin
      using bulk rheology. Networks with basic calponin exhibited a delayed onset of
      strain stiffening (10.0% without calponin, 14.9% with calponin) and were able to
      withstand a higher maximal strain before failing (35% without calponin, 56% with
      calponin). Using fluorescence microscopy to study the mechanics of single actin
      filaments, we found that calponin increased the flexibility of actin filaments,
      evident as a decrease in persistence length from 17.6 MUm without to 7.7 MUm with
      calponin. Our data are consistent with current models of affine strain behavior
      in semiflexible polymer networks, and suggest that calponin stabilization of
      actin networks can be explained purely by changes in single-filament mechanics.
      We propose a model in which calponin stabilizes actin networks against shear
      through a reduction of persistence length of individual filaments. 

PMID- 24559983
TI  - Scaling relationship and optimization of double-pulse electroporation.
AB  - The efficacy of electroporation is known to vary significantly across a wide
      variety of biological research and clinical applications, but as of this writing,
      a generalized approach to simultaneously improve efficiency and maintain
      viability has not been available in the literature. To address that discrepancy,
      we here outline an approach that is based on the mapping of the scaling
      relationships among electroporation-mediated molecular delivery, cellular
      viability, and electric pulse parameters. The delivery of Fluorescein-Dextran
      into 3T3 mouse fibroblast cells was used as a model system. The pulse was
      rationally split into two sequential phases: a first precursor for
      permeabilization, followed by a second one for molecular delivery. Extensive data
      in the parameter space of the second pulse strength and duration were collected
      and analyzed with flow cytometry. The fluorescence intensity correlated linearly
      with the second pulse duration, confirming the dominant role of electrophoresis
      in delivery. The delivery efficiency exhibited a characteristic sigmoidal
      dependence on the field strength. An examination of short-term cell death using 7
      Aminoactinomycin D demonstrated a convincing linear correlation with respect to
      the electrical energy. Based on these scaling relationships, an optimal field
      strength becomes identifiable. A model study was also performed, and the results
      were compared with the experimental data to elucidate underlying mechanisms. The
      comparison reveals the existence of a critical transmembrane potential above
      which delivery with the second pulse becomes effective. Together, these efforts
      establish a general route to enhance the functionality of electroporation. 

PMID- 24559984
TI  - Axonal transport: how high microtubule density can compensate for boundary
      effects in small-caliber axons.
AB  - Long-distance intracellular axonal transport is predominantly microtubule-based,
      and its impairment is linked to neurodegeneration. In this study, we present
      theoretical arguments that suggest that near the axon boundaries (walls), the
      effective viscosity can become large enough to impede cargo transport in small
      (but not large) caliber axons. Our theoretical analysis suggests that this
      opposition to motion increases rapidly as the cargo approaches the wall. We find
      that having parallel microtubules close enough together to enable a cargo to
      simultaneously engage motors on more than one microtubule dramatically enhances
      motor activity, and thus minimizes the effects of any opposition to transport.
      Even if microtubules are randomly placed in axons, we find that the higher
      density of microtubules found in small-caliber axons increases the probability of
      having parallel microtubules close enough that they can be used simultaneously by
      motors on a cargo. The boundary effect is not a factor in transport in large
      caliber axons where the microtubule density is lower. 

PMID- 24559985
TI  - FKBP12.6 activates RyR1: investigating the amino acid residues critical for
      channel modulation.
AB  - We have previously shown that FKBP12 associates with RyR2 in cardiac muscle and
      that it modulates RyR2 function differently to FKBP12.6. We now investigate how
      these proteins affect the single-channel behavior of RyR1 derived from rabbit
      skeletal muscle. Our results show that FKBP12.6 activates and FKBP12 inhibits
      RyR1. It is likely that both proteins compete for the same binding sites on RyR1
      because channels that are preactivated by FKBP12.6 cannot be subsequently
      inhibited by FKBP12. We produced a mutant FKBP12 molecule (FKBP12E31Q/D32N/W59F)
      where the residues Glu(31), Asp(32), and Trp(59) were converted to the
      corresponding residues in FKBP12.6. With respect to the functional regulation of
      RyR1 and RyR2, the FKBP12E31Q/D32N/W59F mutant lost all ability to behave like
      FKBP12 and instead behaved like FKBP12.6. FKBP12E31Q/D32N/W59F activated RyR1 but
      was not capable of activating RyR2. In conclusion, FKBP12.6 activates RyR1,
      whereas FKBP12 activates RyR2 and this selective activator phenotype is
      determined within the amino acid residues Glu(31), Asp(32), and Trp(59) in FKBP12
      and Gln(31), Asn(32), and Phe(59) in FKBP12.6. The opposing but different effects
      of FKBP12 and FKBP12.6 on RyR1 and RyR2 channel gating provide scope for
      diversity of regulation in different tissues. 

PMID- 24559986
TI  - Probing the structure of the mechanosensitive channel of small conductance in
      lipid bilayers with pulsed electron-electron double resonance.
AB  - Mechanosensitive channel proteins are important safety valves against osmotic
      shock in bacteria, and are involved in sensing touch and sound waves in higher
      organisms. The mechanosensitive channel of small conductance (MscS) has been
      extensively studied. Pulsed electron-electron double resonance (PELDOR or DEER)
      of detergent-solubilized protein confirms that as seen in the crystal structure,
      the outer ring of transmembrane helices do not pack against the pore-forming
      helices, creating an apparent void. The relevance of this void to the functional
      form of MscS in the bilayer is the subject of debate. Here, we report PELDOR
      measurements of MscS reconstituted into two lipid bilayer systems: nanodiscs and
      bicelles. The distance measurements from multiple mutants derived from the PELDOR
      data are consistent with the detergent-solution arrangement of the protein. We
      conclude, therefore, that the relative positioning of the transmembrane helices
      is preserved in mimics of the cell bilayer, and that the apparent voids are not
      an artifact of detergent solution but a property of the protein that will have to
      be accounted for in any molecular mechanism of gating. 

PMID- 24559987
TI  - Stochastic fusion simulations and experiments suggest passive and active roles of
      hemagglutinin during membrane fusion.
AB  - Influenza enters the host cell cytoplasm by fusing the viral and host membrane
      together. Fusion is mediated by hemagglutinin (HA) trimers that undergo
      conformational change when acidified in the endosome. It is currently debated how
      many HA trimers, w, and how many conformationally changed HA trimers, q, are
      minimally required for fusion. Conclusions vary because there are three common
      approaches for determining w and q from fusion data. One approach correlates the
      fusion rate with the fraction of fusogenic HA trimers and leads to the conclusion
      that one HA trimer is required for fusion. A second approach correlates the
      fusion rate with the total concentration of fusogenic HA trimers and indicates
      that more than one HA trimer is required. A third approach applies statistical
      models to fusion rate data obtained at a single HA density to establish w or q
      and suggests that more than one HA trimer is required. In this work, all three
      approaches are investigated through stochastic fusion simulations and experiments
      to elucidate the roles of HA and its ability to bend the target membrane during
      fusion. We find that the apparent discrepancies among the results from the
      various approaches may be resolved if nonfusogenic HA participates in fusion
      through interactions with a fusogenic HA. Our results, based on H3 and H1
      serotypes, suggest that three adjacent HA trimers and one conformationally
      changed HA trimer are minimally required to induce membrane fusion (w = 3 and q =
      1). 

PMID- 24559988
TI  - Three-dimensional organization of troponin on cardiac muscle thin filaments in
      the relaxed state.
AB  - Muscle contraction is regulated by troponin-tropomyosin, which blocks and
      unblocks myosin binding sites on actin. To elucidate this regulatory mechanism,
      the three-dimensional organization of troponin and tropomyosin on the thin
      filament must be determined. Although tropomyosin is well defined in electron
      microscopy helical reconstructions of thin filaments, troponin density is mostly
      lost. Here, we determined troponin organization on native relaxed cardiac muscle
      thin filaments by applying single particle reconstruction procedures to
      negatively stained specimens. Multiple reference models led to the same final
      structure, indicating absence of model bias in the procedure. The new
      reconstructions clearly showed F-actin, tropomyosin, and troponin densities. At
      the 25 A resolution achieved, troponin was considerably better defined than in
      previous reconstructions. The troponin density closely resembled the shape of
      troponin crystallographic structures, facilitating detailed interpretation of the
      electron microscopy density map. The orientation of troponin-T and the troponin
      core domain established troponin polarity. Density attributable to the troponin-I
      mobile regulatory domain was positioned where it could hold tropomyosin in its
      blocking position on actin, thus suggesting the underlying structural basis of
      thin filament regulation. Our previous understanding of thin filament regulation
      had been limited to known movements of tropomyosin that sterically block and
      unblock myosin binding sites on actin. We now show how troponin, the Ca(2+)
      sensor, may control these movements, ultimately determining whether muscle
      contracts or relaxes. 

PMID- 24559989
TI  - p15PAF is an intrinsically disordered protein with nonrandom structural
      preferences at sites of interaction with other proteins.
AB  - We present to our knowledge the first structural characterization of the
      proliferating-cell-nuclear-antigen-associated factor p15(PAF), showing that it is
      monomeric and intrinsically disordered in solution but has nonrandom
      conformational preferences at sites of protein-protein interactions. p15(PAF) is
      a 12 kDa nuclear protein that acts as a regulator of DNA repair during DNA
      replication. The p15(PAF) gene is overexpressed in several types of human cancer.
      The nearly complete NMR backbone assignment of p15(PAF) allowed us to measure 86
      N-H(N) residual dipolar couplings. Our residual dipolar coupling analysis reveals
      nonrandom conformational preferences in distinct regions, including the
      proliferating-cell-nuclear-antigen-interacting protein motif (PIP-box) and the
      KEN-box (recognized by the ubiquitin ligase that targets p15(PAF) for
      degradation). In accordance with these findings, analysis of the (15)N R2
      relaxation rates shows a relatively reduced mobility for the residues in these
      regions. The agreement between the experimental small angle x-ray scattering
      curve of p15(PAF) and that computed from a statistical coil ensemble corrected
      for the presence of local secondary structural elements further validates our
      structural model for p15(PAF). The coincidence of these transiently structured
      regions with protein-protein interaction and posttranslational modification sites
      suggests a possible role for these structures as molecular recognition elements
      for p15(PAF). 

PMID- 24559990
TI  - CENP-A arrays are more condensed than canonical arrays at low ionic strength.
AB  - The centromeric histone H3 variant centromeric protein A (CENP-A), whose sequence
      is the least conserved among all histone variants, is responsible for specifying
      the location of the centromere. Here, we present a comprehensive study of CENP-A
      nucleosome arrays by cryo-electron tomography. We see that CENP-A arrays have
      different biophysical properties than canonical ones under low ionic conditions,
      as they are more condensed with a 20% smaller average nearest-neighbor distance
      and a 30% higher nucleosome density. We find that CENP-A nucleosomes have a
      predominantly crossed DNA entry/exit site that is narrowed on average by 8
      degrees , and they have a propensity to stack face to face. We therefore propose
      that CENP-A induces geometric constraints at the nucleosome DNA entry/exit site
      to bring neighboring nucleosomes into close proximity. This specific property of
      CENP-A may be responsible for generating a fundamental process that contributes
      to increased chromatin fiber compaction that is propagated under physiological
      conditions to form centromeric chromatin. 

PMID- 24559991
TI  - Ion counting from explicit-solvent simulations and 3D-RISM.
AB  - The ionic atmosphere around nucleic acids remains only partially understood at
      atomic-level detail. Ion counting (IC) experiments provide a quantitative measure
      of the ionic atmosphere around nucleic acids and, as such, are a natural route
      for testing quantitative theoretical approaches. In this article, we replicate IC
      experiments involving duplex DNA in NaCl(aq) using molecular dynamics (MD)
      simulation, the three-dimensional reference interaction site model (3D-RISM), and
      nonlinear Poisson-Boltzmann (NLPB) calculations and test against recent buffer
      equilibration atomic emission spectroscopy measurements. Further, we outline the
      statistical mechanical basis for interpreting IC experiments and clarify the use
      of specific concentration scales. Near physiological concentrations, MD
      simulation and 3D-RISM estimates are close to experimental results, but at higher
      concentrations (>0.7 M), both methods underestimate the number of condensed
      cations and overestimate the number of excluded anions. The effect of DNA charge
      on ion and water atmosphere extends 20-25 A from its surface, yielding layered
      density profiles. Overall, ion distributions from 3D-RISMs are relatively close
      to those from corresponding MD simulations, but with less Na(+) binding in
      grooves and tighter binding to phosphates. NLPB calculations, on the other hand,
      systematically underestimate the number of condensed cations at almost all
      concentrations and yield nearly structureless ion distributions that are
      qualitatively distinct from those generated by both MD simulation and 3D-RISM.
      These results suggest that MD simulation and 3D-RISM may be further developed to
      provide quantitative insight into the characterization of the ion atmosphere
      around nucleic acids and their effect on structure and stability. 

PMID- 24559992
TI  - Self crowding of globular proteins studied by small-angle x-ray scattering.
AB  - Small-angle x-ray scattering (SAXS) was used to study the behavior of equine
      metmyoglobin (Mb) and bovine pancreatic trypsin inhibitor (BPTI) at
      concentrations up to 0.4 and 0.15 g/mL, respectively, in solutions also
      containing 50% D2O and 1 M urea. For both proteins, significant effects because
      of interference between x-rays scattered by different molecules (interparticle
      interference) were observed, indicating nonideal behavior at high concentrations.
      The experimental data were analyzed by comparison of the observed scattering
      profiles with those predicted by crystal structures of the proteins and a hard
      sphere fluid model used to represent steric exclusion effects. The Mb scattering
      data were well fit by the hard-sphere model using a sphere radius of 18 A, only
      slightly smaller than that estimated from the three-dimensional structure (20 A).
      In contrast, the scattering profiles for BPTI in phosphate buffer displayed
      substantially less pronounced interparticle interference than predicted by the
      hard-sphere model and the radius estimated from the known structure of the
      protein (15 A). Replacing the phosphate buffer with 3-(N-morpolino)propane
      sulfonic acid (MOPS) led to increased interparticle interference, consistent with
      a larger effective radius and suggesting that phosphate ions may mediate
      attractive intermolecular interactions, as observed in some BPTI crystal
      structures, without the formation of stable oligomers. The scattering data were
      also used to estimate second virial coefficients for the two proteins: 2.0 *10(
      4) cm(3)mol/g(2) for Mb in phosphate buffer, 1.6 *10(-4) cm(3)mol/g(2) for BPTI
      in phosphate buffer and 9.2 *10(-4) cm(3)mol/g(2) for BPTI in MOPS. The results
      indicate that the behavior of Mb, which is nearly isoelectric under the
      conditions used, is well described by the hard-sphere model, but that of BPTI is
      considerably more complex and is likely influenced by both repulsive and
      attractive electrostatic interactions. The hard-sphere model may be a generally
      useful tool for the analysis of small-angle scattering data from concentrated
      macromolecular solutions. 

PMID- 24559993
TI  - Minimal effects of macromolecular crowding on an intrinsically disordered
      protein: a small-angle neutron scattering study.
AB  - Small-angle neutron scattering was used to study the effects of macromolecular
      crowding by two globular proteins, i.e., bovine pancreatic trypsin inhibitor and
      equine metmyoglobin, on the conformational ensemble of an intrinsically
      disordered protein, the N protein of bacteriophage lambda. The lambda N protein
      was uniformly labeled with (2)H, and the concentrations of D2O in the samples
      were adjusted to match the neutron scattering contrast of the unlabeled crowding
      proteins, thereby masking their contribution to the scattering profiles.
      Scattering from the deuterated lambda N was recorded for samples containing up to
      0.12 g/mL bovine pancreatic trypsin inhibitor or 0.2 g/mL metmyoglobin. The
      radius of gyration of the uncrowded protein was estimated to be 30 A and was
      found to be remarkably insensitive to the presence of crowders, varying by <2 A
      for the highest crowder concentrations. The scattering profiles were also used to
      estimate the fractal dimension of lambda N, which was found to be ~1.8 in the
      absence or presence of crowders, indicative of a well-solvated and expanded
      random coil under all of the conditions examined. These results are contrary to
      the predictions of theoretical treatments and previous experimental studies
      demonstrating compaction of unfolded proteins by crowding with polymers such as
      dextran and Ficoll. A computational simulation suggests that some previous
      treatments may have overestimated the effective volumes of disordered proteins
      and the variation of these volumes within an ensemble. The apparent insensitivity
      of lambda N to crowding may also be due in part to weak attractive interactions
      with the crowding proteins, which may compensate for the effects of steric
      exclusion. 

PMID- 24559994
TI  - Single-molecule observation of the ligand-induced population shift of rhodopsin,
      a G-protein-coupled receptor.
AB  - Rhodopsin is a G-protein-coupled receptor, in which retinal chromophore acts as
      inverse-agonist or agonist depending on its configuration and protonation state.
      Photostimulation of rhodopsin results in a pH-dependent equilibrium between the
      active state (Meta-II) and its inactive precursor (Meta-I). Here, we monitored
      conformational changes of rhodopsin using a fluorescent probe Alexa594 at the
      cytoplasmic surface, which shows fluorescence increase upon the generation of
      active state, by single-molecule measurements. The fluorescence intensity of a
      single photoactivated rhodopsin molecule alternated between two states.
      Interestingly, such a fluorescence alternation was also observed for ligand-free
      rhodopsin (opsin), but not for dark-state rhodopsin. In addition, the pH
      dependences of Meta-I/Meta-II equilibrium estimated by fluorescence measurements
      deviated notably from estimates based on absorption spectra, indicating that both
      Meta-I and Meta-II are mixtures of two conformers. Our observations indicate that
      rhodopsin molecules intrinsically adopt both active and inactive conformations,
      and the ligand retinal shifts the conformational equilibrium. These findings
      provide dynamical insights into the activation mechanisms of G-protein-coupled
      receptors. 

PMID- 24559995
TI  - Microdomain effects on transverse cardiac propagation.
AB  - The effect of gap junctional coupling, sodium ion channel distribution, and
      extracellular conductivity on transverse conduction in cardiac tissue is explored
      using a microdomain model that incorporates aspects of the inhomogeneous cellular
      structure. The propagation velocities found in our model are compared to those in
      the classic bidomain model and indicate a strong ephaptic microdomain
      contribution to conduction depending on the parameter regime. We show that
      ephaptic effects can be quite significant in the junctional spaces between cells,
      and that the cell activation sequence is modified substantially by these effects.
      Further, we find that transverse propagation can be maintained by ephaptic
      effects, even in the absence of gap junctional coupling. The mechanism by which
      this occurs is found to be cablelike in that the junctional regions act like
      inverted cables. Our results provide insight into several recent experimental
      studies that indirectly indicate a mode of action potential propagation that does
      not rely exclusively on gap junctions. 

PMID- 24559996
TI  - Mechanical boundary conditions bias fibroblast invasion in a collagen-fibrin
      wound model.
AB  - Because fibroblasts deposit the collagen matrix that determines the mechanical
      integrity of scar tissue, altering fibroblast invasion could alter wound healing
      outcomes. Anisotropic mechanical boundary conditions (restraint, stretch, or
      tension) could affect the rate of fibroblast invasion, but their importance
      relative to the prototypical drivers of fibroblast infiltration during wound
      healing--cell and chemokine concentration gradients--is unknown. We tested
      whether anisotropic mechanical boundary conditions affected the directionality
      and speed of fibroblasts migrating into a three-dimensional model wound, which
      could simultaneously expose fibroblasts to mechanical, structural, steric, and
      chemical guidance cues. We created fibrin-filled slits in fibroblast-populated
      collagen gels and applied uniaxial mechanical restraint along the short or long
      axis of the fibrin wounds. Anisotropic mechanical conditions increased the
      efficiency of fibroblast invasion by guiding fibroblasts without increasing their
      migration speed. The migration behavior could be modeled as a biased random walk,
      where the bias due to multiple guidance cues was accounted for in the shape of a
      displacement orientation probability distribution. Taken together, modeling and
      experiments suggested an effect of strain anisotropy, rather than strain-induced
      fiber alignment, on fibroblast invasion.

PMID- 24559997
TI  - Genetic drift suppresses bacterial conjugation in spatially structured
      populations.
AB  - Conjugation is the primary mechanism of horizontal gene transfer that spreads
      antibiotic resistance among bacteria. Although conjugation normally occurs in
      surface-associated growth (e.g., biofilms), it has been traditionally studied in
      well-mixed liquid cultures lacking spatial structure, which is known to affect
      many evolutionary and ecological processes. Here we visualize spatial patterns of
      gene transfer mediated by F plasmid conjugation in a colony of Escherichia coli
      growing on solid agar, and we develop a quantitative understanding by spatial
      extension of traditional mass-action models. We found that spatial structure
      suppresses conjugation in surface-associated growth because strong genetic drift
      leads to spatial isolation of donor and recipient cells, restricting conjugation
      to rare boundaries between donor and recipient strains. These results suggest
      that ecological strategies, such as enforcement of spatial structure and
      enhancement of genetic drift, could complement molecular strategies in slowing
      the spread of antibiotic resistance genes. 

PMID- 24559998
TI  - Mutational robustness accelerates the origin of novel RNA phenotypes through
      phenotypic plasticity.
AB  - Novel phenotypes can originate either through mutations in existing genotypes or
      through phenotypic plasticity, the ability of one genotype to form multiple
      phenotypes. From molecules to organisms, plasticity is a ubiquitous feature of
      life, and a potential source of exaptations, adaptive traits that originated for
      nonadaptive reasons. Another ubiquitous feature is robustness to mutations,
      although it is unknown whether such robustness helps or hinders the origin of new
      phenotypes through plasticity. RNA is ideal to address this question, because it
      shows extensive plasticity in its secondary structure phenotypes, a consequence
      of their continual folding and unfolding, and these phenotypes have important
      biological functions. Moreover, RNA is to some extent robust to mutations. This
      robustness structures RNA genotype space into myriad connected networks of
      genotypes with the same phenotype, and it influences the dynamics of evolving
      populations on a genotype network. In this study I show that both effects help
      accelerate the exploration of novel phenotypes through plasticity. My
      observations are based on many RNA molecules sampled at random from RNA sequence
      space, and on 30 biological RNA molecules. They are thus not only a generic
      feature of RNA sequence space but are relevant for the molecular evolution of
      biological RNA. 

PMID- 24560001
TI  - Simultaneous Raman microspectroscopy and fluorescence imaging of bone
      mineralization in living zebrafish larvae.
AB  - Confocal Raman microspectroscopy and fluorescence imaging are two well
      established methods providing functional insight into the extracellular matrix
      and into living cells and tissues, respectively, down to single molecule
      detection. In living tissues, however, cells and extracellular matrix coexist and
      interact. To acquire information on this cell-matrix interaction, we developed a
      technique for colocalized, correlative multispectral tissue analysis by
      implementing high-sensitivity, wide-field fluorescence imaging on a confocal
      Raman microscope. As a proof of principle, we study early stages of bone
      formation in the zebrafish (Danio rerio) larvae because the zebrafish has emerged
      as a model organism to study vertebrate development. The newly formed bones were
      stained using a calcium fluorescent marker and the maturation process was imaged
      and chemically characterized in vivo. Results obtained from early stages of
      mineral deposition in the zebrafish fin bone unequivocally show the presence of
      hydrogen phosphate containing mineral phases in addition to the carbonated
      apatite mineral. The approach developed here opens significant opportunities in
      molecular imaging of metabolic activities, intracellular sensing, and trafficking
      as well as in vivo exploration of cell-tissue interfaces under (patho
      )physiological conditions. 

PMID- 24560000
TI  - The Berg-Purcell limit revisited.
AB  - Biological systems often have to measure extremely low concentrations of
      chemicals with high precision. When dealing with such small numbers of molecules,
      the inevitable randomness of physical transport processes and binding reactions
      will limit the precision with which measurements can be made. An important
      question is what the lower bound on the noise would be in such measurements.
      Using the theory of diffusion-influenced reactions, we derive an analytical
      expression for the precision of concentration estimates that are obtained by
      monitoring the state of a receptor to which a diffusing ligand can bind. The
      variance in the estimate consists of two terms, one resulting from the intrinsic
      binding kinetics and the other from the diffusive arrival of ligand at the
      receptor. The latter term is identical to the fundamental limit derived by Berg
      and Purcell (Biophys. J., 1977), but disagrees with a more recent expression by
      Bialek and Setayeshgar. Comparing the theoretical predictions against results
      from particle-based simulations confirms the accuracy of the resulting expression
      and reaffirms the fundamental limit established by Berg and Purcell. 

PMID- 24559999
TI  - Modeling of eicosanoid fluxes reveals functional coupling between cyclooxygenases
      and terminal synthases.
AB  - Eicosanoids, including prostaglandins (PG) and leukotrienes, are lipid mediators
      derived from arachidonic acid. A quantitative and biochemical level understanding
      of eicosanoid metabolism would aid in understanding the mechanisms that govern
      inflammatory processes. Here, we present a combined experimental and
      computational approach to understanding the biochemical basis of eicosanoid
      metabolism in macrophages. Lipidomic and transcriptomic measurements and analyses
      reveal temporal and dynamic changes of the eicosanoid metabolic network in mouse
      bone marrow-derived macrophages (BMDM) upon stimulation of the Toll-like receptor
      4 with Kdo2-Lipid A (KLA) and stimulation of the P2X7 purinergic receptor with
      adenosine 5'-triphosphate. Kinetic models were developed for the cyclooxygenase
      (COX) and lipoxygenase branches of arachidonic acid metabolism, and then the rate
      constants were estimated with a data set from ATP-stimulated BMDM, using a two
      step matrix-based approach employing a constrained least-squares method followed
      by nonlinear optimization. The robustness of the model was validated through
      parametric sensitivity, uncertainty analysis, and predicting an independent
      dataset from KLA-primed ATP-stimulated BMDM by allowing the parameters to vary
      within the uncertainty range of the calculated parameters. We analyzed the
      functional coupling between COX isozymes and terminal enzymes by developing a
      PGH2-divided model. This provided evidence for the functional coupling between
      COX-2 and PGE2 synthase, between COX-1/COX-2 and PGD2 synthase, and also between
      COX-1 and thromboxane A2 synthase. Further, these functional couplings were
      experimentally validated using COX-1 and COX-2 selective inhibitors. The
      resulting fluxomics analysis demonstrates that the "multi-omics" systems biology
      approach can define the complex machinery of eicosanoid networks. 

PMID- 24560003
TI  - Electroglottographic study of seven semi-occluded exercises: LaxVox, straw, lip
      trill, tongue-trill, humming, hand-over-mouth, and tongue-trill combined with
      hand-over-mouth.
AB  - INTRODUCTION: Semi-occluded vocal tract exercises (SOVTE) are often used in voice
      clinics. SOVTE change the acoustic vocal tract impedance in relation to the
      glottis impedance, improving voice quality. However, differences among SOVTE,
      such as the number of vibration sources into the vocal tract, are often
      disregarded by clinicians. Some SOVTE present single, whereas others double
      source. This study aims at investigating changes in voice production pattern for
      a series of SOVTE. A combined exercise (tongue-trill coupled with hand-over
      mouth) was implemented to illustrate the effect of a secondary source of
      vibration in the vocal tract. METHOD: Twenty-three healthy volunteers performed a
      series of SOVTE: LaxVox, straw, lip-trill, tongue-trill, hand-over-mouth,
      humming, and tongue-trill combined with hand-over-mouth. Comfortable phonation
      served as control exercise. The dependent variables were electroglottography
      contact quotient (CQ), contact quotient range (CQr), fundamental frequency (F0),
      fundamental frequency range, and difference between the first formant frequency
      and F0 (F1 - F0). RESULTS: A significant difference for CQr scores compared with
      comfortable phonation was found for the combined tongue-trill with hand-over
      mouth, lip-trill, LaxVox, and tongue-trill exercises. The F1 - F0 acoustic
      analysis showed significant differences in scores for exercises with one versus
      two sources of vibration. DISCUSSION AND CONCLUSION: The results indicate that
      SOVTE should be divided into two groups, as follows: (a) steady (single sourced)
      with lower CQr and F1 - F0 difference (hand-over-mouth, humming, and straw) and
      (b) fluctuating (dual source) with larger CQr and F1 - F0 difference (tongue
      trill, lip-trill, and LaxVox). Because of these differences, also different
      therapeutic effects can be expected. Tongue-trill combined with hand-over-mouth
      exhibited mixed effects of both the exercise groups.

PMID- 24560002
TI  - The psychometric properties of the PABS-PT in neck pain patients: a validation
      study.
AB  - OBJECTIVE: This study aims to assess the reliability and validity of the Pain
      Attitudes and Beliefs Scale for Physiotherapists (PABS-PT) in neck pain patients.
      Three research goals were formulated. (1): to reexamine the factor structure of
      the PABS-PT, (2) to assess the test-retest reliability of the PABS-PT and (3) to
      determine the construct validity of the biomedical factor of the PABS-PT.
      METHODS: Manual therapists (n = 272) included in this study participated in an
      educational upgrade program for a professional masters' degree in the Netherlands
      and completed the Health Care Providers' Pain and Impairment Relationship Scale
      and the PABS-PT. Principal Axis Factor analysis was performed and correlation
      coefficients were calculated. In addition, Bland and Altman plots and the
      smallest real difference were determined. RESULTS: We performed factor analysis
      on 182 questionnaires and test-rest calculations on 73 questionnaires. The
      principal factor analysis confirmed the existing interpretable 2-factor model of
      a 'biomedical treatment orientation' and a 'behavioral treatment orientation'.
      Test-retest reliability was 'moderate' to 'good' and construct validity for the
      biomedical factor was 'moderate' to 'substantial'. CONCLUSION: The PABS-PT shows
      a consistent factor structure and good test-retest reliability and construct
      validity. More research is needed to gain further insight in the interplay
      between implicit and explicit attitudes and the dynamics of the PABS-PT score
      across different body parts.

PMID- 24560004
TI  - Cross-cultural adaptation, validation, and cutoff values of the Brazilian version
      of the Voice Symptom Scale-VoiSS.
AB  - OBJECTIVES: The present study sought to determine the validity, reliability, and
      responsiveness of the Brazilian Portuguese Voice Symptom Scale (VoiSS) and also
      identify characteristics of efficacy and cutoff values that discriminate
      dysphonic from vocally healthy individuals. STUDY DESIGN: Cross-sectional,
      nonrandomized, prospective study with controls. METHODS: Thirty hundred subjects
      (160 with dysphonia and 140 without dysphonia) completed the Brazilian version of
      the VoiSS as well as a vocal self-assessment scale using a five-point rating
      system (excellent, very good, good, fair, and poor). RESULTS: The Brazilian
      version of VoiSS, referred to as the Escala de Sintomas Vocais (ESV), was valid,
      reliable, and responsive. A score of 16 was determined to be highly sensitive
      (100%) and specific (100%) for individuals with dysphonia. CONCLUSIONS: The
      Brazilian version of VoiSS or ESV demonstrated a high degree of validity,
      reliability, and responsiveness with regard to differentiating aberrant vocal
      function and was valuable as an instrument to quantify the response to treatment
      in patients with dysphonia. The cutoff value that discriminates individuals with
      dysphonia from vocally healthy subjects was 16.

PMID- 24560006
TI  - A rare case of localised oral amyloid of the labial mucosa.
AB  - Amyloidosis is often a systemic process, and localised oral amyloidosis is rare.
      We present the case of a young woman with amyloid deposition in the labial mucosa
      of her lower lip. Systemic involvement was excluded by comprehensive assessment
      at the UK Amyloidosis Centre. Of 40 previously reported cases of localised oral
      amyloidosis we found only one that was limited to the labial mucosa. 

PMID- 24560005
TI  - Adolescent intermittent ethanol exposure diminishes anhedonia during ethanol
      withdrawal in adulthood.
AB  - Adolescent alcohol use may interfere with neurodevelopment, increasing the
      likelihood of adult alcohol use disorders (AUDs). We investigated whether
      adolescent intermittent ethanol (AIE) exposure alters the adult reward response
      to ethanol. Adolescent rats were administered ethanol once (moderate exposure;
      Cohort 1) or three times per day (severe exposure; Cohort 2) in a 2 days on/2
      days off pattern. In adulthood, subjects responded for electrical stimulation
      directed at the posterior lateral hypothalamus in a discrete-trial intracranial
      self-stimulation (ICSS) procedure that provides current-intensity thresholds as a
      measure of brain reward function. The effects of ethanol administration and
      withdrawal were assessed. Control rats showed dose-dependent threshold elevations
      after acute ethanol, indicating reward deficits. A majority of moderately AIE
      exposed rats (Cohort 1) showed threshold lowering after ethanol, suggesting
      ethanol-induced reward enhancement in this sub-set of rats. Rats exposed to
      severe AIE (Cohort 2) showed no threshold elevation or lowering, suggesting a
      blunted affective ethanol response. Daily ethanol induced threshold elevations
      24h after administration in control rats but not in either group of AIE-exposed
      rats, suggesting decreased sensitivity to the negative affective state of ethanol
      withdrawal. Withdrawal from a 4-day ethanol binge produced robust and enduring
      threshold elevations in all rats, although threshold elevations were diminished
      in rats exposed to severe AIE. These results indicate that AIE exposure
      diminished reward deficits associated with ethanol intoxication and withdrawal
      and may have increased ethanol-induced reward enhancement in a sub-set of rats.
      In humans, enhanced ethanol reward accompanied by reduced withdrawal severity may
      contribute to the development of AUDs. 

PMID- 24560008
TI  - Nonlinear dynamics of runaways among children and adolescents: disruptive
      disorder or step toward a suicide attempt?
AB  - The aim of this study is to analyze the decision-making process whereby
      susceptible adolescents end up choosing the option to run away or attempt
      suicide. Our basic hypothesis is that this transition is largely based on
      cooperative mechanisms. The runaway state is regarded as a potential precursor of
      the suicidal one. A mathematical model incorporating these processes is developed
      from which the time evolution and the values of the susceptible, runaway and
      suicidal populations are evaluated in terms of a number of key parameters. It is
      shown that for appropriate ranges of parameter values the interactions present in
      the system eventually end up counteracting both runaway and suicidal attempts.
      Quantitatively this is shown by the existence of stable solutions of the model
      equations in which the populations of both suicidal and runaway individuals end
      up being zero, although in some cases a significant temporary enhancement can
      take place. But as the parameters are varied beyond these ranges the system
      starts sustaining non-trivial stable states, in which the populations of
      suicidals or runaways are maintained at non-zero levels. This hints at prevention
      strategies and crisis management such as separation from the environment and
      specific treatment different from those dispending traditional adolescent
      psychiatric units.

PMID- 24560009
TI  - Dynamic patterns in psychotherapy--discontinuous changes and critical
      instabilities during the treatment of obsessive compulsive disorder.
AB  - In therapy processes of a variety of disorders, discontinuous trajectories of
      symptom changes have been identified. In this study, we are reporting on such
      'sudden gains' that occur in the treatment of clients with obsessive-compulsive
      disorder (OCD) following cognitive-behavioral group therapy. Time series analysis
      of data taken from 18 OCD clients revealed that a discontinuously shaped symptom
      reduction took place already before exposure/response prevention (ERP) in a large
      number of clients. Coincidently with the steepest gradient of symptom change an
      increased level of dynamic complexity in daily ratings of 47 items of a specific
      change questionnaire was observed. Our results support hypotheses from the theory
      of complex self-organizing systems, postulating nonstationarity and critical
      instabilities during order transitions. Our study underlines the usefulness of
      real-time monitoring procedures with high-frequency ratings (daily measurements)
      in therapeutic routine practice.

PMID- 24560010
TI  - Catastrophe model of the accident process, safety climate, and anxiety.
AB  - This study aimed (a) to address the evidence for situational specificity in the
      connection between safety climate to occupational accidents, (b) to resolve
      similar issues between anxiety and accidents, (c) to expand and develop the
      concept of safety climate to include a wider range of organizational constructs,
      (d) to assess a cusp catastrophe model for occupational accidents where safety
      climate and anxiety are treated as bifurcation variables, and environ-mental
      hazards are asymmetry variables. Bifurcation, or trigger variables can have a
      positive or negative effect on outcomes, depending on the levels of asymmetry, or
      background variables. The participants were 1262 production employees of two
      steel manufacturing facilities who completed a survey that measured safety
      management, anxiety, subjective danger, dysregulation, stressors and hazards.
      Nonlinear regression analyses showed, for this industry, that the accident
      process was explained by a cusp catastrophe model in which safety management and
      anxiety were bifurcation variables, and hazards, age and experience were
      asymmetry variables. The accuracy of the cusp model (R2 = .72) exceeded that of
      the next best log-linear model (R2 = .08) composed from the same survey
      variables. The results are thought to generalize to any industry where serious
      injuries could occur, although situationally specific effects should be
      anticipated as well.

PMID- 24560011
TI  - A mathematical model of 'Pride and Prejudice'.
AB  - A mathematical model is proposed for interpreting the love story between
      Elizabeth and Darcy portrayed by Jane Austen in the popular novel Pride and
      Prejudice. The analysis shows that the story is characterized by a sudden
      explosion of sentimental involvements, revealed by the existence of a saddle-node
      bifurcation in the model. The paper is interesting not only because it deals for
      the first time with catastrophic bifurcations in romantic relation-ships, but
      also because it enriches the list of examples in which love stories are described
      through ordinary differential equations.

PMID- 24560013
TI  - An automated alert system in a transitional care program to improve continuity of
      care in the emergency department: a strategy for reducing rehospitalizations.

PMID- 24560012
TI  - Phase II trial of mapatumumab, a fully human agonist monoclonal antibody to tumor
      necrosis factor-related apoptosis-inducing ligand receptor 1 (TRAIL-R1), in
      combination with paclitaxel and carboplatin in patients with advanced non-small
      cell lung cancer.
AB  - BACKGROUND: This phase II study examined the efficacy of mapatumumab in
      combination with paclitaxel and carboplatin in patients with non-small-cell lung
      cancer (NSCLC). PATIENTS AND METHODS: Patients with stage IIIB or stage IV
      advanced primary NSCLC were randomly assigned (1:1:1) to receive up to 6 courses
      of standard-dose paclitaxel and carboplatin or a combination of paclitaxel,
      carboplatin, and mapatumumab (10 mg/kg or 30 mg/kg). Primary efficacy end points
      were overall response rate and median progression-free survival (PFS). Secondary
      efficacy end points included disease control rate, overall survival (OS), time to
      response, and duration of response. Exploratory studies included evaluation of
      historical biopsy materials for TRAIL-R1 expression by immunohistochemical
      analysis and serum levels of M30, a marker of apoptosis, before and after the
      first 2 doses of mapatumumab. Safety parameters, including adverse events (AEs),
      laboratory tests, and immunogenicity, were assessed. RESULTS: The majority of
      patients had stage IV disease (79%) and an Eastern Cooperative Oncology Group
      (ECOG) performance status of 0 (58%); baseline characteristics were similar
      across treatment arms. No improvements in response or disease control rates, PFS,
      or OS were gained from the addition of mapatumumab. Adverse events in the
      mapatumumab arms were generally consistent with toxicities seen in the
      carboplatin and paclitaxel control arm. Levels of M30 were highly variable, and
      consistent patterns were not seen across treatment arms. CONCLUSION: This study
      showed no clinical benefit from adding mapatumumab to carboplatin and paclitaxel
      in unselected patients with NSCLC. The combination was generally well tolerated.
      The possibility of subgroups sensitive to mapatumumab is discussed.

PMID- 24560014
TI  - A case of delayed presentation of thigh compartment syndrome.
AB  - BACKGROUND: Thigh compartment syndrome is a rare and devastating process. It
      generally occurs within hours to days of a traumatic event, although cases have
      been reported nearly 2 weeks after the initial event. OBJECTIVES: To evaluate the
      literature describing the timing between inciting event and presentation of thigh
      compartment syndromes, with a focus on delayed presentations of this rare
      condition. To describe the unique properties of thigh compartments, and finally,
      to review the anatomy and techniques needed to measure the compartment pressures
      of the thigh. CASE REPORT: A case of a 54-year-old man is presented. He sustained
      trauma to his thigh 17 days prior to presenting to our ED with severe, sudden
      onset pain in his right thigh. Compartment pressures were measured and confirmed
      the diagnosis of compartment syndrome caused by two large intramuscular
      hematomas. No other contributing events were identified. CONCLUSIONS: Compartment
      syndrome in the thigh should be considered in patients with a concerning
      examination and a history of recent trauma. This particular case represents the
      longest reported time between injury and development of a thigh compartment
      syndrome.

PMID- 24560015
TI  - Acute gastric dilatation causing acute limb ischemia in an anorexia nervosa
      patient.
AB  - BACKGROUND: Acute gastric dilatation is a rare but severe complication of
      anorexia nervosa. Gastric dilatation causing abdominal compartment syndrome with
      lower-limb ischemia is even less common. This case report illustrates the
      importance of a holistic clinical approach of every patient presenting to the
      emergency department (ED), even when the reason for admittance is organ specific.
      CASE REPORT: We report the case of a young female patient presenting to the ED
      with a painful white left leg. Clinical examination revealed acute lower-limb
      ischemia, abdominal distention, and shock. Diagnostic work-up, including an
      abdominal computed tomography scan, showed compression of the aorta, inferior
      vena cava, and both iliac arteries, as well as hypoperfusion of the right kidney
      and left liver lobe, all due to compression by a massive gastric dilatation.
      Gastroscopy revealed a massively dilated stomach containing > 6 L of fluid and
      gastric wall ischemia. After decompression, the circulation to the lower limbs
      recovered immediately. The day after admission the patient developed an acute
      abdomen leading to a semi-urgent laparoscopy during which a sleeve gastrectomy
      was performed for the treatment of partial gastric necrosis. Clinical evolution
      afterward was favorable and the patient recovered completely. CONCLUSIONS: This
      case report underscores the importance of a thorough clinical examination in
      every patient admitted to the ED. Early diagnosis and treatment are mandatory in
      preventing fatal complications.

PMID- 24560016
TI  - Point-of-care ultrasound diagnosis of necrotizing fasciitis missed by computed
      tomography and magnetic resonance imaging.
AB  - BACKGROUND: Necrotizing fasciitis (NF) is a rare but deadly disease. Diagnosis of
      necrotizing soft tissue infections can be challenging for a variety of reasons.
      Point-of-care (POC) ultrasound (US) has been described as a diagnostic tool to
      help the acute care clinician make the early diagnosis that is imperative to
      optimize outcomes. OBJECTIVE: To report a case of Group A Streptococcus NF
      recognized with POC US, and subsequent negative findings on computed tomography
      (CT) and magnetic resonance imaging (MRI). CASE REPORT: A 54-year-old diabetic
      woman presented to the Emergency Department with atraumatic right foot and lower
      leg pain associated with fever. Examination was concerning for NF, and a POC US
      was performed, which showed thickened deep fascia and fluid tracking along the
      deep fascial plane, with fluid pockets measuring 6 mm in depth, consistent with
      NF. Surgical consultation was obtained. Per request, CT and MRI of the patient's
      lower extremity were performed; both were interpreted by the radiologist as
      showing changes consistent with cellulitis. Septic shock and multisystem organ
      failure ensued; the patient was eventually taken to the operating room, where
      operative findings were consistent with NF. Operative cultures grew Streptococcus
      pyogenes. CONCLUSION: NF is a surgical emergency. Early and accurate diagnosis is
      critical to ensure the necessary aggressive management needed to optimize
      outcomes. This case illustrates the utility of POC US to make the prompt
      diagnosis of NF, particularly in light of subsequently negative CT and MRI.

PMID- 24560017
TI  - The Hampton hump in acute pulmonary embolism.

PMID- 24560018
TI  - Ki-67 expression is increased in p16-expressing triple-negative breast carcinoma
      and correlates with p16 only in p53-negative tumors.
AB  - Increased Ki-67 expression is associated with worse prognosis in patients with
      triple-negative breast carcinoma (TNBC); Ki-67 is widely used as a prognostic
      marker for TNBC patients. p16 and p53 are tumor suppressors. The status of p53
      expression can divide TNBCs into 2 biologically distinct subgroups. The
      relationship of p16 expression with Ki-67 and its association with the status of
      p53 in TNBC patients have not been well characterized. In this study, we
      investigated p16 expression in 60 high-grade invasive TNBC cases and its
      relationship with Ki-67 in different groups of TNBCs and correlated p16 with Ki
      67 in p53-positive and p53-negative subgroups. The tumors were immunolabeled for
      p16, Ki-67, and p53. Tissue microarrays were constructed with each tumor and
      adjacent normal breast tissue. Of the 60 tumors, 45 (75%) were found to have p16
      expression. The triple-negative tumors had significantly higher p16 expression
      compared with paired normal ducts (P < .0001). Mean expression level of Ki-67 in
      p16-positive tumors was significantly higher than that in p16-negative tumors
      regardless of the status of p53 (P < .05). p16 expression positively correlated
      with Ki-67 (69.05% +/- 7.23%) in the 22 p53-negative tumors (r = 0.739; P <
      .001). However, no correlation was found between p16 and Ki-67 (77.2% +/- 3.83%)
      in the 38 p53-positive tumors (r = 0.157; P = .424). These findings suggest that
      p16 may play a role in the proliferation and aggressiveness of p53-negative TNBC
      and provide insights into the potential prognostic value of p16 as well as a
      better understanding of tumor biology related to the Rb/p16 pathway
      abnormalities. 

PMID- 24560019
TI  - Fundic gland polyps and proton pump inhibitors: an obvious link, or an open
      question?

PMID- 24560020
TI  - Effect of simulated transport stress on the rat small intestine: A morphological
      and gene expression study.
AB  - The present study investigated the effects of simulated transport stress on
      morphology and gene expression in the small intestine of laboratory rats. Sprague
      Dawley rats were subjected to 35 degrees C and 0.1*g on a constant temperature
      shaker for physiological, biochemical, morphological and microarray analysis
      before and after treatment. The treatment induced obvious stress responses with
      significant decreases in body weight (P<0.01), increases in rectal temperature,
      serum corticosterone (CORT), serum glucose (GLU), creatine kinase (CK) and
      lactate dehydrogenase (LDH) levels (P<0.01), as well as expression of Hsp27/70/90
      mRNA (P<0.05; P<0.01). The rat jejunum was severely damaged and apoptotic after
      mimicking transport stress, which may mainly be related to cell death, oxidation
      reduction and hormone imbalance determined by microarray analysis. The
      bioinformatics analysis from the present study would provide insight into the
      potential mechanisms underlying transport stress-induced injury in the rat small
      intestine. 

PMID- 24560021
TI  - Idiopathic burning mouth syndrome: a common treatment-refractory somatoform
      condition responsive to ECT.
AB  - Somatic symptom disorders are common causes of disability and suffering, and can
      pose significant management challenges. Idiopathic burning mouth syndrome is a
      challenging somatic symptom disorder with relatively high prevalence,
      particularly among post-menopausal women. Here, we present the case of a woman
      with severe treatment refractory idiopathic burning mouth syndrome and comorbid
      major depressive disorder, who was successfully treated with bitemporal
      electroconvulsive therapy. This case highlights the potential effectiveness of
      electroconvulsive therapy in idiopathic burning mouth syndrome when other
      treatment options have been exhausted. 

PMID- 24560022
TI  - Night-time experiences and daytime dissociation: a path analysis modeling study.
AB  - Dissociative symptoms may be the by-products of a labile sleep-wake cycle (Koffel
      and Watson, 2009a). This may help to explain why dissociation overlaps with
      fantasy proneness and cognitive failures. Using path analysis, we tested to what
      extent data gathered in a nonclinical, predominantly female sample (N=139)
      supported two conceptual models. The first model assumes that unusual sleep
      experiences increase fantasy proneness and cognitive failures, which in turn
      encourage trait dissociation and reports of trauma. The second model assumes that
      trauma leads to dissociative experiences both directly and through its influence
      on sleep. In this cross-sectional design, the data were reasonably well described
      by both models. Importantly, in both models, unusual sleep experiences serve as
      antecedents of trait dissociation. Our analysis underlines the importance of
      unusual sleep experiences and may inspire treatment intervention focusing on
      sleep normalization. 

PMID- 24560023
TI  - Introduction and commentary: paving the way for biosimilars in oncology, part 2:
      focus on safety and clinical trial considerations.

PMID- 24560024
TI  - Developing clinical trials for biosimilars.
AB  - Biosimilars offer the prospect of providing efficacious and safe treatment
      options for many diseases, including cancer, while potentially increasing
      accessibility with greater affordability relative to biologics. Because biologics
      are large, complex molecules that cannot be exactly duplicated, biosimilars
      cannot be considered "generic" versions of biologic drugs. This review will
      examine important considerations for biosimilar clinical trials. Since the aim of
      biosimilar manufacturing is to produce a molecule highly similar to the reference
      biologic, a comparability exercise is needed to demonstrate similarity with the
      reference biologic product based on physicochemical characterization. In vitro
      analytical studies and in vivo studies as well as pharmacokinetic/pharmacodynamic
      (PK/PD) assessments also are conducted. Lastly, because it may not be possible to
      fully characterize a biosimilar in relation to its reference biologic, robust
      pharmacovigilance strategies are utilized to ensure that any matters in regard to
      safety can be monitored. Other key topics will be discussed, including regulatory
      guidance for the evaluation of biosimilars, clinical trial design considerations,
      and whether data submitted for the approval of a biosimilar for one indication
      can be extrapolated to other indications for which the reference biologic is
      approved. European and Canadian experiences in biosimilar development will be
      reviewed. 

PMID- 24560026
TI  - Multidetector computed tomography of congenital aortic abnormalities.
AB  - For many years invasive angiographic techniques have been considered as the gold
      standard for the assessment of large arterial abnormalities. However, the
      complexities and complications inherent to invasive imaging have meant that more
      recently non-invasive techniques such as echocardiography, Magnetic Resonance
      Imaging (MRI) and multidetector CT (MDCT) have been increasingly used in
      congenital cardiovascular disorders. In particular, MDCT has emerged as a
      fundamental tool for the diagnosis and pre-surgical work-up of aortic
      abnormalities due to its high spatial resolution, large area of coverage, and
      short scan time, and therefore is now one of the most widely used modalities for
      the detection of congenital abnormalities of the aorta. The purpose of this
      pictorial review is to review the spectrum of abnormalities of the aorta than can
      be reliably detected by MDCT both in infants and in adulthood. Abnormalities of
      the aortic root, ascending aorta, aortic arch, and descending aorta will be
      described separately. 

PMID- 24560025
TI  - Biosimilar safety considerations in clinical practice.
AB  - Biologics are important treatments for a number of cancers. Patents for several
      biologics will expire over the next decade, removing a barrier to the development
      and commercialization of biosimilars. As biologics differ from small-molecule
      drugs due to their size and complexity, multifaceted manufacturing process, and
      their potential for immunogenicity, biosimilars cannot be considered "generic
      versions" of currently approved biologics. In highly regulated markets,
      biosimilars can be authorized only if they are demonstrated to be highly similar
      to the original drug from an analytical and clinical perspective. Any differences
      must be justified and shown to have no clinically meaningful effect on the safety
      and efficacy of the biosimilar. The European Medicines Agency has approved a
      number of biosimilars and the recent approval of the biosimilar infliximab
      monoclonal antibody is another regulatory milestone. This article will provide
      context regarding key safety issues addressed in biosimilar development,
      approval, and delivery, as well as inform oncologists on matters of safety to
      consider when prescribing biosimilars. Pertinent issues about safety from
      countries or regions where biosimilars are currently in use also will be
      reviewed. 

PMID- 24560027
TI  - Triptolide-containing formulation in patients with autosomal dominant polycystic
      kidney disease and proteinuria: an uncontrolled trial.

PMID- 24560028
TI  - External validation of the BIS (Berlin Initiative Study)-1 GFR estimating
      equation in the elderly.

PMID- 24560030
TI  - The 'other faunivory' revisited: Insectivory in human and non-human primates and
      the evolution of human diet.
AB  - The role of invertebrates in the evolution of human diet has been under-studied
      by comparison with vertebrates and plants. This persists despite substantial
      knowledge of the importance of the 'other faunivory', especially insect-eating,
      in the daily lives of non-human primates and traditional human societies,
      especially hunters and gatherers. Most primates concentrate on two phyla,
      Mollusca and Arthropoda, but of the latter's classes, insects (especially five
      orders: Coleoptera, Hymenoptera, Isoptera, Lepidoptera, Orthoptera) are
      paramount. An insect product, bees' honey, is particularly important, and its
      collection shows a reversal of the usual sexual division of labor. Human
      entomophagy involves advanced technology (fire, containers) and sometimes
      domestication. Insectivory provides comparable calorific and nutritional benefits
      to carnivory, but with different costs. Much insectivory in hominoids entails
      elementary technology used in extractive foraging, such as termite fishing by
      chimpanzees. Elucidating insectivory in the fossil and paleontological record is
      challenging, but at least nine avenues are available: remains, lithics, residues,
      DNA, coprolites, dental microwear, stable isotopes, osteology, and depictions.
      All are in play, but some have been more successful so far than others.

PMID- 24560029
TI  - The MultiTEP platform-based Alzheimer's disease epitope vaccine activates a broad
      repertoire of T helper cells in nonhuman primates.
AB  - BACKGROUND: As a prelude to clinical trials we have characterized B- and T-cell
      immune responses in macaques to AD vaccine candidates: AV-1955 and its slightly
      modified version, AV-1959 (with 3 additional promiscuous Th epitopes). METHODS: T
      and B-cell epitope mapping was performed using the ELISPOT assay and competition
      ELISA, respectively. RESULTS: AV-1955 and AV-1959 did not stimulate potentially
      harmful autoreactive T cells, but instead activated a broad but individualized
      repertoire of Th cells specific to the MultiTEP platform in macaques. Although
      both vaccines induced robust anti-Abeta antibody responses without producing
      antibodies specific to Th epitopes of MultiTEP platforms, analyses of cellular
      immune responses in macaques demonstrated that the addition of Th epitopes in the
      case of AV-1959 created a more potent, superior vaccine. CONCLUSION: AV-1959 is a
      promising vaccine candidate capable of producing therapeutically potent anti
      amyloid antibody in a broader population of vaccinated subjects with high MHC
      class II gene polymorphisms.

PMID- 24560032
TI  - Youth injury on farms: a complex problem.

PMID- 24560031
TI  - Helfrich model of membrane bending: from Gibbs theory of liquid interfaces to
      membranes as thick anisotropic elastic layers.
AB  - Helfrich model of membrane bending elasticity has been most influential in
      establishment and development of Soft-Matter Physics of lipid bilayers and
      biological membranes. Recently, Helfrich theory has been extensively used in Cell
      Biology to understand the phenomena of shaping, fusion and fission of cellular
      membranes. The general background of Helfrich theory on the one hand, and the
      ways of specifying the model parameters on the other, are important for
      quantitative treatment of particular biologically relevant membrane phenomena.
      Here we present the origin of Helfrich model within the context of the general
      Gibbs theory of capillary interfaces, and review the strategies of computing the
      membrane elastic moduli based on considering a lipid monolayer as a three
      dimensional thick layer characterized by trans-monolayer profiles of elastic
      parameters. We present the results of original computations of these profiles by
      a state-of-the-art numerical approach. 

PMID- 24560033
TI  - Youth suicide: new angles on an old problem.

PMID- 24560034
TI  - Understanding concussion reporting using a model based on the theory of planned
      behavior.
AB  - PURPOSE: Athlete's report of concussion symptoms to coaching or medical personnel
      is an important component of concussion risk reduction. This study applies a
      model based on the Theory of Planned Behavior (TPB) to the prediction of
      concussive symptom underreporting among late adolescent and young adult male ice
      hockey players. METHODS: Participants were members of an American Tier III Junior
      A ice hockey league (ages 18-21 years; male; n = 256). Twelve of 14 league teams
      and 97% of players within these teams agreed to participate. Written survey items
      assessed symptom reporting behavior, intention, perceived norms, self-efficacy,
      perceived outcomes of reporting, and concussion knowledge. Structural equation
      modeling was used to assess the significance of relationships hypothesized by the
      TPB-based model and the overall model fit. Data were collected in January 2013.
      RESULTS: Results supported the fit of the TPB-based model in explaining reporting
      behavior; all model pathways were significant in the hypothesized direction. Of
      the perceived reporting outcomes assessed, those related to athletic performance
      were identified as most strongly associated with reporting intention.
      CONCLUSIONS: Results of this study suggest the importance of considering factors
      such as perceived outcomes of reporting, perceived norms, and self-efficacy, in
      addition to knowledge, when analyzing concussion underreporting among adolescent
      athletes. As concussion education for athletes becomes increasingly mandated,
      testing and applying psychosocial theories such as TPB may help increase program
      efficacy.

PMID- 24560036
TI  - School-located vaccination of adolescents with insurance billing: cost,
      reimbursement, and vaccination outcomes.
AB  - PURPOSE: To assess, in a school-located adolescent vaccination program that
      billed health insurance, the program costs, the proportion of costs reimbursed,
      and the likelihood of vaccination. METHODS: During the 2010-2011 school year,
      vaccination clinics were held for sixth- to eighth-grade students at seven Denver
      public schools. Vaccine administration and purchase costs were compared with
      reimbursement by insurers. Multivariate analyses were used to compare the
      likelihood of vaccination among students in intervention schools with students in
      control schools who did not participate in the program, with analyses stratified
      by grade (sixth grade vs. seventh-eighth grades). RESULTS: Fifteen percent (466
      of 3,144) of students attending intervention schools were vaccinated at school
      located vaccination clinics. Among students vaccinated at school, 41% were
      uninsured, 37% publicly insured, and 22% privately insured. Estimated vaccine
      administration costs were $23.98 per vaccine dose. Seventy-eight percent of
      vaccine purchase costs and 14% of vaccine administration costs were reimbursed by
      insurers; 41% of total program costs were reimbursed. Sixth-grade students in
      intervention schools were more likely than those in control schools to receive
      tetanus-diphtheria-acellular pertussis (risk ratio [RR], 1.30; 95% confidence
      interval [CI], 1.08, 1.57), meningococcal conjugate (RR, 1.42; CI, 1.18, 1.70),
      and human papillomavirus (for females only, RR, 1.69; CI, 1.21, 2.36) vaccines
      during the 2010-2011 school year, with similar results for seventh- to eighth
      grade students. CONCLUSIONS: Although school-located adolescent vaccination with
      billing appears feasible and likely to improve vaccination rates, improvements in
      insurance coverage and reimbursement rates may be needed for the long-term
      financial sustainability of such programs.

PMID- 24560035
TI  - The influence of deductible health plans on receipt of the human papillomavirus
      vaccine series.
AB  - PURPOSE: To evaluate whether enrollment in deductible health plans (DHP) with
      higher patient cost-sharing requirements than traditional health maintenance
      organization plans (HMP) decreased initiation and completion of the human
      papillomavirus (HPV) vaccine series recommended for prevention of cervical
      cancer. METHODS: This was a retrospective observational study of 9- to 26-year
      old females at Kaiser Permanente Georgia and Kaiser Permanente Colorado who were
      HPV vaccine naive at time of enrollment in a self-pay DHP or HMP in 2007.
      Estimates of rates of initiation and completion of the HPV vaccine series from
      plan enrollment in 2007 through December 2009 were obtained using Cox
      proportional hazards regressions (accounting for censoring) on samples matched on
      the propensity to enroll in a DHP versus HMP. RESULTS: Initiation of the HPV
      vaccine series was 22.2% and 24.4% in the DHP and HMP groups, respectively, at
      Kaiser Permanente Georgia; completion was 12.3% and 14.4% in the DHP and HMP
      groups, respectively. Human papillomavirus vaccine series initiation was higher
      at Kaiser Permanente Colorado, but completion was lower. In the Cox proportional
      hazards regressions, rates of initiation and completion of the HPV vaccine series
      did not differ significantly (p <= .05) by plan type (DHP vs. HMP) at both sites.
      The primary care visit rate included in these regressions had a significant,
      positive association with initiation and completion of the HPV vaccine series.
      CONCLUSIONS: Enrollment in a DHP versus an HMP did not directly affect initiation
      or completion of the HPV vaccine series among age-eligible females. Independent
      of plan type, more frequent primary care visits increased initiation and
      completion rates.

PMID- 24560037
TI  - Emergency department utilization among American Indian adolescents who made a
      suicide attempt: a screening opportunity.
AB  - PURPOSE: Reservation-based American Indian adolescents are at significant risk
      for suicide. Preventive approaches have not focused on medical service
      utilization patterns on reservations, which are typically limited to one local
      emergency department (ED). Patterns of ED utilization before suicide attempts
      were evaluated to identify opportunities for screening and intervention. METHODS:
      Cross-sectional study of Apache adolescents (aged 13-19 years) who attempted
      suicide and consented to medical chart review. Lifetime presenting problems for
      Indian Health Service ED visits before the index suicide attempt were extracted
      and coded. RESULTS: A total of 1,424 ED visits from 72 Apache adolescents were
      extracted (median lifetime visits, n = 18). In the year before the attempt, 82%
      (n = 59) of participants had had an ED visit for any reason and 26% (n = 19) for
      a psychiatric reason, including suicidal thoughts or self-harm. CONCLUSIONS:
      Service utilization data suggest that EDs are critical locations for reservation
      based suicide prevention. Suicide screening for all ED patients could increase
      early identification and treatment of this at-risk group.

PMID- 24560038
TI  - Determinants of weight loss dieting among adolescents: a longitudinal analysis.
AB  - PURPOSE: To prospectively assess characteristics associated with dieting
      behaviors in adolescence. METHODS: We analyzed 1,640 adolescents evaluated at 13
      and 17 years old (EPITeen cohort), Porto, Portugal. Dieting was assessed only at
      17 years, as self-reported frequency of dieting to lose weight in the previous 12
      months. The association between participants' characteristics and dieting was
      summarized using multinomial logistic regression for girls and binary logistic
      regression for boys. RESULTS: Dieting at 17 years old was significantly more
      prevalent in girls than in boys (respectively 27.6% and 10.5% for occasional
      dieting and 12.2% and 2.6% for frequent dieting). In both sexes, overweight and
      obese adolescents were significantly more likely to engage in dieting but body
      dissatisfaction was the strongest determinant among girls. Furthermore, dieting
      frequency also increased with depressive symptomatology and among those involved
      in health compromising behaviors. CONCLUSIONS: Besides body mass index, body
      image concerns and depressive symptomatology predict dieting throughout
      adolescence.

PMID- 24560039
TI  - Subcellular localization and responses of superoxide dismutase isoforms in local
      wheat varieties subjected to continuous soil drought.
AB  - Water is a key factor influencing the yield and quality of crops. One of the
      parameters of plant biological tolerance to constantly changing environmental
      conditions is the change of activities and numerous molecular forms of
      antioxidant enzymes. Two durum (Triticum durum Desf.) wheat varieties contrasting
      for drought tolerance, such as Barakatli-95 (drought tolerant) and Garagylchyg-2
      (drought sensitive) were grown over a wide area in the field. Experiments were
      carried out to study the effect of soil drought on changes in activities and
      subcellular localization of superoxide dismutase isoforms. The levels of
      malondialdehyde, glycine betaine and total proteins were also analyzed. The level
      of the enzyme activity appeared to depend on the wheat varieties, duration of
      drought and stages of leaf development. Native polyacrylamide gel electrophoresis
      (PAGE) revealed the presence of 9 isoenzymes of superoxide dismutase in wheat
      leaves during drought. Mn-SOD was found in the mitochondrial fractions, Fe-SOD in
      the chloroplast fraction and Cu/Zn-SOD is localized in all subcellular fractions.
      Wheat leaves contain three different isoforms of SOD (Mn-, Fe-, Cu/Zn-SOD). Three
      isoforms of Mn-SOD, one isoform of Fe-SOD and five of Cu/Zn-SOD were observed in
      wheat leaves using 3 mM KCN and 5 mM H2O2 as selective inhibitors. The expression
      of Mn-SOD was preferentially enhanced by drought stress. It seems that Mn-SOD
      isoforms more than SOD ones play a major role in the scavenging of superoxide
      radicals. The observed data showed that status of antioxidant enzymes such as SOD
      could provide a meaningful tool for depicting drought tolerance of wheat
      genotype. 

PMID- 24560040
TI  - [Conservative calibration of a clearance monitor system for waste material from
      nuclear medicine].
AB  - Clearance monitor systems are used for gross gamma measurements of waste
      potentially contaminated with radioactivity. These measurements are to make sure
      that legal requirements, e.g. clearance criteria according to the german
      radiation protection ordinance, are met. This means that measurement results may
      overestimate, but must not underestimate the true values. This paper describes a
      pragmatic way using a calibrated Cs-137 point source to generate a conservative
      calibration for the clearance monitor system used in the Medizinische Hochschule
      Hannover (MHH). The most important nuclides used in nuclear medicine are
      considered. The measurement result reliably overestimates the true value of the
      activity present in the waste. The calibration is compliant with the demands for
      conservativity and traceability to national standards. 

PMID- 24560041
TI  - Cancer in the elderly: is it time for palliative care in geriatric oncology?
AB  - BACKGROUND: Persons aged 65 and over are the fastest growing segment of the
      population in most Western countries. Although cancer-related death occurs far
      more commonly in older people than in any age group, studies on palliative care
      in older adults are lacking. OBJECTIVE: This paper aims at evaluating the needs
      in elderly patients affected by cancer and the state of the art of the research
      in palliative care in this setting. MATERIALS AND METHODS: A literature search
      was performed (PubMed) to identify relevant studies. Papers were reviewed for
      relevance to palliative care in the elderly. RESULTS: Elderly who need palliative
      care are frequently disregarded as individuals and may experience discrimination
      because of their age. Palliative care for older patients relates particularly to
      multiple treatments for various conditions. This causes extra complexities for
      the researchers. CONCLUSIONS: The aim of the study was not fully achieved due to
      the paucity of literature focusing upon these issues. The areas of investigation
      that need to be addressed comprise: establishing the prevailing symptoms in
      elderly patients, understanding patients' psychological/spiritual well-being and
      quality of life and elucidating the sources of caregiver burden, adapting
      research methodologies specifically for palliative care and comparing the needs
      and the outcomes of this age group to younger patients.

PMID- 24560042
TI  - Statins for millions more?

PMID- 24560043
TI  - Mental health in the UK: a work in progress.

PMID- 24560044
TI  - Health in austerity: hard decisions for hard times.

PMID- 24560045
TI  - Self-requested euthanasia for children in Belgium.

PMID- 24560048
TI  - Maternal and child mortality in Greece.

PMID- 24560047
TI  - Sulafa Ali: a pioneer of paediatric cardiology in Sudan.

PMID- 24560049
TI  - Mortality and the economic crisis in Greece.

PMID- 24560050
TI  - Greece's birth rates and the economic crisis.

PMID- 24560051
TI  - HIV surveillance and injecting drug users in Greece.

PMID- 24560052
TI  - HIV surveillance and injecting drug users in Greece.

PMID- 24560053
TI  - Redefining global health-care delivery.

PMID- 24560054
TI  - Redefining global health-care delivery.

PMID- 24560055
TI  - Wiping versus suction to clear neonatal airways at birth - Authors' reply.

PMID- 24560056
TI  - Wiping versus suction to clear neonatal airways at birth.

PMID- 24560057
TI  - Medecine de la Personne and the lost morality of the NHS in England.

PMID- 24560058
TI  - Greece's health crisis: from austerity to denialism.
AB  - Greece's economic crisis has deepened since it was bailed out by the
      international community in 2010. The country underwent the sixth consecutive year
      of economic contraction in 2013, with its economy shrinking by 20% between 2008
      and 2012, and anaemic or no growth projected for 2014. Unemployment has more than
      tripled, from 7.7% in 2008 to 24.3% in 2012, and long-term unemployment reached
      14.4%. We review the background to the crisis, assess how austerity measures have
      affected the health of the Greek population and their access to public health
      services, and examine the political response to the mounting evidence of a Greek
      public health tragedy. 

PMID- 24560059
TI  - Sudden, severe headache: an unexpected culprit.

PMID- 24560060
TI  - [An update of the obstetrics hemorrhage treatment protocol].
AB  - Obstetric hemorrhage is still a major cause of maternal and fetal morbimortality
      in developed countries. This is an underestimated problem, which usually appears
      unpredictably. A high proportion of the morbidity of obstetric hemorrhage is
      considered to be preventable if adequately managed. The major international
      clinical guidelines recommend producing consensus management protocols, adapted
      to local characteristics and keep them updated in the light of experience and new
      scientific publications. We present a protocol updated, according to the latest
      recommendations, and our own experience, in order to be used as a basis for those
      anesthesiologists who wish to use and adapt it locally to their daily work. This
      last aspect is very important to be effective, and is a task to be performed at
      each center, according to the availability of resources, personnel and
      architectural features. 

PMID- 24560061
TI  - Influence of different systems for feeding supplements to grazing dairy cows on
      milk fatty acid composition.
AB  - This study investigated the effects of different strategies for feeding
      supplements to grazing dairy cows on the proportions of fatty acids in milk. Two
      hundred and sixteen cows were fed supplementary grain and forage according to one
      of 3 different strategies; (1) CONTROL: cows grazed perennial ryegrass pasture
      (14 kg dry matter/d) supplemented with milled barley grain fed in the milking
      parlour and pasture silage offered in the paddock; (2) Partial mixed ration 1
      (PMR1): same pasture allotment and supplement as CONTROL strategy, but the
      supplements presented as a mixed ration after each milking in feedpad, and; (3)
      Partial mixed ration 2 (PMR2): same pasture allotment, supplemented with a mixed
      ration of milled barley grain, alfalfa hay, corn silage and crushed corn grain
      fed in a feedpad. Within each strategy, cows were assigned to receive either 6,
      8, 10 or 12 kg dry matter supplement/cow per d. Milk fatty acid proportions from
      cows fed CONTROL and PMR1 strategies were similar and different from those fed
      PMR2, particularly at 10 to 12 kg dry matter supplement/cow per d. The reduction
      in milk fat yield and concentration in cows fed high amounts of supplement as
      CONTROL and PMR1 was coincident with 4 * increase in 10t-18:1 proportion. The
      composition of the partial mixed ration (PMR) and the amount offered affected
      milk fatty acid proportions and milk fat content, however, the method of
      supplementation did not. 

PMID- 24560062
TI  - Cost-effectiveness of ranolazine added to standard-of-care treatment in patients
      with chronic stable angina pectoris.
AB  - Ranolazine has been shown to decrease angina pectoris frequency and nitroglycerin
      consumption. We assessed the cost-effectiveness of ranolazine when added to
      standard-of-care (SoC) antianginals compared with SoC alone in patients with
      stable coronary disease experiencing >=3 attacks/week. A Markov model utilizing a
      societal perspective, a 1-month cycle length, and a 1-year time horizon was
      developed to estimate costs (2013 US$) and quality-adjusted life years (QALYs)
      for patients receiving and not receiving ranolazine. Patients entered the model
      in 1 of the 4 angina frequency health states based upon Seattle Angina
      Questionnaire angina frequency (SAQAF) scores (100=no; 61 to 99=monthly; 31 to
      60=weekly; and 0 to 30=daily angina) and were allowed to transition between
      states or to death based upon probabilities derived from the Efficacy of
      Ranolazine in Chronic Angina and other studies. Patients not responding to
      ranolazine in month 1 (not improving >=1 SAQAF health state) were assumed to
      discontinue ranolazine and behave like SoC patients. Ranolazine patients lived a
      mean of 0.700 QALYs at a cost of $15,661. Those not receiving ranolazine lived
      0.659 QALYs and at a cost of $14,321. The incremental cost-effectiveness ratio
      (ICER) for the addition of ranolazine was $32,682/QALY. The ICER was most
      sensitive to ranolazine cost but only exceeded $50,000/QALY when the cost of
      ranolazine increased >32% above base case. The ICER remained <$50,000/QALY when
      indirect costs were excluded, and mortality rates were assumed equivalent between
      SAQAF health states. Monte Carlo simulation found ranolazine cost-effective in
      97% of 10,000 iterations at a $50,000/QALY willingness-to-pay threshold. In
      conclusion, ranolazine added to SoC is cost-effective in patients with weekly or
      daily angina.

PMID- 24560063
TI  - Usefulness of the SYNTAX score to predict acute kidney injury after percutaneous
      coronary intervention (from the Acute Catheterization and Urgent Intervention
      Triage Strategy Trial).
AB  - The synergy between percutaneous coronary intervention (PCI) with Taxus and
      cardiac surgery (SYNTAX) score (SS) has prognostic utility for ischemic outcomes
      in patients undergoing PCI. Acute kidney injury (AKI) after PCI has been
      demonstrated to be associated with adverse outcomes. However, the relation
      between the SS and AKI after PCI has yet to be fully investigated. We therefore
      sought to study this relation in the formal angiographic substudy of the large
      Acute Catheterization and Urgent Intervention Triage Strategy trial. We
      stratified 2,268 patients who underwent PCI for non-ST-segment elevation acute
      coronary syndromes by postprocedural AKI status and by SS tertiles (SS<7, 7 to
      12, and >12). We also assessed rates of in-hospital, 30-day, and 1-year adverse
      outcomes. A total of 226 patients (10%) developed AKI, and rates in the highest
      Acute Catheterization and Urgent Intervention Triage Strategy SS tertile (>12)
      were significantly greater than those in the intermediate (7 to 12) and lowest
      tertiles (<7; 13% vs 8.9% vs 7.7%, respectively, p=0.002). By multivariable
      analysis, the SS was independently associated with AKI (odds ratio per 10 SS
      points 1.22, 95% confidence interval 1.04 to 1.43, p=0.02. Rates of major adverse
      cardiovascular events and net adverse clinical events increased significantly by
      SS tertile and were more common in patients who developed AKI. Patients who
      developed AKI experienced higher in-hospital, 30-day, and 1-year rates of
      mortality. In this large study, the SS was independently associated with AKI
      after PCI for non-ST-segment elevation acute coronary syndromes, and patients who
      developed AKI experienced worse short-term and long-term outcomes.

PMID- 24560064
TI  - Predictors of moderate-to-severe pericardial effusion, cardiac tamponade, and
      electromechanical dissociation in patients with ST-elevation myocardial
      infarction.
AB  - Occurrence of moderate-to-severe pericardial effusion (PE; >=10 mm), cardiac
      tamponade (CT), and sudden electromechanical dissociation (EMD) was investigated
      in 4,361 patients with ST-elevation myocardial infarction from 1993 to 2011 in 3
      different periods: 1993 to 2000 (n: 1,488); 2001 to 2008 (n: 1,844); and 2009 to
      2011 (n: 1,014). Their predictors, including the use of no reperfusion therapy
      (n: 1,186), thrombolysis (n: 1,607), or primary percutaneous coronary
      intervention (PPCI, n: 1,562), were also evaluated. Incidence of PE (8.7%, 6.8%,
      and 5.0%), CT (5.0%, 2.9%, and 1.9%), and EMD (3.7%, 1.7%, and 1.0%), declined
      over the 3 periods as did mortality (12.0% 8.2%, and 5.9%) with different rates
      of thrombolytic therapy (52%, 37%, and 14%) and PPCI (7%, 38%, and 76%; all
      p<0.001). In patients treated without reperfusion therapy, thrombolysis, and
      PPCI, incidence of PE (12.0%, 5.7%, and 4.3%), CT (6.0%, 3.0%, and 2.2%), and EMD
      (4.1%, 2.2%, and 0.8%) was different as was mortality (14.4%, 8.3%, and 5.9%; all
      p<0.001). Independent predictors of PE were lateral infarction (odds ratio [OR]
      4.09, 95% confidence interval [CI] 2.57 to 6.49), increasing age (OR 1.05, 95% CI
      1.04 to 1.07), number of electrocardiographic leads involved (OR 1.34, 95% CI
      1.23 to 1.45), and admission delay (OR 1.01, 95% CI 1.01 to 1.02). Increasing
      ejection fraction (OR 0.97, 95% CI 0.96 to 0.98), thrombolysis (OR 0.53, 95% CI
      0.37 to 0.75), and PPCI (OR 0.35, 95% CI 0.25 to 0.50), however, were protectors
      (all p<0.001). Lateral infarction, age, number of leads involved, ejection
      fraction, thrombolytic therapy, and PPCI were also predictors/protectors of CT
      and EMD. In conclusion, PE, CT, and EMD rates in patients with ST-elevation
      myocardial infarction have objectively fallen in the last 2 decades, and their
      predictors are lateral site, increasing age, number of leads involved, and lack
      of reperfusion therapy. Late hospital admission is also a relevant predictor of
      PE.

PMID- 24560065
TI  - Relation of serum potassium level to long-term outcomes in patients with acute
      myocardial infarction.
AB  - Potassium plays a key role in normal myocardial function, and current guidelines
      recommend that serum potassium levels be maintained from 4.0 to 5.0 mEq/L in
      patients with acute myocardial infarction (AMI). However, the impact of serum
      potassium levels on long-term mortality has not been evaluated. We
      retrospectively studied 1,924 patients diagnosed with AMI. The average serum
      potassium levels measured throughout the hospitalization were obtained and
      statistically analyzed. Patients were categorized into 5 groups to determine the
      relation between mean serum potassium and long-term mortality: <3.5, 3.5 to <4.0,
      4.0 to <4.5, 4.5 to <5.0, and >=5 mEq/L. The long-term mortality was lowest in
      the group of patients with potassium levels of 3.5 to <4.0 mEq/L, whereas
      mortality was higher in the patients with potassium levels>=4.5 or <3.5 mEq/L. In
      a multivariate Cox-proportional regression analysis, the mortality risk was
      greater for serum potassium levels of >4.5 mEq/L (hazard ratio [HR] 1.71, 95%
      confidence interval [CI] 1.04 to 2.81 and HR 4.78, 95% CI 2.14 to 10.69, for
      patients with potassium levels of 4.5 to <5.0 mEq/L and >=5.0, respectively)
      compared with patients with potassium levels of 3.5 to <4.0 mEq/L. The mortality
      risk was also higher for patients with potassium levels<3.5 mEq/L (HR 1.55, 95%
      CI 0.94 to 2.56). In contrast to the association with long-term mortality, there
      was no relation between serum potassium levels and the occurrence of ventricular
      arrhythmias. The results of the current analysis suggest that there is a need for
      change in our current concepts of the ideal serum potassium levels in patients
      with AMI.

PMID- 24560066
TI  - Comparison of lipid management in patients with coronary versus peripheral
      arterial disease.
AB  - Peripheral arterial disease (PAD), similar to coronary artery disease (CAD), is a
      significant predictor of cardiovascular morbidity and mortality. Guidelines
      recommend a low-density lipoprotein (LDL) goal of <100 mg/dl for both groups. We
      assessed whether lipid control and statin use were as aggressively applied to PAD
      as to patients with CAD. This retrospective study of patients with the diagnosis
      of CAD, PAD, or both CAD and PAD compared lipid levels and statin use. For
      comparison of statins, we used a statin potency unit (1 potency unit=10 mg of
      simvastatin). Among 11,134 subjects (CAD 9,563, PAD 596, and both CAD and PAD
      975), mean LDL in the PAD group was higher than the CAD (92 vs 83 mg/dl,
      respectively, p<0.001) and the combined CAD and PAD groups (92 vs 80 mg/dl,
      respectively, p<0.001). Fewer patients with PAD achieved a target LDL of <100
      mg/dl compared with CAD (62% vs 78%, respectively, p<0.001) and the combined
      group (62% vs 79%, respectively, p<0.001). Similar differences were noted for a
      target LDL of <70 mg/dl. Compared with the CAD group, a lesser number of patients
      with PAD received statin therapy (76% vs 100%, respectively, p<0.001) with lower
      mean potency unit (5.3 vs 8.1, respectively, p<0.001). In conclusion, our study
      demonstrated lower use and less aggressive application of statins in patients
      with PAD compared with patients with CAD, ensuing lower mean LDL in the CAD and
      combined PAD and CAD groups. Our study suggests that physicians are more
      aggressive with lipid control in patients with CAD compared with patients with
      PAD alone.

PMID- 24560068
TI  - The Teen Pregnancy Prevention Program: an evidence-based public health program
      model.

PMID- 24560067
TI  - A systematic review of the literature on self-management interventions and
      discussion of their potential relevance for people living with HIV in sub-Saharan
      Africa.
AB  - OBJECTIVE: This study systematically reviews the literature on self-management
      interventions provided by health care teams, community partners, patients and
      families and discusses the potential relevance of these interventions for people
      living with HIV in sub-Saharan Africa. METHODS: We searched major databases for
      literature published between 1995 and 2012. 52 studies were included in this
      review. RESULTS: The review found very few studies covering people living with
      HIV and generally inconclusive evidence to inform the development of chronic care
      policy and practice in sub-Saharan Africa. CONCLUSION: Chronic care models and
      self-management interventions for sub-Saharan Africa has not been a research
      priority. Furthermore, the results question the applicability of these models and
      interventions in sub-Saharan Africa. There is a need for studies to fill this gap
      in view of the rapidly increasing number of people needing chronic care services
      in Africa. PRACTICE IMPLICATIONS: The established practices for long-term support
      for HIV patients are still the most valid basis for promoting self-management.
      This will be the case until there are more studies which assess those practices
      and their effect on self-management outcomes and other studies which assess the
      utility and feasibility of applying chronic care models that have been developed
      in high-income countries.

PMID- 24560069
TI  - Practical experience from the Office of Adolescent Health's large scale
      implementation of an evidence-based Teen Pregnancy Prevention Program.
AB  - After 3 years of experience overseeing the implementation and evaluation of
      evidence-based teen pregnancy prevention programs in a diversity of populations
      and settings across the country, the Office of Adolescent Health (OAH) has
      learned numerous lessons through practical application and new experiences. These
      lessons and experiences are applicable to those working to implement evidence
      based programs on a large scale. The lessons described in this paper focus on
      what it means for a program to be implementation ready, the role of the program
      developer in replicating evidence-based programs, the importance of a planning
      period to ensure quality implementation, the need to define and measure fidelity,
      and the conditions necessary to support rigorous grantee-level evaluation.

PMID- 24560070
TI  - From mission to measures: performance measure development for a Teen Pregnancy
      Prevention Program.
AB  - The Office of Adolescent Health (OAH) sought to create a comprehensive set of
      performance measures to capture the performance of the Teen Pregnancy Prevention
      (TPP) program. This performance measurement system needed to provide measures
      that could be used internally (by both OAH and the TPP grantees) for management
      and program improvement as well as externally to communicate the program's
      progress to other interested stakeholders and Congress. This article describes
      the selected measures and outlines the considerations behind the TPP measurement
      development process. Issues faced, challenges encountered, and lessons learned
      have broad applicability for other federal agencies and, specifically, for TPP
      programs interested in assessing their own performance and progress. 

PMID- 24560071
TI  - Office of Adolescent Health medical accuracy review process--helping ensure the
      medical accuracy of Teen Pregnancy Prevention Program materials.
AB  - The Office of Adolescent Health (OAH) developed a systematic approach to review
      for medical accuracy the educational materials proposed for use in Teen Pregnancy
      Prevention (TPP) programs. This process is also used by the Administration on
      Children, Youth, and Families (ACYF) for review of materials used in the Personal
      Responsibility Education Innovative Strategies (PREIS) Program. This article
      describes the review process, explaining the methodology, the team implementing
      the reviews, and the process for distributing review findings and implementing
      changes. Provided also is the definition of "medically accurate and complete" as
      used in the programs, and a description of what constitutes "complete"
      information when discussing sexually transmitted infections and birth control
      methods. The article is of interest to program providers, curriculum developers
      and purveyors, and those who are interested in providing medically accurate and
      complete information to adolescents. 

PMID- 24560072
TI  - Improving the replication success of evidence-based interventions: why a
      preimplementation phase matters.
AB  - PURPOSE: Careful scrutiny of the literature reveals that the preimplementation
      phase is often overlooked by researchers interested in understanding the
      portability of evidence-based interventions to other settings. In this paper we
      document the importance of preimplementation and the planning year in enabling
      adopters to identify and resolve potential implementation barriers. METHODS:
      Roger's diffusion of innovation theory and tenets of technology transfer models
      are the heuristic frameworks used to guide the analysis of the preimplementation
      phase of an abstinence replication study. RESULTS: The planning year allowed for
      the securing and consolidation of stakeholder support; preparing the organization
      for implementation; redressing issues with the intervention packet; responding to
      the cultural norms of the adopting community; fine tuning the training approach
      and addressing emergent challenges. CONCLUSIONS: Preimplementation provides
      adopters with opportunities to test the intervention before full implementation;
      and to identify and address potential threats to successful adoption.

PMID- 24560073
TI  - Using data to improve fidelity when implementing evidence-based programs.
AB  - In fall 2011, the South Carolina Campaign to Prevent Teen Pregnancy (SC
      Campaign), with funding from Office of Adolescent Health, began replicating an
      evidence-based curriculum, It's Your Game, Keep It Real in 12 middle schools
      across South Carolina. Fidelity of the curriculum was monitored by the use of
      lesson fidelity logs completed by curriculum facilitators and lesson observation
      logs submitted by independent classroom observers. These data were monitored
      weekly to identify possible threats to fidelity. The innovative model Fidelity
      Through Informed Technical Assistance and Training was developed by SC Campaign
      to react to possible fidelity threats in real time, through a variety of
      technical assistance modalities. Fidelity Through Informed Technical Assistance
      and Training guided the 55 hours of technical assistance delivered by the SC
      Campaign during the first year of It's Your Game, Keep It Real implementation to
      18 facilitators across 12 SC middle schools, and achieved 98.4% curriculum
      adherence and a high quality of implementation scores.

PMID- 24560074
TI  - Historical context for the creation of the Office of Adolescent Health and the
      Teen Pregnancy Prevention Program.
AB  - In Fiscal Year 2010, Federal funds were dedicated to support evidence-based
      approaches to effectively target teen pregnancy prevention and resulted in the
      establishment of the Office of Adolescent Health (OAH) and the Teen Pregnancy
      Prevention (TPP) Program. Through the tiered TPP Program, OAH supports
      replication and evaluation of programs using models whose effectiveness has been
      demonstrated through rigorous evaluation and the development and testing of
      promising or innovative pregnancy prevention strategies and approaches. This
      article documents the creation of OAH and the development of the TPP Program, the
      identification of a TPP evidence base, current program and evaluation efforts at
      OAH, and government coordination and partnerships related to reducing teen
      pregnancy. This article is of interest to those working to improve the health and
      wellbeing of adolescents. 

PMID- 24560075
TI  - Implementation lessons: the importance of assessing organizational "fit" and
      external factors when implementing evidence-based teen pregnancy prevention
      programs.
AB  - In recent years, the demand for evidence-based teen pregnancy prevention programs
      has increased, but practitioners often struggle to replicate and implement them
      as designed in real-world community settings. The purpose of this article is to
      describe the barriers and facilitators encountered during pilot year attempts to
      implement an evidence-based teen pregnancy prevention program within three types
      of organizations: (1) small community-based organizations; (2) a school-based
      organization; and (3) a large decentralized city-sponsored summer youth program.
      We frame our discussion of these experiences within the context of a systemic,
      multilevel framework for implementation consisting of (1) core implementation
      components; (2) organizational components; and (3) external factors. This article
      explores the organizational and external implementation factors we experienced
      during the implementation process, describes our lessons learned throughout this
      process, and offers strategies for other practitioners to proactively address
      these factors from the start of program planning. These findings may provide
      useful insight for other organizations looking to implement multi-session, group
      level interventions with fidelity. 

PMID- 24560076
TI  - Implementing three evidence-based program models: early lessons from the Teen
      Pregnancy Prevention Replication Study.
AB  - PURPOSE: This article describes some of the early implementation challenges faced
      by nine grantees participating in the Teen Pregnancy Prevention Replication Study
      and their response to them. METHODS: The article draws on information collected
      as part of a comprehensive implementation study. Sources include site and program
      documents; program officer reports; notes from site investigation, selection and
      negotiation; ongoing communications with grantees as part of putting the study
      into place; and semi-structured interviews with program staff. RESULTS AND
      CONCLUSIONS: The issues faced by grantees in implementing evidence-based programs
      designed to prevent teen pregnancy varied by program model. Grantees implementing
      a classroom-based curriculum faced challenges in delivering the curriculum within
      the constraints of school schedules and calendars (program length and size of
      class). Grantees implementing a culturally tailored curriculum faced a series of
      challenges, including implementing the intervention as part of the regular school
      curriculum in schools with diverse populations; low attendance when delivered as
      an after-school program; and resistance on the part of schools to specific
      curriculum content. The third set of grantees, implementing a program in clinics,
      faced challenges in identifying and recruiting young women into the program and
      in retaining young women once they were in the program. The experiences of these
      grantees reflect some of the complexities that should be carefully considered
      when choosing to replicate evidence-based programs. The Teen Pregnancy Prevention
      replication study will provide important context for assessing the effectiveness
      of some of the more widely replicated evidence-based programs.

PMID- 24560077
TI  - Beyond teacher training: the critical role of professional development in
      maintaining curriculum fidelity.
AB  - PURPOSE: To examine how teacher characteristics affected program fidelity in an
      impact evaluation study of the Positive Prevention PLUS program, and to propose a
      comprehensive teacher training and professional development structure to increase
      program fidelity. METHODS: Curriculum fidelity logs, lesson observations, and
      teacher surveys were used to measure teacher characteristics and implementation
      fidelity including adherence, adaptation, and lesson quality. RESULTS: Compared
      with non-health credentialed teachers, credential health education teachers had
      greater comfort and self-efficacy regarding sex-related instruction. Teacher self
      efficacy and comfort were significant predictors of adherence. CONCLUSIONS:
      Implementation fidelity may be linked to teacher characteristics that can be
      enhanced during curriculum training. A 2-day teacher training may not adequately
      address teacher facilitation skills or the maintenance of institutional supports
      for implementing a program with fidelity and quality. A new model of
      comprehensive teacher training and support is offered. This new training
      infrastructure is intended to contribute to the school district's
      institutionalization of higher-quality comprehensive sexual health education and
      increase program fidelity.

PMID- 24560078
TI  - Planning for a group-randomized trial with American Indian youth.
AB  - PURPOSE: To describe lessons learned working with tribal communities in the
      Northern Plains to plan and implement a group randomized trial of multimedia
      Circle of Life (mCOL), a sexual risk reduction program designed for American
      Indian (AI) youth. METHODS: Project records including emails, travel reports, and
      meeting minutes were reviewed and synthesized to describe participatory
      development of the project. RESULTS: Several challenges were identified
      including: discussing sexual health interventions for preteens with communities;
      developing a culturally appropriate research design; managing costs of conducting
      research in remote and culturally distinct tribal communities; and building
      research infrastructure of partner organizations. Opportunities for strengthening
      research partnerships included transparency, openness to bi-directional learning,
      planning for change, flexibility, and strategic use of technology. CONCLUSIONS:
      Findings suggest that meaningful AI community participation in research trials is
      achievable and a critical step towards generating evidence for interventions in
      settings where they are most needed. Substantial investments in time, resources,
      and relationship-building are necessary.

PMID- 24560079
TI  - Strong, smart and bold strategies for improving attendance and retention in an
      after-school intervention.
AB  - The Volunteers of America Greater Los Angeles (VOALA) Girls Inc. program is
      implementing and rigorously evaluating its Preventing Adolescent Pregnancy
      curriculum as part of a demonstration grant to identify effective teen pregnancy
      prevention programs sponsored by the U.S. Department of Health and Human Services
      Office of Adolescent Health (OAH). A total of 517 participants from Title I urban
      middle and high schools were randomly assigned to either Preventing Adolescent
      Pregnancy (treatment) or Economic Literacy (control) in two cohorts. Programming
      occurred after school weekly at middle and high schools. Low attendance and loss
      of sample (attrition) are common challenges in after-school programming,
      negatively affecting both the ability of a program to be successful and the
      integrity of a randomized controlled trial. The current article discusses
      challenges encountered with recruitment, incentives, and school factors during a
      first cohort of youth and innovative implementation changes during a second
      cohort that resulted in increased attendance rates and decreased attrition rates.
      Commentary is provided by the OAH Project Officer as well as lessons learned
      after 2 years of implementing the program.

PMID- 24560080
TI  - A peer education program: delivering highly reliable sexual health promotion
      messages in schools.
AB  - PURPOSE: This article describes preliminary findings from an implementation study
      of a school-based peer education program on sexual health for high-school youth.
      The responses of youth participants are described. METHODS: Qualitative data were
      collected across one semester in two successive waves of participants (N = 4
      schools), including observations of program activities, in-depth interviews of
      stakeholders, focus groups with youth participants (N = 62 peer educators and 60
      ninth graders), and brief surveys of youth participants (N = 678). Grounded
      theory methodology informed data collection and analysis. RESULTS: Teen
      Prevention Education Program (Teen PEP) was adapted and replicated with fidelity
      to the model in North Carolina high schools. All program "inputs" and five core
      model components (outputs) were implemented. The principal accommodation made was
      to implement the entire curriculum within one half of a school year rather than
      across the entire school year although still using the same amount of
      instructional time. Youth participants attributed high value to the experience,
      noting that the sexual health information they received was both new and
      important for their lives and that they felt they learned it better from their
      peers than from instruction in traditional health class. The majority of
      participants reported that the program helped them across a range of areas
      related to both social well-being and sexual health. CONCLUSIONS: Teen PEP
      developers have been able to successfully adapt and replicate it in North
      Carolina, in settings that need sexual health education services for youth both
      because of the paucity of existing services in many areas and because of the
      evidence of risk in the form of high rates of pregnancy and sexually transmitted
      infections, including human immunodeficiency virus or AIDS in youth 15-19 years
      of age. Youth reported benefits across a range of social and sexual health
      related areas.

PMID- 24560081
TI  - Enhancing a Teen Pregnancy Prevention Program with text messaging: engaging
      minority youth to develop TOP (r) Plus Text.
AB  - PURPOSE: To develop and pilot a theory-based, mobile phone texting component
      attractive to minority youth as a supplement to the Teen Outreach Program((r)), a
      youth development program for reducing teen pregnancy and school dropout.
      METHODS: We conducted iterative formative research with minority youth in
      multiple focus groups to explore interest in texting and reaction to text
      messages. We piloted a month-long version of TOP((r)) Plus Text with 96 teens at
      four sites and conducted a computer-based survey immediately after enrollment and
      at the end of the pilot that collected information about teens' values, social
      support, self-efficacy, and behaviors relating to school performance, trouble
      with the law, and sexual activity. After each of the first three weekly sessions
      we collected satisfaction measures. Upon completion of the pilot we conducted
      exit interviews with twelve purposively selected pilot participants. RESULTS: We
      successfully recruited and enrolled minority youth into the pilot. Teens were
      enthusiastic about text messages complementing TOP((r)). Results also revealed
      barriers: access to text-capable mobile phones, retention as measured by
      completion of the post-pilot survey, and a need to be attentive to teen literacy.
      CONCLUSIONS: Piloting helped identify improvements for implementation including
      offering text messages through multiple platforms so youth without access to a
      mobile phone could receive messages; rewording texts to allow youth to express
      opinions without feeling judged; and collecting multiple types of contact
      information to improve follow-up. Thoughtful attention to social and behavioral
      theory and investment in iterative formative research with extensive consultation
      with teens can lead to an engaging texting curriculum that enhances and
      complements TOP((r)).

PMID- 24560082
TI  - Engaging pregnant and parenting teens: early challenges and lessons learned from
      the Evaluation of Adolescent Pregnancy Prevention Approaches.
AB  - This article draws on data from the ongoing federal Evaluation of Adolescent
      Pregnancy Prevention Approaches to discuss the early implementation experiences
      of two new and innovative programs intended to delay rapid repeat pregnancy among
      teen mothers: (1) AIM 4 Teen Moms, in Los Angeles County, California; and (2)
      Teen Options to Prevent Pregnancy (T.O.P.P.), in Columbus, Ohio. Program staff
      report common challenges in working with teen mothers, particularly concerning
      recruitment and retention, staff capacity and training, barriers to
      participation, and participants' overarching service needs. Lessons learned in
      addressing these challenges provide useful guidance to program developers,
      providers, policy makers, and stakeholders working with similar populations. 

PMID- 24560083
TI  - What does it take? How federal initiatives can support the implementation of
      evidence-based programs to improve outcomes for adolescents.
AB  - Over the last 20 years, there has been a growing emphasis on developing and
      identifying evidence-based programs and practices for children and families and
      within the last decade an increasing number of federally funded initiatives have
      been dedicated to replicating and scaling evidence-based programs with the hope
      of achieving socially meaningful impact. However, only recently have efforts to
      promote high-fidelity implementation been given the attention needed to ensure
      evidence-based practices are used as intended and generate the outcomes they were
      designed to produce. In this article, we propose that the wide-scale
      implementation of evidence-based practices requires: (1) careful assessment and
      selection of the "what"; (2) a stage-based approach that provides adequate time
      and resources for planning and installation activities; (3) the co-creation of a
      visible infrastructure by a triad of key stakeholders including funders and
      policymakers, program developers, and implementing sites; and (4) the use of data
      to guide decision-making and foster curiosity into continuous improvement among
      grantees. Each of these strategies is explored in greater detail through the lens
      of the Teen Pregnancy Prevention (TPP) Program, a $100 million initiative
      overseen by the Office of Adolescent Health (OAH) in the U.S. Department of
      Health and Human Services. 

PMID- 24560084
TI  - Role of calprotectin in cardiometabolic diseases.
AB  - Calprotectin represents an interesting peptide known to be involved in the
      pathophysiology of various inflammatory processes. Being secreted from activated
      neutrophils and monocytes under various conditions, it can also be found in the
      extracellular fluids and serve as a biomarker of ongoing inflammation, which
      property is currently used in the monitoring of inflammatory bowel diseases.
      Recent studies, however, suggest that calprotectin could serve as an important
      prognostic factor for cardiovascular and cardiometabolic diseases, since these
      are occurring on the basis of low-grade chronic inflammation. We assume that
      calprotectin may represent a useful marker in predicting the course of
      atherosclerotic process, coronary artery disease and acute coronary syndromes.
      Our review is focused on the importance of calprotectin in the diagnosis and
      prognostic stratification in the field of cardiometabolic risk. 

PMID- 24560085
TI  - Cardiac metastasis from a urothelial cell carcinoma: a commented case report.
AB  - We present a case of a middle-aged male patient who was admitted to our
      institution because of the supposed diagnosis of endocarditis/myocarditis.
      Echocardiographic findings revealed cystic mass in the left myocardial wall as
      well as floating structures at the lateral papillary muscle, mimicking
      endocarditis/myocarditis. Due to progressive urinary retention and clinical signs
      of a beginning ileus, an abdominal and thoracic computed tomographic scan was
      performed, which demonstrated a large diverticle of the urinary bladder with
      expansive tumorous wall mass. One week later, the patient died of acute
      cardiorespiratory failure. On autopsy, the tumorous mass in the urinary bladder
      with large carcinosis of the peritoneum and multiple left and right ventricular
      metastases were confirmed; the histological analysis indicated a less
      differentiated urothelial cell carcinoma with its origin in the large diverticle
      of the urinary bladder with subsequent cardiac metastases. 

PMID- 24560086
TI  - Sarcomatoid renal cell carcinoma: clinical outcome and survival after treatment
      with sunitinib.
AB  - BACKGROUND: Renal tumors with sarcomatoid changes are aggressive malignancies
      with poor prognosis. Immunotherapy and chemotherapy have provided little benefit.
      The efficacy of treatments targeting the vascular endothelial growth factor
      pathway is unclear because of the lack of clinical trial data and the small
      number of published series. PATIENTS AND METHODS: We reviewed the clinical
      records of 23 consecutive patients with advanced sarcomatoid renal cell carcinoma
      who were treated with sunitinib in our center. Overall survival (OS), progression
      free survival, and response rate were evaluated. We also studied the effect on
      clinical outcome of performance status, prognostic risk group, and proportion of
      sarcomatoid component. RESULTS: Median OS was 15.7 months (95% confidence
      interval [CI], 5.0-21.2). Median progression-free survival was 5.7 months (95%
      CI, 3.2-12.6). Seven patients (30%) had an objective response, 5 patients (22%)
      had stable disease, and 11 (48%) had progressive disease. The median survival of
      the 13 (56.5%) patients with performance status of 0 to 1 was 20.9 months (95%
      CI, 9.7-63.3) whereas the medial survival of the 10 (43.5%) patients with
      performance status of 2 to 3 was 5.0 months (95% CI, 1.1-16.5). Objective
      responses were observed only among the 13 (56.5%) patients with performance
      status of 0 to 1. Heng prognostic risk group and percentage of sarcomatoid
      component did not influence outcome. CONCLUSION: Sunitinib shows efficacy in
      advanced renal tumors with sarcomatoid differentiation particularly in patients
      with good performance status. Appropriate patient selection and risk-directed
      treatment remains essential in this aggressive disease.

PMID- 24560087
TI  - Role of maximal endoscopic resection before cystectomy for invasive urothelial
      bladder cancer.
AB  - INTRODUCTION/BACKGROUND: The aim of this study was to examine whether TUR of all
      visible endophytic tumors performed before RC, with or without NC, affects final
      pathologic staging. PATIENTS AND METHODS: We retrospectively reviewed data from
      patients with clinical T2-T4N0-1 urothelial carcinoma of the bladder who
      underwent RC at our institution between July 2005 and November 2011. Degree of
      TUR was derived from review of operative reports. We used multivariate logistic
      regression to assess the association of maximal TUR on pT0 status at time of RC.
      RESULTS: Of 165 eligible RC patients, 81 received NC. Reported TUR of all visible
      tumors was performed in 38% of patients who did not receive NC and 48% of NC
      patients (P = .19). Nine percent of patients who underwent maximal TUR and did
      not receive NC were pT0, whereas among NC patients, pT0 was seen in 39% and 19%
      of those with and without maximal TUR, respectively (P = .05). On multivariate
      analysis in all patients, maximal TUR was associated with a nonsignificant
      increased likelihood of pT0 status (odds ratio [OR], 2.03; 95% confidence
      interval [CI], 0.84-4.94), which was significant when we restricted the analysis
      to NC patients (OR, 3.17; 95% CI, 1.02-9.83). CONCLUSION: Maximal TUR of all
      endophytic tumors before NC is associated with complete pathologic tumor response
      at RC. Candidates for NC before RC should undergo resection of all endophytic
      tumors when feasible. Larger series are warranted to see if maximal TUR leads to
      improved overall and disease-specific survival.

PMID- 24560088
TI  - Blinded interpretation of study results can feasibly and effectively diminish
      interpretation bias.
AB  - OBJECTIVE: Controversial and misleading interpretation of data from randomized
      trials is common. How to avoid misleading interpretation has received little
      attention. Herein, we describe two applications of an approach that involves
      blinded interpretation of the results by study investigators. STUDY DESIGN AND
      SETTINGS: The approach involves developing two interpretations of the results on
      the basis of a blinded review of the primary outcome data (experimental treatment
      A compared with control treatment B). One interpretation assumes that A is the
      experimental intervention and another assumes that A is the control. After
      agreeing that there will be no further changes, the investigators record their
      decisions and sign the resulting document. The randomization code is then broken,
      the correct interpretation chosen, and the manuscript finalized. Review of the
      document by an external authority before finalization can provide another
      safeguard against interpretation bias. RESULTS: We found the blinded preparation
      of a summary of data interpretation described in this article practical,
      efficient, and useful. CONCLUSIONS: Blinded data interpretation may decrease the
      frequency of misleading data interpretation. Widespread adoption of blinded data
      interpretation would be greatly facilitated were it added to the minimum set of
      recommendations outlining proper conduct of randomized controlled trials (eg, the
      Consolidated Standards of Reporting Trials statement).

PMID- 24560089
TI  - Novel presentational approaches were developed for reporting network meta
      analysis.
AB  - OBJECTIVES: To present graphical tools for reporting network meta-analysis (NMA)
      results aiming to increase the accessibility, transparency, interpretability, and
      acceptability of NMA analyses. STUDY DESIGN AND SETTINGS: The key components of
      NMA results were identified based on recommendations by agencies such as the
      National Institute for Health and Care Excellence (United Kingdom). Three novel
      graphs were designed to amalgamate the identified components using familiar
      graphical tools such as the bar, line, or pie charts and adhering to good
      graphical design principles. RESULTS: Three key components for presentation of
      NMA results were identified, namely relative effects and their uncertainty,
      probability of an intervention being best, and between-study heterogeneity. Two
      of the three graphs developed present results (for each pairwise comparison of
      interventions in the network) obtained from both NMA and standard pairwise meta
      analysis for easy comparison. They also include options to display the
      probability best, ranking statistics, heterogeneity, and prediction intervals.
      The third graph presents rankings of interventions in terms of their
      effectiveness to enable clinicians to easily identify "top-ranking"
      interventions. CONCLUSIONS: The graphical tools presented can display results
      tailored to the research question of interest, and targeted at a whole spectrum
      of users from the technical analyst to the nontechnical clinician.

PMID- 24560090
TI  - Financial and employment impacts of serious injury: a qualitative study.
AB  - OBJECTIVES: To explore the financial and employment impacts following serious
      injury. DESIGN: Semi-structured telephone administered qualitative interviews
      with purposive sampling and thematic qualitative analysis. PARTICIPANTS: 118
      patients (18-81 years) registered by the Victorian State Trauma Registry or
      Victorian Orthopaedic Trauma Outcomes Registry 12-24 months post-injury. RESULTS:
      Key findings of the study were that although out-of-pocket treatment costs were
      generally low, financial hardship was prevalent after hospitalisation for serious
      injury, and was predominantly experienced by working age patients due to
      prolonged absences from paid employment. Where participants were financially
      pressured prior to injury, injury further exacerbated these financial concerns.
      Reliance on savings and loans and the need to budget carefully to limit financial
      burden were discussed. Financial implications of loss of income were generally
      less for those covered by compensation schemes, with non-compensable participants
      requiring welfare payments due to an inability to earn an income. Most
      participants reported that the injury had a negative impact on work. Loss of
      earnings payments from injury compensation schemes and income protection
      policies, supportive employers, and return to work programs were perceived as key
      factors in reducing the financial burden of injured participants. Employer
      related barriers to return to work included the employer not listening to the
      needs of the injured participant, not understanding their physical limitations,
      and placing unrealistic expectations on the injured person. While the financial
      benefits of compensation schemes were acknowledged, issues accessing entitlements
      and delays in receiving benefits were commonly reported by participants,
      suggesting that improvements in scheme processes could have substantial benefits
      for injured patients. CONCLUSIONS: Seriously injured patients commonly
      experienced substantial financial and work-related impacts of injury.
      Participants of working age who were unemployed prior to injury, did not have
      extensive leave accrual at their pre-injury employment, and those not covered by
      injury compensation schemes or income protection insurance clearly represent
      participants "at risk" for substantial financial hardship post-injury. Early
      identification of these patients, and improved provision of information about
      financial support services, budgeting and work retraining could assist in
      alleviating financial stress after injury.

PMID- 24560091
TI  - The evolution of a purpose designed hybrid trauma operating room from the trauma
      service perspective: the RAPTOR (Resuscitation with Angiography Percutaneous
      Treatments and Operative Resuscitations).
AB  - Traumatic injury is the leading cause of potentially preventable lost years of
      life in the Western world and exsanguination is the most potentially preventable
      cause of post-traumatic death. With mature trauma systems and experienced trauma
      centres, extra-abdominal sites, such as the pelvis, constitute the most frequent
      anatomic site of exsanguination. Haemorrhage control for such bleeding often
      requires surgical adjuncts most notably interventional radiology (IR). With the
      usual paradigm of surgery conducted within an operating room and IR procedures
      within distant angiography suites, responsible clinicians are faced with making
      difficult decisions regarding where to transport the most physiologically
      unstable patients for haemorrhage control. If such a critical patient is
      transported to the wrong suite, they may die unnecessarily despite having
      potentially salvageable injuries. Thus, it seems only logical that the
      resuscitative operating room of the future would have IR capabilities making it
      the obvious geographic destination for critically unstable patients, especially
      those who are exsanguinating. Our trauma programme recently had the opportunity
      to conceive, design, build, and operationalise a purpose-designed hybrid trauma
      operating room, designated as the resuscitation with angiographic percutaneous
      techniques and operative resuscitation (RAPTOR) suite, which we believe to be the
      first such resource designed primarily to serve the exsanguinating trauma
      patient. The project was initiated after consultations between the trauma
      programme and private philanthropists regarding the greatest potential impacts on
      regional trauma care. The initial capital construction costs were thus privately
      generated but coincided with a new hospital wing construction allowing the RAPTOR
      to be purpose-designed for the exsanguinating patient. Many trauma programmes
      around the world are now starting to navigate the complex process of building new
      facilities, or else retrofitting existing ones, to address the need for single
      site flexible haemorrhage control. This manuscript therefore describes the many
      considerations in the design and refinement of the physical build, equipment
      selection, human factors evaluation of new combined treatment paradigms, and the
      final introduction of a RAPTOR protocol in order that others may learn from our
      initial efforts. 

PMID- 24560092
TI  - The pointed clamp reduction technique for spiral subtrochanteric fractures: a
      technical note.

PMID- 24560093
TI  - A new cochlear implant electrode with a "cork"-type stopper for inner ear
      malformations.
AB  - OBJECTIVE: Gusher in inner ear malformations is common in patients with
      incomplete partition type I and type III. It is also common in less severe form
      as oozing in incomplete partition type II and large vestibular aqueduct. It is
      important to prevent cerebrospinal fluid (CSF) escape around the electrode to
      prevent meningitis. METHODS: The custom-made device was produced by Med-El
      Company. It has a "cork"-like stopper instead of the usual silicon ring to
      prevent gusher. There are two types of electrodes of different lengths. The
      standard one is 25mm (contact space 1.7mm) and the short one is 20mm (contact
      space 1.3mm). It was used in 50 patients with different inner ear malformations.
      RESULTS: Thirteen patients had gusher, and 11 patients oozing during
      cochleostomy. One patient with initial prototype of the cork electrode had to be
      revised because of persistent oozing around the electrode. Another patient had
      slow extrusion of the electrode most probably due to CSF pulsation and had to be
      revised. Both patients had no more CSF fistula. CONCLUSION: CSF fistula in inner
      ear malformations is a serious situation which may lead to recurrent meningitis.
      The new electrode with "cork" stopper looks promising in preventing the
      postoperative CSF leak around the electrode.

PMID- 24560094
TI  - Predictor of rehabilitation outcome for dysphagia.
AB  - OBJECTIVE: Predicting whether dysphagia will resolve is very difficult, but is
      obviously important for patients and their families as well as for physicians.
      This study retrospectively evaluated potential prognostic indicators for
      dysphagia in order to examine the feasibility of predicting the outcome. METHODS:
      Data on 123 patients who received initial treatment for dysphagia between April
      2008 and March 2010 were reviewed. The patient population included 63 men and 60
      women, with a mean age of 81.4 years. All the patients underwent physical
      examination and video-endoscopy (VE) at the initial assessment, and video
      fluorography (VF) was also done if necessary. We used the "Food Intake Level
      Scale" (FILS) to classify the severity of dysphagia as follows: "no oral intake"
      (FILS score: 1-3), "oral intake and alternative nutrition" (FILS score: 4-6), and
      "oral intake alone" (FILS score: 7-10). The patient's age, primary disease,
      cognitive ability, and general condition were evaluated as potential factors
      associated with the severity of dysphagia. Each patient underwent assessment at
      every 2 weeks to evaluate the progress of their dysphagia. RESULTS: Forty-six
      patients were classified as "no oral intake" (FILS score: 1-3) at the initial
      examination and subsequently showed improvement to "oral intake and alternative
      nutrition" (FILS score: 4-6) or "oral intake alone" (FILS score: 7-10). They were
      compared with 43 patients who were also "no oral intake" at the second
      examination after training in swallowing. The combination of stroke and cognitive
      dysfunction showed a sensitivity of 75.9% (22/29) and specificity of 78.3%
      (18/23) for predicting no improvement of dysphagia, and was a statistically
      significant parameter. The presence of disuse syndrome showed a sensitivity of
      66.0% (31/47) and specificity of 71.4% (30/42) for predicting no improvement of
      dysphagia, and this was also a significant parameter. CONCLUSION: The results of
      this study suggest that a combination of factors other than stroke, including
      cognitive dysfunction and a decrease in activity of daily living (ADL) influence
      the outcome of dysphagia. It is not rare for patients who resume oral intake to
      be readmitted within a year for symptoms such as fever. Therefore, effective
      rehabilitation programs should be developed for the impairments of elderly
      patients and common disabilities such as dysphagia.

PMID- 24560095
TI  - The sense of coherence in patients with Meniere's disease.
AB  - OBJECTIVE: To investigate how the ability to adapt, measured by the sense of
      coherence (SOC), is related to specific complaints of Meniere's disease (MD) and
      the disease specific and general health related quality of life (EQ-5D) and on
      disease specific impact of the disease (MD-impact). METHODS: Postal survey,
      including a structured questionnaire on EQ-5D, SOC, symptoms, positive
      experiences, and the impact of MD, was sent to the members of the Finnish Meniere
      Federation, reporting a diagnosis compatible with the condition. A sample of 547
      members replied and were analyzed. RESULTS: The SOC reflected the disabilities
      caused by symptoms of MD and psychosocial factors including verbal score scale
      (VSS) anxiety (p<0.01) and loss of vitality (p<0.001). Higher SOC scores were
      related to better scores in EQ-5D and lower scores in MD-impact. Positive
      attitudes consequential to MD were associated with higher SOC scores reflecting
      better control over the consequences of disease. CONCLUSION: SOC is an element of
      patient's attitude toward illness and correlates with perceived good health.
      Patients with higher SOC scores are more content with their quality of life.
      Future research should focus on whether influencing modifiable psychological
      factors, such as positive attitudes, could improve adaptive ability in MD.

PMID- 24560096
TI  - Cochlear implantation in a patient with acute myelomonocytic leukemia before
      allogeneic peripheral blood stem cell transplantation.
AB  - Bilateral deafness can occur in patients with acute leukemia and it can cause
      communication problems and depressed mood during the treatment of leukemia.
      Cochlear implantation (CI) is the choice of hearing rehabilitation; however,
      there is scarce information about the safety of CI during the treatment of
      leukemia. A 50-year-old female leukemia patient was successfully implanted with a
      Nucleus cochlear implant while in complete remission before peripheral blood stem
      cell transplantation. Until now, with a follow-up of 4 years, the patient has
      useful hearing perception without any complications. To our knowledge, this is
      the first reported case of a successful CI in a patient with acute leukemia
      during the treatment of leukemia. 

PMID- 24560097
TI  - In vitro functional characterization of feline IgGs.
AB  - Very little is known about the functional properties of feline IgGs. Here we
      report the in vitro characterization of cloned feline IgGs. Rapid amplification
      of cDNA ends (RACE) and full-length PCR of cat splenic cDNA were used to identify
      feline sequences encoding IgG heavy chain constant regions (IGHC). Two of the
      sequences are possibly allelic and have been previously reported in the
      literature as the only feline IgG, IgG1. Although we confirmed these alleles to
      be highly abundant (~98%), analysis of numerous amplification products revealed
      an additional sequence (~2%). We cloned and characterized chimeric monoclonal
      antibodies with each of these heavy chains. Using RACE we revealed the sequences
      for feline Fc gamma receptor I (FcgammaRI) and feline Fc neonatal receptor
      (FcRn). We constructed these recombinant receptors as well as fFcgammaRIII and
      determined their binding affinities to the chimeras. All of the chimeras bound to
      Protein A but not to Protein G, and bound tightly to fFcRn (KD=2-5 nM). Both IgG1
      alleles have a high affinity for fFcgammaRI (KD=10-20 nM), they bind to the low
      affinity fFcgammaRIII receptor (2-4 MUM), and also bind to human complement C1q.
      Thus, feline IgG1a and 1b are expected to induce strong effector function in
      vivo. The additional IgG detected does not bind to recombinant fFcgammaRI or
      fFcgammaRIII and has negligible binding to hC1q. Consequently, although this
      putative subclass is projected to have a similar serum half-life as the IgG1
      alleles based on comparable in vitro affinity to FcRn, it may not elicit the
      effector responses mediated by fFcgammaRI or fFcgammaRIII. Further testing with
      native receptors and functional cell-based assays would confirm effector function
      capabilities of feline IgG subclasses; however this is the first report
      characterizing affinities of feline IgGs to their Fc receptors and helps pave the
      way for construction of feline-specific IgGs for therapeutic use.

PMID- 24560098
TI  - Compulsory schooling reforms, education and mortality in twentieth century
      Europe.
AB  - Education yields substantial non-monetary benefits, but the size of these gains
      is still debated. Previous studies report causal effects of education and
      compulsory schooling on mortality ranging anywhere from zero to large and
      negative. Using data from 18 compulsory schooling reforms implemented in Europe
      during the twentieth century, we quantify the average mortality gain and explore
      its dispersion across gender, time and countries. We find that more education
      yields small mortality reductions in the short- and long-run for men. In
      contrast, women seem to experience no mortality reductions from compulsory
      schooling reforms. 

PMID- 24560099
TI  - Inclusiveness in the health economic evaluation space.
AB  - This paper presents an overview of Gavin Mooney's contributions to broadening the
      evaluative space in health economics. It outlines how Mooney's ideas have
      encouraged many, including ourselves, to expand the conventional QALYs/health
      gain approach and look more broadly at what it is that is of value from health
      services. We reflect on Mooney's contributions to debates around cost
      effectiveness analysis, Quality Adjusted Life Years (QALYs) and cost-utility
      analysis as well as his contribution to the development and application of
      contingent valuation and discrete choice experiments in health economics. We
      conclude by suggesting important avenues for future research to take forward
      Mooney's work. 

PMID- 24560100
TI  - Celebrating the work of Gavin Mooney: inclusiveness and involvement in global and
      public health issues.
AB  - This paper considers Gavin Mooney's contributions to the research literature on
      inclusiveness in global and public health issues. Much of his contribution in
      this area stems from engaging with Indigenous people, which cemented his
      conviction that it is important to recognise the heterogeneity of groups in
      society, especially in relation to cultural differences. He believed that in
      order to develop appropriate equitable and efficient health and related policies,
      the preferences of citizens should be elicited. While this could feed into very
      specific policy decisions, such as how to allocate available resources within a
      particular community, more generally, community preferences should determine the
      core values that underpin a health system. He proposed that these values be
      documented in a 'constitution' and serve as the basis on which policy-makers and
      health managers make decisions. Preference elicitation has value in itself, as
      procedural justice allows for self-determination and contributes to empowerment.
      Further, engagement by citizens in deliberative processes can overcome
      polarisation. Health systems themselves, if developed as social institutions, can
      influence the nature of society and contribute to greater unity. Mooney raised
      similar concerns about policies arising from mono-cultural global perspectives
      and argued that, whether at the national or global level, values for health
      systems should be based on community preferences. He particularly highlighted the
      unequal distribution of benefits of neoliberal globalisation as the cause of
      growing health and wealth inequalities globally. There is resonance between
      Mooney's views on these issues and some of the contributions to the post-2015
      development agenda debates. While it is unlikely that we have reached a point
      where the stranglehold of neo-liberal governments on key global institutions will
      be broken, the current debates nevertheless present an important window of
      opportunity to struggle for shifts in the global political economy. Current
      debates about universal coverage also provide a critical opportunity to move
      towards health systems that are built on values determined by citizens and are
      social institutions that build solidarity, redress inequalities and unite
      fractured societies. 

PMID- 24560101
TI  - Tragic, but not random: the social contagion of nonfatal gunshot injuries.
AB  - This study investigates the concentration of nonfatal gunshot injuries within
      risky social networks. Using six years of data on gunshot victimization and
      arrests in Chicago, we reconstruct patterns of co-offending for the city and
      locate gunshot victims within these networks. Results indicate that 70 percent of
      all nonfatal gunshot victims during the observation period can be located in co
      offending networks comprised of less than 6 percent of the city's population.
      Results from logistic regression models suggest that as an individual's exposure
      to gunshot victims increases, so too do that individual's odds of victimization.
      Furthermore, even small amounts of exposure can dramatically increase the odds of
      victimization. For instance, every 1 percent increase in exposure to gunshot
      victims in one's immediate network increases the odds of victimization by roughly
      1.1 percent, holding all else constant. These observed associations are more
      pronounced for young minority males, and effects of exposure extend to indirect
      network ties at distances of two to three steps removed. These findings imply
      that the risk of gunshot victimization is more concentrated than previously
      thought, being concentrated in small and identifiable networks of individuals
      engaging in risky behavior, in this case criminal activity. 

PMID- 24560102
TI  - Design and development of sustainable remediation process for mitigation of
      fluoride contamination in ground water and field application for domestic use.
AB  - Decentralised household chemo defluoridation unit (CDU) was developed and
      designed based on a combination of coagulation and sorption processes. Chemo
      defluoridation process was optimised to reduce use of chemicals and increase
      acceptability among beneficiaries without affecting palatability of water.
      Chemical dose optimization undertaken in the laboratory using jar test revealed
      the optimum calcium salt to initial fluoride ratio of 60 for fluoride removal.
      Performance of CDU was evaluated in the laboratory for removal efficiency, water
      quality parameters, filter bed cleaning cycle and desorption of fluoride. CDU
      evaluation in the laboratory with spiked water (5 mg/L) and field water (~4.2
      mg/L) revealed treated water fluoride concentration of less than 1mg/L. Seventy
      five CDUs were installed in households at Sakhara Village, Yavatmal District in
      Maharashtra State of India. Monthly monitoring of CDUs for one year indicated
      reduction of the raw water fluoride concentration from around 4 mg/L to less than
      1mg/L. Post implementation survey after regular consumption of treated drinking
      water by the users for one year indicated user satisfaction and technological
      sustainability.

PMID- 24560103
TI  - Response to the letter to the editor by Rasmussen and Mech, 2014: better
      understanding of the EU regulatory frameworks for cosmetic products.

PMID- 24560104
TI  - Proposal of performance objectives and sampling schemes for Listeria
      monocytogenes in fresh meat intended to be eaten cooked under different storage
      practices.
AB  - The goal of this study was to define a practical approach to derive risk
      management measures, such as performance objectives (POs), for Listeria
      monocytogenes in pork cuts intended to be eaten cooked. Moreover, sampling plans
      to verify the compliance of meat lots to such POs are presented. The POs were
      estimated as prevalence and/or concentration values that should not be exceeded
      at time of consumption. To derive possible POs for L. monocytogenes, ten lots of
      pork cuts, collected within the same slaughterhouse along a one-year period, were
      tested for the presence and concentration of the pathogen under four different
      scenarios through the product shelf life. Our results indicated that the median
      values of the prevalence distributions ranged between 0.41 and 0.68. The number
      of samples to be tested in order to verify lot compliance ranged between six, for
      samples tested immediately after packaging, and three, for samples tested at the
      end of the shelf life. The concentration values ranged between 2.02 log10 CFU/g,
      for samples tested immediately after packaging, up to 3.14 log10 CFU/g for
      samples tested after final storage at 14 degrees C. The concentration of L.
      monocytogenes in the samples contaminated by less than 10 CFU/g was estimated
      between 7 CFU/10g to 7 CFU/g, after storage at retail and abuse temperature,
      respectively. Basing on the knowledge of log normal distributions, the maximum
      contamination level of the lots in order to achieve the suggested POs, was
      calculated. It was obtained that mean concentration estimated as PO should be
      between -0.43 and 0.48 log10 CFU/g. Other risk management options are further
      evaluated and discussed. These results would help food operators and authorities
      to establish safety targets and corrective actions regarding inhibition of L.
      monocytogenes in fresh pork meat.

PMID- 24560105
TI  - Epidemiology and risk factors of biliary tract and primary liver tumors.
AB  - Primary liver and biliary tract tumors encompass a range of benign and malignant
      neoplasms. They consist of histologically distinct types of tumors that arise
      from and are influenced by hepatocytes, biliary epithelial cells, and mesenchymal
      cells. Improvements in imaging have allowed the detection and diagnosis of these
      neoplasms to be refined. Investigation at the histologic, molecular, and genetic
      levels has allowed neoplasms to be categorized and treated. Epidemiology has
      improved understanding of geographic, ethnic, gender, and cultural differences
      that link exposures with cancer risk. This article focuses on the epidemiology of
      major primary adult liver and biliary tract tumors. 

PMID- 24560106
TI  - Imaging of the patient with a biliary tract or primary liver tumor.
AB  - Cross-sectional imaging can be useful in the diagnosis of biliary tract and
      primary liver tumors. Hepatobiliary tumors are diverse in growth patterns,
      histologic types and tumor location. A fundamental understanding of the imaging
      features of hepatobiliary tumors is critical for diagnosis, staging and
      treatment. Knowledge about various manifestations and mimickers of biliary and
      primary liver tumors is essential for tumor diagnosis and suitable management.
      Magnetic resonance imaging and computed tomography technology continues to
      rapidly evolve and these tools not only aid in evaluation and treatment, but also
      can potentially define response to therapy and overall patient prognosis. 

PMID- 24560107
TI  - Endoscopic and percutaneous approaches to the treatment of biliary tract and
      primary liver tumors: controversies and advances.
AB  - Advances in percutaneous and endoscopic techniques have improved preoperative
      selection and optimization in patients with biliary and liver tumors, but are not
      without their own controversies. Selective rather than routine preoperative
      biliary drainage (PBD) should be employed, as PBD may be associated with
      increased infectious complications. Endoscopic ampullectomy (EA) offers
      advantages in morbidity and mortality over surgical approaches and should be the
      first line therapy for benign ampullary lesions. Ampullary cancers require
      pancreaticoduodenectomy. Effectiveness of percutaneous ablative techniques is
      dependent on tumor size and can be used as palliative therapy, as a bridge to
      transplantation, or, in select situations, as definitive therapy. 

PMID- 24560109
TI  - Hilar cholangiocarcinoma.
AB  - Optimal treatment of hilar cholangiocarcinoma depends on location of the cancer
      and extent of biliary and vascular involvement. Candidates for resection or
      transplantation must be evaluated and managed by a multidisciplinary team at a
      high-volume hepatobiliary center. Success requires absence of distant nodal or
      extrahepatic metastases and an adequate functional liver remnant with a negative
      ductal margin. Ipsilateral portal vein resection and reconstruction should be
      performed in patients with venous involvement. Neoadjuvant chemoradiation and
      liver transplantation is the best treatment option for patients with unresectable
      hilar cholangiocarcinoma without nodal or distant metastases and for patients
      with underlying chronic liver disease. 

PMID- 24560110
TI  - Distal cholangiocarcinoma.
AB  - Distal cholangiocarcinoma is an uncommon malignancy and early diagnosis remains a
      challenge. More accurate diagnostic modalities for early-stage diagnosis are
      needed. Advances in medical therapy and neoadjuvant treatment may aid surgery and
      further improve postoperative outcomes. Margin-negative resection in conjunction
      with thorough nodal dissection is the strongest prognostic factor. Surgical
      resection coupled with adjuvant therapy provides the most favorable outcome.
      Future efforts should be aimed at reducing surgical complications and improving
      medical therapy, leading to overall improvement in perioperative and long-term
      outcomes for patients with this disorder. 

PMID- 24560108
TI  - Intrahepatic cholangiocarcinoma.
AB  - Intrahepatic cholangiocarcinoma (ICC) is a rare tumor, with an increasing
      incidence worldwide and an overall poor prognosis. Symptoms are usually
      nonspecific, contributing to an advanced tumor stage at diagnosis. The staging
      system for ICC has recently been updated and is based on number of lesions,
      vascular invasion, and lymph node involvement. Complete surgical resection to
      negative margins remains the only potentially curable treatment for ICC.
      Gemcitabine-based adjuvant therapy can be offered based on limited data from
      patients with unresectable ICC. Overall 5-year survivals after resection range
      from 17% to 44%, with median survivals of 19 to 43 months.

PMID- 24560111
TI  - Hepatocellular carcinoma: diagnosis, management, and prognosis.
AB  - The successful management of hepatocellular carcinoma (HCC) requires a
      multidisciplinary approach, incorporating hepatologists, oncologists, surgical
      oncologists, transplant surgeons, and radiologists. With improvements in
      technology and better long-term outcomes data, management strategies for HCC have
      become more methodical and more successful. This article focuses on some of the
      most critical advances relating to carcinogenesis, surveillance, and management. 

PMID- 24560112
TI  - Staging of biliary tract and primary liver tumors.
AB  - For patients with hepatobiliary malignancies, various therapeutic options are
      currently available. To optimize the selection of these treatment options,
      adequate stratification of patients according to their prognosis is practically
      important. Various staging systems have been introduced and used for
      hepatobiliary malignancies. However, current staging systems have strengths and
      limitations, and none have addressed both patient prognosis and the best
      treatment strategy for individual patients. Hepatic function is also a potent
      prognostic factor for patients with hepatobiliary malignancies. Therefore,
      interpretation of tumor staging and selection of treatment should be done with
      care, understanding individual characteristics of each staging system. 

PMID- 24560113
TI  - Transarterial therapies for primary liver tumors.
AB  - Over the last decade, transarterial therapies have gained worldwide acceptance as
      standard of care for inoperable primary liver cancer. Survival times after
      transarterial chemoembolization (TACE) continue to improve as the technique and
      selection criteria are refined. Transarterial treatments, frequently provided in
      an outpatient setting, are now safely and effectively being applied to patients
      with even advanced malignancy or partially decompensated cirrhosis. In the coming
      years, newer transarterial therapies such as radiation segmentectomy, boosted
      transarterial radioembolzation, combined TACE-ablation, TACE-portal vein
      embolization, and transarterial infusion of cancer-specific metabolic inhibitors
      promise to continue improving survival and quality of life. 

PMID- 24560114
TI  - An emerging role for radiation therapy in the treatment of hepatocellular
      carcinoma and intrahepatic cholangiocarcinoma.
AB  - Radiation therapy is emerging as a potentially effective treatment of locally
      advanced, unresectable hepatocellular carcinoma (HCC). Outcomes from early
      prospective studies seem promising, with improved survival compared with
      historical controls. Cure of early stage and unresectable HCC may be possible
      with high-quality radiation therapy. Many questions remain, including
      determination of the ideal radiation dose and fractionation schema, optimal
      patient selection criteria based on tumor size, tumor location, extent of
      vascular invasion, and baseline liver function, and the role of radiation therapy
      compared with other localized standard treatments including radiofrequency
      ablation or transarterial chemoembolization. 

PMID- 24560115
TI  - Systemic and targeted therapy for biliary tract tumors and primary liver tumors.
AB  - Tumors of the biliary tract and hepatocellular carcinoma (HCC) are complex tumors
      with heterogeneous carcinogenic mechanisms. Patients with hepatobiliary cancer
      have advances disease and need systematic therapy to palliate symptoms and extend
      survival. Development of effective systematic therapy is a significant unmet
      medical need. It is hoped that current and future clinical trials will identify
      additional effective systemic agents, combination systemic therapies, and
      combined modality options. The HCC community needs validated biomarkers to help
      identify the patients who will benefit most from emerging treatment options. 

PMID- 24560116
TI  - Palliation: treating patients with inoperable biliary tract and primary liver
      tumors.
AB  - This article summarizes the current literature in treatment of unresectable
      biliary tract and primary liver tumors. Locoregional therapies including
      radiofrequency ablation, percutaneous ethanol injection, cryoablation, microwave
      ablation, transarterial chemoembolization, hepatic artery infusion,
      radioembolization ((90)Y), and bland embolization are discussed and clinical
      trials compared. Palliative strategies including surgical, percutaneous, and
      endoscopic techniques to decompress the biliary system and improve symptoms are
      also summarized. Systemic chemotherapy and sorafenib used in conjunction with
      locoregional therapies or as sole therapeutic options are discussed. 

PMID- 24560117
TI  - Surgical Oncology Clinics of North America. Biliary tract and primary liver
      tumors. Foreword.

PMID- 24560118
TI  - Biliary tract and primary liver tumors.

PMID- 24560119
TI  - [Humerus varus: correction by proximal valgus osteotomy with precontourned plate
      fixation in children].
AB  - Varus deformity of the proximal humerus in children is a little known pathology
      due to its low incidence of presentation. Progress has been made in recent years
      in understanding the possible etiology and pathophysiological causes.
      Radiological criteria for diagnosis and functional impairment that occurs have
      also been defined. However, there are few reports in the literature about the
      surgical treatment of this deformity in children. In this paper we present a case
      of surgical treatment of this deformity by corrective osteotomy fixed with
      precontoured external maleolar plate osteosynthesis. 

PMID- 24560120
TI  - Breast cancer treatment experiences by race and location in Georgia's Women's
      Health Medicaid Program.
AB  - BACKGROUND: This study seeks to understand the breast cancer treatment patterns
      and experiences of women enrolled in Georgia's Breast and Cervical Cancer
      Prevention and Treatment Act program, the Women's Health Medicaid Program (WHMP),
      and whether these experiences vary by race or location. METHODS: We conducted a
      mixed-methods analysis of WHMP breast cancer enrollees by race and urban/rural
      location. Quantitative analysis used a hazard rate model approach to identify
      differences in the timing of diagnosis, enrollment into Medicaid, and various
      modalities of treatment for 810 enrollees. Qualitative analysis used a systematic
      retrieval and review of coded data from 34 in-depth disease life history
      interview transcripts to a complete, focused analysis of enrollees' cancer
      treatment experiences. FINDINGS: African-American women began treatment, on
      average, 6 days later after diagnosis than White women, driven by delays of one
      month among African-American women with late-stage cancers. This time delay for
      African-American women was not significant on multivariate analysis of time from
      enrollment to treatment. Once enrolled in WHMP, women reported gaining access to
      equitable breast cancer treatment regardless of race or location, with the
      exception of breast reconstruction, for which some women in our sample reported
      barriers to care. CONCLUSIONS: The equitable access to cancer treatment and other
      health services provided by WHMP to low-income, uninsured women in Georgia with
      breast cancer makes it a critical health care safety net program in Georgia, the
      need for which will continue through the implementation of the Affordable Care
      Act.

PMID- 24560121
TI  - Strategies used by breast cancer survivors to address work-related limitations
      during and after treatment.
AB  - BACKGROUND: The primary objective of this exploratory study was to delineate the
      broad range of adjustments women breast cancer survivors draw upon to minimize
      cancer-related limitations at the workplace. The study also analyzed whether
      survivors used strategies to address work-related limitations in isolation or in
      combination with other strategies, and whether they used formal or informal
      strategies. METHODS: Semi-structured, in-depth interviews were conducted with 14
      women who were employed at the time of diagnosis of breast cancer and who
      continued to work during treatment or returned to work. Interviews were conducted
      3 to 24 months after diagnosis. An iterative process was used to systematically
      analyze the data (the transcripts) using qualitative methods. FINDINGS:
      Participants who worked during or after treatment adjusted their work schedule,
      performed fewer or other tasks, modified or changed their work environment,
      reduced non-work activities at the workplace, used cognitive prompts, and acted
      preemptively to make work tasks manageable after their return to work. Survivors
      used multiple adjustments and drew upon both formal and informal tactics to
      minimize or prevent cancer- or treatment-related effects from negatively
      affecting job performance. CONCLUSIONS: Knowledge about the broad range of both
      formal and informal strategies identified in this study may enable health care
      and social services providers, as well as cancer survivors and employers, to
      identify a wide range of specific strategies that may reduce the negative effects
      of work-related limitations in specific work settings. Insights gained from this
      analysis should inform future research on work and cancer survivorship.

PMID- 24560123
TI  - Abnormal erythropoiesis and the pathophysiology of chronic anemia.
AB  - Erythropoiesis, the bone marrow production of erythrocytes by the proliferation
      and differentiation of hematopoietic cells, replaces the daily loss of 1% of
      circulating erythrocytes that are senescent. This daily output increases
      dramatically with hemolysis or hemorrhage. When erythrocyte production rate of
      erythrocytes is less than the rate of loss, chronic anemia develops. Normal
      erythropoiesis and specific abnormalities of erythropoiesis that cause chronic
      anemia are considered during three periods of differentiation: a) multilineage
      and pre-erythropoietin-dependent hematopoietic progenitors, b) erythropoietin
      dependent progenitor cells, and c) terminally differentiating erythroblasts.
      These erythropoietic abnormalities are discussed in terms of their
      pathophysiological effects on the bone marrow cells and the resultant changes
      that can be detected in the peripheral blood using a clinical laboratory test,
      the complete blood count. 

PMID- 24560122
TI  - Antiparasitic activity and effect of casearins isolated from Casearia sylvestris
      on Leishmania and Trypanosoma cruzi plasma membrane.
AB  - Leishmaniasis and Chagas disease are infectious diseases caused by parasite
      Leishmania sp. and Trypanosoma cruzi, respectively, and are included among the
      most neglected diseases in several underdeveloped and developing countries, with
      an urgent demand for new drugs. Considering the antiparasitic potential of MeOH
      extract from leaves of Casearia sylvestris Sw. (Salicaceae), a bioguided
      fractionation was conducted and afforded four active clerodane diterpenes
      (casearins A, B, G, and J). The obtained results indicated a superior efficacy of
      tested casearins against trypomastigotes of T. cruzi, with IC50 values ranging
      from 0.53 to 2.77 MUg/ml. Leishmania infantum promastigotes were also susceptible
      to casearins, with IC50 values in a range between 4.45 and 9.48 MUg/ml. These
      substances were also evaluated for mammalian cytotoxicity against NCTC cells
      resulting in 50% cytotoxic concentrations (CC50) ranging from 1.46 to 13.76
      MUg/ml. Additionally, the action of casearins on parasite membranes was
      investigated using the fluorescent probe SYTOX Green. The obtained results
      demonstrated a strong interaction of casearins A and B to the plasma membrane of
      T. cruzi parasites, corroborating their higher efficacy against these parasites.
      In contrast, the tested casearins induced no alteration in the permeability of
      plasma membrane of Leishmania parasites, suggesting that biochemical differences
      between Leishmania and T. cruzi plasma membrane might have contributed to the
      target effect of casearins on trypomastigotes. Thus, considering the importance
      of studying novel and selective drug candidates against protozoans, casearins A,
      B, G, and J could be used as tools to future drug design studies.

PMID- 24560124
TI  - Progress and prospects for targeting Hsp90 to treat fungal infections.
AB  - Fungal pathogens pose a major threat to human health worldwide. They infect
      billions of people each year, leading to at least 1.5 million deaths. Treatment
      of fungal infections is difficult due to the limited number of clinically useful
      antifungal drugs, and the emergence of drug resistance. A promising new strategy
      to enhance the efficacy of antifungal drugs and block the evolution of drug
      resistance is to target the molecular chaperone Hsp90. Pharmacological inhibitors
      of Hsp90 function that are in development as anticancer agents have potential to
      be repurposed as agents for combination antifungal therapy for some applications,
      such as biofilm infections. For systemic infections, however, effective
      combination therapy regimens may require Hsp90 inhibitors that can selectively
      target Hsp90 in the pathogen, or alternate strategies to compromise function of
      the Hsp90 chaperone machine. Selectively impairing Hsp90 function in the pathogen
      could in principle be achieved by targeting Hsp90 co-chaperones or regulators of
      Hsp90 function that are more divergent between pathogen and host than Hsp90.
      Antifungal combination therapies could also exploit downstream effectors of Hsp90
      that are critical for fungal drug resistance and virulence. Here, we discuss the
      progress and prospects for establishing Hsp90 as an important therapeutic target
      for life-threatening fungal infections.

PMID- 24560125
TI  - Primary intraocular lymphoma.
AB  - Primary intraocular lymphoma (PIOL) is an ocular malignancy that is a subset of
      primary central system lymphoma (PCNSL). Approximately one-third of PIOL patients
      will have concurrent PCNSL at presentation, and 42-92% will develop PCNSL within
      a mean of 8-29 months. Although rare, the incidence has been rising in both
      immunocompromised and immunocompetent populations. The majority of PIOL is
      diffuse large B-cell lymphoma, though rare T-cell variants are described.
      Recently, PIOL has been classified by main site of involvement in the eye, with
      vitreoretinal lymphoma as the most common type of ocular lymphoma related to
      PCNSL. Diagnosis remains challenging for ophthalmologists and pathologists. PIOL
      can masquerade as noninfectious or infectious uveitis, white dot syndromes, or
      occasionally as other neoplasms such as metastatic cancers. Laboratory diagnosis
      by cytology has been much aided by the use of immunocytochemistry, flow
      cytometry, biochemical finding of interleukin changes (IL10:IL6 ratio > 1), and
      cellular microdissection with polymerase chain reaction amplification for
      clonality. Use of several tests improves the diagnostic yield. Approaches to
      treatment have centered on systemic methotrexate-based chemotherapy, often with
      cytarabine (Ara-C) and radiotherapy. Use of intravitreal chemotherapy with
      methotrexate (0.4 mg/0.1 mL) is promising in controlling ocular disease, and
      intravitreal rituximab (anti-CD20 monoclonal antibody) has also been tried.
      Despite these advances, prognosis remains poor. 

PMID- 24560126
TI  - Urrets-Zavalia syndrome (fixed and dilated pupil following penetrating
      keratoplasty for keratoconus) and its variants.
AB  - Urrets-Zavalia Syndrome (UZS) was described 50 years ago as the appearance of a
      fixed and dilated pupil following penetrating keratoplasty for keratoconus in
      patients receiving atropine. The mechanism of UZS has still not been fully
      determined, but an acute increase in intraocular pressure and ischemia of the
      iris most probably play a major role. Fixed and dilated pupils also occur in
      association with other ophthalmic surgeries, such as lamellar keratoplasties,
      cataract surgery, and glaucoma procedures. Some have questioned the existence of
      this syndrome, as well as the linkage to keratoconus and use of mydriatics. We
      review the pathophysiology, etiology, and clinical presentation of fixed and
      dilated pupils following ophthalmic procedures. 

PMID- 24560127
TI  - Gender disparities in utilization and outcome of comprehensive substance abuse
      treatment among racial/ethnic groups.
AB  - This study examined gender differences within Black, Latino, and White subgroups
      in the utilization of comprehensive services and their relation to posttreatment
      substance use. Survey data were collected during the National Treatment
      Improvement Evaluation Study (NTIES), a prospective, longitudinal, multisite
      study of substance abuse treatment programs and their clients in the United
      States. The analytic sample consisted of 1,812 blacks (734 women and 1,078 men),
      486 Latinos (147 women and 339 men), and 844 whites (147 women and 339 men) from
      59 service delivery organizations. Results related to service utilization
      indicated that compared to men, women in all racial and ethnic groups needed and
      received more services targeted to their needs and reported more positive
      relations with service providers. Gender was a significant moderator of the
      relationship between service receipt and treatment outcomes for all racial and
      ethnic groups, but especially for the Latino subsample. Findings point to the
      need to consider race-specific gender differences in the development of
      culturally competent, comprehensive substance abuse treatment.

PMID- 24560128
TI  - Prospective associations among approach coping, alcohol misuse and psychiatric
      symptoms among veterans receiving a brief alcohol intervention.
AB  - Brief alcohol interventions (BAIs) target alcohol consumption and may exert
      secondary benefits including reduced depression and posttraumatic stress disorder
      (PTSD) symptoms among non-veteran and veteran populations. This study examined
      whether approach coping, alcohol misuse, and an interaction of these two factors
      prior to the administration of a BAI (i.e., baseline) would predict depression
      and PTSD symptoms 6-months post BAI (i.e., follow-up). Veterans (N=166) received
      a BAI after screening positive for alcohol misuse during a primary care visit and
      completed assessments of alcohol misuse, approach coping, and depression and PTSD
      symptoms at baseline and follow-up. Baseline substance misuse, but not approach
      coping, significantly predicted depression and PTSD symptoms at follow-up.
      Approach coping moderated associations between baseline alcohol misuse and
      psychiatric symptoms: Veterans reporting more alcohol misuse and more (relative
      to less) approach coping at baseline evidenced fewer psychiatric symptoms at
      follow-up after accounting for symptoms assessed at baseline. 

PMID- 24560129
TI  - Factors associated with buprenorphine compared to amphetamine abuse among clients
      seeking treatment in Finland.
AB  - Abuse of prescription opioids is becoming increasingly widespread. This study
      compared the social, health and treatment-related factors associated with
      buprenorphine and amphetamine abuse in Finland. Structured clinical interviews
      were conducted with clients seeking treatment for buprenorphine (n=670) or
      amphetamine (n=557) abuse in Helsinki from January 2001 to August 2008.
      Unadjusted and adjusted odds ratios (ORs) with 95% confidence intervals (CIs)
      were computed for factors associated with buprenorphine compared to amphetamine
      abuse. In multivariate analyses, buprenorphine abuse was associated with male
      gender (OR 1.57, 95% CI 1.17-2.09), daily abuse (OR 5.45, 95% CI 4.14-7.18), no
      drug free months during the last year (OR 1.68, 95%CI 1.23-2.29), and inversely
      associated with increasing age (OR 0.95, 95% CI 0.93-0.97 per year) and psychotic
      symptoms (OR 0.33, 95% CI 0.24-0.45). Despite more intense abuse patterns,
      clients seeking treatment for buprenorphine abuse shared similar characteristics
      to amphetamine clients. These characteristics were different to characteristics
      of those who abuse prescription opioids in North America. This is important for
      developing and targeting intervention programs.

PMID- 24560130
TI  - Infant with subcutaneous tumor in the genital area.

PMID- 24560131
TI  - Event-related mu-rhythm desynchronization during movement observation is impaired
      in Parkinson's disease.
AB  - OBJECTIVE: Patients with Parkinson's disease often experience difficulties in
      adapting movements and learning alternative movements to compensate for symptoms.
      Since observation of movement has been demonstrated to lead to the formation of a
      lasting specific motor memory that resembled that elicited by physical training
      we hypothesize that mu-rhythm desynchronization in response to movement
      observation is impaired in Parkinson's disease. METHOD: In a pilot study with
      nine patients with Parkinson's disease at a Hoehn and Yahr stage of I or II and
      eleven age-matched controls, we tested this hypothesis by comparing the event
      related desynchronization (ERD) patterns from the EEG recorded during the
      observation of hand action and baseline videos. RESULTS: Healthy subjects showed
      normal bilateral ERD of the mu-rhythm. In patients with Parkinson's disease this
      distinct ERD pattern was lacking. CONCLUSION: The results of this study suggest
      that event-related mu-rhythm desynchronization is impaired in Parkinson's
      disease, even at early stages of the disease. SIGNIFICANCE: Studying event
      related mu-rhythm desynchronization dysfunction in Parkinson's disease patients
      may enhance our understanding of symptoms as impaired motor learning.

PMID- 24560132
TI  - Automatic interpretation and writing report of the adult waking
      electroencephalogram.
AB  - Automatic interpretation of the EEG has so far been faced with significant
      difficulties because of a large amount of spatial as well as temporal information
      contained in the EEG, continuous fluctuation of the background activity depending
      on changes in the subject's vigilance and attention level, the occurrence of
      paroxysmal activities such as spikes and spike-and-slow-waves, contamination of
      the EEG with a variety of artefacts and the use of different recording electrodes
      and montages. Therefore, previous attempts of automatic EEG interpretation have
      been focussed only on a specific EEG feature such as paroxysmal abnormalities,
      delta waves, sleep stages and artefact detection. As a result of a long-standing
      cooperation between clinical neurophysiologists and system engineers, we report
      for the first time on a comprehensive, computer-assisted, automatic
      interpretation of the adult waking EEG. This system analyses the background
      activity, intermittent abnormalities, artefacts and the level of vigilance and
      attention of the subject, and automatically presents its report in written form.
      Besides, it also detects paroxysmal abnormalities and evaluates the effects of
      intermittent photic stimulation and hyperventilation on the EEG. This system of
      automatic EEG interpretation was formed by adopting the strategy that the
      qualified EEGers employ for the systematic visual inspection. This system can be
      used as a supplementary tool for the EEGer's visual inspection, and for educating
      EEG trainees and EEG technicians. 

PMID- 24560134
TI  - EEG biomarkers of NeuroAIDS.

PMID- 24560133
TI  - A mechanistic model of mismatch negativity in the ageing brain.
AB  - OBJECTIVE: We investigated the neurophysiological mechanisms underpinning the
      generation of the mismatch negativity (MMN) in the ageing brain. METHODS: We used
      dynamic causal modelling (DCM) to study connectivity models for healthy young and
      old subjects. MMN was elicited with an auditory odd-ball paradigm in two groups
      of healthy subjects with mean age 74 (n=30) and 26 (n=26). DCM was implemented
      using up to five cortical nodes. We tested models with different hierarchical
      complexities. RESULTS: We showed that the network generating MMN consisted of 5
      nodes that could modulate all intra- and inter-nodal connections. The inversion
      of this model showed that old subjects had increased input from rSTG to the rIFG
      (p<0.01) together with increased inhibition of pyramidal cells (p<0.05).
      Furthermore, there was reduced modulation of activity within rIFG (p<0.02) on
      stimulus change. CONCLUSION: The age related change in MMN is due to a decline in
      frontal-based control mechanisms, with alterations in connectivity between
      temporal and frontal regions together with a dysregulation of the excitatory
      inhibitory balance in the rIFG. SIGNIFICANCE: This study provides for the first
      time a neurobiological explanation for the age related changes of the MMN in the
      ageing brain.

PMID- 24560135
TI  - The peroxisome proliferator-activated receptor alpha agonist fenofibrate has no
      effect on insulin sensitivity compared to atorvastatin in type 2 diabetes
      mellitus; a randomised, double-blind controlled trial.
AB  - AIMS: Assess insulin sensitivity after treatment with a selective PPAR-alpha
      agonist compared to an HMG CoA reductase inhibitor in human subjects with type 2
      diabetes mellitus. METHODS: Thirteen subjects with Type 2 diabetes mellitus were
      studied in a double-blind crossover design with 4-week placebo run-in and washout
      and 12-week treatment periods, randomised to micronised fenofibrate 267 mg or
      atorvastatin 10mg daily followed by the alternate drug in the second period.
      Insulin resistance was measured using the isoglycaemic hyperinsulinaemic clamp
      method with isotope dilution. RESULTS: Weight, physical activity and other
      medications did not change. Total cholesterol (mean +/- standard error) was
      4.60+/-0.21 versus 3.9+/-0.22 mmol/L after fenofibrate and atorvastatin
      respectively, p<0.05. LDL was 2.70+/-0.19 versus 1.95+/-0.23 mmol/L, p<0.05 and
      triglyceride 1.64+/-0.23 versus 1.84+/-0.26 mmol/L, p<0.05. Insulin-stimulated
      whole-body glucose disposal (35.4+/-3.1 versus 33.2+/-3.0 MUmol/kg/min) and nadir
      endogenous glucose production (6.2+/-1.4 versus 7.0+/-1.1 MUmol/kg/min) revealed
      no significant differences in effects of the treatments. CONCLUSIONS: In human
      subjects with Type 2 diabetes mellitus there were characteristic differences in
      lipid profile changes but no difference in insulin sensitivity after treatment
      with micronised fenofibrate compared to atorvastatin. This study finds no
      evidence of increased insulin sensitivity using this selective PPAR-alpha agonist
      over a commonly used statin at these doses.

PMID- 24560137
TI  - Prevalence and predictors of anemia in a population of North Indian children.
AB  - OBJECTIVE: Anemia is an important health concern worldwide, particularly in poor
      populations such as in India. The objective of this study was to determine the
      prevalence and predictors of anemia and iron status. METHODS: One thousand
      children ages 6 to 30 mo were included in a study undertaken in low- to middle
      income neighborhoods in New Delhi, India. Children of Tigri and Dakshinpuri were
      identified through a community survey. Plasma concentrations of hemoglobin (Hb),
      soluble transferrin receptor (sTfR), folate, vitamin B12, and total homocysteine
      (tHcy) were measured. Predictors for plasma Hb concentration were identified in
      multiple linear regression models and considered significant if P-value <0.05.
      RESULTS: The prevalence of anemia (Hb concentration <11 g/dL) was 69.6% (n = 696)
      whereas the prevalence of iron deficiency (elevated sTfR i.e., >4.7 nmol/L) was
      31% (n = 309). The main predictors for Hb concentration were plasma
      concentrations of sTfR (standardized beta coefficient [beta], -0.49; P < 0.001),
      folate (beta, 0.15; P < 0.001), vitamin B12 (beta, 0.10; P < 0.001), tHcy (beta, 
      0.11; P < 0.001) among the biomarkers. Length-for-age Z score (beta, 0.08; P =
      0.002) and family income (beta, 0.06; P = 0.027) also predicted Hb concentration.
      CONCLUSION: Anemia was common in this population. Iron, folate, and vitamin B12
      status were important predictors for plasma Hb concentration. Improving the
      status of these nutrients might reduce the burden of childhood anemia in India.

PMID- 24560138
TI  - Markov modeling of ion channels: implications for understanding disease.
AB  - Ion channels are the bridge between the biochemical and electrical domains of our
      life. These membrane crossing proteins use the electric energy stored in
      transmembrane ion gradients, which are produced by biochemical activity to
      generate ionic currents. Each ion channel can be imagined as a small power plant
      similar to a hydroelectric power station, in which potential energy is converted
      into electric current. This current drives basically all physiological mechanisms
      of our body. It is clear that a functional blueprint of these amazing cellular
      power plants is essential for understanding the principle of all aspects of
      physiology, particularly neurophysiology. The golden path toward this blueprint
      starts with the biophysical investigation of ion channel activity and continues
      through detailed numerical modeling of these channels that will eventually lead
      to a full system-level description of cellular and organ physiology. Here, we
      discuss the first two stages of this process focusing on voltage-gated channels,
      particularly the voltage-gated sodium channel which is neurologically and
      pathologically important. We first detail the correlations between the known
      structure of the channel and its activity and describe some pathologies. We then
      provide a hands-on description of Markov modeling for voltage-gated channels.
      These two sections of the chapter highlight the dichotomy between the vast
      amounts of electrophysiological data available on voltage-gated channels and the
      relatively meager number of physiologically relevant models for these channels. 

PMID- 24560136
TI  - Down-regulation of miR-34a alleviates mesangial proliferation in vitro and
      glomerular hypertrophy in early diabetic nephropathy mice by targeting GAS1.
AB  - AIMS: Diabetic nephropathy (DN) is a major diabetic complication characterized by
      mesangial proliferation and glomerular hypertrophy. MicroRNAs might play an
      important role in these pathological processes. The aim of this study is to
      examine the possible association of miR-34a as one of the microRNAs with DN and
      underlying mechanisms in vitro and in vivo. METHODS: According to previous
      results of microarray which compared the different microRNAs between diabetic and
      normal control mice, miR-34a was chosen and its expression was detected by qRT
      PCR. Cell viability was then assessed using Cell Counting Kit-8 (CCK8) and 5
      ethynyl-20-deoxyuridine (EDU) incorporation. Antagomir was injected in db/db mice
      to down regulate miR-34a. Average diameter of glomeruli was analyzed by periodic
      acid-Schiff (PAS) stain of kidney. Luciferase gene report assay was then
      performed to identify the target gene of miR-34a. Additional immunoblotting and
      immunohistochemical analyses were implemented to verify the expression level of
      growth arrest-specific 1 (GAS1). RESULTS: MiR-34a expression level was increased
      under high glucose condition in vitro and in vivo. Down-regulation of miR-34a
      inhibits mice mesangial cells (MMCs) proliferation in vitro and alleviates
      glomerular hypertrophy in vivo. GAS1 was proved to be the target of miR-34a
      through luciferase report. Moreover, up-regulation of GAS1 expression was
      observed in the presence of miR-34a antagomir as compared with miR-34a antagomir
      NC in high-glucose-treated MMCs and db/db mice, respectively. CONCLUSIONS: MiR
      34a regulated mesangial proliferation and glomerular hypertrophy by directly
      inhibiting GAS1 in early DN.

PMID- 24560139
TI  - Ionic mechanisms in peripheral pain.
AB  - Chronic pain constitutes an important and growing problem in society with large
      unmet needs with respect to treatment and clear implications for quality of life.
      Computational modeling is used to complement experimental studies to elucidate
      mechanisms involved in pain states. Models representing the peripheral nerve
      ending often address questions related to sensitization or reduction in pain
      detection threshold. In models of the axon or the cell body of the unmyelinated C
      fiber, a large body of work concerns the role of particular sodium channels and
      mutations of these. Furthermore, in central structures: spinal cord or higher
      structures, sensitization often refers not only to enhanced synaptic efficacy but
      also to elevated intrinsic neuronal excitability. One of the recent developments
      in computational neuroscience is the emergence of computational
      neuropharmacology. In this area, computational modeling is used to study
      mechanisms of pathology with the objective of finding the means of restoring
      healthy function. This research has received increased attention from the
      pharmaceutical industry as ion channels have gained increased interest as drug
      targets. Computational modeling has several advantages, notably the ability to
      provide mechanistic links between molecular and cellular levels on the one hand
      and functions at the systems level on the other hand. These characteristics make
      computational modeling an additional tool to be used in the process of selecting
      pharmaceutical targets. Furthermore, large-scale simulations can provide a
      framework to systematically study the effects of several interacting disease
      parameters or effects from combinations of drugs. 

PMID- 24560141
TI  - The role of IP3 receptor channel clustering in Ca2+ wave propagation during
      oocyte maturation.
AB  - During oocyte maturation, the calcium-signaling machinery undergoes a dramatic
      remodeling resulting in distinctly different calcium-release patterns on all
      organizational scales from puffs to waves. The dynamics of the Ca(2+) release
      wave in mature as compared to immature oocytes are defined by a slower
      propagation speed and longer duration of the high Ca(2+) plateau. In this
      chapter, we use computational modeling to identify the changes in the signaling
      machinery, which contribute most significantly to the alterations observed in
      Ca(2+) wave propagation during Xenopus oocyte maturation. In addition to loss of
      store-operated calcium entry and internalization of plasma membrane pumps, we
      propose that spatial reorganization of the IP3 receptors in the plane of the ER
      membrane is a key factor for the observed signaling changes in Ca(2+) wave
      propagation. 

PMID- 24560140
TI  - Implications of cellular models of dopamine neurons for schizophrenia.
AB  - Midbrain dopamine neurons are pacemakers in vitro, but in vivo they fire less
      regularly and occasionally in bursts that can lead to a temporary cessation in
      firing produced by depolarization block. The therapeutic efficacy of
      antipsychotic drugs used to treat the positive symptoms of schizophrenia has been
      attributed to their ability to induce depolarization block within a subpopulation
      of dopamine neurons. We summarize the results of experiments characterizing the
      physiological mechanisms underlying the ability of these neurons to enter
      depolarization block in vitro, and our computational simulations of those
      experiments. We suggest that the inactivation of voltage-dependent Na(+)
      channels, and, in particular, the slower component of this inactivation, is
      critical in controlling entry into depolarization block. In addition, an ether-a
      go-related gene (ERG) K(+) current also appears to be involved by delaying entry
      into and speeding recovery from depolarization block. Since many antipsychotic
      drugs share the ability to block this current, ERG channels may contribute to the
      therapeutic effects of these drugs. 

PMID- 24560142
TI  - Modeling mitochondrial function and its role in disease.
AB  - Many neurodegenerative diseases involve defects in mitochondrial function. These
      defects often arise from mutations carried in the genes that code mitochondrial
      proteins. Many of these defective proteins are involved in mitochondrial energy
      metabolism which is one of the primary roles of the mitochondria. However, others
      proteins have other roles that are related to signaling or mitochondrial
      structure. The interaction of the mitochondrial proteins is complex.
      Understanding these complex dynamics requires the use of computational models.
      Studies have started to exploit such models, but much further work is necessary
      to understand mitochondrial function and its role in neurodegenerative disease. 

PMID- 24560143
TI  - Mathematical modeling of neuronal polarization during development.
AB  - During development of the brain, morphogenesis of neurons is dynamically
      organized from a simple rounded shape to a highly polarized morphology consisting
      of soma, one axon, and dendrites, which is a basis for establishing the
      unidirectional transfer of electric signals between neurons. The mechanism of
      such polarization is thought to be "local activation-global inhibition"; however,
      globally diffusing inhibitor molecules have not been identified. In this chapter,
      we present a theoretical modeling approach of such neuronal development. We first
      summarize biological research on neuronal polarization and then develop a
      biophysical model. Through mathematical analysis, principles of local activation
      global inhibition are illustrated based on active transport, protein degradation,
      and neurite growth, but not on globally diffusing inhibitor. 

PMID- 24560145
TI  - Computational modeling of diffusion in the cerebellum.
AB  - Diffusion is a major transport mechanism in living organisms. In the cerebellum,
      diffusion is responsible for the propagation of molecular signaling involved in
      synaptic plasticity and metabolism, both intracellularly and extracellularly. In
      this chapter, we present an overview of the cerebellar structure and function. We
      then discuss the types of diffusion processes present in the cerebellum and their
      biological importance. We particularly emphasize the differences between
      extracellular and intracellular diffusion and the presence of tortuosity and
      anomalous diffusion in different parts of the cerebellar cortex. We provide a
      mathematical introduction to diffusion and a conceptual overview of various
      computational modeling techniques. We discuss their scope and their limit of
      application. Although our focus is the cerebellum, we have aimed at presenting
      the biological and mathematical foundations as general as possible to be
      applicable to any other area in biology in which diffusion is of importance. 

PMID- 24560144
TI  - Multiscale modeling of cell shape from the actin cytoskeleton.
AB  - The actin cytoskeleton is a dynamic structure that constantly undergoes complex
      reorganization events during many cellular processes. Mathematical models and
      simulations are powerful tools that can provide insight into the physical
      mechanisms underlying these processes and make predictions that can be
      experimentally tested. Representation of the interactions of the actin filaments
      with the plasma membrane and the movement of the plasma membrane for computation
      remains a challenge. Here, we provide an overview of the different modeling
      approaches used to study cytoskeletal dynamics and highlight the differential
      geometry approach that we have used to implement the interactions between the
      plasma membrane and the cytoskeleton. Using cell spreading as an example, we
      demonstrate how this approach is able to successfully capture in simulations,
      experimentally observed behavior. We provide a perspective on how the
      differential geometry approach can be used for other biological processes. 

PMID- 24560146
TI  - Astrocyte-neuron interactions: from experimental research-based models to
      translational medicine.
AB  - In this chapter, we review the principal astrocyte functions and the interactions
      between neurons and astrocytes. We then address how the experimentally observed
      functions have been verified in computational models and review recent
      experimental literature on astrocyte-neuron interactions. Benefits of
      computational neuroscience work are highlighted through selected studies with
      neurons and astrocytes by analyzing the existing models qualitatively and
      assessing the relevance of these models to experimental data. Common strategies
      to mathematical modeling and computer simulation in neuroscience are summarized
      for the nontechnical reader. The astrocyte-neuron interactions are then further
      illustrated by examples of some neurological and neurodegenerative diseases,
      where the miscommunication between glia and neurons is found to be increasingly
      important. 

PMID- 24560147
TI  - Dynamic metabolic control of an ion channel.
AB  - G-protein-coupled receptors mediate responses to external stimuli in various cell
      types. We are interested in the modulation of KCNQ2/3 potassium channels by the
      Gq-coupled M1 muscarinic (acetylcholine) receptor (M1R). Here, we describe
      development of a mathematical model that incorporates all known steps along the
      M1R signaling cascade and accurately reproduces the macroscopic behavior we
      observe when KCNQ2/3 currents are inhibited following M1R activation. Gq protein
      coupled receptors of the plasma membrane activate phospholipase C (PLC) which
      cleaves the minor plasma membrane lipid phosphatidylinositol 4,5-bisphosphate
      (PI(4,5)P2) into the second messengers diacylgycerol and inositol 1,4,5
      trisphosphate, leading to calcium release, protein kinase C (PKC) activation, and
      PI(4,5)P2 depletion. Combining optical and electrical techniques with knowledge
      of relative abundance of each signaling component has allowed us to develop a
      kinetic model and determine that (i) M1R activation and M1R/Gbeta interaction are
      fast; (ii) Galphaq/Gbeta separation and Galphaq/PLC interaction have intermediate
      time constants; (iii) the amount of activated PLC limits the rate of KCNQ2/3
      suppression; (iv) weak PLC activation can elicit robust calcium signals without
      net PI(4,5)P2 depletion or KCNQ2/3 channel inhibition; and (v) depletion of
      PI(4,5)P2, and not calcium/CaM or PKC-mediated phosphorylation, closes KCNQ2/3
      potassium channels, thereby increasing neuronal excitability. 

PMID- 24560148
TI  - Modeling molecular pathways of neuronal ischemia.
AB  - Neuronal ischemia, the consequence of a stroke (cerebrovascular accident), is a
      condition of reduced delivery of nutrients to brain neurons. The brain consumes
      more energy per gram of tissue than any other organ, making continuous blood flow
      critical. Loss of nutrients, most critically glucose and O2, triggers a large
      number of interacting molecular pathways in neurons and astrocytes. The dynamics
      of these pathways take place over multiple temporal scales and occur in multiple
      interacting cytosolic and organelle compartments: in mitochondria, endoplasmic
      reticulum, and nucleus. The complexity of these relationships suggests the use of
      computer simulation to understand the interplay between pathways leading to
      reversible or irreversible damage, the forms of damage, and interventions that
      could reduce damage at different stages of stroke. We describe a number of models
      and simulation methods that can be used to further our understanding of ischemia.

PMID- 24560151
TI  - Multiscale modeling and synaptic plasticity.
AB  - Synaptic plasticity is a major convergence point for theory and computation, and
      the process of plasticity engages physiology, cell, and molecular biology. In its
      many manifestations, plasticity is at the hub of basic neuroscience questions
      about memory and development, as well as more medically themed questions of
      neural damage and recovery. As an important cellular locus of memory, synaptic
      plasticity has received a huge amount of experimental and theoretical attention.
      If computational models have tended to pick specific aspects of plasticity, such
      as STDP, and reduce them to an equation, some experimental studies are equally
      guilty of oversimplification each time they identify a new molecule and declare
      it to be the last word in plasticity and learning. Multiscale modeling begins
      with the acknowledgment that synaptic function spans many levels of signaling,
      and these are so tightly coupled that we risk losing essential features of
      plasticity if we focus exclusively on any one level. Despite the technical
      challenges and gaps in data for model specification, an increasing number of
      multiscale modeling studies have taken on key questions in plasticity. These have
      provided new insights, but importantly, they have opened new avenues for
      questioning. This review discusses a wide range of multiscale models in
      plasticity, including their technical landscape and their implications. 

PMID- 24560152
TI  - Preface. Computational neuroscience.

PMID- 24560149
TI  - Modeling intracellular signaling underlying striatal function in health and
      disease.
AB  - Striatum, which is the input nucleus of the basal ganglia, integrates cortical
      and thalamic glutamatergic inputs with dopaminergic afferents from the substantia
      nigra pars compacta. The combination of dopamine and glutamate strongly modulates
      molecular and cellular properties of striatal neurons and the strength of
      corticostriatal synapses. These actions are performed via intracellular signaling
      networks, containing several intertwined feedback loops. Understanding the role
      of dopamine and other neuromodulators requires the development of quantitative
      dynamical models for describing the intracellular signaling, in order to provide
      precise unambiguous descriptions and quantitative predictions. Building such
      models requires integration of data from multiple data sources containing
      information regarding the molecular interactions, the strength of these
      interactions, and the subcellular localization of the molecules. Due to the
      uncertainty, variability, and sparseness of these data, parameter estimation
      techniques are critical for inferring or constraining the unknown parameters, and
      sensitivity analysis evaluates which parameters are most critical for a given
      observed macroscopic behavior. Here, we briefly review the modeling approaches
      and tools that have been used to investigate biochemical signaling in the
      striatum, along with some of the models built around striatum. We also suggest a
      future direction for the development of such models from the, now becoming
      abundant, high-throughput data. 

PMID- 24560150
TI  - Data-driven modeling of synaptic transmission and integration.
AB  - In this chapter, we describe how to create mathematical models of synaptic
      transmission and integration. We start with a brief synopsis of the experimental
      evidence underlying our current understanding of synaptic transmission. We then
      describe synaptic transmission at a particular glutamatergic synapse in the
      mammalian cerebellum, the mossy fiber to granule cell synapse, since data from
      this well-characterized synapse can provide a benchmark comparison for how well
      synaptic properties are captured by different mathematical models. This chapter
      is structured by first presenting the simplest mathematical description of an
      average synaptic conductance waveform and then introducing methods for
      incorporating more complex synaptic properties such as nonlinear voltage
      dependence of ionotropic receptors, short-term plasticity, and stochastic
      fluctuations. We restrict our focus to excitatory synaptic transmission, but most
      of the modeling approaches discussed here can be equally applied to inhibitory
      synapses. Our data-driven approach will be of interest to those wishing to model
      synaptic transmission and network behavior in health and disease. 

PMID- 24560153
TI  - World Kidney Day 2014: CKD and the aging population.

PMID- 24560154
TI  - Albuminuria: time to focus on accuracy.

PMID- 24560155
TI  - Drug prescribing in kidney disease: can't we do better?

PMID- 24560156
TI  - Arteriovenous fistula patency: some answers but questions remain.

PMID- 24560158
TI  - The KDOQI US commentary on KDIGO anemia guideline and quality of life.

PMID- 24560157
TI  - Urinary lithogenic risk profile in recurrent stone formers with hyperoxaluria: a
      randomized controlled trial comparing DASH (Dietary Approaches to Stop
      Hypertension)-style and low-oxalate diets.
AB  - BACKGROUND: Patients with nephrolithiasis and hyperoxaluria generally are advised
      to follow a low-oxalate diet. However, most people do not eat isolated nutrients,
      but meals consisting of a variety of foods with complex combinations of
      nutrients. A more rational approach to nephrolithiasis prevention would be to
      base dietary advice on the cumulative effects of foods and different dietary
      patterns rather than single nutrients. STUDY DESIGN: Randomized controlled trial.
      SETTING & PARTICIPANTS: Recurrent stone formers with hyperoxaluria (urine oxalate
      > 40 mg/d). INTERVENTION: The intervention group was asked to follow a calorie
      controlled Dietary Approaches to Stop Hypertension (DASH)-style diet (a diet high
      in fruit, vegetables, whole grains, and low-fat dairy products and low in
      saturated fat, total fat, cholesterol, refined grains, sweets, and meat), whereas
      the control group was prescribed a low-oxalate diet. Study length was 8 weeks.
      OUTCOMES: Primary: change in urinary calcium oxalate supersaturation. SECONDARY:
      Changes in 24-hour urinary composition. RESULTS: 57 participants were randomly
      assigned (DASH group, 29; low-oxalate group, 28). 41 participants completed the
      trial (DASH group, 21; low-oxalate group, 20). As-treated analysis showed a trend
      for urinary oxalate excretion to increase in the DASH versus the low-oxalate
      group (point estimate of difference, 9.0mg/d; 95% CI, -1.1 to 19.1mg/d; P=0.08).
      However, there was a trend for calcium oxalate supersaturation to decrease in the
      DASH versus the low-oxalate group (point estimate of difference, -1.24; 95% CI, 
      2.80 to 0.32; P=0.08) in association with an increase in magnesium and citrate
      excretion and urine pH in the DASH versus low-oxalate group. LIMITATIONS: Limited
      sample size, as-treated analysis, nonsignificant results. CONCLUSIONS: The DASH
      diet might be an effective alternative to the low-oxalate diet in reducing
      calcium oxalate supersaturation and should be studied more.

PMID- 24560159
TI  - Intravenous iron dose and frequency determine infection risks.

PMID- 24560160
TI  - Zero dark thirty: a nephrologist at the movies.

PMID- 24560161
TI  - Quiz page March 2014: A patient with malignant hypertension, thrombotic
      microangiopathy, and nephrotic-range proteinuria.

PMID- 24560162
TI  - Binding versus triggering riboswitches.
AB  - In this issue of Chemistry & Biology, Trausch and Batey report a discrepancy
      between ligand binding affinity and the effect of transcription termination in a
      THF riboswitch, raising some important questions about our current understanding
      of ligand-dependent RNA switches. 

PMID- 24560163
TI  - How to break the rules of dioxygen activation.
AB  - In this issue of Chemistry & Biology, Thierbach and colleagues establish the
      chemical mechanism for a cofactor-independent dioxygenase enzyme, a member of a
      small group of enzymes that can activate dioxygen without requiring a metal ion
      or redox cofactor. 

PMID- 24560164
TI  - Phenotypic directed antibody selection.
AB  - In this issue of Chemistry & Biology, Xie and colleagues describe a "phenotype
      directed" approach to identify antibodies that protect cells from death caused by
      rhinovirus infection. The cellular antibody library of 10(8) clones yielded two
      antibodies that prevented cell death via the same viral target: rhinovirus 3C
      protease. 

PMID- 24560165
TI  - Dynamic prions revealed by magic.
AB  - Prion proteins can be propagated as amyloid fibrils with several different
      conformational variants. By providing structural information at atomic level for
      two such variants of a yeast prion, Frederick and colleagues, in this issue of
      Chemistry & Biology, reveal how conformational flexibility can generate
      phenotypic diversity. 

PMID- 24560167
TI  - Subtypes of potentially inappropriate medications in older Chinese-Americans
      during care transitions: cross sectional retrospective study.
AB  - BACKGROUND: The number of Chinese Americans is growing and nearly 20% of older
      Chinese-American home care patients have at least one potentially inappropriate
      medications (PIMs) prescribed at hospital discharge. Further examination of PIMs
      during care transition is warranted, especially among older Chinese-Americans.
      OBJECTIVES: To describe, during care transitions from hospital to home care: (i)
      the subtypes of PIMs, (ii) the difference of PIM prevalence prescribed at
      hospital discharge as compared to home care admission, (iii) the relationship
      between subtypes of PIMs, and (iv) issues affecting medication reconciliation
      among older Chinese-Americans. METHODS: This cross-sectional, retrospective study
      was conducted in a large urban home care agency from June 2010 to July 2011. From
      data collected by in-home survey and chart abstraction, PIMs were identified
      using 2002 diagnosis-independent Beers criteria. The difference of PIM prevalence
      at hospital discharge and at home care admission was analyzed by Wilcoxon Signed
      Ranks test. The relationship between subtypes of PIMs was evaluated using Phi
      coefficient. PARTICIPANTS: 82 older (age 65 years and above) Chinese-American
      home care patients following recent hospital discharge. RESULTS: 3.38% (22) and
      another 3.72% (28) of prescribed medications were identified as PIMs at hospital
      discharge and home care admission, respectively. There was no statistically
      significant difference in PIM prevalence identified at hospital discharge and at
      homecare admission (z=-1.732, p=.083). PIMs included: long-term use of stimulant
      laxatives and high-dosages of ferrous sulfate, and a significant relationship
      between these two PIMS (r=.224, p=.04). More than 80% (n=65) of study
      participants reported low education levels and limited English proficiency.
      CONCLUSIONS: Subtypes of PIMs were ordered during the post-hospital transfers,
      indicating the necessity to review the appropriateness of medications during this
      transition. Guidelines such as Beer's criteria regarding appropriateness of
      medications should be incorporated in medication reconciliation before adding new
      medications to treat the older adult's health problems. The medication management
      process needs to be both culturally sensitive and adapted to literacy level;
      validating the patients' full understanding of their medications is paramount.

PMID- 24560166
TI  - Blood transfusion practices in dialysis patients in a dynamic regulatory
      environment.
AB  - BACKGROUND: In 2011, Medicare implemented a prospective payment system (PPS)
      covering an expanded bundle of services that excluded blood transfusions. This
      led to concern about inappropriate substitution of transfusions for other anemia
      management methods. STUDY DESIGN: Medicare claims were used to calculate
      transfusion rates among dialysis patients pre- and post-PPS. Linear probability
      regressions adjusted transfusion trends for patient characteristics. SETTING &
      PARTICIPANTS: Dialysis patients for whom Medicare was the primary payer between
      2008 and 2012. PREDICTOR: Pre-PPS (2008-2010) versus post-PPS (2011-2012).
      OUTCOMES & MEASUREMENTS: Monthly and annual probability of receiving one or more
      blood transfusions. RESULTS: Monthly rates of one or more transfusions varied
      from 3.8%-4.8% and tended to be lowest in 2010. Annual rates of transfusion
      events per patient were -10% higher in relative terms post-PPS, but the absolute
      magnitude of the increase was modest (-0.05 events/patient). A larger proportion
      received 4 or more transfusions (3.3% in 2011 and 2012 vs 2.7%-2.8% in prior
      years). Controlling for patient characteristics, the monthly probability of
      receiving a transfusion was significantly higher post-PPS (beta = 0.0034; P <
      0.001), representing an -7% relative increase. Transfusions were more likely for
      females and patients with more comorbid conditions and less likely for blacks
      both pre- and post-PPS. LIMITATIONS: Possible underidentification of transfusions
      in the Medicare claims, particularly in the inpatient setting. Also, we do not
      observe which patients might be appropriate candidates for kidney
      transplantation. CONCLUSIONS: Transfusion rates increased post-PPS, but these
      increases were modest in both absolute and relative terms. The largest increase
      occurred for patients already receiving several transfusions. Although these
      findings may reduce concerns regarding the impact of Medicare's PPS on
      inappropriate transfusions that impair access to kidney transplantation or stress
      blood bank resources, transfusions should continue to be monitored.

PMID- 24560168
TI  - Different hip rotations influence hip abductor muscles activity during isometric
      side-lying hip abduction in subjects with gluteus medius weakness.
AB  - The purpose of this study was to establish the effects of different hip rotations
      during isometric side-lying hip abduction (SHA) in subjects with gluteus medius
      (Gmed) weakness by investigating the electromyographic (EMG) amplitude of the
      Gmed, tensor fasciae latae (TFL) activity, and gluteus maximus (Gmax), and the
      activity ratio of the Gmed/TFL, Gmax/TFL, and Gmed/Gmax. Nineteen subjects with
      Gmed weakness were recruited for this study. Subjects performed three isometric
      hip abductions: frontal SHA with neutral hips (SHA-N), frontal SHA with hip
      medial rotation (SHA-MR), and frontal SHA with hip lateral rotation (SHA-LR).
      Surface EMG amplitude was measured to collect the EMG data from the Gmed, TFL,
      and Gmax. A one-way repeated-measures analysis of variance was used to determine
      the statistical significance of the Gmed, TFL, and Gmax EMG activity and the
      Gmed/TFL, Gmax/TFL, and Gmed/Gmax EMG activity ratios. Gmed EMG activity was
      significantly greater in SHA-MR than in SHA-N. TFL EMG activity was significantly
      greater in SHA-LR than in SHA-N. The Gmed/TFL and Gmed/Gmax EMG activity ratios
      were also significantly greater in SHA-MR than in SHA-N or SHA-LR. The results of
      this study suggest that SHA-MR can be used as an effective method to increase
      Gmed activation and to decrease TFL activity during SHA exercises. 

PMID- 24560169
TI  - Up-titration of allopurinol in patients with gout.
AB  - OBJECTIVES: European League against Rheumatism (EULAR) gout management guidelines
      recommend achieving a target urate level <6.0 mg/dL (<357 umol/L). Allopurinol is
      the most widely used urate-lowering therapy; however, many gout patients who are
      prescribed allopurinol do not have urate levels optimally controlled. The
      objective of this analysis was to review the efficacy and tolerability of
      allopurinol up-titration in achieving the EULAR target levels. METHOD: The
      Febuxostat versus Allopurinol Streamlined Trial (FAST) is an ongoing multi-centre
      study comparing the cardiovascular safety of febuxostat and allopurinol (target
      recruitment: 5706 patients). Recruited patients were already taking allopurinol
      and the protocol required up-titration of daily allopurinol dose, in 100 mg
      increments, to achieve the EULAR urate target level prior to randomisation. We
      reviewed pre-randomisation data from the first 400 recruited and subsequently
      randomised FAST patients. RESULTS: Of 400 patients, 144 (36%) had urate levels
      >=357 umol/L at screening and required allopurinol up-titration. Higher urate
      levels were significantly associated with lower allopurinol dose, male sex,
      increased BMI, increased alcohol intake and diuretic use. Mean fall in urate
      levels after a single 100-mg dose increase was 71 umol/L. The number of up
      titrations required ranged from one to five (median = 1) with 65% of patients
      controlled after one 100-mg up-titration. Overall, 97% of up-titrated patients
      achieved target urate levels with median final allopurinol dose of 300 mg daily.
      Side effects and complications of up-titration were minimal. CONCLUSION: Overall,
      36% of FAST patients were not at target urate levels and required up-titration.
      Allopurinol up-titration was effective in achieving urate target levels and was
      generally well tolerated by patients.

PMID- 24560170
TI  - Recommendations for the management of cardiovascular risk in patients with
      rheumatoid arthritis: scientific evidence and expert opinion.
AB  - OBJECTIVES: Last recommendations regarding cardiovascular risk (CVR) in
      rheumatoid arthritis (RA) patients were developed by the EULAR group in 2010. The
      aim is to update evidence-based recommendations about this worrying health
      problem. METHODS: We assembled a multidisciplinary workgroup (rheumatologists,
      endocrinologist, cardiologist, and epidemiologist) and a panel of 28 expert
      rheumatologists. The study was carried out in two big phases: identifying key
      areas in the prevention and management of CVR and developing a set of
      recommendations based on a review of the available scientific evidence and use of
      the Delphi consensus technique. All this has been developed according to an
      updating process of evidence-based recommendations. RESULTS: Overall, 25
      recommendations were made addressing three complementary areas: CVR assessment
      tools, patient eligibility for assessment, and treatment strategies for control
      of CVR. The grade of the recommendations was not substantially modified compared
      to the original EULAR recommendations, except in two of them, which were upgraded
      from C to B. These two recommendations are the ones related to the use of
      corticosteroids and smoking cessation. The new developed recommendations address
      these two areas: CVR assessment and treatment strategies for control of CVR.
      CONCLUSIONS: There are substantial gaps in the current knowledge that do not
      allow classifying properly RA patients based on their actual CVR and to
      accurately identify those patients who would benefit from CVR assessment.
      Consequently, studies designed to determine the causal effects of RA disease
      characteristics on cardiovascular morbidity/mortality and to identify patients at
      high risk of cardiovascular disease are still needed.

PMID- 24560171
TI  - Co-chaperones of Hsp90 in Plasmodium falciparum and their concerted roles in
      cellular regulation.
AB  - Co-chaperones are well-known regulators of heat shock protein 90 (Hsp90). Hsp90
      is a molecular chaperone that is essential in the eukaryotes for the folding and
      activation of numerous proteins involved in important cellular processes such as
      signal transduction, growth and developmental regulation. Co-chaperones assist
      Hsp90 in the protein folding process by modulating conformational changes to
      promote client protein interaction and functional maturation. With the
      recognition of Plasmodium falciparum Hsp90 (PfHsp90) as a potential antimalarial
      drug target, there is obvious interest in the study of its co-chaperones in their
      partnership in regulating cellular processes in malaria parasite. Previous
      studies on PfHsp90 have identified more than 10 co-chaperones in P. falciparum
      genome. However, many of them remained annotated as putative proteins as their
      functionality has not been validated experimentally. So far, only five co
      chaperones, PfHop, Pfp23, PfAha1, PfPP5 and PfFKBP35 have been characterized and
      shown to interact with PfHsp90. This review will summarize current knowledge on
      the co-chaperones in P. falciparum and discuss their regulatory roles on PfHsp90.
      As certain eukaryotic co-chaperones have also been implicated in altering the
      affinity of Hsp90 for its inhibitor, this review will also examine plasmodial co
      chaperones' potential influence on approaches towards designing antimalarials
      targeting PfHsp90.

PMID- 24560172
TI  - Effect of surgical repair of the joint capsule in mandibular condyle fractures in
      adult rats.
AB  - PURPOSE: The aim of the present study was to assess histologic changes in the
      temporomandibular joint (TMJ) of adult rats subjected to unilateral fracture of
      the mandibular condyle and soft tissue injury. MATERIALS AND METHODS: The animals
      were divided into 2 groups: one had surgical treatment for soft tissue repair and
      the other had no soft tissue treatment. All histologic evaluations were performed
      according to the presence or absence of synovitis, vascularity, presence or
      absence of joint inflammation, and presence or absence of the articular disc. The
      contralateral TMJs also were evaluated. RESULTS: The results showed few
      histologic changes in the synovial membrane and joint disc for the 2 groups and
      in the synovial membrane and disc of the contralateral side, where indirect
      trauma occurred in the unoperated joint. CONCLUSION: This study showed that
      treating or not treating soft tissues does not change the treatment results of
      condyle fracture or interfere with TMJ pathosis.

PMID- 24560173
TI  - Use of lincomycin-impregnated demineralized freeze-dried bone allograft in the
      periodontal defect after third molar surgery.
AB  - PURPOSE: The aim of the present study was to evaluate the periodontal
      regenerative capacity of demineralized freeze-dried bone allograft (DFDBA) alone
      or used with local lincomycin. MATERIALS AND METHODS: In the present single
      blind, randomized, controlled clinical trial, 20 subjects 26 years old or older,
      requiring extraction of bilateral third molars (M3s), were included. Each subject
      was randomly assigned to receive either DFDBA or DFDBA plus lincomycin therapy.
      Within the subjects, 1 M3 site was randomly selected to be the experimental site
      and the contralateral served as the control and was permitted to heal without
      intervention. The primary variables were changes in the probing depth (PD),
      clinical alveolar bone levels (ABLs), and radiographic alveolar bone density
      (ABD) on the distal aspect of second molar between baseline (immediately
      postoperatively) and 26 weeks postoperatively (T26). Appropriate sample sizes and
      descriptive, bivariate, and multivariate statistics were computed. RESULTS: For
      both treatment and control sites, between T0 and T26, statistically significant
      improvements were seen in the ABLs and ABD (P < .05). Within-subject comparisons
      showed no significant differences in PD, ABL, or ABD between the treatment and
      control M3 sites at T0 or T26 (P > .05). Also, no significant differences were
      found in the PD, ABL, or ABD between the 2 treatment M3 sites at T26 (P > .05).
      CONCLUSIONS: The results of the present study have revealed that the PD, ABL, and
      ABD improved after M3 removal in subjects 26 years old or older, irrespective of
      the treatment or control group. Reconstructive procedures (e.g., DFDBA with or
      without lincomycin therapy) did not offer predictable benefits compared with a no
      treatment protocol in patients younger than 30 years old.

PMID- 24560174
TI  - Squamous cell carcinoma of the pectoralis major myocutaneous flap donor site.
AB  - The pectoralis major myocutaneous flap is considered a workhorse flap in the
      reconstruction of head and neck defects after cancer ablative surgeries and
      remains one of the most widely used reconstructive options. Complications at the
      donor site after the use of this flap, although rare, do occur and are usually
      restricted to minor infections, hematoma, and seroma formation. Metastasis to the
      flap donor site is a rare complication with limited documentation. Metastasis at
      the donor site usually follows local recurrence at the primary site, supporting
      the probable hypothesis of re-establishment of lymphatic drainage to the primary
      site by the flap pedicle. Tumor implantation, although a probable cause for
      metastasis at the donor site, cannot be confidently distinguished from other
      mechanisms, such as hematogenous spread or lymphogenous metastasis. This report
      describes a case that supports a seeding or tumor implantation mechanism of
      metastasis exclusively. 

PMID- 24560175
TI  - Participative decentralization of diabetes care in Davao City (Philippines)
      according to the Chronic Care Model: a program evaluation.
AB  - AIM: To assess the effectiveness of the Diabetes Project in Davao City,
      Philippines, regarding diabetes care access, diabetes management and
      cardiovascular risk factors. The project was developed in accordance with the
      Chronic Care Model (CCM) framework. METHODS: A non-randomized cross-sectional
      survey was conducted in nine intervention and five control Barangays (villages).
      People with diabetes aged >=20 years were interviewed using a structured
      questionnaire; height, weight, waist circumference, and blood pressure were
      measured; HbA1c was tested with a NSGP-certified point-of-care device. Logistic
      regression models were used to compare the two groups. RESULTS: The intervention
      group (n=503) scored better than the controls (n=136) on the following (OR, 95%
      CI): percentage of patients taking metformin (1.5, 1.0-2.2); and in the last 12
      months: laboratory test for fasting blood sugar (1.6, 1.1-2.3), HbA1c (6.0, 2.4
      15.1), lipid profile (1.7, 1.1-2.5), nutritionist visit (1.6, 1.0-2.5) and
      therapeutic education session (2.7, 1.8-4.0). Glycemic control (HbA1c<7%) was
      also better in the intervention Barangays (1.6, 1.0-2.4). There were no
      statistical differences between the two groups for number of visits, and levels
      of other cardiovascular risk factors. CONCLUSIONS: Our findings support the
      effectiveness of implementing the CCM framework in a low-to-middle income country
      on glycemic control and diabetes management.

PMID- 24560176
TI  - Correlates of condom use among males in North Sudan.
AB  - Objectives In sub-Saharan Africa countries, HIV infections are transmitted
      primary through heterosexual contact. Correct and consistent condom use has been
      promoted as a method to prevent sexually transmissible infections, including HIV.
      The aim of this study was to assess and determine the factors influencing condom
      use in Khartoum, Sudan. MATERIALS AND METHODS: Out of the 45 voluntary
      counselling and testing centres in Khartoum region, 10 centres were selected. A
      random sample of 804 respondents aged 20-40 years was selected. Stepwise multiple
      logistic regression analysis was used to investigate the predictors of condom
      use. RESULTS: About 12% of respondents reported using condoms consistently, 41.5%
      used them sporadically and 46.3% were nonusers. Most of the participants had
      problems with condom use (81.9%) and friends were the main source of condoms
      (72%). Knowledge about AIDS transmission, knowing someone who is infected with or
      had died of AIDS, experiencing condom problems, type of sexual partners, purchase
      embarrassment and education were the main predictors of condom use. CONCLUSIONS:
      Condom use among the Sudanese is low. Strategies to promote condom use should
      focus on price support for condoms by the government, expanded private sector
      condom distribution and the integration of sex education in school curriculums or
      via frequent discussion on television.

PMID- 24560177
TI  - Neutral endopeptidase inhibitor versus angiotensin converting enzyme inhibitor in
      a rat model of the metabolic syndrome.
AB  - The antihypertensive treatment in patients with metabolic syndrome is unclear. We
      therefore used a rat model of the metabolic syndrome and compared the effects of
      enalapril, an angiotensin-converting-enzyme inhibitor, with candoxatril, a
      neutral endopeptidase inhibitor that inhibits degradation of atrial natriuretic
      peptide and, in addition to lowering blood pressure, exerts metabolically
      beneficial activity. Ten male Sprague Dawley rats were fed regular rat chow for 5
      weeks. Fifty male Sprague Dawley rats were fed a high-fructose diet for 3 weeks,
      followed by addition of enalapril, 10 mg/Kg/d, or candoxatril, 25, 50, or 100
      mg/Kg/d, for 2 weeks. Systolic blood pressure, plasma triglyceride level, and
      insulin level were measured at baseline and after 3 weeks and 5 weeks. Three
      weeks of a high-fructose diet led to a significant increase in all metabolic
      parameters. Candoxatril and enalapril lowered systolic blood pressure
      significantly (candoxatril -10 +/- 1 to -22 +/- 1 mm Hg and enalapril -27 +/- 2
      mm Hg). High-dose candoxatril and enalapril significantly decreased plasma
      triglyceride levels (by 17.8% and 32.8%, respectively), but only high-dose
      candoxatril decreased plasma insulin levels significantly (by 25.3%). High-dose
      candoxatril is a metabolically favorable option for lowering blood pressure in a
      rat model of metabolic syndrome. 

PMID- 24560178
TI  - [Health 2.0, blogs and journals].

PMID- 24560179
TI  - The effects of umbilical cord milking on hemodynamics and neonatal outcomes in
      premature neonates.
AB  - OBJECTIVE: To determine whether umbilical cord milking (UCM) improves systemic
      blood flow and reduces neonatal morbidities compared with immediate cord clamping
      (ICC). STUDY DESIGN: Women admitted to a tertiary care center and delivering
      before 32 weeks' gestation were randomized to receive UCM or ICC. Three blinded
      serial echocardiograms were performed in the first 2 days of the infant's life.
      The primary outcome was measured systemic blood flow (superior vena cava flow) at
      each time point. RESULTS: Of the 60 neonates who were enrolled and randomized, 30
      were assigned to cord milking and 30 to ICC. Neonates randomized to cord milking
      had greater measures of superior vena cava flow and right ventricular output in
      the first 6 hours and 30 hours of life. Neonates receiving UCM also had greater
      serum hemoglobin, received fewer blood transfusions, fewer days on oxygen
      therapy, and less frequent use of oxygen at 36 weeks' corrected postmenstrual
      age. CONCLUSIONS: We demonstrate greater systemic blood flow with UCM in preterm
      neonates compared with ICC. Future large prospective trials are needed to
      determine whether UCM reduces intraventricular hemorrhage and other long-term
      morbidities.

PMID- 24560180
TI  - Attitudes about domestic violence and the use of harsh discipline.

PMID- 24560181
TI  - Randomized controlled trial of oxygen saturation targets in very preterm infants:
      two year outcomes.
AB  - OBJECTIVE: To assess whether an oxygen saturation (Spo2) target of 85%-89%
      compared with 91%-95% reduced the incidence of the composite outcome of death or
      major disability at 2 years of age in infants born at <28 weeks' gestation. STUDY
      DESIGN: A total 340 infants were randomized to a lower or higher target from <24
      hours of age until 36 weeks' gestational age. Blinding was achieved by targeting
      a displayed Spo2 of 88%-92% using a saturation monitor offset by +/-3% within the
      range 85%-95%. True saturations were displayed outside this range. Follow-up at 2
      years' corrected age was by pediatric examination and formal neurodevelopmental
      assessment. Major disability was gross motor disability, cognitive or language
      delay, severe hearing loss, or blindness. RESULTS: The primary outcome was known
      for 335 infants with 33 using surrogate language information. Targeting a lower
      compared with a higher Spo2 target range had no significant effect on the rate of
      death or major disability at 2 years' corrected age (65/167 [38.9%] vs 76/168
      [45.2%]; relative risk 1.15, 95% CI 0.90-1.47) or any secondary outcomes. Death
      occurred in 25 (14.7%) and 27 (15.9%) of those randomized to the lower and higher
      target, respectively, and blindness in 0% and 0.7%. CONCLUSIONS: Although there
      was no benefit or harm from targeting a lower compared with a higher saturation
      in this trial, further information will become available from the prospectively
      planned meta-analysis of this and 4 other trials comprising a total of nearly
      5000 infants.

PMID- 24560182
TI  - Pancreatic enzyme replacement therapy dosing and nutritional outcomes in children
      with cystic fibrosis.
AB  - OBJECTIVES: To utilize the Cystic Fibrosis Foundation Patient Registry to
      evaluate whether pancreatic enzyme dose is associated with better nutritional
      status as measured by average body mass index (BMI) percentile. STUDY DESIGN: A
      retrospective analysis of the Cystic Fibrosis Foundation Patient Registry from
      2005-2008 was performed. The final analysis included 42 561 patient visits from
      14 482 patients 2-20 years of age taking pancreatic enzyme replacement therapy
      from 179 programs. Cystic fibrosis care programs were assigned to quartiles based
      on adjusted mean patient BMI percentiles. Differences in median lipase dose
      between programs in the highest and lowest BMI quartiles were examined using a
      mixed effects model that adjusted for individual patient BMI, age, race,
      ethnicity, forced expiratory volume in 1 second percent, acid-blocker use,
      presence of Pseudomonas aeruginosa, nutritional supplement use, growth hormone
      use, and diagnosis of cystic fibrosis-related diabetes. RESULTS: A significant
      difference in median enzyme dose existed between the highest and lowest BMI
      quartiles. Multivariable analysis demonstrated the effect persisted after
      adjustment for covariates. Highest quartile programs had a median enzyme dose of
      1755 lipase units/kg/meal compared with 1628 lipase units/kg/meal for lowest
      quartile programs. CONCLUSION: Patients attending US cystic fibrosis programs
      achieving highest nutritional outcomes, measured by mean BMI percentile, have
      higher enzyme dosing than those attending programs at lower performance levels.
      Further randomized clinical trials are necessary to determine the role of enzyme
      dose in improving nutritional outcomes.

PMID- 24560183
TI  - Infliximab plus plasma exchange rescue therapy in Kawasaki disease.
AB  - OBJECTIVE: To evaluate infliximab (IFX) in patients with Kawasaki disease (KD)
      that was unresponsive to additional intravenous immunoglobulin (IVIG) therapy and
      subsequent rescue with supplementary plasma exchange (PE) in patients
      unresponsive to treatment. STUDY DESIGN: We studied 76 patients with KD who
      received IVIG therapy twice and were unresponsive to additional IVIG. REULTS:
      Seventy were treated with IFX alone (92.1%). Six patients who were unresponsive
      IFX (7.9%) were further treated by PE. This resulted in disappearance of fever
      and other clinical symptoms, and improvement of laboratory data. There was no
      severe life-threatening adverse events.Twelve of the 76 cases had developed
      coronary artery dilatation, and 3 had coronary artery aneurysm within 1 month of
      disease onset. At the end of follow-up, in all cases, coronary artery lesions
      were suppressed or reversed. CONCLUSIONS: Treatment of intractable KD with
      sequential IVIG, IFX, and PE treatments in a step-wise protocol was effective.

PMID- 24560184
TI  - Impact of hydrocortisone on adult height in congenital adrenal hyperplasia-the
      Minnesota cohort.
AB  - OBJECTIVE: To estimate the impact of the average daily dose of hydrocortisone
      (HC) on the amount of growth attained in children with congenital adrenal
      hyperplasia (CAH). The effect of glucocorticoid therapy on adult height (AH) in
      children with CAH has yet to be elucidated. STUDY DESIGN: Triple-logistic models
      estimating components of growth and maturation were fitted to longitudinal
      records of 104 patients with classic CAH from 3 pediatric medical centers in
      Minnesota between 1955 and 2012. A total of 3664 clinical encounters were
      examined. Random-effects longitudinal models with time-related covariates were
      used to estimate the effect of HC therapy on linear growth. RESULTS: The
      predicted AH z-score (-0.7) was similar between the sexes and among CAH subtypes.
      The mean growth period HC dose was 18.9 +/- 5.6 mg/m(2)/day. In the final
      regression model, HC dose was negatively associated with predicted AH, with each
      mg/m(2)/day increase in average growth period HC dose predicting a 0.37-cm
      decrease in AH (P < .004). CONCLUSION: This study has quantified the fractional
      reduction in predicted final AH with an incremental increase in HC dose. These
      findings have important clinical implications in the decision making balance
      between HC replacement dose and adrenal androgen suppression in children with
      CAH.

PMID- 24560185
TI  - Grip and percussion myotonia in myotonic dystrophy type 1.

PMID- 24560186
TI  - Treatment of anastomotic stenosis and leakage after colorectal resection for
      cancer with self-expandable metal stents.
AB  - BACKGROUND: Self-expandable metallic stents can be used to treat patients with
      symptomatic anastomotic complications after colorectal resection. METHODS: Twenty
      patients with symptomatic anastomotic stricture after colorectal resection were
      treated with endoscopic placement of a self-expandable metal stent. Ten patients
      had "simple" anastomotic stricture. In the remaining 10 patients, a leak was
      associated with the stricture. RESULTS: The anastomotic leakage healed without
      evidence of residual stricture or major fecal incontinence in 8 of 10 patients.
      Overall, the anastomotic stricture was resolved in 14 of the 20 patients.
      CONCLUSIONS: Self-expandable metal stents represent a valid adjunctive to treat
      patients with symptomatic anastomotic complications after colorectal resection
      for cancer. They have a complementary role to balloon dilatation in case of
      simple anastomotic stricture, and they improve the rate of healing when the
      stricture is associated with a leak.

PMID- 24560187
TI  - Osteocytes exposed to far field of therapeutic ultrasound promotes osteogenic
      cellular activities in pre-osteoblasts through soluble factors.
AB  - Low intensity pulsed ultrasound (LIPUS) was reported to accelerate the rate of
      fracture healing. When LIPUS is applied to fractures transcutaneously, bone
      tissues at different depths are exposed to different ultrasound fields.
      Measurement of LIPUS shows pressure variations in near field (nearby transducer);
      uniform profile was found beyond it (far field). Moreover, we have reported that
      the therapeutic effect of LIPUS is dependent on the axial distance of ultrasound
      beam in rat fracture model. However, the mechanisms of how different axial
      distances of LIPUS influence the mechanotransduction of bone cells are not
      understood. To understand the cellular mechanisms underlying far field LIPUS on
      enhanced fracture healing in rat model, the present study investigated the effect
      of ultrasound axial distances on (1) osteocyte, the mechanosensor, and (2)
      mechanotransduction between osteocyte and pre-osteoblast (bone-forming cell)
      through paracrine signaling. We hypothesized that far field LIPUS could enhance
      the osteogenic activities of osteoblasts via paracrine factors secreted from
      osteocytes. The objective of this study was to investigate the effect of axial
      distances of LIPUS on osteocytes and osteocyte-osteoblast mechanotransduction. In
      this study, LIPUS (plane; 2.2 cm in diameter, 1.5MHz sine wave, ISATA=30
      mW/cm(2)) was applied to osteocytes (mechanosensor) at three axial distances: 0mm
      (near field), 60mm (mid-near field) and 130 mm (far field). The conditioned
      medium of osteocytes (OCM) collected from these three groups were used to culture
      pre-osteoblasts (effector cell). In this study, (1) the direct effect of
      ultrasound fields on the mechanosensitivity of osteocytes; and (2) the osteogenic
      effect of different OCM treatments on pre-osteoblasts were assessed. The
      immunostaining results indicated the ultrasound beam at far field resulted in
      more beta-catenin nuclear translocation in osteocytes than all other groups. This
      indicated that osteocytes could detect the acoustic differences of LIPUS at
      various axial distances. Furthermore, we found that the soluble factors secreted
      by far field LIPUS exposed osteocytes could further promote pre-osteoblasts cell
      migration, maturation (transition of cell proliferation into osteogenic
      differentiation), and matrix calcification. In summary, our results of this
      present study indicated that axial distance beyond near field could transmit
      ultrasound energy to osteocyte more efficiently. The LIPUS exposed osteocytes
      conveyed mechanical signals to pre-osteoblasts and regulated their osteogenic
      cellular activities via paracrine factors secretion. The soluble factors secreted
      by far field exposed osteocytes led to promotion in migration and maturation in
      pre-osteoblasts. This finding demonstrated the positive effects of far field
      LIPUS on stimulating osteocytes and promoting mechanotransduction between
      osteocytes and osteoblasts.

PMID- 24560188
TI  - The impact of weight reduction in the prevention of the progression of
      obstructive sleep apnea: an explanatory analysis of a 5-year observational follow
      up trial.
AB  - BACKGROUND: Obstructive sleep apnea (OSA) is a chronic progressive disease, and
      it is well-documented that severe OSA is associated with an increased
      cardiovascular morbidity and mortality. Weight reduction has been shown to
      improve OSA; however, we need further evidence to determine if it may prevent the
      progression of OSA in the long term. The aim of our study was to assess the
      impact of weight change during a 5-year observational follow-up of an original 1
      year randomized controlled trial. METHODS: The participants were divided into the
      two groups according to the weight change at 5-year follow-up using the 5% weight
      loss as a cutoff point, which was later referred to as the successful (n = 20) or
      unsuccessful groups (n = 27). The change in apnea-hypopnea index (AHI) was the
      main objective outcome variable. RESULTS: Fifty-seven patients participated in
      the 5-year follow-up. At 5 years from the baseline, the change in AHI between the
      groups was significant in the successful group (-3.5 [95% confidence interval
      {CI}, -6.1 to -0.9]) compared with the unsuccessful group (5.0 [95% CI, 2.0-8.5])
      (P = .002). Successful weight reduction achieved an 80% reduction in the
      incidence of progression of OSA compared to the unsuccessful group (log-rank
      test, P = .016). CONCLUSIONS: A moderate but sustained weight reduction can
      prevent the progression of the disease or even cure mild OSA in obese patients.

PMID- 24560189
TI  - Impact of frequency of nightmares comorbid with insomnia on depression in
      Japanese rural community residents: a cross-sectional study.
AB  - OBJECTIVE: Nightmares and insomnia are known to be associated with the
      development and aggravation of depression. Our community-based study was
      conducted to clarify the relation between the impacts of nightmares and insomnia
      on depression. METHODS: A cross-sectional questionnaire-based survey was
      administered to residents of a rural community in Japan. In all, 2822
      participants responded to questions assessing personal characteristics, the
      Pittsburgh Sleep Quality Index (PSQI) for assessing insomnia, and a 12-item
      version of the Center for Epidemiological Studies Depression scale (CES-D) for
      evaluating depression. Nightmare frequency was assessed using an item for
      nightmares on the PSQI. RESULTS: Nightmares more frequently occurred in
      participants with insomnia than those without (P < .01). Multiple regression
      analysis revealed that the scores of both nightmares and insomnia were
      significantly associated with the increase in depression score (nightmares (beta
      = 0.09, P < .01); insomnia (beta = 0.39, P < .01)). Participants with coexisting
      nightmares and insomnia showed higher depression scores than participants with
      insomnia alone or those with nightmares who did not have insomnia (P < .01).
      CONCLUSIONS: Insomnia and nightmares independently and additively impact the
      aggravation of depression.

PMID- 24560190
TI  - Selection of response criteria affects the success rate of oral appliance
      treatment for obstructive sleep apnea.
AB  - BACKGROUND: In oral appliance therapy for obstructive sleep apnea (OSA),
      treatment success is arbitrarily defined. We investigated if the selection of
      response criteria affected the success rate of oral appliance treatment. METHODS:
      The effects of an oral appliance on apnea-hypopnea index (AHI) and nadir
      percutaneous oxygen saturation (SpO2) were investigated in 224 OSA patients.
      Treatment success was defined as a reduction in AHI to <5 events per hour with a
      >50% reduction in baseline AHI (criterion 1), a follow-up AHI of <10 events per
      hour with a >50% reduction in baseline AHI (criterion 2), a >50% reduction in
      baseline AHI alone (criterion 3), or a >50% reduction in baseline AHI with the
      nadir SpO2 above 90% (criterion 4). RESULTS: The baseline AHI was reduced with an
      oral appliance in place compared with the follow-up value (23 +/- 11-8.5 +/- 8.7
      events/h; P<.05) in all of the participants. In every OSA subgroup, the success
      rate under criterion 3 (75% [mild], 71% [moderate], and 70% [severe]) was greater
      than that under criterion 1 (53%, 40%, and 24%, respectively). However,
      responders under criterion 3 in the severe OSA subgroup were still hypoxemic with
      a nadir SpO2 of 87 +/- 8% even after treatment. This situation was improved by
      the use of criterion 4, in which a satisfactory improvement in AHI (from 38 +/-
      11 to 1 +/- 1 events/h; P<.01) was associated with a sufficient increase in the
      nadir SpO2 (93 +/- 2%). CONCLUSIONS: We conclude that the selection of response
      criteria influences the success rate of oral appliance treatment. To avoid
      adverse health outcomes, an adjunct definition of treatment success using SpO2
      may be effective for patients who have more severe OSA.

PMID- 24560191
TI  - Constitutive antiviral immunity at the expense of autoimmunity.
AB  - In this issue of Immunity, Funabiki et al. (2014) have identified in mice a
      mutation of the IFIH1 gene, encoding the viral receptor MDA5 that causes
      constitutive IFN production and fatal autoimmune disease. The authors show that
      the autoimmune disease-associated variant of human MDA5 is permanently switched
      on.

PMID- 24560192
TI  - How T cells lose their touch.
AB  - T cells are among the most sensitive of cells, but in this issue of Immunity,
      Honda et al. (2014) demonstrate that effector T cells must lose their touch
      within hours to protect the host from immunopathology.

PMID- 24560193
TI  - Intestinal macrophages and DCs close the gap on tolerance.
AB  - CD103(+) dendritic cells (DCs) must acquire soluble food antigens from the gut
      lumen to induce oral tolerance. In this issue of Immunity, Mazzini et al. (2014),
      report that CX3CR1(+) macrophages capture such antigen and transfer it to the DCs
      by a route involving gap junctions.

PMID- 24560194
TI  - The battle in the gut.
AB  - Our molecular understanding of how pathogen-microbiota-immune system interactions
      influence disease outcomes is limited. In this issue of Immunity, Behnsen et al.
      (2014) report that the cytokine interleukin-22, which usually plays a protective
      role, promotes pathogen colonization by suppressing related commensal bacteria.

PMID- 24560195
TI  - Macrophage activation: glancing into diversity.
AB  - Macrophage activation is a crucial process for innate immunity as well as for
      tissue and metabolic homeostasis. In this issue of Immunity, Xue et al. (2014)
      extend our knowledge on macrophage activation and identify unique functional
      states, thus expanding the M1-M2 paradigm.

PMID- 24560196
TI  - Circadian clock proteins and immunity.
AB  - Immune parameters change with time of day and disruption of circadian rhythms has
      been linked to inflammatory pathologies. A circadian-clock-controlled immune
      system might allow an organism to anticipate daily changes in activity and
      feeding and the associated risk of infection or tissue damage to the host.
      Responses to bacteria have been shown to vary depending on time of infection,
      with mice being more at risk of sepsis when challenged ahead of their activity
      phase. Studies highlight the extent to which the molecular clock, most notably
      the core clock proteins BMAL1, CLOCK, and REV-ERBalpha, control fundamental
      aspects of the immune response. Examples include the BMAL1:CLOCK heterodimer
      regulating toll-like receptor 9 (TLR9) expression and repressing expression of
      the inflammatory monocyte chemokine ligand (CCL2) as well as REV-ERBalpha
      suppressing the induction of interleukin-6. Understanding the daily rhythm of the
      immune system could have implications for vaccinations and how we manage
      infectious and inflammatory diseases. 

PMID- 24560197
TI  - Is there any evidence that the Trans Pacific Partnership Agreement will threaten
      access to affordable medicines and health equity in New Zealand?

PMID- 24560198
TI  - Re: Quantitative hepatic CT perfusion measurement: Comparison of Couinaud's
      hepatic segments with dual-source 128-slice CT.

PMID- 24560201
TI  - [AJUST: prospective study about 60 patients].

PMID- 24560200
TI  - [Multiparametric 3T MRI in the routine staging of prostate cancer].
AB  - OBJECTIVE: To analyse the detection ability of a multiparametric 3T MRI with
      phased-array coil in comparison with the pathological data provided by the
      prostatectomy specimens. METHODS: Prospective study of 30 months, including 74
      patients for whom a diagnosis of prostate cancer had been made on randomized
      prostate biopsies, and all eligible to a radical prostatectomy. They all
      underwent multiparametric 3T MRI with pelvic phased-array coil including T2
      weighted imaging (T2W), dynamic contrast-enhanced (DCE) and diffusion-weighted
      imaging (DWI) with an ADC mapping. Each gland was divided in octants. Three
      specific criteria have been sought (detection ability, capsular contact [CC] and
      extracapsular extension [ECE]), in comparison with the pathological data provided
      by the prostatectomy specimens. RESULTS: Five hundred and ninety-two octants were
      considered with 124 significant tumors (volume >= 0.1cm(3)). The general ability
      of tumor detection had a sensitivity, specificity, PPV and NPV respectively to
      72.3%, 87.4%, 83.2% and 78.5%. The estimate of the CC and ECE had a high negative
      predictive power with specificities and VPN respectively to 96.4% and 95.4% for
      CC, and 97.5 and 97.7% for ECE. CONCLUSIONS: Multiparametric 3T MRI with pelvic
      phased-array coil appeared to be a reliable imaging technique in clinical and
      routine practice for the detection of localized prostate cancer. Estimation of
      the CC and millimeter ECE remains to be clarified, even if the negative
      predictive power for these parameters seems encouraging.

PMID- 24560199
TI  - Magnetic resonance colonography with automated carbon dioxide insufflation:
      Diagnostic accuracy and distension.
AB  - OBJECTIVES: To evaluate the diagnostic performance of MR colonography using
      automated carbon dioxide (CO2) insufflation for colonic distension, with
      colonoscopy serving as the reference standard. METHODS: Ninety-eight symptomatic
      patients underwent MR colonography with faecal tagging and automated CO2
      insufflation. Three readers (one expert (reader 1), and two less experienced
      (readers 2 and 3)) evaluated the images for the presence of colorectal lesions.
      Bowel distension was evaluated on a 4-point scale. Results were verified with
      colonoscopy and histopathological analysis. RESULTS: Per-patient sensitivity for
      lesions >=10mm was 91.7% (11 of 12) (reader 1), 75.0% (9 of 12) (reader 2), and
      75% (9 of 12) (reader 3). Specificity was 96.5% (82 of 85) (reader 1), 97.7% (83
      of 85) (reader 2), 95.3% (81 of 85) (reader 3). Per-patient sensitivity for
      lesions >=6mm was 85.7% (18 of 21) (reader 1), 57.1% (12 of 21) (reader 2), and
      57.1% (12 of 21) (reader 3). Specificity was 86.8% (66 of 76), 98.7% (75 of 76),
      90.8% (69 of 76), respectively. Per-patient sensitivity for advanced neoplasia of
      >=10mm and >=6mm was 88.9% (8 of 9) for all readers. Specificity for >=10mm and
      >=6mm was 98.9% (87 of 88) (reader 1), 97.7% (86 of 88) (reader 2), 96.6% (85 of
      88) (reader 3). 94.4% of the colon segments were adequate to optimal distended
      with dual positioning. CONCLUSION: MR colonography can accurately detect lesions
      >=10mm, and advanced neoplasia >=6mm. Sufficient distension was achieved using
      automated CO2 insufflation for colonic distension in MR colonography.

PMID- 24560202
TI  - [Primary renal synovial sarcoma].
AB  - The primary renal synovial sarcoma is a rare tumor with a poor prognosis. It may
      be confused with other types of mesenchymal kidney tumors because of similarities
      in clinical and histological appearance. About 60 cases have been described in
      the literature. We report a case of a 66-year-old man presenting a primary
      synovial sarcoma of the right kidney with a vascular invasion of the inferior
      vena cava and right renal vein. The diagnosis was confirmed in molecular biology
      by reverse transcription polymerase chain reaction (RT-PCR) which demonstrated a
      unique chromosomal translocation t(X;18) with SYT-SSX2 fusion transcripts. We
      describe here the case with a brief review.

PMID- 24560203
TI  - [Primary signet ring cell carcinoma of the prostate: a rare tumor].
AB  - The prostate is a very rare localization of signet ring cell carcinoma, with few
      cases reported in the literature. This histological type occurs rather in cancers
      of the digestive tract (stomach, colon). Authors report a case of a patient aged
      63 years. Diagnostic and therapeutic features are discussed.

PMID- 24560204
TI  - [Usefulness of urethral endoprosthesis in the management of urinary retention
      after brachytherapy for localized prostate cancer].
AB  - Brachytherapy is a possible treatment for localized low risk prostate cancer.
      Although this option is minimally invasive, some side effects may occur. Acute
      retention of urine (ARU) has been observed in 5% to 22% of cases and can be
      prevented in most cases by alpha-blocker treatment. Several alternatives have
      been reported in the literature for the management of ARU following
      brachytherapy: prolonged suprapubic catheterization, transurethral resection of
      the prostate and also intermittent self-catheterization. The authors report an
      original endoscopic approach, using urethral endoprosthesis, with a satisfactory
      voiding status. 

PMID- 24560205
TI  - [Stage IV prostate cancer in Guadeloupe, a French Caribbean archipelago].
AB  - OBJECTIVES: To study clinical characteristics, in terms of survival and response
      to treatment, of patients with non-localized prostate cancer at diagnosis in an
      Afro-Caribbean population from Guadeloupe. METHODS: Cases of stage IV prostate
      cancer (T4N0M0, TxN1M0 and TxNxM1) at diagnosis in the Pointe a Pitre Hospital
      were selected from 1995 to 2012 and studied. RESULTS: One hundred and eighty
      three patients were included. Median age at diagnosis was 70.3 years old (79.2%
      were more than 65 years). A total of 81.5% of them was TxNxM1 and 11.5% was
      TxN1M0. Median disease free survival was 18.5 months. Median overall survival was
      49.0 months. CONCLUSION: This study about non-localized prostate cancer at
      diagnosis in an Afro-Caribbean population from a French Caribbean archipelago
      seemed to show no difference with general population suffering from the same
      disease, although prostate cancer incidence in this area is one of the highest in
      the world.

PMID- 24560206
TI  - [Open versus laparoscopic radical prostatectomy: a French center experience].
AB  - OBJECTIVE: To compare peri-operative outcomes of open radical prostatectomy (ORP)
      to laparoscopic radical prostatectomy (LRP) in a single French institution.
      METHODS: Between 1998 and 2003, 72 patients underwent ORP followed by 279 LRP
      between 2003 and 2010 for a clinically localized prostate cancer. Demographic,
      peri-operative and pathological data in the ORP and LRP groups were analyzed and
      compared. RESULTS: In the ORP group, compared to the LRP group, the following
      significant differences were found: patients were older (63.1 years versus 65.6),
      initial PSA was higher (10.2 ng/mL versus 6.7) and the proportion of T1c was
      higher (62.8 % versus 80.6 %). Operative blood loss (1500 mL versus 500) and
      length of hospitalization (9.0 days versus 6.3) were higher in the ORP group
      (P<0.001). Operative time was longer in the LRP group (250 min versus 160; P<0
      .001). There was no significant difference regarding length of catheterization
      (average of 8.5 days). Anastomotic strictures were more frequent following ORP
      (P<0.001). Positive margins proportion in the ORP group (7.1 %) was lower than
      that observed in the LRP group (28.7 %) (P=0.001). Patients in the ORP group
      achieved early continence more frequently (P<0.01) but at 12 months
      postoperatively there was no significant difference. CONCLUSION: Patients in the
      LRP group had lower operative blood losses and a shorter length of
      hospitalization. However, in the ORP group, operative time was shorter and
      positive margins rate was lower.

PMID- 24560207
TI  - [Local consultations by specialists in urology: an answer to patients'
      expectations and dwindling physician numbers?].
AB  - OBJECTIVE: To analyze patients' views with regards to local consultations given
      by specialists in urology and to an offer of pre- and postoperative visits in the
      local general hospital with surgical interventions taking place at the university
      hospital. MATERIALS AND METHODS: An opinion survey by mail questionnaire was
      carried out in all 473 patients who had had a consultation with a specialist in
      two local general hospitals between November 2009 and April 2010. RESULTS:
      Response rate was 74%. Mean patient age was 65.5 +/- 12 years [range, 20-90]. The
      reason for the consultation was cancer-related in 31.2% of patients. The majority
      (89%) made the journey to hospital under their own steam and would have had to
      travel a 4 times greater distance if the consultation with the specialist had
      taken place at the university hospital. Overall, 54.6% of patients were willing
      to travel 20 km further to see a specialist and 76.5% were willing to travel 20
      km further for a surgical intervention. Virtually all of the patients (>99%) saw
      benefits to local consultations given by specialists. The offer of a consultation
      at the general hospital and intervention at the university hospital met with the
      approval of 60.8% patients and 56.3% had already experimented this offer.
      CONCLUSION: Local consultations by specialists might be an answer to demographic
      issues in France, that is, to the small number of urologists practicing in
      general hospitals.

PMID- 24560208
TI  - [Eight years of experience in robot-assisted partial nephrectomy: oncological and
      functional outcomes].
AB  - INTRODUCTION: Partial nephrectomy (PN) is currently the reference treatment for
      renal tumors of less than 4 cm in size (T1a). Laparoscopic PN is difficult to
      perform, with the main consequence being an increase in warm ischemia time and
      morbidity. In facilitating the surgical procedure, robotics combines the benefits
      of minimally invasive and conservative surgery. We report here 8 years of
      experience with 110 robot-assisted partial nephrectomies (RAPN). The objective of
      this study was to analyze the oncological and functional outcomes. PATIENTS AND
      METHODS: Between March 2005 and September 2012, 110 patients underwent RAPN. The
      epidemiological and surgical data and the oncological and functional outcomes
      were retrospectively collected and analyzed. RESULTS: Seventy-six men and 34
      women underwent surgery. The mean age was 59.6 +/- 14.2 years. Mean operative
      time was 141.3 +/- 36.1 minutes with a warm ischemia time of 21.2 +/- 8.8
      minutes. Mean hospital stay was 5.3 +/- 2.2 days. Mean tumor size was 27.4 +/-
      9.8mm with 82.7% malignant tumors, of which 62.7% were clear cell carcinomas.
      Surgical margins were healthy in 100% of cases. After a mean follow-up of 28.7 +/
      18.5 months, no recurrence was noted. On a functional level, there was no short
      term or medium-term impairment of renal function. The frequency of postoperative
      complications was estimated as 12% including 7% of surgical complications (3
      arterial pseudoaneurysms, 4 episodes of bleeding from the cut surface and 1
      conversion to laparotomy). CONCLUSION: Robotics brought surgeon dexterity,
      meticulousness and precision. These qualities are essential in conservative renal
      surgery and made RAPN a safe and effective technique that gives good short and
      medium-term oncological and functional results.

PMID- 24560209
TI  - [Analysis of postoperative urgenturies after prostate photovaporization by the
      laser Greenlight (r)].
AB  - Urgencies are classically described after prostate photovaporization (PVP). The
      objective of this study was to analyze the incidence of urgency in patients who
      underwent PVP using the International Prostate Symptom Score (IPSS) to defined
      urgencies. METHOD: This is a single-center prospective cohort study assessing
      patients who underwent surgery between May 2005 and January 2011. The questions 2
      and 4 of the IPSS and open questions were selected to evaluate urgency during the
      follow-up. RESULTS: Two-hundred and four patients were operated during this
      period and 93 complete records were analyzed. Twenty-one percent of these
      patients had a clinical urgency after 1 month and 1,9% at 12 months (significant
      improvement, P<0.001) corresponding to scores greater than 4 for questions 2 and
      4 of the IPSS. Answer scores to questions 2 and 4 improved significantly over 12
      months (P<0.001). The clinical urgencies decreased significantly as well as
      answers to questions 2 and 4 of the IPSS. CONCLUSION: Urgencies decreased
      significantly between 3 and 12 months of postoperative follow. Questions 2 and 4
      of the IPSS score appeared to be a standardized definition of these urgencies.

PMID- 24560210
TI  - [Evolution of lower urinary tract symptoms under silodosin: factors influencing
      patients' satisfaction].
AB  - The objective of this study was to analyze the efficacy and safety of silodosin
      in patients with lower urinary tract symptoms (LUTS) associated with benign
      prostatic hyperplasia (BPH) in current urologic practice. METHOD: This was a
      prospective observational study conducted by 272 urologists on patients treated
      by silodosin for BPH. The parameters evaluated were the weighted IPSS score, the
      IPSS question 8 related to quality of life, the USP score and the Athens Insomnia
      Scale (AIS) measured at treatment initiation and after 3 months. RESULTS: Nine
      hundred and fourteen patients whose average age was 66 years with LUTS for 3.3
      years were analyzed. After 3 months of treatment, a significant decrease in IPSS
      (from 16.2 +/- 6.1 to 9.7 +/- 5.5, P<0.0001) and USP score (from 10.6 +/- 5.1 to
      6 0 +/- 4.6, P<0.0001) were observed, quality of life (from 67.1% to 14.4% of
      unsatisfied patients, P<0.0001) and sleep were significantly improved (from 49.2%
      to 28.9% patients with insomnia, P<0.0001). Among the patients, 21.2% experienced
      at least one adverse event. The most frequent were abnormal ejaculation (17.2%).
      And 7.1% discontinued the treatment for this reason. After 3 months of treatment
      silodosin was continued in 86.9% of patients. CONCLUSION: This large study
      confirmed the efficacy of silodosin in LUTS associated with BPH with a safety
      profile that does not affect patient satisfaction.

PMID- 24560211
TI  - [Medical and surgical treatments of congenital and acquired penile curvatures: a
      review].
AB  - INTRODUCTION: The aim of the current study was to provide an overview about the
      surgical and medical management of acquired and congenital penile's curvature.
      MATERIALS AND METHODS: [corrected] A systematic review of the literature was done
      from the PubMed database by searching the following keywords alone or in
      combination: Congenital penile curvature; Congenital penile deviation; Acquired
      penile curvature; Acquired penile deviation; Peyronie's disease. RESULTS: The
      treatment of congenital curvature is only surgical. The most common technique is
      the Nesbit's technique which consists in making elliptical excisions of the
      tunica albuginea. There are also incison or plication procedures which are
      efficient as well. Acquired curvature is most of the time represented by the
      Peyronie's disease or is post-traumatic. Among oral treatments available, the
      Potaba is the only drug which has proved a significant reduction in penile plaque
      size. Injections of interferon and nicardipine have also shown their efficacy.
      Ionotophoresis and extracorporeal shock-wave therapy may be beneficial for penile
      pain. Other therapies (vacuum, traction devices, topical Verapamil) can be
      interesting but other studies are necessary to recommend them. Surgical treatment
      is recommended during the fibrotic phase. The most common technique is also the
      Nesbit's technique. In case of severe curvature (curve superior to 60 degrees ),
      small penis, major deformations, graft techniques can be used. Moreover, if there
      is a sexual dysfunction, penile prosthesis is recommended. CONCLUSION: Other
      studies are necessary to prove the efficacy of most of the drugs already
      available in the treatment of the penile curvature. It seems to be interesting to
      combine the different treatments to improve the results of those therapies.

PMID- 24560212
TI  - Prognostic value of PET myocardial perfusion imaging in obese patients.
AB  - OBJECTIVES: This study sought to determine and compare the prognostic and
      incremental value of positron emission tomography (PET) in normal, overweight,
      and obese patients. BACKGROUND: Cardiac rubidium 82 (Rb-82) PET is increasingly
      being used for myocardial perfusion imaging (MPI). A strength of PET is its
      accurate attenuation correction, thereby potentially improving its diagnostic
      accuracy in obese patients. The prognostic value of PET in obese patients has not
      been well studied. METHODS: A total of 7,061 patients who had undergone Rb-82 PET
      MPI were entered into a multicenter observational registry. All patients
      underwent pharmacologic Rb-82 PET and were followed for cardiac death and all
      cause mortality. Based on body mass index (BMI), patients were categorized as
      normal (<25 kg/m(2)), overweight (25 to 29.9 kg/m(2)), or obese (>=30 kg/m(2)).
      Using a 17-segment model and 5-point scoring system, the percentage of abnormal
      myocardium was calculated for stress and rest patients categorized as normal
      (0%), mild (0.1% to 9.9%), moderate (10% to 19.9%), and severe (>=20%). RESULTS:
      A total of 6,037 patients were followed for cardiac death (median: 2.2 years) and
      the mean BMI was 30.5 +/- 7.4 kg/m(2). A total of 169 cardiac deaths were
      observed. PET MPI demonstrated independent and incremental prognostic value over
      BMI. Normal PET MPI conferred an excellent prognosis with very low annual cardiac
      death rates in normal (0.38%), overweight (0.43%), and obese (0.15%) patients. As
      well, both moderately and severe obese patients with a normal PET MPI had
      excellent prognosis (0.20% and 0.10%, respectively). The net reclassification
      improvement of PET was 0.46 (95% confidence interval [CI]: 0.31 to 0.61), and
      appeared similar in the moderately and severe obese patients which were 0.44 (95%
      CI: 0.12 to 0.76) and 0.63 (95% CI: 0.27 to 0.98), respectively. CONCLUSIONS: Rb
      82 PET has incremental prognostic value in all patients irrespective of BMI. In
      the obese population, where other modalities may have reduced diagnostic
      accuracy, cardiac PET appears to be a promising noninvasive modality with
      prognostic value.

PMID- 24560213
TI  - Accuracy of transcranial Doppler for the diagnosis of intracardiac right-to-left
      shunt: a bivariate meta-analysis of prospective studies.
AB  - OBJECTIVES: The aim of this meta-analysis was to determine the accuracy of
      transcranial Doppler (TCD) compared with transesophageal echocardiography (TEE)
      as the reference. BACKGROUND: Right-to-left shunting (RLS), usually through a
      patent foramen ovale (PFO), has been associated with migraine, cryptogenic
      stroke, and hypoxemia. With emerging observational studies and clinical trials on
      the subject of PFO, there is a need for accurate diagnosis of PFO in patients
      with these conditions, and those being considered for transcatheter closure.
      Although a TEE bubble study is the current standard reference for diagnosing PFO,
      the TCD bubble study may be a preferable alternative test for RLS because of its
      high sensitivity and specificity, noninvasive nature, and low cost. METHODS: A
      systematic review of Medline, the Cochrane Library, and Embase was done to look
      for all the prospective studies assessing intracardiac RLS using TCD compared
      with TEE as the reference; both tests were performed with a contrast agent and a
      maneuver to provoke RLS in all studies. RESULTS: A total of 27 studies (29
      comparisons) with 1,968 patients (mean age 47.8 +/- 5.7 years; 51% male)
      fulfilled the inclusion criteria. The weighted mean sensitivity and specificity
      for TCD were 97% and 93%, respectively. Likewise, the positive and negative
      likelihood ratios were 13.51 and 0.04, respectively. When 10 microbubbles was
      used as the embolic cutoff for a positive TCD study, TCD produced a higher
      specificity compared with when 1 microbubble was used as the cutoff (p = 0.04);
      there was, however, no significant change in sensitivity (p = 0.29). CONCLUSIONS:
      TCD is a reliable, noninvasive test with excellent diagnostic accuracies, making
      it a proficient test for detecting RLS. TCD can be used as a part of the stroke
      workup and for patients being considered for PFO closure. If knowledge of the
      precise anatomy is required, then TEE can be obtained before scheduling a patient
      for transcatheter PFO closure.

PMID- 24560214
TI  - CMR sensitivity varies with clinical presentation and extent of cell necrosis in
      biopsy-proven acute myocarditis.
AB  - OBJECTIVES: The aim of this study was to determine whether clinical presentation
      and type of cell death in acute myocarditis might contribute to cardiac magnetic
      resonance (CMR) sensitivity. BACKGROUND: Growing evidence indicates CMR is the
      reference noninvasive tool for the diagnosis of acute myocarditis. However,
      factors affecting CMR sensitivity are still unclear. METHODS: We retrospectively
      evaluated 57 consecutive patients with a diagnosis of acute myocarditis made on
      the basis of clinical history (<=3 months) and endomyocardial biopsy evidence of
      lymphocytic infiltrates (>=14 infiltrating leukocytes/mm(2) at
      immunohistochemistry) in association with damage of the adjacent myocytes and
      absence or minimal evidence of myocardial fibrosis. CMR acquisition protocol
      included T2-weighted (edema), early (hyperemia), and late (fibrosis/necrosis)
      gadolinium enhancement sequences. Presence of >=2 CMR criteria denoted
      myocarditis. Type of cell death was evaluated by using in situ ligation with
      hairpin probes. RESULTS: Three clinical myocarditis patterns were recognized:
      infarct-like (pattern 1, n = 21), cardiomyopathic (pattern 2, n = 21), and
      arrhythmic (pattern 3, n = 15). Tissue edema was observed in 81% of pattern 1,
      28% of pattern 2, and 27% of pattern 3. Early enhancement was evident in 71% of
      pattern 1, 67% of pattern 2, and 40% of pattern 3. Late gadolinium enhancement
      was documented in 71% of pattern 1, 57% of pattern 2, and 47% of pattern 3. CMR
      sensitivity was significantly higher in pattern 1 (80%) compared with pattern 2
      (57%) and pattern 3 (40%) (p < 0.05). Cell necrosis was the prevalent mechanism
      of death in pattern 1 compared with pattern 2 (p < 0.001) and pattern 3 (p <
      0.05), whereas apoptosis prevailed in pattern 2 (p < 0.001 vs. pattern 1 and p <
      0.05 vs. pattern 3). CONCLUSIONS: In acute myocarditis, CMR sensitivity is high
      for infarct-like, low for cardiomyopathic, and very low for arrhythmic clinical
      presentation; it correlates with the extent of cell necrosis-promoting expansion
      of interstitial space.

PMID- 24560215
TI  - Gastrointestinal parasites in relation to host traits and group factors in wild
      meerkats Suricata suricatta.
AB  - Meerkats are one of the most endearing of South African's wildlife celebrities
      and one of the most highly studied social mammals. However, although parasites
      are widely recognized as important regulatory factors in animal population, basic
      knowledge on meerkats' parasites is lacking. Here 100 fresh fecal samples of wild
      meerkats were examined for the presence of endoparasitic infection. Endoparasitic
      taxa identified by the presence of eggs or oocysts included Toxocara suricattae,
      Oxynema suricattae, Pseudandrya suricattae, Cystoisospora sp. and Eimeria sp. Non
      specific diagnoses were made for parasites in the Order Strongylida, Order
      Spirurida and coccidian based on the morphology and size of the eggs and oocysts.
      The prevalence of infection with T. suricattae and the strongylate species
      increased with age, while prevalence of coccidia and intensity of infection by
      the strongylate species increased with decreasing group size, suggesting that
      stress associated with living in smaller group may increase susceptibility to
      parasitism. Moreover, parasite communities were more similar between individuals
      from the same group than between individuals from different groups, suggesting an
      important role of the environment in parasite infestation. We did not detect any
      differences between males and females. This study represents the first detailed
      report of gastrointestinal parasites in wild meerkats, and is a key starting
      point for future studies on the effect of endoparasite load in the life history
      of this species.

PMID- 24560217
TI  - A new approach for the Bakri balloon for placenta previa.

PMID- 24560218
TI  - The effect of belonging to an alcohol-proscribing religious group on the
      relationship between moderate alcohol consumption and mortality.
AB  - The purpose of this study was to examine whether belonging to a religious group
      that proscribes alcohol use moderated the relationship between moderate alcohol
      use and mortality. Data came from the Americans' Changing Lives study, based on a
      representative probability sample of adults 25 and older in the US, including
      3390 participants (2135 female). Survey data were collected in 1986, and
      mortality tracked by death certificate through 2005. Proportional hazards
      modeling indicated that, consistent with previous research, moderate alcohol
      consumption (two drinks or fewer per day on average) was related with lower
      mortality compared with both total abstention from alcohol and heavy consumption
      (more than two drinks per day) among participants who did not belong to an
      alcohol-proscribing group. By contrast, moderate drinkers who belonged to alcohol
      proscribing groups had higher mortality risk compared with non-drinkers. Means
      comparisons suggested possible group differences including health behaviors
      (moderate drinkers in proscribing groups drank somewhat less often but more on
      each occasion and were more likely to smoke) and social relationships (they had
      fewer close friends, felt more isolated, and had more negative social
      interactions). Members of religious groups that proscribe alcohol use may have
      health risks associated with moderate alcohol use that are not present in the
      general population. Practitioners should be aware of religious cultural
      differences when assessing individuals' risk from alcohol use. 

PMID- 24560220
TI  - Can social capital help explain enrolment (or lack thereof) in community-based
      health insurance? Results of an exploratory mixed methods study from Senegal.
AB  - CBHI has achieved low population coverage in West Africa and elsewhere. Studies
      which seek to explain this point to inequitable enrolment, adverse selection,
      lack of trust in scheme management and information and low quality of health
      care. Interventions to address these problems have been proposed yet enrolment
      rates remain low. This exploratory study proposes that an under-researched
      determinant of CBHI enrolment is social capital. Fieldwork comprising a household
      survey and qualitative interviews was conducted in Senegal in 2009. Levels of
      bonding and bridging social capital among 720 members and non-members of CBHI
      across three case study schemes are compared. The results of the logistic
      regression suggest that, controlling for age and gender, in all three case
      studies members were significantly more likely than non-members to be enrolled in
      another community association, to have borrowed money from sources other than
      friends and relatives and to report having control over all community decisions
      affecting daily life. In two case studies, having privileged social relationships
      was also positively correlated with enrolment. After controlling for additional
      socioeconomic and health variables, the results for borrowing money remained
      significant. Additionally, in two case studies, reporting having control over
      community decisions and believing that the community would cooperate in an
      emergency were significantly positively correlated with enrolment. The results
      suggest that CBHI members had greater bridging social capital which provided them
      with solidarity, risk pooling, financial protection and financial credit.
      Qualitative interviews with 109 individuals selected from the household survey
      confirm this interpretation. The results ostensibly suggest that CBHI schemes
      should build on bridging social capital to increase coverage, for example by
      enrolling households through community associations. However, this may be
      unadvisable from an equity perspective. It is concluded that since enrolment in
      CBHI was less common not only among the poor, but also among those with less
      social capital and less power, strategies should focus on removing social as well
      as financial barriers to  financial protection from the cost of ill health. 

PMID- 24560221
TI  - Effect of the Crisis Assistance Program on poverty transition for seriously ill
      people in South Korea: a quasi-experimental study.
AB  - The Crisis Assistance Program (CAP) is a newly developed social protection scheme
      in South Korea. It was implemented in 2006 in order to assist individuals
      experiencing a sudden or temporary financial emergency. CAP provides temporary
      assistance to cover the direct user fees associated with inpatient care up to
      three or six million KRW (US $2673-5346). In this study, we aimed to compare the
      poverty dynamics in recipients versus non-recipients and to determine whether
      there is an association between participation in CAP and poverty transition. For
      the purpose, we analyzed longitudinal data from 2009 to 2011 from 55,710 people
      who requested CAP during a serious illness at local governmental offices
      throughout South Korea. During the 1.6 years of follow-up, 8712 (15.6%) of those
      who requested CAP fell into absolute poverty. Results showed that there was a 16%
      reducing effect of CAP on poverty transition (hazard ratio [HR] 0.84, 95%
      confidence interval [CI] 0.79-0.90, p < 0.001) and there was a 33% delay in the
      time to falling into poverty (time ratio [TR] 1.33, 95% CI 1.20-1.47, p < 0.001)
      after adjusting for covariates. In this analysis model, the risk of poverty
      transition induced by experiencing a serious illness decreased rapidly with time
      (ancillary parameter [AP] 0.61, 95% CI 0.59-0.62). The results were essentially
      unchanged even after performing a rigorous propensity analysis, which limited the
      analyses to 12,944 propensity-matched subjects (HR 0.84, 95% CI 0.77-0.91, p <
      0.001; TR 1.38, 95% CI 1.18-1.61, p < 0.001; AP 0.54, 95% CI 0.52-0.57). Our
      findings provide additional evidence for recommending the use of a payment
      strategy that relieves out-of-pocket payments so as to reduce medical
      impoverishment. A temporary assistance scheme for people experiencing a serious
      illness may be an alternative healthcare financing strategy to confront the issue
      of health inequality among the medically and socioeconomically vulnerable. 

PMID- 24560219
TI  - Social capital and chronic post-traumatic stress disorder among survivors of the
      2007 earthquake in Pisco, Peru.
AB  - This study aimed to evaluate the association between chronic Post-Traumatic
      Stress Disorder (PTSD) and both structural and cognitive social capital in adult
      survivors of the 2007 earthquake in Pisco, Peru. Cognitive social capital
      measures trust, sense of belonging and interpersonal relationships in the
      community and structural social capital measures group membership, support from
      community groups and individuals, and involvement in citizenship activities. We
      conducted a population-based cross-sectional study in five counties in Pisco,
      selecting 1012 adults through complex, multi-stage random sampling. All
      participants completed socio-demographic questions and validated Spanish-language
      versions of the Adapted Social Capital Assessment Tool (SASCAT) and the civilian
      PTSD checklist (PCL-C). After performing descriptive and bivariate analyses, we
      carried out prevalence ratio (PR) regression. The overall prevalence of chronic
      PTSD was 15.9% (95% CI: 12.3, 19.8), much higher than anticipated based on
      existing evidence. Cognitive social capital was found to be negatively associated
      with chronic PTSD, while no significant association was found for structural
      social capital. Specifically, those with high cognitive social capital had an
      almost two times lower prevalence of chronic PTSD (PR = 1.83, 95% CI: 1.50, 2.22)
      compared with those with low cognitive social capital. No independent association
      between structural social capital and chronic PTSD was found (PR = 1.44, 95% CI:
      0.70, 2.97). In conclusion, cognitive social capital, but not structural social
      capital, has a protective influence on the occurrence of chronic PTSD in
      survivors of natural disasters. These results may have public health
      implications. For example, pre- and post-disaster community-based interventions
      that catalyze and foster dimensions of cognitive social capital may aid in
      ameliorating the effect of earthquakes and other natural disasters on populations
      with high vulnerability to such events and poor access to mental health and other
      support services. 

PMID- 24560222
TI  - Social inequality in infant mortality: what explains variation across low and
      middle income countries?
AB  - Growing work demonstrates social gradients in infant mortality within countries.
      However, few studies have compared the magnitude of these inequalities cross
      nationally. Even fewer have assessed the determinants of social inequalities in
      infant mortality across countries. This study provides a comprehensive and
      comparative analysis of social inequalities in infant mortality in 53 low-and
      middle-income countries (LMICs). We used the most recent nationally
      representative household samples (n = 874,207) collected through the Demographic
      Health Surveys (DHS) to calculate rates of infant mortality. The relative and
      absolute concentration indices were used to quantify social inequalities in
      infant mortality. Additionally, we used meta-regression analyses to examine
      whether levels of inequality in proximate determinants of infant mortality were
      associated with social inequalities in infant mortality across countries.
      Estimates of both the relative and the absolute concentration indices showed a
      substantial variation in social inequalities in infant mortality among LMICs.
      Meta-regression analyses showed that, across countries, the relative
      concentration of teenage pregnancy among poorer households was positively
      associated with the relative concentration of infant mortality among these groups
      (beta = 0.333, 95% CI = 0.115 0.551). Our results demonstrate that the
      concentration of infant deaths among socioeconomically disadvantaged households
      in the majority of LMICs remains an important health and social policy concern.
      The findings suggest that policies designed to reduce the concentration of
      teenage pregnancy among mothers in lower socioeconomic groups may mitigate social
      inequalities in infant mortality. 

PMID- 24560223
TI  - The failure of financial incentive? The seemingly inexorable rise of cesarean
      section.
AB  - Two policy interventions in Taiwan aiming to slow the growth of cesarean delivery
      utilization were respectively implemented in 2005 and 2006. The first policy
      provided financial incentives to encourage vaginal delivery by setting a global
      fee for obstetric services and in essence increasing the reimbursement for
      vaginal delivery up to the same level of cesarean section. The second policy
      aimed to reduce the demand for elective cesarean procedure by employing a
      copayment when cesarean section is not medically indicated. This paper examines
      the impact of financial incentives of both the supply and the demand side on the
      use of utilization of cesarean section using data from the 2003-2008 National
      Health Insurance Research Database. We found that while the overall trend of
      cesarean utilization did not seem to respond to the interventions, the policies
      did have significant impact on its elective use. Financial incentives for the
      providers do matter, and policy interventions, such as a fee change, are still
      important strategies to consider in reducing the over-utilization of cesarean
      section. 

PMID- 24560225
TI  - Public social monitoring reports and their effect on a policy programme aimed at
      addressing the social determinants of health to improve health equity in New
      Zealand.
AB  - The important role that monitoring plays in advancing global health is well
      established. However, the role of social monitoring as a tool for addressing
      social determinants of health (SDH) and health equity-focused policies remains
      under-researched. This paper assesses the extent and ways in which New Zealand's
      (NZ) Social Reports (SRs) supported a SDH- and health equity-oriented policy
      programme nationally over the 2000-2008 period by documenting the SRs' history
      and assessing its impact on policies across sectors in government and civil
      society. We conducted key-informant interviews with five senior policy-makers and
      an e-mail survey with 24 government and civil society representatives on SRs'
      history and policy impact. We identified common themes across these data and
      classified them accordingly to assess the intensity of the reports' use and their
      impact on SDH- and health equity-focused policies. Bibliometric analyses of
      government publications and media items were undertaken to empirically assess
      SRs' impact on government and civil society. SRs in NZ arose out of the role
      played by government as the "benevolent social welfare planner" and an
      understanding of the necessity of economic and social security for "progress".
      The SRs were linked to establishing a government-wide programme aimed at reducing
      inequalities. They have been used moderately to highly in central and local
      government and in civil society, both within and outside the health sector, but
      have neither entered public treasury and economic development departments nor the
      commercial sector. The SRs have not reached the more universal status of economic
      indicators. However, they have had some success at raising awareness of, and have
      stimulated isolated action on, SDH. The NZ case suggests that national-level
      social monitoring provides a valuable tool for raising awareness of SDH across
      government and civil society. A number of strategies could improve social
      reports' effectiveness in stimulating action on SDH. 

PMID- 24560224
TI  - Socioeconomic inequalities in health after age 50: are health risk behaviors to
      blame?
AB  - Recent studies indicate that socioeconomic inequalities in health extend into the
      elderly population, even within the most highly developed welfare states. One
      potential explanation for socioeconomic inequalities in health focuses on the
      role of health behaviors, but little is known about the degree to which health
      behaviors account for health inequalities among older adults, in particular.
      Using data from the Health and Retirement Study (N = 19,245), this study examined
      the degree to which four behavioral risk factors - smoking, obesity, physical
      inactivity, and heavy drinking - are associated with socioeconomic position among
      adults aged 51 and older, and whether these behaviors mediate socioeconomic
      differences in mortality, and the onset of disability among those who were
      disability-free at baseline, over a 10-year period from 1998 to 2008. Results
      indicate that the odds of both smoking and physical inactivity are higher among
      persons with lower wealth, with similar stratification in obesity, but primarily
      among women. The odds of heavy drinking decrease at lower levels of wealth.
      Significant socioeconomic inequalities in mortality and disability onset are
      apparent among older men and women; however, the role that health behaviors play
      in accounting for these inequalities differs by age and gender. For example,
      these health behaviors account for between 23 and 45% of the mortality
      disparities among men and middle aged women, but only about 5% of the disparities
      found among women over 65 years. Meanwhile, these health behaviors appear to
      account for about 33% of the disparities in disability onset found among women
      survivors, and about 9-14% among men survivors. These findings suggest that
      within the U.S. elderly population, behavioral risks such as smoking and physical
      inactivity contribute moderately to maintaining socioeconomic inequalities in
      health. As such, promoting healthier lifestyles among the socioeconomically
      disadvantaged older adults should help to reduce later life health inequalities. 

PMID- 24560216
TI  - Comparison between the behavior of different hydrophobic peptides allowing
      membrane anchoring of proteins.
AB  - Membrane binding of proteins such as short chain dehydrogenase reductases or tail
      anchored proteins relies on their N- and/or C-terminal hydrophobic transmembrane
      segment. In this review, we propose guidelines to characterize such hydrophobic
      peptide segments using spectroscopic and biophysical measurements. The secondary
      structure content of the C-terminal peptides of retinol dehydrogenase 8, RGS9-1
      anchor protein, lecithin retinol acyl transferase, and of the N-terminal peptide
      of retinol dehydrogenase 11 has been deduced by prediction tools from their
      primary sequence as well as by using infrared or circular dichroism analyses.
      Depending on the solvent and the solubilization method, significant structural
      differences were observed, often involving alpha-helices. The helical structure
      of these peptides was found to be consistent with their presumed membrane
      binding. Langmuir monolayers have been used as membrane models to study lipid
      peptide interactions. The values of maximum insertion pressure obtained for all
      peptides using a monolayer of 1,2-dioleoyl-sn-glycero-3-phospho-ethanolamine
      (DOPE) are larger than the estimated lateral pressure of membranes, thus
      suggesting that they bind membranes. Polarization modulation infrared reflection
      absorption spectroscopy has been used to determine the structure and orientation
      of these peptides in the absence and in the presence of a DOPE monolayer. This
      lipid induced an increase or a decrease in the organization of the peptide
      secondary structure. Further measurements are necessary using other lipids to
      better understand the membrane interactions of these peptides. 

PMID- 24560226
TI  - National electronic health records and the digital disruption of moral orders.
AB  - The digitalisation of patient health data to provide national electronic health
      record systems (NEHRS) is a major objective of many governments. Proponents claim
      that NEHRS will streamline care, reduce mistakes and cut costs. However, building
      these systems has proved highly problematic. Using recent developments in
      Australia as an example, we argue that a hitherto unexamined source of difficulty
      concerns the way NEHRS disrupt the moral orders governing the production,
      ownership, use of and responsibility for health records. Policies that pursue
      digitalisation as a self-evident 'solution' to problems in healthcare without due
      regard to these disruptions risk alienating key stakeholders. We propose a more
      emergent approach to the development and implementation of NEHRS that supports
      moral re-ordering around rights and responsibilities appropriate to the
      intentions of those involved in healthcare relationships. 

PMID- 24560227
TI  - Against all odds? Understanding the emergence of accreditation of the Danish
      hospitals.
AB  - Despite intense critique from various parts of the medical professions, Danish
      hospitals have been subjected to a mandatory accreditation system known as the
      Danish Quality Model (Den Danske Kvalitetsmodel, DDKM) since 2009. The notion of
      government assemblage is employed to understand how and why, in the face of these
      obstacles, DDKM was ultimately implemented. It is argued that DDKM is the result
      of the emergence of hospital quality management assemblage in 1980s and 1990s
      made up by new methods of categorizing disease treatments, computerization of
      such treatments, concerns over cost-effectiveness, complaint registration, the
      availability of international hospital quality assessment systems, the
      mobilization of organized medical interest groups, and a tradition of
      consultative policymaking procedures. This assemblage was crucial for identifying
      quality as a problem in need of administrative intervention and for shaping the
      political struggle over how best to assure the quality of hospital services. 

PMID- 24560228
TI  - Discussing dying in the diaspora: attitudes towards advance care planning among
      first generation Dutch and Italian migrants in rural Australia.
AB  - Western cultural practices and values have largely shaped advance care planning
      (ACP) policies across the world. Low uptake of ACP among ethnic minority groups
      in Western countries has been interpreted with reference to cultural differences.
      This paper adopts a life-history approach to explore attitudes towards ACP among
      older, first-generation Dutch-Australian and Italian-Australian migrants. Thirty
      people participated in extended ethnographic interviews (N = 17) and group
      discussions (N = 13) during 2012. Transcripts were thematically analyzed and
      interpreted using a Foucauldian perspective on knowledge and power. Migration
      experiences, ongoing contact with the native country and participation in migrant
      community support networks influenced attitudes towards ACP. Dutch participants
      framed ACP discussions with reference to euthanasia, and adopted a more
      individualist approach to medical decision-making. Italian participants often
      spoke of familial roles and emphasized a family-based decision making style. The
      importance of migrant identity has been neglected in previous discussions of
      cultural factors influencing ACP uptake among ethnic minority groups. The unique
      migration experience should be considered alongside culturally appropriate
      approaches to decision-making, in order to ensure equitable access to ACP among
      migrant groups. 

PMID- 24560230
TI  - Teaching hospital performance: towards a community of shared values?
AB  - This paper explores the performance dimensions of Italian teaching hospitals
      (THs) by considering the multiple constituent model approach, using measures that
      are subjective and based on individual ideals and preferences. Our research
      replicates a study of a French TH and deepens it by adjusting it to the context
      of an Italian TH. The purposes of this research were as follows: to identify
      emerging views on the performance of teaching hospitals and to analyze how these
      views vary among hospital stakeholders. We conducted an in-depth case study of a
      TH using a quantitative survey method. The survey uses a questionnaire based on
      Parsons' social system action theory, which embraces the major models of
      organizational performance and covers three groups of internal stakeholders:
      physicians, caregivers and administrative staff. The questionnaires were
      distributed between April and September 2011. The results confirm that hospital
      performance is multifaceted and includes the dimensions of efficiency,
      effectiveness and quality of care, as well as organizational and human features.
      There is a high degree of consensus among all observed stakeholder groups about
      these values, and a shared view of performance is emerging. Our research provides
      useful information for defining management priorities to improve the performance
      of THs. 

PMID- 24560231
TI  - Exerting control and adapting to loss in amyotrophic lateral sclerosis.
AB  - People with amyotrophic lateral sclerosis (ALS) engage with a broad range of
      health care services from symptom onset to end-of-life care. We undertook a
      grounded theory study to identify processes that underpin how and why people with
      ALS engage with health care services. Using theoretical sampling procedures, we
      sampled 34 people from the Irish ALS population-based register during September
      2011 to August 2012. We conducted in-depth interviews with participants about
      their experiences of health care services. Our study yielded new insights into
      how people with ALS engage with services and adapt to loss. People with ALS live
      with insurmountable loss and never regain what they have already lost. Loss for
      people with ALS is multidimensional and includes loss of control. The experience
      of loss of control prompts people with ALS to search for control over health care
      services but exerting control in health care services can also include rendering
      control to service providers. People with ALS negotiate loss by exerting control
      over and rendering control to health care services. Our findings are important
      for future research that is attuned to how people with terminal illness exert
      control in health care services and make decisions about care in the context of
      mounting loss. 

PMID- 24560229
TI  - Do post-migration perceptions of social mobility matter for Latino immigrant
      health?
AB  - Latino immigrants exhibit health declines with increasing duration in the United
      States, which some attribute to a loss in social status after migration or
      downward social mobility. Yet, research into the distribution of perceived social
      mobility and patterned associations to Latino health is sparse, despite extensive
      research to show that economic and social advancement is a key driver of
      voluntary migration. We investigated Latino immigrant sub-ethnic group variation
      in the distribution of perceived social mobility, defined as the difference
      between respondents' perceived social status of origin had they remained in their
      country of origin and their current social status in the U.S. We also examined
      the association between perceived social mobility and past-year major depressive
      episode (MDE) and self-rated fair/poor physical health, and whether Latino sub
      ethnicity moderated these associations. We computed weighted logistic regression
      analyses using the Latino immigrant subsample (N=1561) of the National Latino and
      Asian American Study. Puerto Rican migrants were more likely to perceive downward
      social mobility relative to Mexican and Cuban immigrants who were more likely to
      perceive upward social mobility. Perceived downward social mobility was
      associated with increased odds of fair/poor physical health and MDE. Latino sub
      ethnicity was a statistically significant moderator, such that perceived downward
      social mobility was associated with higher odds of MDE only among Puerto Rican
      and Other Latino immigrants. In contrast, perceived upward social mobility was
      not associated with self-rated fair/poor physical health. Our findings suggest
      that perceived downward social mobility might be an independent correlate of
      health among Latino immigrants, and might help explain Latino sub-ethnic group
      differences in mental health status. Future studies on Latino immigrant health
      should use prospective designs to examine the physiological and psychological
      costs associated with perceived changes in social status with integration into
      the U.S. mainland. 

PMID- 24560232
TI  - Creating the 'dis-ease' of high cholesterol: a sociology of diagnosis reception
      analysis.
AB  - Using a sociology of diagnosis approach, this paper discusses the implication of
      high cholesterol being promoted as a disease rather than a risk factor for
      cardiovascular diseases. Drawing on data collected during the spring/summer of
      2012 from 49 in-depth interviews with women over the age of forty concerned with
      high cholesterol in Ontario, Canada, I explore participants' understanding of the
      issue of high cholesterol as a disease. More specifically, I examine where blame
      and responsibility for high cholesterol are placed and if they vary by women's
      class background. My findings reveal that all the participants believed in and
      internalized the diagnosis of high cholesterol. However, the disease is blamed on
      'lifestyle choices', and individual responsibilities, while women's awareness of
      the social determinants of health varies by class. I argue the sense of urgency
      surrounding high cholesterol is worrisome and the sole focus on lifestyle choice
      as both the cause and solution to high cholesterol is problematic for three
      reasons: it assumes that individual responsibility is adequate; it minimizes the
      socioeconomic constraints women face on a daily basis; and it reinforces the idea
      that individuals can be blamed for their health problems. 

PMID- 24560234
TI  - From sickness to badness: the criminalization of HIV in Michigan.
AB  - Sociological approaches to the social control of sickness have tended to focus on
      medicalization or the process through which social phenomena come to be regulated
      by medicine. Much less is known about how social problems historically understood
      as medical come to be governed by the criminal law, or what I term the
      "criminalization of sickness." Thirty three US states have enacted criminal
      statutes that require all HIV-positive individuals to disclose their infection
      before engaging in a wide range of sexual practices. Drawing on evidence from 58
      felony nondisclosure convictions in Michigan (95% of all convictions between 1992
      and 2010), I argue that the enforcement of the state's HIV disclosure law is not
      driven by medical concerns or public health considerations. Rather, it reflects
      pervasive moralizing narratives that frame HIV as a moral infection requiring
      interdiction and punishment. 

PMID- 24560233
TI  - The long lasting effects of education on old age health: evidence of gender
      differences.
AB  - The large and positive association between education and many health outcomes is
      well-documented but what drives this association is still a matter of discussion
      in the literature. Exploiting the time and geographical exogenous variation in
      compulsory schooling laws across 6 European countries this paper shows evidence
      of large and positive effects of the additional year of schooling induced by
      these policies only on men's self reported health, depression and memory in old
      age. Furthermore, results suggest that these effects come mainly through an
      improvement in men's working conditions with small or no role played by income
      and health related behaviors. On the other hand, since women affected by
      compulsory school reforms show a very low labor force attachment, they do not
      show similar spillovers. These policies only have mixed effects on women's health
      related behaviors. In particular, affected women show a lower probability of
      being overweight, but also a higher probability of having ever smoked. 

PMID- 24560235
TI  - Short and long term improvements in quality of chronic care delivery predict
      program sustainability.
AB  - Empirical evidence on sustainability of programs that improve the quality of care
      delivery over time is lacking. Therefore, this study aims to identify the
      predictive role of short and long term improvements in quality of chronic care
      delivery on program sustainability. In this longitudinal study, professionals
      [2010 (T0): n=218, 55% response rate; 2011 (T1): n=300, 68% response rate; 2012
      (T2): n=265, 63% response rate] from 22 Dutch disease-management programs
      completed surveys assessing quality of care and program sustainability. Our study
      findings indicated that quality of chronic care delivery improved significantly
      in the first 2 years after implementation of the disease-management programs. At
      T1, overall quality, self-management support, delivery system design, and
      integration of chronic care components, as well as health care delivery and
      clinical information systems and decision support, had improved. At T2, overall
      quality again improved significantly, as did community linkages, delivery system
      design, clinical information systems, decision support and integration of chronic
      care components, and self-management support. Multilevel regression analysis
      revealed that quality of chronic care delivery at T0 (p<0.001) and quality
      changes in the first (p<0.001) and second (p<0.01) years predicted program
      sustainability. In conclusion this study showed that disease-management programs
      based on the chronic care model improved the quality of chronic care delivery
      over time and that short and long term changes in the quality of chronic care
      delivery predicted the sustainability of the projects. 

PMID- 24560236
TI  - The pharmaceuticalization of sexual risk: vaccine development and the new
      politics of cancer prevention.
AB  - Vaccine development is a core component of pharmaceutical industry activity and a
      key site for studying pharmaceuticalization processes. In recent decades, two so
      called cancer vaccines have entered the U.S. medical marketplace: a vaccine
      targeting hepatitis B virus (HBV) to prevent liver cancers and a vaccine
      targeting human papillomavirus (HPV) to prevent cervical and other cancers. These
      viruses are two of six sexually transmissible infectious agents (STIs) that are
      causally linked to the development of cancers; collectively they reference an
      expanding approach to apprehending cancer that focuses attention simultaneously
      "inward" toward biomolecular processes and "outward" toward risk behaviors,
      sexual practices, and lifestyles. This paper juxtaposes the cases of HBV and HPV
      and their vaccine trajectories to analyze how vaccines, like pharmaceuticals more
      generally, are emblematic of contemporary pharmaceuticalization processes. We
      argue that individualized risk, in this case sexual risk, is produced and treated
      by scientific claims of links between STIs and cancers and through pharmaceutical
      company and biomedical practices. Simultaneous processes of sexualization and
      pharmaceuticalization mark these cases. Our comparison demonstrates that these
      processes are not uniform, and that the production of risks, subjects, and bodies
      depends not only on the specificities of vaccine development but also on the
      broader political and cultural frames within which sexuality is understood. 

PMID- 24560237
TI  - Beta-trace protein in pediatric otitis media with effusion.
AB  - OBJECTIVES: The middle ear cleft connects by membranes to the inner ear and the
      subarachnoid space particularly in infants. In order to gain more insight about
      the permeability between the two compartments we quantified the concentration of
      beta-trace protein - a highly specific marker for CSF and perilymph but not for
      serum and mucosal effusion - in middle ear secretions from children with otitis
      media with effusion. METHODS: One-hundred and three patients were included and 93
      samples from secretory otitis media were collected during myringotomy or
      explorative tympanotomy. Thirty-eight patients of 103 had to be excluded (36.9%).
      Of the 93 collected samples from 65 subjects, 82 viscous samples were pre-diluted
      1:1 with tyloxapol. In spite of the attempt to pre-dilute the viscous samples, 30
      glue-like samples of 93 were not applicable for nephelometry. The final analysis
      was made on 63 samples of 52 subjects (median age 3 years) which were quantified
      for beta-trace protein using immunonephelometry. RESULTS: In 3/63 samples the
      beta-trace protein values were below the detection range (<0.2 mg/L) and in 1/63
      it was beyond with 18.3mg/L. The median beta-trace protein value for 59 samples
      within the measuring range was 2.4 mg/L, range 0.2-14.2. CONCLUSION: In pediatric
      middle ear effusions, the beta-trace protein concentration was found to have a
      high range compared to other body fluids from other studies. In other studies,
      the values for serum (0.59 mg/L) or mucosal secretion (0.003-0.12 mg/L) were
      lower and the values in CSF (18.4 mg/L) or perilymphatic fluid (23.5 mg/L) were
      highest. This finding might indicate a weak barrier between the cerebrospinal
      fluid space or inner ear fluid compartments on the one side and the tympanic
      cavity on the other side given the condition of otitis media with effusion. The
      detection of beta-trace protein might be important to assess the risk of
      impending complications.

PMID- 24560238
TI  - Why parents refuse newborn hearing screening and default on follow-up rescreening
      -a South African perspective.
AB  - OBJECTIVES: This study describes screen refusal and follow-up default
      characteristics together with caregiver reasons for screen refusal and follow-up
      default in two South African universal newborn hearing screening programs.
      METHODS: A retrospective record review of universal newborn hearing screening
      conducted at two hospitals (Hospital A n = 954 infants; Hospital B n = 2135) over
      a 31-33 month period. Otoacoustic emission screening was conducted with rescreen
      recommended within six weeks for a uni- or bilateral refer. Program efficacy was
      described according to coverage, referral and follow-up rates. A prospective
      telephonic interview with caregivers who declined the initial screen (n = 25) and
      who defaulted on follow-up (n = 25) constituted the next study component.
      Caregivers were randomly selected from the screening programs for a survey
      related to reasons for newborn hearing screening refusal and follow-up default.
      RESULTS: Screening coverage (89.3% Hospital A; 57.4% Hospital B), initial
      referral rates (11.6% Hospital A; 21.2% Hospital B) and follow-up return rates
      (56.1% Hospital A; 35.8% Hospital B) differed significantly between hospitals and
      were below benchmarks. The most frequent reasons for screen refusal were related
      to costs (72%), caregiver knowledge of newborn hearing screening (64%) and health
      care professional knowledge and team collaboration (16%). Almost all caregivers
      (96%) indicated that if costs had been included in the birthing package or
      covered by medical insurance they would have agreed to newborn hearing screening.
      Reasons for follow-up default were most commonly related to caregiver knowledge
      of newborn hearing screening (32%) and costs (28%). One in four caregivers (24%)
      defaulted on follow-up because they forgot to bring their infant for a rescreen.
      Only half of caregivers (48%) who defaulted on follow-up reported being aware of
      initial screen results while 60% reported being aware of the recommended follow
      up rescreen. CONCLUSION: Caregivers most commonly refused screening due to
      associated costs and mostly defaulted on follow-up due to an apparent lack of
      knowledge regarding initial screen outcome and recommendations made for follow
      up. Including NHS as a mandated birthing service is essential if coverage is to
      be increased, while reducing follow-up defaults requires proactive reminders and
      improved communication with caregivers.

PMID- 24560239
TI  - Nasal septal lipoma in a child: Pai syndrome or not?
AB  - Lipoma is the most common soft tissue mass in adults but it is uncommon in
      children. Nasal septal lipoma is an even more rare entity. In this report, a 12
      year-old girl was presented with congenital nasal septal lipoma. She had
      permanent partial nasal obstruction on her right side and disfigurement of her
      right upper lip. CT scan revealed a lipoma-like mass in the septum plus an
      additional incidental finding of an intracranial lipoma. Further workup with MRI
      demonstrated corpus callosum agenesis with interhemispheric lipoma. To remove the
      mass, septoplasty, nasal lipoma excision and nasal vestibule V-Y advancement flap
      were performed. To close the lip a rotational advancement flap was required. Our
      case seemed to be a variety of Pai syndrome. We recommend imaging of the central
      nervous system in newborns with congenital lipomas located in the craniofacial
      midline to rule out the Pai syndrome. 

PMID- 24560240
TI  - Retrospective analysis of tympanoplasty in children with cleft palate: a 22-year
      experience: I. Mesotympanic (non-cholesteatomatous) cases.
AB  - BACKGROUND: Contradictory data have been published on the outcomes of ear
      surgeries in cleft patients. OBJECTIVES: To investigate whether there are
      differences in the short and long term outcomes of tympanoplasty performed due to
      childhood chronic mesotympanic otitis media in patients without and with cleft
      palate. SETTING: Tertiary care pediatric medical centre. METHODS: The authors
      retrospectively analysed the first author's data on pediatric tympanoplasties of
      the past 22 years with the help of a computer programme developed by the third
      author. The outcomes of 159 'NoCleft' tympanoplasties (119 patients, 144 ears)
      were compared to the outcomes of 31 'Cleft' tympanoplasties (21 patients, 27
      ears) with the average age of the patients being 10.8 and 10.7 years accordingly.
      RESULTS: The preoperative ABG (28.76/28.94dB, p = 0.468), the best postoperative
      ABG (12.78/10.04dB, p = 0.096), the last postoperative ABG (15.59/13.19dB, p =
      0.192), the final hearing gain (13.17/15.75dB, p = 0.253) and the postoperative
      ABG deterioration associated with time (2.81/3.15dB, p = 0.376) were
      statistically compared in the 'NoCleft'/'Cleft' groups. No significant difference
      was found between the outcomes of the two groups. The same parameters were
      examined separately after tympanoplasties performed with intact ossicular chain
      and after those requiring columella ossiculoplasty. The 'Cleft' group did not
      have worse outcomes in this respect, either. The average follow-up period of the
      patients was more than 3 years in both groups. The graft take rate was 100%,
      reperforation occurred in 3.5% of the cases in both groups. In their study,
      grommet insertion was more likely to be necessary in the 'Cleft' group.
      CONCLUSION: The authors concluded that there was no significant difference
      between the expectable outcomes of pediatric tympanoplasties in patients with and
      without cleft palate regarding mesotympanic cases; therefore, the indications for
      tympanoplasty are the same in the two groups. They outline the importance of the
      therapeutic management of cleft patients in the frameworks of a "Cleft Palate
      Team" and the necessity for their lifelong otorhinolaryngological care due to
      their vulnerable Eustachian tube function. They are planning to publish the same
      comparative analysis of their patients with cholesteatoma in a following study.

PMID- 24560241
TI  - Discussion.

PMID- 24560242
TI  - Novel temporary endovascular shunt technique to assist in situ fenestration for
      endovascular reconstruction of the distal aortic arch.
AB  - Thoracic endovascular aortic repair (TEVAR) of arch pathology presents special
      challenges for revascularization. To obtain an anatomic reconstruction of the
      arch arteries, in situ fenestration with extra-anatomic bypass has been
      increasingly used in TEVAR. We report a case involving TEVAR for a pseudoaneurysm
      at zone 2 of the thoracic aorta in a 37-year-old man with the use of in situ
      fenestration assisted by a temporary endovascular shunt technique. 

PMID- 24560243
TI  - Outcome after interposition of vein grafts for arterial repair of extremity
      injuries in civilians.
AB  - OBJECTIVE: The objective of this study was to report on immediate and long-term
      outcomes after vein graft interposition in patients with upper- and lower-limb
      arterial injuries. METHODS: In the retrospective data analysis, all patients who
      underwent vein graft repair of limb arterial injuries in our civilian institution
      since 1990 were included, analyzed, and followed. Study end points were crude
      early and long-term patency, vascular reintervention, limb salvage, and
      perioperative death. RESULTS: A total 152 consecutive patients (127 men; median
      age, 31.7 years; range, 5.3-77.2) who presented with 158 lesions of limb arteries
      (lower limb: n = 90; upper limb: n = 68) underwent repair with the use of vein
      graft interposition. The vast majority of lesions were caused by blunt trauma (n
      = 144; 91%). In early results, the 30-day mortality rate was 3.3%. In-hospital
      limb loss rate was significantly lower in the upper limb (n = 2; 2.9%) than in
      the lower limb (n = 12; 13.3%; P < .05). Primary early patency was 93% (upper
      limb) and 89% (lower limb): early graft occlusions occurred both in the upper
      limb (n = 5; 7%) and the lower limb (n = 10; 11%; P = .59). Occlusions were
      followed by amputation in six cases (upper limb: one of five; lower limb: five of
      10) despite successful revision of the occluded grafts. Long-term results after a
      median follow-up period of 6.0 years (range, 0.3-23.4) showed upper limb (62% of
      patients were followed): no late limb loss, no vascular reintervention; patency:
      97.6%; lower limb (66% of patients were followed): one late limb loss, one redo
      bypass for vein graft dilation, patency: 98.3%. CONCLUSIONS: Emergency repair of
      civilian artery injuries with the use of vein grafts is associated with
      considerable risk of early occlusion and limb loss. When compared with the upper
      limb, limb loss rate is significantly higher in the lower extremity. Early graft
      occlusion is frequently followed by limb loss, especially in the lower limb.
      During long-term follow-up, occlusions of interposed vein grafts, vascular
      reinterventions, and late amputations are uncommon.

PMID- 24560244
TI  - Aortic remodeling after endovascular treatment of complicated type B aortic
      dissection with the use of a composite device design.
AB  - OBJECTIVE: The purpose of this study is to report updated clinical and aortic
      remodeling results from the Study for the Treatment of complicated Type B Aortic
      Dissection using Endoluminal repair (STABLE) trial, a prospective, multicenter
      study evaluating safety and effectiveness of a pathology-specific endovascular
      system (proximal stent graft and distal bare metal stent) for the treatment of
      complicated type B aortic dissection. METHODS: All 86 enrolled patients (mean
      age, 59 years; 73.3% men) were treated within 90 days of symptom onset (55 with
      acute dissections and 31 with nonacute dissections). Inclusion criteria were
      branch vessel obstruction/compromise, impending rupture as evidenced by
      periaortic effusion/hematoma, resistant hypertension, persistent pain/symptoms,
      or aortic growth >=5 mm within 3 months (or transaortic diameter >=40 mm).
      Remodeling of the dissected aorta, including thrombosis of the false lumen and
      changes in the true lumen, false lumen, and transaortic diameter, were assessed
      in patients with available computed tomographic imaging through 2 years. RESULTS:
      The 30-day mortality rate was 4.7% (4/86) in the overall patient group (5.5% in
      acute patients and 3.2% in non-acute patients). Freedom from all-cause mortality
      was 88.3% at 1 year and 84.7% at 2 years (no significant difference between acute
      and nonacute patients). From baseline to 2 years, the true lumen diameter
      increased significantly in the descending thoracic aorta and the more distal
      abdominal aorta, along with a decrease in the false lumen diameter in both aortic
      segments. A majority of patients had either a stable or shrinking transaortic
      diameter in the thoracic (80.3% at 1 year and 73.9% at 2 years) or abdominal
      aorta (79.1% at 1 year and 66.7% at 2 years). Transaortic growth (>5 mm) occurred
      predominantly in acute dissections. Consistently, a shorter time from symptom
      onset to treatment was found to predict transaortic growth in the abdominal aorta
      (P = .03). CONCLUSIONS: Endovascular repair of complicated type B aortic
      dissection with the use of a composite construct demonstrates favorable early
      clinical outcomes and aortic remodeling. However, patients treated in the acute
      setting may be prone to aortic growth and may require close observation. Follow
      up through 5 years is ongoing.

PMID- 24560245
TI  - Restenosis after carotid artery stenting using a specific designed
      ultrasonographic protocol.
AB  - BACKGROUND: Nowadays, the number of patients undergoing carotid artery stenting
      (CAS) is increasing rapidly, and these patients require follow-up to monitor the
      patency of the device and the potential development of an in-stent restenosis
      (ISR). METHODS: Patients undergoing CAS at our institution underwent duplex
      ultrasound (DUS) at 6 months, 12 months, and yearly thereafter, using a
      prespecified protocol. Restenosis was defined as a more than 50% diameter
      reducing stenosis. Patients with DUS-diagnosed restenosis underwent carotid
      computerized tomography angiography (CTA) to confirm the presence of ISR. The
      frequency of restenosis was calculated by Kaplan-Meier survival estimates and was
      compared during a 2-year follow-up period. Interactions between restenosis and
      baseline variables were assessed using odds ratio. RESULTS: Between August 2007
      and March 2012 were performed 100 procedures in 96 patients, with a median age of
      72.9 years. The mean duration of follow-up was 29.2 months (+/-8.4). Restenosis
      occurred in 6 carotid arteries. The Kaplan-Meier estimate for the frequency of
      restenosis in 2 years was 6.0% and for severe restenosis was 3.0%. There were no
      occlusions. Diabetic patients seem to have a higher risk of ISR (OR=3.23, 95% CI
      .55-18.9). Carotid CTA was in agreement with the degree of stenosis estimated by
      DUS in all cases. CONCLUSIONS: Our results, using a DUS protocol and a specific
      peak systolic velocity threshold, showed that the frequency of restenosis at 2
      years after CAS is 6.0% and so that CAS is probably a durable revascularization
      procedure. We emphasize the diagnostic agreement achieved between DUS and carotid
      CTA.

PMID- 24560246
TI  - Safety evaluation of substituting clopidogrel for ticlopidine in Japanese
      patients with ischemic stroke--Hiroshima ticlopidine, clopidogrel safe exchange
      trial.
AB  - BACKGROUND: Clopidogrel is sometimes substituted for ticlopidine when
      cerebrovascular or cardiovascular patients develop hematologic abnormalities
      after ticlopidine treatment. However, the adverse event rate after the
      substitution to clopidogrel remains undetermined. Therefore, in this study, we
      aimed to define the risk of adverse events after substituting clopidogrel for
      ticlopidine without a washout period. METHODS: We prospectively enrolled patients
      older than 20 years who had a history of noncardioembolic strokes, including
      transient ischemic attacks, were treated with ticlopidine for at least 6 months.
      This study was conducted from August 26, 2008, when the first patient was
      enrolled, to January 16, 2012, the date of the last patient examination, at 8
      active stroke centers in Hiroshima, Japan. We excluded patients who had severe
      disabilities, evidence of cardioembolic stroke, or history of a bleeding event.
      Each patient received clopidogrel (either 50 mg or 75 mg) once a day in place of
      ticlopidine without a washout period. Follow-up exams were scheduled within 12
      months after the medication substitution. The primary end point of this study was
      adverse events of interest, including clinically significant reduced blood cell
      counts, hepatic dysfunction, bleeding, and other serious side effects. RESULTS:
      In this study, 110 patients were enrolled and analyzed in an intent-to-treat
      manner (modified intent to treat). Within the scheduled follow-up periods, 9
      primary end point events were observed in separate patients. The primary end
      point events were observed at a rate of 8.4% per year (Kaplan-Meier method). At
      the time of enrolment, 16 patients met the exclusion criteria, of which 8
      recovered from their abnormal hematologic results to the institutional normal
      limit after the substitution of ticlopidine for clopidogrel (57.4% per year).
      CONCLUSIONS: The adverse event rates after the substitution of ticlopidine for
      clopidogrel is similar to the adverse event rates of patients who were initially
      treated with clopidogrel. The substitution of clopidogrel for ticlopidine should
      be considered for patients who develop hematologic abnormalities from ticlopidine
      treatment.

PMID- 24560247
TI  - Intracranial arterial calcification can predict early vascular events after acute
      ischemic stroke.
AB  - BACKGROUND: Intracranial arterial calcification (IAC) is an evidence of advanced
      atherosclerosis. This study was aimed to investigate whether IAC predicts early
      vascular events (EVEs) during acute period of ischemic stroke. METHODS: We
      prospectively enrolled consecutive patients with acute ischemic stroke and
      transient ischemic attack within 48 hours from January 2005 to October 2012.
      Three IAC categories were defined according to the total IAC score as follows: no
      IAC (0 point), mild IAC (1-2 points), and severe IAC (>=3 points). EVEs included
      early progression/recurrence of stroke, coronary events, and vascular deaths
      within 2 weeks from stroke onset. We used multivariable Cox regression analyses
      to determine the effect of IAC on EVE. RESULTS: In the trend analysis of 1017
      total patients, there were significant trends of increased IAC toward higher
      total EVEs (10.5% versus 13.8% versus 21.2%, P < .001). Severe IAC was related to
      increased rate of early progression/recurrence (hazard ratio [HR] 2.00; 95%
      confidence interval [CI] 1.07-3.71, P = .029) and coronary events (HR 3.51; 95%
      CI 1.00-12.31, P = .050) but did not show an association for mortality (HR .54;
      95% CI .19-1.53, P = .224). Increased IAC was also related to a poor functional
      outcome after 3 months (odds ratio 2.23; 95% CI 1.38-3.59). CONCLUSIONS: IAC was
      significantly associated with increased early progression/recurrence of stroke
      and coronary events during acute period of ischemic stroke. IAC on the initial
      brain computed tomography would be used as a predictor for recurrent vascular
      events after acute ischemic stroke before further angiographic evaluation.

PMID- 24560248
TI  - Cerebral microbleeds in nonlacunar brain infarction are associated with lower
      coated-platelet levels.
AB  - BACKGROUND: Coated-platelets are a subset of platelets with high procoagulant
      potential observed on dual-agonist stimulation with collagen and thrombin. Coated
      platelet levels are elevated in patients with nonlacunar ischemic stroke compared
      with controls, although the presence of early hemorrhagic transformation is
      associated with lower coated-platelet levels. In contrast to infarction, patients
      with spontaneous intracerebral hemorrhage have lower coated-platelet levels, and
      these levels inversely correlate with bleed size. Cerebral microbleeds (CMBs)
      represent previous small hemorrhagic occurrences. We undertook a pilot study to
      investigate coated-platelet production and the presence of CMBs in patients with
      nonlacunar ischemic stroke. METHODS: Coated-platelet levels were determined in
      110 consecutive patients with a diagnosis of nonlacunar stroke. Microbleeds were
      identified using the published criteria by an experienced stroke neurologist.
      Coated-platelet levels were compared statistically between patients with and
      without CMBs using the nonparametric Wilcoxon rank sum test. RESULTS: Coated
      platelet levels (median [interquartile range]) for all patients were 44.1% [34%
      51.2%]. CMBs were detected in 22 patients (20%); these patients had significantly
      lower coated-platelet levels compared with those without CMBs (35.6% [22.6%
      47.2%] versus 45.1% [36.1%-51.5%]; P = .025), whereas other demographic and
      clinical factors did not differ significantly. CONCLUSIONS: The presence of CMBs
      in patients with nonlacunar ischemic stroke is associated with lower levels of
      coated-platelets. Larger prospective studies are needed to better establish the
      potential connection between altered coated-platelet synthesis, microbleeds,
      cerebral infarction, and possible hemorrhage-prone vascular changes.

PMID- 24560249
TI  - "No turn back approach" to reduce treatment time for endovascular treatment of
      acute ischemic stroke.
AB  - BACKGROUND: A delay in endovascular treatment is less likely if acute ischemic
      stroke patients proceed from emergency department (ED) to computed tomographic
      (CT) scanner and directly to angiographic suite (no turn back approach). We
      determined the feasibility of the "no turn back approach" and its effect on
      treatment times and patient outcomes. METHODS: The primary outcomes were
      procedures performed with a time interval: (1) between ED arrival and
      microcatheter placement of less than 120 minutes and (2) between CT scan
      acquisition and microcatheter placement of less than 90 minutes. We determined
      the effect of the no turn back approach on favorable outcome at discharge.
      RESULTS: There was a significantly higher rate of CT scan acquisition and
      microcatheter placement time of less than 90 minutes in patients in whom no turn
      back approach was used (57.6% versus 31.6%, P = .0007). There was a significantly
      higher rate of ED arrival to microcatheter placement time of less than 120
      minutes in patients in whom no turn back approach was used (31.8% versus 13.7%, P
      = .004). In the exploratory analysis, there was a trend toward higher rate of
      favorable outcomes (odds ratio 1.6, 95% confidence interval .9-2.8, P = .07)
      among those treated with no turn back approach after adjusting for age, admission
      National Institutes of Health Stroke Scale score strata, congestive heart
      failure, and diabetes mellitus. CONCLUSIONS: The no turn back approach appeared
      to be feasible and reduced the time interval between ED arrival and microcatheter
      placement in acute ischemic stroke patients undergoing endovascular treatment.

PMID- 24560251
TI  - Recurrent ischemic stroke in a patient with the Trousseau syndrome treated with
      dabigatran.
AB  - A 70-year-old man with multiple ischemic strokes was diagnosed with cardiac
      embolism and treated with dabigatran. Three months later, he suddenly developed
      vertigo and vomiting. Magnetic resonance imaging, showed recurrent lesions and
      blood tests revealed hypercoagulability, hypoproteinemia, and elevated
      cytokeratin 19 fragments that serve as a tumor marker of lung cancer. Chest
      computed tomography showed there were small nodules in bilateral lungs and
      swollen mediastinal lymph nodes. A conclusive diagnosis was impossible because
      the patient declined invasive procedures. We suspected primary lung cancer and
      diagnosed concomitant arterial thrombosis. We initially administered low
      molecular-weight heparin, which we later changed to vitamin K antagonist.
      Although stroke did not recur thereafter, liver metastasis resulted in death 6
      months later. The effectiveness of novel oral anticoagulants for preventing the
      Trousseau syndrome remains unclear. Further study is needed to prevent venous and
      arterial thromboses arising from the Trousseau syndrome. 

PMID- 24560250
TI  - Current status of recanalization therapy in acute ischemic stroke with
      symptomatic intracranial arterial occlusion in Korea.
AB  - BACKGROUND: Recent methodological advances in recanalization therapy may alter
      recanalization strategies and clinical outcomes in patients with symptomatic
      occlusion of intracranial cerebral arteries. However, few studies have analyzed
      these changes at a national level, with none conducted in Korea. METHODS: On the
      basis of a prospective multicenter stroke registry database in Korea, 642
      consecutive patients hospitalized within 12 hours of the onset with symptomatic
      occlusion of intracranial major cerebral arteries between March 2010 and November
      2011 were identified. Recanalization therapy was used in 48% (n = 307) of
      patients; intravenous thrombolysis only (IVT) in 46%, intra-arterial thrombolysis
      only (IAT) in 16%, and combined thrombolysis (CMT) in 38%. Of the 166 patients
      treated by IAT or CMT, the Penumbra system or the Solitaire was used in 58% of
      patients. RESULTS: Early neurologic improvement (ENI), 3-month modified Rankin
      scale (mRS) score of 2 or less, and symptomatic hemorrhagic transformation (SHT)
      were observed in 43%, 39%, and 9% of the patients in the IVT group; 52%, 27%, and
      12% of the patients in the IAT group; and 54%, 39%, and 12% of the patients in
      the CMT group, respectively. Compared with no treatment, adjusted odd ratios (95%
      confidence intervals) of recanalization therapy were 1.59 (1.04-2.42) for ENI,
      1.37 (.81-2.30) for 3-month mRS score of 2 or less, and 2.58 (1.12-5.91) for SHT.
      CONCLUSIONS: The variety and active use of endovascular approaches were quite
      noticeable. As a whole, recanalization therapy tended to contribute to favorable
      outcomes despite a significant increase of symptomatic hemorrhage.

PMID- 24560252
TI  - Health in global context; beyond the social determinants of health?
AB  - The rise of the social determinants of health (SDH) discourse on the basis of
      statistical evidence that correlates ill health to SDH and pictures causal
      pathways in comprehensive theoretical frameworks led to widespread awareness that
      health and health disparities are the outcome of complex pathways of
      interconnecting SDH. In this paper we explore whether and how SDH frameworks can
      be translated to effectively inform particular national health policies. To this
      end we identified major challenges for this translation followed by reflections
      on ways to overcome them. Most important challenges affecting adequate
      translation of these frameworks into concrete policy and intervention are 1)
      overcoming the inclination to conceptualize SDH as mere barriers to health
      behavior to be modified by lifestyle interventions by addressing them as
      structural factors instead; 2) obtaining sufficient in-depth insight in and
      evidence for the exact nature of the relationship between SDs and health; 3) to
      adequately translate the general determinants and pathways into explanations for
      ill health and limited access to health care in local settings; 4) to develop and
      implement policies and other interventions that are adjusted to those local
      circumstances. We conclude that to transform generic SDH models into useful
      policy tools and to prevent them to transform in SDH themselves, in depth
      understanding of the unique interplay between local, national and global SDH in a
      local setting, gathered by ethnographic research, is needed to be able to address
      structural SD in the local setting and decrease health inequity. 

PMID- 24560253
TI  - Reducing visual deficits caused by refractive errors in school and preschool
      children: results of a pilot school program in the Andean region of Apurimac,
      Peru.
AB  - BACKGROUND: Refractive error is defined as the inability of the eye to bring
      parallel rays of light into focus on the retina, resulting in nearsightedness
      (myopia), farsightedness (Hyperopia) or astigmatism. Uncorrected refractive error
      in children is associated with increased morbidity and reduced educational
      opportunities. Vision screening (VS) is a method for identifying children with
      visual impairment or eye conditions likely to lead to visual impairment.
      OBJECTIVE: To analyze the utility of vision screening conducted by teachers and
      to contribute to a better estimation of the prevalence of childhood refractive
      errors in Apurimac, Peru. Design : A pilot vision screening program in preschool
      (Group I) and elementary school children (Group II) was conducted with the
      participation of 26 trained teachers. Children whose visual acuity was<6/9
      [20/30] (Group I) and <= 6/9 (Group II) in one or both eyes, measured with the
      Snellen Tumbling E chart at 6 m, were referred for a comprehensive eye exam.
      Specificity and positive predictive value to detect refractive error were
      calculated against clinical examination. Program assessment with participants was
      conducted to evaluate outcomes and procedures. RESULTS: A total sample of 364
      children aged 3-11 were screened; 45 children were examined at Centro
      Oftalmologico Monsenor Enrique Pelach (COMEP) Eye Hospital. Prevalence of
      refractive error was 6.2% (Group I) and 6.9% (Group II); specificity of teacher
      vision screening was 95.8% and 93.0%, while positive predictive value was 59.1%
      and 47.8% for each group, respectively. Aspects highlighted to improve the
      program included extending training, increasing parental involvement, and helping
      referred children to attend the hospital. CONCLUSION: Prevalence of refractive
      error in children is significant in the region. Vision screening performed by
      trained teachers is a valid intervention for early detection of refractive error,
      including screening of preschool children. Program sustainability and
      improvements in education and quality of life resulting from childhood vision
      screening require further research.

PMID- 24560254
TI  - Anemia and malnutrition in indigenous children and adolescents of the Peruvian
      Amazon in a context of lead exposure: a cross-sectional study.
AB  - BACKGROUND: Indigenous children and adolescents of the Peruvian Amazon live in
      precarious conditions that could increase the risk of malnutrition. A particular
      problem in the Corrientes river communities is the high exposure to lead among
      children and adolescents. OBJECTIVE: This study aimed to determine the
      nutritional status of children and adolescents in indigenous communities in the
      Corrientes river basin and examine risk factors for anemia, stunting,
      underweight, and wasting. DESIGN: This was a cross-sectional assessment in
      children and adolescents aged 0-17 years from six communities (n=330). Data
      collection included measurement of hemoglobin levels, anthropometrics, blood lead
      levels (BLLs); a parental questionnaire including demographic and dwelling
      information; parents' occupation; and the child's duration of breastfeeding and
      food consumption. Analysis included univariate, bivariate, and logistic
      regression. RESULTS: Overall, anemia prevalence was 51.0%, stunting (proxy for
      chronic malnutrition) 50.0%, and underweight 20.0%. Bivariate analysis showed
      that anemia and underweight prevalence was higher in the 0-4 years group
      (p<0.05). No association was found between anemia, stunting, or underweight with
      gender, community exposure to oil activity, or consumption of river water.
      Stunting prevalence was higher in the group whose BLLs were >5 ug/dL (p<0.05). In
      the logistic regression analysis, no variable was associated with anemia or
      underweight. The group 5-11 years and >12 years had 1.9 and 3.1 times higher risk
      of stunting than the group under five years, respectively. Children and
      adolescents with BLLs >5 ug/dL had twice the risk of stunting compared to those
      with lower BLLs. CONCLUSIONS: Half of the study population was found with anemia
      and stunting. Anemia was more prevalent in the 0- to 5-year age group and
      stunting in the 12- to 17-year group. The association between stunting and BLLs
      might be attributed to a direct effect of lead on human growth. Also, poor
      nutrition and other socioeconomic-related factors may contribute to the
      simultaneous existence of stunting and elevated BLLs.

PMID- 24560255
TI  - Development of a clinical scoring system for assessment of immunosuppression in
      patients with tuberculosis and HIV infection without access to CD4 cell testing-
      results from a cross-sectional study in Ethiopia.
AB  - BACKGROUND: Currently, antiretroviral therapy (ART) is recommended for all HIV
      positive patients with tuberculosis (TB). The timing of ART during the course of
      anti-TB treatment is based on CD4 cell counts. Access to CD4 cell testing is not
      universally available; this constitutes an obstacle for the provision of ART in
      low-income countries. OBJECTIVE: To determine clinical variables associated with
      HIV co-infection in TB patients and to identify correlations between clinical
      variables and CD4 cell strata in HIV/TB co-infected subjects, with the aim of
      developing a clinical scoring system for the assessment of immunosuppression.
      DESIGN: Cross-sectional study of adults with TB (with and without HIV co
      infection) recruited in Ethiopian outpatient clinics. Clinical variables
      potentially associated with immunosuppression were recorded using a structured
      questionnaire, and they were correlated to CD4 cell strata used to determine
      timing of ART initiation. Variables found to be significant in multivariate
      analysis were used to construct a scoring system. Results : Among 1,116
      participants, the following findings were significantly more frequent in 307 HIV
      positive patients compared to 809 HIV-negative subjects: diarrhea, odynophagia,
      conjunctival pallor, herpes zoster, oral candidiasis, skin rash, and mid-upper
      arm circumference (MUAC) <20 cm. Among HIV-positive patients, conjunctival
      pallor, MUAC <20 cm, dyspnea, oral hairy leukoplakia (OHL), oral candidiasis, and
      gingivitis were significantly associated with <350 CD4 cells/mm(3). A scoring
      system based on these variables had a negative predictive value of 87% for
      excluding subjects with CD4 cell counts <100 cells/mm(3); however, the positive
      predictive value for identifying such individuals was low (47%). CONCLUSIONS:
      Clinical variables correlate with CD4 cell strata in HIV-positive patients with
      TB. The clinical scoring system had adequate negative predictive value for
      excluding severe immunosuppression. Clinical scoring systems could be of use to
      categorize TB/HIV co-infected patients with regard to the timing of ART
      initiation in settings with limited access to laboratory facilities.

PMID- 24560256
TI  - The association between insurance status and in-hospital mortality on the public
      medical wards of a Kenyan referral hospital.
AB  - BACKGROUND: Observational data in the United States suggests that those without
      health insurance have a higher mortality and worse health outcomes. A linkage
      between insurance coverage and outcomes in hospitalized patients has yet to be
      demonstrated in resource-poor settings. METHODS: To determine whether uninsured
      patients admitted to the public medical wards at a Kenyan referral hospital have
      any difference in in-hospital mortality rates compared to patients with
      insurance, we performed a retrospective observational study of all inpatients
      discharged from the public medical wards at Moi Teaching and Referral Hospital in
      Eldoret, Kenya, over a 3-month study period from October through December 2012.
      The primary outcome of interest was in-hospital death, and the primary
      explanatory variable of interest was health insurance status. RESULTS: During the
      study period, 201 (21.3%) of 956 patients discharged had insurance. The National
      Hospital Insurance Fund was the only insurance scheme noted. Overall, 211
      patients (22.1%) died. The proportion who died was greater among the uninsured
      compared to the insured (24.7% vs. 11.4%, Chi-square = 15.6, p<0.001). This
      equates to an absolute risk reduction of 13.3% (95% CI 7.9-18.7%) and a relative
      risk reduction of 53.8% (95% CI 30.8-69.2%) of in-hospital mortality with
      insurance. After adjusting for comorbid illness, employment status, age, HIV
      status, and gender, the association between insurance status and mortality
      remained statistically significant (adjusted odds ratio (AOR) = 0.40, 95% CI 0.24
      0.66) and similar in magnitude to the association between HIV status and
      mortality (AOR = 2.45, 95% CI 1.56-3.86). CONCLUSIONS: Among adult patients
      hospitalized in a public referral hospital in Kenya, insurance coverage was
      associated with decreased in-hospital mortality. This association was comparable
      to the relationship between HIV and mortality. Extension of insurance coverage
      may yield substantial benefits for population health.

PMID- 24560257
TI  - Gender inequalities in health: exploring the contribution of living conditions in
      the intersection of social class.
AB  - BACKGROUND: Women experience poorer health than men despite their longer life
      expectancy, due to a higher prevalence of non-fatal chronic illnesses. This paper
      aims to explore whether the unequal gender distribution of roles and resources
      can account for inequalities in general self-rated health (SRH) by gender, across
      social classes, in a Southern European population. METHODS: Cross-sectional study
      of residents in Catalonia aged 25-64, using data from the 2006 population living
      conditions survey (n=5,817). Poisson regression models were used to calculate the
      fair/poor SRH prevalence ratio (PR) by gender and to estimate the contribution of
      variables assessing several dimensions of living conditions as the reduction in
      the PR after their inclusion in the model. Analyses were stratified by social
      class (non-manual and manual). RESULTS: SRH was poorer for women among both non
      manual (PR 1.39, 95% CI 1.09-1.76) and manual social classes (PR 1.36, 95% CI
      1.20-1.56). Adjustment for individual income alone eliminated the association
      between sex and SRH, especially among manual classes (PR 1.01, 95% CI 0.85-1.19;
      among non-manual 1.19, 0.92-1.54). The association was also reduced when
      adjusting by employment conditions among manual classes, and household material
      and economic situation, time in household chores and residential environment
      among non-manual classes. DISCUSSION: Gender inequalities in individual income
      appear to contribute largely to women's poorer health. Individual income may
      indicate the availability of economic resources, but also the history of access
      to the labour market and potentially the degree of independence and power within
      the household. Policies to facilitate women's labour market participation, to
      close the gender pay gap, or to raise non-contributory pensions may be helpful to
      improve women's health.

PMID- 24560258
TI  - The global health concept of the German government: strengths, weaknesses, and
      opportunities.
AB  - Recognising global health as a rapidly emerging policy field, the German federal
      government recently released a national concept note for global health politics
      (July 10, 2013). As the German government could have a significant impact on
      health globally by making a coherent, evidence-informed, and long-term commitment
      in this field, we offer an initial appraisal of the strengths, weaknesses, and
      opportunities for development recognised in this document. We conclude that the
      national concept is an important first step towards the implementation of a
      coherent global health policy. However, important gaps were identified in the
      areas of intellectual property rights and access to medicines. In addition,
      global health determinants such as trade, economic crises, and liberalisation as
      well as European Union issues such as the health of migrants, refugees, and
      asylum seekers are not adequately addressed. Furthermore, little information is
      provided about the establishment of instruments to ensure an effective inter
      ministerial cooperation. Finally, because implementation aspects for the national
      concept are critical for the success of this initiative, we call upon the newly
      elected 2013 German government to formulate a global health strategy, which
      includes a concrete plan of action, a time scale, and measurable goals. 

PMID- 24560259
TI  - A new governance space for health.
AB  - Global health refers to 'those health issues which transcend national boundaries
      and governments and call for actions on the global forces and global flows that
      determine the health of people'. (Kickbusch 2006) Governance in this trans
      national and cross-cutting arena can be analyzed along three political spaces:
      global health governance, global governance for health, and governance for global
      health. It is argued that the management of the interface between these three
      political spaces of governance in the global public health domain is becoming
      increasingly important in order to move the global health agenda forward. Global
      health governance refers mainly to those institutions and processes of governance
      which are related to an explicit health mandate, such as the World Health
      Organization; global governance for health refers mainly to those institutions
      and processes of global governance which have a direct and indirect health
      impact, such as the United Nations, World Trade Organization or the Human Rights
      Council; governance for global health refers to the institutions and mechanisms
      established at the national and regional level to contribute to global health
      governance and/or to governance for global health--such as national global health
      strategies or regional strategies for global health. It can also refer to club
      strategies, such as agreements by a group of countries such as the BRICS. In all
      three political spaces, the involvement of a multitude of state and non-state
      actors has become the norm--that is why issues of legitimacy, accountability and
      transparency have moved to the fore. The transnational nature of global health
      will require the engagement of all actors to produce global public goods for
      health (GPGH) and to ensure a rules-based and reliably financed global public
      health domain.

PMID- 24560260
TI  - Tracking aid flows for development assistance for health.
AB  - BACKGROUND AND OBJECTIVES: The global architecture for providing development
      assistance for health (DAH) has become increasing complex in the last decade,
      with many new funding agencies entering the health sector. This study presents a
      detailed picture of European Union (EU) and EU member state originating DAH
      between 2006 and 2009; with a specific focus on assessing the extent of
      complementarity of development assistance sourced from the EU. DESIGN: We use a
      combination of internal EU reporting systems, OECD-DAC creditor reporting system
      data and other data sources to estimate DAH flows. Our method uses a line by line
      project assessment in order to identify and categorise DAH flows. RESULTS AND
      CONCLUSIONS: Our findings show a complex picture of DAH flows--from source, to
      channel of assistance, to channel of implementation--that is hard to track at the
      global level, and rarely comprehensively and regularly tracked at the country
      level. While the majority of EU DAH is focused on low and lower middle income
      countries there also remains much disparity between countries; and further
      analysis is required to better understand whether these imbalances are fair and
      efficient; or result in overlap. We also recommend investment in quality control
      of DAH tracking internally within donor agencies, and investment in the
      development of country based systems in order to enable countries and development
      partners better harmonise DAH flows.

PMID- 24560261
TI  - Strengthening health systems by health sector reforms.
AB  - BACKGROUND: The rising burden of disease and weak health systems are being
      compounded by the persistent economic downturn, re-emerging diseases, and violent
      conflicts. There is a growing recognition that the global health agenda needs to
      shift from an emphasis on disease-specific approaches to strengthening of health
      systems, including dealing with social, environmental, and economic determinants
      through multisectoral responses. METHODS: A review and analysis of data on
      strengthening health sector reform and health systems was conducted. Attention
      was paid to the goal of health and interactions between health sector reforms and
      the functions of health systems. Further, we explored how these interactions
      contribute toward delivery of health services, equity, financial protection, and
      improved health. FINDINGS: Health sector reforms cannot be developed from a
      single global or regional policy formula. Any reform will depend on the country's
      history, values and culture, and the population's expectations. Some of the
      emerging ingredients that need to be explored are infusion of a health systems
      agenda; development of a comprehensive policy package for health sector reforms;
      improving alignment of planning and coordination; use of reliable data; engaging
      'street level' policy implementers; strengthening governance and leadership; and
      allowing a holistic and developmental approach to reforms. CONCLUSIONS: The
      process of reform needs a fundamental rather than merely an incremental and
      evolutionary change. Without radical structural and systemic changes, existing
      governance structures and management systems will continue to fail to address the
      existing health problems.

PMID- 24560262
TI  - Global health ethics: an introduction to prominent theories and relevant topics.
AB  - Global health ethics is a relatively new term that is used to conceptualize the
      process of applying moral value to health issues that are typically characterized
      by a global level effect or require action coordinated at a global level. It is
      important to acknowledge that this account of global health ethics takes a
      predominantly geographic approach and may infer that the subject relates
      primarily to macro-level health phenomena. However, global health ethics could
      alternatively be thought of as another branch of health ethics. It may then
      relate to specific topics in themselves, which might also include micro-level
      health phenomena. In its broadest sense, global health ethics is a normative
      project that is best characterized by the challenge of developing common values
      and universal norms for responding to global health threats. Consequently, many
      subjects fall within its scope. Whilst several accounts of global health ethics
      have been conceptualized in the literature, a concise demarcation of the paradigm
      is still needed. Through means of a literature review, this paper presents a two
      part introduction to global health ethics. First, the framework of 'borrowed'
      ethics that currently form the core of global health ethics is discussed in
      relation to two essential ethical considerations: 1) what is the moral
      significance of health and 2) what is the moral significance of boundaries?
      Second, a selection of exemplar ethical topics is presented to illustrate the
      range of topics within global health ethics. 

PMID- 24560263
TI  - Education for public health in Europe and its global outreach.
AB  - INTRODUCTION: At the present time, higher education institutions dealing with
      education for public health in Europe and beyond are faced with a complex and
      comprehensive task of responding to global health challenges. REVIEW: Literature
      reviews in public health and global health and exploration of internet
      presentations of regional and global organisations dealing with education for
      public health were the main methods employed in the work presented in this paper.
      Higher academic institutions are searching for appropriate strategies in
      competences-based education, which will increase the global attractiveness of
      their academic programmes and courses for continuous professional development.
      Academic professionals are taking advantage of blended learning and new web
      technologies. In Europe and beyond they are opening up debates about the scope of
      public health and global health. Nevertheless, global health is bringing
      revitalisation of public health education, which is recognised as one of the core
      components by many other academic institutions involved in global health work.
      More than ever, higher academic institutions for public health are recognising
      the importance of institutional partnerships with various organisations and
      efficient modes of cooperation in regional and global networks. Networking in a
      global setting is bringing new opportunities, but also opening debates about
      global harmonisation of competence-based education to achieve functional
      knowledge, increase mobility of public health professionals, better employability
      and affordable performance. CONCLUSIONS: As public health opportunities and
      threats are increasingly global, higher education institutions in Europe and in
      other regions have to look beyond national boundaries and participate in networks
      for education, research and practice.

PMID- 24560264
TI  - Global health in the European Union--a review from an agenda-setting perspective.
AB  - This review attempts to analyse the global health agenda-setting process in the
      European Union (EU). We give an overview of the European perspective on global
      health, making reference to the developments that led to the EU acknowledging its
      role as a global health actor. The article thereby focuses in particular on the
      European interpretation of its role in global health from 2010, which was
      formalised through, respectively, a European Commission Communication and
      European Council Conclusions. Departing from there, and based on Kingdon's
      multiple streams theory on agenda setting, we identify some barriers that seem to
      hinder the further establishment and promotion of a solid global health agenda in
      the EU. The main barriers for creating a strong European global health agenda are
      the fragmentation of the policy community and the lack of a common definition for
      global health in Europe. Forwarding the agenda in Europe for global health
      requires more clarification of the common goals and perspectives of the policy
      community and the use of arising windows of opportunity.

PMID- 24560265
TI  - The workforce for health in a globalized context--global shortages and
      international migration.
AB  - The 'crisis in human resources' in the health sector has been described as one of
      the most pressing global health issues of our time. The World Health Organization
      (WHO) estimates that the world faces a global shortage of almost 4.3 million
      doctors, midwives, nurses, and other healthcare professionals. A global
      undersupply of these threatens the quality and sustainability of health systems
      worldwide. This undersupply is concurrent with globalization and the resulting
      liberalization of markets, which allow health workers to offer their services in
      countries other than those of their origin. The opportunities of health workers
      to seek employment abroad has led to a complex migration pattern, characterized
      by a flow of health professionals from low- to high-income countries. This global
      migration pattern has sparked a broad international debate about the consequences
      for health systems worldwide, including questions about sustainability, justice,
      and global social accountabilities. This article provides a review of this
      phenomenon and gives an overview of the current scope of health workforce
      migration patterns. It further focuses on the scientific discourse regarding
      health workforce migration and its effects on both high- and low-income countries
      in an interdependent world. The article also reviews the internal and external
      factors that fuel health worker migration and illustrates how health workforce
      migration is a classic global health issue of our time. Accordingly, it
      elaborates on the international community's approach to solving the workforce
      crisis, focusing in particular on the WHO Code of Practice, established in 2010. 

PMID- 24560267
TI  - Global health in the 21st century.
AB  - INTRODUCTION: Since the end of the 1990s, globalization has become a common term,
      facilitated by the social media of today and the growing public awareness of life
      threatening problems common to all people, such as global warming, global
      security and global divides. REVIEW: For the main parameters of health like the
      burden of disease, life expectancy and healthy life expectancy, extreme
      discrepancies are observed across the world. Infant mortality, malnutrition and
      high fertility go hand in hand. Civil society, as an indispensable activator of
      public health development, mainly represented by non-governmental organisations
      (NGOs), is characterised by a high degree of fragmentation and lack of public
      accountability. The World Federation of Public Health Associations is used as an
      example of an NGO with a global mission and fostering regional cooperation as an
      indispensable intermediate level.The lack of a globally valid terminology of
      basic public health functions is prohibitive for coordinated global and regional
      efforts. Attempts to harmonise essential public health functions, services and
      operations are under way to facilitate communication and mutual understanding.
      RECOMMENDATIONS: 1) Given the limited effects of the Millennium Development Goal
      agenda, the Post-2015 Development Goals should focus on integrated regional
      development. 2) A code of conduct for NGOs should be urgently developed for the
      health sector, and NGOs should be registered and accredited. 3) The harmonisation
      of the basic terminology for global public health essentials should be enhanced.

PMID- 24560266
TI  - The missing link--the role of primary care in global health.
AB  - This chapter provides an overview of the role of primary care in the context of
      global health. Universal health coverage is a key priority for WHO and its member
      states, and provision of accessible and safe primary care is recognised as
      essential to meet this important international policy goal. Nevertheless, more
      than three decades after Alma Ata, the provision of primary health care remains
      inadequate, indicating that primary care has not received the priority it
      deserves, in many parts of the world. This is despite the proven health benefits
      that result from access to comprehensive primary health care. We highlight some
      examples of good practice and discuss the relevance of primary care in the
      context of health equity and cost-effectiveness. Challenges that influence the
      success of primary care include the availability of a qualified workforce,
      financing and system design and quality assurance and patient safety. 

PMID- 24560268
TI  - The Millennium Development Goals: experiences, achievements and what's next.
AB  - The Millennium Development Goals (MDGs) are eight international development goals
      to be achieved by 2015 addressing poverty, hunger, maternal and child mortality,
      communicable disease, education, gender inequality, environmental damage and the
      global partnership. Most activities worldwide have focused on maternal and child
      health and communicable diseases, while less attention has been paid to
      environmental sustainability and the development of a global partnership. Up to
      now, several targets have been at least partially achieved: hunger reduction is
      on track, poverty has been reduced by half, living conditions of 200 million
      deprived people enhanced, maternal and child mortality as well as communicable
      diseases diminished and education improved. Nevertheless, some goals will not be
      met, particularly in the poorest regions, due to different challenges (e.g. the
      lack of synergies among the goals, the economic crisis, etc.). The post-2015
      agenda is now under discussion. The new targets, whatever they will be called,
      should reflect today's political situation, health and environmental challenges,
      and an all-inclusive, intersectoral and accountable approach should be adopted. 

PMID- 24560269
TI  - Special issue "Facets of Global Health: Globalisation, Equity, Impact and
      Action". Preface.

PMID- 24560270
TI  - Too sweet for autophagy: hexokinase inhibition of mTORC1 activates autophagy.
AB  - In this issue, Roberts et al. (2014) describe how hexokinase and mTORC1 cooperate
      to sense disequilibrium between glucose uptake and utilization and direct the
      balance of anabolism and catabolism to ensure the appropriate use of cellular
      resources.

PMID- 24560271
TI  - Akt-ivation of RNA splicing.
AB  - Cells must tightly control alternative splicing of RNA to maintain homeostasis;
      in this issue of Molecular Cell, Sanidas et al. (2014) provide new insights into
      the regulation of RNA splicing by Akt isoforms through phosphorylation of histone
      modification machinery.

PMID- 24560272
TI  - Fine-tuning of DNA damage-dependent ubiquitination by OTUB2 supports the DNA
      repair pathway choice.
AB  - DNA double-strand breaks (DSBs) are deleterious lesions that lead to genetic
      mutations and cell death. Protein ubiquitination mediated by the E3 ubiquitin
      ligase RNF8 within the regions surrounding DSBs recruits DNA DSB response (DDR)
      factors and induces chromatin remodeling, which supports cell survival after DNA
      damage. Nevertheless, the impact of RNF8-mediated ubiquitination on DNA repair
      remains to be elucidated. Here, we report that depletion of the deubiquitinating
      enzyme OTUB2 enhances RNF8-mediated ubiquitination in an early phase of the DDR
      and promotes faster DSB repair but suppresses homologous recombination. The rapid
      ubiquitination results in accelerated accumulation of 53BP1 and RAP80 at DSBs,
      which in turn protects DSB ends from resection in OTUB2-depleted cells.
      Mechanistically, OTUB2 suppresses RNF8-mediated L3MBTL1 ubiquitination and Lys 63
      linked ubiquitin chain formation in a deubiquitinating activity-dependent manner.
      Thus, OTUB2 fine-tunes the speed of DSB-induced ubiquitination so that the
      appropriate DNA repair pathway is chosen.

PMID- 24560273
TI  - Replication origin selection regulates the distribution of meiotic recombination.
AB  - The program of DNA replication, defined by the temporal and spatial pattern of
      origin activation, is altered during development and in cancers. However, whether
      changes in origin usage play a role in regulating specific biological processes
      remains unknown. We investigated the consequences of modifying origin selection
      on meiosis in fission yeast. Genome-wide changes in the replication program of
      premeiotic S phase do not affect meiotic progression, indicating that meiosis
      neither activates nor requires a particular origin pattern. In contrast, local
      changes in origin efficiencies between different replication programs lead to
      changes in Rad51 recombination factor binding and recombination frequencies in
      these domains. We observed similar results for Rad51 when changes in efficiencies
      were generated by directly targeting expression of the Cdc45 replication factor.
      We conclude that origin selection is a key determinant for organizing meiotic
      recombination, providing evidence that genome-wide modifications in replication
      program can modulate cellular physiology.

PMID- 24560274
TI  - Double suppression of the Galpha protein activity by RGS proteins.
AB  - Regulator of G protein signaling (RGS) proteins accelerate GTP hydrolysis on G
      protein alpha subunits, restricting their activity downstream from G protein
      coupled receptors. Here we identify Drosophila Double hit (Dhit) as a dual RGS
      regulator of Galphao. In addition to the conventional GTPase-activating action,
      Dhit possesses the guanine nucleotide dissociation inhibitor (GDI) activity,
      slowing the rate of GTP uptake by Galphao; both activities are mediated by the
      same RGS domain. These findings are recapitulated using homologous mammalian
      Galphao/i proteins and RGS19. Crystal structure and mutagenesis studies provide
      clues into the molecular mechanism for this unprecedented GDI activity.
      Physiologically, we confirm this activity in Drosophila asymmetric cell divisions
      and HEK293T cells. We show that the oncogenic Galphao mutant found in breast
      cancer escapes this GDI regulation. Our studies identify Dhit and its homologs as
      double-action regulators, inhibiting Galphao/i proteins both through suppression
      of their activation and acceleration of their inactivation through the single RGS
      domain. 

PMID- 24560275
TI  - Increased ventricular pacing threshold levels in patients with high serum uric
      acid levels.
AB  - BACKGROUND: Permanent cardiac pacemakers (PCM) are accepted as the most effective
      treatment for symptomatic bradyarrhythmias. Serum uric acid (UA) levels are
      associated with various inflammatory markers, oxidative stress, and endothelial
      dysfunction. This study aimed to investigate the association between serum UA and
      ventricular pacing threshold (VPT) levels in patients who underwent permanent
      pacemaker implantation. MATERIALS AND METHODS: We retrospectively analyzed a
      total of 198 patients who underwent PCM implantation for indications such as
      symptomatic bradycardia without a reversible etiology and high-degree and
      complete atrioventricular block. RESULTS: VPT values were found to correlate with
      serum UA levels (r=0.591, p<0.001), high sensitivity C-reactive protein (hs-CRP)
      levels (r=0.505, p<0.001), and ventricular impedance (r=0.220, p=0.016). The
      serum UA levels and hs-CRP levels were also correlated (r=0.691, p<0.001). To
      identify independent risk factors for VPT values, a multivariate linear
      regression model was conducted, and serum UA levels (beta=0.361, p=0.001), hs-CRP
      levels (beta=0.277, p=0.012), and impedance values (beta=0.207, p=0.011) were
      found to be independent risk factors for VPT. CONCLUSION: In the present study,
      VPT values at the time of implantation and at the 30th day were increased in
      patients with high serum UA levels. To further extend the life of pacemakers, as
      well as other factors that affect threshold values, serum UA levels should be
      noted.

PMID- 24560276
TI  - Despeckle filtering software toolbox for ultrasound imaging of the common carotid
      artery.
AB  - Ultrasound imaging of the common carotid artery (CCA) is a non-invasive tool used
      in medicine to assess the severity of atherosclerosis and monitor its progression
      through time. It is also used in border detection and texture characterization of
      the atherosclerotic carotid plaque in the CCA, the identification and measurement
      of the intima-media thickness (IMT) and the lumen diameter that all are very
      important in the assessment of cardiovascular disease (CVD). Visual perception,
      however, is hindered by speckle, a multiplicative noise, that degrades the
      quality of ultrasound B-mode imaging. Noise reduction is therefore essential for
      improving the visual observation quality or as a pre-processing step for further
      automated analysis, such as image segmentation of the IMT and the atherosclerotic
      carotid plaque in ultrasound images. In order to facilitate this preprocessing
      step, we have developed in MATLAB((r)) a unified toolbox that integrates image
      despeckle filtering (IDF), texture analysis and image quality evaluation
      techniques to automate the pre-processing and complement the disease evaluation
      in ultrasound CCA images. The proposed software, is based on a graphical user
      interface (GUI) and incorporates image normalization, 10 different despeckle
      filtering techniques (DsFlsmv, DsFwiener, DsFlsminsc, DsFkuwahara, DsFgf,
      DsFmedian, DsFhmedian, DsFad, DsFnldif, DsFsrad), image intensity normalization,
      65 texture features, 15 quantitative image quality metrics and objective image
      quality evaluation. The software is publicly available in an executable form,
      which can be downloaded from http://www.cs.ucy.ac.cy/medinfo/. It was validated
      on 100 ultrasound images of the CCA, by comparing its results with quantitative
      visual analysis performed by a medical expert. It was observed that the despeckle
      filters DsFlsmv, and DsFhmedian improved image quality perception (based on the
      expert's assessment and the image texture and quality metrics). It is anticipated
      that the system could help the physician in the assessment of cardiovascular
      image analysis.

PMID- 24560277
TI  - Classification of intelligence quotient via brainwave sub-band power ratio
      features and artificial neural network.
AB  - This paper elaborates on the novel intelligence assessment method using the
      brainwave sub-band power ratio features. The study focuses only on the left
      hemisphere brainwave in its relaxed state. Distinct intelligence quotient groups
      have been established earlier from the score of the Raven Progressive Matrices.
      Sub-band power ratios are calculated from energy spectral density of theta, alpha
      and beta frequency bands. Synthetic data have been generated to increase dataset
      from 50 to 120. The features are used as input to the artificial neural network.
      Subsequently, the brain behaviour model has been developed using an artificial
      neural network that is trained with optimized learning rate, momentum constant
      and hidden nodes. Findings indicate that the distinct intelligence quotient
      groups can be classified from the brainwave sub-band power ratios with 100%
      training and 88.89% testing accuracies.

PMID- 24560278
TI  - The beneficial effects of rosuvastatin are independent of zinc supplementation in
      patients with atherosclerosis.
AB  - BACKGROUND: Statins have multiple antiatherosclerotic effects, but can reduce
      blood plasma concentrations of minerals, including zinc. As zinc possesses
      antiinflammatory and antioxidant effects, low zinc status can promote injuries or
      inadequate tissue repair in endothelial cells. Metallothionein (MT) expression
      might modulate responses induced by statins in patients with atherosclerosis.
      However, research regarding mineral status and the use of statins is scarce. This
      study evaluated the effects of zinc supplementation on zinc status and expression
      of the zinc-dependent MT1F and MT2A genes in patients with atherosclerosis
      treated with rosuvastatin. METHODS: A double-blind, randomized clinical trial was
      performed with 54 participants treated with 10mg rosuvastatin for 4 months with
      or without zinc supplementation (30mg/day). Diet, lipid profile, high-sensitivity
      reactive protein C (hs-CRP), plasma and erythrocyte zinc concentrations,
      erythrocyte superoxide dismutase (SOD) activity, and MT1F and MT2A genes
      expression were analyzed before and after intervention. RESULTS: Rosuvastatin
      therapy was effective in reducing low- and non-high-density lipoprotein, total
      cholesterol, triglycerides, and hs-CRP levels, independent of zinc
      supplementation. Additionally, zinc treatment had no effect on SOD enzyme
      activity (P=0.201), plasma (P>0.671) and erythrocyte (P>0.123) zinc
      concentrations, or the pattern of MT1F and MT2A genes expression (P=0.088 and
      P=0.229, respectively). CONCLUSIONS: The effectiveness of rosuvastatin treatment
      is independent of the effects of zinc supplementation. Moreover, rosuvastatin
      treatment did not have a significant impact on zinc status or MT1F and MT2A genes
      expression in patients with atherosclerosis.

PMID- 24560279
TI  - Trace analysis of hydrophobic micropollutants in aqueous samples using capillary
      traps.
AB  - Studying the fate of persistent organic pollutants (POPs) in glacier environments
      scientist face the challenge of snow and ice samples, in which concentrations of
      these pollutants are at the ultra-trace level and the amount of sample available
      is often very limited. We have improved an extraction method for hydrophobic
      organic pollutants such as polychlorinated biphenyls (PCBs) in aqueous media to
      meet the requirements of these challenging samples. It is based on partitioning
      of the analytes from the water into the polydimethylsiloxane (PDMS) coating of an
      open tubular-fused-silica capillary. By comparison with conventional liquid
      liquid extraction, we validated the method for six indicator PCBs, covering a
      wide range of polarity. The new method has very low detection limits of 10-20pg/L
      for the investigated PCBs, a small uncertainty between 9% and 37%, depending on
      concentration, and requires a small sample volume of less than one liter.
      Further, it is characterized by easy handling and reduced organic solvents
      consumption. The method is comparatively insensitive to contamination,
      reproducible, and suitable for a wide range of applications. 

PMID- 24560280
TI  - Assessment of genotoxicity and acute toxic effect of the imatinib mesylate in
      plant bioassays.
AB  - Imatinib mesylate (IM) is at present one of the most widely used cytostatic drugs
      in developed countries but information on its ecotoxicological activities is
      scarce. This article describes the results of the first investigation in which
      genotoxic and acute toxic properties of the drug were studied in higher plants.
      IM was tested in two widely used plant bioassays namely in micronucleus (MN)
      assays with meiotic tetrad cells of Tradescantia (clone #4430) and in mitotic
      root tip cells of Allium cepa. Additionally, acute toxic effects (inhibition of
      cell division and growth of roots) were monitored in the onions. Furthermore, we
      studied the impact of the drug on the fertility of higher plants in pollen
      abortion experiments with three wildlife species (Chelidonium majus, Tradescantia
      palludosa and Arabidopsis thaliana). In MN assays with Tradesacantia a
      significant effect was seen with doses ?10MUM; the Allium MN assay was even more
      sensitive (LOEL?1.0MUM). A significant decrease of the mitotic indices was
      detected at levels ?10MUM in the onions and reduction of root growth with
      ?100MUM. In the pollen fertility assays clear effects were observed at doses
      ?147.3mgkg(-1). Data concerning the annual use of the drug in European countries
      (France, Germany, Slovenia) enable the calculation of the predicted environmental
      concentration (PEC) values which are in the range between 3.3 and 5.0ngL(-1).
      Although comparisons with the genotoxic potencies of other commonly used
      cytostatic drugs and with highly active heavy metal compounds show that IM is an
      extremely potent genotoxin in higher plants, it is evident that the environmental
      concentrations are ?5 orders of magnitude lower as the levels which are required
      to cause adverse effects. 

PMID- 24560281
TI  - Bioaccumulation characterization of cadmium by growing Bacillus cereus RC-1 and
      its mechanism.
AB  - In an effort to explore the protective mechanism of growing Bacillus cereus RC-1
      against the toxicity of different Cd(II) concentrations, bacterial growth,
      cadmium consumption, surface interactions and intra- and extra-cellular Cd(II)
      contents were examined. Cellular morphology and growth were evidently affected by
      the initial metal concentrations above 20 mg L(-1), according to the analysis of
      SEM, AFM, TEM and UV spectrophotometer. Surface complexation and electrostatic
      attraction played an important role in the different Cd(II) concentrations, as
      determined by the FTIR and Zeta potential analysis. Intracellular accumulation
      was the predominant mechanism in culture with lower metal concentrations (below
      20 mg L(-1)), but was overshadowed by extracellular adsorption at higher
      concentrations. This suggested that the growing cells might employ one dominant
      mechanism at lower concentrations and then shift to another at higher
      concentrations. These results suggest options could be exploited for
      bioremediation of aqueous solution in which the Cd(II) concentration is less than
      20 mg L(-1).

PMID- 24560282
TI  - Leaching of brominated flame retardants from mixed wastes in lysimeters under
      conditions simulating landfills in developing countries.
AB  - In developing countries, wastes are usually not separated before being disposed
      of in solid-waste landfills, most of which are open dumps without adequate
      measures to prevent environmental pollution. To understand the leaching behavior
      of brominated flame retardants (BFRs) from waste consumer products in landfills,
      we have been conducting a long-term landfill lysimeter experiment since 2006
      under conditions designed to mimic three types of landfill conditions in
      developing countries: aerobic, semi-aerobic, and anaerobic. Pilot-scale
      lysimeters (60-cm i.d.) were filled with a 400-cm layer of mixed wastes
      consisting of 35 wt% food, 20 wt% paper, 20 wt% paper pulp, 13 wt% plastic, 10
      wt% wood chips, 1 wt% glass, and 1 wt% metals, proportions that are typical of
      unsorted municipal solid waste in Asian developing countries. In the present
      study, we determined the concentrations of polybrominated diphenyl ethers,
      tetrabromobisphenol A, tribromophenols, and hexabromocyclododecanes in leachate
      samples collected from the lysimeters during the first 3.5 years of the
      experiment, to evaluate BFR elution behavior in early-stage landfills. Under all
      three conditions, BFR elution started at the beginning of the experiment. The BFR
      concentrations in the leachates from the aerobic lysimeter tended to be lower
      than those from the anaerobic lysimeter, suggesting that the presence of air
      inside landfills considerably reduces BFR elution to the surrounding environment.
      During the 3.5-year experiment, BFR outflow from the lysimeters was only 0.001
      0.58% of the total BFRs in the loaded waste; that is, most of the BFRs in the
      waste remained in the lysimeters.

PMID- 24560283
TI  - Role of phosphate fertilizers in heavy metal uptake and detoxification of toxic
      metals.
AB  - As a nonrenewable resource, phosphorus (P) is the second most important
      macronutrient for plant growth and nutrition. Demand of phosphorus application in
      the agricultural production is increasing fast throughout the globe. The
      bioavailability of phosphorus is distinctively low due to its slow diffusion and
      high fixation in soils which make phosphorus a key limiting factor for crop
      production. Applications of phosphorus-based fertilizers improve the soil
      fertility and agriculture yield but at the same time concerns over a number of
      factors that lead to environmental damage need to be addressed properly.
      Phosphate rock mining leads to reallocation and exposure of several heavy metals
      and radionuclides in crop fields and water bodies throughout the world. Proper
      management of phosphorus along with its fertilizers is required that may help the
      maximum utilization by plants and minimum run-off and wastage. Phosphorus
      solubilizing bacteria along with the root rhizosphere of plant integrated with
      root morphological and physiological adaptive strategies need to be explored
      further for utilization of this extremely valuable nonrenewable resource
      judiciously. The main objective of this review is to assess the role of
      phosphorus in fertilizers, their uptake along with other elements and signaling
      during P starvation. 

PMID- 24560284
TI  - Multi-technique quantitative analysis and socioeconomic considerations of lead,
      cadmium, and arsenic in children's toys and toy jewelry.
AB  - A wide spectrum and large number of children's toys and toy jewelry items were
      purchased from both bargain and retail vendors and analyzed for arsenic, cadmium,
      and lead metal content using multiple analytical techniques, including flame and
      furnace atomic absorption spectroscopy as well as X-ray fluorescence
      spectroscopy. Particularly dangerous for young children, metal concentrations in
      toys/toy jewelry were assessed for compliance with current Consumer Safety
      Product Commission (CPSC) regulations (F963-11). A conservative metric involving
      multiple analytical techniques was used to categorize compliance: one technique
      confirmation of metal in excess of CPSC limits indicated a "suspect" item while
      confirmation on two different techniques warranted a non-compliant designation.
      Sample matrix-based standard addition provided additional confirmation of non
      compliant and suspect products. Results suggest that origin of purchase, rather
      than cost, is a significant factor in the risk assessment of these materials with
      57% of toys/toy jewelry items from bargain stores non-compliant or suspect
      compared to only 15% from retail outlets and 13% if only low cost items from the
      retail stores are compared. While jewelry was found to be the most problematic
      product (73% of non-compliant/suspect samples), lead (45%) and arsenic (76%) were
      the most dominant toxins found in non-compliant/suspect samples. Using the
      greater Richmond area as a model, the discrepancy between bargain and retail
      children's products, along with growing numbers of bargain stores in low-income
      and urban areas, exemplifies an emerging socioeconomic public health issue. 

PMID- 24560285
TI  - A review on catalytic applications of Au/TiO2 nanoparticles in the removal of
      water pollutant.
AB  - Nanomaterials are showing great potential for the improvement of water treatment
      technologies. In recent years, catalysis and photocatalysis processes using gold
      nanoparticles (Au-NPs) have received great attention due to their effectiveness
      in degrading and mineralizing organic compounds. This paper aims to review and
      summarize the recently published works and R & D progress in the field of
      photocatalytic oxidation of various water pollutants such as toxic organic
      compounds (i.e. azo dyes and phenols) by Au-NPs/TiO2 under solar, visible and UV
      irradiation. Extensive research which has focused on the enhancement of
      photocatalysis by modification of TiO2 employing Au-NPs is also reviewed.
      Moreover, the effects of various operating parameters on the photocatalytic
      activity of these catalysts, such as size and loading amount of Au-NPs, pH and
      calcination, are discussed. The support type, loading amount and particle size of
      deposited Au-NPs are the most important parameters for Au/TiO2 catalytic
      activity. Our study showed in particular that the modification of TiO2, including
      semiconductor coupling, can increase the photoactivity of Au/TiO2. In contrast,
      doping large gold NPs can mask or block the TiO2 active sites, reducing
      photocatalytic activity. The optimized loading amount of Au-NP varied for each
      experimental condition. Finally, research trends and prospects for the future are
      briefly discussed. 

PMID- 24560286
TI  - Copulation order, density cues and variance in fertilization success in a
      cestode.
AB  - Simultaneous hermaphrodites maximize their fitness by optimizing their investment
      into male or female functions. Allocation of resources to male function (tissues,
      traits, and/or behaviours increasing paternity) is predicted to increase as
      density, and the associated level of sperm competition, increases. We tested
      whether the simultaneous hermaphroditic cestode Schistocephalus solidus uses cues
      of potential partner densities in its fish intermediate host to improve its male
      reproductive success in the final host. We had two worms, one originating from a
      multiple infection in the fish intermediate host and one from a single infection,
      sequentially compete to fertilize the eggs of a third worm. The fertilization
      rates of the two competitors nearly always differed from the 50-50 null
      expectation, sometimes considerably, implying there was a 'winner' in each
      experimental competition. However, we did not find a significant effect of
      density in the fish host (single vs multiple) or mating order on paternity.
      Additional work will be needed to identify the traits and environmental
      conditions that explain the high variance in male reproductive success observed
      in this experiment.

PMID- 24560288
TI  - [How to define refractory overactive bladder?].

PMID- 24560287
TI  - A comparison of two methods for estimating DCE-MRI parameters via individual and
      cohort based AIFs in prostate cancer: a step towards practical implementation.
AB  - Multi-parametric Magnetic Resonance Imaging, and specifically Dynamic Contrast
      Enhanced (DCE) MRI, play increasingly important roles in detection and staging of
      prostate cancer (PCa). One of the actively investigated approaches to DCE MRI
      analysis involves pharmacokinetic (PK) modeling to extract quantitative
      parameters that may be related to microvascular properties of the tissue. It is
      well-known that the prescribed arterial blood plasma concentration (or Arterial
      Input Function, AIF) input can have significant effects on the parameters
      estimated by PK modeling. The purpose of our study was to investigate such
      effects in DCE MRI data acquired in a typical clinical PCa setting. First, we
      investigated how the choice of a semi-automated or fully automated image-based
      individualized AIF (iAIF) estimation method affects the PK parameter values; and
      second, we examined the use of method-specific averaged AIF (cohort-based, or
      cAIF) as a means to attenuate the differences between the two AIF estimation
      methods. Two methods for automated image-based estimation of individualized
      (patient-specific) AIFs, one of which was previously validated for brain and the
      other for breast MRI, were compared. cAIFs were constructed by averaging the iAIF
      curves over the individual patients for each of the two methods. Pharmacokinetic
      analysis using the Generalized kinetic model and each of the four AIF choices
      (iAIF and cAIF for each of the two image-based AIF estimation approaches) was
      applied to derive the volume transfer rate (K(trans)) and extravascular
      extracellular volume fraction (ve) in the areas of prostate tumor. Differences
      between the parameters obtained using iAIF and cAIF for a given method (intra
      method comparison) as well as inter-method differences were quantified. The study
      utilized DCE MRI data collected in 17 patients with histologically confirmed PCa.
      Comparison at the level of the tumor region of interest (ROI) showed that the two
      automated methods resulted in significantly different (p<0.05) mean estimates of
      ve, but not of K(trans). Comparing cAIF, different estimates for both ve, and
      K(trans) were obtained. Intra-method comparison between the iAIF- and cAIF-driven
      analyses showed the lack of effect on ve, while K(trans) values were
      significantly different for one of the methods. Our results indicate that the
      choice of the algorithm used for automated image-based AIF determination can lead
      to significant differences in the values of the estimated PK parameters. K(trans)
      estimates are more sensitive to the choice between cAIF/iAIF as compared to ve,
      leading to potentially significant differences depending on the AIF method. These
      observations may have practical consequences in evaluating the PK analysis
      results obtained in a multi-site setting. 

PMID- 24560289
TI  - [Guidelines concerning urinary incontinence in elderly: construction and
      validation of GRAPPPA algorithm].
AB  - OBJECTIVES: Provide guidelines presented as an algorithm for practical evaluation
      and first line therapy of urinary incontinence in elderly. PATIENTS AND METHODS:
      Guidelines using formalized consensus guidelines method. These guidelines have
      been validated by a group of 40 experts quoting proposals, subsequently reviewed
      by an independent group of multidisciplinary experts (urologist, general
      practitioner, neurologist, gynecologist, geriatrist, specialist in physical
      medicine and rehabilitation). RESULTS: By means of 3 rounds of interrogation of
      the expert panel, GRAPPPA algorithm was constructed. This algorithm take in
      account both evaluation and first line therapeutic options in the different type
      of incontinences observed in this population (urge, stress and mixed
      incontinence). Initial evaluation consists to track down urinary retention (and
      subsequently fecal stool impaction, use of anticholinergic or morphinic drugs),
      urinary tract infection and cognitive impairment. Haematuria, bladder-pelvic
      pain, history of radiotherapy or recent pelvic surgery, lead to refer the patient
      to a specialized unit. First line therapy is in all the cases pelvic floor
      training, use of local oestrogenotherapy and dietetic measures. In urge
      incontinence, anticholinergic drugs may be used. CONCLUSIONS: Implementation of
      this algorithm may promote best practice in management of urinary incontinence in
      elderly.

PMID- 24560290
TI  - [Pelvic floor muscles training, electrical stimulation, bladder training and
      lifestyle interventions to manage lower urinary tract dysfunction in multiple
      sclerosis: a systematic review].
AB  - AIM: To assess the effectiveness of conservative therapeutic approaches in a
      multiple sclerosis population. MATERIAL: Review was performed in PubMed, PEDro,
      Scopus and Cochrane Library using combinations of the following keywords:
      multiple sclerosis; bladder dysfunction; overactive bladder; detrusor
      hyperreflexia; urge incontinence; urgency; stress incontinence; pelvic floor
      muscle; biofeedback; PTNS; tibial nerve; bladder training; physical therapy;
      physiotherapy; conservative treatment and behavioral therapy. RESULTS: Six
      randomized articles including 289 patients were selected. Four papers exhibited
      strong scores for the methodological quality assessment. The parameters always
      significantly improved concerned: number of incontinence episodes (decreased from
      64% to 86% after treatment versus before treatment), quality of life (P<=0.001),
      severity of irritative symptoms (decreased by more than 50% after treatment
      versus before treatment), and nocturia (P=0.035 to P<0.001). Activities and
      participation, maximum flow rate, mean voided volume and daytime frequency were
      not significantly improved in all trials. CONCLUSIONS: The physical therapy
      techniques could be effective for the treatment of urinary disorders in multiple
      sclerosis populations with mild disability. However, the analyses are based on
      six studies within only four showed good methodological quality. No strong
      conclusions regarding treatment approaches can be drawn from this review.

PMID- 24560291
TI  - [Sensitivity to change of the USP score (Urinary Symptoms Profile) after surgical
      treatment of benign prostatic hyperplasia (BPH)].
AB  - OBJECTIVE: To evaluate the sensitivity to change in USP score (Urinary Symptoms
      Profile) after surgical treatment of benign prostatic hyperplasia (BPH). PATIENTS
      AND METHODS: Prospective study collecting IPSS (International Prostatic Symptom
      Score) and USP scores before and 6 weeks after surgery for BPH. Sensitivity to
      change was assessed using effect size (ES) and mean standardized response (MSR).
      RESULTS: Thirty patients, mean age of 68+/-10 years (min: 52, max: 90) were
      included in this study. The mean IPSS and USP scores were 14.3 (e.t.: 5.42), 20.3
      (e.t.: 5.22) and 3.53 (e.t.: 3.68), 3.43 (e.t.: 3.48) before and after surgery
      respectively. The overall USP score showed excellent sensitivity to change with a
      global value of ES and MSR of 1.986 and 2.322 respectively. CONCLUSION: The USP
      score has an excellent sensitivity to change. It seems to be a valid and reliable
      score that can be perfectly adapted to the assessment of symptoms associated with
      BPH, with good sensitivity to changes in the overall score, with the advantage
      over the IPSS of an exhaustive exploration of all urinary symptoms particularly
      in the field of urge urinary incontinence and stress urinary incontinence. LEVEL
      OF PROOF: 4.

PMID- 24560292
TI  - [Botulinum A toxin and detrusor sphincter dyssynergia: retrospective study of 47
      patients].
AB  - INTRODUCTION: To assess the efficacy of injections of botulinum toxin type A (BT
      A) in the urethral sphincter for treating detrusor sphincter dyssynergia (DSD).
      PATIENTS AND METHODS: Retrospective observational study of patients with
      confirmed urodynamic DSD (neurological and non-neurological etiologies) treated
      at our center from 2002 to 2010. All patients received 300 IU of DYSPORT(r)
      injected transperineally under electromyographic control. Using a visual analog
      scale (VAS) for mictional disorders and the measure of the post-void residual
      (PVR) as criteria of efficacy, results were classified as "non-satisfactory"
      (decrease in the VAS<2 or decrease in the PVR<20%), "intermediate" (decrease in
      the VAS>=2 or decrease in the PVR>=20%) or "satisfactory" (decrease in the VAS>3
      or decrease in the PVR>40%). RESULTS: Records of 47 patients (7 women and 40 men)
      were studied. Mean follow-up was 14.2 months. At the end of follow-up, there were
      23.4% (11) of "satisfactory" results, 19.1% (9) of "intermediate" results, 42.6%
      (20) of "non-satisfactory" results and 14.9% (7) of patients lost for follow-up.
      The mean decrease in PVR was 60 mL (from an average of 212 to an average of 152
      mL). No side effect was observed. CONCLUSION: In this small series reporting the
      results of the injection of BT-A in the urethral sphincter for DSD, we observed
      42.5% of satisfactory or intermediate results without associated side effects.

PMID- 24560293
TI  - [Impact of a training workshop on residents and senior registrar skill in
      diagnosis and repair of anal sphincter and rectal mucosae obstetrical injuries].
AB  - OBJECTIVE: To evaluate the impact of a training workshop on residents and senior
      registrar skill in repair of anal sphincter and rectal mucosae obstetrical
      injury. MATERIAL AND METHODS: Residents and senior registrar practical and
      theoretical knowledge were evaluated by a questionnaire sent, using AGOF
      (association des gynecologues-obstetriciens en formation) mailing list. This
      questionnaire includes questions about epidemiology, risk factors and sutures
      types. Scores were compared according to the participation or not at the
      workshop. RESULTS: There were 106 residents or senior registrar (48.4%) in the
      workshop group and 113 (51.6%) in the control group. Scores were significantly
      higher in the workshop group than in the control group for theoretical knowledge
      (4.1 vs. 3.7), practical knowledge (17.6 vs. 15.9) and global scores (21.7 vs.
      19.7). There was no difference according to the participation before or after the
      third residency semester. Residents global scores were statistically higher in
      the workshop group compared to the control group (21.8 vs. 19.5) but there was no
      significant difference between the senior registrar of the two group.
      Participants in the workshop group estimate themselves significantly more
      efficient than in the control group concerning anal sphincter injury repair and
      rectal mucosae repair. CONCLUSION: A training workshop seems to improve the
      theoretical and practical skill. LEVEL OF EVIDENCE: 4.

PMID- 24560294
TI  - [Consequences of coelioscopic sacrocolopoxy on the sexuality of the couple].
AB  - AIM: To assess the impact on the sexuality of the couple of pelvic organ prolapse
      repair with coelioscopic sacrocolopoxy. MATERIAL: Pilot, prospective, monocentre
      study conducted in Nimes university hospital. Consecutive patients undergoing
      coelioscopic sacrocolpopexy and their partner were invited to participate. Women
      attended a pre-surgical visit and a 6-month post-surgery visit where pelvic organ
      prolapse status was clinically assessed. In the same time, they and their partner
      filled general quality of life and specific sexual quality of life questionnaires
      (questionnaires PISQ12, PFDI-20 in women, medical history, IIEF, modified PISQ12
      questionnaires in men). RESULTS: From May to December 2010, 25 couples were
      assessed. Anatomical success rates (POPQ<2) in the middle, anterior and posterior
      compartments were respectively of 100%, 95.4% and 66.7%. After surgery, 65.2% of
      pairs (n=15) reported an at least hebdomadal frequency of sexual intercourse, as
      compared with 54.2% (n=13) of pairs before surgery (P<0.001). Two cases of
      decrease of sexual intercourses frequency were reported and appeared partner
      related. There was an overall non-significant improvement in sexual quality of
      life in men and women. General pelvic organ distress, urinary incontinence and
      specific pelvic organ prolapse distresses were significantly improved after
      surgery. CONCLUSION: Coelioscopic sacrocolpopexy does not impair couple's
      sexuality, assessed as sexual intercourses frequency and could even improve it.
      Partner's assessment can bring important information with respect to the
      interpretation of functional sexual results of surgery.

PMID- 24560295
TI  - Regulatory Peptides--past, present and future.

PMID- 24560297
TI  - Evaluating stent optimisation technique (StentBoost(r)) in a dedicated
      bifurcation stent (the TrytonTM).
AB  - BACKGROUND/PURPOSE: To evaluate the use of StentBoost(r) in the TrytonTM
      dedicated SideBranch Stent. METHODS & RESULTS: The TrytonTM SideBranch Stent has
      been effectively used to manage complex bifurcations. However, the paucity of
      scaffolding in the proximal part of the stent makes it often difficult to
      visualise under standard radiographic imaging. We set out to evaluate whether by
      using an augmented radiographic imaging technique it was possible to aid
      visualisation of the stent. In particular the so call 'wedding ring' band which
      is crucial to the procedural success. We further evaluated whether it was
      possible to determine the apposition of the stent at the carina, its coverage and
      the ability to aid recrossing of the struts closest to the carina as well as the
      added radiation exposure. CONCLUSIONS: StentBoost(r) was found to be invaluable
      to the procedural success of the TrytonTM deployment without adding any extra
      cost to the procedure and with only a 3.7% increase in radiation to the patient.
      It allowed enhanced visualisation in all cases to aid apposition, recrossing and
      coverage.

PMID- 24560298
TI  - Efficacy of mother-child-grandchild technique: 4F and 5F inner catheters through
      mother guide catheter.
AB  - Stent delivery failure to the distal lesion was still encountered even after the
      introduction of mother-child technique using a 5F or 4F child catheter. A 5F
      inner catheter with a length of 112cm, and a 4F inner catheter with a length of
      122cm enabled a novel mother-child-grandchild technique. In in vitro experiments,
      not only was backup support increased, but superior trackability could also be
      obtained with the mother-child-grandchild technique, over the mother-child
      technique. We describe the clinical data using this novel mother-child-grandchild
      technique to deliver a stent to the severely bended and/or calcified distal
      lesion.

PMID- 24560296
TI  - Insights into the glycosylase search for damage from single-molecule fluorescence
      microscopy.
AB  - The first step of base excision repair utilizes glycosylase enzymes to find
      damage within a genome. A persistent question in the field of DNA repair is how
      glycosylases interact with DNA to specifically find and excise target damaged
      bases with high efficiency and specificity. Ensemble studies have indicated that
      glycosylase enzymes rely upon both sliding and distributive modes of search, but
      ensemble methods are limited in their ability to directly observe these modes.
      Here we review insights into glycosylase scanning behavior gathered through
      single-molecule fluorescence studies of enzyme interactions with DNA and provide
      a context for these results in relation to ensemble experiments. 

PMID- 24560300
TI  - Pathophysiology of takotsubo syndrome: acute cardiac sympathetic disruption
      (ACSD) syndrome.

PMID- 24560299
TI  - Management of distal/bifurcation left main restenosis after drug eluting stents
      implantation: single center experience.
AB  - OBJECTIVES: Restenosis after drug eluting stent (DES) implantation in the
      distal/bifurcation left main (DBLM) remains challenging to manage. The aim of
      this study was to assess the in-stent restenosis (ISR) after DES implantation in
      DLM and to evaluate current management strategy. METHODS: The medical records of
      patients referred for LM distal/bifurcation percutaneous coronary interventions
      (PCI) from the same Cardiology Unit in the January 2007 to December 2012 period
      were reviewed for PCI technique, stent type, restenosis type, restenosis
      treatment and management (CABG, balloon angioplasty only, alternative DES
      implant, drug eluting balloon angioplasty). RESULTS: Fourteen patients (5
      females, mean age 75.1+/-8.3years) out of 89 (15.7%) having undergone a
      percutaneous coronary interventions on DBLM with DES, developed restenosis
      (everolimus stents in 10 patients, zotarolimus stents in 4 patients). Technique
      used at the first implant included stenting of the main branch in 4 patients,
      culottes stenting in 6 patients and T-stent in 4 patients. The mean time elapsed
      from the first angioplasty and ISR intervention was 7.6+/-3.6months. Restenosis
      treatments included: implantation of a different DES (in 3 patients),
      implantation of a bare-metal stent (in 2 patients), simple balloon angioplasty
      (in 4 patients), and drug-eluting balloon (5 patients). At 6-month angiographic
      control second restenosis rate was 14.2%. After a mean follow-up of 38.5+/
      24.4months the target vessel revascularization was 14.3%: surgery was the final
      choice in two patients due to recurrent restenosis. Incidence of major adverse
      cardiac event was 28.5%. CONCLUSIONS: The occurrence of restenosis after DBLM
      following DES implantation is not frequent but remains difficult to manage. In
      our small anecdotal series, all the different strategies including implantation
      of different DES, balloon angioplasty, bare-metal stent implantation and drug
      eluting balloon angioplasty appeared equally effective in maintaining arterial
      patency.

PMID- 24560301
TI  - FibromiRs: translating molecular discoveries into new anti-fibrotic drugs.
AB  - Fibrosis, or tissue scarring, is defined as excessive and persistent accumulation
      of extracellular matrix components in response to chronic tissue injury. Fibrosis
      is a pathological feature characterizing nearly all forms of chronic organ
      failure. Fibroproliferative disorders of liver, kidney, heart, and lung are
      frequently associated with considerable morbidity and mortality worldwide.
      Limited therapeutic options are available; none is yet effective in stopping the
      ultimate progression of the disease. This has prompted investigations for new
      molecular targets. Recent studies have shown aberrant expression of miRNAs
      (fibromiRs) during the development of fibrosis. The challenge now is to
      understand how these aberrantly expressed miRNAs collaborate to drive
      fibrogenesis. Progress in understanding how fibromiRs contribute to tissue
      fibrosis is necessary to translate molecular discoveries into new therapeutics
      for fibroproliferative diseases. 

PMID- 24560302
TI  - Benefit from synchronous portal-superior mesenteric vein resection during
      pancreaticoduodenectomy for cancer: a meta-analysis.
AB  - BACKGROUND: Pancreaticoduodenectomy combined with portal-superior mesenteric vein
      synchronous resection for cancer remains a hot debate topic. The present study
      used meta-analytical technique to provide update information and an evidence
      based evaluation on both the perioperative benefit and long-term survival.
      METHODS: A meta-analysis was performed to evaluate studies comparing venous
      resection (VR) versus without venous resection (WVR) groups. 22 retrospective
      studies including 2890 patients were eligible for an analysis of perioperative
      morbidity, mortality, and long-term survival. Furthermore, subgroup analysis was
      made according to histopathology and resection margin status respectively for the
      purpose of survival assessment. RESULTS: There was no difference in perioperative
      morbidity, mortality and 1-year, 3-year survival between two groups, but showed
      differences in median tumor size (P < 0.001), R0 resection rate (P < 0.001),
      lymph node metastasis (P = 0.03), pancreatic fistula (P = 0.01), and 5-year
      survival (P = 0.03). In subgroup analysis, patients in venous resection group
      received R0 resection had a significantly better survival comparing with who
      received R1 resection both at 2-year (P < 0.001) and 5-year (P = 0.00002). In
      histopathology subgroup, patients in venous resection groups who had true tumor
      infiltration had a significantly bad survival comparing with whom only with
      inflammation pathology. CONCLUSION: Pancreaticoduodenectomy combined with venous
      resection can achieve equal perioperative morbidity and mortality as standard
      resection. However, in order to obtain an optimal survival outcome, surgeons
      should make an R0 resection as far as possible, especially in cases need
      synchronous venous resection.

PMID- 24560303
TI  - Adult colonoscopy or single-balloon enteroscopy-assisted ERCP in long-limb
      surgical bypass patients.
AB  - OBJECTIVE: The aim of this study was to evaluate the usefulness of adult
      colonoscopy or single-balloon enteroscopy (SBE)-assisted endoscopic retrograde
      cholangiopancreatography (ERCP) in long-limb surgical bypass patients. METHODS:
      Retrospective analysis of 16 patients with long-limb surgical bypasses who
      underwent therapeutic ERCP because of suspected pancreaticobiliary diseases.
      Small-bowel intubation was performed by peroral adult colonoscopy or SBE. If
      colonoscopy success was achieved, ERCP was performed subsequently. But in
      patients using SBE, a small-caliber colonoscope would be used to replace
      enteroscope if the SBE success was achieved. ERCP was then performed with the
      conventional accessories. RESULTS: A total of 21 ERCP procedures were performed.
      Adult colonoscope was used for ERCP in 8 patients with standard Whipple resection
      consecutively. Colonoscopy success was achieved in 8 of 8 patients (100%), of
      whom 7 of 8 (87.5%) achieved ERCP success. SBE-assisted ERCP was attempted in
      other 8 patients with different types of Roux-en-Y anatomy. SBE success was
      achieved in 7 of 8 patients (87.5%), of whom 4 of 7 (57.1%) achieved ERCP
      success. The overall success rate of endoscopy and ERCP was 93.8% (15/16) and
      68.8% (11/16), respectively. CONCLUSIONS: Adult colonoscopy has high success rate
      for performing ERCP after Whipple resection and should be selected for such
      patient preferentially. By using the facilitated method for endoscopic
      interventions at pancreaticobiliary disease after Roux-en-Y reconstruction, SBE
      assisted ERCP can be attempted when it is difficult to gain access to the papilla
      of Vater or bilioenteric/pancreaticoenteric anastomosis and long length ERCP
      accessories cannot be available.

PMID- 24560304
TI  - Intrahepatic cholestasis of pregnancy and hepatitis C virus: a criminal
      conspiracy?

PMID- 24560305
TI  - Duplex surveillance after endovascular revascularisation for critical limb
      ischaemia.
AB  - OBJECTIVE: Despite the popularity of endovascular therapy (EVT) for critical limb
      ischaemia (CLI), there are few studies investigating the efficacy of duplex
      ultrasound (DUS) surveillance after endovascular interventions. The aim of this
      study was to evaluate DUS surveillance after EVT for CLI. METHODS: 146
      endovascular procedures in 134 consecutive patients with CLI between 2011 and
      2012 were included. Follow-up visits with ankle-brachial index (ABI), toe
      pressure, and target vessel DUS were performed at 1, 3, and 6 months after
      revascularisation. RESULTS: The median age of the study population was 79 years,
      58% were males, and 55% had diabetes. The target artery was at the iliac, femoro
      popliteal, and infrapopliteal level in 2%, 54%, and 44% of cases, respectively.
      There were 282 follow-up visits. In 15 (5.3%) DUS examinations, the target vessel
      was not seen properly. In the remaining 267 DUS, the majority of the target
      arteries were patent with no or mild restenosis (n = 169, 63.3%), but in 98
      (36.7%) examinations, the target artery was stenosed or occluded. When DUS was
      compared with the clinical presentation, there was no correlation in 30% and when
      DUS and toe pressure were compared, discrepancy was seen in 29%. A re-angiogram
      was performed for 29 patients, and the DUS finding was verified in each case.
      During the mean follow-up of 11 months, a new endovascular intervention was
      performed on 37 (25.3%) limbs, and 4 (2.7%) underwent surgical bypass. Four
      (3.0%) patients died and 6 (4.5%) underwent major amputation. CONCLUSION:
      Clinical status or toe pressure alone were adequate markers of endovascular
      revascularisation failure in the majority of the patients, but would have missed
      up to one-third of the clinically significant re-stenoses or occlusions. DUS is
      therefore a valuable aid in surveillance after EVT for CLI, especially for
      patients with an ischaemic tissue lesion.

PMID- 24560306
TI  - Diagnosing dysglycemia in adolescents with polycystic ovary syndrome.
AB  - PURPOSE: Screening for impaired glucose tolerance (IGT) is recommended for
      adolescents with polycystic ovary syndrome (PCOS) with oral glucose tolerance
      test (OGTT). Whether glycated hemoglobin (HbA1c) can be used for screening in
      this patient population is unknown. We sought to determine the utility of HbA1c
      and 2-hour OGTT for diagnosing dysglycemia in adolescents with PCOS. METHODS:
      This was a retrospective cohort study of 68 adolescents with PCOS seen in the
      Boston Children's Hospital Division of Adolescent Medicine between 2008 and 2011
      and not known to have diabetes. Prevalence of dysglycemia (impaired fasting
      glucose, IGT, increased risk for diabetes, or diabetes mellitus as diagnosed by
      fasting plasma glucose, 2-hour OGTT, and/or HbA1c) and sensitivity and
      specificity of HbA1c for diagnosing dysglycemia compared with OGTT were assessed.
      RESULTS: Twenty-four participants had abnormal glucose testing, including one
      participant (1.5%) who met criteria for diabetes mellitus and 23 participants
      (34%) who met criteria for impaired fasting glucose/IGT/prediabetes. More
      patients were identified as having dysglycemia by HbA1c than OGTT. Compared with
      OGTT, HbA1c had a sensitivity of 60% and a specificity of 69% for diagnosing
      dysglycemia. CONCLUSIONS: In adolescents with PCOS, HbA1c had moderate
      sensitivity and specificity for detecting dysglycemia compared with OGTT.
      Clinicians should be aware that both tests have benefits and limitations, and the
      optimal test for follow-up requires further study.

PMID- 24560307
TI  - Assessing Iranian adolescent girls' needs for sexual and reproductive health
      information.
AB  - PURPOSE: To explore the views and experiences of adolescent girls and key adults
      regarding the necessity of providing sexual and reproductive health (SRH)
      information and services for adolescent girls in Iran. METHODS: This was a
      qualitative study; the data were coded and categorized in content analysis by
      MAXQDA10 and were gathered through focus groups with adolescent girls and their
      mothers and semi-structured interviews with school counselors, sociologists,
      health providers, state and nongovernmental directors of health programs, clergy,
      and health policy makers in the Iranian cities of Mashhad, Tehran, Shahroud, and
      Qom. RESULTS: There were six main reasons for the need to provide SRH services
      for adolescent girls: a lack of adequate knowledge about SRH, easy access to
      inaccurate information sources, cultural and social changes, increasing risky
      sexual behaviors among adolescents, religion's emphasis on sex training of
      children and adolescents, and the existence of cultural taboos. CONCLUSIONS: Most
      participants confirmed the necessity of providing SRH services for adolescent
      girls, so instead of talking about provision or non-provision of these services,
      it is important for policy makers to plan and provide SRH services that can be
      consistent with cultural and religious values for adolescent girls.

PMID- 24560315
TI  - Let's start at the very beginning: addressing the goal of service to the
      community.

PMID- 24560316
TI  - 50 Years ago in the Journal of Pediatrics: periodic breathing of premature
      infants.

PMID- 24560317
TI  - 50 Years ago in The Journal of Pediatrics: the hypotonic infant.

PMID- 24560318
TI  - 50 Years ago in The Journal of Pediatrics: hypoproteinemia and edema in infants
      with cystic fibrosis of the pancreas.

PMID- 24560319
TI  - Bracing reduces progression of high-risk curves in idiopathic scoliosis.

PMID- 24560320
TI  - One-fifth of high-school seniors participate in binge drinking.

PMID- 24560321
TI  - Delay in measles vaccination is associated with increased risk of post
      vaccination seizures.

PMID- 24560322
TI  - Adolescents with ADHD demonstrate driving inconsistency.

PMID- 24560323
TI  - Abdominal ultrasound is specific but insufficiently sensitive in diagnosing
      appendicitis.

PMID- 24560326
TI  - The endless story of digitalis.

PMID- 24560324
TI  - Patterns and predictors of intensive statin therapy among patients with diabetes
      mellitus after acute myocardial infarction.
AB  - Intensive statin therapy is a central component of secondary prevention after
      acute myocardial infarction (AMI), particularly among high-risk patients, such as
      those with diabetes mellitus (DM). However, the frequency and predictors of
      intensive statin therapy use after AMI among patients with DM have not been
      described. We examined patterns of intensive statin therapy use (defined as a
      statin with expected low-density lipoprotein cholesterol lowering of >50%) at
      discharge among patients with AMI with known DM enrolled in a 24-site US
      registry. Predictors of intensive statin therapy use were evaluated using
      multivariable hierarchical Poisson regression models. Among 1,300 patients with
      DM after AMI, 22% were prescribed intensive statin therapy at hospital discharge.
      In multivariable models, ST-elevation AMI (risk ratio [RR] 1.48, 95% confidence
      interval [CI] 1.29 to 1.70), insurance for medications (RR 1.28, 95% CI 1.00 to
      1.63), and higher low-density lipoprotein cholesterol levels (RR 1.05 per 1
      mg/dl, 95% CI 1.02 to 1.07) were independent predictors of intensive statin
      therapy, whereas higher Global Registry of Acute Coronary Events scores were
      associated with lower rates of intensive statin therapy (RR 0.94 per 10 points,
      95% CI 0.91 to 0.98). In conclusion, only 1 in 5 patients with DM was prescribed
      intensive statin therapy at discharge after an AMI. Predictors of intensive
      statin therapy use suggest important opportunities to improve quality of care in
      this patient population. 

PMID- 24560325
TI  - Which polyunsaturated fatty acids are active in children with attention-deficit
      hyperactivity disorder receiving PUFA supplementation? A fatty acid validated
      meta-regression analysis of randomized controlled trials.
AB  - Concerns about growth retardation and unknown effects on long-term brain
      development with stimulants have prompted interest in polyunsaturated fatty acid
      supplementation (PUFA) as an alternative treatment. However, randomized
      controlled trials (RCTs) and meta-analyses of PUFA supplementation in ADHD have
      shown marginal benefit, and uncertainty exists as to which, if any, PUFA might be
      effective in alleviating symptoms of ADHD. We conducted an updated meta-analysis
      of RCTs in ADHD together with multivariable meta-regression analyses using data
      on PUFA content obtained from independent fatty acid methyl ester analyses of
      each study PUFA regimen. The PubMed, Embase and PsycINFO databases were searched
      with no start date and up to 28th July 2013. Study inclusion criteria were:
      randomized design, placebo controlled, PUFA preparation as active intervention,
      reporting change scores on ADHD rating-scale measures. Rating-scale measures of
      inattention and hyperactive-impulsive symptoms were extracted, study authors were
      contacted to obtain missing data, studies not reporting negative findings had
      these data imputed, and study quality was assessed using the Jadad system plus
      other indicators. Random-effects models were used for pooled effects and for meta
      regression analyses. Standardized mean differences (SMD) in inattention,
      hyperactive-impulsive and combined symptoms were assessed as rated by parents,
      teachers or all raters. The influence of study characteristics and PUFA regimen
      content was explored in multivariable meta-regression analyses. The overall
      pooled estimate from 18 studies showed that combined ADHD symptoms rated by all
      raters decreased with PUFA supplementation; SMD -0.192 (95% CI: -0.297, -0.086;
      P<0.001). However, when analyzed by rater, only parent-rated symptoms decreased
      significantly. Multivariable meta-regression showed that longer study duration,
      gamma-linolenic acid (GLA), and the interaction between GLA and eicosapentaenoic
      acid (EPA) were associated with significant decreases in inattention; however,
      PUFA regimen content was unrelated to changes in hyperactive-impulsive symptoms.
      Certain fatty acids present in placebo preparations may potentially have been
      psychoactive. This meta-analysis provides modest evidence of PUFA effectiveness
      in ADHD, especially GLA and EPA for inattention symptoms; however, evidence of
      reporting bias, publication bias, variable methodological quality, and use of
      potentially psychoactive placebos limit the generalizability of these findings. 

PMID- 24560327
TI  - Observational studies cannot justify the inferior vena cava filter.

PMID- 24560328
TI  - The reply.

PMID- 24560329
TI  - Pocket ready to eat at home in primary care.

PMID- 24560331
TI  - The effect of radical treatment and rehabilitation on muscle mass and strength: a
      randomized trial in stages I-III lung cancer patients.
AB  - OBJECTIVES: Little is known about the impact of an oncological treatment on
      muscle mass and strength in patients with lung cancer and the impact of a
      subsequent rehabilitation program. This study investigates the effect of radical
      treatment and post-treatment pulmonary rehabilitation on muscle mass and strength
      in patients with lung cancer and the relationship between muscle mass and
      strength. METHODS: Lung cancer patients, candidate for radical treatment, were
      randomly (2:1) allocated after radical treatment to either standard follow up
      (CON) or a 12-week rehabilitation training program (RT). Muscle mass was
      estimated by bioelectric impedance and CT-scan. Muscle strength was estimated by
      measuring quadriceps force (QF) with a hand held dynamometer. All variables were
      measured before (M1) and after radical treatment (M2), and at the earliest 12
      weeks after randomization (M3). Data are presented as means with standard
      deviation. RESULTS: 45 lung cancer patients (age: 65 years (9)) participated in
      the study. At M2, both muscle cross sectional area (MCSA) and QF were
      significantly decreased (p<0.05). 28 patients were randomized. 13/18 RT and 9/10
      CON patients ended the trial. At M3, RT-patients improved significantly their
      MCSA compared to CON-patients (DeltaMCSA: 6 cm(2) (6) (p=0.003) vs. 1cm(2) (11)
      (p=0.8)). CONCLUSION: Muscle mass and strength: (1) are decreased at presentation
      in a substantial part of lung cancer patients; (2) are significantly negatively
      affected by radical treatment and (3) completely recover after a 12 week
      structured rehabilitation program, whereas a further decline was observed in CON
      patients.

PMID- 24560330
TI  - Phase 2 trial of neoadjuvant axitinib in patients with locally advanced
      nonmetastatic clear cell renal cell carcinoma.
AB  - BACKGROUND: Previous studies have shown a modest impact of tyrosine kinase
      inhibitors on primary renal tumors. Those studies were mostly retrospective or
      heterogeneous in their eligibility criteria with regard to histology, disease
      stage, duration of therapy, and time off therapy prior to surgery. OBJECTIVE: To
      prospectively investigate the safety and efficacy of axitinib in downsizing
      tumors in patients with nonmetastatic biopsy-proven clear cell renal cell
      carcinoma (ccRCC). DESIGN, SETTING, AND PARTICIPANTS: This was a single
      institution, single-arm phase 2 clinical trial. Patients with locally advanced
      nonmetastatic biopsy-proven ccRCC were eligible. INTERVENTION: Patients received
      axitinib 5mg for up to 12 wk. Axitinib was continued until 36h prior to surgery.
      Patients underwent partial or radical nephrectomy after axitinib therapy. OUTCOME
      MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was objective response
      rate prior to surgery. Secondary outcomes included safety, tolerability, and
      quality of life. A dedicated radiologist independently reviewed all computed
      tomography scans to evaluate for response using Response Evaluation Criteria in
      Solid Tumors (RECIST). RESULTS AND LIMITATIONS: A total of 24 patients were
      treated. Twenty-two patients continued axitinib for 12 wk; 1 patient continued
      axitinib for 11 wk and underwent surgery as planned. One patient stopped
      treatment at 7 wk due to adverse events (AEs). Median reduction of primary renal
      tumor diameter was 28.3%. Eleven patients experienced a partial response per
      RECIST; 13 had stable disease. There was no progression of disease while on
      axitinib. The most common AEs were hypertension, fatigue, oral mucositis,
      hypothyroidism, and hand-foot syndrome. Postoperatively, 2 grade 3 and 13 grade 2
      complications were noted. No grade 4 or 5 complications occurred. Functional
      Assessment of Cancer Therapy-Kidney Specific Index-15 changed over time, with
      quality of life worsening while on therapy, but by week 19, it was not
      statistically different from screening. Limitations include single-arm design and
      small patient numbers. CONCLUSIONS: Axitinib was clinically active and reasonably
      well tolerated in the neoadjuvant setting in patients with locally advanced
      nonmetastatic ccRCC. PATIENT SUMMARY: In this prospective clinical trial, we
      found that axitinib, when given prior to surgery, results in significant
      shrinking of kidney cancers. Larger studies are needed prior to further clinical
      use. TRIAL REGISTRATION: This clinical trial was registered with
      clinicaltrials.gov (NCT01263769).

PMID- 24560332
TI  - Open, randomized, multi-center phase II study comparing efficacy and tolerability
      of Erlotinib vs. Carboplatin/Vinorelbin in elderly patients (>70 years of age)
      with untreated non-small cell lung cancer.
AB  - BACKGROUND: Targeting the epidermal-growth-factor-receptor (EGFR) in non-small
      cell lung cancer (NSCLC) is an established treatment option with less toxicity
      compared to conventional chemotherapy. This study was undertaken to determine
      whether Erlotinib is non-inferior compared to chemotherapy as a first-line
      therapy in unselected elderly patients. MATERIALS AND METHODS: Patients >= 70
      years with untreated, metastatic NSCLC were randomized to Erlotinib (E), 150
      mg/day or Carboplatin (AUC5) plus Vinorelbine (25mg/m(2) on days 1 and 8) every
      three weeks (CV). Primary endpoint was progression-free survival (PFS). After
      progression, crossover was strongly recommended. Secondary endpoints were
      duration of response, 1-year survival, overall survival (OS), response rate (RR),
      quality of life (FACT-L), assessment of comorbidities by simplified comorbidity
      score (SCS) and Charlsons' comorbidity score, safety and assessment of molecular
      markers. RESULTS: Between June 2006 and August 2008 284 pts were randomized to E
      (144) and CV (140). PFS was significantly inferior with E (median PFS 2.4 versus
      4.6 months [HR 1.6, 75% CI 1.22-2.09, p: 0.0005]) as well as RR (7.8% v 28.3%, p:
      0.0001). No significant difference in OS appeared (median E: 7.3 months versus
      CV: 8.4 months, HR: 1.24 [75% CI 0.9-1.71]). In never smokers PFS (median PFS:
      3.7 v 4.3 m, E v CV, HR 0.72, 75% CI 0.35-1.48) and OS (median: 16.5 versus 17
      months, HR 0.99 [75% CI 0.38-2.57]) were comparable. More skin toxicity and
      diarrhea was seen with E compared to more myelotoxicity, neurotoxicity and
      constipation with CV. Less severe adverse events were observed with E (81 v 102,
      E v CV). CONCLUSION: CV had an increased efficacy compared with E in an
      unselected population of elderly patients with advanced NSCLC.

PMID- 24560333
TI  - Lung cancer incidence in Singapore: ethnic and gender differences.
AB  - OBJECTIVES: Lung cancer is the leading cause of cancer death in Singapore. We
      examine trends of lung cancer from 1968 to 2007, explore ethnic and gender
      specific incidence rates, and examine period and cohort effects in Chinese and
      Malays using Age-Period-Cohort (APC) analysis. METHODS: Aggregated data for
      cancer incidences and estimated person-years for the period 1968-2007 were
      obtained from the Singapore Cancer Registry. An APC analysis was performed using
      a Poisson regression model. RESULTS: Lung cancer incidence rates were more than
      two times higher in males compared to females, and also higher in Chinese
      compared to Malays and Indians. While rates in Chinese men, and, to a lesser
      extent, Chinese women, had been declining since the early 1980s, rates in Malay
      men continued to increase. The full APC model described the cancer trend in
      Chinese males, Chinese females and Malay males, while an age-drift model
      described the cancer trend in Malay females. Among Chinese males, Chinese females
      and Malay males, there was no clear pattern to the period curvature effects,
      although similar cohort curvatures were seen, with positive curvature effects in
      older cohorts that declined towards zero and negative effects in younger cohorts.
      CONCLUSION: There are strong gender and ethnic differences in lung cancer
      incidence in Singapore. Differences in smoking rates and differential ethnic
      effects of smoking may explain some but not all of these differences. The similar
      cohort curvatures suggest that environmental factors in Singapore occurring in
      the past but no longer present at similar intensity or frequency may explain the
      positive deviation from a linear trend. Apart from smoking, other environmental
      factors such as changes in diet, improved sanitation and ventilation, and
      declines in infectious diseases like tuberculosis may play a role.

PMID- 24560334
TI  - Clinically relevant determinants of body composition, function and nutritional
      status as mortality predictors in lung cancer patients.
AB  - Lung cancer belongs to the type of tumors with a relatively high frequency of
      malnutrition, sarcopenia and cachexia, severe metabolic syndromes related to
      impairment of physical function and quality of life, resistance to therapy and
      short survival. Inexpensive and accessible methods of evaluating changes in body
      composition, physical function and nutrition status are for this reason of great
      importance for clinical practice to enable the early identification, monitoring,
      preventing and treatment of these nutritional deficiencies. This could lead to
      improved outcomes in the quality of life, physical performance and survival of
      patients with lung cancer. The aim of this article is to summarize the recent
      knowledge for the use of such methods, their predictability for patient outcomes
      and an association with other clinically relevant parameters, specifically with
      lung cancer patients, because such an article collectively describing their
      practical application in clinical practice is lacking. The interest of this
      article is in the use of anthropometry, handgrip dynamometry, bioelectrical
      impedance analysis derived phase angle and nutritional screening questionnaires
      in lung cancer patients. 

PMID- 24560335
TI  - Adenocarcinoma arising in an extralobar sequestration: a case report and review
      of the literature.
AB  - Extralobar sequestration is a type of bronchopulmonary foregut malformation
      defined as an isolated portion of lung tissue with a systemic arterial supply,
      its own pleural investment, and no bronchial communication. While it may be
      recognized in utero or in the neonatal period, depending on its location and
      associated anomalies, it can also go unrecognized until later in life when it may
      present as a mass. We report the first case of adenocarcinoma arising in an
      extralobar sequestration. The patient was a 70-year old man with a 55 pack year
      smoking history who presented with chest discomfort and was found to have a 6.5
      cm right lower lobe mass. Percutaneous biopsy of the mass was positive for
      adenocarcinoma. At surgery, the mass was noted to have a separate arterial
      connection, no bronchial communication, and its own pleural investment,
      consistent with an extralobar sequestration. Malignancy arising in pulmonary
      sequestrations is rare and the few reported cases have been in intralobar types.
      Carcinoma arising in this setting adds to the dilemma of whether or not these
      developmental anomalies should be excised or followed. Our tumor, while small,
      did have vascular invasion.

PMID- 24560336
TI  - Effect of vitamin E and C supplementation on oxidative damage and total
      antioxidant capacity in lead-exposed workers.
AB  - The molecular response of the antioxidant system and the effects of antioxidant
      supplementation against oxidative insult in lead-exposed workers has not been
      sufficiently studied. In this work, antioxidants (vitamin E 400 IU+vitamin C
      1g/daily) were supplemented for one year to 15 workers exposed to lead (73 MUg of
      lead/dl of blood) and the results were compared with those on 19 non-lead exposed
      workers (6.7 MUg of lead/dl). Lead intoxication was accompanied by a high
      oxidative damage and an increment in the erythrocyte antioxidant response due to
      increased activity of catalase and superoxide dismutase. Antioxidant
      supplementations decreased significantly the oxidative damage as well as the
      total antioxidant capacity induced by lead intoxication with reduction of the
      antioxidant enzyme activities. We conclude that antioxidant supplementation is
      effective in reducing oxidative damage and induces modifications in the
      physiopathological status of the antioxidant response in lead-exposed workers.

PMID- 24560337
TI  - Biomarkers for monitoring transfluthrin exposure: urinary excretion kinetics of
      transfluthrin metabolites in rats.
AB  - The urinary excretion kinetics of a fluorine-containing pyrethroid transfluthrin
      [(2,3,5,6-tetrafluorophenyl)methyl 3-(2,2-dichloroethenyl)-2,2
      dimethylcyclopropane-1-carboxylate], which is widely used recently as mosquito
      repellents, was examined in rats to search for urinary metabolites suitable as
      biomarkers for monitoring transfluthrin exposure of the general population. After
      a single dose of 26, 64, 160 or 400 mg/kg body weight of transfluthrin had been
      administered intraperitoneally to male Sprague-Dawley rats, their urine was
      collected periodically for one week. Three major urinary transfluthrin
      metabolites were measured: 2,3,5,6-tetrafluorobenzyl alcohol, 2,3,5,6
      tetrafluorobenzoic acid and 3-(2,2-dichlorovinyl)-2,2
      dimethylcyclopropanecarboxylic acid. The kinetics was evaluated by moment
      analysis of the urinary excretion rate of the metabolites versus time curves. The
      urinary excretion amounts of these three metabolites were estimated to be
      proportional to the absorption amounts of transfluthrin over a wide exposure
      range. Urinary 2,3,5,6-tetrafluorobenzoic acid was considered to be an optimal
      biomarker for monitoring transfluthrin exposure.

PMID- 24560338
TI  - Pain in people living with HIV/AIDS: a systematic review.
AB  - INTRODUCTION: Pain is one of the most commonly reported symptoms in people living
      with HIV/AIDS (PLWHA). However, wide ranges of pain prevalence have been
      reported, making it difficult to determine the relative impact of pain in PLWHA.
      A systematic review of the literature was conducted to establish the prevalence
      and characteristics of pain and to explore pain management in PLWHA. METHODS:
      Studies that included cross-sectional data were included in the search, which was
      conducted in April 2012. Databases searched using a time limit of March 1982 to
      March 2012 included PubMed, Scopus, Africa-wide: NIPAD, CINAHL, PsychARTICLES,
      PSYCINFO, PSYCHIATRYONLINE, ScienceDirect and Web of Science. Search terms
      selected were "pain" and "HIV" or "acquired immune deficiency syndrome." Two
      reviewers independently screened all citation abstracts for inclusion.
      Methodological quality was evaluated using a standardized 11-item critical
      appraisal tool. RESULTS: After full text review, 61 studies fulfilled the
      inclusion criteria. Prevalence of pain ranged from a point prevalence of 54%
      (95%CI 51.14-56.09) to 83% (95%CI 76-88) using a three-month recall period. The
      reported pain was of moderate-to-severe intensity, and pain was reported in one
      to two and a half different anatomical sites. Moderate levels of pain
      interference with function were reported. All nine studies reporting on the
      adequacy of pain management recorded marked under-treatment of pain. DISCUSSION:
      The studies reviewed reported that pain commonly presents at multiple pain sites
      with a range of severity suggesting that there are several differing pathological
      processes contributing to pain at one time. The interplay of variables associated
      with pain suggests that the biopsychosocial model of pain is an appropriate
      paradigm from which to view pain in PLWHA and from which to approach the problem,
      explore causes and establish effective treatment. CONCLUSIONS: The results
      highlight that pain is common in PLWHA at all stages of the disease. The
      prevalence rates for pain in PLWHA do not appear to have diminished over the 30
      years spanning the studies reviewed. The body of work available in the literature
      thus far, while emphasizing the problem of pain, has not had an impact on its
      management.

PMID- 24560340
TI  - High levels of anti-Nef antibodies may prevent AIDS disease progression in
      vertically HIV-1-infected infants.
AB  - INTRODUCTION: HIV-1-associated CD4+ T-cell depletion is a consequence of
      uninfected cell death. Nef is one of the viral factors that trigger apoptosis on
      bystander cells, though the plasma Nef levels do not correlate with Th
      lymphocytes counts. The aim of our study was to evaluate whether anti-Nef
      antibodies were involved in paediatric AIDS development and whether they can
      prevent the CD4+ T-cell depletion in vertically infected children. METHODS: Two
      hundred and seventy three HIV-1 vertically infected children seen at Garrahan
      Paediatric Hospital were randomly included in the study, adding 13 selected
      cases: seven LTNP (long-term non-progressors) and six RP (rapid progressors)
      children (n(total)=286). Specific anti-HIV-1-Nef antibodies were titrated by
      indirect ELISA and compared between groups. The plasma blocking effect on Nef
      dependent cytotoxicity was evaluated in Jurkat cells using recombinant Nef as
      apoptotic stimulus and patient plasmas as blockers, measuring the apoptotic
      levels using Annexin-V stain and flow cytometry. RESULTS: Only 63.4% of the
      patients had specific anti-Nef antibodies, and the levels of anti-Nef antibodies
      found in the selected LTNPs plasmas were always significantly higher (p=1.55*10(
      4)) than those in RPs or general HIV-1+ paediatric populations. The LTNPs' plasma
      had a strong inhibitory effect on Nef-dependent cytotoxicity even at high
      dilutions, while RP plasmas had little or no effect on Nef-induced apoptosis.
      DISCUSSION AND CONCLUSIONS: High anti-Nef antibody levels are associated and
      predict slow or non-progression to AIDS in vertically HIV-1-infected children.
      They could be an efficient tool in preventing Nef-associated bystander effect,
      preserving CD4+ T-cells and the immune function in the context of paediatric HIV
      1 infection.

PMID- 24560339
TI  - Sources of HIV incidence among stable couples in sub-Saharan Africa.
AB  - INTRODUCTION: The recent availability of efficacious prevention interventions
      among stable couples offers new opportunities for reducing HIV incidence in sub
      Saharan Africa. Understanding the dynamics of HIV incidence among stable couples
      is critical to inform HIV prevention strategy across sub-Saharan Africa. METHODS:
      We quantified the sources of HIV incidence arising among stable couples in sub
      Saharan Africa using a cohort-type mathematical model parameterized by nationally
      representative data. Uncertainty and sensitivity analyses were incorporated.
      RESULTS: HIV incidence arising among stable concordant HIV-negative couples
      contribute each year, on average, 29.4% of total HIV incidence; of those, 22.5%
      (range: 11.1%-39.8%) are infections acquired by one of the partners from sources
      external to the couple, less than 1% are infections acquired by both partners
      from external sources within a year and 6.8% (range: 3.6%-11.6%) are
      transmissions to the uninfected partner in the couple in less than a year after
      the other partner acquired the infection from an external source. The mean
      contribution of stable HIV sero-discordant couples to total HIV incidence is
      30.4%, with most of those, 29.7% (range: 9.1%-47.9%), being due to HIV
      transmissions from the infected to the uninfected partner within the couple. The
      remaining incidence, 40.2% (range: 23.7%-64.6%), occurs among persons not in
      stable couples. CONCLUSIONS: Close to two-thirds of total HIV incidence in sub
      Saharan Africa occur among stable couples; however, only half of this incidence
      is attributed to HIV transmissions from the infected to the uninfected partner in
      the couple. The remaining incidence is acquired through extra-partner sex.
      Substantial reductions in HIV incidence can be achieved only through a prevention
      approach that targets all modes of HIV exposure among stable couples and among
      individuals not in stable couples.

PMID- 24560341
TI  - The potential for bridging: HIV status awareness and risky sexual behaviour of
      injection drug users who have non-injecting permanent partners in Ukraine.
AB  - OBJECTIVE: To quantify potential bridging of HIV transmission between the
      injection drug using subpopulation to the non-injection drug using population
      through unprotected heterosexual sex. DESIGN: Secondary analysis of cross
      sectional data. METHODS: A sub-sample of participants who reported having a
      permanent partner who are not injection drug users and have not injected drugs in
      the past (N=1379) was selected from a survey implemented in 26 Ukrainian cities
      in 2011. This study evaluates the association between consistent condom use and
      awareness of HIV status as measured by rapid testing during the study
      (known/unknown HIV+, known/unknown HIV- and undetermined) among a sub-sample of
      male injection drug users (IDUs) who have a non-injecting permanent partner.
      Poisson regression, with robust variance estimates, was utilized to identify
      associations while adjusting for other factors. RESULTS: Reported consistent
      condom use varied between 15.5% (unknown HIV-) and 37.5% (known HIV+); average
      use was 19.3%. In multivariate analysis, males who were aware of their HIV+
      status were more likely to report recent consistent condom use compared to those
      who were unaware of their HIV+ status. This association remains after adjustment
      for age, region, education level, years of injection, alcohol use, self-reported
      primary drug use and being an NGO client (prevalence ratio=1.65; 95% CI 1.03
      2.64). No such association was found for those who were HIV-. CONCLUSIONS: Our
      results regarding HIV-positive male IDUs reinforce previous findings that HIV
      testing and counselling may be an effective means of secondary prevention.
      Further research is needed to understand how to effectively promote safer sex
      behaviours for IDUs who are currently HIV-.

PMID- 24560343
TI  - Is rapid withdrawal of anti-epileptic drug therapy during video EEG monitoring
      safe and efficacious?
AB  - PURPOSE: Video electroencephalographic monitoring (VEM) is used to record ictal
      and interictal epileptiform activity and to ascertain the level of concordance
      between the two. Often, taper or discontinuation of anti-epileptic (AED) therapy
      is needed to facilitate seizure occurrence. The safety of this practice is
      unclear and long-term sequelae have yet to be elucidated. METHODS: This is a
      prospective study of 158 patients subjected to combined sleep-deprived VEM with
      rapid AED withdrawal, for evaluation of seizure-like episodes over 24 months
      under the care of an epileptologist with direct nursing observation and EEG
      technician support in our telemetry unit. In most cases, AEDs were discontinued
      within 24h of admission. We assessed the diagnostic yield and safety of VEM as
      well as epilepsy surgery outcomes. RESULTS: VEM answered the study question in
      90.5% of cases but failed to record ictal events in 9.5%. This diagnostic yield
      was achieved over a mean VEM duration of 4.53+/-1.44 days, with no benefit of
      longer monitoring. These findings improved quality of life by optimizing medical
      and surgical therapeutic planning, leading to improved seizure control. Overall,
      32.9% of the cohort received epilepsy surgery. The complication rate was 5.06%,
      characterized largely by musculoskeletal pain secondary to clinical seizure
      activity, with no mortality observed. In the first month following VEM 2.5% of
      patients received emergency-room admission for seizure clustering. CONCLUSIONS:
      VEM with combined sleep deprivation and protocolized rapid AED withdrawal is a
      safe and effective investigative technique with no adverse long-term sequelae. It
      is a reliable strategy for therapeutic planning and can be used to determine
      candidacy for surgical treatment.

PMID- 24560342
TI  - Intimate partner violence and HIV infection among women: a systematic review and
      meta-analysis.
AB  - INTRODUCTION: To assess evidence of an association between intimate partner
      violence (IPV) and HIV infection among women. METHODS: Medline/PubMed, Embase,
      Web of Science, EBSCO, Ovid, Cochrane HIV/AIDS Group's Specialized Register and
      Cochrane Central Register of Controlled Trials were searched up to 20 May 2013 to
      identify studies that examined the association between IPV and HIV infection in
      women. We included studies on women aged >=15 years, in any form of sexually
      intimate relationship with a male partner. RESULTS: Twenty-eight studies [(19
      cross-sectional, 5 cohorts and 4 case-control studies) involving 331,468
      individuals in 16 countries - the US (eight studies), South Africa (four
      studies), East Africa (10 studies), India (three studies), Brazil (one study) and
      multiple low-income countries (two studies)] were included. Results were pooled
      using RevMan 5.0. To moderate effect estimates, we analyzed all data using the
      random effects model, irrespective of heterogeneity level. Pooled results of
      cohort studies indicated that physical IPV [pooled RR (95% CI): 1.22 (1.01,
      1.46)] and any type of IPV [pooled RR (95% CI): 1.28 (1.00, 1.64)] were
      significantly associated with HIV infection among women. Results of cross
      sectional studies demonstrated significant associations of physical IPV with HIV
      infection among women [pooled OR (95% CI): 1.44 (1.10, 1.87)]. Similarly, results
      of cross-sectional studies indicated that combination of physical and sexual IPV
      [pooled OR (95% CI): 2.00 (1.24, 3.22) and any type of IPV [pooled OR (95% CI):
      1.41 (1.16, 1.73)] were significantly associated with HIV infection among women.
      CONCLUSIONS: Available evidence suggests a moderate statistically significant
      association between IPV and HIV infection among women. To further elucidate the
      strength of the association between IPV and HIV infection among women, there is a
      need for high-quality follow-up studies conducted in different geographical
      regions of the world, and among individuals of diverse racial/cultural
      backgrounds and varying levels of HIV risks.

PMID- 24560344
TI  - miRNA expression analysis in cortical dysplasia: regulation of mTOR and LIS1
      pathway.
AB  - Cortical dysplasia (CD) is a common cause of epilepsy in children and is
      characterized by focal regions of malformed cerebral cortex. The pathogenesis and
      epileptogenesis of CD have not been fully elucidated, and in particular, the
      potential role of epigenetics has not been examined. miRNA microarray was
      performed on surgical specimens from CD (n=8) and normal control (n=2) children.
      A total of 10 differentially expressed miRNAs (DEmiRs) that were up-regulated in
      CD were identified including hsa-miR-21 and hsa-miR-155. The microarray results
      were validated using quantitative real-time PCR. After searching for the putative
      target genes of the DEmiRs, their biological significance was further evaluated
      by exploring the pathways in which the genes were enriched. The mammalian target
      of rapamycin (mTOR) signaling pathway was the most significantly associated, and
      the pathway of lissencephaly gene in neuronal migration and development was also
      noted. This study suggests a possible role for miRNAs in the pathogenesis of CD,
      especially in relation to the mTOR signaling pathway. Future studies on the
      epigenetic mechanisms underlying CD pathogenesis and epileptogenesis are needed. 

PMID- 24560346
TI  - Female sterilization and refertilization.
AB  - OBJECTIVE: To analyze data on sterilization and refertilization procedures that
      took place at Orbis Medical Center in Sittard, a hospital in the south of the
      Netherlands. STUDY DESIGN: Retrospective cohort study of surgical tubal
      sterilizations performed on 966 patients for contraception between 2002 and 2011,
      and of 19 patients who underwent refertilization between 2002 and 2012. The main
      outcome measures were complications and failure rates of sterilization, motives
      for refertilization and pregnancy rates after refertilization. The t test and
      nonparametric tests were used to determine differences between groups and
      proportions. RESULTS: Between 2002 and 2011, the number of sterilizations
      declined. Almost all the patients (99.8%) underwent laparoscopic sterilization.
      The most common method of sterilization used Filshie clips, and was used in 99.7%
      of the women. The median age at the time of sterilization was 37 years. The
      failure rate was 0.3%. All procedures were uneventful. The number of
      refertilizations during this time period also declined. The median time between
      sterilization and refertilization was 65 months. Patients who underwent
      refertilization were significantly younger at time of sterilization than patients
      who did not (p<0.001). After refertilization, 12 patients (63.2%) became
      pregnant. CONCLUSIONS: The complication and failure rates of laparoscopic
      sterilization are low. The number of laparoscopic sterilizations and the number
      of refertilizations are both declining. Still, refertilization is a safe
      procedure and gives a significant chance of becoming pregnant.

PMID- 24560347
TI  - The female Homo pelvis from Gona: response to Ruff (2010).

PMID- 24560345
TI  - Toxoplasma gondii Hsp90: potential roles in essential cellular processes of the
      parasite.
AB  - Hsp90 is a widely distributed and highly conserved molecular chaperone that is
      ubiquitously expressed throughout nature, being one of the most abundant proteins
      within non-stressed cells. This chaperone is up-regulated following stressful
      events and has been involved in many cellular processes. In Toxoplasma gondii,
      Hsp90 could be linked with many essential processes of the parasite such as host
      cell invasion, replication and tachyzoite-bradyzoite interconversion. A Protein
      Protein Interaction (PPI) network approach of TgHsp90 has allowed inferring how
      these processes may be altered. In addition, data mining of T. gondii
      phosphoproteome and acetylome has allowed the generation of the phosphorylation
      and acetylation map of TgHsp90. This review focuses on the potential roles of
      TgHsp90 in parasite biology and the analysis of experimental data in comparison
      with its counterparts in yeast and humans.

PMID- 24560348
TI  - Metastasis of primary lung carcinoma to the breast: a systematic review of the
      literature.
AB  - BACKGROUND: The purpose of this systematic review was to summarize previously
      published case reports of primary lung carcinoma metastasis to the breast to
      assess common clinical and pathologic features and management strategies.
      MATERIALS AND METHODS: Case reports describing breast metastasis of primary lung
      carcinoma were systematically evaluated in MEDLINE and EMBASE. RESULTS: Thirty
      one reported cases of non-small-cell lung carcinoma (NSCLC) metastasized to the
      breast were identified, along with eight cases of small-cell lung carcinoma.
      Sixty-seven percent of reported NSCLC metastases to the breast were detected
      metachronously with the primary lung abnormality, whereas 80% of small-cell lung
      carcinoma breast metastases appeared synchronously. Thyroid transcription factor
      1 was found to be expressed in 58% of total NSCLC breast metastases, including
      83% of those of adenocarcinoma origin. Therapeutic strategies among NSCLC cases
      varied widely, and only 36% of NSCLC breast metastasis patients were administered
      chemotherapy. Additional sites of metastasis in these cases are summarized as
      well. CONCLUSIONS: It is recommended to include metastatic lung cancer in the
      differential diagnosis of patients presenting with a breast abnormality in the
      context of a suspected lung cancer. Thyroid transcription factor 1 expression
      should be examined in these cases. The metachronous versus synchronous nature of
      lung carcinoma metastasis to the breast has consequences for both detection of
      the primary and secondary lesions and patient outlook. Clinical correlation is
      vital to effective management of the care of patients harboring these atypical
      secondary lesions.

PMID- 24560349
TI  - Contribution of human adipose tissue-derived stem cells and the secretome to the
      skin allograft survival in mice.
AB  - BACKGROUND: Despite considerable evidence showing the immunosuppressive
      properties of mesenchymal stem cells (MSCs) in vitro, such properties have not
      been fully demonstrated in vivo. The aim of this study was to evaluate the effect
      of MSCs and/or MSC secretome in inducing tolerance in a mouse skin
      transplantation model. METHODS: After receiving full-thickness skin
      allotransplantation on the back of the mouse, the recipient mice were infused
      with phosphate-buffered saline, adipose tissue-derived stem cells (ASCs),
      conditioned media (CM), and control media. Specifically, ASCs (1.0 * 10(6)/0.1
      mL) were transplanted to ASC-infused mice and 25-fold concentrated CM, which had
      been obtained from ASC culture were infused to CM-infused mice. Graft survival
      rates and the parameters reflecting immunologic consequences were assessed.
      RESULTS: The serum level of proinflammatory cytokine interleukin 6 decreased in
      mice treated with ASCs or CM compared with the control groups after infusion (P <
      0.05). Interferon gamma, interleukin 10, and tumor necrosis factor alpha
      messenger RNA levels in the skin graft seemed to be decreased in the ASC-infused
      mice and CM-infused mice. Hyporesponsiveness was identified in mixed lymphocyte
      reaction assay at 30-d posttransplantation in ASC- or CM-infused mice. And,
      administering ASCs and CM markedly increased skin allograft survival compared
      with control animals (P < 0.001). CONCLUSIONS: These findings suggest that ASCs
      and their secretome have the potential to induce immunologic tolerance. Moreover,
      our results demonstrate that the immunosuppressive properties of ASCs are
      mediated by the ASC secretome. Our approach could provide insights into a
      promising strategy to avoid toxicities of chemical immunosuppressive regimen in
      solid organ transplantation.

PMID- 24560350
TI  - Shockwave therapy improves anterior cruciate ligament reconstruction.
AB  - BACKGROUND: Shockwave was shown to enhance the healing of anterior cruciate
      ligament (ACL) reconstruction in rabbits. This study evaluated the effect of
      extracorporeal shockwave therapy (ESWT) on ACL reconstruction in human subjects.
      We hypothesized that ESWT may improve human ACL reconstruction. METHODS: Fifty
      three patients were randomized into two groups with 26 patients in ESWT group and
      27 patients in control group. The ESWT group underwent single-bundle hamstring
      autograft ACL reconstruction and received ESWT immediately after surgery. The
      control group underwent ACL surgery without ESWT. Both groups received the same
      rehabilitation postoperatively. The evaluations included Lysholm score, IKDC
      score and KT-1000, radiograph, bone mineral density, and magnetic resonance
      imaging. RESULTS: ESWT group showed significantly better Lysholm score than
      control group at 1 and 2 y postoperatively (P < 0.001 and 0.001, respectively).
      No significant difference was noted in IKDC score between the two groups (P =
      0.080 and 0.076, respectively). The KT-1000 values were significantly better in
      ESWT group than control group at 2 y postoperatively (P = 0.027). The tibia
      tunnel on X-ray was significantly smaller in ESWT group compared with control
      group at 2 y (P = 0.018). The bone mineral density values showed no discernable
      difference between the two groups at 6 mo and 2 y (P = 0.522 and 0.984,
      respectively). On magnetic resonance imaging, ESWT group showed significant
      decrease in tibia tunnel enlargement at 6 mo and 2 y compared with the control
      group (P = 0.024 and <0.001, respectively). CONCLUSIONS: ESWT significantly
      improves the subjective Lysholm score and decreases the middle 1/3 tibia tunnel
      enlargement after single hamstring autograft ACL reconstruction.

PMID- 24560351
TI  - Segmentation studies provide insights to better understanding attitudes towards
      science and technology.
AB  - Values-based studies of people's attitudes towards science and technology not
      only provide great insights into what drives different attitudes to issues like
      climate change and genetically modified foods, but allow for segmenting the
      general public by homogeneous values. Such segmentations both provide better
      predictions of people's attitudes to new technologies or contentious science
      issues than age, sex, or other standard demographics, and allow a better matching
      of different messages with different community values. 

PMID- 24560352
TI  - Etoposide loaded solid lipid nanoparticles for curtailing B16F10 melanoma
      colonization in lung.
AB  - Poor solubility of etoposide and associated poor bioavailability of the drug was
      circumvented by developing solid lipid nanocarrier system. The objective of the
      research work was to prepare etoposide loaded solid lipid nanoparticles (SLN) for
      improved efficacy and therapy of metastasized cancers. Entrapment of drug into
      nanoparticulate system modifies the pharmacokinetic and biodistribution profile
      of the drug with improved therapeutic efficacy. Solid lipid nanoparticles of
      various triglycerides were prepared using hot homogenization technique. Further,
      the process and formulation parameters viz. homogenization cycle and pressure,
      type of lipid were optimized. Developed nanoparticles were characterised for
      particle size, in vitro dissolution studies, DSC thermogram, surface morphology
      and cytotoxicity assay. Pharmacokinetic and biodistribution study were performed
      to assess the distribution of the drug in vivo. Modulation of the therapeutic
      activity of the drug was studied by performing antimetastatic activity on a
      B16F10 melanoma mouse model. The obtained results exhibited suitability of
      trimysristin for fabrication of nanoparticles. Characterisation of nanoparticles
      depicted formation of homogenous, spherical particles entrapping approximately
      50% of the drug. The results for the performed MTT assay suggested that the
      developed nanoparticles exhibited cytotoxicity in a time- and concentration
      dependent fashion. These findings concord with the results of the in vitro
      dissolution profile. Pharmacokinetic parameters demonstrated increase in area
      under curve (AUC), t1/2 and mean residence time (MRT) for drug in plasma. Further
      there is enhancement in the ratio of the drug that reaches to the highly perfused
      organs (upon encapsulation into solid lipid nanoparticles). Generally, cancer
      cells metastasized through the blood or lymphatic system. Accumulation of the
      drug in the highly perfused organ suggests suitability of the developed
      nanoparticles for targeting metastasized tumors. This was proved by the findings
      of the in vivo B16F10 mouse melanoma model. Improvement in the tumoricidal
      activity and survival rate of the animals substantiates the application of
      nanoparticles for improved therapeutic activity of etoposide. 

PMID- 24560353
TI  - Rapid and sensitive method for the determination of polycyclic aromatic
      hydrocarbons in soils using pseudo multiple reaction monitoring gas
      chromatography/tandem mass spectrometry.
AB  - A method for the rapid determination of 18 polycyclic aromatic hydrocarbons
      (PAHs) in soil has been established based on a simplified solvent extraction and
      GC/MS/MS operated in pseudo multiple reaction monitoring mode (PMRM), a technique
      where the two quadrupoles mass monitor the same m/z. The PMRM approach proved
      superior to the classic single quadrupole technique, with enhanced sensitivity,
      specificity, and significant reduction in time consuming sample clean-up
      procedures. Trace level PAHs could be readily confirmed by their retention times
      and characteristic ions. The limit of quantitation in soil was observed to be
      20ng/g for 16 EPA-priority PAHs and 2 additional PAHs specific to Environment
      Canada. The developed method was linear over the calibration range 20-4000ng/g in
      soil, with observed coefficients of determination of >0.996. Individual PAH
      recoveries from fortified soil were in the range 58.1 to 110.1%, with a precision
      between 0.3 and 4.9% RSD. The ruggedness of the method was demonstrated by the
      success of an inter-lab proficiency test study organized by the Canadian
      Association for Laboratory Accreditation. The present method was found to be
      applicable as a rapid, routine screening for PAH contamination in soil, with
      significant savings in terms of preparation time and solvent usage. 

PMID- 24560354
TI  - The effects of environmental chemical carcinogens on the microRNA machinery.
AB  - The first evidence that microRNA expression is early altered by exposure to
      environmental chemical carcinogens in still healthy organisms was obtained for
      cigarette smoke. To date, the cumulative experimental data indicate that similar
      effects are caused by a variety of environmental carcinogens, including
      polycyclic aromatic hydrocarbons, nitropyrenes, endocrine disruptors, airborne
      mixtures, carcinogens in food and water, and carcinogenic drugs. Accordingly, the
      alteration of miRNA expression is a general mechanism that plays an important
      pathogenic role in linking exposure to environmental toxic agents with their
      pathological consequences, mainly including cancer development. This review
      summarizes the existing experimental evidence concerning the effects of chemical
      carcinogens on the microRNA machinery. For each carcinogen, the specific microRNA
      alteration signature, as detected in experimental studies, is reported. These
      data are useful for applying microRNA alterations as early biomarkers of
      biological effects in healthy organisms exposed to environmental carcinogens.
      However, microRNA alteration results in carcinogenesis only if accompanied by
      other molecular damages. As an example, microRNAs altered by chemical carcinogens
      often inhibits the expression of mutated oncogenes. The long-term exposure to
      chemical carcinogens causes irreversible suppression of microRNA expression thus
      allowing the transduction into proteins of mutated oncogenes. This review also
      analyzes the existing knowledge regarding the mechanisms by which environmental
      carcinogens alter microRNA expression. The underlying molecular mechanism
      involves p53-microRNA interconnection, microRNA adduct formation, and alterations
      of Dicer function. On the whole, reported findings provide evidence that microRNA
      analysis is a molecular toxicology tool that can elucidate the pathogenic
      mechanisms activated by environmental carcinogens. 

PMID- 24560355
TI  - Mitochondrial cardiomyopathy: an exceptional cause of cardiac hypertrophy.

PMID- 24560356
TI  - A rare pediatric case of pancreatic tuberculosis with veinous thrombosis.

PMID- 24560357
TI  - Exploring the medical home in Ryan White HIV care settings: a pilot study.
AB  - Amid increased attention to the cost of health care, health information
      technology, and specialization and fragmentation in medicine, the medical home
      has achieved recognition as a model for more effective and efficient health care.
      Little data are available on recently funded HIV medical home demonstration
      projects, and no research richly describes existing medical home characteristics,
      implementation challenges, and impact on outcomes in longstanding HIV outpatient
      settings. The Ryan White HIV/AIDS Program (RWP) provides federal funding for
      primary and specialty care for people living with HIV. Although RWP clinics
      developed independently of the medical home model, existing data indirectly
      support that, with emphasis on primary, comprehensive, and patient-centered care,
      RWP clinics operate as medical homes. This study explores the development,
      definition, and implementation of medical home characteristics by RWP-funded
      providers in order to better understand how it fits with broader debates about
      medical homes and health care reform.

PMID- 24560359
TI  - A retrospective analysis of the effectiveness of low molecular weight heparin for
      venous thromboembolism prophylaxis in trauma patients.
AB  - BACKGROUND: In trauma patients, Enoxaparin (a low molecular weight heparin, LMWH)
      prophylaxis for venous thromboembolism (VTE) risk reduction is unproven. METHODS:
      Cohort analysis conducted consisting of all trauma patients age >13 admitted to
      Level-I trauma center and hospitalized >48 hours. VTE risk determined by the Risk
      Assessment Profile. High risk patients received LMWH unless contraindicated,
      while low and moderate risk patients received LMWH at attending surgeon's
      discretion. Odds ratio for VTE by logistic regression. VTE incidence, relative
      risk (RR), and number needed to treat (NNT) to prevent deep vein thrombosis (DVT)
      or pulmonary embolism determined by risk category. RESULTS: Cohort consisted of
      2,281 patients (1,211 low, 979 moderate, 91 high risks). VTE occured in 254
      patients (11.1%). High-risk patients had significantly higher VTE incidence, odds
      ratio = 31.8 (P < .001). VTE was significantly reduced in high-risk patients
      receiving LMWH versus those who did not (.26 vs .53, P = .02). Among moderate and
      high risk, prophylactic LMWH reduced the incidence of pulmonary embolism (RR =
      .19, NNT = 40.4, P = .01), and trended toward reduced DVT incidence (RR = .81,
      NNT = 27.3, P = .15). LMWH lowered DVT incidence (RR = .52, NNT = 4.1, P = .03)
      in high risk patients. CONCLUSION: Prophylactic LMWH is associated with reduction
      of VTE in trauma patients.

PMID- 24560358
TI  - A comparison of medication management between older and younger adults living
      with HIV.
AB  - The aims of this study were to examine differences in medication management
      between older and younger adults living with HIV and to examine the relationship
      between age and cognitive ability, depressive symptoms, and self-efficacy on
      medication management. This research utilized a descriptive-correlational, cross
      sectional design to compare medication management between older and younger
      adults living with HIV and to describe differences in predictive factors of
      cognition, depressive symptoms, and self-efficacy on medication management.
      Results indicated that both older and younger adults had poor medication
      management skills and high rates of mild cognitive impairment. While older adults
      performed worse on the medication management test than younger adults, the
      results were not statistically significant. In both older and younger adults,
      cognitive ability and depressive symptoms were predictors of medication
      management, with cognitive ability being the strongest predictor for both groups.
      Cognitive ability was a stronger predictor for older adults than for younger
      adults. 

PMID- 24560360
TI  - A booming economy means a bursting trauma system: association between hospital
      admission for major injury and indicators of economic activity in a large
      Canadian health region.
AB  - BACKGROUND: Injury epidemiology fluctuates with economic activity in many
      countries. These relationships remain unclear in Canada. METHODS: The annual risk
      of admission for major injury (Injury Severity Score >=12) to a high-volume,
      level-1 Canadian trauma center was compared with indicators of economic activity
      over a 16-year period using linear regression. RESULTS: An increased risk of
      injured patient admissions was associated with rising mean gross domestic product
      (GDP [millions of chained 2002 dollars]) (.36 person increase per 100,000
      population/$1,000 increase in GDP; P = .001) and annual gasoline prices (.47
      person increase per 100,000 population/cent increase in gasoline price; P =
      .001). Recreation-related vehicle injuries were also associated with economic
      affluence. The risk of trauma patient mortality with increasing mean annual GDP
      (P = .72) and gasoline prices (P = .32) remained unchanged. CONCLUSION: Hospital
      admissions for major injury, but not trauma patient mortality, were associated
      with economic activity in a large Canadian health care region.

PMID- 24560361
TI  - Peritumoral deposits: complicating the colorectal cancer staging system.

PMID- 24560362
TI  - Monitoring of intracranial pressure and cerebral hemodynamics by transjugular
      dural sinus catheterization.
AB  - Cerebral venous sampling may be useful in the evaluation of cerebral damage. A
      catheter was successfully inserted 18 cm deep from the right internal jugular
      vein into the transverse sinus in a 38 year old man with B-mode ultrasound
      guidance to measure pressure and sample blood. Transverse sinus venous oxygen
      saturation (StvO2) was lower than normal ranges (55% - 75%) for jugular venous
      oxygen saturation (SjvO2). At the time spontaneous cardiac rhythm was restored,
      transverse sinus pressure increased briefly to 26 mmHg [more than 15 mmHg higher
      than normal intracranial pressure (ICP)]. This case suggests that catheterization
      of the dural sinus may be accomplished with B-mode ultrasound guidance and that
      the catheter can be used to monitor ICP and cerebral hemodynamics. 

PMID- 24560364
TI  - First report of fluazuron resistance in Rhipicephalus microplus: a field tick
      population resistant to six classes of acaricides.
AB  - The control of the cattle tick Rhipicephalus microplus is based mainly on the use
      of chemical acaricides, which has contributed to the emerging problem of
      selection of resistant tick populations. Currently, there are six main classes of
      acaricides commercially available in Brazil to control cattle ticks, with
      fluazuron, a tick growth regulator with acaricidal properties, being the only
      active ingredient with no previous reports of resistance. Ticks (designated the
      Jaguar strain) were collected in a beef cattle ranch located at Rio Grande do Sul
      state, Southern Brazil, after a complaint of fluazuron treatment failure. To
      characterise the resistance of this strain against acaricides, larval tests were
      performed and showed that the Jaguar strain was resistant to all of the drugs
      tested: cypermethrin (resistance ratio, RR=31.242), chlorpyriphos (RR=103.926),
      fipronil (RR=4.441), amitraz (RR=11.907) and ivermectin (3.081). A field trial
      was conducted to evaluate the efficacy of fluazuron treatment in heifers that had
      been experimentally infested with the Jaguar or a susceptible strain. Between 14
      and 28 days after treatment, the average efficacy in cattle experimentally
      infested with the susceptible strain was 96%, while for the Jaguar strain the
      efficacy was zero. Additionally, the Jaguar strain response to fluazuron was
      evaluated in vitro using a modified adult immersion test (AIT) and the artificial
      feeding assay (AFA). With the AIT, 50 ppm of fluazuron inhibited 99% of larvae
      hatching in the susceptible strain (POA) and less than 50% in the Jaguar strain.
      Results of the AFA showed a larval hatching rate of 67% at 2.5 ppm of fluazuron
      with the Jaguar strain; conversely, only 3% of larvae of the susceptible strain
      hatched at the same fluazuron concentration. The results showed here demonstrated
      the first case of fluazuron resistance in R. microplus and the first tick
      population resistant to six classes of acaricides in Brazil.

PMID- 24560365
TI  - Anthelmintic resistance and multidrug resistance in sheep gastro-intestinal
      nematodes in France, Greece and Italy.
AB  - Anthelmintic resistance (AR) in ovine gastro-intestinal nematodes has been
      reported to affect the health and productivity of sheep globally. The objective
      of the present study was to evaluate the efficacy of commonly used oral drenches
      in sheep in France, Greece and Italy. In each country, 10 farms were selected. On
      each farm, 50 animals were blocked based on the pre-treatment faecal egg count
      (FEC). Within each block, animals were randomly allocated to one of 5 treatment
      groups. In addition to an untreated control group, there were 4 groups treated
      per oral route: moxidectin (MOX) and ivermectin (IVM), both at 0.2mg/kg
      bodyweight, levamisole (LEV; at 7.5mg/kg bodyweight) and a benzimidazole (BZ; at
      3.75-5mg/kg bodyweight). In France, animals were not treated with LEV, but with
      netobimin (NET; at 7.5mg/kg bodyweight). The FEC was monitored using a modified
      McMaster technique. Two weeks after treatment, individual faecal samples were
      taken from all animals and efficacy was calculated as the difference between
      arithmetic mean FEC of the control group versus each respective treatment group.
      The results of the present study indicate the high efficacy of treatment with
      oral formulations of MOX (99-100%) and IVM (98-100%) on all farms, except on 1
      farm in Greece. On this farm, multi drug resistance (MDR) was identified
      involving 4 anthelmintics (efficacy MOX: 91%; IVM: 0%; BZ: 58% and LEV: 87%). In
      Greece and Italy, AR against LEV and BZ was observed on some farms, with MDR
      involving both anthelmintics on 3 farms in Greece and on 2 farms in Italy. In
      France, AR against BZ and NET was observed on all 10 farms included. In all
      countries, Teladorsagia sp. was the most common nematode larva identified after
      treatment, followed by Haemonchus sp. and Trichostrongylus sp., with differences
      among farms and treatments. The current study confirms the high efficacy of oral
      treatments with MOX and IVM, even on farms with worm populations resistant to BZ,
      LEV or NET. This study also reports MDR against 4 anthelmintics on one farm in
      Greece. 

PMID- 24560366
TI  - Case report: First confirmed case of canine peritoneal larval cestodiasis caused
      by Mesocestoides vogae (syn. M. corti) in Japan.
AB  - Canine peritoneal larval cestodiasis (CPLC) is an unusual parasitic disease in
      dogs that is caused by asexual proliferation of larval Mesocestoides. A 12 year
      old spayed Shetland sheepdog with abdominal distension was referred to the Animal
      Medical Center at Nihon University, Japan. The presence of ascites was confirmed
      by abdominal ultrasonography and X-ray imaging. In addition, a number of
      parasites were observed in the ascitic fluid collected by abdominal paracentesis.
      Each of the whitish colored parasites was less than 1mm in size. The parasites
      were morphologically identified as Mesocestoides sp. tetrathyridia. The parasites
      had four suckers and calcareous corpuscles, but no hooks or rostellum.
      Mitochondrial (mt) 12S rDNA and mt cytochrome c oxidase subunit 1 DNA amplified
      from the tetrathyridia were used for molecular identification to species level.
      DNA sequence analysis showed that the tetrathyridia shared more than 99% identity
      with M. vogae (syn. M. corti) for each gene. The patient was treated with a
      standard dose (5mg/kg) of praziquantel, which was administered subcutaneously
      twice at an interval of 14 days. This resulted in successful deworming. This is
      the first case that CPLC was diagnosed in a dog that had never been taken outside
      of Japan, indicating that M. vogae is distributed in this country.

PMID- 24560367
TI  - Review of online coupling of sample preparation techniques with liquid
      chromatography.
AB  - Sample preparation is still considered as the bottleneck of the whole analytical
      procedure, and efforts has been conducted towards the automation, improvement of
      sensitivity and accuracy, and low comsuption of organic solvents. Development of
      online sample preparation techniques (SP) coupled with liquid chromatography (LC)
      is a promising way to achieve these goals, which has attracted great attention.
      This article reviews the recent advances on the online SP-LC techniques. Various
      online SP techniques have been described and summarized, including solid-phase
      based extraction, liquid-phase-based extraction assisted with membrane, microwave
      assisted extraction, ultrasonic assisted extraction, accelerated solvent
      extraction and supercritical fluids extraction. Specially, the coupling
      approaches of online SP-LC systems and the corresponding interfaces have been
      discussed and reviewed in detail, such as online injector, autosampler combined
      with transport unit, desorption chamber and column switching. Typical
      applications of the online SP-LC techniques have been summarized. Then the
      problems and expected trends in this field are attempted to be discussed and
      proposed in order to encourage the further development of online SP-LC
      techniques. 

PMID- 24560368
TI  - Highly enhanced electrochemiluminescent strategy for tumor biomarkers detection
      with in situ generation of L-homocysteine for signal amplification.
AB  - In this work, an ultrasensitive peroxydisulfate electrochemiluminescence (ECL)
      immunosensor using in situ generation of L-homocysteine (L-Hcys) for signal
      amplification was successfully constructed for detection of carcinoembryonic
      antigen (CEA). In the reaction of biological methylation, S-adenosyl-L
      homocysteine hydrolase (SAHH) catalyzed the reversible hydrolysis of S-adenosyl-L
      homocysteine (SAH) to produce L-Hcys, which was inducted into ECL system to
      construct the immunosensor for signal amplification in this work. Simultaneously,
      Gold and palladium nanoparticles functionalized multi-walled carbon nanotubes (Au
      PdNPs@MWCNTs) were prepared, which were introduced to immobilize the secondary
      antibody (Ab2) and SAHH with high loading amount and good biological activity due
      to their improved surface area and excellent biocompatibility. Then the proposed
      ECL immunosensor was developed by a sandwich-type format using Au-PdNPs@MWCNTs
      SAHH-Ab2 as tracer and graphene together with AuNPs as substrate. Besides the
      enhancement of Au-PdNPs, the enzymatic catalysis reaction also amplified the ECL
      signal dramatically, which was achieved by efficient catalysis of the SAHH
      towards the hydrolysis of SAH to generate improved amount of L-Hcys in situ.
      Furthermore, due to the special interaction between Au-PdNPs and -SH or -NH2 in L
      Hcys, L-Hcys would gradually accumulate on the surface of the immunosensor, which
      greatly enhanced the concentration of L-Hcys on the immunosensor surface and
      further improved the ECL intensity. With the amplification factors above, a wide
      linear ranged from 0.1 pg mL(-1) to 80 ng mL(-1) was acquired with a relatively
      low detection limit of 33 fg mL(-1) for CEA.

PMID- 24560369
TI  - Design of functional guanidinium ionic liquid aqueous two-phase systems for the
      efficient purification of protein.
AB  - A series of novel cationic functional hexaalkylguanidinium ionic liquids and
      anionic functional tetraalkylguanidinium ionic liquids have been devised and
      synthesized based on 1,1,3,3-tetramethylguanidine. The structures of the ionic
      liquids (ILs) were confirmed by (1)H nuclear magnetic resonance ((1)H NMR) and
      13C nuclear magnetic resonance (13C NMR) and the production yields were all above
      90%. Functional guanidinium ionic liquid aqueous two-phase systems (FGIL-ATPSs)
      have been first designed with these functional guanidinium ILs and phosphate
      solution for the purification of protein. After phase separation, proteins had
      transferred into the IL-rich phase and the concentrations of proteins were
      determined by measuring the absorbance at 278 nm using an ultra violet visible
      (UV-vis) spectrophotometer. The advantages of FGIL-ATPSs were compared with
      ordinary ionic liquid aqueous two-phase systems (IL-ATPSs). The proposed FGIL
      ATPS has been applied to purify lysozyme, trypsin, ovalbumin and bovine serum
      albumin. Single factor experiments were used to research the effects of the
      process, such as the amount of ionic liquid (IL), the concentration of salt
      solution, temperature and the amount of protein. The purification efficiency
      reaches to 97.05%. The secondary structure of protein during the experimental
      process was observed upon investigation using UV-vis spectrophotometer, Fourier
      transform infrared spectroscopy (FT-IR) and circular dichroism spectrum (CD
      spectrum). The precision, stability and repeatability of the process were
      investigated. The mechanisms of purification were researched by dynamic light
      scattering (DLS), determination of the conductivity and transmission electron
      microscopy (TEM). It was suggested that aggregation and embrace phenomenon play a
      significant role in the purification of proteins. All the results show that FGIL
      ATPSs have huge potential to offer new possibility in the purification of
      proteins.

PMID- 24560370
TI  - Impact of calibrator concentrations and their distribution on accuracy of
      quadratic regression for liquid chromatography-mass spectrometry bioanalysis.
AB  - Despite the common use of quadratic regression in LC-MS bioanalysis, how
      calibrator concentrations should be determined is still vague. Both the number
      and concentrations of calibrators are usually selected arbitrarily to each one's
      preference. The purposes of this research were to evaluate the impact of
      calibrator concentrations and to find new approaches with improved accuracy and
      reduced cost for LC-MS bioanalysis. It was found for the first time that the
      lower and upper limits of quantitation plus their geometric mean are the three
      critical concentrations for quadratic regression. When different concentration
      ranges, different response precisions, and various degrees of downward quadratic
      responses were simulated, the best accuracy was obtained by including these
      critical concentrations and using fewer calibrator concentrations with more
      replicates per concentration, instead of using more calibrator concentrations in
      duplicate. In many cases, when the aforementioned three concentrations are used,
      as few as two replicates per concentration are enough for routine use and up to
      20% of time and cost can be saved. Furthermore, downward quadratic response
      should be eliminated or reduced as much as possible and upper limit quality
      control must be included in each batch to monitor the accuracy at the high
      concentration end. The retrospective data analysis of published experimental
      results corroborates the aforementioned findings. Finally, the typical "concerns"
      and potential applications of the new quadratic regression approaches are
      discussed. 

PMID- 24560371
TI  - Amperometric carbohydrate antigen 19-9 immunosensor based on three dimensional
      ordered macroporous magnetic Au film coupling direct electrochemistry of
      horseradish peroxidase.
AB  - A sandwich-type electrochemical immunosensor for the detection of carbohydrate
      antigen 19-9 (CA 19-9) antigen based on the immobilization of primary antibody
      (Ab1) on three dimensional ordered macroporous magnetic (3DOMM) electrode, and
      the direct electrochemistry of horseradish peroxidase (HRP) that was used as both
      the label of secondary antibody (Ab2) and the blocking reagent. The 3DOMM
      electrode was fabricated by introducing core-shell Au-SiO2@Fe3O4 nanospheres onto
      the surface of three dimensional ordered macroporous (3DOM) Au electrode via the
      application of an external magnet. Au nanoparticles functionalized SBA-15 (Au@SBA
      15) was conjugated to the HRP labeled secondary antibody (HRP-Ab2) through the Au
      SH or Au-NH3(+) interaction, and HRP was also used as the block reagent. The
      formation of antigen-antibody complex made the combination of Au@SBA-15 and 3DOMM
      exhibit remarkable synergistic effects for accelerating direct electron transfer
      (DET) between HRP and the electrode. Under the optimal conditions, the DET
      current signal increased proportionally to CA 19-9 concentration in the range of
      0.05 to 15.65 U mL(-1) with a detection limit of 0.01 U mL(-1). Moreover, the
      immunosensor showed high selectivity, good stability, satisfactory
      reproducibility and regeneration. Importantly, the developed method was used to
      assay clinical serum specimens, achieving a good relation with those obtained
      from the commercialized electrochemiluminescent method.

PMID- 24560372
TI  - "Orange alert": a fluorescent detector for bisphenol A in water environments.
AB  - Due to the prevalent use of polycarbonate plastics and epoxy resins in packaging
      materials and paints for ships, there has been a widespread global contamination
      of environmental water sources with bisphenol A (BPA). BPA, an endocrine
      disruptor, has been found to cause tremendous health problems. Therefore, there
      is an urgent need for detecting BPA in a convenient and sensitive manner to
      ensure water safety. Herein, we develop a fluorescent turn-on BPA probe, named
      Bisphenol Orange (BPO), which could conveniently detect BPA in a wide variety of
      real water samples including sea water, drain water and drinking water. BPO shows
      superior selectivity toward BPA and up to 70-fold increase in fluorescence
      emission at 580 nm when mixed with BPA in water. Mechanistic studies suggest a
      plausible water-dependent formation of hydrophobic BPA clusters which favorably
      trap and restrict the rotation of BPO and recover its inherent fluorescence.

PMID- 24560373
TI  - Microgeographic adaptation and the spatial scale of evolution.
AB  - Local adaptation has been a major focus of evolutionary ecologists working across
      diverse systems for decades. However, little of this research has explored
      variation at microgeographic scales because it has often been assumed that high
      rates of gene flow will prevent adaptive divergence at fine spatial scales. Here,
      we establish a quantitative definition of microgeographic adaptation based on
      Wright's dispersal neighborhood that standardizes dispersal abilities, enabling
      this measure to be compared across species. We use this definition to evaluate
      growing evidence of evolutionary divergence at fine spatial scales. We identify
      the main mechanisms known to facilitate this adaptation and highlight
      illustrative examples of microgeographic evolution in nature. Collectively, this
      evidence requires that we revisit our understanding of the spatial scale of
      adaptation and consider how microgeographic adaptation and its driving mechanisms
      can fundamentally alter ecological and evolutionary dynamics in nature. 

PMID- 24560375
TI  - In memoriam of Professor Theodore L. Munsat (1930-2013): his outstanding legacy
      with the WFN.
AB  - The World Federation of Neurology (WFN) lost an outstanding leader on November
      22, 2013 with the death of Professor Theodore Leon Munsat ("Ted"), in Waltham,
      Massachusetts, USA. Professor Munsat was Emeritus professor of Neurology at Tufts
      University School of Medicine and served the WFN in several capacities as
      trustee, chairman of the WFN Education and research committees, chairman of the
      WFN ALS Research group and founding director of the WFN Seminars in Clinical
      Neurology. He was president of the American Academy of Neurology (AAN), 1989
      1991, chairman of the Continuing Educational Committee of the AAN and founding
      director of AAN's premier continuing medical education journal Continuum:
      Lifelong Learning in Neurology. He left an outstanding legacy with the WFN. 

PMID- 24560374
TI  - No evidence that runs of homozygosity are associated with schizophrenia in an
      Irish genome-wide association dataset.
AB  - Runs of homozygosity (ROH), regions of the genome containing many consecutive
      homozygous SNPs, may represent two copies of a haplotype inherited from a common
      ancestor. A rare variant on this haplotype could thus be present in a homozygous
      and potentially recessive state. To detect rare risk variants for schizophrenia,
      we performed an ROH analysis in a homogeneous Irish genome wide association study
      (GWAS) dataset consisting of 1606 cases and 1794 controls. There was no genome
      wide excess of ROH in cases compared to controls (p=0.7986). No consensus ROH at
      individual loci showed association with schizophrenia after genome-wide
      correction. 

PMID- 24560376
TI  - Plasma factor VIII in non-puerperal cerebral venous thrombosis: a prospective
      case-control study.
AB  - Elevated plasma factor VIII (FVIII) is increasingly recognized as an independent
      risk factor for thrombotic diseases. Our aim was to evaluate the association of
      increased plasma FVIII with cerebral venous thrombosis (CVT). Forty eight
      patients with non-puerperal, aseptic CVT were recruited for the study along with
      50 age- and gender-matched, healthy controls. Blood samples were collected 3
      months after the thrombotic event in patients. Plasma FVIII and fibrinogen levels
      were measured by a functional clot-based assay. Mean plasma FVIII was
      significantly higher in patients when compared to controls (235.40 +/- 94.5
      vs.121.2 +/- 28.3IU/dl, p<0.001). Absence of significant elevation of fibrinogen
      suggested that the increase in FVIII was not due to an acute phase reaction.
      Elevated FVIII (>170 IU/dl) was associated with >18-fold increase in the risk for
      non-puerperal CVT (adjusted OR: 18.754, 95% CI 10.2-203.0, p<0.001). Non-O blood
      groups were more prevalent in CVT patients. Mean FVIII levels were higher in
      subjects with non-O blood group as compared to those with O blood group (155.16
      +/- 46.05 vs. 129.09 +/- 40.06 IU/dl, p<0.001). Multivariate analysis with
      logistic regression showed that only elevated FVIII, and not blood group, was
      significantly associated with CVT. Our study demonstrates that elevated FVIII is
      an independent risk factor for non-puerperal CVT in an Indian population.

PMID- 24560377
TI  - To clamp or not to clamp the main renal artery: the debate continues.

PMID- 24560378
TI  - How does a biopsy of endoscopically normal terminal ileum contribute to the
      diagnosis? Which patients should undergo biopsy?
AB  - BACKGROUND: Terminal ileum endoscopy and biopsy are the diagnostic tools of
      diseases attacking the ileum. However, abnormal histological findings can be
      found in endoscopically normal terminal ileum. OBJECTIVE: This study was
      performed to evaluate the histopathological results of biopsies from
      endoscopically normal terminal ileum in order to determine pre-procedure clinical
      and laboratory factors predicting abnormal histopathological results, if any.
      METHODS: A total of 297 patients who underwent colonoscopy and terminal ileum
      biopsy and had normal terminal ileum or a few aphthous ulcers in the terminal
      ileum together with completely normal colon mucosa were included in the study.
      The patients were grouped into two arms as normal cases and cases with aphthous
      ulcers. Histopathological and pre-procedural laboratory results of patients were
      analyzed according to their indications. RESULTS: The terminal ileum was
      endoscopically normal in 200 patients, and 97 patients had aphthous ulcers.
      Chronic ileitis rate was present in 5.5% of those with endoscopically normal
      terminal ileum and in 39.2% of the patients with aphthous ulcers. In both groups,
      the highest rate of chronic ileitis was detected in the patients with known
      inflammatory bowel disease (IBD) (15.4 and 50%, respectively), anemia (9.5 and
      43.5%, respectively), and in the patients having chronic diarrhea together with
      abdominal pain (7.7 and 44.8%, respectively). We found that the sensitivity of
      mean platelet volume for predicting chronic ileitis was 87% and the specificity
      was 45% at a cut-off value lower than 9.35 fl. CONCLUSION: In anemia indication
      or chronic diarrhea together with abdominal pain, the frequency of aphthous
      ulcers detected by ileoscopy and the frequency of chronic ileitis detected
      histopathologically despite a normal-appearing ileum were elevated.

PMID- 24560379
TI  - The effect of GABAmimetics on the duration of immobility in the forced swim test
      in albino mice.
AB  - OBJECTIVES: Studies regarding the role of gamma aminobutyric acid (GABA) in
      depression are conflicting. Therefore, it was decided to examine the effect of
      different drugs that enhance the GABA system on the time of immobility induced by
      the forced swim test (FST). MATERIALS AND METHODS: Adult albino mice were divided
      into several groups of six animals. Each group received an intraperitoneal
      injection of either imipramine (10, 20, or 30 mg/kg), diazepam (0.5, 1, or 2
      mg/kg), vigabatrin (100, 200, or 300 mg/kg), zolpidem (2.5, 5, or 10 mg/kg), or
      alprazolam (1, 2.5, or 5 mg/kg). Control groups received the appropriate vehicle.
      One hour after injection, the duration of immobility was measured for 5 min in
      the FST. The percentage change in the duration of immobility from the control was
      calculated for each group. The statistical test of the difference between the
      treated and the control groups was calculated using unpaired Student's t-test.
      RESULTS: Imipramine produced a significant dose-dependent decrease in the
      duration of immobility (78, 74, and 56%, respectively). Different doses of
      diazepam, vigabatrin, and zolpidem produced a significant increase in the
      duration of immobility (119, 126, and 128%), (116, 124, and 128%), and (108, 109,
      and 119%), respectively. The two low doses of alprazolam produced a significant
      increase (115 and 120%), while the high dose produced a significant decrease in
      the duration of immobility (74%). CONCLUSION: Increasing central GABAergic
      activity by different mechanisms has resulted in a depressant-like activity
      measured as an increase in the duration of immobility in the FST model of
      depression.

PMID- 24560380
TI  - Burnout among physicians.
AB  - Burnout is a common syndrome seen in healthcare workers, particularly physicians
      who are exposed to a high level of stress at work; it includes emotional
      exhaustion, depersonalization, and low personal accomplishment. Burnout among
      physicians has garnered significant attention because of the negative impact it
      renders on patient care and medical personnel. Physicians who had high burnout
      levels reportedly committed more medical errors. Stress management programs that
      range from relaxation to cognitive-behavioral and patient-centered therapy have
      been found to be of utmost significance when it comes to preventing and treating
      burnout. However, evidence is insufficient to support that stress management
      programs can help reducing job-related stress beyond the intervention period, and
      similarly mindfulness-based stress reduction interventions efficiently reduce
      psychological distress and negative vibes, and encourage empathy while
      significantly enhancing physicians' quality of life. On the other hand, a few
      small studies have suggested that Balint sessions can have a promising positive
      effect in preventing burnout; moreover exercises can reduce anxiety levels and
      exhaustion symptoms while improving the mental and physical well-being of
      healthcare workers. Occupational interventions in the work settings can also
      improve the emotional and work-induced exhaustion. Combining both individual and
      organizational interventions can have a good impact in reducing burnout scores
      among physicians; therefore, multidisciplinary actions that include changes in
      the work environmental factors along with stress management programs that teach
      people how to cope better with stressful events showed promising solutions to
      manage burnout. However, until now there have been no rigorous studies to prove
      this. More interventional research targeting medical students, residents, and
      practicing physicians are needed in order to improve psychological well-being,
      professional careers, as well as the quality of care provided to patients. 

PMID- 24560382
TI  - Combat exposure and migraine headache: evidence from exogenous deployment
      assignment.
AB  - Migraine headache is a growing problem for U.S. servicemembers deployed to Iraq
      and Afghanistan and has been linked to substantial negative socioeconomic
      consequences. However, there has been no comprehensive examination of the
      relationship between combat exposure and migraine headache or its stress-related
      triggers. Analyzing data drawn from the National Longitudinal Study of Adolescent
      Health, we use exogenous variation in deployment assignment to estimate the
      effect of combat exposure on migraine headache. We find that those deployed to a
      combat zone with enemy firefight are at substantially increased risk for migraine
      headache relative to those deployed to non-combat zones outside the United States
      or to combat zones without enemy firefight. We find that combat-induced sleep
      disorders, stress-related psychological problems, and physical injuries in combat
      explain approximately 40-45 percent of the relationship between combat exposure
      and migraine headache. 

PMID- 24560381
TI  - Cetuximab-induced esophageal ulcer: the first report in literature.

PMID- 24560383
TI  - Towards sustainable safe drinking water supply in low- and middle-income
      countries: the challenges of geogenic contaminants and mitigation measures.

PMID- 24560385
TI  - Severe hyperkalemia with refractory ventricular fibrillation: successful
      resuscitation using extracorporeal membrane oxygenation.

PMID- 24560384
TI  - A conceptual model of emergency physician decision making for head computed
      tomography in mild head injury.
AB  - The use of computed tomographic scanning in blunt head trauma has increased
      dramatically in recent years without an accompanying rise in the prevalence of
      injury or hospital admission for serious conditions. Because computed tomography
      is neither harmless nor inexpensive, researchers have attempted to optimize
      utilization, largely through research that describes which clinical variables
      predict intracranial injury, and use this information to develop clinical
      decision instruments. Although such techniques may be useful when the benefits
      and harms of each strategy (neuroimaging vs observation) are quantifiable and
      amenable to comparison, the exact magnitude of these benefits and harms remains
      unknown in this clinical scenario. We believe that most clinical decision
      instrument development efforts are misguided insofar as they ignore critical,
      nonclinical factors influencing the decision to image. In this article, we
      propose a conceptual model to illustrate how clinical and nonclinical factors
      influence emergency physicians making this decision. We posit that elements
      unrelated to standard clinical factors, such as personality of the physician,
      fear of litigation and of missed diagnoses, patient expectations, and
      compensation method, may have equal or greater impact on actual decision making
      than traditional clinical factors. We believe that 3 particular factors deserve
      special consideration for further research: fear of error/malpractice, financial
      incentives, and patient engagement. Acknowledgement and study of these factors
      will be essential if we are to understand how emergency physicians truly make
      these decisions and how test-ordering behavior can be modified. 

PMID- 24560386
TI  - The author's reply.

PMID- 24560387
TI  - Cerebrospinal fluid/blood glucose should be used as a good diagnostic tool and
      mortality indicator in bacterial meningitis.

PMID- 24560388
TI  - Determining the etiology of hypotension: associated with reperfusion injury?

PMID- 24560389
TI  - Does ultrasonographic lung sliding sign always verify the success in endotracheal
      tube intubation?

PMID- 24560390
TI  - The pelvic digit anomaly in a patient with multiple fractures: does it mimic the
      fracture?

PMID- 24560391
TI  - Clopidogrel resistance in diabetic patient with acute myocardial infarction due
      to stent thrombosis.
AB  - Stent thrombosis is a morbid complication after percutaneous coronary
      intervention. Dual antiplatelet therapy significantly reduces stent thrombosis
      risk and forms currently the basis in acute ST elevation myocardial infarction
      pharmacologic treatment. The introduction of clopidogrel has made a major advance
      in the acute coronary syndrome treatment. However, there is growing evidence
      about failure in antiplatelet response after clopidogrel, which may lead to
      subsequent risk of future thrombotic events. The antiplatelet inhibitory effect
      of clopidogrel varies widely among individuals. High on-treatment platelet
      reactivity has been repeatedly associated with a hazard for cardiovascular
      events, including stent thrombosis. Laboratory monitoring of antiplatelet therapy
      efficacy may help identify patients with insufficient antiplatelet response.
      Prasugrel therapy was repeatedly described as an effective method to overcome
      clopidogrel resistance. We report a case of diabetic patient in whom myocardial
      reinfarction due to stent thrombosis developed. Clopidogrel resistance was
      detected in this patient using light transmission aggregometry and vasodilator
      stimulated phosphoprotein phosphorylation assessment. After prasugrel
      administration, no other ischemic event occurred, and patient was released to
      outpatient care in good general condition. 

PMID- 24560392
TI  - The comparison of heparinized insulin syringes and safety-engineered blood gas
      syringes used in arterial blood gas sampling in the ED setting (randomized
      controlled study).
AB  - INTRODUCTION: The arterial blood gas measurement process is a painful and
      invasive procedure, often uncomfortable for both the patient and the physician.
      Because the patient-related factors that determine the difficulty of the process
      cannot be controlled, the physician-related factors and blood gas measurement
      techniques are a modifiable area of improvement that ought to be considered. Many
      hospitals use insulin syringes or syringes washed with heparin for the purpose of
      blood gas measurement because they do not have blood gas-specific syringes. In
      this prospective cross-sectional study, we aimed to compare safety-engineered
      blood gas syringes and conventional heparinized syringes used during the arterial
      blood gas extraction process in terms of ease of operation, the physician-patient
      satisfaction, laboratory appropriateness, and complications. METHODS: Our study
      included patients whose arterial blood gas needed to be measured in the emergency
      department and who agreed to participate in the study. Patients were randomly
      divided into 2 groups. The arterial blood gas of the patients from the first
      group was measured by using conventional heparinized syringes, whereas safety
      engineered blood gas syringes were used to measure the arterial blood gas of the
      patients from the second group. The groups were compared in terms of demographic
      data, the number of attempts, the physician and patient satisfaction, early and
      late-term complications, and laboratory appropriateness of the taken sample.
      RESULTS: A total of 550 patients were included in our study in a 2-month study
      period. There were no significant differences between patients in terms of sex,
      age, weight, height, body mass index, and wrist circumference. In addition, the
      number of attempts (P=.489), patients' pain level during the procedure (P=.145),
      and the degree of difficulty of the procedure according to the patient (P=.109)
      and physician (P=.554) were not significantly different between the groups. After
      arterial blood gas extraction procedure, 115 patients (20.9%) developed
      complications. In the conventional heparinized syringe group, the complication
      rate (n=69; 25.1%) was significantly higher compared with the group that used
      safety-engineered blood gas syringes (n=46; 16%; P=.0211). Localized pain, which
      is one of the most common early complications, was more frequent in the
      conventional heparinized syringe group (19.3%). Complications in women (P=.003)
      and local pain (P=.01) developed lesser in the second group that used safety
      engineered blood gas syringes, and the patient-physician satisfaction was higher
      in that group, as well. In the evaluation 48 hours after the procedure, the
      ratios of infection and local hematoma were higher in the conventional
      heparinized syringe group (P=.0213 and P < .0001). CONCLUSION: In this study, we
      did not find any significant differences between the conventional heparinized
      syringes and safety-engineered blood gas syringes in terms of ease of operation,
      physician and patient satisfaction, and appropriateness of the taken sample.
      However, patients whose arterial blood gas was extracted by using safety
      engineered blood gas syringes felt less pain and experienced fewer infections and
      hematomas at their puncture site.

PMID- 24560393
TI  - An unusual cause of acute abdominal pain in dengue fever.
AB  - Dengue fever is an acute febrile viral disease caused by the bite of Aedes
      aegypti mosquito. It is a major health problem especially in tropical and
      subtropical areas including South East Asia and Pakistan. In the past few years,
      dengue fever has been endemic in Northern Punjab. Physicians managing dengue
      fever come across varied and uncommon complications of dengue fever. We report a
      case of dengue fever that developed severe right upper quadrant abdominal pain
      and induration after extreme retching and vomiting for 2 days. A rectus sheath
      hematoma was confirmed on noncontrast computed tomography (CT). Rectus sheath
      hematoma as a complication of dengue fever has rarely been reported before and
      never from this part of the world. Rectus sheath hematoma is an uncommon and
      often clinically misdiagnosed cause of abdominal pain. It is the result of
      bleeding into the rectus sheath from damage to the superior or inferior
      epigastric artery or their branches or from a direct tear of the rectus muscle.
      It can mimic almost any abdominal condition (See Fig.) (See Table).

PMID- 24560394
TI  - Validation of a prediction rule for endocarditis in febrile injection drug users.
AB  - BACKGROUND: Infectious endocarditis (IE) in febrile injection drug users (IDUs)
      is a critical diagnosis to identify in the emergency department (ED). A decision
      tool that identifies patients at very low risk for endocarditis using readily
      available clinical data could reduce admissions and cost. OBJECTIVE: To evaluate
      the diagnostic performance of a previously derived decision instrument to rule
      out endocarditis in febrile IDUs (Prediction Rule for Endocarditis in Injection
      Drug Users [PRE-IDU]) and to develop a prediction model for likelihood of
      endocarditis for those who are not ruled out by PRE-IDU. METHODS: Febrile IDUs
      admitted to rule out endocarditis were prospectively enrolled from 2 urban EDs in
      June 2007 to March 2011. Clinical data from ED presentation (first 6 hours) and
      outcome data from inpatient records were recorded and reviewed by 2 independent
      investigators. Diagnosis of IE was based on modified Duke criteria and discharge
      summaries. The diagnostic performance of PRE-IDU, which combines tachycardia,
      cardiac murmur, and absence of skin infection, was determined using recursive
      partitioning and logistic regression modeling. RESULTS: Of the 249 subjects, 18
      (7%) had IE. Recursive partitioning yielded an instrument with 100% sensitivity
      (95% confidence interval [CI], 84%-100%) and 100% negative predictive value (95%
      CI, 91%-100%), but low specificity (13%; 95% CI, 12%-13%). Multiple logistic
      regression modeling with the 3 clinical predictors allowed risk stratification
      with posttest probabilities ranging from 3% to 20%. CONCLUSION: The PRE-IDU
      instrument predicted IE with high sensitivity and ruled out IE with high negative
      predictive value. Our logistic regression model provided posttest probabilities
      ranging from 3% to 20%. The PRE-IDU instrument and the associated model may help
      guide hospital admission and diagnostic testing in evaluation of febrile IDUs in
      the ED.

PMID- 24560395
TI  - Comparison of 3 scoring systems to predict mortality from unstable upper
      gastrointestinal bleeding in cirrhotic patients.
AB  - OBJECTIVE: We aimed to compare the performance of Glasgow-Blatchford,
      preendoscopic Rockall, and model for end-stage liver disease (MELD) scores in
      cirrhotic patients with unstable upper gastrointestinal bleeding (UGIB) in the
      emergency department (ED). METHODS: This was a retrospective cohort study
      conducted at a university-affiliated teaching hospital. Adult cirrhotic patients
      who presented with acute UGIB and unstable vital signs (heart rate >100 beats/min
      or systolic blood pressure <100 mm Hg) between January 2009 and February 2011
      were included. Patients who were transferred from another hospital, received no
      emergency endoscopy study, or had incomplete medical records were excluded. Data
      were retrieved from the admission list of the ED critical zone using
      international classification of disease code via computer registration. RESULTS:
      Among enrolled visits, the initial median hemoglobin level was 8.6 (interquartile
      range, 7.2-10.1) mg/dL in the ED. The median heart rate and systolic blood
      pressure were 111.0 beats/min and 94.0 mm Hg, respectively. The endoscopic
      diagnosis of variceal bleeding accounted for 86.6% of the events. The mortality
      rate was 16.0% (19/119). Model for end-stage liver disease score performed better
      with an area under the curve (AUC) of 0.736 (95% confidence interval [CI], 0.629
      0.842; P = .001) compared with other scoring systems (Glasgow-Blatchford score:
      AUC, 0.527; 95% CI, 0.393-0.661; P = .709; preendoscopic Rockall score: AUC,
      0.591; 95% CI, 0.465-0.717; P = .208). CONCLUSION: Model for end-stage liver
      disease score performed better in terms of predicting mortality of unstable UGIB
      in cirrhotic patients compared with Glasgow-Blatchford and preendoscopic Rockall
      scores in the ED.

PMID- 24560396
TI  - Unusual presenting of acute aortic dissection due to penetrating atheromatous
      ulcer.
AB  - Penetrating atheromatous ulcer (PAU) is an atherosclerotic ulcer penetrating the
      internal elastic lamina of the aortic wall causing a hematoma within the media
      layer of aorta. They are commonly located in the descending aorta of the elderly
      and hypertensive patients. They may rarely be complicated by aortic dissection.
      We report a relative young normotensive patient presenting with acute aortic
      dissection due to PAU located in the ascending aorta.

PMID- 24560397
TI  - Recurrent bottlenecks in the malaria life cycle obscure signals of positive
      selection.
AB  - Detecting signals of selection in the genome of malaria parasites is a key to
      identify targets for drug and vaccine development. Malaria parasites have a
      unique life cycle alternating between vector and host organism with a population
      bottleneck at each transition. These recurrent bottlenecks could influence the
      patterns of genetic diversity and the power of existing population genetic tools
      to identify sites under positive selection. We therefore simulated the site
      frequency spectrum of a beneficial mutant allele through time under the malaria
      life cycle. We investigated the power of current population genetic methods to
      detect positive selection based on the site-frequency spectrum as well as
      temporal changes in allele frequency. We found that a within-host selective
      advantage is difficult to detect using these methods. Although a between-host
      transmission advantage could be detected, the power is decreased when compared
      with the classical Wright-Fisher (WF) population model. Using an adjusted null
      site-frequency spectrum that takes the malaria life cycle into account, the power
      of tests based on the site-frequency spectrum to detect positive selection is
      greatly improved. Our study demonstrates the importance of considering the life
      cycle in genetic analysis, especially in parasites with complex life cycles.

PMID- 24560398
TI  - Anti-thyroglobulin antibodies in differentiated thyroid carcinoma patients: Study
      of the clinical and biological parameters.
AB  - OBJECTIVES: Detection of thyroglobulin in serum is of major clinical importance.
      The current assay techniques do not have all the qualifications which make the
      results of thyroglobulin difficult to interpret. The major problem is the
      autoantibody thyroglobulin (TgAb) interference. They induce an underestimation of
      thyroglobulin concentrations in the immunometric methods. We report in this study
      the clinical and biological parameters of anti-thyroglobulin antibodies of
      patients with differentiated thyroid carcinoma. PATIENTS AND METHODS: A total of
      246 patients with thyroid carcinomas were delicately selected from 2005 to 2012
      in the nuclear medicine service of Tlemcen University hospital. Plasma thyroid
      stimulating hormone, thyroglobulin and anti-thyroglobulin antibodies were
      measured on Elecsys with the standardised Immunoradiometric assay. RESULTS: We
      noticed that there is a rapid increase in the annual number of cases of thyroid
      carcinoma detected since 2007 with a much higher incidence in women. The rate of
      anti-thyroglobulin antibody interference reached 20.40%. The distribution of
      positive anti-thyroglobulin antibodies is not related to age or sex. CONCLUSION:
      It is recommended to systematically measure anti-thyroglobulin antibodies, in
      parallel with the determination of thyroglobulin, using a sensitive method.

PMID- 24560399
TI  - Insufficiency of electrocardiogram alone in predicting infrahisian abnormalities
      in patients with type 1 myotonic dystrophy.

PMID- 24560400
TI  - Cardiac surgery in indigenous Australians: early onset cardiac disease with
      follow-up challenges.
AB  - OBJECTIVE: To review the risk factors, complications and follow-up of Indigenous
      patients post cardiac surgery. METHODS: This was a retrospective study of
      Indigenous patients who underwent cardiac surgery at an Australian tertiary
      hospital between 2002 and 2009. Patients' medical notes were reviewed and data
      collected and analysed. RESULTS: There were 220 Indigenous patients who had
      cardiac surgery. Non-elective surgery was performed in 45.0% (99/220). A history
      of smoking was reported by 76.8% (169/220). The most common operation was
      coronary artery bypass grafting with a mean age of 55 years. Of the 71 valve
      operations, 31.0% had rheumatic heart disease. Mechanical valves were given to
      56.3% (40/71) of patients with a mean age of 45 years. The rate of peri-operative
      bleeding requiring blood transfusion or reoperation was 8.6% (19/220) and 28-day
      mortality was 0.45% (1/220). Of the patients with mechanical valves, 10.0% (4/40)
      did not present for outpatient review. Late anticoagulation related complications
      were haemorrhagic stroke 7.5% (3/40) and ischaemic bowel 2.5% (1/40). Late
      mortality was 9.5% (21/220). Late anticoagulation related deaths were in 1.8%
      (4/220), of whom 0.9% (2/220) had mechanical valves. CONCLUSIONS: The mean age of
      52 years at which Indigenous patients have cardiac surgery is significantly low
      compared to non-Indigenous patients. Indigenous patients have multiple risk
      factors for cardiac disease and with a large number requiring emergency surgery.
      Although surgical outcome in the short term is favourable, a large number of
      patients are lost to follow-up. The use of mechanical valve and warfarin should
      be individualised. Strategic post-operative follow-up mechanisms are needed to
      address these issues.

PMID- 24560401
TI  - Improving the quality of percutaneous revascularisation in patients with
      multivessel disease in Australia: cost-effectiveness, public health implications,
      and budget impact of FFR-guided PCI.
AB  - PURPOSE: The international multicentre FAME Study (n=1,005) demonstrated
      significant health benefits for patients undergoing multivessel percutaneous
      coronary intervention (PCI) guided by fractional flow reserve (FFR) measurement
      compared with angiography guidance alone (ANGIO). We determined the cost
      effectiveness and the public health/budget impact for Australia. METHODS: We
      performed a prospective economic evaluation comparing FFR vs. ANGIO in patients
      with multivessel disease based on original patient-level FAME data. We used
      Australian utilities (EQ-5D) and costs to calculate quality-adjusted life years
      (QALYs) and incremental cost-effectiveness adopting the societal perspective. The
      public health and budget impact from the payer's perspective was based on
      Australian PCI registries. Uncertainty was explored using deterministic
      sensitivity analyses and the bootstrap method (n=5,000 samples). RESULTS: The
      cost-effectiveness analysis showed that FFR was cost-saving and reduces costs by
      1,776 AUD per patient during one year. Over a two-year time horizon, the public
      health impact ranged from 7.8 to 73.9 QALYs gained and the budget impact from 1.8
      to 14.5 million AUD total cost savings. Sensitivity analyses demonstrated that
      FFR was cost-saving over a wide range of assumptions. CONCLUSIONS: FFR-guided PCI
      in patients with multivessel coronary disease substantially reduces cardiac
      events, improves QALYs and is cost-saving in the Australian health care system.

PMID- 24560402
TI  - Elevated hyaluronan levels in patients with rheumatic mitral stenosis and
      pulmonary arterial thromboembolism.
AB  - INTRODUCTION: The role of hyaluronan (HA) was previously demonstrated in patients
      with idiopathic pulmonary arterial hypertension (PAH). Mitral stenosis (MS) and
      pulmonary arterial thromboembolism (PTE) are important health problems that can
      cause pulmonovascular pathology. Pulmonary arterial hypertension develops
      especially in untreated patients with severe MS and most of patients with PTE.
      However, there is no data about HA levels in patients with MS and PTE. In this
      study, we investigated HA levels in patients with rheumatic MS and PTE. METHOD:
      Study population was divided into three groups. MS group consisted of 18 patients
      with moderate or severe MS. PTE group consisted of 16 patients with PTE. Control
      group consisted of 15 subjects without cardiac and pulmonary disease.
      Percutaneous mitral balloon valvuloplasty (PMV) was performed on all patients in
      MS group. Mitral gradients and systolic pulmonary arterial pressure (sPAP) were
      measured in all patients. HA levels were measured at baseline and first month
      after PMV. RESULTS: Mean sPAP+/-SD (mmHg) was 23+/-3 in the control group, 44+/-9
      in the MS group and 66+/-11 in the PTE group (p<0.001). Baseline serum HA levels
      were significantly correlated with sPAP(echo) (r=0.332 p=0.03) and sPAP(cath)
      (r=0.559, p=0.007). Serum HA levels (ng/ml) in MS were significantly higher
      compared to controls [39+/-14 vs 24+/-11; p=0.01]. Patients in PTE group had the
      highest HA levels (61+/-21; p<0.001). Serum HA levels were significantly
      decreased at the first month after PMV in patients with MS [MS group: 39+/-14
      (ng/ml), after PMV: 31+/-8; p=0.03]. CONCLUSION: This is the first article
      showing that both MS and PTE can cause increased serum HA levels. HA levels were
      decreased with PMV procedure in patients with MS.

PMID- 24560403
TI  - Emerging roles of MCPH1: expedition from primary microcephaly to cancer.
AB  - Genetic mutations in microcephalin1 (MCPH1) cause primary autosomal recessive
      microcephaly which is characterized by a marked reduction in brain size. MCPH1
      encodes a centrosomal protein with three BRCT (BRCA1 C-terminal) domains. Also,
      it is a key regulator of DNA repair pathway and cell cycle checkpoints.
      Interestingly, in the past few years, many research studies have explored the
      role of MCPH1, a neurodevelopmental gene in several cancers and its tumor
      suppressor functions have been elucidated. Given the diverse new emerging roles,
      it becomes critical to review and summarize the multiple roles of MCPH1 that is
      currently lacking in the literature. In this review after systematic analysis of
      literature, we summarise the multiple functional roles of MCPH1 in centrosomal,
      DNA repair and apoptotic pathways. Additionally, we discuss the considerable
      efforts taken to understand the implications of MCPH1 in diseases such as primary
      microcephaly and its other emerging association with cancer and otitis media. The
      promising view is that MCPH1 has distinct roles and its clinical associations in
      various diseases makes it an attractive therapeutic target. 

PMID- 24560404
TI  - Cyclooxygenase-2 expression is associated with vascular endothelial growth factor
      c and lymph node metastasis in human oral tongue cancer.
AB  - OBJECTIVE: This study aimed to determine the relationship of cyclooxygenase-2
      (COX-2) and vascular endothelial growth factor-c (VEGF-C) expression with
      lymphangiogenesis, lymph node metastasis (LNM), and other clinicopathologic
      features in human oral tongue cancers. STUDY DESIGN: Forty tongue cancer
      specimens were immunohistochemically examined for COX-2 and VEGF-C expression and
      for lymphatic vessel density (LVD). We analyzed the relationships between COX-2
      and VEGF-C expression and the relationships of such expression with
      clinicopathologic findings and survival of patients. RESULTS: Eighteen tumors out
      of 40 (45%) showed COX-2 expression, and 18 tumors (45%) expressed VEGF-C. Twelve
      tumors (30%) coexpressed COX-2/VEGF-C. A significant correlation was found
      between COX-2 and VEGF-C expression (P < .01). Of note, COX-2/VEGF-C coexpression
      significantly correlated with lymphangiogenesis, LNM, TNM stage (P < .01), and
      LVD (P < .05). In Cox regression for survival, COX-2/VEGF-C coexpression was
      identified as an independent prognostic factor (P < .05). CONCLUSIONS: Our
      results suggest that examination of immunohistochemical expression of COX-2 and
      VEGF-C predicts LNM and survival in human oral tongue cancers.

PMID- 24560406
TI  - Oral presentation of 10 patients with Cowden syndrome.
AB  - Cowden syndrome (CS) is an autosomal dominant genodermatosis that frequently
      affects several tissues with hamartomatous growth. The oral cavity is quite
      commonly involved with papillomatous lesions, which can be crucial to early
      diagnosis of this disease. In this series, 10 patients with a great diversity of
      manifestations associated with CS are presented, in whom oral papillomatosis was
      a constant and relevant finding to establish the diagnosis of CS. The role of the
      dentist in recognizing the oral lesions, the other diagnostic criteria, the risk
      for the development of malignancies, and the importance of lifetime follow-up are
      discussed. 

PMID- 24560405
TI  - Life-threatening oronasal hemorrhage managed by transcatheter embolization of
      bilateral maxillary arteries in an elderly patient with comminuted LeFort I
      fracture.
AB  - Massive orofacial hemorrhage mostly occurs in younger individuals unilaterally
      and is associated with extensive LeFort fractures. Here we describe a 91-year-old
      man who sustained a life-threatening hemorrhage of the bilateral internal
      maxillary artery (IMA) system with a comminuted LeFort I fracture caused by a
      road traffic accident while he was driving. His injury severity score was high
      (34), but no severe brain injury was sustained. Transarterial embolization (TAE)
      was performed to control the intractable hemorrhage. The patient survived and has
      an acceptable outcome. Although rare, this case may be representative of a trend
      in maxillofacial injuries in the elderly resulting from worldwide motorization
      and steady aging of more active populations. Life-threatening hemorrhage of the
      bilateral IMA system occurs even in LeFort I fractures. Controlling an
      intractable oronasal hemorrhage with TAE would lead to survival with less severe
      morbidity, even for the very elderly with no severe brain injuries.

PMID- 24560407
TI  - Characteristics of hospitalizations attributed to herpetic gingivostomatitis:
      analysis of nationwide inpatient sample.
AB  - OBJECTIVE: Herpetic gingivostomatitis (HGS) is a prevalent oral condition of
      viral origin. Some patients with HGS visit emergency departments for treatment.
      This study is aimed at determining the nationwide estimates of hospitalizations
      due to HGS in the United States. STUDY DESIGN: The Nationwide Inpatient Sample of
      the Agency for Healthcare Research and Quality was used for the years 2004 to
      2010. Hospital admissions with a primary diagnosis of HGS were identified using
      International Classification of Diseases (ICD)-9-CM code 054.2. RESULTS: During
      the study period, a total of 12 536 hospitalizations were attributed to HGS, and
      the number of hospitalizations per year (mean, 1791) remained fairly constant
      during the years examined. The median age was 3.2 years. The mean age (15.6 years
      for the overall period) ranged from a low of 15.2 in 2010 to a high of 16.8 in
      2007. The total charges that resulted from these hospitalizations were $229.4
      million. CONCLUSIONS: This study further confirms that substantial resources are
      spent in treating oral conditions in hospital settings.

PMID- 24560408
TI  - Factors associated with comorbidity patterns in full and partial PTSD: findings
      from the PsyCoLaus study.
AB  - Subtypes of comorbid conditions and their associated trauma and clinical
      characteristics in full and partial PTSD were examined. Data from 289 subjects
      from the general population that met criteria for full or partial PTSD were
      analyzed. Latent class analyses (LCA) were performed to derive homogeneous
      patterns of DSM-IV Axis-I disorders and anti-social personality comorbid to PTSD.
      Logistic regression models were conducted to characterize these classes by trauma
      related and clinical features. The LCA revealed three classes: (1) low
      comorbidity; (2) high comorbidity with primarily substance-related disorders and
      a higher proportion of males; and (3) more severe PTSD-symptomatology and higher
      comorbid anxiety disorders and depression, almost entirely represented by
      females. Exposure to sexual abuse was more likely in the substance-dependent
      class and contributed strongly to the distinction between classes. Affective
      disorders tended to precede the onset of PTSD in the substance-dependent class,
      whereas phobias were more likely to follow PTSD in the depressed-anxious class.
      Posttrauma onset of alcohol use disorders in the substance dependent class
      confirmed the self-medication hypothesis. The three classes of comorbidity and
      their sequence of onset with PTSD suggest different mechanisms involved in their
      development. Our findings suggest that PTSD-related comorbidity subtypes also
      apply to individuals with partial PTSD. 

PMID- 24560409
TI  - A new case of Job's syndrome at the clinic: a diagnostic challenge.
AB  - Job's syndrome or Hyperimmunoglobulin E syndrome (HIES) is a rare primary
      immunodeficiency characterized by recurrent soft tissue infections, coarse face,
      skeletal and vascular abnormalities, and markedly high levels of Immunoglobulin
      E. Eczema that resembles atopic dermatitis but is refractory to traditional
      treatment and severe and recurrent bacterial pneumonias often recognized during
      childhood. Early diagnosis and treatment prevent progressive pulmonary sequellae
      and increase survival. About 200 cases of HIES has been reported worldwide. The
      authors report a new case of HIES with one of the worst pulmonary sequellae found
      in the literature on this subject and review this infrequent topic. 

PMID- 24560410
TI  - Smoking cessation effectiveness in smokers with COPD and asthma under real life
      conditions.
AB  - INTRODUCTION: Although smoking cessation is strongly indicated by international
      guidelines as an effective therapeutic tool for patients with COPD and Asthma, a
      large proportion of them do not quit smoking and they are regarded as a
      "difficult" target group. AIM: To study the effectiveness of an intensive smoking
      cessation program in smokers with COPD and asthma under real-life conditions.
      METHODS: 166 smokers with COPD, 120 smokers with asthma and 1854 control smokers
      attended the smoking cessation program in the out-patient patient Smoking
      Cessation Clinic of the Pulmonary Department in Athens University. Continuous
      Abstinence Rate (CAR) was evaluated in 3, 6, 9 and 12 months after the target
      quit date. RESULTS: Short-term CAR (in 3 months) was 49.4% for COPD smokers,
      51.7% for asthmatic smokers and 48.0% for the control group of smokers. 12 months
      after the initial visit the CAR was 13.9%, 18.3% and 15.9%, respectively. No
      statistically significant differences between groups at any study period were
      found. Smokers with good compliance with the program had higher long-term CAR
      after 12 months: 37.7% in COPD smokers, 40.0% in asthmatic smokers and 39.3% in
      control smokers. High CAR was observed at all stages of COPD severity.
      CONCLUSION: The results support the view that smokers with respiratory
      obstructive airway diseases of any severity should be offered an intensive
      smoking cessation program with regular and long-term follow-up. This will help
      them to achieve high abstinence rates and prevent relapses.

PMID- 24560411
TI  - The nuclear factor I/A (NFIA) gene is associated with the asthma plus rhinitis
      phenotype.
AB  - BACKGROUND: A previous genome-wide linkage scan in 295 families of the French
      Epidemiological Study on the Genetics and Environment of Asthma (EGEA) showed
      strong evidence of linkage of the 1p31 region to the combined asthma plus
      allergic rhinitis (AR) phenotype. OBJECTIVE: Our purpose was to conduct fine
      scale mapping of the 1p31 linkage region to identify the genetic variants
      associated with asthma plus AR. METHODS: Association analyses with the asthma
      plus rhinitis phenotype were first conducted in the EGEA family sample using the
      family-based association method (FBAT) and logistic regression. The test of
      homogeneity of association between asthma plus AR versus asthma alone or AR alone
      was also applied. Replication of EGEA findings was sought in French-Canadian and
      United Kingdom family samples. RESULTS: We found a significant association
      between asthma plus rhinitis and a 1p31 genetic variant (P = 2 * 10(-5) for
      rs12122228, which reached the multiple testing-corrected threshold) in EGEA using
      FBAT. There was evidence of heterogeneity of association between asthma plus AR
      versus asthma alone or AR alone (P = .03). A Meta-analysis of FBAT results from
      EGEA and French-Canadian families improved evidence for both association and
      heterogeneity (P = 5 * 10(-6) and P = .008, respectively), whereas a meta
      analysis of EGEA, French-Canadian, and United Kingdom samples based on logistic
      regression slightly increased the evidence for heterogeneity. CONCLUSION: The
      single nucleotide polymorphism specifically associated to asthma plus rhinitis is
      located in the flanking 5' untranslated region of the nuclear factor I/A (NFIA)
      gene, a strong candidate gene for asthma and AR.

PMID- 24560413
TI  - Associative and temporal learning: new directions.
AB  - Associative and temporal learning are fundamental properties of behavior. Despite
      the temporal dynamics of behavior, traditional associative (trial based)
      approaches have often ignored (within trial) timing properties of behavior.
      Therefore, associative and temporal learning are considered different, parallel
      strategies, whose mechanisms and rules are domain-specific. The rift between the
      two fields is not surprising considering the difference in questions, measures,
      and approaches. Some questions explored in this mini-review are as follows: Are
      the behavioral phenomena appropriately described, measured or quantified? How do
      animals integrate associative and temporal information? What are the behavioral
      processes that bridge the associative and temporal fields? How are associative
      and temporal information instantiated and processed in the brain? A resolution
      involves finding a more adept way (e.g., computational or biological) to describe
      the associative and temporal phenomena, for example by transforming them in a
      more abstract dimension, such as information (e.g., entropy calculation) or
      frequency (e.g., neural firing). When seen from this neural-computation vantage
      point, the distinctions between associative and temporal learning vanish, and the
      question becomes: What are the mechanisms that coexist, cooperate and compete in
      a brain that processes associative and temporal information in real time? This
      article is part of a Special Issue entitled: Associative and Temporal Learning. 

PMID- 24560414
TI  - Applying different equations to evaluate the level of mismatch between students
      and school furniture.
AB  - The mismatch between students and school furniture is likely to result in a
      number of negative effects, such as uncomfortable body posture, pain, and
      ultimately, it may also affect the learning process. This study's main aim is to
      review the literature describing the criteria equations for defining the mismatch
      between students and school furniture, to apply these equations to a specific
      sample and, based on the results, to propose a methodology to evaluate school
      furniture suitability. The literature review comprises one publications database,
      which was used to identify the studies carried out in the field of the
      abovementioned mismatch. The sample used for testing the different equations was
      composed of 2261 volunteer subjects from 14 schools. Fifteen studies were found
      to meet the criteria of this review and 21 equations to test 6 furniture
      dimensions were identified. Regarding seat height, there are considerable
      differences between the two most frequently used equations. Although seat to desk
      clearance was evaluated by knee height, this condition seems to be based on the
      false assumption that students are sitting on a chair with a proper seat height.
      Finally, the proposed methodology for suitability evaluation of school furniture
      should allow for a more reliable analysis of school furniture. 

PMID- 24560412
TI  - Exposure to food allergens through inflamed skin promotes intestinal food allergy
      through the thymic stromal lymphopoietin-basophil axis.
AB  - BACKGROUND: Exposure to food allergens through a disrupted skin barrier has been
      recognized as a potential factor in the increasing prevalence of food allergy.
      OBJECTIVE: We sought to test the immunologic mechanisms by which epicutaneous
      sensitization to food allergens predisposes to intestinal food allergy. METHODS:
      Mice were epicutaneously sensitized with ovalbumin or peanut on an atopic
      dermatitis-like skin lesion, followed by intragastric antigen challenge. Antigen
      specific serum IgE levels and T(H)2 cytokine responses were measured by ELISA.
      Expression of type 2 cytokines and mast cell proteases in the intestine were
      measured by using real-time PCR. Accumulation of basophils in the skin and mast
      cells in the intestine was examined by using flow cytometry. In vivo basophil
      depletion was achieved by using diphtheria toxin treatment of Baso-DTR mice. For
      cell-transfer studies, the basophil population was expanded in vivo by means of
      hydrodynamic tail vein injection of thymic stromal lymphopoietin (TSLP) cDNA
      plasmid. RESULTS: Sensitization to food allergens through an atopic dermatitis
      like skin lesion is associated with an expansion of TSLP-elicited basophils in
      the skin that promote antigen-specific T(H)2 cytokine responses, increased
      antigen-specific serum IgE levels, and accumulation of mast cells in the
      intestine, promoting the development of intestinal food allergy. Critically,
      disruption of TSLP responses or depletion of basophils reduced the susceptibility
      to intestinal food allergy, whereas transfer of TSLP-elicited basophils into
      intact skin promoted disease. CONCLUSION: Epicutaneous sensitization on a
      disrupted skin barrier is associated with accumulation of TSLP-elicited
      basophils, which are necessary and sufficient to promote antigen-induced
      intestinal food allergy.

PMID- 24560415
TI  - Transcatheter valve-in-valve tricuspid valve replacement via internal jugular and
      femoral approaches.

PMID- 24560416
TI  - Intermediate-term oncologic outcomes after video-assisted thoracoscopic
      thymectomy for early-stage thymoma.
AB  - OBJECTIVE: To evaluate the impact on patient survival of video-assisted
      thoracoscopic surgery (VATS) thymectomy for the treatment of early-stage thymoma,
      by comparing the intermediate-term oncologic outcomes with outcomes after open
      thymectomy. METHODS: Eighty-two patients who underwent complete resection of a
      Masaoka stage I or II thymoma between November 1998 and December 2011 were
      reviewed. RESULTS: The patients included 32 men and 50 women (median age, 57
      years; range, 20-90 years), of whom 44 had stage I thymoma and 38 had stage II
      thymoma. Seventy-one patients underwent VATS, of whom 4 (5.6%) underwent
      conversion to open thymectomy; the remaining 11 patients underwent planned open
      thymectomy. Thirty-six patients underwent total thymectomy and 46 underwent
      partial thymectomy. Operative mortality was nil. The tumor stage, tumor size, and
      proportion of patients who underwent total thymectomy were not significantly
      different between the open and VATS thymectomy groups. The median follow-up
      period was 49 months (VATS, 48 months; open, 52 months). There was a significant
      difference between the 2 groups for the estimated 5-year overall survival (VATS,
      97.0%; open, 79.5%; P=.041) but not in the estimated 5-year recurrence-free
      survival. CONCLUSIONS: Our findings indicate that the intermediate-term oncologic
      outcomes after VATS thymectomy for early-stage thymoma are as favorable as
      outcomes after open thymectomy. Further follow-up is still required to evaluate
      the long-term outcomes after VATS thymectomy.

PMID- 24560417
TI  - Ascending aorta dilation in association with bicuspid aortic valve: a maturation
      defect of the aortic wall.
AB  - OBJECTIVE: Patients with a bicuspid aortic valve have increased susceptibility to
      the development of ascending aortic dilation and dissection compared with persons
      with a tricuspid valve. To unravel a possible different mechanism underlying
      dilation in bicuspidy and tricuspidy, a comparison of the structure of the aortic
      wall was made. METHODS: Ascending aortic wall biopsies were divided into 4
      groups: bicuspid (n=36) and tricuspid (n=23) without and with dilation. The
      expression of vascular smooth muscle cell maturation markers including lamin A/C,
      which plays a pivotal role in smooth muscle cell differentiation, and its
      splicing variant progerin indicative of aging, were studied
      immunohistochemically. Attention was also paid to the inflammatory status.
      RESULTS: There is a significant difference in the structure and maturation of the
      aortic wall in bicuspidy, persisting in the dilated aortic wall, presenting with
      a thinner intima, lower expression of alpha smooth muscle actin, smooth muscle
      22alpha, calponin, and almost absent expression of smoothelin. We show for the
      first time significantly lowered lamin A/C expression in bicuspidy. Progerin was
      found to be significantly increased in the media of the dilated wall in
      tricuspidy, also showing increased periaortic inflammation. CONCLUSIONS: The
      structure of the nondilated and dilated aortic wall in bicuspidy and tricuspidy
      are intrinsically different, with the latter having more aspects of aging. In
      bicuspidy there is a defective smooth muscle cell differentiation possibly linked
      to lowered lamin A/C expression. Based on this vessel wall immaturity and
      increased susceptibility to dilation, different diagnostic and therapeutic
      approaches are warranted.

PMID- 24560418
TI  - Combined endovascular and surgical approach for aortobronchial fistula.
AB  - OBJECTIVE: The perioperative outcomes of the endovascular approach to
      aortobronchial fistula have been favorable. However, it is uncertain whether
      thoracic endovascular aneurysm repair (TEVAR) alone provides a complete and
      durable cure for an aortobronchial fistula. TEVAR does nothing to address the
      issue of the defect in the respiratory tract, leaving the patient at risk of
      aortobronchial fistula recurrence and/or stent graft infection. The authors
      believe that the bronchial defect should be addressed. METHODS: Over the last 10
      years, 5 patients were treated for an aortobronchial fistula using a combined
      endovascular and surgical approach (primary treatment in 3 patients and secondary
      after TEVAR in 2 patients). All the patients underwent emergency stent graft
      placement and concomitant (n=1) or staged (n=4) open repair including pulmonary
      resection with coverage of the stent graft using muscle or pleural flaps. All
      patients received a 6-week course of broad-spectrum intravenous antibiotics
      followed by lifelong oral antibiotics. RESULTS: All patients survived the
      surgical procedure. After a mean follow-up of 23.2 months, 4 patients are
      asymptomatic and postprocedure computed tomography scans were unremarkable. One
      patient treated for an aortobronchial fistula after TEVAR was readmitted 4 months
      after surgical conversion. Stent graft explantation and silver-coated tube graft
      replacement of the descending thoracic aorta were performed for severe
      mediastinitis with associated thoracic stent graft infection. The postoperative
      course of this patient was uneventful. CONCLUSIONS: Emergency TEVAR for an
      aortobronchial fistula is an appealing strategy for this devastating
      complication. However, to achieve a lasting result, direct contact between the
      stent graft and the pulmonary tissue should be avoided to prevent further erosive
      damage. Concomitant or staged repair should entail primary repair or resection
      and anastomosis of the bronchus and/or pulmonary resection with coverage of the
      stent graft using muscle or pleural flaps combined with broad-spectrum
      intravenous antibiotic therapy. Long-term surveillance and continued
      investigation are warranted.

PMID- 24560419
TI  - Age alone should not preclude surgery: contemporary outcomes after aortic valve
      replacement in nonagenarians.
AB  - OBJECTIVES: Advanced age plays a major role in surgical risk algorithms; however,
      the outcomes data for the very elderly are lacking. We, therefore, evaluated the
      outcomes after surgical aortic valve replacement (SAVR) in nonagenarians (age,
      >90 years) at our institution during an 11-year period. METHODS: The
      demographics, procedural details, and in-hospital outcomes were retrospectively
      analyzed for 119 nonagenarians with symptomatic, severe aortic stenosis who had
      undergone SAVR or SAVR plus concomitant surgery from 2001 to 2012. The mean
      follow-up period was 915+/-832 days. RESULTS: The average age was 91.7+/-1.9
      years (range, 90-98), and the mean Society of Thoracic Surgeons score was 8.9+/
      5.7. The mean aortic valve gradient was 45+/-16 mm Hg, mean aortic valve area was
      0.66+/-0.2 cm2, and mean ejection fraction was 49.8%+/-11.8%; 47% underwent
      isolated SAVR. The average length of stay was longer than expected; however, the
      rates of prolonged ventilation (16.8%), new atrial fibrillation (43.7%), stroke
      (0.8%), and renal failure (5.9%) were acceptable. Three patients (2.5%) required
      reoperation for bleeding. Overall, the 30-day and 1-year mortality was 7.6% and
      21.0%, respectively. The multivariate predictors of mortality at 1 year included
      previous myocardial infarction (hazard ratio, 2.79; 95% confidence interval, 1.21
      6.45; P=.016), obstructive lung disease (hazard ratio, 3.90; 95% confidence
      interval, 1.66-9.15; P=.025), and diabetes (hazard ratio, 2.77; 95% confidence
      interval, 1.08-7.07; P=.033). The observed in-hospital mortality was lower than
      expected (observed/expected, 0.85). CONCLUSIONS: Excellent procedural and long
      term outcomes can be achieved in nonagenarians, and age alone should not be a
      contraindication to SAVR in selected populations. Our sample cohort has validated
      the feasibility of a primary operative strategy in elderly patients with aortic
      stenosis and acceptable risk profiles.

PMID- 24560420
TI  - Disulfide bond exchanges in integrins alphaIIbbeta3 and alphavbeta3 are required
      for activation and post-ligation signaling during clot retraction.
AB  - BACKGROUND: Integrin alphaIIbbeta3 mediates platelet adhesion, aggregation and
      fibrin clot retraction. These processes require activation of alphaIIbbeta3 and
      post-ligation signaling. Disulfide bond exchanges are involved in alphaIIbbeta3
      and alphavbeta3 activation. METHODS: In order to investigate the role of integrin
      activation and disulfide bond exchange during alphaIIbbeta3- and alphavbeta3
      mediated clot retraction, we co-expressed in baby hamster kidney cells wild-type
      (WT) human alphaIIb and WT or mutated human beta3 that contain single or double
      cysteine substitutions disrupting C523-C544 or C560-C583 bonds. Flow cytometry
      was used to measure surface expression and activation state of the integrins.
      Time-course of fibrin clot retraction was examined. RESULTS: Cells expressed WT
      or mutated human alphaIIbbeta3 as well as chimeric hamster/human alphavbeta3. The
      alphaIIbbeta3 mutants were constitutively active and the thiol blocker
      dithiobisnitrobenzoic acid (DTNB) did not affect their activation state. WT cells
      retracted the clot and addition of alphavbeta3 inhibitors decreased the
      retraction rate. The active mutants and WT cells activated by anti-LIBS6 antibody
      retracted the clot faster than untreated WT cells, particularly in the presence
      of alphavbeta3 inhibitor. DTNB substantially inhibited clot retraction by WT or
      double C523S/C544S mutant expressing cells, but minimally affected single C523S,
      C544S or C560S mutants. Anti-LIBS6-enhanced clot retraction was significantly
      inhibited by DTNB when added prior to anti-LIBS6. CONCLUSIONS: Both alphaIIbbeta3
      and alphavbeta3 contribute to clot retraction without prior activation of the
      integrins. Activation of alphaIIbbeta3, but not of alphavbeta3 enhances clot
      retraction. Both alphaIIbbeta3 activation and post-ligation signaling during clot
      retraction require disulfide bond exchange.

PMID- 24560421
TI  - High coagulation factor levels and low protein C levels contribute to enhanced
      thrombin generation in patients with diabetes who do not have macrovascular
      complications.
AB  - AIMS: A prothrombotic state characterized by activation of the coagulation system
      has been implicated in the pathogenesis of vascular complications in diabetes
      mellitus. Recently, a thrombin generation assay was introduced as a laboratory
      assessment of global hemostatic potential. We used this thrombin generation assay
      to investigate global hemostatic potential in patients with diabetes who did not
      have macrovascular complications. METHODS: This study was a prospective case
      control study comparing 89 patients with diabetes with 49 healthy controls. The
      thrombin generation assay was conducted with the calibrated automated thrombogram
      using tissue factor with or without the addition of thrombomodulin, giving values
      for lag time, endogenous thrombin potential, and peak thrombin. RESULTS: Patients
      with diabetes showed hypercoagulability, as detected by the thrombin generation
      assay, compared with healthy controls. Correspondingly, high levels of
      coagulation factors (II, V, VII, VIII, and X) and low levels of anticoagulant
      (protein C) were major contributing factors in this hypercoagulability.
      Interestingly, a high blood glucose level was correlated with shortened clotting
      time, reflecting the association between hyperglycemia and hypercoagulability.
      Patients who were taking statins or angiotensin receptor blockers showed
      decreased endogenous thrombin potential ratio and increased protein C levels,
      suggesting relative hypocoagulability. CONCLUSIONS: Patients with diabetes showed
      hypercoagulability, high levels of coagulation factors, and low levels of protein
      C. Further study is required to investigate how this hemostatic potential may be
      used to guide physicians toward more effective management of hemostatic
      complications.

PMID- 24560423
TI  - Association of myocardial dysfunction with vitamin D deficiency in patients with
      type 2 diabetes mellitus.
AB  - AIMS: The underlying mechanism of myocardial dysfunction in patients with type 2
      diabetes mellitus (T2DM) is unclear. Nonetheless recent studies have revealed
      that vitamin D (vit-D) deficiency, which is prevalent in such patients, is
      associated with adverse cardiovascular events. We hypothesized that vit-D
      deficiency in patients with T2DM may contribute to left ventricular (LV)
      dysfunction. METHODS: We studied 95 patients (62+/-9years, 58% female) with T2DM.
      None had any history of coronary artery disease and all underwent detailed
      transthoracic echocardiography, including speckle tracking derived strains.
      Plasma level of 25-hydoxyvitamin D (25-OHD) was also measured. RESULTS: Vitamin D
      deficiency was evident in 60 (63%) patients. The LV dimension, LVEF and diastolic
      grade were similar between those with and without deficiency although an impaired
      global longitudinal strain was present in the former. Importantly, 25-OHD was
      negatively associated with global longitudinal strain (R = -0.21, P=0.046) and
      positively with body-mass index (BMI; R=0.26, P=0.01). Both vit-D deficiency and
      BMI were associated with impaired global LV longitudinal strain, independent of
      T2DM disease characteristics. CONCLUSIONS: In patients with T2DM and no history
      of coronary artery disease, vit-D deficiency is independently associated with
      impaired global longitudinal strain. This suggests that vit-D deficiency may
      contribute to the development of myocardial dysfunction in these patients.

PMID- 24560425
TI  - Susceptibility of 45 Streptococcus bovis isolates to five antibiotic agents.

PMID- 24560426
TI  - Importance of chemical modification at C-7 position of quinolones for glutathione
      mediated reversal of antibacterial activity.

PMID- 24560424
TI  - Association of reduced levels of serum 1,5-Anhydro-d-glucitol with carotid
      atherosclerosis in patients with type 2 diabetes.
AB  - BACKGROUND: HbA1c level represents mean blood glycemic control. 1,5-Anhydro-d
      glucitol (1,5-AG) level reflects glycemic fluctuations, a strong risk factor for
      the development of macroangiopathy. The present study investigated the
      relationship between serum 1,5-AG levels and macroangiopathy in patients with
      type 2 diabetes. METHODS: A total of 115 consecutive patients with type 2
      diabetes, aged 45-79 years, were included. HbA1c, 1,5-AG, and lipid profile were
      measured. Carotid maximum intima-media thickness (IMT) and plaque score (PS) were
      determined by carotid sonography. An 1,5-AG level < 14.2 MUg/mL was used as a
      predictor of a post-challenge 2-h blood glucose level > 200 mg/dL. Patients were
      divided into four groups: A (n=32), HbA1c >= 6.5% and 1,5-AG<14.2 MUg/mL; B
      (n=23), HbA1c >= 6.5% and 1,5-AG >= 14.2 MUg/mL; C (n=24), HbA1c < 6.5% and 1,5
      AG <14.2 MUg/mL; and D (n=36), HbA1c < 6.5% and 1,5-AG >= 14.2 MUg/mL. RESULTS:
      HbA1c level had significant positive correlation with IMT and PS. 1,5-AG level
      had a significant negative correlation with PS. PS was significantly higher in
      group C than in group D, but similar to that in group B. In multivariate
      analysis, HbA1c (beta=0.27, p=0.03) and 1,5-AG (beta=-0.24, P=0.04) were
      independent determinants of PS. CONCLUSIONS: 1,5-AG level might provide
      additional information to identify macroangiopathy of patients with type 2
      diabetes, especially in those with excellent HbA1c levels.

PMID- 24560422
TI  - Clinical correlates of serum pigment epithelium-derived factor in type 2 diabetes
      patients.
AB  - AIM: To determine if serum pigment epithelium-derived factor (PEDF) levels in
      Type 2 diabetes are related to vascular risk factors and renal function. METHODS:
      PEDF was quantified by ELISA in a cross-sectional study of 857 male Veterans
      Affairs Diabetes Trial (VADT) subjects, and associations with cardiovascular risk
      factors and renal function were determined. In a subset (n=246) in whom serum was
      obtained early in the VADT (2.0+/-0.3 years post-randomization), PEDF was related
      to longitudinal changes in renal function over 3.1 years. RESULTS: Cross
      sectional study: In multivariate regression models, PEDF was positively
      associated with serum triglycerides, waist-to-hip ratio, serum creatinine, use of
      ACE inhibitors or angiotensin receptor blockers, and use of lipid-lowering
      agents; it was negatively associated with HDL-C (all p<0.05). Longitudinal study:
      PEDF was not associated with changes in renal function over 3.1 years (p>0.09).
      CONCLUSIONS: Serum PEDF in Type 2 diabetic men was cross-sectionally associated
      with dyslipidemia, body habitus, use of common drugs for blood pressure and
      dyslipidemia, and indices of renal function; however, PEDF was not associated
      with renal decline over 3.1years.

PMID- 24560427
TI  - Secondary use of existing public microarray data to predict outcome for
      hepatocellular carcinoma.
AB  - BACKGROUND: Since 1990, numerous public repositories of microarray data have been
      created to store vast genomic data sets. Our hypothesis is that a secondary
      analysis of an available hepatocellular carcinoma (HCC) public data set could
      generate new findings and additional hypotheses. METHODS: The Gene Expression
      Omnibus at the National Center for Biotechnology Information was queried for
      available data sets specific for 'HCC' and 'clinical data.' Genes that passed
      filtering and normalization criteria were analyzed using the class comparison and
      prediction functions in BRB-ArrayTools. Ingenuity pathway analysis software was
      used to identify potential gene networks up- or down-regulated. RESULTS: The file
      GDS274, which measured gene expression in primary HCC lesions with or without
      hepatic metastases from a cohort of Chinese patients, was identified as an
      appropriate data set and was imported into BRB-ArrayTools. 9984 genes passed
      filtering criteria. Clinical data demonstrated alpha fetoprotein (AFP) >100 ng/mL
      predictive of worse survival (HR 5.87, 95% confidence interval: 1.11-31.0). A
      class comparison between patients with an AFP >100 and those with AFP <100
      demonstrated 92 genes to be differentially expressed. Ingenuity pathway analyses
      demonstrated the top networks associated with the observed gene expression.
      CONCLUSIONS: Using available HCC microarray data, we identified genes
      differentially expressed based on AFP >100. Canonical pathway analysis
      demonstrated functional gene pathways and associated upstream regulators. This
      study maximizes the use of publicly available data by generating new findings.
      Secondary analyses of these data sets should be considered by investigators
      before embarking on new genomic experiments.

PMID- 24560428
TI  - Review of stoma site and midline incisional hernias after stoma reversal.
AB  - BACKGROUND: The incidence of incisional hernias after stoma reversal is not well
      reported. The aim of this study was to systematically review the literature
      reporting data on incisional hernias after stoma reversal. We evaluated both the
      incidence of stoma site and midline incisional hernias. METHODS: A systematic
      review identified studies published between January 1, 1980, and December 31,
      2012, reporting the incidence of incisional hernia after stoma reversal at either
      the stoma site or at the midline incision (in cases requiring laparotomy).
      Pediatric studies were excluded. Assessment of risk of bias, detection method,
      and essential study-specific characteristics (follow-up duration, stoma type,
      age, body mass index, and so forth) was done. RESULTS: Sixteen studies were
      included in the analysis; 1613 patients had 1613 stomas formed. Fifteen studies
      assessed stoma site hernias and five studies assessed midline incisional hernias.
      The median (range) incidence of stoma site incisional hernias was 8.3% (range 0%
      33.9%) and for midline incisional hernias was 44.1% (range 8.7%-58.1%). When
      evaluating only studies with a low risk of bias, the incidence for stoma site
      incisional hernias is closer to one in three and for midline incisional hernias
      is closer to one in two. CONCLUSION: Stoma site and midline incisional hernias
      are significant clinical complications of stoma reversals. The quality of studies
      available is poor and heterogeneous. Future prospective randomized controlled
      trials or observational studies with standardized follow-up and outcome
      definitions/measurements are needed.

PMID- 24560429
TI  - Microperforation of the colon: animal model in rats to reproduce mucosal thermal
      damage.
AB  - BACKGROUND: The aim of the present study was to develop a rat model of colonic
      microperforation secondary to thermal injury for future studies to assess new
      treatments. METHODS: Twenty-four male Sprague-Dawley rats were used in this
      study. Hot biopsy forceps were used for all treatments. All lesions were created
      in proximal left colon using the soft coagulation setting. The power setting
      tested was 40 W, and the durations of monopolar soft coagulation application
      evaluated were 2, 3, and 4 s. RESULTS: In the acute phase, 48 h after thermal
      injury, durations of cautery of 2 and 3 s resulted in transmural necrosis,
      whereas with 4 s microperforation was obtained. In the late phase, 7 d after the
      damage, only duration of cautery of 4 s showed deep cautery effects, with signs
      of peritonitis. CONCLUSIONS: We determined optimal power settings and duration of
      therapy in a rat model for producing electrocautery that involves transmural
      necrosis with microperforation.

PMID- 24560430
TI  - The mismatch negativity: a translational probe of auditory processing in cannabis
      users.

PMID- 24560431
TI  - Different dopaminergic abnormalities underlie cannabis dependence and cannabis
      induced psychosis.

PMID- 24560432
TI  - A discount on cannabinoids.

PMID- 24560433
TI  - Utility of optical facial feature and arm movement tracking systems to enable
      text communication in critically ill patients who cannot otherwise communicate.
AB  - PURPOSE: Patients recovering from critical illness especially those with critical
      illness related neuropathy, myopathy, or burns to face, arms and hands are often
      unable to communicate by writing, speech (due to tracheostomy) or lip reading.
      This may frustrate both patient and staff. Two low cost movement tracking systems
      based around a laptop webcam and a laser/optical gaming system sensor were
      utilised as control inputs for on-screen text creation software and both were
      evaluated as communication tools in volunteers. METHODS: Two methods were used to
      control an on-screen cursor to create short sentences via an on-screen keyboard:
      (i) webcam-based facial feature tracking, (ii) arm movement tracking by
      laser/camera gaming sensor and modified software. 16 volunteers with simulated
      tracheostomy and bandaged arms to simulate communication via gross movements of a
      burned limb, communicated 3 standard messages using each system (total 48 per
      system) in random sequence. RESULTS: Ten and 13 minor typographical errors
      occurred with each system respectively, however all messages were comprehensible.
      Speed of sentence formation ranged from 58 to 120s with the facial feature
      tracking system, and 60-160s with the arm movement tracking system. The average
      speed of sentence formation was 81s (range 58-120) and 104s (range 60-160) for
      facial feature and arm tracking systems respectively, (P<0.001, 2-tailed
      independent sample t-test). CONCLUSION: Both devices may be potentially useful
      communication aids in patients in general and burns critical care units who
      cannot communicate by conventional means, due to the nature of their injuries.

PMID- 24560434
TI  - Burn resuscitation on the African continent.
AB  - A survey of members of the International Society of Burn Injuries (ISBI) and the
      American Burn Association (ABA) indicated that although there was difference in
      burn resuscitation protocols, they all fulfilled their functions. This study
      presents the findings of the same survey replicated in Africa, the only continent
      not included in the original survey. One hundred and eight responses were
      received. The mean annual number of admissions per unit was ninety-eight. Fluid
      resuscitation was usually initiated with total body surface area burns of either
      more than ten or more than fifteen percent. Twenty-six respondents made use of
      enteral resuscitation. The preferred resuscitation formula was the Parkland
      formula, and Ringer's Lactate was the favoured intravenous fluid. Despite
      satisfaction with the formula, many respondents believed that patients received
      volumes that differed from that predicted. Urine output was the principle guide
      to adequate resuscitation, with only twenty-one using the evolving clinical
      picture and thirty using invasive monitoring methods. Only fifty-one respondents
      replied to the question relating to the method of adjusting resuscitation. While
      colloids are not available in many parts of the African continent on account of
      cost, one might infer than African burn surgeons make better use of enteral
      resuscitation. 

PMID- 24560435
TI  - Effect of ankle taping on angle and force matching and strength of the plantar
      flexors.
AB  - OBJECTIVE: Investigate the effect of ankle taping on plantar-flexion strength,
      angle matching and force matching. DESIGN: Single group, repeated measures.
      SETTING: Laboratory of an educational institution. PARTICIPANTS: Twenty uninjured
      females (22.9 +/- 3.6 years). MAIN OUTCOME MEASURES: Tape was applied to the
      ankle using a conventional hindfoot technique. Angle and force matching, and
      plantar-flexor strength were assessed using the purpose built dual ankle
      dynamometer, and measures were taken prior to and following taping. Angle
      matching was assessed passively and actively at 10, 15 and 20 degrees  of plantar
      flexion. Participants were required to match the angle of the reference leg with
      the contralateral leg. Force matching was assessed at 10 degrees  of plantar
      flexion and participants matched the torque of the reference leg with the
      contralateral leg. RESULTS: Taping had no effect on absolute errors during active
      or passive angle matching. Regardless of taping, the ankle angle tested had a
      significant effect on passive angle matching (p < 0.001); subjects were most
      accurate at matching a plantar-flexion angle of 20 degrees . Ankle taping had no
      effect on force matching. Taping significantly improved peak plantar-flexion
      strength by 20% (p = 0.028). CONCLUSION: Ankle taping has little effect on
      contralateral force and angle matching, but it can enhance peak plantar-flexion
      strength.

PMID- 24560436
TI  - Non-selective cation channels in plasma and vacuolar membranes and their
      contribution to K+ transport.
AB  - Both in vacuolar and plasma membranes, in addition to truly K(+)-selective
      channels there is a variety of non-selective channels, which conduct K(+) and
      other ions with little preference. Many non-selective channels in the plasma
      membrane are active at depolarized potentials, thus, contributing to K(+) efflux
      rather than to K(+) uptake. They may play important roles in xylem loading or
      contribute to a K(+) leak, induced by salt or oxidative stress. Here, three
      currents, expressed in root cells, are considered: voltage-insensitive cation
      current, non-selective outwardly rectifying current, and low-selective
      conductance, activated by reactive oxygen species. The latter two do not only
      poorly discriminate between different cations (like K(+)vs Na(+)), but also
      conduct anions. Such solute channels may mediate massive electroneutral transport
      of salts and might be involved in osmotic adjustment or volume decrease,
      associated with cell death. In the tonoplast two major currents are mediated by
      SV (slow) and FV (fast) vacuolar channels, respectively, which are virtually
      impermeable for anions. SV channels conduct mono- and divalent cations
      indiscriminately and are activated by high cytosolic Ca(2+) and depolarized
      voltages. FV channels are inhibited by micromolar cytosolic Ca(2+), Mg(2+), and
      polyamines, and conduct a variety of monovalent cations, including K(+).
      Strikingly, both SV and FV channels sense the K(+) content of vacuoles, which
      modulates their voltage dependence, and in case of SV, also alleviates channel's
      inhibition by luminal Ca(2+). Therefore, SV and FV channels may operate as K(+)
      sensing valves, controlling K(+) distribution between the vacuole and the
      cytosol. 

PMID- 24560437
TI  - Predictors and treatment outcomes of perceived ward atmosphere among therapeutic
      community residents.
AB  - Poor retention has been an impediment to the effectiveness of therapeutic
      communities (TCs) for substance use disorders. We assessed the impact of the
      resident's perception of the therapeutic environment through the Ward Atmosphere
      Scale (WAS) on TC retention and examined predictors of the WAS in order to better
      understand this construct. Among a sample of admissions (N=123) to a 9-month
      residential TC, forward entry logistic regression analyses using WAS, demographic
      and clinical variables revealed that heightened perceptions of the orderliness of
      the therapeutic environment (i.e., the WAS domain of system maintenance) best
      predicted treatment completion. Furthermore, scores on WAS variables were best
      explained by the formal therapeutic elements of the TC (as measured by the Survey
      of Essential Elements Questionnaire) using linear regression. Efforts to improve
      the resident's perception of these aspects of the ward atmosphere may assist in
      improving TC completion rates. 

PMID- 24560438
TI  - A placebo-controlled trial of memantine as an adjunct to injectable extended
      release naltrexone for opioid dependence.
AB  - There is preclinical support for using NMDA receptor glutamatergic antagonists to
      aid in naltrexone-based treatment of opioid dependence. We hypothesized that
      adding memantine will improve efficacy of extended-release (XR) naltrexone to
      prevent relapse. In this double blind study opioid-dependent participants (N=82)
      underwent inpatient detoxification and naltrexone induction. During naltrexone
      initiation participants were randomized to receive memantine 40 mg or placebo and
      continued treatment for 12-weeks with XR naltrexone and relapse-prevention
      therapy. Sixty eight percent of participants completed detoxification and
      received the first dose of XR naltrexone. Rates of trial completion were
      significantly greater in participants receiving placebo than memantine (70% vs.
      43%, p<0.05). Severity of opioid withdrawal symptoms during the first 3 weeks of
      the trial appeared to be lower in the group receiving memantine (p=0.07). Adding
      memantine does not appear to increase the effectiveness of injectable XR
      naltrexone as a relapse prevention strategy in opioid dependence and may lead to
      an increase in treatment drop-out.

PMID- 24560439
TI  - [Gastroenteropancreatic neuroendocrine tumors: clinical characteristics,
      diagnosis and prognosis at Hospital Universitario Clinico San Carlos (Madrid)].
AB  - INTRODUCTION: Neuroendocrine tumors are a group of neoplasms arising from the
      neural crest and endoderm and very heterogeneous as regards localization,
      clinical behavior, aggressiveness, and prognosis. Pancreas and gastrointestinal
      tract are the most common sites where neuroendocrine tumors can be found.
      MATERIAL AND METHODS: A review was made of all cases of neuroendocrine tumors
      diagnosed at Hospital Universitario Clinico San Carlos (HUCSC) from January 2007
      to May 2012. Data were compared to the results provided by the Registry of the
      Spanish Group on Neuroendocrine Tumors (RGETNE). RESULTS: The study cohort
      comprised 78 patients. Gastroenteric nonfunctional tumors were the most common
      neoplasms. Metastases were found at diagnosis in50.6% of patients, with nodal
      involvement being most prevalent. Tumors located in the rectum were associated to
      the highestrate of metastasis. Overall 2-year survival rate was 74.8% and was
      related to sex, Ki-67 expression, and presence of metastasis.

PMID- 24560440
TI  - BikeSafe: evaluating a bicycle safety program for middle school aged children.
AB  - PURPOSE: The purpose of this study is to measure the effectiveness of a bicycle
      safety education curriculum for middle school age children in order to reduce the
      number of injuries and fatalities of bicyclists hit by cars in Miami-Dade County.
      METHODS: The University of Miami BikeSafe((r)) program includes a four day off
      bike middle school curriculum that follows a train-the-trainer model, where a
      small number of staff trains a larger group of grades 6th-8th physical education
      teachers from various schools to teach the bike safety curriculum to their
      students. Subjects in this study included 193 students from 18 classes (3 per
      school) at 6 selected middle schools. Measures included a knowledge assessment of
      the curriculum that was administered to students pre- and post-curriculum
      implementation. Data were collected and analyzed with school and class period
      examined as predictors of post-score. RESULTS: A significant difference (p<.001)
      was found between pre- and post-test conditions across all subjects. In addition,
      there was no significant difference between testing from class periods (p>.05),
      suggesting that a standard intervention was applied. CONCLUSION: The BikeSafe
      educational curriculum was found to improve the bike safety knowledge of middle
      school aged children. Future efforts will focus on sustaining and expanding this
      program throughout Miami-Dade County and other high risk communities.

PMID- 24560441
TI  - Early comprehension of the Spanish plural.
AB  - Understanding how linguistic cues map to the environment is crucial for early
      language comprehension and may provide a way for bootstrapping and learning
      words. Research has suggested that learning how plural syntax maps to the
      perceptual environment may show a trajectory in which children first learn
      surrounding cues (verbs, modifiers) before a full mastery of the noun morpheme
      alone. The Spanish plural system of simple codas, dominated by one allomorph -s,
      and with redundant agreement markers, may facilitate early understanding of how
      plural linguistic cues map to novel referents. Two-year-old Mexican children
      correctly identified multiple novel object referents when multiple verbal cues in
      a phrase indicated plurality as well as in instances when the noun morphology in
      novel nouns was the only indicator of plurality. These results demonstrate
      Spanish-speaking children's ability to use plural noun inflectional morphology to
      infer novel word referents which may have implications for their word learning.

PMID- 24560442
TI  - Variations of the vertebrobasilar circulation and its impact on the neurosurgical
      interventions.

PMID- 24560443
TI  - Immunohistochemical expression of aberrant Notch-1 signaling in vitiligo: an
      implication for pathogenesis.
AB  - The etiopathogenetic mechanisms leading to pigment loss in vitiligo are not fully
      understood. Notch signaling is required for development and maintenance of
      melanocyte lineage and acts as a key component among keratinocyte-melanocyte
      interactions. The current study aimed to investigate the possible role of Notch
      signaling and its effect on the whole melanocyte lineage in vitiligo and
      correlating it with the different clinicopathologic parameters. Using
      immunohistochemical technique, Notch-1 expression was evaluated in 50 lesional
      and 20 perilesional biopsies of patients with vitiligo in comparison with 20
      normal skin biopsies as a control group. Lesional biopsies were stained with
      human melanoma black-45 and tyrosinase-related protein-2 to demonstrate the
      melanocyte lineage. Membranous and/or nuclear expression of Notch-1 was in favor
      of control and perilesional skin, whereas cytoplasmic expression appeared only in
      vitiliginous lesions (P < .05). Membranous and/or nuclear expression of Notch-1
      was significantly associated with epidermal human melanoma black-45 positivity (P
      = .01) and percentage of expression in both epidermis (P = .02) and hair
      follicles (P = .03) of lesional skin. Cytoplasmic pattern of Notch-1 expression
      in epidermis was significantly found in lesions with white hair (P = .04) and in
      cases with marked keratinocyte vacuolization (P = .03). Segmental and acrofacial
      vitiligo were associated with mild to moderate Notch-1 intensity, whereas
      generalized vitiligo was associated with strong intensity of expression (P =
      .02). In conclusion, Notch-1 signaling is inactivated in vitiligo with consequent
      loss of epidermal and/or follicular active melanocytes. Aberrant Notch signaling
      in vitiliginous white hair and acral and segmental vitiligo may be the cause of
      their treatment resistance. 

PMID- 24560444
TI  - Promoter CpG island methylation of RET predicts poor prognosis in stage II
      colorectal cancer patients.
AB  - Improved prognostic stratification of patients with TNM stage II colorectal
      cancer (CRC) is desired, since 20-30% of high-risk stage II patients may die
      within five years of diagnosis. This study was conducted to investigate
      REarranged during Transfection (RET) gene promoter CpG island methylation as a
      possible prognostic marker for TNM stage II CRC patients. The utility of RET
      promoter CpG island methylation in tumors of stage II CRC patients as a
      prognostic biomarker for CRC related death was studied in three independent
      series (including 233, 231, and 294 TNM stage II patients, respectively) by using
      MSP and pyrosequencing. The prognostic value of RET promoter CpG island
      methylation was analyzed by using Cox regression analysis. In the first series,
      analyzed by MSP, CRC stage II patients (n = 233) with RET methylated tumors had a
      significantly worse overall survival as compared to those with unmethylated
      tumors (HRmultivariable = 2.51, 95%-CI: 1.42-4.43). Despite a significant
      prognostic effect of RET methylation in stage III patients of a second series,
      analyzed by MSP, the prognostic effect in stage II patients (n = 231) was not
      statistically significant (HRmultivariable = 1.16, 95%-CI 0.71-1.92). The third
      series (n = 294), analyzed by pyrosequencing, confirmed a statistically
      significant association between RET methylation and poor overall survival in
      stage II patients (HRmultivariable = 1.91, 95%-CI: 1.04-3.53). Our results show
      that RET promoter CpG island methylation, analyzed by two different techniques,
      is associated with a poor prognosis in stage II CRC in two independent series and
      a poor prognosis in stage III CRC in one series. RET methylation may serve as a
      useful and robust tool for clinical practice to identify high-risk stage II CRC
      patients with a poor prognosis. This merits further investigation.

PMID- 24560447
TI  - Cryotherapy for oral precancers and cancers.
AB  - Previous studies have used cryotherapy for the treatment of oral precancers
      including oral leukoplakia (OL) and oral verrucous hyperplasia (OVH) as well as
      oral cancers including oral verrucous carcinoma (OVC) and oral squamous cell
      carcinoma (OSCC). Cryotherapy is a method that locally destroys lesional tissues
      by freezing in situ. It can be carried out by either an "open" or a "closed"
      system. Lesional tissues are destroyed mainly through disruption of cell
      membrane, cellular dehydration, enzyme and protein damage, cell swelling and
      rupture, thermal shock injury to cells, damage to vasculature, and immune
      mediated cytotoxicity. Cryotherapy is used frequently for the treatment of OL
      lesions with promising results. It can also be used to treat OVH and OVC lesions.
      Because OVH and OVC lesions are usually fungating and bulky, a combination
      therapy of shave excision and cryotherapy is needed to achieve a complete
      regression of the lesion. OSCCs have also been treated by cryotherapy. However,
      cryotherapy is not the main-stream treatment modality for OSCCs. Cryotherapy
      seems suitable for treatment of thin or relatively thick plaque-typed lesions
      such as OL lesions. By careful selection of patients, cryotherapy is a simple,
      safe, easy, conservative, and acceptable treatment modality for certain benign
      oral lesions and oral precancers. 

PMID- 24560445
TI  - Molecular correlates of platinum response in human high-grade serous ovarian
      cancer patient-derived xenografts.
AB  - INTRODUCTION: Improvement in the ability to target underlying drivers and
      vulnerabilities of high-grade serous ovarian cancer (HG-SOC) requires the
      development of molecularly annotated pre-clinical models reflective of clinical
      responses. METHODS: We generated patient-derived xenografts (PDXs) from
      consecutive, chemotherapy-naive, human HG-SOC by transplanting fresh human HG-SOC
      fragments into subcutaneous and intra-ovarian bursal sites of NOD/SCID
      IL2Rgamma(null) recipient mice, completed molecular annotation and assessed
      platinum sensitivity. RESULTS: The success rate of xenografting was 83%. Of ten
      HG-SOC PDXs, all contained mutations in TP53, two were mutated for BRCA1, three
      for BRCA2, and in two, BRCA1 was methylated. In vivo cisplatin response,
      determined as platinum sensitive (progression-free interval >= 100 d, n = 4),
      resistant (progression-free interval <100 d, n = 3) or refractory (n = 3), was
      largely consistent with patient outcome. Three of four platinum sensitive HG-SOC
      PDXs contained DNA repair gene mutations, and the fourth was methylated for
      BRCA1. In contrast, all three platinum refractory PDXs overexpressed dominant
      oncogenes (CCNE1, LIN28B and/or BCL2). CONCLUSIONS: Because PDX platinum response
      reflected clinical outcome, these annotated PDXs will provide a unique model
      system for preclinical testing of novel therapies for HG-SOC.

PMID- 24560448
TI  - Brain stem lesion in mitochondrial DNA G11778A mutation of Leber's hereditary
      optic neuropathy.

PMID- 24560446
TI  - Validation of a prognostic multi-gene signature in high-risk neuroblastoma using
      the high throughput digital NanoString nCounterTM system.
AB  - Microarray-based molecular signatures have not been widely integrated into
      neuroblastoma diagnostic classification systems due to the complexities of the
      assay and requirement for high-quality RNA. New digital technologies that
      accurately quantify gene expression using RNA isolated from formalin-fixed
      paraffin embedded (FFPE) tissues are now available. In this study, we describe
      the first use of a high-throughput digital system to assay the expression of
      genes in an "ultra-high risk" microarray classifier in FFPE high-risk
      neuroblastoma tumors. Customized probes corresponding to the 42 genes in a
      published multi-gene neuroblastoma signature were hybridized to RNA isolated from
      107 FFPE high-risk neuroblastoma samples using the NanoString nCounterTM Analysis
      System. For classification of each patient, the Pearson's correlation coefficient
      was calculated between the standardized nCounterTM data and the molecular
      signature from the microarray data. We demonstrate that the nCounterTM 42-gene
      panel sub-stratified the high-risk cohort into two subsets with statistically
      significantly different overall survival (p = 0.0027) and event-free survival (p
      = 0.028). In contrast, none of the established prognostic risk markers (age,
      stage, tumor histology, MYCN status, and ploidy) were significantly associated
      with survival. We conclude that the nCounterTM System can reproducibly quantify
      expression levels of signature genes in FFPE tumor samples. Validation of this
      microarray signature in our high-risk patient cohort using a completely different
      technology emphasizes the prognostic relevance of this classifier. Prospective
      studies testing the prognostic value of molecular signatures in high-risk
      neuroblastoma patients using FFPE tumor samples and the nCounterTM System are
      warranted.

PMID- 24560449
TI  - Cyclosporine A induces connective tissue growth factor expression in human
      gingival fibroblasts: suppression by epigallocatechin-3-gallate.
AB  - BACKGROUND/PURPOSE: Transforming growth factor-beta (TGF-beta) plays an important
      role in the pathogenesis of cyclosporine A (CsA)-induced gingival overgrowth
      (GO). Connective tissue growth factor (CTGF/CCN2) acts as a cofactor with TGF
      beta to induce the maximal profibrotic effects of TGF-beta. We investigated the
      effects of CsA on CCN2 expression in human gingival fibroblasts (HGFs) and the
      potential chemopreventive agent for CsA-induced GO. METHODS: Western blot
      analyses were used to examine the signaling pathways of CsA-induced CCN2
      expression in HGFs and whether epigallocatechin-3-gallate (EGCG), curcumin, or
      lovastatin can inhibit CsA-induced CCN2 expression. RESULTS: CsA significantly
      stimulated CCN2 synthesis in HGFs. This effect can be inhibited by c-Jun NH(2)
      terminal kinase (JNK) and Smad3 inhibitors but not by TGF-beta neutralizing
      antibody and TGF-beta type I receptor inhibitor. Furthermore, EGCG completely
      blocked CsA-induced CCN2 expression. CONCLUSION: CsA-induced CCN2 protein
      expression is mediated through JNK and Smad signaling. CsA may contribute to the
      pathogenesis of GO through upregulation of CCN2 expression in HGFs. EGCG could be
      an adjuvant for the prevention of CsA-induced GO.

PMID- 24560451
TI  - Effect of reproductive tract scoring on reproductive efficiency in beef heifers
      bred by timed insemination and natural service versus only natural service.
AB  - The objective was to determine the effects of reproductive tract score (RTS) on
      reproductive performance in beef heifers bred by timed artificial insemination
      followed by natural service (AI-NS) or by natural service only (NSO). Angus cross
      beef heifers (n = 2660) in the AI-NS group were artificially inseminated at a
      fixed time (5- or 7-day CO-Synch + controlled internal drug release protocol)
      once, then exposed to bulls 2 weeks later (bull-to-heifer ratio = 1:40-1:50) for
      the reminder of the 85-day breeding season. Angus cross beef heifers (n = 1381)
      in NSO group were submitted to bulls (bull-to-heifer ratio = 1:20-1:25) for the
      entire 85-day breeding season. Heifers were reproductive tract scored from 1
      (prepubertal) to 5 (cyclic) 4 weeks before, and were body condition scored (BCS)
      from 1 (emaciated) to 9 (obese) at the beginning of breeding season. Pregnancy
      diagnosis was performed 70 days after AI for AI-NS group and 2 months after the
      end of breeding season for both groups. Heifers in both groups were well managed
      and of similar age (14.9 +/- 0.4 [AI-NS] and 14.7 +/- 0.8 [NSO] months).
      Pregnancy rates (PRs) and number of days to become pregnant were calculated using
      PROC GLIMMIX and PROC LIFETEST procedures of SAS. Adjusting for BCS (P = 0.07),
      expressed estrus (P < 0.05), year (P < 0.05), and BCS by year interaction (P <
      0.05), the AI-PR was greater for heifers in AI-NS group with higher RTS (P <
      0.0001; 40.7%, 48.3%, 57.6%, and 64.6% for RTS of 2 or less, 3, 4, and 5,
      respectively). Controlling for BCS (P < 0.05), year (P < 0.05) and the breeding
      season pregnancy rates (BS-PRs) were greater for heifers in the AI-NS group with
      higher RTS (P < 0.01; 81.2%, 86.5%, 90.4%, and 95.2% for RTS of 2 or less, 3, 4,
      and 5, respectively). Similarly, adjusting for BCS, year (P < 0.05), the BS-PR
      was greater for heifers in NSO group with higher RTS (P < 0.01; 79.7%, 84.3%,
      88.4%, and 90.2% for RTS of 2 or less, 3, 4, and 5, respectively). Heifers with
      higher RTS in both groups became pregnant earlier in the breeding season compared
      with heifers with lower RTS (log-rank statistics: P < 0.0001). Heifers in the AI
      NS group become pregnant at a faster rate compared with those in the NSO group (P
      < 0.01). The BS-PR for heifers with RTS 5 was different between AI-NS and NSO
      groups (P < 0.0001). In conclusion, the RTS influenced both the number of beef
      heifers that became pregnant during the breeding season and the time at which
      they become pregnant. Furthermore, irrespective of RTS, heifers bred by NSO
      required more time to become pregnant than their counterparts in herds that used
      timed AI. The application of RTS system is reliant on the use of synchronization
      protocol. The application of RTS for selection may plausibly remove precocious
      females with lower RTS. On the contrary, application of RTS would help select
      heifers that will become pregnant earlier in breeding season. 

PMID- 24560452
TI  - Peripheral blood leukocytes of cows with subclinical endometritis show an altered
      cellular composition and gene expression.
AB  - Subclinical endometritis (SCE) is an important postpartum disease in dairy cows,
      but conventional cytobrush diagnosis often gives imprecise results. The aim of
      this study was to analyze disease-associated changes in peripheral blood as
      potential diagnostic parameters. Cellular subpopulations of blood leukocytes from
      cows with or without SCE (45-55 days postpartum) were flow-cytometrically
      quantified. Gene expression of whole blood leukocytes was assessed by PAXgene
      analysis. Subclinical endometritis cows showed significantly higher number of
      blood mononuclear cells and neutrophils. Among mononuclear cells, numbers of B
      cells, NK-cells, and CD172a-positive monocytes were significantly elevated.
      Compared with non-SCE cows, blood leukocytes of SCE cows significantly expressed
      higher copy numbers of CXCL8, TNF, and IL12. To test whether circulating plasma
      factors are responsible for these changes, leukocytes, polymorphonuclear cells,
      and monocyte subpopulations (classical, intermediate, nonclassical) of healthy
      cows were stimulated with plasma of SCE and non-SCE cows. Although gene
      expression of whole leukocytes and polymorphonuclear cells remained unaltered,
      plasma from SCE animals significantly elevated expressed messenger RNA copy
      numbers of CXCL8, CXCL1, and IL1B in intermediate monocytes. In conclusion,
      elevated number of selected mononuclear subpopulations in peripheral blood and
      enhanced expression of distinct genes encoding for inflammatory mediators in
      blood leukocytes reflect the subclinical uterine inflammatory process in cows.
      Whether the observed changes in the periphery of SCE cows are the consequence of
      the uterine inflammatory process, or whether they affect the pathogenesis of the
      disease is currently unknown. 

PMID- 24560454
TI  - What is the effect of more sensitive diagnostic technology?

PMID- 24560453
TI  - Standard forward-viewing colonoscopy versus full-spectrum endoscopy: an
      international, multicentre, randomised, tandem colonoscopy trial.
AB  - BACKGROUND: Although colonoscopy is the accepted standard for detection of
      colorectal adenomas and cancers, many adenomas and some cancers are missed. To
      avoid interval colorectal cancer, the adenoma miss rate of colonoscopy needs to
      be reduced by improvement of colonoscopy technique and imaging capability. We
      aimed to compare the adenoma miss rates of full-spectrum endoscopy colonoscopy
      with those of standard forward-viewing colonoscopy. METHODS: We did an
      international, multicentre, randomised trial at three sites in Israel, one site
      in the Netherlands, and two sites in the USA between Feb 1, 2012, and March 31,
      2013. Patients aged 18-70 years referred for colorectal cancer screening, polyp
      surveillance, or diagnostic assessment underwent same-day, back-to-back tandem
      colonoscopy with standard forward-viewing colonoscope and the full-spectrum
      endoscopy colonoscope. The patients were randomly assigned (1:1), via computer
      generated randomisation with block size of 20, to which procedure was done first.
      The endoscopist was masked to group allocation until immediately before the start
      of colonoscopy examinations; patients were not masked. The primary endpoint was
      adenoma miss rates. We did per-protocol analyses. This trial is registered with
      ClinicalTrials.gov, number NCT01549535. FINDINGS: 197 participants were enrolled.
      185 participants were included in the per-protocol analyses: 88 (48%) were
      randomly assigned to receive standard forward-viewing colonoscopy first, and 97
      (52%) to receive full-spectrum endoscopy colonoscopy first. By per-lesion
      analysis, the adenoma miss rate was significantly lower in patients in the full
      spectrum endoscopy group than in those in the standard forward-viewing procedure
      group: five (7%) of 67 vs 20 (41%) of 49 adenomas were missed (p<0.0001).
      Standard forward-viewing colonoscopy missed 20 adenomas in 15 patients; of those,
      three (15%) were advanced adenomas. Full-spectrum endoscopy missed five adenomas
      in five patients in whom an adenoma had already been detected with first-pass
      standard forward-viewing colonoscopy; none of these missed adenomas were
      advanced. One patient was admitted to hospital for colitis detected at
      colonoscopy, whereas five minor adverse events were reported including vomiting,
      diarrhoea, cystitis, gastroenteritis, and bleeding. INTERPRETATION: Full-spectrum
      endoscopy represents a technology advancement for colonoscopy and could improve
      the efficacy of colorectal cancer screening and surveillance. FUNDING:
      EndoChoice.

PMID- 24560455
TI  - Nitrergic neurons during early postnatal development of the prefrontal cortex in
      the rat: histochemical study.
AB  - The presence of nitrergic cells in the prefrontal cortex has been confirmed,
      however little is known about the postnatal development of these cells. Nitrergic
      neurons were studied histochemically by using NADPH-diaphorase staining in the
      prefrontal cortex of male Wistar rats from postnatal day 7-21 (P7-21). Neuronal
      NADPH-diaphorase is a nitric oxide synthase that provides a specific
      histochemical marker for neurons producing nitric oxide (NO). NO acts as a
      neurotransmitter and intracellular signaling molecule in the nervous system. We
      observed in 7 day old rats NADPH-d containing neurons that were intensely
      stained. These neurons were bipolar with a short dendrite with average length of
      23 MUm. During the second postnatal week, the neurons were mainly bipolar and
      were rarely multipolar. By P14 the cells were located primarily in cortical
      layers III-VI. Nitrergic neurons of the 21 day old rats were histochemically
      identified as multipolar cells with long radial extending dendrites. Dendrites of
      neurons in 14 and 21 day old rats were a similar length with an average of 57
      MUm. These results suggest that nitrergic neurons differentiate during a
      relatively short period of time and reach their structural maturity by the end of
      the second week of postnatal development.

PMID- 24560456
TI  - Co-expression of cancer testis antigens and topoisomerase 2-alpha in triple
      negative breast carcinomas.
AB  - Triple negative breast cancers (TNBC) are characterized by aggressive tumor
      biology, lack of targeted treatments and poor prognosis. Anthracyclins were shown
      to induce immunogenic death in target cells, potentially leading to "endogenous"
      vaccination. We comparatively assessed expression of cancer testis antigens (CTA)
      and topoisomerase 2-alpha (TOPO2A), a well defined molecular target of
      anthracyclins, in TNBC fully characterized for basal-like (BL) immunophenotype,
      BL morphology and conventional clinicopathological factors. The study included 83
      patients undergoing surgery between January 2003 and December 2009. Tissue
      sections were stained with CK5/6, CK14, EGFR, Ki-67, TOPO2A, MAGE-A1, MAGE-A10,
      NY-ESO and multi-MAGE-A specific reagents. Of the 83 TNBC, >66.3% had BL
      immunophenotype and 48.2% had BL morphology. MAGE-A1 specific staining was most
      frequently detectable (69.2%), followed by multi-MAGE-A (58%), NY-ESO (27.1%) and
      MAGE-A10 (16%) specific staining. MAGE-A10 expression significantly correlated
      with tumor size (p=0.026). Furthermore, MAGE-A1, MAGE-A10 and multi-MAGE-A
      specific stainings significantly correlated with advanced clinical stage
      (p=0.024, p=0.041, p=0.031, respectively). We found no significant association
      between CTA expression and disease free (DFS) or overall survival (OS). Most
      interestingly, a significant correlation was observed between expression of MAGE
      A10 and NY-ESO and expression of TOPO2A (p=0.005, p=0.013). Expression of defined
      CTA and TOPO2A are significantly correlated in TNBC. Considering the limited
      therapeutic options for TNBC, these findings might suggest novel forms of
      combination therapies that should be further explored. 

PMID- 24560457
TI  - Lysosomal enzymes may cross the blood-brain-barrier by pinocytosis: implications
      for enzyme replacement therapy.
AB  - Here we hypothesized that the water-soluble lysosomal enzymes may cross the blood
      brain-barrier and reach the brain using the mechanism of unspecific fluid-phase
      endocytosis. We also highlight studies that show that, at higher serum
      concentrations, a fraction of these proteins can reach the brain after
      intravenous injection, and we suggest some experiments to study this hypothesis.
      Finally we discuss the implications of this for treatments such as enzyme
      replacement of lysosomal storage disorders. 

PMID- 24560458
TI  - The interplay of T1- and T2-relaxation on T1-weighted MRI of hMSCs induced by Gd
      DOTA-peptides.
AB  - Three Gd-DOTA-peptide complexes with different peptide sequence are synthesized
      and used as T1 contrast agent to label human mesenchymal stem cells (hMSCs) for
      magnetic resonance imaging study. The peptides include a universal cell
      penetrating peptide TAT, a linear MSC-specific peptide EM7, and a cyclic MSC
      specific peptide CC9. A significant difference in labeling efficacy is observed
      between the Gd-DOTA-peptides as well as a control Dotarem. All Gd-DOTA-peptides
      as well as Dotarem induce significant increase in T1 relaxation rate which is in
      favor of T1-weighted MR imaging. Gd-DOTA-CC9 yields the maximum labeling efficacy
      but poor T1 contrast enhancement. Gd-DOTA-EM7 yields the minimum labeling
      efficacy but better T1 contrast enhancement. Gd-DOTA-TAT yields a similar
      labeling efficacy as Gd-DOTA-CC9 and similar T1 contrast enhancement as Gd-DOTA
      EM7. The underlying mechanism that governs T1 contrast enhancement effect is
      discussed. Our results suggest that T1 contrast enhancement induced by Gd-DOTA
      peptides depends not only on the introduced cellular Gd content, but more
      importantly on the effect that Gd-DOTA-peptides exert on the T1-relaxation and T2
      relaxation processes/rates. Both T1 and particularly T2 relaxation rate have to
      be taken into account to interpret T1 contrast enhancement. In addition, the
      interpretation has to be based on cellular instead of aqueous longitudinal and
      transverse relaxivities of Gd-DOTA-peptides.

PMID- 24560460
TI  - Enhanced ex vivo expansion of adult mesenchymal stem cells by fetal mesenchymal
      stem cell ECM.
AB  - Large-scale expansion of highly functional adult human mesenchymal stem cells
      (aMSCs) remains technologically challenging as aMSCs lose self renewal capacity
      and multipotency during traditional long-term culture and their quality/quantity
      declines with donor age and disease. Identification of culture conditions
      enabling prolonged expansion and rejuvenation would have dramatic impact in
      regenerative medicine. aMSC-derived decellularized extracellular matrix (ECM) has
      been shown to provide such microenvironment which promotes MSC self renewal and
      "stemness". Since previous studies have demonstrated superior proliferation and
      osteogenic potential of human fetal MSCs (fMSCs), we hypothesize that their ECM
      may promote expansion of clinically relevant aMSCs. We demonstrated that aMSCs
      were more proliferative (~ 1.6 *) on fMSC-derived ECM than aMSC-derived ECMs and
      traditional tissue culture wares (TCPS). These aMSCs were smaller and more
      uniform in size (median +/- interquartile range: 15.5 +/- 4.1 MUm versus 17.2 +/-
      5.0 MUm and 15.5 +/- 4.1 MUm for aMSC ECM and TCPS respectively), exhibited the
      necessary biomarker signatures, and stained positive for osteogenic, adipogenic
      and chondrogenic expressions; indications that they maintained multipotency
      during culture. Furthermore, fMSC ECM improved the proliferation (~ 2.2 *), size
      (19.6 +/- 11.9 MUm vs 30.2 +/- 14.5 MUm) and differentiation potential in late
      passaged aMSCs compared to TCPS. In conclusion, we have established fMSC ECM as a
      promising cell culture platform for ex vivo expansion of aMSCs.

PMID- 24560459
TI  - Controlling chitosan-based encapsulation for protein and vaccine delivery.
AB  - Chitosan-based nano/microencapsulation is under increasing investigation for the
      delivery of drugs, biologics and vaccines. Despite widespread interest, the
      literature lacks a defined methodology to control chitosan particle size and
      drug/protein release kinetics. In this study, the effects of precipitation
      coacervation formulation parameters on chitosan particle size, protein
      encapsulation efficiency and protein release were investigated. Chitosan particle
      sizes, which ranged from 300 nm to 3 MUm, were influenced by chitosan
      concentration, chitosan molecular weight and addition rate of precipitant salt.
      The composition of precipitant salt played a significant role in particle
      formation with upper Hofmeister series salts containing strongly hydrated anions
      yielding particles with a low polydispersity index (PDI) while weaker anions
      resulted in aggregated particles with high PDIs. Sonication power had minimal
      effect on mean particle size, however, it significantly reduced polydispersity.
      Protein loading efficiencies in chitosan nano/microparticles, which ranged from
      14.3% to 99.2%, were inversely related to the hydration strength of precipitant
      salts, protein molecular weight and directly related to the concentration and
      molecular weight of chitosan. Protein release rates increased with particle size
      and were generally inversely related to protein molecular weight. This study
      demonstrates that chitosan nano/microparticles with high protein loading
      efficiencies can be engineered with well-defined sizes and controllable release
      kinetics through manipulation of specific formulation parameters. 

PMID- 24560461
TI  - Mesenchymal stem cell delivery strategies to promote cardiac regeneration
      following ischemic injury.
AB  - Myocardial infarction (MI) is one of the leading causes of mortality worldwide
      and is associated with irreversible cardiomyocyte death and pathological
      remodeling of cardiac tissue. In the past 15 years, several animal models have
      been developed for pre-clinical testing to assess the potential of stem cells for
      functional tissue regeneration and the attenuation of left ventricular
      remodeling. The promising results obtained in terms of improved cardiac function,
      neo-angiogenesis and reduction in infarct size have motivated the initiation of
      clinical trials in humans. Despite the potential, the results of these studies
      have highlighted that the effective delivery and retention of viable cells within
      the heart remain significant challenges that have limited the therapeutic
      efficacy of cell-based therapies for treating the ischemic myocardium. In this
      review, we discuss key elements for designing clinically translatable cell
      delivery approaches to promote myocardial regeneration. Key topics addressed
      include cell selection, with a focus on mesenchymal stem cells derived from the
      bone marrow (bMSCs) and adipose tissue (ASCs), including a discussion of their
      potential mechanisms of action. Natural and synthetic biomaterials that have been
      investigated as injectable cell delivery vehicles for cardiac applications are
      critically reviewed, including an analysis of the role of the biomaterials
      themselves in the therapeutic scheme. 

PMID- 24560462
TI  - Accuracy of osmophobia in the differential diagnosis between migraine and tension
      type headache.
AB  - Our objective was to determine the accuracy parameters of osmophobia in the
      differential diagnosis between migraine and tension-type headache. Migraine or
      tension-type headache patients, diagnosed according to the criteria of the
      International Classification of Headache Disorders-II, were interviewed about
      osmophobia during the crisis and in the period between episodes. We studied 200
      migraine patients and 200 tension-type headache patients. During the crisis,
      osmophobia occurred in 86.0% (172/200) of patients with migraine and 6.0%
      (12/200) of those with tension-type headache. In migraine, osmophobia was
      associated with photophobia and phonophobia (57/172, 33.1%) or with nausea,
      photophobia and phonophobia (92/172, 53.5%) and presented high sensitivity
      (86.0%, 95% CI 80.2-90.3) and specificity (94.0%, 95% CI 89.5-96.7), with low
      percentages of false positives (6.5%, 95% CI 3.6-11.4) and negatives (13.0%, 95%
      CI 8.9-18.4). In the period between attacks, osmophobia was restricted to
      migraine patients (48/200, 24.0%). The areas under ROC curves were: 0.903 +/-
      0.017 to osmophobia during crisis; 0.784 +/- 0.025 between crises; 0.807 +/-
      0.023 to photophobia/phonophobia, and 0.885 +/- 0.017 to pain developed by odors.
      Osmophobia may be a specific marker to differentiate migraine from tension-type
      headache, which suggests its inclusion within the criteria to diagnose migraine.

PMID- 24560463
TI  - Intraoperative fracture during staged total knee reimplantation in the treatment
      of periprosthetic infection.
AB  - Bone stock during knee reimplantation for infection is compromised and may
      contribute to intraoperative fracture. This study aims to describe the prevalence
      of said fractures. A retrospective review was performed of patients who underwent
      a staged TKA reimplantation for a periprosthetic infection. Patients who
      sustained an intraoperative fracture were analyzed. The fracture timing,
      location, and treatment were recorded. Fracture healing, component stability, and
      need for re-revision were noted. Between 1990 and 2010, 894 reimplantations were
      performed. Twenty-three fractures occurred in 21 patients (2.3%) with mean follow
      up of 56 months (range: 4-122). Thirteen fractures occurred in femora, 7 in
      tibiae, and 3 in patellae. Four occurred during resection, while 19 occurred
      during reimplantation. Observation and wires/cables were the most common
      treatments utilized. At final follow-up, 91% of fractures demonstrated union and
      75% of patients demonstrated stable components. Eight patients (38%) required a
      revision, the majority of which were performed for re-infection. 

PMID- 24560464
TI  - Laparoscopy-assisted transvaginal resection of sigmoid cancer.
AB  - OBJECTIVE: To investigate the feasibility and safety of laparoscopy-assisted
      transvaginal resection of sigmoid cancer. METHODS: From 2009 to 2011 we performed
      21 laparoscopy-assisted transvaginal resections of sigmoid cancers. RESULTS: The
      resected tumours were T1(6), T2(7) and T3(8). The median number of resected lymph
      nodes was 15. Median operative time was 150 min and no conversion to open
      technique was necessary. A total of eighteen patients tolerated a liquid diet 24
      h after surgery. The average VAS pain score (0 = no pain, 10 = unbearable pain)
      was 1.8 after 24 h and 1.1 after 48 h. One patient experienced a postoperative
      ileus, two patients had vaginal spotting with serous flow and three patients
      suffered urinary tract infections. One patient developed a hernia at the
      umbilical trocar site that was operated on. None of the sexually active patients
      reported any differences in sexual activity pre-op and postop on a postoperative
      questionnaire. After a median of 25 (10-41) months of follow-up, all patients are
      alive and well, with no evidence of recurrent disease. CONCLUSION: Laparoscopy
      assisted transvaginal resection of sigmoid cancer is feasible and safe in a
      selected group of patients.

PMID- 24560465
TI  - The association of metabolic syndrome markers with adhesive capsulitis.
AB  - BACKGROUND: Research has associated adhesive capsulitis with diabetes mellitus
      but suggests that glucose-mediated injury may begin before diabetes is diagnosed.
      The period preceding diabetes is often marked by metabolic syndrome. METHODS: We
      investigated the relationship between metabolic syndrome components (insulin
      resistance, hypertension, dyslipidemia, and obesity) and the development of
      adhesive capsulitis using a case-control study. We retrospectively reviewed 150
      consecutive adhesive capsulitis patient charts to determine the prevalence of
      obesity and of medications used for treating metabolic syndrome elements and
      compared these with previously reported nationwide values. RESULTS: The
      prevalence of anti-hyperglycemia medications in the adhesive capsulitis cohort
      was 18.4% (95% confidence interval [CI], 12.9%-25.7%), twice the national rate of
      diagnosed diabetes of 7.6% (95% CI, 6.7%-8.5%). In the 20- to 39-year-old group,
      the prevalence of anti-hyperglycemic medications, 26.3% (95% CI, 11.8%-48.8%),
      was over 10 times the nationwide rate. The overall prevalence of hypertensive
      medication use in the adhesive capsulitis group, 33.1% (95% CI, 25.9%-41.2%), was
      notably higher than the nationwide rate, 21.6% (95% CI, 19.8%-23.4%). In the 40-
      to 64-year-old group, the prevalence of hypertensive medication use, 36.8% (95%
      CI, 28.6%-46.0%), was notably higher than the nationwide rate of 24.5% (95% CI,
      22.2%-27.0%). The prevalence of anti-lipid medications and obesity was similar
      between the groups. CONCLUSIONS: The relationship between adhesive capsulitis and
      metabolic syndrome remains unclear. Our results confirm previous work associating
      hyperglycemia with adhesive capsulitis. We have also shown a possible association
      of hypertension, part of metabolic syndrome and a proinflammatory condition, with
      adhesive capsulitis, which has not been previously described.

PMID- 24560466
TI  - Glenoid perforation does not affect the short-term outcomes of pegged all
      polyethylene implants in total shoulder arthroplasty.
AB  - BACKGROUND: The glenoid vault can be perforated during pegged glenoid preparation
      in total shoulder arthroplasty. The clinical implications of glenoid vault
      perforation, however, are unknown. The purpose of this study was to determine the
      effects of perforation of the glenoid during total shoulder arthroplasty on
      clinical and radiographic outcomes. MATERIALS AND METHODS: Eighteen patients with
      known intraoperative glenoid perforations were prospectively identified and
      compared with 34 patients matched by age, gender, diagnosis, and arm dominance
      during the same period. Patients were evaluated with multiple outcome scores.
      Radiographs were evaluated for glenoid lucency immediately postoperatively and at
      final follow-up. RESULTS: Average follow-up was 28.1 months for the perforated
      group and 31.2 months for the matched controls. Both groups had significant
      improvements in outcome scores postoperatively. American Shoulder and Elbow
      Surgeons scores increased from 39.8 to 91.0 (P < .001) in the perforated group
      and from 36.9 to 82.6 (P < .001) in the control group. Constant scores increased
      from 24.4 to 77.4 (P < .001) in the perforated group and from 36.9 to 75.6 (P <
      .001) in the control group. Ninety-four percent of the perforated group and 80%
      of the matched controls were satisfied or very satisfied with their result (P =
      .896). The presence and number of perforations were not related to the American
      Shoulder and Elbow Surgeons score (P = .549), Constant score (P = .154), or
      radiographic lucency grade (P = .584). CONCLUSIONS: Glenoid perforation during
      pegged glenoid preparation in total shoulder arthroplasty does not seem to have
      an adverse effect on clinical or radiographic outcomes at an average of 2 years
      of follow-up.

PMID- 24560467
TI  - The role of pectoralis major and latissimus dorsi muscles in a biomechanical
      model of massive rotator cuff tear.
AB  - BACKGROUND: Superior migration of the humeral head after massive rotator cuff
      tear (mRCT) is thought to lead to cuff tear arthropathy. Previous biomechanical
      studies have demonstrated the ability of the pectoralis major and latissimus
      dorsi (PM/LD) muscles to resist this migration. This study examined the role of
      PM/LD muscles on glenohumeral joint forces and acromiohumeral contact pressures
      in a mRCT model. METHODS: Six cadaveric shoulders were tested using a custom
      shoulder-testing system. Muscle insertions of the rotator cuff, deltoid, and
      PM/LD were preserved and used for muscle loading. Specimens were tested in 3
      different humeral rotation positions at 0 degrees  abduction and 2 rotation
      positions at 60 degrees  abduction. Testing was performed for intact specimens,
      after supraspinatus removal, and after supraspinatus/infraspinatus/teres minor
      removal. PM/LD were loaded or unloaded to determine their effect. Humeral head
      kinematics, glenohumeral joint forces, and acromiohumeral contact area and
      pressure were measured. RESULTS: For the mRCT condition at 0 degrees  abduction,
      unloading the PM/LD resulted in superior shift of the humeral head.
      Acromiohumeral contact pressures were undetectable when the PM/LD were loaded but
      increased significantly after PM/LD unloading. After mRCT, superior joint forces
      were increased and compressive forces were decreased compared with intact;
      loading the PM/LD resolved these abnormal forces in some testing conditions.
      CONCLUSION: In mRCT, the PM and LD muscles are effective in improving
      glenohumeral kinematics and reducing acromiohumeral pressures. Strengthening or
      neuromuscular training of this musculature, or both, may delay the progression to
      cuff tear arthropathy.

PMID- 24560468
TI  - An anthropometric study of the distal humerus.
AB  - BACKGROUND: The optimal articular shape for distal humeral hemiarthroplasty has
      not been defined because of a paucity of data quantifying the morphology of the
      normal distal humerus. This study defines the osseous anatomy and anatomic
      variability of the distal humerus using 3-dimensional imaging techniques.
      METHODS: Three-dimensional surface models were created from computed tomography
      scans obtained from 50 unpaired human cadaveric elbows. Geometric centers of the
      capitellum and the trochlear groove defined the anatomic flexion-extension axis.
      A coordinate system was created, and the distal humerus was sectioned into 100
      slices along this axis. The C line was defined as the line of best fit connecting
      the geometric centers of each of the slices. RESULTS: The anatomic flexion
      extension axis of the distal humerus was found to be an average of 1 degrees  +/-
      1 degrees  from the C line (range, 0 degrees -3 degrees ) in the coronal plane
      and 2 degrees  +/- 1 degrees  (range, 0 degrees -7 degrees ) in the transverse
      plane. The average trochlear width was 22 +/- 3 mm, and the average trochlear
      height was 18 +/- 2 mm. The mean width of the capitellum was 17 +/- 2 mm; the
      height was 23 +/- 2 mm (P < .001). CONCLUSIONS: The difference in the capitellum
      width and height demonstrates that the capitellum is ellipsoid, not spherical. A
      data bank of humeral dimensions may be used for the development of future distal
      humeral hemiarthroplasty implants. A more anatomic implant may optimize
      kinematics and maximize contact area, thus minimizing contact stresses on the
      native ulna and radius.

PMID- 24560470
TI  - Charles Bonnet syndrome in patient with impaired visual field and good visual
      acuity.

PMID- 24560469
TI  - Anterior shoulder capsular tears in professional baseball players.
AB  - BACKGROUND: Tearing of the anterior capsule of the shoulder is a rare but
      debilitating injury for throwing athletes. However, there is very little in the
      literature to guide its diagnosis and treatment. In this case series, we outline
      our experience with anterior capsular tears of the shoulder in professional
      baseball players. METHODS: Five professional baseball players were diagnosed with
      midsubstance tears of their anterior capsule. A trial of rest and rehabilitation
      failed in all patients, and they eventually underwent surgery. These patients
      were retrospectively reviewed. The presenting symptoms and findings were
      documented, and outcomes were assessed by the player's ability to return to play.
      RESULTS: The mean age was 33.5 years (range, 31-37 years), and all patients
      presented with anterior shoulder pain and the inability to throw. No patient had
      an acute traumatic injury. Magnetic resonance imaging provided the correct
      diagnosis in 4 patients, and the diagnosis was made with diagnostic arthroscopy
      in the fifth. Three underwent arthroscopic repair, and 2 underwent open repair of
      the anterior capsule. Of the 5 players, 4 (80%) returned to their preinjury level
      by a mean of 13.3 months (range, 8-18 months). CONCLUSIONS: Anterior capsular
      tears can occur in older throwing athletes. Surgical repair, whether arthroscopic
      or open, can yield good results in most patients.

PMID- 24560471
TI  - Preganglionic or postganglionic efferent pupillary defect? Clinical versus
      neuroimaging diagnosis.

PMID- 24560472
TI  - Functionality predictors in acquired brain damage.
AB  - INTRODUCTION: Most individuals who have survived an acquired brain injury present
      consequences affecting the sensorimotor, cognitive, affective or behavioural
      components. These deficits affect the proper performance of daily living
      activities. The aim of this study is to identify functional differences between
      individuals with unilateral acquired brain injury using functional independence,
      capacity, and performance of daily activities. METHOD: Descriptive cross
      sectional design with a sample of 58 people, with right-sided injury (n=14 TBI;
      n=15 stroke) or left-sided injury (n = 14 TBI, n = 15 stroke), right handed, and
      with a mean age of 47 years and time since onset of 4 +/- 3.65 years. The
      functional assessment/functional independence measure (FIM/FAM) and the
      International Classification of Functioning (ICF) were used for the study.
      RESULTS: The data showed significant differences (P<.000), and a large size
      effect (dr=0.78) in the cross-sectional estimates, and point to fewer
      restrictions for patients with a lesion on their right side. The major
      differences were in the variables 'speaking' and 'receiving spoken messages' (ICF
      variables), and 'Expression', 'Writing' and 'intelligible speech' (FIM/FAM
      variables). In the linear regression analysis, the results showed that only 4
      FIM/FAM variables, taken together, predict 44% of the ICF variance, which
      measures the ability of the individual, and up to 52% of the ICF, which measures
      the individual's performance. Gait alone predicts a 28% of the variance.
      CONCLUSIONS: It seems that individuals with acquired brain injury in the left
      hemisphere display important differences regarding functional and communication
      variables. The motor aspects are an important prognostic factor in functional
      rehabilitation.

PMID- 24560473
TI  - Impact of a comprehensive stroke centre on the care of patients with acute
      ischaemic stroke due to cervical artery dissection.
AB  - INTRODUCTION: Cervical artery dissection (CAD) is the cause of 2% to 3% of
      ischaemic strokes and 10% to 25% of the ischaemic strokes in young people. Our
      objective is to evaluate whether implementation of a comprehensive stroke centre
      (CSC) improves the diagnosis and modifies the prognosis of patients with acute
      stroke due to CAD. PATIENTS AND METHODS: Retrospective study of a registry of
      consecutive patients with acute stroke due to CAD. They were classified according
      to the period of care at our centre: pre-CSC (October 2004-March 2008, 42 months)
      or post-CSC (April 2008-June 2012, 51 months). We compared baseline
      characteristics, methods of diagnosis, treatment and outcome of these patients in
      both periods. RESULTS: Nine patients were diagnosed with CAD in pre-CSC and 26 in
      post-CSC, representing 0.8% and 2.1% of all ischaemic strokes treated in each
      period, respectively. The diagnosis of CAD was made within the first 24 hours in
      42.3% of the patients in post-CSC versus 0% in pre-CSC, by using urgent cerebral
      angiography as a diagnostic test in 46.2% of cases in the second period compared
      to 0% in the first. Both severity of stroke (median NIHSS score 11 vs. 3, P=.014)
      and time to neurological care (265 min vs 148, P=.056) were higher in the post
      CSC period. Endovascular treatment was performed in 34.3%, and all treatments
      were post-CSC. The functional outcome was comparable for both periods.
      CONCLUSIONS: Implementation of a CSC increases the frequency of the diagnosis of
      CAD, as well as the treatment options for these patients in the acute phase of
      stroke.

PMID- 24560474
TI  - Faster increase in body mass index between ages 8 and 13 is associated with risk
      factors for cardiovascular morbidity and mortality.
AB  - BACKGROUND AND AIMS: Excess childhood weight is associated with cardiovascular
      disease (CVD) in adulthood. Whether this is mediated through adult body mass
      index (BMI) and associated risk factors such as metabolic derangements remains
      unclear. The aim was to examine whether childhood BMI velocity (Deltakg m(-2) per
      year) was associated with adult CVD mortality and to examine how adult BMI and
      cardiometabolic risk factors contribute to the association. METHODS AND RESULTS:
      Subjects were 1924 Icelanders born between 1921 and 1935 and living in Reykjavik
      when recruited into a longitudinal study from 1967 to 1991. From ages 8-13 years,
      BMI velocity was calculated to quantify the association between childhood growth
      and adult CVD mortality. Deaths from recruitment to 31 December 2009 were
      extracted from the national register. There were 202 CVD deaths among men and 90
      CVD deaths among women (mean follow-up: 25.9 years). Faster BMI velocity from
      ages 8-13 years was associated with CVD mortality when comparing those in the
      highest versus lowest tertile with corresponding hazard ratio (HR) (95%
      confidence interval (CI)): 1.49 (1.03, 2.15) among men and 2.32 (1.32, 4.08)
      among women after adjustment for mid-life BMI and CVD risk factors. Faster
      childhood BMI velocity was associated with elevated CVD risk factors among men at
      mid-life but these associations were less pronounced among women. CONCLUSION:
      Faster increase in BMI from ages 8-13 years was associated with an increased CVD
      mortality risk. Children with early growth spurts coupled with excess weight gain
      during this transition period from childhood into adolescence should be closely
      monitored to ensure better health in adulthood.

PMID- 24560475
TI  - Estimates of unintended pregnancy rates over the last decade in France as a
      function of contraceptive behaviors.
AB  - OBJECTIVE: We investigate trends in contraceptive behaviors in France and how
      they may have contributed to fluctuations in unintended pregnancy rates over time
      and across subgroups of the population between 2000 and 2010. STUDY DESIGN: Data
      are drawn from three national surveys in France, comprising 4714 women ages 15 to
      49 in 2000, 8613 in 2005 and 5260 in 2010. We used multinomial and simple
      logistic regression models to explore trends in contraceptive behaviors over
      time. We estimated trends in unintended pregnancy rates in relation to population
      shifts in contraceptive behaviors between 2000 and 2010. RESULTS: A third of
      women were not using contraception at the time of the surveys. However, only 2.4%
      in 2000, 3.2% in 2005 and 2.4% in 2010 had an unmet need for contraception
      (p=.002). Among contraceptive users, user-dependent hormonal methods decreased
      from 59% in 2000 to 52% in 2010 (p<.0001), while long-acting reversible methods
      increased from 22% to 24% (p=.04). Changes in contraceptive behaviors resulted in
      fluctuations in unintended pregnancy rates estimated to have risen from 3.16% to
      3.49% between 2000 and 2005, and to have decreased to 3.26% in 2010. Small
      changes in unmet need for contraception exerted the largest effects. CONCLUSION:
      This study indicates that changes in contraceptive behaviors over the past decade
      in France have potentially resulted in significant fluctuations in unintended
      pregnancy rates. Our results also demonstrate that a simple algorithm combining
      contraceptive behaviors and typical-use failure rates may be an acceptable proxy
      for monitoring trends in unintended pregnancies. IMPLICATIONS: This study offers
      a framework towards assessing trends in unintended pregnancies, when data on
      abortions and unintended births are not available. In the context of high
      contraceptive coverage, gaps of use undermine efforts to improve contraceptive
      effectiveness, as small fluctuations in unmet need contribute significantly to
      trends in unintended pregnancy rates.

PMID- 24560477
TI  - Buccal misoprostol plus laminaria for cervical preparation before dilation and
      evacuation at 21-23 weeks of gestation: a randomized controlled trial.
AB  - OBJECTIVE: To describe the effectiveness of buccal misoprostol as an adjunct to
      laminaria for cervical ripening before later second-trimester abortion by
      dilation and evacuation (D&E). METHODS: A randomized, double-blinded, placebo
      controlled trial of 196 women undergoing D&E between 21 and 23 weeks of
      gestation. Subjects had overnight laminaria and 400 mcg buccal misoprostol or
      placebo 3-4 h before the abortion. We used logarithmic transformation of the
      primary outcome--D&E procedure duration--to achieve a normal distribution.
      RESULTS: Mean D&E duration was 1.7 min shorter with misoprostol (p=.02). The
      median duration was 9.7 versus 10.4 min in the misoprostol and placebo groups,
      respectively (p=.09). Cervical dilation was slightly greater with misoprostol
      (median 75 mm vs. 73 mm, p=.04); however, physicians did not find the misoprostol
      D&Es easier to complete. Half of subjects reported severe pain after misoprostol
      vs. 11% with placebo (p<.001). CONCLUSION: Adjuvant buccal misoprostol results in
      slightly shorter D&Es at the cost of more side effects.

PMID- 24560476
TI  - Blockade of tubal patency following transcervical administration of polidocanol
      foam: initial studies in rhesus macaques.
AB  - OBJECTIVE: To demonstrate the feasibility of polidocanol foam (PF) as a
      nonsurgical method of female permanent contraception using a nonhuman primate
      model. STUDY DESIGN: Four groups of adult female rhesus macaques underwent either
      transcervical treatment with 5% PF directly into the uterine cavity, treatment
      with inert (methylcellulose, MF) foam or no treatment followed by removal of the
      reproductive tract for histologic evaluation. Untreated animals were included in
      Group 1 (n=3). Group 2 animals (n=4) were treated once with MF. Group 3 (n=7)
      received a single, and Group 4 (n=5) received multiple monthly treatments with
      PF; in these 2 groups, baseline tubal patency was assessed either
      laparoscopically by chromopertubation (CP) or by hysterosalpingography. RESULTS:
      Group 1 (untreated) and Group 2 (MF) animals had normal tubal histology. In
      contrast, Group 3 and 4 females treated with PF showed evidence of tubal damage.
      In Group 4, bilateral tubal blockade was noted on CP after two (n=2) or three
      (n=3) treatments. Histologic analysis confirmed complete tubal occlusion (loss of
      epithelium, fibrosis) in three of these animals, and one showed significant tubal
      damage localized to the intramural segment. Nontarget (cervix, vagina,
      endometrium, ovary) reproductive tissues were unaffected. While similar tubal
      changes were observed after a single treatment (Group 3), endometrial hemorrhage
      was also noted as an acute change. CONCLUSION: PF is a promising candidate agent
      for nonsurgical permanent female contraception. The histologic features of PF
      occlusion are confined to the intramural portion of the tube. IMPLICATIONS: This
      study in rhesus macaques supports further development of transcervical
      administration of PF as a nonsurgical approach to permanent contraception. A
      nonsurgical method could reduce risks and costs associated with surgical female
      sterilization and increase access to permanent contraception.

PMID- 24560478
TI  - Postpartum contraception utilization among low-income women seeking immunization
      for infants in Mumbai, India.
AB  - OBJECTIVE: The objective was to examine postpartum contraception utilization
      among Indian women seeking immunization for their infants in three low-income
      communities in Mumbai, India. STUDY DESIGN: We conducted a cross-sectional
      questionnaire of low-income postpartum women seeking immunization for their
      infants at three large urban health centers in Mumbai. Contraceptive utilization
      data were collected as part of a larger study focused on the impact of postpartum
      domestic violence on maternal and infant health. Descriptive, bivariate and
      multivariate analyses were conducted to describe and identify predictors of
      postpartum contraceptive utilization. RESULTS: Postpartum women aged 17-45 years
      (N=1049) completed the survey; 44.5% (n=467) reported resuming sexual relations
      with their husbands. Among these women, the majority (65.3%; n=305) reported not
      currently using contraception. In multivariate analyses, women who did not
      discuss postpartum family planning with their husbands, had not used
      contraception previous to the recent birth, and had experienced physical violence
      or forced sex were more likely to not use postpartum contraception (adjusted odds
      ratios=1.47-1.77). Among the 162 women using contraception, the most common time
      to initiation of contraception was 5 weeks postpartum, and the most common method
      used was condoms 77.8% (n=126). CONCLUSION: Contraception nonuse was common among
      urban, low-income postpartum women in India. This study highlights the importance
      of developing interventions to increase use of highly effective contraceptive
      methods postpartum, and that spousal violence and lack of marital communication
      may present barriers to postpartum contraception utilization. Infant immunization
      may represent an opportunity for provision of contraceptives and contraceptive
      counseling. IMPLICATIONS: This original research study is a unique contribution
      to the literature because it presents data regarding the nonuse of postpartum
      contraception among women seeking immunizations for their infants in urban
      centers in a developing country. It also reveals barriers to not using postpartum
      contraception and provides data for future interventions.

PMID- 24560479
TI  - Fear of intrauterine contraception among adolescents in New York City.
AB  - OBJECTIVE: The intrauterine contraceptive device (IUD) is one of the most
      effective contraceptive methods, but it remains underutilized, especially among
      adolescents. Little is known about how adolescents perceive IUDs. The objective
      of this study is to explore urban, minority female adolescents' attitudes and
      beliefs about IUDs and to identify barriers to IUD use. STUDY DESIGN: Qualitative
      semistructured interviews were conducted with 21 adolescents aged 14 to 21 years
      who had heard about the IUD but never used one personally. Participants were
      recruited from two urban school-based health clinics and one community health
      center. Individual interviews were audiotaped and transcribed. Themes were
      identified by two independent researchers through line-by-line analysis of
      interview transcripts. RESULTS: Fear of the IUD predominated. Respondents related
      fears about pain, expulsion, foreign body and the potential for physical harm.
      Common themes in support of the IUD included the IUD's superior efficacy compared
      to other contraceptive methods and the ability to use this method long term.
      Despite identifying IUD benefits, most respondents did not appear to think the
      method would be well suited for them. CONCLUSION: Though the IUD is safe and
      effective for adolescents, we found that urban female adolescents have many
      device-related concerns which must be addressed to make this method more
      acceptable. IMPLICATIONS: Understanding urban, minority adolescents' perspective
      on IUDs and their specific concerns about IUD method use can help clinicians
      provide targeted and relevant contraceptive counseling.

PMID- 24560480
TI  - Permanent contraception: modern approaches justify a new name.

PMID- 24560481
TI  - Simplified follow-up after early medical abortion: 12-month experience of a
      telephone call and self-performed low-sensitivity urine pregnancy test.
AB  - OBJECTIVE: The objective was to determine if simplified follow-up after early
      medical abortion, consisting of a telephone call 2 weeks after the procedure plus
      a self-performed low-sensitivity urine pregnancy (LSUP) test, was successful for
      screening for ongoing pregnancies in the year following its introduction as
      standard service. STUDY DESIGN: A retrospective computerized database review of
      1084 women at a hospital abortion service in Edinburgh, UK, who had a medical
      abortion (<=9 weeks) and went home to expel the pregnancy was performed. Women
      who screened 'positive' at telephone follow-up on the basis of ongoing pregnancy
      symptoms, scant bleeding or LSUP test result were scheduled for an ultrasound.
      The main outcome measures were the proportion of women scheduled for telephone
      follow-up successfully contacted and the proportion of ongoing pregnancies
      detected. RESULTS: A total of 943 women were scheduled for telephone follow-up.
      Ten women presented to the hospital before the time of the follow-up call. Of the
      remaining 933 women, 656 [70%, 95% confidence interval (CI) 67.7-73.2] were
      successfully contacted. Five hundred seventy-three (87%, 95% CI 84.5-89.7) of
      those contacted screened 'negative'; no false negatives occurred. Eighty-three
      (13%, 95% CI 10.2-15.5) screened 'positive,' and of those, three had ongoing
      pregnancies. Of the 277 (30%, 95% CI 26.7-32.7) who were not contacted, two
      ongoing pregnancies occurred. The sensitivity of telephone follow-up with LSUP to
      detect ongoing pregnancy was 100% (95% CI 30.9%-100%), and specificity was 88%
      (95% CI 84.9%-90.1%). The negative predictive value was 100% (95% CI 99.1%-100%),
      and positive predictive value was 3.6% (95% CI 0.9%-10.9%). CONCLUSION: A
      telephone call and LSUP test at 2 weeks are suitable as a standard method of
      follow-up for screening for ongoing pregnancy after early medical abortion.
      IMPLICATIONS STATEMENT: For most women, a routine clinic follow-up after early
      medical abortion (to exclude ongoing pregnancy) can be replaced with a telephone
      call and a self-performed LSUP test at 2 weeks postprocedure.

PMID- 24560482
TI  - The safety, efficacy and acceptability of task sharing tubal sterilization to
      midlevel providers: a systematic review.
AB  - BACKGROUND: Task sharing is an important strategy for increasing access to
      modern, effective contraception for women and reducing unmet need for family
      planning. OBJECTIVE: The objective was to identify evidence for the safety,
      efficacy or acceptability of task sharing tubal sterilization to midlevel
      providers. SEARCH STRATEGY: We searched PubMed, Cochrane and Popline for articles
      in all languages using the following key words: task sharing, tubal
      sterilization, midlevel providers, task shifting. SELECTION CRITERIA: All studies
      reporting on any measure of safety, efficacy or acceptability of tubal
      sterilization performed by any cadre of midlevel providers. DATA COLLECTION AND
      ANALYSIS: Data were independently abstracted by two authors and graded using the
      United States Preventive Services Task Force rating for evidence quality.
      Heterogeneity of outcome measures precluded a meta-analysis. MAIN RESULTS: Nine
      studies of fair to poor quality reported on safety and acceptability outcomes.
      Generalizability of findings is limited by inadequate sample size and lack of
      statistical comparisons. No study reported on long-term efficacy outcomes.
      CONCLUSIONS: Well-designed clinical trials, of adequate sample size, are urgently
      needed to establish the safety, efficacy and acceptability of task sharing tubal
      sterilization to midlevel providers.

PMID- 24560483
TI  - Can ultrasound predict IUD expulsion after medical abortion?
AB  - OBJECTIVES: Our randomized trial compared early and delayed intrauterine device
      (IUD) insertion following medical abortion. In this planned substudy, we explore
      if endometrial thickness and initial IUD position were associated with IUD
      expulsion. We also describe IUD movement within the uterus during the 6 months
      after insertion. STUDY DESIGN: We recruited women undergoing medical abortion and
      choosing the copper IUD for contraception (n=156). Participants were randomly
      assigned to early insertion 1 week after mifepristone or delayed insertion 4-6
      weeks later. We measured endometrial thickness by transvaginal sonogram 1 week
      after abortion and IUD distance from the fundal aspect of the endometrial cavity
      three times: at insertion, 6-8 weeks later and at 6 months. RESULTS: We analyzed
      endometrial thickness in 113 women, baseline IUD position in 114 women and IUD
      movement in 65 women. Women who expelled IUDs (n=15) had slightly thicker
      endometria (p=.007) and slightly lower baseline IUD positions (p=.03) than those
      who retained IUDs, but no clear cutoffs emerged in the receiver operating
      characteristic curve analysis. Retained IUDs commonly moved up and down
      throughout the 6 months (from 14 mm towards the fundus to 32 mm towards the
      cervix). Overall, retained IUDs moved a median of 2mm towards the cervix between
      insertion and exit (p<.0001). CONCLUSIONS: After medical abortion, the risk of
      IUD expulsion increases with thicker endometria and lower baseline position.
      Since no clear cutoffs emerged in the analysis and expulsion remained uncommon
      even with thicker endometria, we do not recommend restricting IUD insertion based
      on ultrasound data. IMPLICATION: Copper T IUDs often move within the uterus
      without expelling. Expulsion is uncommon, and we do not recommend restricting IUD
      insertion based on ultrasound data.

PMID- 24560484
TI  - Biochemical and nutritional markers and antioxidant activity in metabolic
      syndrome.
AB  - BACKGROUND AND OBJECTIVES: 1) Nutritional assessment of the diet followed by
      patients with metabolic syndrome, and 2) biochemical analysis of the oxidation
      reduction level in patients with metabolic syndrome. MATERIAL AND METHODS: A
      cross-sectional study was conducted in patients with metabolic syndrome in
      Murcia. Fifty-three patients, 33 with and 20 without (control group) metabolic
      syndrome, were selected. The intervention consisted of completion of a recall
      survey and a test to nutritionally assess dietary intake. Anthropometric and
      laboratory variables, including those related to antioxidant activity, were also
      tested. RESULTS: Antioxidant activity was within normal limits in both groups
      (1.7 +/- 0.2 mmol/L in the control group and 1.8 +/- 0.1 mmol/L in the metabolic
      syndrome group) (NS). Superoxide dismutase levels were not significantly
      different between the groups. Mean glutathione reductase levels (U/L) were higher
      in the control group as compared to patients with metabolic syndrome (P<.05). As
      regards oxidative stress biomarkers, mean isoprostane levels were higher in the
      control group (4.9 +/- 6.2 ng/mL) than in metabolic syndrome patients (3.5 +/-
      3.9 ng/mL) (P<.05). Oxidized LDL values tended to be higher in metabolic syndrome
      patients (96 +/- 23.2U/L) as compared to the control group (86.2 +/- 17.3 U/L),
      but differences were not significant. CONCLUSIONS: There is a trend to a poorer
      nutritional and biochemical profile in patients with metabolic syndrome, who also
      tend to have a greater degree of oxidative stress.

PMID- 24560485
TI  - [The different types of therapeutic plasma are equivalent?].
AB  - In France, three varieties of therapeutic plasma are being processed, distributed
      and delivered, currently; however, many more varieties are in use worldwide,
      which go by the property of labile blood component or plasma derived medicines.
      For one type of component (one given name), several devices and bags and so on
      are used to concur to its process, which makes that one type of therapeutic
      plasma may significantly differ from one production setting to one other. This
      may affect (more or less) the component properties as well as the possibly
      reported adverse events. This review aims thus, firstly at stressing on the
      difficulty in comparing data obtained in different contexts, and secondly at
      making the point on future directions to process therapeutic plasma. 

PMID- 24560486
TI  - Effective use of naloxone among people who inject drugs in Kyrgyzstan and
      Tajikistan using pharmacy- and community-based distribution approaches.
AB  - BACKGROUND: Opioid overdose (OD) is a major cause of mortality among people who
      inject drugs (PWID) in Central Asia, and distribution of naloxone, an opioid
      antagonist, can effectively prevent these deaths. However, little is known about
      the use and wastage of distributed naloxone ampoules. Having reliable data on
      wastage rates is critical for accurately calculating the health impact of
      naloxone distribution projects targeting PWID. METHODS: In 2011, Population
      Services International (PSI) launched two pilot naloxone distribution programs in
      Kyrgyzstan (pharmacy-based approach) and Tajikistan (community-based approach).
      PWID were trained on OD prevention and naloxone use. Upon returning for more
      ampoules, the PWID completed a brief survey on their OD experience and naloxone
      use. 158 respondents in Kyrgyzstan and 59 in Tajikistan completed the
      questionnaire. Usage and wastage rates were calculated based on responses. A four
      year model wastage rate that takes into account the shelf life of naloxone for
      both countries was then calculated. RESULTS: 51.3% of respondents in Kyrgyzstan
      and 91.5% in Tajikistan reported having ever experienced an OD. 82.9% of
      respondents in Kyrgyzstan and all respondents in Tajikistan had ever witnessed an
      OD. Out of these PWID who experienced or witnessed OD, 81.5% in Kyrgyzstan and
      59.3% in Tajikistan reported having been injected with naloxone, and 83.2% in
      Kyrgyzstan and 50.9% in Tajikistan reported injecting another individual with
      naloxone. Of ampoules received, 46.5% in Kyrgyzstan and 78.1% in Tajikistan were
      used. In both countries, 3.1% of these ampoules were wasted. The four-year model
      wastage rates for Kyrgyzstan and Tajikistan were found to be 13.8% and 3.9%
      respectively. CONCLUSION: Findings indicate that a high proportion of naloxone
      distributed to PWID is used in actual OD incidents, with low wastage rates in
      both countries. Expanding these distribution models can potentially create more
      positive health outcomes for PWID in Central Asia.

PMID- 24560487
TI  - Biweekly irinotecan plus cisplatin versus irinotecan alone as second-line
      treatment for advanced gastric cancer: a randomised phase III trial (TCOG GI
      0801/BIRIP trial).
AB  - PURPOSE: We compared biweekly irinotecan plus cisplatin (BIRIP) with irinotecan
      alone as the second-line chemotherapy (SLC) for advanced gastric cancer (AGC).
      METHODS: Patients with metastatic or recurrent gastric cancer refractory to S-1
      based first-line chemotherapy were randomly assigned to receive BIRIP (irinotecan
      60mg/m(2) plus cisplatin 30mg/m(2), every 2weeks) or irinotecan alone (irinotecan
      150mg/m(2), every 2weeks). The primary end-point was to show the superiority of
      BIRIP to irinotecan in terms of progression free survival (PFS). RESULTS: 130
      patients were enrolled. PFS was significantly longer in the BIRIP group
      (3.8months [95% confidence interval (CI) 3.0-4.7]) than in the irinotecan group
      (2.8months [2.1-3.3]; hazard ratio 0.68, 95% CI 0.47-0.98; P=0.0398). Median
      overall survival was 10.7months in the BIRIP group and 10.1months in the
      irinotecan group (HR 1.00, 95% CI 0.69-1.44, P=0.9823). The objective response
      rate was 22% in the BIRIP group and 16% in the irinotecan group (P=0.4975).
      However, the disease control rate was significantly better in the BIRIP group
      (75%) than in the irinotecan group (54%, P=0.0162). The incidences of grade 3 or
      worse adverse events did not differ between the two groups. Any grade elevation
      of serum creatinine was more common in the BIRIP group (25% versus 8%, P=0.009),
      but any grade diarrhoea (17% versus 42%, P=0.002) was more common in the
      irinotecan group. CONCLUSION: BIRIP significantly prolonged PFS as compared with
      irinotecan alone and was tolerated as SLC, but did not demonstrate the survival
      benefit in this trial.

PMID- 24560488
TI  - Compliance with guidelines and correlation with outcome in patients with advanced
      germ-cell tumours.
AB  - PURPOSE: To evaluate prior compliance with guidelines in patients treated with
      salvage chemotherapy for advanced germ-cell tumours (GCT). PATIENTS AND METHODS:
      Data concerning the initial management of patients requiring salvage chemotherapy
      for GCT at Institut Gustave Roussy between 2000 and 2010 were obtained and
      correlated with recommendations for treatment. Criteria of non-compliance were
      defined based on guidelines. Compliance with guidelines, predictive factors for
      non-compliance and the impact on outcome were analysed. RESULTS: Among 82
      patients treated in the salvage setting, guidelines to initial treatment were
      followed in only 41 cases (50%). The most common non-compliance criteria were non
      adherence to the planned dose (16%), an inappropriate interval between first-line
      chemotherapy cycles (16%), the lack of post-chemotherapy surgery (16%) and a long
      interval to post-chemotherapy surgery (48%). Compliance with standard care was
      better in cancer centres than in other hospitals (private or public) (Odd Ratio
      (OR): 6.9, P = 0.001). A poor-risk status according to the International Germ
      Cell Cancer Collaborative Group (IGCCCG) was also predictive of compliance in
      univariate but not in multivariate analysis. No significant difference in outcome
      after salvage chemotherapy was observed. Patients relapsing after non-compliant
      first-line therapy tended to be more easily salvaged, which is consistent with
      the fact that their initial treatment was inadequate. Some of these relapses were
      therefore probably not due to true biologically refractory disease. CONCLUSION:
      Guidelines for first-line treatment are adhered to in only half the patients
      requiring salvage chemotherapy. As the only predictive factor for non-compliance
      was the treating centre, centralisation of patients with GCT in well-trained
      hospitals should be recommended.

PMID- 24560489
TI  - The prevalence of human papillomavirus in colorectal adenomas and
      adenocarcinomas: a systematic review and meta-analysis.
AB  - BACKGROUND: The role of human papillomavirus (HPV) in colorectal cancer has been
      widely studied with conflicting results. We performed a systematic review and a
      meta-analysis to estimate the prevalence of HPV in colorectal adenocarcinomas and
      adenomas, and test the potential association. METHODS: The pooled HPV prevalence
      was estimated using a random effects model and the I(2) statistic was used to
      describe the amount of heterogeneity. Potential sources of heterogeneity were
      evaluated by meta-regression and stratified analyses. For the studies on
      adenocarcinomas including control tissue, random effects estimates of odds ratios
      (ORs) and 95% confidence intervals (CIs) were calculated. RESULTS: Thirty-seven
      studies were included. Among the 2630 adenocarcinomas, the pooled HPV prevalence
      was 11.2% (95% CI, 4.9-19.6%) with substantial between-study heterogeneity
      (I(2)=97.2%). The HPV prevalence varied by geographical region with highest
      prevalence in South America (45.1%, 95% CI, 21.9-69.4%), Asia (39.2%, 95% CI,
      20.3-60.0%) and the Middle East (32.2%, 95% CI, 1.1-79.3%), and by detection
      method with the highest HPV prevalence in PCR-based studies. In the eight case
      control studies, the pooled HPV prevalence was 36.8% (95% CI, 21.3-53.8%) in
      adenocarcinomas and 1.6% (95% CI, 0.0-9.6%) in controls giving an OR of 6.0 (95%
      CI, 2.0-17.9%) for the association between HPV and colorectal cancer. Among the
      415 adenomas, the pooled HPV prevalence was 5.1% (95% CI, 0.0-17.8%; I(2)=93.7%).
      CONCLUSIONS: HPV may be associated with a subset of colorectal cancers. Future
      large-scale multicenter case-control studies with data on risk factors such as
      lifestyle and sexual behaviour are needed.

PMID- 24560490
TI  - Clinical management of cranio-vertebral instability after whiplash, when
      guidelines should be adapted: a case report.
AB  - Cranio-vertebral instability (CVI) due to loss of bony or ligamentous integrity
      is one of the sequelae that may result after a whiplash mechanism injury. Due to
      the lack of specificity of diagnostic tests, this condition is often missed and
      the default classification of whiplash associated disorder (WAD) is assigned.
      This case report describes a 14-year-old boy who was initially classified with
      WAD II after a rugby injury. He was initially advised to return to usual
      activity, a treatment recommended in clinical guidelines for WAD. Due to an
      adverse response to this course of action, his primary carer, a musculoskeletal
      physiotherapist, continued with facilitating secondary referrals that ultimately
      led to a specialist physiotherapist. The patient was subsequently found to have
      CVI arising from a loss of bony integrity due to spina bifida atlanto, a
      congenital defect in the atlas. Treatment thus was immobilization and
      stabilization, a treatment usually recommended against in WAD guidelines. The
      patient recovered and within 8 weeks had returned to school and non-contact
      sports. This case study, therefore, presents a scenario where current clinical
      guidelines for whiplash could not be followed, and where pursuing clinical
      reasoning led to accurate diagnosis as well as safe and tailored management. The
      case also highlights the integrated roles that primary and specialist health
      professionals should play in the clinical pathway of care after WAD. As a result,
      an expanded diagnostic algorithm and pathway of care for WAD are proposed. 

PMID- 24560491
TI  - Nursing problem-based learning activity: song writing and singing.
AB  - The function of song is not only to deliver individual's messages, but also to
      serve as a learning approach to facilitate students' learning. To observe the
      effectiveness of songs in facilitating students' learning, a Problem-based
      Learning (PBL) class with twenty students was divided into four groups with five
      students per group. Each group was asked to write a song based on two given
      scenarios, to sing the song out loud, and to participate in a follow-up focus
      group interview afterwards. The four songs reflected the students' understanding
      of academic knowledge and their perspectives toward the protagonists in the
      presented scenarios. Two songs are presented in this paper to demonstrate how the
      approach was carried out in the nursing PBL class. This paper aims to show the
      implication of song writing and singing in PBL and shed some light on teaching
      and learning. 

PMID- 24560492
TI  - Safety of an intravenous formulation of lamotrigine.
AB  - PURPOSE: Intravenous (IV) formulations are useful when treating patients where
      oral administration is not possible and to study certain pharmacokinetic
      parameters such as bioavailability. We developed a stable-labeled IV formulation
      of lamotrigine (LTG) for studying pharmacokinetics in epilepsy patients. METHODS:
      Stable-labeled IV LTG was given to 20 persons with epilepsy (6 men; 14 women)
      with a mean age of 34.8 years (SD 11.7). A 50mg dose of LTG (stable labeled) was
      given intravenously and replaced 50mg of the regular morning oral dose of LTG
      (unlabeled, commercially available formulation). RESULTS: No significant changes
      in blood pressure, heart rate, or adverse events including rash were attributed
      to administration of a 50-mg dose of the intravenous LTG formulation. CONCLUSION:
      Our results show that LTG base that is complexed with 2-hydroxypropyl-beta
      cyclodextrin and stable-labeled can be given safely as a tracer replacement dose.

PMID- 24560493
TI  - Clinical relevance of galectin-1 expression in non-small cell lung cancer
      patients.
AB  - BACKGROUND: Identification of biomarkers in lung cancer, a leading cause of
      cancer-related mortality, has a meaningful clinical relevance in the quest of
      novel prognostic factors and therapeutic targets. The glycan-binding protein
      galectin-1 (Gal-1) modulates tumor progression by mediating cell-cell and cell
      extracellular matrix interactions, as well as angiogenesis and tumor immune
      escape. Previous works reported the expression of Gal-1 in lung cancer, although
      its clinical significance remains uncertain. OBJECTIVE: To assess the
      clinicopathologic relevance and prognostic value of Gal-1 expression in a cohort
      of 103 Stage I-III non-small cell lung cancer (NSCLC) patients. METHODS: Gal-1
      expression was determined by immunohistochemistry in tumor tissue samples. The
      percentage of immunoreactive tumor cells and stroma, as well as the presence of
      blood vessels with positively stained endothelium in the tumor and surrounding
      normal tissue, were recorded. Results were correlated with the clinicopathologic
      factors of the patients (Spearman's rank correlation coefficient, chi-square
      test) and overall survival by univariate (Kaplan Meier) and multivariate analyses
      (Cox regression hazard model). RESULTS: We did not observe significant
      associations between Gal-1 expression and relevant clinicopathologic features at
      diagnosis of NSCLC. However, Kaplan Meier analysis revealed a significant
      association between Gal-1 expression and overall survival, when Gal-1 expression
      was analyzed on tumor cells alone ("tumor cell percentage") or when an integrated
      score accounting for tumor cell as well as stromal expression of Gal-1 ("total
      score") was assessed. Patients showing high Gal-1 expression evidenced a poorer
      clinical outcome. Furthermore, "total score" remained significantly associated
      with survival by multivariate Cox regression analysis in the whole cohort of
      patients, even when controlling for the classical predictors and prognostic
      factors of NSCLC. CONCLUSION: We conclude that Gal-1 expression may be a useful
      biomarker for better prediction of the clinical outcome and management of NSCLC
      patients.

PMID- 24560494
TI  - The interplay of human chorionic gonadotropin (hCG) with basic fibroblast growth
      factor and adipokines on angiogenesis in vitro.
AB  - INTRODUCTION: Human chorionic gonadotropin (hCG) is suggested to regulate
      placental angiogenesis, however, its role is incompletely understood. hCG may
      directly stimulate angiogenesis or influence the effect of other angiogenic
      factors. We examined the effect of hCG and the interplay of hCG with basic
      fibroblast growth factor (bFGF) and with various adipokines on proliferation of
      vascular endothelial cells in vitro. METHODS: Human umbilical vein endothelial
      cells (HUVEC) were incubated for 2 days with combinations of hCG, bFGF, leptin,
      resistin, adiponectin, IL6 and TNFalpha. Incorporation of radiolabelled thymidine
      was used to assess cell proliferation. Immunofluorescence and flow cytometry were
      used to examine activation of p44/42 mitogen-activated kinase (MAPK). RESULTS:
      hCG induced proliferation of HUVEC alone and in combination with bFGF. Cells
      exposed to both hCG and bFGF displayed increased activation of p44/42 MAPK as
      compared to hCG or bFGF alone. Increased HUVEC proliferation was observed in the
      presence of increasing concentrations of leptin, resistin, adiponectin, and IL6,
      whereas HUVEC proliferation decreased in the presence of TNFalpha. hCG in
      combination with leptin, resistin, adiponectin or IL6 stimulated HUVEC
      proliferation beyond the effect of hCG alone. DISCUSSION: An interplay of hCG
      with adipose tissue-derived factors with angiogenic properties is plausible.
      Thus, maternal obesity may affect placental angiogenesis in pregnancy.
      CONCLUSIONS: hCG may directly stimulate angiogenesis. Also, hCG may indirectly
      stimulate angiogenesis through interplay with bFGF and adipokines.

PMID- 24560495
TI  - Umbilical cord length in singleton gestations: a Finnish population-based
      retrospective register study.
AB  - INTRODUCTION: Many complications of pregnancy and delivery are associated with
      umbilical cord length. It is important to examine the variation in length, in
      order to identify normal and abnormal conditions. Moreover, the factors
      influencing cord growth and development are not precisely known. OBJECTIVE: The
      main objectives were to provide updated reference charts for umbilical cord
      length in singleton pregnancies and to evaluate potential factors affecting cord
      length. METHODS: Birth register data of 47,284 singleton pregnant women
      delivering in Kuopio University Hospital, Finland was collected prospectively.
      Gender-specific centile charts for cord length from 22 to 44 gestational weeks
      were obtained using generalized additive models for location, scale, and shape
      (GAMLSS). Gestational, fetal, and maternal factors were studied for their
      potential influence on cord length with single variable analysis and stepwise
      multiple linear regression analysis. RESULTS: Cord length increased according to
      gestational age, while the growth decelerated post-term. Birth weight, placental
      weight, pregravid maternal body mass index, parity, and maternal age correlated
      to cord length. Gestational diabetes and previous miscarriages were associated
      with longer cords, while female gender and placental abruption were associated
      with shorter cords. DISCUSSION AND CONCLUSIONS: Girls had shorter cords
      throughout gestation although there was substantial variation in length in both
      genders. Cord length associated significantly with birth weight, placental
      weight, and gestational age. Significantly shorter cords were found in women with
      placental abruption. This important finding requires further investigation.

PMID- 24560496
TI  - [Rhombencephalosynapsis, a rare congenital abnormality easy to diagnose].

PMID- 24560497
TI  - [Morbidity and mortality in newborns at the limit of viability in Spain: a
      population-based study].
AB  - INTRODUCTION: Perinatal care in extremely immature newborns is a clinical and
      ethical problem of great importance for professionals and families, and requires
      that the available information on the chances of child survival is of the highest
      quality. The aim of this study was to determine the specific rates of survival at
      hospital discharge, and survival without major morbidity in newborns with a
      gestation age (GA) <= 26 weeks in Spain. PATIENTS AND METHODS: We included live
      newborns <= 26 weeks admitted to the collaborating centers of the SEN1500 network
      (2004-2010). Out born patients, infants who died in delivery room, and those with
      congenital anomalies incompatible with life were excluded. RESULTS: A total of
      3,236 patients were included. GA specific survival was 12.5, 13.1, 36.9, 55.7,
      and 71.9% at 22, 23, 24, 25, and 26 weeks of GA, respectively. Survival without
      severe intracranial hemorrhage, periventricular leukomalacia, bronchopulmonary
      dysplasia, and/or retinopathy of prematurity was 1.5, 9.5, 19.0, and 29.9% at 23,
      24, 25 and 26 weeks GA, respectively. CONCLUSIONS: Survival without major
      morbidity in infants less than 23 weeks GA is exceptional, and scarce in newborns
      with 23 and 24 weeks GA. Infants >= 25 weeks GA have reasonable chances of
      survival and, in the absence of major malformations or other relevant
      complications, should be offered active resuscitation and intensive care. The
      continuous updating of the results of individual centers is of utmost importance,
      as well as their comparison with the reference population-based results.

PMID- 24560498
TI  - [Status of pediatric hospital medicine in Spain: a report by the Spanish
      Pediatric Hospital Medicine Society (SEPHO)].
AB  - Few reports are available on the status of pediatric hospital medicine in Spain.
      This has prompted the Spanish Society of Hospital Pediatrics (SEPHO) to conduct a
      study to determine the status of pediatric hospital care received. Data released
      by the Ministry of Health, the National Institute of Statistics have been used in
      the study, and an analysis was made of the results of a computerized survey
      designed and developed by SEPHO and available on the Internet for completion from
      November 2011 to December 2012 among Spanish hospitals. The results of this
      survey are part of the beginning of our journey as an association, and the
      current status of child and family welfare during hospitalization needs to be
      determined in order to consider and, where appropriate, make recommendations for
      improvement and standardization of care. The study, still unpublished, is to
      determine the state of pediatric hospital care as seen and analyzed from the
      perspective of the professionals directly involved in pediatric general hospital
      care. We included hospitals of different size and complexity of care. The aim of
      this report is to present the results of the survey and relate it to demographic
      and health care data from official sources.

PMID- 24560499
TI  - Preparation of a micropatterned rigid-soft composite substrate for probing
      cellular rigidity sensing.
AB  - Substrate rigidity has been recognized as an important property that affects
      cellular physiology and functions. While the phenomenon has been well recognized,
      understanding the underlying mechanism may be greatly facilitated by creating a
      microenvironment with designed rigidity patterns. This chapter describes in
      detail an optimized method for preparing substrates with micropatterned rigidity,
      taking advantage of the ability to dehydrate polyacrylamide gels for
      micropatterning with photolithography, and subsequently rehydrate the gel to
      regain the original elastic state. While a wide range of micropatterns may be
      prepared, typical composite substrates consist of micron-sized islands of rigid
      photoresist grafted on the surface of polyacrylamide hydrogels of defined
      rigidity. These islands are displaced by cellular traction forces, for a distance
      determined by the size of the island, the rigidity of the underlying hydrogel,
      and the magnitude of traction forces. Domains of rigidity may be created using
      this composite material to allow systematic investigations of rigidity sensing
      and durotaxis. 

PMID- 24560500
TI  - Patterned hydrogels for simplified measurement of cell traction forces.
AB  - To understand mechanobiology, a quantitative understanding of how cells interact
      mechanically with their environment is needed. Cell mechanics is important to
      study as they play a role in cell behaviors ranging from cell signaling to
      epithelial to mesenchymal transition in physiological processes such as
      development and cancer. To study changes in cell contractile behavior, numerous
      quantitative measurement techniques have been developed based on the measurement
      of deformations of a substrate from an initial state. Herein, we present details
      on a technique we have developed for the measurements of 2D cellular traction
      forces with the goal of facilitating adaptation of this technique by other
      investigators. This technique is flexible in that it utilizes well-studied
      methods for microcontact printing and fabrication of polyacrylamide hydrogels to
      generate regular arrays of patterns that can be transferred onto the hydrogels.
      From the deformation of the arrays, an automated algorithm can be used to
      quantitatively determine the traction forces exerted by the cells onto the
      adhesion points. The simplicity and flexibility of this technique make it a
      useful contribution to our toolbox for measurement of cell traction forces. 

PMID- 24560501
TI  - Micropatterning hydroxy-PAAm hydrogels and Sylgard 184 silicone elastomers with
      tunable elastic moduli.
AB  - This protocol describes a simple method to deposit protein micropatterns over a
      wide range of culture substrate stiffness (three orders of magnitude) by using
      two complementary polymeric substrates. In the first part, we introduce a novel
      polyacrylamide hydrogel, called hydroxy-polyacrylamide (PAAm), that permits to
      surmount the intrinsically nonadhesive properties of polyacrylamide with minimal
      requirements in cost or expertize. We present a protocol for tuning easily the
      rigidity of "soft" hydroxy-PAAm hydrogels between ~0.5 and 50 kPa and a
      micropatterning method to locally deposit protein micropatterns on these
      hydrogels. In a second part, we describe a protocol for tuning the rigidity of
      "stiff" silicone elastomers between ~100 and 1000 kPa and printing efficiently
      proteins from the extracellular matrix. Finally, we investigate the effect of the
      matrix rigidity on the nucleus of primary endothelial cells by tuning the
      rigidity of both polymeric substrates. We envision that the complementarity of
      these two polymeric substrates, combined with an efficient microprinting
      technique, can be further developed in the future as a powerful mechanobiology
      platform to investigate in vitro the effect of mechanotransduction cues on
      cellular functions, gene expression, and stem cell differentiation.

PMID- 24560503
TI  - Micropatterning on micropost arrays.
AB  - Micropatterning of cells can be used in combination with microposts to control
      cell shape or cell-to-cell interaction while measuring cellular forces. The
      protocols in this chapter describe how to make SU8 masters for stamps and
      microposts, how to use soft lithography to replicate these structures in
      polydimethylsiloxane, and how to functionalize the surface of the microposts for
      cell attachment. 

PMID- 24560502
TI  - The facile generation of two-dimensional stiffness maps in durotactic cell
      platforms through thickness projections of three-dimensional submerged
      topography.
AB  - An innovative platform that aims to facilitate studies of how adherent cells
      migrate in response to rigidity gradients or durotaxis has been developed. Soft
      polyacrylamide gel-based cell culture scaffolds are used to fabricate flat
      surfaces containing elasticity gradients through changes in the underlying
      patterned features. Moreover, this inert gel surface supports long-term cell
      viability and offers a tunable stiffness. By manipulating the thickness of the
      gel substrate through the embedded patterns, this system is also capable of
      directing collective cell patterning. 

PMID- 24560504
TI  - Development of micropatterned cell-sensing surfaces.
AB  - Microfabricated surfaces have been widely utilized for defining adhesion of
      single cells or groups of cells of various kinds. Beyond simple control of cell
      attachment, it is often important to monitor the molecules released by cells. Co
      immobilizing miniature sensors alongside cells enables more sensitive detection
      of secreted factors and may allow for such detection to happen within the context
      of local microenvironment. Methods for interfacing cells and sensors are central
      to the notion of local in situ detection of cell function. This chapter describes
      the use of hydrogel photolithography for integrating cells and sensing elements
      on culture surfaces. Two types of micropatterned sensing surfaces are described:
      (1) arrays of microwells for single cell capture that contain antibodies against
      secreted proteins and (2) entrapment of enzymes inside hydrogel microstructures
      for local detection of cell metabolism. In both cases, poly(ethylene glycol)
      hydrogel lithography was employed to control cell attachment, in the second
      approach hydrogel structures also carried enzymes and functioned as sensors. The
      development of robust cell/sensor interfaces has implications for diagnostics,
      tissue engineering, and drug screening. 

PMID- 24560505
TI  - Microfluidic patterning of protein gradients on biomimetic hydrogel substrates.
AB  - This protocol describes a versatile microfluidic method to generate tethered
      protein gradients of virtually any user-defined shape on biomimetic hydrogel
      substrates. It can be applied to test, in a microenvironment of physiologically
      relevant stiffness, how cells respond to graded biomolecular signals, for example
      to elucidate how morphogen proteins affect stem cell fate. The method is based on
      the use of microfluidic flow focusing to rapidly capture in a step-wise manner
      tagged biomolecules via affinity binding on the gel surface. The entire
      patterning process can be performed in <1 h. We illustrate one application of
      this method, namely, the spatial control of mouse embryonic stem cell self
      renewal in response to gradients of the self-renewal-promoting signal leukemia
      inhibitory factor.

PMID- 24560506
TI  - Micropatterning of poly(ethylene glycol) diacrylate hydrogels.
AB  - This protocol describes the techniques to synthesize and fabricate micropatterned
      poly(ethylene glycol) diacrylate-based hydrogels that can be used as substrates
      in cellular studies and tissue engineering scaffolds. These materials provide an
      essentially bioinert background material due to the very low protein adsorption
      characteristics of poly(ethylene glycol), but the materials can be modified with
      covalently grafted peptides, proteins, or other biomolecules of interest to
      impart specific biofunctionality to the material. Further, it is possible to use
      micropatterning technologies to control the localization of such covalent
      grafting of biomolecules to the hydrogel materials, thus spatially controlling
      the cell-material interactions. This protocol presents a relatively simple
      approach for mask-based photolithographic patterning, generally best suited for
      patterning the surface of hydrogel materials for 2D cell studies. A more
      sophisticated technique, two-photon laser scanning lithography, is also
      presented. This technique allows free-form, 3D micropatterning in hydrogels. 

PMID- 24560507
TI  - Curved and folded micropatterns in 3D cell culture and tissue engineering.
AB  - Cells live in a highly curved and folded micropatterned environment within the
      human body. Hence, there is a need to develop engineering paradigms to replicate
      these microenvironments in order to investigate the behavior of cells in vitro,
      as well as to develop bioartificial organs for tissue engineering and
      regenerative medicine. In this chapter, we first motivate the need for such
      micropatterns based on anatomical considerations and then survey methods that can
      be utilized to generate curved and folded micropatterns of relevance to 3D cell
      culture and tissue engineering. The methods surveyed can broadly be divided into
      two classes: top-down approaches inspired by conventional 2D microfabrication and
      bottom-up approaches most notably in the self-assembly of thin patterned films.
      These methods provide proof of concept that the high resolution, precise and
      reproducible patterning of cell and matrix microenvironments in anatomically
      relevant curved and folded geometries is possible. A specific protocol is
      presented to create curved and folded hydrogel micropatterns. 

PMID- 24560508
TI  - Cell migration in confined environments.
AB  - We describe a protocol for measuring the speed of human neutrophils migrating
      through small channels, in conditions of mechanical confinement comparable to
      those experienced by neutrophils migrating through tissues. In such conditions,
      we find that neutrophils move persistently, at constant speed for tens of
      minutes, enabling precise measurements at single cells resolution, for large
      number of cells. The protocol relies on microfluidic devices with small channels
      in which a solution of chemoattractant and a suspension of isolated neutrophils
      are loaded in sequence. The migration of neutrophils can be observed for several
      hours, starting within minutes after loading the neutrophils in the devices. The
      protocol is divided into four main steps: the fabrication of the microfluidic
      devices, the separation of neutrophils from whole blood, the preparation of the
      assay and cell loading, and the analysis of data. We discuss the practical steps
      for the implementation of the migration assays in biology labs, the adaptation of
      the protocols to various cell types, including cancer cells, and the
      supplementary device features required for precise measurements of directionality
      and persistence during migration. 

PMID- 24560509
TI  - Micropatterned porous membranes for combinatorial cell-based assays.
AB  - Here, we describe a protocol for producing micropatterned porous membranes which
      can be used for combinatorial cell-based assays. We use contact printing to
      pattern the surface of a porous filter membrane with a thin layer of
      polydimethylsiloxane (PDMS). This allows the porosity of the filter membrane to
      be altered at selected locations. Cells can be grown on one side of the filter
      membrane, while drugs and reagents can be deposited on the porous areas of the
      other side of the membrane. The reagents can diffuse through the pores of the
      membrane to the cells. The first part of the protocol describes how to design a
      stamp and use it to contact print PDMS. The second part describes how to create
      microprinted membranes for cell-based assays. The method is simple, highly
      customizable, can be performed at the bench, and can be used to perform
      combinatorial or time-dependent cell-based assays. 

PMID- 24560510
TI  - Micropatterning cells on permeable membrane filters.
AB  - Epithelium is abundantly present in the human body as it lines most major organs.
      Therefore, ensuring the proper function of epithelium is pivotal for successfully
      engineering whole organ replacements. An important characteristic of mature
      epithelium is apical-basal polarization which can be obtained using the air
      liquid interface (ALI) culture system. Micropatterning is a widely used
      bioengineering strategy to spatially control the location and organization of
      cells on tissue culture substrates. Micropatterning is therefore an interesting
      method for generating patterned epithelium. Enabling micropatterning of
      epithelial cells however requires micropatterning methods that are designed to
      (i) be compatible with permeable membranes substrates and (ii) allow prolonged
      culture of patterned cells, both of which are required for appropriate epithelial
      apical-basal polarization. Here, we describe a number of methods we have
      developed for generating monoculture as well as coculture of epithelial cells
      that are compatible with ALI culture. 

PMID- 24560511
TI  - Microfabrication of a platform to measure and manipulate the mechanics of
      engineered microtissues.
AB  - Engineered tissues can be used to understand fundamental features of biology,
      develop organotypic in vitro model systems, and as engineered tissue constructs
      for replacing damaged tissue in vivo. However, a key limitation is an inability
      to test the wide range of parameters that might impact the engineered tissue in a
      high-throughput manner and in an environment that mimics the three-dimensional
      (3D) native architecture. We developed a microfabricated platform to generate
      arrays of microtissues embedded within 3D micropatterned matrices.
      Microcantilevers simultaneously constrain microtissue formation and report forces
      generated by the microtissues in real time, opening the possibility to use high
      throughput, low-volume screening for studies on engineered tissues. Thanks to the
      micrometer scale of the microtissues, this platform is also suitable for high
      throughput monitoring of drug-induced effect on architecture and contractility in
      engineered tissues. Moreover, independent variations of the mechanical stiffness
      of the cantilevers and collagen matrix allow the measurement and manipulation of
      the mechanics of the microtissues. Thus, our approach will likely provide
      valuable opportunities to elucidate how biomechanical, electrical, biochemical,
      and genetic/epigenetic cues modulate the formation and maturation of 3D
      engineered tissues. In this chapter, we describe the microfabrication,
      preparation, and experimental use of such microfabricated tissue gauges. 

PMID- 24560512
TI  - Methods for two-dimensional cell confinement.
AB  - Protocols described in this chapter relate to a method to dynamically confine
      cells in two dimensions with various microenvironments. It can be used to impose
      on cells a given height, with an accuracy of less than 100 nm on large surfaces
      (cm(2)). The method is based on the gentle application of a modified glass
      coverslip onto a standard cell culture. Depending on the preparation, this
      confinement slide can impose on the cells a given geometry but also an
      environment of controlled stiffness, controlled adhesion, or a more complex
      environment. An advantage is that the method is compatible with most optical
      microscopy technologies and molecular biology protocols allowing advanced
      analysis of confined cells. In this chapter, we first explain the principle and
      issues of using these slides to confine cells in a controlled geometry and
      describe their fabrication. Finally, we discuss how the nature of the confinement
      slide can vary and provide an alternative method to confine cells with gels of
      controlled rigidity.

PMID- 24560514
TI  - Methods in Cell Biology. Micropatterning in cell biology part C. Preface.

PMID- 24560513
TI  - Benzophenone-based photochemical micropatterning of biomolecules to create model
      substrates and instructive biomaterials.
AB  - The extracellular matrix (ECM) is a dynamic and heterogeneous environment that
      controls many aspects of cell behavior. Not surprisingly, many different
      approaches have focused on creating model substrates that recapitulate the
      biomolecular, topographical, and mechanical properties of the ECM for in vitro
      studies of cell behavior. This chapter details a general, versatile method for
      the spatially controlled deposition of multiple biomolecules onto both planar and
      topographically complex support structures with micrometer resolution. This
      approach is based upon the well-understood photochemical UV crosslinking of
      benzophenone (BP) to solution-phase biomolecules. This is a molecularly general
      strategy that can be utilized to immobilize biomolecules onto any surface
      prefunctionalized with BP. Examples described herein include modification of
      planar and corrugated glass substrates as well as collagen-glycosaminoglycan
      biomaterials configured either as highly porous scaffolds or nonporous membranes
      with a variety of biomolecular targets, including proteins, glycoproteins, and
      carbohydrates. 

PMID- 24560515
TI  - EGFR, KRAS, BRAF-mutations and microsatellite instability are absent in goblet
      cell carcinoids of the appendix.
AB  - Goblet cell carcinoid (GCC) is a rare type of mixed endocrine-exocrine tumor of
      the appendix often showing a clinically aggressive behavior. On a molecular
      basis, this tumor is only poorly understood. To analyze possible molecular
      similarities between GCC and colorectal cancer, we examined 14 cases of GCC for
      mutations in exons 18, 19 and 21 of the EGFR-gene, exon 2 in the KRAS gene and
      for V600E mutations of the BRAF gene. Although the sensitive pyrosequencing
      method was used, no EGFR, KRAS or BRAF mutations could be found. Furthermore,
      using immunohistochemistry, no evidence for microsatellite instabillity (MSI)
      could be found. Despite the partial intestinal differentiation of GCC, our study
      indicates that the molecular pathogenesis of GCC significantly differs from
      conventional colorectal adenocarcinoma. This finding might also have implications
      in adjuvant chemotherapeutic treatment of advanced GCC. 

PMID- 24560516
TI  - Discussion.

PMID- 24560517
TI  - Surgical ablation for atrial fibrillation for two decades: are the results of new
      techniques equivalent to the Cox maze III procedure?
AB  - OBJECTIVES: A significant evolution has occurred in surgical ablation for atrial
      fibrillation (AF) toward alternate energy sources, lesion sets, and approaches,
      with the intent of simplifying the Cox maze III operation and maintaining similar
      outcomes. Because no large comparative studies with long-term follow-up exist, we
      have reviewed our experience. METHODS: From January 1993 to January 2011, 1540
      patients underwent surgical ablation for AF. The operations were performed in
      conjunction with repair of congenital heart disease in 351 (30%) and adult
      acquired disease in 1189 patients (70%). In the 1189 patients, preoperative AF
      was paroxysmal in 598 (50%) and persistent in 591 (50%). The energy sources
      included cut and sew in 521 (44%), cryothermy in 267 (22%), radiofrequency in 262
      (22%), and a combination in 139 patients (12%). The lesion sets included biatrial
      in 810 (68%), isolated pulmonary vein isolation in 269 (23%), and isolated left
      atrial in 110 (9%). AF ablation was performed during isolated mitral valve
      surgery in 516 patients (43%). RESULTS: The median follow-up was 33 months
      (maximum, 20.3 years), and late rhythm follow-up was available for 80%. The cut
      and sew Cox maze III procedure was superior at each follow-up interval (P = .01,
      P = .03, and P < .001). On multivariate analysis, the cut and sew maze procedure
      was independently associated with less risk of recurrent AF at a follow-up period
      of 1 to 5 years (hazard ratio, 0.4; 95% confidence interval, 0.24-0.69; P < .001)
      and >5 years (hazard ratio, 0.23; 95% confidence interval, 0.12-0.42; P < .001)
      for all patients. When performed during isolated mitral valve surgery, the cut
      and sew Cox maze III was also independently associated with less risk of
      recurrent AF at >5 years (hazard ratio, 0.23; 95% confidence interval, 0.08-0.66;
      P = .007). CONCLUSIONS: The cut and sew Cox maze III procedure appears to offer
      significantly greater freedom from AF without antiarrhythmic medications compared
      with alternate energy sources and lesion sets. Although alternate energy sources
      offer the advantage of quicker application and the possibility of minimally
      invasive applications, the Cox maze III operation arguably remains the reference
      standard for the surgical treatment of AF and should still be considered,
      especially for patients for whom AF ablation is of critical importance.

PMID- 24560518
TI  - A common 16p11.2 inversion underlies the joint susceptibility to asthma and
      obesity.
AB  - The prevalence of asthma and obesity is increasing worldwide, and obesity is a
      well-documented risk factor for asthma. The mechanisms underlying this
      association and parallel time trends remain largely unknown but genetic factors
      may be involved. Here, we report on a common ~0.45 Mb genomic inversion at
      16p11.2 that can be accurately genotyped via SNP array data. We show that the
      inversion allele protects against the joint occurrence of asthma and obesity in
      five large independent studies (combined sample size of 317 cases and 543
      controls drawn from a total of 5,809 samples; combined OR = 0.48, p = 5.5 * 10(
      6)). Allele frequencies show remarkable worldwide population stratification,
      ranging from 10% in East Africa to 49% in Northern Europe, consistent with
      discordant and extreme genetic drifts or adaptive selections after human
      migration out of Africa. Inversion alleles strongly correlate with expression
      levels of neighboring genes, especially TUFM (p = 3.0 * 10(-40)) that encodes a
      mitochondrial protein regulator of energy balance and inhibitor of type 1
      interferon, and other candidates for asthma (IL27) and obesity (APOB48R and
      SH2B1). Therefore, by affecting gene expression, the ~0.45 Mb 16p11.2 inversion
      provides a genetic basis for the joint susceptibility to asthma and obesity, with
      a population attributable risk of 39.7%. Differential mitochondrial function and
      basal energy balance of inversion alleles might also underlie the potential
      selection signature that led to their uneven distribution in world populations.

PMID- 24560519
TI  - Exome-based mapping and variant prioritization for inherited Mendelian disorders.
AB  - Exome sequencing in families affected by rare genetic disorders has the potential
      to rapidly identify new disease genes (genes in which mutations cause disease),
      but the identification of a single causal mutation among thousands of variants
      remains a significant challenge. We developed a scoring algorithm to prioritize
      potential causal variants within a family according to segregation with the
      phenotype, population frequency, predicted effect, and gene expression in the
      tissue(s) of interest. To narrow the search space in families with multiple
      affected individuals, we also developed two complementary approaches to exome
      based mapping of autosomal-dominant disorders. One approach identifies segments
      of maximum identity by descent among affected individuals; the other nominates
      regions on the basis of shared rare variants and the absence of homozygous
      differences between affected individuals. We showcase our methods by using exome
      sequence data from families affected by autosomal-dominant retinitis pigmentosa
      (adRP), a rare disorder characterized by night blindness and progressive vision
      loss. We performed exome capture and sequencing on 91 samples representing 24
      families affected by probable adRP but lacking common disease-causing mutations.
      Eight of 24 families (33%) were revealed to harbor high-scoring, most likely
      pathogenic (by clinical assessment) mutations affecting known RP genes. Analysis
      of the remaining 17 families identified candidate variants in a number of
      interesting genes, some of which have withstood further segregation testing in
      extended pedigrees. To empower the search for Mendelian-disease genes in family
      based sequencing studies, we implemented them in a cross-platform-compatible
      software package, MendelScan, which is freely available to the research
      community.

PMID- 24560521
TI  - Aneurysms of the sinus of Valsalva revealed by an acute coronary syndrome.

PMID- 24560522
TI  - Synovial chondromatosis of the temporomandibular joint: CT and MRI findings.

PMID- 24560523
TI  - Hypertrophic cardiomyopathy mimicking STEMI: The role of cardiac magnetic
      resonance imaging in the detection of microvascular coronary dysfunction.

PMID- 24560524
TI  - Effect of silica fouling on the removal of pharmaceuticals and personal care
      products by nanofiltration and reverse osmosis membranes.
AB  - In this study, one reverse osmosis (XLE) and two nanofiltration (NF90 and NF270)
      membranes were fouled by silica to evaluate its effect on the flux decline as
      well as the removal of six pharmaceuticals and personal care products (PPCPs)
      including carbamazapine (CBZ), triclosan (TRI), ibuprofen (IBU), sulfadiazine
      (DIA), sulfamethoxazole (SMX) and sulfamethazine (SMZ) from pH 3 to 10. The
      membranes were characterized by physicochemical properties including
      hydrophobicity, surface morphology and PPCPs adsorption with or without the
      presence of silica fouling to validate the rejection mechanisms of PPCPs. The
      fouling mechanisms were investigated using the modified Hermia model. It was
      found that all membranes with silica fouling showed more severe permeate flux
      decline at low pHs (3 and 5) than at high pHs (8 and 10) by the decomposition of
      nonionized silica particles to form a dense gel layer on membrane surfaces, which
      was hard to be removed by backwash. Silica fouling rendered the membrane surface
      considerably more hydrophilic, and only IBU, TRI and SMZ were adsorbed on
      membranes. Silica fouling on tight membranes (NF90 and XLE) can promote rejection
      of most PPCPs because the dense fouling layer could supply membrane with
      synergistic steric hindrance to reduce the transportation of PPCPs across
      membrane surface, implying that size exclusion is the dominating mechanism. While
      for loose NF270, electrostatic repulsion dominates by enhanced rejection of PPCPs
      as pH increased. Although fouling layer could provide extra steric hindrance for
      NF270, its effect was overwhelmed by the accompanied cake-enhanced concentration
      polarization phenomenon (CEOP). CEOP impeded back diffusion of PPCPs into the
      feed solution, trapped and accumulated PPCPs on membrane surface so as to
      increase their diffusion across membrane. At all pH levels, intermediate blocking
      and gel layer formation was the major fouling mechanism for tight and loose
      membrane, respectively. 

PMID- 24560526
TI  - [Measurement of changes in end expiratory lung volume by electric impedance
      tomography during general anesthesia].

PMID- 24560525
TI  - Revealing the role of the autonomic nervous system in the development and
      maintenance of Goldblatt hypertension in rats.
AB  - Despite extensive use of the renovascular/Goldblatt model of hypertension-2K-1C,
      and the use of renal denervation to treat drug resistant hypertensive patients,
      autonomic mechanisms that underpin the maintenance of this hypertension are
      important yet remain unclear. Our aim was to analyse cardiovascular autonomic
      function by power spectral density analysis of both arterial pressure and pulse
      interval measured continuously by radio telemetry for 6weeks after renal artery
      clipping. Mean arterial pressure increased from 106+/-5 to 185+/-2mmHg during
      5weeks post clipping when it stabilized. A tachycardia developed during the 4th
      week, which plateaued between weeks 5 and 6. The gain of the cardiac vagal
      baroreflex decreased immediately after clipping and continued to do so until the
      5th week when it plateaued (from -2.4+/-0.09 to -0.8+/-0.04bpm/mmHg; P<0.05). A
      similar time course of changes in the high frequency power spectral density of
      the pulse interval was observed (decrease from 13.4+/-0.6 to 8.3+/-0.01ms(2);
      P<0.05). There was an increase in both the very low frequency and low frequency
      components of systolic blood pressure that occurred 3 and 4weeks after clipping,
      respectively. Thus, we show for the first time the temporal profile of autonomic
      mechanisms underpinning the initiation, development and maintenance of
      renovascular hypertension including: an immediate depression of cardiac
      baroreflex gain followed by a delayed cardiac sympathetic predominance; elevated
      sympathetic vasomotor drive occurring after the initiation of the hypertension
      but coinciding during its mid-development and maintenance.

PMID- 24560527
TI  - [Ultrasound guided paravertebral block is an efficient technique for
      postoperative pain management in paediatric ambulatory surgery].

PMID- 24560528
TI  - [A stroke during pregnancy revealing an abdominal aorta coarctation].

PMID- 24560530
TI  - Environments of care.

PMID- 24560529
TI  - A three-year follow-up of congenital adrenal hyperplasia newborn screening.
AB  - OBJECTIVE: congenital adrenal hyperplasia (CAH) newborn screening can prevent
      neonatal mortality in children with the salt-wasting form of the disease and
      prevent incorrect gender assignments, which can occur in females. However, the
      occurrence of false-positive results in preterm or low-birth-weight newborns
      creates some diagnostic difficulties, with consequent therapeutic implications.
      This study aimed to report the results of a pilot project for neonatal CAH
      screening conducted in the state of Minas Gerais, Brazil from 09/2007 to 05/2008
      with a three-year follow-up. METHODS: dried blood specimens were collected on
      filter paper cards three to seven days after birth of all newborns in the period.
      Samples were analyzed for 17-hydroxyprogesterone using an enzyme-linked
      immunosorbent assay (ELISA). RESULTS: a total of 159,415 children were screened.
      The apparent incidence of the classic variant of the disease was 1:9,963, based
      on initial diagnoses following newborn screening. During the follow-up period,
      eight of 16 children initially diagnosed with CAH were reclassified as
      unaffected, resulting in a revised incidence of 1:19,927. The false-positive rate
      was 0.31%, and the positive predictive value was 2.1%. Sensitivity and
      specificity were 100% and 99.7%, respectively. CONCLUSIONS: newborn screening is
      an important public health policy in developing countries such as Brazil, where
      CAH remains underdiagnosed. It has great potential to identify children with the
      disease who otherwise cannot be diagnosed earlier. Long-term follow-up and
      monitoring of all children with positive screening results are crucial to ensure
      a correct diagnosis and to calculate a reliable incidence ratio of the disease.

PMID- 24560520
TI  - Gene-centric meta-analysis in 87,736 individuals of European ancestry identifies
      multiple blood-pressure-related loci.
AB  - Blood pressure (BP) is a heritable risk factor for cardiovascular disease. To
      investigate genetic associations with systolic BP (SBP), diastolic BP (DBP), mean
      arterial pressure (MAP), and pulse pressure (PP), we genotyped ~50,000 SNPs in up
      to 87,736 individuals of European ancestry and combined these in a meta-analysis.
      We replicated findings in an independent set of 68,368 individuals of European
      ancestry. Our analyses identified 11 previously undescribed associations in
      independent loci containing 31 genes including PDE1A, HLA-DQB1, CDK6, PRKAG2,
      VCL, H19, NUCB2, RELA, HOXC@ complex, FBN1, and NFAT5 at the Bonferroni-corrected
      array-wide significance threshold (p < 6 * 10(-7)) and confirmed 27 previously
      reported associations. Bioinformatic analysis of the 11 loci provided support for
      a putative role in hypertension of several genes, such as CDK6 and NUCB2.
      Analysis of potential pharmacological targets in databases of small molecules
      showed that ten of the genes are predicted to be a target for small molecules. In
      summary, we identified previously unknown loci associated with BP. Our findings
      extend our understanding of genes involved in BP regulation, which may provide
      new targets for therapeutic intervention or drug response stratification.

PMID- 24560531
TI  - Management of focal epilepsy in adults treated with polytherapy in France: the
      direct cost of drug resistance (ESPERA study).
AB  - PURPOSE: To estimate the direct costs associated with the current management of
      focal epilepsy in adults treated with a combination of antiepileptic drugs (AEDs)
      in France and the supplementary costs of drug resistant epilepsy as defined by
      the International League Against Epilepsy (ILAE) in 2009. METHODS: ESPERA was a
      multicentre, observational, cross-sectional study conducted in France in 2010. A
      random sample of neurologists, including specialists in epilepsy, prospectively
      enrolled adults with focal epilepsy treated with a combination of AEDs.
      Investigators classified their patients according to the 2009 ILAE criteria for
      drug resistance and this classification was then reviewed by two experts. All
      items of healthcare resource use associated with epilepsy over the previous year
      were documented retrospectively and valued from a societal perspective. RESULTS:
      Seventy-one neurologists enrolled 405 patients. After experts' review, 70.6% of
      patients were classified with drug-resistant epilepsy, 22.4% with drug-responsive
      epilepsy and 7% with undefined epilepsy. The mean annual epilepsy-related direct
      costs per patient were ?4485+/-?4313 in patients with drug-resistant epilepsy
      compared to ?1926+/-?1795 in patients with drug-responsive epilepsy. In these two
      groups, costs of AEDs were estimated at ?2603 and ?1544, respectively. Patients
      with drug-resistant epilepsy were more often hospitalised (mean annual cost:
      ?1270 vs. ?97) and underwent more additional tests (mean annual cost: ?194 vs.
      ?53). CONCLUSION: The direct cost of focal epilepsy in adults on AED combinations
      was estimated at ?3850/patient/year. Drug resistance, as defined by the 2009 ILAE
      criteria, resulted in significant extra costs which varied with seizure
      frequency.

PMID- 24560532
TI  - [Exposure pathways to pesticides in schoolchildren in the Province of Talca,
      Chile].
AB  - OBJECTIVE: To describe pesticide concentrations in distinct environmental
      matrices at two time points (low and high seasons in local agricultural
      production) and to estimate the association between the presence of pesticide
      residues in matrices and the use of pesticides in the home with the
      sociodemographic variables of schoolchildren in the Province of Talca, Chile.
      METHODS: A cross-sectional study was conducted in 190 schoolchildren. Families
      were surveyed about their children's vegetable consumption in school and at home,
      the use of pesticides in the home, and other sociodemographic variables.
      Additionally, we measured pesticide residues in vegetables and water consumed by
      the schoolchildren and in the soil of 14 schools. RESULTS: At both time points,
      the vegetable matrix had the highest pesticide concentration, both in urban and
      rural schoolchildren. The most common pesticide residues in vegetables were
      chlorpyrifos, diphenylamine, pyrimethanil, and thiabendazole. In the home,
      pyrethroid and organophosphate pesticides were mainly used in summer. Dangerous
      pesticide residues such as azinphos methyl and dimethoate were found in
      vegetables consumed by the children in schools and households, and
      organochlorines were found in the soil in some schools. CONCLUSIONS: Pesticide
      exposure should be limited and the health effects related to pesticide exposure
      should be assessed in the school population.

PMID- 24560533
TI  - Physical activity environment measurement and same source bias.

PMID- 24560534
TI  - Frequency of occurrence and characteristics of primary pancreatic lymphoma during
      endoscopic ultrasound guided fine needle aspiration: a retrospective study.
AB  - BACKGROUND: Primary pancreatic lymphoma is a rare tumour of the pancreas. Data on
      the role of endoscopic ultrasound guided fine needle aspiration for its diagnosis
      are scant. AIM: To identify the frequency of occurrence, sonographic
      characteristics and cytological findings that are predictive of primary
      pancreatic lymphoma. METHODS: Pancreatic lymphoma cases were identified by
      retrospective review of solid pancreatic masses over 10-year period. RESULTS:
      12/2397 (0.5%) lesions were identified. Patients were predominantly white (92%)
      and male (58%). Mean largest dimension was 47.5mm and 83.3% were located in the
      head. The mass appeared heterogeneous in 75% and peripancreatic lymphadenopathy
      was noted in 58%. None of the patients showed features of chronic pancreatitis or
      pancreatic ductal dilation. Rapid onsite analysis revealed atypical lymphocytes
      in 92%. Flow cytometry confirmed diagnosis in 75% of cases. CONCLUSIONS: Primary
      pancreatic lymphoma is encountered in 0.5% of patients undergoing endoscopic
      ultrasound guided fine needle aspiration. A large heterogeneous mass, in the
      absence of chronic pancreatitis or pancreatic duct dilation that reveals atypical
      lymphocytes on fine needle aspiration is suggestive.

PMID- 24560536
TI  - Autophagy in arsenic carcinogenesis.
AB  - Chronic exposure to arsenic may cause cancer. Many mechanisms have been suggested
      for arsenic carcinogenesis. Autophagy, an evolutionarily conserved cellular
      catabolic mechanism, has been implicated in cancer biology. Although being
      claimed as a type of cell death, autophagy may actually serve as a cell self
      defense mechanism. In this review article, current understandings of the
      mechanisms of arsenic carcinogenesis, functions of autophagy and the role of
      autophagy in arsenic carcinogenesis are discussed. 

PMID- 24560535
TI  - Development and validation of a computer-based learning module for wrist
      arthroscopy.
AB  - The objective of this study was to develop and validate a computer-based module
      for wrist arthroscopy to which a group of experts could consent. The need for
      such a module was assessed with members of the European Wrist Arthroscopy Society
      (EWAS). The computer-based module was developed through several rounds of
      consulting experts on the content. The module's learning enhancement was tested
      in a randomized controlled trial with 28 medical students who were assigned to
      the computer-based module group or lecture group. The design process led to a
      useful tool, which is supported by a panel of experts. Although the computer
      based module did not enhance learning, the participants did find the module more
      pleasant to use. Developing learning tools such as this computer-based module can
      improve the teaching of wrist arthroscopy skills. 

PMID- 24560538
TI  - Preparation and evaluation of novel pyrazolo[1,5-a]pyrimidine acetamides, closely
      related to DPA-714, as potent ligands for imaging the TSPO 18kDa with PET.
AB  - A series of four novel analogues of DPA-714, bearing a fluoroalkynyl side chain
      (with a length ranging from three to six carbon atoms) in replacement of the
      fluoroethoxy motif, have been synthetized in six steps from commercially
      available methyl 4-iodobenzoate. The synthetic strategy for the preparation of
      these N,N-diethyl-2-(2-(4-(omega-fluoroalk-1-ynyl)phenyl)-5,7
      dimethylpyrazolo[1,5-a]pyrimidin-3-yl)acetamides (7a-d) consisted in derivatizing
      a key iodinated building block featuring the pyrazolopyrimidine acetamide
      backbone of DPA-714, by Sonogashira couplings with various alkynyl reagents. The
      resulting alkynols were subsequently fluorinated, yielding the expected target
      derivatives. All four analogues exhibited slightly higher affinity and
      selectivity towards the TSPO 18kDa (Ki vs [(3)H]PK11195: 0.35-0.79nM; Ki vs
      [(3)H]flunitrazepam: >1000nM) when compared to DPA-714 (Ki vs [(3)H]PK11195:
      0.91nM; Ki vs [(3)H]flunitrazepam: >1000nM). Lipophilicities (HPLC, logD7.4)
      increased with the chain length (from 3.6 to 4.3) and were significantly higher
      than the one determined for DPA-714 (2.9). Preliminary in vitro metabolism
      evaluation using rat microsomal incubations and LC-MS analyses showed, for all
      four novel analogues, the absence of defluorinated metabolites. Among them, the
      fluoropentynyl compound, DPA-C5yne (7c), was selected, labelled in one single
      step with fluorine-18 from the corresponding tosylate and in vivo evaluated with
      PET on our in-house-developed rat model of acute local neuroinflammation. 

PMID- 24560539
TI  - Discovery of 1,3,4-oxidiazole scaffold compounds as inhibitors of superoxide
      dismutase expression.
AB  - The treatment of neurodegenerative diseases is difficult because of multiple
      etiologies and the interplay of genetics and environment as precipitating
      factors. In the case of amyotrophic lateral sclerosis (ALS), we have knowledge of
      a handful of genes that cause disease when mutated. However, drugs to counteract
      the effect of genetic mutations have not yet been found. One of the causative
      genes, Cu, Zn-superoxide dismutase (SOD1) is responsible for about 10-15% of the
      genetically linked autosomal dominant disease. Our rationale was that compounds
      that reduce expression of the mutant protein would be beneficial to slow onset
      and/or disease progression. We screened candidate compounds using a cell-based in
      vitro assay for those that reduce mutant SOD1 (G93A) protein expression. This led
      to the discovery of 2-[3-iodophenyl)methylsulfanyl]-5pyridin-4-yl-1,3,4
      oxadiazole, a known protein kinase inhibitor that decreases G93A-SOD1 expression
      in vitro and in the brain and spinal cord in vivo. However, this compound has a
      biphasic dose response curve and a likely toxophore which limit its therapeutic
      window for chronic disease such as ALS. Therefore, we designed and tested a
      focused library of analogs for their ability to decrease SOD1 expression in
      vitro. This exercise resulted in the identification of a lead compound with
      improved drug-like characteristics and activity. Development of small molecules
      that reduce the expression of etiologically relevant toxic proteins is a strategy
      that may also be extended to familial ALS linked to gain of function mutations in
      other genes. 

PMID- 24560540
TI  - Preparation and optimization of new 4-(2-(indolin-1-yl)-2-oxoethyl)-2
      morpholinothiazole-5-carboxylic acid and amide derivatives as potent and
      selective PI3Kbeta inhibitors.
AB  - In our continuous efforts to identify and develop novel targeted cancer
      treatments, a new morpholino-thiazole scaffold active against PI3Kbeta has been
      identified. This Letter reports the optimization of this compound class to
      develop PI3Kbeta isoform-selective inhibitors with suitable pharmacological
      properties. 

PMID- 24560542
TI  - Phambili: moving forward without the blindfold.

PMID- 24560543
TI  - Increased requirement for minute ventilation and negative arterial to end-tidal
      carbon dioxide gradient may indicate malignant hyperthermia.
AB  - Characteristic signs of malignant hyperthermia (MH) include unexplained
      tachycardia, increased end-tidal carbon dioxide (Etco2) concentration, metabolic
      and respiratory acidosis, and an increase in body temperature above 38.8 degrees
      C. We present the case of a patient with highly probable MH. In addition to sinus
      tachycardia and metabolic and respiratory acidosis, this patient also had a
      negative arterial to Etco2 gradient and an increased requirement for minute
      ventilation to maintain a normal Etco2 concentration, with signs of increased CO2
      production. Despite these signs of MH, the patient's rectal temperature
      monitoring equipment did not show an increase in temperature, although the
      temperature measured in the mouth was increased. This case illustrates the
      unreliability of measuring rectal temperature as a means of reflecting body
      temperature during MH and the usefulness of increased CO2 production signs in
      helping to diagnose MH.

PMID- 24560544
TI  - Insights from insects about adaptive social information use.
AB  - Copying others can greatly improve individual fitness and is fundamental for the
      organisation of societies. Yet in some situations it is better to ignore social
      information and either explore the world individually or use personal information
      obtained through prior experience. Insects provide excellent models to study the
      strategic use of social information, but insights from recent research have
      rarely been viewed in the light of social learning strategies. Here we discuss
      how insects tailor their reliance on social information to those circumstances
      for which it is most beneficial, and suggest that insects and vertebrates use
      similar information-use strategies. We highlight future research avenues,
      including the use of molecular tools to study the genetic and genomic basis of
      social information use. 

PMID- 24560541
TI  - Recombinant adenovirus type 5 HIV gag/pol/nef vaccine in South Africa: unblinded,
      long-term follow-up of the phase 2b HVTN 503/Phambili study.
AB  - BACKGROUND: The HVTN 503/Phambili study, which assessed the efficacy of the Merck
      Ad5 gag/pol/nef subtype B HIV-1 preventive vaccine in South Africa, was stopped
      when futility criteria in the Step study (assessing the same vaccine in the
      Americas, Caribbean, and Australia) were met. Here we report long-term follow-up
      data. METHODS: HVTN 503/Phambili was a double-blind, placebo-controlled,
      randomised trial that recruited HIV-1 uninfected, sexually active adults aged 18
      35 years from five sites in South Africa. Eligible participants were randomly
      assigned (1:1) by computer-generated random numbers to either vaccine or placebo,
      stratified by site and sex. Cox proportional hazards models were used to estimate
      HIV-1 infection in the modified intention-to-treat cohort, all of whom were
      unmasked early in follow-up. The trial is registered with ClinicalTrials.gov,
      number NCT00413725 and the South African National Health Research Database,
      number DOH-27-0207-1539. FINDINGS: Between Jan 24, 2007, and Sept 19, 2007, 801
      participants (26.7%) of a planned 3000 were randomly assigned (400 to vaccine,
      401 to placebo); 216 (27%) received only one injection, 529 (66%) received only
      two injections, and 56 (7%) received three injections. At a median follow-up of
      42 months (IQR 31-42), 63 vaccine recipients (16%) had HIV-1 infection compared
      with 37 placebo recipients (9%; adjusted HR 1.70, 95% CI 1.13-2.55; p=0.01). Risk
      for HIV-1 infection did not differ according to the number of vaccinations
      received, sex, circumcision, or adenovirus type 5 (Ad5) serostatus. Differences
      in risk behaviour at baseline or during the study, or annualised dropout rate
      (7.7% [95% CI 6.2-9.5] for vaccine recipients vs 8.8% [7.1-10.7] for placebo
      recipients; p=0.40) are unlikely explanations for the increased rate of HIV-1
      infections seen in vaccine recipients. INTERPRETATION: The increased risk of HIV
      1 acquisition in vaccine recipients, irrespective of number of doses received,
      warrants further investigation to understand the biological mechanism. We caution
      against further use of the Ad5 vector for HIV vaccines. FUNDING: National
      Institute of Allergy and Infectious Diseases, Merck, and South African Medical
      Research Council.

PMID- 24560545
TI  - Thrombus composition in acute ischemic stroke: a histopathological study of
      thrombus extracted by endovascular retrieval.
AB  - BACKGROUND AND PURPOSE: The composition of occlusive thrombus in acute ischemic
      stroke may affect treatment success. Neuroimaging characteristics may correlate
      with thrombus composition. In this study we aimed to investigate the relationship
      between the hyperdense artery sign (HAS) on imaging and thrombus composition.
      MATERIALS AND METHODS: Acute ischemic stroke patients who underwent endovascular
      thrombus retrieval from 2010-2012 were prospectively recruited. One blinded
      pathologist prepared the histology sections of retrieved thrombi whereby staining
      with haematoxylin and eosin and CD34 immunostain were performed. Histology
      sections were categorised into 4 phases of thrombus formation: red blood cell
      (RBC) dominant, RBC proportion equal to fibrin, fibrin dominant and organised
      fibrin. Computed tomography (CT) brain scans were assessed for HAS. Fisher's
      exact test was performed to identify an association between HAS and thrombus
      composition. RESULTS: Forty patients were included. The mean age was 65.6+/-12.9
      years and 67.5% were male. Atrial fibrillation was detected in 19 (47.5%)
      patients, diabetes mellitus in 6 (15.0%), hypercholesterolaemia in 11 (27.5%),
      hypertension in 20 (50.0%) and previous stroke or transient ischemic attack in 8
      (20.0%) patients. Of the retrieved thrombi, 11 (27.5%) were RBC dominant, 11
      (27.5%) RBC proportion was equal to fibrin, 7 (17.5%) fibrin dominant and 11
      (27.5%) organised fibrin pathology. HAS was present in 29 (72.5%) patients and
      was significantly associated with thrombus early phase pathology (P<0.05).
      CONCLUSION: HAS was significantly associated with early phase thrombus
      composition. This may enable the prediction of thrombus composition and allow for
      targeted selection of therapeutic modality.

PMID- 24560546
TI  - Narrowing the normal range for lateral ankle ligament stability with stress
      radiography.
AB  - Stress radiographs are commonly performed to evaluate lateral ankle ligament
      stability; however, little agreement exists on the physiologic limits obtained
      from the anterior drawer and talar tilt stress tests. Published studies have
      reported the normal range for the anterior drawer test to be 3 to 10 mm and the
      normal range for the talar tilt test to be 0 degrees  to 23 degrees  for the
      uninjured ankle, leading to inconsistent interpretation. The primary objective of
      the present study was to narrow the threshold for the diagnosis of ankle ligament
      injury using stress radiographs by refining the values seen in the normal ankle.
      An improved understanding of normal ankle motion could allow for a more accurate
      determination of ligament injury using stress imaging. Conducted in a simplified,
      yet reproducible, manner, we hoped the present study would draw a parallel with
      generalized use in an office setting and would allow physicians the ability to
      more effectively diagnose ankle ligament injury. Bilateral radiographic images of
      anterior drawer and talar tilt stress tests were taken of 50 participants (100
      ankles) with no history of ankle fracture or surgical intervention for ankle
      instability. Participants with a previous ankle sprain were later excluded from
      the result computations. Factors such as patient age and gender were evaluated.
      In the final analysis, 46 participants (76 ankles) were included, with a mean
      anterior drawer test result of 2.00 mm +/- 1.71 mm and talar tilt test result of
      3.39 degrees  +/- 2.70 degrees  in the normal ankle. The results of the present
      study suggest that stress radiographs for lateral ankle stability can be
      performed in a simple and reliable manner. These results also support a much
      lower threshold for the diagnosis of lateral ankle injury than previously
      reported. 

PMID- 24560547
TI  - Infrared technology for estrus detection and as a predictor of time of ovulation
      in dairy cows in a pasture-based system.
AB  - The development and application of an algorithm to assess the ability of an
      infrared thermography (IRT) device to predict cows in estrus and about to ovulate
      was investigated. Twenty cows were synchronized using a controlled internal drug
      release and PGF2alpha. Vulval and muzzle temperatures were measured every 12
      hours from controlled internal drug release insertion to 32 hours after PGF2alpha
      treatment and then every 4 hours until ovulation occurred or until 128 hours
      after PGF2alpha treatment (whichever occurred first). Thermal images obtained
      with a FLIR T620 series infrared camera were analyzed using ThermaCAM Researcher
      Professional 2.9 software. Cows were also monitored for behavioral signs of
      estrus and color changes of an Estrotect applied to the tail head of each cow 36
      hours after PGF2alpha treatment. Algorithms were developed by adjusting body
      surface temperature of individual animals for ambient temperature and humidity
      during each observation period, and were expressed as a deviation from the
      baseline temperature. Of the 20 cows enrolled in this study, 12 (60%) ovulated.
      An IRT estrus alert was defined using different thresholds (D = 1  degrees C,
      1.25  degrees C, and 1.5  degrees C). Sensitivity and specificity to predict
      estrus depended upon the chosen threshold level. At a threshold D = 1  degrees C,
      the highest sensitivity (92%; n = 11) and the lowest specificity (29%) and
      positive predictive value (64%) were observed. Conversely, D = 1.5  degrees C
      resulted in sensitivity of 75%, specificity of 57%, and positive predictive value
      of 69%. The mean +/- standard deviation intervals between onset and the end of
      IRT estrus alert to ovulation were 30.7 +/- 8.2 and 13.3 +/- 7.7 hours,
      respectively. Ovulation occurred 24 to 47 hours after the onset of the IRT estrus
      alert for eight out of the 11 ovulated cows (73%). Although the sensitivity of
      the IRT alert was greater than visual observation (67%) and Estrotect activation
      (67%), the specificity and positive predictive value were lower than these two
      aids (i.e., the IRT overpredicted the incidence of ovulation). Results presented
      indicate that IRT shows some potential as an estrus detection aid; however,
      further studies investigating the potential to improve the specificity and
      capturing data throughout entire 21-day reproductive cycles would be worthwhile. 

PMID- 24560548
TI  - Morphometric analysis of fetal development of Cavia porcellus (Linnaeus, 1758) by
      ultrasonography--pilot study.
AB  - Measurements on the growth process and placental development of the embryo and
      fetuses of Cavia porcellus were carried out using ultrasonography. Embryo, fetus,
      and placenta were monitored from Day 15 after mating day to the end of gestation.
      Based on linear and quadratic regressions, the following morphometric analysis
      showed a good indicator of the gestational age: placental diameter, biparietal
      diameter, renal length, and crown rump. The embryonic cardiac beat was first
      detected at an average of 22.5 days. The placental diameter showed constant
      increase from beginning of gestation then remained to term and presented a
      quadratic correlation with gestational age (r(2) = 0.89). Mean placental diameter
      at the end of pregnancy was 3.5 +/- 0.23 cm. By Day 30, it was possible to
      measure biparietal diameter, which followed a linear pattern of increase up to
      the end of gestation (r(2) = 0.95). Mean biparietal diameter in the end of
      pregnancy was 1.94 +/- 0.03 cm. Kidneys were firstly observed on Day 35 as
      hyperechoic structures without the distinction of medullar and cortical layers,
      thus the regression model equation between kidney length and gestational age
      presents a quadratic relationship (r(2) = 0.7). The crown rump presented a simple
      linear growth, starting from 15 days of gestation, displaying a high correlation
      with the gestational age (r(2) = 0.9). The offspring were born after an average
      gestation of 61.3 days. In this study, we conclude that biparietal diameter,
      placental diameter, and crown rump are adequate predictive parameters of
      gestational age in guinea pigs because they present high correlation index. 

PMID- 24560549
TI  - Comparative proteomic analysis of hearts of adult SCNT Bama miniature pigs (Sus
      scrofa).
AB  - This study aims to determine the effects of SCNT on cardiac development of SCNT
      pigs through proteomic methods. Heart proteins from three adult SCNTs and two
      normal reproductive Bama miniature pigs were extracted, separated, and identified
      via comparative proteomic methods, including two-dimensional gel electrophoresis,
      mass spectrometry, and Western blot. Eleven differentially expressed spots were
      identified as differentially expressed proteins, of which five spots were
      upregulated proteins such as cardiac myosin heavy chain, cathepsin D, and heat
      shock protein beta-1 (HSP27). By contrast, six spots were downregulated proteins
      such as alpha skeletal muscle and actin. The results also demonstrated that
      nuclear transfer might result in abnormal expression of some important proteins
      in hearts from SCNT pigs, and affect the cardiac development in SCNT pigs'
      survival. 

PMID- 24560550
TI  - Was the Clean Water Act effective?

PMID- 24560551
TI  - Observed changes in radiographic measurements of the first ray after frontal
      plane rotation of the first metatarsal in a cadaveric foot model.
AB  - We observed the changes in the angular measurements commonly used in the
      evaluation of the first metatarsal and first metatarsophalangeal joint in
      cadaveric specimens before and after frontal plane rotation of the first
      metatarsal. Measurements of the first and second intermetatarsal angle (IMA),
      hallux abductus angle, proximal articular set angle, and tibial sesamoid position
      (TSP) were taken after varying degrees of varus and valgus rotation of the first
      metatarsal. Standard dorsoplantar radiographs were taken at 0 degrees , 10
      degrees , 20 degrees , and 30 degrees  of valgus rotation of the first metatarsal
      and repeated at 10 degrees , 20 degrees , and 30 degrees  varus rotation of the
      first metatarsal. The data were analyzed using a mixed linear model to compare
      the change in each angle measurement over the range of valgus and varus rotation.
      The change in the TSP was significant in both valgus and varus rotations (p =
      .0004 and p = .028, respectively), an increase in valgus rotation causing an
      increase in the TSP and an increase in varus rotation causing a decrease in TSP.
      The change in the IMA was significant compared with valgus rotation (p = .028),
      showing that as the valgus rotation increased, the IMA also increased. However,
      compared with the varus rotation, the correlation was not significant (p = .18).
      The proximal articular set angle and hallux abductus angle measurements, compared
      with metatarsal rotation, showed positive trends but were not statistically
      significant. From our results and a review of the published data, we have
      hypothesized that frontal plane rotation of the first metatarsal is an integral
      component of hallux abducto valgus pathologic features, specifically in relation
      to the TSP and IMA. 

PMID- 24560552
TI  - Outcomes of scleral-sutured conventional and aniridia intraocular lens
      implantation performed in a university hospital setting.
AB  - PURPOSE: To evaluate the outcomes of transscleral sutured posterior chamber
      intraocular lens (PC IOL) implantation. SETTING: Public university hospital,
      Auckland, New Zealand. DESIGN: Retrospective case series. METHODS: A modified no
      touch transscleral sutured PC IOL implantation technique with a 1-piece monofocal
      IOL (Alcon CZ70BD) or an aniridia IOL (type 67G, Morcher) was assessed. RESULTS:
      Seventy-eight cases (80.8% men; 53.9% aphakic) were identified. The mean follow
      up was 35.5 months and the mean age at surgery, 41 years+/-21 (SD). The
      preoperative corrected distance visual acuity (CDVA) was worse than 6/30 in
      66.7%. Indications included ocular trauma (46.2%), nontraumatic crystalline lens
      subluxation (16.7%), post-complicated cataract surgery (10.3%), idiopathic IOL
      dislocation (10.3%), and congenital cataract/aphakia (10.3%). An aniridia IOL was
      required in 39.7% of eyes. There were no significant intraoperative complications
      in 74.4% of eyes. Postoperative complications included transient corneal edema
      (15.4%), wound leak requiring resuturing (7.7%), retinal detachment (7.7%), and
      cystoid macular edema (6.4%). One eye (1.3%) developed suture breakage-related
      late IOL dislocation. Overall, 91.3% of eyes had improved visual acuity or were
      within 1 line of the presenting CDVA. In eyes with a guarded prognosis, 34.8%
      achieved a CDVA of 6/12 or better and 43.5% a CDVA of 6/15 to 6/48. In the better
      prognosis group, 73.9% achieved a CDVA of better than 6/12 and all achieved
      better than 6/30. CONCLUSIONS: Scleral-sutured IOLs achieved good visual outcomes
      in a public hospital setting. The rate of complications was moderate in this
      series with a high proportion of severe ocular trauma and a large percentage of
      aniridia IOLs. FINANCIAL DISCLOSURE: No author has a financial or proprietary
      interest in any material or method mentioned.

PMID- 24560553
TI  - Intraoperative vertical gas breakthrough during clear corneal incision creation
      with the femtosecond cataract laser.
AB  - We report the occurrence and management of intraoperative vertical gas
      breakthrough during clear corneal incision creation with the femtosecond laser
      (Catalys) in 2 patients. Both eyes were managed by creation of a keratome
      incision, and the surgery was completed uneventfully. There were no postoperative
      complications. We believe that wound architecture and corneal clarity in the area
      of wound creation predispose to the occurrence of vertical gas breakthrough.
      Careful inspection of wound integrity can provide clues to an incomplete wound.
      FINANCIAL DISCLOSURE: Neither author has a financial or proprietary interest in
      any material or method mentioned.

PMID- 24560554
TI  - Effect of femtosecond laser-created clear corneal incision on corneal topography.
AB  - PURPOSE: To evaluate changes in anterior corneal topography after femtosecond
      laser-created clear corneal incisions (CCIs). SETTING: Fondazione G.B. Bietti
      IRCCS, Rome, Italy. DESIGN: Comparative case series. METHODS: Phacoemulsification
      was performed through a 2.75 mm incision. In the study group, a 3-plane CCI was
      created using a 150 kHz femtosecond laser. In the control group, a single-plane
      angled CCI was created using disposable knives. Placido disk corneal topography
      was performed preoperatively and 1 week and 1 month postoperatively. Central
      curvature (simulated keratometry [K]) and local changes in anterior corneal
      topography at the CCI site were evaluated and compared between groups. RESULTS:
      No significant changes in the mean simulated K values were found in either group
      postoperatively (P>.05). The preoperative to 1-month postoperative mean simulated
      K ranged between 43.30 diopters (D)+/-0.82 (SD) and 43.17+/-0.82 D in the study
      group and between 43.34+/-1.44 D and 43.29+/-1.48 D in the control group. The
      method of CCI creation significantly influenced the changes in the anterior
      central topography during the first month postoperatively (P<.001). Greater
      steepening of the incision edges was found in the control group (mean 36.60+/
      4.13 D to 37.74+/-2.39 D) than in the study group (mean 38.81+/-2.91 D to 39.15+/
      4.48 D). CONCLUSIONS: The 2.75 mm 3-plane femtosecond CCIs induced slight changes
      in the anterior central corneal topography, similar to single-plane angled manual
      incisions. Topographic differences between the femtosecond method and manual
      method were found at the CCI site. FINANCIAL DISCLOSURE: No author has a
      financial or proprietary interest in any material or method mentioned.

PMID- 24560555
TI  - [Behcet's disease revealed by an aneurysm of the splenic artery].

PMID- 24560556
TI  - Does a maternal-fetal medicine-centered labor and delivery coverage model put the
      'M' back in MFM?
AB  - OBJECTIVE: Maternal morbidity is increasing in the United States. Our objectives
      were to examine whether a labor and delivery (L&D) provider model with regular
      maternal-fetal medicine (MFM) coverage decreases the rates of maternal morbidity
      during delivery hospitalizations and has an impact on obstetrician-gynecologist
      residents' perceptions of safety and education. STUDY DESIGN: We performed a
      retrospective cohort study to compare the rates of maternal morbidity before and
      after the implementation of an MFM-centered coverage model on L&D. Outcomes were
      identified using International Classification of Diseases, ninth revision, codes.
      The primary outcome was a composite of severe maternal morbidity. Additionally,
      obstetrician-gynecologist residents completed an anonymous survey asking them to
      compare coverage models, and their Council on Resident Education in Obstetrics
      and Gynecology examination scores were compared. RESULTS: Data from 4715
      deliveries were included. There were no differences in composite morbidity or
      individual adverse outcomes. Most residents (81.3%) preferred the new provider
      model, with median 5-point Likert scores indicating perceived increases in safety
      and education. Mean Council on Resident Education in Obstetrics and Gynecology
      scores improved in the 18 residents exposed to both models. CONCLUSION: Although
      the MFM-centered provider model appears to have had a positive impact on
      residents' perceptions of safety and education, it was not associated with
      significant changes in severe maternal morbidity.

PMID- 24560557
TI  - REMOVED: The relationship between primary cesarean delivery skin incision type
      and wound complications in women with morbid obesity.
AB  - This article has been removed: please see Elsevier Policy on Article Withdrawal
      (http://www.elsevier.com/locate/withdrawalpolicy).This article has been removed
      at the request of the Editors-in-Chief and Authors.The original publication
      reported that univariate analysis showed that a vertical skin incision in obese
      women undergoing Cesarean delivery was associated with a higher odds ratio for
      wound complications than a transverse skin incision. Multivariable analyses
      showed a reversal of the association (i.e. the odds of wound complications were
      lower in women with a vertical skin incision). However, there was an error in the
      way the variable was entered in the logistic analysis. Re-analysis with the
      correct coding of the variable indicates that a transverse skin incision is
      associated with decreased odds of wound complication compared to a vertical skin
      incision.

PMID- 24560559
TI  - CD34 and alpha smooth muscle actin distinguish verrucous hyperplasia from
      verrucous carcinoma.
AB  - OBJECTIVE: This study evaluated the use of stromal biomarkers CD34 and alpha
      smooth muscle actin (alpha-SMA) to distinguish verrucous carcinoma (VC) from
      verrucous hyperplasia (VH). STUDY DESIGN: Thirteen VH, 15 VC, 20 squamous cell
      carcinoma (SCC), and 16 of uninvolved adjacent stroma specimens were analyzed for
      alpha-SMA and CD34 expression by immunohistochemistry. RESULTS: Stromal alpha-SMA
      positivity was observed in 100% (20 of 20) of the SCC and in 93% (14 of 15) of
      the VC, whereas none of the VH (0 of 13) or adjacent uninvolved stroma (0 of 16)
      demonstrated alpha-SMA reactivity. Stromal CD34 positivity was observed in 100%
      (13 of 13) of VH and adjacent stroma (16 of 16), while 20% (3 of 15) of VC and
      11% (2 of 18) of SCC stroma expressed CD34. The SCC and VC groups differed
      significantly from the VH and uninvolved stroma groups for both alpha-SMA and
      CD34 expression (P < .0001). CONCLUSIONS: Stromal CD34 and alpha-SMA protein
      expression patterns may aid in distinguishing between VC and VH in challenging
      cases.

PMID- 24560560
TI  - Histologic lichenoid features in oral dysplasia and squamous cell carcinoma.
AB  - OBJECTIVE: This study describes the occurrence of histopathologic characteristics
      of oral lichenoid mucositis in epithelial dysplasia and squamous cell carcinoma.
      STUDY DESIGN: This retrospective review examined 352 histologic specimens of
      group 1 (mild to moderate dysplasia), group 2 (severe dysplasia or carcinoma in
      situ), and group 3 (squamous cell carcinoma) for correlation between 5 histologic
      characteristics frequently found in oral lichen planus and grade, age, gender,
      and oral subsite. RESULTS: In this sample, 29% of all cases exhibited 3 or more
      lichenoid features. Lichenoid features were significantly more frequent in group
      1 over group 2 lesions for cases meeting a minimum lichenoid threshold (P =
      .001). No statistically significant patterns were noted for age or gender. The
      buccal mucosa was significantly overrepresented (P = .039) and the floor of the
      mouth was significantly underrepresented (P = .049) in regard to lichenoid
      feature frequency. CONCLUSIONS: This study confirms the frequent correlation of
      lichenoid characteristics in oral premalignant and malignant lesions.

PMID- 24560558
TI  - Two steps forward, one step back: determining XPD helicase mechanism by single
      molecule fluorescence and high-resolution optical tweezers.
AB  - XPD-like helicases constitute a prominent DNA helicase family critical for many
      aspects of genome maintenance. These enzymes share a unique structural feature,
      an auxiliary domain stabilized by an iron-sulphur (FeS) cluster, and a 5'-3'
      polarity of DNA translocation and duplex unwinding. Biochemical analyses
      alongside two single-molecule approaches, total internal reflection fluorescence
      microscopy and high-resolution optical tweezers, have shown how the unique
      structural features of XPD helicase and its specific patterns of substrate
      interactions tune the helicase for its specific cellular function and shape its
      molecular mechanism. The FeS domain forms a duplex separation wedge and
      contributes to an extended DNA binding site. Interactions within this site
      position the helicase in an orientation to unwind the duplex, control the
      helicase rate, and verify the integrity of the translocating strand. Consistent
      with its cellular role, processivity of XPD is limited and is defined by an
      idiosyncratic stepping kinetics. DNA duplex separation occurs in single base pair
      steps punctuated by frequent backward steps and conformational rearrangements of
      the protein-DNA complex. As such, the helicase in isolation mainly stabilizes
      spontaneous base pair opening and exhibits a limited ability to unwind stable DNA
      duplexes. The presence of a cognate ssDNA binding protein converts XPD into a
      vigorous helicase by destabilizing the upstream dsDNA as well as by trapping the
      unwound strands. Remarkably, the two proteins can co-exist on the same DNA strand
      without competing for binding. The current model of the XPD unwinding mechanism
      will be discussed along with possible modifications to this mechanism by the
      helicase interacting partners and unique features of such bio-medically important
      XPD-like helicases as FANCJ (BACH1), RTEL1 and CHLR1 (DDX11). 

PMID- 24560561
TI  - Assessing the intracellular concentration of platinum in medulloblastoma cell
      lines after Cisplatin incubation.
AB  - Two different analytical approaches, external calibration and isotope dilution
      analysis both using flow-injection inductively coupled plasma mass spectrometry,
      have been developed and applied to determine the intracellular platinum
      concentration after Cisplatin incubation of two different medulloblastoma cell
      lines (UW228 and DAOY). As the internal or isotopically enriched standard was
      already used for cell lysis, maximum accuracy of the results was obtained,
      whereas a new home-built and inert injection system dramatically lowered carry
      over effects and analyte loss. With limits of the detection well below 0.4MUgL(
      1) and typical relative standard deviations of 2%, a strong correlation between
      the cell viability in MTT assays and the incorporated amount of Pt could be
      shown, which was subsequently normalized to the protein content of the samples.
      DAOY cells did significantly ingest more Pt and showed a higher mortality, which
      supports the fact that transporter expression needs to be taken into account in
      order to obtain meaningful results. 

PMID- 24560562
TI  - The relationship between biofilm formations and capsule in Haemophilus
      influenzae.
AB  - To evaluate the biofilm formation of non-typeable Haemophilus influenzae (NTHi)
      and H. influenzae type b (Hib) clinical isolates, we conducted the following
      study. Serotyping and polymerase chain reaction were performed to identify beta
      lactamase-negative ampicillin (ABPC)-susceptible (BLNAS), beta-lactamase-negative
      ABPC-resistant (BLNAR), TEM-1 type beta-lactamase-producing ABPC-resistant
      (BLPAR)-NTHi, and Hib. Biofilm formation was investigated by microtiter biofilm
      assay, as well as visually observation with a scanning electron microscopy (SEM)
      and confocal laser scanning microscopy (CLSM) in a continuous-flow chamber. As a
      result, totally 99 strains were investigated, and were classified into 4 groups
      which were 26 gBLNAS, 22 gBLNAR, 28 gBLPAR-NTHi and 23 Hib strains. The mean
      OD600 in the microtiter biofilm assay of gBLNAS, gBLNAR, gBLPAR-NTHi, and Hib
      strains were 0.57, 0.50, 0.34, and 0.08, respectively. NTHi strains were similar
      in terms of biofilm formations, which were observed by SEM and CLSM. Five Hib
      strains with the alternated type b cap loci showed significantly increased
      biofilm production than the other Hib strains. In conclusion, gBLNAS, gBLNAR, and
      gBLPAR-NTHi strains were more capable to produce biofilms compared to Hib
      strains. Our data suggested that resistant status may not be a key factor but
      capsule seemed to play an important role in H. influenzae biofilm formation.

PMID- 24560563
TI  - In vitro neuraminidase inhibitory activity of four neuraminidase inhibitors
      against influenza virus isolates in the 2011-2012 season in Japan.
AB  - The neuraminidase inhibitors oseltamivir phosphate (Tamiflu(r)), zanamivir
      (Relenza(r)), laninamivir octanoate (Inavir(r)), and peramivir (Rapiacta(r)) have
      been available for the treatment of influenza in Japan since 2010. To assess the
      extent of viral resistance, we measured the 50% inhibitory concentration (IC50)
      of each drug for influenza virus isolates from the 2011-2012 influenza season.
      Specimens were obtained from patients prior to treatment. Viral isolation was
      done using Madine-Darby canine kidney cells, and the type and subtype of
      influenza A(H1N1)pdm09, A(H3N2), or influenza B were determined by RT-PCR using
      type- and subtype-specific primers. The IC50 was determined by a neuraminidase
      inhibition assay using a fluorescent substrate. The lineage of influenza B virus
      was determined by direct sequencing of the hemagglutinin gene. Influenza A(H3N2)
      and influenza B viruses were isolated in 283 and 42 patients, respectively, while
      no influenza A(H1N1)pdm09 virus was isolated. No isolate showed an IC50 value
      exceeding 50 nM for any of the neuraminidase inhibitors. IC50 values for A(H3N2)
      were similar between the 2010-2011 and 2011-2012 seasons. In contrast, the IC50
      values for influenza B viruses in the 2011-2012 season to the four drugs were
      significantly lower than those found in the 2010-2011 season. These results
      indicate that the currently epidemic influenza viruses are susceptible to all
      four neuraminidase inhibitors, with no trend for IC50 values to increase in Japan
      at present.

PMID- 24560564
TI  - Dietary patterns and their associations with age-related macular degeneration:
      the Melbourne collaborative cohort study.
AB  - OBJECTIVE: To evaluate the association between dietary patterns and age-related
      macular degeneration (AMD). DESIGN: Food frequency data were collected from
      Melbourne Collaborative Cohort Study (MCCS) participants at the baseline study in
      1990-1994. During follow-up in 2003-2007, retinal photographs were taken and
      evaluated for AMD. PARTICIPANTS: At baseline, 41514 participants aged 40 to 70
      years and born in Australia or New Zealand (69%), or who had migrated from the
      United Kingdom, Italy, Greece, or Malta (31%) were recruited. Of these, 21132
      were assessed for AMD prevalence at follow-up. METHODS: Principal component
      analysis was used to identify dietary patterns (Factors F1-6) among the food
      items. Logistic regression was used to assess associations of dietary patterns
      with AMD. MAIN OUTCOME MEASURES: Odds ratios (ORs) for early stages and advanced
      AMD in association with dietary patterns. RESULTS: A total of 2508 participants
      (12.8%) had early stages of AMD, and 108 participants (0.6%) had advanced AMD.
      Six factors characterized by predominant intakes of fruits (F1); vegetables (F2);
      grains, fish, steamed or boiled chicken, vegetables, and nuts (F3); red meat
      (F4); processed foods comprising cakes, sweet biscuits, and desserts (F5); and
      salad (F6) were identified. Higher F3 scores were associated with a lower
      prevalence of advanced AMD (fourth vs. first quartile) (OR, 0.49; 95% confidence
      interval [CI], 0.28-0.87), whereas F4 scores greater than the median were
      associated with a higher prevalence of advanced AMD (OR, 1.46; 95% CI, 1.0-2.17).
      CONCLUSIONS: Rather than specific individual food items, these factors represent
      a broader picture of food consumption. A dietary pattern high in fruits,
      vegetables, chicken, and nuts and a pattern low in red meat seems to be
      associated with a lower prevalence of advanced AMD. No particular food pattern
      seemed to be associated with the prevalence of the earliest stages of AMD.

PMID- 24560565
TI  - Re: Dua et al.: Human corneal anatomy redefined: a novel pre-Descemet layer
      (Dua's layer) (Ophthalmology 2013;120:1778-85).

PMID- 24560566
TI  - Clinical and imaging features predictive of orbital granulomatosis with
      polyangiitis and the risk of systemic involvement.
AB  - OBJECTIVE: Granulomatosis with polyangiitis (GPA), previously Wegener's
      granulomatosis, requires prompt diagnosis and systemic review to exclude life
      threatening disease. However, early diagnosis of orbital GPA may be difficult
      because anti-neutrophil cytoplasmic antibody (ANCA) and anti-PR3 antibody
      screening can be negative at presentation and orbital biopsies taken for
      diagnosis may not show the classic features of GPA. This study was designed to
      compare GPA with other causes of orbital inflammation and to identify the
      presenting clinical and imaging features most likely to predict GPA and its
      systemic spread. DESIGN: Retrospective noninterventional comparative case series.
      PARTICIPANTS: A total of 247 patients who had undergone orbital biopsies for
      clinical presentations with orbital inflammation were identified from the
      Institute of Ophthalmology pathology database. METHODS: Patients were divided
      into GPA and non-GPA groups on the basis of their final clinical diagnosis.
      Clinical and imaging features of these 2 groups were compared to determine those
      predictive of GPA, and patients with GPA also had long-term evaluation for
      systemic involvement. MAIN OUTCOME MEASURES: A diagnosis of orbital GPA and
      development of systemic GPA were the main outcome measures. RESULTS: Features
      highly suggestive of GPA were sinonasal symptoms, sinonasal changes, or paranasal
      bone erosion on imaging (P < 0.001). Bony erosion was independent of ANCA status
      or systemic involvement. Twenty-two percent of patients (8/37) with GPA had
      evidence of systemic involvement at presentation, and no patient presenting with
      solely orbital GPA developed later systemic disease over a median follow-up of
      2.7 years. CONCLUSIONS: A high index of suspicion should be maintained for GPA
      when a patient presents with an orbital mass and sinonasal symptoms or imaging
      shows sinonasal involvement or paranasal bone erosion. No patient with solely
      orbital GPA involvement at presentation developed systemic disease, suggesting
      that orbital GPA can remain localized in the long-term.

PMID- 24560567
TI  - Author reply: To PMID 23714320.

PMID- 24560568
TI  - Environmental factors affect the risk of dry eye syndrome in a United States
      veteran population.

PMID- 24560569
TI  - Oncologic outcomes of patients undergoing videoscopic inguinal lymphadenectomy
      for metastatic melanoma.
AB  - BACKGROUND: Open inguinal lymphadenectomy for regionally metastatic melanoma is
      associated with a high wound-related morbidity. Videoscopic inguinal
      lymphadenectomy (VIL) is a minimally invasive approach with fewer wound-related
      complications, yet its adoption has been hindered by a lack of oncologic outcomes
      data. STUDY DESIGN: Data were prospectively collected on all VILs performed for
      melanoma from 2008 to 2012 (n = 40) and compared with a retrospective cohort of
      open superficial inguinal lymphadenectomies from 2005 to 2012 (n = 40).
      Continuous variables were analyzed with Student's t-test, binomial variables with
      chi-square, and survival curves using log-rank comparison. RESULTS: Median follow
      up for patients undergoing VIL was 19.1 months compared with 33.9 months in the
      open inguinal lymphadenectomy group. There were no statistical differences in
      demographics (age, sex, body mass index, smoking status, Charlson comorbidity
      index) or clinicopathologic features (primary site, stage, Breslow depth,
      ulceration). Lymph node yield was similar (VIL, 12.6; open, 14.2; p = 0.131).
      Overall recurrence rates were also similar: 27.5% in the VIL group and 30.0% in
      the open group (p = 0.805). One patient in the VIL group and 2 in the open group
      suffered recurrence in the nodal basin. Although median survival was not reached
      in the VIL group, Kaplan-Meier estimates of disease-free survival (p = 0.226) and
      overall survival (p = 0.308) were similar. In a comprehensive analysis of wound
      complications including infection, skin necrosis, and seroma, patients undergoing
      VIL had markedly less morbidity (VIL, 47.5%; open, 80.0%; p = 0.002).
      CONCLUSIONS: Videoscopic inguinal lymphadenectomy is associated with similar
      oncologic outcomes and markedly reduced wound complications when compared with
      open inguinal lymphadenectomy. The minimally invasive procedure may be the
      preferred method for inguinal lymphadenectomy in melanoma.

PMID- 24560570
TI  - The prognostic significance of age in oropharyngeal squamous cell carcinoma.
AB  - OBJECTIVES: Though the effect of age has been studied in some cancer types, its
      prognostic significance in oropharyngeal squamous cell carcinoma (OPSCC) remains
      controversial. Our purpose is to determine the impact of age at diagnosis on
      overall survival (OS) and disease-specific survival (DSS) in patients with OPSCC.
      If the effect is significant, we aim to clarify the age at which prognosis
      worsens. MATERIALS AND METHODS: 15,978 Patients with OPSCC were identified from
      the Surveillance, Epidemiology, and End Results (SEER) database and separated
      into 10 year age groups. We obtained data on age at diagnosis, primary location,
      race, stage, sex, radiological treatment status, and surgical treatment status.
      Kaplan-Meier methods were used to calculate the OS and DSS for each age group.
      DSS analysis was supported by a Simple Multivariable Cox Proportional Hazard
      Regression of all significant variables studied. RESULTS: Significant
      disadvantage in OS and DSS was found with increasing age. A three-group
      stratification was depicted with the best survival in patients aged 1-44, mildly
      inferior survival in patients aged 45-64, and increasingly worse survival in
      patients 65 and older. Multivariable analysis demonstrated statistically
      significant increases in hazard ratio (HR) after age 65 when compared to ages 1
      64. CONCLUSION: Increasing age after 65 is associated with worsening OS and DSS
      in OPSCC. Poorer prognosis is due to multiple factors, possibly including the
      effects of aging, which make elderly patients more susceptible to the
      pathogenesis of OPSCC.

PMID- 24560571
TI  - Evoked and spontaneous transmission favored by distinct sets of synapses.
AB  - BACKGROUND: Spontaneous "miniature" transmitter release takes place at low rates
      at all synapses. Long thought of as an unavoidable leak, spontaneous release has
      recently been suggested to be mediated by distinct pre- and postsynaptic
      molecular machineries and to have a specialized role in setting up and adjusting
      neuronal circuits. It remains unclear how spontaneous and evoked transmission are
      related at individual synapses, how they are distributed spatially when an axon
      makes multiple contacts with a target, and whether they are commonly regulated.
      RESULTS: Electrophysiological recordings in the Drosophila larval neuromuscular
      junction, in the presence of the use-dependent glutamate receptor (GluR) blocker
      philanthotoxin, indicated that spontaneous and evoked transmission employ
      distinct sets of GluRs. In vivo imaging of transmission using synaptically
      targeted GCaMP3 to detect Ca(2+) influx through the GluRs revealed little spatial
      overlap between synapses participating in spontaneous and evoked transmission.
      Spontaneous and evoked transmission were oppositely correlated with presynaptic
      levels of the protein Brp: synapses with high Brp favored evoked transmission,
      whereas synapses with low Brp were more active spontaneously. High-frequency
      stimulation did not increase the overlap between evoked and spontaneous
      transmission, and instead decreased the rate of spontaneous release from synapses
      that were highly active in evoked transmission. CONCLUSIONS: Although individual
      synapses can participate in both evoked and spontaneous transmission, highly
      active synapses show a preference for one mode of transmission. The presynaptic
      protein Brp promotes evoked transmission and suppresses spontaneous release.
      These findings suggest the existence of presynaptic mechanisms that promote
      synaptic specialization to either evoked or spontaneous transmission.

PMID- 24560572
TI  - Human hippocampus arbitrates approach-avoidance conflict.
AB  - Animal models of human anxiety often invoke a conflict between approach and
      avoidance. In these, a key behavioral assay comprises passive avoidance of
      potential threat and inhibition, both thought to be controlled by ventral
      hippocampus. Efforts to translate these approaches to clinical contexts are
      hampered by the fact that it is not known whether humans manifest analogous
      approach-avoidance dispositions and, if so, whether they share a homologous
      neurobiological substrate. Here, we developed a paradigm to investigate the role
      of human hippocampus in arbitrating an approach-avoidance conflict under varying
      levels of potential threat. Across four experiments, subjects showed analogous
      behavior by adapting both passive avoidance behavior and behavioral inhibition to
      threat level. Using functional magnetic resonance imaging (fMRI), we observe that
      threat level engages the anterior hippocampus, the human homolog of rodent
      ventral hippocampus. Testing patients with selective hippocampal lesions, we
      demonstrate a causal role for the hippocampus with patients showing reduced
      passive avoidance behavior and inhibition across all threat levels. Our data
      provide the first human assay for approach-avoidance conflict akin to that of
      animal anxiety models. The findings bridge rodent and human research on passive
      avoidance and behavioral inhibition and furnish a framework for addressing the
      neuronal underpinnings of human anxiety disorders, where our data indicate a
      major role for the hippocampus.

PMID- 24560573
TI  - Anthropogenic natal environmental effects on life histories in a wild bird
      population.
AB  - Recent work suggests that the environment experienced in early life can alter
      life histories in wild populations, but our understanding of the processes
      involved remains limited. Since anthropogenic environmental change is currently
      having a major impact on wild populations, this raises the possibility that life
      histories may be influenced by human activities that alter environmental
      conditions in early life. Whether this is the case and the processes involved
      remain unexplored in wild populations. Using 23 years of longitudinal data on the
      Mauritius kestrel (Falco punctatus), a tropical forest specialist, we found that
      females born in territories affected by anthropogenic habitat change shifted
      investment in reproduction to earlier in life at the expense of late life
      performance. They also had lower survival rates as young adults. This shift in
      life history strategy appears to be adaptive, because fitness was comparable to
      that of other females experiencing less anthropogenic modification in their natal
      environment. Our results suggest that human activities can leave a legacy on wild
      birds through natal environmental effects. Whether these legacies have a
      detrimental effect on populations will depend on life history responses and the
      extent to which these reduce individual fitness.

PMID- 24560574
TI  - Human-mediated loss of phylogenetic and functional diversity in coral reef
      fishes.
AB  - Beyond the loss of species richness, human activities may also deplete the
      breadth of evolutionary history (phylogenetic diversity) and the diversity of
      roles (functional diversity) carried out by species within communities, two
      overlooked components of biodiversity. Both are, however, essential to sustain
      ecosystem functioning and the associated provision of ecosystem services,
      particularly under fluctuating environmental conditions. We quantified the effect
      of human activities on the taxonomic, phylogenetic, and functional diversity of
      fish communities in coral reefs, while teasing apart the influence of
      biogeography and habitat along a gradient of human pressure across the Pacific
      Ocean. We detected nonlinear relationships with significant breaking points in
      the impact of human population density on phylogenetic and functional diversity
      of parrotfishes, at 25 and 15 inhabitants/km(2), respectively, while parrotfish
      species richness decreased linearly along the same population gradient. Over the
      whole range, species richness decreased by 11.7%, while phylogenetic and
      functional diversity dropped by 35.8% and 46.6%, respectively. Our results call
      for caution when using species richness as a benchmark for measuring the status
      of ecosystems since it appears to be less responsive to variation in human
      population densities than its phylogenetic and functional counterparts,
      potentially imperiling the functioning of coral reef ecosystems.

PMID- 24560575
TI  - Single scale for odor intensity in rat olfaction.
AB  - Humans and laboratory animals are thought to discriminate sensory objects using
      elemental perceptual features computed by neural circuits in the brain. However,
      it is often difficult to identify the perceptual features that animals use to
      make specific comparisons. In olfaction, changes in the concentration of a given
      odor lead to discriminable changes in both its perceived quality and intensity.
      Humans use perceived intensity to compare quantities of different odors. Here we
      establish that laboratory rats also use perceived intensity to compare
      concentrations of different odors and reveal the perceptual organization of this
      elemental feature. We first trained rats to classify concentrations of single
      odors as high or low. When subsequently classifying concentrations of two odors
      presented on different trials of the same session, rats made errors consistent
      with using a single intensity criterion for both odors. This allowed us to
      investigate the relative perceived intensity of different odor pairs. Odor
      intensity was not only a function of concentration, but varied also with
      molecular weight and exposure time. These findings demonstrate the role of
      perceived intensity as an elemental perceptual feature of odors in rat olfaction.

PMID- 24560576
TI  - Homeostatic actin cytoskeleton networks are regulated by assembly factor
      competition for monomers.
AB  - Controlling the quantity and size of organelles through competition for a limited
      supply of components is quickly emerging as an important cellular regulatory
      mechanism. Cells assemble diverse actin filament (F-actin) networks for
      fundamental processes including division, motility, and polarization. F-actin
      polymerization is tightly regulated by activation of assembly factors such as the
      Arp2/3 complex and formins at specific times and places. We directly tested an
      additional hypothesis that diverse F-actin networks are in homeostasis, whereby
      competition for actin monomers (G-actin) is critical for regulating F-actin
      network size. Here we show that inhibition of Arp2/3 complex in the fission yeast
      Schizosaccharomyces pombe not only depletes Arp2/3-complex-mediated endocytic
      actin patches, but also induces a dramatic excess of formin-assembled F-actin.
      Conversely, disruption of formin increases the density of Arp2/3-complex-mediated
      patches. Furthermore, modification of actin levels significantly perturbs the
      fission yeast actin cytoskeleton. Increasing actin favors Arp2/3-complex-mediated
      actin assembly, whereas decreasing actin favors formin-mediated contractile
      rings. Therefore, the specific actin concentration in a cell is critical, and
      competition for G-actin helps regulate the proper amount of F-actin assembly for
      diverse processes.

PMID- 24560577
TI  - FLRT3 is a Robo1-interacting protein that determines Netrin-1 attraction in
      developing axons.
AB  - BACKGROUND: Guidance molecules are normally presented to cells in an overlapping
      fashion; however, little is known about how their signals are integrated to
      control the formation of neural circuits. In the thalamocortical system, the
      topographical sorting of distinct axonal subpopulations relies on the emergent
      cooperation between Slit1 and Netrin-1 guidance cues presented by intermediate
      cellular targets. However, the mechanism by which both cues interact to drive
      distinct axonal responses remains unknown. RESULTS: Here, we show that the
      attractive response to the guidance cue Netrin-1 is controlled by Slit/Robo1
      signaling and by FLRT3, a novel coreceptor for Robo1. While thalamic axons
      lacking FLRT3 are insensitive to Netrin-1, thalamic axons containing FLRT3 can
      modulate their Netrin-1 responsiveness in a context-dependent manner. In the
      presence of Slit1, both Robo1 and FLRT3 receptors are required to induce Netrin-1
      attraction by the upregulation of surface DCC through the activation of protein
      kinase A. Finally, the absence of FLRT3 produces defects in axon guidance in
      vivo. CONCLUSIONS: These results highlight a novel mechanism by which
      interactions between limited numbers of axon guidance cues can multiply the
      responses in developing axons, as required for proper axonal tract formation in
      the mammalian brain.

PMID- 24560578
TI  - Voice-sensitive regions in the dog and human brain are revealed by comparative
      fMRI.
AB  - During the approximately 18-32 thousand years of domestication, dogs and humans
      have shared a similar social environment. Dog and human vocalizations are thus
      familiar and relevant to both species, although they belong to evolutionarily
      distant taxa, as their lineages split approximately 90-100 million years ago. In
      this first comparative neuroimaging study of a nonprimate and a primate species,
      we made use of this special combination of shared environment and evolutionary
      distance. We presented dogs and humans with the same set of vocal and nonvocal
      stimuli to search for functionally analogous voice-sensitive cortical regions. We
      demonstrate that voice areas exist in dogs and that they show a similar pattern
      to anterior temporal voice areas in humans. Our findings also reveal that
      sensitivity to vocal emotional valence cues engages similarly located nonprimary
      auditory regions in dogs and humans. Although parallel evolution cannot be
      excluded, our findings suggest that voice areas may have a more ancient
      evolutionary origin than previously known.

PMID- 24560579
TI  - Olfactory coding in the honeybee lateral horn.
AB  - Olfactory systems dynamically encode odor information in the nervous system.
      Insects constitute a well-established model for the study of the neural processes
      underlying olfactory perception. In insects, odors are detected by sensory
      neurons located in the antennae, whose axons project to a primary processing
      center, the antennal lobe. There, the olfactory message is reshaped and further
      conveyed to higher-order centers, the mushroom bodies and the lateral horn.
      Previous work has intensively analyzed the principles of olfactory processing in
      the antennal lobe and in the mushroom bodies. However, how the lateral horn
      participates in olfactory coding remains comparatively more enigmatic. We studied
      odor representation at the input to the lateral horn of the honeybee, a social
      insect that relies on both floral odors for foraging and pheromones for social
      communication. Using in vivo calcium imaging, we show consistent neural activity
      in the honeybee lateral horn upon stimulation with both floral volatiles and
      social pheromones. Recordings reveal odor-specific maps in this brain region as
      stimulations with the same odorant elicit more similar spatial activity patterns
      than stimulations with different odorants. Odor-similarity relationships are
      mostly conserved between antennal lobe and lateral horn, so that odor maps
      recorded in the lateral horn allow predicting bees' behavioral responses to
      floral odorants. In addition, a clear segregation of odorants based on pheromone
      type is found in both structures. The lateral horn thus contains an odor-specific
      map with distinct representations for the different bee pheromones, a
      prerequisite for eliciting specific behaviors.

PMID- 24560580
TI  - Identification and characterization of lysine-methylated sites on histones and
      non-histone proteins.
AB  - Protein methylation is a kind of post-translational modification (PTM), and
      typically takes place on lysine and arginine amino acid residues. Protein
      methylation is involved in many important biological processes, and most recent
      studies focused on lysine methylation of histones due to its critical roles in
      regulating transcriptional repression and activation. Histones possess highly
      conserved sequences and are homologous in most species. However, there is much
      less sequence conservation among non-histone proteins. Therefore, mechanisms for
      identifying lysine-methylated sites may greatly differ between histones and non
      histone proteins. Nevertheless, this point of view was not considered in previous
      studies. Here we constructed two support vector machine (SVM) models by using
      lysine-methylated data from histones and non-histone proteins for predictions of
      lysine-methylated sites. Numerous features, such as the amino acid composition
      (AAC) and accessible surface area (ASA), were used in the SVM models, and the
      predictive performance was evaluated using five-fold cross-validations. For
      histones, the predictive sensitivity was 85.62% and specificity was 80.32%. For
      non-histone proteins, the predictive sensitivity was 69.1% and specificity was
      88.72%. Results showed that our model significantly improved the predictive
      accuracy of histones compared to previous approaches. In addition, features of
      the flanking region of lysine-methylated sites on histones and non-histone
      proteins were also characterized and are discussed. A gene ontology functional
      analysis of lysine-methylated proteins and correlations of lysine-methylated
      sites with other PTMs in histones were also analyzed in detail. Finally, a web
      server, MethyK, was constructed to identify lysine-methylated sites. MethK now is
      available at http://csb.cse.yzu.edu.tw/MethK/. 

PMID- 24560581
TI  - Alcohol-induced impairment of inhibitory control is linked to attenuated brain
      responses in right fronto-temporal cortex.
AB  - BACKGROUND: A self-enhancing loop between impaired inhibitory control under
      alcohol and alcohol consumption has been proposed as a possible mechanism
      underlying dysfunctional drinking in susceptible people. However, the neural
      underpinnings of alcohol-induced impairment of inhibitory control are widely
      unknown. METHODS: We measured inhibitory control in 50 young adults with a stop
      signal task during functional magnetic resonance imaging. In a single-blind
      placebo-controlled cross-over design, all participants performed the stop-signal
      task once under alcohol with a breath alcohol concentration of .6 g/kg and once
      under placebo. In addition, alcohol consumption was assessed with a free-access
      alcohol self-administration paradigm in the same participants. RESULTS:
      Inhibitory control was robustly decreased under alcohol compared with placebo,
      indicated by longer stop-signal reaction times. On the neural level, impaired
      inhibitory control under alcohol was associated with attenuated brain responses
      in the right fronto-temporal portion of the inhibition network that supports the
      attentional capture of infrequent stop-signals and subsequent updating of action
      plans from response execution to inhibition. Furthermore, the extent of alcohol
      induced impairment of inhibitory control predicted free-access alcohol
      consumption. CONCLUSIONS: We suggest that during inhibitory control alcohol
      affects cognitive processes preceding actual motor inhibition. Under alcohol,
      decreased brain responses in right fronto-temporal areas might slow down the
      attentional capture of infrequent stop-signals and subsequent updating of action
      plans, which leads to impaired inhibitory control. In turn, pronounced alcohol
      induced impairment of inhibitory control might enhance alcohol consumption in
      young adults, which might promote future alcohol problems.

PMID- 24560582
TI  - Disrupted in schizophrenia 1 modulates medial prefrontal cortex pyramidal neuron
      activity through cAMP regulation of transient receptor potential C and small
      conductance K+ channels.
AB  - BACKGROUND: Disrupted in schizophrenia 1 (DISC1) is a protein implicated in
      schizophrenia, bipolar disorder, major depressive disorder, and autism. To date,
      most of research examining DISC1 function has focused on its role in
      neurodevelopment, despite its presence throughout life. DISC1 also regulates
      cyclic adenosine monophosphate (cAMP) signaling by increasing type 4
      phosphodiesterase catabolism of cAMP when cAMP concentrations are high. In this
      study, we tested the hypothesis that DISC1, through its regulation of cAMP,
      modulates I-SK and I-TRPC channel-mediated ionic currents that we have shown
      previously to regulate the activity of mature prefrontal cortical pyramidal
      neurons. METHODS: We used patch-clamp recordings in prefrontal cortical slices
      from adult rats in which DISC1 function was reduced in vivo by short hairpin RNA
      viral knockdown or in vitro by dialysis of DISC1 antibodies. RESULTS: We found
      that DISC1 disruption resulted in an increase of metabotropic glutamate receptor
      induced intracellular calcium (Ca2+) waves, small-conductance K+ (SK)-mediated
      hyperpolarization and a decrease of transient receptor potential C (TRPC)
      mediated sustained depolarization. Consistent with a role for DISC1 in regulation
      of cAMP signaling, forskolin-induced cAMP production also increased intracellular
      Ca2+ waves, I-SK and decreased I-TRPC. Lastly, inhibiting cAMP generation with
      guanfacine, an alpha2A-noradrenergic agonist, normalized the function of SK and
      TRPC channels. CONCLUSIONS: Based on our findings, we propose that diminished
      DISC1 function, such as occurs in some mental disorders, can lead to the
      disruption of normal patterns of prefrontal cortex activity through the loss of
      cAMP regulation of metabotropic glutamate receptor-mediated intracellular Ca2+
      waves, SK and TRPC channel activity.

PMID- 24560583
TI  - A far-upstream AP-1/Smad binding box regulates human NOX4 promoter activation by
      transforming growth factor-beta.
AB  - NADPH oxidase 4 (NOX4) is a member of the NADPH oxidase gene family that
      regulates cellular differentiation, innate immunity and tissue fibrosis.
      Transforming growth factor-beta (TGF-beta1) is known to induce expression of NOX4
      mRNA in mesenchymal cells. However, the mechanisms of transcriptional regulation
      of NOX4 are not well understood. In this study, we examined the transcriptional
      regulation of NOX4 in human lung fibroblasts by TGF-beta1. Five promoter-reporter
      constructs containing DNA fragments of 0.74kb, 1.35kb, 1.84kb, 3.97kb and 4.76kb
      upstream from the transcriptional start site (TSS) of the human NOX4 gene were
      generated and their relative responsiveness to TGF-beta1 analyzed. TGF-beta1
      induced NOX4 gene promoter activation requires a region between -3.97kb and 
      4.76kb. Bioinformatics analysis revealed a 15bp AP-1/Smad binding element in this
      region. Mutation or deletion of either the AP-1 or the Smad element attenuated
      TGF-beta1 responsiveness of the -4.76kb NOX4 promoter. Furthermore, insertion of
      this AP-1/Smad box conferred TGF-beta1 inducibility to the non-responsive -3.97kb
      NOX4 promoter construct. Chromatin immunoprecipitation analysis indicated that
      phospho-Smad3 and cJun associate with this element in a TGF-beta1-inducible
      manner. These results demonstrate that the AP-1/Smad box located between 3.97kb
      and 4.76kb upstream of the TSS site of the NOX4 promoter is essential for NOX4
      gene transcription induced by TGF-beta1 in human lung fibroblasts. Our study
      provides insights into the molecular mechanisms of NOX4 gene expression,
      informing novel therapeutic approaches to interfere with upregulation of NOX4 in
      diseases characterized by activation of the TGF-beta1/NOX4 pathway. 

PMID- 24560584
TI  - [The influence of symbiotics in multi-organ failure: randomised trial].
AB  - BACKGROUND AND OBJECTIVE: To assess whether the administration of symbiotic
      preparations in patients with multi-organ failure (MOF) diminishes the evolution
      of the failure, the inflammatory response generated, the colonization pattern and
      the Intensive Care Unit (ICU) infectious illness. PATIENTS AND METHOD: Randomized
      and controlled trial. All patients with MOF were included. Neutropenia and acute
      pancreatitis patients were excluded. A symbiotic (Simbiotic Drink) was
      administered via enteral feeding during the first 7 days. Variables of interest
      were: Sequential Organ Failure Assessment (SOFA) score evolution, systemic
      concentrations of lactate, fibrinogen and D-dimer; skin and mucosa colonization
      and infectious disease register. RESULTS: Eighty-nine patients were included; 46
      in the symbiotic group (SG) and 43 in the control group (CG). There were 68.5%
      males, with a median age of 69 years. There were no significant differences in
      the patients' fundamental characteristics (medical history, age, reason for
      admission, severity scores), nor in the length of ICU stay or in mortality.
      Comparing the SG with the CG, there were lower lactate levels on the second day,
      more fibrinogen levels on the days 5 and 7, and lower D-dimer levels on the day
      7. Eight hundred and ninety-five cultures were performed for colonization
      assessment, with isolation of 528 microorganisms. No differences in
      microbiological resistance were found; there were more colonization in the SG by
      Candida in mucous membranes after the third day; this situation resolved after
      stopping symbiotic administration. Twenty-two patients suffered an infectious
      disease in ICU, 14 in SG (42.4%) and 19 in CG (57.6%). Although no differences
      were found in the microbiological pattern, there was a predominance of Candida
      spp. over other microorganisms (4 vs. 0 cases). CONCLUSIONS: The symbiotic
      preparation Simbiotic Drink, administered in MOF, results in differences to
      improve the early lactate levels and late fibrinogen/D-dimer levels as well as
      mucosa colonization by Candida. There were no differences in the ICU evolution.

PMID- 24560585
TI  - Outcomes of pancreaticoduodenectomy for pancreatic malignancy in octogenarians:
      an American College of Surgeons National Surgical Quality Improvement Program
      analysis.
AB  - BACKGROUND: Most series analyzing outcomes of pancreaticoduodenectomy in
      octogenarians are limited by a small sample size. The investigators used the
      American College of Surgeons National Surgical Quality Improvement Program
      database for an analysis of the impact of advanced age on outcomes after
      pancreatic cancer surgery. METHODS: The National Surgical Quality Improvement
      Program database from 2005 to 2010 was accessed to study the outcomes of 475
      pancreaticoduodenectomies performed in patients >=80 years of age compared with
      4,102 patients <80 years of age using chi-square and Student's t tests. A
      multivariate logistic regression was used to analyze factors associated with 30
      day mortality and the occurrence of major complications. RESULTS: Octogenarians
      had significantly more preoperative comorbidities compared with patients <80
      years of age. On multivariate analysis, age >=80 years was associated with an
      increased likelihood of experiencing 30-day mortality and major complications
      compared with patients <80 years of age. On subgroup analysis, septuagenarians
      had a similar odds ratio of experiencing mortality or complications compared with
      octogenarians, whereas patients <70 years of age were at lower risk. CONCLUSIONS:
      Although octogenarians have an increased risk for mortality and major
      complications compared with patients <80 years of age, on subgroup analysis, they
      do not differ from septuagenarians.

PMID- 24560586
TI  - Complete cervical spinal cord injury above C6 predicts the need for tracheostomy.
AB  - BACKGROUND: Failed extubation and delayed tracheostomy contribute to poor
      outcomes in patients with a traumatic spinal cord injury (SCI). We determined if
      the level and completeness of SCI predict the need for tracheostomy. METHODS:
      Data from 256 patients with SCI between C1 and T3 with or without tracheostomy
      were retrospectively analyzed. Logistic regression identified predictors for
      tracheostomy. Data are presented as raw percentage or odds ratio (OR) with 95%
      confidence interval. P < .05 indicates significance. RESULTS: Complete spinal
      cord injuries were common in patients requiring tracheostomy (55% vs 18%, P <
      .05), and predicted the need for tracheostomy (OR: 6.4 (3.1 to 13.5), P < .05).
      An injury above C6 predicted the need for tracheostomy in patients with complete
      injury (OR: 3.7 (1 to 11.9), P < .05), but not incomplete injury (OR: .7 (.3 to
      1.9); P = .53). CONCLUSION: Tracheostomy is unlikely in patients with incomplete
      SCI, regardless of the level of injury. Patients with complete SCI above C6 are
      likely to require tracheostomy.

PMID- 24560587
TI  - Biliary obstruction and postoperative morbidity after pancreatoduodenectomy: what
      still obstructs clearance to clearance of obstruction.

PMID- 24560588
TI  - Stafne bone cavities: systematic algorithm for diagnosis derived from
      retrospective data over a 5-year period.
AB  - Stafne bone cavities are usually found in men 50-70 years old. Typically they
      appear as lingual, open, ovoid lesions of the molar region of the lower jaw, and
      most contain parts of the submandibular gland. We have retrospectively examined
      panoramic radiographs acquired over a 5-year period. All lesions suspected of
      being Stafne bone cavities were included and analysed further to retrieve
      statistical information and derive a systematic diagnostic algorithm. We
      identified 21 Stafne bone cavities among 2928 patients (0.7%). Four of these were
      confirmed on cone-beam computed tomography (CT). One patient had magnetic
      resonance imaging (MRI) to confirm the diagnosis. The M:F ratio was 14:7 and the
      mean age 53 years (range 22-82). All cavities were located in the posterior
      mandible, 9 on the right and 12 on the left. The mean length was 10.9 (range 4.5
      23) mm and height 5.7 (range 3.3-17.3) mm. All cavities were located in the
      posterior mandible. Sixteen panoramic radiographs (0.6%) were classified as
      possibly having a Stafne bone cavity but did not fulfil enough criteria to
      confirm the diagnosis. These 16 were not further analysed. It is rare to diagnose
      a Stafne bone cavity on a panoramic radiograph. Thorough investigation is
      essential to exclude differential diagnoses such as keratocystic odontogenic
      tumour, ameloblastoma, or a metastasis. In atypical presentations 3-dimensional
      cone-beam CT is helpful to verify the lingual opening. If the diagnosis is still
      not clear, it can be confirmed by MRI. 

PMID- 24560589
TI  - Molecular characterization of a duck hepatitis virus 3-like astrovirus.
AB  - Using an ORF1b-based astrovirus-specific reverse transcription (RT)-PCR assay, a
      duck hepatitis virus type 3 (DHV-3)-like astrovirus was detected from four
      intestinal samples collected from diseased ducks in China. Complete genome
      sequencing and comparative sequence analysis showed that the four duck astrovirus
      (DAstV) isolates were closely related and possessed a typical astrovirus genome
      organization. Genetic analysis of the complete ORF2 region revealed that mean
      amino acid genetic distances between the DHV-3-like isolates and previously known
      avastrovirus species were between 0.579 and 0.721, suggesting that the DHV-3-like
      isolates could be classified as an additional avastrovirus species. In the ORF1a
      and ORF1b regions, however, mean amino acid genetic distances between the DHV-3
      like viruses and the turkey astrovirus 2 (TAstV-2)-like isolates were
      substantially less than those between TAstV-2-like isolates and DAstV/C-NGB-like
      astroviruses belonging to the same species. Pairwise comparisons and phylogenetic
      analyses demonstrated that the DHV-3-like isolates were most closely related to
      TAstV-2-like viruses in ORF1a and ORF1b, while showed highest similarity with the
      chicken astrovirus (CAstV) 612-like viruses in ORF2. These findings provide
      evidence that recombination events may have occurred during evolution of the
      avastroviruses and support the view that genomic analysis is required for
      classification of the avastroviruses. 

PMID- 24560590
TI  - Salmonella serotypes in reptiles and humans, French Guiana.
AB  - In French Guiana, a French overseas territory located in the South American
      northern coast, nearly 50% of Salmonella serotypes isolated from human infections
      belong to serotypes rarely encountered in metropolitan France. A reptilian source
      of contamination has been investigated. Between April and June 2011, in the area
      around Cayenne, 151 reptiles were collected: 38 lizards, 37 snakes, 32 turtles,
      23 green iguanas and 21 caimans. Cloacal swab samples were collected and
      cultured. Isolated Salmonella strains were identified biochemically and
      serotyped. The overall carriage frequency of carriage was 23.2% (95% confidence
      interval: 16.7-30.4) with 23 serotyped strains. The frequency of Salmonella
      carriage was significantly higher for wild reptiles. Near two-thirds of the
      Salmonella serotypes isolated from reptiles were also isolated from patients in
      French Guiana. Our results highlight the risk associated with the handling and
      consumption of reptiles and their role in the spread of Salmonella in the
      environment. 

PMID- 24560591
TI  - Detection of Shiga toxigenic (STEC) and enteropathogenic (EPEC) Escherichia coli
      in dairy buffalo.
AB  - Enteropathogenic (EPEC) and Shiga toxigenic (STEC) Escherichia coli are among the
      bacteria most associated with enteric diseases in man. The aims of this study
      were to determine the prevalence of STEC and EPEC in dairy buffalo and then
      characterize these isolates genetically. To determine the prevalence of these
      bacteria, samples were collected from the feces and milk of buffaloes. In total,
      256 samples were collected in 3 samplings, of which 76 samples tested positive
      for either the stx1, stx2 or eae genes or a combination thereof. From the
      positive samples, 22 STEC and 11 atypical EPEC (aEPEC) isolates were obtained.
      The isolates showed 23 different genetic profiles. No profile was very frequent
      in STEC isolates. On the other hand, the profile eae+, ehxA+, iha+, efa1+, toxB+,
      paa+, lpfAO113+ was found in 45% of the aEPEC isolates. In addition to stx1, stx2
      and eae, the genes ehxA, efa1, saa, lpfAO113, lpfAO157/OI-141, lpfAO157/OI-154,
      toxB and iha were present in the isolates. Serogroup O26 was found in 26% of the
      aEPEC. Other serogroups detected include O87, O145, O176 and O179. The isolates
      were sensitive to almost all drugs tested and some isolates shared the same
      fingerprint patterns by enterobacterial repetitive intergenic consensus sequence
      PCR (ERIC-PCR). The results suggest that, besides major reservoirs of STEC,
      buffaloes are also aEPEC reservoirs. The detection of a serogroup (O26), and
      putative virulence genes (efa1 ehxA, paa and lpfAO113), previously associated
      with aEPEC isolated from humans with diarrhea in aEPEC from buffaloes should be
      studied further.

PMID- 24560592
TI  - Innate immune responses of airway epithelial cells to infection with equine
      herpesvirus-1.
AB  - Equine herpesvirus-1 (EHV-1) is the cause of respiratory disease, abortion and
      myelitis in horses worldwide. Protection following infection or vaccination is
      typically incomplete and this lack of protective immunity is thought to be due to
      the immunomodulatory properties of EHV-1. EHV-1 immune modulation is likely
      initiated early in the infection cycle at the respiratory epithelium, but to
      date, immunity to EHV-1 at the epithelial cell barrier remains poorly
      characterized. Thus, the purpose of this study was to use a recently established
      primary equine respiratory epithelial cell culture (EREC) system to characterize
      innate immunity to EHV-1. Differentiated ERECs were inoculated with a
      neuropathogenic strain of EHV-1 and cytokine responses were determined using
      quantitative real-time polymerase chain reaction and ELISA. Major
      histocompatibility complex (MHC)-I and MHC-II as well as toll-like receptor
      (TLR)3 and TLR9 protein expression were examined using fluorescence activated
      cell-sorting analysis and chemotaxis of neutrophils and monocytes were evaluated
      using chemotaxis assays. Infection with EHV-1 resulted in increased expression of
      TLR3 and 9 as well as inflammatory cytokines (IL-1, TNF-alpha, IFN-alpha, and IL
      6) and chemokines (IL-8, MCP-1). In contrast, EHV-1 infection caused marked
      decreases of MHC-I and MHC-II expression as well as a reduction in IFN-gamma
      production. In summary, these results provide an initial characterization of the
      early immune response to EHV-1 at the epithelial cell barrier and show that,
      while EHV-1 maintains induction of an inflammatory response, it causes an
      attenuation of IFN-gamma responses and down-modulates expression of MHC-I and MHC
      II, which are important molecules for antigen presentation. 

PMID- 24560593
TI  - Chlamydial infections of fish: diverse pathogens and emerging causes of disease
      in aquaculture species.
AB  - Chlamydial infections of fish are emerging as an important cause of disease in
      new and established aquaculture industries. To date, epitheliocystis, a skin and
      gill disease associated with infection by these obligate intracellular pathogens,
      has been described in over 90 fish species, including hosts from marine and fresh
      water environments. Aided by advances in molecular detection and typing, recent
      years have seen an explosion in the description of these epitheliocystis-related
      chlamydial pathogens of fish, significantly broadening our knowledge of the
      genetic diversity of the order Chlamydiales. Remarkably, in most cases, it seems
      that each new piscine host studied has revealed the presence of a
      phylogenetically unique and novel chlamydial pathogen, providing researchers with
      a fascinating opportunity to understand the origin, evolution and adaptation of
      their traditional terrestrial chlamydial relatives. Despite the advances in this
      area, much still needs to be learnt about the epidemiology of chlamydial
      infections in fish if these pathogens are to be controlled in farmed
      environments. The lack of in vitro methods for culturing of chlamydial pathogens
      of fish is a major hindrance to this field. This review provides an update on our
      current knowledge of the taxonomy and diversity of chlamydial pathogens of fish,
      discusses the impact of these infections on the health, and highlights further
      areas of research required to understand the biology and epidemiology of this
      important emerging group of fish pathogens of aquaculture species. 

PMID- 24560594
TI  - Cross-talk between liver and intestine in control of cholesterol and energy
      homeostasis.
AB  - A major hurdle for organisms to dispose of cholesterol is the inability to
      degrade the sterol nucleus which constitutes the central part of the molecule.
      Synthesis of the sterol nucleus requires a complex, energy costly, metabolic
      pathway but also generates a diverse array of intermediates serving crucial roles
      in cellular energy metabolism and signal transduction. This may be the reason why
      this complex pathway has survived evolutionary pressure. The only way to get rid
      of substantial amounts of cholesterol is conversion into bile acid or direct
      excretion of the sterol in the feces. The lack of versatility in disposal
      mechanisms causes a lack of flexibility to regulate cholesterol homeostasis which
      may underlie the considerable human pathology linked to cholesterol removal from
      the body. Export of cholesterol from the body requires an intricate communication
      between intestine and the liver. The last decade this inter-organ cross talk has
      been focus of intense research leading to considerable new insight. This novel
      information on particular the cross-talk between liver and intestine and role of
      bile acids as signal transducing molecules forms the focus of this review. 

PMID- 24560595
TI  - Fluctuations in the DNA double helix: A critical review.
AB  - A critical overview of the extensive literature on fluctuations in the DNA double
      helix is presented. Both theory and experiment are comprehensively reviewed and
      analyzed. Fluctuations, which open up the DNA double helix making bases
      accessible for hydrogen exchange and chemical modification, are the main focus of
      the review. Theoretical descriptions of the DNA fluctuations are discussed with
      special emphasis on most popular among them: the nonlinear-dynamic Peyrard-Bishop
      Dauxois (PBD) model and the empirical two-state (or helix-coil) model. The
      experimental data on the issue are comprehensibly overviewed in the historical
      retrospective with main emphasis on the hydrogen exchange data and formaldehyde
      kinetics. The theoretical descriptions are critically evaluated from the
      viewpoint of their applicability to describe DNA in water environment and from
      the viewpoint of agreement of their predictions with the reliable experimental
      data. The presented analysis makes it possible to conclude that, while the two
      state model is most adequate from theoretical viewpoint and its predictions,
      based on an empirical parametrization, agree with experimental data very well,
      the PBD model is inapplicable to DNA in water from theoretical viewpoint on one
      hand and it makes predictions totally incompatible with reliable experimental
      data on the other. In particular, it is argued that any oscillation movements of
      nucleotides, assumed by the PBD model, are severely damped in water, that no
      "bubbles", which the PBD model predicts, exist in reality in linear DNA well
      below the melting range and the lifetime of an open state in DNA is actually 5
      orders of magnitude longer than the value predicted by the PBD model.

PMID- 24560596
TI  - Radioguided surgery in Meckel's diverticulum.
AB  - We analyze the case of a patient with intermittent episodes of lower
      gastrointestinal bleeding and suspected Meckel's diverticulum, whose presence was
      confirmed by (99m)Tc-pertechnetate scintigraphy. A previous exploratory
      laparotomy had been performed without finding the diverticulum. In spite of years
      of medical treatment, the patient presented a new episode of lower
      gastrointestinal bleeding with normal colonoscopy. A new (99m)Tc-pertechnetate
      scintigraphy (including SPECT/CT) was performed and allowed the anatomical
      location of a Meckel's diverticulum and enabled its removal by laparoscopic
      radioguided surgery. The introduction of SPECT/CT in the scintigraphic diagnostic
      protocol in Meckel's diverticulum increases diagnostic safety and improves lesion
      location. Furthermore, it favors the performance of radioguided surgery and
      facilitates the lesion resection, particularly when the patient has suffered
      previous abdominal surgery, with a more conservative procedure, reducing the
      morbidity associated with the surgical procedure.

PMID- 24560597
TI  - [Interpretation of thyroid incidentalomas in (18)F-FDG PET/CT studies].
AB  - OBJECTIVE: Thyroid findings or incidentalomas in (18)F-FDG PET/CT studies are
      relatively frequent, being its clinical significance subject of controversy. The
      aim of this study was to show our experience in the detection of thyroid
      incidentalomas by PET/CT studies as well as its follow up. MATERIAL AND METHODS:
      A retrospective and descriptive review was conducted on patients who had thyroid
      incidentalomas detected in (18)F-FDG PET/CT studies between June 2010 and March
      2013. Patient's medical records were reviewed for age, genre, maximum
      standardized uptake value (SUVmax), thyroid diseases, TSH and antithyroid
      antibodies levels, ultrasound, fine-needle aspiration (FNA) and cytology.
      RESULTS: 4085 PET/CT studies for several purposes were performed. Eighty-three of
      these studies (2.03%) showed thyroid incidentalomas. Thirty-seven patients showed
      a diffuse increase of glucose metabolism in the thyroid gland and 46 showed a
      focal increase of glucose metabolism. Five out of 46 patients with focal uptake
      were diagnosed of a neoplastic disease by cytology (11%). The SUVmax of malignant
      pathology did not differ from that of benign thyroid diseases (Mean: 10,26 and
      5,92 respectively). CONCLUSION: In our experience, focal thyroid incidentalomas
      detected in (18)F-FDG PET/CT studies are related to a significant risk of
      malignancy (11%). Therefore, in these situations, an ultrasound study with fine
      needle biopsy should be recommended. Moreover, a diffuse increase of glucose
      metabolism in the thyroid gland is often associated with benign thyroid
      pathology.

PMID- 24560598
TI  - [Selective biopsy of the sentinel lymph node in breast cancer: without axillary
      recurrences after a mean follow-up of 4.5 years].
AB  - OBJECTIVE: To analyze the rate of axillary recurrences (AR) in patients with
      early breast cancer who had not undergone an axillary node dissection (ALND)
      because of a negative sentinel lymph node biopsy (SLNB). MATERIAL AND METHODS:
      The study includes 173 patients operated on for breast cancer and selective node
      biopsy. In 32 patients the SLNB was positive and undergone subsequent ALND. We
      followed up 141 patients with negative SLNB without LDN, with a median follow up
      of 55 months (range 74-36). RESULTS: The detection rate of SLN was of 99.42%.
      After a median follow-up of 4.5 years, there were no axillary recurrences. Two
      patients developed local recurrence, other two patients developed distant
      metastases and four patients developed a metachronous tumor. Four patients died,
      none of them because of breast cancer. CONCLUSIONS: The results obtained support
      the SLNB as an accurate technique in the axillary stratification of patients with
      breast cancer, offering in the cases of negative SLNB a safe axillary control
      after 4.5 year follow-up.

PMID- 24560599
TI  - [Presence of Nuclear Medicine in the Spanish journals of Internal Medicine and
      other specialties (2000-2009)].
AB  - OBJECTIVE: This article aims to provide a quantitative and qualitative
      description of the publications on Nuclear Medicine (NM) in journals from other
      disciplines, between 2000 and 2009. MATERIAL AND METHODS: A retrospective
      descriptive study was carried out including the years 2000-2009 in three internal
      medicine journals (IM) and in three related specialty journals (RS). The criteria
      used are that some of the authors were located professionally in a Service, Unit
      or Central MN and/or that the title of the article or at least its content made a
      reference to some specific aspect of NM. Date of publication, the magazine
      section, thematic, data of the authors, province and referral hospital were
      collected. RESULTS: A total of 186 articles were found, 81 in IM journals and 105
      in RS. The IM journal articles came from 43 different hospitals. Vall d'Hebron
      (Barcelona, Spain) was the hospital with the largest volume. Twenty-four
      provinces were identified, Barcelona and Madrid standing out among them with 20
      and 17 articles, respectively. In the RS journals, 59 hospitals/centers had
      participated, Vall d'Hebron standing out with 51 articles. There were 9 foreign
      articles. The articles were distributed into 19 provinces, Barcelona and Madrid
      standing out with 32 papers and 20 papers, respectively. CONCLUSIONS: There are
      at least twice as many articles in the RS Journals than in the IM ones.
      "Original" articles are the most frequent. The Clinical and Translational
      Oncology journal in RS and Medicina Clinica in IM stand out with the highest
      number of articles. No specific topic prevailed.

PMID- 24560600
TI  - The spiral axis as a clinical tool to distinguish essential tremor from dystonia
      cases.
AB  - BACKGROUND: Tremor is a common feature of a variety of neurological disorders. In
      genetic studies of essential tremor (ET), investigators need to screen potential
      enrollees by mail or telephone to exclude those with other neurological
      conditions, especially dystonia. In clinical settings, the differentiation of ET
      and dystonia may also be very challenging. We hypothesized that the spiral axis,
      described below, is a useful screening tool to distinguish ET cases from dystonia
      cases. METHODS: We analyzed the hand-drawn spirals of 135 individuals enrolled in
      a genetics study at Columbia University Medical Center. Each of the four spirals
      was assessed for the presence of a single identifiable tremor orientation axis,
      and a spiral axis score (range = 0-4) [a single axis on all 4 spirals] was
      assigned to each enrollee. RESULTS: There were 120 ET cases and 15 cases with
      dystonic tremor. Most (101/120, 84.2%) ET cases had an axis score >=1 vs. only
      half (8/15, 53.3%) of the dystonia cases (p = 0.02). Receiver Operator Curve
      (ROC) analysis revealed that the use of a spiral axis score >=2 as a cut off
      would exclude 60.0% of dystonia cases while including 67.5% of ET cases.
      CONCLUSION: Handwritten spirals appear to have a single predominant axis in more
      ET than dystonia cases. The evaluation of this axis has moderate diagnostic
      validity as a screening tool to distinguish ET cases from those with dystonia.
      Although this study did not assess the utility of this tool in clinical practice
      settings, future studies should do so.

PMID- 24560602
TI  - Icilin reduces voltage-gated calcium channel currents in naive and injured DRG
      neurons in the rat spinal nerve ligation model.
AB  - Recently, the transient receptor potential (TRP) channels TRPM8 and TRPA1 have
      been identified as molecular sensors for cold, and it has been suggested that
      they play a crucial role in allodynia by modulating voltage-gated calcium channel
      currents (ICa(V)). The aim of this study was to analyze the modulation of ICa(V)
      by the TRPM8-agonist icilin in vitro and to investigate the analgesic effect of
      icilin in a neuropathic pain model in vivo. Whole cell patch-clamp recordings
      were performed on isolated naive and injured rat dorsal root ganglia (DRG)
      neurons, and the analgesic efficacy of icilin applied topically to the paws or
      intrathecally was tested in rats after spinal nerve ligation (SNL). ICa(V)
      (depolarization from -80 to 0mV) in naive DRG neurons was reduced dose
      dependently (0.002-200uM) by icilin (18-80%). Subtype isolation of calcium
      channels show a marked reduction of L-type channel currents compared to N-type
      channel currents. The effects of icilin on ICa(V) were not significantly
      different in non-injured and SNL-injured DRG neurons. In vivo, neither topical
      (10-200uM) nor intrathecal application of icilin (0.1nM to 1uM) affected tactile
      allodynia or thermal hyperalgesia after SNL, but it increases cold allodynia 6h
      after application. We conclude that the icilin-induced modulation of ICa(V) in
      DRG neurons is unlikely to mediate analgesic effects or contribute directly to
      the pathogenesis of cold allodynia in the rat SNL model, but it is a potential
      mechanism for the analgesic effects of icilin in other pain models. 

PMID- 24560601
TI  - Melatonin inhibits voltage-sensitive Ca(2+) channel-mediated neurotransmitter
      release.
AB  - Melatonin is involved in various neuronal functions such as circadian rhythmicity
      and thermoregulation. Melatonin has a wide range of pharmacologically effective
      concentration levels from the nanomolar to millimolar levels. Recently, the
      antiepileptic effect of high dose melatonin has been the focus of clinical
      studies; however, its detailed mechanism especially in relation to
      neurotransmitter release and synaptic transmission remains unclear. We studied
      the effect of melatonin at high concentrations on the neurotransmitter release by
      monitoring norepinephrine release in PC12 cells, and excitatory postsynaptic
      potential in rat hippocampal slices. Melatonin inhibits the 70mM K(+)-induced
      Ca(2+) increase at millimolar levels without effect on bradykinin-triggered
      Ca(2+) increase in PC12 cells. Melatonin (1mM) did not affect A2A adenosine
      receptor-evoked cAMP production, and classical melatonin receptor antagonists did
      not reverse the melatonin-induced inhibitory effect, suggesting G-protein coupled
      receptor independency. Melatonin inhibits the 70mM K(+)-induced norepinephrine
      release at a similar effective concentration range in PC12 cells. We confirmed
      that melatonin (100uM) inhibits excitatory synaptic transmission of the
      hippocampal Schaffer collateral pathway with the decrease in basal synaptic
      transmission and the increase in paired pulse ratio. These results show that
      melatonin inhibits neurotransmitter release through the blocking of voltage
      sensitive Ca(2+) channels and suggest a possible mechanism for the antiepileptic
      effect of melatonin. 

PMID- 24560603
TI  - Berberine was neuroprotective against an in vitro model of brain ischemia:
      survival and apoptosis pathways involved.
AB  - Berberine is an alkaloid derived from herb the Berberis sp. and has long-term use
      in Oriental medicine. Studies along the years have demonstrated its beneficial
      effect in various neurodegenerative and neuropsychiatric disorders. The subject
      of this study was to evaluate whether berberine protects against delayed neuronal
      cell death in organotypic hippocampal culture (OHC) exposed to oxygen and glucose
      deprivation (OGD) and the cell signaling mechanism related to its effect.
      Hippocampal slices were obtained from 6 to 8-days-old male Wistar rat and
      cultured for 14 days. Following, the cultures were exposed for 1h to OGD and then
      treated with Berberine (10 and 20MUM). After 24h recovery, propidium iodide (PI)
      uptake was analyzed and a decrease was observed in PI uptake on OGD Ber-treated
      culture, which means a decrease in cellular death. Western blot analysis showed
      that proteins Akt, GSK3beta, ERK and JNK appear to play a role in berberine
      mediated neuroprotection. Furthermore, capase-3 activity of OGD Ber-treated
      culture was diminished by control level in a fluorimetry assay. These findings
      suggest that berberine-mediated neuroprotection after ischemia involves
      Akt/GSK3beta/ERK 1/2 survival/apoptotic signaling pathway as well as JNK and
      caspase-3 activity inhibition. 

PMID- 24560604
TI  - Use of a systems model of drug-induced liver injury (DILIsym((r))) to elucidate
      the mechanistic differences between acetaminophen and its less-toxic isomer,
      AMAP, in mice.
AB  - Acetaminophen (APAP) has been used as a probe drug to investigate drug-induced
      liver injury (DILI). In mice, 3'-hydroxyacetanilide (AMAP), a less-toxic isomer
      of APAP, has also been studied as a negative control. Various mechanisms for the
      divergence in toxicological response between the two isomers have been proposed.
      This work utilized a mechanistic, mathematical model of DILI to test the
      plausibility of four mechanistic hypotheses. Simulation results were compared to
      an array of measured endpoints in mice treated with APAP or AMAP. The four
      hypotheses included: (1) quantitative differences in drug metabolism profiles as
      a result of different affinities for the relevant enzymes; (2) differences in the
      amount of reactive metabolites produced due to cytochrome P450 (CYP450)
      inhibition by the AMAP reactive metabolites; (3) differences in the rate of
      conjugation between the reactive metabolites and proteins; (4) differences in the
      downstream effects or potencies of the reactive metabolites on vital components
      within hepatocytes. The simulations did not support hypotheses 3 or 4 as the most
      likely hypotheses underlying the difference in hepatoxic potential of APAP and
      AMAP. Rather, the simulations supported hypotheses 1 and 2 (less reactive
      metabolite produced per mole of AMAP relative to APAP). Within the simulations,
      the difference in reactive metabolite formation was equally likely to have
      occurred from differential affinities for the relevant drug metabolism enzymes or
      from direct CYP450 inhibition by the AMAP reactive metabolite. The demonstrated
      method of using simulation tools to probe the importance of possible contributors
      to toxicological observations is generally applicable across species. 

PMID- 24560605
TI  - Multi-element distribution profile in Sprague-Dawley rats: effects of
      intratracheal instillation of Cr(VI) and Zn intervention.
AB  - Our previous epidemiological study revealed that co-exposure of [Cr(VI)] with
      small amount of heavy metals could induce peripheral blood element imbalance, but
      little was known about the contribution of Cr(VI) itself and the multi-element
      distribution profile in other target tissues. We explored element homeostasis in
      the blood, RBC, serum and lung after Cr(VI) exposure and Zn intervention. 60
      Sprague-Dawley male rats received intratracheal instillation of Cr(VI) (0, 0.063,
      0.630mgCr/kg) weekly and/or intragastric administration of zinc sulfate (0,
      10mgZn/kg) daily for one month. Element contents and urinary 8-hydroxy-2'
      deoxyguanosine (8-OHdG) concentrations were determined. Dose-response
      relationship was observed among rats exposed to Cr(VI). Ca, Mg, Mn in the blood,
      Fe, Mg, Se in the serum, and Mg and Zn in lung tissue decreased significantly,
      while Ca, Co, Cr, Mg, Mn, Se in RBC, and Ca, Co, Mo in the lung increased after
      Cr(VI) exposure. The alteration trends manifested differently, with RBC the most
      sensitive. Cr induced increase of urinary 8-OHdG, which decreased after Zn
      intervention. Zn intervention could help to restore element homeostasis after
      Cr(VI) exposure, especially for Ca, Fe, Mg and Se. 

PMID- 24560606
TI  - Binding specificity of retinal analogs to photoactivated visual pigments suggest
      mechanism for fine-tuning GPCR-ligand interactions.
AB  - 11-cis-retinal acts as an inverse agonist stabilizing the inactive conformation
      of visual pigments, and upon photoactivation, it isomerizes to all-trans-retinal,
      initiating signal transduction. We have analyzed opsin regeneration with retinal
      analogs for rhodopsin and red cone opsin. We find differential binding of the
      analogs to the receptors after photobleaching and a dependence of the binding
      kinetics on the oligomerization state of the protein. The results outline the
      sensitivity of retinal entry to the binding pocket of visual receptors to the
      specific conformation adopted by the receptor and by the molecular architecture
      defined by specific amino acids in the binding pocket and the retinal entry site,
      as well as the topology of the retinal analog. Overall, our findings highlight
      the specificity of the ligand-opsin interactions, a feature that can be shared by
      other G-protein-coupled receptors. 

PMID- 24560607
TI  - Structure-guided design of fluorescent S-adenosylmethionine analogs for a high
      throughput screen to target SAM-I riboswitch RNAs.
AB  - Many classes of S-adenosylmethionine (SAM)-binding RNAs and proteins are of
      interest as potential drug targets in diverse therapeutic areas, from infectious
      diseases to cancer. In the former case, the SAM-I riboswitch is an attractive
      target because this structured RNA element is found only in bacterial mRNAs and
      regulates multiple genes in several human pathogens. Here, we describe the
      synthesis of stable and fluorescent analogs of SAM in which the fluorophore is
      introduced through a functionalizable linker to the ribose. A Cy5-labeled SAM
      analog was shown to bind several SAM-I riboswitches via in-line probing and
      fluorescence polarization assays, including one from Staphylococcus aureus that
      controls the expression of SAM synthetase in this organism. A fluorescent ligand
      displacement assay was developed and validated for high-throughput screening of
      compounds to target the SAM-I riboswitch class. 

PMID- 24560609
TI  - Rates, levels, and determinants of electronic health record system adoption: a
      study of hospitals in Riyadh, Saudi Arabia.
AB  - OBJECTIVE: Outside a small number of OECD countries, little information exists
      regarding the rates, levels, and determinants of hospital electronic health
      record (EHR) system adoption. This study examines EHR system adoption in Riyadh,
      Saudi Arabia. MATERIALS AND METHODS: Respondents from 22 hospitals were surveyed
      regarding the implementation, maintenance, and improvement phases of EHR system
      adoption. Thirty-seven items were graded on a three-point scale of
      preparedness/completion. Measured determinants included hospital size, level of
      care, ownership, and EHR system development team composition. RESULTS: Eleven of
      the hospitals had implemented fully functioning EHR systems, eight had systems in
      progress, and three had not adopted a system. Sixteen different systems were
      being used across the 19 adopting hospitals. Differential adoption levels were
      positively related to hospital size and negatively to the level of care
      (secondary versus tertiary). Hospital ownership (nonprofit versus private) and
      development team composition showed mixed effects depending on the particular
      adoption phase being considered. DISCUSSION: Adoption rates compare favourably
      with those reported from other countries and other districts in Saudi Arabia, but
      wide variations exist among hospitals in the levels of adoption of individual
      items. General weaknesses in the implementation phase concern the legacy of paper
      data systems, including document scanning and data conversion; in the maintenance
      phase concern updating/maintaining software; and in the improvement phase concern
      the communication and exchange of health information. CONCLUSION: This study is
      the first to investigate the level and determinants of EHR system adoption for
      public, other nonprofit, and private hospitals in Saudi Arabia. Wide
      interhospital variations in adoption bear implications for policy-making and
      funding intervention. Identified areas of weakness require action to increase the
      degree of adoption and usefulness of EHR systems.

PMID- 24560608
TI  - Mechanisms of self-resistance in the platensimycin- and platencin-producing
      Streptomyces platensis MA7327 and MA7339 strains.
AB  - Platensimycin (PTM) and platencin (PTN) are potent inhibitors of bacterial fatty
      acid synthases and have emerged as promising antibacterial drug leads. We
      previously characterized the PTM and PTN biosynthetic machineries in the
      Streptomyces platensis producers. We now identify two mechanisms for PTM and PTN
      resistance in the S. platensis producers-the ptmP3 or ptnP3 gene within the PTM
      PTN or PTN biosynthetic cluster and the fabF gene within the fatty acid synthase
      locus. PtmP3/PtnP3 and FabF confer PTM and PTN resistance by target replacement
      and target modification, respectively. PtmP3/PtnP3 also represents an
      unprecedented mechanism for fatty acid biosynthesis in which FabH and FabF are
      functionally replaced by a single condensing enzyme. These findings challenge the
      current paradigm for fatty acid biosynthesis and should be considered in future
      development of effective therapeutics targeting fatty acid synthase. 

PMID- 24560610
TI  - Communicating by touch--neurons are not alone.
AB  - Long-distance cell-cell communication is essential for organ development and
      function. Whereas neurons communicate at long distances by transferring signals
      at sites of direct contact (i.e., at synapses), it has been presumed that the
      only way other cell types signal is by dispersing signals through extracellular
      fluid--indirectly. Recent evidence from Drosophila suggests that non-neuronal
      cells also exchange signaling proteins at sites of direct contact, even when long
      distances separate the cells. We review here contact-mediated signaling in
      neurons and discuss how this signaling mechanism is shared by other cell types.

PMID- 24560611
TI  - High prevalence of Human Herpesvirus 8 in schizophrenic patients.
AB  - Many studies have reported an association between Herpes family viruses and an
      increased risk of schizophrenia, but the role of Human Herpesvirus 8 (HHV8) has
      never been investigated. This study aimed to assess HHV8 prevalence in
      schizophrenic patients as well as the possible association between HHV8 infection
      and schizophrenia clinical features. We consecutively enrolled 108 patients
      meeting fourth edition of Diagnostic and Statistical Manual of Mental Disorders
      (DSM-IV) criteria of schizophrenia and 108 age and sex matched controls. Data
      about a number of demographic characteristics and potential HHV8 risk factors of
      infection were collected. Standardized psychopathology measures, disease severity
      and functioning level were obtained using Positive and Negative Syndrome Scale
      (PANSS), Brief Psychiatric Rating Scale (BPRS), Scale for the Assessment of
      Negative Symptoms (SANS), Scale for the Assessment of Positive Symptoms (SAPS),
      Clinical Global Impressions (CGI) and Global Assessment of functioning (GAF). The
      presence of anti-HHV8 antibodies was analyzed using an indirect
      immunofluorescence assay. A higher prevalence of HHV8 infection in schizophrenic
      patients than in controls was found. Marital status, having children, sexual
      behavior and risk factors of blood transmission were not associated with HHV8
      prevalence. However, among schizophrenic patients, HHV8 prevalence was statically
      associated with positive symptoms. To our knowledge, this would be the first
      report of a possible role of HHV8 in the pathogenesis of schizophrenia. To prove
      this hypothesis, further investigation of HHV8 in schizophrenia with larger
      samples is needed. 

PMID- 24560612
TI  - Correlates of insight with symptomatology and executive function in patients with
      first-episode schizophrenia-spectrum disorder: a longitudinal perspective.
AB  - The present study aimed to examine the relationships of insight with
      symptomatology and executive function, both cross-sectionally and longitudinally
      in patients with first-episode schizophrenia-spectrum disorders. Ninety-two
      medication-naive patients were recruited and 71 completed the assessments.
      Insight, symptoms and executive function were assessed at baseline, 6 months and
      1 year. Insight was measured with the abridged version of Scale of Unawareness of
      Mental Disorder (SUMD). Symptoms were assessed using the Positive and Negative
      Syndrome Scale (PANSS). Executive function was measured with the Modified
      Wisconsin Card Sorting Test (MCST). The most significant improvement of insight
      and symptomatology was found over the first 6 months, whereas the perseverative
      errors of MCST were significantly improved between 6 and 12 months. Differential
      correlations of perseverative errors of the MCST and PANSS scores with SUMD were
      found at different time points. This suggests the involvement of different
      mechanisms in insight deficit at different stages of the illness. The baseline
      MCST perseverative errors were correlated significantly with the SUMD total score
      at 6 months and the change of SUMD scores over the first 6 months. Although the
      variance explained was small, it suggests better set-shifting capacity
      facilitates the improvement of insight at an early stage of the illness. 

PMID- 24560613
TI  - Text messaging: are dependency and Excessive Use discretely different for
      Japanese university students?
AB  - Text messaging may be excessive and young people may be dependent on it. We
      distributed the Self-perception of Text-message Dependency Scale (STDS), Hospital
      Anxiety and Depression Scale (HADS), Temperament and Character Inventory (TCI),
      and Relationship Questionnaire (RQ) to 223 Japanese university students in a two
      wave study, separated by a 5-month interval. The STDS yielded a three-factor
      structure. The STDS scores across the two measurement occasions were stable
      across time (except for the Relationship Maintenance subscale). A hierarchical
      cluster analysis suggested a three-class structure interpreted as Normal Users,
      Excessive Users, and Dependent Users. Excessive Users and Dependent Users were
      characterized by a young age at initial mobile phone use, more frequent use of
      text messaging, higher Novelty Seeking, and better Other-Model patterns of adult
      attachment. Unlike Excessive Users, Dependent Users were characterized by lower
      Self-directedness, poorer Self-Model of adult attachment, and higher anxiety and
      depression. The Excessive Users, but not the Dependent Users, were characterized
      by high Reward Dependence and Co-operativeness. The present study demonstrated
      that the STDS has a robust factor structure, good construct validity, and
      temporal stability (except for Relationship Maintenance subscale); students could
      be classified into normal, excessive, and Dependent Users of the text messaging;
      and Dependent Users were characterized by Excessive Use and personality
      immaturity. 

PMID- 24560614
TI  - Transcriptomic reprogramming of genus Paracoccidioides in dimorphism and host
      niches.
AB  - The thermodimorphic fungi Paracoccidioides brasiliensis and Paracoccidioides
      lutzii are the etiologic agents of Paracoccidioidomycosis (PCM), the most
      important endemic systemic mycosis in Latin America. Paracoccidioides grows as
      saprophytic mycelia that produce infective conidia propagules, which are inhaled
      into the lungs where the fungus converts to the pathogenic yeast form. From the
      lungs, Paracoccidioides may disseminate through blood and lymphatics to several
      other organs and tissues. During the last decade we have witnessed the generation
      of a large amount of transcriptomic data regarding the events leading to the
      morphological transition and host niche adaptation. In this review we summarize
      those findings and discuss the consequence of gene expression plasticity in the
      persistence and survival of this pathogen. In addition, we discuss the future
      trends on the host-pathogen studies and how new molecular strategies, such as RNA
      seq, dual RNA-seq and Chip-Seq can be powerful tools to improve our understanding
      on the pathobiology of this systemic mycosis in Latin America. 

PMID- 24560615
TI  - Ligninolytic peroxidase gene expression by Pleurotus ostreatus: differential
      regulation in lignocellulose medium and effect of temperature and pH.
AB  - Pleurotus ostreatus is an important edible mushroom and a model lignin degrading
      organism, whose genome contains nine genes of ligninolytic peroxidases,
      characteristic of white-rot fungi. These genes encode six manganese peroxidase
      (MnP) and three versatile peroxidase (VP) isoenzymes. Using liquid chromatography
      coupled to tandem mass spectrometry, secretion of four of these peroxidase
      isoenzymes (VP1, VP2, MnP2 and MnP6) was confirmed when P. ostreatus grows in a
      lignocellulose medium at 25 degrees C (three more isoenzymes were identified by
      only one unique peptide). Then, the effect of environmental parameters on the
      expression of the above nine genes was studied by reverse transcription
      quantitative PCR by changing the incubation temperature and medium pH of P.
      ostreatus cultures pre-grown under the above conditions (using specific primers
      and two reference genes for result normalization). The cultures maintained at 25
      degrees C (without pH adjustment) provided the highest levels of peroxidase
      transcripts and the highest total activity on Mn(2+) (a substrate of both MnP and
      VP) and Reactive Black 5 (a VP specific substrate). The global analysis of the
      expression patterns divides peroxidase genes into three main groups according to
      the level of expression at optimal conditions
      (vp1/mnp3>vp2/vp3/mnp1/mnp2/mnp6>mnp4/mnp5). Decreasing or increasing the
      incubation temperature (to 10 degrees C or 37 degrees C) and adjusting the
      culture pH to acidic or alkaline conditions (pH 3 and 8) generally led to
      downregulation of most of the peroxidase genes (and decrease of the enzymatic
      activity), as shown when the transcription levels were referred to those found in
      the cultures maintained at the initial conditions. Temperature modification
      produced less dramatic effects than pH modification, with most genes being
      downregulated during the whole 10 degrees C treatment, while many of them were
      alternatively upregulated (often 6h after the thermal shock) and downregulated
      (12h) at 37 degrees C. Interestingly, mnp4 and mnp5 were the only peroxidase
      genes upregulated under alkaline pH conditions. The differences in the
      transcription levels of the peroxidase genes when the culture temperature and pH
      parameters were changed suggest an adaptive expression according to environmental
      conditions. Finally, the intracellular proteome was analyzed, under the same
      conditions used in the secretomic analysis, and the protein product of the highly
      transcribed gene mnp3 was detected. Therefore, it was concluded that the absence
      of MnP3 from the secretome of the P. ostreatus lignocellulose cultures was
      related to impaired secretion. 

PMID- 24560618
TI  - Development of pectinate-ispagula mucilage mucoadhesive beads of metformin HCl by
      central composite design.
AB  - Ionotropically-gelled mucoadhesive beads of metformin HCl composed of low methoxy
      (LM) pectin-ispaghula husk mucilage (IHM) polymer-blend was developed and
      optimized using central composite design (spherical type, single center point,
      and alpha=1.414). Effects of LM pectin and IHM amounts on drug encapsulation
      efficiency (DEE) and cumulative drug release at 10h (R10h) were analysed using
      response surface methodology. The optimized beads containing metformin HCl (F-O)
      showed DEE of 86.98 +/- 3.26% and R10h of 47.20 +/- 1.28%. All these beads
      exhibited suitable controlled in vitro sustained drug release pattern with super
      case-II transport mechanism over 10h. These beads were also characterized by SEM
      and FTIR. The optimized beads also exhibited pH-dependent swelling, good
      mucoadhesivity with goat intestinal mucosa and significant hypoglycemic effect in
      alloxan-induced diabetic rats over prolonged period after oral administration,
      which could possibly be lucrative in terms of prolonged systemic absorption of
      metformin HCl maintaining tight blood glucose level and advanced patient
      compliance.

PMID- 24560617
TI  - Intranasal vaccination with recombinant receptor-binding domain of MERS-CoV spike
      protein induces much stronger local mucosal immune responses than subcutaneous
      immunization: Implication for designing novel mucosal MERS vaccines.
AB  - Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV) was originally
      identified in Saudi Arabia in 2012. It has caused MERS outbreaks with high
      mortality in the Middle East and Europe, raising a serious concern about its
      pandemic potential. Therefore, development of effective vaccines is crucial for
      preventing its further spread and future pandemic. Our previous study has shown
      that subcutaneous (s.c.) vaccination of a recombinant protein containing receptor
      binding domain (RBD) of MERS-CoV S fused with Fc of human IgG (RBD-Fc) induced
      strong systemic neutralizing antibody responses in vaccinated mice. Here, we
      compared local and systemic immune responses induced by RBD-Fc via intranasal
      (i.n.) and s.c. immunization pathways. We found that i.n. vaccination of MERS-CoV
      RBD-Fc induced systemic humoral immune responses comparable to those induced by
      s.c. vaccination, including neutralizing antibodies, but more robust systemic
      cellular immune responses and significantly higher local mucosal immune responses
      in mouse lungs. This study suggests the potential of developing MERS-CoV RBD
      protein into an effective and safe mucosal candidate vaccine for prevention of
      respiratory tract infections caused by MERS-CoV. 

PMID- 24560619
TI  - Physicochemical and release kinetics of natural and retrograded starch of Indian
      palmyrah shoots.
AB  - Starch was isolated from the shoots of Indian palmyrah (Borassus flabellifer L.)
      and it was subjected to the process of retrogradation. The influence of
      retrogradation on morphological, physicochemical and drug release properties was
      studied. Retrogradation of native starch changed its morphology from oval,
      elliptical to crystalline rods. Due to retrogradation there is an increase in
      amylose content and better hydration capacity, swelling and solubility power. The
      micromeritic properties of native and retrograded starch uncover its usage as
      excipients in tablet manufacturing. The retrograded starch showed better powder
      characteristics to that of native starch. The characteristic peaks for d
      glucopyranosyl ring confirms the carbohydrate nature of starch. The TGA data
      reveals that the retrograded starch shows less bound water to that of native
      starch during the first decomposition step. In-vitro release study reveals that
      the retrograded starch attained a better release retardant property and was best
      explained by Hixson-Crowell model. The result showed that retrograded starches
      can be used for the preparation of sustained release tablets. 

PMID- 24560622
TI  - Biodegradable poly(ester urethane) urea scaffolds for tissue engineering:
      Interaction with osteoblast-like MG-63 cells.
AB  - Porous three-dimensional scaffolds with potential for application as cancellous
      bone graft substitutes were prepared from aliphatic segmented poly(ester
      urethane) urea using the phase-inverse technique. Proton nuclear magnetic
      resonance, size-exclusion chromatography, electron spectroscopy for chemical
      analysis, secondary ion mass spectrometry, infrared spectroscopy, scanning
      electron microscopy, differential scanning calorimetry, computed tomography and
      mechanical tests were carried out, to characterize the scaffolds' physicochemical
      properties. Human osteosarcoma MG-63 cells were seeded into the scaffolds for 1,
      2, 3 and 4weeks to evaluate their potential to support attachment, growth and
      proliferation of osteogenic cells. The scaffold-cell interaction was assessed by
      analysis of DNA content, total protein amount, alkaline phosphatase activity and
      WST-1 assay. The scaffolds supported cell attachment, growth and proliferation
      over the whole culture period of 4weeks (DNA, total protein amount). There was,
      however, a reduction in the WST-1 assay values at 4weeks, which might suggest a
      reduction in the rate of cell proliferation at this time.

PMID- 24560621
TI  - Translation of an engineered nanofibrous disc-like angle-ply structure for
      intervertebral disc replacement in a small animal model.
AB  - Intervertebral disc degeneration has been implicated in the etiology of low back
      pain; however, the current surgical strategies for treating symptomatic disc
      disease are limited. A variety of materials have been developed to replace disc
      components, including the nucleus pulposus (NP), the annulus fibrosus (AF) and
      their combination into disc-like engineered constructs. We have previously shown
      that layers of electrospun poly(epsilon-caprolactone) scaffold, mimicking the
      hierarchical organization of the native AF, can achieve functional parity with
      native tissue. Likewise, we have combined these structures with cell-seeded
      hydrogels (as an NP replacement) to form disc-like angle-ply structures (DAPS).
      The objective of this study was to develop a model for the evaluation of DAPS in
      vivo. Through a series of studies, we developed a surgical approach to replace
      the rat caudal disc with an acellular DAPS and then stabilized the motion segment
      via external fixation. We then optimized cell infiltration into DAPS by including
      sacrificial poly(ethylene oxide) layers interspersed throughout the angle-ply
      structure. Our findings illustrate that DAPS are stable in the caudal spine, are
      infiltrated by cells from the peri-implant space and that infiltration is
      expedited by providing additional routes for cell migration. These findings
      establish a new in vivo platform in which to evaluate and optimize the design of
      functional disc replacements.

PMID- 24560620
TI  - NLRC3, a member of the NLR family of proteins, is a negative regulator of innate
      immune signaling induced by the DNA sensor STING.
AB  - Stimulator of interferon genes (STING, also named MITA, MYPS, or ERIS) is an
      intracellular DNA sensor that induces type I interferon through its interaction
      with TANK-binding kinase 1 (TBK1). Here we found that the nucleotide-binding,
      leucine-rich-repeat-containing protein, NLRC3, reduced STING-dependent innate
      immune activation in response to cytosolic DNA, cyclic di-GMP (c-di-GMP), and DNA
      viruses. NLRC3 associated with both STING and TBK1 and impeded STING-TBK1
      interaction and downstream type I interferon production. By using purified
      recombinant proteins, we found NLRC3 to interact directly with STING.
      Furthermore, NLRC3 prevented proper trafficking of STING to perinuclear and
      punctated region, known to be important for its activation. In animals, herpes
      simplex virus 1 (HSV-1)-infected Nlrc3(-/-) mice exhibited enhanced innate
      immunity and reduced morbidity and viral load. This demonstrates the intersection
      of two key pathways of innate immune regulation, NLR and STING, to fine tune host
      response to intracellular DNA, DNA virus, and c-di-GMP. 

PMID- 24560623
TI  - Production of bioactive hydroxyflavones by using monooxygenase from Saccharothrix
      espanaensis.
AB  - Biocatalysts are a valuable tool for the structural modification of fine
      chemicals. Flavonoids possess several biological activities, which are correlated
      to their antioxidant activity. The numbers of hydroxyl groups in flavonoids are
      critical for their antioxidant activity. Development of biocatalysts for
      hydroxylation of flavonoids is challenging because of the difficulty in
      expressing flavonoid hydroxylase in Escherichia coli. In this study, a
      monooxygenase from Saccharothrix espanaensis (Sam5) was used for regioselective
      hydroxylation of flavonoids. We found that Sam5 hydroxylated isoflavones,
      flavanones, and flavones but did not produce any detectable hydroxylated product
      with flavonols. In addition, coexpression of P450 reductase with Sam5 in E. coli
      enhanced hydroxylation by approximately from 34 to 50%, depending on the
      flavonoid used. The production of two bioactive flavonoids, 8-hydroxyluteolin and
      3'-hydroxydaidzein was optimized using this Sam5 system. Approximately 88mg/L of
      8-hydroxyluteolin and 75mg/L of 3'-hydroxydaidzein were obtained. These results
      indicate that the Sam5 system could be used for the production of bioactive
      hydroxylated flavonoids. 

PMID- 24560624
TI  - Recent AHA/ACC cholesterol guidelines: vice or virtue?

PMID- 24560625
TI  - Selective binding of naphthoquinone derivatives to serum albumin proteins and
      their effects on cytotoxicity.
AB  - Naphthoquinone derivatives such as lapachol, plumbagin, dichloroallyl lawsone
      show anticancer activity and generally cytotoxicity measurements are carried out
      in presence of bovine serum albumin; so understanding on the ability of serum
      albumin binding with such derivatives are essential. We have investigated
      cytotoxicity and serum albumin binding of a series of structurally related
      naphthoquinone derivatives. Substrate dependency and high selectivity in binding
      of naphthoquinone tethered carboxylic acids or pyridines with bovine serum
      albumin (BSA) and human serum albumin (HSA) are observed. For example, the
      binding constant of BSA with 3-(1,4-dihydro-2-methyl-1,4-dioxonaphthalen-3yl
      thio)propanoic acid is ~594 times higher than 3-(1,4-dioxo-1,4-dihydronaphthalen
      2-yl-amino)benzoic acid; whereas 4-(1,4-dioxo-1,4-dihydronaphthalen-2-yl
      amino)benzoic acid shows ~367 times higher binding constant than the latter
      compound. The BSA weakly bind to pyridine tethered naphthoquinones, whereas HSA
      does not binds with them. The binding constant of HSA with 2-(1,4-dihydro-2
      methyl-1,4-dioxonaphthalene-3-ylthio)benzoic acid is 134 times higher than the
      HSA binding constant with 2,2'-(1,4-dihydro-1,4-dioxo-naphthalen-2,3
      diylthio)dipropanoic acid. Among the naphthoquinone carboxylic acids, the 3-(1,4
      dioxo-1,4-dihydronaphthalen-2-yl-amino)benzoic acid binds selectively to BSA, but
      it does not bind to HSA. The 2-hydroxybenzoic acid or 4-mercaptobenzoic acid
      strongly binds to BSA. The binding of BSA with 4-hydroxybenzoic acid or 2
      mercaptobenzoic acid are insignificant. We have not observed clear relationships
      of structure of naphthoquinone derivatives versus serum albumin binding, but
      could identify the compound having the best IC50 values of cytotoxicity among the
      twelve naphthoquinone compounds. The compound 3-(1,2-dihydro-1,2-dioxonaphthalen
      4-yl-thio)propanoic acid in four cancer cell lines has IC50 values in the range
      2.7-7.6MUM. This compound also has optimum binding constant with BSA
      (35.042*10(3)Lmol(-1)) or HSA (21.427*10(3)Lmol(-1)). The cytotoxicity values of
      the compounds were influenced by concentration of BSA. 

PMID- 24560626
TI  - Editorial overview: Nucleic acid movers and shakers.

PMID- 24560627
TI  - Late-onset group B streptococcus disease in the late-preterm neonate.

PMID- 24560628
TI  - Optimizing linear growth measurement in children.
AB  - A child's pattern of linear growth is one of the most sensitive indicators of
      health and well-being. However, many health care personnel use casual techniques
      and faulty instruments to measure children's growth and keep imprecise growth
      charts, making interpretation of growth patterns problematic. This situation can
      delay diagnosis and treatment of children with growth disorders and other
      conditions that affect growth. It can also lead to undue anxiety and unnecessary
      evaluation of children who are actually growing well. A clinical practice
      guideline was developed to optimize the accuracy and reliability of linear growth
      measurement. This article presents strategies to implement the guideline and
      thereby increase awareness of the importance of standardized growth measurement
      techniques and instruments, facilitate staff training and competency, and
      encourage standardized record keeping. These strategies will give providers more
      confidence in their interpretation of children's growth patterns and allow them
      to recognize potential problems, possibly before other symptoms appear. 

PMID- 24560629
TI  - Quantitative EEG (QEEG) in psychiatry: diagnostic or prognostic use?

PMID- 24560630
TI  - Pattern analysis of nerve enlargement using ultrasonography in chronic
      inflammatory demyelinating polyneuropathy.
AB  - OBJECTIVE: Focal nerve enlargement is a characteristic finding in chronic
      inflammatory demyelinating polyneuropathy (CIDP). We performed this study to
      assess the distribution of nerve enlargement through ultrasonographic examination
      of peripheral nerves and to correlate the ultrasonographic findings with clinical
      features. METHODS: To compare the ultrasonographic features of 10 subjects with
      CIDP with those of 18 healthy controls, we bilaterally measured the cross
      sectional areas (CSA) of the vagus, brachial plexus, musculocutaneous, median,
      ulnar, radial, sciatic, tibial, common peroneal, and sural nerves. We also
      analyzed correlations between CSAs and various clinical and electrophysiological
      features. RESULTS: Mean CSAs were significantly larger in CIDP patients than
      controls, especially at proximal and non-entrapment sites. CSAs were
      significantly correlated with muscle strength at initial presentation, but not at
      the time of ultrasonography. The CSAs of the median and ulnar nerves at the mid
      forearm, tibial nerve at 7 cm proximal to the medial malleolus, and sural nerve
      correlated with the nerve conduction velocity of the corresponding region.
      CONCLUSION: Ultrasonography revealed widely distributed nerve enlargement,
      especially in proximal regions and non-entrapment sites, in patients with CIDP
      compared with healthy controls. Nerve enlargement correlated well with the
      electrophysiologic function of the nerve, but not current clinical status.
      SIGNIFICANCE: Pattern analysis of nerve enlargement using ultrasonography is a
      supportive tool in the diagnosis of CIDP.

PMID- 24560631
TI  - Selective sentinel lymph node biopsy after neoadjuvant chemotherapy in breast
      cancer: results of the GEICAM 2005-07 study.
AB  - INTRODUCTION: A controversial aspect of breast cancer management is the use of
      sentinel lymph node biopsy (SLNB) in patients requiring neoadjuvant chemotherapy
      (NCT). This paper discusses the detection rate (DT) and false negatives (FN) of
      SLNB after NCT to investigate the influence of initial nodal disease and the
      protocols applied. METHODS: Prospective observational multicenter study in women
      with breast cancer, treated with NCT and SLNB post-NCT with subsequent
      lymphadenectomy. DT and FN rates were calculated, both overall and depending on
      the initial nodal status or the use of diagnostic protocols pre-SLNB. RESULTS: No
      differences in DT between initial node-negative cases and positive cases were
      found (89.8 vs. 84.4%, P=.437). Significant differences were found (94.1 vs.
      56.5%, P=0,002) in the negative predictive value, which was lower when there was
      initial lymph node positivity, and a higher rate of FN, not significant (18.2 vs.
      43.5%, P=.252) in the same cases. The axillary study before SLNB and after the
      NCT, significantly decreased the rate of FN in patients with initial involvement
      (55.6 vs 12.5, P=0,009). CONCLUSIONS: NCT means less DT and a higher rate of FN
      in subsequent SLNB, especially if there is initial nodal involvement. The use of
      protocols in axillary evaluation after administering the NCT and before BSGC,
      decreases the FN rate in these patients.

PMID- 24560632
TI  - PEComa, a rare epithelioid cell tumor.

PMID- 24560633
TI  - From Bariatric Surgery to a Radical Total Gastrectomy: a Change in the Proposed
      Surgical Procedure Due to Intraoperative Diagnosis of Carcinoid Tumour.

PMID- 24560634
TI  - Self-described nursing roles experienced during care of dying patients and their
      families: a phenomenological study.
AB  - BACKGROUND: Critical care nurses frequently care for dying patients and their
      families. Little is known about the roles experienced and perceived by bedside
      nurses as they care for dying patients and their families. OBJECTIVES: The
      purpose of this study was to understand the experiences of critical care nurses
      and to understand their perceptions of activities and roles that they performed
      while caring for patients and families during the transition from aggressive life
      saving care to palliative and end-of-life care. METHODS: A descriptive,
      phenomenological study was conducted and a purposive sampling strategy was used
      to recruit 19 critical care nurses with experience caring for dying patients and
      their families. Individual interviews were conducted and audio-recorded.
      Coliazzi's method of data analysis was utilised to inductively determine themes,
      clusters and categories. Data saturation was achieved and methodological rigour
      was established. RESULTS: Categories that evolved from the data included
      educating the family, advocating for the patient, encouraging and supporting
      family presence, managing symptoms, protecting families and creating positive
      memories and family support. Participants also identified the importance of
      teaching and mentoring novice clinicians. CONCLUSIONS: The results of this study
      have important implications for clinical practice, education and research for
      optimal preparation in providing end-of-life care.

PMID- 24560635
TI  - Bench to bedside development of GMP grade Rhenium-188-HEDP, a radiopharmaceutical
      for targeted treatment of painful bone metastases.
AB  - Bone-targeting therapeutic radiopharmaceuticals are effective agents for
      treatment of painful bone metastases. Rhenium-188-HEDP is such a therapeutic
      radiopharmaceutical and has advantages over commercially available alternatives
      in terms of efficacy, safety and the ability to be produced on-site, allowing
      rapid treatment upon presentation of patients with pain. Unlike many other
      radiopharmaceuticals, there are no standardized preparation methods for Rhenium
      188-HEDP. It is known, however, that drug composition may not only affect
      stability of the final drug product, but it may also influence bone affinity and,
      thus, efficacy. Furthermore, for support of clinical studies with Rhenium-188
      HEDP as an investigational medicinal product, preparation of this
      radiopharmaceutical has to be performed under GMP conditions. To our knowledge,
      no group has reported on the preparation of Rhenium-188-HEDP under GMP conditions
      or on stock production of sterile non-radioactive starting materials. We present
      the production of GMP grade Rhenium-188-HEDP for application of this therapeutic
      radiopharmaceutical in routine clinical practice and for support of clinical
      studies. In addition, bio-distribution data of Rhenium-188-HEDP in mice and in
      patients with bone metastases originating from prostate cancer are presented. 

PMID- 24560636
TI  - In vitro duodenal lipolysis of lipid-based drug delivery systems studied by HPLC
      UV and HPLC-MS.
AB  - Oral drug delivery systems based on lipids are biodegraded in a process called
      lipolysis to release free fatty acids and monoglycerides. The rate of this
      lipolysis is usually measured by pH titration. Nevertheless, this technique has
      some limitations, such as not providing any information about the actual
      composition of the lipolytic products. In this study, we propose a method to
      analyze these products during and after lipolysis using HPLC. For the first time,
      HPLC-UV and HPLC-MS have been used to investigate in vitro duodenal lipolysis of
      long- and medium-chain triglycerides nanoemulsions. These results have been
      compared with pH titration, revealing the complementarity of both techniques. The
      main free fatty acids and monoglycerides produced were effectively identified and
      quantified as they were formed and after the lipolysis experiment and subsequent
      ultracentrifugation. The release of fatty acids during lipolysis was
      qualitatively similar between the compared techniques, although a partial
      precipitation of medium chain fatty acids could be revealed with HPLC-MS. In
      addition, the release of two hydrophobic compounds with health benefits,
      oleoylethanolamide and carnosic acid, was investigated. In conclusion, this study
      may serve as a starting point for subsequent investigations regarding
      biodegradation and absorption of lipid-based drug delivery systems using HPLC. 

PMID- 24560637
TI  - Simultaneous quantification of drug release and erosion from hypromellose
      hydrophilic matrices.
AB  - Hypromellose, HPMC, is frequently used to control drug release from matrix tablet
      formulations. Drug is released by a combination of diffusion through and erosion
      of, the matrix and is usually measured invitro by separate dissolution and
      swelling/erosion studies. The present study was designed to measure matrix
      erosion, polymer dissolution and drug release kinetics and their inter
      relationship in a single experiment using a phenol-sulphuric acid assay to
      quantify dissolved HPMC alongside spectrophotometrical analysis of drug release.
      HPMC-based matrix tablets were manufactured containing two drugs at various
      drug:HPMC ratios. Drug release was determined and the degree of erosion was
      calculated by gravimetry. Results showed the matrix erosion rate and drug release
      were dependent on HPMC content and drug solubility, as expected. It was also
      apparent that the erosion rate was directly related to the drug release kinetics
      and comparative analysis of both matrix erosion techniques showed a high level of
      correlation. The findings show that a simple and inexpensive assay can be
      utilised not only to quantify HPMC but can also be used to calculate the degree
      of erosion of tablet matrices, negating the need for a separate study and
      providing a simplified practical approach that may be of use during product
      optimization. 

PMID- 24560638
TI  - The physicochemical interactive mechanism between nanoparticles and raffinose
      during freeze-drying.
AB  - New methods of preparing nanoparticles and in vivo studies of their behavior have
      been the subject of much study. However, there exist few studies on maintaining
      the nanoparticle size. In this work, we report on the interaction mechanism
      between raffinose and nanoparticles during freeze-drying. The mean particle size
      of the rehydrated freeze-dried raffinose-containing nanoparticles (170.5 nm) was
      similar to the initial particle size before freeze-drying (156.1 nm), indicating
      that the particle size was maintained. The powder X-ray diffraction of the freeze
      dried raffinose-containing nanoparticles shows a halo pattern, while that of the
      normal-dried raffinose shows a crystalline pattern. No endothermic peak of the
      freeze-dried raffinose appeared, while the normal-dried raffinose had an
      endothermic peak at 84.0  degrees C. These results suggest that there exists a
      relationship between the nanoparticles and the raffinose, and that the
      relationship depends on whether the mixture is freeze-dried or normal-dried. In
      the case of normal drying, the raffinose molecules have space and time to arrange
      themselves into regular arrangement because the nanoparticles and raffinose
      molecules can move around freely in water. In contrast, in the case of freeze
      drying, the moisture was sublimed while the raffinose molecules and nanoparticles
      were immobilized in the ice, thereby preventing aggregation.

PMID- 24560639
TI  - Vitamin E nanoemulsions characterization and analysis.
AB  - The aims of this work were to characterize vitamin E/canola oil nanoemulsions and
      to develop a practical RP-HPLC method for vitamin E acetate estimation in the
      canola oil nanoemulsions. Currently available methods to analyze vitamin E in
      lipid-emulsions are time-consuming and do not allow adequate separation of
      vitamin E and its esters. The nanoemulsions were characterized for partition
      coefficient between emulsion phases, drug loading, free drug, micellar
      solubilization, encapsulation efficiency and vitamin E concentration in the
      emulsion external aqueous phase as a function of time. Formulation stability
      under stress conditions was also evaluated. The nanoemulsions were stable during
      the test period at 25 and 32  degrees C with no significant change in mean
      droplet diameter. The results suggest that prolonged release of lipophilic drugs
      can be achieved using nanoemulsions. The RP-HPLC method developed showed
      linearity, selectivity and efficiency. To the best of our knowledge, this is the
      first practical method for vitamin E analysis in lipid-emulsions. This method may
      also be applied to the analysis of vitamin E and its esters in other lipid
      formulations, and for quality control purposes.

PMID- 24560640
TI  - Interlaboratory testing of Insent e-tongues.
AB  - The first interlaboratory testing of electronic taste sensing systems was
      performed within five participating centers, each working with the Insent (Insent
      Inc., Atsugi-Shi, Japan) e-tongue. Preparation of the samples for the comprised
      four experiments, shipping of the samples and evaluation of the results was
      performed at the University of Duesseldorf. The sensitivity (in this case the
      difference between lowest and highest sensor response) and slope of the
      regression line values, obtained within Experiment 1 and 2, have been found to
      serve as applicable evaluation criterions for interlaboratory comparability.
      Modified sensor responses could be attributed to aged sensors, but did not
      influence the results of either Experiment 3, dealing with the evaluation of film
      formulations, or Experiment 4, dealing with the evaluation of minitablet
      formulations, in a great amount. Presented PCA Score and Loading Scatter Plots as
      well as Euclidean distance patterns based on the raw sensor responses confirmed
      the comparable performance of Insent e-tongues of the participating centers. 

PMID- 24560641
TI  - Clay as a matrix former for spray drying of drug nanosuspensions.
AB  - Utilization of sugars (e.g. lactose, sucrose) as matrix formers for spray drying
      of drug nanosuspensions is associated with two drawbacks: (1) sugars are
      incapable of preventing agglomeration of drug nanoparticles (NPs) in the
      suspension state; and (2) the spray-dried sugars are usually amorphous and
      hygroscopic. This work aimed to apply a clay, montmorillonite (MMT) as an
      alternative matrix former for spray drying of drug nanosuspensions with
      fenofibrate (feno) as a model compound. Drug nanosuspensions were synthesized by
      liquid antisolvent precipitation with different amount of MMT followed by spray
      drying. It is found that MMT is able to reduce the agglomeration of drug
      nanoparticles in the suspension state, as observed from the gradual alleviation
      of the clogging with the increased clay during the spray drying. The spray-dried
      feno NPs/MMT powders exhibited a much lower moisture sorption than spray-dried
      feno NPs/lactose powders as evidenced by the dynamic vapor sorption (DVS)
      analysis. The dissolution within 5 min for the spray-dried feno NPs/MMT powders
      at drug:MMT weight ratio of 1:3 was 81.4 +/- 1.8% and the total dissolution
      within 60 min was 93.4 +/- 0.9%. Our results demonstrate that MMT is a useful
      matrix former for preservation of the high dissolution rate of nanosized drug
      particles after drying.

PMID- 24560642
TI  - Surface layer proteins isolated from Clostridium difficile induce clearance
      responses in macrophages.
AB  - Clostridium difficile is the leading cause of hospital-acquired diarrhoea
      worldwide, and if the bacterium is not cleared effectively it can pose a risk of
      recurrent infections and complications such as colitis, sepsis and death. In this
      study we demonstrate that surface layer proteins from the one of the most
      frequently acquired strains of C. difficile, activate mechanisms in murine
      macrophage in vitro that are associated with clearance of bacterial infection.
      Surface layer proteins (SLPs) isolated from C. difficile induced the production
      of pro-inflammatory cytokines and chemokines and increased macrophage migration
      and phagocytotic activity in vitro. Furthermore, we also observed up-regulation
      of a number of cell surface markers on the macrophage, which are important in
      pathogen recognition and antigen presentation. The effects of SLPs on macrophages
      were reversed in the presence of a p38 inhibitor, indicating the potential
      importance of this signalling protein in how SLP activates the immune system. In
      conclusion this study shows that surface layer proteins from a common strain of
      C. difficile can activate a clearance response in macrophage and suggests that
      these proteins are important in clearance of C. difficile infection.
      Understanding how the immune system clears C. difficile infection could offer
      important insights for new treatment strategies.

PMID- 24560643
TI  - Posterior skeletal development and the segmentation clock period are sensitive to
      Lfng dosage during somitogenesis.
AB  - The segmental structure of the axial skeleton is formed during somitogenesis.
      During this process, paired somites bud from the presomitic mesoderm (PSM), in a
      process regulated by a genetic clock called the segmentation clock. The Notch
      pathway and the Notch modulator Lunatic fringe (Lfng) play multiple roles during
      segmentation. Lfng oscillates in the posterior PSM as part of the segmentation
      clock, but is stably expressed in the anterior PSM during presomite patterning.
      We previously found that mice lacking overt oscillatory Lfng expression in the
      posterior PSM (Lfng(?FCE)) exhibit abnormal anterior development but relatively
      normal posterior development. This suggests distinct requirements for
      segmentation clock activity during the formation of the anterior skeleton
      (primary body formation), compared to the posterior skeleton and tail (secondary
      body formation). To build on these findings, we created an allelic series that
      progressively lowers Lfng levels in the PSM. Interestingly, we find that further
      reduction of Lfng expression levels in the PSM does not increase disruption of
      anterior development. However tail development is increasingly compromised as
      Lfng levels are reduced, suggesting that primary body formation is more sensitive
      to Lfng dosage than is secondary body formation. Further, we find that while low
      levels of oscillatory Lfng in the posterior PSM are sufficient to support
      relatively normal posterior development, the period of the segmentation clock is
      increased when the amplitude of Lfng oscillations is low. These data support the
      hypothesis that there are differential requirements for oscillatory Lfng during
      primary and secondary body formation and that posterior development is less
      sensitive to overall Lfng levels. Further, they suggest that modulation of the
      Notch signaling by Lfng affects the clock period during development. 

PMID- 24560644
TI  - Cleavage of the Drosophila screw prodomain is critical for a dynamic BMP
      morphogen gradient in embryogenesis.
AB  - Dorsoventral patterning of the Drosophila embryo is regulated by graded
      distribution of bone morphogenetic proteins (BMPs) composed of two ligands,
      decapentaplegic (Dpp) a BMP2/4 ortholog and screw (Scw) a BMP5/6/7/8 family
      member. scw(E1) encodes an unusual allele that was isolated as a dominant
      enhancer of partial loss-of-function mutations in dpp. However, the molecular
      mechanisms that underlie this genetic interaction remain to be addressed. Here we
      show that scw(E1) contains a mutation at the furin cleavage site within the
      prodomain that is crucial for ligand production. Furthermore, our data show that
      Scw(E1) preferentially forms heterodimers with Dpp rather than homotypic dimers,
      providing a possible explanation for the dominant negative phenotype of scw(E1)
      alleles. The unprocessed prodomain of Scw(E1) remains in a complex with the
      Dpp:Scw heterodimer, and thus could interfere with interaction of the ligand with
      the extracellular matrix, or the kinetics of processing/secretion of the ligand
      in vivo. These data reveal novel mechanisms by which post-translational
      regulation of Scw can modulate Dpp signaling activity. 

PMID- 24560645
TI  - A respiratory product for children--development and submission experiences.
AB  - The article highlights experiences for the development and submission of an
      inhalation product for children. 

PMID- 24560646
TI  - Preparation and characterization of spray-dried powders intended for pulmonary
      delivery of insulin with regard to the selection of excipients.
AB  - The aim of this study was to produce microparticles with optimal aerodynamic
      diameter for deep lung delivery (i.e., 1-3MUm) of a protein drug intended for
      systemic absorption, using a combination of generally regarded as safe (GRAS)
      excipients. Based on the preliminary experiments, mannitol, l-alanine, sodium
      alginate, chitosan and dipalmitoylphosphatidilcholine (DPPC) were chosen as
      excipients and human insulin as a model protein drug. Dry powders were prepared
      by spray-drying. Powders with varying yields (29-80%) and low tapped densities
      (0.22-0.38 g/cm(3)) were obtained. Scanning electron microscopy (SEM) revealed
      distinctive particle morphologies among formulations from isolated spherical to
      highly folded particles. Aerodynamic properties were assessed by next generation
      impactor (NGI). Mass median aerodynamic diameter (MMAD) and fine particle
      fraction (FPF) ranged from 2.1 to 4.6 MUm and 46 to 81%, respectively. A
      comparative study of protein release from microparticles was conducted in vitro
      using an open membrane system with more than 50% cumulative release in all
      formulations which followed different kinetic models. Insulin's integrity was
      investigated by spectrofluorimetry and electrophoresis, and no tangible changes
      were observed in the structure of insulin. Of the formulations studied, the
      third, containing mannitol/sodium alginate/insulin/sodium citrate showed
      promising characteristics, optimal for systemic delivery of proteins via deep
      lung deposition.

PMID- 24560647
TI  - Influence of particle geometry and PEGylation on phagocytosis of particulate
      carriers.
AB  - Particle geometry of micro- and nanoparticles has been identified as an important
      design parameter to influence the interaction with cells such as macrophages. A
      head to head comparison of elongated, non-spherical and spherical micro- and
      nanoparticles with and without PEGylation was carried out to benchmark two
      phagocytosis inhibiting techniques. J774.A1 macrophages were incubated with
      fluorescently labeled PLGA micro- and nanoparticles and analyzed by confocal
      laser scanning microscope (CLSM) and flow cytometry (FACS). Particle uptake into
      macrophages was significantly reduced upon PEGylation or elongated particle
      geometry. A combination of both, an elongated shape and PEGylation, had the
      strongest phagocytosis inhibiting effect for nanoparticles. 

PMID- 24560648
TI  - Differences in mortality, risk factors, and complications after open and
      endovascular repair of ruptured abdominal aortic aneurysms.
AB  - OBJECTIVE/BACKGROUND: Endovascular aneurysm repair (EVAR) for ruptured abdominal
      aortic aneurysm (rAAA) has faced resistance owing to the marginal evidence of
      benefit over open surgical repair (OSR). This study aims to determine the impact
      of treatment modality on early mortality after rAAA, and to assess differences in
      postoperative complications and long-term survival. METHODS: Patients treated
      between January 2000 and June 2013 were identified. The primary endpoint was
      early mortality. Secondary endpoints were postoperative complications and long
      term survival. Independent risk factors for early mortality were calculated using
      multivariate logistic regression. Survival estimates were obtained by means of
      Kaplan-Meier curves. RESULTS: Two hundred and twenty-one patients were treated
      (age 72 +/- 8 years, 90% male), 83 (38%) by EVAR and 138 (62%) by OSR. There were
      no differences between groups at the time of admission. Early mortality was
      significantly lower for EVAR compared with OSR (odds ratio [OR]: 0.45, 95%
      confidence interval [CI]: 0.21-0.97). Similarly, EVAR was associated with a
      threefold risk reduction in major complications (OR: 0.33, 95%CI: 0.15-0.71).
      Hemoglobin level <11 mg/dL was predictive of early death for patients in both
      groups. Age greater than 75 years and the presence of shock were significant risk
      factors for early death after OSR, but not after EVAR. The early survival benefit
      of EVAR over OSR persisted for up to 3 years. CONCLUSION: This study shows an
      early mortality benefit after EVAR, which persists over the mid-term. It also
      suggests different prognostic significance for preoperative variables according
      to the type of repair. Age and the presence of shock were risk factors for early
      death after OSR, while hemoglobin level on admission was a risk factor for both
      groups. This information may contribute to repair-specific risk prediction and
      improved patient selection.

PMID- 24560649
TI  - Strategy and long-term outcomes of endovascular treatment for Budd-Chiari
      syndrome complicated by inferior vena caval thrombosis.
AB  - OBJECTIVES: The aim of this study was to evaluate the strategy and long-term
      outcomes of endovascular treatment of Budd-Chiari syndrome (BCS) complicated by
      inferior vena cava (IVC) thrombosis. METHODS: The treatment strategy and outcomes
      of BCS complicated by IVC thrombosis were retrospectively evaluated in a single
      center study. The treatment was aimed at the IVC thrombus, not hepatic vein
      occlusion. All 133 patients with BCS complicated by IVC thrombosis from February
      2003 to March 2013 underwent endovascular treatment. For the fresh thrombus group
      (n=75) recanalization was performed after transcatheter thrombolysis with
      urokinase. For the mixed thrombus group (n=19) a small balloon pre-dilation of
      the IVC was performed first, followed by transcatheter thrombolysis using
      urokinase and a large balloon dilation of the IVC. For the old thrombus group
      (n=39) a large balloon dilation or/and stent placement was performed directly.
      Pre- and post-treatment follow-ups were recorded. RESULTS: The endovascular
      treatment was successful in 131 out of 133 patients (98.5%). Thirty seven
      patients had synchronous hepatic vein occlusion. The incidence of serious
      complications was 4.5% (6/133). Symptomatic pulmonary embolism occurred in three
      cases, cerebral hemorrhage in two, and cardiac tamponade in one. The cumulative 1
      , 5-, and 10-year primary patency rate was 96.3%, 84.0%, and 64.6%, respectively.
      The cumulative 1-, 5-, and 10-year secondary patency rate was 99.0%, 96.1% and
      91.3%, respectively. Segmental occlusion of the IVC and duration of anticoagulant
      therapy less than 6 months were independent risk factors for reocclusion.
      CONCLUSIONS: For patients with BCS complicated by IVC thrombosis, an
      individualized treatment strategy based on the property of the thrombus can
      result in excellent long-term patency.

PMID- 24560650
TI  - Primary vaccination with the LiESP/QA-21 vaccine (CaniLeish) produces a cell
      mediated immune response which is still present 1 year later.
AB  - Canine leishmaniasis, an important zoonotic disease of dogs, is the result of an
      ineffective and inappropriate immune response to infection with Leishmania
      infantum. It is widely accepted that the appropriate immune response is
      characterised by a T-helper (Th)1-dominated profile in an overall mixed Th1/Th2
      response. The absence of a strong Th1 response is associated with progression to
      the clinical disease. Thus, there is a need for an effective vaccine that could
      modulate the immune response to a more appropriate profile against the parasite.
      In this study we measured the impact of the LiESP/QA-21 canine vaccine, recently
      launched commercially in Europe, on selected humoral and cellular immune markers
      for one year after a primary vaccination course. The humoral response to
      vaccination was characterised by a predominantly IgG2 profile. Vaccinated dogs
      developed long-lasting cell-mediated immune responses against L. infantum,
      specifically with a stronger ability of macrophages to reduce intracellular
      parasite burdens in co-culture with autologous lymphocytes compared to control
      dogs (p=0.0002), which was correlated with induction of inducible nitric oxide
      synthase (iNOS) and production of nitric oxide (NO) derivatives. These results
      confirm that vaccination with LiESP/QA-21 is capable of inducing an appropriate
      Th1-dominated immune profile which persists for a full year. 

PMID- 24560651
TI  - Prognostic relevance of cancer-associated fibroblasts in human cancer.
AB  - Prognostication is an integral part of cancer diagnostic and helps oncologists to
      guide treatment decisions and therapy intensity. Accumulating evidence suggest
      that the stroma compartment also contains independent prognostic information,
      best exemplified by the impact of immune cells and cells of the vasculature on
      cancer progression. Similarly, strong experimental evidence exist that stromal
      fibroblasts, often designated cancer associated fibroblasts (CAFs), are actively
      involved in tumorigenesis. Thus, it can be anticipated that the molecular
      repertoire of CAFs is likewise important for the clinical behavior of the tumor.
      In this review we present recent studies addressing the prognostic impact of
      CAFs, with the focus on human lung and breast cancer. Several single markers have
      been suggested, either CAF specific or CAF derived, that in immunohistochemical
      studies have demonstrated independent association with survival. This includes
      members of the platelet derived growth factor receptor (PDGFR) family, CAF
      markers like podoplanin and fibroblast activation protein (FAP) as well as
      transcription factors (FoxF1) and secreted factors (matrix metalloproteinases
      (MMPs), SPARC). However, most studies are based on explorative evaluations on
      single patient cohorts and require further validation. Using a more comprehensive
      approach, microarray studies have been employed to create gene expression
      signatures that detect an activated fibroblast state. These "stroma signatures"
      have been applied to identify specific CAF features associated with prognosis in
      several independent data sets of breast and lung cancer patients. Early studies
      in breast cancer have also demonstrated that fibroblast features influence
      therapy response. Thus, many strategies have been used to present encouraging
      proof-of-concept findings that CAFs could be exploited for prognostication.
      However, these studies also highlight the difficulties to conclusively define an
      "activated stroma" and to identify the individual factors involved in clinically
      relevant tumor-stroma interactions. 

PMID- 24560652
TI  - Epithelial stem cells and intestinal cancer.
AB  - The mammalian intestine is comprised of an epithelial layer that serves multiple
      functions in order to maintain digestive activity as well as intestinal
      homeostasis. This epithelial layer contains highly proliferative stem cells which
      facilitate its characteristic rapid regeneration. How these stem cells contribute
      to tissue repair and normal homeostasis are actively studied, and while we have a
      greater understanding of the molecular mechanisms and cellular locations that
      underlie stem cell regulation in this tissue, much still remains undiscovered.
      This review describes epithelial stem cells in both intestinal and non-intestinal
      tissues, as well as the strategies that have been used to further characterize
      the cells. Through a discussion of the current understanding of intestinal self
      renewal and tissue regeneration in response to injury, we focus on how
      dysregulation of critical signaling pathways results in potentially oncogenic
      aberrations, and highlight issues that should be addressed in order for effective
      intestinal cancer therapies to be devised. 

PMID- 24560653
TI  - Expression of nitric oxide synthase (NOS) genes in channel catfish is highly
      regulated and time dependent after bacterial challenges.
AB  - Nitric oxide is well known for its roles in immune responses. As such, its
      synthesizing enzymes have been extensively studied from various species including
      some teleost fish species. However, the NOS genes have not been characterized in
      channel catfish (Ictalurus punctatus). In this study, we identified and
      characterized three NOS genes including one NOS1 and two NOS2 genes in channel
      catfish. Comparing with the NOS genes from other fish species, the catfish NOS
      genes are highly conserved in their structural features. Phylogenetic and
      syntenic analyses allowed determination of NOS1 and NOS2 genes of channel catfish
      and their orthology relationships. Syntenic analysis, as well as the phylogenetic
      analysis, indicated that the two NOS2 genes of catfish were lineage-specific
      duplication. The NOS genes were broadly expressed in most tested tissues, with
      NOS1 being expressed at the highest levels in the brain, NOS2b1 highly expressed
      in the skin and gill, and NOS2b2 lowly expressed in most of the tested tissues.
      The most striking findings of this study was that the expression of the NOS genes
      are highly regulated after bacterial infection, with time-dependent expression
      patterns that parallel the migration of macrophages. After Edwardsiella ictaluri
      challenge, dramatically different responses among the three NOS genes were
      observed. NOS1 was only significantly in the skin early after infection, while
      NOS2b1 was rapidly upregulated in gill, but more up-regulated in trunk kidney
      with the progression of the disease, suggesting such differences in gene
      expression may be reflective of the migration of macrophages among various
      tissues of the infected fish. In contrast to NOS1 and NOS2b1, NOS2b2 was normally
      expressed at very low levels, but it is induced in the brain and liver while
      significantly down-regulated in most other tissues. 

PMID- 24560655
TI  - Barriers to quality health care for the transgender population.
AB  - The transgender community is arguably the most marginalized and underserved
      population in medicine. A special issue focusing on men's health would be
      incomplete without mention of this vulnerable population, which includes those
      transitioning to and from the male gender. Transgender patients face many
      barriers in their access to healthcare including historical stigmatization, both
      structural and financial barriers, and even a lack of healthcare provider
      experience in treating this unique population. Historical stigmatization fosters
      a reluctance to disclose gender identity, which can have dire consequences for
      long-term outcomes due to a lack of appropriate medical history including
      transition-related care. Even if a patient is willing to disclose their gender
      identity and transition history, structural barriers in current healthcare
      settings lack the mechanisms necessary to collect and track this information.
      Moreover, healthcare providers acknowledge that information is lacking regarding
      the unique needs and long-term outcomes for transgender patients, which
      contributes to the inability to provide appropriate care. All of these barriers
      must be recognized and addressed in order to elevate the quality of healthcare
      delivered to the transgender community to a level commensurate with the general
      population. Overcoming these barriers will require redefinition of our current
      system such that the care a patient receives is not exclusively linked to their
      sex but also considers gender identity. 

PMID- 24560654
TI  - Characterization of swine leukocyte antigen (SLA) polymorphism by sequence-based
      and PCR-SSP methods in Chinese Bama miniature pigs.
AB  - The highly polymorphic swine leukocyte antigen (SLA) genes have been repeatedly
      shown to influence swine immune traits, disease resistance, vaccine
      responsiveness and tumour penetrance. Analysis of the SLA diversity in as many
      pig breeds as possible is important to clarify the relationships between SLA
      genes and diseases or traits, and develop these pigs as valuable animal models
      for biomedical research. The Chinese Bama miniature pig breed is an economically
      significant breed that is available at several research institutions in China. In
      this study, we identified a total of 32 alleles at five polymorphic SLA loci (SLA
      1, SLA-3, SLA-2, DRB1 and DQB1) representing nine class I and seven class II
      haplotypes using the reverse transcription polymerase chain reaction (RT-PCR)
      sequence-based typing (SBT) method. The possible functional sites of the SLA
      genes were predicted and analyzed by comparison with those of the human and
      mouse. Based on the sequence information, we subsequently developed a rapid PCR
      based typing assay using sequence-specific primers (PCR-SSP) to efficiently
      follow the SLA types of the progeny. In the studied cohort (2n = 562), the most
      prevalent Haplotype Hp-35.6 (SLA-1(*)1201, SLA-1(*)1301-SLA-3(*)0502-SLA-2(*)1001
      DRB1(*)0501-DQB1(*)0801) was identified in 182 Bama pigs with a frequency of
      32.38%. The presence of the duplicated SLA-1 locus was confirmed in five of the
      class I haplotypes. Moreover, we identified two crossovers within the class I
      region and one between the class I and class II regions, which corresponded to
      recombination frequencies of 0.36% and 0.18%, respectively. The information of
      this study is essential for an understanding of the SLA allelic architecture and
      diversity, and it will be helpful for studying the adaptive immune response and
      further developing the more effective vaccines in the context of SLA
      specificities.

PMID- 24560656
TI  - Comparison of anti-CCP autoantibodies measurement by ELISA and a bead-based assay
      in a large patient cohort.
AB  - OBJECTIVES: The aims of our study were to compare in a cohort of 705 patients the
      diagnostic performance of two tests to detect autoantibodies to cyclic
      citrullinated peptides (CCP) and to determine whether a bead-based assay within a
      multiplex flow immunoassay (MFA) can be used instead of an enzyme linked
      immunosorbent assay (ELISA) technique in routine practice. DESIGN AND METHODS:
      Six hundred and thirty patients with rheumatic symptoms and 75 patients with
      systemic lupus erythematosus (SLE) were tested for anti-CCP autoantibodies using
      two techniques: ELISA (Inova) and MFA (BioPlex, Bio-Rad). RESULTS: Using kappa
      coefficient, there was an excellent agreement between ELISA and MFA when
      comparing 630 patients with rheumatic symptoms (kappa coefficient, 0.82). In this
      cohort 174 patients were identified as suffering from RA, while 456 patients
      suffered from other diseases. Sensitivity and specificity values of anti-CCP
      autoantibodies for RA were 70.7% and 92.3% for ELISA and 64.4% and 92.8% for MFA.
      The positive and negative predictive values were 77.4% and 89.2% for ELISA and
      77.2% and 87.2% for MFA, respectively. There were no differences in the
      diagnostic performances between the two assays (Z=0.67). The specificity values
      of anti-CCP autoantibodies analysing patients with SLE were 97.3% with MFA and
      96% with ELISA with an excellent agreement between the methods (98.7%; kappa
      coefficient, 0.79). CONCLUSION: Concordance between ELISA and MFA is high in
      routine practice. Overall, MFA is a powerful tool for rapid assessment of anti
      CCP autoantibodies and can replace the ELISA technique, which could be used as a
      second-line test in some cases.

PMID- 24560658
TI  - Reply to "Response to locoregional treatment and alpha-fetoprotein trend in liver
      transplant candidates for HCC: dwarfs standing on the shoulders of giants".

PMID- 24560659
TI  - Influence of CD8 T cell priming in liver and gut on the enterohepatic
      circulation.
AB  - BACKGROUND & AIMS: The enterohepatic circuit of T cells may be responsible for
      the development of autoimmune liver disease. We employed transgenic mice to
      characterize phenotype and migration patterns of CD8 T cells activated in liver
      and gut. METHODS: We studied the migration of antigen-specific CD8 T cells primed
      in liver or gut after transfer in wild-type mice or mice that express ovalbumin
      in liver or gut. We performed transcriptome analysis of these two distinct T cell
      populations and confirmed our findings by flow cytometry. RESULTS: Specific
      migration patterns were induced by activation of CD8 T cells in gut or liver. Gut
      activated CD8 T cells expressed alpha4beta7 and CCR9 and migrated to the gut and
      to the liver. Liver-activated T cells expressed integrins alpha4, alpha6, beta1,
      alpha4beta7 as well as CD62L, Ly6C, and neuropilin-1 and retained the capability
      to re-circulate through lymph nodes. Presence of the antigen increased retention
      of both types of activated T cells in the liver, but migration of liver-activated
      T cells to the gut was prohibited. CONCLUSIONS: CD8 T cells primed in the liver
      in vivo are not capable of migrating to the gut, implying that the enterohepatic
      circuit of CD8 T cells is in fact a one-way road from the gut to the liver.
      Priming of CD8 T cells in the liver results in a distinct phenotype with
      attributes of central memory cells and induces a unique homing pattern. Gut
      primed T cells preferentially home to the liver, in principle enabling them to
      induce autoimmune liver disease.

PMID- 24560657
TI  - Characterization of animal models for primary sclerosing cholangitis (PSC).
AB  - Primary sclerosing cholangitis (PSC) is a chronic cholangiopathy characterized by
      biliary fibrosis, development of cholestasis and end stage liver disease, high
      risk of malignancy, and frequent need for liver transplantation. The poor
      understanding of its pathogenesis is also reflected in the lack of effective
      medical treatment. Well-characterized animal models are utterly needed to develop
      novel pathogenetic concepts and study new treatment strategies. Currently there
      is no consensus on how to evaluate and characterize potential PSC models, which
      makes direct comparison of experimental results and effective exchange of study
      material between research groups difficult. The International Primary Sclerosing
      Cholangitis Study Group (IPSCSG) has therefore summarized these key issues in a
      position paper proposing standard requirements for the study of animal models of
      PSC. 

PMID- 24560660
TI  - Nod2 deficiency protects mice from cholestatic liver disease by increasing renal
      excretion of bile acids.
AB  - BACKGROUND & AIMS: Chronic liver disease is characterized by fibrosis that may
      progress to cirrhosis. Nucleotide oligomerization domain 2 (Nod2), a member of
      the Nod-like receptor (NLR) family of intracellular immune receptors, plays an
      important role in the defense against bacterial infection through binding to the
      ligand muramyl dipeptide (MDP). Here, we investigated the role of Nod2 in the
      development of liver fibrosis. METHODS: We studied experimental cholestatic liver
      disease induced by bile duct ligation or toxic liver disease induced by carbon
      tetrachloride in wild type and Nod2(-/-) mice. RESULTS: Nod2 deficiency protected
      mice from cholestatic but not toxin-induced liver injury and fibrosis. Most
      notably, the hepatic bile acid concentration was lower in Nod2(-/-) mice than
      wild type mice following bile duct ligation for 3 weeks. In contrast to wild type
      mice, Nod2(-/-) mice had increased urinary excretion of bile acids, including
      sulfated bile acids, and an upregulation of the bile acid efflux transporters
      MRP2 and MRP4 in tubular epithelial cells of the kidney. MRP2 and MRP4 were
      downregulated by IL-1beta in a Nod2 dependent fashion. CONCLUSIONS: Our findings
      indicate that Nod2 deficiency protects mice from cholestatic liver injury and
      fibrosis through enhancing renal excretion of bile acids that in turn contributes
      to decreased concentration of bile acids in the hepatocyte.

PMID- 24560661
TI  - Injury to peribiliary glands and vascular plexus before liver transplantation
      predicts formation of non-anastomotic biliary strictures.
AB  - BACKGROUND & AIMS: The peribiliary glands of large bile ducts have been
      identified as a niche of progenitor cells that contribute to regeneration of
      biliary epithelium after injury. We aimed to determine whether injury to the
      peribiliary glands of donor livers is a risk factor for development of non
      anastomotic biliary strictures (NAS) after liver transplantation. METHODS: In 128
      liver transplant procedures, biopsies were taken from the donor bile duct and
      injury was assessed using an established histological grading system.
      Histological severity of injury was subsequently compared in liver grafts that
      later developed biliary structures vs. uncomplicated liver grafts. RESULTS:
      Luminal biliary epithelial loss >50% was observed in 91.8% of the grafts before
      transplantation, yet NAS occurred in only 16.4%. Periluminal peribiliary glands
      were more severely injured than deep peribiliary glands located near the
      fibromuscular layer (>50% loss in 56.9% vs. 17.5%, respectively; p<0.001). Injury
      of deep peribiliary glands was more prevalent and more severe in livers that
      later developed NAS, compared to grafts without NAS (>50% loss in 50.0% vs. 9.8%,
      respectively; p=0.004). In parallel, injury of the peribiliary vascular plexus
      was more severe in livers that developed NAS, compared to grafts without NAS
      (>50% vascular changes in 57.1% vs. 20.3%; p=0.006). CONCLUSION: Injury of
      peribiliary glands and vascular plexus before transplantation is strongly
      associated with the occurrence of biliary strictures after transplantation. This
      suggests that insufficient regeneration due to loss of peribiliary glands or
      impaired blood supply may explain the development of biliary strictures.

PMID- 24560662
TI  - Reply to: "is industrial fructose just a marker of an unhealthy dietary
      pattern?".

PMID- 24560663
TI  - Is industrial fructose just a marker of an unhealthy dietary pattern?

PMID- 24560664
TI  - Response to locoregional treatment and alpha-fetoprotein trend in liver
      transplant candidates for HCC: dwarfs standing on the shoulders of giants.

PMID- 24560666
TI  - Novel synergistic approach to exploit the bactericidal efficacy of commercial
      disinfectants on the biofilms of Salmonella enterica serovar Typhimurium.
AB  - Combined effect of malic acid and ozone as sanitizer to inhibit the biofilm
      formation by Salmonella typhimurium on different food contact surfaces was
      investigated in this study. Different surfaces used in food industry including
      PVC pipes, polyethylene bags, plastic surfaces and fresh produce were analyzed
      for the biofilm formation by S. typhimurium ST1 and ST2. Malic acid alone was not
      able to inhibit biofilm formation in all the samples. However, combination of
      malic acid with ozone reduced the biofilm formation on plastic bags as well as on
      PVC pipes suggesting as an effective disinfectant for food contact surfaces. Five
      and six-fold reduction in biofilm formation was observed in microtitre plates
      after 20 h and 40 h. Scanning electron micrographs of carrot and turnip showed
      control over the biofilms. Malic acid as sanitizer in food industry was effective
      for the complete inhibition of biofilm in carrot and other food contact surfaces,
      besides this, combined sanitizer (malic acid and ozone) was effective in turnip.
      Biofilms in food-processing industries can survive even after the sanitizer
      treatment and may represent reservoirs of product contamination leading to
      subsequent spoilage and/or food safety risks.

PMID- 24560665
TI  - Purification and characterization of an oxygen-evolving photosystem II from
      Leptolyngbya sp. strain O-77.
AB  - A new cyanobacterium of strain O-77 was isolated from a hot spring at Aso-Kuju
      National Park, Kumamoto, Japan. According to the phylogenetic analysis determined
      by 16S rRNA gene sequence, the strain O-77 belongs to the genus Leptolyngbya,
      classifying into filamentous non-heterocystous cyanobacteria. The strain O-77
      showed the thermophilic behavior with optimal growth temperature of 55 degrees C.
      Moreover, we have purified and characterized the oxygen-evolving photosystem II
      (PSII) from the strain O-77. The O2-evolving activity of the purified PSII from
      strain O-77 (PSIIO77) was 1275 +/- 255 MUmol O2 (mg Chl a)(-1) h(-1). Based on
      the results of MALDI-TOF mass spectrometry and urea-SDS-PAGE analysis, the
      purified PSIIO77 was composite of the typical PSII components of CP47, CP43,
      PsbO, D2, D1, PsbV, PsbQ, PsbU, and several low molecular mass subunits. Visible
      absorption and 77 K fluorescence spectra of the purified PSIIO77 were almost
      identical to those of other purified PSIIs from cyanobacteria. This report
      provides the successful example for the purification and characterization of an
      active PSII from thermophilic, filamentous non-heterocystous cyanobacteria.

PMID- 24560669
TI  - miR-107 orchestrates ER stress induction and lipid accumulation by post
      transcriptional regulation of fatty acid synthase in hepatocytes.
AB  - MicroRNAs, a class of small non-coding RNAs, are believed to regulate several
      biological pathways and processes and are implicated in several diseases. They
      mostly regulate the levels of their target genes at the post transcriptional
      stage by primarily binding to the 3' UTR. Elevated hepatic levels of miR-107 are
      a consistent feature associated with several obese and diabetic models. Here, we
      show that miR-107 post-transcriptionally regulates fatty acid synthase (FASN) by
      binding to its 3' UTR and reduces its protein levels and the 3'UTR luciferase
      reporter activity, which are blunted by the miR-107 inhibitor and mutation in the
      miR-107 binding site in the 3' UTR. Knock-down of endogenous miR-107 levels
      increased FASN levels in a dose-dependent manner. Overexpression of miR-107 led
      to significant accumulation of malonyl CoA, accompanied by ER stress induction.
      All these events were prevented in the presence of the miR-107 inhibitor. While
      overexpression of FASN could attenuate miR-107 mediated ER stress markers'
      induction; the ER stress inhibitor, 4-phenyl-butyric acid did not rescue miR-107
      induced FASN inhibition. This was followed by increased triglyceride formation
      and lipid accumulation in the presence of miR-107. These indicate that miR-107
      inhibits FASN levels by binding to its 3' UTR and this interaction promotes ER
      stress induction and malonyl CoA and lipid accumulation in HepG2 cells and
      primary hepatocytes. Our results suggest that increased levels of miR-107 are
      critical in promoting lipid accumulation in hepatocytes and this might form the
      basis of diverse etiologies encountered in a fatty liver. 

PMID- 24560668
TI  - Transmural heterogeneity of cellular level power output is reduced in human heart
      failure.
AB  - Heart failure is associated with pump dysfunction and remodeling but it is not
      yet known if the condition affects different transmural regions of the heart in
      the same way. We tested the hypotheses that the left ventricles of non-failing
      human hearts exhibit transmural heterogeneity of cellular level contractile
      properties, and that heart failure produces transmural region-specific changes in
      contractile function. Permeabilized samples were prepared from the sub
      epicardial, mid-myocardial, and sub-endocardial regions of the left ventricular
      free wall of non-failing (n=6) and failing (n=10) human hearts. Power, an in
      vitro index of systolic function, was higher in non-failing mid-myocardial
      samples (0.59+/-0.06MUWmg(-1)) than in samples from the sub-epicardium (p=0.021)
      and the sub-endocardium (p=0.015). Non-failing mid-myocardial samples also
      produced more isometric force (14.3+/-1.33kNm(-2)) than samples from the sub
      epicardium (p=0.008) and the sub-endocardium (p=0.026). Heart failure reduced
      power (p=0.009) and force (p=0.042) but affected the mid-myocardium more than the
      other transmural regions. Fibrosis increased with heart failure (p=0.021) and mid
      myocardial tissue from failing hearts contained more collagen than matched sub
      epicardial (p<0.001) and sub-endocardial (p=0.043) samples. Power output was
      correlated with the relative content of actin and troponin I, and was also
      statistically linked to the relative content and phosphorylation of desmin and
      myosin light chain-1. Non-failing human hearts exhibit transmural heterogeneity
      of contractile properties. In failing organs, region-specific fibrosis produces
      the greatest contractile deficits in the mid-myocardium. Targeting fibrosis and
      sarcomeric proteins in the mid-myocardium may be particularly effective therapies
      for heart failure. 

PMID- 24560670
TI  - Effect of different culture systems on adipocyte differentiation-related protein
      (ADRP) in bovine embryos.
AB  - Bovine embryos cultured in serum-containing media abnormally accumulate lipid
      droplets, compared to their in vivo counterparts. The objective of this study was
      to investigate the effect of different culture systems on the mRNA expression and
      on the quantification and localisation of adipocyte differentiation-related
      protein (ADRP), a protein associated with lipid accumulation in bovine
      blastocysts. Two experiments were independently performed for ADRP mRNA
      expression analysis. In experiment A, blastocysts were produced in modified
      synthetic oviduct fluid (mSOF)+10% foetal calf serum (FCS), in coculture (bovine
      oviduct epithelial cells, Boec) and in ewe oviducts, whereas in experiment B,
      they were produced in mSOF+10MUM docosahexaenoic acid (DHA) and in vivo. Control
      groups were also performed. ADRP mRNA expression was downregulated in the Boec,
      ewe oviduct and in vivo groups compared to the 10% FCS or DHA groups,
      respectively. Moreover, the expression of this protein was downregulated in the
      Boec group compared to the control group (P<0.05). A third experiment (experiment
      C) was performed to quantify and localise ADRP protein. Boec, in vivo and control
      groups were tested. After immunofluorescence staining followed by confocal
      microscopy analysis, embryonic ADRP was clearly localised around lipid droplets,
      indicating that ADRP is also a lipid droplet coat protein in bovine embryos. In
      conclusion, our results demonstrate that bovine embryos at the blastocyst stage
      expressed ADRP mRNA and protein, and that the embryonic culture system modified
      this expression. 

PMID- 24560667
TI  - PKA turnover by the REGgamma-proteasome modulates FoxO1 cellular activity and
      VEGF-induced angiogenesis.
AB  - The REGgamma-proteasome serves as a short-cut for the destruction of certain
      intact mammalian proteins in the absence of ubiquitin- and ATP. The biological
      roles of the proteasome activator REGgamma are not completely understood. Here we
      demonstrate that REGgamma controls degradation of protein kinase A catalytic
      subunit-alpha (PKAca) both in primary human umbilical vein endothelial cells
      (HUVECs) and mouse embryonic fibroblast cells (MEFs). Accumulation of PKAca in
      REGgamma-deficient HUVECs or MEFs results in phosphorylation and nuclear
      exclusion of the transcription factor FoxO1, indicating that REGgamma is involved
      in preserving FoxO1 transcriptional activity. Consequently, VEGF-induced
      expression of the FoxO1 responsive genes, VCAM-1 and E-Selectin, was tightly
      controlled by REGgamma in a PKA dependent manner. Functionally, REGgamma is
      crucial for the migration of HUVECs. REGgamma(-/-) mice display compromised VEGF
      instigated neovascularization in cornea and aortic ring models. Implanted
      matrigel plugs containing VEGF in REGgamma(-/-) mice induced fewer capillaries
      than in REGgamma(+/+) littermates. Taken together, our study identifies REGgamma
      as a novel angiogenic factor that plays an important role in VEGF-induced
      expression of VCAM-1 and E-Selectin by antagonizing PKA signaling. Identification
      of the REGgamma-PKA-FoxO1 pathway in endothelial cells (ECs) provides another
      potential target for therapeutic intervention in vascular diseases. 

PMID- 24560671
TI  - Impaired colonic motility and reduction in tachykinin signalling in the aged
      mouse.
AB  - Ageing is associated with an increased incidence of constipation in humans. The
      contribution that the ageing process makes to this condition is unclear. The aim
      of this study was to determine the effects of age on faecal output and colonic
      motility in male C57BL/6J mice and to determine the role that altered tachykinin
      signalling plays in this process. Total faecal output recorded over a 24h period
      decreased with age due to a reduction in the number of pellets produced and their
      water content. These changes occurred in the absence of any significant change in
      food and water intake. There was an increase in the amount of faecal matter
      stored in the isolated colon with age which caused a proportional increase in
      colonic length. Analysis of colonic motility using an artificial pellet
      demonstrated that pellets moved in a stepwise fashion through the colon. There
      was an age-related increase in pellet transit time due to decreases in the step
      distance, velocity, and frequency of stepwise movements. These changes were
      reversed using the neurokinin 2 (NK2) receptor agonist neurokinin A. Addition of
      the NK2receptor antagonist GR159897 significantly increased transit time in the
      young animals by decreasing step distance, velocity and frequency, but was
      without effect in the aged colon. In summary, the ageing C57BL/6J mouse shows an
      impaired motility phenotype. These effects appear, at least in part, to be due to
      an attenuation of tachykinin signalling via NK2 receptors. 

PMID- 24560672
TI  - Reduction of spiked porcine circovirus during the manufacture of a Vero cell
      derived vaccine.
AB  - Porcine circovirus-1 (PCV1) was recently identified as a contaminant in live
      Rotavirus vaccines, which was likely caused by contaminated porcine trypsin. The
      event triggered the development of new regulatory guidance on the use of porcine
      trypsin which shall ensure that cell lines and porcine trypsin in use are free
      from PCV1. In addition, manufacturing processes of biologicals other than live
      vaccines include virus clearance steps that may prevent and mitigate any
      potential virus contamination of product. In this work, artificial spiking of
      down-scaled models for the manufacturing process of an inactivated pandemic
      influenza virus vaccine were used to investigate inactivation of PCV1 and the
      physico-chemically related porcine parvovirus (PPV) by formalin and ultraviolet-C
      (UV-C) treatment as well as removal by the purification step sucrose gradient
      ultracentrifugation. A PCV1 infectivity assay, using a real-time PCR infectivity
      readout was established. The formalin treatment (0.05% for 48h) showed
      substantial inactivation for both PCV1 and PPV with reduction factors of 3.0log10
      and 6.8log10, respectively, whereas UV-C treatment resulted in complete PPV
      (>=5.9log10) inactivation already at a dose of 13mJ/cm but merely 1.7log10 at
      24mJ/cm(2) for PCV1. The UV-C inactivation results with PPV were confirmed using
      minute virus of mice (MVM), indicating that parvoviruses are far more sensitive
      to UV-C than PCV1. The sucrose density gradient ultracentrifugation also
      contributed to PCV1 clearance with a reduction factor of 2log10. The low pH
      treatment during the production of procine trypsin was investigated and showed
      effective inactivation for both PCV1 (4.5log10) and PPV (6.4log10). In
      conclusion, PCV1 in general appears to be more resistant to virus inactivation
      than PPV. Still, the inactivated pandemic influenza vaccine manufacturing process
      provides for robust virus reduction, in addition to the already implemented
      testing for PCV1 to avoid any contaminations. 

PMID- 24560673
TI  - Infant 7-valent pneumococcal conjugate vaccine immunization alters young
      adulthood CD4(+)T cell subsets in allergic airway disease mouse model.
AB  - 7-Valent pneumococcal conjugate vaccine (PCV7) immunization in adulthood can
      inhibit allergic asthma in mouse model. The aim of this study is to investigate
      the effects of infant PCV7 immunization on young adulthood CD4(+)T cell subsets
      in a murine allergic airway disease (AAD) model. Our study indicated that infant
      PCV7 immunization can inhibit young adulthood airway inflammation and airway
      hyperresponsiveness (AHR) by inducing the production of Foxp3(+)Treg, Th1 cells
      and their cytokines IL-10 and IFN-gamma, inhibiting the production of Th2, Th17
      cells and their cytokines IL-13 and IL-17A in BALB/c mice model. These results
      suggested that infant PCV7 immunization may serve as an effective measure to
      prevent young adulthood mice AAD. 

PMID- 24560674
TI  - Intranasal vaccination with a replication-deficient influenza virus induces
      heterosubtypic neutralising mucosal IgA antibodies in humans.
AB  - We investigated the cross-neutralising potential of serum and nasal wash samples
      from volunteers who were intranasally immunised once with a monovalent
      replication-deficient delNS1-H1N1 influenza virus vaccine
      (7.7log10TCID50/volunteer). Eight out of twelve (8/12) vaccinees responded to
      vaccination with a significant increase of antibody levels in serum IgG ELISA,
      mucosal IgA ELISA, MNA or HAI. Four responders showed delNS1-specific ELISA IgA
      increases and revealed excellent homosubtypic neutralising activity in serum and
      mucosal washings (4/4). However, 0/4 of the sera but 3/4 of the nasal washings
      neutralised also heterosubtypic H3N2 and H5N1 influenza viruses. Depletion
      experiments proved that IgA but not IgG is responsible for the cross-neutralising
      activity of the nasal wash sample. Our findings indicate that the induction of
      virus-neutralising IgA may represent a valuable correlate of cross-protection of
      intranasal influenza vaccines and that the delNS1 concept constitutes a promising
      approach to protect humans from seasonal and pandemic influenza threats. CLINICAL
      TRIAL REGISTRATION: NCT00724997.

PMID- 24560675
TI  - Inhibition of IFN-gamma promotes anti-asthma effect of Mycobacterium bovis
      Bacillus Calmette-Guerin neonatal vaccination: a murine asthma model.
AB  - OBJECTIVE: The Mycobacterium bovis Bacillus Calmette-Guerin (BCG) neonatal
      vaccination inhibits allergy-induced pathologic changes. However, the mechanisms
      underlying this process are unclear. This study aimed to investigate the role of
      interferon (IFN)-gamma and interleukin (IL)-17 in the protective effects of the
      BCG neonatal vaccination on allergic pulmonary inflammation and airway
      hyperresponsiveness (AHR). METHODS: Wild type (WT)-neonate and IL-17 knock out
      (KO) neonate mice were vaccinated with BCG. A murine asthma model was developed
      by sensitization and then challenging with ovalbumin (OVA). Recombinant IL-17 or
      recombinant IFN-gamma was delivered to the airway to overexpress IL-17 or IFN
      gamma. An anti-IFN-gamma neutralizing antibody was used to block the effects of
      IFN-gamma. RESULTS: We found exogenous IL-17 delivered to the airway reversed the
      anti-asthma effects of the neonatal BCG vaccination. BCG neonatal vaccination
      further reduced OVA-induced inflammation and AHR in IL-17 KO mice. Inhibition of
      IFN-gamma in BCG neonatal vaccinated OVA-induced asthma model mice led to a
      further reduction in airway inflammation and AHR. In addition, airway
      inflammation and AHR were robust following treatment with exogenous IFN-gamma.
      Neutralizing IL-17 was not sufficient to block OVA-induced airway inflammation
      and AHR. In IL-17 KO mice, airway inflammation and AHR did not occur following
      treatment with an anti-IFN-gamma neutralizing antibody. CONCLUSIONS: In an OVA
      induced murine asthma model, inhibition of IFN-gamma enhanced the anti-asthma
      effects of BCG neonatal vaccination.

PMID- 24560676
TI  - Hepatitis B vaccine response among infants born to hepatitis B surface antigen
      positive women.
AB  - PURPOSE: Annually, an estimated 25,000 infants are born to hepatitis B surface
      antigen (HBsAg)-positive women in the United States. Hepatitis B (HepB) vaccine
      and hepatitis B immune globulin (HBIG) are recommended at birth, followed by
      completion of vaccine series and post-vaccination serologic testing (PVST). In a
      large cohort of infants born to HBsAg-positive women, factors influencing vaccine
      response were evaluated. METHODS: Data were from HBsAg-negative infants born to
      HBsAg-positive women in the Enhanced Perinatal Hepatitis B Prevention Program
      (EPHBPP) from 2008 to 2013. Vaccine non-responders were defined as infants with
      antibody to hepatitis B surface antigen (anti-HBs) <10mIU/mL at PVST after
      receiving >=3 vaccine doses. Multivariable analyses modeled statistically
      significant predictor variables associated with non-response. RESULTS: A total of
      17,951 maternal-infant pairs were enrolled; 8654 HBsAg-negative infants born to
      HBsAg-positive mothers received >=3 doses of vaccine with anti-HBs results. 8199
      (94.7%) infants responded to a primary HepB series; 199 (94.8%) to a second
      series. Factors associated with anti-HBs <10mIU/mL included gestational age <37
      weeks, vaccine birth dose >12h after birth, timing of final vaccine dose <6
      months after birth, receipt of 3 vs. 4 vaccine doses, and PVST interval >6 months
      from final vaccine dose in bivariate analysis. PVST interval >6 months from final
      vaccine dose (OR=2.7, CI=2.0, 3.6) was significantly associated with anti-HBs
      <10mIU/mL; the proportion increased from 2% at 1-2 months to 21.6% at 15-16
      months after the final dose. Receipt of a 4th dose improved the response rate
      (OR=0.5, CI=0.3, 0.8). CONCLUSIONS: Ninety-five percent of a large cohort of
      uninfected infants born to HBsAg-positive mothers in the United States responded
      to primary HepB vaccine series. The proportion of infants with anti-HBs <10mIU/mL
      increased with longer interval between the final vaccine dose and PVST. Optimal
      timing of PVST is within 1-2 months of final vaccine dose to avoid unnecessary
      revaccination.

PMID- 24560677
TI  - Comparative quantitative study of astrocytes and capillary distribution in optic
      nerve laminar regions.
AB  - Retinal ganglion cell (RGC) axonal structure and function in the optic nerve head
      (ONH) is predominantly supported by astrocytes and capillaries. There is good
      experimental evidence to demonstrate that RGC axons are perturbed in a non
      uniform manner following ONH injury and it is likely that the pattern of RGC
      axonal modification bears some correlation with the quantitative properties of
      astrocytes and capillaries within laminar compartments. Although there have been
      some excellent topographic studies concerning glial and microvascular networks in
      the ONH our knowledge regarding the quantitative properties of these structures
      are limited. This report is an in-depth quantitative, structural analysis of
      astrocytes and capillaries in the pre laminar, lamina cribrosa and post laminar
      compartments of the ONH. 49 optic nerves from human (n = 10), pig (n = 12), horse
      (n = 6), rat (n = 11) and rabbit (n = 10) eyes are studied. Immunohistochemical
      and high-magnification confocal microscopy techniques are used to co-localise
      astrocytes, capillaries and nuclei in the mid-portion of the optic nerve.
      Quantitative methodology is used to determine the area occupied by astrocyte
      processes, microglia processes, nuclei density and the area occupied by
      capillaries in each laminar compartment. Comparisons are made within and between
      species. Relationships between ONH histomorphometry and astrocyte-capillary
      constitution are also explored. This study demonstrates that there are
      significant differences in the quantitative properties of capillaries and
      astrocytes between the laminar compartments of the human ONH. Astrocyte processes
      occupied the greatest area in the lamina cribrosa compartment of the human ONH
      implicating it as an area of great metabolic demands. Microglia were found to
      occupy only a small proportion of tissue in the rat, rabbit and pig optic nerve
      suggesting that the astrocyte is the predominant glia cell type in the optic
      nerve. This study also demonstrates that there is significant uniformity, with
      respect to astrocyte and capillary constitution, in the post laminar region of
      species with an unmyelinated anterior optic nerve. This implicates an important
      role served by oligodendrocytes and myelin in governing the structural
      characteristics of the post laminar optic nerve. Finally, this study demonstrates
      that eyes with similar lamina cribrosa structure do not necessarily share an
      identical cellular constitution with respect to astrocytes. The quantitative
      properties of astrocytes in the pre laminar and lamina cribrosa regions of the
      rat, which has a rudimentary lamina cribrosa with only a few collagenous beams,
      shared more similarities to the human eye than the pig or horse. The quantitative
      properties of astrocytes and capillaries in the laminar compartments of the ONH
      provide a basis for understanding the pathogenic mechanisms that are involved in
      diseases such as glaucoma and ischemic optic neuropathy. The findings in this
      study also provide valuable information about the distinct advantages of
      different animal models for studying human optic nerve diseases. Utilisation of
      structural data provided in this report together with emerging in vivo technology
      may potentially permit the early identification of RGC axonal injury by
      quantifying changes in ONH capillaries and astrocytes. 

PMID- 24560678
TI  - Source of high-frequency oscillations in oblique saccade trajectory.
AB  - Most common eye movements, oblique saccades, feature rapid velocity, precise
      amplitude, but curved trajectory that is variable from trial-to-trial. In
      addition to curvature and inter-trial variability, the oblique saccade trajectory
      also features high-frequency oscillations. A number of studies proposed the
      physiological basis of the curvature and inter-trial variability of the oblique
      saccade trajectory, but kinematic characteristics of high-frequency oscillations
      are yet to be examined. We measured such oscillations and compared their
      properties with orthogonal pure horizontal and pure vertical oscillations
      generated during pure vertical and pure horizontal saccades, respectively. We
      found that the frequency of oscillations during oblique saccades ranged between
      15 and 40 Hz, consistent with the frequency of orthogonal saccadic oscillations
      during pure horizontal or pure vertical saccades. We also found that the
      amplitude of oblique saccade oscillations was larger than pure horizontal and
      pure vertical saccadic oscillations. These results suggest that the superimposed
      high-frequency sinusoidal oscillations upon the oblique saccade trajectory
      represent reverberations of disinhibited circuit of reciprocally innervated
      horizontal and vertical burst generators. 

PMID- 24560679
TI  - Social network analysis of biomedical research collaboration networks in a CTSA
      institution.
AB  - BACKGROUND: The popularity of social networks has triggered a number of research
      efforts on network analyses of research collaborations in the Clinical and
      Translational Science Award (CTSA) community. Those studies mainly focus on the
      general understanding of collaboration networks by measuring common network
      metrics. More fundamental questions about collaborations still remain unanswered
      such as recognizing "influential" nodes and identifying potential new
      collaborations that are most rewarding. METHODS: We analyzed biomedical research
      collaboration networks (RCNs) constructed from a dataset of research grants
      collected at a CTSA institution (i.e., University of Arkansas for Medical
      Sciences (UAMS)) in a comprehensive and systematic manner. First, our analysis
      covers the full spectrum of a RCN study: from network modeling to network
      characteristics measurement, from key nodes recognition to potential links
      (collaborations) suggestion. Second, our analysis employs non-conventional model
      and techniques including a weighted network model for representing collaboration
      strength, rank aggregation for detecting important nodes, and Random Walk with
      Restart (RWR) for suggesting new research collaborations. RESULTS: By applying
      our models and techniques to RCNs at UAMS prior to and after the CTSA, we have
      gained valuable insights that not only reveal the temporal evolution of the
      network dynamics but also assess the effectiveness of the CTSA and its impact on
      a research institution. We find that collaboration networks at UAMS are not scale
      free but small-world. Quantitative measures have been obtained to evident that
      the RCNs at UAMS are moving towards favoring multidisciplinary research.
      Moreover, our link prediction model creates the basis of collaboration
      recommendations with an impressive accuracy (AUC: 0.990, MAP@3: 1.48 and MAP@5:
      1.522). Last but not least, an open-source visual analytical tool for RCNs is
      being developed and released through Github. CONCLUSIONS: Through this study, we
      have developed a set of techniques and tools for analyzing research collaboration
      networks and conducted a comprehensive case study focusing on a CTSA institution.
      Our findings demonstrate the promising future of these techniques and tools in
      understanding the generative mechanisms of research collaborations and helping
      identify beneficial collaborations to members in the research community.

PMID- 24560680
TI  - FRR: fair remote retrieval of outsourced private medical records in electronic
      health networks.
AB  - Cloud computing is emerging as the next-generation IT architecture. However,
      cloud computing also raises security and privacy concerns since the users have no
      physical control over the outsourced data. This paper focuses on fairly
      retrieving encrypted private medical records outsourced to remote untrusted cloud
      servers in the case of medical accidents and disputes. Our goal is to enable an
      independent committee to fairly recover the original private medical records so
      that medical investigation can be carried out in a convincing way. We achieve
      this goal with a fair remote retrieval (FRR) model in which either t
      investigation committee members cooperatively retrieve the original medical data
      or none of them can get any information on the medical records. We realize the
      first FRR scheme by exploiting fair multi-member key exchange and homomorphic
      privately verifiable tags. Based on the standard computational Diffie-Hellman
      (CDH) assumption, our scheme is provably secure in the random oracle model (ROM).
      A detailed performance analysis and experimental results show that our scheme is
      efficient in terms of communication and computation. 

PMID- 24560681
TI  - Genomic characterization of interferon regulatory factor 5 from rock bream
      (Oplegnathus fasciatus) and its role in antiviral defense.
AB  - The interferon regulatory factor 5 (IRF5) is a key mediator of the Toll-like
      receptor (TLR)7 and TLR8 signaling pathways. In this study, we describe the
      identification of IRF5 (Rb-IRF5) from rock bream fish (Oplegnathus fasciatus) and
      its characteristics features at the genomic and expression levels. The full
      length Rb-IRF5 sequence was identified from a cDNA library and its genomic
      sequence was obtained by screening and sequencing of a bacterial artificial
      chromosome (BAC) genomic DNA library of rock bream. The genomic sequence is
      comprised of 8 exons interrupted by 7 introns. The complete coding sequence of Rb
      IRF5 is 1497 bp in length and encodes for 498 amino acids. The putative Rb-IRF5
      protein consists of 3 important conserved domains: a DNA-binding domain (DBD) at
      the N-terminus, an IRF-associated domain (IAD), and a virus-activated domain
      (VAD) at the C-terminus. Based on pairwise sequence analysis, the highest
      sequence similarity/identity for Rb-IRF5 was observed with the IRF5 gene from
      turbot fish (>87%) and Japanese flounder (83%). Several important putative
      transcription factor-binding sites shared by the IRF gene family, including the
      NF-kappaB, Ap-1, IRF-1, and ICSBP/ISRE sites, were found in the 5' flanking
      region of Rb-IRF5. The predicted tertiary structure of the dimerized IAD and VAD
      of the Rb-IRF5 protein resembled that of its orthologs from humans. In healthy
      rock bream, the highest constitutive expression of Rb-IRF5 was detected in the
      liver. After iridovirus and polyinosinic-polycytidylic acid (poly(I:C))
      challenge, Rb-IRF5 expression was significantly induced in the head kidney.
      Furthermore, rock bream recombinant type I interferon (Rb-IFN1) was also found to
      be an efficient inducer of Rb-IRF5 in a head kidney primary cell culture model.
      Upon IRF5 transfection, rock bream Mx (Rb-Mx), interferon I (Rb-IFN1) and tumor
      necrosis factor alpha (Rb-TNFalpha) genes get significantly upregulated in rock
      bream heart cells. The findings of the present study explain the involvement of
      Rb-IRF5 in the induction of interferons and pro-inflammatory cytokines and
      thereby provide a model for how IRF5 modulates immune responses against viral
      infections in rock bream. 

PMID- 24560682
TI  - Optimal dietary protein/lipid ratio for improved immune status of a newly
      cultivated Mediterranean fish species, the shi drum Umbrina cirrosa, L.
AB  - Shi drum is a new fish species recently cultivated in Greek fish farms. Its
      feeding requirements and health status must be determined in order to optimize
      its culture conditions. The present study looked at the effects of different
      dietary protein levels (47 or 52%) in combination with 3 lipid levels (10, 15 or
      20%) on the immune system of juvenile shi drums. Most immune parameters assessed
      were affected by the dietary treatment. The ceruloplasmin activity, the whole
      blood respiratory burst activity, the serum myeloperoxidase activity, the
      antibacterial activity of serum lysozyme and the serum antiprotease activity all
      varied with the dietary protein/lipid ratio. In view of these results, the lowest
      dietary lipid level tested (10%) was optimal for the immune system of shi drum
      but a clear determination of the optimal dietary protein levels was not obtained
      as 47% reduced stress but also increased the ceruloplasmin response of the fish.
      A dietary lipid level of 10% lipids was recommended for optimal immune status of
      the fish. Dietary protein level of 47% seemed to give better immune responses but
      further study is needed to refine protein requirements. 

PMID- 24560683
TI  - The effects of dietary Immunogen on innate immune response, immune related genes
      expression and disease resistance of rainbow trout (Oncorhynchus mykiss).
AB  - This study investigates the effects of prebiotic Immunogen on lysozyme, TNFalpha
      and HSP70 gene expression in head kidney, humoral innate immune parameters and
      resistant to Aeromonas hydrophila of rainbow trout. 120 healthy rainbow trout
      (81.65 +/- 1.49 g) were distributed in six fiberglass tanks assigned to two
      groups fed control or diet supplemented with 2 g kg(-1) Immunogen for 45 days.
      The results revealed that administration of Immunogen significantly (P < 0.05) up
      regulated lysozyme and TNFalpha gene expression. HSP70 gene expression was
      significantly (P < 0.05) lower in Immunogen fed fish at the end of trial. Humoral
      innate immune parameters (lysozyme activity, ACH50 and bactericidal activity)
      were significantly (P < 0.05) increased whether 15 or 45 days after feeding on
      Immunogen supplemented diet. However, significant (P < 0.05) increase in
      agglutination antibody titer observed just after 45 days feeding on Immunogen.
      Rainbow trout fed with 2 g kg(-1) Immunogen showed remarkably higher resistance
      against A. hydrophila (64.44% survival) compared to the control group (24.44%
      survival). These results confirm that Immunogen can up regulates immune related
      genes expression, stimulates immune response that per se enhances disease
      resistance in rainbow trout.

PMID- 24560684
TI  - Preoperative risk stratification of adnexal masses: can we predict the optimal
      surgical management?
AB  - STUDY OBJECTIVE: To characterize preoperative risk stratification with aim of
      identifying the accurate surgical approach of benign and malignant adnexal masses
      in pediatric patients. DESIGN: A retrospective chart review of all cases of
      adnexal masses surgically managed between January 2001 and December 2006.
      SETTING: The Hospital for Sick Children, Toronto, Canada. PARTICIPANTS: 129 cases
      of 126 pediatric and adolescent patients who underwent operative management of
      their adnexal masses. MAIN OUTCOME MEASURES: Ultrasonographic characteristics
      (cyst size and character), surgical approach (laparoscopy vs laparotomy) and
      method of cyst removal (cystectomy vs oophorectomy). Data was assessed with a
      Fisher Exact test where appropriate (P < .05). RESULTS: Malignancies were more
      frequently treated by laparotomy (n = 14, 98.6%, P < .001), and benign cases by
      laparoscopy (n = 78, 97%, P < .001). On ultrasonography, malignant masses were
      more often complex (n = 16, 100%, P = .006) and >=8 cm (n = 16, 100%, P < .001)
      than benign masses (>=8 cm n = 60, 53%, complex n = 76, 67%). Combining
      ultrasonographic measurements of >=8 cm and complexity identified 100% of
      malignant masses (n = 16) and 36% of benign masses (n = 41, P < .001, PPV = 37.1,
      NPV = 100%). Additional imaging including CT/MRI was ordered by pediatric
      surgeons (n = 17, 77%) more often than pediatric gynecologists (n = 44, 41%, P =
      .002). Furthermore, pediatric surgeons managed adnexal masses by oophorectomy (n
      = 12, 55%) more often as compared to pediatric gynecologists (n = 19, 18%, P <
      .001). CONCLUSION: Using preoperative characteristics of complexity and >=8 cm
      reduces the number of benign masses treated with laparotomy while ensuring
      malignant masses are managed with an open approach.

PMID- 24560685
TI  - Autonomic nerves and perivascular fat: interactive mechanisms.
AB  - The evidence describing the autonomic innervation of body fat is reviewed with a
      particular focus on the role of the sympathetic neurotransmitters. In compiling
      the evidence, a strong case emerges for the interaction between autonomic nerves
      and perivascular adipose tissue (PVAT). Adipocytes have been shown to express
      receptors for neurotransmitters released from nearby sympathetic varicosities
      such as adrenoceptors (ARs), purinoceptors and receptors for neuropeptide Y
      (NPY). Noradrenaline can modulate both lipolysis (via alpha2- and beta3-ARs) and
      lipogenesis (via alpha1- and beta3-ARs). ATP can inhibit lipolysis (via P1
      purinoceptors) or stimulate lipolysis (via P2y purinoceptors). NPY, which can be
      produced by adipocytes and sympathetic nerves, inhibits lipolysis. Thus the
      sympathetic triad of transmitters can influence adipocyte free fatty acid (FFA)
      content. Substance P (SP) released from sensory nerves has also been shown to
      promote lipolysis. Therefore, we propose a mechanism whereby sympathetic
      neurotransmission can simultaneously activate smooth muscle cells in the tunica
      media to cause vasoconstriction and alter FFA content and release from adjacent
      adipocytes in PVAT. The released FFA can influence endothelial function.
      Adipocytes also release a range of vasoactive substances, both relaxing and
      contractile factors, including adiponectin and reactive oxygen species. The
      action of adipokines (such as adiponectin) and reactive oxygen species (ROS) on
      cells of the vascular adventitia and nerves has yet to be fully elucidated. We
      hypothesise a strong link between PVAT and autonomic fibres and suggest that this
      poorly understood relationship is extremely important for normal vascular
      function and warrants a detailed study. 

PMID- 24560687
TI  - [Fernando de Castro. Discoverer of chemoreceptors].

PMID- 24560688
TI  - Chemical kinetics for drug discovery to combat protein aggregation diseases.
AB  - Protein misfolding diseases are becoming increasingly prevalent, yet there are
      very few effective pharmacological treatments. The onset and progression of these
      diseases is associated with the aberrant aggregation of normally soluble proteins
      and peptides into amyloid fibrils. Because genetic and physiological findings
      suggest that protein aggregation is a key event in pathogenesis, an attractive
      therapeutic strategy against this class of disorders is the search for compounds
      able to interfere with this process, in particular by suppressing the formation
      of soluble toxic oligomeric aggregates. In this review, we discuss how chemical
      kinetics can contribute to the fundamental understanding of the molecular
      mechanism of aggregation, and speculate on the implications for the development
      of therapeutic molecules that inhibit specific steps in the aggregation pathway
      that are crucial for preventing toxicity. 

PMID- 24560689
TI  - Proximity of foods in a competitive food environment influences consumption of a
      low calorie and a high calorie food.
AB  - The objective of this study was to test if proximity of a food or preference for
      a food influences food intake in a competitive food environment in which one low
      calorie/low fat (apple slices) and one higher calorie/higher fat (buttered
      popcorn) food was available in the same environment. The proximity of popcorn and
      apple slices was manipulated and 56 participants were randomly assigned to
      groups. In Group Apples Near, apple slices were placed near (within arms reach) a
      participant and popcorn was placed far (2m away). In Group Popcorn Near, buttered
      popcorn was placed near and apple slices were placed far. As a control for the
      absence of a proximity manipulation, Group Both Near had both test foods placed
      near. Although participants rated the popcorn as more liked than apples, the food
      that was placed closer to the participant was consumed most in the two
      experimental groups, regardless of preference (R(2)=0.38). Total energy intake
      was reduced most when popcorn was placed far from a participant compared to when
      it was placed near (R(2)=0.24). The effects reported here were not moderated by
      BMI and did not vary by sex. In all, the results support the hypothesis that
      making a low calorie food more proximate will reduce total energy intake and
      increase intake of a low calorie food, even when a higher calorie and more
      preferred food is also available, but less proximate. 

PMID- 24560690
TI  - Selecting food. The contribution of memory, liking, and action.
AB  - The goal of the present experiment was twofold: identifying similarities and
      differences between flavour memory and visual memory mechanisms and investigating
      whether kinematics could serve as an implicit measure for food selection. To test
      flavour and visual memory an 'implicit' paradigm to represent real-life
      situations in a controlled lab setting was implemented. A target, i.e., a piece
      of cake shaped like either an orange or a tangerine, covered with either orange-
      or a tangerine-flavoured icing, was provided to participants on Day 1. On Day 2,
      without prior notice, participants were requested to recognize the target amongst
      a set of distractors, characterized by various flavours (orange vs. tangerine)
      and/or sizes (orange-like vs. tangerine-like). Similarly, targets and distractors
      consisting of 2D figures varying in shape and size were used to assess visual
      memory. Reach-to-grasp kinematics towards the targets were recorded and analysed
      by means of digitalization techniques. Correlations between kinematic parameters,
      memory and liking for each food item were also calculated. Results concerned with
      memory recollection indices provided evidence of different key mechanisms which
      could be based either on novelty of flavour memory or visual memory,
      respectively. To a moderate extent, kinematics may serve as an implicit index of
      food selection processes. 

PMID- 24560691
TI  - Accuracy of the Microsoft Kinect sensor for measuring movement in people with
      Parkinson's disease.
AB  - BACKGROUND: The Microsoft Kinect sensor (Kinect) is potentially a low-cost
      solution for clinical and home-based assessment of movement symptoms in people
      with Parkinson's disease (PD). The purpose of this study was to establish the
      accuracy of the Kinect in measuring clinically relevant movements in people with
      PD. METHODS: Nine people with PD and 10 controls performed a series of movements
      which were measured concurrently with a Vicon three-dimensional motion analysis
      system (gold-standard) and the Kinect. The movements included quiet standing,
      multidirectional reaching and stepping and walking on the spot, and the following
      items from the Unified Parkinson's Disease Rating Scale: hand clasping, finger
      tapping, foot, leg agility, chair rising and hand pronation. Outcomes included
      mean timing and range of motion across movement repetitions. RESULTS: The Kinect
      measured timing of movement repetitions very accurately (low bias, 95% limits of
      agreement <10% of the group mean, ICCs >0.9 and Pearson's r>0.9). However, the
      Kinect had varied success measuring spatial characteristics, ranging from
      excellent for gross movements such as sit-to-stand (ICC=.989) to very poor for
      fine movement such as hand clasping (ICC=.012). Despite this, results from the
      Kinect related strongly to those obtained with the Vicon system (Pearson's r>0.8)
      for most movements. CONCLUSIONS: The Kinect can accurately measure timing and
      gross spatial characteristics of clinically relevant movements but not with the
      same spatial accuracy for smaller movements, such as hand clasping.

PMID- 24560686
TI  - Brain-derived neurotrophic factor in the airways.
AB  - In addition to their well-known roles in the nervous system, there is increasing
      recognition that neurotrophins such as brain derived neurotrophic factor (BDNF)
      as well as their receptors are expressed in peripheral tissues including the
      lung, and can thus potentially contribute to both normal physiology and
      pathophysiology of several diseases. The relevance of this family of growth
      factors lies in emerging clinical data indicating altered neurotrophin levels and
      function in a range of diseases including neonatal and adult asthma, sinusitis,
      influenza, and lung cancer. The current review focuses on 1) the importance of
      BDNF expression and signaling mechanisms in early airway and lung development,
      critical to both normal neonatal lung function and also its disruption in
      prematurity and insults such as inflammation and infection; 2) how BDNF,
      potentially derived from airway nerves modulate neurogenic control of airway
      tone, a key aspect of airway reflexes as well as dysfunctional responses to
      allergic inflammation; 3) the emerging idea that local BDNF production by
      resident airway cells such as epithelium and airway smooth muscle can contribute
      to normal airway structure and function, and to airway hyperreactivity and
      remodeling in diseases such as asthma. Furthermore, given its pleiotropic effects
      in the airway, BDNF may be a novel and appealing therapeutic target. 

PMID- 24560692
TI  - Persistent lone atrial fibrillation: clinicopathologic study of 19 cases.
AB  - BACKGROUND: The extent to which atrial myocardium is remodeled in patients with
      persistent lone atrial fibrillation (LAF) is largely unknown. OBJECTIVE: The
      purpose of this study was to perform a clinicopathologic investigation in
      patients with persistent LAF. METHODS: We characterized structural and molecular
      remodeling in atrial biopsies from 19 patients (17 males, mean age 49 years) with
      persistent (>7 days; n = 8) or long-lasting persistent (>1 year; n = 11) LAF who
      underwent surgical ablation. Atrial tissue from 15 autopsy samples without
      clinicopathologic evidence of heart disease served as controls. RESULTS:
      Morphometric analysis showed cardiomyocyte hypertrophy and greater amounts of
      myolytic damage and interstitial fibrosis in persistent LAF patients compared to
      controls (P <.0001). Atrial tissue levels of heme oxygenase-1 and 3-nitrotyrosine
      were increased in persistent LAF patients (P <.001), consistent with oxidative
      stress. Levels of superoxide dismutase-2, interleukin-8, interleukin-10, tumor
      necrosis factor-alpha, and thiobarbituric acid reactive substance were greater in
      controls than in persistent LAF patients. Immunoreactive signal for connexin43
      was reduced more frequently in persistent LAF patients than controls. There was
      no correlation between features of structural or molecular remodeling and
      clinical parameters, including persistent LAF duration. CONCLUSION: In persistent
      LAF patients, the atria are modified by structural remodeling and molecular
      changes of oxidative stress. Tissue changes in persistent LAF appear to occur
      early after its onset and are qualitatively no different than those observed in
      patients with atrial fibrillation related to conventional risk factors. These
      findings suggest that different types of atrial fibrillation are associated with
      the same spectrum of tissue lesions. Early intervention to restore sinus rhythm
      in persistent LAF patients may prevent irreversible tissue change, especially
      interstitial fibrosis.

PMID- 24560693
TI  - Leisure-time physical activity predicts complaints of snoring in women: a
      prospective cohort study over 10 years.
AB  - OBJECTIVE: We aimed to assess the impact of self-reported physical activity on
      incidence and remission of snoring complaints in women. METHODS: A population
      based sample of 4851 women aged >20 years responded to questionnaires in years
      2000 and 2010. Based on the responses, the women were categorized into low,
      medium, or high level of physical activity at baseline and at follow-up. RESULTS:
      The prevalence of habitual snoring complaints increased from 7.6% at baseline to
      9.2% in 2010 (P<.0001). After adjusting for age, body mass index (BMI), waist and
      neck circumference, weight gain, smoking status, alcohol dependence, and snoring
      status at baseline, reported physical activity level at baseline had a protective
      effect on habitual snoring complaints at follow-up. The adjusted odds ratio (OR)
      (95% confidence intervals) for complaints of habitual snoring was 0.7 (0.5-0.9)
      for the reported medium physical activity level and 0.5 (0.4-0.8) for the high
      activity level. When subdividing the population by changes in reported physical
      activity level over the follow-up period, an increase in physical activity was
      followed by a decrease in the complaint of snoring. Similarly a high level of
      reported physical activity only had a protective effect on snoring in
      participants who remained at a high or medium level. CONCLUSIONS: A low level of
      self-reported physical activity is a risk factor for future habitual snoring
      complaints in women, independent of weight, weight gain, alcohol dependence, and
      smoking. Increased physical activity can modify the risk.

PMID- 24560694
TI  - Structural analysis and identification of PhuS as a heme-degrading enzyme from
      Pseudomonas aeruginosa.
AB  - Bacterial pathogens require iron for proliferation and pathogenesis. Pseudomonas
      aeruginosa is a prevalent Gram-negative opportunistic human pathogen that takes
      advantage of immunocompromised hosts and encodes a number of proteins for uptake
      and utilization of iron. Here we report the crystal structures of PhuS,
      previously known as the cytoplasmic heme-trafficking protein from P. aeruginosa,
      in both the apo- and the holo-forms. In comparison to its homologue ChuS from
      Escherichia coli O157:H7, the heme orientation is rotated 180 degrees  across the
      alpha-gamma axis, which may account for some of the unique functional properties
      of PhuS. In contrast to previous findings, heme binding does not result in an
      overall conformational change of PhuS. We employed spectroscopic analysis and CO
      measurement by gas chromatography to analyze heme degradation, demonstrating that
      PhuS is capable of degrading heme using ascorbic acid or cytochrome P450
      reductase-NADPH as an electron donor and produces five times more CO than ChuS.
      Addition of catalase slows down but does not stop PhuS-catalyzed heme
      degradation. Through spectroscopic and mass spectrometry analysis, we identified
      the enzymatic product of heme degradation to be verdoheme. These data taken
      together suggest that PhuS is a potent heme-degrading enzyme, in addition to its
      proposed heme-trafficking function. 

PMID- 24560695
TI  - The value of total protein in guiding management of infectious parapneumonic
      effusion by using matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry.
AB  - BACKGROUND/PURPOSE: Infectious parapneumonic effusion (PE) contains proteins
      originating from circulation as well as proteins locally released by inflammatory
      pulmonary cells. The purpose of this study was to investigate the value of total
      protein analysis in guiding management of infectious PE by using matrix-assisted
      laser desorption/ionization time-of-flight mass spectrometry. METHODS: Fifty
      seven children with pneumonia followed by PE were consecutively enrolled into our
      study. Protein profiles generated by matrix-assisted laser desorption/ionization
      time-of-flight mass spectrometry after fractionating samples with functionalized
      magnetic beads (C8) were used for differentiating complicated PE (CPE) from non
      CPE. A training set was used to generate classification models and the clinical
      efficacy of these models in detecting CPE and the need for intervention was then
      evaluated in an independent set. RESULTS: The MS spectra derived from PE were
      analyzed, and classification models were constructed in the training set. A total
      of 123 mass/charge (m/z) values were identified and 23 m/z values which were
      significant with p < 0.05 were used as classifiers. An optimized genetic
      algorithm model containing enforced selection of three significant downregulated
      m/z values (2127, 2232, and 2427) was able to classify CPE with 100% positive
      predictive value and predict the need of aggressive therapeutic intervention with
      77% positive predictive value. CONCLUSION: A diagnostic model construction
      comprising three potential biomarkers can predict CPE and need for surgical
      intervention rapidly and precisely. Pleural fluid proteins downregulated during
      the progression of pneumonia could potentially guide the management of infectious
      PE.

PMID- 24560696
TI  - How quickly can conventional organism identification deliver reports for positive
      blood cultures in real life?

PMID- 24560697
TI  - Cleavage site stability of Egyptian highly pathogenic avian influenza viruses in
      backyard chickens during 2009-2011.
AB  - PURPOSE: Two distinguishable subclades of H5N1 (classic and variant strains) are
      cocirculating among the poultry populations in Egypt despite the intensive
      vaccination programs. A study to investigate the genetic relationship between
      avian influenza virus (AIV) isolates from backyard chickens in Sharkia (2009
      2011), subclades, and commercially available vaccines was carried out. METHODS:
      Forty-eight suspected AIV infected birds were clinically examined and used for
      virus isolation followed by reverse transcription-polymerase chain reaction. Four
      H5N1 virus isolates were sequenced and analyzed. The intravenous pathogenicity
      index (IVPI) of three AIV isolates was determined. RESULTS: Thirty-four
      hemagglutinating viral agents (30 AIV subtype H5N1 and 4 Newcastle disease virus)
      were detected. Both the nucleotide and amino acid sequence identities of four
      H5N1 virus isolates (SHZA-0412/2009, SHZA-0801/2010, SHMK-1903/2010, and SHAH
      1403/2011) were high--98.4-99.7% and 100%, respectively--indicative of their
      genetic homogeneity. The hemagglutinin cleavage site characterization revealed
      the presence of multiple basic amino acids (-PQRERRRKKR/GL-) of the highly
      pathogenic phenotype. These results were supported by IVPI in chickens of 2.69
      2.90. The similarity of our isolates with H5N1 AIV vaccine strains (93.9-95.1%)
      was higher than that with H5N2 strains (77.8-91.9%). The divergence of four
      sequences with classic and variant lineages is 2-2.7% and 2.3-3%, respectively,
      with two amino acid substitutions (A249P and N251Y). CONCLUSION: Genetic
      characterization and IVPI data of backyard H5N1 isolates are indicative of a
      highly pathogenic avian influenza virus with hemagglutinin cleavage site
      constancy and two amino acids substitutions with Egyptian classic and variant
      lineages, suggesting a beginning of antigenic drift.

PMID- 24560698
TI  - Empyema necessitatis due to Mycobacterium tuberculosis.

PMID- 24560699
TI  - Antineutrophil cytoplasmic antibody-associated vasculitis in Taiwan: A hospital
      based study with reference to the population-based National Health Insurance
      database.
AB  - BACKGROUND: Antineutrophil cytoplasmic antibody-associated vasculitis (AAV),
      including granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA),
      and Churg-Strauss syndrome (CSS), comprises a group of diseases with significant
      morbidity and mortality. The incidence and relative frequency of GPA/MPA/CSS are
      different all over the world. The epidemiology of AAV in Taiwan is still not
      clear. METHODS: The current study aimed to provide a population-based estimate of
      the annual incidence of GPA using the Taiwan National Health Insurance (NHI)
      research database and a single hospital-based estimate of the relative frequency
      of AAV in Taiwan. RESULTS: The annual incidence of GPA in Taiwan was 0.37 per
      million patient-years (95% Poisson rate confidence interval: 0.30-0.45) from 1997
      to 2008, according to the NHI database. In our hospital, 24 patients were newly
      diagnosed with AAV between 2003 and 2011, including eight patients with GPA, 14
      with MPA, and two with CSS. The ratio of the number of patients with GPA to that
      of MPA was 0.57. CONCLUSION: The current results provide an estimate of the
      annual incidence of GPA and the relative frequency of AAV in the Chinese Han
      community in Taiwan. Such geoepidemiology information may help illuminate the
      interaction between ethnic background and environment in these autoimmune
      diseases.

PMID- 24560700
TI  - Development of antiviral agents toward enterovirus 71 infection.
AB  - Enterovirus 71 (EV71) infection remains a public health problem at a global
      level, particularly in the Asia-Pacific region. The infection normally manifests
      as hand-foot-mouth disease; however, it is capable of developing into potentially
      fatal neurological complications. There is currently no approved vaccine or
      antiviral substance available for the prevention or treatment of EV71 infection.
      This paper, thus, reviews efforts to develop or discover synthetic as well as
      naturally occurring compounds directed against EV71 infection. The recent
      achievements in cellular receptors of EV71 are also highlighted, and their
      contribution to the development of antiviral drugs against EV71 is discussed in
      this article. 

PMID- 24560701
TI  - EMAS position statements and clinical guides.

PMID- 24560703
TI  - NMDA receptor-dependent multidendrite Ca(2+) spikes required for hippocampal
      burst firing in vivo.
AB  - High-frequency bursts of action potentials (APs) are a distinctive form of
      signaling in various types of mammalian central neurons. In CA1 hippocampal
      pyramidal neurons in vivo, such complex spike bursts (CSs) are detected during
      various behaviors and are considered to be particularly important for learning-
      and memory-related synaptic plasticity. Here, we combined whole-cell recordings
      and two-photon imaging in mouse CA1 pyramidal neurons to investigate the cellular
      mechanisms underlying CSs in vivo. Our results demonstrate that CSs are of
      synaptic origin, as they require N-methyl-D-aspartate (NMDA) receptor activation.
      We identify voltage-gated Ca(2+) channel-dependent, spike-like depolarizations as
      integral components of the CSs. These Ca(2+) spikes were invariably associated
      with widespread large-amplitude Ca(2+) transients in basal and apical dendrites.
      Together, our results reveal a type of NMDA receptor-dependent multidendrite
      Ca(2+) spike required for high-frequency bursting in vivo. 

PMID- 24560702
TI  - A transcription factor network coordinates attraction, repulsion, and adhesion
      combinatorially to control motor axon pathway selection.
AB  - Combinations of transcription factors (TFs) instruct precise wiring patterns in
      the developing nervous system; however, how these factors impinge on surface
      molecules that control guidance decisions is poorly understood. Using mRNA
      profiling, we identified the complement of membrane molecules regulated by the
      homeobox TF Even-skipped (Eve), the major determinant of dorsal motor neuron
      (dMN) identity in Drosophila. Combinatorial loss- and gain-of-function genetic
      analyses of Eve target genes indicate that the integrated actions of attractive,
      repulsive, and adhesive molecules direct eve-dependent dMN axon guidance.
      Furthermore, combined misexpression of Eve target genes is sufficient to
      partially restore CNS exit and can convert the guidance behavior of interneurons
      to that of dMNs. Finally, we show that a network of TFs, comprised of eve, zfh1,
      and grain, induces the expression of the Unc5 and Beaten-path guidance receptors
      and the Fasciclin 2 and Neuroglian adhesion molecules to guide individual dMN
      axons. 

PMID- 24560704
TI  - Changes in the responsiveness of hypothalamic prokineticin 2 mRNA expression to
      food deprivation in developing female rats.
AB  - Prokineticin 2 (PK2) is highly expressed in several regions of the central
      nervous system, including the hypothalamus. Recently, it has been suggested that
      PK2 plays a role in appetite regulation. In adult male rodents, the
      administration of PK2 decreased food intake, and PK2 mRNA expression was reduced
      by food deprivation. Usually, the changes in the expression levels of appetite
      regulating factors induced in response to fasting are not fully established
      during the neonatal period. Thus, we investigated the developmental changes in
      hypothalamic PK2 mRNA expression and the alterations in hypothalamic PK2 mRNA
      expression induced by fasting during the pre-pubertal period in female rats. The
      changes in hypothalamic neuropeptide Y (NPY) mRNA expression were also examined
      because NPY is a potent appetite regulatory factor. Hypothalamic PK2 mRNA
      expression was extremely high during the early neonatal period (postnatal day
      (PND) 5) compared with that observed during subsequent periods (PND15, 25, and
      42), while hypothalamic NPY mRNA expression did not differ among any of the
      examined periods. A fasting-induced reduction in hypothalamic PK2 mRNA expression
      was observed on PND5, but no fasting-induced increase in hypothalamic NPY mRNA
      expression was seen during the same period. In addition, the fasting-induced
      reduction in hypothalamic PK2 mRNA expression observed on PND5 was more marked
      than that seen on PND25. These results suggest that the sensitivity of
      hypothalamic PK2 expression to undernutrition develops during the early neonatal
      period, when the responses of other appetite regulatory factors to such pressures
      remain immature. 

PMID- 24560705
TI  - Acute lung injury in patients with subarachnoid hemorrhage: a nationwide
      inpatient sample study.
AB  - OBJECTIVE: To determine national trends for patients with subarachnoid hemorrhage
      (SAH) and pulmonary complications including acute respiratory distress syndrome
      (ARDS). METHODS: The Nationwide Inpatient Sample database was used to sample
      193,209 admissions for SAH with and without ARDS during the period 1993-2008
      using International Classification of Diseases, Ninth Revision, Clinical
      Modification coding. A multivariate stepwise regression analysis was performed.
      RESULTS: The incidence of ARDS in patients with SAH increased from 35.51% in 1993
      to 37.60% in 2008. However, the overall mortality in patients with SAH and in
      patients with SAH and ARDS decreased in the same period, from 42.30% to 31.99%
      and from 75.13% to 60.76%, respectively. Multivariate analysis showed that the
      predictors of developing ARDS in patients with SAH include older age; larger
      hospital size; and comorbidities such as epilepsy, cardiac arrest, sepsis,
      congestive heart failure, hypertension, chronic obstructive pulmonary disease,
      hematologic dysfunction, renal dysfunction, and neurologic dysfunction.
      Predictors of mortality in patients with SAH include age and hospital
      complications, such as coronary artery disease, ARDS, cancer, hematologic
      dysfunction, and renal dysfunction. CONCLUSIONS: Patients with SAH are at
      increased risk of developing ARDS. The identification of certain risk factors may
      alert and aid practitioners in preventing worsening disease.

PMID- 24560706
TI  - Efficacy of placing a thin layer of gelatin sponge over the subdural space during
      dural closure in preventing meningo-cerebral adhesion.
AB  - OBJECTIVE: One significant drawback during a cranial reoperation is the presence
      of meningocerebral adhesions. The appearance of connective tissue bridges between
      the inner surface of the dura and the pia-arachnoid is mostly related to dural
      closure and the condition in which the surgical field was left in the previous
      surgery. This study was done to determine the benefit of placing a thin-layer
      gelatin sponge of polypeptides subdurally to prevent meningocerebral adhesions.
      METHODS: From September 2005 through May 2012, 902 craniotomies were performed
      for various lesions by the senior author (U.T.). Beginning in February 2009, we
      began placing a gelatin sponge under the dural flap to isolate the dural healing
      process from the cortical surface. To compare the degree of meningocerebral
      adhesions statistically, reoperation cases between February 2009 and May 2012
      were divided into 2 groups as group G (gelatin) and group C (Control) in which
      the dural closure was made with and without subdural application of the gelatin
      sponge, respectively. RESULTS: In all patients of group G (n = 15), a neomembrane
      was found when the dura was opened. This layer was easily dissected and showed no
      or minimal attachment to the underlying cerebral cortex. However, in group C (n =
      14), meningocerebral adhesions in various degrees were detected. Adhesion scores
      were significantly greater in group C than in group G (P < 0.001). CONCLUSION:
      This study proves that, during the dural closure, placing a thin layer of gelatin
      sponge in the subdural space is a safe and effective method for preventing
      meningocerebral adhesions.

PMID- 24560707
TI  - Medieval times' influencing figure Rhaze's approach to head injuries in Liber
      Almansoris.
AB  - OBJECTIVE: To present the chapter "On wound of the head and fracture of the head
      bone" of Kitab al-Mansuri / Liber Almansoris, which was one of the early works of
      Rhazes. METHODS: Both Arabic (Suleymaniye Manuscript Library, Ayasofya
      collection, Nr. 3751 and Millet Library, Feyzullah Efendi collection, Nr. 1327)
      and the Latin (Basileae, 1544) texts of Kitab al-Mansuri / Liber Almansoris were
      studied, and the 26th section of the 7th chapter, entitled "Fi al-shajja kasr al
      'azm al-ra's / De plagis capitis et fractura cranei / On wound of the head and
      fracture of the head bone" was translated into English and English text created.
      RESULTS: Rhazes underlined removing bone fragments in depressed and separated
      fractures of cranium along with protection of the dura, but he did not describe
      any surgical technique in this chapter. CONCLUSIONS: Galen's contemplation for
      the care of the dura with its integrity and as well his proposal to remove the
      bone fragments for preventing the dura from injury were the golden standards at
      the time that Rhazes also followed in the treatment of skull fractures.

PMID- 24560708
TI  - Preservation of labyrinthine structures while drilling the posterior wall of the
      internal auditory canal in surgery of vestibular schwannomas via the retrosigmoid
      suboccipital approach.
AB  - OBJECTIVE: To describe a new technique for safe drilling of the posterior wall of
      the internal auditory canal (IAC), in which the intact posterior lip of the
      internal auditory meatus is used as a fixed intraoperative reference point to
      preserve the integrity of labyrinthine structures. METHODS: The retrosigmoid
      suboccipital approach was used to operate on 6 cases of vestibular schwannomas
      (Koos grade I and II), with preserved hearing. On a preoperative high-resolution
      computed tomography scan, a line starting 2 cm lateral to the lateral edge of the
      sigmoid sinus on the dura mater and directed tangential to the posterior
      semicircular canal or common crus was identified to intersect the posterior wall
      of the IAC. Drilling was carried out at a measured angle to the posterior petrous
      wall for meticulously measured distances, taking the intact posterior lip of the
      internal auditory meatus as a fixed bony point. RESULTS: In the 6 cases, the mean
      length of the posterior wall of the IAC measured on the preoperative high
      resolution computed tomography scan was 10.79 mm+/-1.87. By using our technique,
      the percentage of total length of the posterior wall of IAC drilled was 75.3%+/
      20.5%. No injury to the posterior semicircular canal or common crus was observed
      intraoperatively. Total excision was performed in 5 patients, and near-total
      excision was performed in 1 patient. Functional hearing was preserved in all
      patients; testing was done 1 month after surgery. CONCLUSIONS: Adequate drilling
      of the posterior wall of the IAC could be achieved, and tumor excision with
      hearing preservation was obtained by meticulous intraoperative planning and
      measurements based on preoperative computed tomography scanning and by keeping
      the intact posterior lip of the internal auditory meatus as a landmark for safe
      drilling.

PMID- 24560709
TI  - Management of low-grade gliomas: a review of patient-perceived quality of life
      and neurocognitive outcome.
AB  - Low-grade glioma (LGG) comprises nearly 20% of all central nervous system glial
      tumors, with approximately 2000-3000 patients diagnosed annually in the United
      States. Because of their infiltrative ability and aggressive nature, the average
      10-year survival is 30% when <90% of the tumor is resected. Since the 1970s,
      prognosis for LGGs has improved significantly. This improvement is primarily
      attributable to earlier diagnoses via magnetic resonance imaging scanning,
      increased awareness of the more favorable oligo component, technical advances in
      intraoperative neurosurgery, and stratification for young age. Using a number of
      prognostic factors, LGGs have been classified into low-risk and high-risk
      subgroups. Optimal therapy for patients with low-risk, supratentorial grade II
      glioma remains a highly controversial issue in the neuro-oncology community. The
      concerns regarding the toxicity of therapy often outweigh the benefits of
      delaying tumor progression. The recommendation for observation is made without
      full prospective understanding of the impact of radiologic tumor progression on
      the quality of life (QOL), neurocognitive function (NCF), seizure control, and
      functional status of these patients. We present a review of the current knowledge
      of the management of LGG with emphasis upon patient-reported outcomes of QOL,
      NCF, and seizure control. We also discuss current clinical trials with proposals
      to evaluate QOL, NCF, and seizure control in patients undergoing observation
      alone after newly diagnosed low-risk LGG or treatment options for those patients
      in the high-risk group.

PMID- 24560710
TI  - Readmissions in neurosurgery: a qualitative inquiry.
AB  - OBJECTIVE: To identify deficiencies leading to readmissions to the University of
      Florida Neurosurgery Service by using the Institute for Healthcare Improvement
      STate Action on Avoidable Rehospitalizations Readmissions diagnostic tool and to
      report the opinions of patients, their families, and health care providers.
      METHODS: A retrospective review of hospital admission and discharge data was
      conducted. All patients who met eligibility criteria and who were discharged from
      the neurosurgery service between January 1 and March 31, 2012, and readmitted
      within 30 days after discharge (n=74; 66 patients; 7 multiple readmissions) were
      included. A chart review revealed potential precipitating factors. Health care
      providers, patients, and family members were also interviewed. Median values and
      frequencies were used to summarize the data. RESULTS: The 30-day readmission rate
      on the neurosurgery service was 14%. Problems associated with wound care
      accounted for 24% of readmissions, neurologic conditions accounted for 50%, and
      other medical conditions accounted for 26%. Patients and providers agreed on the
      medical diagnoses resulting in readmission, but providers also often named
      "patient noncompliance" as a factor leading to readmission, whereas patients
      often thought they either were "sent home too early" or had a "general decline
      with no improvement." CONCLUSIONS: Systematic patterns and common themes
      associated with patient readmissions were identified for a neurosurgical service.
      These findings are now being used to implement changes in discharge planning.

PMID- 24560711
TI  - Bypass using V2-V3 segment of the vertebral artery as donor or recipient:
      technical nuances and results.
AB  - OBJECTIVE: Surgical revascularization (bypass) technique has been used to treat
      vascular diseases of the posterior circulation, including ischemia, aneurysms,
      and tumors encasing a major artery. We focused on procedures using the V2-V3
      segment of the vertebral artery (VA) as either the donor or recipient of the
      bypass. We have described technical nuances developed over time and evaluated the
      surgical results of those cases. METHODS: Data on all patients who underwent
      bypasses using the V2-V3 segment were collected retrospectively from a
      prospectively maintained database. RESULTS: Twenty patients had bypasses using V2
      V3 distal VA as either the donor (13) or recipient (7); 19 patients had an
      intervening graft and in 1 patient, the VA was used for reimplantation of the
      posterior inferior cerebellar artery. Except for 1 patient, who died during the
      perioperative period, the mean follow-up time for the rest of the patients was
      24.7 months (range 1-72 months). One patient developed postoperative stroke. One
      radial artery graft occluded, and a redo saphenous vein graft also occluded in
      the same patient. All the other bypasses were patent without flow limitation at
      the latest follow-up. Fourteen patients had a modified Rankin Scale score of 2 or
      better at the latest follow-up, and 2 died of unrelated causes as the result of
      their tumors. CONCLUSIONS: The V2-V3 segment of the VA can be used both as a
      donor and a recipient for bypass surgery. Using the technical steps perfected
      over time, we are able to achieve surgical results with high rate of graft
      patency and good functional outcome in patients.

PMID- 24560712
TI  - Rationally optimized cryopreservation of multiple mouse embryonic stem cell
      lines: II--Mathematical prediction and experimental validation of optimal
      cryopreservation protocols.
AB  - In Part I, we documented differences in cryopreservation success measured by
      membrane integrity in four mouse embryonic stem cell (mESC) lines from different
      genetic backgrounds (BALB/c, CBA, FVB, and 129R1), and we demonstrated a
      potential biophysical basis for these differences through a comparative study
      characterizing the membrane permeability characteristics and osmotic tolerance
      limits of each cell line. Here we use these values to predict optimal
      cryoprotectants, cooling rates, warming rates, and plunge temperatures. We
      subsequently verified these predictions experimentally for their effects on post
      thaw recovery. From this study, we determined that a cryopreservation protocol
      utilizing 1M propylene glycol, a cooling rate of 1 degrees C/minute, and plunging
      into liquid nitrogen at -41 degrees C, combined with subsequent warming in a 22
      degrees C water bath with agitation, significantly improved post-thaw recovery
      for three of the four mESC lines, and did not diminish post-thaw recovery for our
      single exception. It is proposed that this protocol can be successfully applied
      to most mESC lines beyond those included within this study once the effect of
      propylene glycol on mESC gene expression, growth characteristics, and germ-line
      transmission has been determined. Mouse ESC lines with poor survival using
      current standard cryopreservation protocols or our proposed protocol can be
      optimized on a case-by-case basis using the method we have outlined over two
      papers. For our single exception, the CBA cell line, a cooling rate of 5 degrees
      C/minute in the presence of 1.0M dimethyl sulfoxide or 1.0M propylene glycol,
      combined with plunge temperature of -80 degrees C was optimal.

PMID- 24560713
TI  - Coupling of serotonergic input to NMDA receptor-phosphorylation following
      peripheral nerve injury via rapid, synaptic up-regulation of ND2.
AB  - Evidence implicates serotonergic input to spinal dorsal horn neurons in shifting
      the NMDA receptor (NMDAR) into a high functional output profile after spinal
      nerve ligation (SNL). We investigated the involvement of adaptor protein NADH
      dehydrogenase subunit 2 (ND2) in NMDAR-phosphorylation and spinal
      hyperexcitability secondary to peripheral nerve injury. Immunofluorescence for
      ND2 was found in dorsal horn neurons immunopositive for NMDAR subunit NR1. Co
      localization of ND2 with postsynaptic marker PSD-95 was significantly increased
      60min after SNL (Rr 0.77 vs Rr 0.06 in sham controls; z=-242.85; p<0.01 at
      Fisher's exact test). Western blot analyses confirmed ND2 up-regulation both in
      cytoplasmic (S2) and synaptic (P3) compartments (p<0.01 at the Student's t test).
      SNL was followed by increased co-localization of ND2 with the phosphorylated form
      (serine 896) of NR1 (pNMDA). Spinal superfusion with ND2 inhibitor rotenone
      prevented up-regulation of ND2 (Rr 0.06 after rotenone vs Rr 0.78 in vehicle
      treated controls, z=-253.22, p<0.01) and pNR1 in P3. C fiber-evoked dorsal horn
      field potentials were increased 60min after SNL by superfusion with NMDA agonist
      cis-ACPD at 100nM (p<0.01 at the Bonferroni test), however cis-ACPD was effective
      only at 10MUM following prior administration of rotenone. Rotenone also abolished
      enhancement of evoked potentials induced by simultaneous stimulation of NMDA and
      5-HR2B receptors in uninjured rats. Increased postsynaptic up-regulation of
      ND2/pNMDAR 60min after SNL was prevented by prior administration of selective 5
      HT2B antagonist SB204741. These results support a pivotal role for ND2 in
      coupling serotonergic input to NMDAR-activation during neuropathic pain. 

PMID- 24560714
TI  - Acute exercise prevents the development of neuropathic pain and the sprouting of
      non-peptidergic (GDNF- and artemin-responsive) c-fibers after spinal cord injury.
AB  - Spinal cord injury (SCI) impaired sensory fiber transmission leads to chronic,
      debilitating neuropathic pain. Sensory afferents are responsive to neurotrophic
      factors, molecules that are known to promote survival and maintenance of neurons,
      and regulate sensory neuron transduction of peripheral stimuli. A subset of
      primary afferent fibers responds only to the glial cell-line derived neurotrophic
      factor (GDNF) family of ligands (GFLs) and is non-peptidergic. In peripheral
      nerve injury models, restoration of GDNF or artemin (another GFL) to pre-injury
      levels within the spinal cord attenuates neuropathic pain. One non-invasive
      approach to increase the levels of GFLs in the spinal cord is through exercise
      (Ex), and to date exercise training is the only ameliorative, non-pharmacological
      treatment for SCI-induced neuropathic pain. The purpose of this study was 3-fold:
      1) to determine whether exercise affects the onset of SCI-induced neuropathic
      pain; 2) to examine the temporal profile of GDNF and artemin in the dorsal root
      ganglia and spinal cord dorsal horn regions associated with forepaw dermatomes
      after SCI and Ex; and 3) to characterize GFL-responsive sensory fiber plasticity
      after SCI and Ex. Adult, female, Sprague-Dawley rats received a moderate,
      unilateral spinal cord contusion at C5. A subset of rats was exercised (SCI+Ex)
      on automated running wheels for 20min, 5days/week starting at 5days post-injury
      (dpi), continuing until 9 or 37dpi. Hargreaves' and von Frey testing was
      performed preoperatively and weekly post-SCI. Forty-two percent of rats in the
      unexercised group exhibited tactile allodynia of the forepaws while the other 58%
      retained normal sensation. The development of SCI-induced neuropathic pain
      correlated with a marked decrease in the levels of GDNF and artemin in the spinal
      cord and DRGs. Additionally, a dramatic increase in the density and the
      distribution throughout the dorsal horn of GFL-responsive afferents was observed
      in rats with SCI-induced allodynia. Importantly, in SCI rats that received Ex,
      the incidence of tactile allodynia decreased to 7% (1/17) and there was
      maintenance of GDNF and artemin at normal levels, with a normal distribution of
      GFL-responsive fibers. These data suggest that GFLs and/or their downstream
      effectors may be important modulators of pain fiber plasticity, representing
      effective targets for anti-allodynic therapeutics. Furthermore, we highlight the
      potent beneficial effects of acute exercise after SCI. 

PMID- 24560716
TI  - 1999-2014: 15 years of BCL10.

PMID- 24560715
TI  - Protection by vascular prostaglandin E2 signaling in hypoxic-ischemic
      encephalopathy.
AB  - Hypoxic-ischemic encephalopathy (HIE) in neonates is a leading cause of
      neurological impairment. Significant progress has been achieved investigating the
      pathologic contributions of excitotoxicity, oxidative stress, and
      neuroinflammation to cerebral injury in HIE. Less extensively investigated has
      been the contribution of vascular dysfunction, and whether modulation of cerebral
      perfusion may improve HIE outcome. Here, we investigated the function of the
      prostaglandin E2 (PGE2) EP4 receptor, a vasoactive Galphas-protein coupled
      receptor (GPCR), in rodent models of neonatal HIE. The function of PGE2 signaling
      through the EP4 receptor was investigated using pharmacological and conditional
      knockout genetic strategies in vivo in rodent models of HIE. Pharmacologic
      activation of the EP4 receptor with a selective agonist was significantly
      cerebroprotective both acutely and after 7days. Measurement of cerebral perfusion
      during and after hypoxia-ischemia demonstrated that EP4 receptor activation
      improved cerebral perfusion in both the contralateral and ipsilateral hypoxic
      ischemic hemispheres. To test whether vascular EP4 signaling exerted a critical
      function in HIE injury, cell specific conditional knockout mouse pups were
      generated in which endothelial EP4 receptor was selectively deleted postnatally.
      VE-Cadherin Cre-ER(T2);EP4(lox/lox) pups demonstrated significant increases in
      cerebral injury as compared to VE-Cadherin Cre-ER(T2);EP4(+/+) control
      littermates, indicating that endothelial EP4 signaling is protective in HIE. Our
      findings identify vascular PGE2 signaling through its EP4 receptor as protective
      in HIE. Given the pharmacologic accessibility of endothelial EP4 GPCRs, these
      data support further investigation into novel approaches to target cerebral
      perfusion in neonatal HIE. 

PMID- 24560718
TI  - Congenital vesicovaginal fistula with or without menouria: a literature review.
AB  - Congenital vesicovaginal fistula (CVVF) is a rare, complex female genital
      malformation that is difficult to diagnose, classify and treat. Symptoms include
      menouria, cyclical haematuria and urinary incontinence from birth. The aim of
      this review was to highlight the importance of correct diagnosis and treatment of
      this congenital anomaly. A comprehensive literature review was conducted to
      identify articles on CVVF with and without menouria. Forty-one articles were
      found, of which 31 described 37 original cases of congenital fistula (30 CVVF,
      six uterovesical fistula and one urethrovaginal fistula): 14 in girls and 23 in
      adults. The cases were classified according to clinical, diagnostic and
      therapeutic parameters in order to unify concepts and terms. Menouria occurred in
      21 of the 23 adults: 14 cases were CVVF, six cases were congenital uterovesical
      fistula, and one case was congenital urethrovaginal fistula in a young woman
      without congenital adrenal hyperplasia. Sixteen (53%) of the 30 patients with
      CVVF had urinary incontinence or hydrocolpometra, and 14 (47%) had menouria.
      There were associated anomalies in 91% of cases, 29 (48%) of which involved the
      urinary tract. Various diagnostic and therapeutic methods were used, and there
      was confusion surrounding the aetiopathogenesis in most cases. CVVF should be
      suspected in any girl with urinary incontinence, urinary tract infections from
      birth, vaginal swelling or hydrocolpometras, as well as in adults with menouria.
      Diagnosis should be based on physical examination and imaging (cystoscopy during
      menouria, ultrasound and magnetic resonance imaging). Surgical treatment should
      be based on correction of the vaginal defects (obstructive problem opening or
      vaginal reconstruction) and CVVF closure. The embryological origin of CVVF lies
      in the abnormal persistence of the urogenital sinus due to lack of formation and
      caudal growth of the urogenital wedge, combined with distinct degrees of agenesis
      or hypoplasia of the entire urogenital ridge or the mesonephric ducts (which
      affects development of the Mullerian ducts). 

PMID- 24560717
TI  - Common intrinsic connectivity states among posteromedial cortex subdivisions:
      Insights from analysis of temporal dynamics.
AB  - Perspectives of human brain functional connectivity continue to evolve. Static
      representations of functional interactions between brain regions are rapidly
      giving way to dynamic perspectives, which emphasize non-random temporal
      variations in intrinsic functional connectivity (iFC) patterns. Here, we bring
      this dynamic perspective to our understanding of iFC patterns for posteromedial
      cortex (PMC), a cortical hub known for its functional diversity. Previous work
      has consistently differentiated iFC patterns among PMC subregions, though assumed
      static iFC over time. Here, we assessed iFC as a function of time utilizing a
      sliding-window correlation approach, and applied hierarchical clustering to
      detect representative iFC states from the windowed iFC. Across subregions, five
      iFC states were detected over time. Although with differing frequencies, each
      subregion was associated with each of the states, suggesting that these iFC
      states are "common" to PMC subregions. Importantly, each subregion possessed a
      unique preferred state(s) and distinct transition patterns, explaining previously
      observed iFC differentiations. These results resonate with task-based fMRI
      studies suggesting that large-scale functional networks can be flexibly
      reconfigured in response to changing task-demands. Additionally, we used retest
      scans (~1week later) to demonstrate the reproducibility of the iFC states
      identified, and establish moderate to high test-retest reliability for various
      metrics used to quantify switching behaviors. We also demonstrate the ability of
      dynamic properties in the visual PMC subregion to index inter-individual
      differences in a measure of concept formation and mental flexibility. These
      findings suggest functional relevance of dynamic iFC and its potential utility in
      biomarker identification over time, as d-iFC methodologies are refined and
      mature.

PMID- 24560719
TI  - Health-related quality of life in older age and a risk of being a victim of
      domestic violence.
AB  - Violence against older people remains a taboo topic in Poland, and is still an
      under-recognized phenomenon. The aim of this study was to examine the risk of
      different types of domestic violence in older people in relation to their health
      related quality of life as measured by chronic conditions, functional
      limitations, psychological well-being, depressive symptoms and feelings of social
      isolation. A cross-sectional study using a standardized questionnaire in a simple
      random sample of 518 older citizens of Krakow was carried out. A multidimensional
      logistic regression of data showed that such factors as poor assessment of
      psychological health, number of chronic conditions, suffering from emotional and
      social loneliness and lack of social support in everyday life significantly
      increased the risk of being a victim of domestic violence in older citizens of
      Krakow. 

PMID- 24560720
TI  - SH wave propagation in magnetic-electric periodically layered plates.
AB  - In this paper, dispersive behavior and band structure of SH waves in magnetic
      electric (ME) periodically layered plate are investigated by the transfer matrix
      method. Two kinds of unit cell form, one is piezoelectric (PE)/piezomagnetic
      (PM)/PE, and the other is PM/PE/PM, are considered in detailed. A peculiar case
      of the generalized single-celled plate is first presented and then the multi
      celled periodical layered plates for discussion on the propagation behaviors and
      the band characteristics of SH waves, respectively. The effects on dispersive
      curves of four kinds of ME boundary conditions at the free surface of plates are
      discussed. Numerical examples for phase velocities or frequencies all show that
      the zero-order mode is non-dispersive both for single-celled and multi-celled
      periodically layered plates. The high modes of dispersive curves tend to the
      shear wave velocity of the slower sub-layer as frequencies increase both for
      these two structures. The frequency pass-band and frequency band gaps appear in
      multi-layered ME periodically layered plates. Electrical and magnetic boundary
      conditions, respectively, determine the dispersive curves for SH waves in the
      PE/PM/PE and PM/PE/PM periodically layered plates. 

PMID- 24560721
TI  - Endoplasmic reticulum stress in cerebral ischemia.
AB  - The endoplasmic reticulum (ER) stress is an essential step in the progression of
      brain ischemia/reperfusion (I/R) injury. It is possible that the timing of events
      for ER stress signaling regulation is important for the balance of life and death
      such that ER stress is initially protective, aiming to restore ER homeostasis,
      whereas prolonged periods of ER stress can be deleterious and damaging.
      Nevertheless, modulation of ER stress exerts a remarkable protective effect on
      the ischemic brain and offers the prospect of new stroke therapies. As ER stress
      is not devoid of deleterious side effects, a better understanding of the
      reciprocal interaction between the ER and the ischemic brain is essential to
      harness the full therapeutic potential of ischemic stroke. 

PMID- 24560722
TI  - Theoretical analysis of the determinants of lung oxygen diffusing capacity.
AB  - The process of pulmonary oxygen uptake is analyzed to obtain an explicit equation
      for lung oxygen diffusing capacity in terms of hematocrit and pulmonary capillary
      diameter. An axisymmetric model with discrete cylindrical erythrocytes is used to
      represent radial diffusion of oxygen from alveoli through the alveolar-capillary
      membrane into pulmonary capillaries, through the plasma, and into erythrocytes.
      Analysis of unsteady diffusion due to the passage of the erythrocytes shows that
      transport of oxygen through the alveolar-capillary membrane occurs mainly in the
      regions adjacent to erythrocytes, and that oxygen transport through regions
      adjacent to plasma gaps can be neglected. The model leads to an explicit formula
      for diffusing capacity as a function of geometric and oxygen transport
      parameters. For normal hematocrit and a capillary diameter of 6.75 MUm, the
      predicted diffusing capacity is 102 ml O2 min-1 mmHg-1. This value is 30-40%
      lower than values estimated previously by the morphometric method, which
      considers the total membrane area and the specific uptake rate of erythrocytes.
      Diffusing capacity is shown to increase with increasing hematocrit and decrease
      with increasing capillary diameter and increasing thickness of the membrane.
      Simulations of pulmonary oxygen uptake in humans under conditions of exercise or
      hypoxia based show closer agreement with experimental data than previous models,
      but still overestimate oxygen uptake. The remaining discrepancy may reflect
      effects of heterogeneity of perfusion and ventilation in the lung.

PMID- 24560723
TI  - Competition and allelopathy with resource storage: two resources.
AB  - Allelopathy is added to a familiar mathematical model of competition between two
      species for two essential resources in a chemostat environment. Both species
      store the resources, and each produces a toxin that induces mortality in the
      other species. The corresponding model without toxins displays outcomes of
      competitive exclusion independent of initial conditions, competitive exclusion
      that depends on initial conditions (bistability), and globally stable
      coexistence, depending on tradeoffs between competitors in growth requirements
      and consumption of the resources. Introducing toxins that act only between, and
      not within species, can destabilize coexistence leading to bistability or other
      multiple attractors. Invasibility of the missing species into a resident's
      semitrivial equilibrium is related to competitive outcomes. Mutual invasibility
      is necessary and sufficient for a globally stable coexistence equilibrium, but is
      not necessary for coexistence at a locally stable equilibrium. Invasibility of
      one semitrivial equilibrium but not the other is necessary but not sufficient for
      competitive exclusion independent of initial conditions. Mutual non-invasibility
      is necessary but not sufficient for bistability. Numerical analysis suggests that
      when competitors display bistability in the absence of toxin production,
      increases in the overall magnitude of resource supply cause bistability to arise
      over a larger range of supply ratios between the two resources. When competitors
      display coexistence in the absence of toxin production, increases in overall
      resource supply destabilize coexistence and produce bistability or other
      configurations of multiple attractors over large ranges of supply ratios. The
      emergence of multiple attractors at high resource supplies suggests that blooms
      of harmful algae producing allelopathic toxins could be difficult to predict
      under such rich conditions. 

PMID- 24560724
TI  - The split genes of Nanoarchaeum equitans have not originated in its lineage and
      have been merged in another Nanoarchaeota: a reply to Podar et al.
AB  - I reply to the suggestion of Podar et al. (2013) that the split genes of
      Nanoarchaeun equitans are a derived character, showing that their analysis is
      mistaken. In particular, I show that the split genes both proteins and tRNAs have
      not been split in N. equitans and have been on the contrary merged in the
      nanoarchaeon sequenced recently by Podar et al. (2013). This implies that the
      main argument of Podar et al. (2013) that there should be: "a unique propensity
      for splitting in the Nanoarchaeota that is most dramatically manifested in the
      Nanoarchaeum equitans lineage" is false. On the other hand, the analysis seems to
      favor the hypothesis that the split genes are an ancestral character. This would
      strengthen to greater extent a model for the origin of the tRNA molecule. 

PMID- 24560725
TI  - A model for computing genes governing marital dissolution through sentimental
      dynamics.
AB  - Adverse sentimental relationships that cause marital dissolution may involve a
      genetic component composed of genes from a couple, which interact with cultural,
      sociological, psychological and economic factors. However, the identification of
      these genes is very challenging. Here, we address this challenge by developing a
      computational model that can identify specific genes that impact on sentimental
      relationships of couples. The model was derived by implementing the second law of
      thermodynamics that quantifies sentimental relationships within a dynamic gene
      identification framework, called systems mapping. The model is equipped with a
      capacity to characterize and test the pattern of how genes from a couple interact
      with each other to determine the dynamic behavior of their marital relationships.
      The testing procedure is based on comparing genotypic differences in mathematical
      parameters of sentimental dynamics described by a group of ordinary differential
      equations (ODE). The model allows the test of individual parameters or a
      combination of parameters, addressing specific details related to martial
      relationships. The model may find its implications for designing an optimal
      effort policy and therapy to maintain a harmonic family in light of genetic
      blueprints of individual couples.

PMID- 24560726
TI  - Determination of asymmetric Nalpha-acetyldimethylarginine in humans: a phase II
      metabolite of asymmetric dimethylarginine.
AB  - Asymmetric dimethylarginine (ADMA) is produced by protein methylation, a common
      mechanism of posttranslational protein modification. Elevated levels of ADMA lead
      to impaired endothelial nitric oxide production and subsequently to a range of
      cardiovascular and other diseases related to decreased nitric oxide production.
      Knowledge of the elimination pathways of ADMA and the possibility of influencing
      them is therefore of major clinical interest. One of these pathways is the N
      acetylation and subsequent renal elimination of ADMA in the form of asymmetric
      Nalpha-acetyldimethylarginine (Ac-ADMA). In this work, we describe the first
      method to quantitatively determine Ac-ADMA in human plasma and urine. Ac-ADMA was
      separated by HPLC on a porous graphitic carbon column and selectively analyzed by
      tandem mass spectrometry. Ac-ADMA and the internal standard D7-Ac-ADMA were
      synthesized in-house. Precision and accuracy of the method were better than 5% in
      plasma and urine quality control samples. First results obtained with this method
      in samples of healthy volunteers showed plasma levels of 0.643+/-0.454 nmol/L and
      urine levels of 152.7+/-76.7 nmol/L or 13.0+/-8.9 nmol/mmol creatinine. The
      method is a suitable tool for investigating this currently mostly neglected ADMA
      elimination pathway.

PMID- 24560727
TI  - A high-throughput protocol for message RNA quantification using RNA dot-blots.
AB  - This study develops a method to rapidly measure the relative abundance of mRNA in
      total RNA samples using a dot-blotting technique and biotin-labeled detection
      probes that recognize the polyadenylate tail on mRNA. We demonstrate the
      effectiveness of this technique by determining the relative total amounts of mRNA
      in three tissues of turtles (Trachemys scripta elegans) exposed to normoxic
      versus anoxic conditions. The data emphasize the usefulness of the method for the
      simple and rapid analysis of relative total mRNA levels for a variety of
      comparison purposes. 

PMID- 24560728
TI  - Cloning and characterization of neoplasia-related genes in flat oyster Ostrea
      edulis.
AB  - Bonamiosis and disseminated neoplasia (DN) are the most important diseases
      affecting cultured flat oysters Ostrea edulis in Galicia (NW Spain). Previous
      research using suppresive substraction hybridisation that had been performed
      addressing the molecular basis of DN as well as the induction and development of
      the disease in oysters, yielded the whole open reading frame of nine genes: XBP
      1, RACK, NDPk, C1qTNF, RPA3, SAP18, p23, ubiquitin and ferritin. These nine genes
      were characterized in this study. The phylogenetic relationships for each gene
      were studied using minimum-evolution methods. Quantitative-PCR assays were also
      developed to analyse the modulation of the expression of these genes by
      bonamiosis and disseminated neoplasia. Gene expression profiles were studied in
      haemolymph cells and in various organs (gill, gonad, mantle and digestive gland)
      of oysters affected by bonamiosis, disseminated neoplasia, both diseases and in
      non-affected oysters (control). The expression of XBP-1, NDPk, RPA3, SAP18 and
      ferritin increased in haemolymph cells of oysters with heavy bonamiosis. The
      expression of C1qTNF; SAP18 and p23 increased in haemolymph cells of oysters with
      DN. The expression of XBP-1, RACK, NDPk, RPA3 and p23 significantly increased in
      haemolymph cells of oysters affected by both diseases. There were changes in the
      expression of a number of genes in different organs depeding on disease stage:
      RACK expression increased in gills of oysters with bonamiosis, XBP-1 increased in
      mantle and digestive organs of oysters with light DN and RPA3 expression
      increased in gonads of oysters with heavy bonamiosis and heavy neoplasia. 

PMID- 24560729
TI  - Evolution, molecular epidemiology and perspectives on the research of taeniid
      parasites with special emphasis on Taenia solium.
AB  - Human cysticercosis is known since old historical times in Greece and China;
      however, human infections by tapeworms have accompanied human beings for more
      that hundred thousand years. The disease is tightly bound to poverty and lack of
      hygiene, and has been eradicated in developed countries, but continues being a
      public health problem in developing countries of Latin-American, Sub-Saharan
      Africa and Asia, and is also remerging in a number of non endemic countries. It
      is considered a neglected disease. Here we revise a number of key scientific
      contributions on taeniid biology that open new avenues for more effective
      approaches to the control of cysticercosis. The evolution of flatworms and class
      Cestoda is analyzed, with special emphasis on the emergence of taeniid parasites
      and the colonization of the human species by tapeworms. The complex molecular
      host-parasite interplay in this relationship as result of co-evolution between
      two distantly related organisms. The relevant host and parasite's factors, in the
      prospect of identifying species-specific molecular markers useful in
      epidemiological studies carried out in endemic countries. The new possibilities
      arising with the characterization of the genomes for several species of
      tapeworms, including a deeper understanding of these organisms, as well as
      improved tools for diagnosis, vaccination and drug treatment. The need to revise
      the current control and management strategies for this tropical neglected
      disease. 

PMID- 24560732
TI  - [H-type tracheoesophageal fistula in neonates: different therapeutic approaches].

PMID- 24560731
TI  - [Universal cytomegalovirus infection screening in premature newborns less than
      1500 g].
AB  - INTRODUCTION: Cytomegalovirus (CMV) infection is endemic, and children who attend
      day care are the most important source of infection. OBJECTIVE: To establish
      recommendations based on the medical evidence on the vertical transmission of
      cytomegalovirus in preterm infants weighing less than 1500g at birth. BACKGROUND:
      Infection in pregnant women may be primary or secondary. Although there is fetal
      infection, 85% of newborn infants are asymptomatic. Symptoms of infection include
      low birth weight, hepatosplenomegaly, thrombocytopenia, microcephaly and
      neurological disorders. The prognosis of symptomatic children is very poor, with
      high mortality and neurological disorders. The virus can be reactivated during
      breast feeding, and early infection is possible through breast milk, probably
      with little impact in term infants, although the long-term neurological outcome
      worsens in preterm infants. The diagnostic method of choice is the identification
      of CMV in urine; the determination in the first two weeks of life suggests
      congenital infection; later it can be acquired at birth or through breast milk or
      contaminated blood transfusion. CONCLUSION AND RECOMMENDATION: Determine viral
      DNA at 4-6 weeks of life by protease chain reaction. If it is positive,
      monitoring of samples from the first days of life and breast milk are mandatory.
      This should allow the newborn to be classified into three states: "Without CMV
      infection", "Congenital CMV infection", "Acquired CMV infection".

PMID- 24560730
TI  - [Usefulness of bedside ultrasound compared to capnography and X-ray for tracheal
      intubation].
AB  - OBJECTIVES: The aim of this study was to assess the usefulness of bedside
      ultrasound compared to capnography and X-ray for endotracheal intubation in
      children and newborns. MATERIALS AND METHODS: Hemodynamically stable children
      intubated in pedriatric and neonatal intensive care unit were included.
      Endotracheal tube insertion was checked after every intubation attempt by
      tracheal ultrasound and capnography simultaneously. The endotracheal tube
      insertion depth was then checked by assesment of lung sliding by thoracic
      ultrasound. Thereafter, Chest X-ray was performed and interpreted as usual. Time
      to perform each technique was recorded. RESULTS: The study included 31
      intubations in 26 patients (15 in PICU and 16 in NICU). There were no
      statistically significant differences between tracheal ultrasound and capnography
      or between thoracic ultrasound and x-ray in identifying the correct endotracheal
      intubation and assessment of endotracheal tube insertion depth, respectively.
      Sensibility and specificity of ultrasound compared to capnography was 92% and
      100%, and 100% and 75% compared to X-ray. Ultrasound was significantly slower
      compared to capnography [12 (4-16) vs 6 (3-12) seconds; P<.001] and significantly
      quicker compared to X-ray [0.22 (0.17-0.40) vs. 20 (17-25) minutes, P<.001].
      CONCLUSIONS: Ultrasound appears to be as effective as capnography, although
      slower, for identifying endotracheal intubation. Ultrasound may be useful in
      clinical situations, such as cardiopulmonary resuscitation where capnography is
      less reliable. Ultrasound is as effective and quicker than X-ray for assessment
      of endotracheal tube insertion depth, and it may contribute to decrease the
      routine use of X-ray after tracheal intubation.

PMID- 24560733
TI  - Body mass index and myocardium at risk in patients with acute coronary syndrome.
AB  - BACKGROUND AND OBJECTIVES: Whilst traditional studies have shown that obese
      individuals are at a higher risk of cardiovascular events compared to lean
      subjects, recent studies in patients with acute myocardial infarction (AMI) have
      suggested that obesity may exert protective effects (the "obesity paradox"). We
      sought to assess the relationship between body mass index (BMI) and the BARI
      score (BARIsc), a validated tool used to assess myocardium at risk, in patients
      with acute coronary syndrome. PATIENTS AND METHODS: Participants were 116
      consecutive patients (mean age, 60.6 years; 97 men) with AMI (68 ST elevated
      myocardial infarction, STEMI; 48 non-ST elevated myocardial infarction, NSTEMI).
      Demographics, BMI, risk factors, biochemistry data, left ventricular function,
      angiographic data and the BARIsc were assessed in every patient. RESULTS:
      Multiple linear regression analyses showed that BMI significantly correlated with
      BARIsc; beta=.23, p<0.02. This was found only in the overweight/obese patients,
      beta=.27, p<0.01, but not in patients with normal BMIs, beta=0.08, p=0.71.
      CONCLUSIONS: An increased body weight is associated with an increased area of
      myocardium at risk in patients with ACS.

PMID- 24560734
TI  - Takayasu's arteritis associated with Crohn's disease.

PMID- 24560735
TI  - [Satisfaction surveys: an opportunity to improve].

PMID- 24560736
TI  - [Acute coronary syndrome associated with nebulized salbutamol].

PMID- 24560737
TI  - Benzenesulfonamide bearing 1,2,4-triazole scaffolds as potent inhibitors of tumor
      associated carbonic anhydrase isoforms hCA IX and hCA XII.
AB  - Three series of novel heterocyclic compounds (3a-3g, 4a-4g and 5a-5g) containing
      benzenesulfonamide moiety and incorporating a 1,2,4-triazole ring, have been
      synthesized and investigated as inhibitors against four isomers of the alpha
      class carbonic anhydrases (CAs, EC 4.2.1.1), comprising hCAs I and II (cytosolic,
      ubiquitous isozymes) and hCAs IX and XII (transmembrane, tumor associated
      isozymes). Against the human isozymes hCA I and II, compounds of two series (3a
      3g and 4a-4g) showed Ki values in the range of 84-868 nM and 5.6-390 nM,
      respectively whereas compounds of series 5a-5g were found to be poor inhibitors
      (Ki values exceeding 10,000 nM in some cases). Against hCA IX and XII, all the
      tested compounds exhibited excellent to moderate inhibitory potential with Ki
      values in the range of 2.8-431 nM and 1.3-63 nM, respectively. Compounds 3d, 3f
      and 4f exhibited excellent inhibitory potential against all of the four isozymes
      hCA I, II, IX and XII, even better than the standard drug acetazolamide (AZA)
      whereas compound of the series 5a-5g were comparatively less potent but more
      selective towards hCA IX and XII.

PMID- 24560738
TI  - Alkynyl-coumarinyl ethers as MAO-B inhibitors.
AB  - In this study, alkynyl-coumarinyl ethers were developed as inhibitors of human
      monoamine oxidase B (MAO-B). A series of 31 new, ether-connected coumarin
      derivatives was synthesized via hydroxycoumarins, whose phenolic group at
      position 6, 7 or 8 was converted by means of the Mitsunobu reaction. The majority
      of the final products were produced from primary alcohols with a terminal alkyne
      group. The inhibitors were optimized with respect to the structure of the
      alkynyloxy chain and its position at the fused benzene ring as well as the
      residue at position 3 of the pyran-2H-one part. A hex-5-ynyloxy chain at position
      7 was found to be particular advantageous. Among the 7-hex-5-ynyloxy-coumarins,
      the 3-methoxycarbonyl derivative 36 was characterized as a dual-acting inhibitor
      with IC50 values of less than 10 nM towards MAO-A and MAO-B, and the 3-(4
      methoxy)phenyl derivative 44 was shown to combine strong anti-MAO-B potency
      (IC50=3.0 nM) and selectivity for MAO-B over MAO-A (selectivity >3400-fold).

PMID- 24560739
TI  - Design, synthesis and evaluation of N-substituted saccharin derivatives as
      selective inhibitors of tumor-associated carbonic anhydrase XII.
AB  - A series of N-alkylated saccharin derivatives were synthesized and tested for the
      inhibition of four different isoforms of human carbonic anhydrase (CA, EC 4.
      2.1.1): the transmembrane tumor-associated CA IX and XII, and the cytosolic CA I
      and II. Most of the reported derivatives inhibited CA XII in the nanomolar/low
      micromolar range, hCA IX with KIs ranging between 11 and 390 nM, whereas they
      were inactive against both CA I (KIs >50 MUM) and II (K(I)s ranging between 39.1
      nM and 50 MUM). Since CA I and II are off-targets of antitumor carbonic anhydrase
      inhibitors (CAIs), the obtained results represent an encouraging achievement for
      the development of new anticancer candidates without the common side effects of
      non-selective CAIs. Moreover, the lack of an explicit zinc binding function on
      these inhibitors opens the way towards the exploration of novel mechanisms of
      inhibition that could explain the high selectivity of these compounds for the
      inhibition of the transmembrane, tumor-associated isoforms over the cytosolic
      ones.

PMID- 24560740
TI  - Development, implementation and evaluation of a disaster training programme for
      nurses: a Switching Replications randomized controlled trial.
AB  - BACKGROUND: Training efforts in disaster education need to provide updated
      knowledge, skills and expertise to nurses through evidence-based interventions.
      AIM: The purpose of the study was the development, implementation and evaluation
      of an educational programme for nurses regarding the provision of health care
      during disasters. METHODS: A randomized controlled trial using Switching
      Replications design was conducted for the evaluation of the programme. 207
      hospital-based nurses were randomly assigned into intervention (n = 112) and
      original control (n = 95) groups. Changes between groups and over time were
      measured by questionnaire and used as the outcome measure to demonstrate
      effectiveness of the training intervention. RESULTS: The intervention improved
      nurses' knowledge and self-confidence levels while no significant changes were
      detected in behavioral intentions. A significant increase in the mean knowledge
      score was observed in both groups in times 2 and 3 compared to time 1 [pre-test:
      6.43 (2.8); post-test: 16.49 (1.7); follow-up test: 13.5 (2.8)], (P < 0.002).
      Changes in knowledge between intervention and control group were significantly
      different (P < 0.001) with a large effect size (eta-squared = 0.8). CONCLUSIONS:
      The training programme was feasible and effective in improving nurses' knowledge
      concerning disaster response.

PMID- 24560741
TI  - Hypocapnia leads to enhanced expression of pluripotency and meso-endodermal
      differentiation genes in mouse embryonic stem cells.
AB  - The efficient utilization of embryonic stem cells for applications like cell
      based therapy, transplantation and drug discovery largely depends upon the
      culturing conditions of these cells. In this report, we have analyzed gene,
      protein expression and morphological changes of embryonic stem cells when
      subjected to lowered CO2 levels i.e. hypocapnia. We studied the quantitative
      expression of pluripotent genes, Oct3/4, Nanog and Sox2 and genes involved in the
      differentiation to the three lineages, under varying CO2 levels. Enhanced
      expression of these genes was seen at cultures maintained at 1.5% CO2 as compared
      to those maintained at 5% CO2. The cells exposed to hypocapnic conditions when
      subjected to immunocytochemical analysis stained positive for Oct-3/4, Nanog and
      Sox2 transcription factors. Flow cytometry and western blot further showed that
      the pluripotent proteins in the 1.5% CO2 maintained cultures have higher levels
      of expression as compared to the ES cells at 5% CO2. In addition, there was
      enhanced differentiation particularly towards the mesodermal and endodermal
      lineages at cultures maintained and differentiated at 1.5% CO2 at all the time
      periods analyzed i.e. day 10 (5+5d), 12 (5+7d) and day 15 (5+10d). These results,
      which we feel are the first of their kind, indicate that lowered CO2 levels seem
      to be preferred for the maintenance of pluripotency and the subsequent
      differentiation. 

PMID- 24560742
TI  - Regulatory mechanisms of Hertwig's epithelial root sheath formation and anomaly
      correlated with root length.
AB  - Teeth are composed of two domains, the enamel-covered crown and cementum-covered
      root. The mechanism for determining the transition from crown to root is
      important for understanding root anomaly diseases. Hertwig's epithelial root
      sheath (HERS) is derived from the dental epithelium and is known to drive the
      growth of root dentin and periodontal tissue. Some clinical cases of hypoplastic
      tooth root are caused by the cessation of HERS development. Understanding the
      mechanisms of HERS development will contribute to the study of the disease and
      dental regenerative medicine. However, the developmental biology of tooth root
      formation has not been fully studied, particularly regarding HERS formation.
      Here, we describe the mechanisms of HERS formation on the basis of analysis of
      cell dynamics using imaging and summarize how the growth factor and its receptor
      regulate cell behavior of the dental epithelium. 

PMID- 24560743
TI  - Generation of transgene-free mouse induced pluripotent stem cells using an
      excisable lentiviral system.
AB  - One goal of research using induced pluripotent stem cell (iPSC) is to generate
      patient-specific cells which can be used to obtain multiple types of
      differentiated cells as disease models. Minimally or non-integrating methods to
      deliver the reprogramming genes are considered to be the best but they may be
      inefficient. Lentiviral delivery is currently among the most efficient methods
      but it integrates transgenes into the genome, which may affect the behavior of
      the iPSC if integration occurs into an important locus. Here we designed a
      polycistronic lentiviral construct containing four pluripotency genes with an
      EGFP selection marker. The cassette was excisable with the Cre-loxP system making
      possible the removal of the integrated transgenes from the genome. Mouse
      embryonic fibroblasts were reprogrammed using this viral system, rapidly
      resulting in large number of iPSC colonies. Based on the lowest EGFP expression
      level, one parental line was chosen for excision. Introduction of the Cre
      recombinase resulted in transgene-free iPSC subclones. The effect of the
      transgenes was assessed by comparing the parental iPSC with two of its transgene
      free subclones. Both excised and non-excised iPSCs expressed standard
      pluripotency markers. The subclones obtained after Cre recombination were capable
      of differentiation in vitro, in contrast to the parental, non-excised cells and
      formed germ-line competent chimeras in vivo. 

PMID- 24560744
TI  - A morphological and functional comparison of proximal tubule cell lines
      established from human urine and kidney tissue.
AB  - Promising renal replacement therapies include the development of a bioartificial
      kidney using functional human kidney cell models. In this study, human
      conditionally immortalized proximal tubular epithelial cell (ciPTEC) lines
      originating from kidney tissue (ciPTEC-T1 and ciPTEC-T2) were compared to ciPTEC
      previously isolated from urine (ciPTEC-U). Subclones of all ciPTEC isolates
      formed tight cell layers on Transwell inserts as determined by transepithelial
      resistance, inulin diffusion, E-cadherin expression and immunocytochemisty.
      Extracellular matrix genes collagen I and -IV alpha1 were highly present in both
      kidney tissue derived matured cell lines (p<0.001) compared to matured ciPTEC-U,
      whereas matured ciPTEC-U showed a more pronounced fibronectin I and laminin 5
      gene expression (p<0.01 and p<0.05, respectively). Expression of the influx
      carrier Organic Cation Transporter 2 (OCT-2), and the efflux pumps P-glycoprotein
      (P-gp), Multidrug Resistance Protein 4 (MRP4) and Breast Cancer Resistance
      Protein (BCRP) were confirmed in the three cell lines using real-time PCR and
      Western blotting. The activities of OCT-2 and P-gp were sensitive to specific
      inhibition in all models (p<0.001). The highest activity of MRP4 and BCRP was
      demonstrated in ciPTEC-U (p<0.05). Finally, active albumin reabsorption was
      highest in ciPTEC-T2 (p<0.001), while Na(+)-dependent phosphate reabsorption was
      most abundant in ciPTEC-U (p<0.01). In conclusion, ciPTEC established from human
      urine or kidney tissue display comparable functional PTEC specific transporters
      and physiological characteristics, providing ideal human tools for bioartificial
      kidney development. 

PMID- 24560745
TI  - Furin processing dictates ectodomain shedding of human FAT1 cadherin.
AB  - Fat1 is a single pass transmembrane protein and the largest member of the
      cadherin superfamily. Mouse knockout models and in vitro studies have suggested
      that Fat1 influences cell polarity and motility. Fat1 is also an upstream
      regulator of the Hippo pathway, at least in lower vertebrates, and hence may play
      a role in growth control. In previous work we have established that FAT1 cadherin
      is initially cleaved by proprotein convertases to form a noncovalently linked
      heterodimer prior to expression on the cell surface. Such processing was not a
      requirement for cell surface expression, since melanoma cells expressed both
      unprocessed FAT1 and the heterodimer on the cell surface. Here we further
      establish that the site 1 (S1) cleavage step to promote FAT1 heterodimerisation
      is catalysed by furin and we identify the cleavage site utilised. For a number of
      other transmembrane receptors that undergo heterodimerisation the S1 processing
      step is thought to occur constitutively but the functional significance of
      heterodimerisation has been controversial. It has also been generally unclear as
      to the significance of receptor heterodimerisation with respect to subsequent
      post-translational proteolysis that often occurs in transmembrane proteins.
      Exploiting the partial deficiency of FAT1 processing in melanoma cells together
      with furin-deficient LoVo cells, we manipulated furin expression to demonstrate
      that only the heterodimer form of FAT1 is subject to cleavage and subsequent
      release of the extracellular domain. This work establishes S1-processing as a
      clear functional prerequisite for ectodomain shedding of FAT1 with general
      implications for the shedding of other transmembrane receptors. 

PMID- 24560746
TI  - Scimitar syndrome associated with gallbladder duplication.
AB  - Scimitar syndrome is a rare congenital anomaly associated with the venous
      drainage of the lung to the inferior vena cava through a systemic vein. Chest
      radiography of an asymptomatic patient, aged 36, showed a linear opacity
      extending from the pulmonary hilum to the diaphragm, on the right chest (Scimitar
      sign). Computerized tomography of the thorax exposed that the cause of that image
      was Scimitar vein. Abdominal ultrasonography revealed duplication in the
      gallbladder. The literature holds no reports of an association between Scimitar
      syndrome and gallbladder duplication. Secondary gastrointestinal malformations
      can also be found in patients suffering from this syndrome. 

PMID- 24560747
TI  - Computed tomography and magnetic resonance imaging findings of acquired
      dacryocystoceles.
AB  - In this study, radiological findings of acquired dacryocystocele are presented. A
      total of 13 dacryocystoceles including bilateral in two of the patients, in four
      patients on the left and in five patients on the right, were determined. Six of
      the patients had dacryocystocele infection. Average density of the non-infected
      dacryocystoceles was 11.8+/-7.8 Haunsfield units (HU), while the median density
      value of infected ones was 35.0 HU. There was expansion on unilateral
      nasolacrimal duct in four patients. Acquired dacryocystoceles are rare masses in
      medial canthal area, and their radiological imaging findings may vary based on
      etiological factors and presence of infections. 

PMID- 24560748
TI  - Depiction of celiac ganglia on positron emission tomography and computed
      tomography in patients with lung cancer.
AB  - OBJECTIVE: To differentiate imaging characteristics of celiac ganglia from
      metastatic lesion on positron emission tomography-computed tomography (PET-CT) in
      patients with lung cancer and correlate these findings to postmortem
      multidetector row computed tomography (MDCT). METHODS: One hundred twenty-nine
      patients were included. Imaging characteristics and fluorodeoxyglucose (FDG)
      avidity of the celiac ganglia were recorded. Postmortem MDCT of 20 subjects were
      reviewed. RESULTS: Celiac ganglia were identified unilaterally in 127 and
      bilaterally in 108 patients without abnormal FDG uptake. Postmortem images showed
      celiac ganglia in all cases with no significant difference compared to our
      patients. CONCLUSIONS: Familiarity with CT characteristics and FDG-avidity of
      celiac ganglia enable us to distinguish them from metastatic lesions in their
      vicinity.

PMID- 24560749
TI  - Management of patients with incidental findings in imaging tests: a large
      prospective single-center study.
AB  - We prospectively followed up patients with an incidental finding detected in an
      image test to assess the additional interventions carried out and the clinical
      implications of the incidental findings detected. Out of 474 patients with an
      incidental finding, 63 (13.3%) were further evaluated, and of these patients, 25
      (39.7%) had clinical implications. Patients who had an X-ray (24/76, 31.6%), with
      a preoperative examination (19/77 24.7%), and with an incidental finding in the
      thoracic cavity (34/117, 29.1%) or in the head/neck (6/28, 21.4%) were more
      likely to have additional evaluations. 

PMID- 24560750
TI  - Review of international patterns of practice for the treatment of painful bone
      metastases with palliative radiotherapy from 1993 to 2013.
AB  - BACKGROUND AND PURPOSE: Numerous randomized controlled trials and meta-analyses
      have affirmed that single and multiple fractions of radiotherapy provide equally
      efficacious outcomes in the palliation of painful, uncomplicated bone metastases
      (UBM). We aim to determine geographic, temporal and ancillary factors that
      influence the global patterns of practice in this setting. MATERIALS AND METHODS:
      A literature search was conducted on Ovid MEDLINE and EMBASE. Studies were
      included if they disclosed prescription patterns of single fraction radiotherapy,
      either through hypothetical cases or actual patient data. Weighted analysis of
      variance was conducted for binary predictors while weighted linear regression
      analysis was performed for continuous parameters. RESULTS: Nine hypothetical case
      studies and thirteen actual patterns of practice articles were included from 301
      search results. Radiation oncologists prescribed dose fractionations ranging from
      3Gy*1 to 2Gy*30, with a median of 3Gy*10, for the palliation of UBM. Actual data
      demonstrated a weak, non-significant, negative linear relationship between the
      use of single fraction radiotherapy and the year of treatment. Geographical
      location of treatment was a key predictor of prescription patterns. CONCLUSION:
      In the last twenty years, there was an overall global reluctance to practice
      evidence-based medicine by employing single fractions for UBM.

PMID- 24560751
TI  - The Quadrella: a novel approach to analyzing optimal outcomes after permanent
      seed prostate brachytherapy.
AB  - BACKGROUND AND PURPOSE: To study a four-point combined analysis (Quadrella) of
      optimal outcome among patients treated with exclusive permanent seed prostate
      brachytherapy (PB), as defined by the likelihood of achieving disease control and
      preserving normal urinary, gastro-intestinal (GI) and sexual function. MATERIALS
      AND METHODS: 384 patients with localized prostate cancer underwent PB at our
      institution with (125)I at a dose level of 144Gy. Subjects with erectile
      dysfunction who did not respond to medication were excluded. 281 patients with
      minimum 3-year follow-up were evaluated. Patients with concurrent biochemical
      progression-free survival (bPFS), absent urinary and GI toxicities (grade 0
      toxicities according to CTCAE v 3.0) and preserved sexual potency (with our
      without medication) were classified as the Quadrella group. RESULTS: Among the
      281 patients analyzed, the Quadrella was achieved in 49.1%, 48.0%, 50.4%, 41.7%
      and 65.2% in years 3-7, respectively. bPFS rates were 82.6-96.1%, corresponding
      potency rates were 63.6-82.3%, and normal urinary and GI function rates were 64.8
      82.6% and 95-100%, respectively. By multivariate analysis, significant predictors
      of Quadrella were age (p=0.015), baseline IPSS (p=0.03) and time since PB
      (p=0.02). CONCLUSION: Urinary and sexual toxicity remained the most common
      reasons for excluding patients from a perfect outcome (Quadrella), defined by
      strict criteria. This analysis can be useful for subsequent comparison between
      treatment modalities.

PMID- 24560752
TI  - Neutron therapy and increased late complication rates.

PMID- 24560753
TI  - Modeling positioning uncertainties of prostate cancer external beam radiation
      therapy using pre-treatment data.
AB  - PURPOSE: To investigate the influence of treatment plan data and image guidance
      (IG) on positioning uncertainty during prostate cancer (PCa) radiotherapy (RT).
      METHODS: Body mass index (BMI), planning target volume (PTV), bladder volume
      (BV), and rectal cross section area (RCS) were collected for 267 consecutive PCa
      patients undergoing daily IGRT. Radiographic isocenter corrections to intra
      prostatic fiducials for 12,490 treatment fractions were used to derive random
      (RE) and systematic (SE) inter-fraction uncertainties for the cardinal axes.
      These data were used to simulate RE and SE for weekly IG and Action Level (AL)-IG
      treatment protocols. RESULTS: SE and RE were 2-5 and 3-4mm in the cardinal axes,
      respectively, during simulation of no IG. Without IG, positive correlations
      (p<0.01) were noted for (1) anterior-posterior RE vs. RCS and BV and (2) cranio
      caudal RE vs. RCS, BV and BMI. The RE increase was 3mm for the highest quartile
      of RCS, BV and BMI. Daily IGRT eliminated this relationship. 3D IG corrections of
      1cm or more occured in 27% of treatment fractions and in 97% of patients.
      CONCLUSION: PCa patients with elevated pre-treatment BV, RCS and BMI have
      increased inter-fractionation positioning uncertainty and appear the primary
      candidates for daily IGRT.

PMID- 24560754
TI  - Non-invasive anesthesia for children undergoing proton radiation therapy.
AB  - BACKGROUND: Proton therapy is a newer modality of radiotherapy during which
      anesthesiologists face specific challenges related to the setup and duration of
      treatment sessions. PURPOSE: Describe our anesthesia practice for children
      treated in a standalone proton therapy center, and report on complications
      encountered during anesthesia. MATERIALS AND METHODS: A retrospective review of
      anesthetic records for patients ?18years of age treated with proton therapy at
      our institution between January 2006 and April 2013 was performed. RESULTS: A
      total of 9328 anesthetics were administered to 340 children with a median age of
      3.6years (range, 0.4-14.2). The median daily anesthesia time was 47min (range, 15
      79). The average time between start of anesthesia to the start of radiotherapy
      was 7.2min (range, 1-83min). All patients received Total Intravenous Anesthesia
      (TIVA) with spontaneous ventilation, with 96.7% receiving supplemental oxygen by
      non-invasive methods. None required daily endotracheal intubation. Two episodes
      of bradycardia, and one episode each of; seizure, laryngospasm and bronchospasm
      were identified for a cumulative incidence of 0.05%. CONCLUSIONS: In this large
      series of children undergoing proton therapy at a freestanding center, TIVA
      without daily endotracheal intubation provided a safe, efficient, and less
      invasive option of anesthetic care.

PMID- 24560755
TI  - Update report of nasopharyngeal carcinoma treated with reduced-volume intensity
      modulated radiation therapy and hypothesis of the optimal margin.
AB  - BACKGROUND AND PURPOSE: To establish the minimally required margins in different
      directions measured from GTV in the definitive treatment of nasopharyngeal
      carcinoma (NPC) using IMRT based on the 5-year results. METHODS AND MATERIALS:
      Between November 2003 and May 2007, 414 patients with non-metastatic NPC were
      treated with IMRT according to our institutional protocol. Treatment outcomes at
      5 years were analyzed. Distances from GTV-T to CTV2 (i.e., CTV 59.4 Gy) in 6
      directions (anterior, posterior, superior, inferior, and bilateral) were measured
      and analyzed. RESULTS: The 5-year estimated overall survival (OS), disease free
      survival (DFS), local control (LC) were 80%, 77% and 95%, respectively. For the
      margins measured from GTV-T to CTV2, margins used with T4 disease were
      significantly and uniformly smaller than the whole group in all the 6 directions
      (P=0.000, 0.000, 0.000, 0.000 and 0.046, respectively). However, no increase of
      local recurrence was associated to this limited margins used. CONCLUSIONS: Our 5
      years' experience showed a very high LC rate. The strategy we used for CTV
      delineation was safe and reliable. Determined CTV through GTV expansion to a
      minimally required margin, using GTV+margin (used in our T4 patients)+the whole
      nasopharyngeal mucosa, especially for the patients with early T disease, might be
      feasible.

PMID- 24560756
TI  - Acute phase response before treatment predicts radiation esophagitis in non-small
      cell lung cancer.
AB  - BACKGROUND AND PURPOSE: Radiation esophagitis (RE) represents an inflammatory
      reaction to radiation therapy (RT). We hypothesized that aspects of the
      physiologic acute phase response (APR) predicts RE. MATERIAL AND METHODS: We
      retrospectively analyzed 285 patients with non-small cell lung cancer (NSCLC)
      treated with definitive radiation. The primary analysis was the association of
      pretreatment lab values reflective of the APR with symptomatic (grade ? 2) RE.
      Univariate and multivariate odds ratios (ORs) were calculated to test
      associations of clinical and pretreatment lab values with RE. Optimal cutpoints
      and multivariable risk stratification groupings were determined via recursive
      partitioning analysis. RESULTS: Pretreatment platelet counts were higher and
      hemoglobin levels lower in patients who developed RE (P<0.05). Based on these two
      pre-treatment risk factors, an APR score was defined as 0 (no risk factors), 1
      (either risk factor), or 2 (both risk factors). APR score was significantly
      associated with RE in both univariate (OR = 2.3 for each point, 95% confidence
      interval [CI] 1.5-3.4, P = 0.001) and multivariate (OR = 2.1, 95% CI 1.3-3.4, P =
      0.002) analyses. CONCLUSIONS: The APR score may represent a novel metric to
      predict RE. However, pending validation in an independent dataset, caution is
      advised when interpreting these results given their retrospective and thus
      exploratory nature.

PMID- 24560757
TI  - The impact of rectal and bladder variability on target coverage during post
      prostatectomy intensity modulated radiotherapy.
AB  - BACKGROUND AND PURPOSE: Accuracy when delivering post-prostatectomy intensity
      modulated radiotherapy (IMRT) is crucial. The aims of this study were to quantify
      prostate bed movement and determine what amount of bladder or rectum size
      variation creates the potential for geographic miss. METHODS AND MATERIALS: The
      Cone Beam CT (CBCT) images (n=377) of forty patients who received post
      prostatectomy IMRT with daily on-line alignment to bony anatomy were reviewed.
      Prostate bed movement was estimated using the location of surgical clips in the
      upper and lower sections of the PTV and correlated with rectal and bladder
      filling (defined as changes in the cross sectional diameter at defined levels).
      The number of potential geographic misses caused by bladder and rectum variation
      was calculated assuming a uniform CTV to PTV expansion of 1cm except 0.5 cm
      posteriorly. RESULTS: Variations in bladder filling of >2 cm larger, +/-1 cm, or
      >2 cm smaller occurred in 3.4%, 56.2%, and 15.1% of images respectively with
      potential geographic misses in the upper prostate bed of 61.5%, 9.9% and 26.3%
      respectively. Variations in rectal filling in the upper prostate bed of >1.5 cm
      larger, 1.5 cm larger to 1cm smaller, and >1cm smaller occurred in 17.2%, 75.6%,
      and 7.2% of images respectively. These variations resulted in geographic misses
      in the upper prostate bed in 29.2%, 12.3%, and 63.0% of images respectively.
      Variations in bladder and rectal filling in the lower prostate bed region had
      minimal impact on geographic misses. CONCLUSIONS: Bladder and rectal size changes
      at treatment affect prostate bed coverage, especially in the upper aspect of the
      prostate bed. The greatest potential for geographic miss occurred when either the
      bladder increased in size or when the rectum became smaller. Ensuring a full
      bladder and empty rectum at simulation will minimise this risk. Our data also
      support anisotropic PTV margins with larger margins superiorly than inferiorly.

PMID- 24560758
TI  - Does family history of prostate cancer affect outcomes following radiotherapy?
AB  - OBJECTIVE: To examine family history (FH) as a prognostic factor following
      radiotherapy (RT). MATERIALS AND METHODS: Between 1989 and 2007, 1711 men with
      clinically localized prostate cancer and complete family history who had received
      RT (median RT dose=74Gy) without androgen deprivation therapy were analyzed. FH
      was defined as any prostate cancer in a first degree relative. For the
      biochemical failure (BF) outcome, this sample size has 85% power to detect a
      hazard ratio of 1.56 for positive versus negative FH. RESULTS: With a median
      follow-up of 71 months, there was no significant difference in the distribution
      of Gleason score (GS) or prostate specific antigen (PSA) based on FH. A positive
      FH was not an independent predictor of BF, distant metastasis (DM), prostate
      cancer specific mortality (PCSM), or overall mortality (OM) in Cox proportional
      multivariable analysis. On further analysis in a Cox proportional multivariable
      analysis, men with two or more first degree relatives with prostate cancer had a
      significantly higher likelihood of BF and DM than those with no FH, although
      there was no difference in PCSM or OM. Men with a positive FH (23%) were more
      likely to be younger, have a lower PSA, and non-palpable disease. There was no
      interaction between a positive FH and neither race nor treatment era (pre-PSA vs.
      PSA era). CONCLUSIONS: A positive FH is not a prognostic factor following RT and
      should not alter standard treatment recommendations. Patients with two or more
      first degree relatives with prostate cancer had a higher likelihood of BF and DM,
      but there was no effect on survival. There was no interaction between a positive
      FH and African American race or treatment era. A positive FH was however,
      associated with more favorable PSA values and T-stage that may be the result of
      earlier screening.

PMID- 24560759
TI  - Differences in delineation guidelines for head and neck cancer result in
      inconsistent reported dose and corresponding NTCP.
AB  - PURPOSE: To test the hypothesis that delineation of swallowing organs at risk
      (SWOARs) based on different guidelines results in differences in dose-volume
      parameters and subsequent normal tissue complication probability (NTCP) values
      for dysphagia-related endpoints. MATERIALS AND METHODS: Nine different SWOARs
      were delineated according to five different delineation guidelines in 29
      patients. Reference delineation was performed according to the guidelines and
      NTCP-models of Christianen et al. Concordance Index (CI), dosimetric
      consequences, as well as differences in the subsequent NTCPs were calculated.
      RESULTS: The median CI of the different delineation guidelines with the reference
      guidelines was 0.54 for the pharyngeal constrictor muscles, 0.56 for the
      laryngeal structures and 0.07 for the cricopharyngeal muscle and esophageal inlet
      muscle. The average difference in mean dose to the SWOARs between the guidelines
      with the largest difference (maxDeltaD) was 3.5+/-3.2Gy. A mean DeltaNTCP of
      2.3+/-2.7% was found. For two patients, DeltaNTCP exceeded 10%. CONCLUSIONS: The
      majority of the patients showed little differences in NTCPs between the different
      delineation guidelines. However, large NTCP differences >10% were found in 7% of
      the patients. For correct use of NTCP models in individual patients, uniform
      delineation guidelines are of great importance.

PMID- 24560760
TI  - Hypofractionated conformal radiotherapy for pediatric diffuse intrinsic pontine
      glioma (DIPG): a randomized controlled trial.
AB  - BACKGROUND: The pediatric diffuse intrinsic pontine glioma (DIPG) outcome remains
      dismal despite multiple therapeutic attempts. PURPOSE: To compare the results of
      treatment of pediatric diffuse intrinsic pontine glioma (DIPG) using
      hypofractionated versus conventional radiotherapy. PATIENTS AND METHODS: Seventy
      one newly diagnosed DIPG children were randomized into hypofractionated (HF)
      (39Gy/13 fractions in 2.6weeks) and conventional (CF) arm (54Gy/30 fractions in
      6weeks). RESULTS: The median and one-year overall survival (OS) was 7.8months and
      36.4+/-8.2% for the hypofractionated arm, and 9.5 and 26.2+/-7.4% for the
      conventional arm respectively. The 18-month OS difference was 2.2%. The OS hazard
      ratio (HR) was 1.14 (95% CI: 0.70-1.89) (p=0.59). The hypofractionated arm had a
      median and one-year progression-free survival (PFS) of 6.6months and 22.5+/-7.1%,
      compared to 7.3 and 17.9+/-7.1% for the conventional arm. The PFS HR was 1.10
      (95% CI: 0.67-1.90) (p=0.71). The 18-month PFS difference was 1.1%. These
      differences exceed the non-inferiority margin. The immediate and delayed side
      effects were not different in the 2 arms. CONCLUSIONS: Hypofractionated
      radiotherapy offers lesser burden on the patients, their families and the
      treating departments, with nearly comparable results to conventional
      fractionation, though not fulfilling the non-inferiority assumption.

PMID- 24560761
TI  - Is there a role for proton therapy in the treatment of hepatocellular carcinoma?
      A systematic review.
AB  - This paper aimed to review the literature concerning the use of proton therapy
      systematically in the treatment of hepatocellular carcinoma, focusing on clinical
      results and technical issues. The literature search was conducted according to a
      specific protocol in the Medline and Scopus databases by two independent
      researchers covering the period of 1990-2012. Both clinical and technical studies
      referring to a population of patients actually treated with protons were
      included. The PRISMA guidelines for reporting systematic reviews were followed. A
      final set of 16 studies from seven proton therapy institutions worldwide were
      selected from an initial dataset of 324 reports. Seven clinical studies, five
      reports on technical issues, three studies on treatment related toxicity and one
      paper reporting both clinical results and toxicity analysis were retrieved. Four
      studies were not published as full papers. Passive scattering was the most
      adopted delivery technique. More than 900 patients with heterogeneous stages of
      disease were treated with various fractionation schedules. Only one prospective
      full paper was found. Local control was approximately 80% at 3-5years, average
      overall survival at 5years was 32%, with data comparable to surgery in the most
      favorable groups. Toxicity was low (mainly gastrointestinal). Normal liver
      V0Gy<30%volume and V30Gy<18-25%volume were suggested as cut-off values for
      hepatic toxicity. The good clinical results of the selected papers are
      counterbalanced by a low level of evidence. However, the rationale to enroll
      patients in prospective studies appears to be strong. 

PMID- 24560762
TI  - A modelled comparison of prostate cancer control rates after high-dose-rate
      brachytherapy (3145 multicentre patients) combined with, or in contrast to,
      external-beam radiotherapy.
AB  - BACKGROUND AND PURPOSE: To analyse biochemical relapse-free-survival results for
      prostate cancer patients receiving combined external beam and high-dose-rate
      brachytherapy, in comparison with expected results using projections based on
      dose/fractionation/response parameter values deduced from a previous external
      beam-alone 5969-patient multicentre dataset. MATERIAL AND METHODS: Results on a
      total of 3145 prostate cancer patients receiving brachytherapy (BT) as part or
      all of their treatment were collected from 10 institutions, and subjected to
      linear-quadratic (LQ) modelling of dose response and fractionation parameters.
      RESULTS: Treatments with BT components of less than 25Gy, 3-4 BT fractions, doses
      per BT fraction up to 6Gy, and treatment times of 3-7weeks, all gave outcomes
      expected from LQ projections of the external-beam-alone data (alpha/beta=1.42Gy).
      However, BT doses higher than 30Gy, 1-2 fractions, 9 fractions (BT alone), doses
      per fraction of 9-15Gy, and treatment in only 1week (one example), gave local
      control levels lower than the expected levels by up to ~35%. CONCLUSIONS: There
      are various potential causes of the lower-than-projected control levels for some
      schedules of brachytherapy: it seems plausible that cold spots in the
      brachytherapy dose distribution may be contributory, and the applicability of the
      LQ model at high doses per fraction remains somewhat uncertain. The results of
      further trials may help elucidate the true benefit of hypofractionated high-dose
      rate brachytherapy.

PMID- 24560763
TI  - Intra- and interfractional variations in geometric arrangement between lung
      tumours and implanted markers.
AB  - PURPOSE: To quantify the intra- and interfractional variations between lung
      tumours and implanted markers. MATERIALS AND METHODS: Gold markers were implanted
      transbronchially around a lung tumour in fifteen patients. They underwent four
      dimensional computed tomography scans twice, and the centroids of the tumour and
      markers were determined. Intrafractional variations were defined as the residual
      tumour motions relative to the markers due to respiration from the end-exhale
      phase. Interfractional variations were defined as the residual setup errors after
      correction for the position of the implanted markers in end-exhale phase images.
      RESULTS: The intrafractional variations differed between patients. The root mean
      squares of standard deviations for each phase were 0.6, 0.9, and 1.5mm in the
      right-left, anterior-posterior, and superior-inferior directions, respectively.
      The maximum difference in intrafractional variation among 10 phases was
      correlated with the amplitude of tumour motion in all directions and the tumour
      marker distance in the anterior-posterior and superior-inferior directions. The
      interfractional variations were within 2.5mm. CONCLUSIONS: The intrafractional
      variations differed according to the amount of tumour motion and the tumour
      marker distance. Additionally, interfractional variations of up to 2.5mm were
      observed. Thus, a corresponding margin should be considered during implanted
      marker-based beam delivery to account for these variations.

PMID- 24560764
TI  - Low incidence of melanoma brain metastasis in the hippocampus.
AB  - AIMS: ANZMTG 01.07 WBRTMel is a phase 3 randomized trial to address the role of
      whole brain radiation therapy (WBRT) after local treatment of 1-3 melanoma brain
      metastases. Modern radiation therapy technologies can now conformally spare the
      hippocampus during WBRT and therefore potentially reduce the risk of
      neurocognitive deficit. The aims of this study were to report the prevalence of
      melanoma metastases within the hippocampal sparing region and to identify
      variables that correlate with the presence of metastases within the hippocampal
      sparing region. METHODS: The pre-local treatment MRI scans of 77 eligible WBRTMel
      patients were used to contour the individual metastasis and the hippocampus. The
      volume, location and closest distance of each metastasis to the hippocampus were
      recorded. Binary logistic regression was performed to assess the influence of
      factors on the location of a metastasis within 5mm of the hippocampus. RESULTS:
      The median age was 61 and 66% were male. The distribution of the 115 metastases
      was frontal (50, 43.5%), parietal (23, 20.0%), temporal (13, 11.2%), occipital
      (18, 15.7%), cerebellum (10, 8.6%) and pineal gland (1, 1.0%). The median
      aggregate volume of the metastasis was 3516mm(3). None of the metastases were
      within the hippocampus. Four patients (5.2%) had metastases within 5mm of the
      hippocampus. The median distance from metastasis to the nearest hippocampus was
      37.2mm. Only the total volume of metastases was a significant predictor for the
      risk of a metastasis within the hippocampal sparing region (OR 1.071, 95% CI:
      1.003-1.144, p=0.040). CONCLUSIONS: This study confirmed a low incidence of
      melanoma metastasis in the hippocampal sparing region at diagnosis. Given the
      lack of randomized data on the safety and benefit of hippocampal sparing WBRT,
      the current WBRTMel trial provides the opportunity to explore the feasibility of
      this technique.

PMID- 24560765
TI  - Mid-ventilation based PTV margins in Stereotactic Body Radiotherapy (SBRT): a
      clinical evaluation.
AB  - PURPOSE: Large tumor motion leads to large treatment volumes with an Internal
      Target Volume (ITV) based approach, whereas mid-ventilation (MidV) based Planning
      Target Volumes (PTV) margins typically lead to smaller treatment volumes. The
      purpose of this study was to evaluate the MidV approach on clinical outcome data
      of Stereotactic Body Radiotherapy (SBRT) in NSCLC. METHODS AND MATERIALS: 297
      patients with 314 peripheral tumors treated from 2006 to 2012 were
      retrospectively analyzed. In all patients a 4D-CT was acquired and the MidV-CT
      scan was selected. Tumor amplitudes were determined in left-right (LR), cranio
      caudal (CC) and anterior-posterior (AP) direction, to calculate patient specific
      PTV margins. RESULTS: The median LR, CC and AP tumor amplitudes were 2mm (0-16
      mm), 4mm (0-39 mm) and 3mm (0-18 mm), respectively, yielding a median CTV-to-PTV
      margin of 8mm. An ITV+5mm based PTV margin would have been bigger in 47% of the
      patients. After a median follow up of 22 months, local recurrence occurred in six
      patients (2%). Two year LC and OS were 98% and 67%, respectively. CONCLUSIONS:
      Using the MidV approach combined with online image guidance an excellent LC of
      98% was established with SBRT. This provides clinical support that incorporating
      respiratory motion into the PTV margin is a safe approach.

PMID- 24560766
TI  - Factors influencing survival outcome for radiotherapy for biliary tract cancer: a
      multicenter retrospective study.
AB  - PURPOSE: To seek for the possible factors influencing overall survival (OS) with
      radiotherapy (RT) for biliary tract cancer. MATERIALS AND METHODS: Data were
      collected retrospectively from RT database of 31 institutions in Japan. All
      patients underwent at least external beam RT. The factors influencing OS were
      investigated. RESULTS: Data of 498 patients were analyzed. Median OS of the 212
      patients who underwent surgery was significantly better than that of the 286
      patients without surgery (31 vs. 15 months, p<0.001). The OS for the R0 or R1
      resection group was significantly longer than that for the R2 or non-surgery
      group, as well as for n0 compared to n1 (all p<0.001). Chemoradiotherapy (CRT),
      both sequential and concurrent, resulted in a better OS than RT alone for the n1
      group (31 vs. 13 months, p<0.001), and marginally better for the R0/R1 group
      (p=0.065; p=0.054 for concurrent CRT). However, no such benefit was observed for
      the R2/non-surgical patients. Multivariate analysis identified performance
      status, clinical stage, and surgery as significant factors. CONCLUSION: Surgery,
      especially R0/R1 resection, seemed as the gold standard for treatment of biliary
      tract cancer including RT, even in the highly heterogeneous population obtained
      from the multicenter retrospective study. The possibility was shown that CRT
      yielded better survival benefit especially for n1 patients. We recommend that
      future prospective trials include an arm of adjuvant CRT at least for n1 and
      possibly R0/R1 patients.

PMID- 24560768
TI  - Influence of experimental infection by Haemonchus contortus on
      acetylcholinesterase activity in lymphocytes of lambs.
AB  - The aim of this study was to evaluate the acetylcholinesterase (AChE) activity in
      lymphocytes of lambs experimentally infected by Haemonchus contortus. A total of
      14 healthy lambs were used, divided into two groups of seven animals each. Group
      A (negative control) represented the uninfected animals, and Group B (positive
      control) was formed by animals infected with 15,000 larvae of H. contortus. Blood
      was drawn on the days 15, 45 and 75 post-infection (PI) in order to perform the
      white blood cells (WBC) count, as well as the evaluation of AChE activity in
      lymphocytes. Parasitological stool exam (eggs per gram of feces - EPG) was
      performed on the same days to follow up the evolution of the infection. On day 15
      PI it was verified negative EPG; however, on days 45 and 75 PI it was observed
      positive EPG only in the animals of group B. In the three evaluated periods was
      observed a lower number of leukocytes, associated with decreased lymphocytes and
      neutrophils in lambs infected by this gastrointestinal nematodes. Lambs infected
      with H. contortus showed significant (P<0.01) lower AChE activity in lymphocytes
      compared uninfected. Statistically, there was a positive correlation (P<0.05)
      between AChE activity in lymphocytes and number of lymphocytes (r=0.69). The
      lymphocytes are cells with direct participation in the cholinergic system;
      therefore, based on these results, it can be concluded that the experimental
      infection with H. contortus influences the number of lymphocytes, and
      consequently the AChE activity in these cells. 

PMID- 24560767
TI  - The lamprey: a jawless vertebrate model system for examining origin of the neural
      crest and other vertebrate traits.
AB  - Lampreys are a group of jawless fishes that serve as an important point of
      comparison for studies of vertebrate evolution. Lampreys and hagfishes are
      agnathan fishes, the cyclostomes, which sit at a crucial phylogenetic position as
      the only living sister group of the jawed vertebrates. Comparisons between
      cyclostomes and jawed vertebrates can help identify shared derived (i.e.
      synapomorphic) traits that might have been inherited from ancestral early
      vertebrates, if unlikely to have arisen convergently by chance. One example of a
      uniquely vertebrate trait is the neural crest, an embryonic tissue that produces
      many cell types crucial to vertebrate features, such as the craniofacial
      skeleton, pigmentation of the skin, and much of the peripheral nervous system
      (Gans and Northcutt, 1983). Invertebrate chordates arguably lack unambiguous
      neural crest homologs, yet have cells with some similarities, making comparisons
      with lampreys and jawed vertebrates essential for inferring characteristics of
      development in early vertebrates, and how they may have evolved from
      nonvertebrate chordates. Here we review recent research on cyclostome neural
      crest development, including research on lamprey gene regulatory networks and
      differentiated neural crest fates. 

PMID- 24560769
TI  - Evaluation of the non-catalytic binding function of Ts26GST a glutathione
      transferase isoform of Taenia solium.
AB  - Taenia solium glutathione transferase isoform of 26.5 kDa (Ts26GST) was observed
      to bind non-catalytically to porphyrins, trans-trans-dienals, bile acids and
      fatty acids, as assessed by inhibition kinetics, fluorescence spectroscopy and
      competitive fluorescence assays with 8-anilino-1-naphthalene sulfonate (ANS). The
      quenching of Ts26GST intrinsic fluorescence allowed for the determination of the
      dissociation constants (KD) for all ligands. Obtained data indicate that Ts26GST
      binds to all ligands but with different affinity. Porphyrins and lipid peroxide
      products inhibited Ts26GST catalytic activity up to 100% in contrast with only 20
      30% inhibition observed for bile acids and two saturated fatty acids. Non
      competitive type inhibition was observed for all enzyme inhibitor ligands except
      for trans-trans-2,4-decadienal, which exhibited uncompetitive type inhibition.
      The dissociation constant value KD = 0.7 MUM for the hematin ligand, determined
      by competitive fluorescence assays with ANS, was in good agreement with its
      inhibition kinetic value Ki = 0.3 MUM and its intrinsic fluorescence quenching KD
      = 0.7 MUM. The remaining ligands did not displace ANS from the enzyme suggesting
      the existence of different binding sites. In addition to the catalytic activity
      of Ts26GST the results obtained suggest that the enzyme exhibits a ligandin
      function with broad specificity towards nonsubstrate ligands.

PMID- 24560770
TI  - Toxoplasma gondii: prevalence in species and genotypes of British bats
      (Pipistrellus pipistrellus and P. pygmaeus).
AB  - Few studies have investigated Toxoplasma gondii infections in bat populations and
      none have reported its presence in protected British bat species. Using a
      collection of dead/euthanased bats collected from Lancashire, UK, two species of
      bats (Pipistrellus pipistrellus and Pipistrellus pygmaeus) were tested using a
      highly sensitive SAG1-PCR method specific for detection of T. gondii DNA (n=77;
      71 P. pipistrellus and 6 P. pygmaeus). Whilst some potential bias may exist in
      the sampling strategy, an overall prevalence of 10.39% (+/-6.06%; 95%CI) was
      detected. All P. pipistrellus, were also genotyped using eleven polymorphic
      microsatellite loci to determine their local population structure. The programme
      STRUCTURE revealed that the majority of individuals (83%) were derived from one
      interbreeding population, and the remaining individuals (17%) had mixed genetic
      origins. There was no significant difference in the frequency of T. gondii
      infection or geographical distribution between subclusters. As all British bats
      are insectivorous, the routes of infection with T. gondii remain elusive.
      However, the locally large and panmictic gene pool suggests that intraspecies
      transmission could be applicable. 

PMID- 24560772
TI  - Activation of beta-catenin by inhibitors of glycogen synthase kinase-3
      ameliorates cisplatin-induced cytotoxicity and pro-inflammatory cytokine
      expression in HEI-OC1 cells.
AB  - Cisplatin is used in the treatment of a wide variety of solid tumors, but its use
      is limited by its serious adverse effects, including ototoxicity. Glycogen
      synthase kinase-3 (GSK-3) is a ubiquitously expressed serine/threonine kinase
      that regulates a variety of cellular functions by phosphorylating its substrates.
      However, the otoprotective effect of GSK-3 inhibitors is poorly understood. Here,
      we investigated whether GSK-3 is involved in cisplatin-induced ototoxicity in HEI
      OC1 cells and organs of Corti (OCs). GSK-3 inhibitors suppressed cisplatin
      induced apoptosis determined by decreased p53 activity, and also decreased
      expression of PARP and p53 target genes such as p21 and PUMA. The effect of GSK-3
      inhibitors was mediated by markedly increased nuclear beta-catenin that in turn
      blocked nuclear translocation of NF-kappaB. siRNA-mediated beta-catenin knockdown
      markedly increased the expression of NF-kappaB target genes, such as TNF-alpha
      and IL-6. Our data suggest that the GSK-3/beta-catenin pathway may play a central
      role in cisplatin-mediated cytotoxicity in HEI-OC1 cells and hair cells of OCs in
      vitro. 

PMID- 24560771
TI  - Sex differences in extinction recall in posttraumatic stress disorder: a pilot
      fMRI study.
AB  - Recent research has found that individuals with posttraumatic stress disorder
      (PTSD) exhibit an impaired memory of fear extinction compounded by deficient
      functional activation of key nodes of the fear network including the amygdala,
      hippocampus, ventromedial prefrontal cortex (vmPFC) and dorsal anterior cingulate
      cortex (dACC). Research has shown these regions are sexually dimorphic and
      activate differentially in healthy men and women during fear learning tasks. To
      explore biological markers of sex differences following exposure to psychological
      trauma, we used a fear learning and extinction paradigm together with functional
      magnetic resonance imaging (fMRI) and skin conductance response (SCR) to assess
      31 individuals with PTSD (18 women; 13 men) and 25 matched trauma-exposed healthy
      control subjects (13 women; 12 men). Whereas no sex differences appeared within
      the trauma-exposed healthy control group, both psychophysiological and neural
      activation patterns within the PTSD group indicated deficient recall of
      extinction memory among men and not among women. Men with PTSD exhibited
      increased activation in the left rostral dACC during extinction recall compared
      with women with PTSD. These findings highlight the importance of tracking sex
      differences in fear extinction when characterizing the underlying neurobiological
      mechanisms of PTSD psychopathology. 

PMID- 24560773
TI  - Responses of the steroidogenic pathway from exposure to methyl-tert-butyl ether
      and tert-butanol.
AB  - Methyl tertiary-butyl ether (MTBE) is a solvent and fuel additive included in
      reformulated gasoline to increase combustion efficiency. While widespread use in
      motor fuels in the U.S. was discontinued after MTBE was detected in surface and
      ground waters due to concerns about environmental persistence and water quality,
      it is still manufactured in the U.S. for export. Questions concerning the
      etiology of rat Leydig cell and mouse liver tumors identified in extremely high
      dose cancer studies have led to an interest in evaluating potential hormonal
      imbalances and endocrine system involvement. To address the possibility that MTBE
      or its metabolite, tert-butanol (TBA), are interacting with components of the
      endocrine system that are involved in steroidogenesis a number of targeted
      experiments were performed focusing mostly on the primary gonadal steroids,
      estradiol and testosterone. The goal of the experiments was to gain a better
      understanding of potential interactions with the steroidogenic pathway, including
      effects specifically on aromatase, the P450 enzyme that converts testosterone to
      estradiol. In three GLP-compliant in vitro guideline studies, MTBE and TBA were
      classified as non-binders to the androgen receptor, were classified negative for
      effects on testosterone and estradiol in the steroidogenesis assay, and were
      classified as non-inhibitors of aromatase activity. In three 14-day in vivo
      experiments involving gavaging of male Sprague-Dawley rats with doses of MTBE
      ranging from 400 to 1,500 mg/kg bw/day, the lack of definitive and consistent
      supporting statistically significant findings in steroid hormone measurements and
      aromatase activity and mRNA measured in liver and testis microsomes further
      suggested that it is unlikely that MTBE is interacting with the endocrine system
      directly. Evidence of other underlying systemic effects were also seen, including
      reduced body weight gain, increased adrenal weights, and elevated corticosterone
      suggestive of a more general stress response. Taken together, the results from
      these studies suggest that MTBE and TBA do not directly impact the steroidogenic
      pathways involved in estrogen and androgen production.

PMID- 24560774
TI  - Influence of inocula with prior hydrocarbon exposure on biodegradation rates of
      diesel, synthetic diesel, and fish-biodiesel in soil.
AB  - To achieve effective bioremediation within short warm seasons of cold climates,
      microbial adaptation periods to the contaminant should be brief. The current
      study investigated growth phases for soil spiked with diesel, Syntroleum, or fish
      biodiesel, using microbial inocula adapted to the specific substrates. For
      modeling hydrocarbon degradation, multi-phase first order kinetics was assumed,
      comparing linear regression with nonlinear parameter optimization of rate
      constants and phase durations. Lag phase periods of 5 to >28d were followed by
      short and intense exponential growth phases with high rate constants (e.g. from
      kFish=0.0013+/-0.0002 to kSyntr=0.015+/-0.001d(-1)). Hydrocarbon mineralization
      was highest for Syntroleum contamination, where up to three times higher
      cumulative CO2 production was achieved than for diesel fuel, with fish biodiesel
      showing initially the slowest degradation. The amount of hydrocarbons recovered
      from the soil by GC-MS decreased in the order fish biodiesel>diesel>Syntroleum.
      During initial weeks, biodegradation was higher for microbial inocula adapted to
      a specific fuel type, whereby the main effect of the inoculum was to shorten the
      lag phase duration; however, the inoculum's importance diminished after daily
      respiration peaked. In conclusion, addition of an inoculum to increase
      biodegradation rates was not necessary. 

PMID- 24560775
TI  - Simultaneous identification and quantification of 4-cumylphenol, 2,4-bis
      (dimethylbenzyl)phenol and bisphenol A in prawn Macrobrachium rosenbergii.
AB  - Bisphenol A (BPA), 4-cumylphenol (4-CP) and 2,4-bis-(dimethylbenzyl)phenol (2,4
      DCP) are all high production volume chemicals and widely used in plastic and
      other consumer products. During the past two decades, BPA has attracted a great
      deal of scientific and public attention due to its presence in the environment
      and estrogenic property. Although 4-CP and 2,4-DCP are much more estrogenic and
      toxic than BPA, little information is available about their occurrence and fate
      in the environment. In this study, a rapid, selective, accurate and reliable
      analytical method was developed for the simultaneous determination of 4-CP, 2,4
      DCP and BPA in prawn Macrobrachium rosenbergii. The method comprises an
      ultrasound-accelerated extraction followed by capillary gas chromatographic (GC)
      separation. The detection limits range from 1.50 to 36.4 ng kg(-1) for the three
      alkylphenols. The calibration curves are linear over the concentration range
      tested with the coefficients of determination, R(2), greater than 0.994. The
      developed method was successfully applied to the simultaneous determination of 4
      CP, 2,4-DCP and BPA in prawn samples. The peak identification was confirmed using
      GC-MS. Bisphenol A, 2,4-bis-(dimethylbenzyl)phenol and 4-cumylphenol were found
      in prawn samples in the concentration ranges of 0.67-5.51, 0.36-1.61, and 0.00
      1.96 ng g(-1) (wet weight), respectively. All relative standard deviations are
      less than 4.8%. At these environmentally relevant concentration levels, 4-CP, 2,4
      DCP and BPA may affect the reproduction and development of aquatic organisms,
      including negative influence on crustaceans' larval survival, molting,
      metamorphosis and shell hardening. This is the first study reported on the
      occurrence of 4-CP, 2,4-DCP and BPA in prawn M. rosenbergii.

PMID- 24560776
TI  - Occurrence of carbamazepine and five metabolites in an urban aquifer.
AB  - This paper deals with urban groundwater contaminated with carbamazepine (CBZ) and
      five of its human metabolites in Barcelona. Groundwater samples were accordingly
      collected in the aquifers of Poble Sec and Besos River Delta. Higher
      concentrations and more compounds were found in the Besos River Delta aquifer,
      which is recharged by a river contaminated with treated effluent from numerous
      treatment plants. By contrast, the urban area of Poble Sec presented lower
      concentrations and fewer compounds. The results showed that CBZ could be
      attenuated in the Poble Sec aquifer since concentrations in groundwater were
      lower than those evaluated from mixing of the recharge sources. Conversely, CBZ
      and its human metabolites were not removed under the reducing conditions of the
      Besos River Delta aquifer probably because of the short residence time in this
      aquifer. 

PMID- 24560777
TI  - Sometimes blood is essential--a simulation based approach to optimizing massive
      transfusion.

PMID- 24560778
TI  - The effect of centrally injected CDP-choline on respiratory system; involvement
      of phospholipase to thromboxane signaling pathway.
AB  - CDP-choline is an endogenous metabolite in phosphatidylcholine biosynthesis.
      Exogenous administration of CDP-choline has been shown to affect brain metabolism
      and to exhibit cardiovascular, neuroendocrine neuroprotective actions. On the
      other hand, little is known regarding its respiratory actions and/or central
      mechanism of its respiratory effect. Therefore the current study was designed to
      investigate the possible effects of centrally injected CDP-choline on respiratory
      system and the mediation of the central cholinergic receptors and phospholipase
      to thromboxane signaling pathway on CDP-choline-induced respiratory effects in
      anaesthetized rats. Intracerebroventricularly (i.c.v.) administration of CDP
      choline induced dose- and time-dependent increased respiratory rates, tidal
      volume and minute ventilation of male anaesthetized Spraque Dawley rats. I.c.v.
      pretreatment with atropine failed to alter the hyperventilation responses to CDP
      choline whereas mecamylamine, cholinergic nicotinic receptor antagonist,
      mepacrine, phospholipase A2 inhibitor, and neomycin phospholipase C inhibitor,
      blocked completely the hyperventilation induced by CDP-choline. In addition,
      central pretreatment with furegrelate, thromboxane A2 synthesis inhibitor, also
      partially blocked CDP-choline-evoked hyperventilation effects. These data show
      that centrally administered CDP-choline induces hyperventilation which is
      mediated by activation of central nicotinic receptors and phospholipase to
      thromboxane signaling pathway. 

PMID- 24560779
TI  - Sublingual administration of a helper-dependent adenoviral vector expressing the
      codon-optimized soluble fusion glycoprotein of human respiratory syncytial virus
      elicits protective immunity in mice.
AB  - Sublingual (s.l.) immunization has been described as a convenient and safe way to
      induce mucosal immune responses in the respiratory and genital tracts. We
      constructed a helper-dependent adenoviral (HDAd) vector expressing a condon
      optimized soluble fusion glycoprotein (sFsyn) of respiratory syncytial virus
      (HDAd-sFsyn) and explored the potential of s.l. immunization with HDAd-sFsyn to
      stimulate immune responses in the respiratory mucosa. The RSV specific systemic
      and mucosal immune responses were generated in BALB/c mice, and the serum IgG
      with neutralizing activity was significantly elevated after homologous boost with
      s.l. application of HDAd-sFsyn. Humoral immune responses could be measured even
      14weeks after a single immunization. Upon challenge, s.l. immunization with HDAd
      sFsyn displayed an effective protection against RSV infection. These findings
      suggest that s.l. administration of HDAd-sFsyn acts as an effective and safe
      mucosal vaccine against RSV infection, and may be a useful tool in the prevention
      of RSV infection. 

PMID- 24560780
TI  - Easy-to-use rapid gene amplification method for direct detection of RNA and DNA
      viruses in sera and feces from various animals.
AB  - The development of rapid and simple gene amplification tests is required for
      detection of pathogens to prevent transmission of infectious diseases between
      animals or from animals to humans. An easy-to-use rapid gene amplification method
      that can directly detect RNA and DNA viruses in clinical samples was developed.
      This method is based on combining loop-mediated isothermal amplification (LAMP)
      or reverse transcription-LAMP (RT-LAMP) and RNA GEM Tissue, a thermophilic enzyme
      that extracts nucleic acid by quickly digesting proteins and ribonucleases. The
      authors named these methods GEM LAMP and GEM RT-LAMP. These methods were able to
      detect viral DNA and RNA within 70 min in a single tube using only a water bath.
      The detection capacities were 10-100-fold more sensitive than those of previously
      established LAMP and RT-LAMP methods. The GEM LAMP and GEM RT-LAMP methods were
      used to detect macroscopically the presence of DNA and RNA viruses in sera or
      fecal samples from cattle, pigs, horses, dolphins, penguins, and sea lions using
      SYBR green I. The GEM LAMP and GEM RT-LAMP methods thus have considerable
      versatility as tools for detecting pathogens and are applicable to basic human
      and veterinary medicine, environmental hygiene, and point-of-care-testing.

PMID- 24560781
TI  - Performance of two real-time PCR assays for hepatitis B virus DNA detection and
      quantitation.
AB  - In-house developed real-time PCR (qPCR) techniques could be useful conjunctives
      to the management of hepatitis B virus (HBV) infection in resource-limited
      settings with high prevalence. Two qPCR assays (qPCR1 and qPCR2), based on
      primers/probes targeting conserved regions of the X and S genes of HBV
      respectively, were evaluated using clinical samples of varying HBV genotypes, and
      compared to the commercial Roche Cobas AmpliPrep/Cobas TaqMan HBV Test v2.0. The
      lower detection limit (LDL) was established at 104 IU/ml for qPCR1, and 91 IU/ml
      for qPCR2. Good agreement and correlation were obtained between the Roche assay
      and both qPCR assays (r = 0.834 for qPCR1; and r = 0.870 for qPCR2). Differences
      in HBV DNA load of > 0.5 Log10 IU/ml between the Roche and the qPCR assays were
      found in 49/122 samples of qPCR1, and 35/122 samples of qPCR2. qPCR1 tended to
      underestimate HBV DNA quantity in samples with a low viral load and overestimate
      HBV DNA concentration in samples with a high viral load when compared to the
      Roche test. Both molecular tools that were developed, used on an open real-time
      PCR system, were reliable for HBV DNA detection and quantitation. The qPCR2
      performed better than the qPCR1 and had the additional advantage of various HBV
      genotype detection and quantitation. This low cost quantitative HBV DNA PCR assay
      may be an alternative solution when implementing national programmes to diagnose,
      monitor and treat HBV infection in low- to middle-income countries where testing
      for HBV DNA is not available in governmental health programmes. 

PMID- 24560782
TI  - The application of a duplex reverse transcription real-time PCR for the
      surveillance of porcine reproductive and respiratory syndrome virus and porcine
      circovirus type 2.
AB  - The porcine respiratory disease complex (PRDC) is the most common disease in
      commercial pork production worldwide. Porcine circovirus type 2 (PCV2) and
      porcine reproductive and respiratory syndrome virus (PRRSV), the most important
      agents of PRDC, usually co-infect in the same pigs. In order to survey the
      prevalence of PCV2 and PRRSV in pigs of various ages, a duplex reverse
      transcription real-time PCR (DRT-rPCR) was developed and applied in the present
      study. The DRT-rPCR did not cross-react with 10 swine viruses other than PCV2 and
      PRRSV, with detection limits of 1 TCID50/ml for PCV2 and 6.3 TCID50/ml for PRRSV.
      Surveillance using DRT-rPCR together with serology revealed that in the five
      farms studied, pigs were most susceptible to PRRSV at 6-14 weeks of age, whereas
      susceptibility to PCV2 varied by the management system but was mostly at 10-14
      weeks of age. Cross analysis of viral loads versus antibody titers revealed that
      PCV2 load was affected negatively by anti-PCV2 ORF2 antibody, which constituted
      the most important non-infectious factor affecting the development of PMWS. These
      results indicated that DRT-rPCR was developed and applied successfully to the
      surveillance of PCV2 and PRRSV in the field. 

PMID- 24560783
TI  - Detection of phosphatidylserine with a modified polar head group in human
      keratinocytes exposed to the radical generator AAPH.
AB  - Phosphatidylserine (PS) is preferentially located in the inner leaflet of the
      cell membrane, and translocation of PS oxidized in fatty acyl chains to the
      outside of membrane has been reported as signaling to macrophage receptors to
      clear apoptotic cells. It was recently shown that PS can be oxidized in serine
      moiety of polar head-group. In the present work, a targeted lipidomic approach
      was applied to detecting OxPS modified at the polar head-group in keratinocytes
      that were exposed to the radical generator AAPH. Glycerophosphoacetic acid
      derivatives (GPAA) were found to be the major oxidation products of OxPS modified
      at the polar head-group during oxidation induced by AAPH-generated radicals,
      similarly to previous observations for the oxidation induced by OH radical. The
      neutral loss scan of 58Da and a novel precursor ion scan of m/z 137.1
      (HOPO3CH2COOH) allowed the recognition of GPAA derivatives in the total lipid
      extracts obtained from HaCaT cells treated with AAPH. The positive identification
      of serine head group oxidation products in cells under controlled oxidative
      conditions opens new perspectives and justifies further studies in other cellular
      environments in order to understand fully the role of PS polar head-group
      oxidation in cell homeostasis and disease.

PMID- 24560785
TI  - Evaluation of speech intelligibility in short-reverberant sound fields.
AB  - OBJECTIVE: The purpose of this study was to explore the differences in speech
      intelligibility in short-reverberant sound fields using deteriorated
      monosyllables. Generated using digital signal processing, deteriorated
      monosyllables can lack the redundancy of words, and thus may emphasize
      differences in sound fields in terms of speech clarity. METHODS: Ten participants
      without any hearing disorders identified 100 monosyllables convolved with eight
      impulse responses measured in different short-reverberant sound fields (speech
      transmission index >0.6 and reverberation time <1s), and we compared speech
      recognition scores between normal and deteriorated monosyllables. Deterioration
      was produced using low-pass filtering (cut off frequency=1600Hz). RESULTS: Speech
      recognition scores associated with the deteriorated monosyllables were lower than
      those for the normal monosyllables. In addition, scores were more varied among
      the different sound fields, although this result was not significant according to
      an analysis of variance. In contrast, the variation among sound fields was
      significant for the normal monosyllables. When comparing the intelligibility
      scores to the acoustic parameters calculated from eight impulse responses, the
      speech recognition scores were the highest when the reverberant/direct sound
      energy ratio (R/D) was balanced. CONCLUSIONS: Although our deterioration
      procedure obscured differences in intelligibility score among the different sound
      fields, we have established that the R/D is a useful parameter for evaluating
      speech intelligibility in short-reverberant sound fields.

PMID- 24560786
TI  - To the editor--ECG screening of athletes: let us not forget the "how".

PMID- 24560784
TI  - Transcriptional control of spermatogonial maintenance and differentiation.
AB  - Spermatogenesis is a multistep process that generates millions of spermatozoa per
      day in mammals. A key to this process is the spermatogonial stem cell (SSC),
      which has the dual property of continually renewing and undergoing
      differentiation into a spermatogonial progenitor that expands and further
      differentiates. In this review, we will focus on how these proliferative and
      early differentiation steps in mammalian male germ cells are controlled by
      transcription factors. Most of the transcription factors that have so far been
      identified as promoting SSC self-renewal (BCL6B, BRACHYURY, ETV5, ID4, LHX1, and
      POU3F1) are upregulated by glial cell line-derived neurotrophic factor (GDNF).
      Since GDNF is crucial for promoting SSC self-renewal, this suggests that these
      transcription factors are responsible for coordinating the action of GDNF in
      SSCs. Other transcription factors that promote SSC self-renewal are expressed
      independently of GDNF (FOXO1, PLZF, POU5F1, and TAF4B) and thus may act in non
      GDNF pathways to promote SSC cell growth or survival. Several transcription
      factors have been identified that promote spermatogonial differentiation (DMRT1,
      NGN3, SOHLH1, SOHLH2, SOX3, and STAT3); some of these may influence the decision
      of an SSC to commit to differentiate while others may promote later
      spermatogonial differentiation steps. Many of these transcription factors
      regulate each other and act on common targets, suggesting they integrate to form
      complex transcriptional networks in self-renewing and differentiating
      spermatogonia. 

PMID- 24560787
TI  - Control of neuronal morphology and connectivity: emerging developmental roles for
      gap junctional proteins.
AB  - Recent evidence indicates that gap junction (GJ) proteins can play a critical
      role in controlling neuronal connectivity as well as cell morphology in the
      developing nervous system. GJ proteins may function analogously to cell adhesion
      molecules, mediating cellular recognition and selective neurite adhesion.
      Moreover, during synaptogenesis electrical synapses often herald the later
      establishment of chemical synapses, and thus may help facilitate activity
      dependent sculpting of synaptic terminals. Recent findings suggest that the
      morphology and connectivity of embryonic leech neurons are fundamentally
      organized by the type and perhaps location of the GJ proteins they express. For
      example, ectopic expression in embryonic leech neurons of certain innexins that
      define small GJ-linked networks of cells leads to the novel coupling of the
      expressing cell into that network. Moreover, gap junctions appear to mediate
      interactions among homologous neurons that modulate process outgrowth and
      stability. We propose that the selective formation of GJs between developing
      neurons and perhaps glial cells in the CNS helps orchestrate not only cellular
      synaptic connectivity but also can have a pronounced effect on the arborization
      and morphology of those cells involved. 

PMID- 24560788
TI  - Differential ability to resist to complement lysis and invade host cells mediated
      by MBL in R4 and 860 strains of Trypanosoma cruzi.
AB  - To produce an infection Trypanosoma cruzi must evade lysis by the complement
      system. During early stages of infection, the lectin pathway plays an important
      role in host defense and can be activated by binding of mannan-binding lectin
      (MBL) to carbohydrates on the surface of pathogens. We hypothesized that MBL has
      a dual role during parasite-host cell interaction as lectin complement pathway
      activator and as binding molecule to invade the host cell. We used two polarized
      strains of T. cruzi, R4 (susceptible) and 860 (resistant) strains, to investigate
      the role of MBL in complement-mediated lysis. Interestingly R4, but not 860
      metacyclic strain, markedly increases the invasion of host cells, suggesting that
      MBL drives the invasion process while the parasite deactivates the Lectin
      complement pathway. 

PMID- 24560789
TI  - Autotaxin in the crosshairs: taking aim at cancer and other inflammatory
      conditions.
AB  - Autotaxin is a secreted enzyme that produces most of the extracellular
      lysophosphatidate from lysophosphatidylcholine, the most abundant phospholipid in
      blood plasma. Lysophosphatidate mediates many physiological and pathological
      processes by signaling through at least six G-protein coupled receptors to
      promote cell survival, proliferation and migration. The
      autotaxin/lysophosphatidate signaling axis is involved in wound healing and
      tissue remodeling, and it drives many chronic inflammatory conditions from
      fibrosis to colitis, asthma and cancer. In cancer, lysophosphatidate signaling
      promotes resistance to chemotherapy and radiotherapy, and increases both
      angiogenesis and metastasis. Research into autotaxin inhibitors is accelerating,
      both as primary and adjuvant therapy. Historically, autotaxin inhibitors had poor
      bioavailability profiles and thus had limited efficacy in vivo. This situation is
      now changing, especially since the recent crystal structure of autotaxin is now
      enabling rational inhibitor design. In this review, we will summarize current
      knowledge on autotaxin-mediated disease processes including cancer, and discuss
      recent advancements in the development of autotaxin-targeting strategies. We will
      also provide new insights into autotaxin as an inflammatory mediator in the tumor
      microenvironment that promotes cancer progression and therapy resistance. 

PMID- 24560790
TI  - p53: the barrier to cancer stem cell formation.
AB  - The role of p53 as the "guardian of the genome" in differentiated somatic cells,
      triggering various biological processes, is well established. Recent studies in
      the stem cell field have highlighted a profound role of p53 in stem cell biology
      as well. These studies, combined with basic data obtained 20 years ago, provide
      insight into how p53 governs the quantity and quality of various stem cells,
      ensuring a sufficient repertoire of normal stem cells to enable proper
      development, tissue regeneration and a cancer free life. In this review we
      address the role of p53 in genomically stable embryonic stem cells, a unique
      predisposed cancer stem cell model and adult stem cells, its role in the
      generation of induced pluripotent stem cells, as well as its role as the barrier
      to cancer stem cell formation.

PMID- 24560791
TI  - Tacrine induces apoptosis through lysosome- and mitochondria-dependent pathway in
      HepG2 cells.
AB  - Tacrine (THA) is a competitive inhibitor of cholinesterase. Administration of THA
      for the treatment of Alzheimer's disease results in a reversible hepatotoxicity
      in 30-50% of patients, as indicated by elevated alanine aminotransferase levels.
      However, the intracellular mechanisms have not yet been elucidated. In our
      previous study, we found that THA induced cytotoxicity and mitochondria
      dysfunction by ROS generation and 8-OHdG formation in mitochondrial DNA in HepG2
      cells. In this study, the mechanism underlying was further investigated. Our
      results demonstrated that THA induced dose-dependent apoptosis with cytochrome c
      release and activation of caspase-3. THA-induced apoptosis was inhibited by
      treating cells with a ROS inhibitor, YCG063. In addition, we observed that THA
      led to an early lysosomal membrane permeabilization and release of cathepsin B.
      Pretreatment with CA-074Me, a specific cathepsin B inhibitor resulted in a
      significant but not complete decrease in tacrine-induced apoptosis. These data
      suggest that tacrine-induced cell apoptosis involves both mitochondrial damage
      and lysosomal membrane destabilization, and ROS is the critical factor that
      integrates tacrine-induced mitochondrial and lysosomal death pathways. 

PMID- 24560792
TI  - Natural and human impact on the land use and soil properties of the Sikkim
      Himalayas piedmont in India.
AB  - Natural and human causes of change in land use and soil properties were studied
      in the Sikkim Himalayas piedmont over the last 150 years, with a special emphasis
      on the period 1930-2010. Analysis of historical reports, combined with the visual
      interpretation of topographic maps and satellite images, indicates that the land
      reforms related to the location of tea gardens caused rapid deforestation of the
      higher elevated terraces in the late 19th century. Continuous population growth
      between 1930 and 2010 caused a shift in the major land use changes from the
      terraces to the floodplains. As a consequence, a gradual extension of tea
      plantation and forestry development helped in stabilizing the land use of the
      terraces, while the parallel deforestation of mountain catchments and floodplains
      for rice cultivation intensified fluvial activity. The enlargement of river
      channel area by about 42% between 1930 and 2010 excluded a large part of the
      floodplains from cultivation and increased risk of soil degradation. The
      replacement of natural forest by monocultural tea and rice cultivation influenced
      the physical and chemical properties of the soil. Statistically significant
      changes were observed only in some chemical properties of the topsoil. Tea
      cultivation reduced the total carbon content by 26% and total nitrogen content by
      33% in the surface soil horizon. The influence of rice tillage on the soil
      properties is masked by the fluvial activity. The combined effect of flooding and
      rice cultivation is reflected in the lower content of total carbon and nitrogen
      in the surface of the soil, namely, 76% and 77% respectively. Taking into account
      the long-term nature of the plantation, the soil still has the capability to
      support tea production. The productivity of rice depends partly on fertilization
      levels and partly on the natural deposition of fresh sediment eroded from
      mountains.

PMID- 24560793
TI  - Is extended lymphadenectomy of beneficial therapeutic value for T2 urothelial
      cancer?

PMID- 24560794
TI  - Pseudohyperplastic adenocarcinoma of the prostate.

PMID- 24560795
TI  - MicroRNA-125b regulates osteogenic differentiation of mesenchymal stem cells by
      targeting Cbfbeta in vitro.
AB  - Differentiation of mesenchymal stem cells (MSCs) into a specific lineage is
      firmly and precisely regulated via crucial transcription factors and signaling
      cascades, but the accurate mechanisms still need to be revealed. MicroRNAs
      (miRNA) negativity regulates the target mRNA protein synthesis to regulate
      various kinds of biological processes. In the present study we investigate miRNAs
      mediated regulatory mechanisms of osteoblastic differentiation in C3H10T1/2 cells
      and we identified that the level of miR-125b expression was obviously decreased
      compared with undifferentiated ones during differentiation process. Subsequently,
      dual-luciferase reporter gene assay data demonstrated that miR-125b targets a
      putative binding site in the 3'-UTR of Cbfbeta gene, a key transcription factor
      for osteogenesis. We observed over and interferential expression of miR-125b down
      regulate for Cbfbeta protein in C3H10T1/2 cells and the over-expression decrease
      the mRNA levels of three osteoblastic marker genes, alkaline phosphatase (ALP),
      osteocalcin (OCN), osteopontin (OPN) by BMP-2-induced, whereas, anti-miR-125b
      increased the expression of these marker genes and hence up-regulated mRNA levels
      of Cbfbeta. It is concluded from the result that miR-125b is a key regulatory
      factor of osteoblastic differentiation by directly targeting Cbfbeta and
      indirectly acting on Runx2 at an early stage osteoblastic differentiation.

PMID- 24560796
TI  - Alkali burn versus suture-induced corneal neovascularization in C57BL/6 mice: an
      overview of two common animal models of corneal neovascularization.
AB  - The purpose of the present study was to quantify and compare corneal hem- and
      lymphangiogenesis between alkali burn and suture-induced corneal
      neovascularization (CNV) in two commonly used mouse strains. A retrospective
      analysis was performed on C57BL/6 and FVB neovascularized corneas. CNV was
      induced by surface caustication with NaOH or intrastromal placement of three 10.0
      nylon sutures. Hemangiogenesis and lymphangiogenesis extent was calculated on
      whole mounted corneas by CD31 and LYVE1 immunofluorescence analysis. Blood vessel
      growth was similar between alkali burn and suture-induced CNV in C57BL/6 mice,
      and between C57BL/6 and FVB sutured strains. On the contrary, corneal
      lymphangiogenesis was more pronounced in the C57BL/6 sutured mice versus the
      alkali burn group, and in the FVB strain versus both C57BL/6 models. These
      results indicate that significant differences occur in lymphangiogenesis, but not
      hemangiogenesis, in the alkali burn and suture-induced models in C57BL/6 mice.
      Furthermore, lymphangiogenesis is more pronounced in the albino (FVB) strain
      after suture placement. We suggest that the suture model has a number of
      advantages and may be preferentially used to study corneal lymphangiogenesis. 

PMID- 24560798
TI  - Response to "Lightwand-guided nasotracheal intubation in oromaxillofacial surgery
      patients".

PMID- 24560799
TI  - A functional polyester carrying free hydroxyl groups promotes the mineralization
      of osteoblast and human mesenchymal stem cell extracellular matrix.
AB  - Functional groups can control biointerfaces and provide a simple way to make
      therapeutic materials. We recently reported the design and synthesis of
      poly(sebacoyl diglyceride) (PSeD) carrying a free hydroxyl group in its repeating
      unit. This paper examines the use of this polymer to promote biomineralization
      for application in bone tissue engineering. PSeD promoted more mineralization of
      extracellular matrix secreted by human mesenchymal stem cells and rat osteoblasts
      than poly(lactic-co-glycolic acid) (PLGA), which is currently widely used in bone
      tissue engineering. PSeD showed in vitro osteocompatibility and in vivo
      biocompatibility that matched or surpassed that of PLGA, as well as supported the
      attachment, proliferation and differentiation of rat osteoblasts and human
      mesenchymal stem cells. This demonstrates the potential of PSeD for use in bone
      regeneration.

PMID- 24560797
TI  - Disease-causing mutations associated with four bestrophinopathies exhibit
      disparate effects on the localization, but not the oligomerization, of Bestrophin
      1.
AB  - BEST1 encodes Bestrophin-1 (Best1), a homo-oligomeric, integral membrane protein
      localized to the basolateral plasma membrane of the retinal pigment epithelium.
      Mutations in BEST1 cause five distinct retinal degenerative diseases, including
      adult vitelliform macular dystrophy (AVMD), autosomal recessive bestrophinopathy
      (ARB), autosomal dominant vitreoretinochoroidopathy (ADVIRC), and retinitis
      pigmentosa (RP). The mechanisms underlying these diseases and why mutations cause
      one disease over another are, for the most part, unknown. To gain insights into
      these four diseases, we expressed 28 Best1 mutants fused to YFP in polarized MDCK
      monolayers and, via confocal microscopy and immunofluorescence, live-cell FRET,
      and reciprocal co-immunoprecipitation experiments, screened these mutants for
      defects in localization and oligomerization. All 28 mutants exhibited comparable
      FRET efficiencies to and co-immunoprecipitated with WT Best1, indicating
      unimpaired oligomerization. RP- and ADVIRC-associated mutants were properly
      localized to the basolateral plasma membrane of cells, while two AVMD and most
      ARB mutants were mislocalized. When co-expressed, all mislocalized mutants caused
      mislocalization of WT Best1 to intracellular compartments. Our current and past
      results indicate that mislocalization of Best1 is not an absolute feature of any
      individual bestrophinopathy, occurring in AVMD, BVMD, and ARB. Furthermore, some
      ARB mutants that do not also cause dominant disease cause mislocalization of
      Best1, indicating that mislocalization is not a cause of disease, and that
      absence of Best1 activity from the plasma membrane is tolerated. Lastly, we find
      that the ARB truncation mutants L174Qfs*57 and R200X can form oligomers with WT
      Best1, indicating that the first ~174 amino acids of Best1 are sufficient for
      oligomerization to occur. 

PMID- 24560800
TI  - Superior epigastric artery perforator flap for sternal osteomyelitis defect
      reconstruction.
AB  - Sternal osteomyelitis after median sternotomy is associated with considerable
      morbidity and mortality. Combined with radical debridement, muscle and less
      frequently omentum flaps are used to reconstruct the resulting defects. In this
      study, we present our experience with the fasciocutaneous superior epigastric
      artery perforator (SEAP) flap for defect closure. After resection of the entire
      sternum, including the costochondral arches and the sternoclavicular joints, the
      repair of the defect was performed with the perforator flap without any re
      stabilisation of the thoracic wall. A consecutive series of nine patients with a
      mean age of 69 +/- 6 years were reconstructed with the SEAP flap. The mortality
      rate was zero. One patient developed a mediastinal haematoma and required five re
      interventions by the cardiothoracic surgeons and thereafter a revision to close a
      small-wound dehiscence at the tip of the flap. Another two patients developed
      partial necrosis of the flap that could be managed conservatively. One patient
      had a revision for a seroma on the donor site, resulting in a 100% closure rate
      of the defect; there were revisions in two out of nine patients. The underlying
      infection was controlled by debridement, antibiotic therapy and flap closure in
      all cases. The overall success of the procedure was satisfactory; however, the
      local complication rate was relatively high with three out of nine patients on
      the flap side and one of nine on the donor site. Major advantages of the
      perforator flap in this highly morbid patient cohort are that the operation is
      relatively quick, muscle tissue is spared and re-education facilitated.

PMID- 24560801
TI  - The clinical applications of human amnion in plastic surgery.
AB  - Since the early 1900s, human amnion has been applied to a wide variety of
      clinical scenarios including burns, chronic ulcers, dural defects, intra
      abdominal adhesions, peritoneal reconstruction, genital reconstruction, hip
      arthroplasty, tendon repair, nerve repair, microvascular reconstruction, corneal
      repair, intra-oral reconstruction and reconstruction of the nasal lining and
      tympanic membrane. Amnion epithelial and mesenchymal cells have been shown to
      contain a variety of regulatory mediators that result in the promotion of
      cellular proliferation, differentiation and epithelialisation and the inhibition
      of fibrosis, immune rejection, inflammation and bacterial invasion. The full
      repertoire of biological factors that these cells synthesise, store and release
      and the mechanisms by which these factors exert their beneficial effects are only
      now being fully appreciated. Although many commercially available biological and
      synthetic alternatives to amnion exist, ethical, religious, and financial
      constraints may limit the widespread utilisation of these products. Amnion is
      widely available, economical and is easy to manipulate, process and store.
      Although many clinical applications are of historical interest only, amnion
      offers an alternative source of multi-potent or pluripotent stem cells and
      therefore may yet have a great deal to offer the plastic surgery and regenerative
      medicine community. It is the purpose of this article to review the clinical
      applications of human amnion relevant to plastic surgery. 

PMID- 24560802
TI  - A 20-year study of persistence of lower urinary tract symptoms and urinary
      incontinence in young women treated in childhood.
AB  - OBJECTIVE: To determine whether urinary incontinence (UI) and lower urinary tract
      symptoms (LUTS) persist over years, patients treated for UI and LUTS in childhood
      were re-evaluated in adulthood. MATERIALS AND METHODS: Forty-seven women (cases)
      treated in childhood for daytime UI/LUTS (group A) and nocturnal enuresis (group
      B) self-completed (average age: 24.89 +/- 3.5 years) the International
      Consultation on Incontinence Questionnaire for Female with LUTS (ICIQ-FLUTS).
      ICIQ-FLUTS was self-administered to 111 healthy women (average age: 23 +/- 5.1
      years) from a nursing school as a control group. Data obtained from ICIQ-FLUTS
      and quality of life (QoL) score (0-10) were compared (Fisher's exact test)
      between patients and controls, and between group A (n = 28) and group B (n = 19).
      RESULTS: Prevalence of LUTS was higher in patients than in controls. The
      difference between patients and controls was statistically significant (p =
      0.0001) for UI (34% vs. 7%) and feeling of incomplete bladder emptying (49% vs.
      28%). QoL score was >5 in 59% of patients and 1% of controls (p = 0.0001). No
      significant differences were found between groups A and B. CONCLUSIONS: UI and
      LUTS are confirmed in young women who suffered for the same condition in
      childhood. Longitudinal studies are needed to assess if these symptoms persist or
      are newly onset.

PMID- 24560803
TI  - Geometric properties and comparative biomechanics of Homo floresiensis mandibles.
AB  - The hypodigm of Homo floresiensis from the cave of Liang Bua on Flores Island in
      the archipelago of Indonesia includes two mandibles (LB1/2 and LB6/1). The
      morphology of their symphyses and corpora has been described as sharing
      similarities with both australopiths and early Homo despite their Late
      Pleistocene age. Although detailed morphological comparisons of these mandibles
      with those of modern and fossil hominin taxa have been made, a functional
      analysis in the context of masticatory biomechanics has yet to be performed.
      Utilizing data on cortical bone geometry from computed tomography scans, we
      compare the mechanical attributes of the LB1 and LB6 mandibles with samples of
      modern Homo, Pan, Pongo, and Gorilla, as well as fossil samples of Paranthropus
      robustus, Australopithecus africanus and South African early Homo. Structural
      stiffness measures were derived from the geometric data to provide relative
      measures of mandibular corpus strength under hypothesized masticatory loading
      regimes. These mechanical variables were evaluated relative to bone area,
      mandibular length and estimates of body size to assess their functional
      affinities and to test the hypothesis that the Liang Bua mandibles can be
      described as scaled-down variants of either early hominins or modern humans.
      Relative to modern hominoids, the H. floresiensis material appears to be
      relatively strong in terms of rigidity in torsion and transverse bending, but is
      relatively weak under parasagittal bending. Thus, they are 'robust' relative to
      modern humans (and comparable with australopiths) under some loads but not
      others. Neither LB1 nor LB6 can be described simply as 'miniaturized' versions of
      modern human jaws since mandible length is more or less equivalent in Homo
      sapiens and H. floresiensis. The mechanical attributes of the Liang Bua mandibles
      are consistent with previous inferences that masticatory loads were reduced
      relative to australopiths but remained elevated relative to modern Homo. 

PMID- 24560805
TI  - Evaluating prion models based on comprehensive mutation data of mouse PrP.
AB  - The structural details of the essential entity of prion disease, fibril prion
      protein (PrP(Sc)), are still elusive despite the large body of evidence
      supporting the prion hypothesis. Five major working models of PrP(Sc) structure,
      which are not compatible with each other, have been proposed. However, no
      systematic evaluation has been performed on those models. We devised a method
      that combined systematic point mutation with threading on knowledge-based amino
      acid potentials. A comprehensive mutation experiment was performed on mouse prion
      protein, and the PrP(Sc) conversion efficiency of each mutant was examined. The
      models were evaluated based on the mutation data by using the threading method.
      Although the data turned out to be rather more consistent with the models that
      assumed a conversion of the N-terminal region of core PrP into a beta helix than
      with others, substantial modifications were also required to further improve the
      current model based on recent experimental results. 

PMID- 24560804
TI  - Nitric oxide-induced conformational changes in soluble guanylate cyclase.
AB  - Soluble guanylate cyclase (sGC) is the primary mediator of nitric oxide (NO)
      signaling. NO binds the sGC heme cofactor stimulating synthesis of the second
      messenger cyclic-GMP (cGMP). As the central hub of NO/cGMP signaling pathways,
      sGC is important in diverse physiological processes such as vasodilation and
      neurotransmission. Nevertheless, the mechanisms underlying NO-induced cyclase
      activation in sGC remain unclear. Here, hydrogen/deuterium exchange mass
      spectrometry (HDX-MS) was employed to probe the NO-induced conformational changes
      of sGC. HDX-MS revealed NO-induced effects in several discrete regions. NO
      binding to the heme-NO/O2-binding (H-NOX) domain perturbs a signaling surface
      implicated in Per/Arnt/Sim (PAS) domain interactions. Furthermore, NO elicits
      striking conformational changes in the junction between the PAS and helical
      domains that propagate as perturbations throughout the adjoining helices.
      Ultimately, NO binding stimulates the catalytic domain by contracting the active
      site pocket. Together, these conformational changes delineate an allosteric
      pathway linking NO binding to activation of the catalytic domain. 

PMID- 24560807
TI  - First report of plasmid-mediated fluoroquinolone efflux pump QepA in Escherichia
      coli clinical isolate ST68, in South America.
AB  - This is the first report of the presence of qepA1 efflux pump gene in Escherichia
      coli clinical isolate from Argentina, which was associated to other plasmid
      mediated quinolone resistance determinants, such as aac(6')-Ib-cr and qnrB10 and
      also quinolone resistance determining regions mutations. 

PMID- 24560806
TI  - High-affinity gold nanoparticle pin to label and localize histidine-tagged
      protein in macromolecular assemblies.
AB  - There is significant demand for experimental approaches to aid protein
      localization in electron microscopy micrographs and ultimately in three
      dimensional reconstructions of macromolecular assemblies. We report preparation
      and use of a reagent consisting of tris-nitrilotriacetic acid (tris-NTA)
      conjugated with a monofunctional gold nanoparticle ((AuNP)tris-NTA) for site
      specific, non-covalent labeling of protein termini fused to a histidine-tag (His
      tag). Multivalent binding of tris-NTA to a His-tag via complexed Ni(II) ions
      results in subnanomolar affinity and a defined 1:1 stoichiometry. Precise
      localization of (AuNP)tris-NTA labeled proteins by electron microscopy is further
      ensured by the reagent's short conformationally restricted linker. We used
      (AuNP)tris-NTA to localize His-tagged proteins in an oligomeric ATPase and in the
      bacterial 50S ribosomal subunit. (AuNP)tris-NTA can specifically bind to the
      target proteins in these assemblies and is clearly discernible. Our labeling
      reagent should find broad application in noncovalent, site-specific labeling of
      protein termini to pinpoint their location in macromolecular assemblies. 

PMID- 24560808
TI  - Concordance of nasal and diabetic foot ulcer staphylococcal colonization.
AB  - Nasal carriage of Staphylococcus aureus (SA) is an important risk factor for
      surgical site infections. The goal of this study was to investigate the
      concordance between nasal and diabetic foot ulcer (DFU) SA carriage. Seventy-nine
      subjects with DFUs were assessed for nasal and DFU colonization with SA,
      including methicillin-resistant SA (MRSA). Twenty-five (31.6%) subjects had nares
      colonization with SA; 29 (36.7%) had DFU colonization with SA. Seven (8.8%)
      subjects had nares colonization with MRSA, and 7 (8.8%) had DFU colonization with
      MRSA. Ulcer duration was associated with MRSA presence (P = 0.01). Sensitivity
      and specificity of positive nasal SA colonization with positive DFU colonization
      were 41% and 74%. We found substantial discordance between SA strains colonizing
      DFU and the nasal cavity. The poor positive predictive values for SA isolation in
      a DFU based on nasal carriage suggests that SA colonization of a DFU by
      endogenous SA strains cannot be assumed. 

PMID- 24560809
TI  - GP73, a new marker for diagnosing HBV-ACLF in population with chronic HBV
      infections.
AB  - Although Golgi protein 73 (GP73) has been widely evaluated for diagnosing
      hepatocellular carcinoma (HCC) and other liver diseases in recent decade, its
      serum profile of patients with hepatitis B virus (HBV)-associated acute-on
      chronic liver failure (HBV-ACLF) is still unknown. This study was designed to
      evaluate the serum levels of GP73 in patients with HBV-ACLF. The participants
      included 200 apparently healthy controls; 200 patients with chronic hepatitis B
      (CHB); 200 patients with HCC; 210 patients with HBV-ACLF, in which 29 HBV-ACLF
      patients were followed up for 3 months. All patients were Hepatitis B virus
      surface antigen (HBsAg) positive. The concentrations of GP73 in patients with HBV
      ACLF (285.3 +/- 128.5 ng/mL) were markedly higher than those HCC patients (159.1
      +/- 105.8 ng/mL), CHB patients (64.65 +/- 44.99 ng/mL), and healthy controls
      (35.37 +/- 12.41 ng/mL). When the cut-off value was set at 182.1 ng/mL, the
      sensitivity and specificity of HBV-ACLF diagnosis were 77.62% (95% confidence
      interval [CI]: 71.37%-83.07%) and 95.50% (95% CI: 92.27%-98.26%), respectively.
      If serum GP73 concentration was still above 361.6 ng/mL after 14 days of follow
      up, the patient's prognosis may be depressed. Serum GP73 may be used to diagnosis
      HBV-ACLF in population with chronic HBV infections. 

PMID- 24560810
TI  - Preservation of cochlear function in Fabp3 (H-Fabp) knockout mice.
AB  - Fatty acid-binding protein 3 (Fabp3) is an intracellular lipid trafficking
      protein that mediates energy metabolism and long-chain fatty acid-related
      signaling. Fabp3 is expressed in the spiral ganglion neurons and supporting cells
      of the organ of Corti. However, it is unclear what role Fabp3 plays in the
      cochlea. Here, we demonstrated that the ABR thresholds of young and aged Fabp3
      knockout mice were unchanged compared with those of wild-type mice. Compared with
      the wild-type mice, the adult mutant mice demonstrated no differences in their
      vulnerability to acoustic overexposure. These results suggest that Fabp3
      deficiency alone does not adversely affect hearing function. 

PMID- 24560812
TI  - Disentangling the low-energy states of the major light-harvesting complex of
      plants and their role in photoprotection.
AB  - The ability to dissipate large fractions of their absorbed light energy as heat
      is a vital photoprotective function of the peripheral light-harvesting pigment
      protein complexes in photosystem II of plants. The major component of this
      process, known as qE, is characterised by the appearance of low-energy (red
      shifted) absorption and fluorescence bands. Although the appearance of these red
      states has been established, the molecular mechanism, their site and particularly
      their involvement in qE are strongly debated. Here, room-temperature single
      molecule fluorescence spectroscopy was used to study the red emission states of
      the major plant light-harvesting complex (LHCII) in different environments, in
      particular conditions mimicking qE. It was found that most states correspond to
      peak emission at around 700nm and are unrelated to energy dissipative states,
      though their frequency of occurrence increased under conditions that mimicked qE.
      Longer-wavelength emission appeared to be directly related to energy dissipative
      states, in particular emission beyond 770nm. The ensemble average of the red
      emission bands shares many properties with those obtained from previous bulk in
      vitro and in vivo studies. We propose the existence of at least three excitation
      energy dissipating mechanisms in LHCII, each of which is associated with a
      different spectral signature and whose contribution to qE is determined by
      environmental control of protein conformational disorder. Emission at 700nm is
      attributed to a conformational change in the Lut 2 domain, which is facilitated
      by the conformational change associated with the primary quenching mechanism
      involving Lut 1. 

PMID- 24560813
TI  - Excitation energy transfer and electron-vibrational coupling in phycobiliproteins
      of the cyanobacterium Acaryochloris marina investigated by site-selective
      spectroscopy.
AB  - In adaption to its specific environmental conditions, the cyanobacterium
      Acaryochloris marina developed two different types of light-harvesting complexes:
      chlorophyll-d-containing membrane-intrinsic complexes and phycocyanobilin (PCB) -
      containing phycobiliprotein (PBP) complexes. The latter complexes are believed to
      form a rod-shaped structure comprising three homo-hexamers of phycocyanin (PC),
      one hetero-hexamer of phycocyanin and allophycocyanin (APC) and probably a linker
      protein connecting the PBPs to the reaction centre. Excitation energy transfer
      and electron-vibrational coupling in PBPs have been investigated by selectively
      excited fluorescence spectra. The data reveal a rich spectral substructure with a
      total of five low-energy electronic states with fluorescence bands at 635nm,
      645nm, 654nm, 659nm and a terminal emitter at about 673 nm. The electronic states
      at ~635 and 645 nm are tentatively attributed to PC and APC, respectively, while
      an apparent heterogeneity among PC subunits may also play a role. The other
      fluorescence bands may be associated with three different isoforms of the linker
      protein. Furthermore, a large number of vibrational features can be identified
      for each electronic state with intense phonon sidebands peaking at about 31 to
      37cm-1, which are among the highest phonon frequencies observed for
      photosynthetic antenna complexes. The corresponding Huang-Rhys factors S fall in
      the range between 0.98 (terminal emitter), 1.15 (APC), and 1.42 (PC). Two
      characteristic vibronic lines at about 1580 and 1634cm-1 appear to reflect CNH+
      and CC stretching modes of the PCB chromophore, respectively. The exact phonon
      and vibrational frequencies vary with electronic state implying that the
      respective PCB chromophores are bound to different protein environments. This
      article is part of a special issue entitled: photosynthesis research for
      sustainability: keys to produce clean energy.

PMID- 24560811
TI  - ND3, ND1 and 39kDa subunits are more exposed in the de-active form of bovine
      mitochondrial complex I.
AB  - An intriguing feature of mitochondrial complex I from several species is the so
      called A/D transition, whereby the idle enzyme spontaneously converts from the
      active (A) form to the de-active (D) form. The A/D transition plays an important
      role in tissue response to the lack of oxygen and hypoxic deactivation of the
      enzyme is one of the key regulatory events that occur in mitochondria during
      ischaemia. We demonstrate for the first time that the A/D conformational change
      of complex I does not affect the macromolecular organisation of supercomplexes in
      vitro as revealed by two types of native electrophoresis. Cysteine 39 of the
      mitochondrially-encoded ND3 subunit is known to become exposed upon de
      activation. Here we show that even if complex I is a constituent of the I+III2+IV
      (S1) supercomplex, cysteine 39 is accessible for chemical modification in only
      the D-form. Using lysine-specific fluorescent labelling and a DIGE-like approach
      we further identified two new subunits involved in structural rearrangements
      during the A/D transition: ND1 (MT-ND1) and 39kDa (NDUFA9). These results clearly
      show that structural rearrangements during de-activation of complex I include
      several subunits located at the junction between hydrophilic and hydrophobic
      domains, in the region of the quinone binding site. De-activation of
      mitochondrial complex I results in concerted structural rearrangement of membrane
      subunits which leads to the disruption of the sealed quinone chamber required for
      catalytic turnover. 

PMID- 24560814
TI  - Modular pathway engineering of Bacillus subtilis for improved N-acetylglucosamine
      production.
AB  - In previous work, we constructed a recombinant Bacillus subtilis strain for
      microbial production of N-acetylglucosamine (GlcNAc), which has applications in
      nutraceuticals and pharmaceuticals. In this work, we improve GlcNAc production
      through modular engineering of B. subtilis. Specifically, the GlcNAc synthesis
      related metabolic network in B. subtilis was divided into three modules-GlcNAc
      synthesis, glycolysis, and peptidoglycan synthesis. First, two-promoter systems
      with different promoter types and strengths were used for combinatorial assembly
      of expression cassettes of glmS (encoding GlcN-6-phosphate synthase) and GNA1
      (encoding GlcNAc-6-phosphate N-acetyltransferase) at transcriptional levels in
      the GlcNAc synthesis module, resulting in a 32.4% increase in GlcNAc titer (from
      1.85g/L to 2.45g/L) in shake flasks. In addition, lactate and acetate synthesis
      were blocked by knockout of ldh (encoding lactate dehydrogenase) and pta
      (encoding phosphotransacetylase), leading to a 44.9% increase in GlcNAc
      production (from 2.45g/L to 3.55g/L) in shake flasks. Then, various strengths of
      the glycolysis and peptidoglycan synthesis modules were constructed by repressing
      the expression of pfk (encoding 6-phosphofructokinase) and glmM (encoding
      phosphoglucosamine mutase) via the expression of various combinations of
      synthetic small regulatory RNAs and Hfq protein. Next, GlcNAc, glycolysis, and
      peptidoglycan synthesis modules with various strengths were assembled and
      optimized via a module engineering approach, and the GlcNAc titer was improved to
      8.30g/L from 3.55g/L in shake flasks. Finally, the GlcNAc titer was further
      increased to 31.65g/L, which was 3.8-fold that in the shake flask, in a 3-L fed
      batch bioreactor. This work significantly enhanced GlcNAc production through
      modular pathway engineering of B. subtilis, and the engineering strategies used
      herein may be useful for the construction of versatile B. subtilis cell factories
      for the production of other industrially important chemicals. 

PMID- 24560815
TI  - Redox-mediated signal transduction by cardiovascular Nox NADPH oxidases.
AB  - The only known function of the Nox family of NADPH oxidases is the production of
      reactive oxygen species (ROS). Some Nox enzymes show high tissue-specific
      expression and the ROS locally produced are required for synthesis of hormones or
      tissue components. In the cardiovascular system, Nox enzymes are low abundant and
      function as redox-modulators. By reacting with thiols, nitric oxide (NO) or trace
      metals, Nox-derived ROS elicit a plethora of cellular responses required for
      physiological growth factor signaling and the induction and adaptation to
      pathological processes. The interactions of Nox-derived ROS with signaling
      elements in the cardiovascular system are highly diverse and will be detailed in
      this article, which is part of a Special Issue entitled "Redox Signalling in the
      Cardiovascular System". 

PMID- 24560816
TI  - Is this the real time for genomics?
AB  - In the last decades, molecular biology has moved from gene-by-gene analysis to
      more complex studies using a genome-wide scale. Thanks to high-throughput genomic
      technologies, such as microarrays and next-generation sequencing, a huge amount
      of information has been generated, expanding our knowledge on the genetic basis
      of various diseases. Although some of this information could be transferred to
      clinical diagnostics, the technologies available are not suitable for this
      purpose. In this review, we will discuss the drawbacks associated with the use of
      traditional DNA microarrays in diagnostics, pointing out emerging platforms that
      could overcome these obstacles and offer a more reproducible, qualitative and
      quantitative multigenic analysis. New miniaturized and automated devices, called
      Lab-on-Chip, begin to integrate PCR and microarray on the same platform, offering
      integrated sample-to-result systems. The introduction of this kind of innovative
      devices may facilitate the transition of genome-based tests into clinical
      routine. 

PMID- 24560817
TI  - Let the games begin (with EAU approval).

PMID- 24560818
TI  - EAU policy on live surgery events.
AB  - CONTEXT: Live surgery is an important part of surgical education, with an
      increase in the number of live surgery events (LSEs) at meetings despite
      controversy about their real educational value, risks to patient safety, and
      conflicts of interest. OBJECTIVE: To provide a European Association of Urology
      (EAU) policy on LSEs to regulate their organisation during urologic meetings.
      EVIDENCE ACQUISITION: The project was carried out in phases: a systematic
      literature review generating key questions, surveys sent to Live Surgery Panel
      members, and Internet- and panel-based consensus finding using the Delphi process
      to agree on and formulate a policy. EVIDENCE SYNTHESIS: The EAU will endorse
      LSEs, provided that the EAU Code of Conduct for live surgery and all
      organisational requirements are followed. Outcome data must be submitted to an
      EAU Web-based registry and complications reported using the revised Martin
      criteria. Regular audits will take place to evaluate compliance as well as the
      educational role of live surgery. CONCLUSIONS: This policy represents the
      consensus view of an expert panel established to advise the EAU. The EAU
      recognises the educational role of live surgery and endorses live case
      demonstration at urologic meetings that are conducted within a clearly defined
      regulatory framework. The overriding principle is that patient safety must take
      priority over all other considerations in the conduct of live surgery. PATIENT
      SUMMARY: Controversy exists regarding the true educational value of live surgical
      demonstrations on patients at surgical meetings. An EAU committee of experts
      developed a policy on how best to conduct live surgery at urologic meetings. The
      key principle is to ensure safety for every patient, including a code of conduct
      and checklist for live surgery, specific rules for how the surgery is organised
      and performed, and how each patient's results are reported to the EAU. For
      detailed information, please visit www.uroweb.org.

PMID- 24560820
TI  - Material modeling of biofilm mechanical properties.
AB  - A biofilm material model and a procedure for numerical integration are developed
      in this article. They enable calculation of a composite Young's modulus that
      varies in the biofilm and evolves with deformation. The biofilm-material model
      makes it possible to introduce a modeling example, produced by the Unified Multi
      Component Cellular Automaton model, into the general-purpose finite-element code
      ABAQUS. Compressive, tensile, and shear loads are imposed, and the way the
      biofilm mechanical properties evolve is assessed. Results show that the local
      values of Young's modulus increase under compressive loading, since compression
      results in the voids "closing," thus making the material stiffer. For the
      opposite reason, biofilm stiffness decreases when tensile loads are imposed.
      Furthermore, the biofilm is more compliant in shear than in compression or
      tension due to the how the elastic shear modulus relates to Young's modulus. 

PMID- 24560821
TI  - Impact of everolimus versus other rapamycin derivative-eluting stents on clinical
      outcomes in patients with coronary artery disease: a meta-analysis of 16
      randomized trials.
AB  - BACKGROUND: Everolimus-eluting stent (EES) are considered to have better clinical
      outcomes than other rapamycin derivative-eluting stents; however, the individual
      trials may not have sufficient power to prove it. This meta-analysis aimed to
      compare clinical outcomes of EES against other rapamycin derivative-eluting
      stents. METHODS: We searched Medline, the Cochrane Library, and other internet
      sources, without language or date restrictions for articles comparing clinical
      outcomes between EES and other rapamycin derivative-eluting stents. Safety
      endpoints were stent thrombosis (ST), mortality, cardiac death, and myocardial
      infarction (MI). Efficacy endpoints were major adverse cardiac events (MACE),
      target lesion revascularization (TLR), and target vessel revascularization (TVR).
      RESULTS: We identified 16 randomized controlled trials with 23,481 patients and a
      weighted mean follow-up of 18 months. Compared with other rapamycin derivative
      eluting stents, EES were associated with a significant reduction in definite ST
      [relative risk (RR): 0.45; 95% confidence interval (CI): 0.30-0.69; p<0.001] and
      TLR (RR: 0.87; 95% CI: 0.77-0.99; p=0.03). EES also showed a non-significant
      trend toward reduction in definite/probable ST (RR: 0.75; 95% CI: 0.56-1.01;
      p=0.06). However, both groups had similar rates of mortality (RR: 0.95; 95% CI:
      0.82-1.09; p=0.45), MI (RR: 0.95; 95% CI: 0.82-1.10; p=0.43), and MACE (RR: 0.94;
      95% CI: 0.87-1.02; p=0.35). The stratified analysis of the included trials showed
      that EES was associated with significantly lower rate of definite ST compared
      with either zotarolimus-eluting stent (p=0.012) or sirolimus-eluting stent
      (p=0.006), but not biolimus-eluting stent (p=0.16). In longer follow-up (>1 year)
      stratification, EES was associated with a significant reduction in risk of
      definite ST (p<0.001). CONCLUSIONS: EES is associated with a significant
      reduction in definite ST and TLR for treating patients with coronary artery
      disease, compared with a pooled group of other rapamycin derivative-eluting
      stents. Biolimus-eluting stent had similar safety and efficacy for treating
      patients with coronary artery disease, compared with the EES.

PMID- 24560822
TI  - Percutaneous endovascular repair of popliteal artery aneurysms.
AB  - BACKGROUND: To evaluate percutaneous endovascular repair of popliteal artery
      aneurysms (PAAs) using self-expanding covered stent grafts. METHODS: A
      retrospective record review of consecutive patients who underwent percutaneous
      endovascular PAA repair across 2 Australian centers between April 2009 and May
      2012 was performed. RESULTS: We report 16 patients (mean age: 77.3; 93% men) with
      PAA in 20 limbs who underwent percutaneous endovascular repair using self
      expanding covered stent grafts. The mean aneurysm diameter was 3 cm (range: 2-5.1
      cm). Ultrasound-guided percutaneous antegrade access was used in all cases: 16
      superficial femoral artery punctures and 4 common femoral artery punctures. The
      mean number of runoff vessels per limb was 1.84 (42%, 1 vessel; 32%, 2 vessels;
      and 26%, 3 vessels). Technical success was 100%. A mean number of 1.82 stents
      were deployed in each limb (range: 1-3). The mean stent diameter was 8.84 (range:
      6-13). The median follow-up time was 12 months (range: 0-24 months). Primary
      patency of 85% and secondary patency of 90% were achieved in our study. The limb
      loss and mortality rate were 5% both in a patient with an undiagnosed
      prothrombotic condition. Puncture site complications were seen in 1 patient (5%)
      who had a bleeding diathesis. CONCLUSIONS: Percutaneous endovascular repair of
      PAA using self-expanding stent grafts can be safely performed and achieved good
      results achieved in most patients.

PMID- 24560823
TI  - Promotion of artery occlusion in dogs by percutaneous rotational atherectomy.
AB  - BACKGROUND: This study aims to offer experimental data and indirect evidences for
      the application of percutaneous rotational atherectomy to treat patent ductus
      arteriosus (PDA). METHODS: Eleven dogs (6 male dogs and 5 female dogs; aged 14-20
      months, with an average of 16.7+/-3.2 months; weight 20-25 kg, with an average of
      22.7+/-2.5 kg) were enrolled in this study. The diameters of the left and right
      arteries ranged from 3.2 to 4.8 mm (average 3.9+/-0.6 mm) on percutaneous
      angiography. Percutaneous rotational atherectomy with proper rotablator (the size
      was 1-1.5 mm larger than the artery diameter) was performed in the arterial
      intima. After 4 weeks from percutaneous rotational atherectomy, arteriography was
      conducted to observe the changes in artery diameter. Then all dogs were
      sacrificed and the pathologic examination was conducted on the left and right
      axillary arteries. RESULTS: There were obvious changes with different degrees in
      22 arteries, including 8 arteries with complete occlusion and 12 arteries with
      stenosis (>=2/3, 1/2, and 1/3 stenosis in 4, 4, and 4 arteries, respectively).
      The occlusion rate was 36.4% and the total effective rate was 90.9%. It was
      considered failure in other 2 arteries with <1/3 of stenosis. CONCLUSIONS:
      Percutaneous rotational atherectomy of arterial intima can promote the occlusion
      of arteries. This has provided a new choice for the treatment of PDA.

PMID- 24560819
TI  - Sex differences in stroke: the contribution of coagulation.
AB  - Stroke is now the leading cause of adult disability in the United States. Women
      are disproportionately affected by stroke. Women increasingly outnumber men in
      the elderly population, the period of highest risk for stroke. However, there is
      also a growing recognition that fundamental sex differences are present that
      contribute to differential ischemic sensitivity. In addition, gonadal hormone
      exposure can impact coagulation and fibrinolysis, key factors in the initiation
      of thrombosis. In this review we will discuss sex differences in stroke, with a
      focus on platelets, vascular reactivity and coagulation. 

PMID- 24560824
TI  - Factors influencing the attitudes of cattle veterinarians, farmers, and claw
      trimmers towards the pain associated with the treatment of sole ulcers and the
      sensitivity to pain of dairy cows.
AB  - This study assessed the attitudes of personnel involved in therapeutic claw
      trimming of dairy cattle in Switzerland towards pain associated with sole ulcers
      and their treatment. Data from 77 farmers, 32 claw trimmers, and 137 cattle
      veterinarians were used. A large range of factors were associated with whether
      the respondents thought that anaesthesia during the treatment of sole ulcers was
      beneficial; these included year of graduation, work experience, attitude to costs
      of analgesia, perception of competition between veterinarians and claw trimmers,
      estimation of pain level associated with treatment, estimated sensitivity of
      dairy cows to pain, knowledge of the obligation to provide analgesia, and whether
      the respondent thought lesion size and occurrence of defensive behaviour by the
      cow were important. Respondents' estimation of the pain level associated with
      sole ulcer treatment was linked to frequency of therapeutic claw trimming, age,
      farmers' income, estimated knowledge of the benefits of analgesia, and estimated
      sensitivity of dairy cows to pain. The latter factor was associated with
      profession, frequency of therapeutic claw trimming, capability of pain
      recognition, opinion on the benefits of analgesia, knowledge of the obligation to
      provide analgesia, and self-estimation of the ability to recognise pain.
      Improving the knowledge of personnel involved in therapeutic claw trimming with
      regard to pain in dairy cows and how to alleviate it is crucial if management of
      pain associated with treatment of sole ulcer and the welfare of lame cows are to
      be optimised. 

PMID- 24560825
TI  - Documentation of resuscitation decision-making: a survey of practice in the
      United Kingdom.
AB  - Do Not Attempt Cardiopulmonary Resuscitation (DNACPR) orders have been in use
      since the 1990s. The Resuscitation Council UK (RCUK) provides guidance on the
      content and use of such forms in the UK but there is no national policy. AIM: To
      determine the content of DNACPR forms in the UK, and the geographical
      distribution of the use of different forms. METHODS: All acute trusts within the
      United Kingdom were contacted via a combination of email and telephone, with a
      request for the current DNACPR form along with information about its development
      and use. Characteristics of the model RCUK DNACPR form were compared with the non
      RCUK DNACPR forms which we received. Free text responses were searched for
      commonly occurring phrases. RESULTS: 118/161 English NHS Acute Trusts (accounting
      for 377 hospitals), 3/6 Northern Irish NHS Acute Trusts (accounting for 25
      hospitals) and 3/7 Welsh Health Boards (accounting for 73 hospitals) responded.
      All Scottish hospitals have the same form. All responding trusts had active
      policies and have a DNACPR form in use. 38.9% of respondent hospitals have
      adopted the RCUK form with minor amendments. The remainder of the responding
      hospitals reported independent forms. 66.8% of non-RCUK forms include a transfer
      plan to ambulance staff and 48.4% of non-RCUK forms are valid in the community.
      Several independent trusts submitted DNACPR forms with escalation plans.
      CONCLUSIONS: There is wide variation in the forms used for indicating DNACPR
      decisions. Documentation is rapidly evolving to meet the needs of patients and to
      respond to new evidence.

PMID- 24560826
TI  - Therapeutic hypothermia: focus on microcirculation.

PMID- 24560827
TI  - The psychosocial outcomes of anoxic brain injury following cardiac arrest.
AB  - AIM OF THE STUDY: This exploratory study aimed to investigate the psychosocial
      outcomes for cardiac arrest survivors and explore if there is a greater impact on
      psychosocial outcome for individuals experiencing anoxic brain injury as a result
      of the cardiac arrest. METHODS: Self-report measures were used to compare the
      quality of life, social functioning and symptoms of anxiety, depression and post
      traumatic stress of individuals with and without anoxic brain injury. Secondary
      measures of subjective memory and executive difficulties were also used. Fifty
      six participants (27 with anoxia, 29 without anoxia) took part in the study
      between six months and four years after experiencing cardiac arrest. RESULTS: A
      MANOVA identified a significant difference between the two groups, with the
      anoxia group reporting more psychosocial difficulties. They reported more social
      functioning difficulties and more anxiety, depression and post-traumatic stress
      symptoms. There was, however, no significant difference in self-reported quality
      of life between the two groups. CONCLUSION: As the first known study to compare
      psychosocial outcomes for cardiac arrest survivors experiencing anoxic brain
      injury with those without anoxia, the current results suggest that cardiac arrest
      survivors with subsequent acquired brain injury experience more psychosocial
      difficulties. This could be due to a combination of neuropsychological, social
      and psychological factors.

PMID- 24560828
TI  - Cardiac arrest due to drowning--changes over time and factors of importance for
      survival.
AB  - AIM: To evaluate changes in characteristics and survival over time in out-of
      hospital cardiac arrest (OHCA) due to drowning and describe factors of importance
      for survival. METHOD: Retrospectively reported and treated drowning cases
      reported to the Swedish OHCA registry between 1990 and 2012, n=529. The data were
      clustered into three seven-year intervals for comparisons of changes over time.
      RESULTS: There were no changes in age, gender, witnessed status, shockable rhythm
      or place of OHCA during the time periods. Bystander CPR increased over time, 59%
      in interval 1992-1998, versus 74% in interval 2006-2012 (p=0.005). There was a
      decrease in delay between OHCA and calling for the Emergency Medical Service
      (EMS) over the years, while calling for the EMS to arrival increased in terms of
      time. Survival to hospital admission appears to have increased over the years
      (p=0.009), whereas survival to one month did not change significantly over time.
      In a multivariate analysis, witnessed status, female gender, bystander CPR, place
      home and EMS response time were associated with survival to hospital admission.
      For survival to one month, place, age, shockable rhythm and logarithmised delay
      from calling for an ambulance to arrival were of significance for survival.
      CONCLUSION: In OHCA due to drowning, over a period of 20 years, bystanders have
      called for help at an earlier stage and administered CPR more frequently in the
      past few years. Survival to hospital admission has increased, while shockable
      rhythm and early arrival of the EMS appear to be the most important factors for
      survival to one month.

PMID- 24560830
TI  - First report of blaNDM-1-producing Acinetobacter baumannii isolated in Lebanon
      from civilians wounded during the Syrian war.
AB  - OBJECTIVES: The emergence of carbapenem-resistant Acinetobacter baumannii has
      been observed worldwide. We describe the first detection of A. baumannii carrying
      the blaNDM-1 gene in Lebanon, isolated from Syrian patients wounded during the
      civil war. METHODS: Four carbapenem-resistant A. baumannii strains isolated in
      2012 in the Tripoli Government Hospital, Lebanon, from civilians wounded during
      the Syrian war, were analysed. Susceptibility was determined by disk diffusion
      testing, and resistance to carbapenems was confirmed by Etest. The presence of
      blaOXA-23-like, blaOXA-24-like, blaOXA-58-like, blaOXA-143-like, and blaNDM was
      investigated by PCR. Clonal relationships were studied by pulsed-field gel
      electrophoresis (PFGE), multilocus sequence typing (MLST), and blaOXA-51 sequence
      based typing. RESULTS: All isolates harboured the blaNDM-1 gene and were negative
      for other tested carbapenemases. They all belonged to the sequence type 85 and
      formed a single cluster by PFGE. Finally, blaOXA-51-like gene sequencing revealed
      the presence of the blaOXA-94 variant in all four isolates. CONCLUSION: These
      findings show that Syria constitutes a reservoir for NDM-1-producing bacteria.
      These results also highlight the need for effective measures to stop the
      threatening spread of such strains.

PMID- 24560831
TI  - Pseudomonas aeruginosa ecthyma gangrenosum in a woman with recurrent Graves'
      disease.
AB  - A 35-year-old woman with postoperative recurrent Graves' disease presented with a
      5-day history of a red swelling on the right cheek associated with 4 days of
      remittent hyperpyrexia. Investigations revealed fever, a gangrenous ulcer on the
      right cheek, submandibular lymphadenopathy, and thyroid gland enlargement. Her
      white blood cell count, immunoglobulins, and lymphocyte subsets were
      unremarkable. Thyroid function tests showed low thyroid-stimulating hormone, high
      free thyroxine, and elevated radioactive iodine uptake. Repeated pus cultures
      grew Pseudomonas aeruginosa, but blood cultures were negative. An ill-demarcated
      erythematous plaque occurred on the right leg on hospital day 3. She was treated
      with intravenous antibiotics with topical gentamicin, recombinant bovine basic
      fibroblast growth factor, and radioiodine therapy with anti-thyroid drugs. The
      ulcer healed leaving a depressed scar at 35 days after discharge. This patient
      may represent the first case of P. aeruginosa ecthyma gangrenosum and cellulitis
      in postoperative recurrent Graves' disease. 

PMID- 24560832
TI  - Making the in vitro breeding of Schistocephalus solidus more flexible.
AB  - Schistocephalus solidus is one of the few cestodes that can be bred in vitro.
      Worms have typically been bred in pairs, so the parents of each offspring can
      clearly be assigned. From a genetic perspective, it would be useful to be able to
      mate an individual worm to multiple partners while still being able to
      distinguish among different parents. As each adult S. solidus possesses numerous
      reproductive complexes, cutting worms and breeding the pieces separately would
      facilitate such breeding designs. We halved worms before in vitro breeding and
      evaluated whether this affected outcrossing rates and reproductive output.
      Cutting did not influence clutch mass, i.e. egg number and size, or outcrossing
      rates, but eggs from cut worms had a lower hatching rate than eggs from uncut
      worms. We found that when two anterior worm halves were bred together, they
      produced fewer, smaller eggs with higher hatching rates, compared to two
      posterior halves. Moreover, once we controlled for this effect of 'worm half',
      the two halves of an individual worm tended to reproduce similarly under
      comparable circumstances. We conclude that cutting plerocercoids increases the
      flexibility with which this tapeworm can be experimentally bred without
      dramatically affecting the production of viable, outcrossed eggs. 

PMID- 24560833
TI  - Evaluation of the use of C-terminal part of the Schistosoma mansoni 200kDa
      tegumental protein in schistosomiasis diagnosis and vaccine formulation.
AB  - Schistosoma mansoni tegument is involved in essential functions for parasite
      survival and represents a target for screening candidates for vaccine and
      diagnosis. Our group using reverse vaccinology selected six candidates,
      previously demonstrated by proteomics studies to be expressed in the parasite
      tegument, among them was Sm200. In this work we have cloned and expressed a
      recombinant form of Sm200 C-terminal (1069-1520) region. The efficacy of rSm200
      (1069-1520) in the diagnosis of schistosomiasis and in the formulation of a
      vaccine against S. mansoni was assessed respectively in an ELISA based diagnostic
      assay and immunization protocols in mice. Significant differences between non
      infected and acutely infected or chronically infected animals were observed and
      no cross-recognition was observed with sera from Ascaris suum or Ancylostoma
      ceylanicum infected mice. rSm200-ELISA test could also discriminate infected
      individuals from healthy donors not living in endemic area for schistosomiasis
      but failed to discriminate between individuals from a low endemic area for
      schistosomiasis known to have positive or negative stools after examination.
      Recombinant Sm200 also failed to induce protection against schistosomiasis,
      demonstrating that the C-terminal part of Sm200 is unable to induce protective
      immune response in mice. Therefore rSm200 (1069-1520)-ELISA represents an
      important tool to be used in the diagnosis of schistosomiasis. 

PMID- 24560834
TI  - Prevalence and treatment of pain in EDs in the United States, 2000 to 2010.
AB  - OBJECTIVES: To describe changes in the prevalence and severity of pain and
      prescribing of non-opioid analgesics in US emergency departments (EDs) from 2000
      to 2010. METHODS: Analysis of serial cross-sectional data regarding ED visits
      from the National Hospital Ambulatory Medical Care Survey. Visits were limited to
      patients >=18 years old without malignancy. Outcome measures included annual
      volume of visits among adults with a primary symptom or diagnosis of pain, annual
      rates of patient-reported pain severity, and predictors of non-opioid receipt for
      non-malignant pain. RESULTS: Rates of pain remained stable, representing
      approximately 45% of visits from 2000 through 2010. Patients reported pain as
      their primary symptom twice as often as providers reported a primary pain
      diagnosis (40% vs 20%). The percentage of patients reporting severe pain
      increased from 25% (95% confidence intervals [CI] 22%-27%) in 2003 to 40% (CI 37%
      42%) in 2008. From 2000 to 2010, the proportion of pain visits treated with
      pharmacotherapies increased from 56% (CI 53%-58%) to 71% (CI 69%-72%), although
      visits treated exclusively with non-opioids decreased 21% from 28% (CI 27%-30%)
      to 22% (CI 20%-23%). The adjusted odds of non-opioid rather than opioid receipt
      were greater among visits for patients 18 to 24 years old (odds ratio [OR] 1.35,
      CI 1.24-1.46), receiving fewer medicines (OR 2.91, CI 2.70-3.15) and those with a
      diagnosis of mental illness (OR 2.24, CI 1.99-2.52). CONCLUSIONS: Large increases
      in opioid utilization in EDs have coincided with reductions in the use of non
      opioid analgesics and an unchanging prevalence of pain among patients.

PMID- 24560835
TI  - The accuracy of mainstream end-tidal carbon dioxide levels to predict the
      severity of chronic obstructive pulmonary disease exacerbations presented to the
      ED.
AB  - INTRODUCTION: The end-tidal carbon dioxide (ETCO2) measurement was considered as
      an essential tool for the assessment of several conditions in emergency medicine.
      However, the diagnostic role of capnography in dyspneic patients still remains
      unclear. We aimed to analyze the alteration of the ETCO2 levels in chronic
      obstructive pulmonary disease (COPD) exacerbations and its role in the decision
      making process. METHODS: All the individuals who were presented to the emergency
      department (ED) after COPD exacerbations were prospectively enrolled in the
      study. The patients were excluded if they refused to give informed consent,
      intubated after initial assessment, and had uncertain COPD diagnosis. The ETCO2
      measurement using a mainstream capnometer was undertaken in the pretreatment and
      post-treatment period of COPD exacerbations. RESULTS: A total of 102 patients
      were enrolled in the study. Pre-ETCO2 and post-ETCO2 levels were positively
      correlated with arterial partial carbon dioxide pressure levels (r=0.756, P<.001
      and r=0.629, P<.001, respectively). The median pre-ETCO2 level was 32.0 (30.5
      40.5) in discharged patients and 39.0 (31.0-53.5) in admitted patients. After the
      initial therapy in the ED was completed, the median post-ETCO2 level was found to
      be 32.0 (28.0-37.5) in discharged patients and 36.0 (32.0-52.0) in admitted
      patients. Although a statistically significant difference was observed in the
      pretreatment period (P=.043), no difference was observed in post-treatment period
      between ETCO2 levels (P=.107). CONCLUSION: End-tidal carbon dioxide levels were
      higher in admitted patients when compared with discharged patients on arrival to
      the ED. ETCO2 measurement has very little contributions while evaluating patients
      with COPD exacerbation in the ED.

PMID- 24560836
TI  - Endoscopic treatment of a symptomatic gastric mucosal bridge.

PMID- 24560837
TI  - Work-related musculoskeletal disorders in veterinary echocardiographers: a cross
      sectional study on prevalence and risk factors.
AB  - OBJECTIVE: Assess the relationship between work-related musculoskeletal disorders
      (WRMSDs) and performing echocardiograms (ECHOS) in veterinarians with a
      cardiology focus. METHODS: Prospective study. A survey was submitted to the ACVIM
      veterinary cardiology list-serve regarding pain associated with performing ECHOS
      (ECHOPain). Associations of demographic and work habit variables with ECHOPain
      and WRMSD were evaluated with logistic regression. RESULTS: Respondents included
      198 of 487 (41%) members, evenly divided in gender. Most (69%) were 31-50 years
      old. Almost all (96%) currently perform ECHOS, usually 4-5 ECHOS/week (74%),
      every week except vacation (93%). ECHOPain was reported by 87 people (44%), which
      was classified as mild/occasional in 77%, frequent/moderate in 21%, and
      frequent/severe in 2%. Of those with ECHOPain, 52% reported ECHOS as the sole
      cause, 31% reported ECHOS aggravating pain from a pre-existing problem, and 17%
      reported unrelated pain. The most common areas of pain were neck (54%), shoulder
      (52%), wrist (42%), and back (35%) with 78% reporting pain at 2 or more sites.
      Pain impaired job performance in 36%, required sick leave or disability in 12%,
      required reduction in ECHOS/day in 36%, and affected lifestyle in 22%. Ten
      percent of people have been diagnosed with WRMSD, of which 21% have a permanent
      disability. Both gender and weeks/year predicted pain with ECHOS (chi(2)(3) =
      11.38, P = 0.01). The odds ratio for females versus males with ECHOPain was 2.23.
      CONCLUSION: ECHOPain is common (44%) in veterinary echocardiographers, is
      significantly associated with gender, and affects job performance for over one
      third of pain sufferers.

PMID- 24560838
TI  - The effects of temperature, salinity, concentration and PEGylated lipid on the
      spontaneous nanostructures of bicellar mixtures.
AB  - The self-assembling morphologies of low-concentration (mostly 1 and 10mg/mL)
      bicellar mixtures composed of zwitterionic dipalmitoyl (di-C16)
      phosphatidylcholine (DPPC), dihexanoyl (di-C6) phosphatidylcholine (DHPC), and
      negatively charged dipalmitoyl (di-C16) phosphatidylglycerol (DPPG) were
      investigated using small angle neutron scattering, dynamic light scattering and
      transmission electron microscopy. A polyethylene glycol conjugated (PEGylated)
      lipid, distearoyl phosphoethanolamine-[methoxy (polyethyleneglycol)-2000]
      (PEG2000-DSPE), was incorporated in the system at 5mol% of the total lipid
      composition. The effects of several parameters on the spontaneous structures were
      studied, including temperature, lipid concentration, salinity, and PEG2000-DSPE.
      In general, nanodiscs (bicelles) were observed at low temperatures (below the
      melting temperature, TM of DPPC) depending on the salinity of the solutions.
      Nanodisc-to-vesicle transition was found upon the elevation of temperature (above
      TM) in the cases of low lipid concentration in the absence of PEG2000-DSPE or
      high salinity. Both addition of PEG2000-DSPE and high lipid concentration
      stabilize the nanodiscs, preventing the formation of multilamellar vesicles,
      while high salinity promotes vesiculation and the formation of aggregation. This
      study suggests that the stability of such nanodiscs is presumably controlled by
      the electrostatic interactions, the steric effect induced by PEG2000-DSPE, and
      the amount of DHPC located at the disc rim. 

PMID- 24560839
TI  - Response to Letter: Aneurysm, ischemic stroke and cysticercosis.

PMID- 24560840
TI  - Dopamine signaling in the amygdala, increased by food ingestion and GLP-1,
      regulates feeding behavior.
AB  - Mesolimbic dopamine plays a critical role in food-related reward processing and
      learning. The literature focuses primarily on the nucleus accumbens as the key
      dopaminergic target in which enhanced dopamine signaling is associated with
      reward. Here, we demonstrate a novel neurobiological mechanism by which dopamine
      transmission in the amygdala regulates food intake and reward. We show that food
      intake was associated with increased dopamine turnover in the amygdala. Next, we
      assess the impact of direct intra-amygdala D1 and D2 receptor activation on food
      intake and sucrose-driven progressive ratio operant conditioning in rats.
      Amygdala D2 receptor activation reduced food intake and operant behavior for
      sucrose, whereas D2 receptor blockade increased food intake but surprisingly
      reduced operant behavior. In contrast, D1 receptor stimulation or blockade did
      not alter feeding or operant conditioning for food. The glucagon-like peptide 1
      (GLP-1) system, a target for type 2 diabetes treatment, in addition to regulating
      glucose homeostasis, also reduces food intake. We found that central GLP-1R
      receptor activation is associated with elevated dopamine turnover in the
      amygdala, and that part of the anorexic effect of GLP-1 is mediated by D2
      receptor signaling in the amygdala. Our findings indicate that amygdala dopamine
      signaling is activated by both food intake and the anorexic brain-gut peptide GLP
      1 and that amygdala D2 receptor activation is necessary and sufficient to change
      feeding behavior. Collectively these studies indicate a novel mechanism by which
      the dopamine system affects feeding-oriented behavior at the level of the
      amygdala. 

PMID- 24560841
TI  - Brief, pre-learning stress reduces false memory production and enhances true
      memory selectively in females.
AB  - Some of the previous research on stress-memory interactions has suggested that
      stress increases the production of false memories. However, as accumulating work
      has shown that the effects of stress on learning and memory depend critically on
      the timing of the stressor, we hypothesized that brief stress administered
      immediately before learning would reduce, rather than increase, false memory
      production. In the present study, participants submerged their dominant hand in a
      bath of ice cold water (stress) or sat quietly (no stress) for 3 min. Then,
      participants completed a short-term memory task, the Deese-Roediger-McDermott
      paradigm, in which they were presented with 10 different lists of semantically
      related words (e.g., candy, sour, sugar) and, after each list, were tested for
      their memory of presented words (e.g., candy), non-presented unrelated
      "distractor" words (e.g., hat), and non-presented semantically related "critical
      lure" words (e.g., sweet). Stress, overall, significantly reduced the number of
      critical lures recalled (i.e., false memory) by participants. In addition, stress
      enhanced memory for the presented words (i.e., true memory) in female, but not
      male, participants. These findings reveal that stress does not unequivocally
      enhance false memory production and that the timing of the stressor is an
      important variable that could mediate such effects. Such results could have
      important implications for understanding the dependability of eyewitness accounts
      of events that are observed following stress.

PMID- 24560842
TI  - Active maternal phenotype is established before breeding and leads offspring to
      align growth trajectory outcomes and reflex ontogeny.
AB  - The main goals of this study were to classify dams according to the level of
      voluntary physical activity before breeding and during pregnancy/lactation and to
      evaluate the effects on growth trajectory and reflex ontogenesis of offspring.
      Voluntary physical activity was ranked by traveled distance, time and daily
      estimated calorie burned. Thirty-five female Wistar rats were classified as
      control (C, n=5), inactive (I, n=10), active (A, n=8) and very active (VA, n=12).
      During 30d before breeding, traveled distance, average speed, time and calorie
      burned were daily recorded for active and very active groups. Traveled distance
      was recorded each 2h every day of adaptation. Body weight, food intake and
      fasting glycemia were measured throughout the experiment. During lactation,
      litters were evaluated in terms of physical features and reflex ontogeny. VA
      showed a progressive increase in the traveled distance and time while A dams
      presented constant values. VA rats showed lower body weight and higher food
      intake. During pregnancy, both groups performed less than 1km/day. Pups from A
      and VA dams showed higher lateral-lateral axis of the skull, longitudinal axis,
      tail length, and anticipation of the pavilion and auditory canal opening, and
      erupting incisors. I, A and VA groups showed a delay of righting, cliff aversion
      and vibrissae placing reflexes. In conclusion, active maternal phenotype is
      established before breeding allowing mothers to fit ecological and influencing
      growth trajectory outcomes and reflex ontogeny of the offspring based on
      matrilineal experience. 

PMID- 24560843
TI  - A transmembrane domain determines the localization of rice stripe virus pc4 to
      plasmodesmata and is essential for its function as a movement protein.
AB  - The pc4 protein encoded by rice stripe virus (RSV) is a viral movement protein
      (MP). A transmembrane (TM) domain spanning AAs 106-123 of pc4 was identified and
      shown to be essential for localization of pc4 to plasmodesmata (PD) (but not to
      chloroplasts) and for its ability to recover the movement of movement-deficient
      PVX. Analysis of alanine-scanning mutants showed that M116A and G120A had a
      similar localization to wild type pc4, being localized at PD and chloroplasts,
      but all other mutants were only localized at chloroplasts and not at PD. Mutants
      that could not be localized at PD had little (G123A) or no ability to recover PVX
      GFPDeltap25 movement, indicating that PD localization is crucial for the function
      of pc4 as a movement protein. Strangely, mutants M116A and G120A localized at PD
      and retained the ability to bind single-stranded RNA but did not support PVX
      GFPDeltap25 movement, indicating that properties other than PD localization and
      nucleotide binding ability may be needed for the function of pc4 as a movement
      protein. 

PMID- 24560844
TI  - EEG evolution in Sturge-Weber syndrome.
AB  - The EEG in Sturge-Weber syndrome (SWS) was theorized over 50 years ago as
      changing over time from normality to focal asymmetry to lastly epileptiform. We
      sought to validate these findings in a larger cohort today. Children with
      confirmed SWS and routine EEG at our center were evaluated retrospectively. An
      EEG score (0-3) was created and linked to patient current age, overall neurologic
      function, and seizure frequency. Eighty-one EEGs from 44 patients with SWS (mean
      age 2.0 years (range: 0.2-37.9 years)) were evaluated and assigned an EEG score.
      The mean age for patients with an EEG score of 0-1 (normal or focal slowing) was
      3.2 years (SEM 0.6), whereas those with an EEG score of 2-3 (focal sharp waves or
      frequent spike-wave bursts) was 8.7 years (SEM 1.7) (p=0.006). There was no
      correlation between the EEG score and either the SWS overall neuroscore or
      seizure subscore (measuring frequency). The EEG in patients with SWS does appear
      to evolve over time, becoming more abnormal with more frequent epileptiform
      activity, as suspected in smaller studies decades ago. This progressive change,
      however, did not correlate with the child's neurologic function or seizure
      frequency. 

PMID- 24560845
TI  - Evaluation of JNJ-26489112 in patients with photosensitive epilepsy: a placebo
      controlled, exploratory study.
AB  - PURPOSE: To evaluate the activity of JNJ-26489112 in patients with photosensitive
      epilepsy and determine the doses that result in reduction or complete suppression
      of the intermittent photic stimulation (IPS) induced photoparoxysmal-EEG response
      (PPR). METHODS: In this multicenter, single-blind, within subject, placebo
      controlled, sequential dose, exploratory study, 12 adult patients (3 men; 9
      women) with idiopathic photosensitive epilepsy, with and without concomitant
      antiepileptic drug (AED) therapy, underwent standardized IPS under three eye
      conditions (open, during closure, and closed) for up to 12h after receiving a
      single oral dose of placebo on day 1, JNJ-26489112 on day 2, and a second dose of
      placebo on day 3. Based on review of the blinded EEG data, the standardized
      photosensitive range (SPR) (i.e., upper and lower frequencies of the IPS-induced
      PPR), was calculated for each eye condition at each time point. A positive
      response was defined as a reduction of the SPR in >=3 out of 4 consecutive time
      points in >=1 eye condition on either day 2 or 3 compared with baseline (day 1)
      while complete suppression was defined as disappearance of an IPS-induced PPR
      (i.e., SPR=0). For the first four patients (Cohort 1), JNJ-26489112 dose was 1000
      mg, and the dose was escalated to a maximum of 3000 mg in subsequent cohorts.
      Blood and plasma samples were collected for pharmacokinetic evaluations along
      with measurements of concurrent AED concentrations. Safety was also assessed.
      RESULTS: The majority of patients showed a positive response on day 2 following
      JNJ-26489112 administration: 3/4 patients (1000 mg dose), 3/4 patients (2000 mg
      dose), and 2/3 patients (3000 mg). There was an apparent dose-dependent effect
      observed in patients who exhibited complete suppression of the SPR: 0/4 patients
      (1000 mg dose), 1/4 patient (2000 mg dose), and 2/3 patients (3000 mg dose). The
      median tmax of JNJ-26489112 (range: 3.73-5.04 h) in plasma was similar across all
      3 dose groups and plasma exposure of JNJ-26489112 increased proportionally with
      dose; approximate mean Cmax of 16, 28, and 42 MUg/mL for the 1000-, 2000-, and
      3000 mg cohorts, respectively. Concentrations of other AEDs did not appear to be
      affected by co-administration of JNJ-26489112. JNJ-26489112 was generally well
      tolerated with the most frequent adverse events (>10%) reported being mild
      headache, dizziness, and nausea. CONCLUSION: Single oral doses of JNJ-26489112
      were well-tolerated and the pharmacodynamic effects appeared to be dose-related
      in patients with idiopathic, photosensitive epilepsy.

PMID- 24560846
TI  - Delivery of operative pediatric surgical care by physicians and non-physician
      clinicians in Malawi.
AB  - BACKGROUND: Specialized pediatric surgeons are unavailable in much of sub-Saharan
      Africa. Delegating some surgical tasks to non-physician clinical officers can
      mitigate the dependence of a health system on highly skilled clinicians for
      specific services. METHODS: We performed a case-control study examining pediatric
      surgical cases over a 12 month period. Operating surgeon was categorized as
      physician or clinical officer. Operative acuity, surgical subspecialty, and
      outcome were then compared between the two groups, using physicians as the
      control. RESULTS: A total of 1186 operations were performed on 1004 pediatric
      patients. Mean age was 6 years (+/-5) and 64% of patients were male. Clinical
      officers performed 40% of the cases. Most general surgery, urology and congenital
      cases were performed by physicians, while most ENT, neurosurgery, and burn
      surgery cases were performed by clinical officers. Reoperation rate was higher
      for patients treated by clinical officers (17%) compared to physicians (7.1%),
      although this was attributable to multiple burn surgical procedures. Physician
      and clinical officer cohorts had similar complication rates (4.5% and 4.0%,
      respectively) and mortality rates (2.5% and 2.1%, respectively). DISCUSSION:
      Fundamental changes in health policy in Africa are imperative as a significant
      increase in the number of surgeons available in the near future is unlikely. Task
      shifting from surgeons to clinical officers may be useful to provide coverage of
      basic surgical care.

PMID- 24560847
TI  - Liver resection using cavitron ultrasonic surgical aspirator (CUSA) versus
      harmonic scalpel: a retrospective cohort study.
AB  - BACKGROUND: The aim of this study was to evaluate the safety and efficacy of two
      device combinations used in parenchymal division during hepatic resections in non
      cirrhotic patients and without inflow vascular occlusion. METHODS: We
      retrospectively analyzed 47 patients who underwent liver resection at our
      Institution from 2004 to 2010 using the TissueLink with either the Cavitron
      Ultrasonic Surgical Aspirator (CUSA) or the Harmonic Scalpel. The TissueLink was
      used with the CUSA in 27 patients and with the Harmonic Scalpel in 20 patients.
      RESULTS: Median estimated blood loss (EBL) in the Harmonic Scalpel and CUSA
      groups was 250 and 1035 mL respectively (p < 0.05). Three patients were
      transfused banked blood perioperatively in the Harmonic Scalpel group and 11 in
      the CUSA group (p < 0.05). Median operative time in the Harmonic Scalpel and CUSA
      groups was 185 and 290 min respectively. Length of stay (LOS) was shorter in the
      Harmonic Scalpel group at 6 days compared to 7 days in the CUSA group (p < 0.05).
      Perioperative complications were documented in 20% and 26% in the Harmonic
      Scalpel and CUSA groups, respectively. CONCLUSIONS: Our results show the Harmonic
      Scalpel with TissueLink to be a safe, effective method of parenchymal division
      with significantly less EBL and LOS when compared to CUSA with TissueLink.

PMID- 24560848
TI  - Long term predictors of success after laparoscopic sleeve gastrectomy.
AB  - BACKGROUND: To evaluate early, mid and long term efficacy of laparoscopic sleeve
      gastrectomy as a definitive management of morbid obesity and to study factors
      that may predict its success. MATERIALS AND METHODS: A retrospective study was
      conducted by reviewing the database of patients who underwent LSG as a definitive
      bariatric procedure, from April 2005 to March 2013. Univariate and multivariate
      analysis were performed. RESULTS: 1395 patients were included in this study. Mean
      age was 33 years and women:men ratio was 74:26. The mean preoperative BMI was 46
      kg/m(2). Operative time was 113 +/- 29 min. Reinforcement of staple line was done
      only in 447 (32%) cases. 11 (0.79%) cases developed postoperative leak, with
      total number of complications 72 (5.1%) and 0% mortality. Percentage of excess
      weight loss (%EWL) was 42%, 53%, 61%, 73%, 67%, 61%, 59% and 57% at 6 months, 1-7
      years. Remission of diabetes (DM), hypertension (HTN) and hyperlipidaemia (HLP)
      occurred 69%, 54% and 43% respectively. 56 (4%) patients underwent revision
      surgery, for insufficient weight loss (n = 37) and severe reflux symptoms (n =
      19). Mean follow up was 76 +/- 19 (range: 6-103) months. Smaller bougie size and
      leaving smaller antrum were associated with significant %EWL. Bougie <=36F
      remained significant in multivariate analysis. CONCLUSION: This study supports
      safety, effectiveness and durability of LSG as a sole definitive bariatric
      procedure. Smaller bougie size and shorter distance from pylorus were associated
      with significant %EWL.

PMID- 24560849
TI  - Diagnosing abdominal tuberculosis in the acute abdomen.
AB  - BACKGROUND: Despite recent improvements in medical treatments, the incidence of
      abdominal tuberculosis (ATB) in the United Kingdom has increased over the past
      two decades. This case series examined the difficulties encountered in correctly
      diagnosing this infection. PATIENTS AND METHODS: A retrospective study was
      undertaken, reviewing the records of 36 patients diagnosed with ATB from 2000 to
      2012 at a district general hospital in outer East London. RESULTS: The commonest
      presenting feature was abdominal pain in 67% of patients, and the most common
      sites of infection were the iliocaecal junction and peritoneum, seen in 36.1% and
      33.3% respectively. Six patients were initially investigated for Crohn's disease
      and one for ileitis. The highest disease prevalence was seen in patients born in
      India and Pakistan, which was 27.8% and 19.4% of patients respectively.
      Colonoscopy was performed in nine patients, and three of these reported normal
      findings. The other six reported visible non-specific inflammatory changes. Three
      patients had abdominal X-rays reported and one patient had an abdominal
      ultrasound, all of which were normal. An abdominal computerised topography (CT)
      scan was performed in 26 patients and a chest CT was undertaken in 19 patients.
      Varying degrees of inflammatory changes were seen in all of the patients who had
      CT scans. Microbiological culture was positive for Mycobacterium tuberculosis or
      acid-fast bacilli in 71% of patients. CONCLUSIONS: Abdominal tuberculosis can be
      very difficult to diagnose as symptoms are non-specific and can mimic other types
      of granulomatous inflammatory bowel diseases. Radiology appears largely unhelpful
      due to the non-specificity of any positive imaging findings, and there is a lack
      of diagnostic procedural and microbiological tests with high specificity and
      sensitivity. In view of the increasing incidence of tuberculosis in London, there
      should be a high index of suspicion for ATB in individuals from high-incidence
      countries who present with non-specific abdominal symptoms.

PMID- 24560850
TI  - Evaluation of thermal neutron irradiation field using a cyclotron-based neutron
      source for alpha autoradiography.
AB  - It is important to measure the microdistribution of (10)B in a cell to predict
      the cell-killing effect of new boron compounds in the field of boron neutron
      capture therapy. Alpha autoradiography has generally been used to detect the
      microdistribution of (10)B in a cell. Although it has been performed using a
      reactor-based neutron source, the realization of an accelerator-based thermal
      neutron irradiation field is anticipated because of its easy installation at any
      location and stable operation. Therefore, we propose a method using a cyclotron
      based epithermal neutron source in combination with a water phantom to produce a
      thermal neutron irradiation field for alpha autoradiography. This system can
      supply a uniform thermal neutron field with an intensity of 1.7*10(9) (cm(-2)s(
      1)) and an area of 40mm in diameter. In this paper, we give an overview of our
      proposed system and describe a demonstration test using a mouse liver sample
      injected with 500mg/kg of boronophenyl-alanine. 

PMID- 24560851
TI  - Quality control assurance of strontium-90 in foodstuffs by LSC.
AB  - A method based on the separation of Sr-90 by extraction chromatography and beta
      determination by Liquid Scintillation Counting (LSC) technique was used for
      strontium analysis in food samples. The methodology consisted in prior sample
      treatment (drying and incineration) followed by radiochemical separation of Sr-90
      by extraction chromatography, using the Sr-resin. The chemical yield was
      determined by gravimetric method, adding stable strontium to the matrix. Beta
      activity (Sr-90/Y-90) was determined using a low background liquid scintillation
      spectrometer (Tri-Carb 3170 TR/SL, Packard). The accuracy and the precision of
      the method, was performed previously through recovery trials with Sr-90 spiked
      samples, using the same type of matrices (milk, complete meals, meat and
      vegetables). A reference material (IAEA_321) was now used to measure the accuracy
      of the procedure. Participation in interlaboratory comparison exercises was also
      performed in order to establish an external control on the measurements and to
      ensure the adequacy of the method. 

PMID- 24560852
TI  - Characteristic parameters in the measurement of (14)C of biobased diesel fuels by
      liquid scintillation.
AB  - The direct method based on the radiocarbon content present in modern-day
      materials used for the quantification of the renewable origin component in diesel
      has been analysed in order to establish the best sample preparation and measuring
      conditions that minimise the limit of detection. The scintillation cocktail and
      the diesel/cocktail ratio have been optimised. 

PMID- 24560853
TI  - An unusual cause of painless jaundice. Renal cell carcinoma (Stauffer syndrome).

PMID- 24560854
TI  - A rare cause of gastrointestinal bleeding in the intensive care unit. Healthcare
      associated mucormycosis.

PMID- 24560855
TI  - An infant with vomiting, diarrhea, and failure to thrive. Chylomicron retention
      disease.

PMID- 24560856
TI  - Abnormal liver function tests in the third trimester: a diagnostic dilemma. Acute
      fatty liver of pregnancy.

PMID- 24560857
TI  - A CCL chemokine-derived peptide (CDIP-2) exerts anti-inflammatory activity via
      CCR1, CCR2 and CCR3 chemokine receptors: Implications as a potential therapeutic
      treatment of asthma.
AB  - Allergic asthma is a chronic inflammatory disease characterized by the
      accumulation of eosinophils, Th2 cells and mononuclear cells in the airways,
      leading to changes in lung architecture and subsequently reduced respiratory
      function. We have previously demonstrated that CDIP-2, a chemokine derived
      peptide, reduced in vitro chemotaxis and decreased cellular infiltration in a
      murine model of allergic airway inflammation. However, the mechanisms involved in
      this process have not been identified yet. Now, we found that CDIP-2 reduces
      chemokine-mediated functions via interactions with CCR1, CCR2 and CCR3. Moreover,
      using bone marrow-derived eosinophils, we demonstrated that CDIP-2 modifies the
      calcium fluxes induced by CCL11 and down-modulated CCR3 expression. Finally, CDIP
      2 treatment in a murine model of OVA-induced allergic airway inflammation reduced
      leukocyte recruitment and decreases production of cytokines. These data suggest
      that chemokine-derived peptides represent new therapeutic tools to generate more
      effective antiinflammatory drugs. 

PMID- 24560858
TI  - Polygala molluginifolia A. St.-Hil. and Moq. prevent inflammation in the mouse
      pleurisy model by inhibiting NF-kappaB activation.
AB  - This study was conducted to investigate the anti-inflammatory activity of
      Polygala molluginifolia (Polygalaceae) on the mouse pleurisy model induced by
      carrageenan. P. molluginifolia is a plant native to southern Brazil that is
      popularly called "canfora". The Polygala genus is used to treat different
      pathologies, including inflammatory diseases, in traditional medicine. MATERIAL
      AND METHODS: The whole P. molluginifolia plant material was extracted by
      maceration with 96% ethanol. The crude hydroalcoholic extract (CE) was subjected
      to chromatographic procedures to produce various derivate fractions, including
      its aqueous (Aq), ethyl acetate (EtOAc), and hexane (Hex) fractions. Compound 1
      (5,3',4'-trihydroxy-6",6"-dimethylpyrano [2",3":7,6] isoflavone) (Iso), which was
      isolated from the EtOAc fraction, and Compound 2 (rutin) (Rut), which was
      isolated from the Aq fraction, were identified using 1H and 13C NMR spectroscopy
      and quantified using an HPLC apparatus. RESULTS: The CE, the Aq, EtOAc, and Hex
      fractions, and the isolated compounds Iso and Rut were able to reduce cell
      migration and exudation. Furthermore, the plant material also decreased the
      myeloperoxidase (MPO) and adenosine-deaminase (ADA) activities and the nitric
      oxide (NO(x)), tumor necrosis factor-alpha (TNF-alpha), and interleukin-1 beta
      (IL-1beta) levels. In addition, Iso and Rut reduced the TNF-alpha and IL-1beta
      mRNA expression levels and significantly decreased NF-kappaB p65 phosphorylation.
      CONCLUSION: The results show that P. molluginifolia has a significant anti
      inflammatory action and that this effect is due, at least in part, to the
      presence of Iso and Rut in large amounts. Moreover, this effect was found to be
      closely related to the inhibitory effects of the isolated compounds on the NF
      kappaB pathway.

PMID- 24560859
TI  - Elucidating the neurotoxic effects of MDMA and its analogs.
AB  - AIMS: There is a rapid increase in the use of methylenedioxymethamphetamine
      (MDMA) and its structural congeners/analogs globally. MDMA and MDMA-analogs have
      been synthesized illegally in furtive dwellings and are abused due to its
      addictive potential. Furthermore, MDMA and MDMA-analogs have shown to have
      induced several adverse effects. Hence, understanding the mechanisms mediating
      this neurotoxic insult of MDMA-analogs is of immense importance for the public
      health in the world. MAIN METHODS: We synthesized and investigated the neurotoxic
      effects of MDMA and its analogs [4-methylenedioxyamphetamine (MDA), 2, 6
      methylenedioxyamphetamine (MDMA), and N-ethyl-3, 4-methylenedioxyamphetamine
      (MDEA)]. The stimulatory or the dopaminergic agonist effects of MDMA and MDMA
      analogs were elucidated using the established 6-hydroxydopamine lesioned animal
      model. Additionally, we also investigated the neurotoxic mechanisms of MDMA and
      MDMA-analogs on mitochondrial complex-I activity and reactive oxygen species
      generation. KEY FINDINGS: MDMA and MDMA-analogs exhibited stimulatory activity as
      compared to amphetamines and also induced several behavioral changes in the
      rodents. MDMA and MDMA-analogs enhanced the reactive oxygen generation and
      inhibited mitochondrial complex-I activity which can lead to neurodegeneration.
      Hence the mechanism of neurotoxicity, MDMA and MDMA-analogs can enhance the
      release of monoamines, alter the monoaminergic neurotransmission, and augment
      oxidative stress and mitochondrial abnormalities leading to neurotoxicity.
      SIGNIFICANCE: Thus, our study will help in developing effective pharmacological
      and therapeutic approaches for the treatment of MDMA and MDMA-analog abuse.

PMID- 24560860
TI  - Origin of the phagocytic respiratory burst and its role in gut epithelial
      phagocytosis in a basal chordate.
AB  - The vertebrate phagocytic respiratory burst (PRB) is a highly specific and
      efficient mechanism for reactive oxygen species (ROS) production. This mechanism
      is mediated by NADPH oxidase 2 (NOX2) and used by vertebrate phagocytic
      leukocytes to destroy internalized microbes. Here we demonstrate the presence of
      the PRB in a basal chordate, the amphioxus Branchiostoma belcheri tsingtauense
      (bbt). We show that using the antioxidant NAC to scavenge the production of ROS
      significantly decreased the survival rates of infected amphioxus, indicating that
      ROS are indispensable for efficient antibacterial responses. Amphioxus NOX
      enzymes and cytosolic factors were found to colocalize in the epithelial cells of
      the gill, intestine, and hepatic cecum and could be upregulated after exposure to
      microbial pathogens. The ROS production in epithelial cell lysates could be
      reconstructed by supplementing recombinant cytosolic factors, including bbt
      p47phox, bbt-p67phox, bbt-p47phox, and bbt-Rac; the restored ROS production could
      be inhibited by anti-bbt-NOX2 and anti-bbt-p67phox antibodies. We also reveal
      that the gut epithelial lining cells of the amphioxus are competent at bacterial
      phagocytosis, and there is evidence that the PRB machinery could participate in
      the initiation of this phagocytic process. In conclusion, we report the presence
      of the classical PRB machinery in nonvertebrates and provide the first evidence
      for the possible role of PRB in epithelial cell immunity and phagocytosis. 

PMID- 24560862
TI  - Ultrasound-guided percutaneous thrombin injection of iatrogenic upper extremity
      pseudoaneurysms.
AB  - OBJECTIVE: The objective of this study was to evaluate the safety and efficacy of
      ultrasound-guided thrombin injection (TI) for the treatment of upper extremity
      iatrogenic pseudoaneurysms (PAs) after percutaneous upper extremity arterial
      access. METHODS: This is a retrospective single-institution study from January
      2009 to December 2012. All patients with clinical suspicion of an upper extremity
      PA after arterial puncture underwent duplex examination. Patients with and
      without PAs were compared to identify risk factors for development of PAs.
      Outcomes were analyzed in those patients with PAs that were treated with TI.
      RESULTS: Between January 1, 2009, and December 31, 2012, there were 61 upper
      extremity arterial duplex examinations performed for a clinical suspicion of an
      upper extremity PA. Eighteen ultrasound examinations (29.5%) demonstrated an
      iatrogenic upper extremity PA (13 brachial and five radial). Those patients with
      an upper extremity PA were more likely to have a history of hypertension, atrial
      fibrillation, and chronic kidney disease. Sheath size, preprocedural antiplatelet
      therapy, periprocedural anticoagulation regimen, service specialty performing the
      procedure, and procedure type did not influence the development of PA. Of 18
      patients with PA, 14 were treated with TI with an overall success rate of 86%.
      There was one PA that failed to thrombose with TI, and there was one native
      brachial artery thrombosis requiring emergent surgical intervention. Outpatient
      clinical follow-up in the successfully treated patients demonstrated no
      recurrences at an average follow-up of 8 months. CONCLUSIONS: Ultrasound-guided
      percutaneous TI appears safe and effective for the treatment of iatrogenic
      brachial and radial artery PAs.

PMID- 24560863
TI  - Comparison of fenestrated endovascular aneurysm repair and chimney graft
      techniques for pararenal aortic aneurysm.
AB  - OBJECTIVE: This study compared early-term and midterm results of endovascular
      repair (EVAR) of juxtarenal or pararenal aortic aneurysms (PAAs) using
      fenestrated stent grafting (f-EVAR) and the chimney grafting (c-EVAR) technique.
      METHODS: Consecutive patients with PAAs who underwent f-EVAR using commercially
      available devices and c-EVAR in a tertiary vascular center from January 2006 to
      April 2013 were evaluated, including a retrospective scrutiny and update of a
      prospectively maintained database, calculation and comparison of perioperative
      mortality and morbidity, overall survival, reintervention-free rate, branch event
      free rate, reconstructed vessel patency, and collection of data about
      intraoperative events, perioperative complications and reinterventions, and
      midterm sac behavior. RESULTS: During the study period, 80 patients (72 men)
      underwent f-EVAR and 38 (34 men) underwent c-EVAR. All f-EVAR patients were
      operated on electively, whereas six c-EVAR patients (15.8%; P = .002) were
      operated on in an emergent setting. The preoperative PAA diameter was
      significantly smaller in the f-EVAR group than in the c-EVAR group (58.6 +/- 8.6
      mm vs 65.9 +/- 15.3 mm; P = .003). The mean number of reconstructed vessels per
      patient was 2.4 +/- 0.7 (median, two) for the f-EVAR group and 1.6 +/- 0.7
      (median, one) for the c-EVAR group (P < .0001). The f-EVAR and c-EVAR groups did
      not differ in 30-day mortality (6.3% vs 7.9%; P = .71) or in moderate to severe
      complications (27.5% vs 39.5%; P = 1.0). Median follow-up duration was 14 months,
      (range, 0-88 months) in the f-EVAR group and 12 months (range, 0-48 months) in
      the c-EVAR group. After 2 years, estimated survival rates (77.3% vs 71.8%),
      reintervention-free rates (71.4% vs 72.0%), reconstructed vessel event-free rates
      (90.5% vs 84.1%), and primary patency of reconstructed vessel rates (97.1% vs
      87.6%) were not statistically different. During follow-up, sac shrinkage (>=5 mm)
      was observed in 43.4% of f-EVAR patients and in 30.6% of c-EVAR patients (no
      statistical difference). CONCLUSIONS: In this limited retrospective series, short
      term and midterm results of f-EVAR and c-EVAR were not statistically different. c
      EVAR could be an attractive option for patients not suitable for f-EVAR.

PMID- 24560861
TI  - Differences in food environment perceptions and spatial attributes of food
      shopping between residents of low and high food access areas.
AB  - OBJECTIVE: To explore potential differences in food shopping behaviors and
      healthy food availability perceptions between residents living in areas with low
      and high food access. DESIGN: A cross-sectional telephone survey to assess food
      shopping behaviors and perceptions. Data from an 8-county food environment field
      census used to define the Centers for Disease Control and Prevention (CDC)
      healthier food retail tract and US Department of Agriculture Economic Research
      Service food desert measure. PARTICIPANTS: A total of 968 residents in 8 South
      Carolina counties. MAIN OUTCOME MEASURES: Residents' food shopping behaviors and
      healthy food availability perceptions. ANALYSIS: Linear and logistic regression.
      RESULTS: Compared with residents in high food access areas, residents in low food
      access areas traveled farther to their primary food store (US Department of
      Agriculture Economic Research Service: 8.8 vs 7.1 miles, P = .03; CDC: 9.2 vs 6.1
      miles, P < .001), accumulated more total shopping miles per week (CDC: 28.0 vs
      15.4 miles; P < .001), and showed differences in perceived healthy food
      availability (P < .001) and shopping access (P < .001). CONCLUSIONS AND
      IMPLICATIONS: These findings lend support to ongoing community and policy
      interventions aimed at reducing food access disparities.

PMID- 24560864
TI  - Impact of cumulative intravascular contrast exposure on renal function in
      patients with occlusive and aneurysmal vascular disease.
AB  - OBJECTIVE: Patients with occlusive or aneurysmal vascular disease are repeatedly
      exposed to intravascular (IV) contrast for diagnostic or therapeutic purposes. We
      sought to determine the long-term impact of cumulative iodinated IV contrast
      exposure (CIVCE) on renal function; the latter was defined by means of National
      Kidney Foundation (NKF) criteria. METHODS: We performed a longitudinal study of
      consecutive patients without renal insufficiency at baseline (NFK stage I or II)
      who underwent interventions for arterial occlusive or aneurysmal disease. We
      collected detailed data on any IV iodinated contrast exposure (including
      diagnostic or therapeutic angiography, cardiac catheterization, IV pyelography,
      computed tomography with IV contrast, computed tomographic angiography);
      medication exposure throughout the observation period; comorbidities; and
      demographics. The primary end point was the development of renal failure (RF)
      (defined as NFK stage 4 or 5). Analysis was performed with the use of a shared
      frailty model with clustering at the patient level. RESULTS: Patients (n = 1274)
      had a mean follow-up of 5.8 (range, 2.2-14) years. In the multivariate model with
      RF as the dependent variable and after adjusting for the statistically
      significant covariates of baseline renal function (hazard ratio [HR], 0.95; P <
      .001), diabetes (HR, 1.8; P = .007), use of an angiotensin-converting enzyme
      inhibitor (HR, 0.63; P = .03), use of antiplatelets (HR, 0.5; P = .01),
      cumulative number of open vascular operations performed (HR, 1.2; P = .001), and
      congestive heart failure (HR, 3.2; P < .001), CIVCE remained an independent
      predictor for RF development (HR, 1.1; P < .001). In the multivariate survival
      analysis model and after adjusting for the statistically significant covariates
      of perioperative myocardial infarction (HR, 3.9; P < .001), age at entry in the
      cohort (HR, 1.05; P = .035), total number of open operations (HR, 1.51; P <
      .001), and serum albumin (HR, 0.47; P < .001), CIVCE was an independent predictor
      of death (HR, 1.07; P < .001). CONCLUSIONS: Cumulative IV contrast exposure is an
      independent predictor of RF and death in patients with occlusive and aneurysmal
      vascular disease.

PMID- 24560865
TI  - Epidemiology of aortic aneurysm repair in the United States from 2000 to 2010.
AB  - OBJECTIVE: Broad application of endovascular aneurysm repair (EVAR) has led to a
      rapid decline in open aneurysm repair (OAR) and improved patient survival, albeit
      at a higher overall cost of care. The aim of this report is to evaluate national
      trends in the incidence of unruptured and ruptured abdominal aortic aneurysms
      (AAAs), their management by EVAR and OAR, and to compare overall patient
      characteristics and clinical outcomes between these two approaches. METHODS: A
      retrospective analysis of the cross-sectional National Inpatient Sample (2000
      2010) was used to evaluate patient characteristics and outcomes related to EVAR
      and OAR for unruptured and ruptured AAAs. Data were extrapolated to represent
      population-level statistics through the use of data from the U.S. Census Bureau.
      Comparisons between groups were made with the use of descriptive statistics.
      RESULTS: There were 101,978 patients in the National Inpatient Sample affected by
      AAAs over the 11-year span of this study; the average age was 73 years, 21% were
      women, and 90% were white. Overall in-hospital mortality rate was 7%, with a
      median length of stay (LOS) of 5 days and median hospital charges of $58,305. In
      hospital mortality rate was 13 times greater for ruptured patients, with a median
      LOS of 9 days and median charges of $84,744. For both unruptured and ruptured
      patients, EVAR was associated with a lower in-hospital mortality rate (4% vs 1%
      for unruptured and 41% vs 27% for ruptured; P < .001 for each), shorter median
      LOS (7 vs 2; 9 vs 6; P < .001) but a 27%-36% increase in hospital charges.
      CONCLUSIONS: The overall use of EVAR has risen sharply in the past 10 years (5.2%
      to 74% of the total number of AAA repairs) even though the total number of AAAs
      remains stable at 45,000 cases per year. In-hospital mortality rates for both
      ruptured and unruptured cases have fallen by more than 50% during this time
      period. Lower mortality rates and shorter LOS despite a 27%-36% higher cost of
      care continues to justify the use of EVAR over OAR. For patients with suitable
      anatomy, EVAR should be the preferred management of both ruptured and unruptured
      AAAs.

PMID- 24560866
TI  - Endovascular treatment of symptomatic high-grade vertebral artery stenosis.
AB  - BACKGROUND: The purpose of this study was to evaluate the initial and long-term
      results of endovascular treatment (EVT) in patients with symptomatic high-grade
      extracranial vertebral artery (VA) origin stenosis. METHODS: From February 2001
      to March 2013, 73 consecutive patients (33 men with a mean age of 61.7 +/- 8.8
      years) underwent EVT for symptomatic high-grade VA stenosis. Preoperative
      evaluation included Duplex ultrasonography and arteriography. After successful
      treatment, all patients were followed up at 1, 3, 6, and 12 months after the
      procedure and every 6 months thereafter. RESULTS: Successful EVT of the VA
      stenosis was achieved in 68 patients (93.2%). All procedures were performed
      without use of cerebral protection. The early complication rate was 5.5%, which
      included one periprocedural transient ischemic attack, two hematomas at the
      puncture site, and one allergic reaction to the contrast agent. No in-hospital
      deaths occurred. During follow-up (mean, 44.3 +/- 31.2 months; range, 2-144
      months), the primary patency rates at 1, 3, 5, and 7 years were 98.4%, 87.3%,
      87.3%, and 87.3%, respectively. Ultrasound Doppler controls during follow-up
      detected seven VA restenoses (10.3%). Univariate analysis failed to identify any
      variable predictive of long-term patency of successfully treated VA stenosis.
      CONCLUSIONS: EVT of symptomatic VA origin stenosis is a safe and effective
      procedure associated with low risk and good long-term results, even without use
      of cerebral protection devices.

PMID- 24560867
TI  - Impact of postoperative transient ischemic attack on survival after carotid
      revascularization.
AB  - OBJECTIVE: Major postoperative complications such as stroke and myocardial
      infarction are usually carefully evaluated in the analysis of carotid
      revascularization performance. Although transient ischemic attacks (TIAs) are
      often left unreported, they also may influence long-term outcome. The aim of our
      study was to evaluate the influence of postoperative TIA in the long-term
      survival of patients submitted to carotid revascularization. METHODS: All
      consecutive patients submitted to either carotid artery stenting or carotid
      endarterectomy for symptomatic or asymptomatic carotid stenosis from 2005 to 2012
      were retrospectively analyzed. Patients were stratified according to their
      postoperative (30-day) neurologic course (no symptoms, TIA, or stroke). Kaplan
      Maier with log-rank analysis was performed to compare the 5-year survival of
      patients with postoperative TIA, stroke, or neither; factors affecting the 5-year
      mortality were evaluated by multivariable Cox proportional hazards models.
      RESULTS: Over a total of 1390 carotid revascularizations (carotid endarterectomy,
      n = 868 [62.4%]; carotid artery stenting, n = 522 [37.6%]), neurological
      perioperative complications occurred in 67 (4.7%) cases (38, 2.7% TIA; 29, 2.0%
      stroke). At 5-year follow-up, overall survival was significantly lower in
      patients with postoperative TIA (78.4 +/- 8.0% vs 97.4 +/- 0.6%; P < .001) and
      postoperative stroke (68.2 +/- 14.4% vs 97.4 +/- 0.6%; P = .03) compared with
      patients without neurological complications. By means of multivariate Cox
      analysis, postoperative TIA and stroke were independent predictors of decreased
      survival (hazard ratio [HR], 3.10; 95% confidence interval [CI], 1.01-9.72; P =
      .04, and HR, 3.87; 95% CI, 1.13-13.19; P = .03, respectively), other than age >80
      years, postoperative myocardial infarction, and chronic renal failure (HR, 2.07;
      95% CI, 1.41-4.90; P = .01; HR, 4.33; 95% CI, 2.74-23.79; P = .04; HR, 2.54; 95%
      CI, 1.04-6.19; P = .04, respectively). CONCLUSIONS: TIAs are significant events,
      possibly determined by a wider extent of atherosclerotic disease, with important
      effects on long-term mortality similar to that in strokes. Different from most
      trials evaluating the outcomes of revascularization techniques, the incidence of
      perioperative TIA should be accurately considered in the analysis.

PMID- 24560868
TI  - The tumor necrosis factor family member TNFSF14 (LIGHT) is required for
      resolution of intestinal inflammation in mice.
AB  - BACKGROUND & AIMS: The pathogenesis of inflammatory bowel disease (IBD) is
      associated with a dysregulated mucosal immune response. Expression of the tumor
      necrosis factor (TNF) superfamily member 14 (TNFSF14, also known as LIGHT
      [homologous to lymphotoxins, exhibits inducible expression, and competes with HSV
      glycoprotein D for HVEM, a receptor expressed by T lymphocytes]) on T cells is
      involved in their activation; transgenic expression of LIGHT on T cells in mice
      promotes inflammation in multiple organs, including intestine. We investigated
      the roles for LIGHT in recovery from intestinal inflammation in mice. METHODS: We
      studied the role of LIGHT in intestinal inflammation using Tnfsf14(-/-) and wild
      type mice. Colitis was induced by transfer of CD4(+)CD45RB(high) T cells into
      Rag1(-/-) or Tnfsf14(-/-)Rag1(-/-) mice, or by administration of dextran sulfate
      sodium to Tnfsf14(-/-) or wild-type C57BL/6J mice. Mice were weighed, colon
      tissues were collected and measured, and histology analyses were performed. We
      measured infiltrating cell populations and expression of cytokines, chemokines,
      and LIGHT. RESULTS: After administration of dextran sulfate sodium, Tnfsf14(-/-)
      mice developed more severe colitis than controls, based on their reduced
      survival, accelerated loss of body weight, and histologic scores. LIGHT protected
      mice from colitis via the lymphotoxin beta receptor and was expressed mainly by
      myeloid cells in the colon. Colons of Tnfsf14(-/-) mice also had increased
      accumulation of innate immune cells and higher levels of cytokines than colons
      from control mice. LIGHT, therefore, appears to regulate inflammation in the
      colon. CONCLUSIONS: Tnfsf14(-/-) mice develop more severe colitis than control
      mice. LIGHT signals through the lymphotoxin beta receptor in the colon to
      regulate the innate immune response and mediate recovery from intestinal
      inflammation.

PMID- 24560870
TI  - Role of the microbiome in energy regulation and metabolism.
AB  - Intestinal microbes regulate metabolic function and energy balance; an altered
      microbial ecology is believed to contribute to the development of several
      metabolic diseases. Relative species abundance and metabolic characteristics of
      the intestinal microbiota change substantially in those who are obese or have
      other metabolic disorders and in response to ingested nutrients or therapeutic
      agents. The mechanisms through which the intestinal microbiota and its
      metabolites affect host homeostasis are just beginning to be understood. We
      review the relationships between the intestinal microbiota and host metabolism,
      including energy intake, use, and expenditure, in relation to glucose and lipid
      metabolism. These associations, along with interactions among the intestinal
      microbiota, mucus layer, bile acids, and mucosal immune responses, reveal
      potential mechanisms by which the microbiota affect metabolism. We discuss how
      controlled studies involving direct perturbations of microbial communities in
      human and animal models are required to identify effective therapeutic targets in
      the microbiota.

PMID- 24560871
TI  - Association of head, thoracic and abdominal trauma with delayed diagnosis of co
      existing injuries in critical trauma patients.
AB  - BACKGROUND: Management of critically injured patients is usually complicated and
      challenging. A structured team approach with comprehensive survey is warranted.
      However, delayed diagnosis of co-existing injuries that are less severe or occult
      might still occur, despite a standard thorough approach coupled with advances in
      image intervention. Clinicians are easily distracted or occupied by the more
      obvious or threatening conditions. We hypothesised that the major area of injured
      body regions might contribute to this unwanted condition. METHODS: A
      retrospective study of all trauma patients admitted to our surgical intensive
      care units (ICU) was performed to survey the incidence of delayed diagnosis of
      injury (DDI) and the association between main body region injured and possibility
      of DDI. Demographic data and main body regions injured were compared and
      statistically analysed between patients with and without DDI. RESULTS: During the
      two-year study period, a total 976 trauma patients admitted to our surgical ICU
      were included in this study. The incidence of DDI was 12.1% (118/976). Patients
      with DDI had higher percentages of thoracic, abdominal, and pelvic injuries
      (30.5%, 16.1%, and 7.6% respectively) than the non-DDI group (14.7%, 7.5%, and
      3.0% respectively) (p<0.001, 0.003, and 0.024 respectively). A logistic
      regression model demonstrated that head (odds ratio=1.99; 95%CI=1.20-3.31),
      thoracic (odds ratio=2.44; 95%CI=1.55-3.86), and abdominal injuries (odds
      ratio=2.38; 95%CI=1.28-4.42) were independently associated with increasing DDI in
      patients admitted to the surgical ICU. DISCUSSION: In conclusion, critical trauma
      patients admitted to the surgical ICU with these categories of injuries were more
      likely to have DDI. Clinicians should pay more attention to patients admitted due
      to injuries in these regions. More detailed and dedicated secondary and tertiary
      surveys should be given, with more frequent and careful re-evaluation.

PMID- 24560869
TI  - The microbiome in inflammatory bowel disease: current status and the future
      ahead.
AB  - Studies of the roles of microbial communities in the development of inflammatory
      bowel disease (IBD) have reached an important milestone. A decade of genome-wide
      association studies and other genetic analyses have linked IBD with loci that
      implicate an aberrant immune response to the intestinal microbiota. More
      recently, profiling studies of the intestinal microbiome have associated the
      pathogenesis of IBD with characteristic shifts in the composition of the
      intestinal microbiota, reinforcing the view that IBD results from altered
      interactions between intestinal microbes and the mucosal immune system. Enhanced
      technologies can increase our understanding of the interactions between the host
      and its resident microbiota and their respective roles in IBD from both a large
      scale pathway view and at the metabolic level. We review important microbiome
      studies of patients with IBD and describe what we have learned about the
      mechanisms of intestinal microbiota dysfunction. We describe the recent progress
      in microbiome research from exploratory 16S-based studies, reporting associations
      of specific organisms with a disease, to more recent studies that have taken a
      more nuanced view, addressing the function of the microbiota by metagenomic and
      metabolomic methods. Finally, we propose study designs and methodologies for
      future investigations of the microbiome in patients with inflammatory gut and
      autoimmune diseases in general.

PMID- 24560872
TI  - Massive blood transfusions post trauma in the elderly compared to younger
      patients.
AB  - INTRODUCTION: Older age and blood transfusion have both been independently
      associated with higher mortality post trauma and the combination is expected to
      be associated with catastrophic outcomes. Among patients who received a massive
      transfusion post trauma, we aimed to investigate mortality at hospital discharge
      of patients >=65 years old and explore variables associated with poor outcomes.
      METHODS: A retrospective review of registry data on all major trauma patients
      presenting to a level I trauma centre between 2006 and 2011 was conducted.
      Mortality at hospital discharge among patients >=65 years old was compared to the
      younger cohort. A multivariable logistic regression model was constructed to
      determine independent risk-factors for mortality among older patients. RESULTS:
      There were 51 (16.4%) patients of age >=65 years who received a massive
      transfusion. There were 20 (39.2%) deaths, a proportion significantly higher than
      55 (21.1%) deaths among younger patients (p<0.01). Pre-hospital GCS, the presence
      of acute traumatic coagulopathy and higher systolic blood pressure on
      presentation were independently associated with higher mortality. Age and volume
      of red cells transfused were not significantly associated with higher mortality.
      CONCLUSIONS: Survival to hospital discharge was demonstrated in elderly patients
      receiving massive transfusions post trauma, even in the presence of multiple risk
      factors for mortality. Restrictive resuscitation or transfusion on the basis of
      age alone cannot be supported. Early aggressive resuscitation of elderly trauma
      patients along specific guidelines directed at the geriatric population is
      justified and may further improve outcomes.

PMID- 24560873
TI  - The impact of genital trauma on wounded servicemen: qualitative study.
AB  - BACKGROUND: Recent military operations in Afghanistan have resulted in
      considerable lower limb trauma. Associated with this trauma have been serious
      injuries to the genitalia. No previous study has looked at the effect of
      traumatic genital injury on the individual. This study expresses the impact of
      these injuries. METHODS: A qualitative evaluation, interviewing 13 male patients
      with extensive genital injuries, including 11 patients with orchidectomies.
      RESULTS: Patients attach a very high importance to their genital injury, rating
      this injury as having more impact than lower limb amputations. They also have a
      high expectation for the recovery of sexual function. Psychological outcomes are
      better when an individual's future fertility is known at an early stage.
      CONCLUSION: Better outcomes are achieved for the patient when psychological and
      surgical support if provided throughout the long treatment and recovery process
      It is important that every effort is made to preserve fertility right from the
      point of injury.

PMID- 24560874
TI  - The relation of aerobic fitness to cognitive control and heart rate variability:
      a neurovisceral integration study.
AB  - This aim of the present study was to investigate relationships between aerobic
      fitness, sympathetic and parasympathetic cardiac control using pre-ejection
      period (PEP) and high frequency heart rate variability (HF HRV), and performance
      on a task requiring variable amounts of cognitive control. Fifty-six participants
      completed a modified-version of the Eriksen flanker task while PEP and HF HRV
      were collected. A graded maximal exercise test was subsequently used to measure
      aerobic fitness by assessing maximal oxygen uptake. Results indicated a
      significant relation of fitness to reaction time performance. Although no fitness
      differences were observed in resting state PEP or HF HRV, higher fit adults
      exhibited greater task-induced parasympathetic cardiac control. However, no
      significant mediation was found for HF HRV on the fitness-cognitive control
      relationship, suggesting other mediators may be important. These findings
      highlight the role of aerobic fitness in enhancing integrated autonomic and
      neurocognitive health. 

PMID- 24560875
TI  - Antigenicity studies in humans and immunogenicity studies in mice: an MSP1P
      subdomain as a candidate for malaria vaccine development.
AB  - The newly identified GPI-anchored Plasmodium vivax merozoite surface protein 1
      paralog (MSP1P) has a highly antigenic C-terminus that binds erythrocytes. To
      characterize the antigenicity and immunogenicity of two regions (PvMSP1P-19 and 
      33) of the highly conserved C-terminus of MSP1P relative to PvMSP1-19, 30 P.
      vivax malaria-infected patients and two groups of mice (immunized with PvMSP1P-19
      or -33) were tested for IgG subclass antibodies against PvMSP1P-19 and -33
      antigens. In the patients infected with P. vivax, IgG1 and IgG3 levels were
      significantly higher than those levels in healthy individuals, and were the
      predominant response to the two C-terminal fragments of PvMSP1P (p < 0.05). In
      mice immunized with PvMSP1P-19, IgG1 levels were the highest while IgG2b levels
      were similar to IgG1 levels. The levels of Th1 cytokines in mice immunized with
      PvMSP1P-19 or -33 were significantly higher than those in mice immunized with
      PvMSP1-19 (p < 0.05). Our results indicate that: (i) IgG1 and IgG3 (IgG2b in
      mice) are predominant IgG subclasses in both patients infected with P. vivax and
      mice immunized with PvMSP1P-19 or -33; (ii) the C-terminus of MSP1P induces a Th1
      cytokine response. This immune profiling study provides evidence that MSP1P may
      be a potential candidate for vivax vaccine. 

PMID- 24560876
TI  - D-alpha-tocopheryl polyethylene glycol succinate (TPGS) induces cell cycle arrest
      and apoptosis selectively in Survivin-overexpressing breast cancer cells.
AB  - D-alpha-tocopheryl polyethylene glycol succinate (TPGS) is a vitamin E derivative
      that has been intensively applied as a vehicle for drug delivery systems to
      enhance drug solubility and increase the oral bioavailability of anti-cancer
      drugs. Recently, it has been reported that TPGS acts as an anti-cancer agent
      alone or synergistically with chemotherapeutic drugs and increases the efficacy
      of nanoparticle formulations. In this study, we investigated the antitumor
      efficacy and the molecular mechanism of action of TPGS in breast cancer cell
      lines. Our results show that TPGS can induce G1/S cell cycle arrest and apoptosis
      in breast cancer cell lines (MCF-7 and MDA-MB-231) but not in "normal" (non
      tumorigenic) immortalized cells (MCF-10A and MCF-12F). An investigation of the
      molecular mechanism of action of TPGS reveals that induction of G1/S phase cell
      cycle arrest is associated with upregulation of P21 and P27Kip1 proteins.
      Induction of apoptosis by TPGS involves the inhibition of phospho-AKT and the
      downregulation of the anti-apoptotic proteins Survivin and Bcl-2. Interestingly,
      our results also suggest that TPGS induces both caspase -dependent and 
      independent apoptotic signaling pathways and that this vitamin E derivative is
      selectively cytotoxic in breast cancer cell lines. When compared to the Survivin
      inhibitor YM155, TPGS was shown to be more selective for cancer cell growth
      inhibition. Overall our results suggest that TPGS may not only be useful as a
      carrier molecule for drug delivery, but may also exert intrinsic therapeutic
      effects suggesting that it may promote a synergistic interaction with formulated
      chemotherapeutic drugs.

PMID- 24560879
TI  - Type A botulinum neurotoxin complex proteins differentially modulate host
      response of neuronal cells.
AB  - Type A Botulinum neurotoxin (BoNT/A), the most potent poison known to mankind, is
      produced by Clostridium botulinum type A as a complex with neurotoxin-associated
      proteins (NAPs). Currently BoNT/A in purified and complex forms are both
      available in therapeutic and cosmetic applications to treat neuromuscular
      disorders. Whereas Xeomin((r)) (incobotulinumtoxin A, Merz Pharmaceuticals,
      Germany) is free from complexing proteins, Botox((r)) (onabotulinumtoxin A,
      Allergan, USA) contains NAPs, which by themselves have no known role in the
      intracellular biochemical process involved in the blockade of neurotransmitter
      release. Since the fate and possible interactions of NAPs with patient tissues
      after intramuscular injection are not known, it was the aim of this study to
      evaluate the binding of BoNT/A and/or the respective NAPs to cells derived from
      neuronal and non-neuronal human tissues, and to further explore neuronal cell
      responses to different components of BoNT/A. BoNT/A alone, the complete BoNT/A
      complex, and the NAPs alone, all bind to neuronal SH-SY5Y cells. The BoNT/A
      complex and NAPs additionally bind to RMS13 skeletal muscle cells, TIB-152
      lymphoblasts, Detroit 551 fibroblasts besides the SH-SY5Y cells. However, no
      binding to these non-neuronal cells was observed with pure BoNT/A. Although
      BoNT/A, both in its purified and complex forms, bind to SH-SY5Y, the
      intracellular responses of the SH-SY5Y cells to these BoNT/A components are not
      clearly understood. Examination of inflammatory cytokine released from SH-SY5Y
      cells revealed that BoNT/A did not increase the release of inflammatory
      cytokines, whereas exposure to NAPs significantly increased release of IL-6, and
      MCP-1, and exposure to BoNT/A complex significantly increased release of IL-6,
      MCP-1, IL-8, TNF-alpha, and RANTES vs. control, suggesting that different
      components of BoNT/A complex induce significantly differential host response in
      human neuronal cells. Results suggest that host response to different
      compositions of BoNT/A based therapeutics may play important role in local and
      systemic symptoms in patients. 

PMID- 24560878
TI  - Rheumatoid arthritis quality measures and radiographic progression.
AB  - OBJECTIVE: Documentation of quality measures (QMs) in rheumatoid arthritis (RA)
      is used as a surrogate for measure of quality of care, but the association of
      this documentation with radiographic outcomes is uncertain. We examined
      documentation of RA QMs, for disease activity and functional status and the
      association with radiographic outcomes. METHODS: Data were analyzed for 438 RA
      patients in a longitudinal cohort with complete data on van der Heijde-modified
      Total Sharp Score (TSS). All rheumatologist (N = 18) notes in the electronic
      medical record during a 24-month period were reviewed for RA QMs. Any mention of
      disease activity categorized as low, moderate, or high was considered
      documentation of the QM for disease activity. Functional status QM documentation
      included any mention of the impact of RA on function. Change in TSS was
      quantified with progression defined as >=1 unit per year. We compared percent of
      visits with an RA QM documented and mean change in TSS. RESULTS: The mean age in
      the cohort was 56.9 years, disease duration was 10.8 years, baseline DAS28 score
      was 3.8 (+/-1.6), 67.7% were seropositive, and 33.9% used a biologic DMARD.
      Radiographic progression was observed in 28.5%. Disease activity was documented
      for 29.0% of patient visits and functional status in 74.7%; neither had any
      significant relationship to mean TSS change (both P > 0.10). CONCLUSION: The
      documentation of RA QMs was infrequent and not associated with radiographic
      outcomes over 24 months.

PMID- 24560877
TI  - Health-related quality of life improves during one year of medical and surgical
      treatment in a European population-based inception cohort of patients with
      inflammatory bowel disease--an ECCO-EpiCom study.
AB  - BACKGROUND & AIMS: Health-related quality of life (HRQoL) is impaired in patients
      with Inflammatory Bowel Disease (IBD). The aim was prospectively to assess and
      validate the pattern of HRQoL in an unselected, population-based inception cohort
      of IBD patients from Eastern and Western Europe. METHODS: The EpiCom inception
      cohort consists of 1560 IBD patients from 31 European centres covering a
      background population of approximately 10.1 million. Patients answered the
      disease specific Short Inflammatory Bowel Disease Questionnaire (SIBDQ) and
      generic Short Form 12 (SF-12) questionnaire at diagnosis and after one year of
      follow-up. RESULTS: In total, 1079 patients were included in this study. Crohn's
      disease (CD) patients mean SIBDQ scores improved from 45.3 to 55.3 in Eastern
      Europe and from 44.9 to 53.6 in Western Europe. SIBDQ scores for ulcerative
      colitis (UC) patients improved from 44.9 to 57.4 and from 48.8 to 55.7,
      respectively. UC patients needing surgery or biologicals had lower SIBDQ scores
      before and after compared to the rest, while biological therapy improved SIBDQ
      scores in CD. CD and UC patients in both regions improved all SF-12 scores. Only
      Eastern European UC patients achieved SF-12 summary scores equal to or above the
      normal population. CONCLUSION: Medical and surgical treatment improved HRQoL
      during the first year of disease. The majority of IBD patients in both Eastern
      and Western Europe reported a positive perception of disease-specific but not
      generic HRQoL. Biological therapy improved HRQoL in CD patients, while UC
      patients in need of surgery or biological therapy experienced lower perceptions
      of HRQoL than the rest.

PMID- 24560880
TI  - Functional and structural study comparing the C-terminal amidated beta-neurotoxin
      Ts1 with its isoform Ts1-G isolated from Tityus serrulatus venom.
AB  - Mature Ts1, the main neurotoxin from Tityus serrulatus venom, has its C-terminal
      Cys amidated, while the isolated isoform of Ts1, named Ts1-G, keeps the non
      amidated Gly residue at the C-terminal region, allowing the study of the
      comparative functional importance of amidation at the C-terminal between these
      two native toxins. Voltage dependent sodium current measurements showed that the
      affinity of Ts1-G for sodium channels is smaller than that of the mature Ts1,
      confirming the important role played by the C-terminal amidation in determining
      Ts1 activity.

PMID- 24560882
TI  - Physiological role of AOX1a in photosynthesis and maintenance of cellular redox
      homeostasis under high light in Arabidopsis thaliana.
AB  - As plants are sessile, they often face high light (HL) stress that causes damage
      of the photosynthetic machinery leading to decreased photosynthesis. The
      importance of alternative oxidase (AOX) in optimizing photosynthesis is well
      documented. In the present study, the role of AOX in sustaining photosynthesis
      under HL was studied using AOX1a knockout mutants (aox1a) of Arabidopsis
      thaliana. Under growth light (GL; 50 MUmol photons m(-2) s(-1)) conditions, aox1a
      plants did not show any changes in photosynthetic parameters, NAD(P)/H redox
      ratios, or respiratory O2 uptake when compared to wild-type (WT). Upon exposure
      to HL (700 MUmol photons m(-2) s(-1)), respiratory rates did not vary between WT
      and aox1a. But, photosynthetic parameters related to photosystem II (PSII) and
      NaHCO3 dependent O2 evolution decreased, while the P700 reduction state increased
      in aox1a compared to WT. Further, under HL, the redox state of cellular NAD(P)/H
      pools increased with concomitant rise in reactive oxygen species (ROS) and
      malondialdehyde (MDA) content in aox1a compared to WT. In presence of HL, the
      transcript levels of several genes related to antioxidant, malate-oxaloacetate
      (malate-OAA) shuttle, photorespiratory and respiratory enzymes was higher in
      aox1a compared to WT. Taken together, these results demonstrate that under HL, in
      spite of significant increase in transcript levels of several genes mentioned
      above to maintain cellular redox homeostasis and minimize ROS production,
      Arabidopsis plants deficient in AOX1a were unable to sustain photosynthesis as is
      the case in WT plants. 

PMID- 24560881
TI  - Abnormal partitioning of hexokinase 1 suggests disruption of a glutamate
      transport protein complex in schizophrenia.
AB  - Excitatory amino acid transporter 2 (EAAT2) belongs to a family of Na(+)
      dependent glutamate transporters that maintain a low synaptic concentration of
      glutamate by removing glutamate from the synaptic cleft into astroglia and
      neurons. EAAT2 activity depends on Na(+) and K(+) gradients generated by
      Na(+)/K(+) ATPase and ATP. Hexokinase 1 (HK1), an initial enzyme of glycolysis,
      binds to mitochondrial outer membrane where it couples cytosolic glycolysis to
      mitochondrial oxidative phosphorylation, producing ATP utilized by the
      EAAT2/Na(+)/K(+) ATPase protein complex to facilitate glutamate reuptake. In this
      study, we hypothesized that the protein complex formed by EAAT2, Na(+)/K(+)
      ATPase and mitochondrial proteins in human postmortem prefrontal cortex may be
      disrupted, leading to abnormal glutamate transmission in schizophrenia. We first
      determined that EAAT2, Na(+)/K(+) ATPase, HK1 and aconitase were found in both
      EAAT2 and Na(+)/K(+) ATPase interactomes by immunoisolation and mass spectrometry
      in human postmortem prefrontal cortex. Next, we measured levels of glutamate
      transport complex proteins in subcellular fractions in the dorsolateral
      prefrontal cortex and found increases in the EAAT2B isoform of EAAT2 in a
      fraction containing extrasynaptic membranes and increased aconitase 1 in a
      mitochondrial fraction. Finally, an increased ratio of HK1 protein in the
      extrasynaptic membrane/mitochondrial fraction was found in subjects with
      schizophrenia, suggesting that HK1 protein is abnormally partitioned in this
      illness. Our findings indicate that the integrity of the glutamate transport
      protein complex may be disrupted, leading to decreased perisynaptic buffering and
      reuptake of glutamate, as well as impaired energy metabolism in schizophrenia. 

PMID- 24560883
TI  - A nano-sized manganese oxide in a protein matrix as a natural water-oxidizing
      site.
AB  - The purpose of this review is to present recent advances in the structural and
      functional studies of water-oxidizing center of Photosystem II and its
      surrounding protein matrix in order to synthesize artificial catalysts for
      production of clean and efficient hydrogen fuel. 

PMID- 24560884
TI  - Controlled nail delivery of a novel lipophilic antifungal agent using various
      modern drug carrier systems as well as in vitro and ex vivo model systems.
AB  - The penetration behavior into human nails and animal hoof membranes of a novel
      antifungal agent (EV-086K) for the treatment of onychomycosis was investigated in
      this study. The new drug provides a high lipophilicity which is adverse for
      penetration into nails. Therefore, four different formulations were developed,
      with particular focus on a colloidal carrier system (CCS) due to its penetration
      enhancing properties. On the one hand, ex vivo penetration experiments on human
      nails were performed. Afterwards the human nail plates were cut by cryomicrotome
      in order to quantify the drug concentration in the dorsal, intermediate and
      ventral nail layer using high-performance liquid chromatography (HPLC) with UV
      detection. On the other hand, equine and bovine hoof membranes were used to
      determine the in vitro penetration of the drug into the acceptor compartment of
      an online diffusion cell coupled with Fourier transform infrared attenuated total
      reflectance (FTIR-ATR) spectroscopy. In combination, both results should exhibit
      a correlation between the EV-086K penetration behavior in human nail plates and
      animal hoof membranes. The investigations showed that the developed CCS could
      increase drug delivery through the human nail most compared to other formulations
      (nail lacquer, solution and hydrogel). Using animal hooves in the online
      diffusion cell, we were able to calculate pharmacokinetic data of the penetration
      process, especially diffusion and permeability coefficients. Finally, a
      qualitative correlation between the penetration results of human nails and equine
      hooves was established. 

PMID- 24560885
TI  - Psoriasis pathogenesis - Pso p27 is generated from SCCA1 with chymase.
AB  - Psoriasis is a chronic inflammatory skin disease with unknown aetiology.
      Infiltration of inflammatory cells as the initial event in the development of new
      psoriatic plaques together with the defined inflamed areas of such lesions argues
      for an immunological disease with a local production of a causal antigen. The
      auto-antigen Pso p27 is a protein expressed in the skin lesions. We recently
      demonstrated that Pso p27 is homologous to the core amino acid sequences of
      squamous cell carcinoma antigens 1 and 2 (SCCA1/2) and it is apparently generated
      from SCCA molecules by digestion with highly specific endoproteases. In this
      communication we demonstrate the generation of Pso p27 from SCCA1 with extracts
      from psoriatic scale and even more remarkably, the generation of Pso p27 from
      SCCA1 in the presence of mast cell associated chymase. These findings open up for
      new therapeutic strategies in psoriasis and probably also in other autoimmune
      diseases as Pso p27 epitopes have been detected in diseased tissues from patients
      with various chronic inflammatory diseases. 

PMID- 24560886
TI  - Oligometastasis as a predictor for occult disease.
AB  - Oligometastasis can be defined as a state of limited metastases that is
      potentially amenable to ablative local therapy; the success of such therapy
      depends on whether or not additional occult metastases exist. A model is
      presented here to predict occult metastases given detectable oligometastases.
      Predictions were based on Bayes' theorem, in conjunction with descriptions of the
      statistical distributions for the sizes and numbers of hematogenous metastases.
      The background probability for occult metastases in individuals with
      oligometastases increased markedly with relatively minor increases in metastatic
      potential. With each additional metastasis detected the chance of further occult
      metastases increased. These latter increases were incremental and proportionately
      smaller with the more metastatic tumors. Long disease free intervals had a major
      effect to decrease in the probability of further occult disease. Demonstration of
      oligometastases depends heavily upon the sensitivity of radiological imaging
      techniques, where the proportion of detectable metastases relates to the position
      of the distribution of metastasis growth times with respect to the detection
      threshold. Given the limitations of radiological methods, and the possibility
      that the oligometastases detected may be the only disease, an aggressive approach
      appears indicated. 

PMID- 24560887
TI  - Clear cell sarcoma of soft tissue: a retrospective review and analysis of 31
      cases treated at Istituto Ortopedico Rizzoli.
AB  - INTRODUCTION: Clear cell sarcoma (CCS) of soft tissue is a rare melanocytic soft
      tissue sarcoma with different cytogenetic and natural history than that of
      melanoma. Objective of this study was to determine outcome predictors in patients
      treated in our Institute. This objective included the effectiveness of surgical
      intervention and disease progression after surgery. MATERIALS AND METHODS: Thirty
      one patients were diagnosed at our institute with clear cell sarcoma through
      tissue pathology and immunohistochemistry. Patients received multimodality
      treatment (surgery, radiotherapy and chemotherapy). Five-year survival rates and
      prognostic predictors were determined. RESULTS: Sixteen patients were males and
      15 females with a median age of 37 years (8-72-years). Twenty-eight tumors were
      located in extremities and 3 in the trunk area. Eight patients had metastases at
      their first presentation (6 local lymph nodes and 2 pulmonary metastases). Five
      and ten-year disease-specific survival rates were 56% and 41%. Two-year disease
      specific survival rates for lymph node and pulmonary metastasis groups were 40%
      and 0%. All metastatic patients died within 5 years follow-up. Five and ten-year
      disease-specific survival rates for localized tumor cases were 72% and 53%. Male
      gender, less than 30-years of age, trunk tumor location and size greater than 5
      cm were poor prognostic factors according to univariate analysis. Tumor location
      in the trunk was the only negative prognostic determinant in multivariate model.
      CONCLUSIONS: Although surgical treatment may be beneficial for tumors without
      systemic involvement, new chemotherapeutic agents and molecular targeted therapy
      should be implemented to improve the oncologic outcome in both early and late
      stage disease.

PMID- 24560889
TI  - Beneficial effects of estrogens in the brain and cardiovascular system.

PMID- 24560888
TI  - Differential effects of low-phenylalanine protein sources on brain
      neurotransmitters and behavior in C57Bl/6-Pah(enu2) mice.
AB  - Phenylketonuria (PKU) is an inborn error of metabolism caused by a deficiency of
      the enzyme phenylalanine hydroxylase, which metabolizes phenylalanine (phe) to
      tyrosine. A low-phe diet plus amino acid (AA) formula is necessary to prevent
      cognitive impairment; glycomacropeptide (GMP) contains minimal phe and provides a
      palatable alternative to the AA formula. Our objective was to assess
      neurotransmitter concentrations in the brain and the behavioral phenotype of PKU
      mice (Pah(enu2) on the C57Bl/6 background) and how this is affected by low-phe
      protein sources. Wild type (WT) and PKU mice, both male and female, were fed high
      phe casein, low-phe AA, or low-phe GMP diets between 3 and 18 weeks of age.
      Behavioral phenotype was assessed using the open field and marble burying tests,
      and brain neurotransmitter concentrations were measured using HPLC with
      electrochemical detection system. Data were analyzed by 3-way ANOVA with
      genotype, sex, and diet as the main treatment effects. Brain mass and the
      concentrations of catecholamines and serotonin were reduced in PKU mice compared
      to WT mice; the low-phe AA and GMP diets improved these parameters in PKU mice.
      Relative brain mass was increased in female PKU mice fed the GMP diet compared to
      the AA diet. PKU mice exhibited hyperactivity and impaired vertical exploration
      compared to their WT littermates during the open field test. Regardless of
      genotype or diet, female mice demonstrated increased vertical activity time and
      increased total ambulatory and horizontal activity counts compared with male
      mice. PKU mice fed the high-phe casein diet buried significantly fewer marbles
      than WT control mice fed casein; this was normalized in PKU mice fed the low-phe
      AA and GMP diets. In summary, C57Bl/6-Pah(enu2) mice showed an impaired
      behavioral phenotype and reduced brain neurotransmitter concentrations that were
      improved by the low-phe AA or GMP diets. These data support lifelong adherence to
      a low-phe diet for PKU.

PMID- 24560891
TI  - Renal transplant failure and disenfranchised grief: participants' experiences in
      the first year post-graft failure--a qualitative longitudinal study.
AB  - BACKGROUND: Renal transplant failure has a devastating impact on patients and
      their families. However, little research has been conducted in this area, which
      limits insight and understanding of the transplant failure experience that could
      subsequently inform clinical practice. OBJECTIVES: To explore participants'
      experiences of renal transplant failure in the first year post-graft failure.
      DESIGN: A qualitative, longitudinal study informed by Heideggerian hermeneutics.
      PARTICIPANTS AND SETTINGS: A purposive sample of 16 participants (8 recipients, 8
      'significant others') from a regional renal transplant unit and 3 District
      General Hospitals in South-West England. METHODS: Data were collected through a
      series of three recorded, semi-structured interviews in the first year post-renal
      transplant failure. Data analysis was informed by a three-step analytical
      process. RESULTS: Renal transplantation was the treatment of choice and had a
      transformative effect on the lives of all participants. Graft failure has 2
      distinct phases; failing and failed and the transition from one phase to the
      other is unpredictable, uncertain and stressful. Transplant failure had a
      devastating impact on all participants, regardless of time since transplantation
      and resulted in feelings of shock, grief, loss, anger, guilt and depression.
      Dialysis was disruptive and demanding and served as a constant reminder of
      transplant failure and lost freedom. Participants grieved the loss of their
      'previous life' and 'imagined future' but, beyond the understanding of close
      family members, these losses appeared unrecognised, particularly by health
      professionals. Participants used various coping mechanisms to deal with stressors
      associated with transplant failure. Factors affecting coping and adjusting
      included improved physical health and social support, which was especially
      important within the marital dyad. Healthcare services were positively evaluated,
      although information concerning the prospect of transplant failure and support
      post-graft failure could be improved. CONCLUSION: Renal transplant failure has a
      profound impact on recipients, spouses and other close family members and appears
      to resemble a form of disenfranchised grief. The theory of disenfranchised grief
      provides a coherent explication of participants' experiences in this study, which
      should help inform clinical practice, particularly in relation to the provision
      of information and emotional support post-graft failure.

PMID- 24560890
TI  - Sexually dimorphic role of G protein-coupled estrogen receptor (GPER) in
      modulating energy homeostasis.
AB  - This article is part of a Special Issue "Energy Balance". The classical estrogen
      receptors, estrogen receptor-alpha and estrogen receptor-beta are well
      established in the regulation of body weight and energy homeostasis in both male
      and female mice, whereas, the role for G protein-coupled estrogen receptor 1
      (GPER) as a modulator of energy homeostasis remains controversial. This study
      sought to determine whether gene deletion of GPER (GPER KO) alters body weight,
      body adiposity, food intake, and energy homeostasis in both males and females.
      Male mice lacking GPER developed moderate obesity and larger adipocyte size
      beginning at 8 weeks of age, with significant reductions in energy expenditure,
      but not food intake or adipocyte number. Female GPER KO mice developed increased
      body weight relative to WT females a full 6 weeks later than the male GPER KO
      mice. Female GPER KO mice also had reductions in energy expenditure, but no
      significant increases in body fat content. Consistent with their decrease in
      energy expenditure, GPER KO males and females showed significant reductions in
      two brown fat thermogenic proteins. GPER KO females, prior to their divergence in
      body weight, were less sensitive than WT females to the feeding-inhibitory
      effects of leptin and CCK. Additionally, body weight was not as modulated by
      ovariectomy or estradiol replacement in GPER KO mice. Estradiol treatment
      activated phosphorylated extracellular signal-regulated kinase (pERK) in WT but
      not GPER KO females. For the first time, GPER expression was found in the
      adipocyte but not the stromal fraction of adipose tissue. Together, these results
      provide new information elucidating a sexual dimorphism in GPER function in the
      development of postpubertal energy balance.

PMID- 24560892
TI  - Neuronal process structure and growth proteins are targets of heavy PTM
      regulation during brain development.
AB  - Brain development is a process requiring precise control of many different cell
      types. One method to achieve this is through specific and temporally regulated
      modification of proteins in order to alter structure and function. Post
      translational modification (PTM) of proteins is known to have wide-ranging and
      substantial effects on cellular function, both as part of signalling network
      modulation and more directly by modifying the function of key proteins. In this
      study, we show that PTM regulation is differentially targeted at different areas
      of the proteome, and that cytoskeletal proteins involved in neuronal process
      extension and maintenance are both more heavily modified and more frequently
      regulated at a PTM level. This suggests a clear role not only for PTMs in these
      processes, but possibly also for heavy protein modification in general.
      BIOLOGICAL SIGNIFICANCE: This study provides one of the most comprehensive sets
      of individual PTM site regulation data for mammalian brain tissue. This will
      provide a valuable resource for those wishing to perform comparisons or meta
      analyses of large scale PTMomic data, as are becoming increasingly common.
      Furthermore, being focussed on protein-level events, this study also provides
      significant insight into detailed roles for individual modified proteins in the
      developing brain, helping to advance the understanding of the complex protein
      driven processes that underlie development. Finally, the use of a novel
      bioinformatic analytical tool provides information regarding aspects of the
      PTMome which are not normally examined, and illuminates the role of PTMs on a
      more detailed, protein-centric and site-specific level in a biological context.
      The widespread yet uneven distributions observed will be relevant to those
      readers with an interest in the mechanisms of distribution of PTMS and their
      functions.

PMID- 24560893
TI  - Endocrine emergencies in pregnancy.

PMID- 24560894
TI  - Effects of airway surface liquid pH on host defense in cystic fibrosis.
AB  - Cystic fibrosis is a lethal genetic disorder characterized by viscous mucus and
      bacterial colonization of the airways. Airway surface liquid represents a first
      line of pulmonary defense. Studies in humans and animal models of cystic fibrosis
      indicate that the pH of airway surface liquid is reduced in the absence of cystic
      fibrosis transmembrane conductance regulator function. Many aspects of the innate
      host defense system of the airways are pH sensitive, including antimicrobial
      peptide/protein activity, the rheological properties of secreted mucins,
      mucociliary clearance, and the activity of proteases. This review will focus on
      how changes in airway surface liquid pH may contribute to the host defense defect
      in cystic fibrosis soon after birth. Understanding how changes in pH impact
      mucosal immunity may lead to new therapies that can modify the airway surface
      liquid environment, improve airway defenses, and alter the disease course.

PMID- 24560896
TI  - FGB mutations leading to congenital quantitative fibrinogen deficiencies: an
      update and report of four novel mutations.
AB  - INTRODUCTION: Causative mutations leading to congenital quantitative fibrinogen
      are frequently clustered in FGA encoding the fibrinogen Aalpha-chain. Mutations
      of FGB encoding the Bbeta-chain are less common and of interest since the Bbeta
      chain is considered the rate-limiting factor in the hepatic production of the
      fibrinogen hexamer. METHOD: Four novel FGB mutations were identified in two
      afibrinogenemic (one new-born and one 30 years old male) and hypofibrinogenemic
      (a 49 years old female) patient, with heterogeneous thrombotic and bleeding
      phenotype. The human fibrinogen beta chain precursor protein sequence (P02675)
      was obtained from the UniProt database. The resulting models were analysed in
      SwissPdbViewer 4.1 and POV-Ray 3.7. RESULTS: The FGB c.895T>C p.Y299H (numbering
      from the initiator Met) and the FGB c.1415G>T p.G472V were predicted to be
      deleterious by SIFT analysis. The first replaces an uncharged aromatic amino acid
      side chain by a positively charged side chain modifying the balance in the
      distribution of hydrophobic and hydrophilic of the 10 A neighbourhood residues.
      The second replaces one non-charged aliphatic side chain by another without any
      changes for the 10 A surrounding region. The FGB c.352C>T p.Q118X leads to a
      severe premature termination codon and the FGB intron 4: IVS4-1G>C (c719-1G>C)
      leads to skipping of exon 5 or usage of a cryptic acceptor site located upstream
      or downstream of the normal site. CONCLUSIONS: The continuous characterization of
      novel molecular defects responsible for fibrinogen deficiency combined with
      modelling of mutant proteins will continue to provide a better comprehension of
      the complexity of fibrinogen synthesis and physiology.

PMID- 24560895
TI  - Molecular cloning and characterization of rhesus monkey platelet glycoprotein
      Ibalpha, a major ligand-binding subunit of GPIb-IX-V complex.
AB  - INTRODUCTION: Through binding to von Willebrand factor (VWF), platelet
      glycoprotein (GP) Ibalpha, the major ligand-binding subunit of the GPIb-IX-V
      complex, initiates platelet adhesion and aggregation in response to exposed VWF
      or elevated fluid-shear stress. There is little data regarding non-human primate
      platelet GPIbalpha. This study cloned and characterized rhesus monkey (Macaca
      Mullatta) platelet GPIbalpha. MATERIALS AND METHODS: DNAMAN software was used for
      sequence analysis and alignment. N/O-glycosylation sites and 3-D structure
      modelling were predicted by online OGPET v1.0, NetOGlyc 1.0 Server and SWISS
      MODEL, respectively. Platelet function was evaluated by ADP- or ristocetin
      induced platelet aggregation. RESULTS: Rhesus monkey GPIbalpha contains 2,268
      nucleotides with an open reading frame encoding 755 amino acids. Rhesus monkey
      GPIbalpha nucleotide and protein sequences share 93.27% and 89.20% homology
      respectively, with human. Sequences encoding the leucine-rich repeats of rhesus
      monkey GPIbalpha share strong similarity with human, whereas PEST sequences and
      N/O-glycosylated residues vary. The GPIbalpha-binding residues for thrombin,
      filamin A and 14-3-3zeta are highly conserved between rhesus monkey and human.
      Platelet function analysis revealed monkey and human platelets respond similarly
      to ADP, but rhesus monkey platelets failed to respond to low doses of ristocetin
      where human platelets achieved 76% aggregation. However, monkey platelets
      aggregated in response to higher ristocetin doses. CONCLUSIONS: Monkey GPIbalpha
      shares strong homology with human GPIbalpha, however there are some differences
      in rhesus monkey platelet activation through GPIbalpha engagement, which need to
      be considered when using rhesus monkey platelet to investigate platelet GPIbalpha
      function.

PMID- 24560897
TI  - Increased adhesive properties of neutrophils and inflammatory markers in venous
      thromboembolism patients with residual vein occlusion and high D-dimer levels.
AB  - BACKGROUND: Venous thromboembolism (VTE) develops via a multicellular process on
      the endothelial surface. Although widely recognized, the relationship between
      inflammation and thrombosis, this relationship has been mostly explored in
      clinical studies by measuring circulating levels of inflammatory cytokines.
      However, the role of inflammatory cells, such as neutrophils, in the pathogenesis
      of VTE is not clear in humans. AIMS: To evaluate the adhesive properties of
      neutrophils, erythrocytes and platelets in VTE patients and to correlate findings
      with inflammatory and hypercoagulability marker levels. METHODS: Study group
      consisted of twenty-nine VTE patients and controls matched according to age,
      gender and ethnic background. Adhesive properties of neutrophils, erythrocytes
      and platelets were determined using a static adhesion assay. Neutrophil adhesion
      molecules expressions were evaluated by flow cytometry. Inflammatory and
      hypercoagulability marker levels were evaluated by standard methods. Residual
      vein occlusion (RVO) was evaluated by Doppler ultrasound. RESULTS: No significant
      difference could be observed in platelet and erythrocyte adhesion between VTE
      patients and controls. Interestingly, VTE patients with high levels of D-dimer
      and RVO, demonstrated a significant increase in neutrophil adhesion, compared to
      controls and remaining patients. Inflammatory markers (IL-6, IL-8, TNF-alpha)
      were also significantly elevated in this subgroup, compared to other VTE
      patients. Adhesive properties of neutrophils correlated with IL-6 and D-dimer
      levels. Neutrophils adhesion molecules (CD11a, CD11b and CD18) were not altered
      in any of the groups. CONCLUSION: These findings not only support the hypothesis
      of an association between inflammation and hypercoagulability, but more
      importantly, highlight the role of neutrophils in this process.

PMID- 24560898
TI  - Prostatic artery embolization to treat lower urinary tract symptoms related to
      benign prostatic hyperplasia and bleeding in patients with prostate cancer:
      proceedings from a multidisciplinary research consensus panel.

PMID- 24560899
TI  - Mild hypoxia affects synaptic connectivity in cultured neuronal networks.
AB  - Eighty percent of patients with chronic mild cerebral ischemia/hypoxia resulting
      from chronic heart failure or pulmonary disease have cognitive impairment. Overt
      structural neuronal damage is lacking and the precise cause of neuronal damage is
      unclear. As almost half of the cerebral energy consumption is used for synaptic
      transmission, and synaptic failure is the first abrupt consequence of acute
      complete anoxia, synaptic dysfunction is a candidate mechanism for the cognitive
      deterioration in chronic mild ischemia/hypoxia. Because measurement of synaptic
      functioning in patients is problematic, we use cultured networks of cortical
      neurons from new born rats, grown over a multi-electrode array, as a model
      system. These were exposed to partial hypoxia (partial oxygen pressure of 150Torr
      lowered to 40-50Torr) during 3 (n=14) or 6 (n=8) hours. Synaptic functioning was
      assessed before, during, and after hypoxia by assessment of spontaneous network
      activity, functional connectivity, and synaptically driven network responses to
      electrical stimulation. Action potential heights and shapes and non-synaptic
      stimulus responses were used as measures of individual neuronal integrity. During
      hypoxia of 3 and 6h, there was a statistically significant decrease of
      spontaneous network activity, functional connectivity, and synaptically driven
      network responses, whereas direct responses and action potentials remained
      unchanged. These changes were largely reversible. Our results indicate that in
      cultured neuronal networks, partial hypoxia during 3 or 6h causes isolated
      disturbances of synaptic connectivity. 

PMID- 24560900
TI  - Influences of hyperthermia-induced seizures on learning, memory and
      phosphorylative state of CaMKIIalpha in rat hippocampus.
AB  - Febrile seizure (FS) remains the most common childhood neurological emergency.
      Although many studies have been done, controversy exists as to whether these
      seizures are associated with a significant risk for cognitive impairment. The aim
      of our study is to check whether there is a spatial learning and memory deficit
      in the experimental FS rats using a heated-air FS paradigm and to determine the
      possible molecular mechanism of cognitive impairment. On days 10 to 12
      postpartum, the male rat pups were subjected to one, three, or nine episodes of
      brief hyperthermia-induced seizures (HS). At adolescence and adulthood, the rats
      subjected to three, or nine episodes of HS had significant deficits in spatial
      learning and memory tested by Morris water maze. At adulthood, no apparent
      hippocampal neuronal loss was found in any HS group, but the seizure threshold to
      flurothyl was decreased significantly in the rats subjected to nine episodes of
      HS. In the rats subjected to three, or nine episodes of HS, the Western
      immunoblotting showed that there was a significant translocation of Ca(2+)
      calmodulin stimulated protein kinase II (CaMKII) from the postsynaptic density to
      the cytosol. In the postsynaptic density the phosphorylation of CaMKIIalpha
      Thr(286) was reduced significantly, but the phosphorylation of CaMKIIalpha
      Thr(305) was increased significantly. Our study showed early-life brief but
      recurrent HS caused long-term cognitive impairment and CaMKIIalpha was involved
      in carrying forward the signal resulting from HS. The change of the
      phosphorylative level in Thr(286) and Thr(305) sites of CaMKIIalpha may underlie
      the molecular mechanism for the HS related cognitive impairment. 

PMID- 24560901
TI  - Inhibitory modulation of CART peptides in accumbal neuron through decreasing
      interaction of CaMKIIalpha with dopamine D3 receptors.
AB  - Previous studies in rats have shown that microinjections of cocaine- and
      amphetamine-regulated transcript (CART) peptide into the nucleus accumbens (NAc;
      the area of the brain that mediates drug reward and reinforcement) attenuate the
      locomotor effects of psychostimulants. CART peptide has also been shown to induce
      decreased intracellular concentrations of calcium (Ca(2+)) in primary cultures of
      hippocampus neurons. The purpose of this study was to characterize the
      interaction of Ca(2+)/calmodulin-dependent kinases (CaMKIIalpha) with dopamine D3
      (D3) receptors (R) in primary cultures of accumbal neurons. This interaction is
      involved in inhibitory modulation of CART peptides. In vitro, CART (55-102)
      peptide (0.1, 0.5 or 1MUM) was found to dose-dependently inhibit K(+)
      depolarization-elicited Ca(2+) influx and CaMKIIalpha phosphorylation in accumbal
      neurons. Moreover, CART peptides were also found to block cocaine (1MUM)-induced
      Ca(2+) influx, CaMKIIalpha phosphorylation, CaMKIIalpha-D3R interaction, and CREB
      phosphorylation. In vivo, repeated microinjections of CART (55-102) peptide
      (2MUg/1MUl/side) into the NAc over a 5-day period had no effect on behavioral
      activity but blocked cocaine-induced locomotor activity. These results indicate
      that D3R function in accumbal neurons is a target of CART (55-102) peptide and
      suggest that CART peptide by dephosphorylating limbic D3Rs may have potential as
      a treatment for cocaine abuse. 

PMID- 24560902
TI  - Ligustilide prevents the apoptosis effects of tumour necrosis factor-alpha during
      C2C12 cell differentiation.
AB  - Ligustilide, the major component of Angelica sinensis, is also thought to be the
      most potent bioactive constituent of this plant. Ligustilide has been reported to
      markedly protect neural tissue against apoptosis. However, little is known
      regarding ligustilide's anti-apoptosis effect in muscle tissue. The aim of the
      study was to investigate the anti-apoptosis effects of ligustilide on TNF-alpha
      induced C2C12 cells during differentiation. It was revealed that ligustilide at
      various concentrations significantly prevented the apoptosis of C2C12 cells
      incubated in TNF-alpha as assessed by apoptosis index and DNA fragmentation.
      Moreover, ligustilide-treated groups exhibited a significant increase in the bcl
      2/bax ratio, pro-caspase 3 and pro-caspase 8 compared with the TNF-alpha-control
      group in a dose-dependent manner. Meanwhile, ligustilide-treated groups presented
      a significantly increased level of phosphorylated Akt and suppressed expression
      of the myogenin protein. Therefore, the findings derived suggested that
      ligustilide protected C2C12 cells from TNF-alpha-induced apoptosis during
      differentiation by reducing apoptosis and inducing cell proliferation. 

PMID- 24560903
TI  - Protective effect of tormentic acid from Potentilla chinensis against
      lipopolysaccharide/D-galactosamine induced fulminant hepatic failure in mice.
AB  - A compound was isolated from Potentilla chinensis, and it was identified as
      tormentic acid (TA) based on its physicochemical properties and spectral data.
      The hepatoprotective effect of TA was evaluated using an acute liver failure
      model induced by lipopolysaccharide (LPS)/D-galactosamine (D-GalN). The results
      revealed that TA significantly prevented LPS/D-GalN-induced fulminant hepatic
      failure, as evidenced by the decrease in serum aminotransferase and total
      bilirubin activities and the attenuation of histopathological changes. TA
      alleviated the pro-inflammatory cytokines including TNF-alpha and NO/iNOS by
      inhibiting nuclear factor-kappaB (NF-kappaB) activity. Moreover, TA strongly
      inhibited lipid peroxidation, recruited the anti-oxidative defense system, and
      increased HO-1 activity. In addition, TA significantly attenuated increases in
      TUNEL-positive hepatocytes through decreasing the levels of cytochrome c, as well
      as caspases-3, 8 and 9, while augmenting the expression of Bcl-2. In conclusion,
      TA protects hepatocytes against LPS/D-GalN-induced injury by blocking NF-kappaB
      signaling pathway for anti-inflammatory response and attenuating hepatocellular
      apoptosis. Consequently, TA is a potential agent for preventing acute liver
      injury and may be a major bioactive ingredient of Potentilla chinensis.

PMID- 24560904
TI  - Pharmacological preconditioning with adenosine A(1) receptor agonist suppresses
      cellular immune response by an A(2A) receptor dependent mechanism.
AB  - Under stressful conditions such as ischemia, sepsis, and severe trauma, adenosine
      levels are elevated and protect the tissue by interaction with G coupled
      receptors. In a model of peritonitis, we previously found that pharmacological
      preconditioning (PPC) of mice with a selective adenosine A1 receptor (A1R)
      agonist, 2-chloro-N(6)-cyclopentyladenosine (CCPA), induced the A2AR which
      reduces cytokine secretion and leukocyte recruitment. In our present study we
      determined whether mice PPC will moderate cellular immune response by the same
      mechanism. Similar to the effect on inflammation, PPC reduced the response to
      lymphocyte mitogens and allogeneic MLR response. The inhibitory effect of PPC on
      the immune response was A1R and A2AR dependent as illustrated by experiments with
      antagonists of these receptors and mice with knock down (KO) receptors. In MLR
      with PPC splenocytes we found reduced levels of pro-inflammatory cytokines (IFN
      gamma, IL-15, TNF-alpha) and elevation of IL-10, as well as elevation of
      regulatory T-cell. Our data indicate that PPC is able to remarkably suppress
      cellular immune response due to the sensitization A2AR. This effect of PPC sheds
      light on the protective role of adenosine in ischemic preconditioning and makes
      this treatment candidate for the prevention of graft rejection. 

PMID- 24560905
TI  - Protective effects of garcinol in mice with lipopolysaccharide/D-galactosamine
      induced apoptotic liver injury.
AB  - Garcinol is a polyisoprenylated benzophenone derivative of Garcinia indica.
      Recent researches have revealed the antioxidant, anticancer and anti-inflammatory
      properties of garcinol. In the present study, the pharmacological effects of
      garcinol in lipopolysaccharide (LPS)-induced hepatic injury in D-galactosamine (D
      Gal)-sensitized mice were investigated. We found that treatment with garcinol
      significantly decreased serum ALT and AST levels in LPS/D-Gal-exposed mice. These
      were accomplished with improved histological alterations in liver sections and
      reduced malondialdehyde (MDA) content in liver homogenates. Garcinol
      significantly reduced the acetylation level of NF-kappaB, but it had no obvious
      effects on the elevation of TNF-alpha or IL-6 in plasma or liver tissue. Garcinol
      significantly attenuated LPS/D-Gal-induced hepatic apoptosis as evidenced by
      reduced number of TUNEL-positive cells in liver sections. Our experiments also
      showed that garcinol markedly suppressed the cleavage of caspase-3 and
      significantly decreased the activities of caspase-3, -8, and -9 in liver tissues.
      In addition, garcinol obviously reduced the induction of Bax but did not alter
      the level of Bcl-2. These results indicated that garcinol might provide
      protective benefits in LPS/D-Gal-induced liver injury through suppressing
      apoptosis. 

PMID- 24560906
TI  - Thymoquinone alleviates thioacetamide-induced hepatic fibrosis and inflammation
      by activating LKB1-AMPK signaling pathway in mice.
AB  - The current study was conducted to investigate the anti-fibrotic effect and its
      possible underlying mechanisms of thymoquinone (TQ) against hepatic fibrosis in
      vivo. TQ is the major active compound derived from the medicinal Nigella sativa.
      Liver fibrosis was induced in male Kunming mice by intraperitoneal injections of
      thioacetamide (TAA, 200 mg/kg). Mice were treated concurrently with TAA alone or
      TAA plus TQ (20 mg/kg or 40 mg/kg) given daily by oral gavage. Our data
      demonstrated that TQ treatment obviously reversed liver tissue damage compared
      with TAA alone group, characterized by less inflammatory infiltration and
      accumulation of extracellular matrix (ECM) proteins. TQ significantly attenuated
      TAA-induced liver fibrosis, accompanied by reduced protein and mRNA expression of
      alpha-smooth muscle actin (alpha-SMA), collagen-I and tissue inhibitor of
      metalloproteinase-1 (TIMP-1). TQ downregulated the expression of toll-like
      receptor 4 (TLR4) and remarkably decreased proinflammatory cytokine levels as
      well. TQ also significantly inhibited phosphatidylinositol 3-kinase (PI3K)
      phosphorylation. Furthermore, TQ enhanced the phosphorylation adenosine
      monophosphate-activated protein kinase (AMPK) and liver kinase B (LKB)-1. In
      conclusion, TQ may reduce ECM accumulation, and it may be at least regulated by
      phosphorylation of AMPK signaling pathways, suggesting that TQ may be a potential
      candidate for the therapy of hepatic fibrosis.

PMID- 24560907
TI  - Arthroscopic versus open shoulder stabilization: current practice patterns in the
      United States.
AB  - PURPOSE: The purpose of this study was to investigate current trends in
      arthroscopic and open shoulder stabilization in the United States. METHODS:
      Patients who underwent arthroscopic shoulder stabilization (Current Procedural
      Terminology code 29806) or open stabilization (Current Procedural Terminology
      codes 23455 [open Bankart repair], 23460 [anterior bone block], and 23462
      [coracoid transfer]) were identified using a national database of insurance
      billing records during the years 2004 through 2009. Demographic data were
      recorded for each patient. RESULTS: From 2004 through 2009, there were 23,096
      cases of shoulder stabilization, of which 84% (19,337) were arthroscopic and 16%
      (3,759) were open procedures. There were 17,241 male patients (75%) and 5,855
      female patients (25%). The incidence of arthroscopic shoulder stabilization
      nearly doubled during the period studied, increasing from 11.8 cases for every
      10,000 patients in 2004 to 22.9 cases for every 10,000 patients in 2009. The
      percentage of arthroscopic stabilizations increased from 71% of stabilization
      procedures in 2004 to 89% in 2009, whereas the percentage of open stabilizations
      decreased from 29% in 2004 to 11% in 2009 (P < .0001). Among open procedures, a
      significant decline in the incidence of open Bankart repair was observed, from
      4.5 cases for every 10,000 patients in 2004 to 2.2 cases for every 10,000
      patients in 2009 (P < .0001), whereas the performance of open coracoid transfer
      increased from 0.17 cases per 10,000 patients in 2004 to 0.40 cases per 10,000
      patients in 2009 (P < .0001). For both arthroscopic and open stabilization, the
      group aged 10 to 19 years had the highest rate of surgery (29%), followed by the
      group aged 20 to 29 years (25%). CONCLUSIONS: The current data indicate that
      arthroscopic stabilization is performed in nearly 90% of shoulder stabilization
      surgeries and nearly doubled in incidence from 2004 to 2009 in the United States.
      Additional research is needed to further investigate the long-term clinical
      outcomes of this practice pattern. LEVEL OF EVIDENCE: Level IV, retrospective
      database review.

PMID- 24560908
TI  - Variability in locations of hip neurovascular structures and their proximity to
      hip arthroscopic portals.
AB  - PURPOSE: To measure the distances of pertinent neurovascular structures from bony
      landmarks used during hip arthroscopy and compare them among different
      demographic groups. METHODS: The distances from neurovascular structures to bony
      landmarks often used during hip arthroscopy were measured on magnetic resonance
      images of the hip in 100 patients. The structures studied include the lateral
      femoral cutaneous nerve (LFCN), sciatic nerve, femoral nerve, and femoral artery.
      These distances were then compared across different demographic groups, and
      statistical analysis was performed. RESULTS: The mean anteroposterior (AP)
      distance from the tip of the greater trochanter to the sciatic nerve was 10.32 mm
      (range, 0 to 23.8 mm). At the level of the superior tip of the greater
      trochanter, the mean distances from the anterior superior iliac spine reference
      line to the LFCN, femoral nerve, and femoral artery were 6.37 mm (range, -9.8 to
      35.9 mm) for medial-lateral, 23.24 mm (range, 3.4 to 67.0 mm) for AP, and 26.34
      mm (range, 7.3 to 65.5 mm) for AP, respectively. We found significant differences
      in distances for the LFCN, femoral nerve, and femoral artery for weight (P =
      .003, P = .041, and P = .004, respectively) and body mass index (P = .003, P =
      .010, and P = .003, respectively), as well as for the LFCN between whites and
      Hispanics (P = .032). There were also significant differences for the femoral
      nerve vector between African Americans and whites (P = .04), as well as between
      African Americans and Hispanics (P = .04). CONCLUSIONS: We found the LFCN to be
      the most at-risk neurovascular structure with hip arthroscopy portal placement.
      This study also showed that there is wide variability in the locations of
      pertinent neurovascular structures across different demographic groups, including
      weight, body mass index, and race or ethnicity. CLINICAL RELEVANCE: Portal
      placement during hip arthroscopy carries a risk of neurovascular injury,
      particularly to the LFCN. The clinician should be aware of the variability in
      structure location with different patient demographic characteristics.

PMID- 24560910
TI  - Protective effects of ginsenoside Rg1 on chronic restraint stress induced
      learning and memory impairments in male mice.
AB  - Alzheimer's disease (AD) is one of the major neurological diseases of the
      elderly. Chronic stress, which can induce atrophy and functional impairments in
      several key brain areas such as the frontal cortex and hippocampus, plays an
      important role in the generation and progression of AD. Currently, there are no
      effective drug treatment options for preventing chronic stress induced learning
      and memory impairments and neuronal damage. Ginsenoside Rg1 (Rg1) is a steroidal
      saponin abundantly contained in ginseng. This study explored the neuroprotective
      effects of Rg1 on chronic restraint stress (CRS) induced learning and memory
      impairments in a mouse model. Our results showed that Rg1 (5mg/kg) significantly
      protected against learning and memory impairments induced by CRS in a Morris
      water maze. Besides, Rg1 (2, 5mg/kg) was able to decrease ROS generation and
      attenuate the neuronal oxidative damage in the frontal cortex and hippocampus CA1
      in mice. Additionally, the inhibition of NOX2, p47phox and RAC1 expression is
      also involved in the action mechanisms of Rg1 in this experimental model. This
      study provided an experimental basis for the clinical application of Rg1 in
      chronic stress induced neuronal oxidative damage.

PMID- 24560909
TI  - Establishment of transgenic lines to monitor and manipulate Yap/Taz-Tead activity
      in zebrafish reveals both evolutionarily conserved and divergent functions of the
      Hippo pathway.
AB  - To investigate the role of Hippo pathway signaling during vertebrate development
      transgenic zebrafish lines were generated and validated to dynamically monitor
      and manipulate Yap/Taz-Tead activity. Spatial and temporal analysis of Yap/Taz
      Tead activity suggested the importance of Hippo signaling during cardiac
      precursor migration and other developmental processes. When the transcriptional
      co-activators, Yap and Taz were restricted from interacting with DNA-binding Tead
      transcription factors through expression of a dominant negative transgene,
      cardiac precursors failed to migrate completely to the midline resulting in
      strong cardia bifida. Yap/Taz-Tead activity reporters also allowed us to
      investigate upstream and downstream factors known to regulate Hippo signaling
      output in Drosophila. While Crumbs mutations in Drosophila eye disc epithelia
      increase nuclear translocation and activity of Yorkie (the fly homolog of
      Yap/Taz), zebrafish crb2a mutants lacked nuclear Yap positive cells and down
      regulated Yap/Taz-Tead activity reporters in the eye epithelia, despite the loss
      of apical-basal cell polarity in those cells. However, as an example of
      evolutionary conservation, the Tondu-domain containing protein Vestigial-like 4b
      (Vgll4b) was found to down-regulate endogenous Yap/Taz-Tead activity in the
      retinal pigment epithelium, similar to Drosophila Tgi in imaginal discs. In
      conclusion, the Yap/Taz-Tead activity reporters revealed the dynamics of Yap/Taz
      Tead signaling and novel insights into Hippo pathway regulation for vertebrates.
      These studies highlight the utility of this transgenic tool-suite for ongoing
      analysis into the mechanisms of Hippo pathway regulation and the consequences of
      signaling output. 

PMID- 24560912
TI  - The pharmacology of the human female orgasm - its biological and physiological
      backgrounds.
AB  - The female orgasm has been examined over the years by numerous scientific
      disciplines yet it still has many secrets to be disclosed. Because its
      physiology, especially its neurophysiology, is sparingly understood its
      pharmacology is necessarily limited based mainly on the side effects of drugs.
      Few published studies have used a placebo group as controls. The paucity of
      focussed studies is well illustrated by the fact that there still is no approved
      medication to treat female orgasmic dysfunction. The present brief overview
      examines the most important aspects of its biology and especially its physiology
      highlighting the many questions that need answering if we are to have a
      comprehensive pharmacology of the female orgasm. 

PMID- 24560911
TI  - Differential effects of non-nicotine tobacco constituent compounds on nicotine
      self-administration in rats.
AB  - Tobacco smoking has been shown to be quite addictive in people. However, nicotine
      itself is a weak reinforcer compared to other commonly abused drugs, leading
      speculation that other factors contribute to the high prevalence of tobacco
      addiction in the human population. In addition to nicotine, there are over 5000
      chemical compounds that have been identified in tobacco smoke, and more work is
      needed to ascertain their potential contributions to tobacco's highly addictive
      properties, or as potential candidates for smoking cessation treatment. In this
      study, we examined seven non-nicotine tobacco constituent compounds (anabasine,
      anatabine, nornicotine, myosmine, harmane, norharmane, and tyramine) for their
      effects on nicotine self-administration behavior in rats. Young adult female
      Sprague-Dawley rats were allowed to self-administer nicotine (0.03 mg/kg/50 MUl
      infusion) under a fixed ratio-1 schedule of reinforcement. Each self
      administration session lasted 45 min. Doses of each tobacco constituent compound
      were administered subcutaneously 10 min prior to the start of each session in a
      repeated measures, counterbalanced order two times. Anabasine displayed a
      biphasic dose-effect function. Pretreatment with 0.02 mg/kg anabasine resulted in
      a 25% increase in nicotine self-administration, while 2.0mg/kg of anabasine
      reduced nicotine infusions per session by over 50%. Pretreatment with 2.0mg/kg
      anatabine also significantly reduced nicotine self-administration by nearly half.
      These results suggest that some non-nicotine tobacco constituents may enhance or
      reduce nicotine's reinforcing properties. Also, depending upon the appropriate
      dose, some of these compounds may also serve as potential smoking cessation
      agents.

PMID- 24560913
TI  - Adaptation to leftward-shifting prisms enhances local processing in healthy
      individuals.
AB  - In healthy individuals, adaptation to left-shifting prisms has been shown to
      simulate the symptoms of hemispatial neglect, including a reduction in global
      processing that approximates the local bias observed in neglect patients. The
      current study tested whether leftward prism adaptation can more specifically
      enhance local processing abilities. In three experiments, the impact of local and
      global processing was assessed through tasks that measure susceptibility to
      illusions that are known to be driven by local or global contextual effects.
      Susceptibility to the rod-and-frame illusion - an illusion disproportionately
      driven by both local and global effects depending on frame size - was measured
      before and after adaptation to left- and right-shifting prisms. A significant
      increase in rod-and-frame susceptibility was found for the left-shifting prism
      group, suggesting that adaptation caused an increase in local processing effects.
      The results of a second experiment confirmed that leftward prism adaptation
      enhances local processing, as assessed with susceptibility to the simultaneous
      tilt illusion. A final experiment employed a more specific measure of the global
      effect typically associated with the rod-and-frame illusion, and found that
      although the global effect was somewhat diminished after leftward prism
      adaptation, the trend failed to reach significance (p=.078). Rightward prism
      adaptation had no significant effects on performance in any of the experiments.
      Combined, these findings indicate that leftward prism adaptation in healthy
      individuals can simulate the local processing bias of neglect patients primarily
      through an increased sensitivity to local visual cues, and confirm that prism
      adaptation not only modulates lateral shifts of attention, but also prompts
      shifts from one level of processing to another. 

PMID- 24560915
TI  - VL: a further case of erroneous recollection.
AB  - We report a single-case study of a female patient (VL) who exhibited frequent
      episodes of erroneous recollections triggered by everyday events. Based on
      neuropsychological testing, VL was classified as suffering from mild to moderate
      dementia (MMSE=18) and was given a diagnosis of probable Alzheimer's disease. Her
      memory functions were uniformly impaired but her verbal abilities were generally
      well preserved. A structural MRI scan showed extensive areas of gray matter
      atrophy particularly in frontal and medial-temporal (MTL) areas. Results of
      experimental recognition tests showed that VL had very high false alarm rates on
      tests using pictures, faces and auditory stimuli, but lower false alarm rates on
      verbal tests. We provide a speculative account of her erroneous recollections in
      terms of her MTL and frontal pathology. In outline, we suggest that owing to
      binding failures in MTL regions, VL's recognition processes were forced to rely
      on earlier than normal stages of analysis. Environmental features on a given
      recognition trial may have combined with fragments persisting from previous
      trials resulting in erroneous feelings of familiarity and of recollection that
      were not discounted or edited out, due to her impaired frontal processes.

PMID- 24560914
TI  - Multisensory convergence of visual and haptic object preference across
      development.
AB  - Visuohaptic inputs offer redundant and complementary information regarding an
      object's geometrical structure. The integration of these inputs facilitates
      object recognition in adults. While the ability to recognize objects in the
      environment both visually and haptically develops early on, the development of
      the neural mechanisms for integrating visual and haptic object shape information
      remains unknown. In the present study, we used functional Magnetic Resonance
      Imaging (fMRI) in three groups of participants, 4 to 5.5 year olds, 7 to 8.5 year
      olds, and adults. Participants were tested in a block design involving visual
      exploration of two-dimensional images of common objects and real textures, and
      haptic exploration of their three-dimensional counterparts. As in previous
      studies, object preference was defined as a greater BOLD response for objects
      than textures. The analyses specifically target two sites of known visuohaptic
      convergence in adults: the lateral occipital tactile-visual region (LOtv) and
      intraparietal sulcus (IPS). Results indicated that the LOtv is involved in
      visuohaptic object recognition early on. More importantly, object preference in
      the LOtv became increasingly visually dominant with development. Despite previous
      reports that the lateral occipital complex (LOC) is adult-like by 8 years, these
      findings indicate that at least part of the LOC is not. Whole-brain maps showed
      overlap between adults and both groups of children in the LOC. However, the
      overlap did not build incrementally from the younger to the older group,
      suggesting that visuohaptic object preference does not develop in an additive
      manner. Taken together, the results show that the development of neural
      substrates for visuohaptic recognition is protracted compared to substrates that
      are primarily visual or haptic.

PMID- 24560916
TI  - Pallial mucus of the oyster Crassostrea virginica regulates the expression of
      putative virulence genes of its pathogen Perkinsus marinus.
AB  - Perkinsus marinus is a pathogen responsible for severe mortalities of the eastern
      oyster Crassostrea virginica along the East and Gulf coasts of the United States.
      When cultivated, the pathogenicity of this microorganism decreases significantly,
      hampering the study of its virulence factors. Recent investigations have shown a
      significant increase of the in vivo virulence of P. marinus exposed to oyster
      pallial mucus. In the current study, we investigated the effect of pallial mucus
      on P. marinus gene expression compared with cultures supplemented with oyster
      digestive extracts or with un-supplemented cultures. In parallel, parasite cells
      cultured under these three conditions were used to challenge oysters and to
      assess virulence in vivo. Perkinsus marinus mRNA sequencing was performed on an
      Illumina GAIIX sequencer and data were analysed using the Tuxedo RNAseq suite for
      mapping against the draft P. marinus genome and for differential expression
      analysis. Results showed that exposure of P. marinus to mucus induces significant
      regulation of nearly 3,600 transcripts, many of which are considered as putative
      virulence factors. Pallial mucus is suspected to mimic internal host conditions,
      thereby preparing the pathogen to overcome defense factors before invasion. This
      hypothesis is supported by significant regulation in several antioxidant
      proteins, heat shock proteins, protease inhibitors and proteasome subunits. In
      addition, mucus exposure induced the modulation of several genes known to affect
      immunity and apoptosis in vertebrates and invertebrates. Several proteases
      (proteolysis) and merozoite surface proteins (cell recognition) were also
      modulated. Overall, these results provide a baseline for targeted, in depth
      analysis of candidate virulence factors in P. marinus. 

PMID- 24560917
TI  - Molecular insight into systematics, host associations, life cycles and geographic
      distribution of the nematode family Rhabdiasidae.
AB  - Rhabdiasidae Railliet, 1915 is a globally distributed group of up to 100 known
      species of nematodes parasitic in amphibians and reptiles. This work presents the
      results of a molecular phylogenetic analysis of 36 species of Rhabdiasidae from
      reptiles and amphibians from six continents. New DNA sequences encompassing
      partial 18S rDNA, ITS1, 5.8S rDNA, ITS2 and partial 28S rDNA regions of nuclear
      ribosomal DNA were obtained from 27 species and pre-existing sequences for nine
      species were incorporated. The broad taxonomic, host and geographical coverage of
      the specimens allowed us to address long-standing questions in rhabdiasid
      systematics, evolution, geographic distribution, and patterns of host
      association. Our analysis demonstrated that rhabdiasids parasitic in snakes are
      an independent genus sister to the rest of the Rhabdiasidae, a status supported
      by life cycle data. Based on the combined evidence of molecular phylogeny,
      morphology and life cycle characteristics, a new genus Serpentirhabdias gen. nov.
      with the type species Serpentirhabdias elaphe (Sharpilo, 1976) comb. nov. is
      established. The phylogeny supports the monophyly of Entomelas Travassos, 1930,
      Pneumonema Johnston, 1916 and the largest genus of the family, Rhabdias Stiles
      and Hassall, 1905. DNA sequence comparisons demonstrate the presence of more than
      one species in the previously monotypic Pneumonema from Australian scincid
      lizards. The distribution of some morphological characters in the genus Rhabdias
      shows little consistency within the phylogenetic tree topology, in particular the
      apical structures widely used in rhabdiasid systematics. Our data suggest that
      some of the characters, while valuable for species differentiation, are not
      appropriate for differentiation among higher taxa and are of limited phylogenetic
      utility. Rhabdias is the only genus with a cosmopolitan distribution, but some of
      the lineages within Rhabdias are distributed on a single continent or a group of
      adjacent zoogeographical regions. Serpentirhabdias, Entomelas and Pneumonema show
      rather strict specificity to their host groups. The evolution of the Rhabdiasidae
      clearly included multiple host switching events among different orders and
      families of amphibians as well as switching between amphibians and squamatan
      reptiles. Only a few smaller lineages of Rhabdias demonstrate relatively strict
      associations with a certain group of hosts. 

PMID- 24560918
TI  - Binding of von Willebrand factor and plasma proteins to the eggshell of
      Schistosoma mansoni.
AB  - Schistosoma mansoni eggs have to cross the endothelium and intestinal wall to
      leave the host and continue the life cycle. Mechanisms involved in this essential
      step are largely unknown. Here we describe direct binding to the S. mansoni
      eggshell of von Willebrand factor and other plasma proteins involved in
      haemostasis. Using deletion-mutants, we demonstrated that it is the A1 domain of
      von Willebrand factor that binds to the eggshell. Our results suggest that
      binding of plasma proteins to the eggshell promotes binding to the endothelium,
      initiating the passage of the egg through the blood-vessel wall to be excreted in
      the end. 

PMID- 24560919
TI  - Colistin/daptomycin: an unconventional antimicrobial combination synergistic in
      vitro against multidrug-resistant Acinetobacter baumannii.
AB  - The in vitro activity of the combination colistin/daptomycin was evaluated
      against multidrug-resistant Acinetobacter baumannii clinical isolates. Clonal
      relationships were assessed by pulsed-field gel electrophoresis. The following
      synergy studies were undertaken: (i) daptomycin MICs were determined by E-test on
      Mueller-Hinton agar plates supplemented with a subinhibitory concentration of
      colistin; and (ii) time-kill methodology using tubes containing an inoculum of
      5*10(5)CFU/mL and subinhibitory concentrations of each antibiotic alone or in
      combination subcultured at 0, 5 and 24h for colony counting. Synergy was defined
      as >=2log10CFU/mL decrease of viable colonies compared with colistin alone. Ten
      colistin-susceptible and four colistin-resistant A. baumannii isolates were
      tested. Isolates were assigned to nine different clonal types. Enhanced in vitro
      activity of the combination was detected only against colistin-susceptible
      isolates; using plates supplemented with colistin, the daptomycin MIC was reduced
      by 4- to 128-fold. From a total of 30 isolate-concentration combinations in time
      kill studies, a synergistic interaction was detected in 16 (53.3%). The
      combination exhibited synergy against 8 and 12 of these combinations at 5h and
      24h, respectively. No antagonism was detected. Colistin alone was bactericidal
      against two colistin-susceptible isolates at 24h, whereas the combination was
      bactericidal against 9 colistin-susceptible isolates at 24h. Against all colistin
      resistant isolates, the combination exhibited a static effect and indifference in
      time-kill studies. Potent in vitro synergistic interactions between colistin and
      daptomycin provide evidence that this unorthodox combination may be beneficial in
      the treatment of colistin-susceptible multidrug-resistant A. baumannii. 

PMID- 24560920
TI  - Transcatheter closure of patent ductus arteriosus: past, present and future.
AB  - This review aims to describe the past history, present techniques and future
      directions in transcatheter treatment of patent ductus arteriosus (PDA).
      Transcatheter PDA closure is the standard of care in most cases and PDA closure
      is indicated in any patient with signs of left ventricular volume overload due to
      a ductus. In cases of left-to-right PDA with severe pulmonary arterial
      hypertension, closure may be performed under specific conditions. The management
      of clinically silent or very tiny PDAs remains highly controversial. Techniques
      have evolved and the transcatheter approach to PDA closure is now feasible and
      safe with current devices. Coils and the Amplatzer Duct Occluder are used most
      frequently for PDA closure worldwide, with a high occlusion rate and few
      complications. Transcatheter PDA closure in preterm or low-bodyweight infants
      remains a highly challenging procedure and further device and catheter design
      development is indicated before transcatheter closure is the treatment of choice
      in this delicate patient population. The evolution of transcatheter PDA closure
      from just 40 years ago with 18F sheaths to device delivery via a 3F sheath is
      remarkable and it is anticipated that further improvements will result in better
      safety and efficacy of transcatheter PDA closure techniques.

PMID- 24560921
TI  - Editorial on "purification of nucleic acids using isotachophoresis", by Anita
      Rogacs, Lewis A. Marshall and Juan G. Santiago.

PMID- 24560922
TI  - Cucurbit[6]uril in combination with guanidinium ionic liquid as a new type of
      stationary phase for capillary gas chromatography.
AB  - Cucurbit[n]urils (CBs) possess unique structures and selective interactions with
      analytes of different variety and high thermal stability and show a great
      potential as stationary phases for capillary gas chromatography (GC). This work
      presents the first description of CB6 in combination with a new guanidinium-based
      ionic liquid (GBIL) as the GC stationary phase by using sol-gel coating method
      for the preparation of the CB6-GBIL and GBIL columns. Introduction of GBIL
      greatly improved the solubility of CB6 in the sol solution and successfully made
      the use of CBs for the intended purpose feasible. The CB6-GBIL and GBIL columns
      had average polarity of 179 and 280, respectively, suggesting their medium polar
      nature. The CB6-GBIL column achieves good resolution for a wide range of analytes
      and exhibits different retention behaviors and resolution for some of the
      analytes from the GBIL column and the commercial column. Moreover, it also shows
      good thermal stability up to 250 degrees C. The proposed method integrates the
      full advantages of CBs, ionic liquids and sol-gel coating method and provides an
      efficient and feasible way for the wider application of CBs in separation
      science. 

PMID- 24560923
TI  - Polyphosphate is a primordial chaperone.
AB  - Composed of up to 1,000 phospho-anhydride bond-linked phosphate monomers,
      inorganic polyphosphate (polyP) is one of the most ancient, conserved, and
      enigmatic molecules in biology. Here we demonstrate that polyP functions as a
      hitherto unrecognized chaperone. We show that polyP stabilizes proteins in vivo,
      diminishes the need for other chaperone systems to survive proteotoxic stress
      conditions, and protects a wide variety of proteins against stress-induced
      unfolding and aggregation. In vitro studies reveal that polyP has protein-like
      chaperone qualities, binds to unfolding proteins with high affinity in an ATP
      independent manner, and supports their productive refolding once nonstress
      conditions are restored. Our results uncover a universally important function for
      polyP and suggest that these long chains of inorganic phosphate may have served
      as one of nature's first chaperones, a role that continues to the present day.

PMID- 24560924
TI  - Oncogenic RET kinase domain mutations perturb the autophosphorylation trajectory
      by enhancing substrate presentation in trans.
AB  - To decipher the molecular basis for RET kinase activation and oncogenic
      deregulation, we defined the temporal sequence of RET autophosphorylation by
      label-free quantitative mass spectrometry. Early autophosphorylation sites map to
      regions flanking the kinase domain core, while sites within the activation loop
      only form at later time points. Comparison with oncogenic RET kinase revealed
      that late autophosphorylation sites become phosphorylated much earlier than wild
      type RET, which is due to a combination of an enhanced enzymatic activity,
      increased ATP affinity, and surprisingly, by providing a better intermolecular
      substrate. Structural analysis of oncogenic M918T and wild-type RET kinase
      domains reveal a cis-inhibitory mechanism involving tethering contacts between
      the glycine-rich loop, activation loop, and alphaC-helix. Tether mutations only
      affected substrate presentation but perturbed the autophosphorylation trajectory
      similar to oncogenic mutations. This study reveals an unappreciated role for
      oncogenic RET kinase mutations in promoting intermolecular autophosphorylation by
      enhancing substrate presentation.

PMID- 24560925
TI  - A splicing-dependent transcriptional checkpoint associated with prespliceosome
      formation.
AB  - There is good evidence for functional interactions between splicing and
      transcription in eukaryotes, but how and why these processes are coupled remain
      unknown. Prp5 protein (Prp5p) is an RNA-stimulated adenosine triphosphatase
      (ATPase) required for prespliceosome formation in yeast. We demonstrate through
      in vivo RNA labeling that, in addition to a splicing defect, the prp5-1 mutation
      causes a defect in the transcription of intron-containing genes. We present
      chromatin immunoprecipitation evidence for a transcriptional elongation defect in
      which RNA polymerase that is phosphorylated at Ser5 of the largest subunit's
      heptad repeat accumulates over introns and that this defect requires Cus2
      protein. A similar accumulation of polymerase was observed when prespliceosome
      formation was blocked by a mutation in U2 snRNA. These results indicate the
      existence of a transcriptional elongation checkpoint that is associated with
      prespliceosome formation during cotranscriptional spliceosome assembly. We
      propose a role for Cus2p as a potential checkpoint factor in transcription.

PMID- 24560926
TI  - Regulation of autophagy by cytosolic acetyl-coenzyme A.
AB  - Acetyl-coenzyme A (AcCoA) is a major integrator of the nutritional status at the
      crossroads of fat, sugar, and protein catabolism. Here we show that nutrient
      starvation causes rapid depletion of AcCoA. AcCoA depletion entailed the
      commensurate reduction in the overall acetylation of cytoplasmic proteins, as
      well as the induction of autophagy, a homeostatic process of self-digestion.
      Multiple distinct manipulations designed to increase or reduce cytosolic AcCoA
      led to the suppression or induction of autophagy, respectively, both in cultured
      human cells and in mice. Moreover, maintenance of high AcCoA levels inhibited
      maladaptive autophagy in a model of cardiac pressure overload. Depletion of AcCoA
      reduced the activity of the acetyltransferase EP300, and EP300 was required for
      the suppression of autophagy by high AcCoA levels. Altogether, our results
      indicate that cytosolic AcCoA functions as a central metabolic regulator of
      autophagy, thus delineating AcCoA-centered pharmacological strategies that allow
      for the therapeutic manipulation of autophagy. 

PMID- 24560927
TI  - MICU1 and MICU2 finely tune the mitochondrial Ca2+ uniporter by exerting opposite
      effects on MCU activity.
AB  - Mitochondrial calcium accumulation was recently shown to depend on a complex
      composed of an inner-membrane channel (MCU and MCUb) and regulatory subunits
      (MICU1, MCUR1, and EMRE). A fundamental property of MCU is low activity at
      resting cytosolic Ca(2+) concentrations, preventing deleterious Ca(2+) cycling
      and organelle overload. Here we demonstrate that these properties are ensured by
      a regulatory heterodimer composed of two proteins with opposite effects, MICU1
      and MICU2, which, both in purified lipid bilayers and in intact cells, stimulate
      and inhibit MCU activity, respectively. Both MICU1 and MICU2 are regulated by
      calcium through their EF-hand domains, thus accounting for the sigmoidal response
      of MCU to [Ca(2+)] in situ and allowing tight physiological control. At low
      [Ca(2+)], the dominant effect of MICU2 largely shuts down MCU activity; at higher
      [Ca(2+)], the stimulatory effect of MICU1 allows the prompt response of
      mitochondria to Ca(2+) signals generated in the cytoplasm.

PMID- 24560928
TI  - Survivin beyond physiology: orchestration of multistep carcinogenesis and
      therapeutic potentials.
AB  - Survivin, a member of the inhibitor of apoptosis protein family, has been
      associated with protection from cell apoptosis and regulation of mitosis.
      Survivin exhibits low to undetectable expression in most finally differentiated
      adult tissues but is abundantly over-expressed in almost all cancers. The
      aberrant high expression of survivin in cancers is associated with advanced
      disease, increased rate of tumor recurrence, abbreviated overall survival and
      resistance to chemo- and radio- therapy. Survivin touches nearly every aspect of
      cancer and is involved in the initiation, maintenance and development of tumor.
      Therefore, its significance in cancer dictates the pursuit for anti-survivin
      cancer therapies. 

PMID- 24560931
TI  - Molecular characterization and expression analysis of a GTP-binding protein
      (MiRab5) in Mangifera indica.
AB  - The Rab family, the largest branch of Ras small GTPases, plays a crucial role in
      the vesicular transport in plants. The members of Rab family act as molecular
      switches that regulate the fusion of vesicles with target membranes through
      conformational changes. However, little is known about the Rab5 gene involved in
      fruit ripening and stress response. In this study, the MiRab5 gene was isolated
      from stress-induced Mangifera indica. The full-length cDNA sequence was 984bp and
      contained an open reading frame of 600bp, which encoded a 200 amino acid protein
      with a molecular weight of 21.83kDa and a theoretical isoelectric point of 6.99.
      The deduced amino acid sequence exhibited high homology with tomato (91%
      similarity) and contains all five characteristic Rab motifs. Real-time
      quantitative RT-PCR analysis demonstrated that MiRab5 was ubiquitously expressed
      in various mango tree tissues at different levels. The expression of MiRab5 was
      up-regulated during later stages of fruit ripening. Moreover, MiRab5 was
      generally up-regulated in response to various abiotic stresses (cold, salinity,
      and PEG treatments). Recombinant MiRab5 protein was successfully expressed and
      purified. SDS-PAGE and western blot analysis indicated that the expressed protein
      was recognized by the anti-6-His antibody. These results provide insights into
      the role of the MiRab5 gene family in fruit ripening and stress responses in the
      mango plant. 

PMID- 24560932
TI  - The relation between hairpin formation by mitochondrial WANCY tRNAs and the
      occurrence of the light strand replication origin in Lepidosauria.
AB  - Mitochondrial light strand DNA replication is initiated at light strand
      replication origins (OLs), short stem-loop hairpins formed by the heavy strand
      DNA. OL-like secondary structures are also formed by heavy strand DNA templating
      for the five tRNAs adjacent to OLs, the WANCY tRNA cluster. We tested whether
      natural OL absence associates with greater capacities for formation of OL-like
      structures by WANCY tRNA genes. Using lepidosaurian taxa (Sphenodon, lizards and
      amphisbaenids), we compared WANCY tRNA capacities to form OL-like structures
      between 248 taxa possessing an OL with 131 taxa without OL (from different
      families). On average, WANCY tRNA genes form more OL-like structures in the
      absence of a regular OL than in its presence. Formation of OL-like structures by
      WANCY tRNAs follows hierarchical patterns that may reduce competition between the
      tRNA's translational function and its secondary OL function: the rarer the tRNA's
      cognate amino acid, the greater the capacity to form OL-like structures. High OL
      forming capacities for neighboring tRNAs are avoided. Because OL absence usually
      occurs in taxa with reduced genomes, increased formation of OL-like structures by
      WANCY tRNAs might result from selection for greater metabolic efficiency. Further
      analyses suggest that OL loss is one of the latest steps in genome reduction, and
      promotes the increase in formation of OL-like structures by WANCY tRNA genes in
      Lepidosauria.

PMID- 24560929
TI  - Understanding the relationship between DNA methylation and histone lysine
      methylation.
AB  - DNA methylation acts as an epigenetic modification in vertebrate DNA. Recently it
      has become clear that the DNA and histone lysine methylation systems are highly
      interrelated and rely mechanistically on each other for normal chromatin function
      in vivo. Here we examine some of the functional links between these systems, with
      a particular focus on several recent discoveries suggesting how lysine
      methylation may help to target DNA methylation during development, and vice
      versa. In addition, the emerging role of non-methylated DNA found in CpG islands
      in defining histone lysine methylation profiles at gene regulatory elements will
      be discussed in the context of gene regulation.

PMID- 24560930
TI  - ADHD, altered dopamine neurotransmission, and disrupted reinforcement processes:
      implications for smoking and nicotine dependence.
AB  - Attention deficit hyperactivity disorder (ADHD) is a common and impairing
      disorder affecting millions of children, adolescents, and adults. Individuals
      with ADHD smoke cigarettes at rates significantly higher than their non-diagnosed
      peers and the disorder also confers risk for a number of related adverse smoking
      outcomes including earlier age of initiation, faster progression to regular use,
      heavier smoking/greater dependence, and more difficulty quitting. Progress in our
      understanding of dopamine neurotransmission and basic behavioral reinforcement
      processes in ADHD may help increase our understanding of the ADHD-smoking
      comorbidity. This review will examine how these areas have been studied and how
      further work may aid in the development of better prevention and treatment for
      smoking in those with ADHD. 

PMID- 24560933
TI  - A single-nucleotide polymorphism in tumor necrosis factor-alpha (-308 G/A) as a
      biomarker in chronic pancreatitis.
AB  - OBJECTIVE: Chronic pancreatitis is a gradual, long-term inflammation of the
      pancreas that results in alteration of its normal structure and function. The
      study aims to investigate the role of -308 (G/A) polymorphism of TNF-alpha gene
      in chronic pancreatitis. MATERIAL AND METHODS: A total of 200 subjects were
      included in this case-control study. A total of 100 in patients admitted in the
      Gastroenterology Unit of Gandhi Hospital and Osmania General Hospital, Hyderabad
      were included in the present study. An equal number of healthy control subjects
      were randomly selected for the study. The genotyping of TNF-alpha gene was
      carried out by tetra-primer ARMS PCR followed by gel electrophoresis. The TNF
      alpha levels were assayed by enzyme-linked immunosorbent assay. RESULTS: A
      significant variation with respect to the genotypic and allelic distribution in
      the disease group when compared to control subjects [OR=2.001 (1.33-3.005),
      p<0.0001**] was observed. Subjects homozygous for the A allele had higher TNF
      alpha levels compared to G allele. CONCLUSION: The present study revealed a
      significant association of the TNF-alpha gene promoter polymorphism with chronic
      pancreatitis. Thus, TNF-alpha genotype can be considered as one of the biological
      markers in the etiology of chronic pancreatitis.

PMID- 24560934
TI  - Extemporaneously prepared controlled release formulations for accelerating the
      early phase development of drug candidates.
AB  - Extemporaneous drug preparations, which are compounded by a pharmacist at a
      clinical site, are commonly used in early clinical studies to evaluate the
      performance of drug candidates. However, the types of formulations compounded
      have been limited to relatively simple preparations such as solutions,
      suspensions and active ingredients filled into capsules. This article describes
      the preparation of advanced formulations, specifically extemporaneously prepared
      matrix tablets and osmotic capsules, which can be used to evaluate the
      feasibility of controlled release for exploratory new drug candidates or new
      formulations of existing drugs with a differentiated medical advantage.
      Extemporaneously prepared dosage forms enable the rapid assessment (i.e. reduced
      cycle time) of new formulation ideas with minimal quantity of the active
      pharmaceutical ingredient needed to demonstrate proof-of-concept. 

PMID- 24560935
TI  - Activity cliffs in drug discovery: Dr Jekyll or Mr Hyde?
AB  - The impact activity cliffs have on drug discovery is double-edged. For instance,
      whereas medicinal chemists can take advantage of regions in chemical space rich
      in activity cliffs, QSAR practitioners need to escape from such regions. The
      influence of activity cliffs in medicinal chemistry applications is extensively
      documented. However, the 'dark side' of activity cliffs (i.e. their detrimental
      effect on the development of predictive machine learning algorithms) has been
      understudied. Similarly, limited amounts of work have been devoted to propose
      potential solutions to the drawbacks of activity cliffs in similarity-based
      approaches. In this review, the duality of activity cliffs in medicinal chemistry
      and computational approaches is addressed, with emphasis on the rationale and
      potential solutions for handling the 'ugly face' of activity cliffs. 

PMID- 24560936
TI  - Transmission paths of Neospora caninum in a dairy herd of crossbred cattle in the
      northeast of Brazil.
AB  - The aim of this study was to determine the transmission paths of Neospora caninum
      in a dairy herd of crossbred cattle. Two hundred and ninety animals were grouped
      according to the year of their birth to verify the distribution of infection
      according to age. The blood of 196 cattle was collected thrice, with an average
      interval of 210 days, to evaluate the existence of horizontal transmission in the
      herd. To evaluate vertical transmission, the blood of 64 calves was collected
      prior to ingestion of colostrum and from their mothers at parturition. Moreover,
      63 family trees were built. The presence of anti-N. caninum antibodies was
      detected using an indirect fluorescent antibody test. The chi-square test
      (chi(2)) with Yates' correction or Fisher's exact test was used to evaluate the
      relation between the serology and age groups and between the serostatus of cows
      and their progeny in different calvings. A higher seropositivity (p=0.035) was
      found in animals born in 2008 compared to those born in 1997-2007. The
      serological status of only 13 animals presented changes, of which six (3.1%)
      became seropositive, indicating a low proportion of horizontal transmission. All
      seropositive cows gave birth to seropositive calves, resulting in 100% vertical
      transmission. Sixty-three family trees were constructed. In 29 (46%) of these
      families, there were animals seropositive for N. caninum. Congenital infection in
      relation to the number of births was estimated from the relation of Mother+ and
      Daughter+, without significant differences (p=0.84) between the number of births
      and the transmission of the parasite from infected cows to their progeny. The low
      proportion of horizontal transmission combined with the high proportion of
      vertical transmission allowed us to conclude that transplacental transmission is
      the principal route of N. caninum infection in the herd. 

PMID- 24560937
TI  - TADG-12 as an early marker in the development of pancreatic ductal adenocarcinoma
      (PDAC): involvement of insulin containing cells.
AB  - TADG-12 is a serine protease that was characterized as expressed in ovarian and
      gastric carcinomas. Pancreatic ductal adenocarcinoma (PDAC) is one of the most
      lethal cancers and its late detection results in poor prognosis. Therefore, we
      decided to examine whether TADG-12 appears early in PDAC development. In normal
      pancreas, pale to moderate immunostaining is present in islets of Langerhans,
      while exocrine tissue and ducts are free from labeling. In contrast, in cancer
      patients, who still preserve the integrity of the exocrine and the endocrine
      tissues, a pronounced immunolabelling of TADG-12 was evident mainly located in
      the insulin containing beta cells. In a more progressive stage of the disease
      TADG-12 was also evident in the deteriorated exocrine tissue. TADG-12 was also
      heavily labeled in islets of Langerhans, which were embedded in the stroma of the
      residual pancreatic tissue. Again, there was a considerable overlap between the
      labeling of insulin and TADG-12 in these islets. Close correlation between
      insulin and TADG-12 was also evident in islets of Langerhans surrounded by
      adipose cells. The TADG-12 labeled was confined to the cytoplasm and the membrane
      of the cells. In the progressive stage of PDAC, the cancerous ducts were clearly
      labeled with TADG-12 with no labeling of insulin. At high magnification the TADG
      12 clearly labeled the cytoplasm and the cell wall membrane of duct cells, while
      the nuclei remained unstained upon incubation with antibodies to TADG-12. The
      present findings may assist in early detection of PDAC as well as targeting of
      TADG-12 in order to attenuate the rapid progression of the disease. 

PMID- 24560938
TI  - A simple and rapid decalcification procedure of skeletal tissues for pathology
      using an ultrasonic cleaner with D-mannitol and formic acid.
AB  - Decalcification procedures are required in order to prepare histopathological
      preparations of hard tissues such as bone and teeth. Decalcification is usually
      performed by immersing the hard tissue in different decalcification fluids with
      various properties. These decalcification fluids typically include inorganic and
      organic acids, a neutral fluid containing a chelating agent, or a mixture of
      solutions. Unfortunately, there is no universal decalcification fluid that
      satisfies all the requirements of pathologists such as rapid decalcification,
      easy handling, and minimal tissue damage. Techniques involving use of microwaves
      (MW) or ultrasonic apparatus (US) have been shown to be useful for shortening the
      time for decalcification procedures. In the present study, we investigated a
      unique decalcification procedure that uses a common commercial ultrasonic cleaner
      and a decalcification fluid (formic acid) containing a free-radical scavenger (D
      mannitol). The time required to complete the procedure is approximately half of
      that required to complete a standard decalcification procedure. In addition,
      tissue morphology and antigenicity is fairly well preserved after
      decalcification. The procedure is quick, easy to perform, and achieves
      decalcification of hard tissue with minimal tissue damage. 

PMID- 24560939
TI  - Effects of neem oil (Azadirachta indica A. Juss) on the replacement of the midgut
      epithelium in the lacewing Ceraeochrysa claveri during larval-pupal
      metamorphosis.
AB  - Larvae of the lacewing Ceraeochrysa claveri were fed on eggs of
      Diatraeasaccharalis treated with neem oil at concentrations of 0.5%, 1% and 2%
      throughout the larval period. Pupae obtained from treated larvae were used in the
      study at five days after the completion of cocoon spinning to investigate the
      effects of neem oil on the replacement of the midgut epithelium during the larval
      pupal transition. We observed that the old larval epithelium was shed into the
      midgut lumen and transformed into the yellow body. Old cells from the yellow body
      were destroyed by apoptosis and autophagy and were not affected by neem oil.
      However, neem oil did affect the new pupal epithelium. Cells from treated pupae
      showed cellular injuries such as a loss of microvilli, cytoplasmic vacuolization,
      an increase of glycogen stores, deformation of the rough endoplasmic reticulum
      and dilation of the perinuclear space. Additionally, the neem oil treatment
      resulted in the release of cytoplasmic protrusions, rupture of the plasma
      membrane and leakage of cellular debris into the midgut lumen, characteristics of
      cell death by necrosis. The results indicate that neem oil ingestion affects the
      replacement of midgut epithelium, causing cytotoxic effects that can alter the
      organism's physiology due to extensive cellular injuries. 

PMID- 24560940
TI  - Non-invasive, epicutaneous immunisation with toxoid in deformable vesicles
      protects mice against tetanus, chiefly owing to a Th2 response.
AB  - A non-invasive, intra/transcutaneous immunisation of mice with a suitable
      combination of tetanus toxoid, ultradeformable vesicle (Transfersome(r)) carrier,
      and monophosphoryl lipid A adjuvant targets immuno-competent cells in a body and
      can protect 100% of the tested mice against an otherwise lethal (50*LD50)
      parenteral tetanus toxin challenge. The late immune response to the
      epicutaneously applied tetanus toxoid in such vesicles consists chiefly of
      circulating IgG1 and IgG2b antibody isotypes, indicative of a specific Th2
      cellular response bias. Immunisations by subcutaneous injections moreover protect
      100% of mice against a similar, otherwise lethal, dose of tetanus toxin. However,
      the immune response to transcutaneous and invasive immunisation differs. The
      latter elicits mainly IgG1 and IgG2b as well as IgG2a antibody isotypes,
      indicative of a mixed Th1/Th2 response. The cytokine response of the
      intra/transcutaneously and subcutaneously immunised mice reflects the difference
      in the organ-specific manner. IFN-gamma concentration is appreciably increased in
      the draining lymph nodes and IL-10 in spleen. Since tetanus is a neutral antigen,
      both the Th1-specific IFN-gamma and the Th-2 specific-IL-10 are observable. 

PMID- 24560941
TI  - Synthesis and in vitro biological evaluation of aminoacridines and artemisinin
      acridine hybrids.
AB  - During this study, 9-aminoacridine and artemisinin-acridine hybrid compounds were
      synthesized and the in vitro for antimalarial activity against both the
      chloroquine sensitive but also gametocytocidal strain (NF54), and chloroquine
      resistant (Dd2) strains of Plasmodium falciparum was determined. In vitro
      cytotoxicity against CHO cells, apoptosis of HepG2 and SH-SY5Y as well as
      anticancer activity against HeLa cell lines were assessed. The hybrids were
      synthesized, using a microwave-assisted radiation method by covalently linking
      artemisinin and acridine pharmacophores by means of a liable, aminoethyl ether
      linker. The synthesized compounds were found active against both the Plasmodium
      strains and displayed superior selective toxicity towards the parasitic cells.
      Hybrid 7, however, containing ethylenediamine linker, proved the most active of
      all of the synthesized compounds. It had seven-fold higher antigametocytocidal
      activity compared to chloroquine and was also found to be seven-fold more potent
      than chloroquine against the Dd2 strain, with highly selective action towards the
      parasitic cells. This hybrid also showed favourable anti-cancer activity against
      the HeLa cells, three- and eight-fold higher than those of chloroquine and
      melphalan, respectively. This hybrid may therefore stand as drug candidate for
      further investigation in the search for new and effective drugs against malaria
      and cervical cancer. 

PMID- 24560942
TI  - [Objective assessment of the functional impact of dry eye severity on the quality
      of vision by double-pass aberrometry].
AB  - PURPOSE: To assess the functional impact of the severity of dry eye on the
      quality of vision by measuring an Objective Scatter Index (OSI) using double pass
      aberrometry. PATIENTS AND METHODS: Twenty-eight patients (56 eyes) with dry eye
      syndromes of varying severity participated in this study. A double-pass
      aberrometer was used to measure the dynamic changes in the OSI for 20 seconds.
      The mean and standard deviations of the OSI and the number of blinks occurring
      during the examination were compared as a function of the clinical severity of
      dry eye disease. RESULTS: The mean OSI increased with the severity of dry eye
      syndrome with a significant difference for stages 3 (P<0.01) and 4 (P<0.001)
      compared to stages 1 and 2, without a significant difference based on age (P>0.8)
      or visual acuity (P>0.2). Standard deviation of the OSI also increased with the
      severity of dry eye disease, with a significant difference for stages 3 (P<0.01)
      and 4 (P<0.0001) compared to stages 1 and 2, with no significant increase in the
      number of blinks (P>0.2). The values of the OSI standard deviation represented
      the dynamic nature of aberrometric changes related to the instability of the tear
      film. CONCLUSION: Quality of vision of patients deteriorated in relation to the
      severity of their dry eye. The analysis of OSI standard deviation appears to be
      an objective way to assess the intensity of subjective visual disturbances
      reported by patients with dry eye syndrome. It also provides a new tool to assess
      the severity of damage to the ocular surface.

PMID- 24560943
TI  - [Choroidal thickness assessment with SD-OCT in high myopia with dome-shaped
      macula].
AB  - PURPOSE: To measure macular choroidal thickness (CT) using spectral-domain
      optical coherence tomography (SD-OCT) in highly myopic eyes with dome-shaped
      macula (DSM), and to investigate whether the choroid is thicker in these eyes
      compared to highly myopic eyes without MB. PATIENTS AND METHODS: A cross
      sectional study of 200 eyes was performed between January 2010 and June 2012.
      Twenty-four highly myopic eyes (12%) had a dome-shaped macula. All patients
      underwent a complete ophthalmological examination, SD-OCT (TOPCON 2000), and B
      scan ultrasonography. OCT scans were analyzed in 7 sections, and subfoveal CT was
      measured manually between the Bruch's membrane and the internal aspect of the
      sclera. The 20 eyes with isolated dome-shaped macular were paired by age and
      axial length (AL) with 20 eyes without macular involvement. RESULTS: In the
      subgroup with isolated MB, the mean subfoveal CT was 101.86 MUm (+/- 21.35 MUm).
      A statistically significant negative correlation was found between CT and AL (r=
      0.623, P=0.0001). The regression equation demonstrated a decrease of 8.3 MUm per
      mm of AL. In the subgroup without MB, matched with the subgroup with MB by age
      (P=0.591), and AL (P=0.815), the mean subfoveal CT was 89.54 MUm (+/- 20.12 MUm).
      The comparison between the two subgroups found a statistically significant
      difference in subfoveal CT (P<10-4). CONCLUSIONS: In our study, choroidal
      thickness is increased in highly myopic eyes with dome-shaped macula compared to
      highly myopic eyes without dome-shaped macula. These findings suggest that
      abnormalities of the choroid may play a role in the pathogenesis of dome-shaped
      macula.

PMID- 24560944
TI  - Thorotrast and in vivo thorium dioxide: numerical simulation of 30 years of alpha
      radiation absorption by the tissues near a large compact source.
AB  - BACKGROUND: The epidemiology of the slightly radioactive contrast agent named
      Thorotrast presents a very long latency period between the injection and the
      development of the related pathologies. It is an example of the more general
      problem posed by a radioactive internal contaminant whose effects are not
      noteworthy in the short term but become dramatic in the long period. A point that
      is still to be explored is fluctuations (in space and time) in the localized
      absorption of radiation by the tissues. METHODS: A Monte Carlo simulation code
      has been developed to study over a 30-year period the daily absorption of alpha
      radiation by MUm-sized portions of tissue placed at a distance of 0-100 MUm from
      a model source, that approximates a compact thorium dioxide source in liver or
      spleen whose size is ?20 MUm. The biological depletion of the daughter nuclei of
      the thorium series is taken into account. The initial condition assumes
      chemically purified natural thorium. RESULTS: Most of the absorbed dose is
      concentrated in a 25-MUm thick layer of tissue, adjacent to the source boundary.
      Fluctuations where a target region with a volume of 1 MUm(3) is hit by 3-5 alpha
      particles in a day or in a shorter period of time are relevant in a 1-10 MUm
      thick layer of tissue adjacent to the source boundary, where their frequency is
      larger than the Poisson-law prediction.

PMID- 24560945
TI  - A simple approach for morphology tailoring of alginate particles by manipulation
      ionic nature of polyurethanes.
AB  - A number of different ionic aqueous polyurethane dispersions (PUDs) were
      synthesized based on NCO-terminated prepolymers. Two different anionic and
      cationic polyurethane samples were synthesized using dimethylol propionic acid
      and N-methyldiethanolamine emulsifiers, respectively. Then, proper amounts of
      PUDs and sodium alginate were mixed to obtain a number of aqueous polyurethane
      dispersions-sodium alginate (PUD/SA) elastomers. The chemical structure, thermal,
      morphological, thermo-mechanical and mechanical properties, and hydrophilicity
      content of the prepared samples were studied by FTIR, EDX, DSC, TGA, SEM, DMTA,
      tensile testing and contact angle techniques. The cationic polyurethanes and
      their blends with sodium alginate showed excellent miscibility and highly
      stretchable properties, while the samples containing anionic polyurethanes and
      alginate illustrated a poor compatibility and no significant miscibility. The
      morphology of alginate particles shifted from nanoparticles to microparticles by
      changing the nature of PUDs from cationic to anionic types. The final cationic
      elastomers not only showed better mechanical properties but also were formulated
      easier than anionic samples.

PMID- 24560946
TI  - MicroRNAs expression and their regulatory networks during mesenchymal stem cells
      differentiation toward osteoblasts.
AB  - MicroRNAs (miRNAs) are small endogenous noncoding RNAs which regulate mRNAs post
      transcriptionally. In this study, a selective number of miRNAs was investigated
      for their expression and intracellular regulatory networks involved in
      differentiation of human mesenchymal stem cells (hMSCs) toward osteoblasts. The
      expression of miR-424, miR-106a, miR-148a, let-7i and miR-99a miRNAs was found to
      be specific in hMSCs; whereas expression of miR-15b, miR-24, miR-130b, miR-30c,
      and miR-130a miRNAs was found to be specific in differentiated osteoblasts. A
      bioinformatics approach identified that the MAPK pathway was mostly targeted by
      hMSCs specific miRNAs; whereas JAK-STAT, p53, Focal adhesion, gap junction,
      ubiquitin mediated proteolysis pathways were targeted by osteblastic specific
      miRNAs. Altering expression of osteoblast specific miRNA (miR-15b) promoted
      adipogenesis and myogenesis lineages. Thus, we suggest that miRNAs' regulatory
      networks and their target genes might provide an insight of their role during
      differentiation of hMSCs toward osteoblasts, and alteration in the expression of
      miRNAs would be a valuable approach for controlling osteoblast differentiation.

PMID- 24560947
TI  - Sorption studies on Cr (VI) removal from aqueous solution using cellulose grafted
      with acrylonitrile monomer.
AB  - Graft copolymerization of acrylonitrile on to cellulosic material derived from
      sisal fiber can be initiated effectively with ceric ammonium nitrate. The
      grafting conditions were optimized by changing the concentration of initiator and
      monomer. The change in crystallinity of the grafted polymeric samples was
      concluded from the XRD patterns. The prepared cellulose grafted acrylonitrile
      copolymer was used as an adsorbent to remove Cr (VI) ions from aqueous solutions.
      The efficiency of the adsorbent was identified from the variation in the
      percentage of adsorption with contact time, adsorbent dose and pH. From the
      observed results it was evident that the adsorption of metal ions increases with
      the increase in contact time and metal ion concentration. An optimum pH was found
      to be 5.0 for the removal of Cr (VI) from the aqueous solution. The results of
      the Langmuir, Freundlich, and pseudo first- and second-order studies revealed
      that the adsorption was found to fit well with Freundlich isotherm and follows
      pseudo second-order kinetics. From the above results, it was concluded that the
      cellulose-g-acrylonitrile copolymer was found to be an efficient adsorbent for
      the removal of Cr (VI) from aqueous waste generated from industries.

PMID- 24560948
TI  - Preparation of magnetic ionic liquid/chitosan/graphene oxide composite and
      application for water treatment.
AB  - Magnetic chitosan and graphene oxide-ionic liquid (MCGO-IL) composites as
      biodegradable biosorbents were synthesized by impregnating MCGO with ionic
      liquid. The characteristic results of FTIR, SEM, and XRD showed that MCGO-IL were
      successfully prepared with large surface area and good magnetic responsiveness.
      They were used for the removal of Cr(VI) from simulated wastewater with a fast
      solid-liquid separation in the presence of external magnetic field. The influence
      of various analytical parameters on the adsorption of Cr(VI) such as pH, contact
      time, and initial ion concentration were studied in detail. The adsorption
      followed a pseudo-second-order kinetics. The equilibrium adsorption was well
      described by the Langmuir isotherm mode and the maximum adsorption capacity was
      145.35 mg/g. The stronger intermolecular hydrogen bond between MCGO-IL and Cr(VI)
      and the hydroxyl and amine groups were believed to be the metal ion binding
      sites. Moreover, the MCGO-IL could be repeatedly used by simple treatment without
      obvious structure and performance degradation. The obtained results indicated
      that the impregnation of the room temperature IL significantly enhances the
      removal efficiency of Cr(VI). The MCGO-IL may be suitable materials in heavy
      metal ion pollution cleanup if they are synthesized in large scale and at low
      price in near future.

PMID- 24560949
TI  - Intercalation of antitumor drug doxorubicin and its analogue by DNA duplex:
      structural features and biological implications.
AB  - The intercalation of antitumor drug doxorubicin (DOX) and its analogue N
      (trifluoroacetyl) doxorubicin (FDOX) with DNA duplex was investigated, using
      FTIR, CD, fluorescence spectroscopic methods and molecular modeling. Both DOX and
      FDOX were intercalated into DNA duplex with the free binding energy of -4.99 kcal
      for DOX-DNA and -4.92 kcal for FDOX-DNA adducts and the presence of H-bonding
      network between doxorubicin NH2 group and cytosine-19. Spectroscopic results
      showed FDOX forms more stable complexes than DOX with KDOX-DNA=2.5(+/- 0.5)*
      10(4)M(-1) and KFDOX-DNA=3.4(+/- 0.7)* 10(4)M(-1). The number of drug molecules
      bound per DNA (n) was 1.2 for DOX and 0.6 for FDOX. Major alterations of DNA
      structure were observed by DOX intercalation with a partial B to A-DNA
      transition, while no DNA conformational changes occurred upon FDOX interaction.
      This study further confirms the importance of unmodified daunosamine amino group
      for optimal interactions with DNA. The results of in vitro MTT assay carried out
      on SKC01 colon carcinoma corroborate the observed DNA interactions. Such DNA
      structural changes can be related to doxorubicin antitumor activity, which
      prevents DNA duplication.

PMID- 24560950
TI  - DNA binding and nuclease activity of an oxovanadium valinato-Schiff base complex.
AB  - A new oxovanadium complex [VO(sal-l-val)(phen)] (sal-l-val=Schiff base derived
      from salicylaldehyde and l-valine; phen=1,10-phenanthroline) has been designed
      and synthesized with the aim of developing potential DNA nuclease. The
      interaction of DNA with this structurally characterized oxovanadium complex has
      been studied by various physicochemical tools like UV-vis, fluorescence,
      viscosity and circular dichroism (CD). The intrinsic binding constant of the
      complex with DNA is determined by electronic absorption studies and calculated to
      be (4.74 +/- 0.02)* 10(5)M(-1). The spectroscopic studies and the viscosity
      measurements indicate that the complex binds calf thymus DNA (CT-DNA) by
      intercalative mode. The ability of the complex to induce DNA cleavage was studied
      by gel electrophoresis techniques. The complex has been found to promote cleavage
      of pUC19 plasmid DNA from the super coiled (SC) form I to nicked coiled (NC)
      relaxed form II with good efficiency.

PMID- 24560951
TI  - A novel impedimetric disposable immunosensor for rapid detection of a potential
      cancer biomarker.
AB  - A specific and sensitive biosensor was developed successfully for quantitative
      detection of human epidermal growth factor receptor by electrochemical impedance
      spectroscopy. Anti-human epidermal growth factor receptor antibody was covalently
      immobilized onto a screen-printed carbon electrode modified with a carbon
      nanotube. Immobilization steps were characterized by cyclic voltammetry (CV),
      electrochemical impedance spectroscopy (EIS), and scanning electron microscopy
      (SEM). After human epidermal growth factor receptor ligates with anti-human
      epidermal growth factor receptor immobilized onto an electrode surface, charge
      transfer resistance changes considerably. This electrochemical response was
      correlated with human epidermal growth factor receptor concentration. Under
      optimal conditions, the proposed biosensor could detect human epidermal growth
      factor receptor 2 fg/mL with a linear range from 2 to 14 fg/mL, showing high
      sensitivity. Kramers-Kronig Transform was performed on the experimental impedance
      data. Meanwhile, in a biosensor system, the Single Frequency Impedance technique
      was first used for characterization of interaction between human epidermal growth
      factor receptor and anti-human epidermal growth factor receptor. Eventually, the
      proposed biosensor was applied to artificial serum samples spiked with human
      epidermal growth factor receptor.

PMID- 24560952
TI  - Evaluation of saccharin intake and expression of fructose-conditioned flavor
      preferences following opioid receptor antagonism in the medial prefrontal cortex,
      amygdala or lateral hypothalamus in rats.
AB  - In prior studies, systemic opioid receptor antagonism with naltrexone (NTX)
      failed to block flavor preference conditioning by the sweet taste or post-oral
      actions of sugar despite reducing overall flavored saccharin intake. Further, NTX
      microinjections into the nucleus accumbens (NAc) shell or core failed to alter
      the expression of preferences conditioned by the sweet taste or post-oral actions
      of sugars. In contrast, fructose-conditioned flavor preferences (CFP) were
      reduced or eliminated by systemic or intracerebral administration of dopamine
      (DA) D1 or D2 antagonists in the NAc, medial prefrontal cortex (mPFC), amygdala
      (AMY) or lateral hypothalamus (LH). The present study examined whether NTX
      microinjections into the mPFC, AMY or LH would alter expression of fructose-CFP
      and total flavored saccharin intake. Food-restricted rats with bilateral cannulae
      aimed at the mPFC, AMY or LH were trained to drink a fructose (8%)+saccharin
      (0.2%) solution mixed with one flavor (CS+, e.g., cherry) and a 0.2% saccharin
      solution mixed with another flavor (CS-, e.g., grape) during 10 one-bottle
      sessions. Two-bottle tests with the cherry and grape flavors in 0.2% saccharin
      solutions occurred 10min following total bilateral NTX doses of 0, 1, 25 and
      50MUg administered into the mPFC, AMY or LH. Rats preferred the CS+ over CS-
      flavor following vehicle and all NTX doses administered into either the mPFC or
      LH. CS+ intake was significantly greater than CS- intake following vehicle and
      the low NTX dose in the AMY; however, at the 25 and 50MUg AMY NTX doses, CS+
      intakes did not significantly exceed CS- intakes. Total flavored saccharin intake
      was significantly reduced by all three LH NTX doses (20-35%), by the 25 (14%) and
      50 (22%)MUg AMY NTX doses, but not by mPFC NTX. Thus, opioid antagonism in the
      AMY, but not the mPFC or LH attenuated, but did not block the expression of
      fructose-CFP, and LH and AMY, but not mPFC, NTX significantly reduced total
      saccharin intake. Therefore, whereas opioid antagonism in the LH and AMY reduces
      sweet intake, they appear less effective in altering fructose-CFP. 

PMID- 24560953
TI  - Factor V and VIII combined deficiency: clinical perioperative management for
      tonsillectomy in a child.
AB  - Combined factors V (FV) and VIII (FVIII) deficiency is a rarely seen hereditary
      coagulation disease. Experience of its management in surgery with a high-risk of
      bleeding is rare. The interest of this case report is to propose a strategy of
      perioperative management for such a deficit, but also to recall that a careful
      preoperative anesthetic evaluation with questioning and physical examination
      permits to detect unsuspected coagulation disorders and to schedule the
      preventive treatment. The protocol for the perioperative period consisted of the
      administration of desmopressin and fresh frozen plasma one hour before surgery.
      The administration of desmopressin was continued for 48hours. Fresh frozen plasma
      and tranexamic acid were administered during the first 9 postoperative days. A
      local bleeding occurred at 8 days (scab coming off) and required systematically a
      surgical hemostasis and an intensification of the therapeutic protocol.
      Recombinant plasmatic factor VIII was administered for 7 days together with a
      daily perfusion of fresh frozen plasma for a total treatment period of 14 days. 

PMID- 24560954
TI  - The role of prostatic inflammation biomarkers in the diagnosis of prostate
      diseases.
AB  - Benign prostatic hyperplasia (BPH) and prostate cancer (PCa) are chronic
      conditions, which are hormone-dependent and epidemiologically associated with
      prostate inflammation. As a large number of studies have demonstrated, the
      stimulation of T-cells at the level of prostatic chronic inflammatory infiltrates
      is followed by stromal and epithelial cell proliferation. The aim of this review
      is to present the actual level of knowledge in the field of prostatic immune
      response and chronic inflammation, and to analyze the relationships between
      chronic inflammation and BPH/PCa. The most studied prostatic inflammation
      biomarkers detected in biological fluids are also presented, together with their
      potential roles in the diagnosis and prognosis of prostatic disease. 

PMID- 24560955
TI  - Diagnostic accuracy of presepsin (soluble CD14 subtype) for prediction of
      bacteremia in patients with systemic inflammatory response syndrome in the
      Emergency Department.
AB  - BACKGROUND: Bacteremia is indicative of severe bacterial infection with
      significant mortality. Its early diagnosis is extremely important for
      implementation of antimicrobial therapy but a diagnostic challenge. Although
      blood culture is the "gold standard" for diagnosis of bacteremia this method has
      limited usefulness for the early detection of blood-stream infection. In this
      study we assessed the presepsin as predictor of bacteremia in patients with
      systemic inflammatory response syndrome (SIRS) on admission to the Emergency
      Department and compare it with current available infection biomarkers. METHODS: A
      total of 226 patients admitted to the Emergency Department with SIRS were
      included. In 37 patients blood culture had a positive result (bacteremic SIRS
      group) and 189 had a negative blood culture result (non-bacteremic SIRS group).
      Simultaneously with blood culture, presepsin, procalcitonin (PCT) and C-reactive
      protein (CRP) were measured. Receiver operating characteristic (ROC) curve
      analysis was performed for each biomarker as predictor of bacteremia. RESULTS:
      Presepsin values were significantly higher in bacteremic SIRS group when compared
      with non-bacteremic SIRS group. ROC curve analysis and area under curve (AUC)
      revealed a value of 0.750 for presepsin in differentiating SIRS patients with
      bacteremia from those without, similar than that for PCT (0.787) and higher than
      that for CRP (0.602). The best cut-off value for presepsin was 729pg/mL, which
      was associated with a negative predictive value of 94.4%. CONCLUSION: Presepsin
      may contribute to rule out the diagnosis of bacteremia in SIRS patients admitted
      to the Emergency Department.

PMID- 24560956
TI  - On the transition of genetic differentiation from isolation to panmixia: what we
      can learn from GST and D.
AB  - Population genetic differentiation characterizes the repartition of alleles among
      populations. It is commonly thought that genetic differentiation measures, such
      as GST and D, should be near zero when allele frequencies are close to their
      expected value in panmictic populations, and close to one when they are close to
      their expected value in isolated populations. To analyse those properties, we
      first derive analytically a reference function f of known parameters that
      describes how important features of genetic differentiation (e.g. gene diversity,
      proportion of private alleles, frequency of the most common allele) are close to
      their expected panmictic and isolation value. We find that the behaviour of
      function f differs according to three distinct mutation regimes defined by the
      scaled mutation rate and the number of populations. Then, we compare GST and D to
      f, and demonstrate that their signal of differentiation strongly depends on the
      mutation regime. In particular, we show that D captures well the variations of
      genetic diversity when mutation is weak, otherwise it overestimates it when
      panmixia is not met. GST detects population differentiation when mutation is
      intermediate but has a low sensitivity to the variations of genetic diversity
      when mutation is weak. When mutation is strong the domain of sensitivity of both
      measures are altered. Finally, we also point out the importance of the number of
      populations on genetic differentiation measures, and provide recommendations for
      the use of GST and D. 

PMID- 24560957
TI  - A 10-year experience with major burns from a non-burn intensive care unit.
AB  - OBJECTIVE: The aim of this study was to review clinical data and outcomes of
      patients with burns in a Mexican non-burn intensive care unit (ICU). METHODS: We
      did a retrospective analysis of our single-centre database of burn patients
      admitted to the ICU in the Hospital Civil Fray Antonio Alcalde (University
      Hospital). The sample was divided for analysis into two groups according to the
      outcome 'death' or 'discharge' from ICU. RESULTS: Overall mortality was 58.2%,
      without a decreasing trend in mortality rates through the years. We identified
      the presence of third-degree burns (odds ratio (OR) 1.5, p=0.003), and >49% total
      burned surface area (TBSA; OR 3.3, p<=0.001) was associated with mortality. Mean
      age was higher in deceased patients (38.2 years vs. 31.3 years, p=0.003) as was
      the TBSA (62.8% vs. 36.4%, p<=0.001). At multivariate analysis, inhalation injury
      was not associated with increased mortality, but it was with more mechanical
      ventilation days. Early surgical debridement/cleansing was performed in most
      patients; however, the mean of the procedures was 1.7 per patient in both groups.
      CONCLUSION: We identified significant factors associated with mortality. These
      variables and prognosis from non-burn ICUs differ broadly compared with burn
      intensive care units (BICUs); thus, more structured, multidisciplinary and
      specialised treatment strategies are still needed.

PMID- 24560958
TI  - A baby with symmetrical hand injuries and rhabdomyolysis following nonfatal
      electrocution by an unusual mechanism.
AB  - Childhood electrical injuries are rare in the city of Hong Kong. We report the
      case of a 21-month boy with severe electrical injuries of both hands and explored
      underlying mechanism for the incident. Meticulous orthopedic repair and
      reconstruction ensures satisfactory cosmetic and functional outcomes. Our case
      concurs with the literature that young children may be predisposed to this mode
      of incident with their curious exploring hands. Despite regulations on electrical
      home safety standards, extension power boards can still pose a dangerous risk for
      severe morbidity in the household with young children. Prevention strategies
      often involve commonsense approach in home safety measures such as (1) use proper
      fuses in electrical boxes, (2) do not overload outlets, (3) use insulated and
      grounded electrical cords, (4) keep electrical cords away from a child's reach,
      and (5) cover electrical outlets so children will not stick items in the outlet. 

PMID- 24560959
TI  - Response to letter to the editor: 'sleep quality implicates in life quality: an
      analysis about children who suffered burns.'.

PMID- 24560961
TI  - Propranolol impairs the closure of pressure ulcers in mice.
AB  - AIMS: beta-Adrenoceptors modulate acute wound healing; however, few studies have
      shown the effects of beta-adrenoceptor blockade on chronic wounds. Therefore,
      this study investigated the effect of beta1-/beta2-adrenoceptor blockade in wound
      healing of pressure ulcers. MAIN METHODS: Male mice were daily treated with
      propranolol (beta1-/beta2-adrenoceptor antagonist) until euthanasia. One day
      after the beginning of treatment, two cycles of ischemia-reperfusion by external
      application of two magnetic plates were performed in skin to induce pressure
      ulcer formation. KEY FINDINGS: Propranolol administration reduced keratinocyte
      migration, transforming growth factor-beta protein expression, re
      epithelialization, and necrotic tissue loss. Neutrophil number and neutrophil
      elastase protein expression were increased in propranolol-treated group when
      compared with control group. Propranolol administration delayed macrophage
      mobilization and metalloproteinase-12 protein expression and reduced monocyte
      chemoattractant protein-1 protein expression. Myofibroblastic differentiation,
      angiogenesis, and wound closure were delayed in the propranolol-treated animals.
      Propranolol administration increased neo-epidermis thickness, reduced collagen
      deposition, and enhanced tenascin-C expression resulting in the formation of an
      immature and disorganized collagenous scar. SIGNIFICANCE: beta1-/beta2
      Adrenoceptor blockade delays wound healing of ischemia-reperfusion skin injury
      through the impairment of the re-epithelialization and necrotic tissue loss which
      compromise wound inflammation, dermal reconstruction, and scar formation.

PMID- 24560962
TI  - Pain assessment and management in the NICU: analysis of an educational
      intervention for health professionals.
AB  - OBJECTIVE: to study the perception of a Neonatal Intensive Care team on pain
      assessment and management before and after an educational intervention created
      and implemented in the unit. METHODS: intervention study developed as action
      research, in three phases. In Phase 1, a quantitative study was performed to
      identify how professionals perceive pain management in the unit. In Phase 2, an
      educational intervention was carried out, using the Operational Group (OG), which
      defined strategies to be adopted to seek improvements in pain assessment and
      management. In Phase 3, the initial questionnaire was reapplied to assess
      professionals' perceptions about the subject after the intervention. All
      professionals directly working in newborn care were included. RESULTS: the
      perception of professionals about pain management and assessment in the unit
      showed a statistically significant difference between the two phases of research,
      highlighting the increase in frequency of reference for evaluation and use of
      some method of pain relief procedures for most analyzed procedures. Participation
      in training (one of the strategies defined by the operational group) was reported
      by 86.4% of the professionals. They reported the use of scales for pain
      assessment, established by the protocol adopted in the service after the
      intervention, with a frequency of 94.4%. Changes in pain assessment and
      management were perceived by 79.6% of the participants. CONCLUSION: the
      professionals involved in the educational intervention observed changes in pain
      management in the unit and related them to the strategies defined and implemented
      by the OG.

PMID- 24560960
TI  - Regulation of MMP/TIMP by HUVEC transplantation attenuates ventricular remodeling
      in response to myocardial infarction.
AB  - AIMS: We elucidated the therapeutic potential of human umbilical vein endothelial
      cells (HUVECs) for ameliorating progressive heart failure in a myocardial
      infarction (MI) rat model. MAIN METHODS: MI was induced by ligation of left
      anterior descending artery, and HUVEC was transplanted 1week after MI. Cardiac
      function was evaluated by echocardiography, and histological analyses were
      performed. KEY FINDINGS: Phosphate-buffered saline (MI-V, n=5) or HUVEC (MI-HV,
      n=5) were injected into the border zone and infarcted area 7days after ligation
      of the left coronary artery in rats. The MI-HV group showed attenuation of left
      ventricular (LV) remodeling compared with the MI-V group. In the infarcted
      myocardium, a few of injected HUVEC was retained up to 28days. The ratios of
      matrix metalloproteinase (MMP)-2 or MMP-9 to tissue inhibitor of
      metalloproteinase (TIMP)-1 or TIMP-3 were decreased in the MI-HV group compared
      with the MI-V group. In vivo zymography analysis showed that HUVEC
      transplantation decreased the activities of MMP-2 and MMP-9. In
      immunohistochemistry, decreased MMP-2 and increased TIMP-1 and TIMP-3 expression
      were observed at 48h after HUVEC transplantation. These effects on MMP/TIMP
      balance were inhibited by L-NAME administration (an eNOS inhibitor, 10mg/kg). NOS
      inhibition decreased the protein expressions of TIMP-1 and TIMP-3 but did not
      change the protein expressions of MMP-2 and MMP-9. SIGNIFICANCE: Our data suggest
      that altered balance between MMP and TIMP by HUVEC transplantation contributed to
      attenuation of ventricular remodeling after MI via eNOS.

PMID- 24560963
TI  - Circulating Trypanosoma cruzi populations differ from those found in the tissues
      of the same host during acute experimental infection.
AB  - We evaluated the presence and distribution of two Trypanosoma cruzi natural
      isolates in blood, heart, skeletal muscle, liver, and spleen tissues in the acute
      phase of the experimental infection (35 days postinfection) in order to determine
      if the populations present in blood were different to those found in the tissues
      of the same host. Thirty mice were infected with 50 forms of each isolate or with
      a combination of them. Presence and molecular characterization of the parasites
      in the host tissues were determined by specific PCR. Cardiac and skeletal muscle
      alterations were analyzed by histological studies. T. cruzi variability in the
      host tissues was analyzed through RFLP studies. Both isolates used consisted of a
      mixture of two T. cruzi lineages. Specific PCRs were positive for most of the
      samples from the 3 groups analyzed. Cardiac and skeletal muscle sections from the
      groups infected with one isolate presented mild to moderate inflammatory
      infiltrates; the group infected with both isolates showed severe inflammatory
      infiltrates and the presence of amastigote nests in both tissues. Different
      parasite populations were found in circulation and in the tissues from the same
      host. These results are important for patients with high probability of mixed
      infections in endemic areas and contribute to the knowledge of parasite/host
      interactions. 

PMID- 24560964
TI  - Pentamidine exerts in vitro and in vivo anti Trypanosoma cruzi activity and
      inhibits the polyamine transport in Trypanosoma cruzi.
AB  - Pentamidine is an antiprotozoal and fungicide drug used in the treatment of
      leishmaniasis and African trypanosomiasis. Despite its extensive use as
      antiparasitic drug, little evidence exists about the effect of pentamidine in
      Trypanosoma cruzi, the etiological agent of Chagas' disease. Recent studies have
      shown that pentamidine blocks a polyamine transporter present in Leishmania
      major; consequently, its might also block these transporters in T. cruzi.
      Considering that T. cruzi lacks the ability to synthesize putrescine de novo, the
      inhibition of polyamine transport can bring a new therapeutic target against the
      parasite. In this work, we show that pentamidine decreases, not only the
      viability of T. cruzi trypomastigotes, but also the parasite burden of infected
      cells. In T. cruzi-infected mice pentamidine decreases the inflammation and
      parasite burden in hearts from infected mice. The treatment also decreases
      parasitemia, resulting in an increased survival rate. In addition, pentamidine
      strongly inhibits the putrescine and spermidine transport in T. cruzi
      epimastigotes and amastigotes. Thus, this study points to reevaluate the utility
      of pentamidine and introduce evidence of a potential new action mechanism. In the
      quest of new therapeutic strategies against Chagas disease, the extensive use of
      pentamidine in human has led to a well-known clinical profile, which could be an
      advantage over newly synthesized molecules that require more comprehensive trials
      prior to their clinical use. 

PMID- 24560965
TI  - New description of Toxoplasma gondii genotypes from French Polynesia.
AB  - We report here the first isolation and genotyping of two human Toxoplasma gondii
      strains from French Polynesia. The parasites had new and atypical genotypes, and
      were responsible for asymptomatic congenital toxoplasmosis. Both genotypes were
      divergent from the common strains isolated in Europe, North America, South
      America, Africa and China. 

PMID- 24560966
TI  - Rheological characterization and injection forces of concentrated protein
      formulations: an alternative predictive model for non-Newtonian solutions.
AB  - Development of injection devices for subcutaneous drug administration requires a
      detailed understanding of user capability and forces occurring during the drug
      administration process. Injection forces of concentrated protein therapeutics are
      influenced by syringe properties (e.g., needle diameter) and injection speed, and
      are driven by solution properties such as rheology. In the present study, it is
      demonstrated that concentrated protein therapeutics may show significantly
      reduced injection forces because of shear-thinning (non-Newtonian) behavior. A
      mathematical model was thus established to predict/correlate injection forces of
      Newtonian and non-Newtonian solutions with viscosity data from plate/cone
      rheometry. The model was verified experimentally by glide-force measurements of
      reference and surrogate solutions. Application of the suggested model was
      demonstrated for injection force measurements of concentrated protein solutions
      to determine viscosity data at high shear rates (3 * 10(4)-1.6 * 10(5)s(-1)). By
      combining these data with viscosity data obtained by different viscosity methods
      (plate/cone and capillary rheometry), a viscosity-shear rate profile of the
      protein solution between 10(2) and 1.6 * 10(5)s(-1) was obtained, which was
      mathematically described by the Carreau model. Characterization of rheological
      properties allows to accurately predict injection forces for different syringe
      needle combinations as well as injection rates, thus supporting the development
      of injection devices for combination products.

PMID- 24560967
TI  - Haloperidol-loaded intranasally administered lectin functionalized poly(ethylene
      glycol)-block-poly(D,L)-lactic-co-glycolic acid (PEG-PLGA) nanoparticles for the
      treatment of schizophrenia.
AB  - Lectin-functionalized, polyethylene glycol-block-poly-(D,L)-lactic-co-glycolic
      acid nanoparticles loaded with haloperidol were prepared with narrow size
      distributions and sizes <135nm. The nanoparticles exhibited high Solanum
      tuberosum lectin (STL) conjugation efficiencies, encapsulation efficiencies, and
      drug loading capacities. The in vitro release of haloperidol was 6-8% of the
      loaded amount in endo-lysosomal conditions over 96h, demonstrating minimal drug
      leakage and the potential for the efficient drug transport to the targeted brain
      tissue. The haloperidol released upon erosion was successful in displacing [(3)H]
      N-propylnorapomorphine and binding to bovine striatal dopamine D2 receptors. Both
      haloperidol-loaded nanoparticle formulations were found to be highly effective at
      inducing catalepsy. Intranasal administration of STL-functionalized nanoparticles
      increased the brain tissue haloperidol concentrations by 1.5-3-fold compared to
      non-STL-functionalized particles and other routes of administration. This
      formulation demonstrates promise in the reduction of the drug dose necessary to
      produce a therapeutic effect with antipsychotic drugs for the treatment of
      schizophrenia.

PMID- 24560968
TI  - Riboflavin (vitamin B-2) reduces hepatocellular injury following liver ischaemia
      and reperfusion in mice.
AB  - Riboflavin has been shown to exhibit anti-inflammatory and antioxidant properties
      in the settings of experimental sepsis and ischaemia/reperfusion (I/R) injury. We
      investigated the effect of riboflavin on normothermic liver I/R injury. Mice were
      submitted to 60 min of ischaemia plus saline or riboflavin treatment (30
      MUmoles/kg BW) followed by 6 h of reperfusion. Hepatocellular injury was
      evaluated by aminotransferase levels, reduced glutathione (GSH) content and the
      histological damage score. Hepatic neutrophil accumulation was assessed using the
      naphthol method and by measuring myeloperoxidase activity. Hepatic
      oxidative/nitrosative stress was estimated by immunohistochemistry. Liver
      endothelial and inducible nitric oxide synthase (eNOS/iNOS) and nitric oxide (NO)
      amounts were assessed by immunoblotting and a chemiluminescence assay. Riboflavin
      significantly reduced serum and histological parameters of hepatocellular damage,
      neutrophil infiltration and oxidative/nitrosative stress. Furthermore, riboflavin
      infusion partially recovered hepatic GSH reserves and decreased the liver
      contents of eNOS/iNOS and NO. These data indicate that riboflavin exerts
      antioxidant and anti-inflammatory effects in the ischaemic liver, protecting
      hepatocytes against I/R injury. The mechanism of these effects appears to be
      related to the intrinsic antioxidant potential of riboflavin/dihydroriboflavin
      and to reduced hepatic expression of eNOS/iNOS and reduced NO levels, culminating
      in attenuation of oxidative/nitrosative stress and the acute inflammatory
      response.

PMID- 24560969
TI  - Baicalein inhibits lipid accumulation by regulating early adipogenesis and m-TOR
      signaling.
AB  - Baicalein is a type of flavonoid that originates from Scutellaria baicalensis. In
      this study, we examined how baicalein inhibits lipid accumulation during
      adipogenesis in 3T3-L1 cells. Our data show that baicalein inhibited lipid
      accumulation during adipogenesis in a dose-dependent manner. Baicalein inhibition
      was limited to the early adipogenic stage. Cell cycle analysis showed that
      baicalein induced cell cycle arrest in the G0/G1 phase through cyclin
      downregulation. In addition, baicalein suppressed the mRNA expression of early
      adipogenic factors leading to downregulation of late adipogenic factors at mRNA
      and protein levels. Inhibition of adipogenic factors by baicalein was correlated
      with downregulation of lipid synthetic enzymes. Additionally, baicalein
      negatively regulated the m-TOR signaling pathway involved in lipid accumulation
      during adipogenesis, thus inhibiting phosphorylation of m-TOR and p70S6K. In a
      zebrafish study, baicalein significantly reduced lipid accumulation in Nile Red
      staining. Consistent with a report using cell lines, mRNA expression of
      adipogenic factors was decreased in a dose-dependent manner by baicalein. This
      result reflects a reduction in total triglyceride levels based on a triglyceride
      assay. Our data suggest that baicalein inhibits lipid accumulation by controlling
      the cell cycle and m-TOR signaling in 3T3-L1 cells, and its anti-adipogenic
      effect was found in a zebrafish model. 

PMID- 24560970
TI  - Retrograde intrarenal surgery vs extracorporeal shock wave lithotripsy for
      intermediate size inferior pole calculi: a prospective assessment of objective
      and subjective outcomes.
AB  - OBJECTIVE: To assess objective and subjective outcomes of retrograde intrarenal
      surgery (RIRS) and extracorporeal shock wave lithotripsy (SWL) for the treatment
      of intermediate size (1-2 cm) inferior calyceal (IC) stones in a prospective
      randomized fashion. METHODS: Between March 2011 and January 2013, 70 symptomatic
      adults who had isolated IC stone between 10 and 20 mm underwent RIRS or SWL by
      computer-generated pseudorandom assignment (1:1). Success rate, mean procedure
      time, hospital stay, pain score on day 1 and 2 using visual analog scale,
      analgesic requirement after discharge, complications, retreatment rate, auxiliary
      procedure, and patient-reported outcomes (using self-made nonvalidated
      questionnaire) were compared. RESULTS: Baseline parameters and mean stone size
      (SWL 16.45 +/- 2.28 mm, RIRS 15.05 +/- 3.56 mm; P = .0542) were comparable.
      Success rate was significantly higher after a single session of RIRS compared
      with 3 sessions of SWL (85% vs 54%; P = .008). Retreatment rate (65% vs 5.7%; P =
      .0001) and auxiliary procedure (45% vs 8%; P = .0009) were significantly higher
      in SWL. Pain score on postoperative day 1 and 2 was significantly higher in RIRS,
      but patients with SWL required significantly more analgesics afterward. Most of
      the complications were of Clavien grade I and/or II in both groups. Average time
      to return to normal activity and voiding symptoms were significantly higher in
      RIRS. Overall satisfaction score (2.17 +/- 1.24 vs 2.82 +/- 1.17; P = .026) was
      significantly higher in RIRS than SWL. CONCLUSION: For the treatment of
      intermediate size IC calculi, RIRS is superior to SWL in terms of objective and
      subjective outcomes.

PMID- 24560972
TI  - Editorial comment.

PMID- 24560971
TI  - Reproductive history and progression of lower urinary tract symptoms in women:
      results from a population-based cohort study.
AB  - OBJECTIVE: To examine whether reproductive history and related conditions are
      associated with the development and persistence of lower urinary tract symptoms
      (LUTS) other than urinary incontinence in a racially and/or ethnically diverse
      population-based sample of women. MATERIALS AND METHODS: The Boston Area
      Community Health Survey enrolled 3201 women aged 30-79 years of black, Hispanic,
      or white race and/or ethnicity. Baseline and 5-year follow-up interviews were
      completed by 2534 women (conditional response rate, 83.4%). The association
      between reproductive history factors and population-weighted estimates of LUTS
      progression and persistence was tested using multivariable logistic regression
      models. RESULTS: Between baseline and 5-year follow-up, 23.9% women had LUTS
      progression. In age-adjusted models, women who had delivered >=2 childbirths had
      higher odds of LUTS progression, but the association was completely accounted for
      by vaginal child delivery (eg, 2 vaginal childbirths vs none, multivariable
      adjusted odds ratio = 2.21; 95% CI, 1.46-3.35; P <.001). No increased odds of
      LUTS progression were found for women with only 1 vaginal delivery or who only
      had cesarean section(s). Uterine prolapse was associated with higher odds of LUTS
      progression (multivariable-adjusted odds ratio = 3.05; 95% CI, 1.43-6.50; P =
      .004). Gestational diabetes was associated with approximately twice the odds of
      LUTS progression, but only among younger women (interaction P = .003).
      CONCLUSION: In this cohort study, >=2 vaginal child deliveries, uterine prolapse,
      and among younger women, gestational diabetes were robust predictors of LUTS
      progression. Clinicians should assess the presence of bothersome urinary
      frequency, urgency, and voiding symptoms among women who have had multiple
      vaginal childbirths or gestational diabetes.

PMID- 24560973
TI  - Organ preservation technique without ischemia in patients with testicular tumor.
AB  - OBJECTIVE: To determine the safety and efficacy of organ-sparing surgery (OSS)
      without ischemia in patients with testicular tumor. METHODS: From January 2003 to
      October 2010, marker-negative clinical stage I testicular tumors <= 30 mm and
      marker-positive tumors in case of a tumor in a singular testis were managed by an
      organ-sparing approach. After localization of the tumor by ultrasound and
      accurate staging, OSS was performed without ischemia. Frozen section analyses of
      the tumor and tumor bed biopsies were obtained. In cases of malignant germ cell
      tumor with a normal contralateral testis, an orchiectomy of the tumor-bearing
      testis was performed. In all other cases, the organ-preserving procedure was
      completed. RESULTS: A total of 65 patients underwent this approach. In 35
      patients with a germ cell tumor on frozen section report (mean tumor size 1.4 cm;
      standard deviation +/- 8.54 mm) and presence of a normal contralateral testis, a
      radical orchiectomy of the tumor-bearing testis was performed. Thirty-three organ
      preserving procedures were completed in 30 patients without any complications
      (mean tumor size 0.9 cm; range, 0.2-2.0). No local or systemic recurrence was
      observed in all the 65 patients, and serum testosterone levels remained within
      normal limits in all but 2 patients. All patients are currently free of disease
      at a median follow-up of 52.5 months (range, 3-107). CONCLUSION: Our findings
      suggest that a "no-clamping" OSS technique is safe and feasible in selected tumor
      patients.

PMID- 24560975
TI  - Comparison of laparoscopic and percutaneous cryoablation for treatment of renal
      masses.
AB  - OBJECTIVE: To compare perioperative and oncologic outcomes between laparoscopic
      (LCA) and percutaneous cryoablation (PCA) and identify predictors of treatment
      failure after cryoablation. METHODS: Retrospective analysis was performed on 145
      patients undergoing LCA and 118 patients undergoing PCA at our institution
      between July 2000 and June 2011. RESULTS: LCA and PCA were performed on 167 and
      123 tumors, respectively. Perioperative complication rates were 10% for both the
      groups. Mean length of stay was significantly shorter for the PCA group (2.1 +/-
      0.5 vs 3.5 +/- 3.1 days, P <.01). Both groups had a comparable decline in
      estimated glomerular filtration rate at most recent follow-up (LCA 3.8 +/- 18.5
      mL/min/1.73 m(2) vs PCA 6.6 +/- 17.1 mL/min/1.73 m(2), P = .21). Mean oncologic
      follow-up was 71.4 +/- 32.1 months for LCA and 38.6 +/- 19.6 months for PCA.
      Kaplan-Meier estimated 5-year overall and recurrence-free survival were 79.3% and
      85.5%, respectively, for LCA and 86.3% and 86.3%, respectively, for PCA.
      Multivariate Cox proportional hazards analysis demonstrated that cryoablation
      approach (LCA vs PCA) was not predictive of overall mortality or disease
      recurrence (P = .36 and .82, respectively). Predictors of overall mortality
      included age-adjusted Charlson comorbidity index >= 6 (P = .01) and preoperative
      estimated glomerular filtration rate <60 mL/min/1.73 m(2) (P = .02). Predictors
      of recurrence included tumor size >= 3 cm (P <.01), body mass index >= 30 kg/m(2)
      (P = .01), and endophytic growth (P = .04). CONCLUSION: Mean length of stay was
      shorter for patients undergoing PCA as compared with LCA. Complication rates and
      decline in renal function at most recent follow-up were similar between groups.
      Oncologic outcomes were influenced by baseline patient and tumor characteristics
      rather than the cryoablation approach.

PMID- 24560976
TI  - Do active safety-needle devices cause spatter contamination?
AB  - Exposure to blood and body fluids is an occupational hazard in healthcare.
      Although the potential for blood-borne virus transmission through needlestick
      injury has been widely studied, the risk of this occurring through spatter
      contamination from safety-needle syringes is not well understood. This report
      examines this risk from three commonly used safety needles and suggests that this
      presents a new and significant hazard. Further work should be commissioned to
      quantify this hazard and determine which type of safety needle would minimize
      spatter contamination following syringe discharge and safety activation. 

PMID- 24560977
TI  - Improving the timeliness of meticillin-resistant Staphylococcus aureus
      antimicrobial decolonization therapy administration: a descriptive account.
AB  - BACKGROUND: It is important to ensure that the timely administration of
      appropriate antimicrobial decolonization therapy occurs when patients are
      identified as meticillin-resistant Staphylococcus aureus (MRSA)-colonized.
      Computerized Provider Order Entry (CPOE) with embedded Clinical Decision Support
      (CDS) may help to facilitate this. AIM: To investigate changes in the average
      time from patient admission to administration of MRSA decolonization
      antimicrobial therapy in the context of various national and local infection
      control interventions, including the use of CPOE. METHODS: Data concerning the
      time of admission and of administration of patients' first MRSA decolonization
      antimicrobials were extracted from a locally developed CPOE system (Prescribing
      Investigation and Communications System: PICS) which was introduced at a large
      university teaching hospital in the UK in 1998. Data were extracted
      retrospectively from January 2006 to March 2012. FINDINGS: A variety of relevant
      local and national interventions occurred from 2006 to 2012. Notably, the
      automatic charting of MRSA decolonization antimicrobial therapy was introduced in
      December 2007. There was a significant decline of 15.0% per year (95% confidence
      interval: 11.1-18.7%; P < 0.001) in the time taken from admission to
      administration of MRSA decolonization antimicrobial therapy during the study
      period. CONCLUSIONS: Numerous factors may have contributed to the observed
      reductions in the time from admission to administration of MRSA decolonization
      antimicrobials, including the implementation of specific features within a CPOE
      system. By rapidly attending to positive MRSA colonizations there is decreased
      potential for MRSA to spread, which may help to reduce the prevalence of MRSA
      colonizations within hospitals and improve patient outcomes.

PMID- 24560978
TI  - [Acute kidney injury in elderly patient: Diagnostic and therapeutic aspects].
AB  - Acute renal failure in elderly patient is a public health problem. It is worsen
      by physiological status and anatomical changes associated with age,
      polymedication and chronic diseases. The etiologies of acute renal failure in the
      elderly are the same as in adults. Their distribution is specific with a large
      proportion of obstructive acute renal failure. The diagnostic and therapeutic
      strategies are the same as for young adults; the injection of iodinated-contrast
      should be avoided. Therapeutic strategies are discussed in terms of quality of
      life pre-morbid. Age is not considered a determinant of intensive treatment
      decisions. Renal replacement therapy in the elderly is not associated with excess
      mortality. Prevention of acute renal failure should be a permanent concern. 

PMID- 24560979
TI  - [Relationship between dysphagia and malnutritition in patients over 65 years of
      age].
AB  - AIMS: The main objective of this study was to understand the relationship between
      oropharyngeal dysphagia, nutritional risk factors and functional impairment in
      the elderly (>65y) admitted to a medical-surgical hospital unit. Secondary
      objectives were to determine the prevalence of oropharyngeal dysphagia, the
      nutritional status and their functional capacity. METHODS: A cross-sectional
      observational study was performed. It included patients over 65 years of age
      admitted to the Gastroenterology-Urology Department in La Princesa University
      Hospital (Madrid, Spain) during the months of February and March. The following
      variables were recorded: age, sex, body mass index, family support, diagnosis,
      comorbidity, oropharyngeal dysphagia (EAT-10 and volume-viscosity evaluation
      method), malnutrition (Mininutritional Assessment) and functional capacity
      (Barthel index). RESULTS: A total of 167 patients were recruited, with 30.8% and
      15.4% prevalence of dysphagia and malnutrition, respectively. Prevalence of
      malnutrition increased to 75% in patients with oropharyngeal dysphagia. The
      logistic regression analysis showed how conditions as low score on the Barthel
      index (OR 0.97 [95% CI, 0.95-0.99]), comorbidity (OR 7.98 [CI 95%, 3.09-20.61])
      and dysphagia (OR 4.07 [CI 95%, 1.57-10.52]) were associated with a greater
      likelihood of suffering malnutrition. DISCUSSION: Oropharyngeal dysphagia is one
      of the most underdiagnosed and underestimated conditions among elderly patients
      and one that has a greater effect on their nutritional status. Accordingly, we
      suggest using established diagnostic methods with a multidisciplinary team
      collaboration for its early detection.

PMID- 24560980
TI  - [Effects of using an information leaflet in reducing perioperative anxiety and
      pain in patients undergoing urological surgery].
AB  - INTRODUCTION: The preoperative anxiety state is mainly caused by the fear of the
      circumstances surrounding the intervention. Anxiety causes increased
      postoperative pain, and a prolonged length of stay in hospital, which directly
      affect the cost of care. OBJECTIVE: To evaluate the effects of providing an
      anaesthesia information leaflet on postoperative anxiety and pain in patients
      undergoing urological surgery in the Miguel Servet Hospital. MATERIAL AND
      METHODS: A prospective quasi-experimental study of 100 cases, 51 of whom made up
      the intervention group who received the information leaflet, with the remaining
      49 cases being in the control group. The Hospital Anxiety and Depression Scale
      and the visual analogue scale for pain were assessed in both groups, before and
      after surgery. RESULTS: Of the 100 patients, 72% were male and 28% female, with
      an average age of 67.3 years (standard deviation, 9.7). In the intervention
      group, 21.6% showed anxiety before surgery and 0% in the postoperative period. In
      the control group 30.6% presented anxiety during the preoperative period and 4%
      in the postoperative period (chi(2) Pearson 5.20, P=.023). The study showed a
      direct relationship between preoperative anxiety and postoperative pain (chi(2)
      Pearson 10.519, P=.001). CONCLUSIONS: Good information about the surgical process
      reduces anxiety levels in the postoperative period.

PMID- 24560981
TI  - Comparative studies of Toll-like receptor signalling using zebrafish.
AB  - Zebrafish model systems for infectious disease are increasingly used for the
      functional analysis of molecular pattern recognition processes. These studies
      benefit from the high conservation level of all innate immune factors in
      vertebrates. Zebrafish studies are strategically well positioned for this because
      of the ease of comparisons with studies in other fish species of which the immune
      system also has been intensively studied, but that are currently still less
      amendable to detailed genetic or microscopic studies. In this paper we focus on
      Toll-like receptor (TLR) signalling factors, which currently are the best
      characterized in mammalian systems. We review the knowledge on TLR signalling in
      the context of recent advances in zebrafish studies and discuss possibilities for
      future approaches that can complement studies in cell cultures and rodent models.
      A focus in these comparisons is the role of negative control mechanisms in immune
      responses that appear very important in a whole organism to keep adverse systemic
      responses in check. We also pay much attention to comparisons with studies in
      common carp that is highly related to zebrafish and that because of its large
      body mass can complement immune studies in zebrafish. 

PMID- 24560983
TI  - Should oral implants be splinted in a mandibular implant-supported fixed complete
      denture? A 3-dimensional-model finite element analysis.
AB  - STATEMENT OF PROBLEM: The design of a mandibular fixed complete denture can
      influence periimplant bone loss. However, the design that transfers the greatest
      stress to the periimplant bone is not well documented. PURPOSE: The purpose of
      this study was to assess the stress distribution associated with splinted and
      nonsplinted implant-supported mandibular fixed complete denture designs. MATERIAL
      AND METHODS: Three-dimensional finite element models simulating 6 osseointegrated
      implants were created in the mandible to support a cobalt-chromium alloy and
      feldspathic porcelain veneering framework. One model simulated a 1-piece
      framework, and the other models simulated 2-piece and 3-piece frameworks. Axial
      and oblique loads were applied to the frameworks. RESULTS: For all the models,
      the greatest stress values were recorded in the periimplant bone of posterior
      implants, with differences between the left and right sides. The axial load
      transferred greater stress values to the periimplant bone than did the oblique
      load. The lowest periimplant bone stress values were observed in the 3-piece
      framework model at all implant locations, with the exception of implants placed
      in the canine region. CONCLUSIONS: A framework separated into 3 pieces transfers
      the least stress to the periimplant bone.

PMID- 24560982
TI  - An electrically coupled tissue-engineered cardiomyocyte scaffold improves cardiac
      function in rats with chronic heart failure.
AB  - BACKGROUND: Varying strategies are currently being evaluated to develop tissue
      engineered constructs for the treatment of ischemic heart disease. This study
      examines an angiogenic and biodegradable cardiac construct seeded with neonatal
      cardiomyocytes for the treatment of chronic heart failure (CHF). METHODS: We
      evaluated a neonatal cardiomyocyte (NCM)-seeded 3-dimensional fibroblast
      construct (3DFC) in vitro for the presence of functional gap junctions and the
      potential of the NCM-3DFC to restore left ventricular (LV) function in an in vivo
      rat model of CHF at 3 weeks after permanent left coronary artery ligation.
      RESULTS: The NCM-3DFC demonstrated extensive cell-to-cell connectivity after dye
      injection. At 5 days in culture, the patch contracted spontaneously in a rhythmic
      and directional fashion at 43 +/- 3 beats/min, with a mean displacement of 1.3 +/
      0.3 mm and contraction velocity of 0.8 +/- 0.2 mm/sec. The seeded patch could be
      electrically paced at nearly physiologic rates (270 +/- 30 beats/min) while
      maintaining coordinated, directional contractions. Three weeks after
      implantation, the NCM-3DFC improved LV function by increasing (p < 0.05) ejection
      fraction 26%, cardiac index 33%, dP/dt(+) 25%, dP/dt(-) 23%, and peak developed
      pressure 30%, while decreasing (p < 0.05) LV end diastolic pressure 38% and the
      time constant of relaxation (Tau) 16%. At 18 weeks after implantation, the NCM
      3DFC improved LV function by increasing (p < 0.05) ejection fraction 54%, mean
      arterial pressure 20%, dP/dt(+) 16%, dP/dt(-) 34%, and peak developed pressure
      39%. CONCLUSIONS: This study demonstrates that a multicellular,
      electromechanically organized cardiomyocyte scaffold, constructed in vitro by
      seeding NCM onto 3DFC, can improve LV function long-term when implanted in rats
      with CHF.

PMID- 24560984
TI  - The effects of post-core and crown material and luting agents on stress
      distribution in tooth restorations.
AB  - STATEMENT OF PROBLEM: Cement microfracture, post-and-core dislodgement, and tooth
      fracture are related to the mechanical properties and deformation of
      restorations. PURPOSE: The purpose of this study was to determine which
      combinations of post-and-core cements provide the most favorable stress
      distribution upon loading. MATERIAL AND METHODS: Three-dimensional models of
      teeth were created with the ANSYS program to simulate the different materials
      used for metal ceramic crowns (nickel-chromium, gold-palladium), posts and cores
      (Ti, Ni-Cr, Au-Pd), and cement (glass ionomer, composite resin, zinc phosphate,
      polycarboxylate, Panavia). Models were divided into 2 groups according to the
      alloys used in the crown restorations. A simulated masticatory force of 400 N was
      applied to the occlusal surface at a 45-degree inclination in the linguolabial
      direction to the long axis of the tooth, and von Mises equivalent stress values
      were calculated. RESULTS: The Ni-Cr metal ceramic crown/Au-Pd post-and-core/glass
      ionomer cement had the highest residual root von Mises equivalent stress value,
      whereas the Ni-Cr metal ceramic crown/Ni-Cr post-and-core/glass ionomer cement
      had the highest post stress value and the Ni-Cr metal ceramic crown/Au-Pd post
      and-core/zinc phosphate cement had the highest cement stress value. For each post
      and-core alloy, the stress values in the post and core were higher with Au-Pd
      metal ceramic crowns than with Ni-Cr metal ceramic crowns. The post-and-core
      material affected the amount of deformation. CONCLUSIONS: The use of a post-and
      core material with a lower elastic modulus and a cement with a higher elastic
      modulus led to a reduction in deformation in the residual root, cement, and post
      and core, and a reduction in stress in the post and core. The Ni-Cr metal ceramic
      crown/Au-Pd post-and-core/zinc phosphate cement or Panavia may therefore be
      favorable for post-and-core restorations.

PMID- 24560985
TI  - New device for the vitrification and in-straw warming of in vitro produced bovine
      embryos.
AB  - Two experiments were designed to test the use of a new device designed to vitrify
      and in-straw warm in vitro produced (IVP) embryos, which can potentially be used
      for their direct transfer to recipient females in field conditions. In experiment
      1, IVP embryos from both prepubertal and adult animals were vitrified on cryotops
      and warmed in steps (1, 0.5 and 0M sucrose; protocol W3) or directly in 0.5M
      (protocol W1/0.5) or 0M sucrose (protocol W1/0). Similar survival rates were
      recorded 24h after warming for calf embryos irrespective of the warming procedure
      (W3: 79.2%, W1/0.5: 62.5%, W1/0: 66.7%). For cow embryos, survival rates at 24h
      post-warming were significantly higher when embryos were warmed using the W3
      (85.7%) or W1/0.5 (89.1%) protocols compared to the W1/0 protocol (70.5%). In
      experiment 2, IVP embryos were vitrified on the new designed device followed by
      their in-straw cryoprotectant (0.5M sucrose) dilution/warming and different
      warming temperatures (45, 50, 60 and 70 degrees C) were tested. When warming
      solution passed through the new vitrification/warming device at 45 degrees C,
      61.5% of blastocysts were fully re-expanded or hatched at 24h post-warming, being
      not significantly different to the control (65%). Other warming temperatures
      triggered significantly lower survival rates at 24h post-warming. No significant
      differences were detected in total cell numbers and blastocyst apoptosis indices
      in response to vitrification followed by warming at 45 degrees C respect to the
      control. Our findings indicate that the new device allows vitrification and in
      straw warming of IVP bovine embryos, being a useful option for their direct
      transfer in field conditions.

PMID- 24560986
TI  - Influence of the sodium channel band on retinal ganglion cell excitation during
      electric stimulation--a modeling study.
AB  - Electric stimulation using retinal implants allows blind people to re-experience
      a rudimentary kind of vision. The elicited percepts or so called 'phosphenes' are
      highly inconstant and therefore do not restore vision properly. The better
      knowledge of how retinal neurons, especially retinal ganglion cells, respond to
      electric stimulation will help to develop more sophisticated stimulation
      strategies. Special anatomic and physiologic properties like a band of highly
      dense sodium channels in retinal ganglion cells may help to achieve a focal
      activation of target cells and as a result better restoration of vision. A
      portion of retinal ganglion cell axons, about 40MUm from the soma and between 25
      and 40MUm in length, shows a specific biophysical property. Electrode locations
      close to a band of highly dense sodium channels which were identified
      immunochemically show lowest thresholds during electric stimulation. The
      (modeled) thresholds for this kind of structure result in lowest thresholds as
      well. The influence on the location where action potentials are generated within
      the axon is far reaching. When a stimulating electrode is positioned far outside
      the actual band region the site of spike initiation still remains within the
      sodium channel band. These findings suggest to further examine the key mechanisms
      of activation for retinal ganglion cells because focal activation without
      influencing passing axons of neurons located far away can improve the outcome of
      electric stimulation and therefore the development of retinal implants. 

PMID- 24560987
TI  - Nitric oxide is necessary for long-term facilitation of synaptic responses and
      for development of context memory in terrestrial snails.
AB  - Correlated electrophysiological and behavioral experiments in the snail Helix
      lucorum were conducted to investigate the contribution of nitric oxide (NO) to
      synaptic plasticity during withdrawal reflex and aversive context memory
      development. Time, stimulation frequency and number of tetani/electrical shocks
      were determined in vitro and in vivo. In isolated brain preparations, nerve
      tetanization accompanied by bath application of serotonin induced long-term
      facilitation (LTF) of the excitatory postsynaptic potential (EPSP) in withdrawal
      interneurons. Bathing with either the NO-synthase inhibitor N-omega-nitro-L
      arginin (L-NNA) or the NO-scavenger 2-phenyl-4,4,5,5-tetramethyl-imidazoline-1
      oxyl 3-oxide (PTIO) before the tetanization prevented tetanus-induced long-term
      increase of EPSP. Withdrawal interneurons are key elements in the network
      underlying aversive behavior, with LTF considered the basis for aversive
      learning. We hypothesized that L-NNA injections in free-behaving snails could
      influence aversive learning. Snails were trained for 1 or 5days to remember the
      context in which they were shocked. In one-day training experiments, the snails
      received 5 electrical shocks in one context. Different groups of snails were sham
      injected or L-NNA-injected before or after training. After training, the sham
      injected groups demonstrated a significant increase in behavioral responses
      compared to the L-NNA-injected groups. On the following day, only sham-injected
      snails demonstrated altered behavioral responses, but no associative context
      differences were observed. These results correlated with the electrophysiological
      results. In another series of experiments, the snails received electrical shocks
      for 5days. Testing on the second day after training demonstrated that the sham
      injected group maintained selective aversive context memory, whereas the L-NNA
      injected snails were not different between the two contexts. Together these
      results demonstrated that inhibition of NO synthesis prevents memory formation
      and influences synaptic plasticity in the withdrawal interneurons that underlie
      the behavioral changes. This suggests that NO influences the behavior via
      regulation of synaptic plasticity. 

PMID- 24560988
TI  - [Lung cancer, how to deal with critical situations?].
AB  - The management of a patient with cancer, including lung cancer requires the
      investment of many health caregivers. The development of surgical techniques as
      well as targeted therapies requires a specialization of each. In order to
      optimize the actions of each, coordination of support is required from the
      diagnosis of cancer. This coordination can reduce iatrogenic toxicity and improve
      quality of life during the disease. It may also enhance quality of accompaniment
      of the patient, his family and a fortiori the health care team. The development
      of this coordination of supportive care in oncology, as part of a department of
      cancerology including care of patients with lung cancer is described. This
      organization allows to limit the toxicities of cancer treatment, but also to
      improve the suffering of patients by focusing on maintaining the patient at home.

PMID- 24560989
TI  - Solution NMR conformation of glycosaminoglycans.
AB  - Nuclear magnetic resonance (NMR) spectroscopy has been giving a pivotal
      contribution to the progress of glycomics, mostly by elucidating the structural,
      dynamical, conformational and intermolecular binding aspects of carbohydrates.
      Particularly in the field of conformation, NOE resonances, scalar couplings,
      residual dipolar couplings, and chemical shift anisotropy offsets have been the
      principal NMR parameters utilized. Molecular dynamics calculations restrained by
      NMR-data input are usually employed in conjunction to generate glycosidic bond
      dihedral angles. Glycosaminoglycans (GAGs) are a special class of sulfated
      polysaccharides extensively studied worldwide. Besides regulating innumerous
      physiological processes, these glycans are also widely explored in the global
      market as either clinical or nutraceutical agents. The conformational aspects of
      GAGs are key regulators to the quality of interactions with the functional
      proteins involved in biological events. This report discusses the solution
      conformation of each GAG type analyzed by one or more of the above-mentioned
      methods. 

PMID- 24560990
TI  - Effects of SNP variants in the 17beta-HSD2 and 17beta-HSD7 genes and 17beta-HSD7
      copy number on gene transcript and estradiol levels in breast cancer tissue.
AB  - Breast cancers reveal elevated E2 levels compared to plasma and normal breast
      tissue. Previously, we reported intra-tumour E2 to be negatively correlated to
      transcription levels of 17beta-HSD2 but positively correlated to 17beta-HSD7.
      Here, we explored these mechanisms further by analysing the same breast tumours
      for 17beta-HSD2 and -7 SNPs, as well as 17beta-HSD7 gene copy number. Among the
      SNPs detected, we found the 17beta-HSD2 rs4445895_T allele to be associated with
      lower intra-tumour mRNA (p=0.039) and an elevated intra-tumour E2 level
      (p=0.006). In contrast, we found the 17beta-HSD7 rs1704754_C allele to be
      associated with elevated mRNA (p=0.050) but not to E2 levels in breast tumour
      tissue. Surprisingly, 17beta-HSD7 - gene copy number was elevated in 19 out of 46
      breast tumours examined. Elevated copy number was associated with an increased
      mRNA expression level (p=0.013) and elevated tumour E2 (p=0.025). Interestingly,
      elevated 17beta-HSD7 - gene copy number was associated with increased expression
      not only of 17beta-HSD7, but the 17beta-HSD7_II pseudogene as well (p=0.019).
      Expression level of 17beta-HSD7 and its pseudogene was significantly correlated
      both in tumour tissue (rs=0.457, p=0.001) and in normal tissue (rs=0.453,
      p=0.002). While in vitro transfection experiments revealed no direct impact of
      17beta-HSD7 expression on pseudogene level, the fact that 17beta-HSD7 and 17beta
      HSD7_II share a 95.6% sequence identity suggests the two transcripts may be
      subject to common regulatory mechanisms. In conclusion, genetic variants of
      17beta-HSD2 and 17beta-HSD7 may affect intra-tumour gene expression as well as
      breast cancer E2 levels in postmenopausal women. 

PMID- 24560991
TI  - Mechanisms of early and delayed stroke after systematic off-pump coronary artery
      bypass.
AB  - BACKGROUND/PURPOSE: Stroke is one of the most devastating complications after
      cardiac surgery. Off-pump coronary artery bypass (OPCAB) has been reported to
      offer a lower risk of stroke. However, limited information was available on
      timing and mechanisms of stroke after OPCAB. We sought to assess the incidence,
      timing, and mechanisms of stroke after OPCAB. METHODS: A retrospective review of
      1010 patients undergoing systematic OPCAB between 2001 and 2012. Stroke was
      defined as any focal or global neurologic deficits lasting for more than 24
      hours. Stroke was classified as early stroke when it occurred less than 24 hours
      postoperatively, and delayed stroke when it occurred more than 24 hours
      postoperatively. Stroke mechanisms were classified as embolic or hypoperfusion.
      RESULTS: In a total of 10 patients (1.0%) 11 episodes of stroke developed after
      OPCAB. Early stroke occurred in five (0.5%) patients and delayed stroke occurred
      in six (0.6%) patients. Of five early strokes, the mechanisms were embolic in two
      (40%) and hypoperfusion in three (60%). Of six delayed strokes, the mechanisms
      were embolic in five (83%) and unknown in one. Of six delayed strokes, all the
      patients had diabetes mellitus and acute cardiac events prior to surgery, and
      five patients had postoperative atrial fibrillation. CONCLUSION: The incidence of
      stroke after systematic OPCAB was low. Early and delayed strokes were equally
      distributed. Stroke mechanisms were predominantly embolic. Early and delayed
      stroke differed in their mechanisms. Early and delayed stroke should be
      considered as two separate entities and different preventive strategies should be
      applied in future intervention.

PMID- 24560992
TI  - Oxidative stress and mitochondrial dysfunction in aluminium neurotoxicity and its
      amelioration: a review.
AB  - Aluminium is light weight and toxic metal present ubiquitously on earth which has
      gained considerable attention due to its neurotoxic effects. The widespread use
      of products made from or containing aluminium is ensuring its presence in our
      body. There is prolonged retention of a fraction of aluminium that enters the
      brain, suggesting its potential for accumulation with repeated exposures. There
      is no known biological role for aluminium within the body but adverse
      physiological effects of this metal have been observed in mammals. The generation
      of oxidative stress may be attributed to its toxic consequences in animals and
      humans. The oxidative stress has been implicated in pathogenesis of various
      neurodegenerative conditions including Alzheimer's disease and Parkinson's
      disease. Though it remains unclear whether oxidative stress is a major cause or
      merely a consequence of cellular dysfunction associated with neurodegenerative
      diseases, an accumulating body of evidence implicates that impaired mitochondrial
      energy production and increased mitochondrial oxidative damage is associated with
      the pathogenesis of neurodegenerative disorders. Being involved in the production
      of reactive oxygen species, aluminium may impair mitochondrial bioenergetics and
      may lead to the generation of oxidative stress. In this review, we have discussed
      the oxidative stress and mitochondrial dysfunctions occurring in Al
      neurotoxicity. In addition, the ameliorative measures undertaken in aluminium
      induced oxidative stress and mitochondrial dysfunctions have also been
      highlighted. 

PMID- 24560993
TI  - Selenium exposure and depressive symptoms: the Coronary Artery Risk Development
      in Young Adults Trace Element Study.
AB  - Selenium is an essential trace element important to neurotransmission, but toxic
      at high levels. Some studies suggest beneficial effects on mood. We assessed the
      association of selenium exposure with presence of depressive symptoms. Selenium
      exposure was measured in toenail samples collected in 1987 from 3735 US
      participants (age 20-32 years) and depressive symptoms assessed in 1990, 1995,
      2000, 2005, and 2010 using the Center for Epidemiologic Studies Depression Scale
      (CES-D). Binary and polytomous logistic regression models were used to assess the
      relation of log2(selenium) and selenium quintiles with presence of depressive
      symptoms (CES-D score>=27 or on antidepressant medication). Relative to selenium
      quintile 1, the adjusted odds ratio (OR) for having depressive symptoms in 1990
      for quintile 5 was 1.59 (95% CI: 1.01, 2.51) and a unit increase in
      log2(selenium), which represents a doubling of the selenium level, was associated
      with an OR=2.03 (95% CI: 1.12, 3.70). When examining 1, 2 or 3+ exams vs. no
      exams with symptoms, the OR for quintile 5 was 1.73 (1.04, 2.89) for 3+ exams and
      for one exam and two exams, there were no associations. In a generalized
      estimating equations longitudinal model, a doubling of the selenium level was
      associated with a 56% higher odds of having depressive symptoms at an exam.
      Contrary to previously reported findings related to mood, higher level of
      selenium exposure was associated with presence of elevated depressive symptoms.
      More research is needed to elucidate the role of selenium in depressive
      disorders. 

PMID- 24560994
TI  - The Argus II Retinal Prosthesis: 12-month outcomes from a single-study center.
AB  - PURPOSE: To study the anatomic and functional outcomes of Argus II Retinal
      Prosthesis System implantation in patients with retinitis pigmentosa. DESIGN:
      Interventional case series. METHODS: The study population included 6 patients
      with visual acuity no better than light perception. After the Argus II Retinal
      Prosthesis System was implanted, complications and anatomic and functional
      results were studied. The main outcome measures were mobility, square
      localization, direction of motion, grating visual acuity, and Goldmann visual
      field, all of which were assessed. Optical coherence tomography was performed.
      RESULTS: Implantation of the Argus II Retinal Prosthesis System was safely
      performed in all patients. One patient experienced postoperative elevation in
      intraocular pressure, which was controlled medically. In 1 patient, moderate
      detachment of the choroid occurred postoperatively, and it resolved
      spontaneously. One patient withdrew from the study. Wound dehiscence,
      endophthalmitis or retinal detachment was not observed. All patients were able to
      locate a bright light on the ceiling and a dark line on the floor after the
      surgery. Performance in square localization tests improved in 4 patients, and
      direction of motion improved in 3 patients. One patient achieved grating visual
      acuity. Goldmann visual field test results improved in all patients. CONCLUSIONS:
      The patients showed improvement in visual tasks after the surgery, and the device
      was well tolerated and functional over a 1-year follow-up period. A rigorous
      patient-selection process is necessary to maximize patient compliance with the
      rigorous follow-up testing schedule. Both patients and medical staff should be
      prepared for a lengthy, arduous rehabilitation process.

PMID- 24560996
TI  - [Notes on real and daily cost-efficiency].

PMID- 24560995
TI  - Wavefront-guided versus wavefront-optimized laser in situ keratomileusis for
      patients with myopia: a prospective randomized contralateral eye study.
AB  - PURPOSE: To compare the clinical outcomes of wavefront-guided and wavefront
      optimized laser in situ keratomileusis (LASIK). DESIGN: Prospective, randomized,
      fellow-eye-controlled study. METHODS: The setting was a single academic
      institution. The study population included 110 eyes of 55 patients with myopia
      with and without astigmatism. One eye of each patient was randomized to undergo
      wavefront-guided LASIK by the AMO Visx CustomVue S4 IR excimer laser system; the
      fellow eye received wavefront-optimized LASIK by the Alcon Allegretto Wave Eye-Q
      400 Hz excimer laser system. Corneal flaps were constructed using the Intralase
      FS 60 Hz femtosecond laser. Patients were followed at postoperative months 1, 3,
      6, and 12. The study's main outcome measures were uncorrected visual acuity,
      stability of refractive correction, contrast sensitivity, and wavefront
      aberrometry. RESULTS: After 12 months, LASIK eyes had achieved visual acuity of
      20/12.5 or better (30 eyes, 56%) in the wavefront-guided group compared to those
      receiving wavefront-optimized treatment (22 eyes, 41%) (P = 0.016). Average
      spherical equivalent refractions were -0.13 +/- 0.46 diopters in wavefront-guided
      eyes whereas in wavefront-optimized eyes the refractions were -0.41 +/- 0.38
      diopters at 12 months. Wavefront-guided eyes also achieved better best-corrected
      visual acuity at both the 5% and 25% contrast levels (P = 0.022 and P = 0.004,
      respectively). There were no differences in levels of residual astigmatism (P =
      0.798) or in higher order aberrations (P = 0.869). CONCLUSIONS: Both wavefront
      guided and wavefront-optimized treatments are able to correct myopia safely and
      effectively in eyes with and without astigmatism. However, wavefront-guided
      treatment platforms appear to offer significant advantages in terms of residual
      refractive error, uncorrected distance acuity and contrast sensitivity.

PMID- 24560997
TI  - nab-Paclitaxel in combination with biologically targeted agents for early and
      metastatic breast cancer.
AB  - Taxanes are highly active chemotherapeutic agents used in the treatment of early
      stage and metastatic breast cancer. Novel formulations have been developed to
      improve efficacy and decrease toxicity associated with these cytotoxic agents.
      nab-Paclitaxel is a biologically interactive, solvent-free, 130-nm-sized albumin
      bound paclitaxel, developed to avoid the Cremophor vehicle used in solvent-based
      paclitaxel. Based on a pivotal phase 3 study, nab-paclitaxel was shown to be
      safely infused at a significantly higher dose of paclitaxel than the doses used
      with standard paclitaxel therapy, and had a shorter infusion time, no
      premedication, and higher response rates. It is now approved in the United States
      for treatment of breast cancer after failure of combination chemotherapy for
      metastatic disease or relapse within 6 months of adjuvant therapy, and has
      demonstrated promising efficacy and favorable tolerability. Recently, several
      phase 2 and 3 studies have suggested a role for nab-paclitaxel in combination
      with biologically targeted agents for the treatment of early- and late-stage
      breast cancer. This review will discuss the findings of clinical trials
      evaluating nab-paclitaxel in combination with biologically targeted therapeutic
      agents for breast cancer in the neoadjuvant, adjuvant, and metastatic settings.

PMID- 24560998
TI  - Longitudinal neurochemical modifications in the aging mouse brain measured in
      vivo by 1H magnetic resonance spectroscopy.
AB  - Alterations to brain homeostasis during development are reflected in the
      neurochemical profile determined noninvasively by (1)H magnetic resonance
      spectroscopy. We determined longitudinal biochemical modifications in the cortex,
      hippocampus, and striatum of C57BL/6 mice aged between 3 and 24 months . The
      regional neurochemical profile evolution indicated that aging induces general
      modifications of neurotransmission processes (reduced GABA and glutamate),
      primary energy metabolism (altered glucose, alanine, and lactate) and turnover of
      lipid membranes (modification of choline-containing compounds and
      phosphorylethanolamine), which are all probably involved in the frequently
      observed age-related cognitive decline. Interestingly, the neurochemical profile
      was different in male and female mice, particularly in the levels of taurine that
      may be under the control of estrogen receptors. These neurochemical profiles
      constitute the basal concentrations in cortex, hippocampus, and striatum of
      healthy aging male and female mice.

PMID- 24561001
TI  - Intranasal fentanyl versus fentanyl pectin nasal spray for the management of
      breakthrough cancer pain in doses proportional to basal opioid regimen.
AB  - The aim of this randomized, crossover, comparison study was to assess the
      analgesic and adverse effects of 2 nasal preparations, intranasal fentanyl (INFS)
      and fentanyl pectin nasal spray (FPNS), for breakthrough pain, given in doses
      proportional to opioid basal regimen. Each patient randomly received INFS or FPNS
      in doses proportional to opioid dosages used for background analgesia for 2 pairs
      of episodes. For each episode of breakthrough pain, pain intensity and adverse
      effects intensity were recorded just before starting the INFS or FPNS (T0) and 5
      minutes (T5), 10 minutes (T10), and 20 minutes (T20) after the administration of
      the nasal drugs. Sixty-nine patients were studied. The mean age was 63.4 years,
      and 37 patients were males. For the present analysis, 188 episodes were
      considered. A statistical decrease in pain intensity was observed with both nasal
      drugs after 5, 10, and 20 minutes. A decrease in pain intensity of >33% was
      observed in 16, 102, and 159 treated episodes at T5, T10, and T20, respectively.
      Adverse effects were of mild nature in most cases or were preexistent because of
      basal opioid therapy. No differences were found in summed pain intensity
      difference 20 minutes after dosing. Most of patients did not find substantial
      preferences. INFS and FPNS were effective and well-tolerated treatments for
      breakthrough pain management. Both delivery systems, in doses proportional to the
      basal opioid regimen, provided significant analgesia within 10 minutes, without
      producing relevant adverse effects. PERSPECTIVE: This article showed that INFS
      and FPNS in doses proportional to basal opioid regimen are equally safe and
      effective for the management of breakthrough pain in cancer patients. These data
      provide new insights on the use of nasal preparations of fentanyl.

PMID- 24561000
TI  - Emotional granularity and social functioning in individuals with schizophrenia:
      an experience sampling study.
AB  - Previous research has shown that healthy individuals who fail to differentiate
      among emotional states (i.e., those with low emotional granularity; EG) have
      poorer social functioning (SF) than those with high EG. It is unknown, however,
      whether these associations extend to clinical disorders characterized by impaired
      SF, such as schizophrenia. In the present study, we compared SF and EG in
      individuals with schizophrenia and healthy controls, and then, within the
      schizophrenia group, we examined the links between EG and SF. Employing an
      Experience Sampling Method approach, 77 individuals with schizophrenia and 27
      healthy controls rated their momentary emotions (sadness, anxiety, anger, and
      happiness) up to 10 times/day over a two-day period using mobile electronic
      devices. For each participant, we then calculated the within-subject average
      correlations among the momentary emotion ratings, producing two EG indices -
      EGIall for all emotions and EGIneg for negative ones. A subsample of participants
      with schizophrenia also completed self-report, interview, and ability-based
      measures of SF. Compared to healthy controls, individuals with schizophrenia
      displayed significantly poorer SF and lower EGIall, but comparable EGIneg. Within
      the schizophrenia group, hierarchical multiple regression analyses indicated that
      EGIall, but not EGIneg, significantly predicted social dysfunction after
      controlling for emotional awareness, symptoms, and emotional intensity and
      variability. Our findings indicate that individuals with schizophrenia have a
      relatively intact ability to differentiate among negative emotions in everyday
      life. However, they experience significant difficulties differentiating between
      positive and negative emotions, and this may contribute to their social
      difficulties. 

PMID- 24560999
TI  - Lhx1 is required in Mullerian duct epithelium for uterine development.
AB  - The female reproductive tract organs of mammals, including the oviducts, uterus,
      cervix and upper vagina, are derived from the Mullerian ducts, a pair of
      epithelial tubes that form within the mesonephroi. The Mullerian ducts form in a
      rostral to caudal manner, guided by and dependent on the Wolffian ducts that have
      already formed. Experimental embryological studies indicate that caudal
      elongation of the Mullerian duct towards the urogenital sinus occurs in part by
      proliferation at the ductal tip. The molecular mechanisms that regulate the
      elongation of the Mullerian duct are currently unclear. Lhx1 encodes a LIM
      homeodomain transcription factor that is essential for male and female
      reproductive tract development. Lhx1 is expressed in both the Wolffian and
      Mullerian ducts. Wolffian duct-specific knockout of Lhx1 results in degeneration
      of the Wolffian duct and consequently the non-cell-autonomous loss of the
      Mullerian duct. To determine the role of Lhx1 specifically in the Mullerian duct
      epithelium, we performed a Mullerian duct-specific knockout study using Wnt7a-Cre
      mice. Loss of Lhx1 in the Mullerian duct epithelium led to a block in Mullerian
      duct elongation and uterine hypoplasia characterized by loss of the entire
      endometrium (luminal and glandular epithelium and stroma) and inner circular but
      not the outer longitudinal muscle layer. Time-lapse imaging and molecular
      analyses indicate that Lhx1 acts cell autonomously to maintain ductal progenitor
      cells for Mullerian duct elongation. These studies identify LHX1 as the first
      transcription factor that is essential in the Mullerian duct epithelial
      progenitor cells for female reproductive tract development. Furthermore, these
      genetic studies demonstrate the requirement of epithelial-mesenchymal
      interactions for uterine tissue compartment differentiation. 

PMID- 24561002
TI  - The impact of homologous recombination repair deficiency on depleted uranium
      clastogenicity in Chinese hamster ovary cells: XRCC3 protects cells from
      chromosome aberrations, but increases chromosome fragmentation.
AB  - Depleted uranium (DU) is extensively used in both industry and military
      applications. The potential for civilian and military personnel exposure to DU is
      rising, but there are limited data on the potential health hazards of DU
      exposure. Previous laboratory research indicates DU is a potential carcinogen,
      but epidemiological studies remain inconclusive. DU is genotoxic, inducing DNA
      double strand breaks, chromosome damage and mutations, but the mechanisms of
      genotoxicity or repair pathways involved in protecting cells against DU-induced
      damage remain unknown. The purpose of this study was to investigate the effects
      of homologous recombination repair deficiency on DU-induced genotoxicity using
      RAD51D and XRCC3-deficient Chinese hamster ovary (CHO) cell lines. Cells
      deficient in XRCC3 (irs1SF) exhibited similar cytotoxicity after DU exposure
      compared to wild-type (AA8) and XRCC3-complemented (1SFwt8) cells, but DU induced
      more break-type and fusion-type lesions in XRCC3-deficient cells compared to wild
      type and XRCC3-complemented cells. Surprisingly, loss of RAD51D did not affect DU
      induced cytotoxicity or genotoxicity. DU induced selective X-chromosome
      fragmentation irrespective of RAD51D status, but loss of XRCC3 nearly eliminated
      fragmentation observed after DU exposure in wild-type and XRCC3-complemented
      cells. Thus, XRCC3, but not RAD51D, protects cells from DU-induced breaks and
      fusions and also plays a role in DU-induced chromosome fragmentation. 

PMID- 24561004
TI  - Effect of water fluoridation on the development of medial vascular calcification
      in uremic rats.
AB  - Public water fluoridation is a common policy for improving dental health.
      Fluoride replaces the hydroxyls of hydroxyapatite, thereby improving the strength
      of tooth enamel, but this process can also occur in other active calcifications.
      This paper studies the effects of water fluoridation during the course of
      vascular calcification in renal disease. The effect of fluoride was studied in
      vitro and in vivo. Rat aortic smooth muscle cells were calcified with 2mM Pi for
      5 days. Fluoride concentrations of 5-10 MUM--similar to those found in people who
      drink fluoridated water--partially prevented calcification, death, and osteogene
      expression in vitro. The anticalcifying mechanism was independent of cell
      activity, matrix Gla protein, and fetuin A expressions, and it exhibited an IC50
      of 8.7 MUM fluoride. In vivo, however, fluoridation of drinking water at 1.5mg/L
      (concentration recommended by the WHO) and 15 mg/L dramatically increased the
      incipient aortic calcification observed in rats with experimental chronic kidney
      disease (CKD, 5/6-nephrectomy), fed a Pi-rich fodder (1.2% Pi). Fluoride further
      declined the remaining renal function of the CKD animals, an effect that most
      likely overwhelmed the positive effect of fluoride on calcification in vitro.
      Ultrastructural analysis revealed that fluoride did not modify the Ca/P atomic
      ratio, but it was incorporated into the lattice of in vivo deposits. Fluoride
      also converted the crystallization pattern from plate to rode-like structures. In
      conclusion, while fluoride prevents calcification in vitro, the WHO's recommended
      concentrations in drinking water become nephrotoxic to CKD rats, thereby
      aggravating renal disease and making media vascular calcification significant.

PMID- 24561005
TI  - Inhibitory potency of 4-carbon alkanes and alkenes toward CYP2E1 activity.
AB  - CYP2E1 has been implicated in the bioactivation of many small molecules into
      reactive metabolites which form adducts with proteins and DNA, and thus a better
      understanding of the molecular determinants of its selectivity are critical for
      accurate toxicological predictions. In this study, we determined the potency of
      inhibition of human CYP2E1 for various 4-carbon alkanes, alkenes and alcohols. In
      addition, known CYP2E1 substrates and inhibitors including 4-methylpyrazole,
      aniline, and dimethylnitrosamine were included to determine their relative
      potencies. Of the 1,3-butadiene-derived metabolites studied, 3,4-epoxy-1-butene
      was the strongest inhibitor with an IC50 of 110 MUM compared to 1700 MUM and 6600
      MUM for 1,2-butenediol and 1,2:3,4-diepoxybutane, respectively. Compared to known
      inhibitors, inhibitory potency of 3,4-epoxy-1-butene is between 4-methylpyrazole
      (IC50 = 1.8 MUM) and dimethylnitrosamine (IC50 = 230 MUM). All three butadiene
      metabolites inhibit CYP2E1 activity through a simple competitive mechanism. Among
      the 4-carbon compounds studied, the presence and location of polar groups seems
      to influence inhibitory potency. To further examine this notion, the
      investigation was extended to include structurally and chemically similar
      analogues, including propylene oxide and various butane alcohols. Those results
      demonstrated preferential recognition of CYP2E1 toward the type and location of
      polar and hydrophobic structural elements. Taken together, CYP2E1 metabolism may
      be modified in vivo by exposure to 4-carbon compounds, such as drugs, and
      nutritional constituents, a finding that highlights the complexity of exposure to
      mixtures.

PMID- 24561006
TI  - Gram-scale purification of dehydroevodiamine from Evodia rutaecarpa fruits, and a
      procedure for selective removal of quaternary indoloquinazoline alkaloids from
      Evodia extracts.
AB  - Dehydroevodiamine (DHE) is a major bioactive constituent in the traditional
      Chinese herbal drug Evodiae fructus (Wu zhu yu). The compound has been shown to
      possess pronounced cardiovascular and neuropharmacological activities in vitro
      and in vivo. For quality control purposes and follow-up studies assessing
      potential safety risks of DHE, we developed a simple and efficient two-step
      protocol for gram-scale purification of DHE. An alkaloidal fraction was obtained
      by cation-exchange solid phase extraction, and DHE and the minor alkaloid
      hortiamine were purified by isocratic preparative RP-HPLC. The DHE content in
      different commercial batches of Evodiae fructus, and in a series of commercially
      available Evodia-containing TCM products was assessed. A daily intake of up to mg
      amounts of DHE was calculated from recommended doses of these products. A method
      for the selective removal of quaternary indoloquinazoline alkaloids from Evodia
      extracts was developed. 

PMID- 24561003
TI  - Astrocytes protect against diazinon- and diazoxon-induced inhibition of neurite
      outgrowth by regulating neuronal glutathione.
AB  - Evidence demonstrating that human exposure to various organophosphorus
      insecticides (OPs) is associated with neurobehavioral deficits in children
      continues to emerge. The present study focused on diazinon (DZ) and its active
      oxygen metabolite, diazoxon (DZO), and explored their ability to impair neurite
      outgrowth in rat primary hippocampal neurons as a mechanism of developmental
      neurotoxicity. Both DZ and DZO (0.5-10 MUM) significantly inhibited neurite
      outgrowth in hippocampal neurons, at concentrations devoid of any cyototoxicity.
      These effects appeared to be mediated by oxidative stress, as they were prevented
      by antioxidants (melatonin, N-t-butyl-alpha-phenylnitrone, and glutathione ethyl
      ester). Inhibition of neurite outgrowth was observed at concentrations below
      those required to inhibit the catalytic activity of acetylcholinesterase. The
      presence of astrocytes in the culture was able to provide protection against
      inhibition of neurite outgrowth by DZ and DZO. Astrocytes increased neuronal
      glutathione (GSH) in neurons, to levels comparable to those of GSH ethyl ester.
      Astrocytes depleted of GSH by L-buthionine-(S,R)-sulfoximine no longer conferred
      protection against DZ- and DZO-induced inhibition of neurite outgrowth. The
      findings indicate that DZ and DZO inhibit neurite outgrowth in hippocampal
      neurons by mechanisms involving oxidative stress, and that these effects can be
      modulated by astrocytes and astrocyte-derived GSH. Oxidative stress from other
      chemical exposures, as well as genetic abnormalities that result in deficiencies
      in GSH synthesis and regulation, may render individuals more susceptible to these
      developmental neurotoxic effects of OPs.

PMID- 24561007
TI  - Coumarinoids from the fruits of Micromelum falcatum.
AB  - Four new compounds, microminutin B (1), microminutin C (2), micromarinate (3),
      and secomicromelin (4) as well as 17 known compounds were isolated from the
      fruits of Micromelum falcatum. All compounds were evaluated for antifungal
      activity against Pythium insidiosum using disc diffusion assay. P. insidiosum is
      a fungus-like microorganism for which antifungal agents now available are not
      effective. The results show that four compounds including secomicromelin (4), 7
      methoxy-8-(4'-methyl-3'-furanyl)coumarin (10), micromarin B (17), and
      isomicromelin (19) could inhibit the mycelia growth of P. insidiosum. 

PMID- 24561008
TI  - Four new eudesmane-type sesquiterpenes from the basal leaves of Salvia plebeia R.
      Br.
AB  - Four new eudesmane-type sesquiterpenes, named plebeiolide A-C (1-3) and
      plebeiafuran (4), together with a known eudesmanolide (5), were isolated from the
      basal leaves of Salvia plebeia R. Br. Their structures were elucidated by
      extensive spectroscopic analysis including 1D and 2D NMR, HR-ESI-MS spectra. The
      absolute configuration of compound 1 was confirmed by single-crystal X-ray
      analysis and CD spectra. The inhibitory activity of isolated compounds toward NO
      production in lipopolysaccharide-induced RAW264.7 cells was evaluated and
      compounds 3 and 4 showed moderate inhibitory activity. In addition, the
      sesquiterpene lactones in Lamiaceae plants may possess some chemosystematic
      implications at intergeneric and intrageneric levels. 

PMID- 24561009
TI  - Left ventricular lead position and outcomes in the Resynchronization
      Defibrillation for Ambulatory Heart Failure Trial (RAFT).
AB  - BACKGROUND: Conflicting data exist regarding the association between left
      ventricular (LV) lead position and benefit from cardiac resynchronization
      therapy. We evaluated the relationships between LV lead positions and the risk of
      death or hospitalization for heart failure (HF) in the cardiac resynchronization
      therapy arm of the Resynchronization-Defibrillation for Ambulatory Heart Failure
      Trial (RAFT). METHODS: LV lead position was categorized by site investigator (MD)
      and in a chest radiograph core laboratory (CXR) as "anterior," "lateral," or
      "posterior" in the short axis, and "basal," "mid," or "apical" in the long axis.
      Agreement between MD and CXR LV lead position classification was evaluated and
      the independent relationship between LV lead position and clinical outcome was
      assessed using Cox multivariable models. RESULTS: Agreement between MD and CXR LV
      lead position was poor (kappa <= 0.26). Over 39 +/- 20 months, 140 of 447 (31.3%)
      patients met the RAFT primary end point (death or HF hospitalization). In
      adjusted analyses, neither MD-determined nor CXR-determined anterior or apical LV
      lead position was significantly associated with the primary outcome. However, CXR
      defined apical LV lead position was associated with a higher risk of HF
      hospitalization (hazard ratio, 1.99; P = 0.004). CONCLUSIONS: Poor agreement
      between implanting physician and core lab CXR-based categorizations of LV lead
      position was observed. Neither categorization method resulted in significant
      associations between apical or anterior LV lead position and the risk of the
      composite primary outcome of death or heart failure hospitalization. However, CXR
      defined apical lead position was associated with increased risk of HF
      hospitalization.

PMID- 24561010
TI  - Intensive lifestyle intervention improves cardiometabolic and exercise parameters
      in metabolically healthy obese and metabolically unhealthy obese individuals.
AB  - BACKGROUND: The effects of an intensive lifestyle intervention including
      Mediterranean diet nutritional counselling and high-intensity interval training
      (HIIT) on body composition, cardiometabolic, and exercise parameters were studied
      in metabolically unhealthy obese (NMHO) and metabolically healthy but obese (MHO)
      subjects. METHODS: Fifty-five MHO (51 +/- 8 years; waist circumference, 109 +/-
      13 cm) and 79 NMHO subjects (54 +/- 9 years; waist circumference, 112 +/- 13 cm)
      participated in an intensive lifestyle modification program based on
      Mediterranean diet nutritional counselling and HIIT 2-3 times per week. Body
      composition, cardiometabolic, and exercise parameters were measured at baseline
      and after 9 months. RESULTS: Initially, MHO patients had a lower blood pressure
      (BP), fasting glycemia, triglycerides, and a higher high-density lipoprotein
      cholesterol and peak oxygen uptake (VO2 peak) (P < 0.05) vs NMHO patients. Body
      mass (P < 0.05), waist circumference (P < 0.0001), total and trunk fat mass (P <
      0.001), systolic and diastolic BP (P < 0.001), fasting glucose (P < 0.0001),
      insulin sensitivity (P < 0.05), VO2 peak and muscle endurance (P < 0.0001) were
      similarly improved in both groups after the program. Prevalence of NMHO was
      reduced by 17.91% (P < 0.01) after the program. Similar improvements in body
      composition, BP, and exercise parameters were found for MHO and NMHO men and
      women (P < 0.05). In all patients, improvement of VO2 peak was negatively
      correlated with improvements in body composition, systolic blood pressure, and
      resting heart rate (HR) (R = -0.61 to -0.24; P < 0.05). CONCLUSIONS: A long-term
      intensive lifestyle program including Mediterranean diet nutritional counselling
      and HIIT is an appropriate intervention in MHO and NMHO subjects with similar
      potential clinical health benefits including an improved body composition, BP,
      fasting glycemia, insulin sensitivity, VO2 peak, and muscle endurance.

PMID- 24561011
TI  - It is urgent to investigate predictors of the response of blood pressure to renal
      denervation.

PMID- 24561012
TI  - Plaque rupture within a 16-year-old, bare-metal coronary stent.

PMID- 24561013
TI  - Evidence for autophagic gridlock in aging and neurodegeneration.
AB  - Autophagy is essential to neuronal homeostasis, and its impairment is implicated
      in the development of neurodegenerative pathology. However, the underlying
      mechanisms and consequences of this phenomenon remain a matter of conjecture. We
      show that misexpression of human tau in Drosophila induces accumulation of
      autophagic intermediates with a preponderance of large vacuoles, which we term
      giant autophagic bodies (GABs), which are reminiscent of dysfunctional autophagic
      entities. Lowering basal autophagy reduces GABs, whereas increasing autophagy
      decreases mature autolysosomes. Induction of autophagy is also associated with
      rescue of the tauopathy phenotype, suggesting that formation of GABs may be a
      compensatory mechanism rather than a trigger of neurodegeneration. Last, we show
      that the peculiar Biondi bodies observed in the choroid epithelium of both
      elderly and Alzheimer's disease human brains express immunoreactive markers
      similar to those of GABs. Collectively, these data indicate that autophagic
      gridlock contributes to the development of pathology in aging and
      neurodegeneration.

PMID- 24561014
TI  - Immunophenotyping of peripheral immunoregulatory as well as Th17A and Th22 cell
      subpopulations in kidney transplant recipients under belatacept or cyclosporine
      treatment.
AB  - OBJECTIVE: Regulatory Foxp3-expressing T cells (Tregs), IL-10-producing B cells
      (Bregs), and IDO-expressing dendritic cells (DCregs) downregulate inflammatory
      processes and induce peripheral tolerance, while Th17A and Th22 cell
      subpopulations are of proinflammatory nature. The aims of the study were to
      characterize and to enumerate peripheral Tregs, Bregs, and DCregs and Th17A and
      Th22 cell subpopulations in kidney transplant recipients (KTRs) under belatacept
      or cyclosporine treatment. METHODS: Forty-one KRT patients (30 under belatacept
      treatment and 11 under cyclosporine treatment) and 26 healthy donors (HDs) were
      included in the study. CD19(+)-expressing peripheral B lymphocytes were purified
      by positive selection. IL-10-producing B cells, CD4(+)/CD25(high)Foxp3(+), and
      CD8(+)/CD28(-)Foxp3(+) Tregs, CCR6(+)/CD123(+)/IDO(+) DCs, as well as Th17A and
      Th22 cell subpopulations were quantitated by flow cytometry. RESULTS: Of the IL
      10-producing Bregs, CD19(+)/CD24(high)/CD38(high)/CD5(+),
      CD19(+)/CD24(high)/CD38(high)/CD10(+), CD19(+)/CD24(high)/CD38(high)/CD20(+), and
      CD19(+)/CD24(high)/CD38(high)/CD27(-) had significant higher frequency in
      patients under belatacept treatment when compared with those under cyclosporine.
      Only CD19(+)/CD24(high)/CD38(high)/CD27(+) and
      CD19(+)/CD24(high)/CD38(high)/CXCR7(+) cells had significant higher frequency in
      patients under cycloporine treatment when compared to those under belatacept. The
      percentages of IDO-expressing pDC, CD4(+)/CD25(high)Foxp3(+), and CD8(+)/CD28(
      )Foxp3(+) were significantly higher in the belatacept group when compared the
      cyclosporine one, while Th17A and Th22 cells had significant higher frequency in
      the latter group. CONCLUSION: Belatacept seems to maintain and enhance, at least
      systemically, a tolerant profile to renal allograft in transplant recipients by
      means of higher circulatory frequencies of regulatory B, T and pDC
      subpopulations.

PMID- 24561015
TI  - The contribution of emotional maltreatment to alcohol dependence in a treatment
      seeking sample.
AB  - Studies reporting a link between child maltreatment and addiction have typically
      focused on physical and sexual abuse. In contrast, emotional maltreatment has
      rarely been studied in substance-abusing samples although it is associated with a
      wide range of dysfunction. The current study aimed to determine the specific
      impact of different types of maltreatment and peer victimization on alcohol
      dependence and to examine the potentially mediating role of psychopathology. A
      sample of treatment seeking adults with alcohol dependence (N=72) underwent an
      extensive clinical examination including both a standardized interview and self
      report measures. Child maltreatment, peer victimization, severity of alcohol
      dependence, and general psychopathology were assessed. Regression analyses
      revealed that emotional maltreatment was the strongest predictor of alcohol
      dependence severity whereas a unique contribution of peer victimization was not
      found. Our findings suggest that emotional maltreatment might have a major role
      in the etiology of AD that seems to exceed the contribution of other abuse and
      victimization experiences. Thereby, the study underscores the need for
      considering child maltreatment experiences in the prevention and treatment of AD.

PMID- 24561016
TI  - Psychostimulant use among college students during periods of high and low stress:
      an interdisciplinary approach utilizing both self-report and unobtrusive chemical
      sample data.
AB  - This study quantified psychostimulant use patterns over periods of high and low
      stress from both self-report measures and chemical wastewater analyses and
      identified possible predictors of psychostimulant abuse on a college campus. Self
      report data were collected at three times of varying stress levels throughout one
      college semester: during the first week of school (N=676), midterms (N=468), and
      shortly before final exams (N=400). Campus wastewater samples were collected over
      72-hour periods during the same time frames as the surveys. The metabolites of
      Adderall and Ritalin were quantified through solid phase extraction and liquid
      chromatography-tandem mass spectrometry (LC-MS/MS). Samples were normalized with
      creatinine. Evidence was found to suggest an increase in psychostimulant use
      during periods of stress, with significant differences found from self-report
      data between the first week and midterms and from chemical data between these
      same two assessment periods as well as between the first week of classes and
      finals. Key predictors of lifetime non-prescriptive psychostimulant use included
      self-reported procrastination and poor time-management, use of other substances
      (especially nicotine/tobacco, alcohol, and cocaine), and students' perception of
      non-prescriptive psychostimulant use as normative on campus. The findings shed
      further light on psychostimulant use patterns among college students,
      particularly as a function of stress; the study also highlights the benefit of
      utilizing an interdisciplinary approach that uses both subjective and objective
      empirical data. The results have implications for prevention/intervention
      programs on college campuses designed to reduce stress and facilitate healthier
      coping. 

PMID- 24561017
TI  - Characteristics of transgender individuals entering substance abuse treatment.
AB  - Little is known about the needs or characteristics of transgender individuals in
      substance abuse treatment settings. Transgender (n=199) and non-transgender
      (cisgender, n=13,440) individuals were compared on psychosocial factors related
      to treatment, health risk behaviors, medical and mental health status and
      utilization, and substance use behaviors within a database that documented
      individuals entering substance abuse treatment in San Francisco, CA from 2007 to
      2009 using logistic and linear regression analyses (run separately by identified
      gender). Transgender men (assigned birth sex of female) differed from cisgender
      men across many psychosocial factors, including having more recent employment,
      less legal system involvement, greater incidence of living with a substance
      abuser, and greater family conflict, while transgender women (assigned birth sex
      of male) were less likely to have minor children than cisgender women.
      Transgender women reported greater needle use, and HIV testing rates were greater
      among transgender women. Transgender men and women reported higher rates of
      physical health problems, mental health diagnoses, and psychiatric medications,
      but there were no differences in service utilization. There were no differences
      in substance use behaviors except that transgender women were more likely to
      endorse primary methamphetamine use. Transgender individuals evidence unique
      strengths and challenges that could inform targeted services in substance abuse
      treatment. 

PMID- 24561019
TI  - Endocarditis due to Neisseria mucosa: case report and review of 21 cases: a rare
      and severe cause of endocarditis.

PMID- 24561018
TI  - Clinical characteristics and outcomes of hematogenous vertebral osteomyelitis
      caused by gram-negative bacteria.
AB  - OBJECTIVE: To evaluate the clinical characteristics and outcomes of patients with
      hematogenous vertebral osteomyelitis (HVO) caused by gram-negative bacteria
      (GNB). METHODS: We conducted a retrospective chart review of adult patients with
      HVO from three tertiary-care hospitals over a 7-year period. RESULTS: Of the 313
      microbiologically diagnosed HVO cases, GNB was responsible for 65 (20.8%) cases.
      Compared with patients with MSSA HVO, patients with GNB HVO were more likely to
      be female (P = 0.03) and have diabetes (P = 0.03), but less likely to have
      epidural abscess (P = 0.02) and paravertebral abscess (P = 0.003). Clinical
      outcomes were similar between the GNB and MSSA groups, including in-hospital
      mortality (4.6% vs. 7.8%; P = 0.53), recurrence (9.7% vs. 4.3%; P = 0.20), and
      sequelae (31.7% vs. 32.2%; P = 0.95). Among GNB-infected patients, recurrence
      rates differed according to the total duration of antibiotic treatment: 40.0% (4
      6 weeks), 33.3% (6-8 weeks), and 2.1% (>= 8 weeks) (P = 0.002). CONCLUSIONS: GNB
      HVO was responsible for 20.8% of adult cases of HVO. Despite some differences in
      clinical and radiological presentation, clinical outcomes were similar between
      GNB and MSSA HVO. Antibiotic therapy for >= 8 weeks may benefit patients with GNB
      HVO.

PMID- 24561020
TI  - SAPHO syndrome treatment with intravenous pamidronate. Retrospective study of 22
      patients.

PMID- 24561021
TI  - Systemic diseases and biotherapies: understanding, evaluating, and preventing the
      risk of hepatitis B reactivation.
AB  - Hepatitis B virus (HBV) reactivation can occur in chronic carriers of the HBV
      surface antigen (HBsAg) and constitutes a well-known complication of
      immunosuppressive therapy. HBV reactivation has also been reported after contact
      with the HBV. The increasing use of biological agents (TNFalpha antagonists,
      rituximab, abatacept, and tocilizumab) to treat systemic diseases has resulted in
      numerous publications about the risk of HBV reactivation. The relevant scientific
      societies have issued recommendations designed to prevent HBV reactivation. The
      main measures consist of screening for markers indicating chronic HBV infection
      (HBsAg) or HBV infection in the distant past (antibodies to the HBV core antigen)
      before initiating biological therapies, vaccinating marker-negative patients, and
      considering close follow-up or antiviral treatment before immunosuppressive
      treatment initiation or in the event of HBV reactivation. Here, we discuss the
      pathophysiological mechanisms underlying HBV reactivation during biological
      treatments, most notably in patients with occult HBV infection or markers for
      remote HBV infection, whose hepatocyte nuclei may contain a resistance form of
      HBV DNA known as covalently closed circular DNA (cccDNA). Assessment of the risk
      of reactivation relies on the HBV status, drugs used, and data from the
      literature. Finally, we discuss the various recommendations and modalities for
      HBV vaccination, preemptive treatment, and patient management, according to the
      level of risk and to the circumstances in which reactivation occurs. 

PMID- 24561022
TI  - Compression of the posterior interosseous nerve by a deep lipoma.

PMID- 24561023
TI  - Gene expression profile predicting the response to anti-TNF treatment in patients
      with rheumatoid arthritis; analysis of GEO datasets.
AB  - OBJECTIVES: Anti-tumor necrosis factor (TNF) therapy is the treatment of choice
      for rheumatoid arthritis (RA) patients in whom standard disease-modifying anti
      rheumatic drugs are ineffective. However, a substantial proportion of RA patients
      treated with anti-TNF agents do not show a significant clinical response.
      Therefore, biomarkers predicting response to anti-TNF agents are needed.
      Recently, gene expression profiling has been applied in research for developing
      such biomarkers. METHODS: We compared gene expression profiles reported by
      previous studies dealing with the responsiveness of anti-TNF therapy in RA
      patients and attempted to identify differentially expressed genes (DEGs) that
      discriminated between responders and non-responders to anti-TNF therapy. We used
      microarray datasets available at the National Center for Biotechnology
      Information (NCBI) Gene Expression Omnibus (GEO). RESULTS: This analysis included
      6 studies and 5 sets of microarray data that used peripheral blood samples for
      identification of DEGs predicting response to anti-TNF therapy. We found little
      overlap in the DEGs that were highly ranked in each study. Three DEGs including
      IL2RB, SH2D2A and G0S2 appeared in more than 1 study. In addition, a meta
      analysis designed to increase statistical power found one DEG, G0S2 by the
      Fisher's method. CONCLUSION: Our finding suggests the possibility that G0S2 plays
      as a biomarker to predict response to anti-TNF therapy in patients with
      rheumatoid arthritis. Further investigations based on larger studies are
      therefore needed to confirm the significance of G0S2 in predicting response to
      anti-TNF therapy.

PMID- 24561024
TI  - Paradoxical psoriatic arthritis in a patient with rheumatoid arthritis treated by
      TNFalpha blocker.

PMID- 24561026
TI  - Isolation of a pure octadecasaccharide with antithrombin activity from an ultra
      low-molecular-weight heparin.
AB  - Heparin and low-molecular-weight heparins (LMWHs) are anticoagulant drugs that
      mainly inhibit the coagulation cascade by indirectly interacting with factor Xa
      and factor IIa (thrombin). Inhibition of factor Xa by antithrombin (AT) requires
      the activation of AT by specific pentasaccharide sequences containing 3-O
      sulfated glucosamine. Activated AT also inhibits thrombin by forming a stable
      ternary complex of AT, thrombin, and a polysaccharide (requires at least an 18
      mer/octadeca-mer polysaccharide). The full structure of any naturally occurring
      octadecasaccharide sequence has yet to be determined. In the context of the
      development of LMWH biosimilars, structural data on such important biological
      mediators could be helpful for better understanding and regulatory handling of
      these drugs. Here we present the isolation and identification of an
      octadecasaccharide with very high anti-factor Xa activity (~3 times higher than
      USP [U.S. Pharmacopeia] heparin). The octadecasaccharide was purified using five
      sequential chromatographic methods with orthogonal specificity, including gel
      permeation, AT affinity, strong anion exchange, and ion-pair chromatography. The
      structure of the octadecasaccharide was determined by controlled enzymatic
      sequencing and nuclear magnetic resonance (NMR). The isolated octadecasaccharide
      contained three consecutive AT-binding sites and was tested in coagulation assays
      to determine its biological activity. The isolation of this octadecasaccharide
      provides new insights into the modulation of thrombin activity. 

PMID- 24561025
TI  - Enhanced assay of endothelial exocytosis using extracellular matrix components.
AB  - Vascular inflammation plays a key role in the pathogenesis of atherosclerosis.
      The first step in vascular inflammation is endothelial exocytosis, in which
      endothelial granules fuse with the plasma membrane, releasing prothrombotic and
      proinflammatory messenger molecules. The development of cell culture models to
      study endothelial exocytosis has been challenging because the factors that
      modulate exocytosis in vitro are not well understood. Here we report a method for
      studying endothelial exocytosis that optimizes extracellular matrix components,
      cell density, and duration of culture. Human umbilical vein endothelial cells
      plated on collagen I-coated plates and cultured in the confluent state for 7-12
      days in low-serum medium showed robust secretion of von Willebrand factor when
      stimulated with various agonists. This exocytosis assay is rapid and applicable
      to high-throughput screening.

PMID- 24561027
TI  - Unconventional surface plasmon resonance signals reveal quantitative inhibition
      of transcriptional repressor EthR by synthetic ligands.
AB  - EthR is a mycobacterial repressor that limits the bioactivation of ethionamide, a
      commonly used anti-tuberculosis second-line drug. Several efforts have been
      deployed to identify EthR inhibitors abolishing the DNA-binding activity of the
      repressor. This led to the demonstration that stimulating the bioactivation of
      Eth through EthR inhibition could be an alternative way to fight Mycobacterium
      tuberculosis. We propose a new surface plasmon resonance (SPR) methodology to
      study the affinity between inhibitors and EthR. Interestingly, the binding
      between inhibitors and immobilized EthR produced a dose-dependent negative SPR
      signal. We demonstrate that this signal reveals the affinity of small molecules
      for the repressor. The affinity constants (K(D)) correlate with their capacity to
      inhibit the binding of EthR to DNA. We hypothesize that conformational changes in
      EthR during ligand interaction could be responsible for this SPR signal.
      Practically, this unconventional result opens perspectives onto the development
      of an SPR assay that would at the same time reveal structural changes in the
      target upon binding with an inhibitor and the binding constant of this
      interaction.

PMID- 24561029
TI  - Standardized measurement of the Modified Early Warning Score results in enhanced
      implementation of a Rapid Response System: a quasi-experimental study.
AB  - PURPOSE: To study the effect of protocolized measurement (three times daily) of
      the Modified Early Warning Score (MEWS) versus measurement on indication on the
      degree of implementation of the Rapid Response System (RRS). METHODS: A quasi
      experimental study was conducted in a University Hospital in Amsterdam between
      September and November 2011. Patients who were admitted for at least one
      overnight stay were included. Wards were randomized to measure the MEWS three
      times daily ("protocolized") versus measuring the MEWS "when clinically
      indicated" in the control group. At the end of each month, for an entire seven
      day week, all vital signs recorded for patients were registered. The outcomes
      were categorized into process measures including the degree of implementation and
      compliance to set monitoring standards and secondly, outcomes such as the degree
      of delay in physician notification and Rapid Response Team (RRT) activation in
      patients with raised MEWS (MEWS>=3). RESULTS: MEWS calculations from vital signs
      occurred in 70% (2513/3585) on the protocolized wards versus 2% (65/3013) in the
      control group. Compliance with the protocolized regime was presents in 68%
      (819/1205), compliance in the control group was present in 4% (47/1232) of the
      measurements. There were 90 calls to primary physicians on the protocolized and 9
      calls on the control wards. Additionally on protocolized wards, there were twice
      as much RRT calls per admission. CONCLUSIONS: Vital signs and MEWS determination
      three times daily, results in better detection of physiological abnormalities and
      more reliable activations of the RRT.

PMID- 24561030
TI  - Value analysis of continuous EEG in patients during therapeutic hypothermia after
      cardiac arrest.
AB  - INTRODUCTION: Therapeutic hypothermia (TH) is standard of care after ventricular
      fibrillation cardiac arrest (CA). Continuous EEG monitoring (cEEG) is
      increasingly used during TH. Analysis regarding value of cEEG utilization in this
      population in the context of cost and outcome has not been performed. We compared
      outcome and EEG charges in CA patients with selective versus routine cEEG.
      METHODS: A protocol for TH after CA without routine cEEG was implemented in
      December 2005, comprising our TH-pre-cEEG cohort. In November 2009, this protocol
      was changed to include cEEG in all CA-TH patients, comprising our TH-cEEG cohort.
      Clinical outcome using the Cerebral Performance Category (CPC) at discharge and
      estimated EEG charges were calculated retrospectively for both cohorts, based on
      National Charge Data 50th percentile charges expressed in USD per the CMS 2010
      Standard Analytical File as reported in Code Correct by MedAssets, Inc. RESULTS:
      Our TH-pre-cEEG cohort comprised 91 patients, our TH-cEEG cohort 62. In the TH
      pre-cEEG cohort, 19 patients (21%) had rEEGs, 4 (4%) underwent cEEG. The mean
      estimated EEG charges for the TH-pre-cEEG cohort was $1571.59/patient, and TH
      cEEG cohort was $4214.93/patient (p<0.0001). Two patients (2.1%) in the TH-pre
      cEEG cohort had seizures, compared to five (8.1%) in the TH-cEEG cohort
      (p=0.088). There was no difference in mortality or clinical outcome in these
      cohorts. CONCLUSIONS: Routine use of cEEG during TH after CA improved seizure
      detection, but not outcomes. There was a three-fold increase in EEG estimated
      charges with routine use of cEEG.

PMID- 24561028
TI  - Anti-rheumatoid arthritic activity of flavonoids from Daphne genkwa.
AB  - The aim of the study was to investigate the anti-rheumatoid arthritic activity of
      four flavonoids from Daphne genkwa (FFD) in vivo and in vitro. Flavonoids of D.
      genkwa were extracted by refluxing with ethanol and purified by polyamide resin.
      An in vivo carrageenan-induced paw edema model, tampon-granuloma model and
      Freund's complete adjuvant (FCA)-induced arthritis mouse model were used to
      evaluate the anti-rheumatoid arthritic activities of FFD. Moreover, nitric oxide
      (NO) release and neutral red uptake (NRU) in lipopolysaccharide (LPS)-induced
      murine macrophage RAW264.7 cells were used to evaluate the anti-inflammatory
      effect in vitro. In addition, antioxidant effect of FFD was determined using the
      2,2-diphenyl-1-picrylhydrazyl (DPPH) method. A high dose of FFD significantly
      reduced the degree of acute inflammatory paw edema in mice as a response to
      carrageenan administration (p<0.01). FFD displayed a dose-dependent inhibition of
      granuloma formation in mice (p<0.05). FFD also inhibited chronic inflammation in
      adjuvant-induced arthritis rats when administered orally at the dose of
      50mg/kg/day (p<0.001). In addition, FFD suppressed the production of NO and
      exhibited immunoregulatory function in LPS-activated RAW264.7 cells in a dose
      related manner. Simultaneously, FFD revealed conspicuous antioxidant activity
      with IC50 values of 18.20MUg/ml. FFD possesses significant anti-inflammatory and
      antioxidant activity, which could be a potential therapeutic agent for chronic
      inflammatory disorders such as rheumatoid arthritis. 

PMID- 24561031
TI  - Improving oncologic outcomes for women with endometrial cancer: realigning our
      sights.
AB  - This review will examine existing results on the postoperative treatment of women
      with high-risk and advanced stage endometrial cancer. Preliminary data suggests
      that response to treatment is highly dependent on both grade and stage. It is
      hoped that this discussion will highlight deficiencies in our collective
      knowledge base to be addressed in future clinical trials for the benefit of women
      with endometrial cancer. 

PMID- 24561032
TI  - Assessing the efficacy of targeting the phosphatidylinositol 3-kinase/AKT/mTOR
      signaling pathway in endometrial cancer.
AB  - OBJECTIVE: Alterations in the PI3K pathway are prevalent in endometrial cancer
      due to PIK3CA mutation and loss of PTEN. We investigated the anti-tumor activity
      of the PI3K inhibitor NVP BKM-120 (BKM) as a single agent and in combination with
      standard cytotoxic chemotherapy in a human primary endometrial xenograft model.
      METHODS: NOD/SCID mice bearing xenografts of primary human tumors with and
      without PIK3CA gene mutations were divided into two and four arm cohorts with
      equivalent tumor volumes. BKM was administered alone and in combination with
      paclitaxel and carboplatin (P/C) and endometrial xenograft tumor volumes were
      assessed. Tumors from the BKM, P/C, P/C+BKM and vehicle treated mice were
      processed for determination of PI3K/AKT/mTOR pathway activation. RESULTS: In both
      single agent experiments, BKM resulted in significant tumor growth suppression
      starting at days 5-10 compared to the linear growth observed in vehicle treated
      tumors (p<0.04 in all experiments). Tumor resurgence manifested between days 14
      and 25 (p<0.03). When BKM was combined with P/C, this resistance pattern failed
      to develop in three separate xenograft lines (p<0.05). Synergistic tumor growth
      suppression (p<0.05) of only one xenograft tumor with no detected PIK3CA mutation
      was observed. Acute treatment with BKM led to a decrease in pAKT levels.
      CONCLUSION: Independent of PIK3CA gene mutation, BKM mediated inhibition of the
      PI3K/AKT/mTOR pathway in endometrial tumors precludes tumor growth in a primary
      xenograft model. While a pattern of resistance emerges, this effect appears to be
      mitigated by the addition of conventional cytotoxic chemotherapy.

PMID- 24561033
TI  - Predictors of multiple sexual partners from adolescence through young adulthood.
AB  - PURPOSE: To examine time-varying associations between predictors of recent
      multiple sexual partners from middle adolescence through young adulthood.
      METHODS: We examined whether the odds of multiple partners in the past year were
      differentially predicted by substance use and depression over time, using data
      from a nationally representative longitudinal study (N = 11,963, 52.2% female,
      18.3% African-American, 11.9% Hispanic, 3.5% Asian, 2.6% other race, M age at
      Wave I = 16.1 years, SD = 1.8). Data were analyzed using the time-varying effect
      model, which estimates associations between predictors and an outcome as a
      function of near-continuous time. RESULTS: The proportion of participants having
      multiple partners increased over time, leveling off at around 30% after age 20.
      Significant positive associations between substance use and multiple partners
      were strongest early in adolescence and decreased sharply by around age 18. The
      significant positive association between depression and sexual behavior weakened
      with age, remaining significant in young adulthood for women but not men.
      CONCLUSIONS: These findings suggest that factors associated with having multiple
      recent sexual partners change from middle adolescence through young adulthood.
      The time-varying effect model can be used to identify risk factors that are
      especially salient at different ages, thus identifying which age periods may hold
      the greatest promise for intervention.

PMID- 24561034
TI  - Alpha power increases in right parietal cortex reflects focused internal
      attention.
AB  - This study investigated the functional significance of EEG alpha power increases,
      a finding that is consistently observed in various memory tasks and specifically
      during divergent thinking. It was previously shown that alpha power is increased
      when tasks are performed in mind-e.g., when bottom-up processing is prevented.
      This study aimed to examine the effect of task-immanent differences in bottom-up
      processing demands by comparing two divergent thinking tasks, one intrinsically
      relying on bottom-up processing (sensory-intake task) and one that is not
      (sensory-independence task). In both tasks, stimuli were masked in half of the
      trials to establish conditions of higher and lower internal processing demands.
      In line with the hypotheses, internal processing affected performance and led to
      increases in alpha power only in the sensory-intake task, whereas the sensory
      independence task showed high levels of task-related alpha power in both
      conditions. Interestingly, conditions involving focused internal attention showed
      a clear lateralization with higher alpha power in parietal regions of the right
      hemisphere. Considering evidence from fMRI studies, right-parietal alpha power
      increases may correspond to a deactivation of the right temporoparietal junction,
      reflecting an inhibition of the ventral attention network. Inhibition of this
      region is thought to prevent reorienting to irrelevant stimulation during goal
      driven, top-down behavior, which may serve the executive function of task
      shielding during demanding cognitive tasks such as idea generation and mental
      imagery. 

PMID- 24561035
TI  - Enhanced distraction by magnocellular salience signals in schizophrenia.
AB  - Research on schizophrenia has provided evidence of both impaired attentional
      control and dysfunctional magnocellular sensory processing. The present study
      tested the hypothesis that these impairments may be related, such that people
      with schizophrenia would be differentially distracted by stimuli that strongly
      activate the magnocellular pathway. To accomplish this, we used a visual
      attention paradigm from the basic cognitive neuroscience literature designed to
      assess the capture of attention by salient but irrelevant stimuli. Participants
      searched for a target shape in an array of non-target shapes. On some trials, a
      salient distractor was presented that either selectively activated the
      parvocellular system (parvo-biased distractors) or activated both the
      magnocellular and parvocellular systems (magno+parvo distractors). For both
      manual reaction times and eye movement measures, the magno+parvo distractors
      captured attention more strongly than the parvo-biased distractors in people with
      schizophrenia, but the opposite pattern was observed in matched healthy control
      participants. These results indicate that attentional control deficits in
      schizophrenia may arise, at least in part, by means of an interaction with
      magnocellular sensory dysfunction.

PMID- 24561037
TI  - En bloc resections for primary spinal tumors in 20 years of experience:
      effectiveness and safety.
AB  - BACKGROUND CONTEXT: Many studies have demonstrated that en bloc surgical
      resection of primary spinal tumors with adequate margins results in improved
      local disease control and survival compared with intralesional excision.
      Nevertheless, the use of this procedure is under debate because most of the
      current evidence is provided by small and heterogeneous series of cases. PURPOSE:
      To validate the application of en bloc resection for the treatment of aggressive
      benign and primary malignant spinal tumors. STUDY DESIGN: This is a prospective
      cohort study. PATIENT SAMPLE: From August 1990 to March 2010, 103 consecutive
      patients affected by primary spinal tumors were enrolled in the study. All
      patients were submitted to the same clinical and imaging workup. OUTCOME
      MEASURES: Analysis of local recurrence (LR) and tumor-related mortality,
      reliability of preoperative surgical planning, and morbidity and mortality. In
      addition, the effects of possible predictors of these events were studied.
      METHODS: The parameters for the effectiveness and safety of en bloc resections
      performed on primary spinal tumors were considered as primary end points of this
      study, and two research questions were formulated. The analysis of the procedure
      effectiveness considered the identification of possible predictors of LR and
      tumor-related mortality. Information about safety is collected so as to clarify
      the possibility to respect the preoperative planning and to identify possible
      predictors of morbidity and mortality. Data from clinical and imaging examination
      were collected in a database and were used to answer the proposed research
      questions. RESULTS: All patients were followed for a minimum of 24 months or
      until death. At the final assessment, 69 patients resulted with no evidence of
      disease with a mean follow-up of 100 months. Among the 103 patients, tumor
      recurred in 22 cases with a mean follow-up period of 39 months after surgery. A
      Cox regression multivariate analysis shows that marginal and intralesional
      resections are independent predictors of LR (hazard ratio [HR] 9.45, 95%
      confidence interval [CI] 1.06-84.47 and HR 38.62, 95% CI 4.67-319.21,
      respectively, compared with wide resection) and tumor-related mortality (in
      particular, HR 17.10, 95% CI 3.80-77.04 for intralesional resection compared with
      the wide one). The same analysis demonstrates that en bloc resection performed in
      recurrent cases or patients previously submitted to open biopsy (nonintact cases)
      have a LR risk higher than intact cases (HR 3.45, 95% CI 1.38-8.63). The success
      rate of en bloc resections in achieving adequate margins is 82.4%, and Weinstein
      Boriani-Biagini surgical staging can also predict the margins in a high
      percentage of cases (75.7%). Complications occurred in 41.7% of patients with a
      higher rate observed in the nonintact group and for surgery with a double
      approach or multisegmental resections. The mortality rate related to surgery
      complications was 1.9%, whereas tumor-related mortality was 15.5%. CONCLUSIONS:
      Statistical analysis of the long-term results referred to 103 patients affected
      by aggressive benign and malignant primary spine tumors indicates that an en bloc
      resection is associated with a high rate of complications. Nevertheless, it
      decreases the risk of LR and tumor-related mortality. En bloc resection is a
      highly demanding procedure but can be performed to an acceptable degree of
      safety.

PMID- 24561036
TI  - Diffusion tensor imaging predicts functional impairment in mild-to-moderate
      cervical spondylotic myelopathy.
AB  - BACKGROUND CONTEXT: Magnetic resonance imaging (MRI) is the standard imaging
      modality for the assessment of cervical spinal cord; however, MRI assessment of
      the spinal cord in cervical spondylotic myelopathy patients has not demonstrated
      a consistent association with neurologic function or outcome after surgical or
      medical intervention. Thus, there is a need for sensitive imaging biomarkers that
      can predict functional impairment in patients with advanced cervical spondylosis.
      PURPOSE: To implement diffusion tensor imaging (DTI) as an imaging biomarker for
      microstructural integrity and functional impairment in patients with cervical
      spondylosis. STUDY DESIGN: Nonrandomized, single institution study. PATIENT
      SAMPLE: Forty-eight cervical spondylosis patients with or without spinal cord
      signal change underwent DTI of the spinal cord along with functional assessment.
      OUTCOME MEASURES: Functional measures of neurologic function via modified
      Japanese Orthopedic Association (mJOA) score. METHODS: A zoomed-echoplanar
      imaging technique and two-dimensional spatially selective radiofrequency
      excitation pulse were used for DTI measurement. Fractional anisotropy (FA), mean
      diffusivity (MD), radial and axial diffusion (AD) coefficient, AD anisotropy,
      psi, defined as AD-MD, and the standard deviation (SD) of primary eigenvector
      orientation were evaluated at the site of compression. RESULTS: Results suggest
      average FA, transverse apparent diffusion coefficient, psi, and SD of primary
      eigenvector orientation at the spinal level of highest compression were linearly
      correlated with mJOA score. Receiver-operator characteristic analysis suggested
      FA and psi could identify stenosis patients with mild-to-moderate symptoms with a
      relatively high sensitivity and specificity. CONCLUSIONS: The results of this
      study support the potential use of DTI as a biomarker for predicting functional
      impairment in patients with cervical spondylosis.

PMID- 24561038
TI  - Calcineurin regulates coordinated outgrowth of zebrafish regenerating fins.
AB  - Vertebrates develop organs and appendages in a proportionally coordinated manner,
      and animals that regenerate them do so to the same dimensions as the original
      structures. Coordinated proportional growth involves controlled regulation
      between allometric and isometric growth programs, but it is unclear what executes
      this control. We show that calcineurin inhibition results in continued allometric
      outgrowth of regenerating fins beyond their original dimensions. Calcineurin
      inhibition also maintains allometric growth of juvenile fins and induces it in
      adult fins. Furthermore, calcineurin activity is low when the regeneration rate
      is highest, and its activity increases as the rate decreases. Growth measurements
      and morphometric analysis of proximodistal asymmetry indicate that calcineurin
      inhibition shifts fin regeneration from a distal growth program to a proximal
      program. This shift is associated with the promotion of retinoic acid signaling.
      Thus, we identified a calcineurin-mediated mechanism that operates as a molecular
      switch between position-associated isometric and allometric growth programs. 

PMID- 24561040
TI  - Experimental research on the relationship between fit accuracy and fracture
      resistance of zirconia abutments.
AB  - OBJECTIVES: The purpose of the study was to investigate the correlation between
      fit accuracy and fracture resistance of zirconia abutments, as well as its
      feasibility for clinical applications. METHODS: Twenty self-made zirconia
      abutments were tested with 30 Osstem GSII implants. First, 10 Osstem GSII
      implants were cut into two parts along the long axis and assembled with the
      zirconia abutments. The microgaps between the implants and the zirconia abutments
      were measured under a scanning electron microscope. Second, the zirconia
      abutments were assembled with 20 un-cut implants and photographed before and
      after being fixed with a central screw of 30-Ncm torque. The dental films were
      measured by Digora for Windows 2.6 software. Then the fracture resistance of
      zirconia abutments was measured using the universal testing machine at 90 degrees
      . All results were analyzed using SPSS13.0 software. RESULTS: The average
      internal-hexagon microgaps between the implants and zirconia abutments were
      19.38+/-1.34MUm. The average Morse taper microgap in the implant-abutment
      interface was 17.55+/-1.68MUm. The dental film showed that the Morse taper gap in
      the implant-abutment interface disappeared after being fixed with a central screw
      of 30-Ncm torque, and the average moving distance of the zirconia abutments to
      the implants was 0.19+/-0.02mm. The average fracture resistance of zirconia
      abutments was 282.93+/-17.28N. The internal-hexagon microgap between the implants
      and zirconia abutments was negatively related to the fracture resistance of the
      abutments (r1=-0.97, p<0.01). The Morse taper microgap in the implant-abutment
      interface was negatively related to the fracture resistance of the abutments (r2=
      0.84, p<0.01). CONCLUSIONS: The microgap between implant and abutment was
      negatively related to the fracture resistance of the abutment, while the internal
      hexagon microgap has better correlation than the Morse taper microgap. The
      closure of microgap is helpful to improve the fracture resistance of zirconia
      abutments. The fracture resistance of zirconia abutments can satisfy the clinical
      application.

PMID- 24561039
TI  - Rab11 endosomes contribute to mitotic spindle organization and orientation.
AB  - During interphase, Rab11-GTPase-containing endosomes recycle endocytic cargo.
      However, little is known about Rab11 endosomes in mitosis. Here, we show that
      Rab11 localizes to the mitotic spindle and regulates dynein-dependent endosome
      localization at poles. We found that mitotic recycling endosomes bind gamma-TuRC
      components and associate with tubulin in vitro. Rab11 depletion or dominant
      negative Rab11 expression disrupts astral microtubules, delays mitosis, and
      redistributes spindle pole proteins. Reciprocally, constitutively active Rab11
      increases astral microtubules, restores gamma-tubulin spindle pole localization,
      and generates robust spindles. This suggests a role for Rab11 activity in spindle
      pole maturation during mitosis. Rab11 depletion causes misorientation of the
      mitotic spindle and the plane of cell division. These findings suggest a
      molecular mechanism for the organization of astral microtubules and the mitotic
      spindle through Rab11-dependent control of spindle pole assembly and function. We
      propose that Rab11 and its associated endosomes cocontribute to these processes
      through retrograde transport to poles by dynein. 

PMID- 24561041
TI  - Marginal adaptation of class II cavities restored with bulk-fill composites.
AB  - OBJECTIVES: To determine the marginal adaptation of bulk-fill composites in class
      II MO cavities. METHODS: Standardized class II MO cavities with bevelled enamel
      margins were prepared in 40 extracted human molars. The teeth were randomly
      assigned to one of the five experimental groups (n=8). The teeth were restored
      with two horizontal increments of composite (4mm and 2mm thickness). The
      experimental groups were (1st/2nd increment): Gr. A - Venus Bulk-Fill/Venus
      Diamond; Gr. B - Tetric EvoCeram BulkFill/Tetric EvoCeram; Gr. C - Surefil
      SDR/Ceram-X; Gr. D - SonicFill; Gr. E - Ceram-X/Ceram-X (control). After
      finishing procedures, impressions were made using a polyvinyl siloxane and epoxy
      resin replicas were obtained. Thermo-mechanical stressing was carried out 24h
      after the restorative procedure. All specimens were submitted to 240,000 occlusal
      loading and simultaneous 600 thermal cycles in water at 5 degrees C and 50
      degrees C. After loading, a new set of epoxy resin replicas was obtained.
      Scanning electron microscopy was carried out at 200* magnification. Results for
      the marginal adaptation were expressed as percentages of continuity relative to
      the exposed interface and analyzed by ANOVA and Duncan post hoc test (p<0.05).
      RESULTS: In enamel, no significant differences were detected before and after
      thermo-mechanical loading between groups. In dentine, the worst results were
      observed in Gr. A CONCLUSION: By applying simple layering techniques, bulk-fill
      materials do not allow better marginal adaptation than a standard composite.
      CLINICAL SIGNIFICANCE: A new class of resin-base composite (bulk-fill) was
      recently launched on the market. The bulk-fill composites exhibited adequate
      marginal adaptation and similar to the results of the standard composite.

PMID- 24561042
TI  - Effect of chlorhexidine and ethanol-wet bonding with a hydrophobic adhesive to
      intraradicular dentine.
AB  - PURPOSE: To evaluate the effect of adjunctive application of ethanol-wet bonding
      and chlorhexidine (CHX) with a hydrophobic adhesive on bond durability of fibre
      posts to intraradicular dentine. METHODS: Ninety-six extracted human teeth with a
      single root and root canal were prepared for post placement after endodontic
      treatment. The teeth were randomly divided into four groups (n=24) after etching
      and rinsing for rewetting: Group 1: water-wet bonding, Group 2: water-wet bonding
      with CHX, Group 3: ethanol-wet bonding and Group 4: ethanol-wet bonding with CHX.
      Teeth in Groups 1 and 2 were treated with either distilled water or distilled
      water with 2% CHX for 60 s; while teeth in Groups 3 and 4 were treated with
      either 100% ethanol or 100% ethanol with 2% CHX. Two coats of primer, followed by
      neat resin were applied and light-cured for 40 s. Fibre posts were luted to
      bonded root dentine using dual-cure resin cement. Bonded roots were subjected to
      push-out bond strength testing and interfacial nanoleakage evaluation after 24 h,
      6 and 12 months of storage. Data were analyzed using 3-way ANOVA (rewetting
      solutions, time and post space regions) and SNK tests. RESULTS: Groups 3 and 4
      showed significantly (p<0.05) higher bond strengths and lower nanoleakage than
      Groups 1 and 2 after 12 months of ageing. Addition of 2% chlorhexidine to ethanol
      wet bonding with a hydrophobic adhesive did not further improve the bonding of a
      fibre post to intraradicular dentine, when compared to ethanol-wet bonding alone
      after 12 months of ageing. CLINICAL SIGNIFICANCE: Ethanol-wet bonding with a
      hydrophobic adhesive alone could improve the bond durability of fibre post to
      intraradicular dentine and therefore would increase the success rate of post and
      core restorations of endodontically treated teeth.

PMID- 24561043
TI  - The dual PI3K/mTOR inhibitor NVP-BEZ235 prevents epithelial-mesenchymal
      transition induced by hypoxia and TGF-beta1.
AB  - Epithelial-mesenchymal transition (EMT) is regarded as the most important
      mechanism behind the initiation of cancer metastasis. Though there has been great
      interest in developing therapies aimed at impairing the process of EMT, only few
      molecules have been identified to orchestrate it so far. Here we report that the
      dual PI3K/mTOR inhibitor NVP-BEZ235 is capable of preventing human ovarian cancer
      cell line SKOV-3 and prostatic cancer cell line PC-3 from hypoxia- and TGF-beta1
      induced EMT. The addition of NVP-BEZ235 reverses the EMT-like morphologic
      changes, down-regulation of E-cadherin, and enhancement of cell migration induced
      by 1% O2 partially through interfering with the expression and transcriptional
      activity of Hif-1alpha via PI3K/mTOR pathway. In addition, NVP-BEZ235 inhibits
      TGF-beta1-induced phosphorylation of Smad2/3 and Akt/GSK-3beta, reduces the
      expression of Snail both in transcriptional and post-translational level, and
      consequently prevents the repression of E-cadherin expression as well as the
      increase of cell motility caused by TGF-beta1. Moreover, in nude mice bearing
      SKOV-3 ovarian cancer xenografts, NVP-BEZ235 significantly increases the mRNA
      level of E-cadherin. Taken together, our study demonstrates, for the first time,
      NVP-BEZ235 can prevent microenvironment and growth factor induced EMT, which
      suggests this agent as a potential candidate for cancer metastasis treatment. 

PMID- 24561044
TI  - Effects of acute and chronic administration of venlafaxine and desipramine on
      extracellular monoamine levels in the mouse prefrontal cortex and striatum.
AB  - Prefrontal catecholamine neurotransmission plays a key role in the therapeutic
      actions of drugs for attention-deficit/hyperactivity disorder (ADHD). We have
      recently shown that serotonin/noradrenaline reuptake inhibitors and the
      noradrenaline reuptake inhibitor desipramine attenuated horizontal hyperactivity
      in spontaneously hypertensive rats, an animal model of ADHD, and that these drugs
      are potential pharmacotherapeutics for ADHD. In this study, we used in vivo
      microdialysis to study the effects of acute and chronic (once daily for 3 weeks)
      administration of the serotonin/noradrenaline reuptake inhibitor venlafaxine and
      the noradrenaline reuptake inhibitor desipramine on noradrenaline, dopamine, and
      serotonin levels, and the expression of the neuronal activity marker c-Fos in the
      mouse prefrontal cortex and striatum. Both acute and chronic venlafaxine
      administration increased prefrontal noradrenaline, dopamine, and serotonin levels
      and striatal noradrenaline and serotonin levels. Both acute and chronic
      desipramine administration increased prefrontal noradrenaline and dopamine levels
      and striatal noradrenaline levels, with chronic administration yielding stronger
      increase. Chronic desipramine did not affect striatal dopamine and serotonin
      levels. Both acute and chronic venlafaxine administration increased the
      expression of c-Fos in the prefrontal cortex, whereas chronic, but not acute,
      desipramine administration increased the expression of c-Fos in the prefrontal
      cortex. Both acute and chronic venlafaxine administration increased the striatal
      c-Fos expression to some degree, whereas desipramine administration did not.
      These results suggest that acute and chronic venlafaxine and chronic desipramine
      administration maximally activate the prefrontal adrenergic and dopaminergic
      systems without affecting striatal dopaminergic systems in mice. 

PMID- 24561045
TI  - The effects of different doses of silibinin in combination with methotrexate on
      testicular tissue of mice.
AB  - Methotrexate (MTX) is widely used chemotherapeutic agent with different side
      effects including germ cells toxicities. Silibinin is one of the structural
      isomers of silymarin, with different phytotherapeutic applications, and its
      possible protective effects against MTX induced germ cells damage were
      investigated in this work. Twenty five male mice were divided into five groups
      (n=5) allocated as follows: Group 1 received buffer for five days given by single
      intraperitoneal (IP) injection per day; Group 2 in addition to buffer for five
      days, animals received at day five single dose of 20mg/kg of MTX IP. Groups (3,
      4, and 5) received respectively, (50, 100, or 150mg/kg body weight) of silibinin
      IP single daily dose for five days then at day five 20mg/kg of MTX IP.
      Microscopic examinations of sperms, histological examinations of testis and serum
      testosterone had been measured. Silibinin showed a significant decrease in the
      percent of dead/live sperm with significant changes in interstitial space and in
      the diameter of spermatide. The results indicate that silibinin can mitigate some
      of the toxic effects of MTX in testicular tissue. 

PMID- 24561046
TI  - Cannabinoid receptor type 1 activation by arachidonylcyclopropylamide in rat
      aortic rings causes vasorelaxation involving calcium-activated potassium channel
      subunit alpha-1 and calcium channel, voltage-dependent, L type, alpha 1C subunit.
AB  - Cannabinoids are key regulators of vascular tone, some of the mechanisms involved
      include the activation of cannabinoid receptor types 1 and 2 (CB); the transient
      receptor potential cation channel, subfamily V, member 1 (TRPV1); and non
      (CB(1))/non-CB2 receptors. Here, we used the potent, selective CB(1) agonist
      arachidonylcyclopropylamide (ACPA) to elucidate the mechanism underlying vascular
      tone regulation. Immunohistochemistry and confocal microscopy revealed that CB(1)
      was expressed in smooth muscle and endothelial cells in rat aorta. We performed
      isometric tension recordings in aortic rings that had been pre-contracted with
      phenylephrine. In these conditions, ACPA caused vasorelaxation in an endothelium
      independent manner. To confirm that the effect of ACPA was mediated by CB(1)
      receptor, we repeated the experiment after blocking these receptors with a
      selective antagonist, AM281. In these conditions, ACPA did not cause
      vasorelaxation. We explored the role of K(+) channels in the effect of ACPA by
      applying high-K(+) solution to induce contraction in aortic rings. In these
      conditions, the ACPA-induced vasorelaxation was about half that observed with
      phenylephrine-induced contraction. Thus, K(+) channels were involved in the ACPA
      effect. Furthermore, the vasorelaxation effect was similarly reduced when we
      specifically blocked calcium-activated potassium channel subunit alpha-1 (KCa1.1)
      (MaxiK; BKCa) prior to adding ACPA. Finally, ACPA-induced vasorelaxation was also
      diminished when we specifically blocked the calcium channel, voltage-dependent, L
      type, alpha 1C subunit (Ca(v)1.2). These results showed that ACPA activation of
      CB(1) in smooth muscle caused vasorelaxation of aortic rings through a mechanism
      involving the activation of K(Ca)1.1 and the inhibition of Ca(v)1.2.

PMID- 24561047
TI  - Evaluation of selective cannabinoid CB(1) and CB(2) receptor agonists in a mouse
      model of lipopolysaccharide-induced interstitial cystitis.
AB  - Interstitial cystitis is a debilitating bladder inflammation disorder. To date,
      the understanding of the causes of interstitial cystitis remains largely
      fragmentary and there is no effective treatment available. Recent experimental
      results have shown a functional role of the endocannabinoid system in urinary
      bladder. In this study, we evaluated the anti-inflammatory effect of selective
      cannabinoid CB1 and CB2 receptor agonists in a mouse model of interstitial
      cystitis. Bladder inflammation was induced in mice by lipopolysaccharide (LPS)
      and whole bladders were removed 24h later. LPS induced a significant increase of
      the contractile amplitude in spontaneous activity and a hypersensitivity to
      exogenous acetylcholine-induced contraction of whole-isolated bladder. Next, we
      evaluated the anti-inflammatory activity of cannabinoidergic compounds by
      pretreating mice with CB1 or CB2 selective agonist compounds, respectively ACEA
      and JWH015. Interestingly, JWH015, but not ACEA, antagonized LPS-induced bladder
      inflammation. Additionally, anti-inflammatory activity was studied by evaluation,
      leukocytes mucosa infiltration, myeloperoxidase activity, and mRNA expression of
      pro-inflammatory interleukin (IL-1alpha and IL-1beta), tumor necrosis factor
      alpha (TNF-alpha) and cannabinoid CB1 and CB2 receptors. JWH015 significantly
      decreased leukocytes infiltration in both submucosa and mucosa, as well as the
      myeloperoxydase activity, in LPS treated mice. JWH015 reduced mRNA expression of
      IL-1alpha, IL-1beta, and TNF-alpha. LPS treatment increased expression of bladder
      CB2 but not CB1 mRNA. Taken together, these findings strongly suggest that
      modulation of the cannabinoid CB2 receptors might be a promising therapeutic
      strategy for the treatment of bladder diseases and conditions characterized by
      inflammation, such as interstitial cystitis. 

PMID- 24561048
TI  - Synergistic efficacy of meropenem and rifampicin in a murine model of sepsis
      caused by multidrug-resistant Acinetobacter baumannii.
AB  - Multidrug-resistant Acinetobacter baumannii becomes an increasing challenge due
      to the overuse of antibiotics. Combination therapies are considered as effective
      options to overcome this matter. The present study was to investigate the
      synergistic activity of meropenem combined with other antibiotics in vitro and in
      vivo. Checkerboard assay and time-kill assay were performed to study the
      combination effects in vitro. For the animal model, a murine sepsis model
      injected with inoculums intraperitoneally was used. Susceptibility test showed
      that all the twelve strains in this study were resistant to most of the
      antibiotics except rifampicin. In combination, meropenem plus rifampicin
      exhibited synergistic activity against six of twelve strains. In the sepsis
      model, meropenem monotherapy had no therapeutic effect in this model while it can
      enhance the activity of rifampicin in both survival rate and bacterial clearance
      from blood. Moreover, combination therapy significantly reduced plasma IL-6
      levels compared with rifampicin monotherapy. Pharmacokinetic analysis of
      rifampicin was also performed in this study. These data above showed that there
      was synergistic activity between meropenem and rifampicin against multidrug
      resistant Acinetobacter baumannii both in vitro and for experimental model of
      sepsis. It suggested that combining meropenem with rifampicin may be appropriate
      in treating multidrug-resistant Acinetobacter baumannii infections. 

PMID- 24561050
TI  - 1,2,3,4-Tetrahydroisoquinoline produces an antidepressant-like effect in the
      forced swim test and chronic mild stress model of depression in the rat:
      Neurochemical correlates.
AB  - 1,2,3,4-Tetrahydroisoquinoline (TIQ) is an exo- and endogenous amine naturally
      present in mammalian brain which displays antidepressant-like effect in various
      animal models: the forced swim test (FST) and chronic mild stress (CMS) paradigm
      in rats. To elucidate this action we compared the effects of TIQ with imipramine,
      a classic antidepressant drug and one of the most clinically effective. Applied
      behavioral tests showed that TIQ produced an antidepressant-like effect with a
      potency comparable to that of imipramine. TIQ (25-50mg/kg i.p.), similarly to
      imipramine (10-30mg/kg i.p.), reduced the immobility time in FST and completely
      reversed the decrease in sucrose intake caused by CMS in the rat. In addition, in
      order to avoid the possible psychostimulating effect of TIQ we examined the
      influence of its administration on locomotor activity in rats. TIQ, like
      imipramine, produced a reduction in horizontal locomotor activity. This suggested
      that TIQ did not have psychostimulant properties and that prolonged swimming in
      the FST was a result of an increased motivation to escape from the stressful
      situation. The biochemical analyses have shown that TIQ activates monoaminergic
      systems as a reversible monoamine oxidase (MAO) inhibitor and free radical
      scavenger. Beyond the activation of noradrenaline and serotonin systems, TIQ also
      moderately affects the dopamine system. On the basis of the presented behavioral
      and biochemical studies we suggest that TIQ is a potential new antidepressant
      which may be effective for the depression therapy in a clinical setting. 

PMID- 24561049
TI  - Effects of dopamine D(2)-like receptor agonists in mice trained to discriminate
      cocaine from saline: influence of feeding condition.
AB  - In rats, the discriminative stimulus effects of direct- and indirect-acting
      dopamine receptor agonists are mediated by multiple dopamine receptor subtypes
      and the relative contribution of dopamine D2 and D3 receptors to these effects
      varies as a function of feeding condition. In these studies, free-fed and food
      restricted mice were trained to discriminate 10.0mg/kg cocaine using a two-lever
      discrimination procedure in which responding was maintained by food. Both groups
      of mice acquired the discrimination; however, free-fed mice responded at lower
      rates than food-restricted mice. Dopamine D3 receptor agonists, pramipexole and
      quinpirole, increased cocaine-appropriate responding (>85%) in food-restricted,
      but not in free-fed mice. The dopamine D2 receptor agonist, sumanirole, and the
      nonselective dopamine receptor agonist, apomorphine, failed to increase cocaine
      appropriate responding in either group. Free-fed mice were more sensitive than
      food-restricted mice to the rate-decreasing effects of dopamine receptor agonists
      and these effects could not be overcome by increasing the magnitude of
      reinforcement. Because feeding condition did not alter quinpirole-induced
      hypothermia, it is unlikely that differences in the discriminative stimulus or
      rate-decreasing effects of dopamine D2-like receptor agonists were due to
      differences in the pharmacokinetic properties of the drugs. Although these
      results suggest that the discriminative stimulus effects of cocaine are mediated
      by both dopamine D2 and D3 receptors in food-restricted mice, the increased
      sensitivity of free-fed mice to the rate-decreasing effects of dopamine D2-like
      receptor agonists limited conclusions about the impact of feeding conditions on
      the relative contribution of dopamine D2 and D3 receptors to the discriminative
      stimulus effects of cocaine. 

PMID- 24561051
TI  - Molecular evolution of the androgenic hormone in terrestrial isopods.
AB  - In crustaceans, the androgenic gland (AG), thanks to the synthesis of the
      androgenic gland hormone (AGH), controls the differentiation of the primary and
      secondary male sexual characters. In this study, we amplified 12 new AGH cDNAs in
      species belonging to five different families of the infra-order Ligiamorpha of
      terrestrial isopods. Putative essential amino acids for the production of a
      functional AGH protein exhibit signatures of negative selection and are strictly
      conserved including typical proteolytic cleavage motifs, a putative N-linked
      glycosylation motif on the A chains and the eight Cys positions. An insulin-like
      growth factor motif was also identified in Armadillidium AGH sequences. The
      phylogenetic relationships of AGH sequences allowed one to distinguish two main
      clades, corresponding to members of the Armadillidiidae and the Porcellionidae
      families which are congruent with the narrow specificity of AG heterospecific
      grafting. An in-depth understanding of the regulation of AGH expression would
      help deciphering the interaction between Wolbachia, widespread feminizing
      endosymbiotic bacteria in isopods, and the sex differentiation of their hosts. 

PMID- 24561052
TI  - Cost-effectiveness of childhood rotavirus vaccination in Germany.
AB  - BACKGROUND: Rotavirus (RV) causes a highly contagious gastroenteritis especially
      in children under five years of age. Since 2006 two RV-vaccines are available in
      Europe (Rotarix((r)) and RotaTeq((r))). To support informed decision-making
      within the German Standing Committee on Vaccination (STIKO) the cost
      effectiveness of these two vaccines was evaluated for the German healthcare
      setting. METHODS: A Markov model was developed to evaluate the cost-effectiveness
      from the statutory health insurance (SHI) and from the societal perspective. RV
      cases prevented, RV-associated hospitalizations avoided, and quality-adjusted
      life years (QALY) gained were considered as health outcomes. RV-incidences were
      calculated based on data from the national mandatory disease reporting system. RV
      vaccine efficacy was determined as pooled estimates based on data from randomized
      controlled trials. Vaccine list prices and price catalogues were used for cost
      assessment. Effects and costs were discounted with an annual discount rate of 3%.
      RESULTS: The base-case analysis (SHI-perspective) resulted in an incremental cost
      effectiveness and cost-utility ratio for Rotarix((r)) of ? 184 per RV-case
      prevented, ? 2457 per RV-associated hospitalization avoided, and ? 116,973 per
      QALY gained. For RotaTeq((r)), the results were ? 234 per RV-case prevented, ?
      2622 per RV-associated hospitalization avoided, and ? 142,732 per QALY gained.
      Variation of various parameters in sensitivity analyses showed effects on the
      ICERs without changing the overall trend of base-case results. When applying base
      case results to the 2012 birthcohort in Germany with 80% vaccination coverage, an
      estimated 206,000-242,000 RV-cases and 18,000 RV-associated hospitalizations can
      be prevented in this birthcohort over five years for an incremental cost of 44.5
      48.2 million ?. CONCLUSION: Our analyses demonstrate that routine RV-vaccination
      could prevent a substantial number of RV-cases and hospitalizations in the German
      healthcare system, but the saved treatment costs are counteracted by costs for
      vaccination. However, with vaccine prices reduced by ~62-66%, RV-vaccination
      could even become a cost-saving preventive measure.

PMID- 24561053
TI  - Complications associated with laparoscopic adrenalectomy: Description and
      standardized assessment.
AB  - OBJECTIVE: Laparoscopic adrenalectomy (LA) is the procedure of choice for
      surgical management of the adrenal masses. Our objective is to show a
      standardized assessment of perioperative complications in one LA series. MATERIAL
      AND METHODS: 322 LA were performed consecutively between June of 1993 and
      September of 2012 in patients diagnosed with suprarenal tumour. In order to
      evaluate perioperative complications, data were collected prospectively and
      analysed retrospectively. Intraoperative complications were defined using Satava
      classification and Clavien-Dindo classification of postoperative complications.
      RESULTS: Twenty five LA showed perioperative complications (7.3%); 11 (3.2%) were
      intraoperative complications, most of them vascular diaphragmatic lesions (Satava
      Grade 2); and 14 (4.1%) were postoperative complications. Six patients showed
      complications requiring surgery (Clavien IIIa/IIIb) and/or support in Intensive
      Care Unit (Clavien IV). Conversion to open surgery was necessary in one case
      (.3%). Despite all appropriate preoperative endocrine measures were taken, an
      uncontrolled hypertensive crisis and cardio-respiratory arrest recovered were
      developed during surgery in one patient carrier of pheochromocytoma who died from
      massive cerebral infarction at 5 days (Clavien V). CONCLUSIONS: Standardized
      criteria of surgical complications are necessary. Standardization is possible by
      combined application of two tools. We believe that this evaluation concept of the
      surgery morbidity must be used systematically in order to achieve a new standard
      refined, concise and comparative for reports of adverse perioperative events.

PMID- 24561054
TI  - Primary tumor volume should be included in the TNM staging system of
      nasopharyngeal carcinoma.
AB  - TNM staging system based on anatomic location, cranial nerve and conventional
      radiation therapy is currently the widely used classification for nasopharyngeal
      carcinoma (NPC). However, the T classification in separation of primary tumor
      volume fail to predict the radiosensitivity of primary tumor. And with the advent
      of intensity-modulated radiation therapy (IMRT), increasing studies show the
      significance of the primary tumor volume on the treatment outcome of NPC patients
      and primary tumor volume significantly improve the prognostic validity of T
      classification in NPC. What's more, the current T staging system has limitations
      to provide appropriate treatment for different subgroup NPC patients. Therefore,
      we propose that primary tumor volume should be included in the TNM staging system
      of nasopharyngeal carcinoma to guide our clinical decision. 

PMID- 24561055
TI  - Implanted neuroprosthesis for restoring arm and hand function in people with high
      level tetraplegia.
AB  - OBJECTIVE: To develop and apply an implanted neuroprosthesis to restore arm and
      hand function to individuals with high level tetraplegia. DESIGN: Case study.
      SETTING: Clinical research laboratory. PARTICIPANTS: Individuals with spinal cord
      injuries (N=2) at or above the C4 motor level. INTERVENTIONS: The individuals
      were each implanted with 2 stimulators (24 stimulation channels and 4 myoelectric
      recording channels total). Stimulating electrodes were placed in the shoulder and
      arm, being, to our knowledge, the first long-term application of spiral nerve
      cuff electrodes to activate a human limb. Myoelectric recording electrodes were
      placed in the head and neck areas. MAIN OUTCOME MEASURES: Successful installation
      and operation of the neuroprosthesis and electrode performance, range of motion,
      grasp strength, joint moments, and performance in activities of daily living.
      RESULTS: The neuroprosthesis system was successfully implanted in both
      individuals. Spiral nerve cuff electrodes were placed around upper extremity
      nerves and activated the intended muscles. In both individuals, the
      neuroprosthesis has functioned properly for at least 2.5 years postimplant. Hand,
      wrist, forearm, elbow, and shoulder movements were achieved. A mobile arm support
      was needed to support the mass of the arm during functional activities. One
      individual was able to perform several activities of daily living with some
      limitations as a result of spasticity. The second individual was able to
      partially complete 2 activities of daily living. CONCLUSIONS: Functional
      electrical stimulation is a feasible intervention for restoring arm and hand
      functions to individuals with high tetraplegia. Forces and movements were
      generated at the hand, wrist, elbow, and shoulder that allowed the performance of
      activities of daily living, with some limitations requiring the use of a mobile
      arm support to assist the stimulated shoulder forces.

PMID- 24561056
TI  - Body temperature is elevated and linked to fatigue in relapsing-remitting
      multiple sclerosis, even without heat exposure.
AB  - OBJECTIVES: To investigate whether (1) resting body temperature is elevated in
      patients with relapsing-remitting multiple sclerosis (RRMS) relative to healthy
      individuals and patients with secondary progressive multiple sclerosis (SPMS),
      and (2) warmer body temperature is linked to worse fatigue in patients with RRMS.
      DESIGN: Cross-sectional study. SETTING: Climate-controlled laboratory (~22
      degrees C) within a nonprofit medical rehabilitation research center.
      PARTICIPANTS: Patients with RRMS (n=50), matched healthy controls (n=40), and
      patients with SPMS (n=22). INTERVENTION: Not applicable. MAIN OUTCOME MEASURES:
      Body temperature was measured with an aural infrared thermometer (normative body
      temperature for this thermometer, 36.75 degrees C), and differences were compared
      across patients with RRMS and SPMS and healthy persons. Patients with RRMS
      completed measures of general fatigue (Fatigue Severity Scale [FSS]), as well as
      physical and cognitive fatigue (Modified Fatigue Impact Scale [MFIS]). RESULTS:
      There was a large effect of group (P<.001, etap(2)=.132) whereby body temperature
      was higher in patients with RRMS (37.04 degrees +/-.27 degrees C) relative to
      healthy controls (36.83 degrees +/-.33 degrees C; P=.009) and patients with SPMS
      (36.75 degrees +/-.39 degrees C; P=.001). Warmer body temperature in patients
      with RRMS was associated with worse general fatigue (FSS; rp=.315, P=.028) and
      physical fatigue (physical fatigue subscale of the MFIS; rp=.318, P=.026), but
      not cognitive fatigue (cognitive fatigue subscale of the MIFS; rp=-.017, P=.909).
      CONCLUSIONS: These are the first-ever demonstrations that body temperature is
      elevated endogenously in patients with RRMS and linked to worse fatigue. We
      discuss these findings in the context of failed treatments for fatigue in RRMS,
      including several failed randomized controlled trials (RCTs) of stimulants
      (modafinil). In contrast, our findings may help explain how RCTs of cooling
      garments and antipyretics (aspirin) have effectively reduced MS fatigue, and
      encourage further research on cooling/antipyretic treatments of fatigue in RRMS.

PMID- 24561057
TI  - Effects of repetitive peripheral magnetic stimulation on upper-limb spasticity
      and impairment in patients with spastic hemiparesis: a randomized, double-blind,
      sham-controlled study.
AB  - OBJECTIVE: To investigate short-term and long-term effects of repetitive
      peripheral magnetic stimulation (rpMS) on spasticity and motor function. DESIGN:
      Monocentric, randomized, double-blind, sham-controlled trial. SETTING: Neurologic
      rehabilitation hospital. PARTICIPANTS: Patients (N=66) with severe hemiparesis
      and mild to moderate spasticity resulting from a stroke or a traumatic brain
      injury. The average time +/- SD since injury for the intervention groups was 26
      +/- 71 weeks or 37 +/- 82 weeks. INTERVENTIONS: rpMS for 20 minutes or sham
      stimulation with subsequent occupational therapy for 20 minutes, 2 times a day,
      over a 2-week period. MAIN OUTCOME MEASURES: Modified Tardieu Scale and Fugl
      Meyer Assessment (arm score), assessed before therapy, at the end of the 2-week
      treatment period, and 2 weeks after study treatment. Additionally, the Tardieu
      Scale was assessed after the first and before the third therapy session to
      determine any short-term effects. RESULTS: Spasticity (Tardieu >0) was present in
      83% of wrist flexors, 62% of elbow flexors, 44% of elbow extensors, and 10% of
      wrist extensors. Compared with the sham stimulation group, the rpMS group showed
      short-term effects on spasticity for wrist flexors (P=.048), and long-term
      effects for elbow extensors (P<.045). Arm motor function (rpMS group: median 5 [4
      27]; sham group: median 4 [4-9]) did not significantly change over the study
      period in either group, whereas rpMS had a positive effect on sensory function.
      CONCLUSIONS: Therapy with rpMS increases sensory function in patients with severe
      limb paresis. The magnetic stimulation, however, has limited effect on spasticity
      and no effect on motor function.

PMID- 24561058
TI  - Comorbidity of pain and depression among persons with traumatic brain injury.
AB  - OBJECTIVE: To assess the prevalence of pain, depression, and comorbid pain and
      depression among a civilian sample of persons with traumatic brain injury (TBI).
      DESIGN: Longitudinal survey design with 1-year follow-up. SETTING: Inpatient
      rehabilitation and the community. PARTICIPANTS: Participants (N=158) admitted to
      inpatient rehabilitation after moderate to severe TBI. INTERVENTIONS: Not
      applicable. MAIN OUTCOME MEASURES: Depression was assessed with the Patient
      Health Questionnaire-9 (PHQ-9); pain was assessed with a numerical rating scale
      from 0 (no pain) to 10 (worst pain). Participants who reported average pain >= 4
      were classified as having pain, and participants with PHQ-9 scores >= 10 were
      classified as depressed. RESULTS: Both pain and depression were more prevalent at
      baseline assessment (pain: 70%; depression: 31%) than at year 1 (pain: 34%;
      depression: 22%). Comorbid pain and depression declined from 27% at baseline to
      18% at year 1. Pain was significantly associated with depression at baseline
      (relative risk: 2.62, P=.003) and at year 1 (relative risk: 7.98, P<.001).
      CONCLUSIONS: Pain and depression are common and frequently co-occur in persons
      with TBI. Although their frequency declined over the first year after injury, the
      strength of their association increased. Assessment and treatment of both
      conditions simultaneously may lead to improved outcomes, both early after TBI and
      over time.

PMID- 24561059
TI  - Health-related quality of life 3 years after moderate to severe traumatic brain
      injury: a prospective cohort study.
AB  - OBJECTIVES: To evaluate the time course of health-related quality of life (HRQoL)
      after moderate to severe traumatic brain injury (TBI) and to identify its
      predictors. DESIGN: Prospective cohort study with follow-up measurements at 3, 6,
      12, 18, 24, and 36 months after TBI. SETTING: Patients with moderate to severe
      TBI discharged from 3 level-1 trauma centers. PARTICIPANTS: Patients (N=97, 72%
      men) with a mean age +/- SD of 32.8+/-13.0 years (range, 18-65y), hospitalized
      with moderate (23%) or severe (77%) TBI. INTERVENTIONS: Not applicable. MAIN
      OUTCOME MEASURES: HRQoL was measured with the Medical Outcomes Study 36-Item
      Short-Form Health Survey (SF-36), functional outcomes with the Glasgow Outcome
      Scale (GOS), Barthel Index, FIM, and Functional Assessment Measure, and mood with
      the Wimbledon Self-Report Scale. RESULTS: The SF-36 domains showed significant
      improvement over time for Physical Functioning (P<.001), Role Physical (P<.001),
      Bodily Pain (P<.001), Social Functioning (P<.001), and Role Emotional (P=.024),
      but not for General Health (P=.263), Vitality (P=.530), and Mental Health
      (P=.138). Over time there was significant improvement in the Physical Component
      Summary (PCS) score, whereas the Mental Component Summary (MCS) score remained
      stable. At 3-year follow-up, HRQoL of patients with TBI was the same as that in
      the Dutch normative population. Time after TBI, hospital length of stay (LOS),
      FIM, and GOS were independent predictors of the PCS, whereas LOS and mood were
      predictors of the MCS. CONCLUSIONS: After TBI, the physical component of HRQoL
      showed significant improvement over time, whereas the mental component remained
      stable. Problems of disease awareness seem to play a role in self-reported mental
      HRQoL. After TBI, mood status is a better predictor of the mental component of
      HRQoL than functional outcome, implying that mood should be closely monitored
      during and after rehabilitation.

PMID- 24561060
TI  - Predictors of participation enfranchisement after spinal cord injury: the
      mediating role of depression and moderating role of demographic and injury
      characteristics.
AB  - OBJECTIVES: (1) To examine the mediating effects of depressive symptoms on the
      relations between employment, grief, depression treatment, and participation
      enfranchisement after spinal cord injury (SCI); and (2) to examine the moderating
      role of demographic and injury characteristics, including sex, race, marital
      status, education, and injury level, and completeness on these relations. DESIGN:
      Cross-sectional survey as part of the Project to Improve Symptoms and Mood after
      SCI (PRISMS). SETTING: Rehabilitation facilities. PARTICIPANTS: Persons with SCI
      (N=522; average age, 42 y; 76% men; 64% white; 64% completed at least a high
      school education) enrolled from 2007 to 2011. INTERVENTIONS: Not applicable. MAIN
      OUTCOME MEASURE: Participation enfranchisement. RESULTS: The final model fit the
      data relatively well (comparative fix index=.939; Tucker-Lewis Index=.894; root
      mean square error of approximation=.066; 90% confidence interval, .043-.089),
      explaining 32% of the variance in participation enfranchisement. Enfranchisement
      was positively related to employment and negatively related to depression.
      Grieving the loss of a loved one and the use of an antidepressant or
      psychotherapy were related to participation enfranchisement; these relations were
      mediated by depressive symptoms. Multigroup analyses supported the model's
      invariance across sex, marital status, severity of injury, and level of injury.
      CONCLUSIONS: Depression appears to mediate the influence of employment, grief,
      and depression treatments on participation enfranchisement after SCI. These
      relations are applicable regardless of sex, marital status, and injury
      completeness and level. These findings highlight efforts to improve the detection
      and treatment of depression in SCI rehabilitation programs that may enhance
      participation.

PMID- 24561063
TI  - Role of acetylcholine in control of sexual behavior of male and female mammals.
AB  - The results of studies using systemic or central applications of cholinergic
      drugs suggest that acetylcholine makes important contributions to the
      neurochemical control of male- and female-typical reproductive behaviors. In
      males, cholinergic control seems largely specific to some elements or aspects of
      copulatory behavior that can vary significantly across species. Synapses in or
      near the medial preoptic area represent part of this mechanism, but the entire
      system appears to extend more widely, perhaps especially to one or more
      structures flanking some part of the lateral ventricle. In females, the lordosis
      response that essentially defines sexual receptivity is clearly responsive to
      cholinergic drugs. The same seems likely to be true of other elements of female
      sexual behavior, but additional studies will be needed to confirm this. Changes
      in cholinergic activity may help to mediate estrogenic effects on female sexual
      behavior. However, estrogen exposure can increase or decrease cholinergic
      effects, suggesting a relationship that is complex and requires further analysis.
      Also presently unclear is the localization of the cholinergic effects on female
      sexual responses. Though periventricular sites again have been implicated, their
      identity is presently unknown. This review discusses these and other aspects of
      the central cholinergic systems affecting male and female sexual behaviors.

PMID- 24561061
TI  - MicroRNAs in pancreatic malignancy: progress and promises.
AB  - Despite progress in recent years, pancreatic cancer still remains a major
      clinical challenge. Its incidence and mortality rates have been on consistent
      rise underscoring the critical need for novel diagnostic, prognostic and
      therapeutic tools for its effective management. Recent studies have demonstrated
      that microRNAs (miRNAs/miRs) are deregulated in a variety of malignancies,
      including pancreatic cancer, and play a significant role in the initiation,
      progression and metastasis. Furthermore, their vital involvement in the
      therapeutic resistance of cancer has also been established. Hence, there has been
      enormous interest worldwide in investigating the roles of miRNAs in pancreatic
      cancer pathogenesis and exploiting their utility for clinical benefit. In this
      review, we summarize current knowledge on the role of miRNAs in pancreatic cancer
      and discuss their potential use as diagnostic and prognostic biomarkers, and as
      novel targets for development of effective therapeutic strategies. 

PMID- 24561062
TI  - Neurogenesis in the striatum of the adult human brain.
AB  - In most mammals, neurons are added throughout life in the hippocampus and
      olfactory bulb. One area where neuroblasts that give rise to adult-born neurons
      are generated is the lateral ventricle wall of the brain. We show, using
      histological and carbon-14 dating approaches, that in adult humans new neurons
      integrate in the striatum, which is adjacent to this neurogenic niche. The
      neuronal turnover in the striatum appears restricted to interneurons, and
      postnatally generated striatal neurons are preferentially depleted in patients
      with Huntington's disease. Our findings demonstrate a unique pattern of
      neurogenesis in the adult human brain. 

PMID- 24561064
TI  - Involvement of opioid receptors in the systemic and peripheral antinociceptive
      actions of ellagic acid in the rat formalin test.
AB  - Ellagic acid (EA) produced antinociceptive and anti-inflammatory effects. This
      study was conducted to investigate the involvement of opioid receptors in the
      systemic and peripheral antinociceptive effects of EA after intraperitoneal
      (i.p.) and intraplantar (i.pl.) administration in the rat formalin assay. The
      results showed that i.p. administration of EA (1-30 mg/kg) dose-dependently
      attenuated flinching number in both early and late phases of the formalin test
      with mean ED50 values of 1.86 and 0.52 mg/kg, respectively. Moreover, this effect
      of EA at a dose of 30 mg/kg was comparable to that of morphine (5mg/kg; i.p.) and
      indomethacin (10mg/kg; i.p.). It was also demonstrated that administration of EA
      (30-300 MUg/paw; i.pl.) resulted in dose-dependent peripheral antinociception
      against early and late phases of formalin-induced nociception with mean ED50
      values of 47.64 and 71.78 MUg/paw, respectively. The antinociception produced by
      the i.pl. injection was due to a local action, as its administration in the
      contralateral paw was ineffective. Furthermore, pre-treatment with naloxone, a
      non-selective opioid antagonist, significantly alleviated the systemic and
      peripheral antinociceptive effects of EA. Also, EA treatment had no effect on the
      motor activity of rats when tested in open-field task. Our data suggest that the
      systemic and peripheral antinociception activities of EA were mediated through
      the opioid receptors in the periphery and also in the central nervous system.

PMID- 24561065
TI  - Endothelin receptor type B agonist, IRL-1620, prevents beta amyloid (Abeta)
      induced oxidative stress and cognitive impairment in normal and diabetic rats.
AB  - Alzheimer's disease (AD) is a progressive brain disorder leading to impairment of
      learning and memory. Amyloid beta (Abeta) induced oxidative stress has been
      implicated in the initiation and progression of AD. Endothelin (ET) and its
      receptors have been considered as therapeutic targets for AD. Recent studies
      indicate that stimulation of ETB receptors may provide neuroprotection. The
      purpose of this study was to determine the preventative effect of selectively
      stimulating ETB receptors on cognitive impairment and oxidative stress in Abeta
      treated non-diabetic and diabetic (induced by streptozotocin) rats. Rats were
      concurrently treated with Abeta1-40 (day 1, 7 and 14) and either saline, IRL-1620
      (an ETB agonist), and/or BQ788 (an ETB antagonist) daily for 14 days in the
      lateral cerebral ventricles using sterotaxically implanted cannula; experiments
      were performed on day 15. Abeta treatment produced a significant (p<0.0001)
      increase of 360% and 365% in malondialdehyde levels (a marker of lipid
      peroxidation) in non-diabetic and diabetic rats, respectively, compared to sham
      group. Antioxidants (superoxide dismutase and reduced glutathione) decreased
      following Abeta treatment compared to sham group. Treatment with IRL-1620
      reversed these effects, indicating that ETB receptor stimulation reduces
      oxidative stress injury following Abeta treatment. In Morris swim task, Abeta
      treated rats showed impairment in spatial memory. Rats treated with IRL-1620
      significantly reduced the cognitive impairment induced by Abeta. BQ788 treatment
      completely blocked IRL-1620 induced reduction in oxidative stress and cognitive
      impairment. Results of the present study demonstrate that IRL-1620 improved both
      acquisition (learning) and retention (memory) on water maze task and reduced
      oxidative stress parameters. It can be speculated that ETB receptor stimulation
      prevents cognitive impairment and may be useful in neurodegenerative diseases.

PMID- 24561066
TI  - Fish oil provides a sustained antiamnesic effect after acute, transient forebrain
      ischemia but not after chronic cerebral hypoperfusion in middle-aged rats.
AB  - We reported that fish oil (FO) abolishes retrograde amnesia consistently
      following transient global cerebral ischemia (TGCI) in young rats, provided it
      covered the first days prior to and after ischemia. Here, we further evaluated
      whether FO given post-ischemia in older rats (15-18 months old) is equally
      effective in facilitating memory recovery. We also tested whether the antiamnesic
      effect of FO observed after TGCI can be reproduced after chronic cerebral
      hypoperfusion (CCH). FO (300 mg/kg docosahexaenoic acid [DHA]) was delivered
      orally 4h after TGCI and continued once per day for 9 days. In the CCH group, FO
      treatment began soon after the first stage of 4-VO/ICA and continued daily for 43
      days. Two weeks after surgery, the animals were tested for retrograde memory
      performance across 5 weeks. Both TGCI and CCH caused persistent memory impairment
      and hippocampal and cortical neurodegeneration. TGCI-induced retrograde amnesia
      was reversed by FO, an effect that was sustained for at least 5 weeks after
      discontinuing treatment. In contrast, the memory deficit caused by CCH remained
      unchanged after FO treatment. Both hippocampal and cortical damage was not
      alleviated by FO. We conclude that the FO-mediated antiamnesic effect following
      TGCI can be extended to older rats, even when the treatment begins 4h
      postischemia. Such efficacy was not reproduced after CCH. Therefore, the present
      results support the notion that FO may have therapeutic utility in treating
      learning/memory dysfunction after acute/transient cerebral ischemia and suggest
      that such benefits may not apply when a state of chronic cerebrovascular
      insufficiency is present.

PMID- 24561069
TI  - Dopaminergic manipulations and its effects on neurogenesis and motor function in
      a transgenic mouse model of Huntington's disease.
AB  - Huntington's disease (HD) is an inherited neurodegenerative disorder that is
      classically defined by a triad of movement and cognitive and psychiatric
      abnormalities with a well-established pathology that affects the dopaminergic
      systems of the brain. This has classically been described in terms of an early
      loss of dopamine D2 receptors (D2R), although interestingly the treatments most
      effectively used to treat patients with HD block these same receptors. We
      therefore sought to examine the dopaminergic system in HD not only in terms of
      striatal function but also at extrastriatal sites especially the hippocampus,
      given that transgenic (Tg) mice also exhibit deficits in hippocampal-dependent
      cognitive tests and a reduction in adult hippocampal neurogenesis. We showed that
      there was an early reduction of D2R in both the striatum and dentate gyrus (DG)
      of the hippocampus in the R6/1 transgenic HD mouse ahead of any overt motor signs
      and before striatal neuronal loss. Despite downregulation of D2Rs in these sites,
      further reduction of the dopaminergic input to these sites by either medial
      forebrain bundle lesions or receptor blockade using sulpiride was able to improve
      both deficits in motor performance and adult hippocampal neurogenesis. In
      contrast, a reduction in dopaminergic innervation of the neurogenic niches
      resulted in impaired neurogenesis in healthy WT mice. This study therefore
      provides evidence that D2R blockade improves hippocampal and striatal deficits in
      HD mice although the underlying mechanism for this is unclear, and suggests that
      agents working within this network may have greater effects than previously
      thought. 

PMID- 24561068
TI  - Slc26a4-insufficiency causes fluctuating hearing loss and stria vascularis
      dysfunction.
AB  - SLC26A4 mutations can cause a distinctive hearing loss phenotype with sudden
      drops and fluctuation in patients. Existing Slc26a4 mutant mouse lines have a
      profound loss of hearing and vestibular function, with severe inner ear
      malformations that do not model this human phenotype. In this study, we generated
      Slc26a4-insufficient mice by manipulation of doxycycline administration to a
      transgenic mouse line in which all Slc26a4 expression was under the control of
      doxycycline. Doxycycline was administered from conception to embryonic day 17.5,
      and then it was discontinued. Auditory brainstem response thresholds showed
      significant fluctuation of hearing loss from 1 through 3months of age. The
      endocochlear potential, which is required for inner ear sensory cell function,
      correlated with auditory brainstem response thresholds. We observed degeneration
      of stria vascularis intermediate cells, the cells that generate the endocochlear
      potential, but no other abnormalities within the cochlea. We conclude that
      fluctuations of hearing result from fluctuations of the endocochlear potential
      and stria vascularis dysfunction in Slc26a4-insufficient mouse ears. This model
      can now be used to test potential interventions to reduce or prevent sudden
      hearing loss or fluctuation in human patients. Our strategy to generate a
      hypomorphic mouse model utilizing the tet-on system will be applicable to other
      diseases in which a hypomorphic allele is needed to model the human phenotype. 

PMID- 24561071
TI  - The Pampas fox (Lycalopex gymnocercus) as new definitive host for Spirometra
      erinacei (Cestoda: Diphyllobothriidae).
AB  - Spirometra erinacei, Faust, Campbell and Kellogg, 1929, is a pseudophyllidean
      cestode of the family Diphyllobothriidae. The genus Spirometra is cosmopolitan
      and these parasites infect carnivores, specially felids and canids. In Argentina,
      S. erinacei and S. mansonoides have been reported sporadically only in domestic
      definitive hosts. The Pampas fox, Lycalopex gymnocercus, is the most abundant
      native carnivore in southern South America, where it inhabits grasslands and open
      woodlands and areas highly modified by extensive ranching and agricultural
      activities. This report describes the first finding of S. erinacei infecting
      Pampas fox, and provides an estimate prevalence of this cestode in rural areas of
      southern Buenos Aires province, Argentina based on 78 complete Pampas fox
      intestine samples analysis. This study found a 15.4% of prevalence of S. erinacei
      in small intestine (adult stage) and a 21.8% in fecal samples (egg stage). In the
      present work, the first case of S. erinacei in a wild definitive host from
      Argentina was reported expanding the list of definitive hosts of S. erinacei in
      South America. 

PMID- 24561067
TI  - Megalencephalic leukoencephalopathy with subcortical cysts protein-1 modulates
      endosomal pH and protein trafficking in astrocytes: relevance to MLC disease
      pathogenesis.
AB  - Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a rare
      leukodystrophy caused by mutations in the gene encoding MLC1, a membrane protein
      mainly expressed in astrocytes in the central nervous system. Although MLC1
      function is unknown, evidence is emerging that it may regulate ion fluxes. Using
      biochemical and proteomic approaches to identify MLC1 interactors and elucidate
      MLC1 function we found that MLC1 interacts with the vacuolar ATPase (V-ATPase),
      the proton pump that regulates endosomal acidity. Because we previously showed
      that in intracellular organelles MLC1 directly binds Na, K-ATPase, which controls
      endosomal pH, we studied MLC1 endosomal localization and trafficking and MLC1
      effects on endosomal acidity and function using human astrocytoma cells
      overexpressing wild-type (WT) MLC1 or MLC1 carrying pathological mutations. We
      found that WT MLC1 is abundantly expressed in early (EEA1(+), Rab5(+)) and
      recycling (Rab11(+)) endosomes and uses the latter compartment to traffic to the
      plasma membrane during hyposmotic stress. We also showed that WT MLC1 limits
      early endosomal acidification and influences protein trafficking in astrocytoma
      cells by stimulating protein recycling, as revealed by FITC-dextran measurement
      of endosomal pH and transferrin protein recycling assay, respectively. WT MLC1
      also favors recycling to the plasma-membrane of the TRPV4 cation channel which
      cooperates with MLC1 to activate calcium influx in astrocytes during hyposmotic
      stress. Although MLC disease-causing mutations differentially affect MLC1
      localization and trafficking, all the mutated proteins fail to influence
      endosomal pH and protein recycling. This study demonstrates that MLC1 modulates
      endosomal pH and protein trafficking suggesting that alteration of these
      processes contributes to MLC pathogenesis. 

PMID- 24561072
TI  - Lymphedema in a 7-year-old boy infected with Wuchereria bancrofti in Sierra
      Leone: a case report.
AB  - We present a case of congenital lymphedema in a 7-year-old boy in Sierra Leone
      with active filarial infection and penile edema. The genital edema with onset at
      6 months of age may have been due to a congenital abnormality in lymphatic
      drainage. Other possible causes of childhood lymphedema, including Milroy's
      disease, are discussed. 

PMID- 24561070
TI  - Exonic microdeletions of the gephyrin gene impair GABAergic synaptic inhibition
      in patients with idiopathic generalized epilepsy.
AB  - Gephyrin is a postsynaptic scaffolding protein, essential for the clustering of
      glycine and gamma-aminobutyric acid type-A receptors (GABAARs) at inhibitory
      synapses. An impairment of GABAergic synaptic inhibition represents a key pathway
      of epileptogenesis. Recently, exonic microdeletions in the gephyrin (GPHN) gene
      have been associated with neurodevelopmental disorders including autism spectrum
      disorder, schizophrenia and epileptic seizures. Here we report the identification
      of novel exonic GPHN microdeletions in two patients with idiopathic generalized
      epilepsy (IGE), representing the most common group of genetically determined
      epilepsies. The identified GPHN microdeletions involve exons 5-9 (Delta5-9) and 2
      3 (Delta2-3), both affecting the gephyrin G-domain. Molecular characterization of
      the GPHN Delta5-9 variant demonstrated that it perturbs the clustering of regular
      gephyrin at inhibitory synapses in cultured mouse hippocampal neurons in a
      dominant-negative manner, resulting in a significant loss of gamma2-subunit
      containing GABAARs. GPHN Delta2-3 causes a frameshift resulting in a premature
      stop codon (p.V22Gfs*7) leading to haplo-insufficiency of the gene. Our results
      demonstrate that structural exonic microdeletions affecting the GPHN gene
      constitute a rare genetic risk factor for IGE and other neuropsychiatric
      disorders by an impairment of the GABAergic inhibitory synaptic transmission.

PMID- 24561073
TI  - An ecological study of Bithynia snails, the first intermediate host of
      Opisthorchis viverrini in northeast Thailand.
AB  - Infection with the food-borne trematodiasis, liver fluke Opisthorchis viverrini,
      is a major public health concern in Southeast Asia. While epidemiology and
      parasitic incidence in humans are well studied, ecological information on the O.
      viverrini intermediate hosts remains limited. This study aimed to investigate the
      factors affecting the distribution and abundance of the first intermediate host,
      Bithynia siamensis goniomphalos snails. Water quality and snails were sampled in
      31 sites in Muang District, Khon Kaen Province, Thailand from June 2012 to
      January 2013 to characterize the B.s. goniomphalos snail habitats. Species
      relative abundance and Shannon's diversity and evenness indices were employed to
      describe snail compositions and diversities across different habitat types.
      Statistical analyses were conducted to examine the extent to which the water
      quality variables and species interactions account for the relative abundance of
      B.s. goniomphalos snails. The results showed that the freshwater habitats of
      ponds, streams and rice paddies possessed significantly different abiotic water
      qualities, with water temperature and pH showing distinct statistical differences
      (P<0.05). Different habitats had different snail diversity and species evenness,
      with high B.s. goniomphalos snail abundance at rice paddy habitats. The
      differences in snail abundance might be due to the distinct sets of abiotic water
      qualities associated with each habitat types. The relative abundance of B.s.
      goniomphalos snails was found to be negatively correlated with that of
      Filopaludina martensi martensi snails (r=-0.46, P<0.05), underscoring the
      possible influence of species interaction on B.s. goniomphalos snail population.
      Field work observations revealed that rice planting seasons and irrigation could
      regulate snail population dynamics at rice paddy habitats. This study provides
      new ecological insights into the factors affecting Bithynia snail distribution
      and abundance. It bridges the knowledge gap in O. viverrini disease ecology and
      highlights the potential effect of anthropogenic irrigation practices on B.s.
      goniomphalos snail ecology. 

PMID- 24561074
TI  - Effect of night time-intervals, height of traps and lunar phases on sand fly
      collection in a highly endemic area for canine leishmaniasis.
AB  - The activity of phlebotomine sand flies was monitored in a sub-urban area of
      Sicily in order to acquire data on seasonality and to elucidate the effect of the
      night time-intervals, height of traps from ground and lunar phases on the
      abundance of the capture. The study was conducted in the farm of the University
      of Messina (Italy). Light traps were placed as in the following: biweekly, from
      dusk to dawn, and from May to November; for three consecutive nights from 18:00
      to 6:00, with the net bag being changed every 2h; for 30 days, at different
      heights from 18:00 to 6:00. A total of five species (i.e., Phlebotomus
      perniciosus, Phlebotomus neglectus, Phlebotomus sergenti, Phlebotomus perfiliewi,
      and Sergentomyia minuta), three of which are proven vectors of Leishmania
      infantum, were captured. The most abundant species was P. perniciosus (73.3%)
      followed by S. minuta (23.3%). The highest number of phlebotomine sand flies was
      collected in August and September with a peak of collection recorded in the
      evening (i.e., from 20:01 to 22.00). The number of phlebotomine sand flies
      collected at 50cm above the ground was significantly higher (P=0.041) than that
      captured at 150cm. Results of this study shed light on the ecology of main
      phlebotomine species in the Mediterranean area, and on the influence of some
      factors, such as time and height of traps, on the light trap capture efficiency. 

PMID- 24561076
TI  - Comments on self-inflicted fatal shotgun wound from a homemade weapon.

PMID- 24561075
TI  - Submicroscopic infections among children with adequate clinical and
      parasitological response (ACPR).
AB  - The aim of the study was to re-assess the treatment outcomes of Gabonese
      children, treated with sulfadoxine-pyrimethamine (SP) and artesunate-mefloquine
      (AM) and categorized by microscopy as adequate clinical and parasitological
      response (ACPR), using polymerase chain reaction (PCR). Dried blood spots were
      collected at day 0 and day 28 and stevor gene amplification was performed to
      detect Plasmodium falciparum infections. Plasmodial DNA was found in 27.5%
      (n=19/69) of the isolates collected at day 28; this proportion was 34.3%
      (n=12/35) in the SP group and 20.6% (n=7/34) in the AM group. This study
      underlines the need of an accurate and more appropriate technique such as PCR to
      evaluate antimalarial drug efficacy during clinical trials. 

PMID- 24561077
TI  - EphA2 knockdown attenuates atherosclerotic lesion development in ApoE(-/-) mice.
AB  - BACKGROUND: The inflammatory response of vascular endothelial cells plays
      important roles in the initiation and progression of atherosclerotic lesions.
      EphA2 receptor activation promotes the endothelial cell inflammatory response,
      and its expression is increased in the endothelial cell layer of atherosclerotic
      plaques. However, the association between EphA2 and atherosclerosis has not been
      determined. METHODS: Eight-week-old male ApoE(-/-) mice were systemically
      infected with adenoassociated virus serotype 9 carrying a small hairpin RNA
      specifically targeting the EphA2 gene to knock down EphA2 expression in aortic
      endothelial cells. These mice were then fed a high-cholesterol diet for 12 weeks.
      Blood was collected for the measurement of plasma lipids. The aortas were
      harvested to evaluate the atherosclerotic lesion size, macrophage components, and
      expression of proinflammatory genes using Oil Red O staining, immunofluorescence
      staining, and molecular biology analysis. RESULTS: The lesions formed in the
      entire aorta and aortic sinus of the ApoE(-/-) mice with EphA2 knockdown were
      significantly smaller than those in the control mice (10.7%+/-3.1% versus 25.1%+/
      4.2%; 0.51+/-0.02mm(2) versus 0.85+/-0.03mm(2); n=10; P<.05). Furthermore, the
      lesions in the ApoE(-/-) mice with EphA2 knockdown displayed reduced inflammation
      compared with the control mice, as reflected by the decreased macrophage
      infiltration (8.2%+/-2.9% versus 22.7%+/-4%; n=10; P<.05); decreased nuclear
      factor-kappabeta activation; and diminished expression of vascular cell adhesion
      molecule-1, E-selectin, and monocyte chemotactic protein-1 (all P<.05).
      CONCLUSIONS: Our data demonstrate that the EphA2 receptor silencing attenuates
      the extent and inflammation of atherosclerotic lesions in ApoE(-/-) mice. Thus,
      EphA2 knockdown in endothelial cells represents a novel therapeutic strategy for
      patients with atherosclerosis.

PMID- 24561078
TI  - Consumer-mediated health information exchanges: the 2012 ACMI debate.
AB  - The American College of Medical Informatics (ACMI) sponsors periodic debates
      during the American Medical Informatics Fall Symposium to highlight important
      informatics issues of broad interest. In 2012, a panel debated the following
      topic: "Resolved: Health Information Exchange Organizations Should Shift Their
      Principal Focus to Consumer-Mediated Exchange in Order to Facilitate the Rapid
      Development of Effective, Scalable, and Sustainable Health Information
      Infrastructure." Those supporting the proposition emphasized the need for
      consumer-controlled community repositories of electronic health records (health
      record banks) to address privacy, stakeholder cooperation, scalability, and
      sustainability. Those opposing the proposition emphasized that the current
      healthcare environment is so complex that development of consumer control will
      take time and that even then, consumers may not be able to mediate their
      information effectively. While privately each discussant recognizes that there
      are many sides to this complex issue, each followed the debater's tradition of
      taking an extreme position in order emphasize some of the polarizing aspects in
      the short time allotted them. In preparing this summary, we sought to convey the
      substance and spirit of the debate in printed form. Transcripts of the actual
      debate were edited for clarity, and appropriate supporting citations were added
      for the further edification of the reader. 

PMID- 24561079
TI  - Airway management and out-of-hospital cardiac arrest outcome in the CARES
      registry.
AB  - BACKGROUND: Optimal out of hospital cardiac arrest (OHCA) airway management
      strategies remain unclear. We compared OHCA outcomes between patients receiving
      endotracheal intubation (ETI) versus supraglottic airway (SGA), and between
      patients receiving [ETI or SGA] and those receiving no advanced airway. METHODS:
      We studied adult OHCA in the Cardiac Arrest Registry to Enhance Survival (CARES).
      Primary exposures were ETI, SGA, or no advanced prehospital airway placed.
      Primary outcomes were sustained ROSC, survival to hospital admission, survival to
      hospital discharge, and neurologically-intact survival to hospital discharge
      (cerebral performance category 1-2). Propensity scores characterized the
      probability of receiving ETI, SGA, or no advanced airway. We adjusted for Utstein
      confounders. Multivariable random effects regression accounted for clustering by
      EMS agency. We compared outcomes between (1) ETI vs. SGA, and (2) [no advanced
      airway] vs. [ETI or SGA]. RESULTS: Of 10,691 OHCA, 5591 received ETI, 3110 SGA,
      and 1929 had no advanced airway. Unadjusted neurologically-intact survival was:
      ETI 5.4%, SGA 5.2%, no advanced airway 18.6%. Compared with SGA, ETI achieved
      higher sustained ROSC (OR 1.35; 95%CI 1.19-1.54), survival to hospital admission
      (1.36; 1.19-1.55), hospital survival (1.41; 1.14-1.76) and hospital discharge
      with good neurologic outcome (1.44; 1.10-1.88). Compared with [ETI or SGA],
      patients receiving no advanced airway attained higher survival to hospital
      admission (1.31; 1.16-1.49), hospital survival (2.96; 2.50-3.51) and hospital
      discharge with good neurologic outcome (4.24; 3.46-5.20). CONCLUSION: In CARES,
      survival was higher among OHCA receiving ETI than those receiving SGA, and for
      patients who received no advanced airway than those receiving ETI or SGA.

PMID- 24561080
TI  - Editorial comment.

PMID- 24561081
TI  - Cyclic tensile force up-regulates BMP-2 expression through MAP kinase and COX
      2/PGE2 signaling pathways in human periodontal ligament cells.
AB  - Periodontal ligament cells play important roles in the homeostasis of periodontal
      tissue by mechanical stress derived from mastication, such as tension,
      compression, fluid shear, and hydrostatic force. In the present study, we showed
      that cyclic tensile force increased the gene expression level of bone
      morphogenetic protein (BMP)-2, a crucial regulator of mineralization, in human
      periodontal ligament cells using real-time PCR. Signaling inhibitors,
      PD98059/U0126 (extracellular signal-regulated kinase (ERK) inhibitors) and
      SB203580/SB202190 (p38 inhibitors), revealed that tensile force-mediated BMP-2
      expression was dependent on activation of the ERK1/2 and p38 mitogen-activated
      protein (MAP) kinase pathways. Cyclic tensile force also induced cyclooxygenase-2
      (COX-2) gene expression in a manner dependent on ERK1/2 and p38 MAP kinase
      pathways, and induced prostaglandin E2 (PGE2) biosynthesis. NS-398, a COX-2
      inhibitor, significantly reduced tensile force-mediated BMP-2 expression,
      indicating that PGE2 synthesized by COX-2 may be involved in the BMP-2 induction.
      The inhibitory effect of NS-398 was completely restored by the addition of
      exogenous PGE2. However, stimulation with PGE2 alone in the absence of tensile
      force had no effect on the BMP-2 induction, indicating that some critical
      molecule(s) other than COX-2/PGE2 may be required for cyclic tensile force
      mediated BMP-2 induction. Collectively, the results indicate that cyclic tensile
      force activates ERK1/2 and p38 MAP kinase signaling pathways, and induces COX-2
      expression, which is responsible for the sequential PGE2 biosynthesis and
      release, and furthermore, mediates the increase in BMP-2 expression at the
      transcriptional level. 

PMID- 24561082
TI  - Cytotoxic CD8+ T cells stimulate hematopoietic progenitors by promoting cytokine
      release from bone marrow mesenchymal stromal cells.
AB  - Cytotoxic CD8(+) T cells (CTLs) play a major role in host defense against
      intracellular pathogens, but a complete clearance of pathogens and return to
      homeostasis requires the regulated interplay of the innate and acquired immune
      systems. Here, we show that interferon gamma (IFNgamma) secreted by effector CTLs
      stimulates hematopoiesis at the level of early multipotent hematopoietic
      progenitor cells and induces myeloid differentiation. IFNgamma did not primarily
      affect hematopoietic stem or progenitor cells directly. Instead, it promoted the
      release of hematopoietic cytokines, including interleukin 6 from bone marrow
      mesenchymal stromal cells (MSCs) in the hematopoietic stem cell niche, which in
      turn reduced the expression of the transcription factors Runx-1 and Cebpalpha in
      early hematopoietic progenitor cells and increased myeloid differentiation.
      Therefore, our study indicates that, during an acute viral infection, CTLs
      indirectly modulate early multipotent hematopoietic progenitors via MSCs in order
      to trigger the temporary activation of emergency myelopoiesis and promote
      clearance of the infection.

PMID- 24561083
TI  - Axonal control of the adult neural stem cell niche.
AB  - The ventricular-subventricular zone (V-SVZ) is an extensive germinal niche
      containing neural stem cells (NSCs) in the walls of the lateral ventricles of the
      adult brain. How the adult brain's neural activity influences the behavior of
      adult NSCs remains largely unknown. We show that serotonergic (5HT) axons
      originating from a small group of neurons in the raphe form an extensive plexus
      on most of the ventricular walls. Electron microscopy revealed intimate contacts
      between 5HT axons and NSCs (B1) or ependymal cells (E1) and these cells were
      labeled by a transsynaptic viral tracer injected into the raphe. B1 cells express
      the 5HT receptors 2C and 5A. Electrophysiology showed that activation of these
      receptors in B1 cells induced small inward currents. Intraventricular infusion of
      5HT2C agonist or antagonist increased or decreased V-SVZ proliferation,
      respectively. These results indicate that supraependymal 5HT axons directly
      interact with NSCs to regulate neurogenesis via 5HT2C. 

PMID- 24561085
TI  - Fas, FasL, and cleaved caspases 8 and 3 in glioblastomas: a tissue microarray
      based study.
AB  - This investigation analyzed the immunoexpression of FasL, Fas, cleaved caspase-8,
      and cleaved caspase-3 in glioblastomas. Formalin-fixed and paraffin-embedded
      glioblastoma tissues and control brain tissues from 97 patients were analyzed by
      tissue microarrays and immunohistochemistry. Patients with glioblastomas that
      were negative or weakly stained (<50% of cells positive) for cleaved caspase-8
      had worse cancer-specific overall survival (median=8.5 months) than did patients
      with tumors that highly expressed cleaved caspase-8 (median=11.7 months;
      P=0.0325), independent of clinical variables. There was no association of other
      markers with survival, treatment, sex, age, tumor size, and primary site. Among
      the tumors, there were reasonable to good positive correlations between the
      expression of FasL and Fas (r=0.47) and between Fas and cleaved caspase-8
      (r=0.41), and there were poor positive correlations between Fas and cleaved
      caspase-3 (r=0.26), FasL and cleaved caspase-8 (r=0.22), and cleaved caspase-8
      and -3 (r=0.31). Our results suggest that Fas-Fas-ligand signal transduction
      could be inhibited, especially at the stage of caspase-8 activation, thereby
      establishing a major mechanism for evasion of apoptosis by these tumors. The
      absence or low expression of cleaved caspase-8 in the tumors was a negative
      prognostic indicator for patient survival. 

PMID- 24561086
TI  - [Immune depression after spontaneous subarachnoid hemorrhage].

PMID- 24561084
TI  - Conversion of danger signals into cytokine signals by hematopoietic stem and
      progenitor cells for regulation of stress-induced hematopoiesis.
AB  - During an infection, the body increases the output of mature immune cells in
      order to fight off the pathogen. Despite convincing evidence that hematopoietic
      stem and progenitor cells (HSPCs) can sense pathogens directly, how this
      contributes to hematopoietic cell output remains unknown. Here, we have combined
      mouse models with a single-cell proteomics platform to show that, in response to
      Toll-like receptor stimulation, short-term HSCs and multipotent progenitor cells
      produce copious amounts of diverse cytokines through nuclear factor kappaB (NF
      kappaB) signaling. Interestingly, the cytokine production ability of HSPCs trumps
      mature immune cells in both magnitude and breadth. Among cytokines produced by
      HSPCs, IL-6 is a particularly important regulator of myeloid differentiation and
      HSPC proliferation in a paracrine manner and in mediating rapid myeloid cell
      recovery during neutropenia. This study has uncovered an important property of
      HSPCs that enables them to convert danger signals into versatile cytokine signals
      for the regulation of stress hematopoiesis.

PMID- 24561087
TI  - Regional oxygen saturation index (rSO2) in brachioradialis and deltoid muscle.
      Correlation and prognosis in patients with respiratory sepsis.
AB  - OBJECTIVE: To compare oxygen saturation index (rSO2) obtained simultaneously in
      two different brachial muscles. DESIGN: Prospective and observational study.
      SETTING: Intensive care unit. PATIENTS: Critically ill patients with community
      acquired pneumonia. INTERVENTIONS: Two probes of NIRS device (INVOS 5100) were
      simultaneously placed on the brachioradialis (BR) and deltoid (D) muscles.
      VARIABLES: rSO2 measurements were recorded at baseline (ICU admission) and at
      24h. Demographic and clinical variables were registered. Pearson's correlation
      coefficient was used to assess the association between continuous variables. The
      consistency of the correlation was assessed using the intraclass correlation
      coefficient (ICC) and Bland-Altman plot. The predictive value of the rSO2 for
      mortality was calculated by ROC curve. RESULTS: Nineteen patients were included
      with an ICU mortality of 21.1%. The rSO2 values at baseline and at 24h were
      significantly higher in D than in BR muscle. Values obtained simultaneously in
      both limbs showed a strong correlation and adequate consistency: BR (r=0.95;
      p<0.001; ICC=0.94; 95% CI: 0.90-0.96; p<0.001), D (r=0.88; p=0.01; ICC=0.88; 95%
      CI: 0.80-0.90; p>0.001) but a wide limit of agreement. Non-survivors had rSO2
      values significantly lower than survivors at all times of the study. No patient
      with rSO2 >60% in BR died, and only 17.6% died with an rSO2 value >60% in D. Both
      muscles showed consistent discriminatory power for mortality. CONCLUSION: Both BR
      and D muscles were appropriate for measuring rSO2.

PMID- 24561088
TI  - Quantitative assessment of the nociceptive withdrawal reflex in healthy, non
      medicated experimental sheep.
AB  - This study aimed to characterize the nociceptive withdrawal reflex (NWR) and to
      define the nociceptive threshold in 25 healthy, non-medicated experimental sheep
      in standing posture. Electrical stimulation of the dorsal lateral digital nerves
      of the right thoracic and the pelvic limb was performed and surface
      electromyography (EMG) from the deltoid (all animals) and the femoral biceps (18
      animals) or the peroneus tertius muscles (7 animals) was recorded. The
      behavioural reaction following each stimulation was scored on a scale from 0 (no
      reaction) to 5 (strong whole body reaction). A train-of-five 1ms constant-current
      pulse was used and current intensity was stepwise increased until NWR threshold
      intensity was reached. The NWR threshold intensity (It) was defined as the
      minimal stimulus intensity able to evoke a reflex with a minimal Root-Mean-Square
      amplitude (RMSA) of 20MUV, a minimal duration of 10ms and a minimal reaction
      score of 1 (slight muscle contraction of the stimulated limb) within the time
      window of 20 to 130ms post-stimulation. Based on this value, further stimulations
      were performed below (0.9It) and above threshold (1.5It and 2It). The stimulus
      response curve was described. Data are reported as medians and interquartile
      ranges. At the deltoid muscle It was 4.4mA (2.9-5.7) with an RMSA of 62MUV (30
      102). At the biceps femoris muscle It was 7.0mA (4.0-10.0) with an RMSA of 43MUV
      (34-50) and at the peroneus tertius muscle It was 3.4mA (3.1-4.4) with an RMSA of
      38MUV (32-46). Above threshold, RMSA was significantly increased at all muscles.
      Below threshold, RMSA was only significantly smaller than at It for the peroneus
      tertius muscle but not for the other muscles. Data achieved in this study serve
      as reference for experimental or clinical applications of the conscious sheep
      model. 

PMID- 24561089
TI  - Resveratrol attenuates morphine antinociceptive tolerance via SIRT1 regulation in
      the rat spinal cord.
AB  - In recent years, researchers have begun to pay more attention to the role of
      Sirtuin 1 (SIRT1, a class III histone deacetylase) in pain. However, little
      research has been conducted examining the involvement of SIRT1 in chronic
      morphine tolerance. The aim of this study was to investigate the role of spinal
      SIRT1 and acetyl-histone H3(Ac-H3) in chronic morphine tolerance in rats. Chronic
      morphine tolerance was induced by twice-daily intrathecal (i.t.) injections of
      morphine (10MUg) for 6 days. Control rats received normal saline (NS).
      Resveratrol (Res, a SIRT1 stimulant, 30MUg i.t.) or dimethyl sulfoxide (DMSO,
      10MUl i.t.) was then injected on days 7-13. The thermal paw withdrawal threshold
      was assessed to determine the analgesic effects of morphine (10MUg). qRT-PCR,
      western blotting and immunohistochemistry were used to detect the expression of
      SIRT1 and global Ac-H3. Administration of morphine for 6 days induced a
      stabilized antinociceptive tolerance, down-regulated SIRT1 expression and up
      regulated Ac-H3 expression in the spinal dorsal horn. Resveratrol treatment from
      day 7 to 13 increased SIRT1 expression, suppressed global Ac-H3 expression
      compared to the morphine tolerance (MT) group, and significantly reversed
      morphine antinociceptive tolerance. These results suggest that resveratrol
      reversed morphine tolerance by upregulating the expression of SIRT1 in the spinal
      dorsal horn. SIRT1 and global Ac-H3 in the spinal cord may play an important role
      in the mechanisms of chronic morphine tolerance. 

PMID- 24561090
TI  - A functional polymorphism of the GTP cyclohydrolase 1 gene predicts attention
      performance.
AB  - Guanosine triphosphate cyclohydrolase 1 (GCH1) is the rate-limiting enzyme for
      the biosynthesis of tetrahydrobiopterin, a cofactor for aromatic amino acid
      hydroxylases and nitric oxide synthases. As monoamine neurotransmitters are
      synthesized by the reactions catalyzed by tyrosine hydroxylase and tryptophan
      hydroxylase, alterations in the content of tetrahydrobiopterin affect the
      monoamine levels in the brain. Here, we examined the possible association of a
      functional single-nucleotide polymorphism (SNP) of the GCH1 gene, rs841 (C+243T),
      with attentional function as assessed by the Continuous Performance Test
      Identical Pairs version (CPT-IP) in healthy individuals. We found that homozygous
      T/T genotype carriers of rs841 scored lower performance on the CPT-IP test. Our
      data suggest that alterations in GCH1 activity affect attentional function,
      especially sustained attention and vigilance. 

PMID- 24561091
TI  - Role of the 5-HT(7) receptor in the effects of intrathecal nefopam in neuropathic
      pain in rats.
AB  - Nefopam is a non-opioid analgesic drug, used widely in European countries to
      control postoperative pain. However, its mechanism of action remains unclear. In
      this study, the effects of intrathecal nefopam on spinal nerve-ligated induced
      neuropathic pain in rats were examined and the involvement of the 5-HT7 receptor
      at the spinal level was determined. Next, a 5-HT7 receptor antagonist (SB-269970)
      or descending serotonergic pathway ablation agent (5,7-DHT) was administered
      intrathecally before delivery of the nefopam to determine the contribution of
      spinal 5-HT7 receptors or descending serotonergic pathway to the activity of
      nefopam. The concentrations of 5-HT were measured. Intrathecal nefopam dose
      dependently produced the antiallodynic effect. Pre-treatment with intrathecal SB
      269970 reversed the antiallodynic effect of the nefopam. 5,7-DHT failed to affect
      the effect of nefopam. The concentrations of 5-HT in the spinal cord and plasma
      were decreased in neuropathic pain. Intrathecal nefopam increased the levels of 5
      HT in the spinal cord and plasma. Intrathecal nefopam is effective in the
      attenuation of neuropathic pain induced by spinal nerve ligation and nefopam
      increases the level of 5-HT. Additionally, the 5-HT7 receptor is involved in the
      antiallodynic action of nefopam in the spinal cord. 

PMID- 24561092
TI  - Extracellular matrix components mark the territories of circumventricular organs.
AB  - In the central nervous system the extracellular matrix has important roles, e.g.
      supporting the extracellular space, controlling the tissue hydration, binding
      soluble factors and influencing their diffusion. The distribution of the
      extracellular matrix components in the brain has been mapped but data on the
      circumventricular organs (CVOs) is not available yet. The CVOs lack the blood
      brain barrier and have relatively large perivascular spaces. The present study
      investigates tenascin-R and the lecticans: aggrecan, brevican, neurocan, and
      versican in the median eminence, the area postrema, the vascular organ of the
      lamina terminalis, the subfornical organ, the pineal body and the subcommissural
      organ of the rat applying immunohistochemical methods, and lectin histochemistry,
      using Wisteria floribunda agglutinin (WFA). The extracellular matrix components
      were found intensely expressed in the CVOs with two exceptions: aggrecan
      immunoreactivity visualized only neurons in the arcuate nucleus, and the
      subcommissural organ was not labeled with either WFA, or lecticans, or tenascin
      R. The different labelings usually overlapped each other. The distribution of the
      extracellular matrix components marked the territories of the CVOs. Considering
      these we suppose that the extracellular matrix is essential in the maintenance of
      CVO functions providing the large extracellular space which is required for
      diffusion and other processes important in their chemosensitive and
      neurosecretory activities. The decrease of extracellular matrix beyond the border
      of the organs may contribute to the control of the diffusion of molecules from
      the CVOs into the surrounding brain substance. 

PMID- 24561093
TI  - The trace amine associated receptor 1 agonist RO5263397 attenuates the induction
      of cocaine behavioral sensitization in rats.
AB  - The trace amine associated receptor (TAAR) 1 is a new G protein coupled receptor
      that critically modulates central dopaminergic system. Recently, several
      selective TAAR 1 ligands have been described to possess antipsychotic and
      antidepressant-like activities. However, it is unknown of the role of these
      ligands in modulating psychostimulant-induced neurobehavioral plasticity. This
      study examined the effects of a selective TAAR 1 agonist, RO5263397, on cocaine
      induced behavioral sensitization in rats, a rodent model of drug-induced
      behavioral plasticity. Daily treatment with 15mg/kg cocaine (i.p., 7 days)
      induced robust locomotor sensitization in rats. RO5263397 (1-10mg/kg, i.p.) alone
      did not significantly alter the locomotor activity. Acute treatment with
      RO5263397 (3.2 and 10mg/kg) did not significantly modify cocaine-induced
      hyperactivity; however, the induction of locomotor sensitization was
      significantly blocked after 7 days of daily RO5263397 treatment. More
      importantly, the expression of locomotor sensitization remained significantly
      attenuated when rats were re-tested 7 days after the last drug treatment. The
      marked attenuation of cocaine sensitization was also evidenced by the suppression
      of the dose-effect function (3.2-32mg/kg) of cocaine sensitization. Together,
      these data represent the first to report a critical modulatory role of TAAR 1
      agonists in cocaine-induced behavioral plasticity, which may be indicative of its
      potential role for altering other long-lasting behavioral maladaptations of
      cocaine including drug addiction. 

PMID- 24561094
TI  - Secretion of BDNF and GDNF from free and encapsulated choroid plexus epithelial
      cells.
AB  - Choroid plexus epithelial cells secrete numerous biologically active neurotrophic
      factors, which may be beneficial to the transplantation site. Encapsulated cells
      are often used in tissue transplantation. The present study was conducted to
      investigate the effect of encapsulation on the secretory function of choroid
      plexus epithelial cells. Neonatal rat choroid plexus epithelial cells were
      primarily cultured. After 9 days of culture, the cells were distributed into two
      groups, and one group of cells was encapsulated in vitro. The initial culture
      conditions such as cell numbers and medium volumes were the same. Supernatants in
      the free and encapsulated choroid plexus epithelial cells were collected at the
      time points of day 1 through day 7. Quantitative determination of the BDNF and
      GDNF levels was performed by enzyme-linked immunosorbent assay to assess the
      secretory function of the cells in the two forms. Statistical analyses were
      performed using a Student t test. P<0.05 was set to indicate statistical
      significance. A very similar secretion pattern was observed in both groups. In
      the first 4 days of encapsulation, the release of BDNF and GDNF in the
      encapsulated cells was significantly lower than that in the free cells, while the
      difference diminished after day 5. This in vitro study demonstrates that the
      secretion of BDNF and GDNF in encapsulated choroid plexus epithelial cells is
      different from that in non-encapsulated cells in the early stage of encapsulation
      treatment, whereas it is similar in the later stage. 

PMID- 24561096
TI  - Wavelength dependence of the fluorescence emission under conditions of open and
      closed Photosystem II reaction centres in the green alga Chlorella sorokiniana.
AB  - The fluorescence emission characteristics of the photosynthetic apparatus under
      conditions of open (F0) and closed (FM) Photosystem II reaction centres have been
      investigated under steady state conditions and by monitoring the decay lifetimes
      of the excited state, in vivo, in the green alga Chlorella sorokiniana. The
      results indicate a marked wavelength dependence of the ratio of the variable
      fluorescence, FV=FM-F0, over FM, a parameter that is often employed to estimate
      the maximal quantum efficiency of Photosystem II. The maximal value of the FV/FM
      ratio is observed between 660 and 680nm and the minimal in the 690-730nm region.
      It is possible to attribute the spectral variation of FV/FM principally to the
      contribution of Photosystem I fluorescence emission at room temperature.
      Moreover, the analysis of the excited state lifetime at F0 and FM indicates only
      a small wavelength dependence of Photosystem II trapping efficiency in vivo. 

PMID- 24561095
TI  - Novel RYR1 missense mutations in six Chinese patients with central core disease.
AB  - Central core disease (CCD) is a genetically heterogeneous congenital myopathy,
      and ryanodine receptor 1 (RYR1, gene ID6261) is the only pathogenicity gene until
      now. Data on mutation characteristics of RYR1 in the Chinese CCD population are
      scarce. This study searched for mutations in the C-terminal-encoding domain of
      RYR1 in six Chinese patients with CCD, and identified five missense mutations
      (N4807F, R4861H, R4893P, G4897D, and I4898T). Among them, N4807F, G4897D were
      novel while R4861H, R4893P, and I4898T were previously reported. All missense
      mutations were highly conserved across the species of human, mouse, rabbit, fish,
      and pig. This study found that mutations could be identified in about 85% CCD
      patients, even if only the C-terminal-encoding region of RYR1 was screened. Many
      mutations clustered in exons 100-102. 

PMID- 24561097
TI  - An octogenarian with dysphagia and weight loss.

PMID- 24561098
TI  - Phlebosclerotic colitis presenting as intestinal obstruction.

PMID- 24561100
TI  - Respiratory sinus arrhythmia responses to cognitive tasks: effects of task
      factors and RSA indices.
AB  - Many studies show that respiratory sinus arrhythmia (RSA) decreases while
      performing cognitive tasks. However, there is uncertainty about the role of
      contaminating factors such as physical activity and stress-inducing task
      variables. Different methods to quantify RSA may also contribute to variable
      results. In 83 healthy subjects, we studied RSA responses to a working memory
      task requiring varying levels of cognitive control and a perceptual attention
      task not requiring strong cognitive control. RSA responses were quantified in the
      time and frequency domain and were additionally corrected for differences in mean
      interbeat interval and respiration rate, resulting in eight different RSA
      indices. The two tasks were clearly differentiated by heart rate and facial EMG
      reference measures. Cognitive control induced inhibition of RSA whereas
      perceptual attention generally did not. However, the results show several
      differences between different RSA indices, emphasizing the importance of
      methodological variables. Age and sex did not influence the results. 

PMID- 24561099
TI  - Brain, body, and cognition: neural, physiological and self-report correlates of
      phobic and normative fear.
AB  - The phobic fear response appears to resemble an intense form of normal threat
      responding that can be induced in a nonthreatening situation. However, normative
      and phobic fear are rarely contrasted directly, thus the degree to which these
      two types of fear elicit similar neural and bodily responses is not well
      understood. To examine biological correlates of normal and phobic fear, 21 snake
      phobic and 21 nonphobic controls saw videos of slithering snakes, attacking
      snakes and fish in an event-related fMRI design. Simultaneous eletrodermal,
      pupillary, and self-reported affective responses were collected. Nonphobic fear
      activated a network of threat-responsive brain regions and involved pupillary
      dilation, electrodermal response and self-reported affect selective to the
      attacking snakes. Phobic fear recruited a large array of brain regions including
      those active in normal fear plus additional structures and also engendered
      increased pupil dilation, electrodermal and self-reported responses that were
      greater to any snake versus fish. Importantly, phobics showed greater between-
      and within-subject concordance among neural, electrodermal, pupillary, and
      subjective report measures. These results suggest phobic responses recruit
      overlapping but more strongly activated and more extensive networks of brain
      activity as compared to normative fear, and are characterized by greater
      concordance among neural activation, peripheral physiology and self-report. It is
      yet unclear whether concordance is unique to psychopathology, or rather simply an
      indicator of the intense fear seen in the phobic response, but these results
      underscore the importance of synchrony between brain, body, and cognition during
      the phobic reaction. 

PMID- 24561101
TI  - Is stress perceived differently in relationships with parents and peers? Inter-
      and intra-regional comparisons on adolescents from 21 nations.
AB  - This study investigated how adolescents (mean age of 15 years) from 21 countries
      perceived parent- and peer-related stress. Across countries, adolescents
      perceived parent-related stress at considerably greater levels than peer-related
      stress. Adolescents assigned to six geographical regions differed significantly
      in overall stress levels as well as in the disparity between perceived stress
      levels in the parent and peer domain. Regional comparisons revealed that
      adolescents from Southern Europe exhibited the highest levels of parent-related
      stress, followed by adolescents from Latin America, the Middle East, and Asia.
      The stress levels of adolescents from Central European and North American
      countries were generally quite low. Correspondence analyses revealed distinctive
      patterns of perceived stress in close relationships, depending on the region. The
      discussion focuses on different parental styles and cultural values as potential
      influential factors for differences in stress perception between regions. 

PMID- 24561102
TI  - Transcriptional response of immune genes in gills and the interbranchial lymphoid
      tissue of Atlantic salmon challenged with infectious salmon anaemia virus.
AB  - Previously, it has been assumed that fish lack organized mucosa-associated
      lymphoid structures. Recently, an interbranchial lymphoid tissue (ILT) was
      described in salmonid gills at a site with substantial exposure to antigen. In
      this study, immune responses were examined in gills, mid-kidney and the laser
      dissected ILT of Atlantic salmon (Salmo salar L.) infected with infectious salmon
      anaemia virus (ISAV). A strong innate response was observed in gills and mid
      kidney and even in the laser-dissected ILT, despite the fact that no virus could
      be traced in this tissue. A small delayed increase in IgT transcripts,
      exclusively in the ILT, could indicate that this tissue has a role as a secondary
      lymphoid organ with clonal expansion of IgT expressing B-cells. Compared to the
      other examined tissues, gills displayed the earliest replication of the virus,
      further supporting this tissue as the main entry route for infection with ISAV. 

PMID- 24561103
TI  - CD2 and CD8alpha define porcine gammadelta T cells with distinct cytokine
      production profiles.
AB  - gammadelta T cells are a remarkably prominent T-cell subset in swine with a high
      prevalence in blood. Phenotypic analyses in this study showed that CD2(-)
      gammadelta T cells in their vast majority had a CD8alpha(-)SLA-DR(-)CD27(+)
      phenotype. CD2(+) gammadelta T cells dominated in spleen and lymph nodes and had
      a more heterogeneous phenotype. CD8alpha(+)SLA-DR(-)CD27(+) gammadelta T cells
      prevailed in blood, spleen and lymph nodes whereas in liver a CD8alpha(+)SLA
      DR(+)CD27(-) phenotype dominated, indicating an enrichment of terminally
      differentiated gammadelta T cells. gammadelta T cells were also investigated for
      their potential to produce IFN-gamma, TNF-alpha and IL-17A. Within CD2(+)
      gammadelta T cells, IFN-gamma and TNF-alpha single-producers as well as IFN
      gamma/TNF-alpha double-producers dominated, which had a CD8alpha(+)CD27(+/-)
      phenotype. IL-17A-producing gammadelta T cells were only found within CD2(-)
      gammadelta T cells, mostly co-produced TNF-alpha and had a rare CD8alpha(+)CD27(
      ) phenotype. However, quantitatively TNF-alpha single-producers strongly
      dominated within CD2(-) gammadelta T cells. In summary, our data identify CD2 and
      CD8alpha as important molecules correlating with functional differentiation. 

PMID- 24561104
TI  - On the shape of the Task Group 43 anisotropy factor for linear brachytherapy
      sources at short distances.
AB  - PURPOSE: To investigate the peak shown by the American Association of Physicists
      in Medicine (AAPM) Task Group 43 1D anisotropy function at short distances from
      the source. METHODS AND MATERIALS: The 1D anisotropy function of an ideal
      nonencapsulated photon linear source is calculated. A simple analytical model
      developed to evaluate the dose because of photon point-like sources has been
      applied. Previously, the model has been tested by comparing the values obtained
      for the various Task Group 43 dosimetric functions with those calculated with the
      Monte Carlo code PENELOPE for three different photon energies. RESULTS: The model
      is able to reproduce the behavior of the 1D anisotropy function, describing the
      maximum that appears at a distance between 1 and 2 mm from the source. The reason
      for this behavior has been identified in terms of the contributions of the source
      activity inside and outside the scoring sphere. CONCLUSIONS: Although it is not
      usually shown in reference data, this behavior should be taken into account for
      accurate dosimetric calculations.

PMID- 24561106
TI  - A survey of anesthesiologist and anesthetist attitudes toward single-use vials in
      an academic medical center.
AB  - STUDY OBJECTIVE: To evaluate whether proper implementation of safety measures was
      uniform at 5 hospitals, and to elucidate motivating factors that lead to
      nonadherence. DESIGN: Electronic anonymous survey instrument. SETTING: Academic
      medical center. MEASUREMENTS: Of the 319 surveys sent to anesthesia providers
      across 5 hospitals, 89 responses were obtained. Questions addressed compliance
      with Centers of Disease Control (CDC) safety standards and the rationale for
      anesthesia providers' decisions to comply or not comply with these standards.
      MAIN RESULTS: 59.6% of respondents reported that they had reused vials between
      cases, while 40.4% had never done so. Of the 89 respondents, 63 (44%) felt that
      cost was the primary factor that prevented them from using entirely new
      medications on each case. Thirty-two (23%) reported convenience/efficiency as the
      reason; 11 (8%) responded that time prevented them from using entirely new
      medications on each case; 14 (10%) reported that the environment was a driving
      factor; and 3 individuals (2%) responded apathy. Eighteen (13%) responded "other"
      and, when asked to amplify a response, most of these individuals reported that
      they do use entirely new medications on each case. CONCLUSIONS: Safe anesthetic
      practices were not uniform among respondents, and one of the main reasons given
      for noncompliance with safe standards was cost.

PMID- 24561107
TI  - Supraglotic pulsatile jet oxygenation and ventilation during deep propofol
      sedation for upper gastrointestinal endoscopy in a morbidly obese patient.

PMID- 24561105
TI  - Ultrasound artifacts mimicking pleural sliding after pneumonectomy.
AB  - STUDY OBJECTIVE: To determine the presence of pleural sliding on chest
      ultrasonography (US) in a series of patients admitted to a surgical intensive
      care unit (SICU). DESIGN: Prospective, observational study. SETTING: 16-bed SICU
      of a University hospital. PATIENTS: 8 patients (7 men, 1 woman), aged 64 - 73
      years (mean 67.5 yrs). Seven patients underwent pneumonectomy for pulmonary
      neoplasms; one patient underwent an atypical lung resection after having
      undergone a pneumonectomy one year before. INTERVENTIONS: None. MEASUREMENTS:
      Chest ultrasounds were performed during mechanical ventilation and spontaneous
      ventilation after endotracheal tube removal. In both examinations, pleural
      sliding was searched bilaterally in brightness mode (B-mode) and motion mode (M
      mode) on the anterior thoracic wall in the least gravitationally dependent areas.
      RESULTS: During mechanical ventilation, pleural sliding was always absent on the
      side of the pneumonectomy and present on the other side. During spontaneous
      ventilation, some artifacts mimicking pleural sliding were noted on the side of
      the pneumonectomy both in B-mode and M-mode (presence of the seashore sign) in
      all patients, except for the one patient who had undergone a pneumonectomy one
      year earlier. Those artifacts became more pronounced during deep breaths.
      CONCLUSIONS: Ultrasound artifacts mimicking pleural sliding may be observed in
      the absence of the lung and may originate from the activity of intercostal
      muscles since they become more evident during deep breathing.

PMID- 24561108
TI  - Cerebral venous thrombosis complicating severe preeclampsia in the postpartum
      period: a diagnostic challenge.
AB  - A 26 year old primigravida with preeclampsia was diagnosed with a cerebral venous
      thrombosis 6 days following Cesarean section. The diagnosis was initially
      challenging due to the patient's history of migraines, the preeclampsia, multiple
      attempts at spinal anesthesia for Cesarean section, and a dural puncture while
      performing epidural blood patch. 

PMID- 24561109
TI  - Cancer-associated fibroblasts: recent developments and emerging challenges.

PMID- 24561110
TI  - Sonochemistry in the service of SOFC research.
AB  - Decoration of SOFC anode cermets with metal nanoparticles (NPs) enchance their
      ability and stability in natural gas to hydrogen reform. A novel
      sonoelectrochemical approach of Au-NPs synthesis (mean 12.31+/-2.69nm) is
      suggested, according to which the sonication is held constant while the
      electrochemical activity is either pulsed or continuous. The gold colloidal
      solution is cosonicated with state of the art cermet powder to yield particles
      decorated with Au-NPs. Nevertheless sonochemical routes of mixed molybdenum,
      rhenium or tungsten mixed oxides synthesis are utilized in order to decorate SOFC
      anode cermets. The decoration loading achieved spanned from 0.1 to 10.0wt.%. 

PMID- 24561111
TI  - Coronary artery disease in patients with heart failure: incidental, coincidental,
      or a target for therapy?

PMID- 24561112
TI  - Venous thromboembolism in older adults: A community-based study.
AB  - BACKGROUND: While the incidence of venous thromboembolism increases with age,
      little is known about its contemporary management or outcomes in older patients.
      Our goal was to compare the characteristics, treatment, and outcomes associated
      with venous thromboembolism, in patients aged 65-69 years, 70-74 years, 75-79
      years, and 80+ years. METHODS/PARTICIPANTS: We prospectively followed 542
      subjects aged >=65 years with venous thromboembolism from January 2008 through
      August 2011 at 6 sites. In addition, a retrospective study of 681 additional
      subjects aged >=65 years with venous thromboembolism diagnosed in 2007 and 2009
      was conducted at the same 6 sites. RESULTS: With advancing age, patients were
      more likely to suffer provoked venous thromboembolism but less likely to present
      with pulmonary embolism. Patients with unprovoked, provoked, or malignancy
      associated venous thromboembolism received warfarin for a median of 401 days, 203
      days, and 529 days, respectively. Age >=80 years was not associated with an
      increased risk of recurrent venous thromboembolism, but there was an increased
      risk of all-cause mortality. CONCLUSION: With advancing age, patients are more
      likely to suffer hospital-associated and provoked venous thromboembolism. Many
      elderly patients with provoked or unprovoked venous thromboembolism were treated
      for >3 months or >12 months, respectively. Given that advanced age was not
      associated with increased risk of recurrent venous thromboembolism, but elderly
      patients in general have a higher risk of bleeding from continued anticoagulant
      therapy, such practice is potentially harmful. At the same time, such an argument
      could be used to more vigorously offer prophylaxis in the first place.

PMID- 24561113
TI  - Beta-blocker use in ST-segment elevation myocardial infarction in the reperfusion
      era (GRACE).
AB  - BACKGROUND: Current guidelines recommend early oral beta-blocker administration
      in the management of acute coronary syndromes for patients who are not at high
      risk of complications. METHODS: Data from patients enrolled between 2000 and 2007
      in the Global Registry of Acute Coronary Events (GRACE) were used to evaluate
      hospital outcomes in 3 cohorts of patients admitted with ST-elevation myocardial
      infarction, based on beta-blocker use (early [first 24 hours] intravenous (IV)
      [+/- oral], only early oral, or delayed [after first 24 hours]). RESULTS: Among
      13,110 patients with ST-elevation myocardial infarction, 21% received any early
      IV beta-blockers, 65% received only early oral beta-blockers, and 14% received
      delayed (>24 hours) beta-blockers. Higher systolic blood pressure, higher heart
      rate, and chronic beta-blocker use were independent predictors of early beta
      blocker use. Early beta-blocker use was less likely in older patients, patients
      with moderate to severe left ventricular dysfunction, and in those presenting
      with inferior myocardial infarction or Killip class II or III heart failure. IV
      beta-blocker use and delayed beta-blocker use were associated with higher rates
      of cardiogenic shock, sustained ventricular fibrillation/ventricular tachycardia,
      and acute heart failure, compared with oral beta-blocker use. In-hospital
      mortality was increased with IV beta-blocker use (propensity score adjusted odds
      ratio, 1.41; 95% confidence interval, 1.03-1.92) but significantly reduced with
      delayed beta-blocker administration (propensity adjusted odds ratio, 0.44; 95%
      confidence interval, 0.26-0.74). CONCLUSIONS: Early beta-blocker use is common in
      patients presenting with ST-elevation myocardial infarction, with oral
      administration being the most prevalent. Oral beta-blockers were associated with
      a decrease in the risk of cardiogenic shock, ventricular arrhythmias, and acute
      heart failure. However, the early receipt of any form of beta-blockers was
      associated with an increase in hospital mortality.

PMID- 24561115
TI  - Validation of rebound tonometry for intraocular pressure measurement in the
      rabbit.
AB  - Rabbits play a growing role in research into glaucoma surgical models and ocular
      drug delivery models. However, the lack of an accurate method for measuring
      intraocular pressure (IOP) in this animal has been a significant deficit. In this
      study we validated the use of the TonoVet rebound tonometer and provide
      conversion tables for its use in rabbits. Experiments were performed on 18 adult
      New Zealand White rabbits. The TonoVet measurements were obtained and compared to
      manometric readings by anterior chamber (AC) cannulation. The TonoVet position
      and 'd' (dog or cat) and 'p' (other species) modes were compared. The sensitivity
      of the TonoVet tonometer in assessing IOP changes was also tested. There was a
      strong linear correlation for both the 'd' mode (mean slope = 0.84 +/- 0.03, r(2)
      = 0.99 +/- 0.03) and the 'p' mode (mean slope = 0.64 +/- 0.02, r2 = 0.97 +/-
      0.01) of the TonoVet with manometric IOP. However, the TonoVet had a tendency to
      underestimate IOP compared to manometry and conversion formulae were possible to
      calculate for both modes. The orientation of the TonoVet handle had no effect on
      IOP reading, as long as the groove was horizontal. No significant differences
      were observed when comparing right and left eyes (P > 0.05). IOP recovered four
      days after cannulation. Younger rabbits had lower IOP compared with older rabbits
      (P < 0.01). Timolol produced a 2.5 mmHg reduction in IOP 2 h later as detected by
      the TonoVet. Using the conversion table presented, the TonoVet is a reliable and
      precise tool for the measurement of IOP in rabbits.

PMID- 24561114
TI  - Muscle mass index as a predictor of longevity in older adults.
AB  - OBJECTIVE: Obesity (as defined by body mass index) has not been associated
      consistently with higher mortality in older adults. However, total body mass
      includes fat and muscle, which have different metabolic effects. This study was
      designed to test the hypothesis that greater muscle mass in older adults is
      associated with lower all-cause mortality. METHODS: All-cause mortality was
      analyzed by the year 2004 in 3659 participants from the National Health and
      Nutrition Examination Survey III who were aged 55 years or more (65 years if
      women) at the time of the survey (1988-1994). Individuals who were underweight or
      died in the first 2 years of follow-up were excluded to remove frail elders from
      the sample. Skeletal muscle mass was measured using bioelectrical impedance, and
      muscle mass index was defined as muscle mass divided by height squared. Modified
      Poisson regression and proportional hazards regression were used to examine the
      relationship of muscle mass index with all-cause mortality risk and rate,
      respectively, adjusted for central obesity (waist hip ratio) and other
      significant covariates. RESULTS: In adjusted analyses, total mortality was
      significantly lower in the fourth quartile of muscle mass index compared with the
      first quartile: adjusted risk ratio 0.81 (95% confidence interval, 0.71-0.91) and
      adjusted hazard ratio 0.80 (95% confidence interval, 0.66-0.97). CONCLUSIONS:
      This study demonstrates the survival predication ability of relative muscle mass
      and highlights the need to look beyond total body mass in assessing the health of
      older adults.

PMID- 24561116
TI  - Molecular epidemiology of Aleutian mink disease virus in China.
AB  - Aleutian mink disease (mink plasmacytosis) is a very severe immune-complex
      mediated disease affecting minks. It is caused by the Aleutian mink disease virus
      (AMDV). To obtain a better understanding of the molecular epidemiology of AMDV in
      China, a total of 420 samples were collected from mink farms in five major mink
      farming provinces in China. After testing serum antibodies using
      counterimmunoelectrophoresis (CIEP), 23 of the 340 positive samples were randomly
      selected and analyzed. The full length of the major structural protein gene (VP2)
      from all the samples was amplified and sequenced. The sequences in the twenty
      three samples from 5 farms in 5 provinces were phylogenetically analyzed, and
      eleven were found to have homologous sequences in GenBank. A rooted phylogenetic
      tree was constructed using the unweighted pair-group method with arithmetic
      (UPGMA) method. Phylogenetic analysis showed that the AMDV strains formed five
      groups (I-VI), and four of them contained Chinese strains. The tree showed that
      the two AMVD lineages had been introduced to China independently. Over 70% of the
      Chinese isolates were classified into two groups, all of which contained Chinese
      strains. The results of the analysis suggested that the distribution of the AMDV
      strains was not based on geographical origin, and both indigenous AMDV and
      imported AMDV were prevalent in the primary mink production areas in China. 

PMID- 24561117
TI  - [Acute coronary syndrome in a nonagenarian; from the clinic to the evidence].

PMID- 24561118
TI  - LSD1 sustains pancreatic cancer growth via maintaining HIF1alpha-dependent
      glycolytic process.
AB  - The histone demethylase LSD1 (lysine specific demethylase 1) plays an important
      role in the epigenetic regulation of gene transcription. Our study investigated
      the role of LSD1 in pancreatic cancer and demonstrated that LSD1 was
      significantly up-regulated in pancreatic cancer patient tissue samples, and
      elevated LSD1 protein levels positively correlated with overall survival of
      pancreatic cancer patients. Using in vitro and in vivo models, we demonstrated
      that knock-down of LSD1 repressed proliferation and tumorigenicity of pancreatic
      cancer cells. Mechanistically, our study demonstrated that LSD1 synergized with
      HIF1alpha (hypoxia inducible factor-1alpha) in maintaining glycolytic process,
      which fueled pancreatic cancer uncontrolled proliferation. 

PMID- 24561119
TI  - Wnt inhibitory factor-1 functions as a tumor suppressor through modulating
      Wnt/beta-catenin signaling in neuroblastoma.
AB  - Neuroblastoma is the most common extracranial solid tumor in childhood and is
      associated with serious morbidity and mortality. The effective treatment of
      neuroblastoma remains one of the major challenges in pediatric oncology. The Wnt
      signaling pathway has been shown to play a significant role in the pathogenesis
      of adult and pediatric tumors. WIF-1 has been identified as an important Wnt
      antagonist which inhibits Wnt/beta-catenin signaling by directly binding to Wnt
      proteins. However, the expression and function of WIF-1 in neuroblastoma remains
      unknown. The present study showed that WIF-1 was downregulated with high level
      promoter methylation in neuroblastoma cells, and was significantly upregulated
      after exposure to demethylating agent. This finding suggests that downregulation
      of WIF-1 was associated with its promoter methylation in neuroblastoma. To
      further study the potential function of WIF-1 in neuroblastoma, we constructed a
      plasmid that over-expressed WIF-1 and transfected the plasmid into one
      neuroblastoma cell line SK-N-SH. We found that restoration of WIF-1 inhibited the
      growth and proliferation of neuroblastoma cells in vitro. Moreover, Wnt/beta
      catenin signaling activity and target genes expression were reduced by WIF-1
      restoration. These results provide support that WIF-1 is downregulated and
      functions as a tumor suppressor by antagonizing Wnt/beta-catenin signaling in
      neuroblastoma, suggesting a potential role as a therapeutic target in
      neuroblastoma.

PMID- 24561120
TI  - Poisoning by Brachiaria brizantha in flocks of naive and experienced sheep.
AB  - The aim of this work was to study the effects of protodioscin ingestion in two
      different flocks of sheep: a flock of 23 crossbreed Mato Grosso do Sul Native
      sheep raised on Brachiaria spp. pastures from birth (experienced flock) in the
      state of Mato Grosso do Sul; and another flock (naive flock) of 18 crossbred
      Dorper * Santa Ines sheep raised in the state of Parana in Paspalum notatum and
      Lolium multiflorum pastures. The two flocks grazed together in a Brachiaria
      brizantha pasture during a 140-day period in the rainy season. At the beginning
      of the experiment and every 14 days thereafter, blood samples were collected for
      determination of serum activities of gamma-glutamyl transferase (GGT) and
      aspartate aminotransferase (AST), and for determination of the icterus index. On
      the same days, samples of young, mature and old B. brizantha leaves were
      collected for protodioscin quantification. Naive sheep were more susceptible to
      poisoning by B. brizantha than experienced sheep. Six sheep in the naive flock
      were poisoned, and two of these died. Two sheep in the experienced flock were
      poisoned, and one of them died. The mean activities of serum GGT and AST were
      significantly higher in the naive flock, also evidencing a higher susceptibility
      to the poison. These results suggest that flocks of sheep include animals with
      different degrees of resistance to Brachiaria spp. poisoning and that culling the
      susceptible animals may considerably increase of the resistance of the flock. The
      clinical signs and the lesions were similar to those previously reported.
      However, in sheep with black coats, the main clinical sign was weight loss
      without photosensitization-mediated dermatitis. One sheep from the experienced
      flock presented cirrhosis, with clinical signs of exercise intolerance. The
      protodioscin concentration (% DM) ranged from 0.87% to 2.58% (mean +/- SD: 1.64
      +/- 0.58) in young leaves, 1.16%-2.53% (1.67 +/- 0.44) in mature leaves and 0.98%
      2.07% (1.52 +/- 0.37) in old leaves. A negative relationship was found between
      saponin concentration and total cumulative precipitation. 

PMID- 24561121
TI  - Jack bean (Canavalia ensiformis) urease induces eicosanoid-modulated hemocyte
      aggregation in the Chagas' disease vector Rhodnius prolixus.
AB  - Ureases are multifunctional proteins that display biological activities
      independently of their enzymatic function, such as induction of exocytosis and
      insecticidal effects. Rhodnius prolixus, a major vector of Chagas' disease, is a
      model for studies on the entomotoxicity of jack bean urease (JBU). We have
      previously shown that JBU induces the production of eicosanoids in isolated
      tissues of R. prolixus. In insects, the immune response comprises cellular and
      humoral reactions, and is centrally modulated by eicosanoids. Cyclooxygenase
      products signal immunity in insects, mainly cellular reactions, such as hemocyte
      aggregation. In searching for a link between JBU's toxic effects and immune
      reactions in insects, we have studied the effects of this toxin on R. prolixus
      hemocytes. JBU triggers aggregation of hemocytes after injection into the
      hemocoel and when applied to isolated cells. On in vitro assays, the eicosanoid
      synthesis inhibitors dexamethasone (phospholipase A2 indirect inhibitor) and
      indomethacin (cyclooxygenase inhibitor) counteracted JBU's effect, indicating
      that eicosanoids, more specifically cyclooxygenase products, are likely to
      mediate the aggregation response. Contrarily, the inhibitors esculetin and
      baicalein were inactive, suggesting that lipoxygenase products are not involved
      in JBU's effect. Extracellular calcium was also necessary for JBU's effect, in
      agreement to other cell models responsive to ureases. A progressive darkening of
      the medium of JBU-treated hemocytes was observed, suggestive of a humoral
      response. JBU was immunolocalized in the cultured cells upon treatment along with
      cytoskeleton damage. The highest concentration of JBU tested on cultured cells
      also led to nuclei aggregation of adherent hemocytes. This is the first time
      urease has been shown to affect insect hemocytes, contributing to our
      understanding of the entomotoxic mechanisms of action of this protein. 

PMID- 24561122
TI  - Spontaneous poisoning by Solanum subinerme Jack as a cause of cerebellar cortical
      degeneration in cattle.
AB  - The present work reports cerebellar degeneration in cattle associated with the
      ingestion of Solanum subinerme in northern Brazil. The main clinical signs were
      periodic crises with loss of balance, falls, opisthotonus, and nystagmus. The
      histological lesions consisted of diffuse vacuolation of the perikaryon of the
      Purkinje neurons, followed by the loss of these cells and their substitution by
      Bergman glia. It is concluded that S. subinerme is another species of Solanum
      that causes cerebellar degeneration in cattle. 

PMID- 24561123
TI  - CHIP-MYTH: a novel interactive proteomics method for the assessment of agonist
      dependent interactions of the human beta2-adrenergic receptor.
AB  - G-protein coupled receptors (GPCRs) are involved in a variety of disease
      processes and comprise major drug targets. However, the complexity of integral
      membrane proteins such as GPCRs makes the identification of their interacting
      partners and subsequent drug development challenging. A comprehensive
      understanding of GPCR protein interaction networks is needed to design effective
      therapeutic strategies to inhibit these drug targets. Here, we developed a novel
      split-ubiquitin membrane yeast two-hybrid (MYTH) technology called CHIP-MYTH,
      which allows the unbiased characterization of interaction partners of full-length
      GPCRs in a drug-dependent manner. This was achieved by coupling DNA microarray
      technology to the MYTH approach, which allows a quantitative evaluation of
      interacting partners of a given integral membrane protein in the presence or
      absence of drug. As a proof of principle, we applied the CHIP-MYTH approach to
      the human beta2-adrenergic receptor (beta2AR), a target of interest in the
      treatment of asthma, chronic obstructive pulmonary disease (COPD), neurological
      disease, cardiovascular disease, and obesity. A CHIP-MYTH screen was performed in
      the presence or absence of salmeterol, a long-acting beta2AR-agonist. Our results
      suggest that beta2AR activation with salmeterol can induce the dissociation of
      heterotrimeric G-proteins, Galphabetagamma, into Galpha and Gbetagamma subunits,
      which in turn activates downstream signaling cascades. Using CHIP-MYTH, we
      confirmed previously known and identified novel beta2AR interactors involved in
      GPCR-mediated signaling cascades. Several of these interactions were confirmed in
      mammalian cells using LUminescence-based Mammalian IntERactome (LUMIER) and co
      immunoprecipitation assays. In summary, the CHIP-MYTH approach is ideal for
      conducting comprehensive protein-protein interactions (PPI) screenings of full
      length GPCRs in the presence or absence of drugs, thus providing a valuable tool
      to further our understanding of GPCR-mediated signaling.

PMID- 24561124
TI  - CXCL12-induced upregulation of FOXM1 expression promotes human glioblastoma cell
      invasion.
AB  - Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor;
      it is highly aggressive and is associated with a poor prognosis. Binding of the
      chemokine CXCL12 to its receptors (CXCR4 and CXCR7) contributes to the activation
      of many downstream signaling pathways and promotes the invasion of various
      malignant tumor cells, including GBM cells. FOXM1, a transcription factor
      involved in cell cycle regulation, is overexpressed in GBM and is involved in GBM
      progression. However, the molecular mechanisms by which CXCL12 promotes the
      invasion of human GBM cells remain unclear. In this study, we demonstrate that
      CXCL12 increases the production of FOXM1 by binding to CXCR4 in GBM cell lines.
      Furthermore, pretreatment with an inhibitor of the PI3K/AKT pathway abrogated the
      CXCL12-induced expression of FOXM1. In addition, there was a positive correlation
      between CXCL12/CXCR4 expression and FOXM1 expression in human malignant glioma
      tissues. Finally, a functional assay revealed that CXCL12 does not stimulate GBM
      cell invasion when FOXM1 expression is silenced using a small interfering RNA
      (siRNA). Collectively, these findings suggest that CXCL12 promotes GBM cell
      invasion in part by increasing the expression of FOXM1, which is mediated in part
      by a PI3K/AKT-dependent mechanism in vitro.

PMID- 24561126
TI  - Iron bioavailability in larvae yellow snapper (Lutjanus argentiventris): cloning
      and expression analysis of ferritin-H.
AB  - Ferritin is a major intracellular iron storage protein in higher vertebrates and
      plays an important role in iron metabolism. In this study, ferritin H subunit was
      cloned from the larvae of yellow snapper, Lutjanus argentiventris, by rapid
      amplification of cDNA ends (RACE) following in silico transcriptome analysis. The
      full-length cDNAs of the LaFeH was 1231 bp in length encoding 177 amino acids
      with a predicted molecular mass (MW) about 20.82 kDa and theoretical isoelectric
      point (pI) of 5.79. Amino acid alignment revealed that LaFeH shared high
      similarity with other known ferritins. It shared high degree identity to the
      ferritin H subunits of Lates calcarifer (99%), Takifugu rubripes (97%) and
      Dicentrarchus labrax (97%), and low identity to that of human (82%) and mouse
      (84%). By real-time PCR assays, the mRNA transcripts of LaFeH was found to be
      higher expressed in head-kidney, eye, heart and brain. Moreover, mRNA expression
      levels of LaFeH was measured by real-time PCR in larvae exposed with graded
      levels of iron (6.8 MUg/ml and 13.6 MUg/ml (Fe2x and Fe4x, respectively) and an
      iron chelation assay. Results showed that the expression of the LaFeH mRNA
      increased gradually with Fe2x in water. The LaFeH gene expression declined with
      increasing iron exposure levels at Fe4x. Finally, we can observe a high
      expression of LaFeH gene in larvae exposed to iron chelation therapy at 2 h;
      however this increase was gradually decreasing over time. In summary, the LaFeH
      gene expression for larvae yellow snapper showed a dose-depend increase following
      the iron treatment. These data indicated that iron bioavailability regulates
      LaFeH at transcriptional level in larvae yellow snapper. Further studies are
      necessary to ascertain their role in the immune response in teleost fish. 

PMID- 24561127
TI  - Adaptive and innate immune molecules in developing rainbow trout, Oncorhynchus
      mykiss eggs and larvae: expression of genes and occurrence of effector molecules.
AB  - The ontogenetic development of the immune system was studied during the egg phase
      and the early post-hatch period of rainbow trout. Quantitative real-time PCR
      (qPCR) was used to assess the timing and degree of expression of 9 important
      immune relevant genes and EF1-alpha. Further, immunohistochemical staining using
      monoclonal antibodies was applied on rainbow trout embryos and larvae in order to
      localize five different protein molecules (MHCII, CD8, IgM, IgT and SAA) in the
      developing tissue and immune organs. Maternally transferred transcripts of EF1
      alpha mRNA were detected in the unfertilized egg. Early onset of expression was
      seen for all immune genes at very low levels. The amount of mRNA slowly increased
      and peaked around and after hatching. The highest increases were seen for MHCII,
      C3, C5 and SAA. Immunohistochemistry using five monoclonal antibodies showed
      positive staining from day 84 post fertilization. Skin, gills, intestine,
      pseudobranch and thymus showed reactivity for MHCII, thymus for CD8, gill mucus
      for IgT and pseudobranch and cartilage associated tissue for SAA. The importance
      of detected factors for early protection of eggs and larvae is discussed. 

PMID- 24561125
TI  - Reductions in systolic blood pressure with liraglutide in patients with type 2
      diabetes: insights from a patient-level pooled analysis of six randomized
      clinical trials.
AB  - AIMS: To quantify the effect of liraglutide on systolic blood pressure (SBP) and
      pulse in patients with type 2 diabetes (T2D), and assess the influence of
      covariates on observed SBP reductions. METHODS: A patient-level pooled analysis
      of six phase 3, randomized trials was conducted. RESULTS: The analysis included
      2792 randomized patients. In the intention-to-treat population (n=2783), mean [+/
      SE] SBP reductions from baseline with liraglutide 1.2 mg (2.7 [0.8] mmHg) and 1.8
      mg (2.9 [0.7] mmHg) once daily were significantly greater than with placebo (0.5
      [0.9] mmHg; P=0.0029 and P=0.0004, respectively) after 26 weeks, and were evident
      after 2 weeks. Liraglutide was also associated with significantly greater SBP
      reductions than glimepiride and, at a dose of 1.8 mg, insulin glargine and
      rosiglitazone. SBP reductions with liraglutide weakly correlated with weight loss
      (Pearson's correlation coefficient: 0.08-0.12; P<=0.0148). No dependence of these
      reductions on concomitant antihypertensive medications was detected (P=0.1304).
      Liraglutide 1.2 and 1.8 mg were associated with mean increases in pulse of 3
      beats per minute (bpm), versus a 1 bpm increase with placebo (P<0.0001 for each
      dose versus placebo). CONCLUSIONS: Liraglutide reduces SBP in patients with T2D,
      including those receiving concomitant antihypertensive medication.

PMID- 24561129
TI  - Food pellets as an effective delivery method for a DNA vaccine against infectious
      pancreatic necrosis virus in rainbow trout (Oncorhynchus mykiss, Walbaum).
AB  - A DNA vaccine based on the VP2 gene of infectious pancreatic necrosis virus
      (IPNV) was incorporated into feed to evaluate the effectiveness of this oral
      delivery method in rainbow trout. Lyophilized alginate-plasmid complexes were
      added to feed dissolved in water and the mixture was then lyophilized again. We
      compared rainbow trout that were fed for 3 consecutive days with vaccine pellets
      with fish that received the empty plasmid or a commercial pellet. VP2 gene
      expression could be detected in tissues of different organs in the rainbow trout
      that received the pcDNA-VP2 coated feed (kidney, spleen, gut and gill) throughout
      the 15 day time-course of the experiments. This pcDNA-VP2 vaccine clearly induced
      an innate and specific immune-response, significantly up-regulating IFN-1, IFN
      gamma, Mx-1, IL8, IL12, IgM and IgT expression. Strong protection, with relative
      survival rates of 78%-85.9% were recorded in the vaccinated trout, which produced
      detectable levels of anti-IPNV neutralizing antibodies during 90 days at least.
      Indeed, IPNV replication was significantly down-regulated in the vaccinated fish
      45 days pi. 

PMID- 24561128
TI  - Function of two novel single-CRD containing C-type lectins in innate immunity
      from Eriocheir sinensis.
AB  - C-type lectin is one of the pattern-recognition proteins of the non-self-innate
      immune system in invertebrates. In this study, two novel C-type lectin cDNAs
      (EsCTL1 and EsCTL2) of Eriocheir sinensis were cloned and characterized. EsCTL1
      has 169 amino acids, whereas EsCTL2 has 164 amino acids. These two lectins
      contain one carbohydrate-recognition domain. Phylogenetic analysis showed that
      EsCTL1 and EsCTL2 were not clustered with other reported lectins from crabs.
      EsCTL1 and EsCTL2 were expressed only in the hepatopancreas, as detected by real
      time PCR. When healthy crabs were challenged with lipopolysaccharide (LPS),
      peptidoglycan (PGN), Staphylococcus aureus, or Aeromonas hydrophila, the
      expression levels of EsCTL1 and EsCTL2 were significantly regulated. The
      recombinant EsCTL1 and EsCTL2 can agglutinate both Gram-positive (S. aureus) and
      Gram-negative bacteria (Vibrio parahaemolyticus and A. hydrophila) in a Ca2+ 
      dependent manner. The recombinant EsCTL1 and EsCTL2 can directly bind to LPS and
      PGN and to all tested microorganisms (S. aureus, Bacillus thuringiensis, Bacillus
      subtilis, Escherichia coli, Vibrio natriegens, V. parahaemolyticus, and A.
      hydrophila). Furthermore, rEsCTL1 and rEsCTL2 may facilitate the clearance of V.
      parahaemolyticus in vivo. These results suggest that EsCTL1 and EsCTL2 may have
      important roles in the anti-bacterial immunity of Chinese mitten crab.

PMID- 24561130
TI  - Th17-like immune response in fish mucosal tissues after administration of live
      attenuated Vibrio anguillarum via different vaccination routes.
AB  - This study aimed to investigate the protective mucosal immunity elicited by live
      attenuated Vibrio anguillarum in fish. Zebrafish were immunized by bath or
      injection way, and undertook bath challenge at 28 days post vaccination. The
      results implied that bath vaccination was the better delivery route for inducing
      the protective immunity against bath challenge in zebrafish. The expressions of
      genes related to Th1, Th2 and Th17 cells were measured in the mucosal tissues of
      vaccinated and challenged zebrafish. Gene expression profiles showed that Th17
      like responses were induced in mucosal immune system by vaccination via bath and
      injection routes while Th1 and Th2-like responses were not remarkable. Compared
      to injection vaccination, bath vaccination elicited the intense Th17-like immune
      responses in the gut tissue of zebrafish. Additionally, in gills and skin, Th17
      like mucosal immunity elicited by injection vaccination occurred later than that
      by bath vaccination. Our results proved the immunological importance of gut in
      bath vaccination and the presence of two-compartmental model for immune response
      in zebrafish. In conclusion, bath vaccination more efficiently elicited
      protective Th17-like immunity than injection vaccination in mucosal tissues of
      vaccinated zebrafish. In turbot, effective immune protection against wild-type V.
      anguillarum was obtained by bath-vaccinated and the Th17-like responses were
      found in mucosal and systemic tissues. 

PMID- 24561131
TI  - Unifying family A GPCR theories of activation.
AB  - Several new pairs of active and inactive GPCR structures have recently been
      solved enabling detailed structural insight into the activation process, not only
      of rhodopsin but now also of the beta2 adrenergic, M2 muscarinic and adenosine
      A2A receptors. Combined with structural analyses they have enabled us to examine
      the different recent theories proposed for GPCR activation and show that they are
      all indeed parts of the same process, and are intrinsically related through their
      effect on the central hydrophobic core of GPCRs. This new unifying general
      process of activation is consistent with the identification of known
      constitutively active mutants and an in-depth conservational analysis of
      significant residues implicated in the process. 

PMID- 24561133
TI  - Aspiration thrombectomy: an easily forgiven "latecomer".

PMID- 24561132
TI  - Risk genes for schizophrenia: translational opportunities for drug discovery.
AB  - Despite intensive research over many years, the treatment of schizophrenia
      remains a major health issue. Current and emerging treatments for schizophrenia
      are based upon the classical dopamine and glutamate hypotheses of disease.
      Existing first and second generation antipsychotic drugs based upon the dopamine
      hypothesis are limited by their inability to treat all symptom domains and their
      undesirable side effect profiles. Third generation drugs based upon the glutamate
      hypothesis of disease are currently under evaluation but are more likely to be
      used as add on treatments. Hence there is a large unmet clinical need. A major
      challenge in neuropsychiatric disease research is the relatively limited
      knowledge of disease mechanisms. However, as our understanding of the genetic
      causes of the disease evolves, novel strategies for the development of improved
      therapeutic agents will become apparent. In this review we consider the current
      status of knowledge of the genetic basis of schizophrenia, including methods for
      identifying genetic variants associated with the disorder and how they impact on
      gene function. Although the genetic architecture of schizophrenia is complex,
      some targets amenable to pharmacological intervention can be discerned. We
      conclude that many challenges lie ahead but the stratification of patients
      according to biobehavioural constructs that cross existing disease
      classifications but with common genetic and neurobiological bases, offer
      opportunities for new approaches to effective drug discovery. 

PMID- 24561136
TI  - Reply: cardiovascular prevention in diabetes mellitus: no magic remedies.

PMID- 24561135
TI  - Impact of fluoroscopically-visible fluttering flap on clinical diagnosis of acute
      aortic dissection.

PMID- 24561134
TI  - Exome sequencing implicates an increased burden of rare potassium channel
      variants in the risk of drug-induced long QT interval syndrome.
AB  - OBJECTIVES: The aim of this study was to test the hypothesis that rare variants
      are associated with drug-induced long QT interval syndrome (diLQTS) and torsades
      de pointes. BACKGROUND: diLQTS is associated with the potentially fatal
      arrhythmia torsades de pointes. The contribution of rare genetic variants to the
      underlying genetic framework predisposing to diLQTS has not been systematically
      examined. METHODS: We performed whole-exome sequencing on 65 diLQTS patients and
      148 drug-exposed control subjects of European descent. We used rare variant
      analyses (variable threshold and sequence kernel association test) and gene-set
      analyses to identify genes enriched with rare amino acid coding (AAC) variants
      associated with diLQTS. Significant associations were reanalyzed by comparing
      diLQTS patients with 515 ethnically matched control subjects from the National
      Heart, Lung, and Blood Grand Opportunity Exome Sequencing Project. RESULTS: Rare
      variants in 7 genes were enriched in the diLQTS patients according to the
      sequence kernel association test or variable threshold compared with drug-exposed
      controls (p < 0.001). Of these, we replicated the diLQTS associations for KCNE1
      and ACN9 using 515 Exome Sequencing Project control subjects (p < 0.05). A total
      of 37% of the diLQTS patients also had 1 or more rare AAC variants compared with
      21% of control subjects (p = 0.009), in a pre-defined set of 7 congenital long QT
      interval syndrome (cLQTS) genes encoding potassium channels or channel modulators
      (KCNE1, KCNE2, KCNH2, KCNJ2, KCNJ5, KCNQ1, AKAP9). CONCLUSIONS: By combining
      whole-exome sequencing with aggregated rare variant analyses, we implicate rare
      variants in KCNE1 and ACN9 as risk factors for diLQTS. Moreover, diLQTS patients
      were more burdened by rare AAC variants in cLQTS genes encoding potassium channel
      modulators, supporting the idea that multiple rare variants, notably across cLQTS
      genes, predispose to diLQTS.

PMID- 24561137
TI  - Prognostic value of myocardial scar in atrial fibrillation.

PMID- 24561138
TI  - Reply: prognostic value of myocardial scar in atrial fibrillation.

PMID- 24561139
TI  - Cardiovascular prevention in diabetes mellitus: no magic remedies.

PMID- 24561140
TI  - Drug-induced long QT syndrome and exome sequencing: Chinese shadows link past and
      future.

PMID- 24561141
TI  - Polypills: essential medicines for cardiovascular disease secondary prevention?
AB  - In 1977, the World Health Organization (WHO) developed its first Model List of
      Essential Medicines to guide countries in the creation of national formularies
      and policies for access, quality, and use of essential medicines as part of
      achieving the right to health. In 2012, the WHO announced its goal of reducing
      the number of premature deaths (<70 years) due to noncommunicable chronic
      diseases by 25% by the year 2025, including the indicator that 50% of eligible
      people receive drugs to prevent myocardial infarction and stroke. Despite the
      large body of evidence supporting the use of pharmacological treatment for the
      secondary prevention of cardiovascular diseases (CVD), substantial gaps in
      coverage of secondary interventions for prevention of CVD are widespread
      globally. Fixed dose combination, or polypill, therapy has been shown to improve
      adherence by 33% compared with usual care in CVD secondary prevention and has
      been recommended as a "best buy" by the WHO. In November 2012, along with 5 other
      scientists, we submitted an application to the Model List of Essential Medicines
      to include polypill therapy for secondary CVD prevention. In July 2013, the
      updated 18th Model List of Essential Medicines was released without inclusion of
      polypill therapy for secondary CVD prevention. In this article, we argue that
      polypill therapy meets the criteria for essential medicines and that inclusion in
      the Model List of Essential Medicines will facilitate its access and has the
      potential to avoid a few million premature deaths and related morbidity from CVD
      at low cost.

PMID- 24561142
TI  - Differential cyanosis and clubbing sparing a single limb.

PMID- 24561143
TI  - Marshaling the autonomic nervous system for treatment of atrial fibrillation.

PMID- 24561144
TI  - The curse of target lesion calcification: still active after all these years.

PMID- 24561145
TI  - Ischemic outcomes after coronary intervention of calcified vessels in acute
      coronary syndromes. Pooled analysis from the HORIZONS-AMI (Harmonizing Outcomes
      With Revascularization and Stents in Acute Myocardial Infarction) and ACUITY
      (Acute Catheterization and Urgent Intervention Triage Strategy) TRIALS.
AB  - OBJECTIVES: This study sought to determine the frequency and impact of coronary
      calcification among patients undergoing percutaneous coronary intervention (PCI)
      for acute coronary syndromes (ACS). BACKGROUND: Small studies in patients with
      stable coronary artery disease have suggested a worse prognosis after PCI of
      calcified compared with noncalcified lesions. Little is known about the impact of
      coronary calcification on outcomes after PCI for patients presenting with non-ST
      segment elevation and ST-segment elevation ACS. METHODS: Data from 6,855 patients
      presenting with ACS in whom PCI was performed were pooled from 2 large-scale
      randomized, controlled trials, ACUITY (Acute Catheterization and Urgent
      Intervention Triage Strategy) and HORIZONS-AMI (Harmonizing Outcomes With
      Revascularization and Stents in Acute Myocardial Infarction). One-year outcomes
      were analyzed according to the severity of PCI target lesion calcification
      (none/mild, moderate, or severe) as assessed by an independent angiographic core
      laboratory. RESULTS: Target lesion calcification was severe in 402 patients
      (5.9%), moderate in 1,788 (26.1%), and none/mild in 4,665 (68.1%).
      Moderate/severe target lesion calcification was more frequent in older patients,
      men, hypertensive patients, and those presenting with ST-segment elevation
      myocardial infarction (STEMI). The unadjusted 1-year rates of death, cardiac
      death, definite stent thrombosis, and ischemic target lesion revascularization
      (TLR) and target vessel revascularization were significantly increased in
      patients with moderate/severe target lesion calcification. By multivariable
      analysis, the presence of moderate/severe target lesion calcification was an
      independent predictor of 1-year definite stent thrombosis (hazard ratio [HR]:
      1.62; 95% confidence interval [CI]: 1.14 to 2.30; p = 0.007) and ischemic TLR
      (HR: 1.44; 95% CI: 1.17 to 1.78; p = 0.0007). CONCLUSIONS: Moderate/severe lesion
      calcification was relatively frequent in patients with non-ST-segment elevation
      ACS and STEMI and was strongly predictive of stent thrombosis and ischemic TLR at
      1 year. (Comparison of Angiomax Versus Heparin in Acute Coronary Syndromes [ACS];
      NCT00093158; Harmonizing Outcomes With Revascularization and Stents in Acute
      Myocardial Infarction; NCT00433966).

PMID- 24561147
TI  - Normalization of function in pediatric dilated cardiomyopathy: recovery or
      remission?

PMID- 24561146
TI  - Recovery of echocardiographic function in children with idiopathic dilated
      cardiomyopathy: results from the pediatric cardiomyopathy registry.
AB  - OBJECTIVES: This study sought to determine the incidence and predictors of
      recovery of normal echocardiographic function among children with idiopathic
      dilated cardiomyopathy (DCM). BACKGROUND: Most children with idiopathic DCM have
      poor outcomes; however, some improve. METHODS: We studied children <18 years of
      age from the Pediatric Cardiomyopathy Registry who had both depressed left
      ventricular (LV) function (fractional shortening or ejection fraction z-score <
      2) and LV dilation (end-diastolic dimension [LVEDD] z-score >2) at diagnosis and
      who had at least 1 follow-up echocardiogram 30 days to 2 years from the initial
      echocardiogram. We estimated the cumulative incidence and predictors of
      normalization. RESULTS: Among 868 children who met the inclusion criteria, 741
      (85%) had both echocardiograms. At 2 years, 22% had recovered normal LV function
      and size; 51% had died or undergone heart transplantation (median, 3.2 months),
      and 27% had persistently abnormal echocardiograms. Younger age (hazard ratio
      [HR]: 0.92; 95% confidence interval [CI]: 0.88 to 0.97) and lower LVEDD z-score
      (HR: 0.78; 95% CI: 0.70 to 0.87) independently predicted normalization. Nine
      children (9%) with normal LV function and size within 2 years of diagnosis later
      underwent heart transplantation or died. CONCLUSIONS: Despite marked LV dilation
      and depressed function initially, children with idiopathic DCM can recover normal
      LV size and function, particularly those younger and with less LV dilation at
      diagnosis. Investigations related to predictors of recovery, such as genetic
      associations, serum markers, and the impact of medical therapy or ventricular
      unloading with assist devices are important next steps. Longer follow-up after
      normalization is warranted as cardiac failure can recur. (Pediatric
      Cardiomyopathy Registry; NCT00005391).

PMID- 24561148
TI  - Ticagrelor effects on myocardial infarction and the impact of event adjudication
      in the PLATO (Platelet Inhibition and Patient Outcomes) trial.
AB  - OBJECTIVES: This study sought to report the treatment effect of ticagrelor on
      myocardial infarction (MI) and the strategy for and impact of event adjudication
      in the PLATO (Platelet Inhibition and Patient Outcomes) trial. BACKGROUND: In
      PLATO, ticagrelor reduced cardiovascular death, MI, or stroke in patients with
      acute coronary syndromes (ACS). METHODS: A clinical events committee (CEC)
      prospectively defined and adjudicated all suspected MI events, on the basis of
      events reported by investigators and by triggers on biomarkers. Treatment
      comparisons used CEC-adjudicated data, and per protocol, excluded silent MI.
      RESULTS: Overall, 1,299 (610 ticagrelor, 689 clopidogrel) MIs reported by the CEC
      occurred during the trial. Of these, 1,097 (504 ticagrelor, 593 clopidogrel)
      contributed to the primary composite endpoint. Site investigators reported 1,198
      (580 ticagrelor, 618 clopidogrel) MIs. Ticagrelor significantly reduced overall
      MI rates (12-month CEC-adjudicated Kaplan-Meier rates: 5.8% ticagrelor, 6.9%
      clopidogrel; hazard ratio [HR]: 0.84; 95% confidence interval [CI]: 0.75 to
      0.95). Nonprocedural MI (HR: 0.86; 95% CI: 0.74 to 1.01) and MI related to
      percutaneous coronary intervention or stent thrombosis tended to be lower with
      ticagrelor. MIs related to coronary artery bypass graft surgery were few, but
      numerical excess was observed in patients assigned ticagrelor. Analyses of
      overall MIs using investigator-reported data showed similar results but did not
      reach statistical significance (HR: 0.88; 95% CI: 0.78 to 1.00). CONCLUSIONS: In
      patients with ACS, ticagrelor significantly reduced the incidence of MI compared
      with clopidogrel, with consistent results across most MI subtypes. CEC procedures
      identified more MI endpoints compared with site investigators. (A Comparison of
      Ticagrelor [AZD6140] and Clopidogrel in Patients With Acute Coronary Syndrome
      [PLATO]; NCT00391872).

PMID- 24561149
TI  - Sex-related differences in outcomes after transcatheter or surgical aortic valve
      replacement in patients with severe aortic stenosis: Insights from the PARTNER
      Trial (Placement of Aortic Transcatheter Valve).
AB  - OBJECTIVES: This study sought to examine sex-specific differences in outcomes
      after surgical aortic valve replacement (SAVR) or transcatheter aortic valve
      replacement (TAVR) in high-risk patients with severe aortic stenosis. BACKGROUND:
      The PARTNER (Placement of Aortic Transcatheter Valve) trial demonstrated similar
      2-year survival with SAVR or TAVR for high-risk patients, but sex-specific
      outcomes are unknown. METHODS: In all, 699 patients (300 female) were randomly
      assigned 1:1 to either SAVR or TAVR with a balloon expandable pericardial tissue
      valve. Baseline characteristics and 2-year outcomes of TAVR versus SAVR were
      compared among males and females. RESULTS: Baseline characteristics differed
      between the sexes. Despite higher Society of Thoracic Surgeons mortality risk
      scores (11.9 vs. 11.6; p = 0.05), female patients had lower prevalence of
      coronary artery disease (64.4% vs. 83.7%), prior coronary artery bypass graft
      surgery (19.8% vs. 61.2%), peripheral vascular disease (36.4% vs. 46.9%),
      diabetes mellitus (35.6% vs. 45.6%), and elevated creatinine (11.7% vs. 23.9%).
      Among female patients, procedural mortality trended lower with TAVR versus SAVR
      (6.8% vs. 13.1%; p = 0.07) and was maintained throughout follow-up (hazard ratio
      [HR]: 0.67; 95% confidence interval [CI]: 0.44 to 1.00; p = 0.049), driven by the
      transfemoral arm (HR: 0.55; 95% CI: 0.32 to 0.93; p = 0.02). Among male patients,
      although procedural mortality was lower with TAVR (6% vs. 12.1%; p = 0.03), there
      was no overall survival benefit (HR: 1.15; 95% CI: 0.82 to 1.61; p = 0.42).
      CONCLUSIONS: In this retrospective subanalysis of high-risk, symptomatic aortic
      stenosis patients in the PARTNER trial, female subjects had lower late mortality
      with TAVR versus SAVR. This was especially true among patients suitable for
      transfemoral access and suggests that TAVR may be preferred over surgery for high
      risk female patients. A randomized, controlled trial conducted specifically in
      female patients is necessary to properly study differences in mortality between
      treatment modalities. (THE PARTNER TRIAL: Placement of AoRTic TraNscathetER Valve
      Trial; NCT00530894).

PMID- 24561150
TI  - Massive pericardial effusion and cardiac tamponade due to cholesterol
      pericarditis in a case of subclinical hypothyroidism: a rare event.

PMID- 24561152
TI  - Reply: aspiration thrombectomy: an easily forgiven "latecomer".

PMID- 24561151
TI  - Ethanol infusion in the vein of Marshall leads to parasympathetic denervation of
      the human left atrium: implications for atrial fibrillation.
AB  - OBJECTIVES: This study sought to determine whether ethanol infusion in the vein
      of Marshall (VOM) can ablate intrinsic cardiac nerves (ICN). BACKGROUND: ICN
      cluster around the left atrial epicardium and are implicated in the genesis of
      atrial fibrillation (AF). METHODS: Patients undergoing catheter AF ablation
      underwent adjunctive ethanol injection in the VOM. A multipolar catheter was
      introduced in the VOM and used for high-frequency stimulation (HFS), either as
      HFS with P-wave synchronized (SynchHFS), 30 pulses, 100 Hz (n = 8) or as HFS with
      3 to 10 s bursts (BurstHFS), 33 Hz (n = 72) at 25 mA for 1-ms duration.
      Atrioventricular (AV) nodal conduction slowing (asystole >2 s or R-R interval
      prolongation >50%) and AF inducibility were assessed before and after VOM ethanol
      infusion. Up to 4 1-ml infusions of 98% ethanol were delivered via an angioplasty
      balloon in the VOM. RESULTS: SynchHFS induced AF in 8 of 8 patients. In 4 of 8 AF
      initiated spontaneously without VOM capture. No parasympathetic responses were
      elicited by SynchHFS. BurstHFS was performed in 32 patients undergoing de novo AF
      ablation (Group 1) and 40 patients undergoing repeat ablation (Group 2).
      Parasympathetic responses were found in all 32 Group 1 patients and in 75% of
      Group 2 patients. After VOM ethanol infusion, parasympathetic responses were
      abolished in all patients (both groups). There were no acute complications
      related to VOM ethanol infusion. CONCLUSIONS: The VOM contains ICN that connect
      with the AV node and can trigger AF. Retrograde ethanol infusion in the VOM
      reliably eliminates local ICN responses. The VOM is a vascular route for ICN
      targeting therapies.

PMID- 24561153
TI  - Green tea (Camellia sinensis) extract inhibits both the metastasis and osteolytic
      components of mammary cancer 4T1 lesions in mice.
AB  - Green tea (Camellia sinensis, CS), a kind of Chinese tea commonly consumed as a
      healthy beverage, has been demonstrated to have various biological activities,
      including antioxidation, antiobesity and anticancer. Our study aims to
      investigate the antitumor, antimetastasis and antiosteolytic effects of CS
      aqueous extract both in vitro and in vivo using metastasis-specific mouse mammary
      carcinoma 4T1 cells. Our results showed that treatment of 4T1 cells with CS
      aqueous extract resulted in significant inhibition of 4T1 cell proliferation. CS
      extract induced 4T1 apoptosis in a dose-dependent manner as assessed by annexin-V
      and propidium iodide staining and caspase-3 activity. Western blot analysis
      showed that CS increased the expression of Bax-to-Bcl-2 ratio and activated
      caspase-8 and caspase-3 to induce apoptosis. CS also inhibited 4T1 cell migration
      and invasion at 0.06-0.125 mg/ml. In addition, CS extract (0.6 g/kg, orally fed
      daily for 4 weeks) was effective in decreasing the tumor weight by 34.8% in
      female BALB/c mice against water treatment control (100%). Apart from the
      antitumor effect, CS extract significantly decreased lung and liver metastasis in
      BALB/c mice bearing 4T1 tumors by 54.5% and 72.6%, respectively. Furthermore,
      micro-computed tomography and in vitro osteoclast staining analysis suggested
      that CS extract was effective in bone protection against breast cancer-induced
      bone destruction. In conclusion, the present study demonstrated that the CS
      aqueous extract, which closely mimics green tea beverage, has potent antitumor
      and antimetastasis effects in breast cancer and could protect the bone from
      breast cancer-induced bone destruction. 

PMID- 24561155
TI  - Activation of the prefrontal cortex and posterior parietal cortex increases the
      recognition of semantic violations in action representation.
AB  - BACKGROUND: The correct outcome of transitive actions depends on an object's use,
      considering both the instrumental and functional features. Indeed, the
      representation of transitive action includes the correct/incorrect instrumental
      use and the congruous/incongruous functional use of the object. OBJECTIVES: The
      contribution of frontal (experiment 1) and posterior parietal (experiment 2)
      areas to process semantic violations in instrumental vs. functional action
      representation was explored. METHODS: These cortical areas were appositely
      modulated by anodal tDCS (transcranial direct current stimulation) or sham tDCS
      when 43 healthy subjects processed semantic violations (congruous/incongruous
      pairs) and they had to perform an error detection task (measuring ERs - error
      rates; and RTs - response times). RESULTS: Decreased RTs were observed for
      incongruous pairs in the case of prefrontal stimulation compared to the sham
      condition. This effect was related to both the instrumental and functional
      conditions, suggesting that the activation of the prefrontal area may increase
      the ability to analyze the semantic incongruence independently from the anomaly
      type, which would limit the cognitive costs. In contrast, posterior parietal
      stimulation reduced RTs only in response to functional action in the case of
      semantic incongruence. CONCLUSIONS: Thus, different cortical contributions by
      anterior vs. posterior areas occurred in response to semantic incongruences
      respectively for generic expectancy violations (more frontally distributed) and
      specific functional violations (more parietally distributed).

PMID- 24561154
TI  - Dietary cocoa reduces metabolic endotoxemia and adipose tissue inflammation in
      high-fat fed mice.
AB  - In diet-induced obesity, adipose tissue (AT) is in a chronic state of
      inflammation predisposing the development of metabolic syndrome. Cocoa (Theobroma
      cacao) is a polyphenol-rich food with putative anti-inflammatory activities.
      Here, we examined the impact and underlying mechanisms of action of cocoa on AT
      inflammation in high fat-fed mice. In the present study, male C57BL/6 J mice were
      fed a high fat diet (HF), a HF diet with 8% (w/w) unsweetened cocoa powder (HFC),
      or a low-fat diet (LF) for 18 weeks. Cocoa supplementation decreased AT mRNA
      levels of tumor necrosis factor-alpha, interleukin-6, inducible nitric oxide
      synthase, and EGF-like module-containing mucin-like hormone receptor-like 1 by 40
      60% compared to HF group, and this was accompanied by decreased nuclear protein
      levels of nuclear factor-kappaB. Cocoa treatment reduced the levels of
      arachidonic acid in the AT by 33% compared to HF controls. Moreover, cocoa
      treatment also reduced protein levels of the eicosanoid-generating enzymes,
      adipose-specific phospholipase A2 and cyclooxygenase-2 by 53% and 55%,
      respectively, compared to HF-fed mice. Finally, cocoa treatment ameliorated
      metabolic endotoxemia (40% reduction in plasma endotoxin) and improved gut
      barrier function (as measured by increased plasma levels of glucagon-like peptide
      2). In conclusion, the present study has shown for the first time that long-term
      cocoa supplementation can reduce AT inflammation in part by modulating eicosanoid
      metabolism and metabolic endotoxemia.

PMID- 24561156
TI  - Post-transcriptional regulation of the creatine transporter gene: functional
      relevance of alternative splicing.
AB  - BACKGROUND: Aberrations in about 10-15% of X-chromosome genes account for
      intellectual disability (ID); with a prevalence of 1-3% (Gecz et al., 2009 [1]).
      The SLC6A8 gene, mapped to Xq28, encodes the creatine transporter (CTR1).
      Mutations in SLC6A8, and the ensuing decrease in brain creatine, lead to co
      occurrence of speech/language delay, autism-like behaviors and epilepsy with ID.
      A splice variant of SLC6A8-SLC6A8C, containing intron 4 and exons 5-13, was
      identified. Herein, we report the identification of a novel variant - SLC6A8D,
      and functional relevance of these isoforms. METHODS: Via (quantitative) RT-PCR,
      uptake assays, and confocal microscopy, we investigated their expression and
      function vis-a-vis creatine transport. RESULTS: SLC6A8D is homologous to SLC6A8C
      except for a deletion of exon 9 (without occurrence of a frame shift). Both
      contain an open reading frame encoding a truncated protein but otherwise
      identical to CTR1. Like SLC6A8, both variants are predominantly expressed in
      tissues with high energy requirement. Our experiments reveal that these truncated
      isoforms do not transport creatine. However, in SLC6A8 (CTR1)-overexpressing
      cells, a subsequent infection (transduction) with viral constructs encoding
      either the SLC6A8C (CTR4) or SLC6A8D (CTR5) isoform resulted in a significant
      increase in creatine accumulation compared to CTR1 cells re-infected with viral
      constructs containing the empty vector. Moreover, transient transfection of CTR4
      or CTR5 into HEK293 cells resulted in significantly higher creatine uptake.
      CONCLUSIONS: CTR4 and CTR5 are possible regulators of the creatine transporter
      since their overexpression results in upregulated CTR1 protein and creatine
      uptake. GENERAL SIGNIFICANCE: Provides added insight into the mechanism(s) of
      creatine transport regulation.

PMID- 24561158
TI  - Incessant long RP tachycardia: what is the mechanism?

PMID- 24561157
TI  - Number and Brightness analysis of alpha-synuclein oligomerization and the
      associated mitochondrial morphology alterations in live cells.
AB  - BACKGROUND: Alpha-synuclein oligomerization is associated to Parkinson's disease
      etiopathogenesis. The study of alpha-synuclein oligomerization properties in live
      cell and the definition of their effects on cellular viability are among fields
      expected to provide the knowledge required to unravel the mechanism(s) of
      toxicity that lead to the disease. METHODS: We used Number and Brightness method,
      which is a method based on fluorescence fluctuation analysis, to monitor alpha
      synuclein tagged with EGFP aggregation in living SH-SY5Y cells. The presence of
      alpha-synuclein oligomers detected with this method was associated with
      intracellular structure conditions, evaluated by fluorescence confocal imaging.
      RESULTS: Cells overexpressing alpha-synuclein-EGFP present a heterogeneous
      ensemble of oligomers constituted by less than 10 monomers, when the protein
      approaches a threshold concentration value of about 90nM in the cell cytoplasm.
      We show that the oligomeric species are partially sequestered by lysosomes and
      that the mitochondria morphology is altered in cells presenting oligomers,
      suggesting that these mitochondria may be dysfunctional. CONCLUSIONS: We showed
      that alpha-synuclein overexpression in SH-SY5Y causes the formation of alpha
      synuclein oligomeric species, whose presence is associated with mitochondrial
      fragmentation and autophagic-lysosomal pathway activation in live cells. GENERAL
      SIGNIFICANCE: The unique capability provided by the Number and Brightness
      analysis to study alpha-synuclein oligomer distribution and properties, and the
      study of their association to intracellular components in single live cells is
      important to forward our understanding of the molecular mechanisms of Parkinson's
      disease and it may be of general significance when applied to the study of other
      aggregating proteins in cellular models.

PMID- 24561159
TI  - Sinus rhythm detection of conducting channels and ventricular tachycardia isthmus
      in arrhythmogenic right ventricular cardiomyopathy.
AB  - BACKGROUND: The identification of conducting channels (CCs) based on its relative
      high voltage or the presence of electrograms with delayed components has been
      proposed for substrate-guided scar-related ventricular tachycardia (VT) ablation.
      The relationship of these channels with the VT isthmuses remains unclear.
      OBJECTIVE: To assess the link between CCs identified during sinus rhythm (SR) and
      VT isthmuses in patients with arrhythmogenic right ventricular cardiomyopathy
      (ARVC). METHODS: Twenty-two consecutive patients with ARVC undergoing substrate
      guided VT ablation (scar dechanneling technique) were analyzed. High-density
      endocardial and epicardial electroanatomic maps were obtained during SR. Standard
      bipolar cutoff values (0.5-1.5 and <0.5 mV) were used to define border zone and
      dense scar. The CCs were identified by voltage threshold adjustment (voltage
      channels) or by tagging the electrograms with delayed components that are
      sequentially activated (late potential channels). RESULTS: A total of 87 CCs were
      identified; 65 (74.7%) of them on the epicardial surface. Twenty-four (27.6%) CCs
      were voltage channels, and compared with late potential CCs, these had a higher
      bipolar voltage (0.96 [0.48-1.29] mV vs 0.39 [0.26-0.50] mV; P < .001] and
      required more radiofrequency applications (5 [4-7] vs 3 [2-5]; P = .048].
      Eighteen (90%) of 20 identified VT isthmuses were located on the epicardium. Only
      8 (40%) VT isthmuses were related to a voltage CC. The remaining 12 (60%) VT
      isthmuses were linked to a late potential CC. CONCLUSION: Late potential CCs more
      frequently act as the VT substrate in ARVC and therefore should also be
      considered to guide SR substrate-guided ablation.

PMID- 24561160
TI  - Discriminating atrial flutter from atrial fibrillation using a multilevel model
      of atrioventricular conduction.
AB  - BACKGROUND: The discrimination between atrial flutter (AFlu) and atrial
      fibrillation (AFib) can be made difficult by an irregular ventricular response
      owing to complex conduction phenomena within the atrioventricular (AV) node,
      known as multilevel AV block. We tested the hypothesis that a mathematical
      algorithm might be suitable to discriminate both arrhythmias. OBJECTIVES: To
      discriminate AFlu with irregular ventricular response from AFib based on the
      sequence of R-R intervals. METHODS: Intracardiac recordings of 100 patients (50
      patients with AFib and 50 patients with AFlu) were analyzed. On the basis of a
      numerical simulation of variable flutter frequencies followed by 2 levels of AV
      block in series, a given sequence of R-R intervals was analyzed. RESULTS:
      Although the ventricular response displays absolute irregularity in AFib, the
      sequences of R-R intervals follow certain rules in AFlu. We find that using a
      mathematical simulation of multilevel AV block, based on the R-R sequence of 16
      ventricular beats, a stability of atrial activation could be predicted with a
      sensitivity of 84% and a specificity of 74%. When limiting the ventricular rate
      to 125 beats/min, discrimination could be performed with a sensitivity of even
      89% and a specificity of 80%. In cases of AFlu, the atrial cycle length could be
      predicted with high accuracy. CONCLUSION: On the basis of the
      electrophysiological mechanism of multilevel AV block, we developed a computer
      algorithm to discriminate between AFlu and Afib. This algorithm is able to
      predict the stability and cycle length of atrial activation for short R-R
      sequences with high accuracy.

PMID- 24561161
TI  - Cardiac resynchronization therapy restored ventricular septal myocardial
      perfusion and enhanced ventricular remodeling in patients with nonischemic
      cardiomyopathy presenting with left bundle branch block.
AB  - BACKGROUND: Left bundle branch block (LBBB) causes intraventricular conductional
      delay, which results in left ventricle (LV) mechanical dyssynchrony. In the
      absence of coronary artery disease, patients with LBBB often have diminished
      accumulation of technetium-99m compounds at the myocardial septal area in
      electrocardiogram-gated single-photon emission computed tomography. OBJECTIVE: To
      investigate whether cardiac resynchronization therapy (CRT) could improve septal
      myocardial perfusion, leading to favorable reverse remodeling. METHODS: The study
      included all 26 patients with nonischemic cardiomyopathy eligible for CRT, who
      presented with LBBB, New York Heart Association class II-IV heart failure, and LV
      ejection fraction <=35%. Single-photon emission computed tomography was performed
      at baseline and 6 months after CRT. Perfusion counts were measured at the
      ventricular septum and LV lateral free wall. Left ventricular end-systolic volume
      (LVESV) was measured by echocardiography to evaluate LV reverse remodeling by
      CRT. RESULTS: At baseline, a perfusion defect at the LV septal myocardial area
      was confirmed in 19 of 26 (73%) patients. In these patients, septal perfusion
      significantly increased 6 months after CRT (56.1% +/- 22.8% vs 82.9% +/- 21.2%; P
      < .001). LVESV reduction and improved septal perfusion index were positively
      correlated (r = .561; P = .012), whereas no correlation was found between LVESV
      reduction and the difference of QRS duration before and 6 months after CRT (r =
      .218; P = .371). The improvement in LV septal perfusion was associated with LV
      reverse remodeling. CONCLUSIONS: CRT could restore LV septal myocardial perfusion
      and ameliorate ventricular reverse remodeling in most patients with nonischemic
      cardiomyopathy and LBBB.

PMID- 24561162
TI  - Scar progression in patients with nonischemic cardiomyopathy and ventricular
      arrhythmias.
AB  - BACKGROUND: Disease progression in patients with nonischemic cardiomyopathy
      (NICM) is poorly understood. OBJECTIVE: To assess left ventricular (LV) scar
      progression and dilatation by using endocardial electroanatomic mapping. METHODS:
      We studied 13 patients with NICM and recurrent ventricular tachycardia. Two
      detailed sinus rhythm endocardial voltage maps (265 +/- 122 points/map) were
      obtained after a mean of 32 months (range 9-77 months). The scar area, defined by
      low bipolar (BI; <1.5 mV) and unipolar (UNI; <8.3 mV) endocardial voltage, and
      the LV volume were measured and compared. A scar difference of >6% of the LV
      surface and an increase in LV volume of >=20 mL were considered beyond
      measurement error. RESULTS: Six (46%) patients had an increase in scar area
      beyond boundaries of prior ablation. Five patients had an increase in UNI and 1
      patient had an increase in both BI and UNI areas. The increase in BI area
      represented 16% and the increase in UNI area represented 6.5%-46.2% of the LV
      surface. A significant decrease in LV ejection fraction was found only in
      patients with scar progression (from 39% +/- 8% to 32% +/- 8%; P = .003). LV
      dilation (LV volume increase ranging between 9% and 23%) was noted in 3 patients,
      all of whom had scar progression. CONCLUSIONS: Progressive scarring with an
      increase in the area of UNI and less commonly BI electrogram abnormality is seen
      in 46% of the patients with NICM and ventricular tachycardia and is associated
      with LV dilatation and decrease in LV ejection fraction. The prominent UNI
      abnormality suggests predominantly midmyocardial or epicardial scarring.

PMID- 24561163
TI  - A pacemaker transthoracic impedance sensor with an advanced algorithm to identify
      severe sleep apnea: the DREAM European study.
AB  - BACKGROUND: Sleep apnea (SA) is associated with cardiovascular diseases and is
      highly prevalent in patients with pacemakers (PMs). OBJECTIVE: To validate a
      transthoracic impedance sensor with an advanced algorithm (sleep apnea
      monitoring) for identifying severe SA. METHODS: Patients with indications for PM
      (VVI/DDD) were enrolled regardless of symptoms suggesting SA. Severe SA diagnosis
      was acknowledged when the full polysomnography gave an apnea-hypopnea index (PSG
      AHI) of >=30 events/h. The PSG-AHI was compared with the respiratory disturbance
      index evaluated by the SAM algorithm (SAM-RDI) compiled from the device during
      the same diagnosis night, and the performance of the device and the SAM algorithm
      was calculated to identify patients with severe SA. The agreement between methods
      was assessed by using Bland and Altman statistics. RESULTS: Forty patients (mean
      age 73.8 +/- 19.1 years; 67.5% men; body mass index 27.7 +/- 4.4 kg/m(2)) were
      included. Severe SA was diagnosed by PSG in 56% of the patients. We did not
      retrieve SAM-RDI data in 14% of the patients. An optimal cutoff value for the SAM
      RDI at 20 events/h was obtained by a receiver operator characteristic curve
      analysis, which yielded a sensitivity of 88.9% (95% confidence interval [CI]
      65.3%-98.6%), a positive predictive value of 88.9% (95% CI 65.3%-98.6%), and a
      specificity of 84.6% (95% CI 54.6%-98.1%) (n = 31). The Bland-Altman limits of
      agreement for PSG-AHI (in events per hour) were [-14.1 to 32.4]. CONCLUSION: The
      results suggest that an advanced algorithm using PM transthoracic impedance could
      be used to identify SA in patients with PMs outside the clinic or at home.

PMID- 24561164
TI  - Long-term progression from paroxysmal to permanent atrial fibrillation following
      transcatheter ablation in a large single-center experience.
AB  - BACKGROUND: The natural history of atrial fibrillation (AF) is characterized by
      gradual increase in duration and frequency of relapses until a definitive shift
      to permanent AF. Heart disease and comorbidities modulate AF progression.
      However, to date the influence of catheter ablation on AF evolution has rarely
      been investigated. OBJECTIVE: The purpose of this study was to identify long-term
      predictors of AF progression in a large cohort of patients undergoing AF
      transcatheter ablation (AFTCA). METHODS: A total of 889 patients (mean age 57 +/-
      11 years; 53.3% paroxysmal AF, 40.5% persistent AF, 6.2% long-standing AF)
      underwent AFTCA. All patients underwent pulmonary vein isolation, with linear
      lesions and complex fractionated atrial electrogram ablation reserved for
      patients with persistent/long-standing AF and/or confirmed structural heart
      disease. RESULTS: After median follow-up of 64 months (range 41-84 years), AF
      progression despite AFTCA occurred in 57 cases (6.4%). However, AF progression
      was much more pronounced in patients with persistent (10%) or long-standing
      persistent AF (14.6%) than in those with paroxysmal AF (2.7%, P <.001).
      Furthermore, AF progression was more frequently reported in patients who
      presented with underlying comorbidities/cardiomyopathies (9.1%) than in those who
      presented with lone AF (29.9%, P <.001). At multivariate analysis,
      comorbidities/cardiomyopathies and baseline persistent/long-standing AF proved to
      be independent predictors of progression (odds ratio 11.3, 95% confidence
      interval 2.6-48.0, P <.001, and odds ratio 1.6, 95% confidence interval 1.2-2.1,
      P <.001, respectively). CONCLUSION: The presence of
      comorbidities/cardiomyopathies and persistent/long-standing AF seem to predict AF
      progression in patients undergoing AFTCA. Performing AFTCA in the paroxysmal
      phase of the arrhythmia may reduce progression of AF to its permanent form.

PMID- 24561165
TI  - Generation of knockout mice using engineered nucleases.
AB  - The use of engineered nucleases in one-cell stage mouse embryos is emerging as an
      efficient alternative to conventional gene targeting in mouse embryonic stem (ES)
      cells. These nucleases are designed or reprogrammed to specifically induce double
      strand breaks (DSBs) at a desired genomic locus, and efficiently introduce
      mutations by both error-prone and error-free DNA repair mechanisms. Since these
      mutations frequently result in the loss or alteration of gene function by
      inserting, deleting, or substituting nucleotide sequences, engineered nucleases
      are enabling us to efficiently generate gene knockout and knockin mice. Three
      kinds of engineered endonucleases have been developed and successfully applied to
      the generation of mutant mice: zinc-finger nuclease (ZFNs), transcription
      activator-like effector nucleases (TALENs) and RNA-guided endonucleases (RGENs).
      Based on recent advances, here we provide experimentally validated, detailed
      guidelines for generating non-homologous end-joining (NHEJ)-mediated mutant mice
      by microinjecting TALENs and RGENs into the cytoplasm or the pronucleus of one
      cell stage mouse embryos. 

PMID- 24561166
TI  - Live-cell fluorescent microscopy platforms for real-time monitoring of polyplex
      cell interaction: basic guidelines.
AB  - A myriad of cationic polymeric delivery vehicles are currently being developed
      with the aim of transporting various forms of nucleic acids to mammalian cells.
      The complexes between polycations and nucleic acids are referred to as
      polyplexes. The screening for successful polyplex candidates requires
      interdisciplinary research platforms and techniques for a more profound
      understanding of biophysical properties of delivery vehicles and their biological
      performance, including stability, transfection efficacy and possible
      cytotoxicity. Fluorescent microscopy has proven to be a useful tool for real-time
      monitoring of performance and intracellular trafficking of polyplexes as well as
      for assessing cell functionality. This review highlights the application of some
      of the most promising fluorescent microscopy platforms in relation to polyplex
      mediated transfection processes. 

PMID- 24561167
TI  - Gene Ontology based housekeeping gene selection for RNA-seq normalization.
AB  - RNA-seq analysis provides a powerful tool for revealing relationships between
      gene expression level and biological function of proteins. In order to identify
      differentially expressed genes among various RNA-seq datasets obtained from
      different experimental designs, an appropriate normalization method for
      calibrating multiple experimental datasets is the first challenging problem. We
      propose a novel method to facilitate biologists in selecting a set of suitable
      housekeeping genes for inter-sample normalization. The approach is achieved by
      adopting user defined experimentally related keywords, GO annotations, GO term
      distance matrices, orthologous housekeeping gene candidates, and stability
      ranking of housekeeping genes. By identifying the most distanced GO terms from
      query keywords and selecting housekeeping gene candidates with low coefficients
      of variation among different spatio-temporal datasets, the proposed method can
      automatically enumerate a set of functionally irrelevant housekeeping genes for
      pratical normalization. Novel and benchmark testing RNA-seq datasets were applied
      to demostrate that different selections of housekeeping gene lead to strong
      impact on differential gene expression analysis, and compared results have shown
      that our proposed method outperformed other traditional approaches in terms of
      both sensitivity and specificity. The proposed mechanism of selecting appropriate
      houskeeping genes for inter-dataset normalization is robust and accurate for
      differential expression analyses. 

PMID- 24561169
TI  - Choroidal analysis in healthy eyes using swept-source optical coherence
      tomography compared to spectral domain optical coherence tomography.
AB  - PURPOSE: To compare analyses of choroidal thickness and volume in healthy eyes
      measured concurrently with prototype long-wavelength swept-source optical
      coherence tomography (OCT) and commercially available spectral-domain optical
      coherence tomography (OCT) with and without enhanced depth imaging (EDI). DESIGN:
      Prospective cross sectional study. METHODS: The study included 19 healthy
      subjects (19 eyes), who were prospectively recruited to undergo 2 consecutive
      imaging sessions on the same randomly selected eye using spectral domain OCT and
      a prototype long-wavelength swept-source OCT. On spectral domain OCT, 2 line
      scans, 1 with and 1 without EDI, and 1 volumetric scan were obtained. On swept
      source OCT, 1 line scan and 1 volumetric scan were obtained. Scan patterns on
      swept-source OCT were created to simulate those available on Cirrus HD-OCT to
      keep the time of image acquisition constant. Swept-source OCT volumetric scans
      were motion corrected using a novel registration algorithm. Choroidal thickness
      and volume were analyzed. RESULTS: The choroidoscleral interface was clearly
      visualized in 19/19 (100%) of eyes imaged by swept-source OCT, compared to 14/19
      (73.6%) and 13/19 (68.4%) eyes imaged by spectral domain OCT, with and without
      EDI, respectively. There was no significant difference in choroidal thickness
      measurements on the line scans obtained on either system (P = 0.10). Choroidal
      volume could not be assessed on volumetric scans from spectral domain OCT. Mean
      choroidal volume from swept-source OCT volumetric scans was 11.77 +/- 3.13 mm(3)
      (6.43 mm(3)-17.15 mm(3)). CONCLUSION: This is the first study that compares
      simultaneously a prototype long-wavelength swept-source OCT to a commercially
      available spectral domain OCT for a detailed analysis of choroid in healthy eyes.
      Swept-source OCT shows potential for better choroidal analysis. Studies using
      swept-source OCT in diseased eyes will further define this new technology's
      utility in chorioretinal diseases.

PMID- 24561170
TI  - Comparison of long-term surgical outcomes of 2-muscle surgery in children with
      large-angle exotropia: bilateral vs unilateral.
AB  - PURPOSE: To evaluate the long-term results of 2-muscle surgery in children with
      primary large-angle exotropia, comparing 10 mm bilateral lateral rectus recession
      (BLR) with unilateral lateral rectus recession-medial rectus resection
      (recess/resect). DESIGN: Retrospective case series. METHODS: Eighty-six children
      with exotropia of >=40 prism diopters (PD), who underwent the 10 mm BLR (BLR
      group) or the unilateral recess/resect procedure (RR group) based on the largest
      angle measured at distance or near were included. Patients were followed-up for
      more than 2 years. Final successful alignment rates, stereopsis, and factors
      related to recurrence and overcorrection were evaluated. RESULTS: At the final
      examination, 29 (60.4%) of 48 patients in the BLR group achieved successful
      alignment; 16 (33.3%) had recurrence, and 3 (6.3%) had overcorrection. In the RR
      group, 26 of 38 patients (68.4%) were successfully aligned, 10 (26.3%) had
      recurrence, and 2 (5.3%) had overcorrection. Successful alignment and recurrence
      rates were not significantly different in the groups (P = .371 and .640,
      respectively). The overcorrection rate was significantly higher in the RR group
      (P = .014) until 2 years after surgery, but this difference was not significant
      afterward (P = 1.000). In patients with an exodeviation of >=45 PD, the
      recess/resect procedure showed higher successful alignment rates at the final
      examination (P = .006). CONCLUSIONS: The long-term successful alignment rate of 2
      muscle surgery in children with primary large-angle exotropia was 64%, and the
      overall surgical outcomes were comparable between the BLR and RR groups. However,
      in patients with exotropia of >=45 PD, the unilateral recess/resect procedure
      resulted in more favorable long-term outcomes.

PMID- 24561168
TI  - Incorporating inter-relationships between different levels of genomic data into
      cancer clinical outcome prediction.
AB  - In order to improve our understanding of cancer and develop multi-layered
      theoretical models for the underlying mechanism, it is essential to have enhanced
      understanding of the interactions between multiple levels of genomic data that
      contribute to tumor formation and progression. Although there exist recent
      approaches such as a graph-based framework that integrates multi-omics data
      including copy number alteration, methylation, gene expression, and miRNA data
      for cancer clinical outcome prediction, most of previous methods treat each
      genomic data as independent and the possible interplay between them is not
      explicitly incorporated to the model. However, cancer is dysregulated by multiple
      levels in the biological system through genomic, epigenomic, transcriptomic, and
      proteomic level. Thus, genomic features are likely to interact with other genomic
      features in the different genomic levels. In order to deepen our knowledge, it
      would be desirable to incorporate such inter-relationship information when
      integrating multi-omics data for cancer clinical outcome prediction. In this
      study, we propose a new graph-based framework that integrates not only multi
      omics data but inter-relationship between them for better elucidating cancer
      clinical outcomes. In order to highlight the validity of the proposed framework,
      serous cystadenocarcinoma data from TCGA was adopted as a pilot task. The
      proposed model incorporating inter-relationship between different genomic
      features showed significantly improved performance compared to the model that
      does not consider inter-relationship when integrating multi-omics data. For the
      pair between miRNA and gene expression data, the model integrating miRNA, for
      example, gene expression, and inter-relationship between them with an AUC of
      0.8476 (REI) outperformed the model combining miRNA and gene expression data with
      an AUC of 0.8404. Similar results were also obtained for other pairs between
      different levels of genomic data. Integration of different levels of data and
      inter-relationship between them can aid in extracting new biological knowledge by
      drawing an integrative conclusion from many pieces of information collected from
      diverse types of genomic data, eventually leading to more effective screening
      strategies and alternative therapies that may improve outcomes. 

PMID- 24561171
TI  - Successful treatment of diplopia with prism improves health-related quality of
      life.
AB  - PURPOSE: To report change in strabismus-specific health-related quality of life
      (HRQOL) following treatment with prism. DESIGN: Retrospective cross-sectional
      study. METHODS: Thirty-four patients with diplopia (median age 63, range 14-84
      years) completed the Adult Strabismus-20 questionnaire (100-0, best to worst
      HRQOL) and a diplopia questionnaire in a clinical practice before prism and in
      prism correction. Before prism, diplopia was "sometimes" or worse for reading
      and/or straight-ahead distance. Prism treatment success was defined as diplopia
      rated "never" or "rarely" on the diplopia questionnaire for reading and straight
      ahead distance. Failure was defined as worsening or no change in diplopia. For
      both successes and failures, mean Adult Strabismus-20 scores were compared before
      prism and in prism correction. Each of the 4 Adult Strabismus-20 domains (self
      perception, interactions, reading function, and general function) was analyzed
      separately. RESULTS: Twenty-three of 34 (68%) were successes and 11 (32%) were
      failures. For successes, reading function improved from 57 +/- 27 (SD) before
      prism to 69 +/- 27 in-prism correction (difference 12 +/- 20, 95% CI 3.2-20.8, P
      = .02) and general function improved from 66 +/- 25 to 80 +/- 18 (difference 14
      +/- 22, 95% CI 5.0-23.6, P = .003). Self-perception and interaction domains
      remained unchanged (P > .2). For failures there was no significant change in
      Adult Strabismus-20 score on any domain (P > .4). CONCLUSIONS: Successful
      correction of diplopia with prism is associated with improvement in strabismus
      specific HRQOL, specifically reading function and general function.

PMID- 24561172
TI  - Evaluation of dry eye and meibomian gland dysfunction after cataract surgery.
AB  - PURPOSE: To evaluate dry eye and meibomian gland dysfunction after cataract
      surgery. DESIGN: Prospective observational case series. METHODS: We studied 58
      eyes of 48 patients who underwent phacoemulsification and evaluated them
      preoperatively and at 1 month and 3 months postoperatively. Ocular symptom
      scores, lid margin abnormalities, superficial punctate keratopathies (SPKs), tear
      film break-up time (TBUT), Schirmer test, lower tear meniscus height, depth, and
      area using Fourier domain optical coherence tomography, meibum expressibility and
      images of the meibomian glands using meibography were measured. RESULTS: The
      ocular symptom scores were worse at 1 month and 3 months postoperatively (P <
      0.001 and P < 0.001, respectively). Lid margin abnormalities were significantly
      increased (P < 0.001 and P < 0.001, respectively) and TBUT decreased
      postoperatively (P < 0.001 and P < 0.001, respectively). Meibum expressibility
      decreased at 3 months postoperatively (P = 0.016); however, meibography score,
      SPK, lower tear meniscus height, depth and area and the Schirmer test did not
      change significantly postoperatively (all P values >0.05). CONCLUSION: Meibomian
      gland function may be altered without accompanying structural changes after
      cataract surgery.

PMID- 24561173
TI  - Long-term effects of multiple intravitreal antivascular endothelial growth factor
      injections on intraocular pressure.
AB  - PURPOSE: To evaluate long-term effects of multiple intravitreal antivascular
      endothelial growth factor (VEGF) injections on intraocular pressure (IOP) in eyes
      with neovascular age-related macular degeneration (AMD) or retinal vein occlusion
      (RVO). DESIGN: Retrospective cohort study. METHODS: This study enrolled patients
      who underwent multiple (more than 3) intravitreal anti-VEGF injections and who
      were followed for more than 12 months after their last injection. IOP elevation
      was defined as an increase of 5 mm Hg over the baseline measurement on 2
      consecutive visits. The frequency of IOP elevation was determined. A hazard ratio
      of each putative risk factor for IOP elevation was calculated using the Cox
      proportional hazard model for all participants, incorporating underlying disease
      as a covariate, as well as for each cohort. RESULTS: Included in the analysis
      were 629 eyes with neovascular AMD and 95 eyes with RVO. Twenty eyes with
      neovascular AMD (3.0%) and 7 eyes with RVO (7.4%) experienced IOP elevation after
      multiple anti-VEGF injections, with an overall incidence of 3.7%. In the Cox
      proportional hazard analysis of total participants, a diagnosis of RVO (3.424, P
      = 0.005), a history of glaucoma (8.441, P = 0.001), and low baseline IOP (0.865,
      P = 0.040) were all significant risk factors for IOP elevation after multiple
      anti-VEGF injections. CONCLUSION: A history of multiple intravitreal anti-VEGF
      injections was not a significant risk factor for IOP elevation in our study. IOP
      elevation was more common in eyes with RVO than with AMD after anti-VEGF
      injection.

PMID- 24561174
TI  - [Troponin i in the emergency department of a tertiary hospital: Appropriate use
      is made?].

PMID- 24561175
TI  - Comparison of reconstructive procedures for glenoid bone loss associated with
      recurrent anterior shoulder instability.
AB  - HYPOTHESIS: A tibial plafond allograft, iliac crest allograft, and coracoid
      autograft in a congruent arc Latarjet reconstruction better restore radius of
      curvature, depth, and surface area for glenoid bone loss in recurrent instability
      compared with the coracoid autograft in a standard Latarjet reconstruction for
      anteroinferior glenoid bone loss of the shoulder. METHODS: Three-dimensional
      shoulder models were generated from bilateral computed tomography scans in 15
      patients, who were a mean (standard deviation [SD]) age of 23 (7.7) years, with
      recurrent anterior shoulder instability and known glenoid bone loss. The surface
      areas of the glenoid in the involved and contralateral normal shoulder were
      measured. Virtual surgery was then performed using standard and congruent arc
      Latarjet reconstruction, tibial plafond, and iliac crest allografts. Grafts were
      optimally positioned to restore articular congruity and defect fill. Radius of
      curvature and restoration of glenoid depth were compared with the contralateral
      glenoid. RESULTS: Glenoid surface area (11.04% [6.95% SD]) and depth (0.75 [0.57
      SD] vs 1.44 [0.65 SD] mm) were significantly reduced (P < .012) in the injured
      glenoid. The mean (SD) coronal plane radius of curvature of the congruent arc
      Latarjet reconstruction (60.3 [39.0 SD] mm) more closely matched the radius of
      curvature of the injured glenoid (67.5 [33.2 SD] mm) compared with the other
      grafts. Restored glenoid depth was greater in the tibial plafond (1.8 [1.1 SD]
      mm) and iliac crest (2.0 [0.6 SD] mm) allografts compared with other grafts (P <
      .002). CONCLUSION: Congruent arc Latarjet reconstruction more closely restores
      native glenoid coronal radius of curvature, whereas tibial plafond and iliac
      crest allografts more adequately restore depth compared with standard Latarjet
      reconstruction.

PMID- 24561176
TI  - Clinical and radiographic results of cementless reverse total shoulder
      arthroplasty: a comparative study with 2 to 5 years of follow-up.
AB  - BACKGROUND: Most studies of reverse total shoulder arthroplasty (RTSA) involve
      cemented humeral stems. To our knowledge, this is the first study to compare the
      results of cementless RTSA, using a porous-coated stem designed for uncemented
      fixation, with cemented RTSA. METHODS: A prospective database of patients
      undergoing RTSA was retrospectively reviewed for patients with a diagnosis of
      cuff tear arthropathy or severe rotator cuff deficiency with minimum 2-year
      follow-up. Of these, 37 patients had cemented RTSA and 64 patients had cementless
      RTSA. Outcome measures included Constant-Murley scores, American Shoulder and
      Elbow Surgeons scores, visual analog pain scale scores, range of motion, patient
      satisfaction, and radiographic evidence of complication. RESULTS: Compared with
      preoperative values, both cohorts demonstrated significant improvements (P < .01)
      in all functional scores, active forward elevation, and active internal rotation.
      There was no significant difference (P > .05) in comparing the changes in these
      values after surgery between the cemented and cementless cohorts. On radiographic
      evaluation, there was no evidence of loosening or humeral components "at risk" of
      loosening in either group. There was no significant difference (P = 1.0) in the
      incidence of humeral component radiolucent lines between the cemented and
      uncemented cohorts. There was no significant difference (P = .30) in the
      incidence of scapular notching between the cemented (n = 8) and uncemented (n =
      10) cohorts. CONCLUSION: Cementless fixation of a porous-coated RTSA humeral stem
      provides clinical and radiographic outcomes equivalent to those of cemented stems
      at minimum 2-year follow-up. With advantages such as simplified operative
      technique, no cement-related complications, greater ease of revision, and long
      lasting biologic fixation, uncemented fixation may provide several benefits over
      cemented fixation.

PMID- 24561177
TI  - Prevalence of and risk factors for shoulder osteoarthritis in Japanese middle
      aged and elderly populations.
AB  - BACKGROUND: The purpose of this study was to determine the prevalence of shoulder
      osteoarthritis (OA) in populations older than 40 years and to examine risk
      factors and the relationship with shoulder function. METHODS: The respondents in
      this study consisted of 541 patients who underwent general medical examinations
      in April 2012 as residents of a single village. The mean age was 65.2 +/- 11.0
      years (range, 40-89 years), and 341 (63.0%) of the respondents were women.
      Anteroposterior radiographs of the bilateral shoulder joints were obtained, and
      the subjects were classified into 3 groups (non-OA, mild OA, and moderate-severe
      OA) according to the Samilson-Prieto method. With respect to risk factors for
      shoulder OA, a logistic regression analysis was performed. RESULTS: Shoulder OA
      was detected in 17.4% (94 of 541) of the patients. The incidence of OA in both
      shoulders was 3.1% (17 of 541), and the prevalence of shoulder OA among the
      respondents 65 years of age or older (20.3%) was significantly higher than that
      observed among the respondents younger than 65 years (11.1%). The risk of
      shoulder OA increased according to age, with an odds ratio of 5.59 in the
      respondents 60 to 69 years of age (P = .027), 11.59 in the respondents 70 to 79
      years of age (P = .004), and 10.77 in the respondents 80 years of age and older
      (P = .004). CONCLUSIONS: The prevalence of shoulder OA was 17.4%, and the risk
      factor for shoulder OA was age.

PMID- 24561178
TI  - Acrolein relaxes mouse isolated tracheal smooth muscle via a TRPA1-dependent
      mechanism.
AB  - Airway sensory C-fibres express TRPA1 channels which have recently been
      identified as a key chemosensory receptor for acrolein, a toxic and highly
      prevalent component of smoke. TRPA1 likely plays an intermediary role in
      eliciting a range of effects induced by acrolein including cough and neurogenic
      inflammation. Currently, it is not known whether acrolein-induced activation of
      TRPA1 produces other airway effects including relaxation of mouse airway smooth
      muscle. The aims of this study were to examine the effects of acrolein on airway
      smooth muscle tone in mouse isolated trachea, and to characterise the cellular
      and molecular mechanisms underpinning the effects of acrolein. Isometric tension
      recording studies were conducted on mouse isolated tracheal segments to
      characterise acrolein-induced relaxation responses. Release of the relaxant PGE2
      was measured by EIA to examine its role in the response. Use of selective
      antagonists/inhibitors permitted pharmacological characterisation of the
      molecular and cellular mechanisms underlying this relaxation response. Acrolein
      induced dose-dependent relaxation responses in mouse isolated tracheal segments.
      Importantly, these relaxation responses were significantly inhibited by the TRPA1
      antagonists AP-18 and HC-030031, an NK1 receptor antagonist RP-67580, and the EP2
      receptor antagonist PF-04418948, whilst completely abolished by the non-selective
      COX inhibitor indomethacin. Acrolein also caused rapid PGE2 release which was
      suppressed by HC-030031. In summary, acrolein induced a novel bronchodilator
      response in mouse airways. Pharmacologic studies indicate that acrolein-induced
      relaxation likely involves interplay between TRPA1-expressing airway sensory C
      fibres, NK1 receptor-expressing epithelial cells, and EP2-receptor expressing
      airway smooth muscle cells.

PMID- 24561179
TI  - A physiologically based kinetic (PBK) model describing plasma concentrations of
      quercetin and its metabolites in rats.
AB  - Biological activities of flavonoids in vivo are ultimately dependent on the
      systemic bioavailability of the aglycones as well as their metabolites. In the
      present study, a physiologically based kinetic (PBK) model was developed to
      predict plasma concentrations of the flavonoid quercetin and its metabolites and
      to tentatively identify the regiospecificity of the major circulating
      metabolites. The model was developed based on in vitro metabolic parameters and
      by fitting kinetic parameters to literature available in vivo data. Both exposure
      to quercetin aglycone and to quercetin-4'-O-glucoside, for which in vivo data
      were available, were simulated. The predicted plasma concentrations of different
      metabolites adequately matched literature reported plasma concentrations of these
      metabolites in rats exposed to 4'-O-glucoside. The bioavailability of aglycone
      was predicted to be very low ranging from 0.004%-0.1% at different oral doses of
      quercetin or quercetin-4'-O-glucoside. Glucuronidation was a crucial pathway that
      limited the bioavailability of the aglycone, with 95-99% of the dose being
      converted to monoglucuronides within 1.5-2.5h at different dose levels ranging
      from 0.1 to 50mg/kg bw quercetin or quercetin-4'-O-glucoside. The fast metabolic
      conversion to monoglucuronides allowed these metabolites to further conjugate to
      di- and tri-conjugates. The regiospecificity of major circulating metabolites was
      observed to be dose-dependent. As we still lack in vivo kinetic data for many
      flavonoids, the developed model has a great potential to be used as a platform to
      build PBK models for other flavonoids as well as to predict the kinetics of
      flavonoids in humans. 

PMID- 24561180
TI  - Isolation, synthesis and characterization of omega-TRTX-Cc1a, a novel tarantula
      venom peptide that selectively targets L-type Cav channels.
AB  - Spider venoms are replete with peptidic ion channel modulators, often with novel
      subtype selectivity, making them a rich source of pharmacological tools and drug
      leads. In a search for subtype-selective blockers of voltage-gated calcium (CaV)
      channels, we isolated and characterized a novel 39-residue peptide, omega-TRTX
      Cc1a (Cc1a), from the venom of the tarantula Citharischius crawshayi (now
      Pelinobius muticus). Cc1a is 67% identical to the spider toxin omega-TRTX-Hg1a,
      an inhibitor of CaV2.3 channels. We assembled Cc1a using a combination of Boc
      solid-phase peptide synthesis and native chemical ligation. Oxidative folding
      yielded two stable, slowly interconverting isomers. Cc1a preferentially inhibited
      Ba(2+) currents (IBa) mediated by L-type (CaV1.2 and CaV1.3) CaV channels
      heterologously expressed in Xenopus oocytes, with half-maximal inhibitory
      concentration (IC50) values of 825nM and 2.24MUM, respectively. In rat dorsal
      root ganglion neurons, Cc1a inhibited IBa mediated by high voltage-activated CaV
      channels but did not affect low voltage-activated T-type CaV channels. Cc1a
      exhibited weak activity at NaV1.5 and NaV1.7 voltage-gated sodium (NaV) channels
      stably expressed in mammalian HEK or CHO cells, respectively. Experiments with
      modified Cc1a peptides, truncated at the N-terminus (DeltaG1-E5) or C-terminus
      (DeltaW35-V39), demonstrated that the N- and C-termini are important for voltage
      gated ion channel modulation. We conclude that Cc1a represents a novel
      pharmacological tool for probing the structure and function of L-type CaV
      channels. 

PMID- 24561181
TI  - Mammalian flavin-containing monooxygenase (FMO) as a source of hydrogen peroxide.
AB  - Flavin-containing monooxygenase (FMO) oxygenates drugs/xenobiotics containing a
      soft nucleophile through a C4a hydroperoxy-FAD intermediate. Human FMOs 1, 2 and
      3, expressed in Sf9 insect microsomes, released 30-50% of O2 consumed as H2O2
      upon addition of NADPH. Addition of substrate had little effect on H2O2
      production. Two common FMO2 (the major isoform in the lung) genetic
      polymorphisms, S195L and N413K, were examined for generation of H2O2. FMO2 S195L
      exhibited higher "leakage", producing much greater amounts of H2O2, than
      ancestral FMO2 (FMO2.1) or the N413K variant. S195L was distinct in that H2O2
      generation was much higher in the absence of substrate. Addition of superoxide
      dismutase did not impact H2O2 release. Catalase did not reduce levels of H2O2
      with either FMO2.1 or FMO3 but inhibited H2O2 generated by FMO2 allelic variants
      N413K and S195L. These data are consistent with FMO molecular models. S195L
      resides in the GxGxSG/A NADP(+) binding motif, in which serine is highly
      conserved (76/89 known FMOs). We hypothesize that FMO, especially allelic
      variants such as FMO2 S195L, may enhance the toxicity of xenobiotics such as
      thioureas/thiocarbamides both by generation of sulfenic and sulfinic acid
      metabolites and enhanced release of reactive oxygen species (ROS) in the form of
      H2O2.

PMID- 24561182
TI  - Left ventricular longitudinal strain by speckle-tracking echocardiography is
      associated with treatment-requiring cardiac allograft rejection.
AB  - BACKGROUND: Noninvasive detection of rejection is a major objective in the
      management of heart transplant recipients. METHODS AND RESULTS: To investigate
      the utility of 2-dimensional speckle-tracking echocardiography (2D-STE), we
      retrospectively evaluated 160 sets of endomyocardial biopsies and echocardiograms
      from 59 asymptomatic heart transplant recipients. Conventional International
      Society for Heart and Lung Transplantation grade 1B or higher rejection was
      considered as treatment-requiring rejection (group R), whereas International
      Society for Heart and Lung Transplantation grade 0 or 1A was classified as group
      Non-R. Left ventricular global longitudinal strain (GLS), global circumferential
      strain, and global radial strain were assessed by 2D-STE. Twenty-five specimens
      were classified into group R. GLS was significantly associated with treatment
      requiring rejection, whereas neither global radial strain nor global
      circumferential strain were. Lower GLS remained significantly associated with an
      increased risk of treatment-requiring rejection (odds ratio, 1.15 [95% CI, 1.01
      1.30]; P=0.03) even in multivariate analysis. GLS with the absolute value of less
      than 14.8% showed sensitivity and specificity of 64% and 63%, respectively, for
      detection of treatment-requiring rejection. CONCLUSION: The 2D-STE-derived left
      ventricular GLS was associated with treatment-requiring rejection. Two
      dimensional STE might be useful as a noninvasive supplemental tool for monitoring
      heart transplant recipients for possible treatment-requiring rejection.

PMID- 24561184
TI  - Tim-3 signaling pathway as a novel negative mediator in lipopolysaccharide
      induced endotoxic shock.
AB  - Sepsis is a complex clinical condition caused by a dysregulated immune response
      to an infection. However, the mechanism by which our immune system controls this
      amplified inflammation is largely unknown. In this study, we investigated whether
      Tim-3 pathway could serve as a negative mediator in lipopolysaccharide (LPS)
      induced endotoxic shock. Our results showed that Tim-3 was expressed on CD4(+) T
      cells, CD8(+) T cells, and NK cells, and was significantly increased in the
      peritoneal cavity of septic mice. Tim-3 acted as a marker of immune exhaustion
      and Tim-3-positive T cells and NK cells had a lower interferon (IFN)-gamma
      production. Furthermore, blockade of Tim-3 pathway significantly accelerated
      mortality in septic mice, while activation of this pathway prolonged survival
      time. In vitro administration of Tim-3 blocking antibody restored the release of
      IFN-gamma from splenocytes and decreased splenocyte apoptosis, and increased
      levels of IFN-gamma and tumor necrosis factor (TNF)-alpha were also detected in
      septic mice at 24h post in vivo administration of the antibody. In contrast,
      activation of Tim-3 pathway prevented cell proliferation. Thus, Tim-3 signaling
      pathway acts as a novel negative mediator in LPS-induced endotoxic shock and
      could be a potential therapeutic target for the treatment of sepsis. 

PMID- 24561185
TI  - Reducing respiratory effect in motion correction for EPI images with sequential
      slice acquisition order.
AB  - Motion correction is critical for data analysis of fMRI time series. Most motion
      correction algorithms treat the head as a rigid body. Respiration of the subject,
      however, can alter the static magnetic field in the head and result in motion
      like slice shifts for echo planar imaging (EPI). The delay of acquisition between
      slices causes a phase difference in respiration so that the shifts vary with
      slice positions. To characterize the effect of respiration on motion correction,
      we acquired fast sampled fMRI data using multi-band EPI and then simulated
      different acquisition schemes. Our results indicated that respiration introduces
      additional noise after motion correction. The signal variation between volumes
      after motion correction increases when the effective TR increases from 675ms to
      2025ms. This problem can be corrected if slices are acquired sequentially. For
      EPI with a sequential acquisition scheme, we propose to divide the image volumes
      into several segments so that slices within each segment are acquired close in
      time and then perform motion correction on these segments separately. We
      demonstrated that the temporal signal-to-noise ratio (TSNR) was increased when
      the motion correction was performed on the segments separately rather than on the
      whole image. This enhancement of TSNR was not evenly distributed across the
      segments and was not observed for interleaved acquisition. The level of increase
      was higher for superior slices. On superior slices the percentage of TSNR gain
      was comparable to that using image based retrospective correction for respiratory
      noise. Our results suggest that separate motion correction on segments is highly
      recommended for sequential acquisition schemes, at least for slices distal to the
      chest. 

PMID- 24561183
TI  - Leptin stimulates sympathetic axon outgrowth.
AB  - The neurohormone leptin regulates energy homeostasis. Circulating levels of
      leptin secreted by adipose tissue act on hypothalamic neurons in the brain
      leading to decreased appetite and increased energy expenditure. Although leptin
      signaling in the central nervous system (CNS) is fundamental to its ability to
      regulate the body's metabolic balance, leptin also has a variety of effects in
      many peripheral tissues including the heart, the liver, and the sympathetic
      nervous system. Leptin stimulation of the hypothalamus can stimulate glucose
      uptake via the sympathetic nervous system in heart, muscle, and brown adipose
      tissue. Leptin receptors (Ob-Rb) are also expressed by peripheral sympathetic
      neurons, but their functional role is not clear. In this study, we found that
      leptin stimulates axonal growth of both adult and neonatal sympathetic neurons in
      vitro. Leptin stimulates acute activation of the transcription factor STAT3 via
      phosphorylation of tyrosine 705. STAT3 phosphorylation is required for leptin
      stimulated sympathetic axon outgrowth. Thus, circulating levels of leptin may
      enhance sympathetic nerve innervation of peripheral tissues. 

PMID- 24561186
TI  - Phloem mobility and translocation of fluorescent conjugate containing glucose and
      NBD in castor bean (Ricinus communis).
AB  - Phloem mobility is an important factor for long-distance transport of systemic
      pesticides in plants. Our previous study revealed that a fluorescent glucose
      insecticide conjugate, N-{3-cyano-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4
      iodo-1H-pyrazol-5-yl}-N-{[1-(beta-D-glucopyranosyl)-1H-1,2,3-triazole-4
      yl]methyl}-N-{[1-((N-(7-nitrobenz-2-oxa-1,3-diazole-4-amine))-propyl)-1H-1,2,3
      triazole-4-yl]methyl}amine (IPGN), can be transported in tobacco cells. Several
      studies have also indicated that glucose moieties can guide the conjugates into
      plant cells. In this study, we investigated the phloem mobility of IPGN within
      castor bean seedlings. Cotyledon uptake experiment results show that IPGN could
      enter the phloem of the mid-veins of cotyledons. The results of further
      quantitative analysis show that IPGN was present in small amounts in the phloem
      sap despite the inconsistencies of physicochemical properties with diffusion
      through the plasma membrane. Its concentration in the phloem sap (about 370nM at
      5h) was much lower than that in the incubation medium (100MUM), which suggests
      that IPGN exhibited weak phloem mobility. After the leaves of Ricinus plantlets
      were treated with IPGN, green fluorescence could be observed in the phloem of the
      petioles, bud apical nodes, bud mid-veins, and mid-veins of the untreated leaves.
      The localization of the fluorescent conjugate at various levels of Ricinus
      plantlets indicates that it was translocated at a distance to sink organs via
      sieve tubes. The results proved that introducing a glucose group is a feasible
      approach to modify non-phloem-mobile pesticides and produce phloem-mobile
      pesticides.

PMID- 24561188
TI  - Property content guides children's memory for social learning episodes.
AB  - How do children's interpretations of the generality of learning episodes affect
      what they encode? In the present studies, we investigated the hypothesis that
      children encode distinct aspects of learning episodes containing generalizable
      and non-generalizable properties. Two studies with preschool (N=50) and young
      school-aged children (N=49) reveal that their encoding is contingent on the
      generalizability of the property they are learning. Children remembered
      generalizable properties (e.g., morphological or normative properties) more than
      non-generalizable properties (e.g., historical events or preferences).
      Conversely, they remembered category exemplars associated with non-generalizable
      properties more than category exemplars associated with generalizable properties.
      The findings highlight the utility of remembering distinct aspects of social
      learning episodes for children's future generalization. 

PMID- 24561187
TI  - Semantic memory: distinct neural representations for abstractness and valence.
AB  - The hypothesis that abstract words are grounded in emotion has been supported by
      behavioral research and corpus studies of English words. A recent neuroimaging
      study reported that a single brain region, the rostral anterior cingulate cortex
      (rACC), is responsive to abstract words, and is furthermore modulated by the
      emotional valence. This finding is surprising because the rACC is not commonly
      associated with semantic processing. It is possible that the effects observed
      were driven not by abstractness, but rather by valence, since the abstract words
      used in that study were significantly more emotional than the concrete words. We
      tested this hypothesis by presenting participants with words that were
      abstract/concrete, as well as emotionally valenced/neutral in a 2*2 factorial
      design. Activations to emotional words overlapped with both abstract and concrete
      activations throughout the brain. An ROI analysis revealed that the rACC was
      responsive to valence, not abstractness, when concreteness and valence
      unconfounded. 

PMID- 24561189
TI  - Categorical perception of tactile distance.
AB  - The tactile surface forms a continuous sheet covering the body. And yet, the
      perceived distance between two touches varies across stimulation sites. Perceived
      tactile distance is larger when stimuli cross over the wrist, compared to when
      both fall on either the hand or the forearm. This effect could reflect a
      categorical distortion of tactile space across body-part boundaries (in which
      stimuli crossing the wrist boundary are perceptually elongated) or may simply
      reflect a localised increased in acuity surrounding anatomical landmarks (in
      which stimuli near the wrist are perceptually elongated). We tested these two
      interpretations across two experiments, by comparing a well-documented bias to
      perceive mediolateral tactile distances across the forearm/hand as larger than
      proximodistal ones along the forearm/hand at three different sites (hand, wrist,
      and forearm). According to the 'categorical' interpretation, tactile distances
      should be elongated selectively in the proximodistal axis thus reducing the
      anisotropy. According to the 'localised acuity' interpretation, distances will be
      perceptually elongated in the vicinity of the wrist regardless of orientation,
      leading to increased overall size without affecting anisotropy. Consistent with
      the categorical account, we found a reduction in the magnitude of anisotropy at
      the wrist, with no evidence of a corresponding localised increase in precision.
      These findings demonstrate that we reference touch to a representation of the
      body that is categorically segmented into discrete parts, which consequently
      influences the perception of tactile distance. 

PMID- 24561190
TI  - Scrutinizing visual images: the role of gaze in mental imagery and memory.
AB  - Gaze was monitored by use of an infrared remote eye-tracker during perception and
      imagery of geometric forms and figures of animals. Based on the idea that gaze
      prioritizes locations where features with high information content are visible,
      we hypothesized that eye fixations should focus on regions that contain one or
      more local features that are relevant for object recognition. Most importantly,
      we predicted that when observers looked at an empty screen and at the same time
      generated a detailed visual image of what they had previously seen, their gaze
      would probabilistically dwell within regions corresponding to the original
      positions of salient features or parts. Correlation analyses showed positive
      relations between gaze's dwell time within locations visited during perception
      and those in which gaze dwelled during the imagery generation task. Moreover, the
      more faithful an observer's gaze enactment, the more accurate was the observer's
      memory, in a separate test, of the dimension or size in which the forms had been
      perceived. In another experiment, observers saw a series of pictures of animals
      and were requested to memorize them. They were then asked later, in a recall
      phase, to answer a question about a property of one of the encoded forms; it was
      found that, when retrieving from long-term memory a previously seen picture, gaze
      returned to the location of the part probed by the question. In another
      experimental condition, the observers were asked to maintain fixation away from
      the original location of the shape while thinking about the answer, so as to
      interfere with the gaze enactment process; such a manipulation resulted in
      measurable costs in the quality of memory. We conclude that the generation of
      mental images relies upon a process of enactment of gaze that can be beneficial
      to visual memory. 

PMID- 24561191
TI  - Structural insights into conserved L-arabinose metabolic enzymes reveal the
      substrate binding site of a thermophilic L-arabinose isomerase.
AB  - Structural genomics demonstrates that despite low levels of structural similarity
      of proteins comprising a metabolic pathway, their substrate binding regions are
      likely to be conserved. Herein based on the 3D-structures of the alpha/beta-fold
      proteins involved in the ara operon, we attempted to predict the substrate
      binding residues of thermophilic Geobacillus stearothermophilus L-arabinose
      isomerase (GSAI) with no 3D-structure available. Comparison of the structures of
      L-arabinose catabolic enzymes revealed a conserved feature to form the substrate
      binding modules, which can be extended to predict the substrate binding site of
      GSAI (i.e., D195, E261 and E333). Moreover, these data implicated that proteins
      in the l-arabinose metabolic pathway might retain their substrate binding niches
      as the modular structure through conserved molecular evolution even with totally
      different structural scaffolds.

PMID- 24561192
TI  - USP22 is a positive regulator of NFATc2 on promoting IL2 expression.
AB  - Nuclear factor of activated T cells (NFAT) is an important regulator of T cell
      activation. However, the molecular mechanism whereby NFATc2 regulates IL2
      transcription is not fully understood. In this study, we showed that ubiquitin
      specific protease 22 (USP22), known as a cancer stem cell marker, specifically
      interacted with and deubiquitinated NFATc2. USP22 stabilized NFATc2 protein
      levels, which required its deubiquitinase activity. Consistent with these
      observations, depletion of USP22 in T cells reduced the expression of IL2, which
      is a cytokine that signifies T effector cell activation. Our findings thus unveil
      a previously uncharacterized positive regulator of NFATc2, suggesting that
      targeting the deubiquitinase activity of USP22 could have therapeutic benefit to
      control IL2 expression and T cell function. 

PMID- 24561193
TI  - A hIAPP-derived all-D-amino-acid inhibits hIAPP fibrillation efficiently at
      membrane surface by targeting alpha-helical oligomeric intermediates.
AB  - A variety of peptides and peptide derivatives have been constructed using the
      "beta-sheet core segment" of amyloid proteins as inhibitors of amyloidogenic
      fibrillation. A novel all-D-amino-acid from hIAPP beta-sheet core segment (hIAPP
      22-27) is demonstrated to inhibit hIAPP fibril formation efficiently both at the
      phospholipid membrane and in bulk solution. The inhibitor terminates hIAPP
      aggregation to the alpha-helical oligomeric intermediates at the membrane
      surface, whereas it stops the aggregation at the stage of beta-sheet oligomeric
      intermediates in bulk solution. This is the first evidence that the inhibition
      mechanism of the inhibitor at membrane surface is significantly different from
      that in bulk solution.

PMID- 24561194
TI  - 42- and 63-bp anti-MDR1-siRNAs bearing 2'-OMe modifications in nuclease-sensitive
      sites induce specific and potent gene silencing.
AB  - DsRNAs longer than 30bp induce interferon response and global changes in gene
      expression profile in mammalians. 21bp siRNA and 25/27bp dsiRNA acting via RNA
      interference mechanism are used for specific gene silencing in this class of
      organisms. We designed selectively 2'-O-methyl-modified 42 and 63bp anti-MDR1
      siRNAs that silence the expression of P-glycoprotein and restore the sensitivity
      of drug-resistant cancer cells to cytostatic more efficiently than canonical 21bp
      siRNAs. We also show that they act in a Dicer-independent mode and are devoid of
      immunostimulating properties. Our findings suggest that 42 and 63bp siRNAs could
      be used as potential therapeutics. 

PMID- 24561195
TI  - Expression of synaptopodin in endothelial cells exposed to laminar shear stress
      and its role in endothelial wound healing.
AB  - We examined the hypothesis that certain actin binding proteins might be
      upregulated by laminar shear stress (LSS) and could contribute to endothelial
      wound healing. Analysis of mRNA expression profiles of human umbilical vein
      endothelial cells under static and LSS-exposed conditions provided a list of LSS
      induced actin binding proteins including synaptopodin (SYNPO) whose endothelial
      expression has not been previously reported. Additional studies demonstrated that
      SYNPO is a key mediator of endothelial wound healing because small interfering
      RNA-mediated suppression of SYNPO attenuated wound closure under LSS whereas
      overexpression of exogenous SYNPO enhanced endothelial wound closure in the
      absence of LSS. This study suggests that LSS-induced actin binding proteins
      including SYNPO may play a critical role in the endothelial wound healing
      stimulated by LSS. 

PMID- 24561197
TI  - Splicing inhibition induces gene expression through canonical NF-kappaB pathway
      and extracellular signal-related kinase activation.
AB  - Splicing, a process for mRNA maturation, is essential for correct gene expression
      after transcription. However, recent studies also suggest that splicing affects
      transcription, but its mechanism remains elusive. We previously reported that
      treatment with spliceostatin A (SSA), a specific splicing inhibitor targeting the
      splicing factor SF3b, leads to transcriptional activation of a small subset of
      genes. To investigate the underlying mechanism we utilized luciferase reporters
      driven by the Interleukin 8 (IL-8) and cytomegalovirus (CMV) promoters, as both
      recruit a similar set of transcription factors. We also found that SSA treatment
      led to increased extracellular signal-regulated protein kinase (ERK) activity and
      that chemical inhibition of ERK also led to decreased promoter activation.
      Systematic deletion studies suggested that NF-kappaB activation is mainly
      responsible for SSA-induced promoters activation. 

PMID- 24561198
TI  - Anti-cancer drug KP1019 modulates epigenetics and induces DNA damage response in
      Saccharomyces cerevisiae.
AB  - KP1019 comprises a class of ruthenium compounds having promising anticancer
      activity. Here, we investigated the molecular targets of KP1019 using
      Saccharomyces cerevisiae as a model organism. Our results revealed that in the
      absence of the N-terminal tail of histone H3, the growth inhibitory effect of
      KP1019 was markedly enhanced. Furthermore, H3K56A or rtt109Delta mutants exhibit
      hypersensitivity for KP1019. Moreover, KP1019 evicts histones from the
      mononucleosome and interacts specifically with histone H3. We have also shown
      that KP1019 treatment causes induction of Ribonucleotide Reductase (RNR) genes
      and degradation of Sml1p. Our results also suggest that DNA damage induced by
      KP1019 is primarily repaired through double-strand break repair (DSBR). In
      summary, KP1019 targets histone proteins, with important consequences for DNA
      damage responses and epigenetics. 

PMID- 24561196
TI  - Mix and match: investigating heteromeric and heterotypic gap junction channels in
      model systems and native tissues.
AB  - This review is based in part on a roundtable discussion session: "Physiological
      roles for heterotypic/heteromeric channels" at the 2013 International Gap
      Junction Conference (IGJC 2013) in Charleston, South Carolina. It is well
      recognized that multiple connexins can specifically co-assemble to form mixed gap
      junction channels with unique properties as a means to regulate intercellular
      communication. Compatibility determinants for both heteromeric and heterotypic
      gap junction channel formation have been identified and associated with specific
      connexin amino acid motifs. Hetero-oligomerization is also a regulated process;
      differences in connexin quality control and monomer stability are likely to play
      integral roles to control interactions between compatible connexins. Gap
      junctions in oligodendrocyte:astrocyte communication and in the cardiovascular
      system have emerged as key systems where heterotypic and heteromeric channels
      have unique physiologic roles. There are several methodologies to study
      heteromeric and heterotypic channels that are best applied to either heterologous
      expression systems, native tissues or both. There remains a need to use and
      develop different experimental approaches in order to understand the prevalence
      and roles for mixed gap junction channels in human physiology. 

PMID- 24561199
TI  - Characterization of the effects of phosphorylation by CK2 on the structure and
      binding properties of human HP1beta.
AB  - Proteins of the Heterochromatin Protein 1 (HP1) family are regulators of
      chromatin structure and genome function in eukaryotes. Post-translational
      modifications expand the repertoire of the chemical diversity of HP1 proteins and
      regulate their activity. Here, we investigated the effect of phosphorylation by
      Casein kinase 2 (CK2) on the structure, dynamics and binding activity of human
      HP1beta. We show that Ser89 in the hinge region is the most effective substrate,
      followed by Ser175 at the C-terminal tail. Phosphorylation at these sites results
      in localized conformational changes in HP1beta that do not compromise the ability
      of the protein to bind chromatin. 

PMID- 24561201
TI  - Mislocalization of K+ channels causes the renal salt wasting in EAST/SeSAME
      syndrome.
AB  - The Kir4.1/Kir5.1 channel mediates basolateral K(+) recycling in renal distal
      tubules; this process is critical for Na(+) reabsorption at the tubules.
      Mutations in Kir4.1 are associated with EAST/SeSAME syndrome, a genetic disorder
      characterized by renal salt wasting. In this study, we found that MAGI-1 anchors
      Kir4.1 channels (Kir4.1 homomer and Kir4.1/Kir5.1 heteromer) and contributes to
      basolateral K(+) recycling. The Kir4.1 A167V mutation associated with EAST/SeSAME
      syndrome caused mistrafficking of the mutant channels and inhibited their
      expression on the basolateral surface of tubular cells. These findings suggest
      mislocalization of the Kir4.1 channels contributes to renal salt wasting. 

PMID- 24561202
TI  - Acylation and cholesterol binding are not required for targeting of influenza A
      virus M2 protein to the hemagglutinin-defined budozone.
AB  - Influenza virus assembles in the budozone, a cholesterol-/sphingolipid-enriched
      ("raft") domain at the apical plasma membrane, organized by hemagglutinin (HA).
      The viral protein M2 localizes to the budozone edge for virus particle scission.
      This was proposed to depend on acylation and cholesterol binding. We show that M2
      GFP without these motifs is still transported apically in polarized cells.
      Employing FRET, we determined that clustering between HA and M2 is reduced upon
      disruption of HA's raft-association features (acylation, transmembranous VIL
      motif), but remains unchanged with M2 lacking acylation and/or cholesterol
      binding sites. The motifs are thus irrelevant for M2 targeting in cells. 

PMID- 24561200
TI  - Deregulation of cell signaling in cancer.
AB  - Oncogenic mutations disrupt the regulatory circuits that govern cell function,
      enabling tumor cells to undergo de-regulated mitogenesis, to resist to pro
      apoptotic insults, and to invade through tissue boundaries. Cancer cell biology
      has played a crucial role in elucidating the signaling mechanisms by which
      oncogenic mutations sustain these malignant behaviors and thereby in identifying
      rational targets for cancer drugs. The efficacy of such targeted therapies
      illustrate the power of a reductionist approach to the study of cancer. 

PMID- 24561203
TI  - Hot spots in apolipoprotein A-II misfolding and amyloidosis in mice and men.
AB  - ApoA-II is the second-major protein of high-density lipoproteins. C-terminal
      extension in human apoA-II or point substitutions in murine apoA-II cause
      amyloidosis. The molecular mechanism of apolipoprotein misfolding, from the
      native predominantly alpha-helical conformation to cross-beta-sheet in amyloid,
      is unknown. We used 12 sequence-based prediction algorithms to identify two ten
      residue segments in apoA-II that probably initiate beta-aggregation. Previous
      studies of apoA-II fragments experimentally verify this prediction. Together,
      experimental and bioinformatics studies explain why the C-terminal extension in
      human apoA-II causes amyloidosis and why, unlike murine apoA-II, human apoA-II
      normally does not cause amyloidosis despite its unusually high sequence
      propensity for beta-aggregation. 

PMID- 24561205
TI  - CTCF-mediated reduction of vigilin binding affects the binding of HP1alpha to the
      satellite 2 locus.
AB  - CCCTC-binding factor (CTCF) has been implicated in numerous aspects of chromosome
      biology, and vigilin, a multi-KH-domain protein, participates in heterochromatin
      formation and chromosome segregation. We previously showed that CTCF interacts
      with vigilin. Here, we show that human vigilin, but not CTCF, colocalizes with
      HP1alpha on heterochromatic satellite 2 and beta-satellite repeats. CTCF up
      regulates the transcription of satellite 2, while vigilin down-regulates it.
      Vigilin depletion or CTCF overexpression reduces the binding of HP1alpha on the
      satellite 2 locus. Furthermore, overexpression of CTCF resists the loading of
      vigilin onto the satellite 2 locus. Thus CTCF may regulate vigilin behavior and
      thus indirectly influence the binding of HP1alpha to the satellite 2 locus. 

PMID- 24561204
TI  - Crystal structure of the RNA demethylase ALKBH5 from zebrafish.
AB  - ALKBH5, a member of AlkB family proteins, has been reported as a mammalian N(6)
      methyladenosine (m(6)A) RNA demethylase. Here we report the crystal structure of
      zebrafish ALKBH5 (fALKBH5) with the resolution of 1.65A. Structural
      superimposition shows that fALKBH5 is comprised of a conserved jelly-roll motif.
      However, it possesses a loop that interferes potential binding of a duplex
      nucleic acid substrate, suggesting an important role in substrate selection. In
      addition, several active site residues are different between the two known m(6)A
      RNA demethylases, ALKBH5 and FTO, which may result in their slightly different
      pathways of m(6)A demethylation. 

PMID- 24561206
TI  - Femorofemoral bypass to the deep femoral artery for limb salvage after prior
      failed percutaneous endovascular intervention.
AB  - BACKGROUND: To report the long-term results and clinical outcomes of
      femorofemoral bypass (FFB) to deep femoral artery (DFA) after failed endovascular
      attempts in treating critical limb ischemia (CLI) caused by long total occlusion
      of the unilateral iliofemoral artery. METHODS: A retrospective review was
      conducted on 82 consecutive patients (59 men, 23 women; mean age: 73.2 years),
      who presented with CLI and underwent FFB to DFA performed by a single surgeon.
      Preoperative and postoperative ankle-brachial index (ABI), runoff blood flow
      velocities, and long-term patency rates were analyzed, and the clinical and
      surgical variables influencing the graft patency were assessed. RESULTS: The mean
      ABI rose from 0.19 +/- 0.17 preoperative to 0.54 +/- 0.18 postoperative (P <
      0.001). The postoperative blood flow velocities of popliteal arteries (30.74 +/-
      11.62 cm/sec) and tibial arteries (21.36 +/- 8.59 cm/sec) were significantly
      higher than the preoperative values (13.96 +/- 7.62 cm/sec and 9.83 +/- 5.46
      cm/sec). At 1, 5, and 10 years, the primary, assisted, and secondary patency
      rates were 90.3%, 58.5%, and 12.2%; 91.9%, 66.0%, and 45.9%; and 98.4%, 85.1%,
      and 61.6%, respectively. By multivariate analysis, the graft patency rate was
      positively related with hypertension but negatively correlated with
      hypercholesterolemia and single patent tibial runoff. CONCLUSIONS: Our data
      suggest that FFB to DFA can be a safe, effective, and durable method for the
      treatment of CLI after prior failed endovascular attempts.

PMID- 24561207
TI  - Prospective randomized trial of ACUSEAL versus Vascu-Guard patching in carotid
      endarterectomy.
AB  - BACKGROUND: Multiple studies have been conducted that demonstrate the superiority
      of patch angioplasty over primary closure for carotid endarterectomy (CEA). Patch
      angioplasty with polytetrafluorethylene patches (ACUSEAL) have shown results
      comparable to patch angioplasty with saphenous vein and polyester patches. This
      is a prospective randomized study to compare the clinical outcomes of CEA using
      ACUSEAL versus bovine pericardium patching (Vascu-Guard). METHODS: Two hundred
      patients were randomized (1:1) to either ACUSEAL or Vascu-Guard patching.
      Demographic data/clinical characteristics were collected. Intraoperative
      hemostasis times and the frequency of reexploration for neck hematoma were
      recorded. All patients received immediate and 1-month postoperative duplex
      ultrasound studies, which were repeated at 6-month intervals. A Kaplan-Meier
      analysis was used to estimate the risk of restenosis and the stroke-free survival
      rates. RESULTS: The demographics were similar in both groups, except for a higher
      incidence of current smokers in the ACUSEAL group and more patients with
      congestive heart failure in the Vascu-Guard group (P = 0.02 and 0.03,
      respectively). The mean operative internal carotid artery diameter and the mean
      arteriotomy length were similar in both groups. The mean hemostasis time was 4.90
      min for ACUSEAL patching vs. 3.09 min for Vascu-Guard (P = 0.027); however, the
      mean operative times were similar for both groups (ACUSEAL 2.09 hr vs. Vascu
      Guard 2.16 hr, P = 0.669). The incidence of reexploration for neck hematoma was
      higher in the Vascu-Guard group; 6.12% vs. 1.03% (P = 0.1183). The incidence of
      perioperative ipsilateral neurologic events was 3.09% for ACUSEAL patching vs.
      1.02% for Vascu-Guard patching (P = 0.368). The mean follow-up period was 15
      months. The respective freedom from >=70% carotid restenosis at 1, 2, and 3 years
      were 100%, 100%, and 100% for ACUSEAL patching vs. 100%, 98%, and 98% for Vascu
      Guard patching (P = 0.2478). The ipsilateral stroke-free rates at 1, 2, and 3
      years were 96% for ACUSEAL and 99% for Vascu-Guard patching. CONCLUSIONS:
      Although CEA patching with ACUSEAL versus Vascu-Guard differed in hemostasis
      time, the frequency of reexploration for neck hematomas was more frequent in the
      pericardial patch group; however, only 1 patient had documented suture line
      bleeding and the surgical reexploration rate is not likely to be patch related.
      There were not any significant differences in perioperative/late neurologic
      events and late restenosis in the 2 groups.

PMID- 24561208
TI  - Effects of Ginkgo biloba extract on spinal cord ischemia-reperfusion injury in
      rats.
AB  - BACKGROUND: We aimed to assess the biochemical and histopathologic effects of
      Ginkgo biloba extract (EGb) in an ischemia-reperfusion (IR) model of spinal cord
      ischemia induced by cross-clamping of the infrarenal abdominal aorta. METHODS: A
      total of 24 Sprague-Dawley rats were divided into 3 groups as group 1: control
      (sham laparotomy), group 2: IR, and group 3: IR+EGb treatment (IR+T) group. All
      subjects were euthanized 2 days postsurgery and their spinal cords were removed.
      Tissue malondialdehyde, superoxide dismutase, glutathione (GSH), and glutathione
      peroxidase levels were measured, and the spinal cord tissue samples were examined
      histopathologically. RESULTS: No significant difference was detected in ischemia
      markers between control, IR, and IR+T groups, with the exception of GSH, which
      was significantly lower in the IR group. GSH levels in group 1 and group 3 were
      similar. The group 2 displayed significant ischemic damage to the medulla
      spinalis. This damage was less pronounced in group 3 compared with group 2 only,
      but in extent and intensity comparable with the controls. CONCLUSIONS: Although
      we were not able to demonstrate a uniform effect of EGb on biochemical markers of
      IR injury, the histopathologic data appear to show a protective effect conferred
      on the spinal cord tissue by EGb.

PMID- 24561209
TI  - Effects of cilostazol on arterial wound healing: a retrospective analysis.
AB  - BACKGROUND: The vasodilator cilostazol (Pletal((r))), a phosphodiesterase-3
      inhibitor, is approved in the United States for treatment of intermittent
      claudication. This study was aimed at evaluating its efficacy as an adjunct in
      the management of arterial ulceration. METHODS: The clinical records of patients
      treated with cilostazol from 2000 to 2010 at one institution were obtained. Of
      the 561 patients treated with cilostazol, we identified 82 (101 limbs) who
      started on therapy only after wounds were present and whose records were
      sufficient to assess healing. Only if all wounds in a limb completely healed
      without intervening arterial reconstruction, amputation, primary closure, or skin
      grafting, the limb was deemed healed with the assistance of cilostazol. With
      bilateral involvement, both limbs had to heal for the patient to be judged
      healed. Subjects who were lost to follow-up, died, or underwent surgical
      interventions other than debridement were deemed failures. Age, weight, height,
      body mass index (BMI), creatinine, diabetes, insulin therapy, hemodialysis,
      smoking history, congestive heart failure, cilostazol dose, and length of therapy
      were compared, as well as, the number of wounds, size of largest wound,
      chronicity, ankle-brachial index, the presence of exposed bone/tendon/joint, or
      the presence of gangrene. RESULTS: Overall 30 of 82 patients (36.6%) and 41 of
      101 (40.6%) limbs were deemed healed without surgical intervention or
      revascularization (open or endovascular). When 9 limbs that healed after skin
      grafts (n = 2) or foot-sparing amputations (n = 7) but without revascularization
      were considered, the overall rate of lower extremity limb salvage was 50.5%.
      Demographic characteristics were similar in the 2 groups except healed patients
      tended to be taller and weigh more but had similar BMI. The incidence of diabetes
      was higher in nonhealed limbs (73.3% vs. 50.0%, P = 0.0587). Gangrene was less
      common in healed patients (22.6% vs. 49.1%, P = 0.059) and healed limbs (22.0%
      vs. 48.3%, P = 0.027). Most subjects received 200 mg of cilostazol daily
      (healed:177 +/- 53 mg vs. nonhealed: 172 +/- 47 mg). Mean length of therapy in
      healed patients was 278 +/- 302 days compared with 108 +/- 129 days in nonhealed
      subjects before discontinuation of drug therapy or surgery, death, or loss to
      follow-up intervened. CONCLUSIONS: The observed limb healing rate with cilostazol
      compares favorably to the ~20% rate observed in subjects treated with placebo in
      multicenter trials of another vasodilator, iloprost. Although gangrene and
      diabetes correlate with lower prospects for healing, our data suggest that
      cilostazol helps promote healing of wounds when arterial insufficiency is
      present.

PMID- 24561210
TI  - Cavoatrial thrombectomy in hepatocellular carcinoma with tumor thrombus in the
      vena cava and atrium without the use of cardiopulmonary bypass.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) with tumor thrombus (TT) in hepatic
      vein, inferior vena cava (IVC), and right atrium (RA) portends a poor prognosis
      because of intravascular extension leading to rapid distal metastases. En bloc
      resection of cavoatrial TT without the use of cardiopulmonary bypass (CPB) is
      challenging. We describe a new method of vascular occlusion for thrombus entering
      into the RA without the need for CPB as shown in echocardiography. METHODS AND
      RESULTS: Retrospective analysis was carried out in 1 HCC patient, who had
      undergone hepatectomy with TT extension into IVC and RA. The infrahepatic IVC was
      occluded with vascular tape and the right atrial appendage was controlled with a
      Satinsky clamp proximal to the TT. The IVC wall was incised under direct vision
      from the infrahepatic IVC cranially. The tumor and thrombus were then removed en
      bloc under direct vision. Thus, cavoatrial thrombectomy was performed under total
      hepatic vascular exclusion without the use of CPB. He survived for 6 months and
      died of tumor recurrence. CONCLUSIONS: Using this technique, advanced HCC with
      cavoatrial TT can be resected safely without CPB and thereby avoid dislodgement
      of TT and air embolism.

PMID- 24561211
TI  - Endovascular treatment of bilateral common iliac artery aneurysms using
      bifurcated-unibody stent grafts.
AB  - BACKGROUND: Endovascular treatment of bilateral common iliac artery aneurysms
      (CIAA) is a promising alternative to open surgical repair. However, endovascular
      treatment is challenging when the CIAAs have short proximal necks and internal
      iliac artery needs to be preserved. METHODS/RESULTS: We report a case of a 62
      year-old man who presented with bilateral CIAA with short proximal necks, with
      the right-side aneurysm extended into the internal iliac artery. The aneurysms
      were successfully excluded by using a bifurcated-unibody stent graft on the left
      with preservation of its internal iliac artery; a conventional tubular covered
      stent was used on the right with occlusion of its internal iliac artery. In
      addition, an aorta-bi-iliac artery stent was used to provide extended proximal
      landing zones for the iliac stents. CONCLUSIONS: Endovascular repair using an
      iliac bifurcated-unibody stent graft can be a useful approach for the treatment
      of CIAAs. An aorta-bi-iliac endograft may also be needed to provide a reliable
      landing zone when the proximal neck of the iliac aneurysm is short.

PMID- 24561212
TI  - Endovascular management of a penetrating abdominal aortic injury.
AB  - Penetrating aortic trauma is associated with high mortality rates. We report the
      case of a 24-year-old man who presented with a self-inflicted abdominal aortic
      penetration injury, resulting in a pseudoaneurysm. Rather uniquely, he was
      managed through prophylactic stenting to his abdominal aorta; this case was also
      rare in that there were remarkably no associated visceral injuries. Stenting was
      preferred because of risks of an aortic graft in a young man. A 14-mm Atrium
      AdvantaTM stent was deployed, and angiography confirmed adequate exclusion of the
      pseudoaneurysm. He had no complications at follow-up. 

PMID- 24561213
TI  - A crowdful of letters: disentangling the role of similarity, eccentricity and
      spatial frequencies in letter crowding.
AB  - The present study investigated the joint impact of target-flanker similarity and
      of spatial frequency content on the crowding effect in letter identification. We
      presented spatial frequency filtered letters to neurologically intact non
      dyslexic readers while manipulating target-flanker distance, target eccentricity
      and target-flanker confusability (letter similarity metric based on published
      letter confusion matrices). The results show that high target-flanker
      confusability magnifies crowding. They also reveal an intricate pattern of
      interactions of the spatial frequency content of the stimuli with target
      eccentricity, flanker distance and similarity. The findings are congruent with
      the notion that crowding results from the inappropriate pooling of target and
      flanker features and that this integration is more likely to match a response
      template at a subsequent decision stage with similar than dissimilar flankers. In
      addition, the evidence suggests that crowding from similar flankers is biased
      towards relatively high spatial frequencies and that crowding shifts towards
      lower spatial frequencies as target eccentricity is increased. 

PMID- 24561214
TI  - Cytogenetically cryptic and FISH-negative PML/RARA rearrangement in acute
      promyelocytic leukemia detected only by PCR: an exceedingly rare phenomenon.

PMID- 24561216
TI  - Thermal signature of fear conditioning in mild post traumatic stress disorder.
AB  - Fear conditioning has been proposed as an important factor involved in the
      etiology of posttraumatic stress disorder (PTSD). We examined fear processing in
      PTSD patients with mild symptoms and in individuals who did not develop symptoms
      (both groups consisting of victims of a bank robbery), through the study of fear
      conditioned response. Conditioned responses were quantified by the skin
      conductance response (SCR) and the facial thermal response, the latter being
      measured by high-resolution functional thermal infrared (fIR) imaging. We found:
      (a) a change of the physiological parameters with respect to the baseline
      condition in both control subjects and PTSD patients during the conditioning
      phase; (b) the permanence of the conditioning effect in the maintenance phase in
      both control and PTSD patients; (c) patients and controls did differ for the
      variation across the phases of the physiological parameters rather than for their
      absolute values, showing that PTSD patients had a prolonged excitation and higher
      tonic component of autonomic activity. These results, although preliminary,
      indicate that the analysis of SCR and facial thermal response during the
      conditioning paradigm is a promising psychometric method of investigation, even
      in the case of low level of PTSD symptom severity. To the best of our knowledge,
      this study is the first attempt to discriminate between control subjects and PTSD
      patients with mild symptoms through infrared thermal imaging. It may suggest
      feasible approaches for diagnostic screening in the early phases of the disorder
      and in the assessment of preventive measures and therapies. 

PMID- 24561215
TI  - Association of interleukin-1beta -511 C/T polymorphism with tobacco-associated
      cancer in northeast India: a study on oral and gastric cancer.
AB  - The IL-1beta -511 C/T polymorphism is associated with increased IL-1 production
      and with increased risk of developing cancers. In this study, 251 patients (125
      with gastric cancer [GC] and 126 with oral cancer [OC]) and 207 normal controls
      from northeast (NE) India were genotyped for the IL-1beta -511 C/T polymorphism
      by PCR-restriction fragment length polymorphism (RFLP) and sequencing. Analysis
      of results showed betel-quid chewing to be a major risk factor (OR = 2.01, 95% CI
      = 1.05-3.87; P = 0.035) for OC. Inheritance of the IL-1beta -511 CT or TT
      resulted in a 2.6- to 3.05-fold increase in the risk of developing OC relative to
      that of participants who possessed the reference genotype (OR = 2.57, 95% CI =
      1.06-6.22; P = 0.036 and OR = 3.05, 95% CI = 1.22-7.63; P = 0.017), after
      adjusting for potential confounders. The dominant genetic model also confirmed
      the presence of the T allele as a significant risk factor for OC (OR = 2.72, 95%
      CI = 1.15-6.42; P = 0.02). In GC, interaction of the CT genotype with tobacco and
      betel-quid chewing habits conferred a significant 78% and 89% reduced risk of
      cancer, respectively. In conclusion, for the NE Indian population, the IL-1beta 
      511 CC and CT genotypes were significantly associated with increased risk of OC.
      However, the interaction of the CT genotype with risk habits may play a
      preventive role for GC but not for OC. 

PMID- 24561217
TI  - Brain sensorimotor system atrophy during the early stage of spinal cord injury in
      humans.
AB  - Spinal cord injury (SCI) usually leads to severe sensory and motor deficits below
      the spinal lesion. Previous animal models have shown significant atrophic changes
      in the neural sensorimotor system following SCI. However, specific anatomical
      changes in the human brain following SCI remain poorly understood. The purpose of
      the present study was to investigate structural changes during the early stage of
      SCI, and to investigate further the association between the structural changes
      and patients' sensorimotor functions. The study participants included 20 patients
      with SCI and 30 matched healthy controls. The mean period post-SCI was 8.9+/
      2.7weeks (range 4-12weeks). Voxel-based morphometry was used to investigate the
      regions with gray and white matter volume changes. Compared to healthy controls,
      patients with SCI showed significant gray matter atrophy in the primary motor
      cortex (M1), primary somatosensory cortex (S1), supplementary motor area (SMA),
      and thalamus, as well as white matter atrophy in the corticospinal tracts at the
      level of the bilateral cerebral peduncles. In addition, gray matter volume in the
      primary motor cortex was positively correlated with the total American Spinal
      Injury Association motor score in patients with SCI. In conclusion, our findings
      suggest that SCI causes significant anatomical changes in the human sensorimotor
      system, and that these anatomical changes may occur in the early phase of SCI.
      Future treatments that aim to restore sensorimotor functions following SCI need
      to attend to these anatomical changes in the brain. 

PMID- 24561218
TI  - Localization of alpha7 nicotinic acetylcholine receptor mRNA and protein within
      the cholinergic anti-inflammatory pathway.
AB  - Electrical stimulation of the vagus nerve attenuates tumor necrosis factor (TNF)
      synthesis by macrophages and reduces the systemic inflammatory response. Current
      evidence suggests that the alpha7 nicotinic acetylcholine receptor present in the
      celiac/superior mesenteric ganglia is a key component in vagus nerve signaling to
      the spleen; however, there is currently no direct anatomical evidence that the
      alpha7 receptor is present in the murine celiac/superior mesenteric ganglia. Our
      study addresses this deficiency by providing anatomical evidence that the alpha7
      receptor is expressed within the celiac/superior mesenteric ganglia and splenic
      nerve fibers using immunohistochemistry and quantitative polymerase chain
      reaction (qPCR). alpha7 receptor mRNA is highly expressed in the celiac/superior
      mesenteric ganglia and at low levels in the spleen compared to the brain. Double
      labeling for alpha7 and tyrosine hydroxylase shows that alpha7 receptor protein
      is present on noradrenergic neurons within the ganglia and prejunctionally on
      noradrenergic nerve fibers within the spleen. The alpha7 receptor in the ganglia
      provides a possible location for the action of alpha7-selective agonists, while
      prejunctional alpha7 receptor expressed on splenic nerves may induce an increase
      in norepinephrine release in a positive feedback system enhanced by lymphocyte
      derived acetylcholine. 

PMID- 24561219
TI  - Necroptosis inhibitor necrostatin-1 promotes cell protection and physiological
      function in traumatic spinal cord injury.
AB  - Spinal cord injury (SCI) is a common and serious trauma which lacks efficient
      treatment. Inhibition of cell death in the trauma area is important for spinal
      cord protection during this process. In this study, necroptosis inhibitor
      necrostatin-1 (Nec-1) was used to treat SCI rats, to investigate the role of Nec
      1 in the recovery of SCI. Nec-1 was found to reduce lesions, cytokines and
      reactive oxygen species (ROS), improve pathological conditions and blood supply
      in the spinal cord trauma area. Further study indicated that Nec-1 could inhibit
      necroptosis by inhibiting RIP1/3-MLKL recruitment and inhibit apoptosis by
      inhibiting Caspase 3 and Bax while activating Bcl-2. Ethological performance of
      SCI rats confirmed improvement and protection of physiological function by Nec-1.
      Nec-1 as a potential treatment for SCI warrants further study. To our knowledge,
      this is the first study on the role of Nec-1 in the treatment of traumatic SCI.
      Our research also found inhibition effects of Nec-1 on apoptosis, not only
      necroptosis - as reported by most publications. 

PMID- 24561220
TI  - Plant mitochondria: source and target for nitric oxide.
AB  - Plant mitochondria generate nitric oxide (NO) under anoxia through the action of
      cytochrome c oxidase and other electron transport chain components on nitrite.
      This reductive mechanism operates under aerobic conditions at high electron
      transport rates. Indirect evidence also indicates that the oxidative pathway of
      NO production may be associated with mitochondria. We review the consequences of
      mitochondrial NO production, including the inhibition of oxygen uptake by
      cytochrome c oxidase, the inhibition of aconitase and succinate dehydrogenase,
      the induction of alternative oxidase, and the nitrosylation of several proteins,
      including glycine decarboxylase. The importance of these events in adaptation to
      abiotic and biotic stresses is discussed. 

PMID- 24561221
TI  - MitoSatPlant: mitochondrial microsatellites database of viridiplantae.
AB  - Microsatellites also known as simple sequence repeats (SSRs) consist of 1-6
      nucleotide long repeating units. The importance of mitochondrial SSRs (mtSSRs) in
      fields like population genetics, plant phylogenetics and genome mapping motivated
      us to develop MitoSatPlant, a repository of plant mtSSRs. It contains information
      for perfect, imperfect and compound SSRs mined from 92 mitochondrial genomes of
      green plants, available at NCBI (as of 1 Feb 2014). A total of 72,798 SSRs were
      found, of which PCR primers were designed for 72,495 SSRs. Among all sequences,
      tetranucleotide repeats (26,802) were found to be most abundant whereas
      hexanucleotide repeats (2751) were detected with least frequency. MitoSatPlant
      was developed using SQL server 2008 and can be accessed through a front end
      designed in ASP.Net. It is an easy to use, user-friendly database and will prove
      to be a useful resource for plant scientists. To the best of our knowledge
      MitoSatPlant is the only database available for plant mtSSRs and can be freely
      accessed at http://compubio.in/mitosatplant/. 

PMID- 24561222
TI  - Aberrant CaMKII activity in the medial prefrontal cortex is associated with
      cognitive dysfunction in ADHD model rats.
AB  - Attention-deficit/hyperactivity disorder (ADHD) is a heterogeneous
      neurobehavioral disorder accompanied by cognitive and learning deficits, which is
      prevalent among boys. Juvenile male stroke-prone spontaneously hypertensive rats
      (SHRSP) exhibit ADHD-like behaviors including cognitive deficits and represent
      one animal model of ADHD. Here, we define a mechanism underlying cognitive
      dysfunction observed in SHRSP. Acute methylphenidate (MPH: 1mg/kg, p.o.)
      administration to SHRSP significantly improved not only inattention in a Y-maze
      task but also cognitive dysfunction in a novel object recognition test.
      Interestingly, Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) activity,
      which is essential for memory and learning acquisition, was excessively elevated
      in the medial prefrontal cortex (mPFC) but not in the hippocampal CA1 region of
      SHRSP compared with Wistar-Kyoto (WKY) rats. We also confirmed that elevated
      CaMKII autophosphorylation in the mPFC causes increased phosphorylation of the
      CaMKII substrate alpha-amino-3-hydroxy-5-methyl-4-isoxazolpropionic acid-type
      glutamate receptor subunit 1 (GluR1) (Ser-831). Ca(2+)-dependent phosphorylation
      levels of factors such as extracellular signal-regulated kinase (ERK) and protein
      kinase C (PKC) were unchanged in the SHRSP mPFC. Also, protein levels of the
      dopamine D2 receptor (D2R) but not the dopamine D1 receptor (D1R) were increased
      in the SHRSP mPFC. Acute MPH (1mg/kg, p.o.) administration attenuated aberrant
      CaMKII activity and increased GluR1 phosphorylation observed in SHRSP. Taken
      together, we propose that cognitive impairment in SHRSP is associated with
      aberrant CaMKII activity in the mPFC. 

PMID- 24561223
TI  - WHO guidance on the prevention of viral hepatitis B and C among people who inject
      drugs.
AB  - Viral hepatitis B and C (HBV, HCV) disproportionately affect people who inject
      drugs (PWID) across the world. To date there has been little global action
      focusing on prevention, care and treatment of HBV and HCV among PWID. Here we
      report on the development process and discuss the implications of evidence
      informed WHO Guidelines for the Prevention of HBV and HCV in PWID. The World
      Health Organization (WHO) convened a Guideline Development Panel to develop
      recommendations on the prevention of HBV and HCV among PWID. The process followed
      the Grading of Recommendations Assessment, Development and Evaluation (GRADE)
      methodology. It included the development of PICO (Population, Interventions,
      Comparator, Outcomes) questions and conducting systematic reviews. Quality of
      evidence was classified into 4 levels: high, moderate, low, and very low. In the
      process of moving from evidence to recommendations, the following were
      considered: quality of evidence, balance of benefits and harms, community values
      and preferences and resource use. The WHO recommendations include the following
      for working with PWID: offer the rapid HBV vaccination regimen; offer incentives
      to increase uptake and completion of the HBV vaccine schedule; needle and syringe
      programs should also provide low dead-space syringes for distribution; and offer
      peer interventions to reduce the incidence of viral hepatitis. This guideline
      complements other WHO documents regarding PWID, including HIV prevention
      initiatives such as needle and syringe programs and opioid substitution therapy.
      This guidance offers a first step in the prevention of HBV and HCV among PWID.
      However, the lack of high quality evidence in this area necessitates further
      research and resources for implementation. 

PMID- 24561224
TI  - Yolk contributes steroid to the multidimensional endocrine environment of embryos
      of Niveoscincus metallicus, a viviparous skink with a moderately complex
      placenta.
AB  - Maternally-derived testosterone (T) and 17-beta-oestradiol (E2) provide
      epigenetic mechanisms by which mothers can actively influence offspring
      phenotype. In amniotes, maternal steroids may be derived from yolk or transferred
      across the placenta according to parity mode. Viviparous reptiles utilise both a
      yolk and a placenta to support their developing embryos, but it has not yet been
      confirmed whether yolk is a source of maternal T and E2 in such species. We
      investigated this question using the viviparous lizard Niveoscincus metallicus as
      our model species. We measured T and E2 in the yolks during vitellogenesis,
      immediately post-ovulation and at progressive stages of gestation. Our results
      confirm that yolk is a substantial source of T and E2 in N. metallicus. Contrary
      to the pattern seen in many oviparous species, we did not observe a marked
      decline in yolk concentrations of either T or E2 after the initiation of sexual
      differentiation in the embryos. Rather, we found no statistically significant
      decline in yolk concentrations of both T and E2 post-ovulation. In viviparous
      reptiles that utilise both yolk and placenta to nourish their embryos, yolk
      likely plays an important role in these dynamics but that role is not yet clear.
      Further research is warranted to understand the importance of yolk steroids in
      the endocrine environment of the developing viviparous reptile. 

PMID- 24561225
TI  - Diversity of proton pumps in osteoclasts: V-ATPase with a3 and d2 isoforms is a
      major form in osteoclasts.
AB  - Osteoclasts acidify bone resorption lacunae through proton translocation by
      plasma membrane V-ATPase (vacuolar-type ATPase) which has an a3 isoform, one of
      the four isoforms of the trans-membrane a subunit (Toyomura et al., J. Biol.
      Chem., 278, 22023-22030, 2003). d2, a kidney- and epididymis-specific isoform of
      the d subunit, was also induced in osteoclast-like cells derived from the
      RAW264.7 line, and formed V-ATPase with a3. The amount of d2 in osteoclasts was 4
      fold higher than that of d1, a ubiquitous isoform. These results indicate that V
      ATPase with d2/a3 is a major osteoclast proton pump. Essentially the same results
      were obtained with osteoclasts derived from mouse spleen macrophages. Macrophages
      from a3-knock-out mice could differentiate into multi-nuclear cells with
      osteoclast-specific enzymes. In these cells, the d2 isoform was also induced and
      assembled in V-ATPase with the a1 or a2 isoform. However, they did not absorb
      calcium phosphate, indicating that V-ATPase with d2/a1 or d2/a2 could not perform
      the function of that with d2/a3. 

PMID- 24561226
TI  - Mitochondrial import and degradation of amyloid-beta peptide.
AB  - Mitochondrial dysfunctions associated with amyloid-beta peptide (Abeta)
      accumulation in mitochondria have been observed in Alzheimer's disease (AD)
      patients' brains and in AD mice models. Abeta is produced by sequential action of
      beta- and gamma-secretases cleaving the amyloid precursor protein (APP). The
      gamma-secretase complex was found in mitochondria-associated endoplasmic
      reticulum membranes (MAM) suggesting that this could be a potential site of Abeta
      production, from which Abeta is further transported into the mitochondria. In
      vitro, Abeta was shown to be imported into the mitochondria through the
      translocase of the outer membrane (TOM) complex. The mitochondrial presequence
      protease (PreP) is responsible for Abeta degradation reducing toxic effects of
      Abeta on mitochondrial functions. The proteolytic activity of PreP is, however,
      lower in AD brain temporal lobe mitochondria and in AD transgenic mice models,
      possibly due to an increased reactive oxygen species (ROS) production. Here, we
      review the intracellular mechanisms of Abeta production, its mitochondrial import
      and the intra-mitochondrial degradation. We also discuss the implications of a
      reduced efficiency of mitochondrial Abeta clearance for AD. Understanding the
      underlying mechanisms may provide new insights into mitochondria related
      pathogenesis of AD and development of drug therapy against AD. This article is
      part of a Special Issue entitled: 18th European Bioenergetic Conference. 

PMID- 24561227
TI  - Towards in vivo mutation analysis: knock-out of specific chlorophylls bound to
      the light-harvesting complexes of Arabidopsis thaliana - the case of CP24
      (Lhcb6).
AB  - In the last ten years, a large series of studies have targeted antenna complexes
      of plants (Lhc) with the aim of understanding the mechanisms of light harvesting
      and photoprotection. Combining spectroscopy, modeling and mutation analyses, the
      role of individual pigments in these processes has been highlighted in vitro. In
      plants, however, these proteins are associated with multiple complexes of the
      photosystems and function within this framework. In this work, we have envisaged
      a way to bridge the gap between in vitro and in vivo studies by knocking out in
      vivo pigments that have been proposed to play an important role in excitation
      energy transfer between the complexes or in photoprotection. We have complemented
      a CP24 knock-out mutant of Arabidopsis thaliana with the CP24 (Lhcb6) gene
      carrying a His-tag and with a mutated version lacking the ligand for chlorophyll
      612, a specific pigment that in vitro experiments have indicated as the lowest
      energy site of the complex. Both complexes efficiently integrated into the
      thylakoid membrane and assembled into the PSII supercomplexes, indicating that
      the His-tag does not impair the organization in vivo. The presence of the His-tag
      allowed the purification of CP24-WT and of CP24-612 mutant in their native
      states. It is shown that CP24-WT coordinates 10 chlorophylls and 2 carotenoid
      molecules and has properties identical to those of the reconstituted complex,
      demonstrating that the complex self-assembled in vitro assumes the same folding
      as in the plant. The absence of the ligand for chlorophyll 612 leads to the loss
      of one Chl a and of lutein, again as in vitro, indicating the feasibility of the
      method. This article is part of a special issue entitled: photosynthesis research
      for sustainability: keys to produce clean energy.

PMID- 24561229
TI  - Predictive risk factors for chronic regional and multisite musculoskeletal pain:
      a 5-year prospective study in a working population.
AB  - The role of psychosocial and physical factors in the development of
      musculoskeletal pain (MSP) has now been clearly demonstrated. However, it is
      unclear whether these factors contribute to specific regional MSP or to multisite
      pain. The main goal of this study was to assess the impact of work-related
      factors according to gender on the development of regional and multisite MSP. A
      total of 12,591 subjects (65% men and 35% women) who were born in 1938, 1943,
      1948, and 1953 and were participating in a French longitudinal prospective
      epidemiological survey (ESTEV) in 1990 to 1995 were eligible. Personal factors
      and work exposure were assessed by self-administered questionnaires. Statistical
      associations between chronic MSP (regional body site or multisite), personal
      factors, and occupational factors were analyzed using logistic regression
      modeling. The incidence of regional MSP and multisite pain in 1995 were,
      respectively, 17% and 25.6%. For women, highly repetitive movements predicted
      neck/shoulder pain; posture and vibrations predicted arm and low back pain; and
      effort with tools predicted arm pain. For men, forceful effort and vibrations
      predicted neck/shoulder pain; posture and forceful effort predicted lower limb
      and low back pain; and forceful effort and effort with tools predicted arm pain.
      Physical constraints (ie, forceful effort or vibrations) were associated with
      multisite pain in both genders. Only for women, psychological factors were risk
      factors predictive of upper limb pain and in 3 or 4 painful anatomical sites.
      These results support the hypothesis that some physical and psychological work
      related factors are predictive of regional or multisite MSP but differ according
      to gender. Gender differences and risk factors for work-related musculoskeletal
      pain should be also taken into account to more effectively target preventive
      measures. 

PMID- 24561228
TI  - Space, time, and causality in the human brain.
AB  - The ability to perceive causality is a central human ability constructed from
      elemental spatial and temporal information present in the environment. Although
      the nature of causality has captivated philosophers and scientists since
      antiquity, the neural correlates of causality remain poorly understood. In the
      present study, we used functional magnetic resonance imaging (fMRI) to generate
      hypotheses for candidate brain regions related to component processes important
      for perceptual causality in the human brain: elemental space perception,
      elemental time perception, and decision-making (Experiment 1; n=16). We then used
      transcranial direct current stimulation (tDCS) to test neural hypotheses
      generated from the fMRI experiment (Experiment 2; n=16). In both experiments,
      participants judged causality in billiard-ball style launching events; a blue
      ball approaches and contacts a red ball. Spatial and temporal contributions to
      causal perception were assessed by parametrically varying the spatial linearity
      and the temporal delays of the movement of the balls. Experiment 1 demonstrated
      unique patterns of activation correlated with spatial, temporal, and decision
      making components of causality perception. Using tDCS, we then tested hypotheses
      for the specific roles of the parietal and frontal cortices found in the fMRI
      experiment. Parietal stimulation only decreased participants' perception of
      causality based on spatial violations, while frontal stimulation made
      participants less likely to perceive causality based on violations of space and
      time. Converging results from fMRI and tDCS indicate that parietal cortices
      contribute to causal perception because of their specific role in processing
      spatial relations, while the frontal cortices contribute more generally,
      consistent with their role in decision-making. 

PMID- 24561230
TI  - Polymerases of hepatitis C viruses and flaviviruses: structural and mechanistic
      insights and drug development.
AB  - The family Flaviviridae comprises several major human pathogens including
      hepatitis C virus (genus hepacivirus), yellow fever virus, West Nile virus and
      dengue virus (genus flavivirus). Flaviviridae genomes comprise a single-stranded
      RNA segment encoding a single polyprotein that is subsequently processed into 10
      mature viral proteins. The nonstructural proteins are released from the C
      terminus of the polyprotein and contribute to the infectious cycle by forming
      membrane-bound, multi-protein compartments within host cells, named the
      replication complexes, where synthesis of new viral genomes takes place. Two
      nonstructural proteins are endowed with multiple enzymatic activities and
      represent important targets against which specific antiviral inhibitors have been
      developed. X-ray crystal structures of these viral enzymes as well as in-depth
      understanding of the molecular basis of their activities have contributed
      tremendously to the development of antiviral compounds, currently approved or in
      advanced clinical trials for hepatitis C treatment. One of the prime targets is
      the RNA-dependent RNA polymerase (RdRp, NS5B for hepatitis C virus, NS5 for
      flaviviruses). Here we review current knowledge of the structural basis for viral
      RNA synthesis by NS5B and NS5. These data offer perspectives for further drug
      design and constitute major advances in our basic understanding of viral RdRp.
      They thus point to future research directions in the field. 

PMID- 24561232
TI  - Health care-delivery research-training opportunities in gastroenterology and
      hepatology.

PMID- 24561233
TI  - Prediction in the service of comprehension: modulated early brain responses to
      omitted speech segments.
AB  - Speech signals are often compromised by disruptions originating from external
      (e.g., masking noise) or internal (e.g., inaccurate articulation) sources. Speech
      comprehension thus entails detecting and replacing missing information based on
      predictive and restorative neural mechanisms. The present study targets
      predictive mechanisms by investigating the influence of a speech segment's
      predictability on early, modality-specific electrophysiological responses to this
      segment's omission. Predictability was manipulated in simple physical terms in a
      single-word framework (Experiment 1) or in more complex semantic terms in a
      sentence framework (Experiment 2). In both experiments, final consonants of the
      German words Lachs ([laks], salmon) or Latz ([lats], bib) were occasionally
      omitted, resulting in the syllable La ([la], no semantic meaning), while brain
      responses were measured with multi-channel electroencephalography (EEG). In both
      experiments, the occasional presentation of the fragment La elicited a larger
      omission response when the final speech segment had been predictable. The
      omission response occurred ~125-165 msec after the expected onset of the final
      segment and showed characteristics of the omission mismatch negativity (MMN),
      with generators in auditory cortical areas. Suggestive of a general auditory
      predictive mechanism at work, this main observation was robust against varying
      source of predictive information or attentional allocation, differing between the
      two experiments. Source localization further suggested the omission response
      enhancement by predictability to emerge from left superior temporal gyrus and
      left angular gyrus in both experiments, with additional experiment-specific
      contributions. These results are consistent with the existence of predictive
      coding mechanisms in the central auditory system, and suggestive of the general
      predictive properties of the auditory system to support spoken word recognition. 

PMID- 24561234
TI  - An assessment of the impacts of the REDD+ pilot project on community forests user
      groups (CFUGs) and their community forests in Nepal.
AB  - REDD+ has the potential to reduce greenhouse gas emissions, meet climate
      stabilisation targets and protect biological diversity. Consequently, millions of
      dollars are being channelled into developing countries rich in forests, for pilot
      projects that will provide data for the design of REDD+ projects that are based
      on incentives and performance. This paper evaluates the impacts of REDD+ pilot
      projects on community forests and associated user groups (CFUGs) in Nepal. A
      field study targeted eight CFUGs that participated in a REDD+ pilot project
      funded by the Forest Carbon Trust Fund in Nepal. The pilot project increased the
      participation of Dalit, Indigenous people, women and the poor, and was able to
      provide some social safeguards. However, when all the additional costs and
      foregone benefits of the project are considered, REDD+ is not an attractive
      market-based option for Nepalese CFUGs. A better approach would be a bilateral or
      multilateral approach that is not market based, but provides incentives beyond
      environmental and social safeguards. The results of this study will be useful in
      designing REDD+ policies and programmes for community forest-based REDD+
      stakeholders in developing countries. 

PMID- 24561235
TI  - Applying a resting operation to alleviate bioclogging in vertical flow
      constructed wetlands: an experimental lab evaluation.
AB  - The aim of this study is to evaluate the effects of and analyze the reasons for
      applying a resting operation to alleviate bioclogging in vertical flow
      constructed wetlands (VFCWs). In parallel, three groups of laboratory-scale VFCWs
      were continuously fed with prepared wastewater (BOD = 600 mg/L) at a relatively
      high hydraulic loading rate of 0.5 m(3)/m(2).d until clogging. Parameters related
      to the clogging of the wetland substrate before and after resting were examined
      and measured. The results showed that the resting operation could effectively
      alleviate bioclogging because the hydraulic conductivity and effective porosity
      were improved after 3, 7 and 10 days of resting. In the upper 0-10 cm layer, the
      hydraulic conductivity increased 2.0, 2.6 and 3.5 times, respectively, for the
      three resting periods. The reduction of the extracellular polymeric substance
      (EPS), biofilm decay and the consequential change in the biofilm structure are
      the main reasons that the resting operation relieved clogging. In addition, the
      observed and theoretical resting times (approximately 7 days) agreed well. The
      results provide a theoretical basis and technical support for solving clogging
      problems. 

PMID- 24561231
TI  - Increased expression of EIF5A2, via hypoxia or gene amplification, contributes to
      metastasis and angiogenesis of esophageal squamous cell carcinoma.
AB  - BACKGROUND & AIMS: Solid tumors often become hypoxic, leading to activation of
      hypoxia-response genes. We investigated the effects of overexpression of the
      hypoxia response genes eIF5A2 in esophageal squamous cell carcinoma (ESCC).
      METHODS: We used quantitative real-time polymerase chain reaction and
      immunohistochemistry analyses to compare expression of eIF5A2 between paired ESCC
      samples and nontumor esophageal tissues, and fluorescence in situ hybridization
      to detect gene copy-number alterations. Luciferase reporter and chromatin
      immunoprecipitation assays were used to study interactions between eIF5A2 and
      hypoxia-inducible factor-1alpha (HIF1alpha). We determined the effects of eIF5A2
      overexpression and knockdown in ESCC cell lines and growth of ESCC xenograft
      tumors in nude mice. RESULTS: Levels of eIF5A2 messenger RNA and protein were
      increased in >40% of ESCC samples compared with matched nontumor tissues, along
      with levels of HIF1alpha and vascular endothelial growth factor. Increased levels
      of EIF5A2 were significantly associated with ESCC metastasis to lymph nodes (P <
      .001) and tissue invasion (P = .037), and shorter survival times of patients (P <
      .001). Amplification of eIF5A2 was detected in 35.14% of ESCC samples that
      overexpressed eIF5A2. Hypoxia increased expression of eIF5A2 4- to 8-fold in ESCC
      cell lines; we observed bidirectional regulation between eIF5A2 and HIF1alpha.
      Transient transfection of ESCC cell lines with eIF5A2 increased their migratory
      and invasive abilities and markers of the epithelial to mesenchymal transition,
      and eIF5A2 knockdown or HIFalpha inhibition reduced these. In mice, xenograft
      tumors grown from ESCC cells that expressed eIF5A2 formed tumors more rapidly
      than cells that expressed only vector (controls); they also expressed higher
      levels of HIF1alpha and vascular endothelial growth factor, and formed more
      microvessels than controls. Knockdown of eIF5A2 in ESCC cells with interfering
      RNAs reduced their growth as xenograft tumors in mice, particularly when mice
      were given docetaxel or cisplatin. CONCLUSIONS: eIF5A2 is overexpressed by gene
      amplification or hypoxia in ESCCs, and associated with up-regulation of
      HIF1alpha, metastasis, and shorter survival times of patients. Increased
      expression of eIF5A2 increases metastasis and angiogenesis in ESCC via the
      HIF1alpha-mediated signaling pathway.

PMID- 24561236
TI  - Is there an optimum scale for predicting bird species' distribution in
      agricultural landscapes?
AB  - Changes in forest cover in agricultural landscapes affect biodiversity. Its
      management needs some indications about scale to predict occurrence of
      populations and communities. In this study we considered a forest cover index to
      predict bird species and community patterns in agricultural landscapes in south
      western France. We used generalized linear models for that purpose with
      prediction driven by wooded areas' spatial distribution at nine different radii.
      Using 1064 point counts, we modelled the distribution of 10 bird species whose
      habitat preferences are spread along a landscape opening gradient. We also
      modelled the distribution of species richness for farmland species and for forest
      species. We used satellite images to construct a 'wood/non-wood' map and
      calculated a forest index, considering the surface area of wooded areas at nine
      radii from 110m to 910m. The models' predictive quality was determined by the AUC
      (for predicted presences) and rho (for predicted species richness) criteria. We
      found that the forest cover was a good predictor of the distribution of seven
      bird species in agricultural landscapes (mean AUC for the seven species = 0.74
      for the radius 110m). Species richness of farmland and forest birds was
      satisfactorily predicted by the models (rho = 0.55 and 0.49, respectively, for
      the radius 110m). The presence of the studied species and species richness
      metrics were better predicted at smaller scales (i.e. radii between 110 m and 310
      m) within the range tested. These results have implications for bird population
      management in agricultural landscapes since better pinpointing the scale to
      predict species distributions will enhance targeting efforts to be made in terms
      of landscape management. 

PMID- 24561237
TI  - The polymorphism of YWHAE, a gene encoding 14-3-3epsilon, and orbitofrontal
      sulcogyral pattern in patients with schizophrenia and healthy subjects.
AB  - An altered sulcogyral pattern in the orbitofrontal cortex (OFC) has been
      implicated in schizophrenia as a possible marker of abnormal neurodevelopment,
      while its genetic mechanism remains unknown. This magnetic resonance imaging
      study investigated the relationship between the polymorphism of YWHAE
      (rs28365859), a gene encoding 14-3-3epsilon that is a Disrupted-in-Schizophrenia
      1 (DISC1)-interacting molecule associated with neuronal development, and the OFC
      subtypes of the 'H-shaped' sulcus (Types I, II, and III) in a Japanese sample of
      72 schizophrenia patients and 86 healthy controls. The schizophrenia patients had
      significantly increased Type III (p = 0.004) and decreased Type I (p = 0.013)
      expression on the right hemisphere compared to the controls. The subjects
      carrying the protective C allele showed a decrease in Type III (p = 0.005) and an
      increase in Type I (p = 0.017) compared to the G allele homozygotes, especially
      for the healthy subjects in the left hemisphere. These results suggest a possible
      role for the YWHAE genotype in the early development of the OFC sulcogyral
      pattern, but its effect alone is not likely to explain the altered sulcogyral
      pattern in schizophrenia.

PMID- 24561239
TI  - Is there a pAkt between VEGF and oral cancer cell migration?
AB  - The PI3K-Akt signalling pathway is a well-established driver of cancer
      progression. One key process promoted by Akt phosphorylation is tumour cell
      motility; however the mechanism of VEGF-induced Akt phosphorylation leading to
      motility remains poorly understood. Previously, we have shown that Akt
      phosphorylation induced by different factors causes both stimulation and
      inhibition of motility in different cell types. However, differential
      phosphorylation of Akt at T308 and S473 residues by VEGF and its role in head and
      neck cancer cell motility and progression is unknown. The cell lines investigated
      in this study exhibited a change in phosphorylation of Akt in response to VEGF.
      However, in terms of motility, VEGF stimulated oral cancer and its associated
      cell lines, but not normal keratinocytes or oral mucosal fibroblasts. The
      addition of a PI3 kinase and mTOR inhibitor, inhibited the phosphorylation of Akt
      and also effectively blocked VEGF-induced oral cancer cell motility, whereas only
      the PI3 kinase inhibitor blocked oral cancer associated fibroblast cell motility.
      This study therefore discloses that two different mechanisms of Akt
      phosphorylation control the motility potential of different cell lines. Akt
      phosphorylated at both residues controls oral cancer cell motility. Furthermore,
      immunohistochemical analysis of VEGF positive human head and neck tumour tissues
      showed a significant increase in Akt phosphorylation at the T308 residue,
      suggesting that pAkt T308 may be associated with tumour progression in vivo. 

PMID- 24561240
TI  - Detoxification and decolorization of a simulated textile dye mixture by
      phytoremediation using Petunia grandiflora and, Gailardia grandiflora: a plant
      plant consortial strategy.
AB  - In vitro grown Petunia grandiflora and Gaillardia grandiflora plantlets showed 76
      percent and 62 percent American Dye Manufacturers Institute value (color) removal
      from a simulated dyes mixture within 36h respectively whereas their consortium
      gave 94 percent decolorization. P. grandiflora, G. grandiflora and their
      consortium could reduce BOD by 44 percent, 31 percent and, 69 percent and COD by
      58 percent, 37 percent and 73 percent respectively. Individually, root cells of
      P. grandiflora showed 74 and 24 percent induction in the activities of veratryl
      alcohol oxidase and laccase respectively; whereas G. grandiflora root cells
      showed 379 percent, 142 percent and 77 percent induction in the activities of
      tyrosinase, riboflavin reductase and lignin peroxidase respectively. In the
      consortium set, entirely a different enzymatic pattern was observed, where P.
      grandiflora root cells showed 231 percent, 12 percent and 65 percent induction in
      the activities of veratryl alcohol oxidase, laccase and 2, 6-dichlorophenol
      indophenol reductase respectively, while G. grandiflora root cells gave 300
      percent, 160 percent, 79 percent and 55 percent inductions in the activities of
      lignin peroxidase, riboflavin reductase, tyrosinase and laccase respectively.
      Because of the synergistic effect of the enzymes from both the plants, the
      consortium was found to be more effective for the degradation of dyes from the
      mixture. Preferential dye removal was confirmed by analyzing metabolites of
      treated dye mixture using UV-vis spectroscopy, FTIR and biotransformation was
      visualized using HPTLC. Metabolites formed after the degradation of dyes revealed
      the reduced cytogenotoxicity on Allium cepa roots cells when compared with
      untreated dye mixture solution. Phytotoxicity study exhibited the less toxic
      nature of the metabolites. 

PMID- 24561238
TI  - Phosphorylated SHIP2 on Y1135 localizes at focal adhesions and at the mitotic
      spindle in cancer cell lines.
AB  - The SH2 containing inositol 5-phosphatase SHIP2 is a member of the mammalian
      phosphoinositide polyphosphate 5-phosphatase family. It is a multi-domain protein
      comprising a central catalytic domain, an SH2 domain at its N-terminus, proline
      rich sequences and SAM domain at its C-terminus. It can dephosphorylate both
      phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P(3)) and phosphatidylinositol
      4,5-bisphosphate (PI(4,5)P(2)) and can participate in multiple signaling events
      in response to growth factors such as EGF, FGF or PDGF. Human SHIP2 can be
      phosphorylated at two major tyrosine residues Tyr986 and Tyr1135. Here, we report
      two intracellular localizations of pSHIP2(Y1135): pSHIP2(Y1135)-ir localizes at
      focal adhesions in EGF-stimulated HeLa cells and at the mitotic spindle in HeLa,
      in GIST882 cells, a human model of gastrointestinal stromal tumors derived cells,
      and in human astrocytoma 1321N1 cells. pSHIP2(Y1135)-ir is maximal at metaphase.
      In N1 cells, evidence is provided that the SHIP2 pathway impacts the distribution
      of mitotic centrosomes, particularly ?-tubulin. Our data reinforce the concept
      that SHIP2 localization in intact cells is dependent on phosphorylation
      mechanisms on both Ser/Thr and Tyr residues, i.e. Y1135, in three cancer cell
      lines.

PMID- 24561241
TI  - Effects of cadmium and lead on the life-cycle parameters of juvenile earthworm
      Eisenia fetida.
AB  - Juveniles Eisenia fetida were exposed to cadmium (1-500ugCdg(-1)) and lead (20
      2500ugPbg(-1)) for fourteen weeks in order to evaluate the impact on life-cycle
      parameters (survival, growth, sexual maturation, and cocoon production) and lipid
      peroxidation (expressed as concentration of malondialdehyde (MDA)). Both metals
      were found to significantly affect survival of the juveniles (fourteen-week LC50
      296+/-125ugCdg(-1) and 911+/-164ugPbg(-1)) and alter their development. Cd and Pb
      severely affected the weight of the juveniles, prolonged the time to sexual
      maturation (at the highest concentrations, earthworms did not reach sexual
      maturity at all), and reduced cocoon production. LC50 significantly decreased
      with the time of earthworm exposure, indicating that chronic exposure to the same
      levels of contaminants in the soil may have more detrimental consequences than
      short-term exposure. A survival model showed that the survival probability for
      the juveniles decreased significantly with time and the concentration of metals
      in the soil. The metals induced a significant increase in MDA concentration (2.98
      fold and 1.54-fold at 250ugCdg(-1) and 2500ugPbg(-1), respectively), and the
      content of MDA was negatively related to the weight of the juveniles and the
      percentage of mature individuals (p<0.05). 

PMID- 24561243
TI  - Behaviour of the oxidant scavenger metallothionein in hypoxia-induced neotropical
      fish.
AB  - The pacu (Piaractus mesopotamicus) is a hypoxia-tolerant neotropical fish
      species. There is little or no information in this species regarding biochemical
      adaptations to waters with different oxygen concentrations, such as the
      production of reactive oxygen species and antioxidant scavengers, which might be
      of interest in the study of antioxidant defense mechanisms. Metallothioneins (MT)
      have been widely applied as biomarkers for metal exposure in fish liver, and,
      recently, in bile. These metalloproteins, however, have also been reported as
      free radical scavengers, although studies in this regard are scarce in fish. In
      this context, normoxic and hypoxic controlled experiments were conducted with
      pacu specimens and MT levels were quantified in both liver and bile. Reduced
      glutathione (GSH) indicative of oxidative stress, and thiobarbituric acid
      reactive substances (TBARS), indicative of lipid peroxidation, were also
      determined in liver. The results demonstrate that hypoxic fish present
      significantly lower metallothionein levels in liver and bile and lower reduced
      glutathione levels in liver, whereas lipid peroxidation was not significantly
      different between hypoxic and normoxic fish. The results of the present study
      seem to suggest that metallothioneins may actively participate in redox
      regulation in hypoxic fish in both bile and liver. MT levels in these organs may
      be temporarily suppressed, supporting the notion that down-regulation of oxidant
      scavengers during the oxidative burst is important in defense signaling in these
      adapted organisms. 

PMID- 24561242
TI  - Assessment of domestic landfill leachate toxicity to the Asian clam Corbicula
      fluminea via biomarkers.
AB  - In order to evaluate the effects of domestic landfill leachate to bivalves
      Corbicula fluminea, clams were exposed to different leachate concentrations
      (v/v): 2, 3, 6 and 10 percent, corresponding to dilutions observed along a stream
      that receives this effluent, or only to clean water for comparisons. After 5 and
      15 days of exposure the activity of the biotransformation enzymes 7
      ethoxyresorufin-O-deethylase (EROD) and glutathione S-transferase (GST), the
      multixenobiotic resistance mechanism (MXR) and lipid peroxidation (LPO) in gills
      and digestive gland and metallothionein (MT) content in gills were evaluated.
      Differences in biomarkers responses were observed between gills and digestive
      gland, except for MXR that decreased in both tissues of clams exposed to 6
      percent for 5 days. EROD activity in gills was reduced in all leachate
      concentrations after 5 days and only in 2 percent after 15 days exposure, while
      an EROD increase was observed in digestive gland after 15 days exposure to 6
      percent. GST activity increased only in the gills of clams exposed to 10 percent
      for 5 days. LPO varied between tissues and different conditions. A significant
      increase in LPO was observed in the gills, after 5 days exposure to 2 and 6
      percent, and in digestive gland after 5 and 15 days exposure to 2 and 3 percent.
      MT content in the gills increased after 15 days exposure to 2 percent. In
      conclusion, different leachate concentrations tested here caused biochemical
      changes in C. fluminea, but due to the observed variability in biomarkers
      responses among leachate concentrations, it was difficult to determine patterns
      or thresholds concentrations. 

PMID- 24561244
TI  - E3-ligase Skp2 regulates beta-catenin expression and maintains hematopoietic stem
      cell homing.
AB  - The homing ability of hematopoietic stem cells (HSCs) was a critical step for
      transplantation and subsequent hematopoiesis. Although the HSC transplantation
      was widely used for many diseases, the mechanism by which HSC homing was
      regulated remained poorly understood. F-box protein S-phase kinase associated
      protein2 (Skp2), a component of the Skp2-SCF E3 ligase complex, was regarded as a
      cell cycle regulator by controlling the level of p21 and p27 through
      ubiquitination. We recently reported an important role of Skp2 in maintaining HSC
      pool size, quiescent stage and self-renewal ability. In this current study, we
      showed that Skp2 was a novel and critical regulator for maintaining the homing of
      HSCs as well as their residence in the endosteal niche. Microarray analysis
      together with biochemical validations revealed that Skp2 deficiency profoundly
      reduced the expression of beta-catenin and its target genes. Knockdown of beta
      catenin mimicked the decline of HSC homing upon Skp2 deficiency, suggesting that
      Skp2 may regulate beta-catenin and its target gene expression to orchestrate HSC
      homing. Our study not only identified Skp2 as a new regulator for maintaining
      beta-catenin expression and HSC homing, but also suggested that Skp2 may serve as
      a predictive marker for monitoring the transplantation efficiency. 

PMID- 24561245
TI  - A high-throughput assay of NK cell activity in whole blood and its clinical
      application.
AB  - Natural killer (NK) cells are lymphocytes of the innate immune system and have
      the ability to kill tumor cells and virus-infected cells without prior
      sensitization. Malignant tumors and viruses have developed, however, strategies
      to suppress NK cells to escape from their responses. Thus, the evaluation of NK
      cell activity (NKA) could be invaluable to estimate the status and the outcome of
      cancers, viral infections, and immune-mediated diseases. Established methods that
      measure NKA, such as (51)Cr release assay and CD107a degranulation assay, may be
      used to determine NK cell function, but they are complicated and time-consuming
      because they require isolation of peripheral blood mononuclear cells (PBMC) or NK
      cells. In some cases these assays require hazardous material such as radioactive
      isotopes. To overcome these difficulties, we developed a simple assay that uses
      whole blood instead of PBMC or isolated NK cells. This novel assay is suitable
      for high-throughput screening and the monitoring of diseases, because it employs
      serum of ex vivo stimulated whole blood to detect interferon (IFN)-gamma secreted
      from NK cells as an indicator of NKA. After the stimulation of NK cells, the
      determination of IFNgamma concentration in serum samples by enzyme-linked
      immunosorbent assay (ELISA) provided a swift, uncomplicated, and high-throughput
      assay of NKA ex vivo. The NKA results microsatellite stable (MSS) colorectal
      cancer patients was showed significantly lower NKA, 263.6 +/- 54.5 pg/mL compared
      with healthy subjects, 867.5 +/- 50.2 pg/mL (p value <0.0001). Therefore, the NKA
      could be utilized as a supportive diagnostic marker for microsatellite stable
      (MSS) colorectal cancer.

PMID- 24561246
TI  - Fertility sparing treatment of complex atypical hyperplasia and low grade
      endometrial cancer using oral progestin.
AB  - OBJECTIVE: Oral progestin is an alternative to hysterectomy for women with
      complex atypical hyperplasia (CAH) or grade one endometrial cancer (G1EC) who
      wish fertility preservation. We evaluated treatment efficacy and fertility
      outcomes in this population. METHODS: Women <45 y treated with oral progestin for
      CAH or G1EC were identified from two cancer centers. Data were obtained from
      medical records and telephone questionnaires. Time until complete response (CR),
      and from CR until recurrence was censored for patients without events and
      analyzed for associations with patient and treatment characteristics; cumulative
      incidence functions were used to estimate event probability over time. RESULTS:
      44 patients were identified, 19 (43%) with CAH and 25 (57%) with G1EC. Median age
      was 36.5 y (26-44). 24 (55%) achieved CR (median time: 5.7 months). Older age was
      associated with a lower likelihood of CR (HR 0.84, p=0.0003, 95% CI, 0.8-0.9). CR
      probability appeared to plateau after 12 months of therapy. Among those with CR,
      13 (54%) recurred (median time 3.5 y). 24 patients (55%) underwent hysterectomy;
      3 (13%) were upstaged. 11 (25%) underwent fertility treatment with the following
      outcomes: 6 (55%) no pregnancy, 2 (18%) at least one live infant, and 3 (27%)
      spontaneous abortion. One achieved a live birth without intervention. CONCLUSION:
      Oral progestin is an effective temporizing fertility-sparing treatment for women
      with CAH/G1EC. Fertility specialist involvement is recommended due to the low
      live birth rate without intervention. Progestin therapy should be re-evaluated at
      1 year in non-responders due to a low probability of success. Hysterectomy is
      recommended after childbearing due to a high recurrence rate.

PMID- 24561248
TI  - Arabidopsis thaliana mutant lpsi reveals impairment in the root responses to
      local phosphate availability.
AB  - Phosphate (Pi) deficiency triggers local Pi sensing-mediated inhibition of
      primary root growth and development of root hairs in Arabidopsis (Arabidopsis
      thaliana). Generation of activation-tagged T-DNA insertion pools of Arabidopsis
      expressing the luciferase gene (LUC) under high-affinity Pi transporter (Pht1;4)
      promoter, is an efficient approach for inducing genetic variations that are
      amenable for visual screening of aberrations in Pi deficiency responses. Putative
      mutants showing altered LUC expression during Pi deficiency were identified and
      screened for impairment in local Pi deficiency-mediated inhibition of primary
      root growth. An isolated mutant was analyzed for growth response, effects of Pi
      deprivation on Pi content, primary root growth, root hair development, and
      relative expression levels of Pi starvation-responsive (PSR) genes, and those
      implicated in starch metabolism and Fe and Zn homeostasis. Pi deprived local
      phosphate sensing impaired (lpsi) mutant showed impaired primary root growth and
      attenuated root hair development. Although relative expression levels of PSR
      genes were comparable, there were significant increases in relative expression
      levels of IRT1, BAM3 and BAM5 in Pi deprived roots of lpsi compared to those of
      the wild-type. Better understanding of molecular responses of plants to Pi
      deficiency or excess will help to develop suitable remediation strategies for
      soils with excess Pi, which has become an environmental concern. Hence, lpsi
      mutant will serve as a valuable tool in identifying molecular mechanisms
      governing adaptation of plants to Pi deficiency. 

PMID- 24561247
TI  - Patterns of care, predictors, and outcomes of chemotherapy in elderly women with
      early-stage uterine carcinosarcoma: a population-based analysis.
AB  - OBJECTIVE: To examine the patterns of care, predictors, and impact of
      chemotherapy on survival in elderly women diagnosed with early-stage uterine
      carcinosarcoma. METHODS: The Surveillance, Epidemiology, and End Results (SEER)
      Medicare database was used to identify women 65 years or older diagnosed with
      stage I-II uterine carcinosarcomas from 1991 through 2007. Multivariable logistic
      regression and Cox-proportional hazards models were used for statistical
      analysis. RESULTS: A total of 462 women met the eligibility criteria; 374 had
      stage I, and 88 had stage II uterine carcinosarcomas. There were no appreciable
      differences over time in the percentages of women administered chemotherapy for
      early stage uterine carcinosarcoma (14.7% in 1991-1995, 14.9% in 1996-2000, and
      17.9% in 2001-2007, P=0.67). On multivariable analysis, the factors positively
      associated with receipt of chemotherapy were younger age at diagnosis, higher
      disease stage, residence in the eastern part of the United States, and lack of
      administration of external beam radiation (P<0.05). In the adjusted Cox
      proportional hazards regression models, administration of three or more cycles of
      chemotherapy did not reduce the risk of death in stage I patients (HR: 1.45, 95%
      CI: 0.83-2.39) but was associated with non-significant decreased mortality in
      stage II patients (HR: 0.83, 95% CI: 0.32-1.95). CONCLUSIONS: Approximately 15
      18% of elderly patients diagnosed with early-stage uterine carcinosarcoma were
      treated with chemotherapy. This trend remained stable over time, and chemotherapy
      was not associated with any significant survival benefit in this patient
      population.

PMID- 24561249
TI  - AtWNK9 is regulated by ABA and dehydration and is involved in drought tolerance
      in Arabidopsis.
AB  - WNK (with no lysine [K]) kinases play important regulatory roles in flowering, as
      well as salt and osmotic stress tolerance in plants. Here, we report that AtWNK9,
      a member of the Arabidopsis WNK gene family, was induced by exogenous abscisic
      acid (ABA) treatment and dehydration stress. Overexpression of AtWNK9 from the
      cauliflower mosaic virus 35S promoter in Arabidopsis resulted in increased
      sensitivity to ABA, strong inhibition of primary root elongation, increased
      proline accumulation, reduced stomatal aperture, and a reduced rate of water
      loss. In addition, plant survival under drought stress was improved compared to
      wild type. In contrast, a mutant with a T-DNA insertion in AtWNK9 showed reduced
      ABA sensitivity and an increased rate of water loss; further, it showed increased
      susceptibility to drought stress. The transcription of a number of ABA signaling
      components, including ABI1, ERA1, ABI3, and ABF3, was up-regulated in AtWNK9
      transgenic plants and down-regulated in the wnk9 mutant in response to ABA. Some
      ABA-responsive and biosynthetic genes, as well as other drought-related genes,
      were altered at various levels in AtWNK9 transgenic plants and wnk9 mutants under
      dehydration stress. Overall, these findings suggest that AtWNK9 plays a positive
      role in ABA signaling and improves drought tolerance in transgenic Arabidopsis. 

PMID- 24561251
TI  - Telomerase activation: a potential key modulator for human healthspan and
      longevity.
AB  - The elderly population is increasing progressively. Along with this increase the
      number of age related diseases, such as cardiovascular, neurodegenerative
      diseases, metabolic impairment and cancer, is also on the rise thereby negatively
      impacting the burden on health care systems. Telomere shortening and dysfunction
      results in cellular senescence, an irreversible proliferative arrest that has
      been suggested to promote organismal aging and disabling age-related diseases.
      Given that telomerase, the enzyme responsible for maintaining telomere lengths,
      is not expressed at levels sufficient to prevent telomere shortening in most of
      our cells, telomeres progressively erode with advancing age. Telomerase
      activation, therefore, might serve as a viable therapeutic strategy to delay the
      onset of cellular senescence, tissue dysfunction and organismal decline. Here we
      analyze the more recent findings in telomerase activation as a potential key
      modulator for human healthspan and longevity. 

PMID- 24561252
TI  - RNA-DNA differences are generated in human cells within seconds after RNA exits
      polymerase II.
AB  - RNA sequences are expected to be identical to their corresponding DNA sequences.
      Here, we found all 12 types of RNA-DNA sequence differences (RDDs) in nascent
      RNA. Our results show that RDDs begin to occur in RNA chains ~55 nt from the RNA
      polymerase II (Pol II) active site. These RDDs occur so soon after transcription
      that they are incompatible with known deaminase-mediated RNA-editing mechanisms.
      Moreover, the 55 nt delay in appearance indicates that they do not arise during
      RNA synthesis by Pol II or as a direct consequence of modified base
      incorporation. Preliminary data suggest that RDD and R-loop formations may be
      coupled. These findings identify sequence substitution as an early step in
      cotranscriptional RNA processing.

PMID- 24561253
TI  - Small molecules enable cardiac reprogramming of mouse fibroblasts with a single
      factor, Oct4.
AB  - It was recently shown that mouse fibroblasts could be reprogrammed into cells of
      a cardiac fate by forced expression of multiple transcription factors and
      microRNAs. For ultimate application of such a reprogramming strategy for cell
      based therapy or in vivo cardiac regeneration, reducing or eliminating the
      genetic manipulations by small molecules would be highly desirable. Here, we
      report the identification of a defined small-molecule cocktail that enables the
      highly efficient conversion of mouse fibroblasts into cardiac cells with only one
      transcription factor, Oct4, without any evidence of entrance into the pluripotent
      state. Small-molecule-induced cardiomyocytes spontaneously contract and exhibit a
      ventricular phenotype. Furthermore, these induced cardiomyocytes pass through a
      cardiac progenitor stage. This study lays the foundation for future
      pharmacological reprogramming approaches and provides a small-molecule condition
      for investigation of the mechanisms underlying the cardiac reprogramming process.

PMID- 24561250
TI  - The role of inflammasome in Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a chronic, progressive and irreversible
      neurodegenerative disease with clinical characteristics of memory loss, dementia
      and cognitive impairment. Although the pathophysiologic mechanism is not fully
      understood, inflammation has been shown to play a critical role in the
      pathogenesis of AD. Inflammation in the central nervous system (CNS) is
      characterized by the activation of glial cells and release of proinflammatory
      cytokines and chemokines. Accumulating evidence demonstrates that inflammasomes,
      which cleave precursors of interleukin-1beta (IL-1beta) and IL-18 to generate
      their active forms, play an important role in the inflammatory response in the
      CNS and in AD pathogenesis. Therefore, modulating inflammasome complex assembly
      and activation could be a potential strategy for suppressing inflammation in the
      CNS. This review aims to provide insight into the role of inflammasomes in the
      CNS, with respect to the pathogenesis of AD, and may provide possible clues for
      devising novel therapeutic strategies. 

PMID- 24561254
TI  - PTEN C-terminal deletion causes genomic instability and tumor development.
AB  - Tumor suppressor PTEN controls genomic stability and inhibits tumorigenesis. The
      N-terminal phosphatase domain of PTEN antagonizes the PI3K/AKT pathway, but its C
      terminal function is less defined. Here, we describe a knockin mouse model of a
      nonsense mutation that results in the deletion of the entire Pten C-terminal
      region, referred to as Pten(DeltaC). Mice heterozygous for Pten(DeltaC) develop
      multiple spontaneous tumors, including cancers and B cell lymphoma. Heterozygous
      deletion of the Pten C-terminal domain also causes genomic instability and common
      fragile site rearrangement. We found that Pten C-terminal disruption induces p53
      and its downstream targets. Simultaneous depletion of p53 promotes metastasis
      without influencing the initiation of tumors, suggesting that p53 mainly
      suppresses tumor progression. Our data highlight the essential role of the PTEN C
      terminus in the maintenance of genomic stability and suppression of
      tumorigenesis. 

PMID- 24561255
TI  - RTEL1 inhibits trinucleotide repeat expansions and fragility.
AB  - Human RTEL1 is an essential, multifunctional helicase that maintains telomeres,
      regulates homologous recombination, and helps prevent bone marrow failure. Here,
      we show that RTEL1 also blocks trinucleotide repeat expansions, the causal
      mutation for 17 neurological diseases. Increased expansion frequencies of
      (CTG?CAG) repeats occurred in human cells following knockdown of RTEL1, but not
      the alternative helicase Fbh1, and purified RTEL1 efficiently unwound triplet
      repeat hairpins in vitro. The expansion-blocking activity of RTEL1 also required
      Rad18 and HLTF, homologs of yeast Rad18 and Rad5. These findings are reminiscent
      of budding yeast Srs2, which inhibits expansions, unwinds hairpins, and prevents
      triplet-repeat-induced chromosome fragility. Accordingly, we found expansions and
      fragility were suppressed in yeast srs2 mutants expressing RTEL1, but not Fbh1.
      We propose that RTEL1 serves as a human analog of Srs2 to inhibit (CTG?CAG)
      repeat expansions and fragility, likely by unwinding problematic hairpins.

PMID- 24561257
TI  - Endothelial cilia mediate low flow sensing during zebrafish vascular development.
AB  - VIDEO ABSTRACT: The pattern of blood flow has long been thought to play a
      significant role in vascular morphogenesis, yet the flow-sensing mechanism that
      is involved at early embryonic stages, when flow forces are low, remains unclear.
      It has been proposed that endothelial cells use primary cilia to sense flow, but
      this has never been tested in vivo. Here we show, by noninvasive, high-resolution
      imaging of live zebrafish embryos, that endothelial cilia progressively deflect
      at the onset of blood flow and that the deflection angle correlates with calcium
      levels in endothelial cells. We demonstrate that alterations in shear stress,
      ciliogenesis, or expression of the calcium channel PKD2 impair the endothelial
      calcium level and both increase and perturb vascular morphogenesis. Altogether,
      these results demonstrate that endothelial cilia constitute a highly sensitive
      structure that permits the detection of low shear forces during vascular
      morphogenesis.

PMID- 24561256
TI  - Laminar and temporal expression dynamics of coding and noncoding RNAs in the
      mouse neocortex.
AB  - The hallmark of the cerebral neocortex is its organization into six layers, each
      containing a characteristic set of cell types and synaptic connections. The
      transcriptional events involved in laminar development and function still remain
      elusive. Here, we employed deep sequencing of mRNA and small RNA species to gain
      insights into transcriptional differences among layers and their temporal
      dynamics during postnatal development of the mouse primary somatosensory
      neocortex. We identify a number of coding and noncoding transcripts with specific
      spatiotemporal expression and splicing patterns. We also identify signature
      trajectories and gene coexpression networks associated with distinct biological
      processes and transcriptional overlap between these processes. Finally, we
      provide data that allow the study of potential miRNA and mRNA interactions.
      Overall, this study provides an integrated view of the laminar and temporal
      expression dynamics of coding and noncoding transcripts in the mouse neocortex
      and a resource for studies of neurodevelopment and transcriptome.

PMID- 24561259
TI  - Are long chain acyl CoAs responsible for suppression of mitochondrial metabolism
      in hibernating 13-lined ground squirrels?
AB  - Hibernation in 13-lined ground squirrels (Ictidomys tridecemlineatus) is
      associated with a substantial suppression of whole-animal metabolism. We compared
      the metabolism of liver mitochondria isolated from torpid ground squirrels with
      those from interbout euthermic (IBE; recently aroused from torpor) and summer
      euthermic conspecifics. Succinate-fuelled state 3 respiration, calculated
      relative to mitochondrial protein, was suppressed in torpor by 48% and 44%
      compared with IBE and summer, respectively. This suppression remains when
      respiration is expressed relative to cytochrome c oxidase activity. We
      hypothesized that this suppression was caused by inhibition of succinate
      transport at the dicarboxylate transporter (DCT) by long-chain fatty acyl CoAs
      that may accumulate during torpor. We predicted, therefore, that exogenous
      palmitoyl CoA would inhibit respiration in IBE more than in torpor. Palmitoyl CoA
      inhibited respiration ~70%, in both torpor and IBE. The addition of carnitine,
      predicted to reverse palmitoyl CoA suppression by facilitating its transport into
      the mitochondrial matrix, did not rescue the respiration rates in IBE or torpor.
      Liver mitochondrial activities of carnitine palmitoyl transferase did not differ
      among IBE, torpor and summer animals. Although palmitoyl CoA inhibits succinate
      fuelled respiration, this suppression is likely not related exclusively to
      inhibition of the DCT, and may involve additional mitochondrial transporters such
      as the adenine-nucleotide transporter. 

PMID- 24561258
TI  - Breaking bonds in male prairie vole: long-term effects on emotional and social
      behavior, physiology, and neurochemistry.
AB  - Social relationships are essential for many fundamental aspects of life while
      bond disruption can be detrimental to mental and physical health. Male prairie
      voles form enduring social bonds with their female partners, allowing the
      evaluation of partner loss on behavior, physiology, and neurochemistry. Males
      were evaluated for partner preference formation induced by 24h of mating, and
      half were separated from their partner for 4 wk. In Experiment 1, partner loss
      significantly increased anxiety-like behaviors in the elevated plus maze and
      light-dark box tests and marginally increased depressive-like behaviors in the
      forced swim test. In addition, while intruder-directed aggression is common in
      pair bonded prairie voles, separated males were affiliative and lacked aggression
      toward an unfamiliar female and an intruding male conspecific. Partner loss
      increased the density of oxytocin-immunoreactivity (-ir), vasopressin-ir, and
      corticotrophin-releasing hormone-ir cells in the paraventricular nucleus of the
      hypothalamus and oxytocin-ir cells in the supraoptic nucleus. Tyrosine
      hydroxylase-ir was not affected. In Experiment 2, partner preference was observed
      after 2 wk of partner loss but eliminated after 4 wk partner loss. Body weight
      gain and plasma corticosterone concentrations were elevated throughout the 4 wk.
      No effects were observed for plasma oxytocin or vasopressin. Together, partner
      loss elicits anxiety-like and depression-like behaviors, disrupts bond-related
      behaviors, and alters neuropeptide systems that regulate such behaviors. Thus,
      partner loss in male prairie voles may provide a model to better understand the
      behavior, pathology, and neurobiology underlying partner loss and grief.

PMID- 24561260
TI  - Mitohormesis.
AB  - For many years, mitochondria were viewed as semiautonomous organelles, required
      only for cellular energetics. This view has been largely supplanted by the
      concept that mitochondria are fully integrated into the cell and that
      mitochondrial stresses rapidly activate cytosolic signaling pathways that
      ultimately alter nuclear gene expression. Remarkably, this coordinated response
      to mild mitochondrial stress appears to leave the cell less susceptible to
      subsequent perturbations. This response, termed mitohormesis, is being rapidly
      dissected in many model organisms. A fuller understanding of mitohormesis
      promises to provide insight into our susceptibility for disease and potentially
      provide a unifying hypothesis for why we age. 

PMID- 24561263
TI  - The protein import machinery of mitochondria-a regulatory hub in metabolism,
      stress, and disease.
AB  - Mitochondria fulfill central functions in bioenergetics, metabolism, and
      apoptosis. They import more than 1,000 different proteins from the cytosol. It
      had been assumed that the protein import machinery is constitutively active and
      not subject to detailed regulation. However, recent studies indicate that
      mitochondrial protein import is regulated at multiple levels connected to
      cellular metabolism, signaling, stress, and pathogenesis of diseases. Here, we
      discuss the molecular mechanisms of import regulation and their implications for
      mitochondrial homeostasis. The protein import activity can function as a sensor
      of mitochondrial fitness and provides a direct means of regulating biogenesis,
      composition, and turnover of the organelle.

PMID- 24561261
TI  - Islet microenvironment, modulated by vascular endothelial growth factor-A
      signaling, promotes beta cell regeneration.
AB  - Pancreatic islet endocrine cell and endothelial cell (EC) interactions mediated
      by vascular endothelial growth factor-A (VEGF-A) signaling are important for
      islet differentiation and the formation of highly vascularized islets. To dissect
      how VEGF-A signaling modulates intra-islet vasculature, islet microenvironment,
      and beta cell mass, we transiently increased VEGF-A production by beta cells.
      VEGF-A induction dramatically increased the number of intra-islet ECs but led to
      beta cell loss. After withdrawal of the VEGF-A stimulus, beta cell mass,
      function, and islet structure normalized as a result of a robust, but transient,
      burst in proliferation of pre-existing beta cells. Bone marrow-derived
      macrophages (MPhis) recruited to the site of beta cell injury were crucial for
      the beta cell proliferation, which was independent of pancreatic location and
      circulating factors such as glucose. Identification of the signals responsible
      for the proliferation of adult, terminally differentiated beta cells will improve
      strategies aimed at beta cell regeneration and expansion.

PMID- 24561262
TI  - Supercompetitor status of Drosophila Myc cells requires p53 as a fitness sensor
      to reprogram metabolism and promote viability.
AB  - In growing tissues, cell fitness disparities can provoke interactions that
      promote stronger cells at the expense of the weaker in a process called cell
      competition. The mechanistic definition of cell fitness is not understood, nor is
      it understood how fitness differences are recognized. Drosophila cells with extra
      Myc activity acquire "supercompetitor" status upon confrontation with wild-type
      (WT) cells, prompting the latter's elimination via apoptosis. Here we show that
      such confrontation enhances glycolytic flux in Myc cells and promotes their
      fitness and proliferation in a p53-dependent manner. Whereas p53 loss in
      noncompeting Myc cells is inconsequential, its loss impairs metabolism, reduces
      viability, and prevents the killing activity of Myc supercompetitor cells. We
      propose that p53 acts as a general sensor of competitive confrontation to enhance
      the fitness of the "winner" population. Our findings suggest that the initial
      confrontation between precancerous and WT cells could enhance cancer cell fitness
      and promote tumor progression.

PMID- 24561264
TI  - Development and bioanalytical validation of a liquid chromatographic-tandem mass
      spectrometric (LC-MS/MS) method for the quantification of the CCR5 antagonist
      maraviroc in human plasma.
AB  - BACKGROUND: Maraviroc is a CCR5 antagonist that has been utilized as a viral
      entry inhibitor in the management of HIV-1. Current clinical trials are pursuing
      maraviroc drug efficacy in both oral and topical formulations. Therefore, in
      order to fully understand drug pharmacokinetics, a sensitive method is required
      to quantify plasma drug concentrations. METHODS: Maraviroc-spiked plasma was
      combined with acetonitrile containing an isotopically-labeled internal standard,
      and following protein precipitation, samples were evaporated to dryness and
      reconstituted for liquid chromatographic-tandem mass spectrometric (LC-MS/MS)
      analysis. Chromatographic separation was achieved on a Waters BEH C8, 50*2.1 mm
      UPLC column, with a 1.7 MUm particle size and the eluent was analyzed using an
      API 4000 mass analyzer in selected reaction monitoring mode. The method was
      validated as per FDA Bioanalytical Method Validation guidelines. RESULTS: The
      analytical measuring range of the LC-MS/MS method is 0.5-1000 ng/ml. Calibration
      curves were generated using weighted 1/x(2) quadratic regression. Inter-and intra
      assay precision was <=5.38% and <=5.98%, respectively; inter-and intra-assay
      accuracy (%DEV) was <=10.2% and <=8.44%, respectively. Additional studies
      illustrated similar matrix effects between maraviroc and its internal standard,
      and that maraviroc is stable under a variety of conditions. Method comparison
      studies with a reference LC-MS/MS method show a slope of 0.948 with a Spearman
      coefficient of 0.98. CONCLUSIONS: Based on the validation metrics, we have
      generated a sensitive and automated LC-MS/MS method for maraviroc quantification
      in human plasma.

PMID- 24561265
TI  - Tetracycline nanoparticles loaded calcium sulfate composite beads for periodontal
      management.
AB  - BACKGROUND: The objective of this study was to fabricate, characterize and
      evaluate in vitro, an injectable calcium sulfate bone cement beads loaded with an
      antibiotic nanoformulation, capable of delivering antibiotic locally for the
      treatment of periodontal disease. METHODS: Tetracycline nanoparticles (Tet NPs)
      were prepared using an ionic gelation method and characterized using DLS, SEM,
      and FTIR to determine size, morphology, stability and chemical interaction of the
      drug with the polymer. Further, calcium sulfate (CaSO4) control and CaSO4-Tet NP
      composite beads were prepared and characterized using SEM, FTIR and XRD. The drug
      release pattern, material properties and antibacterial activity were evaluated.
      In addition, protein adsorption, cytocompatibility and alkaline phosphatase
      activity of the CaSO4-Tet NP composite beads in comparison to the CaSO4 control
      were analyzed. RESULTS: Tet NPs showed a size range of 130+/-20nm and the
      entrapment efficiency calculated was 89%. The composite beads showed sustained
      drug release pattern. Further the drug release data was fitted into various
      kinetic models wherein the Higuchi model showed higher correlation value
      (R(2)=0.9279) as compared to other kinetic models. The composite beads showed
      antibacterial activity against Staphylococcus aureus and Escherichia coli. The
      presence of Tet NPs in the composite bead didn't alter its cytocompatibility. In
      addition, the composite beads enhanced the ALP activity of hPDL cells.
      CONCLUSIONS: The antibacterial and cytocompatible CaSO4-Tet NP composite beads
      could be beneficial in periodontal management to reduce the bacterial load at the
      infection site. GENERAL SIGNIFICANCE: Tet NPs would deliver antibiotic locally at
      the infection site and the calcium sulfate cement, would itself facilitate tissue
      regeneration.

PMID- 24561266
TI  - TGFbeta and matrix-regulated epithelial to mesenchymal transition.
AB  - BACKGROUND: The progression of cancer through stages that guide a benign
      hyperplastic epithelial tissue towards a fully malignant and metastatic
      carcinoma, is driven by genetic and microenvironmental factors that remodel the
      tissue architecture. The concept of epithelial-mesenchymal transition (EMT) has
      evolved to emphasize the importance of plastic changes in tissue architecture,
      and the cross-communication of tumor cells with various cells in the stroma and
      with specific molecules in the extracellular matrix (ECM). SCOPE OF THE REVIEW:
      Among the multitude of ECM-embedded cytokines and the regulatory potential of ECM
      molecules, this article focuses on the cytokine transforming growth factor beta
      (TGFbeta) and the glycosaminoglycan hyaluronan, and their roles in cancer biology
      and EMT. For brevity, we concentrate our effort on breast cancer. MAJOR
      CONCLUSIONS: Both normal and abnormal TGFbeta signaling can be detected in
      carcinoma and stromal cells, and TGFbeta-induced EMT requires the expression of
      hyaluronan synthase 2 (HAS2). Correspondingly, hyaluronan is a major constituent
      of tumor ECM and aberrant levels of both hyaluronan and TGFbeta are thought to
      promote a wounding reaction to the local tissue homeostasis. The link between EMT
      and metastasis also involves the mesenchymal-epithelial transition (MET). ECM
      components, signaling networks, regulatory non-coding RNAs and epigenetic
      mechanisms form the network of regulation during EMT-MET. GENERAL SIGNIFICANCE:
      Understanding the mechanism that controls epithelial plasticity in the mammary
      gland promises the development of valuable biomarkers for the prognosis of breast
      cancer progression and even provides new ideas for a more integrative therapeutic
      approach against disease. This article is part of a Special Issue entitled Matrix
      mediated cell behaviour and properties.

PMID- 24561267
TI  - Galectin-3 binds to MUC1-N-terminal domain and triggers recruitment of beta
      catenin in MUC1-expressing mouse 3T3 cells.
AB  - BACKGROUND: Galectin-3 is expressed in a variety of tumors and its expression
      level is related with tumor progression. Aberrant expression of MUC1 in various
      tumors is also associated with a poor prognosis. It has been reported that MUC1
      is a natural ligand of galectin-3. METHODS: A stable MUC1 transfectant was
      produced by introducing MUC1 cDNA into mouse 3T3 fibroblasts (MUC1/3T3 cells).
      MUC1 was prepared from MUC1/3T3 cells; MUC1-N-terminal domain (MUC1-ND) and -C
      terminal domain (MUC1-CD) were separated by CsCl ultracentrifugation, and then
      the galectin-3-binding domain was determined by co-immuniprecipitation assay.
      After ligation of galectin-3 to 3T3/MUC1 cells, MUC1-CD was immunoprecipitated
      from the cell lysate. The immunoprecipitate was subjected to SDS-PAGE and Western
      blotting, followed by detection of co-immunoprecipitated beta-catenin. RESULTS:
      Galectin-3 binds to the N-terminal domain of MUC1 but not to the C-terminal one.
      Galectin-3 present on the cell surface increased with the expression of MUC1 and
      is colocalized with MUC1. It should be noted that beta-catenin was detected in
      the immunoprecipitate with anti-MUC1-CD Ab from a lysate of galectin-3-treated
      3T3/MUC1 cells. CONCLUSIONS: Galectin-3 binds to MUC1-ND and triggers MUC1
      mediated signaling in 3T3/MUC1 cells, leading to recruitment of beta-catenin to
      MUC1-CD. GENERAL SIGNIFICANCE: This signaling may be another MUC1-mediated
      pathway and function in parallel with a growth factor-dependent MUC1-mediated
      pathway.

PMID- 24561268
TI  - Molecular and morphological phylogeny of Saccocirridae (Annelida) reveals two
      cosmopolitan clades with specific habitat preferences.
AB  - Saccocirrids are tiny, slender annelids inhabiting the interstices among coarse
      sand sediments in shallow waters. The 22 nominal species can be grouped into two
      morphological groups "papillocercus" and "krusadensis", based on the
      absence/presence of a pharyngeal bulbus muscle, absence/presence of ventral
      ciliary patterns, bilateral/unilateral gonad arrangement and chaetal differences.
      We present herein the first phylogenetic analyses of Saccocirridae based on four
      molecular markers and 34 morphological characters, employing maximum likelihood
      and Bayesian methods. All analyses confirmed the monophyly of each morphological
      group with high nodal support. As a consequence and based on several apomorphic
      characters, a new genus, Pharyngocirrus gen. nov., is erected for the
      "krusadensis" clade. Remarkably, the habitat preferences and trophic guilds are
      also shown to differ between the two genera, yet show strong consistency within
      each group. Geographic distribution analyses underscore the family preference for
      subtropical areas, but reject the previously proposed restriction of
      Pharyngocirrus gen. nov. to the Indo-Pacific. The finding of two morphologically
      diverging, cosmopolitan sister clades with different habitat preferences suggest
      an early ecological diversification of the family, conserved during the later
      evolution, speciation processes and dispersal of the family. 

PMID- 24561269
TI  - Perfluorooctane sulfonate blocked autophagy flux and induced lysosome membrane
      permeabilization in HepG2 cells.
AB  - Perfluorooctane sulfonate (PFOS) is an emerging persistent organic pollutant
      widely distributed in the environment, wildlife and human. In this study, as
      observed under the transmission electron microscope, PFOS increased autophagosome
      numbers in HepG2 cells, and it was confirmed by elevated LC3-II levels in Western
      blot analysis. PFOS increased P62 level and chloroquine failed to further
      increase the expression of LC3-II after PFOS treatment, indicating that the
      accumulation of autophagosome was due to impaired degradation rather than
      increased formation. With acridine orange staining, we found PFOS caused
      lysosomal membrane permeabilization (LMP). In this study, autophasome formation
      inhibitor 3-methyladenine protected cells against PFOS toxicity, autophagy
      stimulator rapamycin further decreased cell viability and increased LDH release,
      cathepsin inhibitor did not influence cell viability of PFOS-treated HepG2 cells
      significantly. These further supported the notion that autophagic cell death
      contributed to PFOS-induced hepatotoxicity. In summary, the data of the present
      study revealed that PFOS induced LMP and consequent blockage of autophagy flux,
      leading to an excessive accumulation of the autophagosomes and turning autophagy
      into a destructive process eventually. This finding will provide clues for
      effective prevention and treatment of PFOS-induced hepatic disease. 

PMID- 24561270
TI  - Polydopamine coating effects on ultrafiltration membrane to enhance power density
      and mitigate biofouling of ultrafiltration microbial fuel cells (UF-MFCs).
AB  - Membrane resistance is due to the low accessibility of liquid electrolytes onto
      the membrane surface; resultant membrane biofouling lowers the power generation
      capacity of microbial fuel cells (MFCs). In this study, in order to reduce
      membrane resistance caused by migrative ion transport resistance and membrane
      biofouling, a polydopamine (PD) coating was adopted for the modification of
      ultrafiltration (UF) membrane surfaces in UF membrane integrated MFCs (UF-MFCs).
      After a PD coating was applied to a UF membrane, the contact angle measured on
      the support layer of a UF membrane decreased and the membrane surface charge
      became negative. The maximum power density of UF-MFC increased after the PD
      coating on a UF membrane and a remarkable reduction of charge transfer resistance
      was observed using electrochemical impedance spectroscopy (EIS) analysis. Lower
      extracellular polymeric substance (EPS) concentrations and total cell numbers
      were observed on the PD coated UF membrane surface after 72 h operation, although
      17% of a permeate flux of UF-MFC decreased after PD coating. 

PMID- 24561272
TI  - Cooking fish is not effective in reducing exposure to perfluoroalkyl and
      polyfluoroalkyl substances.
AB  - Consumption of fish is considered a part of a healthy diet; however, health risks
      from fish consumption exist due to potential exposure to various contaminants
      accumulated in fish. Cooking fish can reduce exposure to many organic chemicals
      in fish. Similar results have been presented for low levels of perfluoroalkyl and
      polyfluoroalkyl substances (PFASs), a class of contaminants of emerging concern,
      in grocery store fish. We examined the effectiveness of three cooking methods
      (i.e., baking, broiling, and frying) on reducing PFAS levels in four sport fish
      species. Samples of Chinook salmon, common carp, lake trout and walleye were
      collected from four rivers in Ontario, Canada and skin-off fillets were analyzed
      for regular groups of PFASs such as perfluoroalkyl carboxylic acids (PFCAs) and
      perfluoroalkane sulfonic acids (PFSAs), as well as perfluoroalkyl phosphonic
      acids (PFPAs), perfluoroalkyl phosphinic acids (PFPIAs) and polyfluoroalkyl
      phosphoric acid diesters (diPAPs), which are PFASs of emerging concern.
      Perfluorooctane sulfonate (PFOS) was the dominant PFAS detected and the
      concentrations were more than an order of magnitude higher than those reported
      for fish from grocery stores in Canada, Spain, and China. Although concentrations
      of PFOS in fish fillets generally increase after cooking, amounts of PFOS largely
      remain unchanged. Relatively minor differences in changes in the fish PFAS
      amounts after cooking depended on fish species and cooking method used. We
      conclude that cooking sport fish is generally not an effective approach to reduce
      dietary exposure to PFASs, especially PFOS. 

PMID- 24561273
TI  - Mitochondrial respiratory chain complexes as sources and targets of thiol-based
      redox-regulation.
AB  - The respiratory chain of the inner mitochondrial membrane is a unique assembly of
      protein complexes that transfers the electrons of reducing equivalents extracted
      from foodstuff to molecular oxygen to generate a proton-motive force as the
      primary energy source for cellular ATP-synthesis. Recent evidence indicates that
      redox reactions are also involved in regulating mitochondrial function via redox
      modification of specific cysteine-thiol groups in subunits of respiratory chain
      complexes. Vice versa the generation of reactive oxygen species (ROS) by
      respiratory chain complexes may have an impact on the mitochondrial redox balance
      through reversible and irreversible thiol-modification of specific target
      proteins involved in redox signaling, but also pathophysiological processes.
      Recent evidence indicates that thiol-based redox regulation of the respiratory
      chain activity and especially S-nitrosylation of complex I could be a strategy to
      prevent elevated ROS production, oxidative damage and tissue necrosis during
      ischemia-reperfusion injury. This review focuses on the thiol-based redox
      processes involving the respiratory chain as a source as well as a target,
      including a general overview on mitochondria as highly compartmentalized redox
      organelles and on methods to investigate the redox state of mitochondrial
      proteins. This article is part of a Special Issue entitled: Thiol-Based Redox
      Processes. 

PMID- 24561274
TI  - Neuropeptide B in Nile tilapia Oreochromis niloticus: molecular cloning and its
      effects on the regulation of food intake and mRNA expression of growth hormone
      and prolactin.
AB  - Neuropeptide B (NPB) regulates food intake, energy homeostasis and hormone
      secretion in mammals via two G-protein coupled receptors, termed as GPR 7 and GPR
      8. However, there is no study that reports the function of NPB in teleosts. In
      this study, the full-length cDNA of prepro-NPB with the size of 663bp was cloned
      from the hypothalamus of Nile tilapia. The CDS of the prepro-NPB is 387bp which
      encodes a precursor protein with the size of 128a.a. This precursor contains a
      mature peptide with the size of 29a.a, and it was named as NPB29. Tissue
      distribution study showed that this gene was mainly expressed in different parts
      of brain, especially in the diencephalon as well as hypothalamus, and the spinal
      cord in Nile tilapia. Fasting significantly stimulated the mRNA expression of NPB
      in the brain area without hypothalamus, and refeeding after fasting for 3 and
      14days also showed similar effects on NPB expression. While, only short-term
      fasting (3days) and refeeding after fasting for 7 and 14days induced mRNA
      expression of NPB in the hypothalamus. Intraperitoneal (i.p.) injection of NPB
      remarkably elevated the mRNA expression of hypothalamic neuropeptide Y (NPY),
      cholecystokinin 1 (CCK1) and pituitary prolactin (PRL), whereas significantly
      inhibited growth hormone (GH) expression in pituitary. These observations in the
      present study suggested that NPB may participate in the regulation of feeding and
      gene expression of pituitary GH and PRL in Nile tilapia. 

PMID- 24561271
TI  - Long-term exposure to elemental constituents of particulate matter and
      cardiovascular mortality in 19 European cohorts: results from the ESCAPE and
      TRANSPHORM projects.
AB  - BACKGROUND: Associations between long-term exposure to ambient particulate matter
      (PM) and cardiovascular (CVD) mortality have been widely recognized. However,
      health effects of long-term exposure to constituents of PM on total CVD mortality
      have been explored in a single study only. AIMS: The aim of this study was to
      examine the association of PM composition with cardiovascular mortality. METHODS:
      We used data from 19 European ongoing cohorts within the framework of the ESCAPE
      (European Study of Cohorts for Air Pollution Effects) and TRANSPHORM (Transport
      related Air Pollution and Health impacts--Integrated Methodologies for Assessing
      Particulate Matter) projects. Residential annual average exposure to elemental
      constituents within particle matter smaller than 2.5 and 10 MUm (PM2.5 and PM10)
      was estimated using Land Use Regression models. Eight elements representing major
      sources were selected a priori (copper, iron, potassium, nickel, sulfur, silicon,
      vanadium and zinc). Cohort-specific analyses were conducted using Cox
      proportional hazards models with a standardized protocol. Random-effects meta
      analysis was used to calculate combined effect estimates. RESULTS: The total
      population consisted of 322,291 participants, with 9545 CVD deaths. We found no
      statistically significant associations between any of the elemental constituents
      in PM2.5 or PM10 and CVD mortality in the pooled analysis. Most of the hazard
      ratios (HRs) were close to unity, e.g. for PM10 Fe the combined HR was 0.96 (0.84
      1.09). Elevated combined HRs were found for PM2.5 Si (1.17, 95% CI: 0.93-1.47),
      and S in PM2.5 (1.08, 95% CI: 0.95-1.22) and PM10 (1.09, 95% CI: 0.90-1.32).
      CONCLUSION: In a joint analysis of 19 European cohorts, we found no statistically
      significant association between long-term exposure to 8 elemental constituents of
      particles and total cardiovascular mortality.

PMID- 24561276
TI  - Chemotaxis behavior toward an odor is regulated by constant sodium chloride
      stimulus in Caenorhabditis elegans.
AB  - We studied the chemotaxis behavior of Caenorhabditis elegans toward a
      chemoattractant in the presence of background sensory stimulus. Chemotaxis toward
      an odor butanone was greater in the presence of sodium chloride (NaCl) than that
      without NaCl. By contrast, chemotaxis toward NaCl was not affected by a butanone
      background. The salt-sensing ASE neuron-deficient che-1(p674) mutants and worms
      with ASE genetically ablated showed high chemotaxis toward butanone, regardless
      of the presence of a NaCl background. Therefore, in wild-type worms, information
      from ASE in the absence of NaCl suppresses butanone chemotaxis, while the
      suppression is removed in the presence of NaCl. 

PMID- 24561275
TI  - Characterization, tissue distribution and regulation by fasting of the agouti
      family of peptides in the sea bass (Dicentrarchus labrax).
AB  - The melanocortin system is one of the most complex hormonal systems in
      vertebrates. Atypically, the signaling of melanocortin receptors is regulated by
      the binding of endogenous antagonists, named agouti-signaling protein (ASIP) and
      agouti-related protein (AGRP). Teleost specific genome duplication (TSGD)
      rendered new gene copies in teleost fish and up to four different genes of the
      agouti family of peptides have been characterized. In this paper, molecular
      cloning was used to characterize mRNA of the agouti family of peptides in sea
      bass. Four different genes were identified: AGRP1, ASIP1, AGRP2 and ASIP2. The
      AGRP1 gene is mainly expressed in the brain whereas ASIP1 is mainly expressed in
      the ventral skin. Both ASIP2 and AGRP2 are expressed in the brain and the pineal
      gland but also in some peripheral tissues. Immunocytochemical studies
      demonstrated that AGRP1 is exclusively expressed within the lateral tuberal
      nucleus, the homologue of the mammalian arcuate nucleus in fish. Long-term
      fasting (8-29 days) increased the hypothalamic expression of AGRP1 but depressed
      AGRP2 expression (15-29 days). In contrast, the hypothalamic expression of ASIP2
      was upregulated during short-term fasting suggesting that this peptide could be
      involved in the short term regulation of food intake in the sea bass.

PMID- 24561277
TI  - Synthesis, characterization, thermal and DNA-binding properties of new zinc
      complexes with 2-hydroxyphenones.
AB  - The neutral mononuclear zinc complexes with 2-hydroxyphenones (ketoH) having the
      formula [Zn(keto)2(H2O)2] and [Zn(keto)2(enR)], where enR stands for a N,N'-donor
      heterocyclic ligand such as 2,2'-bipyridine (bipy), 1,10-phenanthroline (phen) or
      2,2'-dipyridylamine (dpamH), have been synthesized and characterized by IR, UV
      and (1)H NMR spectroscopies. The 2-hydroxyphenones are chelated to the metal ion
      through the phenolate and carbonyl oxygen atoms. The crystal structures of [bis(2
      hydroxy-4-methoxy-benzophenone)(2,2'-bipyridine)zinc(II)] dimethanol solvate and
      [bis(2-hydroxy-benzophenone)(2,2'-bipyridine)zinc(II)] dimethanol solvate have
      been determined by X-ray crystallography. The thermal stability of the zinc
      complexes has been investigated by simultaneous TG/DTG-DTA technique. The ability
      of the complexes to bind to calf-thymus DNA (CT DNA) has been studied by UV
      absorption and fluorescence emission spectroscopy as well as viscosity
      measurements. UV studies of the interaction of the complexes with DNA have shown
      that they can bind to CT DNA and the corresponding binding constants to DNA have
      been calculated and evaluated. The complexes most probably bind to CT DNA via
      intercalation as concluded by studying the viscosity of a DNA solution in the
      presence of the complexes. Competitive studies with ethidium bromide (EB) have
      shown that the reported complexes can displace the DNA-bound EB, suggesting
      strong competition with EB for the intercalation site. 

PMID- 24561278
TI  - On the cytotoxic activity of Pd(II) complexes of N,N-disubstituted-N'-acyl
      thioureas.
AB  - The rational design of anticancer drugs is one of the most promising strategies
      for increasing their cytotoxicity and for minimizing their toxicity. Manipulation
      of the structure of ligands or of complexes represents a strategy for which is
      possible to modify the potential mechanism of their action against the cancer
      cells. Here we present the cytotoxicity of some new palladium complexes and our
      intention is to show the importance of non-coordinated atoms of the ligands in
      the cytotoxicity of the complexes. New complexes of palladium (II), with general
      formulae [Pd(PPh3)2(L)]PF6 or [PdCl(PPh3)(L)], where L=N,N-disubstituted-N'-acyl
      thioureas, were synthesized and characterized by elemental analysis, molar
      conductivity, melting points, IR, NMR((1)H, (13)C and (31)P{(1)H}) spectroscopy.
      The spectroscopic data are consistent with the complexes containing an O, S
      chelated ligand. The structures of complexes with N,N-dimethyl-N'
      benzoylthiourea, N,N-diphenyl-N'-benzoylthiourea, N,N-diethyl-N'-furoylthiourea,
      and N,N-diphenyl-N'-furoylthiourea were determined by X-ray crystallography,
      confirming the coordination of the ligands with the metal through sulfur and
      oxygen atoms, forming distorted square-planar structures. The N,N-disubstituted
      N'-acyl thioureas and their complexes were screened with respect to their
      antitumor cytotoxicity against DU-145 (human prostate cancer cells), MDA-MB-231
      (human breast cancer cells) and their toxicity against the L929 cell line (health
      cell line from mouse). 

PMID- 24561279
TI  - TIDAL WAVES: Network mechanisms in the neuroendocrine control of prolactin
      release.
AB  - Neuroendocrine tuberoinfundibular dopamine (TIDA) neurons tonically inhibit
      pituitary release of the hormone, prolactin. Through the powerful actions of
      prolactin in promoting lactation and maternal behaviour while suppressing sexual
      drive and fertility, TIDA neurons play a key role in reproduction. We summarize
      insights from recent in vitro studies into the membrane properties and network
      behaviour of TIDA neurons including the observations that TIDA neurons exhibit a
      robust oscillation that is synchronized between cells and depends on intact gap
      junction communication. Comparisons are made with phasic firing patterns in other
      neuronal populations. Modulators involved in the control of lactation - including
      serotonin, thyrotropin-releasing hormone and prolactin itself - have been shown
      to change the electrical behaviour of TIDA cells. We propose that TIDA discharge
      mode may play a central role in tuning the amount of dopamine delivered to the
      pituitary and hence circulating prolactin concentrations in different
      reproductive states and pathological conditions. 

PMID- 24561280
TI  - Are vitamins A and D important in the development of food allergy and how are
      they best measured?
AB  - Food allergy has a dramatic impact on a child's (and their family's) quality of
      life and places a major financial burden on the community. It has been
      hypothesized that the increase in food allergy may relate to the concordant rise
      in prevalence of vitamin D insufficiency. More recently a second hypothesis has
      implicated vitamin A sufficiency in the development of immune tolerance.
      Together, these hypotheses have prompted investigation into the circulating
      levels of vitamins A and D in relation to food allergy prevalence. This review
      aims to examine the relationship between vitamins A and D and food allergy. The
      first part of this review presents the available epidemiological data which
      proposes a dramatic increase of food allergy and related anaphylaxis during the
      last two decades. There is some indirect evidence that variation in food allergy
      prevalence within countries might be linked with ambient ultra violet radiation
      exposure and thus potentially with vitamin D levels. Only a few studies to date
      have directly examined the relationship between measured serum vitamin D levels
      and either food sensitization or allergy. The significance of vitamin A in food
      allergy prevalence is only provided through a hypothetical association due to its
      role in the immune system. The second part of this review discusses the relevant
      aspects of the analytical methods to assess vitamin A and D levels in children.
      The primary methods utilized relate to measuring the main circulating forms of
      vitamins A and D in blood i.e. retinol and 25-hydroxy-vitamin-D3 respectively.
      Chromatographic separation coupled with mass spectrometric detection is
      considered the gold standard method for both vitamins. These analytical methods
      should be fully validated for the use in pediatric populations to ensure they are
      fit for their clinical purpose. 

PMID- 24561281
TI  - GDF5 reduces MMP13 expression in human chondrocytes via DKK1 mediated canonical
      Wnt signaling inhibition.
AB  - OBJECTIVE: Growth differentiation factor 5 (GDF5) is important for joint
      formation and associated with osteoarthritis (OA). Its role for the homeostasis
      of cartilage extracellular matrix (ECM) is, however, unknown. The canonical Wnt
      signaling pathway is also implemented in OA and activation of the pathway has
      detrimental effects on the cartilage ECM. The objective of this study was to
      investigate the effect of GDF5 stimulation on the Wnt signaling pathway and on
      the expression of known modulators of cartilage ECM. DESIGN: Human chondrocytes
      were cultured in the pellet mass system and stimulated with increasing
      concentrations of GDF5. Expression of matrix modulating enzymes and canonical Wnt
      inhibitors dickkopf 1 (DKK1) and frizzled related protein (FRZB) were measured
      with quantitative PCR (qPCR). Protein levels of matrix metalloprotease 13
      (MMP13), DKK1 and beta-catenin were measured with enzyme-linked immunosorbent
      assay (ELISA). Canonical Wnt signaling was stimulated with Wnt3a and small
      molecule CHIR-99021 and DKK1 was blocked with small molecule WAY-262611. RESULTS:
      In this study, we show that GDF5 stimulation of human chondrocytes inhibits
      expression of the cartilage ECM degrading enzymes MMP13 and ADAMTS4 and
      stimulates the expression of cartilage anabolic genes ACAN and SOX9. We further
      show that the stimulation inhibits the canonical Wnt signaling pathway through
      expression of the canonical Wnt inhibitors DKK1 and FRZB. Finally we show that
      inhibition of MMP13 expression through GDF5 stimulation is mediated by DKK1.
      CONCLUSION: Herein, we provide evidence of a previously unknown link between GDF5
      signaling and canonical Wnt signaling that may contribute to the understanding of
      the molecular mechanisms of OA.

PMID- 24561283
TI  - Cystic fibrosis: toward personalized therapies.
AB  - Cystic fibrosis (CF), the most common, life-threatening monogenetic disease in
      Caucasians, is caused by mutations in the CFTR gene, encoding a cAMP- and cGMP
      regulated epithelial chloride channel. Symptomatic therapies treating end-organ
      manifestations have increased the life expectancy of CF patients toward a mean of
      40 years. The recent development of CFTR-targeted drugs that emerged from high
      throughput screening and are capable of correcting the basic defect promises to
      transform the therapeutic landscape from a trial-and-error prescription to
      personalized medicine. This stratified approach is tailored to a specific
      functional class of mutations in CFTR, but can be refined further to an
      individual level by exploiting recent advances in ex vivo drug testing methods.
      These tests range from CFTR functional measurements in rectal biopsies donated by
      a CF patient to the use of patient-derived intestinal or pulmonary organoids.
      Such organoids may serve as an inexhaustible source of epithelial cells that can
      be stored in biobanks and allow medium- to high-throughput screening of CFTR
      activators, correctors and potentiators on the basis of a simple microscopic
      assay monitoring organoid swelling. Thus the recent breakthrough in stem cell
      biology allowing the culturing of mini-organs from individual patients is not
      only relevant for future stem cell therapy, but may also allow the preclinical
      testing of new drugs or combinations that are optimally suited for an individual
      patient.

PMID- 24561282
TI  - FK506 protects against articular cartilage collagenous extra-cellular matrix
      degradation.
AB  - OBJECTIVE: Osteoarthritis (OA) is a non-rheumatologic joint disease characterized
      by progressive degeneration of the cartilage extra-cellular matrix (ECM),
      enhanced subchondral bone remodeling, activation of synovial macrophages and
      osteophyte growth. Inhibition of calcineurin (Cn) activity through tacrolimus
      (FK506) in in vitro monolayer chondrocytes exerts positive effects on ECM marker
      expression. This study therefore investigated the effects of FK506 on anabolic
      and catabolic markers of osteoarthritic chondrocytes in 2D and 3D in vitro
      cultures, and its therapeutic effects in an in vivo rat model of OA. METHODS:
      Effects of high and low doses of FK506 on anabolic (QPCR/histochemistry) and
      catabolic (QPCR) markers were evaluated in vitro on isolated (2D) and ECM
      embedded chondrocytes (explants, 3D pellets). Severe cartilage damage was induced
      unilaterally in rat knees using papain injections in combination with a moderate
      running protocol. Twenty rats were treated with FK506 orally and compared to
      twenty untreated controls. Subchondral cortical and trabecular bone changes
      (longitudinal microCT) and macrophage activation (SPECT/CT) were measured.
      Articular cartilage was analyzed ex vivo using contrast enhanced microCT and
      histology. RESULTS: FK506 treatment of osteoarthritic chondrocytes in vitro
      induced anabolic (mainly collagens) and reduced catabolic ECM marker expression.
      In line with this, FK506 treatment clearly protected ECM integrity in vivo by
      markedly decreasing subchondral sclerosis, less development of subchondral pores,
      depletion of synovial macrophage activation and lower osteophyte growth.
      CONCLUSION: FK506 protected cartilage matrix integrity in vitro and in vivo.
      Additionally, FK506 treatment in vivo reduced OA-like responses in different
      articular joint tissues and thereby makes Cn an interesting target for
      therapeutic intervention of OA.

PMID- 24561284
TI  - Early cystic fibrosis lung disease: Role of airway surface dehydration and
      lessons from preventive rehydration therapies in mice.
AB  - Cystic fibrosis (CF) lung disease starts in the first months of life and remains
      one of the most common fatal hereditary diseases. Early therapeutic interventions
      may provide an opportunity to prevent irreversible lung damage and improve
      outcome. Airway surface dehydration is a key disease mechanism in CF, however,
      its role in the in vivo pathogenesis and as therapeutic target in early lung
      disease remains poorly understood. Mice with airway-specific overexpression of
      the epithelial Na(+) channel (betaENaC-Tg) recapitulate airway surface
      dehydration and phenocopy CF lung disease. Recent studies in neonatal betaENaC-Tg
      mice demonstrated that airway surface dehydration produces early mucus plugging
      in the absence of mucus hypersecretion, which triggers airway inflammation,
      promotes bacterial infection and causes early mortality. Preventive rehydration
      therapy with hypertonic saline or amiloride effectively reduced mucus plugging
      and mortality in neonatal betaENaC-Tg mice. These results support clinical
      testing of preventive/early rehydration strategies in infants and young children
      with CF. 

PMID- 24561285
TI  - The rRNA and tRNA transcripts of maternally and paternally inherited
      mitochondrial DNAs of Mytilus galloprovincialis suggest presence of a
      "degradosome" in mussel mitochondria and necessitate the re-annotation of the l
      rRNA/CR boundary.
AB  - Species of the genus Mytilus carry two mitochondrial genomes in obligatory
      coexistence; one transmitted though the eggs (the F type) and one through the
      sperm (the M type). We have studied the 3' and 5' ends of rRNA and tRNA
      transcripts using RT-PCR and RNA circularization techniques in both the F and M
      genomes of Mytilus galloprovincialis. We have found polyadenylated and non
      adenylated transcripts for both ribosomal and transfer RNAs. In all these genes
      the 5' ends of the transcripts coincided with the first nucleotide of the
      annotated genes, but the 3' ends were heterogeneous. The l-rRNA 3' end is 47 or
      48 nucleotides upstream from the one assigned by a previous annotation, which
      makes the adjacent first domain (variable domain one, VD1) of the main control
      region (CR) correspondingly longer. We have observed s-rRNA and l-rRNA
      transcripts with truncated 3' end and polyadenylated tRNA transcripts carrying
      the CCA trinucleotide. We have also detected polyadenylated RNA remnants carrying
      the sequences of the control region, which strongly suggests RNA degradation
      activity and thus presence of degradosomes in Mytilus mitochondria. 

PMID- 24561286
TI  - Candidate agents for pancreatic ductal adenocarcinoma identified by a sub-pathway
      based method.
AB  - AIM: Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer death
      worldwide. This study aims to explore the molecular mechanism of PDAC and
      identify biologically active small molecules capable of targeting the sub
      pathways which were dysregulated in the development of PDAC. METHODS: The gene
      expression profile of GSE28735 microarray data (including 45 matching pairs of
      pancreatic tumor and adjacent non-tumor tissues) was downloaded from GEO (Gene
      Expression Omnibus) database. Differentially expressed genes (DEGs) between
      pancreatic tumor tissues and non-tumor tissues were identified, and then the sub
      pathway enrichment analysis was performed. Moreover, an approach based on
      targeting sub-pathways was used to reveal potential agents for PDAC. RESULTS: A
      total of 5315 DEGs were identified between pancreatic tumor tissues and non-tumor
      tissues with a false discovery rate of 0.01. Genes of collagen family and
      integrin receptor family which were involved in pathways of focal adhesion and
      ECM-receptor interaction respectively were differentially expressed in the
      pancreatic tumor tissue. Besides, a total of 85 small molecules including
      fludrocortisone, latamoxef and metronidazole were revealed by bioinformatics
      analysis. CONCLUSION: This study proposed the use of an approach based on
      targeting sub-pathways to identify potential agents for PDAC. The sub-pathways
      and small molecules discovered in this study were not only related to PDAC but
      also play a role in perturbing the development of PDAC.

PMID- 24561287
TI  - Hepcidin deficiency undermines bone load-bearing capacity through inducing iron
      overload.
AB  - Osteoporosis is one of the leading disorders among aged people. Bone loss results
      from a number of physiological alterations, such as estrogen decline and aging.
      Meanwhile, iron overload has been recognized as a risk factor for bone loss.
      Systemic iron homeostasis is fundamentally governed by the hepcidin-ferroportin
      regulatory axis, where hepcidin is the key regulator. Hepcidin deficiency could
      induce a few disorders, of which iron overload is the most representative
      phenotype. However, there was little investigation of the effects of hepcidin
      deficiency on bone metabolism. To this end, hepcidin-deficient (Hamp1(-/-)) mice
      were employed to address this issue. Our results revealed that significant iron
      overload was induced in Hamp1(-/-) mice. Importantly, significant decreases of
      maximal loading and maximal bending stress were found in Hamp1(-/-) mice relative
      to wildtype (WT) mice. Moreover, the levels of the C-telopeptide of type I
      collagen (CTX-1) increased in Hamp1(-/-) mice. Therefore, hepcidin deficiency
      resulted in a marked reduction of bone load-bearing capacity likely through
      enhancing bone resorption, suggesting a direct correlation between hepcidin
      deficiency and bone loss. Targeting hepcidin or the pathway it modulates may thus
      represent a therapeutic for osteopenia or osteoporosis. 

PMID- 24561288
TI  - The BRC canopy: an important player in bone remodeling.
AB  - This Commentary highlights the article by Andersen et al, which describes
      structural changes in bone associated with increased bone resorption in
      osteoporotic post-menopausal women.

PMID- 24561289
TI  - Microorganisms associated particulate matter: a preliminary study.
AB  - This study aims to determine the microbiological quality of particulate matter
      (PM) in an urban area in Jeddah, Saudi Arabia, during December 2012 to April
      2013. This was achieved by the determination of airborne bacteria, fungi, and
      actinobacteria associated PM10 and PM2.5, as well as their relationships with
      gaseous pollutants, O3, SO2 and NO2, and meteorological factors (T degrees C, RH%
      and Ws). High volume samplers with PM10 and PM2.5 selective sizes, and glass
      fiber filters were used to collect PM10 and PM2.5, respectively. The filters were
      suspended in buffer phosphate and aliquots were spread plated onto the surfaces
      of trypticase soy agar, malt extract agar, and starch casein agar media for
      counting of bacteria, fungi and actinobacteria-associated PM, respectively. PM10
      and PM2.5 concentrations averaged 159.9 MUg/m(3) and 60 MUg/m(3), respectively,
      with the ratio of PM2.5/PM10 averaged ~0.4. The concentrations of O3, SO2 and NO2
      averaged 35.73 MUg/m(3), 38.1MUg/m(3) and 52.5 MUg/m(3), respectively. Fungi and
      actinobacteria associated PM were found in lower concentrations than bacteria.
      The sum of microbial loads was higher in PM10 than PM2.5, however a significant
      correlation (r=0.57, P <= 0.05) was found between the sum of microbial loads
      associated PM10 and PM2.5. Aspergillus fumigatus and Aspergillus niger were the
      common fungal types associated PM. Temperature significantly correlated with both
      PM10 (r=0.44), and PM2.5 (r=0.5). Significant negative correlations were found
      between O3 and PM2.5 (r=-0.47), and between SO2 with PM10 (r=-0.48). Wind speed
      positively correlated with airborne microorganisms associated PM. The regression
      model showed that the inverse PM2.5 concentration (1/PM2.5) was a significant
      determinant of fungal count associated PM. Chemical processes and environmental
      factors could affect properties of PM and in turn its biological quality.

PMID- 24561290
TI  - Contamination and risk assessment (based on bioaccessibility via ingestion and
      inhalation) of metal(loid)s in outdoor and indoor particles from urban centers of
      Guangzhou, China.
AB  - Road dust, household air-conditioning (AC) filter dust and PM2.5 were collected
      to investigate the contamination of metal(loid)s (Cr, Mn, Ni, Cu, Zn, As, Cd, Sn,
      Sb, Hg and Pb) in outdoor and indoor urban environments of Guangzhou. Zinc was
      found to be the most abundant element in road dust and household PM2.5, while the
      concentration of Pb was the highest in AC filter dust. Enrichment factor (EF) was
      used to assess the influence of human activity on the contamination of these
      metal(loid)s. Ingestion and inhalation were the two exposure pathways applied for
      risk assessment. Physiologically based extraction test (PBET) was used to
      estimate the oral bioaccessibilities of metal(loid)s in road dust and AC filter
      dust. Respiratory bioaccessible fraction of metal(loid)s via household PM2.5 was
      extracted with lung simulating solution. Household AC filter dust was more
      hazardous to human health than road dust, especially to children. Arsenic was
      found to be the most risky element based on the risk assessment. 

PMID- 24561291
TI  - Aided phytostabilization using Miscanthus sinensis * giganteus on heavy metal
      contaminated soils.
AB  - A field experiment was carried out to evaluate the use of red mud, a by-product
      of the alumina industry, as a soil amendment on highly contaminated soils in the
      vicinity of a former Pb-Zn smelter in Copsa Mica (Romania). Changes in the
      distribution of Zn, Cd and Pb in various soil fractions, mobility of heavy metals
      in the soil, and their uptake and effects on growth and productivity of
      Miscanthus sinensis * giganteus were evaluated. Uptake of Zn, Cd and Pb was
      determined in different tissues of M. sinensis * giganteus cultivated in field
      plots situated at increasing distance from the pollution source and with
      different levels of contamination and metal availabilities. Soluble metal
      concentrations were determined in centrifugates, whereas potentially soluble
      fractions were analyzed by diffusive gradients in thin films. In terms of the
      biomass productivity there were significant differences among the plants obtained
      in plots with different characteristics and pollution levels. Bioconcentration
      factors were much lower than 1, indicating that M. sinensis * giganteus is an
      excluder of heavy metals, especially Pb. Amending soils with red mud reduced the
      exchangeable or phytoavailable fractions of Zn, Cd and Pb. Overall the results
      suggest that M. sinensis * giganteus is a valuable energy plant and can be
      successfully grown on heavily contaminated soils with Zn, Cd and Pb. Moreover,
      the addition of red mud to these soils can lead to a significant decrease in the
      concentration of heavy metals in the soil and in metal uptake by plant tissues.

PMID- 24561292
TI  - Spray drift reduction under Southern European conditions: a pilot study in the
      Ecopest Project in Greece.
AB  - The objective of this work was to generate spray drift data from pesticide
      application in the field comparing spray drift from traditional equipment with
      emerging, anti-drift technologies. The applications were carried out in the
      Kopais area in central Greece. Currently few data exist as regards to pesticide
      spray drift in Southern European conditions. This work details the data for
      ground and airborne deposition of spray drift using the methodology developed in
      the UK by the Food and Environment Research Agency (FERA). Three trials were
      performed in two days using sunset yellow dye which deposited on dosimeters
      placed at specific distances from the edge of the sprayer boom. The application
      was carried out with a tractor mounted boom sprayer, which was of local
      manufacture, as were the nozzles of Trial I, being flat fan brass nozzles. For
      Trials II and III anti-drift nozzles were used. The boom sprayers were used with
      the settings as employed by the farmers for the routine pesticide applications.
      The results of this work indicate that drift was significantly reduced when anti
      drift nozzles were utilized. 

PMID- 24561293
TI  - Multi-scale geospatial agroecosystem modeling: a case study on the influence of
      soil data resolution on carbon budget estimates.
AB  - The development of effective measures to stabilize atmospheric CO2 concentration
      and mitigate negative impacts of climate change requires accurate quantification
      of the spatial variation and magnitude of the terrestrial carbon (C) flux.
      However, the spatial pattern and strength of terrestrial C sinks and sources
      remain uncertain. In this study, we designed a spatially-explicit agroecosystem
      modeling system by integrating the Environmental Policy Integrated Climate (EPIC)
      model with multiple sources of geospatial and surveyed datasets (including crop
      type map, elevation, climate forcing, fertilizer application, tillage type and
      distribution, and crop planting and harvesting date), and applied it to examine
      the sensitivity of cropland C flux simulations to two widely used soil databases
      (i.e. State Soil Geographic-STATSGO of a scale of 1:250,000 and Soil Survey
      Geographic-SSURGO of a scale of 1:24,000) in Iowa, USA. To efficiently execute
      numerous EPIC runs resulting from the use of high resolution spatial data (56m),
      we developed a parallelized version of EPIC. Both STATSGO and SSURGO led to
      similar simulations of crop yields and Net Ecosystem Production (NEP) estimates
      at the State level. However, substantial differences were observed at the county
      and sub-county (grid) levels. In general, the fine resolution SSURGO data
      outperformed the coarse resolution STATSGO data for county-scale crop-yield
      simulation, and within STATSGO, the area-weighted approach provided more accurate
      results. Further analysis showed that spatial distribution and magnitude of
      simulated NEP were more sensitive to the resolution difference between SSURGO and
      STATSGO at the county or grid scale. For over 60% of the cropland areas in Iowa,
      the deviations between STATSGO- and SSURGO-derived NEP were larger than 1MgCha(
      1)yr(-1), or about half of the average cropland NEP, highlighting the significant
      uncertainty in spatial distribution and magnitude of simulated C fluxes resulting
      from differences in soil data resolution.

PMID- 24561294
TI  - Black carbon aerosol characterization in a remote area of Qinghai-Tibetan
      Plateau, western China.
AB  - The concentrations, size distributions, and mixing states of refractory black
      carbon (rBC) aerosols were measured with a ground-based Single Particle Soot
      Photometer (SP2), and aerosol absorption was measured with an Aethalometer at
      Qinghai Lake (QHL), a rural area in the Northeastern Tibetan Plateau of China in
      October 2011. The area was not pristine, with an average rBC mass concentration
      of 0.36 MUg STP-m(-3) during the two-week campaign period. The rBC concentration
      peaked at night and reached the minimal in the afternoon. This diurnal cycle of
      concentration is negatively correlated with the mixed layer depth and
      ventilation. When air masses from the west of QHL were sampled in late afternoon
      to early evening, the average rBC concentration of 0.21 MUg STP-m(-3) was
      observed, representing the rBC level in a larger Tibetan Plateau region because
      of the highest mixed layer depth. A lognormal primary mode with mass median
      diameter (MMD) of ~175 nm, and a small secondary lognormal mode with MMD of 470
      500 nm of rBC were observed. Relative reduction in the secondary mode during a
      snow event supports recent work that suggested size dependent removal of rBC by
      precipitation. About 50% of the observed rBC cores were identified as thickly
      coated by non-BC material. A comparison of the Aethalometer and SP2 measurements
      suggests that non-BC species significantly affect the Aethalometer measurements
      in this region. A scaling factor for the Aethalometer data at a wavelength of 880
      nm is therefore calculated based on the measurements, which may be used to
      correct other Aethalometer datasets collected in this region for a more accurate
      estimate of the rBC loading. The results present here significantly improve our
      understanding of the characteristics of rBC aerosol in the less studied Tibetan
      Plateau region and further highlight the size dependent removal of BC via
      precipitation.

PMID- 24561295
TI  - Impact of the disposal and re-use of fly ash on water quality: the case of the
      Koradi and Khaperkheda thermal power plants (Maharashtra, India).
AB  - An increasing amount of fly ash from thermal power plants is produced in India
      every year. Its disposal is generally done in ponds after it is mixed together in
      suitable proportion of water to form a slurry. Fly ash from Koradi and
      Khaperkheda thermal power plants (Nagpur, Maharashtra) is commonly disposed in an
      area characterized by the presence of many small villages where the population
      uses the groundwater for drinking and domestic purposes. Here, the groundwater
      locally exceeds the concentration limits recommended by the Bureau of Indian
      Standards (BIS, 2005) and by the World Health Organization (WHO, 2008) for
      Mg(2+), Ca(2+), NO3(-), SO4(2-), Total Dissolved Solids (TDS) and for some minor
      elements like As, Mo, V and U. A new geological map of the study area has been
      prepared to understand the possible water-rock interactions. An extensive
      geochemical survey of groundwater, stream water and fly ash was also carried out
      to clarify the possible origin of the pollutants by discriminating between
      geogenic and anthropogenic sources and to assess the influence of the ash ponds
      on water quality. The analytical results suggest that a large part of the
      sulfates in the groundwater of the villages of Masada, Khairi and Kawatha
      originate from the infiltration of industrial water from tens of factories that
      mix fly ash with relatively high quantities of gypsum and lime for the production
      of bricks. In addition, the interaction with the relatively U-rich Gondwana
      units, like Talchir formation, is probably the cause of the high concentration of
      this element. Results showed how the relatively high concentrations of Mo, As, B
      and F in circulating waters are linked to the leaching from fly ash, also
      pointing out a direct spatial correlation between the concentration of fluorides
      in the groundwater and their closeness to the ash ponds.

PMID- 24561296
TI  - An approach to a black carbon emission inventory for Mexico by two methods.
AB  - A black carbon (BC) emission inventory for Mexico is presented. Estimate was
      performed by using two approaches, based on fuel consumption and emission factors
      in a top-down scheme, and the second from PM25 emission data and its correlation
      with black carbon by source category, assuming that black carbon=elemental
      carbon. Results show that black carbon emissions are in interval 53-473Gg using
      the fuel consumption approach and between 62 and 89 using the sector method.
      Black carbon key sources come from biomass burning in the rural sector, with 47
      percent share to the National total. Mobile sources emissions account to 16% to
      the total. An opportunity to reduce, in the short-term, carbon dioxide equivalent
      (CO2-eq) emissions by reducing black carbon emissions would be obtained in
      reducing emissions mainly from biomass burning in rural housing sector and diesel
      emissions in the transport sector with important co-benefits in direct radiative
      forcing, public health and air quality. 

PMID- 24561297
TI  - Evaluation of PCBs and DDTs in endemic Iberian barbel Barbus bocagei
      (Steindachner, 1864) populations.
AB  - PCB and DDT levels were evaluated in populations of endemic Iberian barbel
      (Barbus bocagei) in the Jarama River in Spain via a pollution gradient from well
      preserved areas upstream to contaminated downstream areas. Age structure,
      abundance, recruitment and levels of morphological abnormalities and
      ectoparasites were assessed. Upstream to downstream PCB concentrations ranged
      from 3.4 to 101.4 ng/g (ww) and from 0.9 to 19.6 ng/g ww for DDTs. The PCB
      pattern was dominated by the PCB 153, 138 and 180 congeners, and the less
      chlorinated ones had a relatively high contribution upstream. Barbels exposed to
      low PCB and DDT levels had a well-balanced population with a predominant cohort
      of young fish, indicating good recruitment. The most contaminated sites displayed
      a disrupted age distribution, where the proportion of young fish was clearly
      under-represented. Recruitment and total density of barbel populations decreased
      downstream where the highest PCB and DDT levels were found. In addition, a higher
      incidence of abnormalities and ectoparasites was observed at these sites. High
      concentrations of PCBs and DDTs most likely contribute to the reduction of
      Iberian barbel reproductive performance in the most contaminated sites, as shown
      by the disrupted age-distribution found in our study.

PMID- 24561298
TI  - Evaluation of the anthropogenic input of caffeine in surface waters of the north
      and center of Portugal by ELISA.
AB  - This study comprises the development of an enzyme-linked immunosorbent assay
      (ELISA) for the quantification of caffeine in complex aqueous matrices without
      any sample clean-up procedure. Salinity and dissolved organic matter were
      selected as potential interfering agents. The addition of a sample buffer
      containing bovine serum albumin (BSA) prior to the sample was found to decrease
      the influence of those interfering agents. The working range of the developed
      method was 0.1-100 MUg L(-1). Quantification of caffeine was possible in 43 out
      of 51 real aqueous samples, at values between <LOD and 15 MUg L(-1). Results
      correlate well with those obtained by LC-MS/MS. To the best of our knowledge this
      is the first study dealing with the quantification of caffeine in Portugal's
      surface waters.

PMID- 24561299
TI  - Effectiveness of a substituted beta-cyclodextrin to prevent cyclosarin toxicity
      in vivo.
AB  - Standard treatment of poisoning by organophosphorus (OP) nerve agents with
      atropine and an oxime has a limited efficacy. An alternative approach is the
      development of stoichiometric or catalytic (bio-)scavengers which should be able
      to prevent systemic toxicity. Recently, a beta-cyclodextrin derivative, 6-OxP-CD,
      bearing a pyridinium oximate in 6-position of one glucose unit was synthetized
      and shown to possess a promising detoxification potential against a variety of
      alkyl methylfluorophosphonates in vitro. In order to investigate the suitability
      of 6-OxP-CD as a small molecule scavenger an in vivo guinea pig model was
      established to determine the protective effect of 6-OxP-CD against the highly
      toxic nerve agent cyclosarin. Prophylactic i.v. injection of 6-OxP-CD (100mg/kg)
      prevented systemic toxicity in cyclosarin (~2LD50) poisoned guinea pigs,
      preserved brain acetylcholinesterase (AChE) activity but did not protect
      erythrocyte AChE activity. A lower 6-OxP-CD dose (50mg/kg) reduced systemic
      toxicity and prevented mortality in all animals. Thus, the results of this proof
      of concept study indicate that 6-OxP-CD may be considered as a potential small
      molecule scavenger to protect against the toxic effects of a range of highly
      toxic OP nerve agents. 

PMID- 24561301
TI  - Musculoskeletal disorders.

PMID- 24561300
TI  - Coumarin derivatives, but not coumarin itself, cause skin irritation via topical
      delivery.
AB  - Coumarin and its derivatives are widely employed as a fragrance in cosmetics and
      skin care products. The skin absorption level and possible disruption to the skin
      by topical application of coumarins were evaluated in this study. Percutaneous
      absorption of osthole, daphnoretin, coumarin, byakangelicin, and 7
      hydroxycoumarin was assessed in vitro and in vivo. Skin physiology measurements
      and immunoblotting were utilized as methodologies for validating toxicity. The
      relationship between structures and permeation/toxicity of coumarins was
      elucidated. Both equimolar concentration and saturated solubility in 30% ethanol
      were used as the applied dose. Osthole with the most lipophilic characteristic
      demonstrated the greatest skin accumulation, followed by coumarin and 7
      hydroxycoumarin. Coumarin was the permeant with the highest flux across the skin.
      The trend of in vivo deposition was consistent with that of the in vitro
      profiles. Skin uptake of osthole was 8-fold higher than that of coumarin. Hair
      follicles played a significant role as a pathway for transport of coumarin
      according to the examination of follicular accumulation. Osthole and 7
      hydroxycoumarin slightly, but significantly, enhanced transepidermal water loss
      after a consecutive 5-day administration. The immunoblotting profiling verified
      the role of proliferation in skin damage induced by osthole, byakangelicin, and 7
      hydroxycoumarin. The proliferation-related proteins examined in this work
      included glucose-regulated proteins, cytokeratin, and C-myc. Daphnoretin and
      coumarin showed a negligible alteration on protein biomarkers. The experimental
      results suggested that skin irritation caused by coumarins was mainly derived
      from the analogs but not from coumarin itself. 

PMID- 24561302
TI  - Phenomena of awareness in dementia: heterogeneity and its implications.
AB  - Despite much research on the relationship between awareness and dementia little
      can be concluded concerning their relationship and the role of other factors. It
      is likely that studies capture different phenomena of awareness. This study aimed
      at identifying and delineating such variation by analysing data from three
      questionnaires obtained during the longitudinal study of awareness in 101 people
      with early-stage dementia. The data concerned awareness in relation to memory,
      activities of daily living and socio-emotional function. Significant differences
      in patterns of discrepancies were obtained. This suggests that the awareness
      phenomena involved were structurally different; and that, in turn, this may
      reflect variation in the intrinsic linking between awareness and its 'object'
      (different 'objects' determining different kinds of judgements). The
      identification of such differences is necessary so that appropriate methodologies
      can be applied to the study of awareness in different contexts. 

PMID- 24561303
TI  - Photochemotherapy using natural anthraquinones: Rubiadin and Soranjidiol
      sensitize human cancer cell to die by apoptosis.
AB  - Over the past decade the science has studied synthetic photosensitizers used in
      photodynamic therapy (PDT) or photochemotherapy as anticancer candidates. In this
      context, compounds extracted from vegetable species present interesting potential
      in the cancer field. In our laboratory, we studied Heterophyllaea pustulata a
      phototoxic shrub that habit the northwest of Argentina. From this vegetal, by in
      vitro germination, we obtained Rubiadin and Soranjidiol, two anthraquinones that
      exhibited significant photocytotoxicity on human cancer cells. In addition, the
      fraction obtained from callus cultures allowed us to get a satisfactory content
      of these compounds compared to those found from the original plant. Under PDT
      regimen, we found that cell destruction resulted in a dose-dependent manner and
      occasioned apoptosis on photosensitized cells. Biochemical analysis revealed the
      involvement of caspase-3, PARP cleavage and DNA fragmentation in Rubiadin induced
      apoptosis. Moreover, Soranjidiol-PDT led to MU-calpain-induced apoptosis
      involving caspases-3-independent DNA fragmentation. We also showed that both
      anthraquinones are cytoplasmatically distributed and out of nucleus. In addition,
      we demonstrated a synergic cytotoxic effect when we combined them. Our data
      demonstrated that Rubiadin and Soranjidiol could be further considered as natural
      photocytotoxic compounds against cancer cells and callus cultures are a plausible
      source of these anthraquinonic compounds. 

PMID- 24561304
TI  - Successful treatment of oral verrucous hyperplasia with photodynamic therapy
      combined with cryotherapy--report of 3 cases.
AB  - Our previous study showed successful treatment of a large oral verrucous
      hyperplasia (OVH) with topical 5-aminolevulinic acid-mediated photodynamic
      therapy combined with cryotherapy (ALA-PDT). In this case series, we extended
      this combined method for another three OVH lesions in three different patients.
      The clinical procedure was conducted as follows: the OVH lesions were irradiated
      with a 635-nm laser 1.5h after topical application of 20% ALA on the lesion for a
      total of 1000 s, which consisted of five 3-min and one 100-s irradiations
      separated by five 3-min rests. Cryogun cryotherapy was then performed on the
      lesion after ALA-PDT. The tumor was cleared after 1-6 treatments. No recurrence
      of the lesion was found after a follow-up period of 6-24 months. We suggest that
      our combined treatment protocol may be effective in treating OVH lesions.

PMID- 24561306
TI  - Amelioration of lipopolysaccharide-induced acute kidney injury by erythropoietin:
      involvement of mitochondria-regulated apoptosis.
AB  - Sepsis remains the most important cause of acute kidney injury (AKI) in
      critically ill patients and is an independent predictor of poor outcome. The
      administration of lipopolysaccharide (LPS) to animals reproduces most of the
      clinical features of sepsis, including AKI, a condition associated with renal
      cellular dysfunction and apoptosis. Erythropoietin (EPO) is a well known
      cytoprotective multifunctional hormone, which exerts anti-inflammatory, anti
      oxidant, anti-apoptotic and angiogenic effects in several tissues. The aim of
      this study was to evaluate the underlying mechanisms of EPO renoprotection
      through the expression of the EPO receptor (EPO-R) and the modulation of the
      intrinsic apoptotic pathway in LPS-induced AKI. Male inbred Balb/c mice were
      divided in four experimental groups: Control, LPS (8 mg/kg i.p.), EPO (3000 IU
      sc) and LPS+EPO. Assessment of renal function, histological examination, TUNEL in
      situ assay, immunohistochemistry and Western blottings of caspase-3, Bax, Bcl-xL,
      EPO-R and Cytochrome c were performed at 24h post treatment. LPS+EPO treatment
      significantly improved renal function and ameliorated histopathological injury
      when compared to the LPS treated group. Results showed that EPO treatment
      attenuates renal tubular apoptosis through: (a) the overexpression of EPO-R in
      tubular interstitial cells, (b) the reduction of Bax/Bcl-xL ratio, (c) the
      inhibition Cytochrome c release into the cytosol and (d) the decrease of the
      active caspase-3 expression. This study suggests that EPO exerts renoprotection
      on an experimental model of LPS-induced AKI. EPO induced renoprotection involves
      an anti-apoptotic effect through the expression of EPO-R and the regulation of
      the mitochondrial apoptotic pathway.

PMID- 24561307
TI  - The progress and future of enhancing antiviral capacity by transgenic technology
      in the silkworm Bombyx mori.
AB  - Bombyx mori is a common lepidopteran model and an important economic insect for
      silk production. B. mori nucleopolyhedrovirus (BmNPV) is a typical pathogenic
      baculovirus that causes serious economic losses in sericulture. B. mori and BmNPV
      are a model of insect host and pathogen interaction including invasion of the
      host by the pathogen, host response, and enhancement of host resistance. The
      antiviral capacity of silkworms can be improved by transgenic technology such as
      overexpression of an endogenous or exogenous antiviral gene, RNA interference of
      the BmNPV gene, or regulation of the immune pathway to inhibit BmNPV at different
      stages of infection. Antiviral capacity could be further increased by combining
      different methods. We discuss the future of an antiviral strategy in silkworm,
      including possible improvement of anti-BmNPV, the feasibility of constructing
      transgenic silkworms with resistance to multiple viruses, and the safety of
      transgenic silkworms. The silkworm model could provide a reference for disease
      control in other organisms.

PMID- 24561305
TI  - A type I interferon transcriptional signature precedes autoimmunity in children
      genetically at risk for type 1 diabetes.
AB  - Diagnosis of the autoimmune disease type 1 diabetes (T1D) is preceded by the
      appearance of circulating autoantibodies to pancreatic islets. However, almost
      nothing is known about events leading to this islet autoimmunity. Previous
      epidemiological and genetic data have associated viral infections and antiviral
      type I interferon (IFN) immune response genes with T1D. Here, we first used DNA
      microarray analysis to identify IFN-beta-inducible genes in vitro and then used
      this set of genes to define an IFN-inducible transcriptional signature in
      peripheral blood mononuclear cells from a group of active systemic lupus
      erythematosus patients (n = 25). Using this predefined set of 225 IFN signature
      genes, we investigated the expression of the signature in cohorts of healthy
      controls (n = 87), patients with T1D (n = 64), and a large longitudinal birth
      cohort of children genetically predisposed to T1D (n = 109; 454 microarrayed
      samples). Expression of the IFN signature was increased in genetically
      predisposed children before the development of autoantibodies (P = 0.0012) but
      not in patients with established T1D. Upregulation of IFN-inducible genes was
      transient, temporally associated with a recent history of upper respiratory tract
      infections (P = 0.0064), and marked by increased expression of SIGLEC-1 (CD169),
      a lectin-like receptor expressed on CD14(+) monocytes. DNA variation in IFN
      inducible genes altered T1D risk (P = 0.007), as exemplified by IFIH1, one of the
      genes in our IFN signature for which increased expression is a known risk factor
      for disease. These findings identify transient increased expression of type I IFN
      genes in preclinical diabetes as a risk factor for autoimmunity in children with
      a genetic predisposition to T1D. 

PMID- 24561309
TI  - Chiral liquid chromatography resolution and stereoselective pharmacokinetic study
      of pioglitazone enantiomers in rats.
AB  - A selective chiral high performance liquid chromatographic (HPLC) method was
      developed and validated to separate and quantify the pioglitazone enantiomers in
      rat plasma. After extraction of the plasma samples with ethyl acetate, the
      separation of pioglitazone enantiomers and internal standard (I.S., dexamethasone
      acetate) was achieved on a cellulose tris (3,5-dichlorophenylcarbamate) column
      known as Chiralpak IC with a mobile phase of hexane-isopropanol (70:30, v/v) at a
      flow rate of 1.0mL/min. The ultraviolet (UV) detection wavelength was set at
      225nm. Baseline separation of pioglitazone enantiomers and I.S., free from
      endogenous interferences, was achieved in less than 25min. Ratio of peak area of
      each enantiomer to I.S. was used for quantification of plasma samples. Linear
      calibration curves were obtained over the range of 0.25-50MUg/mL in plasma for
      both enantiomers (R(2)>0.9990) with quantitation limit of 0.25MUg/mL. The mean
      extraction recoveries were 82.37-91.38% for pioglitazone enantiomers and 95.76%
      for I.S. from rat plasma. The mean relative error (R.E. %) of accuracy and the
      mean relative standard deviation (R.S.D. %) of intra-day and inter-day precision
      for both enantiomers were <10%. The method was validated with accuracy,
      precision, recovery and stability and used to determine the pharmacokinetics of
      pioglitazone enantiomers, after a single oral administration of racemic
      pioglitazone (30mg/kg). The differences between the pharmacokinetic parameters
      Cmax, AUC0-24, AUC0-infinity, CL/F of (+)-pioglitazone and (-)-pioglitazone were
      significant, suggesting that the disposition of pioglitazone in rats may be
      enantioselective. Moreover, the plasma levels of (+)- and (-)-pioglitazone in
      female rats were apparently higher than that in male rats, respectively. 

PMID- 24561311
TI  - The free will inventory: measuring beliefs about agency and responsibility.
AB  - In this paper, we present the results of the construction and validation of a new
      psychometric tool for measuring beliefs about free will and related concepts: The
      Free Will Inventory (FWI). In its final form, FWI is a 29-item instrument with
      two parts. Part 1 consists of three 5-item subscales designed to measure strength
      of belief in free will, determinism, and dualism. Part 2 consists of a series of
      fourteen statements designed to further explore the complex network of people's
      associated beliefs and attitudes about free will, determinism, choice, the soul,
      predictability, responsibility, and punishment. Having presented the construction
      and validation of FWI, we discuss several ways that it could be used in future
      research, highlight some as yet unanswered questions that are ripe for
      interdisciplinary investigation, and encourage researchers to join us in our
      efforts to answer these questions. 

PMID- 24561310
TI  - Antihelminthic niclosamide modulates dendritic cells activation and function.
AB  - Dendritic cells (DCs) link the sensing of the environment by the innate immune
      system to the initiation of adaptive immune responses. Accordingly, DCs are
      considered to be a major target in the development of immunomodulating compounds.
      In this study, the effect of niclosamide, a Food and Drug Administration-approved
      antihelminthic drug, on the activation of lipopolysaccharide (LPS)-stimulated
      murine bone marrow-derived DCs was examined. Our experimental results show that
      niclosamide reduced the pro-inflammatory cytokine and chemokine expression of LPS
      activated DCs. In addition, niclosamide also affected the expression of MHC and
      costimulatory molecules and influenced the ability of the cells to take up
      antigens. Therefore, in mixed cell cultures composed of syngeneic OVA-specific T
      cells and DCs, niclosamide-treated DCs showed a decreased ability to stimulate T
      cell proliferation and IFN-gamma production. Furthermore, intravenous injection
      of niclosamide also attenuated contact hypersensitivity (CHS) in mice during
      sensitization with 2,4-dinitro-1-fluorobenzene. Blocking the LPS-induced
      activation of MAPK-ERK, JNK and NF-kappaB may contribute to the inhibitory effect
      of niclosamide on DC activation. Collectively, our findings suggest that
      niclosamide can manipulate the function of DCs. These results provide new insight
      into the immunopharmacological role of niclosamide and suggest that it may be
      useful for the treatment of chronic inflammatory disorders or DC-mediated
      autoimmune diseases. 

PMID- 24561308
TI  - Effects of cryopreservation on effector cells for antibody dependent cell
      mediated cytotoxicity (ADCC) and natural killer (NK) cell activity in (51)Cr
      release and CD107a assays.
AB  - Freshly isolated PBMC are broadly used as effector cells in functional assays
      that evaluate antibody-dependent cell mediated cytotoxicity (ADCC) and NK
      activity; however, they introduce natural-individual donor-to-donor variability.
      Cryopreserved PBMC provide a more consistent source of effectors than fresh cells
      in cytotoxicity assays. Our objective was to determine the effects of
      cryopreservation of effector PBMC on cell frequency, and on the magnitude and
      specificity of ADCC and NK activity. Fresh, frozen/overnight rested and
      frozen/not rested PBMC were used as effector cells in (51)Cr-release and CD107a
      degranulation assays. Frozen/overnight rested PBMC had higher ADCC and NK
      activity in both assays when compared to fresh PBMC; however, when using
      frozen/not rested PBMC, ADCC and NK activities were significantly lower than
      fresh PBMC. Background CD107a degranulation in the absence of target cell
      stimulation was greater in PBMC that were frozen/not rested when compared to
      fresh PBMC or PBMC that were frozen overnight and rested. The percentages of
      CD16(+)CD56(dim) NK cells and CD14(+) monocytes were lower in PBMC that were
      frozen and rested overnight than in fresh PBMC. CD16 expression on CD56(dim) NK
      cells was similar for all PBMC treatments. PBMC that were frozen and rested
      overnight were comparable to fresh PBMC effectors. PBMC that were frozen and used
      immediately when evaluating ADCC or NK activity using either a (51)Cr-release
      assay or a CD107a degranulation assay had the lowest activity. Clinical studies
      of antibodies that mediate ADCC would benefit from using effector cells that have
      been frozen, thawed and rested overnight prior to assay. 

PMID- 24561312
TI  - Being watched: the effect of social self-focus on interoceptive and exteroceptive
      somatosensory perception.
AB  - We become aware of our bodies interoceptively, by processing signals arising from
      within the body, and exteroceptively, by processing signals arising on or outside
      the body. Recent research highlights the importance of the interaction of
      exteroceptive and interoceptive signals in modulating bodily self-consciousness.
      The current study investigated the effect of social self-focus, manipulated via a
      video camera that was facing the participants and that was either switched on or
      off, on interoceptive sensitivity (using a heartbeat perception task) and on
      tactile perception (using the Somatic Signal Detection Task (SSDT)). The results
      indicated a significant effect of self-focus on SSDT performance, but not on
      interoception. SSDT performance was not moderated by interoceptive sensitivity,
      although interoceptive sensitivity scores were positively correlated with false
      alarms, independently of self-focus. Together with previous research, our results
      suggest that self-focus may exert different effects on body perception depending
      on its mode (private versus social). While interoception has been previously
      shown to be enhanced by private self-focus, the current study failed to find an
      effect of social self-focus on interoceptive sensitivity, instead demonstrating
      that social self-focus improves exteroceptive somatosensory processing. 

PMID- 24561313
TI  - Flavocoxid, dual inhibitor of cyclooxygenase-2 and 5-lipoxygenase, exhibits
      neuroprotection in rat model of ischaemic stroke.
AB  - The efficacy of flavocoxid, a prescription medical food used in osteoarthritis in
      the USA, containing natural flavonoids, baicalin and catechin in experimentally
      induced cerebral ischaemia in rats was evaluated. Rationale behind the study was
      that the transient acute ischaemic attack triggers neuroinflammatory cascade.
      Global cerebral ischaemia was induced transiently by occluding both common
      carotid arteries for 15 min followed by restoration of perfusion. Flavocoxid (50,
      100, 200mg/kg; p.o.) pre-treatment was instituted 6 days prior to surgery and
      fluoxetine (10mg/kg, p.o.) and rivastigmine (2mg/kg, p.o.) as a standard
      treatment for depression and cognition impairment was implied from day 1 after
      the surgery. Different behavioural, biochemical, neurochemical tests, molecular
      markers of inflammation e.g. tumour necrosis factor-alpha, interleukin-1 beta,
      and nuclear factor-kappa B levels and infarct volume were determined.
      Flavocoxid's strong antioxidant properties figured out from the decreased level
      of lipid peroxidation and protection of endogenous antioxidants like reduced
      glutathione and superoxide dismutase. It also reduced TNF-alpha, IL-1beta, and NF
      kappaB levels, and infarct volume as well as protected the loss of biogenic
      amines in brain tissue of ischaemic rats. This dual inhibitor of cyclooxygenase-1
      and 2 with additional 5-lipoxygenase inhibition activity might be useful as a
      potential neuroprotectant medical food in ischaemic stroke prone patient
      population.

PMID- 24561314
TI  - Time-resolved measurement of the three-dimensional motion of gold nanocrystals in
      water using diffracted electron tracking.
AB  - We introduce diffracted electron tracking (DET), which combines two electron
      microscopy techniques, electron backscatter diffraction and the use of an
      environmental cell in a scanning electron microscope to measure changes in
      nanocrystal-orientation. The accuracy of DET was verified by measuring the motion
      of a flat gold crystal caused by the rotation or tilting of the specimen stage.
      DET was applied to measure the motion of semi-fixed gold nanocrystals in various
      environments. In addition to large motions induced in water environment, DET
      could detect small differences in the three-dimensional (3D) motion amplitude
      between vacuum environment and an Ar gas environment. DET promises to be a useful
      method for measuring the motion of single nanocrystals in various environments.
      This measuring technique may be used in a wide range of scientific fields; for
      example, DET may be a prospective method to track the single molecule dynamics of
      molecules labeled with gold nanocrystals. 

PMID- 24561315
TI  - Canine bone marrow stromal cells promote functional recovery in mice with spinal
      cord injury.
AB  - Regenerative therapy has begun to be clinically applied in humans and dogs to
      treat neurological disorders, such as spinal cord injury (SCI). Here, we show the
      therapeutic potential of transplantation of cultured canine bone marrow stromal
      cells (BMSCs) into mice with SCI. Canine BMSC transplantation therapy was
      performed, immediately after the spinal cord was injured. Canine BMSC therapy
      enhanced functional recovery of the hind limbs in mice with SCI. Nestin-positive
      cells were observed only in the lesion of mice with SCI that received BMSCs.
      These results suggest that canine BMSCs promote functional recovery in mice with
      SCI and that migration of nestin-positive cells may contribute to the efficacy of
      the BMSC treatment. 

PMID- 24561316
TI  - Remote and rapid pathological diagnosis in a resource challenged unit.
AB  - Malawi is one of the world's poorest countries, but despite this, has a dedicated
      paediatric oncology service. The service has been hampered by the inability to
      make a timely cytological diagnosis in the majority of patients. A telemedicine
      programme was commenced to help overcome this problem, and the results for the
      first 197 consecutive patients are described. The results are compared with the
      local reports where available. Most samples were fine needle aspirates (104/197
      53%), but others included bone marrow aspirates, peripheral blood films and other
      fluid collections. A diagnosis was arrived at in 52% of the samples; there were
      46 discordant results, 38 were when one or other of the local or distant teams
      were unable to make a diagnosis, and only 8 where the diagnoses of the 2 teams
      differed. Diagnoses were made and reports were compiled by the 'distant' team
      within 24 h and sent to the centre in Malawi. This simple telepathology
      initiative has had a positive impact on clinical management, and could be used in
      other less resourced centres twinned with better resourced ones. 

PMID- 24561317
TI  - Pathology of serrated colorectal lesions.
AB  - The concept of serrated colorectal neoplasia has become recognised as a key
      process in the development of colorectal cancer (CRC) and an important
      alternative pathway to malignancy compared with the long established 'adenoma
      carcinoma' sequence. Increasing recognition of the morphological spectrum of
      serrated lesions has occurred in parallel with elucidation of the distinct
      molecular genetic characteristics of progression from normal mucosa, via the
      'serrated pathway', to CRC. Some of these lesions can be difficult to identify at
      colonoscopy. Challenges for pathologists include the requirement for accurate
      recognition of the forms of serrated lesions that are associated with a
      significant risk of malignant progression and therefore the need for widely
      disseminated reproducible criteria for their diagnosis. Alongside this process,
      pathologists and endoscopists need to formulate clear guidelines for the
      management of patients with these lesions, particularly with respect to the
      optimal follow-up intervals. This review provides practical guidance for the
      recognition of these lesions by pathologists, a discussion of 'serrated
      adenocarcinoma' and an insight into the distinct molecular genetic alterations
      that are seen in this spectrum of lesions in comparison to those that
      characterise the classic 'adenoma-carcinoma' sequence.

PMID- 24561319
TI  - When it hurts to ask: avoiding moral injury in requests to forgo treatment.

PMID- 24561318
TI  - The relationship of attitudinal beliefs to negative symptoms, neurocognition, and
      daily functioning in recent-onset schizophrenia.
AB  - BACKGROUND: In the early course of schizophrenia, premorbid functioning, negative
      symptoms, and neurocognition have been robustly associated with several domains
      of daily functioning. Research with chronic schizophrenia patients suggests that
      attitudinal beliefs may influence daily functioning. However, these relationships
      have not been examined in recent-onset schizophrenia patients. METHODS: The
      sample consisted of recent-onset schizophrenia outpatients (n = 71) who were on
      average 21.7 (SD = 3.3) years old, had 12.5 (SD = 1.8) years of education, and
      5.9 (SD = 6.3) months since psychosis onset. Patients were assessed for premorbid
      adjustment, positive and negative symptoms, neurocognition, attitudinal beliefs,
      and daily functioning. Normal controls (n = 20) were screened for psychopathology
      and demographically matched to the patients. RESULTS: Comparisons indicated that
      recent-onset patients had higher levels of dysfunctional attitudes and lower self
      efficacy compared to healthy controls (t = 3.35, P < .01; t = -4.1, P < .01,
      respectively). Dysfunctional attitudes (r = -.34) and self-efficacy (r = .36)
      were significantly correlated with daily functioning. Negative symptoms were
      found to mediate the relationship between self-efficacy and daily functioning
      (Sobel test, P < .01), as well as between dysfunctional attitudes and daily
      functioning (Sobel test, P < .05). Neurocognition was a significant mediator of
      the relationship between self-efficacy and daily functioning (Sobel test, P <
      .05). DISCUSSION: Early course schizophrenia patients have significantly more
      dysfunctional attitudes and lower self-efficacy than healthy subjects. Both self
      efficacy and dysfunctional attitudes partially contribute to negative symptoms,
      which in turn influence daily functioning. In addition, self-efficacy partially
      contributes to neurocognition, which in turn influences daily functioning.

PMID- 24561320
TI  - Customized device for pediatric upper limb rehabilitation in obstetric brachial
      palsy.
AB  - A 12-yr-old child, with a history of gestational Erb-Duchenne palsy and, later,
      musculoskeletal injuries in the left arm caused by a car accident, inspired the
      design of a customized exoskeleton-like device. Such piece, intended for
      rehabilitation, has one degree of freedom because the exercise routine involves
      elbow flexion-extension, which was indicated for the damaged muscular group. The
      device has two functioning modes, passive and assisted, in which the patient can
      trigger the movement by a biceps contraction, thus promoting the active role of
      the user in the rehabilitation process. The results were evaluated in terms of
      qualitative measures of the biceps and the triceps performed by the medical staff
      and by a questionnaire related to functional activities of the upper limb. A
      significant improvement in the arm movement and elbow angle was observed after 3
      mos of assisted therapy, complementary to conventional exercises. In conclusion,
      a simple and low-cost device was designed and tested to complement the
      rehabilitation process of a pediatric patient with physical impairment. 

PMID- 24561321
TI  - Vertebral sarcoidosis masquerading as breast metastasis.

PMID- 24561322
TI  - Heavy metals in surface sediments of the Jialu River, China: their relations to
      environmental factors.
AB  - This work investigated heavy metal pollution in surface sediments of the Jialu
      River, China. Sediment samples were collected at 19 sites along the river in
      connection with field surveys and the total concentrations were determined using
      atomic fluorescence spectrometer and inductively coupled plasma optical emission
      spectrometer. Sediment samples with higher metal concentrations were collected
      from the upper reach of the river, while sediments in the middle and lower
      reaches had relatively lower metal concentrations. Multivariate techniques
      including Pearson correlation, hierarchical cluster and principal components
      analysis were used to evaluate the metal sources. The ecological risk associated
      with the heavy metals in sediments was rated as moderate based on the assessments
      using methods of consensus-based Sediment Quality Guidelines, Potential
      Ecological Risk Index and Geo-accumulation Index. The relations between heavy
      metals and various environmental factors (i.e., chemical properties of sediments,
      water quality indices and aquatic organism indices) were also studied. Nitrate
      nitrogen, total nitrogen, and total polycyclic aromatic hydrocarbons
      concentrations in sediments showed a co-release behavior with heavy metals.
      Ammonia nitrogen, total nitrogen, orthophosphate, total phosphate and
      permanganate index in water were found to be related to metal sedimentation.
      Heavy metals in sediments posed a potential impact on the benthos community.

PMID- 24561323
TI  - Effect of ZnO nanoparticles aggregation on the toxicity in RAW 264.7 murine
      macrophage.
AB  - Nanostructured zinc oxide (ZnO) has received much attention due to its biological
      and medical applications, where detailed knowledge about particle sizing,
      aggregation propensity and its related hazards are crucial. Herein, the
      aggregation propensity and dissolution behavior of ZnO nanoparticles in aqueous
      medium (PBS) were studied as a function of concentration and further correlated
      with its toxicity in RAW 264.7 murine macrophages. Fast formation of smaller
      aggregates having high dissolution rate was observed at low concentration ZnO (LC
      ZnO). Compared to high concentration ZnO (HC-ZnO) aggregates, the LC-ZnO
      aggregates were highly pronounced in terms of reactive oxygen species generation
      and exerting cell apoptosis, ascribed to the secondary size effect, size
      dependent cellular uptake and ion solubility. This study outlines the
      nanoparticle concentration as a key factor in scaling its aggregation,
      dissolution tendency and also emphasizes the accounting of ingested nanomaterials
      long-term fate inside the cells. 

PMID- 24561324
TI  - The role of gender and sex hormones in determining the onset and outcome of
      multiple sclerosis.
AB  - Intriguing sex differences both in multiple sclerosis (MS) susceptibility and its
      disease course may offer important insights into MS disease pathophysiology,
      prevention and treatment. In this review, we first summarize the key sex-related
      differences in MS risk, heritability and disease progression. One promising
      hypothesis we explore is whether sexually-dimorphic responsiveness to cultural
      and environmental changes may explain the observation of an increasing
      female:male sex ratio in MS. We then review the evidence for hormonal modulation
      of MS, during such transitions as puberty and pregnancy. Finally, we review sex
      differences in the non-inflammatory facets of MS. We highlight those research
      gaps that may point to important sex or sex hormone-mediated mechanistic and
      therapeutic insights.

PMID- 24561325
TI  - Effect of Beauveria bassiana infection on detoxification enzyme transcription in
      pyrethroid resistant Anopheles arabiensis: a preliminary study.
AB  - BACKGROUND: Fungal biopesticides are of great interest to vector control
      scientists as they provide a novel and environmentally friendly alternative to
      insecticide use. The aim of this study was to determine whether genes associated
      with pyrethroid resistance in Anopheles arabiensis from Sudan and South Africa
      are further induced following exposure to the entomopathogenic fungus, Beauveria
      bassiana (strain GHA). METHODS: Following B. bassiana bioassays, RNA was
      extracted from infected mosquitoes and the transcription of four important
      insecticide resistance genes, CYP9L1, CYP6M2 and CYP4G16 (cytochrome P450s) and
      TPX4 (thioredoxin peroxidase) was investigated using quantitative real-time PCR.
      RESULTS: Beauveria bassiana strain GHA was highly infective and virulent against
      An. arabiensis. In terms of changes in gene transcription, overall, the fold
      change (FC) values for each gene in the infected strains, were lower than 1.5.
      The FC values of CYP9L1, CYP6M2 and TPX4, were significantly lower than the FC
      values of the same genes in uninfected resistant An. arabiensis. CONCLUSION:
      These data suggest that B. bassiana does not enhance the pyrethroid resistant
      phenotype on a molecular level as the two An. arabiensis strains used here, with
      different pyrethroid resistance mechanisms, revealed no increase in pre-existing
      metabolic transcripts. This supports the fact that fungal pathogens are suitable
      candidates for vector control, particularly with regard to the development of
      novel vector control strategies.

PMID- 24561326
TI  - Are there meaningful biomarkers of treatment response for depression?
AB  - During the past decades, the prevalence of affective disorders has been on the
      rise globally, with only one out of three patients achieving remission in acute
      treatment with antidepressants. The identification of physiological markers that
      predict treatment course proves useful in increasing therapeutic success. On the
      basis of well-documented, recent findings in depression research, we highlight
      and discuss the most promising biomarkers for antidepressant therapy response.
      These include genetic variants and gene expression profiles, proteomic and
      metabolomic markers, neuroendocrine function tests, electrophysiology and imaging
      techniques. Ultimately, this review proposes an integrative use of biomarkers for
      antidepressant treatment outcome. 

PMID- 24561327
TI  - Learning from 'big data': compounds and targets.

PMID- 24561328
TI  - Hepatotoxicity related to agomelatine and other new antidepressants: a
      case/noncase approach with information from the Portuguese, French, Spanish, and
      Italian pharmacovigilance systems.
AB  - Antidepressants have been associated with a low incidence of idiosyncratic
      hepatic injury. Some of them, nefazodone or amineptine, were observed to induce
      severe hepatic injury and withdrawn from the market. Recently, some cases of this
      severe condition have been reported in association with agomelatine use.
      Therefore, the objective of this study is to learn the risk of hepatic damage
      with agomelatine as compared with other new antidepressants. We took data from
      the Spanish, French, Italian, and Portuguese pharmacovigilance system databases.
      A case/noncase approach to assess the strength of the association between
      whichever antidepressant and hepatotoxicity was performed; cases were defined as
      reports of hepatotoxicity; noncases were reports of all reactions other than
      hepatotoxicity. Exposure was the recording of a new antidepressant in a report,
      whether or not it was suspected of causing the reaction. During the period
      surveyed, 3300 cases of hepatotoxicity were collected for the antidepressants
      assessed. They represent 10.3% of all cases collected for these drugs; the
      corresponding figure for all drugs was 6.0%. Meanwhile, 63 cases of
      hepatotoxicity associated with agomelatine were collected since its introduction
      until the end of the period studied; they account for a percentage of 14.6.
      Agomelatine was statistically associated with hepatotoxicity in Spain [reporting
      odds ratio (ROR), 4.9 (95% confidence interval [CI], 2.4-9.7)], France (ROR, 2.4
      [95% CI, 1.5-3.7]), and Italy (ROR, 5.1 [95% CI, 1.7-14.0]). Current results
      support the idea of agomelatine to be related to a higher hepatotoxicity risk.
      Physicians should consider early discontinuation if the condition is suspected;
      health authorities should promptly explore the best regulatory actions to be
      taken. 

PMID- 24561329
TI  - The accuracy, precision and sustainability of different techniques for tablet
      subdivision: breaking by hand and the use of tablet splitters or a kitchen knife.
AB  - INTRODUCTION: Tablets are frequently subdivided to lower the dose, to facilitate
      swallowing by e.g. children or older people or to save costs. Splitting devices
      are commonly used when hand breaking is difficult or painful. METHODS: Three
      techniques for tablet subdivision were investigated: hand breaking, tablet
      splitter, kitchen knife. A best case drug (paracetamol), tablet (round, flat,
      uncoated, 500 mg) and operator (24-year student) were applied. Hundred tablets
      were subdivided by hand and by three devices of each of the following types: Fit
      & Healthy, Health Care Logistics, Lifetime, PillAid, PillTool, Pilomat tablet
      splitter; Blokker kitchen knife. The intra and inter device accuracy, precision
      and sustainability were investigated. The compliance to (adapted) regulatory
      requirements was investigated also. RESULTS: The accuracy and precision of hand
      broken tablets was 104/97% resp. 2.8/3.2% (one part per tablet considered; parts
      right/left side operator). The right/left accuracies of the splitting devices
      varied between 60 and 133%; the precisions 4.0 and 29.6%. The devices did not
      deteriorate over 100-fold use. Only hand broken tablets complied with all
      regulatory requirements. CONCLUSION: Health care professionals should realize
      that tablet splitting may result in inaccurate dosing. Authorities should
      undertake appropriate measures to assure good function of tablet splitters and,
      where feasible, to reduce the need for their use.

PMID- 24561330
TI  - Synthesis of ?3-2-hydroxybakuchiol analogues and their growth inhibitory activity
      against rat UMR106 cells.
AB  - A series of ?3-2-hydroxybakuchiol analogues have been synthesized and tested for
      their growth inhibitory activity against rat UMR106 cells by using the MTT
      method. Some of them exhibit enhanced activities compared with the natural
      product, and the preliminary SAR profile shows that the chain tail on the natural
      product could be subtly modified to enhance the activity and the aromatic moiety
      or the terminal olefin on the main chain can also be modified without any evident
      loss of activity. The stereo-configuration of the quaternary chiral center has an
      important influence on the activity. 

PMID- 24561331
TI  - Structure and antioxidant activity relationships of isoflavonoids from Dalbergia
      parviflora.
AB  - The antioxidant activities of 24 isoflavonoids that were previously isolated as
      pure compounds from Dalbergia parviflora were evaluated using three different in
      vitro antioxidant-based assay systems: xanthine/xanthine oxidase (X/XO), ORAC,
      and DPPH. The isolates consisted of three subgroups, namely isoflavones,
      isoflavanones, and isoflavans, each of which appeared to have diversified
      substituents, and were thus ideal for the study of their structure-activity
      relationships (SARs). The SAR analysis was performed using the results obtained
      from both the inter-subgroup isoflavonoids with the same substitution pattern and
      the intra-subgroup compounds with different substitution patterns. The inter
      subgroup comparison showed that the isoflavones exhibited the highest antioxidant
      activities based on all three assays. The intra-subgroup analysis showed that the
      additional presence of an OH group in Ring B at either R3' or R5' from the basic
      common structure of the R7-OH of Ring A and the R4'-OH (or -OMe) of Ring B
      greatly increased the antioxidant activities of all of the isoflavonoid subgroups
      and that other positions of OH and OMe substitutions exerted different effects on
      the activities depending on the subgroup and assay type. Therefore, based on the
      structural diversity of the isoflavonoids in D. parviflora, the present study
      provides the first clarification of the detailed antioxidant SARs of
      isoflavonoids. 

PMID- 24561332
TI  - A procedure for implanting organized arrays of microwires for single-unit
      recordings in awake, behaving animals.
AB  - In vivo electrophysiological recordings in the awake, behaving animal provide a
      powerful method for understanding neural signaling at the single-cell level. The
      technique allows experimenters to examine temporally and regionally specific
      firing patterns in order to correlate recorded action potentials with ongoing
      behavior. Moreover, single-unit recordings can be combined with a plethora of
      other techniques in order to produce comprehensive explanations of neural
      function. In this article, we describe the anesthesia and preparation for
      microwire implantation. Subsequently, we enumerate the necessary equipment and
      surgical steps to accurately insert a microwire array into a target structure.
      Lastly, we briefly describe the equipment used to record from each individual
      electrode in the array. The fixed microwire arrays described are well-suited for
      chronic implantation and allow for longitudinal recordings of neural data in
      almost any behavioral preparation. We discuss tracing electrode tracks to
      triangulate microwire positions as well as ways to combine microwire implantation
      with immunohistochemical techniques in order to increase the anatomical
      specificity of recorded results. 

PMID- 24561333
TI  - Effect of different drying methods on the quality of Angelicae Sinensis Radix
      evaluated through simultaneously determining four types of major bioactive
      components by high performance liquid chromatography photodiode array detector
      and ultra-high performance liquid chromatography quadrupole time-of-flight mass
      spectrometry.
AB  - In the present study, the effect of drying methods on the quality of Angelicae
      Sinensis Radix (DG), was evaluated by newly developed high performance liquid
      chromatography photodiode array detector (HPLC-DAD) and ultra-high performance
      liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC-QTOF
      MS/MS). Ten major bioactive components including two phenolic acids, two hydroxyl
      phthalides, four alkyl phthalides and two phthalide dimers were selected as
      evaluation chemical markers and the newly-established method was qualitatively
      and quantitatively validated. DG slices and whole roots dried in shade, sun
      light, hot air, vacuum, microwave, far infrared ray and combination of microwave
      and far infrared ray as well as the fresh DG samples were determined by the
      established methods. DG slices dried in hot air kept the similar chemical
      composition to that of fresh DG, while DG whole roots dried in vacuum retained
      highest contents of the major components. Coniferyl ferulate and ligustilide
      degraded significantly in DG slices dried by microwave, far infrared ray and
      their combination. The influence of such chemical changes induced by different
      drying methods on the bioactivities of DG warrants further investigation, so that
      the optimal drying method can be obtained for the standardization of DG herb. 

PMID- 24561334
TI  - Simultaneous quantification of trans-resveratrol and its sulfate and glucuronide
      metabolites in rat tissues by stable isotope-dilution UPLC-MS/MS analysis.
AB  - A rapid, sensitive, and selective ultra performance liquid chromatography-tandem
      mass spectrometry (UPLC-MS/MS) in the multiple reaction monitoring (MRM) mode has
      been developed and validated to investigate the distribution of trans-Resveratrol
      (Resv) and its metabolites in rats following intravenous (IV) administration at
      20mg/kg body weight (BW). Resv and Resv metabolites were analyzed in the negative
      electrospray ionization mode and eluted with retention times of about 0.69
      2.22min with a runtime of 7min. Stable deuterium-labeled Resv and its metabolites
      were used as the internal standards to correct for matrix effects and to allow
      for accurate quantification of Resv and its metabolites in a complex biological
      system. The method was validated with respect to linearity, within- and between
      day precision, limit of quantification, recovery, and accuracy for all analytes.
      Upon examination at 0.5, 1, 2, and 4h post-administration, concentrations of Resv
      and its metabolites were the highest in the kidney, followed by plasma;
      specifically, the glucuronidated forms were the most abundant. In the liver and
      the brain, the predominant forms were the sulfated derivatives. In contrast,
      heart tissue contained the highest concentration of unmodified Resv at 0.5h post
      IV administration. The combined use of UPLC-MS/MS and isotope-dilution analysis,
      proved to be accurate and reliable in identifying and quantifying Resv and its
      various metabolites in biological samples at the nanomolar range. This technology
      is potentially applicable for other pharmacokinetic studies. 

PMID- 24561335
TI  - Rapid process development of chromatographic process using direct analysis in
      real time mass spectrometry as a process analytical technology tool.
AB  - The concept of quality by design (QbD) is widely applied in the process
      development of pharmaceuticals. However, the additional cost and time have caused
      some resistance about QbD implementation. To show a possible solution, this work
      proposed a rapid process development method, which used direct analysis in real
      time mass spectrometry (DART-MS) as a process analytical technology (PAT) tool
      for studying the chromatographic process of Ginkgo biloba L., as an example. The
      breakthrough curves were fast determined by DART-MS at-line. A high correlation
      coefficient of 0.9520 was found between the concentrations of ginkgolide A
      determined by DART-MS and HPLC. Based on the PAT tool, the impacts of process
      parameters on the adsorption capacity were discovered rapidly, which showed a
      decreased adsorption capacity with the increase of the flow rate. This work has
      shown the feasibility and advantages of integrating PAT into QbD implementation
      for rapid process development. 

PMID- 24561336
TI  - Water determination in active pharmaceutical ingredients using ionic liquid
      headspace gas chromatography and two different detection protocols.
AB  - A rapid, accurate, precise and versatile analytical method was developed for the
      detection and quantification of water in solid active pharmaceutical ingredients
      (APIs). The headspace gas chromatography (HSGC) method utilized an ionic liquid
      (IL) based open tubular capillary GC column to increase sensitivity and
      ruggedness of this method. ILs are also utilized as the headspace solvent because
      of their low vapor pressure, unique physiochemical properties and high thermal
      stability. This method is not affected by side reactions and solubility problems
      which are common with Karl Fischer Titration (KFT) methods. Nor is it as limited
      as weight loss on drying approaches. The ability to use either/both modern
      thermal conductivity or barrier ion discharge GC detection provides flexibility,
      different dynamic ranges and sensitivity. The developed method also was shown to
      be broadly applicable. 

PMID- 24561337
TI  - Preparation of a stir bar coated with molecularly imprinted polymer and its
      application in analysis of dopamine in urine.
AB  - A molecularly imprinted polymer coated stir bar (MIP-SB) using dopamine as a
      template was fabricated. The adsorptive capacity of the MIP-SB was almost 4 times
      over that of non-imprinted stir bar. The MIP-SB showed good extracting
      selectivity for dopamine when used to adsorb dopamine and its analogs. An
      analytical method to determine dopamine in urine sample was established by
      combining MIP-SB sorptive extraction with HPLC-fluorescence detector. The linear
      range of dopamine concentration was 0.378-18.9ng/ml with correlation coefficient
      of 0.9990, and the limit of quantification was about 0.0945ng/ml (S/N=10). The
      recoveries of dopamine with spiked urine samples at three different levels were
      between 92.3 and 106.9%, and the relative standard deviations were within 13.2%
      (n=3). The method is simple and suitable for the determination of dopamine in
      human urine for clinical application. 

PMID- 24561338
TI  - Simultaneous quantification of ruxolitinib and nilotinib in rat plasma by LC
      MS/MS: application to a pharmacokinetic study.
AB  - Efficacy assessments using a combination of ruxolitinib and nilotinib necessitate
      the development of a high precision analytical method for determination of both
      drugs in plasma. A high performance liquid chromatography-tandem mass
      spectrometry (LC-MS/MS) method was developed for the simultaneous determination
      of ruxolitinib and nilotinib in rat plasma. Extraction of ruxolitinib, nilotinib
      and dasatinib (internal standard; IS) from 50MUl rat plasma was carried out by
      protein precipitation with methanol. Chromatographic separation of analytes was
      performed on YMC pack ODS AM (150mm*4.6mm, 5MUm) column under gradient conditions
      with acetonitrile:2.0mM ammonium acetate buffer as the mobile phase at a flow
      rate of 1ml/min. Precursor ion and product ion transition for both analytes and
      IS were monitored on a triple quadrupole mass spectrometer, operated in the
      selective reaction monitoring with positive ionization mode. Method was validated
      over a concentration range of 0.16-247ng/ml for ruxolitinib and 0.86-219ng/ml for
      nilotinib. Mean extraction recovery for ruxolitinib, nilotinib, and IS of 99.6%,
      97.6% and 90.3% were consistent across low, medium, and high QC levels. Precision
      and accuracy at low, medium and high quality control levels were less than 15%
      across analytes. Bench top, wet, freeze-thaw and long term stability were
      evaluated for both analytes. The analytical method was applied to support a
      pharmacokinetic study of simultaneous estimation of ruxolitinib and nilotinib in
      Wistar rat. Assay reproducibility was demonstrated by re-analysis of 18 incurred
      samples. 

PMID- 24561339
TI  - Metabolomics approach for the discrimination of raw and steamed Gastrodia elata
      using liquid chromatography quadrupole time-of-flight mass spectrometry.
AB  - A liquid chromatography quadrupole time-of-flight mass spectrometry-based
      metabolomics approach was applied to metabolite profiling of Gastrodia elata in
      order to identify raw and steamed G. elata and explore potential biomarkers for
      each processing state. A statistical classification method, significant analysis
      of microarrays, was used to select influential metabolites from the different
      forms. Through metabolite selection, several potential biomarkers were determined
      and assigned by matching mass information with that of reference compounds or by
      comparing it with data in the literature. Furthermore, the developed method was
      cross-checked using two validation procedures. The first validation was performed
      simultaneously with the metabolite profiling of G. elata using all detected
      metabolites, and the second was performed after the metabolite profiling using
      representative standard compounds of G. elata. Overall, this study can be applied
      to quality assurance of G. elata. 

PMID- 24561341
TI  - Association between developmental defects of enamel and dental caries in
      schoolchildren.
AB  - Despite improvement, dental caries is still the main public oral health problem
      worldwide and the major cause of pain, tooth loss and chewing difficulties in
      children and adolescents; and it impacts negatively on oral health-related
      quality of life. A cross-sectional study of a multistage representative sample of
      8-12-year-old Brazilian school children was carried out in order to investigate
      the association between enamel defects and dental caries. Children's mothers
      completed a questionnaire about socio-demographic and behavioural characteristics
      at home. Firth's bias reduced logistic regression models were undertaken to
      assess the association between the main exposure (enamel defects) and caries
      experience. The prevalence of any enamel defect was 64.0%; the prevalence of
      diffuse opacities, demarcated opacities and enamel hypoplasia was 35.0%, 29.5%
      and 3.7%, respectively. The prevalence of dental caries was 32.4%, with mean DMFT
      of 0.6 (SD, 1.2). Dental caries experience was more common among children who had
      enamel hypoplasia in their posterior teeth (OR=2.79; 95% CI: 1.05, 6.51) than
      among those with none. In anterior teeth, there was no association. Enamel
      hypoplasia appears to be an important risk factor for dental caries.

PMID- 24561340
TI  - Longitudinal monitoring of demineralization peripheral to orthodontic brackets
      using cross polarization optical coherence tomography.
AB  - OBJECTIVES: The aim of this study was to test the hypothesis that cross
      polarization optical coherence tomography (CP-OCT) can be used to longitudinally
      monitor demineralization peripheral to orthodontic brackets in an extended
      clinical study. METHODS: A high-speed CP-OCT system was used to acquire 3D
      volumetric images of the area at the base of orthodontic brackets over a period
      of 12 months after placement. The reflectivity was measured at 3-month intervals
      for 12 months to determine if there was increased demineralization. Two teeth
      were monitored on 20 test subjects and the brackets were bonded using two types
      of adhesives. This was a randomized controlled clinical study with a split mouth
      design such that each subject served as his or her own control. On one side, the
      control premolar was bonded with a bonding agent (Adper Scotchbond from 3M ESPE,
      St. Paul, MN) and composite (Transbond XT from 3M Unitek, Monrovia, CA) that
      lacked fluoride. On the other side, the experimental premolar was bonded with a
      fluoride releasing glass ionomer cement (GC Fuji Ortho LC from GC America, Alsip,
      IL). RESULTS: There was a small but significant increase in the calculated lesion
      depth and integrated reflectivity over that depth (DeltaR) for both adhesive
      types (p<0.0001) indicating increasing demineralization with time. There was no
      significant difference in the lesion depth (p=0.22) and DeltaR (p=0.91) between
      the groups with the fluoride releasing glass ionomer cement and the conventional
      composite. CONCLUSIONS: CP-OCT was able to measure a significant increase in
      demineralization (p<0.0001) at the base of orthodontic brackets over a period of
      12 months.

PMID- 24561342
TI  - LIM kinase-2 induces programmed necrotic neuronal death via dysfunction of DRP1
      mediated mitochondrial fission.
AB  - Although the aberrant activation of cell cycle proteins has a critical role in
      neuronal death, effectors or mediators of cyclin D1/cyclin-dependent kinase 4
      (CDK4)-mediated death signal are still unknown. Here, we describe a previously
      unsuspected role of LIM kinase 2 (LIMK2) in programmed necrotic neuronal death.
      Downregulation of p27(Kip1) expression by Rho kinase (ROCK) activation induced
      cyclin D1/CDK4 expression levels in neurons vulnerable to status epilepticus
      (SE). Cyclin D1/CDK4 complex subsequently increased LIMK2 expression independent
      of caspase-3 and receptor interacting protein kinase 1 activity. In turn,
      upregulated LIMK2 impaired dynamic-related protein-1 (DRP1)-mediated
      mitochondrial fission without alterations in cofilin phosphorylation/expression
      and finally resulted in necrotic neuronal death. Inhibition of LIMK2 expression
      and rescue of DRP1 function attenuated this programmed necrotic neuronal death
      induced by SE. Therefore, we suggest that the ROCK-p27(Kip1)-cyclin D1/CDK4-LIMK2
      DRP1-mediated programmed necrosis may be new therapeutic targets for neuronal
      death. 

PMID- 24561345
TI  - A novel class dependent feature selection method for cancer biomarker discovery.
AB  - Identifying key biomarkers for different cancer types can improve diagnosis
      accuracy and treatment. Gene expression data can help differentiate between
      cancer subtypes. However the limitation of having a small number of samples
      versus a larger number of genes represented in a dataset leads to the overfitting
      of classification models. Feature selection methods can help select the most
      distinguishing feature sets for classifying different cancers. A new class
      dependent feature selection approach integrates the F-statistic, Maximum
      Relevance Binary Particle Swarm Optimization (MRBPSO) and Class Dependent Multi
      category Classification (CDMC) system. This feature selection method combines
      filter and wrapper based methods. A set of highly differentially expressed genes
      (features) are pre-selected using the F statistic for each dataset as a filter
      for selecting the most meaningful features. MRBPSO and CDMC function as a wrapper
      to select desirable feature subsets for each class and classify the samples using
      those chosen class-dependent feature subsets. The performance of the proposed
      methods is evaluated on eight real cancer datasets. The results indicate that the
      class-dependent approaches can effectively identify biomarkers related to each
      cancer type and improve classification accuracy compared to class independent
      feature selection methods. 

PMID- 24561344
TI  - Cecal ligation and puncture-induced sepsis as a model to study autophagy in mice.
AB  - Experimental sepsis can be induced in mice using the cecal ligation and puncture
      (CLP) method, which causes polymicrobial sepsis. Here, a protocol is provided to
      induce sepsis of varying severity in mice using the CLP technique. Autophagy is a
      fundamental tissue response to stress and pathogen invasion. Two current
      protocols to assess autophagy in vivo in the context of experimental sepsis are
      also presented here. (I) Transgenic mice expressing green fluorescence protein
      (GFP)-LC3 fusion protein are subjected to CLP. Localized enhancement of GFP
      signal (puncta), as assayed either by immunohistochemical or confocal assays, can
      be used to detect enhanced autophagosome formation and, thus, altered activation
      of the autophagy pathway. (II) Enhanced autophagic vacuole (autophagosome)
      formation per unit tissue area (as a marker of autophagy stimulation) can be
      quantified using electron microscopy. The study of autophagic responses to sepsis
      is a critical component of understanding the mechanisms by which tissues respond
      to infection. Research findings in this area may ultimately contribute towards
      understanding the pathogenesis of sepsis, which represents a major problem in
      critical care medicine. 

PMID- 24561346
TI  - Ensemble classification of colon biopsy images based on information rich hybrid
      features.
AB  - In recent years, classification of colon biopsy images has become an active
      research area. Traditionally, colon cancer is diagnosed using microscopic
      analysis. However, the process is subjective and leads to considerable
      inter/intra observer variation. Therefore, reliable computer-aided colon cancer
      detection techniques are in high demand. In this paper, we propose a colon biopsy
      image classification system, called CBIC, which benefits from discriminatory
      capabilities of information rich hybrid feature spaces, and performance
      enhancement based on ensemble classification methodology. Normal and malignant
      colon biopsy images differ with each other in terms of the color distribution of
      different biological constituents. The colors of different constituents are sharp
      in normal images, whereas the colors diffuse with each other in malignant images.
      In order to exploit this variation, two feature types, namely color components
      based statistical moments (CCSM) and Haralick features have been proposed, which
      are color components based variants of their traditional counterparts. Moreover,
      in normal colon biopsy images, epithelial cells possess sharp and well-defined
      edges. Histogram of oriented gradients (HOG) based features have been employed to
      exploit this information. Different combinations of hybrid features have been
      constructed from HOG, CCSM, and Haralick features. The minimum Redundancy Maximum
      Relevance (mRMR) feature selection method has been employed to select meaningful
      features from individual and hybrid feature sets. Finally, an ensemble classifier
      based on majority voting has been proposed, which classifies colon biopsy images
      using the selected features. Linear, RBF, and sigmoid SVM have been employed as
      base classifiers. The proposed system has been tested on 174 colon biopsy images,
      and improved performance (=98.85%) has been observed compared to previously
      reported studies. Additionally, the use of mRMR method has been justified by
      comparing the performance of CBIC on original and reduced feature sets. 

PMID- 24561347
TI  - Muscle activity detection in electromyograms recorded during periodic movements.
AB  - Muscle coordination during periodic movements is often studied using the average
      envelope of the electromyographic (EMG) signal. We show that this method causes a
      loss of important information, and potentially gives rise to errors in analysis
      of muscle activity coordination. We created four simulated two-channel surface
      EMG signals, in order to compare the results of muscle onset/cessation detection,
      performed on the average EMG envelope and the EMG envelopes in every single
      movement cycle. Our results show that the common method using the average EMG
      envelope is unable to reveal certain important characteristics of the EMG
      signals, while the analysis performed on individual cycles accentuates this
      information. This ability was verified on 16-channel surface EMGs obtained during
      walking and cycling. By detecting muscle activity in individual movement cycles,
      we could observe fine changes in muscle coordination. Moreover, muscles with
      questionable reliability of activity detection were distinguished and highlighted
      in the presented summary figures. In the second part of the paper, our publicly
      available set of MATLAB files for surface EMG signal processing is described. 

PMID- 24561343
TI  - Glycan-dependent binding of galectin-1 to neuropilin-1 promotes axonal
      regeneration after spinal cord injury.
AB  - Following spinal cord injury (SCI), semaphorin 3A (Sema3A) prevents axonal
      regeneration through binding to the neuropilin-1 (NRP-1)/PlexinA4 receptor
      complex. Here, we show that galectin-1 (Gal-1), an endogenous glycan-binding
      protein, selectively bound to the NRP-1/PlexinA4 receptor complex in injured
      neurons through a glycan-dependent mechanism, interrupts the Sema3A pathway and
      contributes to axonal regeneration and locomotor recovery after SCI. Although
      both Gal-1 and its monomeric variant contribute to de-activation of microglia,
      only high concentrations of wild-type Gal-1 (which co-exists in a monomer-dimer
      equilibrium) bind to the NRP-1/PlexinA4 receptor complex and promote axonal
      regeneration. Our results show that Gal-1, mainly in its dimeric form, promotes
      functional recovery of spinal lesions by interfering with inhibitory signals
      triggered by Sema3A binding to NRP-1/PlexinA4 complex, supporting the use of this
      lectin for the treatment of SCI patients. 

PMID- 24561348
TI  - Modelling of long-term and short-term mechanisms of arterial pressure control in
      the cardiovascular system: an object-oriented approach.
AB  - A mathematical model that provides an overall description of both the short- and
      long-term mechanisms of arterial pressure regulation is presented. Short-term
      control is exerted through the baroreceptor reflex while renal elimination plays
      a role in long-term control. Both mechanisms operate in an integrated way over
      the compartmental model of the cardiovascular system. The whole system was
      modelled in MODELICA, which uses a hierarchical object-oriented modelling
      strategy, under the DYMOLA simulation environment. The performance of the
      controlled system was analysed by simulation in light of the existing hypothesis
      and validation tests previously performed with physiological data, demonstrating
      the effectiveness of both regulation mechanisms under physiological and
      pathological conditions. 

PMID- 24561349
TI  - Large eddy simulation of the FDA benchmark nozzle for a Reynolds number of 6500.
AB  - This work investigates the flow in a benchmark nozzle model of an idealized
      medical device proposed by the FDA using computational fluid dynamics (CFD). It
      was in particular shown that a proper modeling of the transitional flow features
      is particularly challenging, leading to large discrepancies and inaccurate
      predictions from the different research groups using Reynolds-averaged Navier
      Stokes (RANS) modeling. In spite of the relatively simple, axisymmetric
      computational geometry, the resulting turbulent flow is fairly complex and non
      axisymmetric, in particular due to the sudden expansion. The resulting flow
      cannot be well predicted with simple modeling approaches. Due to the varying
      diameters and flow velocities encountered in the nozzle, different typical flow
      regions and regimes can be distinguished, from laminar to transitional and to
      weakly turbulent. The purpose of the present work is to re-examine the FDA-CFD
      benchmark nozzle model at a Reynolds number of 6500 using large eddy simulation
      (LES). The LES results are compared with published experimental data obtained by
      Particle Image Velocimetry (PIV) and an excellent agreement can be observed
      considering the temporally averaged flow velocities. Different flow regimes are
      characterized by computing the temporal energy spectra at different locations
      along the main axis. 

PMID- 24561350
TI  - Exploring medical diagnostic performance using interactive, multi-parameter
      sourced receiver operating characteristic scatter plots.
AB  - Determining diagnostic criteria for specific disorders is often a tedious task
      that involves determining optimal diagnostic thresholds for symptoms and
      biomarkers using receiver-operating characteristic (ROC) statistics. To help this
      endeavor, we developed softROC, a user-friendly graphic-based tool that lets
      users visually explore possible ROC tradeoffs. The software requires MATLAB
      installation and an Excel file containing threshold symptoms/biological measures,
      with corresponding gold standard diagnoses for a set of patients. The software
      scans the input file for diagnostic and symptom/biomarkers columns, and populates
      the graphical-user-interface (GUI). Users select symptoms/biomarkers of interest
      using Boolean algebra as potential inputs to create diagnostic criteria outputs.
      The software evaluates subtests across the user-established range of cut-points
      and compares them to a gold standard in order to generate ROC and quality ROC
      scatter plots. These plots can be examined interactively to find optimal cut
      points of interest for a given application (e.g. sensitivity versus specificity
      needs). Split-set validation can also be used to set up criteria and validate
      these in independent samples. Bootstrapping is used to produce confidence
      intervals. Additional statistics and measures are provided, such as the area
      under the ROC curve (AUC). As a testing set, softROC is used to investigate
      nocturnal polysomnogram measures as diagnostic features for narcolepsy. All
      measures can be outputted to a text file for offline analysis. The softROC
      toolbox, with clinical training data and tutorial instruction manual, is provided
      as supplementary material and can be obtained online at
      http://www.stanford.edu/~hyatt4/software/softroc or from the open source
      repository at http://www.github.com/informaton/softroc. 

PMID- 24561351
TI  - Metabonomic study of Wu-tou decoction in adjuvant-induced arthritis rat using
      ultra-performance liquid chromatography coupled with quadrupole time-of-flight
      mass spectrometry.
AB  - A urinary metabonomics method based on the ultra-performance liquid
      chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q
      TOF-MS) had been established to investigate the holistic efficacy of Wu-tou
      decoction (WTD), a traditional Chinese medicine (TCM) formula used to treat
      rheumatoid arthritis (RA), in adjuvant-induced arthritis (AIA) rat model.
      Multivariate statistical approaches, such as principal component analysis (PCA)
      and orthogonal projection to latent structures squares-discriminant analysis
      (OPLS-DA) were used to distinguish healthy control group, AIA model group and WTD
      treated group and find potential biomarkers. There was a clear separation among
      the three groups in PCA model. Sixteen potential biomarkers had been identified
      using OPLS-DA, and 11 of them was considered to be in response to therapeutic
      effects of WTD involved in tryptophan metabolism, phenylalanine metabolism,
      tricarboxylic acid (TCA) cycle, bile acid biosynthesis, steroid hormone
      biosynthesis and valine metabolism. In this study, WTD also showed good anti
      inflammatory and antioxidant activities in vivo, and it could suppress
      histopathological changes of AIA rats. There might be a correlation between these
      results and the regulation of the disturbed metabolites in urine. This study
      demonstrates that metabonomics is a powerful methodology to gain insight in the
      mechanism of TCM formula in therapy. 

PMID- 24561352
TI  - R(-)-O-desmethylangolensin is the main enantiomeric form of daidzein metabolite
      produced by human in vitro and in vivo.
AB  - After ingestion, human intestinal bacteria transform daidzein into
      dihydrodaidzein, which can be further metabolised to O-desmethylangolensin. This
      metabolite, unlike daidzein, has a chiral centre and can therefore occur as two
      distinct enantiomers; however, it is unclear which enantiomer is present in
      humans. The aim of this study was to define in vitro and in vivo the structure of
      O-desmethylangolensin and then to evaluate its pharmacokinetic parameters.
      Daidzein metabolism was preliminarily investigated in anaerobic batch cultures
      inoculated with mixed faecal bacteria from O-desmethylangolensin producer
      volunteers. The transformation was monitored by liquid chromatography-mass
      spectrometry and a chiral column was used to distinguish dihydrodaidzein and O
      desmethylangolensin enantiomers. These were purified, analysed by circular
      dichroism and the results established R(-)-O-desmethylangolensin as the main
      product (enantiomer excess 91%). However, both dihydrodaidzein enantiomers were
      detected. Similar results were obtained by in vivo trials. The in vitro formation
      of O-desmethylangolensin seems to be directly correlated with the number of
      transforming microorganisms. This correlation was found in vivo for tmax but not
      for other pharmacokinetic indexes. The pharmacokinetics of daidzein,
      dihydrodaidzein and O-desmethylangolensin were then evaluated in 11 healthy adult
      O-desmethylangolensin producers after the single administration of soy milk
      containing 100mg daidzein. The conjugated forms of daidzein, dihydrodaidzein and
      O-desmethylangolensin represent more than 90 and 95% of the plasmatic and urinary
      forms, respectively. The Cmax, tmax and half-life of O-desmethylangolensin in
      plasma were 62+/-53nM, 28+/-11 and 15+/-6h, respectively. Relevant inter
      individual variations were observed as indicated by the high standard deviations.

PMID- 24561353
TI  - Biosynthesis of magnetic nanostructures in a foreign organism by transfer of
      bacterial magnetosome gene clusters.
AB  - The synthetic production of monodisperse single magnetic domain nanoparticles at
      ambient temperature is challenging. In nature, magnetosomes--membrane-bound
      magnetic nanocrystals with unprecedented magnetic properties--can be
      biomineralized by magnetotactic bacteria. However, these microbes are difficult
      to handle. Expression of the underlying biosynthetic pathway from these
      fastidious microorganisms within other organisms could therefore greatly expand
      their nanotechnological and biomedical applications. So far, this has been
      hindered by the structural and genetic complexity of the magnetosome organelle
      and insufficient knowledge of the biosynthetic functions involved. Here, we show
      that the ability to biomineralize highly ordered magnetic nanostructures can be
      transferred to a foreign recipient. Expression of a minimal set of genes from the
      magnetotactic bacterium Magnetospirillum gryphiswaldense resulted in magnetosome
      biosynthesis within the photosynthetic model organism Rhodospirillum rubrum. Our
      findings will enable the sustainable production of tailored magnetic
      nanostructures in biotechnologically relevant hosts and represent a step towards
      the endogenous magnetization of various organisms by synthetic biology.

PMID- 24561354
TI  - Electrical detection of charge-current-induced spin polarization due to spin
      momentum locking in Bi2Se3.
AB  - Topological insulators exhibit metallic surface states populated by massless
      Dirac fermions with spin-momentum locking, where the carrier spin lies in-plane,
      locked at right angles to the carrier momentum. Here, we show that a charge
      current produces a net spin polarization via spin-momentum locking in Bi2Se3
      films, and this polarization is directly manifested as a voltage on a
      ferromagnetic contact. This voltage is proportional to the projection of the spin
      polarization onto the contact magnetization, is determined by the direction and
      magnitude of the charge current, scales inversely with Bi2Se3 film thickness, and
      its sign is that expected from spin-momentum locking rather than Rashba effects.
      Similar data are obtained for two different ferromagnetic contacts, demonstrating
      that these behaviours are independent of the details of the ferromagnetic
      contact. These results demonstrate direct electrical access to the topological
      insulators' surface-state spin system and enable utilization of its remarkable
      properties for future technological applications. 

PMID- 24561355
TI  - Prevention of vascular inflammation by nanoparticle targeting of adherent
      neutrophils.
AB  - Inflammatory diseases such as acute lung injury and ischaemic tissue injury are
      caused by the adhesion of a type of white blood cell--polymorphonuclear
      neutrophils--to the lining of the circulatory system or vascular endothelium and
      unchecked neutrophil transmigration. Nanoparticle-mediated targeting of activated
      neutrophils on vascular endothelial cells at the site of injury may be a useful
      means of directly inactivating neutrophil transmigration and hence mitigating
      vascular inflammation. Here, we report a method employing drug-loaded albumin
      nanoparticles, which efficiently deliver drugs into neutrophils adherent to the
      surface of the inflamed endothelium. Using intravital microscopy of tumour
      necrosis factor-alpha-challenged mouse cremaster post-capillary venules, we
      demonstrate that fluorescently tagged albumin nanoparticles are largely
      internalized by neutrophils adherent to the activated endothelium via cell
      surface Fcgamma receptors. Administration of albumin nanoparticles loaded with
      the spleen tyrosine kinase inhibitor, piceatannol, which blocks 'outside-in'
      beta2 integrin signalling in leukocytes, detached the adherent neutrophils and
      elicited their release into the circulation. Thus, internalization of drug-loaded
      albumin nanoparticles into neutrophils inactivates the pro-inflammatory function
      of activated neutrophils, thereby offering a promising approach for treating
      inflammatory diseases resulting from inappropriate neutrophil sequestration and
      activation.

PMID- 24561356
TI  - Multi-resolution 3D visualization of the early stages of cellular uptake of
      peptide-coated nanoparticles.
AB  - A detailed understanding of the cellular uptake process is essential to the
      development of cellular delivery strategies and to the study of viral
      trafficking. However, visualization of the entire process, encompassing the fast
      dynamics (local to the freely diffusing nanoparticle) as well the state of the
      larger-scale cellular environment, remains challenging. Here, we introduce a
      three-dimensional multi-resolution method to capture, in real time, the transient
      events leading to cellular binding and uptake of peptide (HIV1-Tat)-modified
      nanoparticles. Applying this new method to observe the landing of nanoparticles
      on the cellular contour in three dimensions revealed long-range deceleration of
      the delivery particle, possibly due to interactions with cellular receptors.
      Furthermore, by using the nanoparticle as a nanoscale 'dynamics pen', we
      discovered an unexpected correlation between small membrane terrain structures
      and local nanoparticle dynamics. This approach could help to reveal the hidden
      mechanistic steps in a variety of multiscale processes. 

PMID- 24561357
TI  - Nanoparticle biosynthesis: An accommodating host.

PMID- 24561358
TI  - A high-throughput method of hemolymph extraction from adult Drosophila without
      anesthesia.
AB  - A rapid and cost-effective method of sampling hemolymph from the model insect
      Drosophila melanogaster is needed for studies in several fields, including
      ionoregulatory physiology, metabolism, immunology and toxicology. Here, we
      describe the construction and use of a device that uses airflow and pressure to
      manipulate adult flies and extract high-volume hemolymph samples. This method is
      rapid and inexpensive, and does not require cold or CO2 anesthesia at any point
      in the sampling process, thus avoiding the possible confounding effects of these
      treatments on the biochemical properties of the hemolymph sampled. To demonstrate
      one use for this method, we measure active concentrations of Na(+) and K(+) in
      isolated hemolymph droplets from individual adult D. melanogaster using an ion
      selective microelectrode technique. 

PMID- 24561359
TI  - Thermal and physical stresses induce a short-term immune priming effect in
      Galleria mellonella larvae.
AB  - Exposure of larvae of Galleria mellonella larvae to mild physical (i.e. shaking)
      or thermal stress for 24h increased their ability to survive infection with
      Aspergillus fumigatus conidia however larvae stressed in a similar manner but
      incubated for 72h prior to infection showed no elevation in their resistance to
      infection with A. fumigatus. Stressed larvae demonstrated an elevated haemocyte
      density 24h after initiation of the stress event but this declined at 48 and 72h.
      Larval proteins such as apolipophorin, arylophorin and prophenoloxidase
      demonstrated elevated expression at 24h but not at 72h. Larvae maintained at 37
      degrees C showed increased expression of a range of antimicrobial and immune
      related proteins at 24h but these decreased in expression thereafter. The results
      presented here indicate that G. mellonella larvae are capable of altering their
      immune response following exposure to mild thermal or physical stress to mount a
      response capable of counteracting microbial infection which reaches a peak 24h
      after the initiation of the priming event and then declines by 72h. A short-term
      immune priming effect may serve to prevent infection but maintaining an immune
      priming effect for longer periods may be metabolically costly and unnecessary
      while living within the colony of another insect. 

PMID- 24561361
TI  - Evaluation of mutation profiling by matrix-assisted laser desorption ionization
      time-of-flight (MALDI-TOF) mass spectrometry in fine needle aspirations from
      papillary thyroid cancer.

PMID- 24561360
TI  - Predictors of breastfeeding duration among women in Kuwait: results of a
      prospective cohort study.
AB  - The purposes of this paper are to report the prevalence of breastfeeding to six
      months among women in Kuwait and to determine the factors that are associated
      with the duration of breastfeeding. A cohort of 373 women recruited from
      maternity wards in four hospitals in Kuwait city were followed from birth to 26
      weeks postpartum. The association of any and full breastfeeding duration and
      predictor variables were explored using multivariate Cox's proportional hazards
      models. At six months, 39% of all infants were receiving some breast milk and
      only 2% of infants had been fully breastfed to 26 weeks. Women born in other Arab
      countries were less likely to discontinue breastfeeding than women born in
      Kuwait. Other factors positively associated with breastfeeding duration were
      level of maternal education, higher parity, infant being demand fed in hospital
      and a preference for breastfeeding on the part of the infant's father and
      maternal grandmother. The introduction of a pacifier before four weeks of age and
      the mother intending to return to work by six months were negatively associated
      with duration. These findings present a number of opportunities for prolonging
      breastfeeding duration in Kuwait. 

PMID- 24561362
TI  - Sensible use of laboratory testing requires active laboratory involvement.

PMID- 24561363
TI  - Lateralized differences in olfactory function and olfactory bulb volume relate to
      nasal septum deviation.
AB  - One of the most common reasons for partial nasal obstruction is nasal septal
      deviation (NSD). The effect of a partial lateralized nasal obstruction on
      olfactory bulb (OB) volume remains unclear. Thus, the aim of this study was to
      investigate the side differences in olfactory function and OB in patients with
      serious NSD. Sixty-five volunteers were included: 22 patients with serious right
      NSD and 43 patients with left NSD. The patients' mean age was 22 years. All
      participants received volumetric magnetic resonance imaging scans of the entire
      brain and detailed lateralized olfactory tests. The majority of the patients
      exhibited an overall decreased olfactory function (as judged for the better
      nostril: functional anosmia in 3%, hyposmia in 72%, normosmia in 25%), which
      seems to be mostly due to the overall severe changes in nasal anatomy. As
      expected, olfactory function was significantly lower at the narrower side as
      indicated for odor thresholds, odor discrimination, and odor identification (P <=
      0.005). When correlating relative scores and volumes (wider minus narrower side),
      a significantly positive correlation between the relative measures emerged for OB
      volume and odor identification, odor discrimination, and odor thresholds. Our
      study clearly highlights that septal deviation results in decreased olfactory
      function at the narrower side. 

PMID- 24561364
TI  - A new method of surgical navigation for orthognathic surgery: optical tracking
      guided free-hand repositioning of the maxillomandibular complex.
AB  - In bimaxillary orthognathic surgery, the positioning of the maxilla and the
      mandible is typically accomplished via 2-splint technique, which may be the
      sources of several types of inaccuracy. To overcome the limitations of the 2
      splint technique, we developed a new navigation method, which guided the surgeon
      to free-hand reposition the maxillomandibular complex as a whole
      intraoperatively, without the intermediate splint. In this preliminary study, the
      feasibility was demonstrated. Five patients with dental maxillofacial deformities
      were enrolled. Before the surgery, 3-dimensional planning was conducted and
      imported into a navigation system. During the operation, a tracker was connected
      to the osteotomized maxillomandibular complex via a splint. The navigation system
      tracked the movement of the complex and displayed it on the screen in real time
      to guide the surgeon to reposition the complex. The postoperative result was
      compared with the plan by analyzing the measured distances between the maxillary
      landmarks and reference planes, as determined from computed tomography data. The
      mean absolute errors of the maxillary position were clinically acceptable (<1.0
      mm). Preoperative preparation time was reduced to 100 minutes on average. All
      patients were satisfied with the aesthetic results. This navigation method
      without intraoperative image registration provided a feasible means of
      transferring virtual planning to the real orthognathic surgery. The real-time
      position of the maxillomandibular complex was displayed on a monitor to visually
      guide the surgeon to reposition the complex. In this method, the traditional
      model surgery and the intermediate splint were discarded, and the preoperative
      preparation was simplified. 

PMID- 24561365
TI  - A preliminary report on the use of antibiotic-impregnated methyl methacrylate in
      salvage cranioplasty.
AB  - In the setting of recurrent infection and multiple failed reconstruction
      attempts, the choice of the ideal reconstructive material for salvage
      cranioplasty remains a source of controversy in the literature. The purpose of
      this study is to establish the safety and utility of antibiotic-impregnated
      polymethyl methacrylate (PMMA) for salvage cranioplasty.A prospectively
      maintained database of all patients who underwent salvage cranioplasty using
      vancomycin and tobramycin-impregnated methyl methacrylate from January 2011 to
      July 2013 was reviewed. Vancomycin and tobramycin were mixed in PMMA, which was
      then applied to a rigidly fixed titanium mesh for reconstruction. Patients'
      demographics, indications, and outcomes of this technique were evaluated.Nine
      patients (mean age: 47 years) underwent vancomycin and tobramycin-impregnated
      PMMA reconstruction with a mean follow-up of 9.3 months (range 3.5-23 months). On
      average, these patients underwent 4 procedures (range: 1-15), which included
      repeat craniotomy, debridement for infection, and failed reconstructions over the
      course of 3.6 years (range: 7 months to 14 years) before salvage cranioplasty.
      All patients required salvage cranioplasty due to infection, with the most common
      bacteria isolated in culture being Propionibacterium acnes (n = 3),
      multiresistant coagulase-negative Staphylococcus (n = 3), methicillin-resistant
      Staphylococcus aureus (n = 2), and Enterobacter (n = 2). The average size of the
      craniectomy defect was 130 cm(2), and there were no incidences of postoperative
      infection, postoperative complications, or need for revisions.To conclude, in
      short-term follow-up, vancomycin and tobramycin-impregnated PMMA reconstruction
      appears safe and effective in salvage cranioplasty. Our early report represents a
      proof of concept--the true test is whether these short-term successes translate
      to stable long-term results.

PMID- 24561366
TI  - Evaluation of plate-related complications and efficacy in fibula free flap
      mandibular reconstruction.
AB  - AIM: The objective of this study was to evaluate the incidence of plate-related
      complications after vascularized bony reconstruction of the mandible, comparing
      the plate type used. PATIENTS AND METHODS: Between 2004 and December 2012, a
      total of 41 free osteocutaneous fibula flaps have been used in an equal number of
      patients for reconstruction of the mandible, at the Division of Maxillofacial
      surgery, San Giovanni Battista Hospital, University of Turin. Malignant pathology
      was the most common indication for segmental mandibulectomy.Patient outcomes were
      retrospectively evaluated with special attention to plate complications such as
      plate fracture, exposure, infection, and bony nonunion.The types of
      reconstruction plates used were mandible plates 2.0, locking plates 2.0,
      miniplates (<2.0), and locking 2.4 plates. RESULTS: Mandible plates 2.0 were used
      in 14 patients, locking plates 2.0 in 12 patients, and locking 2.4 plates in 4
      patients. The most commonly used plates were miniplates, which were used in 86
      patients.A total of 5 plate complications occurred after 41 procedures in an
      equal number of patients.Two complications occurred in patients receiving 2.0
      mandible plates (2/14). One complication occurred in patients receiving 2.0
      locking plates (1/12). Two complications occurred in patients receiving
      miniplates (2/86). CONCLUSIONS: In our experience, miniplates are not associated
      to a high rate of complications comparing to other plates. The advantage of these
      plates and the low rate of complications make them our first choice for
      mandibular reconstructions.

PMID- 24561367
TI  - Pediatric facial fractures as a result of gunshot injuries: an examination of
      associated injuries and trends in management.
AB  - INTRODUCTION: Facial fractures are relatively uncommon in the pediatric
      population, especially those inflicted as a result of interpersonal violence in
      the form of gunshot injuries. Few studies have examined the unique management of
      such high-energy injuries in the pediatric population. Oftentimes the resultant
      damage to soft tissue and bony structures is so great that it challenges the
      previously accepted standards in the management of pediatric facial fractures.
      This study will examine a level 1 trauma center's experience with these unique
      injuries. METHODS: A retrospective review of all facial fractures occurring in a
      pediatric population (those 18 years of age or younger) as a result of gunshot
      wounds in a level 1 trauma center in an urban environment was performed for the
      years 2000 to 2012. Descriptive information was collected regarding each case as
      well as information regarding concomitant injuries, treatment modalities, and
      selected outcomes. RESULTS: During this time period, there were 3147 facial
      fractures treated at our institution, 353 of which were in pediatric patients. Of
      these, 17 were the results of gunshot wounds. Three patients were excluded due to
      insufficient data, leaving a total of 14 patients. The average age of patients
      was 16.5 (range 14-18); all patients were African-American males. The most common
      fracture was that of the mandible (n = 10), with 2 of those patients exhibiting
      panfacial fractures. The average Glasgow Coma Scale on admission was 13.5 (range
      3-15). Six of the patients were intubated in the emergency department. The most
      common concomitant injury was a skull fracture (n = 3), followed by cervical
      spine fractures (n = 2) and intracranial hemorrhages (n = 2). All patients were
      admitted to the hospital for reasons other than fracture management. Seven
      patients ultimately went to the operating room for fracture management. The
      treatment modalities employed were conservative management with closed techniques
      (n = 11), rigid internal fixation (n = 2), and the use of an external fixator
      device (n = 1). Minimal to no soft-tissue debridement was performed in 10 of the
      14 patients, 2 of which presented between 6 months and 10 years post-injury with
      soft-tissue complications related to retained material. The mean hospital length
      of stay was 8.2 days (range 1-18 days). One patient expired. DISCUSSION:
      Pediatric facial fractures as a result of gunshot wounds represent a unique and
      fortunately rare entity that presents a challenge to all disciplines involved in
      treatment. In our patients, there was a tendency towards conservative management,
      with only 3 patients undergoing some form of fixation and only 7 undergoing some
      form of operative debridement. Concomitant injuries and the high-energy nature of
      gunshot wounds often preclude traditional management with rigid fixation to
      ensure adequate bony healing. However, it is important to adequately debride
      devitalized soft tissue and remove all foreign material to avoid future soft
      tissue-related complications.

PMID- 24561368
TI  - Endoscopic-assisted neck tissue expansion in reconstruction of facial burn
      injuries.
AB  - BACKGROUND: Endoscopic-assisted tissue expansion has been recently used in
      plastic surgery. However, there is limited evidence regarding its efficacy in
      reconstruction of facial burn injuries. AIMS: Our study aimed to evaluate the
      utility of endoscopic-assisted neck tissue expansion in reconstruction of facial
      burn deformities. METHODS: Through a prospective study, 42 consecutive patients
      with facial burn injuries attending a major referral center of plastic and
      reconstructive surgery in Iran underwent reconstruction of facial defects with
      endoscopic-assisted neck tissue expansion. Intraoperative events, expansion
      process, and postoperative outcomes were measured for this group of patients.
      RESULTS: The mean +/- SD injected volume for intraoperative expansion was 66 +/-
      3.7 mL (range, 35-80 mL). The mean +/- SD operative time was 45.6 +/- 3.5
      minutes. Moreover, the mean +/- SD distance between the main access incision and
      the expander pocket was 5.6 +/- 1.2 cm. Time to achieve full expansion ranged
      between 12 and 16 weeks, and the expanded volume at the time of reconstruction
      ranged from 400 to 800 mL. All the patients had less than 24 hours of hospital
      stay after placement of tissue expanders. There were only 2 minor complications
      during the postoperative follow-up including 1 case of seroma and 1 case of
      severe pain, which were treated conservatively. CONCLUSIONS: Endoscopic-assisted
      neck tissue expansion is associated with lower complication rate, shorter
      duration of hospitalization, reduced operative time, earlier initiation of
      expansion, and faster expansion process. It could be a feasible alternative to
      open technique in reconstructing facial burns, allowing smaller incision at port
      site, far placement of tissue expander, and excellent visualization of operation
      site.

PMID- 24561369
TI  - Ocular trauma in patients with maxillofacial fractures.
AB  - PURPOSE: The purpose of this study was to analyze and evaluate ocular injuries in
      patients with maxillofacial fractures. Correlation of the ocular injury and
      patients' age, sex, trauma mechanism, and type of maxillofacial fracture was also
      investigated. MATERIALS AND METHODS: From January 2000 to December 2009, a total
      of 1131 patients with facial fractures were registered. The information and data
      collected and analyzed included the following: age, sex, mechanism of injury,
      type of facial fracture, type of ocular injury, and the relationship between
      ocular injury and facial fracture. RESULTS: Ocular injury (349 injuries) was
      sustained by 209 patients (18.5%), with a male/female ratio of 5.33:1 (176 males
      and 33 females). The age range of the patients associated with ocular trauma was
      3 to 68 years (mean [SD], 32.40 [11.27] y). Patients aged 30 to 39 years showed
      the highest risk for ocular trauma (odds ratio [OR], 1.852; P < 0.001). Children
      showed the lowest risk for ocular injuries (OR, 0.162; P < 0.001). Motor vehicle
      accidents were the most common mechanism of injury (97 patients, 46.4%). Motor
      vehicle accidents also had a 2.243-fold risk for ocular trauma (OR, 2.243; P =
      0.021). Ocular traumas were more prone to occur in patients who sustained
      midfacial fractures (OR, 10.232; P < 0.001), especially the patients with
      multiple midfacial fractures (OR, 12.389; P < 0.001). Fracture of the mandible
      had the lowest risk for ocular injuries (multimandibular fractures: OR, 0.035, P
      < 0.001; single mandibular fracture: OR, 0.151; P < 0.001). CONCLUSIONS: The
      occurrence of ocular injuries was significantly related to sex, age, etiology, as
      well as the pattern and position of the maxillofacial fractures.

PMID- 24561370
TI  - Transient ipsilateral mydriasis during correction of left blowout fracture.
AB  - Mydriasis, either bilateral or unilateral, seldom occurs during reconstruction of
      periorbital fracture. Anisocoria, a unilateral mydriasis, requires more urgent
      assessment than bilateral mydriasis does. Pharmacologic agents, local anesthetic
      infiltration, as well as direct or indirect oculomotor nerve damage are possible
      causes of unilateral mydriasis. Few cases have been reported about intraoperative
      temporary ipsilateral mydriasis during correction of blowout fracture. We have
      experienced an unusual case of anisocoria and report the case with literature
      reviews. 

PMID- 24561371
TI  - Recurrent meningitis and frontal encephalocele as delayed complications of
      craniofacial trauma.
AB  - Frontal sinus back table fractures are seen rarely; also, typical presentation of
      frontal sinus encephalocele as a delayed complication of frontal sinus fracture
      is seen more rarely. We present a case of frontal encephalocele and recurrent
      meningitis as delayed complications of craniofacial trauma. Diagnosis,
      management, and treatment approaches of these complications are discussed. 

PMID- 24561372
TI  - Pneumosinus dilatans: is it more than an aesthetic concern?
AB  - BACKGROUND: Pneumosinus dilatans (PD) is a pathologic condition involving the
      hyperaeration of one or several of the paranasal sinuses that can lead to
      significant deformation of the overlying bone. Although the presenting complaint
      of patients with PD is most commonly aesthetic in nature, the condition has also
      been associated with intracranial tumors and several other serious conditions.
      MATERIALS AND METHODS: A meta-analysis of all available clinical publications on
      the subject of PD was conducted. Patients were categorized on the basis of their
      sinus involvement. Associated conditions were also identified and categorized.
      The resulting data were used to further characterize the condition and describe
      previously unreported associations between PD and other conditions. RESULTS: To
      date, a total of 123 cases of PD have been reported. The frontal sinus was the
      most commonly involved (63%), followed by the sphenoid sinus (24%), maxillary
      sinus (20%), and ethmoid sinus (19%). Of patients with symptomatic PD of the
      frontal sinus, 25% had intracranial pathology (meningioma or arachnoid cyst or
      orbital tumor). Patients with sphenoid PD had an 83% chance of having associated
      diagnosis of visual loss, meningioma, or arachnoid cyst, whereas patients with
      ethmoid PD had 83% chance of having associated diagnosis of exophthalmos, vision
      loss, or arachnoid cyst. CONCLUSIONS: Although the presenting complaint of
      patients with PD is most commonly aesthetic in nature, a significant percentage
      may have an associated diagnosis. Health care providers must be able to recognize
      the condition and carry out the appropriate clinical evaluation to avoid missing
      an associated diagnosis.

PMID- 24561373
TI  - Immediate reconstruction after removal of nasal prosthesis using diced cartilage
      wrapped with temporal fascia.
AB  - Various materials are used for nasal augmentations. Silicone is the most
      prevalent because it is durable and facilitates sculpturing. However, the
      unfortunate patient who presents with complication of the nasal implants and
      wants to remove them is vexed with a significant resultant cosmetic defect if the
      implant is removed. However, the patients who have some troubles after
      augmentation by the implants tend to hate the use of the prosthesis again.
      Ideally, immediate reconstruction would be offered to the patient, sparing
      him/her the deformity left by removal of the implant. We treated 16 patients who
      had undergone immediate nasal reconstruction after removal of foreign body. We
      reconstructed nasal deformity by diced cartilage wrapped with temporal fascia.
      The cartilage harvested from the ear concha was finally diced into 1- to 2-mm
      cubes. A bag was made from deep or superficial temporal fascia, and diced
      cartilage cubes were placed in the bag, which was grafted onto the nasal dorsum.
      This procedure had several advantages including getting natural contouring and
      enough volume and absence of foreign body reaction. It was also soft to the touch
      compared with prosthesis. The fascia could support the thin dorsum skin. The
      nasal augmentation effect of this procedure was comparable with that of
      prosthesis methods. It had lower risks for infection and exposure and provided
      more psychologic comfort. The nasal deformities were successfully reconstructed
      using diced cartilage wrapped with temporal fascia. We believe that this is the
      good method for the immediate nasal reconstruction after the removal of foreign
      body. 

PMID- 24561374
TI  - Piezoelectric osteotomy for distraction osteogenesis of the pediatric mandible.
AB  - BACKGROUND: Distraction osteogenesis of the mandible requires a complete
      osteotomy so that the proximal and distal segments may be separated, thereby
      producing length. One of the main complications of this technique is lingual
      nerve injury due to trauma induced by either the saw or the osteotome. The
      purpose of this article was to suggest the use of piezosurgery in performing near
      complete osteotomy of either the body or ramus of the mandible. METHODS: Surgical
      procedure was performed under general anesthesia, and it lasted approximately 90
      minutes. After the buccal cortex of the mandible was dissected, a piezosurgical
      device was used for the planned osteotomy. The gap created by the device allowed
      visualization of the nerve, thereby permitting completion osteotomy of the
      lingual cortex. The patient did not show any neurological postoperative
      complication. CONCLUSIONS: The use of piezoelectric surgery appears to be a safer
      option in performing distraction osteogenesis of the pediatric mandible. The
      presumed disadvantage of this technique, notably an increased operating time due
      to the lower power cut of the piezoelectric device, was not encountered.

PMID- 24561375
TI  - Treatment of microstomia caused by burn with a nasolabial flap--an ingenious
      approach for tugging and fixation of the oral commissure.
AB  - The objectives of surgical treatment for microstomia due to cicatricial
      contracture after burn are to obtain sufficient oral aperture, while maintaining
      sphincter function of the orbicularis oris muscle, and to secure favorable
      function for eating and conversation in addition to good oral health.The lips of
      the mouth have a free border, and the oral aperture, which has been enlarged by
      the operation, tends to be reduced, because of the actions of the orbicularis
      oris muscle. When the orbicularis oris muscle is resected, putting a priority on
      sufficient oral aperture and prevention of redevelopment of contracture, the
      function of the sphincter is often damaged. With the exception of those cases
      with deep extensive burn that damages a wide area of orbicularis oris muscle, the
      muscle should be preserved as expeditiously as is practical. In such cases,
      however, preventive measures for the redevelopment of microstomia should be
      established. As a postoperative adjuvant therapy, the usefulness of splint
      therapy has been suggested in many reports. However, a splint should be used for
      a long period after the surgery, and in some cases, pain is observed with
      therapy. When a splint is not used for an appropriate period, microstomia may
      redevelop. It would be ideal to take preventive measures against the
      redevelopment of contracture during surgery.We provided treatment with some
      ingenious attempts for the nasolabial flap to a patient with microstomia caused
      by cicatricial contracture after burn. We obtained favorable results with no
      postoperative use of a splint. 

PMID- 24561376
TI  - A modified catheterization procedure to reduce bladder damage when collecting
      urine samples from Holstein cows.
AB  - This study proposed a modified procedure, using a small balloon catheter (SB
      catheter, 45 ml), for reducing bladder damage in cows. Holstein cows and the
      following catheters were prepared: smaller balloon catheter (XSB catheter; 30
      ml), SB catheter and standard balloon catheter (NB catheter; 70 ml, as the
      commonly used, standard size). In experiment 1, each cow was catheterized. The
      occurrence of catheter-associated hematuria (greater than 50 RBC/HPF) was lower
      in the SB catheter group (0.0%, n=7) than in the NB catheter group (71.4%, n=7;
      P<0.05). In experiment 2, general veterinary parameters, urine pH, body
      temperature and blood values in cows were not affected before or after insertion
      of SB catheters (n=6). The incidence of urinary tract infection (UTI) was 3.0%
      per catheterized day (n=22). In experiment 3, feeding profiles, daily excretion
      of urinary nitrogen (P<0.05) and rate from nitrogen intake in urine (P<0.01),
      were higher with use of the SB catheter (n=13) than with the use of the vulva
      urine cup (n=18), indicating that using the SB catheter can provide accurate
      nutritional data. From this study, we concluded that when using an SB catheter,
      the following results occur; reduction in bladder damage without any veterinary
      risks and accuracy in regard to feeding parameters, suggesting this modified
      procedure using an SB catheter is a useful means of daily urine collection. 

PMID- 24561377
TI  - Plasma N-terminal pro B-type natriuretic peptide concentrations in dogs with
      pulmonic stenosis.
AB  - The detailed information between plasma N-terminal pro B-type natriuretic peptide
      (NT-proBNP) concentrations and dogs with pulmonic stenosis (PS) is still unknown.
      The aim of the present study was to investigate the clinical utility of measuring
      plasma NT-proBNP concentrations in dogs with PS and to determine whether plasma
      NT-proBNP concentration could be used to assess disease severity. This
      retrospective study enrolled 30 client-owned, untreated dogs with PS
      (asymptomatic [n=23] and symptomatic [n=7]) and 11 healthy laboratory beagles.
      Results of physical examination, thoracic radiography and echocardiography were
      recorded. Plasma NT-proBNP concentrations were measured using commercial
      laboratories. Compared to the healthy control dogs, cardiothoracic ratio was
      significantly increased in dogs with both asymptomatic and symptomatic PS.
      Similarly, the ratio of the main pulmonary artery to aorta was significantly
      decreased in dogs with both asymptomatic and symptomatic PS. The pulmonic
      pressure gradient in the symptomatic PS dogs was significantly higher than that
      in the asymptomatic PS dogs. Plasma NT-proBNP concentration was significantly
      elevated in the symptomatic PS dogs compared to the healthy control dogs and the
      asymptomatic PS dogs. Furthermore, the Doppler-derived pulmonic pressure gradient
      was significantly correlated with the plasma NT-proBNP concentration (r=0.78,
      r(2)=0.61, P<0.0001). Plasma NT-proBNP concentration >764 pmol/l to identify
      severe PS had a sensitivity of 76.2% and specificity of 81.8%. The plasma NT
      proBNP concentration increased by spontaneous PS, i.e. right-sided pressure
      overload and can be used as an additional method to assess the severity of PS in
      dogs. 

PMID- 24561378
TI  - Dicholesteroyl diselenide: cytotoxicity, genotoxicity and mutagenicity in the
      yeast Saccharomyces cerevisiae and in Chinese hamster lung fibroblasts.
AB  - The organoselenium compound, dicholesteroyl diselenide (DCDS) is a structural
      analogue of diphenyl diselenide (DPDS) and may be considered as a promising
      antioxidant drug in vivo. Nevertheless, little is known about the toxicological
      properties of DCDS. In the present study we evaluated the cytotoxic, genotoxic
      and mutagenic properties of DCDS in Chinese hamster lung fibroblasts (V79) and in
      strains of the yeast Saccharomyces cerevisiae, proficient and deficient in
      several DNA-repair pathways. The results with V79 cells show that DCDS induced
      cytotoxicity, GSH depletion and elevation of lipid peroxidation at lower
      concentrations than did DPDS. DCDS also generated single- and double-strand DNA
      breaks in V79 cells, both in the presence and in the absence of metabolic
      activation, as revealed by alkaline and neutral comet assays. Moreover, the
      induction of oxidative DNA base-damage was demonstrated by means of a modified
      comet assay with formamidopyrimidine-DNA glycosylase and endonuclease III.
      Treatment with DCDS also induced micronucleus formation in V79 cells as well as
      point and frame-shift mutations in a haploid wild-type strain of S. cerevisiae.
      Yeast mutants defective in base excision-repair proteins were the most sensitive
      to DCDS. Pre-incubation with N-acetylcysteine reduced DCDS's oxidative, genotoxic
      and mutagenic effects in yeast and in V79 cells. Our findings indicate that the
      presence of cholesteroyl substituents in DCDS results in elevation of its
      cytotoxic and genotoxic potential compared with that of DPDS in yeast and in V79
      cells. However, due to dose-dependent contrasting behaviour of organoselenium
      compounds and differences in their toxicity in in vitro and in vivo systems,
      further studies are needed in order to establish the non-toxic concentration
      range for treatment in mammals. 

PMID- 24561380
TI  - Elevated frequencies of micronuclei in pregnant women with type 1 diabetes
      mellitus and in their newborns.
AB  - Pregestational diabetes mellitus (type 1 and type 2) affects about 1% of the
      obstetric population. In diabetes, persistent hyperglycemia can be a source of
      DNA damage via overproduction of reactive oxygen species (ROS). Using the
      cytokinesis-block micronucleus (CBMN) test, we measured the frequencies of
      micronuclei (MN) per 1000 binucleated (BN) cells in pregnant women (mothers) with
      type 1 diabetes mellitus (T1DM) and in their newborns. Peripheral blood
      lymphocytes were collected from 17 pregnant women with T1DM and cord-blood
      lymphocytes from their 17 newborns. The control group included 40 pregnant women
      (mothers) without diabetes mellitus (DM) and their 40 newborns. In the group of
      pregnant women with T1DM, the mean number of MN per 1000 BN cells was 2.35 (+/
      1.07), significantly (p<0.001) higher than in the control group of pregnant women
      (0.86+/-0.90). The frequency value in the group of newborns of T1DM mothers was
      1.42 (+/-0.60), significantly (p<0.05) higher than in the corresponding control
      group (0.67+/-0.79). The value in the group of mothers with T1DM was
      significantly (p<0.05) higher than in their newborns. Comparing mothers without
      DM with their newborns, no significant frequency differences were observed. No
      significant correlations were observed between MN frequencies in mothers with
      T1DM and either the frequencies in their newborns, the duration of diabetes, or
      HbA1C levels. Our results indicate that T1DM is accompanied by increased
      frequencies of MN in pregnant women and their newborns. 

PMID- 24561379
TI  - The long-term effects of the herbicide atrazine on the dopaminergic system
      following exposure during pubertal development.
AB  - Atrazine (2-chloro-4-ethylamino-6-isopropylamino-s-triazine) is used worldwide as
      a herbicide, and its presence in the environment has resulted in documented human
      exposure. Atrazine has been shown to cause dopaminergic neurotoxicity. The
      juvenile period is particularly vulnerable to environmental agents, but only few
      studies have investigated the long-term effects of atrazine following exposure
      during the pubertal development. Therefore, we evaluated the effects of a 41-day
      exposure to atrazine on the dopaminergic system in rats. Sprague-Dawley rats were
      treated orally with atrazine at 25 or 50mg/kg bw, daily from postnatal day 22 to
      62. The content of dopamine (DA) was examined in striatum samples by HPLC-FL, and
      the mRNA and protein expression of tyrosine hydroxylase (TH), orphan nuclear
      hormone (Nurr1), dopamine transporter (DAT) and vesicular monoaminetransporter 2
      (VMAT2) were examined in samples of the ventral mid-brain by use of fluorescence
      PCR and Western-blot analysis when the rats reached the age of one year. Exposure
      of juvenile rats to the high dose of atrazine led to reduced levels of DA and
      mRNA of Nurr1 in one-year-old animals. This study shows that the long-term
      adverse effects of atrazine on the dopaminergic system have a special relevance
      after juvenile exposure. 

PMID- 24561381
TI  - Cytotoxic and phytotoxic effects of the main chemical components of spent pot
      liner: a comparative approach.
AB  - Spent pot-liner (SPL) is a hazardous solid waste produced by the aluminum
      industry. Although its composition may vary, fluoride and cyanide salts as well
      as aluminum are predominant components. A seed-germination and root-elongation
      test was performed with Lactuca sativa seeds as a test system. SPL induced
      decrease of seed germination rate and root elongation. The concentration of
      26.5g/L SPL was established from a regression curve as the IC50 (inhibition
      concentration 50%). Through chemical analyses, the concentrations of fluoride,
      cyanide and aluminum in SPL solutions of 26.5g/L (IC50), 39.75g/L (1.5IC50) and
      13.25g/L (0.5IC50) were determined. Further, a cell-cycle test was conducted with
      root tips of L. sativa exposed to these same SPL solutions. All test chemicals
      presented toxic effects on meristematic cells of L. sativa. Aluminum was
      identified as the SPL component mainly responsible for reduction of the mitotic
      index. Chromosomal alterations resulted from the interactions among the three
      main chemical components of SPL, without a clear predominantly responsible agent.
      Induction of condensed nuclei was mainly due to effects of aluminum and fluoride,
      and may serve as an indicator of induced cell death. 

PMID- 24561382
TI  - In vivo antimalarial activities of Enantia polycarpa stem bark against Plasmodium
      berghei berghei in mice.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Enantia polycarpa (PC) Engl. Et Diels
      (Annonaceae) is used in traditional medicine as an antimalarial remedy in
      Southern Nigeria. AIM OF THE STUDY: The antimalarial activities of ethanolic stem
      bark extracts of Enantia polycarpa was studied in vivo, in mice infected with
      Plasmodium berghei berghei. MATERIALS AND METHODS: The ethanolic stem bark
      extract of Enantia polycarpa was administered at doses ranging from 200 to 600
      mg/kg/day to Plasmodium berghei infected mice in both early and established
      models of antiplasmodial studies. RESULTS: The extract of Enantia polycarpa
      exhibited promising antimalarial activity against both early and established
      infections. At a dose of 600 mg/kg the extract achieved a 75.8% and 72%
      chemosuppression of parasitaemia in the study of acute and established
      infections, respectively. The extract also prolonged mean survival time of
      Plasmodium berghei infected mice during the study of established infection. The
      mean survival time of mice administered Enantia polycarpa extract at 600
      mg/kg/day (27 days) was significantly longer than infected/untreated control (12
      days). For the acute toxicity study the extract had an intraperitoneal LD50 of
      186 mg/kg but caused no mortality when administered orally at doses as high as
      2,000 and 4,000 mg/kg. CONCLUSIONS: Collectively, the results indicate that
      Enantia polycarpa is safe when administered orally and possesses promising
      antimalarial activity, thus supporting its use in traditional medicine for the
      treatment of malaria.

PMID- 24561383
TI  - Identification and characterization of potent CYP2D6 inhibitors in lotus leaves.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The herb of lotus (Nelumbo nucifera) leaves is a
      commonly used traditional Chinese herbal medicine that is utilized for the
      treatment of sunstroke, to assuage thirst, and to cure both diarrhea and fever in
      China. Modern pharmacological studies have demonstrated that the herb exhibits
      various pharmacological effects, such as anti-hyperlipidemia, anti-obesity, anti
      oxidant, anti-HIV, anti-microbial, and anti-hypoglycemic activities. Currently,
      the herb is becoming more popular in China as a "tea drink" or as a main
      ingredient of some herbal formulations, which implies that the herb and/or its
      products are now more likely to be concurrently administered with conventional
      medicines for losing body weight and reducing blood lipids. However, its
      potential inhibitory effect on human cytochrome P450 (CYP) has not been
      systemically investigated to date. The present study was performed to assess the
      potential inhibitory effects of lotus leaf alcoholic extract (LAE), its major
      fractions, and its main compounds on five CYP isoenzymes (CYP2C9, CYP2C19,
      CYP2D6, CYP2E1, and CYP3A4) in vitro. MATERIAL AND METHODS: Five probe substrates
      were incubated with human liver microsomes in the presence or absence of the LAE,
      the alkaloid fraction (AF), the flavonoid fraction (FF), or the individual
      aporphine alkaloids, namely, nuciferine (NF), N-nornuciferine (N-NF), and 2
      hydroxy-1-methoxyaporphine (HMA). After the incubation, the relative metabolites
      of the substrates were analyzed using LC-MS/MS. RESULTS: The results showed that
      the LAE strongly inhibited CYP2D6 with an IC50 value of 12.05ug/mL and weakly
      inhibited other isoenzymes. In addition, FF was found to weakly inhibit CYP2D6,
      whereas AF exerted a markedly higher inhibitory effect on CYP2D6 activity with an
      IC50 value of 0.96ug/mL. The three aporphine alkaloids isolated from the AF (NF,
      N-NF, and HMA) significantly inhibited CYP2D6 with IC50 values of 3.78, 3.76, and
      3.15uM, respectively. Their Lineweaver-Burk plots and Dixon plots showed that NF,
      N-NF, and HMA competitively inhibited CYP2D6 activity with Ki values of 1.88,
      2.34, and 1.56uM, respectively. CONCLUSION: The study revealed that the alkaloid
      compounds in lotus leaves exert a potent inhibitory effect on CYP2D6 isoenzyme.
      The possible drug interactions of the leaves and their preparations with
      conventional medicines should thus be taken into account.

PMID- 24561384
TI  - Identification of a novel anti-inflammatory compound, alpha-cubebenoate from
      Schisandra chinensis.
AB  - AIMS OF THE STUDY: Extracts of Schisandra chinensis have been used as an anti
      fatigue and tonic agent. Because chronic fatigue syndrome is related to
      inflammatory and oxidative stress, we assessed whether Schisandra chinensis has
      anti-inflammatory constituents and studied the effect of a novel alpha
      cubebenoate isolated from Schisandra chinensis. MATERIALS AND METHODS: alpha
      Cubebenoate was isolated from an extract of Schisandra chinensis fruits. The
      inductions of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2)
      by lipopolysaccharide (LPS) were quantified by RT-PCR and Western blotting in
      mouse peritoneal macrophages. Nitric oxide (NO) and prostaglandin E2 (PGE2) were
      also measured in the media by Griess reagent and EIA method. A mouse model of LPS
      induced peritonitis was used to test the in vivo efficacy of alpha-cubebenoate.
      RESULTS: alpha-Cubebenoate (5-10MUg/ml) inhibited the inductions of iNOS and COX
      2 in mouse peritoneal macrophages at the mRNA and protein levels. LPS-induced
      productions of NO and PGE2 were inhibited by alpha-cubebenoate (5-10MUg/ml). In
      addition, alpha-cubebenoate inhibited the LPS-induced activation of JNK, but not
      those of ERK and p38 MAPK in mouse peritoneal macrophages. Furthermore, in the
      LPS-induced in vivo peritonitis model, alpha-cubebenoate (1mg/kg) strongly
      inhibited the accumulation of polymorph nuclear lymphocytes in the peritoneal
      cavity. CONCLUSION: alpha-Cubebenoate inhibited LPS-induced expression of iNOS
      and COX-2 in a concentration-dependent manner, thereby suppressing productions of
      NO and PGE2 in vitro in peritoneal macrophages. alpha-Cubebenoate also inhibited
      LPS-induced accumulation of polymorph nuclear lymphocytes in LPS-induced
      peritonitis model in vivo. alpha-Cubebenoate may act as an anti-fatigue
      constituent of Schisandra chinensis through anti-inflammation and could be of
      therapeutic use as a treatment for inflammatory diseases.

PMID- 24561385
TI  - Phospholipid profiles of control and glaucomatous human aqueous humor.
AB  - To compare phospholipid (phosphatidylcholine, phosphatidylserine,
      phosphatidylethanolamine and phosphatidylinositol) profiles of human control and
      glaucomatous aqueous humor (AQH). AQH samples were procured during surgery from
      human POAG and control subjects (n = 15 each). Samples were used following
      institutional review board approved protocols and adhering to the tenets of the
      Declaration of Helsinki. Lipid extraction was performed using a modification of
      the Bligh and Dyer method, protein concentrations were determined using the
      Bradford's method, and select samples were confirmed with Densitometry of PHAST
      gels. Lipids were identified and subjected to ratiometric quantification using a
      TSQ Quantum Access Max triple quadrupole mass spectrometer utilizing precursor
      ion scan (PIS) or neutral ion loss scan (NLS) using appropriate class specific
      lipid standards in a two step quantification process. The comparative profiles of
      phosphatidylcholines, phosphatidylserines, phosphatidylethanolamines and
      phosphatidylinositols between control and glaucomatous AQH showed several species
      common between them. A number of unique lipids in all four phospholipid classes
      were also identified in control eyes that were absent in glaucomatous eyes and
      vice versa. A number of phospholipids were found to be uniquely present in
      control, but absent in glaucomatous AQH and vice versa. Compared with a previous
      study of control and POAG red blood cells, a number of these phospholipids are
      absent locally (AQH).

PMID- 24561386
TI  - Nucleus accumbens-specific interventions in RGS9-2 activity modulate responses to
      morphine.
AB  - Regulator of G protein signalling 9-2 (Rgs9-2) modulates the actions of a wide
      range of CNS-acting drugs by controlling signal transduction of several GPCRs in
      the striatum. RGS9-2 acts via a complex mechanism that involves interactions with
      Galpha subunits, the Gbeta5 protein, and the adaptor protein R7BP. Our recent
      work identified Rgs9-2 complexes in the striatum associated with acute or chronic
      exposures to mu opioid receptor (MOR) agonists. In this study we use several new
      genetic tools that allow manipulations of Rgs9-2 activity in particular brain
      regions of adult mice in order to better understand the mechanism via which this
      protein modulates opiate addiction and analgesia. We used adeno-associated
      viruses (AAVs) to express forms of Rgs9-2 in the dorsal and ventral striatum
      (nucleus accumbens, NAc) in order to examine the influence of this protein in
      morphine actions. Consistent with earlier behavioural findings from constitutive
      Rgs9 knockout mice, we show that Rgs9-2 actions in the NAc modulate morphine
      reward and dependence. Notably, Rgs9-2 in the NAc affects the analgesic actions
      of morphine as well as the development of analgesic tolerance. Using optogenetics
      we demonstrate that activation of Channelrhodopsin2 in Rgs9-2-expressing neurons,
      or in D1 dopamine receptor (Drd1)-enriched medium spiny neurons, accelerates the
      development of morphine tolerance, whereas activation of D2 dopamine receptor
      (Drd2)-enriched neurons does not significantly affect the development of
      tolerance. Together, these data provide new information on the signal
      transduction mechanisms underlying opiate actions in the NAc. 

PMID- 24561388
TI  - Selective preservation of the beat in apperceptive music agnosia: a case study.
AB  - INTRODUCTION: Music perception involves processing of melodic, temporal and
      emotional dimensions that have been found to dissociate in healthy individuals
      and after brain injury. Two components of the temporal dimension have been
      distinguished, namely rhythm and metre. We describe an 18 year old male musician
      'JM' who showed apperceptive music agnosia with selectively preserved metre
      perception, and impaired recognition of sad and peaceful music relative to age
      and music experience matched controls after resection of a right temporoparietal
      tumour. METHOD: Two months post-surgery JM underwent a comprehensive
      neuropsychological evaluation including assessment of his music perception
      abilities using the Montreal Battery for Evaluation of Amusia (MBEA, Peretz,
      Champod, & Hyde, 2003). He also completed several experimental tasks to explore
      his ability to recognise famous songs and melodies, emotions portrayed by music
      and a broader range of environmental sounds. Five age-, gender-, education- and
      musical experienced-matched controls were administered the same experimental
      tasks. RESULTS: JM showed selective preservation of metre perception, with
      impaired performances compared to controls and scoring below the 5% cut-off on
      all MBEA subtests, except for the metric condition. He could identify his
      favourite songs and environmental sounds. He showed impaired recognition of sad
      and peaceful emotions portrayed in music relative to controls but intact ability
      to identify happy and scary music. CONCLUSION: This case study contributes to the
      scarce literature documenting a dissociation between rhythmic and metric
      processing, and the rare observation of selectively preserved metric
      interpretation in the context of apperceptive music agnosia. It supports the
      notion that the anterior portion of the superior temporal gyrus (STG) plays a
      role in metric processing and provides the novel observation that selectively
      preserved metre is sufficient to identify happy and scary, but not sad or
      peaceful emotions portrayed in music.

PMID- 24561389
TI  - Nail injury to the brain obfuscated by a fall from height - homicide or suicide?
      a case report.
AB  - Penetrating head injuries caused by unconventional objects such as a nail
      generate speculation and doubt regarding the manner of infliction. We report a
      case of a 24-year-old woman alleged to have committed suicide by a fall from
      height. Autopsy revealed an unprecedented penetrating intracranial injury caused
      by a nail over the right temporal region, confounding the manner of death. The
      underlying intersecting pattern of fractures determined the chronological
      sequence of events. In this paper, we discuss the manner, incidence and pathology
      of nail injuries to the brain. 

PMID- 24561387
TI  - Quantitative multi-modal MRI of the Hippocampus and cognitive ability in
      community-dwelling older subjects.
AB  - Hippocampal structural integrity is commonly quantified using volumetric
      measurements derived from brain magnetic resonance imaging (MRI). Previously
      reported associations with cognitive decline have not been consistent. We
      investigate hippocampal integrity using quantitative MRI techniques and its
      association with cognitive abilities in older age. Participants from the Lothian
      Birth Cohort 1936 underwent brain MRI at mean age 73 years. Longitudinal
      relaxation time (T1), magnetization transfer ratio (MTR), fractional anisotropy
      (FA) and mean diffusivity (MD) were measured in the hippocampus. General factors
      of fluid-type intelligence (g), cognitive processing speed (speed) and memory
      were obtained at age 73 years, as well as childhood IQ test results at age 11
      years. Amongst 565 older adults, multivariate linear regression showed that,
      after correcting for ICV, gender and age 11 IQ, larger left hippocampal volume
      was significantly associated with better memory ability (beta = .11, p = .003),
      but not with speed or g. Using quantitative MRI and after correcting for multiple
      testing, higher T1 and MD were significantly associated with lower scores of g
      (beta range = -.11 to -.14, p < .001), speed (beta range = -.15 to -.20, p <
      .001) and memory (beta range = -.10 to -.12, p < .001). Higher MTR and FA in the
      hippocampus were also significantly associated with higher scores of g (beta
      range = .17 to .18, p < .0001) and speed (beta range = .10 to .15, p < .0001),
      but not memory. Quantitative multi-modal MRI assessments were more sensitive at
      detecting cognition-hippocampal integrity associations than volumetric
      measurements, resulting in stronger associations between MRI biomarkers and age
      related cognition changes.

PMID- 24561390
TI  - Combined steam and ultrasound treatment of broilers at slaughter: a promising
      intervention to significantly reduce numbers of naturally occurring
      campylobacters on carcasses.
AB  - Steam or hot water decontamination treatment of broiler carcasses is hampered by
      process limitations due to prolonged treatment times and adverse changes to the
      epidermis. In this study, a combination of steam with ultrasound (SonoSteam(r))
      was investigated on naturally contaminated broilers that were processed at
      conventional slaughter speeds of 8,500 birds per hour in a Danish broiler plant.
      Industrial-scale SonoSteam equipment was installed in the evisceration room,
      before the inside/outside carcass washer. The SonoSteam treatment was evaluated
      in two separate trials performed on two different dates. Numbers of naturally
      occurring Campylobacter spp. and TVC were determined from paired samples of skin
      excised from opposite sides of the breast of the same carcass, before and after
      treatments. Sampling was performed at two different points on the line: i) before
      and after the SonoSteam treatment and ii) before the SonoSteam treatment and
      after 80 min of air chilling. A total of 44 carcasses were examined in the two
      trials. Results from the first trial showed that the mean initial Campylobacter
      contamination level of 2.35 log10 CFU was significantly reduced (n=12, p<0.001)
      to 1.40 log10 CFU after treatment. A significant reduction (n=11, p<0.001) was
      also observed with samples analyzed before SonoSteam treatment (2.64 log10 CFU)
      and after air chilling (1.44 log10 CFU). In the second trial, significant
      reductions (n=10, p<0.05) were obtained for carcasses analyzed before (mean level
      of 2.23 log10 CFU) and after the treatment (mean level of 1.36 log10 CFU).
      Significant reductions (n=11, p<0.01) were also found for Campylobacter numbers
      analyzed before the SonoSteam treatment (2.02 log10 CFU) and after the air
      chilling treatment (1.37 log10 CFU). The effect of air chilling without SonoSteam
      treatment was determined using 12 carcasses pre- and postchill. Results showed
      insignificant reductions of 0.09 log10 from a mean initial level of 2.19 log10
      CFU. Numbers of TVC before treatments ranged between 3.47 and 4.79 log10 CFU. In
      all cases, TVC was significantly (p<0.001, n=45 in each trial) reduced by
      approximately 0.7 log10 CFU. An authorized sensory panel at the Danish Veterinary
      and Food Administration concluded that broiler carcasses treated with SonoSteam
      were acceptable for purchase. These conclusions were based on organoleptic
      differences (smell, skin/meat consistency, texture and color) of treated vs.
      untreated carcasses. Results obtained from this study suggest that steam
      ultrasound treatment of carcasses at broiler processing plants can significantly
      reduce numbers of Campylobacter on naturally contaminated broilers.

PMID- 24561391
TI  - Sequence and comparative analysis of Leuconostoc dairy bacteriophages.
AB  - Bacteriophages attacking Leuconostoc species may significantly influence the
      quality of the final product. There is however limited knowledge of this group of
      phages in the literature. We have determined the complete genome sequences of
      nine Leuconostoc bacteriophages virulent to either Leuconostoc mesenteroides or
      Leuconostoc pseudomesenteroides strains. The phages have dsDNA genomes with sizes
      ranging from 25.7 to 28.4 kb. Comparative genomics analysis helped classify the 9
      phages into two classes, which correlates with the host species. High percentage
      of similarity within the classes on both nucleotide and protein levels was
      observed. Genome comparison also revealed very high conservation of the overall
      genomic organization between the classes. The genes were organized in functional
      modules responsible for replication, packaging, head and tail morphogenesis, cell
      lysis and regulation and modification, respectively. No lysogeny modules were
      detected. To our knowledge this report provides the first comparative genomic
      work done on Leuconostoc dairy phages.

PMID- 24561392
TI  - Prepregnancy SHBG concentrations and risk for subsequently developing gestational
      diabetes mellitus.
AB  - OBJECTIVE: Lower levels of sex hormone-binding globulin (SHBG) have been
      associated with increased risk of diabetes among postmenopausal women; however,
      it is unclear whether they are associated with glucose intolerance in younger
      women. We examined whether SHBG concentrations, measured before pregnancy, are
      associated with risk of gestational diabetes mellitus (GDM). RESEARCH DESIGN AND
      METHODS: This was a nested case-control study among women who participated in the
      Kaiser Permanente Northern California Multiphasic Health Check-up examination
      (1984-1996) and had a subsequent pregnancy (1984-2009). Eligible women were free
      of recognized diabetes. Case patients were 256 women in whom GDM developed. Two
      control subjects were selected for each case patient and were matched for year of
      blood draw, age at examination, age at pregnancy, and number of intervening
      pregnancies. RESULTS: Compared with the highest quartile of SHBG concentrations,
      the odds of GDM increased with decreasing quartile (odds ratio 1.06 [95% CI 0.44
      2.52]; 2.33 [1.07-5.09]; 4.06 [1.90-8.65]; P for trend < 0.001), after adjusting
      for family history of diabetes, prepregnancy BMI, race/ethnicity, alcohol use,
      prepregnancy weight changes, and homeostasis model assessment of insulin
      resistance. Having SHBG levels below the median (<64.5 nmol/L) and a BMI >=25.0
      kg/m(2) was associated with fivefold increased odds of GDM compared with normal
      weight women with SHBG levels at or above the median (5.34 [3.00-9.49]).
      CONCLUSIONS: Low prepregnancy SHBG concentrations were associated with increased
      risk of GDM and might be useful in identifying women at risk for GDM for early
      prevention strategies.

PMID- 24561393
TI  - Clinical Pharmacogenetics Implementation Consortium Guidelines for HLA-B Genotype
      and Abacavir Dosing: 2014 update.
AB  - The Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for HLA
      B Genotype and Abacavir Dosing were originally published in April 2012. We
      reviewed recent literature and concluded that none of the evidence would change
      the therapeutic recommendations in the original guideline; therefore, the
      original publication remains clinically current. However, we have updated the
      Supplementary Material online and included additional resources for applying CPIC
      guidelines to the electronic health record. Up-to-date information can be found
      at PharmGKB (http://www.pharmgkb.org). 

PMID- 24561394
TI  - Maternal exposure to biomass smoke and carbon monoxide in relation to adverse
      pregnancy outcome in two high altitude cities of Peru.
AB  - BACKGROUND: Exposure to pollution from biomass fuel has been associated with low
      birthweight in some studies. Few studies have included exposure-response
      analyses. METHOD: We conducted a case-control study of biomass fuel use and
      reproductive outcome at high altitude in Peru. Cases (n=101) were full term
      births who were SGA (birth weight <10th percentile for gestational age). Controls
      (n=101) had a birthweight >=10th percentile, and were matched to cases on birth
      week and residence. Biomass fuel use during pregnancy was determined by
      questionnaire. Carbon monoxide (CO) in the kitchen was measured in a subgroup
      (n=72). Logistic regression was used to estimate the effects of biofuel and CO on
      the risk of SGA, controlling for maternal education and parity. RESULTS: Among
      cases, 30%, 27% and 44% used gas, gas+biomass, and biomass, respectively, while
      the figures for controls were 39%, 33%, and 29%. The adjusted odds ratio (OR) for
      biomass fuel alone compared with gas alone was 4.5 (95% CI: 1.3, 15.5, p=0.02),
      while the OR for biomass+gas vs. gas alone was 2.1 (0.80-5.5) (p=0.13). Among the
      subgroup with measured CO, the mean 48-h kitchen CO levels were 4.8, 2.2 and
      0.4ppm for biofuel only, biofuel+gas, and gas respectively. ORs by increasing
      tertile of CO level were 1.0, 1.16, and 3.53 (test for trend, p=0.02). The
      exposure-response trend corresponds well with one other study with analogous
      data. CONCLUSION: Despite limited sample size, our data suggest that maternal
      exposure to biomass smoke and CO, at high altitude, is associated with SGA among
      term births.

PMID- 24561395
TI  - Measuring material microstructure under flow using 1-2 plane flow-small angle
      neutron scattering.
AB  - A new small-angle neutron scattering (SANS) sample environment optimized for
      studying the microstructure of complex fluids under simple shear flow is
      presented. The SANS shear cell consists of a concentric cylinder Couette geometry
      that is sealed and rotating about a horizontal axis so that the vorticity
      direction of the flow field is aligned with the neutron beam enabling scattering
      from the 1-2 plane of shear (velocity-velocity gradient, respectively). This
      approach is an advance over previous shear cell sample environments as there is a
      strong coupling between the bulk rheology and microstructural features in the 1-2
      plane of shear. Flow-instabilities, such as shear banding, can also be studied by
      spatially resolved measurements. This is accomplished in this sample environment
      by using a narrow aperture for the neutron beam and scanning along the velocity
      gradient direction. Time resolved experiments, such as flow start-ups and large
      amplitude oscillatory shear flow are also possible by synchronization of the
      shear motion and time-resolved detection of scattered neutrons. Representative
      results using the methods outlined here demonstrate the useful nature of spatial
      resolution for measuring the microstructure of a wormlike micelle solution that
      exhibits shear banding, a phenomenon that can only be investigated by resolving
      the structure along the velocity gradient direction. Finally, potential
      improvements to the current design are discussed along with suggestions for
      supplementary experiments as motivation for future experiments on a broad range
      of complex fluids in a variety of shear motions. 

PMID- 24561396
TI  - Leptin and aging.

PMID- 24561398
TI  - A new omni-directional EMAT for ultrasonic Lamb wave tomography imaging of
      metallic plate defects.
AB  - This paper proposes a new omni-directional electromagnetic acoustic transducer
      (EMAT) for the ultrasonic Lamb wave (ULW) tomography imaging (TI) of defects in
      metallic plates. The proposed EMAT is composed of a permanent magnet and a coil
      with a contra-flexure structure. This new EMAT coil structure is used for omni
      directional ULW transmission and reception and ULW TI for the first time. The
      theoretical background and the working principles of this EMAT are presented and
      analyzed. The experimental results of its use on a 3 mm thick aluminum plate
      indicate that the EMAT with a contra-flexure coil (CFC) can transmit and receive
      a pure single A0 mode ULW with a high signal-to-noise ratio (SNR). Thus, the
      extraction of the projection data used for ULW TI may be performed accurately.
      The circumferential consistency of the projection data is only slightly
      influenced by the distortion of the eddy current field that is induced by the new
      CFC with an irregular shape. When the new EMAT array is used for ULW TI using the
      cross-hole method and SIRT arithmetic, a desirable imaging quality can be
      achieved, and the estimated size of an artificial corrosion defect agreed well
      with its actual value. The relation between the reconstruction resolution and the
      number of the new EMATs used is analyzed. More TI experiments are carried out
      when the aluminum plate defect is in two different locations relative to the EMAT
      array, for the further investigation of the performances of the new EMATs. 

PMID- 24561397
TI  - Reliability of gadolinium-enhanced magnetic resonance imaging findings and their
      correlation with clinical outcome in patients with sciatica.
AB  - BACKGROUND CONTEXT: Gadolinium-enhanced magnetic resonance imaging (Gd-MRI) is
      often performed in the evaluation of patients with persistent sciatica after
      lumbar disc surgery. However, correlation between enhancement and clinical
      findings is debated, and limited data are available regarding the reliability of
      enhancement findings. PURPOSE: To evaluate the reliability of Gd-MRI findings and
      their correlation with clinical findings in patients with sciatica. STUDY DESIGN:
      Prospective observational evaluation of patients who were enrolled in a
      randomized trial with 1-year follow-up. PATIENTS SAMPLE: Patients with 6- to 12
      week sciatica, who participated in a multicentre randomized clinical trial
      comparing an early surgery strategy with prolonged conservative care with surgery
      if needed. In total 204 patients underwent Gd-MRI at baseline and after 1 year.
      OUTCOME MEASURES: Patients were assessed by means of the Roland Disability
      Questionnaire (RDQ) for sciatica, visual analog scale (VAS) for leg pain, and
      patient-reported perceived recovery at 1 year. Kappa coefficients were used to
      assess interobserver reliability. METHODS: In total, 204 patients underwent Gd
      MRI at baseline and after 1 year. Magnetic resonance imaging findings were
      correlated to the outcome measures using the Mann-Whitney U test for continuous
      data and Fisher exact tests for categorical data. RESULTS: Poor-to-moderate
      agreement was observed regarding Gd enhancement of the herniated disc and
      compressed nerve root (kappa<0.41), which was in contrast with excellent
      interobserver agreement of the disc level of the herniated disc and compressed
      nerve root (kappa>0.95). Of the 59 patients with an enhancing herniated disc at 1
      year, 86% reported recovery compared with 100% of the 12 patients with
      nonenhancing herniated discs (p=.34). Of the 12 patients with enhancement of the
      most affected nerve root at 1 year, 83% reported recovery compared with 85% of
      the 192 patients with no enhancement (p=.69). Patients with and without enhancing
      herniated discs or nerve roots at 1 year reported comparable outcomes on RDQ and
      VAS-leg pain. CONCLUSIONS: Reliability of Gd-MRI findings was poor-to-moderate
      and no correlation was observed between enhancement and clinical findings at 1
      year follow-up.

PMID- 24561399
TI  - Modeling of the through-the-thickness electric potentials of a piezoelectric
      bimorph using the spectral element method.
AB  - An efficient spectral element (SE) with electric potential degrees of freedom
      (DOF) is proposed to investigate the static electromechanical responses of a
      piezoelectric bimorph for its actuator and sensor functions. A sublayer model
      based on the piecewise linear approximation for the electric potential is used to
      describe the nonlinear distribution of electric potential through the thickness
      of the piezoelectric layers. An equivalent single layer (ESL) model based on
      first-order shear deformation theory (FSDT) is used to describe the displacement
      field. The Legendre orthogonal polynomials of order 5 are used in the element
      interpolation functions. The validity and the capability of the present SE model
      for investigation of global and local responses of the piezoelectric bimorph are
      confirmed by comparing the present solutions with those obtained from coupled 3-D
      finite element (FE) analysis. It is shown that, without introducing any higher
      order electric potential assumptions, the current method can accurately describe
      the distribution of the electric potential across the thickness even for a rather
      thick bimorph. It is revealed that the effect of electric potential is
      significant when the bimorph is used as sensor while the effect is insignificant
      when the bimorph is used as actuator, and therefore, the present study may
      provide a better understanding of the nonlinear induced electric potential for
      bimorph sensor and actuator. 

PMID- 24561400
TI  - RF-to-DC characteristics of direct irradiated on-chip gallium arsenide Schottky
      diode and antenna for application in proximity communication system.
AB  - We report the RF-to-DC characteristics of the integrated AlGaAs/GaAs Schottky
      diode and antenna under the direct injection and irradiation condition. The
      conversion efficiency up to 80% under direct injection of 1 GHz signal to the
      diode was achieved. It was found that the reduction of series resistance and
      parallel connection of diode and load tend to lead to the improvement of RF-to-DC
      conversion efficiency. Under direct irradiation from antenna-to-antenna method,
      the output voltage of 35 mV was still obtainable for the distance of 8 cm between
      both antennas in spite of large mismatch in the resonant frequency between the
      diode and the connected antenna. Higher output voltage in volt range is expected
      to be achievable for the well-matching condition. The proposed on-chip
      AlGaAs/GaAs HEMT Schottky diode and antenna seems to be a promising candidate to
      be used for application in proximity communication system as a wireless low power
      source as well as a highly sensitive RF detector. 

PMID- 24561401
TI  - A survey on sensor coverage and visual data capturing/processing/transmission in
      wireless visual sensor networks.
AB  - Wireless Visual Sensor Networks (WVSNs) where camera-equipped sensor nodes can
      capture, process and transmit image/video information have become an important
      new research area. As compared to the traditional wireless sensor networks (WSNs)
      that can only transmit scalar information (e.g., temperature), the visual data in
      WVSNs enable much wider applications, such as visual security surveillance and
      visual wildlife monitoring. However, as compared to the scalar data in WSNs,
      visual data is much bigger and more complicated so intelligent schemes are
      required to capture/process/ transmit visual data in limited resources (hardware
      capability and bandwidth) WVSNs. WVSNs introduce new multi-disciplinary research
      opportunities of topics that include visual sensor hardware, image and multimedia
      capture and processing, wireless communication and networking. In this paper, we
      survey existing research efforts on the visual sensor hardware, visual sensor
      coverage/deployment, and visual data capture/ processing/transmission issues in
      WVSNs. We conclude that WVSN research is still in an early age and there are
      still many open issues that have not been fully addressed. More new novel multi
      disciplinary, cross-layered, distributed and collaborative solutions should be
      devised to tackle these challenging issues in WVSNs. 

PMID- 24561402
TI  - Characterizing and authenticating Montilla-Moriles PDO vinegars using near
      infrared reflectance spectroscopy (NIRS) technology.
AB  - This study assessed the potential of near infrared (NIR) spectroscopy as a non
      destructive method for characterizing Protected Designation of Origin (PDO)
      "Vinagres de Montilla-Moriles" wine vinegars and for classifying them as a
      function of the manufacturing process used. Three spectrophotometers were
      evaluated for this purpose: two monochromator instruments (Foss NIRSystems 6500
      SY-I and Foss NIRSystems 6500 SY-II; spectral range 400-2,500 nm in both cases)
      and a diode-array instrument (Corona 45 VIS/NIR; spectral range 380-1,700 nm). A
      total of 70 samples were used to predict major chemical quality parameters (total
      acidity, fixed acidity, volatile acidity, pH, dry extract, ash, acetoin,
      methanol, total polyphenols, color (tonality and intensity), and alcohol
      content), and to construct models for the classification of vinegars as a
      function of the manufacturing method used. The results obtained indicate that
      this non-invasive technology can be used successfully by the vinegar industry and
      by PDO regulators for the routine analysis of vinegars in order to authenticate
      them and to detect potential fraud. Slightly better results were achieved with
      the two monochromator instruments. The findings also highlight the potential of
      these NIR instruments for predicting the manufacturing process used, this being
      of particular value for the industrial authentication of traditional wine
      vinegars. 

PMID- 24561404
TI  - A proposed scalable design and simulation of wireless sensor network-based long
      distance water pipeline leakage monitoring system.
AB  - Anomalies such as leakage and bursts in water pipelines have severe consequences
      for the environment and the economy. To ensure the reliability of water
      pipelines, they must be monitored effectively. Wireless Sensor Networks (WSNs)
      have emerged as an effective technology for monitoring critical infrastructure
      such as water, oil and gas pipelines. In this paper, we present a scalable design
      and simulation of a water pipeline leakage monitoring system using Radio
      Frequency IDentification (RFID) and WSN technology. The proposed design targets
      long-distance aboveground water pipelines that have special considerations for
      maintenance, energy consumption and cost. The design is based on deploying a
      group of mobile wireless sensor nodes inside the pipeline and allowing them to
      work cooperatively according to a prescheduled order. Under this mechanism, only
      one node is active at a time, while the other nodes are sleeping. The node whose
      turn is next wakes up according to one of three wakeup techniques: location
      based, time-based and interrupt-driven. In this paper, mathematical models are
      derived for each technique to estimate the corresponding energy consumption and
      memory size requirements. The proposed equations are analyzed and the results are
      validated using simulation. 

PMID- 24561403
TI  - Laccase biosensor based on electrospun copper/carbon composite nanofibers for
      catechol detection.
AB  - The study compared the biosensing properties of laccase biosensors based on
      carbon nanofibers (CNFs) and copper/carbon composite nanofibers (Cu/CNFs). The
      two kinds of nanofibers were prepared by electrospinning and carbonization under
      the same conditions. Scanning electron microscopy (SEM), X-ray diffraction (XRD)
      and Raman spectroscopy were employed to investigate the morphologies and
      structures of CNFs and Cu/CNFs. The amperometric results indicated that the
      Cu/CNFs/laccase(Lac)/Nafion/glass carbon electrode (GCE) possessed reliable
      analytical performance for the detection of catechol. The sensitivity of the
      Cu/CNFs/Lac/Nafion/GCE reached 33.1 MUA/mM, larger than that of
      CNFs/Lac/Nafion/GCE. Meanwhile, Cu/CNFs/Lac/Nafion/GCE had a wider linear range
      from 9.95 * 10(-6) to 9.76 * 10(-3) M and a lower detection limit of 1.18 MUM
      than CNFs/Lac/Nafion/GCE. Moreover, it exhibited a good repeatability,
      reproducibility, selectivity and long-term stability, revealing that electrospun
      Cu/CNFs have great potential in biosensing.

PMID- 24561405
TI  - Investigating energy-saving potentials in the cloud.
AB  - Collecting webpage messages can serve as a sensor for investigating the energy
      saving potential of buildings. Focusing on stores, a cloud sensor system is
      developed to collect data and determine their energy-saving potential. The owner
      of a store under investigation must register online, report the store address,
      area, and the customer ID number on the electric meter. The cloud sensor system
      automatically surveys the energy usage records by connecting to the power company
      website and calculating the energy use index (EUI) of the store. Other data
      includes the chain store check, company capital, location price, and the
      influence of weather conditions on the store; even the exposure frequency of
      store under investigation may impact the energy usage collected online. After
      collecting data from numerous stores, a multi-dimensional data array is
      constructed to determine energy-saving potential by identifying stores with
      similarity conditions. Similarity conditions refer to analyzed results that
      indicate that two stores have similar capital, business scale, weather
      conditions, and exposure frequency on web. Calculating the EUI difference or pure
      technical efficiency of stores, the energy-saving potential is determined. In
      this study, a real case study is performed. An 8-dimensional (8D) data array is
      constructed by surveying web data related to 67 stores. Then, this study
      investigated the savings potential of the 33 stores, using a site visit, and
      employed the cloud sensor system to determine the saving potential. The case
      study results show good agreement between the data obtained by the site visit and
      the cloud investigation, with errors within 4.17%. Among 33 the samples, eight
      stores have low saving potentials of less than 5%. The developed sensor on the
      cloud successfully identifies them as having low saving potential and avoids
      wasting money on the site visit. 

PMID- 24561406
TI  - Conducting polymer-based nanohybrid transducers: a potential route to high
      sensitivity and selectivity sensors.
AB  - The development of novel sensing materials provides good opportunities to realize
      previously unachievable sensor performance. In this review, conducting polymer
      based nanohybrids are highlighted as innovative transducers for high-performance
      chemical and biological sensing devices. Synthetic strategies of the nanohybrids
      are categorized into four groups: (1) impregnation, followed by reduction; (2)
      concurrent redox reactions; (3) electrochemical deposition; (4) seeding approach.
      Nanocale hybridization of conducting polymers with inorganic components can lead
      to improved sorption, catalytic reaction and/or transport behavior of the
      material systems. The nanohybrids have thus been used to detect nerve agents,
      toxic gases, volatile organic compounds, glucose, dopamine, and DNA. Given
      further advances in nanohybrids synthesis, it is expected that sensor technology
      will also evolve, especially in terms of sensitivity and selectivity. 

PMID- 24561407
TI  - Treating rheumatoid arthritis to target: a Canadian patient survey.
AB  - BACKGROUND: Recently, many countries, including Canada, evaluated
      rheumatologists' acceptance and agreement with a set of 10 Treat to Target (T2T)
      recommendations for rheumatoid arthritis (RA), developed by an international task
      force. In this study, the Canadian T2T steering committee evaluated how Canadian
      patients with RA perceive these recommendations. OBJECTIVES: The objectives of
      this study were to assess the current state of RA management in Canada from a
      patient perspective and to assess whether and to what extent Canadians with RA
      agree with each of the 10 T2T recommendations and to compare the results with a
      previous survey completed by physicians. METHODS: Participating rheumatologists
      were asked to invite consecutive RA patients to complete a 20-question survey.
      The survey was designed to assess relevant sociodemographic variables, the
      current treatment, and the approach to RA management as seen from the patient's
      perspective, as well as their agreement with the T2T recommendations. RESULTS: A
      total of 959 patients (77% were female) were recruited by 22 participating
      rheumatologists from 6 Canadian provinces. Patients had a mean age of 59.1 years
      and mean disease duration of 12.9 years. Approximately 72% of patients were on
      methotrexate (76.1% combination therapy), and 36.7% were treated with biologics
      (6.4% monotherapy, 30.3% combination therapy). The agreement with T2T
      recommendations ranged from 8.6 for recommendation 4 (frequency of adjustment of
      drug therapy) to 9.5 for recommendation 8 (maintenance of treatment targets).
      These results are comparable to a previous physicians' survey except that there
      was more acceptance on the part of patients for more frequent visits
      (recommendation 5; patient agreement score was 9.06 vs physician agreement score
      of 6.92) and evaluations for adjustments of therapy (recommendation 6 patient
      agreement score was 9.39 vs physician agreement score of 7.49) to achieve the
      stated goal. CONCLUSIONS: The results of this survey showed that Canadian
      patients are being treated for their RA according to the published treatment
      recommendations with combination disease-modifying antirheumatic drugs and
      biologics and a small percentage with oral corticosteroids. The majority of
      patients seems to be satisfied with their management and is in agreement with the
      T2T recommendations, although they tended to place greater emphasis than did
      physicians on flexibility of visit frequency and detailed assessments.

PMID- 24561408
TI  - Active tuberculosis risk with tumor necrosis factor inhibitors after treating
      latent tuberculosis.
AB  - BACKGROUND: Active tuberculosis (TB) risk increases during anti-tumor necrosis
      factor (TNF) therapy; therefore, latent TB infection (LTBI) screening is
      recommended in potential TNF inhibitor users. It is unclear whether anti-TNF
      therapy increases the risk of active TB infection even after standard LTBI
      treatment. OBJECTIVE: The objective of this study was to compare the risk of
      active TB development in LTBI-positive versus LBTI-negative TNF inhibitor users
      following the current national LTBI treatment guidelines for LTBI. METHODS: We
      retrospectively studied 949 TNF inhibitor users with immune-mediated inflammatory
      diseases from 2005 to 2012 at the Yonsei University Health System. We compared
      the incidence of active TB among LTBI-positive TNF inhibitor users treated
      according to national guidelines (n = 256) and LTBI-negative TNF inhibitor users
      (n = 521), using Poisson regression. RESULTS: The active TB incidence was 1107
      per 100,000 patient-years in LTBI-positive TNF inhibitor users who received
      standard LTBI treatment and 490 per 100,000 patient-years in LTBI-negative TNF
      inhibitor users. Analysis showed that despite this numerical trend active TB risk
      was not statistically significantly elevated in LTBI-positive versus LTBI
      negative TNF inhibitor users (incidence risk ratio, 2.15; P = 0.24; 95%
      confidence interval, 0.6-7.7). CONCLUSIONS: This study demonstrated no
      statistically significantly increased risk of active TB in LTBI-positive TNF
      inhibitor users who received standard LTBI treatment compared with LTBI-negative
      TNF inhibitor users.

PMID- 24561409
TI  - Streptococcus agalactiae: an emerging cause of septic arthritis.
AB  - OBJECTIVE: Invasive Streptococcus agalactiae infection in nonpregnant women has
      been reported increasingly worldwide. This study reports the clinical features
      and outcome of S. agalactiae septic arthritis in Thai patients. METHODS: The
      medical records of cases with septic arthritis seen between July 1990 and
      December 2010 were reviewed. Only those with S. agalactiae were included in this
      study. RESULTS: From 244 cases of septic arthritis, 38 (15.57%, 13 men and 25
      women) were caused by S. agalactiae, with 34 of them (89.48%) occurring between
      2008 and 2010. Their mean age was 52.89 (SD, 18.95) years. Twenty-four of the 38
      patients (63.16%) had 1 or more underlying disease that might predispose to joint
      infection. Fever and joint pain were the most common symptoms presented. Eleven
      cases (28.95%) presented monoarthritis, 15 (39.47%) oligoarthritis, and 12
      (31.58%) polyarthritis, with a mean joint involvement of 3.34 (SD, 2.35) joints
      (range, 1-8). Cellulitis was seen in 27 cases (71.05%). Blood cultures were
      positive in 31 patients (81.58%). Thirty-five of the 38 synovial fluid specimens
      obtained were enough for cultures and stain smears, with 24 (68.57%) growing S.
      agalactiae and 19 (54.29%) showing gram-positive cocci. All isolates were
      sensitive to penicillin. Ten patients (26.31%) received arthroscopic drainage.
      The articular outcome was good in 11 patients, fair in 24, and poor in 3. There
      were no deaths. CONCLUSIONS: Streptococcus agalactiae is an emerging cause of
      septic arthritis in Thai patients. Physicians should be especially aware of this
      condition in patients presenting with acute oligopolyarthritis and prominent
      cellulitis.

PMID- 24561410
TI  - Variations and practice in the care of patients with rheumatoid arthritis:
      quality and cost of care.
AB  - INTRODUCTION: Variability in treatment is linked to lower quality of care and
      higher costs. Rheumatoid arthritis (RA) is a chronic inflammatory disease for
      which care and management may vary considerably among rheumatologists. The extent
      of this variability and its cost ramifications have not been widely studied. This
      prospective study evaluated the quality and variability in care and quantified
      the potential cost implications. METHODS: We used Clinical Performance and
      Value(r) vignettes to measure the quality of RA care among community-based
      rheumatologists. Three online Clinical Performance and Value(r) vignettes-
      representing patients likely seen in practice with mild disease activity (case
      A), worsening disease activity (case B), and stable disease with a complicating
      comorbidity (case C)--were administered to each rheumatologist. Responses were
      scored against evidence-based criteria. Costs were computed using current (2011)
      Medicare pricing. Data were analyzed using t test and fixed-effects analysis of
      variance. RESULTS: One hundred eight board-certified rheumatologists (72% were
      male; mean age, 49.1 years) completed the study. Overall quality scores averaged
      61.3%. Those employed by a health system or in a multispecialty practice were
      more likely to score higher. Highest combined scores for diagnosis and treatment
      were evident with case A (61.7%) and lowest with case C (46.7%). Up to 79% of
      rheumatologists ordered at least 1 laboratory test that was considered
      unnecessary by study protocol criteria, incurring a mean excess cost of $37.85
      per physician per case. Up to 26.9% rheumatologists prescribed biologic agents
      that were not indicated based on American College of Rheumatology treatment
      guidelines, resulting in additional costs of $2041 per patient per month.
      CONCLUSION: In this study, we observed a wide range of reported practice
      variability by rheumatologists in the management of RA. This included unnecessary
      testing and use of biologic agents that increased the costs of treatment.
      Opportunities for quality improvement and cost control exist in the management of
      RA.

PMID- 24561411
TI  - Assessment of fatigue in rheumatoid arthritis (by Functional Assessment of
      Chronic Illness Therapy-Fatigue score) and its relation to disease activity and
      anemia.
AB  - BACKGROUND: Patients with rheumatoid arthritis (RA) mention fatigue as one of
      their most annoying problems. Measuring fatigue, understanding its contributory
      factors, and treating it as a feasible target lead to better patient outcome and
      improved quality of life. The Functional Assessment of Chronic Illness Therapy
      (FACIT) Measurement System is a collection of health-related quality-of-life
      questionnaires targeted to the management of chronic illness. OBJECTIVE: The
      objective of this study was to evaluate fatigue using FACIT-Fatigue (FACIT-F)
      score and its relation to disease activity (using Disease Activity Score [DAS28]
      and Clinical Disease Activity Index [CDAI] score) and anemia in RA patients.
      METHODS: A total of 100 RA patients were evaluated for fatigue using FACIT-F
      score, for disease activity using DAS28 and CDAI scores, for anemia using
      hemoglobin levels. Correlation studies were done using Pearson test. RESULTS:
      Functional Assessment of Chronic Illness Therapy-Fatigue showed positive
      association with DAS28 (P < 0.001; r = -0.80) and CDAI (P < 0.001; r = -0.83).
      Considering various components of DAS28 and CDAI, FACIT-F showed significant
      correlation with tender joint count (P < 0.001; r = -0.73), swollen joint count
      (P < 0.001; r = -0.76), patient global assessment (P < 0.001; r = -0.72), and
      evaluator global assessment (P < 0.001; r = -0.75). Erythrocyte sedimentation
      rate had no association with the fatigue (P = 0.217). No association was observed
      between fatigue and hemoglobin levels (P = 0.203). CONCLUSION: The fatigue
      experienced by the patients with RA is strongly associated with the severity of
      disease activity and is independent of anemia.

PMID- 24561413
TI  - The PANLAR Rheumatology Prize for Latin American rheumatologists: an incentive
      for rheumatologists entering the field: a 5-year report.

PMID- 24561412
TI  - Intra-articular, bursa, and tendon sheath injections: a survey of practice
      patterns among members of the American College of Rheumatology.
AB  - OBJECTIVE: The objective of this study was to survey members of the American
      College of Rheumatology (ACR) regarding intra-articular and soft tissue
      (musculoskeletal [MSK]) injections and to determine if injection techniques vary
      depending on type of practice and years of experience. METHODS: A survey was e
      mailed to the members of the ACR to obtain demographics of the respondents, MSK
      injection practices, and adverse events seen. RESULTS: The most common
      indications for MSK injections were rheumatoid arthritis, osteoarthritis, and
      bursitis. Written consent and time-out procedures were more common in
      academic/government practices when compared with private practice. There was
      variation in the type of corticosteroid used. The most common preparations were
      methylprednisolone actetate (45.0%), triamcinolone acetonide (26.1%),
      triamcinolone hexacetonide (22.1%). This survey showed good agreement on the
      dosage of corticosteroid for MSK injections; however, as years of experience
      increased, clinicians were more likely to prescribe lower doses for shoulder and
      knee injections. CONCLUSIONS: In this survey of ACR members, we found self
      reported differences in the type of corticosteroid used for MSK injections. There
      was general agreement on frequency of injections, but more experienced
      practitioners reported using lower doses of corticosteroid.

PMID- 24561414
TI  - Neutrophilic urticarial dermatosis (NUD) in probable adult-onset Still disease
      responding to anakinra.
AB  - Differential diagnosis of urticarial skin lesions not representing classic
      urticaria remains a challenge. Long-lasting nonpruritic urticarial plaques and
      the histopathologic finding of a dense infiltrate with neutrophil granulocytes
      are indicative for a rare entity within a group of diseases termed neutrophilic
      dermatoses. Here, we report a case of neutrophilic urticarial dermatosis
      characterized by nonpruritic urticarial skin lesions, histopathologic changes
      resembling Sweet syndrome, and simultaneous Still syndrome. After treatment with
      conventional immunosuppressives including systemic corticosteroids without
      disease control, the patient responded to anakinra therapy within days achieving
      complete remission of skin lesions and systemic symptoms including fever and high
      C-reactive protein.

PMID- 24561415
TI  - Hydralazine associated pauci-immune glomerulonephritis.
AB  - Hydralazine is a medication that has been used to manage hypertension and heart
      failure. In this case series, we report 4 patients who presented to a large,
      Midwestern academic medical center on chronic hydralazine therapy with acute
      kidney injury, nephritic urine sediment on urine microscopy, and the simultaneous
      presence of autoantibodies suggesting both drug-induced lupus and drug-induced
      vasculitis. All of them had evidence of pauci-immune glomerulonephritis on kidney
      biopsy. All the patients reported in our series are white women older than 60
      years who were receiving hydralazine for more than 12 months at a dose of 150 mg
      or more. On initial presentation, all had evidence of acute kidney injury with
      nephritic sediment. These patients also had high titers of serum anti-neutrophil
      cytoplasmic antibodies of the antimyeloperoxidase subtype and simultaneous
      presence of multiple autoantibodies. All of them subsequently underwent a kidney
      biopsy, which revealed pauci-immune glomerulonephritis. This case series draws
      rheumatologists' attention to the possibility of pauci-immune glomerulonephritis
      in patients taking hydralazine, highlights the presence of multiple antibodies in
      these cases, and questions the long-term use of hydralazine especially in an
      elderly female population. 

PMID- 24561416
TI  - Interleukin 6 blockade for hyperimmunoglobulin D and periodic fever syndrome.
AB  - Hyperimmunoglobulin D and periodic fever syndrome (HIDS) is a rare,
      autoinflammatory condition caused by mutations in the mevalonate kinase gene.
      There is no standard treatment for HIDS, and randomized controlled trials are
      lacking. Corticosteroids, colchicine, nonsteroidal anti-inflammatory drugs,
      statins, and cyclosporine are of limited efficacy in controlling this condition.
      Recent case reports suggest that most patients respond to etanercept or anakinra.
      Interleukin 6 blockade in HIDS has not been described. We report the case of a 13
      year-old girl with HIDS, who failed to respond to colchicine, corticosteroids,
      etanercept, and anakinra but was successfully treated with the anti-IL-6
      monoclonal antibody, tocilizumab. 

PMID- 24561418
TI  - Sonographic bulge test for small effusion and occult synovitis of the knee.

PMID- 24561417
TI  - A report of the autonomic symptom profile in patients with fibromyalgia.

PMID- 24561419
TI  - An evaluation of high-dose vitamin D for rheumatoid arthritis.

PMID- 24561420
TI  - A benign tumor as the apparent trigger for myopathy.

PMID- 24561421
TI  - Longitudinal melanonychia associated with limited cutaneous systemic sclerosis.

PMID- 24561423
TI  - Successful treatment of refractory adult-onset still disease with canakinumab: a
      case report.

PMID- 24561424
TI  - Molecular effects of the cyanobacterial toxin cyanopeptolin (CP1020) occurring in
      algal blooms: global transcriptome analysis in zebrafish embryos.
AB  - Higher water temperatures due to climate change combined with eutrophication of
      inland waters promote cyanobacterial blooms. Some of the cyanobacteria produce
      toxins leading to drinking water contamination and fish poisoning on a global
      scale. Here, we focused on the molecular effects of the cyanobacterial
      oligopeptide cyanopeptolin CP1020, produced by Microcystis and Planktothrix
      strains, by means of whole-genome transcriptomics. Exposure of 72 hpf old
      zebrafish embryos for 96 h to 100 and 1,000 MUg/L CP1020 resulted in differential
      transcriptional alteration of 396 and 490 transcripts (fold change >= 2),
      respectively, of which 68 gene transcripts were common. These belong to genes
      related to various important biological and physiological pathways. Most clearly
      affected were pathways related to DNA damage recognition and repair, circadian
      rhythm and response to light. Validation by RT-qPCR showed dose-dependent
      transcriptional alterations of genes belonging to DNA damage and repair and
      regulation of circadian rhythm. This leads to the hypothesis that CP1020 acts on
      DNA and has neurotoxic activity. This transcriptome analysis leads to the
      identification of novel and unknown molecular effects of this cyanobacterial
      toxin, including neurotoxicity, which may have important consequences for humans
      consuming contaminated drinking water.

PMID- 24561425
TI  - Effects of depuration on oxidative biomarkers in tilapia (Oreochromis niloticus)
      after subchronic exposure to cyanobacterium producing cylindrospermopsin.
AB  - Cylindrospermopsin (CYN) is a cytotoxic polyketide-derived alkaloid produced by
      several freshwater cyanobacterial species. It is now considered the second most
      studied cyanotoxin worldwide. Among the toxic mechanisms suggested for CYN
      pathogenicity are inhibition of protein and glutathione synthesis, genotoxicity
      by DNA fragmentation, and oxidative stress. The study of depuration of
      cyanobacterial toxins by aquatic organisms, particularly by fish, is important
      for fish economy and public health, but in the case of CYN is practically
      nonexistent. In this work, we investigated the efficiency of two distinct
      depuration periods, 3 or 7d, in a clean environment, as a mean of restoring the
      levels of several oxidative stress biomarkers in tilapia (Oreochromis niloticus)
      subchronically exposed to CYN by immersion in an Aphanizomenon ovalisporum
      culture (by adding 10 MUg CYN/L every two days during 14 d). Lipid peroxidation
      (LPO) and DNA oxidation returned to normal values after 7d of depuration, whereas
      the time needed for restoring of the oxidatively damaged proteins was longer.
      Superoxide dismutase (SOD) and gamma-glutamyl-cysteine-synthetase (gamma-GCS)
      activities recovered after just 3d of depuration, while catalase (CAT) activity
      needed up to 7d to return to control values. Ratio of reduced glutathione to
      oxidized glutathione (GSH/GSSG) returned to control levels after 7d of depuration
      in both organs. These results validate the depuration process as a very effective
      practice for detoxification in fish contaminated with these toxins.

PMID- 24561426
TI  - Identification and characterization of the arsenite methyltransferase from a
      protozoan, Tetrahymena pyriformis.
AB  - Arsenic (As) methylation in aquatic microbes plays a major role in the
      biogeochemistry of As. Protozoa, especially the free-living freshwater species,
      are important players in aquatic ecological health. In this study, an arsenite
      (As(III)) methyltransferase, TpyArsM, was identified and characterized in a free
      living protozoan, Tetrahymena pyriformis. In order to confirm its function,
      TpyarsM gene was knocked-out in Tetrahymena and was also heterologously expressed
      in hypersensitive E. coli; these events resulted in expected decreases in As
      tolerance and methylation ability, respectively. In-vitro tests revealed that
      purified TpyArsM protein methylated inorganic As to mono- and di- methylarsenate,
      and also had the novel property of producing trimethylarsenite (TMA(III)) and
      dimethylarsine (Me2AsH) gases. This new methyltransferase gene, identified in a
      species near the base of the food web, has enriched our knowledge of As
      methyltransferases and has great potential for bioremediation of As-contaminated
      environments.

PMID- 24561427
TI  - Is there a Stobbs factor in atomic-resolution STEM-EELS mapping?
AB  - Recent work has convincingly argued that the Stobbs factor-disagreement in
      contrast between simulated and experimental atomic-resolution images-in ADF-STEM
      imaging can be accounted for by including the incoherent source size in
      simulation. However, less progress has been made for atomic-resolution STEM-EELS
      mapping. Here we have performed carefully calibrated EELS mapping experiments of
      a [101] DyScO3 single-crystal specimen, allowing atomic-resolution EELS signals
      to be extracted on an absolute scale for a large range of thicknesses. By
      simultaneously recording the elastic signal, also on an absolute scale, and using
      it to characterize the source size, sample thickness and inelastic mean free
      path, we eliminate all free parameters in the simulation of the core-loss
      signals. Coupled with double channeling simulations that incorporate both core
      loss inelastic scattering and dynamical elastic and thermal diffuse scattering,
      the present work enables a close scrutiny of the scattering physics in the
      inelastic channel. We found that by taking into account the effective source
      distribution determined from the ADF images, both the absolute signal and the
      contrast in atomic-resolution Dy-M5 maps can be closely reproduced by the double
      channeling simulations. At lower energy losses, discrepancies are present in the
      Sc-L2,3 and Dy-N4,5 maps due to the energy-dependent spatial distribution of the
      background spectrum, core-hole effects, and omitted complexities in the final
      states. This work has demonstrated the possibility of using quantitative STEM
      EELS for element-specific column-by-column atom counting at higher energy losses
      and for atomic-like final states, and has elucidated several possible
      improvements for future theoretical work. 

PMID- 24561429
TI  - Tumour heterogeneity: the cancer kaleidoscope.

PMID- 24561430
TI  - Radiotherapy: change in schedule.

PMID- 24561428
TI  - The role of ventromedial prefrontal cortex in text comprehension inferences:
      semantic coherence or socio-emotional perspective?
AB  - Two hypotheses about the role of the ventromedial prefrontal cortex (vmPFC) in
      narrative comprehension inferences, global semantic coherence versus socio
      emotional perspective, were tested. Seven patients with vmPFC lesions and seven
      demographically matched healthy comparison participants read short narratives.
      Using the consistency paradigm, narratives required participants to make either
      an emotional or visuo-spatial inference, in which a target sentence provided
      consistent or inconsistent information with a previous emotional state of a
      character or a visuo-spatial location of an object. Healthy comparison
      participants made the inferences both for spatial and emotional stories, as shown
      by longer reading times for inconsistent critical sentences. For patients with
      vmPFC lesions, inconsistent sentences were read slower in the spatial stories,
      but not in the emotional ones. This pattern of results is compatible with the
      hypothesis that vmPFC contributes to narrative comprehension by supporting
      inferences about socio-emotional aspects of verbally described situations. 

PMID- 24561431
TI  - Epigenetics: prognosis based on commitment signature.

PMID- 24561433
TI  - Resistance: turning macrophages on, off and on again.

PMID- 24561438
TI  - Rhabdomyosarcoma: flexibility could be important.

PMID- 24561443
TI  - Lymphangiogenesis and lymphatic vessel remodelling in cancer.
AB  - The generation of new lymphatic vessels through lymphangiogenesis and the
      remodelling of existing lymphatics are thought to be important steps in cancer
      metastasis. The past decade has been exciting in terms of research into the
      molecular and cellular biology of lymphatic vessels in cancer, and it has been
      shown that the molecular control of tumour lymphangiogenesis has similarities to
      that of tumour angiogenesis. Nevertheless, there are significant mechanistic
      differences between these biological processes. We are now developing a greater
      understanding of the specific roles of distinct lymphatic vessel subtypes in
      cancer, and this provides opportunities to improve diagnostic and therapeutic
      approaches that aim to restrict the progression of cancer. 

PMID- 24561447
TI  - Possibility of polyunsaturated fatty acids for the prevention and treatment of
      neuropsychiatric illnesses.
AB  - Increasing evidence from the fields of neurophysiology and neuropathology has
      uncovered the role of polyunsaturated fatty acids (PUFA) in protecting neuronal
      cells from oxidative damage, controlling inflammation, regulating neurogenesis,
      and preserving neuronal function. Numerous epidemiological studies have shown
      that deficits in the dietary PUFA docosahexaenoic acid and eicosapentaenoic acid
      are associated with the onset and progression of neuropsychiatric illnesses such
      as dementia, schizophrenia, depression, and posttraumatic stress disorder (PTSD).
      Recent clinical trials have offered compelling evidence that suggests that n-3
      PUFA could reduce depressive, psychotic, and suicidal symptoms, as well as
      aggression. Although many studies have had the validity of their results
      questioned because of small sample size, several studies have indicated that n-3
      PUFA are useful therapeutic tools for the treatment of dementia, major
      depression, bipolar disorder, and PTSD. These findings suggest that the
      pharmacological and nutritional actions of n-3 PUFA may be beneficial in certain
      neuropsychiatric illnesses. This review article outlines the role of PUFA in
      neurodevelopment and the regulatory mechanisms in neuronal stem cell
      differentiation and also the possible use of PUFA as a prescription medicine for
      the prophylaxis or treatment of neuropsychiatric illnesses such as dementia, mood
      disorder, and PTSD. 

PMID- 24561444
TI  - RET revisited: expanding the oncogenic portfolio.
AB  - The RET receptor tyrosine kinase is crucial for normal development but also
      contributes to pathologies that reflect both the loss and the gain of RET
      function. Activation of RET occurs via oncogenic mutations in familial and
      sporadic cancers - most notably, those of the thyroid and the lung. RET has also
      recently been implicated in the progression of breast and pancreatic tumours,
      among others, which makes it an attractive target for small-molecule kinase
      inhibitors as therapeutics. However, the complex roles of RET in homeostasis and
      survival of neural lineages and in tumour-associated inflammation might also
      suggest potential long-term pitfalls of broadly targeting RET. 

PMID- 24561445
TI  - Maintaining and reprogramming genomic androgen receptor activity in prostate
      cancer.
AB  - Prostate cancer treatment is dominated by strategies to control androgen receptor
      (AR) activity. AR has an impact on prostate cancer development through the
      regulation of not only transcription networks but also genomic stability and DNA
      repair, as manifest in the emergence of gene fusions. Whole-genome maps of AR
      binding sites and transcript profiling have shown changes in the recruitment and
      regulatory effect of AR on transcription as prostate cancer progresses. Defining
      other factors that are involved in this reprogramming of AR function gives
      various opportunities for cancer detection and therapeutic intervention. 

PMID- 24561448
TI  - The dignity of the nursing profession: a meta-synthesis of qualitative research.
AB  - BACKGROUND: Nursing continues to gain legitimation epistemologically and
      ontologically as a scientific discipline throughout the world. If a profession
      gains respect as a true autonomous scientific profession, then this recognition
      has to be put in practice in all environments and geographical areas. Nursing
      professional dignity, as a self-regarding concept, does not have a clear
      definition in the literature, and it has only begun to be analyzed in the last 10
      years. OBJECTIVES: The purpose of this meta-synthesis was to determine the
      various factors that constitute the notion of nursing professional dignity. The
      target was to create a tentative model of the concept. RESEARCH DESIGN: The
      research design was a meta-synthesis (N = 15 original articles) of nursing
      professional dignity described in the literature, based on the guidelines by
      Noblit and Hare. METHOD AND FINDINGS: Original studies were sought out from
      electronic databases and manual searches. The selection of literature was
      conducted on stages based on titles (n = 2595), abstracts (n = 70), and full
      texts (n = 15) according to the inclusion and exclusion criteria. From this
      analysis, a clear definition of nursing professional dignity emerged that
      underscored two main macro-dimensions constituting this intertwined,
      multidimensional, and complex notion: characteristics of the human beings and
      workplace elements. CONCLUSION: The recognition of nursing professional dignity
      could have a positive impact on patients because the results clearly showed that
      nurses are more prone to foster patients' dignity, patients' safety, and a better
      quality of care if their own dignity is respected. If nurses are uncomfortable,
      humiliated, or not seen in their professional role, it is difficult to give to
      others good care, good support, or good relationships.

PMID- 24561446
TI  - Thermal ablation of tumours: biological mechanisms and advances in therapy.
AB  - Minimally invasive thermal ablation of tumours has become common since the advent
      of modern imaging. From the ablation of small, unresectable tumours to
      experimental therapies, percutaneous radiofrequency ablation, microwave ablation,
      cryoablation and irreversible electroporation have an increasing role in the
      treatment of solid neoplasms. This Opinion article examines the mechanisms of
      tumour cell death that are induced by the most common thermoablative techniques
      and discusses the rapidly developing areas of research in the field, including
      combinatorial ablation and immunotherapy, synergy with conventional chemotherapy
      and radiation, and the development of a new ablation modality in irreversible
      electroporation. 

PMID- 24561449
TI  - Sensing of barrier tissue disruption with an organic electrochemical transistor.
AB  - The gastrointestinal tract is an example of barrier tissue that provides a
      physical barrier against entry of pathogens and toxins, while allowing the
      passage of necessary ions and molecules. A breach in this barrier can be caused
      by a reduction in the extracellular calcium concentration. This reduction in
      calcium concentration causes a conformational change in proteins involved in the
      sealing of the barrier, leading to an increase of the paracellular flux. To mimic
      this effect the calcium chelator ethylene glycol-bis(beta-aminoethyl ether)
      N,N,N',N'-tetra acetic acid (EGTA) was used on a monolayer of cells known to be
      representative of the gastrointestinal tract. Different methods to detect the
      disruption of the barrier tissue already exist, such as immunofluorescence and
      permeability assays. However, these methods are time-consuming and costly and not
      suited to dynamic or high-throughput measurements. Electronic methods for
      measuring barrier tissue integrity also exist for measurement of the
      transepithelial resistance (TER), however these are often costly and complex. The
      development of rapid, cheap, and sensitive methods is urgently needed as the
      integrity of barrier tissue is a key parameter in drug discovery and
      pathogen/toxin diagnostics. The organic electrochemical transistor (OECT)
      integrated with barrier tissue forming cells has been shown as a new device
      capable of dynamically monitoring barrier tissue integrity. The device is able to
      measure minute variations in ionic flux with unprecedented temporal resolution
      and sensitivity, in real time, as an indicator of barrier tissue integrity. This
      new method is based on a simple device that can be compatible with high
      throughput screening applications and fabricated at low cost.

PMID- 24561450
TI  - Versatile roles of plant NADPH oxidases and emerging concepts.
AB  - NADPH oxidase (NOX) is a key player in the network of reactive oxygen species
      (ROS) producing enzymes. It catalyzes the production of superoxide (O2(-)), that
      in turn regulates a wide range of biological functions in a broad range of
      organisms. Plant Noxes are known as respiratory burst oxidase homologs (Rbohs)
      and are homologs of catalytic subunit of mammalian phagocyte gp91(phox). They are
      unique among other ROS producing mechanisms in plants as they integrate different
      signal transduction pathways in plants. In recent years, there has been addition
      of knowledge on various aspects related to its structure, regulatory components
      and associated mechanisms, and its plethora of biological functions. This update
      highlights some of the recent developments in the field with particular reference
      to important members of the plant kingdom. 

PMID- 24561451
TI  - Polymorphisms and haplotypes of the UDP-glucuronosyltransferase 2B7 gene
      promoter.
AB  - Identification of functional polymorphisms in the UDP-glucuronosyltransferase 2B7
      (UGT2B7) gene predicting interpatient variability in the glucuronidation of drugs
      that are primarily metabolized by UGT2B7 has been the subject of many studies.
      These studies have shown linkage disequilibrium (LD) covering the region from -2
      kb to 16 kb of the UGT2B7 gene. We identified three novel single-nucleotide
      polymorphisms (SNPs) and extended this LD in the 5'-upstream direction to cover
      an additional nine prevalent polymorphisms in the distal -2600- to -4000-base
      pair (bp) promoter. We further showed complete LD between these distal promoter
      SNPs and the SNP (802C>T) in exon 2 in a panel of 26 livers. Because of this LD,
      we showed that all of the 23 prevalent polymorphisms in the 4-kb UGT2B7 promoter
      are linked together, defining two major haplotypes (i.e., I and II). The addition
      of the minor allele of a rare polymorphism and allele exchanges between
      haplotypes I and II generated subhaplotypes of I and II. We demonstrated a higher
      promoter activity of haplotype II over haplotype I, and this higher activity was
      abolished by an A-to-G change at a single SNP (-900A>G). This mutation changed a
      consensus activating protein-1 (AP-1) site (TGAGTCA) as occurred in haplotype II
      to a mutated AP-1 site (TGAGTCG) as occurred in haplotype I. Finally, we showed
      that the previously reported Alu element resides exclusively in haplotype I and
      is a highly conserved CG-rich Alu Y element. 

PMID- 24561452
TI  - Kernel learning at the first level of inference.
AB  - Kernel learning methods, whether Bayesian or frequentist, typically involve
      multiple levels of inference, with the coefficients of the kernel expansion being
      determined at the first level and the kernel and regularisation parameters
      carefully tuned at the second level, a process known as model selection. Model
      selection for kernel machines is commonly performed via optimisation of a
      suitable model selection criterion, often based on cross-validation or
      theoretical performance bounds. However, if there are a large number of kernel
      parameters, as for instance in the case of automatic relevance determination
      (ARD), there is a substantial risk of over-fitting the model selection criterion,
      resulting in poor generalisation performance. In this paper we investigate the
      possibility of learning the kernel, for the Least-Squares Support Vector Machine
      (LS-SVM) classifier, at the first level of inference, i.e. parameter
      optimisation. The kernel parameters and the coefficients of the kernel expansion
      are jointly optimised at the first level of inference, minimising a training
      criterion with an additional regularisation term acting on the kernel parameters.
      The key advantage of this approach is that the values of only two regularisation
      parameters need be determined in model selection, substantially alleviating the
      problem of over-fitting the model selection criterion. The benefits of this
      approach are demonstrated using a suite of synthetic and real-world binary
      classification benchmark problems, where kernel learning at the first level of
      inference is shown to be statistically superior to the conventional approach,
      improves on our previous work (Cawley and Talbot, 2007) and is competitive with
      Multiple Kernel Learning approaches, but with reduced computational expense. 

PMID- 24561453
TI  - Similarity preserving low-rank representation for enhanced data representation
      and effective subspace learning.
AB  - Latent Low-Rank Representation (LatLRR) delivers robust and promising results for
      subspace recovery and feature extraction through mining the so-called hidden
      effects, but the locality of both similar principal and salient features cannot
      be preserved in the optimizations. To solve this issue for achieving enhanced
      performance, a boosted version of LatLRR, referred to as Regularized Low-Rank
      Representation (rLRR), is proposed through explicitly including an appropriate
      Laplacian regularization that can maximally preserve the similarity among local
      features. Resembling LatLRR, rLRR decomposes given data matrix from two
      directions by seeking a pair of low-rank matrices. But the similarities of
      principal and salient features can be effectively preserved by rLRR. As a result,
      the correlated features are well grouped and the robustness of representations is
      also enhanced. Based on the outputted bi-directional low-rank codes by rLRR, an
      unsupervised subspace learning framework termed Low-rank Similarity Preserving
      Projections (LSPP) is also derived for feature learning. The supervised extension
      of LSPP is also discussed for discriminant subspace learning. The validity of
      rLRR is examined by robust representation and decomposition of real images.
      Results demonstrated the superiority of our rLRR and LSPP in comparison to other
      related state-of-the-art algorithms. 

PMID- 24561454
TI  - Tissue-resident T cells lose their S1P1 exit visas.

PMID- 24561455
TI  - Umbilical cord-derived mesenchymal stem cells regulate thymic epithelial cell
      development and function in Foxn1(-/-) mice.
AB  - Thymic microenvironments are essential for the maturation of thymocytes, which
      can be anatomically compartmentalized into cortical and medullar regions. The
      absence of the gene encoding the transcription factor forkhead box n1 (Foxn1)
      causes epithelial differentiation to stall in the precursor stage, resulting in
      the formation of an abnormal thymus. In this study, we used human umbilical cord
      derived mesenchymal stem cells (UC-MSCs) to treat Foxn1(-/-) mice, and then
      analyzed the maturation and distribution of thymic epithelial cells in the Foxn1(
      /-) thymic rudiment and the thymopoiesis of this newly developed rudiment. Our
      data showed a well-organized cortex-medulla architecture and an obvious
      improvement in the maturation of thymic epithelial cells along with the
      appearance of UEA-1(+)MHCII(hi) thymic epithelial cells in the rudiment. We
      further demonstrated improved thymopoiesis and the enhanced export of mature T
      cells with increased numbers of regulatory T cells into the peripheral blood.
      Furthermore, we observed that MSCs can engraft into thymic tissue and express
      many cytokines or proteins, particularly keratinocyte growth factor (KGF) and
      CD248, which are essential for thymic development. Collectively, our data
      identified a new mechanism for MSCs, which may provide a proper microenvironment
      for the reconstitution and functional maturation of the thymus in Foxn1(-/-)
      mice. Additionally, we elicited additional insights into the therapeutic efficacy
      of MSCs in several autoimmune diseases. 

PMID- 24561456
TI  - Runt-related transcription factor 3 is involved in the altered phenotype and
      function in ThPok-deficient invariant natural killer T cells.
AB  - The interplay between the CD4-lineage transcription factor ThPok and the CD8
      lineage transcription factor, runt-related transcription factor 3 (Runx3), in T
      cell development has been extensively documented. However, little is known about
      the roles of these transcription factors in invariant natural killer T (iNKT)
      cell development. CD1d-restricted iNKT cells are committed to the CD4(+)CD8(-)
      and CD4(-)CD8(-) sublineages, which respond to antigen stimulation with rapid and
      potent release of T helper (Th) 1 and Th2 cytokines. However, previous reports
      have demonstrated a new population of CD8(+) NKT cells in ThPok-deficient mice.
      In the current study, we sought to determine whether Runx3 was involved in the re
      expression of CD8 and function of iNKT cells in the absence of ThPok. We used
      mice lacking Runx3, ThPok or both and verified that Runx3 was partially
      responsible for the appearance of CD8(+) iNKT cells in ThPok knockout mice.
      Additionally, Runx3 participated in the immune response mediated by iNKT cells in
      a model of alpha-galactosylceramide-induced acute hepatitis. These results
      indicate that Runx3 is crucial for the phenotypic and functional changes observed
      in ThPok-deficient iNKT cells. 

PMID- 24561457
TI  - The curative effect of fucoidan on visceral leishmaniasis is mediated by
      activation of MAP kinases through specific protein kinase C isoforms.
AB  - Fucoidan can cure both antimony-sensitive and antimony-resistant visceral
      leishmaniasis through immune activation. However, the signaling events underlying
      this cellular response remain uncharacterized. The present study reveals that
      fucoidan induces activation of p38 and ERK1/2 and NF-kappaB DNA binding in both
      normal and Leishmania donovani-infected macrophages, as revealed by western
      blotting and electrophoretic mobility shift assay (EMSA), respectively.
      Pharmacological inhibition of p38, ERK1/2 or the NF-kappaB pathway markedly
      attenuated fucoidan-induced pro-inflammatory cytokine synthesis and inducible
      nitric oxide synthase (iNOS) gene transcription, resulting in a reduction of
      parasite clearance. To decipher the underlying mechanism of fucoidan-mediated
      parasite suppression, the expression and functionality of various protein kinase
      C (PKC) isoforms were evaluated by immunoblotting and enzyme activity assay.
      Fucoidan elicited an increase in expression and activity of PKC-alpha, -betaI and
      -betaII isoforms in infected macrophages. Functional knockdown of PKC-alpha and 
      beta resulted in downregulation of p38 and ERK1/2, along with a marked reduction
      of IL-12 and TNF-alpha production in fucoidan-treated infected macrophages.
      Collectively, these results suggest that the curative effect of fucoidan is
      mediated by PKC-dependent activation of the mitogen-activated protein kinase
      (MAPK)/NF-kappaB pathway, which ultimately results in the production of nitric
      oxide (NO) and disease-resolving pro-inflammatory cytokines. 

PMID- 24561459
TI  - Sensitivity of Hematocrit to Osmotic Effects Induced by Changes in Dialysate
      Conductivity: Implications for Relative Blood Volume Measurement and Control.
AB  - Hemodialysis is accompanied by osmotic perturbations with distinct effects on red
      blood cell, plasma, and blood volumes. A series of in vitro studies was done to
      analyze the separate effect on cell volume. Whole porcine blood was circulated
      through an extracorporeal circulation maintaining a constant blood volume.
      Hemoconcentration was continuously measured by established optical and ultrasonic
      online techniques. Osmotic perturbation was performed by variation of dialysate
      conductivity within the clinical range of 13-15 mS/cm. Blood samples were
      analyzed using a microcentrifuge and a standard cell counter. As dialysate
      conductivity increased, centrifuge hematocrit (in %) decreased with a slope of 
      1.91% per unit of conductivity in mS/cm (r2 = 0.98). At the same time, Coulter
      Counter hematocrit slightly decreased only by -0.18% (r2 = 0.53), while optical
      and ultrasonic hematocrit showed a small increase by 0.44% (r2 = 0.97) and 0.69%
      (r2 = 0.94) per unit of conductivity in mS/cm. The sensitivity to osmotic
      perturbation is consistent with theory and with specific characteristics of
      measuring techniques used in this study. The differences, however, need to be
      considered when comparing measurements obtained by different techniques. Finally,
      devices used for relative blood volume measurement in hemodialysis should be
      insensitive to osmosis-induced changes in red blood cell volume.

PMID- 24561461
TI  - Reflections of the academy--looking back to look ahead.

PMID- 24561458
TI  - Online Hemoglobin and Oxygen Saturation Sensing During Continuous Renal
      Replacement Therapy with Regional Citrate Anticoagulation.
AB  - Optical hemoglobin and oxygen saturation sensor (OHOS) monitor when used in
      combination with other hemodynamic tools may be useful for continuous hemodynamic
      monitoring during ultrafiltration. The stand-alone OHOS monitor can easily be
      deployed predialyzer into the extracorporeal circuit of continuous renal
      replacement therapy (CRRT) systems. To maximize the accuracy of the OHOS in 24 hr
      CRRT systems, clotting in the optical blood chamber and the presensor dilution
      incurred by replacement fluid should be minimized. Sustained low-efficiency
      dialysis (SLED) with regional citrate anticoagulation is a therapy that
      incorporates an OHOS and maintains the overall reliability of hemoglobin (Hb) and
      saturation sensing. The system operates at a blood flow rate of 60 ml/min and a
      fixed acid citrate infusion rate of 150 ml/hr. The presensor dilution incurred by
      concentrated citrate infusion would result in a minimal Hb dilution (<0.7 g/dl)
      while minimizing optical blood chamber clotting during 24 hr SLED. 

PMID- 24561462
TI  - Implementation of a pediatric rapid response team: experience of the Hospital for
      Sick Children in Toronto.
AB  - Rapid Response Systems have been introduced in the last decade to increase
      patient safety and decrease the rate of cardiorespiratory arrest on the hospital
      wards and readmission to the intensive care units. In this article we share our
      experience at the Hospital for Sick Children in Toronto on implementation and
      evolution of a pediatric rapid response team; the process, barriers, and ongoing
      challenges. 

PMID- 24561463
TI  - Managing children with severe acute malnutrition--what's new? A health policy
      perspective.

PMID- 24561464
TI  - Nutrition rehabilitation centers and locally prepared therapeutic food in the
      management of severe acute malnutrition. Pediatrician's perspective.

PMID- 24561465
TI  - Demystifying LMS and BCPE methods of centile estimation for growth and other
      health parameters.
AB  - Lambda-Mu-Sigma and Box-Cox Power Exponential are popular methods for
      constructing centile curves but are difficult to understand for medical
      professionals. As a result, the methods are used by experts only. Non-experts use
      software as a blackbox that can lead to wrong curves. This article explains these
      methods in a simple non-mathematical language so that medical professionals can
      use them correctly and confidently. 

PMID- 24561466
TI  - Screw-worm myiasis of prolapsed rectum.
AB  - BACKGROUND: Wound myiasis in the Indian subcontinent is most commonly caused by
      old world screw-worm (Chrysomya bezziana). CASE REPORT AND MANAGEMENT: A 4-year
      old malnourished girl presented with full thickness rectal prolapse following
      acute diarrhea with a large wound and screwworm myiasis of the rectum. Turpentine
      oil was applied to immobilize the maggots followed by manual extraction. Prolapse
      was successfully treated by manual reduction followed by strapping of the
      buttocks. OUTCOME: Child was thriving well and gained 2 kg weight in follow up
      after two weeks. MESSAGE: Parents should be educated about taking care of
      prolapsed rectum.

PMID- 24561467
TI  - Modified regimen of etanercept for tumor necrosis factor receptor associated
      periodic syndrome (TRAPS) like illness.
AB  - BACKGROUND: TRAPS, an autosomal dominant autoinflammatory disorder occurs due to
      mutations of the TNFRSF1A gene. Mutation negative TRAPS (TRAPS like illness) is
      also known. Anti TNF molecules (etanercept) is the mainstay of therapy. CASE
      CHARACTERISTICS: A 11-year-old boy with a 5 year clinical profile indicative of a
      TRAPS like illness and with negative mutation studies is described. He has been
      followed up for nearly 2 years after starting etanercept. OUTCOME: He had
      sustained response to etanercept which has subsequently been titrated (0.4 mg/kg
      subcutaneously every 23-24 days) to keep him symptom free. MESSAGE: Mutation
      negative cases of TRAPS can be diagnosed with a high index of suspicion.
      Treatment with etanercept is expensive but possibly intervals between doses could
      be titrated to reduce cost.

PMID- 24561468
TI  - Feasibility and acceptability of direct observation of procedural skills to
      improve procedural skills.
AB  - Procedural skill learning is usually unobserved during post graduate training.
      This study is an attempt to evaluate feasibility and acceptability of direct
      observation of procedural skills in a medical school in Northern India for
      postgraduates in Pediatrics. Eighty procedures performed by 15 trainees were
      observed by 9 faculty members. Seven of nine assessors considered direct
      observation to be feasible and non-intrusive in their routine clinical and
      teaching schedule while 5 out of 9 felt that it was time consuming. All fifteen
      trainees felt that direct observation enhanced their procedural skills and wished
      it to be extended to all procedures. 

PMID- 24561469
TI  - Serum alkaline phosphatase for screening of hypovitaminosis D.
AB  - This study assessed the utility of serum alkaline phosphatase as a screening test
      to identify vitamin D deficiency and documented that it was not a useful
      screening tool. 

PMID- 24561470
TI  - Analgesic effect of direct breastfeeding.

PMID- 24561471
TI  - Vitamin D toxicity.

PMID- 24561472
TI  - Vitamin D treatment and toxicity: primum non nocere.

PMID- 24561473
TI  - Methodological issues in iodine deficiency disorders survey.

PMID- 24561474
TI  - Hemorrhagic varicella in a newborn.

PMID- 24561475
TI  - Blue nevus on the scalp.

PMID- 24561476
TI  - Plaque-type polymorphous light eruption.

PMID- 24561477
TI  - Breakdown of phosphatidylserine asymmetry following treatment of erythrocytes
      with lumefantrine.
AB  - BACKGROUND: Lumefantrine, a commonly used antimalarial drug, inhibits hemozoin
      formation in parasites. Several other antimalarial substances counteract
      parasitemia by triggering suicidal death or eryptosis of infected erythrocytes.
      Eryptosis is characterized by cell shrinkage and cell membrane scrambling leading
      to phosphatidylserine-exposure at the erythrocyte surface. Signaling involved in
      eryptosis include increase of cytosolic Ca2+-activity ([Ca2+]i), formation of
      ceramide, oxidative stress and/or activation of p38 kinase, protein kinase C
      (PKC), or caspases. The present study explored, whether lumefantrine stimulates
      eryptosis. METHODS: Cell volume has been estimated from forward scatter,
      phosphatidylserine-exposure from annexin V binding, [Ca2+]i from Fluo3
      fluorescence, reactive oxygen species from 2',7'-dichlorodihydrofluorescein
      diacetate fluorescence, content of reduced glutathione (GSH) from mercury orange
      fluorescence, and ceramide abundance from binding of fluorescent antibodies in
      flow cytometry. RESULTS: A 48 h exposure to lumefantrine (3 ug/mL) was followed
      by a significant increase of annexin-V-binding without significantly altering
      forward scatter, [Ca2+]i, ROS formation, reduced GSH, or ceramide abundance. The
      annexin-V-binding following lumefantrine treatment was not significantly modified
      by p38 kinase inhibitors SB203580 (2 MUM) and p38 Inh III (1 MUM), PKC inhibitor
      staurosporine (1 uM) or pancaspase inhibitor zVAD (1 or 10 uM). CONCLUSIONS:
      Lumefantrine triggers cell membrane scrambling, an effect independent from entry
      of extracellular Ca2+, ceramide formation, ROS formation, glutathione content,
      p38 kinase, PKC or caspases.

PMID- 24561479
TI  - Light influences how the fungal toxin deoxynivalenol affects plant cell death and
      defense responses.
AB  - The Fusarium mycotoxin deoxynivalenol (DON) can cause cell death in wheat
      (Triticum aestivum), but can also reduce the level of cell death caused by heat
      shock in Arabidopsis (Arabidopsis thaliana) cell cultures. We show that 10 MUg
      mL(-1) DON does not cause cell death in Arabidopsis cell cultures, and its
      ability to retard heat-induced cell death is light dependent. Under dark
      conditions, it actually promoted heat-induced cell death. Wheat cultivars differ
      in their ability to resist this toxin, and we investigated if the ability of
      wheat to mount defense responses was light dependent. We found no evidence that
      light affected the transcription of defense genes in DON-treated roots of
      seedlings of two wheat cultivars, namely cultivar CM82036 that is resistant to
      DON-induced bleaching of spikelet tissue and cultivar Remus that is not. However,
      DON treatment of roots led to genotype-dependent and light-enhanced defense
      transcript accumulation in coleoptiles. Wheat transcripts encoding a
      phenylalanine ammonia lyase (PAL) gene (previously associated with Fusarium
      resistance), non-expressor of pathogenesis-related genes-1 (NPR1) and a class III
      plant peroxidase (POX) were DON-upregulated in coleoptiles of wheat cultivar
      CM82036 but not of cultivar Remus, and DON-upregulation of these transcripts in
      cultivar CM82036 was light enhanced. Light and genotype-dependent differences in
      the DON/DON derivative content of coleoptiles were also observed. These results,
      coupled with previous findings regarding the effect of DON on plants, show that
      light either directly or indirectly influences the plant defense responses to
      DON.

PMID- 24561478
TI  - Protein-bound uremic toxins: new culprits of cardiovascular events in chronic
      kidney disease patients.
AB  - Chronic kidney disease (CKD) has been considered a major risk factor for
      cardiovascular diseases. Although great advances have recently been made in the
      pathophysiology and treatment of cardiovascular diseases, CKD remains a major
      global health problem. Moreover, the occurrence rates of cardiovascular events
      among CKD patients increase even in cases in which patients undergo hemodialysis,
      and the mechanisms underlying the so-called "cardiorenal syndrome" are not
      clearly understood. Recently, small-molecule uremic toxins have been associated
      with cardiovascular mortality in CKD and/or dialysis patients. These toxins range
      from small uncharged solutes to large protein-bound structures. In this review,
      we focused on protein-bound uremic toxins, such as indoxyl sulfate and p-cresyl
      sulfate, which are poorly removed by current dialysis techniques. Several studies
      have demonstrated that protein-bound uremic toxins, especially indoxyl sulfate,
      induce vascular inflammation, endothelial dysfunction, and vascular
      calcification, which may explain the relatively poor prognosis of CKD and
      dialysis patients. The aim of this review is to provide novel insights into the
      effects of indoxyl sulfate and p-cresyl sulfate on the pathogenesis of
      atherosclerosis. 

PMID- 24561480
TI  - Robust forward simulations of recurrent hitchhiking.
AB  - Evolutionary forces shape patterns of genetic diversity within populations and
      contribute to phenotypic variation. In particular, recurrent positive selection
      has attracted significant interest in both theoretical and empirical studies.
      However, most existing theoretical models of recurrent positive selection cannot
      easily incorporate realistic confounding effects such as interference between
      selected sites, arbitrary selection schemes, and complicated demographic
      processes. It is possible to quantify the effects of arbitrarily complex
      evolutionary models by performing forward population genetic simulations, but
      forward simulations can be computationally prohibitive for large population sizes
      (>10(5)). A common approach for overcoming these computational limitations is
      rescaling of the most computationally expensive parameters, especially population
      size. Here, we show that ad hoc approaches to parameter rescaling under the
      recurrent hitchhiking model do not always provide sufficiently accurate dynamics,
      potentially skewing patterns of diversity in simulated DNA sequences. We derive
      an extension of the recurrent hitchhiking model that is appropriate for strong
      selection in small population sizes and use it to develop a method for parameter
      rescaling that provides the best possible computational performance for a given
      error tolerance. We perform a detailed theoretical analysis of the robustness of
      rescaling across the parameter space. Finally, we apply our rescaling algorithms
      to parameters that were previously inferred for Drosophila and discuss practical
      considerations such as interference between selected sites. 

PMID- 24561481
TI  - SNP2GO: functional analysis of genome-wide association studies.
AB  - Genome-wide association studies (GWAS) are designed to identify the portion of
      single-nucleotide polymorphisms (SNPs) in genome sequences associated with a
      complex trait. Strategies based on the gene list enrichment concept are currently
      applied for the functional analysis of GWAS, according to which a significant
      overrepresentation of candidate genes associated with a biological pathway is
      used as a proxy to infer overrepresentation of candidate SNPs in the pathway.
      Here we show that such inference is not always valid and introduce the program
      SNP2GO, which implements a new method to properly test for the overrepresentation
      of candidate SNPs in biological pathways. 

PMID- 24561482
TI  - A novel statistical approach for jointly analyzing RNA-Seq data from F1
      reciprocal crosses and inbred lines.
AB  - RNA sequencing (RNA-seq) not only measures total gene expression but may also
      measure allele-specific gene expression in diploid individuals. RNA-seq data
      collected from F1 reciprocal crosses in mice can powerfully dissect strain and
      parent-of-origin effects on allelic imbalance of gene expression. In this
      article, we develop a novel statistical approach to analyze RNA-seq data from F1
      and inbred strains. Method development was motivated by a study of F1 reciprocal
      crosses derived from highly divergent mouse strains, to which we apply the
      proposed method. Our method jointly models the total number of reads and the
      number of allele-specific reads of each gene, which significantly boosts power
      for detecting strain and particularly parent-of-origin effects. The method deals
      with the overdispersion problem commonly observed in read counts and can flexibly
      adjust for the effects of covariates such as sex and read depth. The X chromosome
      in mouse presents particular challenges. As in other mammals, X chromosome
      inactivation silences one of the two X chromosomes in each female cell, although
      the choice of which chromosome to be silenced can be highly skewed by alleles at
      the X-linked X-controlling element (Xce) and stochastic effects. Our model
      accounts for these chromosome-wide effects on an individual level, allowing
      proper analysis of chromosome X expression. Furthermore, we propose a genomic
      control procedure to properly control type I error for RNA-seq studies. A number
      of these methodological improvements can also be applied to RNA-seq data from
      other species as well as other types of next-generation sequencing data sets.
      Finally, we show through simulations that increasing the number of samples is
      more beneficial than increasing the library size for mapping both the strain and
      parent-of-origin effects. Unless sample recruiting is too expensive to conduct,
      we recommend sequencing more samples with lower coverage. 

PMID- 24561484
TI  - Structural biology: activating and guiding Cas9.

PMID- 24561483
TI  - The detection of risk pathways, regulated by miRNAs, via the integration of
      sample-matched miRNA-mRNA profiles and pathway structure.
AB  - The use of genome-wide, sample-matched miRNA (miRNAs)-mRNA expression data
      provides a powerful tool for the investigation of miRNAs and genes involved in
      diseases. The identification of miRNA-regulated pathways has been crucial for
      analysis of the role of miRNAs. However, the classical identification method
      fails to consider the structural information of pathways and the regulation of
      miRNAs simultaneously. We proposed a method that simultaneously integrated the
      change in gene expression and structural information in order to identify
      pathways. Our method used fold changes in miRNAs and gene products, along with
      the quantification of the regulatory effect on target genes, to measure the
      change in gene expression. Topological characteristics were investigated to
      measure the influence of gene products on entire pathways. Through the analysis
      of multiple myeloma and prostate cancer expression data, our method was proven to
      be effective and reliable in identifying disease risk pathways that are regulated
      by miRNAs. Further analysis showed that the structure of a pathway plays a
      crucial role in the recognition of the pathway as a factor in disease risk. 

PMID- 24561485
TI  - Compressed sensing MRI exploiting complementary dual decomposition.
AB  - Compressed sensing (CS) MRI exploits the sparsity of an image in a transform
      domain to reconstruct the image from incoherently under-sampled k-space data.
      However, it has been shown that CS suffers particularly from loss of low-contrast
      image features with increasing reduction factors. To retain image details in such
      degraded experimental conditions, in this work we introduce a novel CS
      reconstruction method exploiting feature-based complementary dual decomposition
      with joint estimation of local scale mixture (LSM) model and images. Images are
      decomposed into dual block sparse components: total variation for piecewise
      smooth parts and wavelets for residuals. The LSM model parameters of residuals in
      the wavelet domain are estimated and then employed as a regional constraint in
      spatially adaptive reconstruction of high frequency subbands to restore image
      details missing in piecewise smooth parts. Alternating minimization of the dual
      image components subject to data consistency is performed to extract image
      details from residuals and add them back to their complementary counterparts
      while the LSM model parameters and images are jointly estimated in a sequential
      fashion. Simulations and experiments demonstrate the superior performance of the
      proposed method in preserving low-contrast image features even at high reduction
      factors. 

PMID- 24561486
TI  - Automatic X-ray landmark detection and shape segmentation via data-driven joint
      estimation of image displacements.
AB  - In this paper, we propose a new method for fully-automatic landmark detection and
      shape segmentation in X-ray images. To detect landmarks, we estimate the
      displacements from some randomly sampled image patches to the (unknown) landmark
      positions, and then we integrate these predictions via a voting scheme. Our key
      contribution is a new algorithm for estimating these displacements. Different
      from other methods where each image patch independently predicts its
      displacement, we jointly estimate the displacements from all patches together in
      a data driven way, by considering not only the training data but also geometric
      constraints on the test image. The displacements estimation is formulated as a
      convex optimization problem that can be solved efficiently. Finally, we use the
      sparse shape composition model as the a priori information to regularize the
      landmark positions and thus generate the segmented shape contour. We validate our
      method on X-ray image datasets of three different anatomical structures: complete
      femur, proximal femur and pelvis. Experiments show that our method is accurate
      and robust in landmark detection, and, combined with the shape model, gives a
      better or comparable performance in shape segmentation compared to state-of-the
      art methods. Finally, a preliminary study using CT data shows the extensibility
      of our method to 3D data. 

PMID- 24561487
TI  - Minimally invasive establishment of murine orthotopic bladder xenografts.
AB  - Orthotopic bladder cancer xenografts are the gold standard to study molecular
      cellular manipulations and new therapeutic agents in vivo. Suitable cell lines
      are inoculated either by intravesical instillation (model of nonmuscle invasive
      growth) or intramural injection into the bladder wall (model of invasive growth).
      Both procedures are complex and highly time-consuming. Additionally, the
      superficial model has its shortcomings due to the lack of cell lines that are
      tumorigenic following instillation. Intramural injection, on the other hand, is
      marred by the invasiveness of the procedure and the associated morbidity for the
      host mouse. With these shortcomings in mind, we modified previous methods to
      develop a minimally invasive approach for creating orthotopic bladder cancer
      xenografts. Using ultrasound guidance we have successfully performed percutaneous
      inoculation of the bladder cancer cell lines UM-UC1, UM-UC3 and UM-UC13 into 50
      athymic nude. We have been able to demonstrate that this approach is time
      efficient, precise and safe. With this technique, initially a space is created
      under the bladder mucosa with PBS, and tumor cells are then injected into this
      space in a second step. Tumor growth is monitored at regular intervals with
      bioluminescence imaging and ultrasound. The average tumor volumes increased
      steadily in in all but one of our 50 mice over the study period. In our
      institution, this novel approach, which allows bladder cancer xenograft
      inoculation in a minimally-invasive, rapid and highly precise way, has replaced
      the traditional model.

PMID- 24561488
TI  - Efficacy of adding once- and thrice-daily voglibose in Japanese type 2 diabetic
      patients treated with alogliptin.
AB  - We investigated the efficacy of once- and thrice-daily voglibose, an alpha
      glucosidase inhibitor, as an add-on therapy to alogliptin, a dipeptidyl peptidase
      4 inhibitor, on glycemic control in Japanese type 2 diabetic patients. In this 12
      week, parallel-group, randomized, open-label, three-arm trial, 151 participants
      treated with alogliptin were randomly allocated to the following three arms; one
      was the group to initiate once-daily voglibose, another was to initiate thrice
      daily voglibose, and the other was the control group. The primary endpoint was
      the change of hemoglobin A1c levels at the end of the study, which was revealed
      to be significantly different among groups (p < 0.001). The once- and thrice
      daily voglibose groups had a significantly greater reduction than the control
      group; the difference was -0.27% and -0.33% in the once- and thrice-daily
      voglibose group, respectively (both p < 0.001). No significant difference was
      observed between the two voglibose groups (p = 0.615). On the other hand, the
      increase of 1,5-anhydroglucitol levels were 3.3 and 5.5 MUg/ml greater in the
      once- and thrice-daily voglibose groups than the control group (both p < 0.001).
      The thrice-daily voglibose group had a greater increase of 1,5- anhydroglucitol
      levels compared to the once-daily voglibose group (p = 0.005). In conclusion,
      once- and thrice-daily voglibose as an add-on to alogliptin significantly
      improved glycemic control in Japanese type 2 diabetic patients. 

PMID- 24561490
TI  - Microglia are polarized to M1 type in high-anxiety inbred mice in response to
      lipopolysaccharide challenge.
AB  - Immune activation in the brain has been shown to contribute to neurodevelopmental
      and pathological progression of mental disorders, and microglia play a central
      role in these processes. But how genetic predisposition and environmental risk
      factors may act in combination to affect microglial activation and the underlying
      molecular mechanisms are largely unclear. In this work, we studied the
      inflammatory profile of microglia across four inbred strains of mice with
      different anxiety traits: C57BL/6J, FVB/N, DBA/2J, and 129S2/Sv. Importantly, we
      found that a high-anxiety strain, naive DBA/2J mice, had significantly more M1
      (MHCII(+)CD206(-))-polarized microglia, whereas another high-anxiety strain,
      naive 129S2/Sv mice, expressed significantly more activated (MHCII(+))
      perivascular macrophages than the other strains. After a systemic LPS challenge,
      polarization to M1 microglia in DBA/2J and 129S2/Sv mice was even more prominent
      than in C57BL/6J and FVB/N mice, and was correlated with their anxiety-like
      behaviors. Macrophage M1/M2 polarization in the spleen showed a similar pattern
      in DBA/2J and 129S2/Sv mice in response to LPS stimulation. Furthermore, DBA/2J
      mice expressed higher mRNA levels of Il1b, Il6, and Tnf, and higher Nos2/Arg1
      ratio but lower Chi3l3 level in the hypothalamus before and after LPS
      stimulation, respectively. In comparison, 129S1/Sv, a sibling line of 129S2/Sv,
      expressed significantly higher levels of other immune-related genes in the brain.
      We further discovered a group of myeloid transcription factors that may underpin
      the strain-specific differences in microglial activation. We conclude that
      proinflammatory microglial activation reflects anxiety traits in mice, especially
      after a peripheral innate immune challenge. Our work sheds new light in
      understanding the potential molecular mechanisms of stress-induced microglial
      activation and polarization. 

PMID- 24561489
TI  - Behavioral and neural effects of intra-striatal infusion of anti-streptococcal
      antibodies in rats.
AB  - Group A beta-hemolytic streptococcal (GAS) infection is associated with a
      spectrum of neuropsychiatric disorders. The leading hypothesis regarding this
      association proposes that a GAS infection induces the production of auto
      antibodies, which cross-react with neuronal determinants in the brain through the
      process of molecular mimicry. We have recently shown that exposure of rats to GAS
      antigen leads to the production of anti-neuronal antibodies concomitant with the
      development of behavioral alterations. The present study tested the causal role
      of the antibodies by assessing the behavior of naive rats following passive
      transfer of purified antibodies from GAS-exposed rats. Immunoglobulin G (IgG)
      purified from the sera of GAS-exposed rats was infused directly into the striatum
      of naive rats over a 21-day period. Their behavior in the induced-grooming,
      marble burying, food manipulation and beam walking assays was compared to that of
      naive rats infused with IgG purified from adjuvant-exposed rats as well as of
      naive rats. The pattern of in vivo antibody deposition in rat brain was evaluated
      using immunofluorescence and colocalization. Infusion of IgG from GAS-exposed
      rats to naive rats led to behavioral and motor alterations partially mimicking
      those seen in GAS-exposed rats. IgG from GAS-exposed rats reacted with D1 and D2
      dopamine receptors and 5HT-2A and 5HT-2C serotonin receptors in vitro. In vivo,
      IgG deposits in the striatum of infused rats colocalized with specific brain
      proteins such as dopamine receptors, the serotonin transporter and other neuronal
      proteins. Our results demonstrate the potential pathogenic role of autoantibodies
      produced following exposure to GAS in the induction of behavioral and motor
      alterations, and support a causal role for autoantibodies in GAS-related
      neuropsychiatric disorders. 

PMID- 24561491
TI  - Local inhibition of hypoxia-inducible factor reduces neointima formation after
      arterial injury in ApoE-/- mice.
AB  - OBJECTIVE: Hypoxia plays a pivotal role in development and progression of
      restenosis after vascular injury. Under hypoxic conditions the hypoxia-inducible
      factors (HIFs) are the most important transcription factors for the adaption to
      reduced oxygen supply. Therefore the aim of the study was to investigate the
      effect of a local HIF-inhibition and overexpression on atherosclerotic plaque
      development in a murine vascular injury model. METHODS AND RESULTS: After wire
      induced vascular injury in ApoE-/- mice a transient, local inhibition of HIF as
      well as an overexpression approach of the different HIF-subunits (HIF-1alpha, HIF
      2alpha) by adenoviral infection was performed. The local inhibition of the HIF
      pathway using a dominant-negative mutant dramatically reduced the extent of
      neointima formation. The diminished plaque size was associated with decreased
      expression of the well-known HIF-target genes vascular endothelial growth factor
      A (VEGF-A) and its receptors Flt-1 and Flk-1. In contrast, the local
      overexpression of HIF-1alpha and HIF-2alpha further increased the plaque size
      after wire-induced vascular injury. CONCLUSIONS: Local HIF-inhibition decreases
      and HIF-alpha overexpression increases the injury induced neointima formation.
      These findings provide new insight into the pathogenesis of atherosclerosis and
      may lead to new therapeutic options for the treatment of in stent restenosis.

PMID- 24561492
TI  - Cardiorespiratory fitness and coronary artery calcification in women.
AB  - INTRODUCTION: Cardiorespiratory fitness (fitness) has been shown to be inversely
      associated with coronary heart disease morbidity and mortality. The
      cardioprotective mechanisms of fitness are not well defined. The goal of this
      study was to assess the relationship between coronary artery calcification as a
      measure of atherosclerotic burden and fitness in a large population of generally
      healthy women. METHODS: 5341 women ages 40-90 years seen between 1997 and 2007
      underwent maximal treadmill exercise testing and coronary artery calcium (CAC)
      scanning. Fitness was reported in METs estimated from maximal treadmill time,
      grade, and speed. CAC was characterized dichotomously as CAC=0 versus CAC>0, and
      CAC<100 versus CAC>=100. Multiple logistic regression models were used to
      calculate the adjusted odds ratio of any CAC (CAC>0) and CAC>=100. Fitness was
      added to these models continuously and categorically based on standard and sample
      specific cut-points. RESULTS: With a mean age of 52.0 years, the overall
      prevalence of detectable CAC was 19.9% and CAC>=100 was 6.8%. Univariable
      analysis showed a modest inverse relationship between fitness and CAC>0 (24% in
      low fit versus 19% in high fit, p-trend=0.006), with a similar trend observed for
      CAC>=100. In multivariable models, age adjustment diminished this association and
      the relationship was no longer statistically significant after adjustment for
      traditional risk factors. CONCLUSIONS: The cardioprotective benefit of fitness
      does not appear to be mediated by an effect independent of traditional risk
      factors on the development of calcified coronary atherosclerosis as measured by
      electron beam tomography.

PMID- 24561494
TI  - Which lipid measurement should we monitor? An analysis of the LIPID study.
AB  - OBJECTIVES: To evaluate the optimal lipid to measure in monitoring patients, we
      assessed three factors that influence the choice of monitoring tests: (1)
      clinical validity; (2) responsiveness to therapy changes and (3) the size of the
      long-term 'signal-to-noise' ratio. DESIGN: Longitudinal analyses of repeated
      lipid measurement over 5 years. SETTING: Subsidiary analysis of a Long-Term
      Intervention with Pravastatin in Ischaemic Disease (LIPID) study-a clinical trial
      in Australia, New Zealand and Finland. PARTICIPANTS: 9014 patients aged 31-75
      years with previous acute coronary syndromes. INTERVENTIONS: Patients were
      randomly assigned to 40 mg daily pravastatin or placebo. PRIMARY AND SECONDARY
      OUTCOME MEASURES: We used data on serial lipid measurements-at randomisation, 6
      months and 12 months, and then annually to 5 years-of total cholesterol; low
      density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol
      and their ratios; triglycerides; and apolipoproteins A and B and their ratio and
      their ability to predict coronary events. RESULTS: All the lipid measures were
      statistically significantly associated with future coronary events, but the
      associations between each of the three ratio measures (total or LDL cholesterol
      to HDL cholesterol, and apolipoprotein B to apolipoprotein A1) and the time to a
      coronary event were better than those for any of the single lipid measures. The
      two cholesterol ratios also ranked highly for the long-term signal-to-noise
      ratios. However, LDL cholesterol and non-HDL cholesterol showed the most
      responsiveness to treatment change. CONCLUSIONS: Lipid monitoring is increasingly
      common, but current guidelines vary. No single measure was best on all three
      criteria. Total cholesterol did not rank highly on any single criterion. However,
      measurements based on cholesterol subfractions-non-HDL cholesterol (total
      cholesterol minus HDL cholesterol) and the two ratios-appeared superior to total
      cholesterol or any of the apolipoprotein options. Guidelines should consider
      using non-HDL cholesterol or a ratio measure for initial treatment decisions and
      subsequent monitoring.

PMID- 24561495
TI  - The routine collection of patient-reported outcome measures (PROMs) for long-term
      conditions in primary care: a cohort survey.
AB  - OBJECTIVES: To evaluate the feasibility of using patient-reported outcome
      measures (PROMs) for long-term conditions (LTCs) in primary care. DESIGN: A
      cohort postal survey conducted from September 2010 to April 2012. SETTING:
      Primary care practices (n=33) in London and the North-West of England.
      PARTICIPANTS: 4484 patients with a diagnosis of asthma, chronic obstructive
      pulmonary disease, diabetes, epilepsy, heart failure or stroke were sent a survey
      at baseline. MAIN OUTCOME: The main outcome was to evaluate the feasibility of
      and the recruitment strategies for collecting PROMs data in LTCs by assessing the
      response rates for the baseline and follow-up surveys. Secondary outcomes were
      the evaluation of change scores of the EQ-5D index and visual analogue scale
      (VAS) between baseline and follow-up surveys. RESULTS: The baseline survey
      achieved a response rate of 38.4% (n=1721/4485) and at follow-up 71.5%
      (n=1136/1589). Response rates varied by LTC. Little change was found in health
      related quality of life for the total sample (-0.001 for the EQ-5D index score
      and 0.12 for the EQ-5D VAS) between patients responding to both the baseline and
      follow-up surveys. CONCLUSIONS: The response rate to the baseline survey was
      similar to that of other general practice surveys. Current UK policy aims to
      assess health service performance in LTCs by means of using PROMs. It thus would
      be desirable to improve response rates by making the invitation to self-reports
      of health-related quality of life more engaging for patients. Results on the EQ
      5D score raise questions about optimal indicators for LTCs and appropriate
      timelines for assessment.

PMID- 24561496
TI  - Non-aristolochic acid prescribed Chinese herbal medicines and the risk of
      mortality in patients with chronic kidney disease: results from a population
      based follow-up study.
AB  - OBJECTIVES: To evaluate the relationship between the use of non-aristolochic acid
      (AA) prescribed Chinese herbal medicines (CHMs) and the risk of mortality in
      patients with chronic kidney disease (CKD). DESIGN: Nationwide population-based
      follow-up study. SETTING: Longitudinal health insurance database sampled from the
      Taiwan National Health Insurance Research Database. PARTICIPANTS: A total of 47
      876 patients with CKD were identified. Participants who had ever used AA
      containing CHMs, had cancer or HIV prior to the diagnosis of CKD, died within the
      first month of CKD diagnosis and who were not Taiwanese citizens were excluded. A
      total of 13 864 participants were eligible for final analysis. PRIMARY AND
      SECONDARY OUTCOME MEASURES: All-cause mortality among patients with CKD between
      2000 and 2008. RESULTS: After controlling for potential confounders, we found
      that participants who started to receive non-AA prescribed CHMs after the
      diagnosis of CKD had a lower risk of mortality as compared with non-users of non
      AA prescribed CHMs (adjusted HR (aHR) 0.6; 95% CI 0.4 to 0.7, p<0.001). Moreover,
      participants who had used non-AA prescribed CHMs prior to and after the diagnosis
      of CKD also had a lower risk of mortality than non-users (aHR 0.6; 95% CI 0.5 to
      0.8, p<0.001). In subgroup analyses, we found that such an inverse association
      was present only among patients who were not eligible to receive erythropoietin
      therapy (ie, serum creatinine ?6 mg/dL and/or haematocrit value ?28%).
      CONCLUSIONS: Patients who received non-AA prescribed CHMs after the diagnosis of
      CKD, yet before the start of erythropoietin therapy had a lower risk of mortality
      than those who did not.

PMID- 24561497
TI  - Depression following fracture in women: a study of age-matched cohorts.
AB  - OBJECTIVES: High levels of disability, functional impairment and mortality are
      independently associated with fracture and depression, however the relationship
      between fracture and depression is uncertain. The aim of this study was to
      investigate whether fracture is associated with subsequent depressive symptoms in
      a population-based sample of women. DESIGN: A study of age-matched fracture
      versus non-fracture cohorts of women. SETTING: Barwon Statistical Division,
      southeastern Australia. PARTICIPANTS: Two samples of women aged >=35 years were
      drawn from the Geelong Osteoporosis Study (GOS). The fracture cohort included
      women with incident fracture identified from radiology reports and the non
      fracture cohort were randomly selected from the electoral roll during 1994-1996.
      OUTCOME MEASURE: Symptoms of depression for women with and without fracture
      during the 12-month period 2000-2001 were identified by self-report questionnaire
      based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth
      Edition (DSM-IV) criteria. RESULTS: A total of 296 women with fracture (12 hip,
      48 vertebral, 91 wrist/forearm, 17 upper arm, 7 pelvis, 11 rib, 62 lower leg and
      48 other fractures) and 590 women without fracture were included. Associations
      between fracture and depression differed between younger (<=65 years) and older
      (>65 years) women. Age and weight-adjusted odds ratio for depression following
      fracture among younger women was 0.62 (0.35 to 1.11, p=0.12) and 3.33 (1.24 to
      8.98, p=0.02) for older women. Further adjustment for lifestyle factors did not
      affect the results. CONCLUSIONS: This study demonstrated that differences in mood
      status exist between older and younger women following fracture and that fracture
      is associated with increased depression in older women. Assessment of mood status
      in both the short and long term following fracture in the elderly seems
      justified, with early detection and treatment likely to result in improved
      outcomes.

PMID- 24561493
TI  - Arterial stiffness and influences of the metabolic syndrome: a cross-countries
      study.
AB  - Specific clusters of metabolic syndrome (MetS) components impact differentially
      on arterial stiffness, indexed as pulse wave velocity (PWV). Of note, in several
      population-based studies participating in the MARE (Metabolic syndrome and
      Arteries REsearch) Consortium the occurrence of specific clusters of MetS
      differed markedly across Europe and the US. The aim of the present study was to
      investigate whether specific clusters of MetS are consistently associated with
      stiffer arteries in different populations. We studied 20,570 subjects from 9
      cohorts representing 8 different European countries and the US participating in
      the MARE Consortium. MetS was defined in accordance with NCEP ATPIII criteria as
      the simultaneous alteration in >=3 of the 5 components: abdominal obesity (W),
      high triglycerides (T), low HDL cholesterol (H), elevated blood pressure (B), and
      elevated fasting glucose (G). PWV measured in each cohort was "normalized" to
      account for different acquisition methods. MetS had an overall prevalence of
      24.2% (4985 subjects). MetS accelerated the age-associated increase in PWV levels
      at any age, and similarly in men and women. MetS clusters TBW, GBW, and GTBW are
      consistently associated with significantly stiffer arteries to an extent similar
      or greater than observed in subjects with alteration in all the five MetS
      components--even after controlling for age, sex, smoking, cholesterol levels, and
      diabetes mellitus--in all the MARE cohorts. In conclusion, different component
      clusters of MetS showed varying associations with arterial stiffness (PWV).

PMID- 24561498
TI  - Should patients with acute coronary disease be stratified for management
      according to their risk? Derivation, external validation and outcomes using the
      updated GRACE risk score.
AB  - OBJECTIVES: Risk scores are recommended in guidelines to facilitate the
      management of patients who present with acute coronary syndromes (ACS).
      Internationally, such scores are not systematically used because they are not
      easy to apply and some risk indicators are not available at first presentation.
      We aimed to derive and externally validate a more accurate version of the Global
      Registry of Acute Coronary Events (GRACE) risk score for predicting the risk of
      death or death/myocardial infarction (MI) both acutely and over the longer term.
      The risk score was designed to be suitable for acute and emergency clinical
      settings and usable in electronic devices. DESIGN AND SETTING: The GRACE risk
      score (2.0) was derived in 32 037 patients from the GRACE registry (14 countries,
      94 hospitals) and validated externally in the French registry of Acute ST
      elevation and non-ST-elevation MI (FAST-MI) 2005. PARTICIPANTS: Patients
      presenting with ST-elevation and non-ST elevation ACS and with long-term
      outcomes. OUTCOME MEASURES: The GRACE Score (2.0) predicts the risk of short-term
      and long-term mortality, and death/MI, overall and in hospital survivors.
      RESULTS: For key independent risk predictors of death (1 year), non-linear
      associations (vs linear) were found for age (p<0.0005), systolic blood pressure
      (p<0.0001), pulse (p<0.0001) and creatinine (p<0.0001). By employing non-linear
      algorithms, there was improved model discrimination, validated externally. Using
      the FAST-MI 2005 cohort, the c indices for death exceeded 0.82 for the overall
      population at 1 year and also at 3 years. Discrimination for death or MI was
      slightly lower than for death alone (c=0.78). Similar results were obtained for
      hospital survivors, and with substitutions for creatinine and Killip class, the
      model performed nearly as well. CONCLUSIONS: The updated GRACE risk score has
      better discrimination and is easier to use than the previous score based on
      linear associations. GRACE Risk (2.0) performed equally well acutely and over the
      longer term and can be used in a variety of clinical settings to aid management
      decisions.

PMID- 24561500
TI  - Mobility of water molecules in the stratum corneum: effects of age and chronic
      exposure to the environment.

PMID- 24561499
TI  - Next generation effects of female adolescent morphine exposure: sex-specific
      alterations in response to acute morphine emerge before puberty.
AB  - Prescription opiate use by adolescent girls has increased significantly in the
      past decade. Preclinical studies using rats report alterations in morphine
      sensitivity in the adult offspring of adolescent morphine-exposed females (MOR
      F1) when compared with the offspring of adolescent saline-exposed females (SAL
      F1). To begin to elucidate the development of these next generation
      modifications, the present study examined the effects of acute morphine
      administration on sedation and corticosterone secretion in prepubescent SAL-F1
      and MOR-F1 male and female rats. In addition, alterations in proopiomelanocortin
      (POMC) gene expression in the arcuate nucleus, as well as in tyrosine hydroxylase
      (TH) and MU-opioid receptor (OPRM1) gene expressions in the ventral tegmental
      area, were analyzed using quantitative PCR, to determine whether differential
      regulation of these genes was correlated with the observed behavioral and/or
      endocrine effects. Increased morphine-induced sedation, coupled with an
      attenuation of morphine-induced corticosterone secretion, was observed in MOR-F1
      males. Significant alterations in both POMC and OPRM1 gene expressions were also
      observed in MOR-F1 males, with no change in TH mRNA expression. Overall, these
      data suggest that the transgenerational effects of adolescent morphine exposure
      can be discerned before pubertal development and are more pronounced in males,
      and suggest dysregulation of the hypothalamic-pituitary-adrenal axis in the
      offspring of adolescent morphine-exposed females. 

PMID- 24561501
TI  - Antimicrobial peptide alamethicin insertion into lipid bilayer: a QCM-D
      exploration.
AB  - Alamethicin is a 20-amino-acid, alpha-helical antimicrobial peptide that is
      believed to kill bacteria through pore formation in the inner membranes. We used
      quartz crystal microbalance with dissipation monitoring (QCM-D) to explore the
      interactions of alamethicin with a supported lipid bilayer. Changes in frequency
      (Deltaf) and dissipation (DeltaD) measured at different overtones as a function
      of peptide concentration were used to infer peptide-induced changes in the mass
      and rigidity of the membrane as well as the orientation of the peptide in the
      bilayer. The measured Deltaf were positive, corresponding to a net mass loss from
      the bilayer, with substantial mass losses at 5 MUM and 10 MUM alamethicin. The
      measured Deltaf at various overtones were equal, indicating that the mass change
      in the membrane was homogeneous at all depths consistent with a vertical peptide
      insertion. Such an orientation coupled to the net mass loss was in agreement with
      cylindrical pore formation and the negligibly small DeltaD suggested that the
      peptide walls of the pores stabilized the surrounding lipid organization.
      Dynamics of the interactions examined through Deltaf vs. DeltaD plots suggested
      that the peptides initially inserted into the membrane and caused disordering of
      the lipids. Subsequently, lipids were removed from the bilayer to create pores
      and alamethicin caused the remaining lipids to reorder and stabilize within the
      membrane. Based on model calculations, we concluded that the QCM-D data cannot
      confirm or rule out whether peptide clusters coexist with pores in the bilayer.
      We have also proposed a way to calculate the peptide-to-lipid ratio (P/L) in the
      bilayer from QCM-D data and found the calculated P/L as a function of the peptide
      concentration to be similar to the literature data for vesicle membranes.

PMID- 24561502
TI  - Effect of graphene oxide on affinity-immobilization of purple membranes on solid
      supports.
AB  - The effect of graphene oxide (GO) on the surface fabrication of purple membranes
      (PM) containing photosensitive bacteriorhodopsin is first reported in this study.
      GO was initially modified with biotin and then coupled with oxidized avidin to
      generate a GO-avidin complex, which was subsequently used as a linker to
      immobilize biotinylated PM (b-PM) onto amine-functionalized supports. Indium-tin
      oxide glass coated with the GO-avidin complex was more hydrophilic than the
      electrode coated only with oxidized avidin, and the successive b-PM adsorption
      yielded a 1.4-fold higher (410 nA/cm(2)) photoelectric activity. AFM analysis on
      mica revealed that the GO-avidin complex layer had less surface roughness and
      dissipation energy than the pure oxidized avidin linker layer. For subsequent b
      PM fabrication, GO addition not only reduced the stacking of immobilized b-PM
      patches but also improved their interior compactness and surface smoothness. This
      study demonstrates a convenient way to introduce GO into PM fabrication
      technology to provide enhanced surface morphology and photoelectric activity.

PMID- 24561503
TI  - Effect of SAM chain length and binding functions on protein adsorption: beta
      lactoglobulin and apo-transferrin on gold.
AB  - Controlled immobilization of proteins is crucial in many applications, including
      biosensors. Allergen biosensing, for example, requires molecular recognition of
      suitably immobilized proteins by specific antibodies and sensitive measurement of
      this interaction. Self-assembled monolayers (SAMs), terminated by active
      functions, and are of great interest for the immobilization of biomolecules. The
      efficiency of further biorecognition involving molecules immobilized on these
      surfaces demonstrates an interesting dependence on the chain length and terminal
      function of the SAM. This motivated us to investigate adsorption of two proteins
      both known as milk allergens-beta-lactoglobulin and apo-transferrin-on amine
      terminated SAMs. We varied the chain length by using either short or long chain
      amine-terminated thiols (cysteamine, CEA, and 11-mercaptoundecylamine, MUAM). We
      also investigated the influence of the addition of a rigid cross-linker, p
      phenylene diisothiocyanate (PDITC), to these amine layers prior to protein
      adsorption. Protein binding was studied using polarization modulation-infrared
      reflection absorption spectroscopy (PM-IRRAS) and atomic force microscopy (AFM)
      to characterize their amount and dispersion. We found that protein immobilization
      varies with SAM chain length and is also influenced by the presence of a cross
      linker. The presence of a rigid cross-linker favours the binding of proteins on
      long chain SAMs, while the effect is almost nonexistent on shorter chains. In
      addition, the presence of the cross-linker induces a better dispersion of the
      proteins on the surfaces, regardless of the length of the thiols forming the
      SAMs. The effects of chain length and chemistry of protein binding are discussed.

PMID- 24561504
TI  - Cotranslational folding inhibits translocation from within the ribosome-Sec61
      translocon complex.
AB  - Eukaryotic secretory proteins cross the endoplasmic reticulum (ER) membrane
      through a protein-conducting channel contained within the ribosome
      Sec61translocon complex (RTC). Using a zinc-finger sequence as a folding switch,
      we show that cotranslational folding of a secretory passenger inhibits
      translocation in canine ER microsomes and in human cells. Folding occurs within a
      cytosolically inaccessible environment, after ER targeting but before initiation
      of translocation, and it is most effective when the folded domain is 15-54
      residues beyond the signal sequence. Under these conditions, substrate is
      diverted into cytosol at the stage of synthesis in which unfolded substrate
      enters the ER lumen. Moreover, the translocation block is reversed by passenger
      unfolding even after cytosol emergence. These studies identify an enclosed
      compartment within the assembled RTC that allows a short span of nascent chain to
      reversibly abort translocation in a substrate-specific manner. 

PMID- 24561506
TI  - Urinary S-phenylmercapturic acid as a key biomarker for measuring occupational
      exposure to low concentrations of benzene in Chinese workers: a pilot study.
AB  - OBJECTIVE: This study analyzed the level of urinary S-phenylmercapturic acid (U
      SPMA) for low benzene exposure in a group of Chinese shoe-making workers.
      METHODS: Urinary samples from 55 workers exposed to benzene at levels lower than
      10 parts per million (ppm) were collected at postshift. U-SPMA level was
      determined using high-performance liquid chromatography/mass spectrography
      (HPLC/MS) method. RESULTS: Good linearity of U-SPMA was observed within the range
      from 10 to 320 MUg/L (r = 0.9994). Concentration of airborne benzene ranged from
      0.71 to 32.17 mg/m3, and three segments were divided with different levels of
      exposure (<=6.0, 6.0 to 10.0, 10 to 32.5 mg/m3), the median U-SPMA concentrations
      were 49.55, 102.15, and 335.69 MUg/g Cr, respectively. CONCLUSION: A good linear
      correlation was found between U-SPMA levels and airborne benzene concentrations.
      The selected method could be applied for detecting other working conditions in
      China.

PMID- 24561505
TI  - Structure of the retinoid X receptor alpha-liver X receptor beta (RXRalpha
      LXRbeta) heterodimer on DNA.
AB  - Nuclear receptors (NRs) are conditional transcription factors with common
      multidomain organization that bind diverse DNA elements. How DNA sequences
      influence NR conformation is poorly understood. Here we report the crystal
      structure of the human retinoid X receptor alpha-liver X receptor beta (RXRalpha
      LXRbeta) heterodimer on its cognate element, an AGGTCA direct repeat spaced by 4
      nt. The complex has an extended X-shaped arrangement, with DNA- and ligand
      binding domains crossed, in contrast to the parallel domain arrangement of other
      NRs that bind an AGGTCA direct repeat spaced by 1 nt. The LXRbeta core binds DNA
      via canonical contacts and auxiliary DNA contacts that enhance affinity for the
      response element. Comparisons of RXRalpha-LXRbetas in the crystal asymmetric unit
      and with previous NR structures reveal flexibility in NR organization and suggest
      a role for RXRalpha in adaptation of heterodimeric complexes to DNA. 

PMID- 24561507
TI  - Construct validity of the individual work performance questionnaire.
AB  - OBJECTIVE: To examine the construct validity of the Individual Work Performance
      Questionnaire (IWPQ). METHODS: A total of 1424 Dutch workers from three
      occupational sectors (blue, pink, and white collar) participated in the study.
      First, IWPQ scores were correlated with related constructs (convergent validity).
      Second, differences between known groups were tested (discriminative validity).
      RESULTS: First, IWPQ scores correlated weakly to moderately with absolute and
      relative presenteeism, and work engagement. Second, significant differences in
      IWPQ scores were observed for workers differing in job satisfaction, and workers
      differing in health. CONCLUSION: Overall, the results indicate acceptable
      construct validity of the IWPQ. Researchers are provided with a reliable and
      valid instrument to measure individual work performance comprehensively and
      generically, among workers from different occupational sectors, with and without
      health problems.

PMID- 24561508
TI  - Metal complexes as structural templates for targeting proteins.
AB  - This article reviews recent advances in the design and discovery of inert metal
      complexes as protein binders. In these metal-based probes or drug candidates, the
      metal is supposed to exert a purely structural role by organizing the
      coordinating ligands in the three dimensional space to achieve a shape and
      functional group complementarity with the targeted protein pockets. Presented
      examples of sandwich, half-sandwich and octahedral d(6)-metal complexes reinforce
      previous perceptions that metal complexes are highly promising scaffolds for the
      design of small-molecule protein binders and complement the molecular diversity
      of organic chemistry by opening untapped chemical space. 

PMID- 24561509
TI  - Issues surrounding postoperative therapy in Crohn's disease to prevent
      recurrence.

PMID- 24561510
TI  - A rare finding on liver explant.

PMID- 24561511
TI  - Selecting the sample.

PMID- 24561512
TI  - Stress and atherosclerotic cardiovascular disease.
AB  - Recent major advances in medical science have introduced a wide variety of
      treatments against atherosclerosis-based cardiovascular diseases, which has led
      to a significant reduction in mortality associated with these diseases. However,
      atherosclerosis-based cardiovascular disease remains a leading cause of death.
      Furthermore, progress in medical science has demonstrated the pathogenesis of
      cardiovascular disease to be complicated, with a wide variety of underlying
      factors. Among these factors, stress is thought to be pivotal. Several types of
      stress are involved in the development of cardiovascular disease, including
      oxidative stress, mental stress, hemodynamic stress and social stress.
      Accumulating evidence indicates that traditional risk factors for
      atherosclerosis, including diabetes, hyperlipidemia, hypertension and smoking,
      induce oxidative stress in the vasculature. Oxidative stress is implicated in the
      pathogenesis of endothelial dysfunction, atherogenesis, hypertension and
      remodeling of blood vessels. Meanwhile, mental stress is a well-known major
      contributor to the development of cardiovascular disease. The cardiovascular
      system is constantly exposed to hemodynamic stress by the blood flow and/or
      pulsation, and hemodynamic stress exerts profound effects on the biology of
      vascular cells and cardiomyocytes. In addition, social stress, such as that due
      to a lack of social support, poverty or living alone, has a negative impact on
      the incidence of cardiovascular disease. Furthermore, there are interactions
      between mental, oxidative and hemodynamic stress. The production of reactive
      oxygen species is increased under high levels of mental stress in close
      association with oxidative stress. These stress responses and their interactions
      play central roles in the pathogenesis of atherosclerosis-based cardiovascular
      disease. Accordingly, the pathophysiological and clinical implications of stress
      are discussed in this article.

PMID- 24561513
TI  - Social Rewards and Social Networks in the Human Brain.
AB  - The rapid development of social media and social networking sites in human
      society within the past decade has brought about an increased focus on the value
      of social relationships and being connected with others. Research suggests that
      we pursue socially valued or rewarding outcomes-approval, acceptance, reciprocity
      as a means toward learning about others and fulfilling social needs of forming
      meaningful relationships. Focusing largely on recent advances in the human
      neuroimaging literature, we review findings highlighting the neural circuitry and
      processes that underlie pursuit of valued rewarding outcomes across non-social
      and social domains. We additionally discuss emerging human neuroimaging evidence
      supporting the idea that social rewards provide a gateway to establishing
      relationships and forming social networks. Characterizing the link between social
      network, brain, and behavior can potentially identify contributing factors to
      maladaptive influences on decision making within social situations.

PMID- 24561514
TI  - Resting-state fMRI: a window into human brain plasticity.
AB  - Although brain plasticity is greatest in the first few years of life, the brain
      continues to be shaped by experience throughout adulthood. Advances in fMRI have
      enabled us to examine the plasticity of large-scale networks using blood oxygen
      level-dependent (BOLD) correlations measured at rest. Resting-state functional
      connectivity analysis makes it possible to measure task-independent changes in
      brain function and therefore could provide unique insights into experience
      dependent brain plasticity in humans. Here, we evaluate the hypothesis that
      resting-state functional connectivity reflects the repeated history of co
      activation between brain regions. To this end, we review resting-state fMRI
      studies in the sensory, motor, and cognitive learning literature. This body of
      research provides evidence that the brain's resting-state functional architecture
      displays dynamic properties in young adulthood. 

PMID- 24561515
TI  - A multicenter study in Spanish, Mexican, and Cuban hospitals of attitude toward
      living kidney donation.
AB  - BACKGROUND: Living kidney donation (LKD) is a treatment with good results,
      although it is not very widely used in Spanish-speaking countries. OBJECTIVE: To
      analyze the attitude toward LKD among hospital personnel in healthcare centers in
      Spain and Latin America. MATERIAL/METHODS: Ten hospitals within the
      "International Collaborative Donor Project" were selected, from Spain, Mexico,
      and Cuba. A random sample was taken, which was stratified according to type of
      service and job category. RESULTS: Of the 2618 workers surveyed, 90% were in
      favor of related LKD, 6% were against it, and the remaining 4% were undecided. If
      the LKD was not related, then 32% were in favor. Other factors associated with a
      favorable attitude toward related LKD were: Working in Latin American hospitals
      (p<0.001); Working in clinical services (p=0.030); Having job stability
      (p=0.013); Having had personal experience of donation and transplantation
      (p=0.002); Being in favor of deceased donation (p<0.001); Considering the
      possibility of needing a transplant (p<0.001); Being in favor of living liver
      donation (p<0.001); Accepting a kidney from a living donor (p<0.001); Having
      spoken about donation and transplantation within family and partner (p<0.001);
      Having carried out pro-social activities (p<0.001); and Having no concern about
      the possible mutilation of the body after donation (p<0.001). CONCLUSIONS:
      Hospital personnel had a favorable attitude toward LKD donation, both in Spain
      and Latin America. This attitude was related with factors of knowledge about and
      general attitude toward organ donation and transplantation, family factors,
      religious factors, and fear about mutilation remaining after the donation.

PMID- 24561516
TI  - Rapid and efficient zebrafish genotyping using PCR with high-resolution melt
      analysis.
AB  - Zebrafish is a powerful vertebrate model system for studying development,
      modeling disease, and performing drug screening. Recently a variety of genetic
      tools have been introduced, including multiple strategies for inducing mutations
      and generating transgenic lines. However, large-scale screening is limited by
      traditional genotyping methods, which are time-consuming and labor-intensive.
      Here we describe a technique to analyze zebrafish genotypes by PCR combined with
      high-resolution melting analysis (HRMA). This approach is rapid, sensitive, and
      inexpensive, with lower risk of contamination artifacts. Genotyping by PCR with
      HRMA can be used for embryos or adult fish, including in high-throughput
      screening protocols.

PMID- 24561517
TI  - ZnO nanoparticle incorporated nanostructured metallic titanium for increased
      mesenchymal stem cell response and antibacterial activity.
AB  - Recent trends in titanium implants are towards the development of nanoscale
      topographies that mimic the nanoscale properties of bone tissue. Although the
      nanosurface promotes the integration of osteoblast cells, infection related
      problems can also occur, leading to implant failure. Therefore it is imperative
      to reduce bacterial adhesion on an implant surface, either with or without the
      use of drugs/antibacterial agents. Herein, we have investigated two different
      aspects of Ti surfaces in inhibiting bacterial adhesion and concurrently
      promoting mammalian cell adhesion. These include (i) the type of nanoscale
      topography (Titania nanotube (TNT) and Titania nanoleaf (TNL)) and (ii) the
      presence of an antibacterial agent like zinc oxide nanoparticles (ZnOnp) on Ti
      nanosurfaces. To address this, periodically arranged TNT (80-120 nm) and non
      periodically arranged TNL surfaces were generated by the anodization and
      hydrothermal techniques respectively, and incorporated with ZnOnp of different
      concentrations (375 MUM, 750 MUM, 1.125 mM and 1.5 mM). Interestingly, TNL
      surfaces decreased the adherence of staphylococcus aureus while increasing the
      adhesion and viability of human osteosarcoma MG63 cell line and human mesenchymal
      stem cells, even in the absence of ZnOnp. In contrast, TNT surfaces exhibited an
      increased bacterial and mammalian cell adhesion. The influence of ZnOnp on these
      surfaces in altering the bacterial and cell adhesion was found to be
      concentration dependent, with an optimal range of 375-750 MUM. Above 750 MUM,
      although bacterial adhesion was reduced, cellular viability was considerably
      affected. Thus our study helps us to infer that nanoscale topography by itself or
      its combination with an optimal concentration of antibacterial ZnOnp would
      provide a differential cell behavior and thereby a desirable biological response,
      facilitating the long term success of an implant. 

PMID- 24561518
TI  - Platelet-derived growth factor-BB is involved in mesenchymal stem cell secretome
      induced neuroprotection of retinal ganglion cells.

PMID- 24561520
TI  - Unique BHLHB3 overexpression in pediatric acute myeloid leukemia with
      t(6;11)(q27;q23).

PMID- 24561521
TI  - Design and characterisation of a thin-film electrode array with shared
      reference/counter electrodes for electrochemical detection.
AB  - In the current study, a novel electrode array and integrated microfluidics have
      been designed and characterised in order to create a sensor chip which is not
      only easy, rapid and cheaper to produce but also have a smaller imprint and good
      electrochemical sensing properties. The current study includes the assessment of
      the effects of an Au quasi-reference electrode and the use of shared
      reference/counter electrodes for the array, in order to obtain a small array that
      can be produced using a fine metal mask. In the study, it is found that when Au
      is used as the quasi-reference electrode, the arrays with shared reference and
      counter electrodes result in faster electron transfer kinetics and prevent the
      potential change with respect to scan rate, and hence is advantageous with
      respect to conventional electrodes. In addition, the resulting novel electrode
      array has been shown to result in higher current density (10.52 uA/cm(2); HRP
      detection assay) and measured diffusion coefficient (14.40*10(-12) cm(2)/s;
      calculated from the data of cyclic voltammetry with 1mM potassium ferricyanide)
      with respect to conventional electrodes tested in the study. Using the new
      electrode arrays, the detection limits obtained from horse radish peroxidase
      (HRP) and bisphenol A assays were 12.5 ng/ml (2.84*10(-10) M ) and 10 ng/ml
      (44*10(-9) M), respectively. Performing the HRP detection assay in a flow
      injection system using array integrated microfluidics provided 25 times lower
      detection limit (11.36*10(-12) M), although Ti has been used as electrode
      material instead of Au. In short, incorporation of this new electrode array to
      lab-on-a-chip or MEMs (micro-electro mechanic systems) technologies may pave the
      way for easy to use automated biosensing devices that could be used for a variety
      of applications from diagnostics to environmental monitoring, and studies will
      continue to move forward in this direction.

PMID- 24561519
TI  - BIM upregulation and ROS-dependent necroptosis mediate the antitumor effects of
      the HDACi Givinostat and Sorafenib in Hodgkin lymphoma cell line xenografts.
AB  - Relapsed/refractory Hodgkin's lymphoma (HL) is an unmet medical need requiring
      new therapeutic options. Interactions between the histone deacetylase inhibitor
      Givinostat and the RAF/MEK/ERK inhibitor Sorafenib were examined in HDLM-2 and L
      540 HL cell lines. Exposure to Givinostat/Sorafenib induced a synergistic
      inhibition of cell growth (range, 70-80%) and a marked increase in cell death (up
      to 96%) due to increased H3 and H4 acetylation and strong mitochondrial injury.
      Gene expression profiling indicated that the synergistic effects of
      Givinostat/Sorafenib treatment are associated with the modulation of cell cycle
      and cell death pathways. Exposure to Givinostat/Sorafenib resulted in sustained
      production of reactive oxygen species (ROS) and activation of necroptotic cell
      death. The necroptosis inhibitor Necrostatin-1 prevented Givinostat/Sorafenib
      induced ROS production, mitochondrial injury, activation of BH3-only protein BIM
      and cell death. Knockdown experiments identified BIM as a key signaling molecule
      that mediates Givinostat/Sorafenib-induced oxidative death of HL cells.
      Furthermore, in vivo xenograft studies demonstrated a 50% reduction in tumor
      burden (P<0.0001), a 5- to 15-fold increase in BIM expression (P < 0.0001) and a
      fourfold increase in tumor necrosis in Givinostat/Sorafenib-treated animals
      compared with mice that received single agents. These results provide a rationale
      for exploring Givinostat/Sorafenib combination in relapsed/refractory HL.

PMID- 24561522
TI  - Ultrasensitive detection of microRNA with isothermal amplification and a time
      resolved fluorescence sensor.
AB  - MicroRNAs (miRNAs) play important roles in a plethora of biological and cellular
      processes. The levels of miRNAs can be useful biomarkers for cellular events or
      disease diagnosis, thus the method for sensitive and selective detection of
      miRNAs is imperative to miRNA discovery, study, and clinical diagnosis. Here we
      develop a novel method to quantify miRNA expression levels as low as attomolar
      sensitivity by two-stage exponential amplification reaction (EXPAR) and a time
      resolved fluorescence sensor in real samples. The method reveals superior
      sensitivity with a detection limit of miRNA of 0.1 aM under pure conditions. The
      method also shows the high selectivity for discriminating differences between
      miRNA family members, thus providing a promising alternative to standard
      approaches for quantitative detection of miRNA.

PMID- 24561523
TI  - Comparing label free electrochemical impedimetric and capacitive biosensing
      architectures.
AB  - The transducer faradaic signals of molecularly receptive interfaces associated
      with specific target binding can be sensitively monitored by electrochemical
      impedance and/or capacitance spectroscopies. A comparative evaluation of both
      impedimetric (associated with charge transfer resistance) and capacitive
      (associated with faradaic density of states) approaches was undertaken using C
      reactive protein (CRP) antigen and antibody interaction as biomolecular binding
      model. Aiming at constructing redox free (impedimetric) and redox tethered
      receptive (capacitive) interfaces engineered by self-assembly monolayer, CRP
      sensitivity and limit of detections were comparatively assessed regarding
      biosensor capabilities. Binding affinity constant between CRP and anti-CRP
      interfacial receptor sites were additionally evaluated by the Langmuir adsorption
      model. Both the impedimetric and capacitive approaches reported similar values of
      experimental analytical parameters albeit the latter was found to have the
      advantage of requiring no solution redox reporter thus making it highly suitable
      for use in multiplexing affinity arrays. 

PMID- 24561524
TI  - A universal electrochemical sensing system for small biomolecules using target
      mediated sticky ends-based ligation-rolling circle amplification.
AB  - A novel versatile electrochemical platform for ultrasensitive detection of small
      biomolecules was developed using ligation-rolling circle amplification (L-RCA)
      with analyte-mediated sticky ends. In order to achieve DNA cyclization, we
      designed two ss-DNA probes: the leftpart probe could form a "hairpin" structure
      by denaturing; the rightpart probe could also form a "hairpin" structure based on
      analyte-activated conformation change. Then the two probes with the same sticky
      ends (G-AATTC) could be ligated in the presence of Escherichia coli DNA ligase,
      forming a circular template for rolling circle amplification (RCA), which could
      be triggered by adding the primer probe and Phi29 DNA polymerase. Electrochemical
      impedance spectroscopy (EIS) was employed as the detection method. Overall, the
      proposed L-RCA-based sensing system not only exhibits excellent analytical
      characteristics with a detection limit of 320 pM and a linear range of 5 orders
      of magnitude (1 nM-10 MUM), but also provides a universal design idea of L-RCA,
      which broadens the use of DNA amplification method and holds great promise in
      ultrasensitive bioassay in the future.

PMID- 24561525
TI  - Magnetic graphene oxide-supported hemin as peroxidase probe for sensitive
      detection of thiols in extracts of cancer cells.
AB  - Magnetic graphene oxide (GO)-hemin probes containing disulfide bonds are simply
      and effectively synthesized through amide reaction to covalently link magnetic
      particles to GO surface and pi-pi stacking interaction between hemin and GO to
      immobilize hemin on GO. Based on the strong nucleophilicity of sulfhydry, we have
      developed a colorimetric detection system for thiols by using glutathione (GSH)
      as a model analyte. Upon the introduction of GSH to the fabricated magnetic
      particle (MP)-GO-hemin probes, the disulfides can be readily reduced by thiols,
      resulting in the release of GO-hemin hybrids to solution. Due to the existence of
      hemin on GO surface, the released GO-hemin that has the intrinsic peroxidase-like
      activity can catalyze the oxidation of ABTS(2-) by H2O2 to form the colored
      radical product ABTS(.-). A broad linear dynamic range of 10(-10) M to 10(-6) M
      GSH is achieved with a detection limit of 8.2*10(-11) M (3sigma). Moreover, the
      new probe is successfully applied to the detection of non-protein thiols and
      protein thiols in the extracts of Ramos cells, which shows favorable
      correlationship with the results obtained by electrochemical method. In addition,
      the MP-GO-hemin probe can detect non-protein thiols in Ramos extracts as low as
      500 cells. In this assay, the prepared MP-GO-hemin conjugates are thoroughly
      characterized by SEM, AFM, UV-Vis, FT-IR, and Raman spectroscopy.

PMID- 24561526
TI  - Fuzzy logic sensing of G-quadruplex DNA and its cleavage reagents based on
      reduced graphene oxide.
AB  - Herein, by combining the merits of nanotechnology and fuzzy logic theory, we
      develop a simple, label-free, and general strategy based on an organic dye
      graphene hybrid system for fluorescence intelligent sensing of G-quadruplexes
      (G4) formation, hydroxyl radical (HO?), and Fe(2+) in vitro. By exploiting
      acridine orange (AO) dyes-graphene as a nanofilter and nanoswitch and the ability
      of graphene to interact with DNA with different structures, our approach can
      efficiently distinguish, quantitatively detect target analytes. In vitro assays
      with G4DNA demonstrated increases in fluorescence intensity of the AO-rGO system
      with a linear range of 16-338 nM and a detection limit as low as 2.0 nM. The
      requenched fluorescence of the G4TBA-AO-rGO system has a non-linear response to
      Fenton reagent. But this requenching reduces the fluorescence intensity in a
      manner proportional to the logarithm to the base 10 of the concentration of
      Fenton reagent in the range of 0.1-100 MUM and 100-2000 MUM, respectively.
      Furthermore, we develop a novel and intelligent sensing method based on fuzzy
      logic which mimics human reasoning, solves complex and non-linear problems, and
      transforms the numerical output into the language description output for
      potential application in biochemical systems, environmental monitoring systems,
      and molecular-level fuzzy logic computing system.

PMID- 24561527
TI  - Transcriptional regulation of fibronectin by p21-activated kinase-1 modulates
      pancreatic tumorigenesis.
AB  - Pancreatic ductal adenocarcinoma (PDAC) is the eighth largest cause of cancer
      related mortality across the world, with a median 5-year survival rate of less
      than 3.5%. This is partly because the molecules and the molecular mechanisms that
      contribute to PDAC are not well understood. Our goal is to understand the role of
      p21-activated kinase 1 (Pak1) signaling axis in the progression of PDAC. Pak1, a
      serine/threonine kinase, is a well-known regulator of cytoskeletal remodeling,
      cell motility, cell proliferation and cell survival. Recent reports suggest that
      Pak1 by itself can have an oncogenic role in a wide variety of cancers. In this
      study, we analyzed the expression of Pak1 in human pancreatic cancer tissues and
      found that Pak1 levels are significantly upregulated in PDAC samples as compared
      with adjacent normals. Further, to study the functional role of Pak1 in
      pancreatic cancer model systems, we developed stable overexpression and
      lentiviral short hairpin RNA-mediated knockdown (KD) clones of Pak1 and studied
      the changes in transforming properties of the cells. We also observed that Pak1
      KD clones failed to form tumors in nude mice. By adopting a quantitative PCR
      array-based approach, we identified fibronectin, a component of the extracellular
      matrix and a mesenchymal marker, as a transcriptional target of Pak1 signaling.
      The underlying molecular mechanism of Pak1-mediated transformation includes its
      nuclear import and recruitment to the fibronectin promoter via interaction with
      nuclear factor-kappaB (NF-kappaB)-p65 complex. To our knowledge, this is the
      first study illustrating Pak1-NF-kappaB-p65-mediated fibronectin regulation as a
      potent tumor-promoting mechanism in KRAS intact model. 

PMID- 24561528
TI  - TMBIM protein family: ancestral regulators of cell death.
AB  - The control of apoptosis in mammals has been historically associated with the
      activity of the BCL-2 family of proteins at the mitochondria. In the past years,
      a novel group of cell death regulators have emerged, known as the Transmembrane
      BAX Inhibitor-1 Motif-containing (TMBIM) protein family. This group of proteins
      is composed of at least six highly conserved members expressed in mammals, with
      homologs in insects, fish, plants, viruses and yeast. Different studies indicate
      that all TMBIM family members have inhibitory activities in different setting of
      apoptosis. Here, we overview and integrate possible mechanisms underlying the
      impact of the TMBIM protein family in the regulation of cell death, which include
      activities at diverse subcellular compartments, including death receptor
      regulation, modulation of endoplasmic reticulum (ER) calcium homeostasis, ER
      stress signaling, autophagy, reactive oxygen species production, among other
      effects. The possible intersection between the BCL-2 and TMBIM family in the
      control of cell death is also discussed, in addition to their implication in the
      progression of cancer.

PMID- 24561530
TI  - Efficiency of anisodamine for organophosphorus-poisoned patients when
      atropinization cannot be achieved with high doses of atropine.
AB  - Poisoning by organophosphorus insecticides is a major global public health
      problem. Although atropine has been widely used to treat organophosphate (OP)
      poisoning, sometimes atropinization cannot be achieved, even with high doses of
      atropine. Hence, we aimed to assess the effect of anisodamine for
      organophosphorus poisoned patients for whom atropinization could not be achieved
      through high doses of atropine. In this study, sixty-four OP-poisoning patients,
      all of whom accepted routine treatments but who did not attain atropinization
      after high doses of atropine for 12 h, were enrolled. The result showed that the
      time to atropinization was 24.3+/-4.3 h in the anisodamine group, significantly
      shorter than in the atropine group (29.2+/-7.0 h, p<0.05); the hospital stay in
      the anisodamine group was 5.3+/-2.5 days, significantly shorter than the 6.9+/
      2.3 days needed by the atropine group (p<0.05). We draw a conclusion that
      anisodamine can shorten the process of atropinization and hospital stay in
      organophosphorus poisoned patients for whom atropinization cannot be achieved
      with high doses of atropine.

PMID- 24561531
TI  - Tissue accumulation and toxicity of isothiazolinone in Ctenopharyngodon idellus
      (grass carp): association with P-glycoprotein expression and location within
      tissues.
AB  - Isothiazolinone is widely used as a broad-spectrum fungicide in various
      industries, such as oil, paper, pesticide, dyes, tanning and cosmetics. There is
      an increasing concern over protection of the aquatic environment due to its large
      scale use. The acute toxicity (LC50) of isothiazolinone in Ctenopharyngodon
      idellus was investigated. The residual time and accumulation in tissues, P
      glycoprotein mRNA level and localization of P-glycoprotein in the liver and
      kidney were also analyzed. The LC50 (48 h) values of isothiazolinone to C.
      idellus were 0.53+/-0.17 mg/L and 0.41+/-0.08 mg/L at 15  degrees C and 25 
      degrees C, respectively. The LC50 values decreased as the temperature increased.
      The accumulation of isothiazolinone in livers and kidneys in the high temperature
      group (25  degrees C) was significantly greater than that of the low temperature
      group (15  degrees C). Prolonged tissue residual time of isothiazolinone was seen
      in all the groups. There were significant differences in P-glycoprotein mRNA
      expression between isothiazolinone-treated groups and control samples (P<0.05
      0.01). Temperature affected accumulation and toxicity of isothiazolinone.

PMID- 24561532
TI  - Hypolipidemic activity of Phellinus rimosus against triton WR-1339 and high
      cholesterol diet induced hyperlipidemic rats.
AB  - Patients with the risk for atherosclerotic disease will be targeted to reduce the
      existing hyperlipidemia. The hypolipidemic activity of Phellinus rimosus was
      studied using triton WR-1339 and high cholesterol diet (HCD) induced models. The
      triton induced elevated lipid profile was attenuated by P. rimosus or standard
      drug atorvastatin. Similarly, administration of P. rimosus along with HCD
      significantly decline serum triglyceride, total cholesterol, low-density
      lipoprotein, with elevating the high-density lipoprotein. Thiobarbituric acid
      reacting substances in heart and liver significantly decreased; where as activity
      of enzymatic antioxidants and level of reduced glutathione were significantly
      increased. In both models, P. rimosus extract showed a significant ameliorative
      effect on the elevated atherogenic index as well as LDL/HDL-C ratio. The
      hypolipidemic activity of P. rimosus can be ascribed to its inhibitory effect on
      the liver HMG CoA reductase activity. The results suggest the possible
      therapeutic potential of this fungus as hypolipidemic agent. 

PMID- 24561529
TI  - Angiogenin promotes tumoral growth and angiogenesis by regulating matrix
      metallopeptidase-2 expression via the ERK1/2 pathway.
AB  - Tumor angiogenesis is essential for tumor growth and metastasis and is dependent
      on key angiogenic factors. Angiogenin (ANG), a 14.2-kDa polypeptide member of the
      RNase A superfamily, is an angiogenic protein that has been reported to be
      upregulated and associated with poor prognosis in some human cancers. The
      mechanisms through which aberrant ANG levels promote specific steps in tumor
      progression are unknown. Here, we show that ANG expression in human tissues is
      strongly correlated with an invasive cancer phenotype. We also show that ANG
      induces cellular survival, proliferation, endothelial tube formation and
      xenograft angiogenesis and growth. Novel mechanistic investigations revealed that
      ANG expression stimulated matrix metallopeptidase-2 (MMP2) expression through the
      phosphorylation of ERK1/2. Targeting ANG in vivo with N65828, a small-molecule
      inhibitor of the ribonucleolytic activity of human ANG, resulted in the
      diminution of xenograft tumoral growth through the inhibition of angiogenesis.
      Our findings support an unrecognized interplay between ANG, ERK1/2 and MMP2 that
      can impact tumor growth and progression. The targeting of ANG and associated
      factors could provide a novel strategy to inhibit tumor establishment and growth.

PMID- 24561533
TI  - A physiologically based toxicokinetic and toxicodynamic model links the tissue
      distribution of benzo[a]pyrene and toxic effects in the scallop Chlamys farreri.
AB  - A physiologically based toxicokinetic and toxicodynamic (PBTK-TD) model was
      developed for benzo[a]pyrene (B[a]P) in scallop Chlamys farreri. The PBTK model
      structure consisted of gill, digestive gland, adductor muscle, hemolymph and
      other tissues. In TD modeling, aryl hydrocarbon hydroxylase (AHH) activity assay,
      comet assay, protein carbonyl measurement and lipid peroxidation level
      determination in digestive gland were used as biomarkers to reflect toxic
      effects. We integrated B[a]P concentration and biomarkers by using sigmoid Emax
      model in digestive gland. The PBTK-TD model predicted the B[a]P concentrations
      within each organ compartment and the toxic effects in digestive gland. The
      results showed that the predicted and measured data in different organs were in
      good agreement and comet assay was considered as the best biomarker. This model
      would serve as a useful tool for pollution monitoring and food security. 

PMID- 24561534
TI  - Effects of subchronic samarium exposure on the histopathological structure and
      apoptosis regulation in mouse testis.
AB  - To evaluate the reproductive toxicity of samarium, a widely used rare earth
      element, male ICR mice were orally exposed to samarium nitrate for 90 days for
      lesion evaluation in the testis. Decreased organ coefficients, disorganized
      seminiferous tubules, and decreased spermatogenic cells and sperm of the testis
      were observed extensively in the treated groups, indicating that the testis is a
      target organ of samarium. Electron microscopy confirmed that the lesions inside
      the spermatogenic cells and sperm mainly included mitochondrial swelling,
      mitochondrial vacuolization, fuzzy nuclear membranes, and marginated chromatin.
      Increased spermatogenic cell apoptosis rate in the testis was confirmed with a
      TUNEL assay. And expression up-regulation of p53 and Bax, and down-regulation of
      Bcl-2 were observed (p<0.05), indicating the apoptosis is related to p53 mediated
      pathway. 

PMID- 24561535
TI  - Antioxidant responses in Carassius auratus and Lolium perenne exposed to the
      laboratory pollution.
AB  - Experiments conducted in the laboratories can produce numerous wastes, which
      could potentially affect the health of the researchers. In this study, the
      antioxidant responses in liver of Carassiua auratus and leaf of Lolium perenne
      were investigated after chronic exposure to the air pollution in four different
      laboratories. The obtained data showed that oxidative stress was induced in some
      laboratories, as indicated by some significantly altered biochemical parameters.
      Additionally, the toxicity order was tentatively proposed based on these
      responses. The results indicated that these biochemical indices can be used as
      the oxidative stress biomarkers to assess the effect of environmental pollution
      on the living organisms, and this study can facilitate the understanding of the
      risk assessment of laboratory pollution. 

PMID- 24561536
TI  - Semiquinone glucoside derivative (SQGD) isolated from Bacillus sp. INM-1 protects
      against gamma radiation-induced oxidative stress.
AB  - In the present study, radioprotective potential of Semiquinone glucoside
      derivative (SQGD) isolated from radioresistant bacterium Bacillus sp. INM-1 was
      evaluated. gamma-Radiation induced protein carbonylation, plasmid DNA damage,
      enzyme functional impairment, lipid peroxidation, HO radicals generation and
      their protection by SQGD was assessed. As a result of SQGD treatment, significant
      inhibition (p<0.05) in protein carbonylation was observed with BSA. SQGD
      treatment was found to restore supercoiled (~70+/-3.21%) form of irradiated
      plasmid DNA against gamma-irradiation. SQGD protects enzymes (EcoR1 and BamH1)
      against radiation-induced dysfunctioning. SQGD significantly inhibited (p<0.05)
      lipid peroxidation in liposomes, brain and liver homogenate. Higher HO(*)
      radicals-averting activity of SQGD was observed in the serum and liver homogenate
      of C57BL/6 mice against H2O2-induced oxidative stress. In conclusion, SQGD
      demonstrates excellent radical-scavenging activity towards bio-macromolecules in
      irradiated environment and can be developed as an ideal radioprotector against
      radiation-induced oxidative stress in future.

PMID- 24561537
TI  - Association between neutrophil-lymphocyte ratio and mitral annular calcification.
AB  - Mitral annular calcification (MAC) is closely related to cardiovascular disorders
      including coronary artery disease, atherosclerosis, heart failure, and stroke.
      The clinical risk factors for cardiovascular diseases, including age, obesity,
      hypertension, hyperlipidemia, and diabetes mellitus, are the same for MAC and
      atherosclerosis. The aim of this study was to assess the neutrophil-lymphocyte
      ratio (NLR), an inflammatory marker, in patients with MAC. The study group
      consisted of 117 patients with MAC. Age and sex-matched control group was
      composed of 38 patients who were admitted to echocardiography laboratory due to
      suspicion of organic heart disease and eventually found to be free of MAC. We
      measured hematological indices in patients and control individuals. NLR ratio was
      significantly higher in patients with MAC than in control individuals (3.3 +/-
      1.8 vs. 1.6 +/- 0.4, respectively; P < 0.001), and NLR ratio was positively
      correlated with MAC (P < 0.001, r = 0.58). Red cell distribution width was also
      significantly higher in patients with MAC than in control individuals (16.2 +/-
      3.3 vs. 13.4 +/- 0.9%, respectively; P < 0.001). We have shown that NLR was
      significantly elevated in patients with MAC and it was correlated with MAC.

PMID- 24561539
TI  - Evolutionary genetics of plant adaptation: insights from new model systems.
AB  - Flowering time and mating system divergence are two of the most common adaptive
      transitions in plants. We review recent progress toward understanding the genetic
      basis of these adaptations in new model plant species. For flowering time, we
      find that individual crosses often reveal a simple genetic basis, but that the
      loci involved almost always vary within species and across environments,
      indicating a more complex genetic basis species-wide. Similarly, the transition
      to self-fertilization is often genetically complex, but this seems to depend on
      the amount of standing variation and time since species divergence. Recent
      population genomic studies also raise doubts about the long-term adaptive
      potential of self-fertilization, providing evidence that purifying selection is
      less effective in highly selfing species. 

PMID- 24561538
TI  - KCNJ2 mutation causes an adrenergic-dependent rectification abnormality with
      calcium sensitivity and ventricular arrhythmia.
AB  - BACKGROUND: KCNJ2 mutations are associated with a variety of inherited arrhythmia
      syndromes including catecholaminergic polymorphic ventricular tachycardia 3.
      OBJECTIVE: To characterize the detailed cellular mechanisms of the clinically
      recognized KCNJ2 mutation R67Q. METHODS: Kir2.1 current density was measured from
      COS-1 cells transiently transfected with wild-type human Kir-2.1 (WT-Kir2.1)
      and/or a heterozygous missense mutation in KCNJ2 (R67Q-Kir2.1) by using the whole
      cell voltage clamp technique. Catecholamine activity was simulated with protein
      kinase A-stimulating cocktail exposure. Phosphorylation-deficient mutants, S425N
      Kir2.1 and S425N-Kir2.1/R67Q-S425N-Kir2.1, were used in a separate set of
      experiments. HA- or Myc-Tag-WT-Kir2.1 and HA-Tag-R67Q-Kir2.1 were used for
      confocal imaging. RESULTS: A 33-year-old woman presented with a catecholaminergic
      polymorphic ventricular tachycardia-like clinical phenotype and was found to have
      KCNJ2 missense mutation R67Q. Treatment with nadolol and flecainide resulted in
      the complete suppression of arrhythmias and symptom resolution. Under baseline
      conditions, R67Q-Kir2.1 expressed alone did not produce inward rectifier current
      while cells coexpressing WT-Kir2.1 and R67Q-Kir2.1 demonstrated the rectification
      index (RI) similar to that of WT-Kir2.1. After PKA stimulation, R67Q-Kir2.1/WT
      Kir2.1 failed to increase peak outward current density; WT-Kir2.1 increased by
      46% (n = 5), while R67Q-Kir2.1/WT-Kir2.1 decreased by 6% (n = 6) (P = .002).
      Rectification properties in R67Q-Kir2.1/WT-Kir2.1 demonstrated sensitivity to
      calcium with a decreased RI in the high-calcium pipette solution (RI 20.3% +/-
      4.1%) than in the low-calcium pipette solution (RI 36.5% +/- 5.7%) (P < .05).
      Immunostaining of WT-Kir2.1 and R67Q-Kir2.1 individually and together showed a
      normal membrane expression pattern and colocalization by using the Pearson
      correlation coefficient. CONCLUSIONS: R67Q-Kir2.1 is associated with an
      adrenergic-dependent clinical and cellular phenotype with rectification
      abnormality enhanced by increased calcium. These findings are a significant
      advancement of our knowledge and understanding of the phenotype-genotype
      relationship of arrhythmia syndromes related to KCNJ2 mutations.

PMID- 24561540
TI  - Intramedullary allograft fibula as a reduction and fixation tool for treatment of
      complex proximal humerus fractures with diaphyseal extension.
AB  - SUMMARY: In this study, we present a novel technique for reduction and fixation
      of complex, unstable proximal humerus fractures with diaphyseal extension with
      the assistance of fibula allograft. We treated 14 patients using this technique
      since 2009 and found that it improves the reduction and enhances fixation while
      making the surgical procedure technically more manageable, and allows for early
      postoperative motion. In the first part of this study, we describe in detail the
      indications and surgical technique applied to these fractures. In the second
      part, we review the clinical and radiographic outcomes of these patients. Using
      this new technique, we have achieved an excellent union rate with minimal
      incidence of complications when treating these challenging fractures.

PMID- 24561542
TI  - The perioperative educational program for improving upper arm dysfunction in
      patients with breast cancer: a controlled trial.
AB  - Most patients who undergo breast cancer surgery suffer from impairment of upper
      extremity function. In this study, we investigated the effectiveness of a
      perioperative educational program for improving upper arm dysfunction in patients
      with breast cancer. This longitudinal controlled study was conducted between
      January 2010 and July 2012. Participants comprised 149 patients with primary
      breast cancer before operation, allocated to intervention and control groups.
      Intervention comprised a 3-month educational program on monitoring arm function
      and exercises for preventing shoulder dysfunction and lymphedema. The control
      group received routine care from on-site staffs. Of the 149 patients analyzed, 69
      underwent axillary lymph node dissection (ALND), and 80 underwent sentinel lymph
      node biopsy (SLNB). The intervention group included 39 patients with ALND and 51
      patients with SLNB, while the control group included 30 patients with ALND and 29
      patients with SLNB. Arm girth, shoulder range of motion (ROM), and grip strength
      were measured before surgery and at 1 week, 1 month and 3 months postoperatively.
      Self-reported questionnaires, the Subjective Perception of Post-Operative
      Functional Impairment of the Arm (SPOFIA) and the Disabilities of the Arm,
      Shoulder and Hand (DASH), were administered at the same time points. Among the
      variables examined, only SPOFIA and grip strength were significantly improved in
      the intervention group with ALND. In contrast, the perioperative educational
      program caused no significant improvement for the patients who underwent the
      surgery with SLNB. Thus, the present program improves the postoperative upper arm
      function and discomfort in breast cancer patients who undergo surgery with ALND. 

PMID- 24561541
TI  - Experience with malleable objects influences shape-based object individuation by
      infants.
AB  - Infants' ability to accurately represent and later recognize previously viewed
      objects, and conversely, to discriminate novel objects from those previously seen
      improves remarkably over the first two years of life. During this time, infants
      acquire extensive experience viewing and manipulating objects and these
      experiences influence their physical reasoning. Here we posited that infants'
      observations of object feature stability (rigid versus malleable) can influence
      the use of those features to individuate two successively viewed objects. We
      showed 8.5-month-olds a series of objects that could or could not change shape,
      then assessed their use of shape as a basis for object individuation. Infants who
      explored rigid objects later used shape differences to individuate objects;
      however, infants who explored malleable objects did not. This outcome suggests
      that the latter infants did not take into account shape differences during the
      physical reasoning task and provides further evidence that infants' attention to
      object features can be readily modified based on recent experiences.

PMID- 24561543
TI  - Anger is a distinctive feature of epilepsy patients with depression.
AB  - Controversy exists regarding the similarity between depression as seen in
      patients with epilepsy and in those with idiopathic major depression. The
      objective of this study was to examine whether anger is a distinctive feature of
      depression in epilepsy. Participants included 487 adult patients with epilepsy
      (study group) and 85 patients with idiopathic major depression according to
      Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV)
      criteria, and without other neurological complications (control group). All
      participants completed the Inventory of Depressive Symptomatology Self-Report
      (IDS-SR) and the Buss-Perry Aggression Questionnaire (BAQ). The IDS-SR is a self
      report questionnaire that measures depression severity and assesses all symptoms
      of depression as defined by the DSM-IV. The BAQ is a self-rating scale designed
      for assessing aggression. After examining potential confounding factors (i.e.,
      demographic and clinical variables) using a multivariate linear regression model,
      BAQ scores were compared between the study (n = 85) and control groups (n = 54)
      for patients with moderate or severe depression using established cut-off points
      (IDS-SR score > 25). BAQ scores were significantly higher in the study group (P =
      0.009). Among the BAQ subscales, only anger showed a statistically significant
      difference (P = 0.013). Although a significant correlation was revealed between
      the IDS-SR and BAQ scores in the study group, no such correlation was found in
      the control group. Thus, anger might be a constituent component of depression
      among epilepsy patients, but not among idiopathic major depression patients. 

PMID- 24561544
TI  - An image analysis method to quantify CFTR subcellular localization.
AB  - Aberrant protein subcellular localization caused by mutation is a prominent
      feature of many human diseases. In Cystic Fibrosis (CF), a recessive lethal
      disorder that results from dysfunction of the Cystic Fibrosis Transmembrane
      Conductance Regulator (CFTR), the most common mutation is a deletion of
      phenylalanine-508 (pF508del). Such mutation produces a misfolded protein that
      fails to reach the cell surface. To date, over 1900 mutations have been
      identified in CFTR gene, but only a minority has been analyzed at the protein
      level. To establish if a particular CFTR variant alters its subcellular
      distribution, it is necessary to quantitatively determine protein localization in
      the appropriate cellular context. To date, most quantitative studies on CFTR
      localization have been based on immunoprecipitation and western blot. In this
      work, we developed and validated a confocal microscopy-image analysis method to
      quantitatively examine CFTR at the apical membrane of epithelial cells. Polarized
      MDCK cells transiently transfected with EGFP-CFTR constructs and stained for an
      apical marker were used. EGFP-CFTR fluorescence intensity in a region defined by
      the apical marker was normalized to EGFP-CFTR whole cell fluorescence intensity,
      rendering "apical CFTR ratio". We obtained an apical CFTR ratio of 0.67 +/- 0.05
      for wtCFTR and 0.11 +/- 0.02 for pF508del. In addition, this image analysis
      method was able to discriminate intermediate phenotypes: partial rescue of the
      pF508del by incubation at 27  degrees C rendered an apical CFTR ratio value of
      0.23 +/- 0.01. We concluded the method has a good sensitivity and accurately
      detects milder phenotypes. Improving axial resolution through deconvolution
      further increased the sensitivity of the system as rendered an apical CFTR ratio
      of 0.76 +/- 0.03 for wild type and 0.05 +/- 0.02 for pF508del. The presented
      procedure is faster and simpler when compared with other available methods and it
      is therefore suitable as a screening method to identify mutations that completely
      or mildly affect CFTR processing. Moreover, it could be extended to other studies
      on the biology underlying protein subcellular localization in health and disease.

PMID- 24561545
TI  - Cysteinyl leukotriene receptor antagonist regulates allergic airway inflammation
      in an organ- and cytokine-specific manner.
AB  - BACKGROUND: Cysteinyl leukotrienes (cys-LTs) are very important factors in the
      pathophysiology of bronchial asthma. Cys-LT receptor antagonists (LTRAs) decrease
      allergic airway inflammation. The aim of the present study was to determine the
      differential effects of LTRAs and corticosteroids on allergic airway inflammation
      and allergen-specific cytokine production from lymphoid tissues using a murine
      model of asthma. MATERIAL AND METHODS: Four groups of female BALB/c mice [control
      (Cont); Dermatophagoides farinae allergen-sensitized (AS); pranlukast (Prl), an
      LTRA-treated AS; and dexamethasone (Dex)-treated AS] were examined. Lung
      pathology and cytokine production by prepared mononuclear cells isolated from
      mediastinal lymph nodes (MLNs) and spleen were compared among these groups.
      RESULTS: AS mice exhibited allergic airway inflammation and significant increases
      in allergen-specific Th1 and Th2 cytokines in MLNs and spleen. Prl-treated mice
      showed significant attenuation of allergic airway inflammation concomitant with
      reduction of Th2 cytokines and IFN-g in MLNs but not in spleen. In contrast, Dex
      significantly decreased Th1 and Th2 cytokines in MLNs and also decreased them
      (except IL-13 and IL-2) in spleen. CONCLUSIONS: The inflammatory effects of cys
      LTs could differ in lymphoid organs. LTRAs potentially regulate allergic airway
      inflammation in an organ- and cytokine-specific manner, while systemic
      corticosteroid shows nonspecific effects.

PMID- 24561546
TI  - Carotid surgery affects plasma kynurenic acid concentration: a pilot study.
AB  - BACKGROUND: An increase in plasma kynurenic acid (KYNA) concentration has been
      observed following surgery, inflammation, and cerebral pathologies. The aim of
      the present study was to analyze the changes in plasma KYNA concentration in
      patients undergoing carotid surgery (CS). MATERIAL AND METHODS: Adult patients
      undergoing elective carotid endarterectomy (CEA) or carotid angioplasty with
      stent placement (CAS) were studied. Plasma KYNA concentrations were analyzed
      before surgery and at 4 time points after CS. The amount of inflammation was
      measured as neutrophil-lymphocyte ratio (NLR). RESULTS: Forty patients (10 female
      and 30 male) aged 55-86 years of age were evaluated in this study. In patients
      with unstable carotid plaque, the plasma KYNA concentration was higher than in
      patients with stable carotid plaque. Moreover, the NLR was significantly higher
      in patients with unstable carotid plaque undergoing CEA than in patients
      undergoing CAS. Plasma KYNA concentration increased after surgery in patients
      undergoing CEA and CAS. There was a strong correlation between plasma KYNA
      concentration and NLR in patients with postoperative neurological disorders.
      CONCLUSIONS: CS increases plasma KYNA concentration, and changes in plasma KYNA
      concentration can indicate neurologic outcomes in patients undergoing CS.

PMID- 24561547
TI  - Is there a period of liability with initiation of warfarin in patients with
      atrial fibrillation?

PMID- 24561548
TI  - Efficacy and safety of apixaban compared with warfarin according to age for
      stroke prevention in atrial fibrillation: observations from the ARISTOTLE trial.
AB  - AIMS: The risk of stroke in patients with atrial fibrillation (AF) increases with
      age. In the ARISTOTLE trial, apixaban when compared with warfarin reduced the
      rate of stroke, death, and bleeding. We evaluated these outcomes in relation to
      patient age. METHODS AND RESULTS: A total of 18 201 patients with AF and a raised
      risk of stroke were randomized to warfarin or apixaban 5 mg b.d. with dose
      reduction to 2.5 mg b.d. or placebo in 831 patients with >=2 of the following
      criteria: age >=80 years, body weight <=60 kg, or creatinine >=133 MUmol/L. We
      used Cox models to compare outcomes in relation to patient age during 1.8 years
      median follow-up. Of the trial population, 30% were <65 years, 39% were 65 to
      <75, and 31% were >=75 years. The rates of stroke, all-cause death, and major
      bleeding were higher in the older age groups (P < 0.001 for all). Apixaban was
      more effective than warfarin in preventing stroke and reducing mortality across
      all age groups, and associated with less major bleeding, less total bleeding, and
      less intracranial haemorrhage regardless of age (P interaction >0.11 for all).
      Results were also consistent for the 13% of patients >=80 years. No significant
      interaction with apixaban dose was found with respect to treatment effect on
      major outcomes. CONCLUSION: The benefits of apixaban vs. warfarin were consistent
      in patients with AF regardless of age. Owing to the higher risk at older age, the
      absolute benefits of apixaban were greater in the elderly.

PMID- 24561549
TI  - Clinical efficacy of generic imatinib.
AB  - BACKGROUND: Generic imatinib has recently been approved for chronic myeloid
      leukemia in Canada and the European Union (EU). There are anecdotal concerns of
      reduced efficacy related to generic vs. brand name imatinib. METHODS: MEDLINE and
      EMBASE were searched. Generic imatinib product monographs approved by Health
      Canada and the European Medicines Agency (EMA) were reviewed. Medical information
      of Novartis, Teva and Apotex were contacted. RESULTS: Several issues have been
      raised. First, generic imatinib approved outside Canada and the European Union
      has been associated with reduced efficacy in small case reports and contradictory
      findings with two case series. However, the clinical bioequivalence of these
      generic products has not been clearly established. Secondly, use of generic
      imatinib in other populations has been questioned. However, imatinib absorption
      is not significantly different in pediatric chronic myeloid leukemia or patients
      with gastrointestinal tumours compared to adults with chronic myeloid leukemia.
      Although reduced absorption was reported after gastric bypass and gastrectomy,
      imatinib absorption occurs mostly in the ileum, duodenum, colon and jejunum.
      Change in gastric acidity has also been shown to not affecting imatinib
      absorption. Finally, beta-crystal form of brand name imatinib is more stable than
      the alpha-crystal form of generic imatinib at room temperature. However, the EMA
      found both crystal forms to be highly soluble and polymorphism would not
      significantly influence the performance of generic imatinib. CONCLUSION: Overall,
      anecdotal concerns appear to be unfounded for generic imatinib approved in Canada
      and the EU. There is no evidence that these generic imatinib products are less
      effective than brand name imatinib.

PMID- 24561550
TI  - Differential labeling of cell-surface and internalized proteins after antibody
      feeding of live cultured neurons.
AB  - In order to demonstrate the cell-surface localization of a putative transmembrane
      receptor in cultured neurons, we labeled the protein on the surface of live
      neurons with a specific primary antibody raised against an extracellular portion
      of the protein. Given that receptors are trafficked to and from the surface, if
      cells are permeabilized after fixation then both cell-surface and internal
      protein will be detected by the same labeled secondary antibody. Here, we adapted
      a method used to study protein trafficking ("antibody feeding") to differentially
      label protein that had been internalized by endocytosis during the antibody
      incubation step and protein that either remained on the cell surface or was
      trafficked to the surface during this period. The ability to distinguish these
      two pools of protein was made possible through the incorporation of an overnight
      blocking step with highly-concentrated unlabeled secondary antibody after an
      initial incubation of unpermeabilized neurons with a fluorescently-labeled
      secondary antibody. After the blocking step, permeabilization of the neurons
      allowed detection of the internalized pool with a fluorescent secondary antibody
      labeled with a different fluorophore. Using this technique we were able to obtain
      important information about the subcellular location of this putative receptor,
      revealing that it was, indeed, trafficked to the cell-surface in neurons. This
      technique is broadly applicable to a range of cell types and cell-surface
      proteins, providing a suitable antibody to an extracellular epitope is available.

PMID- 24561551
TI  - The roles of a novel anti-inflammatory factor, milk fat globule-epidermal growth
      factor 8, in patients with coronary atherosclerotic heart disease.
AB  - OBJECTIVE: Inflammation is now considered a main pathogenic factor in coronary
      atherosclerotic heart disease (CHD), and it has a positive correlation with
      plaque vulnerability. A novel anti-inflammatory factor, milk fat globule
      epidermal growth factor 8 (MFG-E8), has been reported as having prominent anti
      inflammatory effects in sepsis. However, few studies have reported on the
      association between MFG-E8 and CHD. In the present study, we aimed to investigate
      the serum MFG-E8 concentrations in patients with different stages of CHD or
      without CHD. Then, we studied the associations among MFG-E8, Gensini score, and
      high-sensitivity C-reactive protein (hs-CRP) in Chinese patients with CHD to
      illustrate the role of MFG-E8 in CHD. METHODS: A total of 176 controls and 295
      patients with CHD were selected for this study. To evaluate CHD severity, we
      calculated the Gensini score for all of the subjects. Serum levels of MFG-E8 were
      determined by an enzyme-linked immunosorbent assay (ELISA) kit; serum total
      cholesterol (TC), high density lipoprotein-cholesterol (HDL-c), low density
      lipoprotein-cholesterol (LDL-c), triglyceride (TG), and hs-CRP were detected by
      an automatic biochemistry analyzer; and fibrinogen (FIB) was analyzed with an
      automatic coagulation analyzer. RESULTS: Compared with the controls, the CHD
      group had a lower level of MFG-E8 (673.20+/-112.34 ng/mL vs. 134.89+/-4.74 ng/mL,
      p<0.001). The level of serum MFG-E8 in the acute myocardial infarction group
      (118.07+/-10.10 ng/mL) was significantly less than that in the stable angina
      group (p=0.025). Further analysis showed that MFG-E8 had a negative association
      with the Gensini score and the hs-CRP level (r=-0.590, p<0.001; r=-0.105,
      p=0.022, respectively). In addition, multiple regression analysis of the
      association between MFG-E8 and the main cardiovascular risk factors in our cases
      showed that MFG-E8 had a negative association with hs-CRP and a positive
      association with LDL-c (all p<0.05). CONCLUSION: The serum level of MFG-E8 was
      negatively associated with the severity of coronary artery stenosis and the risk
      of clinical events. Thus, MFG-E8 has the potential to be a marker of vascular
      complications.

PMID- 24561553
TI  - Self-formation of sub-10 nm nanogaps based on silicidation.
AB  - We have developed a simple and reliable method for the fabrication of sub-10 nm
      wide nanogaps. The self-formed nanogap is based on the stoichiometric solid-state
      reaction between metal and silicon atoms during the silicidation process. The
      nanogap width is determined by the metal layer thickness. Our proposed method can
      produce symmetric and asymmetric electrode nanogaps, as well as multiple nanogaps
      within one unique process step, for potential application to biological/chemical
      sensors and nanoelectronics, such as resistive switches, storage devices, and
      vacuum channel transistors. This method provides high throughput and it is
      suitable for large-scale production. 

PMID- 24561552
TI  - RYR3 gene variants in subclinical atherosclerosis among HIV-infected women in the
      Women's Interagency HIV Study (WIHS).
AB  - BACKGROUND: Single nucleotide polymorphisms (SNPs) in the Ryanodine receptor 3
      (RYR3) gene are associated with common carotid intima media thickness (CCA cIMT)
      in HIV-infected men. We evaluated SNPs in the RYR3 gene among HIV-infected women
      participating in Women's Interagency HIV Study (WIHS). METHODS: CCA cIMT was
      measured using B-mode ultrasound and the 838 SNPs in the RYR3 gene region were
      genotyped using the Illumina HumanOmni2.5-quad beadchip. The CCA cIMT genetic
      association was assessed using linear regression analyses among 1213 women and
      also separately among White (n=139), Black (n=720) and Hispanic (n=354) women
      after adjusting for confounders. A summary measure of pooled association was
      estimated using a meta-analytic approach by combining the effect estimates from
      the three races. Haploblocks were inferred using Gabriel's method and haplotype
      association analyses were conducted among the three races separately. RESULTS:
      SNP rs62012610 was associated with CCA cIMT among the Hispanics (p=4.41*10(-5)),
      rs11856930 among Whites (p=5.62*10(-4)), and rs2572204 among Blacks (p=2.45*10(
      3)). Meta-analysis revealed several associations of SNPs in the same direction
      and of similar magnitude, particularly among Blacks and Hispanics. Additionally,
      several haplotypes within three haploblocks containing SNPs previously related
      with CCA cIMT were also associated in Whites and Hispanics. DISCUSSION:
      Consistent with previous research among HIV-infected men, SNPs within the RYR3
      region were associated with subclinical atherosclerosis among HIV-infected women.
      Allelic heterogeneity observed across the three races suggests that the
      contribution of the RYR3 gene to CCA cIMT is complex, and warrants future studies
      to better understand regional SNP function.

PMID- 24561554
TI  - The binary protein-protein interaction landscape of Escherichia coli.
AB  - Efforts to map the Escherichia coli interactome have identified several hundred
      macromolecular complexes, but direct binary protein-protein interactions (PPIs)
      have not been surveyed on a large scale. Here we performed yeast two-hybrid
      screens of 3,305 baits against 3,606 preys (~70% of the E. coli proteome) in
      duplicate to generate a map of 2,234 interactions, which approximately doubles
      the number of known binary PPIs in E. coli. Integration of binary PPI and genetic
      interaction data revealed functional dependencies among components involved in
      cellular processes, including envelope integrity, flagellum assembly and protein
      quality control. Many of the binary interactions that we could map in
      multiprotein complexes were informative regarding internal topology of complexes
      and indicated that interactions in complexes are substantially more conserved
      than those interactions connecting different complexes. This resource will be
      useful for inferring bacterial gene function and provides a draft reference of
      the basic physical wiring network of this evolutionarily important model microbe.

PMID- 24561555
TI  - Whole-genome haplotyping using long reads and statistical methods.
AB  - The rapid growth of sequencing technologies has greatly contributed to our
      understanding of human genetics. Yet, despite this growth, mainstream
      technologies have not been fully able to resolve the diploid nature of the human
      genome. Here we describe statistically aided, long-read haplotyping (SLRH), a
      rapid, accurate method that uses a statistical algorithm to take advantage of the
      partially phased information contained in long genomic fragments analyzed by
      short-read sequencing. For a human sample, as little as 30 Gbp of additional
      sequencing data are needed to phase genotypes identified by 50* coverage whole
      genome sequencing. Using SLRH, we phase 99% of single-nucleotide variants in
      three human genomes into long haplotype blocks 0.2-1 Mbp in length. We apply our
      method to determine allele-specific methylation patterns in a human genome and
      identify hundreds of differentially methylated regions that were previously
      unknown. SLRH should facilitate population-scale haplotyping of human genomes. 

PMID- 24561557
TI  - Chemosystematic identification of fifteen new cocaine-bearing Erythroxylum
      cultigens grown in Colombia for illicit cocaine production.
AB  - Colombian coca farmers have historically cultivated three varieties of coca for
      cocaine production (Erythroxylum novogranatense var. novogranatense, Erythroxylum
      novogranatense var. truxillense, and Erythroxylum coca var. ipadu). Within the
      past 13 years, 15 new cultigens of cocaine-bearing Erythroxylum have been
      propagated by Colombian coca farmers; each with differing physical
      characteristics, yet producing cocaine alkaloids at similar levels found in the
      historical and native varieties. Fifteen new cultigens were collected from
      throughout Colombia and propagated along with the three historical varieties
      within an experimental field in Colombia. Five plants/cultigen were randomly
      selected and examined for alkaloid content to determine their varietal
      characteristics when compared to the three known varieties. Ten cultigens gave
      classic Erythroxylum coca var. ipadu alkaloid profiles, four cultigens produced
      alkaloid profiles consistent with a hybridization of Erythroxylum novogranatense
      and Erythroxylum coca var. ipadu, while one cultigen gave heterogeneous alkaloid
      profiles that could not be characterized. 

PMID- 24561558
TI  - Behavioral genetics and criminal responsibility at the courtroom.
AB  - Several questions arise from the recent use of behavioral genetic research data
      in the courtroom. Ethical issues concerning the influence of biological factors
      on human free will, must be considered when specific gene patterns are advocated
      to constrain court's judgment, especially regarding violent crimes. Aggression
      genetics studies are both difficult to interpret and inconsistent, hence, in the
      absence of a psychiatric diagnosis, genetic data are currently difficult to
      prioritize in the courtroom. The judge's probabilistic considerations in
      formulating a sentence must take into account causality, and the latter cannot be
      currently ensured by genetic data. 

PMID- 24561556
TI  - Mesenchymal stem cells: immune evasive, not immune privileged.
AB  - The diverse immunomodulatory properties of mesenchymal stem/stromal cells (MSCs)
      may be exploited for treatment of a multitude of inflammatory conditions. MSCs
      have long been reported to be hypoimmunogenic or 'immune privileged'; this
      property is thought to enable MSC transplantation across major histocompatibility
      barriers and the creation of off-the-shelf therapies consisting of MSCs grown in
      culture. However, recent studies describing generation of antibodies against and
      immune rejection of allogeneic donor MSCs suggest that MSCs may not actually be
      immune privileged. Nevertheless, whether rejection of donor MSCs influences the
      efficacy of allogeneic MSC therapies is not known, and no definitive clinical
      advantage of autologous MSCs over allogeneic MSCs has been demonstrated to date.
      Although MSCs may exert therapeutic function through a brief 'hit and run'
      mechanism, protecting MSCs from immune detection and prolonging their persistence
      in vivo may improve clinical outcomes and prevent patient sensitization toward
      donor antigens. 

PMID- 24561560
TI  - Flux analysis in plant metabolic networks: increasing throughput and coverage.
AB  - Quantitative information about metabolic networks has been mainly obtained at the
      level of metabolite contents, transcript abundance, and enzyme activities.
      However, the active process of metabolism is represented by the flow of matter
      through the pathways. These metabolic fluxes can be predicted by Flux Balance
      Analysis or determined experimentally by (13)C-Metabolic Flux Analysis. These
      relatively complicated and time-consuming methods have recently seen significant
      improvements at the level of coverage and throughput. Metabolic models have
      developed from single cell models into whole-organism dynamic models. Advances in
      lab automation and data handling have significantly increased the throughput of
      flux measurements. This review summarizes advances to increase coverage and
      throughput of metabolic flux analysis in plants. 

PMID- 24561559
TI  - Characterization of ocular motor deficits in congenital facial weakness: Moebius
      and related syndromes.
AB  - Congenital facial weakness is present in a heterogeneous group of conditions.
      Among them is Moebius syndrome, which has been defined as a disorder with
      congenital, non-progressive facial weakness and limited abduction of one or both
      eyes. It is typically attributed to agenesis of the abducens and facial cranial
      nerves. This paper details ocular motor findings of 40 subjects (23 months to 64
      years; 24 females, 16 males) with congenital facial weakness: 38 presented at a
      Moebius Syndrome Conference and two were clinic patients. A new classification
      scheme of patterns based on ocular motor phenotype is presented. Of 40 subjects,
      37 had bilateral and three had unilateral facial weakness. The most common ocular
      motor pattern (Pattern 1, n=17, 43%) was bilateral horizontal gaze palsy with
      intact vertical range. Pattern 2 (n=10, 26%) was bilateral horizontal gaze palsy
      with variable vertical limitations. Pattern 3, which was rare, was isolated
      abduction deficits (n=2, 5%). Others had full motility range and did not meet
      minimal criteria for the diagnosis of Moebius syndrome (Pattern 4, n=10, 26%).
      One subject was too severely affected to characterize. Abnormal vertical smooth
      pursuit was present in 17 (57%) of 30 subjects: nine with Pattern 1, five with
      Pattern 2, and three with Pattern 4. Abnormal vertical saccades were present in
      10 (34%) of 29 subjects. Vertical saccades appeared slow in nine: six with
      Pattern 1 and three with Pattern 2. Vertical saccades were absent in one subject
      with Pattern 2. Abnormal vertical optokinetic nystagmus was present in 19 (68%)
      of 28 subjects: 10 with Pattern 1, six with Pattern 2, one with Pattern 3, and
      two with Pattern 4. Reduced convergence was present in 19 (66%) of 29 subjects:
      nine with Pattern 1, six with Pattern 2, one with Pattern 3, and three with
      Pattern 4. The most common pattern of ocular motor deficit in Moebius syndrome is
      bilateral horizontal gaze palsy from pontine abducens nuclear defects, rather
      than abducens nerve involvement. Defects in the range or dynamic properties of
      vertical movements in subjects with congenital facial weakness may suggest
      involvement of ocular motor structures in the midbrain, including oculomotor
      nerves or nuclei, vertical supranuclear saccadic centres, and convergence
      neurons. Such deficits were found even in subjects with full vertical motility
      range. Classification of patterns of ocular motor deficits in congenital facial
      weakness may assist with further delineation of anatomic localization and
      identification of genetic deficits underlying these disorders.

PMID- 24561561
TI  - Entropy and biological systems: experimentally-investigated entropy-driven
      stacking of plant photosynthetic membranes.
AB  - According to the Second Law of Thermodynamics, an overall increase of entropy
      contributes to the driving force for any physicochemical process, but entropy has
      seldom been investigated in biological systems. Here, for the first time, we
      apply Isothermal Titration Calorimetry (ITC) to investigate the Mg(2+)-induced
      spontaneous stacking of photosynthetic membranes isolated from spinach leaves.
      After subtracting a large endothermic interaction of MgCl2 with membranes,
      unrelated to stacking, we demonstrate that the enthalpy change (heat change at
      constant pressure) is zero or marginally positive or negative. This first direct
      experimental evidence strongly suggests that an entropy increase significantly
      drives membrane stacking in this ordered biological structure. Possible
      mechanisms for the entropy increase include: (i) the attraction between discrete
      oppositely-charged areas, releasing counterions; (ii) the release of loosely
      bound water molecules from the inter-membrane gap; (iii) the increased
      orientational freedom of previously-aligned water dipoles; and (iv) the lateral
      rearrangement of membrane components.

PMID- 24561562
TI  - Microcirculatory alterations in traumatic hemorrhagic shock.
AB  - OBJECTIVES: Microcirculatory dysfunction has been well reported in clinical
      studies in septic shock. However, no clinical studies have investigated
      microcirculatory blood flow behavior in hemorrhagic shock. The main objective of
      this study was to assess the time course of sublingual microcirculation in
      traumatic hemorrhagic shock during the first 4 days after trauma. DESIGN:
      Prospective observational study. SETTING ICU PATIENTS: Eighteen traumatic
      hemorrhagic shock patients. INTERVENTIONS: The sublingual microcirculation was
      estimated at the study inclusion after surgical or angiographic embolization to
      control bleeding (D1), and then three times at 24-hour intervals (D2, D3, and
      D4). MEASUREMENTS AND MAIN RESULTS: Sublingual microcirculation was impaired for
      72 hours despite restoration of the macrovascular circulation after control of
      bleeding in traumatic hemorrhagic shock patients. Furthermore, we found
      significantly higher decreases in the microvascular flow index and proportion of
      perfused vessels in high Sequential Organ Failure Assessment score patients at D4
      (Sequential Organ Failure Assessment score >= 6) compared to low Sequential Organ
      Failure Assessment score patients at D4 (Sequential Organ Failure Assessment
      score < 6) without any differences in global hemodynamics between these two
      groups. Finally, the initial proportion of perfused vessels at D1 appears to be a
      good predictor of high Sequential Organ Failure Assessment score at D4.
      CONCLUSIONS: Alterations of microcirculation in traumatic hemorrhagic shock
      patients result from the interplay among hemorrhage-induced tissue hypoperfusion,
      trauma injuries, inflammatory response, and subsequent resuscitation
      interventions. Despite restoration of the macrocirculation, the sublingual
      microcirculation was impaired for at least 72 hours. The initial proportion of
      perfused vessels appears to be a good predictor of high Sequential Organ Failure
      Assessment score at D4. Further studies are required to firmly establish the link
      between microvascular alterations and organ dysfunction in traumatic hemorrhagic
      shock patients.

PMID- 24561563
TI  - Early postresuscitation hypotension is associated with increased mortality
      following pediatric cardiac arrest.
AB  - OBJECTIVE: To describe the association of systolic hypotension during the first 6
      hours after successful resuscitation from pediatric cardiopulmonary arrest with
      in-hospital mortality. DESIGN: Retrospective cohort study. SETTING: Fifteen
      children's hospitals associated with the Pediatric Emergency Care Applied
      Research Network. PATIENTS: Patients between 1 day and 18 years old who had a
      cardiopulmonary arrest, received chest compressions more than 1 minute, had a
      return of spontaneous circulation more than 20 minutes, and had a systolic blood
      pressure documented within 6 hours of arrest. INTERVENTIONS: None. MEASUREMENTS
      AND MAIN RESULTS: Three hundred eighty-three patients had complete data for
      analysis. Patients with a documented minimum systolic blood pressure less than
      fifth percentile for age and sex within the first 6 hours following return of
      spontaneous circulation were considered to have early postresuscitation
      hypotension. Two hundred fourteen patients (56%) had early postresuscitation
      hypotension. One hundred eighty-four patients (48%) died prior to hospital
      discharge. After controlling for patient and cardiopulmonary arrest
      characteristics, hypotension in the first 6 hours following return of spontaneous
      circulation was associated with a significantly increased odds of in-hospital
      mortality (adjusted odds ratio = 1.71; 95% CI, 1.02-2.89; p = 0.042) and odds of
      unfavorable outcome (adjusted odds ratio = 1.83; 95% CI, 1.06-3.19; p = 0.032).
      CONCLUSIONS: In the first 6 hours following successful resuscitation from
      pediatric cardiac arrest, systolic hypotension was documented in 56% and was
      associated with a higher rate of in-hospital mortality and worse hospital
      discharge neurologic outcomes.

PMID- 24561564
TI  - Traumatic injury, early gene expression, and gram-negative bacteremia.
AB  - OBJECTIVES: Bacteremic trauma victims have a higher risk of death than their
      nonbacteremic counterparts. The role that altered immunity plays in the
      development of bacteremia is unknown. Using an existing dataset, we sought to
      determine if differences in early postinjury immune-related gene expression are
      associated with subsequent Gram-negative bacteremia. DESIGN: Retrospective cohort
      study, a secondary analysis of the Glue Grant database. SETTING: Seven level I
      trauma centers across the United State. SUBJECTS: Severely injured blunt trauma
      patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Total leukocyte
      gene expression was compared between the subjects in whom Gram-negative
      bacteremia developed and those in whom it did not develop. We observed that Gram
      negative bacteremia was an independent risk factor for death (odds ratio, 1.86; p
      = 0.015). We then compared gene expression at 12 and 96 hours after injury in 10
      subjects in whom subsequently Gram-negative bacteremia developed matched to 26
      subjects in whom it did not develop. At 12 hours, expression of 64 probes
      differed more than or equal to 1.5-fold; none represented genes related to innate
      or adaptive immunity. By 96 hours, 102 probes were differentially expressed with
      20 representing 15 innate or adaptive immunity genes, including down-regulation
      of IL1B and up-regulation of IL1R2, reflecting suppression of innate immunity in
      Gram-negative bacteremia subjects. We also observed down-regulation of adaptive
      immune genes in the Gram-negative bacteremia subjects. CONCLUSIONS: By 96 hours
      after injury, there are differences in leukocyte gene expression associated with
      the development of Gram-negative bacteremia, reflecting suppression of both
      innate and adaptive immunity. Gram-negative bacteremia after trauma is, in part,
      consequence of host immunity failure and may not be completely preventable by
      standard infection-control techniques.

PMID- 24561565
TI  - C1 esterase inhibitor activity in amniotic fluid embolism.
AB  - OBJECTIVES: Amniotic fluid embolism exhibits activation of the complement system
      and the kallikrein-kinin and coagulofibrinolytic systems. C1 esterase inhibitor
      is a major inhibitor of C1 esterase and can inhibit plasma kallikrein and also
      factors XIIa and XIa. Its activity has been shown to be significantly lower in
      pregnancy and labor than in the nonpregnant state. The purpose of this study was
      to determine C1 esterase inhibitor activity levels in amniotic fluid embolism.
      DESIGN: Retrospective study. SETTING: A single university-based center. PATIENTS:
      One hundred six cases with amniotic fluid embolism in a total of 194 singleton
      pregnant women between January 2010 and December 2011. INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: One hundred six cases of amniotic fluid embolism
      had applied to the Japan amniotic fluid embolism registration center in Hamamatsu
      University School of Medicine between January 2010 and December 2011. In amniotic
      fluid embolism cases, 85 cases were nonfatal and 21 cases were fatal. Eighty
      eight women who delivered without amniotic fluid embolism were regarded as a
      control. C1 esterase inhibitor activity levels were significantly lower in
      amniotic fluid embolism patients (30.0% +/- 1.8%) than in control women (62.0% +/
      2.0%) (p < 0.0001). C1 esterase inhibitor activity levels in fatal amniotic
      fluid embolism cases (22.5% +/- 3.4%) were significantly lower than those in
      nonfatal amniotic fluid embolism cases (32.0% +/- 2.1%) (p < 0.05). CONCLUSIONS:
      These results demonstrated that low C1 esterase inhibitor activity levels were
      closely associated with the pathogenesis of amniotic fluid embolism suggesting
      that C1 esterase inhibitor activity levels have potential as a prognosis factor
      of amniotic fluid embolism.

PMID- 24561566
TI  - Conservative oxygen therapy in mechanically ventilated patients: a pilot before
      and-after trial.
AB  - OBJECTIVES: To assess the feasibility and safety of a conservative approach to
      oxygen therapy in mechanically ventilated ICU patients. DESIGN: Pilot prospective
      before-and-after study. SETTING: A 22-bed multidisciplinary ICU of a tertiary
      care hospital in Australia. PATIENTS: A total of 105 adult (18 years old or
      older) patients required mechanical ventilation for more than 48 hours: 51
      patients during the "conventional" before period and 54 after a change to
      "conservative" oxygen therapy. INTERVENTIONS: Implementation of a conservative
      approach to oxygen therapy (target SpO2 of 90-92%). MEASUREMENTS AND MAIN
      RESULTS: We collected 3,169 datasets on 799 mechanical ventilation days. During
      conservative oxygen therapy the median time-weighted average SpO2 on mechanical
      ventilation was 95.5% (interquartile range, 94.0-97.3) versus 98.4% (97.3-99.1)
      (p < 0.001) during conventional therapy. The median PaO2 was 83 torr (71-94)
      versus 107 torr (94-131) (p < 0.001) with a change to a median FIO2 of 0.27 (0.24
      0.30) versus 0.40 (0.35-0.44) (p < 0.001). Conservative oxygen therapy decreased
      the median total amount of oxygen delivered during mechanical ventilation by
      about two thirds (15,580 L [8,263-29,351 L] vs 5,122 L [1,837-10,499 L]; p <
      0.001). The evolution of the PaO2/FIO2 ratio was similar during the two periods,
      and there were no difference in any other biochemical or clinical outcomes.
      CONCLUSIONS: Conservative oxygen therapy in mechanically ventilated ICU patients
      was feasible and free of adverse biochemical, physiological, or clinical outcomes
      while allowing a marked decrease in excess oxygen exposure. Our study supports
      the safety and feasibility of future pilot randomized controlled trials of
      conventional compared with conservative oxygen therapy.

PMID- 24561567
TI  - Stress hyperlactatemia modifies the relationship between stress hyperglycemia and
      outcome: a retrospective observational study.
AB  - OBJECTIVE: To study the effect of stress hyperlactatemia on the association
      between stress hyperglycemia and mortality. DESIGN: Retrospective cross-sectional
      observation study. SETTING: Three ICUs using arterial blood gases with
      simultaneous glucose and lactate measurements during ICU stay. PATIENTS: Cohort
      of 7,925 consecutive critically ill patients. INTERVENTIONS: None. MEASUREMENTS
      AND MAIN RESULTS: We analyzed 152,349 simultaneous measurements of glucose and
      lactate. We performed multivariable analysis to study the association of
      different metrics of glucose and lactate with hospital mortality. On day 1, first
      (p = 0.013), highest (p = 0.001), mean (p = 0.019), and time-weighted mean (p =
      0.010) glucose levels were associated with increased mortality. A similar, but
      stronger, association was seen for corresponding lactate metrics (p < 0.0001 for
      all). However, once glucose and lactate metrics were entered into the
      multivariable logistic regression model simultaneously, all measures of glycemia
      ceased to be significantly associated with hospital mortality regardless of the
      metrics being used (first, highest, mean, time-weighed; p > 0.05 for all),
      whereas all lactate metrics remained associated with mortality (p < 0.0001 for
      all). In patients with at least one episode of moderate hypoglycemia (glucose <=
      3.9 mmol/L), glucose metrics were not associated with mortality when studied
      separately (p > 0.05 for all), whereas lactate was (p < 0.05 for all), but when
      incorporated into a model simultaneously, highest glucose on day 1 was associated
      with mortality (p< 0.05), but not other glucose metrics (p > 0.05), whereas all
      lactate metrics remained associated with mortality (p < 0.05 for all).
      CONCLUSIONS: Stress hyperlactatemia modifies the relationship between
      hyperglycemia and mortality. There is no independent association between
      hyperglycemia and mortality once lactate levels are considered.

PMID- 24561568
TI  - Cross-sectional changes in lung volume measured by electrical impedance
      tomography are representative for the whole lung in ventilated preterm infants.
AB  - OBJECTIVE: Electrical impedance tomography measures lung volume in a cross
      sectional slice of the lung. Whether these cross-sectional volume changes are
      representative of the whole lung has only been investigated in adults, showing
      conflicting results. This study aimed to compare cross-sectional and whole lung
      volume changes using electrical impedance tomography and respiratory inductive
      plethysmography. DESIGN: A prospective, single-center, observational,
      nonrandomized study. SETTING: The study was conducted in a neonatal ICU in the
      Netherlands. PATIENTS: High-frequency ventilated preterm infants with respiratory
      distress syndrome. INTERVENTIONS: Cross-sectional and whole lung volume changes
      were continuously and simultaneously measured by, respectively, electrical
      impedance tomography and respiratory inductive plethysmography during a stepwise
      recruitment procedure. End-expiratory lung volume changes were assessed by
      mapping the inflation and deflation limbs using both the pressure/impedance and
      pressure/inductance pairs and characterized by calculating the inflection points.
      In addition, oscillatory tidal volume changes were assessed at each pressure
      step. MEASUREMENTS AND MAIN RESULTS: Twenty-three infants were included in the
      study. Of these, eight infants had to be excluded because the quality of the
      registration was insufficient for analysis (two electrical impedance tomography
      and six respiratory inductive plethysmography). In the remaining 15 infants
      (gestational age 28.0 +/- 2.6 wk; birth weight 1,027 +/- 514 g), end-expiratory
      lung volume changes measured by electrical impedance tomography were
      significantly correlated to respiratory inductive plethysmography measurements in
      12 patients (mean r = 0.93 +/- 0.05). This was also true for the upper inflection
      point on the inflation (r = 0.91, p < 0.01) and deflation limb (r = 0.83, p <
      0.01). In 13 patients, impedance and inductance data also correlated
      significantly on oscillatory tidal volume/pressure relationships (mean r = 0.81
      +/- 0.18). CONCLUSIONS: This study shows that cross-sectional lung volume changes
      measured by electrical impedance tomography are representative for the whole lung
      and that this concept also applies to newborn infants.

PMID- 24561569
TI  - Is selective antegrade cerebral perfusion superior to retrograde cerebral
      perfusion for brain protection during deep hypothermic circulatory arrest?
      Metabolic evidence from microdialysis.
AB  - OBJECTIVES: This study aimed to investigate whether selective antegrade cerebral
      perfusion or retrograde cerebral perfusion is a better technique for brain
      protection in deep hypothermic circulatory arrest by obtaining metabolic evidence
      from microdialysis. DESIGN: Randomized, animal study. SETTING: Assisted
      circulation laboratory. SUBJECTS: Eighteen piglets of either sex (9.8 +/- 3.1
      kg). INTERVENTIONS: Animals were randomly assigned to 40 minutes of circulatory
      arrest at 18 degrees C without cerebral perfusion (deep hypothermic circulatory
      arrest group, n = 6) or with selective antegrade cerebral perfusion (selective
      antegrade cerebral perfusion group, n = 6) or retrograde cerebral perfusion
      (retrograde cerebral perfusion group, n = 6). Reperfusion was continued for 3
      hours. MEASUREMENTS AND MAIN RESULTS: Microdialysis (glucose, lactate, pyruvate,
      and glycerol) variables in the cortex dialysate were measured every 30 minutes.
      Intracerebral pressure and serum S-100 levels were also monitored. After 3 hours
      of reperfusion, cortical tissue was harvested for terminal deoxynucleotidyl
      transferase dUTP nick-end labeling staining. After 40 minutes of circulatory
      arrest, the deep hypothermic circulatory arrest group presented marked elevations
      of intracerebral pressure, and serum S-100 levels were higher in the deep
      hypothermic circulatory arrest group than in the other two groups (p < 0.001,
      respectively). The selective antegrade cerebral perfusion group exhibited higher
      glucose, lower lactate, and lower glycerol levels and a lower lactate-to-pyruvate
      ratio in comparison to the deep hypothermic circulatory arrest group (p < 0.05,
      respectively); the retrograde cerebral perfusion group had lower lactate and
      glycerol levels and a lower lactate-to-pyruvate ratio (p < 0.05, respectively)
      but similar glucose levels compared to deep hypothermic circulatory arrest alone.
      Furthermore, selective antegrade cerebral perfusion provided better preservation
      of energy and cell integrity than retrograde cerebral perfusion with higher
      glucose and lower glycerol levels (p < 0.05, respectively). After 3 hours of
      reperfusion, fewer apoptotic neurons were found in selective antegrade cerebral
      perfusion animals than in the other two groups (p < 0.05, respectively).
      CONCLUSIONS: Both selective antegrade cerebral perfusion and retrograde cerebral
      perfusion were superior to deep hypothermic circulatory arrest alone during
      circulatory arrest. Retrograde cerebral perfusion was a moderate technique that
      had similar advantages with regard to less cerebral edema, better clearance of
      metabolic waste, and lower levels of biomarkers of injury than selective
      antegrade cerebral perfusion, but its capacity for energy preservation,
      maintenance of cellular integrity, and protection against apoptosis was lower
      than that of selective antegrade cerebral perfusion.

PMID- 24561570
TI  - Benefits of optimising coronary flow before stenting in primary percutaneous
      coronary intervention for ST-elevation myocardial infarction: insights from
      INFUSE-AMI.
AB  - AIMS: To determine the relation between thrombus aspiration (TA) and/or intra
      lesion (IL) abciximab with pre-stent Thrombolysis In Myocardial Infarction (TIMI)
      flow grade and infarct size (IS) in patients with ST-elevation myocardial
      infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI).
      METHODS AND RESULTS: The INFUSE-AMI trial randomised 452 patients with anterior
      STEMI to IL abciximab vs. no abciximab, and to manual TA vs. no TA. The primary
      endpoint was cMRI-determined IS at 30 days. Patients were classified according to
      pre-stent TIMI flow. Complete data were available in 290 patients - 68 (25.2%)
      with pre-stent TIMI 0/1 flow, 47 (17.4%) with TIMI 2 flow and 175 (57.4%) with
      TIMI 3 flow. Patients with pre-stent TIMI 3 flow had significantly lower IS
      (15.5% [4.6, 21.8] vs. 22.6% [14.7, 28.0] for TIMI 2 vs. 19.5 [14.4, 27.8] for
      TIMI 0/1, p<0.0001) and fewer 30-day clinical events (p=0.03). Patients receiving
      TA with or without IL abciximab had the highest rate of pre-stent TIMI 3 flow
      (p<0.0001) and patients receiving both had the smallest IS (14.7% vs. 17.3% for
      the other three groups, p=0.03). CONCLUSIONS: Optimisation of coronary flow prior
      to stent implantation may reduce infarct size and clinical events in STEMI
      patients undergoing primary PCI.

PMID- 24561571
TI  - The mitochondrial respiratory chain of the secondary green alga Euglena gracilis
      shares many additional subunits with parasitic Trypanosomatidae.
AB  - The mitochondrion is an essential organelle for the production of cellular ATP in
      most eukaryotic cells. It is extensively studied, including in parasitic
      organisms such as trypanosomes, as a potential therapeutic target. Recently,
      numerous additional subunits of the respiratory-chain complexes have been
      described in Trypanosoma brucei and Trypanosoma cruzi. Since these subunits had
      apparently no counterparts in other organisms, they were interpreted as
      potentially associated with the parasitic trypanosome lifestyle. Here we used two
      complementary approaches to characterise the subunit composition of respiratory
      complexes in Euglena gracilis, a non-parasitic secondary green alga related to
      trypanosomes. First, we developed a phylogenetic pipeline aimed at mining
      sequence databases for identifying homologues to known respiratory-complex
      subunits with high confidence. Second, we used MS/MS proteomics after two
      dimensional separation of the respiratory complexes by Blue Native- and SDS-PAGE
      both to confirm in silico predictions and to identify further additional
      subunits. Altogether, we identified 41 subunits that are restricted to E.
      gracilis, T. brucei and T. cruzi, along with 48 classical subunits described in
      other eukaryotes (i.e. plants, mammals and fungi). This moreover demonstrates
      that at least half of the subunits recently reported in T. brucei and T. cruzi
      are actually not specific to Trypanosomatidae, but extend at least to other
      Euglenozoa, and that their origin and function are thus not specifically
      associated with the parasitic lifestyle. Furthermore, preliminary biochemical
      analyses suggest that some of these additional subunits underlie the
      peculiarities of the respiratory chain observed in Euglenozoa. 

PMID- 24561572
TI  - In vitro import and assembly of the nucleus-encoded mitochondrial subunit III of
      cytochrome c oxidase (Cox3).
AB  - The cox3 gene, encoding subunit III of cytochrome c oxidase (Cox3) is in
      mitochondrial genomes except in chlorophycean algae, where it is localized in the
      nucleus. Therefore, algae like Chlamydomonas reinhardtii, Polytomella sp. and
      Volvox carteri, synthesize the Cox3 polypeptide in the cytosol, import it into
      mitochondria, and integrate it into the cytochrome c oxidase complex. In this
      work, we followed the in vitro internalization of the Cox3 precursor by isolated,
      import-competent mitochondria of Polytomella sp. In this colorless alga, the
      precursor Cox3 protein is synthesized with a long, cleavable, N-terminal
      mitochondrial targeting sequence (MTS) of 98 residues. In an import time course,
      a transient Cox3 intermediate was identified, suggesting that the long MTS is
      processed more than once. The first processing step is sensitive to the metalo
      protease inhibitor 1,10-ortophenantroline, suggesting that it is probably carried
      out by the matrix-located Mitochondrial Processing Protease. Cox3 is readily
      imported through an energy-dependent import pathway and integrated into the inner
      mitochondrial membrane, becoming resistant to carbonate extraction. Furthermore,
      the imported Cox3 protein was assembled into cytochrome c oxidase, as judged by
      the presence of a labeled band co-migrating with complex IV in Blue Native
      Electrophoresis. A model for the biogenesis of Cox3 in chlorophycean algae is
      proposed. This is the first time that the in vitro mitochondrial import of a
      cytosol-synthesized Cox3 subunit is described. 

PMID- 24561573
TI  - The life of plant mitochondrial complex I.
AB  - The mitochondrial NADH dehydrogenase complex (complex I) of the respiratory chain
      has several remarkable features in plants: (i) particularly many of its subunits
      are encoded by the mitochondrial genome, (ii) its mitochondrial transcripts
      undergo extensive maturation processes (e.g. RNA editing, trans-splicing), (iii)
      its assembly follows unique routes, (iv) it includes an additional functional
      domain which contains carbonic anhydrases and (v) it is, indirectly, involved in
      photosynthesis. Comprising about 50 distinct protein subunits, complex I of
      plants is very large. However, an even larger number of proteins are required to
      synthesize these subunits and assemble the enzyme complex. This review aims to
      follow the complete "life cycle" of plant complex I from various molecular
      perspectives. We provide arguments that complex I represents an ideal model
      system for studying the interplay of respiration and photosynthesis, the
      cooperation of mitochondria and the nucleus during organelle biogenesis and the
      evolution of the mitochondrial oxidative phosphorylation system. 

PMID- 24561574
TI  - DNA-binding proteins in plant mitochondria: implications for transcription.
AB  - The structural complexity of plant mitochondrial genomes correlates with the
      variety of single-strand DNA-binding proteins found in plant mitochondria. Most
      of these are plant-specific and have roles in homologous recombination and genome
      maintenance. Mitochondrial nucleoids thus differ fundamentally between plants and
      yeast or animals, where the principal nucleoid protein is a DNA-packaging protein
      that binds double-stranded DNA. Major transcriptional cofactors identified in
      mitochondria of non-plant species are also seemingly absent from plants. This
      article reviews current knowledge on plant mitochondrial DNA-binding proteins and
      discusses that those may affect the accessibility and conformation of
      transcription start sites, thus functioning as transcriptional modulators without
      being dedicated transcription factors. 

PMID- 24561575
TI  - Mitochondrial 2-hydroxyglutarate metabolism.
AB  - 2-Hydroxyglutarate (2-HG) is a five-carbon dicarboxylic acid with a hydroxyl
      group at the alpha position, which forms a stereocenter in this molecule.
      Although the existence of mitochondrial D- and L-2HG metabolisms has long been
      known in different eukaryotes, the biosynthetic pathways, especially in plants,
      have not been completely elucidated. While D-2HG is involved in intermediary
      metabolism, L-2HG may not have a cellular function but it needs to be recycled
      through a metabolic repair reaction. Independent of their metabolic origin, D-
      and L-2HG are oxidized in plant mitochondria to 2-ketoglutarate through the
      action of two stereospecific enzymes, D- and L-2-hydroxyacid dehydrogenases.
      While plants are to a large extent unaffected by high cellular concentrations of
      D-2HG, deficiencies in the metabolism of D- and L-2HG result in fatal disorders
      in humans. We present current data gathered on plant D- and L-2HG metabolisms and
      relate it to existing knowledge on 2HG metabolism in other organisms. We focus on
      the metabolic origin of these compounds, the mitochondrial catabolic steps
      catalyzed by the stereospecific dehydrogenases, and phylogenetic relationships
      between different studied 2-hydroxyacid dehydrogenases.

PMID- 24561576
TI  - Photophysical and excited-state intramolecular proton transfer of 2-(1-(3,5
      dimethylphenyl)-1H-phenanthro[9,10-d]imidazol-2-yl)phenol: DFT analysis.
AB  - Fluorescent phenenthrimidazole derivatives have been synthesized and
      characterized by (1)H, (13)C NMR and mass spectral analyses. Synthesized
      compounds have been. The solvent effect on the absorption and fluorescence bands
      has been analyzed and supplement by computational studies. Phenenthrimidazole
      containing hydroxy group shows a single prominent absorption and emission in
      polar solvents and dual emission in non-polar solvents due to excited state
      intramolecular proton transfer (ESIPT). The ESIPT of 2-(1-(3,5-dimethylphenyl)-1H
      phenanthro[9,10-d]imidazol-2-yl)phenol was cross validated by the analysis of
      optimized geometry parameters, potential energy surface (PES), mulliken's charge
      distribution on the heavy atoms and molecular orbitals of its tautomers.
      Nonviability of ground state electron transfer was explained by HOMO-LUMO
      analysis. The intramolecular hydrogen bonding (IMHB) interaction has been
      explored by the calculation of electron density rho(r) and the Laplacian
      Delta(2)rho(r) at the bond critical point (BCP) using atoms-in-molecule (AIM)
      method and by calculation of hyper conjugative interaction between N17 lone pair
      and sigma*(O53?H54) using natural bond orbital (NBO) analysis.

PMID- 24561577
TI  - Rapid reaction of superoxide with insulin-tyrosyl radicals to generate a
      hydroperoxide with subsequent glutathione addition.
AB  - Tyrosine (Tyr) residues are major sites of radical generation during protein
      oxidation. We used insulin as a model to study the kinetics, mechanisms, and
      products of the reactions of radiation-induced or enzyme-generated protein
      tyrosyl radicals with superoxide to demonstrate the feasibility of these
      reactions under oxidative stress conditions. We found that insulin-tyrosyl
      radicals combined to form dimers, mostly via the tyrosine at position 14 on the
      alpha chain (Tyr14). However, in the presence of superoxide, dimerization was
      largely outcompeted by the reaction of superoxide with insulin-tyrosyl radicals.
      Using pulse radiolysis, we measured a second-order rate constant for the latter
      reaction of (6+/-1) * 10(8) M(-1) s(-1) at pH 7.3, representing the first
      measured rate constant for a protein-tyrosyl radical with superoxide. Mass
      spectrometry-based product analyses revealed the addition of superoxide to the
      insulin-Tyr14 radical to form the hydroperoxide. Glutathione efficiently reduced
      the hydroperoxide to the corresponding monoxide and also subsequently underwent
      Michael addition to the monoxide to give a diglutathionylated protein adduct.
      Although much slower, conjugation of the backbone amide group can form a bicyclic
      Tyr-monoxide derivative, allowing the addition of only one glutathione molecule.
      These findings suggest that Tyr-hydroperoxides should readily form on proteins
      under oxidative stress conditions where protein radicals and superoxide are both
      generated and that these should form addition products with thiol compounds such
      as glutathione.

PMID- 24561578
TI  - OxLDL induces endothelial dysfunction and death via TRAF3IP2: inhibition by HDL3
      and AMPK activators.
AB  - Oxidized low-density lipoprotein (oxLDL) induces endothelial cell death through
      the activation of NF-kappaB and AP-1 pathways. TRAF3IP2 is a redox-sensitive
      cytoplasmic adapter protein and an upstream regulator of IKK/NF-kappaB and JNK/AP
      1. Here we show that oxLDL-induced death in human primary coronary artery
      endothelial cells (ECs) was markedly attenuated by the knockdown of TRAF3IP2 or
      the lectin-like oxLDL receptor 1 (LOX-1). Further, oxLDL induced Nox2/superoxide
      dependent TRAF3IP2 expression, IKK/p65 and JNK/c-Jun activation, and LOX-1
      upregulation, suggesting a reinforcing mechanism. Similarly, the lysolipids
      present in oxLDL (16:0-LPC and 18:0-LPC) and minimally modified LDL also
      upregulated TRAF3IP2 expression. Notably, whereas native HDL3 reversed oxLDL
      induced TRAF3IP2 expression and cell death, 15-lipoxygenase-modified HDL3
      potentiated its proapoptotic effects. The activators of the AMPK/Akt pathway,
      adiponectin, AICAR, and metformin, attenuated superoxide generation, TRAF3IP2
      expression, and oxLDL/TRAF3IP2-mediated EC death. Further, both HDL3 and
      adiponectin reversed oxLDL/TRAF3IP2-dependent monocyte adhesion to endothelial
      cells in vitro. Importantly, TRAF3IP2 gene deletion and the AMPK activators
      reversed oxLDL-induced impaired vasorelaxation ex vivo. These results indicate
      that oxLDL-induced endothelial cell death and dysfunction are mediated via
      TRAF3IP2 and that native HDL3 and the AMPK activators inhibit this response.
      Targeting TRAF3IP2 could potentially inhibit progression of atherosclerotic
      vascular diseases. 

PMID- 24561579
TI  - 4-Hydroxynonenal impairs transforming growth factor-beta1-induced elastin
      synthesis via epidermal growth factor receptor activation in human and murine
      fibroblasts.
AB  - Elastin is a long-lived protein and a key component of connective tissues. The
      tissular elastin content decreases during chronological aging, and the mechanisms
      underlying its slow repair are not known. Lipid oxidation products that
      accumulate in aged tissues may generate protein dysfunction. We hypothesized that
      4-hydroxynonenal (4-HNE), a highly reactive alpha,beta-aldehydic product
      generated from polyunsaturated fatty acid peroxidation, could contribute to
      inhibiting elastin repair by antagonizing the elastogenic signaling of
      transforming growth factor-beta1 (TGF-beta1) in skin fibroblasts. We report that
      a low 4-HNE concentration (2umol/L) inhibits the upregulation of tropoelastin
      expression stimulated by TGF-beta1 in human and murine fibroblasts. The study of
      signaling pathways potentially involved in the regulation of elastin expression
      showed that 4-HNE did not block the phosphorylation of Smad3, an early step of
      TGF-beta1 signaling, but inhibited the nuclear translocation of Smad2.
      Concomitantly, 4-HNE modified and stimulated the phosphorylation of the epidermal
      growth factor receptor (EGFR) and subsequently ERK1/2 activation, leading to the
      phosphorylation/stabilization of the Smad transcriptional corepressor TGIF, which
      antagonizes TGF-beta1 signaling. Inhibitors of EGFR (AG1478) and MEK/ERK
      (PD98059), and EGFR-specific siRNAs, reversed the inhibitory effect of 4-HNE on
      TGF-beta1-induced nuclear translocation of Smad2 and tropoelastin synthesis. In
      vivo studies on aortas from aged C57BL/6 mice showed that EGFR is modified by 4
      HNE, in correlation with an increased 4-HNE-adduct accumulation and decreased
      elastin content. Altogether, these data suggest that 4-HNE inhibits the
      elastogenic activity of TGF-beta1, by modifying and activating the EGFR/ERK/TGIF
      pathway, which may contribute to altering elastin repair in chronological aging
      and oxidative stress-associated aging processes. 

PMID- 24561580
TI  - Evaluation of cytotoxic effects of 7-dehydrocholesterol on melanoma cells.
AB  - Ultraviolet radiation is the main cause of skin cancers, and melanoma is the most
      serious form of tumor. There is no therapy for advanced-stage melanoma and its
      metastasis because of their high resistance to various anticancer therapies.
      Human skin is an important metabolic organ in which occurs photoinduced synthesis
      of vitamin D3 from 7-dehydrocholesterol (7-DHC). 7-DHC, the precursor of
      cholesterol biosynthesis, is highly reactive and easily modifiable to produce 7
      DHC-derived compounds. The intracellular levels of 7-DHC or its derivatives can
      have deleterious effects on cellular functionality and viability. In this study
      we evaluated the effects on melanoma cell lines of 7-DHC as such and for this aim
      we used much care to minimize 7-DHC modifications. We found that from 12 to 72 h
      of treatment 82-86% of 7-DHC entered the cells, and the levels of 7-DHC-derived
      compounds were not significant. Simultaneously, reactive oxygen species
      production was significantly increased already after 2h. After 24 h and up to 72
      h, 7-DHC-treated melanoma cells showed a reduction in cell growth and viability.
      The cytotoxic effect of 7-DHC was associated with an increase in Bax levels,
      decrease in Bcl-2/Bax ratio, reduction of mitochondrial membrane potential,
      increase in apoptosis-inducing factor levels, unchanged caspase-3 activity, and
      absence of cleavage of PARP-1. These findings could explain the mechanism through
      which 7-DHC exerts its cytotoxic effects. This is the first report in which the
      biological effects found in melanoma cells are mainly attributable to 7-DHC as
      such.

PMID- 24561581
TI  - The lipopeptide antibiotic paenibacterin binds to the bacterial outer membrane
      and exerts bactericidal activity through cytoplasmic membrane damage.
AB  - Paenibacterin is a broad-spectrum lipopeptide antimicrobial agent produced by
      Paenibacillus thiaminolyticus OSY-SE. The compound consists of a cyclic 13
      residue peptide and an N-terminal C15 fatty acyl chain. The mechanism of action
      of paenibacterin against Escherichia coli and Staphylococcus aureus was
      investigated in this study. The cationic lipopeptide paenibacterin showed a
      strong affinity for the negatively charged lipopolysaccharides (LPS) from the
      outer membrane of Gram-negative bacteria. Addition of LPS (100 MUg/ml) completely
      eliminated the antimicrobial activity of paenibacterin against E. coli. The
      electrostatic interaction between paenibacterin and LPS may have displaced the
      divalent cations on the LPS network and thus facilitated the uptake of antibiotic
      into Gram-negative cells. Paenibacterin also damaged the bacterial cytoplasmic
      membrane, as evidenced by the depolarization of membrane potential and leakage of
      intracellular potassium ions from cells of E. coli and S. aureus. Therefore, the
      bactericidal activity of paenibacterin is attributed to disruption of the outer
      membrane of Gram-negative bacteria and damage of the cytoplasmic membrane of both
      Gram-negative and Gram-positive bacteria. Despite the evidence of membrane
      damage, this study does not rule out additional bactericidal mechanisms
      potentially exerted by paenibacterin. 

PMID- 24561582
TI  - Superoxide production by a manganese-oxidizing bacterium facilitates iodide
      oxidation.
AB  - The release of radioactive iodine (i.e., iodine-129 and iodine-131) from nuclear
      reprocessing facilities is a potential threat to human health. The fate and
      transport of iodine are determined primarily by its redox status, but processes
      that affect iodine oxidation states in the environment are poorly characterized.
      Given the difficulty in removing electrons from iodide (I(-)), naturally
      occurring iodide oxidation processes require strong oxidants, such as Mn oxides
      or microbial enzymes. In this study, we examine iodide oxidation by a marine
      bacterium, Roseobacter sp. AzwK-3b, which promotes Mn(II) oxidation by catalyzing
      the production of extracellular superoxide (O2(-)). In the absence of Mn(2+),
      Roseobacter sp. AzwK-3b cultures oxidized ~90% of the provided iodide (10 MUM)
      within 6 days, whereas in the presence of Mn(II), iodide oxidation occurred only
      after Mn(IV) formation ceased. Iodide oxidation was not observed during
      incubations in spent medium or with whole cells under anaerobic conditions or
      following heat treatment (boiling). Furthermore, iodide oxidation was
      significantly inhibited in the presence of superoxide dismutase and diphenylene
      iodonium (a general inhibitor of NADH oxidoreductases). In contrast, the addition
      of exogenous NADH enhanced iodide oxidation. Taken together, the results indicate
      that iodide oxidation was mediated primarily by extracellular superoxide
      generated by Roseobacter sp. AzwK-3b and not by the Mn oxides formed by this
      organism. Considering that extracellular superoxide formation is a widespread
      phenomenon among marine and terrestrial bacteria, this could represent an
      important pathway for iodide oxidation in some environments. 

PMID- 24561583
TI  - Performance and specificity of the covalently linked immunomagnetic separation
      ATP method for rapid detection and enumeration of enterococci in coastal
      environments.
AB  - The performance and specificity of the covalently linked immunomagnetic
      separation-ATP (Cov-IMS/ATP) method for the detection and enumeration of
      enterococci was evaluated in recreational waters. Cov-IMS/ATP performance was
      compared with standard methods: defined substrate technology (Enterolert; IDEXX
      Laboratories), membrane filtration (EPA Method 1600), and an Enterococcus
      specific quantitative PCR (qPCR) assay (EPA Method A). We extend previous studies
      by (i) analyzing the stability of the relationship between the Cov-IMS/ATP method
      and culture-based methods at different field sites, (ii) evaluating specificity
      of the assay for seven ATCC Enterococcus species, (iii) identifying cross
      reacting organisms binding the antibody-bead complexes with 16S rRNA gene
      sequencing and evaluating specificity of the assay to five nonenterococcus
      species, and (iv) conducting preliminary tests of preabsorption as a means of
      improving the assay. Cov-IMS/ATP was found to perform consistently and with
      strong agreement rates (based on exceedance/compliance with regulatory limits) of
      between 83% and 100% compared to the culture-based Enterolert method at a variety
      of sites with complex inputs. The Cov-IMS/ATP method is specific to five of seven
      different Enterococcus spp. tested. However, there is potential for nontarget
      bacteria to bind the antibody, which may be reduced by purification of the IgG
      serum with preabsorption at problematic sites. The findings of this study help to
      validate the Cov-IMS/ATP method, suggesting a predictable relationship between
      the Cov-IMS/ATP method and traditional culture-based methods, which will allow
      for more widespread application of this rapid and field-portable method for
      coastal water quality assessment. 

PMID- 24561584
TI  - Bioconversion of pinoresinol into matairesinol by use of recombinant Escherichia
      coli.
AB  - Lignans, a class of dimeric phenylpropanoid derivative found in plants, such as
      whole grains and sesame and flax seeds, have anticancer activity and can act as
      phytoestrogens. The lignans secoisolariciresinol and matairesinol can be
      converted in the mammalian proximal colon into enterolactone and enterodiol,
      respectively, which reduce the risk of breast and colon cancer. To establish an
      efficient bioconversion system to generate matairesinol from pinoresinol, the
      genes encoding pinoresinol-lariciresinol reductase (PLR) and secoisolariciresinol
      dehydrogenase (SDH) were cloned from Podophyllum pleianthum Hance, an endangered
      herb in Taiwan, and the recombinant proteins, rPLR and rSDH, were expressed in
      Escherichia coli and purified. The two genes, termed plr-PpH and sdh-PpH, were
      also linked to form two bifunctional fusion genes, plr-sdh and sdh-plr, which
      were also expressed in E. coli and purified. Bioconversion in vitro at 22 degrees
      C for 60 min showed that the conversion efficiency of fusion protein PLR-SDH was
      higher than that of the mixture of rPLR and rSDH. The percent conversion of (+)
      pinoresinol to matairesinol was 49.8% using PLR-SDH and only 17.7% using a
      mixture of rPLR and rSDH. However, conversion of (+)-pinoresinol by fusion
      protein SDH-PLR stopped at the intermediate product, secoisolariciresinol. In
      vivo, (+)-pinoresinol was completely converted to matairesinol by living
      recombinant E. coli expressing PLR-SDH without addition of cofactors. 

PMID- 24561586
TI  - Effect of C-terminal protein tags on pentitol and L-arabinose transport by
      Ambrosiozyma monospora Lat1 and Lat2 transporters in Saccharomyces cerevisiae.
AB  - Functional expression in heterologous hosts is often less successful for integral
      membrane proteins than for soluble proteins. Here, two Ambrosiozyma monospora
      transporters were successfully expressed in Saccharomyces cerevisiae as tagged
      proteins. Growth of A. monospora on l-arabinose instead of glucose caused
      transport activities of l-arabinose, l-arabitol, and ribitol, measured using l-[1
      (3)H]arabinose, l-[(14)C]arabitol, and [(14)C]ribitol of demonstrated purity. A.
      monospora LAT1 and LAT2 genes were cloned earlier by using their ability to
      improve the growth of genetically engineered Saccharomyces cerevisiae on l
      arabinose. However, the l-arabinose and pentitol transport activities of S.
      cerevisiae carrying LAT1 or LAT2 are only slightly greater than those of control
      strains. S. cerevisiae carrying the LAT1 or LAT2 gene fused in frame to the genes
      for green fluorescent protein (GFP) or red fluorescent protein (mCherry) or
      adenylate kinase (AK) exhibited large (>3-fold for LAT1; >20-fold for LAT2)
      increases in transport activities. Lat1-mCherry transported l-arabinose with high
      affinity (Km ~ 0.03 mM) and l-arabitol and ribitol with very low affinity (Km >=
      75 mM). The Lat2-GFP, Lat2-mCherry, and Lat2-AK fusion proteins could not
      transport l-arabinose but were high-affinity pentitol transporters (Kms ~ 0.2
      mM). The l-arabinose and pentitol transport activities of A. monospora could not
      be completely explained by any combination of the observed properties of tagged
      Lat1 and Lat2, suggesting either that tagging and expression in a foreign
      membrane alters the transport kinetics of Lat1 and/or Lat2 or that A. monospora
      contains at least one more l-arabinose transporter.

PMID- 24561587
TI  - Predicting the concentration of verotoxin-producing Escherichia coli bacteria
      during processing and storage of fermented raw-meat sausages.
AB  - A model to predict the population density of verotoxigenic Escherichia coli
      (VTEC) throughout the elaboration and storage of fermented raw-meat sausages
      (FRMS) was developed. Probabilistic and kinetic measurement data sets collected
      from publicly available resources were completed with new measurements when
      required and used to quantify the dependence of VTEC growth and inactivation on
      the temperature, pH, water activity (aw), and concentration of lactic acid.
      Predictions were compared with observations in VTEC-contaminated FRMS
      manufactured in a pilot plant. Slight differences in the reduction of VTEC were
      predicted according to the fermentation temperature, 24 or 34 degrees C, with
      greater inactivation at the highest temperature. The greatest reduction was
      observed during storage at high temperatures. A population decrease greater than
      6 decimal logarithmic units was observed after 66 days of storage at 25 degrees
      C, while a reduction of only ca. 1 logarithmic unit was detected at 12 degrees C.
      The performance of our model and other modeling approaches was evaluated
      throughout the processing of dry and semidry FRMS. The greatest inactivation of
      VTEC was predicted in dry FRMS with long drying periods, while the smallest
      reduction was predicted in semidry FMRS with short drying periods. The model is
      implemented in a computing tool, E. coli SafeFerment (EcSF), freely available
      from http://www.ifr.ac.uk/safety/EcoliSafeFerment. EcSF integrates growth,
      probability of growth, and thermal and nonthermal inactivation models to predict
      the VTEC concentration throughout FRMS manufacturing and storage under constant
      or fluctuating environmental conditions. 

PMID- 24561588
TI  - Dimethylglycine provides salt and temperature stress protection to Bacillus
      subtilis.
AB  - Glycine betaine is a potent osmotic and thermal stress protectant of many
      microorganisms. Its synthesis from glycine results in the formation of the
      intermediates monomethylglycine (sarcosine) and dimethylglycine (DMG), and these
      compounds are also produced when it is catabolized. Bacillus subtilis does not
      produce sarcosine or DMG, and it cannot metabolize these compounds. Here we have
      studied the potential of sarcosine and DMG to protect B. subtilis against
      osmotic, heat, and cold stress. Sarcosine, a compatible solute that possesses
      considerable protein-stabilizing properties, did not serve as a stress protectant
      of B. subtilis. DMG, on the other hand, proved to be only moderately effective as
      an osmotic stress protectant, but it exhibited good heat stress-relieving and
      excellent cold stress-relieving properties. DMG is imported into B. subtilis
      cells primarily under osmotic and temperature stress conditions via OpuA, a
      member of the ABC family of transporters. Ligand-binding studies with the
      extracellular solute receptor (OpuAC) of the OpuA system showed that OpuAC
      possesses a moderate affinity for DMG, with a Kd value of approximate 172 MUM;
      its Kd for glycine betaine is about 26 MUM. Docking studies using the crystal
      structures of the OpuAC protein with the sulfur analog of DMG,
      dimethylsulfonioacetate, as a template suggest a model of how the DMG molecule
      can be stably accommodated within the aromatic cage of the OpuAC ligand-binding
      pocket. Collectively, our data show that the ability to acquire DMG from
      exogenous sources under stressful environmental conditions helps the B. subtilis
      cell to cope with growth-restricting osmotic and temperature challenges. 

PMID- 24561589
TI  - Effects of metal ions on stability and activity of hyperthermophilic pyrolysin
      and further stabilization of this enzyme by modification of a Ca2+-binding site.
AB  - Pyrolysin is an extracellular subtilase produced by the marine hyperthermophilic
      archaeon Pyrococcus furiosus. This enzyme functions at high temperatures in
      seawater, but little is known about the effects of metal ions on the properties
      of pyrolysin. Here, we report that the supplementation of Na(+), Ca(2+), or
      Mg(2+) salts at concentrations similar to those in seawater destabilizes
      recombinant pyrolysin but leads to an increase in enzyme activity. The
      destabilizing effect of metal ions on pyrolysin appears to be related to the
      disturbance of surface electrostatic interactions of the enzyme. In addition,
      mutational analysis of two predicted high-affinity Ca(2+)-binding sites (Ca1 and
      Ca2) revealed that the binding of Ca(2+) is important for the stabilization of
      this enzyme. Interestingly, Asn substitutions at residues Asp818 and Asp820 of
      the Ca2 site, which is located in the C-terminal extension of pyrolysin, resulted
      in improvements in both enzyme thermostability and activity without affecting
      Ca(2+)-binding affinity. These effects were most likely due to the elimination of
      unfavorable electrostatic repulsion at the Ca2 site. Together, these results
      suggest that metal ions play important roles in modulating the stability and
      activity of pyrolysin. 

PMID- 24561590
TI  - Gene and protein sequence optimization for high-level production of fully active
      and aglycosylated lysostaphin in Pichia pastoris.
AB  - Lysostaphin represents a promising therapeutic agent for the treatment of
      staphylococcal infections, in particular those of methicillin-resistant
      Staphylococcus aureus (MRSA). However, conventional expression systems for the
      enzyme suffer from various limitations, and there remains a need for an efficient
      and cost-effective production process to facilitate clinical translation and the
      development of nonmedical applications. While Pichia pastoris is widely used for
      high-level production of recombinant proteins, there are two major barriers to
      the production of lysostaphin in this industrially relevant host: lack of
      expression from the wild-type lysostaphin gene and aberrant glycosylation of the
      wild-type protein sequence. The first barrier can be overcome with a synthetic
      gene incorporating improved codon usage and balanced A+T/G+C content, and the
      second barrier can be overcome by disrupting an N-linked glycosylation sequon
      using a broadened choice of mutations that yield aglyscosylated and fully active
      lysostaphin. The optimized lysostaphin variants could be produced at
      approximately 500 mg/liter in a small-scale bioreactor, and 50% of that material
      could be recovered at high purity with a simple 2-step purification. It is
      anticipated that this novel high-level expression system will bring down one of
      the major barriers to future development of biomedical, veterinary, and research
      applications of lysostaphin and its engineered variants. 

PMID- 24561585
TI  - Multilocus sequence typing identifies epidemic clones of Flavobacterium
      psychrophilum in Nordic countries.
AB  - Flavobacterium psychrophilum is the causative agent of bacterial cold water
      disease (BCWD), which affects a variety of freshwater-reared salmonid species. A
      large-scale study was performed to investigate the genetic diversity of F.
      psychrophilum in the four Nordic countries: Denmark, Finland, Norway, and Sweden.
      Multilocus sequence typing of 560 geographically and temporally disparate F.
      psychrophilum isolates collected from various sources between 1983 and 2012
      revealed 81 different sequence types (STs) belonging to 12 clonal complexes (CCs)
      and 30 singleton STs. The largest CC, CC-ST10, which represented almost
      exclusively isolates from rainbow trout and included the most predominant
      genotype, ST2, comprised 65% of all isolates examined. In Norway, with a shorter
      history (<10 years) of BCWD in rainbow trout, ST2 was the only isolated CC-ST10
      genotype, suggesting a recent introduction of an epidemic clone. The study
      identified five additional CCs shared between countries and five country-specific
      CCs, some with apparent host specificity. Almost 80% of the singleton STs were
      isolated from non-rainbow trout species or the environment. The present study
      reveals a simultaneous presence of genetically distinct CCs in the Nordic
      countries and points out specific F. psychrophilum STs posing a threat to the
      salmonid production. The study provides a significant contribution toward mapping
      the genetic diversity of F. psychrophilum globally and support for the existence
      of an epidemic population structure where recombination is a significant driver
      in F. psychrophilum evolution. Evidence indicating dissemination of a putatively
      virulent clonal complex (CC-ST10) with commercial movement of fish or fish
      products is strengthened. 

PMID- 24561591
TI  - Synthesis of flavonoid O-pentosides by Escherichia coli through engineering of
      nucleotide sugar pathways and glycosyltransferase.
AB  - Plants produce two flavonoid O-pentoses, flavonoid O-xyloside and flavonoid O
      arabinoside. However, analyzing their biological properties is difficult because
      flavonoids are not naturally produced in sufficient quantities. In this study,
      Escherichia coli was used to synthesize the plant-specific flavonoid O-pentosides
      quercetin 3-O-xyloside and quercetin 3-O-arabinoside. Two strategies were used.
      First, E. coli was engineered to express components of the biosynthetic pathways
      for UDP-xylose and UDP-arabinose. For UDP-xylose biosynthesis, two genes, UXS
      (UDP-xylose synthase) from Arabidopsis thaliana and ugd (UDP-glucose
      dehydrogenase) from E. coli, were overexpressed. In addition, the gene encoding
      ArnA (UDP-l-Ara4N formyltransferase/UDP-GlcA C-4"-decarboxylase), which competes
      with UXS for UDP-glucuronic acid, was deleted. For UDP-arabinose biosynthesis,
      UXE (UDP-xylose epimerase) was overexpressed. Next, we engineered UDP-dependent
      glycosyltransferases (UGTs) to ensure specificity for UDP-xylose and UDP
      arabinose. The E. coli strains thus obtained synthesized approximately 160
      mg/liter of quercetin 3-O-xyloside and quercetin 3-O-arabinoside. 

PMID- 24561592
TI  - Survival of airborne MS2 bacteriophage generated from human saliva, artificial
      saliva, and cell culture medium.
AB  - Laboratory studies of virus aerosols have been criticized for generating airborne
      viruses from artificial nebulizer suspensions (e.g., cell culture media), which
      do not mimic the natural release of viruses (e.g., from human saliva). The
      objectives of this study were to determine the effect of human saliva on the
      infectivity and survival of airborne virus and to compare it with those of
      artificial saliva and cell culture medium. A stock of MS2 bacteriophage was
      diluted in one of three nebulizer suspensions, aerosolized, size selected (100 to
      450 nm) using a differential mobility analyzer, and collected onto gelatin
      filters. Uranine was used as a particle tracer. The resulting particle size
      distribution was measured using a scanning mobility particle sizer. The amounts
      of infectious virus, total virus, and fluorescence in the collected samples were
      determined by infectivity assays, quantitative reverse transcription-PCR (RT
      PCR), and spectrofluorometry, respectively. For all nebulizer suspensions, the
      virus content generally followed a particle volume distribution rather than a
      number distribution. The survival of airborne MS2 was independent of particle
      size but was strongly affected by the type of nebulizer suspension. Human saliva
      was found to be much less protective than cell culture medium (i.e., 3% tryptic
      soy broth) and artificial saliva. These results indicate the need for caution
      when extrapolating laboratory results, which often use artificial nebulizer
      suspensions. To better assess the risk of airborne transmission of viral diseases
      in real-life situations, the use of natural suspensions such as saliva or
      respiratory mucus is recommended. 

PMID- 24561594
TI  - Including stretches to a massage routine improves recovery from official matches
      in basketball players.
AB  - The aim of this study was to investigate the effect of incorporating stretches
      into a massage recovery treatment after a competitive basketball match on
      perceptual and physical markers of recovery. Nine men (age: 22 +/- 3 years;
      stature: 191.2 +/- 8.5 cm; body mass: 90.9 +/- 10.1 kg; and body fat: 12.4 +/-
      4.7%) and 8 women (age: 21 +/- 3 years; stature: 176.4 +/- 8.1 cm; body mass:
      73.9 +/- 9.7 kg; and body fat: 21.9 +/- 5.5%) who are national-level basketball
      players received a massage, a massage and stretching, or no treatment immediately
      after a competitive match. The perception of overall fatigue and leg soreness was
      assessed immediately after the treatment and 24 hours later, whereas
      countermovement jump (CMJ) and repeated sprint ability (RSA) were tested 24 hours
      after the treatment. Compared with massage, massage and stretching induced lower
      perception of leg soreness immediately only in women (p <= 0.001; (Equation is
      included in full-text article.)= 0.86), whereas a longer lasting effect was
      observed in men, with a difference between treatments reported after 24 hours (p
      <= 0.001; (Equation is included in full-text article.)= 0.94). Furthermore, both
      treatments resulted in a better CMJ performance compared with the control
      condition in men only (p = 0.0001; (Equation is included in full-text article.)=
      0.33), and massage and stretching involved a lower performance decrement during
      RSA compared with massage in women only (p = 0.015; (Equation is included in full
      text article.)= 0.29). The results suggest that women benefit slightly more from
      the combination treatment than men, and therefore this type of recovery
      intervention should be adopted by physiotherapists working with women teams in
      particular.

PMID- 24561595
TI  - Reliability of intestinal temperature using an ingestible telemetry pill system
      during exercise in a hot environment.
AB  - Ingestible telemetry pill systems are being increasingly used to assess the
      intestinal temperature during exercise in hot environments. The purpose of this
      investigation was to assess the interday reliability of intestinal temperature
      during an exercise-heat challenge. Intestinal temperature was recorded as 12
      physically active men (25 +/- 4 years, stature 181.7 +/- 7.0 cm, body mass 81.1
      +/- 10.6 kg) performed two 60-minute bouts of recumbent cycling (50% of peak
      aerobic power [watts]) in an environmental chamber set at 35 degrees  C 50%
      relative humidity 3-10 days apart. A range of statistics were used to calculate
      the reliability, including a paired t-test, 95% limits of agreement (LOA),
      coefficient of variation (CV), standard error of measurement (SEM), Pearson's
      correlation coefficient (r), intraclass correlation coefficient (ICC), and
      Cohen's d. Statistical significance was set at p <= 0.05. The method indicated a
      good overall reliability (LOA = +/- 0.61 degrees  C, CV = 0.58%, SEM = 0.12
      degrees  C, Cohen's d = 0.12, r = 0.84, ICC = 0.84). Analysis revealed a
      statistically significant (p = 0.02) mean systematic bias of -0.07 +/- 0.31
      degrees  C, and the investigation of the Bland-Altman plot suggested the presence
      of heteroscedasticity. Further analysis revealed the minimum "likely" change in
      intestinal temperature to be 0.34 degrees  C. Although the method demonstrates a
      good reliability, researchers should be aware of heteroscedasticity. Changes in
      intestinal temperature >0.34 degrees  C as a result of exercise or an
      intervention in a hot environment are likely changes and less influenced by error
      associated with the method.

PMID- 24561593
TI  - Abundance of broad bacterial taxa in the sargasso sea explained by environmental
      conditions but not water mass.
AB  - To explore the potential linkage between distribution of marine bacterioplankton
      groups, environmental conditions, and water mass, we investigated the factors
      determining the abundance of bacterial taxa across the hydrographically complex
      Subtropical Convergence Zone in the Sargasso Sea. Based on information from 16S
      rRNA gene clone libraries from various locations and two depths, abundances of
      the predominant taxa (eubacteria, Archaea, Alphaproteobacteria,
      Gammaproteobacteria, Bacteroidetes, and the Roseobacter, SAR11, and SAR86 clades)
      were quantified by real-time PCR. In addition, the abundances of Synechococcus,
      Prochlorococcus, and picoalgae were determined by flow cytometry. Linear multiple
      regression models determining the relative effects of eight environmental
      variables and of water mass explained 35 to 86% of the variation in abundance of
      the quantified taxa, even though only one to three variables were significantly
      related to any particular taxon's abundance. Most of the variation in abundance
      was explained by depth and chlorophyll a. The predominant phototrophs,
      Prochlorococcus and picoalgae, were negatively correlated with phosphate, whereas
      eubacteria, heterotrophic bacteria, and SAR86 were negatively correlated with
      nitrite. Water mass showed limited importance for explaining the abundance of the
      taxonomical groups (significant only for Roseobacter, explaining 14% of the
      variation). The results suggest the potential for predicting the abundance of
      broad bacterioplankton groups throughout the Sargasso Sea using only a few
      environmental parameters. 

PMID- 24561596
TI  - A conceptual framework for clutch-size evolution in songbirds.
AB  - Causes of evolved differences in clutch size among songbird species remain
      debated. I propose a new conceptual framework that integrates aspects of
      traditional life-history theory while including novel elements to explain
      evolution of clutch size among songbirds. I review evidence that selection by
      nest predation on length of time that offspring develop in the nest creates a
      gradient in offspring characteristics at nest leaving (fledging), including
      flight mobility, spatial dispersion, and self-feeding rate. I postulate that this
      gradient has consequences for offspring mortality rates and parental energy
      expenditure per offspring. These consequences then determine how reproductive
      effort is partitioned among offspring, while reproductive effort evolves from age
      specific mortality effects. Using data from a long-term site in Arizona, as well
      as from the literature, I provide support for hypothesized relationships.
      Nestling development period consistently explains fledgling mortality, energy
      expenditure per offspring, and clutch size while accounting for reproductive
      effort (i.e., total energy expenditure) to thereby support the framework. Tests
      in this article are not definitive, but they document previously unrecognized
      relationships and address diverse traits (developmental strategies, parental care
      strategies, energy requirements per offspring, evolution of reproductive effort,
      clutch size) that justify further investigations of hypotheses proposed here.

PMID- 24561597
TI  - Species collapse via hybridization in Darwin's tree finches.
AB  - Species hybridization can lead to fitness costs, species collapse, and novel
      evolutionary trajectories in changing environments. Hybridization is predicted to
      be more common when environmental conditions change rapidly. Here, we test
      patterns of hybridization in three sympatric tree finch species (small tree finch
      Camarhynchus parvulus, medium tree finch Camarhynchus pauper, and large tree
      finch: Camarhynchus psittacula) that are currently recognized on Floreana Island,
      Galapagos Archipelago. Genetic analysis of microsatellite data from contemporary
      samples showed two genetic populations and one hybrid cluster in both 2005 and
      2010; hybrid individuals were derived from genetic population 1 (small morph) and
      genetic population 2 (large morph). Females of the large and rare species were
      more likely to pair with males of the small common species. Finch populations
      differed in morphology in 1852-1906 compared with 2005/2010. An unsupervised
      clustering method showed (a) support for three morphological clusters in the
      historical tree finch sample (1852-1906), which is consistent with current
      species recognition; (b) support for two or three morphological clusters in 2005
      with some (19%) hybridization; and (c) support for just two morphological
      clusters in 2010 with frequent (41%) hybridization. We discuss these findings in
      relation to species demarcations of Camarhynchus tree finches on Floreana Island.

PMID- 24561598
TI  - Lottery coexistence on rocky shores: weak niche differentiation or equal
      competitors engaged in neutral dynamics?
AB  - Reconciling how niche and neutral processes may be important in species
      coexistence has revealed two important weaknesses in our collective understanding
      of species diversity: few empirical studies have determined whether species are
      truly coexisting, and fewer still have properly evaluated whether coexistence is
      achieved through niche differentiation or ecological equivalence. Here, we ask
      whether two common barnacles, Jehlius cirratus and Notochthamalus scabrosus,
      coexist locally and whether the slight but persistent differences in their
      distribution provide sufficient fitness trade-offs to overcome differences in
      competition. Both species recovered after experimental reduction; that is, they
      coexist, with no indication of hierarchical exclusion. No fitness inequalities
      affected species performance or interference effects on vital rates at any shore
      level, indicating no trade-offs in intra-interspecific effects across the
      ecological gradient. Additionally, no relationship was found between per capita
      population growth rates of either species with its own relative abundance; that
      is, neither species has a demographic advantage when rare. Instead, a lottery for
      space during settlement largely determines species' distributions, evidenced by
      the positive correlation across sites and tidal elevations between the relative
      abundances of adults and the recruits of the prior season. We conclude that
      Jehlius and Notochthamalus coexist neutrally, or nearly so, but discuss whether
      small, nonsignificant, and probably ephemeral fitness differences, which are
      inconsistent across the tidal gradient, could provide enough niche
      differentiation to promote coexistence.

PMID- 24561600
TI  - Adaptive and selective seed abortion reveals complex conditional decision making
      in plants.
AB  - Behavior is traditionally attributed to animals only. Recently, evidence for
      plant behavior is accumulating, mostly from plant physiological studies. Here, we
      provide ecological evidence for complex plant behavior in the form of seed
      abortion decisions conditional on internal and external cues. We analyzed seed
      abortion patterns of barberry plants exposed to seed parasitism and different
      environmental conditions. Without abortion, parasite infestation of seeds can
      lead to loss of all seeds in a fruit. We statistically tested a series of null
      models with Monte Carlo simulations to establish selectivity and adaptiveness of
      the observed seed abortion patterns. Seed abortion was more frequent in
      parasitized fruits and fruits from dry habitats. Surprisingly, seed abortion
      occurred with significantly greater probability if there was a second intact seed
      in the fruit. This strategy provides a fitness benefit if abortion can prevent a
      sibling seed from coinfestation and if nonabortion of an infested but surviving
      single seed saves resources invested in the fruit coat. Ecological evidence for
      complex decision making in plants thus includes a structural memory (the second
      seed), simple reasoning (integration of inner and outer conditions), conditional
      behavior (abortion), and anticipation of future risks (seed predation).

PMID- 24561599
TI  - Conflicting selection in the course of adaptive diversification: the interplay
      between mutualism and intraspecific competition.
AB  - Adaptive speciation can occur when a population undergoes assortative mating and
      disruptive selection caused by frequency-dependent intraspecific competition.
      However, other interactions, such as mutualisms based on trait matching, may
      generate conflicting selective pressures that constrain species diversification.
      We used individual-based simulations to explore how different types of mutualism
      affect adaptive diversification. A magic trait was assumed to simultaneously
      mediate mate choice, intraspecific competition, and mutualisms. In scenarios of
      intimate, specialized mutualisms, individuals interact with one or few individual
      mutualistic partners, and diversification is constrained only if the mutualism is
      obligate. In other scenarios, increasing numbers of different partners per
      individual limit diversification by generating stabilizing selection. Stabilizing
      selection emerges from the greater likelihood of trait mismatches for rare,
      extreme phenotypes than for common intermediate phenotypes. Constraints on
      diversification imposed by increased numbers of partners decrease if the trait
      matching degree has smaller positive effects on fitness. These results hold after
      the relaxation of various assumptions. When trait matching matters, mutualism
      generated stabilizing selection would thus often constrain diversification in
      obligate mutualisms, such as ant-myrmecophyte associations, and in low-intimacy
      mutualisms, including plant-seed disperser systems. Hence, different processes,
      such as trait convergence favoring the incorporation of nonrelated species, are
      needed to explain the higher richness of low-intimacy assemblages--shown here to
      be up to 1 order of magnitude richer than high-intimacy systems.

PMID- 24561601
TI  - Optimal life-history strategy differs between philopatric and dispersing
      individuals in a metapopulation.
AB  - Abundant empirical evidence for dispersal syndromes contrasts with the rarity of
      theoretical predictions about the evolution of life-history divergence between
      dispersing and philopatric individuals. We use an evolutionary model to predict
      optimal differences in age-specific reproductive effort between dispersing and
      philopatric individuals inhabiting the same metapopulation. In our model, only
      young individuals disperse, and their lifelong reproductive decisions are
      potentially affected by this initial event. Juvenile survival declines as density
      of adults and other juveniles increases. We assume a trade-off between
      reproduction and survival, so that different patterns of age-specific
      reproductive effort lead to different patterns of aging. We find that young
      immigrant mothers should allocate more resources to reproduction than young
      philopatric mothers, but these life-history differences vanish as immigrant and
      philopatric individuals get older. However, whether the higher early reproductive
      effort of immigrants results in higher fecundity depends on the postimmigration
      cost on fecundity. Dispersing individuals have consequently a shorter life span.
      Ultimately, these life-history differences are due to the fact that young
      dispersing individuals most often live in recently founded populations, where
      competition is relaxed and juvenile survival higher, favoring larger investment
      in offspring production at the expense of survival.

PMID- 24561602
TI  - Diversity, functional similarity, and top-down control drive synchronization and
      the reliability of ecosystem function.
AB  - The concept that diversity promotes reliability of ecosystem function depends on
      the pattern that community-level biomass shows lower temporal variability than
      species-level biomasses. However, this pattern is not universal, as it relies on
      compensatory or independent species dynamics. When in contrast within-trophic
      level synchronization occurs, variability of community biomass will approach
      population-level variability. Current knowledge fails to integrate how species
      richness, functional distance between species, and the relative importance of
      predation and competition combine to drive synchronization at different trophic
      levels. Here we clarify these mechanisms. Intense competition promotes
      compensatory dynamics in prey, but predators may at the same time increasingly
      synchronize, under increasing species richness and functional similarity. In
      contrast, predators and prey both show perfect synchronization under strong top
      down control, which is promoted by a combination of low functional distance and
      high net growth potential of predators. Under such conditions, community-level
      biomass variability peaks, with major negative consequences for reliability of
      ecosystem function.

PMID- 24561603
TI  - Ecological modeling of metabolic rates predicts diverging optima across food
      abundances.
AB  - Genetically based variation in metabolic rates of resting animals (RMR) suggests
      a potential role for evolutionary adaptations, but mechanistic models yielding
      evolutionary predictions are lacking. Here I utilize the increasingly recognized
      genetic correlation between RMR and activity metabolism and propose that
      optimality of the former is simply an outcome of selection on the latter. I
      develop a model for temporally stable environmental conditions that describes how
      the rate of acquisition of energy that can be converted into somatic growth and
      reproductive output can be expressed as a function of activity metabolism. One of
      the parameters in the model describes how food intake depends on activity and is
      hence a measure of food abundance. In contrast to the previously proposed
      hypothesis that individuals with a high RMR are at an advantage when
      environmental conditions are favorable, the model predicts that the optimal RMR
      is highest at an intermediate food abundance.

PMID- 24561604
TI  - Scaling of physical constraints at the root-soil interface to macroscopic
      patterns of nutrient retention in ecosystems.
AB  - Nutrient limitation in terrestrial ecosystems is often accompanied with
      maintaining a nearly closed vegetation-soil nutrient cycle. The ability to retain
      nutrients in an ecosystem requires the capacity of the plant-soil system to draw
      down nutrient levels in soils effectually such that export concentrations in soil
      solutions remain low. Here we address the physical constraints of plant nutrient
      uptake that may be limited by the diffusive movement of nutrients in soils, by
      the uptake at the root/mycorrhizal surface, and from interactions with soil water
      flow. We derive an analytical framework of soil nutrient transport and uptake and
      predict levels of plant available nutrient concentration and residence time. Our
      results, which we evaluate for nitrogen, show that the physical environment
      permits plants to lower soil solute concentration substantially. Our analysis
      confirms that plant uptake capacities in soils are considerable, such that water
      movement in soils is generally too small to significantly erode dissolved plant
      available nitrogen. Inorganic nitrogen concentrations in headwater streams are
      congruent with the prediction of our theoretical framework. Our framework offers
      a physical-based parameterization of nutrient uptake in ecosystem models and has
      the potential to serve as an important tool toward scaling biogeochemical cycles
      from individual roots to landscapes.

PMID- 24561605
TI  - Long-term effect of social interactions on behavioral plasticity and lifetime
      mating success.
AB  - Behavioral traits often change over an individual's lifetime. Experience,
      physiological senescence, and age-dependent differences in optimal behavior can,
      in theory, all cause longitudinal behavioral changes. Yet most studies of
      behavioral plasticity and selection on behavior focus on short-term population
      level responses to social factors such as conspecific density or sex ratio.
      Longer-term effects of social interactions on individual behavior have rarely
      been tested. Here we tested these effects by exposing male water striders
      (Hemiptera: Gerridae) to two different social conditions throughout their
      lifetime; we call these the nonsocial and social treatments. We then measured
      each male's lifetime mating success and individual behavioral plasticity by
      observing four different behaviors (exploring a novel environment, dispersal
      ability, sex-recognition sensitivity, and tendency to remount a resistant female
      after being dislodged) every 2 weeks. The social environment influenced
      individual variation in behavioral plasticity as well as population-level
      behavioral plasticity. Moreover, when we calculated linear selection gradients of
      individual behavioral traits and their plasticities on lifetime mating success,
      male remounting tendency and individual plasticity in exploration ability were
      likely to be the most important factors explaining variation in male lifetime
      mating success. In conclusion, the variation in social interactions throughout an
      individual's lifetime contributes to the individual variation in behavioral
      plasticity, which can significantly affect a male's lifetime fitness.

PMID- 24561606
TI  - Thermoregulatory behavior is widespread in the embryos of reptiles and birds.
AB  - Recent studies have demonstrated that thermoregulatory behavior occurs not only
      in posthatching turtles but also in turtles prior to hatching. Does
      thermoregulatory behavior also occur in the embryos of other reptile and bird
      species? Our experiments show that such behavior is widespread but not universal
      in reptile and bird embryos. We recorded repositioning within the egg, in
      response to thermal gradients, in the embryos of three species of snakes
      (Xenochrophis piscator, Elaphe bimaculata, and Zaocys dhumnades), two turtles
      (Chelydra serpentina and Ocadia sinensis), one crocodile (Alligator sinensis),
      and four birds (Coturnix coturnix, Gallus gallus domesticus, Columba livia
      domestica, and Anas platyrhynchos domestica). However, we detected no significant
      thermoregulation by the embryos of two lizard species (Takydromus septentrionalis
      and Phrynocephalus frontalis). Overall, embryonic thermoregulatory behavior is
      widespread in reptile as well as bird species but may be unimportant in the small
      eggs laid by most lizards.

PMID- 24561607
TI  - Spatial structure mitigates fitness costs in host-parasite coevolution.
AB  - The extent of population mixing is known to influence the coevolutionary outcomes
      of many host and parasite traits, including the evolution of generalism (the
      ability to resist or infect a broad range of genotypes). While the segregation of
      populations into interconnected demes has been shown to influence the evolution
      of generalism, the role of local interactions between individuals is unclear.
      Here, we combine an individual-based model of microbial communities with a well
      established framework of genetic specificity that matches empirical observations
      of bacterium-phage interactions. We find the evolution of generalism in well
      mixed populations to be highly sensitive to the severity of associated fitness
      costs, but the constraining effect of costs on the evolution of generalism is
      lessened in spatially structured populations. The contrasting outcomes between
      the two environments can be explained by different scales of competition (i.e.,
      global vs. local). These findings suggest that local interactions may have
      important effects on the evolution of generalism in host-parasite interactions,
      particularly in the presence of high fitness costs.

PMID- 24561608
TI  - Allee effects and the evolution of polymorphism in cyclic parthenogens.
AB  - Cyclic parthenogens alternate asexual reproduction with periodic episodes of
      sexual reproduction. Sexually produced free-living forms are often their only way
      to survive unfavorable periods. When sexual reproduction requires the mating of
      two self-incompatible individuals, mating limitation may generate an Allee
      effect, which makes small populations particularly vulnerable to extinction;
      parthenogenetic reproduction can attenuate this effect. However, asexual
      reproduction likely trades off with sexual reproduction. To explore the
      evolutionary implications of such a trade-off, we included recurrent mating
      events associated with seasonal interruptions in a simple population dynamics
      model. Following an adaptive dynamics approach, we showed that positive density
      dependence associated with Allee effects in cyclic parthenogens promotes
      evolutionary divergence in the level of investment in asexual reproduction.
      Although polymorphism may be transient, morphs mostly investing into sexual
      reproduction may eventually exclude those predominantly reproducing in an asexual
      manner. Asexual morphs can be seen as making cooperative investments into the
      common pool of mates, while sexual morphs defect, survive better, and may
      eventually fix in the population. Our findings provide a novel hypothesis for the
      frequent coexistence of sexual and asexual lineages, notably in plant parasitic
      fungi.

PMID- 24561609
TI  - Disease epidemiology in arthropods is altered by the presence of nonprotective
      symbionts.
AB  - Inherited microbial symbionts can modulate host susceptibility to natural enemy
      attack. A wider range of symbionts influence host population demography without
      altering individual susceptibility, and it has been suggested that these may
      modify host disease risk through altering the rate of exposure to natural
      enemies. We present the first test of this thesis, specifically testing whether
      male-killing symbionts alter the epidemiology of a sexually transmitted infection
      (STI) carried by its host. STIs are typically expected to show female-biased
      epidemics, and we first present a simple model which indicates that male-biased
      STI epidemics may occur where symbionts create female-biased population sex
      ratios. We then examined the dynamics of a STI in the ladybird beetle Adalia
      bipunctata, which is also host to a male-killing bacterium. We present evidence
      that male-biased epidemics of the STI are observed in natural populations when
      the male-killer is common. Laboratory experiments did not support a role for
      differential susceptibility of male and female hosts to the STI, nor a protective
      role for the symbiont, in creating this bias. We conclude that the range of
      symbionts likely to alter parasite epidemiology will be much wider than
      previously envisaged, because it will additionally include those that impact host
      demography alone.

PMID- 24561610
TI  - Limiting factors, competitive exclusion, and a more expansive view of species
      coexistence.

PMID- 24561611
TI  - Antimicrobial prophylaxis in minor and major surgery.
AB  - Surgical site infections (SSIs) are a frequent cause of morbidity following
      surgical procedures. Gram-positive cocci, particularly staphylococci, cause many
      of these infections, although Gram-negative organisms are also frequently
      involved. The risk of developing a SSI is associated with a number of factors,
      including aspects of the operative procedure itself, such as wound
      classification, and patient-related variables, such as preexisting medical
      conditions. Antimicrobial prophylaxis (AP) plays an important role in reducing
      SSIs, especially if patient-related risk factors for SSIs are present. The main
      components of antimicrobial prophylaxis are: timing, selection of drugs and
      patients, duration and costs. Compliance with these generally accepted preventive
      principles may lead to overall decreases in the incidence of these infections.
      Ideally the administration of the prophylactic agent should start within 30
      minutes from the surgical incision. The duration of the AP should not exceed 24
      hours for the majority of surgical procedures. The shortest effective period of
      prophylactic antimicrobial administration is not known and studies have
      demonstrated that post-surgical antibiotic administration is unnecessary.
      Furthermore, there were no proven benefits in multiple dose regimens when
      compared to single-dose regimens. The choice of an appropriate prophylactic
      antimicrobial agent should be based primarily on efficacy and safety. Broad
      spectrum antibiotics should be avoided due to the risk of promoting bacterial
      resistance. Cephalosporins are the most commonly used antibiotics in surgical
      prophylaxis; specifically, cefazolin or cefuroxime are mainly used in the
      prophylaxis regimens for cardio-thoracic surgery, vascular surgery, hip or knee
      arthroplasty surgery, neurosurgical procedures and gynecologic and obstetric
      procedures. A review of the prophylactic regimens regarding the main surgical
      procedures is presented. 

PMID- 24561612
TI  - Histamine H4 and H1 receptors contribute to postinflammatory visceral
      hypersensitivity.
AB  - OBJECTIVES: Substantial evidence implicates mast cells and their main constituent
      histamine in the pathogenesis of visceral hypersensitivity. We explored the
      specific contribution of histamine H4 (H4R) and H1 (H1R) receptors to visceral
      hypersensitivity in a postinflammatory rat model. DESIGN: Trinitrobenzenesulfonic
      acid (TNBS)-colitis was monitored individually by colonoscopy: first on day 3 to
      confirm the presence of colitis and then every 4 days, starting from day 10, to
      monitor convalescence and determine the exact timepoint of endoscopic healing in
      each rat. Experiments were performed 3 days after endoscopic resolution of
      colitis. Visceral sensitivity was assessed by quantifying visceromotor responses
      (VMRs) to colorectal distension. Colonic mast cell numbers, histamine release and
      H4R and H1R mRNA expression were quantified. JNJ7777120 (H4R antagonist) and/or
      levocetirizine (H1R antagonist) were administered 30 min prior to VMR assessment
      or histamine release assay. RESULTS: Postcolitis rats displayed a higher number
      of colonic mast cells, excessive histamine release and significantly enhanced
      VMRs. Heightened VMRs were dose-dependently reduced by JNJ7777120 and
      levocetirizine; combined administration of JNJ7777120 and levocetirizine
      potentiated the antinociceptive effect. In the colon, both H4R and H1R mRNA were
      present; in the dorsal root ganglia, only H1R mRNA was found. Only colonic H4R
      mRNA expression was increased in postcolitis rats. Excessive histamine release in
      postcolitis rats was attenuated by the highest dose of JNJ7777120. CONCLUSIONS:
      H4R and H1R antagonists dose-dependently reduce and even normalise
      postinflammatory visceral hypersensitivity via different underlying mechanisms
      but with a synergistic effect. Both receptor subtypes represent promising targets
      for the treatment of postinflammatory visceral hypersensitivity.

PMID- 24561614
TI  - Silicide induced ion beam patterning of Si(001).
AB  - Low energy ion beam pattern formation on Si with simultaneous co-deposition of
      Ag, Pd, Pb, Ir, Fe or C impurities was investigated by in situ scanning tunneling
      microscopy as well as ex situ atomic force microscopy, scanning electron
      microscopy, transmission electron microscopy and Rutherford backscattering
      spectrometry. The impurities were supplied by sputter deposition. Additional
      insight into the mechanism of pattern formation was obtained by more controlled
      supply through e-beam evaporation. For the situations investigated, the ability
      of the impurity to react with Si, i.e. to form a silicide, appears to be a
      necessary, but not a sufficient condition for pattern formation. Comparing the
      effects of impurities with similar mass and nuclear charge, the collision
      kinetics is shown to be not of primary importance for pattern formation. To
      understand the observed phenomena, it is necessary to assume a bi-directional
      coupling of composition and height fluctuations. This coupling gives rise to a
      sensitive dependence of the final morphology on the conditions of impurity
      supply. Because of this history dependence, the final morphology cannot be
      uniquely characterized by a steady state impurity concentration. 

PMID- 24561613
TI  - CCL2-dependent infiltrating macrophages promote angiogenesis in progressive liver
      fibrosis.
AB  - OBJECTIVES: In chronic liver injury, angiogenesis, the formation of new blood
      vessels from pre-existing ones, may contribute to progressive hepatic fibrosis
      and to development of hepatocellular carcinoma. Although hypoxia-induced
      expression of vascular endothelial growth factor (VEGF) occurs in advanced
      fibrosis, we hypothesised that inflammation may endorse hepatic angiogenesis
      already at early stages of fibrosis. DESIGN: Angiogenesis in livers of c57BL/6
      mice upon carbon tetrachloride- or bile duct ligation-induced chronic hepatic
      injury was non-invasively monitored using in vivo contrast-enhanced micro
      computed tomography (uCT) and ex vivo anatomical uCT after hepatic Microfil
      perfusion. Functional contributions of monocyte-derived macrophage subsets for
      angiogenesis were explored by pharmacological inhibition of CCL2 using the
      Spiegelmer mNOX-E36. RESULTS: Contrast-enhanced in vivo uCT imaging allowed non
      invasive monitoring of the close correlation of angiogenesis, reflected by
      functional hepatic blood vessel expansion, with experimental fibrosis
      progression. On a cellular level, inflammatory monocyte-derived macrophages
      massively accumulated in injured livers, colocalised with newly formed vessels in
      portal tracts and exhibited pro-angiogenic gene profiles including upregulated
      VEGF and MMP9. Functional in vivo and anatomical ex vivo uCT analyses
      demonstrated that inhibition of monocyte infiltration by targeting the chemokine
      CCL2 prevented fibrosis-associated angiogenesis, but not fibrosis progression.
      Monocyte-derived macrophages primarily fostered sprouting angiogenesis within the
      portal vein tract. Portal vein diameter as a measure of portal hypertension
      depended on fibrosis, but not on angiogenesis. CONCLUSIONS: Inflammation
      associated angiogenesis is promoted by CCL2-dependent monocytes during fibrosis
      progression. Innovative in vivo uCT methodology can accurately monitor
      angiogenesis and antiangiogenic therapy effects in experimental liver fibrosis.

PMID- 24561615
TI  - fourSig: a method for determining chromosomal interactions in 4C-Seq data.
AB  - The ability to correlate chromosome conformation and gene expression gives a
      great deal of information regarding the strategies used by a cell to properly
      regulate gene activity. 4C-Seq is a relatively new and increasingly popular
      technology where the set of genomic interactions generated by a single point in
      the genome can be determined. 4C-Seq experiments generate large, complicated data
      sets and it is imperative that signal is properly distinguished from noise.
      Currently, there are a limited number of methods for analyzing 4C-Seq data. Here,
      we present a new method, fourSig, which in addition to being precise and simple
      to use also includes a new feature that prioritizes detected interactions. Our
      results demonstrate the efficacy of fourSig with previously published and novel
      4C-Seq data sets and show that our significance prioritization correlates with
      the ability to reproducibly detect interactions among replicates. 

PMID- 24561616
TI  - Interactions between the non-seed region of siRNA and RNA-binding RLC/RISC
      proteins, Ago and TRBP, in mammalian cells.
AB  - Small interfering RNA (siRNA)-based RNA interference (RNAi) is widely used for
      target gene silencing in various organisms. We previously showed that 8-nt-long
      5' proximal nucleotides, which include seed sequence (positions 2-8 from the 5'
      end of guide strand), and the complementary sequence of the passenger strand are
      capable of being simultaneously replaced with cognate deoxyribonucleotides
      without any substantial loss of gene silencing. In the present study, examination
      was made of RNA requirements in the non-seed region of siRNA. The non-seed region
      of siRNA was found to be subdivided into four domains, in which two nucleotide
      pairs (positions 13 and 14) were replaceable with cognate deoxyribonucleotides
      without reducing RNAi activity. However, RNA sequences at positions 9-12 and 15
      18 were essential for effective gene silencing, and these two double-stranded RNA
      cores are required for binding of the trans-activation response RNA-binding
      protein (TRBP). The terminal RNA (positions 19-21) provided Argonaute protein
      binding sites. Argonaute binding was enhanced by the presence of RNAs at
      positions 15-18. Knockdown experiments showed that, unlike Argonaute and TRBP,
      Dicer was dispensable for RNAi. Based on these observations, we discuss possible
      RNA/protein and protein/protein interactions in RNA-induced silencing complex
      formation. 

PMID- 24561617
TI  - ADAR mediates differential expression of polycistronic microRNAs.
AB  - Adenosine deaminases acting on RNAs (ADARs) convert adenosine residues to
      inosines in primary microRNA (pri-miRNA) transcripts to alter the structural
      conformation of these precursors and the subsequent functions of the encoded
      microRNAs (miRNAs). Here we show that RNA editing by Drosophila ADAR modulates
      the expression of three co-transcribed miRNAs encoded by the evolutionarily
      conserved let-7-Complex (let-7-C) locus. For example, a single A-to-I change at
      the -6 residue of pri-miR-100, the first miRNA in this let-7-C polycistronic
      transcript, leads to enhanced miRNA processing by Drosha and consequently
      enhanced functional miR-100 both in vitro as well as in vivo. In contrast, other
      editing events, including one at the +43 residue of the pri-miR-125, destabilize
      the primary transcript and reduce the levels of all three encoded miRNAs.
      Consequently, loss of adar in vivo leads to reduced miR-100 but increased miR
      125. In wild-type animals, the destabilizing editing events in pri-let-7-C
      increase during the larval-to-adult transition and are critical for the normal
      downregulation of all three miRNAs seen late in metamorphosis. These findings
      unravel a new regulatory role for ADAR and raise the possibility that ADAR
      mediates the differential expression characteristic of many polycistronic miRNA
      clusters. 

PMID- 24561618
TI  - Mechanical control of the sense of touch by beta-spectrin.
AB  - The ability to sense and respond to mechanical stimuli emanates from sensory
      neurons and is shared by most, if not all, animals. Exactly how such neurons
      receive and distribute mechanical signals during touch sensation remains
      mysterious. Here, we show that sensation of mechanical forces depends on a
      continuous, pre-stressed spectrin cytoskeleton inside neurons. Mutations in the
      tetramerization domain of Caenorhabditis elegans beta-spectrin (UNC-70), an actin
      membrane crosslinker, cause defects in sensory neuron morphology under
      compressive stress in moving animals. Through atomic force spectroscopy
      experiments on isolated neurons, in vivo laser axotomy and fluorescence resonance
      energy transfer imaging to measure force across single cells and molecules, we
      show that spectrin is held under constitutive tension in living animals, which
      contributes to elevated pre-stress in touch receptor neurons. Genetic
      manipulations that decrease such spectrin-dependent tension also selectively
      impair touch sensation, suggesting that such pre-tension is essential for
      efficient responses to external mechanical stimuli. 

PMID- 24561619
TI  - Role of the SIK2-p35-PJA2 complex in pancreatic beta-cell functional
      compensation.
AB  - Energy sensing by the AMP-activated protein kinase (AMPK) is of fundamental
      importance in cell biology. In the pancreatic beta-cell, AMPK is a central
      regulator of insulin secretion. The capacity of the beta-cell to increase insulin
      output is a critical compensatory mechanism in prediabetes, yet its molecular
      underpinnings are unclear. Here we delineate a complex consisting of the AMPK
      related kinase SIK2, the CDK5 activator CDK5R1 (also known as p35) and the E3
      ligase PJA2 essential for beta-cell functional compensation. Following glucose
      stimulation, SIK2 phosphorylates p35 at Ser 91, to trigger its ubiquitylation by
      PJA2 and promote insulin secretion. Furthermore, SIK2 accumulates in beta-cells
      in models of metabolic syndrome to permit compensatory secretion; in contrast,
      beta-cell knockout of SIK2 leads to accumulation of p35 and impaired secretion.
      This work demonstrates that the SIK2-p35-PJA2 complex is essential for glucose
      homeostasis and provides a link between p35-CDK5 and the AMPK family in excitable
      cells.

PMID- 24561620
TI  - Nascent chromatin capture proteomics determines chromatin dynamics during DNA
      replication and identifies unknown fork components.
AB  - To maintain genome function and stability, DNA sequence and its organization into
      chromatin must be duplicated during cell division. Understanding how entire
      chromosomes are copied remains a major challenge. Here, we use nascent chromatin
      capture (NCC) to profile chromatin proteome dynamics during replication in human
      cells. NCC relies on biotin-dUTP labelling of replicating DNA, affinity
      purification and quantitative proteomics. Comparing nascent chromatin with mature
      post-replicative chromatin, we provide association dynamics for 3,995 proteins.
      The replication machinery and 485 chromatin factors such as CAF-1, DNMT1 and
      SUV39h1 are enriched in nascent chromatin, whereas 170 factors including histone
      H1, DNMT3, MBD1-3 and PRC1 show delayed association. This correlates with
      H4K5K12diAc removal and H3K9me1 accumulation, whereas H3K27me3 and H3K9me3 remain
      unchanged. Finally, we combine NCC enrichment with experimentally derived
      chromatin probabilities to predict a function in nascent chromatin for 93
      uncharacterized proteins, and identify FAM111A as a replication factor required
      for PCNA loading. Together, this provides an extensive resource to understand
      genome and epigenome maintenance. 

PMID- 24561621
TI  - Interplay of RhoA and mechanical forces in collective cell migration driven by
      leader cells.
AB  - The leading front of a collectively migrating epithelium often destabilizes into
      multicellular migration fingers where a cell initially similar to the others
      becomes a leader cell while its neighbours do not alter. The determinants of
      these leader cells include mechanical and biochemical cues, often under the
      control of small GTPases. However, an accurate dynamic cartography of both
      mechanical and biochemical activities remains to be established. Here, by mapping
      the mechanical traction forces exerted on the surface by MDCK migration fingers,
      we show that these structures are mechanical global entities with the leader
      cells exerting a large traction force. Moreover, the spatial distribution of RhoA
      differential activity at the basal plane strikingly mirrors this force
      cartography. We propose that RhoA controls the development of these fingers
      through mechanical cues: the leader cell drags the structure and the peripheral
      pluricellular acto-myosin cable prevents the initiation of new leader cells.

PMID- 24561624
TI  - In situ treatment of arsenic-contaminated groundwater by air sparging.
AB  - Arsenic contamination of groundwater is a major problem in some areas of the
      world, particularly in West Bengal (India) and Bangladesh where it is caused by
      reducing conditions in the aquifer. In situ treatment, if it can be proven as
      operationally feasible, has the potential to capture some advantages over other
      treatment methods by being fairly simple, not using chemicals, and not
      necessitating disposal of arsenic-rich wastes. In this study, the potential for
      in situ treatment by injection of compressed air directly into the aquifer (i.e.
      air sparging) is assessed. An experimental apparatus was constructed to simulate
      conditions of arsenic-rich groundwater under anaerobic conditions, and in situ
      treatment by air sparging was employed. Arsenic (up to 200 MUg/L) was removed to
      a maximum of 79% (at a local point in the apparatus) using a solution with
      dissolved iron and arsenic only. A static "jar" test revealed arsenic removal by
      co-precipitation with iron at a molar ratio of approximately 2 (iron/arsenic).
      This is encouraging since groundwater with relatively high amounts of dissolved
      iron (as compared to arsenic) therefore has a large theoretical treatment
      capacity for arsenic. Iron oxidation was significantly retarded at pH values
      below neutral. In terms of operation, analysis of experimental results shows that
      periodic air sparging may be feasible.

PMID- 24561622
TI  - The chromatin regulator Brg1 suppresses formation of intraductal papillary
      mucinous neoplasm and pancreatic ductal adenocarcinoma.
AB  - Pancreatic ductal adenocarcinoma (PDA) develops through distinct precursor
      lesions, including pancreatic intraepithelial neoplasia (PanIN) and intraductal
      papillary mucinous neoplasia (IPMN). However, genetic features resulting in IPMN
      associated PDA (IPMN-PDA) versus PanIN-associated PDA (PanIN-PDA) are largely
      unknown. Here we find that loss of Brg1, a core subunit of SWI/SNF chromatin
      remodelling complexes, cooperates with oncogenic Kras to form cystic neoplastic
      lesions that resemble human IPMN and progress to PDA. Although Brg1-null IPMN-PDA
      develops rapidly, it possesses a distinct transcriptional profile compared with
      PanIN-PDA driven by mutant Kras and hemizygous p53 deletion. IPMN-PDA also is
      less lethal, mirroring prognostic trends in PDA patients. In addition, Brg1
      deletion inhibits Kras-dependent PanIN development from adult acinar cells, but
      promotes Kras-driven preneoplastic transformation in adult duct cells. Therefore,
      this study implicates Brg1 as a determinant of context-dependent Kras-driven
      pancreatic tumorigenesis and suggests that chromatin remodelling may underlie the
      development of distinct PDA subsets. 

PMID- 24561625
TI  - Time multiplexing super resolving technique for imaging from a moving platform.
AB  - We propose a method for increasing the resolution of an object and overcoming the
      diffraction limit of an optical system installed on top of a moving imaging
      system, such as an airborne platform or satellite. The resolution improvement is
      obtained in a two-step process. First, three low resolution differently defocused
      images are being captured and the optical phase is retrieved using an improved
      iterative Gerchberg-Saxton based algorithm. The phase retrieval allows to
      numerically back propagate the field to the aperture plane. Second, the imaging
      system is shifted and the first step is repeated. The obtained optical fields at
      the aperture plane are combined and a synthetically increased lens aperture is
      generated along the direction of movement, yielding higher imaging resolution.
      The method resembles a well-known approach from the microwave regime called the
      Synthetic Aperture Radar (SAR) in which the antenna size is synthetically
      increased along the platform propagation direction. The proposed method is
      demonstrated through laboratory experiment. 

PMID- 24561623
TI  - MicroRNA-146a directs the symmetric division of Snail-dominant colorectal cancer
      stem cells.
AB  - Asymmetrical cell division (ACD) maintains the proper number of stem cells to
      ensure self-renewal. In cancer cells, the deregulation of ACD disrupts the
      homeostasis of the stem cell pool and promotes tumour growth. However, this
      mechanism is unclear. Here, we show a reduction of ACD in spheroid-derived
      colorectal cancer stem cells (CRCSCs) compared with differentiated cancer cells.
      The epithelial-mesenchymal transition (EMT) inducer Snail is responsible for the
      ACD-to-symmetrical cell division (SCD) switch in CRCSCs. Mechanistically, Snail
      induces the expression of microRNA-146a (miR-146a) through the beta-catenin-TCF4
      complex. miR-146a targets Numb to stabilize beta-catenin, which forms a feedback
      circuit to maintain Wnt activity and directs SCD. Interference with the Snail-miR
      146a-beta-catenin loop by inhibiting the MEK or Wnt activity reduces the
      symmetrical division of CRCSCs and attenuates tumorigenicity. In colorectal
      cancer patients, the Snail(High)Numb(Low) profile is correlated with cetuximab
      resistance and a poorer prognosis. This study elucidates a unique mechanism of
      EMT-induced CRCSC expansion.

PMID- 24561626
TI  - Biodrying of pulp and paper secondary sludge: kinetics of volatile solids
      biodegradation.
AB  - This study focuses on the kinetics of volatile solids (VS) biodegradation of the
      biodrying process using pulp and paper secondary sludge. The experiments were
      carried out with air-flow rates of 0.51, 1.61, 3.25 and 5.26L/minkgVS) and
      initial moisture content of 64-66% w.b. Using five kinetic models and a nonlinear
      regression method, kinetic parameters were estimated and the models were analyzed
      with two statistical indicators. Higher air-flow rates cause greater moisture
      content reduction, lower temperature in the matrix, and lower VS reduction. At an
      air-flow rate as high as 5.26L/minkgVS there is no biodrying but only convective
      drying. The kinetic models used successfully simulate the VS biodegradation under
      biodrying conditions, with a root mean square error (RMSE) between 0.007929 and
      0.02744. In conclusion, we show for the first time that VS biodegradation in the
      biodrying process can be successfully modeled with a kinetic model. 

PMID- 24561627
TI  - Advanced treatment of biologically pretreated coal gasification wastewater using
      a novel anoxic moving bed biofilm reactor (ANMBBR)-biological aerated filter
      (BAF) system.
AB  - A novel system integrating anoxic moving bed biofilm reactor (ANMBBR) and
      biological aerated filter (BAF) with short-cut biological nitrogen removal (SBNR)
      process was investigated as advanced treatment of real biologically pretreated
      coal gasification wastewater (CGW). The results showed the system had efficient
      capacity of degradation of pollutants especially nitrogen removal. The best
      performance was obtained at hydraulic residence times of 12h and nitrite
      recycling ratios of 200%. The removal efficiencies of COD, total organic carbon,
      NH4(+)-N, total phenols and total nitrogen (TN) were 74.6%, 70.0%, 85.0%, 92.7%
      and 72.3%, the corresponding effluent concentrations were 35.1, 18.0, 4.8, 2.2
      and 13.6mg/L, respectively. Compared with traditional A(2)/O process, the system
      had high performance of NH4(+)-N and TN removal, especially under the high toxic
      loading. Moreover, ANMBBR played a key role in eliminating toxicity and degrading
      refractory compounds, which was beneficial to improve biodegradability of raw
      wastewater for SBNR process. 

PMID- 24561628
TI  - Energy and exergy analysis of an ethanol reforming process for solid oxide fuel
      cell applications.
AB  - The fuel processor in which hydrogen is produced from fuels is an important unit
      in a fuel cell system. The aim of this study is to apply a thermodynamic concept
      to identify a suitable reforming process for an ethanol-fueled solid oxide fuel
      cell (SOFC). Three different reforming technologies, i.e., steam reforming,
      partial oxidation and autothermal reforming, are considered. The first and second
      laws of thermodynamics are employed to determine an energy demand and to describe
      how efficiently the energy is supplied to the reforming process. Effect of key
      operating parameters on the distribution of reforming products, such as H2, CO,
      CO2 and CH4, and the possibility of carbon formation in different ethanol
      reformings are examined as a function of steam-to-ethanol ratio, oxygen-to
      ethanol ratio and temperatures at atmospheric pressure. Energy and exergy
      analysis are performed to identify the best ethanol reforming process for SOFC
      applications. 

PMID- 24561629
TI  - Effect of particle size on the performance of autotrophic nitrogen removal in the
      granular sludge bed reactor and microbiological mechanisms.
AB  - The effect of particle size on the performance of autotrophic nitrogen removal in
      the granular sludge bed reactor (GSB-ANR) and microbiological mechanisms were
      investigated. The results indicated that performance of GSB-ANR process decreased
      gradually with the increase of the granular sludge size. Indeed small granules
      ranging between 0.5 and 0.9mm had a higher nitrogen removal capacity than large
      ones. The reasons of this effect were that (i) the aerobic ammonium oxidizing
      capacity of microorganisms was the bottle neck of nitrogen removal in GSB-ANR
      process, and the increase of aerobic ammonium oxidizing activity enhances nitrite
      production in nitrification and promotes subsequent nitrite consumption during
      anaerobic ammonia oxidation; (ii) the aerobic/anaerobic zone separation in
      granular sludge was the key factor affecting the aerobic ammonium oxidizing
      capacity of microorganisms. The small granules had a larger aerobic functional
      zone (75.1%) which was profitable for up-regulating the expression level of
      functional gene in aerobic ammonium oxidizing microorganisms. 

PMID- 24561630
TI  - Vibrating membrane filtration as improved technology for microalgae dewatering.
AB  - The effect of shear-enhanced filtration by vibratory process in microalgae
      dewatering is presented in this paper. The aim of this research was to
      investigate the technical performance and improvement of vibrating membrane
      filtration compared with conventional tangential cross-flow filtration in
      microalgae concentration. An industrial-scale available commercial set-up was
      used. Several membrane materials as polyethersulfone, polyacrylonitrile, etc.,
      and mean pore sizes (from 7000Da to 0.2MUm) were tested and compared in both
      filtration set-ups. Experiments were carried-out with Nannochloropsis gaditana
      and Phaeodactylum tricornutum microalgae. It has been demonstrated that, even if
      the choice of the membrane depends on its cut-off, its material and the type of
      microalgae filtrated, dynamic filtration is always the best technology over a
      conventional one. If with conventional filtration permeability values were in the
      vicinity of 10L/h/m(2)/bar in steady state phase, with dynamic filtration these
      values increased to 30L/h/m(2)/bar or more. 

PMID- 24561631
TI  - Oil palm trunk and sugarcane bagasse derived solid acid catalysts for rapid
      esterification of fatty acids and moisture-assisted transesterification of oils
      under pseudo-infinite methanol.
AB  - The use of pseudo-infinite methanol in increasing the rate of esterification and
      transesterification reactions was studied using oil palm trunk (OPT) and
      sugarcane bagasse (SCB) derived solid acid catalysts. The catalysts were prepared
      by incomplete carbonisation at 400 degrees C for 8h, followed by sulfonation at
      150 degrees C for 15h and characterised using TGA/DTA, XRD, FT-IR, SEM-EDS, EA
      and titrimetric determinations of acid sites. Under optimal reaction conditions,
      the process demonstrated rapid esterification of palmitic acid, with FAME yields
      of 93% and 94% in 45min for OPT and SCB catalysts, respectively. With the
      process, moisture levels up to 16.7% accelerated the conversion of low FFA oils
      by sulfonated carbon catalysts, through moisture-induced violent bumping.
      Moisture assisted transesterification of palm olein containing 1.78% FFA and
      8.33% added water gave FAME yield of 90% in 10h, which was two folds over neat
      oil. 

PMID- 24561633
TI  - Comparative evaluation of biogas production from poultry droppings, cow dung and
      lemon grass.
AB  - The study explored the production of biogas from Lemon grass, Cow dung and
      Poultry droppings. The three substrates were pre-fermented according to standard
      methods. Six (6) kg of each pre-fermented substrate was mixed with water in ratio
      1:1 v/v to form slurry and digested for 30days. A total of 0.125m(3), 0.191m(3)
      and 0.211m(3) of biogas were respectively produced from the Lemon grass, Cow dung
      and Poultry droppings with deviations of 0.00234m(3), 0.00289 m(3) and 0.00484
      m(3) respectively. The cooking test carried out revealed that the scrubbed gas
      had higher cooking rates for water (0.12L/min, 0.085L/min and 0.079L/min for
      Lemon grass, Cow dung and Poultry droppings respectively) while the cooking rates
      for unscrubbed gas were 0.079L/min, 0.064L/min and 0.06L/min respectively. The pH
      of the medium fluctuated optimally between 6.5 and 7.8. The research demonstrated
      that Lemon grass produced less volume but better quality biogas compared to Cow
      dung and Poultry droppings. 

PMID- 24561632
TI  - Assessment of two-phase olive mill solid waste and microalgae co-digestion to
      improve methane production and process kinetics.
AB  - Olive mill solid waste (OMSW) is a pollutant waste coming from olive oil
      elaboration by the two-phase centrifugation system. OMSW has a high organic
      matter content and unbalanced carbon to nitrogen (C/N) ratio, 31/1, which avoids
      obtaining high methane yields in the anaerobic digestion of this waste. In the
      present study a microalgae, Dunaliella salina, was employed as co-substrate for
      the OMSW anaerobic digestion in order to decrease the C/N ratio and increase its
      biodegradability. Different co-digestion mixtures (C/N ratios) were studied. The
      increase of D. salina from 25% to 50% in the co-digestion mixture clearly
      increased the biodegradability of the sole substrates. The highest
      biodegradability was found for the co-digestion mixture 50% OMSW-50% D. salina.
      Nevertheless, the maximum methane production, 330mLCH4/gVSadded, and the highest
      methane production rate were obtained for the co-digestion mixture 75% OMSW-25%
      D. salina, keeping a C/N ratio near to 26.7/1. 

PMID- 24561635
TI  - Normative adductor squeeze test values in elite junior rugby union players.
AB  - OBJECTIVE: To establish normative adductor squeeze test (AST) values in elite
      junior rugby union players and investigate if differences existed between field
      position units and categorizations. DESIGN: Cross-sectional study. SETTING:
      National underage screening camp. PARTICIPANTS: One hundred four healthy players
      attending an under-19 and under-18 national musculoskeletal and fitness screening
      camp. Players had no history of surgery, no self-reported history of groin or
      pelvic pain in either limb and no other lower limb injury in the past 3 months,
      and no pain reported during the testing procedure. MAIN OUTCOME MEASURES: The AST
      in 3 positions of hip flexion (0, 45, and 90 degrees), position unit, and
      categorizations. RESULTS: The highest AST values were observed at 45 degrees of
      hip flexion in all field position categories. No differences were observed
      between position units and categorizations. CONCLUSIONS: Normative AST values in
      an elite junior rugby union population were established in this investigation.
      Clinically, the sports medicine professional may use these results in making
      decisions on the management of both symptomatic and asymptomatic players.

PMID- 24561634
TI  - A systems biology-based investigation into the therapeutic effects of Gansui
      Banxia Tang on reversing the imbalanced network of hepatocellular carcinoma.
AB  - Several complex molecular events are involved in tumorigenesis of hepatocellular
      carcinoma (HCC). The interactions of these molecules may constitute the HCC
      imbalanced network. Gansui Banxia Tang (GSBXT), as a classic Chinese herbal
      formula, is a popular complementary and alternative medicine modality for
      treating HCC. In order to investigate the therapeutic effects and the
      pharmacological mechanisms of GSBXT on reversing HCC imbalanced network, we in
      the current study developed a comprehensive systems approach of integrating
      disease-specific and drug-specific networks, and successfully revealed the
      relationships of the ingredients in GSBXT with their putative targets, and with
      HCC significant molecules and HCC related pathway systems for the first time.
      Meanwhile, further experimental validation also demonstrated the preventive
      effects of GSBXT on tumor growth in mice and its regulatory effects on potential
      targets. 

PMID- 24561636
TI  - Effects of neck strength training on isometric neck strength in rugby union
      players.
AB  - OBJECTIVE: To investigate the effectiveness of a neck strengthening program on
      the isometric neck strength profile of male rugby union players. DESIGN:
      Controlled laboratory study. SETTING: Professional rugby union club.
      PARTICIPANTS: Fifteen professional and 10 semiprofessional rugby union players.
      INTERVENTIONS: The 15 professional players undertook a 5-week neck strengthening
      intervention, which was performed twice per week, whereas the 10 semiprofessional
      players acted as the control group. MAIN OUTCOME MEASURES: Isometric strength of
      the neck musculature was tested using a hand-held dynamometer, for flexion (F),
      extension (E), left-side flexion (LSF), and right-side flexion (RSF).
      Preintervention and postintervention evaluations were undertaken. RESULTS: No
      significant between-group differences in isometric neck strength were noted
      preintervention. A significant main effect for time was observed (P < 0.05),
      whereby the intervention group increased isometric neck strength in all planes
      after the 5-week intervention (F preintervention = 334.45 +/- 39.31 N vs F
      postintervention 396.05 +/- 75.55 N; E preintervention = 606.19 +/- 97.34 vs E
      postintervention = 733.88 +/- 127.16 N; LSF preintervention = 555.56 +/- 88.34 N
      vs LSF postintervention = 657.14 +/- 122.99 N; RSF preintervention = 570.00 +/-
      106.53 N vs RSF postintervention = 668.00 +/- 142.18 N). No significant
      improvement in neck strength was observed for control group participants.
      CONCLUSIONS: The results of the present study indicate that a 5-week neck
      strengthening program improves isometric neck strength in rugby union players,
      which may have implications for injury prevention, screening, and rehabilitation.
      CLINICAL RELEVANCE: The strengthening program described in the present study may
      facilitate rehabilitation specialists in the development of neck injury
      prevention, screening, and rehabilitation protocols.

PMID- 24561637
TI  - High altitude exposure alters gene expression levels of DNA repair enzymes, and
      modulates fatty acid metabolism by SIRT4 induction in human skeletal muscle.
AB  - We hypothesized that high altitude exposure and physical activity associated with
      the attack to Mt Everest could alter mRNA levels of DNA repair and metabolic
      enzymes and cause oxidative stress-related challenges in human skeletal muscle.
      Therefore, we have tested eight male mountaineers (25-40 years old) before and
      after five weeks of exposure to high altitude, which included attacks to peaks
      above 8000m. Data gained from biopsy samples from vastus lateralis revealed
      increased mRNA levels of both cytosolic and mitochondrial superoxide dismutase.
      On the other hand 8-oxoguanine DNA glycosylase (OGG1) mRNA levels tended to
      decrease while Ku70 mRNA levels and SIRT6 decreased with altitude exposure. The
      levels of SIRT1 and SIRT3 mRNA did not change significantly. However, SIRT4 mRNA
      level increased significantly, which could indicate decreases in fatty acid
      metabolism, since SIRT4 is one of the important regulators of this process.
      Within the limitations of this human study, data suggest that combined effects of
      high altitude exposure and physical activity climbing to Mt. Everest, could
      jeopardize the integrity of the particular chromosome. 

PMID- 24561638
TI  - Stem cell treatment for musculoskeletal disease.
AB  - Musculoskeletal disease is prevalent in society and with an ageing population,
      the incidence and impact on public health are set to rise. Severe long-term pain
      and mobility restriction impair the welfare and quality of life of patients with
      musculoskeletal disease. Current treatments are often restricted to the
      management of symptoms or temporary replacement with inert materials, rather than
      targeting prevention and cure. There is an urgent need for alternative biological
      approaches to musculoskeletal disease therapy. The rapid emergence of stem cell
      technologies, primarily using 'mesenchymal stem cells' (MSCs), has resulted in a
      number of pre-clinical and clinical studies in an effort to provide more
      effective treatment options. Challenges exist in bench-to-bedside translation,
      but they are not insurmountable. 

PMID- 24561640
TI  - Regulation of apoptosis in human gastric cancer cell line SGC-7901 by L-arginine.
AB  - AIM: L-arginine (L-Arg) is an aminoacid that has immunomodulating and antitumor
      effects. It is possible that antitumor effects of L-Arg are due to induction of
      apoptosis in tumor cells. The present study assessed antiproliferating and
      proapoptotic effects of L-Arg in human gastric cancer cell line SGC-7901.
      METHODS: Cell proliferation was quantified by MTT assay. Apoptosis was assessed
      using flow cytometry and FITC-Annexin-V/propidium iodide staining. Expression and
      activation of proteins pertinent to apoptosis (Bcl-2, surviving, p53, and XIAP)
      were studied using PCR, Western blot, and activity assays. RESULTS: L-Arg
      significantly inhibited growth of SCG-7901 gastric cancer cells and downregulated
      expression of antiapoptotic gene Bcl-2 and survivin. By contrast, expression of
      p53 was upregulated by L-Arg. CONCLUSION: Regulation of apoptosis by L-Arg via
      downregulation of antiapoptotic proteins Bcl-2 and surviving, and upregulation of
      proapoptotic protein p53 may represent the mechanism behind antitumor effects of
      L-Arg.

PMID- 24561641
TI  - Polyaniline/poly(epsilon-caprolactone) composite electrospun nanofiber-based gas
      sensors: optimization of sensing properties by dopants and doping concentration.
AB  - Electrospinning was utilized to synthesize a polyaniline (PANI)/poly(epsilon
      caprolactone) (PCL) composite in the form of nanofibers to examine its gas
      sensing performance. Electrical conductivity of the composite nanofibers was
      tailored by secondary doping with protonic acids including hydrochloride (HCl) or
      camphorsulfonic acid (HCSA). FT-IR and diffuse reflectance UV-vis spectroscopy
      were utilized to examine doping-dependent changes in the chemical structure and
      the protonation state of the nanofibers, respectively. The oxidation and
      protonation state of the composite nanofibers were shown to strongly depend on
      the doping agent and duration, demonstrating a simple way of controlling the
      electrical conductivity of the composite. PANI/PCL electrospun nanofibers having
      various electrical conductivities via varying dopants and doping concentrations,
      were configured to chemiresistors for sensing various analytes, including water
      vapor, NH3, and NO2. Secondary doping with Cl(-) and CSA differentially affected
      sensing behaviors by having distinctive optimal sensitivities. Biphasic
      sensitivity with respect to electrical conductivity was observed, demonstrating a
      facile method to enhance gas sensitivity by optimizing secondary doping. A
      balance between Debye length of the nanofibers and overall charge conduction may
      play an important role for modulating such an optimal sensitivity. 

PMID- 24561639
TI  - Negative confounding by essential fatty acids in methylmercury neurotoxicity
      associations.
AB  - BACKGROUND: Methylmercury, a worldwide contaminant of fish and seafood, can cause
      adverse effects on the developing nervous system. However, long-chain n-3
      polyunsaturated fatty acids in seafood provide beneficial effects on brain
      development. Negative confounding will likely result in underestimation of both
      mercury toxicity and nutrient benefits unless mutual adjustment is included in
      the analysis. METHODS: We examined these associations in 176 Faroese children, in
      whom prenatal methylmercury exposure was assessed from mercury concentrations in
      cord blood and maternal hair. The relative concentrations of fatty acids were
      determined in cord serum phospholipids. Neuropsychological performance in verbal,
      motor, attention, spatial, and memory functions was assessed at 7 years of age.
      Multiple regression and structural equation models (SEMs) were carried out to
      determine the confounder-adjusted associations with methylmercury exposure.
      RESULTS: A short delay recall (in percent change) in the California Verbal
      Learning Test (CVLT) was associated with a doubling of cord blood methylmercury (
      18.9, 95% confidence interval [CI]=-36.3, -1.51). The association became stronger
      after the inclusion of fatty acid concentrations in the analysis (-22.0, 95%
      confidence interval [CI]=-39.4, -4.62). In structural equation models, poorer
      memory function (corresponding to a lower score in the learning trials and short
      delay recall in CVLT) was associated with a doubling of prenatal exposure to
      methylmercury after the inclusion of fatty acid concentrations in the analysis (
      1.94, 95% CI=-3.39, -0.49). CONCLUSIONS: Associations between prenatal exposure
      to methylmercury and neurobehavioral deficits in memory function at school age
      were strengthened after fatty acid adjustment, thus suggesting that n-3 fatty
      acids need to be included in analysis of similar studies to avoid underestimation
      of the associations with methylmercury exposure.

PMID- 24561643
TI  - Is it safe to use supraglottic airway in children with difficult airways?

PMID- 24561642
TI  - The fastest Western in town: a contemporary twist on the classic Western blot
      analysis.
AB  - The Western blot techniques that were originally established in the late 1970s
      are still actively utilized today. However, this traditional method of Western
      blotting has several drawbacks that include low quality resolution, spurious
      bands, decreased sensitivity, and poor protein integrity. Recent advances have
      drastically improved numerous aspects of the standard Western blot protocol to
      produce higher qualitative and quantitative data. The Bis-Tris gel system, an
      alternative to the conventional Laemmli system, generates better protein
      separation and resolution, maintains protein integrity, and reduces
      electrophoresis to a 35 min run time. Moreover, the iBlot dry blotting system,
      dramatically improves the efficacy and speed of protein transfer to the membrane
      in 7 min, which is in contrast to the traditional protein transfer methods that
      are often more inefficient with lengthy transfer times. In combination with these
      highly innovative modifications, protein detection using infrared fluorescent
      imaging results in higher-quality, more accurate and consistent data compared to
      the standard Western blotting technique of chemiluminescence. This technology can
      simultaneously detect two different antigens on the same membrane by utilizing
      two-color near-infrared dyes that are visualized in different fluorescent
      channels. Furthermore, the linearity and broad dynamic range of fluorescent
      imaging allows for the precise quantification of both strong and weak protein
      bands. Thus, this protocol describes the key improvements to the classic Western
      blotting method, in which these advancements significantly increase the quality
      of data while greatly reducing the performance time of this experiment. 

PMID- 24561644
TI  - Volatile anaesthetics and positive pressure ventilation reduce left atrial
      performance: a transthoracic echocardiographic study in young healthy adults.
AB  - BACKGROUND: Animal and in vitro studies suggest that volatile anaesthetics affect
      left atrial (LA) performance. We hypothesized that human LA pump function and
      dimensions are altered by volatile anaesthetics in vivo. METHODS: We performed
      transthoracic echocardiographic (TTE) measurements in 59 healthy subjects (aged
      18-48 yr) undergoing minor surgery under general anaesthesia. The unpremedicated
      patients were randomly assigned to anaesthesia with sevoflurane, desflurane, or
      isoflurane. TTE examinations were performed at baseline and after induction of
      anaesthesia and upon placement of a laryngeal mask during spontaneous breathing.
      After changing to intermittent positive pressure ventilation (IPPV), an
      additional TTE was performed. The study focused on the velocity-time integral of
      late peak transmitral inflow velocity (AVTI) and maximum LA volume. RESULTS: We
      found no evidence for relevant differences in the effects of the three volatile
      anaesthetics. AVTI decreased significantly from 4.1 (1.2) cm at baseline to 3.2
      (1.1) cm during spontaneous breathing of 1 minimum alveolar concentration of
      volatile anaesthetics. AVTI decreased further to 2.8 (1.0) cm after changing to
      IPPV. The maximum LA volume was 45.4 (18.6) cm(3) at baseline and remained
      unchanged during spontaneous breathing but decreased to 34.5 (16.7) cm(3) during
      IPPV. Other parameters of LA pump function and dimensions decreased similarly.
      CONCLUSIONS: Volatile anaesthetics reduced active LA pump function in humans in
      vivo. Addition of IPPV decreased LA dimensions and further reduced LA pump
      function. Effects in vivo were less pronounced than previously found in in vitro
      and animal studies. Further studies are warranted to evaluate the clinical
      implications of these findings. CLINICAL TRIAL REGISTRATION: NCT0024451.

PMID- 24561645
TI  - Improving team information sharing with a structured call-out in anaesthetic
      emergencies: a randomized controlled trial.
AB  - BACKGROUND: Sharing information with the team is critical in developing a shared
      mental model in an emergency, and fundamental to effective teamwork. We developed
      a structured call-out tool, encapsulated in the acronym 'SNAPPI': Stop; Notify;
      Assessment; Plan; Priorities; Invite ideas. We explored whether a video-based
      intervention could improve structured call-outs during simulated crises and if
      this would improve information sharing and medical management. METHODS: In a
      simulation-based randomized, blinded study, we evaluated the effect of the video
      intervention teaching SNAPPI on scores for SNAPPI, information sharing, and
      medical management using baseline and follow-up crisis simulations. We assessed
      information sharing using a probe technique where nurses and technicians received
      unique, clinically relevant information probes before the simulation. Shared
      knowledge of probes was measured in a written, post-simulation test. We also
      scored sharing of diagnostic options with the team and medical management.
      RESULTS: Anaesthetists' scores for SNAPPI were significantly improved, as was the
      number of diagnostic options they shared. We found a non-significant trend to
      improve information-probe sharing and medical management in the intervention
      group, and across all simulations, a significant correlation between SNAPPI and
      information-probe sharing. Of note, only 27% of the clinically relevant
      information about the patient provided to the nurse and technician in the pre
      simulation information probes was subsequently learnt by the anaesthetist.
      CONCLUSIONS: We developed a structured communication tool, SNAPPI, to improve
      information sharing between anaesthetists and their team, taught it using a video
      based intervention, and provide initial evidence to support its value for
      improving communication in a crisis.

PMID- 24561646
TI  - A report of a new case of an interstitial deletion at 3p25.3 and expansion of the
      clinical phenotype.

PMID- 24561647
TI  - A patient with a de-novo deletion 3p25.3 and features overlapping with Rubinstein
      Taybi syndrome.

PMID- 24561648
TI  - The feasibility of the polycarbonate Durolon(TM) as a thermal neutron dosimeter.
AB  - The feasibility of Durolon as a thermal neutron dosimeter was studied. As
      experimentally determined the proposed methodology covers a wide range of doses,
      from 0.1 mSv<D<150 mSv, and can be used either for personal dosimetry or for area
      monitoring. Its insensitivity to visible light, beta and gamma radiations, makes
      the method attractive in order to evaluate neutron doses even in mixed radiation
      fields.

PMID- 24561649
TI  - Methodology for attainment of density and effective atomic number through dual
      energy technique using microtomographic images.
AB  - Dual energy technique for computerized microtomography shows itself as a
      promising method for identification of mineralogy on geological samples of
      heterogeneous composition. It can also assist with differentiating very similar
      objects regarding the attenuation coefficient, which are usually not separable
      during image processing and analysis of microtomographic data. Therefore, the
      development of a feasible and applicable methodology of dual energy in the
      analysis of microtomographic images was sought. 

PMID- 24561650
TI  - Application of solutions of Rhodamine B in dosimetry.
AB  - Aqueous solutions of the organic dye Rhodamine B were found to be useful in
      measuring radiation doses in the range 0.1-2 kGy. Either spectrophotometric or
      spectrofluorometric measurements can be used. The dosimeter readout is unchanged
      for at least 60 days after irradiation if the solution is kept in the dark at
      room temperature. Effects of pH and the dye concentration on the dosimeter
      response were investigated. Radiation chemical yield and fluorescence quantum
      yield were also calculated.

PMID- 24561651
TI  - Driving among patients with epilepsy in West China.
AB  - PURPOSE: This study was conducted to survey the driving status of PWE in West
      China and to explore the sociodemographic and clinical factors associated with
      driving. METHODS: Between October 2012 and October 2013, all adult patients who
      came to our epilepsy clinic in the West China Hospital were invited to
      participate. Logistic regression was used to detect the patient factors
      associated with driving. RESULTS: A total of 657 patients completed this study.
      We found that 128 (19.5%) of these patients had driven recently (during the past
      year); among them, 80 (62.5%) experienced at least one seizure in the previous
      year. A logistic regression suggested that age, being male, being married, having
      a higher personal income, experiencing no seizure while awake, and taking fewer
      antiepileptic drugs were independently associated with recent driving.
      CONCLUSION: This study showed that a considerable proportion of patients continue
      driving despite uncontrolled seizures. More detailed and operational driving
      restrictions may be needed for patients in China in order to strike a better
      balance between patients' quality of life and public safety.

PMID- 24561652
TI  - Quality indicators in an epilepsy monitoring unit.
AB  - Examining and improving the quality of care in epilepsy monitoring units (EMUs)
      is essential to delivering the best possible care and to mitigating undesirable
      outcomes. Epilepsy monitoring units are unique in that an admission to an EMU
      often involves the induction of symptoms (seizures) rather than minimizing and/or
      treating symptoms, which can lead to an increased risk to patient safety. Very
      little research has addressed the quality of care and safety in EMUs. The
      objective of this study was to examine quality indicators in a large population
      of patients admitted to an EMU in a large health region. Data were collected
      prospectively on 396 consecutive patients admitted to the EMU for scalp EEG
      recording from 2008 to 2011 using a standardized data abstraction form. Variables
      examined included the following: patient demographics, baseline clinical
      characteristics, EMU admission statistics, and EMU quality indicators. We found
      that an admission to the EMU was a safe and effective tool in the management of
      patients with epilepsy and seizure-like events. The number of adverse events
      during the study period was low at 4.9%. The admission question was answered in
      78.8% of cases, and it was partially answered in 6.6%. The need for
      systematically developed and validated quality indicators in EMUs is emphasized.
      The research in this area is sparse, and thus these data aid in supporting the
      utility of EMUs in the management and care of those with seizures and seizure
      like events. 

PMID- 24561653
TI  - High-intensity interval training every second week maintains VO2max in soccer
      players during off-season.
AB  - Reduced endurance training among semiprofessional soccer players during off
      season may have negative effect on game performance during the competition
      season. This negative effect can be prevented by adding high-intensity interval
      training (HIT) to normal activity. In this study, we want to compare 2 different
      frequencies of HIT (5 bouts of 4 minutes on 87-97% peak heart rate) session on
      maintenance of aerobic fitness among semiprofessional soccer players during a 6
      week off-season period. Seventeen male players at second and third highest soccer
      division in Norway participated. The subjects were randomized into 1 HIT session
      every second week (HIT 0.5) or 1 HIT session per week (HIT 1). All participants
      performed a 20-m shuttle run test and a maximal oxygen uptake (VO2max) test on
      treadmill before and after the training intervention. VO2max (HIT 0.5, 63.4 +/-
      5.9 ml.kg-1.min-1; HIT 1, 65.6 +/- 2.1 ml.kg-1.min-1) and 20-m shuttle run
      performance (HIT 0.5, 2335 +/- 390 m, HIT 1, 2531 +/- 106 m) were not different
      between the groups before the training intervention. VO2max was maintained after
      the training intervention in both HIT 0.5 and HIT 1 (64.0 +/- 5.9 ml.kg-1.min-1
      and 64.3 +/- 1.3 ml.kg-1.min-1, respectively). There was a reduction in distance
      covered during the 20-m shuttle run test in HIT 1 and when groups were pooled (
      7.9 +/- 5.7% and -6.4 +/- 7.9%, respectively, p <= 0.05). In conclusion, HIT 1
      did not maintain VO2max better than HIT 0.5 when added to normal off-season
      activity. However, performance in 20-m shuttle run, which is a more soccer
      specific fitness test than VO2max test, was slightly reduced when both groups was
      pooled.

PMID- 24561654
TI  - Epigenetic modifications in colorectal cancer: molecular insights and therapeutic
      challenges.
AB  - Colorectal cancer, a leading cause of mortality worldwide, is a multistep
      disorder that results from the alteration of genetic and epigenetic mechanisms
      under contextual influence. Epigenetic aberrations, including DNA methylation,
      histone modifications, chromatin remodeling and non-coding RNAs, affect every
      aspect of tumor development from initiation to metastasis. Cancer stem cell
      promotion is also included in the wide spectrum of epigenetic dysregulations.
      Elucidation of this complex crosstalk network may offer new insights in the
      molecular interactions involved in the pathogenesis of colorectal carcinogenesis.
      In the era of translational medicine new horizons are opened for the pursuit of
      personalized therapeutic approaches and the development of novel and accurate
      diagnostic, prognostic and therapy-assessment markers. This review discusses the
      implications of epigenetic mechanisms in tumor biology and their applications
      "from bench to bedside". 

PMID- 24561655
TI  - Validity of a novel wristband tonometer for measuring central hemodynamics and
      augmentation index.
AB  - BACKGROUND: Central hemodynamic and augmentation indices are independent
      predictors of cardiovascular events and all-cause mortality that can be estimated
      noninvasively by pulse wave analysis. The purpose of this study was to assess the
      reliability and validity of a newly engineered wristband tonometer for acquiring
      radial artery pressure waveforms. METHODS: Radial artery pulse pressure waveforms
      were evaluated with an established pencil-type and a novel wristband tonometer in
      31 participants (aged 30.2+/-9.5 years) resting in a supine position. Pulse wave
      analysis was executed using the same validated generalized transfer function
      (SphygmoCor) for both tonometers. RESULTS: A significant difference in time to
      data acquisition between tonometers was observed (-70.2+/-147.7 s; P < 0.05;
      wristband faster). The wristband tonometer had significantly lower within-subject
      coefficients of variation (CV) compared with the pencil-type tonometer in aortic
      pulse wave height (-2.67% +/- 5.51%; P < 0.05) and time to reflection (-2.26% +/-
      6.16%; P < 0.01). No other differences in CV were observed. Slight but
      statistically significant mean differences between tonometers were observed in
      aortic systolic blood pressure (ASBP; 0.43+/-1.08 mm Hg; P < 0.05; wristband
      lower), aortic pulse pressure (APP; 0.43+/-0.96 mm Hg; P < 0.05; wristband
      lower), and round-trip travel time of the reflected pressure wave (Deltatp;
      3.58+/-12.86 ms; P < 0.05; wristband higher). However, ASBP, APP, and Deltatp
      measurements were highly correlated (r = 0.9970, r = 0.9953, and r = 0.8838,
      respectively, P <0.0001) between tonometers; within-subject and between tonometer
      significant mean differences were within clinical ranges. CONCLUSIONS: This
      novel, hands-free platform may be interchangeable with the commonly used pencil
      type tonometer, heralding new directions in noninvasive in vivo vascular research
      and clinical application.

PMID- 24561656
TI  - Home blood pressure monitoring: a few minutes of rest before measurement may not
      be appropriate.
AB  - BACKGROUND: Home blood pressure measurement (HBPM) is recommended for the
      diagnosis and follow-up of hypertensive patients. While measurement protocols
      emphasize a rest period before taking the measurement, this directive has not
      been supported by any specific study to date. This analysis aimed to determine
      whether the respect or nonrespect of rest before HBPM could introduce a
      difference between daytime ambulatory blood pressure measurement (ABPM) and HBPM;
      whether this rest is observed "in real life" among educated hypertensive
      patients. METHODS: In this open, prospective study we compared HBPM, with and
      without rest, and ABPM among 52 office/clinically controlled hypertensive
      patients. HBPM was performed during 3 days (French HAS instructions); 24-hour
      ABPM was performed within 3 days of HBPM. All patients who regularly performed
      HBPM before the study were asked how they practiced HBPM in real life. RESULTS:
      There was a differential impact of rest on differences observed in daytime ABPM
      and HBPM. Systolic HBPM decreased with rest, while diastolic HBPM did not
      significantly increase. HBPM systolic BP (SBP) without rest was not significantly
      different from daytime ABPM SBP (P = 0.27). HBPM SBP without rest was lower than
      daytime and 24-hour systolic ABPM. Diastolic HBPM after rest was not
      significantly different from daytime diastolic ABPM (P = 0.09). None of the 38
      patients who regularly performed HBPM were compliant with a period of rest before
      beginning the measurements. CONCLUSIONS: Rest before HBPM induces a bias that
      underestimates SBP vs. daytime ABPM and perhaps complicates patient adherence to
      HBPM protocols.

PMID- 24561657
TI  - Flexibility of cold- and heat-adapted subtilisin-like serine proteinases
      evaluated with fluorescence quenching and molecular dynamics.
AB  - The subtilisin-like serine proteinases, VPR, from a psychrotrophic Vibrio species
      and aqualysin I (AQUI) from the thermophile Thermus aquaticus, are structural
      homologues, but differ significantly with respect to stability and catalytic
      properties. It has been postulated that the higher catalytic activity of cold
      adapted enzymes when compared to homologues from thermophiles, reflects their
      higher molecular flexibility. To assess a potential difference in molecular
      flexibility between the two homologous proteinases, we have measured their Trp
      fluorescence quenching by acrylamide at different temperatures. We also
      investigated protein dynamics of VPR and AQUI at an atomic level by molecular
      dynamics simulations. VPR contains four Trp residues, three of which are at
      corresponding sites in the structure of AQUI. To aid in the comparison, a Tyr at
      the fourth corresponding site in AQUI was mutated to Trp (Y191W). A lower
      quenching effect of acrylamide on the intrinsic fluorescence of the thermophilic
      AQUI_Y191W was observed at all temperatures measured (10-55 degrees C),
      suggesting that it possesses a more rigid structure than VPR. The MD analysis
      (Calpha rmsf profiles) showed that even though VPR and AQUI have similar
      flexibility profiles, the cold adapted VPR displays higher flexibility in most
      regions of the protein structure. Some of these regions contain or are in
      proximity to some of the Trp residues (Trp6, Trp114 and Trp208) in the proteins.
      Thus, we observe an overall agreement between the fluorescence quenching data and
      the flexibility profiles obtained from the MD simulations to different
      flexibilities of specific regions in the proteins. 

PMID- 24561658
TI  - Healthcare utilization and costs in children with stable and uncontrolled
      epilepsy.
AB  - OBJECTIVE: Epilepsy adversely affects childhood development, possibly leading to
      increased economic burden in pediatric populations. We compared annual healthcare
      utilization and costs between children (<12 years old) with stable and
      uncontrolled epilepsy treated with antiepileptic drugs (AEDs). METHODS: Children
      (<12 years old) with epilepsy (ICD-9-CM 345.xx or 780.39) in 2008 were identified
      in the MarketScan claims database from 2007 to 2009. Patients with "stable"
      epilepsy used the same AED for >=12 months, and patients with "uncontrolled"
      epilepsy were prescribed additional AED(s) during that period. For patients with
      uncontrolled epilepsy, the study index date was the start of additional AED(s);
      for patients with stable epilepsy, the study index date was a random AED fill
      date. Epilepsy-related utilization included medical services with 345.xx or
      780.39 in any diagnosis field and AED fills. Epilepsy-related costs included
      AEDs, medical claims with epilepsy in any diagnosis field, and certain tests. We
      adjusted for baseline cohort differences (demographics, region, usual-care
      physician specialty, and comorbidities) using logistic regression and analysis of
      covariance. RESULTS: Two thousand one hundred seventy patients were identified
      (mean: 7.5 years; 45.3% were female; Charlson comorbidity index: 0.3; 422 (19.4%)
      patients with uncontrolled epilepsy). Patients with uncontrolled epilepsy faced
      more hospitalizations (30.1% vs. 12.0%) and greater overall ($30,343 vs. $18,206)
      and epilepsy-related costs ($16,894 vs. $7979) (all p<.001). Adjusting for
      baseline measures, patients with uncontrolled epilepsy had greater odds of
      hospitalization (OR: 2.5; 95% CI: 1.9-3.3) and costs (overall: $3908, p=.087;
      epilepsy-related: $5744, p<.001). CONCLUSIONS: Children with uncontrolled
      epilepsy use significantly more healthcare resources and have a greater economic
      burden than children with stable epilepsy. However, epilepsy accounted for only
      half of overall costs, indicating that comorbid conditions may add substantially
      to the disease burden.

PMID- 24561659
TI  - Advantages of respiratory monitoring during video-EEG evaluation to differentiate
      epileptic seizures from other events.
AB  - Differentiating between epileptic seizures (ES) and seizure-like nonepileptic
      events (SLNE) is often difficult using descriptions of seizure semiology.
      Cardiopulmonary dysfunction is frequent in ES but has not been objectively
      examined in relation to SLNE. Our purpose was to compare cardiopulmonary
      dysfunction between ES and SLNE. We prospectively recorded cardiopulmonary
      function using pulse oximetry, EKG, and respiratory inductance plethysmography
      (RIP) in 52 ES and 22 SLNE. Comparison of cardiopulmonary complications between
      ES and SLNE was done using two-sample T-tests and logistic regression. Ictal
      bradypnea and preictal bradycardia were more frequent in ES than SLNE (p<0.05).
      Desaturation was found in 57% of ES and in 0% of SLNE (p<0.0001). Oxygen
      saturation nadir was significantly lower in ES vs. SLNE (p<0.0001). Ictal apnea
      was present in 31% ES and 9% SLNE (p=0.06). Preictal, ictal, and postictal
      tachycardia did not significantly differ between ES and SLNE (p>1.0).
      Cardiorespiratory dysfunction, specifically bradypnea, apnea, preictal
      bradycardia, and oxygen desaturation, is more frequently seen in ES than in SLNE.
      Tachycardia was not discriminant between ES and SLNE. 

PMID- 24561660
TI  - Quasi-light storage for optical data packets.
AB  - Today's telecommunication is based on optical packets which transmit the
      information in optical fiber networks around the world. Currently, the processing
      of the signals is done in the electrical domain. Direct storage in the optical
      domain would avoid the transfer of the packets to the electrical and back to the
      optical domain in every network node and, therefore, increase the speed and
      possibly reduce the energy consumption of telecommunications. However, light
      consists of photons which propagate with the speed of light in vacuum. Thus, the
      storage of light is a big challenge. There exist some methods to slow down the
      speed of the light, or to store it in excitations of a medium. However, these
      methods cannot be used for the storage of optical data packets used in
      telecommunications networks. Here we show how the time-frequency-coherence, which
      holds for every signal and therefore for optical packets as well, can be
      exploited to build an optical memory. We will review the background and show in
      detail and through examples, how a frequency comb can be used for the copying of
      an optical packet which enters the memory. One of these time domain copies is
      then extracted from the memory by a time domain switch. We will show this method
      for intensity as well as for phase modulated signals. 

PMID- 24561661
TI  - Tethered ligands reveal glutamate receptor desensitization depends on subunit
      occupancy.
AB  - Cell signaling is often mediated by the binding of multiple ligands to
      multisubunit receptors. The probabilistic nature and sometimes slow rate of
      binding encountered with diffusible ligands can impede attempts to determine how
      the ligand occupancy controls signaling in such protein complexes. We describe a
      solution to this problem that uses a photoswitched tethered ligand as a 'ligand
      clamp' to induce rapid and stable binding and unbinding at defined subsets of
      subunits. We applied the approach to study gating in ionotropic glutamate
      receptors (iGluRs), ligand-gated ion channels that mediate excitatory
      neurotransmission and plasticity at glutamatergic synapses in the brain. We
      probed gating in two kainate-type iGluRs, GluK2 homotetramers and GluK2-GluK5
      heterotetramers. Ultrafast (submillisecond) photoswitching of an azobenzene-based
      ligand on specific subunits provided a real-time measure of gating and revealed
      that partially occupied receptors can activate without desensitizing. The
      findings have implications for signaling by locally released and spillover
      glutamate. 

PMID- 24561663
TI  - N-Propargylated isatin-Mannich mono- and bis-adducts: synthesis and preliminary
      analysis of in vitro activity against Tritrichomonas foetus.
AB  - Cu(I)Cl promoted synthesis of N-propargylated-isatin Mannich mono- and bis
      adducts with an extension towards the synthesis of N-propargylated-isatin-7
      chloroquinoline conjugates was described. The synthesized scaffolds were
      evaluated for their in vitro activity against the veterinary protozoal pathogen
      Tritrichomonas foetus and cytotoxicity against human prostate (PC-3) cancer cell
      line. The preliminary evaluation data revealed the enhancement in the activity
      profiles with the introduction of 7-chloroquinoline ring with the most active
      conjugates 7a, 7c and 7d exhibiting an IC50 of 22.2, 11.3 and 24.5 MUM
      respectively against T. foetus and minimal toxicity against human prostate (PC-3)
      cell lines.

PMID- 24561662
TI  - Homogeneous low-molecular-weight heparins with reversible anticoagulant activity.
AB  - Low-molecular-weight heparins (LMWHs) are carbohydrate-based anticoagulants
      clinically used to treat thrombotic disorders, but impurities, structural
      heterogeneity or functional irreversibility can limit treatment options. We
      report a series of synthetic LMWHs prepared by cost-effective chemoenzymatic
      methods. The high activity of one defined synthetic LMWH against human factor Xa
      (FXa) was reversible in vitro and in vivo using protamine, demonstrating that
      synthetically accessible constructs can have a critical role in the next
      generation of LMWHs. 

PMID- 24561664
TI  - Dynamics of short- and long-term association between a bacterial plant pathogen
      and its arthropod vector.
AB  - The dynamics of association between pathogens and vectors can strongly influence
      epidemiology. It has been proposed that wilt disease epidemics in cucurbit
      populations are sustained by persistent colonization of beetle vectors (Acalymma
      vittatum) by the bacterial phytopathogen Erwinia tracheiphila. We developed a
      qPCR method to quantify E. tracheiphila in whole beetles and frass and used it to
      assess pathogen acquisition and retention following variable exposure to infected
      plants. We found that (i) E. tracheiphila is present in frass in as little as
      three hours after feeding on infected plants and can be transmitted with no
      incubation period by vectors given brief exposure to infected plants, but also by
      persistently colonized vectors several weeks following exposure; (ii) duration of
      exposure influences rates of long-term colonization; (iii) frass infectivity
      (assessed via inoculation experiments) reflects bacterial levels in frass samples
      across time; and (iv) vectors rarely clear E. tracheiphila infections, but suffer
      no apparent loss of fitness. These results describe a pattern conducive to the
      effective maintenance of E. tracheiphila within cucurbit populations. 

PMID- 24561666
TI  - Sorting of Streptomyces cell pellets using a complex object parametric analyzer
      and sorter.
AB  - Streptomycetes are filamentous soil bacteria that are used in industry for the
      production of enzymes and antibiotics. When grown in bioreactors, these organisms
      form networks of interconnected hyphae, known as pellets, which are heterogeneous
      in size. Here we describe a method to analyze and sort mycelial pellets using a
      Complex Object Parametric Analyzer and Sorter (COPAS). Detailed instructions are
      given for the use of the instrument and the basic statistical analysis of the
      data. We furthermore describe how pellets can be sorted according to user-defined
      settings, which enables downstream processing such as the analysis of the RNA or
      protein content. Using this methodology the mechanism underlying heterogeneous
      growth can be tackled. This will be instrumental for improving streptomycetes as
      a cell factory, considering the fact that productivity correlates with pellet
      size. 

PMID- 24561665
TI  - Digital inline holographic microscopy (DIHM) of weakly-scattering subjects.
AB  - Weakly-scattering objects, such as small colloidal particles and most biological
      cells, are frequently encountered in microscopy. Indeed, a range of techniques
      have been developed to better visualize these phase objects; phase contrast and
      DIC are among the most popular methods for enhancing contrast. However, recording
      position and shape in the out-of-imaging-plane direction remains challenging.
      This report introduces a simple experimental method to accurately determine the
      location and geometry of objects in three dimensions, using digital inline
      holographic microscopy (DIHM). Broadly speaking, the accessible sample volume is
      defined by the camera sensor size in the lateral direction, and the illumination
      coherence in the axial direction. Typical sample volumes range from 200 um x 200
      um x 200 um using LED illumination, to 5 mm x 5 mm x 5 mm or larger using laser
      illumination. This illumination light is configured so that plane waves are
      incident on the sample. Objects in the sample volume then scatter light, which
      interferes with the unscattered light to form interference patterns perpendicular
      to the illumination direction. This image (the hologram) contains the depth
      information required for three-dimensional reconstruction, and can be captured on
      a standard imaging device such as a CMOS or CCD camera. The Rayleigh-Sommerfeld
      back propagation method is employed to numerically refocus microscope images, and
      a simple imaging heuristic based on the Gouy phase anomaly is used to identify
      scattering objects within the reconstructed volume. This simple but robust method
      results in an unambiguous, model-free measurement of the location and shape of
      objects in microscopic samples. 

PMID- 24561667
TI  - Design and synthesis of thiazole derivatives as potent FabH inhibitors with
      antibacterial activity.
AB  - Components of fatty acid biosynthetic pathway have been identified as attractive
      targets for the development of new antibacterial agents. Compounds of series A
      (4a-4 g) and series B (5a-5 g) were synthesized by the formation of an amine bond
      between aromatic acid and 4-phenylthiazol-2-amine or 4-(4-bromophenyl)thiazol-2
      amine. These thiazole derivatives have evaluated as potent FabH inhibitors.
      Nineteen compounds (4b-4h, 4 k, 4 l, 5a-5h, 5k, 5l) are reported for the first
      time. Most of the synthesized compounds exhibited antibacterial activity in the
      MTT assay. The MIC value of these compounds ranged from 1.56 MUg/mL to 100
      MUg/mL. Moreover, the tested compounds also showed FabH inhibition ability with
      IC50 value ranging from 5.8 MUM to 48.1 MUM. The IC50 values are near the MIC
      values. Compound 5f has exhibited the best antibacterial and Escherichia coli
      FabH inhibitory activity. Docking simulation and the QSAR study was conducted for
      learning about binding mode and the relationship between structure and activity.

PMID- 24561668
TI  - Imidazopyridine-fused [1,3]-diazepinones: synthesis and antiproliferative
      activity.
AB  - A series of 15 pyrido-imidazo-1,3-diazepin-5-ones and pyrido-1,3-diazepine-2,5
      diones were synthesized and their anticancer activities were evaluated. Among
      tested compounds on a cell lines panel, compound 6a presents the best growth
      inhibition activity on 21 cell lines with a cytotoxic effect on MDA-MB-435
      melanoma cells. This compound led to deep cell morphological changes and revealed
      to be an inhibitor of the Hepatocyte progenitor kinase-like kinase (HGK), which
      is known to be implicated in the migration, adhesion and invasion of various
      tumor cells. 

PMID- 24561669
TI  - Synthesis and structure-activity relationship study of substituted caffeate
      esters as antinociceptive agents modulating the TREK-1 channel.
AB  - The TWIK-related K(+) channel, TREK-1, has recently emerged as an attractive
      therapeutic target for the development of a novel class of analgesic drugs. It
      has been reported that TREK-1 -/- mice were more sensitive than wild-type mice to
      painful stimuli, suggesting that activation of TREK-1 could result in pain
      inhibition. Here we report the synthesis of a series of substituted caffeate
      esters (12a-u) based on the hit compound CDC 2 (cinnamyl 3,4-dihydroxyl-alpha
      cyanocinnamate). These analogs were evaluated for their ability to modulate TREK
      1 channel by electrophysiology and for their in vivo antinociceptive activity
      (acetic acid induced-writhing assay) leading to the identification a series of
      novel molecules able to activate TREK-1 and displaying potent analgesic activity
      in vivo.

PMID- 24561670
TI  - Synthesis and study of cytotoxic activity of 1,2,4-trioxane- and egonol-derived
      hybrid molecules against Plasmodium falciparum and multidrug-resistant human
      leukemia cells.
AB  - Malaria and cancer cause the death of millions of people every year. To combat
      these two diseases, it is important that new pharmaceutically active compounds
      have the ability to overcome multidrug resistance in cancer and Plasmodium
      falciparum strains. In search of effective anti-cancer and anti-malaria hybrids
      that possess improved properties compared to their parent compounds, a series of
      novel 1,2,4-trioxane-based hybrids incorporating egonol and/or ferrocene
      fragments were synthesized and tested in vitro against P. falciparum strains,
      CCRF-CEM cells and the multidrug-resistant P-glycoprotein-over-expressing
      CEM/ADR5000 cells. The most active compounds against P. falciparum strains were
      artesunic acid homodimers 12 and 13 (IC50 of 0.32 and 0.30 nM, respectively),
      whereas novel hybrids 7 (1,2,4-trioxane-ferrocene-egonol), 9 (1,2,4-trioxane
      ferrocene) and 11 (artesunic acid-egonol) showed a remarkable cytotoxicity toward
      CCRF-CEM cells (IC50 of 0.07, 0.25 and 0.18 MUM, respectively). A cooperative and
      synergistic effect of the three moieties 1,2,4-trioxane, ferrocene and egonol in
      hybrid molecule 7 is significant and is obviously stronger than in hybrids 9
      (1,2,4-trioxane-ferrocene) and 11 (artesunic acid-egonol), which comprises of
      only two of the three considered parent compounds. Interestingly, hybrid 9
      containing a 1,2,4-trioxane and a ferrocene fragment has shown to be the most
      effective among the studied hybrids against the tested multidrug-resistant
      leukemia CEM/ADR5000 cells (IC50 of 0.57 MUM) and possesses a degree of cross
      resistance of 2.34.

PMID- 24561671
TI  - Chemical genetics-based discovery of indole derivatives as HCV NS5B polymerase
      inhibitors.
AB  - In order to identify the inhibitors of hepatitis C virus (HCV) replication with a
      novel scaffold via a mechanistically unbiased approach, we screened our in-house
      library composed of ~6000 compounds with various chemical structures by using the
      renilla luciferase-linked genotype 2a reporter virus, and we identified a series
      of compounds containing an indole moiety that were active against HCV
      replication. Based on this result, we further synthesized three groups of indole
      derivatives and evaluated their inhibitory effects on HCV replication. In the
      present structure-activity relationship study of these indole derivatives, we
      discovered that compound 12e was the most potent inhibitor of HCV replication
      with minimal cytotoxicity (EC50 = 1.1 MUM, EC90 = 2.1 MUM, and CC50 = 61.8 MUM).
      We also confirmed that compound 12e caused a dose- and time-dependent reduction
      of viral RNA as well as viral protein levels in both genotype 2a J6/JFH1 RNA
      transfected cells and genotype 1b Bart79I subgenomic replicon cells. Finally, a
      genetic mapping study of mutant viruses resistant to compound 12e revealed that
      NS5B RNA polymerase was the potential target. This finding was further validated
      by demonstration of inhibition of NS5B RNA polymerase in vitro by compound 12e
      (IC50 = 292 nM). Compound 12e may serve as a valuable candidate for the
      development of a new class of HCV NS5B RNA polymerase inhibitors in the future.

PMID- 24561672
TI  - Development of GoSlo-SR-5-69, a potent activator of large conductance Ca2+
      activated K+ (BK) channels.
AB  - We have designed, synthesised and characterised the effects of a number of novel
      anthraquinone derivatives and assessed their effects on large conductance, Ca(2+)
      activated K(+) (BK) channels recorded from rabbit bladder smooth muscle cells
      using the excised, inside/out configuration of the patch clamp technique. These
      compounds are members of the GoSlo-SR family of compounds, which potently open BK
      channels and shift the voltage required for half maximal activation (V1/2)
      negatively. The efficacy of the anilinoanthraquinone derivatives was enhanced
      when the size of ring D was increased, since the cyclopentane and cyclohexane
      derivatives shifted the V1/2, by -24 +/- 6 mV and -54 +/- 8 mV, respectively,
      whereas the cycloheptane and cyclooctane derivatives shifted the V1/2 by -61 +/-
      6 mV and -106 +/- 6 mV. To examine if a combination of hydrophobicity and steric
      bulking of this region further enhanced their ability to open BK channels, we
      synthesised a number of naphthalene and tetrahydro-naphthalene derivatives. The
      tetrahydro-2-naphthalene derivative GoSlo-SR-5-69 was the most potent and
      efficacious of the series since it was able to shift the activation V1/2 by
      greater than -100 mV when applied at a concentration of 1 MUM and had an EC50 of
      251 nM, making it one of the most potent and efficacious BK channel openers
      synthesised to date.

PMID- 24561674
TI  - Synthesis and studies of anticancer properties of lupane-type triterpenoid
      derivatives containing a cisplatin fragment.
AB  - Both betulinic acid 1 and cisplatin are promising antitumor agents, which induce
      apoptotic cell death of cancer cells. In the present investigation a new series
      of betulinic acid-cisplatin conjugates were synthesized and cytotoxicity and
      selectivity were assessed against five different tumor cell lines. The aim was to
      combine two structural units, both related with apoptosis induction. The
      derivatives exerted a dose-dependent antiproliferative action at micromolar
      concentrations and the effect of these structural variations on anticancer
      activity was studied and discussed. Several compounds revealed significant
      antitumor activity, as the most active substance 3-O-acetylbetulinic (2-(2
      aminoethyl)aminoethyl)amide (IC50=1.30-2.24 MUM). Interestingly, Betulinic acid
      cisplatin conjugates were less cytotoxic than the precursors.

PMID- 24561673
TI  - Direct synthesis of 4-organylsulfenyl-7-chloro quinolines and their toxicological
      and pharmacological activities in Caenorhabditis elegans.
AB  - We describe herein our results on the synthesis and biological properties in
      Caenorhabditis elegans of a range of 4-organylsulfenyl-7-chloroquinolines. This
      class of compounds have been easily synthesized in high yields by direct reaction
      of 4,7-dichloroquinoline with organylthiols using DMSO as solvent at room
      temperature under air atmosphere and tolerates a range of substituents in the
      organylsulfenyl moiety. We have performed a toxicological and pharmacological
      screening of the synthesized 4-organylsulfenyl-7-chloroquinolines in vivo in C.
      elegans acutely exposed to these compounds, under per se and stress conditions.
      Hence, we determined the lethal dose 50% (LD50), in order to choose a nonlethal
      concentration (10 MUM) and verified that at that concentration some of the
      compounds depicted protective action against the induced damage inflicted by
      paraquat, a superoxide generator. Two compounds (3c and 3h) reduced the toxicity
      inflicted by paraquat above survival, reproduction and longevity of the worms, at
      least in part, by reducing the reactive oxygen species (ROS) generated by the
      toxicant exposure. Besides, these compounds increased the quantities of
      superoxide dismutase (SOD-3::GFP) and catalase (CTL-1,2,3::GFP), antioxidant
      enzymes. We concluded that the protective effects of the compounds observed in
      this study might have been a hormetic response dependent of the transcriptional
      factor DAF-16/FOXO, causing a non-lethal oxidative stress that protects against
      the subsequently damage induced by paraquat.

PMID- 24561675
TI  - Conformational restriction of aryl thiosemicarbazones produces potent and
      selective anti-Trypanosoma cruzi compounds which induce apoptotic parasite death.
AB  - Chagas disease, caused by Trypanosoma cruzi, is a life-threatening infection
      leading to approximately 12,000 deaths per year. T. cruzi is susceptible to
      thiosemicarbazones, making this class of compounds appealing for drug
      development. Previously, the homologation of aryl thiosemicarbazones resulted in
      an increase in anti-T. cruzi activity in comparison to aryl thiosemicarbazones
      without a spacer group. Here, we report the structural planning, synthesis and
      anti-T. cruzi evaluation of new aryl thiosemicarbazones (9a-x), designed as more
      conformationally restricted compounds. By varying substituents attached to the
      phenyl ring, substituents were observed to retain, enhance or greatly increase
      the anti-T. cruzi activity, in comparison to the nonsubstituted derivative. In
      most cases, hydrophobic and bulky substituents, such as bromo, biphenyl and
      phenoxyl groups, greatly increased antiparasitic activity. Specifically,
      thiosemicarbazones were identified that inhibit the epimastigote proliferation
      and were toxic for trypomastigotes without affecting mouse splenocytes viability.
      The most potent anti-T. cruzi thiosemicarbazones were evaluated against cruzain.
      However, inhibition of this enzyme was not observed, suggesting that the
      compounds work through another mechanism. In addition, examination of T. cruzi
      cell death showed that these thiosemicarbazones induce apoptosis. In conclusion,
      the structural design executed within the series of aryl thiosemicarbazones (9a
      x) led to the identification of new potent anti-T. cruzi agents, such as
      compounds (9h) and (9r), which greatly inhibited epimastigote proliferation, and
      demonstrated a toxicity for trypomastigotes, but not for splenocytes.
      Mechanistically, these compounds do not inhibit the cruzain, but induce T. cruzi
      cell death by an apoptotic process.

PMID- 24561677
TI  - Pt/ZnO nanoarray nanogenerator as self-powered active gas sensor with linear
      ethanol sensing at room temperature.
AB  - A self-powered gas sensor that can actively detect ethanol at room temperature
      has been realized from a Pt/ZnO nanoarray nanogenerator. Pt nanoparticles are
      uniformly distributed on the whole surface of ZnO nanowires. The piezoelectric
      output of Pt/ZnO nanoarrays can act not only as a power source, but also as a
      response signal to ethanol at room temperature. Upon exposure to dry air and 1500
      ppm ethanol at room temperature, the piezoelectric output of the device under the
      same compressive strain is 0.672 and 0.419 V, respectively. Moreover, a linear
      dependence of the sensitivity on the ethanol concentration is observed. Such a
      linear ethanol sensing at room temperature can be attributed to the atmosphere
      dependent variety of the screen effect on the piezoelectric output of ZnO
      nanowires, the catalytic properties of Pt nanoparticles, and the Schottky
      barriers at Pt/ZnO interfaces. The present results can stimulate research in the
      direction of designing new material systems for self-powered room-temperature gas
      sensing. 

PMID- 24561678
TI  - Unexpected diagnosis of peripheral schwannoma on 18F-fluoroethylcholine PET/CT
      for localization of prostate cancer recurrence and biopsy under real-time
      PET/ultrasound fusion guidance.
AB  - 18F-Fluoroethylcholine (18F-FEC) PET/CT is well established for the detection of
      prostate cancer recurrence. However, its specificity is sometimes impaired by
      false-positive findings. In the present case, atypical cancer recurrence in the
      right distal lower leg was suspected on 18F-FEC PET/CT in a patient with a
      history of prostate cancer and an increased prostate-specific antigen level.
      Using a real-time PET/ultrasound fusion technique, the tumor was localized and a
      biopsy carried out, leading to a final diagnosis of peripheral schwannoma.

PMID- 24561676
TI  - Structure-function relationships of Nile blue (EtNBS) derivatives as
      antimicrobial photosensitizers.
AB  - The benzophenothiazinium dye EtNBS has previously been tested as a
      photosensitizer to mediate photodynamic therapy (PDT). It has been employed to
      kill cancer cells and microbial cells in vitro and to treat tumors and infections
      in vivo. We synthesized a panel of derivatives substituted at the 1-position of
      the benzene ring with electron donating or electron withdrawing groups (amino,
      acetamido and nitro) and tested their production of reactive oxygen species (ROS)
      and light-mediated killing of two species of Gram-positive and two species of
      Gram-negative bacteria. All three compounds showed lower fluorescence, lower
      yield of ROS and less microbial killing than parent EtNBS, while the order of
      activity (nitro > amino > acetamido) showed that an electron withdrawing
      substituent was better than electron donating. To test the hypothesis that 1
      substitution distorts the planar structure of the conjugated rings we compared
      two compounds substituted with N-ethylpropylsulfonamido either at the 1-position
      or at the 4-position. The 4-isomer was significantly more photoactive than the 1
      isomer. We also prepared an EtNBS derivative with a guanidinium group attached to
      the 5-amino group. This compound had high activity against Gram-negative bacteria
      due to the extra positive charge. Cellular uptake of the compounds by the four
      bacterial species was also measured and broadly correlated with activity. These
      results provided three separate pieces of structure-activity relationship data
      for antimicrobial photosensitizers based on the EtNBS backbone.

PMID- 24561679
TI  - A rare case of metastatic clear cell carcinoma of the Mullerian system
      originating from the peritoneum assessed by 18F-FDG PET/CT.
AB  - We describe a rare case of metastatic Mullerian tumor originating from the
      peritoneum assessed by F-FDG PET/CT. A 52-year-old female patient underwent F-FDG
      PET/CT for metabolic characterization of a right pelvic lesion. PET/CT revealed
      increased F-FDG uptake corresponding to a 3-cm lesion located behind the right
      anterior pelvic wall. Furthermore, increased F-FDG uptake in a right external
      iliac lymph node was detected. Based on these F-FDG PET/CT findings, the patient
      underwent resection of the pelvic lesion and the right external iliac lymph node.
      Histology demonstrated a clear cell carcinoma of the Mullerian system originating
      from the peritoneum with lymph nodal metastasis. 

PMID- 24561680
TI  - Molecular imaging of late somatostatin receptor-positive metastases of renal cell
      carcinoma in the pancreas by 68Ga DOTATOC PET/CT: a rare differential diagnosis
      to multiple primary pancreatic neuroendocrine tumors.
AB  - Ga somatostatin receptor PET/CT, currently the most sensitive imaging modality
      for well-differentiated neuroendocrine tumors, is based on the molecular imaging
      of somatostatin receptors (SSTRs) that are expressed in different tumor entities
      such as neuroendocrine neoplasms, lymphomas, meningiomas, or renal cell cancer
      (RCC). Most neuroendocrine neoplasms show a high expression of SSTR subtypes 2A
      and 5, whereas the overexpression of SSTR2A in RCC is mainly seen in peritumoral
      vessels. Here we report a case with strongly SSTR-positive pancreatic lesions
      detected by Ga DOTATOC PET/CT, which histologically turned out to be ultralate
      metastases of a RCC. 

PMID- 24561681
TI  - PET in multiple sclerosis.
AB  - PET is a powerful in vivo functional imaging tool for investigating healthy and
      diseased brain. It provides noninvasive quantification of selected biological
      targets that could help build understanding of complex central nervous system
      disorders such as multiple sclerosis (MS). To date, in MS, PET could only offer
      complementary support to MRI studies because MRI has still a profound role in
      monitoring the clinical course of MS. However, recent developments in PET imaging
      offer the potential to assess the MS brain in vivo in a way that MRI is limited.
      PET in MS could be used for the investigation of underlying pathophysiology of
      neuroinflammation, neuronal dysfunction, and demyelination, and remyelination.
      Quantitative measures of molecular targets with PET could also have future uses
      in clinical trials of drug development. However, the use of PET is still limited
      because of the high costs of cyclotrons and radiochemical laboratories. Once
      these limitations are bypassed alongside advances in research, PET could help in
      the clinical practice of MS by providing a useful imaging tool for the accurate
      diagnosis, monitoring of clinical progression, and planning of treatment. 

PMID- 24561682
TI  - False-positive uptake of 124I in a laryngeal cyst mimicking thyroid remnant after
      thyroidectomy and 131i therapy for follicular thyroid carcinoma.
AB  - A 46-year-old woman underwent total thyroidectomy followed by I therapy for
      follicular thyroid carcinoma stage T3 N0 M0. Eleven years after diagnosis, the
      patient complained about voice changes and feared recurrent disease. Follow-up I
      PET/CT scan revealed focal uptake in the neck, in the absence of any anatomic
      substrate on CT. Physical examination including laryngoscopy did not show any
      tumor or signs of recurrent disease. MRI of the neck demonstrated an oval-shaped
      lesion in the right false vocal cord. The lesion was removed in toto using carbon
      dioxide laser. Histological examination demonstrated a benign cyst, and the
      patient recovered entirely. 

PMID- 24561683
TI  - Incidental 11C-choline PET/CT uptake due to esophageal carcinoma in a patient
      studied for prostate cancer.
AB  - A 75-years-old patient with a history of prostate cancer, previously treated with
      radical prostatectomy, underwent C-choline PET/CT for restaging due to a rise in
      the prostate-specific antigen level. The study revealed a focal uptake of C
      choline in the esophagus. A subsequent endoscopic examination showed the presence
      of an esophageal lesion, and after surgery, the histologic diagnosis was mildly
      differentiated squamous cell carcinoma. In our case, the incidental esophageal
      uptake revealed by C-choline PET/CT allowed the early diagnosis of an unsuspected
      esophageal carcinoma. 

PMID- 24561684
TI  - Unusual widespread metastatic subcutaneous lesions in a patient with ileal
      carcinoid evidenced by 68Ga-DOTATOC PET/CT.
AB  - 68Ga-DOTATOC PET/CT has been widely validated in diagnosis and follow-up of
      carcinoid. A 47-year-old woman with ileal carcinoid underwent a 68Ga-DOTATOC
      PET/CT for restaging purposes. Images showed extensive liver involvement and also
      a widespread metastatic subcutaneous metastases in the right chest wall and in
      the right laterocervical region. The presence of multiple soft-tissue metastases,
      as described in our case and imaged with 68Ga-DOTATOC, represents a very rare
      clinical entity.

PMID- 24561685
TI  - 18F-FDG uptake in multiple splenic foci on PET/CT: an unusual case of visceral
      leishmaniasis.
AB  - A previously well 48-year-old male patient presented with several months of
      weight loss, fever, massive hepatosplenomegaly, and pancytopenia. A provisional
      diagnosis of lymphoma could not be confirmed on blind lymph node or bone marrow
      biopsies. Referral for 18F-FDG PET was made to identify an appropriate biopsy
      site. Focal uptake in multiple splenic lesions was seen, with normal FDG uptake
      elsewhere in the body. Splenectomy was then performed and histology revealed
      leishmaniasis, with no evidence of lymphoma. Focally FDG avid splenic deposits
      have never been reported in leishmaniasis and were likely due to nodular red pulp
      expansion.

PMID- 24561686
TI  - 18F-FDG PET/CT metabolic variability in functioning oncocytic parathyroid adenoma
      with brown tumors.
AB  - A 29-year-old female patient exhibited a solitary neck mass, severe
      hypercalcemia, and multiple skeletal lytic lesions consistent with metastatic
      neoplastic disease. Fine-needle aspiration (FNA) cytology of the neck lesion
      indicated a follicular thyroid neoplasm. CT-guided bone biopsy was non
      diagnostic. Subsequent 18F-FDG PET/CT examination demonstrated avid glucose
      uptake within the neck mass and diffuse bony lesions of variable metabolic
      activity. Repeat biopsy utilizing PET/CT guidance produced core tissue with
      classic histologic features of a brown tumor. Postoperative histology revealed an
      exclusively oncocytic parathyroid adenoma. Atypical radiotracer uptake of this
      rare functioning adenoma subtype is illustrated with discussion of improved
      procedural diagnostic yield utilizing PET/CT.

PMID- 24561687
TI  - Distant metastases in a young woman with Stewart-Treves syndrome demonstrated by
      an FDG-PET/CT scan.
AB  - This 17-year-old woman had chronic congenital lymphedema in the left lower
      extremity since childhood. She underwent surgeries to remove excessive
      lymphedematous tissues more than 15 times previously. Histopathology of the
      specimen from the recent surgery revealed angiosarcoma; therefore, FDG-PET/CT
      scan was arranged to determine the extent of tumor spread, and distant metastases
      were discovered. Stewart-Treves syndrome is angiosarcomas that arise secondary to
      chronic lymphedema. Because of the high lethality of this condition, the FDG
      PET/CT scan may be a clinically useful imaging modality to detect the possible
      malignant transformation earlier for patients with chronic lymphedema. 

PMID- 24561688
TI  - Imaging myocardium at risk and coronary inflammation in non-ST-segment elevation
      myocardial infarction: combined use of FDG PET and optical coherence tomography.
AB  - Patients with non-ST-segment elevation myocardial infarction (NSTEMI) represent a
      heterogeneous group in terms of jeopardized myocardium, pathogenetic mechanisms,
      and risk of recurrent events. In particular, estimation of myocardium at risk may
      be challenging before angiography. Yet the mechanisms leading to coronary
      instability underlying acute coronary syndromes (ACS) have not been completely
      elucidated. In this report (figure), we describe the potential utility of FDG PET
      in defining the myocardium at risk and to unravel coronary inflammation in one
      NSTEMI patient with normal level of C-reactive protein. Optical coherence
      tomography (OCT) images of culprit lesions are also shown. 

PMID- 24561689
TI  - 18F-FDG PET/CT in a case of multifocal skeletal tuberculosis without pulmonary
      disease and potential role for monitoring treatment response.
AB  - A 39-year-old man presented with left shoulder and interscapular pain. 99mTc-MDP
      bone scan demonstrated multiple active bone lesions including scapula, spines,
      ribs, and pelvis. Chest X-ray showed no active lung lesion, and MRI demonstrated
      infiltrative enhancing lesions in the T-spines and ribs, indicating skeletal
      metastasis. 18F-FDG PET/CT performed to search for hidden malignancy revealed
      multiple osteolytic lesions with intense FDG uptake, supporting metastasis.
      Tissue obtained from the T1 lesion showed no malignant cells but was positive for
      Mycobacterium tuberculosis. After 18 months of antituberculosis medication,
      follow-up 18F-FDG PET/CT showed complete normalization of FDG uptake in the
      skeletal lesions.

PMID- 24561690
TI  - Unusual metastases of thyroid cancer to mediastinal blood vessels.
AB  - Poorly differentiated thyroid cancer is a rare thyroid cancer, accounts for
      approximately 5% of all thyroid cancer cases, and is associated with a poor
      prognosis. It commonly metastasizes to regional lymph nodes, lung, and bones. We
      present a patient with poorly differentiated thyroid cancer with unusual
      extensive spread to mediastinal blood vessels. 

PMID- 24561691
TI  - Tips for a physician in getting the right job, Part IX: Interview questions for
      any physician job applicant.
AB  - There are many common questions and requests, which physician applicants for
      either a clinical or executive position are likely to encounter on a job
      interview. This article enumerates many of these and offers hints on preparation
      and having winning answers. 

PMID- 24561692
TI  - Sentinel lymph node mapping in melanoma: the issue of false-negative findings.
AB  - Management of cutaneous melanoma has changed after introduction in the clinical
      routine of sentinel lymph node biopsy (SLNB) for nodal staging. By defining the
      nodal basin status, SLNB provides a powerful prognostic information.
      Nevertheless, some debate still surrounds the accuracy of this procedure in terms
      of false-negative rate. Several large-scale studies have reported a relatively
      high false-negative rate (5.6%-21%), correctly defined as the proportion of false
      negative results with respect to the total number of "actual" positive lymph
      nodes. In this review, we identified all the technical aspects that the nuclear
      medicine physician, the surgeon, and the pathologist should take into account to
      improve accuracy of the procedure and minimize the false-negative rate. In
      particular, SPECT/CT imaging detects more SLNs than those found by planar
      lymphoscintigraphy. Furthermore, the nuclear medicine community should reach a
      consensus on the radioactive counting rate threshold to better guide the surgeon
      in identifying the lymph nodes with the highest likelihood of housing metastases
      ("true biologic SLNs"). Analysis of the harvested SLNs by conventional techniques
      is also a further potential source for error. More accurate SLN analysis (eg,
      molecular analysis by reverse transcriptase-polymerase chain reaction) and more
      extensive SLN sampling identify more positive nodes, thus reducing the false
      negative rate.The clinical factors identifying patients at higher-risk local
      recurrence after a negative SLNB include older age at diagnosis, deeper lesions,
      histological ulceration, and head-neck anatomic location of the primary
      lesion.The clinical impact of a false-negative SLNB on the prognosis of melanoma
      patients remains controversial, because the majority of studies have failed to
      demonstrate overall statistically significant disadvantage in melanoma-specific
      survival for false-negative SLNB patients compared with true-positive SLNB
      patients.When new more effective drugs will be available in the adjuvant setting
      for stage III melanoma patients, the implication of an accurate staging procedure
      for the sentinel lymph nodes will be crucial for both patients and clinicians.
      Standardization and accuracy of SLN identification, removal, and analysis are
      required. 

PMID- 24561693
TI  - [Synopsis on clinical practice guideline of gastric cancer in Korea: an evidence
      based approach].
AB  - Although, gastric cancer is quite common in Korea, the treatment outcome is
      relatively favorable compared to that of Western countries. However, there is no
      Korean multidisciplinary guideline for gastric cancer and thus, a guideline
      adequate for domestic circumstances is required. Experts from related societies
      developed 22 recommendation statements for the diagnosis (n=9) and treatment
      (n=13) based on relevant key questions. Evidence levels based on systematic
      review of literatures were classified as five levels from A to E, and
      recommendation grades were classified as either strong or weak. The topics of
      this guideline cover diagnostic modalities (endoscopy, endoscopic ultrasound,
      radiologic diagnosis), treatment modalities (surgery, therapeutic endoscopy,
      chemotherapy, radiotherapy) and pathologic evaluation. External review of the
      guideline was conducted at the finalization phase.

PMID- 24561694
TI  - [Trends in the eradication rates of Helicobacter pylori infection in Daegu and
      Gyeongsangbuk-do, Korea: multicenter study over 13 years].
AB  - BACKGROUND/AIMS: The eradication rates of Helicobacter pylori infection have been
      reported to have decreased over the years due to antibiotics resistance. The aim
      of this study is to investigate the trend of eradication rates of first-line
      triple therapy for H. pylori over the past 13 year period, and to evaluate
      factors affecting H. pylori eradication in Daegu and Gyeongsangbuk-do, Korea.
      METHODS: A total of 2,982 patients with H. pylori infection who were treated with
      either 1 week or 2 weeks first-line therapy (proton pump inhibitor [PPI],
      amoxicillin, and clarithromycin) from January 1999 through December 2011 were
      included in this study. Data were collected by retrospectively reviewing the
      medical records. RESULTS: The overall H. pylori eradication rate was 87.2%. The
      eradication rates from 1999 to 2011 fluctuated between 78.0% and 95.7%, but no
      definite evidence of a decreasing tendency was seen over the 13 year period
      (p=0.113). Furthermore, there was no significant difference in the eradication
      rate according to the duration of therapy (p=0.592). However, there was a
      significant difference in the eradication rate among various PPIs (p<0.01).
      CONCLUSIONS: There was no decreasing trend in the H. pylori eradication rate over
      the past 13 years in Daegu and Gyeongsangbuk-do, Korea. There also was no
      difference in the eradication rates depending on duration of therapy. However, a
      significant difference was noted among various PPIs.

PMID- 24561695
TI  - [Comparison on the long term outcome between endoscopic submucosal dissection and
      surgical treatment for undifferentiated early gastric cancer].
AB  - BACKGROUND/AIMS: There are controversies on the efficacy and safety of endoscopic
      submucosal dissection (ESD) for un-differentiated early gastric cancer (EGC)
      despite the expansion of ESD indications. The aim of this study was to evaluate
      the long term outcome of ESD compared to that of surgical treatment in patients
      with undifferentiated EGC. METHODS: A total of 76 patients who underwent ESD for
      undifferentiated EGC and 149 patients who met the ESD indication and received
      surgical treatment from January 2005 to December 2010 at Chonnam National
      University Hwasun Hospital were included. RESULTS: In the ESD group, en bloc
      resection and complete resection were achieved in 84.2% (64/76) and 76.3% (58/76)
      of patients, respectively. Among these patients, 58 (76.3%) met the ESD
      indication (indication group), and the remaining 18 (23.7%) did not meet the ESD
      indication (above indication group). Complete resection rates for indication
      group and above indication group were 86.2% (50/58) and 44.4% (8/18),
      respectively (p<0.05). The mean follow-up period was 42.2 +/- 19.2 months. Total
      recurrence rates in the ESD group and operation group were 14.1% (9/76) and 0.7%
      (1/149), respectively (p<0.05). The main complication of ESD was bleeding (5.2%,
      4/76). In the operation group, 2 (1.3%) patients died from postoperative bleeding
      and leakage of anastomosis site. CONCLUSIONS: ESD may be a feasible and safe
      treatment modality compared to that of surgical treatment for undifferentiated
      EGC when managed according to the expanded criteria. However, close endoscopic
      surveillance is required in this group because of higher incidence of
      intragastric recurrence.

PMID- 24561696
TI  - [Efficacy of feeding pump for patients on enteral tube feeding: a systematic
      literature review and analysis].
AB  - BACKGROUND/AIMS: This study was conducted to establish a guideline on the
      utilizing of feeding pump in patients requiring enteral tube feeding. METHODS: As
      a first step, textbooks on nutrition and guidelines from regional clinical
      nutrition societies were analyzed. Afterwards, data on the efficacy, safety, and
      practicality of feeding pump application were collected and evaluated by
      systematically reviewing the related literature. As data sources, 8 domestic
      databases including KoreaMed and global databases such as Ovid-MEDLINE, Ovid
      EMBASE, and Cochrane Library were utilized. A total of 2,016 related articles was
      selected by applying the keyword "(enteral feeding.mp AND pump.mp)". RESULTS:
      Textbooks and guidelines were not able to draw conclusions on the effects of the
      feeding pump because the injection speed, tube size, and etcetera were different
      for enteral feeding. Feeding pump assisted enteral tube feeding was an efficient,
      safe, and practical procedure for reducing maladjustment-related complications of
      enteral tube feeding, which are obvious obstacles for maintaining nutritional
      balances in patients requiring tube feeding. CONCLUSIONS: Feeding pump
      application can be considered an efficient and safe measure that is acceptable in
      patients on small intestinal tube feeding, critically-ill patients on gastro
      intestinal tube feeding, premature babies, and critically-ill or severely
      malnourished children (recommendation grade D).

PMID- 24561697
TI  - [Clinical usefulness of bile cytology obtained from biliary drainage tube for
      diagnosing cholangiocarcinoma].
AB  - BACKGROUND/AIMS: Biliary drainage is performed in many patients with
      cholangiocarcinoma (CCA) to relieve obstructive jaundice. For those who have
      undergone biliary drainage, bile cytology can be easily performed since the
      access is already achieved. This study aims to determine the clinical usefulness
      of bile cytology for the diagnosis of CCA and to evaluate factors affecting its
      diagnostic yield. METHODS: A total of 766 consecutive patients with CCA underwent
      bile cytology via endoscopic nasobiliary drainage or percutaneous transhepatic
      biliary drainage from January 2000 to June 2012. Data were collected by
      retrospectively reviewing the medical records. We evaluated the diagnostic yield
      of bile cytology with/without other sampling methods including brush cytology and
      endobiliary forcep biopsy, and the optimal number of repeated bile sampling.
      Several factors affecting diagnostic yield were then analyzed. RESULTS: The
      sensitivity of bile cytology, endobiliary forceps biopsy, and a combination of
      both sampling methods were 24.7% (189/766), 74.4% (259/348), and 77.9% (271/348),
      respectively. The cumulative positive rate of bile sampling increased from 40.7%
      (77/189) at first sampling to 93.1% (176/189) at third sampling. On multivariate
      analysis, factors associated with positive bile cytology were perihilar tumor
      location, intraductal growing tumor type, tumor extent >= 20 mm, poorly
      differentiated grade tumor, and three or more samplings. CONCLUSIONS: Although
      bile cytology itself has a low sensitivity in diagnosing CCA, it has an additive
      role when combined with endobiliary forceps biopsy. Due to the relative ease and
      low cost, bile cytology can be considered a reasonable complementary diagnostic
      tool for diagnosing CCA.

PMID- 24561698
TI  - Endoscopic resection as a possible radical treatment for duodenal gangliocytic
      paraganglioma: a report of four cases.
AB  - Gangliocytic paraganglioma (GP) is a rare, benign tumor which is usually found in
      the duodenum. We here report four recent cases of GP, with successful endoscopic
      resection in three cases, including a lesion on the ampulla of Vater. In all
      cases, each lesion had a stalk that facilitated removal using an endoscopic
      approach. Endoscopic mucosal resection is a feasible and safe treatment if the
      location, depth, and lymph node status are all favorable and is also helpful for
      definite diagnosis of unknown duodenal mass. To avoid morbidity resulting from
      open surgical resection, careful inspection for the peduncle of the GP will help
      determine the feasibility of endoscopic resection.

PMID- 24561699
TI  - Two cases of uncommon complication during percutaneous endoscopic gastrostomy
      tube replacement and treatment.
AB  - We presented two interesting cases of gastrocolocutaneous fistula that occurred
      after percutaneous endoscopic gastrostomy (PEG) tube placement, and its
      management. This fistula is a rare complication that occurs after PEG insertion,
      which is an epithelial connection between mucosa of the stomach, colon, and skin.
      The management of the fistula is controversial, ranging from conservative to
      surgical intervention. Endoscopists should be aware of the possibility of
      gastrocolocutaneous fistula after PEG insertion, and should evaluate the risk
      factors that may contribute to the development of gastrocolocutaneous fistula
      before the procedure. We reviewed complications of gastrostomy tube insertion,
      symptoms of gastrocolocutaneous fistula, and its risk factors.

PMID- 24561700
TI  - A case of colonic pseudoobstruction related to bacterial overgrowth due to a
      sigmoidocecal fistula.
AB  - Colocolic fistulas are usually a complication of an inflammatory or neoplastic
      process. Development of these abnormal bowel communications may lead to bacterial
      overgrowth. We report on a 71-year-old man with a one-year history of recurrent
      abdominal distension and irregular bowel habits. Abdominal X-rays and computed
      tomography showed multiple air-fluid levels and loops of distended bowel without
      evidence of mechanical obstruction or diverticulitis. Colonoscopy showed a
      fistulous tract between the sigmoid colon and cecum. Results of a lactulose
      breath test showed high fasting breath CH4 levels, which were thought to be the
      result of intestinal bacterial overgrowth. The patient was diagnosed with a
      colonic pseudo-obstruction associated with bacterial overgrowth due to a
      sigmoidocecal fistula. We recommended surgical correction of the sigmoidocecal
      fistula; however, the patient requested medical treatment. After antibiotic
      therapy, the patient still had mild symptoms but no acute exacerbations.

PMID- 24561701
TI  - [Synchronous malignant intraductal papillary mucinous neoplasms of the bile duct
      and pancreas requiring left hepatectomy and total pancreatectomy].
AB  - Intraductal papillary mucinous neoplasm of the bile duct (IPMN-B) and intraductal
      papillary mucinous neoplasm of the pancreas (IPMN-P) have striking similarities
      and are recognized as counterparts. However, simultaneous occurrence of IPMN-B
      and IPMN-P is extremely rare. A 66 year-old female presented with recurrent
      epigastric pain and fever. During the past 9 years, she had three clinical
      episodes related to intrahepatic duct stones and IPMN-P in the pancreas head and
      was managed by medical treatment. Laboratory test results at admission revealed
      leukocytosis (12,600/mm(3)) and elevated CA 19-9 level (1,200 U/mL). Imaging
      study demonstrated liver abscess in the Couinaud's segment 4, IPMN-B in the left
      lobe, and IPMN-P in the whole pancreas with suspicious malignant change. Liver
      abscess was drained preoperatively, followed by left lobectomy with bile duct
      resection and total pancreatectomy with splenectomy. On histologic examination,
      non-invasive intraductal papillary mucinous carcinoma arising from various degree
      of dysplastic mucosa of the liver and pancreas could be observed. However, there
      was no continuity between the hepatic and pancreatic lesions. This finding in our
      case supports the theory that double primary lesions are more likely explained by
      a diffuse IPMN leading to synchronous tumors arising from both biliary and
      pancreatic ducts rather than by a metastatic process. Herein we present a case of
      simultaneous IPMN of the bile duct and pancreas which was successfully treated by
      surgical management.

PMID- 24561702
TI  - A noninvasive method for in situ determination of mating success in female
      American lobsters (Homarus americanus).
AB  - Despite being one of the most productive fisheries in the Northwest Atlantic,
      much remains unknown about the natural reproductive dynamics of American
      lobsters. Recent work in exploited crustacean populations (crabs and lobsters)
      suggests that there are circumstances where mature females are unable to achieve
      their full reproductive potential due to sperm limitation. To examine this
      possibility in different regions of the American lobster fishery, a reliable and
      noninvasive method was developed for sampling large numbers of female lobsters at
      sea. This method involves inserting a blunt-tipped needle into the female's
      seminal receptacle to determine the presence or absence of a sperm plug and to
      withdraw a sample that can be examined for the presence of sperm. A series of
      control studies were conducted at the dock and in the laboratory to test the
      reliability of this technique. These efforts entailed sampling 294 female
      lobsters to confirm that the presence of a sperm plug was a reliable indicator of
      sperm within the receptacle and thus, mating. This paper details the methodology
      and the results obtained from a subset of the total females sampled. Of the 230
      female lobsters sampled from George's Bank and Cape Ann, MA (size range = 71-145
      mm in carapace length), 90.3% were positive for sperm. Potential explanations for
      the absence of sperm in some females include: immaturity (lack of physiological
      maturity), breakdown of the sperm plug after being used to fertilize a clutch of
      eggs, and lack of mating activity. The surveys indicate that this technique for
      examining the mating success of female lobsters is a reliable proxy that can be
      used in the field to document reproductive activity in natural populations. 

PMID- 24561703
TI  - Pharmacokinetic evaluation of lisinopril-tryptophan, a novel C-domain ACE
      inhibitor.
AB  - Angiotensin-converting enzyme (ACE, EC 3.4.15.1) is a metallopeptidase comprised
      of two homologous catalytic domains (N- and C-domains). The C-domain cleaves the
      vasoactive angiotensin II precursor, angiotensin I, more efficiently than the N
      domain. Thus, C-domain-selective ACE inhibitors have been designed to investigate
      the pharmacological effects of blocking the C-terminal catalytic site of the
      enzyme and improve the side effect profile of current ACE inhibitors. Lisinopril
      tryptophan (LisW-S), an analogue of the ACE inhibitor lisinopril, is highly
      selective for the C-domain. In this study, we have analysed the ex vivo domain
      selectivity and pharmacokinetic profile of LisW-S. The IC50 value of LisW-S was
      38.5 nM in rat plasma using the fluorogenic substrate Abz-FRKP(Dnp)P-OH. For the
      pharmacokinetics analysis of LisW-S, a sensitive and selective LC-MS/MS method
      was developed and validated to determine the concentration of LisW-S in rat
      plasma. LisW-S was administered to Wistar rats at a dose of 1 mg/kg bodyweight
      intravenously, 5 mg/kg bodyweight orally. The Cmax obtained following oral
      administration of the drug was 0.082 MUM and LisW-S had an apparent terminal
      elimination half-life of around 3.1 h. The pharmacokinetic data indicate that the
      oral bioavailability of LisW-S was approximately 5.4%. These data provide a basis
      for better understanding the absorption mechanism of LisW-S and evaluating its
      clinical application.

PMID- 24561704
TI  - Drug delivery by tattooing to treat cutaneous leishmaniasis.
AB  - This study establishes a proof-of-concept that a tattoo device can target intra
      dermal drug delivery against cutaneous leishmaniasis (CL). The selected drug is
      oleylphosphocholine (OlPC) formulated as liposomes, particles known to be prone
      to macrophage ingestion. We first show that treatment of cultured Leishmania
      infected macrophages with OlPC-liposomes results in a direct dose-dependent
      killing of intracellular parasites. Based on this, in vivo efficacy is
      demonstrated using a 10 day tattooing-mediated treatment in mice infected with L.
      major and L. mexicana. In both models this regimen results in rapid clinical
      recovery with complete regression of skin lesions by Day 28. Parasite counts and
      histopathology examination confirm high treatment efficacy at the parasitic
      level. Low amount of drug required for tattooing combined with fast clinical
      recovery may have a positive impact on CL patient management. This first example
      of tattoo-mediated drug delivery could open to new therapeutic interventions in
      the treatment of skin diseases. 

PMID- 24561705
TI  - Lactate and the injured brain: friend or foe?
AB  - PURPOSE OF REVIEW: Energy metabolism is increasingly recognized as a key factor
      in the pathogenesis of acute brain injury (ABI). We review the role of cerebral
      lactate metabolism and summarize evidence showing that lactate may act as
      supplemental fuel after ABI. RECENT FINDINGS: The role of cerebral lactate has
      shifted from a waste product to a potentially preferential fuel and signaling
      molecule. According to the astrocyte-neuron lactate shuttle model, glycolytic
      lactate might act as glucose-sparing substrate. Lactate also is emerging as a key
      signal to regulate cerebral blood flow (CBF) and a neuroprotective agent after
      experimental ABI. Clinical investigation using cerebral microdialysis shows the
      existence of two main lactate patterns, ischemic - from anaerobic metabolism -
      and nonischemic, from activated glycolysis, whereby lactate can be used as
      supplemental energy fuel. Preliminary clinical data suggests hypertonic lactate
      solutions improve cerebral energy metabolism and are an effective treatment for
      elevated intracranial pressure (ICP) after ABI. SUMMARY: Lactate can be a
      supplemental fuel for the injured brain and is important to regulate glucose
      metabolism and CBF. Exogenous lactate supplementation may be neuroprotective
      after experimental ABI. Recent clinical data from ABI patients suggest hypertonic
      lactate solutions may be a valid therapeutic option for secondary energy
      dysfunction and elevated ICP.

PMID- 24561706
TI  - Feeding the gut: how, when and with what -- the metabolic issue.
AB  - PURPOSE OF REVIEW: To review the literature on feeding critically ill patients
      with special emphasis on the intestine. RECENT FINDINGS: Many dogmas have been
      questioned in the past few years. In particular, the absence of evidence for
      impact on outcomes in critically ill patients has been highlighted. So 'early
      enteral feeding', the trophic effect on intestinal mucosa in humans, 'pharmaco
      nutrition', postpyloric feeding and prokinetic drugs have all been found to lack
      proper evidence to affect outcomes. SUMMARY: The use of gastric feeding in
      critical illness is recommended. Successful gastric feeding is indicative of a
      functional gastrointestinal tract. Pharmacological effects of nutrients are
      questionable, but supplementation of deficits (glutamine, selenium, etc.) may be
      in the patient's best interest. A more individualized prescription of nutrition
      in the critically ill is advocated.

PMID- 24561707
TI  - Apocrine carcinoma arising in a complex fibroadenoma: a case report.
AB  - A carcinoma arising in a fibroadenoma is a rare event, which often entails a
      diagnostic challenge. The most common type is the lobular carcinoma and secondary
      a ductal carcinoma. We present an extremely rare case of malignant development of
      an invasive apocrine carcinoma in a complex fibroadenoma and underline the
      importance for clinicians to recognize the possibility of benign and malignant co
      existence especially in older women. 

PMID- 24561709
TI  - Development and characterization of novel electrically conductive PANI-PGS
      composites for cardiac tissue engineering applications.
AB  - Cardiovascular diseases, especially myocardial infarction, are the leading cause
      of morbidity and mortality in the world, also resulting in huge economic burdens
      on national economies. A cardiac patch strategy aims at regenerating an infarcted
      heart by providing healthy functional cells to the injured region via a carrier
      substrate, and providing mechanical support, thereby preventing deleterious
      ventricular remodeling. In the present work, polyaniline (PANI) was doped with
      camphorsulfonic acid and blended with poly(glycerol-sebacate) at ratios of 10, 20
      and 30vol.% PANI content to produce electrically conductive composite cardiac
      patches via the solvent casting method. The composites were characterized in
      terms of their electrical, mechanical and physicochemical properties. The in
      vitro biodegradability of the composites was also evaluated. Electrical
      conductivity increased from 0Scm(-1) for pure PGS to 0.018Scm(-1) for 30vol.%
      PANI-PGS samples. Moreover, the conductivities were preserved for at least 100h
      post fabrication. Tensile tests revealed an improvement in the elastic modulus,
      tensile strength and elasticity with increasing PANI content. The degradation
      products caused a local drop in pH, which was higher in all composite samples
      compared with pure PGS, hinting at a buffering effect due to the presence of
      PANI. Finally, the cytocompatibility of the composites was confirmed when C2C12
      cells attached and proliferated on samples with varying PANI content.
      Furthermore, leaching of acid dopants from the developed composites did not have
      any deleterious effect on the viability of C2C12 cells. Taken together, these
      results confirm the potential of PANI-PGS composites for use as substrates to
      modulate cellular behavior via electrical stimulation, and as biocompatible
      scaffolds for cardiac tissue engineering applications.

PMID- 24561708
TI  - Functionalizable hydrogel microparticles of tunable size and stiffness for soft
      tissue filler applications.
AB  - Particle size, stiffness and surface functionality are important in determining
      the injection site, safety and efficacy of injectable soft-tissue fillers.
      Methods to produce soft injectable biomaterials with controlled particle
      characteristics are therefore desirable. Here we report a method based on
      suspension photopolymerization and semi-interpenetrating network (semi-IPN) to
      synthesize soft, functionalizable, spherical hydrogel microparticles (MP) of
      independently tunable size and stiffness. MP were prepared using acrylated forms
      of polyethylene glycol (PEG), gelatin and hyaluronic acid. Semi-IPN MP of PEG
      diacrylate and PEG were used to study the effect of process parameters on
      particle characteristics. The process parameters were systematically varied to
      produce MP with size ranging from 115 to 515MUm and stiffness ranging from 190 to
      1600Pa. In vitro studies showed that the MP thus prepared were cytocompatible.
      The ratio and identity of the polymers used to make the semi-IPN MP were varied
      to control their stiffness and to introduce amine groups for potential
      functionalization. Slow-release polymeric particles loaded with Rhodamine or
      dexamethasone were incorporated in the MP as a proof-of-principle of drug
      incorporation and release from the MP. This work has implications in preparing
      injectable biomaterials of natural or synthetic polymers for applications as soft
      tissue fillers.

PMID- 24561710
TI  - Enzymatic conjugation of a bioactive peptide into an injectable hyaluronic acid
      tyramine hydrogel system to promote the formation of functional vasculature.
AB  - In this study, one-step enzyme-mediated preparation of a multi-functional
      injectable hyaluronic-acid-based hydrogel system is reported. Hydrogel was formed
      through the in situ coupling of phenol moieties by horseradish peroxidase (HRP)
      and hydrogen peroxide (H2O2), and bioactive peptides were simultaneously
      conjugated into the hydrogel during the gel formation process. The preparation of
      this multi-functional hydrogel was made possible by synthesizing peptides
      containing phenols which could couple with the phenol moieties of hyaluronic-acid
      tyramine (HA-Tyr) during the HRP-mediated crosslinking reaction. Preliminary
      studies demonstrated that two phenol moieties per molecule resulted in a
      consistently high degree of conjugation into the HA-Tyr hydrogel network, unlike
      the one modified with one phenol moiety per molecule. Therefore, an Arg-Gly-Asp
      (RGD) peptide bearing two phenol moieties (phenol2-poly(ethylene glycol)-RGD) was
      designed for conjugation to endow the HA-Tyr hydrogel with adhesion signals and
      enhance its bioactivities. Human umbilical vein endothelial cells (HUVECs)
      cultured on or within the RGD-modified hydrogels showed significantly different
      adhesion behavior, from non-adherence on the HA-Tyr hydrogel to strong adhesion
      on hydrogels modified with phenol2-poly(ethylene glycol)-RGD. This altered cell
      adhesion behavior led to improved cell proliferation, migration and formation of
      capillary-like network in the hydrogel in vitro. More importantly, when HUVECs
      and human fibroblasts (HFF1) were encapsulated together in the RGD-modified HA
      Tyr hydrogel, functional vasculature was observed inside the cell-laden gel after
      2weeks in the subcutaneous tissue. Taken together, the in situ conjugation of
      phenol2-poly(ethylene glycol)-RGD into HA-Tyr hydrogel system, coupled with the
      ease of incorporating cells, offers a simple and effective means to introduce
      biological signals for preparation of multi-functional injectable hydrogels for
      tissue engineering application.

PMID- 24561711
TI  - Highly porous and mechanically robust polyester poly(ethylene glycol) sponges as
      implantable scaffolds.
AB  - The development of suitable scaffolds plays a significant role in tissue
      engineering research. Although scaffolds with promising features have been
      produced via a variety of innovative methods, there are no fully synthetic tissue
      engineering scaffolds that possess all the desired properties in one three
      dimensional construct. Herein, we report the development of novel polyester
      poly(ethylene glycol) (PEG) sponges that display many of the desirable scaffold
      characteristics. Our novel synthetic approach utilizes acidchloride/alcohol
      chemistry, whereby the reaction between a hydroxyl end-functionalized 4-arm PEG
      and sebacoyl chloride resulted in cross-linking and simultaneous hydrogen
      chloride gas production, which was exploited for the in situ formation of highly
      interconnected pores. Variation of the fabrication conditions, including the
      precursor volume and concentration, allowed the pore size and structure as well
      as the compressive properties to be tailored. The sponges were found to possess
      excellent elastic properties, preserving their shape even after 80% compressive
      strain without failure. The benign properties of the sponges were demonstrated in
      an in vivo subcutaneous rat model, which also revealed uniform infiltration of
      vascularized tissue by 8 weeks and complete degradation of the sponges by 16
      weeks, with only a minimal inflammatory response being observed over the course
      of the experiments.

PMID- 24561712
TI  - Chondroitin-6-sulfate attenuates inflammatory responses in murine macrophages via
      suppression of NF-kappaB nuclear translocation.
AB  - Inflammation is a host protective response to noxious stimuli, and excessive
      production of pro-inflammatory mediators by macrophages (mphi) can lead to
      numerous pathological conditions. In this study, immunomodulatory effects of
      immobilized and soluble glycosaminoglycans (GAGs) on mouse-bone-marrow-derived
      mphi were compared by measuring nitric oxide (NO). We demonstrate here that all
      GAGs studied except for heparin were able to modulate interferon
      gamma/lipopolysaccharide (IFN-gamma/LPS)-induced NO release by mphi to varying
      extents after 24h of incubation. In particular, the modulatory activities of
      soluble chondroitin-6-sulfate (C6S), hyaluronic acid and heparan sulfate altered
      markedly after covalent immobilization. Of these, soluble C6S exhibited the
      strongest NO inhibitory activity, and the inhibition was dose- and time
      dependent. Moreover, C6S significantly reduced pro-inflammatory cytokines
      interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha production by IFN
      gamma/LPS- or LPS-activated mphi. Specifically, the C6S-mediated suppression of
      mphi pro-inflammatory phenotype was accompanied by an increase in the IL-10
      level, suggesting a possible switch towards anti-inflammatory/wound healing M2
      state. In addition, the highest magnitude of inhibitory effects was obtained when
      cells were pre-treated with C6S prior to IFN-gamma/LPS or LPS challenge,
      suggesting an additional role for C6S in protection against microbial infection.
      Further investigations reveal that the anti-inflammatory effects of C6S on
      activated mphi may be ascribed at least in part to suppression of NF-kappaB
      nuclear translocation.

PMID- 24561713
TI  - Cellular uptake of multilayered capsules produced with natural and genetically
      engineered biomimetic macromolecules.
AB  - Multilayered microcapsules of chitosan and biomimetic elastin-like recombinamers
      (ELRs) were prepared envisaging the intracellular delivery of active agents. Two
      ELRs containing either a bioactive RGD sequence or a scrambled non-functional RDG
      were used to construct two types of functionalized polymeric microcapsules, both
      of spherical shape ~4MUm in diameter. Cell viability studies with human
      mesenchymal stem cells (hMSCs) were performed using microcapsule/cell ratios
      between 5:1 and 100:1. After 3 and 72h of co-incubation, no signs of cytotoxicity
      were found, but cells incubated with RGD-functionalized microcapsules exhibited
      higher viability values than RDG cells. The internalization efficacy and
      bioavailability of encapsulated DQ-ovalbumin were assessed by monitoring the
      fluorescence changes in the cargo. The data show that surface functionalization
      did not significantly influence internalization by hMSCs, but the bioavailability
      of DQ-ovalbumin degraded faster when encapsulated within RGD-functionalized
      microcapsules. The microcapsules developed show promise for intracellular drug
      delivery with increased drug efficacy.

PMID- 24561714
TI  - Grape marc extract causes early perception events, defence reactions and
      hypersensitive response in cultured tobacco cells.
AB  - Grape marc extract (GME) showed elicitor activity on suspension-cultured cells of
      tobacco. The BY-2 cells reacted to GME (0.25% and 0.125%) with a long-sustained
      pH rise in their growth medium. Using EGTA or LaCl3, we showed that extracellular
      alkalinization depended on Ca(2+) mobilization. The tobacco BY-2 cells challenged
      with GME promoted cell death and the upregulation of defence-related genes such
      as PR3, PAL and CCoAOMT. Cell death rate was quantified using an experimental
      calibrated Evans Blue assay. The GME-induced cell death was dose-dependent and
      occurred in 24 h. Longer exposure increased the extent of tobacco cell death. To
      investigate a potential hypersensitive reaction, we tested the effect of various
      inhibitors of protein synthesis (cycloheximide) and proteases (aprotinin,
      pepstatin and E-64) on GME-induced cell death. All these chemicals reduced GME
      induced cell death rate in 30 min. Overall, our findings indicate that GME
      elicits early perception events, defence reactions and cell death requiring
      protein synthesis and proteases. 

PMID- 24561715
TI  - Effects of the sequence characteristics of miRNAs on multi-viral resistance
      mediated by single amiRNAs in transgenic tobacco.
AB  - Artificial microRNA (amiRNA) has become the preferred viral defence that can be
      induced in plants. In this study, nine amiRNA target sites were selected that
      were based on the sequence characteristics of natural miRNAs in the cylindrical
      inclusion protein (CI), nuclear inclusion a protein (NIa), nuclear inclusion b
      protein (NIb), and coat protein (CP) genes of Potato virus Y (PVY(N)). These
      amiRNAs that exhibited high similarities to the sequences of PVY(N) and TEV-SD1
      were considered. To study the effectiveness of gene silencing in amiRNA-mediated
      viral resistance, we constructed nine amiRNA plant expression vectors by
      replacing the functional sequences of miRNA319a precursors with our selected
      amiRNA sequences. These constructs were subsequently introduced to tobacco
      plants. A Northern blot assay verified that the nine amiRNA plant expression
      vectors could successfully express amiRNAs in plants. The analysis of viral
      resistance demonstrated that these transgenic tobacco plants could effectively
      inhibit PVY(N) and TEV-SD1 viral infections. The amiRNA that targeted the NIb and
      CP genes displayed a higher silencing efficiency than did the amiRNAs targeted CI
      and NIa genes. Northern blot analysis demonstrated that silencing was induced by
      the original amiRNAs and could be bilaterally extended by the siRNA pathway. That
      is, the amiRNA and the secondary siRNA mediated the degradation of viral RNA
      together. Genetic analysis demonstrated that the trait for viral resistance in
      transgenic plants can be consistently inherited via a single copy of the
      transgenic sequence. Considering the correlation between the sequence
      characteristics and the activity of amiRNA, we concluded that a few mismatched
      bases between the amiRNA and the target sequence could be allowed, particularly
      the mismatched bases in the 3' end of the amiRNA. 

PMID- 24561716
TI  - Identification of a new series of amides as non-covalent proteasome inhibitors.
AB  - Proteasome inhibition has emerged as an important therapeutic strategy for the
      treatment of multiple myeloma (MM) and some forms of lymphoma, with potential
      application in other types of cancers. 20S proteasome consists of three different
      catalytic activities known as chymotrypsin-like (ChT-L), trypsin-like (T-L), and,
      post-glutamyl peptide hydrolyzing (PGPH) or caspase-like (C-L), which are located
      respectively on the beta5, beta2, and beta1 subunits of each heptameric beta
      rings. Currently a wide number of covalent proteasome inhibitors are reported in
      literature; however, the less widely investigated non-covalent inhibitors might
      be a promising alternative to employ in therapy, because of the lack of all
      drawbacks and side-effects related to irreversible inhibition. In the present
      work we identified a series of amides, two of which (1b and 1f) are good
      candidates to non-covalent inhibition of the chymotrypsin-like activity of the
      beta5 proteasome subunit. The non-covalent binding mode was corroborated by
      docking simulations of the most active inhibitors 1b, 1f and 2h into the yeast
      20S proteasome crystal structure. 

PMID- 24561717
TI  - A standardized obstacle course for assessment of visual function in ultra low
      vision and artificial vision.
AB  - We describe an indoor, portable, standardized course that can be used to evaluate
      obstacle avoidance in persons who have ultralow vision. Six sighted controls and
      36 completely blind but otherwise healthy adult male (n=29) and female (n=13)
      subjects (age range 19-85 years), were enrolled in one of three studies involving
      testing of the BrainPort sensory substitution device. Subjects were asked to
      navigate the course prior to, and after, BrainPort training. They completed a
      total of 837 course runs in two different locations. Means and standard
      deviations were calculated across control types, courses, lights, and visits. We
      used a linear mixed effects model to compare different categories in the PPWS
      (percent preferred walking speed) and error percent data to show that the course
      iterations were properly designed. The course is relatively inexpensive, simple
      to administer, and has been shown to be a feasible way to test mobility function.
      Data analysis demonstrates that for the outcome of percent error as well as for
      percentage preferred walking speed, that each of the three courses is different,
      and that within each level, each of the three iterations are equal. This allows
      for randomization of the courses during administration.

PMID- 24561718
TI  - The origin of segmentation motor activity in the intestine.
AB  - The segmentation motor activity of the gut that facilitates absorption of
      nutrients was first described in the late 19th century, but the fundamental
      mechanisms underlying it remain poorly understood. The dominant theory suggests
      alternate excitation and inhibition from the enteric nervous system. Here we
      demonstrate that typical segmentation can occur after total nerve blockade. The
      segmentation motor pattern emerges when the amplitude of the dominant pacemaker,
      the slow wave generated by interstitial cells of Cajal associated with the
      myenteric plexus (ICC-MP), is modulated by the phase of induced lower frequency
      rhythmic transient depolarizations, generated by ICC associated with the deep
      muscular plexus (ICC-DMP), resulting in a waxing and waning of the amplitude of
      the slow wave and a rhythmic checkered pattern of segmentation motor activity.
      Phase-amplitude modulation of the slow waves points to an underlying system of
      coupled nonlinear oscillators originating in the networks of ICC. 

PMID- 24561719
TI  - Preparation of primary neurons for visualizing neurites in a frozen-hydrated
      state using cryo-electron tomography.
AB  - Neurites, both dendrites and axons, are neuronal cellular processes that enable
      the conduction of electrical impulses between neurons. Defining the structure of
      neurites is critical to understanding how these processes move materials and
      signals that support synaptic communication. Electron microscopy (EM) has been
      traditionally used to assess the ultrastructural features within neurites;
      however, the exposure to organic solvent during dehydration and resin embedding
      can distort structures. An important unmet goal is the formulation of procedures
      that allow for structural evaluations not impacted by such artifacts. Here, we
      have established a detailed and reproducible protocol for growing and flash
      freezing whole neurites of different primary neurons on electron microscopy grids
      followed by their examination with cryo-electron tomography (cryo-ET). This
      technique allows for 3-D visualization of frozen, hydrated neurites at nanometer
      resolution, facilitating assessment of their morphological differences. Our
      protocol yields an unprecedented view of dorsal root ganglion (DRG) neurites, and
      a visualization of hippocampal neurites in their near-native state. As such,
      these methods create a foundation for future studies on neurites of both normal
      neurons and those impacted by neurological disorders. 

PMID- 24561720
TI  - Naringenin exerts cytoprotective effect against paraquat-induced toxicity in
      human bronchial epithelial BEAS-2B cells through NRF2 activation.
AB  - We have previously shown that paraquat (PQ)-induced oxidative stress causes
      dramatic damage in various human cell lines. Naringenin (NG) is an active
      flavanone, which has been reported to have beneficial bioactivities, including
      antioxidative, anti-inflammatory, and antitumorigenic activities, with a
      relatively low toxicity to normal cells. In this study, we intended to assess the
      cytoprotective effect of NG against PQ-induced toxicity in the human bronchial
      epithelial BEAS-2B cell line. Co-treatment with NG in PQ-treated BEAS-2B cells
      can reduce PQ-induced cellular toxicity. NG can also decrease the generation of
      intracellular ROS caused by PQ treatment. We also observed that treatment with NG
      in PQ-exposed BEAS-2B cells can significantly induce the expression of
      antioxidant-related genes, including GPX2, GPX3, GPX5, and GPX7. NG co-treatment
      can also activate the NRF2 transcription factor and promote its nuclear
      translocation. In addition, NG co-treatment can induce the expression of NRF2
      downstream target genes such as that of heme oxygenase-1 (HO-1) and NAD(P)H:
      quinone oxidoreductase 1 (NQO1). A small interfering RNA study revealed that the
      knockdown of NRF2 can abrogate NG-mediated protection of the cells from PQ
      induced cellular toxicity. We propose that NG effectively alleviates PQ-induced
      cytotoxicity in human bronchial epithelial BEAS-2B cells through the NRF2
      regulated antioxidant defense pathway, and NG might be a good therapeutic
      candidate molecule in oxidative stress-related diseases.

PMID- 24561721
TI  - Butyric acid fermentation of sodium hydroxide pretreated rice straw with
      undefined mixed culture.
AB  - This study describes an alternative mixed culture fermentation technology to
      anaerobically convert lignocellulosic biomass into butyric acid, a valuable
      product with wide application, without supplementary cellulolytic enzymes. Rice
      straw was soaked in 1% NaOH solution to increase digestibility. Among the tested
      pretreatment conditions, soaking rice straw at 50 degrees C for 72 h removed ~66%
      of the lignin, but retained ~84% of the cellulose and ~71% of the hemicellulose.
      By using an undefined cellulose-degrading butyrate-producing microbial community
      as butyric acid producer in batch fermentation, about 6 g/l of butyric acid was
      produced from the pretreated rice straw, which accounted for ~76% of the total
      volatile fatty acids. In the repeated-batch operation, the butyric acid
      production declined batch by batch, which was most possibly caused by the shift
      of microbial community structure monitored by denaturing gradient gel
      electrophoresis. In this study, batch operation was observed to be more suitable
      for butyric acid production. 

PMID- 24561722
TI  - Cell-recycle continuous fermentation of Enterococcus faecalis RKY1 for economical
      production of lactic acid by reduction of yeast extract supplementation.
AB  - Both lactic acid productivity and cell growth were linearly correlated with yeast
      extract supplementation in batch fermentation. During conventional continuous
      operation, although fresh feed was introduced into the bioreactor with a
      significantly low dilution rate (0.04 h(-1)), the amount of yeast extract
      employed was not enough to maintain the growth of microorganism. However, when
      the fresh feed contained 100 g/l glucose and 2 g/l yeast extract during cell
      recycle continuous operation at a dilution rate of 0.04 h(-1), more than 90 g/l
      lactic acid was continuously produced, with the average productivity of 3.72
      g/l.h. In this experiment, 82 g of yeast extract (77% of reduction yield) could
      be reduced for the production of 1 kg of lactic acid compared with batch
      fermentation of a similar volumetric productivity.

PMID- 24561723
TI  - Construction of artificial biosynthetic pathways for resveratrol glucoside
      derivatives.
AB  - Resveratrol, which is a polyphenolic antioxidant, is dose-dependent when used to
      provide health benefits, to enhance stress resistance, and to extend lifespans.
      However, even though resveratrol has therapeutic benefits, its clinical
      therapeutic effect is limited owing to its low oral bioavailability. An
      Escherichia coli system was developed that contains an artificial biosynthetic
      pathway that produces resveratrol glucoside derivatives, such as resveratrol-3
      Oglucoside (piceid) and resveratrol-4'-O-glucoside (resveratroloside), from
      simple carbon sources. This artificial biosynthetic pathway contains a
      glycosyltransferase addition (YjiC from Bacillus) with resveratrol biosynthetic
      genes. The produced glucoside compounds were verified through the presence of a
      product peak(s) and also through LC/MS analyses. The strategy used in this
      research demonstrates the first harnessing of E. coli for de novo synthesis of
      resveratrol glucoside derivatives from a simple sugar medium.

PMID- 24561724
TI  - The influence of particle size on radionuclide activity concentrations in Tejo
      River sediments.
AB  - Sediment samples from Tejo River were analyzed for (228)Ra, (226)Ra, (137)Cs and
      (40)K by HPGe gamma spectrometry. The activity concentration data were
      statistically analyzed. The activity concentrations values were in the range of
      about two orders of magnitude for each radionuclide. The influence of the
      particle size on the radionuclide concentrations was observed. The different
      environmental origins of the radionuclides (228)Ra, (226)Ra, (137)Cs and (40)K,
      in the sediments were demonstrated through correlation analysis. Cluster analysis
      showed a close relationship between (228)Ra and (226)Ra and a different behavior
      for (40)K. The data obtained in this study provides useful information on the
      background radioactivity of the studied area and can be further used for
      radiological mapping of the Tejo River. 

PMID- 24561725
TI  - Bending springback behavior related to deformation-induced phase transformations
      in Ti-12Cr and Ti-29Nb-13Ta-4.6Zr alloys for spinal fixation applications.
AB  - The springback behavior of Ti-12Cr and Ti-29Nb-13Ta-4.6Zr (TNTZ) during
      deformation by bending was investigated; and the microstructures of the non
      deformed and deformed parts of both alloys were systematically examined to
      clarify the relationship between microstructure and springback behavior. For the
      deformed Ti-12Cr alloy, deformation-induced omega-phase transformation occurs in
      both the areas of compression and tension within the deformed part, which
      increases the Young's modulus. With the deformed TNTZ alloy, deformation-induced
      omega-phase transformation is observed in the area of compression within the
      deformed part; while a deformation-induced alpha" martensite transformation
      occurs in the area under tension, which is likely to be associated with the
      pseudoelasticity of TNTZ. Among these two alloys, Ti-12Cr exhibits a smaller
      springback and a much greater bending strength when compared with TNTZ; making Ti
      12Cr the more advantageous for spinal fixation applications. 

PMID- 24561726
TI  - The predicted secretomes of Monosiga brevicollis and Capsaspora owczarzaki, close
      unicellular relatives of metazoans, reveal new insights into the evolution of the
      metazoan extracellular matrix.
AB  - The extracellular matrix (ECM) is a major mediator of multi-cellularity in the
      metazoa. Multiple ECM proteins are conserved from sponges to human, raising
      questions about the evolutionary origin of ECM. Choanoflagellates are the closest
      unicellular relatives of the metazoa and proteins with domains characteristic of
      metazoan ECM proteins have been identified from the genome-predicted proteome of
      the choanoflagellate Monosiga brevicollis. However, a systematic analysis of M.
      brevicollis secretory signal peptide-containing proteins with ECM domains has
      been lacking. We analysed all predicted secretory signal-peptide-containing
      proteins of M. brevicollis for ECM domains. Nine domains that are widespread in
      metazoan ECM proteins are represented, with EGF, fibronectin III, laminin G, and
      von Willebrand Factor_A domains being the most numerous. Three proteins contain
      more than one category of ECM domain, however, no proteins correspond to the
      domain architecture of metazoan ECM proteins. The fibronectin III domains are all
      present within glycoside hydrolases and none contain an integrin-binding motif.
      Glycosaminoglycan-binding motifs identified in animal thrombospondin type 1
      domains are conserved in some M. brevicollis representatives of this domain,
      whereas there is little evidence of conservation of glycosaminoglycan-binding
      motifs in the laminin G domains. The identified proteins were compared with the
      predicted secretory ECM domain-containing proteins of the integrin-expressing
      filasterean, Capsaspora owczarzaki. C. owczarzaki encodes a smaller number of
      secretory, ECM domain-containing proteins and only EGF, fibronectin type III and
      laminin G domains are represented. The M. brevicollis and C. owczarzaki proteins
      have distinct domain architectures and all proteins differ in their domain
      architecture to metazoan ECM proteins. These identifications provide a basis for
      future experiments to validate the extracellular location of these proteins and
      uncover their functions in choanoflagellates and C. owczarzaki. The data
      strengthen the model that ECM proteins are metazoan-specific and evolved as
      innovations in the last common metazoan ancestor. 

PMID- 24561727
TI  - Multiple pi-bands and Bernal stacking of multilayer graphene on C-face SiC,
      revealed by nano-Angle Resolved Photoemission.
AB  - Only a single linearly dispersing pi-band cone, characteristic of monolayer
      graphene, has so far been observed in Angle Resolved Photoemission (ARPES)
      experiments on multilayer graphene grown on C-face SiC. A rotational disorder
      that effectively decouples adjacent layers has been suggested to explain this.
      However, the coexistence of MUm-sized grains of single and multilayer graphene
      with different azimuthal orientations and no rotational disorder within the
      grains was recently revealed for C-face graphene, but conventional ARPES still
      resolved only a single pi-band. Here we report detailed nano-ARPES band mappings
      of individual graphene grains that unambiguously show that multilayer C-face
      graphene exhibits multiple pi-bands. The band dispersions obtained close to the K
      point moreover clearly indicate, when compared to theoretical band dispersion
      calculated in the framework of the density functional method, Bernal (AB)
      stacking within the grains. Thus, contrary to earlier claims, our findings imply
      a similar interaction between graphene layers on C-face and Si-face SiC.

PMID- 24561728
TI  - Surgical or transcatheter mitral valve intervention: complex disease requires
      complex decisions.

PMID- 24561729
TI  - Cardiac conduction disturbances after transcatheter aortic valve replacement:
      much remains to be learned.

PMID- 24561730
TI  - Chronic total coronary occlusion percutaneous intervention.

PMID- 24561731
TI  - Reduction of pacemaker implantation rates after CoreValve(r) implantation by
      moderate predilatation.
AB  - AIMS: We investigated the impact of the diameter of the valvuloplasty balloon
      (VB) used for predilation before transcatheter aortic valve implantation (TAVI)
      on atrioventricular block formation with consecutive need for permanent pacemaker
      (PP) implantation. METHODS AND RESULTS: TAVI was performed in 269 consecutive
      patients using the CoreValve prosthesis (Medtronic) via transfemoral access under
      local anaesthesia with mild analgesic medication. After exclusion of 32 patients
      with previously implanted PP, 237 patients were included in a retrospective
      analysis of the impact of VB size on subsequent PP incidence. Implantation
      success rate was 99.3%. Periprocedural mortality was 0%, and 30-day mortality was
      5.9%. PP implantation after TAVI was required by 21.1%. Of 114 patients treated
      by 25 mm balloon valvuloplasty, a PP was implanted in 27.1%. In 123 patients, who
      were treated by VB with a <=23 mm diameter, the PP implantation rate decreased to
      15.4% (p=0.04). In univariate analysis, larger VB size resulted in a greater
      prevalence of PP implantation after TAVI. After adjustment by multivariate
      analysis for baseline clinical and operative characteristics, VB size remained an
      independent predictor of PP implantation. CONCLUSIONS: Moderate balloon
      predilation in patients undergoing TAVI with the Medtronic CoreValve prosthesis
      reduces the PP rate without affecting procedural success.

PMID- 24561732
TI  - Transcatheter treatment for refractory angina with the Coronary Sinus Reducer.
AB  - AIMS: To evaluate the clinical efficacy of the coronary sinus (CS) Reducer in
      attenuating angina severity in patients suffering from severe refractory angina.
      METHODS AND RESULTS: Patients with refractory angina, objective evidence of
      myocardial ischaemia and no option for revascularisation were treated with CS
      Reducer implantation at two medical centres. Six-month follow-up evaluation
      consisted of clinical assessment of angina severity. Objective assessment of
      ischaemia at six-month follow-up was performed in one of the two centres.
      Successful CS Reducer implantation was achieved in 21 of 23 eligible patients, at
      both centres. No device-related adverse effects were observed during the
      procedure or the follow-up period. Canadian Cardiovascular Society (CCS) score
      diminished from a mean of 3.3 at baseline to 2.0 at six months (n=20, p<0.01),
      exercise duration was prolonged from 3:16 to 5:16 min (min:sec; n=8, p=0.05).
      Thallium SPECT summed stress score and summed difference score were both reduced
      (n=9, 21.5+/-10 vs.13.2+/-9, p=0.01, and 11.1+/-6 vs. 4.7+/-4, p=0.007,
      respectively). Wall motion score index at peak dobutamine infusion was also
      significantly improved (n=8, 1.9+/-0.4 vs. 1.4+/-0.4, p=0.046). CONCLUSIONS: CS
      Reducer implantation was safe and resulted in significant improvement of angina
      class. The results of the ongoing randomised sham-control trial will address the
      concern regarding the possible placebo effect, and hopefully further support our
      encouraging observations.

PMID- 24561733
TI  - Relationship between initial treatment strategy and quality of life in patients
      with coronary chronic total occlusions.
AB  - AIMS: Our objective was to evaluate the relationship between coronary chronic
      total occlusion (CTO) treatment strategy and quality of life improvements.
      METHODS AND RESULTS: This multicentre prospective cohort study enrolled
      consecutive CTO patients undergoing a non-urgent coronary angiogram who completed
      the Seattle Angina Questionnaire (SAQ) and EQ-5D at baseline and at one year.
      Strategies were: i) medical therapy, ii) PCI to non-CTO, iii) PCI to CTO, and iv)
      CABG. Multivariable regression models compared quality of life changes over time
      among strategies, accounting for repeat measures per patient. In our cohort of
      387 patients, 154 underwent medical therapy, 83 had PCI to the non-CTO artery,
      104 underwent CABG, and 46 underwent PCI to the CTO. Medically treated patients
      had no improvement on any SAQ domains. Patients with revascularisation of the CTO
      territory with either PCI or CABG had significant improvements in the physical
      limitation (PCI to CTO 60.5-76.4; CABG 61.6-80.1; p<0.001), angina frequency (PCI
      to CTO 79.0-92.7; CABG 82.1-97.9; p<0.001), and disease perception (PCI to CTO
      50.5-75.0; CABG 50.2-80.0; p<0.001) domains. In non-CTO PCI patients, improvement
      was restricted to the angina frequency (82.8-93.3; p<0.001), and disease
      perception (53.8-71.4; p<0.001) domains. CONCLUSIONS: CTO territory
      revascularisation was associated with quality of life improvements.

PMID- 24561734
TI  - Predictors of contrast-induced nephropathy in chronic total occlusion
      percutaneous coronary intervention.
AB  - AIMS: Contrast-induced nephropathy (CIN) is a leading cause of morbidity and
      mortality in patients undergoing percutaneous coronary intervention (PCI).
      Limited data, however, are available on predictors of CIN in PCI for chronic
      total occlusion (CTO) lesions. The aim of the study was to determine the risk of
      developing CIN in patients undergoing CTO PCI by studying the effects of clinical
      variables, interventional techniques, and CTO lesion characteristics on renal
      function. METHODS AND RESULTS: This retrospective analysis included consecutive
      patients referred for CTO PCI between January 2002 and December 2009. CIN was
      defined as an elevated serum creatinine level >=25% of baseline serum creatinine
      level at 48-72 hours after procedure. Patient characteristics, Mehran score,
      lesion characteristics, interventional procedure, and devices used were compared
      between CIN and non-CIN groups. For the 516 patients eligible for analysis, the
      incidence of CIN was 5.4% (28/516). Two patients needed transient haemodialysis
      (0.4%, 2/516). Analysis of risk using Mehran scoring found that the incidence of
      CIN was 0.5% (1/207) among low-risk patients, 3.4% (7/205) among moderate-risk
      patients, 15.9% (14/88) among high-risk patients and 37.5% (6/16) among very high
      risk patients. The Mehran score high-risk group (11-15) and the very high-risk
      group (>=16) were definitely predictors of CIN after CTO PCI (OR: 27.022 [95% CI:
      2.787-262.028, p=0.004]; OR: 32.512 [95% CI: 2.149-491.978, p=0.012]). Severe
      tortuosity was the only predictor of CIN after CTO PCI in angiographic and
      procedural findings (OR: 6.621 [95% CI: 1.090-40.227, p=0.040]). CONCLUSIONS:
      Being in the Mehran score high-risk group (11-15) or the very high-risk group
      (>=16) and severe tortuosity were predictors of CIN after CTO PCI.

PMID- 24561735
TI  - Lumen enlargement of the coronary segments located distal to chronic total
      occlusions successfully treated with drug-eluting stents at follow-up.
AB  - AIMS: Chronic total occlusions (CTO) are the final stage of atherosclerosis.
      Occluded coronary arteries have large plaque burden and negative remodelling. The
      aim of this study was to assess lumen and vessel changes of segments located
      distal to successfully recanalised CTO. METHODS AND RESULTS: Ninety-one CTO
      treated with drug-eluting stents underwent quantitative coronary angiography
      (QCA) at baseline and at 12-18 months; 31 underwent serial intravascular
      ultrasound (IVUS) imaging. Angiographic changes were assessed with QCA as
      differences in minimal, mean and maximal lumen diameter (MinLD, MeanLD and MaxLD,
      respectively). Vessel changes were assessed with IVUS as changes in plaque and
      vessel volume. At follow-up, angiographic MinLD increased 23.9% (from 0.88+/-0.32
      to 1.09+/-0.35 mm; p<0.01), MeanLD 16.4% (from 1.59+/-0.44 to 1.85+/-0.45 mm;
      p<0.01) and MaxLD 11.7% (from 2.39+/-0.67 to 2.67+/-0.70 mm; p<0.01). Lumen
      enlargement was greater in non-restenotic lesions, small lumen area at the end of
      the index procedure and low LDL-cholesterol levels during the study. By IVUS,
      lumen volume increased 26.9% (from 108.1+/-89.2 to 137.3+/-115.3 mm3; p<0.01),
      vessel volume increased 12.1% (from 207.1+/-170.2 to 232.2+/-196.0 mm3; p<0.01)
      and plaque volume tended to decrease 3.9% (from 98.9+/-88.7 to 94.9+/-89.3 mm3;
      p=0.07). Small lumen at baseline was related to greater lumen enlargement.
      CONCLUSIONS: Segments distal to recanalised CTO showed a notable lumen and vessel
      enlargement with a trend toward mild plaque regression. Low LDL-cholesterol
      levels increase lumen enlargement.

PMID- 24561736
TI  - Patients undergoing PCI from the femoral route by default radial operators are at
      high risk of vascular access-site complications.
AB  - AIMS: Radial artery (RA) access for PCI has a lower incidence of vascular access
      site (VAS) complications than the femoral artery (FA) approach. However, even for
      default radial operators certain patients are intervened upon from the FA. We
      examined the demographics and incidence of VAS complications when default radial
      operators resort to the FA for PCI. METHODS AND RESULTS: The demographics and VAS
      complications were compared by access site retrospectively for all PCI cases
      performed by default radial operators (n=1,392). A modified ACUITY trial
      definition of major VAS complication was used. FA puncture occurred in 25.2%
      (351/1,392) of cases. Patients were more likely to be female, older and weigh
      less than patients undergoing PCI from the RA. The FA procedure was likely to be
      more complex with larger sheaths, more left main stem, graft and multivessel
      intervention, and there was a greater proportion of emergency cases. Despite
      increased case complexity, glycoprotein inhibitors were used less frequently in
      femoral cases (26.5% vs. 36.8%, p<0.001). A VAS complication occurred in 12.5%
      (44/351) of cases. CONCLUSIONS: The risk factors for access-site bleeding are
      disproportionately high in the population requiring FA puncture by default radial
      operators, and as a result such patients have a high rate of vascular access-site
      complications.

PMID- 24561737
TI  - Evaluation of coronary microvascular function by left ventricular contractile
      reserve with low-dose dobutamine echocardiography.
AB  - AIMS: Coronary microvascular function has important diagnostic and prognostic
      implications but routine assessment is difficult. The index of microcirculatory
      resistance (IMR) is a reliable but invasive measure. We evaluated whether left
      ventricular contractile reserve (CR), measured with strain imaging on dobutamine
      echocardiography (DSE), is a reliable non-invasive measure of coronary
      microvascular function. METHODS AND RESULTS: Forty-five patients underwent low
      dose DSE and invasive coronary angiography with IMR measurement in the left
      anterior descending artery. Global mean peak systolic longitudinal strain was
      measured in three apical views at rest, and with low-dose DSE. CR was the
      difference between the resting and low-dose values. Mean IMR was 19.8 (range 6
      104): mean peak global systolic strain at rest was -17.90% and at low-dose was 
      21.46%, giving a mean CR of +3.6% (20% relative increase). IMR and CR were
      significantly correlated, IMR(-1)=(0.0014*CR+0.05), r=0.64, p<0.001. CR of >=10%
      relative increase identified IMR <25 (100% sensitivity and specificity) and <16
      (93% sensitivity, 50% specificity [AUC=0.84]). CR >=20% identified IMR of <16
      (78% sensitivity, 82% specificity) with CR >= 41% having 100% specificity.
      CONCLUSIONS: LV CR with low-dose DSE may be used to estimate IMR non-invasively.
      An impaired CR indicates coronary microvascular dysfunction.

PMID- 24561738
TI  - First-in-man experience with cryoplasty during graded balloon atrial septostomy
      to reduce spontaneous closure in a patient with severe pulmonary arterial
      hypertension.

PMID- 24561739
TI  - Folded Melody valve technique for complex right ventricular outflow tract.
AB  - Percutaneous implantation with the Melody((r)) valve (Medtronic Inc.,
      Minneapolis, MN, USA) has achieved standard of care for the management of
      patients with dysfunctional right ventricle (RV) to pulmonary artery (PA)
      conduits. The right ventricular outflow tract (RVOT) landing zone dimensions may
      vary significantly making it unfavourable for Melody valve implantation. We
      report a novel technique of "folded Melody valve" in a patient with complex,
      dysfunctional RV to the PA conduit.

PMID- 24561740
TI  - Tools and techniques - statistics: comments on a cost-effectiveness study of TAVI
      for patients with inoperable aortic stenosis.

PMID- 24561741
TI  - How should I treat an asymptomatic enlarging giant saphenous vein graft aneurysm?

PMID- 24561742
TI  - Challenges and responses in human vaccine development.
AB  - Human vaccine development remains challenging because of the highly sophisticated
      evasion mechanisms of pathogens for which vaccines are not yet available. Recent
      years have witnessed both successes and failures of novel vaccine design and the
      strength of iterative approaches is increasingly appreciated. These combine
      discovery of novel antigens, adjuvants and vectors in the preclinical stage with
      computational analyses of clinical data to accelerate vaccine design. Reverse and
      structural vaccinology have revealed novel antigen candidates and molecular
      immunology has led to the formulation of promising adjuvants. Gene expression
      profiles and immune parameters in patients, vaccinees and healthy controls have
      formed the basis for biosignatures that will provide guidelines for future
      vaccine design. 

PMID- 24561743
TI  - The relevance of analogue studies for understanding obsessions and compulsions.
AB  - Analogue samples are often used to study obsessive-compulsive (OC) symptoms and
      related phenomena. This approach is based on the hypothesis that results derived
      from such samples are relevant to understanding OC symptoms in individuals with a
      diagnosis of obsessive-compulsive disorder (OCD). Two decades ago, Gibbs (1996)
      reviewed the available literature and found initial support for this hypothesis.
      Since then there have been many important advances addressing this issue. The
      purpose of the present review was to synthesize various lines of research
      examining the assumptions of using analogue samples to draw inferences about
      people with OCD. We reviewed research on the prevalence of OC symptoms in non
      clinical populations, the dimensional (vs. categorical) nature of these symptoms,
      phenomenology, etiology, and studies on developmental and maintenance factors in
      clinical and analogue samples. We also considered the relevance of analogue
      samples in OCD treatment research. The available evidence suggests research with
      analogue samples is highly relevant for understanding OC symptoms. Guidelines for
      the appropriate use of analogue designs and samples are suggested. 

PMID- 24561744
TI  - Inhibition of miR-146a prevents enterovirus-induced death by restoring the
      production of type I interferon.
AB  - There are no antivirals or vaccines available to treat Enterovirus 71 (EV71)
      infections. Although the type I interferon response, elicited upon virus
      infection, is critical to establishing host antiviral innate immunity, EV71 fails
      to induce this response efficiently. Here we provide new insights into potential
      anti-EV71 therapy by showing that neutralization of EV71-induced miR-146a
      prevents death in mice by restarting the production of type I interferon. EV71
      infection upregulates miR-146a, which targets IRAK1 and TRAF6 involved in TLR
      signalling and type I interferon production. We further identify AP1 as being
      responsible for the EV71-induced expression of miR-146a. Surprisingly, knocking
      out miR-146a or neutralizing virus-induced miR-146a by specific antagomiR
      restores expressions of IRAK1 and TRAF6, augments IFNbeta production, inhibits
      viral propagation and improves survival in the mouse model. Our results suggest
      that enterovirus-induced miR-146a facilitates viral pathogenesis by suppressing
      IFN production and provide a clue to developing preventive and therapeutic
      strategies for enterovirus infections. 

PMID- 24561747
TI  - The Strategic Framework on Multiple Chronic Conditions.

PMID- 24561745
TI  - Pulse wave velocity testing in the Baltimore longitudinal study of aging.
AB  - Carotid-femoral pulse wave velocity is considered the gold standard for
      measurements of central arterial stiffness obtained through noninvasive
      methods(1). Subjects are placed in the supine position and allowed to rest
      quietly for at least 10 min prior to the start of the exam. The proper cuff size
      is selected and a blood pressure is obtained using an oscillometric device. Once
      a resting blood pressure has been obtained, pressure waveforms are acquired from
      the right femoral and right common carotid arteries. The system then
      automatically calculates the pulse transit time between these two sites (using
      the carotid artery as a surrogate for the descending aorta). Body surface
      measurements are used to determine the distance traveled by the pulse wave
      between the two sampling sites. This distance is then divided by the pulse
      transit time resulting in the pulse wave velocity. The measurements are performed
      in triplicate and the average is used for analysis.

PMID- 24561748
TI  - Heterogeneity in the quality of care for patients with multiple chronic
      conditions by psychiatric comorbidity.
AB  - BACKGROUND: Little is known about the quality of care received by Medicaid
      enrollees with multiple chronic conditions (MCCs) and whether quality is
      different for those with mental illness. OBJECTIVES: To examine cancer screening
      and single-disease quality of care measures in a Medicaid population with MCC and
      to compare quality measures among persons with MCC with varying medical
      comorbidities with and without depression or schizophrenia. RESEARCH DESIGN:
      Secondary data analysis using a unique data source combining Medicaid claims with
      other administrative datasets from North Carolina's mental health system.
      SUBJECTS: Medicaid-enrolled adults aged 18 and older with >=2 of 8 chronic
      conditions (asthma, chronic obstructive pulmonary disease, diabetes,
      hypertension, hyperlipidemia, seizure disorder, depression, or schizophrenia).
      Medicare/Medicaid dual enrollees were excluded due to incomplete data on their
      medical care utilization. MEASURES: We examined a number of quality measures,
      including cancer screening, disease-specific metrics, such as receipt of
      hemoglobin A1C tests for persons with diabetes, and receipt of psychosocial
      therapies for persons with depression or schizophrenia, and medication adherence.
      RESULTS: Quality of care metrics was generally lower among those with depression
      or schizophrenia, and often higher among those with increasing levels of medical
      comorbidities. A number of exceptions to these trends were noted. CONCLUSIONS:
      Cancer screening and single-disease quality measures may provide a benchmark for
      overall quality of care for persons with MCC; these measures were generally lower
      among persons with MCC and mental illness. Further research on quality measures
      that better reflect the complex care received by persons with MCC is essential.

PMID- 24561749
TI  - Patients' body mass index and blood pressure over time: diagnoses, treatments,
      and the effects of comorbidities.
AB  - BACKGROUND: A national strategic framework to address multiple chronic conditions
      has called for further research on disease trajectories of patients with
      comorbidities. METHODS: An observational study using multilevel models to analyze
      electronic health record data from a multispecialty practice from 2003 to 2010 to
      examine disease trajectories of patients with at least 2 of 3 common chronic
      conditions: overweight/obese, hypertension, and depression. Using longitudinal
      data on up to 110,000 patients, the effects of comorbidities on the probability
      of having a diagnosis for overweight/obesity or hypertension and on the
      trajectories of body mass index (BMI) and blood pressure (BP) over time were
      examined. RESULTS: From 2003 to 2010, the percentage of patients with high BMI
      receiving an overweight/obesity diagnosis grew from 5.0% to 18.7%, and the
      percentage of patients with high BP having a hypertension diagnosis rose from
      39.9% to 51.7%. The effect of time for patients with high BMI and depression was
      less than the effect of time for high BMI only patients (P<0.01) in receiving
      overweight/obesity diagnoses. Co-occurring depression and high BMI was positively
      associated with BMI trajectory (coefficient=0.06, P<0.01), whereas high BP and
      high BMI (coefficient=-0.07, P<0.01) or high BP and high BMI and depression
      (coefficient=-0.05, P<0.01) were negatively associated with BMI trajectories.
      CONCLUSIONS: Although physicians' recording of diagnoses for patients with high
      BMI and high BP has improved, significant gaps remain. Some co-occurrence
      patterns of these 3 conditions not only affected the recognition of
      overweight/obesity and hypertension over time, but also BMI trajectories over
      time. Quality improvement efforts should target patients with co-occurring
      depression and overweight/obesity.

PMID- 24561751
TI  - Association between chronic illness complexity and receipt of evidence-based
      depression care.
AB  - BACKGROUND: The rate of guideline concordance with antidepressant treatment for
      persons with depression is low. The problem may be even more pronounced for
      patients with depression and other multiple chronic conditions (MCC). OBJECTIVES:
      To study, for persons with new depressive episodes, the association between MCC
      and the likelihood of receiving guideline-concordant depression treatment.
      RESEARCH DESIGN: Retrospective cohort study using Veterans Affairs administrative
      data. SUBJECTS: A total of 43,189 Veterans Affairs patients who had a new
      depressive episode during 2007 were included. MEASURES: We assessed whether
      patients had an adequate supply of antidepressants during acute and continuation
      phases of depression treatment, which indicates guideline-concordant care. We
      determined the association between comorbid conditions and receipt of adequate
      antidepressant supplies after adjusting for potential confounders. RESULTS:
      Compared with patients with depression alone, those with comorbid
      cardiovascular/cerebrovascular disease, peptic ulcer/gastroesophageal reflux
      disease (GERD), or arthritis were 8%-13% more likely to receive adequate
      antidepressant supplies during the acute phase. Patients with depression and
      substance/alcohol abuse were 15% less likely to receive adequate supplies in the
      acute treatment phase. Those with cardiovascular/cerebrovascular disease or
      peptic ulcer/GERD were 9%-10% more likely to receive continuation phase guideline
      concordant depression treatment. Patients with comorbid substance/alcohol abuse
      were 19% less likely to receive continuation phase guideline-concordant
      depression treatment. Relatively few of the most prevalent MCC clusters were
      significantly associated with receipt of guideline-concordant depression
      treatment. CONCLUSIONS: There was no consistent association between specific
      clusters of chronic conditions and adequate antidepressant supplies. There
      continues to be need for practice-level and system-level interventions to
      increase quality of depression treatment, particularly among persons with certain
      comorbid conditions such as cardiovascular/cerebrovascular disease, peptic
      ulcer/GERD, and arthritis.

PMID- 24561750
TI  - Healthcare task difficulty among older adults with multimorbidity.
AB  - BACKGROUND: Applying disease-specific guidelines to people with multimorbidity
      may result in complex regimens that impose treatment burden. OBJECTIVES: To
      describe and validate a measure of healthcare task difficulty (HCTD) in a sample
      of older adults with multimorbidity. RESEARCH DESIGN: Cross-sectional and
      longitudinal secondary data analysis. SUBJECTS: Multimorbid adults aged 65 years
      or older from primary care clinics. MEASURES: We generated a scale (0-16) of self
      reported difficulty with 8 HCTD and conducted factor analysis to assess its
      dimensionality and internal consistency. To assess predictive ability, cross
      sectional associations of HCTD and number of chronic diseases, and conditions
      that add to health status complexity (falls, visual, and hearing impairment),
      patient activation, patient-reported quality of chronic illness care (Patient
      Assessment of Chronic Illness Care), mental and physical health (SF-36) were
      tested using statistical tests for trend (n=904). Longitudinal analyses of the
      effects of change in HCTD on changes in the outcomes were conducted among a
      subset (n=370) with >=1 follow-up at 6 and/or 18 months. All models were adjusted
      for age, education, sex, race, and time. RESULTS: Greater HCTD was associated
      with worse mental and physical health [Cuzick test for trend (P<0.05)], and
      patient-reported quality of chronic illness care (P<0.05). In longitudinal
      analysis, increasing patient activation was associated with declining HCTD over
      time (P<0.01). Increasing HCTD over time was associated with declining mental
      (P<0.001) and physical health (P=0.001) and patient-reported quality of chronic
      illness care (P<0.05). CONCLUSIONS: The findings of this study establish the
      construct validity of the HCTD scale.

PMID- 24561753
TI  - The Agency for Healthcare Research and Quality Multiple Chronic Conditions
      Research Network: overview of research contributions and future priorities.
AB  - BACKGROUND: By 2030, 171 million Americans are expected to have more than one
      chronic condition. The cohort of individuals with multiple chronic conditions
      (MCC) is growing and two thirds of healthcare costs for the US population are
      currently spent on the 20% of people who have MCC. OBJECTIVES: Recognizing the
      need for increased investment in MCC programs and research, Health and Human
      Services (HHS) developed the HHS Strategic Framework on MCC. The Agency for
      Healthcare Research and Quality (AHRQ) contributed to the goals of the framework
      by funding the MCC Research Network, comprising 45 diverse grants and
      representing one of the largest federal investment in MCC studies to date.
      RESULTS: The initial body of research emerging from the AHRQ MCC Research Network
      included: co-management of commonly co-occurring conditions (including by
      caregivers); care for patients with low-prevalence combinations of MCC; the
      effect of MCC patients on provider performance metrics; guidelines for preventive
      services; medication management in individuals with MCC; as well as MCC-specific
      methodological and analytical techniques. CONCLUSIONS: The authors describe a
      subset of research contributions made in each topic area and make 3
      recommendations for future MCC research: (1) include person-centered and person
      driven measures and outcomes, (2) consider the person in the context of their
      relationships and community, and (3) include mental healthcare as an essential
      part of overall healthcare.

PMID- 24561752
TI  - Comparative effectiveness of two anemia management strategies for complex elderly
      dialysis patients.
AB  - BACKGROUND: Randomized trials found that use of erythropoiesis-stimulating agents
      to target normal hematocrit (Hct) levels (>39%) compared with 27%-34.5% increases
      cardiovascular risk and mortality among chronic kidney disease patients. However,
      the effects of the most widely used Hct target in the past 2 decades, 34.5%-39%,
      have never been examined. OBJECTIVE: To compare the effects of 2 Hct target
      strategies-30.0%-34.5% (low) and 34.5%-39.0% (mid) in a high-risk population:
      elderly dialysis patients with significant comorbidities. RESEARCH DESIGN:
      Observational data from the US Renal Data System were used to emulate a
      randomized trial in which patients were assigned to either Hct strategy. Follow
      up started after completing 3 months of hemodialysis and ended 6 months later. We
      conducted the observational analogs of intention-to-treat and per-protocol
      analyses. Inverse-probability weighting was used to adjust for measured time
      dependent confounding by indication. SUBJECTS: A total of 22,474 elderly patients
      with both diabetes and cardiovascular disease who initiated hemodialysis in 2006
      2008. MEASURES: Hazard ratios (HRs) and survival probabilities for all-cause
      mortality and a composite cardiovascular and mortality endpoint. RESULTS: The
      intention-to-treat HR (95% confidence interval) for mid versus low Hct strategy
      was 1.05 (0.99-1.11) for all-cause mortality and 1.03 (0.98-1.08) for the
      composite endpoint. The per-protocol HR (95% confidence interval) for mid versus
      low Hct strategy was 0.98 (0.78-1.24) for all-cause mortality and 1.00 (0.81
      1.24) for the composite outcome. CONCLUSIONS: Among hemodialysis patients, we did
      not find differences in 6-month survival or cardiovascular risk between clinical
      strategies that target Hct at 30.0%-34.5% versus 34.5%-39.0%.

PMID- 24561754
TI  - Approaches to comparative effectiveness research in multimorbid populations.
AB  - There is an urgent need for an evidence base to guide care for patients with
      multiple chronic medical conditions (MCC). Comparative effectiveness research
      (CER) has been touted as 1 solution to generating such evidence. However, the
      majority of CER topics and methods are designed to generate evidence applicable
      to single diseases. Generating evidence to guide the care of MCC populations
      requires thoughtful, and often alternative, approaches to using the existing
      armamentarium of CER methods. To initiate a dialog about appropriate methods for
      CER in MCC populations, we discuss advantages and disadvantages of experimental
      and quasi-experimental study designs for CER in MCC populations, estimating
      heterogeneity of treatment effects, developing meaningful outcome measures, and
      aligning morbidity measurement with relevant outcomes. Through an engaged dialog
      with clinicians, methodologists, and patients, evidence about strengths and
      limitations of alternative approaches, recommendations about preferred methods
      for CER in MCC can be developed to ensure that knowledge gaps are filled by valid
      evidence. 

PMID- 24561755
TI  - Research on multiple chronic conditions: where we are and where we need to go.

PMID- 24561756
TI  - Costs associated with multimorbidity among VA patients.
AB  - BACKGROUND: Multimorbidity (the presence of multiple chronic conditions) is
      associated with high levels of healthcare utilization and associated costs. We
      investigated the association between number of chronic conditions and costs of
      care for nonelderly and elderly Veterans Affairs (VA) patients, and estimated
      mean VA healthcare costs for the most prevalent and most costly combinations of 3
      conditions (triads). METHODS: We identified a cohort of 5,233,994 patients who
      received care within the VA system in fiscal year 2010. We estimated the costs of
      VA care for each patient using established methods and aggregated costs for
      inpatient care, outpatient care, prescription drugs, and contract care. Using ICD
      9 diagnosis fields from all inpatient and outpatient records, we determined the
      prevalence of 28 chronic conditions and all condition triads. We then compared
      the condition-cost gradient, most prevalent triads, and most costly triads among
      nonelderly (below 65 y) and elderly (65 y and above) patients. RESULTS: Almost
      one third of nonelderly and slightly more than a third of elderly VA patients had
      >=3 conditions, but these patients accounted for 65% and 67% of total VA
      healthcare costs, respectively. The most common triad of chronic conditions for
      both nonelderly and elderly patients was diabetes, hyperlipidemia, and
      hypertension (24% and 29%, respectively). Conditions that were present in the
      most costly triads included spinal cord injury, heart failure, renal failure,
      ischemic heart disease, peripheral vascular disease, stroke, and depression.
      Although patients with the most costly triads had average costs that were 3 times
      higher than average costs among patients with >=3 conditions, the prevalence of
      these costly triads was extremely low (0.1%-0.4%). CONCLUSIONS: Patients with
      multiple chronic conditions account for a disproportionate share of VA healthcare
      expenditures. Interventions that aim to optimize care and contain costs for
      multimorbid patients need to incorporate strategies specific to the most
      prevalent and the most costly combinations of conditions.

PMID- 24561757
TI  - Geographic variation in statin use for complex acute myocardial infarction
      patients: evidence of effective care?
AB  - BACKGROUND: Despite strong evidence to designate statin use for secondary
      prevention of cardiovascular disease (CVD) as "effective care," observational
      studies show that many patients with CVD do not receive statins. This suggests
      that statin prescribing decisions for complex CVD patients are preference
      sensitive. OBJECTIVES: The aim of this study was to evaluate local area variation
      in statin prescribing for subsets of complex patients after acute myocardial
      infarction (AMI) to assess whether current statin prescribing patterns fit
      profiles of either "effective care" or "preference-sensitive care." RESEARCH
      DESIGN AND SUBJECTS: This was a retrospective cohort study of 124,618 Medicare
      patients with fee-for-service parts A, B, and D benefits who were hospitalized
      with AMI in 2008 or 2009 with no evidence of AMI in the past 12 months. MEASURES:
      Patient complexity was defined by the presence of diabetes, heart failure, and
      chronic kidney disease in the year before AMI admission. Local area practice
      styles for "no statin," "lower-intensity statins," and "high-intensity statins"
      were measured using the driving area for clinical care method. Statin prescribing
      rates for complex patient subsets were contrasted across patients grouped by
      local areas practice styles. RESULTS: Lower statin treatment rates were observed
      for patients with complex conditions, especially among those with heart failure.
      However, substantial local area variation in statin prescribing is observed
      across all complex patient groups. CONCLUSIONS: Despite guidelines promoting the
      use of statins for secondary prevention for CVD patients, substantial local area
      variation suggests that patient and provider beliefs and preferences weigh
      heavily in statin prescribing decisions.

PMID- 24561759
TI  - Assessment of morbidity over time in predicting health outcomes.
AB  - BACKGROUND: Administratively derived morbidity measures are often used in
      observational studies as predictors of outcomes. These typically reflect a
      limited time period before an index event; some outcomes may be affected by rate
      of morbidity change over longer preindex periods. OBJECTIVES: The aim of the
      study was to develop statistical models representing the trajectory of individual
      morbidity over time and to evaluate the performance of trajectory versus other
      summary morbidity measures in predicting a range of health outcomes. METHODS:
      From a retrospective cohort study of integrated health system members aged 65
      years or older with 3 or more common chronic medical conditions, we used
      available diagnoses for up to 10 years to examine associations between variations
      of the Charlson Comorbidity Index (CCI, Quan adaptation) and health outcomes. A
      linear mixed effects model was used to estimate the trajectory of individual CCI
      over time; estimated parameters describing individual trajectories were used as
      predictors for health outcomes. Other variations of CCI were: a "snapshot"
      measure, a cumulative measure, and actual baseline and rate of change. Models
      were developed in an initial cohort for whom we had survey data, and verified in
      a larger cohort. RESULTS: Among 961 surveyed members and 13,163 members of a
      secondary cohort, cumulative and snapshot measures provided best fit and
      predictive ability for utilization outcomes. Incorporating trajectory resulted in
      a slightly better model for self-reported health status. CONCLUSIONS: Modeling
      longitudinal morbidity trajectories did not add substantially to the association
      between morbidity and utilization or mortality. Standard snapshot morbidity
      measures likely sufficiently capture multimorbidity in assessing these outcomes.

PMID- 24561758
TI  - Effect of beta-blockers on cardiac and pulmonary events and death in older adults
      with cardiovascular disease and chronic obstructive pulmonary disease.
AB  - CONTEXT: In older adults with multiple conditions, medications may not impart the
      same benefits seen in patients who are younger or without multimorbidity.
      Furthermore, medications given for one condition may adversely affect other
      outcomes. beta-Blocker use with coexisting cardiovascular disease (CVD) and
      chronic obstructive pulmonary disease (COPD) is such a situation. OBJECTIVE: To
      determine the effect of beta-blocker use on cardiac and pulmonary outcomes and
      mortality in older adults with coexisting COPD and CVD. DESIGN, SETTING,
      PARTICIPANTS: The study included 1062 participants who were members of the 2004
      2007 Medicare Current Beneficiary Survey cohorts, a nationally representative
      sample of Medicare beneficiaries. Study criteria included age over 65 years plus
      coexisting CVD and COPD/asthma. Follow-up occurred through 2009. We determined
      the association between beta-blocker use and the outcomes with propensity score
      adjusted and covariate-adjusted Cox proportional hazards. MAIN OUTCOME MEASURES:
      The 3 outcomes were major cardiac events, pulmonary events, and all-cause
      mortality. RESULTS: Half of the participants used beta-blockers. During follow
      up, 179 participants experienced a major cardiac event; 389 participants
      experienced a major pulmonary event; and 255 participants died. Each participant
      could have experienced any >=1 of these events. The hazard ratio for beta-blocker
      use was 1.18 [95% confidence interval (CI), 0.85-1.62] for cardiac events, 0.91
      (95% CI, 0.73-1.12) for pulmonary events, and 0.87 (95% CI, 0.67-1.13) for death.
      CONCLUSION: In this population of older adults, beta-blockers did not seem to
      affect occurrence of cardiac or pulmonary events or death in those with CVD and
      COPD.

PMID- 24561760
TI  - Factors affecting costs in Medicaid populations with behavioral health disorders.
AB  - BACKGROUND: Persons with behavioral disorders incur higher healthcare costs.
      Although they utilize behavioral health (BH) services others do not, they also
      have higher utilization of medical services OBJECTIVES: : To determine the degree
      to which higher costs for persons with BH disorders are attributable to
      utilization of BH services, multiple chronic medical conditions (CMCs) or other
      issues specific to populations with BH disorders. RESEARCH DESIGN: Data base
      consisted of claims for 63,141 Medicaid beneficiaries, 49% of whom had one of 5
      categories of BH disorder. Generalized linear models were used to identify
      relative impact of demographics, BH status, multiple CMCs and primary care access
      on total, behavioral, nonbehavioral, and medical/surgical costs. RESULTS: Number
      of CMCs was associated with significant increases in all cost categories,
      including behavioral costs. Presence of any BH disorder significantly influenced
      these same costs, including those not associated with BH care. Effect size in
      each cost category varied by BH group. CONCLUSIONS: BH status has a large impact
      on all healthcare costs, including costs of medical and other non-BH services.
      The number of CMCs affects BH costs independent of BH disorder. Results suggest
      that costs might be reduced through better integration of behavioral and medical
      health services.

PMID- 24561762
TI  - A conceptual model of the role of complexity in the care of patients with
      multiple chronic conditions.
AB  - BACKGROUND: Effective healthcare for people with multiple chronic conditions
      (MCC) is a US priority, but the inherent complexity makes both research and
      delivery of care particularly challenging. As part of AHRQ Multiple Chronic
      Conditions Research Network (MCCRN) efforts, the Network developed a conceptual
      model to guide research in this area. OBJECTIVE: To synthesize methodological and
      topical issues relevant to MCC patient care into a framework that can improve the
      delivery of care and advance future research about caring for patients with MCC.
      METHODS: The Network synthesized essential constructs for MCC research identified
      from roundtable discussion, input from expert advisors, and previously published
      models. RESULTS: The AHRQ MCCRN conceptual model defines complexity as the gap
      between patient needs and healthcare services, taking into account both the
      multiple considerations that affect the needs of MCC patients, as well as the
      contextual factors that influence service delivery. The model reframes processes
      and outcomes to include not only clinical care quality and experience, but also
      patient health, well being, and quality of life. The single-condition paradigm
      for treating needs one-by-one falls apart and highlights the need for care
      systems to address dynamic patient needs. CONCLUSIONS: Defining complexity in
      terms of the misalignment between patient needs and services offers new insights
      in how to research and develop solutions to patient care needs.

PMID- 24561761
TI  - The fragmentation of hospital use among a cohort of high utilizers: implications
      for emerging care coordination strategies for patients with multiple chronic
      conditions.
AB  - BACKGROUND: Use of multiple hospitals by patients with multiple chronic
      conditions (MCC) may undermine emerging care coordination initiatives. OBJECTIVE:
      The aim of this study was to assess the prevalence and correlates of fragmented
      hospital use among high users with MCC and derive implications for care
      management. RESEARCH DESIGN: Using all-payer hospital billing data, we follow a 2
      year cohort of patients with at least 2 inpatient stays, identifying those with
      MCC and calculating the percentage using multiple hospitals and applying
      multivariate Poisson regression to predict correlates of multiple hospital use.
      SUBJECTS: The subjects included in our study were New Jersey adults with at least
      2 inpatient stays during a 24-month period between 2007 and 2010. RESULTS: Nearly
      80% of the study cohort had >=2 chronic conditions and >30% had fragmented
      hospital use. The probability of visiting multiple hospitals was positively
      associated with the number of chronic conditions present at admission, total
      number of admissions, lower hospital market concentration, and injury or
      behavioral health diagnoses. Over 40% of patients with >=4 stays had multiple
      hospital use. CONCLUSIONS: Fragmentation of hospital care occurs frequently among
      high utilizers with MCC. Although multiple hospital use is not necessarily
      inappropriate, it may present barriers to effective care coordination for complex
      patients with MCC, leading to higher costs or worse outcomes. Leaders of
      innovative delivery reforms such as Accountable Care Organizations should monitor
      and coordinate care for multiple hospital users, especially those with MCC.

PMID- 24561763
TI  - Beyond comorbidity: expanding the definition and measurement of complexity among
      older adults using administrative claims data.
AB  - BACKGROUND: Studies of patients with multiple chronic conditions using claims
      data are often missing important determinants of treatments and outcomes, such as
      function status and disease severity. We sought to identify and evaluate a class
      of function-related indicators (FRIs) from administrative claims data.
      POPULATION: The study cohort comprised US Medicare beneficiaries aged 65 years or
      older with Parts A and B fee-for-service and Part D coverage, with a
      hospitalization for acute myocardial infarction during 2007. METHODS: Measures
      during the year before admission included the FRIs, demographics, conventional
      comorbidity measures, and prior hospitalization. Outcomes were receipt of cardiac
      catheterization during the index hospitalization and 12-month mortality. Model
      development used a random sample (n=72,056) with an equal sample for validation.
      RESULTS: In addition to prior cardiovascular conditions (85%), 40% had >=1
      comorbid condition, 30% were hospitalized in the prior 6 months, and 65% had >=1
      FRI [eg, delirium/dementia (22.7%), depression (16.7%), mobility limitation
      (16.1%), and chronic skin ulcers (12.6%)]. Including the FRIs improved mortality
      and cardiac catheterization prediction models (C-statistics 0.71 and 0.77,
      respectively). Patients with more cardiovascular conditions received less cardiac
      catheterization [minimally adjusted odds ratio (OR) 0.83; 95% confidence interval
      (CI), 0.82-0.83], as did patients with more comorbidities (minimally adjusted OR
      0.70; 95% CI, 0.69-0.71), but this was attenuated by adjusting for functional
      status (fully adjusted OR for cardiovascular conditions 0.95; 95% CI, 0.94-0.96
      and for comorbid conditions 0.94; 95% CI, 0.92-0.95). CONCLUSIONS: Claims data
      studies that include indicators of potentially diminished patient functional
      status better capture heterogeneity of patients with multiple chronic conditions.

PMID- 24561764
TI  - Use of medical homes by patients with comorbid physical and severe mental
      illness.
AB  - BACKGROUND: Patients with comorbid severe mental illness (SMI) may use primary
      care medical homes differently than other patients with multiple chronic
      conditions (MCC). OBJECTIVE: To compare medical home use among patients with
      comorbid SMI to use among those with only chronic physical comorbidities.
      RESEARCH DESIGN: We examined data on children and adults with MCC for fiscal
      years 2008-2010, using generalized estimating equations to assess associations
      between SMI (major depressive disorder or psychosis) and medical home use.
      SUBJECTS: Medicaid and medical home enrolled children (age, 6-17 y) and adults
      (age, 18-64 y) in North Carolina with >=2 of the following chronic health
      conditions: major depressive disorder, psychosis, hypertension, diabetes,
      hyperlipidemia, seizure disorder, asthma, and chronic obstructive pulmonary
      disease. MEASURES: We examined annual medical home participation (>=1 visit to
      the medical home) among enrollees and utilization (number of medical home visits)
      among participants. RESULTS: Compared with patients without depression or
      psychosis, children and adults with psychosis had lower rates of medical home
      participation (-12.2 and -8.2 percentage points, respectively, P<0.01) and lower
      utilization (-0.92 and -1.02 visits, respectively, P<0.01). Children with
      depression had lower participation than children without depression or psychosis
      (-5.0 percentage points, P<0.05). Participation and utilization among adults with
      depression was comparable with use among adults without depression or psychosis
      (P>0.05). CONCLUSIONS: Overall, medical home use was relatively high for Medicaid
      enrollees with MCC, though it was somewhat lower among those with SMI. Targeted
      strategies may be required to increase medical home participation and utilization
      among SMI patients.

PMID- 24561766
TI  - Nanoscale glucan polymer network causes pathogen resistance.
AB  - Successful defence of plants against colonisation by fungal pathogens depends on
      the ability to prevent initial penetration of the plant cell wall. Here we report
      that the pathogen-induced (1,3)-beta-glucan cell wall polymer callose, which is
      deposited at sites of attempted penetration, directly interacts with the most
      prominent cell wall polymer, the (1,4)-beta-glucan cellulose, to form a three
      dimensional network at sites of attempted fungal penetration. Localisation
      microscopy, a super-resolution microscopy technique based on the precise
      localisation of single fluorescent molecules, facilitated discrimination between
      single polymer fibrils in this network. Overexpression of the pathogen-induced
      callose synthase PMR4 in the model plant Arabidopsis thaliana not only enlarged
      focal callose deposition and polymer network formation but also resulted in the
      exposition of a callose layer on the surface of the pre-existing cellulosic cell
      wall facing the invading pathogen. The importance of this previously unknown
      polymeric defence network is to prevent cell wall hydrolysis and penetration by
      the fungus. We anticipate our study to promote nanoscale analysis of plant
      microbe interactions with a special focus on polymer rearrangements in and at the
      cell wall. Moreover, the general applicability of localisation microscopy in
      visualising polymers beyond plant research will help elucidate their biological
      function in complex networks. 

PMID- 24561765
TI  - An improved mechanical testing method to assess bone-implant anchorage.
AB  - Recent advances in material science have led to a substantial increase in the
      topographical complexity of implant surfaces, both on a micro- and a nano-scale.
      As such, traditional methods of describing implant surfaces - namely numerical
      determinants of surface roughness - are inadequate for predicting in vivo
      performance. Biomechanical testing provides an accurate and comparative platform
      to analyze the performance of biomaterial surfaces. An improved mechanical
      testing method to test the anchorage of bone to candidate implant surfaces is
      presented. The method is applicable to both early and later stages of healing and
      can be employed for any range of chemically or mechanically modified surfaces -
      but not smooth surfaces. Custom rectangular implants are placed bilaterally in
      the distal femora of male Wistar rats and collected with the surrounding bone.
      Test specimens are prepared and potted using a novel breakaway mold and the
      disruption test is conducted using a mechanical testing machine. This method
      allows for alignment of the disruption force exactly perpendicular, or parallel,
      to the plane of the implant surface, and provides an accurate and reproducible
      means for isolating an exact peri-implant region for testing.

PMID- 24561767
TI  - The skin prick test is not useful in the diagnosis of the immediate type food
      allergy tolerance acquisition.
AB  - BACKGROUND: Some studies have been reported about positioning of SPT in the
      diagnosis of food allergy. On the other hand, it is not yet clear about the
      positioning of SPT in the diagnosis of tolerance acquisition of the immediate
      type food allergy. METHODS: The retrospective study had been conducted for 236
      egg allergic children (51.3 months in mean), 127 milk allergic children (53.4
      months), and 96 wheat allergic children (42.6 months). The retrospective analysis
      of serum nonspecific and antigen-specific IgE levels, SPT, and OFC had been
      conducted for each allergic patient. All OFC had been conducted to verify the
      acquisition of tolerance against eliminated food. RESULTS: The OFC was positive
      in 61 (25.8%) hen's egg allergies, 34 (26.8%) milk allergies and 33 (34.4%) wheat
      allergies. The greatest AUC for each allergen is as following; hen's egg for egg
      white specific IgE at 0.745, milk/histamine (wheal) index at 0.718, and wheat for
      wheal size at 0.597. For the predictive decision points, the highest accuracy
      rate was at 25.8% for an egg white wheal of 9.5mm, at 26.8% for a milk wheal of
      9.5mm, and at 34.4% for a wheal of 6.5mm. CONCLUSIONS: As a result of this
      analysis, the diagnostic accuracy of SPT had not been satisfactory to judge the
      acquisition of tolerance in allergic children for eggs, milk and wheat.
      Therefore, this is not a strong evidence to testify the tolerance of the
      immediate type food allergy.

PMID- 24561768
TI  - Atopic dermatitis with ichthyosis follicularis, atrichia, and photophobia
      syndrome: a case report.

PMID- 24561769
TI  - Prophylactic effectiveness of suplatast tosilate in children with asthma symptoms
      in the autumn: a pilot study.
AB  - BACKGROUND: Exacerbations of bronchial asthma usually occur in the autumn. To our
      knowledge, however, the effectiveness of drugs for preventing exacerbations of
      asthma in the autumn has not been studied previously, except for leukotriene
      receptor antagonists and Omalizmab. METHODS: This study compared the prophylactic
      effectiveness of suplatast tosilate with that of mequitazine in children with
      asthma symptoms, which is usually exacerbated in the autumn. The study group
      comprised 27 children aged 2 to 15 years who required treatment for asthmatic
      attacks during the past year and tested positive at least for mite allergen in
      the preceding autumn. The subjects were randomly assigned to receive either
      suplatast or mequitazine. The primary endpoint of this study was the number of
      days without symptoms during the 8 weeks of treatment. In addition, the Japanese
      Pediatric Asthma Control Program (JPAC) scores were also recorded every 2 weeks
      in each group. RESULTS: Overall, 14 patients received suplatast, and 13 received
      mequitazine for 8 weeks from September through early October. During follow-up,
      the number of days without symptoms and the total JPAC scores did not differ
      significantly between the groups. However, as compared with weeks 1 to 2 of
      treatment, the mean number of days without symptoms during weeks 7 to 8 increased
      significantly in only the suplatast group (8.6 vs. 11.5 days; p = 0.004).
      CONCLUSIONS: Our results suggest that short-term additional treatment with
      suplatast is useful for preventing asthma symptoms in children with asthma, which
      is usually exacerbated in the autumn.

PMID- 24561770
TI  - The prevalence of asthma diagnosis and symptoms is still increasing in early
      adolescents in Turkey.
AB  - BACKGROUND: This study was performed to evaluate the time trends in prevalence of
      asthma and related factors in Denizli, Turkey. METHODS: Two cross-sectional
      surveys were performed, 6 years apart (2002 and 2008) using the ISAAC protocol,
      in the 13-14 age groups and comparisons were made between the results. RESULTS:
      Lifetime prevalence of wheeze, 12 month prevalence of wheeze, and the prevalence
      of wheeze after exercise in the previous 12 months were significantly increased
      respectively from 10.2% to 13.4% (POR = 1.37, 95%CI = 1.18-1.58, p < 0.001), from
      5.0% to 6.2% (POR = 1.26, 95%CI = 1.02-1.55, p = 0.016) and from 9% to 10.2% (POR
      = 1.15, 95%CI = 0.98-1.35, p = 0.046) in 2008 study. Doctor diagnosed asthma
      prevalence also increased significantly from 2.1% to 12.9 (POR = 6.80, 95%CI =
      5.22-8.85, p < 0.001). Prevalence of sleep disturbed by wheeze in the last 12
      months; but, never woken with wheezing (POR = 1.62, 95%CI = 1.26-2.09, p = <
      0.001) and less than one night per week (POR = 1.58, 95%CI = 1.06-2.36, p =
      0.013) were significantly increased in 2008 study. Severe attacks of wheeze
      limiting speech in the last year was increased from 1.3% to 2.2% (POR = 1.67,
      95%CI = 1.14-2.43, p = 0.004). The number of wheeze attacks in the previous 12
      months was increased significantly for 4-to-12 attacks (POR = 1.54, 95%CI = 1.03
      2.32, p = 0.02) in 2008 study. However, prevalence of waking with cough in the
      last 12 months did not change. While history of family atopy and domestic animal
      at home were found as significant risk factors for asthma in 2002 study, male
      gender, history of family atopy and stuffed toys were found significant in 2008.
      CONCLUSIONS: The prevalence of asthma symptoms were increased in Denizli. History
      of family atopy, male gender and stuffed toys were important risk factors for
      asthma in 2008.

PMID- 24561771
TI  - 'Benifuuki' green tea containing o-methylated catechin reduces symptoms of
      Japanese cedar pollinosis: a randomized, double-blind, placebo-controlled trial.
AB  - BACKGROUND: Methylated catechin, one of the active ingredients in green tea, has
      been reported to ameliorate allergic reactions. We evaluated the efficacy of
      'Benifuuki' green tea, which contains O-methylated epigallocatechin-3-O-[3-O
      methyl] gallate (O-methylated EGCG), in alleviating Japanese cedar pollinosis
      (JCP). METHODS: The study was a double-blind, randomized, placebo-controlled
      trial. The subjects with JCP were randomly assigned to drink 700ml of 'Benifuuki'
      green tea containing O-methylated EGCG or 'Yabukita' green tea (not containing O
      methylated EGCG) as a placebo every day from December 2007 through March 2008,
      which includes the pollen season. The primary outcome was the area under the
      curve (AUC) of symptom scores during the peak pollen season. RESULTS: Fifty-one
      adults with JCP participated in the study. Twenty-six subjects were assigned to
      'Benifuuki' and 25 to 'Yabukita'. The AUC of symptom score during the peak pollen
      season in the 'Benifuuki' group was significantly smaller than in the 'Yabukita'
      group for each of runny nose, itchy eyes, tearing, total nasal symptom score,
      total ocular symptom score, nasal symptom-medication score and ocular symptom
      medication score. The total QOL-related questionnaire score for one week in the
      peak pollen season was significantly better in the 'Benifuuki' group. Increase in
      the peripheral eosinophil count in response to pollen exposure was suppressed in
      the 'Benifuuki' group. No adverse events were reported in either group.
      CONCLUSIONS: 'Benifuuki' green tea containing a large amount of O-methylated EGCG
      reduced the symptoms of JCP and has potential as a complementary/alternative
      medicine for treating seasonal allergic rhinitis.

PMID- 24561772
TI  - Gender, acculturation, and smoking behavior among U.S. Asian and Latino
      immigrants.
AB  - In this paper we examine smoking prevalence and frequency among Asian and Latino
      U.S. immigrants, focusing on how gender differences in smoking behavior are
      shaped by aspects of acculturation and the original decision to migrate. We draw
      on data from 3249 immigrant adults included in the 2002-2003 National Latino and
      Asian American Study. Findings confirm the gender gap in smoking, which is larger
      among Asian than Latino immigrants. While regression models reveal that gender
      differences in smoking prevalence, among both immigrant groups, are not explained
      with adjustment for measures of acculturation and migration decisions, adjustment
      for these factors does reduce gender differences in smoking frequency to non
      significance. Following, we examine gender-stratified models and test whether
      aspects of migration decisions and acculturation relate more strongly to smoking
      behavior among women; we find that patterns are complex and depend upon pan
      ethnic group and smoking measure. 

PMID- 24561773
TI  - Supporting knowledge translation through collaborative translational research
      initiatives: 'bridging' versus 'blurring' boundary-spanning approaches in the UK
      CLAHRC initiative.
AB  - Recent policy initiatives in the UK and internationally have sought to promote
      knowledge translation between the 'producers' and 'users' of research. Within
      this paper we explore how boundary-spanning interventions used within such
      initiatives can support knowledge translation between diverse groups. Using
      qualitative data from a 3-year research study conducted from January 2010 to
      December 2012 of two case-sites drawn from the CLAHRC initiative in the UK, we
      distinguish two different approaches to supporting knowledge translation; a
      'bridging' approach that involves designated roles, discrete events and
      activities to span the boundaries between communities, and a 'blurring' approach
      that de-emphasises the boundaries between groups, enabling a more continuous
      process of knowledge translation as part of day-to-day work-practices. In this
      paper, we identify and differentiate these boundary-spanning approaches and
      describe how they emerged from the context defined by the wider CLAHRC networks.
      This highlights the need to develop a more contextualised analysis of the
      boundary-spanning that underpins knowledge translation processes, relating this
      to the distinctive features of a particular case. 

PMID- 24561775
TI  - Comparing the effects of defaults in organ donation systems.
AB  - The ability of patients in many parts of the world to benefit from
      transplantation is limited by growing shortages of transplantable organs. The
      choice architecture of donation systems is said to play a pivotal role in
      explaining this gap. In this paper we examine the question how different defaults
      affect the decision to register as organ donor. Three defaults in organ donation
      systems are compared: mandated choice, presumed consent and explicit consent.
      Hypothetical choices from a national survey of 2069 respondents in May 2011 in
      the Netherlands - a country with an explicit consent system - suggests that
      mandated choice and presumed consent are more effective at generating registered
      donors than explicit consent. 

PMID- 24561774
TI  - Historical trauma as public narrative: a conceptual review of how history impacts
      present-day health.
AB  - Theories of historical trauma increasingly appear in the literature on individual
      and community health, especially in relation to racial and ethnic minority
      populations and groups that experience significant health disparities. As a
      consequence of this rapid growth, the literature on historical trauma comprises
      disparate terminology and research approaches. This critical review integrates
      this literature in order to specify theoretical mechanisms that explain how
      historical trauma influences the health of individuals and communities. We argue
      that historical trauma functions as a public narrative for particular groups or
      communities that connects present-day experiences and circumstances to the trauma
      so as to influence health. Treating historical trauma as a public narrative
      shifts the research discourse away from an exclusive search for past causal
      variables that influence health to identifying how present-day experiences, their
      corresponding narratives, and their health impacts are connected to public
      narratives of historical trauma for a particular group or community. We discuss
      how the connection between historical trauma and present-day experiences, related
      narratives, and health impacts may function as a source of present-day distress
      as well as resilience. 

PMID- 24561776
TI  - Challenges of health measurement in studies of health disparities.
AB  - Health disparities are increasingly studied in and across a growing array of
      societies. While novel contexts and comparisons are a promising development, this
      commentary highlights four challenges to finding appropriate and adequate health
      measures when making comparisons across groups within a society or across
      distinctive societies. These challenges affect the accuracy with which we
      characterize the degree of inequality, limiting possibilities for effectively
      targeting resources to improve health and reduce disparities. First, comparisons
      may be challenged by different distributions of disease and second, by variation
      in the availability and quality of vital events and census data often used to
      measure health. Third, the comparability of self-reported information about
      specific health conditions may vary across social groups or societies because of
      diagnosis bias or diagnosis avoidance. Fourth, self-reported overall health
      measures or measures of specific symptoms may not be comparable across groups if
      they use different reference groups or interpret questions or concepts
      differently. We explain specific issues that make up each type of challenge and
      show how they may lead to underestimates or inflation of estimated health
      disparities. We also discuss approaches that have been used to address them in
      prior research, note where further innovation is needed to solve lingering
      problems, and make recommendations for improving future research. Many of our
      examples are drawn from South Africa or the United States, societies
      characterized by substantial socioeconomic inequality across ethnic groups and
      wide disparities in many health outcomes, but the issues explored throughout
      apply to a wide variety of contexts and inquiries. 

PMID- 24561782
TI  - Coccygodynia treated by pulsed radio frequency treatment to the Ganglion of
      Impar: a case series.
AB  - BACKGROUND: Chronic coccygodynia accounts for 1% of all back pain referrals and
      very difficult to treat with an enormous functional deficit. OBJECTIVE: The
      purpose of this case series was to examine the effectiveness of pulsed
      radiofrequency treatment to the Ganglion of Impar in chronic coccygodynia
      patients unresponsive to comprehensive medical management. METHODS: Coccygodynia
      is defined as pain in and around the coccyx [1,2]. This retrospective review of
      twenty patients with a clinical diagnosis of coccygodynia and failed medical
      management treated with pulsed radio frequency applied to the Ganglion of Impar
      between January 2009 to December 2011 was carried out. A successful outcome was
      defined as > 50% improvement in pain on the visual analogue scale at 6 and 12
      months follow-up. RESULTS: The application of pulsed radio frequency to the
      Ganglion of Impar was successful in fifteen (75%) patients and their mean pre
      treatment visual analogue scale score of 6.53 was reduced to 0.93 at 6 and 12
      months follow up. In five (25%) patients the treatment was not successful and
      there was no difference between mean pre and post treatment visual analogue scale
      scores. CONCLUSION: We conclude that pulsed radio frequency treatment of the
      Ganglion of Impar should be considered when coccygodynia has proven resistant to
      medical management.

PMID- 24561783
TI  - Influence of walking speed on electromyographic activity of the rectus abdominis
      and erector spinae during high-heeled walking.
AB  - OBJECTIVE: This study aimed to determine the effect of walking speed on the
      electromyographic (EMG) activity of the rectus abdominis (RA) and erector spinae
      (ES) muscles during treadmill high-heeled walking at different shoe heel heights.
      METHODS: Twenty-five young healthy women volunteered to participate in this
      study. The subjects performed treadmill walking at speeds of 3 km/h and 6 km/h
      for 30 seconds under 3 high-heeled conditions: barefoot, 3-cm heels, and 7-cm
      heels. Surface electromyography (EMG) data were collected from standard sites on
      the RA and ES muscles during treadmill walking. RESULTS: For all heel heights,
      the EMG activity of the RA and ES muscles was significantly higher at the 6 km/h
      speed than at the 3 km/h speed (p < 0.05). Furthermore, EMG activity increased
      significantly with increasing shoe heel height, regardless of the walking speed
      (p < 0.05). CONCLUSION: These findings indicate that walking speed and shoe heel
      height may contribute to the increased activity of the trunk muscle during high
      heeled walking. This study provides information for future studies performed with
      the aim of predicting possible changes in trunk muscle activity during high
      heeled walking.

PMID- 24561777
TI  - 'Safer environment interventions': a qualitative synthesis of the experiences and
      perceptions of people who inject drugs.
AB  - There is growing acknowledgment that social, structural, and environmental forces
      produce vulnerability to health harms among people who inject drugs (PWID), and
      safer environment interventions (SEI) have been identified as critical to
      mitigating the impacts of these contextual forces on drug-related harm. To date,
      however, SEIs have been under-theorized in the literature, and how they minimize
      drug-related risks across intervention types and settings has not been adequately
      examined. This article presents findings from a systematic review and meta
      synthesis of qualitative studies reporting PWID's experiences with three types of
      SEIs (syringe exchange programmes, supervised injection facilities and peer-based
      harm reduction interventions) published between 1997 and 2012. This meta
      synthesis sought to develop a comprehensive understanding of SEIs informed by the
      experiences of PWID. Twenty-nine papers representing twenty-one unique studies
      that included an aggregate of more than 800 PWID were included in this meta
      synthesis. This meta-synthesis found that SEIs fostered social and physical
      environments that mitigated drug-related harms and increased access to social and
      material resources. Specifically, SEIs: (1) provided refuge from street-based
      drug scenes; (2) enabled safer injecting by reshaping the social and
      environmental contexts of injection drug use; (3) mediated access to resources
      and health care services; and, (4) were constrained by drug prohibition and law
      enforcement activities. These findings indicate that it is critical to situate
      SEIs in relation to the lived experiences of PWID, and in particular provide
      broader environmental support to PWID. Given that existing drug laws limit the
      effectiveness of interventions, drug policy reforms are needed to enable public
      health, and specifically SEIs, to occupy a more prominent role in the response to
      injection drug use. 

PMID- 24561784
TI  - Association of strength, muscle balance, and atrophy with pain and function in
      patients with degenerative spondylolisthesis.
AB  - PURPOSE: To analyze the relationship of strength, muscular balance, and atrophy
      with pain and function in patients with degenerative spondylolisthesis. STUDY
      DESIGN: Transversal, descriptive, and observational. PATIENTS AND METHODS:
      Institutional review board approval was obtained for this study. Twenty six
      patients ages 50 years and older, with degenerative spondylolisthesis at L4-L5.
      Measurements included Pain Visual Analogue Scale scores (VAS), Oswestry
      Disability Index scores (ODI), and isokinetic trunk testing; assessment of
      multifidus atrophy and spinal stenosis was performed by Magnetic Resonance
      Imaging (MRI). STATISTICS: Statistical analysis was performed using SPSS version
      17.0 software for Windows. Pearson's correlation was used to ascertain the
      correlation between variables. ANOVA with analysis of covariance was used to
      determine the correlation between the remainder variables. Significance was set
      at p < 0.05. RESULTS: Of the 26 patients studied, with an average age of 60.23 +/
      7.6 years, 20 had grade I spondylolisthesis and 6 were grade II. Correlation
      between the ODI scores and spondylolisthesis grading was significant (r=0.576,
      p=0.005); correlation between agonist/antagonist ratio in the isokinetic test
      (predominant extensor muscles over flexors) with the ODI scores was also
      significant (r=0.446, p=0.02), regardless of spinal stenosis. No correlation was
      found between functionality and pain with strength or multifidus atrophy.
      CONCLUSION: Muscle trunk imbalance with predominance of extensor over flexor
      muscles is associated with functional disability. Rehabilitation programs should
      be designed to improve muscle balance rather than muscle strength alone.

PMID- 24561785
TI  - Analysis of the chronic lower limb injuries occurrence in step aerobic
      instructors in relation to their working step class profile: a three year
      longitudinal prospective study.
AB  - BACKGROUND: There is limited information on injury patterns in Step Aerobic
      Instructors (SAI) who exclusively execute "step" aerobic classes. OBJECTIVE: To
      record the type and the anatomical position in relation to diagnosis of muscular
      skeletal injuries in step aerobic instructors. Also, to analyse the days of
      absence due to chronic injury in relation to weekly working hours, height of the
      step platform, working experience and working surface and footwear during the
      step class. METHODS: The Step Aerobic Instructors Injuries Questionnaire was
      developed, and then validity and reliability indices were calculated. 63 SAI
      completed the questionnaire. For the statistical analysis of the data, the method
      used was the analysis of frequencies, the non-parametric test
      chi<formula>^{2}</formula> (chi square distribution), correlation and linear and
      logistic regressions analysis from the SPSS statistical package. RESULTS: 63 SAI
      reported 115 injuries that required more than 2 days absence from step aerobic
      classes. The chronic lower extremity injuries were 73.5%, with the leg pain, the
      anterior knee pain, the plantar tendinopathy and the Achilles tendinopathy being
      most common overuse syndromes. The working hours, the platform height, the years
      of aerobic dance seem to affect the days of absence due to chronic lower limb
      injury occurrence in SAI.

PMID- 24561786
TI  - Activation of the serratus anterior and upper   trapezius in a population with
      winged and   tipped scapulae during push-up-plus and   diagonal shoulder
      elevation.
AB  - OBJECTIVES: Scapular winging and tipping are types of abnormal scapular
      kinematics, which is caused by not only the entrapment of peripheral nerve, but
      also imbalance of the scapulothoracic musculatures. The purpose of this study was
      to investigate the presence of muscular imbalance in the middle and lower parts
      of the serratus anterior and upper trapezius in people with scapular winging and
      tipping. METHODS: Twenty male participants (age, 23.0 +/- 1.92 y) were placed
      into symptomatic group (n = 10) and control group (n = 10). Participants
      completed two individual trials of a push-up plus, and a diagonal shoulder
      elevation, while electromyography (EMG) recorded muscle activity of the low and
      middle serratus anterior and upper trapezius. The root mean squared EMG values
      for three muscles were normalized using maximum voluntary isometric contractions
      (%MVIC). The value was calculated using modified isolation equation for comparing
      activation of middle and lower serratus anterior (%isolation). RESULTS: During a
      diagonal shoulder elevation, the % maximal voluntary isometric contraction
      (%MVIC) data showed that the symptomatic participants had significantly greater
      activation of the middle serratus anterior compared to the control group (P =
      0.01). During a diagonal shoulder elevation, the symptomatic participants had not
      only significantly increased %isolation of the middle serratus anterior, but also
      significantly decreased for the lower serratus anterior compare with the control
      group (p = 0.00). CONCLUSION: Present result indicated that different muscle
      activation between middle and lower serratus anterior could represent in group
      with scapular dyskinesis, and need for selective activation of the lower serratus
      anterior in patients with scapular winging and tipping.

PMID- 24561787
TI  - Investigation of responsiveness indices of generic and specific measures of
      health related quality of life in patients with osteoporosis.
AB  - PURPOSE: To compare responsiveness Short Form-36 (SF-36), Nottingham Health
      Profile (NHP), and QUALEFFO-41 scales in patients diagnosed with osteoporosis.
      METHODS: A number of 70 osteoporosis patients who were in their menopause period
      at least for three years were enrolled in our study. The patients completed Short
      Form-36 (SF-36), Nottingham Health Profile (NHP), and QUALEFFO-41 scales during
      pretreatment period and one year after the termination of the treatment.
      Reponsiveness was compared between questionnaires using standardized
      responsiveness mean (SRM), the effect size (ES), and Guyatt's method. RESULTS:
      All scales revealed statistically significant improvement after the treatment.
      Upon this finding, calculations related with responsiveness indices for SF-36
      (Physical Health and Mental Health), NHP (Total point), and QUALEFFO-41 (Total
      point) demonstrated highly responsive. ES=1.67 and 1.55, SRM=1.55 and 1.85,
      Guyatt value=2.20 and 1.91 for SF-36 Physical Health and Mental Health. ES=1.35,
      SRM=1.35, Guyatt value=1.72 for NHP. QUALEFFO-41's ES=2.56, SRM=4.32 and Guyatt
      value=2.31. CONCLUSION: Osteoporosis specific scale as QUALEFFO-41, gives more
      specific information about the quality of life of osteoporotic patients. If
      patients with osteoporosis will be compared with other diseases regarding quality
      of life, then SF-36, one scale was used to evaluate general quality life of such
      patients, should be preferred against NHP.

PMID- 24561788
TI  - Reliability and validity of lumbar and abdominal trunk muscle endurance tests in
      office workers with nonspecific subacute low back pain.
AB  - BACKGROUND AND OBJECTIVE: Despite the widespread use of trunk endurance tests,
      the reliability and validity of these tests in office workers with subacute
      nonspecific low back pain are unknown. MATERIALS AND METHODS: This cross
      sectional study involved 190 subjects: 30 men and 42 women without low back pain
      and 47 men and 71 women with low back pain. All subjects underwent timed prone
      and supine isometric lumbar and abdominal trunk endurance tests that were
      performed until subjective fatigue occurred. All subjects also completed the
      Roland Morris and Oswestry self-reported disability questionnaires. A test-retest
      study (7 days) was conducted with 31 participants with low back pain from the
      study. RESULTS: For the abdominal trunk endurance test, males and females with
      low back pain had mean (SD) values of 62.06 (36.87) and 46.06 (29.28) seconds,
      respectively, both significantly lower than the asymptomatic workers. For the
      lumbar test, males and females with low back pain had mean (SD) values of 79.57
      (30.66) and 75.49 (28.97) seconds, respectively, again, both significantly lower
      than the asymptomatic workers. The intraclass correlation coefficients of both
      tests exceeded 0.90 and the Kappa indices were excellent for both men and women.
      Receiver-operating curve analyses revealed areas under the curve very close to or
      exceeding 0.70 for both men and women for both tests. CONCLUSIONS: The lumbar and
      abdominal trunk muscle endurance tests appeared to be reliable and valid measures
      in office workers with subacute low back pain.

PMID- 24561789
TI  - Molecular characterization and clinical course of MLL-ACTN4 rearrangement in
      therapy-related hematologic malignancies.

PMID- 24561790
TI  - Hepatitis B or C virus infection and risk of non-Hodgkin lymphoma among solid
      organ transplant recipients.

PMID- 24561791
TI  - Lactotransferrin-Cre reporter mice trace neutrophils, monocytes/macrophages and
      distinct subtypes of dendritic cells.
AB  - Considerable effort has been expended to identify genes that account for myeloid
      lineage commitment and development. However, currently available non-invasive
      mouse models utilize myeloid-specific reporters that are significantly expressed
      in hematopoietic stem cells as well as lymphoid compartments. Here, we describe a
      myeloid-specific marker that is not shared by any other lineage. We show that
      lactotransferrin mRNA is expressed by Gr-1(+)/CD11b(+) cells in the bone marrow,
      as opposed to hematopoietic stem cells or any peripheral cell population. To
      follow the progeny of lactotransferrin-expressing bone marrow cells, we generated
      a mouse model in which a reporter gene is irreversibly activated from the
      lactotransferrin-promoter. We found that lactotransferrin-reporter labels a
      majority of neutrophils, monocytes, macrophages and distinct subtypes of
      dendritic cells, while excluding T, B, natural killer cells, interferon-producing
      killer dendritic cells, plasmacytoid dendritic cells, erythrocytes and
      eosinophils. Lactotransferrin-reporter(-) bone marrow cells retain lymphoid,
      erythroid and long-term repopulating potential, while lactotransferrin
      reporter(+) bone marrow cells confer only myeloid, but not lymphoid potential. We
      conclude that lactotransferrin represents a late stage differentiation marker of
      neutrophils, macrophages and distinct subtypes of dendritic cells. 

PMID- 24561792
TI  - Adult B-cell acute lymphoblastic leukemia cells display decreased PTEN activity
      and constitutive hyperactivation of PI3K/Akt pathway despite high PTEN protein
      levels.
AB  - Adult B-cell acute lymphoblastic leukemia remains a major therapeutic challenge,
      requiring a better characterization of the molecular determinants underlying
      disease progression and resistance to treatment. Here, using a phospho-flow
      cytometry approach we show that adult diagnostic B-cell acute lymphoblastic
      leukemia specimens display PI3K/Akt pathway hyperactivation, irrespective of
      their BCR-ABL status and despite paradoxically high basal expression of PTEN, the
      major negative regulator of the pathway. Protein kinase CK2 is known to
      phosphorylate PTEN thereby driving PTEN protein stabilization and concomitant
      PTEN functional inactivation. In agreement, we found that adult B-cell acute
      lymphoblastic leukemia samples show significantly higher CK2 kinase activity and
      lower PTEN lipid phosphatase activity than healthy controls. Moreover, the
      clinical-grade CK2 inhibitor CX-4945 (Silmitasertib) reversed PTEN levels in
      leukemia cells to those observed in healthy controls, and promoted leukemia cell
      death without significantly affecting normal bone marrow cells. Our studies
      indicate that CK2-mediated PTEN posttranslational inactivation, associated with
      PI3K/Akt pathway hyperactivation, are a common event in adult B-cell acute
      lymphoblastic leukemia and suggest that CK2 inhibition may constitute a valid,
      novel therapeutic tool in this malignancy. 

PMID- 24561794
TI  - Chemotherapy-induced augmentation of T cells expressing inhibitory receptors is
      reversed by treatment with lenalidomide in chronic lymphocytic leukemia.

PMID- 24561793
TI  - Chronic lymphocytic leukemia nurse-like cells express hepatocyte growth factor
      receptor (c-MET) and indoleamine 2,3-dioxygenase and display features of
      immunosuppressive type 2 skewed macrophages.
AB  - Hepatocyte growth factor, produced by stromal and follicular dendritic cells, and
      present at high concentrations in the sera of patients with chronic lymphocytic
      leukemia, prolongs the survival of leukemic B cells by interacting with their
      receptor, c-MET. It is, however, unknown whether hepatocyte growth factor
      influences microenvironmental cells, such as nurse-like cells, which deliver
      survival signals to the leukemic clone. We evaluated the expression of c-MET on
      nurse-like cells and monocytes from patients with chronic lymphocytic leukemia
      and searched for phenotypic/functional features supposed to be influenced by the
      hepatocyte growth factor/c-MET interaction. c-MET is expressed at high levels on
      nurse-like cells and at significantly higher levels than normal on monocytes from
      patients. Moreover, the hepatocyte growth factor/c-MET interaction activates
      STAT3(TYR705) phosphorylation in nurse-like cells. Indoleamine 2,3-dioxygenase,
      an enzyme modulating T-cell proliferation and induced on normal monocytes after
      hepatocyte growth factor treatment, was detected together with interleukin-10 on
      nurse-like cells, and on freshly-prepared patients' monocytes.
      Immunohistochemical/immunostaining analyses demonstrated the presence of c-MET(+)
      and indoleamine 2,3-dioxygenase(+) cells in lymph node biopsies, co-expressed
      with CD68 and vimentin. Furthermore nurse-like cells and chronic lymphocytic
      monocytes significantly inhibited T-cell proliferation, prevented by anti
      transforming growth factor beta and interleukin-10 antibodies and indoleamine 2,3
      dioxygenase inhibitors, and supported CD4(+)CD25(high+)/FOXP3(+) T regulatory
      cell expansion. We suggest that nurse-like cells display features of
      immunosuppressive type 2 macrophages: higher hepatocyte growth factor levels,
      produced by leukemic or other microenvironmental surrounding cells, may cooperate
      to induce M2 polarization. Hepatocyte growth factor may thus have a dual
      pathophysiological role: directly through enhancement of survival of the leukemic
      clone and indirectly by favoring T-cell immunosuppression. 

PMID- 24561795
TI  - A link between the nuclear-localized srGAP3 and the SWI/SNF chromatin remodeler
      Brg1.
AB  - The Slit-Robo GTPase activating protein 3 (srGAP3) is an important modulator of
      actin cytoskeletal dynamics and has an important influence on a variety of
      neurodevelopmental processes. Mutations in the SRGAP3 gene on chromosome 3p25
      have been found in patients with intellectual disability. Genome-wide association
      studies and behavioral assays of knockout mice had also revealed SRGAP3 as a risk
      gene for schizophrenia. We have recently shown that srGAP3 protein undergoes
      regulated shuttling between the cytoplasm and the nucleus during neuronal
      development. It is shown here that nuclear-localized srGAP3 interacts with the
      SWI/SNF remodeling factor Brg1. This interaction is mediated by the C-terminal of
      srGAP3 and the ATPase motif of Brg1. In the primary cultured rat cortical
      neurons, the levels of nuclear-localized srGAP3 and its interaction with Brg1
      have a significant impact on dendrite complexity. Furthermore, the interaction
      between srGAP3 and Brg1 was also involved in valproic acid (VPA) -induced
      neuronal differentiation of Neuro2a cells. We then show that GTP-bound Rac1 and
      GAP-43 may be potential mediators of nuclear srGAP3 and Brg1. Our results not
      only indicate a novel signaling pathway that contributes to neuronal
      differentiation and dendrite morphology, but also implicate a novel molecular
      mechanism underlying srGAP3 regulation of gene expression. 

PMID- 24561796
TI  - Identification of vaccine antigens using integrated proteomic analyses of surface
      immunogens from serogroup B Neisseria meningitidis.
AB  - Meningococcal surface proteins capable of evoking a protective immune response
      are candidates for inclusion in protein-based vaccines against serogroup B
      Neisseria meningitidis (NmB). In this study, a 2-dimensional (2-D) gel-based
      platform integrating surface and immune-proteomics was developed to characterize
      NmB surface protein antigens. The surface proteome was analyzed by differential 2
      D gel electrophoresis following treatment of live bacteria with proteinase K.
      Alongside, proteins recognized by immune sera from mice challenged with live
      meningococci were detected using 2-D immunoblots. In combination, seventeen
      proteins were identified including the well documented antigens PorA, OpcA and
      factor H-binding protein, previously reported potential antigens and novel
      potential immunogens. Results were validated for the macrophage infectivity
      potentiator (MIP), a recently proposed NmB vaccine candidate. MIP-specific
      antisera bound to meningococci in whole-cell ELISA and facilitated
      opsonophagocytosis and deposition of complement factors on the surface of
      meningococcal isolates of different serosubtypes. Cleavage by proteinase K was
      confirmed in western blots and shown to occur in a fraction of the MIP expressed
      by meningococci suggesting transient or limited surface exposure. These
      observations add knowledge for the development of a protein NmB vaccine. The
      proteomic workflow presented here may be used for the discovery of vaccine
      candidates against other pathogens. BIOLOGICAL SIGNIFICANCE: This study presents
      an integrated proteomic strategy to identify proteins from N. meningitidis with
      desirable properties (i.e. surface exposure and immunogenicity) for inclusion in
      subunit vaccines against bacterial meningitis. The effectiveness of the method
      was demonstrated by the identification of some of the major meningococcal vaccine
      antigens. Information was also obtained about novel potential immunogens as well
      as the recently described potential antigen macrophage infectivity potentiator
      which can be useful for its consideration as a vaccine candidate. Additionally,
      the proteomic strategy presented in this study provides a generic 2-D gel-based
      platform for the discovery of vaccine candidates against other bacterial
      infections.

PMID- 24561797
TI  - Surface analysis of Dicrocoelium dendriticum. The molecular characterization of
      exosomes reveals the presence of miRNAs.
AB  - With the aim of characterizing the molecules involved in the interaction of
      Dicrocoelium dendriticum adults and the host, we have performed proteomic
      analyses of the external surface of the parasite using the currently available
      datasets including the transcriptome of the related species Echinostoma caproni.
      We have identified 182 parasite proteins on the outermost surface of D.
      dendriticum. The presence of exosome-like vesicles in the ESP of D. dendriticum
      and their components has also been characterized. Using proteomic approaches, we
      have characterized 84 proteins in these vesicles. Interestingly, we have detected
      miRNA in D. dendriticum exosomes, thus representing the first report of miRNA in
      helminth exosomes. BIOLOGICAL SIGNIFICANCE: In order to identify potential
      targets for intervention against parasitic helminths, we have analyzed the
      surface of the parasitic helminth Dicrocoelium dendriticum. Along with the
      proteomic analyses of the outermost layer of the parasite, our work describes the
      molecular characterization of the exosomes of D. dendriticum. Our proteomic data
      confirm the improvement of protein identification from "non-model organisms" like
      helminths, when using different search engines against a combination of available
      databases. In addition, this work represents the first report of miRNAs in
      parasitic helminth exosomes. These vesicles can pack specific proteins and RNAs
      providing stability and resistance to RNAse digestion in body fluids, and provide
      a way to regulate host-parasite interplay. The present data should provide a
      solid foundation for the development of novel methods to control this non-model
      organism and related parasites. This article is part of a Special Issue entitled:
      Proteomics of non-model organisms.

PMID- 24561799
TI  - An Uncommon Cause of Facial Nerve Palsy: Glomus Jugulare.

PMID- 24561800
TI  - The Influence of Electrolarynx Use on Postlaryngectomy Voice-Related Quality of
      Life.
AB  - OBJECTIVE: To investigate voice-related quality of life in an effort to index
      self-assessed voice disability in speakers who use the electrolarynx and to
      determine the perceived level of influence of the electrolarynx on vocal
      communication. STUDY DESIGN: Prospective study. SETTING: This study was conducted
      at a tertiary care facility. SUBJECTS AND METHODS: Forty laryngectomized adults
      (25 men, 15 women) who used the electrolarynx as a primary method of
      communication served as participants. The Voice-Related Quality of Life measure
      was administered and scored in standard fashion and descriptive data generated
      for physical, social-emotional, and total scores. RESULTS: Data indicate
      substantial variability in self-perceived quality of life specific to voice use;
      a wide range of physical, social-emotional, and total scores were observed. Only
      one-quarter of these participants rated themselves as having "poor/fair" voice
      related quality of life. CONCLUSION: Our findings suggest that use of the
      electrolarynx as a postlaryngectomy method of verbal communication has a wide
      ranging influence on self-perceived voice-related quality of life and that mean
      scores from prior studies may not accurately reflect the potential value of the
      electrolarynx. Communication disability related to electrolarynx use does in fact
      vary; however, it is not uniformly poor, and some may be highly proficient users.
      Consequently, the Voice-Related Quality of Life measure may also serve as a
      useful tool for clinical documentation of rehabilitation outcomes in those who
      use the electrolarynx as a postlaryngectomy method of speech.

PMID- 24561801
TI  - Methods for studying the mechanisms of action of antipsychotic drugs in
      Caenorhabditis elegans.
AB  - Caenorhabditis elegans is a simple genetic organism amenable to large-scale
      forward and reverse genetic screens and chemical genetic screens. The C. elegans
      genome includes potential antipsychotic drug (APD) targets conserved in humans,
      including genes encoding proteins required for neurotransmitter synthesis and for
      synaptic structure and function. APD exposure produces developmental delay and/or
      lethality in nematodes in a concentration-dependent manner. These phenotypes are
      caused, in part, by APD-induced inhibition of pharyngeal pumping(1,2). Thus, the
      developmental phenotype has a neuromuscular basis, making it useful for
      pharmacogenetic studies of neuroleptics. Here we demonstrate detailed procedures
      for testing APD effects on nematode development and pharyngeal pumping. For the
      developmental assay, synchronized embryos are placed on nematode growth medium
      (NGM) plates containing APDs, and the stages of developing animals are then
      scored daily. For the pharyngeal pumping rate assay, staged young adult animals
      are tested on NGM plates containing APDs. The number of pharyngeal pumps per unit
      time is recorded, and the pumping rate is calculated. These assays can be used
      for studying many other types of small molecules or even large molecules. 

PMID- 24561802
TI  - Radial symmetry in a chimeric glutamate receptor pore.
AB  - Ionotropic glutamate receptors comprise two conformationally different A/C and
      B/D subunit pairs. Closed channels exhibit fourfold radial symmetry in the
      transmembrane domain (TMD) but transition to twofold dimer-of-dimers symmetry for
      extracellular ligand binding and N-terminal domains. Here, to evaluate symmetry
      in open pores we analysed interaction between the Q/R editing site near the pore
      loop apex and the transmembrane M3 helix of kainate receptor subunit GluK2.
      Chimeric subunits that combined the GluK2 TMD with extracellular segments from
      NMDA receptors, which are obligate heteromers, yielded channels made up of A/C
      and B/D subunit pairs with distinct substitutions along M3 and/or Q/R site
      editing status, in an otherwise identical homotetrameric TMD. Our results
      indicate that Q/R site interaction with M3 occurs within individual subunits and
      is essentially the same for both A/C and B/D subunit conformations, suggesting
      that fourfold pore symmetry persists in the open state. 

PMID- 24561804
TI  - A non-canonical plant microRNA target site.
AB  - Plant microRNAs (miRNAs) typically form near-perfect duplexes with their targets
      and mediate mRNA cleavage. Here, we describe an unconventional miRNA target of
      miR398 in Arabidopsis, an mRNA encoding the blue copper-binding protein (BCBP).
      BCBP mRNA carries an miR398 complementary site in its 5'-untranslated region
      (UTR) with a bulge of six nucleotides opposite to the 5' region of the miRNA.
      Despite the disruption of a target site region thought to be especially critical
      for function, BCBP mRNAs are cleaved by ARGONAUTE1 between nucleotides 10th and
      11th, opposite to the miRNA, like conventional plant target sites. Levels of BCBP
      mRNAs are inversely correlated to levels of miR398 in mutants lacking the miRNA,
      or transgenic plants overexpressing it. Introducing two mutations that disrupt
      the miRNA complementarity around the cleavage site renders the target cleavage
      resistant. The BCBP site functions outside of the context of the BCBP mRNA and
      does not depend on 5'-UTR location. Reducing the bulge does not interfere with
      miR398-mediated regulation and completely removing it increases the efficiency of
      the slicing. Analysis of degradome data and target predictions revealed that the
      miR398-BCBP interaction seems to be rather unique. Nevertheless, our results
      imply that functional target sites with non-perfect pairings in the 5' region of
      an ancient conserved miRNA exist in plants. 

PMID- 24561805
TI  - Tissue specific CTCF occupancy and boundary function at the human growth hormone
      locus.
AB  - The robust and tissue-specific activation of the human growth hormone (hGH) gene
      cluster in the pituitary and placenta constitutes an informative model for
      analysis of gene regulation. The five-gene hGH cluster is regulated by two
      partially overlapping sets of DNase I hypersensitive sites (HSs) that constitute
      the pituitary (HSI, II, III and V) and placental (HSIII, IV, and V) locus control
      regions (LCRs). The single placenta-specific LCR component, HSIV, is located at 
      30 kb to the cluster. Here we generate a series of hGH/BAC transgenes
      specifically modified to identify structural features of the hGH locus required
      for its appropriate placental expression. We find that placental specificity is
      dependent on the overall multigene configuration of the cluster whereas the
      distance between the cluster and its LCR impacts the level of placental
      expression. We further observe that a major function of the placental hGH LCR is
      to insulate the transgene locus from site-of-integration effects. This insulation
      activity is linked to placenta-specific occupancy of the chromatin architectural
      protein, CTCF, at HSIV. These data reveal a remarkable combination of structural
      configurations and regulatory determinants that must work in concert to insure
      robust and tightly controlled expression from a complex multigene locus. 

PMID- 24561803
TI  - Histone H3 phosphorylation near the nucleosome dyad alters chromatin structure.
AB  - Nucleosomes contain ~146 bp of DNA wrapped around a histone protein octamer that
      controls DNA accessibility to transcription and repair complexes.
      Posttranslational modification (PTM) of histone proteins regulates nucleosome
      function. To date, only modest changes in nucleosome structure have been directly
      attributed to histone PTMs. Histone residue H3(T118) is located near the
      nucleosome dyad and can be phosphorylated. This PTM destabilizes nucleosomes and
      is implicated in the regulation of transcription and repair. Here, we report gel
      electrophoretic mobility, sucrose gradient sedimentation, thermal disassembly,
      micrococcal nuclease digestion and atomic force microscopy measurements of two
      DNA-histone complexes that are structurally distinct from nucleosomes. We find
      that H3(T118ph) facilitates the formation of a nucleosome duplex with two DNA
      molecules wrapped around two histone octamers, and an altosome complex that
      contains one DNA molecule wrapped around two histone octamers. The nucleosome
      duplex complex forms within short ~150 bp DNA molecules, whereas altosomes
      require at least ~250 bp of DNA and form repeatedly along 3000 bp DNA molecules.
      These results are the first report of a histone PTM significantly altering the
      nucleosome structure. 

PMID- 24561806
TI  - Molecular basis for the wide range of affinity found in Csr/Rsm protein-RNA
      recognition.
AB  - The carbon storage regulator/regulator of secondary metabolism (Csr/Rsm) type of
      small non-coding RNAs (sRNAs) is widespread throughout bacteria and acts by
      sequestering the global translation repressor protein CsrA/RsmE from the ribosome
      binding site of a subset of mRNAs. Although we have previously described the
      molecular basis of a high affinity RNA target bound to RsmE, it remains unknown
      how other lower affinity targets are recognized by the same protein. Here, we
      have determined the nuclear magnetic resonance solution structures of five
      separate GGA binding motifs of the sRNA RsmZ of Pseudomonas fluorescens in
      complex with RsmE. The structures explain how the variation of sequence and
      structural context of the GGA binding motifs modulate the binding affinity for
      RsmE by five orders of magnitude (~10 nM to ~3 mM, Kd). Furthermore, we see that
      conformational adaptation of protein side-chains and RNA enable recognition of
      different RNA sequences by the same protein contributing to binding affinity
      without conferring specificity. Overall, our findings illustrate how the
      variability in the Csr/Rsm protein-RNA recognition allows a fine-tuning of the
      competition between mRNAs and sRNAs for the CsrA/RsmE protein. 

PMID- 24561807
TI  - The contribution of mitochondrial thymidylate synthesis in preventing the nuclear
      genome stress.
AB  - In quiescent fibroblasts, the expression levels of cytosolic enzymes for
      thymidine triphosphate (dTTP) synthesis are down-regulated, causing a marked
      reduction in the dTTP pool. In this study, we provide evidence that mitochondrial
      thymidylate synthesis via thymidine kinase 2 (TK2) is a limiting factor for the
      repair of ultraviolet (UV) damage in the nuclear compartment in quiescent
      fibroblasts. We found that TK2 deficiency causes secondary DNA double-strand
      breaks formation in the nuclear genome of quiescent cells at the late stage of
      recovery from UV damage. Despite slower repair of quiescent fibroblast deficient
      in TK2, DNA damage signals eventually disappeared, and these cells were capable
      of re-entering the S phase after serum stimulation. However, these cells
      displayed severe genome stress as revealed by the dramatic increase in 53BP1
      nuclear body in the G1 phase of the successive cell cycle. Here, we conclude that
      mitochondrial thymidylate synthesis via TK2 plays a role in facilitating the
      quality repair of UV damage for the maintenance of genome integrity in the cells
      that are temporarily arrested in the quiescent state. 

PMID- 24561808
TI  - Deciphering the rules by which dynamics of mRNA secondary structure affect
      translation efficiency in Saccharomyces cerevisiae.
AB  - Messenger RNA (mRNA) secondary structure decreases the elongation rate, as
      ribosomes must unwind every structure they encounter during translation.
      Therefore, the strength of mRNA secondary structure is assumed to be reduced in
      highly translated mRNAs. However, previous studies in vitro reported a positive
      correlation between mRNA folding strength and protein abundance. The
      counterintuitive finding suggests that mRNA secondary structure affects
      translation efficiency in an undetermined manner. Here, we analyzed the folding
      behavior of mRNA during translation and its effect on translation efficiency. We
      simulated translation process based on a novel computational model, taking into
      account the interactions among ribosomes, codon usage and mRNA secondary
      structures. We showed that mRNA secondary structure shortens ribosomal distance
      through the dynamics of folding strength. Notably, when adjacent ribosomes are
      close, mRNA secondary structures between them disappear, and codon usage
      determines the elongation rate. More importantly, our results showed that the
      combined effect of mRNA secondary structure and codon usage in highly translated
      mRNAs causes a short ribosomal distance in structural regions, which in turn
      eliminates the structures during translation, leading to a high elongation rate.
      Together, these findings reveal how the dynamics of mRNA secondary structure
      coupling with codon usage affect translation efficiency. 

PMID- 24561809
TI  - A Bayesian hierarchical model to detect differentially methylated loci from
      single nucleotide resolution sequencing data.
AB  - DNA methylation is an important epigenetic modification that has essential roles
      in cellular processes including gene regulation, development and disease and is
      widely dysregulated in most types of cancer. Recent advances in sequencing
      technology have enabled the measurement of DNA methylation at single nucleotide
      resolution through methods such as whole-genome bisulfite sequencing and reduced
      representation bisulfite sequencing. In DNA methylation studies, a key task is to
      identify differences under distinct biological contexts, for example, between
      tumor and normal tissue. A challenge in sequencing studies is that the number of
      biological replicates is often limited by the costs of sequencing. The small
      number of replicates leads to unstable variance estimation, which can reduce
      accuracy to detect differentially methylated loci (DML). Here we propose a novel
      statistical method to detect DML when comparing two treatment groups. The
      sequencing counts are described by a lognormal-beta-binomial hierarchical model,
      which provides a basis for information sharing across different CpG sites. A Wald
      test is developed for hypothesis testing at each CpG site. Simulation results
      show that the proposed method yields improved DML detection compared to existing
      methods, particularly when the number of replicates is low. The proposed method
      is implemented in the Bioconductor package DSS. 

PMID- 24561810
TI  - An improved method for accurate and rapid measurement of flight performance in
      Drosophila.
AB  - Drosophila has proven to be a useful model system for analysis of behavior,
      including flight. The initial flight tester involved dropping flies into an oil
      coated graduated cylinder; landing height provided a measure of flight
      performance by assessing how far flies will fall before producing enough thrust
      to make contact with the wall of the cylinder. Here we describe an updated
      version of the flight tester with four major improvements. First, we added a
      "drop tube" to ensure that all flies enter the flight cylinder at a similar
      velocity between trials, eliminating variability between users. Second, we
      replaced the oil coating with removable plastic sheets coated in Tangle-Trap, an
      adhesive designed to capture live insects. Third, we use a longer cylinder to
      enable more accurate discrimination of flight ability. Fourth we use a digital
      camera and imaging software to automate the scoring of flight performance. These
      improvements allow for the rapid, quantitative assessment of flight behavior,
      useful for large datasets and large-scale genetic screens. 

PMID- 24561811
TI  - Muscle atrophy, pain, and damage in bed rest reduced by resistive (vibration)
      exercise.
AB  - The purpose of this study was to investigate the effectiveness of a short
      duration (5-6 min, 3 d.wk) resistive exercise program with (RVE) or without (RE)
      whole-body vibration in reducing muscle atrophy in the lower limb during
      prolonged inactivity when compared with that in an inactive control group.
      METHODS: As part of the second Berlin BedRest Study, 24 male subjects underwent
      60 d of head-down tilt bed rest. Using magnetic resonance imaging, muscle volumes
      of the individual muscles of the lower limb were calculated before and at various
      intervals during and after bed rest. Pain levels and markers of muscle damage
      were also evaluated during and after bed rest. Adjustment of P values to guard
      against false positives was performed via the false discovery rate method.
      RESULTS: On the "intent-to-treat" analysis, RE reduced atrophy of the medial and
      lateral gastrocnemius, soleus, vasti, tibialis posterior, flexor hallucis longus,
      and flexor digitorum longus (P <= 0.045 vs control group) and RVE reduced atrophy
      of the medial and lateral gastrocnemius and tibialis posterior (P <= 0.044). Pain
      intensity reports after bed rest were lower in RE at the foot (P <= 0.033) and
      whole lower limb (P = 0.01) and in RVE at the thigh (P <= 0.041), lower leg (P <=
      0.01), and whole lower limb (P <= 0.036). Increases in sarcomere-specific
      creatine kinase after bed rest were less in RE (P = 0.020) and RVE (P = 0.020).
      No differences between RE and RVE were observed. CONCLUSIONS: In conclusion, a
      short-duration RVE or RE can be effective in reducing the effect of prolonged bed
      rest on lower extremity muscle volume loss during bed rest and muscle damage and
      pain after bed rest.

PMID- 24561812
TI  - Quercetin enhances exercise-mediated neuroprotective effects in brain ischemic
      rats.
AB  - PURPOSE: Reactive oxygen species are markedly increased after ischemia and play
      important roles in the mechanism of ischemia-reperfusion injury. Regulating the
      oxidative stress response after brain ischemia provides a potential therapeutic
      strategy. Quercetin is a natural flavonoid that exhibits antioxidant properties.
      However, the mechanisms by which it protects cells are not fully understood.
      Exercise training also reduces oxidative stress and enhances brain recovery. The
      purpose of this study was to determine whether combined exercise training with
      quercetin treatment could result in better neuroprotection and functional
      recovery in rats subjected to brain ischemia. METHODS: Rats were randomly
      assigned to the following groups: middle cerebral artery occlusion (MCAO) with
      rest control, MCAO with quercetin, MCAO with exercise, or MCAO with exercise and
      quercetin. To determine the effect of PI3K/Akt pathway in quercetin and exercise
      mediated neuroprotection, two additional groups, a group of MCAO with quercetin
      and PI3K/Akt inhibitor (LY294002) and a group of MCAO with exercise, quercetin,
      and PI3K/Akt inhibitor, were added in this study. Motor function was examined at
      the 24th hour and 14th day post-MCAO. Brain samples were used to measure the
      expression of antioxidative and antiapoptotic proteins as well as to measure the
      infarct volume. RESULTS: Treatment with either exercise or quercetin
      significantly decreased oxidative stress and infarct volume, increased
      antioxidative and antiapoptotic signaling, and improved motor function. Exercise
      training combined with quercetin treatment resulted in better outcomes than
      either treatment alone. PI3K/Akt inhibition eliminated the protective effects of
      exercise training and quercetin treatment. CONCLUSION: Quercetin enhances
      exercise-mediated functional recovery after brain ischemia via up-regulation of
      PI3K/Akt activity to promote antioxidative and antiapoptotic signaling.

PMID- 24561813
TI  - Respiratory muscle power and the slow component of O2 uptake.
AB  - PURPOSE: The slow component of O2 uptake (VO2sc) represents a progressive decline
      in work efficiency during strenuous, constant work rate cycling. Although most of
      this "excess" O2 uptake can be explained by factors intrinsic to the exercising
      muscles, it has been proposed that respiratory muscle work rate may also
      contribute to the VO2sc response. To date, however, no study has provided a
      comprehensive analysis of the mechanical power of breathing (Pb) in relation to
      the VO2sc while performing strenuous exercise. METHODS: The mechanical Pb was
      measured in 12 recreational cyclists (24 +/- 1 yr, 70.9 +/- 3.9 kg) during heavy-
      and severe-intensity cycling. The resistive and elastic components of Pb were
      quantified using the modified Campbell diagram. RESULTS: Total Pb significantly
      increased (P < 0.05) over the VO2sc phase during both heavy (Delta13 +/- 2 J.min)
      and severe work rate transitions (Delta219 +/- 56 J.min). The magnitude of this
      increase was relatively greater during severe cycling trials (P < 0.05). The
      greater "slow component" rise in total Pb during severe work rate transitions was
      consequent to relatively larger increases in the inspiratory and expiratory
      resistive Pb and inspiratory elastic Pb (P < 0.05). CONCLUSIONS: The findings of
      this investigation support the thesis that the energetic contribution from
      respiratory muscles to the VO2sc amplitude is disproportionately higher during
      severe- compared with that during heavy-intensity exercise.

PMID- 24561814
TI  - Cardiac autonomic function and high-intensity interval training in middle-age
      men.
AB  - PURPOSE: The effects of short-term high-intensity interval training (HIT) on
      cardiac autonomic function are unclear. The present study assessed cardiac
      autonomic adaptations to short-term HIT in comparison with aerobic endurance
      training (AET). METHODS: Twenty-six healthy middle-age sedentary men were
      randomized into HIT (n = 13, 4-6 * 30 s of all-out cycling efforts with 4-min
      recovery) and AET (n = 13, 40-60 min at 60% of peak workload) groups, performing
      six sessions within 2 wk. The participants underwent a 24-h ECG recording before
      and after the intervention and, additionally, recorded R-R interval data in
      supine position (5 min) at home every morning during the intervention. Mean HR
      and low-frequency (LF) and high-frequency (HF) power of R-R interval oscillation
      were analyzed from these recordings. RESULTS: Peak oxygen consumption (VO2peak)
      increased in both groups (P < 0.001). Compared with AET (n = 11), HIT (n = 13)
      increased 24-h LF power (P = 0.024), tended to increase 24-h HF power (P =
      0.068), and increased daytime HF power (P = 0.038). In home-based measurements,
      supine HF power decreased on the days after HIT (P = 0.006, n = 12) but not AET
      (P = 0.80, n = 9) session. The acute response of HF power to HIT session did not
      change during the intervention. CONCLUSIONS: In conclusion, HIT was more
      effective short-term strategy to increase R-R interval variability than aerobic
      training, most probably by inducing larger increases in cardiac vagal activity.
      The acute autonomic responses to the single HIT session were not modified by
      short-term training.

PMID- 24561815
TI  - Postexercise muscle cooling enhances gene expression of PGC-1alpha.
AB  - PURPOSE: This study aimed to investigate the influence of localized muscle
      cooling on postexercise vascular, metabolic, and mitochondrial-related gene
      expression. METHODS: Nine physically active males performed 30 min of continuous
      running at 70% of their maximal aerobic velocity, followed by intermittent
      running to exhaustion at 100% maximal aerobic velocity. After exercise, subjects
      immersed one leg in a cold water bath (10 degrees C, COLD) to the level of their
      gluteal fold for 15 min. The contralateral leg remained outside the water bath
      and served as control (CON). Core body temperature was monitored throughout the
      experiment, whereas muscle biopsies and muscle temperature (Tm) measurements were
      obtained from the vastus lateralis before exercise (PRE), immediately
      postexercise (POST-EX, Tm only), immediately after cooling, and 3 h postexercise
      (POST-3H). RESULTS: Exercise significantly increased core body temperature (PRE,
      37.1 degrees C +/- 0.4 degrees C vs POST-EX, 39.3 degrees C +/- 0.5 degrees C, P
      < 0.001) and Tm in both CON (PRE, 33.9 degrees C +/- 0.7 degrees C vs POST-EX,
      39.1 degrees C +/- 0.5 degrees C) and COLD legs (PRE, 34.2 degrees C +/- 0.9
      degrees C vs POST-EX, 39.4 degrees C +/- 0.3 degrees C), respectively (P <
      0.001). After cooling, Tm was significantly lower in COLD (28.9 degrees C +/- 2.3
      degrees C vs 37.0 degrees C +/- 0.8 degrees C, P < 0.001) whereas PGC-1alpha
      messenger RNA expression was significantly higher in COLD at POST-3H (P = 0.014).
      Significant time effects were evident for changes in vascular endothelial growth
      factor (P = 0.038) and neuronal nitric oxide synthase (P = 0.019) expression.
      However, no significant condition effects between COLD and CON were evident for
      changes in both vascular endothelial growth factor and neuronal nitric oxide
      synthase expressions. CONCLUSIONS: These data indicate that an acute postexercise
      cooling intervention enhances the gene expression of PGC-1alpha and may therefore
      provide a valuable strategy to enhance exercise-induced mitochondrial biogenesis.

PMID- 24561816
TI  - Physiological responses to diesel exhaust exposure are modified by cycling
      intensity.
AB  - BACKGROUND: Outdoor exercisers are frequently exposed to diesel exhaust (DE) that
      contains particulate matter (PM) air pollution. How the respiratory and metabolic
      responses to exercise are affected by DE exposure and how these responses change
      with exercise intensity are unknown. PURPOSE: This study aimed to determine the
      respiratory and metabolic responses to low- and high-intensity cycling with DE
      exposure containing high levels of PM. METHODS: Eighteen males age 24.5 +/- 6.2
      yr performed 30-min trials of low-intensity (30% of power at VO2peak) and high
      intensity (60% of power at VO2peak) cycling as well as rest. Each trial was
      performed once while breathing filtered air (FA) and once while breathing DE (300
      MUg.m of PM2.5) for a total of six trials, each separated by 7 d. During the
      trials, minute ventilation (VE), oxygen consumption (VO2), CO2 production (VCO2),
      RER, and perceived exertion for lungs (RPELungs) and legs (RPELegs) were
      measured. Work of breathing, respiratory muscle VO2, ratio of O2 consumption to
      power output, and gross efficiency were estimated. RESULTS: The RER was
      significantly lower (0.02 lower, P = 0.008), and the RPELungs (0.9 greater, P =
      0.001) and the RPELegs (0.6 greater, P = 0.017) were significantly greater, in DE
      compared with FA. During low-intensity exercise, VE (44.5 +/- 8.9 vs 40.5 +/- 8.0
      L.min, P < 0.001), VO2 (27.9 +/- 5.4 vs 24.9 +/- 4.4 mL.kg.min, P = 0.001), and
      VCO2 (25.9 +/- 5.3 vs 23.5 +/- 4.5 mL.kg.min, P = 0.006) were significantly
      greater in DE. This pattern was not seen during high-intensity cycling.
      CONCLUSIONS: Respiratory and metabolic responses to low-intensity, but not high
      intensity, cycling in DE exceed FA. Practically, the greater responses during low
      intensity exercise in DE could have implications for individuals with
      cardiopulmonary disease. Also, the elevated RPE during DE could impair
      performance in self-paced exercise.

PMID- 24561817
TI  - Circulating endothelial cells in children: role of fitness, activity, and
      adiposity.
AB  - PURPOSE: Circulating endothelial cells (CEC) are thought to be useful biomarkers
      of endothelial dysfunction and overall cardiovascular health. The extent to which
      CEC are influenced by fitness, physical activity, and adiposity in youth remains
      unknown, as they have seldom been examined in the pediatric population. This
      study assessed resting levels of CEC in boys and girls of different chronological
      and biological age and explored the relationship between these cells and aerobic
      fitness, physical activity, and adiposity. METHODS: Seventy-five children (39
      males; median [interquartile range], age = 14.4 [5.8]) completed two study
      visits. During the first visit, basic anthropometric data were collected and
      biological age was calculated. Peak mechanical power (Wpeak) was determined using
      the McMaster All-Out Continuous cycling test. Participants then wore an
      accelerometer over a 7-d period to assess habitual levels of moderate-to-vigorous
      physical activity. During visit 2, percent body fat (%BF) was assessed by dual
      energy x-ray absorptiometry. A fasted blood sample was also collected from which
      concentrations of CEC, identified as CD31CD34CD45CD133, were quantified by flow
      cytometry. RESULTS: No differences were seen in CEC by sex, chronological age, or
      biological age. The median (interquartile range) CEC concentration was 32.3 * 10
      (63.0 * 10), representing 1.3% (2.7%) of collected peripheral blood mononuclear
      cells. CEC concentration was associated with Wpeak normalized to lean body mass
      (r = 0.36, P < 0.01) and time spent in moderate-to-vigorous physical activity (r
      = -0.27, P = 0.02). No relationship was observed between CEC and %BF. CONCLUSION:
      Healthy children demonstrate relatively low concentrations of CECs. Because CEC
      represent a population of mature endothelial cells shed from the intima after
      irreversible damage, they may be more reflective of recent physical activity
      levels rather than fitness or level of adiposity.

PMID- 24561819
TI  - The valid measurement of running economy in runners.
AB  - Oxygen cost (OC) is commonly used to assess an athlete's running economy,
      although the validity of this measure is often overlooked. PURPOSE: This study
      evaluated the validity of OC as a measure of running economy by comparison with
      the underlying energy cost (EC). In addition, the most appropriate method of
      removing the influence of body mass was determined to elucidate a measure of
      running economy that enables valid interindividual comparisons. METHODS: One
      hundred and seventy-two highly trained endurance runners (males, n = 101;
      females, n = 71) performed a discontinuous submaximal running assessment,
      consisting of approximately seven 3-min stages (1 km.h increments), to determine
      the absolute OC (L.km) and EC (kcal.km) for the four speeds below lactate turn
      point. RESULTS: Comparisons between models revealed linear ratio scaling to be a
      more suitable method than power function scaling for removing the influence of
      body mass for both EC (males, R = 0.589 vs 0.588; females, R = 0.498 vs 0.482)
      and OC (males, R = 0.657 vs 0.652; females, R = 0.532 vs 0.531). There were
      stepwise increases in EC and RER with increments in running speed (both, P <
      0.001). However, no differences were observed for OC across the four monitored
      speeds (P = 0.54). CONCLUSIONS: Although EC increased with running speed, OC was
      insensitive to changes in running speed and, therefore, does not appear to
      provide a valid index of the underlying EC of running, likely due to the
      inability of OC to account for variations in substrate use. Therefore, EC should
      be used as the primary measure of running economy, and for runners, an
      appropriate scaling with body mass is recommended.

PMID- 24561818
TI  - Validity of 24-h physical activity recall: physical activity measurement survey.
AB  - PURPOSE: The primary purpose of this study was to evaluate the validity of an
      interviewer-administered, 24-h physical activity recall (PAR) compared with that
      of the SenseWear Armband (SWA) for estimation of energy expenditure (EE) and
      moderate-to-vigorous physical activity (MVPA) in a representative sample of
      adults. A secondary goal was to compare measurement errors for various
      demographic subgroups (gender, age, and weight status). METHODS: A sample of 1347
      adults (20-71 yr, 786 females) wore an SWA for a single day and then completed a
      PAR, recalling the previous day's physical activity. The participants each
      performed two trials on two randomly selected days across a 2-yr time span. The
      EE and MVPA values for each participant were averaged across the 2 d. Group-level
      and individual-level agreement were evaluated using 95% equivalence testing and
      mean absolute percent error, respectively. Results were further examined for
      subgroups by gender, age, and body mass index. RESULTS: The PAR yielded
      equivalent estimates of EE (compared with those in the SWA) for almost all
      demographic subgroups, but none of the comparisons for MVPA were equivalent.
      Smaller mean absolute percent error values were observed for EE (ranges from
      10.3% to 15.0%) than those for MVPA (ranges from 68.6% to 269.5%) across all
      comparisons. The PAR yielded underestimates of MVPA for younger, less obese
      people but overestimates for older, more obese people. CONCLUSIONS: For EE
      measurement, the PAR demonstrated good agreement relative to the SWA. However,
      the use of PAR may result in biased estimates of MVPA both at the group and
      individual level in adults.

PMID- 24561820
TI  - Synthesis, molecular docking and cytotoxicity evaluation of novel 2-(4-amino
      benzosulfonyl)-5H-benzo[b]carbazole-6,11-dione derivatives as histone deacetylase
      (HDAC8) inhibitors.
AB  - A new series of 2-(4-aminobenzosulfonyl)-5H-benzo[b]carbazole-6,11-dione
      derivatives, which has not been reported yet, has been synthesized from 1,4
      naphthoquinone and 4-aminophenylsulfone involving an Michael addition,
      benzoylation and Pd catalyzed coupling. This set of compounds has been evaluated
      for in vitro cytotoxicity specifically against human cervical cancer cell line
      (SiHa) and most of the synthesized compounds exhibited good cytotoxic activity.
      Molecular docking of all the synthesized compounds was studied; among fourteen
      molecules docked compound 3 was the one with the best glide and E model score of 
      9.06 and -73.41, respectively which is close to the glide score of SAHA
      (standard). In all docked molecules, the compound 7a exhibits least glide and E
      model score of -2.97 and -71.02 respectively. 

PMID- 24561822
TI  - The perception of positive and negative facial expressions by unilateral stroke
      patients.
AB  - There remains conflict in the literature about the lateralisation of affective
      face perception. Some studies have reported a right hemisphere advantage
      irrespective of valence, whereas others have found a left hemisphere advantage
      for positive, and a right hemisphere advantage for negative, emotion. Differences
      in injury aetiology and chronicity, proportion of male participants, participant
      age, and the number of emotions used within a perception task may contribute to
      these contradictory findings. The present study therefore controlled and/or
      directly examined the influence of these possible moderators. Right brain-damaged
      (RBD; n=17), left brain-damaged (LBD; n=17), and healthy control (HC; n=34)
      participants completed two face perception tasks (identification and
      discrimination). No group differences in facial expression perception according
      to valence were found. Across emotions, the RBD group was less accurate thanthe
      HC group, however RBD and LBD group performancedid not differ. The lack of
      difference between RBD and LBD groups indicates that both hemispheres are
      involved in positive and negative expression perception. The inclusion of older
      adults and the well-defined chronicity range of the brain-damaged participants
      may have moderated these findings. Participant sex and general face perception
      ability did not influence performance. Furthermore, while the RBD group was less
      accurate than the LBD group when the identification task tested two emotions,
      performance of the two groups was indistinguishable when the number of emotions
      increased (four or six). This suggests that task demand moderates a study's
      ability to find hemispheric differences in the perception of facial emotion. 

PMID- 24561821
TI  - A retinoic acid-enhanced, multicellular human blood-brain barrier model derived
      from stem cell sources.
AB  - Blood-brain barrier (BBB) models are often used to investigate BBB function and
      screen brain-penetrating therapeutics, but it has been difficult to construct a
      human model that possesses an optimal BBB phenotype and is readily scalable. To
      address this challenge, we developed a human in vitro BBB model comprising brain
      microvascular endothelial cells (BMECs), pericytes, astrocytes and neurons
      derived from renewable cell sources. First, retinoic acid (RA) was used to
      substantially enhance BBB phenotypes in human pluripotent stem cell (hPSC)
      derived BMECs, particularly through adherens junction, tight junction, and
      multidrug resistance protein regulation. RA-treated hPSC-derived BMECs were
      subsequently co-cultured with primary human brain pericytes and human astrocytes
      and neurons derived from human neural progenitor cells (NPCs) to yield a fully
      human BBB model that possessed significant tightness as measured by
      transendothelial electrical resistance (~5,000 Omegaxcm(2)). Overall, this
      scalable human BBB model may enable a wide range of neuroscience studies. 

PMID- 24561824
TI  - Fluorescence correlation and lifetime correlation spectroscopy applied to the
      study of supported lipid bilayer models of the cell membrane.
AB  - Supported Lipid Bilayers (SLBs) are versatile models capable of mimicking some of
      the key properties of the cell membrane, including for example lipid fluidity,
      domain formation and protein support, without the challenging complexity of the
      real biological system. This is important both from the perspective of
      understanding the behaviour and role of the lipid membrane in cell structure and
      signalling, as well as in development of applications of lipid membranes across
      domains as diverse as sensing and drug delivery. Lipid and protein diffusion
      within the membrane is vital to its function and there are several key
      experimental methods used to study membrane dynamics. Amongst the optical methods
      are Fluorescence Recovery After Photobleaching (FRAP), single particle tracking
      and Fluorescence Correlation (and Fluorescence Lifetime Correlation) Spectroscopy
      (FCS/FLCS). Each of these methods can provide different and often complementary
      perspectives on the dynamics of the fluid membrane. Although FCS is well
      established, FLCS is a relatively new technique and both methods have undergone a
      number of extensions in recent years which improve their precision and accuracy
      in studying supported lipid bilayers, most notably z-scan methods. This short
      review focusses on FCS and FLCS and their recent applications, specifically to
      artificial lipid bilayer studies addressing key issues of cell membrane
      behaviour. 

PMID- 24561825
TI  - Deciphering early development of complex diseases by progressive module network.
AB  - There is no effective cure nowadays for many complex diseases, and thus it is
      crucial to detect and further treat diseases in earlier stages. Generally, the
      development and progression of complex diseases include three stages: normal
      stage, pre-disease stage, and disease stage. For diagnosis and treatment, it is
      necessary to reveal dynamical organizations of molecular modules during the early
      development of the disease from the pre-disease stage to the disease stage. Thus,
      we develop a new framework, i.e. we identify the modules presenting at the pre
      disease stage (pre-disease module) based on dynamical network biomarkers (DNBs),
      detect the modules observed at the advanced stage (disease-responsive module) by
      cross-tissue gene expression analysis, and finally find the modules related to
      early development (progressive module) by progressive module network (PMN). As an
      application example, we used this new method to analyze the gene expression data
      for NOD mouse model of Type 1 diabetes mellitus (T1DM). After the comprehensive
      comparison with the previously reported milestone molecules, we found by PMN: (1)
      the critical transition point was identified and confirmed by the tissue-specific
      modules or DNBs relevant to the pre-disease stage, which is considered as an
      earlier event during disease development and progression; (2) several key tissues
      common modules related to the disease stage were significantly enriched on known
      T1DM associated genes with the rewired association networks, which are marks of
      later events during T1DM development and progression; (3) the tissue-specific
      modules associated with early development revealed several common essential
      progressive genes, and a few of pathways representing the effect of environmental
      factors during the early T1DM development. Totally, we developed a new method to
      detect the critical stage and the key modules during the disease occurrence and
      progression, and show that the pre-disease modules can serve as warning signals
      for the pre-disease state (e.g. T1DM early diagnosis) whereas the progressive
      modules can be used as the therapy targets for the disease state (e.g. advanced
      T1DM), which were also validated by experimental data. 

PMID- 24561826
TI  - Construction and characterization of adenoviral vectors for the delivery of
      TALENs into human cells.
AB  - Transcription activator-like effector nucleases (TALENs) are designed to cut the
      genomic DNA at specific chromosomal positions. The resulting DNA double strand
      break activates cellular repair pathways that can be harnessed for targeted
      genome modifications. TALENs thus constitute a powerful tool to interrogate the
      function of DNA sequences within complex genomes. Moreover, their high DNA
      cleavage activity combined with a low cytotoxicity make them excellent candidates
      for applications in human gene therapy. Full exploitation of these large and
      repeat-bearing nucleases in human cell types will benefit largely from using the
      adenoviral vector (AdV) technology. The genetic stability and the episomal nature
      of AdV genomes in conjunction with the availability of a large number of AdV
      serotypes able to transduce various human cell types make it possible to achieve
      high-level and transient expression of TALENs in numerous target cells,
      regardless of their mitotic state. Here, we describe a set of protocols detailing
      the rescue, propagation and purification of TALEN-encoding AdVs. Moreover, we
      describe procedures for the characterization and quantification of recombinant
      viral DNA present in the resulting AdV preparations. The protocols are preceded
      by information about their underlying principles and applied in the context of
      second-generation capsid-modified AdVs expressing TALENs targeted to the AAVS1
      "safe harbor" locus on human chromosome 19.

PMID- 24561828
TI  - In situ enrichment of folate by microorganisms in beta-glucan rich oat and barley
      matrices.
AB  - The objective was to study folate production of yeast strains, bacteria isolated
      from oat bran, and selected lactic acid bacteria as well as one propionibacterium
      in oat and barley based models. Simultaneously, we aimed at sustaining the
      stability of viscosity, representing the physicochemical state of beta-glucan.
      Total folate contents were determined microbiologically and vitamers for selected
      samples by UHPLC. Folate in yeast cells comprised mainly 5-methyltetrahydrofolate
      and tetrahydrofolate. Folate production by microbes in YPD medium was different
      to that in cereal fermentations where vitamers included 5-methyltetrahydrofolate,
      5,10-methenyltetrahydrofolate and formylated derivatives. Microbes producing
      significant amounts of folate without affecting viscosity were Saccharomyces
      cerevisiae ALKO743 and Candida milleri ABM4949 among yeasts and Pseudomonas sp.
      ON8 and Janthinobacterium sp. RB4 among bacteria. Net folate production was up to
      120 ng/g after 24 h fermentation and could increase during 2-week storage.
      Glucose addition increased the proportion of 5-methyltetrahydrofolate.
      Streptococcus thermophilus ABM5097, Lactobacillus reuteri, and Propionibacterium
      sp. ABM5378 produced folate but in lower concentrations. Both endogenous and
      added microbes contribute to folate enhancement. Selection of microbes with
      folate producing capability and limited hydrolytic activity will enable the
      development of products rich in folate and beta-glucan.

PMID- 24561827
TI  - Tissue fixation and the effect of molecular fixatives on downstream staining
      procedures.
AB  - It is impossible to underplay the importance of fixation in histopathology.
      Whether the scientist is interested in the extraction of information on lipids,
      proteins, RNA or DNA, fixation is critical to this extraction. This review aims
      to give a brief overview of the current "state of play" in fixation and focus on
      the effect fixation, and particularly the effect of the newer brand of "molecular
      fixatives" have on morphology, histochemistry, immunohistochemistry and RNA/DNA
      analysis. A methodology incorporating the creation of a fixation tissue
      microarray for the study of the effect of fixation on histochemistry is detailed.

PMID- 24561830
TI  - ISWI chromatin remodeling: one primary actor or a coordinated effort?
AB  - The ISWI family of ATP-dependent chromatin remodelers regulates transcription of
      coding and noncoding RNA by mobilizing nucleosomes and controlling the length of
      linker DNA separating nucleosomes (spacing). Nucleosome movement is tightly
      coupled to the DNA translocation activity of the helicase domain in the catalytic
      subunit. There may be other domains besides the helicase domain needed to move
      DNA in and out of nucleosomes. The C terminus of the ISWI catalytic subunit with
      the conserved HAND, SANT, and SLIDE domains may be involved in nucleosome
      spacing. There are several models of how the C terminus may facilitate in ISWI
      remodeling such as regulating the activity of the helicase domain and causing the
      helicase domain to translocate more efficiently on DNA or to enhance its
      selectivity for nucleosomes. Another possibility is that domains like SLIDE
      promote linker DNA entering into nucleosomes in a coordinated manner with the
      helicase domain. 

PMID- 24561831
TI  - High-throughput SNP discovery and transcriptome expression profiles from the
      salmon louse Caligus rogercresseyi (Copepoda: Caligidae).
AB  - The salmon louse Caligus rogercresseyi is the dominant ectoparasite species
      affecting the salmon aquaculture industry in the Southern hemisphere, and it is
      currently the main cause for economic losses in Chilean aquaculture. However,
      despite the great concern over Caligus infestations, genomic information on this
      louse is still scarce, even while the need to develop high-resolution molecular
      markers is growing. This study provides the first deep transcriptome survey to
      identify thousands of SNP markers from C. rogercresseyi, with a total of 69,466
      SNPs identified using the MiSeq platform (Illumina(r)), 30,605 (52%) of which
      were found in contigs successfully annotated against known protein databases.
      Furthermore, in silico gene expression profiles associated with SNP variants were
      evaluated, and the results evidenced a wide array of genes that were down- and
      upregulated throughout the developmental stages of C. rogercresseyi.
      Interestingly, putative KEGG pathways involved in resistance to antiparasitic
      agents were also identified, where ten pathways were associated with the nervous
      system and one was related to ABC transporters. Taken together, this information
      could be highly useful for investigating the molecular underpinnings involved in
      the susceptibility or resistance of salmon lice to chemical treatments. 

PMID- 24561833
TI  - [The role of kidney transplantation in reducing mortality in a chronic dialysis
      program].
AB  - For patients with chronic renal failure (CRF), kidney transplant (KT) is a better
      alternative to dialysis in terms of survival, life quality and costs. We studied
      the general characteristics, causes and survival rate of the dialysis population
      in 2010. We evaluated broader criteria for acceptance of transplants has affected
      the results of the procedure in that period. A total of 118 dialysis patients
      were included; mean age 56.9 +/- 18.4 years, dialysis duration 45.5 +/- 59.6
      months, main cause of CRF was diabetes in 35 (30%), and 58 (49%) were included in
      waiting list for KT. Of the 34 patients who finished dialysis in 2010, 18 (53%)
      were KT, while 12 (35%) died (cardiovascular 50%, infectious 17%). Survival at 12
      months was 85% for the total group, 98% on waiting list and 72% those who were
      not enrolled. During 2010 there were 88 KT, 62 with cadaveric donors (CD), 18
      with living donors and 8 with double pancreas-kidney transplants. Recipients of
      CD were 50.7 years old, with 67 months on dialysis, 8 (13%) diabetics, and 12
      (20%) with previous KT. Donors had a mean age of 45 years, 28 (45%) expanded
      criteria, and 27.7 hours of cold ischemia time. During an approximate follow-up
      of 11.4 months, 13 (21%) suffered acute graft rejection, survival was 88% for
      graft and 93% for patients. We emphasize KT as the main cause of success as
      regards dialysis. No differences in risk factors were found to significantly
      affect graft or patient survival. 

PMID- 24561834
TI  - [Treatment of pulmonary tuberculosis in a low-prevalence urban area. Compliance
      and sputum conversion].
AB  - Several factors could be responsible for a delay in bacteriological conversion of
      sputum in patients with pulmonary tuberculosis (pTB) even under proper treatment.
      We aimed to determine those factors associated with follow-up test compliance and
      bacteriologic conversion at month two of treatment in patients with pTB who were
      receiving directly controlled treatment (DOT) in an urban area with low TB burden
      (notification rate: 14.9 cases/100 000, 2010-2011). We retrospectively analyzed
      the clinical, demographic, radiological, microbiological and therapeutic
      characteristics of 196 new smear-positive pTB cases. The proportion of patients
      who underwent bacteriological examination was 79.1% (155/196) and 74.7% (121/162)
      at the second and last month of treatment. Smear examinations were significantly
      more frequent in patients with co-morbidities or receiving DOT in health
      facilities with laboratory access. Diabetes (OR 17.4, 95% CI 2.0 - 27.0) and high
      smear grade (OR 13.8, 95% CI 1.8 - 108.0) were highly associated with persistent
      positive smears. Cavitation (OR 4.6, 95%, CI 1.1 - 20.5) and diabetes (OR 3.3,
      95% CI 1.1 - 10.5) were associated with persistent positive cultures. Smear
      examination results at two months of treatment indicated a sensitivity of 63.9%
      (23/36) and a specificity of 82.4% (98/119) in relation to culture. The limited
      predictive value of smear examination relative to culture results indicated the
      need to find other markers for sputum conversion. Identification of risk factors
      associated with persistent sputum positivity could contribute to patient care and
      resource allocation. Prolonged infectiousness in patients with diabetes could
      indicate the need to review TB control strategies. 

PMID- 24561832
TI  - Post-fusion structural changes and their roles in exocytosis and endocytosis of
      dense-core vesicles.
AB  - Vesicle fusion with the plasma membrane generates an Omega-shaped membrane
      profile. Its pore is thought to dilate until flattening (full-collapse), followed
      by classical endocytosis to retrieve vesicles. Alternatively, the pore may close
      (kiss-and-run), but the triggering mechanisms and its endocytic roles remain
      poorly understood. Here, using confocal and stimulated emission depletion
      microscopy imaging of dense-core vesicles, we find that fusion-generated Omega
      profiles may enlarge or shrink while maintaining vesicular membrane proteins.
      Closure of fusion-generated Omega-profiles, which produces various sizes of
      vesicles, is the dominant mechanism mediating rapid and slow endocytosis within
      ~1-30 s. Strong calcium influx triggers dynamin-mediated closure. Weak calcium
      influx does not promote closure, but facilitates the merging of Omega-profiles
      with the plasma membrane via shrinking rather than full-collapse. These results
      establish a model, termed Omega-exo-endocytosis, in which the fusion-generated
      Omega-profile may shrink to merge with the plasma membrane, change in size or
      change in size then close in response to calcium, which is the main mechanism to
      retrieve dense-core vesicles.

PMID- 24561835
TI  - [Healthcare associated pneumonia].
AB  - Healthcare associated pneumonia (HCAP) is a different entity from community
      acquired pneumonia and nosocomial pneumonia. There exist several risk factors
      that lead to it. Different features, severity and pathogens are described and
      there is controversy about the initial empirical treatment. The aim of this work
      was to analyze the etiology, clinical characteristics and evolution of the HCAP.
      It is a prospective and observational study that includes 60 patients; 32 had
      previous hospitalization during the last 90 days, 9 were under hemodialysis, 12
      residents in nursing homes and 7 received outpatient intravenous therapy. The
      mean age was 63 years and the severity index was high. The most frequent
      comorbidities were cardiac. The radiological compromise was more than one lobe in
      42% of cases and 18% had pleural effusion. Germ isolation was obtained in 30% of
      patients where the most isolated germ was Streptococcus pneumoniae (9 cases).
      There was only one case of multidrug-resistance. The mean length hospital stay
      was 11 days, six patients had complications and mortality was 5%. Complications
      but not mortality were significantly higher in the group of patients on
      hemodialysis (p value = 0.011 and 0.056 respectively). The antibiotic-resistance
      found do not justify a change in the antibiotic treatment commonly used for
      community acquired pneumonia. 

PMID- 24561836
TI  - Milk improved the metabolic syndrome in obese beta rats.
AB  - The response of adult spontaneously obese rats from the IIMb/Beta strain fed a
      high calcium skimmed milk diet (MHCa), high calcium from carbonate (HCa) and a
      normal AIN 93 diet during 45 days was evaluated. Body weight, food intake and
      fecal fat excretion were measured. At the end of the experiment rats were
      euthanized, abdominal fat pads and livers were excised and weighed. Blood and
      liver triacylglycerols, total cholesterol and fractions were quantified. Body
      weight increase and abdominal fat pads in the MHCa group were significantly lower
      than in the other two. Plasma triacylglycerols, total and LDL-cholesterol were
      diminished in the MHCa group. Fecal lipid excretion was increased in the adult
      MHCa group. Total liver lipids and triacylglycerols showed a significant
      diminution in the MHCa group. These results suggest that calcium and other
      bioactive compounds from milk, most probably present in whey fraction, and not
      calcium carbonate exerted an "anti-obesity" effect on these rats.

PMID- 24561837
TI  - [Soil transmitted helminthiasis in Argentina. A systematic review].
AB  - A systematic review of surveys performed between 1980 and 2011 (published in
      MEDLINE/Pubmed and/or LILACS indexed journals, available in the baseline data
      from a Mass Deworming National Program (MDNP, 2005) was used to identify the
      prevalence, distribution and detection of risk areas for soil transmitted
      helminth infections (STH) in Argentina. We found 310 publications in the database
      using the pre-defined key-words (medical subject headings) for research purposes.
      Only 24 articles with 26 surveillance sites in 8 provinces and a total of 5495
      surveyed individuals fulfilled the inclusion criteria. Frequency rates for STH
      had a wide range: Ascaris lumbricoides: 0-67%, hookworms: 0-90%, Trichuris
      trichiura: 0-24.6 and Strongyloides stercoralis: 0-83%. The estimated combined
      incidence varied from 0.8% to 88.6%. Baseline surveys from the MDNP reporting on
      1943 children from 12 provinces confirmed the heterogeneity, with combined STH
      frequency rates ranging from 0 to 42.7%. Surveys included in this review showed
      that the distribution of STH in Argentina is not homogeneous, with areas of high
      incidence (> 20%) in the northeastern and northwestern provinces where mass
      deworming activities would be highly beneficial. In several surveys, the high
      overall incidence was mostly due to hookworms and S. stercoralis, a situation to
      be considered when selecting diagnostic and therapeutic control strategies. The
      scarcity or absence of data from various provinces and the availability of less
      than 8000 surveyed individuals should be considered. 

PMID- 24561838
TI  - [Moderate control of hyperglycemia after acute stroke in the intensive care
      unit].
AB  - Hyperglycemia following an ischemic stroke has been associated with poor clinical
      outcome. We retrospectively assessed the effect of moderately controlled plasma
      glucose (correction from 135mg/dl) compared to conservative treatment (correction
      from 200 mg/dl), as regards neurological evolution, duration of hospitalization,
      at discharge and at 30 days post-discharge, also complications associated with
      the treatment in patients admitted to the intensive care unit. We studied 208
      patients, 103 (24% diabetics) with moderate therapy and 105 (23% diabetics) with
      conservative treatment. The average blood glucose during hospitalization tended
      to be lower with the moderate treatment with no statistic significance (129 +/-
      30 vs. 138 +/- 31 mg/dl; p = 0.06). The difference was significant in non
      diabetics (119 +/- 24 vs. 128 +/- 24 mg/dl; p < 0.05), being even more pronounced
      in those non-diabetics with moderate to severe neurological deficit on admission
      (116 +/- 23 vs. 130 +/- 23 mg/dl; p < 0.01). Patients admitted with moderate to
      severe neurological deficit and treated with moderate regime had a better outcome
      at discharge and at 30 days (NIHSS variation: high 2.1 +/- 2.6 vs. 3.4 +/- 3; 30
      days: 3.2 +/- 3 vs. 4.8 +/- 3; p < 0.01). The duration of hospitalization was
      lower in the moderate treatment group (5.7 vs. 9.2 days, p < 0.05), with no
      significant difference showing in the incidence of hypoglycemia in either group.
      In conclusion, moderate control of blood glucose in ACVi patients relates to an
      improved neurological outcome in those admitted with moderate to severe
      neurological deficits (NIH scale = 4), with a reduced hospital stay, and no
      substantial increase of hypoglycemia episodes. 

PMID- 24561840
TI  - [Symptomatic giant arachnoid cyst].

PMID- 24561841
TI  - [Vacuum sign of cerebrospinal fluid flow].

PMID- 24561839
TI  - [Takotsubo Syndrome: experience in three institutions of Cordoba City].
AB  - Takotsubo Syndrome is an acquired cardiomyopathy characterized by a transient
      left ventricular antero-apical asynergy or disynergy (apical ballooning),
      symptoms and electrocardiographic changes are suggestive of an acute coronary
      syndrome, moderate cardiac enzymatic release and absence of significant
      atherosclerotic lesions in coronary arteries. It predominantly affects
      postmenopausal women and it is frequently preceded by situations of physical or
      psychological stress. The physiopathology is not completely understood but there
      is consensus that it is triggered by a surge of catecholamines consequent to the
      aforementioned stress conditions. The study of 32 cases diagnosed at three
      medical institutions in Cordoba, Argentina, is reported. The mean age was 61
      years, and 28 were female. All cases simulated acute coronary syndromes.
      Congestive heart failure developed in twelve cases (37.5%) and two patients
      (6.3%) developed cardiogenic shock. The left ventricular function normalized more
      rapidly than the electrocardiographic changes. The recurrence rate was 25%, the
      prognosis was benign considering that only one death occurred following a
      relapse. In general the findings are similar to previously published studies.
      Recent advances in the comprehension of the physiopathology of this
      cardiomyopathy gave way to the development of a rational therapeutic approach. 

PMID- 24561842
TI  - [Use of plasmapheresis in hypertriglyceridemic pancreatitis].
AB  - Hypertriglyceridemia is reported as cause of 1 to 4% of the episodes of acute
      pancreatitis. We report the case of a 42-year-old woman with a history of
      obesity, type 2 diabetes mellitus, hypertriglyceridemia and hypercholesterolemia,
      with triglycerides of 9365 mg/dl, total cholesterol of 1822 mg/dl, one month
      prior to the consultation. She presented at the emergency unit with a 5 day
      history of abdominal pain, which progressed in intensity in the last 48 hours.
      Abdominal computed tomography revealed pancreatic and peripancreatic
      inflammation. Thirty-six hours after admission, a first session of plasmapheresis
      was conducted with a plasma triglyceride and cholesterol reduction of 25 and 30%,
      respectively. A second session was performed the next day, with a further
      reduction of triglycerides to 996 mg/dl and cholesterol to 238 mg/dl. During
      hospitalization the patient presented fever and Klebsiella pneumoniae bacteremia
      with no pancreatic collection or necrosis in tomography and, later on, nosocomial
      pneumonia, both infections with adequate response to antibiotic therapy. At the
      time of discharge, triglycerides and cholesterol levels were 652 mg/dl and 167
      mg/dl respectively, no abdominal pain was present and the patient resumed oral
      nutrition. We observed a 90% reduction of triglycerides and 87% of cholesterol
      after 2 sessions of plasmapheresis, compared to 70% in average of reduction in
      most of the studies reviewed. We did not find the presence of bacteremia or
      nosocomial pneumonia as complications in the reported cases. 

PMID- 24561843
TI  - [Hiccup, a diagnostic challenge].
AB  - Hiccup is a spasmodic involuntary contraction of the diaphragm which triggers a
      sudden inspiration and an abrupt closure of the glottis with a characteristic
      sound. Regarding its duration, it is classified as hiccup attack, persistent
      hiccup or rebellious or intractable hiccup. We present the case of a 75 old male
      with rebellious hiccup which prevented him to fall asleep by day or by night,
      associated with belches lasting for three years, refractory to chlorpromazine. An
      extensive evaluation led to the diagnosis of right ethmoid sinus tumor. The tumor
      resection was performed and after subsequent local radiotherapy the hiccup
      disappeared. We consider this a rare cause of rebellious hiccup that generated a
      diagnostic and therapeutic challenge. 

PMID- 24561844
TI  - [Febrile cholestatic jaundice as an initial manifestation of Hodgkin's disease].
AB  - The febrile cholestatic disease as a presentation of Hodgkin's lymphoma is a very
      unusual condition. We describe here the case of a patient with prolonged fever of
      unknown origin and progressive jaundice, in whom the diagnosis was made with the
      analysis of a liver biopsy, given the absence of lymph node involvement that
      characterizes this disease. We remark the severe and multisystemic involvement of
      this rapidly progressive disease. 

PMID- 24561845
TI  - [Chylopericardium and bilateral chylothorax in a breast cancer patient].
AB  - Non traumatic chylopericar dium is mostly secondary to infection, congenital or
      neoplastic disease that invade mediastinal lymph nodes and modify the normal
      lymphatic flow. It is associated to chylothorax in approximately 3% of cases. We
      report the case of a 52 years old woman with diagnosis of advanced breast cancer.
      She was admitted with bilateral pleural effusion and echocardiographic signs of
      cardiac tamponade. A CT scan disclosed multiple mediastinal lymphadenopathy. The
      level of tryglicerides in pleural effusion was 372 mg/dl. A percutaneous
      pericardiocentesis was performed, obtaining chyle, with 984 mg/dl of
      tryglicerides and cholesterol 90 mg/dl levels. Treatment strategy was modified.
      We reviewed pathophysiology, diagnostic criteria and treatment of this rare
      entity. 

PMID- 24561846
TI  - [Update on the diagnosis of diabetes].
AB  - Diabetes mellitus is a chronic metabolic disease characterized by the presence of
      hyperglycemia. This condition must be detected early in order to establish a
      proper treatment and prevent its micro and macro vascular complications. The
      diagnosis of diabetes mellitus is based on the detection of abnormally high
      levels of glycemia. This task may appear to be simple but should not be
      underestimated. Misclassifying an individual as a diabetic can expose him/her not
      only to emotional damage but also to unnecessary diagnostic tests and potentially
      harmful treatments. Many different clinical situations such as pregnancy or acute
      critical illness may hamper the interpretation of laboratory findings. In this
      article, we present an updated review on the main aspects related to diagnosis of
      diabetes mellitus. 

PMID- 24561847
TI  - [Telomerase and telomere: their structure and dynamics in health and disease].
AB  - Telomerase is the enzyme responsible for the maintenance of telomere length by
      adding guanine-rich repetitive sequences. Its activity can be seen in gametes,
      stem cells and tumor cells. In human somatic cells the proliferative potential is
      limited, reaching senescence after 50-70 cell divisions, because the DNA
      polymerase is not able to copy the DNA at the ends of chromosomes. By contrast,
      in most tumor cells the replicative potential is unlimited due to the maintenance
      of the telomeric length given by telomerase. Telomeres have additional proteins
      that regulate the binding of telomerase, likewise telomerase associates, with a
      protein complex that regulates its activity. This work focuses on the structure
      and function of the telomere/telomerase complex and how changes in its behavior
      lead to the development of different diseases, mainly cancer. Development of
      inhibitors of the telomere/telomerase complex could be a target with promising
      possibilities. 

PMID- 24561848
TI  - [Filippo Pacini and cholera, 1854].

PMID- 24561849
TI  - [Seven decades in biomedical research (1942-2013)].

PMID- 24561850
TI  - [On quaternary prevention and defensive medicine].

PMID- 24561851
TI  - [Quaternary prevention and Knock and Ulysses syndromes].

PMID- 24561852
TI  - [Quaternary prevention and essential prevention].

PMID- 24561853
TI  - [Quaternary prevention and the contribution of critical reading of the literature
      in medicine].

PMID- 24561854
TI  - [Hospital pharmacovigilance in Buenos Aires].

PMID- 24561855
TI  - [Is there a difference in basic research between animal and human medicine?].

PMID- 24561856
TI  - [Concerning an article on the relation between mortality and the day of surgery,
      commented on Caveat lector].

PMID- 24561857
TI  - [Plantar vein thrombosis as a cause of local pain].

PMID- 24561858
TI  - The American Journal of Physiology-Heart and Circulatory Physiology: a long
      history, a bright future.

PMID- 24561859
TI  - Cardiac electrophysiology and the susceptibility to sustained ventricular
      tachycardia in intact, conscious mice.
AB  - Cardiac electrophysiological dysfunction is a major cause of death in humans.
      Accordingly, electrophysiological testing is routinely performed in intact,
      conscious, humans to evaluate arrhythmias and disorders of cardiac conduction.
      However, to date, in vivo electrophysiological studies in mice are limited to
      anesthetized open-chest or closed-chest preparations. However, cardiac
      electrophysiology in anesthetized mice or mice with surgical trauma may not
      adequately represent what occurs in conscious mice. Accordingly, an intact,
      conscious murine model of cardiac electrophysiology has the potential to be of
      major importance for advancing the concepts and methods that drive cardiovascular
      therapies. Therefore, we describe, for the first time, the use of an intact,
      conscious, murine model of cardiac electrophysiology. The conscious mouse model
      permits measurements of atrioventricular interval, sinus cycle length, sinus node
      recovery time (SNRT), SNRT corrected for spontaneous sinus cycle, Wenckebach
      cycle length, the ventricular effective refractory period (VERP) and the
      electrical stimulation threshold to induce sustained ventricular tachyarrhythmias
      in an intact, complex model free of the confounding influences of anesthetics and
      surgical trauma. This is an important consideration because anesthesia and
      surgical trauma markedly reduced cardiac output and heart rate as well as altered
      cardiac electrophysiology parameters. Most importantly, anesthesia and surgical
      trauma significantly increased the VERP and virtually eliminated the ability to
      induce sustained ventricular tachyarrhythmias. Accordingly, the methodology
      allows for the accurate documentation of cardiac electrophysiology in complex,
      conscious mice and may be adopted for advancing the concepts and ideas that drive
      cardiovascular research.

PMID- 24561860
TI  - Cardiomyocyte glycophagy is regulated by insulin and exposure to high
      extracellular glucose.
AB  - Disturbed systemic glycemic and insulinemic status elicits cardiomyocyte
      metabolic stress and altered glucose handling. In diabetes, pathological
      myocardial glycogen accumulation occurs. Recently, evidence of a specific
      myocardial autophagic degradation pathway for glycogen ("glycophagy") has been
      reported, differentiated from the more well-characterized protein "macrophagy"
      pathway. The goal of this study was to identify potential mechanisms involved in
      cardiac glycogen accumulation, glycophagy, and macrophagy regulation using
      cultured neonatal rat ventricular myocytes (NRVMs). In NRVMs, insulin-induced Akt
      phosphorylation was evident with 5 mM-glucose conditions (~2.3-fold increased).
      Under high-glucose (30 mM) conditions, insulin-augmented phosphorylation was not
      observed. Accumulation of glycogen was observed in response to insulin only in
      high-glucose conditions (~2-fold increase). Increased expression of the
      glycophagy marker starch-binding domain-containing protein-1 (STBD1, 25%
      increase) was observed under high-glucose and insulin conditions. Expression
      levels of the macrophagy markers p62 and light chain protein 3BII:I were not
      increased by insulin at either glucose level. Preliminary results from hearts of
      streptozotocin-treated diabetic rats are supportive of the findings obtained in
      NRVMs, suggesting diabetes induced elevated expression of STBD1 and of an
      additional glycophagy marker GABA(A) receptor-associated protein-like 1. Confocal
      microscopy demonstrated that light chain protein 3B and STBD1 immunomarkers were
      not colocalized in NRVMs. These findings provide the first evidence that
      cardiomyocyte glycophagy induction occurs under the influence of insulin and is
      responsive to extracellular high glucose. This study suggests that the regulation
      of glycogen content and glycophagy induction in the cardiomyocyte may be linked,
      and it is speculated that glycogen pathology in diabetic cardiomyopathy has
      glycophagic involvement.

PMID- 24561861
TI  - Adaptive right ventricular performance in response to acutely increased afterload
      in a lamb model of congenital heart disease: evidence for enhanced Anrep effect.
AB  - Patients with pulmonary hypertension associated with congenital heart disease
      survive longer with preserved right ventricular (RV) function compared with those
      with primary pulmonary hypertension. The purpose of this study was to test the
      hypothesis that superior RV performance can be demonstrated, at baseline and when
      challenged with increased RV afterload, in lambs with chronic left-to-right
      cardiac shunts compared with control lambs. A shunt was placed between the
      pulmonary artery and the aorta in fetal lambs (shunt). RV pressure-volume loops
      were obtained 4 wk after delivery in shunt and control lambs, before and after
      increased afterload was applied using pulmonary artery banding (PAB). Baseline
      stroke volume (8.7 +/- 1.8 vs. 15.8 +/- 2.7 ml, P = 0.04) and cardiac index (73.0
      +/- 4.0 vs. 159.2 +/- 25.1 ml.min(-1).kg(-1), P = 0.02) were greater in shunts.
      After PAB, there was no difference in the change in cardiac index (relative to
      baseline) between groups; however, heart rate (HR) was greater in controls (168
      +/- 7.3 vs. 138 +/- 6.6 beats/min, P = 0.01), and end-systolic elastance (Ees)
      was greater in shunts (2.63 vs. 1.31 * baseline, P = 0.02). Control lambs showed
      decreased mechanical efficiency (71% baseline) compared with shunts. With acute
      afterload challenge, both controls and shunts maintained cardiac output; however,
      this was via maladaptive responses in controls, while shunts maintained
      mechanical efficiency and increased contractility via a proposed enhanced Anrep
      effect-the second, slow inotropic response in the biphasic ventricular response
      to increased afterload, a novel finding in the RV. The mechanisms related to
      these physiological differences may have important therapeutic implications.

PMID- 24561862
TI  - Inhibition of endocytosis exacerbates TNF-alpha-induced endothelial dysfunction
      via enhanced JNK and p38 activation.
AB  - Tumor necrosis factor-alpha (TNF-alpha) is a pro-inflammatory cytokine that
      causes endothelial dysfunction. Endocytosis of TNF-alpha receptors (TNFR)
      precedes endosomal reactive oxygen species (ROS) production, which is required
      for NF-kappaB activation in vascular smooth muscle cells. It is unknown how
      endocytosis of TNFRs impacts signaling in endothelial cells. We hypothesized that
      TNF-alpha-induced endothelial dysfunction is induced by both endosomal and cell
      surface events, including NF-kappaB and mitogen-activated protein kinases (MAPKs)
      activation, and endocytosis of the TNFR modifies signaling. Mesenteric artery
      segments from C57BL/6 mice were treated with TNF-alpha (10 ng/ml) for 22 h in
      tissue culture, with or without signaling inhibitors (dynasore for endocytosis,
      SP600125 for JNK, SB203580 for p38, U0126 for ERK), and vascular function was
      assessed. Endothelium-dependent relaxation to acetylcholine (ACh) was impaired by
      TNF-alpha, and dynasore exacerbated this, whereas JNK or p38 inhibition prevented
      these effects. In cultured endothelial cells from murine mesenteric arteries,
      dynasore potentiated JNK and p38 but not ERK phosphorylation and promoted cell
      death. NF-kappaB activation by TNF-alpha was decreased by dynasore. JNK
      inhibition dramatically increased both the magnitude and duration of TNF-alpha
      induced NF-kappaB activation and potentiated intercellular adhesion molecule-1
      (ICAM-1) activation. Dynasore still inhibited NF-kappaB activation in the
      presence of SP600125. Thus TNF-alpha-induced endothelial dysfunction is both JNK
      and p38 dependent. Endocytosis modulates the balance of NF-kappaB and MAPK
      signaling, and inhibition of NF-kappaB activation by JNK limits this pro
      proliferative signal, which may contribute to endothelial cell death in response
      to TNF-alpha.

PMID- 24561864
TI  - Downregulation of L-type Ca2+ channel in rat mesenteric arteries leads to loss of
      smooth muscle contractile phenotype and inward hypertrophic remodeling.
AB  - L-type Ca(2+) channels (LTCCs) are important for vascular smooth muscle cell
      (VSMC) contraction, as well as VSMC differentiation, as indicated by loss of
      LTCCs during VSMC dedifferentiation. However, it is not clear whether loss of
      LTCCs is a primary event underlying phenotypic modulation or whether loss of
      LTCCs has significance for vascular structure. We used small interference RNA
      (siRNA) transfection in vivo to investigate the role of LTCCs in VSMC phenotypic
      expression and structure of rat mesenteric arteries. siRNA reduced LTCC mRNA and
      protein expression in rat mesenteric arteries 3 days after siRNA transfection to
      12.7 +/- 0.7% and 47.3 +/- 13%, respectively: this was associated with an
      increased resting intracellular Ca(2+) concentration ([Ca(2+)]i). Despite the
      high [Ca(2+)]i, the contractility was reduced (tension development to
      norepinephrine was 3.5 +/- 0.2 N/m and 0.8 +/- 0.2 N/m for sham-transfected and
      downregulated arteries respectively; P < 0.05). Expression of contractile
      phenotype marker genes was reduced in arteries downregulated for LTCCs.
      Phenotypic changes were associated with a 45% increase in number of VSMCs and a
      consequent increase of media thickness and media area. Ten days after siRNA
      transfection arterial structure was again normalized. The contractile responses
      of LTCC-siRNA transfected arteries were elevated in comparison with matched
      controls 10 days after transfection. The study provides strong evidence for
      causal relationships between LTCC expression and VSMC contractile phenotype, as
      well as novel data addressing the complex relationship between VSMC
      contractility, phenotype, and vascular structure. These findings are relevant for
      understanding diseases, associated with phenotype changes of VSMC and vascular
      remodeling, such as atherosclerosis and hypertension. 

PMID- 24561863
TI  - Soluble epoxide hydrolase-dependent regulation of myogenic response and blood
      pressure.
AB  - Epoxyeicosatrienoic acids (EETs) are metabolites of arachidonic acid via
      cytochrome P450 (CYP)/epoxygenases. EETs possess cardioprotective properties and
      are catalyzed by soluble epoxide hydrolase (sEH) to dihydroxyeicosatrienoic acids
      (DHETs) that lack vasoactive property. To date, the role of sEH in the regulation
      of myogenic response of resistant arteries, a key player in the control of blood
      pressure, remains unknown. To this end, experiments were conducted on sEH
      knockout (KO) mice, wild-type (WT) mice, and endothelial nitric oxide synthase
      (eNOS)-KO mice treated with t-TUCB, a sEH inhibitor, for 4 wk. sEH-KO and t-TUCB
      treated mice displayed significantly lower blood pressure, associated with
      significantly increased vascular EETs and ratio of EETs/DHETs. Pressure-diameter
      relationships were assessed in isolated and cannulated gracilis muscle
      arterioles. All arterioles constricted in response to increases in transmural
      pressure from 60 to 140 mmHg. The myogenic constriction was significantly
      reduced, expressed as an upward shift of pressure-diameter curve, in arterioles
      of sEH-KO and t-TUCB-treated eNOS-KO mice compared with their controls. Removal
      of the endothelium, or treatment of the vessels with PPOH, an inhibitor of EET
      synthase, restored the attenuated pressure-induced constriction to the levels
      similar to those observed in their controls but had no effects on control
      vessels. No difference was observed in the myogenic index, or in the vascular
      expression of eNOS, CYP2C29 (EET synthase), and CYP4A (20-HETE synthase) among
      these groups of mice. In conclusion, the increased EET bioavailability, as a
      function of deficiency/inhibition of sEH, potentiates vasodilator responses that
      counteract pressure-induced vasoconstriction to lower blood pressure.

PMID- 24561865
TI  - Investigations of the Navbeta1b sodium channel subunit in human ventricle;
      functional characterization of the H162P Brugada syndrome mutant.
AB  - Brugada syndrome (BrS) is a rare inherited disease that can give rise to
      ventricular arrhythmia and ultimately sudden cardiac death. Numerous loss-of
      function mutations in the cardiac sodium channel Nav1.5 have been associated with
      BrS. However, few mutations in the auxiliary Navbeta1-4 subunits have been linked
      to this disease. Here we investigated differences in expression and function
      between Navbeta1 and Navbeta1b and whether the H162P/Navbeta1b mutation found in
      a BrS patient is likely to be the underlying cause of disease. The impact of
      Navbeta subunits was investigated by patch-clamp electrophysiology, and the
      obtained in vitro values were used for subsequent in silico modeling. We found
      that Navbeta1b transcripts were expressed at higher levels than Navbeta1
      transcripts in the human heart. Navbeta1 and Navbeta1b coexpressed with Nav1.5
      induced a negative shift on steady state of activation and inactivation compared
      with Nav1.5 alone. Furthermore, Navbeta1b was found to increase the current level
      when coexpressed with Nav1.5, Navbeta1b/H162P mutated subunit peak current
      density was reduced by 48% (-645 +/- 151 vs. -334 +/- 71 pA/pF), V1/2 steady
      state inactivation shifted by -6.7 mV (-70.3 +/- 1.5 vs. -77.0 +/- 2.8 mV), and
      time-dependent recovery from inactivation slowed by >50% compared with
      coexpression with Navbeta1b wild type. Computer simulations revealed that these
      electrophysiological changes resulted in a reduction in both action potential
      amplitude and maximum upstroke velocity. The experimental data thereby indicate
      that Navbeta1b/H162P results in reduced sodium channel activity functionally
      affecting the ventricular action potential. This result is an important
      replication to support the notion that BrS can be linked to the function of
      Navbeta1b and is associated with loss-of-function of the cardiac sodium channel.

PMID- 24561867
TI  - Incidence and prognostic factors of c5 palsy: a clinical study of 1001 cases and
      review of the literature.
AB  - BACKGROUND: C5 palsy is a known cause of postoperative deltoid weakness.
      Prognostic variables affecting the incidence of the palsy have been poorly
      understood. OBJECTIVE: To determine the incidence and perioperative
      characteristics/predictors of C5 palsy after anterior vs posterior operations.
      METHODS: All patients undergoing C4-5 operations for degenerative conditions were
      retrospectively reviewed over 21 years. Anterior operations included an anterior
      cervical discectomy and fusion (ACDF) or a corpectomy, whereas posterior
      operations included laminectomy and fusion (+/- foraminotomies). RESULTS: Of the
      total 1001 operations, in 49.0% anterior and 51.0% posterior cases, there was an
      overall C5 palsy incidence of 5.2% (52 cases): 1.6% and 8.6%, respectively (P <
      .001). Of the 99 corpectomies, the palsy incidence of 4.0% was not only higher
      than ACDFs (1.0%), but also followed an upward trend with increasing corpectomy
      levels (P = .009). Of the 69 posterior and 83 anterior C4-5 foraminotomies, the
      incidence of C5 palsy was statistically higher in the posterior (14.5%) vs
      anterior (2.4%) cohort (P = .01). Multiple logistical regression identified older
      age as the strongest predictor of C5 palsy in the anterior (P = .02) and C4-5
      foraminotomy in the posterior (P = .06) cohort. This condition improved within 3
      to 6 months in 75% of patients in the anterior and 88.6% in the posterior cohort
      after a mean follow-up of 14.4 and 27.6 months, respectively. CONCLUSION: In one
      of the largest cohorts on C5 palsy, we found in anterior operations an increasing
      number of corpectomy levels had a higher incidence of C5 palsy; however, older
      age was the strongest predictor of C5 palsy. In posterior operations, C4-5
      foraminotomy carried the strongest correlation.

PMID- 24561868
TI  - Microsurgical anatomy of subtotal temporal bone resection en bloc with the
      parotid gland and temporomandibular joint.
AB  - BACKGROUND: Subtotal temporal bone resection (STBR) has been used for half a
      century to remove temporal bone malignancies. However, there are few reports on
      the detailed anatomy involved in the resection. OBJECTIVE: To describe the
      microsurgical anatomy of STBR combined en bloc with the resection of the parotid
      gland and temporomandibular joint (TMJ). METHODS: Cadaveric specimens were
      dissected in a stepwise manner using 3* to 40* magnification. RESULTS: STBR can
      be combined with the total parotidectomy and the resection of the TMJ if the
      tumor extends into the parotid gland, TMJ, or facial nerve. In this study, we
      describe the step-by-step microsurgical anatomy of STBR en bloc with the parotid
      gland and TMJ. The surgical technique described combines 3 approaches: the high
      cervical, subtemporal-infratemporal fossa, and retromastoid-paracondylar
      approaches. Combining these 3 approaches aided in efficiently completing this
      modified approach. CONCLUSION: STBR is a complicated and technically challenging
      procedure. This study highlights the importance of understanding the surgical
      anatomy of STBR and will serve as a catalyst for improvement of the surgical
      technique for temporal bone resection.

PMID- 24561869
TI  - Classification of the superior petrosal veins and sinus based on drainage
      pattern.
AB  - BACKGROUND: The increasing number of reports of complications after sacrificing
      the superior petrosal veins, the largest veins in the posterior fossa, has led to
      a need for an increased understanding of the anatomy of these veins and the
      superior petrosal sinus into which they empty. OBJECTIVE: To examine the anatomy
      of the superior petrosal veins and their size, draining area, and tributaries, as
      well as the anatomic variations of the superior petrosal sinus. METHOD: Injected
      cadaveric cerebellopontine angles and 3-dimensional multifusion angiography
      images were examined. RESULTS: The 4 groups of the superior petrosal veins based
      on their tributaries, course, and draining areas are the petrosal, posterior
      mesencephalic, anterior pontomesencephalic, and tentorial groups. The largest
      group was the petrosal group. Its largest tributary, the vein of the
      cerebellopontine fissure, was usually identifiable in the suprafloccular cistern
      located above the flocculus on the lateral surface of the middle cerebellar
      peduncle. The medial or lateral segment of the superior petrosal sinus was absent
      in 40% of cerebellopontine angles studied with venography. CONCLUSION: The
      superior petrosal veins and their largest tributaries, especially the vein of the
      cerebellopontine fissure, should be preserved if possible. Obliteration of
      superior petrosal sinuses in which either the lateral or medial portion is absent
      may result in loss of the drainage pathway of the superior petrosal veins.
      Preoperative assessment of the superior petrosal sinus should be considered
      before transpetrosal surgery in which the superior petrosal sinus may be
      obliterated.

PMID- 24561870
TI  - New imaging approaches to evaluate newborn brain injury and their role in
      predicting developmental disorders.
AB  - PURPOSE OF REVIEW: This review highlights recent work using advanced imaging
      approaches that have improved our understanding of the underlying neural
      mechanisms associated with disrupted brain development or demonstrated the
      potential of MRI to provide objective biomarkers of cerebral injury that relate
      to subsequent neurodevelopmental performance. RECENT FINDINGS: Preterm birth
      impacts on the development of thalamocortical connections to inferior frontal and
      medial temporal cortex, and cingulate gyri. Impairments to cortical development
      in these regions are evident in early adulthood and associated with lower
      intelligence quotient scores. Disruptions to microstructural development of
      cortical gray matter are prevalent in survivors of preterm birth and related to
      immaturity at birth, postnatal growth and neurodevelopmental performance. Brain
      dysmaturation is also evident in infants with congenital heart disease and is
      detectable prior to surgery, highlighting the influence of adverse conditions on
      in-utero brain development. In infants with hypoxic-ischemic encephalopathy who
      have undergone therapeutic hypothermia, quantitative magnetic resonance measures
      in the neonatal period are related to performance at 2 years. SUMMARY: Advanced
      MRI approaches offer the opportunity to assess objectively brain structure and
      function, and a number of studies, spanning different patient groups, demonstrate
      their utility as early biomarkers of altered neurological outcome.

PMID- 24561866
TI  - Exercise performance and peripheral vascular insufficiency improve with AMPK
      activation in high-fat diet-fed mice.
AB  - Intermittent claudication is a form of exercise intolerance characterized by
      muscle pain during walking in patients with peripheral artery disease (PAD).
      Endothelial cell and muscle dysfunction are thought to be important contributors
      to the etiology of this disease, but a lack of preclinical models that
      incorporate these elements and measure exercise performance as a primary end
      point has slowed progress in finding new treatment options for these patients. We
      sought to develop an animal model of peripheral vascular insufficiency in which
      microvascular dysfunction and exercise intolerance were defining features. We
      further set out to determine if pharmacological activation of 5'-AMP-activated
      protein kinase (AMPK) might counteract any of these functional deficits. Mice
      aged on a high-fat diet demonstrate many functional and molecular characteristics
      of PAD, including the sequential development of peripheral vascular
      insufficiency, increased muscle fatigability, and progressive exercise
      intolerance. These changes occur gradually and are associated with alterations in
      nitric oxide bioavailability. Treatment of animals with an AMPK activator, R118,
      increased voluntary wheel running activity, decreased muscle fatigability, and
      prevented the progressive decrease in treadmill exercise capacity. These
      functional performance benefits were accompanied by improved mitochondrial
      function, the normalization of perfusion in exercising muscle, increased nitric
      oxide bioavailability, and decreased circulating levels of the endogenous
      endothelial nitric oxide synthase inhibitor asymmetric dimethylarginine. These
      data suggest that aged, obese mice represent a novel model for studying exercise
      intolerance associated with peripheral vascular insufficiency, and
      pharmacological activation of AMPK may be a suitable treatment for intermittent
      claudication associated with PAD.

PMID- 24561871
TI  - Process of cortical network formation and impact of early brain damage.
AB  - PURPOSE OF REVIEW: The aim is to review mechanisms that are central to the
      formation of proper cortical circuitry and relevant to perinatal brain injury and
      premature birth. RECENT FINDINGS: Clinical investigations using noninvasive
      imaging techniques suggest that impaired connectivity of cortical circuitry is
      associated with perinatal adverse conditions. Recent experimental and
      translational studies revealed developmental mechanisms that are critical for
      circuit formation and potentially at risk in the perinatal period. These include
      existence of last wave genesis, migration and integration of gamma-aminobutyric
      acid (GABA) interneurons in the perinatal period; maturation of GABA interneuron
      networks that are central to critical period plasticity; transient connections by
      subplate neurons that guide thalamocortical connectivity, and a perineuronal
      microglia network that maintains axonal growth and neuronal survival as well as
      executing synaptic pruning. In addition, recent work has demonstrated that birth
      plays a key role in triggering the maturation cascade of cortical circuits.
      SUMMARY: Altered maturation of cortical circuits is an increasingly recognized
      aspect of perinatal injury and premature birth. Potential mechanisms are revealed
      but further translational studies are required to associate fine changes at the
      cellular and molecular level with imaging data in experimental models.

PMID- 24561872
TI  - Methods for the modulation and analysis of NF-kappaB-dependent adult
      neurogenesis.
AB  - The hippocampus plays a pivotal role in the formation and consolidation of
      episodic memories, and in spatial orientation. Historically, the adult
      hippocampus has been viewed as a very static anatomical region of the mammalian
      brain. However, recent findings have demonstrated that the dentate gyrus of the
      hippocampus is an area of tremendous plasticity in adults, involving not only
      modifications of existing neuronal circuits, but also adult neurogenesis. This
      plasticity is regulated by complex transcriptional networks, in which the
      transcription factor NF-kappaB plays a prominent role. To study and manipulate
      adult neurogenesis, a transgenic mouse model for forebrain-specific neuronal
      inhibition of NF-kappaB activity can be used. In this study, methods are
      described for the analysis of NF-kappaB-dependent neurogenesis, including its
      structural aspects, neuronal apoptosis and progenitor proliferation, and
      cognitive significance, which was specifically assessed via a dentate gyrus (DG)
      dependent behavioral test, the spatial pattern separation-Barnes maze (SPS-BM).
      The SPS-BM protocol could be simply adapted for use with other transgenic animal
      models designed to assess the influence of particular genes on adult hippocampal
      neurogenesis. Furthermore, SPS-BM could be used in other experimental settings
      aimed at investigating and manipulating DG-dependent learning, for example, using
      pharmacological agents. 

PMID- 24561873
TI  - [Sexual and reproductive health needs in students of a Mexican public
      university].

PMID- 24561875
TI  - Measurement and analysis of atomic hydrogen and diatomic molecular AlO, C2, CN,
      and TiO spectra following laser-induced optical breakdown.
AB  - In this work, we present time-resolved measurements of atomic and diatomic
      spectra following laser-induced optical breakdown. A typical LIBS arrangement is
      used. Here we operate a Nd:YAG laser at a frequency of 10 Hz at the fundamental
      wavelength of 1,064 nm. The 14 nsec pulses with anenergy of 190 mJ/pulse are
      focused to a 50 um spot size to generate a plasma from optical breakdown or laser
      ablation in air. The microplasma is imaged onto the entrance slit of a 0.6 m
      spectrometer, and spectra are recorded using an 1,800 grooves/mm grating an
      intensified linear diode array and optical multichannel analyzer (OMA) or an
      ICCD. Of interest are Stark-broadened atomic lines of the hydrogen Balmer series
      to infer electron density. We also elaborate on temperature measurements from
      diatomic emission spectra of aluminum monoxide (AlO), carbon (C2), cyanogen (CN),
      and titanium monoxide (TiO). The experimental procedures include wavelength and
      sensitivity calibrations. Analysis of the recorded molecular spectra is
      accomplished by the fitting of data with tabulated line strengths. Furthermore,
      Monte-Carlo type simulations are performed to estimate the error margins. Time
      resolved measurements are essential for the transient plasma commonly encountered
      in LIBS.

PMID- 24561876
TI  - Excessive abundance of common resources deters social responsibility.
AB  - We study the evolution of cooperation in the collective-risk social dilemma game,
      where the risk is determined by a collective target that must be reached with
      individual contributions. All players initially receive endowments from the
      available amount of common resources. While cooperators contribute part of their
      endowment to the collective target, defectors do not. If the target is not
      reached, the endowments of all players are lost. In our model, we introduce a
      feedback between the amount of common resources and the contributions of
      cooperators. We show that cooperation can be sustained only if the common
      resources are preserved but never excessively abound. This, however, requires a
      delicate balance between the amount of common resources that initially exist, and
      the amount cooperators contribute to the collective target. Exceeding critical
      thresholds in either of the two amounts leads to loss of cooperation, and
      consequently to the depletion of common resources. 

PMID- 24561877
TI  - Meeting the challenge in performance management: the diffusion and implementation
      of the balanced scorecard in Chinese hospitals.
AB  - The bonus system used in Chinese hospitals has been criticized for eroding
      doctors' professional ethics and aggravating patient expense. This research
      article focuses on one system to improve hospital performance, the balanced
      scorecard (BSC). We use three data sources to examine the diffusion and
      implementation of the BSC in China: a questionnaire survey in Shandong Province,
      a print-media indicators and content analysis of the published BSC papers and
      semi-structured interviews with managers of Chinese hospitals that use the BSC.
      The research evidence shows that bonus systems are important, partially because
      of the poor pay of hospital professionals, and the BSC is perceived as providing
      a fair system to award such bonuses. This helps explain the relative endurance of
      the BSC in Chinese hospitals. 

PMID- 24561874
TI  - An unexpected journey: lysine methylation across the proteome.
AB  - The dynamic modification of histone proteins by lysine methylation has emerged
      over the last decade as a key regulator of chromatin functions. In contrast, our
      understanding of the biological roles for lysine methylation of non-histone
      proteins has progressed more slowly. Though recently it has attracted less
      attention, epsilon-methyl-lysine in non-histone proteins was first observed over
      50 years ago. In that time, it has become clear that, like the case for histones,
      non-histone methylation represents a key and common signaling process within the
      cell. Recent work suggests that non-histone methylation occurs on hundreds of
      proteins found in both the nucleus and the cytoplasm, and with important
      biomedical implications. Technological advances that allow us to identify lysine
      methylation on a proteomic scale are opening new avenues in the non-histone
      methylation field, which is poised for dramatic growth. Here, we review
      historical and recent findings in non-histone lysine methylation signaling,
      highlight new methods that are expanding opportunities in the field, and discuss
      outstanding questions and future challenges about the role of this fundamental
      post-translational modification (PTM).

PMID- 24561878
TI  - An analysis of government immunization program expenditures in lower and lower
      middle income countries 2006-12.
AB  - Financing is becoming increasingly important as the cost of immunizing the
      world's children continues to rise. By 2015, that cost will likely exceed US$60
      per infant as new vaccines are introduced into national immunization programs. In
      2006, 51 lower and lower middle income countries reported spending a mean US$12
      per surviving infant on routine immunization. By 2012, the figure had risen to
      $20, a 67% increase. This study tests the hypothesis that lower and lower middle
      income countries will spend more on their routine immunization programs as their
      economies grow. A panel data regression approach is used. Expenditures reported
      by governments annually (2006-12) through the World Health Organization/UNICEF
      Joint Reporting Form are regressed on lagged annual per capita gross national
      income (GNI), controlling for prevailing mortality levels, immunization program
      performance, corruption control efforts, geographical region and correct
      reporting. Results show the expenditures increased with GNI. Expressed as an
      elasticity, the countries spent approximately $6.32 on immunization for every
      $100 in GNI increase from 2006 to 2012. Projecting forward and assuming continued
      annual GNI growth rates of 10.65%, countries could be spending $60 per infant by
      2020 if national investment functions increase 4-fold. Given the political will,
      this result implies countries could fully finance their routine immunization
      programs without cutting funding for other programs. 

PMID- 24561879
TI  - Health seeking behaviour and the related household out-of-pocket expenditure for
      chronic non-communicable diseases in rural Malawi.
AB  - Malawi is facing a rising chronic non-communicable disease (CNCD) epidemic. This
      study explored health seeking behaviour and related expenditure on CNCDs in rural
      Malawi, with specific focus on detecting potential differences across population
      groups. We used data from the first round of a panel household health survey
      conducted in rural Malawi between August and October 2012 on a sample of 1199
      households. Multinomial logistic regression was used to analyse factors
      associated with health seeking choices for CNCDs, distinguishing between no care,
      informal care and formal care. Descriptive statistics (mean, standard deviation
      and median) were used to describe related household out-of-pocket expenditure.
      There were 475 individuals (equivalent to 8.4% of all respondents) reporting at
      least one CNCD. Among them, 37.3% did not seek any care, 42.5% sought formal care
      (facility-based care), and 20.2% opted for informal care (traditional or home
      treatment). Regression analysis showed that illness severity and duration, socio
      economic status, being a household head, and the proportion of household members
      living with a CNCD were significantly associated with health care utilization.
      Among those seeking care, 65.8% incurred out-of-pocket expenditure with an
      average of USD 1.49 spent on medical treatment and an additional USD 0.50 spent
      on transport. Further qualitative inquiry is needed to understand the reasons for
      low service utilization and to explore the potential role of supply-side factors.
      To increase access to care for people suffering from CNCDs, the provision of a
      free Essential Health Package in Malawi ought to be strengthened through the
      integration of system-wide screening, risk factor modification and continuity of
      care options for people suffering from CNCDs. This would ensure affordable
      services to modulate health seeking behaviour of patients at risk of major
      chronic illnesses. 

PMID- 24561880
TI  - Views of residents of rural areas on accessibility to specialist care through
      videoconference.
AB  - BACKGROUND: Accessibility to specialized health care is important for residents
      in rural areas. Videoconsultation can provide increased accessibility to health
      care. Before implementation of new technologies, it is important to study
      residents' views. OBJECTIVE: This study describes views of residents of rural
      areas on accessibility to specialist care and the use of videoconsultation as
      tool to increase accessibility. METHOD: A questionnaire was distributed via the
      primary health care centres in rural areas of northern Sweden. Data was analysed
      with both quantitative and qualitative methods. RESULTS: The quantitative
      analysis revealed three main areas: savings in time, environmental damage and
      cost of not having to travel were important; security of information must be
      coupled with increased availability of specialist care; responses depended on an
      individual's specific health care needs. The open-ended answers resulted into two
      categories: 1) experiences related to availability of specialist care and 2)
      views on participating in VC. CONCLUSION: Despite the fact that rural residents
      considered the distance as important factor in access to care, there was
      uncertainty regarding videoconsultation as solution. Although respondents were
      familiar with different types of communication technologies, they probably
      hesitated because they did not have information on what videoconsultation would
      mean to them.

PMID- 24561881
TI  - Heart rate variability in patients with severe chronic obstructive pulmonary
      disease in a home care program.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) patients present
      functional and structural changes of the respiratory system that have a profound
      influence on cardiac autonomic dysfunction. OBJETIVE: To analyse heart rate
      variability in COPD patients under stable condition and during acute exacerbation
      episodes (AECOPD). METHODS: Twenty three severe COPD male patients, 69.6 +/- 7.3
      years, in stable condition were followed up for two years. Home visits were
      carried out by a nurse every month, and home or hospital visits were arranged on
      demand. Every three months an ECG, oxygen saturation and spirometric recording
      was obtained for each patient. If the patient presented AECOPD compatible
      clinical data the same measurements were performed before any change of
      treatment. Spectral parameters of heart rate variability in time and frequency
      domains were obtained from ECG. The time evolution of power in low frequency (LF)
      and high frequency (HF) bands were obtained from the spectrogram. In addition, we
      calculated the LF/HF ratio and total heart rate variability power (POW). RESULTS:
      We analysed 154 patient-visit records during the follow up, pertaining to 23
      patients and 8 controls; 19 of the patients had experienced at least one AECOPD.
      Stable COPD patients had higher HF values than control subjects. No significant
      differences were found in LF, LF/HF ratio or POW variables. AECOPD patients had
      higher LF, HF and POW than the stable COPD and control groups. CONCLUSION: AECOPD
      patients exhibited signs of increased autonomic activity compared with stable
      COPD.

PMID- 24561882
TI  - An investigation into the perceptual embodiment of an artificial hand using
      transcutaneous electrical nerve stimulation (TENS) in intact-limbed individuals.
AB  - BACKGROUND: Perceptual embodiment of an artificial limb aids manual control of
      prostheses and can be facilitated by somatosensory feedback. We hypothesised that
      transcutaneous electrical nerve stimulation (TENS) may facilitate perceptual
      embodiment of artificial limbs. OBJECTIVE: To determine the effect of TENS on
      perceptual embodiment of an artificial hand in 32 intact-limbed participants.
      METHODS: Participants were exposed to four experimental conditions in four
      counterbalanced blocks: (i) Vision (V) watching an artificial hand positioned
      congruently to the real hand (out of view); (ii) Vision and strong non-painful
      TENS in the real hand (V+T); Vision and Stroking (V+S) of the artificial and real
      hand with a brush; Vision, Stroking and TENS (V+S+T) watching artificial hand
      being stroked whilst real hand was stroked and receiving TENS. RESULTS: Repeated
      measure ANOVA detected effects for Condition (P< 0.001), Block (P< 0.001) and
      Condition x Block interaction (P< 0.001). Pairwise comparisons detected more
      intense perceptual embodiment for V+S+T compared with V (P< 0.001) and V+T (P<
      0.001), and for V+S compared with V (P< 0.001) and V+T (P< 0.001).The intensity
      of perceptual embodiment increased for later blocks (P< 0.001). CONCLUSIONS: A
      sensation of TENS was generated within the artificial hand in individuals with
      intact limbs and this facilitated perceptual embodiment. The magnitude of effect
      was modest.

PMID- 24561883
TI  - A cloud medication safety support system using QR code and Web services for
      elderly outpatients.
AB  - BACKGROUND: Drug is an important part of disease treatment, but medication errors
      happen frequently and have significant clinical and financial consequences. The
      prevalence of prescription medication use among the ambulatory adult population
      increases with advancing age. Because of the global aging society, outpatients
      need to improve medication safety more than inpatients. OBJECTIVE: The elderly
      with multiple chronic conditions face the complex task of medication management.
      To reduce the medication errors for the elder outpatients with chronic diseases,
      a cloud medication safety supporting system is designed, demonstrated and
      evaluated. METHODS: The proposed system is composed of a three-tier architecture:
      the front-end tier, the mobile tier and the cloud tier. The mobile tier will host
      the personalized medication safety supporting application on Android platforms
      that provides some primary functions including reminders for medication,
      assistance with pill-dispensing, recording of medications, position of
      medications and notices of forgotten medications for elderly outpatients.
      Finally, the hybrid technology acceptance model is employed to understand the
      intention and satisfaction level of the potential users to use this mobile
      medication safety support application system. RESULTS: The result of the system
      acceptance testing indicates that this developed system, implementing patient
      centered services, is highly accepted by the elderly. CONCLUSION: This proposed M
      health system could assist elderly outpatients' homecare in preventing medication
      errors and improving their medication safety.

PMID- 24561884
TI  - A novel evaluation index for adolescent idiopathic scoliosis progression
      measurement and diagnosis.
AB  - Adolescent idiopathic scoliosis is a trunk deformity of the spine with lateral
      deviation and rotation in the transverse plane. The most traditional measurement
      index and parameter for scoliosis diagnosis is the Cobb's angle, which evaluates
      the curves of the scoliotic spine on the radiographic projection of the trunk.
      Although this method is widely accepted as the benchmark in scoliosis assessment,
      it has some limitations and restrictions in practical applications because it is
      measured on a PA (posterior-anterior or back to front) X-ray image, such as
      potential harmfulness from radiation exposure and high cost.In this paper, a
      novel evaluation index for adolescent idiopathic scoliosis measurement and
      diagnosis is introduced to complement the existing assessment index, such as the
      Cobb's angle, the differences of shoulder height, etc. The new evaluation index
      is based on the phenomenon of the tilt and deviation of the vertebras in a
      scoliotic spine, which forms the tilt angles between each pair of adjacent
      vertebras.A data sample of 30 X-ray images of scoliotic spines was used in this
      research to evaluate and examine the usability and validity of the new index. The
      Cobb's angle and the new index were calculated and compared using the same data
      sample. The correlation between the Cobb's angle and the index was also
      determined, and a high correlation is found which demonstrated the usefulness of
      this proposed index. In this paper, it has been shown that the newly-proposed
      index has the potential to be used as a tool to support the traditional scoliosis
      measurement methods.This method can also be generalized on the sagittal plane to
      define other evaluation indices for assessing the severity of kyphosis and
      lordosis. The idea of using angular separation to evaluate spinal deformity in
      multiple planes or in three-dimensional spaces will be discussed in future
      research. 

PMID- 24561885
TI  - Proximal to distal approach in the treatment of tandem occlusions causing an
      acute stroke.
AB  - INTRODUCTION: A tandem occlusion is a rare presentation of acute stroke that
      involves an occlusion of the internal carotid artery at the bifurcation with an
      intracranial middle cerebral artery occlusion. This study describes the
      experience at our institution in treating tandem occlusions with a proximal to
      distal approach in the acute stroke setting. METHODS: A retrospective review of
      acute strokes caused by tandem occlusions requiring thrombectomy were performed.
      RESULTS: 16 cases were identified with a mean National Institutes of Health
      Stroke Scale score at presentation of 13.1 +/- 3.9. The proximal occlusion was
      crossed initially with a microwire in all cases. All carotid occlusions were
      treated with stenting, and intracranial vessel thrombectomy was performed with a
      variety of devices. Procedure related complications occurred in two (12.5%)
      patients. Eight patients (50%) achieved a good outcome (modified Rankin Scale
      score of 0-2). CONCLUSIONS: A tandem occlusion of the carotid artery at the
      bifurcation with a concomitant intracranial occlusion is a relatively rare and
      complex presentation of acute stroke. We have found that addressing the proximal
      lesion first and covering it with a stent prior to performing distal thrombectomy
      appears to be a safe and effective option in the treatment algorithm.

PMID- 24561888
TI  - Phase evolution for conversion reaction electrodes in lithium-ion batteries.
AB  - The performance of battery materials is largely governed by structural and
      chemical evolutions during electrochemical reactions. Therefore, resolving
      spatially dependent reaction pathways could enlighten mechanistic understanding,
      and enable rational design for rechargeable battery materials. Here, we present a
      phase evolution panorama via spectroscopic and three-dimensional imaging at
      multiple states of charge for an anode material (that is, nickel oxide
      nanosheets) in lithium-ion batteries. We reconstruct the three-dimensional
      lithiation/delithiation fronts and find that, in a fully electrolyte immersion
      environment, phase conversion can nucleate from spatially distant locations on
      the same slab of material. In addition, the architecture of a lithiated nickel
      oxide is a bent porous metallic framework. Furthermore, anode-electrolyte
      interphase is found to be dynamically evolving upon charging and discharging. The
      present study has implications for resolving the inhomogeneity of the general
      electrochemically driven phase transition (for example, intercalation reactions)
      and for the origin of inhomogeneous charge distribution in large-format battery
      electrodes. 

PMID- 24561887
TI  - Household effectiveness vs. laboratory efficacy of point-of-use chlorination.
AB  - Treatment of water at the household level offers a promising approach to combat
      the global burden of diarrheal diseases. In particular, chlorination of drinking
      water has been a widely promoted strategy due to persistence of residual chlorine
      after initial treatment. However, the degree to which chlorination can reduce
      microbial levels in a controlled setting (efficacy) or in a household setting
      (effectiveness) can vary as a function of chlorine characteristics, source water
      characteristics, and household conditions. To gain more understanding of these
      factors, we carried out an observational study within households in rural
      communities of northern coastal Ecuador. We found that the efficacy of chlorine
      treatment under controlled conditions was significantly better than its household
      effectiveness when evaluated both by ability to meet microbiological safety
      standards and by log reductions. Water treated with chlorine achieved levels of
      microbial contamination considered safe for human consumption after 24 h of
      storage in the household only 39-51% of the time, depending on chlorine treatment
      regimen. Chlorine treatment would not be considered protective against diarrheal
      disease according to WHO log reduction standards. Factors that explain the
      observed compromised effectiveness include: source water turbidity, source water
      baseline contamination levels, and in-home contamination. Water in 38% of the
      households that had low turbidity source water (<10 NTU) met the safe water
      standard as compared with only 17% of the households that had high turbidity
      source water (>10 NTU). A 10 MPN/100 mL increase in baseline Escherichia coli
      levels was associated with a 2.2% increase in failure to meet the E. coli
      standard. Higher mean microbial contamination levels were seen in 54% of
      household samples in comparison to their matched controls, which is likely the
      result of in-home contamination during storage. Container characteristics (size
      of the container mouth) did not influence chlorine effectiveness. We found no
      significant differences between chlorine treatment regimens in ability to meet
      the safe water standards or in overall log reductions, although chlorine dosage
      did modify the effect of source conditions. These results underscore the
      importance of measuring both source water and household conditions to determine
      appropriate chlorine levels, as well as to evaluate the appropriateness of
      chlorine treatment and other point-of-use water quality improvement
      interventions. 

PMID- 24561889
TI  - Culture of isolated floor plate tissue and production of conditioned medium to
      assess functional properties of floor plate-released signals.
AB  - During development, progenitors and post-mitotic neurons receive signals from
      adjacent territories that regulate their fate. The floor-plate is a group of
      glial cells lining the ependymal canal at ventral position. The floor-plate
      expresses key morphogens contributing to the patterning of cell lineages in the
      spinal cord. At later developmental stages, the floor-plate regulates the
      navigation of axons in the spinal cord, acting as a barrier to prevent the
      crossing of ipsilateral axons and controlling midline crossing by commissural
      axons(1). These functions are achieved through the secretion of various guidance
      cues. Some of these cues act as attractants and repellents for the growing axons
      while others regulate guidance receptors and downstream signaling to modulate the
      sensitivity of the axons to the local guidance cues(2,3). Here we describe a
      method that allows investigating the properties of floor-plate derived signals in
      a variety of developmental contexts, based on the production of Floor-Plate
      conditioned medium (FP(cm))(4-6). We then exemplify the use of this FP(cm) in the
      context of axon guidance. First, the spinal cord is isolated from mouse embryo at
      E12.5 and the floor-plate is dissected out and cultivated in a plasma-thrombin
      matrix (Figure 1). Second two days later, commissural tissue are dissected out
      from E12.5 embryos, triturated and exposed to the FP(cm). Third, the tissue are
      processed for Western blot analysis of commissural markers. 

PMID- 24561890
TI  - Automatic detection of trustworthiness of the face: a visual mismatch negativity
      study.
AB  - Recognizing intentions of strangers from facial cues is crucial in everyday
      social interactions. Recent studies demonstrated enhanced event-related potential
      (ERP) responses to untrustworthy compared to trustworthy faces. The aim of the
      present study was to investigate the electrophysiological correlates of automatic
      processing of trustworthiness cues in a visual oddball paradigm in two
      consecutive experimental blocks. In one block, frequent trustworthy (p = 0.9) and
      rare untrustworthy face stimuli (p = 0.1) were briefly presented on a computer
      screen with each stimulus consisting of four peripherally positioned faces. In
      the other block stimuli were presented with reversed probabilities enabling the
      comparison of ERPs evoked by physically identical deviant and standard stimuli.
      To avoid attentional effects participants engaged in a central detection task.
      Analyses of deviant minus standard difference waveforms revealed that deviant
      untrustworthy but not trustworthy faces elicited the visual mismatch negativity
      (vMMN) component. The present results indicate that adaptation occurred to
      repeated unattended trustworthy (but not untrustworthy) faces, i.e., an automatic
      expectation was elicited towards trustworthiness signals, which was violated by
      deviant untrustworthy faces. As an evolutionary adaptive mechanism, the observed
      fast detection of trustworthiness-related social facial cues may serve as the
      basis of conscious recognition of reliable partners. 

PMID- 24561891
TI  - Protective and antigenotoxic effect of Ulva rigida C. Agardh in experimental
      hypothyroid.
AB  - The presence of chromosomal damage in bone marrow cells affected by several
      diseases such as thyroid, cancer etc., was detected by the micronucleus (MN)
      assay. The present study was designed to evaluate: i) volatile components of Ulva
      rigida, ii) effects of hypothyroidism on bone marrow MN frequency, iii) effects
      of oral administration of Ulva rigida ethanolic extract (URE) on MN frequency
      produced by hypothyroidism, and iv) thyroid hormone levels in normal and 6-n
      Propylthiouracil (PTU)-induced hypothyroid rats. The volatile components of Ulva
      rigida was studied using a direct thermal desorption (DTD) technique with
      comprehensive two-dimensional gas chromatography time-of-flight mass spectrometry
      (GCxGC-TOF/MS). URE administration was of no significant impact on thyroid
      hormone levels in control group, while PTU administration decreased thyroid
      hormone levels compared to control group (p < 0.001). Moreover, URE
      supplementation resulted in a significant decrease in MN frequency in each
      thyroid group (p < 0.0001). This is the first in vivo study that shows the strong
      antigenotoxic and protective effect of URE against the genotoxicity produced by
      hypothyroidism.

PMID- 24561892
TI  - The role of ionizing radiaton on ovulation rate and oocyte morphology in mouse.
AB  - We investigated the effects of ionizing radiation on maturation ability and
      radiosensitivity of oocytes enclosed in preantral and antral follicles. Balb/c
      female mice received total body single dose gamma radiation (7.2 Gy) at the
      diestrous to proestrous transition period. In the first experiment, spontaneously
      ovulated oocytes were collected from irradiated animals. In the second
      experiment, irradiated animals were allowed to superovulate to assess the ovarian
      function. The spontaneous ovulation rate of the follicles exposed at antral stage
      was significantly lower than the sham-irradiated mice (p < 0.01), and most of the
      oocytes were found at the metaphase I stage. Oocyte morphology and the ovulation
      rate of the follicles exposed at preantral stage were similar to the sham
      irradiated group. Minimal morphological abnormalities were observed in the
      oocytes and the polar body as well. The superovulation response of all the
      irradiated animals was lower than the respective control animals. The
      superovulation rate was significantly lower in the first ovulation after
      irradiation (p < 0.01). In conclusion, our findings indicate that total body
      gamma irradiation, on a basis of estrous cycle stages, leads to ovulation failure
      in the antral stage while causes abnormal oocyte morphology in the preantral
      stage follicles in mice. 

PMID- 24561893
TI  - A comparison of the levels of hydroxamic acids in Aegilops speltoides and a
      hexaploid wheat and effects on Rhopalosiphum padi behaviour and fecundity.
AB  - Hydroxamic acids (HAs) are plant secondary metabolites produced by certain
      cereals, which have been found to be toxic to pest aphids in artificial diet
      assays. Previous studies have shown that tetraploid and hexaploid wheat
      varieties, the leaf tissues of which contained higher levels of these compounds
      than used in artificial diets, did not reduce aphid settling or fecundity. This
      current study reports findings on a high HA producing B genome accession of the
      diploid ancestor of wheat, Aegilops speltoides. We found that this accession does
      have a negative impact on aphid host selection and substantially reduces nymph
      production. Whole leaf tissue assays showed very high levels of HAs, well in
      excess of the toxic level determined in the artificial diet assays. Extraction of
      the apoplast fluid (AF) from this accession showed that the HA level is much
      lower than that of the whole tissue, but is still close to the artificial diet
      toxic level. Furthermore the HA level in the AF increases in response to aphid
      feeding. These observations could explain why hexaploid wheat remains susceptible
      to aphids, despite having whole leaf tissue HA levels in excess of the toxic
      levels determined in artificial diets. 

PMID- 24561894
TI  - Waterlogging and nitric oxide induce gene expression and increase antioxidant
      enzyme activity in wheat (Triticum aestivum L.).
AB  - The effects of waterlogging (WL) and WL plus nitric oxide (WL+NO) were
      investigated in seedlings of one wheat cultivars (Triticum aestivum cv.
      Dogankent) and one wheat line (Triticum aestivum cv. Ducula-4). Under WL
      conditions, catalase activity was greater in Ducula-4 than in Dogankent.
      Glutathione reductase activity increased in Ducula-4 seedlings under WL+NO
      conditions, especially at 48 and 72 hours of treatment. Myb2 expression increased
      during the early hours of treatment in both wheat varieties exposed to WL, with
      40-fold higher levels in Ducula-4, gradually decreasing to control levels. Under
      WL+NO treatment, Myb2 expression increased 44-fold at 12 hours and high levels of
      expression were still observed at 72 hours. When Ducula-4 seedlings were
      subjected to WL+NO treatment, PDPK expression increased approximately 15-fold at
      3 hours and decreased to control levels at 72 hours. Under the same conditions,
      SST1 expression increased 3-fold at 3 and 12 hours and reached control levels
      during the subsequent hours. Among the genes studied, the highest level of
      expression was observed for Myb2. Moreover, gene expression was altered most by
      waterlogging in Ducula-4 seedlings. 

PMID- 24561895
TI  - Effect of salinity on moisture content, pigment system, and lipid composition in
      Ephedra alata Decne.
AB  - The present work was carried out to uncover the effect of salinity stress on
      shoot moisture percentage, pigment content and lipid composition of Ephedra alata
      Decne. The results suggested that salinity caused significant decrease in plant
      moisture content. The chl. a, b and carotenoids showed significant decrease with
      increasing concentration of salt. Total pigment content also showed decline at
      all salt stress levels. Salt stress caused significant decrease in total lipids
      (TL), triacylglycerol (TG) and sterol (S) accompanied with an increase in
      diacylglycerol (DG), sterol ester (SE), and non-esterified fatty acids (FAA) of
      E. alata. Moreover, saline stress caused significant decrease in all phospholipid
      fractions except phosphatidic acid which increases during salt stress. Salinity
      stress resulted in increase of saturated fatty acids and decreases the percentage
      of un-saturated fatty acids in E. alalta. 

PMID- 24561896
TI  - Optimization of factors influencing in vitro flowering of gherkin (Cucumis
      anguria L.).
AB  - This study investigated the factors influencing in vitro flowering of gherkin
      (Cucumis anguria L.). Multiple shoots were efficiently regenerated from
      cotyledonary node and axillary bud explants of C. anguria within 15 days on MSB5
      medium containing 3% sucrose and supplemented with 1.5 mg l-1 6-benzyladinine
      (BA). The elongated shoots were excised and transferred to MSB5 medium containing
      4% sucrose supplemented with 0.5 mg l(-1) gibberellic acid (GA(3)) and 1.0 mg l(
      1) indole-3-butyric acid (IBA) induced maximum number of flowers (9.5
      flowers/plant) and root induction (16.5 roots/plant). Factors that influence the
      in vitro flowering were optimizing pH, photoperiod and temperature. In vitro
      flowering was significantly early and higher number of flowers produced at pH
      (5.8), photoperiod (12/12 h) and room temperature (28  degrees C). In vitro
      developed flowers were less viable (80 +/- 1.0%) compared to control plants (90
      +/- 2.0%). Our in vitro flower induction procedures provide an extremely
      effective method for further research on flowering regulation mechanisms in C.
      anguria. These plantlets were successfully transferred to the soil where they
      grew well for 3 to 5 weeks with 90% survivability. Plants grew normally and
      produced flowers with viable pollen and fertile seeds.

PMID- 24561897
TI  - Genoprotectivity of methanol and ethanol extracted leaf sap of Trigonella foenum
      graecum in Allium cepa root assay.
AB  - Fenugreek (Trigonella foenum-graecum) of Fabacecae family is widely distributed
      throughout the world and used as an old medicinal plant and traditional food. The
      present study deals with the investigation of the anti-genotoxic potential of
      methanol (MTG) and ethanol (ETG) extracted leaf sap of fenugreek on Allium cepa
      root tip cells, which were treated with cadmium sulfate (CdSO(4)). Three types of
      treatments were applied. First, roots were treated with different concentrations
      of methanolic and ethanolic extracts (0.1%, 0.5% and 1%) separately for 3 h each,
      followed by CdSO(4) treatment (at 250 ppm, for 3 h). Second, roots were first
      treated with CdSO(4) followed by extracts treatment. Third, root tips were
      treated with CdSO(4) with extracts treatments at the same time. For controls,
      roots with CdSO(4) (250 ppm) and distilled water served as positive and negative
      control, respectively. The results showed that the methanol and ethanol extracts
      of fenugreek modulated the genotoxic and clastogenic aberrations, which were
      induced by CdSO(4). The protection activity of MTG (1%) was 50% in the first
      treatment, 70% in the second treatment and 82% in the third treatment and 61%,
      68% and 88% of ETG (1%), respectively. DNA rearrangements were also observed by
      revealing new RAPD bands in the total DNS samples isolated from Allium roots
      after treatmenst.

PMID- 24561898
TI  - Leaf litter decomposition in Torna stream before and after a red mud disaster.
AB  - The aim of the study was to estimate the breakdown of the allochthonous litter in
      an artificial stream running in an agricultural area and compare it with the same
      values following a toxic mud spill into the same stream. Litter bags were filled
      with three types of leaves (Quercus robur, Populus tremula and Salix alba) and
      placed to the bottom of the river. Ergosterol was used to detect fungal biomass.
      We supposed the absence of fungi and the retardation of leaf litter
      decomposition. Only pH and conductivity increased significantly. Leaf mass loss
      after the catastrophe was much slower than in 2009 and the decay curves did not
      follow the exponential decay model. Prior to the catastrophe, leaf mass loss was
      fast in Torna, compared to other streams in the area. The reason is that the
      stream is modified, the bed is trapezoid and covered with concrete stones. Fungal
      biomass was lower, than in the pre-disaster experiment, because fungi did not
      have enough leaves to sporulate. Leaf mass loss followed the exponential decay
      curve before the disaster, but after that it was possible only after a non-change
      period. 

PMID- 24561899
TI  - In vitro antifugal activity of medicinal plant extract against Fusarium oxysporum
      f. sp. lycopersici race 3 the causal agent of tomato wilt.
AB  - Medicinal plant extracts of five plants; Adhatoda vasica, Eucalyptus globulus,
      Lantana camara, Nerium oleander and Ocimum basilicum collected from Cairo, Egypt
      were evaluated against Fusarium oxysporum f. sp. lycopersici race 3 in vitro
      conditions using water and certain organic solvents. The results revealed that
      cold distilled water extracts of O. basilicum and E. globulus were the most
      effective ones for inhibiting the growth of F. oxysporum f. sp. lycopersici.
      Butanolic and ethanolic extracts of the tested plants inhibited the pathogen
      growth to a higher extent than water extracts. Butanolic extract of O. basilicum
      completely inhibited the growth of F. oxysporum f. sp. lycopersici at
      concentrations 1.5 and 2.0% (v/v). Butanolic extracts (2.0%) of tested plants had
      a strong inhibitory effect on hydrolytic enzymes; beta-glucosidase, pectin lyase
      and protease of F. oxysporum f. sp. lycopersici. This study has confirmed that
      the application of plant extracts, especially from O. basilicum for controlling
      F. oxysporum f. sp. lycopersici is environmentally safe, cost effective and does
      not disturb ecological balance. Investigations are in progress to test the
      efficacy of O. basilicum extract under in vivo conditions. 

PMID- 24561901
TI  - Self-esteem and evaluative beliefs in paranoia.
AB  - BACKGROUND AND OBJECTIVES: Psychological models have implicated negative self
      esteem as an important factor underlying paranoia. However, research
      investigating the role of self-esteem in paranoia suffers from poor conceptual
      and methodological understanding, resulting in conflicting findings. Central to
      this problem is the use of measures investigating global self-esteem and self
      evaluative beliefs interchangeably. In the present study we aimed to analyze
      differences in self-esteem domains and self-evaluation. METHODS: The present
      study used interviews and questionnaires to compare a clinical sample of
      participants who were currently paranoid (n = 55) with healthy controls (n = 57)
      on global self-esteem domains and negative evaluative beliefs, in order to
      investigate the multi-faceted role of "the self". RESULTS: There was no
      significant difference in self-esteem domains between groups, highlighting that
      self-esteem is preserved in currently paranoid individuals. However, the paranoid
      group had significantly more negative evaluative beliefs. Interestingly, our
      global measures of self-esteem and measures of negative evaluative beliefs were
      uncorrelated, highlighting the importance of understanding the differences
      underlying these concepts. LIMITATIONS: This study does not address dynamic
      aspects of self-esteem and self-evaluation. CONCLUSIONS: The present study
      provides undeniable evidence to investigate self-concept dimensions separately.
      These findings must be considered by researchers interested in the role of the
      self in the onset and maintenance of paranoia.

PMID- 24561902
TI  - On the cutting edge.

PMID- 24561904
TI  - Allosteric control of kinesin's motor domain by tubulin: a molecular dynamics
      study.
AB  - Molecular motors such as kinesin are essential for many biological processes.
      These motors have two motor domains, which bind to tubulin filaments, hydrolyze
      ATP, and transduce the released chemical energy into directed movements. The
      general principles of this chemomechanical coupling are now well-established but
      the underlying molecular mechanisms remain elusive because small conformational
      changes within large proteins are difficult to detect experimentally. Here, we
      use atomistic molecular dynamics simulations to monitor such changes within a
      single motor domain of KIF1A, which belongs to the kinesin-3 motor family. The
      nucleotide binding pocket of this domain can be empty or occupied by ATP or ADP.
      For these three nucleotide states, we determine the mobility of the backbone of
      the protein, both in solution and attached to tubulin. Only one subdomain of the
      motor domain is found to exhibit a strongly increased mobility upon binding to
      tubulin: the neck linker that presumably acts as a mechanical transmitter to the
      other motor domain in dimeric kinesin-3 motors. Furthermore, upon binding to
      tubulin, the neck linker mobility becomes sensitive to the bound nucleotide and
      is highly increased after phosphate release, which implies undocking of this
      linker from the core of the motor domain. These simulation results are consistent
      with experimental data from EPR spectroscopy, FRET, and cryo-electron microscopy.
      A detailed analysis of our simulation data also reveals that the undocking of the
      neck linker in the ADP-kinesin-tubulin state arises from allosteric interactions
      between the nucleotide and tubulin and that the beta-sheet core undergoes a twist
      both during phosphate release and ATP binding. The computational approach used
      here can be applied to other motor domains and mechanoenzymes in order to
      identify allosteric interactions between the subdomains of these proteins. 

PMID- 24561903
TI  - Chromatin without the 30-nm fiber: constrained disorder instead of hierarchical
      folding.
AB  - Several hierarchical levels of DNA packaging are believed to exist in chromatin,
      starting from a 10-nm chromatin fiber that is further packed into a 30-nm fiber.
      Transitions between the 30-nm and 10-nm fibers are thought to be essential for
      the control of chromatin transcriptional status. However, recent studies
      demonstrate that in the nuclei, DNA is packed in tightly associated 10-nm fibers
      that are not compacted into 30-nm fibers. Additionally, the accessibility of DNA
      in chromatin depends on the local mobility of nucleosomes rather than on
      decompaction of chromosome regions. These findings argue for reconsidering the
      hierarchical model of chromatin packaging and some of the basic definitions of
      chromatin. In particular, chromatin domains should be considered as three
      dimensional objects, which may include genomic regions that do not necessarily
      constitute a continuous domain on the DNA chain. 

PMID- 24561907
TI  - Spatial coding and attractor dynamics of grid cells in the entorhinal cortex.
AB  - Recent experiments support the theoretical hypothesis that recurrent connectivity
      plays a central role within the medial entorhinal cortex, by shaping activity of
      large neural populations, such that their joint activity lies within a continuous
      attractor. This conjecture involves dynamics within each population (module) of
      cells that share the same grid spacing. In addition, recent theoretical works
      raise a hypothesis that, taken together, grid cells from all modules maintain a
      sophisticated representation of position with uniquely large dynamical range,
      when compared with other known neural codes in the brain. To maintain such a
      code, activity in different modules must be coupled, within the entorhinal cortex
      or through the hippocampus. 

PMID- 24561906
TI  - Combination of immortalization and inducible death strategies to generate a human
      mesenchymal stromal cell line with controlled survival.
AB  - The hTERT-immortalization of human bone marrow-derived Mesenchymal Stromal Cells
      (hMSCs) was proposed to address availability/standardization issues for
      experimental or clinical studies, but raised concerns due to possible
      uncontrolled growth or malignant cell transformation. Here we report a method to
      generate a hMSCs line with controlled survival, through the implementation of a
      pre-established suicide system (inducible caspase 9, iCasp9) in hTERT-transduced
      hMSCs. Primary hMSCs were successfully immortalized (>280 PD) and further
      transduced with the iCasp9 device. A clone was selected and shown to maintain
      typical properties of primary hMSCs, including phenotype, differentiation and
      immunomodulation capacities. The successive transductions did not induce
      tumorigenic transformation, as assessed by analysis of cell cycle regulators and
      in vivo luciferase-based cell tracking. Cells could be efficiently induced toward
      apoptosis (>95%) both in vitro and in vivo. By combining the opposite concepts of
      'induced-life' and 'inducible-death', we generated a hMSCs line with defined
      properties and allowing for temporally controlled survival. The cell line
      represents a relevant tool for medical discovery in regenerative medicine and a
      potential means to address availability, standardization and safety requirements
      in cell & gene therapy. The concept of a hTERT-iCasp9 combination, here explored
      in the context of hMSCs, could be extended to other types of progenitor/stem
      cells. 

PMID- 24561909
TI  - Capturing volatile natural products by mass spectrometry.
AB  - Covering: up to 2013 This review gives a modern methodic overview of how volatile
      natural products from various sources such as plants, animals, bacteria and fungi
      can be trapped and how compound identification can be performed even in cases of
      very low yields or within highly complex compound mixtures. A detailed discussion
      is presented on how a structural proposal for an unknown analyte can be derived
      from GC-MS data. Furthermore, the application of trace analytical techniques in
      biosynthetic studies with isotopically labelled compounds is presented, including
      a discussion of the pros and cons of different kinds of stable isotope labellings
      in GC-MS analyses.

PMID- 24561911
TI  - Structural and thermodynamic factors of suppressed interdiffusion kinetics in
      multi-component high-entropy materials.
AB  - We report multi-component high-entropy materials as extraordinarily robust
      diffusion barriers and clarify the highly suppressed interdiffusion kinetics in
      the multi-component materials from structural and thermodynamic perspectives. The
      failures of six alloy barriers with different numbers of elements, from unitary
      Ti to senary TiTaCrZrAlRu, against the interdiffusion of Cu and Si were
      characterized, and experimental results indicated that, with more elements
      incorporated, the failure temperature of the barriers increased from 550 to 900
      degrees C. The activation energy of Cu diffusion through the alloy barriers was
      determined to increase from 110 to 163 kJ/mole. Mechanistic analyses suggest
      that, structurally, severe lattice distortion strains and a high packing density
      caused by different atom sizes, and, thermodynamically, a strengthened cohesion
      provide a total increase of 55 kJ/mole in the activation energy of substitutional
      Cu diffusion, and are believed to be the dominant factors of suppressed
      interdiffusion kinetics through the multi-component barrier materials.

PMID- 24561912
TI  - All heads are up.

PMID- 24561908
TI  - The H3K27me3 demethylase UTX in normal development and disease.
AB  - In 2007, the Ubiquitously Transcribed Tetratricopeptide Repeat on chromosome X
      (UTX) was identified as a histone demethylase that specifically targets di- and
      tri-methyl groups on lysine 27 of histone H3 (H3K27me2/3). Since then, UTX has
      been proven essential during normal development, as it is critically required for
      correct reprogramming, embryonic development and tissue-specific differentiation.
      UTX is a member of the MLL2 H3K4 methyltransferase complex and its catalytic
      activity has been linked to regulation of HOX and RB transcriptional networks. In
      addition, an H3K27me2/3 demethylase independent function for UTX was uncovered in
      promoting general chromatin remodeling in concert with the BRG1-containing
      SWI/SNF remodeling complex. Constitutional inactivation of UTX causes a specific
      hereditary disorder called the Kabuki syndrome, whereas somatic loss of UTX has
      been reported in a variety of human cancers. Here, we compile the breakthrough
      discoveries made from the first disclosure of UTX as a histone demethylase till
      the identification of disease-related UTX mutations and specific UTX inhibitors. 

PMID- 24561910
TI  - The synthetic biology future.
AB  - Herein, I track the evolution of synthetic biology from its earliest incarnations
      more than 50 years ago, through the DIYbio revolution, to the next 50 years. 

PMID- 24561913
TI  - Clinical pearls.

PMID- 24561915
TI  - A requirement for ER-derived COPII vesicles in phagophore initiation.
AB  - A major unanswered question in the field of autophagy is how the double-membrane
      phagophore is formed. As this membrane expands, it engulfs proteins and
      organelles that are destined for degradation and then seals to form an
      autophagosome. A growing consensus in the field is that a subdomain of the ER
      initiates formation of the phagophore. We show that ER-derived COPII-coated
      vesicles, which bud from a specialized domain of the ER called the ER exit site
      (ERES), are a source of this membrane. This finding will now pave the way for a
      biochemical description of the early steps of phagophore initiation. 

PMID- 24561916
TI  - European decisions about the "Whack-a-mole" game.

PMID- 24561917
TI  - Assessment of age-related changes in cognitive functions using EmoCogMeter, a
      novel tablet-computer based approach.
AB  - The main goal of this study was to assess the usability of a tablet-computer
      based application (EmoCogMeter) in investigating the effects of age on cognitive
      functions across the lifespan in a sample of 378 healthy subjects (age range 18
      89 years). Consistent with previous findings we found an age-related cognitive
      decline across a wide range of neuropsychological domains (memory, attention,
      executive functions), thereby proving the usability of our tablet-based
      application. Regardless of prior computer experience, subjects of all age groups
      were able to perform the tasks without instruction or feedback from an
      experimenter. Increased motivation and compliance proved to be beneficial for
      task performance, thereby potentially increasing the validity of the results. Our
      promising findings underline the great clinical and practical potential of a
      tablet-based application for detection and monitoring of cognitive dysfunction. 

PMID- 24561919
TI  - Imagery-enhanced cognitive behavioural group therapy for social anxiety disorder:
      a pilot study.
AB  - Cognitive behavioural group therapy (CBGT) for social anxiety disorder (SAD) is
      efficacious and effective, however a substantial proportion of patients remain in
      the clinical range so treatment innovations are required. Research suggests that
      working within the imagery mode may be more emotionally potent than traditional
      verbal-linguistic strategies. This study piloted an imagery-enhanced CBGT (IE
      CBGT) protocol for SAD. It was hypothesised that IE-CBGT would be acceptable to
      patients, demonstrate large effect sizes, and compare favourably to historical
      controls who completed CBGT without the imagery-enhancements. Patients (N=19)
      were consecutive referrals to a community clinic specialising in anxiety and mood
      disorders. Primary outcomes were self-reported performance and social interaction
      anxiety. IE-CBGT was highly acceptable to patients with high attendance and
      completion rates. Effect sizes were large by mid-treatment and very large at post
      treatment and follow-up. A high proportion of patients achieved reliable change.
      Outcomes compared favourably to published group and individual treatments for SAD
      but larger randomised controlled trials are now required.

PMID- 24561918
TI  - Understanding the relationship between food environments, deprivation and
      childhood overweight and obesity: evidence from a cross sectional England-wide
      study.
AB  - Using a large cross sectional English sample, we quantified the association
      between weight status in children aged 4-5 and 10-11 year, characteristics of the
      food environment, and area deprivation. We observed a positive association
      between the density of unhealthy food outlets in a neighbourhood and the
      prevalence of overweight and obesity in children. An association in the opposite
      direction was observed for other types of food outlets, although after adjustment
      this was only statistically significant for older children. The prevalence of
      fast food and other unhealthy food outlets explained only a small proportion of
      the observed associations between weight status and socioeconomic deprivation.
      Children's weight status may be influenced by their local environment,
      particularly older children, but associations between obesity and deprivation do
      not appear strongly due to local food environment characteristics. 

PMID- 24561920
TI  - Epistasis between adults and larvae underlies caste fate and fitness in a clonal
      ant.
AB  - In social species, the phenotype and fitness of an individual depend in part on
      the genotype of its social partners. However, how these indirect genetic effects
      affect genotype fitness in competitive situations is poorly understood in animal
      societies. We therefore studied phenotypic plasticity and fitness of two clones
      of the ant Cerapachys biroi in monoclonal and chimeric colonies. Here we show
      that, while clone B has lower fitness in isolation, surprisingly, it consistently
      outcompetes clone A in chimeras. The reason is that, in chimeras, clone B
      produces more individuals specializing in reproduction rather than cooperative
      tasks, behaving like a facultative social parasite. A cross-fostering experiment
      shows that the proportion of these individuals depends on intergenomic epistasis
      between larvae and nursing adults, explaining the flexible allocation strategy of
      clone B. Our results suggest that intergenomic epistasis can be the proximate
      mechanism for social parasitism in ants, revealing striking analogies between
      social insects and social microbes. 

PMID- 24561921
TI  - Teleworkers with disabilities: characteristics and accommodation use.
AB  - BACKGROUND: The prevalence of telework among people with disabilities is not as
      great as the general population, despite the accommodative benefits of telework.
      OBJECTIVE: This study of employment and accommodation use patterns of people with
      disabilities investigates relationships between functional abilities, work
      location and nature, and accommodation use. PARTICIPANTS: Currently employed
      subjects with disabilities were recruited from client lists of research,
      technical assistance, and service provision centers, as well as through over 100
      social networking venues focused on individuals with disabilities. METHODS: A
      national, cross-sectional survey was administered electronically. Details of
      accommodation use for 373 individuals were compared using Chi-Square distribution
      analysis. RESULTS: Those in white-collar and knowledge-based jobs were twice as
      likely to telework as other worker types, and teleworkers were twice as likely to
      use flexible scheduling. Only 47% of teleworkers reported telework as a job
      accommodation. Of those, 57% were satisfied with telework and 76% reported it as
      important to job task completion. CONCLUSIONS: Increased use of flexible
      scheduling, particularly among those who view telework as an accommodation,
      suggests the primary accommodative benefit of telework is to reduce pain and
      fatigue-related barriers to traditional employment. Relatively low satisfaction
      with telework suggests that it presents other employment-related barriers.

PMID- 24561922
TI  - Deep brain stimulation with simultaneous FMRI in rodents.
AB  - In order to visualize the global and downstream neuronal responses to deep brain
      stimulation (DBS) at various targets, we have developed a protocol for using
      blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI)
      to image rodents with simultaneous DBS. DBS fMRI presents a number of technical
      challenges, including accuracy of electrode implantation, MR artifacts created by
      the electrode, choice of anesthesia and paralytic to minimize any neuronal
      effects while simultaneously eliminating animal motion, and maintenance of
      physiological parameters, deviation from which can confound the BOLD signal. Our
      laboratory has developed a set of procedures that are capable of overcoming most
      of these possible issues. For electrical stimulation, a homemade tungsten bipolar
      microelectrode is used, inserted stereotactically at the stimulation site in the
      anesthetized subject. In preparation for imaging, rodents are fixed on a plastic
      headpiece and transferred to the magnet bore. For sedation and paralysis during
      scanning, a cocktail of dexmedetomidine and pancuronium is continuously infused,
      along with a minimal dose of isoflurane; this preparation minimizes the BOLD
      ceiling effect of volatile anesthetics. In this example experiment, stimulation
      of the subthalamic nucleus (STN) produces BOLD responses which are observed
      primarily in ipsilateral cortical regions, centered in motor cortex. Simultaneous
      DBS and fMRI allows the unambiguous modulation of neural circuits dependent on
      stimulation location and stimulation parameters, and permits observation of
      neuronal modulations free of regional bias. This technique may be used to explore
      the downstream effects of modulating neural circuitry at nearly any brain region,
      with implications for both experimental and clinical DBS.

PMID- 24561923
TI  - A novel procedure for evaluating the reinforcing properties of tastants in
      laboratory rats: operant intraoral self-administration.
AB  - This paper describes a novel method for studying the bio-behavioral basis of
      addiction to food. This method combines the surgical component of taste
      reactivity with the behavioral aspects of operant self-administration of drugs.
      Under very brief general anaesthesia, rats are implanted with an intraoral (IO)
      cannula that allows delivery of test solutions directly in the oral cavity.
      Animals are then tested in operant self-administration chambers whereby they can
      press a lever to receive IO infusions of test solutions. IO self-administration
      has several advantages over experimental procedures that involve drinking a
      solution from a spout or operant responding for solid pellets or solutions
      delivered in a receptacle. Here, we show that IO self-administration can be
      employed to study self-administration of high fructose corn syrup (HFCS). Rats
      were first tested for self-administration on a progressive ratio (PR) schedule,
      which assesses the maximum amount of operant behavior that will be emitted for
      different concentrations of HFCS (i.e. 8%, 25%, and 50%). Following this test,
      rats self-administered these concentrations on a continuous schedule of
      reinforcement (i.e. one infusion for each lever press) for 10 consecutive days (1
      session/day; each lasting 3 hr), and then they were retested on the PR schedule.
      On the continuous reinforcement schedule, rats took fewer infusions of higher
      concentrations, although the lowest concentration of HFCS (8%) maintained more
      variable self-administration. Furthermore, the PR tests revealed that 8% had
      lower reinforcing value than 25% and 50%. These results indicate that IO self
      administration can be employed to study acquisition and maintenance of responding
      for sweet solutions. The sensitivity of the operant response to differences in
      concentration and schedule of reinforcement makes IO self-administration an ideal
      procedure to investigate the neurobiology of voluntary intake of sweets.

PMID- 24561924
TI  - Quantifying missing annual emission sources of heavy metals in the United Kingdom
      with an atmospheric transport model.
AB  - An atmospheric chemical transport model was adapted to simulate the concentration
      and deposition of heavy metals (arsenic, cadmium, chromium, copper, lead, nickel,
      selenium, vanadium, and zinc) in the United Kingdom. The model showed that wet
      deposition was the most important process for the transfer of metals from the
      atmosphere to the land surface. The model achieved a good correlation with
      annually averaged measurements of metal concentrations in air. The correlation
      with measurements of wet deposition was less strong due to the complexity of the
      atmospheric processes involved in the washout of particulate matter which were
      not fully captured by the model. The measured wet deposition and air
      concentration of heavy metals were significantly underestimated by the model for
      all metals (except vanadium) by factors between 2 and 10. These results suggest
      major missing sources of annual heavy metal emissions which are currently not
      included in the official inventory. Primary emissions were able to account for
      only 9%, 21%, 29%, 21%, 36%, 7% and 23% of the measured concentrations for As,
      Cd, Cr, Cu, Ni, Pb and Zn. A likely additional contribution to atmospheric heavy
      metal concentrations is the wind driven re-suspension of surface dust still
      present in the environment from the legacy of much higher historic emissions.
      Inclusion of two independent estimates of emissions from re-suspension in the
      model was found to give an improved agreement with measurements. However, an
      accurate estimate of the magnitude of re-suspended emissions is restricted by the
      lack of measurements of metal concentrations in the re-suspended surface dust
      layer. 

PMID- 24561925
TI  - Soil erodibility in Europe: a high-resolution dataset based on LUCAS.
AB  - The greatest obstacle to soil erosion modelling at larger spatial scales is the
      lack of data on soil characteristics. One key parameter for modelling soil
      erosion is the soil erodibility, expressed as the K-factor in the widely used
      soil erosion model, the Universal Soil Loss Equation (USLE) and its revised
      version (RUSLE). The K-factor, which expresses the susceptibility of a soil to
      erode, is related to soil properties such as organic matter content, soil
      texture, soil structure and permeability. With the Land Use/Cover Area frame
      Survey (LUCAS) soil survey in 2009 a pan-European soil dataset is available for
      the first time, consisting of around 20,000 points across 25 Member States of the
      European Union. The aim of this study is the generation of a harmonised high
      resolution soil erodibility map (with a grid cell size of 500 m) for the 25 EU
      Member States. Soil erodibility was calculated for the LUCAS survey points using
      the nomograph of Wischmeier and Smith (1978). A Cubist regression model was
      applied to correlate spatial data such as latitude, longitude, remotely sensed
      and terrain features in order to develop a high-resolution soil erodibility map.
      The mean K-factor for Europe was estimated at 0.032 thahha(-1)MJ(-1)mm(-1) with a
      standard deviation of 0.009 thahha(-1)MJ(-1)mm(-1). The yielded soil erodibility
      dataset compared well with the published local and regional soil erodibility
      data. However, the incorporation of the protective effect of surface stone cover,
      which is usually not considered for the soil erodibility calculations, resulted
      in an average 15% decrease of the K-factor. The exclusion of this effect in K
      factor calculations is likely to result in an overestimation of soil erosion,
      particularly for the Mediterranean countries, where highest percentages of
      surface stone cover were observed.

PMID- 24561926
TI  - Effects of ambient air pollution on respiratory tract complaints and airway
      inflammation in primary school children.
AB  - Respiratory health effects of ambient air pollution were studied in 605 school
      children 9 to 13 years in Eskisehir, Turkey. Each child performed a fractional
      exhaled nitric oxide (FENO) measurement and a lung function test (LFT). Self
      reported respiratory tract complaints (having cold, complaints of throat, runny
      nose and shortness of breath/wheezing) in the last 7 days and on the day of
      testing were also recorded. As acute health outcomes were investigated, weekly
      average ambient concentrations of ozone (O3), nitrogen dioxide (NO2) and sulfur
      dioxide (SO2) were determined by passive sampling in the school playgrounds
      simultaneously with the health survey. Effects of air pollution on respiratory
      tract complaints and exhaled NO/lung function were estimated by multivariate
      logistic regression and multivariate linear mixed effects models, respectively.
      Upper respiratory tract complaints were significantly (p<0.05) associated with
      weekly average O3 concentrations during the health survey (adjusted odds ratios
      (OR) of 1.21 and 1.28 for a 10 MUgm(-3) increment for having cold and a runny
      nose on day of testing, respectively). FENO levels were significantly (p<0.05)
      increased in children with various upper respiratory tract complaints (ratio in
      FENO varied between 1.16 and 1.40). No significant change in FENO levels was
      detected in association with any of the measured pollutants (p >= 0.05). Lung
      function was not associated with upper respiratory tract complaints and FENO
      levels. Peak Expiratory Flow (PEF) levels were negatively associated with weekly
      average O3 levels for children without upper respiratory tract complaints. In
      summary, elevated levels of air pollutants increased respiratory tract complaints
      in children.

PMID- 24561927
TI  - Assessment of PM2.5 and PM1 chemical profile in a multiple-impacted Mediterranean
      urban area: origin, sources and meteorological dependence.
AB  - Airborne particulate matter in the PM2.5 and PM1 size ranges has been sampled at
      three sites within the Mediterranean urban area of the Athens Basin, representing
      background, roadside-industrialized and coastal background locations. With the
      principal aim to identify the sources and discriminate the contribution of the
      regional input versus the local one, simultaneous chemical characterization with
      respect to carbonaceous and ionic species was also carried out on the collected
      samples. In general, the average recorded values were within the Mediterranean
      concentration range. The constant prevalence of the ionic mass (52%-79%) over one
      of the carbonaceous, being combined with the occurrence of its maximum rates at
      the coastal background environment (74%-79% and 73%-77% for PM2.5 and PM1,
      respectively) leads to the hypothesis that the fine PM pollution in the basin,
      especially for the remote locations, is evidently governed by the external
      intrusion. Even at the polluted atmosphere of the roadside-industrialized
      environment, the PM mass was regionally originated, with the corresponding input
      reaching up to 87% (northward flow). Applying factor analysis on the PM2.5
      database it came obvious that the sources which were responsible for the
      configured PM burden were not fully differentiated not only between the different
      types of environment but also between the exceedances and the clean air events.
      The contribution of the secondary, marine and combustion processes was constant
      at all the stations of the network, while a continuous input of crustal particles
      characterized both the roadside-industrialized and the coastal atmosphere.
      Finally, the episodic values show a general common signal of secondary mixed
      RhoMU emissions, high influence of both regional and local pollution spikes,
      confirming the earlier findings for the significance of transportation. 

PMID- 24561928
TI  - A Bayesian regression approach to assess uncertainty in pollutant wash-off
      modelling.
AB  - Due to knowledge gaps in relation to urban stormwater quality processes, an in
      depth understanding of model uncertainty can enhance decision making. Uncertainty
      in stormwater quality models can originate from a range of sources such as the
      complexity of urban rainfall-runoff-stormwater pollutant processes and the
      paucity of observed data. Unfortunately, studies relating to epistemic
      uncertainty, which arises from the simplification of reality are limited and
      often deemed mostly unquantifiable. This paper presents a statistical modelling
      framework for ascertaining epistemic uncertainty associated with pollutant wash
      off under a regression modelling paradigm using Ordinary Least Squares Regression
      (OLSR) and Weighted Least Squares Regression (WLSR) methods with a Bayesian/Gibbs
      sampling statistical approach. The study results confirmed that WLSR assuming
      probability distributed data provides more realistic uncertainty estimates of the
      observed and predicted wash-off values compared to OLSR modelling. It was also
      noted that the Bayesian/Gibbs sampling approach is superior compared to the most
      commonly adopted classical statistical and deterministic approaches commonly used
      in water quality modelling. The study outcomes confirmed that the predication
      error associated with wash-off replication is relatively higher due to limited
      data availability. The uncertainty analysis also highlighted the variability of
      the wash-off modelling coefficient k as a function of complex physical processes,
      which is primarily influenced by surface characteristics and rainfall intensity. 

PMID- 24561929
TI  - Effect of different oxytetracycline addition methods on its degradation behavior
      in soil.
AB  - The degradation behavior of veterinary antibiotics in soil is commonly studied
      using the following methods of adding antibiotics to the soil: (i) adding manure
      collected from animals fed with a diet containing antibiotics, (ii) adding
      antibiotic-free animal manure spiked with antibiotics and (iii) directly adding
      antibiotics. No research simultaneously comparing different antibiotic addition
      methods was found. Oxytetracycline (OTC) was used as a model antibiotic to
      compare the effect of the three commonly used antibiotic addition methods on OTC
      degradation behavior in soil. The three treatment methods have similar trends,
      though OTC degradation half-lives show the following significant differences
      (P<0.05): manure from swine fed OTC (treatment A)<antibiotic-free manure+OTC
      (treatment B)<OTC (treatment C). Differences could be caused by distinct chemical
      reaction equilibria due to dissimilar concentrations of 4-epi-OTC and alpha-apo
      OTC. The pH could also have affected the concentration of 4-epi-OTC and alpha-apo
      OTC, thus influencing OTC degradation. The treatments presenting manure (A and B)
      significantly enhanced EC, enzyme activity, microbial biomass carbon and nitrogen
      when compared to the treatment without manure (C), thus increasing degradation of
      OTC in the soil. Because the main entry route for veterinary antibiotics into
      soil is via the manure of animals given with antibiotics, the most appropriate
      method to study the degradation and ecotoxicity of antibiotic residues in soil
      may be to use manure from animals that are given a particular antibiotic, rather
      than by adding it directly to the soil. 

PMID- 24561930
TI  - Monitoring of selected priority and emerging contaminants in the Guadalquivir
      River and other related surface waters in the province of Jaen, South East Spain.
AB  - The province of Jaen counts with four natural parks, numerous rivers, reservoirs
      and wetlands; moreover, it is probably the region with higher olive oil
      production in the world, which makes this zone a proper target to be studied
      based on the European Water Framework Directive 2000/60/CE. The aim of this
      survey is to monitor a total number of 373 compounds belonging to different
      families (pesticides, PAHs, nitrosamines, drugs of abuse, pharmaceuticals and
      life-style compounds) in surface waters located at different points of the
      province of Jaen. Among these compounds some priority organic substances
      (regulated by the EU Directive 2008/105/EC) and pollutants of emerging concern
      (not regulated yet) can be found. A liquid chromatography electrospray time-of
      flight mass spectrometry (LC-TOFMS) method covering 340 compounds was developed
      and applied, together with a gas chromatography triple-quadrupole mass
      spectrometry (GC-MS/MS) method which enabled the analysis of 63 organic
      contaminants (30 of these compounds are analyzed by LC-TOFMS as well). From April
      2009 to November 2010 a total of 83 surface water samples were collected (rivers,
      reservoirs and wetlands). In this period numerous organic contaminants were
      detected, most of them at the ng L(-1) level. The most frequently priority
      substances found were chlorpyrifos ethyl, diuron and hexachlorobenzene. Within
      the other groups, the most frequently detected compounds were: terbuthylazine,
      oxyfluorfen, desethyl terbuthylazine, diphenylamine (pesticide family); fluorene,
      phenanthrene, pyrene (PAHs group), codeine, paracetamol (pharmaceuticals
      compounds) and caffeine, nicotine (life-style compounds). As is could be
      expected, the total concentration of emerging contaminants is distinctly larger
      than that of priority pollutants, highlighting the importance of continuing with
      the study of their presence, fate and effects in aquatic environments. However,
      concentration levels (at the ng per liter level) are low in general for both
      kinds of contaminants which minimizes the possible harmful effect on the
      environment.

PMID- 24561932
TI  - Self-training-based face recognition using semi-supervised linear discriminant
      analysis and affinity propagation.
AB  - Face recognition is one of the most important applications of machine learning
      and computer vision. The traditional supervised learning methods require a large
      amount of labeled face images to achieve good performance. In practice, however,
      labeled images are usually scarce while unlabeled ones may be abundant. In this
      paper, we introduce a semi-supervised face recognition method, in which semi
      supervised linear discriminant analysis (SDA) and affinity propagation (AP) are
      integrated into a self-training framework. In particular, SDA is employed to
      compute the face subspace using both labeled and unlabeled images, and AP is used
      to identify the exemplars of different face classes in the subspace. The
      unlabeled data can then be classified according to the exemplars and the newly
      labeled data with the highest confidence are added to the labeled data, and the
      whole procedure iterates until convergence. A series of experiments on four face
      datasets are carried out to evaluate the performance of our algorithm.
      Experimental results illustrate that our algorithm outperforms the other
      unsupervised, semi-supervised, and supervised methods. 

PMID- 24561931
TI  - Sedimentation and associated trace metal enrichment in the riparian zone of the
      Three Gorges Reservoir, China.
AB  - Impoundment of the Three Gorges Reservoir has created an artificial riparian zone
      with a vertical height of 30 m and a total area of 349 km(2), which has been
      subjected to seasonal inundation and exposure due to regular reservoir
      impoundment and the occurrence of natural floods. The significant alteration of
      hydrologic regime has caused numerous environmental changes. The present study
      investigated the magnitude and spatial pattern of sedimentation and metal
      enrichment in a typical section of the riparian zone, composed of bench terraces
      with previous agricultural land uses, and explored their links to the changed
      hydrologic regime. In particular, we measured the total sediment depths and
      collected surface riparian sediments and down-profile sectioned riparian soils
      (at 5 cm intervals) for trace metal determination. Our analysis showed that the
      annual average sedimentation rates varied from 0.5 to 10 cm.yr(-1) and they
      decreased significantly with increasing elevation. This lateral distribution was
      principally attributed to seasonal variations in water levels and suspended
      sediment concentrations. Enriched concentrations of trace metals were found both
      in the riparian sediments and soils, but they were generally higher in the
      riparian sediments than in riparian soils and followed a similar lateral
      decreasing trend. Metal contamination assessment showed that the riparian
      sediments were slightly contaminated by Ni, Zn, and Pb, moderately contaminated
      by Cu, and moderately to strongly contaminated by Cd; while riparian soils were
      slightly contaminated by As, and moderately contaminated by Cd. Trace metal
      enrichment in the riparian sediments may be attributed to external input of
      contaminated sediments produced from upstream anthropogenic sources and chemical
      adsorption from dissolved fractions during pure sediment mobilization and after
      sink for a prolonged flooding period due to reservoir impoundment.

PMID- 24561933
TI  - Effects of dead time and afterpulses in photon detector on measured statistics of
      stochastic radiation.
AB  - Many physical experiments require analysis of the statistics of fluctuating
      radiation. In the case of an ideal single-photon detector, the contribution of
      photon noise to the statistics of the registered signal has been thoroughly
      examined. However, practical photon counters have a dead time, leading to
      miscounting of certain true events, and sometimes the counters generate false
      afterpulses. This study investigates the impact of these two effects, and it
      presents the theoretical relations between the statistical moments of the
      radiation and the registered counts while also accounting for dead time and the
      probability of afterpulses. Expressions for statistical moments of any order are
      obtained on the basis of the generalized Poisson distribution. For counters with
      paralyzable dead time, alternative relations for the mean and variance are
      derived using generally accepted formulas. As an example, the measurements of
      stellar scintillation and the result of a simple experiment are considered. The
      results of the experimental verification of the theoretical expression confirm
      the need to account for the nonideal nature of detectors in almost all similar
      measurements. 

PMID- 24561934
TI  - Speckle reduction in laser imaging applications using rotating magneto-optical
      disk.
AB  - Effective methods for speckle reduction are essential in improving the image
      quality of laser imaging applications. Accordingly, the present study proposes a
      novel technique for reducing the speckle contrast in laser imaging applications
      by means of the magneto-optic Kerr effect induced by a rotating magneto-optical
      (MO) disk. The performance of the proposed method is evaluated experimentally
      using a laboratory-built prototype model. The experimental results show that the
      rotating MO disk can reduce the speckle contrast of the captured image by 60% of
      the previous value. As a result, the proposed method yields an effective
      improvement in image quality. Overall, the proposed method provides a promising
      solution for improving the performance of a wide range of laser imaging
      applications. 

PMID- 24561935
TI  - Diffraction by 90 degrees  penetrable wedges with finite conductivity.
AB  - This study concerns the diffraction problem relevant to a plane wave normally
      incident with respect to a 90 degrees  wedge. A penetrable material with finite
      conductivity forms the structure. A high-frequency solution is here obtained by
      adopting a physical optics approximation for the equivalent electric and magnetic
      surface currents involved in the radiation integrals used to represent the fields
      scattered in the inner region of the wedge and the surrounding space. Uniform
      asymptotic evaluations of such integrals lead to closed form expressions for the
      diffraction coefficient in terms of the transition function of the uniform theory
      of diffraction and the Fresnel coefficients for the reflection and transmission
      mechanisms. No limitation exists on the loss tangent of the medium. Comparisons
      with numerical tools assess the effectiveness of the proposed solutions for the
      field diffracted in the inner and outer regions. 

PMID- 24561936
TI  - Electromagnetic scattering by a circular cylinder buried below a slightly rough
      Gaussian surface.
AB  - A two-dimensional beam is scattered by a cylinder buried below a slightly rough
      surface. The cylindrical wave approach is applied, i.e., cylindrical waves are
      employed as basis functions of the fields scattered by the cylinder. Moreover, a
      spectral representation of both the incident field and the cylindrical waves is
      used. Rough surface deviation is coped with by the first-order small perturbation
      method. Therefore, to a zeroth-order solution relevant to scattering in the case
      of a flat surface, a first-order approximation is superimposed. The theoretical
      approach has been implemented for a periodic surface with Gaussian roughness
      spectrum. 

PMID- 24561937
TI  - Analog-to-digital optical waveguide conversion at sampling periods greater than
      the free-space wavelength.
AB  - Nyquist sampling theorem reveals the possibility of sampling the continuous
      refractive index profiles of optical waveguides at periods greater than the free
      space wavelength, lambda(o). Binary encoding of these analog waveguides is
      investigated using the zero-order effective medium theory, while conserving the
      quantization of the modal spectrum implied by their boundary conditions. Both
      analytical and numerical approaches are developed for this analog-to-digital (A
      to-D) conversion. An example is presented for the A-to-D conversion of a graded
      index waveguide with a hyperbolic secant profile at a sample period of
      1.3lambda(o). The results are confirmed using a beam propagation method.

PMID- 24561938
TI  - Hybrid optoelectronic correlator architecture for shift-invariant target
      recognition.
AB  - In this paper, we present theoretical details and the underlying architecture of
      a hybrid optoelectronic correlator (HOC) that correlates images using spatial
      light modulators (SLMs), detector arrays, and field programmable gate array
      (FPGA). The proposed architecture bypasses the need for nonlinear materials such
      as photorefractive polymer films by using detectors instead, and the phase
      information is yet conserved by the interference of plane waves with the images.
      However, the output of such an HOC has four terms: two convolution signals and
      two cross-correlation signals. By implementing a phase stabilization and scanning
      circuit, the convolution terms can be eliminated, so that the behavior of an HOC
      becomes essentially identical to that of a conventional holographic correlator
      (CHC). To achieve the ultimate speed of such a correlator, we also propose an
      integrated graphic processing unit, which would perform all the electrical
      processes in a parallel manner. The HOC architecture along with the phase
      stabilization technique would thus be as good as a CHC, capable of high-speed
      image recognition in a translation-invariant manner. 

PMID- 24561939
TI  - Reduction or annihilation of aberrations of an optical system by balancing ghost
      imaging technique and optimal imaging of a pure weak phase object.
AB  - It is shown, using ghost-imaging techniques, that it is possible to reduce or
      even to annihilate the influence of aberrations connected with an arbitrary
      optical system. To this end, we consider a ghost-imaging setup, which consists of
      two arms, each containing an optical system. The reduction cancellation of the
      aberrations of the total imaging system is achieved by manipulating the values of
      the aberrations in one arm of the optical system. The technique is then applied
      for the optimal reconstruction of a weak phase object, manipulating the values of
      the defocusing such that the "Scherzer defocus condition" is obtained. 

PMID- 24561940
TI  - Between additive and subtractive color mixings: intermediate mixing models.
AB  - The color rendering of superposed coloring components is often an issue either to
      predict or to simulate the appearance of colored surfaces. In graphical software,
      for example, transparence options are available to display different layouts on
      top of each other. With two colored layers, tuning the transparency of the top
      layer enables transitioning continuously from the color of this top layer to the
      color of the bottom layer. However, these options based very often only on
      additive color mixing offer limited transitions between two base colors. It would
      be advantageous to introduce more advanced options, providing, for example,
      realistic renderings of superposed paint layers. This is the aim of the present
      study, where simple models are proposed to create intermediate configurations
      between additive and subtractive color mixings. These models rely on the spectral
      power distribution of a finite set of primaries with given proportions. They may
      be extended to RGB color reflective or transmissive systems if the red, green,
      and blue wavebands do not overlap each other. An additional parameter is
      introduced to tune the proportions of additive and subtractive mixings, each type
      of mixing being based on its set of primaries. Various simulations of color
      mixings are presented, illustrating the possibilities offered by this model in
      addition to those permitted by the purely additive and subtractive mixings. 

PMID- 24561941
TI  - Singular eigenfunctions for the three-dimensional radiative transport equation.
AB  - Case's method obtains solutions to the radiative transport equation as
      superpositions of elementary solutions when the specific intensity depends on one
      spatial variable. In this paper, we find elementary solutions when the specific
      intensity depends on three spatial variables in three-dimensional space. By using
      the reference frame whose z axis lies in the direction of the wave vector, the
      angular part of each elementary solution becomes the singular eigenfunction for
      the one-dimensional radiative transport equation. Thus, Case's method is
      generalized. 

PMID- 24561942
TI  - Bounding the relative errors associated with a complete Stokes polarimeter.
AB  - In this paper, we propose a criterion for bounding the relative errors associated
      with the determination of the Stokes vector that describes the state of
      polarization of a light beam. No assumptions about the magnitude, origin, or
      statistical behavior of the errors are made. It is shown that figures of merit
      such as the condition number and the equally weighted variance naturally arise as
      optimization parameters. Moreover, a third optimization parameter emerges, which
      takes into account errors associated with the matrix that represents the selected
      configuration of analyzers. Finally, a new and more general figure of merit is
      derived from this analysis and is applied in an optimization process of a very
      well known polarimeter. 

PMID- 24561943
TI  - Residual amplitude modulation in interferometric gravitational wave detectors.
AB  - The effects of residual amplitude modulation (RAM) in laser interferometers using
      heterodyne sensing can be substantial and difficult to mitigate. In this work, we
      analyze the effects of RAM on a complex laser interferometer used for
      gravitational wave detection. The RAM introduces unwanted offsets in the cavity
      length signals and thereby shifts the operating point of the optical cavities
      from the nominal point via feedback control. This shift causes variations in the
      sensing matrix, and leads to degradation in the performance of the precision
      noise subtraction scheme of the multiple-degree-of-freedom control system. In
      addition, such detuned optical cavities produce an optomechanical spring, which
      also perturbs the sensing matrix. We use our simulations to derive requirements
      on RAM for the Advanced LIGO (aLIGO) detectors, and show that the RAM expected in
      aLIGO will not limit its sensitivity. 

PMID- 24561944
TI  - Scattering of an electromagnetic plane wave by a homogeneous sphere made of an
      orthorhombic dielectric-magnetic material.
AB  - An exact transition matrix was formulated for electromagnetic scattering by an
      orthorhombic dielectric-magnetic sphere whose permeability dyadic is a scalar
      multiple of its permittivity dyadic. Calculations were made for plane waves
      incident on the sphere. As the size parameter increases, the role of anisotropy
      evolves; multiple lobes appear in the plots of the differential scattering
      efficiency in any scattering plane; the total scattering, extinction, and forward
      scattering efficiencies exhibit a prominent maximum each; and the absorption
      efficiency generally increases with weak undulations. Certain orientations of the
      sphere with respect to the directions of propagation and the electric field of
      the incident plane wave make it highly susceptible to detection in a monostatic
      configuration, whereas other orientations make it much less vulnerable to
      detection. Impedance match to the ambient free space decreases backscattering
      efficiency significantly, although anisotropy prevents null backscattering. 

PMID- 24561945
TI  - Static and predictive tomographic reconstruction for wide-field multi-object
      adaptive optics systems.
AB  - Multi-object adaptive optics (MOAO) systems are still in their infancy: their
      complex optical designs for tomographic, wide-field wavefront sensing, coupled
      with open-loop (OL) correction, make their calibration a challenge. The
      correction of a discrete number of specific directions in the field allows for
      streamlined application of a general class of spatio-angular algorithms,
      initially proposed in Whiteley et al. [J. Opt. Soc. Am. A15, 2097 (1998)], which
      is compatible with partial on-line calibration. The recent Learn & Apply
      algorithm from Vidal et al. [J. Opt. Soc. Am. A27, A253 (2010)] can then be
      reinterpreted in a broader framework of tomographic algorithms and is shown to be
      a special case that exploits the particulars of OL and aperture-plane phase
      conjugation. An extension to embed a temporal prediction step to tackle sky
      coverage limitations is discussed. The trade-off between lengthening the camera
      integration period, therefore increasing system lag error, and the resulting
      improvement in SNR can be shifted to higher guide-star magnitudes by introducing
      temporal prediction. The derivation of the optimal predictor and a comparison to
      suboptimal autoregressive models is provided using temporal structure functions.
      It is shown using end-to-end simulations of Raven, the MOAO science, and
      technology demonstrator for the 8 m Subaru telescope that prediction allows by
      itself the use of 1-magnitude-fainter guide stars. 

PMID- 24561946
TI  - Estimating the eye aberration coefficients in resized pupils: is it better to
      refit or to rescale?
AB  - In order to work in a consistent way with Zernike aberration coefficients
      estimated in different pupils, it is necessary to refer them to a common pupil
      size. Two standard approaches can be used to that end: to rescale algebraically
      the coefficients estimated in the original pupil or to refit them anew using the
      wavefront slope measurements available within the new one. These procedures are
      not equivalent; they are affected by different estimation errors that we address
      in this work. Our results for normal eye populations show that in case of
      reducing the pupil size it is better to rescale the original coefficients than to
      refit them using the measurements contained within the smaller pupil. In case of
      enlarging the pupil size, as it can a priori be expected, the opposite holds
      true. We provide explicit expressions to quantify the errors arising in both
      cases, including the expected error incurred when extrapolating the Zernike
      estimation beyond the radius where the measurements were made. 

PMID- 24561947
TI  - High-precision and fast computation of Jacobi-Fourier moments for image
      description.
AB  - A high-precision and fast algorithm for computation of Jacobi-Fourier moments
      (JFMs) is presented. A fast recursive method is developed for the radial
      polynomials that occur in the kernel function of the JFMs. The proposed method is
      numerically stable and very fast in comparison with the conventional direct
      method. Moreover, the algorithm is suitable for computation of the JFMs of the
      highest orders. The JFMs are generic expressions to generate orthogonal moments
      changing the parameters alpha and beta of Jacobi polynomials. The quality of the
      description of the proposed method with alpha and beta parameters known is
      studied. Also, a search is performed of the best parameters, alpha and beta,
      which significantly improves the quality of the reconstructed image and
      recognition. Experiments are performed on standard test images with various sets
      of JFMs to prove the superiority of the proposed method in comparison with the
      direct method. Furthermore, the proposed method is compared with other existing
      methods in terms of speed and accuracy. 

PMID- 24561948
TI  - Discrete-dipole approximation on a rectangular cuboidal point lattice:
      considering dynamic depolarization.
AB  - Discrete-dipole approximation (DDA), which is used for computing scattering and
      absorption by particles of arbitrary geometry and material, is extended to the
      case of a rectangular cuboidal point lattice using an accurate, analytical
      expression of the polarizability of each cuboidal element at optical frequencies
      of up to 100 nm in size. This polarizability formulation (cuboidal lattice with
      depolarization or CLD) is shown to be more accurate in the computation of the
      extinction, scattering, and absorption cross sections when simulating dielectrics
      compared to other available and commonly used expressions of the polarizability.
      This can be used to reduce the number of dipoles N used, and therefore, the
      computation time while achieving the same accuracy of other formulations. The CLD
      formulation was applied to the Mie scattering problem and the results were
      compared to results from other DDA formulations, as well as to the Mie analytical
      solution for metal and dielectric spheres. Metal cubes were also simulated and
      different formulations compared. 

PMID- 24561949
TI  - Modified fundamental Airy wave.
AB  - The propagation characteristics of the fundamental Airy wave are obtained; the
      intensity distribution is the same as that for a point electric dipole situated
      at the origin and oriented normal to the propagation direction. The propagation
      characteristics of the modified fundamental Airy wave are determined. These
      characteristics are the same as those for the fundamental Gaussian wave provided
      that an equivalent waist is identified for the Airy wave. In general, the waves
      are localized spatially with the peak in the propagation direction. 

PMID- 24561950
TI  - Analytical expressions for the log-amplitude correlation function for spherical
      wave propagation through anisotropic non-Kolmogorov atmosphere.
AB  - An analytical expression for the log-amplitude correlation function based on the
      Rytov approximation is derived for spherical wave propagation through an
      anisotropic non-Kolmogorov refractive turbulent atmosphere. The expression
      reduces correctly to the previously published analytic expressions for the case
      of spherical wave propagation through isotropic Kolmogorov turbulence. These
      results agree well with a wave-optics simulation based on the more general
      Fresnel approximation, as well as with numerical evaluations, for low-to-moderate
      strengths of turbulence. These results are useful for understanding the potential
      impact of deviations from the standard isotropic Kolmogorov spectrum. 

PMID- 24561951
TI  - Plasmon-based tomographic microscopy.
AB  - The imaging principle of the scanning surface plasmon microscope (SSPM) springs
      from the high sensitivity of surface plasmons to modifications of material
      properties near the dielectric-metal interface. In this paper, we show that
      tomographic techniques can be applied to SSPM imaging of dielectric objects to
      reach resolutions beyond the diffraction-limited half-wavelength scale.
      Furthermore, this high resolution is not limited to the multiple scattering
      regime. Finally, we conclude that SSPM is less sensitive to noise because it
      provides higher contrast ratio than other far-field microscopies. 

PMID- 24561952
TI  - Surface scattering of core-shell particles with anisotropic shell.
AB  - The Bobbert-Vlieger solution to light scattering of a spherical particle
      suspended above a surface is extended to model the scattering of core-shell
      structures with anisotropic shell. Numerical modeling demonstrates that
      ellipsometry has potential to resolve particle shell anisotropy down to 1.8*10(
      4) for SiO(2)@Au core-shell particles in air with 50 nm core diameter and 10 nm
      shell thickness deposited on a silicon Si [100] substrate with a density of 1 
      MUm(-2). Application of the Ibrahim and Bashara criterion for ellipsometer
      parameter cross correlation identifies variable-angle ellipsometry as a viable
      experimental approach to separate particle core radius and shell thickness from
      the shell anisotropy. Ellipsometry is also identified as an alternative technique
      for determination of liposome anisotropy and for the study of liposome fusion
      with a substrate in the formation process of supported lipid bilayers.

PMID- 24561953
TI  - Propagation characteristics of decentered annular beams through non-Kolmogorov
      turbulence.
AB  - This paper studies the propagation characteristics related to higher-order
      moments of decentered annular beams through non-Kolmogorov turbulence. The
      analytical expressions for the mean-squared beam width w, the skewness parameter
      A, and the kurtosis parameter K are derived. The analytical expression for the
      non-Kolmogorov turbulence parameter T' is also derived, and the differences
      between two non-Kolmogorov turbulence parameters T' and T are examined. It is
      shown that K depends on both T and T', but w and A only depend on T. K decreases
      monotonically as the spectral power law exponent alpha increases, but there exist
      a maximum of w and a minimum of A when alpha=3.112. When propagation distance z
      is long enough, A reaches zero, i.e., the intensity distribution is perfectly
      symmetric about the centroid position axis. In free space, both A>0 and A<0 may
      appear on propagation. However, it is always A>0 or A<0 on propagation when
      turbulence is not weak. On the other hand, in turbulence, the maximum of K
      increases as the decentered parameter increases and the obscure ratio decreases.
      In particular, when z is long enough, the beam spot is elliptical in free space,
      but it becomes circular in turbulence.

PMID- 24561954
TI  - Real-time pseudocolor coding thermal ghost imaging.
AB  - In this work, a color ghost image of a black-and-white object is obtained by a
      real-time pseudocolor coding technique that includes equal spatial frequency
      pseudocolor coding and equal density pseudocolor coding. This method makes the
      black-and-white ghost image more conducive to observation. Furthermore, since the
      ghost imaging comes from the intensity cross-correlations of the two beams, ghost
      imaging with the real-time pseudocolor coding technique is better than classical
      optical imaging with the same technique in overcoming the effects of light
      interference. 

PMID- 24561955
TI  - Abundant soliton solutions of general nonlocal nonlinear Schrodinger system with
      external field.
AB  - Periodic and quasi-periodic breather multi-solitons solutions, the dipole-type
      breather soliton solution, the rogue wave solution, and the fission soliton
      solution of the general nonlocal Schrodinger equation are derived by using the
      similarity transformation and manipulating the external potential function. The
      stability of the exact solitary wave solutions with the white noise perturbation
      also is investigated numerically. 

PMID- 24561956
TI  - Defect detection of castings in radiography images using a robust statistical
      feature.
AB  - One of the most commonly used optical methods for defect detection is
      radiographic inspection. Compared with methods that extract defects directly from
      the radiography image, model-based methods deal with the case of an object with
      complex structure well. However, detection of small low-contrast defects in
      nonuniformly illuminated images is still a major challenge for them. In this
      paper, we present a new method based on the grayscale arranging pairs (GAP)
      feature to detect casting defects in radiography images automatically. First, a
      model is built using pixel pairs with a stable intensity relationship based on
      the GAP feature from previously acquired images. Second, defects can be extracted
      by comparing the difference of intensity-difference signs between the input image
      and the model statistically. The robustness of the proposed method to noise and
      illumination variations has been verified on casting radioscopic images with
      defects. The experimental results showed that the average computation time of the
      proposed method in the testing stage is 28 ms per image on a computer with a
      Pentium Core 2 Duo 3.00 GHz processor. For the comparison, we also evaluated the
      performance of the proposed method as well as that of the mixture-of-Gaussian
      based and crossing line profile methods. The proposed method achieved 2.7% and
      2.0% false negative rates in the noise and illumination variation experiments,
      respectively. 

PMID- 24561957
TI  - Optical binding of cylinder photonic molecules in the near field of partially
      coherent fluctuating Gaussian Schell model sources: a coherent mode
      representation.
AB  - We present a theory and computation method of radiation pressure from partially
      coherent light by establishing a coherent mode representation of the radiation
      forces. This is illustrated with the near field emitted from a Gaussian Schell
      model source, mechanically acting on a single cylinder with magnetodielectric
      behavior, or on a photonic molecule constituted by a pair of such cylinders. Thus
      after studying the force produced by a single particle, we address the effects of
      the spatial coherence on the bonding and antibonding states of two particles. The
      coherence length manifests the critical limitation of the contribution of
      evanescent modes to the scattered fields, and hence to the nature and strength of
      the electromagnetic forces, even when electric and/or magnetic partial wave
      resonances are excited. 

PMID- 24561958
TI  - Journal of the Optical Society of America a 30th Anniversary: editorial.
AB  - Journal of the Optical Society of America A Editor-in-Chief, Franco Gori,
      announces the 30th Anniversary of the journal.

PMID- 24561959
TI  - Virus adsorption of water-stable quaternized chitosan nanofibers.
AB  - The burden of unsafe drinking water is responsible for millions of deaths each
      year. To relieve this burden, we are in search of an inexpensive material that
      can adsorb pathogens from drinking water. In this pursuit, we have studied the
      natural carbohydrate, chitosan. To impart virus removal features, chitosan has
      been functionalized with a quaternary amine to form quaternized chitosan N-[(2
      hydroxyl-3-trimethylammonium) propyl] chitosan (HTCC). HTCC can be electrospun
      into nanofibers with the non-ionogenic polyvinyl alcohol (PVA), creating a high
      surface area mat. High surface area is a major requirement for effective
      adsorption processes. HTCC is antiviral and antimicrobial, making it a good
      material for water purification. However, HTCC dissolves in water. We have
      explored the parameters to crosslink the nanofibers with glutaraldehyde. We have
      imparted water stability so there is a maximum of 30% swelling of the fibers
      after 6h in water. The water stable fibers retain their ability to adsorb virus,
      as shown for an enveloped and nonenveloped virus. HTCC now has the potential to
      be incorporated into a microfiltration membrane that can remove viruses. This
      could create an inexpensive, low pressure filtration membrane for drinking water
      purification. 

PMID- 24561960
TI  - Angular dependence of the magnetoresistance effect in a silicon based p-n
      junction device.
AB  - We report a pronounced angular dependence of the magnetoresistance (MR) effect in
      a silicon based p-n junction device at room temperature by manipulating the space
      charge region of the p-n junction under a magnetic field. For the p-n junction
      device with various space charge region configurations, we find that all the
      angular dependence of the MR effect is proportional to sin(2)(theta), where the
      theta is the angle between the magnetic field and the driving current. With
      increasing the magnetic field and driving current, the anisotropic MR effect is
      obviously improved. At room temperature, under a magnetic field 2 T and driving
      current 20 mA, the MR ratio is about 50%, almost one order of amplitude larger
      than that in the magnetic material permalloy. Our results reveal an
      interpretation of the MR effect in the non-magnetic p-n junction in terms of the
      Lorentz force and give a new way for the development of future magnetic sensors
      with non-magnetic p-n junctions. 

PMID- 24561961
TI  - Utility of hard exudates for the screening of macular edema.
AB  - PURPOSE: The purpose of this study was to determine whether hard exudates (HEs)
      within one disc diameter of the foveola is an acceptable criterion for the
      referral of diabetic patients suspected of clinically significant macular edema
      (CSME) in a screening setting. METHODS: One hundred forty-three adults diagnosed
      as having diabetes mellitus were imaged using a nonmydriatic digital fundus
      camera at the Alameda County Medical Center in Oakland, CA. Nonstereo fundus
      images were graded independently for the presence of HE near the center of the
      macula by two graders according to the EyePACS grading protocol. The patients
      also received a dilated fundus examination on a separate visit. Clinically
      significant macular edema was determined during the dilated fundus examination
      using the criteria set forth by the Early Treatment Diabetic Retinopathy Study.
      Subsequently, the sensitivity and specificity of HEs within one disc diameter of
      the foveola in nonstereo digital images used as a surrogate for the detection of
      CSME diagnosed by live fundus examination were calculated. RESULTS: The mean (+/
      SD) age of 103 patients included in the analysis was 56 +/- 17 years. Clinically
      significant macular edema was diagnosed in 15.5% of eyes during the dilated
      examination. For the right eyes, the sensitivity of HEs within one disc diameter
      from the foveola as a surrogate for detecting CSME was 93.8% for each of the
      graders; the specificity values were 88.5 and 85.1%. For the left eyes, the
      sensitivity values were 93.8 and 75% for each of the two graders, respectively;
      the specificity was 87.4% for both graders. CONCLUSIONS: This study supports the
      use of HE within a disc diameter of the center of the macula in nonstereo digital
      images for CSME detection in a screening setting.

PMID- 24561962
TI  - Spectacles may improve reading speed in children with hyperopia.
AB  - PURPOSE: The purpose of this study was to investigate the role of (hyperopic or
      myopic) spectacle correction in reading speed of 9- to 10-year-old children.
      METHODS: Subjects were recruited at their schools. Initial selection was based on
      reduced distance acuity and/or a positive blur test. Final inclusion depended on
      cycloplegic refraction. Forty-three myopes were prescribed glasses. Sixty-five
      hyperopes were randomized to three groups: (1) no glasses, (2) +0.5DS for both
      eyes, and (3) full correction. Before and 4 to 6 months after prescription of
      glasses, reading speed was tested: One-Minute Test (reading speed of genuine
      words) and the Klepel (reading speed of nonwords). Data for this second reading
      test were obtained in 34 myopes and 48 hyperopes. RESULTS: At baseline, myopes
      had about 11% higher One-Minute scores (p = 0.005) and about 9% higher Klepel
      scores (p = 0.066) than hyperopes. At follow-up, the hyperopia-full correction
      group improved its One-Minute score by about 13% more than both the no-glasses
      group (p = 0.012) and +0.5DS group (p = 0.019). Spectacles did not, or only
      slightly, improve reading scores of myopes (One-Minute scores, p = 0.068; Klepel
      scores, p = 0.021). CONCLUSIONS: Correction of hyperopia may increase speed of
      reading (as reflected by the One-Minute score). The fact that reading speed of
      nonwords does not increase after correction suggests that hyperopia affects speed
      of recognition but not decoding per se.

PMID- 24561963
TI  - Letter to the editor: Bright light induces choroidal thickening in chickens.

PMID- 24561964
TI  - Authors' response.

PMID- 24561965
TI  - Placental alkaline phosphatase positivity in metastatic melanoma.

PMID- 24561966
TI  - Phycocyanobilin in solution--a solvent triggered molecular switch.
AB  - We present a computational investigation of the conformational response of
      phycocyanobilin (PCB) to the ability of solvents to form hydrogen bonds. PCB is
      the chromophore of several proteins in light harvesting complexes. We determine
      the conformational distributions in different solvents (methanol and
      hexamethylphosphoramide HMPT) by means of ab initio molecular dynamics
      simulations and characterize them via ab initio calculations of NMR chemical
      shift patterns. The computed trajectories and spectroscopic fingerprints
      illustrate that the energy landscape is very complex and exhibits various
      conformations of similar energy. We elucidate the strong influence of the solvent
      characteristics on the structural and spectroscopic parameters. Specifically, we
      predict a cis-trans isomerization of phycocyanobilin upon switching from the
      aprotic to the protic solvent, which explains an experimentally observed change
      in the NMR patterns. In the context of technological molecular recognition,
      solvent induced conformational switching can be considered a precursor mechanism
      to the recognition of single molecules. 

PMID- 24561967
TI  - Ecosystem Health Disorders - changing perspectives in clinical medicine and
      nutrition.
AB  - The inseparability of people from their ecosystem without biological change is
      increasingly clear. The discrete species concept is becoming more an
      approximation as the interconnectedness of all things, animate and inanimate,
      becomes more apparent. Yet this was evident even to our earliest Homo Sapiens
      sapiens ancestors as they hunted and gathered from one locality to another and
      migrated across the globe. During a rather short 150-200,000 years of ancestral
      history, we have changed the aeons-old planet and our ecology with dubious
      sustainability. As we have changed the ecosystems of which we are a part, with
      their opportunities for shelter, rest, ambulation, discourse, food, recreation
      and their sensory inputs, we have changed our shared biology and our health
      prospects. The rate of ecosystem change has increased quantitatively and
      qualitatively and so will that of our health patterns, depending on our
      resilience and how linear, non-linear or fractal-like the linkage. Our health
      associated ecosystem trajectories are uncertain. The interfaces between us and
      our environment are blurred, but comprise time, biorhythms, prokaryotic
      organisms, sensory (auditory, visual, tactile, taste and smell), conjoint
      movement, endocrine with various external hormonal through food and contaminants,
      the reflection of soil and rock composition in the microbes, plants, insects and
      animals that we eat (our biogeology) and much more. We have sought ways to
      optimise our health through highly anthropocentric means, which have proven
      inadequate. Accumulated ecosystem change may now overwhelm our health. On these
      accounts, more integrative approaches and partnerships for health care practice
      are required. 

PMID- 24561968
TI  - Dietetics in China at the crossroads.
AB  - BACKGROUND: A dietetics profession that conforms to the international standards
      for dietetics exists in many countries but not in the Peoples' Republic of China
      (China). Might China benefit from the presence of the dietetics profession?
      OBJECTIVE: The article reviews the current dietetic situation in China,
      summarizes the gaps between current realities in China with respect to meeting
      needs for nutritional care, and recommends improvements. RESULTS: Gaps and
      barriers exist between current practice in dietetics and a more optimal system
      for meeting China's nutritional care needs. Recommendations for actions over the
      near term that would lead to fuller development of the field of dietetics in
      China are summarized, following the model suggested by the International
      Confederation of Dietetic Associations. Alternative personnel deployment
      strategies over the next decade are also discussed. CONCLUSION: Whether there is
      a role for the profession of dietetics in China today or in the near future will
      depend on the attitudes and political will of Chinese government authorities,
      health professionals, educators, and consumers.

PMID- 24561969
TI  - Nutritional standards for energy-dense low-nutrient density foods for children in
      Korea.
AB  - The increasing rate of child obesity has developed into a serious concern in
      contemporary society. In Korea, additional concerns over unsanitary environments
      of food establishments near schools led to the enforcement in 2009 of the Special
      Act on the Safety Management of Children's Dietary Life in order to improve food
      safety and nutrition. Some of the main policies of the Special Act are the
      prohibition of Energy- dense Low-Nutrient density Foods (hereinafter referred to
      as EDLNF) at school canteens and in the outstanding businesses, along with
      restrictions on television advertisement for EDLNF products. Confectioneries,
      candies, sweetened-ice products, breads, chocolates, processed milk, fermented
      milk, ice cream, fish-meat sausages, fruit/vegetable beverages, carbonated
      beverages, mixed beverages, and lactic acid bacteria beverages are classified as
      applicable food types of EDLNF. To establish the nutritional standards for EDLNF,
      the intake proportions and the pattern of nutrients in children's preferred foods
      in Korea were analyzed, based on the 2005 National Health and Nutrition Survey of
      Korea. The foods containing more than 250 kcal, more than 17 g of sugar or more
      than 4 g of saturated fat and less than 2 g of protein per serving are considered
      EDLNF snacks. The Korean government is concentrating its efforts in promoting
      healthy environments for children in its research and in food policies. Further
      studies are necessary to investigate the current state of changes in the
      children's foods industry. 

PMID- 24561970
TI  - The effects of intravenous, enteral and combined administration of glutamine on
      malnutrition in sepsis: a randomized clinical trial.
AB  - Our aim was to compare the effects of intravenous, enteral, and enteral plus
      intravenous supplemented glutamine on plasma transferrin, nitrogen balance, and
      creatinine/height index in septic patients with malnutrition. Blood and urine
      samples were collected for transferrin, urea and creatinine measurements.
      Samples, SOFA score and protein-calorie intake values were repeated on days 7 and
      15. Patients (n:120) were randomly divided into 4 groups. Group I received 30
      g/day IV glutamine, group II received 30 g/day enteral glutamine, group III
      received 15 g/day IV and 15 g/day enteral glutamine. Group IV received only
      enteral feeding as a control group. Transferrin levels decreased in group IV
      (p<0.01 0-7 days, p<0.01 7-15 days, p<0.01 0-15 days). Nitrogen balance levels
      were highest in group IV when compared with group I (p<0.05, p<0.001), group II
      (p<0.001), and group III (p<0.05, p<0.001) on days 7-15. Creatinine/height
      indexes increased in group I (p<0.001), group II (p<0.001), group III (p<0.001),
      and group IV (p<0.05) on day 15. In group III the creatinine/height index was
      higher than in groups I and II (p<0.05). In group IV, creatinine/height index was
      lower than in group I (p<0.01) and group II (p<0.001). Protein-calorie intake in
      group IV was higher than others on day 7 (p<0.05). SOFA scores of group IV were
      higher than the other groups on day 15 (p<0.05). This study demonstrated, that
      combined route of gln supplementation resulted in the most positive outcome to
      transferrin, creatine/height index and nitrogen balance (on days 7 and 15) during
      the catabolic phase of septic patients with malnutrition. 

PMID- 24561971
TI  - Fast-track improves post-operative nutrition and outcomes of colorectal surgery:
      a single-center prospective trial in China.
AB  - Fast-track (FT) has been shown to enhance post-operative recovery. The aim of
      this study was to compare the effects of FT and traditional nutrition on post
      operative rehabilitation, as well as evaluate the feasibility of applying FT in
      nutrition management of colorectal surgery. A prospective and randomized
      controlled trial was performed. This study included 464 patients who underwent
      colorectal surgery. The patients were randomly assigned into an FT group and a
      traditional group. The nutritional risk screening (NRS 2002) score, post
      operative recovery index and surgical complications were compared between the FT
      and traditional groups. The NRS 2002 score in the FT group was better than the
      traditional group (p<0.05). Serum indicators for nutrition (HGB, ALB, A/G) and
      immune function (lymphocyte rate [LYMPH%], IgA, and CD4+) in the FT group were
      superior to those in the traditional group (p<0.05) on post-operative day 5. The
      first time to aerofluxus, defecation, oral intake and ambulation in the FT group
      was shorter when compared to the traditional group (p<0.05). The complication
      incidence was significantly lower in the FT group than in the traditional group
      (p<0.05). In particular, the occurrence rate of anastomotic leakage was higher in
      the traditional group than in the FT group (0.5% vs 2.8%, p<0.05). Taken
      together, these data suggest that FT management can improve the nutritional
      condition and outcomes of colorectal surgical patients. 

PMID- 24561973
TI  - Association of dietary fatty acids intake with pro-coagulation and inflammation
      in Saudi Adults.
AB  - The aim of the study was to understand whether dietary fatty acids such as
      saturated, polyunsaturated, and monounsaturated fatty acids act as inflammatory
      mediators or influence pro-coagulation in Saudi adults. The study sought to
      examine inflammatory factors such as C-reactive protein, tumor necrosis factor
      alpha and activated plasminogen activator inhibitor 1. A total number of 232
      consenting Saudi adults, aged 18-60 years were randomly selected in this cross
      sectional study. Independent Student t-test was done to compare means of normally
      distributed data. Spearman correlation between the variables was determined. The
      values of different fatty acids and adipokines were transformed
      logarithmically/square root to normalize data before correlations were determined
      and statistical analyses performed. Statistical significance was set at p<0.05.
      The results show a significant positive correlation of dietary intake of poly and
      monounsaturated fatty acids, but not saturated fatty acids, with activated
      plasminogen activator inhibitor 1 (r=0.31, p=0.02, r=0.32 p=0.04). On the other
      hand, dietary intake of saturated fatty acids showed a negative correlation with
      serum C-reactive protein levels (p=0.001) in males. Dietary unsaturated fatty
      acids is possibly associated with the production of a pro-coagulation factor
      without enhancing the secretion of pro-inflammatory molecules, while saturated
      fatty acids have no effect on activated plasminogen activator inhibitor 1, but
      their level is negatively associated with the inflammatory factor C-reactive
      protein. We conclude that dietary intake may exert a gender-specific effect in
      inflammatory processes among adults. Further studies are warranted to confirm
      present findings. 

PMID- 24561974
TI  - Association between body fat and vitamin D status in Korean adults.
AB  - The relationship between body fat mass and vitamin D appears to vary by
      ethnicity, but our understanding of this predisposition in Asians is limited due
      to the scarcity of prior investigations. Data on 1,697 Korean adults were
      obtained from the second and third years (2008-2009) of the fourth Korean
      National Health and Nutritional Examination Survey. Body fat mass was measured
      using dual-energy X-ray absorptiometry. Both linear regression analysis for serum
      25-hydroxyvitamin D [25(OH)D] and logistic analysis for vitamin D deficiency
      [25(OH)D <20 ng/mL] were performed to determine significant predictors among BMI,
      waist circumference (WC), and body fat percentage (BF), after adjustment of
      multiple covariates. To explore a possible non-linear relationship between them,
      the fractional polynomials method was used. All analyses were conducted following
      stratification by sex. In linear regression analysis, BMI and WC were not
      associated with 25(OH)D. However, BF was inversely related to 25(OH)D,
      irrespective of the fat location (both appendicular and truncal fat) in both
      sexes. In logistic regression analysis, the highest quartile group of BF had a
      greater OR for vitamin D deficiency than the lower quartile groups, irrespective
      of the fat location and sex. However, the quartiles of BMI and WC were not
      associated with vitamin D deficiency. The linear relationships between BF and
      25(OH)D (or vitamin D deficiency) were confirmed despite use of the fractional
      polynomials method. Body fat mass is inversely associated with serum 25(OH)D in
      Korean adults. Monitoring of vitamin D deficiency in Korean adults with high fat
      mass is needed. 

PMID- 24561975
TI  - Eating behaviors and weight over time in a prospective study: the Healthy Twin
      Study.
AB  - We examined the relationships of combined initial restrained and
      external/emotional eating with initial BMI and change in weight and these
      subscales over time. BMI and the Dutch Eating Behavior Questionnaire were
      twicemeasured in 1361 Korean twins and families (482 men, 879 women) over a
      period of 2.7+/-0.9 years. Subjects were classified by combination of initial sex
      specific restrained and external (or emotional) eating tertiles. Linear mixed
      models were performed after adjusting for confounders at baseline (household,
      sibling relations, sex, age, education level, smoking, alcohol use, energy
      intake, physical activity, and medical history). In adjusted models, initial BMI
      increased with increasing tertiles of initial restrained eating across initial
      external/emotional eating tertiles. Weight was less likely to increase over time
      with increasing tertiles of initial restrained eating in the lowest external
      eating tertile and middle tertile of emotional eating at baseline. Subscale
      scores decreased over time with increasing tertiles of corresponding subscales at
      baseline. These findings suggest that high dietary restraint and
      external/emotional eating may indicate concurrent high BMI and attenuated weight
      gain and decreases in corresponding subscales over time. 

PMID- 24561972
TI  - A school-based comprehensive lifestyle intervention among Chinese kids against
      Obesity (CLICK-Obesity) in Nanjing City, China: the baseline data.
AB  - BACKGROUND: urgent development of effective interventions to prevent rapidly
      rising childhood obesity in China is needed. METHODS: Between May 2010 and
      December 2013, a cluster randomized controlled trial was conducted among 4th
      graders in eight urban primary schools randomly assigned to intervention or
      control groups in Nanjing, China. A multi-component intervention program was
      implemented within the treatment group, while students in the control group
      followed their usual health education curriculum without additional intervention.
      RESULTS: At baseline, 638 and 544 students were enrolled in the intervention and
      control group, respectively. The prevalence of excess body weight was 26.8%, with
      27.4% in the intervention group and 26.1% in the control group (p=0.61). The mean
      (SD) BMI and WC was 18.7 (3.0) and 63.0 (9.2) for participants in intervention
      schools, and 18.5 (2.9) and 63.6 (8.7) for students in control group, separately
      (p=0.24 and 0.41, respectively). Compared to those who were not aware of what
      lifestyle/behavior factors were unhealthy, students who were aware of the
      unhealthy lifestyle/ behavior factors consumed fewer fried snacks (0.46+/-0.76
      serves/week vs 0.65+/-0.91 serves/week; p<0.01), soft drinks (160+/-194 ml/week
      vs 199+/-227 ml/week; p<0.01), but larger amount of meat (502+/-429 g/week vs
      449+/-344 g/week; p=0.03), and reported less screen time (214+/-232 minutes/week
      vs 252+/-264 minutes/week; p<0.01). Moreover, there was no difference within
      physical activity time between these two groups (257+/-341 minutes/week vs 218+/
      324 minutes/week; p=0.13). CONCLUSIONS: Main characteristics of participants were
      balanced at baseline within intervention and control schools, but a gap existed
      between healthy lifestyle knowledge and actual healthy behavior in students.
      TRIAL REGISTRATION NUMBER: ChiCTR-ERC-11001819.

PMID- 24561976
TI  - Sleep deprivation is related to obesity and low intake of energy and
      carbohydrates among working Iranian adults: a cross sectional study.
AB  - Sleep deficiency is becoming widespread in both adults and adolescents and is
      accompanied by certain behaviors that can lead to obesity. This study aims to
      investigate differences in sleep duration of overweight/obese and normal weight
      groups, and the association between sleep deprivation and obesity, dietary intake
      and physical activity. A cross-sectional study was conducted among 226 Iranian
      working adults (109 men and 117 women) aged 20 to 55 years old who live in
      Tehran. Body weight, height, waist and hip circumferences were measured, and BMI
      was calculated. Questionnaires, including the Sleep Habit Heart Questionnaire
      (SHHQ), International Physical Activity Questionnaire (IPAQ) and 24-hour dietary
      recall, were interview-administered. Subjects were categorized as normal weight
      (36.3%) or overweight/obese (63.7%) based on WHO standards (2000). Overweight/
      obese subjects slept significantly (p<0.001) later (00:32+/-00:62 AM) and had
      shorter sleep duration (5.37+/-1.1 hours) than normal weight subjects (23:30+/
      00:47 PM and 6.54+/-1.06 hours, respectively). Sleep duration showed significant
      (p<0.05) direct correlations to energy (r = 0.174), carbohydrate (r = 0.154) and
      fat intake (r = 0.141). This study revealed that each hour later in bedtime
      (going to bed later) increased the odds of being overweight or obese by 2.59-fold
      (95% CI: 1.61-4.16). The findings in this study confirm that people with shorter
      sleep duration are more likely to be overweight or obese; hence, strategies for
      the management of obesity should incorporate a consideration of sleep patterns. 

PMID- 24561977
TI  - Socio-economic factors and use of maternal health services are associated with
      delayed initiation and non-exclusive breastfeeding in Indonesia: secondary
      analysis of Indonesia Demographic and Health Surveys 2002/2003 and 2007.
AB  - This analysis aims to examine factors associated with delayed initiation and non
      exclusive breastfeeding in Indonesia. Data were derived from the 2002/2003 and
      2007 Indonesia Demographic and Health Survey. Information from 12,191 singleton
      live-born infants aged 0-23 months was used to examine factors associated with
      delayed initiation of breastfeeding. Furthermore, information from 3,187
      singleton live-born infants aged 0-5 months was used to identify factors
      associated with non-exclusive breastfeeding. Associations between potential
      predictors and study outcomes were examined using logistic regression. Our study
      found that infants from high household wealth-index had significantly increased
      odds of both delayed initiation and non-exclusive breastfeeding. Other factors
      associated with an increased odds of delayed initiation of breastfeeding included
      infants from Sumatera region (OR=1.64, 95% CI: 1.38-1.95), Caesarean-section
      deliveries (OR=1.84, 95% CI: 1.39-2.44) and deliveries in government-owned
      (OR=1.38, 95% CI: 1.08-1.76) and non-health facility (OR=1.20, 95% CI: 1.00
      1.43). Other factors associated with an increased odds for non-exclusive
      breastfeeding included parents who were in the workforce (OR=1.37, 95% CI: 1.06
      1.78) and mothers with obstetric complication at childbirth (OR=1.35, 95% CI:
      1.05-1.74). However, the odds reduced for infants from Eastern Indonesia
      (OR=0.64, 95% CI: 0.49-0.85). Poor breastfeeding practices are associated with
      environmental, socio-economic, pregnancy-birthing characteristics and maternal
      health services factors. Efforts to promote breastfeeding practices should be
      conducted comprehensively to target population at risk for poor breastfeeding
      practices. 

PMID- 24561978
TI  - The impact on child wasting of a capacity building project implemented by
      community and district health staff in rural Lao PDR.
AB  - Laos is a low-income food-deficit country with pockets of high levels of wasting
      in the highland areas. We implemented a 3-year health/nutrition project in 12
      villages in the highlands of Savannakhet province to reduce acute malnutrition in
      children. Volunteer nutrition teams in each village monitored child growth and
      promoted healthy feeding practices; a multisectoral district committee conducted
      monthly outreach to assess child growth, manage acute malnutrition and deliver
      primary health care services. We conducted a cross-sectional assessment before
      project activities began and at the end of the project. The baseline survey
      randomly sampled 60% of all households; the endline assessment aimed to survey
      all eligible registered participants. Anthropometric measures were taken from
      children aged 6-59 months; mothers with children aged <12 months were asked about
      infant feeding practices, antenatal and post-partum care; and child immunizations
      were recorded for children aged between 0-23 months. At baseline, 721 households
      were sampled, while the endline assessment surveyed between 82% and 100% of
      eligible participants in each age group. Acute malnutrition reduced from 12.4%
      (95% CI: 10.4- 14.3) to 6.1% (4.9-7.3). Unhealthy feeding practices declined: in
      2008, 40.0% (34.7-45.3) of mothers breastfed their newborn within 2 hours of
      birth and 30.8% (25.7-35.8) threw the colostrum away; in 2011, these figures were
      72% and 8% respectively. Maternal care and child immunisation coverage also
      improved. Improving the health environment and child feeding practices appears to
      have markedly reduced the level of wasting. Unsafe feeding practices were common
      but readily changed by the community-based nutrition teams. 

PMID- 24561979
TI  - Disturbed eating tendency and related factors in grade four to six elementary
      school students in Taiwan.
AB  - OBJECTIVE: This study investigated Taiwanese elementary school students' status
      in terms of body size, body satisfaction and disturbed eating tendencies.
      METHODS: In a cross-sectional survey, 1,261 elementary school children from
      grades four to six participated in this study. We used an anonymous selfreported
      questionnaire, which included: demographics and body satisfaction; Children's
      Eating Attitude Test -26 (ChEAT-26); Nowicki-Strickland Locus of Control Scale;
      and Influence of Significant Others Scale and Media Impact Scale. RESULTS: We
      found that 58.4% of the children were of normal weight, and 32.7% of the boys and
      22.2% of the girls were over-weight or obese. Moreover, 39% of the children
      wanted to be thinner. The mean ChEAT-26 score was 8.71+/-8.35, and 10.5% of the
      children were at high risk for disturbed eating tendencies (ChEAT-26>=20),
      including 8.4% of the boys and 12.6% of the girls. Scores on the ChEAT-26,
      Nowicki-Strickland Locus of Control Scale, Influence of Significant Others Scale
      and Media Impact Scale were positively correlated. The level of external control
      and the influence of significant others and the media were significantly higher
      in children with disturbed eating attitudes than in those without them.
      Multivariable logistic regressions showed that disturbed eating attitudes were
      associated with body satisfaction, locus of control, and the level of influence
      of significant others and the media. CONCLUSIONS: Disturbed eating behaviors
      exist among elementary school students in Taiwan. This survey highlights the need
      for education in acquiring healthy mental attitudes and eating behaviors by
      elementary school students.

PMID- 24561980
TI  - Influence of obesogenic behaviors on health-related quality of life in
      adolescents.
AB  - We aimed to prospectively examine the association between the combined effects of
      obesogenic behaviors on quality of life (QOL) in adolescents. Of 2353 Sydney
      schoolchildren surveyed (median age 12.7 years), 1,213 were re-examined 5 years
      later at age 17-18. Children completed activity and food-frequency
      questionnaires. An unhealthy behavior score was calculated, allocating 1 point
      for the following: <60 minutes of total physical activity/ day; >=2 hours of
      screen time/ day; consumed salty snack foods and/or confectionery >=5 times per
      week; >=1 serves of soft drinks and/or cordial/ day; and not consuming both >=2
      serves of fruit and >=3 serves of vegetables/ day. Health-related QOL was
      assessed by the Pediatric Quality of Life Inventory (PedsQL). The prevalence of
      0, 1, 2, 3, 4, and 5 lifestyle risk factors was 4.2%, 17.1%, 30.7%, 30.5%, 13.9%
      and 3.6%, respectively. After multivariable- adjustment, children engaging in 5
      versus 0 unhealthy behaviors had 9.2-units lower PedsQL physical summary score
      (ptrend=0.001), five years later. Boys reporting 4 or 5 lifestyle risk factors
      compared to their peers reporting none or one at baseline, had lower total and
      physical summary scores at follow-up, ptrend=0.02 and 0.01, respectively. Girls
      engaging in 4 or 5 versus 0 or 1 unhealthy behaviors, had 4.6-units lower
      physical summary score (ptrend=0.04), five years later. The number of obesogenic
      lifestyle risk factors was independently associated with subsequent poorer QOL,
      particularly physical health, during adolescence. These findings underscore the
      importance of targeting lifestyle behaviors to promote general well-being and
      physical functioning in adolescents. 

PMID- 24561981
TI  - Breakfast eating patterns and the metabolic syndrome: the Korea National Health
      and Nutrition Examination Survey (KNHANES) 2007-2009.
AB  - OBJECTIVE: The purpose of this study is to find out the association between
      eating breakfast, breakfast patterns, and the metabolic syndrome. METHODS: We
      used the fourth Korean National Health and Nutrition Examination Survey from 2007
      to 2009. A total of 16,734 subjects were included. Breakfast dietary patterns
      were extracted by factor analysis. Multiple logistic regression was used to
      assess the relationship between breakfast consumption, breakfast dietary
      patterns, and the metabolic syndrome. RESULTS: We found that breakfast
      consumption itself reduced the risk of the metabolic syndrome (odds ratio=0.82,
      95% confidence interval=0.69-0.98). We identified two breakfast dietary patterns:
      the traditional Korean pattern and the dairy-cereal pattern. The dairy-cereal
      pattern was associated with a reduction in the risk of the metabolic syndrome
      among breakfast consumers. Compared to no breakfast consumption, the strongest
      traditional Korean pattern and the highest quartiles for the dairy-cereal pattern
      were associated with a reduced risk of the metabolic syndrome. CONCLUSIONS:
      Breakfast consumption is associated with the metabolic syndrome. Not all
      breakfast consumption patterns are associated with a reduced risk of having the
      metabolic syndrome. In particular, eating either a dairy-cereal breakfast or high
      energy and fiber breakfast are associated with a reduced risk of the metabolic
      syndrome.

PMID- 24561982
TI  - Food insecurity and the metabolic syndrome among women from low income
      communities in Malaysia.
AB  - This cross-sectional study examined the relationship between household food
      insecurity and the metabolic syndrome (MetS) among reproductive-aged women
      (n=625) in low income communities. The Radimer/Cornell Hunger and Food Insecurity
      instrument was utilized to assess food insecurity. Anthropometry, diet diversity,
      blood pressure and fasting venous blood for lipid and glucose profile were also
      obtained. MetS was defined as having at least 3 risk factors and is in accordance
      with the Harmonized criteria. The prevalence of food insecurity and MetS was
      78.4% (household food insecure, 26.7%; individual food insecure, 25.3%; child
      hunger, 26.4%) and 25.6%, respectively. While more food secure than food insecure
      women had elevated glucose (food secure, 54.8% vs food insecure, 37.3-46.1%),
      total cholesterol (food secure, 54.1% vs food insecure, 32.1-40.7%) and LDL
      cholesterol (food secure, 63.7% vs food insecure, 40.6-48.7%), the percentage of
      women with overweight/ obesity, abdominal obesity, hypertension, high
      triglyceride, low HDL-cholesterol and MetS did not vary significantly by food
      insecurity status. However, after controlling for demographic and socioeconomic
      covariates, women in food insecure households were less likely to have MetS
      (individual food insecure and child hunger) (p<0.05), abdominal obesity
      (individual food insecure and child hunger) (p<0.01), elevated glucose (household
      food insecure), total cholesterol (child hunger) (p<0.05) and LDL-cholesterol
      (household food insecure and child hunger) (p<0.05) compared to food secure
      women. Efforts to improve food insecurity of low income households undergoing
      nutrition transition should address availability and accessibility to healthy
      food choices and nutrition education that could reduce the risk of diet-related
      chronic diseases. 

PMID- 24561984
TI  - What factors were important for dietary improvement in emergency shelters after
      the Great East Japan Earthquake?
AB  - The Great East Japan Earthquake of 2011 left many evacuees with insufficient food
      and emergency shelter. However, there is no evidence concerning the factors
      affecting dietary circumstances in emergency shelters after disasters. To clarify
      the factors that influenced the provision of meals, we reanalyzed a data set from
      a dietary survey conducted in emergency shelters one month after the Great East
      Japan Earthquake (2011). Among the 69 shelters in "city A," 53 (79.1%) had food
      shortages. The possibility of cooking in the emergency shelter improved the
      provision of meals to evacuees. When comparing emergency shelters with and
      without cooking equipment, the shelters with cooking equipment provided more
      meals, as well as more dishes containing grains and vegetables. When there was a
      gas supply, the twice per day provision of "balanced" meals (containing grains,
      vegetables, and meat/fish) was more frequent than when there was no gas supply.
      Interestingly, neither the water supply nor the electricity supply affected the
      provision of balanced meals. Further, emergency shelters with larger numbers of
      evacuees had a lower possibility of cooking and lower availability of gas supply.
      Our results demonstrate that early improvements to post-disaster meal provision
      may maintain the health of evacuees. Such improvements could be achieved by 1)
      the speedy restoration of the gas supply to enable cooking, and 2) limiting the
      number of evacuees per emergency shelter. 

PMID- 24561983
TI  - Clustering and determinants of cardiometabolic risk factors among Filipino young
      adults.
AB  - BACKGROUND: With modernization, cardiometabolic disease risk has increased in low
      and middle-income countries. To better understand cardiometabolic disease
      etiology, we evaluated the patterning risk factors in a susceptible young adult
      population. METHODS AND RESULTS: Participants included 1,621 individuals from the
      2005 Cebu Longitudinal Health and Nutrition Survey. Using cluster analysis, we
      grouped individuals by the following biomarkers: triglycerides, HDL and LDL
      cholesterol, C-reactive protein, blood pressure, homeostasis model assessment of
      insulin resistance, and fasting glucose. Using multinomial logistic regression
      models we assessed how diet, adiposity, and environment predicted cardiometabolic
      clusters. We identified 5 distinct sexspecific clusters: 1) Healthy/High HDL
      cholesterol (with the addition of high LDL cholesterol in women); 2) Healthy/Low
      blood pressure; 3) High blood pressure; 4) Insulin resistant/High triglycerides;
      and 5) High Creactive protein. Low HDL cholesterol was the most prevalent risk
      factor (63%). In men and women, a higher intake of saturated fat increased the
      likelihood of being in the healthy clusters. In men, poorer environmental hygiene
      increased the likelihood of being in the High C-reactive protein cluster,
      compared to the healthy clusters (OR 0.74 [95% CI 0.60-0.90] and 0.83 [0.70
      0.99]). Adiposity most strongly associated with membership to the Insulin
      resistant/high triglyceride cluster. CONCLUSIONS: Despite the population's youth
      and leanness, cluster analysis found patterns of cardiometabolic risk. While
      adiposity measures predicted clustering, diet and environment also independently
      predicted clustering, emphasizing the importance of screening lean and overweight
      individuals for cardiometabolic risk. Finding predictors of risk in early
      adulthood could help inform prevention efforts for future disease.

PMID- 24561985
TI  - Association of adiponectin gene -11377C>G polymorphism with adiponectin levels
      and the metabolic syndrome in Thais.
AB  - The metabolic syndrome is related to increased risk of developing cardiovascular
      disease and type 2 diabetes. Adiponectin is an adipocyte-secreted protein with
      insulin-sensitizing and anti-atherogenic properties. The aims of this study were
      to evaluate adiponectin levels and biochemical parameters in metabolic-syndrome
      subjects and healthy controls. The study also sought to identify links between
      two polymorphisms, -11377C>G (rs266729) and +45T>G (rs2241766) of the adiponectin
      gene, in relation to adiponectin levels and the metabolic syndrome. Three hundres
      and thirty-two Thai volunteers: 164 metabolic-syndrome subjects and 168 healthy
      control subjects were investigated. The adiponectin and HDL-C levels of the
      metabolic-syndrome group were significantly lower than the control group
      (p<0.001). Decreased concentration of adiponectin was associated with -11377C>G
      polymorphism (p<0.001); this polymorphism was significantly more frequent in the
      metabolic syndrome group than in the control group (p<0.001). However, +45T>G
      polymorphism of the adiponectin gene was found not to be related to adiponectin
      level or metabolic syndrome. Therefore, -11377C>G polymorphism was related to the
      metabolic syndrome susceptibility, and this polymorphism impacted on circulating
      adiponectin concentrations among Thais. 

PMID- 24561986
TI  - The effect of HIF-1alpha on glucose metabolism, growth and apoptosis of
      pancreatic cancerous cells.
AB  - OBJECTIVES: The aim of this study is to explore the possible role of HIF-1alpha
      in glucose metabolism, proliferation and apoptosis of pancreatic cancerous cells.
      METHOD: The pancreatic cancerous BxPC-3 cells were cultured in normoxia or
      hypoxia (3% O2), respectively. Cell proliferation was determined by MTT assay,
      apoptosis was determined by Annexin V/PI staining. Expression of Pyruvate
      dehydrogenase kinase (PDK1), Lactate dehydrogenase (LDHA), pyruvate kinase M2
      (PKM2) and citrate synthase (CS) was determined by Western-blot and Realtime PCR.
      RESULTS: Under hypoxia, the expression of HIF-1alpha and the lactate production
      were increased. The expression of glucose metabolic enzymes PDK1, LDHA, PKM2 was
      also increased compared with that under aerobic condition. Hypoxia treatment had
      little effect on expression of CS. Under hypoxia, knockdown of HIF-1alpha
      inhibited the production of lactate and the expression of PDK1, LDHA and PKM2.
      Knockdown of HIF-1alpha repressed the growth of pancreatic cancer BxPC-3 cells
      and induced apoptosis of the cells under hypoxia. CONCLUSION: Under hypoxia, the
      expression of HIF-1alpha is induced, leading to the increase of glycolysis in
      BxPC-3 cells possibly through upregulation of the enzymes related to glycolysis.
      HIF-1alpha knockdown can inhibit the prolife ratio and promote apoptosis of
      pancreatic cancerous BxPC-3 cells in vitro.

PMID- 24561988
TI  - Communicable disease control programmes and health systems: an analytical
      approach to sustainability.
AB  - There is renewed concern over the sustainability of disease control programmes,
      and re-emergence of policy recommendations to integrate programmes with general
      health systems. However, the conceptualization of this issue has remarkably
      received little critical attention. Additionally, the study of programmatic
      sustainability presents methodological challenges. In this article, we propose a
      conceptual framework to support analyses of sustainability of communicable
      disease programmes. Through this work, we also aim to clarify a link between
      notions of integration and sustainability. As a part of development of the
      conceptual framework, we conducted a systematic literature review of peer
      reviewed literature on concepts, definitions, analytical approaches and empirical
      studies on sustainability in health systems. Identified conceptual proposals for
      analysis of sustainability in health systems lack an explicit conceptualization
      of what a health system is. Drawing upon theoretical concepts originating in
      sustainability sciences and our review here, we conceptualize a communicable
      disease programme as a component of a health system which is viewed as a complex
      adaptive system. We propose five programmatic characteristics that may explain a
      potential for sustainability: leadership, capacity, interactions (notions of
      integration), flexibility/adaptability and performance. Though integration of
      elements of a programme with other system components is important, its role in
      sustainability is context specific and difficult to predict. The proposed
      framework might serve as a basis for further empirical evaluations in
      understanding complex interplay between programmes and broader health systems in
      the development of sustainable responses to communicable diseases. 

PMID- 24561989
TI  - Whole myocardium tracking in 2D-echocardiography in multiple orientations using a
      motion constrained level-set.
AB  - The segmentation and tracking of the myocardium in echocardiographic sequences is
      an important task for the diagnosis of heart disease. This task is difficult due
      to the inherent problems of echographic images (i.e. low contrast, speckle noise,
      signal dropout, presence of shadows). In this article, we extend a level-set
      method recently proposed in Dietenbeck et al. (2012) in order to track the whole
      myocardium in echocardiographic sequences. To this end, we enforce temporal
      coherence by adding a new motion prior energy to the existing framework. This
      motion prior term is expressed as new constraint that enforces the conservation
      of the levels of the implicit function along the image sequence. Moreover, the
      robustness of the proposed method is improved by adjusting the associated
      hyperparameters in a spatially adaptive way, using the available strong a priori
      about the echocardiographic regions to be segmented. The accuracy and robustness
      of the proposed method is evaluated by comparing the obtained segmentation with
      experts references and to another state-of-the-art method on a dataset of 15
      sequences (? 900 images) acquired in three echocardiographic views. We show that
      the algorithm provides results that are consistent with the inter-observer
      variability and outperforms the state-of-the-art method. We also carry out a
      complete study on the influence of the parameters settings. The obtained results
      demonstrate the stability of our method according to those values. 

PMID- 24561990
TI  - Comparison of Fibrotest and PGAA for the diagnosis of fibrosis stage in patients
      with alcoholic liver disease.
AB  - BACKGROUND AND AIMS: The PGAA index was one of the first composite liver fibrosis
      markers. This study aims, prospectively, to confirm the diagnostic value of PGAA
      and Fibrotest in patients with alcoholic liver disease and to compare their
      diagnostic performances. PATIENTS AND METHODS: We prospectively included 200
      consecutive patients (159 men and 41 women; mean age: 51+/-0.7 years).The PGAA
      index was calculated by combining the results of four laboratory tests
      (prothrombin time, gamma-glutamyl transpeptidase, apolipoprotein A1, and alpha-2
      macroglobulin) scored on a 0-4 scale. The Fibrotest score was computed using the
      Biopredictive website. The overall diagnostic performances of scores were
      evaluated in terms of the area under the receiver operating characteristic
      (AUROC) curve. The Obuchowski measure was assessed taking into account the
      distribution of fibrosis stages observed in the cohort. RESULTS: For predicting
      F>=2 fibrosis stage, the AUROC curves of PGAA and Fibrotest were 0.83+/-0.03 and
      0.80+/-0.03, respectively. For predicting F4 fibrosis stage, the AUROC curves of
      PGAA and Fibrotest were 0.87+/-0.03 and 0.86+/-0.03. There was no difference
      between the AUROC curves of PGAA and Fibrotest. The Obuchowski measure was 0.92+/
      0.01 for PGAA and Fibrotest. For a value of 10, PGAA had 98% specificity and 97%
      positive predictive value for the detection of F>=2 fibrosis stage and 80%
      sensitivity and 92% negative predictive value for F4 stage fibrosis. CONCLUSION:
      We confirm the comparable diagnostic values of Fibrotest and PGAA. When Fibrotest
      use is constrained by an increase in unconjugated bilirubin or is not financially
      viable, PGAA may be an alternative.

PMID- 24561993
TI  - ERP correlates of word onset priming in infants and young children.
AB  - Using word onset priming with early learned words, we tracked access to
      phonological representations and predictive phonological processing at 6, 12, 18,
      and 24 months after birth. Event-Related Potentials (ERPs) were recorded while
      participants heard German word onsets (primes) followed by disyllabic spoken
      words (targets). Primes and target onsets were either congruent or incongruent
      (ma - Mama vs. so - Mama [Engl. 'mommy']). For an adult control group, ERP
      differences were found for the N100 complex, which has been related to abstract
      auditory analysis; and for the P350 deflection, which has been related to lexical
      access. A combined analysis of all infants and young children revealed an
      immature instance of an N100 effect, suggesting adult-like abstract speech sound
      processing. A central negativity effect, which had formerly been obtained when
      adults or older children were engaged in a lexical decision task, suggests that
      adult-like predictive phonological processing is available early in infancy.
      However, the absence of a P350-like effect in the infant data suggests that adult
      like access to phonological forms is not established in the first two years of
      life. Taken together, ERPs recorded in word onset priming proved useful in
      investigating early phonological processing without an explicit behavioral
      measure. 

PMID- 24561991
TI  - Neonatal genome-wide methylation patterns in relation to birth weight in the
      Norwegian Mother and Child Cohort.
AB  - Although epigenetic regulation plays a critical role in embryonic development,
      few studies have examined the relationship of epigenome-wide methylation with
      fetal growth. Using the Infinium HumanMethylation450 BeadChip (Illumina, Inc.,
      San Diego, California) in a substudy of 1,046 infants from the Norwegian Mother
      and Child Cohort Study (MoBa) enrolled between 1999 and 2008, we examined
      epigenome-wide cord blood DNA methylation in relation to birth weight. In
      multivariable-adjusted robust linear regression models, we identified
      differential methylation at 19 cytosine-guanine dinucleotides (CpGs) associated
      with either decreased (AT-rich interactive domain 5B (MRF1-like) (ARID5B), 2
      CpGs) or increased (x-ray repair complementing defective repair in Chinese
      hamster cells 3 (XRCC3), 4 CpGs) birth weight. ARID5B knockout mice have less
      adipose tissue and significantly lower weight in the postnatal period. XRCC3
      plays a key role in the maintenance of chromosome stability and the repair of DNA
      damage. Although there are fewer data on the other implicated genes, many of
      these genes have been shown to have roles in developmental processes. This
      constitutes the largest and most robust study of birth weight using an epigenome
      wide methylation platform and offers potential insights into epigenetic
      mechanisms of fetal growth. 

PMID- 24561992
TI  - Chronic physical health consequences of being injured during the terrorist
      attacks on World Trade Center on September 11, 2001.
AB  - Few studies have focused on injuries from the World Trade Center disaster on
      September 11, 2001. Severe injury has health consequences, including an increased
      mortality risk 10 years after injury and the risk of mental health problems, such
      as posttraumatic stress disorder (PTSD). The World Trade Center Health Registry
      identified 14,087 persons with none of a selected group of preexisting chronic
      conditions before 2002 who were present during and soon after the World Trade
      Center attacks, 1,980 of whom reported sustaining 1 or more types of injury
      (e.g., a broken bone or burn). Survey data obtained during 2003-2004 and 2006
      2007 were used to assess the odds of reporting a diagnosis of chronic conditions
      (heart disease, respiratory disease, diabetes, cancer) up to 5-6 years after the
      attacks. Number of injury types and probable PTSD were significantly associated
      with having any chronic conditions diagnosed in 2002-2007. Persons with multiple
      injuries and PTSD had a 3-fold higher risk of heart disease than did those with
      no injury and no PTSD, and persons with multiple injuries and with no PTSD had a
      2-fold higher risk of respiratory diseases. The present study shows that injured
      persons with or without comorbid PTSD have a higher risk of developing chronic
      diseases. Clinicians should be aware of the heightened risk of chronic heart and
      respiratory conditions among injured persons. 

PMID- 24561994
TI  - Ethanol production via simultaneous saccharification and fermentation of sodium
      hydroxide treated corn stover using Phanerochaete chrysosporium and Gloeophyllum
      trabeum.
AB  - Ethanol was produced via the simultaneous saccharification and fermentation (SSF)
      of dilute sodium hydroxide treated corn stover. Saccharification was achieved by
      cultivating either Phanerochaete chrysosporium or Gloeophyllum trabeum on the
      treated stover, and fermentation was then performed by using either Saccharomyces
      cerevisiae or Escherichia coli K011. Ethanol production was highest on day 3 for
      the combination of G. trabeum and E. coli K011 at 6.68 g/100g stover, followed by
      the combination of P. chrysosporium and E. coli K011 at 5.00 g/100g stover. SSF
      with S. cerevisiae had lower ethanol yields, ranging between 2.88 g/100g stover
      at day 3 (P. chrysosporium treated stover) and 3.09 g/100g stover at day 4 (G.
      trabeum treated stover). The results indicated that mild alkaline pretreatment
      coupled with fungal saccharification offers a promising bioprocess for ethanol
      production from corn stover without the addition of commercial enzymes.

PMID- 24561995
TI  - Making Drosophila lineage-restricted drivers via patterned recombination in
      neuroblasts.
AB  - The Drosophila cerebrum originates from about 100 neuroblasts per hemisphere,
      with each neuroblast producing a characteristic set of neurons. Neurons from a
      neuroblast are often so diverse that many neuron types remain unexplored. We
      developed new genetic tools that target neuroblasts and their diverse
      descendants, increasing our ability to study fly brain structure and development.
      Common enhancer-based drivers label neurons on the basis of terminal identities
      rather than origins, which provides limited labeling in the heterogeneous
      neuronal lineages. We successfully converted conventional drivers that are
      temporarily expressed in neuroblasts, into drivers expressed in all subsequent
      neuroblast progeny. One technique involves immortalizing GAL4 expression in
      neuroblasts and their descendants. Another depends on loss of the GAL4 repressor,
      GAL80, from neuroblasts during early neurogenesis. Furthermore, we expanded the
      diversity of MARCM-based reagents and established another site-specific mitotic
      recombination system. Our transgenic tools can be combined to map individual
      neurons in specific lineages of various genotypes. 

PMID- 24561996
TI  - Opioids induce dissociable forms of long-term depression of excitatory inputs to
      the dorsal striatum.
AB  - As prescription opioid analgesic abuse rates rise, so does the need to understand
      the long-term effects of opioid exposure on brain function. The dorsal striatum
      is an important site for drug-induced neuronal plasticity. We found that
      exogenously applied and endogenously released opioids induced long-term
      depression (OP-LTD) of excitatory inputs to the dorsal striatum in mice and rats.
      Mu and delta OP-LTD, although both being presynaptically expressed, were
      dissociable in that they summated, differentially occluded endocannabinoid-LTD
      and inhibited different striatal inputs. Kappa OP-LTD showed a unique subregional
      expression in striatum. A single in vivo exposure to the opioid analgesic
      oxycodone disrupted mu OP-LTD and endocannabinoid-LTD, but not delta or kappa OP
      LTD. These data reveal previously unknown opioid-mediated forms of long-term
      striatal plasticity that are differentially affected by opioid analgesic exposure
      and are likely important mediators of striatum-dependent learning and behavior. 

PMID- 24561997
TI  - Two types of asynchronous activity in networks of excitatory and inhibitory
      spiking neurons.
AB  - Asynchronous activity in balanced networks of excitatory and inhibitory neurons
      is believed to constitute the primary medium for the propagation and
      transformation of information in the neocortex. Here we show that an
      unstructured, sparsely connected network of model spiking neurons can display two
      fundamentally different types of asynchronous activity that imply vastly
      different computational properties. For weak synaptic couplings, the network at
      rest is in the well-studied asynchronous state, in which individual neurons fire
      irregularly at constant rates. In this state, an external input leads to a highly
      redundant response of different neurons that favors information transmission but
      hinders more complex computations. For strong couplings, we find that the network
      at rest displays rich internal dynamics, in which the firing rates of individual
      neurons fluctuate strongly in time and across neurons. In this regime, the
      internal dynamics interact with incoming stimuli to provide a substrate for
      complex information processing and learning. 

PMID- 24561998
TI  - Sparse, decorrelated odor coding in the mushroom body enhances learned odor
      discrimination.
AB  - Sparse coding may be a general strategy of neural systems for augmenting memory
      capacity. In Drosophila melanogaster, sparse odor coding by the Kenyon cells of
      the mushroom body is thought to generate a large number of precisely addressable
      locations for the storage of odor-specific memories. However, it remains untested
      how sparse coding relates to behavioral performance. Here we demonstrate that
      sparseness is controlled by a negative feedback circuit between Kenyon cells and
      the GABAergic anterior paired lateral (APL) neuron. Systematic activation and
      blockade of each leg of this feedback circuit showed that Kenyon cells activated
      APL and APL inhibited Kenyon cells. Disrupting the Kenyon cell-APL feedback loop
      decreased the sparseness of Kenyon cell odor responses, increased inter-odor
      correlations and prevented flies from learning to discriminate similar, but not
      dissimilar, odors. These results suggest that feedback inhibition suppresses
      Kenyon cell activity to maintain sparse, decorrelated odor coding and thus the
      odor specificity of memories. 

PMID- 24561999
TI  - Object-based attention involves the sequential activation of feature-specific
      cortical modules.
AB  - Object-based theories of attention propose that the selection of an object's
      feature leads to the rapid selection of all other constituent features, even
      those that are task irrelevant. We used magnetoencephalographic recordings to
      examine the timing and sequencing of neural activity patterns in feature-specific
      cortical areas as human subjects performed an object-based attention task.
      Subjects attended to one of two superimposed moving dot arrays that were
      perceived as transparent surfaces on the basis either of color or speed of
      motion. When surface motion was attended, the magnetoencephalographic waveforms
      showed enhanced activity in the motion-specific cortical area starting at ~ 150
      ms after motion onset, followed after ~ 60 ms by enhanced activity in the color
      specific area. When surface color was attended, this temporal sequence was
      reversed. This rapid sequential activation of the relevant and irrelevant feature
      modules provides a neural basis for the binding of an object's features into a
      unitary perceptual experience.

PMID- 24562001
TI  - Evaluation of nutrition deficits in adult and elderly trauma patients.
AB  - BACKGROUND: As metabolism is often escalated following injury, severely injured
      trauma patients are at risk for underfeeding and adverse outcomes. METHODS: From
      an international database of 12,573 critically ill, adult mechanically ventilated
      patients, who received a minimum of 3 days of nutrition therapy, trauma patients
      were identified and nutrition practices and outcomes compared with nontrauma
      patients. Within the trauma population, we compared nutrition practices and
      outcomes of younger vs older patients. RESULTS: There were 1279 (10.2%) trauma
      patients. They were younger, were predominantly male, had lower Acute Physiology
      and Chronic Health Evaluation II (APACHE II) scores, and had an overall lower
      body mass index compared with nontrauma patients. Eighty percent of trauma
      patients received enteral feeding compared with 78% of nontrauma patients. Trauma
      patients were prescribed more calories and protein yet received similar amounts
      as nontrauma patients. Nutrition adequacy was reduced in both trauma and
      nontrauma patients. Survival was higher in trauma patients (86.6%) compared with
      nontrauma patients (71.8%). When patients who died were included as never
      discharged, trauma patients were more rapidly discharged from the intensive care
      unit (ICU) and hospital. Within the trauma population, 17.5% were elderly (>=65
      years). The elderly had increased days of ventilation, ICU stay, and mortality
      compared with younger trauma patients. In a multivariable model, age and APACHE
      II score, but not nutrition adequacy, were associated with time to discharge
      alive from the hospital. CONCLUSION: Significant nutrition deficits were noted in
      all patients. Elderly trauma patients have worse outcomes compared with younger
      patients. Further studies are necessary to evaluate whether increased nutrition
      intake can improve the outcomes of trauma patients, especially geriatric trauma
      patients.

PMID- 24562002
TI  - Examination of accuracy in the assessment of gastric residual volume: a
      simulated, controlled study.
AB  - BACKGROUND: Increased gastric content from enteral nutrition intolerance is
      thought to place patients at risk for pulmonary aspiration. Although considered a
      questionable practice, blind gastric tube aspiration is the most common approach
      to measure gastric content. This simulated study evaluated the accuracy of
      residual volume (RV) assessment via tube aspirations made from known volumes by
      controlling the syringe pull technique, feeding tube properties, fluid viscosity,
      and placement of tubes in the fluid. MATERIALS AND METHODS: This study was
      conducted in a metrology laboratory. Aspirates were obtained using a force
      measurement test system to control force of the syringe pull technique using 3
      different procedures (slow 10 inches per minute [ipm], intermittent 10 ipm, and
      fast 40 ipm). Four different feeding tubes, 10 Fr and 18 Fr, each made of
      polyurethane and polyvinyl chloride, were placed in varying depths of 100 mL of
      either water or formula. The effect of fluid viscosity was also examined.
      RESULTS: Overall, 108 RVs were analyzed using a force measurement test system.
      Actual content of RV was underestimated 19% on average and varied across tube
      size and viscosity. Intermittent and slow syringe pull techniques yielded greater
      aspirate quantities, although neither technique aspirated the full amount of
      volume available. The 10 Fr feeding tubes yielded larger RVs in more viscous
      fluid, yet the 18 Fr tubes performed better with fluids of lower viscosity.
      CONCLUSIONS: Based on this simulation, RV assessment does not accurately reflect
      the total volume of the contents available and, therefore, the clinical utility
      of this assessment should be further investigated.

PMID- 24562000
TI  - Palmitoylation of delta-catenin by DHHC5 mediates activity-induced synapse
      plasticity.
AB  - Synaptic cadherin adhesion complexes are known to be key regulators of synapse
      plasticity. However, the molecular mechanisms that coordinate activity-induced
      modifications in cadherin localization and adhesion and the subsequent changes in
      synapse morphology and efficacy remain unknown. We demonstrate that the
      intracellular cadherin binding protein delta-catenin is transiently palmitoylated
      by DHHC5 after enhanced synaptic activity and that palmitoylation increases delta
      catenin-cadherin interactions at synapses. Both the palmitoylation of delta
      catenin and its binding to cadherin are required for activity-induced
      stabilization of N-cadherin at synapses and the enlargement of postsynaptic
      spines, as well as the insertion of GluA1 and GluA2 subunits into the synaptic
      membrane and the concomitant increase in miniature excitatory postsynaptic
      current amplitude. Notably, context-dependent fear conditioning in mice resulted
      in increased delta-catenin palmitoylation, as well as increased delta-catenin
      cadherin associations at hippocampal synapses. Together these findings suggest a
      role for palmitoylated delta-catenin in coordinating activity-dependent changes
      in synaptic adhesion molecules, synapse structure and receptor localization that
      are involved in memory formation. 

PMID- 24562008
TI  - Feasibility of segmental resection in non-small-cell lung cancer with ground
      glass opacity.
AB  - OBJECTIVES: Recently, lung segmental resection has been increasingly performed in
      patients with lung cancer. In this study, the results of radical segmentectomy
      (RS) and palliative segmentectomy (PS) were compared retrospectively. METHODS:
      Segmentectomy was performed to remove a primary lung cancer in 87 cases. RS was
      performed for pure ground-glass opacity (GGO), >50% GGO and diameter less than 2
      cm and less than 10 mm solid tumours. PS was performed in patients with poor lung
      function or relapse, or at high risk for surgery. A total of 84 cases, excluding
      3 cases of relapse, were investigated. RESULTS: The pathological stage of RS was
      IA in 32 (94.1%) and IB in 2 (5.9%). The pathological stage of PS was IA in 23
      (46.0%), IB in 15 (30.0%), IIA in 5 (10.0%), IIB in 1 (2.0%), IIIA in 4 (8.0%)
      and IV in 2 (4.0%). The preoperative characteristics of RS were compared with
      those of PS for pathological stage I. The mean age was significantly lower for RS
      cases (67.4 +/- 9.9 years) than for PS cases (73.0 +/- 9.0 years; P = 0.013).
      Tumour size was significantly smaller in RS cases (14.7 +/- 4.6 mm) than in PS
      cases (22.0 +/- 8.9 mm; P < 0.001). The tumour standardized uptake value of 18F
      fluorodeoxyglucose positron emission tomography was significantly lower in RS
      cases (1.2 +/- 1.6) than in PS cases (6.0 +/- 6.1; P < 0.001). Serum
      carcinoembryonic antigen level was lower in RS cases (2.8 +/- 1.8 ng/ml) than in
      PS cases (4.9 +/- 5.0; P = 0.019). The mean duration of drainage was shorter in
      RS (2.5 +/- 0.7 days) than in PS (3.9 +/- 2.6 days; P = 0.004). Postoperative
      complications occurred in 6 RS cases (17.6%) and 12 PS cases (29.3%). Overall 5
      year survival was higher in RS (100%) than in PS (66.2%; P = 0.003). Five-year
      disease-free survival was higher in RS (100%) than in PS (66.2%; P = 0.002).
      Recurrence was detected in 6 PS patients; 10 PS cases showed tumour with GGO and
      survived without recurrence. CONCLUSIONS: Our RS is feasible for stage I lung
      cancer with specific computed tomography features, such as small size, GGO or
      peripheral location.

PMID- 24562007
TI  - European guidelines on structure and qualification of general thoracic surgery.
AB  - OBJECTIVE: To update the recommendations for the structural characteristics of
      general thoracic surgery (GTS) in Europe in order to provide a document that can
      be used as a guide for harmonizing the general thoracic surgical practice in
      Europe. METHODS: A task force was created to set the structural, procedural and
      qualification characteristics of a European GTS unit. These criteria were
      endorsed by the Executive Committee of the European Society of Thoracic Surgeons
      and by the Thoracic Domain of the European Association for Cardio-Thoracic
      Surgery and were validated by the European Board of Thoracic Surgery at European
      Union of Medical Specialists. RESULTS: Criteria regarding definition and scope of
      GTS, structure and qualification of GTS unit, training and education and
      recommendations for subjects of particular interest (lung transplant, oesophageal
      surgery, minimally invasive thoracic surgery, quality surveillance) were
      developed. CONCLUSIONS: This document will hopefully represent the first step of
      a process of revision of the modern thoracic surgeons' curricula, which need to
      be qualitatively rethought in the setting of the qualification process. The
      structural criteria highlighted in the present document are meant to help and
      tackle the challenge of cultural and language barriers as well as of widely
      varying national training programmes.

PMID- 24562009
TI  - Mechanisms of functional mitral regurgitation in cardiomyopathy secondary to
      anterior infarction.
AB  - OBJECTIVES: It remains unclear why some patients with cardiomyopathy secondary to
      anterior infarction do, and others do not develop functional mitral regurgitation
      (MR). METHODS: Thirty-six patients after anterior infarction with ejection
      fraction (EF) below 35%, 18 with no/trivial and 18 with moderate/severe MR,
      underwent cardiac magnetic resonance imaging. Parameters describing the geometry
      of the mitral valve, subvalvular apparatus and left ventricle were measured.
      RESULTS: The septolateral and commissure-to-commissure mitral annular diameters
      were bigger in patients with MR. The odds ratio (OR) of developing regurgitation
      was 25.0 (95% confidence interval [95% CI] 4.3-144.3; P < 0.001) for end-systolic
      septolateral mitral annulus diameter above 20 mm/m(2). MR was less likely in
      patients with straighter posterior papillary muscle (OR 0.040, 95% CI 0.007-0.23;
      P < 0.001-for the angle between muscle axis and mitral annulus plane >81 degrees
      ), and more likely (OR 7.9, 95% CI 1.6-39.4; P = 0.008) with posterior papillary
      muscle tethering >23 mm/m(2). Regurgitation was less likely (OR 0.032, 95% CI
      0.003-0.33; P = 0.001) with anterolateral papillary muscle tip to ipsilateral
      mitral annulus distance in end-diastole longer than 13 mm/m(2). Left ventricular
      EF, volumes and the overall end-systolic and end-diastolic wall thicknesses did
      not differ between the groups. Patients with MR had thinner myocardium proximal
      to the base of the anterior and distal to the base of the posterior papillary
      muscle. CONCLUSIONS: Inferior extension of anterior infarction and more leaning
      posterior papillary muscle are the major components resulting in the development
      of ischaemic MR in patients with cardiomyopathy secondary to anterior infarction.
      Shorter chordae tendineae may constitute the anatomical background that makes the
      development of ischaemic MR more likely.

PMID- 24562010
TI  - Mechanisms of paracrine cardioprotection by cord blood mesenchymal stromal cells.
AB  - OBJECTIVES: Among the mechanisms by which somatic stem cells may improve left
      ventricular function in ischaemic heart disease are pro-survival stimuli mediated
      by secreted factors. This phenomenon is frequently referred to, but remains
      poorly understood. We therefore investigated the non-regenerative
      cardioprotective effects of cord blood mesenchymal stromal cells (CBMSCs) in
      vitro and sought to identify relevant intracellular signalling pathways. METHODS:
      Conditioned medium from CBMSCs and fibroblasts was prepared, and secreted factors
      were analysed by Luminex((r)) immunobead assay. Murine cardiomyocyte-derived HL-1
      cells were subjected to simulated ischaemia by glucose and serum deprivation and
      hypoxia in CBMSC-conditioned or cell-free control medium or in medium conditioned
      by foreskin fibroblasts. The proportions of vital, apoptotic and necrotic cells
      (poly-caspase activity, annexin V and ethidium homodimer-III staining) were
      quantified using a high-content imaging system. Metabolic activity and
      proliferation rate were determined via 3-(4,5-dimethylthiazol-2-yl)-5-(3
      carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium and 5-bromo-2-deoxyuridine
      assays. Phosphorylation of Akt, extracellular-signal-regulated kinase (ERK)1/2,
      signal transducer and activator of transcription 3 (STAT3) and glycogen synthase
      kinase 3beta was determined by western blot, and experiments were repeated in the
      presence of specific small-molecule inhibitors (Wortmannin, UO126 and Stattic).
      RESULTS: CBMSC medium reduced the proportion of dead HL-1 cardiomyocytes from 39
      +/- 3 to 28 +/- 1% (P < 0.05) and the rate of late apoptotic cells to 68 +/- 2%
      of that in control medium (P < 0.001). Metabolic activity was increased by 12 +/-
      1% compared with control (P < 0.05), while in fibroblast medium it was not (5 +/-
      2%, P = 1). This was associated with increased phosphorylation of Akt (2-fold, P
      < 0.05), ERK1/2 (3-fold, P < 0.01) and STAT3 (12-fold, P < 0.001). Combined
      blocking of the phosphatidylinositol-4,5-bisphosphate 3-kinase/Akt and mitogen
      activated protein kinase/ERK signalling abolished the protective CBMSC effect,
      while blocking the pathways individually had no effect. Inhibition of STAT3
      phosphorylation drastically lowered HL-1 cell viability in control medium, but
      not in medium conditioned by CBMSCs. CONCLUSIONS: The factors released by CBMSCs
      protect cardiomyocyte-like HL-1 cells from simulated ischaemia more than those
      released from fibroblasts. While CBMSC-triggered Akt and ERK1/2 activation
      provides protection in a compensatory manner, STAT3 is crucial for cardiomyocyte
      survival in ischaemia, but is not a key mediator of cytoprotective stem cell
      actions.

PMID- 24562012
TI  - A practical guide to phylogenetics for nonexperts.
AB  - Many researchers, across incredibly diverse foci, are applying phylogenetics to
      their research question(s). However, many researchers are new to this topic and
      so it presents inherent problems. Here we compile a practical introduction to
      phylogenetics for nonexperts. We outline in a step-by-step manner, a pipeline for
      generating reliable phylogenies from gene sequence datasets. We begin with a user
      guide for similarity search tools via online interfaces as well as local
      executables. Next, we explore programs for generating multiple sequence
      alignments followed by protocols for using software to determine best-fit models
      of evolution. We then outline protocols for reconstructing phylogenetic
      relationships via maximum likelihood and Bayesian criteria and finally describe
      tools for visualizing phylogenetic trees. While this is not by any means an
      exhaustive description of phylogenetic approaches, it does provide the reader
      with practical starting information on key software applications commonly
      utilized by phylogeneticists. The vision for this article would be that it could
      serve as a practical training tool for researchers embarking on phylogenetic
      studies and also serve as an educational resource that could be incorporated into
      a classroom or teaching-lab.

PMID- 24562019
TI  - Defect detection for corner cracks in steel billets using a wavelet
      reconstruction method.
AB  - Presently, automatic inspection algorithms are widely used to ensure high-quality
      products and achieve high productivity in the steelmaking industry. In this
      paper, we propose a vision-based method for detecting corner cracks on the
      surface of steel billets. Because of the presence of scales composed of oxidized
      substances, the billet surfaces are not uniform and vary considerably with the
      lighting conditions. To minimize the influence of scales and improve the accuracy
      of detection, a detection method based on a visual inspection algorithm is
      proposed. Wavelet reconstruction is used to reduce the effect of scales. Texture
      and morphological features are used to identify the corner cracks among the
      defective candidates. Finally, the experimental results show that the proposed
      algorithm is effective in detecting corner cracks on the surfaces of the steel
      billets. 

PMID- 24562020
TI  - Second-order moments of an electromagnetic Gaussian Schell-model beam in a
      uniaxial crystal.
AB  - We derive the analytical expressions for the second-order moments of an
      electromagnetic Gaussian Schell-model (EGSM) beam propagating in a uniaxial
      crystal. With the help of the derived formulas, we study the evolution properties
      of the propagation factor, the effective radius of curvature and the Rayleigh
      range of an EGSM beam in a uniaxial crystal. It is found that the evolution
      properties of an EGSM beam in a uniaxial crystal are much different from its
      evolution properties in free space and are closely determined by the initial beam
      parameters and the parameters of the uniaxial crystal. The uniaxial crystal
      provides one way for modulating the properties of an EGSM beam. 

PMID- 24562021
TI  - Scalar wave scattering in spherical cavity resonator with conical channels.
AB  - We study the scalar wave scattering off the spherical cavity resonator with two
      finite-length conical channels attached. We use the boundary wall method to
      explore the response of the system to changes in control parameters, such as the
      size of the structure and the angular width of the input and output channels, as
      well as their relative angular position. We found that the system is more
      sensitive to changes in the input channel, and a standing wave phase distribution
      occurs within the cavity for nontransmitting values of the incident wave number.
      We also saw that an optical vortex can travel unaffected through the system with
      aligned channels. 

PMID- 24562018
TI  - Fast and accurate metrology of multi-layered ceramic materials by an automated
      boundary detection algorithm developed for optical coherence tomography data.
AB  - Optical coherence tomography (OCT) is useful for materials defect analysis and
      inspection with the additional possibility of quantitative dimensional metrology.
      Here, we present an automated image-processing algorithm for OCT analysis of roll
      to-roll multilayers in 3D manufacturing of advanced ceramics. It has the
      advantage of avoiding filtering and preset modeling, and will, thus, introduce a
      simplification. The algorithm is validated for its capability of measuring the
      thickness of ceramic layers, extracting the boundaries of embedded features with
      irregular shapes, and detecting the geometric deformations. The accuracy of the
      algorithm is very high, and the reliability is better than 1 MUm when evaluating
      with the OCT images using the same gauge block step height reference. The method
      may be suitable for industrial applications to the rapid inspection of
      manufactured samples with high accuracy and robustness.

PMID- 24562022
TI  - Manipulation of radial-variant polarization for creating tunable bifocusing
      spots.
AB  - We propose and generate a new radial-variant vector field (RV-VF) with a
      distribution of states of polarization described by the square of the radius and
      exploit its focusing property. Theoretically, we present the analytical
      expressions for the three-dimensional electric field of the vector field focused
      by a thin lens under the nonparaxial and paraxial approximations based on the
      vectorial Rayleigh-Sommerfeld formulas. Numerical simulations indicate that this
      focused field exhibits bifocusing spots along the optical axis. The underlying
      mechanism for generating the bifocusing property is analyzed in detail. We give
      the analytical formula for the interval between two foci. Experimentally, we
      generate the RV-VFs with alterable topological charge and demonstrate that the
      interval between two foci is controllable by tuning the radial topological
      charge. This particular focal field has specific applications for biparticle
      trapping, manipulating, alignment, transportation, and accelerating along the
      optical axis. 

PMID- 24562023
TI  - Intensity-interferometric spectral-domain optical coherence tomography with
      dispersion cancellation.
AB  - We describe a technique for cancelling group-velocity dispersion in spectral
      domain (SD) optical coherence tomography (OCT) based on classical intensity
      correlations. As a classical analogue of quantum OCT, a Hong-Ou-Mandel
      interferometer is combined with a conventional SD-OCT setup, and correlations
      between different spectral intensities are calculated. It is shown theoretically
      that a simple computational procedure used in SD-OCT enables scanless cross
      sectional imaging with both dispersion cancellation and a factor-of-?2 resolution
      enhancement. The method involves no ultrafast detectors and works with common
      light sources.

PMID- 24562024
TI  - Resonant angular conversion in a Fabry-Perot resonator holding a dielectric
      cylinder.
AB  - Light transmission through a Fabry-Perot resonator (FPR) holding a dielectric
      cylinder rod is considered. For the cylinder parallel to mirrors of the FPR and
      the mirrors mimicked by the delta functions we present an exact analytical
      theory. It is shown that light transmits only for resonant incident angles,
      alpha(m), similar to the empty FPR. However after transmission the light scatters
      into different resonant angles, alpha(m'), performing resonant angular
      conversion. We compare the theory with experiment in the FPR, exploring
      multilayer films as the mirrors and glass cylinder with diameter coincided with
      the distance between the FPR mirrors. The measured values of angular light
      conversion agree qualitatively with the theoretical results.

PMID- 24562025
TI  - Tapered dual elliptical plasmon waveguides as highly efficient terahertz
      connectors between approximate plate waveguides and two-wire waveguides.
AB  - We present a tapered dual elliptical plasmon waveguide for terahertz waves. This
      element is composed of a pair of tapered elliptical metal structures and is
      especially suitable for the coupling of terahertz waves from an approximate plate
      waveguide to a two-wire waveguide. The long axes of the two ellipses gradually
      reduce to the same sizes as the short axes, and thus the two-ellipse structure is
      now a two-wire waveguide. The slowly tapered structure eliminates the reflection
      and scattering during the coupling process according to WKB approximation. The
      numerical result shows that the coupling efficiency of this connector can reach
      as high as 94%. 

PMID- 24562026
TI  - Hermite-Gaussian modal laser beams with orbital angular momentum.
AB  - A relationship for the complex amplitude of generalized paraxial Hermite-Gaussian
      (HG) beams is deduced. We show that under certain parameters, these beams
      transform into the familiar HG modes and elegant HG beams. The orbital angular
      momentum (OAM) of a linear combination of two generalized HG beams with a phase
      shift of pi/2, with their double indices composed of adjacent integer numbers
      taken in direct and inverse order, is calculated. The modulus of the OAM is shown
      to be an integer number for the combination of two HG modes, always equal to
      unity for the superposition of two elegant HG beams, and a fractional number for
      two hybrid HG beams. Interestingly, a linear combination of two such HG modes
      also presents a mode that is characterized by a nonzero OAM and the lack of
      radial symmetry but does not rotate during propagation. 

PMID- 24562027
TI  - Fast multiscale directional filter bank-based speckle mitigation in gallstone
      ultrasound images.
AB  - Speckle noise is a multiplicative type of noise commonly seen in medical and
      remote sensing images. It gives a granular appearance that degrades the quality
      of the recorded images. These speckle noise components need to be mitigated
      before the image is used for further processing and analysis. This paper presents
      a novel approach for removing granular speckle noise in gray scale images. We
      used an efficient multiscale image representation scheme named fast multiscale
      directional filter bank (FMDFB) along with simple threshold methods such as
      Vishushrink for image processing. It is a perfect reconstruction framework that
      can be used for a wide range of image processing applications because of its
      directionality and reduced computational complexity. The FMDFB-based speckle
      mitigation is appealing over other traditional multiscale approaches such as
      wavelets and Contourlets. Our experimental results show that the despeckling
      performance of the proposed method outperforms the wavelet and Contourlet-based
      despeckling methods. 

PMID- 24562028
TI  - Vertical mode expansion method for transmission of light through a single
      circular hole in a slab.
AB  - An efficient method is developed for rigorously analyzing the scattering of light
      by a layered circular cylindrical object in a layered background, and it is
      applied to the study of the transmission of light through a subwavelength hole in
      a metallic film, where the hole may be filled by a dielectric material. The
      method relies on expanding the electromagnetic field (subtracted by one
      dimensional solutions of the layered media) in one-dimensional modes, where the
      expansion "coefficients" are functions satisfying two-dimensional Helmholtz
      equations. A system of equations is established on the boundary of the circular
      cylinder to solve the expansion "coefficients." The method effectively reduces
      the original three-dimensional scattering problem to a two-dimensional problem on
      the boundary of the cylinder. 

PMID- 24562029
TI  - Comparative analysis of discrete and continuous absorption weighting estimators
      used in Monte Carlo simulations of radiative transport in turbid media.
AB  - We examine the relative error of Monte Carlo simulations of radiative transport
      that employ two commonly used estimators that account for absorption differently,
      either discretely, at interaction points, or continuously, between interaction
      points. We provide a rigorous derivation of these discrete and continuous
      absorption weighting estimators within a stochastic model that we show to be
      equivalent to an analytic model, based on the radiative transport equation (RTE).
      We establish that both absorption weighting estimators are unbiased and,
      therefore, converge to the solution of the RTE. An analysis of spatially resolved
      reflectance predictions provided by these two estimators reveals no advantage to
      either in cases of highly scattering and highly anisotropic media. However, for
      moderate to highly absorbing media or isotropically scattering media, the
      discrete estimator provides smaller errors at proximal source locations while the
      continuous estimator provides smaller errors at distal locations. The origin of
      these differing variance characteristics can be understood through examination of
      the distribution of exiting photon weights. 

PMID- 24562031
TI  - Scattering of electromagnetic radiation by three-dimensional periodic arrays of
      identical particles.
AB  - The generalized multiparticle Mie-solution (GMM), a Lorenz-Mie-type rigorous
      theory for the scattering of a monochromatic plane wave by an arbitrary
      configuration of nonintersecting scattering bodies, has lately been revisited and
      further developed. A recent progress is the initiation of a special version
      applied to one- and two-dimensional (1D and 2D) periodic arrays (PAs) of
      identical particles [J. Opt. Soc. Am. A30, 1053 (2013)]. As a continuous advance,
      the present work extends the initiative PA-type solution from 1D and 2D to the
      more involved three-dimensional (3D) regular arrays. Analytical formulations
      applicable to the 3D PAs are derived, including the special PA-type explicit
      expressions for cross sections of extinction, scattering, backscattering, and
      radiation pressure. The specific PA-version is a complement to the general
      formulation and solution process of the standard GMM. In either 1D and 2D or 3D
      cases, the newly devised PA-approach is capable of providing expeditiously
      theoretical predictions of radiative scattering characteristics for periodic
      structures consisting of a huge number of identical unit cells, which the general
      approach of the GMM is unable to handle in practical calculations, owing to
      excessive computing time and/or computer memory requirements. To illustrate
      practical applications, sample numerical solutions obtained via the PA-approach
      are shown for 3D PAs of finite lengths that have ~5*10(7) component particles,
      including structures having a rectangular opening. Also discussed is potential
      future work on the theory and its tests.

PMID- 24562030
TI  - Use of commercial off-the-shelf digital cameras for scientific data acquisition
      and scene-specific color calibration.
AB  - Commercial off-the-shelf digital cameras are inexpensive and easy-to-use
      instruments that can be used for quantitative scientific data acquisition if
      images are captured in raw format and processed so that they maintain a linear
      relationship with scene radiance. Here we describe the image-processing steps
      required for consistent data acquisition with color cameras. In addition, we
      present a method for scene-specific color calibration that increases the accuracy
      of color capture when a scene contains colors that are not well represented in
      the gamut of a standard color-calibration target. We demonstrate applications of
      the proposed methodology in the fields of biomedical engineering, artwork
      photography, perception science, marine biology, and underwater imaging. 

PMID- 24562032
TI  - Efficient implementation of B-spline modal method for lamellar gratings.
AB  - The B-spline modal method (BMM) as applied to lamellar gratings analysis is
      revisited, and a new implementation is presented. The main difference with our
      previous work is that we now take into account discontinuities by putting a
      spline with a degenerate knot on them. Our new approach is compared with other
      implementations of the BMM and is shown to be superior in terms of numerical
      convergence. 

PMID- 24562033
TI  - Open problems in color constancy: discussion.
AB  - This paper discusses a number of open problems in color constancy theory whose
      correct solution is a prerequisite for the theory of the phenomenon. Solutions
      employing suitable visually meaningful versus physically meaningful basis
      functions (principal components) are examined. In the former case the starting
      point is an estimate of the first derivative of the reflectance (illuminant),
      essential for defining color, instead of an estimate of the reflectance
      (illuminant), as in the latter. Conceptual consequences are discussed.
      Mathematical and physical constraints are identified. We compare the results of
      theories that do or do not ignore them. The following questions are considered.
      (1) Do unique solutions of the estimation problem exist everywhere in the object
      color solid belonging to the illuminant? (2) Are they physically meaningful,
      i.e., at least nonnegative? (3) Are they representative for reflectance and
      spectral distribution functions? (4) What role plays metamerism?

PMID- 24562035
TI  - Diffraction theory for azimuthally structured Fresnel zone plate.
AB  - A conventional Fresnel zone plate (FZP) consists of concentric rings with an
      alternating binary transmission of zero and one. In an azimuthally structured
      Fresnel zone plate (aFZP), the light transmission of the transparent zones is
      modulated in the azimuthal direction, too. The resulting structure is of interest
      for extreme ultraviolet and x-ray imaging, in particular, because of its improved
      mechanical stability as compared to the simple ring structure of an FZP. Here, we
      present an analysis of the optical performance of the aFZP based on scalar
      diffraction theory and show numerical results for the light distribution in the
      focal plane. These will be complemented by calculations of the optical transfer
      function. 

PMID- 24562034
TI  - Modeling lateral geniculate nucleus response with contrast gain control. Part 2:
      analysis.
AB  - Cope et al. [J. Opt. Soc. Am. A30, 2401 (2013)] proposed a class of models for
      lateral geniculate nucleus (LGN) ON-cell behavior consisting of a linear response
      with divisive normalization by local stimulus contrast. Here, we analyze a
      specific model with the linear response defined by a difference-of-Gaussians
      filter, and a circular Gaussian for the gain pool weighting function. For
      sinusoidal grating stimuli, the parameter region for bandpass behavior of the
      linear response is determined, and the gain control response is shown to act as a
      switch (changing from "off" to "on" with increasing spatial frequency). It is
      also shown that large gain pools stabilize the optimal spatial frequency of the
      total nonlinear response at a fixed value independent of contrast and stimulus
      magnitude. Under- and super-saturation, as well as contrast saturation, occur as
      typical effects of stimulus magnitude. For circular spot stimuli, it is shown
      that large gain pools stabilize the spot size that yields the maximum response.

PMID- 24562036
TI  - Tight focusing of quasi-cylindrically polarized beams.
AB  - Based on vectorial diffraction theory, tight focusing properties of quasi
      cylindrical polarized beams (QCPBs) composed of equal fan-shaped sectors with
      linear polarization are investigated. We find that, for quasi-radially polarized
      illumination, a weak azimuthal component emerges and the circular symmetry of
      focus is traded in when the total number of sector N is small, but when N>=8 it
      is approaching that of a perfect radially polarized beam with a deviation smaller
      than 5.3% and a ratio of maximum total intensity larger than 95.5%. Meanwhile,
      for quasi-azimuthal polarized illumination, although weak radial and longitudinal
      components emerge, it is also close to that of the perfect azimuthally polarized
      beam when N>=8 with deviation smaller than 5.3% and a ratio larger than 95.0%.
      These results not only reveal a deep understanding of the focusing properties of
      QCPBs, but also provide an important contribution toward optimization of the
      monolithic methods for generating vector beams. 

PMID- 24562037
TI  - Self-similarity in radial Walsh filters and axial intensity distributions in the
      far-field diffraction pattern.
AB  - Pupil plane filtering by radial Walsh filters is a convenient technique for
      tailoring the axial intensity distribution near the focal plane of a rotationally
      symmetric imaging system. Radial Walsh filters, derived from radial Walsh
      functions, form a set of orthogonal phase filters that take on values either 0 or
      pi phase, corresponding to +1 or -1 values of the radial Walsh functions over
      prespecified annular regions of the circular filter. Order of these filters is
      given by the number of zero-crossings, or equivalently phase transitions within
      the domain over which the set is defined. In general, radial Walsh filters are
      binary phase zone plates, each of them demonstrating distinct focusing
      characteristics. The set of radial Walsh filters can be classified into distinct
      groups, where the members of each group possess self-similar structures. Self
      similarity can also be observed in the corresponding axial intensity
      distributions. These observations provide valuable clues in tackling the inverse
      problem of synthesis of phase filter in accordance with prespecified axial
      intensity distributions. This paper reports our observations on self-similarity
      in radial Walsh filters of various orders and corresponding axial intensity
      distributions. 

PMID- 24562038
TI  - Highly resonant and directional optical nanoantennas.
AB  - Plasmonic nanoantennas permit many functional components for future generations
      of nanoscale optical devices. They have been intensively studied and means were
      devised to engineer their optical response. However, as a metal-based resonator,
      the low quality factor of a plasmonic antenna hinders its further applications.
      Here, we propose a novel design to improve the quality factor of a dipolar
      nanoantenna by combining it with plasmonic Bragg gratings. This specific antenna
      design can support extraordinary sharp resonances and highly directional
      emissivity. Therefore, it promises to achieve many novel applications, e.g., in
      the field of cavity quantum electrodynamics where the strong coupling regime for
      light and matter comes in reach. 

PMID- 24562039
TI  - Full-phase photon-counting double-random-phase encryption.
AB  - We investigate a full-phase-based photon-counting double-random-phase encryption
      (PC-DRPE) method. A PC technique is applied during the encryption process,
      creating sparse images. The statistical distribution of the PC decrypted data for
      full-phase encoding and amplitude-phase encoding are derived, and their
      statistical parameters are used for authentication. The performance of the full
      phase PC-DRPE is compared with the amplitude-based PC-DRPE method. The PC
      decrypted images make it difficult to visually authenticate the input image;
      however, advanced correlation filters can be used to authenticate the decrypted
      images given the correct keys. Initial computational simulations show that the
      full-phase PC-DRPE has the potential to require fewer photons for authentication
      than the amplitude-based PC-DRPE. 

PMID- 24562040
TI  - Mathematical modeling of Fabry-Perot resonators: I. Complex-variable analysis by
      uniformly convergent partial-fraction expansion.
AB  - In the first part of a two-part study on the equivalent-circuit representation of
      any given Fabry-Perot resonator (FPR) that supports, by nature, infinitely many
      resonance modes, the complex-variable pole-zero structure of its scattering
      coefficients is extensively analyzed in general terms through partial-fraction
      expansion based on a corollary to Mittag-Leffler's theorem for meromorphic
      functions. By finding the right offset constant in the expansion from the theory,
      we present two sets of uniformly converging series of partial fractions for the
      two scattering coefficients. We compare quality of convergence between the two
      series sets and find that a set obtained by the fraction-reciprocated reflection
      coefficient for the FPR is relatively better than the other one, which is
      fortunate for the subsequent work in the second part. 

PMID- 24562041
TI  - Mathematical modeling of Fabry-Perot resonators: II. Uniformly converging
      multimode equivalent-circuit models.
AB  - Based on complex-variable analysis of a Fabry-Perot resonator as a multimode
      nonsymmetric two-port waveguide device, two versions of equivalent-circuit
      configurations are presented: Starting from a renewed study on single-mode two
      pole circuits, we develop two respective multimode equivalent circuits of an
      almost identical configuration: one for the reflection coefficient and the other
      for the pass-through transmission coefficient. In the mathematics language of
      complex-variable analysis, the two models successfully "approximate" the two
      scattering coefficients through two "uniformly converging" partial-fraction
      series expansions. 

PMID- 24562042
TI  - Wide-baseline stereo matching based on the line intersection context for real
      time workspace modeling.
AB  - Line matching in widely separated views is challenging because of large
      perspective distortion and violation of the planarity assumption in local
      regions. We introduce a novel method of wide-baseline image matching based on the
      coplanar line intersections for poorly textured and/or nonplanar structured
      scenes. The local areas of the coplanar line pairs are normalized into canonical
      frames by rectifying the coplanar line pairs to be orthogonal. Then, the 3D
      interpretation of the intersection context of the coplanar line pairs helps to
      match the nonplanar local regions. Furthermore, for calibrated stereo cameras, we
      propose a matching criterion based on 3D planar homography to improve the
      matching accuracy while reconstructing most likely physically existing planar
      patches. Experimental results demonstrate the effectiveness of the proposed
      method for real-world scenes. 

PMID- 24562043
TI  - Color representation and interpretation of special effect coatings.
AB  - A representation of the color gamut of special effect coatings is proposed and
      shown for six different samples, whose colors were calculated from spectral
      bidirectional reflectance distribution function (BRDF) measurements at different
      geometries. The most important characteristic of the proposed representation is
      that it allows a straightforward understanding of the color shift to be done both
      in terms of conventional irradiation and viewing angles and in terms of flake
      based parameters. A different line was proposed to assess the color shift of
      special effect coatings on a*,b*-diagrams: the absorption line. Similar to
      interference and aspecular lines (constant aspecular and irradiation angles,
      respectively), an absorption line is the locus of calculated color coordinates
      from measurement geometries with a fixed bistatic angle. The advantages of using
      the absorption lines to characterize the contributions to the spectral BRDF of
      the scattering at the absorption pigments and the reflection at interference
      pigments for different geometries are shown. 

PMID- 24562044
TI  - Wavefronts, caustic, ronchigram, and null ronchigrating of a plane wave refracted
      by an axicon lens.
AB  - The aim of this work is threefold: first we obtain analytical expressions for the
      wavefront train and the caustic associated with the refraction of a plane
      wavefront by an axicon lens, second we describe the structure of the ronchigram
      when the ronchiruling is placed at the flat surface of the axicon and the screen
      is placed at different relative positions to the caustic region, and third we
      describe in detail the structure of the null ronchigrating for this system; that
      is, we obtain the grating such that when it is placed at the flat surface of the
      axicon its associated pattern, at a given plane perpendicular to the optical
      axis, is a set of parallel fringes. We find that the caustic has only one branch,
      which is a segment of a line along the optical axis; the ronchigram exhibits self
      intersecting fringes when the screen is placed at the caustic region, and the
      null ronchigrating exhibits closed loop rulings if we want to obtain its
      associated pattern at the caustic region. 

PMID- 24562045
TI  - Excitotoxic stimulation of brain microslices as an in vitro model of stroke.
AB  - Examining molecular mechanisms involved in neuropathological conditions, such as
      ischemic stroke, can be difficult when using whole animal systems. As such,
      primary or 'neuronal-like' cell culture systems are commonly utilized. While
      these systems are relatively easy to work with, and are useful model systems in
      which various functional outcomes (such as cell death) can be readily quantified,
      the examined outcomes and pathways in cultured immature neurons (such as
      excitotoxicity-mediated cell death pathways) are not necessarily the same as
      those observed in mature brain, or in intact tissue. Therefore, there is the need
      to develop models in which cellular mechanisms in mature neural tissue can be
      examined. We have developed an in vitro technique that can be used to investigate
      a variety of molecular pathways in intact nervous tissue. The technique described
      herein utilizes rat cortical tissue, but this technique can be adapted to use
      tissue from a variety of species (such as mouse, rabbit, guinea pig, and chicken)
      or brain regions (for example, hippocampus, striatum, etc.). Additionally, a
      variety of stimulations/treatments can be used (for example, excitotoxic,
      administration of inhibitors, etc.). In conclusion, the brain slice model
      described herein can be used to examine a variety of molecular mechanisms
      involved in excitotoxicity-mediated brain injury.

PMID- 24562046
TI  - A limited sampling model to estimate exposure to lenalidomide in multiple myeloma
      patients.
AB  - BACKGROUND: The aim of this study was to develop a model able to predict the area
      under the lenalidomide plasma concentration-time curve (AUC) in multiple myeloma
      (MM) patients using a limited sampling strategy. METHODS: Forty-six hospitalized
      Japanese MM patients (25 men and 21 women) participated in this study. On days 3
      10 of lenalidomide therapy, whole-blood samples were collected just before oral
      lenalidomide administration, and 1, 2, 4, 8, 12, and 24 hours thereafter. Plasma
      concentrations of lenalidomide were analyzed using liquid chromatography-tandem
      mass spectrometry. RESULTS: The AUC0-24 predicted from a single lenalidomide
      plasma concentration measured 8 hours after the administration (C8h) showed the
      highest correlation with the measured AUC0-24 of lenalidomide (AUC0-24 = 13.0 *
      C8h + 1305.0; r = 0.832). To enhance the correlation between the predicted and
      the actual AUC0-24 of lenalidomide, we included information regarding
      lenalidomide elimination by entering creatinine clearance (CCr) data in the
      predictive formula of lenalidomide AUC0-24. Predicting the AUC0-24 of
      lenalidomide using data from 2 time points, C0h and C4h, along with CCr data
      further strengthened the correlation with the measured AUC0-24 of lenalidomide
      [AUC0-24 = 37.1 * C0h + 6.4 * C4h - 32.1 * CCr + 3265.6; r = 0.842]. CONCLUSIONS:
      The AUC0-24 of lenalidomide can be predicted using plasma concentrations measured
      at only 2 time points, C0h and C4h, in combination with CCr. Our study also
      suggests that the limited sampling strategy approach might help to identify
      patients with renal function impairment and who, despite dose adjustments,
      accumulate the drug, leading to a high AUC.

PMID- 24562048
TI  - Crystal structure and microstructural changes of molybdenum nitrides traced
      during catalytic reaction by in situ X-ray diffraction studies.
AB  - X-ray diffraction was used to study changes in the crystal structure and
      microstructure of molybdenum nitrides during ammonia decomposition. In addition,
      electron microscopy was employed to analyse morphological changes of the nitrides
      caused by the catalytic reaction. Molybdenum nitride catalysts (MoxNy) were
      prepared via high temperature ammonolysis of molybdenum oxide (MoO3) at 650 
      degrees C and 800  degrees C. The materials are nanocrystalline and highly
      porous, the samples produced at 650  degrees C still contain the partly reduced
      precursor (MoO2). In situ X-ray diffraction studies performed on a laboratory
      instrument equipped with a catalysis reaction chamber reveal significant
      compositional and structural changes taking place during the reaction. Ball
      milling, known to enhance the activity of catalysts, has a deleterious effect on
      the molybdenum nitride specimens: it gives an initial boost due to the reduction
      of size and increase in dislocation content, but it also favours the formation of
      the less active hexagonal MoN. 

PMID- 24562047
TI  - Lacosamide serum concentrations in adult patients with epilepsy: the influence of
      gender, age, dose, and concomitant antiepileptic drugs.
AB  - OBJECTIVE: Lacosamide (LCM), a new antiepileptic drug (AED) approved as
      adjunctive therapy for the treatment of patients with partial-onset seizures, has
      limited pharmacokinetic and drug interaction data. The main objectives of the
      present study were to investigate the effects of dose, age, gender, and hepatic
      enzyme-inducing AEDs on the pharmacokinetics of LCM as assessed by steady state
      serum LCM values. METHODS: An LCM AED therapeutic drug monitoring database was
      analyzed with regard to LCM serum concentrations and other relevant patient and
      AED drug information. One hundred twenty eight sera were identified. These were
      collected from 68 women and 61 men aged 19-66 years, who were prescribed a median
      LCM dose of 300 mg (range 50-600 mg). RESULTS: Serum LCM concentrations were
      observed in the following main groupings: LCM monotherapy (n = 5), LCM with
      nonenzyme-inducing AEDs (n = 50), LCM with enzyme-inducing AEDs (n = 49), LCM
      with valproic acid (n = 20), and LCM with enzyme-inducing AEDs plus valproic acid
      (n = 4). Analysis of variance showed a correlation of dose with LCM
      concentrations (r = 0.53, P < 0.001), and women had statistically higher mean LCM
      concentration than did men, 37.2 +/- 23.6 versus 26.8 +/- 12.9 MUmol/L (P =
      0.001). Serum LCM concentrations were significantly lower (P = 0.002) in the
      enzyme-inducing AED group (carbamazepine and phenytoin) compared with the LCM
      monotherapy group and the nonenzyme-inducing group, 23.5 +/- 11.0, 34.5 +/- 7.7,
      and 32.7 +/- 17.9 MUmol/L, respectively. CONCLUSIONS: Serum LCM concentrations
      increased dose dependently, were age independent, and were higher in women
      compared with men. Carbamazepine and phenytoin can significantly decrease serum
      LCM concentrations, probably via induction of LCM metabolism.

PMID- 24562049
TI  - Controlled fabrication of porous double-walled TiO2 nanotubes via ultraviolet
      assisted anodization.
AB  - Double-walled TiO2 nanotubes with porous wall morphologies are fabricated by
      anodization under ultraviolet (UV) irradiation. TiO2 formed by anodization of Ti
      is activated to generate electrons and holes by UV and the anodization process is
      influenced by the photo-generated charges. As a consequence, morphologies of the
      fabricated TiO2 nanotubes can be adjusted by controlling the UV illumination.
      Double-walled TiO2 nanotubes or single-walled nanotubes can be selectively formed
      by switching on/off the UV illumination. The thickness of the inner and outer
      walls of the double-walled nanotubes can be tailored by changing the UV power.
      Due to their larger surface areas compared to single-walled nanotubes, the porous
      double-walled nanotubes exhibit an enhanced photo-degradation rate for methylene
      blue (MB). The mechanism of the porous double-walled TiO2 nanotubes is proposed
      based on the photoactive semiconducting property of the as-growing TiO2 nanotubes
      under UV. 

PMID- 24562050
TI  - A unique cutaneous presentation of Burkitt lymphoma.
AB  - Few reports of cutaneous Burkitt lymphoma exist in the literature. Here, the
      authors describe the case of a human immunodeficiency virus-positive individual
      with the rare diagnosis of cutaneous Burkitt lymphoma. Three weeks before the
      development of his cutaneous lesions, the patient experienced bilateral lower
      extremity paralysis, and an epidural mass was found. Bone marrow biopsy findings
      and serum protein electrophoresis seemed consistent with multiple myeloma. The
      visible appearance of the skin lesions raised concern for cutaneous involvement
      by myeloma; however, the skin biopsy showed morphological and immunohistochemical
      features of Burkitt lymphoma. In this case report, the authors discuss the
      histopathologic findings of the cutaneous lesions in consideration with the bone
      marrow biopsy findings.

PMID- 24562051
TI  - Specific cutaneous involvement in Whipple disease.
AB  - Cutaneous lesions in Whipple disease (WD) are infrequent, and the histological
      findings are usually nonspecific. Specific cutaneous lesions have rarely been
      described and usually involve the subcutaneous fat. We report a patient diagnosed
      with WD, who developed multiple small subcutaneous nodules after antibiotic
      treatment was administered. In addition to septal panniculitis, the cutaneous
      biopsy showed a mild granulomatous dermal reaction with PAS-positive macrophages
      characteristic of WD. A positive polymerase chain reaction in the cutaneous
      sample confirmed the presence of Tropheryma whipplei in the skin.
      Dermatopathologists should be aware that not only subcutaneous lesions but also
      dermal lesions may exhibit specific findings of WD.

PMID- 24562052
TI  - Molecular cloning and expression of the gene for G protein alpha subunit induced
      by bisphenol A in marine polychaete Perinereis aibuhitensis.
AB  - A G protein alpha subunit gene named Pa Galpha was isolated from the marine
      polychaete Perinereis aibuhitensis. The full-length cDNA of Pa Galpha was 1832 bp
      and contained a 205 bp 5' untranslated region (5'UTR), a 565 bp 3' UTR and a 1062
      bp open reading frame encoding 353 amino acid residues. The deduced protein
      sequence of Pa Galpha showed 73% homology with the Galpha protein of Dipolydora
      quadrilobata. Tissue-specific expression induced by exposure to bisphenol A (BPA)
      in P. aibuhitensis was detected by real-time PCR, which showed BPA induced
      expression of the Pa Galpha gene, and the level of transcription was related
      positively to the concentration of BPA and the length of exposure time. With
      increasing concentration of BPA and length of exposure time, the level of mRNA
      transcription was raised gradually, but the level of increasing expression of Pa
      Galpha mRNA induced by exposure to BPA varied significantly among different
      tissues.

PMID- 24562053
TI  - Polychlorinated biphenyls and organochlorine pesticides in human milk samples
      from two regions in Croatia.
AB  - We analyzed 20 polychlorinated biphenyls (PCBs) and seven organochlorine
      pesticides (OCPs) in milk samples collected during 2009-2011 from primiparae
      living in two different regions in Croatia. p,p'-DDE is the dominant
      organochlorine pesticide. alpha-HCH/gamma-HCH and p,p'-DDE/p,p'-DDT ratios
      indicate that there is fresh input of gamma-HCH in investigated population on
      both locations, while this is not applicable to p,p'-DDT. The PCB profile was
      dominated by higher chlorinated congeners. Non-ortho PCB congeners which have the
      highest TEF values were not detected in any of individual samples. Toxic
      equivalents for mono-ortho substituted PCB congeners indicated higher exposure to
      toxic PCBs in Zadar, but estimated daily intakes for both locations indicate that
      infants consuming mother's milk are not at risk of adverse effects caused by PCBs
      and OCPs. Our study builds on the previous research of human milk samples
      collected in Zagreb and reveals that over 10-year period, levels of investigated
      organochlorine compounds decreased significantly. 

PMID- 24562054
TI  - Triclocarban-induced change in intracellular Ca2+ level in rat thymocytes:
      cytometric analysis with Fluo-3 under Zn2+-free conditions.
AB  - Triclocarban (TCC) is an antimicrobial used in personal hygiene products. Recent
      health concerns arose after TCC was detected in the blood of human subjects who
      showered with soap containing TCC. In this study, the effect of TCC on
      intracellular Ca(2+) concentration in rat thymocytes was examined using Fluo-3,
      an indicator of intracellular Ca(2+). TCC at concentrations ranging from 0.1 MUM
      to 3 MUM increased intracellular Ca(2+) concentration biphasically: first by
      releasing Ca(2+) from intracellular Ca(2+) stores and then inducing Ca(2+) influx
      through store-operated Ca(2+) channels. The threshold TCC concentration to
      increase intracellular Ca(2+) concentration in this study was lower than the
      maximum TCC concentrations reported in human blood samples. Therefore, we
      anticipate that TCC at concentrations reported in human blood samples might
      disturb intracellular Ca(2+) signaling in human lymphocytes.

PMID- 24562055
TI  - Chemical composition and bioactivities of flavonoids-rich extract from Davallia
      cylindrica Ching.
AB  - The flavonoids profiles and bioactivities of flavonoids-rich extract from
      Davallia cylindrica Ching were investigated. The total flavonoids content in D.
      cylindrica was determined as about 164.41 mg/g. The main flavonoids in D.
      cylindrica were tentatively identified as quercetin-3-O-rutinoside, quercetin 7-O
      glucoside, quercetin 7-O-glucoside, kaempferol 3-O-rutinoside, and quercitrin by
      UV and ESI-MS spectra. Flavonoids-rich extract (0.258 mg/ml) from D. cylindrica
      showed similar or higher free radical (O2(-), DPPH and ABTS) scavenging potential
      with that of rutin (0.25 mg/ml). The reducing power of flavonoids-rich extract
      (0.258 mg/ml) was slightly stronger than that of 0.25mg/ml rutin. The flavonoids
      extract from D. cylindrica exhibited cytotoxic effects on A549 cells. It
      exhibited a dose-dependent inhibition against acetylcholinesterase.

PMID- 24562056
TI  - Toxic effects of zearalenone on oxidative stress, inflammatory cytokines,
      biochemical and pathological changes induced by this toxin in the kidney of
      pregnant rats.
AB  - An experiment was conducted to determine the toxic effects of zearalenone (ZEN)
      on oxidative stress, inflammatory cytokines, biochemical and pathological changes
      in the kidney of pregnant rats, and to explore the possible mechanism in ZEN
      induced kidney damage. The rats were fed a normal diet treated with 0.3, 48.5,
      97.6 or 146 mg/kg ZEN in feed on gestation days (GDs) 0 through 7, and then all
      the rats were fed with a normal diet on GDs 8 through 20. The results showed that
      ZEN induced kidney dysfunction, oxidative damage, pathological changes and
      increased mRNA and protein expression of TLR4 and inflammatory cytokines in
      kidney in dose-dependent manner. The results indicated that ZEN caused kidney
      damage of pregnant rats and TLR4-mediated inflammatory reactions signal pathway
      was one of the mechanisms of ZEN mediated toxicity in kidney.

PMID- 24562057
TI  - Studies on the effect of sodium arsenate on the enzymes of carbohydrate
      metabolism, brush border membrane, and oxidative stress in the rat kidney.
AB  - Arsenic is an environmental pollutant and its contamination in drinking water
      poses serious world wide environmental health threats. It produces multiple
      adverse effects in various tissues, including the kidney. However, biochemical
      mechanism and renal response to its toxic insult are not completely elucidated.
      We hypothesized that sodium arsenate (ARS) induces oxidative stress and alters
      the structure and metabolic functions of kidney. Male Wistar rats were
      administered ARS (10 mg/kg body weight/day), intraperitoneally daily for 10 days.
      ARS administration increased blood urea nitrogen, serum creatinine, cholesterol,
      glucose, and phospholipids but decreased inorganic phosphate, indicating kidney
      toxicity. The activity of brush border membrane (BBM) enzymes significantly
      lowered in both cortex and medulla. Activity of hexokinase, lactate
      dehydrogenase, glucose-6-phosphate dehydrogenases, and NADP-malic enzyme
      significantly increased whereas malate dehydrogenase, glucose-6-phosphatase, and
      fructose 1,6 bis phosphatase decreased by ARS exposure. The activity of
      superoxide dismutase, GSH-peroxidase, and catalase were selectively altered in
      renal tissues along with an increase in lipid peroxidation. The present results
      indicated that ARS induced oxidative stress caused severe renal damage that
      resulted in altered levels of carbohydrate metabolism and BBM enzymes.

PMID- 24562059
TI  - Rolandic epilepsy has little effect on adult life 30 years later: a population
      based study.
AB  - OBJECTIVE: To establish the adult social outcome for childhood-onset rolandic
      epilepsy. METHODS: Patients with medication-treated rolandic epilepsy were
      identified from the Nova Scotia prospective population-based cohort of childhood
      onset epilepsy. Epilepsy onset was in 1977-1985 and follow-up was in 2010-2013
      with chart review plus structured telephone interview for those older than 21
      years. RESULTS: Forty-two children developed rolandic epilepsy (6% of 692
      incident epilepsy cases in the cohort). Thirty-two (76%) were contacted when they
      were older than 21 years. Epilepsy onset averaged 7.7 +/- 2.3 years, follow-up
      29.5 +/- 2.8 years, and final age 37 +/- 3.4 years. All had epilepsy remission
      and were off antiepileptic drug treatment for 21.4 +/- 6.6 years. There were 2
      minor injuries from seizures and only 1 death (from a snowmobile accident).
      Overall, 41% had >= 1 of 7 adverse social outcomes, 6 had 1, 4 had 2, and 3 had
      >= 3. These were failure to complete high school (n = 7), pregnancy outside of a
      stable relationship (<6 months) (n = 7), depression or other psychiatric
      diagnosis (n = 3), unemployment (n = 1), living alone (n = 5), never in a
      romantic relationship >3 months (n = 1), and poverty (n = 2). Those who did not
      complete high school were more likely to have parents with low academic
      achievement and/or low income (p < 0.02). By comparison, rates of >= 1 adverse
      social outcomes for other epilepsies with normal intelligence from this cohort
      varied from 62% to 76%. CONCLUSIONS: The adult social outcome for children with
      rolandic epilepsy is remarkably better than for those with other major epilepsies
      and normal intelligence.

PMID- 24562058
TI  - ALS2 mutations: juvenile amyotrophic lateral sclerosis and generalized dystonia.
AB  - OBJECTIVE: To determine the genetic etiology in 2 consanguineous families who
      presented a novel phenotype of autosomal recessive juvenile amyotrophic lateral
      sclerosis associated with generalized dystonia. METHODS: A combination of
      homozygosity mapping and whole-exome sequencing in the first family and Sanger
      sequencing of candidate genes in the second family were used. RESULTS: Both
      families were found to have homozygous loss-of-function mutations in the
      amyotrophic lateral sclerosis 2 (juvenile) (ALS2) gene. CONCLUSIONS: We report
      generalized dystonia and cerebellar signs in association with ALS2-related
      disease. We suggest that the ALS2 gene should be screened for mutations in
      patients who present with a similar phenotype.

PMID- 24562060
TI  - Recurrence of ICH after resumption of anticoagulation with VK antagonists:
      CHIRONE study.
AB  - OBJECTIVE: To evaluate the risk of recurrent intracranial hemorrhage (ICH) in
      patients on vitamin K antagonists (VKAs) after a first episode of ICH. METHODS:
      The Cerebral Haemorrhage in patients Restarting Oral Anticoagulant Therapy
      (CHIRONE) Study collected data of patients eligible for the study from the
      database of 27 centers affiliated with the Italian Federation of Anticoagulation
      Clinics. RESULTS: We enrolled 267 patients (163 male, median age 73.9 years) who
      had received VKA anticoagulation after an ICH event. During the total period of
      follow-up (778 patient-years), ICH recurred in 20 patients (7.5%; rate 2.56 * 100
      patient-years) at a median time of 16.5 months, and was fatal in 5 patients (25%;
      rate 0.4 * 100 patient-years). Male sex, hypertension, prosthetic valves,
      previous ischemic stroke, renal failure, cancer, and spontaneous events were
      associated with the risk of recurrence, though none of them in isolation reached
      statistical significance. More than one-third of spontaneous recurrences occurred
      in patients with a posttraumatic index event. CONCLUSIONS: Our results show that
      patients with a history of ICH carry a significant risk of recurrent ICH when
      treated with VKA anticoagulation. The risk is also present, though to a lower
      degree, in patients with previous posttraumatic events. All patients with a
      history of ICH require a careful evaluation of their thromboembolic risk to
      estimate the net clinical benefit of (re)starting anticoagulation with VKAs.

PMID- 24562061
TI  - Restarting anticoagulation after intracranial hemorrhage: a risky decision with
      no recipe.

PMID- 24562062
TI  - High baseline BDNF serum levels and early psychopathological improvement are
      predictive of treatment outcome in major depression.
AB  - RATIONALE: Major depressive disorder has been associated with low serum levels of
      brain-derived neurotrophic factor (sBDNF), which is functionally involved in
      neuroplasticity. Although sBDNF levels tend to normalize following
      psychopathological improvement with antidepressant treatment, it is unclear how
      closely sBDNF changes are associated with treatment outcome. OBJECTIVES: To
      examine whether baseline sBDNF or early changes in sBDNF are predictive of
      response to therapy. METHODS: Twenty-five patients with major depressive disorder
      underwent standardized treatment with duloxetine. Severity of depression,
      measured by the Hamilton Depression Rating Scale, and sBDNF were assessed at
      baseline, and after 1, 2, and 6 weeks of treatment. Therapy outcome after 6 weeks
      was defined as response (>=50 % reduction in baseline Hamilton Depression Rating
      score) and remission (Hamilton Depression Rating score <8). The predictive values
      for treatment outcome of baseline sBDNF, and early (i.e., <=2 weeks) changes in
      sBDNF and Hamilton Depression Rating score were also assessed. RESULTS: At
      baseline, sBDNF correlated with Hamilton Depression Rating scores. Treatment
      response was associated with a higher baseline sBDNF concentration, and a greater
      Hamilton Depression Rating score reduction after 1 and 2 weeks. A greater early
      rise in sBDNF correlated with a decreased early Hamilton Depression Rating score
      reduction. CONCLUSIONS: Even though higher baseline sBDNF levels are associated
      with more severe depression, they may reflect an increased capacity to respond to
      treatment. In contrast, changes in sBDNF over the full course of treatment are
      not associated with psychopathological improvement.

PMID- 24562063
TI  - Random-ratio schedules produce greater demand for i.v. drug administration than
      fixed-ratio schedules in rhesus monkeys.
AB  - RATIONALE: Organisms emit more responses when food is provided according to
      random as compared with fixed schedules of reinforcement. Similarly, many human
      behaviors deemed compulsive are maintained on variable schedules (e.g.,
      gambling). If greater amounts of behavior are maintained by drugs of abuse when
      earned according to variably reinforced schedules, this would suggest that
      excessive drug-taking behavior may be due in part to the nature of drug
      availability. OBJECTIVES: The aim was to determine whether random schedules of
      contingent intravenous drug delivery would produce more responding than similarly
      priced fixed schedules. METHODS: Six rhesus macaque subjects responded to produce
      cocaine (0.003-0.03 mg/kg/inj), remifentanil (0.01-1.0 MUg/kg/inj), or ketamine
      (0.01-0.1 mg/kg/inj) according to either fixed or random ratio requirements that
      increased systematically across sessions. Demand curves were generated with the
      most effective dose of each drug and compared across drug and schedule type.
      RESULTS: Cocaine and remifentanil maintained higher levels and rates of
      responding when earned according to random-ratio schedules as compared with fixed
      ratio schedules. This difference was most pronounced when drugs were available at
      high unit prices. Differences in responding across the schedule types generated
      by ketamine-a lesser-valued reinforcer-were qualitatively similar but smaller in
      magnitude. CONCLUSIONS: The current study provides a systematic replication
      across reinforcer type demonstrating that drugs delivered after a random number
      of responses generate more behavior than those delivered according to a fixed
      schedule. The variable nature of the availability of drugs of abuse-particularly
      those that are scarce or expensive-may be a contributing factor to excessive drug
      intake by humans. This effect is most likely to be observed when more highly
      demanded (reinforcing) drugs are being consumed.

PMID- 24562065
TI  - Analysis of hematopoiesis dynamics in residents of Techa riverside villages
      chronically exposed to nonuniform radiation: modeling approach.
AB  - A profound approach to the analysis of clinical data on the dynamics of major
      hematopoietic lineages (granulocytopoietic, thrombocytopoietic, and
      erythrocytopoietic systems) in chronically irradiated humans is proposed. It is
      based on recently developed mathematical models of these systems in humans, which
      enable one to study and interpret clinical hematological data. The developed
      approach is applied to the analysis of statistically processed clinical data,
      which were obtained under hematological examinations of residents of Techa
      riverside villages. These people were exposed to chronic irradiation with varying
      dose rate due to the radioactive contamination of the river basin by the Mayak
      Production Association. In the course of modeling studies, the relationship
      between the dynamics of aforementioned systems in examined individuals and the
      variation of chronic exposure dose rate over the considered period of time is
      revealed. It is found that the models are capable of reproducing common
      regularities and peculiarities of the dynamics of systems on hand, including the
      decreased stationary levels of blood cell concentrations during the period of
      maximum radiation exposure, the recovery processes during the period of decrease
      of exposure dose rate, and the prevalence of younger bone marrow
      granulocytopoietic cells over more mature ones during the entire period. The
      mechanisms of such effects of chronic irradiation on the hematopoietic lineages
      are revealed on the basis of modeling studies. All this testifies to the
      efficiency of employment of the developed models in the analysis, investigation,
      and prediction of effects of chronic irradiation on human hematopoietic system. 

PMID- 24562066
TI  - Cancer risk from low dose radiation depends directly on the organ mass in a
      general model of radiation-induced cancer risk.
AB  - Current methods of evaluating radiation-induced cancer risk depend on the organ
      dose but not explicitly on extensive quantities such as the organ mass. However,
      at the same organ dose, one may expect the larger number of cells in a larger
      organ to lead to a higher cancer risk. Here the author introduces organ- and
      radiation type-specific cell cancer risk coefficients and obtains analytical
      relations between cancer risk and the radiation environment, which contains the
      dependence of cancer risk on organ masses. The excess cancer risk induced by low
      dose radiation for an organ is shown to be directly proportional to the organ
      mass. Therefore the total excess risk for all solid cancers depends directly on
      organ masses and consequently on body weight or size. This method is also being
      compared with three existing methods of evaluating the radiation-induced cancer
      risk, and special cases where this formulation matches each method are
      demonstrated. The results suggest that the direct dependence of cancer risk on
      organ masses needs to be checked against existing epidemiological data and, if
      verified, should be included in the methodology for the evaluation of radiation
      induced cancer risk, in particular the individual risk. This dependence is also
      expected to affect the cancer risk transport from one population group to another
      that is different in organ mass, body weight or height. 

PMID- 24562067
TI  - Estimation of external radiation dose to caregivers of patients treated with
      radioiodine after thyroidectomy.
AB  - Due to the remarkable increase in thyroid cancer cases, the number of patients
      treated with radioiodine (I) shows a sharply increasing trend in recent years.
      Accordingly, radiation exposure of other people, particularly caregivers or
      comforters, after release of patients from hospitals is getting more attention
      than ever. In the present study, empirical equations are proposed for estimation
      of doses to caregivers. Only patients administered with therapeutic amounts of
      131I after thyroidectomy were considered. External radiation doses to 70
      caregivers or family members were measured using thermoluminescence dosimeters
      (TLDs). The mean, external, effective dose to caregivers, during a nursing period
      of 5-9 d after patient quarantine for 3-4 d in the hospital, was 0.12 +/- 0.10
      mSv. This is only 2.5% of the dose limit recommended by the International
      Commission on Radiological Protection for caregivers. By analyzing those
      individual doses to the caregivers, values of a factor affecting caregiver doses,
      K, are obtained for use in estimation of caregivers' doses. The factor reflects
      the degree of engagement of the caregiver to the patient, and hence it is named
      the "engagement factor." The mean value of the engagement factor in this study
      was 1.3 +/- 0.88. With the help of the engagement factor, the total external dose
      to a caregiver can be estimated as 1.1 * Q0 * e-0.05(Tr) mSv, where Q0 is the
      administered activity of 131I (GBq) and T(r) is the patient's release time (h)
      after admistration of radioiodine. Based on the dose estimation model developed
      in this study, by comparing the cost of extended quarantine against that incurred
      by release of the patient, including the burden of radiation exposure of
      caregivers or family members, the reasonableness of current quarantine periods
      was revisited. It was found that the dichotomous policy (i.e., hospitalizing
      patients administered 131I over 1.1 GBq for a period of 3-4 d compared with
      treating other patients administered below 1.1 GBq as outpatients) is
      unjustifiable; this is particularly true for those treated with a few GBq. Based
      upon the dose estimation model presented herein, tables suggesting an appropriate
      quarantine period depending upon the activity of the administered 131I are
      provided for use as reference in deciding when to release patients treated with
      therapy levels of 131I after thyroidectomy.

PMID- 24562064
TI  - Persistent reduction of cocaine seeking by pharmacological manipulation of
      adenosine A1 and A 2A receptors during extinction training in rats.
AB  - RATIONALE: Adenosine receptor stimulation and blockade have been shown to
      modulate a variety of cocaine-related behaviors. OBJECTIVES: These studies
      identify the direct effects of adenosine receptor stimulation on cocaine seeking
      during extinction training and the persistent effects on subsequent reinstatement
      to cocaine seeking. METHODS: Rats self-administered cocaine on a fixed ratio one
      schedule in daily sessions over 3 weeks. Following a 1-week withdrawal, the
      direct effects of adenosine receptor modulation were tested by administering the
      adenosine A1 receptor agonist, N(6)-cyclopentyladenosine (CPA, 0.03 and 0.1
      mg/kg), the adenosine A2A agonist, CGS 21680 (0.03 and 0.1 mg/kg), the
      presynaptic adenosine A2A receptor antagonist, SCH 442416 (0.3, 1, and 3 mg/kg),
      or vehicle prior to each of six daily extinction sessions. The persistent effects
      of adenosine receptor modulation during extinction training were subsequently
      tested on reinstatement to cocaine seeking induced by cues, cocaine, and the
      dopamine D2 receptor agonist, quinpirole. RESULTS: All doses of CPA and CGS 21680
      impaired initial extinction responding; however, only CPA treatment during
      extinction produced persistent impairment in subsequent cocaine- and quinpirole
      induced seeking. Dissociating CPA treatment from extinction did not alter
      extinction responding or subsequent reinstatement. Administration of SCH 442416
      had no direct effects on extinction responding but produced dose-dependent
      persistent impairment of cocaine- and quinpirole-induced seeking. CONCLUSIONS:
      These findings demonstrate that adenosine A1 or A2A receptor stimulation directly
      impair extinction responding. Interestingly, adenosine A1 receptor stimulation or
      presynaptic adenosine A2A receptor blockade during extinction produces lasting
      changes in relapse susceptibility.

PMID- 24562068
TI  - The cumulative risk of multiple CT exposures using two different methods.
AB  - The aim of this study was to compare the summing method (A) with the complement
      method (B) for calculating the cumulative lifetime-attributable-risk (LAR(tot))
      of tumor incidence and mortality of multiple CT exposures. Method A defines
      LAR(tot) as the summation of the risk of each separate exposure. Method B was
      defined as the complement of the probability of inducing no cancer in N separate
      exposures. The risk of each separate exposure was estimated using dose, gender,
      and age at exposure (BEIR VII phase 2). Both methods were compared in a
      simulation and applied to a database of 11,884 patients exposed to multiple CTs.
      The relative difference between the methods was defined as DeltaP%. Simulation
      confirmed that Method A always overestimates LAR(tot). DeltaP% was proportional
      to the dose per exposure and the number of exposures. The differences between
      Methods A and B were small. Average LAR(tot) of tumor incidence was 0.140%
      (Method A) and 0.139% (Method B) with maxima of 5.70% and 5.56%, respectively.
      Average LAR(tot) of mortality was 0.085% for both methods, with maxima of 2.20%
      and 2.18%, respectively. DeltaP% was highest (2.43%) for a female patient (3-y
      old) exposed to eight recurrent scans and a cumulative dose of 144 mSv. Although
      Method B is more accurate, both methods can be used to estimate the cumulative
      risk of multiple CT exposures. These results have to be interpreted, however, in
      the perspective of the uncertainties in the cancer risk model, which have been
      estimated at a factor of 2 or 3.

PMID- 24562069
TI  - Study of the counting efficiency of a WBC setup by using a computational 3D human
      body library in sitting position based on polygonal mesh surfaces.
AB  - A realistic computational 3D human body library, called MaMP and FeMP (Male and
      Female Mesh Phantoms), based on polygonal mesh surface geometry, has been created
      to be used for numerical calibration of the whole body counter (WBC) system of
      the nuclear power plant (NPP) in Doel, Belgium. The main objective was to create
      flexible computational models varying in gender, body height, and mass for
      studying the morphology-induced variation of the detector counting efficiency
      (CE) and reducing the measurement uncertainties. First, the counting room and an
      HPGe detector were modeled using MCNPX (Monte Carlo radiation transport code).
      The validation of the model was carried out for different sample-detector
      geometries with point sources and a physical phantom. Second, CE values were
      calculated for a total of 36 different mesh phantoms in a seated position using
      the validated Monte Carlo model. This paper reports on the validation process of
      the in vivo whole body system and the CE calculated for different body heights
      and weights. The results reveal that the CE is strongly dependent on the
      individual body shape, size, and gender and may vary by a factor of 1.5 to 3
      depending on the morphology aspects of the individual to be measured. 

PMID- 24562071
TI  - A new understanding of multiple-pulsed laser-induced retinal injury thresholds.
AB  - Laser safety standards committees have struggled for years to formulate
      adequately a sound method for treating repetitive-pulse laser exposures. Safety
      standards for lamps and LEDs have ignored this issue because averaged irradiance
      appeared to treat the issue adequately for large retinal image sizes and skin
      exposures. Several authors have recently questioned the current approach of three
      test conditions (i.e., limiting single-pulse exposure, average irradiance, and a
      single-pulse-reduction factor) as still insufficient to treat pulses of unequal
      energies or certain pulse groupings. Schulmeister et al. employed thermal
      modeling to show that a total-on-time pulse (TOTP) rule was conservative. Lund
      further developed the approach of probability summation proposed by Menendez et
      al. to explain pulse-additivity, whereby additivity is the result of an
      increasing probability of detecting injury with multiple pulse exposures. This
      latter argument relates the increase in detection probability to the slope of the
      probit curve for the threshold studies. Since the uncertainty in the threshold
      for producing an ophthalmoscopically detectable minimal visible lesion (MVL) is
      large for retinal exposure to a collimated laser beam, safety committees
      traditionally applied large risk reduction factors ("safety factors") of one
      order of magnitude when deriving intrabeam, "point-source" exposure limits. This
      reduction factor took into account the probability of visually detecting the low
      contrast lesion among other factors. The reduction factor is smaller for large
      spot sizes where these difficulties are quite reduced. Thus the N-0.25 reduction
      factor may result from the difficulties in detecting the lesion. Recent studies
      on repetitive pulse exposures in both animal and in vitro (retinal explant)
      models support this interpretation of the available data.

PMID- 24562070
TI  - Radiation safety considerations for the use of 223RaCl2 DE in men with castration
      resistant prostate cancer.
AB  - The majority of patients with late stage castration-resistant prostate cancer
      (CRPC) develop bone metastases that often result in significant bone pain.
      Therapeutic palliation strategies can delay or prevent skeletal complications and
      may prolong survival. An alpha-particle based therapy, radium-223 dichloride
      (223RaCl2), has been developed that delivers highly localized effects in target
      areas and likely reduces toxicity to adjacent healthy tissue, particularly bone
      marrow. Radiation safety aspects were evaluated for a single comprehensive cancer
      center clinical phase 1, open-label, single ascending-dose study for three
      cohorts at 50, 100, or 200 kBq kg-1 body weight. Ten patients received
      administrations, and six patients completed the study with 1 y follow-up. Dose
      rates from patients administered 223Ra dichloride were typically less than 2 MUSv
      h-1 MBq-1 on contact and averaged 0.02 MUSv h-1 MBq-1 at 1 m immediately
      following administration. Removal was primarily by fecal excretion, and whole
      body effective half-lives were highly dependent upon fecal compartment transfer,
      ranging from 2.5-11.4 d. Radium-223 is safe and straightforward to administer
      using conventional nuclear medicine equipment. For this clinical study, few
      radiation protection limitations were recommended post-therapy based on facility
      evaluations. Specific precautions are dependent on local regulatory authority
      guidance. Subsequent studies have demonstrated significantly improved overall
      survival and very low toxicity, suggesting that 223Ra may provide a new standard
      of care for patients with CRPC and bone metastases.

PMID- 24562072
TI  - Role of dicentric analysis in an overarching biodosimetry strategy for use
      following a nuclear detonation in an urban environment.
AB  - In the moments immediately following a nuclear detonation, casualties with a
      variety of injuries including trauma, burns, radiation exposure, and combined
      injuries would require immediate assistance. Accurate and timely radiation dose
      assessments, based on patient history and laboratory testing, are absolutely
      critical to support adequately the triage and treatment of those affected. This
      capability is also essential for ensuring the proper allocation of scarce
      resources and will support longitudinal evaluation of radiation-exposed
      individuals and populations. To maximize saving lives, casualties must be
      systematically triaged to determine what medical interventions are needed, the
      nature of those interventions, and who requires intervention immediately. In the
      National Strategy for Improving the Response and Recovery for an Improvised
      Nuclear Device (IND) Attack, the U.S. Department of Homeland Security recognized
      laboratory capacity for radiation biodosimetry as having a significant gap for
      performing mass radiation dose assessment. The anticipated demand for radiation
      biodosimetry exceeds its supply, and this gap is partly linked to the limited
      number and analytical complexity of laboratory methods for determining radiation
      doses within patients. The dicentric assay is a key component of a cytogenetic
      biodosimetry response asset, as it has the necessary sensitivity and specificity
      for assessing medically significant radiation doses. To address these shortfalls,
      the authors have developed a multimodal strategy to expand dicentric assay
      capacity. This strategy includes the development of an internet-based
      cytogenetics network that would address immediately the labor intensive burden of
      the dicentric chromosome assay by increasing the number of skilled personnel to
      conduct the analysis. An additional option that will require more time includes
      improving surge capabilities by combining resources available within the
      country's 150 clinical cytogenetics laboratories. Key to this intermediate term
      effort is the fact that geneticists and technicians may be experts in matters
      related to identifying chromosomal abnormalities related to genetic disorders,
      but they are not familiar with dosimetry for which training and retraining will
      be required. Finally, long-term options are presented to improve capacity focus
      on ways to automate parts of the dicentric chromosome assay method. 

PMID- 24562073
TI  - Radiation safety considerations in proton aperture disposal.
AB  - Beam shaping in scattered and uniform scanned proton beam therapy (PBT) is made
      commonly by brass apertures. Due to proton interactions, these devices become
      radioactive and could pose safety issues and radiation hazards. Nearly 2,000
      patient-specific devices per year are used at Indiana University Cyclotron
      Operations (IUCO) and IU Health Proton Therapy Center (IUHPTC); these devices
      require proper guidelines for disposal. IUCO practice has been to store these
      apertures for at least 4 mo to allow for safe transfer to recycling contractors.
      The devices require decay in two staged secure locations, including at least 4 mo
      in a separate building, at which point half are ready for disposal. At 6 mo, 20
      30% of apertures require further storage. This process requires significant space
      and manpower and should be considered in the design process for new clinical
      facilities. More widespread adoption of pencil beam or spot scanning nozzles may
      obviate this issue, as apertures then will no longer be necessary. 

PMID- 24562077
TI  - CTER-rapid estimation of CTF parameters with error assessment.
AB  - In structural electron microscopy, the accurate estimation of the Contrast
      Transfer Function (CTF) parameters, particularly defocus and astigmatism, is of
      utmost importance for both initial evaluation of micrograph quality and for
      subsequent structure determination. Due to increases in the rate of data
      collection on modern microscopes equipped with new generation cameras, it is also
      important that the CTF estimation can be done rapidly and with minimal user
      intervention. Finally, in order to minimize the necessity for manual screening of
      the micrographs by a user it is necessary to provide an assessment of the errors
      of fitted parameters values. In this work we introduce CTER, a CTF parameters
      estimation method distinguished by its computational efficiency. The efficiency
      of the method makes it suitable for high-throughput EM data collection, and
      enables the use of a statistical resampling technique, bootstrap, that yields
      standard deviations of estimated defocus and astigmatism amplitude and angle,
      thus facilitating the automation of the process of screening out inferior
      micrograph data. Furthermore, CTER also outputs the spatial frequency limit
      imposed by reciprocal space aliasing of the discrete form of the CTF and the
      finite window size. We demonstrate the efficiency and accuracy of CTER using a
      data set collected on a 300kV Tecnai Polara (FEI) using the K2 Summit DED camera
      in super-resolution counting mode. Using CTER we obtained a structure of the 80S
      ribosome whose large subunit had a resolution of 4.03A without, and 3.85A with,
      inclusion of astigmatism parameters. 

PMID- 24562088
TI  - Attention Feedback Awareness and Control Training (A-FACT): experimental test of
      a novel intervention paradigm targeting attentional bias.
AB  - We present an experimental investigation of a novel intervention paradigm
      targeting attentional bias - Attention Feedback Awareness and Control Training (A
      FACT). A-FACT is grounded in the novel hypothesis that training awareness of
      (biased) attentional allocation will lead to greater self-regulatory control of
      attention and thereby ameliorate attentional bias and its maladaptive sequelae.
      To do so, A-FACT delivers computerized, personalized, real-time feedback
      regarding a person's (biased) allocation of attention concurrent with its
      expression. In a randomized control experimental design, we tested A-FACT
      relative to an active placebo control condition among anxious adults (N=40, 52.5%
      women, M(SD)=24.3(4) years old). We found that relative to the placebo control
      condition, A-FACT led to: (a) reduced levels of attentional bias to threat; (b)
      (non-significantly) lower rate of behavioral avoidance of exposure to an
      anxiogenic stressor; and (c) faster rate of emotional recovery following the
      stressor. The findings are discussed with respect to the novelty and significance
      of the proposed conceptual perspective, methodology, and intervention paradigm
      targeting attentional bias.

PMID- 24562089
TI  - White matter disorders of childhood.

PMID- 24562087
TI  - A pilot randomized controlled trial of Dialectical Behavior Therapy with and
      without the Dialectical Behavior Therapy Prolonged Exposure protocol for suicidal
      and self-injuring women with borderline personality disorder and PTSD.
AB  - OBJECTIVE: This study evaluates the efficacy of integrating PTSD treatment into
      Dialectical Behavior Therapy (DBT) for women with borderline personality
      disorder, PTSD, and intentional self-injury. METHODS: Participants were
      randomized to DBT (n=9) or DBT with the DBT Prolonged Exposure (DBT PE) protocol
      (n=17) and assessed at 4-month intervals during the treatment year and 3-months
      post-treatment. RESULTS: Treatment expectancies, satisfaction, and completion did
      not differ by condition. In DBT+DBT PE, the DBT PE protocol was feasible to
      implement for a majority of treatment completers. Compared to DBT, DBT+DBT PE led
      to larger and more stable improvements in PTSD and doubled the remission rate
      among treatment completers (80% vs. 40%). Patients who completed the DBT PE
      protocol were 2.4 times less likely to attempt suicide and 1.5 times less likely
      to self-injure than those in DBT. Among treatment completers, moderate to large
      effect sizes favored DBT+DBT PE for dissociation, trauma-related guilt
      cognitions, shame, anxiety, depression, and global functioning. CONCLUSIONS: DBT
      with the DBT PE protocol is feasible, acceptable, and safe to administer, and may
      lead to larger improvements in PTSD, intentional self-injury, and other outcomes
      than DBT alone. The findings require replication in a larger sample.

PMID- 24562090
TI  - The basis of inborn errors of metabolism for neuroradiologists.
AB  - Although relatively common together, inborn errors of metabolism (IEM) are
      individually rare, which makes difficult for most neuroradiologists to accumulate
      significant experience on these conditions. To facilitate the diagnostic
      approach, several schemes based on clinical, biochemical, genetic, and
      neuroimaging criteria have been proposed. Neuroimaging techniques have a great
      potential to improve diagnostic accuracy in as well as follow-up and management
      of the patients with an IEM. This article aimed to provide a nonexhaustive review
      of some basic information related to genetic conditions such as pattern of
      inheritance, penetrance, variable expressivity, genotype, phenotype and to
      provide information on how to classify, investigate, diagnose, and treat IEM
      besides highlighting some findings that would aid neuroradiologists to improve
      the diagnostic accuracy of imaging techniques, particularly magnetic resonance
      imaging. 

PMID- 24562091
TI  - Inherited white matter disorders of childhood: a magnetic resonance imaging-based
      pattern recognition approach.
AB  - Inherited white matter disorders of childhood (WMDC) refer to a broad group of
      progressive inherited disorders that exclusively or predominantly affect myelin
      formation and/or maintenance. They are often in the form of neurological
      deficits, developmental delay, or frank encephalopathy and are difficult to
      diagnose clinically. The imaging diagnostic approach for the WMDC is difficult
      and demands knowledge of neuroimaging features, age of onset of the disease,
      genetic pattern, and recognition of the most important clinical findings.
      Unfortunately, the variability and evolving patterns of imaging findings,
      combined with the continual discovery of new metabolic diseases, make
      establishing a diagnosis difficult for radiologists who lack experience in the
      imaging of suspected metabolic diseases. The goal of this article was to present
      a structured neuroimaging approach to inherited WMDC based on the most
      discriminating magnetic resonance imaging features as the starting point to
      create a list of the most probable diagnoses. 

PMID- 24562092
TI  - Idiopathic inflammatory demyelinating disorders of the central nervous system in
      children.
AB  - Idiopathic inflammatory demyelinating disorders of the central nervous system
      usually present with a typical morphologic pattern in adults, with multiple
      sclerosis as the predominant disorder. However, the variety of disorders in
      children has an odd range of features that have piqued the interest of
      researchers. Information concerning this group of diseases, both in vivo and in
      different age groups, has particularly progressed with the advent of magnetic
      resonance imaging in the last few decades. In this article, we provide an
      overview of the applicability of imaging for idiopathic inflammatory
      demyelinating disorders of the central nervous system in children. In addition to
      pediatric multiple sclerosis, this review addresses other related disorders, such
      as acute disseminated encephalomyelitis, pediatric neuromyelitis optica,
      recurrent optic neuritis, and relapsing transverse myelitis. 

PMID- 24562093
TI  - Imaging features of acquired pediatric metabolic and toxic white matter
      disorders.
AB  - Acquired white matter abnormalities in children may be due to a broad spectrum of
      disorders, with the most significant related to metabolic and toxic etiologies.
      Recognition of the imaging appearance of neonatal hypoglycemia, nonketotic
      hyperglycemia, hyperammonemia, hepatic encephalopathy, and central pontine
      myelinolysis (CPM) is essential because prompt correction of the underlying
      metabolic abnormality may limit and, in some cases, reverse the cerebral damage.
      Toxic leukoencephalopathies encompass disorders caused by iatrogenic
      administration of pharmacologic agents and radiation therapy, poisoning by
      household substances, and recreational drug use. Although medication-induced
      leukoencephalopathies often show a propensity for reversibility of clinical and
      radiologic findings upon discontinuation of the offending substance, recreational
      drugs may cause white matter toxicity that often portends a poorer prognosis. Our
      discussion focuses on the clinical aspects, pathophysiological mechanisms, and
      imaging features of commonly encountered acquired metabolic and toxic
      leukoencephalopathies in the pediatric population. 

PMID- 24562094
TI  - Advanced magnetic resonance imaging techniques in the evaluation of pediatric
      white matter diseases.
AB  - This article aimed to describe the technical principles and clinical application
      of advanced magnetic resonance imaging techniques for the assessment of white
      matter diseases. The following techniques are going to be discussed:
      magnetization transfer, proton magnetic resonance spectroscopy, diffusion
      weighted imaging, diffusion tensor imaging, as well as perfusion and
      postprocessing techniques such as tract-based spatial statistics. These
      techniques allow a better understanding of the physiopathology of the white
      matter diseases as well as have a significant impact on the definition of the
      differential diagnosis and treatment options. 

PMID- 24562096
TI  - Hydrogen evolution from water using Ag(x)Cu(1-x)GaSe2 photocathodes under visible
      light.
AB  - Photoelectrochemical (PEC) water splitting using CuGaSe2 (CGSe) thin film
      photocathodes modified by partial substitution of Cu with Ag was investigated.
      The AgxCu1-xGaSe2 (ACGSe) thin films were deposited onto Mo-coated soda-lime
      glass substrates by means of co-evaporation using a molecular beam epitaxy (MBE)
      system. The valence band maximum (VBM) potential of ACGSe is deeper than that of
      CGSe, and its grain size is greatly increased compared to that of CGSe. A Pt and
      CdS modified ACGSe electrode (Pt/CdS/ACGSe) with a Ag/(Cu + Ag) ratio of about 5%
      showed a cathodic photocurrent of 8.1 mA cm(-2) at 0 VRHE and an onset potential
      of 0.70 VRHE (defined as a cathodic photocurrent of 0.05 mA cm(-2)) under
      simulated sunlight in a 0.1 M Na2SO4 solution (pH 9.5). Moreover, Pt/CdS/ACGSe
      exhibited a stable cathodic photocurrent for over 55 h, with no clear decrease. 

PMID- 24562095
TI  - Use of label-free optical biosensors to detect modulation of potassium channels
      by G-protein coupled receptors.
AB  - Ion channels control the electrical properties of neurons and other excitable
      cell types by selectively allowing ions to flow through the plasma membrane(1).
      To regulate neuronal excitability, the biophysical properties of ion channels are
      modified by signaling proteins and molecules, which often bind to the channels
      themselves to form a heteromeric channel complex(2,3). Traditional assays
      examining the interaction between channels and regulatory proteins require
      exogenous labels that can potentially alter the protein's behavior and decrease
      the physiological relevance of the target, while providing little information on
      the time course of interactions in living cells. Optical biosensors, such as the
      X-BODY Biosciences BIND Scanner system, use a novel label-free technology,
      resonance wavelength grating (RWG) optical biosensors, to detect changes in
      resonant reflected light near the biosensor. This assay allows the detection of
      the relative change in mass within the bottom portion of living cells adherent to
      the biosensor surface resulting from ligand induced changes in cell adhesion and
      spreading, toxicity, proliferation, and changes in protein-protein interactions
      near the plasma membrane. RWG optical biosensors have been used to detect changes
      in mass near the plasma membrane of cells following activation of G protein
      coupled receptors (GPCRs), receptor tyrosine kinases, and other cell surface
      receptors. Ligand-induced changes in ion channel-protein interactions can also be
      studied using this assay. In this paper, we will describe the experimental
      procedure used to detect the modulation of Slack-B sodium-activated potassium
      (KNa) channels by GPCRs. 

PMID- 24562099
TI  - Effect of operating parameters on the removal of bone cement by a sawing process.
AB  - The number of total knee arthroplasty revision surgeries is increasing each year,
      driven by the wide availability and general acceptance of the procedure
      accompanied by an aging population of implants. Metal implants are often secured
      to the tibial plateau by a mantle of poly(methyl methacrylate) bone cement.
      During revision surgery, a power oscillating saw is used to remove bone cement
      while preparing the boney bed. Presently, there are no published studies on the
      mechanics of bone cement removal by a sawing process. The aim of this research
      was to quantify the effect of blade speed and applied thrust force on the
      volumetric cutting rate of bone cement. A custom reciprocating saw with variable
      stroke length was used to conduct a three-factor design of experiments. Two
      levels, without center-points, were sufficient to model the effect of stroke
      length (6.75, 10.13 mm), thrust force (11, 19 N), and reciprocating speed in
      strokes per minute (6000, 8000 SPM) on cutting rate. The results indicate that
      each of the three parameters had a significant impact on cutting rate (p <
      0.001), with a linear relationship between both force and cutting rate (r = 0.98)
      and blade speed and cutting rate (r = 0.98). For the parameters considered,
      increasing the reciprocating speed had the most significant effect on cutting
      rate. For example, while holding force and stroke length constant (11 N, 10.13
      mm), an increase in speed from 6000 to 8000 SPM nearly doubled the cutting rate
      of bone cement. A cutting rate model was developed by regression analysis of the
      experimental data and validated through additional experiments. The model has
      applications in haptic feedback for surgical simulators to differentiate between
      the cutting rates of bone and bone cement during virtual training of resident
      surgeons. 

PMID- 24562100
TI  - Silica-based nanocomposites via reverse microemulsions: classifications,
      preparations, and applications.
AB  - Silica-based nanocomposites with amorphous silica as the matrix or carrier along
      with a functional component have been extensively investigated. These
      nanocomposites combine the advantages of both silica and the functional
      components, demonstrating great potential for various applications. To synthesize
      such composites, one of the most frequently used methods is reverse microemulsion
      due to its convenient control over the size, shape, and structures. The
      structures of the composites have a decisive significance for their properties
      and applications. In this review, we tried to categorize the silica-based
      nanocomposites via reverse microemulsions based on their structures, discussed
      the syntheses individually for each structure, summarized their applications, and
      made some perspectives based on the current progress of this field. 

PMID- 24562098
TI  - Using microfluidics chips for live imaging and study of injury responses in
      Drosophila larvae.
AB  - Live imaging is an important technique for studying cell biological processes,
      however this can be challenging in live animals. The translucent cuticle of the
      Drosophila larva makes it an attractive model organism for live imaging studies.
      However, an important challenge for live imaging techniques is to noninvasively
      immobilize and position an animal on the microscope. This protocol presents a
      simple and easy to use method for immobilizing and imaging Drosophila larvae on a
      polydimethylsiloxane (PDMS) microfluidic device, which we call the 'larva chip'.
      The larva chip is comprised of a snug-fitting PDMS microchamber that is attached
      to a thin glass coverslip, which, upon application of a vacuum via a syringe,
      immobilizes the animal and brings ventral structures such as the nerve cord,
      segmental nerves, and body wall muscles, within close proximity to the coverslip.
      This allows for high-resolution imaging, and importantly, avoids the use of
      anesthetics and chemicals, which facilitates the study of a broad range of
      physiological processes. Since larvae recover easily from the immobilization,
      they can be readily subjected to multiple imaging sessions. This allows for
      longitudinal studies over time courses ranging from hours to days. This protocol
      describes step-by-step how to prepare the chip and how to utilize the chip for
      live imaging of neuronal events in 3(rd) instar larvae. These events include the
      rapid transport of organelles in axons, calcium responses to injury, and time
      lapse studies of the trafficking of photo-convertible proteins over long
      distances and time scales. Another application of the chip is to study
      regenerative and degenerative responses to axonal injury, so the second part of
      this protocol describes a new and simple procedure for injuring axons within
      peripheral nerves by a segmental nerve crush. 

PMID- 24562101
TI  - Optimum measurement criteria for the axial derivative intensity used in transport
      of intensity-equation-based solvers.
AB  - For several years, scientific, industrial, and biological fields have benefited
      from knowledge of phase information, which allows for the revealing of hidden
      features of various objects. An alternative to interferometry is single-beam
      phase retrieval techniques that are based on the transport of intensity equation,
      which describes the relation between the axial derivative of the intensity and
      the phase distribution for a given plane in the Fresnel region. The estimation of
      the axial intensity derivative is obtained from a series of intensity
      measurements, where the accuracy is subject to an optimum separation between the
      measurement planes depending on the number of planes, the level of noise, and the
      actual object phase distribution. In this Letter, a quantitative analysis of the
      error in estimated axial derivative is carried out and a model is reported that
      describes the interdependence between these parameters. The results of this work
      allow for estimation of the optimum separation between measurement planes with
      minimal error in the axial derivative. 

PMID- 24562097
TI  - Interplay between circadian rhythm, time of the day and osmotic stress
      constraints in the regulation of the expression of a Solanum Double B-box gene.
AB  - BACKGROUND AND AIMS: Double B-box zinc finger (DBB) proteins are recently
      identified plant transcription regulators that participate in the response to
      sodium chloride-induced stress in arabidopsis plants. Little is known regarding
      their subcellular localization and expression patterns, particularly in relation
      to other osmotic constraints and the day/night cycle. This study investigated
      natural variations in the amount of a Solanum DBB protein, SsBBX24, during plant
      development, and also under various environmental constraints leading to cell
      dehydration in relation to the circadian clock and the time of day. METHODS:
      SsBBX24 transcript and protein abundance in various organs of phytotron-grown
      Solanum tuberosum and S. sogarandinum plants were investigated at different time
      points of the day and under various osmotic constraints. The intracellular
      location of SsBBX24 was determined by western blot analysis of subcellular
      fractions. KEY RESULTS: Western blot analysis of SsBBX24 protein revealed that it
      was located in the nucleus at the beginning of the light period and in the
      cytosol at the end, suggesting movement ('trafficking') during the light phase.
      SsBBX24 gene expression exhibited circadian cycling under control conditions,
      with the highest and lowest abundances of both transcript and protein occurring 8
      and 18 h after dawn, respectively. Exposing Solanum plants to low temperature,
      salinity and polyethylene glycol (PEG), but not to drought, disturbed the
      circadian regulation of SsBBX24 gene expression at the protein level. SsBBX24
      transcript and protein accumulated in Solanum plants in response to salt and PEG
      treatments, but not in response to low temperature or water deficit. Most
      interestingly, the time of the day modulated the magnitude of SsBBX24 expression
      in response to high salt concentration. CONCLUSIONS: The interplay between
      circadian rhythm and osmotic constraints in the regulation of the expression of a
      Solanum DBB transcriptional regulator is demonstrated. It is proposed that stress
      dependent, post-transcriptional mechanisms alter the regulation by the circadian
      clock of the amount of SsBBX24.

PMID- 24562103
TI  - Rolled-up TiO2 optical microcavities for telecom and visible photonics.
AB  - The fabrication of high-quality-factor polycrystalline TiO2 vertically rolled-up
      microcavities (VRUMs) by the controlled release of differentially strained TiO2
      bilayered nanomembranes, operating at both telecom and visible wavelengths, is
      reported. Optical characterization of these resonators reveals quality factors as
      high as 3.8*103 in the telecom wavelength range (1520-1570 nm) by interfacing a
      TiO2 VRUMs with a tapered optical fiber. In addition, a splitting in the
      fundamental modes is experimentally observed due to the broken rotational
      symmetry in our resonators. This mode splitting indicates coupling between
      clockwise and counterclockwise traveling whispering gallery modes of the VRUMs.
      Moreover, we show that our biocompatible rolled-up TiO2 resonators function at
      several positions along the tube, making them promising candidates for
      multiplexing and biosensing applications.

PMID- 24562102
TI  - Compact piezoelectric transducer fiber scanning probe for optical coherence
      tomography.
AB  - We developed a compact, optical fiber scanning piezoelectric transducer (PZT)
      probe for endoscopic and minimally invasive optical coherence tomography (OCT).
      Compared with previous forward-mount fiber designs, we present a reverse-mount
      design that achieves a shorter rigid length. The fiber was mounted at the
      proximal end of a quadruple PZT tube and scanned inside the hollow PZT tube to
      reduce the probe length. The fiber resonant frequency was 338 Hz using a 17-mm
      long fiber. A 0.9 mm fiber deflection was achieved with a driving amplitude of 35
      V. Using a GRIN lens-based optical design with a 1.3* magnification, a ~6 MUm
      spot was scanned over a 1.2 mm diameter field. The probe was encased in a metal
      hypodermic tube with a ~25 mm rigid length and covered with a 3.2 mm outer
      diameter (OD) plastic sheath. Imaging was performed with a swept source OCT
      system based on a Fourier domain modelocked laser (FDML) light source at a 240
      kHz axial scan rate and 8 MUm axial resolution (in air). En face OCT imaging of
      skin in vivo and human colon ex vivo was demonstrated.

PMID- 24562104
TI  - Lensless phase contrast microscopy based on multiwavelength Fresnel diffraction.
AB  - We demonstrate a compact, wide-field, quantitative phase contrast microscope that
      does not require lenses for image formation. High-resolution images are retrieved
      from Fresnel diffraction patterns recorded at multiple wavelengths, combined with
      a robust iterative phase retrieval algorithm. Quantitative phase contrast images
      of living cultured neurons are obtained with a transverse resolution of <2 MUm.
      Our system is well suited for high-resolution live cell imaging and provides a
      compact, cost-effective alternative to full-sized phase-contrast microscopes.

PMID- 24562105
TI  - 100 Tbit/s free-space data link enabled by three-dimensional multiplexing of
      orbital angular momentum, polarization, and wavelength.
AB  - We investigate the orthogonality of orbital angular momentum (OAM) with other
      multiplexing domains and present a free-space data link that uniquely combines
      OAM-, polarization-, and wavelength-division multiplexing. Specifically, we
      demonstrate the multiplexing/demultiplexing of 1008 data channels carried on 12
      OAM beams, 2 polarizations, and 42 wavelengths. Each channel is encoded with 100
      Gbit/s quadrature phase-shift keying data, providing an aggregate capacity of
      100.8 Tbit/s (12*2*42*100 Gbit/s).

PMID- 24562106
TI  - Blind equalization for dual-polarization two-subcarrier coherent QPSK-OFDM
      signals.
AB  - Dual-polarization two-subcarrier coherent optical orthogonal frequency division
      multiplexing (CO-OFDM) transmission and reception is successfully demonstrated
      with blind equalization. A two-subcarrier quadrature phase shift keyed OFDM (QPSK
      OFDM) signal can be equalized as a 9-ary quadrature amplitude modulation signal
      in the time domain with the cascaded multimodulus algorithm equalization method.
      The nonlinear effect resistance and transmission distance can be enhanced
      compared with the traditional CO-OFDM transmission system based on frequency
      equalization with training sequence. 

PMID- 24562107
TI  - Pulse-width-tunable 0.7 W mode-locked Cr: forsterite laser.
AB  - A mode-locked chromium forsterite laser with output power in excess of 0.7 W, a
      central wavelength of 1.25 MUm, a pulse repetition rate of 29 MHz, and an output
      pulse-width-tunable from 40 to 200 fs is demonstrated. The dynamics behind the
      buildup of ultrashort light pulses in this laser is shown to involve spectral and
      temporal breathing due to the interplay of gain, Kerr nonlinearity, and
      dispersion effects. The pulse-width-tunable 1.25 MUm output delivered by the
      developed laser source suggests a powerful tool for nonlinear-optical bio-imaging
      and offers an advantageous front end for extreme-power laser technologies.

PMID- 24562108
TI  - Triple-clad large-pitch fibers for compact high-power pulsed fiber laser systems.
AB  - We present a novel ytterbium (Yb)-doped large-pitch fiber design with
      significantly increased pump absorption and higher energy storage/gain per unit
      length, which enables high-peak-power fiber laser systems with smaller
      footprints. Up to now index matching between core and surrounding material in
      microstructured fibers was achieved by co-doping the active core region with
      fluorine. Here we carry out the index matching by passively doping the cladding
      with germanium, thus raising its index of refraction. Hence, the fluorine in the
      core can be omitted, which leads to an effective increase of the core doping
      concentration, while detrimental effects such as photo-darkening and lifetime
      quenching are avoided by maintaining the bulk Yb concentration. Experiments and
      simulations show that a gain higher than 50 dB/m and an output average power
      higher than 100 W with excellent beam quality are feasible even with a fiber
      length of only 40 cm.

PMID- 24562109
TI  - Three-dimensional nanostructuring in YIG ferrite with femtosecond laser.
AB  - With the goal of creating magneto-optical devices, we demonstrated forming
      nanostructures inside a substrate of cerium-substituted yttrium iron garnet
      (Ce:YIG) by means of direct laser writing. Laser irradiation changed both the
      optical and magnetic properties of Ce:YIG. The measurements showed that the
      refractive index was increased by 0.015 (about 0.7% change) and the magnetization
      property was changed from hard to soft to decrease the coercivity. This
      technology enables the formation of 3-dimensional optical and magnetic
      nanostructures in YIG and will contribute to the development of novel devices for
      optical communication and photonic integration. 

PMID- 24562110
TI  - Uniform theoretical description of plasmon-induced transparency in plasmonic stub
      waveguide.
AB  - We investigate a classic analog of electromagnetically induced transparency (EIT)
      in a metal-dielectric-metal (MDM) bus waveguide coupled to two stub resonators. A
      uniform theoretical model, for both direct and indirect couplings between the two
      stubs, is established to study spectral features in the plasmonic stub waveguide,
      and the theoretical results agree well with the finite difference time domain
      simulations. Adjusting phase difference and coupling strength of the interaction,
      one can realize the EIT-like phenomena and achieve the required slow light
      effect. The theoretical results may provide a guideline for the control of light
      in highly integrated optical circuits. 

PMID- 24562111
TI  - Flexible generation of optical nonuniform bit-mapping signal based on InP
      transmitter module.
AB  - Flexible generation of an optical nonuniform bit-mapping signal based on an InP
      transmitter module is demonstrated. It can realize flexible bit mapping through
      the photonic modulation method, which can break the limitations of an electrical
      digital-to-analog convertor and field-programmable gate array. This module has
      potential to easily increase the signal rate or refine the granularity without
      electronics, which indicates it may be a future application to replace the
      traditional transmitter. The feasibility and performance of the proposed scheme
      are demonstrated in the experiment. 

PMID- 24562112
TI  - Secondary optical element design for intracorporeal LED illumination system.
AB  - In this Letter, we propose an intracorporeal illumination system for providing
      uniform and wide-field illumination during minimally invasive surgery. The
      illumination system is comprised of an Alexis wound retractor, a set of LEDs, and
      secondary optical elements (SOEs). The SOE was composed of a Fresnel lens and a
      total internal reflection lens, which was designed to improve the optical
      performance of the LED. The results of simulation demonstrate that the optical
      efficiency of each LED with an SOE could be increased from 33.6% to 82.9%. To
      avoid damage to human tissue by thermal effect, the number of LEDs with SOEs was
      optimized. The results indicate that our design to be applicable for practical
      surgery. 

PMID- 24562113
TI  - Nondestructive optical detection of monomer uptake in wood polymer composites.
AB  - A noninvasive method to assess the local monomer concentration within a wooden
      matrix, post monomer impregnation, by time-resolved diffuse optical spectroscopy
      is demonstrated. A data analysis technique for improving accuracy, which takes
      account of changes in the refractive index during the monomer uptake, has been
      employed. This technique can be potentially applied in the wood industry for the
      study of polymer composites as well as in cultural heritage science for
      noninvasively monitoring the penetration of chemical compounds used for
      consolidation or conservation purposes. 

PMID- 24562114
TI  - Optical nanofiber-based photonic crystal cavity.
AB  - We demonstrate the fabrication of photonic crystal (PhC) cavities on optical
      nanofibers using femtosecond laser ablation. PhC cavities with cavity lengths
      varying from 0.54 to 3.43 mm are fabricated by controlling the profile of the
      nanocrater array formed on the nanofiber. Such PhC cavities show high
      transmission of 87% for a finesse of 39. For higher finesse values from 150 to
      500, the transmission can still be maintained at 20%-25%. Due to the strong
      confinement of the field and the efficient coupling to single-mode optical
      fibers, such nanofiber-based PhC cavities may become an interface between quantum
      and classical networks.

PMID- 24562115
TI  - Generation of picosecond pulses directly from a 100 W, burst-mode, doping-managed
      Yb-doped fiber amplifier.
AB  - Burst-mode laser systems offer increased effectiveness in material processing
      while requiring lower individual pulse energies. Fiber amplifiers operating in
      this regime generate low powers in the order of 1 W. We present a Yb-doped fiber
      amplifier, utilizing doping management, that scales the average power up to 100
      W. The laser system produces bursts at 1 MHz, where each burst comprises 10
      pulses with 10 MUJ energy per pulse and is separated in time by 10 ns. The high
      burst repetition rate allows substantial simplification of the setup over
      previous demonstrations of burst-mode operation in fiber lasers. The total energy
      in each burst is 100 MUJ and the average power achieved within the burst is 1 kW.
      The pulse evolution in the final stage of amplification is initiated as self
      similar amplification, which is quickly altered as the pulse spectrum exceeds the
      gain bandwidth. By prechirping the pulses launched into the amplifier, 17 ps long
      pulses are generated without using external pulse compression. The peak power of
      the pulses is ~0.6 MW.

PMID- 24562116
TI  - Image cloning beyond diffraction based on coherent population trapping in a hot
      rubidium vapor.
AB  - Following recent theoretical predictions, we report on an experimental
      realization of image cloning beyond usual diffraction, through the coherent
      population trapping (CPT) effect in a hot rubidium vapor. In our experiment, an
      alphabet letter image was transferred from a coupling field to a probe field,
      based on the CPT effect. Furthermore, we demonstrate that the cloned probe field
      carrying the image is transmitted without the usual diffraction. To our best
      knowledge, this is the first experimental report about image cloning beyond
      diffraction. We believe this mechanism, based on CPT, has definite and important
      applications in image metrology, image processing, and biomedical imaging. 

PMID- 24562117
TI  - Quantitative Mueller matrix fluorescence spectroscopy for precancer detection.
AB  - Quantitative fluorescence spectroscopic Mueller matrix measurements from the
      connective tissue regions of human cervical tissue reveal intriguing fluorescence
      diattenuation and polarizance effects. Interestingly, the estimated fluorescence
      linear diattenuation and polarizance parameters were considerably reduced in the
      precancerous tissues as compared to the normal ones. These polarimetry effects of
      the autofluorescence were found to originate from anisotropically organized
      collagen molecular structures present in the connective tissues. Consequently,
      the reduction of the magnitude of these polarimetric parameters at higher grades
      of precancer was attributed to the loss of anisotropic organization of collagen,
      which was also confirmed by control experiments. These results indicate that
      fluorescence spectral diattenuation and polarizance parameters may serve as
      potentially useful diagnostic metrics. 

PMID- 24562118
TI  - Linear-in-wavenumber swept laser with an acousto-optic deflector for optical
      coherence tomography.
AB  - We report a novel linear-in-wavenumber (k-linear) swept laser source based on an
      acousto-optic deflector (AOD). The AOD-based optical filter includes an acousto
      optic deflector and a reflection grating. The laser may tune k linearly in
      wavenumber over time due to its appropriate configuration and is favorable for
      fast imaging because it avoids data resampling and recalibration, as are required
      in conventional swept source optical coherence tomography (SS-OCT). We achieved k
      linearity with Pearson's r correlation coefficients of 0.99995 without and
      0.99997 with optimization. The laser has a tuning range of 50 nm, a 3 dB swept
      range of 42 nm (FWHM), output power of 2.56 mW, 6 dB sensitivity roll-off depth
      of 0.941 mm, and central wavelength of 1064 nm at a scanning rate of ~20 kHz.
      Scanning rate as high as ~400 kHz is also achieved for this laser with the tuning
      range 49 nm, swept linearity of 0.99990, output power of 2.30 mW, and a 6 dB
      sensitivity roll-off depth 0.550 mm. SS-OCT imaging with linear-in-wavenumber
      swept laser is also demonstrated.

PMID- 24562119
TI  - Color tuning and thermal quenching of different sensitizer ion, Mn2+ or Ce3+,
      doped Ba2Mg(BO3)2:Eu2+ phosphor.
AB  - Ba2Mg(BO3)2:Eu2+ phosphors incorporated with two different sensitizers, Mn2+ or
      Ce3+, were prepared and their emission properties, especially for color purity
      and thermal stability, were investigated thoroughly. The overall emission
      property induced by the Eu2+ ion and the resultant thermal behavior were strongly
      dependent on the type of codoped sensitizer ions, Mn2+ or Ce3+. Intense red
      emission peaking at 620 nm was obtained upon 370 nm excitation of the Mn2+
      sensitized phosphor and the resultant light-emitting diode lamps using the given
      phosphor exhibited a more reddish emission with chromaticity coordinates of
      (0.602, 0.340). Thus, we can meet the purpose of illuminating elements by
      designing the proper chemical composition of the Eu2+-activated Ba2Mg(BO3)2
      phosphor using different sensitizers: a more reddish emitting Mn2+-sensitized one
      for backlight units and a bright yellow-emitting Ce3+-sensitized one for solid
      state lightings.

PMID- 24562120
TI  - Transverse electromagnetic modes in chiral negatively refractive fibers and a new
      type of space-division multiplexing.
AB  - We investigated theoretically chiral negatively refractive fibers that guide
      transverse electromagnetic modes. In this Letter, novel properties of such fibers
      are presented, including arbitrariness of modal field and arbitrarily scalable
      core radius. Based on these novel properties, we conceptually propose a new type
      of space-division multiplexing that uses different spatial positions of the core
      of such fascinating fibers as different data paths. 

PMID- 24562121
TI  - Extremely small polarization beam splitter based on a multimode interference
      coupler with a silicon hybrid plasmonic waveguide.
AB  - A novel polarization beam splitter (PBS) with an extremely small footprint is
      proposed based on a multimode interference (MMI) coupler with a silicon hybrid
      plasmonic waveguide. The MMI section, covered with a metal strip partially, is
      designed to achieve mirror imaging for TE polarization. On the other hand, for TM
      polarization, there is almost no MMI effect since the higher-order TM modes are
      hardly excited due to the hybrid plasmonic effect. With this design, the whole
      PBS including the 1.1 MUm long MMI section as well as the output section has a
      footprint as small as ~1.8 MUm*2.5 MUm. Besides, the fabrication process is
      simple since the waveguide dimension is relatively large (e.g., the input/output
      waveguides widths w >=300 nm and the MMI width w(MMI)=800 nm). Numerical
      simulations show that the designed PBS has a broad band of ~80 nm for an ER >10
      dB as well as a large fabrication tolerance to allow a silicon core width
      variation of -30 nm<Deltaw<50 nm and a metal strip width variation of -200
      nm<Deltaw(m)<0.

PMID- 24562122
TI  - Dissipative shock waves in all-normal-dispersion mode-locked fiber lasers.
AB  - We propose an interpretation of the pronounced "M" spectral shape that is a
      recurrent feature in all-normal-dispersion mode-locked fiber laser dynamics. Our
      interpretation involves shock wave formation regularized by dissipation, modeled
      by a modified Burgers equation. The large fringes appearing at the edges of the
      spectrum result from discontinuities in the spectral phase. 

PMID- 24562123
TI  - Mode-locked Nd-doped fiber laser at 930  nm.
AB  - We report on a passively mode-locked neodymium-doped oscillator featuring a W
      type fiber operating at 930 nm. Two different laser configurations with and
      without dispersion management are investigated to generate high-energy
      similaritons. Chirped pulses with 2.2 nJ energy that can be compressed to 126 fs
      are generated in the dispersion-managed cavity. The ANDI-fiber laser delivers
      parabolic pulses with 5.2 ps duration that can be compressed to 146 fs.

PMID- 24562124
TI  - Graphene-based tunable plasmonic Bragg reflector with a broad bandwidth.
AB  - We propose and numerically analyze a plasmonic Bragg reflector formed in a
      graphene waveguide. The results show that the graphene plasmonic Bragg reflector
      can produce a broadband stopband that can be tuned over a wide wavelength range
      by a small change in the Fermi energy level of graphene. By introducing a defect
      into the Bragg reflector, we can achieve a Fabry-Perot-like microcavity with a
      quality factor of 50 for the defect resonance mode formed in the stopband. The
      proposed Bragg reflector could be used as a broadband ultrafast tunable
      integrated filter and a broadband modulator. In addition, the defect microcavity
      may find applications in graphene-based resonators. 

PMID- 24562126
TI  - Fiber-laser-based noise-immune cavity-enhanced optical heterodyne molecular
      spectrometry incorporating an optical circulator.
AB  - To reduce the complexity of fiber-laser-based noise-immune cavity-enhanced
      optical heterodyne molecular spectrometry, a system incorporating a fiber-coupled
      optical circulator to deflect the cavity-reflected light for laser stabilization
      has been realized. Detection near the shot-noise limit has been demonstrated for
      both Doppler-broadened and sub-Doppler signals, yielding a lowest detectable
      absorption and optical phase shift of 2.2*10(-12)  cm(-1) and 4.0*10(-12)  cm(
      1), respectively, both for a 10 s integration time, where the former corresponds
      to a detection limit of C2H2 of 5 ppt.

PMID- 24562125
TI  - Correction of depth-dependent aberrations in 3D single-molecule localization and
      super-resolution microscopy.
AB  - Single-molecule switching based super-resolution microscopy techniques have been
      extended into three dimensions through various 3D single-molecule localization
      methods. However, the localization accuracy in z can be severely degraded by the
      presence of aberrations, particularly the spherical aberration introduced by the
      refractive index mismatch when imaging into an aqueous sample with an oil
      immersion objective. This aberration confines the imaging depth in most
      experiments to regions close to the coverslip. Here we show a method to obtain
      accurate, depth-dependent z calibrations by measuring the point spread function
      (PSF) at the coverslip surface, calculating the microscope pupil function through
      phase retrieval, and then computing the depth-dependent PSF with the addition of
      spherical aberrations. We demonstrate experimentally that this method can
      maintain z localization accuracy over a large range of imaging depths. Our super
      resolution images of a mammalian cell nucleus acquired between 0 and 2.5 MUm past
      the coverslip show that this method produces accurate z localizations even in the
      deepest focal plane.

PMID- 24562127
TI  - Coherence properties of Kerr frequency combs.
AB  - We use numerical simulations based on an extended Lugiato-Lefever equation (LLE)
      to investigate the stability properties of Kerr frequency combs generated in
      microresonators. In particular, we show that an ensemble average calculated over
      sequences of output fields separated by a fixed number of resonator roundtrips
      allows the coherence of Kerr combs to be quantified in terms of the complex
      degree of first-order coherence. We identify different regimes of comb coherence,
      linked to the solutions of the LLE. Our approach provides a practical and
      unambiguous way of assessing the stability of Kerr combs that is directly
      connected to an accessible experimental quantity. 

PMID- 24562128
TI  - Low-noise Brillouin laser on a chip at 1064 nm.
AB  - We demonstrate narrow-linewidth-stimulated Brillouin lasers at 1064 nm from ultra
      high-Q silica wedge disk resonators on silicon. Fundamental Schawlow-Townes
      frequency noise of the laser is on the order of 0.1 Hz2/Hz. The technical noise
      spectrum of the on-chip Brillouin laser is close to the thermodynamic noise limit
      of the resonator (thermorefractive noise) and is comparable to that of ultra
      narrow-linewidth Nd:YAG lasers. The relative intensity noise of the Brillouin
      laser also is reduced by using an intensity-stabilized pump laser. Finally, low
      noise microwave synthesis up to 32 GHz is demonstrated by heterodyne of first and
      third Brillouin Stokes lines from a single resonator.

PMID- 24562129
TI  - Circular-linear grating Talbot interferometry with moire Fresnel imaging for beam
      collimation.
AB  - The Talbot interferometer using different self-imaging structures is studied and
      applied for laser beam collimation. A circular-linear grating pair enables visual
      dynamic detection and computer moiregram analysis. Automatic single-frame
      processing is performed using a 2D continuous wavelet transform. Conducting
      moiregram imaging in the Fresnel field of a double-diffraction system is brought
      up to avoid using distortion-free objectives and simplify the experimental setup.
      Simulation and experimental results document the method properties and provide
      beautiful exemplification of the double-grating Fresnel diffraction theory
      developed earlier. 

PMID- 24562130
TI  - Low-loss and low-bend-sensitivity mid-infrared guidance in a hollow-core-photonic
      bandgap fiber.
AB  - Hollow-core-photonic-bandgap fiber, fabricated from high-purity synthetic silica,
      with a wide operating bandwidth between 3.1 and 3.7 MUm, is reported. A minimum
      attenuation of 0.13 dB/m is achieved through a 19-cell core design with a thin
      core wall surround. The loss is reduced further to 0.05 dB/m following a purging
      process to remove hydrogen chloride gas from the fiber-representing more than an
      order of magnitude loss reduction as compared to previously reported bandgap
      guiding fibers operating in the mid-infrared. The fiber also offers a low bend
      sensitivity of <0.25 dB per 5 cm diameter turn over a 300 nm bandwidth.
      Simulations are in good agreement with the achieved losses and indicate that a
      further loss reduction of more than a factor of 2 should be possible by enlarging
      the core using a 37-cell design.

PMID- 24562131
TI  - Nanostep height measurement via spatial mode projection.
AB  - We demonstrate an optical scheme for measuring the thickness of thin nanolayers
      with the use of light beam's spatial modes. The novelty in our scheme is the
      projection of the beam reflected by the sample onto a properly tailored spatial
      mode. In the experiment described below, we are able to measure a step height
      smaller than 10 nm, i.e., one-eightieth (1/80) of the wavelength with a standard
      error in the picometer scale. Since our scheme enhances the signal-to-noise
      ratio, which effectively increases the sensitivity of detection, the extension of
      this technique to the detection of subnanometric layer thicknesses is feasible.

PMID- 24562132
TI  - 1064  nm dispersive Raman spectroscopy of tissues with strong near-infrared
      autofluorescence.
AB  - Raman spectroscopy is an established technique for molecularly specific
      characterization of tissues. However, even with near-infrared (NIR) excitation,
      some tissues possess background autofluorescence, which can overwhelm Raman
      scattering. Here, we report collection of spectra from tissues with strong
      autofluorescence using a 1064 nm system with a high-throughput dispersive
      spectrometer and deep-cooled InGaAs array. Spectra collected at 1064 nm were
      compared with those collected at 785 nm in specimens from human breast, liver,
      and kidney. The results demonstrate superior performance at 1064 nm in the liver
      and kidney, where NIR autofluorescence is intense. The results indicate the
      feasibility of new biomedical applications for Raman spectroscopy at 1064 nm in
      tissues with strong autofluorescence.

PMID- 24562134
TI  - Artificial birefringent metallic planar structures for terahertz wave
      polarization manipulation.
AB  - We propose an artificial birefringent terahertz (THz) device constructed by
      subwavelength L-shaped hole arrays on a single metallic layer. This structure is
      able to work as a polarizer when the incident frequency is between the cut-off
      frequencies of two eigenmodes. When the incident wave is beyond cut-off
      frequencies of these two modes, it can be designed as an efficient half- or
      quarter-wave plate with extraordinary transmission properties. A big effective
      index difference from 0.254 to 0.768 is obtained using a subwavelength-thick
      planar structure, which can reduce the thickness of the device to one tenth of
      conventional quartz birefringent crystals for THz waves. 

PMID- 24562135
TI  - Optical free-space wavelength-division-multiplexing transport system.
AB  - An optical free-space wavelength-division-multiplexing (WDM) transport system
      employing vertical cavity surface emitting lasers and spatial light modulators
      with 16-quadrature amplitude modulation orthogonal frequency-division
      multiplexing modulating signals over a 17.5 m free-space link is proposed and
      demonstrated. With the help of a low-noise amplifier and data comparator, good
      bit error rate performance is obtained for each optical channel. Such an optical
      free-space WDM transport system would be attractive for providing services
      including data and telecommunication services.

PMID- 24562133
TI  - Two-photon injection of polaritons in semiconductor microstructures.
AB  - We experimentally demonstrate that two-photon pumping of "dark" excitons in
      quantum wells embedded in semiconductor microcavities can result in exciton
      polariton injection and photon lasing. In the case of a semiconductor micropillar
      pumped at half of the exciton frequency, we observe a clear threshold behavior,
      characteristic of the vertical cavity surface emitting laser transition. These
      results are interpreted in terms of stimulated emission of terahertz photons,
      which allows for conversion of "dark" excitons into exciton-polaritons. 

PMID- 24562136
TI  - Raman rogue waves in a partially mode-locked fiber laser.
AB  - We report on an experimental study of spectral fluctuations induced by
      intracavity Raman conversion in a passively partially mode-locked, all-normal
      dispersion fiber laser. Specifically, we use dispersive Fourier transformation to
      measure single-shot spectra of Raman-induced noise-like pulses, demonstrating
      that for low cavity gain values Raman emission is sporadic and follows rogue-wave
      like probability distributions, while a saturated regime with Gaussian statistics
      is obtained for high pump powers. Our experiments further reveal intracavity
      rogue waves originating from cascaded Raman dynamics. 

PMID- 24562137
TI  - Broadband pulse compression gratings with measured 99.7% diffraction efficiency.
AB  - We present experimental investigations of grating mirrors with high diffraction
      efficiencies exceeding 99.7% in the -1st order for TE polarization at a
      wavelength of 1060 nm, and exceeding a diffraction efficiency of 99% in the
      wavelength range from 1025 nm to at least 1070 nm. The total efficiency of a four
      pass compressor for chirped pulse amplification was >96%. The design,
      fabrication, and characterization of the fully dielectric grating mirrors are
      presented.

PMID- 24562138
TI  - Highly efficient and robust operation of Kerr-lens mode-locked Cr:LiSAF lasers
      using gain-matched output couplers.
AB  - We present efficient and robust Kerr-lens mode locking (KLM) of a diode-pumped
      Cr:LiSAF laser using a gain-matched output coupler (GMOC). An inexpensive,
      battery-powered 660 nm single-spatial-mode diode was used as the pump source.
      GMOC enhances the effective self-amplitude modulation depth by reducing the gain
      filtering effect in broadband KLM operation to provide significant improvement in
      efficiency and robustness. Pulsing can be initiated without careful cavity
      alignment and is sustained for hours. 13 fs pulses with an average power of 25 mW
      have been generated using only 120 mW of pump power. The corresponding pulse
      energy and peak power is 200 pJ and 15 kW for the 126 MHz repetition rate cavity.
      Optical-to-optical conversion efficiency of the system is 21%, which represents
      an order of magnitude improvement in reported efficiencies for such diode-pumped
      ultrashort-pulse KLM Cr:LiSAF lasers. The obtainable pulse width is currently
      limited by the dispersion bandwidth of the available optics and can be
      potentially reduced to below 7 fs.

PMID- 24562139
TI  - Efficient multiband absorber based on one-dimensional periodic metal-dielectric
      photonic crystal with a reflective substrate.
AB  - We propose an efficient multiband absorber comprised of a truncated, one
      dimensional periodic metal-dielectric photonic crystal and a reflective
      substrate. The reflective substrate is essentially an optically thick metallic
      film. Such a planar device is easier to fabricate compared to absorbers with
      complicated shapes. For a four-unit cell device, all four of the absorption peaks
      can be optimized with efficiencies higher than 95 percent. Moreover, those
      absorption peaks are insensitive to the polarization and incident angle. The
      influences of the geometrical parameters and the refractive index of the
      dielectric on the device performance also are discussed. Furthermore, we found
      that the number of absorption peaks within each photonic band precisely
      corresponds to the number of unit cells because the truncated photonic crystal
      lattices select resonant modes. We also show that the total absorption efficiency
      gradually increases when there are more periods of the metal-dielectric composite
      layer placed on top of the metallic substrate. We expect this work to have
      potential applications in solar energy harvesting and thermal emission tailoring.

PMID- 24562140
TI  - Ultra-low-loss CMOS-compatible waveguide crossing arrays based on multimode Bloch
      waves and imaginary coupling.
AB  - We experimentally demonstrate broadband waveguide crossing arrays showing
      ultralow loss of 0.0 4dB/crossing (0.9%) on average and converging to 0.033
      dB/crossing (0.075%) matching theory and cross-talk suppression over 35 dB in a
      CMOS-compatible geometry. The principle of operation is the tailored excitation
      of a low-loss spatial Bloch wave formed by matching the periodicity of the
      crossing array to the difference in propagation constants of the first- and third
      order TE-like modes of a multimode silicon waveguide. Radiative scattering at the
      crossing points acts like a periodic imaginary-permittivity perturbation that
      couples two supermodes, which results in imaginary (radiative) propagation
      constant splitting and gives rise to a low-loss, unidirectional breathing Bloch
      wave. This type of crossing array provides a robust implementation of a key
      component enabling dense photonic integration.

PMID- 24562141
TI  - Direct method to control surface plasmon polaritons on metal surfaces.
AB  - The manipulation of surface plasmon polaritons (SPPs) on metal surfaces is an
      important aspect in the design of ultra-compact integrated micro/nano optical
      systems. We present a direct method for the easy, yet accurate design of
      complicated groove patterns to control SPPs traveling on metal surfaces, using a
      surface electromagnetic wave holography method, based on the Huygens-Fresnel
      principle. SPPs are scattered by these deliberately and appropriately determined
      groove patterns and interfere with each other to form new paths with desire. Two
      devices are demonstrated, with predesignated functionalities fully implemented by
      the designed plasmonic holographic structures, according to the finite-difference
      time-domain simulations. The results strongly indicate that this direct method is
      effective, efficient, and user friendly in its application to control SPPs on
      metal surfaces. 

PMID- 24562142
TI  - Generation and erasure of femtosecond laser-induced periodic surface structures
      on nanoparticle-covered silicon by a single laser pulse.
AB  - We experimentally show that the generation and erasure of femtosecond laser
      induced periodic surface structures on nanoparticle-covered silicon inducted by
      irradiation with a single laser pulse (800 nm, 120 fs, linear polarization)
      depend on the pulse fluence. We propose that this is due to competition between
      periodic surface structuring originating from the interference of incident light
      with surface plasmon polaritons and surface smoothing associated with surface
      melting. Experimental results are supported by theoretical analysis of transient
      surface modifications based on combining the two-temperature model and the Drude
      model.

PMID- 24562143
TI  - Light sources generating self-focusing beams of variable focal length.
AB  - A class of partially coherent beams with a nonuniformly cosine-Gaussian (NUCG)
      correlated function is introduced. The evolution behavior of scalar beams
      produced by these families of sources in free space and isotropic random media
      are investigated. It is shown that such light fields with NUCG correlated
      function propagating in free space and turbulent atmosphere have self-focusing
      effects and laterally shifted intensity maxima. The new source employs cosine
      function for modeling of the source degree of coherence, which can adjust the
      self-focusing focal length, the shift of intensity center, and the intensity
      profile. 

PMID- 24562144
TI  - Tandem gratings spectrometer for spectroscopy broadband anastigmatic imaging.
AB  - A tandem gratings spectrometer with high imaging quality is designed. By applying
      the geometric analysis, the spectral broadband anastigmatic imaging conditions
      have been obtained. It offers an advanced design with low aberrations for the
      whole spectral range of the small-scale spectrometer both in the off-axis and
      coaxial telescope applications. A UV design exhibiting excellent optical
      performance is presented. The specifications of design have also been
      investigated. 

PMID- 24562145
TI  - Tunable optical code converter using XPM and linear-slope pulse streams generated
      by FBGs.
AB  - We propose for the first time (to the best of our knowledge) and demonstrate a
      tunable multiple optical code (OC) converter for flexible networks that allows
      dynamic code (bandwidth) allocation in a way similar to a tunable laser. With
      respect to other OC converters, this scheme can convert both specific and
      multiple OCs by changing only the amplifier gain. The proposed scheme uses cross
      phase modulation (XPM) and two linear-slope control pulse streams generated by
      fiber Bragg gratings (FBGs) in the C-band. The OC converter can be used to avoid
      collisions in optical packet switching networks, and we analyze the corresponding
      packet loss probability performance. 

PMID- 24562146
TI  - Nonlinear fiber amplifier with tunable transform limited pulse duration from a
      few 100 to sub-100-fs at watt-level powers.
AB  - We report a fiber amplifier system with an output transform limited pulse
      duration that is broadly tunable from 400 to 60 fs. We produce <100 fs pulses
      with >200 kW of peak power by compensating a significant amount of third-order
      dispersion. The spectral noise characteristics are also investigated to insure
      highly stable supercontinuum generation.

PMID- 24562147
TI  - Phase-sensitive amplification in silicon photonic crystal waveguides.
AB  - We experimentally demonstrate phase-sensitive amplification in a silicon photonic
      crystal waveguide based on pump-degenerate four-wave mixing. An 11 dB phase
      extinction ratio is obtained in a record compact 196 MUm nanophotonic device due
      to broadband slow light, in spite of the presence of two-photon absorption and
      free carriers. Numerical calculations show good agreement with the experimental
      results.

PMID- 24562148
TI  - Two-dimensional apodized silicon photonic phased arrays.
AB  - In this Letter, we demonstrate an 8*8 apodized silicon photonic phased array
      where the emission from each of 64 nanoantennas was tailored to exhibit Gaussian
      shaped intensity distributions in the near field so that the sidelobes of the
      generated far-field optical beam were suppressed compared to that of a uniform
      phased array. With the aid of the 72 thermo-optic phase tuners directly
      integrated within the phased array, we dynamically shaped the generated optical
      beam in the far field in a variety of ways. 

PMID- 24562149
TI  - Optical characterization of ultra-short Bragg grating on lithium niobate ridge
      waveguide.
AB  - In this Letter, we report a technique to etch giant aspect ratio nanostructures
      in lithium niobate. An 8 MUm long Bragg grating on a Ti:LiNbO3 ridge waveguide
      was fabricated by combining optical-grade dicing and focused ion beam milling.
      The reflectivity was evaluated using an optical coherence tomography system: it
      is measured to be 53% for the TM wave and 47% for the TE wave. We study by 2D
      FDTD the modeled behavior of the electromagnetic field when an angle exists
      between two consecutive sidewalls of the grating in order to understand the
      difference between ideal Bragg grating and experimental samples. These
      simulations allow us to optimize the parameters in order to increase the
      reflection of the grating up to 80%.

PMID- 24562150
TI  - Dark current suppression of MgZnO metal-semiconductor-metal solar-blind
      ultraviolet photodetector by asymmetric electrode structures.
AB  - The application of asymmetric Schottky barrier and electrode area in an MgZnO
      metal-semiconductor-metal (MSM) solar-blind ultraviolet photodetector has been
      investigated by a physical-based numerical model in which the electron mobility
      is obtained by an ensemble Monte Carlo simulation combined with first principle
      calculations using the density functional theory. Compared with the experimental
      data of symmetric and asymmetric MSM structures based on ZnO substrate, the
      validity of this model is verified. The asymmetric Schottky barrier and electrode
      area devices exhibit reductions of 20 times and 1.3 times on dark current,
      respectively, without apparent photocurrent scarification. The plots of photo-to
      dark current ratio (PDR) indicate that the asymmetric MgZnO MSM structure has
      better dark current characteristic than that of the symmetric one. 

PMID- 24562151
TI  - Efficiency improvement and droop behavior in nanospherical-lens lithographically
      patterned bottom and top photonic crystal InGaN/GaN light-emitting diodes.
AB  - Large-scale SiO2 nanodisk arrays fabricated by nanospherical-lens lithography are
      embedded in the n-GaN and p-GaN layer of an InGaN/GaN light-emitting diode (LED)
      to produce photonic crystal (PC) structures for efficiency improvement. Following
      the obvious reduction of view angle, the light output power of bottom, top, and
      double PC LEDs is enhanced by 74.5%, 60.1%, and 88.2% compared to that of a
      conventional LED at 350 mA current, respectively. Despite the enhanced external
      quantum efficiency due to improved crystalline quality and light extraction,
      these PC LEDs exhibit lower peak efficiency current density and more serious
      efficiency droop than conventional LEDs. Combined with the rate equation, the
      droop mechanisms of PC LEDs have also been investigated experimentally and by
      simulation.

PMID- 24562152
TI  - Ultrashort optical pulse characterization using WS2 monolayers.
AB  - We demonstrate the application of two-dimensional materials for ultrashort
      optical pulse characterization. Monolayer transition metal dichalcogenides, such
      as tungsten disulfide (WS2), possess extraordinarily large second-order nonlinear
      susceptibility, and due to their atomic thickness, have relaxed phase-matching
      requirements and, hence, an inherently wide bandwidth. Synthesized monolayer WS2
      triangular islands were used to characterize ultrashort optical pulses at the
      focal point of an objective lens through second-harmonic generation collinear
      frequency-resolved optical gating.

PMID- 24562153
TI  - Double-channel vector spatial light modulator for generation of arbitrary complex
      vector beams.
AB  - We propose an approach for implementation of an arbitrary vector beam based on a
      vector spatial light modulator (VSLM), which is simply composed by a phase-only
      spatial light modulator (SLM) and a composed half-wave plate with checkerboard
      structure. In combination with a four-phase encoding algorithm, the VSLM can
      transform a linear polarized Gaussian beam or a plane wave into a vector beam
      with both arbitrary spatial polarization and complex amplitude distributions in
      two dimensions. It is demonstrated that the VSLM can directly transform pure
      phase values into two orthogonal polarized complex values with high-diffraction
      efficiency. Compared with the existing methods for generation of vector beams
      with SLMs, our approach is on-axis and common-path with simple structure and only
      involves the zero-order diffraction. The proposed structure is also easier to
      make an integration and design portable device since it abstains from using
      optical elements such as special gratings, prisms, and reflectors. 

PMID- 24562154
TI  - Two-photon quantum interference in plasmonics: theory and applications.
AB  - We report perfect two-photon quantum interference with near-unity visibility in a
      resonant tunneling plasmonic structure in folded Kretschmann geometry. This is
      despite absorption-induced loss of unitarity in plasmonic systems. The effect is
      traced to perfect destructive interference between the squares of amplitude
      reflection and transmission coefficients. We further highlight yet another
      remarkable potential of coincidence measurements as a probe with better
      resolution as compared to standard spectroscopic techniques. The finer features
      show up in both angle resolved and frequency resolved studies. 

PMID- 24562155
TI  - Self-mixing sensing system based on uncooled vertical-cavity surface-emitting
      laser array: linking multichannel operation and enhanced performance.
AB  - We compare the performance of a self-mixing (SM) sensing system based on an
      uncooled monolithic array of 24*1 vertical-cavity surface-emitting lasers
      (VCSELs) in two modes of operation: single active channel and the concurrent
      multichannel operation. We find that the signal-to-noise ratio of individual SM
      sensors in a VCSEL array is markedly improved by multichannel operation, as a
      consequence of the increased operational temperature of the sensors. The
      performance improvement can be further increased by manufacturing VCSEL arrays
      with smaller pitch. This has the potential to produce an imaging system with high
      spatial and temporal resolutions that can be operated without temperature
      stabilization. 

PMID- 24562156
TI  - New bounds on the capacity of the nonlinear fiber-optic channel.
AB  - We revisit the problem of estimating the nonlinear channel capacity of fiber
      optic systems. By taking advantage of the fact that a large fraction of the
      nonlinear interference between different wavelength-division-multiplexed channels
      manifests itself as phase noise, and by accounting for the long temporal
      correlations of this noise, we show that the capacity is notably higher than what
      is currently assumed. This advantage translates into nearly doubling of the link
      distance for a fixed transmission rate. 

PMID- 24562157
TI  - Fourier spectrum method to determine dose-to-clear in a photoresist.
AB  - A Fourier spectrum method to determine the dose-to-clear in a photoresist is
      proposed. The frequency content of scanning electron microscope resist images is
      used to determine whether the resist has been dissolved. Using this method, the
      dose to clear the resist is calculated automatically instead of via visual
      inspection, a method in which operator influence can affect the result. 

PMID- 24562158
TI  - Stabilization of nonlocal solitons by boundary conditions.
AB  - We discovered that boundary conditions can stabilize nonlocal solitons with an
      oscillatory periodic response function. These solitons are the equivalent of
      quadratic solitons consisting of fundamental waves and oscillatory second
      harmonics, which are unstable unless subject to boundary confinement. 

PMID- 24562159
TI  - Ion current as a precise measure of the loading rate of a magneto-optical trap.
AB  - We have demonstrated that the ion current resulting from collisions between
      metastable krypton atoms in a magneto-optical trap can be used to precisely
      measure the trap loading rate. We measured both the ion current of the abundant
      isotope 83Kr (isotopic abundance=11%) and the single-atom counting rate of the
      rare isotope 85Kr (isotopic abundance~1*10(-11)), and found the two quantities to
      be proportional at a precision level of 0.9%. This work results in a significant
      improvement in using the magneto-optical trap as an analytical tool for noble-gas
      isotope ratio measurements, and will benefit both atomic physics studies and
      applications in the earth sciences.

PMID- 24562160
TI  - Multi-wavelength filters in silicon using superposition sidewall Bragg grating
      devices.
AB  - Multiple-filter stopbands, with the potential to be nonuniformly spaced in
      frequency, are realized in a single integrated Bragg grating device on silicon.
      By utilizing a superposition of sidewall relief grating functions, N individual
      filter responses can be fabricated with a device length N* shorter than the
      equivalent serial set of gratings. Arbitrary combinations of eight-basis filter
      responses were demonstrated as selected by an eight-bit pseudorandom number
      generator, showing the flexibility of the complex Bragg grating device design. 

PMID- 24562161
TI  - Spectroscopic, crystallographic and theoretical studies of lasalocid complex with
      ammonia and benzylamine.
AB  - A natural antibiotic--Lasalocid is able to form stable complexes with ammonia and
      organic amines. New complexes of lasalocid with benzylamine and ammonia were
      obtained in the crystal forms and studied using X-ray, FT-IR, (1)H NMR, (13)C NMR
      and DFT methods. These studies have shown that in both complexes the proton is
      transferred from the carboxylic group to the amine group with the formation of a
      pseudo-cyclic structure of lasalocid anion complexing the protonated amine or
      NH4(+) cation. The spectroscopic and DFT studies demonstrated that the structure
      of the complex formed between Lasalocid and benzylamine in the solid is also
      conserved in the solution and gas phase. In contrast, the structure of the
      complex formed between lasalocid and ammonium cation found in the solid state
      undergoes dissociation in chloroform solution accompanied with a change in the
      coordination form of the NH4(+) cation.

PMID- 24562162
TI  - Influence of Cs(I)-doping on the spectral, thermal, morphological and optical
      properties of bis(thiourea)zinc(II) chloride crystals.
AB  - Single crystals of alkali metal caesium(I) doped bis(thiourea)zinc(II) chloride
      are grown at room temperature by slow evaporation solution growth technique.
      Powder XRD studies reveal some interesting features in the XRD profiles with
      changes in intensity patterns in doped specimen due to stress development in the
      crystal. The incorporation of Cs(I) into the crystal lattice was confirmed by
      energy dispersive X-ray spectroscopy. Slight shifts in vibrational patterns of
      doped specimen indicate that the crystal undergoes considerable lattice stress as
      result of doping. SEM studies of pure and doped samples reveal the external
      morphology. Thermogravimetric and differential thermal studies reveal the purity
      of the material and the specimens are stable up to the melting point. The optical
      studies reveal that absorption is minimum in the visible region and doping
      influenced the diffuse reflectance spectrum. The band gap energies of the pure
      and doped specimens were estimated by the application of Kubelka-Munk algorithm. 

PMID- 24562163
TI  - Shear dynamics of nanoconfined ionic liquids.
AB  - We used molecular dynamics simulations to study the structure and shear dynamics
      of two ionic liquids (ILs) featuring the same cation 1-butyl-3-methyl-imidazolium
      or [BMIM], paired with bis(trifluoromethanesulphonyl)amide [NTF2] and
      tetrafluoroborate [BF4] anions, confined between two hydroxylated silica
      surfaces. The results demonstrate how the shape of IL molecules affects their
      layering structure at hydroxylated silica surfaces and how the layered structure
      of nanoconfined liquids determines their dynamical properties at the molecular
      level. When [BMIM][NTF2] is sheared, larger molecular fluctuations in the inner
      layers are required to stabilise the system, and the resulting dynamics is
      irregular. The alternating charged layers in [BMIM][BF4] allow the system to
      stabilise through smaller oscillations, and the layers appear to shear on top of
      each other in a laminar fashion. The simulated dynamics explains qualitatively
      the relative change in viscosity that the two ILs exhibit when confined, as has
      been observed in previous experiments. 

PMID- 24562173
TI  - Popular exclusionary diets for inflammatory bowel disease: the search for a
      dietary culprit.
AB  - The evolving understanding of the role of the microbiome and environmental
      factors in the pathogenesis of inflammatory bowel disease makes diet an
      interesting and potentially powerful tool in the treatment of disease. However,
      at this time, evidence is limited but anecdotal reports of success abound. There
      is a bewildering array of new diets being tried by patients in an attempt to
      control diseases. This review attempts to summarize the most common diets for the
      treating physician.

PMID- 24562174
TI  - Clinical utility of fecal biomarkers for the diagnosis and management of
      inflammatory bowel disease.
AB  - Diagnosis and monitoring of inflammatory bowel diseases rely on clinical,
      endoscopic, and radiologic parameters. Inflammatory biomarkers have been
      investigated as a surrogate marker for endoscopic diagnosis of inflammatory
      activity. Fecal inflammatory biomarkers such as calprotectin and lactoferrin are
      direct products of bowel inflammation and provide an accurate and noninvasive
      diagnostic and monitoring modality for Crohn's disease and ulcerative colitis.
      This report contains an overview of the currently existing literature pertaining
      to clinical implications of fecal biomarkers for diagnosis, monitoring, and
      prediction of outcomes of inflammatory bowel disease.

PMID- 24562164
TI  - Estimating the heritability of colorectal cancer.
AB  - A sizable fraction of colorectal cancer (CRC) is expected to be explained by
      heritable factors, with heritability estimates ranging from 12 to 35% twin and
      family studies. Genome-wide association studies (GWAS) have successfully
      identified a number of common single-nucleotide polymorphisms (SNPs) associated
      with CRC risk. Although it has been shown that these CRC susceptibility SNPs only
      explain a small proportion of the genetic risk, it is not clear how much of the
      heritability these SNPs explain and how much is left to be detected by other, yet
      to be identified, common SNPs. Therefore, we estimated the heritability of CRC
      under different scenarios using Genome-Wide Complex Trait Analysis in the
      Genetics and Epidemiology of Colorectal Cancer Consortium including 8025 cases
      and 10 814 controls. We estimated that the heritability explained by known common
      CRC SNPs identified in GWAS was 0.65% (95% CI:0.3-1%; P = 1.11 * 10-16), whereas
      the heritability explained by all common SNPs was at least 7.42% (95% CI: 4.71
      10.12%; P = 8.13 * 10(-8)), suggesting that many common variants associated with
      CRC risk remain to be detected. Comparing the heritability explained by the
      common variants with that from twin and family studies, a fraction of the
      heritability may be explained by other genetic variants, such as rare variants.
      In addition, our analysis showed that the gene * smoking interaction explained a
      significant proportion of the CRC variance (P = 1.26 * 10(-2)). In summary, our
      results suggest that known CRC SNPs only explain a small proportion of the
      heritability and more common SNPs have yet to be identified. 

PMID- 24562176
TI  - Environment and risk of Crohn's disease: comments on "the increasing weight of
      Crohn's disease subjects in clinical trials".

PMID- 24562177
TI  - Structural elucidation of an asparagine-linked oligosaccharide from the
      hyperthermophilic archaeon, Pyrococcus furiosus.
AB  - An oligosaccharide chain attached to the asparagine residue in a structurally
      defined peptide was produced by an in vitro oligosaccharide-transfer reaction,
      using membrane fractions that contained the oligosaccharyltransferase from the
      hyperthermophilic archaeon, Pyrococcus furiosus. The chemical structure of the N
      glycan was elucidated by sugar analysis, NMR spectroscopy, and MS spectrometry,
      which revealed the structure. The shorter glycan structures lacking one or two
      xylose residues were also transferred by the P. furiosus
      oligosaccharyltransferase. The archaeal N-glycans are known to exhibit a high
      degree of structural variation. The structure of the P. furiosus N-glycan is
      novel and unique. The present data will be useful for structural and functional
      studies of the P. furiosus oligosaccharyltransferase. 

PMID- 24562175
TI  - The effects of infliximab or adalimumab on vascular endothelial growth factor and
      angiopoietin 1 angiogenic factor levels in inflammatory bowel disease: serial
      observations in 37 patients.
AB  - BACKGROUND: Infliximab and adalimumab effectiveness might be related with changes
      in angiogenic factors. The aim of the study was to compare the concentrations of
      angiogenic proteins in patients with inflammatory bowel disease (IBD) and healthy
      controls and to analyze changes in the levels during infliximab and adalimumab
      treatment. METHODS: A prospective case-control study was conducted in 37 patients
      with IBD starting treatment with infliximab (16 with Crohn's disease and 6 with
      ulcerative colitis) or adalimumab (15 with Crohn's disease) and 40 control
      subjects. Four samples were taken from IBD patients, one before each of the first
      3 doses of infliximab/adalimumab and one at week 14. Serum levels of vascular
      endothelial growth factor (VEGF), placental growth factor, angiopoietin 1 (Ang1),
      angiopoietin 2, and Tie2 were measured using enzyme-linked immunosorbent assay.
      RESULTS: Patients with IBD had higher VEGF levels than control subjects (511.5 +/
      255.6 versus 395.5 +/- 256.4; P = 0.05). Patients who achieved remission at the
      third dose of anti-TNF-alpha had lower VEGF levels at baseline (453.5 +/- 250.7
      versus 667.5 +/- 153.9 pg/mL) and before the second (409.7 +/- 217 versus 681.3
      +/- 350.6 pg/mL) and third (400.5 +/- 222.8 versus 630.4 +/- 243.1 pg/mL) doses
      compared with those with no remission (P < 0.05). Ang1 levels decreased before
      each treatment dose in patients who achieved remission (P < 0.05). High baseline
      VEGF levels predicted for a poor response to anti-TNF-alpha therapy (area under
      the receiver operating characteristics curve = 0.8), whereas high Ang1 levels
      were associated with disease remission (area under the receiver operating
      characteristics curve = 0.7). Concentrations of angiogenic proteins did not
      correlate with clinical activity scores. CONCLUSIONS: Circulating VEGF and Ang1
      levels decrease after anti-TNF-alpha therapy and may predict response to
      treatment. Whether these changes are a direct effect of anti-TNF-alpha therapy or
      a sign of disease improvement remains to be elucidated.

PMID- 24562178
TI  - Microorganisms living on macroalgae: diversity, interactions, and
      biotechnological applications.
AB  - Marine microorganisms play key roles in every marine ecological process, hence
      the growing interest in studying their populations and functions. Microbial
      communities on algae remain underexplored, however, despite their huge
      biodiversity and the fact that they differ markedly from those living freely in
      seawater. The study of this microbiota and of its relationships with algal hosts
      should provide crucial information for ecological investigations on algae and
      aquatic ecosystems. Furthermore, because these microorganisms interact with algae
      in multiple, complex ways, they constitute an interesting source of novel
      bioactive compounds with biotechnological potential, such as dehalogenases,
      antimicrobials, and alga-specific polysaccharidases (e.g., agarases,
      carrageenases, and alginate lyases). Here, to demonstrate the huge potential of
      alga-associated organisms and their metabolites in developing future
      biotechnological applications, we first describe the immense diversity and
      density of these microbial biofilms. We further describe their complex
      interactions with algae, leading to the production of specific bioactive
      compounds and hydrolytic enzymes of biotechnological interest. We end with a
      glance at their potential use in medical and industrial applications.

PMID- 24562179
TI  - The gamma-butyrolactone receptors BulR1 and BulR2 of Streptomyces tsukubaensis:
      tacrolimus (FK506) and butyrolactone synthetases production control.
AB  - Streptomyces tsukubaensis is a well-established industrial tacrolimus producer
      strain, but its molecular genetics is very poorly known. This information
      shortage prevents the development of tailored mutants in the regulatory pathways.
      A region (named bul) contains several genes involved in the synthesis and control
      of the gamma-butyrolactone autoregulator molecules. This region contains ten
      genes (bulA, bulZ, bulY, bulR2, bulS2, bulR1, bulW, bluB, bulS1, bulC) including
      two gamma-butyrolactone receptor homologues (bulR1, bulR2), two putative gamma
      butyrolactone synthetase homologues (bulS1, bulS2) and two SARP regulatory genes
      (bulY, bulZ). Analysis of the autoregulatory element (ARE)-like sequences by
      electrophoretic mobility shift assays and footprinting using the purified BulR1
      and BulR2 recombinant proteins revealed six ARE regulatory sequences distributed
      along the bul cluster. These sequences showed specific binding of both BulR1 (the
      gamma-butyrolactone receptor) and BulR2, a possible pseudo gamma-butyrolactone
      receptor. The protected region in all cases covered a 28-nt sequence with a
      palindromic structure. Optimal docking area analysis of BulR1 proved that this
      protein can be presented as either monomer or dimer but not oligomers and that it
      binds to the conserved ARE sequence in both strands. The effect on tacrolimus
      production was analysed by deletion of the bulR1 gene, which resulted in a strong
      decrease of tacrolimus production. Meanwhile, the DeltabulR2 mutation did not
      affect the biosynthesis of this immunosuppressant. 

PMID- 24562180
TI  - Acute toxicity of multi-walled carbon nanotubes, sodium pentachlorophenate, and
      their complex on earthworm Eisenia fetida.
AB  - Laboratory experiments were undertaken to relate biomarker responses to the
      toxicities of multi-walled carbon nanotubes (MWCNTs) and sodium
      pentachlorophenate (PCP-Na), both individually and combined. The acute toxicities
      of MWCNTs and PCP-Na on earthworm Eisenia fetida were studied through different
      exposure methods (filter paper contact test, immersion contact test, and
      artificial soil contact test). Enzyme activity and malondialdehyde (MDA) content
      in the earthworm E. fetida exposed to MWCNTs and PCP-Na in filter paper contact
      test, both individually and under combined exposure, were determined. After
      exposure, PCP-Na induced observable acute toxicity while the MWCNTs induced
      slight toxicity. Interestingly the earthworms exposed to the mixture of MWCNTs
      and PCP-Na demonstrated different expression of enzymatic biomarkers from those
      exposed to MWCNTs or PCP-Na alone. Our results indicated that the toxicity of PCP
      Na on E. fetida may be alleviated by the appearance of MWCNTs for all exposure
      methods except for immersion contact test. 

PMID- 24562181
TI  - Ethoprophos fate on soil-water interface and effects on non-target terrestrial
      and aquatic biota under Mediterranean crop-based scenarios.
AB  - The present study aimed to assess the environmental fate of the insecticide and
      nematicide ethoprophos in the soil-water interface following the pesticide
      application in simulated maize and potato crops under Mediterranean agricultural
      conditions, particularly of irrigation. Focus was given to the soil-water
      transfer pathways (leaching and runoff), to the pesticide transport in soil
      between pesticide application (crop row) and non-application areas (between crop
      rows), as well as to toxic effects of the various matrices on terrestrial and
      aquatic biota. A semi-field methodology mimicking a "worst-case" ethoprophos
      application (twice the recommended dosage for maize and potato crops: 100%
      concentration v/v) in agricultural field situations was used, in order to mimic a
      possible misuse by the farmer under realistic conditions. A rainfall was
      simulated under a slope of 20 degrees  for both crop-based scenarios. Soil and
      water samples were collected for the analysis of pesticide residues. Ecotoxicity
      of soil and aquatic samples was assessed by performing lethal and sublethal
      bioassays with organisms from different trophic levels: the collembolan Folsomia
      candida, the earthworm Eisenia andrei and the cladoceran Daphnia magna. Although
      the majority of ethoprophos sorbed to the soil application area, pesticide
      concentrations were detected in all water matrices illustrating pesticide
      transfer pathways of water contamination between environmental compartments.
      Leaching to groundwater proved to be an important transfer pathway of ethoprophos
      under both crop-based scenarios, as it resulted in high pesticide concentration
      in leachates from Maize (130ugL(-1)) and Potato (630ugL(-1)) crop scenarios,
      respectively. Ethoprophos application at the Potato crop scenario caused more
      toxic effects on terrestrial and aquatic biota than at the Maize scenario at the
      recommended dosage and lower concentrations. In both crop-based scenarios,
      ethoprophos moved with the irrigation water flow to the soil between the crop
      rows where no pesticide was applied, causing toxic effects on terrestrial
      organisms. The two simulated agricultural crop-based scenarios had the merit to
      illustrate the importance of transfer pathways of pesticides from soil to
      groundwater through leaching and from crop rows to the surrounding soil areas in
      a soil-water interface environment, which is representative for irrigated
      agricultural crops under Mediterranean conditions. 

PMID- 24562183
TI  - Fabry disease deposition mimicking a cardiac tumour and precipitating heart
      block.

PMID- 24562182
TI  - Glyphosate, hard water and nephrotoxic metals: are they the culprits behind the
      epidemic of chronic kidney disease of unknown etiology in Sri Lanka?
AB  - The current chronic kidney disease epidemic, the major health issue in the rice
      paddy farming areas in Sri Lanka has been the subject of many scientific and
      political debates over the last decade. Although there is no agreement among
      scientists about the etiology of the disease, a majority of them has concluded
      that this is a toxic nephropathy. None of the hypotheses put forward so far could
      explain coherently the totality of clinical, biochemical, histopathological
      findings, and the unique geographical distribution of the disease and its
      appearance in the mid-1990s. A strong association between the consumption of hard
      water and the occurrence of this special kidney disease has been observed, but
      the relationship has not been explained consistently. Here, we have hypothesized
      the association of using glyphosate, the most widely used herbicide in the
      disease endemic area and its unique metal chelating properties. The possible role
      played by glyphosate-metal complexes in this epidemic has not been given any
      serious consideration by investigators for the last two decades. Furthermore, it
      may explain similar kidney disease epidemics observed in Andra Pradesh (India)
      and Central America. Although glyphosate alone does not cause an epidemic of
      chronic kidney disease, it seems to have acquired the ability to destroy the
      renal tissues of thousands of farmers when it forms complexes with a localized
      geo environmental factor (hardness) and nephrotoxic metals. 

PMID- 24562184
TI  - Isolated left ventricular arrhythmogenic dysplasia.

PMID- 24562185
TI  - Method for obtaining primary ovarian cancer cells from solid specimens.
AB  - Reliable tools for investigating ovarian cancer initiation and progression are
      urgently needed. While the use of ovarian cancer cell lines remains a valuable
      tool for understanding ovarian cancer, their use has many limitations. These
      include the lack of heterogeneity and the plethora of genetic alterations
      associated with extended in vitro passaging. Here we describe a method that
      allows for rapid establishment of primary ovarian cancer cells form solid
      clinical specimens collected at the time of surgery. The method consists of
      subjecting clinical specimens to enzymatic digestion for 30 min. The isolated
      cell suspension is allowed to grow and can be used for downstream application
      including drug screening. The advantage of primary ovarian cancer cell lines over
      established ovarian cancer cell lines is that they are representative of the
      original specific clinical specimens they are derived from and can be derived
      from different sites whether primary or metastatic ovarian cancer.

PMID- 24562186
TI  - Outer Co(II) ions in Co-ZIF-67 reversibly adsorb oxygen from both gas phase and
      liquid water.
AB  - Outer Co(II) species in Co-ZIF-67 coordinate molecular oxygen both from the gas
      phase and liquid water, through an adsorption process (presumably yielding in
      both cases surface superoxo species), respectively weak and reversible (gas
      phase), and strong and irreversible (liquid); in the latter case desorption is
      however brought about by illumination with solar light comprising the UV
      component.

PMID- 24562187
TI  - Direct measurement of transcription factor dissociation excludes a simple
      operator occupancy model for gene regulation.
AB  - Transcription factors mediate gene regulation by site-specific binding to
      chromosomal operators. It is commonly assumed that the level of repression is
      determined solely by the equilibrium binding of a repressor to its operator.
      However, this assumption has not been possible to test in living cells. Here we
      have developed a single-molecule chase assay to measure how long an individual
      transcription factor molecule remains bound at a specific chromosomal operator
      site. We find that the lac repressor dimer stays bound on average 5 min at the
      native lac operator in Escherichia coli and that a stronger operator results in a
      slower dissociation rate but a similar association rate. Our findings do not
      support the simple equilibrium model. The discrepancy with this model can, for
      example, be accounted for by considering that transcription initiation drives the
      system out of equilibrium. Such effects need to be considered when predicting
      gene activity from transcription factor binding strengths. 

PMID- 24562191
TI  - Optical Mobius strips and twisted ribbon cloaks.
AB  - Optical Mobius strips that surround points of circular polarization, C points, in
      a generic three-dimensional optical field are cloaked by lines of twisted ribbons
      attached to the C points. When cloaking occurs, the observable signed twist index
      that counts the number of half-twists (one or three), and also measures the
      handedness (right or left), of a generic Mobius strip is determined by the
      twisted ribbon cloaks. Although some cloaks can be detached, they can never all
      be removed. 

PMID- 24562192
TI  - Hybrid coding method of multiple orbital angular momentum states based on the
      inherent orthogonality.
AB  - We put forward a hybrid coding method of multiple orbital angular momentum (OAM)
      states based on the inherent orthogonality. Theoretical analysis shows this new
      coding method can tremendously improve the coding efficiency compared to the
      conventional way, and the OAM mode can be extended to all the transverse
      orthographic modes such as Bessel beams or Laguerre-Gauss modes. We also present
      a typical scheme to achieve the encoding of hybrid OAM states based on a
      concentric ring resonator array. We further suggest a digital device and a phase
      hologram pattern to decode the hybrid OAM states. 

PMID- 24562190
TI  - High throughput electron transfer from carbon dots to chloroplast: a rationale of
      enhanced photosynthesis.
AB  - A biocompatible amine functionalized fluorescent carbon dots were developed and
      isolated for gram scale applications. Such carbogenic quantum dots can strongly
      conjugate over the surface of the chloroplast and due to that strong interaction
      the former can easily transfer electrons towards the latter by assistance of
      absorbed light or photons. An exceptionally high electron transfer from carbon
      dots to the chloroplast can directly effect the whole chain electron transfer
      pathway in a light reaction of photosynthesis, where electron carriers play an
      important role in modulating the system. As a result, carbon dots can promote
      photosynthesis by modulating the electron transfer process as they are capable of
      fastening the conversion of light energy to the electrical energy and finally to
      the chemical energy as assimilatory power (ATP and NADPH). 

PMID- 24562193
TI  - Experimental characterization of phase tuning using fine wavelength offsets in a
      tunable complex-coefficient optical tapped-delay-line.
AB  - We use fine-detuning of pump wavelengths to adjust the tap phases in a complex
      coefficient optical tapped-delay-line that utilizes conversion/dispersion-based
      delays and nonlinear wave mixing. Full 2pi phase tuning is demonstrated by
      detuning the frequency of laser pumps by <20  GHz, which shows close agreement
      with theory.

PMID- 24562194
TI  - 100 kHz thousand-frame burst-mode planar imaging in turbulent flames.
AB  - High-repetition-rate, burst-mode lasers can achieve higher energies per pulse
      compared with continuously pulsed systems, but the relatively few number of laser
      pulses in each burst has limited the temporal dynamic range of measurements in
      unsteady flames. A fivefold increase in the range of timescales that can be
      resolved by burst-mode laser-based imaging systems is reported in this work by
      extending a hybrid diode- and flashlamp-pumped Nd:YAG-based amplifier system to
      nearly 1000 pulses at 100 kHz during a 10 ms burst. This enables an unprecedented
      burst-mode temporal dynamic range to capture turbulent fluctuations from 0.1 to
      50 kHz in flames of practical interest. High pulse intensity enables efficient
      conversion to the ultraviolet for planar laser-induced fluorescence imaging of
      nascent formaldehyde and other potential flame radicals.

PMID- 24562195
TI  - Broadband parametric wavelength conversion at 1 MUm with large mode area fibers.
AB  - Fiber-optic parametric wavelength conversion (PWC) below the zero-dispersion
      wavelength of silica is typically constrained by the requirement of a small,
      tightly confined mode with anomalous dispersion to achieve phase matching. This
      limits the ability to power scale PWC at arbitrary wavelengths. However, the
      constraint is lifted for higher-order modes. We demonstrate PWC in the 1 MUm band
      via degenerate four-wave mixing pumped in a large effective area (>600  MUm2)
      LP(0,7) mode of a double-clad fiber. We obtain up to 25% conversion in to the
      Stokes line with 0.5 ns pump pulses, corresponding to ~20  kW peak power at the
      converted wavelength.

PMID- 24562196
TI  - High spectral power femtosecond supercontinuum source by use of microlens array.
AB  - Generation of a high spectral power supercontinuum (SC) is reported from
      controlled multifilamentation of femtosecond pulses in fused silica. The use of a
      microlens array allows the manipulation of the filamentation pattern under very
      high-incident laser pulse energy without sample damage and, consequently,
      compared with using a single focusing lens, higher power of SC generation with a
      similar spectral broadening can be obtained. Moreover, the role of the interplay
      between diffraction pattern and proximity to the focus of the microlens array in
      SC generation is discussed. 

PMID- 24562188
TI  - Pathogens and host immunity in the ancient human oral cavity.
AB  - Calcified dental plaque (dental calculus) preserves for millennia and entraps
      biomolecules from all domains of life and viruses. We report the first, to our
      knowledge, high-resolution taxonomic and protein functional characterization of
      the ancient oral microbiome and demonstrate that the oral cavity has long served
      as a reservoir for bacteria implicated in both local and systemic disease. We
      characterize (i) the ancient oral microbiome in a diseased state, (ii) 40
      opportunistic pathogens, (iii) ancient human-associated putative antibiotic
      resistance genes, (iv) a genome reconstruction of the periodontal pathogen
      Tannerella forsythia, (v) 239 bacterial and 43 human proteins, allowing
      confirmation of a long-term association between host immune factors, 'red
      complex' pathogens and periodontal disease, and (vi) DNA sequences matching
      dietary sources. Directly datable and nearly ubiquitous, dental calculus permits
      the simultaneous investigation of pathogen activity, host immunity and diet,
      thereby extending direct investigation of common diseases into the human
      evolutionary past. 

PMID- 24562197
TI  - Fast and efficient silicon thermo-optic switching based on reverse breakdown of
      pn junction.
AB  - We propose and demonstrate a fast and efficient silicon thermo-optic switch based
      on reverse breakdown of the pn junction. Benefiting from the direct heating of
      silicon waveguide by embedding the pn junction into the waveguide center, fast
      switching with on/off time of 330 and 450 ns and efficient thermal tuning of 0.12
      nm/mW for a 20 MUm radius microring resonator are achieved, indicating a high
      figure of merit of only 8.8  mW.MUs. The results here show great potential for
      application in the future optical interconnects.

PMID- 24562198
TI  - Multiple-beam output of a surface-emitted terahertz-wave parametric oscillator by
      using a slab MgO:LiNbO3 crystal.
AB  - A MgO:LiNbO3 slab configuration for the surface-emitted terahertz-wave parametric
      oscillator (TPO) is presented. The pump and the oscillating Stokes beams were
      totally reflected at the slab surface and propagated zigzaggedly in the slab
      MgO:LiNbO3 crystal. Up to five terahertz beams were emitted perpendicularly to
      the surface of the crystal. The total output energy of the five THz-wave beams
      was 3.56 times as large as that obtained from the conventional surface-emitted
      TPO at the same experimental conditions. The intensity distributions of the THz
      wave beams were measured, and they were unsymmetrical in the horizontal direction
      while symmetrical in the vertical direction.

PMID- 24562199
TI  - On-chip multiplexing conversion between wavelength division multiplexing
      polarization division multiplexing and wavelength division multiplexing-mode
      division multiplexing.
AB  - A compact silicon-on-insulator device used for conversions between polarization
      division multiplexing (PDM) and mode division multiplexing (MDM) signals is
      proposed and experimentally demonstrated by utilizing a structure combining the
      improved two-dimensional grating coupler and two-mode multiplexer. The detailed
      design of the proposed device is presented and the results show the extinction
      ratio of 16 and 20 dB for X- and Y-pol input, respectively. The processing of 40 
      Gb/s signal is achieved within the C-band with good performance. The proposed
      converter is capable of handling multiple wavelengths in wavelength division
      multiplexing (WDM) networks, enabling the conversions between WDM-PDM and WDM
      MDM, which is promising to further increase the throughput at the network
      interface.

PMID- 24562200
TI  - Smart design to resolve spectral overlapping of phosphor-in-glass for high
      powered remote-type white light-emitting devices.
AB  - The white light-emitting diode (WLED) is a state-of-the-art solid state
      technology, which has replaced conventional lighting systems due to its reduced
      energy consumption, its reliability, and long life. However, the WLED presents
      acute challenges in device engineering, due to its lack of color purity,
      efficacy, and thermal stability of the lighting devices. The prime cause for
      inadequacies in color purity and luminous efficiency is the spectral overlapping
      of red components with yellow/green emissions when generating white light by
      pumping a blue InGaN chip with yellow YAG:Ce3+ phosphor, where red phosphor is
      included, to compensate for deficiencies in the red region. An innovative
      strategy was formulated to resolve this spectral overlapping by alternatively
      arranging phosphor-in-glass (PiG) through cutting and reassembling the commercial
      red CaAlSiN3:Eu2+ and green Lu3Al5O12:Ce3+ PiG. PiGs were fabricated using glass
      frits with a low softening temperature of 600 degrees C, which exhibited
      excellent thermal stability and high transparency, improving life time even at an
      operating temperature of 200 degrees C. This strategy overcomes the spectral
      overlapping issue more efficiently than the randomly mixed and patented stacking
      design of multiple phosphors for a remote-type WLED. The protocol for the current
      design of PiG possesses excellent thermal and chemical stability with high
      luminous efficiency and color purity is an attempt to make smarter solid state
      lighting for high-powered remote-type white light-emitting devices.

PMID- 24562201
TI  - Stimulated Raman spectroscopy with 0pi pulses.
AB  - We developed a new variant of stimulated Raman spectroscopy with shaped short
      pulses, applicable to multiscattering media. The technique is based on the
      spectral modulation of the laser pulse due to the Raman scattering and may have a
      broad range of applications from spectroscopy and pathogen detection to
      microscopy. 

PMID- 24562202
TI  - Experimental generation of cosine-Gaussian-correlated Schell-model beams with
      rectangular symmetry.
AB  - Cosine-Gaussian-correlated Schell-model sources whose degree of coherence (DOC)
      is of circular symmetry have been introduced just recently [Opt. Lett. 38, 2578
      (2013)]. In this Letter, we propose a model for a source whose DOC is the
      superposition of two 1D cosine-Gaussian-correlated Schell-model sources, i.e.,
      possesses rectangular symmetry. The novel model sources and beams they generate
      are termed rectangular cosine-Gaussian Schell-model (RCGSM). The RCGSM beam
      exhibits unique features on propagation, e.g., its intensity in the far field (or
      in the focal plane) displays a four-beamlet array profile, being qualitatively
      different from the ring-shaped profile of the CGSM beam whose DOC is of circular
      symmetry. Furthermore, we have carried out experimental generation of the
      proposed beam and measured its focusing properties. Our experimental results are
      consistent with the theoretical predictions.

PMID- 24562203
TI  - High-numerical-aperture microlensed tip on an air-clad optical fiber.
AB  - We show that a hemispherically shaped tip on an air-clad optical fiber
      simultaneously works as a high-numerical-aperture lens and efficiently collects
      photons from an emitter placed near the beam waist into the fundamental guided
      mode. Numerical simulations show that the coupling efficiency reaches about 25%.
      We have constructed a confocal microscope with such a lensed fiber. The
      measurements are in good agreement with the numerical simulation. The monolithic
      structure with a high-photon-collection efficiency will provide a flexible
      substitute for a conventional lens system in various experiments such as single
      atom trapping with a tightly focused optical trap. 

PMID- 24562204
TI  - Terahertz wave generation from thin metal films excited by asymmetrical optical
      fields.
AB  - We experimentally demonstrated terahertz (THz) wave emission from thin metal
      (gold) films excited by asymmetrical optical fields synthesized using an in-line
      phase compensator. By driving the electrons in thin metal films asymmetrically,
      THz wave emission is observed at normal incidence of two-color pump beams.
      Coherent control of THz wave emission from metal films suggests that a mechanism
      similar to that of the air-plasma THz source excited by two-color laser fields
      can be used to describe the generation processes. 

PMID- 24562205
TI  - Simple design of slanted grating with simplified modal method.
AB  - A simplified modal method (SMM) is presented that offers a clear physical image
      for subwavelength slanted grating. The diffraction characteristic of the slanted
      grating under Littrow configuration is revealed by the SMM as an equivalent
      rectangular grating, which is in good agreement with rigorous coupled-wave
      analysis. Based on the equivalence, we obtained an effective analytic solution
      for simplifying the design and optimization of a slanted grating. It offers a new
      approach for design of the slanted grating, e.g., a 1*2 beam splitter can be
      easily designed. This method should be helpful for designing various new slanted
      grating devices. 

PMID- 24562206
TI  - Low-noise and broadband optical frequency comb generation based on an
      optoelectronic oscillator.
AB  - A novel scheme to generate broadband high-repetition-rate optical frequency combs
      and low phase noise microwave signals simultaneously is proposed and
      experimentally demonstrated. By incorporating an optical frequency comb generator
      in an optoelectronic oscillator loop, more than 200 lines are generated for a 25
      GHz optical frequency comb, and the single-sideband phase noise is as low as -122
      dBc/Hz at 10 kHz offset for the 25 GHz microwave signal. 10 and 20 GHz optical
      frequency combs and microwave signals are also generated. Unlike the microwave
      frequency synthesizer, the phase noise of the microwave signals generated by this
      new scheme is frequency independent.

PMID- 24562207
TI  - Isoplanatic angle in finite distance: theory analysis on measurement feasibility.
AB  - Previous studies have shown that the isoplanatic angle (theta0) can be measured
      by using plane-wave scintillation. The problem of measuring the isoplanatic angle
      in a finite distance using spherical-wave scintillation is considered in this
      Letter. Based on theoretical analysis and numerical evaluation, we found that by
      selecting suitable aperture size and aperture separations, the isoplanatic angle
      can be estimated through spherical-wave scintillation and covariance of
      irradiance in three received apertures using a point source. The error of theta0
      measured by this method is less than 6% in typical turbulence models.

PMID- 24562208
TI  - High extinction ratio and low transmission loss thin-film terahertz polarizer
      with a tunable bilayer metal wire-grid structure.
AB  - A thin-film terahertz polarizer is proposed and realized via a tunable bilayer
      metal wire-grid structure to achieve high extinction ratios and good
      transmission. The polarizer is fabricated on top of a thin silica layer by
      standard micro-fabrication techniques to eliminate the multireflection effects.
      The tunable alignment of the bilayer aluminum-wire grid structure enables
      tailoring of the extinction ratio and transmission characteristics. Using
      terahertz time-domain spectroscopy (THz-TDS), a fabricated polarizer is
      characterized, with extinction ratios greater than 50 dB and transmission losses
      below 1 dB reported in the 0.2-1.1 THz frequency range. These characteristics can
      be improved by further tuning the polarizer parameters such as the pitch, metal
      film thickness, and lateral displacement.

PMID- 24562209
TI  - Silicon-based all-optical multi microring network-on-chip.
AB  - An optical multi microring network-on-chip (MMR NoC) is proposed and evaluated
      through numerical simulations. The network architecture consists of a central
      resonating microring with local microrings connected to the input/output ports. A
      mathematical model based on the transfer matrix method is used to assess the MMR
      NoC performance and to analyze the fabrication tolerances. Results show that the
      proposed architecture exhibits a limited coherent crosstalk with a bandwidth
      suitable for 10  Gb/s signals, and it is robust to coupling ratio variations and
      ring radii fabrication inaccuracies.

PMID- 24562210
TI  - Design and demonstration of a new kind of aperture for getting expected
      diffraction patterns.
AB  - In the regime of Fresnel diffraction, a novel algorithm is proposed for aperture
      design for getting expected diffraction patterns. Experiments have verified the
      feasibility of this method. It may be used in beam transition, optics
      communication, information encryption, and other related fields. 

PMID- 24562211
TI  - Direct formation of InN-codoped p-ZnO/n-GaN heterojunction diode by solgel spin
      coating scheme.
AB  - In this work p-ZnO/n-GaN heterojunction diodes were directly formed on the Si
      substrate by a combination of cost-effective solgel spin-coating and thermal
      annealing treatment. Spin-coated n-ZnO films on InN/GaN/Si wafers were converted
      to p-type polarity after thermal treatment of proper annealing durations. X-ray
      diffraction (XRD) analysis reveals that InN-codoped ZnO films have grown as the
      standard hexagonal wurtzite structure with a preferential orientation in the
      (002) direction. The intensity of the (002) peak decreases for a further extended
      annealing duration, indicating the greater incorporation of dopants, also
      confirmed by x-ray photoelectron spectroscopy and low-temperature
      photoluminescence. Hall and resistivity measurements validate that our p-type ZnO
      film has a high carrier concentration of 3.73*1017 cm-3, a high mobility of 210
      cm2/Vs, and a low resistivity of 0.079 Omegacm. As a result, the proposed p-ZnO/n
      GaN heterojunction diode displays a well-behaving current rectification of a
      typical p-n junction, and the measured current versus voltage (I-V)
      characteristic is hence well described by the modified Shockley equation. The
      research on the fabrication of p-ZnO/n-GaN heterojunctions shown here generates
      useful advances in the production of cost-effective ZnO-based optoelectronic
      devices.

PMID- 24562212
TI  - Birefringence measurement in the terahertz range based on double Fourier
      analysis.
AB  - A method for obtaining the average refractive indexes of a birefringent material
      in the terahertz region in a single measurement with a standard terahertz time
      domain spectrometer is presented. The method is based on processing the frequency
      domain interference between terahertz pulses and echoes through the Fourier
      transform of the terahertz spectrum. The technique also allows the determination
      of the optical axis orientation of the material by making two measurements with
      different angles of the sample optical axis. 

PMID- 24562213
TI  - Zero difference algorithm for phase shift extraction in blind phase-shifting
      holography.
AB  - A simple noniterative algorithm for retrieval of the unknown phase shifts in
      phase-shifting holography is proposed. In this algorithm, the phase shift value
      between two phase-shifting holograms can be calculated through a simple
      analytical formula that is derived according to the fact that there exist some
      points whose intensity difference between two phase-shifting holograms is equal
      to zero. Both the simulated and experimental results demonstrated the feasibility
      of this so-called zero difference algorithm over a wide range of phase shifts. 

PMID- 24562214
TI  - Absorption enhancement of single silicon nanowire by tailoring rear metallic film
      for photovoltaic applications.
AB  - In this work, single-nanowire solar cells (SCs) in lying configuration with a
      tunable rear metallic film are presented. Compared to the standalone silicon
      nanowire (SiNW), a significant/broadband enhancement in the overall optical
      absorption of the SiNW with rear metallic nanoconfiguration was observed. The
      optimized fraction, corresponding to the maximal ultimate photocurrent, of the
      SiNW surrounded by metallic film was achieved by properly engineering the SiNW
      radius and metallic film thickness. The considered configuration can be
      effectively extended to the alternative configuration with a SiNW partially
      embedded in a metallic substrate, where the ultimate photocurrent density of the
      100 nm radius SiNW can be improved by 75.50% relative to that of the freestanding
      SiNW. Our simulations verify that it is a promising route for developing highly
      efficient single nanowire SCs.

PMID- 24562215
TI  - Accuracy of the capillary approximation for gas-filled kagome-style photonic
      crystal fibers.
AB  - Precise knowledge of the group velocity dispersion in gas-filled hollow-core
      photonic crystal fiber is essential for accurate modeling of ultrafast nonlinear
      dynamics. Here we study the validity of the capillary approximation commonly used
      to calculate the modal refractive index in kagome-style photonic crystal fibers.
      For area-preserving core radius a(AP) and core wall thickness t, measurements and
      finite element simulations show that the approximation has an error greater than
      15% for wavelengths longer than 0.56?(a(AP)t), independently of the gas-filling
      pressure. By introducing an empirical wavelength-dependent core radius, the range
      of validity of the capillary approximation is extended out to a wavelength of at
      least 0.98?(a(AP)t).

PMID- 24562217
TI  - Closed-form solution of the steady-state photon diffusion equation in the
      presence of absorbing inclusions.
AB  - We have developed a theoretical model for photon migration through scattering
      media in the presence of an absorbing inhomogeneity. A closed-form solution for
      the average diffuse intensity has been obtained through an iterative
      approximation scheme of the steady-state diffusion equation. The model describes
      absorbing defects in a wide range of values. Comparisons with the results of
      Monte Carlo simulations show that the error of the model is lower than 3% for
      size inclusion lower than 4 mm and absorption contrast up to the threshold value
      of the "black defect." The proposed model provides a tractable mathematical basis
      for diffuse optical and photoacoustic tomographic reconstruction techniques.

PMID- 24562218
TI  - Laser differential confocal paraboloidal vertex radius measurement.
AB  - This Letter proposes a laser differential confocal paraboloidal vertex radius
      measurement (DCPRM) method for the high-accuracy measurement of the paraboloidal
      vertex radius of curvature. DCPRM constructs an autocollimation vertex radius
      measurement light path for the paraboloid by placing a reflector in the incidence
      light path. This technique is based on the principle that a paraboloid can aim a
      parallel beam at its focus without aberration and uses differential confocal
      positioning technology to identify the paraboloid focus and vertex accurately.
      Measurement of the precise distance between these two positions is achieved to
      determine the paraboloid vertex radius. Preliminary experimental results indicate
      that DCPRM has a relative expanded uncertainty of less than 0.001%. 

PMID- 24562219
TI  - Demonstration of flat-top focusing under radial polarization illumination.
AB  - We experimentally demonstrate the generation of a flat-top intensity distribution
      using a radially polarized vector beam. Our approach uses higher numerical
      aperture focusing than what has been previously reported for a single, fixed,
      vector beam. In addition, the flat-top focus generated in our scheme exhibits a
      polarization gradient along the radial coordinate in the focal volume, with an on
      axis longitudinal field component that persists over 2lambda, which is a stark
      difference from conventional flat-top fields, which exhibit intensity profiles
      that are uniformly polarized. Our experimental results are found to be in good
      agreement with the theoretical prediction. 

PMID- 24562221
TI  - Excited state Faraday anomalous dispersion optical filters based on indirect
      laser pumping.
AB  - The direct pump method now used in excited state Faraday anomalous dispersion
      optical filters (ES-FADOFs) requires that the transition between the target and
      the ground state is an electric dipole allowed transition and that a laser that
      operates at the exact pump wavelength is available. This is not always satisfied
      in practice. An indirect laser pump method for ES-FADOF is proposed and
      experimentally realized. Compared with the commonly used direct pump method, this
      indirect pump method can reach the same performance using lasers at very
      different wavelengths. This method can greatly extend the wavelength range of
      FADOF and provide a novel scheme for ES-FADOF design. 

PMID- 24562222
TI  - Directional infrared emission resulting from cascade population inversion and
      four-wave mixing in Rb vapor.
AB  - Directional infrared emission at 1.37 and 5.23 MUm is generated in Rb vapors that
      are stepwise excited by low-power cw resonant light. The radiation at 5.23 MUm
      originating from amplified spontaneous emission on the 5D(5/2)->6P(3/2)
      transition and wave mixing consists of forward- and backward-directed components
      with distinctive spectral and spatial properties. Diffraction-limited light at
      1.37 MUm generated in the copropagating direction only is a product of parametric
      wave mixing around the 5P(3/2)->5D(5/2)->6P(3/2)->6S(1/2)->5P(3/2) transition
      loop. This highly nondegenerate mixing process involves one externally applied
      and two internally generated optical fields. Similarities between wave mixing
      generated blue and 1.37 MUm light are demonstrated.

PMID- 24562220
TI  - Visualizing ultrasonically induced shear wave propagation using phase-sensitive
      optical coherence tomography for dynamic elastography.
AB  - We report on the use of phase-sensitive optical coherence tomography (PhS-OCT) to
      detect and track temporal and spatial shear wave propagation within tissue,
      induced by ultrasound radiation force. Kilohertz-range shear waves are remotely
      generated in samples using focused ultrasound emission and their propagation is
      tracked using PhS-OCT. Cross-sectional maps of the local shear modulus are
      reconstructed from local estimates of shear wave speed in tissue-mimicking
      phantoms. We demonstrate the feasibility of combining ultrasound radiation force
      and PhS-OCT to perform high-resolution mapping of the shear modulus. 

PMID- 24562223
TI  - Enhancing optical field intensities in Gaussian-profile fiber Bragg gratings.
AB  - Gaussian profile fiber Bragg gratings exhibit narrow-bandwidth transmission peaks
      with significant group delay at the edge of their photonic bandgap. We
      demonstrate group delays ranging from 0.2 to 5.6 ns from a 1.2 cm structure.
      Simulations suggest such a device would be capable of enhancing the field
      intensity of incoming light by a factor of 800. Enhancement is confirmed by
      photothermally induced bistability of these peaks even at sub-milliwatt input
      powers with as much as a four-fold difference in the magnitude of their
      responses. The strong field intensities of these modes could significantly
      enhance desired nonlinear optical responses in fiber, provided the impact of
      absorption is addressed.

PMID- 24562224
TI  - Adiabatic pulse propagation in a dispersion-increasing fiber for spectral
      compression exceeding the fiber dispersion ratio limitation.
AB  - Adiabatic soliton spectral compression in a dispersion-increasing fiber (DIF)
      with a linear dispersion ramp is studied both numerically and experimentally. The
      anticipated maximum spectral compression ratio (SCR) would be limited by the
      ratio of the DIF output to the input dispersion values. However, our numerical
      analyses indicate that SCR greater than the DIF dispersion ratio is feasible,
      provided the input pulse duration is shorter than a threshold value along with
      adequate pulse energy control. Experimentally, a SCR of 28.6 is achieved in a 1
      km DIF with a dispersion ratio of 22.5.

PMID- 24562225
TI  - High-sensitivity temperature sensing using higher-order Stokes stimulated
      Brillouin scattering in optical fiber.
AB  - In an effort to reduce the cost of sensing systems and make them more compact and
      flexible, Brillouin scattering has been demonstrated as a useful tool, especially
      for distributed temperature and strain sensing (DTSS), with a resolution of a few
      centimeters over several tens of kilometers of fiber. However, sensing is limited
      by the Brillouin frequency shift's sensitivity to these parameters, which are of
      the order of ~1.3  MHz/ degrees C and of ~0.05  MHz/MUepsilon for standard fiber.
      In this Letter, we demonstrate a new and simple technique for enhancing the
      sensitivity of sensing by using higher-orders Stokes shifts with stimulated
      Brillouin scattering (SBS). By this method, we multiply the sensitivity of the
      sensor by the number of the Stokes order used, enhanced by six-fold, therefore
      reaching a sensitivity of ~7  MHz/ degrees C, and potentially ~0.30 
      MHz/MUepsilon. To do this, we place the test fiber within a cavity to produce a
      frequency comb. Based on a reference multiorder SBS source for heterodyning, this
      system should provide a new distributed sensing technology with significantly
      better resolution at a potentially lower cost than currently available DTSS
      systems.

PMID- 24562226
TI  - Simple technique for integrating compact silicon devices within optical fibers.
AB  - In this work, we present a simple fabrication process enabling the integration of
      a subwavelength amorphous silicon layer inside optical fibers by means of the arc
      discharge technique. To assess our method, we have fabricated a compact in-line
      Fabry-Perot interferometer consisting of a thin (<1  MUm) a-Si:H layer completely
      embedded within a standard single-mode optical fiber. The device exhibits low
      loss (1.3 dB) and high interference fringe visibility (~80%) both in reflection
      and transmission, due to the high refractive index contrast between silica and a
      Si:H. A high linear temperature sensitivity up to 106  pm/ degrees C is
      demonstrated in the range 120 degrees C-400 degrees C. The proposed
      interferometer is attractive for point monitoring applications as well as for
      ultrahigh-temperature sensing in harsh environments.

PMID- 24562227
TI  - Simultaneous 0.8, 1.0, and 1.3 MUm multispectral and common-path broadband source
      for optical coherence tomography.
AB  - Simultaneous multispectral generation in 0.8, 1.0, and 1.3 MUm wavelength ranges
      by efficient energy conversions of 1.0 MUm wavelength femtosecond pulses through
      a nonlinear fiber was reported. The output spectral range of this multispectral
      light source was composed of 0.6-0.9 MUm blue-shifted Cherenkov radiation (CR),
      1.0 MUm residual pump, and 1.1-1.7 MUm red-shifted soliton self-frequency shift
      (SSFS) with more than 1  mW/nm power-spectral densities. Output characteristics
      of the multispectral light source were then quantitatively analyzed and the
      central wavelengths of CR and SSFS emissions can be further easily adjusted by
      changing the input power into wavelength conversion fiber. Example spectral
      domain optical coherence tomography (OCT) images of an IR card and finger skin
      were also performed with the demonstrated source. Due to the advantages of its
      simplicity, easily operated, and wavelength tunability, the reported
      multispectral source could be widely applicable for various spectroscopic OCT
      applications.

PMID- 24562228
TI  - Axial nanoscale localization by normalized total internal reflection fluorescence
      microscopy.
AB  - We present a simple modification of a standard total internal reflection
      fluorescence microscope to achieve nanometric axial resolution, typically ~10 
      nm. The technique is based on a normalization of total internal reflection images
      by conventional epi-illumination images. We demonstrate the potential of our
      method to study the adhesion of phopholipid giant unilamellar vesicles.

PMID- 24562229
TI  - Dressing plasmon resonance with particle-microcavity architecture for efficient
      nano-optical trapping and sensing.
AB  - We propose a particle-microcavity scheme for efficient optical trapping and
      sensing. When a resonant plasmonic nanoparticle (NP) is placed inside a
      microcavity with high Q-factor, sensitivity is enhanced in the far-field
      extinction while near-field around the NP is barely affected. Stable near-field
      and high sensitivity for optical trapping and ultrasensitive detection of
      nanosized targets are therefore realized simultaneously. Such a particle
      microcavity system opens up a new hybrid nanophotonic device platform that
      combines the unique merits of conventional and plasmonic integrated photonics. 

PMID- 24562230
TI  - Single-shot x-ray phase imaging with grating interferometry and photon-counting
      detectors.
AB  - In this Letter, we present a single-shot approach to quantitatively retrieve x
      ray absorption and phase shift in grating interferometry. The proposed approach
      makes use of the energy-resolving capability of x-ray photon-counting detectors.
      The retrieval method is derived and presented and is tested based on numerical
      simulations, including photon shot noise. The good agreement between retrieval
      results and theoretical values confirms the feasibility of the presented
      approach. 

PMID- 24562231
TI  - Measurement-device-independent quantum key distribution with modified coherent
      state.
AB  - The measurement-device-independent quantum key distribution (MDI-QKD) protocol
      has been proposed for the purpose of removing the detector side channel attacks.
      Due to the multiphoton events of coherent states sources, real-life
      implementations of MDI-QKD protocol must employ decoy states to beat the photon
      number-splitting attack. Decoy states for MDI-QKD based on the weak coherent
      states (WCSs) have been studied recently. In this Letter, we propose to perform
      MDI-QKD protocol with modified coherent states (MCS) sources. We simulate the
      performance of MDI-QKD with the decoy states based on MCS sources. And our
      simulation indicates that both the secure-key rate and transmission distance can
      be improved evidently with MCS sources. The physics behind this improvement is
      that the probability of multiphoton events of the MCS is lower than that of WCSs
      while at the same time the probability of single-photon is higher. 

PMID- 24562232
TI  - Designing slow-light photonic crystal waveguides for four-wave mixing
      applications.
AB  - We discuss the optimization of photonic crystal waveguides for four-wave mixing
      (FWM) applications, taking into account linear loss and free-carrier effects.
      Suitable figures of merit are introduced in order to guide us through the choice
      of practical, high-efficiency designs requiring relatively low pump power and
      small waveguide length. In order to realistically perform the waveguide
      optimization process, we propose and validate an approximate expression for the
      FWM efficiency, which significantly alleviates our numerical calculations.
      Promising waveguide designs are identified by means of an exhaustive search,
      altering some structural parameters. Our approach aims to optimize the waveguides
      for nonlinear signal-processing applications based on the FWM. 

PMID- 24562233
TI  - Distribution of high-stability 10 GHz local oscillator over 100 km optical fiber
      with accurate phase-correction system.
AB  - We have developed a radio-frequency local oscillator remote distribution system,
      which transfers a phase-stabilized 10.03 GHz signal over 100 km optical fiber.
      The phase noise of the remote signal caused by temperature and mechanical stress
      variations on the fiber is compensated by a high-precision phase-correction
      system, which is achieved using a single sideband modulator to transfer the phase
      correction from intermediate frequency to radio frequency, thus enabling accurate
      phase control of the 10 GHz signal. The residual phase noise of the remote 10.03
      GHz signal is measured to be -70  dBc/Hz at 1 Hz offset, and long-term stability
      of less than 1*10-16 at 10,000 s averaging time is achieved. Phase error is less
      than +/-0.03pi.

PMID- 24562234
TI  - Geometric definition of the V-parameter in photonic crystal fibers.
AB  - We propose a general geometric definition of the V-parameter in photonic crystal
      fibers (PCF). We argue that the fundamental modal field in both square-lattice
      and triangular-lattice PCFs can be approached by certain proper assemblies of the
      fundamental mode in a one-dimensional planar waveguide. This observation suggests
      a geometric definition of the effective core radius and the single-mode regime of
      V<=pi/2 in various PCFs. The numerical results imply that the suggestion is valid
      for all of the one-rod, seven-rod, 19-rod, and 37-rod core triangular-lattice
      PCFs and the one-rod, nine-rod, and 25-rod core square-lattice PCFs. 

PMID- 24562235
TI  - Tamm-plasmon and surface-plasmon hybrid-mode based refractometry in photonic
      bandgap structures.
AB  - The transverse magnetic (TM) polarized hybrid modes formed as a consequence of
      coupling between Tamm plasmon polariton (TM-TPP) mode and surface plasmon
      polariton (SPP) mode exhibit interesting dispersive features for realizing a
      highly sensitive and accurate surface plasmon resonance (SPR) sensor. We found
      that the TM-TPP modes, formed at the interface of distributed Bragg reflector and
      metal, are strongly dispersive as compared to SPP modes at optical frequencies.
      This causes an appreciably narrow interaction bandwidth between TM-TPP and SPP
      modes, which leads to highly accurate sensing. In addition, appropriate tailoring
      of dispersion characteristics of TM-TPP as well as SPP modes could ensure high
      sensitivity of a novel SPR platform. By suitably designing the Au/TiO2/SiO2-based
      geometry, we propose a TM-TPP/SPP hybrid-mode sensor and achieve a sensitivity
      >=900  nm/RIU with high detection accuracy (>=30  MUm-1) for analyte refractive
      indices varying between 1.330 and 1.345 in 600-700 nm wavelength range. The
      possibility to achieve desired dispersive behavior in any spectral band makes the
      sensing configuration an extremely attractive candidate to design sensors
      depending on the availability of optical sources.

PMID- 24562236
TI  - Fractional-length sync-pumped degenerate optical parametric oscillator for 500
      MHz 3-MUm mid-infrared frequency comb generation.
AB  - We demonstrate a mid-IR frequency comb centered at 3120 nm with 650-nm (20-THz)
      bandwidth at a comb-teeth spacing of 500 MHz. The generated comb is based on a
      compact ring-type synchronously pumped optical parametric oscillator (SPOPO)
      operating at degeneracy and pumped by a mode-locked Er-doped 1560 nm fiber laser
      at a repetition rate of 100 MHz. We achieve high-repetition rate by using a
      fractional-length cavity with a roundtrip length of 60 cm, which is one-fifth of
      the length dictated by conventional synchronous pumping.

PMID- 24562237
TI  - Laser Doppler projection tomography.
AB  - We propose a laser Doppler projection tomography (LDPT) method to obtain
      visualization of three-dimensional (3D) flowing structures. With LDPT, the
      flowing signal is extracted by a modified laser Doppler method, and the 3D
      flowing image is reconstructed by the filtered backprojection algorithm. Phantom
      experiments are performed to demonstrate that LDPT is able to obtain 3D flowing
      structure with higher signal-to-noise ratio and spatial resolution. Our
      experiment results display its potentially useful application to develop 3D label
      free optical angiography for the circulation system of live small animal models
      or microfluidic experiments. 

PMID- 24562238
TI  - Coherent emission at 537 nm from IR-pumped erbium-doped silica microspheres.
AB  - Low pump threshold upconversion narrowband emission at 537 nm in a simple system
      of erbium-doped silica microsphere at the tip of a fiber is reported. The
      emission comes out radially (not from whispering gallery modes) and is strongly
      enhanced by a thin metal coating, in particular with platinum. This enhancement
      seems to be related to the coupling with surface plasmons. The emission
      wavelength does not correspond to any energy level differences of erbium in
      silica, and is the same that was reported earlier in a coated fiber.

PMID- 24562239
TI  - High-power supercontinuum generation in a ZBLAN fiber with very efficient power
      distribution toward the mid-infrared.
AB  - We report high-power supercontinuum (SC) generation in a step-index
      fluorozirconate (ZBLAN) fiber with a zero-dispersion wavelength shifted to ~1.9 
      MUm. Pumping the fluoride fiber with 2.75 W of power provided by a thulium-doped
      fiber amplifier, a continuous spectrum extending from ~0.85 to 4.2 MUm with 2.24
      W of average output power was achieved. Over 61% (1.37 W) of the total output
      power corresponds to wavelengths longer than 3 MUm, which shows, to the best of
      our knowledge, the highest power conversion efficiency toward the mid-IR spectral
      band in relation to the output spectrum width. A linear SC power scalability up
      to 5.24 W, with a spectral band of ~0.9-4  MUm, with repetition rate and pump
      power provided by a 1.55 MUm fiber master-oscillator power amplifier system, is
      also demonstrated.

PMID- 24562240
TI  - Multichannel photon-pair generation using hydrogenated amorphous silicon
      waveguides.
AB  - We demonstrate highly efficient photon-pair generation using an 8 mm long
      hydrogenated amorphous silicon (a-Si:H) waveguide in far-detuned multiple
      wavelength channels simultaneously, measuring a coincidence-to-accidental ratio
      as high as 400. We also characterize the contamination from Raman scattering and
      show it to be insignificant over a spectrum span of at least 5 THz. Our results
      highlight a-Si:H as a potential high-performance, CMOS-compatible platform for
      large-scale quantum applications, particularly those based on the use of
      multiplexed quantum signals.

PMID- 24562241
TI  - Enhancement of near-infrared to near-infrared upconversion emission in the CeO2:
      Er3+, Tm3+, Yb3+ inverse opals.
AB  - In this Letter, CeO2: Er3+, Tm3+, Yb3+ inverse opal with near-infrared to near
      infrared upconversion emission was prepared by polystyrene colloidal crystal
      templates, and the influence of photonic bandgap on the upconversion emission was
      investigated. Comparing with the reference sample, suppression of the blue or red
      upconversion luminescence was observed in the inverse opals. It is interesting
      that the near-infrared upconversion emission located at about 803 nm was enhanced
      due to the inhibition of visible upconversion emission in the inverse opals.
      Additionally, the variety of upconversion emission mechanisms was observed and
      discussed in the CeO2: Er3+, Tm3+, Yb3+ inverse opals.

PMID- 24562242
TI  - Ultra-wideband microwave photonic phase shifter with a 360 degrees  tunable phase
      shift based on an erbium-ytterbium co-doped linearly chirped FBG.
AB  - A simple photonic approach to implementing an ultra-wideband microwave phase
      shifter based on an erbium-ytterbium (Er/Yb) co-doped linearly chirped fiber
      Bragg grating (LCFBG) is proposed and experimentally demonstrated. The LCFBG is
      designed to have a constant magnitude response over a reflection band, and a
      phase response that is linear and nonlinear in two sections in the reflection
      band. When an optical single-sideband with carrier (OSSB+C) signal is sent to the
      LCFBG, by locating the optical carrier at the section corresponding to the
      nonlinear phase response and the sideband at the section corresponding to the
      linear phase response, a phase shift is introduced to the optical carrier, which
      is then translated to the microwave signal by beating the optical carrier and the
      sideband at a photodetector. The tuning of the phase shift is realized by
      optically pumping the Er/Yb co-doped LCFBG by a 980-nm laser diode. The proposed
      ultra-wideband microwave photonic phase shifter is experimentally demonstrated. A
      phase shifter with a full 360 degrees  phase shift with a bandwidth from 10 to 40
      GHz is experimentally demonstrated.

PMID- 24562244
TI  - Spatial filtering by axisymmetric photonic microstructures.
AB  - We propose and show experimentally axisymmetric spatial (angular) filtering of
      two-dimensional light beams by axisymmetric photonic microstructures. Such three
      dimensional microstructures (similar to photonic crystals), in gapless
      configuration, were recorded in bulk of glass, where the refractive index has
      been point-by-point modulated using tightly focused femtosecond laser pulses.
      Axisymmetric angular filtering of approximately 25 mrad is demonstrated
      experimentally.

PMID- 24562243
TI  - Zero focusing via competing nonlinearities in beta-barium-borate crystals.
AB  - We investigate nonlinear focusing behavior of light beams propagating in beta
      barium-borate crystals under mismatched second-harmonic generation. We clearly
      identify experimentally multiple self-focusing and defocusing regions against the
      orientation angle and the condition where competing quadratic and cubic
      nonlinearities perfectly compensate each other (zero-focusing point). 

PMID- 24562245
TI  - Enhancement and inhibition of light tunneling mediated by resonant mode
      conversion.
AB  - We show that the rate at which light tunnels between neighboring multimode
      waveguides can be drastically increased or reduced by the presence of small
      longitudinal periodic modulations of the waveguide properties that stimulate
      resonant conversion between the eigenmodes of each waveguide. Such a conversion,
      available only in multimode guiding structures, leads to periodic power transfer
      into higher-order modes, whose tails may considerably overlap with neighboring
      waveguides. As a result, the effective coupling constant for neighboring
      waveguides may change by several orders of magnitude upon small variations in the
      longitudinal modulation parameters. 

PMID- 24562246
TI  - Content-adaptive high-resolution hyperspectral video acquisition with a hybrid
      camera system.
AB  - We present a hybrid camera system that combines optical designs with
      computational processing to achieve content-adaptive high-resolution
      hyperspectral video acquisition. In particular, we record two video streams: one
      high-spatial resolution RGB video and one low-spatial resolution hyperspectral
      video in which the recorded points are dynamically selected using a spatial light
      modulator (SLM). Then through video-frame registration and a spatio-temporal
      spreading of the co-located spectral/RGB information, video with high spatial and
      spectral resolution is produced. The sampling patterns on the SLM are generated
      on-the-fly according to the scene content, which fully exploits the self
      adaptivity of the hybrid camera system. With an experimental prototype, we
      demonstrate significantly improved accuracy and efficiency as compared to the
      state-of-the-art. 

PMID- 24562247
TI  - On-chip silicon optical phased array for two-dimensional beam steering.
AB  - A 16-element optical phased array integrated on chip is presented for achieving
      two-dimensional (2D) optical beam steering. The device is fabricated on the
      silicon-on-insulator platform with a 250 nm silicon device layer. Steering is
      achieved via a combination of wavelength tuning and thermo-optic phase shifting
      with a switching power of P(pi)=20  mW per channel. Using a silicon waveguide
      grating with a polycrystalline silicon overlay enables narrow far field beam
      widths while mitigating the precise etching needed for conventional shallow etch
      gratings. Using this system, 2D steering across a 20 degrees *15 degrees  field
      of view is achieved with a sidelobe level better than 10 dB and with beam widths
      of 1.2 degrees *0.5 degrees .

PMID- 24562248
TI  - Mid-infrared difference-frequency generation in suspended GaAs waveguides.
AB  - We experimentally demonstrate mid-infrared difference-frequency generation in
      suspended 181 nm thick GaAs waveguides. Generation of the idler at wavelengths
      between 2800 and 3150 nm is enabled by form-birefringent phase-matching in
      ultrahigh index-contrast waveguides. Nonlinear mixing has a measured efficiency
      of 0.4  W-1 in a 1.2 mm long waveguide using a CW signal tunable between 1490 and
      1620 nm and a CW pump tunable between 1018 and 1032 nm at powers of a few mW.

PMID- 24562249
TI  - Unveiling square and triangular optical lattices: a comparative study.
AB  - We study square and triangular optical lattice formation using a diffraction
      technique with light-possessing orbital angular momentum (OAM). We demonstrate
      that it is possible to use Fraunhofer diffraction of light by a square aperture
      to unveil OAM about two times bigger than would be possible with a triangular
      aperture. We notice that the pattern remains truncated until a topological charge
      (TC) equal to 20 with good precision. Even though a square pattern cannot be used
      to determine the TC sign, it is possible to measure high order of the modulus and
      sign of the TC up to 20, combining patterns of the triangular and square
      apertures. 

PMID- 24562250
TI  - Photon pair generation and pump filtering in nonlinear adiabatic waveguiding
      structures.
AB  - We propose a novel integrated scheme for generation of Bell states, which allows
      simultaneous spatial filtering of pump photons. It is achieved through
      spontaneous parametric down-conversion in the system of nonlinear adiabatically
      coupled waveguides. We perform detailed analytic study of photon-pair generation
      in coupled waveguides and reveal the optimal conditions for the generation of
      each particular Bell state. Furthermore, we simulate the performance of the
      device under realistic assumptions and show that adiabatic coupling allows us to
      spatially filter the pump from modal-entangled photon pairs. Finally, we
      demonstrate that adiabatic couplers open the possibility of maintaining the
      purity of generated Bell states in a relatively fabrication-fault-tolerant way. 

PMID- 24562251
TI  - Atmospheric CH4 and N2O measurements near Greater Houston area landfills using a
      QCL-based QEPAS sensor system during DISCOVER-AQ 2013.
AB  - A quartz-enhanced photoacoustic absorption spectroscopy (QEPAS)-based gas sensor
      was developed for methane (CH4) and nitrous-oxide (N2O) detection. The QEPAS
      based sensor was installed in a mobile laboratory operated by Aerodyne Research,
      Inc. to perform atmospheric CH4 and N2O detection around two urban waste-disposal
      sites located in the northeastern part of the Greater Houston area, during
      DISCOVER-AQ, a NASA Earth Venture during September 2013. A continuous wave,
      thermoelectrically cooled, 158 mW distributed feedback quantum cascade laser
      emitting at 7.83 MUm was used as the excitation source in the QEPAS gas sensor
      system. Compared to typical ambient atmospheric mixing ratios of CH4 and N2O of
      1.8 ppmv and 323 ppbv, respectively, significant increases in mixing ratios were
      observed when the mobile laboratory was circling two waste-disposal sites in
      Harris County and when waste disposal trucks were encountered.

PMID- 24562252
TI  - Second harmonic generation in centrosymmetric gas with spatiotemporally focused
      intense femtosecond laser pulses.
AB  - We demonstrate unexpectedly strong second harmonic generation (SHG) in argon gas
      by use of spatio-temporally focused (SF) femtosecond laser pulses. The resulting
      SHG by the SF scheme at a 75 cm distance shows a significantly enhanced
      efficiency than that achieved with conventional focusing schemes, which offers a
      new promising possibility for standoff applications. Our theoretical calculations
      reasonably reproduce the experimental observations, which indicate that the
      observed SHG mainly originates from the gradient of non-uniform plasma
      dynamically controlled by the SF laser field. 

PMID- 24562253
TI  - Four-port integrated polarizing beam splitter.
AB  - In this Letter, we report on the first integrated four-port polarizing beam
      splitter. The device operates on the principle of mode evolution and was
      implemented in a silicon-on-insulator silicon photonics platform and fabricated
      on a 300 mm CMOS line using 193 nm optical immersion lithography. The adiabatic
      transition forming of the structure enabled over a 150 nm bandwidth from
      lambda~1350 to lambda~1500  nm, achieving a cross-talk level below -10  dB over
      the entire band.

PMID- 24562254
TI  - Trace gas absorption spectroscopy using functionalized microring resonators.
AB  - We detect trace gases at parts-per-billion levels using evanescent-field
      absorption spectroscopy in silicon nitride microring resonators coated with a
      functionalized sorbent polymer. An analysis of the microring resonance line
      shapes enables a measurement of the differential absorption spectra for a number
      of vapor-phase analytes. The spectra are obtained at the near-infrared overtone
      of OH-stretch resonance, which provides information about the toxicity of the
      analyte vapor. 

PMID- 24562255
TI  - Hybrid nanowedge plasmonic waveguide for low loss propagation with ultra-deep
      subwavelength mode confinement.
AB  - In this Letter, a novel waveguide based on hybrid surface plasmon polaritons
      (HSPPs) is proposed and numerically analyzed. This waveguide consists of two
      dielectric nanowires placed on both sides of a nanowedge-patterned metal film,
      which can confine light in the ultra-deep-subwavelength region (ranging from
      lambda2/4000 to lambda2/400) with a long propagation length (ranging from 1200 to
      3500 MUm). Compared to a previous HSPPs waveguide without the nanowedges, with
      the same propagation length, our proposed structure has much higher mode
      confinement with 1 order of magnitude smaller normalized mode area. An
      investigation of the effect of structural perturbations indicates that our
      proposed waveguide also has good tolerance of fabrication errors. The proposed
      waveguide could be an interesting alternative structure to realize nanolasers and
      optical trapping.

PMID- 24562256
TI  - Temperature effects in optical fiber dispersion compensation modules.
AB  - Differential group delay measurements of a fiber-based dispersion compensation
      module under different controlled temperature variations experience long
      birefringence relaxation times (>10  h) in response to temperature changes. These
      are interpreted here qualitatively with a stress strain behavioral model based on
      silica's viscoelastic property.

PMID- 24562257
TI  - Direct electron acceleration with tightly focused TM(0,1) beams: boundary
      conditions and non-paraxial corrections.
AB  - Non-paraxial corrections for a scalar optical field that follows the Helmotz
      equation are extracted for the first time, to the best of our knowledge, in the
      angular spectrum representation by taking into account generic boundary
      conditions. Those integration constants are compared with closed-form solutions
      and approximate series expansions usually obtained by other authors. This method
      is particularized to the direct electron acceleration with a tightly focused
      TM(0,1) laser beam to demonstrate that these constants have a strong effect on
      the final average energy and quality of the electron beam.

PMID- 24562258
TI  - Effect of resonator losses on the sensitivity of coupled resonator optical
      waveguide gyroscopes.
AB  - Recently there has been a growing interest in microphotonic integrated optical
      gyroscopes. Here, we analyze the effect of resonator losses on the rotational
      sensitivity of a coupled resonator optical waveguide (CROW) gyroscope in
      comparison to a single passive resonator gyroscope of the same size. We show that
      the CROW gyro offers a superior sensitivity only for very low propagation losses.
      Moreover, the single ring resonator gyro is found to have a sensitivity that is
      stable over wide range of resonator losses as well as boasting greater
      sensitivities than the CROW gyro for propagation losses in the resonators
      exceeding 10-1  dB/cm.

PMID- 24562259
TI  - Ultrashort pulses from an all-fiber ring laser incorporating a pair of chirped
      fiber Bragg gratings.
AB  - By incorporating two linearly chirped ultrabroadband fiber Bragg gratings of
      opposite dispersion in an all-fiber ring laser, we demonstrate a mode-locking
      regime in which a femtosecond pulse evolving in the normal dispersion gain
      segment is locally transformed into a highly chirped picosecond pulse that
      propagates in the remaining section of the cavity. By minimizing nonlinear
      effects and avoiding soliton pulse shaping in this anomalous-dispersion section,
      low repetition rate fiber lasers can be made to produce high-energy ultrashort
      pulses. Using this approach, 98 fs pulses with 0.96 nJ of energy are obtained
      from an erbium-doped fiber laser operated in the highly anomalous dispersion
      regime at a repetition rate of 9.4 MHz.

PMID- 24562260
TI  - Seven-core erbium-doped double-clad fiber amplifier pumped simultaneously by side
      coupled multimode fiber.
AB  - We demonstrate a seven-core erbium-doped fiber amplifier in which all the cores
      were pumped simultaneously by a side-coupled tapered multimode fiber. The
      amplifier has multicore (MC) MC inputs and MC outputs, which can be readily
      spliced to MC transmission fiber for amplifying space division multiplexed
      signals. Gain over 25 dB was obtained in each of the cores over a 40-nm bandwidth
      covering the C-band.

PMID- 24562261
TI  - Direct amplification of a nanosecond laser diode in a high gain diode-pumped
      Nd:YVO4 amplifier.
AB  - We demonstrate that Nd:YVO4 can efficiently amplify a nanosecond laser diode in a
      very simple double-pass configuration. Based on longitudinal pumping with a high
      brightness fiber-coupled laser diode at 808 nm (60 W, 100 MUm, 0.22 NA) and a low
      Nd-doped (0.2%) temperature controlled Nd:YVO4 we achieved an optical gain of 62
      dB with very low (<2%) parasitic laser emission and an average output power of 10
      W. At 15 kHz, we observed a strong gain saturation dynamic resulting in a pulse
      duration reduction from 100 to 3.5 ns. This effect enhances the peak power by a
      factor of 18 (130 kW) with an energy of 620 MUJ.

PMID- 24562262
TI  - Plasmon-enhanced four-wave mixing by nanoholes in thin gold films.
AB  - Nonlinear plasmonics opens up for wavelength conversion, reduced
      interaction/emission volumes, and nonlinear enhancement effects at the nanoscale
      with many compelling nanophotonic applications foreseen. We investigate nonlinear
      plasmonic responses of nanoholes in thin gold films by exciting the holes
      individually with tightly focused laser beams, employing a degenerated pump/probe
      and Stokes excitation scheme. Excitation of the holes results in efficient
      generation of both narrowband four-wave mixing (FWM) and broadband multiphoton
      excited luminescence, blueshifted relative to the excitation beams. Clear
      enhancements were observed when matching the pump/probe wavelength with the hole
      plasmon resonance. These observations show that the FWM generation is locally
      excited by nanoholes and has a resonant behavior primarily governed by the
      dimensions of the individual holes. 

PMID- 24562263
TI  - Tunable third-harmonic generation in a chalcogenide-tellurite hybrid optical
      fiber with high refractive index difference.
AB  - A chalcogenide-tellurite hybrid optical fiber with a step-index structure is
      fabricated by the rod-in-tube drawing technique. The core is made of 15Ge-3Ga
      12Sb-70S (mol. %) glass, and the cladding is made of 78TeO2-5ZnO-12Li2O-5Bi2O3
      (mol. %) glass. The refractive index difference Deltan=0.24. Tunable third
      harmonic generation from 568 to 869 nm is observed when the optical fiber is
      pumped by an optical parametric oscillator with the pump wavelength changing from
      1700 to 2600 nm.

PMID- 24562264
TI  - Cholesteric liquid crystal holographic laser.
AB  - A new type of lasing was obtained on the basis of a dye-doped cholesteric liquid
      crystal laser with transversally distributed excitation. Two coherent beams of
      the pumping laser formed an interference pattern in the planar dye-doped
      cholesteric layer and provided laser generation in the separate narrow strips of
      the pumped area. Each of the strips demonstrated lasing along the cholesteric
      axis. But, due to the mutual coherence of the separate strips emission, the total
      picture of lasing represented an interference pattern. Thus, in contrast to the
      conventional lasers, the intensity distribution in the laser emission pattern had
      a periodical character similar to diffraction from an elementary dynamic
      hologram. 

PMID- 24562265
TI  - Retardance and flicker modeling and characterization of electro-optic linear
      retarders by averaged Stokes polarimetry.
AB  - A polarimetric method for the measurement of linear retardance in the presence of
      phase fluctuations is presented. This can be applied to electro-optic devices
      behaving as variable linear retarders. The method is based on an extended Mueller
      matrix model for the linear retarder containing the time-averaged effects of the
      instabilities. As a result, an averaged Stokes polarimetry technique is proposed
      to characterize both the retardance and its flicker magnitude. Predictive
      capability of the approach is experimentally demonstrated, validating the model
      and the calibration technique. The approach is applied to liquid crystal on
      silicon displays (LCoS) using a commercial Stokes polarimeter. Both the magnitude
      of the average retardance and the amplitude of its fluctuation are obtained for
      each gray level value addressed, thus enabling a complete phase characterization
      of the LCoS. 

PMID- 24562266
TI  - Structured illumination diffraction phase microscopy for broadband,
      subdiffraction resolution, quantitative phase imaging.
AB  - Structured illumination microscopy (SIM) is an established technique that allows
      subdiffraction resolution imaging by heterodyning high sample frequencies into
      the system's passband via structured illumination. However, until now, SIM has
      been typically used to achieve subdiffraction resolution for intensity-based
      imaging. Here, we present a novel optical setup that uses structured illumination
      with a broadband light source to obtain noise-reduced, subdiffraction resolution,
      quantitative phase imaging (QPM) of cells. We compare this with a previous work
      for subdiffraction QPM imaging via SIM that used a laser source, and was thus
      still corrupted by coherent noise. 

PMID- 24562268
TI  - Role of cavity degeneracy for high-order mode excitation in end-pumped solid
      state lasers.
AB  - The possibility of exciting laser modes such as Laguerre-Gaussian (LG) or Ince
      Gaussian (IG) modes is discussed on the basis of a gain-matching integral. We
      reach the conclusion that, using tight pumping and away from degeneracy regions,
      only the IG(n,n)(e) modes can be excited. Furthermore, pure high-order modes with
      circular or elliptical nodal lines can never be excited. Only an approximation of
      such modes, which we call quasi-IG or quasi-LG modes, can be observed and only
      when the cavity is partially degenerate. We provide experimental results in
      perfect agreement with the theory and discuss the exact nature of the profiles
      observed at degeneracy in our experiments and elsewhere in the literature.

PMID- 24562267
TI  - Self-similar erbium-doped fiber laser with large normal dispersion.
AB  - We report a large normal dispersion erbium-doped fiber laser with self-similar
      pulse evolution in the gain fiber. The cavity is stabilized by the local
      nonlinear attractor in the gain fiber through the use of a narrow filter.
      Experimental results are accounted for by numerical simulations. This laser
      produces 3.5 nJ pulses, which can be dechirped to 70 fs with an external grating
      pair.

PMID- 24562269
TI  - Competition between stimulated Raman and Brillouin scattering processes in CF4
      gas.
AB  - CF4 gas has a relatively high Raman cross section and a relatively small Raman
      shift and is an excellent candidate for a gas-filled hollow-core photonic bandgap
      (HC-PBG) fiber Raman wavelength converter. Here we investigate experimentally the
      onset and competition between stimulated Raman scattering (SRS) and stimulated
      Brillouin scattering (SBS) processes in high-pressure CF4 gas. We focus 532 nm
      laser pulses into a high-pressure gas cell and measure the SBS and SRS response.
      The thresholds for both processes decrease with pressure, as expected. However,
      with short focusing geometries, the SBS threshold is lower than the SRS
      threshold, and with long focusing geometries, it is the opposite. We further show
      that with HC-PBG fiber geometry SRS dominates.

PMID- 24562270
TI  - Recovery of Schell-model partially coherent beams.
AB  - Partially coherent light is often preferable to its completely coherent
      counterpart in applications such as imaging, sensing, and free-space optical
      communications. To fully exploit its advantages, techniques able to retrieve
      information carried by the beam are required. Here, we develop and experimentally
      demonstrate a phase-space optics technique for complete spatial analysis of
      widely used Schell-model beams. It allows for fast information recovery and can
      be applied for quantitative phase imaging of objects under partially coherent
      illumination. 

PMID- 24562271
TI  - Coherence measurement with digital micromirror device.
AB  - We measure the complex-valued spatial coherence function of a multimode broad
      area laser diode using Young's classical double slit experiment realized with a
      digital micromirror device. We use this data to construct the coherent modes of
      the beam and to simulate its propagation before and after the measurement plane.
      When comparing the results to directly measured intensity profiles, we find
      excellent correspondence to the extent that even small details of the beam can be
      predicted. We also consider the number of measurement points required to model
      the beam with sufficient accuracy. 

PMID- 24562272
TI  - Suppression of thermal frequency noise in erbium-doped fiber random lasers.
AB  - Frequency and intensity noise are characterized for erbium-doped fiber (EDF)
      random lasers based on Rayleigh distributed feedback mechanism. We propose a
      theoretical model for the frequency noise of such random lasers using the
      property of random phase modulations from multiple scattering points in ultralong
      fibers. We find that the Rayleigh feedback suppresses the noise at higher
      frequencies by introducing a Lorentzian envelope over the thermal frequency noise
      of a long fiber cavity. The theoretical model and measured frequency noise agree
      quantitatively with two fitting parameters. The random laser exhibits a noise
      level of 6  Hz2/Hz at 2 kHz, which is lower than what is found in conventional
      narrow-linewidth EDF fiber lasers and nonplanar ring laser oscillators (NPROs) by
      a factor of 166 and 2, respectively. The frequency noise has a minimum value for
      an optimum length of the Rayleigh scattering fiber.

PMID- 24562273
TI  - Pulse compression grating fabrication by diffractive proximity photolithography.
AB  - We report about a newly devised throughput-scalable fabrication method for high
      quality periodic submicron structures. The process is demonstrated for optical
      transmission gratings in fused silica with a period of 800 nm (1250  lines/mm) to
      be used in laser pulse compression. The technology is based on an innovative
      advancement of i-line proximity photolithography performed in a mask aligner. The
      aerial image is encoded in a rigorously optimized electron-beam-written three
      level phase mask which is illuminated by an adapted multipole configuration of
      incidence angles. In comparison to conventional proximity lithography, the
      process enables a significantly higher resolution while maintaining a good depth
      of focus--in contrast to lithography based on direct Talbot-imaging. Details
      about the grating fabrication process and characterization of fabricated pulse
      compression grating wafers are presented. The gratings show a diffraction
      efficiency of 97% at a wavelength of 1030 nm and a wavefront error comparable to
      gratings fabricated by electron-beam lithography.

PMID- 24562274
TI  - Supercontinuum generation in an on-chip silica waveguide.
AB  - Supercontinuum generation is demonstrated in an on-chip silica spiral waveguide
      by launching 180 fs pulses from an optical parametric oscillator at the center
      wavelength of 1330 nm. With a coupled pulse energy of 2.17 nJ, the broadest
      spectrum in the fundamental TM mode extends from 936 to 1888 nm (162 THz) at -50 
      dB from peak. There is a good agreement between the measured spectrum and a
      simulation using a generalized nonlinear Schrodinger equation.

PMID- 24562275
TI  - Energy scaling of femtosecond amplifiers using actively controlled divided-pulse
      amplification.
AB  - Divided-pulse amplification is a promising method for the energy scaling of
      femtosecond laser amplifiers, where pulses are temporally split prior to
      amplification and coherently recombined afterwards. We present a method that uses
      an actively stabilized setup with separated stages for splitting and combining.
      The additional degrees of freedom can be employed to mitigate the limitations
      originating from saturation of the amplifier that cannot be compensated in
      passive double-pass configurations using just one common stage for pulse
      splitting and combining. In a first proof-of-principle experiment, actively
      controlled divided pulses are applied in a fiber chirped-pulse amplification
      system resulting in combined and compressed pulses with an energy of 1.25 mJ and
      a peak power of 2.9 GW.

PMID- 24562277
TI  - Optical rogue waves generated on Gaussian background beam.
AB  - We study optical rogue waves (RWs) in a nonlinear graded-index waveguide with
      variable coefficients. An exact RW solution on Gaussian background beam is
      presented, in contrast to the previous studies about RWs, on plane wave
      background. It is shown that the characteristics of RWs are maintained on
      Gaussian background beam and that the beam's width is even a bit smaller than the
      RWs scale. These results may raise the possibility of related experiments and
      potential applications in nonlinear optics. 

PMID- 24562276
TI  - OPTiSPIM: integrating optical projection tomography in light sheet microscopy
      extends specimen characterization to nonfluorescent contrasts.
AB  - Mesoscopic 3D imaging has become a widely used optical imaging technique to
      visualize intact biological specimens. Selective plane illumination microscopy
      (SPIM) visualizes samples up to a centimeter in size with micrometer resolution
      by 3D data stitching but is limited to fluorescent contrast. Optical projection
      tomography (OPT) works with fluorescent and nonfluorescent contrasts, but its
      resolution is limited in large samples. We present a hybrid setup (OPTiSPIM)
      combining the advantages of each technique. The combination of fluorescent and
      nonfluorescent high-resolution 3D data into integrated datasets enables a more
      extensive representation of mesoscopic biological samples. The modular concept of
      the OPTiSPIM facilitates incorporation of the transmission OPT modality into
      already established light sheet based imaging setups. 

PMID- 24562278
TI  - Polycrystalline silicon ring resonator photodiodes in a bulk complementary metal
      oxide-semiconductor process.
AB  - We present measurements on resonant photodetectors utilizing sub-bandgap
      absorption in polycrystalline silicon ring resonators, in which light is
      localized in the intrinsic region of a p+/p/i/n/n+ diode. The devices, operating
      both at lambda=1280 and lambda=1550  nm and fabricated in a complementary metal
      oxide-semiconductor (CMOS) dynamic random-access memory emulation process,
      exhibit detection quantum efficiencies around 20% and few-gigahertz response
      bandwidths. We observe this performance at low reverse biases in the range of a
      few volts and in devices with dark currents below 50 pA at 10 V. These results
      demonstrate that such photodetector behavior, previously reported by Preston et
      al. [Opt. Lett. 36, 52 (2011)], is achievable in bulk CMOS processes, with
      significant improvements with respect to the previous work in quantum efficiency,
      dark current, linearity, bandwidth, and operating bias due to additional midlevel
      doping implants and different material deposition. The present work thus offers a
      robust realization of a fully CMOS-fabricated all-silicon photodetector
      functional across a wide wavelength range.

PMID- 24562279
TI  - Observation of accelerating Wannier-Stark beams in optically induced photonic
      lattices.
AB  - We generate optical beams analogous to the Wannier-Stark states in semiconductor
      superlattices and observe that the two main lobes of the WS beams self-bend
      (accelerate) along two opposite trajectories in a uniform one-dimensional
      photonic lattice. Such self-accelerating features exist only in the presence of
      the lattice and are not observed in a homogenous medium. Under the action of
      nonlinearity, however, the beam structure and acceleration cannot be preserved.
      Our experimental observations are in qualitative agreement with theoretical
      predictions. 

PMID- 24562280
TI  - Long-haul self-mixing interference and remote sensing of a distant moving target
      with a thin-slice solid-state laser.
AB  - An effective long-haul self-mixing interference effect has been observed in a
      thin-slice LiNdP4O12 (LNP) laser due to Doppler-shifted optical feedback from a
      distant target. The narrow spectral linewidth of the LNP laser, which was
      evaluated to be 16 kHz by heterodyne measurements, led to successful self-mixing
      laser Doppler velocimetry and vibrometry of targets placed 2.5 km away from the
      laser through single-mode optical fiber access.

PMID- 24562281
TI  - Isotropic bicomponent partially polarized and partially coherent light.
AB  - The degree of coherence of scalar light remains constant when the fields are
      modified by the same random linear transformation, which can be represented by
      the multiplication by a random complex number. This shows that the coherence
      properties of scalar light at order two are not modified with the increase of
      disorder of each field that results from these transformations. We analyze the
      generalization of this property to partially polarized light. We determine the
      class of fields that can possess this property for any couple of points in a
      space-frequency or space-time domain after modification with deterministic Jones
      transformations. We show that the second-order coherence properties of this class
      of light can be generated experimentally with two uncorrelated totally polarized
      sources that have the same scalar coherence properties. 

PMID- 24562282
TI  - Ultrashort silica liquid crystal photonic crystal fiber polarization rotator.
AB  - In this Letter, an ultra-compact polarization rotator (PR) based on silica
      photonic crystal fiber with liquid crystal core is introduced and analyzed using
      full-vectorial finite difference approaches. The analyzed parameters of the
      suggested PR are the conversion length, modal hybridness, power conversion and
      crosstalk. In addition, the fabrication tolerance analysis of the reported design
      is investigated in detail. The proposed PR has an ultra-compact device length of
      4.085 MUm and an almost 100% polarization conversion ratio.

PMID- 24562283
TI  - Offner radial group delay compensator for ultra-broadband laser beam transport.
AB  - Conventional lens-based image relays introduce radial group delay that
      significantly reduces focal-spot intensity of ultra-broadband short pulses. A
      direct compensation scheme that can be used with conventional singlet image
      relays is proposed. The compensation scheme is based on using two negative lenses
      embedded within an Offner imaging system. The setup allows a single-pass
      configuration and eliminates the need for polarization switching optics. The
      performance of this setup is calculated using ray tracing. The compensation
      improves the spatiotemporal Strehl ratio from 0.02 to 0.97. 

PMID- 24562284
TI  - Comb transmission filters defined by phase-shifted superstructure Bragg gratings.
AB  - We present a design method and numerical results describing the construction of
      distributed feedback grating filters that support discrete combs of transmission
      resonances. These filter designs define open superstructure grating resonators
      with transmission channels that can be placed at predetermined frequencies, such
      as those defined by the wavelength division multiplexing grid or by a secondary
      frequency comb source. Focusing on a specific example with 40 GHz channel
      spacing, we optimize an active structure that defines three low-threshold lasing
      modes. How our design approach relates to filter synthesis techniques based on
      cascaded grating resonators is also discussed.

PMID- 24562285
TI  - Airy-like beam transverse acceleration control by rainbow effect.
AB  - We propose and numerically analyze the transverse acceleration control for the
      Airy-like beams from incomplete Airy waveguide and Airy waveguide by rainbow
      effect. We show that the Airy-like beams have an obvious change in transverse
      acceleration with a slight variation (10 nm) in incident wavelength. The rainbow
      phenomenon is introduced to study the Airy-like beam propagation with a different
      wavelength. The equivalent initial launch angle is also considered to explain
      transverse acceleration of the Airy-like beams.

PMID- 24562286
TI  - Propagation of a squeezed optical field in a medium with superluminal group
      velocity.
AB  - We investigated the propagation of a squeezed optical field, generated via the
      polarization self-rotation effect, with a sinusoidally modulated degree of
      squeezing through an atomic medium with anomalous dispersion. We observed the
      advancement of the signal propagating through a resonant Rb vapor compared to the
      reference signal, propagating in air. The measured advancement time grew linearly
      with atomic density, reaching a maximum of 11+/-1  MUs, which corresponded to a
      negative group velocity of v(g)~-7,000  m/s. We also confirmed that the
      increasing advancement was accompanied by a reduction of output squeezing levels
      due to optical losses, in good agreement with theoretical predictions.

PMID- 24562287
TI  - Single-mode pumped high air-fill fraction photonic crystal fiber taper for high
      power deep-blue supercontinuum sources.
AB  - Dispersion control with axially nonuniform photonic crystal fibers (PCFs) permits
      supercontinuum (SC) generation into the deep-blue from an ytterbium pump laser.
      In this Letter, we exploit the full degrees of freedom afforded by PCFs to
      fabricate a fiber with longitudinally increasing air-fill fraction and decreasing
      diameter directly on the draw-tower. We demonstrate SC generation extending down
      to 375 nm in one such monolithic fiber device that is single-mode at 1064 nm at
      the input end.

PMID- 24562288
TI  - Generation of radially polarized Bessel-Gaussian beams from c-cut Nd:YVO4 laser.
AB  - We experimentally demonstrate the generation of radially polarized Bessel
      Gaussian beams from a c-cut Nd:YVO4 laser with a hemispherical cavity
      configuration by proper mode control. The output beam has an annular-shaped
      intensity distribution with radial polarization. When the beam is focused, the
      intensity pattern changes to a multi-ring, which is a typical characteristic of
      the lowest transverse mode of vector Bessel-Gaussian beam. Higher-order modes of
      vector Bessel-Gaussian beam are also observed from the same cavity by slightly
      changing the cavity alignment. The experimental results show a good agreement
      with the simulation results for both focal and far fields. The present method is
      a simple and direct way for generating vector Bessel-Gaussian beams.

PMID- 24562289
TI  - People Claim Objectivity After Knowingly Using Biased Strategies.
AB  - People tend not to recognize bias in their judgments. Such "bias blindness"
      persists, we show, even when people acknowledge that the judgmental strategies
      preceding their judgments are biased. In Experiment 1, participants took a test,
      received failure feedback, and then were led to assess the test's quality via an
      explicitly biased strategy (focusing on the test's weaknesses), an explicitly
      objective strategy, or a strategy of their choice. In Experiments 2 and 3,
      participants rated paintings using an explicitly biased or explicitly objective
      strategy. Across the three experiments, participants who used a biased strategy
      rated it as relatively biased, provided biased judgments, and then claimed to be
      relatively objective. Participants in Experiment 3 also assessed how biased they
      expected to be by their strategy, prior to using it. These pre-ratings revealed
      that not only did participants' sense of personal objectivity survive using a
      biased strategy, it grew stronger.

PMID- 24562290
TI  - Can the learning curve of totally endoscopic robotic mitral valve repair be short
      circuited?
AB  - OBJECTIVE: A concern with the initiation of totally endoscopic robotic mitral
      valve repair (TERMR) programs has been the risk for the learning curve. To
      minimize this risk, we initiated a TERMR program with a defined team and
      structured learning approach before clinical implementation. METHODS: A dedicated
      team (two surgeons, one cardiac anesthesiologist, one perfusionist, and two
      nurses) was trained with clinical scenarios, simulations, wet laboratories, and
      "expert" observation for 3 months. This team then performed a series of TERMRs of
      varying complexity. RESULTS: Thirty-two isolated TERMRs were performed during the
      first programmatic year. All operations included mitral valve repair, left atrial
      appendage exclusion, and annuloplasty device implantation. Additional procedures
      included leaflet resection, neochordae insertion, atrial ablation, and papillary
      muscle shortening. Longer clamp times were associated with number of neochordae
      (P < 0.01), papillary muscle procedures (P < 0.01), and leaflet resection (P =
      0.06). Sequential case number had no impact on cross-clamp time (P = 0.3).
      Analysis of nonclamp time demonstrated a 71.3% learning percentage (P < 0.01; ie,
      28.7% reduction in nonclamp time with each doubling of case number). There were
      no hospital deaths or incidences of stroke, myocardial infarction, unplanned
      reoperation, respiratory failure, or renal failure. Median length of stay was 4
      days. All patients were discharged home. CONCLUSIONS: Totally endoscopic robotic
      mitral valve repair can be safely performed after a pretraining regimen with
      emphasis on experts' current practice and team training. After a pretraining
      regimen, cross-clamp times were not subject to learning curve phenomena but were
      dependent on procedural complexity. Nonclamp times were associated with a short
      learning curve.

PMID- 24562291
TI  - Minimally invasive delivery of a novel direct epicardial assist device in a
      porcine heart failure model.
AB  - OBJECTIVE: Despite advances in design, modern ventricular assist device placement
      involves median sternotomy and cardiopulmonary bypass and is associated with
      infectious/embolic complications. In this study, we examine the feasibility and
      function of a novel minimally invasive, non-blood-contacting epicardial assist
      device in a porcine ischemic cardiomyopathy model. METHODS: Feasibility was first
      tested in an ex vivo thoracoscopic trainer box with slaughterhouse hearts. Five
      male Yorkshire swine underwent selective ligation of the circumflex artery to
      create a posterolateral infarct Twelve weeks after infarct, all animals underwent
      left minithoracotomy. A custom inflatable bladder was positioned over the
      epicardial surface of the infarct and firmly secured to the surrounding border
      zone myocardium with polypropylene mesh and minimally invasive mesh tacks. An
      external gas pulsation system actively inflated and deflated the bladder in
      synchrony with the cardiac cycle. All animals then underwent cardiac magnetic
      resonance imaging to assess ventricular function. RESULTS: All subjects
      successfully underwent off-pump placement of the epicardial assist device via
      minithoracotomy. Ejection fraction significantly improved from 29.1% +/- 4.8% to
      39.6% +/- 4.23% (P < 0.001) when compared with pretreatment. End-systolic volume
      decreased (76.6 +/- 13.3 mL vs 62.4 +/- 12.0 mL, P < 0.001) and stroke volume
      increased (28.6 +/- 3.4 mL vs 37.9 +/- 3.1 mL, P < 0.05) when assisted. No change
      was noted in end-diastolic volume (105.1 +/- 11.4 vs 100.3 +/- 12.7). On
      postmortem examination, mesh fixation and device position were excellent in all
      cases. No adverse events were encountered. CONCLUSIONS: Directed epicardial
      assistance improves ventricular function in a porcine ischemic cardiomyopathy
      model and may provide a safe alternative to currently available ventricular
      assist device therapies. Further, the technique used for device positioning and
      fixation suggests that an entirely thoracoscopic approach is possible.

PMID- 24562292
TI  - Economic and operational implications of a standardized approach to hemodynamic
      support therapy using percutaneous cardiac assist devices.
AB  - OBJECTIVE: Impella 2.5 has been shown to reduce major adverse events for patients
      undergoing elective high-risk percutaneous coronary intervention. We performed a
      single-center retrospective study to compare the costs and resource use of
      Impella 2.5 and intra-aortic balloon pump (IABP) support. METHODS: All high-risk
      patients who received Impella 2.5 (n = 35) and IABP (n = 295) support from
      December 2008 to July 2011 were included. Propensity score matching identified a
      balanced 1:1 matched cohort (35 Impella vs 35 IABP) based on indications for
      implantation, preimplantation hemodynamics, and age. Diagnostic, procedural,
      financial, and resource use data were collected. RESULTS: As compared with IABP,
      Impella offered a more predictable course of treatment/resource consumption and
      was not associated with any extreme cost outliers (17.1% vs 0.0%, respectively; P
      = 0.025). The mean admission and 90-day episode of care total costs for Impella
      were 5.5% ($67,681 vs $71,608, P = 0.79) and 4.2% ($70,680 vs $73,476, P = 0.85)
      lesser than that for IABP, respectively. Although not statistically significant,
      Impella patients had a trend toward lower rehospitalization rates (11.4% vs 20%),
      lesser mean index length of hospital stay (11.2 vs 13.7), and 90-day (11.7 vs
      14.2) episode of care length of hospital stay. CONCLUSIONS: Impella support was
      associated with consistent course of treatment/resource consumption with
      significantly fewer 90-day extreme cost outliers than was IABP. The lower index
      and 90-day follow-up cost trends observed for Impella were driven by shorter
      length of hospital stay and fewer rehospitalizations. As providers strive to
      improve quality of care by reducing variability, these findings have implications
      for the development of hemodynamic support algorithms.

PMID- 24562293
TI  - Left ventricular pseudoaneurysm after left ventricular remodeling: port access
      approach.
AB  - Cases of left ventricular pseudoaneurysm caused by patch leakage after left
      ventricular remodeling are quite rare. We describe the case of a 66-year-old man
      operated on through a left thoracotomy using the Port Access platform to treat
      patch detachment after left ventricular remodeling. 

PMID- 24562294
TI  - Faster photoinduced electron transfer in a diluted mixture than in a neat donor
      solvent: effect of excited-state H-bonding.
AB  - In a neat electron-donating solvent (in this case aniline), photoinduced electron
      transfer (PET) from the solvent to an excited acceptor (e.g. a coumarin
      fluorophore) may be anticipated to be the most efficient because of the close
      contact of the acceptor with many donors. Addition of an inert component would
      most likely retard the PET process by replacing some donors from the
      neighbourhood of the acceptors. Surprisingly, we found dramatic acceleration of
      PET (6-10 fold enhancement compared to neat aniline), for coumarin 102 (C102)
      dissolved in a binary mixture of aniline and an inert solvent (cyclohexane or
      toluene). The PET induced fluorescence follows an anomalous trend against the
      mole fraction of aniline (XAN); first quenches up to certain XAN (0.075 for
      cyclohexane; 0.13 for toluene), thereafter, enhances with increase in XAN.
      Although the non-interacting component cannot directly participate in the PET
      process, it may modulate C102-aniline H-bonding association by changing the
      polarity of the medium or by disrupting the aniline-aniline H-bond. The study
      clearly illustrates the dominant role of hydrogen bonding in activating the
      electron transfer rate where standard thermodynamics predicts very weak donor
      acceptor interaction. 

PMID- 24562299
TI  - Combined therapies of antithrombotics and antioxidants delay in silico brain
      tumour progression.
AB  - Glioblastoma multiforme (GBM), the most frequent type of primary brain tumour, is
      a rapidly evolving and spatially heterogeneous high-grade astrocytoma that
      presents areas of necrosis, hypercellularity and microvascular hyperplasia. The
      aberrant vasculature leads to hypoxic areas and results in an increase in
      oxidative stress, selecting for more invasive tumour cell phenotypes. In our
      study, we assay in silico different therapeutic approaches which combine
      antithrombotics (ATs), antioxidants and standard radiotherapy (RT). To do so, we
      have developed a biocomputational model of GBM that incorporates the spatio
      temporal interplay among two glioma cell phenotypes corresponding to oxygenated
      and hypoxic cells, a necrotic core and the local vasculature whose response
      evolves with tumour progression. Our numerical simulations predict that suitable
      combinations of ATs and antioxidants may diminish, in a synergistic way,
      oxidative stress and the subsequent hypoxic response. This novel therapeutical
      strategy, with potentially low or no toxicity, might reduce tumour invasion and
      further sensitize GBM to conventional RT or other cytotoxic agents, hopefully
      increasing median patient overall survival time. 

PMID- 24562300
TI  - The combined evidential value of autosomal and Y-chromosomal DNA profiles
      obtained from the same sample.
AB  - When a Y-chromosomal and a (partial) autosomal DNA profile are obtained from one
      crime sample, and both profiles match the suspect's profiles, we would like to
      know the combined evidential value. To calculate the likelihood ratio of
      observing the autosomal and Y-chromosomal DNA profiles combined, we need to know
      the conditional random match probability of the observed autosomal DNA profile,
      given the Y-chromosomal match. We examine this conditional probability in two
      ways: (1) with a database containing data of 2,085 men and (2) using a simulation
      model. We conclude that if the Y-chromosomal DNA profiles match, we can still
      regard the autosomal DNA profile as independent from the Y-chromosomal DNA
      profile if the matching person is not a descendant of the father of the donor of
      the (crime) sample. The evidential value can, in that case, be computed by
      multiplying the random match probabilities of the individual profiles. 

PMID- 24562301
TI  - Magnetic fields and leukaemia risks in UK electricity supply workers.
AB  - AIMS: To investigate whether leukaemia risks are related to occupational exposure
      to low-frequency magnetic fields. METHODS: Leukaemia risks experienced by 73 051
      employees of the former Central Electricity Generating Board of England and Wales
      were investigated for the period 1973-2010. All employees were hired in the
      period 1952-82 and were employed for at least 6 months with some employment in
      the period 1973-82. Detailed calculations had been performed by others to enable
      an assessment to be made of exposures to magnetic fields. Poisson regression was
      used to calculate relative risks (rate ratios) of developing leukaemia or
      leukaemia subtypes for categories of lifetime, distant (lagged) and recent
      (lugged) exposure. RESULTS: Findings for all leukaemias combined were
      unexceptional; risks were close to unity for all exposure categories and there
      was no suggestion of risks increasing with cumulative (or recent or distant)
      magnetic field exposures. There were no statistically significant dose-response
      effects shown for acute myeloid leukaemia, chronic myeloid leukaemia or chronic
      lymphocytic leukaemia. There was a significant positive trend for acute
      lymphocytic leukaemia (ALL), but this was based, in the main, on unusually low
      risks in the lowest exposure category. CONCLUSIONS: This study found no
      convincing evidence to support the hypothesis that exposure to magnetic fields is
      a risk factor for leukaemia, and the findings are consistent with the hypotheses
      that both distant and recent magnetic field exposures are not causally related to
      the generality of leukaemia. The limited positive findings for ALL may well be
      chance findings.

PMID- 24562302
TI  - Magnetic fields and brain tumour risks in UK electricity supply workers.
AB  - AIMS: To investigate whether brain tumour risks are related to occupational
      exposure to low-frequency magnetic fields. METHODS: Brain tumour risks
      experienced by 73 051 employees of the former Central Electricity Generating
      Board of England and Wales were investigated for the period 1973-2010. All
      employees were hired in the period 1952-82 and were employed for at least 6
      months with some employment in the period 1973-82. Detailed calculations had been
      performed by others to enable an assessment to be made of exposures to magnetic
      fields. Poisson regression was used to calculate relative risks (rate ratios) of
      developing a brain tumour (or glioma or meningioma) for categories of lifetime,
      distant (lagged) and recent (lugged) exposure. RESULTS: Findings for glioma and
      for the generality of all brain tumours were unexceptional; risks were close to
      (or below) unity for all exposure categories and there was no suggestion of risks
      increasing with cumulative (or recent or distant) magnetic field exposures. There
      were no statistically significant dose-response effects shown for meningioma, but
      there was some evidence of elevated risks in the three highest exposure
      categories for exposures received >10 years ago. CONCLUSIONS: This study found no
      evidence to support the hypothesis that exposure to magnetic fields is a risk
      factor for gliomas, and the findings are consistent with the hypotheses that both
      distant and recent magnetic field exposures are not causally related to gliomas.
      The limited positive findings for meningioma may be chance findings; national
      comparisons argue against a causal interpretation.

PMID- 24562303
TI  - Examining paid sickness absence by shift workers.
AB  - BACKGROUND: Shift workers are at greater risk than day workers with respect to
      psychological and physical health, yet little research has linked shift work to
      increased sickness absence. AIMS: To investigate the relationship between shift
      work and sickness absence while controlling for organizational and individual
      characteristics and shift work attributes that have confounded previous research.
      METHODS: The study used archive data collected from three national surveys in
      Canada, each involving over 20000 employees and 6000 private-sector firms in 14
      different occupational groups. The employees reported the number of paid sickness
      absence days in the past 12 months. Data were analysed using both chi-squared
      statistics and hierarchical regressions. RESULTS: Contrary to previous research,
      shift workers took less paid sickness absence than day workers. There were no
      differences in the length of the sickness absence between both groups or in
      sickness absence taken by female and male workers whether working days or shifts.
      Only job tenure, the presence of a union in the workplace and working rotating
      shifts predicted sickness absence in shift workers. The results were consistent
      across all three samples. CONCLUSIONS: In general, shift work does not seem to be
      linked to increased sickness absence. However, such associations may be true for
      specific industries. Male and female workers did not differ in the amount of
      sickness absence taken. Rotating shifts, regardless of industry, predicted
      sickness absence among shift workers. Consideration should be given to
      implementing scheduled time off between shift changes.

PMID- 24562304
TI  - Prognostic biomarkers: an introduction.

PMID- 24562305
TI  - PPARalpha ligand clofibrate ameliorates blood pressure and vascular reactivity in
      spontaneously hypertensive rats.
AB  - AIM: Peroxisome proliferator activated receptors (PPARs) are nuclear
      transcription factors that regulate numerous genes influencing blood pressure.
      The aim of this study was to examine the effects of clofibrate, a PPARalpha
      ligand, on blood pressure in spontaneously hypertensive rats (SHR). METHODS:
      Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR), 8-9 weeks old, were
      randomly allocated into groups treated with vehicle or clofibrate (250 mg.kg(
      1).d(-1), ip for 21 d). Systolic blood pressure (SBP) was measured before and
      after the study period using tail-cuff plethysmography. Rats were sacrificed
      under anesthesia and blood, urine and tissue samples were processed for
      subsequent analysis. RESULTS: SHR rats showed significantly higher SBP compared
      with WKY rats (198+/-6 mmHg vs 93+/-7 mmHg), and a 3-fold increase in urinary
      protein excretion. Clofibrate treatment reduced SBP by 26%+/-2% and proteinuria
      by 43%+/-9% in SHR but not in WKY rats. The urinary nitrite/nitrate excretion in
      SHR rats was nearly 2-fold greater than that in WKY, and was further increased by
      30%+/-4% and 48%+/-3%, respectively, following clofibrate treatment. In addition,
      PPARalpha protein expression and PPARalpha activity were significantly lower in
      SHR than that in WKY rats. Clofibrate treatment significantly increased PPARalpha
      protein expression and PPARalpha activity in SHR rats, but not in WKY rats.
      Moreover, the vasoconstrictor response of aortic ring was markedly increased in
      SHRs, which was blunted after clofibrate treatment. CONCLUSION: PPARalpha
      contributes to regulation of blood pressure and vascular reactivity in SHR, and
      clofibrate-mediated reduction in blood pressure and proteinuria is probably
      through increased NO production.

PMID- 24562306
TI  - Docosahexaenoic acid inhibits melanin synthesis in murine melanoma cells in vitro
      through increasing tyrosinase degradation.
AB  - AIM: To investigate the effects of docosahexaenoic acid (DHA) on melanin
      synthesis and related regulatory mechanisms. METHODS: B16F10 mouse melanoma cells
      were exposed to DHA for 3 d, and melanin content and tyrosinase activity were
      measured. Western blot analysis was used to analyze the protein levels in DHA
      mediated signal transduction pathways. RESULTS: DHA (1-25 MUmol/L) did not affect
      the viability of B16F10 cells, but decreased alpha-MSH-induced melanin synthesis
      in a concentration-dependent manner. DHA concentration-dependently reduced
      tyrosinase activity in the cells, but did not affect mushroom tyrosinase activity
      in a cell-free system. Furthermore, DHA treatment significantly reduced
      tyrosinase level without affecting microphthalmia-associated transcription factor
      (MITF) in the cells. DHA did not activate ERK and Akt in the cells. Pretreatment
      with the proteasome inhibitor MG132 (80 nmol/L) abolished DHA-induced tyrosinase
      reduction. CONCLUSION: DHA inhibits melanogenesis in B16F10 cells in vitro
      through increasing tyrosinase degradation. The results suggest that DHA may be a
      potential agent for treatment of hyperpigmentary disorders of skin.

PMID- 24562307
TI  - Paeonol protects rat vascular endothelial cells from ox-LDL-induced injury in
      vitro via downregulating microRNA-21 expression and TNF-alpha release.
AB  - AIM: Paeonol (2'-hydroxy-4'-methoxyacetophenone) from Cortex moutan root is a
      potential therapeutic agent for atherosclerosis. This study sought to investigate
      the mechanisms underlying anti-inflammatory effects of paeonol in rat vascular
      endothelial cells (VECs) in vitro. METHODS: VECs were isolated from rat thoracic
      aortas. The cells were pretreated with paeonol for 24 h, and then stimulated with
      ox-LDL for another 24 h. The expression of microRNA-21 (miR-21) and PTEN in VECs
      was analyzed using qRT-PCR. The expression of PTEN protein was detected by
      Western blotting. TNF-alpha release by VECs was measured by ELISA. RESULTS: Ox
      LDL treatment inhibited VEC growth in dose- and time-dependent manners (the value
      of IC50 was about 20 mg/L at 24 h). Furthermore, ox-LDL (20 mg/L) significantly
      increased miR-21 expression and inhibited the expression of PTEN, one of
      downstream target genes of miR-21 in VECs. In addition, ox-LDL (20 mg/L)
      significantly increased the release of TNF-alpha from VECs. Pretreatment with
      paeonol increased the survival rate of ox-LDL-treated VECs in dose- and time
      dependent manners. Moreover, paeonol (120 MUmol/L) prevented ox-LDL-induced
      increases in miR-21 expression and TNF-alpha release, and ox-LDL-induced
      inhibition in PTEN expression. A dual-luciferase reporter assay showed that miR
      21 bound directly to PTEN's 3'-UTR, thus inhibiting PTEN expression. In ox-LDL
      treated VECs, transfection with a miR-21 mimic significantly increased miR-21
      expression and inhibited PTEN expression, and attenuated the protective effects
      of paeonol pretreatment, whereas transfection with an miR-21 inhibitor
      significantly decreased miR-21 expression and increased PTEN expression, thus
      enhanced the protective effects of paeonol pretreatment. CONCLUSION: miR-21 is an
      important target of paeonol for its protective effects against ox-LDL-induced VEC
      injury, which may play critical roles in development of atherosclerosis.

PMID- 24562308
TI  - Lactoferrin inhibits apoptosis through insulin-like growth factor I in primary
      rat osteoblasts.
AB  - AIM: Excessive apoptosis of osteoblasts is the major cause of low bone mass, and
      bovine lactoferrin (bLF), an iron-binding glycoprotein, might protect
      osteoblastic cells from apoptosis induced by serum withdrawal. The aim of this
      study was to elucidate the mechanisms underlying the anti-apoptotic action of bLF
      in rat osteoblasts in vitro. METHODS: Primary rat osteoblasts were incubated in
      the presence of varying concentrations of bLF for 24 h. The expression of insulin
      like growth factor I (IGF-I) and IGF-I receptor (IGF-IR) was measured uisng RT
      PCR and Western blotting. Cell apoptosis was examined with flow cytometry. siRNAs
      targeting IGF-I was used in this study. RESULTS: Treatment of bLF (0.1-1000
      MUg/mL) dose-dependently increased the expression of IGF-I and IGF-IR in the
      osteoblasts. Treatment with bLF (10, 100 MUg/mL) markedly inhibited the
      osteoblast apoptosis (with the rate of total apoptosis of 70% at 10 MUg/mL), but
      the high concentration of bLF (1000 MUg/mL) significantly promoted the osteoblast
      apoptosis. Knockdown of the IGF-I gene in osteoblasts with siRNA markedly
      increased the osteoblast apoptosis. CONCLUSION: Lactoferrin (10 and 100 MUg/mL)
      effectively inhibits apoptosis of primary rat osteoblasts by upregulating IGF-I
      expression.

PMID- 24562311
TI  - Photoluminescent AuCu bimetallic nanoclusters as pH sensors and catalysts.
AB  - A facile and one-pot approach to the preparation of gold (Au) and copper (Cu)
      bimetallic nanoclusters (NCs) is unveiled. AuCu NCs reveal features of orange
      photoluminescence (PL), reversible pH-dependent PL properties, and efficient
      catalytic activity for degradation of methylene blue (MB). 

PMID- 24562312
TI  - Non-covalent interactions of the carcinogen (+)-anti-BPDE with exon 1 of the
      human K-ras proto-oncogene.
AB  - Investigating the complementary, but different, effects of physical (non
      covalent) and chemical (covalent) mutagen-DNA and carcinogen-DNA interactions is
      important for understanding possible mechanisms of development and prevention of
      mutagenesis and carcinogenesis. A highly mutagenic and carcinogenic metabolite of
      the polycyclic aromatic hydrocarbon benzo[alpha]pyrene, namely (+)-anti-BPDE, is
      known to undergo both physical and chemical complexation with DNA. Previous
      studies of BPDE-DNA complex formation have focused on processes that require
      substantial structural reorganization, such as intercalation, and consequently
      relatively long time scales. However, some initial processes which occur within
      shorter time scales, such as external non-covalent binding, and which do not
      require major DNA structural reorganization have not been thoroughly
      investigated. A detailed computational study of such initial BPDE-DNA
      interactions is needed to elucidate the temporal and structural origins of the
      major covalent adduct, a promutagenic, which is known to exist in an external (+)
      trans-anti-BPDE-N(2)-dGuanosine configuration. Accordingly, the initial stages of
      external non-covalent BPDE-DNA binding are studied in this work as well as their
      relationship to subsequent formation of the major, also external, covalent
      adduct. To study mechanisms that occur prior to extensive DNA structural
      reorganization, we present a first and detailed codon by codon computational
      study of the non-covalent interactions of (+)-anti-BPDE with DNA. In particular,
      due to its relevance to carcinogenesis, the interaction of (+)-anti-BPDE with
      exon 1 of the human K-ras gene has been studied. External solvent-exposed non
      covalent binding sites have been found which may be precursors of the major
      external trans adduct and, importantly, are located in codons 12 and 13 of the K
      ras gene which are known to be key mutation hotspots. In addition, our study
      explains and correctly predicts preferential (+)-anti-BPDE binding at minor
      groove guanosines. A subtle combination of van der Waals and hydrogen bonding
      interactions has been found to be a primary factor in preferentially positioning
      (+)-anti-BPDE toward the 5' position of a guanosine's strand, consistent with
      proton NMR observations for the major trans adduct, and at 5'-TGG-3' sequences
      which are known to yield high binding probability. 

PMID- 24562309
TI  - Innate lymphoid cells integrate stromal and immunological signals to enhance
      antibody production by splenic marginal zone B cells.
AB  - Innate lymphoid cells (ILCs) regulate stromal cells, epithelial cells and cells
      of the immune system, but their effect on B cells remains unclear. Here we
      identified RORgammat(+) ILCs near the marginal zone (MZ), a splenic compartment
      that contains innate-like B cells highly responsive to circulating T cell
      independent (TI) antigens. Splenic ILCs established bidirectional crosstalk with
      MAdCAM-1(+) marginal reticular cells by providing tumor-necrosis factor (TNF) and
      lymphotoxin, and they stimulated MZ B cells via B cell-activation factor (BAFF),
      the ligand of the costimulatory receptor CD40 (CD40L) and the Notch ligand Delta
      like 1 (DLL1). Splenic ILCs further helped MZ B cells and their plasma-cell
      progeny by coopting neutrophils through release of the cytokine GM-CSF.
      Consequently, depletion of ILCs impaired both pre- and post-immune TI antibody
      responses. Thus, ILCs integrate stromal and myeloid signals to orchestrate innate
      like antibody production at the interface between the immune system and
      circulatory system. 

PMID- 24562310
TI  - TLR-driven early glycolytic reprogramming via the kinases TBK1-IKKE supports the
      anabolic demands of dendritic cell activation.
AB  - The ligation of Toll-like receptors (TLRs) leads to rapid activation of dendritic
      cells (DCs). However, the metabolic requirements that support this process remain
      poorly defined. We found that DC glycolytic flux increased within minutes of
      exposure to TLR agonists and that this served an essential role in supporting the
      de novo synthesis of fatty acids for the expansion of the endoplasmic reticulum
      and Golgi required for the production and secretion of proteins that are integral
      to DC activation. Signaling via the kinases TBK1, IKKE and Akt was essential for
      the TLR-induced increase in glycolysis by promoting the association of the
      glycolytic enzyme HK-II with mitochondria. In summary, we identified the rapid
      induction of glycolysis as an integral component of TLR signaling that is
      essential for the anabolic demands of the activation and function of DCs. 

PMID- 24562314
TI  - Fluoroscopy time during uncomplicated unilateral ureteroscopy for urolithiasis
      decreases with urology resident experience.
AB  - PURPOSE: To determine predictors of fluoroscopy time during uncomplicated,
      unilateral ureteroscopy for urolithiasis performed by urology residents during
      the first 2 years of residency. METHODS: The patient charts and computed
      tomography scans of consecutive, unilateral, uncomplicated ureteroscopy cases for
      urolithiasis were retrospectively reviewed. The cases were performed by beginning
      urology residents over the course of their first 2 years of urology residency
      training. RESULTS: A total of 200 ureteroscopy cases were reviewed. The mean
      stone diameter was 7.1 (+/-3.2) mm. Forty-three percent of cases were performed
      for renal stones and 58 % for ureteral stones. The mean operative time was 80.2
      (+/-36.9) min. The mean fluoroscopy time was 69.1 (+/-38.2) s. No significant
      differences existed between cases performed by each of the two residents, and no
      statistical differences in case difficulty were observed throughout the study
      period. Linear regression analysis revealed the strongest association with lower
      fluoroscopy time to be increasing resident experience (p < 0.001). By the end of
      the 2-year review, fluoroscopy time decreased by 79 % from 135 to 29 s per case.
      Other significant factors associated with increasing fluoroscopy time were
      placement of a postoperative stent under fluoroscopic guidance (p < 0.001),
      utilization of a flexible ureteroscope as opposed to a semirigid ureteroscope (p
      < 0.001), and balloon dilation of the ureteral orifice (p < 0.001). CONCLUSIONS:
      Fluoroscopy time during uncomplicated, unilateral ureteroscopy for urolithiasis
      decreases with increasing urology resident operative experience. Other technical
      options during ureteroscopy were also found to influence fluoroscopy time.

PMID- 24562313
TI  - Dentin matrix proteins (DMPs) enhance differentiation of BMMSCs via ERK and P38
      MAPK pathways.
AB  - Dentin, the predominant mineralized tissue of the tooth, comprises an
      extracellular matrix of collagen and a heterogeneous mixture of non-collagenous
      components, many of which have cellular signaling properties. These properties
      may be important in signaling stem cell involvement in tissue regeneration
      following injury and the present study investigates their morphogenic effects on
      differentiation of Bone Marrow Stromal Stem Cells (BMMSCs) in vitro. Non
      collagenous dentin matrix proteins (DMPs) were isolated from healthy human teeth
      and their effects on BMMSCs behavior examined during in vitro culture. In vitro,
      DMPs enhanced alkaline phosphatase activity and mineralization in BMMSCs cultures
      as well as increasing the expression of dentinogenic and osteogenic
      differentiation markers (including runt-related transcription factor 2, osterix,
      bone sialoprotein, dentin sialophosphoprotein and osteocalcin) at both transcript
      and protein levels, with 10 MUg/mL DMPs being the optimal stimulatory
      concentration. Expression of phosphor-ERK/phosphor-P38 in BMMSCs was up-regulated
      by DMPs and, in the presence of the ERK1/2- and p38-specific inhibitors, the
      differentiation of BMMSCs was inhibited. These data indicate that DMPs promote
      the dentinogenic/osteogenic differentiation of BMMSCs via the ERK/p38 MAPK
      pathways.

PMID- 24562315
TI  - Single-Incision Transumbilical Surgery (SITUS) versus Single-Port Laparoscopic
      Surgery and conventional laparoscopic surgery: a prospective randomized
      comparative study of performance with novices in a dry laboratory.
AB  - PURPOSE: To evaluate the Single-Incision Transumbilical Surgery (SITUS) technique
      as compared to an established laparoendoscopic single-site surgery (LESS)
      technique (Single-Port Laparoscopic Surgery, SPLS) and conventional laparoscopy
      (CLS) in a surgical simulator model. METHODS: Sixty-three medical students
      without previous laparoscopic experience were randomly assigned to one of the
      three groups (SITUS, SPLS and CLS). Subjects were asked to perform five
      standardized tasks of increasing difficulty adopted from the Fundamentals of
      Laparoscopic Surgery curriculum. Statistical evaluation included task completion
      times and accuracy. RESULTS: Overall performances of all tasks (except precision
      cutting) were significantly faster and of higher accuracy in the CLS and SITUS
      groups than in the SPLS group (p = 0.004 to p < 0.001). CLS and SITUS groups
      alone showed no significant difference in performance times and accuracy
      measurements for all tasks (p = 0.048 to p = 0.989). CONCLUSIONS: SITUS proved to
      be a simple, but highly effective technique to overcome restrictions of SPLS. In
      a surgical simulator model, novices were able to achieve task performances
      comparable to CLS and did significantly better than using a port-assisted LESS
      technique such as SPLS. The demonstrated advantages of SITUS may be attributed to
      a preservation of the basic principles of conventional laparoscopy, such as the
      use of straight instruments and an adequate degree of triangulation.

PMID- 24562316
TI  - Aurora A Kinase as a diagnostic urinary marker for urothelial bladder cancer.
AB  - OBJECTIVE: To evaluate urinary Aurora A Kinase (AURKA) mRNA expression as a
      diagnostic biomarker for urothelial bladder cancer (UBC). METHODS: One hundred
      and eighty-eight urine samples from patients with UBC (n = 122) and controls with
      hematuria (n = 66) were investigated. AURKA expression was quantified using real
      time PCR and compared with voided urinary cytology. Associations with stage and
      grade were assessed. The area under curve was used to quantify the predictive
      accuracy (PA). RESULTS: The sensitivity and the specificity of AURKA for UBC were
      83.6 and 65.2 %, respectively (PA = 74.4 %). Among those with detectable AURKA,
      the quantity of expression was similar in cases and controls. Compared with Ta,
      tumors staged T1 and T2 showed a 9.31-fold and 4.78-fold increased AURKA
      expression (p = 0.034), respectively. Further, high-grade tumors showed 5.33-fold
      higher expression levels than low-grade tumors (p = 0.031). AURKA and urinary
      cytology showed similar overall PA for UBC detection (74.4 vs. 72.1 %, p =
      0.588). For low-grade tumors, AURKA was more accurate (72.5 vs. 59.0 %, p =
      0.004), while cytology was more accurate for high-grade lesions (76.8 vs. 89.1 %,
      p = 0.011). CONCLUSIONS: In patients with hematuria, AURKA is associated with the
      presence and grade of UBC, suggesting a role as diagnostic and prognostic
      biomarker. As AURKA is more accurate in low-grade tumors but less accurate in
      high-grade tumors than urinary cytology, both could be complementary in detecting
      UBC.

PMID- 24562317
TI  - Parental bonding and suicidality in pregnant teenagers: a population-based study
      in southern Brazil.
AB  - PURPOSE: To assess the associations of the perceived quality of parental bonding
      with suicidality in a sample of pregnant adolescents. METHODS: A cross-sectional
      study with a sample size of 828 pregnant teenagers receiving prenatal medical
      assistance in the national public health system in the urban area of Pelotas,
      southern Brazil. Suicidality and psychiatric disorders were assessed using the
      Mini International Neuropsychiatric Interview (MINI), and the Parental Bonding
      Instrument (PBI) was employed to measure the perceived quality of parental
      bonding. A self-report questionnaire was used to collect sociodemographic,
      obstetric and other psychosocial data. RESULTS: Forty-three (4.94 %) teenagers
      from a consecutive sample of 871 refused to participate, resulting in 828
      participants. Prevalence of suicidality was 13.3 %, lifetime suicide attempts
      were 7.4 % with 1.3 % reporting attempting suicide within the last month.
      Significant associations of suicidality with the 18-19-year-old subgroup, low
      education, prior abortion, physical abuse within the last 12 months were present,
      and most psychiatric disorders were associated with a higher suicidality
      prevalence. Additionally, after adjustment in the multivariate analysis, the
      style of parental bonding was independently associated with suicidality in the
      pregnant adolescent, with a PR of 2.53 (95 % CI 1.14-5.59) for the maternal
      'affectionless control' and a PR of 2.91 (95 % CI 1.10-7.70) for the paternal
      'neglectful parenting.' CONCLUSIONS: We found that maternal 'affectionless
      control' and paternal 'neglectful parenting' were independent predictors of
      suicidality in this sample of pregnant teenagers.

PMID- 24562318
TI  - The prevalence of metabolic syndrome in people with severe mental illness: a
      mediation analysis.
AB  - BACKGROUND: People with severe mental illness (SMI) generally have high rates of
      metabolic syndrome (MetS). Proposed explanations remain conjectural. Relatively
      little is known about Mets in SMI in Southern Europe, an area with generally
      healthy dietary traditions. PURPOSE: To establish prevalence rates of MetS in an
      Italian sample, and testing hypotheses about putative reasons for the excess in
      the SMI group. METHODS: We compared the prevalence and correlates of MetS in
      inpatients with SMI and controls randomly chosen from patients undergoing routine
      maxillofacial surgery. We employed formal tests of mediation. RESULTS: The MetS
      prevalence rate was 26.1 % in the SMI group and 15.9 % in the comparison group.
      After controlling for age, people with SMI were three times more likely to have
      MetS than their non-SMI counterparts. Smoking and a family history of
      cardiovascular disease were strongly related to MetS in both groups. However,
      these factors could not explain the excess of MetS in the SMI group, and we found
      no effect of antipsychotic dose. CONCLUSIONS: SMI remained prominent in
      increasing the likelihood of MetS in this low prevalence population, and putative
      determinants of MetS were common to people with SMI and to controls. Explanations
      for high MetS rates in SMI may lie in health behaviours other than smoking.

PMID- 24562319
TI  - CTOs: what is the state of the evidence?
AB  - PURPOSE: Community Treatment Orders (CTOs) require outpatients to adhere to
      treatment and permit rapid hospitalisation when necessary. They have become a
      clinical and policy solution to repeated hospital readmissions despite some
      strong opposition and the contested nature of published evidence. In this
      article, we appraise the current literature on CTOs from the viewpoint of
      Evidence-Based Medicine and discuss the way forward for using and researching
      CTOs. RESULTS: Non-randomised outcome studies show conflicting results, but their
      lack of standardisation of methods and measures makes it difficult to draw
      conclusions. In contrast, all three randomised controlled trials (RCTs) conducted
      concur in their findings that CTOs do not impact on hospital outcomes. No
      systematic review or meta-analysis has identified any clear clinical advantage to
      CTOs. CONCLUSION: The evidence-base does not support the use of CTOs in their
      current form. Involuntary clinical interventions must conform to the highest
      standard of evidence-based care. To enable clinicians to take an evidence-based
      approach and to settle remaining uncertainties about the current evidence, high
      quality RCTs should be designed and undertaken, using standardised outcome
      measures.

PMID- 24562321
TI  - Complications of transplantation. Part 1: renal transplants.
AB  - Vascular complications after solid-organ transplantation are not uncommon and may
      lead to graft dysfunction and ultimately graft loss. A thorough understanding of
      the surgical anatomy, etiologies, and types of vascular complications, their
      presentation, and the options for management are important for managing these
      complex patients. This article reviews the basic surgical anatomy, vascular
      complications, and endovascular management options of vascular complications in
      patients with renal transplants. 

PMID- 24562322
TI  - Learning an Internal Dynamics Model from Control Demonstration.
AB  - Much work in optimal control and inverse control has assumed that the controller
      has perfect knowledge of plant dynamics. However, if the controller is a human or
      animal subject, the subject's internal dynamics model may differ from the true
      plant dynamics. Here, we consider the problem of learning the subject's internal
      model from demonstrations of control and knowledge of task goals. Due to sensory
      feedback delay, the subject uses an internal model to generate an internal
      prediction of the current plant state, which may differ from the actual plant
      state. We develop a probabilistic framework and exact EM algorithm to jointly
      estimate the internal model, internal state trajectories, and feedback delay. We
      applied this framework to demonstrations by a nonhuman primate of brain-machine
      interface (BMI) control. We discovered that the subject's internal model deviated
      from the true BMI plant dynamics and provided significantly better explanation of
      the recorded neural control signals than did the true plant dynamics.

PMID- 24562323
TI  - Room temperature biological quantum random walk in phycocyanin nanowires.
AB  - Quantum nano-structures are likely to become primary elements of future devices.
      However, there are a number of significant scientific challenges to real world
      applications of quantum devices. These include de-coherence that erodes operation
      of a quantum device and control issues. In nature, certain processes have been
      shown to use quantum mechanical processes for overcoming these barriers. One well
      known example is the high energy transmission efficiency of photosynthetic light
      harvesting complexes. Utilizing such systems for fabricating nano-devices
      provides a new approach to creating self-assembled nano-energy guides. In this
      study, we use isolated phycocyanin (PC) proteins that can self-assemble into
      bundles of nanowires. We show two methods for controlling the organization of the
      bundles. These nanowires exhibit long range quantum energy transfer through
      hundreds of proteins. Such results provide new efficient building blocks for
      coupling to nano-devices, and shed light on distribution and the efficiency of
      energy transfer mechanisms in biological systems and its quantum nature. 

PMID- 24562320
TI  - The interface of physical and mental health.
AB  - PURPOSE: The interaction between physical and mental health is complex. In this
      paper we aim to provide an overview of the main components of this relationship
      and to identify how care could be improved for people with co-morbidities.
      METHODS: We performed a literature search of MedLine, Ovid and Psycinfo and
      identified studies that examined the association between mental illness and
      physical illness. We also examined the key policy documents and guidelines in
      this area. RESULTS: People with mental health conditions are at higher risk of
      developing physical illness, have those conditions diagnosed later and have much
      higher mortality rates. Conversely, people with a diagnosis of physical illness,
      especially cardiovascular disease, diabetes and cancer have a greater chance of
      developing a mental health problem. When both mental and physical illnesses
      conditions are present together, there are higher overall rates of morbidity,
      healthcare utilisation, and poorer quality of life. CONCLUSIONS: Physicians and
      psychiatrists need to be aware of the co-occurrence of mental and physical health
      problems and the challenges posed for both general and mental health services.
      There is a need to screen appropriately in both settings to ensure timely
      diagnosis and treatment. Liaison psychiatry provides psychological assessment and
      treatment for people with physical illness, but there is a gap in the provision
      of physical healthcare for people with severe mental illness. There is a need for
      public policy to drive this forward to overcome the institutional barriers to
      equitable access to healthcare and for educators to reverse the tendency to teach
      mind and body as separate systems.

PMID- 24562324
TI  - Acanthamoeba release compounds which promote growth of Listeria monocytogenes and
      other bacteria.
AB  - Listeria monocytogenes can grow as a saphrophyte in diverse habitats, e.g., soil,
      rivers, lakes, and on decaying plant material. In these environments, the
      bacteria are frequently exposed to predatory protozoa such as Acanthamoeba.
      Although L. monocytogenes is a facultative intracellular pathogen it does not
      infect or survive intracellular in Acanthamoeba castellanii, unlike several other
      facultative intracellular bacteria. Instead, motile L. monocytogenes can form
      large aggregates on amoebal cells and are effectively phagocytosed and eventually
      digested by Acanthamoeba. Here, we demonstrate that non-motile L. monocytogenes
      represent a less preferred prey in co-cultures with A. castellanii. Moreover, we
      found that the presence of Acanthamoeba strongly promotes growth of the bacteria
      in non-nutrient saline, by releasing nutrients or other growth promoters. Thus,
      the lack of motility and ability to utilize amoebal metabolites may aid to avoid
      eradication by amoebal predation in low-nutrient environments.

PMID- 24562326
TI  - Properties and applications of undecylprodigiosin and other bacterial
      prodigiosins.
AB  - The growing demand to fulfill the needs of present-day medicine in terms of novel
      effective molecules has lead to reexamining some of the old and known bacterial
      secondary metabolites. Bacterial prodigiosins (prodiginines) have a long history
      of being re markable multipurpose compounds, best examined for their anticancer
      and antimalarial activities. Production of prodigiosin in the most common
      producer strain Serratia marcescens has been described in great detail. However,
      few reports have discussed the ecophysiological roles of these molecules in the
      producing strains, as well as their antibiotic and UV-protective properties. This
      review describes recent advances in the production process, biosynthesis,
      properties, and applications of bacterial prodigiosins. Special emphasis is put
      on undecylprodigiosin which has generally been a less studied member of the
      prodigiosin family. In addition, it has been suggested that proteins involved in
      undecylprodigiosin synthesis, RedG and RedH, could be a useful addition to the
      biocatalytic toolbox being able to mediate regio- and stereoselective oxidative
      cyclization. Judging by the number of recent references (216 for the 2007-2013
      period), it has become clear that undecylprodigiosin and other bacterial
      prodigiosins still hold surprises in terms of valuable properties and applicative
      potential to medical and other industrial fields and that they still deserve
      continuing research curiosity. 

PMID- 24562327
TI  - Two-step production of D-lactate from mixed sugars by growing and resting cells
      of metabolically engineered Lactobacillus plantarum.
AB  - To develop cost-effective systems for D-lactate production, here, the effect of
      high-cell density cultivation of metabolically engineered Lactobacillus plantarum
      on D-lactate production was evaluated. A xylose-assimilating strain of L.
      plantarum was anaerobically cultured with mixed sugars (glucose and xylose) as
      substrates. Compared to undiluted nutrient-rich de Man, Rogosa, and Sharpe (MRS)
      medium, D-lactate production by cultivating in 10-fold diluted MRS (0.1 MRS)
      medium or normal saline solution was 89.7 and 81.3 %, respectively. Notably, the
      xylose consumption rate was comparable in the three cultures, whereas the glucose
      consumption rate decreased by 18.3 and 26.1 % in 0.1 MRS medium and normal saline
      solution, respectively, resulting in a reduction of the D-lactate production
      rate. The D-lactate productivity in high-cell density cultivation was
      proportional to the initial cell concentrations. The use of a two-step
      cultivation process involving growing and resting cells in a single bioreactor
      revealed that the ratio of the glucose and xylose consumption rates (based on
      grams consumed) in resting cell conditions was 1.88, whereas that in growing
      conditions was 2.58. Cultivation of L. plantarum in growing conditions for 24 h
      produced 73.2 g/l D-lactate with the yield of 0.90 g/g, whereas cells cultivation
      under resting cell conditions in a saline solution for 24 h produced 68.7 g/l D
      lactate with the yield of 0.93 g/g. In total, 141.9 g/l D-lactate was produced
      after 48 h cultivation, a value that represents the highest reported
      concentration of D-lactate produced from mixed sugars to date. Our findings
      contribute to the cost-effective, large-scale production of D-lactate. 

PMID- 24562325
TI  - Antifungal and antiviral products of marine organisms.
AB  - Marine organisms including bacteria, fungi, algae, sponges, echinoderms,
      mollusks, and cephalochordates produce a variety of products with antifungal
      activity including bacterial chitinases, lipopeptides, and lactones; fungal (-)
      sclerotiorin and peptaibols, purpurides B and C, berkedrimane B and purpuride;
      algal gambieric acids A and B, phlorotannins; 3,5-dibromo-2-(3,5-dibromo-2
      methoxyphenoxy)phenol, spongistatin 1, eurysterols A and B, nortetillapyrone,
      bromotyrosine alkaloids, bis-indole alkaloid, ageloxime B and (-)-ageloxime D,
      haliscosamine, hamigeran G, hippolachnin A from sponges; echinoderm triterpene
      glycosides and alkene sulfates; molluscan kahalalide F and a 1485-Da peptide with
      a sequence SRSELIVHQR; and cepalochordate chitotriosidase and a 5026.9-Da
      antifungal peptide. The antiviral compounds from marine organisms include
      bacterial polysaccharide and furan-2-yl acetate; fungal macrolide, purpurester A,
      purpurquinone B, isoindolone derivatives, alterporriol Q, tetrahydroaltersolanol
      C and asperterrestide A, algal diterpenes, xylogalactofucan, alginic acid,
      glycolipid sulfoquinovosyldiacylglycerol, sulfated polysaccharide p-KG03,
      meroditerpenoids, methyl ester derivative of vatomaric acid, lectins,
      polysaccharides, tannins, cnidarian zoanthoxanthin alkaloids, norditerpenoid and
      capilloquinol; crustacean antilipopolysaccharide factors, molluscan hemocyanin;
      echinoderm triterpenoid glycosides; tunicate didemnin B, tamandarins A and B and;
      tilapia hepcidin 1-5 (TH 1-5), seabream SauMx1, SauMx2, and SauMx3, and orange
      spotted grouper beta-defensin. Although the mechanisms of antifungal and
      antiviral activities of only some of the aforementioned compounds have been
      elucidated, the possibility to use those known to have distinctly different
      mechanisms, good bioavailability, and minimal toxicity in combination therapy
      remains to be investigated. It is also worthwhile to test the marine
      antimicrobials for possible synergism with existing drugs. The prospects of
      employing them in clinical practice are promising in view of the wealth of these
      compounds from marine organisms. The compounds may also be used in agriculture
      and the food industry. 

PMID- 24562328
TI  - Lipidomic analysis of serum from high fat diet induced obese mice.
AB  - Lipid metabolites regulate fatty acid and glucose homeostasis. The intention of
      the current study is to identify circulating lipid species, which are altered in
      rodent obesity and strongly correlate with the classically measured metabolites
      glucose, triglycerides, and cholesterol. Mice fed a high fat diet (HFD) for 14
      weeks have increased body weight and fasting glucose. Serum triglycerides are not
      altered, while cholesterol tends to be increased. Accordingly, major cholesteryl
      ester (CE) species and free cholesterol are not significantly raised in obesity
      while minor metabolites, including CE 20:3 and CE 18:3, are increased or reduced,
      respectively. Distinct sphingomyelin (SM) species are elevated while ceramides
      are not raised. Phosphatidylinositol (PI) species, including PI 34:1, are raised
      while others are decreased. PI 34:1 strongly correlates with fasting glucose and
      proinsulin levels. Phosphatidylcholine (PC) 26:0, 40:2, and 40:5, which are
      induced in obesity, correlate with cholesterol. PC 38:4 and PC 40:6 are also
      raised in fat fed mice and positively correlate with fasting glucose.
      Lysophosphatidylcholine (LPC) species are also changed in obesity and the already
      shown reduction of LPC 16:1 has been confirmed. LPC 22:4, which is increased,
      correlates with serum cholesterol. The data indicate that circulating levels of
      various lipid species are changed in the obesity model studied and some of them
      are strongly associated with classically measured metabolites. 

PMID- 24562330
TI  - Barley beta-glucans-containing food enhances probiotic performances of beneficial
      bacteria.
AB  - Currently, the majority of prebiotics in the market are derived from non
      digestible oligosaccharides. Very few studies have focused on non-digestible long
      chain complex polysaccharides in relation to their potential as novel prebiotics.
      Cereals beta-glucans have been investigated for immune-modulating properties and
      beneficial effects on obesity, cardiovascular diseases, diabetes, and cholesterol
      levels. Moreover, beta-glucans have been reported to be highly fermentable by the
      intestinal microbiota in the caecum and colon, and can enhance both growth rate
      and lactic acid production of microbes isolated from the human intestine. In this
      work, we report the effects of food matrices containing barley beta-glucans on
      growth and probiotic features of four Lactobacillus strains. Such matrices were
      able to improve the growth rate of the tested bacteria both in unstressed
      conditions and, importantly, after exposure to in vitro simulation of the
      digestive tract. Moreover, the effect of beta-glucans-containing food on
      bacterial adhesion to enterocyte-like cells was analyzed and a positive influence
      on probiotic-enterocyte interaction was observed. 

PMID- 24562329
TI  - Recent progress in understanding subtype specific regulation of NMDA receptors by
      G Protein Coupled Receptors (GPCRs).
AB  - G Protein Coupled Receptors (GPCRs) are the largest family of receptors whose
      ligands constitute nearly a third of prescription drugs in the market. They are
      widely involved in diverse physiological functions including learning and memory.
      NMDA receptors (NMDARs), which belong to the ionotropic glutamate receptor
      family, are likewise ubiquitously expressed in the central nervous system (CNS)
      and play a pivotal role in learning and memory. Despite its critical contribution
      to physiological and pathophysiological processes, few pharmacological
      interventions aimed directly at regulating NMDAR function have been developed to
      date. However, it is well established that NMDAR function is precisely regulated
      by cellular signalling cascades recruited downstream of G protein coupled
      receptor (GPCR) stimulation. Accordingly, the downstream regulation of NMDARs
      likely represents an important determinant of outcome following treatment with
      neuropsychiatric agents that target selected GPCRs. Importantly, the functional
      consequence of such regulation on NMDAR function varies, based not only on the
      identity of the GPCR, but also on the cell type in which relevant receptors are
      expressed. Indeed, the mechanisms responsible for regulating NMDARs by GPCRs
      involve numerous intracellular signalling molecules and regulatory proteins that
      vary from one cell type to another. In the present article, we highlight recent
      findings from studies that have uncovered novel mechanisms by which selected
      GPCRs regulate NMDAR function and consequently NMDAR-dependent plasticity. 

PMID- 24562331
TI  - Differential effects of high-fish oil and high-lard diets on cells and cytokines
      involved in the inflammatory process in rat insulin-sensitive tissues.
AB  - Dietary fat sources may differentially affect the development of inflammation in
      insulin-sensitive tissues during chronic overfeeding. Considering the anti
      inflammatory properties of omega-3 fatty acids, this study aimed to compare the
      effects of chronic high-fish oil and high-lard diets on obesity-related
      inflammation by evaluating serum and tissue adipokine levels and histological
      features in insulin-sensitive tissues (white adipose tissue, skeletal muscle and
      liver). As expected, a high-lard diet induced systemic and peripheral
      inflammation and insulin resistance. Conversely, compared with a high-lard diet,
      a high-fish oil diet resulted in a lower degree of systemic inflammation and
      insulin resistance that were associated with a lower adipocyte diameter as well
      as lower immunoreactivity for transforming growth factor beta 1 (TGFbeta1) in
      white adipose tissue. A high-fish oil diet also resulted in a lower ectopic lipid
      depot, inflammation degree and insulin resistance in the skeletal muscle and
      liver. Moreover, a high-fish oil diet attenuated hepatic stellate cell activation
      and fibrogenesis in the liver, as indicated by the smooth muscle alpha-actin
      (alpha-SMA) and TGFbeta1 levels. The replacement of lard (saturated fatty acids)
      with fish oil (omega-3 fatty acids) in chronic high-fat feeding attenuated the
      development of systemic and tissue inflammation. 

PMID- 24562332
TI  - Large-scale domain motions and pyridoxal-5'-phosphate assisted radical catalysis
      in coenzyme B12-dependent aminomutases.
AB  - Lysine 5,6-aminomutase (5,6-LAM) and ornithine 4,5-aminomutase (4,5-OAM) are two
      of the rare enzymes that use assistance of two vitamins as cofactors. These
      enzymes employ radical generating capability of coenzyme B12 (5'
      deoxyadenosylcobalamin, dAdoCbl) and ability of pyridoxal-5'-phosphate (PLP,
      vitamin B6) to stabilize high-energy intermediates for performing challenging 1,2
      amino rearrangements between adjacent carbons. A large-scale domain movement is
      required for interconversion between the catalytically inactive open form and the
      catalytically active closed form. In spite of all the similarities, these enzymes
      differ in substrate specificities. 4,5-OAM is highly specific for D-ornithine as
      a substrate while 5,6-LAM can accept D-lysine and L-beta-lysine. This review
      focuses on recent computational, spectroscopic and structural studies of these
      enzymes and their implications on the related enzymes. Additionally, we also
      discuss the potential biosynthetic application of 5,6-LAM. 

PMID- 24562333
TI  - Nanostructured guidance for peripheral nerve injuries: a review with a
      perspective in the oral and maxillofacial area.
AB  - Injury to peripheral nerves can occur as a result of various surgical procedures,
      including oral and maxillofacial surgery. In the case of nerve transaction, the
      gold standard treatment is the end-to-end reconnection of the two nerve stumps.
      When it cannot be performed, the actual strategies consist of the positioning of
      a nerve graft between the two stumps. Guided nerve regeneration using nano
      structured scaffolds is a promising strategy to promote axon regeneration.
      Biodegradable electrospun conduits composed of aligned nanofibers is a new class
      of devices used to improve neurite extension and axon outgrowth. Self assembled
      peptide nanofibrous scaffolds (SAPNSs) demonstrated promising results in animal
      models for central nervous system injuries, and, more recently, for peripheral
      nerve injury. Aims of this work are (1) to review electrospun and self-assembled
      nanofibrous scaffolds use in vitro and in vivo for peripheral nerve regeneration;
      and (2) its application in peripheral nerve injuries treatment. The review
      focused on nanofibrous scaffolds with a diameter of less than approximately 250
      nm. The conjugation in a nano scale of a natural bioactive factor with a
      resorbable synthetic or natural material may represent the best compromise
      providing both biological and mechanical cues for guided nerve regeneration.
      Injured peripheral nerves, such as trigeminal and facial, may benefit from these
      treatments. 

PMID- 24562335
TI  - Non-dipping and arterial hypertension depend on clinical factors rather than on
      genetic variability of ACE and RGS2 genes in patients with type 1 diabetes.
AB  - The aim of our study was to characterize the association of clinical and genetic
      risk factors such as: ACE genotype (rs17997552, rs1800764, rs4459609) and RGS2
      (rs2746071) with the development of hypertension (HT) and non-dipping phenomenon
      in patients with type 1 diabetes mellitus (T1DM). A total of 238 adolescents and
      young adults with T1DM-103 females and 135 males, aged 8-30 years (mean 17.35 +/-
      5.2) with diabetes duration 1-26 years (mean 7.72 +/- 6.2), with mean HbA1c
      (IFCC) 58 +/- 15 mmol/mmol-were subjected to 24-h ambulatory blood pressure
      measurements (ABPM). The results of the ABPM were analyzed in association with
      the polymorphisms of ACE and RGS2 genes and clinical data of patients. HT was
      recognized in 65 (27 %) and non-dipping in 111 (46.63 %) patients. In the
      multivariate analysis of factors predisposing to HT, the variables that remained
      significant were the following: male sex (OR 1.62; 95 % CI 1.171-2.250), non
      dipping (OR 1.40; 95 % CI 1.03-1.90) and total cholesterol level (OR 1.01; 95 %
      CI 1.005-1.021). The only factor influencing non-dipping was the duration of
      diabetes-OR 1.09 (95 % CI 1.04-1.14). The patients displaying non-dipping have a
      twice increased risk of development of HT (OR 2.17; 95 % CI 1.21-3.89). There was
      no association between disturbances of blood pressure (BP) and genotypes of ACE:
      rs17997552, rs1800764, rs4459609 and RGS2: rs2746071. Clinical rather than
      genetic risk factors seem to be connected with BP disturbances in young patients
      with T1DM. Although we have identified representative groups of HT versus non-HT
      and dipping versus non-dipping subjects, the effect of genetic predisposition to
      the development of higher BP is too weak to be statistically significant. 

PMID- 24562334
TI  - Genetics of oxidative stress in obesity.
AB  - Obesity is a multifactorial disease characterized by the excessive accumulation
      of fat in adipose tissue and peripheral organs. Its derived metabolic
      complications are mediated by the associated oxidative stress, inflammation and
      hypoxia. Oxidative stress is due to the excessive production of reactive oxygen
      species or diminished antioxidant defenses. Genetic variants, such as single
      nucleotide polymorphisms in antioxidant defense system genes, could alter the
      efficacy of these enzymes and, ultimately, the risk of obesity; thus, studies
      investigating the role of genetic variations in genes related to oxidative stress
      could be useful for better understanding the etiology of obesity and its
      metabolic complications. The lack of existing literature reviews in this field
      encouraged us to gather the findings from studies focusing on the impact of
      single nucleotide polymorphisms in antioxidant enzymes, oxidative stress
      producing systems and transcription factor genes concerning their association
      with obesity risk and its phenotypes. In the future, the characterization of
      these single nucleotide polymorphisms (SNPs) in obese patients could contribute
      to the development of controlled antioxidant therapies potentially beneficial for
      the treatment of obesity-derived metabolic complications. 

PMID- 24562348
TI  - The amino terminus extension in the long dipeptidyl peptidase 9 isoform contains
      a nuclear localization signal targeting the active peptidase to the nucleus.
AB  - The intracellular prolyl peptidase DPP9 is implied to be involved in various
      cellular pathways including amino acid recycling, antigen maturation, cellular
      homeostasis, and viability. Interestingly, the major RNA transcript of DPP9
      contains two possible translation initiation sites, which could potentially
      generate a longer (892 aa) and a shorter version (863 aa) of DPP9. Although the
      endogenous expression of the shorter DPP9 form has been previously verified, it
      is unknown whether the longer version is expressed, and what is its biological
      significance. By developing specific antibodies against the amino-terminal
      extension of the putative DPP9-long form, we demonstrate for the first time the
      endogenous expression of this longer isoform within cells. Furthermore, we show
      that DPP9-long represents a significant fraction of total DPP9 in cells, under
      steady-state conditions. Using biochemical cell fractionation assays in
      combination with immunofluorescence studies, we find the two isoforms localize to
      separate subcellular compartments. Whereas DPP9-short is present in the cytosol,
      DPP9-long localizes preferentially to the nucleus. This differential localization
      is attributed to a classical monopartite nuclear localization signal
      (K(K/R)X(K/R)) in the N-terminal extension of DPP9-long. Furthermore, we detect
      prolyl peptidase activity in nuclear fractions, which can be inhibited by
      specific DPP8/9 inhibitors. In conclusion, a considerable fraction of DPP9, which
      was previously considered as a purely cytosolic peptidase, localizes to the
      nucleus and is active there, raising the intriguing possibility that the longer
      DPP9 isoform may regulate the activity or stability of nuclear proteins, such as
      transcription factors. 

PMID- 24562347
TI  - Role of microRNAs in malignant mesothelioma.
AB  - Malignant mesothelioma (MM) is an aggressive tumor, mainly derived from the
      pleura, which is predominantly associated with exposure to asbestos fibers. The
      prognosis of MM patients is particularly severe, with a median survival of
      approximately 9-12 months and latency between exposure and diagnosis ranging from
      20-50 years (median 30 years). Emerging evidence has demonstrated that tumor
      aggressiveness is associated with genome and gene expression abnormalities;
      therefore, several studies have recently focused on the role of microRNAs
      (miRNAs) in MM tumorigenesis. miRNAs are small non-protein coding single-stranded
      RNAs (17-22 nucleotides) involved in numerous cellular processes that negatively
      regulate gene expression by modulating the expression of downstream target genes.
      miRNAs are often deregulated in cancer; in particular, the differential miRNA
      expression profiles of MM cells compared to unaffected mesothelial cells have
      suggested potential roles of miRNAs as either oncogenes or tumor suppressor genes
      in MM oncogenesis. In this review, the mechanism of MM carcinogenesis was
      evaluated through the analysis of the published miRNA expression data. The roles
      of miRNAs as diagnostic biomarkers and prognostic factors for potential
      therapeutic strategies will be presented and discussed.

PMID- 24562350
TI  - Scaling up intensified tuberculosis case finding in HIV clinics in Rwanda.
AB  - BACKGROUND: Tuberculosis (TB) is the leading cause of morbidity and mortality
      among people living with HIV (PLHIV) in sub-Saharan Africa. Early TB detection
      and treatment is key to saving lives of PLHIV. Rwanda began implementing
      intensified TB case finding (ICF) in 2005 in line with World Health Organization
      policy on TB/HIV collaborative activities. We aimed to describe trends of ICF in
      PLHIV newly enrolled into HIV clinics. METHODS: We used routinely collected
      program data on ICF from facility-based pre-antiretroviral therapy/antiretroviral
      therapy registers in Rwandan HIV clinics from 2006 to 2011. Semiannual, active
      data collection for PLHIV newly enrolled into HIV care included proportion
      screened for TB, proportion screened positive, and percentage with active TB and
      started anti-TB drugs. RESULTS: The number of health facilities reporting TB
      screening indicators increased 16-fold, from 20 facilities in the first semester
      of 2006 to 328 facilities by the end of 2011. The proportion of patients screened
      increased progressively from 77% of newly enrolled patients in first semester of
      2006 to 94% at the end of 2011 (P < 0.001). The proportion of patients who
      screened positive decreased over time, from 23% in the first semester of 2006 to
      10% at the end of 2011 (P < 0.001). The proportion of active TB cases remained
      relatively constant over time at 2.2%. CONCLUSIONS: Rwanda has increased the
      proportion of newly enrolled PLHIV screened for TB using a simple screening
      protocol. Countries with limited resources but high HIV and TB disease prevalence
      should implement ICF as part of their integrated HIV-TB treatment programs.

PMID- 24562349
TI  - Cardiovascular disease risk factors in HIV-infected women after initiation of
      lopinavir/ritonavir- and nevirapine-based antiretroviral therapy in Sub-Saharan
      Africa: A5208 (OCTANE).
AB  - BACKGROUND: Limited comparative, prospective data exist regarding cardiovascular
      risk factors in HIV-infected women starting antiretroviral therapy in Africa.
      METHODS: In 7 African countries, 741 women with CD4 <200 cells/mm were randomized
      to tenofovir/emtricitabine (TDF/FTC) plus either nevirapine (NVP, n = 370) or
      lopinavir/ritonavir (LPV/r, n = 371). Lipids and blood pressure (BP) were
      evaluated at entry, 48, 96, and 144 weeks. Multivariable linear and logistic
      regression models were used to evaluate mean risk factor changes and clinically
      relevant risk factor changes. RESULTS: At entry, both NVP and LPV/r groups were
      similar regarding age [mean = 33.5 (SD = 7.1) years], CD4 [129 (67) cells/mm],
      and HIV-1 RNA [5.1 (0.6) log10 copies/mL]. Nearly, all women had normal lipids
      and BP except for high-density lipoprotein (HDL)-cholesterol. Over 144 weeks, the
      LPV/r compared with NVP group had significantly greater mean lipid increases (eg,
      non-HDL: +29 vs. +13 mg/dL) and smaller HDL increases (+12 vs. +21 mg/dL). In
      contrast, the NVP compared with LPV/r group had greater mean increases in BP (eg,
      diastolic BP: +5 vs. -0.5 mm Hg). Significantly, more women assigned LPV/r had
      week 144 "abnormal" lipid levels (eg, HDL 29.7% vs. 14.8% and triglycerides 28.6%
      vs. 8.2%), and significantly, more women assigned NVP had "abnormal" BP (eg,
      diastolic BP 22.7% vs. 6.5%). Most differences remained significant when adjusted
      for baseline risk factor, age, CD4, and HIV-1 RNA. CONCLUSIONS: In HIV-infected
      women initiating antiretroviral therapy in Africa, LPV/r + TDF/FTC was associated
      with less favorable changes in lipids, and use of NVP + TDF/FTC was associated
      with less favorable changes in BP.

PMID- 24562373
TI  - Manipulating the excitation transfer in Photosystem I using a Fabry-Perot metal
      resonator with optical subwavelength dimensions.
AB  - We demonstrate controlled modification of the fluorescence and energy transfer
      properties of Photosystem I (PSI) - one of the most important light harvesting
      systems - by using a newly developed approach to produce optical subwavelength
      microcavities for cryogenic temperature issues. The experiments were carried out
      on PSI from the cyanobacterium Arthrospira platensis as it shows a broad and
      structured fluorescence emission. By changing the distance between the cavity
      forming mirrors, the electromagnetic field mode structure around PSI is varied
      affecting the emission and energy transfer properties, which allows us to
      selectively enhance signals of resonant emitters and suppress off-resonant
      emission. By comparing the experimental data with simulations, we are able to
      show how excitation transfer within PSI is affected by the microcavity. The
      ability to control the energy transfer within such efficient energy converters as
      photosynthetic proteins can establish the opportunity for enhancing the
      efficiencies of bio-solar applications. The defined control of the resonance
      conditions by microcavities makes them a preferable tool to study the effects of
      additional electromagnetic modes on the energy transfer in any coupled multi
      chromophore system. The resonator geometry excludes the direct contact of the
      proteins with any surface. Possible quenching or denaturation of the complexes
      close to metal surfaces is still an insuperable obstacle for studies with
      proteins and nanostructures, which can be avoided by resonators. 

PMID- 24562374
TI  - Carbon fiber/Co9S8 nanotube arrays hybrid structures for flexible quantum dot
      sensitized solar cells.
AB  - Recently, hybrid carbon materials and inorganic nanocrystals have received an
      intensive amount of attention and have opened up an exciting new field in the
      design and fabrication of high-performance catalysts. Here we present a novel
      kind of hybrid counter electrode (CE) consisting of a carbon fiber (CF) and Co9S8
      nanotube arrays (NTs) for fiber-shaped flexible quantum dot-sensitized solar
      cells (QDSSCs). The growth mechanisms of Co(CO3)0.35Cl0.20(OH)1.10 nanowire
      arrays (NWs) on the CFs were discussed, and the catalytic activity of the CF, Pt
      and Co9S8/CF hybrid structure (Co9S8@CF) were elucidated systematically as well.
      An absolute energy conversion efficiency of 3.79% has been demonstrated under 100
      mW cm(-2) AM 1.5 illumination by using Co9S8@CF as a CE. This work not only
      demonstrates an innovative approach for growing cobalt sulfide NTs on flexible
      substrates that can be applied in flexible devices for energy harvesting and
      storage, but also provides a kind of hybrid structure and high-efficiency CE for
      QDSSCs. 

PMID- 24562375
TI  - Factors affecting the implementation of clinical pharmacy services in China.
AB  - New policies in China have recently led to the implementation of clinical
      pharmacy services in hospitals. We explored the views of hospital administrators,
      pharmacy directors, clinical pharmacists, and dispensing pharmacists about the
      factors affecting clinical pharmacy services in China, using the framework
      approach and organizational theory. We conducted 30 interviews with 130
      participants at 29 hospitals (both secondary and tertiary) in Beijing, Zhengzhou,
      Luoyang, and Shanghai. We found that the barriers to and facilitators of
      implementation of clinical pharmacy services slotted into the environment and
      participant dimensions of Scott's adapted version of Leavitt's organizational
      model. External support from government was perceived as crucial to promoting
      pharmacy services. It is proposed that the internationally recognized Basel
      Statements of the International Pharmaceutical Federation also provide a strong
      foundation for guiding China in implementing clinical pharmacy services. 

PMID- 24562372
TI  - Individual differences in regional prefrontal gray matter morphometry and
      fractional anisotropy are associated with different constructs of executive
      function.
AB  - Although the relationship between structural differences within the prefrontal
      cortex (PFC) and executive function (EF) has been widely explored in cognitively
      impaired populations, little is known about this relationship in healthy young
      adults. Using optimized voxel-based morphometry (VBM), surface-based morphometry
      (SBM), and fractional anisotropy (FA) we determined the association between
      regional PFC grey matter (GM) morphometry and white matter tract diffusivity with
      performance on tasks that tap different aspects of EF as drawn from Miyake et
      al.'s three-factor model of EF. Reductions in both GM volume (VBM) and cortical
      folding (SBM) in the ventromedial PFC (vmPFC), ventrolateral PFC (vlPFC), and
      dorsolateral PFC (dlPFC) predicted better common EF, shifting-specific, and
      updating-specific performance, respectively. Despite capturing different
      components of GM morphometry, voxel- and surface-based findings were highly
      related, exhibiting regionally overlapping relationships with EF. Increased white
      matter FA in fiber tracts that connect the vmPFC and vlPFC with posterior regions
      of the brain also predicted better common EF and shifting-specific performance,
      respectively. These results suggest that the neural mechanisms supporting
      distinct aspects of EF may differentially rely on distinct regions of the PFC,
      and at least in healthy young adults, are influenced by regional morphometry of
      the PFC and the FA of major white matter tracts that connect the PFC with
      posterior cortical and subcortical regions. 

PMID- 24562376
TI  - In vitro differentiation of adipose-tissue-derived mesenchymal stem cells into
      neural retinal cells through expression of human PAX6 (5a) gene.
AB  - The neural retina is subjected to various degenerative conditions. Regenerative
      stem-cell-based therapy holds great promise for treating severe retinal
      degeneration diseases, although many drawbacks remain to be overcome. One
      important problem is to gain authentically differentiated cells for replacement.
      Paired box 6 protein (5a) (PAX6 (5a)) is a highly conserved master control gene
      that has an essential role in the development of the vertebrate visual system.
      Human adipose-tissue-derived stem cell (hADSC) isolation was performed by using
      fat tissues and was confirmed by the differentiation potential of the cells into
      adipocytes and osteocytes and by their surface marker profile. The coding region
      of the human PAX6 (5a) gene isoform was cloned and lentiviral particles were
      propagated in HEK293T. The differentiation of hADSCs into retinal cells was
      characterized by morphological characteristics, quantitative real-time reverse
      transcription plus the polymerase chain reaction (qPCR) and immunocytochemistry
      (ICC) for some retinal cell-specific and retinal pigmented epithelial (RPE) cell
      specific markers. hADSCs were successfully isolated. Flow cytometric analysis of
      surface markers indicated the high purity (~97 %) of isolated hADSCs. After 30 h
      of post-transduction, cells gradually showed the characteristic morphology of
      neuronal cells and small axon-like processes emerged. qPCR and ICC confirmed the
      differentiation of some neural retinal cells and RPE cells. Thus, PAX6 (5a)
      transcription factor expression, together with medium supplemented with
      fibronectin, is able to induce the differentiation of hADSCs into retinal
      progenitors, RPE cells and photoreceptors.

PMID- 24562377
TI  - Leukocyte recruitment in inflammation: basic concepts and new mechanistic
      insights based on new models and microscopic imaging technologies.
AB  - The immune cell system is a critical component of host defense. Recruitment of
      immune cells to sites of infection, immune reaction, or injury is complex and
      involves coordinated adhesive interactions between the leukocyte and the
      endothelial cell monolayer that lines blood vessels. This article reviews basic
      mechanisms in the recruitment of leukocytes to tissues and then selectively
      reviews new concepts that are emerging based on advances in live cell imaging
      microscopy and mouse strains. These emerging concepts are altering the
      conventional paradigms of inflammatory leukocyte recruitment established in the
      early 1990s. Indeed, recent publications have identified previously unrecognized
      contributions from pericytes and interstitial leukocytes and their secreted
      products that guide leukocytes to their targets. Investigators have also begun to
      design organs on a chip. Recent reports indicate that this avenue of research
      holds much promise. 

PMID- 24562380
TI  - Limitations of travel data for rate computations.

PMID- 24562381
TI  - Dopamine mediates vagal modulation of the immune system by electroacupuncture.
AB  - Previous anti-inflammatory strategies against sepsis, a leading cause of death in
      hospitals, had limited efficacy in clinical trials, in part because they targeted
      single cytokines and the experimental models failed to mimic clinical settings.
      Neuronal networks represent physiological mechanisms, selected by evolution to
      control inflammation, that can be exploited for the treatment of inflammatory and
      infectious disorders. Here, we report that sciatic nerve activation with
      electroacupuncture controls systemic inflammation and rescues mice from
      polymicrobial peritonitis. Electroacupuncture at the sciatic nerve controls
      systemic inflammation by inducing vagal activation of aromatic L-amino acid
      decarboxylase, leading to the production of dopamine in the adrenal medulla.
      Experimental models with adrenolectomized mice mimic clinical adrenal
      insufficiency, increase the susceptibility to sepsis and prevent the anti
      inflammatory effects of electroacupuncture. Dopamine inhibits cytokine production
      via dopamine type 1 (D1) receptors. D1 receptor agonists suppress systemic
      inflammation and rescue mice with adrenal insufficiency from polymicrobial
      peritonitis. Our results suggest a new anti-inflammatory mechanism mediated by
      the sciatic and vagus nerves that modulates the production of catecholamines in
      the adrenal glands. From a pharmacological perspective, the effects of selective
      dopamine agonists mimic the anti-inflammatory effects of electroacupuncture and
      can provide therapeutic advantages to control inflammation in infectious and
      inflammatory disorders. 

PMID- 24562384
TI  - Vorinostat in combination with lenalidomide and dexamethasone in patients with
      relapsed or refractory multiple myeloma.
AB  - The addition of vorinostat to lenalidomide/dexamethasone represents a novel
      combination therapy in multiple myeloma (MM), informed by laboratory studies
      suggesting synergy. This was a phase I, multicenter, open-label, non-randomized,
      dose-escalating study in patients with relapsed or relapsed and refractory MM.
      Clinical evaluation, electrocardiogram, laboratory studies and adverse events
      were obtained and assessed. The maximum-tolerated dose was not reached owing to a
      non-occurrence of two dose-limiting toxicities per six patients tested at any of
      the dosing levels. Patients tolerated the highest dose tested (Level 5) and this
      was considered the maximum administered dose: at 400 mg vorinostat on days 1-7
      and 15-21, 25 mg lenalidomide on days 1-21 and 40 mg dexamethasone on days 1, 8,
      15 and 22, per 28-day cycle. Drug-related adverse events were reported in 90% of
      patients serious adverse experiences were reported in 45% of the patients and 22%
      of all patients had adverse experiences considered, possibly related to study
      drug by the investigators. A confirmed partial response or better was reported
      for 14/30 patients (47%) evaluable for efficacy, including 31% of patients
      previously treated with lenalidomide. Vorinostat in combination with lenalidomide
      and dexamethasone proved tolerable with appropriate supportive care, with
      encouraging activity observed. 

PMID- 24562382
TI  - In vivo imaging using fluorescent antibodies to tumor necrosis factor predicts
      therapeutic response in Crohn's disease.
AB  - As antibodies to tumor necrosis factor (TNF) suppress immune responses in Crohn's
      disease by binding to membrane-bound TNF (mTNF), we created a fluorescent
      antibody for molecular mTNF imaging in this disease. Topical antibody
      administration in 25 patients with Crohn's disease led to detection of intestinal
      mTNF(+) immune cells during confocal laser endomicroscopy. Patients with high
      numbers of mTNF(+) cells showed significantly higher short-term response rates
      (92%) at week 12 upon subsequent anti-TNF therapy as compared to patients with
      low amounts of mTNF(+) cells (15%). This clinical response in the former patients
      was sustained over a follow-up period of 1 year and was associated with mucosal
      healing observed in follow-up endoscopy. These data indicate that molecular
      imaging with fluorescent antibodies has the potential to predict therapeutic
      responses to biological treatment and can be used for personalized medicine in
      Crohn's disease and autoimmune or inflammatory disorders. 

PMID- 24562385
TI  - Mutated calreticulin retains structurally disordered C terminus that cannot bind
      Ca(2+): some mechanistic and therapeutic implications.

PMID- 24562383
TI  - ARID1B is a specific vulnerability in ARID1A-mutant cancers.
AB  - Recent studies have revealed that ARID1A, encoding AT-rich interactive domain 1A
      (SWI-like), is frequently mutated across a variety of human cancers and also has
      bona fide tumor suppressor properties. Consequently, identification of
      vulnerabilities conferred by ARID1A mutation would have major relevance for human
      cancer. Here, using a broad screening approach, we identify ARID1B, an ARID1A
      homolog whose gene product is mutually exclusive with ARID1A in SWI/SNF
      complexes, as the number 1 gene preferentially required for the survival of
      ARID1A-mutant cancer cell lines. We show that loss of ARID1B in ARID1A-deficient
      backgrounds destabilizes SWI/SNF and impairs proliferation in both cancer cells
      and primary cells. We also find that ARID1A and ARID1B are frequently co-mutated
      in cancer but that ARID1A-deficient cancers retain at least one functional ARID1B
      allele. These results suggest that loss of ARID1A and ARID1B alleles
      cooperatively promotes cancer formation but also results in a unique functional
      dependence. The results further identify ARID1B as a potential therapeutic target
      for ARID1A-mutant cancers. 

PMID- 24562387
TI  - Sex hormone drives blood stem cell reproduction.
AB  - Stem cells ensure the maintenance of tissue homeostasis throughout life by
      tightly regulating their self-renewal and differentiation. In a recent study
      published in Nature, Nakada et al, 2014 unveil an unexpected endocrine mechanism
      that regulates hematopoietic stem cell (HSC) self-renewal. 

PMID- 24562386
TI  - A combination of Wnt and growth factor signaling induces Arl4c expression to form
      epithelial tubular structures.
AB  - Growth factor-dependent epithelial morphological changes and proliferation are
      essential for the formation of tubular structures, but the underlying molecular
      mechanisms are poorly understood. Co-stimulation with Wnt3a and epidermal growth
      factor (Wnt3a/EGF) induced development of tubes consisting of intestinal
      epithelial cells by inducing expression of Arl4c, an Arf-like small GTP-binding
      protein, in three-dimensional culture, while stimulation with Wnt3a or EGF alone
      did not. Arl4c expression resulted in rearrangement of the cytoskeleton through
      activation of Rac and inactivation of Rho properly, which promoted cell growth by
      inducing nuclear translocation of Yes-associated protein and transcriptional co
      activator with PDZ-binding motif (YAP/TAZ) in leading cells. Arl4c was expressed
      in ureteric bud tips and pretubular structures in the embryonic kidney. In an
      organoid culture assay, Wnt and fibroblast growth factor signaling simultaneously
      induced elongation and budding of kidney ureteric buds through Arl4c expression.
      YAP/TAZ was observed in the nucleus of extending ureteric bud tips. Thus, Arl4c
      expression induced by a combination of growth factor signaling mechanisms is
      involved in tube formation. 

PMID- 24562388
TI  - Modelling the co-occurrence of psychosis-like experiences and childhood sexual
      abuse.
AB  - PURPOSE: Recurrent research evidence indicates that childhood sexual abuse (CSA)
      is associated with psychosis and psychosis-like experiences (PLEs). Many
      individuals however who have experienced psychosis have never been sexually
      abused in childhood and many individuals who have experienced CSA have never
      experienced psychosis. METHOD: The current study sought to model the co
      occurrence of CSA and PLEs using data from the Adult Psychiatric Morbidity
      Survey. Latent class analysis was employed to identify distinct classes of
      individuals in the general population who were characterised by the presence, co
      occurrence or absence of PLEs and/or CSA. Multinomial logistic regression
      analysis was utilised to validate membership of classes characterised by both CSA
      and PLEs using a series of variables that have been proposed to delineate the co
      occurrence of these phenomena. RESULTS: Four hypothesised classes were
      identified, (1) a CSA-PLE co-occurrence class, (2) a PLE-only class, (3) a CSA
      only class and (4) a CSA and PLE free baseline class. CSA-PLE co-occurrence was
      characterised by neurotic disorder, social isolation, adult sexual molestation
      and a history of post-traumatic stress disorder (PTSD). PLE occurrence in the
      absence of CSA was characterised by neurotic disorder, social isolation, a
      history of PTSD, childhood physical abuse, and uniquely by discrimination and non
      sexual trauma post-16 years. CONCLUSIONS: The findings indicated that a distinct
      group of individuals in the population was characterised by the co-occurrence of
      CSA and PLEs. In the absence of CSA, individuals who experienced PLEs were likely
      to endure a wide range of other, non-sexual, traumatic and adverse experiences.
      The CSA-PLE co-occurrence class and its associated psychosocial risk profile was
      discussed in relation to established trauma-based perspectives of psychosis and
      PLEs.

PMID- 24562390
TI  - Two non-exclusive strategies employed to protect Torulopsis glabrata against
      hyperosmotic stress.
AB  - Several recent reports described an apoptosis-like programmed cell death (PCD)
      process in yeast in response to different environmental challenges. In this
      study, hyperosmotic stress caused by high NaCl concentration in culture medium
      induced cell death in the haploid yeast Torulopsis glabrata. Propidium iodide
      (PI) and PI/rhodamine-123 (Rh123) dual staining with flow cytometry showed that
      high salinity decreased intact cells by 16.5 %, increased necrotic cells by
      nearly twofold, and altered fermentative parameters appreciably. Morphological
      and biochemical indicators of apoptosis were apparent, specifically a decrease in
      mitochondrial membrane potential (?Psim), translocation of phosphatidylserine
      (PS) from the inner to the outer side of the plasma membrane, generation of
      reactive oxygen species (ROS), and involvement of caspase all while plasma
      membrane integrity was maintained. Additionally, it was found that overexpression
      of YCA1 drastically stimulated cell death, indicating that activation of
      metacaspase might lead to cell death. However, T. glabrata growth under
      hyperosmotic stress was enhanced when FIS1, HOG1, and GPD2 were overexpressed, or
      when exogenous proline or glutathione (GSH) were added into the cultures, both of
      which could repress caspase-3 activity. Thus, in these concrete cases of
      overexpression of anti-apoptotic or anti-necrotic factors and pharmacological
      manipulations, it decreased T. glabrata cell death that might help to achieve
      higher fermentative efficiency.

PMID- 24562389
TI  - Trend in rates for deaths with mention of schizophrenia on death certificates of
      US residents, 1999-2010.
AB  - BACKGROUND: Trends in mortality rates for schizophrenia using multiple causes of
      death (including contributory causes) coded on death certificates in the US
      resident population apparently have not been reported. METHODS: Age-standardized
      rates for deaths per 100,000 in 1999-2010 at age 15+ years (and for 15-64 and 65+
      years) with mention of schizophrenia were examined for the US resident
      population, including variation by age, gender, race (blacks/African Americans
      and whites) and region. RESULTS: Deaths at age 15+ years coded with schizophrenia
      as underlying cause were only 12 % of all deaths with mention of schizophrenia,
      for which the rate declined from 1.58 in 1999 (3,407 deaths) to 1.32 in 2010
      (3,422 deaths) (percentage change or PC = -16 %). Declines were larger in females
      than males, in whites than blacks, and occurred in the Northeast, Midwest and
      South but not the West. The rate increased for age 15-64 years (PC = +28 %)
      (mainly in males), however, while declining for age 65+ years (PC = -35 %). For
      deaths at age 15-64 years with schizophrenia coded as other than the underlying
      cause, the largest continuous increase was for endocrine-metabolic diseases
      (predominantly diabetes mellitus) as underlying cause, with smaller increases in
      males for cardiovascular diseases, external causes and neoplasms. CONCLUSION:
      Trends in the US rate for deaths with mention of schizophrenia varied among the
      sociodemographic groups examined. The lack of decline for age 15-64 years
      requires further study especially with regard to mediators (e.g., obesity) of
      excess mortality in schizophrenia identified from cohort studies.

PMID- 24562391
TI  - Reactivity of [K3(phen)8][Cu(NPh2)2]3--a possible intermediate in the copper(I)
      catalyzed N-arylation of N-phenylaniline.
AB  - Complex [K3(phen)8][Cu(NPh2)2]3 (1, phen = phenanthroline) was isolated from the
      catalytic C-N cross coupling reaction based on the CuI-phen-tBuOK catalytic
      system. Complex 1 can react with 4-iodotoluene to give 4-methyl-N,N
      diphenylaniline (3a) in 50% yield (based on all available NPh2(-) ligands of
      complex 1). In addition, 1 can also work as an effective catalyst for the C-N
      coupling reactions under the same reaction conditions, indicating that 1 may be
      an effective intermediate of the catalytic system. In the presence of 2,2,6,6
      tetramethylpiperidine-1-oxyl (TEMPO), a radical scavenger, the stoichiometric
      reaction between complex 1 and 4-iodotoluene was significantly quenched to give a
      low yield of 12%. The results suggest that the radical path dominates in the
      reaction, with (phen)KNPh2 as the possible radical source. The structures of 1
      and (phen)KNPh2 were both determined by single crystal X-ray diffraction studies.

PMID- 24562392
TI  - The Nd:YAG LIMAX(r) 120 high-output laser: local effects and resection capacity
      on liver parenchyma.
AB  - Various technical options are available for the resection of liver metastases,
      including CUSA, Ultracision, water-jet, and stapler devices. It has been shown
      that new generation high-output lasers are suitable for the resection of lung
      metastases. The goal of the present study was to evaluate the local effects of
      laser application on liver parenchyma. Livers of freshly slaughtered pigs (N = 6)
      were analyzed. The handheld laser was vertically held in the clamp of a hydraulic
      machine and sharply focused on the liver surface. The diode pumped Nd:YAG laser
      LIMAX(r) 120 (Gebruder Martin GmbH & Co. KG, Tuttlingen, Germany) moved evenly
      over the liver surface at speeds of 5, 10, and 20 mm/s. Laser outputs of 60 and
      120 W were applied at every speed. Histological sections (hematoxylin and eosin
      (HE) staining) of the extension area of vaporization and coagulation were
      analyzed by the use of the ImageJ software. In addition, the area of the liver
      parenchyma cut by the laser within 1 min was measured. The vaporized zone
      appeared wedge-shaped after histological section, whereas the area of coagulation
      appeared radiated outward. At 10 mm/s and 60 W, the mean vaporization of the
      measured zone was 356.6 +/- 3.9 MUm in length. Superficial coagulation was
      observed at 20 mm/s laser speed, without effective resection. At 120 W and 5 mm/s
      working speed, the mean vaporization zone and the average width of coagulation
      were largest with 664.6 +/- 5.9 and 375.6 +/- 2.3 MUm, respectively. The laser
      output power of 120 W allowed resection of an area of 6 +/- 0.4 cm(2) of liver
      parenchyma within 1 min. The Nd:YAG Laser LIMAX(r) 120 might be an effective tool
      for liver parenchyma dissection when it is applied at maximum output (120 W) and
      at a constant working speed of 5 mm/s.

PMID- 24562393
TI  - Mode of action of diterpene and characterization of related metabolites from the
      soft coral, Xenia elongata.
AB  - Chemical and biological investigation of the cultured marine soft coral Xenia
      elongata led to the isolation of two new diterpenes (2, 3). Their structures were
      elucidated using a combination of NMR and mass spectrometry. Biological
      evaluations and assessments were determined using the specific apoptosis
      induction assay based on genetically engineered mammalian cell line D3 deficient
      in Bak and Bax and derived from a mouse epithelial cell. The diterpenes induce
      apoptosis in low micromolar concentrations. The results indicate that the
      previously isolated compound (1) affects cell in a manner similar to that of
      HSP90 and HDAC inhibitors and in a manner opposite of PI3 kinase/mTOR inhibitors.
      Compound (3) inhibits selectively HDAC6 in high micromolar concentrations. 

PMID- 24562400
TI  - Utilization of evidence-based smoking cessation treatments by psychiatric
      inpatient smokers with depression.
AB  - OBJECTIVES: Although smoking is a major health issue among depressed psychiatric
      inpatients and interest in quitting is high, successful quit rates remain low
      among this population. We sought to understand preferences that depressed
      inpatient smokers may have for cessation treatments. METHODS: Eighty smokers (60%
      women, mean age 38.75 +/- 11.20) with major depressive disorder and nicotine
      dependence receiving psychiatric inpatient services provided information on
      current depressive symptoms, smoking status and nicotine dependence, quit
      attempts, perceived barriers to quitting, and smoking consequences. RESULTS:
      Almost half (46%) of participants endorsed a past-year quit attempt. Emotional
      barriers to quitting were uniquely associated with fewer past-year quit attempts,
      and depression severity was related to greater emotional barriers to quitting.
      Nicotine dependence severity was related to a variety of emotional, financial,
      weight concern, and self-efficacy barriers, but only weight gain concern was
      associated with decreased odds of making a past-year quit attempt. The number of
      lifetime quit attempts was positively associated with negative smoking
      consequences. With regard to interest in smoking cessation treatment, 86% and 92%
      of smokers reported a willingness to try behavioral counseling and nicotine
      replacement products, respectively, but fewer smokers reported a willingness to
      try medication, print or Web-based materials, or an unaided quit attempt.
      CONCLUSIONS: Although half of our sample reported recent quit attempts, many
      people did not make an attempt using an evidence-based treatment. On the basis of
      consumer preferences identified herein, clinical recommendations for reinforcing
      the use of evidence-based smoking cessation treatments for depressed psychiatric
      inpatient smokers are provided.

PMID- 24562401
TI  - Observational study on medications prescribed to dual-diagnosis outpatients.
AB  - OBJECTIVES: To quantify the number of medications used for treating psychiatric
      and addictive disorders in a cohort of dual diagnosis with substance dependence
      outpatients and report the most frequent pharmacological groups used. METHODS: A
      descriptive, cross-sectional study was conducted. Demographic data, Axis I
      comorbidity diagnosis with substance dependence, and the medications prescribed
      were recorded. Diagnosis was assessed by the Structured Clinical Interview for
      DSM-IV (SCID). RESULTS: One hundred seven patients (mean age 37.7 years; SD =
      10.2 years) were evaluated (76.6% men). On average, patients took 4.0 (SD = 1.8)
      medications. The pharmacological groups prescribed were antipsychotics (69.2%)
      followed by antidepressants (65.4%), antiepileptics (58.9%), anxiolytics (37.4%),
      alcohol-aversive drugs (15.9%), methadone (15.9%), lithium (3.7%), and naltrexone
      (2.8%). Older patients (>45 years old) were found to have a higher number of
      prescribed medications. Patients diagnosed with a dual psychotic disorder were
      prescribed a larger number of pharmacological agents (mean = 4.4; SD = 2.1) than
      patients with a mood disorder (mean = 3.7; SD = 1.3) or an anxiety disorder (mean
      = 2.9; SD = 1.2), K = 10.5, P = 0.005. CONCLUSIONS: Because polypharmacy is
      frequent in patients with mental illness and a co-occurring substance use
      disorder, specialized approaches need to be developed.

PMID- 24562402
TI  - Evaluation of an electronic medical record system at an opioid agonist treatment
      program.
AB  - OBJECTIVES: The Addiction Research and Treatment Corporation evaluated the impact
      of an electronic medical record system. METHODS: A prospective pre- and
      postimplementation design was utilized that examined the domains of quality,
      productivity, satisfaction, risk management, and financial performance. RESULTS:
      There were highly statistically significant improvements in timely completion of
      Annual Medical and 30-Day, 90-Day, and Annual Multidiscipline assessments. There
      was no statistically significant change in obtaining hepatitis C viral load for
      hepatitis C antibody-positive patients. The prevalence of risk management events
      was too low to detect statistically meaningful changes. Patient satisfaction was
      unchanged pre- and postimplementation, although staff satisfaction trended upward
      postimplementation. Productivity significantly declined for counseling staff;
      there was a nonsignificant productivity decline for medical services staff and a
      nonsignificant productivity increase for case manager staff. Revenue per capita
      staff increased by 0.6%, while cost per patient visit increased by 5.7%.
      CONCLUSIONS: Despite less robust results than expected, had we not implemented
      the electronic system, recent changes in documentation and reimbursement for
      services would have paralyzed our agency.

PMID- 24562407
TI  - The subtype CD200-positive, chorionic mesenchymal stem cells from the placenta
      promote regeneration of human hepatocytes.
AB  - Human placental mesenchymal stem cells (hPMSCs), for the treatment of fulminant
      hepatic failure, have been widely studied. Only a few studies have investigated
      the effect of the subtype CD200(+)hPMSCs on regeneration of human hepatocytes.
      CD200(+)hPMSCs can down-regulate activity of several immunocytes and suppress TNF
      alpha secretion from macrophages via the CD200-CD200R axis. We have investigated
      the influence of CD200-positive human placenta chorionic mesenchymal stem cells
      (CD200(+)hPCMSCs) on metabolism, proliferation and apoptosis of human hepatocytes
      in vitro. CD200(+)hPCMSCs promote urea synthesis, albumin secretion and
      hepatocytes proliferation at co-culture ratios of 1:1 and 3:1. Additionally,
      CD200(+)hPCMSCs inhibit hepatocyte apoptosis via up-regulation of an anti
      apoptotic protein, Bcl-xL. Thus, CD200(+)hPCMSCs can provide supportive benefit
      for the regeneration of human hepatocytes and also have immunosuppressive
      properties. Therefore, CD200(+)hPCMSCs may be an ideal candidate for stem cell
      based therapy in hepatic failure. 

PMID- 24562404
TI  - The effects of 1 Hz rTMS preconditioned by tDCS on gait kinematics in Parkinson's
      disease.
AB  - Hypokinetic gait is a common and very disabling symptom of Parkinson's disease
      (PD). Repetitive transcranial magnetic stimulation (rTMS) over the motor cortex
      has been used with variable effectiveness to treat hypokinesia in PD.
      Preconditioning rTMS by transcranial direct current stimulation (tDCS) may
      enhance its effectiveness to treat hypokinetic gait in PD. Three-dimensional
      kinematic gait analysis was performed (1) prior to, (2) immediately after and (3)
      30 min after low-frequency rTMS (1 Hz, 900 pulses, 80% of resting motor
      threshold) over M1 contralateral to the more affected body side preconditioned by
      (1) cathodal, (2) anodal or (3) sham tDCS (amperage: 1 mA, duration: 10 min) in
      ten subjects with PD (7 females, mean age 63 +/- 9 years) and ten healthy
      subjects (four females, mean age 50 +/- 11 years). The effects of tDCS
      preconditioned rTMS on gait kinematics were assessed by the following parameters:
      number of steps, step length, stride length, double support time, cadence, swing
      and stance phases. Our data suggest a bilateral improvement of hypokinetic gait
      in PD after 1 Hz rTMS over M1 of the more affected body side preceded by anodal
      tDCS. In contrast, 1 Hz rTMS alone (preceded by sham tDCS) and 1 Hz rTMS preceded
      by cathodal tDCS were ineffective to improve gait kinematics in PD. In healthy
      subjects, gait kinematics was unaffected by either intervention. Preconditioning
      motor cortex rTMS by tDCS is a promising approach to treat hypokinetic gait in
      PD.

PMID- 24562408
TI  - Enzyme-etching technique to fabricate micropatterns of aligned collagen fibrils.
AB  - A technique to tailor-make pre-coated, pre-aligned bovine collagen fibrils,
      derived from neonatal cardiomyocytes, on the surface of a glass slide into a
      designated pattern is reported. The unwanted collagen-coated area was erased by a
      collagenase solution and the tailored area was retained by attaching a
      microfabricated polydimethylsiloxane stamp directly to the collagen-coated
      surface. Using this technique, collagen patterns with designated orientations and
      with clear pattern boundaries and defined shapes were fabricated. 

PMID- 24562409
TI  - Hand position-dependent modulation of errors in vibrotactile temporal order
      judgments: the effects of transcranial magnetic stimulation to the human
      posterior parietal cortex.
AB  - The ability to decide which of the two stimuli is presented first can be probed
      using a temporal order judgment (TOJ) task. When the stimuli are delivered to the
      fingers, TOJ decisions can be confounded by the fact that the hands can be moved
      to different locations in space. How and where this confounded information is
      processed in the brain is poorly understood. In the present set of experiments,
      we addressed this knowledge gap by using single-pulse transcranial magnetic
      stimulation (TMS) to disrupt processing in the right or left posterior parietal
      cortex (PPC) during a vibrotactile TOJ task with stimuli applied to the right and
      left index fingers. In the first experiment, participants held their hands in an
      uncrossed configuration, and we found that when the index finger contralateral to
      the site of TMS was stimulated first, there was a significant increase in TOJ
      errors. This increase did not occur when stimuli were delivered to the
      ipsilateral finger first. In the second experiment, participants held their hands
      in a crossed configuration and the pattern of errors was reversed relative to the
      first experiment. In both the first two experiments, significant increases in TOJ
      error were present with TMS over either hemisphere, regardless of arm
      configuration; however, they were larger overall following TMS over the right
      PPC. Control experiments using sham TMS indicated the systematic modulation in
      error was not due to nonspecific effects of the stimulation. Additionally, we
      showed that these TMS-induced changes in TOJ errors were not due to a reduced
      ability to detect the timing of the vibrotactile stimuli. Taken together, these
      results demonstrate that both the right and left PPC contribute to the processing
      underlying vibrotactile TOJs by integrating vibrotactile information and
      proprioceptive information related to arm position in space. 

PMID- 24562403
TI  - The role of glutamate and its receptors in the proliferation, migration,
      differentiation and survival of neural progenitor cells.
AB  - The mammalian central nervous system derives from multipotent neural progenitor
      cells (NPCs) of the developing brain. During development the progenitor cells
      have enormous potential. They proliferate actively and differentiate into all the
      three main cell types, i.e., neurons, astrocytes and oligodendrocytes, of the
      adult brain through a tightly regulated process that coordinates cell
      proliferation, survival, migration, differentiation and apoptosis. This process
      is regulated by multiple extracellular signals including neurotrophic factors,
      chemoattractants and neurotransmitters in a coordinated manner. The main
      excitatory neurotransmitter glutamate is involved in promoting and/or inhibiting
      the proliferation, survival, migration and differentiation of NPCs acting via
      ionotropic or metabotropic receptors. The role of glutamate in the regulation of
      cortical NPCs has been most extensively studied. Glutamate appears to have a
      similar role in hippocampal, striatal as well as adult neural progenitors.
      Ionotropic alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid
      (AMPA)/kainate (KA) receptors and metabotropic glutamate receptor 5 (mGluR5) are
      expressed early during embryonic development as well as in the neurogenic zones
      of the adult brain. Ca(2+)-permeable AMPA/KA receptors are initially of
      importance for cell proliferation and neuronal motility. At later stages of
      development N-methyl-D-aspartate (NMDA) receptors have a more prominent role.
      MGluR5, which is the main metabotropic glutamate receptor during early
      development, is expressed in early progenitors and radial glial cells. Activation
      of this receptor promotes the proliferation and survival of NPCs. MGluR5 is
      involved in the extension of radial glial processes and in regulation of the
      migration of early cortical neurons. 

PMID- 24562410
TI  - Strategies used by individuals with multiple sclerosis and with mild disability
      to maintain dynamic stability during a steering task.
AB  - Changing direction during walking is a common task humans encounter every day.
      This destabilizing event requires the central nervous system (CNS) to quickly
      produce an appropriate response, maintain stability, and propel the body in the
      intended direction. Previous research has demonstrated that 'individuals with
      multiple sclerosis' (IwMS) with mild balance impairment display differences in
      gait characteristics during clinical tests compared with controls. The current
      study used dynamic stability margin [DSM, difference between COM (i.e. the
      weighted average of the central point of an individual's total body mass) and
      lateral BOS (i.e. the most lateral border of the foot that is in contact with the
      ground)] calculations in addition to gait kinematics to determine whether dynamic
      stability differences during a steering task were present between IwMS with mild
      balance impairment and 'healthy age-matched individuals' (HAMI) as well as
      between IwMS with mild balance impairment and 'community-dwelling older adults'
      (OA). All IwMS reported mild balance impairment with expanded disability status
      scale scores ranging between 1.0 and 3.0. The steering task required participants
      to walk 3 m towards a pressure sensitive trigger mat that would illuminate one of
      five lights to indicate the future direction of travel (i.e. straight, 45 degrees
      or 60 degrees  to the left or right of the midline). Results revealed that IwMS
      displayed reduced walking speed and cadence during the approach phase in addition
      to a smaller DSM range (i.e. COM remained close to lateral BOS) during the entire
      steering task when compared with HAMI. However, when compared to OAs, IwMS did
      not display differences in any of the gait kinematics or DSM calculations.
      Findings suggest that the IwMS displayed a conservative gait strategy in order to
      maintain stability during the steering task. Lack of dynamic stability
      differences between IwMS and OAs indicate that both groups use similar strategies
      to adapt locomotion as a result of impaired somatosensory quality and/or
      processing.

PMID- 24562412
TI  - Choroidal thickness is affected by many factors which may change the effect of
      ranibizumab: author's response.

PMID- 24562413
TI  - Three-dimensional metal/oxide nanocone arrays for high-performance
      electrochemical pseudocapacitors.
AB  - Three-dimensional (3D) electrodes are critical for enabling high-performance
      power sources. We report here on the design and fabrication, by combining imprint
      and soft-printing technologies, of 3D nanocone arrays as a novel platform for
      high performance pseudocapacitors. Such purpose-built 3D nanocone arrays have the
      advantages of simplicity/versatility/reliability of fabrication, generality to a
      vast range of active materials, high electrode surface area, and ease of
      electrolyte permeation. As a demonstration of principle, Au and MnO2 were
      sequentially deposited forming a 3D Au/MnOx nanocone array electrode for a
      pseudocapacitor device. This device achieved a specific mass (areal) capacitance
      of 840.3 F g(-1) (88.2 mF cm(-2)) at a current density of 2 A g(-1).
      Additionally, the asymmetric supercapacitor using the Au/MnOx nanocone array as
      the positive electrode and a carbon-based material as the negative electrode
      achieved a capacitance of 108.5 F g(-1) at a current density of 1 A g(-1),
      corresponding to an energy density of as high as 46.8 W h kg(-1) at a power
      density of 0.72 kW kg(-1). The cell still preserved 96.5% of the initial
      capacitance even after 2000 cycles at a current density of 2 A g(-1). The initial
      result is at least on a par with those of the best asymmetric supercapacitors
      reported so far, and thus bolsters the development value of the conductive
      nanocone arrays for high-performance supercapacitors and other energy-storage
      devices. 

PMID- 24562411
TI  - Unilateral imagined movement increases interhemispheric inhibition from the
      contralateral to ipsilateral motor cortex.
AB  - Whether a cortical drive to one limb modulates interhemispheric inhibition (IHI)
      from the active targeting to the non-active motor cortex (M1) remained unclear.
      The present study using a conditioning-test transcranial magnetic stimulation
      (TMS) paradigm aimed to directly demonstrate the modulation of IHI during
      unilateral voluntary or imagined movement in humans. Subjects were asked to
      actually perform right index-finger abduction (10-70% of the maximum voluntary
      contraction) or to imagine the movement. Conditioning and test TMS with an
      interstimulus interval of 5, 10, and 15 ms were applied over the left and right
      M1, respectively, and the test motor evoked potential (MEP) was recorded from the
      left first dorsal interosseous (FDI) muscle. The conditioning TMS intensity was
      adjusted ranging from 0.6 to 1.4 (in 0.2 steps) times the resting motor threshold
      (rMT). With test TMS alone, MEP in the left FDI muscle significantly increased
      during voluntary or imagined movement of the right index-finger. MEP amplitude
      was significantly reduced in proportion to increments of the conditioning TMS
      intensity at rest (1.2 and 1.4 times the rMT, P < 0.05, respectively).
      Importantly, the MEP inhibition was markedly enhanced during voluntary or
      imagined movement in comparison with that at rest. The regression analysis
      revealed that IHI varied depending on the intensity of the impulses conveyed from
      left to right M1, but not on the corticospinal excitability of the active right
      hand. Our results suggest that IHI from the active to non-active M1 is enhanced
      during unilateral volitional motor activity.

PMID- 24562414
TI  - Distinct and simultaneously active plasticity mechanisms in mouse hippocampus
      during different phases of Morris water maze training.
AB  - Although the Morris water maze (MWM) is the most frequently used protocol to
      examine hippocampus-dependent learning in mice, not much is known about the
      spatio-temporal dynamics of underlying plasticity processes. Here, we studied
      molecular and cellular hippocampal plasticity mechanisms during early and late
      phases of spatial learning in the MWM. Quantitative in situ hybridization for the
      immediate early genes zif268 and Homer1a (H1a) revealed phase-dependent
      differences in their expression between areas CA1 and CA3. During the initial
      learning phase, CA1 expression levels of the molecular plasticity marker H1a, but
      not of the activity reporter gene zif268, were related to task proficiency;
      whereas no learning-specific changes could be detected in CA3. Simultaneously,
      the ratio of surface-expressed NMDAR subunits NR2A and NR2B was downregulated as
      measured by acute slice biotinylation assay, while the total number of surface
      NMDARs was unaltered. When intrinsic 'somatic' and synaptic plasticity in the CA1
      region of hippocampal slices were examined, we found that early learning promotes
      intrinsic neuronal plasticity as manifested by a reduction of spike frequency
      adaptation and postburst afterhyperpolarization. At the synaptic level, however,
      maintenance of long-term potentiation (LTP) in all learning groups was impaired
      which is most likely due to 'intrinsic' learning-induced LTP which occluded any
      further electrically induced LTP. Late learning, in contrast, was characterized
      by re-normalized H1a, NR2A and NR2B expression and neuronal firing, yet a further
      strengthening of learning-induced LTP. Together, our data support a precisely
      timed cascade of complex molecular and subcellular transformations occurring from
      early to late MWM learning. 

PMID- 24562415
TI  - Interspecific and geographical variations of trace metal concentrations in
      cephalopods from Tunisian waters.
AB  - The concentrations of six metals (Ag, Cd, Cu, Hg, Pb, and Zn) were investigated
      and compared in three tissues (arms, digestive gland, and mantle) of three
      cephalopod species from the Tunisian waters: the common octopus (Octopus
      vulgaris), the common cuttlefish (Sepia officinalis), and the European squid
      (Loligo vulgaris). Whatever the species or the sites, the digestive gland
      displayed the highest concentrations of Ag, Cd, Cu, Pb, and Zn, highlighting its
      major role in their bioaccumulation and detoxification. This is also true for Hg
      but only for the digestive gland of O. vulgaris. Muscle from the arms and the
      mantle contained thus relatively low trace metal concentrations except for Hg in
      L. vulgaris and S. officinalis. Geographic comparison of metal concentrations in
      Tunisian cephalopods from three locations indicates that higher concentrations of
      Ag, Pb, and Hg were observed in cephalopods from northern and eastern coasts,
      whereas the highest Cd levels were detected in the southeastern, reflecting
      different conditions of exposure. Comparing the trace element concentrations
      between species, Ag, Cd, Cu, Hg, and Zn concentrations were the highest in the
      digestive gland of octopuses. This may be related to the differences in
      ecological features and swimming behavior among different cephalopod species.
      Effects of length and sex on metal levels were also considered, indicating a
      limited influence of sex on metal concentration.

PMID- 24562416
TI  - Diffusional correlations among multiple active sites in a single enzyme.
AB  - Simulations of the enzymatic dynamics of a model enzyme containing multiple
      substrate binding sites indicate the existence of diffusional correlations in the
      chemical reactivity of the active sites. A coarse-grain, particle-based,
      mesoscopic description of the system, comprising the enzyme, the substrate, the
      product and solvent, is constructed to study these effects. The reactive and non
      reactive dynamics is followed using a hybrid scheme that combines molecular
      dynamics for the enzyme, substrate and product molecules with multiparticle
      collision dynamics for the solvent. It is found that the reactivity of an
      individual active site in the multiple-active-site enzyme is reduced
      substantially, and this effect is analyzed and attributed to diffusive
      competition for the substrate among the different active sites in the enzyme. 

PMID- 24562417
TI  - Holocord syringomyelia secondary to tethered spinal cord associated with anterior
      sacral meningocele and tailgut cyst: case report and review of literature.
AB  - BACKGROUND AND IMPORTANCE: Anterior sacral meningoceles are lesions that are
      uncommonly reported and can be associated with other pathology including
      presacral masses, tethered spinal cord, and syringomyelia. Tethered spinal cord
      and syringomyelia can result in neurologic deficits, while large meningoceles and
      presacral masses can have gastroenterologic, urologic, reproductive, and
      oncologic consequences. CLINICAL PRESENTATION: The authors report a case of a 14
      year-old girl with an anterior sacral meningocele, tailgut cyst, and tethered
      cord with holocord syringomyelia who presented with a tethered cord syndrome,
      manifested by constipation, urinary retention, bilateral lower extremity
      weakness, and sensory deficits. After extensive radiographic and urodynamic
      workups were performed, the patient was treated by the neurosurgery and pediatric
      surgery teams with a posterior sagittal approach for cord detethering, resection
      of an intradural cystic mass, resection of the anterior sacral meningocele, and
      resection of the adjacent presacral mass. After surgical treatment, motor
      weakness and sensory deficits were resolved, though urinary symptoms persisted.
      The syrinx resolved after detethering alone. Pathology of the intradural cystic
      mass and the presacral mass inferior to the anterior sacral meningocele were
      consistent with tailgut cyst. CONCLUSION: The patient's clinical and surgical
      management are discussed, and a literature review related to anterior sacral
      meningoceles and their related pathologies is presented. An interdisciplinary
      approach is required for the best treatment of this constellation of findings.

PMID- 24562418
TI  - Who are the young adult Danish pre-drinkers, and why do they pre-drink before a
      night out?
AB  - AIMS: To reveal young Danes' main motive for pre-drinking and whether their
      motives and socio economic status can explain how much they pre-drink on an event
      specific night out. METHODS: A binary logistic and negative binomial regression
      models were used on a survey of 670 Danes (aged 18-35 years) conducted on-site in
      24 bars, clubs and pubs in four cities and towns in Denmark. RESULTS: Young males
      drink on average 12.3 and females 9.3 standard units (defined as 8 g of pure
      ethanol) of alcohol before a night out. Pre-drinking to be social is the most
      prevalent motive. Although lower income levels cannot explain whether a young
      person will pre-drink on an event-specific night out, young people's income level
      and their motives explain the quantities they consume. Lower-earning males who
      pre-drank to save money consumed larger quantities of alcohol at home, but lower
      earning females pre-drank larger quantities because they wanted to be out of
      control. CONCLUSIONS: Not only young people's motives for pre-drinking but also
      the price of off- and on-premises alcohol should be considered for outlining
      prevention strategies seeking to reduce the alcohol quantities that young people
      pre-drink before a night out.

PMID- 24562420
TI  - The 6-min walk test: an independent correlate of elevated tricuspid regurgitant
      jet velocity in children and young adult sickle cell patients.
AB  - Elevation of echocardiography-determined tricuspid regurgitant jet velocity (TRV)
      predicts high systolic pulmonary artery pressure. The present study tested the
      hypotheses that elevated tricuspid regurgitant jet velocity is associated with
      both hemolysis and hypoxia and abnormal 6-min walk test (6MWT) results. This
      study aims to correlate elevated TRV with different clinical laboratory findings
      and 6MWT and to find the independent predictors of increased TRV. A prospective
      study of 80 patients aged 5-25 years old with sickle cell disease (SCD) under
      basal conditions and 40 matched controls was conducted. Hemolytic analysis was
      assessed by the levels of lactate dehydrogenase, serum bilirubin, and
      reticulocyte count. Oxygen saturation determination using pulse oximeter and 6MWT
      were done. The overall prevalence of elevated TRV (>=2.5 m/s) was 28.75 %.
      Associated risk factors were older age (r = 0.28, p = 0.01), longer duration of
      disease (r = 0.25, p = 0.025), higher reticulocytic count (r = 0.344, p = 0.002),
      lower O2 saturation (r = -0.574, p = 0.0001), and shorter walked distance in 6MWT
      (r = -0.75, p = 0.0001). By multivariate logistic analysis, only the distance
      walked during 6MWT was the independent correlate of elevated TRV (odds ratio =
      0.85; 95 % CI = 0.74 to 0.98 p = 0.033). The study provides evidence for
      independent association of TRV with abnormal 6MWT results. The 6-min walk test
      can be used as noninvasive adjuvant tool for functional capacity assessment of
      SCD patients with elevated TRV. 

PMID- 24562419
TI  - The effects of weight and physical activity change over 20 years on later-life
      objective and self-reported disability.
AB  - BACKGROUND: Weight and health behaviours are known to affect physical disability;
      however the evidence exploring the impact of changes to these lifestyle factors
      over the life course on disability is inconsistent. We aimed to explore the roles
      of weight and activity change between mid and later life on physical disability.
      METHODS: Baseline and 20-year clinical follow-up data were collected from 1418
      men and women, aged 58-88 years at follow-up, as part of a population-based
      observational study based in north-west London. At clinic, behavioural data were
      collected by questionnaire and anthropometry measured. Disability was assessed
      using a performance-based locomotor function test and self-reported
      questionnaires on functional limitation and basic activities of daily living
      (ADLs). RESULTS: At follow-up, 39% experienced a locomotor dysfunction, 24% a
      functional limitation and 17% an impairment of ADLs. Weight gain of 10-20% or
      >20% of baseline, but not weight loss, were associated with increased odds of a
      functional limitation [odds ratio (OR) 1.69, 95% confidence interval (CI) 1.14
      2.49 and OR 2.74, 1.55-4.83, respectively], after full adjustment for covariates.
      The same patterns were seen for the other disability outcomes. Increased physical
      activity reduced, and decreased physical activity enhanced the likelihood of
      disability, independent of baseline behaviours and adiposity. The adverse effects
      of weight gain appeared to be lessened in the presence of increased later-life
      physical activity. CONCLUSION: Weight and activity changes between mid and later
      life have strong implications for physical functioning in older groups. These
      findings reinforce the importance of the maintenance of healthy weight and
      behaviour throughout the life course, and the need to promote healthy lifestyles
      across population groups.

PMID- 24562421
TI  - Micropapillary component in gastric adenocarcinoma: an aggressive variant
      associated with poor prognosis.
AB  - BACKGROUND: Adenocarcinomas with a micropapillary component (MPC) have been
      described as an unusual morphological variant in various organs. However, few
      reports have described MPCs in gastric carcinomas, and the clinicopathological
      features of MPC are unclear. METHODS: Immunohistochemistry was used to detect the
      expression of epithelial membrane antigen, CK7, CK20, p53, epidermal growth
      factor receptor, beta-catenin, c-erbB-2, and Ki-67. Correlation of the MPC to
      tumor stage, lymph node metastasis, and lymphovascular invasion was performed
      using Fisher's exact test. Kaplan-Meier estimates were used to analyze overall
      survival. RESULTS: Immunohistochemical staining demonstrated that micropapillary
      and conventional gastric carcinomas showed similar positivity rates for all
      markers. However, aberrant expression of E-cadherin was detected in the tumors
      with MPCs without immunoreactivity in the stroma face. Epithelial membrane
      antigen showed the characteristic inside-out staining pattern of MPCs. Lymphatic
      invasion (P = 0.003), venous invasion (P = 0.017), lymph node metastasis (P =
      0.014), and tumor stage (P = 0.022) were significantly increased in patients with
      MPCs when compared with conventional adenocarcinomas. MPC subtype II had a
      significantly higher frequency of lymph node metastasis than subtype I (P =
      0.014). However, the proportion of MPC was not associated with lymph node
      metastases (P = 0.136). Overall survival of patients with an MPC was
      significantly shorter than that of patients with conventional adenocarcinomas (P
      = 0.031). In addition, overall survival was significantly lower in patients with
      a subtype II MPC growth pattern than in those with subtype I MPC in gastric
      carcinomas (P = 0.040). CONCLUSION: Gastric adenocarcinomas with MPC appear to be
      an aggressive variant associated with a poor prognosis. MPCs occurring in gastric
      adenocarcinomas should be included in surgical pathology reports, even if the
      proportion of MPC in the lesions is very low in the lesion.

PMID- 24562422
TI  - Gold rotor bead tracking for high-speed measurements of DNA twist, torque and
      extension.
AB  - Single-molecule measurements of DNA twist and extension have been used to reveal
      physical properties of the double helix and to characterize structural dynamics
      and mechanochemistry in nucleoprotein complexes. However, the spatiotemporal
      resolution of twist measurements has been limited by the use of angular probes
      with high rotational drag, which prevents detection of short-lived intermediates
      or small angular steps. We introduce gold rotor bead tracking (AuRBT), which
      yields >100* improvement in time resolution over previous techniques. AuRBT
      employs gold nanoparticles as bright low-drag rotational and extensional probes,
      which are monitored by instrumentation that combines magnetic tweezers with
      objective-side evanescent darkfield microscopy. Our analysis of high-speed
      structural dynamics of DNA gyrase using AuRBT revealed an unanticipated transient
      intermediate. AuRBT also enables direct measurements of DNA torque with >50*
      shorter integration times than previous techniques; we demonstrated high
      resolution torque spectroscopy by mapping the conformational landscape of a Z
      forming DNA sequence. 

PMID- 24562423
TI  - Identification of small molecules that support human leukemia stem cell activity
      ex vivo.
AB  - Leukemic stem cells (LSCs) are considered a major cause of relapse in acute
      myeloid leukemia (AML). Defining pathways that control LSC self-renewal is
      crucial for a better understanding of underlying mechanisms and for the
      development of targeted therapies. However, currently available culture
      conditions do not prevent spontaneous differentiation of LSCs, which greatly
      limits the feasibility of cell-based assays. To overcome these constraints we
      conducted a high-throughput chemical screen and identified small molecules that
      inhibit differentiation and support LSC activity in vitro. Similar to reports
      with cord blood stem cells, several of these compounds suppressed the aryl
      hydrocarbon receptor (AhR) pathway, which we show to be inactive in vivo and
      rapidly activated ex vivo in AML cells. We also identified a compound, UM729,
      that collaborates with AhR suppressors in preventing AML cell differentiation.
      Together, these findings provide newly defined culture conditions for improved ex
      vivo culture of primary human AML cells. 

PMID- 24562425
TI  - Profiles of problematic behaviors across adolescence: covariations with
      indicators of positive youth development.
AB  - Previous analyses of data from the 4-H Study of Positive Youth Development (PYD)
      have examined concurrent trajectories of positive development and risk/problem
      behaviors among adolescents, finding complex and not necessarily inverse
      relationships among them. In this article, we expand on prior research by
      employing a person-centered approach to modeling risk behaviors, assessing
      development from approximately 6th grade through 12th grade among 4,391
      adolescents (59.9% female). Latent profiles involving the problematic behaviors
      of delinquency, depressive symptoms, substance use, sexual activity, disordered
      eating behaviors, and bullying were then assessed for concurrent relationships
      with the Five Cs of PYD: Competence, Confidence, Character, Caring, and
      Connection. We found six latent profiles, based primarily on mental health,
      aggression, and alcohol use, with significant differences in Confidence levels
      among many of the profiles, as well as some differences in the four other Cs. We
      discuss directions for future research and implications for application to youth
      policies and programs.

PMID- 24562426
TI  - Genetic diversity of hepatitis C virus quasispecies in chronic renal failure
      patients in Midwest Brazil.
AB  - Hepatitis C virus (HCV) quasispecies constitute a dynamic population in a
      continuous process of variation and selection. To investigate effect of the
      immune system on the genetic variability of HCV, we compared the hypervariable
      region 1 (HVR1) of immunosuppressed patients with chronic renal failure (CRF
      group) to immunocompetent patients with HCV chronic infection (control group).
      The HVR1 from ten samples of each group was amplified, cloned and sequenced. The
      HCV quasispecies from the control group had a higher frequency of variable sites
      in HVR1 (83.9 % vs 59.3 %, p < 0.05), as well as a greater diversity within
      (intra-patient) and between samples, compared to the CRF group. The clustering of
      the majority of the quasispecies of the CRF group in the phylogenetic tree also
      showed the limited diversity of the quasispecies in immunosuppressed patients.
      Moreover, a higher variability of amino acids at positions 384, 386, 391, 394,
      397, 398, 400, 405 and 410 was observed in the control group than in the CRF
      group, which showed a greater variability only at position 388 (p < 0.05). These
      data corroborates the hypothesis that the major selective pressure factor is the
      immune system, which promotes a high degree of diversity in the viral progeny and
      contributes to a constant evolution of HCV.

PMID- 24562424
TI  - Sleep-spindle detection: crowdsourcing and evaluating performance of experts, non
      experts and automated methods.
AB  - Sleep spindles are discrete, intermittent patterns of brain activity observed in
      human electroencephalographic data. Increasingly, these oscillations are of
      biological and clinical interest because of their role in development, learning
      and neurological disorders. We used an Internet interface to crowdsource spindle
      identification by human experts and non-experts, and we compared their
      performance with that of automated detection algorithms in data from middle- to
      older-aged subjects from the general population. We also refined methods for
      forming group consensus and evaluating the performance of event detectors in
      physiological data such as electroencephalographic recordings from
      polysomnography. Compared to the expert group consensus gold standard, the
      highest performance was by individual experts and the non-expert group consensus,
      followed by automated spindle detectors. This analysis showed that crowdsourcing
      the scoring of sleep data is an efficient method to collect large data sets, even
      for difficult tasks such as spindle identification. Further refinements to
      spindle detection algorithms are needed for middle- to older-aged subjects. 

PMID- 24562427
TI  - Genetic manipulation of a transcription-regulating sequence of porcine
      reproductive and respiratory syndrome virus reveals key nucleotides determining
      its activity.
AB  - The factors that determine the transcription-regulating sequence (TRS) activity
      of porcine reproductive and respiratory syndrome virus (PRRSV) remain largely
      unclear. In this study, the effect of mutagenesis of conserved C nucleotides at
      positions 5 and 6 in the leader TRS (TRS-L) and/or canonical body TRS7 (TRS-B7)
      on the synthesis of subgenomic (sg) mRNA and virus infectivity was investigated
      in the context of a type 2 PRRSV infectious cDNA clone. The results showed that a
      double C mutation in the leader TRS completely abolished sg mRNAs synthesis and
      virus infectivity, but a single C mutation did not. A single C or double C
      mutation in TRS-B7.1 or/and TRS-B7.2 impaired or abolished the corresponding sg
      mRNA synthesis. Introduction of identical mutations in the leader and body TRSs
      partially restored sg mRNA7.1 and/or sg mRNA7.2 transcription, indicating that
      the base-pairing interaction between sense TRS-L and cTRS-B is a crucial factor
      influencing sg mRNA synthesis. Analysis of the mRNA leader-body junctions of
      mutants provided evidence for a mechanism of discontinuous minus-strand
      transcription. This study also showed that mutational inactivation of TRS-B7.1 or
      TRS-B7.2 did not affect the production of infectious progeny virus, and the sg
      mRNA formed from each of them could express N protein. However, TRS-B7.1 plays
      more important roles than TRS-B7.2 in maintaining the growth characteristic of
      type 2 PRRSV. These results provide more insight into the molecular mechanism of
      genome expression and subgenomic mRNA transcription of PRRSV. 

PMID- 24562428
TI  - Comparison of digene hybrid capture 2, GeneMatrix PapilloScreen, and a PCR
      sequencing assay in detecting high-risk and probable high-risk oncogenic HPV
      genotypes in specimens from Korean women.
AB  - Most cervical cancers are caused by 15 high-risk (HR) and three probable high
      risk (pHR) oncogenic types of human papillomavirus (HPV). However, current
      commercial HR HPV screening test products do not include pHR HPV genotypes.
      Recently, PapilloScreen has been developed to detect the 15 HR and three pHR HPV
      types. In this study, we evaluated the concordance levels and clinical
      performance of Hybrid Capture 2 (HC2), PapilloScreen, and a PCR sequencing assay
      in detecting HR and pHR HPV. The PapilloScreen (96.8 %) and PCR sequencing assay
      (96.8 %) demonstrated higher sensitivity than HC2 (80.7 %) for detecting HR and
      pHR HPV. The three assays showed similar specificities and positive or negative
      predictive values. The concordance levels were 86.5 % (kappa = 0.68) and 86.5 %
      (kappa = 0.67) between HC2 and PapilloScreen and between HC2 and PCR sequencing,
      respectively. A near-perfect concordance was observed between PapilloScreen and
      PCR sequencing (97.8 %, kappa = 0.95). Overall, the agreement between the three
      assays suggests that the results obtained by the HC2 assay are more often
      discordant (12.6 %) than the PCR-based tests. In conclusion, PapilloScreen is
      highly sensitive for detecting high-grade CIN or cervical cancer. The
      PapilloScreen assay should be considered an accurate and sensitive method for
      detecting HR and pHR HPV infections and an epidemiological tool for prevalence
      studies as well as early diagnosis and intervention in HR and pHR HPV infections.

PMID- 24562429
TI  - Novel circular single-stranded DNA virus from turkey faeces.
AB  - Recently, a novel group of unclassified single-stranded (ss) circular small DNA
      viruses (called stool-associated circular virus; SCV) were identified in fecal
      samples of three mammalian species, namely, chimpanzee (ChiSCV), pig (PoSCV) and
      cattle (BoSCV). In this study, a novel genomic relative of stool-associated
      circular virus (TuSCV, KF880727) was detected in faeces of an avian species,
      namely, domestic turkey (Meleagris gallopavo). The complete TuSCV genome is 2479
      nt long and has two open reading frames (ORF), which are bidirectionally
      transcribed and separated by intergenic regions. The ORF1 (replicase) and ORF2
      (capsid) proteins have 77 % and 48 % aa sequence identity to different porcine
      origin SCVs.

PMID- 24562443
TI  - Validation of the Consensus-Definition for Cancer Cachexia and evaluation of a
      classification model--a study based on data from an international multicentre
      project (EPCRC-CSA).
AB  - BACKGROUND: Weight loss limits cancer therapy, quality of life and survival.
      Common diagnostic criteria and a framework for a classification system for cancer
      cachexia were recently agreed upon by international consensus. Specific
      assessment domains (stores, intake, catabolism and function) were proposed. The
      aim of this study is to validate this diagnostic criteria (two groups: model 1)
      and examine a four-group (model 2) classification system regarding these domains
      as well as survival. PATIENTS AND METHODS: Data from an international patient
      sample with advanced cancer (N = 1070) were analysed. In model 1, the diagnostic
      criteria for cancer cachexia [weight loss/body mass index (BMI)] were used. Model
      2 classified patients into four groups 0-III, according to weight loss/BMI as a
      framework for cachexia stages. The cachexia domains, survival and
      sociodemographic/medical variables were compared across models. RESULTS: Eight
      hundred and sixty-one patients were included. Model 1 consisted of 399 cachectic
      and 462 non-cachectic patients. Cachectic patients had significantly higher
      levels of inflammation, lower nutritional intake and performance status and
      shorter survival. In model 2, differences were not consistent; appetite loss did
      not differ between group III and IV, and performance status not between group 0
      and I. Survival was shorter in group II and III compared with other groups. By
      adding other cachexia domains to the model, survival differences were
      demonstrated. CONCLUSION: The diagnostic criteria based on weight loss and BMI
      distinguish between cachectic and non-cachectic patients concerning all domains
      (intake, catabolism and function) and is associated with survival. In order to
      guide cachexia treatment a four-group classification model needs additional
      domains to discriminate between cachexia stages.

PMID- 24562444
TI  - Tumor factors predictive of response to hypofractionated radiotherapy in a
      randomized trial following breast conserving therapy.
AB  - PURPOSE: To determine whether tumor grade, molecular subtype and hypoxia predict
      response to hypofractionated versus standard radiotherapy (RT) following breast
      conserving surgery (BCS) for node-negative breast cancer in a randomized
      controlled trial (RCT). PATIENTS AND METHODS: Formalin-fixed paraffin-embedded
      (FFPE) tumor blocks were available on 989 of 1234 patients enrolled in the
      Hypofractionation Whole Breast Irradiation (HWBI) Trial. A central pathology
      review and assessment of tumor grade using the Nottingham grading system was
      carried out. Tumors were classified by molecular subtype as luminal A, luminal B,
      HER2 enriched, basal-like or unclassified using a six-biomarker panel; ER, PR,
      HER-2, Ki67, CK5/6 and EGFR. Tumors were also classified as hypoxic based on the
      expression of HIF1alpha, CAIX or GLUT-1. The primary end point was local
      recurrence (LR). RESULTS: Median follow-up was 12 years. In the multivariable Cox
      model, molecular subtype was the only factor predictive of LR, the 10-year
      cumulative incidence was 4.5% for luminal A and basal-like, 7.9% for luminal B
      and 16.9% for HER-2 enriched tumors (P < 0.01). Tumor grade, molecular subtype or
      hypoxia did not predict response to hypofractionation. CONCLUSIONS: In women
      enrolled in the HWBI trial following BCS tumor molecular subtype predicted LR.
      However tumor grade, molecular subtype and hypoxia did not predict response to
      hypofractionation suggesting that patients with node-negative breast tumors of
      all grades and molecular subtypes may be safely treated with hypofractionated RT
      regimens.

PMID- 24562445
TI  - Intensity-modulated radiation therapy leads to survival benefit only in patients
      with high-risk prostate cancer: a population-based study.
AB  - BACKGROUND: During the last years, there has been a rapid adoption of intensity
      modulated radiation therapy (IMRT) in patients with prostate cancer (PCa),
      despite the lack of randomized trials evaluating its effectiveness. The aim of
      our study was to evaluate the survival benefit associated with IMRT in patients
      with PCa. PATIENTS AND METHODS: Overall, 42 483 patients with PCa treated with
      IMRT or initial observation between 2001 and 2007 within the Surveillance,
      Epidemiology, and End Results (SEER)-Medicare were evaluated. Patients in both
      treatment arms were matched using propensity-score methodology. After propensity
      score matching, 19 064 patients remained in our analyses. Eight-year cancer
      specific mortality (CSM) rates were estimated, and the number needed to treat
      (NNT) was calculated. Competing risks regression analyses tested the relationship
      between treatment type and CSM. RESULTS: Overall, the 8-year CSM rates were 3.4%
      and 4.1% for patients treated with IMRT versus initial observation, respectively
      (P < 0.001). The corresponding 8-year NNT was 142. In patients with
      low/intermediate-risk disease, IMRT was not associated with lower CSM rates
      compared with observation (P = 0.7). In patients with high-risk disease, the 8
      year CSM rates for IMRT versus observation were 5.8% versus 10.5%, respectively
      (P < 0.001). The corresponding NNT was 21. When high-risk patients were
      stratified according to age (<73 versus >=73), and Charlson comorbidity index
      (<=1 versus >1) the 8-year CSM rates for IMRT versus observation were 4.3% versus
      9.4% and 6.9% versus 11.9% and 5.3% versus 11.4% and 6.1% versus 10.1%,
      respectively (all Ps < 0.001). The corresponding NNTs were 19, 21, 16, and 25,
      respectively. In multivariate analyses, the protective effect of IMRT was more
      evident in high-risk patients with younger age and lower comorbidities.
      CONCLUSIONS: IMRT leads to a survival advantage only in patients with high-risk
      disease. Conversely, patients with low/intermediate-risk disease did not benefit
      from IMRT at 8-year follow-up.

PMID- 24562446
TI  - 2nd ESMO Consensus Conference on Lung Cancer: early-stage non-small-cell lung
      cancer consensus on diagnosis, treatment and follow-up.
AB  - To complement the existing treatment guidelines for all tumour types, ESMO
      organises consensus conferences to focus on specific issues in each type of
      tumour. The 2nd ESMO Consensus Conference on Lung Cancer was held on 11-12 May
      2013 in Lugano. A total of 35 experts met to address several questions on non
      small-cell lung cancer (NSCLC) in each of four areas: pathology and molecular
      biomarkers, first-line/second and further lines in advanced disease, early-stage
      disease and locally advanced disease. For each question, recommendations were
      made including reference to the grade of recommendation and level of evidence.
      This consensus paper focuses on early-stage disease. 

PMID- 24562447
TI  - Which threshold for ER positivity? a retrospective study based on 9639 patients.
AB  - BACKGROUND: Guidelines for the use of chemotherapy and endocrine therapy recently
      recommended that estrogen receptor (ER) status be considered positive if >=1% of
      tumor cells demonstrate positive nuclear staining by immunohistochemistry. In
      clinical practice, a range of thresholds are used; a common one is 10%
      positivity. Data addressing the optimal threshold with regard to the efficacy of
      endocrine therapy are lacking. In this study, we compared patient, tumor,
      treatment and survival differences among breast cancer patients using ER
      positivity thresholds of 1% and 10%. METHODS: The study population consisted of
      patients with primary breast carcinoma treated at our center from January 1990 to
      December 2011 and whose records included complete data on ER status. Patients
      were separated into three groups: >=10% positive staining for ER (ER-positive
      >=10%), 1%-9% positive staining for ER (ER-positive 1%-9%) and <1% positive
      staining (ER-negative). RESULTS: Of 9639 patients included, 80.5% had tumors that
      were ER-positive >=10%, 2.6% had tumors that were ER-positive 1%-9% and 16.9% had
      tumors that were ER-negative. Patients with ER-positive 1%-9% tumors were younger
      with more advanced disease compared with patients with ER-positive >=10% tumors.
      At a median follow-up of 5.1 years, patients with ER-positive 1%-9% tumors had
      worse survival rates than did patients with ER-positive >=10% tumors, with and
      without adjustment for clinical stage and grade. Survival rates did not differ
      significantly between patients with ER-positive 1%-9% and ER-negative tumors.
      CONCLUSIONS: Patients with tumors that are ER-positive 1%-9% have clinical and
      pathologic characteristics different from those with tumors that are ER-positive
      >=10%. Similar to patients with ER-negative tumors, those with ER-positive 1%-9%
      disease do not appear to benefit from endocrine therapy; further study of its
      clinical benefit in this group is warranted. Also, there is a need to better
      define which patients of this group belong to basal or luminal subtypes.

PMID- 24562448
TI  - Phase II study of neoadjuvant therapy with docetaxel, cisplatin, panitumumab, and
      radiation therapy followed by surgery in patients with locally advanced
      adenocarcinoma of the distal esophagus (ACOSOG Z4051).
AB  - BACKGROUND: Preoperative chemoradiotherapy (CRT) improves outcomes in patients
      with locally advanced but resectable adenocarcinoma of the esophagus. ACOSOG
      Z4051 evaluated CRT with docetaxel, cisplatin, and panitumumab (DCP) in this
      patient group with a primary end point of a pathologic complete response (pCR)
      >=35%. PATIENTS AND METHODS: From 15 January 2009 to 22 July 2011, 70 patients
      with locally advanced but resectable distal esophageal adenocarcinoma were
      enrolled. Patients received docetaxel (40 mg/m(2)), cisplatin (40 mg/m(2)), and
      panitumumab (6 mg/kg) on weeks 1, 3, 5, 7, and 9 with RT (5040 cGy, 180 cGy/day *
      28 days) beginning week 5. Resection was planned after completing CRT. PCR was
      defined as no viable residual tumor cells. Secondary objectives included near-pCR
      (<=10% viable cancer cells), toxicity, and overall and disease-free survival.
      Adverse events were graded using the CTCAE Version 3.0. RESULTS: Five of 70
      patients were ineligible. Of 65 eligible patients (59 M; median age 61), 11 did
      not undergo surgery, leaving 54 assessable. PCR rate was 33.3% and near-pCR was
      20.4%. Secenty-three percent of patients completed DCP (n = 70) and 92% completed
      RT. 48.5% had toxicity >=grade 4. Lymphopenia (43%) was most common. Operative
      mortality was 3.7%. Adult respiratory distress syndrome was encountered in two
      patients (3.7%). At median follow-up of 26.3 months, median overall survival was
      19.4 months and 3-year overall survival was 38.6% (95% confidence interval 24.5%
      to 60.8%). CONCLUSIONS: Neoadjuvant CRT with DCP is active (pCR + near-pCR =
      53.7%) but toxicity is significant. Further evaluation of this regimen in an
      unselected population is not recommended. CLINICALTRIALSGOV IDENTIFIER:
      NCT00757172.

PMID- 24562449
TI  - SPARC expression in resected pancreatic cancer patients treated with gemcitabine:
      results from the CONKO-001 study.
AB  - BACKGROUND: Previous investigations in pancreatic cancer suggested a prognostic
      role for secreted protein acidic and rich in cysteine (SPARC) expression in the
      peritumoral stroma but not for cytoplasmic SPARC expression. The aim of this
      study was to evaluate the impact of SPARC expression in pancreatic cancer
      patients treated with gemcitabine compared with untreated patients. PATIENTS AND
      METHODS: CONKO-001 was a prospective randomized phase III study investigating the
      role of adjuvant gemcitabine when compared with observation. Tissue samples of
      160 patients were available for SPARC immunohistochemistry on tissue microarrays
      to evaluate its impact on patient outcome. RESULTS: Strong stromal SPARC
      expression was associated with worse disease-free survival (DFS) and overall
      survival (OS) in the overall study population (DFS: P = 0.005, OS: P = 0.033).
      Its negative prognostic impact was restricted to patients treated with
      gemcitabine (DFS: P = 0.007, OS: P = 0.006). High cytoplasmic SPARC expression
      also was associated with worse patient outcome (DFS: P = 0.041, OS: P = 0.011).
      Again the effect was restricted to patients treated with gemcitabine (DFS: P =
      0.002, OS: P = 0.003). In multivariable analysis, SPARC expression was
      independently predictive of patient outcome. CONCLUSIONS: Our data confirm the
      prognostic significance of SPARC expression after curatively intended resection.
      The negative prognostic impact was restricted to patients who received adjuvant
      treatment with gemcitabine, suggesting SPARC as a predictive marker for response
      to gemcitabine.

PMID- 24562450
TI  - Controversial issues in early-stage breast cancer: a global collaborative survey,
      supported by the European Society for Medical Oncology (ESMO).
AB  - BACKGROUND: To explore the current clinical management of early-stage breast
      cancer (BC) patients, identify areas of controversy, and interrogate how treating
      physicians implement latest advances. METHODS: We conducted a 27-item survey,
      disseminated in two stages: paper distribution at selected BC sessions at the
      ESMO 2012 Congress, and dedicated mailings to ESMO members. Descriptive
      statistical analysis and logistic regression analysis were applied to explore
      potential associations between the demographic characteristics of the
      participants and replies. RESULTS: A total of 512 physicians from 79 countries
      participated in the study, accounting for 465 (91%) fully completed
      questionnaires. The majority of the participants were ESMO members (66%), medical
      oncologists (86.5%), and working in multidisciplinary teams (91.6%).
      Heterogeneous results were captured, such as the following: 40.9% of the
      participants consider no genetic test useful for making adjuvant treatment
      decisions; 15.3% consider PET-CT a useful imaging modality for staging; 68.8%
      consider that postmenopausal patients with hormone receptor positive disease
      should always be offered an aromatase inhibitor as part of their adjuvant
      therapy; 78.7% prefer to administer trastuzumab concurrently with the taxane
      component of chemotherapy; and 27% would consider bevacizumab in the neoadjuvant
      setting. The logistic regression analysis did not identify any strong predictor
      of the probability of giving a reply fully compatible with evidence in the
      literature. CONCLUSION: This survey captures clinical practice and whether the
      latest research advances are implemented in the treatment of early-stage BC by an
      extended number of physicians. Significant individual differences were found.
      Areas of controversy were detected, and they deserve further exploration in order
      to generate 'tailored' educational tools, with the final goal being the
      standardization of the treatment of early-stage BC patients.

PMID- 24562451
TI  - Larvicidal, ovicidal, and oviposition-deterrent activities of four plant extracts
      against three mosquito species.
AB  - In mosquito control programs, insecticides of botanical origin have the potential
      to eliminate eggs, larvae, and adults. So, the larvicidal, ovicidal, and
      oviposition-deterrent activities of petroleum ether and ethyl acetate extracts of
      the leaves of Eugenia jambolana, Solidago canadensis, Euodia ridleyi, and
      Spilanthes mauritiana were assayed against the three vector mosquito species,
      namely Anopheles stephensi, Aedes aegypti, and Culex quinquefasciatus. The larval
      bioassay was conducted following the World Health Organization method. The
      maximum larval mortality was found with ethyl acetate extract of S. mauritiana
      against the larvae of A. stephensi, A. aegypti, and C. quinquefasciatus with LC50
      values of 11.51, 28.1, 14.10 ppm, respectively. The mean percent hatchability of
      the ovicidal activity was observed at 48-h post-treatment. The percent
      hatchability was found to be inversely proportional to the concentration of the
      extract and directly proportional to the number of eggs. The flower head extract
      of S. mauritiana gave 100% mortality followed by E. ridleyi, S. canadensis, and
      E. jambolana against the eggs of the three mosquito vectors. For oviposition
      deterrent effect, out of the five concentrations tested (20, 40, 60, 80, and 100
      ppm), the concentration of 100 ppm showed a significant egg laying-deterrent
      capacity. The oviposition activity index value of E. jambolana, E. ridleyi, S.
      canadensis, and S. mauritiana against A. aegypti, A. stephensi, C.
      quinquefasciatus at 100 ppm were -0.71, -0.71, -0.90, -0.93, -0.85, -0.91, -1, 
      1, -0.71, -0.85, -1, and -1, respectively. These results suggest that the
      leaf/flower extracts of certain local plants have the potential to be developed
      as possible eco-friendly means for the control of mosquitoes.

PMID- 24562452
TI  - Photocatalysis of fenoxycarb over silver-modified zeolites.
AB  - Two samples of silver doped into zeolite Y were prepared and characterized. ICP
      and SEM-EDS analysis indicate that the AgY1 sample contains twice the amount of
      silver compared to the AgY2 sample. Solid state luminescence spectroscopy shows
      variations in the emission modes of the site-selective luminescence where various
      luminophores might be excited upon selecting the proper excitation energy. The
      selected material effectively decomposed the pesticide fenoxycarb in aqueous
      solution. The photodecomposition of fenoxycarb reached 80 % upon irradiation for
      60 min in the presence of the AgY1 catalyst. 2-(4-Phenoxy-phenoxy)ethyl] carbamic
      acid (1) and 1-amine-2-(phenoxy-4-ol) ethane (2) were identified as products for
      both uncatalyzed solution and the catalyzed fenoxycarb with AgY2 catalyst.
      Whereas, compound (2) was the only product identified in the catalyzed reaction
      with AgY1.

PMID- 24562453
TI  - Structure-activity analysis of harmful algae inhibition by congeneric compounds:
      case studies of fatty acids and thiazolidinediones.
AB  - The occurrence of harmful algal blooms has been increasing significantly around
      the world. In order to ensure the safety of drinking water, procedures to screen
      potential materials as effective algicides are needed, and predictive methods
      which save both the labor and time compared with traditional experimental
      approaches, are particularly desirable. In this study, data from previous studies
      on the algal-growth inhibitory action of two kinds of compounds, namely, the
      action of fatty acids and thiazolidinediones on the harmful algae Heterosigma
      akashiwo and Chattonella marina, were modeled using multiple linear regression
      (MLR) based on quantitative structure-activity relationships (QSAR). The models
      were shown to have highly predictive ability and stability, and provided insight
      into the inhibitory mechanisms of congeneric compounds. The main descriptors in
      the fatty-acid models were the Connolly accessible area and the number of
      rotatable bonds, illustrating that molecular surface area and shape are important
      in their algicidal actions. In the thiazolidinedione models, the critical volume,
      octanol-water partition coefficient (LogP), and Connolly solvent-excluded volume
      were found to be significant, indicating that hydrophobicity, substituent group
      size, and mode of action are mechanistically important. Our results showed the
      algicidal activity of a series of compounds on different algae could be modeled,
      and each model is efficacious for compounds that fall into the application domain
      of the QSAR model. This work demonstrates how reliable predictions of the
      algicidal activity of novel compounds and explanations of their inhibitory
      mechanisms can be obtained. 

PMID- 24562454
TI  - Optimizing stabilization of waste-activated sludge using Fered-Fenton process and
      artificial neural network modeling (KSOFM, MLP).
AB  - Sludge management is a fundamental activity in accordance with wastewater
      treatment aims. Sludge stabilization is always considered as a significant step
      of wastewater sludge handling. There has been a progressive development observed
      in the approach to the novel solutions in this regard. In this research, based on
      own initially experimental results in lab-scale regarding Fered-Fenton processes
      in view of organic loading (volatile-suspended solids, VSS) removal efficiency, a
      combination of both methods towards proper improving of excess biological sludge
      stabilization was investigated. Firstly, VSS removal efficiency has been
      experimentally studied in lab-scale under different operational conditions taking
      into consideration pH [Fe(2+)]/[H2O2], detention time [H2O2], and current density
      parameters. Therefore, the correlations of the same parameters have been
      determined by utilizing Kohonen self-organizing feature maps (KSOFM). In
      addition, multi-layer perceptron (MLP) has been employed afterwards for a
      comprehensive evaluation of investigating parameters correlation and prediction
      aims. The findings indicated that the best proportion of iron to hydrogen
      peroxide and the optimum pH were 0.58 and 3.1, respectively. Furthermore, maximum
      retention time about 6 h with a hydrogen peroxide concentration of 1,568 mg/l and
      a current density of 650-750 mA results to the optimum VSS removal (efficiency
      equals to 81 %). The performance of KSOFM and MLP models is found to be
      magnificent, with correlation ranging (R) from 0.873 to 0.998 for the process
      simulation and prediction. Finally, it can be concluded that the Fered-Fenton
      reactor is a suitable efficient process to reduce considerably sludge organic
      load and mathematical modeling tools as artificial neural networks are impressive
      methods of process simulation and prediction accordingly.

PMID- 24562455
TI  - Spatial variations of concentrations of copper and its speciation in the soil
      rice system in Wenling of southeastern China.
AB  - Copper (Cu) is one of the essential elements for plant growth, while excessive Cu
      in soils has potential environmental risks. There is little information on
      spatial variation of Cu in practical paddy fields. This is now important for
      appropriate agricultural management. The spatial patterns of Cu, its fractions in
      soils, and its concentrations in rice were investigated in a typical rice
      production region-Wenling of southeastern China. A total of 96 pairs of rice
      grain and soil samples (0-15 cm) were collected. The total concentration of Cu
      and its fractions were very variable, with large skewness, kurtosis, and
      coefficient of variation (CV) values. Compared to the guideline value (50 mg kg(
      1)), Cu pollution in paddy fields was observed in the study area. All the
      measured Cu concentrations in rice were lower than 10 mg kg(-1), suggesting that
      they remained at a safe level. Spatial analyses including Moran's I index and
      geostatistics results indicated that high-high spatial patterns for both Cu in
      soils and rice were found in the northwest part, which was mainly related to
      industrial and E-waste dismantling activities. The low-low spatial patterns of Cu
      in the soil-rice system were located in the south part of study area. The cross
      correlogram results indicated that Cu concentration in rice was significantly
      spatially correlated with total Cu in soils, its fractions, and soil organic
      matter (SOM), but significantly negatively correlated with pH and electrical
      conductivity (EC). Most of the selected variables had a clear spatial correlation
      range with Cu in rice. The ranges of significant spatial correlation (p < 0.05)
      could be obtained and further used for dividing agricultural management zones.

PMID- 24562456
TI  - Plutonium partitioning in three-phase systems with water, granite grains, and
      different colloids.
AB  - Low-solubility contaminants with high affinity for colloid surfaces may form
      colloid-associated species. The mobile characteristics of this species are,
      however, ignored by the traditional sorption/distribution experiments in which
      colloidal species contributed to the immobile fraction of the contaminants
      retained on the solids as a result of centrifugation or ultrafiltration
      procedures. The mobility of the contaminants in subsurface environments might be
      underestimated accordingly. Our results show that colloidal species of (239)Pu in
      three-phase systems remained the highest percentages in comparison to both the
      dissolved species and the immobile species retained on the granite grains (solid
      phase), although the relative fraction of these three species depended on the
      colloid types. The real solid/liquid distribution coefficients (K s/d)
      experimentally determined were generally smaller than the traditional K s/d
      (i.e., the K s+c/d in this study) by ~1,000 mL/g for the three-phase systems with
      the mineral colloids (granite particle, soil colloid, or kaolinite colloid). For
      the humic acid system, the traditional K s/d was 140 mL/g, whereas the real K s/d
      was approximately zero. The deviations from the real solid/liquid K s/d were
      caused by the artificially increased immobile fraction of Pu. One has to be
      cautious in using K s/d-based transport models to predict the fate and transport
      of Pu in the environment.

PMID- 24562457
TI  - Herbicide clomazone effects on delta-aminolevulinic acid activity and metabolic
      parameters in Cyprinus carpio.
AB  - The objective of this study was to investigate delta-aminolevulinic acid (delta
      ALA-D) activity and metabolic parameters of Cyprinus carpio exposed to clomazone
      herbicide. Fish were exposed 2.5, 5, 10 and 20 mg L(-1) of clomazone for 192 h.
      Results indicated that delta-ALA-D activity was decreased in the gills at
      concentrations of 5 and 10 mg L(-1). Liver glycogen increased, while muscle and
      gill glycogen levels decreased at 5, 10 and 20 mg L(-1). Glucose was increased in
      the gills and plasma. Lactate decreased in the gills and liver and increased in
      the muscle. Protein and amino acids levels increased in the liver and gills and
      decreased in the muscle. At a clomazone concentration of 20 mg L(-1), ammonia
      increased in the gills and muscle and decreased in the liver. The results
      indicated that the metabolic parameters of glycogen, lactate, protein and amino
      acids in liver, muscle and gills, blood glucose levels, and the enzyme delta-ALA
      D in gills may be useful indicators of clomazone toxicity in carp.

PMID- 24562459
TI  - Large-scale bioreactor production of the herbicide-degrading Aminobacter sp.
      strain MSH1.
AB  - The Aminobacter sp. strain MSH1 has potential for pesticide bioremediation
      because it degrades the herbicide metabolite 2,6-dichlorobenzamide (BAM).
      Production of the BAM-degrading bacterium using aerobic bioreactor fermentation
      was investigated. A mineral salt medium limited for carbon and with an element
      composition similar to the strain was generated. The optimal pH and temperature
      for strain growth were determined using shaker flasks and verified in
      bioreactors. Glucose, fructose, and glycerol were suitable carbon sources for
      MSH1 (MU = 0.1 h(-1)); slower growth was observed on succinate and acetic acid
      (MU = 0.01 h(-1)). Standard conditions for growth of the MSH1 strain were defined
      at pH 7 and 25  degrees C, with glucose as the carbon source. In bioreactors (1
      and 5 L), the specific growth rate of MSH1 increased from MU = 0.1 h(-1) on
      traditional mineral salt medium to MU = 0.18 h(-1) on the optimized mineral salt
      medium. The biomass yield under standard conditions was 0.47 g dry weight
      biomass/g glucose consumed. An investigation of the catabolic capacity of MSH1
      cells harvested in exponential and stationary growth phases showed a degradation
      activity per cell of about 3 * 10(-9) MUg BAM h(-1). Thus, fast, efficient, large
      scale production of herbicide-degrading Aminobacter was possible, bringing the
      use of this bacterium in bioaugmentation field remediation closer to reality. 

PMID- 24562460
TI  - Dual-mode hydrodynamic railing and arraying of microparticles for multi-stage
      signal detection in continuous flow biochemical microprocessors.
AB  - Continuous flow particulate-based microfluidic processors are in critical demand
      for emerging applications in chemistry and biology, such as point-of-care
      molecular diagnostics. Challenges remain, however, for accomplishing biochemical
      assays in which microparticle immobilization is desired or required during
      intermediate stages of fluidic reaction processes. Here we present a dual-mode
      microfluidic reactor that functions autonomously under continuous flow conditions
      to: (i) execute multi-stage particulate-based fluidic mixing routines, and (ii)
      array select numbers of microparticles during each reaction stage (e.g., for
      optical detection). We employ this methodology to detect the inflammatory
      cytokine, interferon-gamma (IFN-gamma), via a six-stage aptamer-based sandwich
      assay. 

PMID- 24562461
TI  - AMPed up to treat prostate cancer: novel AMPK activators emerge for cancer
      therapy.
AB  - Despite recent advances in the treatment for metastatic prostatic adenocarcinoma,
      clinical management of this tumor type remains a major challenge, and there is as
      of yet no durable cure for advanced disease. Developing pathways that could be co
      targeted alongside the androgen receptor or that would otherwise thwart the
      development of the CRPC is a current translational and clinical priority. In this
      issue, a new study by Zadra et al identifies the energy sensor AMPK (5' AMP
      activated kinase) as a viable therapeutic target in prostate cancer. 

PMID- 24562462
TI  - Stent-retriever thrombectomy: impact on the future of interventional stroke
      treatment.
AB  - Endovascular treatment for acute ischemic stroke has evolved in the past years.
      The current development of stent-retriever thrombectomy is a landmark in the
      clinical treatment and study results of acute ischemic stroke. This review
      summarizes the recent study results, elucidates the shortcomings of endovascular
      stroke treatment, and takes the opportunity for an outlook on the role of stroke
      interventions in the future. 

PMID- 24562463
TI  - The influence of axial length on confocal scanning laser ophthalmoscopy and
      spectral-domain optical coherence tomography size measurements: a pilot study.
AB  - PURPOSE: To investigate the influence of axial length on SD-OCT and cSLO size
      measurements from the Heidelberg Spectralis. METHODS: In this pilot study, eight
      emmetropic pseudophakic eyes with subretinal visual implant were selected. The
      axial length was measured in three short (<22.5 mm), three medium (22.51-25.50
      mm) and two long (>25.52 mm) eyes. The known size of subretinal implant sensor
      field (2800 * 2800 MUm) was measured on 15 images per eye with cSLO and SD-OCT.
      RESULTS: The mean axial length was 20.8 +/- 0.8 mm in short eyes, 23.3 +/- 0.4 mm
      in medium eyes, and 26.3 +/- 0.5 mm in long eyes respectively. We found in short
      eyes, in medium eyes and in long eyes a mean value of sensor field size
      measurements from cSLO of 3327 +/- 9 MUm, 2800 +/- 9 MUm and 2589 +/- 12 MUm and
      from SD-OCT of 3328 +/- 9 MUm, 2800 +/- 12 MUm and 2585 +/- 19 MUm respectively.
      The size measurements decreased in SD-OCT and cSLO measurements with longer axial
      lengths significantly (p < 0.0001). CONCLUSION: The present findings demonstrate
      accuracy of the scaling in cSLO and SD-OCT measurements of the Heidelberg
      Spectralis for emmetropic medium eyes. The size measurements from SD-OCT to those
      from cSLO were approximately equal. Caution is recommended when comparing the
      measured values of short and long eyes with the normative database of the
      instrument. Further studies with larger sample sizes are needed to confirm
      findings.

PMID- 24562465
TI  - Effect of porcine chondrocyte-derived extracellular matrix on the pterygium in
      mouse model.
AB  - PURPOSE: To investigate the effect of porcine chondrocyte-derived extracellular
      matrix (PCDECM) on an experimental mouse model of human pterygial epithelial
      cells. METHODS: Cultured human pterygial epithelial cells (hPECs) were stained
      with pan-cytokeratin (CK), CK3/2p, vimentin, and CK13 antibodies to characterize
      the cells. A pterygium mouse model was developed by injecting 1X104 hPECs into
      the nasal subconjunctival space in athymic nude mice. PCDECM (25 mg/mL, 10 MUL)
      was injected into the nasal subconjunctival space in the right eye 7, 10 and 14
      days after the epithelial cell injection (PCDECM group). Image analysis was
      performed using ImageJ(r) to compare the lesion size. A histopathological
      analysis of the cornea was conducted to evaluate the state of the epithelium and
      the expression of pterygial epithelial cell markers. RESULTS: The isolated
      pterygial cells were positive for pan-CK, CK3/2p and vimentin, and they were
      negative for CK13 under immunofluorescence microscopy. On day 17 after epithelial
      cell injection, the size of the lesion compared to the entire cornea was
      increased to 37.1 % in the control group. However, in the PCDECM group, the
      lesion covered only 26.3 % of the entire cornea. The corneas of the pterygium
      mice showed an epithelium of irregular thickness, proliferation of the stroma,
      extracellular matrix breakdown and overexpression of pterygium-positive markers.
      However, these changes were significantly suppressed by the application of
      PCDEDM. CONCLUSIONS: Our findings suggest that PCDECM seems to suppress pterygial
      epithelial cell growth and it could be used as a promising biomaterial for the
      noninvasive treatment of pterygium.

PMID- 24562466
TI  - Anti-inflammatory action of isorhamnetin.

PMID- 24562464
TI  - Elevated percentage of HLA-DR+ and ICAM-1+ conjunctival epithelial cells in
      active Graves' orbitopathy.
AB  - BACKGROUND: To evaluate if conjunctival epithelial cells' expression of HLA-DR
      and ICAM-1 could be helpful as early topical markers of inflammation in Graves'
      orbitopathy (GO). METHODS: The ocular examination evaluated a clinical activity
      score (CAS) by assessment of clinical features, (e.g., eyelid or conjunctival
      inflammation, lid width, lid closure, proptosis, ocular motility). Conjunctival
      epithelial cell specimens for flow-cytometric evaluations of ICAM-I and HLADR
      expression were collected by impression cytology from ten eyes with active GO
      (CAS  >=  4 and duration  <=  12 months), from 15 eyes with Graves' disease (GD)
      without active GO (CAS 0-2) and from 15 normal specimens without any ocular
      disorders. RESULTS: The percentage of HLA-DR + conjunctival epithelial cells was
      significantly elevated in patients with active GO comparing to GD without active
      GO and healthy controls, 10.7 % (8.5-17.7) and 7.78 % (3.92-10.1) (p < 0.05) vs.
      control 4.89 % (3.5-5.5) (p < 0.005), respectively. The expression of ICAM - 1+
      conjunctival epithelial cells was greater only in patients with GO vs. controls,
      5.5 % (4.8-7.03) and 1.46 % (0.69-2.51) (p < 0.005), respectively. CONCLUSION:
      The percentage of HLA-DR+ and ICAM-1+ conjunctival epithelial cells in patients
      with the active GO may serve as a topical inflammation marker in Graves'
      orbitopathy.

PMID- 24562467
TI  - PGC-1alpha expression is increased in leukocytes in experimental acute
      pancreatitis.
AB  - Severe acute pancreatitis (AP) induces a systemic inflammatory disease that is
      responsible for high mortality rates, particularly when it is complicated by
      infection. Therefore, differentiating sepsis from the systemic inflammation
      caused by AP is a serious clinical challenge. Considering the high metabolic
      rates of leukocytes in response to stress induced by infection, we hypothesized
      that the transcription coactivator peroxisome proliferator-activated receptor
      gamma coactivator 1 (PGC-1alpha), a master regulator of mitochondrial biogenesis
      and function, would be distinctly expressed during inflammation or infection and,
      therefore, could constitute a useful marker to differentiate between these two
      conditions. Rats were subjected to injection of taurocholate into the main
      pancreatic duct, which caused a severe AP with high amylase levels and white
      blood cell counts. In these animals, a marked increase in PGC-1alpha mRNA levels
      in circulating leukocytes was observed 48 h after the surgical procedure, a time
      when bacteremia is present. Antibiotic treatment abolished PGC-1alpha up
      regulation. Moreover, PGC-1alpha expression was higher in peritoneal macrophages
      from animals subjected to a bacterial insult (cecal ligation and puncture) than
      in animals with AP. In isolated macrophages, we also observed that PGC-1alpha
      expression is more prominent in the presence of a phagocytic stimulus (zymosan)
      when compared to lipopolysaccharide-induced aseptic inflammation. Moreover,
      abolishing PGC-1alpha expression with antisense oligos impaired zymosan
      phagocytosis. Together, these findings suggest that PGC-1alpha is differentially
      expressed during aseptic inflammation and infection and that it is necessary for
      adequate phagocytosis. These results could be useful in developing new tests for
      differentiating infection from inflammation for clinical purposes in patients
      with AP. 

PMID- 24562469
TI  - Oral rehydration therapy in the second decade of the twenty-first century.
AB  - Oral rehydration solution (ORS) was established as the cornerstone of therapy for
      dehydration secondary to acute infectious diarrhea approximately 40 years ago.
      The efficacy of ORS is based on the ability of glucose to stimulate Na and fluid
      absorption in the small intestine via a cyclic AMP-independent process. Despite
      the establishment that ORS is the primary reason for the substantial reduction in
      morbidity and mortality from diarrhea in children in developing countries, the
      use of ORS has lagged for many reasons. This review highlights efforts to
      establish a major reformulation of ORS following the demonstration that short
      chain fatty acids (SCFA) stimulate colonic Na and fluid absorption by a cyclic
      AMP-independent mechanism. The addition of high-amylose maize starch (HAMS), a
      microbially-fermentable (or 'resistant') starch, to ORS results in delivery of
      non-absorbed carbohydrate to the colon where it is fermented to SCFA. To date,
      three randomized controlled trials with a HAMS-ORS in south India have
      demonstrated a substantial decrease in diarrhea duration in both adults and
      children hospitalized for acute diarrhea. Significant efforts are now underway to
      establish this dual-action, modified HAMS-hypoosmolar ORS solution as the
      standard ORS for the treatment of dehydration from acute diarrhea.

PMID- 24562470
TI  - Altered trophic pathway and parasitism in a native predator (Lepomis gibbosus)
      feeding on introduced prey (Dreissena polymorpha).
AB  - Populations of invasive species tend to have fewer parasites in their introduced
      ranges than in their native ranges and are also thought to have fewer parasites
      than native prey. This 'release' from parasites has unstudied implications for
      native predators feeding on exotic prey. In particular, shifts from native to
      exotic prey should reduce levels of trophically transmitted parasites. We tested
      this hypothesis in native populations of pumpkinseed sunfish (Lepomis gibbosus)
      in Lake Opinicon, where fish stomach contents were studied intensively in the
      1970s, prior to the appearance of exotic zebra mussels (Dreissena polymorpha) in
      the mid-1990s. Zebra mussels were common in stomachs of present-day pumpkinseeds,
      and stable isotopes of carbon and nitrogen confirmed their importance in long
      term diets. Because historical parasite data were not available in Lake Opinicon,
      we also surveyed stomach contents and parasites in pumpkinseed in both Lake
      Opinicon and an ecologically similar, neighboring lake where zebra mussels were
      absent. Stomach contents of pumpkinseed in the companion lake did not differ from
      those of pre-invasion fish from Lake Opinicon. The companion lake, therefore,
      served as a surrogate "pre-invasion" reference to assess effects of zebra mussel
      consumption on parasites in pumpkinseed. Trophically transmitted parasites were
      less species-rich and abundant in Lake Opinicon, where fish fed on zebra mussels,
      although factors other than zebra mussel consumption may contribute to these
      differences. Predation on zebra mussels has clearly contributed to a novel
      trophic coupling between littoral and pelagic food webs in Lake Opinicon. 

PMID- 24562471
TI  - Distance to semi-natural grassland influences seed production of insect
      pollinated herbs.
AB  - Marginal grassland fragments, such as road verges and field margins, may act as
      important supplemental habitats for grassland plants in the modern agricultural
      landscape. However, abundance of pollinators in such fragments has been found to
      decline with distance to larger natural and semi-natural habitats, and this could
      have corresponding effects on plant pollination. In this study, we performed a
      field experiment on road verges with three insect-pollinated grassland herbs to
      examine the relationship between distance to semi-natural grassland and plant
      reproductive success in two landscapes with contrasting farming intensities. In
      Lychnis viscaria and Lotus corniculatus, seed production tended to decrease with
      increasing distance to semi-natural grassland, but only in the landscape with
      high farming intensity. Seed production in Armeria maritima spp. maritima
      decreased with distance in both landscapes. Although many studies have
      investigated effects of natural habitat on crop pollination, little is known
      about the impact on pollination in native plants. The results from this study
      indicate that management of semi-natural grasslands improves not only
      biodiversity within the actual grassland but also pollination of native plants in
      the surrounding agricultural landscape. 

PMID- 24562473
TI  - Theoretical predictions on the role of the internal H3(+) rotation in the IR
      spectra of the H5(+) and D5(+) cations.
AB  - The IR spectra of the H5(+) and D5(+) cations in the mid- and far-IR spectral
      regions have been recently reported by experimentalists. These spectra show very
      rich vibrational patterns representing a challenge for state-of-the-art
      theoretical methods to provide definitive interpretations of them. Using a full
      dimensional quantum anharmonic treatment, within the MCTDH approach, together
      with ab initio potential and dipole moment surfaces, the predominant features in
      the spectra are assigned, completing an important part in previous theoretical
      and experimental comparisons. The internal rotation of the H3(+) unit by exciting
      the H3(+)-H2 stretching mode is found to correspond to the new calculated
      features at 1182, 1876, and 2139 cm(-1) of the H5(+) spectrum, leading to a
      consistent assignment with the experimental spectra. In the calculated spectra of
      both H5(+) and D5(+) clusters, the progressions in the H3(+)-H2 stretch of the
      shared proton and the in- and out-of- plane H3(+) rotation are demonstrated to be
      the main features. Such states are expected to play a central role in the low
      temperature hydrogen/deuterium proton hop/exchange H3(+) + H2 reactions. 

PMID- 24562472
TI  - Retained medullary cord confirmed by intraoperative neurophysiological mapping.
AB  - INTRODUCTION: A retained medullary cord (RMC) is a rare dysraphic malformation,
      recently described as a late arrest of secondary neurulation. RMC is also a
      severely tethering lesion. The critical role of intraoperative neurophysiology to
      safely manage a RMC has been only anecdotally reported. CASE REPORT: We describe
      the case of a RMC in a 1.5-year-old child with Currarino syndrome. At surgery, an
      apparently normal-looking spinal cord, stretched and tethered by a lipoma to the
      level of S2-S3, was observed. The border between the functional conus and the non
      functional RMC was defined through neurophysiological mapping. The cord was
      sharply interrupted at this level and untethered. A specimen was sent for
      pathology, which confirmed the presence of glial and neural elements. The post
      operative neurological exam was normal. CONCLUSION: Neurosurgical procedure for
      RMC should only be rendered with intraoperative neurophysiological mapping, as
      the anatomical judgment would not suffice to allow a safe cutting of these
      "normal-looking" neural structures.

PMID- 24562474
TI  - A genome scan for quantitative trait loci associated with Vibrio anguillarum
      infection resistance in Japanese flounder (Paralichthys olivaceus) by bulked
      segregant analysis.
AB  - A recent genetic linkage map was employed to detect quantitative trait loci
      (QTLs) associated with Vibrio anguillarum resistance in Japanese flounder. An F1
      family established and challenged with V. anguillarum in 2009 was used for QTL
      mapping. Of the 221 simple sequence repeat (SSR) markers used to detect
      polymorphisms in the parents of F1, 170 were confirmed to be polymorphic. The
      average distance between the markers was 10.6 cM. Equal amounts of genomic DNA
      from 15 fry that died early and from 15 survivors were pooled separately to
      constitute susceptible bulk and resistance bulk DNA. Bulked segregant analysis
      and QTL mapping were combined to detect candidate SSR markers and regions
      associated with the disease. A genome scan identified four polymorphic SSR
      markers, two of which were significantly different between susceptible and
      resistance bulk (P=0.008). These two markers were located in linkage group (LG)
      7; therefore, all the SSR markers in LG7 were genotyped in all the challenged fry
      by single marker analysis. Using two different models, 11-17 SSR markers were
      detected with different levels of significance. To confirm the associations of
      these markers with the disease, composite interval mapping was employed to
      genotype all the challenged individuals. One and three QTLs, which explained more
      than 60 % of the phenotypic variance, were detected by the two models. Two of the
      QTLs were located at 48.6 cM. The common QTL may therefore be a major candidate
      region for disease resistance against V. anguillarum infection.

PMID- 24562475
TI  - Structural characterization of a hypothetical protein: a potential agent involved
      in trimethylamine metabolism in Catenulispora acidiphila.
AB  - Catenulispora acidiphila is a newly identified lineage of actinomycetes that
      produces antimicrobial activities and represents a promising source of novel
      antibiotics and secondary metabolites. Among the discovered protein coding genes,
      68 % were assigned a putative function, while the remaining 32 % are genes
      encoding "hypothetical" proteins. Caci_0382 is one of the "hypothetical" proteins
      that has very few homologs. Sequence analysis shows that the protein belongs to
      the NTF2-like protein family. The structure of Caci_0382 demonstrates that it
      shares the same fold and has a similar active site as limonene-1,2-epoxide
      hydrolase, which suggests that it may have a related function. Using a
      fluorescence thermal shift assay, we identified stabilizing compounds that
      suggest potential natural ligands of Caci_0382. Using this information, we
      determined the crystal structure in complex with trimethylamine to provide a
      better understanding of the function of this uncharacterized protein. 

PMID- 24562476
TI  - Real-life effectiveness, safety, and tolerability of amlodipine/valsartan or
      amlodipine/valsartan/hydrochlorothiazide single-pill combination in patients with
      hypertension from Pakistan.
AB  - OBJECTIVE: EXCITE (clinical EXperienCe of amlodIpine and valsarTan in
      hypErtension) evaluated the real-life effectiveness, safety, and tolerability of
      single-pill combinations (SPCs) of amlodipine/valsartan (Aml/Val) and
      amlodipine/valsartan/hydrochlorothiazide (Aml/Val/HCTZ) in patients with
      hypertension from 13 countries in the Middle East and Asia. Here, we present data
      from Pakistan. METHODS: This was a 26-week observational, multicenter,
      prospective, open-label study. At week 26, change from baseline in mean sitting
      systolic (msSBP) and diastolic blood pressure (msDBP) and the proportion of
      patients achieving BP goal (SBP/DBP <140/90 mmHg; <130/80 mmHg in patients with
      diabetes) and response rates (SBP <140 mmHg [130 mmHg for patients with diabetes]
      or reduction of >=20 mmHg; DBP <90 mmHg [80 mmHg for patients with diabetes] or
      reduction of >=10 mmHg), were evaluated. Incidence of adverse events (AEs) and
      serious AEs (SAEs) was recorded as safety variables. Subjective assessment of
      effectiveness, compliance and tolerability was done by the physician. RESULTS: A
      total of 500 patients with hypertension (mean age of 48 years) were prescribed
      Aml/Val (n = 471, 94%) or Aml/Val/HCTZ (n = 29, 6%); 439 (87.8%) patients
      completed the study. At week 26, the mean BP decreased from 153.4/91.1 mmHg at
      baseline to 128.9/78.4 mmHg in the Aml/Val cohort (-24.5/-12.7 mmHg; p < 0.0001)
      and from 171.6/99.3 mmHg at baseline to 127.7/77.4 mmHg (-43.9/-21.9 mmHg; p <
      0.0001) in the Aml/Val/HCTZ cohort. BP goals were achieved by 57% and 55.2% of
      patients in the Aml/Val and Aml/Val/HCTZ cohorts, respectively. A total of 40
      (8%) patients reported at least one AE during the study period. Most common AEs
      included nausea (1.6%), headache (1.2%), vomiting (1.2%), and edema (1.2%). Most
      patients in Aml/Val cohort and all patients in Aml/Val/HCTZ cohort rated the
      effectiveness, compliance and tolerability as 'good' or 'very good'. CONCLUSIONS:
      Aml/Val with or without HCTZ in a SPC was effective and well-tolerated for BP
      reduction in this cohort of patients with hypertension from Pakistan.

PMID- 24562477
TI  - A convenient preparation of N (epsilon)-methyl-L-lysine derivatives and its
      application to the synthesis of histone tail peptides.
AB  - A convenient route is established for the preparation of N (alpha)-Fmoc-N
      (epsilon)-(Boc, methyl)-L-lysine and N (alpha)-Fmoc-N (epsilon)-dimethyl-L-lysine
      as building blocks to be used for the synthesis of methylated peptides. This
      methodology is based on the use of malonate derivatives and dibromobutane to
      produce key intermediates, L-2-amino-6-bromohexanoic acid derivatives, which
      could be modified to the required group at the epsilon-position. Fmoc-protection
      is accessible, so these compounds can be used in solution as well as in solid
      phase peptide synthesis. Also the peptides containing these methylated lysines
      have been proved to resist the action of trypsin and lysyl endopeptidase. Thus,
      this new method could be considered as an improvement of the synthesis of N
      (epsilon)-methyl-L-lysine derivatives. 

PMID- 24562478
TI  - Solid-phase synthesis of amidine-substituted phenylbenzimidazoles and
      incorporation of this DNA binding and recognition motif into amino acid and
      peptide conjugates.
AB  - Amidine-substituted phenylbenzimidazoles are well-established DNA-binding
      structural motifs that have contributed to the development of diverse classes of
      DNA-targeted agents; this ring system not only assists in increasing the overall
      DNA affinity of an agent, but can also influence its site selectivity. Seeking a
      means to conveniently exploit these attributes, a protocol for the on-resin
      synthesis of amino acid- and peptide-phenylbenzimidazole-amidine conjugates was
      developed to facilitate installation of phenylbenzimidazole-amidines into peptide
      chains during the course of standard solid-phase syntheses. Building from a resin
      bound amino acid or peptide on Rink amide resin, 4-formyl benzoic acid was
      coupled to the resin-bound free amine followed by introduction of 3,4-diamino-N'
      hydroxybenzimidamide (in the presence of 1,4-benzoquinone) to construct the
      benzimidazole heterocycle. Finally, the resin-bound N'-hydroxybenzimidamide
      functionality was reduced to an amidine via 1 M SnCl2.2H2O in DMF prior to resin
      cleavage to release final product. This procedure permits the straightforward
      synthesis of amino acids or peptides that are N-terminally capped by a
      phenylbenzimidazole-amidine ring system. Employing this protocol, a series of
      amino acid-phenylbenzimidazole-amidine (Xaa-R) conjugates was synthesized as well
      as dipeptide conjugates of the general form Xaa-Gly-R (where R is the
      phenylbenzimidazole-amidine and Xaa is any amino acid).

PMID- 24562490
TI  - Progress in the study of negative symptoms.
AB  - A selective review of the negative symptoms of schizophrenia is an appropriate
      article to result from the festschrift honoring William T. Carpenter Jr, as he
      has made substantial contributions in this area. This review assesses progress in
      3 areas in which he has been an important investigator: the distinction between
      primary vs secondary negative symptoms; the appropriate design for treatment
      trials; and the nosology of negative symptoms. 

PMID- 24562491
TI  - Psychopathological mechanisms linking childhood traumatic experiences to risk of
      psychotic symptoms: analysis of a large, representative population-based sample.
AB  - BACKGROUND: Different psychological models of trauma-induced psychosis have been
      postulated, often based on the observation of "specific" associations between
      particular types of childhood trauma (CT) and particular psychotic symptoms or
      the co-occurrence of delusions and hallucinations. However, the actual
      specificity of these associations remains to be tested. METHODS: In 2 population
      based studies with comparable methodology (Netherlands Mental Health Survey and
      Incidence Study-1 [NEMESIS-1] and NEMESIS-2, N = 13 722), trained interviewers
      assessed CT, psychotic symptoms, and other psychopathology. Specificity of
      associations was assessed with mixed-effects regression models with multiple
      outcomes, a statistical method suitable to examine specificity of associations in
      case of multiple correlated outcomes. RESULTS: Associations with CT were strong
      and significant across the entire range of psychotic symptoms, without evidence
      for specificity in the relationship between particular trauma variables and
      particular psychotic experiences (PEs). Abuse and neglect were both associated
      with PEs (OR abuse: 2.12, P < .001; OR neglect: 1.96, P < .001), with no large or
      significant difference in effect size. Intention-to-harm experiences showed
      stronger associations with psychosis than CT without intent (chi(2) = 58.62, P <
      .001). Most trauma variables increased the likelihood of co-occurrence of
      delusions and hallucinations rather than either symptom in isolation. DISCUSSION:
      Intention to harm is the key component linking childhood traumatic experiences to
      psychosis, most likely characterized by co-occurrence of hallucinations and
      delusions, indicating buildup of psychotic intensification, rather than specific
      psychotic symptoms in isolation. No evidence was found to support psychological
      theories regarding specific associations between particular types of CT and
      particular psychotic symptoms.

PMID- 24562492
TI  - Bipolar and schizophrenia network for intermediate phenotypes: outcomes across
      the psychosis continuum.
AB  - Bipolar and schizophrenia network for intermediate phenotypes is a network of
      investigator-driven laboratories focused on developing phenotypes, genotypes, and
      biomarkers for psychosis. Over the last 5 years, the consortium has accomplished
      a dense phenotyping protocol using probands with a lifetime history of psychosis,
      their relatives, and healthy controls. This has established a library of
      biomarker information on individuals with schizophrenia, schizoaffective
      disorder, and bipolar disorder with psychosis. The founding goal of establishing
      disease biomarkers for current psychotic diagnoses has been poorly met, because
      the cognitive, electrophysiologic, eye movement, and brain imaging biomarkers did
      not regularly discriminate individuals with different DSM psychosis diagnoses. In
      future, we will use this biomarker information to establish a pathway to
      biomarker-based classification in psychoses. 

PMID- 24562493
TI  - Future in psychopathology research.
AB  - Psychopathology research has focused either on the analysis of the mental state
      in the here and now or on the synthesis of mental status abnormalities with
      biological markers and outcome data. These two schools of psychopathology, the
      analytic and the synthetic, make contrasting assumptions, take different
      approaches, and pursue divergent goals. Analytic psychopathology favors the
      individual person and unique biography, whereas synthetic psychopathology
      abstracts from the single case and generalizes to the population level. The
      dimension of time, especially the prediction of future outcomes, is viewed
      differently by these two schools. Here I outline how Carpenter's proposal of
      strong inference and theory testing in psychopathology research can be used to
      test the value of analytic and synthetic psychopathology. The emerging field of
      personalized psychiatry can clarify the relevance of psychopathology for
      contemporary research in psychiatry. 

PMID- 24562495
TI  - William T. Carpenter Jr: 35 years of clinical trials.
AB  - William T. Carpenter Jr has had a major impact on the design and conduct of
      clinical trials in schizophrenia. His contributions range from the decisive
      evaluation of the efficacy of hemodialysis to the development of novel approaches
      to evaluate new treatments for cognitive impairments and negative symptoms. He
      has developed innovative dosage reduction strategies. He has led efforts to focus
      drug development on those illness components that are not responsive to
      antipsychotic treatment. He has emphasized throughout his career the use of
      translational science to provide the conceptual framework for clinical trial
      interventions. This article reviews highlights of his many contributions, with an
      emphasis on 3 areas: (1) dosage reduction studies; (2) the use of the domains of
      psychopathology to identify drug development targets; and (3) the use of
      translational science to guide new drug development. 

PMID- 24562496
TI  - Celebrating the work of William T. Carpenter Jr.

PMID- 24562494
TI  - Targeting kynurenine aminotransferase II in psychiatric diseases: promising
      effects of an orally active enzyme inhibitor.
AB  - Increased brain levels of the tryptophan metabolite kynurenic acid (KYNA) have
      been linked to cognitive dysfunctions in schizophrenia and other psychiatric
      diseases. In the rat, local inhibition of kynurenine aminotransferase II (KAT
      II), the enzyme responsible for the neosynthesis of readily mobilizable KYNA in
      the brain, leads to a prompt reduction in extracellular KYNA levels, and
      secondarily induces an increase in extracellular glutamate, dopamine, and
      acetylcholine levels in several brain areas. Using microdialysis in
      unanesthetized, adult rats, we now show that the novel, systemically active KAT
      II inhibitor BFF-816, applied orally at 30 mg/kg in all experiments, mimics the
      effects of local enzyme inhibition. No tolerance was seen when animals were
      treated daily for 5 consecutive days. Behaviorally, daily injections of BFF-816
      significantly decreased escape latency in the Morris water maze, indicating
      improved performance in spatial and contextual memory. Thus, systemically applied
      BFF-816 constitutes an excellent tool for studying the neurobiology of KYNA and,
      in particular, for investigating the mechanisms linking KAT II inhibition to
      changes in glutamatergic, dopaminergic, and cholinergic function in brain
      physiology and pathology.

PMID- 24562500
TI  - Photosynthetic responses of Oryza sativa L. seedlings to cadmium stress:
      physiological, biochemical and ultrastructural analyses.
AB  - In the present study, photosynthetic responses induced by cadmium stress in
      chlorophyll biosynthesis, photochemical activities, the stability of thylakoid
      membranes chlorophyll-protein complexes and the chloroplast ultrastructure of the
      cereal crop Oryza sativa L. were characterized. Cadmium inhibited the
      biosynthesis of chlorophyll by interfering with activity of delta-aminolevulinic
      acid dehydratase in the rice seedlings. For the photochemical activities
      analyses, the extent of the decrease in photosystem II activity was much greater
      than that in the PS I activity. The variations in the chlorophyll a fluorescence
      parameters also indicated that cadmium toxicity drastically affected the
      photochemistry of PS II. Biochemical analyses by BN-PAGE and protein immunoblot
      showed that cadmium toxicity considerably affected the stability of PS II-core,
      cytb 6 /f, RuBisCO, PSI + LHCI and LHCII (Trimeric). We observed the rate of the
      thylakoid membranes protein degradation, was mainly at the level of RbcL, PsaA,
      Lhca1 and D1. In addition, the damages to chloroplast structure and thylakoid
      stacking analyzed by transmission electron microscopy were indicative of general
      disarray in the photosynthetic functions exerted by cadmium toxicity. These
      results are valuable for understanding the biological consequences of heavy
      metals contamination particularly in soils devoted to organic agriculture. 

PMID- 24562502
TI  - Photodissociation dynamics of propargylene, HCCCH.
AB  - We report a joint theoretical and experimental study on the photodissociation of
      the C3H2 isomer propargylene, HCCCH, combining velocity map imaging with
      nonadiabatic trajectory surface hopping calculations. Propargylene loses an H
      atom, after laser excitation at around 250 nm, presumably to the T6 state. The
      photofragment angular distribution exhibits only a very small anisotropy, but the
      H-atom translational energy distribution extends to high energies and shows an
      expectation value of <fT>, the fraction of excess energy released as translation,
      of 48%, outside the range expected for a statistical reaction mechanism. The
      computations suggest a predissociation in the T4-T6 state and lead to a
      translational energy distribution and photofragment angular distribution that
      match the experimentally observed ones very well. 

PMID- 24562503
TI  - Decreased expression of miR-146a and miR-155 contributes to an abnormal Treg
      phenotype in patients with rheumatoid arthritis.
AB  - OBJECTIVES: MicroRNAs (miRNAs) have been implicated in the pathogenesis of
      autoimmune diseases, not least for their critical role in the regulation of
      regulatory T cell (Treg) function. Deregulated expression of miR-146a and miR-155
      has been associated with rheumatoid arthritis (RA). We therefore investigated miR
      146a and miR-155 expression in Tregs of patients with RA and their possible
      impact on Treg function and disease activity. METHODS: Expression of miR-146a and
      miR-155 was assessed in RA patients and controls. MiRNA expression was correlated
      with disease activity and expression of target genes. Interference with
      biological activity of miRNAs was evaluated in functional Treg assays. RESULTS:
      Diminished upregulation of miR-146a and miR-155 in response to T cell stimulation
      was found in Tregs of RA patients. Diminution of miR-146a expression was observed
      in particular in patients with active disease, and correlated with joint
      inflammation. In patients with active RA, Tregs demonstrated a pro-inflammatory
      phenotype characterised by inflammatory cytokine expression. This was due to an
      augmented expression and activation of signal transducer and activator
      transcription 1 (STAT1), a direct target of miR-146a. CONCLUSIONS: Our results
      suggest that in RA miR-146a facilitates a pro-inflammatory phenotype of Tregs via
      increased STAT1 activation, and contributes thereby to RA pathogenesis.

PMID- 24562499
TI  - Stress, ageing and their influence on functional, cellular and molecular aspects
      of the immune system.
AB  - The immune response is essential for keeping an organism healthy and for
      defending it from different types of pathogens. It is a complex system that
      consists of a large number of components performing different functions. The
      adequate and controlled interaction between these components is necessary for a
      robust and strong immune response. There are, however, many factors that
      interfere with the way the immune response functions. Stress and ageing now
      consistently appear in the literature as factors that act upon the immune system
      in the way that is often damaging. This review focuses on the role of stress and
      ageing in altering the robustness of the immune response first separately, and
      then simultaneously, discussing the effects that emerge from their interplay. The
      special focus is on the psychological stress and the impact that it has at
      different levels, from the whole system to the individual molecules, resulting in
      consequences for physical health. 

PMID- 24562504
TI  - Postpartum intimate partner violence and health risks among young mothers in the
      United States: a prospective study.
AB  - The study assessed the relationship between postpartum intimate partner violence
      (IPV) and postpartum health risks among young mothers over time. Data were
      collected from 2001 to 2005 on young women aged 14-25 attending obstetrics and
      gynecology clinics in two US cities. Postpartum IPV (i.e., emotional, physical,
      sexual) was assessed at 6 and 12 months after childbirth (n = 734). Four types of
      postpartum IPV patterns were examined: emerged IPV, dissipated IPV, repeated IPV,
      and no IPV. Emerged IPV occurred at 12 months postpartum, not 6 months
      postpartum. Dissipated IPV occurred at 6 months postpartum, not 12 months
      postpartum. Repeated IPV was reported at 6 months and 12 months postpartum.
      Postpartum health risks studied at both time points were perceived stress,
      depression, fear of condom negotiation, condom use, infant sleeping problems, and
      parental stress. Repeated measures analysis of covariance was used. The
      proportion of young mothers reporting IPV after childbirth increased from 17.9 %
      at 6 months postpartum to 25.3 % at 12 months postpartum (P < 0.001). Emerged
      and/or repeated postpartum IPV were associated with increased perceived stress,
      depression, fear of condom negotiation, and infant sleeping problems as well as
      decreased condom use (P < 0.05). Dissipated postpartum IPV was associated with
      decreased depression (P < 0.05). IPV screening and prevention programs for young
      mothers may reduce health risks observed in this group during the postpartum
      period.

PMID- 24562505
TI  - Linkage methods for connecting children with parents in electronic health record
      and state public health insurance data.
AB  - The objective of this study was to develop methodologies for creating child
      parent 'links' in two healthcare-related data sources. We linked children and
      parents who were patients in a network of Oregon clinics with a shared electronic
      health record (EHR), using data that reported the child's emergency contact
      information or the 'guarantor' for the child's visits. We also linked children
      and parents enrolled in the Oregon Health Plan (OHP; Oregon's public health
      insurance programs), using administrative data; here, we defined a 'child' as
      aged <19 years and identified potential 'parents' from among adults sharing the
      same OHP household identification (ID) number. In both data sources, parents had
      to be 12-55 years older than the child. We used OHP individual client ID and EHR
      patient ID numbers to assess the quality of our linkages through cross
      validation. Of the 249,079 children in the EHR dataset, we identified 62,967 who
      had a 'linkable' parent with patient information in the EHR. In the OHP data,
      889,452 household IDs were assigned to at least one child; 525,578 with a
      household ID had a 'linkable' parent (272,578 households). Cross-validation of
      linkages revealed 99.8 % of EHR links validated in OHP data and 97.7 % of OHP
      links validated in EHR data. The ability to link children and their parents in
      healthcare-related datasets will be useful to inform efforts to improve
      children's health. Thus, we developed strategies for linking children with their
      parents in an EHR and a public health insurance administrative dataset.

PMID- 24562506
TI  - Soft tissue perineurioma of the foot with 10q24 rearrangements: unique MRI
      features with histopathologic correlation.
AB  - Perineurioma is an uncommon benign peripheral nerve sheath tumor with advanced
      perineurial differentiation. Two distinct subtypes are recognized: intraneural
      and soft tissue. We herein present a unique case of soft tissue perineurioma in
      the right foot of a 43-year-old man. Radiographs showed a non-specific soft
      tissue mass. On computed tomography scan, the mass was iso- to slightly hypodense
      relative to muscle. On T1- and T2-weighted images, the mass exhibited iso- to
      slightly low signal intensity relative to muscle with foci of high signal
      intensity. Slight contrast enhancement was noted on enhanced T1-weighted images
      with fat suppression. A marginal excision of the tumor was performed and
      histopathologic examination confirmed the diagnosis of soft tissue perineurioma.
      The clinicopathologic, radiologic, and cytogenetic findings are described, and
      the relevant literature is reviewed. 

PMID- 24562509
TI  - Catamenial pneumothorax. Is it time to approach differently?
AB  - Catamenial pneumothorax CP was considered a rare clinical entity that has gained
      tremendous interest recently. It is commonly overlooked, misdiagnosed, or under
      diagnosed. It is part of the thoracic endometriosis syndrome, which includes
      catamenial hemothorax, catamenial hemoptysis, and pulmonary endometriosis. These
      represent the spectrum of ectopic pelvic endometriosis. The presentation is
      variable leading to difficulty in developing a standardized approach to diagnosis
      and management. This review discusses the pathogenesis of these entities and the
      novel methods of investigation, management, and clinical protocols. 

PMID- 24562508
TI  - Targeted transtracheal stimulation for vocal fold closure.
AB  - Paralysis of the structures in the head and neck due to stroke or other
      neurological disorder often causes dysphagia (difficulty in swallowing). Patients
      with dysphagia have a significantly higher incidence of aspiration pneumonia and
      death. The recurrent laryngeal nerve (RLN), which innervates the intrinsic
      laryngeal muscles that control the vocal folds, travels superiorly in parallel to
      the trachea in the tracheoesophageal groove. This study tests the hypothesis that
      functional electrical stimulation (FES) applied via transtracheal electrodes can
      produce controlled vocal fold adduction. Bipolar electrodes were placed at 15
      degrees  intervals around the interior mucosal surface of the canine trachea, and
      current was applied to the tissue while electromyography (EMG) from the intrinsic
      laryngeal muscles and vocal fold movement visualization via laryngoscopy were
      recorded. The lowest EMG thresholds were found at an average location of 100
      degrees  to the left of the ventral midsagittal line and 128 degrees  to the
      right. A rotatable pair of bipolar electrodes spaced 230 degrees  apart were able
      to stimulate bilaterally both RLNs in every subject. Laryngoscopy showed complete
      glottal closure with transtracheal stimulation in six of the eight subjects, and
      this closure was maintained under simultaneous FES-induced laryngeal elevation.
      Transtracheal stimulation is an effective tool for minimally invasive application
      of FES to induce vocal fold adduction, providing an alternative mechanism to
      study airway protection. 

PMID- 24562507
TI  - Physiological factors related to aspiration risk: a systematic review.
AB  - Penetration-aspiration is considered the most serious component of oropharyngeal
      dysphagia. Clinicians regularly evaluate the pathophysiology of swallowing and
      postulate reasons or mechanisms behind penetration-aspiration. In this article we
      share the results of a two-stage literature review designed to elucidate the
      association between abnormalities in physiological measures of swallowing
      function and the occurrence of penetration-aspiration. In the first stage, a
      broad scoping review was undertaken using search terms for nine different
      structures involved in oropharyngeal swallowing. In the second stage, based on
      the results of the initial search, a more focused systematic review was
      undertaken which explored the association between aspiration and abnormalities in
      respiratory, tongue, hyoid, and laryngeal function in swallowing. A total of 37
      articles underwent detailed quality review and data extraction in the systematic
      review. The results support measurement of tongue strength, anatomically
      normalized measures of hyoid movement, bolus dwell time in the pharynx while the
      larynx remains open, respiratory rate, and respiratory swallow phasing as
      parameters relevant to aspiration risk. 

PMID- 24562510
TI  - Chloral hydrate versus midazolam as sedative agents for diagnostic procedures in
      children.
AB  - OBJECTIVE: To compare sedation outcomes for chloral hydrate (CH) and midazolam
      (MD) as sedative agents for diagnostic procedures in children. METHODS: A
      prospective, randomized, double-blinded study conducted between July 2005 and
      October 2006, at the Pediatric Day Care Unit (DCU), King Abdulaziz Medical City,
      Riyadh, Saudi Arabia. After meeting the inclusion criteria and getting informed
      consent, patients were randomized, given the study drug, and monitored for
      sedation outcomes. RESULTS: Two hundred and seventy-five patients who had 292
      sedation sessions for diagnostic procedures were included in the study. Due to
      missing data, 286 sedations were included in the final analysis; 144 in the CH
      and 142 in the MD group. Both groups were comparable with respect to demographic
      and baseline characteristics. The CH compared to MD group, had a higher sedation
      success rate, shorter time to achieve sedation, shorter length of stay in DCU,
      and longer sedation duration. In both study groups, patients who required a
      second dose tended to be older and heavier. No major side effects were
      encountered. The CH group had a significantly higher mean sedation scores at 15,
      30, 45, and 60 minutes. CONCLUSION: Chloral hydrate compared to MD, had a shorter
      time to achieve sedation, a higher success rate, less need for a second dose, and
      decreased the time spent in the DCU. Older and heavier patients are more likely
      to require a second dose of the study drug to be sedated.

PMID- 24562511
TI  - Association of plasma glucose, insulin, and cardiovascular risk factors in
      overweight and obese children.
AB  - OBJECTIVE: To investigate the association between fasting plasma glucose (FPG), 2
      hour post challenge plasma glucose (2hPG), fasting plasma insulin (FINS), 2-hour
      post challenge plasma insulin (2hINS), and cardiovascular risk factors in obese
      and overweight children. METHODS: This is a cross-sectional study of 452 obese
      and overweight children (male: 312, female: 140, aged 6-16 years). This study was
      conducted in the Department of Pediatrics, General Hospital of Tianjin Medical
      University, Tianjin, China between June 2008 and November 2012. Anthropometries
      and blood analysis were carried out. Pearson correlation analysis and multiple
      stepwise linear regression analysis were used to investigate the association
      among FPG, 2hPG, FINS, 2hINS and cardiovascular risk factors. RESULTS: Body mass
      index, waist circumference, waist to hip ratio, systolic blood pressure,
      diastolic blood pressure, and triglyceride were highly correlated with FINS.
      Fasting plasma insulin influenced greater variance in most cardiovascular risk
      factors than 2hPG and 2hINS. CONCLUSION: Fasting plasma insulin was closely
      associated with most cardiovascular risk factors compared with FPG, 2hPG and
      2hINS.

PMID- 24562512
TI  - Augmentation index is a better marker for cardiovascular risk in young Malaysian
      males. A comparison of involvement of pulse wave velocity, augmentation index,
      and C-reactive protein.
AB  - OBJECTIVE: To determine the association between carotid femoral pulse wave
      velocity (PWVCF) and augmentation index (AI) with future cardiovascular disease
      (CVD) risk, and to assess whether high sensitivity C-reactive protein (hs-CRP) is
      an important mediator towards these vascular changes, among young men. METHODS:
      This cross-sectional study was conducted at Universiti Kebangsaan Malaysia
      Medical Center, Kuala Lumpur, Malaysia from July 2011 to December 2012. Two
      hundred and eleven young men were recruited. The PWVCF and AI were measured using
      Vicorder. High sensitivity C-reactive protein was measured by using immunological
      methods. The future CVD risk was assessed by Framingham risk score (FRS) and age
      adjusted FRS (A-FRS). Data for analysis was conducted using the Statistical
      Package for Social Sciences Version 15 (SPSS Inc., Chicago, IL, USA). RESULTS:
      The mean age of the subjects was 27.09 (95% confidence intervals [CI] 26.39
      27.79) years old. Those with >=2 risk factors had significantly higher AI [10.09
      (95% CI: 9.06-11.12) versus 6.56 (95% CI: 5.54-7.57) (p=0.001), but not PWVCF
      7.45 (95% CI: 7.29-7.61) m/s versus 7.29 (95% CI: 7.06-7.51) m/s, (p=0.90) when
      compared to the healthy subjects. High sensitivity C-reactive protein was not an
      independent determinant for PWVCF and AI. Only AI was significantly associated
      with FRS and A-FRS (p=0.0001). CONCLUSION: To assess the impact of risk factors
      on vascular damage and for future assessment of CVD risk among the young men, AI
      may be a better marker than PWVCF. The increase in AI among these subjects was
      not related to hs-CRP.

PMID- 24562513
TI  - Determinants of hand hygiene non-compliance in a cardiac center in Saudi Arabia.
AB  - OBJECTIVE: To evaluate the baseline hand hygiene non-compliance rate, and
      identify the factors associated with non-compliance in a cardiac center in Saudi
      Arabia. METHODS: This observational study was conducted in Prince Sultan Cardiac
      Center, Riyadh, Saudi Arabia, a 176 beds specialized cardiac center. In total,
      6,022 observations were recorded by using the Infection Control Link Nurse
      program from all the high and non-high risk areas from October to December 2012.
      The data was collected from different healthcare workers (HCW) for World Health
      Organization 5 indications of hand hygiene. Non-compliance rate was calculated,
      and univariate and multivariate analysis was performed using logistic regression
      to identify factors significantly associated with non-compliance. RESULTS: The
      overall hand hygiene non-compliance rate was observed to be approximately 34%.
      Factors significantly associated with non-compliance included physicians
      (OR=2.71, 95% confidence intervals [CI]=2.33-3.13), after touching the patient's
      surrounding (OR=4.8, 95% CI=3.98-5.78), before touching a patient (OR=3.3, 95%
      CI=2.87-3.86), and high-risk areas (OR=1.16, 95% CI=1.03-1.31). Morning shifts
      were significantly associated (OR=1.13, 95% CI=1.00-1.29) with non-compliance as
      compared to the evening shifts. CONCLUSION: Stratified analysis indicated that
      non-compliance is still a noticeable concern. The results suggest that broad
      spectrum educational activities and behavioral modification strategies should be
      advocated to include all HCW, particularly physicians, and should emphasize on
      performing hand hygiene during all the indications and not just the 'after'
      indications.

PMID- 24562514
TI  - Antibiotics exposure, risk factors, and outcomes with Candida albicans and non
      Candida albicans candidemia. Results from a multi-center study.
AB  - OBJECTIVE: To define the differences in antibiotics exposure, risk factors, and
      outcome in hospitalized patients with Candida albicans (C. albicans) and non-C.
      albicans candidemia. METHODS: This is a multi-center retrospective study of 132
      patients with candidemia from 5 tertiary-care educational hospitals in Shandong,
      China conducted between January 2009 and June 2010. Fifty-six of 132 (42.4%)
      patients had candidemia due to C. albicans and 76/132 (57.6%) had non-C.
      albanians candidemia. RESULTS: Patients with non-C. albicans candidemia received
      anti-anaerobic agents more often (23.7% versus 8.9%; p=0.027) and beta
      lactam/beta-lactamase inhibitors less often (34.2% versus 51.8%; p=0.043) than
      those with C. albicans candidemia. Independent risk factors of non-C. albicans
      candidemia were prior anti-anaerobic and antifungal therapies and central venous
      catheter placement. Overall, 30-day mortality was higher for patients with C.
      albicans than non-C. albicans candidemia (50% versus 31.6%; p=0.032).
      Multivariate logistic regression analysis revealed that C. albicans candidemia,
      advanced age, and concomitant bacteremia were associated with death due to
      candidemia. CONCLUSION: Patients who received anti-anaerobic or antifungal agents
      were likely to develop non-C. albicans candidemia. Candida albicans infection was
      associated with poorer prognosis. An awareness of these factors is needed to
      guide therapy and decrease the high mortality of candidemia.

PMID- 24562515
TI  - Potential risk factors for patient mortality during admission to the intensive
      care units.
AB  - OBJECTIVE: To determine the prognostic importance of admission time, admission
      day, admission source, and route of admission, attached devices before admission,
      diagnosis of patients, and total Simplified Acute Physiology Score (SAPS) II
      score during admission on intensive care unit mortality rates. METHODS: This
      retrospective study was carried out with 545 patients admitted to adult intensive
      care units between January 2006 and January 2011 at Zonguldak, Turkey.
      Computerised database and patient records were used for data collection. Data
      from the patient records was collected by a constructed survey form and SAPS II
      scale. The data was evaluated by numeric values and percentages, Pearson
      correlation analysis, logistic regression analysis, Chi-square, and student t
      tests. RESULTS: The mortality rate was 60.4%. The patients who died had a higher
      SAPS II score. The mortality rate was higher in admissions from the emergency
      department (p=0.000), admissions of patients on a stretcher (p=0.000), the
      existence of an intubation tube (p=0.000) and monitor (p=0.001), and in patients
      with respiratory tract illness (p=0.000), and infection (p=0.000). A significant
      difference was not found between the admission day (p=0.761), and time (p=0.063).
      CONCLUSION: The SAPS II scores of the patients, the route of admission and
      admission source, being intubated and connected to a monitor, admission
      diagnosis, and length of stay in intensive care units was increased to mortality
      rate. However, the days and hours of admission did not significantly affect
      mortality.

PMID- 24562516
TI  - Selective beta-1 blockers deteriorate glucose metabolism. A meta-analysis.
AB  - OBJECTIVE: To provide an up-to-date synthesis of available data, and to quantify
      the effect of highly selective beta-1 blockers on glucose metabolism in patients
      with essential hypertension and type diabetes mellitus (T2DM) by using pooled
      analysis techniques. METHODS: Cochrane Library, PubMed, MEDLINE, and EMBASE
      databases were searched from inception to July 2013 in the Third Affiliated
      Hospital of Nanchang University, Nanchang, China. We collected randomized
      controlled trails reporting on the effect of highly selective beta-1 blockers on
      glucose metabolism in patients with hypertension and type 2 diabetes. Data was
      screened, evaluated, and extracted by 2 independent researchers according to the
      inclusion and exclusion criteria. Meta-analysis was conducted using RevMan5.0
      software. RESULTS: Seven trials were enrolled in the meta-analysis including a
      total of 1354 patients. Meta-analysis results revealed that when compared with
      the control group, selective beta-1 blockers were associated with a higher
      fasting blood glucose (weighed mean difference: 0.21, 95% confidence interval
      [CI]: 0.16-0.27; p<0.00001). But results revealed no significant difference in
      glycosylated hemoglobin (weighed mean difference: 0.13, 95% CI: -0.11 to 0.37;
      p=0.28), fasting insulin (weighed mean difference: -1.13, 95% CI: -4.27 to 2.01;
      p=0.48), and gain in body weight (weighed mean difference: 1, 95% CI: -1.08 to
      3.08; p=0.35). CONCLUSION: Selective beta-1 blockers were associated with
      elevated fasting blood glucose. Thus, it should not be used for patients with
      essential hypertension and diabetes.

PMID- 24562517
TI  - Administered antipsychotic pro re nata medications in psychiatric inpatients. Pre
      and post-accreditation comparison.
AB  - OBJECTIVE: To investigate whether the mental health accreditation program drives
      improvements in the clinical practice of giving pro re nata (PRN) antipsychotic
      medications for psychiatric inpatients. METHODS: This study was conducted in
      October 2012, a record-based pre-post assessment design in psychiatric inpatient
      wards at King Khalid University Hospital, Riyadh, Saudi Arabia. Data collected
      from a 12-month pre-accreditation period (July 2009 to June 2010) was compared
      with those from a 12-month post-accreditation period (July 2011 to June 2012).
      The collected data identified demographics, diagnosis, number of PRN
      antipsychotic medications administered per patient, and indications for use.
      RESULTS: There were 177 patients during the pre-accreditation period, and 182
      patients during the post-accreditation period. Before accreditation, 87% of
      patients were administered PRN antipsychotics and the average number of PRN
      antipsychotic administrations per patient was 12.10+/-7.0 compared with 81% of
      patients being administered 7.47+/-3.2 PRN antipsychotic medications per patient
      post-accreditation. Prior to accreditation, a high number of PRN antipsychotic
      medications were administered to patients with no specified indications
      (rs=0.698; p<0.001). During the post-accreditation period, the corresponding
      correlation coefficients significantly declined to rs=0.465; p<0.001. CONCLUSION:
      Implementation of clinical practice guidelines in psychiatric inpatients
      significantly reduces the frequency of PRN antipsychotic medications and enhances
      patient safety.

PMID- 24562518
TI  - Prevalence of vitamin D deficiency in Saudi newborns at a tertiary care center.
AB  - OBJECTIVE: To evaluate vitamin D levels in Saudi newborns utilizing umbilical
      cord samples, and to benchmark the results with international figures. METHODS:
      This cross-sectional study was carried out at King Khalid University Hospital,
      Riyadh, Saudi Arabia between November 2013 and March 2013. Vitamin D levels were
      assessed in the umbilical cord of healthy term neonates born above 2.5 kg from
      healthy pregnant mothers. Gestational age (GA), birth weight, gender, levels of
      sun exposure, and consumption of vitamin D rich food data were collected. Our
      primary outcome was the percentage of newborns with vitamin D deficiency (vitamin
      D level below 25 nmol/l). Association of vitamin D deficiency with sun exposure
      and consumption of vitamin D rich food was tested using a Chi-squared test.
      RESULTS: Umbilical samples of 200 newborns were obtained. The average birth
      weight was 3.2 kg. Deficient vitamin D levels were detected in 59% of the sample.
      Almost 90% of included newborns had vitamin D levels below 50 nmol/l. We found no
      association of vitamin D deficiency status to level of sun exposure or to
      consumption of vitamin D rich food. CONCLUSION: Vitamin D deficiency is very
      common in Saudi newborns at hospital, and is consistent with regional data.
      Efforts to assess and treat vitamin D deficiency during pregnancy and provide
      adequate supplementation to newborns are necessary to rectify such a public
      health concern.

PMID- 24562519
TI  - Perceptions of Saudi medical students on the qualities of effective teachers. A
      cross sectional study.
AB  - OBJECTIVE: To identify the attributes of an effective medical teacher that
      students value the most. METHODS: A quantitative survey was performed in the
      College of Medicine, Qassim University, Buraidah, Kingdom of Saudi Arabia,
      between April and May 2012, using a pretested self-administered questionnaire
      distributed to all students. It captured their opinions on the qualities and
      attributes of good teachers. Each item was measured on a 5-point Likert scale.
      Data were entered and analyzed using the Statistical Package for Social Sciences
      Version 17. RESULTS: Three hundred and fifty-six students from all years
      responded. The most important attributes from the students' perspectives were
      "respectful to students", "expert on the subject", "organizes good lectures",
      "understands/relates to students", and "good communication skills". On the other
      hand, "good sense of humor", "explains and shares personal experiences", "self
      sacrificing", "gives good marks to all students", and "dresses up appropriately"
      were least valued by students. Attributes related to performance were valued more
      by students compared to personality attributes. CONCLUSION: Medical teachers and
      administrators should focus on improving the attributes identified most important
      to the students. Future studies could define the important attributes more
      explicitly.

PMID- 24562521
TI  - Iatrogenic water intoxication in healthy parturient causing convulsions and
      fractured mandible.
AB  - We report a case of a mandibular dentoalveolar fracture caused by severe
      iatrogenic hyponatremia-induced grand mal seizure in a 31-year-old pregnant lady
      who underwent normal vaginal delivery. She had oxytocin augmentation of her
      labor, and the seizure happened in the immediate postpartum period. The seizure
      was thought to be because of severe hyponatremia and prompt management controlled
      the metabolic disorder. The fracture was reduced and fixed successfully, and she
      was discharged after 48 hours, healing was uneventful. 

PMID- 24562522
TI  - Pycnogenol(r) supplementation and its beneficial effects in healthy rats.

PMID- 24562520
TI  - An unusual case of bezoar from Sudan.
AB  - Pica is an abnormal eating behavior in which patients persistently eat non-food
      materials, which can lead to health consequences. A man presented complaining of
      several months of back pain and constipation without vomiting, abdominal pain, or
      distension. He experienced increasing social isolation and emotional lability
      over 5 years. Radiological findings confirmed the diagnosis, noting multiple
      radiopaque foreign bodies. Several types of pica are described based on the
      substance consumed. Bezoars may develop in the gastrointestinal tract as a result
      of these ingestions. Lithobezoars are rare types of bezoars, more common in males
      and psychiatric patients. An important clue to the diagnosis of lithobezoars is
      severe constipation, recurrent abdominal or back pain, and painful defecation.
      The diagnosis might not be made for years if such symptoms are not related to
      careful history, abdominal examination, or radiological findings. 

PMID- 24562523
TI  - Spectrum and antimicrobial resistance of uropathogens from patients with urinary
      tract infection in urology and non-urology departments.

PMID- 24562524
TI  - Menetrier's disease in a Saudi child.

PMID- 24562525
TI  - A prospective phase II trial of S-1 and cisplatin-based chemoradiotherapy for
      locoregionally advanced esophageal cancer.
AB  - PURPOSE: S-1 is a novel oral fluoropyrimidine anticancer agent designed to
      enhance clinical efficacy, reduce gastrointestinal toxicity, and enhance
      radiotherapy effectiveness. A phase II trial was conducted to evaluate the
      efficacy and safety of preoperative chemoradiation with S-1 and cisplatin in
      locoregionally advanced esophageal cancer. METHODS: Eligible patients had stage
      IIA-IVA esophageal cancer. Patients received two cycles of S-1 (days 1-14 and
      days 22-35) and cisplatin (days 1 and 22) with concurrent radiotherapy (50.4 Gy
      total; 1.8 Gy/fraction). Esophagectomy was performed between weeks 12 and 18 as
      determined by the specialist multidisciplinary team. RESULTS: Sixty patients were
      enrolled in this study between March 2008 and August 2011, and 59 were eligible.
      The clinical stage was >=T3 in 28 patients (47 %) and N1 in 43 patients (72 %),
      with squamous cell carcinoma histology in 58 patients (97 %). Fifty-four patients
      (90 %) completed the planned chemoradiation. After chemoradiation, the clinical
      tumor response rate was 64.4 %. The primary toxicities included neutropenia (24
      %) and esophagitis (8.5 %). Three treatment-related deaths were noted. Twenty
      five patients (42 %) underwent esophagectomy following chemoradiation, and 15
      achieved complete pathologic regression. The estimated overall survival and
      progression-free survival rates after 2 years were 65 and 48 %, respectively.
      CONCLUSIONS: Concurrent chemoradiation with S-1 and cisplatin exhibited
      encouraging results with complete pathologic regression. The survival data were
      promising compared with the historical data of 5FU/cisplatin and should be
      confirmed in a randomized phase III trial. Toxicities were significant but
      clinically manageable.

PMID- 24562526
TI  - Perception and needs of reproductive specialists with regard to fertility
      preservation of young breast cancer patients.
AB  - BACKGROUND: Treatment-related infertility is one of the important quality-of-life
      issues in young breast cancer (YBC) patients. Although existing guidelines
      recommend supporting fertility preservation (FP) of YBC, the perceptions of
      reproductive specialists (RS) has not been evaluated. We investigated the
      perceptions and needs of RS with regard to FP of YBC patients. METHODS: A cross
      sectional survey was sent to 423 certified RS registered to the Japan Society for
      Reproductive Medicine to self-evaluate their perceptions and needs regarding FP
      in YBC patients. RESULTS: Two hundred RS (47 %) responded to the survey. 99 %
      responded that RS should be engaged in FP of YBC patients. 88 % responded that
      they would like to treat YBC patients, while 46 % responded that cancer treatment
      is more important than childbirth, even when the patient is recurrence-free 5
      years after primary treatment. Respondents affiliated to private clinics were
      more likely to accept both fertilized and unfertilized egg preservation than
      those affiliated with academic or general hospitals. 70 % responded that they
      were anxious about treating breast cancer patients: concerns regarding a greater
      or unknown risk of recurrence (66 %), insufficient knowledge about breast cancer
      (47 %), and lack of a patient's spouse/partner (24 %) were identified as major
      barriers in supporting FP for YBC patients. CONCLUSIONS: RS recognize the need
      for FP in YBC patients and are willing to participate in their care. Affiliation
      of RS was related to a positive attitude to egg preservation. Various concerns
      regarding FP among RS indicate the need for evidence that supports the safety of
      FP, inter-disciplinary communication, and practice guidelines.

PMID- 24562527
TI  - Endocellular regulation by free radicals and hydrogen peroxide: key determinants
      of the inflammatory response.
AB  - The formations of reactive oxygen species (ROS) and reactive nitrogen species
      (RNS) have long been considered as major contributors to the dysregulation of the
      inflammatory response. Reactive oxygen species and RNS productions often are
      reported to be associated with the development of chronic diseases and
      acceleration of the aging process. Mechanistically, this association has linked
      the phenomena of oxidative stress with the occurrence of random deleterious
      modifications of macromolecules with progressive development of pro-inflammatory
      conditions promoting age-associated systemic diseases. On the contrary the so
      called random modification of macromolecules is incorrect rather ROS and RNS are
      molecular regulators (second messengers) and not universal toxins whose
      overproduction should be annulled by antioxidants. We have previously reviewed
      the physiological role of superoxide anion (and hydrogen peroxide) and nitric
      oxide (and peroxynitrite) and concluded that these reactive molecular species
      behave as pro-oxidant second messengers. Reactive oxygen species and RNS are
      produced at specific cellular locations and are essential for both the normal
      physiological function of the metabolome and the regulated inflammatory response.
      This brings into question the whole concept of the orally administering of
      antioxidant molecular species to down-regulate or abrogate an overproduction of
      free radical activity. There are no human clinical trials that demonstrate that
      small molecules, the so-called antioxidants (e.g., vitamins C, vitamin E and beta
      carotene), confer a favorable clinical outcome of long-lasting control of
      inflammation. 

PMID- 24562539
TI  - West nile virus infections in children.
AB  - West Nile virus, a flavivirus identified in Africa in the 1930s, appeared in the
      Western Hemisphere in 1999. Since its appearance, West Nile virus has caused
      nearly 40,000 cases of human disease in the US and more than 1,500 deaths, mostly
      among elderly persons with neuroinvasive disease. This review summarizes recent
      information regarding the clinical manifestations and prevention of West Nile
      virus infections in children, and emphasizes that although West Nile virus fever
      and neuroinvasive disease primarily affect adults, infants and children remain at
      risk of serious complications, including death, from this disorder. 

PMID- 24562540
TI  - How Might We Cure HIV?
AB  - Antiretroviral therapy (ART) does not eliminate HIV-1 from latently infected
      reservoirs, and this remains the critical obstacle to the eradication of
      infection. Although ART is effective in suppressing viral load, life-long ART is
      burdensome in many respects. Given expanding numbers of HIV-infected individuals
      on ART worldwide, there is an urgent need to examine the possibility that
      innovative therapies might eradicate infection, and obviate the need for life
      long medical therapy for HIV-positive people around the world. Several approaches
      to eradicating the latent HIV reservoir and curing infection have been proposed
      and are under study. An initial strategy seeks to induce the expression of the
      latent integrated proviral genomes within resting CD4+ T cells, so that viral
      proteins or particles may be revealed and allow these cellular reservoirs to be
      cleared. The inducing agents that have been studied recently are inhibitors of
      histone deacetylase (HDAC) such as suberoylanilide hydroxamic acid (SAHA). Such
      induction of viral expression seems unlikely in itself to efficiently clear all
      latently infected cells. Therefore, it seems likely that parallel efforts to
      augment the HIV-specific immune response with specific immunotherapies or
      vaccination may be required. Recently, efforts to achieve immune augmentation by
      ex vivo expansion of viral specific cytotoxic T-cell lymphocytes derived from HIV
      infected patients have yielded an augmented HIV-specific immune response in vivo,
      as have cellular vaccinations delivered by administration of dendritic cells. As
      HIV latency and the persistence of infection despite effective ART is
      multifactorial, the eradication of HIV infection may require multiple approaches.

PMID- 24562541
TI  - Rabies in travelers.
AB  - Most cases of rabies in travelers are associated with dog bites and occur in
      adults who are commonly migrants. The incidence of injuries to travelers caused
      by potentially rabid animals is approximately 0.4 % per month of stay. Dogs
      account for 51 % of cases, but nonhuman primates are the leading animals
      responsible for injuries in travelers returning from Southeast Asia. Travel to
      Southeast Asia, India and North Africa, young age, and traveling for tourism are
      risk factors for potential exposure. More than 70 % of travelers are not
      immunized prior to departing and do not receive adequate care when injured. The
      intradermal vaccination route has been proven economical, safe and immunogenic in
      travelers. The immunity provided by the three-dose series is long-lasting and
      should be considered an investment for future travel. Abbreviated schedules may
      be used for last-minute travelers. 

PMID- 24562543
TI  - A combined approach to predict spatial temperature evolution and its consequences
      during FIB processing of soft matter.
AB  - Accessing local temperatures and their evolution during focused ion beam (FIB)
      processing is of particular importance in the context of polymers or biomaterials
      as they tend to undergo severe chemical and morphological damage due to the high
      temperatures arising. In this study we present a combination of ion trajectory
      simulations and thermal spike model based calculations, which allows predicting
      local temperatures, lateral distributions and evolution during FIB patterning.
      Simulations and calculations have been done without any approximation or
      correction factors and lead to results in very good agreement with experiments on
      polymers taking into account their thermal behaviour. Finally, the model is
      applied to different scanning strategies which demonstrate how classically
      applied patterning strategies lead to massive temperature increases which can be
      the knock out criteria for low melting materials. 

PMID- 24562542
TI  - Community-Acquired Pneumonia in HIV-Infected Individuals.
AB  - Community-acquired pneumonia continues to be an important complication of HIV
      infection. Rates of pneumonia decrease with the use of antiretroviral therapy but
      continue to be higher than in HIV uninfected individuals. Risk factors for
      pneumonia include low blood CD4+ count, unsuppressed plasma HIV load, smoking,
      injection drug use and renal impairment. Immunization against Streptococcus
      pneumoniae and smoking cessation can reduce this risk. It is unclear whether
      newly reported viral respiratory pathogens (such as the Middle East respiratory
      syndrome coronavirus, will be more of a problem in HIV-infected individuals than
      the general population. 

PMID- 24562544
TI  - Proteome analysis of hepatic non-parenchymal cells of immune liver fibrosis rats.
AB  - Elucidation of the mechanisms of liver fibrogenesis is important to treat liver
      fibrosis. In this study, we established rat models of liver fibrosis with stages
      from 0-1, 2, and 3-4 to 4 at 2, 4, 6, and 8 weeks, respectively, by injection of
      pig serum. Liver fibrogenesis was detected by Masson's trichrome staining. Rat
      non-parenchymal cells (NPCs) were enriched 4-fold by Percoll density gradient
      centrifugation. Protein extracts from NPCs were prepared at 4 and 8 weeks,
      separated by two-dimensional electrophoresis, and then stained with Coomassie
      Blue G-250. At 4 weeks, we identified 18 non-redundant differentially expressed
      proteins of which protein disulfide-isomerase associated protein 3 (PDIA3) and
      NDUV showed consistent expression at protein and mRNA levels from 4 to 8 weeks.
      PDIA3 was found to be down-regulated by Western blotting in the rat model and
      immunohistochemically in human liver. Our results revealed important aspects of
      the pathogenesis/progression of liver fibrosis and demonstrated important changes
      in protein expression levels of NPCs at various stages of liver fibrosis. 

PMID- 24562545
TI  - Are there any functional differences of the enteric nervous system between the
      right-sided diverticular colon and the left-sided diverticular colon? An in vitro
      study.
AB  - PURPOSE: To evaluate functional differences of the enteric nervous system (ENS)
      in patients between right-side colonic diverticula (RCD) and left-sided colonic
      diverticula (LCD), the author compared the ENS responses between RCD and LCD.
      METHODS: Ten specimens were obtained from 10 patients with RCD, and 16 specimens
      were taken from 16 LCD. As a control, twenty-two specimens of right-sided normal
      colon (RNC) were obtained from 22 colonic cancers. Twenty-four specimens of left
      sided normal colon (LNC) were obtained from 24 colonic cancers. A mechanography
      was used to evaluate in vitro muscle responses to electrical field stimulation
      (EFS) before and after treatment with various autonomic nerve blockers. RESULTS:
      Before blockade of the adrenergic and cholinergic nerves, the incidences of
      contraction via cholinergic nerve in the colons with diverticula were
      significantly greater than those in the normal colons (right-sided colon; p =
      0.0022, left-sided colon; p < 0.0001). There were no significant differences
      between RNC and LNC (p = 0.3606), and between RCD and LCD (p = 0.7684). After the
      blockade of adrenergic and cholinergic nerves, the incidence of relaxation via
      non-adrenergic non-cholinergic inhibitory (NANC) nerve in the normal colons was
      significantly greater than that in the diverticular colons (right-sided colon; p
      = 0.0435, left-sided colon; p = 0.0034). There were no significant differences
      between RNC and LNC (p = 0.2909) and between RCD and LCD (p = 0.9464).
      CONCLUSION: Cholinergic nerves were dominant in bilateral diverticular colon
      compared with bilateral normal colon. NANC inhibitory nerves were dominant in
      bilateral normal colon compared with bilateral diverticular colon. There were
      also no functional differences of the ENS between RCD and LCD.

PMID- 24562546
TI  - Clinical outcomes of robot-assisted intersphincteric resection for low rectal
      cancer: comparison with conventional laparoscopy and multifactorial analysis of
      the learning curve for robotic surgery.
AB  - BACKGROUND: This study evaluated the feasibility of robot-assisted
      intersphincteric resection (ISR) for low rectal cancer. Further, we attempted to
      analyze the learning curve for robotic surgery. METHODS: A total of 64 patients
      were retrospectively chart-reviewed. Patients were classified into a laparoscopic
      procedure (n = 28) group and a robot-assisted (n = 36) group. Comparisons of age,
      gender, clinical staging, operating time, complications, and pathologic status
      were analyzed. Besides, we used a seventh-order moving average method for the
      construction of a learning curve in robotic surgery. RESULTS: Operating time was
      374.3 min (range, 210-570 min) in the laparoscopic group and 485.8 min (range,
      315-720 min) in the robotic group, with statistical difference between these two
      groups (P < 0.001). Thirteen patients (46.4 %) received diverting stoma in the
      laparoscopic group and seven patients (19.4 %) in the robotic group, with
      statistical difference between these two groups (P = 0.021). Operative experience
      of robotic ISR showed that the mean operating time was 519.5 min (range, 360-720
      min) in the first stage and 448.2 min (range, 315-585 min) in the second stage,
      with statistical difference between these two stages (P = 0.02). Multifactorial
      analysis showed that protective diverting stoma creation or neorectum necrosis
      was not associated with age, sex, pretreatment T stage, or surgeons' experience.
      CONCLUSIONS: Our data shows that robot-assisted ISR for low rectal cancer is
      feasible and safe with no compromising oncological outcomes. The surgeons'
      experience improves operating time in robotic surgery.

PMID- 24562550
TI  - Reduced forms of the Wigner distribution function for the numerical analysis of
      rotationally symmetric synchrotron radiation.
AB  - In an effort to provide a computationally convenient approach to the
      characterization of partially coherent synchrotron radiation in phase space, a
      thorough discussion of the minimum dimensionality of the Wigner distribution
      function for rotationally symmetric sources of arbitrary degrees of coherence is
      presented. It is found that perfectly coherent, perfectly incoherent and
      partially coherent sources may all be characterized by a three-dimensional
      reduced Wigner distribution function, and some special cases are discussed in
      which a two-dimensional reduced Wigner distribution function suffices. An
      application of the dimension-reducing formalism to the case of partially coherent
      radiation from a planar undulator and a circularly symmetric electron beam as can
      be found in linear accelerators is demonstrated. The photon distribution is
      convolved over a realistic electron bunch, and how the beta function, emittance
      and energy spread of the bunch affect the total degree of coherence of the
      radiation is inspected. Finally the cross spectral density is diagonalized and
      the eigenmodes of the partially coherent radiation are recovered. 

PMID- 24562547
TI  - DNA fragmentation and caspase-independent programmed cell death by modulated
      electrohyperthermia.
AB  - BACKGROUND AND PURPOSE: The electric field and the concomitant heat
      (electrohyperthermia) can synergistically induce cell death in tumor tissue, due
      to elevated glycolysis, ion concentration, and permittivity in malignant compared
      with nonmalignant tissues. Here we studied the mechanism and time course of tumor
      destruction caused by electrohyperthermia. MATERIAL AND METHODS: Bilateral
      implants of HT29 colorectal cancer in the femoral regions of Balb/c (nu/nu) mice
      were treated with a single 30-min shot of modulated, 13.56-MHz, radiofrequency
      generated electrohyperthermia (mEHT). Tumors at 0, 1, 4, 8, 14, 24, 48, and 72 h
      posttreatment were studied for morphology, DNA fragmentation, and cell death
      response-related protein expression using tissue microarrays,
      immunohistochemistry, Western immunoblots, and terminal deoxynucleotidyl
      transferase dUTP nick end labeling (TUNEL) assays. RESULTS: Modulated EHT
      treatment induced significant tumor destruction in HT29 xenografts with a peak of
      a sevenfold increase compared with the untreated controls. The significant
      treatment-related elevation of DNA fragmentation--detected with TUNEL assay--and
      apoptotic bodies between 24 and 72 h posttreatment was proof of a programmed cell
      death response. This was associated with significant mitochondrial accumulation
      of bax and mitochondrial-to-cytoplasmic release of cytochrome c proteins between
      8 and 14 h. Cleaved caspase-3 levels were low and mainly localized to
      inflammatory cells. The substantial cytoplasmic-to-nuclear translocation of
      apoptosis-inducing factor (AIF) and its 57-kDa activated fragment detected
      between 14 and 24 h after treatment indicated AIF as an effector for DNA
      fragmentation. CONCLUSION: Modulated EHT treatment can induce programmed cell
      death-related tumor destruction in HT29 colorectal adenocarcinoma xenografts,
      which dominantly follows a caspase-independent subroutine.

PMID- 24562551
TI  - Characterization, optimization and surface physics aspects of in situ plasma
      mirror cleaning.
AB  - Although the graphitic carbon contamination of synchrotron beamline optics has
      been an obvious problem for several decades, the basic mechanisms underlying the
      contamination process as well as the cleaning/remediation strategies are not
      understood and the corresponding cleaning procedures are still under development.
      In this study an analysis of remediation strategies all based on in situ low
      pressure RF plasma cleaning approaches is reported, including a quantitative
      determination of the optimum process parameters and their influence on the
      chemistry as well as the morphology of optical test surfaces. It appears that
      optimum results are obtained for a specific pressure range as well as for
      specific combinations of the plasma feedstock gases, the latter depending on the
      chemical aspects of the optical surfaces to be cleaned. 

PMID- 24562549
TI  - Clinical practice guideline on diagnosis and treatment of hyponatraemia.
AB  - Hyponatraemia, defined as a serum sodium concentration <135 mmol/L, is the most
      common disorder of body fluid and electrolyte balance encountered in clinical
      practice. Hyponatraemia is present in 15-20% of emergency admissions to hospital
      and occurs in up to 20% of critically ill patients. Symptomatology may vary from
      subtle to severe or even life threatening. Despite this, the management of
      patients remains problematic. Against this background, the European Society of
      Intensive Care Medicine, the European Society of Endocrinology and the European
      Renal Association-European Dialysis and Transplant Association, represented by
      European Renal Best Practice have developed a Clinical Practice Guideline on the
      diagnostic approach and treatment of hyponatraemia as a joint venture of three
      societies representing specialists with a natural interest in hyponatraemia.

PMID- 24562552
TI  - Performance of a silicon monochromator under high heat load.
AB  - The performance of a cryogenically cooled double-crystal silicon monochromator
      was studied under high-heat-load conditions with total absorbed powers and power
      densities ranging from 8 to 780 W and from 8 to 240 W mm(-2), respectively. When
      the temperature of the first crystal is maintained close to the temperature of
      zero thermal expansion of silicon, the monochromator shows nearly ideal
      performance with a thermal slope error of 0.6 urad. By tuning the size of the
      first slit, the regime of the ideal performance can be maintained over a wide
      range of heat loads, i.e. from power densities of 110 W mm(-2) (at total absorbed
      power of 510 W) to 240 W mm(-2) (at total absorbed power of 240 W). 

PMID- 24562553
TI  - Highly efficient beamline and spectrometer for inelastic soft X-ray scattering at
      high resolution.
AB  - The design, construction and commissioning of a beamline and spectrometer for
      inelastic soft X-ray scattering at high resolution in a highly efficient system
      are presented. Based on the energy-compensation principle of grating dispersion,
      the design of the monochromator-spectrometer system greatly enhances the
      efficiency of measurement of inelastic soft X-rays scattering. Comprising two
      bendable gratings, the set-up effectively diminishes the defocus and coma
      aberrations. At commissioning, this system showed results of spin-flip, d-d and
      charge-transfer excitations of NiO. These results are consistent with published
      results but exhibit improved spectral resolution and increased efficiency of
      measurement. The best energy resolution of the set-up in terms of full width at
      half-maximum is 108 meV at an incident photon energy tuned about the Ni L3-edge. 

PMID- 24562554
TI  - In situ micro-focused X-ray beam characterization with a lensless camera using a
      hybrid pixel detector.
AB  - Results of studies on micro-focused X-ray beam diagnostics using an X-ray beam
      imaging (XBI) instrument based on the idea of recording radiation scattered from
      a thin foil of a low-Z material with a lensless camera are reported. The XBI
      instrument captures magnified images of the scattering region within the foil as
      illuminated by the incident beam. These images contain information about beam
      size, beam position and beam intensity that is extracted during dedicated signal
      processing steps. In this work the use of the device with beams for which the
      beam size is significantly smaller than that of a single detector pixel is
      explored. The performance of the XBI device equipped with a state-of-the-art
      hybrid pixel X-ray imaging sensor is analysed. Compared with traditional methods
      such as slit edge or wire scanners, the XBI micro-focused beam characterization
      is significantly faster and does not interfere with on-going experiments. The
      challenges associated with measuring micrometre-sized beams are described and
      ways of optimizing the resolution of beam position and size measurements of the
      XBI instrument are discussed. 

PMID- 24562555
TI  - D3, the new diffractometer for the macromolecular crystallography beamlines of
      the Swiss Light Source.
AB  - A new diffractometer for microcrystallography has been developed for the three
      macromolecular crystallography beamlines of the Swiss Light Source. Building upon
      and critically extending previous developments realised for the high-resolution
      endstations of the two undulator beamlines X06SA and X10SA, as well as the super
      bend dipole beamline X06DA, the new diffractometer was designed to the following
      core design goals. (i) Redesign of the goniometer to a sub-micrometer peak-to
      peak cylinder of confusion for the horizontal single axis. Crystal sizes down to
      at least 5 um and advanced sample-rastering and scanning modes are supported. In
      addition, it can accommodate the new multi-axis goniometer PRIGo (Parallel
      Robotics Inspired Goniometer). (ii) A rapid-change beam-shaping element system
      with aperture sizes down to a minimum of 10 um for microcrystallography
      measurements. (iii) Integration of the on-axis microspectrophotometer MS3 for
      microscopic sample imaging with 1 um image resolution. Its multi-mode optical
      spectroscopy module is always online and supports in situ UV/Vis absorption,
      fluorescence and Raman spectroscopy. (iv) High stability of the sample
      environment by a mineral cast support construction and by close containment of
      the cryo-stream. Further features are the support for in situ crystallization
      plate screening and a minimal achievable detector distance of 120 mm for the
      Pilatus 6M, 2M and the macromolecular crystallography group's planned future area
      detector Eiger 16M. 

PMID- 24562557
TI  - Expected thermal deformation and wavefront preservation of a cryogenic Si
      monochromator for Cornell ERL beamlines.
AB  - Cornell energy-recovery linac (ERL) beamlines will have higher power density and
      higher fractional coherence than those available at third-generation sources;
      therefore the capability of a monochromator for ERL beamlines has to be studied.
      A cryogenic Si monochromator is considered in this paper because the perfect
      atomic structure of Si crystal is needed to deliver highly coherent radiation.
      Since neither the total heat load nor the power density alone can determine the
      severity of crystal deformation, a metric called modified linear power density is
      used to gauge the thermal deformation. For all ERL undulator beamlines, crystal
      thermal deformation profiles are simulated using the finite-element analysis tool
      ANSYS, and wavefront propagations are simulated using Synchrotron Radiation
      Workshop. It is concluded that cryogenic Si monochromators will be suitable for
      ERL beamlines in general. 

PMID- 24562556
TI  - New soft X-ray beamline BL07LSU at SPring-8.
AB  - A new soft X-ray beamline, BL07LSU, has been constructed at SPring-8 to perform
      advanced soft X-ray spectroscopy for materials science. The beamline is designed
      to achieve high energy resolution (E/DeltaE> 10000) and high photon flux [>10(12)
      photons s(-1) (0.01% bandwidth)(-1)] in the photon energy range 250-2000 eV with
      controllable polarization. To realise this state-of-the-art performance, a novel
      segmented cross undulator was developed and adopted as a light source. The
      details of the undulator light source and beamline monochromator design are
      described. The achieved performance of the beamline, such as the photon flux,
      energy resolution and the state of polarization, is reported. 

PMID- 24562558
TI  - A compact synchrotron-based transmission X-ray microscope.
AB  - A compact transmission X-ray microscope has been designed and implemented based
      on a cylindrical symmetry around the optical axis that sharply limits the
      instabilities due to thermal mechanical drift. Identical compact multi-axis
      closed-loop actuation modules drive different optical components. The design is
      modular and simplifies the change of individual parts, e.g. the use of different
      magnification and focusing devices. This compact instrument can be easily
      transported between laboratory and synchrotron facilities and quickly put into
      operation. An automated alignment mechanism simplifies the assembly of different
      modules after transportation. After describing the design details, the results of
      the first tests are presented. 

PMID- 24562559
TI  - Ultrafast switching of hard X-rays.
AB  - A new concept for shortening hard X-ray pulses emitted from a third-generation
      synchrotron source down to few picoseconds is presented. The device, called the
      PicoSwitch, exploits the dynamics of coherent acoustic phonons in a photo-excited
      thin film. A characterization of the structure demonstrates switching times of <=
      5 ps and a peak reflectivity of ~10(-3). The device is tested in a real
      synchrotron-based pump-probe experiment and reveals features of coherent phonon
      propagation in a second thin film sample, thus demonstrating the potential to
      significantly improve the temporal resolution at existing synchrotron facilities.

PMID- 24562560
TI  - The power of in situ pulsed laser deposition synchrotron characterization for the
      detection of domain formation during growth of Ba0.5Sr0.5TiO3 on MgO.
AB  - A highly sophisticated pulsed laser deposition (PLD) chamber has recently been
      installed at the NANO beamline at the synchrotron facility ANKA (Karlsruhe,
      Germany), which allows for comprehensive studies on the PLD growth process of
      dielectric, ferroelectric and ferromagnetic thin films in epitaxial oxide
      heterostructures or even multilayer systems by combining in situ reflective high
      energy diffraction with the in situ synchrotron high-resolution X-ray diffraction
      and surface diffraction methods. The modularity of the in situ PLD chamber offers
      the opportunity to explore the microstructure of the grown thin films as a
      function of the substrate temperature, gas pressure, laser fluence and target
      substrate separation distance. Ba0.5Sr0.5TiO3 grown on MgO represents the first
      system that is grown in this in situ PLD chamber and studied by in situ X-ray
      reflectivity, in situ two-dimensional reciprocal space mapping of symmetric X-ray
      diffraction and acquisition of time-resolved diffraction profiles during the
      ablation process. In situ PLD synchrotron investigation has revealed the
      occurrence of structural distortion as well as domain formation and misfit
      dislocation which all depend strongly on the film thickness. The microstructure
      transformation has been accurately detected with a time resolution of 1 s. The
      acquisition of two-dimensional reciprocal space maps during the PLD growth has
      the advantage of simultaneously monitoring the changes of the crystalline
      structure as well as the formation of defects. The stability of the morphology
      during the PLD growth is demonstrated to be remarkably affected by the film
      thickness. A critical thickness for the domain formation in Ba0.5Sr0.5TiO3 grown
      on MgO could be determined from the acquisition of time-resolved diffraction
      profiles during the PLD growth. A splitting of the diffraction peak into two
      distinguishable peaks has revealed a morphology change due to modification of the
      internal strain during growth. 

PMID- 24562561
TI  - Studying the surface reaction between NiO and Al2O3 via total reflection EXAFS
      (ReflEXAFS).
AB  - The reaction between NiO and (0001)- and (1102)-oriented Al2O3 single crystals
      has been investigated on model experimental systems by using the ReflEXAFS
      technique. Depth-sensitive information is obtained by collecting data above and
      below the critical angle for total reflection. A systematic protocol for data
      analysis, based on the recently developed CARD code, was implemented, and a
      detailed description of the reactive systems was obtained. In particular, for
      (1102)-oriented Al2O3, the reaction with NiO is almost complete after heating for
      6 h at 1273 K, and an almost uniform layer of spinel is found below a mixed (NiO
      + spinel) layer at the very upmost part of the sample. In the case of the (0001)
      oriented Al2O3, for the same temperature and heating time, the reaction shows a
      lower advancement degree and a residual fraction of at least 30% NiO is detected
      in the ReflEXAFS spectra.

PMID- 24562562
TI  - Position and flux stabilization of X-ray beams produced by double-crystal
      monochromators for EXAFS scans at the titanium K-edge.
AB  - The simultaneous and active feedback stabilization of X-ray beam position and
      monochromatic beam flux during EXAFS scans at the titanium K-edge as produced by
      a double-crystal monochromator beamline is reported. The feedback is generated
      using two independent feedback loops using separate beam flux and position
      measurements. The flux is stabilized using a fast extremum-searching algorithm
      that is insensitive to changes in the synchrotron ring current and energy
      dependent monochromator output. Corrections of beam height are made using an
      innovative transmissive beam position monitor instrument. The efficacy of the
      feedback stabilization method is demonstrated by comparing the measurements of
      EXAFS spectra on inhomogeneous diluted Ti-containing samples with and without
      feedback applied. 

PMID- 24562563
TI  - Local structure of amorphous tellurium studied by EXAFS.
AB  - The local structure of an amorphous tellurium (a-Te) film was investigated by
      extended X-ray absorption fine-structure analysis. The covalent bond length
      shortens and the Debye-Waller factor of the intra-chain decreases in a-Te
      compared with trigonal Te (t-Te). The value of the intra-chain coordination
      number is close to two, which is the value for t-Te, and the inter-chain
      interaction weakens. These results suggest that the primary chain structure
      remains intact, but the secondary structure is disrupted. The decrease in the
      inter-chain interaction strengthens the intra-chain interaction. 

PMID- 24562564
TI  - Measurement of the X-ray mass attenuation coefficients of silver in the 5-20 keV
      range.
AB  - The X-ray mass attenuation coefficients of silver were measured in the energy
      range 5-20 keV with an accuracy of 0.01-0.2% on a relative scale down to 5.3 keV,
      and of 0.09-1.22% on an absolute scale to 5.0 keV. This analysis confirms that
      with careful choice of foil thickness and careful correction for systematics,
      especially including harmonic contents at lower energies, the X-ray attenuation
      of high-Z elements can be measured with high accuracy even at low X-ray energies
      (<6 keV). This is the first high-accuracy measurement of X-ray mass attenuation
      coefficients of silver in the low energy range, indicating the possibility of
      obtaining high-accuracy X-ray absorption fine structure down to the L1 edge (3.8
      keV) of silver. Comparison of results reported here with an earlier data set
      optimized for higher energies confirms accuracy to within one standard error of
      each data set collected and analysed using the principles of the X-ray extended
      range technique (XERT). Comparison with theory shows a slow divergence towards
      lower energies in this region away from absorption edges. The methodology
      developed can be used for the XAFS analysis of compounds and solutions to
      investigate structural features, bonding and coordination chemistry. 

PMID- 24562565
TI  - Simultaneous measurement of bubble size, velocity and void fraction in two-phase
      bubbly flows with time-resolved X-ray imaging.
AB  - Key parameters of two-phase flows, such as void fraction and microscale bubble
      size, shape and velocity, were simultaneously measured using time-resolved X-ray
      imaging. X-ray phase-contrast imaging was employed to obtain those parameters on
      microbubbles. The void fraction was estimated from X-ray absorption. The radii of
      the measured microbubbles were mostly smaller than 20 um, and the maximum
      velocity was 39.442 mm s(-1), much higher than that in previous studies. The
      spatial variations of the void fraction were consecutively obtained with a small
      time interval. This technique would be useful in the experimental analysis of
      bubbly flows in which microbubbles move at high speed. 

PMID- 24562566
TI  - Feasibility study of propagation-based phase-contrast X-ray lung imaging on the
      Imaging and Medical beamline at the Australian Synchrotron.
AB  - Propagation-based phase-contrast X-ray imaging (PB-PCXI) using synchrotron
      radiation has achieved high-resolution imaging of the lungs of small animals both
      in real time and in vivo. Current studies are applying such imaging techniques to
      lung disease models to aid in diagnosis and treatment development. At the
      Australian Synchrotron, the Imaging and Medical beamline (IMBL) is well equipped
      for PB-PCXI, combining high flux and coherence with a beam size sufficient to
      image large animals, such as sheep, due to a wiggler source and source-to-sample
      distances of over 137 m. This study aimed to measure the capabilities of PB-PCXI
      on IMBL for imaging small animal lungs to study lung disease. The feasibility of
      combining this technique with computed tomography for three-dimensional imaging
      and X-ray velocimetry for studies of airflow and non-invasive lung function
      testing was also investigated. Detailed analysis of the role of the effective
      source size and sample-to-detector distance on lung image contrast was undertaken
      as well as phase retrieval for sample volume analysis. Results showed that PB
      PCXI of lung phantoms and mouse lungs produced high-contrast images, with
      successful computed tomography and velocimetry also being carried out, suggesting
      that live animal lung imaging will also be feasible at the IMBL. 

PMID- 24562567
TI  - Point spread function measurement of an X-ray beam focused by a multilayer zone
      plate with narrow annular aperture.
AB  - The experimental procedure for obtaining the point spread function (PSF) of a
      focusing beam generated using an X-ray multilayer zone plate (MZP) with a narrow
      annular aperture has been developed. It was possible to reconstruct the PSF by
      applying the tomographic process to the measured dataset consisting of line
      spread functions (LSFs) in every radial direction on the focal plane. The LSFs
      were measured by a knife-edge scanning method of detecting scattered intensity.
      In the experimental work, quasi-monochromatic undulator radiation with a first
      harmonic energy of 20 keV was directly focused without a monochromator by the
      MZP, and the PSF was measured using this procedure. As a result, a near
      diffraction-limited focused beam size of 46 nm full width at half-maximum was
      obtained. 

PMID- 24562568
TI  - Object image correction using an X-ray dynamical diffraction Fraunhofer hologram.
AB  - Taking into account background correction and using Fourier analysis, a numerical
      method of an object image correction using an X-ray dynamical diffraction
      Fraunhofer hologram is presented. An example of the image correction of a
      cylindrical beryllium wire is considered. A background correction of second-order
      iteration leads to an almost precise reconstruction of the real part of the
      amplitude transmission coefficient and improves the imaginary part compared with
      that without a background correction. Using Fourier analysis of the reconstructed
      transmission coefficient, non-physical oscillations can be avoided. This method
      can be applied for the determination of the complex amplitude transmission
      coefficient of amplitude as well as phase objects, and can be used in X-ray
      microscopy. 

PMID- 24562569
TI  - Design and performance of a new VIS-VUV photoluminescence beamline at UVSOR-III.
AB  - A new bending-magnet beamline with a 2.5 m normal-incidence monochromator has
      been constructed to serve with a light source in the visible-vacuum-ultraviolet
      region for photoluminescence, transmission and reflection spectroscopies of
      solids at the UVSOR-III 750 MeV synchrotron radiation light source. The aim is to
      pave the way to establishing a beamline with high photon flux, high brilliance,
      high energy-resolution, high linear-polarization and low higher-order light. To
      obtain high photon flux and brilliance, the acceptance angle of the bending
      magnet radiation was designed to be 40 mrad (H) * 14 mrad (V) and the post-mirror
      system employed Kirkpatrick-Baez optics. The incidence angle of the incoming
      light to the optical elements, except to the gratings, was set to a grazing angle
      in order to keep a degree of linear polarization. For achieving high energy
      resolution, an off-plane Eagle-type monochromator was adopted. Higher-order
      unwanted light in the energy range below ~11 eV was suppressed to be less than
      0.1%. 

PMID- 24562570
TI  - Image stack alignment in full-field X-ray absorption spectroscopy using
      SIFT_PyOCL.
AB  - Full-field X-ray absorption spectroscopy experiments allow the acquisition of
      millions of spectra within minutes. However, the construction of the
      hyperspectral image requires an image alignment procedure with sub-pixel
      precision. While the image correlation algorithm has originally been used for
      image re-alignment using translations, the Scale Invariant Feature Transform
      (SIFT) algorithm (which is by design robust versus rotation, illumination change,
      translation and scaling) presents an additional advantage: the alignment can be
      limited to a region of interest of any arbitrary shape. In this context, a Python
      module, named SIFT_PyOCL, has been developed. It implements a parallel version of
      the SIFT algorithm in OpenCL, providing high-speed image registration and
      alignment both on processors and graphics cards. The performance of the algorithm
      allows online processing of large datasets. 

PMID- 24562571
TI  - A high-pressure and controlled-flow gas system for catalysis research.
AB  - A high-pressure gas rig for in situ catalytic reactions at X-ray absorption
      spectroscopy beamline (BM26A) has been developed. The rig enables catalysts to be
      studied in a variety of cells under well controlled and industrially relevant
      operation conditions. A large variety of gas mixtures can be generated and
      pressures of up to 50 bar with dry gas and 20 bar with wet gas (steam) can be
      obtained. Analyses of reaction products can be performed using an on-line mass
      spectrometer. 

PMID- 24562573
TI  - Fluorogen-activating scFv biosensors target surface markers on live cells via
      streptavidin or single-chain avidin.
AB  - Fluorescence biosensors are indispensable tools for understanding protein
      behavior and function in cells. Recent advancements utilize fluorogen-activating
      proteins (FAPs) that form complexes with small organic molecules (fluorogens) and
      result in their fluorescence activation. The technology has found multiple uses
      in protein discovery applications; however, the current method of detection
      requires the expression of FAPs as gene fusion tags in cells-a process that is
      time- and labor-intensive. In this report, we present an alternate method that
      utilizes FAPs as affinity reagents. Accordingly, we isolated soluble reagents
      based on FAP fusions with streptavidin (Strep) or avidin proteins, both highly
      selective for biotin. When tested in vitro, the reagents displayed bi-functional
      activity, fluorogen activation, and biotin affinity. For live-cell protein
      discovery, surface targets were biotinylated via biotin-tagged immunoglobulins or
      a genetically encoded biotin acceptor peptide. As a result, when the cells were
      labeled with FAP-Strep or FAP-avidin reagent, the in vivo fluorescence
      measurements indicated high target specificity, minimal background, and bright
      signal detection. In summary, we present a novel FAP reagent platform that offers
      a rapid and efficient approach for cell surface protein detection.

PMID- 24562575
TI  - GPX2 overexpression is involved in cell proliferation and prognosis of castration
      resistant prostate cancer.
AB  - There is a need for exploration of new therapeutic strategies that target
      distinct molecular mechanisms of castration-resistant prostate cancer (CRPC)
      because its emergence following androgen deprivation therapy is a major clinical
      problem. In this report, we investigated the role of glutathione peroxidase 2
      (GPX2) in CRPC. GPX2 expression was analyzed in rat and human CRPC cells. Next,
      we determined the proliferation rate and level of reactive oxygen species (ROS)
      in GPX2-small interfering RNA (siRNA)-transfected CRPC cells. For in vivo
      analysis, siRNA-transfected cells were subcutaneously implanted into normal and
      castrated nude mice. Further, immunohistochemical and prognostic analyses of GPX2
      were performed using human specimens. Silencing of GPX2 caused significant growth
      inhibition and increased intracellular ROS in both rat (PCai1) and human (PC3)
      CRPC cells. Flow cytometry and western blot analyses revealed that the decrease
      in proliferation rate of the GPX2-silenced cells was due to cyclin B1-dependent
      G2/M arrest. Furthermore, knockdown of Gpx2 inhibited tumor growth of PCai1 cells
      in castrated mice. Immunohistochemical analyses indicated that expression of GPX2
      was significantly higher in residual cancer foci after neoadjuvant hormonal
      therapy than in hormone naive cancer foci. Moreover, patients with high GPX2
      expression in biopsy specimen had significantly lower prostate-specific antigen
      recurrence-free survival and overall survival than those with no GPX2 expression.
      These findings suggest that GPX2 is a prognostic marker in CRPC and affects
      proliferation of prostate cancer under androgen depletion partially through
      protection against ROS signaling. 

PMID- 24562574
TI  - Combination of AKT inhibition with autophagy blockade effectively reduces ascites
      derived ovarian cancer cell viability.
AB  - Recent genomics analysis of the high-grade serous subtype of epithelial ovarian
      cancer (EOC) show aberrations in the phosphatidylinositol 3-kinase (PI3K)/AKT
      pathway that result in upregulated signaling activity. Thus, the PI3K/AKT pathway
      represents a potential therapeutic target for aggressive high-grade EOC. We
      previously demonstrated that treatment of malignant ascites-derived primary human
      EOC cells and ovarian cancer cell lines with the allosteric AKT inhibitor Akti
      1/2 induces a dormancy-like cytostatic response but does not reduce cell
      viability. In this report, we show that allosteric AKT inhibition in these cells
      induces cytoprotective autophagy. Inhibition of autophagy using chloroquine (CQ)
      alone or in combination with Akti-1/2 leads to a significant decrease in viable
      cell number. In fact, Akti-1/2 sensitizes EOC cells to CQ-induced cell death by
      exhibiting markedly reduced EC50 values in combination-treated cells compared
      with CQ alone. In addition, we evaluated the effects of the novel specific and
      potent autophagy inhibitor-1 (Spautin-1) and demonstrate that Spautin-1 inhibits
      autophagy in a Beclin-1-independent manner in primary EOC cells and cell lines.
      Multicellular EOC spheroids are highly sensitive to Akti-1/2 and CQ/Spautin-1
      cotreatments, but resistant to each agent alone. Indeed, combination index
      analysis revealed strong synergy between Akti-1/2 and Spautin-1 when both agents
      were used to affect cell viability; Akti-1/2 and CQ cotreatment also displayed
      synergy in most samples. Taken together, we propose that combination AKT
      inhibition and autophagy blockade would prove efficacious to reduce residual EOC
      cells for supplying ovarian cancer recurrence. 

PMID- 24562588
TI  - Simvastatin suppresses head and neck squamous cell carcinoma ex vivo and enhances
      the cytostatic effects of chemotherapeutics.
AB  - PURPOSE: Simvastatin (Sim) is approved as lipid-controlling drug in patients with
      cardiovascular risk to reduce hypercholesterolemia. Recent publications indicate
      possible inhibitory effects of Sim on tumor cell lines, and epidemiological data
      suggest activity in cancer patients. Still, its therapeutic efficacy,
      particularly in head and neck squamous cell carcinoma (HNSCC), remains to be
      elucidated. This study analyzes the effects of Sim on HNSCC cell lines (KB, HN5,
      FaDu) and on a larger set of primary HNSCC cells by employing a short-time ex
      vivo colony formation test (FLAVINO assay). Possible additive or synergistic
      effects of Sim combinations with established chemotherapeutics are determined as
      well. METHODS: Biopsies of 49 HNSCC were tested in the FLAVINO assay with Sim
      alone or in combination with cisplatin (Cis) or docetaxel (DTX). Cell lines were
      studied for reference. Epithelial HNSCC cells were stained by Cy2-labeled anti
      cytokeratin antibodies facilitating the detection of colony formation (CF) by
      immunofluorescence. Drug combinations were analyzed regarding their interaction.
      RESULTS: Sim alone acted suppressive on tested cell lines and increased the
      cytostatic efficacy of Cis and DTX. 18/49 HNSCC qualified for FLAVINO-based dose
      response analyses, and Sim significantly suppressed CF in 18/18 primary HNSCC.
      Moreover, Sim increased cytotoxic effects of Cis and DTX, primarily in an
      additive mode of action. CONCLUSIONS: The ex vivo tumor cell inhibition of Sim
      and its additive effects upon combination with established cytostatics provide
      the basis for epidemiological and clinical studies on statins, potentially
      directed toward co-medication in future treatment regimens.

PMID- 24562589
TI  - A phase II study of capecitabine plus docetaxel in gemcitabine-pretreated
      metastatic pancreatic cancer patients: CapTere.
AB  - PURPOSE: Docetaxel and capecitabine combination is synergistic in preclinical
      models. We investigated the efficacy and toxicity of this combination as second
      line chemotherapy in patients with metastatic pancreatic adenocarcinoma (mPC),
      pretreated with gemcitabine-based chemotherapy. METHODS: Eligible patients were
      treated with capecitabine 800 mg/m(2) orally PO bid on days 1-14 in combination
      with intravenous docetaxel 30 mg/m(2) on days 1 and 8 of each 21-day cycle. The
      primary end point was overall response rate. Using a three-stage sequential
      design, two interim analyses for early stopping due to lack of efficacy were
      planned and conducted after 13 and 26 patients were accrued. Secondary end points
      included time to treatment failure, progression-free survival (PFS), overall
      survival (OS) and 50 % drop in CA19-9 levels. RESULTS: Forty-three patients were
      evaluable for toxicity and 42 evaluable for response, at a median age of 64
      years. The majority of patients (74 %) had ECOG PS 0-1. Six patients (14 %)
      achieved a partial tumor response, and stable disease for >=2 cycles was observed
      in 59 % of patients (n = 25). Thirty-five percent (n = 11/31) of patients had a
      >=50 % decrease in CA19-9 levels. The median PFS was 3.7 months (95 % CI 2.1-4.3
      months), and the median OS was 5.3 months (95 % CI 4.3-8.6 months). Treatment was
      generally well tolerated. Grade 3 toxicity and grade 4 toxicity were seen in 45
      and 5 % of patients, respectively. One patient had a potential treatment-related
      mortality. CONCLUSIONS: The combination of capecitabine and docetaxel is active
      and well tolerated in mPC patients pretreated with gemcitabine-based therapy.

PMID- 24562590
TI  - Resting-state functional magnetic resonance imaging in hepatic encephalopathy:
      current status and perspectives.
AB  - Hepatic encephalopathy (HE) is a neuropsychiatric syndrome which develops in
      patients with severe liver diseases and/or portal-systemic shunting. Minimal HE,
      the earliest manifestation of HE, has drawn increasing attention in the last
      decade. Minimal HE is associated with a series of brain functional changes, such
      as attention, working memory, and so on. Blood oxygen level dependent (BOLD)
      functional MRI (fMRI), especially resting-state fMRI has been used to explore the
      brain functional changes of HE, yielding important insights for understanding
      pathophysiological mechanisms and functional reorganization of HE. This paper
      briefly reviews the principles of BOLD fMRI, potential applications of resting
      state fMRI with advanced post-processing algorithms such as regional homogeneity,
      amplitude of low frequency fluctuation, functional connectivity and future
      research perspective in this field. 

PMID- 24562592
TI  - The effect of single nucleotide polymorphisms in the tumor necrosis factor-alpha
      gene on reproductive performance and immune function in dairy cattle.
AB  - The present study aimed to assess the effect of polymorphisms in the tumor
      necrosis factor alpha (TNF-alpha) promoter (A/A, A/G and G/G) and exons (T/T, T/C
      and C/C) on immune function and reproductive performance in dairy cows. The
      occurrence of the first postpartum ovulation within 3 weeks in the cows with the
      TNF-alpha promoter A/G and G/G genotypes was higher than in the A/A group. Among
      the different TNF-alpha exon genotypes, the occurrence of early first postpartum
      ovulation was higher in the T/C and C/C genotype groups than in the T/T group.
      Single nucleotide polymorphisms (SNPs) in the TNF-alpha gene did not affect the
      rate of artificial insemination (AI) or duration from parturition to next
      conception (days open). The apoptosis rate of polymorphonuclear leukocytes (PMNs)
      did not differ among the TNF-alpha promoter genotypes, but the PMN transmigration
      rate was significantly higher for the A/A and A/G genotypes than for the G/G
      genotype. Interleukin 8 (IL-8) mRNA expression in PMNs and peripheral blood
      mononuclear cells (PBMCs) before culture was significantly higher for the A/A
      genotype compared with the G/G genotype. There were no significant differences
      between the genotypes in the mRNA expression of TNF-alpha, IL-6, IL-1beta, and
      toll-like receptor 4 (TLR4) in PMNs and PBMCs before and 4 h after culture. IL-8
      and IL-1beta production by PBMCs cultured for 4 h was significantly higher for
      the animals with the A/A genotype than for those with the G/G genotype. On the
      other hand, no significant difference was observed in IL-8 and IL-1beta
      production by PMNs among different TNF-alpha genotypes. Taken together, these
      results suggest that SNP in the TNF-alpha gene affects immune function and
      reproductive performance in dairy cows. 

PMID- 24562593
TI  - Keratometry with five different techniques: a study of device repeatability and
      inter-device agreement.
AB  - The purpose of this study was to determine and compare the repeatability of
      keratometry measurements with the Javal manual keratometer, Topcon automated
      kerato-refractometer, IOLMaster, EyeSys Corneal Analysis System, and Pentacam
      Scheimpflug Topography System, and determine the agreement of measurements of the
      latter four devices with the Javal keratometer as the gold standard. In this
      cross-sectional study, 21 people with no history of ocular disease or surgery
      were examined twice with each device. Minimum, maximum, and average keratometry
      readings were recorded in diopters (D) for each eye and used in the analyses. For
      statistical analysis, we determined correlation coefficients and used the Bland
      Altman method and calculated the 95 % limits of agreement (LoA). All
      repeatability coefficients were satisfactorily high. Best repeatability for
      minimum keratometry and maximum keratometry readings was seen with IOLMaster (95
      % LoA -0.23 to 0.19 D and -0.31 to 0.32 D, respectively). Agreement with Javal
      manual keratometry was best with Topcon and IOLMaster for minimum keratometry
      readings (95 % LoA -0.67 to 0.28 D and -0.57 to 0.38 D, respectively), and with
      Topcon for maximum keratometry readings (95 % LoA -0.85 to 0.63 D). In our series
      of normal eyes, keratometry readings with Topcon, IOLMaster, and Pentacam showed
      very good agreement with Javal measurements, and inter-device agreements were
      better than the repeatability of the manual gold standard. However, differences
      between Javal and EyeSys may not be clinically acceptable, and these two devices
      should not be used interchangeably. Further studies are needed to investigate
      these issues in non-virgin eyes.

PMID- 24562594
TI  - Do air pressure and wind speed influence the outcome of myopic laser refractive
      surgery? Results from the Hamburg Weather Study.
AB  - Laser in situ keratomileusis (LASIK) is one of the dominant procedures for the
      surgical correction of refractive errors. Meteorotropic reaction has been
      described regarding the field of ophthalmology. This study was thus initiated to
      assess the impact of air pressure and wind speed on the refractive and visual
      outcome of LASIK in myopic eyes. Our study comprised 1,052 eyes of 1,052
      consecutive myopic patients (419 males, 633 females; mean age at surgery 35.0 +/-
      9.0 years) with mean preoperative refractive spherical equivalent (SE) of -3.88
      +/- 1.85 diopters (D). Two subgroups were defined, which had undergone surgery
      either during meteorological winter or summer. Manifest refraction, uncorrected
      and corrected visual acuity were assessed pre- and post-operatively. We applied
      robust regression analysis with efficiency index (EI), safety index, and
      postoperative SE (D) as dependent variables. At the 1-month (33.0 +/- 5.0 days)
      follow-up, the mean postoperative SE was -0.18 +/- 0.44 D. Bivariate comparisons
      showed that statistically significant better EI was related to days with low to
      moderate air-pressure. This was confirmed by robust regression analysis. Moderate
      to high wind speed was related to more appropriate postoperative SE. No change by
      more than one line on logMar scale was obtained. Although being statistically
      significant, there is no clinically relevant difference in outcome of LASIK,
      which demonstrates its highly standardized quality. Prospective, longitudinal
      studies are warranted to address meteorotropic reactions through evaluating
      individual risk profiles.

PMID- 24562595
TI  - A dual-radioisotope hybrid whole-body micro-positron emission tomography/computed
      tomography system reveals functional heterogeneity and early local and systemic
      changes following targeted radiation to the murine caudal skeleton.
AB  - The purpose of this study was to develop a longitudinal non-invasive functional
      imaging method using a dual-radioisotope hybrid micro-positron emission
      tomography/computed tomography (PET/CT) scanner in order to assess both the
      skeletal metabolic heterogeneity and the effect of localized radiation that
      models therapeutic cancer treatment on marrow and bone metabolism. Skeletally
      mature BALB/c female mice were given clinically relevant local radiation (16 Gy)
      to the hind limbs on day 0. Micro-PET/CT acquisition was performed serially for
      the same mice on days -5 and +2 with FDG and days -4 and +3 with NaF. Serum
      levels of pro-inflammatory cytokines were measured. Significant differences (p <
      0.0001) in marrow metabolism (measured by FDG) and bone metabolism (measured by
      NaF) were observed among bones before radiation, which demonstrates functional
      heterogeneity in the marrow and mineralized bone throughout the skeleton.
      Radiation significantly (p < 0.0001) decreased FDG uptake but increased NaF
      uptake (p = 0.0314) in both irradiated and non-irradiated bones at early time
      points. An increase in IL-6 was observed with a significant abscopal (distant)
      effect on marrow and bone metabolic function. Radiation significantly decreased
      circulating IGF-1 (p < 0.01). Non-invasive longitudinal imaging with dual
      radioisotope micro-PET/CT is feasible to investigate simultaneous changes in
      marrow and bone metabolic function at local and distant skeletal sites in
      response to focused radiation injury. Distinct local and remote changes may be
      affected by several cytokines activated early after local radiation exposure.
      This approach has the potential for longer-term studies to clarify the effects of
      radiation on marrow and bone.

PMID- 24562596
TI  - Venous thromboembolism in colorectal surgery: skip SCIP or comply?
AB  - BACKGROUND: The Surgical Care Improvement Project (SCIP) includes recommendations
      for mechanical and pharmacologic venous thromboembolism (VTE) prophylaxis after
      colorectal surgery. Compliance with these recommendations is publicly reported
      and included in current pay for performance plans. Presently, there is limited
      evidence to support compliance with these recommendations. AIM: To determine the
      incidence of venous thromboembolic events in colorectal surgery patients who did
      or did not receive the recommended pharmacologic prophylaxis. METHODS: We
      performed a retrospective analysis of prospectively accrued data from a single
      center, tertiary care, colorectal surgery department. The main outcome measure
      was the occurrence of venous thromboembolic events and the need for blood
      transfusion after surgery. RESULTS: Of 674 patients, 613(91%) received the
      recommended pharmacologic VTE prophylaxis and 61 (9%) did not. Diagnosis, patient
      variables, and type of surgery performed were similar in each group while
      operative time was increased in the compliant group (251 vs. 194 min, p < 0.05).
      In the compliant and noncompliant groups, the incidence of extremity deep venous
      thrombosis was 2.8 and 8.2% (p = 0.04), the incidence of pulmonary embolus 1.1
      and 3.3% (p = 0.19), the incidence of portomesenteric venous thrombosis 2.6 and
      4.9% (p = 0.38), and the incidence of any VTE 5.4 and 13.1% (p = 0.02),
      respectively. The use of perioperative red blood cell transfusions in the two
      groups was 9.1 and 14.8%, p = 0.17. In the subgroup analysis of open cases, there
      were no statistical differences in the occurrence of any type or combination of
      VTE. CONCLUSIONS: Compliance with SCIP recommendations for pharmacologic VTE
      prophylaxis decreased the incidence of VTE after colorectal surgery with no
      increase in the use of perioperative transfusion. Colorectal surgeons who elect
      to skip these recommendations may jeopardize both the reputational score and
      financial reimbursement of their hospital and may put their patients at
      unnecessary risk for a preventable postoperative complication.

PMID- 24562597
TI  - [Prehospital analgesia performed by paramedics: quality in processes and effects
      under medical supervision].
AB  - BACKGROUND: In the context of the new education program for German paramedics, a
      discussion has been fueled regarding the emergency care competencies of
      paramedics. In 1999 a system for training and qualification of paramedics was
      established in the emergency medical service (EMS) area of Reutlingen (Germany),
      including an algorithm for analgesia using ketamine and midazolam. Under defined
      circumstances analgesia may be administered to patients in the absence of a
      physician. AIM: The objectives of the study were to evaluate the effectiveness of
      pain reduction measured by a recognized assessment scale and the safety of
      analgesia with ketamine and midazolam administered by paramedics. This study
      specifically focused on the medical results and associated processes and not on
      the legal aspects. MATERIALS AND METHODS: In a retrospective analysis analgesia
      performed by paramedics who had undergone standardized training with annual
      controls and under medical supervision was investigated with regard to
      administration processes and efficacy. Analysis endpoints included vital signs at
      baseline and on transfer to the emergency department, pain score as defined by a
      numeric rating scale (NRS 0-10), the amount of ketamine administered and the
      occurrence of side effects (e.g. respiratory and circulatory disorders, nausea,
      qualitative and quantitative disturbance of consciousness). RESULTS: A total of
      528 instances of analgesia performed by paramedics were registered. The average
      patient age was 48 +/- 23 years (range 5-95 years). Trauma to the extremities was
      the most common indication for the administration of analgesia with 48 % and 38 %
      attributable to the upper and lower extremities, respectively. Serious
      complications were not observed. Administration of analgesia resulted in a highly
      significant reduction in pain scores (NRS p<0.0001). Mean initial pain score was
      8 with an interquartile range (IQR) of 7-8 and a 95% confidence interval (95% CI)
      of 7.5-7.9 which was decreased to 3 (IQR 2-3, 95% CI 2.2-2.7) on transfer to the
      emergency department. The number of patients with a pain score of NRS <=4 in the
      emergency department was 96 % (n=506). All other vital signs were essentially
      unchanged and the rate of side effects was low (2.8 %). Potentially life
      threatening complications were not reported. The mean midazolam dosage
      administered was 1 +/- 0.4 mg and the mean dosage of ketamine was 27 +/- 12 mg.
      The investigation was limited by restricted documentation and patients who were
      not treated with analgesics were not included in the study. CONCLUSION: After
      appropriate training and regular control analgesia administered by paramedics in
      the present system was safely and effectively applied.

PMID- 24562598
TI  - Pharmacists' perspective on providing care when patients engage in unhealthy
      behaviors.
AB  - OBJECTIVE To assess the association between unhealthy lifestyle-related behaviors
      in patients and the pharmacist's professional obligation for providing care.
      DESIGN Repeated measures ANOVA was used to examine the effect of severity of
      lifestyle disease on professional obligation. SETTING Four live continuing
      education programs on law and management conducted in the state of Florida.
      PARTICIPANTS 488 Florida pharmacists were surveyed with 65% completing the
      survey. MAIN OUTCOME MEASURES Pharmacists' opinions based on lifestyle-related
      diseases classified as follows: low lifestyle-related disease (low LD): nonsmoker
      with asthma who is adherent with asthma medications; moderate (mod) LD: nonsmoker
      with asthma who is nonadherent with asthma medications; high LD: smoker with
      asthma who is adherent with asthma medications. RESULTS The difference between
      the scales for measuring professional obligation for low and mod LD was
      significant, with pharmacists reporting greater professional obligation for low
      versus mod LD. The difference between professional obligation for low and high LD
      was significant, with pharmacists reporting greater professional obligation for
      low than high LD. The difference between professional obligation for mod and high
      LD was significant, with pharmacists reporting a higher professional obligation
      for mod than high LD. CONCLUSION The differences in professional obligation
      between the three patient scenarios were small but statistically significant. The
      findings suggest that certain patient behaviors, such as smoking or medication
      nonadherence, can have a negative effect on pharmacists' sense of professional
      obligation to the patient. 

PMID- 24562591
TI  - Herbal medicines for ischemic stroke: combating inflammation as therapeutic
      targets.
AB  - Stroke is a debilitating disease for which limited therapeutic approaches are
      available currently. Thus, there is an urgent need for developing novel therapies
      for stroke. Astrocytes, endothelial cells and pericytes constitute a
      neurovascular network for metabolic requirement of neurons. During ischemic
      stroke, these cells contribute to post-ischemic inflammation at multiple stages
      of ischemic cascades. Upon ischemia onset, activated resident microglia and
      astrocytes, and infiltrated immune cells release multiple inflammation factors
      including cytokines, chemokines, enzymes, free radicals and other small
      molecules, not only inducing brain damage but affecting brain repair. Recent
      progress indicates that anti-inflammation is an important therapeutic strategy
      for stroke. Given a long history with direct experience in the treatment of human
      subjects, Traditional Chinese Medicine and its related natural compounds are
      recognized as important sources for drug discovery. Last decade, a great progress
      has been made to identify active compounds from herbal medicines with the
      properties of modulating post-ischemic inflammation for neuroprotection. Herein,
      we discuss the inflammatory pathway in early stage and secondary response to
      injured tissues after stroke from initial artery occlusion to brain repair, and
      review the active ingredients from natural products with anti-inflammation and
      neuroprotection effects as therapeutic agents for ischemic stroke. Further
      studies on the post-ischemic inflammatory mechanisms and corresponding drug
      candidates from herbal medicine may lead to the development of novel therapeutic
      strategies in stroke treatment. 

PMID- 24562602
TI  - Surfactant dependent self-organization of Co3O4 nanowires on Ni foam for high
      performance supercapacitors: from nanowire microspheres to nanowire paddy fields.
AB  - Different surfactants were used in a typical hydrothermal process for controlling
      the morphology of the Co3O4 nanowire superstructure on Ni foam. It is easy for
      the Co3O4 nanowires to self-organize into nanowire microspheres on Ni foam in the
      absence of surfactants. And the nanowire microspheres gradually unfold into
      nanowire paddy fields with the addition of nonionic, cationic and anionic
      surfactants, respectively. The results of BET and electrochemical measurements
      show that the specific surface area and capacitance first decrease and then
      increase with the change in the Co3O4 superstructure morphology. Among these
      electrodes, the Co3O4 electrode with paddy like nanowires shows an outstanding
      specific capacitance of 1217.4 F g(-1) and areal specific capacitance as high as
      6087 mF cm(-2) at 0.7 A g(-1) with high mass loading (5 mg cm(-2)), good power
      capability (showing a high specific capacitance of 835.1 F g(-1) (4176 mF cm(-2))
      at 5 A g(-1)), excellent cycling stability and high columbic efficiency (~100%).
      This exceptional performance is benefited from the almost monodispersed nanowire
      morphology and high specific surface area (121.4 m(2) g(-1)). At the same time,
      the asymmetric supercapacitor, employing the Co3O4 electrode with paddy-like
      nanowires as the positive electrode and the activated carbon electrode as the
      negative electrode, was successfully assembled. It shows a high specific energy
      and good long-term electrochemical stability. All these impressive results
      demonstrate that the Co3O4 electrode with paddy-like nanowires is promising for
      practical applications in supercapacitors. 

PMID- 24562599
TI  - Long-term maintenance effect of radiofrequency energy delivery for refractory
      GERD: a decade later.
AB  - BACKGROUND: Patients with gastroesophageal reflux disease (GERD) often seek
      alternative therapy for inadequate symptom control, with over 40% not responding
      to medical treatment. We evaluated the long-term safety, efficacy, and durability
      of response to radiofrequency treatment of the lower esophageal sphincter
      (Stretta). METHODS: Using an intent-to-treat analysis, we prospectively assessed
      217 patients with medically refractory GERD before and after Stretta. There was
      no concurrent control group in the study. Primary outcome measure was
      normalization of GERD-health-related quality of life (GERD-HRQL) in 70% or
      greater of patients at 10 years. Secondary outcomes were 50% reduction or
      elimination of proton pump inhibitors (PPIs) and 60% or greater improvement in
      satisfaction at 10 years. Successful treatment was defined as achievement of
      secondary outcomes in a minimum of 50% of patients. Complications and effect on
      existing comorbidities were evaluated. The results of a 10-year study are
      reported. RESULTS: The primary outcome was achieved in 72% of patients (95%
      confidence interval 65-79). For secondary outcomes, a 50% or greater reduction in
      PPI use occurred in 64% of patients, (41% eliminating PPIs entirely), and a 60%
      or greater increase in satisfaction occurred in 54% of patients. Both secondary
      endpoints were achieved. The most common side effect was short-term chest pain
      (50%). Pre-existing Barrett's metaplasia regressed in 85% of biopsied patients.
      No cases of esophageal cancer occurred. CONCLUSIONS: In this single-group
      evaluation of 217 patients before and after Stretta, GERD-HRQL scores,
      satisfaction, and PPI use significantly improved and results were immediate and
      durable at 10 years.

PMID- 24562603
TI  - Porphyrin-based sensor nanoarchitectonics in diverse physical detection modes.
AB  - Porphyrins and related families of molecules are important organic modules as has
      been reflected in the award of the Nobel Prizes in Chemistry in 1915, 1930, 1961,
      1962, 1965, and 1988 for work on porphyrin-related biological functionalities.
      The porphyrin core can be synthetically modified by introduction of various
      functional groups and other elements, allowing creation of numerous types of
      porphyrin derivatives. This feature makes porphyrins extremely useful molecules
      especially in combination with their other interesting photonic, electronic and
      magnetic properties, which in turn is reflected in their diverse signal input
      output functionalities based on interactions with other molecules and external
      stimuli. Therefore, porphyrins and related macrocycles play a preeminent role in
      sensing applications involving chromophores. In this review, we discuss recent
      developments in porphyrin-based sensing applications in conjunction with the new
      advanced concept of nanoarchitectonics, which creates functional nanostructures
      based on a profound understanding of mutual interactions between the individual
      nanostructures and their arbitrary arrangements. Following a brief explanation of
      the basics of porphyrin chemistry and physics, recent examples in the
      corresponding fields are discussed according to a classification based on
      physical modes of detection including optical detection
      (absorption/photoluminescence spectroscopy and energy and electron transfer
      processes), other spectral modes (circular dichroism, plasmon and nuclear
      magnetic resonance), electronic and electrochemical modes, and other sensing
      modes. 

PMID- 24562605
TI  - Centrifugal LabTube platform for fully automated DNA purification and LAMP
      amplification based on an integrated, low-cost heating system.
AB  - This paper introduces a disposable battery-driven heating system for loop
      mediated isothermal DNA amplification (LAMP) inside a centrifugally-driven DNA
      purification platform (LabTube). We demonstrate LabTube-based fully automated DNA
      purification of as low as 100 cell-equivalents of verotoxin-producing Escherichia
      coli (VTEC) in water, milk and apple juice in a laboratory centrifuge, followed
      by integrated and automated LAMP amplification with a reduction of hands-on time
      from 45 to 1 min. The heating system consists of two parallel SMD thick film
      resistors and a NTC as heating and temperature sensing elements. They are driven
      by a 3 V battery and controlled by a microcontroller. The LAMP reagents are
      stored in the elution chamber and the amplification starts immediately after the
      eluate is purged into the chamber. The LabTube, including a microcontroller-based
      heating system, demonstrates contamination-free and automated sample-to-answer
      nucleic acid testing within a laboratory centrifuge. The heating system can be
      easily parallelized within one LabTube and it is deployable for a variety of
      heating and electrical applications.

PMID- 24562604
TI  - Anticancer activity of structurally related ruthenium(II) cyclopentadienyl
      complexes.
AB  - A set of structurally related Ru(eta(5)-C5H5) complexes with bidentate N,N'
      heteroaromatic ligands have been evaluated as prospective metallodrugs, with
      focus on exploring the uptake and cell death mechanisms and potential cellular
      targets. We have extended these studies to examine the potential of these
      complexes to target cancer cell metabolism, the energetic-related phenotype of
      cancer cells. The observations that these complexes can enter cells, probably
      facilitated by binding to plasma transferrin, and can be retained preferentially
      at the membranes prompted us to explore possible membrane targets involved in
      cancer cell metabolism. Most malignant tumors present the Warburg effect, which
      consists in increasing glycolytic rates with production of lactate, even in the
      presence of oxygen. The reliance of glycolytic cancer cells on trans-plasma
      membrane electron transport (TPMET) systems for their continued survival raises
      the question of their appropriateness as a target for anticancer drug development
      strategies. Considering the interesting findings that some anticancer drugs in
      clinical use are cytotoxic even without entering cells and can inhibit TPMET
      activity, we investigated whether redox enzyme modulation could be a potential
      mechanism of action of antitumor ruthenium complexes. The results from this study
      indicated that ruthenium complexes can inhibit lactate production and TPMET
      activity in a way dependent on the cancer cell aggressiveness and the
      concentration of the complex. Combination approaches that target cell metabolism
      (glycolytic inhibitors) as well as proliferation are needed to successfully cure
      cancer. This study supports the potential use of some of these ruthenium
      complexes as adjuvants of glycolytic inhibitors in the treatment of aggressive
      cancers. 

PMID- 24562609
TI  - Question 1: should a child with neurofibromatosis type 1 be screened for central
      nervous system tumours with neuroimaging?

PMID- 24562606
TI  - Adapting the Group Lifestyle BalanceTM Program for Weight Management Within a
      Large Health Care System Diabetes Education Program.
AB  - PURPOSE: The purpose of this translation study was to evaluate the feasibility
      and effectiveness of an adapted Group Lifestyle Balance (GLB) intervention for
      weight management implemented through an existing diabetes education program
      within a large health care delivery system for overweight/obese individuals with
      diabetes, prediabetes, or neither condition. METHODS: Adults with BMI >= 25 kg/m2
      participated in an adapted GLB intervention designed to be appropriate regardless
      of diabetes status. Effectiveness was based on changes in weight and minutes of
      physical activity between baseline and completion of the 12-week core.
      Differences between subjects based on diabetes status were also examined.
      RESULTS: A total of 111 subjects with diabetes, prediabetes, and no diabetes
      completed baseline survey data and attended at least 9 of the 12 core sessions
      from April 2010 through December 2011. All achieved significant weight loss, and
      the proportion of subjects who reported exercising at least 150 minutes/week
      increased. CONCLUSIONS: The adapted GLB intervention for weight management
      implemented through an existing diabetes education program in a large health care
      system was feasible and effective in the population, regardless of participants'
      diabetes status.

PMID- 24562607
TI  - The Prevalence and Correlates of Mental and Emotional Health Among American
      Indian Adults With Type 2 Diabetes.
AB  - AIMS: The purpose of this study was to examine the prevalence and correlates of
      mental and emotional health factors among a sample of American Indian
      (Indigenous) adults diagnosed with type 2 diabetes. METHODS: Data are from a
      community-based participatory research project involving 2 Indigenous reservation
      communities. Data were collected from 218 Indigenous adults diagnosed with type 2
      diabetes via in-person paper-and-pencil survey interviews. RESULTS: Reports of
      greater numbers of mental/emotional health problems were associated with
      increases in self-reported hyperglycemia, comorbid health problems, and health
      impaired physical activities. CONCLUSIONS: This study addresses a gap in the
      literature by demonstrating the associations between various mental/emotional
      health factors and diabetes-related health problems for Indigenous Americans.
      Findings underscore the importance of holistic, integrated primary care models
      for more effective diabetes care.

PMID- 24562610
TI  - Transcriptional properties and splicing of the flamenco piRNA cluster.
AB  - In Drosophila, the piRNA cluster, flamenco, produces most of the piRNAs (PIWI
      interacting RNAs) that silence transposable elements in the somatic follicle
      cells during oogenesis. These piRNAs are thought to be processed from a long
      single-stranded precursor transcript. Here, we demonstrate that flamenco
      transcription is initiated from an RNA polymerase II promoter containing an
      initiator motif (Inr) and downstream promoter element (DPE) and requires the
      transcription factor, Cubitus interruptus. We show that the flamenco precursor
      transcript undergoes differential alternative splicing to generate diverse RNA
      precursors that are processed to piRNAs. Our data reveal dynamic processing steps
      giving rise to piRNA cluster precursors. 

PMID- 24562611
TI  - Meristem-specific expression of epigenetic regulators safeguards transposon
      silencing in Arabidopsis.
AB  - In plants, transposable elements (TEs) are kept inactive by transcriptional gene
      silencing (TGS). TGS is established and perpetuated by RNA-directed DNA
      methylation (RdDM) and maintenance methylation pathways, respectively. Here, we
      describe a novel RdDM function specific for shoot apical meristems that
      reinforces silencing of TEs during early vegetative growth. In meristems, RdDM
      counteracts drug-induced interference with TGS maintenance and consequently
      prevents TE activation. Simultaneous disturbance of both TGS pathways leads to
      transcriptionally active states of repetitive sequences that are inherited by
      somatic tissues and partially by the progeny. This apical meristem-specific
      mechanism is mediated by increased levels of TGS factors and provides a
      checkpoint for correct epigenetic inheritance during the transition from
      vegetative to reproductive phase and to the next generation. 

PMID- 24562612
TI  - When Mad met Bub.
AB  - The faithful segregation of chromosomes into daughter cells is essential for
      cellular and organismal viability. Errors in this process cause aneuploidy, a
      hallmark of cancer and several congenital diseases. For proper separation,
      chromosomes attach to microtubules of the mitotic spindle via their kinetochores,
      large protein structures assembled on centromeric chromatin. Kinetochores are
      also crucial for a cell cycle feedback mechanism known as the spindle assembly
      checkpoint (SAC). The SAC forces cells to remain in mitosis until all chromosomes
      are properly attached to microtubules. At the beginning of mitosis, the SAC
      proteins--Mad1, Mad2, Bub1, Bub3, BubR1, Mps1, and Cdc20--are recruited to
      kinetochores in a hierarchical and interdependent fashion (Fig 1A). There they
      monitor, in ways that are not fully clarified, the formation of kinetochore
      microtubule attachments. Two studies recently published in EMBO reports by the
      groups of Silke Hauf and Jakob Nilsson, and a recent study by London and Biggins
      in Genes & Development, shed new light on the conserved SAC protein Mad1.

PMID- 24562613
TI  - Ceftazidime/avibactam activity tested against Gram-negative bacteria isolated
      from bloodstream, pneumonia, intra-abdominal and urinary tract infections in US
      medical centres (2012).
AB  - OBJECTIVES: The activity of ceftazidime/avibactam and comparator agents was
      monitored at 73 medical centres across all nine US census bureau regions during
      2012. METHODS: Bacterial isolates were collected from patients hospitalized with
      pneumonia, urinary tract infections (UTI), intra-abdominal infections (IAI) and
      bloodstream infections (BSI). The study protocol predetermined the target numbers
      of strains for each of the requested bacterial species that sites were to
      collect. Isolates were determined to be clinically relevant at the medical centre
      and only one isolate per patient episode was collected. RESULTS: There were 1466
      Gram-negative isolates from BSI, 3245 from pneumonia patients, 501 from IAI and
      2356 from UTI. Ceftazidime/avibactam was active against Enterobacteriaceae from
      each infection type. The MIC90 values for ceftazidime/avibactam against
      Enterobacteriaceae isolates from BSI, pneumonia patients, IAI or UTI were 0.25
      mg/L. The extended-spectrum cephalosporin resistance rates for Escherichia coli
      were 8.5% (UTI), 10.4% (IAI), 12.7% (BSI) and 17.5% (pneumonia patients). The
      extended-spectrum cephalosporin resistance rates for Klebsiella spp. were 13.0%
      (UTI), 13.9% (BSI), 16.3% (IAI) and 19.3% (pneumonia patients). A total of 96.5%
      of the Pseudomonas aeruginosa isolates from BSI, 95.8% from pneumonia patients,
      96.3% from IAI and 98.7% from UTI exhibited a ceftazidime/avibactam MIC of <=8
      mg/L (CLSI susceptible breakpoint for ceftazidime when tested alone against P.
      aeruginosa). Most tested agents showed limited activity against Acinetobacter
      baumannii, except for colistin. A total of 31.2% of A. baumannii displayed
      ceftazidime/avibactam MIC values of <=8 mg/L. CONCLUSIONS: Ceftazidime/avibactam
      demonstrated potent broad-spectrum activity against Gram-negative pathogens
      collected in the USA during 2012 from BSI, pneumonia patients, IAI and UTI.

PMID- 24562614
TI  - Role of inter-species recombination of the ftsI gene in the dissemination of
      altered penicillin-binding-protein-3-mediated resistance in Haemophilus
      influenzae and Haemophilus haemolyticus.
AB  - OBJECTIVES: To screen the ftsI gene sequences obtained from clinical isolates of
      non-typeable Haemophilus influenzae (NTHi) and Haemophilus haemolyticus for the
      presence of mosaic ftsI gene structures, and to evaluate the role of inter
      species recombination of the ftsI gene in the formation and distribution of
      resistant ftsI genes. METHODS: The ftsI genes of 100 Haemophilus isolates
      comprising genetically defined beta-lactamase-negative ampicillin-susceptible
      (gBLNAS), beta-lactamase-positive ampicillin-resistant (gBLPAR), beta-lactamase
      negative ampicillin-resistant (gBLNAR) and beta-lactamase-positive
      amoxicillin/clavulanate-resistant (gBLPACR) isolates of NTHi (n = 50) and H.
      haemolyticus (n = 50) were analysed in this study. Both the flanking regions and
      the full-length ftsI gene sequences of all study isolates were screened for
      mosaic structures using H. influenzae Rd and H. haemolyticus ATCC 33390 as
      reference parental sequences, and bioinformatics methods were used for
      recombination analysis using SimPlot. RESULTS: Of the 100 clinical isolates
      analysed 34% (34/100) harboured mosaic ftsI gene structures containing distinct
      ftsI gene fragments similar to both reference parental sequences. The inter
      species recombination events were exclusively encountered in the ftsI gene of
      gBLNAR/gBLPACR isolates of both NTHi and H. haemolyticus, and were always
      associated with the formation of a mosaic fragment at the 3' end of the ftsI
      gene. There was no evidence supporting horizontal gene transfer (HGT) involving
      the entire ftsI gene among the clinical isolates in vivo. CONCLUSIONS: We provide
      evidence for the HGT and inter-species recombination of the ftsI gene among
      gBLNAR/gBLPACR isolates of NTHi and H. haemolyticus in a clinical setting,
      highlighting the importance of recombination of the ftsI gene in the emergence of
      altered penicillin-binding protein 3 and BLNAR-mediated resistance.

PMID- 24562615
TI  - Molecular epidemiology of Acinetobacter baumannii in Iran: endemic and epidemic
      spread of multiresistant isolates.
AB  - OBJECTIVES: We examined the molecular epidemiology of Acinetobacter baumannii
      clinical isolates from two cities (Tehran and Tabriz) of Iran. METHODS:
      DiversiLab repetitive extragenic palindromic PCR (rep-PCR), multilocus sequence
      typing and sequence group multiplex PCR were performed. The presence of
      resistance mechanisms including metallo-beta-lactamases, extended-spectrum beta
      lactamases, OXA carbapenemases, aminoglycoside-modifying enzymes and RNA
      methylases was also investigated. RESULTS: DiversiLab rep-PCR identified 11
      clusters and 11 singleton isolates. Twelve sequence types (STs), including six
      novel types, were identified. Sequence groups (SGs) 1-3 as well as five
      additional banding patterns were detected by multiplex PCR. A local outbreak in a
      general hospital in Tabriz with an SG1/ST2 profile was identified. Isolates of
      international clone II showed the highest prevalence and the most heterogeneous
      combination of resistance determinants. CONCLUSIONS: Several different
      multiresistant strains of A. baumannii were shown to circulate in Iran. The
      selection and spread of the SG1/ST2 clone might have been favoured by the
      acquisition of resistance genes in the absence of adequate infection control
      measures.

PMID- 24562616
TI  - What causes decreased erythromycin resistance in Streptococcus pyogenes? Dynamics
      of four clones in a southern European region from 2005 to 2012.
AB  - OBJECTIVES: To survey antibiotic resistance among Streptococcus pyogenes isolates
      collected from 2005 to 2012, to characterize those showing erythromycin
      resistance and to analyse the association of certain emm types with erythromycin
      resistance or susceptibility. METHODS: Resistance determinants or mutations
      conferring erythromycin, clindamycin, tetracycline and fluoroquinolone resistance
      were analysed. All erythromycin-resistant isolates and a sample of erythromycin
      susceptible isolates were emm typed. Multilocus sequence typing was performed for
      representative emm types. RESULTS: Antimicrobial susceptibility was studied for
      12 346 S. pyogenes isolates. Erythromycin, clindamycin and tetracycline
      resistance showed a decreasing trend. In 2012, 2.8% of isolates were erythromycin
      resistant versus 7.5% in 2005 and 11.7% in 2006. Although 21 clones were
      involved, 4 clones accounted for almost 90% of erythromycin-resistant isolates.
      The emm12/ST36 clone, carrying the mef(A) gene, was the predominant (41.1%)
      erythromycin-resistant clone, with an incidence peak in 2008, followed by a
      gradual decline. The M phenotype predominated each year except for 2005, when two
      of the main erythromycin-resistant clones (emm11/ST403 and emm28/ST52) harboured
      an erm(B) gene. Erythromycin resistance was significantly higher in adults than
      in children. Skin isolates showed the highest erythromycin resistance rate; among
      these, perianal isolates frequently belonged to the emm28/ST52 clone. The emm
      type was not a predictor of erythromycin resistance; however, most emm11 and
      emm12 were erythromycin-resistant isolates. Macrolide consumption was similar
      throughout the study period. Only two isolates with a high level of levofloxacin
      resistance were detected. CONCLUSIONS: Resistance was mainly related to the
      circulation of emm12/ST36, emm11/ST403, emm28/ST52 and emm4/ST39 clones, all of
      which declined throughout the study period.

PMID- 24562617
TI  - B cell suppression in newborn following treatment of pregnant diffuse large B
      cell lymphoma patient with rituximab containing regimen.
AB  - Non-Hodgkin lymphoma associated with pregnancy is rare. Rituximab based
      chemotherapy is now considered the standard of care and considered safe for the
      treatment of diffuse large B-cell lymphoma (DLBCL) during pregnancy but little is
      known about its safety profile on the fetus. A 32 y primigravida was diagnosed as
      DLBCL at 20 wk of gestation. She received rituximab containing chemotherapy with
      successful pregnancy outcome. Though the baby was absolutely healthy, B-cell was
      totally absent in the cord blood. 

PMID- 24562618
TI  - Factors affecting the association between overall survival and progression-free
      survival in clinical trials of first-line treatment for patients with advanced
      non-small cell lung cancer.
AB  - PURPOSE: New treatment strategies, particularly the introduction of molecular
      targeted agents and appropriate patient selection based on histology and/or
      genotyping, have progressed markedly in recent years, and the overall survival
      (OS) in advanced non-small cell lung cancer (NSCLC) patients has improved. The
      aim of the study was to identify factors affecting longer OS than that estimated
      from progression-free survival (PFS) in first-line treatment for advanced NSCLC.
      METHODS: Sixty-five controlled trials for first-line treatment of advanced NSCLC
      were extracted for the study. Factors influencing higher than predicted OS were
      examined by logistic regression analysis between the OS-extended group and the OS
      association group. RESULTS: PFS was moderately associated with OS. Twenty arms of
      14 trials were categorized as an OS-extended group, in which the ratio of
      observed OS to estimated OS was found to be over 1.2. On multivariate logistic
      regression analysis, number of patients lower than 150, average age younger than
      63 years, and percentage of squamous carcinoma <30 % were found to significantly
      affect this relationship. CONCLUSION: We identified number of patients and well
      known prognostic factors including age and histological cancer type as factors
      influencing longer OS. These factors should be considered for patient
      eligibility, when PFS is used as a surrogate primary endpoint for OS in
      randomized clinical trials of first-line treatment for patients with advanced
      NSCLC.

PMID- 24562619
TI  - The use of mutation-specific antibodies in predicting the effect of EGFR-TKIs in
      patients with non-small-cell lung cancer.
AB  - PURPOSE: We aimed to quantify the epidermal growth factor receptor (EGFR)
      mutation in tumors and to analyze its prediction of EGFR-tyrosine kinase
      inhibitor (EGFR-TKI) treatment efficacy in EGFR mutation-positive non-small-cell
      lung cancer (NSCLC) patients. METHODS: We examined EGFR mutation status in 124
      lung cancer samples by direct sequencing and amplification refractory mutation
      system. Among them, 41 were appropriate to quantify the expression of mutant EGFR
      proteins using immunohistochemistry (IHC) with mutation-specific antibodies. The
      quantification was determined by both the staining intensity and the proportion
      of stained tumor cells. RESULTS: The median progression-free survival (PFS) in
      patients with a high score for mutant EGFR expression was 18.0 months (95 % CI
      16.0-20.0), which was significantly longer than that in patients with a low score
      (8.0 months; 95 % CI 2.6-13.4; P = 0.048). Such significant association with
      patients' PFS was also apparent in the proportion of stained tumor cells (median,
      19.0 vs. 8.0 months; P = 0.019), but not in the staining intensity (P = 0.787).
      Among the 41 specimens, 32 were detected EGFR mutation positive by both direct
      sequencing and ARMS, referring to a relatively high abundance of mutation, and 26
      (81.3 %) of them gained a high expression score of mutant proteins as well. Six
      samples with mutation negative by direct sequencing but positive by ARMS, which
      showed a low abundance, and 5 (83.3 %) of them also revealed a low expression
      score. The EGFR mutation quantitative analysis using mutation-specific IHC was
      moderately consistent with that by molecular-based assays (P = 0.001, kappa value
      0.50). CONCLUSIONS: Our results suggest that immunohistochemical analysis with
      mutation-specific antibodies is a promising approach for quantifying EGFR
      mutations, and may predict the effect of EGFR-TKI treatment for EGFR mutation
      positive NSCLC.

PMID- 24562620
TI  - Proteomic analysis of differential protein expression in platelets of septic
      patients.
AB  - Sepsis is one of the major health problems all over the world. Early diagnostic
      of sepsis is an attractive strategy to decrease the mortality of septic patients.
      However, an effective biomarker that fulfills all the necessary requirements for
      the accurate characterization of sepsis is still unavailable until now. In this
      study, the 2-DE technique followed by mass spectrometry and a database search was
      used for searching and identifying the differential expressed proteins in
      platelets between septic patients and paired healthy controls. Platelet 2-DE
      profiles of septic patients and paired healthy controls with high resolution and
      reproducibility were obtained. Differential platelet 2-DE profiles between septic
      patients and paired healthy controls were established. Differential protein spots
      between normal healthy volunteers and septic patients from platelet 2-DE profiles
      were identified by 2-DE followed with mass spectrometry and a database search.
      Five proteins with increased expression were identified between septic patients
      and healthy controls from platelet samples. These up-expressed proteins were EF
      hand calcium-binding domain-containing protein 7, actin, interleukin-1beta,
      glycoprotein IX, and glycoprotein IIB. Sepsis induces a complex regulation of
      platelet protein changes. Our study highlights the important role of these
      differential expressed proteins in sepsis, which deserve further research as
      potential candidates for therapeutic strategies. Furthermore, our research is
      beneficial for the future developments of sepsis diagnosis and therapy. 

PMID- 24562621
TI  - Effects of Ca2+-activated potassium and inward rectifier potassium channel on the
      differentiation of endothelial progenitor cells from human peripheral blood.
AB  - Endothelial progenitor cells (EPCs) are bone marrow-derived cells that have the
      propensity to differentiate into mature endothelial cells (ECs). The
      transplantation of EPCs has been shown to enhance in vivo postnatal neo
      vasculogenesis, as well as repair infarcted myocardium. Via the whole-cell patch
      clamp technique, numerous types of ion channels have been detected in EPCs,
      including the inward rectifier potassium channel (IKir), Ca2+-activated potassium
      channel (IKCa), and volume-sensitive chloride channel, but their influence on the
      differentiation of EPCs has yet to be characterized. The present study was
      designed to investigate: (1) which ion channels have the most significant impact
      on the differentiation of EPCs; (2) what role ion channels play in the functional
      development of EPCs; (3) the mRNA and protein expression levels of related ion
      channel subunits in EPCs. In our study, EPCs were obtained from the peripheral
      blood of healthy adults and cultured with endothelial growth factors. When EPCs
      differentiate into mature ECs, they lose expression of the stem cell/progenitor
      marker CD133, as analyzed by flow cytometry (0.44+/-0.20 %). However, treatment
      with the potassium channel inhibitor, tetraethylammonium (TEA) results in an
      increase in CD133+ cells (25.50+/-7.55 %). In a functional experiment, we
      observed a reduction in the capacity of TEA treated ECs (differentiated from
      EPCs) to form capillary tubes when seeded in Matrigel. At the mRNA and protein
      levels, we revealed several K+ subtypes, including KCNN4 for IKCa, KCNNMA1 for
      BKCa and Kir3.4 for IKir. These results demonstrate for the first time that
      potassium channels play a significant role in the differentiation of EPCs.
      Moreover, inhibition of potassium channels may depress the differentiation of
      EPCs and the significant potassium channel subunits in EPCs appear to be IKCa,
      BKCa and Kir3.4.

PMID- 24562623
TI  - Allele and genotype frequencies of CYP2B6 in a Turkish population.
AB  - Increasing interest in cytochrome P450 2B6 (CYP2B6) genetic polymorphism was
      stimulated by revelations of a specific CYP2B6 genotype significantly affecting
      the metabolism of various drugs in common clinical use in terms of increasing
      drug efficacy and avoiding adverse drug reactions. The present study aimed to
      determine the frequencies of CYP2B6*4 CYP2B6*5, CYP2B6*6, CYP2B6*7 and CYP2B6*9
      alleles in healthy Turkish individuals (n = 172). Frequencies of three single
      nucleotide polymorphisms were 516G>T (28%), 785A>G (33%), and 1459C>T (12%). The
      frequencies of CYP2B6*1, *4, *5, *6, *7, and *9 alleles were 54.3 (95% CI 49.04
      59.56), 6.4% (95% CI 3.81-8.99), 11% (95% CI 7.69-14.31), 25.3% (95% CI 20.71
      29.89), 0.87% (95% CI -0.11-1.85) and 2.0% (95% CI 0.52-3.48), respectively.
      Allele *6 was more frequent (25.3%) than the other variant alleles in Turkish
      subjects. The frequencies of CYP2B6*4, *5, *6, *7, and *9 alleles were similar to
      European populations but significantly different from that reported for Asian
      populations. This is the first study to document the frequencies of the CYP2B6*4,
      *5, *6, *7, *9 alleles in the healthy Turkish individuals and our results could
      provide clinically useful information on drug metabolism by CYP2B6 in Turkish
      population.

PMID- 24562622
TI  - Ethnic differences in the association of the glutathione S-transferase T1 (GSTT1)
      null genotype and risk of gastric carcinoma: a systematic review and meta
      analysis.
AB  - We performed a systematic review and meta-analysis of the association between the
      glutathione S-transferase T1 (GSTT1) deletion polymorphism and gastric cancer
      risk in populations from different ethnic backgrounds, based on a comprehensive
      literature search of the MEDLINE, EMBASE, and COCHRANE libraries. Thirty-six
      individual case-control studies comprising 7,689 gastric cancer cases and 12,445
      controls were included in our meta-analysis. Overall, the GSTT1 null genotype
      appeared to increase gastric cancer risk (OR 1.17, 95% CI 1.06-1.31, p = 0.003).
      While Caucasian populations showed an association between the GSTT1 deletion
      polymorphism and gastric cancer risk (OR 1.27, 95% CI 1.05-1.52, p = 0.01), Asian
      populations did not show such an association (p = 0.11). When stratified by
      quality assessment scores, a significant association between the GSTT1 deletion
      polymorphism and gastric cancer risk was observed only in the Caucasian high
      quality subgroup (OR 1.27 95% CI 1.01-1.60, p = 0.05). Null genotypes for both
      GSTT1 and GSTM1 deletion polymorphisms also increased gastric cancer risk (OR
      1.37, 95% CI 1.04-1.80, p = 0.03). Our study suggests that the GSTT1 null
      genotype is associated with a significant increase in gastric cancer risk in
      Caucasians, but not in Asians. Further well-designed studies are required to
      confirm the association between GSTT1 polymorphisms and gastric cancer risk in
      relation to various clinicopathological factors in different ethnic groups,
      especially Caucasians.

PMID- 24562624
TI  - Evaluation of reliability on STR typing at leukemic patients used for forensic
      purposes.
AB  - Over the past decades, main advances in the field of molecular biology, coupled
      with benefits in genomic technologies, have led to detailed molecular
      investigations in the genetic diversity generated by researchers. Short tandem
      repeat (STR) loci are polymorphic loci found throughout all eukaryotic genome.
      DNA profiling identification, parental testing and kinship analysis by analysis
      of STR loci have been widely used in forensic sciences since 1993. Malignant
      tissues may sometimes be the source of biological material for forensic analysis,
      including identification of individuals or paternity testing. There are a number
      of studies on microsatellite instability in different types of tumors by
      comparing the STR profiles of malignant and healthy tissues on the same
      individuals. Defects in DNA repair pathways (non-repair or mis-repair) and
      metabolism lead to an accumulation of microsatellite alterations in genomic DNA
      of various cancer types that result genomic instabilities on forensic analyses.
      Common forms of genomic instability are loss of heterozygosity (LOH) and
      microsatellite instability (MSI). In this study, the applicability of autosomal
      STR markers, which are routinely used in forensic analysis, were investigated in
      order to detect genotypes in blood samples collected from leukemic patients to
      estimate the reliability of the results when malignant tissues are used as a
      source of forensic individual identification. Specimens were collected from 90
      acute and 10 chronic leukemia volunteers with oral swabs as well as their paired
      peripheral blood samples from the Oncology Centre of the Department of Hematology
      at Istanbul University, during the years 2010-2011. Specimens were tested and
      compared with 16 somatic STR loci (CSFIPO, THO1, TPOX, vWA, D2S1338, D3S1358,
      D5S818, D7S820, D8S1179, D13S317, D16S539, D18S51, D19S433, D21S11 and FGA)
      widely used in forensic identification and kinship. Only two STR instabilities
      were encountered among 100 specimens. An MSI in the FGA loci and a LOH in the
      D2S1338 loci were determined in two individuals separately. Our results
      demonstrate that the use of the biological samples from leukemia patients in
      forensic identification and kinship testing is questionable, especially if known
      microsatellite instability is available. Genetic instabilities may alter the STR
      polymorphism, leading to potential errors on forensic identification of
      individuals. Therefore, typing of autosomal STRs from leukemia patients should be
      performed with both healthy and malignant tissue samples of individual as
      references. 

PMID- 24562625
TI  - Association of ADAM33 gene polymorphisms with psoriasis in a northeastern Chinese
      population.
AB  - Psoriasis (PS) is a common hyperproliferative and chronic inflammatory disease of
      the skin. It is influenced by both genetic and environmental factors. The ADAM33
      (a disintegrin and metalloproteinase 33) gene located on chromosome 20p13, has
      recently been identified as an asthma-susceptibility gene by positional cloning.
      Recently, ADAM33 has been suspected to be associated with PS. To study the
      association between ADAM33 and PS in the northeastern Chinese population. A total
      of 240 PS patients and a control group of 237 healthy volunteers were recruited
      for this study. Five polymorphic loci (V4, T+1, T2, T1, S2) of ADAM33 were
      selected for genotyping. Genotypes were determined by using the polymerase chain
      reaction-restriction fragment length polymorphism method. We observed the
      frequency of the rs2787094 C allele was significantly higher in cases than in
      controls (50 vs. 33%, P < 0.0001).Similarly, the rs528557 C allele exhibited a
      significantly increased frequency in PS patients compared with healthy controls
      (35 vs. 21%, P < 0.0001). We also found that the frequencies of H3 (CGGAC), H6
      (CGGGG) haplotypes were significantly higher in the case group than in the
      control group (P = 0.006, 0.028, respectively). In contrast, the haplotype H9
      (GAAAG) was more common in the control group than in the case group (P = 0.018).
      Our data suggest that the ADAM33 polymorphisms may be associated with PS in the
      northeastern Chinese population.

PMID- 24562626
TI  - Morphological and molecular genetic variations of oat genotypes grown in
      Kermanshah, Iran.
AB  - Morphological traits and molecular markers are two common methods for genetic
      variation studies. Molecular markers, morphological traits methods and
      relationship between the two were used to study genetic variation among 43 oat
      genotypes and varieties. For this purpose, an augmented design was conducted in
      three replicates at 2008-2009 cropping season in the experimental field of Campus
      of Agriculture and Natural Resources of Razi University, Kermanshah, Iran. Four
      wild oat accessions (Avena sterilis) were added to evaluated genotypes in
      molecular experiment. Results showed a significant variation among genotypes for
      all morphological traits and they were classified based on this variation in four
      groups by WARD cluster analysis. In molecular experiment, 28 inter simple
      sequence repeat (ISSR) primers amplified 206 polymorph bands. Based on Jaccard
      similarity matrix, similarity among genotypes was varied from 0.23 to 0.66 and
      cluster analysis classified genotypes in seven groups by complete linkage method.
      The correlation between ISSR marker and morphological traits classifications was
      not significant. ISSR showed to be a helpful marker for genotype identity and
      separation as it put wild accessions in a group. 

PMID- 24562627
TI  - Gene structure and spatio-temporal expression of chicken LPIN2.
AB  - LPIN2 is one of the members of the Lipin family, which acts as a phosphatidate
      phosphatase enzyme. In this study, we identified the cDNA sequence and exonic
      variants of chicken LPIN2, and evaluated its spatio-temporal expression patterns.
      It indicated that chicken LPIN2 cDNA contained a 2,664-bp open reading frame
      flanked by a 176-bp 5' untranslated region and a 429-bp 3' untranslated region,
      predicted encoding one protein of 886 amino acids. Fourteen variants (three
      missense mutations) were detected from the coding region of chicken LPIN2. W265L
      was predicted to affect the gene function (p < 0.01) and eight synonymous
      mutations were predicted to affect the binding sites of SR proteins, which
      suggested the important functions of these variants. Real-time quantitative PCR
      revealed that LPIN2 in two genotypic chickens (LD and HB chickens, with
      difference in growth rate) presented similar tissue expression patterns, which
      was liver and ovary enriched with low abundance in skeleton muscles. Chicken
      LPIN2 exhibited tissue-specific temporal-expression patterns during postnatal
      development (0-16 weeks). Chicken cutaneous LPIN2 was in steady-state mRNA levels
      during postnatal development; chicken LPIN2 mRNA in pectoralis major had a
      prominent level at 0 week-old, then dropped dramatically at 4 week-old and
      maintained a relatively low level through 4-16 weeks; while chicken hepatic LPIN2
      had a relatively high expression at 0 week-old, with a relatively low level
      through 4-12 weeks and a slight increase at 16 week-old. The studies about the
      basic gene features of chicken LPIN2 would lay the foundation for further
      exploring its biological function.

PMID- 24562628
TI  - Molecular cloning and characterization of a heme oxygenase1 gene from sunflower
      and its expression profiles in salinity acclimation.
AB  - Heme oxygenase1 (HO1) is involved in protecting plants from environmental
      stimuli. In this study, a sunflower (Helianthus annuus L.) HO1 gene (HaHO1) was
      cloned and sequenced. It was confirmed that HaHO1 encodes a precursor protein of
      32.93 kDa with an N-terminal plastid transit peptide which was validated by
      subcellular localization. The amino acid sequence of HaHO1 shared high homology
      with other plant HO1s. The predicted three-dimensional structure showed a high
      degree of structural conservation as compared to the known HO1 crystal
      structures. Phylogenetic analysis revealed that HaHO1 clearly grouped with the
      plant HO1-like sequences. Moreover, the purified recombinant mature HaHO1
      expressed in Escherichia coli exhibits HO activity. Thus, it was concluded that
      HaHO1 encodes a functional HO1 in sunflower. Additionally, HaHO1 gene was
      ubiquitously expressed in all tested tissues, and induced differentially during
      different growth stages after germination, and could be differentially induced by
      several stresses and hemin treatment. For example, a pretreatment with a low
      concentration of NaCl (25 mM) could lead to the induction of HaHO1 gene
      expression and thereafter a salinity acclamatory response. Above cytoprotective
      effect could be impaired by the potent HO1 inhibitor zinc protoporphyrin IX
      (ZnPPIX), which was further rescued by the addition of 50% carbon monoxide
      aqueous solution (in particular) or bilirubin, two catalytic by-products of HO1,
      respectively. Similarly, a HO1 inducer, hemin, could mimic the salinity
      acclamatory response. Together, these findings strongly suggested that the up
      regulation of HaHO1 might be required for the observed salinity acclimation in
      sunflower plants.

PMID- 24562629
TI  - Expression and regulation of pear 1-aminocyclopropane-1-carboxylic acid synthase
      gene (PpACS1a) during fruit ripening, under salicylic acid and indole-3-acetic
      acid treatment, and in diseased fruit.
AB  - In plants, the level of ethylene is determined by the activity of the key enzyme
      1-aminocyclopropane-1-carboxylic acid (ACC) synthase (ACS). A gene encoding an
      ACC synthase protein was isolated from pear (Pyrus pyrifolia). This gene
      designated PpACS1a (GenBank accession no. KC632526) was 1488 bp in length with an
      open reading frame (ORF) encoding a protein of 495 amino acids that shared high
      similarity with other pear ACC synthase proteins. The PpACS1a was grouped into
      type-1 subfamily of plant ACS based on its conserved domain and phylogenetic
      status. Real-time quantitative PCR indicated that PpACS1a was differentially
      expressed in pear tissues and predominantly expressed in anthers. The expression
      signal of PpACS1a was also detected in fruit and leaves, but no signal was
      detected in shoots and petals. Furthermore, the PpACS1a expression was regulated
      during fruit ripening. In addition, the PpACS1a gene expression was regulated by
      salicylic acid (SA) and indole-3-acetic acid (IAA) in fruit. Moreover, the
      expression of the PpACS1a was up-regulated in diseased pear fruit. These results
      indicated that PpACS1a might be involved in fruit ripening and response to SA,
      IAA and disease.

PMID- 24562630
TI  - Delta(9)-Tetrahydrocannabinol treatment during human monocyte differentiation
      reduces macrophage susceptibility to HIV-1 infection.
AB  - The major psychoactive component of marijuana, Delta(9)-tetrahydrocannabinol
      (THC), also acts to suppress inflammatory responses. Receptors for THC, CB1, CB2,
      and GPR55, are differentially expressed on multiple cell types including
      monocytes and macrophages, which are important modulators of inflammation in vivo
      and target cells for HIV-1 infection. Use of recreational and medicinal marijuana
      is increasing, but the consequences of marijuana exposure on HIV-1 infection are
      unclear. Ex vivo studies were designed to investigate effects on HIV-1 infection
      in macrophages exposed to THC during or following differentiation. THC treatment
      of primary human monocytes during differentiation reduced HIV-1 infection of
      subsequent macrophages by replication competent or single cycle CCR5 using
      viruses. In contrast, treatment of macrophages with THC immediately prior to or
      continuously following HIV-1 exposure failed to alter infection. Specific
      receptor agonists indicated that the THC effect during monocyte differentiation
      was mediated primarily through CB2. THC reduced the number of p24 positive cells
      with little to no effect on virus production per infected cell, while
      quantitation of intracellular viral gag pinpointed the THC effect to an early
      event in the viral life cycle. Cells treated during differentiation with THC
      displayed reduced expression of CD14, CD16, and CD163 and donor dependent
      increases in mRNA expression of selected viral restriction factors, suggesting a
      fundamental alteration in phenotype. Ultimately, the mechanism of THC suppression
      of HIV-1 infection was traced to a reduction in cell surface HIV receptor (CD4,
      CCR5 and CXCR4) expression that diminished entry efficiency. 

PMID- 24562631
TI  - Designer adiponectin receptor agonist stabilizes metabolic function and prevents
      brain injury caused by HIV protease inhibitors.
AB  - HIV protease inhibitors (PI) are fundamental to combination antiretroviral
      therapy, which has revolutionized HIV clinical care and produced significant
      reductions in HIV-associated morbidity and mortality. However, PI administration
      is frequently associated with severe metabolic impairment, including
      lipodystrophy, dyslipidemia, and insulin resistance; all of which can contribute
      to cardiovascular and neurologic co-morbidities. Experimental and epidemiological
      data support a potentially important role for the adipokine adiponectin in both
      metabolic and neurologic physiology. This study examined if ADP355, a novel,
      peptide-based adiponectin receptor agonist, could neutralize the detrimental
      effects of PI treatment in experimental animal models. Adult male C57BL/6 mice
      were subjected to a clinically relevant, 4-week regimen of lopinavir/ritonavir,
      with daily injections of ADP355 administered only during the final 2 weeks of PI
      exposure. Comprehensive metabolic, neurobehavioral, and biochemical analyses
      revealed that ADP355 administration partially reversed PI-induced loss of
      subcutaneous adipose tissue, attenuated PI-induced hyperinsulinemia,
      hypertriglyceridemia, and hypoadiponectinemia, and prevented PI-induced cognitive
      impairment and brain injury. Collectively, these data reinforce the link between
      metabolic co-morbidities and cognitive impairment and suggest that
      pharmacological reactivation of adiponectin pathways could remediate key aspects
      of PI-induced metabolic syndrome in clinical settings. Furthermore, therapeutic
      targeting of adiponectin receptors could show utility in reducing the prevalence
      and/or severity of HIV-associated neurocognitive disorders.

PMID- 24562633
TI  - Association of blood pressure with sodium-related knowledge and behaviors in
      adults with hypertension.
AB  - OBJECTIVES To describe sodium-related knowledge and self-reported behaviors in
      adults with hypertension and assess the association between knowledge and
      behaviors and blood pressure levels in this population. METHODS Using convenience
      sampling of patients with hypertension, an oral cross-sectional survey was
      administered by student pharmacists in 45 community pharmacies in Alabama and
      Florida in May to July 2012. After survey questions were administered, patients'
      blood pressures were measured. Data were tested for significance at alpha < 0.05
      using bivariate analyses of independent and dependent variables
      (systolic/diastolic blood pressure [SBP/DBP]) and parallel linear regression of
      significant independent variables. RESULTS The majority of the 664 patients
      surveyed were women (59.3%) and white (75.2%). Most resided in urban areas
      (81.5%). The mean SBP/DBP was 133.3 (SD = 15.7)/81.7 (SD = 9.1) mg Hg. Most
      participants recognized the relationship between salt intake and high blood
      pressure (91.1%) and stroke (78.0%). A small percentage of patients reported that
      they always look for sodium content on food products (15.0%) and always buy low
      sodium products (10.6%). Patients with lower knowledge scores (B = -0.01, P <
      0.001) and those who were advised to cut down on salt (B = 0.02, P = 0.037) had
      higher SBP levels when controlled for gender, race, and awareness of their blood
      pressure goals. In regression analysis, lower knowledge scores were associated
      with increased DBP levels (B = -0.52, P = 0.014) when controlled for gender and
      race. CONCLUSION Many patients were not aware of salt in processed food and did
      not always look for sodium content on nutritional labels. Pharmacists should
      address dietary salt when interacting with patients with hypertension. 

PMID- 24562632
TI  - Multitargeted antiangiogenic tyrosine kinase inhibitors combined to chemotherapy
      in metastatic breast cancer: a systematic review and meta-analysis.
AB  - PURPOSE: We undertook a meta-analysis of randomized trials to evaluate the
      efficacy of multitargeted antiangiogenic tyrosine kinase inhibitors (MATKIs) in
      addition to chemotherapy in metastatic breast cancer. METHODS: PubMed, Web of
      Knowledge databases and the ASCO meeting abstracts were searched for eligible
      literature published up to August 30, 2013. The endpoints included progression
      free survival (PFS), overall survival (OS), overall response rate (ORR) and
      toxicities. Pooled hazard ratios (HRs) for survival outcomes and odds ratio (ORs)
      for dichotomous data with 95 % confidence intervals (CIs) were derived. RESULTS:
      Eight studies including 2,077 participants were analyzed. Compared to
      chemotherapy alone, adding MATKIs to chemotherapy resulted in a 14 % risk
      reduction of PFS events. However, the benefit did not reach statistical
      significance (HR 0.86; 95 % CI 0.70-1.04, P=0.126). Also, no OS benefit was
      observed (HR 1.03; 95 % CI 0.89-1.18, P=0.724). The addition of MATKIs
      significantly increased the ORR (OR 1.57; 95 % CI 1.30-1.91, P=0.000). Subgroup
      analysis revealed that sorafinib showed a significantly greater effect on PFS in
      patients with HER2 negative metastatic breast cancer (HR 0.67; 95 % CI 0.55-0.82,
      P=0.000) in comparison to chemotherapy alone. Additionally, sunitinib seemed to
      have no substantial efficacy for metastatic breast cancer. Toxicities were more
      frequent in patients receiving MATKIs. CONCLUSION: Overall, regimens consisting
      of MATKIs seemed not to be superior to chemotherapy alone in terms of PFS and OS,
      although significant improvement in ORR was observed. However, the addition of
      sorafenib significantly improved PFS. Further studies are needed to corroborate
      this finding.

PMID- 24562635
TI  - What is the appropriate strategy for coronary revascularization in hemodialysis
      patient in Japan?

PMID- 24562634
TI  - A matched-pair comparison of two different locking plates for valgus-producing
      medial open-wedge high tibial osteotomy: peek-carbon composite plate versus
      titanium plate.
AB  - PURPOSE: The first purpose of this study was to compare the clinical and
      radiographic outcome of two different locking plates used for valgus-producing
      medial open-wedge high tibial osteotomy (HTO). The second purpose was to
      histologically evaluate peek-carbon wear for biocompatibility. METHODS: Twenty
      six consecutive patients undergoing open-wedge HTO using the first-generation
      PEEKPower HTO-Plate(r) (Group I) were matched with 26 patients after open-wedge
      HTO with the TomoFixTM plate (Group II). Clinical scores (visual analogue scale
      for pain, WOMAC, Lysholm score) were obtained preoperatively and at a minimum
      follow-up of 24 months postoperatively. Fixation stability was evaluated
      radiographically by comparing the medial proximal tibial angle (MPTA) and tibial
      slope 2 days after open-wedge HTO and after implant removal. Tissue samples of
      Group I were collected at the time of implant removal for histologic evaluation.
      RESULTS: Implant-related complications occurred in 15 % (n = 4) of Group I and 0
      % of Group II. Out of them, 3 implant replacements were excluded from statistical
      analyses. After a final median follow-up of 25 months (range 24-31), the clinical
      scores in both groups showed significant improvements compared to preoperatively
      (visual analogue scale, WOMAC, Lysholm score; p < 0.001), without significant
      group differences (visual analogue scale, n.s.; WOMAC, n.s.; Lysholm score,
      n.s.). No significant differences between baseline and follow-up measurements for
      MPTA and tibial slope were observed within each group (MPTA: Gr. I, n.s.; Gr. II,
      n.s.; tibial slope: Gr. I, n.s.; Gr. II, n.s.) or between the two groups (MPTA,
      n.s.; tibial slope, n.s.). In histologic samples, CF PEEK abrasion did not induce
      inflammation or tissue necrosis. CONCLUSION: The first-generation PEEKPower HTO
      Plate(r) provided a higher rate of implant-related complications compared to the
      TomoFixTM plate at a minimum follow-up of 24 months after valgus-producing open
      wedge HTO. Therefore, it is not recommended to use the first-generation PEEKPower
      HTO-Plate(r) in the clinical practice. LEVEL OF EVIDENCE: III.

PMID- 24562636
TI  - Disease activity is related to acute response to vasodilator in pulmonary artery
      hypertension associated with systemic lupus erythematosus.
AB  - BACKGROUND: No previous study has been done on whether systemic lupus
      erythematosus (SLE) disease activity is related to the hemodynamics and right
      ventricular (RV) function in patients with SLE-associated pulmonary artery
      hypertension (SLE-APAH). METHODS AND RESULTS: This study prospectively recruited
      54 patients (mean age, 32.8+/-8.4 years; 92.6% female) with SLE-APAH, including
      34 patients with SLE disease activity index (SLEDAI) <5 (low score) and 20 with
      SLEDAI >=5 (high score). All patients underwent right heart catheterization and
      iloprost inhalation, and echocardiography was performed before and immediately
      after iloprost inhalation. There was no difference in baseline mean pulmonary
      artery pressure (mPAP) between the 2 groups; pulmonary vascular resistance (PVR)
      was significantly higher and cardiac index was significantly lower in the low
      SLEDAI group. The patients with low SLEDAI had larger RV size and worse RV
      systolic function on echocardiography. After iloprost inhalation, the patients
      with low SLEDAI had a greater decrease in mPAP and PVR than those with high
      SLEDAI, while significantly increased RV systolic function was found only in the
      low-SLEDAI group. CONCLUSIONS: SLE activity is related to hemodynamics and RV
      function in SLE-APAH patients, and those with low SLEDAI might have better acute
      response to vasodilator inhalation.

PMID- 24562637
TI  - Impact of atrial remodeling on the outcome of radiofrequency catheter ablation of
      paroxysmal atrial fibrillation.
AB  - BACKGROUND:  Both the left atrial volume index (LAVI) and estimated total atrial
      conduction time measured using tissue Doppler imaging of the atria (PA-TDI
      duration) are echocardiographic parameters reflecting atrial remodeling. We
      investigated their prognostic value for atrial tachyarrhythmia (AF/AT) recurrence
      after radiofrequency catheter ablation (RFCA) of paroxysmal atrial fibrillation
      (PAF). METHODS AND RESULTS:  We analyzed the data for 100 consecutive patients
      with drug-refractory PAF who underwent RFCA. The correlation between the LAVI and
      PA-TDI was extremely weak (r=0.26, P<0.01). We categorized the patients into 4
      groups based on the median LAVI and PA-TDI duration: group 1 (LAVI <29ml/m(2)/PA
      TDI duration <143ms), group 2 (LAVI >=29ml/m(2)/PA-TDI duration <143ms), group 3
      (LAVI <29ml/m(2)/PA-TDI duration >=143ms), and group 4 (LAVI >=29ml/m(2)/PA-TDI
      duration >=143ms). With a mean follow-up of 20.2+/-8.9 months after a single RFCA
      procedure, 60 patients (60%) were in sinus rhythm without any antiarrhythmic
      drugs. Multivariate analysis using a Cox proportional hazards model demonstrated
      that the group was an independent predictor of AF/AT recurrence after RFCA
      (P=0.0017). The patients in groups 2, 3, and 4 had a 4.0-fold (P=0.048), 6.8-fold
      (P=0.0034) and 10.9-fold (P=0.0001) increase, respectively, in the probability of
      recurrent AF/AT as compared with group 1. CONCLUSIONS:  Preprocedural
      echocardiographic estimation of atrial remodeling was a useful predictor of AF/AT
      recurrence following a single RFCA of PAF. 

PMID- 24562638
TI  - Monitoring the thinning dynamics of soap films by phase shift interferometry. The
      case of perfluoropolyether surfactants.
AB  - An interferometric method to monitor the thinning process of vertical soap films
      from a water solution of surfactant materials is reported. Raw data maps of
      optical path difference introduced by the film are obtained by conventional phase
      shift interferometry. Off-line re-processing of such raw data taking into account
      the layered structure of soap films leads to an accurate measurement of the
      geometrical thickness. As an example of data acquisition and processing, the
      measuring chain is demonstrated on perfluoropolyether surfactants; the section
      profile of vertical films is monitored from drawing to black film state, and
      quantitative data on the dynamics of the thinning process are presented. The
      interferometric method proves effective to the task, and lends itself to further
      investigate the physical properties of soap films. 

PMID- 24562639
TI  - ADHD symptoms and attachment representations: considering the role of conduct
      problems, cognitive deficits and narrative responses in non-attachment-related
      story stems.
AB  - The overall aim of the present study was to investigate ADHD symptoms in relation
      to attachment representations. We used both attachment- and non-attachment
      related story stems, which allowed us to investigate whether problems with
      narrative production can explain the relation between ADHD symptoms and
      attachment representations. We also investigated the role of cognitive deficits
      and conduct problems in these relations. The sample consisted of 89 children (27
      % girls) between 6 and 10 years old, with an oversampling of children with high
      levels of ADHD symptoms. ADHD symptoms and conduct problems were rated by parents
      and teachers. Cognitive functioning was investigated using laboratory tests of
      inhibition, working memory and sustained attention. Attachment representations
      were coded as secure, organized insecure and disorganized categories. Narrative
      responses to non-attachment-related story stems were coded for incoherence and
      negative content. Results showed that children in the disorganized attachment
      category had significantly higher levels of ADHD symptoms compared to those in
      the secure category. Both ADHD symptoms and disorganized attachment were related
      to incoherence and negative content. Attachment representations were not
      associated with ADHD symptoms when controlling for negative content in response
      to non-attachment-related story stems. These results suggest that the
      associations between attachment security and ADHD are yet to be fully understood.
      Importantly, a propensity to envisage negative events seems to characterize
      children with high levels of ADHD symptoms.

PMID- 24562640
TI  - Altered serotonin transporter availability in patients with multiple sclerosis.
AB  - PURPOSE: Modulation of the immune system by the CNS may involve serotonergic
      regulation via the brain serotonin transporters (SERT). This regulation may be
      disturbed in patients with CNS disorders including multiple sclerosis (MS).
      Central serotonergic mechanisms have not been investigated in MS by in vivo
      imaging. The objective of the study was to assess the availability of SERT in
      antidepressant-naive patients with MS by means of PET. METHODS: Included in this
      study were 23 patients with MS and 22 matched healthy volunteers who were
      investigated with PET and the SERT-selective marker [(11)C]DASB, and distribution
      volume ratios were determined. Clinical assessment of the patients included the
      expanded disability status scale, the MS fatigue scale Wurzburger
      Erschopfungsinventar bei MS (WEIMuS) and the Beck Depression Inventory (BDI). The
      PET data were analysed with both volume-of-interest and voxel-based analyses to
      determine regional SERT availability. RESULTS: Patients had lower SERT
      availability in the cingulate cortex, the thalamus and the insula, and increased
      availability in the orbitofrontal cortex. Patients with relapsing/remitting MS
      tended to have lower SERT in the hippocampus, whereas patients with primary
      progressive disease showed increased SERT availability in prefrontal regions.
      There was a positive correlation between SERT availability in the insula and both
      depression and fatigue scores (r = 0.56 vs. BDI, p = 0.02; r = 0.49 vs. WEIMuS, p
      = 0.05). CONCLUSION: Serotonergic neurotransmission in MS patients is altered in
      limbic and paralimbic regions as well as in the frontal cortex that this appears
      to contribute to psychiatric symptoms of MS.

PMID- 24562641
TI  - FDG PET during radiochemotherapy is predictive of outcome at 1 year in non-small
      cell lung cancer patients: a prospective multicentre study (RTEP2).
AB  - PURPOSE: To assess prospectively the prognostic value of FDG PET/CT during
      curative-intent radiotherapy (RT) with or without concomitant chemotherapy in
      patients with non-small-cell lung cancer (NSCLC). METHODS: Patients with
      histological proof of invasive localized NSCLC and evaluable tumour, and who were
      candidates for curative-intent radiochemotherapy (RCT) or RT were preincluded
      after providing written informed consent. Definitive inclusion was conditional
      upon significant FDG uptake before RT (PET1). All included patients had a FDG
      PET/CT scan during RT (PET2, mean dose 43 Gy) and were evaluated by FDG PET/CT at
      3 months and 1 year after RT. The main endpoint was death (from whatever cause)
      or tumour progression at 1 year. RESULTS: Of 77 patients preincluded, 52 were
      evaluable. Among the evaluable patients, 77% received RT with induction
      chemotherapy and 73% RT with concomitant chemotherapy. At 1 year, 40 patients (77
      %) had died or had tumour progression. No statistically significant association
      was found between stage (IIIB vs. other), histology (squamous cell carcinoma vs.
      other), induction or concomitant chemotherapy, and death/tumour progression at 1
      year. The SUVmax in the PET2 scan was the single variable predictive of death or
      tumour progression at 1 year (odds ratio 1.97, 95% CI 1.25 - 3.09, p = 0.003) in
      multivariate analysis. The area under the receiver operating characteristic curve
      was 0.85 (95% CI 0.73 - 0.94, p < 10(-4)). A SUVmax value of 5.3 in the PET2 scan
      yielded a sensitivity of 70% and a specificity of 92% for predicting tumour
      progression or death at 1 year. CONCLUSION: This prospective multicentre study
      demonstrated the prognostic value in terms of disease-free survival of SUVmax
      assessed during the 5th week of curative-intent RT or RCT in NSCLC patients
      (NCT01261598; RTEP2 study).

PMID- 24562642
TI  - Staging the axilla in breast cancer patients with 18F-FDG PET: how small are the
      metastases that we can detect with new generation clinical PET systems?
AB  - PURPOSE: Point spread function (PSF) reconstruction improves spatial resolution
      throughout the entire field of view of a PET system and can detect smaller
      metastatic deposits than conventional algorithms such as OSEM. We assessed the
      impact of PSF reconstruction on quantitative values and diagnostic accuracy for
      axillary staging of breast cancer patients, compared with an OSEM reconstruction,
      with emphasis on the size of nodal metastases. METHODS: This was a prospective
      study in a single referral centre in which 50 patients underwent an (18)F-FDG PET
      examination before axillary lymph node dissection. PET data were reconstructed
      with an OSEM algorithm and PSF reconstruction, analysed blindly and validated by
      a pathologist who measured the largest nodal metastasis per axilla. This size was
      used to evaluate PET diagnostic performance. RESULTS: On pathology, 34 patients
      (68%) had nodal involvement. Overall, the median size of the largest nodal
      metastasis per axilla was 7 mm (range 0.5 - 40 mm). PSF reconstruction detected
      more involved nodes than OSEM reconstruction (p = 0.003). The mean PSF to OSEM
      SUVmax ratio was 1.66 (95 % CI 1.01 - 2.32). The sensitivities of PSF and OSEM
      reconstructions were, respectively, 96% and 92% in patients with a largest nodal
      metastasis of >7 mm, 60% and 40% in patients with a largest nodal metastasis of
      <=7 mm, and 92% and 69% in patients with a primary tumour <=30 mm. Biggerstaff
      graphical comparison showed that globally PSF reconstruction was superior to OSEM
      reconstruction. The median sizes of the largest nodal metastasis in patients with
      nodal involvement not detected by either PSF or OSEM reconstruction, detected by
      PSF but not by OSEM reconstruction and detected by both reconstructions were 3, 6
      and 16 mm (p = 0.0064) respectively. In patients with nodal involvement detected
      by PSF reconstruction but not by OSEM reconstruction, the smallest detectable
      metastasis was 1.8 mm. CONCLUSION: As a result of better activity recovery, PET
      with PSF reconstruction performed better than PET with OSEM reconstruction in
      detecting nodal metastases <=7 mm. However, its sensitivity is still insufficient
      for it to replace surgical approaches for axillary staging. PET with PSF
      reconstruction could be used to perform sentinel node biopsy more safely in
      patients with a primary tumour <=30 mm and with unremarkable PET results in the
      axilla.

PMID- 24562644
TI  - 18F-FDG PET/CT findings in uterine leiomyomas.

PMID- 24562643
TI  - Prognostic value of 18F-DOPA PET/CT at the time of recurrence in patients
      affected by neuroblastoma.
AB  - PURPOSE: The aim of this study was to investigate the relationship between (123)I
      metaiodobenzylguanidine (MIBG) scan semi-quantification and a new (18)F-DOPA
      positron emission tomography (PET)/CT score in patients with suspected or
      documented neuroblastoma (NB) relapse and to assess the association between these
      two parameters and progression-free survival (PFS)/overall survival (OS).
      METHODS: We analysed 24 NB patients who had undergone (123)I-MIBG and (18)F-DOPA
      PET/CT scans at the time of suspected relapse, after applying a proper scoring
      system for each scan. In time-to-event analyses, the score distributions were
      regarded as continuous and were categorized in tertiles and medians. We used
      Kaplan-Meier curves and Cox proportional hazard models for PFS and OS in order to
      estimate the independent prognostic impact of (123)I-MIBG and (18)F-DOPA PET/CT
      scans. RESULTS: The (123)I-MIBG and (18)F-DOPA scores were highly and positively
      correlated (Spearman's rho = 0.8, p < 0.001). Over a median follow-up of 14
      months (range 6-82), 12 cases of disease progression and 6 deaths occurred.
      Multivariate Cox models showed a higher risk of disease progression [hazard ratio
      (HR) 17.0, 95% confidence interval (CI) 2.7-109] in NB patients with (123)I-MIBG
      score > 3 (3rd tertile) and an even higher risk (HR:37.2, 95% CI 2.4-574) in
      those with (18)F-DOPA whole-body metabolic burden (WBMB) >7.5 (median), after
      adjustment for all main clinical/pathological factors considered. Kaplan-Meier
      analyses showed a significant association with OS (log-rank p = 0.01 and p = 0.03
      for (123)I-MIBG and (18)F-DOPA WBMB, respectively). CONCLUSION: Our results
      confirm the good agreement between (18)F-DOPA PET/CT and (123)I-MIBG scan in
      patients affected by NB relapse. In time-to-event analyses, (123)I-MIBG scan and
      (18)F-DOPA PET/CT scores were independently and significantly associated with
      disease progression.

PMID- 24562645
TI  - FDG PET/CT in autoimmune pancreatitis.

PMID- 24562646
TI  - Longitudinal monitoring of tumor antiangiogenic therapy with near-infrared
      fluorophore-labeled agents targeted to integrin alphavbeta3 and vascular
      endothelial growth factor.
AB  - PURPOSE: Optical imaging is emerging as a powerful tool for the noninvasive
      imaging of the biological processes in living subjects. This study aimed to
      investigate whether optical imaging of integrin alphavbeta3 and vascular
      endothelial growth factor (VEGF) expression can serve as sensitive biomarkers for
      tumor early response to antiangiogenic therapy. METHODS: We synthesized two near
      infrared fluorescence (NIRF) imaging agents, CF680R-3PRGD2 and CF750-BevF(ab')2,
      which were designed to specifically bind to integrin alphavbeta3 and VEGF,
      respectively. The ability of optical imaging using the two imaging agents for
      early monitoring the antiangiogenic effect of sunitinib was evaluated. RESULTS:
      CF680R-3PRGD2 and CF750-BevF(ab')2 specifically bound to their respective targets
      in vitro and in HT-29 tumor-bearing nude mice. Sunitinib treatment led to
      significantly decreased tumor uptake of CF680R-3PRGD2 (e.g., 7.47 +/- 1.62 % vs.
      4.24 +/- 0.16 % on day 4; P < 0.05) and CF750-BevF(ab')2 (e.g., 7.43 +/- 2.43 %
      vs. 4.04 +/- 1.39 % on day 2; P < 0.05) in vivo. Immunofluorescence staining and
      an enzyme-linked immunosorbent assay confirmed that sunitinib-induced changes in
      tumor uptake of CF680R-3PRGD2 and CF750-BevF(ab')2 were correlated with changes
      in the levels of integrin alphavbeta3 and VEGF. Radiobiodistribution of (99m)Tc
      3PRGD2 and (125)I-BevF(ab')2, the radiocounterparts of CF680R-3PRGD2 and CF750
      BevF(ab')2, respectively, also validated optical imaging results. CONCLUSION:
      Longitudinal monitoring of tumor integrin alphavbeta3 and VEGF expression could
      be used as early biomarkers for tumor response to antiangiogenic therapy. This
      strategy may facilitate the development of new antiangiogenic drugs, and be used
      for elucidation of the underlying mechanisms of therapies involving the integrin
      and the VEGF signaling pathway.

PMID- 24562647
TI  - Factors affecting intrapatient liver and mediastinal blood pool 18F-FDG
      standardized uptake value changes during ABVD chemotherapy in Hodgkin's lymphoma.
AB  - PURPOSE: The aim of our study was to assess the intrapatient variability of 2
      deoxy-2-((18)F)-fluoro-D-glucose ((18)F-FDG) uptake in the liver and in the
      mediastinum among patients with Hodgkin's lymphoma (HL) treated with doxorubicin
      (Adriamycin), bleomycin, vinblastine and dacarbazine (ABVD) chemotherapy (CHT).
      METHODS: The study included 68 patients (30 men, 38 women; mean age 32 +/- 11
      years) with biopsy-proven HL. According to Ann Arbor criteria, 6 were stage I, 34
      were stage II, 12 were stage 3 and 16 were stage 4. All of them underwent a
      baseline (PET0) and an interim (PET2) (18)F-FDG whole-body positron emission
      tomography (PET)/CT. All patients were treated after PET0 with two ABVD cycles
      for 2 months that ended 15 +/- 5 days prior to the PET2 examination. All patients
      were further evaluated 15 +/- 6 days after four additional ABVD cycles (PET6).
      None of the patients presented a serum glucose level higher than 107 mg/dl. The
      mean and maximum standardized uptake values (SUV) of the liver and mediastinum
      were calculated using the same standard protocol for PET0, PET2 and PET6,
      respectively. Data were examined by means of the Wilcoxon matched pairs test and
      linear regression analysis. RESULTS: The main results of our study were an
      increased liver SUVmean in PET2 (1.76 +/- 0.35) as compared with that of PET0
      (1.57 +/- 0.31; p < 0.0001) and PET6 (1.69 +/- 0.28; p = 0.0407). The same
      results were obtained when considering liver SUVmax in PET2 (3.13 +/- 0.67) as
      compared with that of PET0 (2.82 +/- 0.64; p < 0.0001) and PET6 (2.96 +/- 0.52; p
      = 0.0105). No significant differences were obtained when comparing mediastinum
      SUVmean and SUVmax in PET0, PET2 and PET6 (p > 0.05). Another finding is a
      relationship in PET0 between liver SUVmean and SUVmax with the stage, which was
      lower in those patients with advanced disease (r (2) = 0.1456 and p = 0.0013 for
      SUVmean and r (2) = 0.1277 and p = 0.0028 for SUVmax). CONCLUSION: The results of
      our study suggest that liver (18)F-FDG uptake is variable in patients with HL
      during the CHT treatment and the disease course and should be considered
      carefully when used to define the response to therapy in the interim PET in HL.

PMID- 24562649
TI  - Treatment outcomes of patients with cervical cancer with complete metabolic
      responses after definitive chemoradiotherapy.
AB  - PURPOSE: We sought to evaluate failure patterns and prognostic factors predictive
      of recurrences and survival in cervical cancer patients who are treated with
      definitive chemoradiotherapy (ChRT), who have a subsequent complete metabolic
      response (CMR) with (18) F-fluorodeoxyglucose positron-emission tomography (FDG
      PET) after treatment. METHODS: The records of 152 cervical cancer patients who
      were treated with definitive chemoradiotherapy were evaluated. All patients
      underwent pre-treatment positron emission tomography (PET-CT), and post-treatment
      PET-CT was performed within a median of 3.9 months (range, 3.0-9.8 months) after
      the completion of ChRT. The prognoses of partial response/progressive disease
      (PR/PD) cases (30 patients, 18 %) and CMR cases (122 patients, %82) were
      evaluated. Univariate and multivariate analysis effecting the treatment outcome
      was performed in CMR cases. RESULTS: The median follow-ups for all patients and
      surviving patients were 28.7 (range, 3.3-78.7 months) and 33.2 months (range,
      6.23-78.7 months), respectively. Four-year overall survival (OS) rate was
      significantly better in patients with CMR compared to patients with PR/PD (66.9 %
      vs. 12.4 %, p < 0.001, respectively). Patients with PR/PD had higher maximum
      standardized uptake value (SUVmax) of primary cervical tumor (26.4 +/- 10.1 vs.
      15.9 +/- 6.3; p < 0.001) and larger tumor (6.4 cm +/- 2.3 cm vs. 5.0 cm +/- 1.4
      cm; p < 0.001) compared to patients with CMR. Of the 122 patients with post
      treatment CMRs, 25 (21 %) developed local, locoregional, or distant failure. In
      univariate analysis, tumor size >= 5 cm, 'International Federation of
      Obstetricians and Gynecologists' (FIGO) stage >= IIB, and pelvic and/or para
      aortic lymph node metastasis were predictive of both overall survival (OS) and
      disease-free survival (DFS), while histology was predictive of only OS. In
      multivariate analysis, tumor size, stage and lymph node metastasis were
      predictive of OS and DFS. CONCLUSION: Although CMR is associated with better
      outcomes, relapses remain problematic, especially in patients with bulky tumors
      (>= 5 cm), extensive stage (>= IIB) or pelvic and/or para-aortic lymph node
      metastasis. These findings could support the need for more aggressive treatment
      or adjuvant chemotherapy regimens.

PMID- 24562648
TI  - Thymidine phosphorylase influences [(18)F]fluorothymidine uptake in cancer cells
      and patients with non-small cell lung cancer.
AB  - PURPOSE: Thymidine phosphorylase (TP), a key enzyme in the pyrimidine nucleoside
      salvage pathway, catalyses the reversible phosphorylation of thymidine, thereby
      generating thymine and 2-deoxy-D-ribose-1-phosphate. By regulating the levels of
      endogenous thymidine, TP may influence [(18)F]fluorothymidine ([(18)F]FLT)
      uptake. We investigated the effect of TP activity on [(18)F]FLT uptake by
      tumours. METHODS: Uptake of [(3)H]FLT and [(3)H]thymidine ([(3)H]Thd) and the
      activities of TP, thymidine kinase 1 (TK1), and equilibrative nucleoside
      transporter 1 (ENT1) were determined in exponentially growing A431, A549, HT29,
      HOP92, ACHN, and SKOV3 cells in the presence or absence of tipiracil
      hydrochloride, a TP inhibitor. Eighty-five non-small cell lung cancer tissues
      from a patient cohort that was previously studied with [(18)F]FLT positron
      emission tomography (PET) were retrieved and subjected to immunohistochemical
      analysis of TP expression. Factors that affected the maximum standardised uptake
      value (SUVmax) of [(18)F]FLT-PET were identified by multiple linear regression
      analysis. RESULTS: A431 cells had the highest TP activity; A549 and HT29 cells
      had moderate TP activity; and ACHN, SKOV3, and HOP92 cells had little detectable
      TP activity. Cell lines with high TP activity took up more [(3)H]FLT than
      [(3)H]Thd, whereas cells with little TP activity took up more [(3)H]Thd than
      [(3)H]FLT. In cells with high TP activity, TP inhibition decreased [(3)H]FLT
      uptake and increased [(3)H]Thd uptake. However, TP inhibition had no effect on
      ACHN, SKOV3, and HOP92 cells. TP inhibition did not change TK1 or ENT1 activity,
      but did increase the intracellular level of thymidine. The SUVmax of [(18)F]FLT
      was affected by three independent factors: Ki-67 expression (P < 0.001),
      immunohistochemical TP score (P < 0.001), and tumour size (P = 0.015).
      CONCLUSIONS: TP activity influences [(18)F]FLT uptake, and may explain
      preferential uptake of [(18)F]FLT over [(3)H]Thd. These results provide important
      insights into the biology of [(18)F]FLT as a proliferation marker.

PMID- 24562650
TI  - PET/CT studies of multiple myeloma using (18) F-FDG and (18) F-NaF: comparison of
      distribution patterns and tracers' pharmacokinetics.
AB  - OBJECTIVE: The aim of this prospective study is to evaluate the combined use of
      fluorine-18 fluorodeoxyglucose ((18) F-FDG) and fluorine-18 sodium fluoride ((18)
      F-NaF) PET/CT in the skeletal assessment of patients with multiple myeloma (MM)
      and to compare the efficacy of these two PET tracers regarding detection of
      myeloma-indicative osseous lesions. PATIENTS AND METHODS: The study includes 60
      patients with multiple myeloma (MM) diagnosed according to standard criteria. All
      patients underwent dynamic (dPET/CT) scanning of the pelvis as well as whole body
      PET/CT studies with both tracers. The interval between the two exams was one day.
      Sites of focal increased (18) F-FDG uptake were considered as highly suspicious
      of myelomatous involvement. The lesions detected on the (18) F-NaF PET/CT scans
      were then correlated with those detected on (18) F-FDG PET/CT, which served as a
      reference. Moreover, the (18) F-FDG PET/CT results were also correlated with the
      low-dose CT findings. The evaluation of dPET/CT studies was based on qualitative
      evaluation, SUV calculation, and quantitative analysis based on a 2-tissue
      compartment model and a non-compartmental approach. RESULTS: Whole body (18) F
      FDG PET/CT revealed approximately 343 focal lesions while (18) F-NaF PET/CT
      revealed 135 MM-indicative lesions (39 % correlation). CT demonstrated 150
      lesions that correlated with those in (18) F-FDG PET/CT (44 % correlation). Six
      patients demonstrated a diffuse pattern of disease with (18) F-FDG, while 15 of
      them had a mixed (diffuse and focal) pattern of skeletal (18) F-FDG uptake. A
      high number of degenerative, traumatic and arthritic disease lesions were
      detected with (18) F-NaF PET/CT. In three patients with multiple focal (18) F-FDG
      uptake, (18) F-NaF PET/CT failed to demonstrate any bone lesion. The dPET/CT
      scanning of the pelvic area with (18) F-FDG and (18) F-NaF revealed 77 and 24 MM
      indicative lesions, respectively. Kinetic analysis of (18) F-FDG revealed the
      following mean values: SUVaver = 5.1, k1 = 0.37 (1/min), k3 = 0.10 (1/min), VB =
      0.06, influx = 0.04 (1/min), FD = 1.28; the respective values for (18) F-NaF were
      SUVaverage = 10.7, k1 = 0.25 (1/min), k3 = 0.34 (1/min), VB = 0.02, influx = 0.10
      (1/min), FD = 1.37. Apart from the correlation between VB of (18) F-FDG and k1 of
      (18) F-NaF (r = 0.54), no other significant correlation was observed between the
      two tracers' kinetic parameters. We found a significant correlation between FD
      and SUVaverage (r = 0.93), FD and SUVmax (r = 0.80), FD and influx ( r = 0.85),
      as well as between influx and SUVaverage (r = 0.74) for (18) F-FDG. In (18) F-NaF
      we observed the most significant correlations between FD and SUVaverage (r =
      0.97), FD and SUVmax (r = 0.87), and between influx and k1 (r = 0.72).
      CONCLUSION: The combined use of (18) F-FDG PET/CT and (18) F-NaF PET/CT provides
      different molecular information regarding the biological processes that take
      place in a MM osseous lesion. (18) F-FDG PET/CT proved to be a more specific
      biomarker than (18) F-NaF PET/CT in multiple myeloma skeletal assessment.

PMID- 24562652
TI  - Enhancement of muscle repair using human mesenchymal stem cells with a magnetic
      targeting system in a subchronic muscle injury model.
AB  - BACKGROUND: A magnetic cell targeting system was previously developed to promote
      the accumulation of transplanted cells in sites of injury in order to effectively
      treat injured tissues. However, the optimum time of exposure to the magnetic
      field and the strength of the magnetic force have not yet been clarified. In this
      study, we investigated the optimum conditions of the magnetic force required to
      retain iron-labeled human mesenchymal stem cells (hMSCs) at the site of
      transplantation for muscle repair in a subchronic skeletal muscle injury nude rat
      model. METHODS: First, the optimum strength and time of exposure to the magnetic
      force for cell retention at the transplantation site were investigated 2 days
      after cell transplantation (1 * 10(5) cells). Second, the degree of enhancement
      of muscle repair was investigated at 3 weeks after cell transplantation in the
      group treated without a magnetic force and two typical magnetic condition groups
      that exhibited different levels of cell integration in first part of the study.
      RESULTS: On the basis of the results of the first investigation, it was concluded
      that a magnetic strength of 1.5 T and 10 min of exposure to the magnetic force
      were efficient conditions to induce the retention of transplanted cells at the
      site of transplantation. In the second study, the groups exposed to a 1.5-T
      magnetic field for 10 min demonstrated significant enhancement of muscle repair,
      both histologically and electromechanically. CONCLUSIONS: This study identified
      the optimal conditions required to retain transplanted hMSCs at the site of
      transplantation using a magnetic targeting system. This study also showed that
      the restoration of subchronic muscle injuries can be enhanced by magnetically
      labeled hMSCs following the application of a magnetic force.

PMID- 24562651
TI  - Prospective evaluation of (68)Ga-DOTANOC PET-CT in differentiated thyroid cancer
      patients with raised thyroglobulin and negative (131)I-whole body scan:
      comparison with (18)F-FDG PET-CT.
AB  - PURPOSE: The purpose of the study was to evaluate the role of (68)Ga-DOTANOC PET
      CT in differentiated thyroid cancer (DTC) patients with negative (131)I-whole
      body scan (WBS) along with serially increasing serum thyroglobulin (Tg), and
      compare the same with (18)F-FDG PET-CT. METHODS: Sixty two DTC patients with
      serially rising Tg levels and negative (131)I-WBS were prospectively enrolled.
      All patients underwent (68)Ga-DOTANOC PET-CT and (18)F-FDG PET-CT within an
      interval of two weeks. PET-CT analysis was done on a per-patient basis, location
      wise and lesion wise. All PET-CT lesions were divided into four categories-local,
      nodal, pulmonary and skeletal. Histopathology and/or serial serum Tg level,
      clinical and imaging follow up (minimum-1 year) were used as a reference
      standard. RESULTS: Ga-DOTANOC PET-CT demonstrated disease in 40/62 (65 %)
      patients and (18)F-FDG PET-CT in 45/62 (72 %) patients, with no significant
      difference on McNemar analysis (p = 0.226). Per-patient sensitivity and
      specificity of (68)Ga-DOTANOC PET-CT was 78.4 %, 100 %, and for (18)F-FDG PET-CT
      was 86.3 %, 90.9 %, respectively. Out of 186 lesions detected by both PET-CTs,
      121/186 (65 %) lesions were seen on (68)Ga-DOTANOC PET-CT and 168/186 (90.3 %)
      lesions on (18)F-FDG PET-CT (p < 0.0001). There were 103/186 (55 %) lesions
      concordant on both. Excellent agreement was noted between (68)Ga-DOTANOC PET-CT
      and (18)F-FDG PET-CT for detection of local disease (K = 0.92), while moderate
      agreement was noted for nodal and pulmonary disease (K = 0.67). (68)Ga-DOTANOC
      PET-CT changed management in 21/62 (34 %) patients and (18)F-FDG PET-CT in 17/62
      (27 %) patients. CONCLUSION: Ga-DOTANOC PET-CT is inferior to (18)F-FDG PET-CT on
      lesion based but not on patient based analysis for detection of
      recurrent/residual disease in DTC patients with negative WBS scan and elevated
      serum Tg levels. It can also help in selection of potential candidates for
      peptide receptor radionuclide therapy.

PMID- 24562653
TI  - Entrapment of the dorsal sensory branch of the ulnar nerve by circumferential
      extraneural lipoma.

PMID- 24562654
TI  - An electronic structure perspective of graphene interfaces.
AB  - The unusual electronic structure of graphene characterized by linear energy
      dispersion of bands adjacent to the Fermi level underpins its remarkable
      transport properties. However, for practical device integration, graphene will
      need to be interfaced with other materials: 2D layered structures, metals (as ad
      atoms, nanoparticles, extended surfaces, and patterned metamaterial geometries),
      dielectrics, organics, or hybrid structures that in turn are constituted from
      various inorganic or organic components. The structural complexity at these
      nanoscale interfaces holds much promise for manifestation of novel emergent
      phenomena and provides a means to modulate the electronic structure of graphene.
      In this feature article, we review the modifications to the electronic structure
      of graphene induced upon interfacing with disparate types of materials with an
      emphasis on iterative learnings from theoretical calculations and electronic
      spectroscopy (X-ray absorption fine structure (XAFS) spectroscopy, scanning
      transmission X-ray microscopy (STXM), angle-resolved photoemission spectroscopy
      (ARPES), and X-ray magnetic circular dichroism (XMCD)). We discuss approaches for
      engineering and modulating a bandgap in graphene through interfacial
      hybridization, outline experimental methods for examining electronic structure at
      interfaces, and overview device implications of engineered interfaces. A unified
      view of how geometric and electronic structure are correlated at interfaces will
      provide a rational means for designing heterostructures exhibiting emergent
      physical phenomena with implications for plasmonics, photonics, spintronics, and
      engineered polymer and metal matrix composites. 

PMID- 24562665
TI  - Azaporphine guest-host complexes in solution and gas-phase: evidence for
      partially filled nanoprisms and exchange reactions.
AB  - Supramolecular guest-host complexes comprising various azaporphines stacked in a
      coordination nanoprism consisting of tris(4-pyridyl)triazines as panels, 1,4
      bis(pyridyl)benzenes as pillars and (en)Pd as hinges were synthesized according
      to the procedure of Fujita and coworkers and characterized as ions in the gas
      phase by high-resolution electrospray ionization mass spectrometry and collision
      induced dissociation as well as in solution by analytical ultracentrifugation.
      Apart from fully filled nanoprisms we have also prepared and observed partially
      filled as well as empty congeners in aqueous solutions. Upon mixing room
      temperature solutions of two types of nanoprisms, we observe that azaporphine
      guest exchange reactions occur on a timescale of minutes, indicating that the
      formation of the guest-host complexes is reversible. 

PMID- 24562664
TI  - Supraorbital and supratrochlear stimulation for trigeminal autonomic
      cephalalgias.
AB  - Trigeminal autonomic cephalalgias (TAC) is a rare primary headache disorder with
      challenging and limited treatment options for those unfortunate patients with
      severe and refractory pain. This article will review the conventional
      pharmacologic treatments as well as the new neuromodulation techniques designed
      to offer alternative and less invasive treatments. These techniques have evolved
      from the treatment of migraine headache, a much more common headache syndrome,
      and expanded towards application in patients with TAC. Specifically, the article
      will discuss the targeting of the supratrochlear and supraorbital nerves, both
      terminal branches of the trigeminal nerve. 

PMID- 24562673
TI  - Acute renal failure in tetanus: correspondence.

PMID- 24562672
TI  - Thymidylate synthase protein expression levels remain stable during paclitaxel
      and carboplatin treatment in non-small cell lung cancer.
AB  - BACKGROUND: Thymidylate synthase (TS) is a potential predictive marker for
      efficacy of treatment with pemetrexed. The current study aimed at investigating
      whether TS expression changes during non-pemetrexed chemotherapy of non-small
      cell lung cancer (NSCLC), thus making rebiopsy necessary for deciding on
      pemetrexed second-line treatment. MATERIALS AND METHODS: TS immunohistochemistry
      was performed on biopsies and available resection specimens from 65 NSCLC
      patients stage T1-3N0-2 treated with preoperative carboplatin and paclitaxel
      [neoadjuvant chemotherapy (NAC)-group] and from 53 NSCLC patients stage T1-4N0-1
      treated with surgery without preceding chemotherapy [operation (OP)-group] that
      served as controls. The diagnostic biopsies and subsequent resection samples were
      compared in order to evaluate for change in TS expression in groups treated with
      and without preoperative chemotherapy. RESULTS: No statistically significant
      change in TS expression was observed between diagnostic biopsies and subsequent
      surgical resections of primary tumors in either the OP-group (p = 0.186) or the
      NAC-group (p = 0.542). Primary tumors were discordant between diagnostic biopsies
      and resection specimens when TS expression was dichotomized into high (H score >=
      150) and low (H score < 150), in 45 and 33% in the OP-group and NAC-group,
      respectively (p = 0.288). The fraction of tumors which increased (19 vs. 20%; p =
      0.900) and decreased (42 vs. 23%; p = 0.095) in TS expression was equal between
      the OP- and the NAC-group. CONCLUSION: The discordance observed between paired
      serial samples likely reflects intratumoral heterogeneity of TS expression and
      highlights the need of sufficient representative material for TS expression
      analysis if this biomarker is to be used for treatment selection. TS expression
      in primary tumors remained unchanged, and new biopsies for deciding on second
      line pemetrexed does not seem warranted based on the current results.

PMID- 24562675
TI  - Relationship between intrinsic cardiac autonomic ganglionated plexi and the
      atrial fibrillation nest.
AB  - BACKGROUND:  Spectral analysis of the left atrium can identify high dominant
      frequency (DF) sites, which might play a role in the perpetuation of atrial
      fibrillation (AF). Furthermore, the role of the cardiac autonomic nervous system
      (CANS) in the genesis of AF has been demonstrated. The relationship between CANS
      and the high-DF sites (AF nest) was the aim of the investigation. METHODS AND
      RESULTS:  In 12 dogs, high frequency stimulation was applied to locate 4 major
      left atrial (LA) ganglionated plexi (GPs). An Ensite Array and a mapping catheter
      were delivered into the left atrium for electroanatomical mapping. During sinus
      rhythm, spectral analysis was performed on the bipolar electrograms in the left
      atrium before and after epicardial GP ablation. The majority of AF nests were
      close to the GPs (52+/-18% of total AF nests). After GP ablation, the mean LA DF
      values decreased from 54+/-7Hz to 49+/-4Hz (P=0.023), and DF values of the AF
      nest decreased from 93+/-2Hz to 87+/-4Hz (P=0.001). Most of the previous AF nest
      sites close to the GPs disappeared (85+/-23%). The surface area of the AF nest
      decreased from 9+/-5cm(2) to 3+/-2cm(2) (P=0.001). CONCLUSIONS:  Catheter
      ablation of the GP decreased the DF values, AF nest areas and diminished the
      number of AF nests; particularly those close to the GPs, indicating that the CANS
      might play an important role in the mechanism of the AF nest. 

PMID- 24562674
TI  - Enhanced resistance to UV-B radiation in Anabaena sp. PCC 7120 (Cyanophyceae) by
      repeated exposure.
AB  - In natural habitats, organisms especially phytoplankton are not always
      continuously subjected to ultraviolet-B radiation (UVBR). By simulation of the
      natural situation, the N2-fixing cyanobacterium Anabaena sp. PCC 7120 was
      subjected to UV-B exposure and recovery cycles. A series of morphological and
      physiological changes were observed in Anabaena sp. PCC 7120 under repeated UVBR
      when compared with controls. Such as the breakage of filaments, intervals between
      heterocysts, heterocyst frequency, total carbohydrate, and carotenoids were
      increased, while the nitrogenase activity and photosynthetic activity were
      inhibited by repeated UVBR; however, these activities could recover when UV-B
      stress was removed. Unexpectedly, the over-compensatory growth was observed at
      the end of the second round of exposure and recovery cycle. Our results showed
      that discontinuous UVBR could increase the growth rate and the tolerance as well
      as repair capacity of Anabaena sp. PCC 7120. These results indicate that moderate
      UVBR may increase the growth of cyanobacteria in natural habitats.

PMID- 24562676
TI  - Augmentation index does not reflect risk of coronary artery disease in elderly
      patients.
AB  - BACKGROUND: Augmentation index (AI) has been used as a clinical index of arterial
      stiffness and has been reported to be an independent predictor of cardiovascular
      events, but some investigators have reported that AI is not a useful marker to
      identify coronary artery disease (CAD) in elderly patients. The majority of CAD
      patients are elderly people, therefore the aim of this study was to examine
      whether AI is a useful marker to identify the risk of CAD. METHODS AND RESULTS: A
      total of 120 patients (69+/-10 years of age; 83 male) who underwent cardiac
      catheterization for suspected CAD were enrolled. Invasive central blood pressure
      (BP) was measured using a fluid-filled catheter. Non-invasive AI was calculated
      by the SphygmoCor (AtCor Medical) system at the end of catheterization. Subjects
      consisted of 99 patients with CAD and 21 patients without CAD. There was no
      significant difference in AI between the CAD and the non-CAD groups (24+/-10 vs.
      24+/-14%). Non-invasive systolic central BP was lower than the invasive systolic
      central BP (115+/-18 vs. 130+/-23 mmHg, P<0.001) in all patients. Non-invasive
      diastolic central BP was greater than the invasive diastolic central BP (67+/-10
      vs. 63+/-10 mmHg, P<0.001). CONCLUSIONS: In elderly patients, AI may not be a
      useful marker to identify CAD.

PMID- 24562678
TI  - Contact pressure-aided spectroscopy.
AB  - Contact pressure induced by manually operated fiber optic probes can
      significantly affect the optical properties of the studied tissue. If the contact
      pressure and the changes in optical properties are measured properly, then the
      complementary information can be used to obtain additional insight into the
      tissue physiology. However, as reliable assessment of the contact pressure in the
      existing diffuse reflectance setups is difficult, the impact of contact pressure
      is usually neglected or considered as a source of errors. We introduce a
      measurement system for controlled application of contact pressure and for the
      acquisition of diffuse reflectance spectra, which is suitable for in vivo studies
      and for overcoming the limitations of the existing measurement setups. A spectral
      contact-pressure plane is proposed to present the combined information,
      highlighting the unique tissue response to the applied pressure.

PMID- 24562680
TI  - Isolation and characterization of polymorphic microsatellites in the genome of
      yak (Bos grunniens).
AB  - The researches on yak genetics and breeding were extremely restricted due to
      lacking of reliable DNA molecular markers. The microsatellites with repeat motif
      (AC)n/(GT)n in yak genome were enriched by Dynal magnetic beads and the gene
      libraries containing (AC)n/(GT)n were constructed. Among the 92 identified and
      sequenced positive clones, 40 contained perfect repeats (43.48%), 41 contained
      imperfect repeats (44.57%) and 11 contained compound repeats (11.96%). As
      compared with the percentage of perfect repeats, no significant increases of
      imperfect repeats were observed in yak genome, which indicated that the level of
      adaptive evolution of the ability to repair damaged genomic DNA for yaks were
      high enough to endure the natural pressure of nucleotide substitution resulted
      from ultraviolet irradiation in high-altitude areas. Totally 19 polymorphic
      microsatellite loci were screened and genotyped on the basis of electropherograms
      on an ABI 310 Genetic Analyzer. All the loci exhibited moderate to high-level
      polymorphisms in a test population of Bos grunniens and the polymorphic
      information content ranged from 0.299 to 0.861 (mean 0.678). The newly isolated
      (AC)n/(GT)n repeats from yak genome will display their potential values in
      examining intra-population genetic structure and inter-population relationships,
      and also in investigating molecular markers for production and adaptive traits of
      individual/population.

PMID- 24562682
TI  - Comprehensive genetic discrimination of Leonurus cardiaca populations by AFLP,
      ISSR, RAPD and IRAP molecular markers.
AB  - Leonurus cardiaca is well known for its medicinal importance. In this
      investigation, genotypic characterization of this species from six eco
      geographical regions of Iran was evaluated by four molecular techniques (AFLP,
      RAPD, ISSR and IRAP). A total of 899 polymorphic fragments were detected by used
      molecular markers (AFLP = 356, RAPD = 325, ISSR = 113 and IRAP = 105) with an
      overall average polymorphism of 81.24%. Genetic variation calculated using
      Shannon's Information index (I) and Nei's gene diversity index (H) showed high
      genetic diversity in studied germplasm. Also, analysis of molecular variance
      showed high genetic variation among (55%) and within populations (45%). UPGMA
      dendrogram constructed from combined data of molecular markers distinguished
      studied populations in accordance with the results obtained by each marker which
      all individuals were clearly differentiated into two major clusters. The
      correlation coefficients were statistically significant for all marker systems
      with the highest correlation between similarity matrixes of RAPD and ISSR markers
      (r = 0.82). The present results have an important implication for L. cardiaca
      germplasm characterization, improvement, and conservation. Furthermore, the
      characterized individuals exhibited a great deal of molecular variation and they
      seem to have a rich gene pool for breeding programs.

PMID- 24562681
TI  - Genetic association studies of endothelial nitric oxide synthase gene
      polymorphisms in women with unexplained recurrent pregnancy loss: a systematic
      and meta-analysis.
AB  - Recurrent pregnancy loss (RPL) is a multifactorial disorder, both genetic and
      environmental factors contribute to the development of RPL. Recently, the
      association between endothelial nitric oxide synthase (eNOS) gene polymorphisms
      and unexplained recurrent pregnancy loss (URPL) has been reported, and the
      results were inconsistent. Hence, we performed the meta-analysis to drive a more
      precise estimation of association between eNOS polymorphisms and URPL. Odds ratio
      (OR) and its 95% confidence interval were calculated under co-dominant (AA vs.
      BB, TT vs. GG) and additive (A vs. B, T vs. G) genetic models. Studies of eNOS
      intron 4 VNTR and Glu298Asp were separated by ethnicities. 13 studies included
      1,769 URPL cases and 1,376 healthy controls on eNOS intron 4 VNTR polymorphism,
      and 11 studies were involved in Glu298Asp polymorphism with 1,498 URPL cases and
      1,123 healthy controls. The integrated results showed that eNOS Glu298Asp
      polymorphism was associated with URPL [ORs were 1.91 (1.42-2.56), P < 0.001; 1.67
      (1.36-2.04), P < 0.001, respectively]. When analyses were separated by ethnic
      subgroups, the association between eNOS Glu298Asp polymorphism and URPL was only
      observed in East Asians [OR = 1.88 (1.52-2.33), P < 0.001 under additive model],
      and there was no association between eNOS intron 4 VNTR polymorphism and URPL in
      Caucasians and East Asians. The results indicated a significant association
      between eNOS Glu298Asp polymorphism and URPL in East Asians. No association was
      observed between eNOS intron 4 VNTR polymorphism and URPL in Caucasians and East
      Asians.

PMID- 24562677
TI  - The heart as an endocrine organ.
AB  - The concept of the heart as an endocrine organ arises from the observation that
      the atrial cardiomyocytes in the mammalian heart display a phenotype that is
      partly that of endocrine cells. Investigations carried out between 1971 and 1983
      characterised, by virtue of its natriuretic properties, a polypeptide referred to
      atrial natriuretic factor (ANF). Another polypeptide isolated from brain in 1988,
      brain natriuretic peptide (BNP), was subsequently characterised as a second
      hormone produced by the mammalian heart atria. These peptides were associated
      with the maintenance of extracellular fluid volume and blood pressure. Later work
      demonstrated a plethora of other properties for ANF and BNP, now designated
      cardiac natriuretic peptides (cNPs). In addition to the cNPs, other polypeptide
      hormones are expressed in the heart that likely act upon the myocardium in a
      paracrine or autocrine fashion. These include the C-type natriuretic peptide,
      adrenomedullin, proadrenomedullin N-terminal peptide and endothelin-1. Expression
      and secretion of ANF and BNP are increased in various cardiovascular pathologies
      and their levels in blood are used in the diagnosis and prognosis of
      cardiovascular disease. In addition, therapeutic uses for these peptides or
      related substances have been found. In all, the discovery of the endocrine heart
      provided a shift from the classical functional paradigm of the heart that
      regarded this organ solely as a blood pump to one that regards this organ as self
      regulating its workload humorally and that also influences the function of
      several other organs that control cardiovascular function. 

PMID- 24562685
TI  - Perspectives on active ageing and work-related stress in Europe: a European
      opinion poll.

PMID- 24562686
TI  - Rene Magritte, Golconda 1953.

PMID- 24562683
TI  - Activation of GRs-Akt-nNOs-NR2B signaling pathway by second dose GR agonist
      contributes to exacerbated hyperalgesia in a rat model of radicular pain.
AB  - Central Akt, neuronal nitric oxide synthase (nNOS) and N-methyl-D-aspartate
      receptor subunit 2B (NR2B) play key roles in the development of neuropathic pain.
      Here we investigate the effects of glucocorticoid receptors (GRs) on the
      expression and activation of spinal Akt, nNOS and NR2B after chronic compression
      of dorsal root ganglia (CCD). Thermal hyperalgesia test and mechanical allodynia
      test were used to measure rats after intrathecal injection of GR antagonist
      mifepristone or GR agonist dexamethasone for 21 days postoperatively. Expression
      of spinal Akt, nNOS, NR2B and their phosphorylation state after CCD was examined
      by western blot. The effects of intrathecal treatment with dexamethasone or
      mifepristone on nociceptive behaviors and the corresponding expression of Akt,
      nNOS and NR2B in spinal cord were also investigated. Intrathecal injection of
      mifepristone or dexamethasone inhibited PWMT and PWTL in CCD rats. However,
      hyperalgesia was induced by intrathecal injection of dexamethasone on days 12 to
      14 after surgery. Treatment of dexamethasone increased the expression and
      phosphorylation levels of spinal Akt, nNOS, GR and NR2B time dependently, whereas
      administration of mifepristone downregulated the expression of these proteins
      significantly. GRs activated spinal Akt-nNOS/NR2B pathway play important roles in
      the development of neuropathic pain in a time-dependent manner.

PMID- 24562687
TI  - Vestibular assessment: a practical approach.
AB  - This paper presents an evidence-based introduction to assessing and managing the
      dizzy patient. It is based upon a literature review highlighting current best
      practice and the clinical experience of the author. Dizziness is common, often
      chronic and largely untreated, resulting in great personal and economic loss.
      Serious pathological causes of dizziness may be quickly and effectively screened
      by a simple ocular motor examination, differentiating these from peripheral
      vestibular lesions. A triage, differentiating dizziness into either acute onset,
      intermittent episodes or continuous symptoms is proposed, along with management
      strategies for the commonest causes of dizziness. Vestibular suppressant
      medication should be restricted to the acute phase of a vestibular episode.
      Vestibular rehabilitation therapy is the most effective treatment for continuous
      or chronic dizziness. 

PMID- 24562689
TI  - PHQ-9.

PMID- 24562690
TI  - Acute invasive small-bowel Anisakiasis: clinical and CT findings in 19 patients.
AB  - PURPOSE: To evaluate the clinical and CT findings in patients with small-bowel
      Anisakiasis. MATERIALS AND METHODS: Nineteen patients with small-bowel
      Anisakiasis and who underwent abdominal CT between 2005 and 2012 were enrolled in
      our study. All of these patients were diagnosed using either a serologic test for
      Anisakiasis (n = 18) or by pathology (n = 1). Their medical records were reviewed
      in order to determine the clinical findings. CT images were retrospectively
      reviewed by two radiologists to evaluate the characteristics of the involved
      bowel wall and the ancillary findings. RESULTS: All patients had presented with
      the acute onset of severe abdominal pain as well as a history of having recently
      eaten raw fish. The mean time interval from eating the fish to the onset of
      abdominal pain was 1.7 days. Eighteen patients were treated conservatively and
      experienced resolution of their symptoms within seven days of hospitalization.
      One patient underwent surgical exploration for presumed small-bowel ischemia. The
      sites of involvement included the ileum (16/19, 84%) and jejunum (3/19, 16%). All
      patients had circumferential bowel-wall thickening (mean, 0.8 cm) with an
      intermediate length of involved bowel (mean, 7.9 cm). Small-bowel obstruction
      occurred in 16 patients (84%). The target sign was present in 17 patients (89%),
      ascites, particularly in the perilesional area, in 16 patients (84%), and
      mesenteric edema in 15 patients (79%). CONCLUSION: Small-bowel Anisakiasis should
      be considered in the differential diagnosis of acute abdomen in order to avoid
      unnecessary surgery when patients present with abdominal pain after having
      recently eaten raw fish, concentric bowel-wall thickening with the target sign in
      the ileum, perilesional ascites, as well as bowel obstruction seen on CT.

PMID- 24562692
TI  - Accessing epigenetic variation in the plant methylome.
AB  - Cytosine DNA methylation is the addition of a methyl group to the 5' position of
      a cytosine, which plays a crucial role in plant development and gene silencing.
      Genome-wide profiling of DNA methylation is now possible using various techniques
      and strategies. Using these technologies, we are beginning to elucidate the
      extent and impact of variation in DNA methylation between individuals and/or
      tissues. Here, we review the different techniques used to analyze the methylomes
      at the whole-genome level and their applications to better understand epigenetic
      variations in plants. 

PMID- 24562695
TI  - Discovery of potential anti-inflammatory drugs: diaryl-1,2,4-triazoles bearing N
      hydroxyurea moiety as dual inhibitors of cyclooxygenase-2 and 5-lipoxygenase.
AB  - A series of hybrids from diaryl-1,2,4-triazole and hydroxamic acid or N
      hydroxyurea were synthesized and evaluated as novel anti-inflammatory agents. The
      biological data showed that (i) all the compounds showed dual COX-2/5-LOX
      inhibitory activities in vitro, and 15e showed optimal inhibitory activities (COX
      2: IC50 = 0.15 MUM, 5-LOX: IC50 = 0.85 MUM), (ii) 15e selectively inhibited COX-2
      relative to COX-1 with selectivity index (SI = 0.012) comparable to celecoxib (SI
      = 0.015), (iii) 15e exhibited potent anti-inflammatory activity (inhibition:
      54.1%) which was comparable to the reference drug celecoxib (inhibition: 46.7%)
      in a xylene-induced ear edema assay, and (iv) 15e displayed promising analgesic
      activity in acetic acid-induced writhing response and hot-plate assay. Finally, a
      molecular modeling study revealed the binding interactions of 15e with COX-2 and
      5-LOX. Our findings suggest that 15e may be a promising anti-inflammatory agent
      for further evaluation.

PMID- 24562693
TI  - Age related differences of executive functioning problems in everyday life of
      children and adolescents in the autism spectrum.
AB  - Numerous studies investigated executive functioning (EF) problems in people with
      autism spectrum disorders (ASD) using laboratory EF tasks. As laboratory task
      performances often differ from real life observations, the current study focused
      on EF in everyday life of 118 children and adolescents with ASD (6-18 years). We
      investigated age-related and individual differences in EF problems as reported by
      parents on the Behavioral Rating Inventory Executive Functions (BRIEF: Gioia et
      al. in Behavior rating inventory of executive function. Psychological Assessment
      Resources, Odesse 2000), and examined the association with autism severity.
      Inhibition problems were mostly found in the youngest group (6- to 8-year-olds),
      whereas problems with planning where more evident for 12- to 14-year-olds as
      compared to 9- to 11-year-olds. In a subsample of participants meeting the ADOS
      ASD cut-off criteria the age related differences in planning were absent, while
      problems with cognitive flexibility were less apparent in 15- to 18-year-olds,
      compared to 9- to 11-, and 12- to 14-year olds. EF problems surpassing the
      clinical cutoff were only observed in 20% (planning) to 51% (cognitive
      flexibility) of the children and adolescents, and no relation was found with ASD
      symptom severity. This underlines the heterogeneous nature of ASD.

PMID- 24562696
TI  - Rolimeter measurements are suitable as substitutes to stress radiographs in the
      evaluation of posterior knee laxity.
AB  - PURPOSE: The quantification of posterior knee laxity is crucial in the evaluation
      of injuries to the posterior cruciate ligament (PCL) as it has important
      implications to the treatment for these injuries. The objective of this study was
      to compare the test results of stress radiography and instrumented drawer testing
      (Rolimeter) for the assessment of posterior knee laxity in patients with PCL
      injury. METHODS: In 45 patients with an injury to the PCL, lateral radiographs of
      both knees were obtained under anterior and posterior tibial load (150 N) using a
      standardized approach. Patients with injury of the ACL to either knee were
      excluded from the study. During the same clinic visit, an instrumented
      measurement of anterior-posterior knee laxity was performed at 90 degrees  of
      knee flexion by an experienced examiner using the Rolimeter device. The mean side
      to-side differences (SSD) of both (radiographic and instrumented) measurements
      were compared to each other, and the correlation was calculated using the Pearson
      coefficient. RESULTS: The SSD (affected/healthy side) of posterior translation
      determined from the radiographs was 8.2 +/- 3.2 mm, and the SSD of the
      instrumented measurement testing was 7.6 +/- 3.2 mm. The mean difference between
      radiographic and Rolimeter test results was 1.8 +/- 1.5 mm. The Pearson's
      correlation coefficient revealed a good correlation between both measurements of
      0.74. CONCLUSIONS: It may be suggested by the results of this study that under
      the absence of an ACL injury and a fixed posterior drawer sign, the Rolimeter is
      a suitable tool to assess the posterior laxity of the knee in the clinical
      setting. Its advantages are the absence of radiation to the patient, its
      availability, and the low cost. Therefore, the Rolimeter device may serve as a
      valuable alternative to stress radiography in the evaluation of PCL-injured
      patients. LEVEL OF EVIDENCE: II.

PMID- 24562697
TI  - Cold-induced vasoconstriction may persist long after cooling ends: an evaluation
      of multiple cryotherapy units.
AB  - PURPOSE: Localized cooling is widely used in treating soft tissue injuries by
      modulating swelling, pain, and inflammation. One of the primary outcomes of
      localized cooling is vasoconstriction within the underlying skin. It is thought
      that in some instances, cryotherapy may be causative of tissue necrosis and
      neuropathy via cold-induced ischaemia leading to nonfreezing cold injury (NFCI).
      The purpose of this study is to quantify the magnitude and persistence of
      vasoconstriction associated with cryotherapy. METHODS: Data are presented from
      testing with four different FDA approved cryotherapy devices. Blood perfusion and
      skin temperature were measured at multiple anatomical sites during baseline,
      active cooling, and passive rewarming periods. RESULTS: Local cutaneous blood
      perfusion was depressed in response to cooling the skin surface with all devices,
      including the DonJoy (DJO, p = 2.6 * 10(-8)), Polar Care 300 (PC300, p = 1.1 *
      10(-3)), Polar Care 500 Lite (PC500L, p = 0.010), and DeRoyal T505 (DR505, p =
      0.016). During the rewarming period, parasitic heat gain from the underlying
      tissues and the environment resulted in increased temperatures of the skin and
      pad for all devices, but blood perfusion did not change significantly, DJO
      (n.s.), PC300 (n.s.), PC500L (n.s.), and DR505 (n.s.). CONCLUSIONS: The results
      demonstrate that cryotherapy can create a deep state of vasoconstriction in the
      local area of treatment. In the absence of independent stimulation, the condition
      of reduced blood flow persists long after cooling is stopped and local
      temperatures have rewarmed towards the normal range, indicating that the
      maintenance of vasoconstriction is not directly dependent on the continuing
      existence of a cold state. The depressed blood flow may dispose tissue to NFCI.

PMID- 24562698
TI  - T2-mapping at 3 T after microfracture in the treatment of osteochondral defects
      of the talus at an average follow-up of 8 years.
AB  - PURPOSE: To compare repaired cartilage with native cartilage, and inter-observer
      reliability, using T2 mapping at 3 T for assessing cartilage repair in
      osteochondral defects of the talus after the microfracture technique. METHODS: We
      enrolled eight females and seven males undergoing arthroscopic microfracture for
      osteochondral defects of the talus at an average follow-up of 7.9 +/- 2.2 years
      (range 5-13 years). Cartilage tissue was assessed using a 3-T magnetic resonance
      imaging unit with an 8-channel phased array foot and ankle coil (gradient
      strength, 50 mT/m; slew rate, 200 T/m/s). T2 maps were then calculated. Three
      independent boarded specialists evaluated the images, and magnetic resonance
      observation of cartilage repair tissue scores was used to assess the cartilage
      and joint status. Clinical results were assessed using the Hannover Scoring
      System (HSS) for the ankle and the American Orthopaedic Foot and Ankle Society
      (AOFAS) hind-foot score. RESULTS: No significant mean differences were found
      between the T2 properties of the repair tissue and those of the native reference
      cartilage (T2 = 38.6 +/- 5.3 ms, range 30.2-55.8 ms vs. 40.3 +/- 8.5 ms, range
      31.4-59.8 ms, respectively; intra-class correlation coefficient = 0.94;
      confidence interval 0.84-0.99, P <= 0.001). Despite >=50 % defect filling in all
      patients, subchondral bone changes were considerable. The HSS at the follow-up
      revealed a mean score of 87 +/- 12 (range 51-97), and the AOFAS-Score was 90 +/-
      13 (range 59-100). CONCLUSIONS: 3 T T2 maps were similar in repaired and native
      cartilage with good inter-observer reliability. LEVEL OF EVIDENCE: IV.

PMID- 24562699
TI  - Prevention of the surface resorption of bone grafts by topical application of
      bisphosphonate on different carrier materials.
AB  - OBJECTIVE: The hypothesis of the present study was that topically applied
      bisphosphonate (BP) on a collagen membrane or alternatively bovine bone mineral
      prevents surface resorption of onlay bone grafts. MATERIAL AND METHODS: In eight
      adult pigs, bone blocks were harvested bilaterally from the mandible and fixed to
      the lateral cortex of the horizontal ramus to simulate a ridge augmentation. In a
      split-mouth study design, we used alendronate in aqueous solution (1 mg/ml) on
      the test-side in three different ways: on a collagen membrane (Bio-Gide(r)),
      soaked in bovine bone mineral granules (Bio-Oss(r)), or applied to the bone graft
      directly. The same materials without BP were used as controls on the
      contralateral side. After 3 months, the animals were sacrificed. The evaluation
      included sequential fluorochromic labeling and measurement of bone height in
      microradiography and toluidine blue staining. RESULTS: In five cases, necrosis of
      the overlying periosteal tissues with BP was observed macroscopically. A
      statistically significantly lower loss in graft height was seen on the test-side
      for Bio-Gide(r) + alendronate (0.65 %) versus Bio-Gide(r) (1.52 %), p = 0.002;
      Bio-Oss(r) + alendronate (1.16 %) versus Bio-Oss(r) (4.20 %), p = 0.001; and bone
      graft + alendronate (1.25 %) versus bone graft alone (6.01 %), p = 0.006. An
      inhibitory effect on bone remodeling was observed by a statistically
      significantly lower number of resorption lacunae. CONCLUSION: The hypothesis was
      accepted that a bisphosphonate-treated membrane reduced bone graft resorption;
      however, periosteal necrosis requires better adaptation of the dosage. CLINICAL
      RELEVANCE: A bisphosphonate membrane could be a helpful tool to preserve
      augmentation height of onlay bone grafts.

PMID- 24562701
TI  - [Cancer screening in transition].

PMID- 24562700
TI  - Early wound healing and patient morbidity after single-incision vs. trap-door
      graft harvesting from the palate--a clinical study.
AB  - OBJECTIVES: The aim of this study is to compare wound healing and patient pain
      perception of single-incision (single-incision, modified single-incision) and
      trap-door surgical techniques to harvest subepithelial connective tissue grafts
      from the palate. MATERIAL AND METHODS: Thirty-six patients were selected for root
      coverage procedures with subepithelial connective tissue grafts and randomly
      assigned to two single-incision groups or a trap-door group (n = 12/group). One
      week after surgery, a modified early-wound healing index (EHI), patient pain and
      painkiller intake were recorded. Follow-up was performed until complete
      epithelialization was achieved. RESULTS: Single-incision techniques showed
      significantly improved early healing over trap-door approaches. Specifically, the
      mean EHI was 2.50 +/- 1.14 for single-incision techniques, as compared to 3.33 +/
      1.30 for trap door. The incidence of secondary healing was significantly lower
      in the single-incision groups. Concomitantly, the cumulative dosage and duration
      of painkiller intake were significantly reduced, as compared to the trap-door
      group. CONCLUSION: Within the limits of this trial, single-incision techniques
      can lead to improved early healing and reduced patient pain after subepithelial
      connective tissue graft harvesting than trap-door techniques. CLINICAL RELEVANCE:
      Avoiding trap-door incisions for harvesting of connective tissue grafts may
      reduce patient morbidity.

PMID- 24562702
TI  - [Early detection of cancer in the German National Cancer Plan: health policy and
      legal regulations].
AB  - The "Law on the Further Development of the Early Detection of Cancer and Quality
      Assurance Through Clinical Cancer Registries" implements key recommendations of
      the German National Cancer Plan. The central objectives of the law are to improve
      the access, effectiveness, and quality of the existing cancer screening programs.
      It creates the necessary legal framework to turn the current opportunistic
      cervical cancer screening and colorectal cancer screening into population-based
      quality assured programs in accordance with the European guidelines for quality
      assurance in cancer screening. Each person in the eligible target population will
      receive a personal invitation letter with a view to increase the take-up rate of
      the screening program. Furthermore, there will be comprehensive quality assurance
      measures and evaluation activities. The law also stipulates that cancer registry
      data must be used for quality assurance purposes and the monitoring of the cancer
      screening programs. Special emphasis is put on the provision of balanced and
      unbiased information on the potential benefits and harms of the screening
      program. This is to ensure that the decision for or against participating in a
      screening program is based on an informed choice. Thus, German health policy is
      taking a clear stance against pushing take-up rates uncritically. This position
      is a paradigm shift of fundamental importance. The Federal Joint Committee - the
      highest decision-making body of the so-called joint self-government of
      physicians, dentists, hospitals, and statutory health insurance funds in Germany 
      is responsible for defining explicitly the details of the screening programs
      within 3 years.

PMID- 24562703
TI  - [Early detection of cervical cancer in Germany: evidence and implementation].
AB  - Cervical cancer is the third most common cancer among women worldwide, with an
      estimated 529,000 new cases in 2008. The incidence of cervical cancer in Germany
      is still among the highest in Western Europe. For more than 40 years women in
      Germany have had legal and free access to a conventional cytologic smear test
      starting at the age of 20 years. The introduction of the Pap smear subsequently
      led to a reduction in the incidence and mortality of cervical cancer. However,
      the low sensitivity of the Pap smear and the evidence regarding human
      papillomavirus (HPV) in the context of cervical cancer have led to a critical
      view of the existing early detection of cervical cancer. In the meantime, new
      screening methods have been developed and different HPV tests, liquid-based
      cytology, and novel biomarkers have become available. Several randomized studies
      have investigated HPV testing as a primary cervical cancer screening test,
      generating a large body of evidence. It is expected that a combination of HPV
      testing and cytology will improve cervical cancer screening. In the near future,
      the early detection of cervical cancer in Germany will be restructured on the
      basis of the German National Cancer Plan as well as the new Cancer Screening and
      Registers Act (KFRG). The European guidelines for quality assurance in cervical
      cancer screening will be taken into account, and an organized, population-based,
      and quality-assured cervical cancer screening program will be implemented.

PMID- 24562704
TI  - [Colorectal cancer screening: evidence and implementation].
AB  - BACKGROUND: Colorectal cancer (CRC) is the second most common cancer among both
      men and women in Germany. Owing to its relatively slow growth, perspectives for
      effective early detection are much better than for other forms of cancer. AIM: To
      summarize the evidence on effectiveness and cost-effectiveness of CRC screening,
      and to provide an overview on the current state and perspectives for effective
      CRC screening. MATERIALS AND METHODS: Summary and critical review of evidence
      from randomized trials and observational epidemiological studies. RESULTS: A
      reduction in CRC mortality by offering annual fecal occult blood tests or once
      only flexible sigmoidoscopy has been demonstrated in randomized trials. Novel
      fecal immunochemical tests for hemoglobin in stool have been shown to be more
      sensitive than traditional fecal occult blood tests and could substantially
      improve noninvasive CRC screening. Epidemiological studies suggest that the
      majority of CRC cases and deaths could be prevented by colonoscopy and removal of
      colorectal adenomas. However, adherence to screening offered outside organized
      screening programs is low. The National Cancer Plan recommends an organized CRC
      screening program in Germany. The law on the early detection of cancer from April
      2013 has paved the way for its implementation. DISCUSSION: The great potential
      for CRC prevention by early detection has so far only been realized to a very
      limited extent in Germany. Introduction of an organized screening program and the
      offer of enhanced noninvasive screening tests could strongly enhance the
      utilization and effectiveness of CRC screening in Germany. The political frame
      has been set, and timely quality-assured implementation is required.

PMID- 24562705
TI  - [Risk-adapted surveillance: focus on familial breast and ovarian cancer].
AB  - Breast cancer surveillance programs for the general population are not adequate
      for the small number of women with hereditary breast and ovarian cancer syndrome.
      Breast cancer screening for women in Germany starts at the age of 50 years, but
      nearly half of all women with familial risk are already diagnosed with breast
      cancer at that time. Moreover, mammography alone is not suitable for an early
      diagnosis of breast cancer in young women from high-risk families. Their typical
      dense breast tissue causes a high rate of false-negative cases. Therefore,
      national and international prospective clinical trials were initiated to offer a
      multimodal breast cancer surveillance program including magnetic resonance
      tomography for the breast and semi-annual screening intervals to women with
      BRCA1/2 mutations and those from high-risk families who tested negative for
      BRCA1/2 mutations. This program will currently be evaluated by the 15 centers of
      the German Consortium for Hereditary Breast and Ovarian Cancer.

PMID- 24562706
TI  - [Current results on PSA-based prostate cancer detection].
AB  - Prostate cancer is the most common cancer and the third leading cause of cancer
      specific death in men in Western industrialized countries. Implementation of the
      prostate-specific antigen (PSA) blood test as an early detection tool has led to
      a significant reduction of prostate cancer mortality in the USA. Apart from an
      earlier detection of clinically relevant tumors, regular PSA testing increases
      the risk of over-detection and over-treatment of clinically indolent tumors. In
      our view, a reliable stratification of indolent tumors in active surveillance
      programs is the key in avoiding or reducing overtreatment of early diagnosed
      prostate cancers. Along with better risk stratification, the expansion of PSA
      screening should be discussed in order to reduce the still high numbers of
      palliative treatments, metastases, and prostate cancer-related deaths. 

PMID- 24562707
TI  - [Early detection of prostate cancer: harm verified, benefit not verifiable].
AB  - The results of randomized studies on the early detection of prostate cancer and
      those of a systematic Cochrane review are compiled and interpreted. Some
      fundamental and inherent weaknesses of screening studies are pointed out and
      discussed. The meta-analysis of studies involving a total of 321,594 participants
      shows no reduction in prostate cancer mortality or all-cause mortality, but
      describes disadvantages such as unnecessary biopsies, overdiagnosis, and
      overtreatment. A relevant increase in overall mortality cannot be excluded. Even
      in future trials, the possible reduction of prostate cancer mortality or all
      cause mortality by prostate cancer screening will not be detectable because of
      inherent methodological problems, e.g., an extremely high number of participants
      are needed. Furthermore, by nature, studies on the early detection of cancer last
      very long, such that the results are inevitably outdated at the end of the study.
      There is a risk that studies on the early detection of cancer suggest an
      advantage and at the same time overlook a relevant increase in overall mortality.
      Prostate cancer screening also ignores important WHO criteria for screening
      programs: There is evidence that early treatment of prostate cancer is not better
      than late treatment. There is no suitable or reliable test to identify the early
      stages of the disease. The benefit-risk ratio is not clearly favorable, and there
      is doubt whether the costs and the benefits are in an acceptable balance. There
      are valid reasons to advise against population-based prostate cancer screening. 

PMID- 24562708
TI  - [Cancer screening from the perspective of public health ethics].
AB  - Cancer screening programs aim at reducing the tumor-related morbidity and
      mortality by early detection of malignant tumors or precancerous lesions. The
      basic ethical dilemma in cancer screening is, however, that many people have to
      be exposed to the burdens and risks of the intervention for a few people to
      benefit from early cancer diagnosis. This article discusses under which
      conditions it is ethically acceptable to offer or even recommend cancer
      screening. First, the benefit of the program in terms of a reduced cancer-related
      mortality should be proven by randomized controlled trials. The risks and burdens
      of the program related to the side effects of the investigation itself, false
      positive findings, as well as overdiagnoses and overtherapy should be in an
      acceptable relationship to the expected benefit of the program. In addition to a
      solid empirical scientific basis, the benefit-harm evaluation necessarily
      involves value judgments. The potential participants in the screening program
      therefore should receive transparent, objective, unbiased, and understandable
      information to enable them to make a truly informed choice about participation.
      Given the complex benefit-risk assessment, it is discussed whether-and if so
      under which circumstances-it is ethically acceptable to make a recommendation for
      or against participation in a cancer screening program. Socioempirical research,
      such as focus group studies and public deliberations, can be used to elicit the
      preferences and value judgments of members of the target population that should
      be taken into consideration in recommendations about a cancer screening program.

PMID- 24562709
TI  - ["IGeL" or not: cancer screening always needs comprehensive information].
AB  - BACKGROUND: Cancer screening tests such as ultrasound scans, extensive skin
      cancer screening, or the prostate-specific antigen (PSA) test are among the most
      commonly used individual out-of-pocket health services (in German: Individuelle
      Gesundheitsleistungen, or IGeL) among people who have statutory health insurance
      in Germany. They are usually offered as an add-on to the services that are
      covered by statutory insurers. QUESTIONS AND METHODS: There are a number of
      reasons why cancer screening tests might not be covered by insurers. The main
      reasons are because the test does not have any clear benefits, and because the
      harms outweigh the benefits. This article describes the fundamental difficulties
      of, and the requirements imposed on, benefit assessments of cancer screening
      tests. RESULTS: Cancer screening tests that are available as individual out-of
      pocket health services are always potentially harmful, while their benefit is
      either not clear or contested, or there is clearly no benefit. DISCUSSION: Health
      care providers who offer cancer screening tests are required to provide
      interested people with relevant information on the related benefits, harms, and
      uncertainties of the tests, so as to enable an informed decision. This is
      especially important when it comes to "IGeL" services.

PMID- 24562710
TI  - [Prevention of skin cancer: considerations on strategic communication].
AB  - In recent decades the numbers of cases of skin cancer have been increasing
      worldwide in light skinned populations. In Germany skin cancer is the most common
      form of cancer. To reduce the burden of skin cancer protection from ultraviolet
      radiation (primary prevention) and early detection (secondary prevention) of the
      disease play a decisive role. In this context information to the population about
      preventive behavior and the support of informed decision-making in skin cancer
      screening are important aspects in communication. This paper gives an overview
      about communicational aspects in the promotion of skin cancer prevention. In the
      development of communicational interventions it is important to identify the
      relevant target groups. Relevant key opinion leaders have to be included in the
      information process. Additionally, interventions should be based on a theoretical
      framework and be designed for the respective target group. Furthermore, different
      forms of communication and communication tools are provided for the realization
      of an information intervention. To appraise the intervention elements of
      summative and formal evaluation are available. The current results provide
      important findings about different effects of communicational aspects on
      knowledge and behavior of the population; however, due to the complexity of
      information interventions a particular effect cannot be explained by a single
      communicational element.

PMID- 24562711
TI  - [Towards informed choice: design and results of projects on (cancer) screening
      funded by the Federal Ministry of Health].
AB  - There has been a gradual paradigm shift in the area of screening and early
      detection of diseases. For many years, the sole focus of public health policies
      was increasing the uptake rates in screening programs. However, today there is an
      increasing awareness of the importance of informed decision making --
      particularly in the area of screening. The provision of high-quality, evidence
      based, and comprehensive information on benefit and harm is an important approach
      in achieving this objective. The current paper presents a project that was funded
      by the Federal Ministry of Health. It examines whether existing information
      material is appropriate to support informed decision making. In the first phase
      of the project, different screening procedures were assessed systematically and
      compared using several indicators. Based on the results of an expert workshop,
      the subsequent research activities focused on colorectal cancer (CRC) screening
      as one example. Phase II included the systematic search and assessment of print
      media, e.g., flyers and brochures, while phase III applied the same methods to
      websites on CRC screening. The information material was analyzed with a mix of
      methods, involving both experts and users. Finally, the results were presented
      and discussed with the authors/providers of the information material. Based on
      the results of this project, the Federal Center for Health Education developed a
      module on CRC screening for an Internet platform on women's health that is
      currently being evaluated. In sum, this research project contributes to the
      development of evidence-based and balanced information as well as informed
      decision making. 

PMID- 24562712
TI  - [Leaflets and websites on colorectal cancer screening and their quality
      assessment from experts' views].
AB  - In Germany, individuals who have statutory health insurance have free access to
      colorectal cancer (CRC) screening tests, and can choose between a fecal occult
      blood test and a screening colonoscopy. Evidence-based health information may
      support informed choices regarding whether or not to undergo CRC screening. The
      aim of this study was to assess whether the available German information
      materials on CRC screening meet evidence-based health information standards. A
      systematic search was made for print media and websites on CRC screening
      addressed to German people with average CRC risk (search period for print media
      August 2010, for websites January-March 2012). The identified information was
      assessed with a newly developed comprehensive list of criteria. In all, 41 print
      media, including 28 flyers and 13 brochures, and 36 websites were identified and
      assessed. These materials reported more often the benefits than the risks of CRC
      screening, and quantified presentations of benefits and risks were less
      frequently given. Most of the materials called for participation and did not
      indicate the option to decide whether or not to attend CRC screening. This bias
      in favor of screening was increased by fear-provoking or downplayed wording. Most
      materials included false and misleading information. The requirements for
      evidence-based patient information were currently not met by most of the leaflets
      and websites in Germany. Feedback was given to the producers of the leaflets
      including a discussion of the findings. The results may be used to revise
      existing leaflets or to develop new health information on CRC screening. 

PMID- 24562714
TI  - [Information on early detection of colorectal cancer: development of an
      information module for the women's health portal of the Federal Center for Health
      Education (BZgA)].
AB  - Colorectal cancer is the second most prevalent cancer in Germany. The
      governmental program for early detection of colorectal cancer intends to increase
      the chances of recovery by identifying colorectal cancer in an early, more
      treatable stage. Citizens need quality-assured, balanced, and target-group
      specific information to be able to make an informed decision. On the basis of the
      current state of research, of extensive studies, and of expert and user
      interviews, the Federal Center for Health Education (BZgA) developed an
      information module on"early detection of colorectal cancer" for the women's
      health portal of the BZgA. The information module contains information on
      colorectal cancer, on the governmental program for early detection, as well as on
      the program's benefits and risks. The information offered is intended to be up to
      date and is approved by experts. The BZgA approves the quality of this
      information using methods of process and outcome evaluation. 

PMID- 24562713
TI  - [Are German information materials on colorectal cancer screening understandable
      or do they fail? Rating of health information by users with different educational
      backgrounds].
AB  - Evidence-based patient information is an essential part of decision making in
      health issues. A qualitative study was conducted to examine whether consumers
      consider the health information on colorectal cancer screening in Germany helpful
      in supporting their decision making. In this study, eight texts from different
      German authors about colorectal cancer screening were evaluated with a criteria
      based selection. The texts were tested for understandability, structure, design,
      and effect on readers. Thirteen semi-structured focus groups were formed
      including 59 higher-educated and 15 lower-educated testers, 46 % of them being
      male with a mean age of 62.9 years. The transcripts were analyzed by content
      analytic assessment. The testers provided detailed comments on the content and
      design of the texts. They revealed inaccuracies and suggested improvements of the
      texts. The testers differed from each other in terms of the intensity of their
      participation in the discussions and comprehension of the material. The reception
      of the flyers and brochures varied according to the educational level of the
      testers. Lower-educated testers often skipped passages of texts about risks as
      well as passages containing numbers and graphics. The texts had different effects
      on the testers, regardless of the level of education. If adverse effects were
      presented, some testers became scared while others were reassured because they
      felt informed. Most of the testers appreciated a call for participation as a
      central message of the text. Sometimes, if there was no clear appeal to attend
      the screening, the testers even asked for it. The recently introduced political
      strategy of promoting an informed choice is applied to an unprepared population
      who was used to getting a clear yes-or-no recommendation. Thus, at first, the
      population has to learn how to make an informed choice. This topic must be
      addressed and taken into account in the process of developing health information.
      Since this is not always the case, we conclude that current materials are limited
      in their contribution toward the decision of attending CRC screening.

PMID- 24562716
TI  - Role of oxygen vacancy and Fe-O-Fe bond angle in compositional, magnetic, and
      dielectric relaxation on Eu-substituted BiFeO(3) nanoparticles.
AB  - The influence of oxygen vacancies on the dielectric relaxation behavior of pure
      and Eu-substituted BiFeO3 nanoparticles synthesized by a sol-gel technique has
      been studied using impedance spectroscopy in the temperature range of 90  degrees
      C to 180  degrees C. The electric relaxation time and activation energy of the
      oxygen vacancies can be calculated from the Arrhenius equation, and found to be
      1.26 eV and 1.76 eV for pure and Eu-substituted BiFeO3, respectively.
      Substitution induces structural disorder and changes in the Fe-O-Fe bond angle,
      leading to alteration of the magnetic properties, observed from magnetic studies
      and evaluated using Rietveld refinement of the XRD patterns. X-ray photoelectron
      spectroscopy (XPS) confirms the shifting of the binding energy of the Bi 4f
      orbital, establishing Eu substitution at the Bi site. Calculation of the area
      under the Fe(2+)/Fe(3+) (2p) and O (1s) XPS spectra gives approximate values of
      the oxygen vacancies. 

PMID- 24562717
TI  - Identifying 22q11.2 deletion syndrome and psychosis using resting-state
      connectivity patterns.
AB  - The clinical picture associated with 22q11.2 deletion syndrome (22q11DS) includes
      mild mental retardation and an increased risk of schizophrenia. While the
      clinical phenotype has been related to structural brain network alterations,
      there is only scarce information about functional connectivity in 22q11DS.
      However, such studies could lead to a better comprehension of the disease and
      reveal potential biomarkers for psychosis. A connectivity decoding approach was
      used to discriminate between 42 patients with 22q11DS and 41 controls using
      resting-state connectivity. The same method was then applied within the 22q11DS
      group to identify brain connectivity patterns specifically related to the
      presence of psychotic symptoms. An accuracy of 84 % was achieved in
      differentiating patients with 22q11DS from controls. The discriminative
      connections were widespread, but predominantly located in the bilateral frontal
      and right temporal lobes, and were significantly correlated to IQ. An 88 %
      accuracy was obtained for identification of existing psychotic symptoms within
      the patients group. The regions containing most discriminative connections
      included the anterior cingulate cortex (ACC), the left superior temporal and the
      right inferior frontal gyri. Functional connectivity alterations in 22q11DS
      affect mostly frontal and right temporal lobes and are related to the syndrome's
      mild mental retardation. These results also provide evidence that resting-state
      connectivity can potentially become a biomarker for psychosis and that ACC plays
      an important role in the development of psychotic symptoms. 

PMID- 24562718
TI  - A rare cause for lower back pain: a case of an IgG4-related periaortitis.
AB  - IgG4-related disease (IgG4-RD) are a group of autoinflammatory diseases often
      presenting as tumor-like lesions because of their infiltrative or mass forming
      behavior. They are characterized by a typical histology consisting of storiform
      fibrosis, high numbers of infiltrating IgG4-positive plasma cells, obliterative
      phlebitis, and a moderate presence of eosinophilic cells. Serum IgG4 levels can
      be elevated. We present a case of a 57 year-old male patient with immobilizing
      lower back pain, fever, and night sweats. We diagnosed IgG4-related periaortitis
      using serum IgG4 levels, abdominal ultrasound, PET/CT, and histology. We
      successfully treated the patient with glucocorticoids (GC) and azathioprine.
      Periaortitis is a rare presentation of IgG4-RD and therefore noteworthy. It has
      to be considered in patients with a retroperitoneal mass.

PMID- 24562719
TI  - Interchangeability of 28-joint disease activity scores using the erythrocyte
      sedimentation rate or the C-reactive protein as inflammatory marker.
AB  - This paper aims to examine the interchangeability of the disease activity score
      in 28 joints (DAS28)-erythrocyte sedimentation rate (ESR) and DAS28-CRP scores in
      a diverse sample of rheumatoid arthritis (RA) patients and to evaluate
      generalizability over gender, age, and disease duration. A sample of 682 patients
      was drawn from the DREAM registry. Agreement between the two DAS28 scores was
      analyzed using the intraclass correlation coefficient (ICC), Bland Altman plots,
      and a matrix of classification agreement over DAS28 disease activity categories.
      Despite a strong linear correlation between the DAS28 scores and a high ICC value
      of 0.931, a considerable lack of individual agreement could be observed, with
      Bland-Altman 95% limits of agreement ranging between -0.85 and +1.25 points. On
      average, DAS28-CRP scores were 0.20 points lower than DAS28-ESR scores, and data
      stratification on age and gender showed that this systematic bias was most severe
      in older women (0.39 points). The overall classification agreement across DAS28
      categories was 76.69%, with the agreement being lowest (35.37%) in the low
      disease activity group. Patients were more easily classified as being in
      remission when using the DAS28-CRP measure. DAS28-ESR and DAS28-CRP scores are
      not interchangeable within individuals. The DAS28-CRP tends to yield lower values
      of disease activity than the DAS28-ESR, resulting in substantial classification
      differences.

PMID- 24562721
TI  - Acute anterior uveitis as the presenting feature of Kawasaki disease.

PMID- 24562722
TI  - Granulocytic sarcoma of bladder in an 18-mo-old child with acute myeloid
      leukemia.

PMID- 24562723
TI  - Perceived threat in childhood: a review of research and implications for children
      living in violent households.
AB  - The current study is a review of existing literature on perceived threat across
      childhood (0-19 years). There is strong evidence from this body of research that
      threat detection emerges in infancy and is present throughout childhood, with
      meaningful links to child adjustment. The wide range of methodologies employed to
      assess threat include biological measures (event-related potential and functional
      magnetic resonance imaging), observational data (gaze duration and response
      time), and a range of ways of gathering cognitive data (threat appraisal). Across
      methodologies, a uniform finding is that children who have higher threat
      attenuation are at increased risk for the development of anxiety disorders. It
      also seems that children's attention to threatening stimuli may vary across
      development, with heightened attention in infancy and early childhood. These
      findings have meaningful extensions for children who are living in violent
      families. Since many children living in violent homes are exposed to the threat
      of violence beginning in infancy, these children may be at heightened risk as
      compared to their nonexposed peers for the development of maladaptive patterns of
      threat detection and response. There is some evidence that this long-standing
      pattern of vigilance toward threat in key developmental periods may in part
      explain the increased risk of the development of anxiety disorders and
      posttraumatic stress disorder following exposure to violence. 

PMID- 24562724
TI  - Use and misuse of research in books on sex trafficking: implications for
      interdisciplinary researchers, practitioners, and advocates.
AB  - Recent articles have raised important questions about the validity of prevalence
      data on human trafficking, exposing flawed methodologies behind frequently cited
      statistics. While considerable evidence points to the fact that human trafficking
      does exist in the United States and abroad, many sources of literature continue
      to cite flawed data and some misuse research in ways that seemingly inflate the
      problem, which can have serious implications for anti-trafficking efforts,
      including victim services and anti-trafficking legislation and policy. This
      systematic review reports on the prevalence data used in 42 recently published
      books on sex trafficking to determine the extent to which published books rely on
      data estimates and just how they use or misuse existing data. The findings from
      this review reveal that the vast majority of published books do rely on existing
      data that were not rigorously produced and therefore may be misleading or at
      minimum, inaccurate. Implications for practice, research, and policy are
      discussed, as well as recommendations for future prevalence studies on human
      trafficking. 

PMID- 24562725
TI  - Thinking critically about campus-based self-defense programs: a response to
      Christine Gidycz.
AB  - Often labeled "ivory towers," colleges are fertile breeding grounds of male to
      female sexual assault and other types of woman abuse. Still, across the United
      States and elsewhere, many researchers, practitioners, and activists are involved
      in an ongoing and ever-changing struggle to curb female victimization in
      institutions of higher learning. The main objective of this article is to offer a
      few thoughts about some prevention issues raised by Christine Gidycz. Special
      attention is devoted to the dangers associated with new electronic technologies,
      including texting and Internet pornography. 

PMID- 24562726
TI  - Optimal flip angle of Gd-EOB-DTPA-enhanced MRI in patients with hepatocellular
      carcinoma and liver metastasis.
AB  - PURPOSE: To investigate optimal flip angle (FA) of three-dimensional fat
      suppressed T1-weighted image on Gd-EOB-DTPA-enhanced MRI. METHODS: Forty-five
      patients with 35 hepatocellular carcinomas (HCCs) and 16 liver metastases (METs)
      were investigated. Signal-to-noise ratio (SNR), tumor-to-liver contrast (TLC) of
      HCC and MET, visual image quality (IQ) and lesion conspicuity (LeCo) were
      evaluated at hepatobiliary phase with different FAs (FA15 degrees -30 degrees -45
      degrees -60 degrees  in 13 patients, FA5 degrees -10 degrees -15 degrees -20
      degrees -25 degrees  in 32 patients). RESULTS: TLC gradually showed better in
      range from FA15 degrees  to FA60 degrees  and FA5 degrees  to FA25 degrees , but
      SNRs gradually decreased. SNR and TLC-MET at FA15 degrees  were significantly
      better than those at FA45 degrees  and FA60 degrees . SNR at FA10 degrees  was
      significantly higher than at FA5 degrees , FA20 degrees , and FA25 degrees . TLC
      HCC and TLC-MET at FA5 degrees  were inferior to other FAs. IQs and LeCos at FA15
      degrees  and FA30 degrees  were superior to those at FA45 degrees  and FA60
      degrees . IQs at FA5 degrees  and FA25 degrees  were significantly lower than
      those at FA10 degrees -20 degrees , although LeCos for HCC and MET at FA25
      degrees  were superior to those at FA5 degrees -20 degrees . CONCLUSIONS: FA
      ranging from 10 degrees  to 20 degrees  is suitable for hepatobiliary phase of Gd
      EOB-DTPA-enhanced MRI, to image HCC and MET.

PMID- 24562745
TI  - Synthesis and structural studies of the simplest bismuth(III) oxo-salicylate
      complex: [Bi4(MU3-O)2(HO-2-C6H4CO2)8].2Solv (Solv = MeCN or MeNO2).
AB  - Reaction of BiPh3 with salicylic acid (HO-2-C6H4CO2H, H2Sal) at room temperature
      in wet acetonitrile or nitromethane leads to the facile formation of an oxo
      cluster compound with formula [Bi4(MU3-O)2(HSal)8] solvated by either MeCN and
      MeNO2 (1.2MeCN or 1.2MeNO2). This simple procedure affords a convenient, high
      yield (>80%) synthesis of a single bismuth oxo cluster. Both adducts exhibit a
      nearly planar Bi4(MU3-O)2 core. The solvent ligands are situated in the same
      coordination sites in both but at long Bi-N and Bi-O distances. The ease of
      preparation as a pure compound makes this an ideal starting material for study of
      bismuth oxo-salicylate chemistry. 

PMID- 24562737
TI  - Functional brain connectivity using fMRI in aging and Alzheimer's disease.
AB  - Normal aging and Alzheimer's disease (AD) cause profound changes in the brain's
      structure and function. AD in particular is accompanied by widespread cortical
      neuronal loss, and loss of connections between brain systems. This degeneration
      of neural pathways disrupts the functional coherence of brain activation. Recent
      innovations in brain imaging have detected characteristic disruptions in
      functional networks. Here we review studies examining changes in functional
      connectivity, measured through fMRI (functional magnetic resonance imaging),
      starting with healthy aging and then Alzheimer's disease. We cover studies that
      employ the three primary methods to analyze functional connectivity--seed-based,
      ICA (independent components analysis), and graph theory. At the end we include a
      brief discussion of other methodologies, such as EEG (electroencephalography),
      MEG (magnetoencephalography), and PET (positron emission tomography). We also
      describe multi-modal studies that combine rsfMRI (resting state fMRI) with PET
      imaging, as well as studies examining the effects of medications. Overall,
      connectivity and network integrity appear to decrease in healthy aging, but this
      decrease is accelerated in AD, with specific systems hit hardest, such as the
      default mode network (DMN). Functional connectivity is a relatively new topic of
      research, but it holds great promise in revealing how brain network dynamics
      change across the lifespan and in disease.

PMID- 24562744
TI  - Experimental evaluation of ultrasound-guided 3D needle steering in biological
      tissue.
AB  - PURPOSE: In this paper, we present a system capable of automatically steering
      bevel tip flexible needles under ultrasound guidance toward stationary and moving
      targets in gelatin phantoms and biological tissue while avoiding stationary and
      moving obstacles. We use three-dimensional (3D) ultrasound to track the needle
      tip during the procedure. METHODS: Our system uses a fast sampling-based path
      planner to compute and periodically update a feasible path to the target that
      avoids obstacles. We then use a novel control algorithm to steer the needle along
      the path in a manner that reduces the number of needle rotations, thus reducing
      tissue damage. We present experimental results for needle insertion procedures
      for both stationary and moving targets and obstacles for up to 90 mm of needle
      insertion. RESULTS: We obtained a mean targeting error of [Formula: see text] and
      [Formula: see text] mm in gelatin-based phantom and biological tissue,
      respectively. CONCLUSIONS: The achieved submillimeter accuracy suggests that our
      approach is sufficient to target the smallest lesions ([Formula: see text] 2 mm)
      that can be detected using state-of-the-art ultrasound imaging systems.

PMID- 24562746
TI  - Photo quiz: a 47-year-old female with general fatigue, fever, and respiratory
      symptoms. Answer to photo quiz: bacteremia caused by Tsukamurella
      tyrosinosolvens.

PMID- 24562747
TI  - Absence of pleocytosis alone is insufficient to exclude encephalitis caused by
      herpes simplex virus in children.

PMID- 24562748
TI  - Reply to "Absence of pleocytosis alone is insufficient to exclude encephalitis
      caused by herpes simplex virus in children".

PMID- 24562753
TI  - A metal-organic framework assembled from Y(III), Li(I), and terephthalate:
      hydrothermal synthesis, crystal structure, thermal decomposition and topological
      studies.
AB  - A novel metal-organic framework assembled from Y(iii), Li(i), and terephthalate
      ligand, formulated as [LiY(BDC)2(H2O).2(H2O)] (1) (H2BDC = terephthalic acid),
      has been obtained as single phase under hydrothermal conditions. The crystal
      structure was solved by single-crystal X-ray diffraction and the bulk was
      characterized by powder X-ray diffraction (PXRD), thermal analyses (TG-MS and
      DSC), vibrational spectroscopy (FTIR), scanning/transmission electron microscopy
      (SEM-EDX, TEM, SAED, and BF-STEM-EDX), and powder X-ray thermodiffractometry (HT
      XRD). 1 crystallizes in monoclinic space group (P21/c, with a = 11.6415(7) A, b =
      16.0920(4) A, c = 13.2243(8) A and beta = 132.23(1) degrees ) and possesses a 3D
      framework with 1D trigonal channels running along the [101] direction containing
      water molecules. The structure of 1 is made up of unusual four-membered rings
      formed by edge- and vertex-shared {YO8} and {LiO4} polyhedra. The four-membered
      rings are isolated and connected to each other via carboxylate groups. HT-XRD
      reveals that 1 undergoes phase transformation upon the dehydration process which
      is a reversible process involving a spontaneous rehydration characterized by fast
      kinetics. Topological studies were also performed revealing that 1 has a new 2
      nodal net. 

PMID- 24562754
TI  - Outcomes after endocarditis or device infection in patients with left ventricular
      epicardial leads versus coronary sinus leads.
AB  - BACKGROUND: There is scant data about outcomes in patients with left ventricular
      epicardial (LVE) leads who develop endocarditis or device-related infection.
      OBJECTIVE: This retrospective study evaluated mortality and recurrence of
      infection among patients with LVE leads in comparison to patients with
      endovascular coronary sinus (CS) leads after the development of endocarditis or
      device-related infection. METHODS: Patients with cardiac resynchronization
      therapy (CRT) devices who developed endocarditis or pocket infection over 5 years
      at Cleveland Clinic were included in the study. The groups were all patients with
      LVE leads versus CRT devices without epicardial leads that developed endocarditis
      or pocket infection. Mortality was assessed using the Social Security Death Index
      and re-infection was assessed by reviews of the medical record. RESULTS:
      Prospective extraction of the CRT device and leads occurred among all 50 patients
      with CS leads and 8 of the 14 patients with LVE leads. The survival rate was 92.9
      versus 92 % and freedom from re-infection rate was 64.3 versus 80 % in the
      patients with LVE leads versus CS leads, respectively, over 1 year (P value =
      0.918 and 0.226, respectively). At 3 years, the survival rate in LVE lead group
      was 92.9 % and freedom from re-infection rate was 64.3 % in comparison to
      survival rate of 90 % and freedom from re-infection rate of 68 % in the CS group
      (P value = 0.751 and 0.798, respectively). CONCLUSION: After development of
      endocarditis or pocket infection, no statistically significant differences were
      seen in mortality, or recurrent infection between patients with LVE leads and
      those with CS leads.

PMID- 24562755
TI  - [Not Available].
AB  - From the different methods for risk adjustment, scores allow a rough
      classification of the patients. The Euroscore represents one of the most modern
      scores. The most recent version of the documentation system of the German Society
      for Thoracic and Cardiovascular Surgery may be used without extended extra-work
      to evaluate the Euroscore despite the presence of various limitations. The
      investigation of the scores with nearly complete adaptation of the variables of
      the quality assurance documentation to the original definition showed no
      substantial differences between the score groups. However, many methodological
      implications favor the development of self-evaluated models to obtain a most
      recent weight for each risk factor and to be able to take into account new
      therapeutical options. These models can be evaluated by the existing database and
      extended by the most recent data. 

PMID- 24562756
TI  - [Not Available].
AB  - Objective Among other adjunctive medication, heparin is widely used in the
      therapy of acute myocardial infarction (AMI) today. Large randomized trials,
      however, have shown inconclusive data on the benefit of adjunctive heparin
      therapy for patients with AMI. The aim of this study was to describe the use of
      heparin and complication rates in routine clinical practice today. Methods MITRA
      and MIR were multicenter registries of AMI patients in Germany. During the years
      1994 to 1998, 22697 patients were registered with MITRA and MIR. Of these
      patients 49.9% received reperfusion therapy. Results 21004 patients (92%)
      received heparin during acute therapy of AMI. The following factors were
      associated with withholding heparin: Bleeding at admission (OR 4.7; CI 3.2-6.8),
      cardiogenic shock (OR 1.8; CI 1.4-2.3) and fibrinolytic therapy with
      streptokinase (OR 2.1; CI 1.8-2.3). Complication rates of patients with heparin
      were only slightly higher than among those without heparin: 1.7% strokes and 1.9%
      bleedings were reported among the patients with fibrinolysis and heparin compared
      to 1.3% strokes and 1.4% bleedings among patients without heparin (p=ns).
      Mortality rates were 14.1% for patients with and 27.3% for patients without
      heparin (p<0.001). Conclusions Of the patients in MITRA and MIR 92% received
      heparin during AMI. Patients with active bleeding or in critical condition
      received heparin significantly less often. The selection of critically ill
      patients may have contributed to the high mortality of patients without heparin
      for AMI. Bleeding complication rates of patients with adjunctive heparin were
      only sightly higher than reported in randomized trials. 

PMID- 24562757
TI  - [Not Available].
AB  - Acute left main coronary artery (LMCA) occlusion is associated with a high
      mortality rate. The majority of patients with this clinical condition die
      suddenly or from cardiogenic shock. We report a case of cardiogenic shock
      resulting from acute main coronary occlusion. Emergency cardiac catheterization
      was performed and coronary angiography showed a totally occluded LMCA. Prompt
      revascularization by means of primary LMCA stenting was successful and the
      patient was discharged 16 days later without neurological deficit or clinical
      signs of heart failure. We suggest that the rapid coronary angiography followed
      by angioplasty and primary stent implantation was instrumental in saving this
      patient's life. 

PMID- 24562758
TI  - Glutathione deficiency leads to riboflavin oversynthesis in the yeast Pichia
      guilliermondii.
AB  - The Pichia guilliermondii GSH1 and GSH2 genes encoding Saccharomyces cerevisiae
      homologues of glutathione (GSH) biosynthesis enzymes, gamma-glutamylcysteine
      synthetase and glutathione synthetase, respectively, were cloned and deleted.
      Constructed P. guilliermondii Deltagsh1 and Deltagsh2 mutants were GSH
      auxotrophs, displayed significantly decreased cellular GSH+GSSG levels and
      sensitivity to tert-butyl hydroperoxide, hydrogen peroxide, and cadmium ions. In
      GSH-deficient synthetic medium, growths of Deltagsh1 and Deltagsh2 mutants were
      limited to 3-4 and 5-6 cell divisions, respectively. Under these conditions
      Deltagsh1 and Deltagsh2 mutants possessed 365 and 148 times elevated riboflavin
      production, 10.7 and 2.3 times increased cellular iron content, as well as 6.8
      and 1.4 fold increased ferrireductase activity, respectively, compared to the
      wild-type strain. Glutathione addition to the growth medium completely restored
      the growth of both mutants and decreased riboflavin production, cellular iron
      content, and ferrireductase activity to the level of the parental strain.
      Cysteine also partially restored the growth of the Deltagsh2 mutants, while
      methionine or dithiothreitol could not restore the growth neither of the
      Deltagsh1, nor of the Deltagsh2 mutants. Besides, it was shown that in GSH
      presence riboflavin production by both Deltagsh1 and Deltagsh2 mutants, similarly
      to that of the wild-type strain, depended on iron concentration in the growth
      medium. Furthermore, in GSH-deficient synthetic medium P. guilliermondii
      Deltagsh2 mutant cells, despite iron overload, behaved like iron-deprived wild
      type cells. Thus, in P. guilliermondii yeast, glutathione is required for proper
      regulation of both riboflavin and iron metabolism.

PMID- 24562759
TI  - Pseudomonas hunanensis sp. nov., isolated from soil subjected to long-term
      manganese pollution.
AB  - A Gram-negative, polar flagella, rod-shaped bacterium LV (T) was isolated from a
      soil sample subjected to long-term manganese pollution in Hunan Province, China.
      Cells grow optimally on Luria-Bertani agar medium at 30  degrees C in the
      presence of 0-5.0 % (w/v) NaCl and pH 7-8. 16S rRNA gene sequence analysis
      revealed that strain LV (T) belonged to the genus Pseudomonas, with sequence
      similarity values of 98.6, 98.2, 98.7, and 97.3 % to Pseudomonas monteilii BCRC
      17520 (T) , Pseudomonas putida BCRC 10459 (T) , Pseudomonas plecoglossicida BCRC
      17517 (T) , and Pseudomonas asplenii BCRC 17131 (T) , respectively. The level of
      DNA-DNA relatedness between the five strains was <30 %. The DNA G+C content of
      strain LV (T) is 68.8 mol%. Chemotaxonomic data revealed that the strain LV(T)
      possesses ubiquinone Q-9. The polar lipid profile of strain LV (T) contained
      diphosphatidylglycerol, phosphatidylglycerol, phosphatidylcholine, and
      phosphatidylethanolamine. The major cellular fatty acids present are C10:03-OH
      (12.33 %), C16:0 (23.99 %), summed feature 3(C16:1omega7c and/or C16:1omega6c),
      and summed feature 8(C18:1 omega7c and C18:1 omega6c). Based on the genotypic,
      chemotaxonomic and phenotypic data, strain LV (T) is distinguishable from related
      members of the genus Pseudomonas. Thus, strain LV (T) represents a novel species
      of the genus Pseudomonas, for which the name Pseudomonas hunanensis sp. nov. is
      proposed. The type strain is LV (T) (=CICC 10558(T) = NCCB 100446(T)).

PMID- 24562762
TI  - [Travel medicine].

PMID- 24562761
TI  - Impact of different ChIP-Seq protocols on DNA integrity and quality of
      bioinformatics analysis results.
AB  - Different ChIP-Seq protocols may have a significant impact on the final outcome
      in terms of quality, number and distribution of called peaks. Sample DNA
      undergoes a long procedure before the final sequencing step, and damaged DNA can
      result in excessive mismatches in the alignment with reference genome. In this
      letter, we present the effect of well-defined modifications (timing of
      formaldehyde crosslink reversal, brand of the sonicator) of standard ChIP-Seq
      protocol on parallel samples derived from the same cell line correlating the
      initial DNA quality control metrics to the final bioinformatics analysis results.

PMID- 24562760
TI  - Measuring resistant-genotype transmission of malaria parasites: challenges and
      prospects.
AB  - Increased gametocytemia in infections with resistant strains of Plasmodium
      species and their enhanced transmissibility are a matter of concern in planning
      and evaluating the impact of malaria control strategies. Various studies have
      determined weekly gametocyte carriage in response to antimalarial drugs in
      clinical trials. The advent of molecular biology techniques makes it easy to
      detect and quantify gametocytes, the stages responsible for transmission, and to
      detect resistant genotypes of the parasite. With the validation of molecular
      markers of resistance to certain antimalarial drugs, there is a need to devise a
      simpler formula that could be used with these epidemiological antimalarial
      resistance tools. Theoretical models for transmission of resistant malaria
      parasites are difficult to deploy in epidemiological studies. Therefore, devising
      a simple formula that determines the potential resistant-genotype transmission of
      malaria parasites should provide further insights into understanding the spread
      of drug resistance. The present perspective discusses gametocytogenesis in the
      context of antimalarial treatment and drug resistance. It also highlights the
      difficulties in applying the available theoretical models of drug resistance
      transmission and suggests Rashad's devised formula that could perhaps be used in
      determining potentially transmissible resistant genotypes as well as in mapping
      areas with high potential risk for the transmission of drug-resistant malaria.
      The suggested formula makes use of the data on gametocytes and resistant
      genotypes of malaria parasites, detected by molecular techniques in a certain
      geographical area within a particular point in time, to calculate the potential
      risk of resistant genotype transmission. 

PMID- 24562763
TI  - [Traveling with immunosuppression].
AB  - The rapidly increasing number of patients with immunosuppression is followed by
      their expectation to lead-as much as possible-a "normal" life, including long
      distance travel. The advice and preventive measures for diseases associated with
      travelling depend overall on the mode of the patient's immunosuppression. This
      report explains the individual preventive possibilities, limits and risks for
      travellers with asplenia, common variable immunodeficiency, chronic inflammatory
      bowel and rheumatic diseases, HIV, as well as for patients having undergone solid
      organ or bone marrow transplantation or chemotherapy. 

PMID- 24562764
TI  - Evaluating efficacy of field-generated electrochemical oxidants on disinfection
      of fomites using bacteriophage MS2 and mouse norovirus MNV-1 as pathogenic virus
      surrogates.
AB  - Surface disinfection, as part of environmental hygiene practices, is an efficient
      barrier to gastroenteritis transmission. However, surface disinfectants may be
      difficult to obtain in remote, resource-limited, or disaster relief settings.
      Electrochemical oxidants (ECO) are chlorine-based disinfectants that can be
      generated using battery power to electrolyze brine (NaCl) solutions. Electrolysis
      generates a mixed-oxidant solution that contains both chlorine (HOCl, OCl(-)) and
      reactive oxygen species (e.g., .OH, O3, H2O2, and .O2-) capable of inactivating
      pathogens. One onsite generator of ECO is the Smart Electrochlorinator 200 (SE
      200, Cascade Designs, Inc.). In a laboratory study, we assessed ECO surface
      disinfection efficacy for two gastrointestinal virus surrogates: bacteriophage
      MS2 and murine norovirus MNV-1. We quantified both infectivity and nucleic acid
      inactivation using culture-dependent and independent assays. At free available
      chlorine concentrations of 2,500 ppm and a contact time of 30 s, ECO inactivation
      of infective MS2 bacteriophage exceeded 7 log10 compared to MNV-1 disinfection of
      approximately 2 log10. Genomic RNA inactivation was less than infective virus
      inactivation: MS2 RNA inactivation was approximately 5 log10 compared to MNV-1
      RNA inactivation of approximately 1.5 log10. The results are similar to
      inactivation efficacy of household bleach when used at similar free available
      chlorine concentrations. Our work demonstrates the potential of ECO solutions,
      generated onsite, to be used for surface disinfection. 

PMID- 24562765
TI  - Recent research related to juvenile sex offending: findings and directions for
      further research.
AB  - Serious scholarly inquiry into juvenile sex offending represents a relatively new
      field, dating from the mid 1940s. During the next 4 decades, a mere handful of
      articles exploring aspects of juvenile sex offending were added to the available
      literature. By the 1980s, however, the literature began to increase rapidly, a
      trend that continues today. The purpose of this article is a focused review of
      the juvenile sex offender literature cited in PubMed over the last 5 years (2009
      2013). The authors have chosen studies that will bring readers up to date on
      research they believe impacts our current understanding of best practices in the
      management of juvenile sex offending. For convenience, our review is organized
      into topical categories including research into characteristics and typologies of
      juvenile sex offenders, risk assessment and recidivism, assessment and treatment,
      the ongoing debate about mandatory registration of sex offenders as it applies to
      juveniles, and other thought provoking studies that do not fit neatly into the
      aforementioned categories. The studies included contain findings that both
      reinforce and challenge currently held notions about best practices concerning
      treatment and public policy, suggesting that our knowledge of the field continues
      to evolve in important ways.

PMID- 24562766
TI  - Nitro-oleic acid and epoxy-oleic acid are not altered in obesity and type 2
      diabetes.

PMID- 24562767
TI  - Nitro-oleic acid and epoxyoleic acid are not altered in obesity and type 2
      diabetes: reply.

PMID- 24562768
TI  - Regulatory RNAs and paracrine networks in the heart.
AB  - Cardiac hypertrophy and fibrosis are two closely related adaptive response
      mechanisms of the myocardium to mechanical, metabolic, and genetic stress that
      finally contribute to the development of heart failure (HF). This relation is
      based on a dynamic interplay between many cell types including cardiomyocytes and
      fibroblasts during disease progression. Both cell types secrete a variety of
      growth factors, cytokines, and hormones that influence hypertrophic cardiomyocyte
      growth and fibrotic fibroblast activation in a paracrine and autocrine manner. It
      has become evident that, aside proteinous signals, microRNAs (miRNAs) and
      possible other RNA species such as long non-coding RNAs are potential players in
      such a cell-to-cell communication. By directly acting as paracrine signals or by
      modulating downstream intercellular signalling mediators, miRNAs can act as
      moderators of the intercellular crosstalk. These small regulators can potentially
      be secreted in a 'mircrine' fashion, so that miRNAs can be assumed as the message
      itself. This review will summarize the recent findings about the paracrine
      crosstalk between cardiac fibroblasts and cardiomyocytes and addresses how miRNAs
      may be involved in this interplay. It also highlights therapeutic strategies
      targeting factors of pathological communication for the treatment of HF. 

PMID- 24562769
TI  - miR126-5p repression of ALCAM and SetD5 in endothelial cells regulates leucocyte
      adhesion and transmigration.
AB  - AIMS: miR126-5p is processed from the miR126-3p/-5p duplex, which is expressed in
      endothelial cells and gives rise to the guide strand miR126-3p and the passenger
      strand miR126-5p. miR126-3p has prominent roles in vascular development and
      diseases, whereas the expression and physiological functions of miR126-5p are
      unknown. The purpose of this study was to evaluate the expression and role of
      miR126-5p in blood vessel endothelial cells. METHODS AND RESULTS: miR126-5p is
      mostly expressed in blood vessel endothelial cells in vivo and in vitro. Gain-
      and loss-of-function approaches revealed that miR126-5p promotes leucocyte
      adhesion and represses leucocyte transendothelial migration. Two distinct target
      genes of miR126-5p in endothelial cells were identified: the activated leucocyte
      cell adhesion molecule (ALCAM) gene which codes for an adhesion molecule involved
      in leucocyte transendothelial migration and SetD5, a gene with previously unknown
      functions. Using either a blocking antibody or target protectors which
      specifically disrupt the miRNA/mRNA target pairing, we showed that miR126-5p
      promotes leucocyte adhesion by controlling the expression of SetD5 and represses
      transendothelial migration via the regulation of ALCAM. miR126-5p controls ALCAM
      and SetD5 expression in vivo in separate tissues and regulates leucocyte
      infiltration into inflamed lungs by repressing ALCAM expression. CONCLUSION:
      miR126-5p is a functional, endothelial-enriched microRNA that participates in the
      control of leucocyte trafficking by regulating the expression of ALCAM and SetD5.

PMID- 24562770
TI  - mTORC1/C2 and pan-HDAC inhibitors synergistically impair breast cancer growth by
      convergent AKT and polysome inhibiting mechanisms.
AB  - Resistance of breast cancers to targeted hormone receptor (HR) or human epidermal
      growth factor receptor 2 (HER2) inhibitors often occurs through dysregulation of
      the phosphoinositide 3-kinase, protein kinase B/AKT/mammalian target of rapamycin
      (PI3K/AKT/mTOR) pathway. Presently, no targeted therapies exist for breast
      cancers lacking HR and HER2 overexpression, many of which also exhibit
      PI3K/AKT/mTOR hyper-activation. Resistance of breast cancers to current
      therapeutics also results, in part, from aberrant epigenetic modifications
      including protein acetylation regulated by histone deacetylases (HDACs). We show
      that the investigational drug MLN0128, which inhibits both complexes of mTOR
      (mTORC1 and mTORC2), and the hydroxamic acid pan-HDAC inhibitor TSA
      synergistically inhibit the viability of a phenotypically diverse panel of five
      breast cancer cell lines (HR-/+, HER2-/+). The combination of MLN0128 and TSA
      induces apoptosis in most breast cancer cell lines tested, but not in the non
      malignant MCF-10A mammary epithelial cells. In parallel, the MLN0128/TSA
      combination reduces phosphorylation of AKT at S473 more than single agents alone
      and more so in the 5 malignant breast cancer cell lines than in the non-malignant
      mammary epithelial cells. Examining polysome profiles from one of the most
      sensitive breast cancer cell lines (SKBR3), we demonstrate that this MLN0128/TSA
      treatment combination synergistically impairs polysome assembly in conjunction
      with enhanced inhibition of 4eBP1 phosphorylation at S65. Taken together, these
      data indicate that the synergistic growth inhibiting consequence of combining a
      mTORC1/C2 inhibitor like MLN0128 with a pan-HDAC inhibitor like TSA results from
      their mechanistic convergence onto the PI3K/AKT/mTOR pathway, profoundly
      inhibiting both AKT S473 and 4eBP1 S65 phosphorylation, reducing polysome
      formation and cancer cell viability.

PMID- 24562772
TI  - Evaluation of the RHINO gene for breast cancer predisposition in Finnish breast
      cancer families.
AB  - Hereditary predisposition to breast cancer is largely affected by the mutations
      in the genes of the DNA repair pathways. Novel genes involved in DNA repair are
      therefore prospective candidates also for breast cancer susceptibility genes. The
      RHINO (Rad9, Rad1, Hus1-interacting nuclear orphan) gene plays a central role in
      DNA damage response and in cell cycle regulation. RHINO interacts with Rad9-Rad1
      Hus1 (9-1-1) complex and with ATR activator TopBP1, which recruit it to the site
      of DNA damage. We analyzed the effects of the germline variation in RHINO on
      breast cancer risk. We sequenced the coding region of the RHINO gene 466 index
      cases of Finnish breast cancer families and in 507 population controls. The
      genotypes of the most likely functional variant were further determined in a
      large dataset of 2,944 cases and 1,976 controls. We analyzed the common variation
      of the RHINO locus and determined the haplotypes using five SNPs in 1,531 cases
      and 1,233 controls. We identified seven variants including four missense
      variations, a 5' UTR variant, a silent variant, and a nonsense variant c.250C>T,
      R84X (rs140887418). All variants were also present in control individuals with
      frequencies close to those of the cases (P > 0.05). The c.250C>T variant was
      present in 12 breast cancer patients (0.4 %) and of 16 controls (0.8 %) with the
      difference not statistically significant (OR = 0.50, 95 %CI: 0.24-1.06, P =
      0.066). The haplotype frequencies did not differ in cases and controls (P =
      0.59). Germline variation in the RHINO gene is unlikely to influence inherited
      susceptibility to breast cancer.

PMID- 24562771
TI  - Dermcidin expression is associated with disease progression and survival among
      breast cancer patients.
AB  - Improved diagnostic screening has led to earlier detection of many tumors, but
      screening may still miss many aggressive tumor types. Proteomic and genomic
      profiling studies of breast cancer samples have identified tumor markers that may
      help improve screening for more aggressive, rapidly growing breast cancers. To
      identify potential blood-based biomarkers for the early detection of breast
      cancer, we assayed serum samples via matrix-assisted laser desorption ionization
      time of flight mass spectrometry from a rat model of mammary carcinogenesis. We
      found elevated levels of a fragment of the protein dermcidin (DCD) to be
      associated with early progression of N-methylnitrosourea-induced breast cancer,
      demonstrating significance at weeks 4 (p = 0.045) and 5 (p = 0.004), a time
      period during which mammary pathologies rapidly progress from ductal hyperplasia
      to adenocarcinoma. The highest serum concentrations were observed in rats bearing
      palpable mammary carcinomas. Increased DCD was also detected with immunoblotting
      methods in 102 serum samples taken from women just prior to breast cancer
      diagnosis. To validate these findings in a larger population, we applied a 32
      gene in vitro DCD response signature to a dataset of 295 breast tumors and
      assessed correlation with intrinsic breast cancer subtypes and overall survival.
      The DCD-derived gene signature was significantly associated with subtype (p <
      0.001) and poorer overall survival [HR (95 % CI) = 1.60 (1.01-2.51), p = 0.044].
      In conclusion, these results present novel evidence that DCD levels may increase
      in early carcinogenesis, particularly among more aggressive forms of breast
      cancer.

PMID- 24562785
TI  - Pediatric solid organ transplantation and osteoporosis: a descriptive study on
      bone histomorphometric findings.
AB  - BACKGROUND: Organ transplantation may lead to secondary osteoporosis in children.
      This study characterized bone histomorphometric findings in pediatric solid organ
      transplant recipients who were assessed for suspected secondary osteoporosis.
      METHODS: Iliac crest biopsies were obtained from 19 children (7.6-18.8 years, 11
      male) who had undergone kidney (n = 6), liver (n = 9), or heart (n = 4)
      transplantation a median 4.6 years (range 0.6-16.3 years) earlier. All patients
      had received oral glucocorticoids at the time of the biopsy. RESULTS: Of the 19
      patients, 21 % had sustained peripheral fractures and 58 % vertebral compression
      fractures. Nine children (47 %) had a lumbar spine BMD Z-score below -2.0.
      Histomorphometric analyses showed low trabecular bone volume (< -1.0 SD) in 6
      children (32 %) and decreased trabecular thickness in 14 children (74 %). Seven
      children (37 %) had high bone turnover at biopsy, and low turnover was found in 6
      children (32 %), 1 of whom had adynamic bone disease. CONCLUSIONS: There was a
      great heterogeneity in the histological findings in different transplant groups,
      and the results were unpredictable using non-invasive methods. The observed
      changes in bone quality (i.e. abnormal turnover rate, thin trabeculae) rather
      than the actual loss of trabecular bone, might explain the increased fracture
      risk in pediatric solid organ transplant recipients.

PMID- 24562786
TI  - Evidence for vital role of endo-beta-N-acetylglucosaminidase in the resistance of
      Arthrobacter protophormiae RKJ100 towards elevated concentrations of o
      nitrobenzoate.
AB  - Arthrobacter protophormiae RKJ100 was previously characterized for its ability to
      tolerate extremely high concentrations of o-nitrobenzoate (ONB), a toxic
      xenobiotic environmental pollutant. The physiological responses of strain RKJ100
      to >=30 mM ONB indicated towards a resistance mechanism manifested via alteration
      of cell morphology and cell wall structure. In this study, we aim to characterize
      gene(s) involved in the resistance of strain RKJ100 towards extreme
      concentrations (i.e. 150 mM) of ONB. Transposon mutagenesis was carried out to
      generate a mutant library of strain RKJ100, which was then screened for ONB
      sensitive mutants. A sensitive mutant was defined and selected as one that could
      not tolerate >=30 mM ONB. Molecular and biochemical characterization of this
      mutant showed that the disruption of endo-beta-N-acetylglucosaminidase (ENGase)
      gene caused the sensitivity. ENGase is an important enzyme for oligosaccharide
      processing and cell wall recycling in bacteria, fungi, plants and animals.
      Previous reports have already indicated several possible roles of this enzyme in
      cellular homeostasis. Results presented here provide the first evidence for its
      involvement in bacterial resistance towards extreme concentrations of a toxic
      xenobiotic compound and also suggest that strain RKJ100 employs ENGase as an
      important component in osmotic shock response for resisting extreme
      concentrations of ONB.

PMID- 24562788
TI  - Prevalence of unreported bowel symptoms in women with pelvic floor dysfunction
      and the impact on their quality of life.
AB  - INTRODUCTION AND HYPOTHESIS: Little information is available on the recurrent
      coexistence of pelvic organ prolapse (POP), urinary (UI) and/or anal (AI)
      incontinence and defecatory dysfunctions and the relationship between these
      disorders. The purpose of this study is to report the prevalence, bother, and
      impact on quality of life (QoL) of unreported bowel symptoms in women presenting
      to a Brazilian tertiary urogynecology clinic. METHODS: The study was a cross
      section survey of 172 patients with symptoms of pelvic floor disorders (PFD).
      Patients who reported any defecatory and/or continence disorders were included in
      the study group, and the others were included in the control group. Patients with
      UI were also compared with those with double incontinence (DI): AI and UI.
      Univariate analysis was conducted using the Mann-Whitney U test for continuous
      nonparametric data. RESULTS: After the interview, 54.6 % (n = 94) of patients
      presented AI and/or defecatory disorders: 67.0 % constipation, 41.4 % AI, and
      34.0 % fecal urgency. Women from the study group scored worse in the QoL
      questionnaires compared with women from the control group. Among women with UI,
      23.21 % had associated AI. Women with DI scored worse in the QoL questionnaires.
      CONCLUSION: Anal and urinary dysfunctions are usually associated and have a great
      impact on a woman's QoL. An integrated approach across specialties should lead to
      improved patient care. Therefore, our study is relevant because it emphasizes the
      importance of urogynecologists routinely investigating such symptoms. To do so,
      standardized questionnaires should be included in the evaluation of all these
      patients.

PMID- 24562789
TI  - The minimum important difference for the Pelvic Organ Prolapse-Urinary
      Incontinence Sexual Function Questionnaire.
AB  - INTRODUCTION AND HYPOTHESIS: Although the Pelvic Organ Prolapse-Urinary
      Incontinence Sexual Function Questionnaire (PISQ) is widely used to assess sexual
      function in women, the minimum important difference (MID) (defined as the
      smallest difference in scores of a patient-reported outcome measure that is
      perceived by patients as beneficial or harmful and which would lead the clinician
      to consider a change in treatment) is not known. The objective was to estimate
      the MID for the PISQ. METHODS: Two study populations, one of women with
      overactive bladder (OAB) and urgency UI (UUI) treated with tolterodine in a
      placebo-controlled trial (cohort I), and one of women treated surgically for
      prolapse and/or UI (cohort II) were used. Cohort I anchors were the Overactive
      Bladder Questionnaire (OAB-q), the Patient Perception of Bladder Condition
      (PPBC), the Patient Perception of Treatment Benefit Questionnaire (PPTBQ), and
      the change in number of UUI episodes in bladder diaries. Distribution MIDs were
      also calculated. RESULTS: In the anchor-based analysis, the MID values for
      changes in PISQ total scores at 3 months in cohort I were 5 points using the UUI
      anchor (diary-dry women), 5 points using the PPBC anchor, 5 points with the
      PPTBQ, and 9 points with the OAB-q. In cohort II, the MID at week 12 in PISQ
      total scores was 7 points in women with improved IIQ-7 scores. The distribution
      based MID in PISQ total scores was 5.3 points in cohort I and 5.8 points in
      cohort II. CONCLUSION: A reasonable estimate of MID for the PISQ total score is 6
      points. Improvements that meet these thresholds may be considered clinically
      important.

PMID- 24562787
TI  - Molecular biology of fuselloviruses and their satellites.
AB  - Fuselloviruses, also known as Sulfolobus Spindle-shaped viruses (SSVs), are
      "lemon"- or "spindle"-shaped double-stranded DNA viruses. Among them, SSV1, SSV2
      and the satellite viruses pSSVx and pSSVi have been investigated at the
      structural, genetic, transcriptomic, proteomic and biochemical levels, thus
      becoming models for dissecting DNA replication/gene expression in Archaea.
      Important progress has been made including elucidation of temporal genome
      expression during virus infection and induction of replication, SSV1 lysogeny
      maintenance as well as differentially expression of pSSVx replicase. Future
      researches focusing on these model systems would yield insightful knowledge of
      life cycle and DNA replication of fuselloviruses. 

PMID- 24562792
TI  - An efficient wavelet analysis method to film-pore diffusion model arising in
      mathematical chemistry.
AB  - In this paper, we have established an efficient Legendre wavelet based
      approximation method to solve film-pore diffusion model arising in engineering.
      Film-pore diffusion model is widely used to determine study the kinetics of
      adsorption systems. The use of Legendre wavelet based approximation method is
      found to be accurate, simple, fast, flexible, convenient, and computationally
      attractive. It is shown that film-pore diffusion model satisfactorily describe
      kinetics of methylene blue adsorption onto the three low-cost adsorbents, Guava,
      teak and gulmohar plant leaf powders, used in this study. 

PMID- 24562790
TI  - Antiangiogenic therapy effects on age-associated matrix metalloproteinase-9 (MMP
      9) and insulin-like growth factor receptor-1 (IGFR-1) responses: a comparative
      study of prostate disorders in aged and TRAMP mice.
AB  - Senescence is associated with hormonal imbalance and prostatic disorders.
      Angiogenesis is fundamental for the progression of malignant lesions and is a
      promising target for prostate cancer treatment. The aim was to characterize
      matrix metalloproteinase-9 (MMP-9) and insulin-like growth factor receptor-1
      (IGFR-1) responses in the prostate during senescence and following antiangiogenic
      and/or androgen ablation therapies, comparing them to cancer progression features
      in TRAMP mice. Aged male mice (52-week-old FVB) were submitted to antiangiogenic
      treatments with SU5416 (6 mg/kg; i.p.) and/or TNP-470 (15 mg/kg; s.c).
      Finasteride (20 mg/kg; s.c.) was administered alone or associated to both
      inhibitors. Dorsolateral prostate was collected for light microscopy, and
      immunohistochemistry and Western blotting collected for MMP-9 and IGFR-1.
      Senescence led to inflammation and different proliferative lesions in the
      prostate, as well as to increased MMP-9 and IGFR-1, resembling TRAMP mice
      prostatic microenvironment. Antiangiogenic therapies promoted recovery and/or
      interruption of age-associated alterations, presenting differential effects on
      the molecules studied. SU5416 acted mainly on MMP-9, whereas TNP-470 showed its
      best influence on IGFR-1 levels. Finasteride administration, alone or in
      combination with antiangiogenic agents, also resulted in regression of
      inflammation and neoplastic lesions, besides having a negative modulatory effect
      on both MMP-9 and IGFR-1. We concluded that stimulated tissue remodeling and
      proliferative processes during senescence predisposed the prostate to malignant
      disorders. The combination of different agents was more effective to minimize
      prostatic imbalance during this period, probably due to the differential action
      of each drug on factors involved in cell proliferation and extracellular matrix
      remodeling, resulting in a broader spectrum of effects following the combined
      treatment.

PMID- 24562791
TI  - Down-regulation of the epithelial Na+ channel ENaC by Janus kinase 2.
AB  - Janus kinase-2 (JAK2), a signaling molecule mediating effects of various hormones
      including leptin and growth hormone, has previously been shown to modify the
      activity of several channels and carriers. Leptin is known to inhibit and growth
      hormone to stimulate epithelial Na(+) transport, effects at least partially
      involving regulation of the epithelial Na(+) channel ENaC. However, no published
      evidence is available regarding an influence of JAK2 on the activity of the
      epithelial Na(+) channel ENaC. In order to test whether JAK2 participates in the
      regulation of ENaC, cRNA encoding ENaC was injected into Xenopus oocytes with or
      without additional injection of cRNA encoding wild type JAK2, gain-of-function
      (V617F)JAK2 or inactive (K882E)JAK2. Moreover, ENaC was expressed with or without
      the ENaC regulating ubiquitin ligase Nedd4-2 with or without JAK2, (V617F)JAK2 or
      (K882E)JAK2. ENaC was determined from amiloride (50 MUM)-sensitive current
      (I(amil)) in dual electrode voltage clamp. Moreover, I(amil) was determined in
      colonic tissue utilizing Ussing chambers. As a result, the I(amil) in ENaC
      expressing oocytes was significantly decreased following coexpression of JAK2 or
      (V617F)JAK2, but not by coexpression of (K882E)JAK2. Coexpression of JAK2 and
      Nedd4-2 decreased I(amil) in ENaC-expressing oocytes to a larger extent than
      coexpression of Nedd4-2 alone. Exposure of ENaC- and JAK2-expressing oocytes to
      JAK2 inhibitor AG490 (40 MUM) significantly increased I(amil). In colonic
      epithelium, I(amil) was significantly enhanced by AG490 pretreatment (40 MUM, 1
      h). In conclusion, JAK2 is a powerful inhibitor of ENaC.

PMID- 24562800
TI  - Diagnostic accuracy of combined cardiac troponin and copeptin assessment for
      early rule-out of myocardial infarction: a systematic review and meta-analysis.
AB  - AIMS: This systematic review aimed to investigate the diagnostic accuracy of
      combined cardiac troponin (cTn) and copeptin assessment in comparison to cTn
      alone for early rule-out of acute myocardial infarction (AMI). METHODS: Primary
      studies were eligible if they evaluated diagnostic accuracy for cTn with and
      without copeptin in patients with symptoms suggestive of AMI. AMI was defined
      according to the universal definition, using detection of cTn as a marker for
      myocardial necrosis. Eligible studies were identified by searching electronic
      databases (Medline, EMBASE, Science Citation Index Expanded, CINAHL, Pascal, and
      Cochrane) from inception to March 2013, reviewing conference proceedings and
      contacting field experts and the copeptin manufacturer. RESULTS: In 15 studies
      totalling 8740 patients (prevalence of AMI 16%), adding copeptin improved the
      sensitivity of cTn assays (from 0.87 to 0.96, p=0.003) at the expense of lower
      specificity (from 0.84 to 0.56, p<0.001). In 12 studies providing data for 6988
      patients without ST-segment elevation, the summary sensitivity and specificity
      estimates were 0.95 (95% CI 0.89 to 0.98) and 0.57 (95% CI 0.49 to 0.65) for the
      combined assessment of cTn and copeptin. When a high-sensitivity cTnT assay was
      used in combination with copeptin, the summary sensitivity and specificity
      estimates were 0.98 (95% CI 0.96 to 1.00) and 0.50 (95% CI 0.42 to 0.58).
      CONCLUSION: Despite substantial between-study heterogeneity, this meta-analysis
      demonstrates that copeptin significantly improves baseline cTn sensitivity.
      Management studies are needed to establish the effectiveness and safety of
      measuring copeptin in combination with high-sensitivity cTnT for early rule-out
      of AMI without serial testing.

PMID- 24562799
TI  - Association between endogenous complement inhibitor and myocardial salvage in
      patients with myocardial infarction.
AB  - BACKGROUND: Many pathogenic processes and diseases are the result of an erroneous
      activation of the complement cascade and a number of inhibitors of complement
      have thus been examined for anti-inflammatory actions. It was recently
      demonstrated that supraphysiological concentrations of the endogenous complement
      inhibitor MAp44 (also denoted MAP1) protect against myocardial reperfusion
      injury. In the present study, we examined the association between outcome after
      acute myocardial infarction (MI) and the plasma levels of MAp44 and its related
      proteins MASP-1 and MASP-3 in patients with first-time MI. In addition, we
      compared plasma levels of MAp44, MASP-1, and MASP-3 in MI patients to levels in a
      healthy control group. METHODS: A total of 192 MI patients and 140 control
      persons were included. Plasma samples were obtained and analysed with time
      resolved immunofluorometric assays determining the plasma levels of MAp44, MASP
      1, and MASP-3. The myocardial outcomes (salvage index and final infarct size)
      were measured by gated single-photon emission CT. RESULTS: MI patients had 18 %
      higher plasma levels of MAp44 (IQR 11-25%) as compared to the healthy control
      group (p<0.001. However, neither salvage index (Spearman rho -0.1, p=0.28) nor
      final infarct size (Spearman rho 0.02, p=0.83) correlated with plasma levels of
      MAp44. Likewise, MASP-1 and MASP-3 were elevated in MI patients (p=0.002 and
      p<0.001), but the levels were not correlated to outcome. CONCLUSIONS: Plasma
      levels of MAp44, MASP-1, and MASP-3 are significantly higher in patients with MI
      compared to healthy control persons, but are not associated with short-term
      outcome measured as salvage index and final infarct.

PMID- 24562801
TI  - Transient attenuation of the amplitude of the QRS complexes in the diagnosis of
      Takotsubo syndrome.
AB  - BACKGROUND AND OBJECTIVES: Currently, there are no specific diagnostic
      electrocardiogram (ECG) signs for Takotsubo syndrome (TTS) to differentiate it
      from acute coronary syndromes (ACS). Myocardial oedema has been detected by
      cardiac magnetic resonance imaging in patients with TTS. Recently it has been
      postulated that myocardial oedema may be the cause of low QRS voltage (LQRSV) in
      the admission ECG and attenuation of the amplitude of the QRS complexes (AAQRS)
      in serial ECGs, noted in a few published cases of patients with TTS. The
      objective of this study was to evaluate whether the admission ECG of patients
      with documented TTS reveals LQRSV and whether AAQRS is found when serial ECGs are
      compared in such patients. METHODS: This study evaluated the prevalence of LQRSV
      in the admission ECG and AAQRS in serial ECGs in patients with TTS. ECGs of 368
      patients with TTS from published reports in the international literature were
      evaluated for LQRSV (<=5 mm in limb leads and/or <=10 mm in precordial leads) and
      AAQRS in serial ECGs. RESULTS: LQRSV was seen in 91.5% of 200 patients with TTS
      and one ECG, with a distribution of 49.0, 42.8, 51.0, 52.0, and 46.9%, in lead
      aVR, and inferior, anterior, lateral, and high lateral ECG lead groups,
      respectively. AAQRS was seen in 93.5% of 168 patients with TTS and two or more
      ECGs, with a distribution of 78.3, 74.5, 60.1, 70.7, and 74.5% in lead aVR, and
      inferior, anterior, lateral, and high lateral ECG lead groups, respectively.
      CONCLUSIONS: LQRSV and AAQRS are highly prevalent ECG signs in patients with TTS,
      and should be useful in aiding in its diagnosis and differentiation from ACS, on
      first contact with the patient on admission to the hospital, and the ensuing 24
      hours, in conjunction with echocardiography and coronary arteriography.

PMID- 24562802
TI  - Outcomes among non-ST-segment elevation acute coronary syndromes patients with no
      angiographically obstructive coronary artery disease: observations from 37,101
      patients.
AB  - AIMS: Limited data exist concerning outcomes of patients with non-ST-segment
      elevation acute coronary syndromes (NSTE ACS) with no angiographically
      obstructive coronary artery disease (non-obstructive CAD). We assessed the
      frequency of clinical outcomes among patients with non-obstructive CAD compared
      with obstructive CAD. METHODS AND RESULTS: We pooled data from eight NSTE ACS
      randomized clinical trials from 1994 to 2008, including 37,101 patients who
      underwent coronary angiography. The primary outcome was 30-day death or
      myocardial infarction (MI). Adjusted odds ratios (ORs) and 95% confidence
      intervals (CIs) for 30-day death or MI for non-obstructive versus obstructive CAD
      were generated for each trial. Summary ORs (95% CIs) across trials were generated
      using random effects models. Overall, 3550 patients (9.6%) had non-obstructive
      CAD. They were younger, more were female, and fewer had diabetes mellitus,
      previous MI or prior percutaneous coronary intervention than patients with
      obstructive CAD. Thirty-day death or MI was less frequent among patients with non
      obstructive CAD (2.2%) versus obstructive CAD (13.3%) (OR(adj) 0.15; 95% CI, 0.11
      0.20); 30-day death or spontaneous MI and six-month mortality were also less
      frequent among patients with non-obstructive CAD (OR(adj) 0.19 (0.14-0.25) and
      0.37 (0.28-0.49), respectively). CONCLUSION: Among patients with NSTE ACS, one in
      10 had non-obstructive CAD. Death or MI occurred in 2.2% of these patients by 30
      days. Compared with patients with obstructive CAD, the rate of major cardiac
      events was lower in patients with non-obstructive CAD but was not negligible,
      prompting the need to better understand management strategies for this group.

PMID- 24562803
TI  - The Seattle Post Myocardial Infarction Model (SPIM): prediction of mortality
      after acute myocardial infarction with left ventricular dysfunction.
AB  - AIMS: Ischemic heart disease is a leading worldwide cause of death. The Seattle
      Post Myocardial Infarction Model (SPIM) was developed to predict survival 6
      months to 2 years after an acute myocardial infarction with evidence of left
      ventricular dysfunction. METHODS AND RESULTS: A total of 6632 subjects from the
      EPHESUS trial were used to derive the predictive model, while 5477 subjects from
      the OPTIMAAL trial were used to validate the model. Cox proportional hazards
      modeling was used to develop a multivariate risk score predictive of all-cause
      mortality. The SPIM risk score integrated lab and vital parameters, Killip class,
      reperfusion or revascularization, the number of cardiac evidence-based medicines
      (aspirin, statin, beta blocker, ACEI/ARB, aldosterone blocker), and the number of
      cardiac risk factors. The model was predictive of all-cause mortality after
      myocardial infarction, with an AUC of 0.75 at 6 months and 0.75 at 2 years in the
      derivation cohort and 0.77 and 0.78 for the same time points in the validation
      cohort. Model predicted versus Kaplan-Meier observed survival was excellent in
      the derivation cohort. It remained so in the validation cohort--84.9% versus
      85.0% at 2 years. The 10% of subjects with the highest predicted risk had
      approximately 25 times higher mortality at 2 years than the 10% of subjects with
      the lowest predicted risk. CONCLUSION: The SPIM score was a powerful predictor of
      outcomes after myocardial infarction with left ventricular dysfunction. Its
      highly accurate predictions should improve patient and physician understanding of
      survival and may prove a useful tool in post-infarct risk stratification.

PMID- 24562806
TI  - Relationship between ST-segment resolution and anterior infarct size after
      primary percutaneous coronary intervention: analysis from the INFUSE-AMI trial.
AB  - AIMS: ST-segment resolution (STR) after reperfusion therapy has been shown to
      correlate with prognosis in patients with ST-segment elevation myocardial
      infarction (STEMI). We investigated whether acute ECG measurements also correlate
      with ultimate infarct size. METHODS AND RESULTS: The INFUSE-AMI trial randomized
      452 patients with anterior STEMI to intracoronary bolus abciximab vs. no
      abciximab, and to thrombus aspiration vs. no aspiration. Infarct size as
      percentage of total LV mass was calculated by cardiac magnetic resonance imaging
      (MRI) 30 days post intervention. Five ECG methods were analysed for their ability
      to predict MRI infarct mass: (1) summed STR across all infarct-related ECG leads
      (SigmaSTR); (2) STR in the single lead with maximum baseline ST-segment elevation
      (maxSTR); (3) summed residual ST-segment elevation across all infarct-related
      leads at 60 min post intervention (SigmaST residual); (4) maximum residual ST
      segment elevation in the worst single lead at 60 min post intervention (maxST
      residual); (5) number of new significant Q-waves (Qwave) at 60 min. All ECG
      methods strongly correlated with 30-day MRI infarct mass (all p<0.003). Simpler
      ECG measurements such as maxSTresidual and Qwave were as predictive as more
      complex measurements. A subset analysis of 158 patients who had microvascular
      obstruction (MVO) determined by MRI 5 days post intervention also showed strong
      correlations of MVO with the ECG measures. CONCLUSIONS: ST-segment and Q-wave
      changes after primary PCI in anterior STEMI strongly correlated with 30-day
      infarct size by MRI. In particular, maxST residual and Qwave at 60 min are simple
      ECG parameters that offer rapid analysis for prognostication.

PMID- 24562804
TI  - Efficacy and safety of tirofiban-supported primary percutaneous coronary
      intervention in patients pretreated with 600 mg clopidogrel: results of
      propensity analysis using the Clinical Center of Serbia STEMI Register.
AB  - BACKGROUND: Studies with platelet glycoprotein IIb/IIIa receptor inhibitors
      (GPIs) showed conflicting results in primary percutaneous coronary intervention
      (PPCI) patients who were pretreated with 600 mg clopidogrel. We sought to
      investigate the short- and long-term efficacy and safety of the periprocedural
      administration of tirofiban in a largest Serbian PPCI centre. METHODS: We
      analysed 2995 consecutive PPCI patients enrolled in the Clinical Center of Serbia
      STEMI Register, between February 2007 and March 2012. All patients were
      pretreated with 600 mg clopidogrel and 300 mg aspirin. Major adverse
      cardiovascular events, comprising all-cause death, nonfatal infarction, nonfatal
      stroke, and ischaemia-driven target vessel revascularization, was the primary
      efficacy end point. TIMI major bleeding was the key safety end point. RESULTS:
      Analyses drawn from the propensity-matched sample showed improved primary
      efficacy end point in the tirofiban group at 30-day (OR 0.72, 95% CI 0.53-0.97)
      and at 1-year (OR 0.74, 95% CI 0.57-0.96) follow up. Moreover, tirofiban group
      had a significantly lower 30-day all-cause mortality (secondary end point; OR
      0.63, 95% CI 0.40-0.90), compared with patients who were not administered
      tirofiban. At 1 year, a trend towards a lower all-cause mortality was observed in
      the tirofiban group (OR 0.74, 95% CI 0.53-1.04). No differences were found with
      respect to the TIMI major bleeding during the follow-up period. CONCLUSIONS:
      Tirofiban administered with PPCI, following 600 mg clopidogrel pretreatment,
      improved primary efficacy outcome at 30 days and at 1 year follow up without an
      increase in major bleeding.

PMID- 24562805
TI  - The prognostic importance of left ventricular function in patients with ST
      segment elevation myocardial infarction: the HORIZONS-AMI trial.
AB  - AIM: Left ventricular (LV) dysfunction during and after hospitalization for ST
      segment elevation myocardial infarction (STEMI) is associated with increased
      mortality. Whether baseline LV dysfunction impacts STEMI outcomes is not well
      studied. Furthermore, whether bivalirudin and paclitaxel-eluting stents (PES) are
      beneficial in patients with LV dysfunction is unknown. We studied the impact of
      left ventricular ejection fraction (LVEF) on outcomes of patients with STEMI in
      the HORIZONS-AMI trial. METHODS: LVEF was determined in 2648 (73.5%) of 3602
      enrolled STEMI patients, who were divided into three groups according to LV
      function: (1) severely impaired (LVEF <40%); (2) moderately impaired (LVEF 40
      50%); and (3) normal (LVEF >=50%). RESULTS: Compared to patients with normal LV
      function, those with severely impaired LVEF had higher 1-year rates of net
      adverse clinical events (27.1 vs. 14.2%, p<0.0001), major adverse cardiovascular
      events (20.7 vs. 9.5%, p<0.0001), cardiac death (10.6 vs. 1.2%, p<0.0001), and
      non-coronary artery bypass graft major bleeding (12.5 vs. 6.6%, p=0.001),
      differences which persisted after adjustment for baseline characteristics. Among
      patients with LVEF <40%, treatment with bivalirudin compared to
      heparin+GPIIb/IIIa inhibitors resulted in reduced 1-year mortality (5.8 vs.
      18.3%, p=0.007). Patients with LVEF <40% receiving PES rather than bare metal
      stents had lower rates of 1-year ischaemia-driven target lesion revascularization
      (2.9 vs. 12.6%, p=0.02) and reinfarction (4.5 vs. 14.7%, p=0.03). CONCLUSIONS:
      Among patients with STEMI undergoing primary percutaneous coronary intervention,
      adverse events are markedly increased in those with LVEF <40% during the index
      revascularization procedure. Nevertheless, these high-risk patients experience
      substantial clinical benefits from bivalirudin and PES.

PMID- 24562808
TI  - Interindividual variability in the cardiac expression of anthracycline reductases
      in donors with and without Down syndrome.
AB  - PURPOSE: The intracardiac synthesis of anthracycline alcohol metabolites (e.g.,
      daunorubicinol) contributes to the pathogenesis of anthracycline-related
      cardiotoxicity. Cancer patients with Down syndrome (DS) are at increased risk for
      anthracycline-related cardiotoxicity. We profiled the expression of anthracycline
      metabolizing enzymes in hearts from donors with- and without- DS. METHODS:
      Cardiac expression of CBR1, CBR3, AKR1A1, AKR1C3 and AKR7A2 was examined by
      quantitative real time PCR, quantitative immunoblotting, and enzyme activity
      assays using daunorubicin. The CBR1 polymorphism rs9024 was investigated by
      allelic discrimination with fluorescent probes. The contribution of CBRs/AKRs
      proteins to daunorubicin reductase activity was examined by multiple linear
      regression. RESULTS: CBR1 was the most abundant transcript (average relative
      expression; DS: 81%, non-DS: 58%), and AKR7A2 was the most abundant protein
      (average relative expression; DS: 38%, non-DS: 35%). Positive associations
      between cardiac CBR1 protein levels and daunorubicin reductase activity were
      found for samples from donors with- and without- DS. Regression analysis suggests
      that sex, CBR1, AKR1A1, and AKR7A2 protein levels were significant contributors
      to cardiac daunorubicin reductase activity. CBR1 rs9024 genotype status impacts
      on cardiac CBR1 expression in non-DS hearts. CONCLUSIONS: CBR1, AKR1A1, and
      AKR7A2 protein levels point to be important determinants for predicting the
      synthesis of cardiotoxic daunorubicinol in heart.

PMID- 24562809
TI  - Development of vorinostat-loaded solid lipid nanoparticles to enhance
      pharmacokinetics and efficacy against multidrug-resistant cancer cells.
AB  - PURPOSE: To investigate whether delivery of a histone deacetylase inhibitor,
      vorinostat (VOR), by using solid lipid nanoparticles (SLNs) enhanced its
      bioavailability and effects on multidrug-resistant cancer cells. METHODS: VOR
      loaded SLNs (VOR-SLNs) were prepared by hot homogenization using an
      emulsification-sonication technique, and the formulation parameters were
      optimized. The cytotoxicity of the optimized formulation was evaluated in cancer
      cell lines (MCF-7, A549, and MDA-MB-231), and pharmacokinetic parameters were
      examined following oral and intravenous (IV) administration to rats. RESULTS: VOR
      SLNs were spherical, with a narrowly distributed average size of ~100 nm, and
      were physically stable for 3 months. Drug release showed a typical bi-phasic
      pattern in vitro, and was independent of pH. VOR-SLNs were more cytotoxic than
      the free drug in both sensitive (MCF-7 and A549) and resistant (MDA-MB-231)
      cancer cells. Importantly, SLN formulations showed prominent cytotoxicity in MDA
      MB-231 cells at low doses, suggesting an ability to effectively counter the P
      glycoprotein-related drug efflux pumps. Pharmacokinetic studies clearly
      demonstrated that VOR-SLNs markedly improved VOR plasma circulation time and
      decreased its elimination rate constant. The areas under the VOR concentration
      time curve produced by oral and IV administration of VOR-SLNs were significantly
      greater than those produced by free drug administration. These in vivo results
      clearly highlighted the remarkable potential of SLNs to augment the
      bioavailability of VOR. CONCLUSIONS: VOR-SLNs successfully enhanced the oral
      bioavailability, circulation half-life, and chemotherapeutic potential of VOR.

PMID- 24562811
TI  - Optimal topotactic conversion of layered octosilicate to RWR-type zeolite by
      separating the formation stages of interlayer condensation and elimination of
      organic guest molecules.
AB  - We demonstrate that the separation of two stages of interlayer condensation under
      refluxing and elimination of organic guests provides the optimal conditions for
      the formation of RWR-type zeolite from layered octosilicate. The obtained RWR
      type zeolite has higher quality than any other RWR-type zeolite reported
      previously. 

PMID- 24562810
TI  - Liposomal co-delivery of omacetaxine mepesuccinate and doxorubicin for
      synergistic potentiation of antitumor activity.
AB  - PURPOSE: Anticancer chemotherapy usually involves the administration of several
      anticancer drugs that differ in their action mechanisms. Here, we aimed to test
      whether the combination of omacetaxine mepesuccinate (OMT) and doxorubicin (DOX)
      could show synergism, and whether the liposomal co-delivery of these two drugs
      could enhance their antitumor effects in cervical carcinoma model. METHOD: OMT
      loaded liposomes (OL) were prepared by loading the drug in the lipid bilayers. OL
      were then electrostatically complexed with DOX, yielding double-loaded liposomes
      (DOL). DOX-loaded liposomes (DL) were formulated by electrostatic interaction
      with negatively charged empty liposomes (EL). The combination index (CI) values
      were calculated to evaluate the synergism of two drugs. In vitro antitumor
      effects against HeLa cells were measured using CCK-8, calcein staining, and
      crystal violet staining. In vivo antitumor effects of various liposomes were
      tested using HeLa cell-bearing mice. RESULTS: Combination of DOX and OMT had
      ratio-dependent synergistic activities, with very strong synergism observed at a
      molar ratio of 4:1 (DOX:OMT). The sizes of EL, DL, OL, and DOL did not
      significantly differ, but the zeta potentials of DL and DOL were slightly higher
      than those of OL and EL. In vitro, DOL showed higher antitumor activity than OL,
      DL or EL in cervical carcinoma HeLa cells. In vivo, unlike other liposomes, DOL
      reduced the tumor growths by 98.6% and 97.3% relative to the untreated control on
      day 15 and 25 after the cessation of treatment, respectively. CONCLUSIONS: These
      results suggest that liposomal co-delivery of DOX and OMT could synergistically
      potentiate antitumor effects.

PMID- 24562812
TI  - A Bayesian method for analyzing lateral gene transfer.
AB  - Lateral gene transfer (LGT)--which transfers DNA between two non-vertically
      related individuals belonging to the same or different species--is recognized as
      a major force in prokaryotic evolution, and evidence of its impact on eukaryotic
      evolution is ever increasing. LGT has attracted much public attention for its
      potential to transfer pathogenic elements and antibiotic resistance in bacteria,
      and to transfer pesticide resistance from genetically modified crops to other
      plants. In a wider perspective, there is a growing body of studies highlighting
      the role of LGT in enabling organisms to occupy new niches or adapt to
      environmental changes. The challenge LGT poses to the standard tree-based
      conception of evolution is also being debated. Studies of LGT have, however, been
      severely limited by a lack of computational tools. The best currently available
      LGT algorithms are parsimony-based phylogenetic methods, which require a pre
      computed gene tree and cannot choose between sometimes wildly differing most
      parsimonious solutions. Moreover, in many studies, simple heuristics are applied
      that can only handle putative orthologs and completely disregard gene
      duplications (GDs). Consequently, proposed LGT among specific gene families, and
      the rate of LGT in general, remain debated. We present a Bayesian Markov-chain
      Monte Carlo-based method that integrates GD, gene loss, LGT, and sequence
      evolution, and apply the method in a genome-wide analysis of two groups of
      bacteria: Mollicutes and Cyanobacteria. Our analyses show that although the LGT
      rate between distant species is high, the net combined rate of duplication and
      close-species LGT is on average higher. We also show that the common practice of
      disregarding reconcilability in gene tree inference overestimates the number of
      LGT and duplication events.

PMID- 24562813
TI  - The emergence of lobsters: phylogenetic relationships, morphological evolution
      and divergence time comparisons of an ancient group (decapoda: achelata,
      astacidea, glypheidea, polychelida).
AB  - Lobsters are a ubiquitous and economically important group of decapod crustaceans
      that include the infraorders Polychelida, Glypheidea, Astacidea and Achelata.
      They include familiar forms such as the spiny, slipper, clawed lobsters and
      crayfish and unfamiliar forms such as the deep-sea and "living fossil" species.
      The high degree of morphological diversity among these infraorders has led to a
      dynamic classification and conflicting hypotheses of evolutionary relationships.
      In this study, we estimated phylogenetic relationships among the major groups of
      all lobster families and 94% of the genera using six genes (mitochondrial and
      nuclear) and 195 morphological characters across 173 species of lobsters for the
      most comprehensive sampling to date. Lobsters were recovered as a non
      monophyletic assemblage in the combined (molecular + morphology) analysis. All
      families were monophyletic, with the exception of Cambaridae, and 7 of 79 genera
      were recovered as poly- or paraphyletic. A rich fossil history coupled with dense
      taxon coverage allowed us to estimate and compare divergence times and origins of
      major lineages using two drastically different approaches. Age priors were
      constructed and/or included based on fossil age information or fossil discovery,
      age, and extant species count data. Results from the two approaches were largely
      congruent across deep to shallow taxonomic divergences across major lineages. The
      origin of the first lobster-like decapod (Polychelida) was estimated in the
      Devonian (~409-372 Ma) with all infraorders present in the Carboniferous (~353
      318 Ma). Fossil calibration subsampling studies examined the influence of
      sampling density (number of fossils) and placement (deep, middle, and shallow) on
      divergence time estimates. Results from our study suggest including at least 1
      fossil per 10 operational taxonomic units (OTUs) in divergence dating analyses.
      [Dating; decapods; divergence; lobsters; molecular; morphology; phylogenetics.]. 

PMID- 24562814
TI  - Success, failure, and spreading speeds for invasions on spatial gradients.
AB  - We study a model that describes the spatial spread of a species along a habitat
      gradient on which the species' growth increases. Mathematical analysis is
      provided to determine the spreading dynamics of the model. We demonstrate that
      the species may succeed or fail in local invasion depending on the species'
      growth function and dispersal kernel. We delineate the conditions under which a
      spreading species may be stopped by poor quality habitat, and demonstrate how a
      species can escape a region of poor quality habitat by climbing a resource
      gradient to good quality habitat where it spreads at a constant spreading speed.
      We show that dispersal may take the species from a good quality region to a poor
      quality region where the species becomes extinct. We also provide formulas for
      spreading speeds for the model that are determined by the dispersal kernel and
      linearized growth rates in both directions. 

PMID- 24562815
TI  - Acute impacts of the deer ked (Lipoptena cervi) infestation on reindeer (Rangifer
      tarandus tarandus) behaviour.
AB  - Blood-sucking ectoparasites have often a strong impact on the behaviour of their
      hosts. The annual insect harassment of reindeer (Rangifer tarandus tarandus) has
      increased in the southern part of the Finnish reindeer herding area because of
      the recent invasion of a blood-feeding ectoparasitic louse-fly, the deer ked
      (Lipoptena cervi). We studied the impact of the deer ked on the behaviour of
      reindeer. Twelve reindeer were infested with a total of 300 keds/reindeer on six
      occasions in a 5-week period during the deer ked flight season in autumn, while
      six non-infested reindeer were used as controls. Behavioural patterns indicating
      potential stress were monitored by visual observation from August to December.
      The infested reindeer displayed more incidences of restless behaviour than the
      controls. Shaking and scratching were the most common forms of restless behaviour
      after infestation of deer keds. Increased grooming was also observed after the
      transplantation and also later, 1 month after the infestation. Based on the
      results, the deer ked infestation can cause acute behavioural disturbance in
      reindeer and, thus, could pose a potential threat to reindeer welfare.
      Antiparasitic treatment with, e.g. ivermectin, may increase the welfare of
      parasitized reindeer by reducing deer keds. If the deer ked infestation intensity
      on the reindeer herding area increases and restless behaviour of reindeer becomes
      more common, the present results can help in further evaluation of the duration
      and magnitude of behavioural changes.

PMID- 24562816
TI  - Pathogenicity of Nc-Bahia and Nc-1 strains of Neospora caninum in experimentally
      infected cows and buffaloes in early pregnancy.
AB  - Neospora caninum is a protozoan parasite known as an important cause of bovine
      abortion worldwide. Little is currently known about how different strains of N.
      caninum vary in their pathogenicity. In this study, we compared a Brazilian
      strain, Nc-Bahia, with the first isolate of this coccidian, Nc-1. Eight cows and
      seven buffaloes were submitted to fixed-time artificial insemination protocols
      for a better control of pregnancy. Group 1 was inoculated with Nc-Bahia (n = 8;
      five cows and three buffaloes), and Group 2 was inoculated with Nc-1 (n = 5; two
      cows and three buffaloes). One nonpregnant female of each species was left
      uninfected as sentinel controls for potential environmental infection. All
      inoculated animals received 5 * 10(8) tachyzoites of N. caninum, by intravenous
      route, on the 70th day of gestation. Uninfected animals remained seronegative
      throughout the experiment, indicating no exogenous infection, whereas all
      inoculated animals became seropositive to N. caninum. In Group 1, abortion was
      found in only one cow on 42 days postinfection (dpi; frequency of abortion =
      12.5%), whilst all animals from Group 2 aborted on 35 dpi (frequency of abortion
      = 100%). Parasite DNA was detected by seminested PCR in maternal, foetal and
      placental tissues, confirming vertical transmission in Groups 1 and 2, although
      histological lesions had different frequencies and degrees of severity between
      the groups. There was evidence of lower pathogenicity of Nc-Bahia compared to Nc
      1 when used in experimental infection, as it caused fewer abortions, as well as
      less frequent and milder histological lesions. This was the first time Nc-Bahia
      has been used for experimental infection.

PMID- 24562817
TI  - Two new species of Maritrema Nicoll, 1907 (Digenea: Microphallidae) from New
      Zealand: morphological and molecular characterisation.
AB  - Two new species of the microphallid genus Maritrema (Maritrema) Nicoll, 1907 are
      described from freshwaters in the South Island of New Zealand. Maritrema deblocki
      n. sp. occurs as an adult in the mallard Anas platyrhynchos (L.); Maritrema
      poulini n. sp. is found as sporocysts/cercariae in Potamopyrgus antipodarum
      (Gray) and as metacercariae in two species of amphipod and two species of isopod.
      We use morphological and molecular characterisation to distinguish between the
      two species, and compare them to their four morphologically closest congeners. M.
      deblocki n. sp. and M. poulini n. sp. are distinguished from each other by the
      relative sucker size, the positions of the genital pore and ovary, the
      convergence of the vitelline ribbons, and overall size. With the aid of molecular
      data, we matched life cycle stages of M. poulini n. sp. and assessed its use of
      multiple second intermediate hosts. Phylogenetic analyses included sequences for
      the two new species and the available microphallid sequences for the large
      ribosomal subunit and the internal transcribed spacer 1 of the ribosomal RNA
      gene. Closer to each other than to any other species, the sister species together
      with Maritrema novaezealandense Martorelli, Fredensborg, Mouritsen & Poulin,
      2004, Maritrema heardi (Kinsella & Deblock, 1994), Maritrema eroliae Yamaguti,
      1939 and Maritrema oocysta (Lebour, 1907) formed a well-supported clade. In
      addition, we clarify the taxonomic identity of several unidentified Microphallus
      spp. in the recent ecological literature from New Zealand and propose corrected
      spellings for a number of Maritrema species epithets. 

PMID- 24562819
TI  - Other factors may effect the relationship between heart rate variability indices
      and coronary atherosclerosis.

PMID- 24562820
TI  - Response to Kurtoglu and Balta.

PMID- 24562818
TI  - Biological activity and migration of wear particles in the knee joint: an in vivo
      comparison of six different polyethylene materials.
AB  - Wear of polyethylene causes loosening of joint prostheses because of the particle
      mediated activity of the host tissue. It was hypothesized that conventional and
      crosslinked polyethylene particles lead to similar biological effects around the
      knee joint in vivo as well as to a similar particle distribution in the
      surrounding tissues. To verify these hypotheses, particle suspensions of six
      different polyethylene materials were injected into knee joints of Balb/C mice
      and intravital microscopic, histological and immunohistochemical evaluations were
      done after 1 week. Whereas the biological effects on the synovial layer and the
      subchondral bone of femur and tibia were similar for all the polyethylenes, two
      crosslinked materials showed an elevated cytokine expression in the articular
      cartilage. Furthermore, the distribution of particles around the joint was
      dependent on the injected polyethylene material. Those crosslinked particles,
      which remained mainly in the joint space, showed an increased expression of TNF
      alpha in articular cartilage. The data of this study support the use of
      crosslinked polyethylene in total knee arthroplasty. In contrast, the presence of
      certain crosslinked wear particles in the joint space can lead to an elevated
      inflammatory reaction in the remaining cartilage, which challenges the potential
      use of those crosslinked polyethylenes for unicondylar knee prostheses.

PMID- 24562822
TI  - Performance profile of a FDG-PET cancer screening program for detecting gastric
      cancer: results from a nationwide Japanese survey.
AB  - PURPOSE: It has been reported that gastric cancer is the sixth most common cancer
      found during the (18)F-fluorodeoxyglucose-positron emission tomography (FDG-PET)
      cancer screening program, which is defined as cancer screening of asymptomatic
      subjects using FDG-PET(/CT) (in combination with other screening tests or not).
      The aim of this study was to analyze the detection rate and the effectiveness of
      the FDG-PET cancer screening program at detecting gastric cancer between 2006 and
      2009 in Japan. MATERIALS AND METHODS: A total of 153,775 asymptomatic subjects
      (92,255 men, 61,520 women) between 30 and 80 years old underwent the FDG-PET
      cancer screening program. Of these, we analyzed 790 cases with findings of
      possible gastric cancer in any screening test. RESULTS: The number of cases who
      were verified to have gastric cancer was 124. Among these, only 47 cases were
      detected by FDG-PET, which resulted in a relative sensitivity of 37.9% and a
      positive predictive value of 33.6%. The relative sensitivity of FDG-PET was much
      lower than those of gastric endoscopy and the serum pepsinogen test. CONCLUSION:
      The FDG-PET screening program in Japan detected some cases of early-stage gastric
      cancer, but this was not achieved using FDG-PET alone but in combination with
      gastric endoscopy. Gastric endoscopy should be included in FDG-PET cancer
      screening programs to screen for gastric cancer.

PMID- 24562823
TI  - Optimum duration of neoadjuvant letrozole to permit breast conserving surgery.
AB  - The aim of this multicenter, prospective, longitudinal phase IV study was to
      establish the optimal duration of neoadjuvant letrozole that would allow breast
      conservation surgery (BCS) in patients with early breast cancer who were
      initially unsuitable. Primary, invasive, estrogen-receptor- and/or progesterone
      receptor-positive breast cancer patients, with large tumors (>=T2 i.e., >20 mm)
      not initially suitable for BCS, received 2.5 mg letrozole p.o. daily. Patients
      continued treatment until they became eligible for BCS, progressed, failed to
      meet criteria for BCS and withdrew for scheduled mastectomy, withdrew for other
      reasons, or completed 12 months of letrozole treatment without a BCS decision
      being made. A total of 146 patients were enrolled; seven patients who did not
      have a valid postbaseline tumor assessment were excluded from the final efficacy
      analysis. At study closure, 69 % of patients (96 of 139) were eligible for BCS.
      The median time to achieve a tumor response sufficient to allow BCS with
      neoadjuvant letrozole was 7.5 months (95 % CI 6.3-8.5 months). Letrozole was well
      tolerated, and most adverse events were mild-to-moderate (grade 1-2). The results
      from this trial suggest that extended letrozole therapy in the neoadjuvant
      setting (7.5 months), as opposed to conventional treatment of 4 months, is
      optimal to achieve maximum reduction in tumor volume sufficient for BCS.

PMID- 24562821
TI  - The role of cold shock domain proteins in inflammatory diseases.
AB  - Cold shock domain proteins are characterized by the presence of one or more
      evolutionarily conserved cold shock domains, which each possess two nucleic acid
      binding motifs. These proteins exert pleiotropic functions in cells via their
      ability to bind single-stranded RNA and/or DNA, thus allowing them to serve as
      transcriptional as well as translational regulators. Not only can they regulate
      their own expression, but they also regulate the expression of a number of pro-
      and anti-inflammatory cytokines, as well as cytokine receptors, making them key
      players in the orchestration of inflammatory processes and immune cell
      phenotypes. To add to their complexity, the expression of cold shock domain
      proteins is induced by cellular stress. At least one cold shock domain protein is
      actively secreted and binds to specific cell surface receptors, thereby
      influencing the proliferative and migratory capacity of the cell. The presence of
      cold shock domain proteins in the blood and/or urine of patients with cancer or
      inflammatory disease, as well as the identification of autoantibodies directed
      against these proteins make them potential targets of therapeutic interest. 

PMID- 24562824
TI  - Expert perspectives on biosimilar monoclonal antibodies in breast cancer.
AB  - While biosimilars of low molecular-weight biologics such as G-CSF have been
      available in Europe since 2006, biosimilars of monoclonal antibodies (mAbs) have
      only become available in the last year. Unlike G-CSF, mAbs are large and complex
      and often play a direct role in the survival of patients with life-threatening
      illnesses such as breast cancer. Several biosimilars are currently under
      development for the treatment of breast cancer, and the use of biosimilars in a
      setting that directly impacts patient survival raises a number of questions. In
      this review, we discuss the biosimilar mAbs currently in development for the
      treatment of breast cancer. We provide an overview of the European Medicine
      Agency guidelines and historic data on the development of biosimilars in order to
      discuss the development of biosimilar mAbs for breast cancer. Biosimilars offer a
      highly attractive path toward reducing the cost of medical care and should be
      pursued with great interest. However, for agents used to treat life-threatening
      diseases such as cancer, a cautious approach must be taken to ensure that there
      is no negative impact on patient care. Clinical trials for biosimilar mAbs must
      be carried out in an appropriately sensitive patient population using endpoints
      that can accurately demonstrate both the similarity of the biosimilar and its
      efficacy in the indication. Due to the abbreviated approval pathway, rigorous
      pharmacovigilance must be in place once a biosimilar mAb is approved in order to
      ensure its long-term safety and efficacy.

PMID- 24562825
TI  - Activist engineering: changing engineering practice by deploying praxis.
AB  - In this paper, we reflect on current notions of engineering practice by examining
      some of the motives for engineered solutions to the problem of climate change. We
      draw on fields such as science and technology studies, the philosophy of
      technology, and environmental ethics to highlight how dominant notions of
      apoliticism and ahistoricity are ingrained in contemporary engineering practice.
      We argue that a solely technological response to climate change does not question
      the social, political, and cultural tenet of infinite material growth, one of the
      root causes of climate change. In response to the contemporary engineering
      practice, we define an activist engineer as someone who not only can provide
      specific engineered solutions, but who also steps back from their work and
      tackles the question, What is the real problem and does this problem "require" an
      engineering intervention? Solving complex problems like climate change requires
      radical cultural change, and a significant obstacle is educating engineers about
      how to conceive of and create "authentic alternatives," that is, solutions that
      differ from the paradigm of "technologically improving" our way out of problems.
      As a means to realize radically new solutions, we investigate how engineers might
      (re)deploy the concept of praxis, which raises awareness in engineers of the
      inherent politics of technological design. Praxis empowers engineers with a more
      comprehensive understanding of problems, and thus transforms technologies, when
      appropriate, into more socially just and ecologically sensitive interventions.
      Most importantly, praxis also raises a radical alternative rarely considered-not
      "engineering a solution." Activist engineering offers a contrasting method to
      contemporary engineering practice and leads toward social justice and ecological
      protection through problem solving by asking not, How will we technologize our
      way out of the problems we face? but instead, What really needs to be done?

PMID- 24562837
TI  - One-leg standing time and hip-fracture prediction.
AB  - A hip fracture results in a lower quality of life and a cost of L30,000. In this
      study, one-leg standing time (OLST) had a negative linear relationship to the
      risk of a hip fracture. OLST could be a useful tool to assess the need for
      fracture-preventive interventions. INTRODUCTION: A hip fracture immobilizes,
      restricts autonomy, shortens life expectancy, and results in a cost of L30,000 in
      the UK health care system. However, effective preventive treatments can be
      offered to high-risk individuals. Impaired postural balance is an important risk
      factor for hip fractures, and the aim of this study was to evaluate whether OLST
      can predict hip fractures in elderly women. FRAX is the most established fracture
      risk assessment tool worldwide and a secondary aim was to relate the predictive
      ability of OLST to that of FRAX in this population. METHODS: Three hundred fifty
      one women aged between 69 and 79 years were timed standing on one leg up to 30 s
      with eyes open and assessed with FRAX. Fracture data was obtained from registers.
      RESULTS: The main outcome, a hip fracture, occurred in 40 of the 351 participants
      (11.4%). The age-adjusted risk of a hip fracture was 5% lower with 1 s longer
      OLST (Hazard ratio 0.95, 95% CI 0.927-0.978). The relation between OLST and hip
      fracture risk was linear. Harrell's c was 0.60 for FRAX and 0.68 for OLST
      adjusted for age. CONCLUSION: With 1 s longer OLST, the risk of a hip fracture
      decreased significantly by 5%. This risk reduction was not explained by
      differences in the classic fracture risk factors included in FRAX. OLST had a
      predictive ability similar to FRAX. OLST is an easily performed balance test
      which may prove to be valuable in the assessment of hip fracture risk.

PMID- 24562838
TI  - An increase in the incidence of hip fractures in Tangshan, China.
AB  - We determined the number and incidence of hip fractures in Tangshan, China, in
      2010. Compared with data we reported in Tangshan from 1994, the crude and age
      specific incidence increased significantly for both sexes, especially in women.
      Strategies are needed for effective fracture prevention in the future.
      INTRODUCTION: The aims of the study were to determine the incidence of cervical
      and trochanteric fractures of the proximal femur in Tangshan, China, in 2010 and
      to compare the incidence with data from 1994. METHODS: The orthopedic departments
      of 15 hospitals in Tangshan were visited in 2010; the medical records and
      radiographs of patients who had sustained cervical and trochanteric fractures
      were reviewed. The absolute number of admissions was collated and the incidence
      rate per 100,000 person years was calculated, adjusted by different age ranges,
      and gender. We then calculated the age-standardized incidence in 2010 as compared
      with those from 1994. RESULTS: The population of Tangshan in 2010 was determined
      to be 3,075,382 (1,558,173 males; 1,517,209 females); there were 1,509 cervical
      and trochanteric fractures (in 745 males and 764 females). The overall incidence
      was 47.8 and 50.4 fractures per 100,000 per year for men and women, respectively.
      Females showed a higher fracture incidence than males in those aged 55 years and
      over. Comparing the 2010 data with the 1994 findings, the incidence increased by
      85% in men and by 306% in women; age-specific increases were observed in all
      female and male groups (except the 55-59 years age group). CONCLUSIONS: Compared
      with the results in 1994, the incidence of hip fracture has markedly increased in
      2010 in Tangshan, China. It is necessary to implement a comprehensive policy for
      hip fracture prevention in our communities.

PMID- 24562839
TI  - Comparison of two commercially available ELISAs for circulating sclerostin.
AB  - This study investigates the performance and correlation of sclerostin
      measurements by two commercially available sclerostin ELISAs from TECOmedical and
      Biomedica. We found that the correlation between the results of two sclerostin
      assays is strong. INTRODUCTION: Circulating sclerostin levels may provide insight
      into the pathophysiology of metabolic bone diseases such as osteoporosis.
      However, recent studies suggest that commercially available assays give different
      results. We compare the analytical performance of the two most used commercially
      available sclerostin ELISAs from TECOmedical and Biomedica. METHODS: Sclerostin
      levels were assessed in 20 paired serum, EDTA, and heparin plasma convenience
      samples from hospitalized patients. In addition, sclerostin was measured in serum
      samples from 34 patients with metabolic bone diseases and from 10 patients with
      chronic kidney disease (CKD). Samples from three healthy donors were used to
      determine stability and intra- and inter- assay precision. RESULTS: The average
      serum sclerostin concentration of all patients (n = 64) was 0.713 +/- 0.58 ng/mL
      with the Biomedica assay and 0.734 +/- 0.43 ng/mL with the TECO assay (p < 0.05).
      The results correlated strongly (r = 0.9; p < 0.0001), with Passing-Bablok
      regression showing a linear relationship but with a slight systematic and
      proportional difference between both assays. Sclerostin levels were about 30%
      higher in plasma than in serum for both assays, while no significant difference
      was seen between EDTA and heparin plasma. Intra- and inter- precision were <10%
      for TECO and <20% for Biomedica. Samples were stable for up to three freeze-thaw
      cycles with both assays. CONCLUSIONS: The two commercially available ELISAs for
      measuring circulating levels of sclerostin are comparable. However, given the
      small but statistically significant systematic and proportional differences
      between both assays, results and reference ranges will be assay-specific. Results
      will also be specific to serum or plasma.

PMID- 24562840
TI  - A systematic review and meta-analysis of utility-based quality of life for
      osteoporosis-related conditions.
AB  - This study aimed to statistically combine multiple health state utility values
      (HSUVs) reported in the literature for patients with osteoporosis and
      osteoporotic fractures. Fracture events were associated with decrements in HSUVs
      which differed between fracture sites. We have provided summary values for use in
      future health economics analyses in osteoporosis. Osteoporotic fractures have
      high financial and health burden. Economic evaluations on osteoporotic fracture
      prevention have been frequently performed in past decades. One of the challenges
      in the economic evaluations was to identify consistent health state utility
      values (HSUVs) to use for osteoporotic fracture-related conditions. The objective
      of this study was to determine summary measures of multiple HSUVs reported in the
      literature for patients with osteoporosis and osteoporotic fractures. We
      performed a systematic review, meta-analysis and meta-regression of published
      literature that reported HSUVs for osteoporotic fracture-related conditions.
      There were 62 studies representing 142,477 patients included. In total, 362 HSUVs
      were identified: 106 for pre-fracture; 89 for post-hip fracture; 130 for post
      vertebral fracture and 37 for post-wrist fracture. The pooled HSUVs, using a
      random-effects model were 0.76 (95% CI 0.75, 0.77, I (2) = 0.99) for pre
      fracture; 0.57 (95% CI 0.52, 0.63, I (2) =1) for post-hip fracture; 0.59 (95% CI
      0.55, 0.62, I (2) = 0.99) for post-vertebral facture and 0.72 (95% CI 0.67, 0.78,
      I (2) = 1) for post-wrist fracture. Heterogeneities were addressed through meta
      regression. HSUVs immediately following hip, vertebral and wrist fractures were
      0.31, 0.44 and 0.61, respectively. Patients' HSUVs improved over time following
      fracture events: HSUVs for the first year after hip, vertebral and wrist
      fractures were 0.59, 0.55 and 0.78, respectively; and 0.66, 0.66 and 0.81 for
      subsequent years. Fractures were associated with significant decrements in HSUVs.
      This study provides a standard set of HSUVs that can be used in health economic
      assessments in osteoporosis.

PMID- 24562850
TI  - Free vascularised fibular grafts in orthopaedics.
AB  - Bony defects caused by trauma, tumors, infection or congenital anomalies can
      present a significant surgical challenge. Free vascularised fibular bone grafts
      (FVFGs) have proven to be extremely effective in managing larger defects (longer
      than 6 cm) where other conventional grafts have failed. FVFGs also have a role in
      the treatment of avascular necrosis (AVN) of the femoral head, failed spinal
      fusions and complex arthrodeses. Due to the fact that they have their own blood
      supply, FVFGs are effective even in cases where there is poor vascularity at the
      recipient site, such as in infection and following radiotherapy. This article
      discusses the versatility of the FVFG and its successful application to a variety
      of different pathologies. It also covers the applied anatomy, indications,
      operative techniques, complications and donor-site morbidity. Though technically
      challenging and demanding, the FVFG is an extremely useful salvage option and can
      facilitate limb reconstruction in the most complex of cases.

PMID- 24562851
TI  - Experimental and theoretical assignment of the vibrational spectra of triazoles
      and benzotriazoles. Identification of IR marker bands and electric response
      properties.
AB  - The FTIR spectra of a series of 1H- and 2H- 1,2,3- and 1,2,4- triazoles and
      benzotriazoles were measured in the solid state. Assignments of the observed
      bands were facilitated by computation of the spectra using the density functional
      B3LYP method with the 6-311++G** basis set. The theoretical spectra show very
      good agreement with experiment. Rigorous normal coordinate analyses have been
      performed, and detailed vibrational assignment has been made on the basis of the
      calculated potential energy distributions. Several ambiguities and contradictions
      in the previously reported vibrational assignments have been clarified. "Marker
      bands" characterize the triazole ring were identified. The effect of
      substituents, the nature of the characteristic "marker bands" and quenching of
      intensities of some bands are discussed. Comparison of the topology of the charge
      density distribution, and the electric response properties of the 1H-, and 2H-
      isomers of both 1,2,3- and 1,2,4 triazole have been made using the quantum theory
      of atoms-in-molecules (QTAIM) by calculating the Laplacian of the electron
      density (?2rho(r)). Analysis of the contour plots and relief maps of ?2rho(r)
      reveals that 1,2,3- and 1,2,4-triazoles show completely different topological
      features for the distribution of the electron density. Thus, while the 1,2,3
      isomer is a very polar molecule, the 1,2,4-isomer is much more polarizable.
      Bonding characteristics show also different features. This would thus underlie
      the different features of their vibrational spectra. The reported vibrational
      assignment can be used for further spectroscopic studies of new drugs and
      biological compounds containing the triazole ring.

PMID- 24562854
TI  - Charge distribution analysis in Ag(n)(m+) clusters: molecular modeling and DFT
      calculations.
AB  - Neutral and charged silver clusters Ag63(m+) and Ag113(m+) (m=0,...,20) are
      investigated by simulated annealing molecular dynamics simulations. With
      increasing charge to size ratio the clusters undergo deformation to better
      accommodate surface charges. The latter are heterogeneously distributed and
      reflect the interplay of overall electrostatic repulsion and different degrees of
      local under-coordination of surface atoms. By comparison with atomic charges from
      natural population analysis based on density-functional calculations we
      demonstrate the suitability of the embedded-atom force-field in combination with
      the charge equilibrium approach.

PMID- 24562852
TI  - UV-vis absorption spectrum of a novel Ru(II) complex intercalated in DNA:
      [Ru(2,2'-bipy)(dppz)(2,2'-ArPy)]+.
AB  - The synthesis of a new Ru(II) complex is reported. Its absorption spectrum when
      interacting with DNA in water was calculated at the hybrid quantum mechanics
      molecular mechanics level of theory and compared with experimental data. The
      vertical transitions were computed using time-dependent density functional theory
      in the linear response approximation. The complex and its environment were
      treated at the quantum mechanical and molecular mechanical levels, respectively.
      The effects of the environment were investigated in detail and conveniently
      classified into electrostatic and polarization effects. The latter were modeled
      using the computationally inexpensive "electronic response of the surroundings"
      method. It was found that the main features of the experimental spectrum are
      nicely reproduced by the theoretical calculations. Moreover, analysis of the most
      intense transitions utilizing the natural transition orbital formalism revealed
      important insights into their nature and their potential role in the irreversible
      oxidation of DNA, a phenomenon that could be relevant in the field of cancer
      therapy.

PMID- 24562853
TI  - Experimental and theoretical study of the mechanism of hydrolysis of substituted
      phenyl hexanoates catalysed by globin in the presence of surfactant.
AB  - The bimolecular rate constants for the globin- and alkali-catalysed hydrolysis of
      substituted phenyl hexanoates in the absence and presence of
      cetyltrimethylammonium bromide (CTAB) obey Bronsted equations with beta(lg) = 
      0.53 (globin-catalysed), -0.68 (globin-catalysed in CTAB), -0.34 (in water) and 
      0.74 (in CTAB), respectively. The slopes indicate that the microsolvation
      environments associated with the transition states of the catalysed reactions are
      different from those that occur in aqueous medium. The slope (-0.74) for the
      reaction in CTAB implies that it proceeds in a less polar medium. The larger
      beta(lg) value (-0.53) obtained for the globin-catalysed reaction compared to
      that for the uncatalysed one may be attributed to either the less polar
      microenvironments of the transition states or the involvement of one of the
      imidazole groups as a nucleophile. The results from a study of the effect of pH
      on the reactivity provide evidence for the latter assumption. All of the ligands
      were docked into the hydrophobic pocket of the protein, and the resulting docking
      scores ranged from -30.76 to -23.61 kcal mol-1. Molecular dynamic simulations and
      MM-PBSA/GBSA calculations performed for the complexes gave insight into the
      binding modes of globin to the esters, which are consistent with experimental
      results. The calculations yielded comparable free energies of binding to the
      experimental ones for 4-nitrophenyl and 4-chloro-2-nitrophenyl hexanoates. In
      conclusion, information obtained from the linear free-energy relationship is
      still very useful for elucidating the mechanisms of organic reactions, including
      enzyme-catalysed reactions. This approach is further supported by the utilization
      of computational tools.

PMID- 24562855
TI  - Homology modeling and virtual screening for antagonists of protease from yellow
      head virus.
AB  - Yellow head virus (YHV) is one of the causative agents of shrimp viral disease.
      The prevention of YHV infection in shrimp has been developed by various methods,
      but it is still insufficient to protect the mass mortality in shrimp. New
      approaches for the antiviral drug development for viral infection have been
      focused on the inhibition of several potent viral enzymes, and thus the YHV
      protease is one of the interesting targets for developing antiviral drugs
      according to the pivotal roles of the enzyme in an early stage of viral
      propagation. In this study, a theoretical modeling of the YHV protease was
      constructed based on the folds of several known crystal structures of other viral
      proteases, and was subsequently used as a target for virtual screening-molecular
      docking against approximately 1364 NCI structurally diversity compounds. A
      complex between the protease and the hit compounds was investigated for
      intermolecular interactions by molecular dynamics simulations. Five best
      predicted compounds (NSC122819, NSC345647, NSC319990, NSC50650, and NSC5069) were
      tested against bacterial expressed YHV. The NSC122819 showed the best inhibitory
      characteristic among the candidates, while others showed more than 50 % of
      inhibition in the assay condition. These compounds could potentially be
      inhibitors for curing YHV infection. 

PMID- 24562858
TI  - An all-atom force field developed for Zn4O(RCO2)6 metal organic frameworks.
AB  - An all-atom force field is developed for metal organic frameworks Zn4O(RCO2)6 by
      fitting to quantum mechanics data. Molecular simulations are conducted to
      validate the force field by calculating thermal expansion coefficients, crystal
      bulk and Young's moduli, power spectra, self-diffusion coefficients, and
      activation energies of self-diffusions for benzene and n-hexane. The calculated
      results are in good agreement with available experimental data. The proposed
      force field is suitable for simulations of adsorption or diffusion of organic
      molecules with flexible frameworks.

PMID- 24562856
TI  - Insights into the influence of 5-HT2c aminoacidic variants with the inhibitory
      action of serotonin inverse agonists and antagonists.
AB  - Specific modulation of serotonin 5-HT(2C) G protein-coupled receptors may be
      therapeutic for obesity and neuropsychiatric disorders. The different efficacy of
      drugs targeting these receptors are due to the presence of genetic variants in
      population and this variability is still hard to predict. Therefore, in order to
      administer the more suitable drug, taking into account patient genotype, it is
      necessary to know the molecular effects of its gene nucleotide variations. In
      this work, starting from an accurate 3D model of 5-HT(2C), we focus on the
      prediction of the possible effect of some single nucleotide polymorphisms (SNPs)
      producing amino acidic changes in proximity of the 5-HT(2C) ligand binding site.
      Particularly we chose a set of 5-HT(2C) inverse agonists and antagonists which
      have high inhibitory activity. After prediction of the structures of the receptor
      ligand complexes using molecular docking tools, we performed full atom molecular
      dynamics simulations in explicit lipid bilayer monitoring the interactions
      between ligands and trans-membrane helices of the receptor, trying to infer
      relations with their biological activity. Serotonin, as the natural ligand was
      chosen as reference compound to advance a hypothesis able to explain the receptor
      inhibition mechanism. Indeed we observed a different behavior between the
      antagonists and inverse agonist with respect to serotonin or unbounded receptor,
      which could be responsible, even if not directly, of receptor's inactivation.
      Furthermore, we analyzed five aminoacidic variants of 5HT(2C) receptor observing
      alterations in the interactions between ligands and receptor which give rise to
      changes of free energy values for every complex considered.

PMID- 24562857
TI  - Nanomechanics of beta-rich proteins related to neuronal disorders studied by AFM,
      all-atom and coarse-grained MD methods.
AB  - Computer simulations of protein unfolding substantially help to interpret force
      extension curves measured in single-molecule atomic force microscope (AFM)
      experiments. Standard all-atom (AA) molecular dynamics simulations (MD) give a
      good qualitative mechanical unfolding picture but predict values too large for
      the maximum AFM forces with the common pulling speeds adopted here. Fine tuned
      coarse-grain MD computations (CG MD) offer quantitative agreement with
      experimental forces. In this paper we address an important methodological aspect
      of MD modeling, namely the impact of numerical noise generated by random
      assignments of bead velocities on maximum forces (F(max)) calculated within the
      CG MD approach. Distributions of CG forces from 2000 MD runs for several model
      proteins rich in beta structures and having folds with increasing complexity are
      presented. It is shown that F(max) have nearly Gaussian distributions and that
      values of F(max) for each of those beta-structures may vary from 93.2 +/- 28.9 pN
      (neurexin) to 198.3 +/- 25.2 pN (fibronectin). The CG unfolding spectra are
      compared with AA steered MD data and with results of our AFM experiments for
      modules present in contactin, fibronectin and neurexin. The stability of these
      proteins is critical for the proper functioning of neuronal synaptic clefts. Our
      results confirm that CG modeling of a single molecule unfolding is a good
      auxiliary tool in nanomechanics but large sets of data have to be collected
      before reliable comparisons of protein mechanical stabilities are made.

PMID- 24562859
TI  - A computational model of the glycine tautomerization reaction in aqueous
      solution.
AB  - A theoretical study of the internal proton transfer reaction of glycine (Gly) in
      aqueous solution was performed by means of steered molecular dynamics (SMD)
      simulation with solute-solvent interaction potentials derived from AMBER van der
      Waals parameters and QM/MM electrostatic charges in solution. Thermodynamic
      calculations and the analysis of the solvation structure, dynamic properties, and
      vibrational spectra associated with the species involved in the tautomerization
      process were performed. The results obtained for the Gibbs free energy activation
      and reaction (DeltaG(?) =5.28 kcal mol-1 and DeltaG(R)=-6.65 kcal mol-1), the
      solute-solvent interaction energy of the different glycine structures, and the
      hydrogen-bond lifetimes are in agreement with previous studies. These hydrations
      drive an increase in the diffusion coefficient and a decrease in the time of
      reorientation when the process takes place in the direction Z-Gly -> TS-Gly -> N
      Gly. The vibrational spectrum associated with the normal modes of the bridge
      hydrogen atoms shows the N-H stretching at nu(s)=3,470 cm-1 and nu(as)=3,470 cm
      1, the O-H stretching at 3,205 cm-1, and the NHO bending at about 1,400 cm-1, in
      agreement with previously reported data.

PMID- 24562860
TI  - Stereodynamic study of the reaction H(2S) + ClO(2Pi) -> HO(2Pi) + Cl(2P) via
      quasi-classical trajectory calculations.
AB  - Quasi-classical trajectory calculations were performed to investigate the
      stereodynamics of the reaction H(2S) + ClO(2Pi) -> HO(2Pi) + Cl(2P) using the
      ground-state potential energy surface 11A'. The alignment and orientation of the
      product molecules as well as the four polarization-dependent differential cross
      sections (PDDCSs) for this reaction across a wide range of collision energies
      (0.05-1.0 eV) and for the rovibrational state ClO(v = 0 and j = 0) were obtained
      and are reported here. It was found that the OH product rotational polarization
      is not very sensitive to the collision energy selected. We discuss this
      phenomenon in detail. The calculated results indicate that, for this system, the
      two deep wells in the potential energy surface are very likely to be powerful
      influences on the degree of product rotational polarization. In addition, the
      microscopic reaction mechanism that dictates the product angular momentum
      orientation was investigated. The forward peak in the PDDCS00 at theta = 0
      degrees  in our study showed a strong dependence on the initial collision energy.

PMID- 24562861
TI  - A B3LYP and MP2(full) theoretical investigation on the cooperativity effect
      between hydrogen-bonding and cation-molecule interactions and thermodynamic
      property in the 1: 2 (Na+: N-(Hydroxymethyl)acetamide) ternary complex.
AB  - The cooperativity effects between the O/N-H???O hydrogen-bonding and Na+???O
      cation-molecule interactions in the 1: 2 (Na+: N-(Hydroxymethyl)acetamide)
      systems were investigated at the B3LYP/6-311++G**, MP2(full)/6-311++G** and
      MP2(full)/aug-cc-pvtz levels. The thermodynamic cooperativity calculations were
      also carried out for two pathways of the ternary-complex formation. The result
      shows that, in most ternary complexes, the O/N-H???O and Na+???O interactions are
      weakened in comparison with those in binary systems, leading to the anti
      cooperativity effects, in particular in the complexes in which only the Na+???O
      interactions exist. Shifts of electron density confirm the existence of anti
      cooperativity. The increase of favorable enthalpic contribution leads to the
      positive cooperativity effect with negative DeltaG(coop.) on forming the ternary
      complex by initial N-(Hydroxymethyl)acetamide dimer followed by addition of Na+.
      In forming the ternary complex by Na+???N-(Hydroxymethyl)acetamide with the
      second N-(Hydroxymethyl)acetamide unit, the large unfavorable entropy change
      leads to the negative cooperativity effect with positive DeltaG(coop.). The
      ternary complex is more easily formed by the pathway in which Na+ binds to N
      (Hydroxymethyl)acetamide dimer.

PMID- 24562864
TI  - Evidence for somatic transcription of male-transmitted mitochondrial genome in
      the DUI species Ruditapes philippinarum (Bivalvia: Veneridae).
AB  - In species with doubly uniparental inheritance (DUI), males are heteroplasmic for
      two sex-linked mitochondrial genomes (M- and F-mtDNA). While a role of M-mtDNA in
      male gametogenesis and sperm function is evident, there is an ongoing debate on
      whether it is transcribed or not in male soma. In this work we report a qPCR
      analysis in the DUI species Ruditapes philippinarum, showing that M-mtDNA is
      transcribed in somatic tissues. We observed a correlation between DNA copy
      numbers of the two analyzed genes, cytochrome b and a novel male-specific
      mitochondrial gene thought to be involved in DUI (orf21), and between their
      transcription levels. No correlation between a transcript and its DNA copy number
      was found, supporting the existence of complex regulatory mechanisms of
      mitochondrial transcription. We found the highest amount of mtDNA and mtRNA in
      gonads, likely due to the intense cell proliferation and high energy request for
      gametogenesis, while the observed variation among specimens is probably related
      to their different stages of gonad development. Finally, orf21 showed a highly
      variable transcription in advanced stages of gametogenesis. We hypothesize a
      differential storage of orf21 transcripts in spermatozoa, representing different
      paternal contributions to progeny, possibly leading to different developmental
      outcomes. A transcriptional activity does not necessarily imply the translation
      of M-mtDNA genes, and studies on mitochondrial proteins and their localization
      are needed to definitively assess the functioning of male-transmitted
      mitochondria in male soma. All that considered, the male soma of DUI species may
      represent an intriguing experimental model to study cytoplasmic genetic
      conflicts. 

PMID- 24562866
TI  - Preparation of Dufulin imprinted polymer on surface of silica gel and its
      application as solid-phase extraction sorbent.
AB  - A new molecularly imprinted polymer (MIP) based on silica-gel surface was
      developed using Dufulin (Duf) as a template, methacrylic acid (MAA) as a
      functional monomer, ethyleneglycol dimethacrylate (EGDMA) as a crosslinker, and
      azodiisobutyronitrile (AIBN) as an initiator. The synthetic samples were
      characterized by the techniques of Fourier transmission infrared spectrometry (FT
      IR) and scanning electron microscope (SEM). Batch experiments were performed to
      evaluate adsorption isotherms, adsorption kinetics and selective recognition of
      the MIP. Binding experiments demonstrated that the MIP had a good adsorption
      capacity, fast mass transfer rate and high recognition selectivity to Dufulin.
      When the MIP was used as a solid-phase extraction (SPE) material, the recoveries
      of Dufulin for spiked water, soil and wheat samples were 88.98-102.16%, 85.31
      99.57% and 87.84-100.19%, along with LOD of 0.0008 mg L(-1), 0.010 mg kg(-1) and
      0.023 mg kg(-1), respectively. Compared with direct determination of HPLC without
      MIP-SPE, the highly selective separation and enrichment of Dufulin from the
      complex environmental media can be achieved by the newly developed molecular
      imprinting at the surface of silica gel. 

PMID- 24562863
TI  - DNA mismatch repair MSH2 gene-based SNP associated with different populations.
AB  - We screened for the major essential single-nucleotide polymorphism (SNP) variant
      that might be associated with the MSH2 gene based on the data available from
      three types of human tissue samples [156 lymphoblastoid cell variations (LCL),
      160 epidermis, 166 fat]. An association analysis confirmed that the KCNK12 SNP
      variant (rs748780) was highly associated (p value 9 * 10(-4)) with the MSH2 gene
      for all three samples. Using SNP identification, we further found that the
      recognized SNP was also relevant among Hapmap populations. Techniques that
      display specific SNPs associated with the gene of interest or nearby genes
      provide more reliable genetic associations than techniques that rely on data from
      individual SNPs. We investigated the MSH2 gene regional linkage association with
      the determined SNP (rs748780), KCNK12 variant (Allele T>C) in the intronic
      region, in HapMap3 full dataset populations, Yoruba in Ibadan, Nigeria (YRI),
      Utah residents with ancestry from northern Europe (CEU), Han Chinese in Beijing,
      China (CHB), and a population of Mexican ancestry in Los Angeles, California
      (MEX). A gene-based SNP association analysis analyzes the combined impact of
      every variant within the gene while creating referrals to linkage disequilibrium
      or connections between markers. Our results indicated that among the four
      populations studied, this association was highest in the MEX population based on
      the r(2) value; a similar pattern was also observed in the other three
      populations. The relevant SNP rs748780 in KCNK12 is related to a superfamily of
      potassium channel pore-forming P-domain proteins as well as to other non-pore
      forming proteins and has been shown to be relevant to neurological disorder
      predisposition in MEX as well as in other populations.

PMID- 24562865
TI  - Selection and characterization of promoters based on genomic approach for the
      molecular breeding of oleaginous fungus Mortierella alpina 1S-4.
AB  - To express a foreign gene effectively, a good expression system is required. In
      this study, we investigated various promoters as useful tools for gene
      manipulation in oleaginous fungus Mortierella alpina 1S-4. We selected and cloned
      the promoter regions of 28 genes in M. alpina 1S-4 on the basis of expression
      sequence tag abundance data. The activity of each promoter was evaluated using
      the beta-glucuronidase (GUS) reporter gene. Eight of these promoters were shown
      to enhance GUS expression more efficiently than a histone promoter, which is
      conventionally used for the gene manipulation in M. alpina. Especially, the
      predicted protein 3 and the predicted protein 6 promoters demonstrated
      approximately fivefold higher activity than the histone promoter. The activity of
      some promoters changed along with the cultivation phase of M. alpina 1S-4. Seven
      promoters with constitutive or time-dependent, high-level expression activity
      were selected, and deletion analysis was carried out to determine the promoter
      regions required to retain activity. This is the first report of comprehensive
      promoter analysis based on a genomic approach for M. alpina. The promoters
      described here will be useful tools for gene manipulation in this strain. 

PMID- 24562868
TI  - Perlecan-enriched intercellular space of junctional epithelium provides primary
      infrastructure for leukocyte migration through squamous epithelial cells.
AB  - The aim of this study was to demonstrate the presence of intraepithelial stroma
      represented by extracellular matrix (ECM) deposits in the junctional epithelium
      to clarify its function as a scaffold for leukocyte migration through epithelial
      cells. Twenty-three biopsy specimens from the gingiva including the junctional
      epithelium were examined to determine comparative protein and gene level
      expression profiles for keratin and ECM molecules between the junctional
      epithelium and the gingival epithelium using immunohistochemistry and in situ
      hybridization. Intraepithelial leukocyte types and frequencies were also
      determined and compared between the junctional and gingival epithelia. In the
      junctional epithelium, which was positive for keratin 19, perlecan was strongly
      deposited in intercellular space of the whole epithelial layer, while it was
      faintly positive around the parabasal layer of the gingival epithelium. Perlecan
      mRNA signals were enhanced to a greater degree in both epithelial and
      inflammatory cells within the junctional epithelium. In the junctional
      epithelium, greater numbers of neutrophils and macrophages were found as compared
      with the gingival epithelium. Our results showed that perlecan is the primary ECM
      molecule comprising intraepithelial stroma of the junctional epithelium, in which
      leukocytes may migrate on ECM scaffolds in intercellular space toward the surface
      of the gingival sulci or pockets. 

PMID- 24562867
TI  - Motor function deficits in schizophrenia: an fMRI and VBM study.
AB  - INTRODUCTION: To investigate whether the motor functional alterations in
      schizophrenia (SZ) are also associated with structural changes in the related
      brain areas using functional magnetic resonance imaging (fMRI) and voxel-based
      morphometry (VBM). METHODS: A sample of 14 right-handed SZ patients and 14 right
      handed healthy control subjects matched for age, sex, and education were examined
      with structural high-resolution T1-weighted MRI; fMRI images were obtained during
      right index finger-tapping task in the same session. RESULTS: fMRI results showed
      reduced functional activation in the motor areas (contralateral precentral and
      postcentral gyrus) and ipsilateral cerebellum in SZ subjects as compared to
      healthy controls (n = 14). VBM analysis also revealed reduced grey matter in
      motor areas and white matter reduction in cerebellum of SZ subjects as compared
      to controls. CONCLUSION: The present study provides an evidence for a possible
      association between structural alterations in the motor cortex and disturbed
      functional activation in the motor areas in persons affected with SZ during a
      simple finger-tapping task.

PMID- 24562869
TI  - Establishment of in vitro culture system for evaluating dentin-pulp complex
      regeneration with special reference to the differentiation capacity of BrdU label
      retaining dental pulp cells.
AB  - We have proposed the new hypothesis that dental pulp stem cells play crucial
      roles in the pulpal healing process following exogenous stimuli in cooperation
      with progenitors. This study aimed to establish an in vitro culture system for
      evaluating dentin-pulp complex regeneration with special reference to the
      differentiation capacity of slow-cycling long-term label-retaining cells (LRCs).
      Three intraperitoneal injections of BrdU were given to pregnant ICR mice to map
      LRCs in the mature tissues of born animals. The upper bilateral first molars of 3
      week-old mice were extracted and divided into two pieces and cultured for 0, 1,
      3, 5 and 7 days using the Trowel's method. We succeeded in establishing an in
      vitro culture system for evaluating dentin-pulp complex regeneration, where most
      odontoblasts were occasionally degenerated and lost nestin immunoreactivity
      because of the separation of cell bodies from cellular processes in the dentin
      matrix by the beginning of in vitro culture. Numerous dense LRCs mainly resided
      in the center of the dental pulp associating with blood vessels throughout the
      experimental periods. On postoperative days 1-3, the periphery of the pulp tissue
      including the odontoblast layer showed degenerative features. By Day 7, nestin
      positive odontoblast-like cells were arranged along the pulp-dentin border and
      dense LRCs were committed in the odontoblast-like cells. These results suggest
      that dense LRCs in the center of the dental pulp associating with blood vessels
      were supposed to be dental pulp stem/progenitor cells possessing regenerative
      capacity for forming newly differentiated odontoblast-like cells.

PMID- 24562870
TI  - ROCK inhibition prevents early mouse embryo development.
AB  - ROCK is a Rho-GTPase effector that is important for actin assembly and is
      involved in various cellular functions, including cell contraction, migration,
      motility, and tumor cell invasion. In this study, we investigated ROCK expression
      and function during early mouse embryo development. Inhibiting ROCK by Y-27632
      treatment at the zygote stage resulted in first cleavage failure, and most
      embryos failed to develop to the 8-cell stage. When adding Y-27632 at the 8-cell
      stage, embryos failed to undergo compaction and could not develop into
      blastocysts. In addition, fluorescence staining intensity analysis indicated that
      actin expression at blastomere membranes was significantly reduced. After ROCK
      inhibition, two or more nuclei were observed in a cell, which indicated possible
      cytokinesis failure. Moreover, after ROCK inhibition with Y-27632, the
      phosphorylation levels of LIMK1/2, a downstream molecule of ROCK, were decreased
      at blastomere membranes. Thus, our results showed conserved roles for ROCK in
      this mammalian embryo model and indicated that a ROCK-LIMK1/2-actin pathway might
      regulate cleavage and blastocyst formation during early mouse embryo development.

PMID- 24562871
TI  - Ray tracing software for intraocular lens power calculation after corneal excimer
      laser surgery.
AB  - PURPOSE: To evaluate the accuracy of intraocular lens (IOL) power calculations
      using ray tracing software in eyes after myopic laser in situ keratomileusis
      (LASIK). METHODS: Twenty-four eyes of 17 cataract patients who underwent
      phacoemulsification and IOL implantation after myopic LASIK were analyzed
      retrospectively. The IOL power calculation was performed using OKULIX ray tracing
      software. The axial length was measured using the IOLMaster and keratometry data
      using TMS2N. The accuracy of the IOL power calculation using OKULIX was compared
      with those using the Camellin-Calossi, Shammas-PL, Haigis-L formulas and the
      double-K SRK/T formula using 43.5 diopters (D) for the Kpre. RESULTS: The mean
      values of the arithmetic and absolute prediction errors were 0.63 +/- 0.85 and
      0.80 +/- 0.68 D, respectively. The arithmetic prediction error by OKULIX was a
      significant hyperopic shift of the distribution of the postoperative refractive
      errors compared to the Camellin-Calossi, Shammas-PL and Haigis-L formulas (P <
      0.05), and the absolute prediction error showed no significant difference with
      other formulas. The prediction errors using OKULIX were within +/- 0.5 D in 10
      eyes (41.7 %) and within +/- 1.0 D in 18 eyes (75.0 %). The percentages of eyes
      within +/- 1.0 D using OKULIX were comparable to those obtained using the
      Camellin-Calossi, the Shammas-PL formulas and the double-K SRK/T formula using
      43.5 D for the Kpre, and significantly (P < 0.05) higher than that obtained using
      the Haigis-L formula. CONCLUSIONS: IOL power calculations using OKULIX provided
      predictable outcomes in eyes that had undergone a previous myopic LASIK.

PMID- 24562872
TI  - An assessment of computational methods for estimating purity and clonality using
      genomic data derived from heterogeneous tumor tissue samples.
AB  - Solid tumor samples typically contain multiple distinct clonal populations of
      cancer cells, and also stromal and immune cell contamination. A majority of the
      cancer genomics and transcriptomics studies do not explicitly consider genetic
      heterogeneity and impurity, and draw inferences based on mixed populations of
      cells. Deconvolution of genomic data from heterogeneous samples provides a
      powerful tool to address this limitation. We discuss several computational tools,
      which enable deconvolution of genomic and transcriptomic data from heterogeneous
      samples. We also performed a systematic comparative assessment of these tools. If
      properly used, these tools have potentials to complement single-cell genomics and
      immunoFISH analyses, and provide novel insights into tumor heterogeneity. 

PMID- 24562874
TI  - Is surgery for brachial plexus schwannomas safe and effective?
AB  - BACKGROUND: Schwannomas rarely are found in the brachial plexus, and although
      they are benign, they present significant challenges to surgical treatment. To
      our knowledge, there are few studies investigating the surgical outcomes of
      patients with brachial plexus tumors. QUESTIONS/PURPOSES: We analyzed the
      outcomes of 19 patients with brachial plexus schwannomas and asked: (1) How do
      these patients present? (2) Where are the tumors located in the brachial plexus?
      (3) What are the complications and neurologic results of patients after excision
      of the tumor? METHODS: From February 2002 to August 2012, one orthopaedic hand
      surgeon treated 19 patients with schwannomas of the brachial plexus. We
      retrospectively reviewed the medical records and MRI data of all patients. There
      were 11 women and eight men, with a mean age of 50.2 years (range, 32-63 years).
      The tumor was located on the right side in eight patients and on the left in 11
      patients. We evaluated neurologic deficits preoperatively and neurologic deficits
      and local recurrence of tumors postoperatively. Minimum followup was 12 months
      (mean, 37.2 months; range, 12-90 months). RESULTS: The most common initial
      presentation was a palpable mass. The masses were located at all levels along the
      brachial plexus, including the root, trunk, cord, and terminal branches. The
      smallest mass was 1.5 * 1.5 * 0.5 cm and the largest was 11 * 10 * 6 cm. Fourteen
      of the 19 patients did not have any postoperative neurologic deficits. All the
      removed masses were proven histologically to be schwannomas. Of the five patients
      who had postoperative neurologic deficits, three had transient sensory deficits,
      one had weakness of the flexor pollicis longus and second flexor digitorum
      profundus, and another had weakness of the extensor pollicis longus. No
      recurrence was observed during the followup period. CONCLUSIONS: Schwannomas of
      the brachial plexus are a potentially curable lesion with an acceptable surgical
      risk of injury to neurovascular structures. With precise surgical techniques,
      these tumors can be removed to improve symptoms with minimal morbidity. LEVEL OF
      EVIDENCE: Level IV, therapeutic study. See the Instructions for Authors for a
      complete description of levels of evidence.

PMID- 24562873
TI  - Are patients satisfied with a web-based followup after total joint arthroplasty?
AB  - BACKGROUND: A web-based followup assessment may be a feasible, cost-saving
      alternative of tracking patient outcomes after total joint arthroplasty. However,
      before implementing a web-based program, it is important to determine patient
      satisfaction levels with the new followup method. Satisfaction with the care
      received is becoming an increasingly important metric, and we do not know to what
      degree patients are satisfied with an approach to followup that does not involve
      an in-person visit with their surgeons. QUESTIONS/PURPOSES: We determined (1)
      patient satisfaction and (2) patients' preferences for followup method (web-based
      or in-person) after total joint arthroplasty. METHODS: We randomized patients who
      were at least 12 months after primary THA or TKA to complete a web-based followup
      or to have their appointment at the clinic. There were 410 eligible patients
      contacted for the study during the recruitment period. Of these, 256 agreed to
      participate, and a total of 229 patients completed the study (89% of those
      enrolled, 56% of those potentially eligible; 111 in the usual-care group, 118 in
      the web-based group). Their mean age was 69 years (range, 38-86 years). There was
      no crossover between groups. All 229 patients completed a satisfaction
      questionnaire at the time of their followup appointments. Patients in the web
      based group also completed a satisfaction and preference questionnaire 1 year
      later. Only patients from the web-based group were asked to indicate preference
      as they had experienced the web-based and in-person followup methods. We used
      descriptive statistics to summarize the satisfaction questionnaires and compared
      results using Pearson's chi-square test. RESULTS: Ninety-one patients (82.0%) in
      the usual-care group indicated that they were either extremely or very satisfied
      with the followup process compared with 90 patients (75.6%) who were in the web
      based group (p < 0.01; odds ratio [OR] = 3.95; 95% CI, 1.79-8.76). Similarly,
      patients in the usual care group were more satisfied with the care they received
      from their surgeon, compared with patients in the web-based group (92.8% versus
      73.9%; p < 0.01, OR = 1.37; 95% CI, 0.73-2.57). Forty-four percent of patients
      preferred the web-based method, 36% preferred the usual method, and 16% had no
      preference (p = 0.01). CONCLUSIONS: Our results show moderate to high
      satisfaction levels with a web-based followup assessment. Patients who completed
      the usual method of in-person followup assessment reported greater satisfaction;
      however, the difference was small and may not outweigh the additional cost and
      time-saving benefits of the web-based followup method. LEVEL OF EVIDENCE: Level
      I, therapeutic study. See the Instructions for Authors for a complete description
      of levels of evidence.

PMID- 24562875
TI  - Targeted muscle reinnervation: a novel approach to postamputation neuroma pain.
AB  - BACKGROUND: Postamputation neuroma pain can prevent comfortable prosthesis wear
      in patients with limb amputations, and currently available treatments are not
      consistently effective. Targeted muscle reinnervation (TMR) is a decade-old
      technique that employs a series of novel nerve transfers to permit intuitive
      control of upper-limb prostheses. Clinical experience suggests that it may also
      serve as an effective therapy for postamputation neuroma pain; however, this has
      not been explicitly studied. QUESTIONS/PURPOSES: We evaluated the effect of TMR
      on residual limb neuroma pain in upper-extremity amputees. METHODS: We conducted
      a retrospective medical record review of all 28 patients treated with TMR from
      2002 to 2012 at Northwestern Memorial Hospital/Rehabilitation Institute of
      Chicago (Chicago, IL, USA) and San Antonio Military Medical Center (San Antonio,
      TX, USA). Twenty-six of 28 patients had sufficient (> 6 months) followup for
      study inclusion. The amputation levels were shoulder disarticulation (10
      patients) and transhumeral (16 patients). All patients underwent TMR for the
      primary purpose of improved myoelectric control. Of the 26 patients included in
      the study, 15 patients had evidence of postamputation neuroma pain before
      undergoing TMR. RESULTS: Of the 15 patients presenting with neuroma pain before
      TMR, 14 experienced complete resolution of pain in the transferred nerves, and
      the remaining patient's pain improved (though did not resolve). None of the
      patients who presented without evidence of postamputation neuroma pain developed
      neuroma pain after the TMR procedure. All 26 patients were fitted with a
      prosthesis, and 23 of the 26 patients were able to operate a TMR-controlled
      prosthesis. CONCLUSIONS: None of the 26 patients who underwent TMR demonstrated
      evidence of new neuroma pain after the procedure, and all but one of the 15
      patients who presented with preoperative neuroma pain experienced complete relief
      of pain in the distribution of the transferred nerves. TMR offers a novel and
      potentially more effective therapy for the management of neuroma pain after limb
      amputation.

PMID- 24562878
TI  - Effects of vitamin C on the hypobaric hypoxia-induced immune changes in male
      rats.
AB  - Hypobaric hypoxia (HH) induces oxidative stress (OS) and is associated with the
      generation of reactive oxygen species (ROS). Vitamin C is an efficient
      antioxidant, and it is used in a high-altitude environment to reduce the OS. The
      present study explores the role of vitamin C on some HH-induced changes of immune
      parameters in rats which were exposed to HHc condition at 18,000 ft in a
      simulated chamber for 8 h/day for 6 days with and without vitamin C
      administration at three different doses (200, 400, and 600 mg/kg body wt). The
      phagocytic activity of circulating blood WBC was increased, and the cytotoxic
      activity of splenic mononuclear cell (MNC) and the delayed type of
      hypersensitivity (DTH) responses to bovine serum albumin (BSA) were decreased in
      rats exposed to HHc condition, but these immune changes were blocked after
      administration of vitamin C at 400 mg/kg body wt. The leukocyte adhesive
      inhibition index (LAI) was not altered either in HHc condition or after
      administration of vitamin C in HHc condition. The serum corticosterone (CORT)
      concentration was increased in rats exposed to HHc condition which was blocked
      after administration of vitamin C (400 mg/kg body wt). The immune parameters and
      serum CORT concentration, however, did not show any recovery after administration
      of vitamin C at the dose of 200 and 600 mg/kg body wt. The present study
      indicates that administration of vitamin C at a dose of 400 mg/kg body wt may
      prevent the HH-induced immunological changes but not at the lower dose (200 mg/kg
      body wt) or higher dose (600 mg/kg body wt) in rats.

PMID- 24562899
TI  - Vascular risk factors aggravate the progression of Alzheimer's disease: a 3-year
      follow-up study of Chinese population.
AB  - PURPOSE: To explore the correlation of vascular risk factors for Alzheimer's
      disease (AD) in Chinese population. METHODS: A total of 123 outpatients with
      probable AD followed up for 3 years were investigated. Severity of cognitive
      impairment and functional ability was assessed using Mini-Mental State
      Examination (MMSE) and modified activities of daily living (ADLs), respectively.
      The incidence of vascular risk factors was studied in patients with AD. RESULTS:
      Univariate analysis showed significance difference in MMSE and ADL scores between
      patients with and without vascular risk factors (P < .05). Multiple regression
      analysis showed age, education, hyperhomocysteinemia, and hypertension were
      significant variables associated with annual MMSE, while there were no
      significant correlations between annual MMSE and sex, initial MMSE, diabetes, and
      so on. CONCLUSIONS: Vascular risk factors are common comorbidities in patients
      with AD in China, with younger, better educated ones showing faster cognitive
      decline. Hypertension and hyperhomocysteinemia may also aggravate the
      progression, and it is important to prevent and treat patients with AD.

PMID- 24562889
TI  - Import of desired nucleic acid sequences using addressing motif of mitochondrial
      ribosomal 5S-rRNA for fluorescent in vivo hybridization of mitochondrial DNA and
      RNA.
AB  - Based on the matrix-addressing sequence of mitochondrial ribosomal 5S-rRNA
      (termed MAM), which is naturally imported into mitochondria, we have constructed
      an import system for in vivo targeting of mitochondrial DNA (mtDNA) or mt-mRNA,
      in order to provide fluorescence hybridization of the desired sequences. Thus DNA
      oligonucleotides were constructed, containing the 5'-flanked T7 RNA polymerase
      promoter. After in vitro transcription and fluorescent labeling with Alexa
      Fluor((r)) 488 or 647 dye, we obtained the fluorescent "L-ND5 probe" containing
      MAM and exemplar cargo, i.e., annealing sequence to a short portion of ND5 mRNA
      and to the light-strand mtDNA complementary to the heavy strand nd5 mt gene (5'
      end 21 base pair sequence). For mitochondrial in vivo fluorescent hybridization,
      HepG2 cells were treated with dequalinium micelles, containing the fluorescent
      probes, bringing the probes proximally to the mitochondrial outer membrane and to
      the natural import system. A verification of import into the mitochondrial matrix
      of cultured HepG2 cells was provided by confocal microscopy colocalizations.
      Transfections using lipofectamine or probes without 5S-rRNA addressing MAM
      sequence or with MAM only were ineffective. Alternatively, the same DNA
      oligonucleotides with 5'-CACC overhang (substituting T7 promoter) were
      transcribed from the tetracycline-inducible pENTRH1/TO vector in human embryonic
      kidney T-REx(r)-293 cells, while mitochondrial matrix localization after import
      of the resulting unlabeled RNA was detected by PCR. The MAM-containing probe was
      then enriched by three-order of magnitude over the natural ND5 mRNA in the
      mitochondrial matrix. In conclusion, we present a proof-of-principle for
      mitochondrial in vivo hybridization and mitochondrial nucleic acid import. 

PMID- 24562905
TI  - Anti-Mullerian hormone and risk of invasive serous ovarian cancer.
AB  - PURPOSE: Epithelial ovarian cancers either arise directly from Mullerian-type
      epithelium or acquire Mullerian characteristics in the course of neoplastic
      transformation. The anti-Mullerian hormone (AMH) causes regression of Mullerian
      structures during fetal development in males and has been shown to inhibit the
      growth of epithelial ovarian cancer. Therefore, we hypothesized that pre
      diagnostic serum concentrations of AMH are inversely associated with risk of
      invasive serous ovarian cancer. METHODS: A case-control study (107 cases, 208
      controls) was nested within the population-based Finnish Maternity Cohort (1986
      2007). The sample donated during the first trimester of the last pregnancy
      preceding cancer diagnosis of the case subjects was selected for the study. For
      each case, two controls, matched on age and date at sampling, as well as parity
      at sampling and at cancer diagnosis were selected. AMH was measured by a second
      generation AMH ELISA. Conditional logistic regression was used to compute odds
      ratios (OR) and 95 % confidence intervals (CI) for invasive serous ovarian cancer
      associated with AMH concentrations. RESULTS: Overall AMH concentrations were not
      associated with risk of invasive serous ovarian cancer (OR 0.93; 95 % CI 0.49
      1.77 for top vs. bottom tertile, P trend=0.83). In women older than the median
      age at sampling (32.7 years), a doubling of AMH was associated with decreased
      risk (OR 0.69; 95 % CI 0.49-0.96), whereas an increased risk (OR 1.64; 95 % CI
      1.06-2.54) was observed in younger women, P homogeneity = 0.002. CONCLUSIONS: In
      this first prospective investigation, risk of invasive serous ovarian cancer was
      not associated with pre-diagnostic AMH concentrations overall; however, the
      association may depend on age at AMH measurement.

PMID- 24562904
TI  - Total calcium intake and colorectal adenoma in young women.
AB  - BACKGROUND: Total calcium intake appears to reduce occurrence of colorectal
      adenoma; however, the dose necessary for prevention in young women is unclear. We
      examined fine categories of calcium intake in relation to occurrence of first
      colorectal adenoma in a cohort of mostly premenopausal (88 %) women aged 26-60 at
      time of endoscopy. DESIGN: We conducted an analysis among 41,403 participants in
      the Nurses' Health Study II and assessed intakes of calcium prior to endoscopy
      through participants' responses to biannual questionnaires. RESULTS: Between 1991
      and 2007, we documented 2,273 colorectal adenoma cases. There was a significant
      trend across categories of calcium intakes with lowest intakes suggestive of
      higher occurrence of adenoma (p = 0.03) and those in the distal colon (p = 0.03)
      and rectum (p = 0.04). Compared with 1,001-1,250 mg/day of calcium intake, <= 500
      mg/day was suggestive of a modest increase in occurrence of adenoma
      (multivariable RR = 1.21, 95 % CI 0.90-1.61); there were also suggestions of an
      increased risk with >500 to <= 700 mg/day of calcium. The association between <=
      500 mg/day of calcium intake and adenoma was stronger for multiple (RR = 2.27, 95
      % CI 1.38, 3.72), large (>= 1 cm) (RR = 2.01, 95 % CI 1.27, 3.21), and high-risk
      adenoma (>= 1 cm or mention of villous histology/high-grade dysplasia) (RR =
      1.76, 95 % CI 1.13, 2.72). No differences in associations were noted between
      jointly categorized calcium and phosphorus or magnesium intakes. CONCLUSIONS: Our
      findings suggest that low intakes of calcium, <500 and possibly 500-700 mg/day,
      in younger women are associated with an increased risk of multiple and advanced
      colorectal adenoma.

PMID- 24562906
TI  - [Oral anticoagulation for atrial fibrillation].
AB  - The correct oral anticoagulation for prevention of thromboembolic events in
      patients with atrial fibrillation and a corresponding risk profile is essential.
      However, anticoagulation is not carried out according to the guidelines in all
      patients. The direct oral anticoagulants (DOACs) are a new treatment alternative
      to vitamin K antagonists. The new guidelines of the European Society of
      Cardiology (ESC), recent study results and the practice guidelines of the
      European Heart Rhythm Association (EHRA) can help to use DOACs appropriately, to
      optimize the prevention of thromboembolic events in patients with atrial
      fibrillation and to reduce complications. 

PMID- 24562907
TI  - Genetic validation of aminoacyl-tRNA synthetases as drug targets in Trypanosoma
      brucei.
AB  - Human African trypanosomiasis (HAT) is an important public health threat in sub
      Saharan Africa. Current drugs are unsatisfactory, and new drugs are being sought.
      Few validated enzyme targets are available to support drug discovery efforts, so
      our goal was to obtain essentiality data on genes with proven utility as drug
      targets. Aminoacyl-tRNA synthetases (aaRSs) are known drug targets for bacterial
      and fungal pathogens and are required for protein synthesis. Here we survey the
      essentiality of eight Trypanosoma brucei aaRSs by RNA interference (RNAi) gene
      expression knockdown, covering an enzyme from each major aaRS class: valyl-tRNA
      synthetase (ValRS) (class Ia), tryptophanyl-tRNA synthetase (TrpRS-1) (class Ib),
      arginyl-tRNA synthetase (ArgRS) (class Ic), glutamyl-tRNA synthetase (GluRS)
      (class 1c), threonyl-tRNA synthetase (ThrRS) (class IIa), asparaginyl-tRNA
      synthetase (AsnRS) (class IIb), and phenylalanyl-tRNA synthetase (alpha and beta)
      (PheRS) (class IIc). Knockdown of mRNA encoding these enzymes in T. brucei
      mammalian stage parasites showed that all were essential for parasite growth and
      survival in vitro. The reduced expression resulted in growth, morphological, cell
      cycle, and DNA content abnormalities. ThrRS was characterized in greater detail,
      showing that the purified recombinant enzyme displayed ThrRS activity and that
      the protein localized to both the cytosol and mitochondrion. Borrelidin, a known
      inhibitor of ThrRS, was an inhibitor of T. brucei ThrRS and showed
      antitrypanosomal activity. The data show that aaRSs are essential for T. brucei
      survival and are likely to be excellent targets for drug discovery efforts. 

PMID- 24562908
TI  - The Entamoeba histolytica Dnmt2 homolog (Ehmeth) confers resistance to
      nitrosative stress.
AB  - Nitric oxide (NO) has antimicrobial properties against many pathogens due to its
      reactivity as an S-nitrosylating agent. It inhibits many of the key enzymes that
      are involved in the metabolism and virulence of the parasite Entamoeba
      histolytica through S-nitrosylation of essential cysteine residues. Very little
      information is available on the mechanism of resistance to NO by pathogens in
      general and by this parasite in particular. Here, we report that exposure of the
      parasites to S-nitrosoglutathione (GSNO), an NO donor molecule, strongly reduces
      their viability and protein synthesis. However, the deleterious effects of NO
      were significantly reduced in trophozoites overexpressing Ehmeth, the cytosine-5
      methyltransferase of the Dnmt2 family. Since these trophozoites also exhibited
      high levels of tRNA(Asp) methylation, the high levels suggested that Ehmeth
      mediated tRNA(Asp) methylation is part of the resistance mechanism to NO. We
      previously reported that enolase, another glycolytic enzyme, binds to Ehmeth and
      inhibits its activity. We observed that the amount of Ehmeth-enolase complex was
      significantly reduced in GSNO-treated E. histolytica, which explains the
      aforementioned increase of tRNA methylation. Specifically, we demonstrated via
      site-directed mutagenesis that cysteine residues 228 and 229 of Ehmeth are
      susceptible to S-nitrosylation and are crucial for Ehmeth binding to enolase and
      for Ehmeth-mediated resistance to NO. These results indicate that Ehmeth has a
      central role in the response of the parasite to NO, and they contribute to the
      growing evidence that NO is a regulator of epigenetic mechanisms. 

PMID- 24562909
TI  - Dictyostelium discoideum Dgat2 can substitute for the essential function of Dgat1
      in triglyceride production but not in ether lipid synthesis.
AB  - Triacylglycerol (TAG), the common energy storage molecule, is formed from
      diacylglycerol and a coenzyme A-activated fatty acid by the action of an acyl
      coenzyme A:diacylglycerol acyltransferase (DGAT). In order to conduct this step,
      most organisms rely on more than one enzyme. The two main candidates in
      Dictyostelium discoideum are Dgat1 and Dgat2. We show, by creating single and
      double knockout mutants, that the endoplasmic reticulum (ER)-localized Dgat1
      enzyme provides the predominant activity, whereas the lipid droplet constituent
      Dgat2 contributes less activity. This situation may be opposite from what is seen
      in mammalian cells. Dictyostelium Dgat2 is specialized for the synthesis of TAG,
      as is the mammalian enzyme. In contrast, mammalian DGAT1 is more promiscuous
      regarding its substrates, producing diacylglycerol, retinyl esters, and waxes in
      addition to TAG. The Dictyostelium Dgat1, however, produces TAG, wax esters, and,
      most interestingly, also neutral ether lipids, which represent a significant
      constituent of lipid droplets. Ether lipids had also been found in mammalian
      lipid droplets, but the role of DGAT1 in their synthesis was unknown. The ability
      to form TAG through either Dgat1 or Dgat2 activity is essential for Dictyostelium
      to grow on bacteria, its natural food substrate. 

PMID- 24562910
TI  - Trypanosome alternative oxidase possesses both an N-terminal and internal
      mitochondrial targeting signal.
AB  - Recognition of mitochondrial targeting signals (MTS) by receptor translocases of
      outer and inner membranes of mitochondria is one of the prerequisites for import
      of nucleus-encoded proteins into this organelle. The MTS for a majority of
      trypanosomatid mitochondrial proteins have not been well defined. Here we
      analyzed the targeting signal for trypanosome alternative oxidase (TAO), which
      functions as the sole terminal oxidase in the infective form of Trypanosoma
      brucei. Deleting the first 10 of 24 amino acids predicted to be the classical N
      terminal MTS of TAO did not affect its import into mitochondria in vitro.
      Furthermore, ectopically expressed TAO was targeted to mitochondria in both forms
      of the parasite even after deletion of first 40 amino acid residues. However,
      deletion of more than 20 amino acid residues from the N terminus reduced the
      efficiency of import. These data suggest that besides an N-terminal MTS, TAO
      possesses an internal mitochondrial targeting signal. In addition, both the N
      terminal MTS and the mature TAO protein were able to target a cytosolic protein,
      dihydrofolate reductase (DHFR), to a T. brucei mitochondrion. Further analysis
      identified a cryptic internal MTS of TAO, located within amino acid residues 115
      to 146, which was fully capable of targeting DHFR to mitochondria. The internal
      signal was more efficient than the N-terminal MTS for import of this heterologous
      protein. Together, these results show that TAO possesses a cleavable N-terminal
      MTS as well as an internal MTS and that these signals act together for efficient
      import of TAO into mitochondria. 

PMID- 24562913
TI  - FDG-PET/CT assessment of differential chemotherapy effects upon skeletal muscle
      metabolism in patients with melanoma.
AB  - OBJECTIVES: To quantify the differential effects of chemotherapy on the metabolic
      activity of skeletal muscle in vivo using molecular imaging with [18F]
      fluorodeoxyglucose (FDG)-positron emission tomography/computed tomography
      (PET/CT). METHODS: In this retrospective study, 21 subjects with stage IV
      melanoma who underwent pre- and post-chemotherapy whole-body FDG-PET/CT imaging
      were included. The mean standardized uptake value (SUVmean) of 8 different
      skeletal muscles was measured per subject. Pre- and post-treatment measurements
      were then averaged across all subjects for each muscle and compared for
      statistically significant differences between the muscles and following different
      chemotherapy regimens including dacarbazine (DTIC) and temozolomide (TMZ).
      RESULTS: Analysis of FDG-PET/CT images reliably detected changes in skeletal
      muscle metabolic activity based on muscle location. The percent change in
      metabolic activity of each skeletal muscle in each subject following chemotherapy
      was observed to be related to the type of chemotherapy received. Subjects
      receiving DTIC generally had a decrease in metabolic activity of all muscle
      groups, whereas subjects receiving TMZ generally had an increase in muscle
      activity of all muscle groups. CONCLUSION: FDG-PET/CT can reveal baseline
      metabolic differences between different muscles of the body. Different
      chemotherapies are associated with differential changes in the metabolic activity
      of skeletal muscle, which can be detected and quantified with FDG-PET/CT.

PMID- 24562912
TI  - Virtual screening of potential inhibitors from TCM for the CPSF30 binding site on
      the NS1A protein of influenza A virus.
AB  - Inhibition of CPSF30 function by the effector domain of influenza A virus of non
      structural protein 1 (NS1A) protein plays a critical role in the suppression of
      host key antiviral response. The CPSF30-binding site of NS1A appears to be a very
      attractive target for the development of new drugs against influenza A virus. In
      this study, structure-based molecular docking was utilized to screen more than
      30,000 compounds from a Traditional Chinese Medicine (TCM) database. Four drug
      like compounds were selected as potential inhibitors for the CPSF30-binding site
      of NS1A. Docking conformation analysis results showed that these potential
      inhibitors could bind to the CPSF30-binding site with strong hydrophobic
      interactions and weak hydrogen bonds. Molecular dynamics simulations and MM-PBSA
      calculations suggested that two of the inhibitors, compounds 32056 and 31674,
      could stably bind to the CPSF30-binding site with high binding free energy. These
      two compounds could be modified to achieve higher binding affinity, so that they
      may be used as potential leads in the development of new anti-influenza drugs. 

PMID- 24562911
TI  - Multiple nuclear localization signals mediate nuclear localization of the GATA
      transcription factor AreA.
AB  - The Aspergillus nidulans GATA transcription factor AreA activates transcription
      of nitrogen metabolic genes in response to nitrogen limitation and is known to
      accumulate in the nucleus during nitrogen starvation. Sequence analysis of AreA
      revealed multiple nuclear localization signals (NLSs), five putative classical
      NLSs conserved in fungal AreA orthologs but not in the Saccharomyces cerevisiae
      functional orthologs Gln3p and Gat1p, and one putative noncanonical RRX33RXR
      bipartite NLS within the DNA-binding domain. In order to identify the functional
      NLSs in AreA, we constructed areA mutants with mutations in individual putative
      NLSs or combinations of putative NLSs and strains expressing green fluorescent
      protein (GFP)-AreA NLS fusion genes. Deletion of all five classical NLSs
      individually or collectively did not affect utilization of nitrogen sources or
      AreA-dependent gene expression and did not prevent AreA nuclear localization.
      Mutation of the bipartite NLS conferred the inability to utilize alternative
      nitrogen sources and abolished AreA-dependent gene expression likely due to
      effects on DNA binding but did not prevent AreA nuclear localization. Mutation of
      all six NLSs simultaneously prevented AreA nuclear accumulation. The bipartite
      NLS alone strongly directed GFP to the nucleus, whereas the classical NLSs
      collaborated to direct GFP to the nucleus. Therefore, AreA contains multiple
      conserved NLSs, which show redundancy and together function to mediate nuclear
      import. The noncanonical bipartite NLS is conserved in GATA factors from
      Aspergillus, yeast, and mammals, indicating an ancient origin. 

PMID- 24562915
TI  - Predicting the ancestral character changes in a tree is typically easier than
      predicting the root state.
AB  - Predicting the ancestral sequences of a group of homologous sequences related by
      a phylogenetic tree has been the subject of many studies, and numerous methods
      have been proposed for this purpose. Theoretical results are available that show
      that when the substitution rates become too large, reconstructing the ancestral
      state at the tree root is no longer feasible. Here, we also study the
      reconstruction of the ancestral changes that occurred along the tree edges. We
      show that, that, depending on the tree and branch length distribution,
      reconstructing these changes (i.e., reconstructing the ancestral state of all
      internal nodes in the tree) may be easier or harder than reconstructing the
      ancestral root state. However, results from information theory indicate that for
      the standard Yule tree, the task of reconstructing internal node states remains
      feasible, even for very high substitution rates. Moreover, computer simulations
      demonstrate that for more complex trees and scenarios, this result still holds.
      For a large variety of counting, parsimony- and likelihood-based methods, the
      predictive accuracy of a randomly selected internal node in the tree is indeed
      much higher than the accuracy of the same method when applied to the tree root.
      Moreover, parsimony- and likelihood-based methods appear to be remarkably robust
      to sampling bias and model mis-specification.

PMID- 24562914
TI  - How co-morbidities magnify the effect of arthritis on labour force participation
      and economic status: a costs of illness study in Australia.
AB  - Few studies have assessed the impact of co-morbid conditions amongst patients
      with arthritis. This study will quantify the impact co-morbid health conditions
      have on the labour force status and economic circumstances of people with
      arthritis. This study uses a microsimulation model, Health&WealthMOD, to quantify
      the impact of co-morbidities on the labour force participation and economic
      circumstances of 45- to 64-year-old Australians with arthritis. The results show
      that the probability of being out of the labour force increases with increasing
      number of co-morbidities. However, there was no statistically significant
      difference in the amount of weekly private income received by people with
      arthritis and no co-morbidities, and people with arthritis and one or two co
      morbidities. However, those with arthritis and three or more co-morbidities
      received a weekly private income 72 % lower than people with arthritis alone (95
      % CI -82, -57). People with arthritis and co-morbidities paid less in tax and
      received more in government transfer payments. As such, it is important to
      consider the co-morbid conditions an individual has when assessing the impact of
      arthritis on labour force participation and economic circumstances. People with
      arthritis that have multiple co-morbid conditions are likely to have their labour
      force participation and economic circumstances interrupted much more than those
      with arthritis only.

PMID- 24562916
TI  - Predictive approaches to assessing the fit of evolutionary models.

PMID- 24562931
TI  - Liver transplantation for unresectable neuroendocrine tumor liver metastases.
AB  - BACKGROUND: Liver transplantation (LT) is performed in selected patients with
      neuroendocrine hepatic metastases. Survival benefit and the risk of tumor
      recurrence after LT, also exacerbated by immunosuppressive therapy, remain
      important clinical issues. Whether patients with particular types of
      neuroendocrine tumors (NET) benefit more than others is unclear. METHODS:
      Bibliographical searches were performed in PubMed for the terms "liver
      transplantation and neuroendocrine tumors," "liver transplant and neuroendocrine
      tumors," "liver transplantation and immunosuppressive therapy," "tumor
      recurrence." RESULTS: Promising results have been reported for LT for NET
      metastases with 5-year survival of up to 90 % in patients with well
      differentiated gastroenteropancreatic NETs, but only few patients are free of
      tumor 5 years after LT. Better outcomes have been reported for gastrointestinal
      tumors than for pancreatic NETs for both survival and risk or recurrence after
      LT. Selection criteria for LT are limited and include the 2007 Milan Criteria and
      the 2012 European Neuroendocrine Tumor Society guidelines, including: well
      differentiated NET (Ki-67 <10 %), age <55 years, absence of extrahepatic disease,
      primary tumor removed before transplantation, stable disease for at least 6
      months before LT, and <50 % liver involvement. CONCLUSIONS: LT might be
      considered in carefully selected patients. The risk of tumor recurrence remains a
      significant clinical problem after LT, but data focused on immunosuppression
      issue are lacking, and there are no currently approved strategies for prevention
      of recurrence or follow-up protocols. Further studies are needed to define
      universally accepted inclusion criteria, reliable predictors of better outcome,
      and optimal timing for LT.

PMID- 24562917
TI  - Auxin overproduction in shoots cannot rescue auxin deficiencies in Arabidopsis
      roots.
AB  - Auxin plays an essential role in root development. It has been a long-held dogma
      that auxin required for root development is mainly transported from shoots into
      roots by polarly localized auxin transporters. However, it is known that auxin is
      also synthesized in roots. Here we demonstrate that a group of YUCCA (YUC) genes,
      which encode the rate-limiting enzymes for auxin biosynthesis, plays an essential
      role in Arabidopsis root development. Five YUC genes (YUC3, YUC5, YUC7, YUC8 and
      YUC9) display distinct expression patterns during root development. Simultaneous
      inactivation of the five YUC genes (yucQ mutants) leads to the development of
      very short and agravitropic primary roots. The yucQ phenotypes are rescued by
      either adding 5 nM of the natural auxin, IAA, in the growth media or by
      expressing a YUC gene in the roots of yucQ. Interestingly, overexpression of a
      YUC gene in shoots in yucQ causes the characteristic auxin overproduction
      phenotypes in shoots; however, the root defects of yucQ are not rescued. Our data
      demonstrate that localized auxin biosynthesis in roots is required for normal
      root development and that auxin transported from shoots is not sufficient for
      supporting root elongation and root gravitropic responses. 

PMID- 24562930
TI  - Basal subtype, as approximated by triple-negative phenotype, is associated with
      locoregional recurrence in a case-control study of women with 0-3 positive lymph
      nodes after mastectomy.
AB  - PURPOSE: Basal subtype, as approximated by the triple-negative phenotype (ER-PR
      Her2-), has correlated with higher LRR in recent studies. Indications for
      postmastectomy RT (PMRT) in women with 0-3 positive lymph nodes remain unclear.
      We evaluated the importance of biologic subtype in a cohort of women with LRR
      after mastectomy. METHODS: We identified 22 women with 0-3 positive lymph nodes
      at our institution who were initially treated with mastectomy (without post
      mastectomy radiation), suffered LRRs, and had paraffin-embedded tissue blocks
      from the primary mastectomy specimen available for staining. None of these women
      received PMRT. We case-control matched these to 29 women with 0-3 positive nodes
      who had mastectomy (no PMRT) and remained without evidence of disease at last
      follow-up and had available primary specimens for processing. We matched controls
      for age (+/-3 years) and follow-up duration (<5 year vs. more). Paraffin-embedded
      specimens were used to construct a triple-redundant tissue microarray. We used
      conditional logistic regressions to study the association between each predictor
      and LRR. Results were summarized based on odds ratio (OR). RESULTS: On univariate
      analysis, ER+, PR+, or the combination was strongly associated with lower odds of
      LRR. Basal subtype, as approximated by ER-PR-Her2- (TN), was associated with
      higher LRR (OR 8.5, p = 0.048). Use of chemotherapy also was associated with
      lower LRR (OR 0.126, p = 0.0073). CONCLUSIONS: Our data are concordant with
      reports from others demonstrating that TN phenotype is associated with higher LRR
      and can be considered along with other predictors of LRR when selecting women for
      PMRT.

PMID- 24562932
TI  - Combined morphologic and molecular classification for predicting lymph node
      metastasis in early-stage colorectal adenocarcinoma.
AB  - BACKGROUND: Identifying reliable predictors of lymph node (LN) metastasis is
      clinically important, particularly for optimizing treatments for early colorectal
      cancer (ECC) patients. This study evaluated risk-predictive models of LN
      metastasis using several pathologic and molecular ECC parameters. METHODS: Tissue
      specimens from 179 patients with histologically confirmed ECC were enrolled. A
      total of 20 clinicopathological characteristics, including tumor budding,
      micropapillary structure, and mucinous differentiation, and 22 protein
      expressions related to cancer invasion in central and invasive front areas were
      evaluated for their predictive value for LN metastasis. RESULTS: Alongside
      conventional histopathological parameters, tumor budding and mucinous
      differentiation at the invasive front of ECCs and micropapillary structure were
      found to be independent predictive factors for LN metastasis. Immunohistochemical
      expressions of CXCL12 and p38-MAPK at the invasive front were also found to be
      associated with regional LN metastasis in ECC. Analytic logistic models, using
      combinations of statistically independent parameters, revealed their abilities to
      predict LN metastasis in ECC. Further, receiver operating characteristic analysis
      using combinations of 6 or 7 independent variables represented predictive
      performances (area under curve of 0.956 or 0.960, respectively) for LN metastasis
      in ECC. CONCLUSIONS: The combined histomorphologic and molecular factors tested
      here might be able to predict for LN metastasis in ECC.

PMID- 24562933
TI  - Biological differential diagnosis of follicular thyroid tumor and Hurthle cell
      tumor on the basis of telomere length and hTERT expression.
AB  - BACKGROUND: The most difficult thyroid tumors to diagnose by histology are
      follicular carcinomas (FTCs) and Hurthle cell carcinomas (HCCs). Telomere
      alteration and human telomerase reverse transcriptase (hTERT) expression have
      been observed in most human cancers and are known to be a feature of malignancy.
      The purpose of this study was to clarify whether hTERT protein expression and
      telomere alteration could be applicable biological markers for distinguishing FTC
      from HCC. METHODS: We investigated a total of 78 thyroid tumor cases, including
      14 FTCs, 47 follicular adenomas (FTAs), 5 HCCs, and 12 Hurthle cell adenomas
      (HCAs). hTERT protein expression was examined by immunohistochemistry, and
      telomere length was determined by tissue quantitative fluorescence in situ
      hybridization. RESULTS: Positivity for hTERT protein expression was observed in
      86 % of FTCs and 49 % of FTAs. Telomeres in FTCs were significantly shorter than
      those in FTAs. All HCCs and HCAs (100 %) expressed hTERT protein. Telomeres in
      HCCs were significantly shorter than those in HCAs. CONCLUSIONS: Our results
      suggest that hTERT protein expression and telomere shortening would be applicable
      as biological markers to distinguish FTC from FTA. Previous studies have
      suggested that follicular tumor and Hurthle cell tumor should be classified
      biologically as distinct tumors. All Hurthle cell tumors expressed hTERT protein
      and HCCs had markedly shortened telomeres, suggesting that follicular tumor and
      Hurthle cell tumor might be biologically distinct entities.

PMID- 24562934
TI  - Upregulation of HGF and c-MET is associated with subclinical central lymph node
      metastasis in papillary thyroid microcarcinoma.
AB  - BACKGROUND: Identification of a novel biomarker of subclinical lymph node
      metastasis (SLNM) in papillary thyroid microcarcinoma (PTMC) could provide
      important clues regarding SLNM in PTMC. We evaluated the significance of HGF and
      c-Met expression in surgically removed tumor tissue from PTMC patients as a
      predictive marker of SLNM. METHODS: We analyzed the immunohistochemical
      relationship between HGF and c-Met expression and SLNM in 113 surgically treated
      PTMC patients with clinically negative nodes presurgery. In addition, we explored
      whether HGF/c-Met pathway activation enhanced the in vitro migration and invasion
      of PTC cells. RESULTS: Positive immunohistochemical HGF and c-Met staining was
      found in 107 (95 %) and 103 (91 %) cases, respectively. The HGF staining
      distribution was as follows: no staining in 6 cases, weak staining in 43,
      moderate staining in 55, and strong staining in 9. Of the nine cases with strong
      HGF staining, eight (89 %) had SLNM. The c-Met staining distribution was as
      follows: no staining in 10 cases, weak staining in 39, moderate staining in 59,
      and strong staining in 5. Of the five cases with strong c-Met staining, three (60
      %) had SLNM. The presence of SLNM was strongly correlated with HGF and c-Met
      expression in PTMC in a univariate analysis (P < 0.05). HGF overexpression was
      also associated with SLNM in a multivariate analysis (P < 0.05). Stimulation with
      exogenous HGF and constitutive activation of c-Met enhanced the migration and
      invasion of PTC cells in vitro by enhancing VEGF-A expression. CONCLUSIONS: HGF/c
      Met pathway activation is associated with SLNM of the central neck in PTMC.

PMID- 24562935
TI  - DHCR24 is an independent predictor of progression in patients with non-muscle
      invasive urothelial carcinoma, and its functional role is involved in the
      aggressive properties of urothelial carcinoma cells.
AB  - PURPOSE: The DHCR24 gene that encodes 3b-hydroxysterol Delta24-reductase, an
      oxidoreductase involved in cholesterol biosynthesis, has been identified as a
      progression-related gene based on the quantitative real-time PCR (qPCR) gene
      signature. Here, the functional role of DHCR24 and its clinical relevance in non
      muscle-invasive urothelial carcinoma (NMIUC) were investigated. METHODS: Primary
      NMIUC tissue specimens (n = 162) were analyzed by qPCR. Immunohistochemical
      staining was also performed on 63 subsets of NMIUC tissues. The present study was
      also undertaken in order to verify the effect of DHCR24 on human urothelial
      carcinoma cells. RESULTS: The mRNA expression levels of DHCR24 were significantly
      higher for patients in with higher grades of tumors than for those with lower
      grades of tumors (P = 0.003). Kaplan-Meier estimates revealed significant
      differences in the time to progression between low- and high-mRNA expression
      groups (log-rank test, P < 0.001). Multivariate Cox regression analysis revealed
      that the level of DHCR24 expression is an independent predictor of progression
      (hazard ratio, 5.464; 95 % confidence interval, 1.746-17.099; P = 0.004). The
      results of immunohistochemical staining were generally concordant with mRNA
      expression levels. Enforced expression of DHCR24 caused proliferation, adhesion,
      and migration, while DHCR24 loss resulted in slower proliferation and a reduction
      in cell viabilities compared with control cells. CONCLUSIONS: DHCR24 was found to
      be closely associated with progression among patients with NMIUC and showed
      aggressive properties in human UC cells.

PMID- 24562936
TI  - Expression of B7-H3, a potential factor of tumor immune evasion in combination
      with the number of regulatory T cells, affects against recurrence-free survival
      in breast cancer patients.
AB  - BACKGROUND: In the tumor microenvironment, factors inhibiting the targeting of
      cancer cells by activated T cells have recently been noted. B7-H3 belongs to the
      B7 superfamily of immune regulatory ligands and plays an important role in the
      adaptive immune response of co-inhibitory/stimulatory factors in regulating T
      cells. However, the degree to which B7-H3 directly affects tumor immune evasion
      mechanisms remains unclear, particularly in patients with breast cancer.
      Regulatory T cells (Tregs) are known as a key player in the inhibition of immune
      mechanisms. The present study demonstrated that expression of B7-H3 on tumor
      cells and the number of Tregs in the tumor microenvironment independently
      affected prognosis in breast cancer patients. METHODS: We immunohistochemically
      investigated the presence of B7-H3 and forkhead box P3 (Foxp3)-positive Tregs in
      pathological specimens from 90 patients with breast cancer. RESULTS: Positive B7
      H3 expression was associated with shorter recurrence-free survival (RFS) (p =
      0.014). A higher percentage of Foxp3-positive cells also correlated with shorter
      RFS (p = 0.039). Multivariate analysis showed B7-H3 as an independent factor on
      RFS. Foxp3 expression in tumor-infiltrating lymphocytes (TILs) correlated
      significantly with larger tumor size (>2 cm), expression of human epidermal
      growth factor receptor 2 (HER2), and higher nuclear grade (p = 0.003, p < 0.001,
      p = 0.001, respectively). No correlation was identified between expression of B7
      H3 and the percentage of Foxp3-positive TILs. CONCLUSIONS: B7-H3 and Foxp3 can be
      regarded as markers of poor prognosis in breast cancer. These expressions were
      not correlated, suggesting that B7-H3 expression plays an independent role in
      tumor immune evasion, regardless of Tregs.

PMID- 24562937
TI  - Clinical implication of morphological subtypes in management of intraductal
      papillary mucinous neoplasm.
AB  - PURPOSE: Morphological subtypes of intraductal papillary mucinous neoplasm (IPMN)
      have been established. Invasive IPMNs include colloid carcinoma and tubular
      carcinoma. Few studies have explored the association between the morphological
      and invasive subtypes in a large population. Clinical relevance of the
      morphological subtypes remains unclear. METHODS: One hundred sixty-nine
      consecutive patients who underwent curative resection of IPMN were enrolled. The
      intraductal components were classified into four distinct epithelial subtypes:
      gastric, intestinal, pancreatobiliary, and oncocytic. The invasive components
      were classified as colloid or tubular. RESULTS: The numbers of patients with
      gastric, intestinal, pancreatobiliary, and oncocytic subtypes were 123, 42, 3,
      and 1, respectively. Fifty-six patients had invasive cancer (tubular type, 42;
      colloid type, 14). The proportions of gastric type IPMN within each histological
      grade were 88 % among adenomas, 43 % among noninvasive carcinomas, 41 % among
      minimally invasive carcinomas, and 74 % among invasive carcinomas. Gastric
      subtype was more commonly associated with branch duct type and intestinal subtype
      with main duct type, and these tendencies were statistically significant (P =
      0.0131). Furthermore, there was a strong correlation between gastric and tubular
      types and between intestinal and colloid types (P < 0.0001). The 5-year survival
      rate among the 56 invasive cancers was 52.7 % for gastric type and 89.7 % for
      intestinal type, which was statistically significant (P = 0.030). CONCLUSIONS:
      Gastric type IPMN is mostly derived from branch duct IPMN and often demonstrates
      benign behavior, as seen with adenomas. However, once gastric type IPMN develops
      into invasive carcinoma, the survival rate is significantly lower than other
      types.

PMID- 24562939
TI  - Is preoperative colonoscopy necessary for patients undergoing gastric cancer
      surgery?
AB  - PURPOSE: The aim of this study was to evaluate the necessity of preoperative
      colonoscopy (CS) in gastric cancer (GC) patients and to assess the outcomes of
      different treatments in patients with synchronous GC and colorectal neoplasms
      (CRN). We also determined the risk factors influencing the comorbidity of
      colorectal cancer (CRC) in patients with GC. METHODS: This retrospective study
      included 1891 consecutive GC patients who underwent CS before surgery from
      January 1, 1999, through June 30, 2012. RESULTS: There was a high prevalence of
      concurrent CRN (28.4 %) and CRC (3.2 %) in our patients with GC. Sixty-one
      patients with GC had synchronous CRC. Twenty-three of the 61 tumors were
      perioperatively treated by endoscopic resection. The other 38 tumors were treated
      by simultaneous surgery for the GC and CRC. Surgical complications were not found
      in either the endoscopic or surgical resection group. The multivariate logistic
      regression analysis indicated that the prevalence of synchronous CRC in patients
      with GC was significantly associated with the incidence of multiple GCs [P <
      0.0001; odds ratio (OR) 15.3], having anemia (P = 0.002; OR 3.0), and having a
      smoking history (P = 0.021; OR 1.9). CONCLUSIONS: We recommend preoperative CS
      screening for GC patients. In particular, preoperative CS screening is
      indispensable for patients with multiple GCs. In addition, simultaneous
      treatments for patients with synchronous GC and CRN are safe and feasible
      procedures.

PMID- 24562938
TI  - Long-term clinical and functional results of intersphincteric resection for lower
      rectal cancer.
AB  - BACKGROUND: Intersphincteric resection (ISR) is an alternative to
      abdominoperineal resection (APR) for super-low rectal cancer. The aim of this
      study was to evaluate the long-term curability after ISR over an average 6-year
      observational period, to compare the postoperative functional outcomes for ISR
      with those for low anterior resection (LAR), and to determine whether ISR is a
      function-preserving surgery. METHODS: Between 2000 and 2007, a total of 77
      consecutive patients with low rectal cancer underwent curative ISR. The
      curability outcomes for ISR, LAR, and APR were compared. We evaluated the
      postoperative defecation functions, Wexner incontinence score (WIS), and
      defecation quality of life (QOL) for a between-groups comparison (ISR/LAR).
      RESULTS: The 5-year survival rate after ISR was 76.4 %, and the outcome was
      better than for APR (APR 51.2 %, LAR 80.7 %). Local recurrence after ISR occurred
      in 7.8 % of patients (APR 12.1 %, LAR 11.7 %). The average daily frequency of
      defecation was 3.7 times for the ISR patients and 3.2 times for the LAR patients,
      indicating no significant difference between the groups. Moreover, there were no
      significant differences between the groups for defecation functions. The WIS was
      8.1 for ISR and 4.9 for LAR, and the defecation QOL for ISR and LAR was not
      significantly different (modified fecal incontinence QOL score: ISR 34.3, LAR
      26.5). CONCLUSIONS: The long-term clinical and functional results suggest that
      ISR may be the optimal sphincter-preserving surgery for patients with lower
      rectal cancers who cannot be treated with a double-stapling technique.

PMID- 24562968
TI  - Do psychosocial job demands and job resources predict long-term sickness absence?
      An analysis of register-based outcomes using pooled data on 39,408 individuals in
      four occupational groups.
AB  - PURPOSE: To investigate whether psychosocial job demands (work pace and
      quantitative demands) and job resources (influence at work and quality of
      leadership) predict long-term sickness absence (LTSA) for more than three
      consecutive weeks in four occupational groups. METHODS: Survey data pooling
      39,408 respondents were fitted to a national register containing information on
      payments of sickness absence compensation. Using multi-adjusted Cox regression,
      respondents were followed for an 18-month follow-up period to assess risk of
      LTSA. RESULTS: In the entire study population, low and medium levels of influence
      at work and low quality of leadership predicted a significantly increased risk of
      LTSA, whereas medium levels of quantitative demands predicted a significantly
      reduced risk of LTSA. For employees working with clients and for office workers,
      low and medium influence at work associated with a significantly increased risk
      of LTSA. For employees working with clients, low quality of leadership predicted
      a significantly increased risk of LTSA. For manual workers, low influence at work
      predicted a significantly increased risk of LTSA and medium quantitative demands
      were associated with a significantly reduced risk of LTSA. For employees working
      with customers, medium quantitative demands predicted a significantly reduced
      risk of LTSA. Finally, in predicting LTSA, we found significant interaction
      effects between job demands and job resources. CONCLUSIONS: The study indicates
      that a lack of job resources--particularly influence at work--are more important
      predictors of LTSA than high job demands.

PMID- 24562970
TI  - Diabetes and colorectal cancer screening among men and women in the USA: National
      Health Interview Survey: 2008, 2010.
AB  - PURPOSE: Adults with diabetes are at increased risk of being diagnosed with and
      dying from colorectal cancer, but it is unclear whether colorectal cancer
      screening (CRCS) use is lower in this population. Using the 2008 and 2010
      National Health Interview Survey data, we examined whether guideline-concordant
      CRCS is lower among men and women with self-reported diabetes. METHODS: We
      calculated the weighted percentage of guideline-concordant CRCS and unadjusted
      and adjusted prevalence ratios (PR) comparing adults aged 51-75 years with
      diabetes (n = 6,514) to those without (n = 8,371). We also examined effect
      modification by age (51-64 and 65-75), race/ethnicity, and number of medical
      office visits (0-3, >= 4). RESULTS: The unadjusted prevalence of CRCS among men
      with diabetes was significantly higher than men without (63.3 vs. 58.0 %; PR =
      1.09 95 % CI 1.03-1.16). In adjusted models, this relationship was evident among
      older [adjusted PR (aPR) = 1.13 95 % CI 1.06-1.21] but not younger men (aPR =
      0.99 95 % CI 0.91-1.08; p for interaction term <= 0.01). There was no significant
      association between diabetes and CRCS among women overall (56.6 vs. 57.9 %; PR =
      0.98 95 % CI 0.92-1.04) or by age group. Race/ethnicity and the number of medical
      visits did not significantly modify the association between diabetes and CRCS for
      men or women. CONCLUSIONS: Men and women with self-reported diabetes were not
      less likely to be up to date with CRCS than those without diabetes. Older men
      with diabetes were more likely to be up to date with CRCS than those without
      diabetes.

PMID- 24562969
TI  - Methamphetamine-induced neurotoxicity disrupts pharmacologically evoked dopamine
      transients in the dorsomedial and dorsolateral striatum.
AB  - Phasic dopamine (DA) signaling, during which burst firing by DA neurons generates
      short-lived elevations in extracellular DA in terminal fields called DA
      transients, is implicated in reinforcement learning. Disrupted phasic DA
      signaling is proposed to link DA depletions and cognitive-behavioral impairment
      in methamphetamine (METH)-induced neurotoxicity. Here, we further investigated
      this disruption by assessing effects of METH pretreatment on DA transients
      elicited by a drug cocktail of raclopride, a D2 DA receptor antagonist, and
      nomifensine, an inhibitor of the dopamine transporter (DAT). One advantage of
      this approach is that pharmacological activation provides a large, high-quality
      data set of transients elicited by endogenous burst firing of DA neurons for
      analysis of regional differences and neurotoxicity. These pharmacologically
      evoked DA transients were measured in the dorsomedial (DM) and dorsolateral (DL)
      striatum of urethane-anesthetized rats by fast-scan cyclic voltammetry.
      Electrically evoked DA levels were also recorded to quantify DA release and
      uptake, and DAT binding was determined by means of autoradiography to index DA
      denervation. Pharmacologically evoked DA transients in intact animals exhibited a
      greater amplitude and frequency and shorter duration in the DM compared to the DL
      striatum, despite similar pre- and post-drug assessments of DA release and uptake
      in both sub-regions as determined from the electrically evoked DA signals. METH
      pretreatment reduced transient activity. The most prominent effect of METH
      pretreatment on transients across striatal sub-region was decreased amplitude,
      which mirrored decreased DAT binding and was accompanied by decreased DA release.
      Overall, these results identify marked intrastriatal differences in the activity
      of DA transients that appear independent of presynaptic mechanisms for DA release
      and uptake and further support disrupted phasic DA signaling mediated by
      decreased DA release in rats with METH-induced neurotoxicity.

PMID- 24562972
TI  - Dispersion of U-series natural radionuclides in stream sediments from Edale, UK.
AB  - The spatial distribution of (238)U-series radionuclides, specifically 238U, 234U,
      230Th and 226Ra, has been determined in stream sediments from Edale, Derbyshire,
      United Kingdom, to explore the behaviour of U-series radionuclides during
      weathering. For uranium and thorium, two different extraction methods were used,
      total dissolution with HNO3/HF in a microwave and leaching with aqua regia. This
      was followed by radiochemical separation using extraction chromatography, then
      alpha spectrometry measurement. The total radium contents in the sediments were
      measured using gamma spectrometry, while the leached fraction was measured in the
      same way as for uranium and thorium. The total sediment content of uranium and
      thorium ranges from ~10 up to ~200 Bq kg(-1), while the radium specific activity
      lies between ~15 and 180 Bq kg(-1). In the aqua regia extractions, the uranium
      and thorium contents are in the range of ~5 to ~100 Bq kg(-1), while the radium
      specific activities are similar to those measured by total dissolution. All the
      radionuclides show no correlation with organic matter content. The activity
      ratios 234U/238U, 230Th/238U and 226Ra/238U were used to determine the degree of
      radioactive disequilibrium. The data show disequilibrium in most of the
      sediments, with activity ratios of 234U/238U, 230Th/238U and 226Ra/238U>1,
      inconsistent with evolution through straightforward weathering processes.
      Multivariate cluster analysis based on five variables, the specific activities of
      238U, 234U, 230Th, 226Ra and loss on ignition, was employed to group the data and
      identify five distinct clusters. There seems to be a link between high
      radionuclide concentrations and proximity to landslips.

PMID- 24562973
TI  - A gene cluster for the synthesis of serotype g-specific polysaccharide antigen in
      Aggregatibacter actinomycetemcomitans.
AB  - Aggregatibacter actinomycetemcomitans is an important pathogen related to
      aggressively progressive periodontal breakdown in adolescents and adults. The
      species can be divided into six serotypes (a-f) according to their surface
      carbohydrate antigens. Recently, a new serotype g of A. actinomycetemcomitans was
      proposed. The aim of the present study was to sequence the gene cluster
      associated with the biosynthesis of the serotype g-specific polysaccharide
      antigen and develop serotype-specific primers for PCR assay to identify serotype
      g strains of A. actinomycetemcomitans. The serotype-specific polysaccharide
      (SSPS) gene cluster of the NUM-Aa 4039 strain contained 21 genes in 21,842-bp
      nucleotides. The similarity of the SSPS gene cluster sequence was 96.7 % compared
      with that of the serotype e strain. Seventeen serotype g genes showed more than
      90 % homology both in nucleotide and amino acids to the serotype e strain. Three
      additional genes with 1,579 bp in NUM-Aa 4039 were inserted into the
      corresponding ORF13 of the serotype e strain. The serotype g-specific primers
      were designed from the insertion region of NUM-Aa 4039. Serotypes of the a-f
      strains were not amplified by serotype-specific g primers; only NUM-Aa 4039
      showed an amplicon band. The NUM-Aa 4039 strain was three genes in the SSPS gene
      cluster different from those of serotype e strain. The specific primers derived
      from these different regions are useful for identification and distribution of
      serotype g strain among A. actinomycetemcomitans from clinical samples. 

PMID- 24562974
TI  - Information on risk of constipation for Danish users of opioids, and their
      laxative use.
AB  - BACKGROUND: While it is well known that use of opioids often cause constipation,
      little is known about the information given to patients regarding this potential
      side-effect and their use of laxatives to prevent it. OBJECTIVE: To assess the
      degree of information provided by the prescriber to users of opioids by the time
      of the first prescription regarding the risk of constipation. METHOD: Interviews
      with patients filling an opioid at a community pharmacy were performed by the
      dispensing pharmacist or pharmaconomist at the pharmacy. Information collected
      concerned the patient, the opioid, information received regarding constipation,
      current constipation and current laxative treatment. RESULTS: A total of 286
      interviews were completed. Overall, 28.3 % remembered having received information
      about the risk of constipation by the time of the first prescription. Excluding
      49 first-time opioid users, we found 91 laxative users and 146 non-laxative
      users, of whom 73.6 and 4.8 %, respectively, currently experienced constipation.
      CONCLUSION: Only a small proportion of patients with a prescription for opioids
      remembered having had information on potential constipation caused by opioids and
      having received any recommendation on how to use laxatives to prevent
      constipation. Interventions should focus on whether constipation is present and
      on rational use of laxatives.

PMID- 24562971
TI  - Genetic variation in vitamin D-related genes and risk of colorectal cancer in
      African Americans.
AB  - PURPOSE: Disparities in both colorectal cancer (CRC) incidence and survival
      impact African Americans (AAs) more than other US ethnic groups. Because vitamin
      D is thought to protect against CRC and AAs have lower serum vitamin D levels,
      genetic variants that modulate the levels of active hormone in the tissues could
      explain some of the cancer health disparity. Consequently, we hypothesized that
      genetic variants in vitamin D-related genes are associated with CRC risk.
      METHODS: To test this hypothesis, we studied 39 potentially functional single
      nucleotide polymorphisms (SNPs) in eight genes (CYP2R1, CYP3A4, CYP24A1, CYP27A1,
      CYP27B1, GC, DHCR7, and VDR) in 961 AA CRC cases and 838 healthy AA controls from
      Chicago and North Carolina. We tested whether SNPs are associated with CRC
      incidence using logistic regression models to calculate p values, odds ratios,
      and 95 % confidence intervals. In the logistic regression, we used a log-additive
      genetic model and used age, gender, and percent West African ancestry, which we
      estimated with the program STRUCTURE, as covariates in the models. RESULTS: A
      nominally significant association was detected between CRC and the SNP rs12794714
      in the vitamin D 25-hydroxylase gene CYP2R1 (p = 0.019), a SNP that has
      previously been associated with serum vitamin D levels. Two SNPs, rs16847024 in
      the GC gene and rs6022990 in the CYP24A1 gene, were nominally associated with
      left-sided CRC (p = 0.015 and p = 0.018, respectively). CONCLUSIONS: Our results
      strongly suggest that genetic variation in vitamin D-related genes could affect
      CRC susceptibility in AAs.

PMID- 24562975
TI  - Identification and evaluation of drug-supplement interactions in Hungarian
      hospital patients.
AB  - BACKGROUND: The increasing number of patients taking supplementary products
      together with prescribed medicines has become a new challenge for health care
      systems. These products may influence therapy outcomes by inducing unwanted
      effects. Particularly concerning is the potential for harmful interactions
      between prescribed medicines and supplementary products. OBJECTIVE: The aims of
      the study were to evaluate supplement use, to identify and analyse potential
      interactions, and to assess the efficiency of computerised interaction screening.
      SETTING: Participants of the study were inpatients and outpatients of a Hungarian
      university hospital. METHOD: A cross-sectional point-of-care survey of 200
      patients was carried out. Data was collected through personal interviews and a
      review of the medical records. Drug-drug, drug-supplement and supplement
      supplement interactions were analysed with three interaction databases (Lexi
      Interact Online, Medscape Drug Interaction Checker and Mediris). MAIN OUTCOME
      MEASURE: Prevalence of supplementary product use, number of medicines and
      supplementary products per patient, procurement sources of products, number of
      potentially severe interactions. RESULTS: There was a marked difference between
      data obtained from patient interviews and the medical records. 85.5 % of the
      surveyed patients took supplementary products during the 2 weeks prior to the
      interview. The average number of prescribed medicines and supplementary products
      were 7.8 and 2.5, respectively. Women were more likely to take supplements than
      men. There was no significant difference in supplement use between patients under
      or over 60 years, between inpatients and outpatients and among patients in
      various wards. 39.4 % of supplementary products were purchased outside a
      regulated pharmacy environment. Potentially severe drug-supplement interactions
      were detected with 45.2 % of supplement users; however the majority of
      interactions were not included in one or the other of the three databases. In
      addition to that the risk ratings of the same interactions varied greatly between
      databases. CONCLUSION: A significant number of patients are exposed to potential
      drug interactions with supplementary products; however interagreement among
      interaction databases is poor. Our data suggest that a full medication history
      should specifically address the intake of supplements.

PMID- 24562976
TI  - Adverse drug reactions associated with asthma medications in children: systematic
      review of clinical trials.
AB  - BACKGROUND: Respiratory medications are frequently prescribed for use in
      children. Several studies have reported information on the safety of asthma
      medications in clinical studies in adults, but information about safety in
      children is scarce. OBJECTIVE: To review published clinical trials on the
      occurrence and characteristics of adverse drug reactions (ADRs) in children,
      reported for asthma medications licensed for paediatric use. METHODS: We
      systematically reviewed the literature following the Preferred Reporting Items
      for Systematic Reviews and Meta-Analyses statement guidelines. PubMed, Embase,
      Cochrane Library, PsycINFO, IPA, and CINAHLs databases were searched from origin
      until July 2013 for studies reporting ADRs for beta2-receptor agonists, inhaled
      corticosteroids, leukotriene receptor antagonists and combination products in
      children from birth to age 17. Information on ADR reporting rates, age and
      gender, type and seriousness of ADRs, design, setting, observation period, type
      of assessors, and funding sources was extracted from the articles. RESULTS:
      Literature searches resulted in 162 potential relevant articles. However only 12
      of these studies were included in this review as they reported information about
      ADR rates from use of salmeterol, formoterol, fluticasone, montelukast,
      zafirlukast and budesonide/formoterol in children. The total population was
      approximately 3,000 children; the majority was 6- to 11-year-olds and two thirds
      of these were boys. The observation period varied from 1 to 22 months. The most
      frequently reported ADRs were exacerbation of asthma, respiratory tract
      infection, cough, fever and headache. Only few ADRs were rated as being serious,
      however a number of children dropped out of the clinical trials due to serious
      ADRs, and, therefore, the real number of serious ADRs is probably higher.
      CONCLUSIONS: Few clinical trials reporting ADRs from use of asthma medications in
      children were identified in the literature. These studies reported only a few
      types of ADRs, the majority being non-serious.

PMID- 24562977
TI  - Clinical services for obstructive sleep apnea patients in pharmacies: the
      Australian experience.
AB  - BACKGROUND: In Australia, certain pharmacies have undertaken a role in the
      management of the chronic sleep disorder, obstructive sleep apnea. The
      perspectives of pharmacy staff involved in this niche clinical service have never
      been formally collated on a national scale. The experiences of Australian
      pharmacies could provide a template for pharmacies in other health systems to
      adopt similar roles. OBJECTIVE: To provide an overview of the perspectives of
      pharmacy staff involved in Continuous Positive Airway Pressure (CPAP) and sleep
      apnea-related services. Specifically, to describe clinical and structural
      elements, explore benefits and barriers, investigate viability, and gauge
      perspectives on future directions. SETTING: Australian community pharmacies
      involved in CPAP and sleep apnea-related services. METHOD: Cross-sectional mail
      survey. A questionnaire designed to meet the study objectives was developed by
      the researchers and mailed to all pharmacies in Australia providing CPAP services
      during the period of study recruitment. Pharmacies were identified through the
      distributor lists of the major CPAP manufacturers and a comprehensive Internet
      search. Non-responders were contacted in two subsequent recruitment rounds. MAIN
      OUTCOME MEASURE: Self-reported sleep apnea service specifics. RESULTS: A response
      rate of 55 % was achieved (n = 106 questionnaires valid for data entry). Benefits
      of providing a CPAP service included meeting patient and community needs, and
      professional satisfaction. Barriers included the cost of CPAP equipment to
      patients and lack of time. A majority of pharmacies (71 %) reported the service
      was financially viable despite most (63 %) not charging a 'fee for service.'
      Respondents expressed the view that CPAP provision should remain a specialist
      area of practice within the pharmacy profession. Key areas identified for
      improvement within the service were: (1) Staff training and knowledge (2)
      Promotion of the service and increasing public awareness (3) Infrastructure and
      expansion (4) Inter-professional collaboration and communication (5) Patient
      follow-up. CONCLUSION: The provision of CPAP and sleep apnea-related services can
      be a viable and rewarding experience for pharmacists. The role may need to remain
      a specialised area for those willing to invest significantly in the service--in
      time, staff, resources and finances.

PMID- 24562978
TI  - Expression of avian influenza virus (H5N1) hemagglutinin and matrix protein 1 in
      Pichia pastoris and evaluation of their immunogenicity in mice.
AB  - The conventional avian influenza vaccines rely on development of neutralizing
      antibodies against the HA and NA antigens. However, these antigens are highly
      variable, and hence there is a need for better vaccine candidates which would
      offer broader protection in animals. The M1 of avian influenza is another major
      structural protein that has conserved epitopes that are reported to induce CD8+ T
      cells and can contribute to protection against morbidity and mortality from
      influenza. Hence in an effort to study the immune response of rM1 either alone or
      in combination with rHA, the hemagglutinin (HA) and matrix protein (M1) of
      A/Hatay/2004/H5N1 strain of avian influenza were expressed in Pichia pastoris as
      his-tagged proteins and purified through Ni-NTA chromatography. The His-tag was
      removed using TEV protease cleavage site and the immunogenicity of purified rHA
      and rM1 either alone or in combination was determined in mice. One group of mice
      was immunized with 5 MUg of purified rHA, the other group was immunized with rM1,
      and a third group of mice were immunized with 5 MUg of rHA and rM1. All the
      animals were boosted twice, once on 28 days postimmunization (dpi) and the second
      on 42 dpi. The immune response was evaluated by enzyme-linked immunosorbent assay
      (ELISA) and hemagglutination inhibition (HI) assay. The group of mice immunized
      with rHA and rM1 together showed significantly higher immune response against rHA
      and rM1 than mice immunized with either HA or M1 antigens. The addition of rM1
      with rHA resulted in increased HI titer in animals immunized with both the
      antigens. These results suggest that the HA and M1 expressed in P. pastoris can
      be utilized in combination for the development of faster and cost-effective
      vaccines for circulating and newer strains of avian influenza and would aid in
      combating the disease in a pandemic situation, in which production time matters
      greatly. 

PMID- 24562979
TI  - Biohydrogen production through dark fermentation by a microbial consortium using
      whey permeate as substrate.
AB  - Nowadays, hydrogen produced globally has been synthesized from fossil fuel with
      limited source. Therefore, research has been developed in order to explore
      biological H2 production by dark fermentation. The purpose of this work was to
      evaluate the effect of initial pH and ferrous sulfate and ammonium sulfate
      concentrations on the production of biohydrogen by dark fermentation. The process
      was carried out in batch mode under anaerobic conditions, in the absence of
      light, and at standard room temperature and pressure. A microbial consortium
      provided by the effluent treatment plant of a local dairy company was inoculated
      into a synthetic medium supplemented with cheese whey permeate (20 g/L of
      lactose) as a carbon source. The influence of three variables was analyzed by a
      central composite design 2((3)), and the optimum results of hydrogen yield (4.13
      mol H2/mol lactose) and productivity (86.31 mmol H2/L/day) were achieved at
      initial pH 7.0 and FeSO4 and (NH4)2SO4 concentrations of 0.6 and 1.5 g/L,
      respectively. Under these conditions, the kinetic parameters of fermentation were
      investigated by analyzing the profile of H2 yield and productivity, metabolite
      concentrations, pH, and concentration of dissolved iron. In the kinetic analysis,
      the modified Gompertz equation described adequately the fermentative hydrogen
      production from cheese whey permeate (R (2) = 0.98). The profile of ethanol and
      volatile organic acids showed that lactic acid and butyric acid were the main
      metabolites produced, and the sum of both by-products corresponded to about 58 %
      of the total metabolites. 

PMID- 24562980
TI  - Exploring thermophilic cellulolytic enzyme production potential of Aspergillus
      fumigatus by the solid-state fermentation of wheat straw.
AB  - Cellulases can be used for biofuel production to decrease the fuel crises in the
      world. Microorganisms cultured on lignocellulosic wastes can be used for the
      production of cellulolytic enzymes at large scale. In the current study,
      cellulolytic enzyme production potential of Aspergillus fumigatus was explored
      and optimized by employing various cultural and nutritional parameters. Maximum
      endoglucanase production was observed after 72 h at 55  degrees C, pH 5.5, and 70
      % moisture level. Addition of 0.3 % of fructose, peptone, and Tween-80 further
      enhanced the production of endoglucanase. Maximum purification was achieved with
      40 % ammonium sulfate, and it was purified 2.63-fold by gel filtration
      chromatography. Endoglucanase has 55  degrees C optimum temperature, 4.8 optimum
      pH, 3.97 mM K m, and 8.53 MUM/mL/min V max. Maximum exoglucanase production was
      observed at 55  degrees C after 72 h, at pH 5.5, and 70 % moisture level. Further
      addition of 0.3 % of each of fructose, peptone, and Tween-80 enhances the
      secretion of endoglucanase. It was purified 3.30-fold in the presence of 40 %
      ammonium sulfate followed by gel filtration chromatography. Its optimum
      temperature was 55  degrees C, optimum pH was 4.8, 4.34 mM K m, and 7.29
      MUM/mL/min V max. In the case of beta-glucosidase, maximum activity was observed
      after 72 h at 55  degrees C, pH 5.5, and 70 % moisture level. The presence of 0.3
      % of fructose, peptone, and Tween-80 in media has beneficial impact on beta
      glucosidase production. A 4.36-fold purification was achieved by 40 % ammonium
      sulfate precipitation and gel filtration chromatography. Optimum temperature of
      beta-glucosidase was 55  degrees C, optimum pH was 4.8, K m was 4.92 mM, and V
      max 6.75 MUM/mL/min. It was also observed that fructose is better than glucose,
      and peptone is better than urea for the growth of A. fumigatus. The K m and V max
      values indicated that endoglucanase, exoglucanase, and beta-glucosidase have good
      affinity for their substrates. 

PMID- 24562982
TI  - Sequential extrusion-ozone pretreatment of switchgrass and big bluestem.
AB  - Pretreatment is one of the biggest challenges in utilizing lignocellulosic
      feedstocks to meet the mandatory requirements for biofuels around the world.
      Earlier researchers evaluated extrusion and ozone pretreatment separately and
      found that sugar recovery can be improved significantly from 15-20 to 40-75 % for
      different feedstocks. To further improve sugar recoveries, extrusion-ozone
      sequential pretreatment was explored. Accordingly, optimal extruded switchgrass
      (176  degrees C, 155 rpm, 20 % moisture, and 8 mm) and big bluestem (180  degrees
      C, 155 rpm, 20 % moisture, and 8 mm) at 25-75 % moisture content were exposed to
      an ozone flow rate of 37-365 mg/h for 2.5 to 10 min. Pretreated samples were then
      subjected to enzymatic hydrolysis to determine sugar recovery. Statistical
      analyses confirmed significant effects of the independent variables and their
      interactions on sugar recoveries for both feedstocks. Maximum glucose, xylose,
      and total sugar recovery of 66.4, 82.3, and 70.4 %, respectively, were obtained
      when a low-moisture (25 %) extruded switchgrass was ozonated for 2.5 min at a
      flow rate of 37 mg/h. Respectively, this represents increases of 3.42, 5.01, and
      3.42 times that of the control. When big bluestem at 25 % moisture was extruded
      and then ozonated for 2.5 min at a flow rate of 365 mg/h, resulting glucose,
      xylose, and total sugar recoveries of 90.8, 92.2, and 87.5 %, respectively, were
      obtained. These represent increases of 4.5, 2.7, and 3.9 times than that of the
      control. It is also noteworthy that furfural and hydroxymethyl furfural were not
      detected in any of the pretreatments, and only low levels (0.14-0.18 g/l) of
      acetic acid were measured. The results show that sequential pretreatment using
      extrusion and ozone is an efficient way to improve sugar recovery from herbaceous
      biomass feedstocks. 

PMID- 24562983
TI  - Supratentorial ependymomas of childhood carry C11orf95-RELA fusions leading to
      pathological activation of the NF-kappaB signaling pathway.

PMID- 24562984
TI  - An ecological momentary assessment of lapse occurrences in dieters.
AB  - PURPOSE: The aim of this study is to investigate the factors related to dietary
      lapse occurrence in a community sample of dieters. METHODS: An ecological
      momentary assessment (EMA) methodology, via mobile phone-based diaries, was
      employed to record dietary lapse occurrences in a group of dieters (N = 80; M age
      = 41.21 +/- 15.60 years; M BMI = 30.78 +/- 7.26) over 7 days. RESULTS: Analyses
      indicated that lapses were positively associated with the strength of dietary
      temptation, presence of others, coping responses, and the environment (exposure
      to food cues) in which the dieters were in; lapses were more likely to occur in
      the evening and were negatively associated with the use of coping mechanisms.
      Additionally, lapse occurrence was found to mediate the relationships among the
      above predictors of lapse and the self-efficacy to resist future dietary
      temptations. CONCLUSIONS: Results provide an insight into the occurrence of
      lapses in dieters and have implications for interventions focusing on weight loss
      maintenance and relapse prevention.

PMID- 24562985
TI  - Non-invasive cardiac output evaluation in postoperative cardiac surgery patients,
      using a new prolonged expiration-based technique.
AB  - The gold standard methods to measure cardiac output (CO) are invasive and expose
      the patient to high risks of various complications. The aim of this study is to
      assess an innovative non-invasive method for CO monitoring in mechanically
      ventilated patients after cardiac surgery and its agreement with values obtained
      by thermodilution technique. Continuous monitoring of respiratory gas
      concentrations and airflow allows the estimation of CO through a newly developed
      algorithm derived from a modified version of the Fick equation. It consists of
      two phases: the first involves measurements during steady breathing state, and
      the second starts when a sudden perturbation into the carbon dioxide elimination
      process is introduced by a prolonged expiration. This prospective clinical study
      involved thirty-five adult patients, undergone cardiac surgery. The measurements
      were performed in curarized and haemodynamically stable patients, during the post
      surgery recovery in intensive care unit. The study protocol, which lasted 1 h for
      each patient, consisted of 20 measurements obtained by prolonged expiration-based
      method and 10 by thermodilution. The estimation of CO using the proposed method
      (COK) agreed with the thermodilution (COT) as demonstrated by: a low mean bias
      between COK and COT considering all patients (i.e., -0.11 L min(-1)); a best
      fitting line having slope = 0.98, r = 0.81, p < 0.0001; the lower and upper
      limits of agreement were -0.77 and +0.54 L min(-1), respectively. COK shows a
      mean percentage error of 34 %. In stable mechanically ventilated patients,
      undergone cardiac surgery, the proposed method is reliable if compared to the
      thermodilution. Considering the non-invasivity of the technique, further
      evaluations of its performances are encouraged. 

PMID- 24563009
TI  - Quasiparticle self-consistent GW method for the spectral properties of complex
      materials.
AB  - The GW approximation to the formally exact many-body perturbation theory has been
      applied successfully to materials for several decades. Since the practical
      calculations are extremely cumbersome, the GW self-energy is most commonly
      evaluated using a first-order perturbative approach: This is the so-called G 0 W
      0 scheme. However, the G 0 W 0 approximation depends heavily on the mean-field
      theory that is employed as a basis for the perturbation theory. Recently, a
      procedure to reach a kind of self-consistency within the GW framework has been
      proposed. The quasiparticle self-consistent GW (QSGW) approximation retains some
      positive aspects of a self-consistent approach, but circumvents the intricacies
      of the complete GW theory, which is inconveniently based on a non-Hermitian and
      dynamical self-energy. This new scheme allows one to surmount most of the flaws
      of the usual G 0 W 0 at a moderate calculation cost and at a reasonable
      implementation burden. In particular, the issues of small band gap
      semiconductors, of large band gap insulators, and of some transition metal oxides
      are then cured. The QSGW method broadens the range of materials for which the
      spectral properties can be predicted with confidence. 

PMID- 24563010
TI  - Single rotating molecule-machines: nanovehicles and molecular motors.
AB  - In the last decade many molecular machines with controlled molecular motions have
      been synthesized. In the present review chapter we will present and discuss our
      contribution to the field, in particular through some examples of rotating
      molecular machines that have been designed, synthesized, and studied in our
      group. After starting by explaining why it is so important to study such machines
      as single molecules, we will focus on two families of molecular machines,
      nanovehicles and molecular motors. The first members of the nanovehicle family
      are molecules with two triptycenes as wheels: the axle and the wheelbarrow. Then
      come the four-wheel nanocars. Since triptycene wheels are not very mobile on
      metallic surfaces, alternative wheels with a bowl-shape structure have also been
      synthesized and studied on surfaces. The molecular motors are built around
      ruthenium organometallic centers and have a piano-stool geometry with peripheric
      ferrocenyl groups. 

PMID- 24563008
TI  - Scar tissue and microvolt T-wave alternans.
AB  - Microvolt T-wave alternans (MTWA) is an electrocardiographic marker for
      predicting sudden cardiac death. In this study, we aimed to study the relation
      between MTWA and scar assessed with cardiac magnetic resonance imaging (CMR) in
      patients with ischemic cardiomyopathy (ICM) or dilated cardiomyopathy (DCM).
      Sixty-eight patients with positive or negative MTWA and analysable CMR
      examination were included. Using CMR and the delayed enhancement technique, left
      ventricular ejection fraction (LVEF), volumes, wall motion and scar
      characteristics were assessed. Overall, positive MTWA (n = 40) was related to
      male gender (p = 0.04), lower LVEF (p = 0.04) and increased left ventricular end
      diastolic volume (LVEDV) (p < 0.01). After multivariate analysis, male gender (p
      = 0.01) and lower LVEF remained significant (p = 0.02). Scar characteristics
      (presence, transmurality, and scar score) were not related to MTWA (all p > 0.5).
      In the patients with ICM (n = 40) scar was detected in 38. Positive MTWA (n = 18)
      was related to higher LVEDV (p = 0.05). In patients with DCM (n = 28), scar was
      detected in 11. Trends were found between positive MTWA (n = 15) and male gender
      (p = 0.10), lower LVEF (p = 0.10), and higher LVEDV (p = 0.09). In both
      subgroups, the presence, transmurality or extent of scar was not related to MTWA
      (all p > 0.45). In this small study, neither in patients with ICM or DCM a
      relation was found between the occurrence of MTWA and the presence, transmurality
      or extent of myocardial scar. Overall there was a significant relation between
      heart failure remodeling parameters and positive MTWA. 

PMID- 24563011
TI  - Electronic excitations in Guanine quadruplexes.
AB  - Guanine rich DNA strands, such as those encountered at the extremities of human
      chromosomes, have the ability to form four-stranded structures (G-quadruplexes)
      whose building blocks are guanine tetrads. G-quadruplex structures are
      intensively studied in respect of their biological role, as targets for
      anticancer therapy and, more recently, of their potential applications in the
      field of molecular electronics. Here we focus on their electronic excited states
      which are compared to those of non-interacting mono-nucleotides and those of
      single and double stranded structures. Particular emphasis is given to excited
      state relaxation processes studied by time-resolved fluorescence spectroscopy
      from femtosecond to nanosecond time scales. They include ultrafast energy
      transfer and trapping of pipi* excitations by charge transfer states. The effect
      of various structural parameters, such as the nature of the metal cations located
      in the central cavity of G-quadruplexes, the number of tetrads or the
      conformation of the constitutive single strands, are examined. 

PMID- 24563012
TI  - Arrays of dipolar molecular rotors in Tris(o-phenylenedioxy) cyclotriphosphazene.
AB  - Regular two-dimensional or three-dimensional arrays of mutually interacting
      dipolar molecular rotors represent a worthy synthetic objective. Their dielectric
      properties, including possible collective behavior, will be a sensitive function
      of the location of the rotors, the orientation of their axes, and the size of
      their dipoles. Host-guest chemistry is one possible approach to gaining fine
      control over these factors. We describe the progress that has been achieved in
      recent years using tris (o-phenylenedioxy)cyclotriphosphazene as a host and a
      series of rod-shaped dipolar molecular rotors as guests. Structures of both
      surface and bulk inclusion compounds have been established primarily by solid
      state nuclear magnetic resonance (NMR) and powder X-ray diffraction (XRD)
      techniques. Low-temperature dielectric spectroscopy revealed rotational barriers
      as low as 1.5 kcal/mol, but no definitive evidence for collective behavior has
      been obtained so far.

PMID- 24563013
TI  - Transition-metal-complexed catenanes and rotaxanes: from dynamic systems to
      functional molecular machines.
AB  - Transition metal-based catenanes and rotaxanes constitute a specific class of
      mechanically interlocked molecules whose metal centers are essential both as
      templates in the construction of the compounds and for their ability to induce
      large-amplitude motions. In the present chapter we will first present a
      historical perspective of the field of interlocking compounds in general, in
      relation to molecular machines, starting with old work dating back to the 1980s
      and 1990s. Copper was shown many years ago to be the metal of choice for
      synthesizing the compounds via a template approach and for setting the molecules
      in motion using a redox signal (Cu(II)/Cu(I)). In a second paragraph, we will
      discuss various rotaxanes able to undergo a pirouetting motion of the axis within
      the threaded ring. Two families of such molecules will be mentioned: (1) a
      porphyrin-containing [2]rotaxane whose pirouetting motion is induced by a
      chemical reaction and (2) electrochemically driven systems. In this second
      category of [2]rotaxanes, the rate of motion could be dramatically increased by
      gradually modifying structural parameters and, in particular, by making the metal
      center less and less hindered by its surrounding ligands. The third section will
      be devoted to molecular shuttles and muscles, both families of compounds being
      reminiscent of linear machines such as biological muscles. By replacing the
      classical 2,9-diaryl-1,10-phenanthroline chelate (highly shielding and hindering)
      used by our group since the 1980s by an endocyclic but non-sterically hindering
      3,3'-biisoquinoline derivative, the shuttling rate was increased in spectacular
      fashion, demonstrating the importance of steric factors in transition metal-based
      molecular machines. The same 3,3'-biisoquinoline motif was also used in the
      elaboration of a three-station shuttle, leading to long-distance (>20 A)
      transport of a ring along the axis on which it is threaded. Finally, porphyrin
      containing [3]rotaxanes and [4]rotaxanes, the latter displaying an overall cyclic
      structure, will be discussed and shown to behave as adjustable and switchable
      receptors. The synthesis of such compounds is a particularly challenging task in
      itself. In addition, the new receptors display fascinating properties such as, in
      particular, their ability to compress various guests and to expel them from their
      binding site using a chemical signal. 

PMID- 24563014
TI  - Novel estradiol analogue induces apoptosis and autophagy in esophageal carcinoma
      cells.
AB  - Cancer is the second leading cause of death in South Africa. The critical role
      that microtubules play in cell division makes them an ideal target for the
      development of chemotherapeutic drugs that prevent the hyperproliferation of
      cancer cells. The new in silico-designed estradiol analogue 2-ethyl-3-O
      sulfamoylestra-1,3,5(10)16-tetraene (ESE-16) was investigated in terms of its in
      vitro antiproliferative effects on the esophageal carcinoma SNO cell line at a
      concentration of 0.18 MUM and an exposure time of 24 h. Polarization-optical
      differential interference contrast and triple fluorescent staining (propidium
      iodide, Hoechst 33342 and acridine orange) revealed a decrease in cell density,
      metaphase arrest, and the occurrence of apoptotic bodies in the ESE-16-treated
      cells when compared to relevant controls. Treated cells also showed an increase
      in the presence of acidic vacuoles and lysosomes, suggesting the occurrence of
      autophagic processes. Cell death via autophagy was confirmed using the Cyto-ID
      autophagy detection kit and the aggresome detection assay. Results showed an
      increase in autophagic vacuole and aggresome formation in ESE-16 treated cells,
      confirming the induction of cell death via autophagy. Cell cycle progression
      demonstrated an increase in the sub-G1 fraction (indicative of the presence of
      apoptosis). In addition, a reduction in mitochondrial membrane potential was also
      observed, which suggests the involvement of apoptotic cell death induced by ESE
      16 via the intrinsic apoptotic pathway. In this study, it was demonstrated that
      ESE-16 induces cell death via both autophagy and apoptosis in esophageal
      carcinoma cells. This study paves the way for future investigation into the role
      of ESE-16 in ex vivo and in vivo studies as a possible anticancer agent.

PMID- 24563015
TI  - Pleasure boatyard soils are often highly contaminated.
AB  - The contamination in pleasure boatyards has been investigated. Measured
      concentrations of copper, zinc, lead, mercury, cadmium, tributyltin (TBT), the 16
      most common polycyclic aromatic hydrocarbons (?16 PAHs), and the seven most
      common polychlorinated biphenyls (?7 PCBs) from investigations at 34 boatyards
      along the Swedish coast have been compiled. The maximum concentrations were 7,700
      for Cu, 10,200, for Zn, 40,100 for Pb, 188 for Hg, 18 for Cd, 107 for TBT, 630
      for carcinogenic PAHs, 1,480 for ?16 PAHs, and 3.8 mg/kg DW for ?7 PCB; all 10
      2,000 higher than the Swedish environmental qualitative guidelines. In addition,
      the mean of the median values found at the 34 places shows that the lower
      guidance value for sensitive use of land was exceeded for the ?7 PCBs,
      carcinogenic PAHs, TBT, Pb, Hg, and Cu by a factor of 380, 6.8, 3.6, 2.9, 2.2 and
      1.7, respectively. The even higher guideline value for industrial use was
      exceeded for the ?7 PCBs and TBT by a factor of 15 and 1.8, respectively. TBT,
      PAHs, Pb, Cd, and Hg are prioritized substances in the European Water Framework
      Directive and should be phased out as quickly as possible. Because of the risk of
      leakage from boatyards, precautions should be taken. The high concentrations
      measured are considered to be dangerous for the environment and human health and
      highlight the urgent need for developing and enforcing pleasure boat maintenance
      guidelines to minimize further soil and nearby water contamination. 

PMID- 24563017
TI  - Comparison of glucose variability assessed by a continuous glucose-monitoring
      system in patients with type 2 diabetes mellitus switched from NPH insulin to
      insulin glargine: the COBIN2 study.
AB  - BACKGROUND: Glucose variability combined with glycosylated hemoglobin (HbA1c)
      assessments more reliably represents the level of glycemic control. The study was
      aimed to compare blood glucose variability with insulin glargine vs. neutral
      protamine Hagedorn (NPH) in patients with type 2 diabetes mellitus using a
      continuous glucose-monitoring system (CGMS), in patients treated with basal
      insulin using stable dose of oral antidiabetic agents and HbA1c in the range of
      4.5-8.0 % International Federation of Clinical Chemistry (IFCC) units. [6.2-9.4 %
      Diabetes Control and Complications Trial (DCCT) units]. METHODS: This was a
      multicenter, prospective, open-label, single-arm study in patients (N = 116)
      treated for >= 2 months with NPH and metformin combined with sulfonylurea or
      glinide. Glucose variability was measured after a 4-week NPH treatment phase and
      after a subsequent 12-week glargine treatment phase using CGMS. Based on 72-hour
      CGMS, glucose variability was assessed by area under the curve [AUC (mmol/L .
      h)]. Differences (glargine-NPH) in AUC within 24 h in the glucose ranges of <=
      3.3, <= 3.9, 7.5-3.9 (margins excluding), >= 7.5, >= 10, and >= 15 mmol/L were
      evaluated. Circadian fluctuation of glucose was assessed by M-value (log
      transformation of the deviation from an arbitrary standard). RESULTS: AUCs of
      glucose in the lowest ranges (<= 3.3 and <= 3.9 mmol/L) did not change
      significantly after treatment with glargine. Those in the higher ranges (>= 7.5,
      >= 10, and >= 15 mmol/L) were significantly lower (p < 0.001 for all ranges),
      whereas AUC of glucose in the normal range (3.9-7.5 mmol/L) was significantly
      higher (p < 0.001) at the end of glargine treatment phase. Circadian fluctuation
      of glucose assessed by M-value showed a significant decrease after glargine
      treatment (p < 0.003). No significant differences in hypoglycemia confirmed by
      glucose value <= 3.3 mmol/L were found between treatment phases. This trial is
      registered at ClinicalTrials.gov, NCT00659477. CONCLUSIONS: As monitored by CGMS,
      switching from NPH to glargine with active titration shifted glucose from
      abnormally high to normal levels with reduced fluctuation and without increased
      risk of hypoglycemia.

PMID- 24563018
TI  - Vascular neural network: the importance of vein drainage in stroke.
AB  - This perspective commentary summarized the stroke pathophysiology evolution,
      especially the focus in the past on neuroprotection and neurovascular protection
      and highlighted the newer term for stroke pathophysiology: vascular neural
      network. Emphasis is on the role of venules and veins after an acute stroke and
      as potential treatment targets. Vein drainage may contribute to the acute phase
      of brain edema and the outcomes of stroke patients. 

PMID- 24563020
TI  - Establishing hospital admission criteria of pediatric Henoch-Schonlein purpura.
AB  - The current study aimed to define evidence-based admission criteria of pediatric
      Henoch-Schonlein purpura (HSP). In addition, we aimed to better characterize
      epidemiological and clinical features of pediatric HSP in Israel. We performed a
      retrospective cohort study of all children with HSP admitted during a 15 years
      period to a single pediatric department. We strictly collected the clinical data
      of all HSP cases. Each case was categorized as either "necessary admission" or
      "unnecessary admission." We compared the two groups, using initially Chi square
      (chi(2)) and student "t" tests, and thereafter, we employed logistic stepwise
      regression analysis. One hundred and sixty-three children with HSP were included.
      A set of six clinical criteria of which the presence of minimum one predicts the
      need for hospitalization were identified including: orchitis, moderate or severe
      abdominal pain, arthritis involving more than two joints, proteinuria, clear
      evidence of gastrointestinal bleeding, and inability to ambulate. In conclusion,
      we suggest a predictive model for the admission of pediatric patients with acute
      HSP. The implementation of this model can significantly reduce unnecessary
      admissions.

PMID- 24563021
TI  - A new protocol for the analysis of pharmaceuticals, pesticides, and hormones in
      sediments and suspended particulate matter from rivers and municipal wastewaters.
AB  - We developed a protocol to quantify 12 emerging contaminants (ECs)
      (pharmaceuticals and hormones) and pesticides extracted from suspended
      particulate matter (SPM) of river water and municipal wastewaters samples as well
      as river sediments. The separation of suspended solids was realized using
      filtration of water samples. We tested a series of six different filter types.
      The effect of filtration on the concentrations of dissolved contaminants was
      evaluated to minimize losses of target compounds. The river sediment samples were
      lyophilized, and both SPM and sediment samples were subjected to ultrasonic
      extraction combined with C18 cartridge clean-up. Quantifications were realized
      using mass spectrometry. The method recoveries of all compounds ranged from 38 to
      112 % in all studied matrices; poorer recoveries were achieved for
      sulfamethoxazole and diclofenac (as low as 38 %), whereas the recoveries for all
      other compounds in the wastewater treatment plant (WWTP) samples were between 68
      and 111 %. The detection limits in sediments and SPM from river samples for the
      12 analytes varied from 0.7 to 9.4 ng g(-1) and from 21 to 92 ng g(-1) for WWTP
      SPM samples. All targeted ECs were detected with concentrations ranging from 3 to
      5,440 ng g(-1) in the studied matrices with the highest concentrations observed
      in WWTP SPM samples. A significant portion of the contaminants in a water sample
      is clearly associated with the suspended particulates. Optimization of water
      treatment processes and environmental fate must absolutely consider the fraction
      of contaminants that is particulate-bound if one hopes to have a reasonable mass
      balance.

PMID- 24563019
TI  - Increased substance P expression in the trochanteric bursa of patients with
      greater trochanteric pain syndrome.
AB  - Greater trochanteric pain syndrome (GTPS) is a pathology that can involve the
      trochanteric bursa or the tendons which attach to the greater trochanter. To
      clarify the potential importance of bursa versus tendon pathology and of
      substance P (SP) in contributing to pain in this condition tendon and bursa
      tissue biopsies were obtained from 34 patients with GTPS and 29 control subjects.
      Specimens were evaluated via light microscopy for histopathological and
      morphological differences, as well as using immunohistochemistry for macrophages
      (CD68), inflammatory cells (CD45) and SP. Bursa [stroma score, mean (SD): 4.18
      (1.65) vs. 2.53 (1.61), p = 0.051] and tendon [Bonar score, mean (SD): GTPS mean
      (SD) 12.65 (2.0), control (10.43 (4.84), p = 0.04] from subjects with GTPS
      demonstrated more extensive signs of pathology than specimens from control
      subjects. There was a significantly greater presence of SP in the bursa
      (frequency: 9/12 vs. 6/16, p = 0.047), but not in the tendon (8/12 vs. 8/15, p =
      0.484) of subjects with GTPS compared to controls. An increased presence of SP in
      the trochanteric bursa may be related to the pain associated with GTPS.

PMID- 24563022
TI  - Penicillium verruculosum SG: a source of polyketide and bioactive compounds with
      varying cytotoxic activities against normal and cancer lines.
AB  - A newly isolated fungus Penicillium verruculosum SG was evaluated for the
      production and characterization of bioactive colored secondary metabolites using
      solid-state fermentation along with their cytotoxic activities against normal and
      cancer cell lines. Logical fragmentation pattern following column chromatography,
      thin layer chromatography and liquid chromatography and mass spectrometry of
      crude culture filtrate of fungus revealed the presence of different polyketide
      pigments and other bioactive compounds. Cytotoxicity of the selected colored
      fractions of fungal filtrate containing different compounds revealed IC50
      (MUg/ml) values ranging from 5 to 100. It was significantly higher in case of
      orevactaene (5 + 0.44) and monascorubrine followed by pyripyropene (8 + 0.63)
      against cancer cell line KA3IT. Overall, these compounds considerably showed less
      toxicity toward normal cell lines NIH3T3, HSCT6, HEK293 and MDCK. XRD of a yellow
      crystalline compound (224.21 m/z) confirmed its 3-dimensional structure as
      phenazine 1 carboxylic acid (C13H8N2O2) (broad spectrum antibiotic), and it is
      first time reported in fungi. 

PMID- 24563024
TI  - Angiolipoma of the sellar region.

PMID- 24563025
TI  - Author reply: To PMID 23444421.

PMID- 24563023
TI  - Oligodendroglia in cortical multiple sclerosis lesions decrease with disease
      progression, but regenerate after repeated experimental demyelination.
AB  - Cerebral cortex shows a high endogenous propensity for remyelination. Yet,
      widespread subpial cortical demyelination (SCD) is a common feature in
      progressive multiple sclerosis (MS) and can already be found in early MS. In the
      present study, we compared oligodendroglial loss in SCD in early and chronic MS.
      Furthermore, we addressed in an experimental model whether repeated episodes of
      inflammatory SCD could alter oligodendroglial repopulation and subsequently lead
      to persistently demyelinated cortical lesions. NogoA(+) mature oligodendrocytes
      and Olig2(+) oligodendrocyte precursor cells were examined in SCD in patients
      with early and chronic MS, normal-appearing MS cortex, and control cortex as well
      as in the rat model of repeated targeted cortical experimental autoimmune
      encephalomyelitis (EAE). NogoA(+) and Olig2(+) cells were significantly reduced
      in SCD in patients with chronic, but not early MS. Repeated induction of SCD in
      rats resulted only in a transient loss of NogoA(+), but not Olig2(+) cells during
      the demyelination phase. This phase was followed by complete oligodendroglial
      repopulation and remyelination, even after four episodes of demyelination. Our
      data indicate efficient oligodendroglial repopulation in subpial cortical lesions
      in rats after repeated SCD that was similar to early, but not chronic MS cases.
      Accordingly, four cycles of experimental de- and remyelination were not
      sufficient to induce sustained remyelination failure as found in chronic cortical
      MS lesions. This suggests that alternative mechanisms contribute to
      oligodendrocyte depletion in chronic cortical demyelination in MS. 

PMID- 24563026
TI  - Electrochemical mineral scale prevention and removal on electrically conducting
      carbon nanotube--polyamide reverse osmosis membranes.
AB  - The electrochemical prevention and removal of CaSO4 and CaCO3 mineral scales on
      electrically conducting carbon nanotube - polyamide reverse osmosis membrane was
      investigated. Different electrical potentials were applied to the membrane
      surface while filtering model scaling solutions with high saturation indices.
      Scaling progression was monitored through flux measurements. CaCO3 scale was
      efficiently removed from the membrane surface through the intermittent
      application of a 2.5 V potential to the membrane surface, when the membrane acted
      as an anode. Water oxidation at the anode, which led to proton formation,
      resulted in the dissolution of deposited CaCO3 crystals. CaSO4 scale formation
      was significantly retarded through the continuous application of 1.5 V DC to the
      membrane surface, when the membrane was operated as an anode. The continuous
      application of a sufficient electrical potential to the membrane surface leads to
      the formation of a thick layer of counter-ions along the membrane surface that
      pushed CaSO4 crystal formation away from the membrane surface, allowing the
      formed crystals to be carried away by the cross-flow. We developed a simple
      model, based on a modified Poisson-Boltzmann equation, which qualitatively
      explained our observed experimental results. 

PMID- 24563027
TI  - Cost analysis of a novel interdisciplinary model for advanced illness management.
AB  - PURPOSE: This research project evaluated cost outcomes for patients in the @HOMe
      Support program, a novel interdisciplinary home-based program for patients and
      caregivers facing advanced illness drawing on the Chronic Care Model. METHODS:
      Cost analysis involved paired sample t-tests to examine pre-post differences in
      health care expenditures obtained from Health Maintenance Organization (HMO)
      claims data for program participants. RESULTS: Average 6-month costs per month
      significantly declined for patients older than 65 years of age from 1 HMO
      (US$9300-US$5900, P = .001). Evaluation of the second HMO showed that patients
      less than 65 years of age with lower preentry costs (<70 000) had a
      nonsignificant decline in total costs (US$18 787-US$13 781, P = .08).
      CONCLUSIONS: Study findings suggest @HOMe Support is associated with reductions
      in the use and cost for most health services over time.

PMID- 24563028
TI  - A study of Canadian hospice palliative care volunteers' attitudes toward
      physician-assisted suicide.
AB  - The purpose of this study was to examine the attitudes of hospice palliative care
      (HPC) volunteers who provide in-home support (n = 47) and members of the
      community (n = 58) toward the issue of physician-assisted suicide (PAS). On the
      first part of the survey, participants responded to 15 items designed to assess
      their attitudes toward PAS. An examination of individual items revealed
      differences in opinions among members of both the groups. Responses to additional
      questions revealed that the majority of volunteers and community members (1)
      support legalizing PAS; (2) would choose HPC over PAS for themselves if they were
      terminally ill; and (3) think Canadians should place more priority on developing
      HPC rather than on legalizing PAS. The implications of these findings are
      discussed.

PMID- 24563029
TI  - Chitosan-Zn chelate increases antioxidant enzyme activity and improves immune
      function in weaned piglets.
AB  - This experiment was performed in order to investigate the effects of chitosan-Zn
      chelate (CS-Zn) on activities of antioxidant enzymes and immune function in
      weaned piglets. One hundred and twenty weaned piglets (Duroc * Landrace *
      Yorkshire) with 7.12 +/- 0.25 kg body weight were allotted to four treatments. A
      basal diet without Zn supplementation was used as control group. The other three
      treatments were fed the control diet supplemented with 100 mg/kg Zn as ZnSO4, 100
      mg/kg Zn as CS-Zn, 100 mg/kg Zn as ZnSO4 and chitosan (the content of chitosan
      was the same as that of CS-Zn), respectively. The feeding trial lasted 30 days.
      Spleen index of pigs fed dietary CS-Zn was higher (p < 0.05) than that of control
      pigs. Thymus index and lymph node index did not differ among the pigs fed any
      diets (p > 0.05). T-AOC levels, Cu-ZnSOD, and GSH-PX activities in serum or liver
      of the pigs receiving CS-Zn diet were higher than those of the pigs fed CS+ZnSO4
      or ZnSO4 diets (p < 0.05). These pigs fed dietary CS-Zn also showed lower MDA
      content in liver compared with the pigs fed other diets (p < 0.05). Serum IgA,
      complement 3, and complement 4 levels of pig fed dietary CS-Zn was higher than
      those of the pigs fed other diets (p < 0.05). Supplemental dietary Zn did not
      change serum IgG and IgM levels (p > 0.05). The ALP activity of pigs fed dietary
      CS-Zn was higher than those of the pigs fed other three diets (p < 0.05). No
      significant differences were founded in serum GOT or GPT activities of pigs fed
      dietary Zn (p > 0.05). The results of the present study indicated that chitosan
      Zn chelate could increase antioxidant capacity and improve immune function in
      weaned piglets compared with ZnSO4 or chitosan.

PMID- 24563030
TI  - Purification of Holstein bull semen paraoxonase 1 (PON1) by hydrophobic
      interaction chromatography and investigation of its inhibition kinetics by heavy
      metals.
AB  - In this study, paraoxonase 1 (PON1; EC 3.1.8.1) was purified from bull semen, and
      some characteristics of the enzyme were investigated. In vitro inhibition effect
      of some heavy metals, including Cu(2+), Mn(2+), Cd(2+), Zn(2+), Ni(2+), and
      Pb(2+), on the activity of the purified enzyme was also investigated. The
      purification of bull semen PON1 procedure was composed of two steps: ammonium
      sulfate precipitation and Sepharose-4B-L-tyrosine-1-naphthylamine hydrophobic
      interaction chromatography. The enzyme, having a specific activity of 288 EU/mg
      proteins, was purified 22.67-fold with a yield of 89 %. Sodium dodecyl sulfate
      (SDS)-polyacrylamide gel electrophoresis of the purified enzyme showed the
      presence of a single band with an apparent MW of 66 kDa. The V max and K M values
      for the paraoxon substrate were determined as 100 EU and 8.0 * 10(-5) M,
      respectively. The inhibitory effects of different heavy metals on PON1 activity
      were determined by using the paraoxon as a substrate. The results showed that all
      the metals, except for Cd(2+), inhibited the PON1 enzyme activity in a
      concentration-dependent fashion. IC50 values of Cu(2+), Mn(2+), Zn(2+), Ni(2+),
      and Pb(2+) were found as 2.59 * 10(-3), 1.17 * 10(-3), 42.74 * 10(-3), 99.10 *
      10(-3), 48.80 * 10(-3) mM, respectively. Conversely, Cd(2+) increased the bull
      semen PON1 enzyme activity. The present study has demonstrated that Cu(2+),
      Mn(2+), Zn(2+), Ni(2+), and Pb(2+) are serious toxic metals, which are able to
      increase the risk of oxidative stress development and a subsequent decrease of
      semen quality.

PMID- 24563031
TI  - Effects of antimony and arsenic on antioxidant enzyme activities of two steppic
      plant species in an old antimony mining area.
AB  - The present work was undertaken to determine strategies and antioxidant enzyme
      activities involved in the adaptation of two wild steppic plants (Hedysarum
      pallidum Desf. and Lygeum spartum L.) to the toxic environment of the abandoned
      antimony mining area of Djebel Hamimat (Algeria). For this purpose, soils and
      plants were collected in different zones coinciding with a Sb and As
      concentrations gradient in the soil. Antimony (Sb) and arsenic (As) were analyzed
      by ICP-OES in the soils and the aboveground parts and roots of the plants.
      Malondialdehyde (MDA) and antioxidant enzyme activities were measured by
      spectrometry. Results show levels of Sb and As exceptionally high in most soil
      and plant samples. The two species accumulate differently Sb and As in their
      above and belowground parts. MDA levels, in the two parts of both species,
      increase significantly with increasing soil Sb and As concentrations, but they
      are significantly higher in H. pallidum than in L. spartum. The activities of
      antioxidant enzymes differ significantly according to the soil metalloid
      concentrations, the plant species considered and the plant part. Apart from
      superoxide dismutase (SOD) whose activity is, overall, higher in H. pallidum than
      in L. spartum, the activities of all the other enzymes studied (glutathione S
      transferase (GST), catalase (CAT), peroxidase (POD), and ascorbate peroxidase
      (APX)) are generally higher in L. spartum than in H. pallidum. For both species,
      APX and GST are overall more active in the upper parts than in the roots, while
      it is the reverse for SOD and CAT. POD is more active in the upper parts than in
      the roots of L. spartum and the reverse applies to H. pallidum. It appears that
      the two studied plant species use different tolerance strategies to protect
      themselves against elevated As and Sb concentrations.

PMID- 24563033
TI  - The C-terminal part of microcin B is crucial for DNA gyrase inhibition and
      antibiotic uptake by sensitive cells.
AB  - Microcin B (McB) is a ribosomally synthesized antibacterial peptide. It contains
      up to nine oxazole and thiazole heterocycles that are introduced
      posttranslationally and are required for activity. McB inhibits the DNA gyrase, a
      validated drug target. Previous structure-activity analyses indicated that two
      fused heterocycles located in the central part of McB are important for
      antibacterial action and gyrase inhibition. Here, we used site-specific
      mutagenesis of the McB precursor gene to assess the functional significance of
      the C-terminal part of McB that is located past the second fused heterocycle and
      contains two single heterocycles as well as an unmodified four-amino-acid C
      terminal tail. We found that removal of unmodified C-terminal amino acids of McB,
      while having no effect on fused heterocycles, has a very strong negative effect
      on activity in vivo and in vitro. In fact, even nonconservative point
      substitutions in the last McB amino acid have a very strong effect by
      simultaneously decreasing uptake and ability to inhibit the gyrase. The results
      highlight the importance of unmodified McB amino acids for function and open the
      way for creation of recombinant McB derivatives with an altered or expanded
      spectrum of antibacterial action. 

PMID- 24563032
TI  - The PhoU protein from Escherichia coli interacts with PhoR, PstB, and metals to
      form a phosphate-signaling complex at the membrane.
AB  - Robust growth in many bacteria is dependent upon proper regulation of the
      adaptive response to phosphate (Pi) limitation. This response enables cells to
      acquire Pi with high affinity and utilize alternate phosphorous sources. The
      molecular mechanisms of Pi signal transduction are not completely understood.
      PhoU, along with the high-affinity, Pi-specific ATP-binding cassette transporter
      PstSCAB and the two-component proteins PhoR and PhoB, is absolutely required for
      Pi signaling in Escherichia coli. Little is known about the role of PhoU and its
      function in regulation. We have demonstrated using bacterial two-hybrid analysis
      and confirmatory coelution experiments that PhoU interacts with PhoR through its
      PAS (Per-ARNT-Sim) domain and that it also interacts with PstB, the cytoplasmic
      component of the transporter. We have also shown that the soluble form of PhoU is
      a dimer that binds manganese and magnesium. Alteration of highly conserved
      residues in PhoU by site-directed mutagenesis shows that these sites play a role
      in binding metals. Analysis of these phoU mutants suggests that metal binding may
      be important for PhoU membrane interactions. Taken together, these results
      support the hypothesis that PhoU is involved in the formation of a signaling
      complex at the cytoplasmic membrane that responds to environmental Pi levels. 

PMID- 24563034
TI  - Analysis of the loss in heat and acid resistance during germination of spores of
      Bacillus species.
AB  - A major event in the nutrient germination of spores of Bacillus species is
      release of the spores' large depot of dipicolinic acid (DPA). This event is
      preceded by both commitment, in which spores continue through germination even if
      germinants are removed, and loss of spore heat resistance. The latter event is
      puzzling, since spore heat resistance is due largely to core water content, which
      does not change until DPA is released during germination. We now find that for
      spores of two Bacillus species, the early loss in heat resistance during
      germination is most likely due to release of committed spores' DPA at
      temperatures not lethal for dormant spores. Loss in spore acid resistance during
      germination also paralleled commitment and was also associated with the release
      of DPA from committed spores at acid concentrations not lethal for dormant
      spores. These observations plus previous findings that DPA release during
      germination is preceded by a significant release of spore core cations suggest
      that there is a significant change in spore inner membrane permeability at
      commitment. Presumably, this altered membrane cannot retain DPA during heat or
      acid treatments innocuous for dormant spores, resulting in DPA-less spores that
      are rapidly killed. 

PMID- 24563036
TI  - The flagellar soluble protein FliK determines the minimal length of the hook in
      Salmonella enterica serovar Typhimurium.
AB  - The length of the flagellar hook is controlled by the soluble protein FliK. FliK
      is structurally divided into two halves with distinct functions; the N-terminal
      half determines hook length, while the C-terminal half switches the secretion
      substrate specificity, consequently terminating hook elongation. FliK properly
      achieves both functions only when it is secreted. In a previous paper, we showed
      that a temperature-sensitive flgE mutant of Salmonella enterica serovar
      Typhimurium, SJW2219, produced basal bodies with short hooks (average length, 25
      nm) at 37 degrees C. In this study, we show that the mutant cells grown at 37
      degrees C secrete FliK but not flagellin (FliC), indicating that FliK is
      abortively secreted into the medium when the hook is shorter than 30 nm. In
      contrast, FliK unfailingly switches the gate modes when the hook is longer than
      30 nm. Taking the FliC, FliK, and FlgM secretion patterns into account, we
      conclude that FliK determines the minimal length of the hook. We will discuss how
      FliK detects the critical switching point of the secretion gate. 

PMID- 24563039
TI  - Personality and the response to predation risk: effects of information quantity
      and quality.
AB  - Within aquatic ecosystems, chemosensory cues provide valuable public information
      regarding the form and degree of risk, allowing prey to make informed behavioural
      decisions. Such cues, however, may vary in both relative concentration detected
      (i.e. 'quantity') and reliability of the information available (i.e. 'quality'),
      leading to varying response patterns. Moreover, prey species are also known to
      exhibit consistent behavioural tactics towards managing risk (i.e. personality),
      possibly shaping their use of public information. Here, we present two
      experiments examining the potential interacting effects of personality and the
      quantity (Experiment 1) or quality (Experiment 2) of public information on the
      short-term predator avoidance responses of wild-caught Trinidadian guppies under
      semi-natural conditions. Our first experiment demonstrated that personality
      shaped responses to a high concentration of alarm cues (high risk), with shyer
      guppies exhibiting stronger antipredator responses than bolder guppies. When
      exposed to either low risk or stream water controls, personality had no effect on
      the intensity of response. Our second experiment demonstrated that personality
      again shaped the response to high concentrations of alarm cues (a known risk) but
      not to a novel chemosensory cue (tilapia odour). When exposed to the unknown
      novel cue, guppies exhibited a relatively high intensity antipredator response,
      regardless of personality. Combined, our results suggest that individual risk
      taking tactics shape the use of public information in a context-dependent
      fashion. 

PMID- 24563035
TI  - Escherichia coli isolate for studying colonization of the mouse intestine and its
      application to two-component signaling knockouts.
AB  - The biology of Escherichia coli in its primary niche, the animal intestinal
      tract, is remarkably unexplored. Studies with the streptomycin-treated mouse
      model have produced important insights into the metabolic requirements for
      Escherichia coli to colonize mice. However, we still know relatively little about
      the physiology of this bacterium growing in the complex environment of an
      intestine that is permissive for the growth of competing flora. We have developed
      a system for studying colonization using an E. coli strain, MP1, isolated from a
      mouse. MP1 is genetically tractable and does not require continuous antibiotic
      treatment for stable colonization. As an application of this system, we
      separately knocked out each two-component system response regulator in MP1 and
      performed competitions against the wild-type strain. We found that only three
      response regulators, ArcA, CpxR, and RcsB, produce strong colonization defects,
      suggesting that in addition to anaerobiosis, adaptation to cell envelope stress
      is a critical requirement for E. coli colonization of the mouse intestine. We
      also show that the response regulator OmpR, which had previously been
      hypothesized to be important for adaptation between in vivo and ex vivo
      environments, is not required for MP1 colonization due to the presence of a third
      major porin. 

PMID- 24563037
TI  - The K(C) channel in the cbb3-type respiratory oxygen reductase from Rhodobacter
      capsulatus is required for both chemical and pumped protons.
AB  - The heme-copper superfamily of proton-pumping respiratory oxygen reductases are
      classified into three families (A, B, and C families) based on structural and
      phylogenetic analyses. Most studies have focused on the A family, which includes
      the eukaryotic mitochondrial cytochrome c oxidase as well as many bacterial
      homologues. Members of the C family, also called the cbb3-type oxygen reductases,
      are found only in prokaryotes and are of particular interest because of their
      presence in a number of human pathogens. All of the heme-copper oxygen reductases
      require proton-conducting channels to convey chemical protons to the active site
      for water formation and to convey pumped protons across the membrane. Previous
      work indicated that there is only one proton-conducting input channel (the K(C)
      channel) present in the cbb3-type oxygen reductases, which, if correct, must be
      utilized by both chemical protons and pumped protons. In this work, the effects
      of mutations in the K(C) channel of the cbb3-type oxygen reductase from
      Rhodobacter capsulatus were investigated by expressing the mutants in a strain
      lacking other respiratory oxygen reductases. Proton pumping was evaluated by
      using intact cells, and catalytic oxygen reductase activity was measured in
      isolated membranes. Two mutations, N346M and Y374F, severely reduced catalytic
      activity, presumably by blocking the chemical protons required at the active
      site. One mutation, T272A, resulted in a substantially lower proton-pumping
      stoichiometry but did not inhibit oxygen reductase activity. These are the first
      experimental data in support of the postulate that pumped protons are taken up
      from the bacterial cytoplasm through the K(C) channel.

PMID- 24563040
TI  - Complications of the 'Enhanced Recovery after Surgery Programme' following
      pedicled vertical rectus abdominis myocutaneous flap in perineum reconstruction.
AB  - The enhanced recovery programme, pioneered in the colorectal surgical setting,
      aims to reduce the length of inpatient stay following a procedure and was started
      in our trust in 2006. We present the case of a patient who underwent perineal
      reconstruction with a pedicled vertical rectus abdominis myocutaneous (VRAM) who
      subsequently developed bladder outflow obstruction compromising flap viability.
      As a result of our experience we are in the process of producing new guidelines
      that advocate patients undergoing a VRAM flap for perineal reconstruction should
      be exempt from aspects of the enhanced recovery programme, in particular early
      removal of the catheter should be avoided. 

PMID- 24563041
TI  - Aneurysmal bone cyst of medial cuneiform and a novel surgical technique for mid
      foot reconstruction.
AB  - Aneurysmal bone cyst of the foot is extremely rare and the involvement of medial
      cuneiform has never been reported in the literature. In this report, we describe
      a 15-year-old boy who presented with a 6-month history of pain and swelling in
      his left foot. Radiograph demonstrated a lytic lesion in the medial cuneiform
      extending on to the middle cuneiform, the navicular bone and the base of the
      first metatarsal. En bloc resection of the lesion was performed using a dorsal
      longitudinal incision along the first ray. Tricortical iliac crest graft was
      harvested and shaped to fill the defect. Two drill holes were made and the
      tibialis anterior tendon was attached to the graft. Prepared, morcellised
      allograft was placed along the junction of autograft and host bone. At 1-year
      follow-up, the patient was pain free, the medial arch of the foot was maintained
      and the graft had united with the host bone. 

PMID- 24563042
TI  - A solitary osteochondroma of the scapula.

PMID- 24563043
TI  - Severe vascular calcification and gangrene in a haemodialysis patient.

PMID- 24563044
TI  - Neck of femur fracture fixation in a bilateral amputee: an uncommon condition
      requiring an improvised fracture table positioning technique.
AB  - While neck of femur fractures are common it is rare to see this injury in a
      bilateral leg amputee. Special consideration needs to be given to the management
      of these patients. We report the case of a 58-year-old man with bilateral leg
      amputation who presented to the emergency department with left hip pain following
      a fall. A fracture of the left neck of femur with extension into the femoral
      shaft was diagnosed. Internal fixation was planned with a dynamic hip screw.
      Standard fracture table setup, which allows for traction of the fractured limb
      and positioning of the contralateral limb such that anteroposterior and lateral X
      rays can be obtained, was not possible in this case due to the amputations. We
      highlight considerations that need to be made in positioning a bilateral amputee
      for neck of femur fracture fixation and also highlight an improvised technique
      that can be utilised by other surgeons. 

PMID- 24563046
TI  - Thank you for your contributions.

PMID- 24563045
TI  - Keeping track of migratory pulmonary lesions.
AB  - Tricuspid valve endocarditis (TVE) is rarely considered in the differential
      diagnosis of a febrile patient who does not use intravenous drugs.We describe the
      case of a 62-year-old male patient with a 3-month history of remittent fever and
      13% weight loss. The patient denied intravenous drugs use or recent invasive
      procedures. His medical history included type 2 diabetes, alcohol abuse and
      smoking. Clinical evaluation revealed systemic inflammatory syndrome with
      unremarkable physical examination. Ancillary tests showed leucocytosis,
      thrombocytopenia and elevated C reactive protein. Empiric intravenous ceftriaxone
      was started, but after an initial improvement, fever relapsed 2 days after
      stopping antibiotherapy. A CT scan showed multiple disseminated lesions,
      suggesting lung metastatic tumour. Further studies excluded malignancy and
      revealed TVE caused by Streptococcus bovis with pulmonary embolism. The aim of
      our study is to stress the importance of evoking TVE in the differential
      diagnosis of fever with lung manifestations, and to highlight the possible
      association between S bovis, colorectal cancer and liver disease. 

PMID- 24563047
TI  - Doctoral dental hygiene education: insights from a review of nursing literature
      and program websites.
AB  - PURPOSE: Because dental hygiene education has had a similar trajectory as nursing
      education, this critical review addressed the question "What can the dental
      hygiene discipline learn from the nursing experience in their development of
      doctoral education?" Information on admission and degree requirements, modes of
      instruction, and program length and cost was collected from the websites
      associated with 112 of 125 PhD nursing programs nationally, and 174 of 184 Doctor
      of Nursing Practice (DNP) programs. In addition, searches of PubMed, Cumulative
      Index Nursing Allied Health Literature (CINAHL) and the Web of Science were
      utilized to identify key articles and books. The following 4 insights relevant to
      future dental hygiene doctoral education emerged from a review of nursing
      doctoral education: First, nursing doctoral education offers 2 main doctoral
      degrees, the research-focused PhD degree and the practice-focused DNP degree.
      Second, there is a well-documented need for doctoral prepared nurses to teach in
      nursing programs at all levels in managing client-care settings. Third, curricula
      quality and consistency is a priority in nursing education. Fourth, there are
      numerous templates on nursing doctoral education available. The historical
      background of nursing doctoral education was also reviewed, with the assumption
      that it can be used to inform the dental hygiene discipline when establishing
      doctoral dental hygiene education. The authors recommend that with the current
      changes toward medically and socially compromised patient populations, impending
      changes in health care policies and the available critical mass of master degree
      prepared dental hygiene scholars ready to advance the discipline, now is the time
      for the dental hygiene discipline to establish doctoral education.

PMID- 24563048
TI  - Factors associated with clinical skill remediation in dental hygiene education
      programs.
AB  - PURPOSE: The purpose of this study was to examine the challenges related to
      formal clinical remediation in dental hygiene programs, which include timing of
      student identification, policy development, and the issues of methodology and
      scheduling. METHODS: A 23 item investigator-designed survey was electronically
      distributed to all 303 U.S. entry-level dental hygiene program directors. This
      questionnaire included 23 forced-choice questions with the options to add
      comments to 8 of the questions. A total of 111 surveys were returned yielding a
      response rate of 36%. Descriptive statistics and Chi-square analyses were
      utilized to analyze relationships between responses and the degree earned from
      the dental hygiene program. RESULTS: All schools reported having a remediation
      policy; however, 13.6% of the respondents revealed this information was not
      readily available to students. The majority of respondents (67.8%) reported
      identifying students with clinical deficiencies in the preclinical semester, and
      15.5% identified students in the second year, second clinical semester.
      Instrumentation technique was identified as the area in greatest need of
      remediation (81%), followed by critical thinking and problem solving skills
      (12%). Coordination of faculty and student schedules to conduct remediation was
      identified as one of the greatest challenges by respondents (25.2%). Results of
      this study suggest that challenges exist with the process of remediation. Some of
      these challenges include involving the student in remedial plan development, the
      academic consequences associated with remediation and scheduling time and space
      for remedial activities. CONCLUSION: These findings indicate that respondents are
      well aware of the need for remediation policies in dental hygiene programs. The
      point in time varies when students in need of remediation are identified.
      Therefore, further research needs to be conducted to determine the reasons for
      this difference. Some reasons may include inability to grasp the foundational
      skills and/or the complexity of advanced instrumentation in the second year.
      Also, it is suggested that investigation regarding methods used to address the
      challenge of faculty and student scheduling for remediation sessions would be
      useful.

PMID- 24563049
TI  - Evaluating meaningful learning using concept mapping in dental hygiene education:
      a pilot study.
AB  - PURPOSE: Concept mapping, as a teaching strategy, has been shown to promote
      critical thinking and problem solving in educational settings. Dental clinicians
      must distinguish between critical and irrelevant characteristics in the delivery
      of care, thus necessitating reasoning skills to do so. One of the aims of the
      American Dental Education Association Commission on Change and Innovation (ADEA
      CCI) is to identify deficiencies in curriculum which were meant to improve
      critical thinking and problem solving skills necessary in clinical practice. The
      purpose of this study was to compare 2 teaching strategies, traditional lecture
      and lecture supported by concept mapping exercises within collaborative working
      groups, to determine if there is a beneficial effect on meaningful learning.
      METHODS: For this pilot study, the study population consisted of students from 2
      geographically separated associate level dental hygiene programs in the
      southeastern U.S. A quasi-experimental control group pre- and post-test design
      was used. The degree of meaningful learning achieved by both programs was
      assessed by comparing pre- and post-test results. RESULTS: Both programs
      experienced a significant degree of meaningful learning from pre- to post-test.
      However, there was no statistically significant difference between the programs
      on the post-test. These results were in direct contrast to research in other
      disciplines on concept mapping and its effect on promoting meaningful learning.
      Further investigation into the study's outcome was obtained through a follow-up
      focus group. CONCLUSION: In spite of careful attention to methodology in the
      development of this research project, the focus group illuminated methodological
      failings that potentially impacted the outcome of the study. Recommendations are
      underscored for future conduct of educational research of this kind.

PMID- 24563050
TI  - Dental hygiene students' perceptions of distance learning: do they change over
      time?
AB  - PURPOSE: The University of Arkansas for Medical Sciences dental hygiene program
      established a distant site where the didactic curriculum was broadcast via
      interactive video from the main campus to the distant site, supplemented with on
      line learning via Blackboard. This study compared the perceptions of students
      towards distance learning as they progressed through the 21 month curriculum.
      Specifically, the study sought to answer the following questions: Is there a
      difference in the initial perceptions of students on the main campus and at the
      distant site toward distance learning? Do students' perceptions change over time
      with exposure to synchronous distance learning over the course of the curriculum?
      METHODS: All 39 subjects were women between the ages of 20 and 35 years. Of the
      39 subjects, 37 were Caucasian and 2 were African-American. A 15-question Likert
      scale survey was administered at 4 different periods during the 21 month program
      to compare changes in perceptions toward distance learning as students progressed
      through the program. An independent sample t-test and ANOVA were utilized for
      statistical analysis. RESULTS: At the beginning of the program, independent
      samples t-test revealed that students at the main campus (n=34) perceived
      statistically significantly higher effectiveness of distance learning than
      students at the distant site (n=5). Repeated measures of ANOVA revealed that
      perceptions of students at the main campus on effectiveness and advantages of
      distance learning statistically significantly decreased whereas perceptions of
      students at distant site statistically significantly increased over time.
      Distance learning in the dental hygiene program was discussed, and replication of
      the study with larger samples of students was recommended.

PMID- 24563051
TI  - Musculoskeletal disorders in a 3 year longitudinal cohort of dental hygiene
      students.
AB  - PURPOSE: Musculoskeletal disorders (MSDs) are a significant occupational health
      issue for the dental hygiene profession. There is increasing evidence that these
      problems commence during undergraduate training; however, there is a surprising
      lack of studies investigating how MSD develops in student groups over the course
      of their study. The aim of this study was to determine the longitudinal MSD
      trends among a cohort of undergraduate dental hygiene students at an Australian
      university. METHODS: A previously validated self-reporting questionnaire was
      distributed to dental hygiene students in 3 consecutive years from 2008 to 2010.
      RESULTS: MSDs were most commonly reported in the neck (ranging from 66 to 68%)
      and lower back (ranging from 61 to 68%), with a marked increase in reported lower
      back pain by the final year of study. CONCLUSION: This study not only supports
      mounting evidence that MSDs are a common problem for dental hygiene students, but
      further demonstrates the magnitude of this occupational health issue across the
      training program. These findings are concerning for a group yet to embark on
      their professional careers, given that it raises some serious questions about
      career longevity and the efficacy of preventive measures.

PMID- 24563052
TI  - Point-of-care HbA1c screening predicts diabetic status of dental patients.
AB  - PURPOSE: Mutual production of proinflammatory cytokines causes a deleterious
      cyclic relationship between uncontrolled diabetes and periodontal disease. The
      prevalence of diabetes is escalating out of control. Early detection of pre
      diabetes and diabetes may respectively prevent or delay disease onset and
      eliminate or decrease complications. The dental office offers an opportune site
      for diabetes screening. This study investigated the ability to precisely screen
      previously unidentified dental patients for diabetes and pre-diabetes. METHODS:
      In this predictive correlational study, participants were chosen by convenience
      sampling, and were included based on self-proclaimed risk factors. A point-of
      care (POC) fingerstick HbA1c screening identified participants for confirming
      venous HbA1c laboratory screenings. Kendall's tau analyzed the relationship
      between POC HbA1c results and classification as diabetic or pre-diabetic based on
      laboratory HbA1c results. Chi Square, Likelihood Ratio, Cramer's V and Lambda
      compared the expected and observed results. RESULTS: Of the 104 diabetes risk
      questionnaires completed, 75 participants were included in the POC screening. Of
      these, 34 (71% female and 29% male) had HbA1c levels at or above the American
      Diabetes Association's (ADA) recommended 5.7% cut-point for pre-diabetes. Three
      participants were less than age 44, 10 were 44 to 57, and 21 were over 57.
      Laboratory results categorized 6 participants as normoglycemic and 28 with HbA1c
      greater than or equal to 5.7%. Kendall's tau (p=0.004) determined POC results can
      predict diabetic or pre-diabetic laboratory group assignment. Pearson's chi
      square (p=0.004), Likelihood ratio (p=0.004) and Cramer's V (p<0.001) concluded a
      relationship existed between group assignment based on POC HbA1c results and
      those of subsequent laboratory HbA1c results; Lambda (p=0.145) did not.
      CONCLUSION: Within the limits of this study, it was established that a safe and
      minimally invasive dental chair-side POC HbA1c screening unveiled previously
      unidentified diabetic and pre-diabetic patients.

PMID- 24563053
TI  - Iatro-compliance: an unintended consequence of excessive autonomy in long term
      care facilities.
AB  - PURPOSE: Periodontal disease and caries remain the most prevalent preventable
      chronic diseases for seniors. Seniors transitioning into long term care
      facilities (LTCFs) often present with oral health challenges linked to systemic
      diseases, plaque control, psychomotor skills and oral health literacy. Many
      retain a discernible level of physical and cognitive ability, establishing
      considerable autonomy. This study examines the effect of autonomy on residents'
      ability to perform oral hygiene. METHODS: Descriptive data were developed
      utilizing mixed methodology on a convenience sample of 12 residents and 7 care
      staff of a LTCF. One-on-one interviews consisted of questions about demographics,
      and exploration of the influence of ageism, respect and time constraints on
      resident autonomy in oral care practices. RESULTS: Data suggests shortcomings,
      such as failure of the staff to ensure oral hygiene oversight and failure of the
      resident to ask for assistance. Autonomy, while laudable, was used by residents
      to resist staff assistance, partially motivated by residents' lack of confidence
      in care staff oral hygiene literacy and skills. In turn, by honoring resident's
      independence, the staff enabled excessive autonomy to occur creating an
      environment of iatro-compliance. CONCLUSION: While it is beneficial to encourage
      autonomy, oversight and education must remain an integral component of oral
      hygiene care in this population. Improved oral hygiene skills can be fostered in
      LTCFs by utilizing the current oral health care workforce. Registered dental
      hygienists (RDHs), under indirect supervision of a dentist, can fulfill the role
      of an oral health care director (OHCD) in LTCFs. A director's presence in a
      facility can decrease staff caused iatro-compliance and increase oral hygiene
      skills and literacy of the residents, while enhancing their autonomy through
      education and support.

PMID- 24563054
TI  - A single-session testing protocol to determine critical power and W'.
AB  - PURPOSE: Critical power (CP), and the finite capacity to perform work above CP
      (W'), can be determined using a 3-min "all-out" cycling test (3MT). This protocol
      requires two laboratory visits: an incremental exercise test, followed by a 3MT
      on a separate day. The purpose of this study was to establish whether an
      incremental exercise test and a 3MT performed during a single laboratory visit
      can be used to accurately determine CP and W'. METHODS: Twelve participants
      completed two experimental protocols: (1) Combined protocol: an incremental
      exercise test followed by a 3MT, with 20 min of recovery between exercise bouts;
      and (2) Independent protocol: the conventional 3MT protocol, performed on a
      separate day. RESULTS: CP determined from the Combined (254 +/- 117 W) and
      Independent (256 +/- 118 W) protocols were not different (p = 0.40). Similarly,
      W' was not different (p = 0.96) between the Combined (13.7 +/- 3.9 kJ) and
      Independent (13.7 +/- 4.5 kJ) protocols. Linear regression revealed a strong
      level of measurement agreement between the protocols for CP and W', evidenced by
      high R(2) values (>=0.85) and marginal standard errors of the estimates (CP = 5
      W; W' = 1.81 kJ). CONCLUSION: A Combined protocol, consisting of an incremental
      exercise test followed by a 3MT, provides an accurate and valid method to
      determine an individual's CP and, to a lesser extent, W'. Furthermore, this
      protocol permits the measurement of the gas-exchange threshold and peak O2 uptake
      and, consequently, the moderate, heavy, and severe exercise-intensity domains may
      be defined within a single exercise-testing session.

PMID- 24563055
TI  - Atrial functional and geometrical remodeling in highly trained male athletes: for
      better or worse?
AB  - PURPOSE: Highly trained athletes have an increased risk of atrial arrhythmias.
      Atrial geometrical and functional remodeling may be the underlying substrate. We
      analyze and relate atrial size, deformation and performance in professional
      handball players compared with non-sportive subjects. METHODS: 24 Professional
      handball players and 20 non-sportive males were compared. All subjects underwent
      an echocardiographic study with evaluation of left (LA), right atrial (RA)
      dimensions and deformation by strain (Sa) and strain rate (SRa). Atrial
      performance was assessed from the atrial stroke volume (SV). With computational
      geometrical models, we studied the relation between atrial volumes, strains and
      SV and compared atrial working conditions. We estimated the functional reserve
      and a resulting average wall stress. RESULTS: LA and RA volumes were larger in
      athletes than in controls (35.2 +/- 8.8 vs. 24.8 +/- 4.3 ml/m(2), p < 0.01 and
      29.0 +/- 8.4 vs. 19.0 +/- 5.1 ml/m(2), p < 0.01 respectively). LASa and RASa
      during active atrial contraction were decreased in athletes (-12.2 +/- 2.0 vs. 
      14.5 +/- 2.1%, p < 0.01 and -12.1 +/- 1.8 vs. -14.2 +/- 1.5%, p < 0.01
      respectively). LASV was similar between groups (6.6 +/- 1.4 vs. 7.3 +/- 1.1 ml, p
      = 0.19) and RASV was lower in athletes (6.2 +/- 1.3 vs. 7.2 +/- 1.1 ml, p <
      0.01). Computational models showed that this different operational mode
      potentially increases performance reserve, but at the cost of higher atrial wall
      stress. CONCLUSION: A proportion of athletes with enlarged LA and RA showed
      different atrial contractile performance, likely resulting in atria working at
      higher wall stress.

PMID- 24563056
TI  - Effectiveness of electrical noise in reducing postural sway: a comparison between
      imperceptible stimulation applied to the anterior and to the posterior leg
      muscles.
AB  - PURPOSE: The aim of this study was to investigate whether subsensory electrical
      noise stimulation applied over the tibialis anterior (TA) muscles may reduce
      postural oscillations during quiet stance and to compare such reductions with
      those obtained by applying the noise stimulation over the triceps surae (TS)
      muscles. The rationale relies on the use of noise stimulation to enhance the
      sensitivity of sensory receptors, thereby improving the performance of the
      postural control system. As recent evidence suggested that the TA muscle might be
      a better source of proprioceptive information during quiet stance than the TS
      muscles, the main hypothesis of the present study was that subsensory noise
      stimulation applied to the TA muscles should be more efficient for postural
      stabilization than a similar stimulation to the TS. METHODS: Participants had
      their postural steadiness assessed while subsensory electrical noise was applied
      bilaterally to their TA or TS muscles and also while the stimulation was applied
      bilaterally to both TA and TS muscles. No stimulation was delivered in the
      control condition. RESULTS: Time-domain and frequency-domain parameters based on
      center of mass and center of pressure signals were significantly reduced when
      noise stimulation was applied to the anterior and/or to the posterior leg
      muscles. No consistent differences in postural sway parameters were observed
      among the stimulation conditions. CONCLUSIONS: This is the first investigation
      showing that subsensory stimulation applied over the TA muscles alone is
      effective in attenuating postural sway, with TS stimulation being equally
      effective. These findings may have useful applications for the development of
      medical/rehabilitation devices designed to improve postural steadiness in people
      with balance impairments.

PMID- 24563069
TI  - Improving outcome of bariatric surgery: best practices in an accredited surgical
      center.
AB  - The number of laparoscopic bariatric procedures being performed in the USA has
      increased dramatically in the past decade. Because of limited health-care
      resources, hospital administrators and insurance carriers are placing emphasis on
      length of stay and patient outcomes. The goal of this study was to evaluate the
      feasibility and safety of a clinical pathway in managing patients undergoing
      bariatric surgery in a Metabolic and Bariatric Surgery Accreditation and Quality
      Improvement Program (MBSAQIP) accredited center. The setting was a university
      hospital in USA. A retrospective analysis of data collected prospectively on
      patients undergoing bariatric surgery at St Luke's University was performed.
      Patients included underwent either a laparoscopic Roux-en-Y gastric Bypass
      (LRYGB) or laparoscopic sleeve gastrectomy (LSG). Patients were subjected to a
      clinical protocol and discharged when discharge criteria were met. The primary
      outcomes were length of stay, 30 day readmission, complication, and reoperation
      rates. A cost analysis of the savings accrued was also performed. Two hundred
      twenty-nine patients were included in our analysis (80.4% females and 19.6%
      males). Seventy-one patients (31%) underwent LSG, and 158 patients (69%)
      underwent LRYGB. The average length of stay was 32.45 h (range 24-72 h). The 30
      day readmission rate was 3.0% (7/229 patients). The 30 day complication rate
      (including intervention, reintubation, and reoperation) was 2.6% (6/229). The 30
      day mortality rate was 0. The average prospective cost savings were $2,016 and
      $1,209 per LRYGB and LSG patient, respectively. Our bariatric surgery clinical
      protocol is feasible and safe with substantial prospective cost savings at St
      Luke's University and Health Network. Patients subjected to our protocol have low
      readmission and complication rates. Further studies are needed to fully elucidate
      the benefit of this innovative new protocol in bariatric surgery.

PMID- 24563068
TI  - Effect of chemotherapy on quality of life in patients with non-small cell lung
      cancer.
AB  - PURPOSE: This study was conducted to evaluate the extent to which quality of life
      (QoL) assessment has been incorporated into clinical trials of patients with
      advanced non-small cell lung cancer (NSCLC) receiving palliative chemotherapy.
      PATIENTS AND METHODS: Phase III trials for patients with NSCLC treated with
      palliative chemotherapy were identified by a literature search of PubMed. All
      abstracts and relevant articles from August 1986 to October 2011 were reviewed.
      The primary focus was on (a) whether these articles had incorporated QoL as an
      endpoint, (c) what instruments were used to measure QoL and (c) impact of
      chemotherapy on QoL. RESULTS: There were 3,780 items indexed under 'quality of
      life and lung cancer'. One hundred three studies were identified which measured
      QoL using validated QoL instruments. Fifty-five of these trials assessed the
      effects of palliative chemotherapy on QoL in patients with advanced NSCLC. The
      European Organisation for Research and Treatment of Cancer-Quality of Life
      Questionnaire was the most widely used questionnaire; other commonly used
      measurement scales used were the Functional Assessment of Cancer Therapy-Lung and
      the Lung Cancer Symptom Scale. The majority of studies showed that chemotherapy
      had a positive impact on QoL and disease-specific symptoms. CONCLUSION: It is now
      widely accepted that QoL should be considered as a primary endpoint of treatment
      in patients with advanced lung cancer both in clinical practice and clinical
      trials to further define meaningful response. As the traditional outcome measures
      of survival and tumour response are poor in this population, QoL assessment may
      offer a more comprehensive approach to evaluating the relative risks and benefits
      associated with treatments.

PMID- 24563070
TI  - Relative contribution of modifiable versus non-modifiable factors as predictors
      of racial variance in roux-en-Y gastric bypass weight loss outcomes.
AB  - African-Americans have been shown to have poorer weight loss outcomes after
      bariatric surgery, and many reasons for such outcomes have been postulated,
      including metabolic and genetic differences, socioeconomic factors, and
      differences in culture. African-Americans have also been noted to have
      differences from the majority population in other psychosocial correlates to
      weight loss outcomes. However, the relative contribution of targetable factors in
      relation to non-modifiable factors to such outcomes remains unclear. African
      American and Caucasian patients who had received a Roux-en-Y gastric bypass and
      returned for a 12-month follow up appointment (n = 415) were selected for
      retrospective analysis. A stepwise hierarchical regression of 12 month percent
      excess weight loss (% EWL) was conducted that included race after controlling for
      psychosocial and demographic factors previously linked to postsurgical outcomes.
      These variables were then compared between racial groups using independent t
      tests and chi-square analyses. Race remained a significant predictor of % EWL
      after controlling for pertinent psychosocial and demographic variables. Age and
      preoperative BMI were significant negative predictors, whereas presurgical BMI
      loss and Caucasian race were positive (p < 0.05). Percentage of follow-up
      appointment attendance was borderline significant. No significant racial
      differences were noted in these variables. Non-modifiable factors inherent to
      race such as metabolism play small but significant roles in the postoperative
      weight loss in African-American patients. Further research is needed to better
      elucidate the roles of targetable factors in outcomes, particularly adherence and
      pay status as their evaluation in this study was limited. 

PMID- 24563071
TI  - Angiopoietin-like protein 2 regulates endothelial colony forming cell
      vasculogenesis.
AB  - Angiopoietin-like 2 (ANGPTL2) has been reported to induce sprouting angiogenesis;
      however, its role in vasculogenesis, the de novo lumenization of endothelial
      cells (EC), remains unexplored. We sought to investigate the potential role of
      ANGPTL2 in regulating human cord blood derived endothelial colony forming cell
      (ECFC) vasculogenesis through siRNA mediated inhibition of ANGPTL2 gene
      expression. We found that ECFCs in which ANGPTL2 was diminished displayed a
      threefold decrease in in vitro lumenal area whereas addition of exogenous ANGPTL2
      protein domains to ECFCs lead to increased lumen formation within a 3 dimensional
      (3D) collagen assay of vasculogenesis. ECFC migration was attenuated by 36 % via
      ANGPTL2 knockdown (KD) although proliferation and apoptosis were not affected. We
      subsequently found that c-Jun NH2-terminal kinase (JNK), but not ERK1/2,
      phosphorylation was decreased upon ANGPTL2 KD, and expression of membrane type 1
      matrix metalloproteinase (MT1-MMP), known to be regulated by JNK and a critical
      regulator of EC migration and 3D lumen formation, was decreased in lumenized
      structures in vitro derived from ANGPTL2 silenced ECFCs. Treatment of ECFCs in 3D
      collagen matrices with either a JNK inhibitor or exogenous rhTIMP-3 (an inhibitor
      of MT1-MMP activity) resulted in a similar phenotype of decreased vascular lumen
      formation as observed with ANGPTL2 KD, whereas stimulation of JNK activity
      increased vasculogenesis. Based on gene silencing, pharmacologic, cellular, and
      biochemical approaches, we conclude that ANGPTL2 positively regulates ECFC
      vascular lumen formation likely through its effects on migration and in part by
      activating JNK and increasing MT1-MMP expression.

PMID- 24563072
TI  - Mixed aortic valve disease in the young: initial observations.
AB  - The short-term surgical results for mixed aortic valve disease (MAVD) and the
      long-term effects on the left ventricle (LV) are unknown. Retrospective review
      identified patients with at least both moderate aortic stenosis (AS) and aortic
      regurgitation (AR) before surgical intervention. A one-to-one comparison cohort
      of patients with MAVD not referred for surgical intervention was identified. The
      45 patients in this study underwent surgical management for MAVD. A control group
      of 45 medically managed patients with MAVD also was identified. Both groups had
      elevated LV end-diastolic volume (EDV), elevated LV mass, a normal LV mass:volume
      ratio (MVR), and a normal ejection fraction. Both groups had diastolic
      dysfunction shown by early diastolic pulsed-Doppler mitral inflow/early diastolic
      tissue Doppler velocity z-score. The LV end-diastolic pressure (EDP) was
      correlated with age (R = 0.4; p = 0.03) and LV MVR (R = 0.4; p = 0.03) but not
      with AS, AR, or the score combining gradient and LV size. As shown by 6- to 12
      month postoperative echocardiograms, aortic valve gradients and AR significantly
      improved (gradient 65 +/- 17 to 28 +/- 18 mmHg, p = 0.01; median regurgitation
      grade moderate to mild; p < 0.01), LV EDV normalized, and LV mass significantly
      improved (p < 0.01). Diastolic dysfunction was unchanged. Symptoms did not
      correlate with any measured parameter, but the preoperative symptoms resolved. In
      conclusion, despite diastolic dysfunction, systolic function is invariably
      preserved, and symptoms are not correlated with aortic valve function or LV EDP.
      Current surgical practice preserves LV mechanics and results in short-term
      improvement in valve function and symptoms.

PMID- 24563073
TI  - Parental education level is associated with clustering of metabolic risk factors
      in adolescents independently of cardiorespiratory fitness, adherence to the
      Mediterranean diet, or pubertal stage.
AB  - Few studies have reported associations between clustering metabolic risk factors
      and socioeconomic status (SES) in youth. This study aimed to analyze the
      association between clustering metabolic risk factors and SES in adolescents. It
      was hypothesized that SES is inversely related to clustering metabolic risk
      factors. This 2009 cross-sectional school-based study investigated 517 Portuguese
      adolescents ages 15-18 years. The study considered the age- and sex-adjusted z
      scores for the ratio of total cholesterol/high-density lipoprotein, homeostasis
      model, triglycerides, and systolic blood pressure, and a metabolic risk score was
      constructed by summing all the z-scores (>=1 standard deviation was considered
      high risk). Cardiorespiratory fitness was estimated by the 20 m shuttle-run test
      and dietary intake by a food frequency questionnaire. The best of parental
      education was used as a proxy measure of SES. The results showed that adolescents
      with low SES were more likely to have a high metabolic risk score (odds ratio
      [OR], 1.96; p < 0.020) regardless of cardiorespiratory fitness, adherence to the
      Mediterranean diet, or pubertal stage. In conclusion, a lower SES was associated
      with increased risk for a high metabolic risk score among Azorean adolescents
      after adjustment for pubertal stage, adherence to the Mediterranean diet, and
      cardiorespiratory fitness. Future health-promotion strategies among Azorean
      adolescents should consider the impact of SES on their health.

PMID- 24563074
TI  - Incidences and sociodemographics of specific congenital heart diseases in the
      United States of America: an evaluation of hospital discharge diagnoses.
AB  - Current estimates of the incidence of congenital heart disease (CHD) are derived
      from small clinical studies and metaanalyses. For the true incidence of CHD in
      the United States of America to be estimated, a single large representative
      population must be analyzed. All the data in this study were derived from the
      Nationwide Inpatient Sample database. The study determined the overall and lesion
      specific incidences of CHD diagnoses among all birth hospitalizations in 2008,
      stratified by race, gender, socioeconomic status, and hospital geographic
      location. The study identified 13,093 CHD diagnoses among 1,204,887 birth
      hospitalizations, yielding an incidence of 10.8 per 1,000, with a predominance of
      mild lesions and septal defects. Atrial septal defect (ASD) and pulmonic stenosis
      were more common among females, whereas aortic stenosis, coarctation of the
      aorta, hypoplastic left heart syndrome, and d-transposition of great arteries
      were more common among males. No racial difference was observed in the overall
      CHD incidence. However, isolated patent ductus arteriosus (PDA) and ventricular
      septal defects (VSDs) were more common among Caucasians, whereas ASDs were more
      common among Hispanics. The incidences of CHD diagnoses were similar for all
      socioeconomic classes except the lowest socioeconomic class, which had a
      significantly lower CHD incidence. There was no geographic or seasonal variation
      in CHD incidence. This study demonstrated the incidence of echocardiographically
      confirmed CHD diagnosis to be 10.8 per 1,000 live births, marked by a high
      proportion of mild cardiac lesions and isolated PDAs. The high incidence of
      isolated PDAs in this study may be explained by the inclusion of only CHD
      diagnoses during birth hospitalization. 

PMID- 24563075
TI  - Sorafenib in metastatic thyroid cancer: a systematic review.
AB  - BACKGROUND: Sorafenib was recently approved by the U.S. Food and Drug
      Administration for radioiodine-resistant metastatic differentiated thyroid cancer
      (DTC). In addition, two drugs (vandetanib and cabozantinib) have received U.S.
      Food and Drug Administration approval for use in medullary thyroid cancer (MTC).
      Several published phase II trials have investigated the efficacy of sorafenib in
      thyroid cancers, but to date, results from those studies have not been compared.
      METHODS: A systematic review of the literature was performed to assess response
      rate, median progression-free survival, and adverse events associated with
      sorafenib therapy for metastatic thyroid cancers. RESULTS: This review included
      seven trials involving 219 patients: 159 with DTC (papillary, follicular, and
      poorly differentiated), 52 with MTC, and 8 with anaplastic thyroid cancer. No
      study reported complete responses to treatment. Overall partial response, stable
      disease, and progressive disease rates were 21%, 60%, and 20%, respectively. The
      median progression-free survival was 18 months for patients with all subtypes of
      thyroid cancer. Drug was discontinued in 16% of patients because of toxicities or
      intolerance, and the dose was reduced in a further 56%. Side effects with an
      incidence >= 50% were hand-foot syndrome (74%), diarrhea (70%), skin rash (67%),
      fatigue (61%), and weight loss (57%). Deaths not related to progressive disease
      occurred in nearly 4% of patients. CONCLUSION: Treatment with sorafenib in
      patients with progressive DTC and MTC is a promising strategy, but the adverse
      event rate is high, leading to a high rate of dose reduction or discontinuation.
      Consequently, sorafenib use in patients with metastatic thyroid cancer requires
      careful selection of patients and careful management of side effects.

PMID- 24563077
TI  - Polymorphisms in microRNA-related genes are associated with survival of patients
      with T-cell lymphoma.
AB  - OBJECTIVE: Elaborate evaluation of prognosis of T-cell lymphoma (TCL) is vital
      for current therapy and future stratified and individualized therapy. MicroRNAs
      (miRNAs) play important roles in cancer development and prognosis. We aimed to
      assess the effects of single nucleotide polymorphisms (SNPs) in miRNA-related
      genes on the survival of patients with TCL. PATIENTS AND METHODS: We genotyped 13
      SNPs selected from 12 miRNA-related genes in 220 TCL patients and explored the
      association of SNPs with survival. RESULTS: Among the 13 SNPs, four (DROSHA
      rs6877842, DICER rs3742330, mir149 rs2292832, and mir499 rs3746444) were
      significantly associated with TCL survival after adjusting for subtype and
      International Prognostic Index score. In stratified analyses, all four SNPs
      remained significantly associated with survival in patients with mature T type.
      Of the four SNPs, only mir149 rs2292832 was not significantly associated with
      survival in patients with an International Prognostic Index score of 0-1.
      Furthermore, a dose-dependent cumulative effect of the four SNPs on TCL survival
      was observed by counting the number of unfavorable genotypes. Survival tree
      analysis also showed higher order interactions between these SNPs. CONCLUSION:
      The results suggested that miRNA-related polymorphisms are associated with
      survival of TCL patients; thus, they may be used individually and jointly to
      predict survival of patients with TCL.

PMID- 24563076
TI  - New routes to targeted therapy of intrahepatic cholangiocarcinomas revealed by
      next-generation sequencing.
AB  - BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is a subtype of primary liver
      cancer that is rarely curable by surgery and is rapidly increasing in incidence.
      Relapsed ICC has a poor prognosis, and current systemic nontargeted therapies are
      commonly extrapolated from those used in other gastrointestinal malignancies. We
      hypothesized that genomic profiling of clinical ICC samples would identify
      genomic alterations that are linked to targeted therapies and that could
      facilitate a personalized approach to therapy. METHODS: DNA sequencing of
      hybridization-captured libraries was performed for 3,320 exons of 182 cancer
      related genes and 36 introns of 14 genes frequently rearranged in cancer. Sample
      DNA was isolated from 40 MUm of 28 formalin-fixed paraffin-embedded ICC specimens
      and sequenced to high coverage. RESULTS: The most commonly observed alterations
      were within ARID1A (36%), IDH1/2 (36%), and TP53 (36%) as well as amplification
      of MCL1 (21%). Twenty cases (71%) harbored at least one potentially actionable
      alteration, including FGFR2 (14%), KRAS (11%), PTEN (11%), CDKN2A (7%), CDK6
      (7%), ERBB3 (7%), MET (7%), NRAS (7%), BRCA1 (4%), BRCA2 (4%), NF1 (4%), PIK3CA
      (4%), PTCH1 (4%), and TSC1 (4%). Four (14%) of the ICC cases featured novel gene
      fusions involving the tyrosine kinases FGFR2 and NTRK1 (FGFR2-KIAA1598, FGFR2
      BICC1, FGFR2-TACC3, and RABGAP1L-NTRK1). CONCLUSION: Two thirds of patients in
      this study harbored genomic alterations that are associated with targeted
      therapies and that have the potential to personalize therapy selection for to
      individual patients.

PMID- 24563078
TI  - Continuous-infusion topotecan and erlotinib: a study in topotecan-pretreated
      ovarian cancer assessing shed collagen epitopes as a marker of invasiveness.
AB  - BACKGROUND: Continuous-infusion topotecan with erlotinib has the potential to
      reverse topotecan resistance due to drug efflux mechanisms. We assessed the
      activity of such a regimen in ovarian cancer patients previously failing bolus
      topotecan. Assay for shed collagen epitopes recognized by antibody HU177 during
      treatment explored its ability to reflect tumor invasion. METHODS: Topotecan 0.4
      mg/m(2) per day was administered by continuous infusion for 9-10 days every 3
      weeks. Erlotinib, 150 mg orally, was administered on days 1-10 of each cycle.
      Cycles were repeated until progression or toxicity. Serum for shed HU177 collagen
      epitopes was collected weekly. This was a two-stage design to detect a CA-125
      response rate of at least 20% in 30 patients after completing two treatment
      cycles. The trial would be terminated early if there were less than two CA-125
      responses in 16 patients. Four or more CA-125 responses in 30 patients would
      justify further study of this regimen in prior topotecan treatment failures.
      RESULTS: Six patients were enrolled, with four receiving three or more cycles and
      one achieving a partial response by cancer antigen 125 (CA-125) criteria. Shed
      epitope levels became undetectable on at least one measurement in all patients
      who received three or more cycles (Fig. 1A) and reappeared concomitantly with
      rises in CA-125 and clinical progression (Fig. 1B). After logistical delays, the
      trial was closed by the sponsor's decision to stop developing erlotinib in
      ovarian cancer. FIGURE 1: Monitoring of combination treatment. A, B, C, D, and F
      refer to patients. (A):: Topotecan and erlotinib. (B):: CA-125 in units/mL.
      CONCLUSION: Continuous-infusion topotecan with erlotinib was found safe in six
      pretreated ovarian cancer patients; one met CA-125 criteria for partial response.
      Serial shed epitope levels to reflect invasiveness deserve further study.

PMID- 24563080
TI  - Intracellular Ca(2+) overload induced by extracellular Ca(2+) entry plays an
      important role in acute heart dysfunction by tentacle extract from the jellyfish
      Cyanea capillata.
AB  - The exact mechanism of acute heart dysfunction caused by jellyfish venom remains
      unclear for the moment. In the present study, we examined the problem caused by
      the tentacle extract (TE) from the jellyfish Cyanea capillata at the levels of
      whole animal, isolated heart, primarily cultured cardiomyocytes, and
      intracellular Ca(2+). The heart indexes, including HR, APs, LVPs, and MMLs, were
      all decreased significantly by TE in both whole animal and Langendorff-perfused
      isolated heart model. Imbalance of cardiac oxygen supply and demand also took
      place. In both Ca(2+)-containing and Ca(2+)-free bathing solutions, TE could
      cause obvious cytoplasmic Ca(2+) overload in NRVMs, but the cytoplasmic Ca(2+)
      increased faster, Ca(2+) overload peaks arrived earlier, and the morphological
      changes were more severe under the extracellular Ca(2+)-containing condition. L
      type Ca(2+) channel blockers, as well as the inhibitor of ryanodine receptor
      (ryanodine), could improve the viability of NRVMs. Moreover, diltiazem
      significantly inhibited the acute heart dysfunction caused by TE in both
      Langendorff isolated heart model and whole animal. These results suggested that
      intracellular Ca(2+) overload induced by extracellular Ca(2+) entry plays an
      important role in acute heart failure by TE from the jellyfish C. capillata.
      Inhibition of extracellular Ca(2+) influx is a promising antagonistic alternative
      for heart damage by jellyfish venom. 

PMID- 24563081
TI  - Nov/CCN3 regulates long-term repopulating activity of murine hematopoietic stem
      cells via integrin alphavbeta3.
AB  - Throughout life, hematopoietic stem cells (HSCs) sustain the blood cell supply
      through their capacities for self-renewal and multilineage differentiation. These
      processes are regulated within a specialized microenvironment termed the 'niche'.
      Here, we show a novel mechanism for regulating HSC function that is mediated by
      nephroblastoma overexpressed (Nov/CCN3), a matricellular protein member of the
      CCN family. We found that Nov contributes to the maintenance of long-term
      repopulating (LTR) activity through association with integrin alphavbeta3 on
      HSCs. The resultant beta3 integrin outside-in signaling is dependent on
      thrombopoietin (TPO), a crucial cytokine involved in HSC maintenance. TPO was
      required for Nov binding to integrin alphavbeta3, and stimulated Nov expression
      in HSCs. However, in the presence of IFNgamma, a cytokine known to impair HSC
      function, not only was TPO-induced expression of Nov suppressed, but the LTR
      activity was conversely impaired by TPO-mediated ligation of integrin alphavbeta3
      with exogenous ligands, including Nov, as well. Thus, Nov/integrin alphavbeta3
      mediated maintenance of HSCs appears to be modulated by simultaneous stimulation
      by other cytokines. Our finding suggests that this system contributes to the
      regulation of HSCs within the bone marrow niche. 

PMID- 24563082
TI  - A novel mutation of the transcobalamin II gene in an infant presenting with
      hemophagocytic lymphohistiocytosis.
AB  - Transcobalamin II (TC II) deficiency is a rare disorder of cobalamin (CBL,
      vitamin B12) metabolism that occurs due to mutations in transcobalamin gene
      (TCN2). Hemophagocytic lymphohistiocytosis (HLH) in contrast is a syndrome
      characterized by uncontrolled immune response with hyperinflammation. A 2-month
      old male baby was admitted with complaints of fever, cough, diarrhea, and
      respiratory distress. The parents were first cousins. The baby exhibited five of
      the eight diagnostic criteria for HLH-2004 and was diagnosed as HLH. A second
      bone marrow aspiration demonstrated megaloblastic changes in the erythroid
      series. The patient's vitamin B12 level was normal; however, hyperhomocysteinemia
      was present. A genetic deficiency of TC II was suspected. The patient and his
      parents were tested for TCN2 mutation. He had a homozygote mutation that was not
      included in Human 'Gene Mutation Database Cardiff'. The patient was treated with
      intramuscular vitamin B12, which was followed by improvement in both clinical and
      laboratory findings. He was 12 months old at the time of this report, with normal
      physical and neuromotor development. In this case presenting with the clinical
      and laboratory findings of HLH, TC II deficiency was diagnosed. A new mutation
      was found that was not reported before. Potential causative mechanisms of HLH
      induced by defects of cobalamin synthesis merit further investigation.

PMID- 24563083
TI  - Testing the Acquired Preparedness Model: Predicting College Student Gambling
      Frequency and Symptomatology.
AB  - The acquired preparedness model posits that impulsivity influences the
      development of outcome expectancies that then influence the engagement in a
      specific risk taking behavior. The purpose of this study was to test the acquired
      preparedness model for gambling behavior of college students using a
      multidimensional approach to impulsivity. Employing a structural equation
      approach, it was predicted that a full mediational model that includes multiple
      dimensions of impulsivity and multiple outcome expectancies would predict
      gambling frequency and gambling symptomatology. Support was found for the
      acquired preparedness model in understanding why some college students gamble
      more frequently or problematically. Specifically, better model fit was found for
      the full mediational model that included outcome expectancies to predict both
      frequency and gambling symptomatology than the model that included the direct
      relation between impulsivity and gambling. 

PMID- 24563084
TI  - Evaluation of the satiating properties of a nutraceutical product containing
      Garcinia cambogia and Ascophyllum nodosum extracts in healthy volunteers.
AB  - A nutraceutical product composed of a combination of Garcinia cambogia, l
      carnitine and a seaweed extract of Ascophyllum nodosum has been recently
      developed. The aim of the present study was to characterize its effects on
      subjective satiety sensations and food preferences in healthy volunteers. In a
      crossover design, 28 subjects (21 females and 7 males, aged 31 +/- 5, BMI 22.6 +/
      1.7) were randomly assigned to receive the active treatment (LIS) or placebo
      (PL) over one week. At the end of each treatment period, subjects were instructed
      to consume ad libitum a test meal. Food preferences and appetite sensations were
      evaluated by means of the Leeds Food Preferences Questionnaire and visual analog
      scales, before and after meal, over three hours. There were no differences in
      energy intake between study groups. LIS was associated with a reduction in
      subjective hunger sensations (p = 0.018) and to an increase in satiety (p = 0.02)
      and fullness (p = 0.01) ratings. The preference for high fat foods was reduced
      after consuming the test meal in both study groups. There was a significant
      effect of LIS treatment on food explicit liking and implicit wanting, as
      evidenced by an increase in preference for sweet foods (relative to savory foods;
      p = 0.03 and p = 0.004, respectively), but no differences were observed regarding
      the preference for low or high fat foods (NS). These results provide proof of
      principle for the satiating properties of a nutraceutical containing Garcinia
      cambogia, Ascophyllum nodosum extract and l-carnitine and suggest that it might
      be useful as an appetite modulator.

PMID- 24563085
TI  - Meaningful use and the patient portal: patient enrollment, use, and satisfaction
      with patient portals at a later-adopting center.
AB  - Many physicians are adopting patient portals in response to governmental
      incentives for meaningful use (MU), but the stage 2 requirements for portal use
      may be particularly challenging for newer electronic health record (EHR) users.
      This study examined enrollment, use based on MU requirements, and satisfaction in
      a recently adopting fee-for-service multispecialty system. Between 2010 and 2012,
      overall portal enrollment increased from 13.2% to 23.1% but varied substantially
      by physician specialty. In 2013, more than 97% of physicians would have met
      requirements for a stage 2 MU utilization measure requiring that patients
      download personal health information, but only 38% of all physicians (87% of
      primary care physicians [PCPs] and 37% of other specialists) would have met e
      mail requirements. Satisfaction with the portal overall and with portal-based e
      mails was high. These results suggest that later-adopting PCPs can succeed in
      providing satisfactory record and e-mail access but specialists may find reaching
      e-mail thresholds more difficult. 

PMID- 24563091
TI  - Effect of oxygen-breathing during a decompression-stop on bubble-induced platelet
      activation after an open-sea air dive: oxygen-stop decompression.
AB  - PURPOSE: We highlighted a relationship between decompression-induced bubble
      formation and platelet micro-particle (PMP) release after a scuba air-dive. It is
      known that decompression protocol using oxygen-stop accelerates the washout of
      nitrogen loaded in tissues. The aim was to study the effect of oxygen deco-stop
      on bubble formation and cell-derived MP release. METHODS: Healthy experienced
      divers performed two scuba-air dives to 30 msw for 30 min, one with an air deco
      stop and a second with 100% oxygen deco-stop at 3 msw for 9 min. Bubble grades
      were monitored with ultrasound and converted to the Kisman integrated severity
      score (KISS). Blood samples for cell-derived micro-particle analysis (AnnexinV
      for PMP and CD31 for endothelial MP) were taken 1 h before and after each dive.
      RESULTS: Mean KISS bubble score was significantly lower after the dive with
      oxygen-decompression stop, compared to the dive with air-decompression stop (4.3
      +/- 7.3 vs. 32.7 +/- 19.9, p < 0.001). After the dive with an air-breathing
      decompression stop, we observed an increase of the post-dive mean values of PMP
      (753 +/- 245 vs. 381 +/- 191 ng/MUl, p = 0.003) but no significant change in the
      oxygen-stop decompression dive (329 +/- 215 vs. 381 +/191 ng/MUl, p = 0.2). For
      the post-dive mean values of endothelial MP, there was no significant difference
      between both the dives. CONCLUSIONS: The Oxygen breathing during decompression
      has a beneficial effect on bubble formation accelerating the washout of nitrogen
      loaded in tissues. Secondary oxygen-decompression stop could reduce bubble
      induced platelet activation and the pro-coagulant activity of PMP release
      preventing the thrombotic event in the pathogenesis of decompression sickness.

PMID- 24563092
TI  - Inflammatory responses of older firefighters to intermittent exercise in the
      heat.
AB  - PURPOSE: Repeated strenuous work in the heat may predispose firefighters to
      augmented immune responses and inflammation. This study examined the immune
      responses in 12 older Firefighters (FF) and 12 older Non-Firefighters (Non-FF),
      and a group of 6 young FF and 6 young Non-FF, following intermittent exercise in
      the heat. METHODS: The participants, matched for age, body surface area, body
      composition, and VO(2peak), cycled 4 * 15 min at moderate-to-high heat production
      (400 W), each followed by 15-min rest, in dry [10-20% relative humidity (RH)] and
      humid (60% RH) heat (35  degrees C). Rectal temperature (T(re)) and heart rate
      (HR) were measured continuously, and blood samples at baseline (PRE) and
      following 60-min recovery (POST) were analyzed for Interleukin (IL)-6, Tumor
      Necrosis Factor (TNF-alpha), C-reactive protein (CRP), platelet count (PLT), and
      mean platelet volume (MPV). RESULTS: No differences were observed for T(re), HR,
      TNF-alpha, CRP, or PLT between the FF and Non-FF in either condition. The Non-FF
      had greater changes in IL-6 (Warm/Dry = +1.10 +/- 0.18, Warm/Humid = +2.94 +/-
      0.74 pg mL(-1)), compared to the FF (Warm/Dry = +0.67 +/- 0.17, Warm/Humid =
      +0.70 +/- 0.33 pg mL(-1)), and MPV at PRE/POST compared to the FF. Between the
      young and older FF and Non-FF, no differences in T(re), HR, PLT, or MPV were
      observed, however, elevated CRP (Warm/Dry) in the older FF, and IL-6 (Warm/Dry)
      and TNF-alpha (both conditions) in the older Non-FF, were observed. CONCLUSIONS:
      The elevated IL-6 in the Non-FF is potentially indicative of increased strain in
      the Non-FF and/or adaptive changes in the FF due to the occupational demands.

PMID- 24563093
TI  - Eccentric exercise-induced muscle damage of pre-adolescent and adolescent boys in
      comparison to young men.
AB  - PURPOSE: This study compared changes in indirect muscle damage markers after
      maximal eccentric exercise of the elbow flexors (EF) among pre-adolescent (9-10
      years), adolescent (14-15 years) and post-adolescent (20-25 years) men to test
      the hypothesis that the magnitude of muscle damage would increase with increase
      in age. METHODS: Thirteen untrained men of each age group performed two bouts
      (ECC1, ECC2) of 30 maximal EF eccentric contractions. Several indirect muscle
      damage markers were measured from the exercised arm before, immediately after,
      and 1-5 days post-exercise. Changes in maximal voluntary concentric contraction
      torque of the EF (MVC), range of motion of the elbow joint, upper arm
      circumference (CIR), muscle passive stiffness, muscle soreness, plasma creatine
      kinase activity and myoglobin concentration after ECC1 and ECC2 were compared
      amongst groups by a mixed-design two-way ANOVA. RESULTS: MVC before exercise was
      smaller (P < 0.05) for pre-adolescent (8.9 +/- 1.9 Nm) than adolescent (25.1 +/-
      3.9 Nm) and adult (35.3 +/- 4.6 Nm), and for adolescent than adult. Changes in
      all variables after ECC1 were smaller (P < 0.05) for pre-adolescent and
      adolescent when compared with adult, and all except CIR changes were smaller (P <
      0.05) for pre-adolescent than adolescent. After ECC2, changes in all variables
      were smaller (P < 0.05) than those after ECC1 for all groups, but the magnitude
      of the changes was different among groups (P < 0.05) in the same way as that
      after ECC1. CONCLUSION: These results indicate that the magnitude of muscle
      damage is increased from pre-adolescent, adolescent to post-adolescent men.

PMID- 24563094
TI  - Acetaminophen and sport performance: doping or what?

PMID- 24563095
TI  - Reply to letter: Acetaminophen and sport performance: doping or what?

PMID- 24563097
TI  - Strong shift from HCO3 (-) to CO 2 uptake in Emiliania huxleyi with
      acidification: new approach unravels acclimation versus short-term pH effects.
AB  - Effects of ocean acidification on Emiliania huxleyi strain RCC 1216 (calcifying,
      diploid life-cycle stage) and RCC 1217 (non-calcifying, haploid life-cycle stage)
      were investigated by measuring growth, elemental composition, and production
      rates under different pCO2 levels (380 and 950 MUatm). In these differently
      acclimated cells, the photosynthetic carbon source was assessed by a (14)C
      disequilibrium assay, conducted over a range of ecologically relevant pH values
      (7.9-8.7). In agreement with previous studies, we observed decreased
      calcification and stimulated biomass production in diploid cells under high pCO2,
      but no CO2-dependent changes in biomass production for haploid cells. In both
      life-cycle stages, the relative contributions of CO2 and HCO3 (-) uptake depended
      strongly on the assay pH. At pH values <= 8.1, cells preferentially used CO2 (>=
      90 % CO2), whereas at pH values >= 8.3, cells progressively increased the
      fraction of HCO3 (-) uptake (~45 % CO2 at pH 8.7 in diploid cells; ~55 % CO2 at
      pH 8.5 in haploid cells). In contrast to the short-term effect of the assay pH,
      the pCO2 acclimation history had no significant effect on the carbon uptake
      behavior. A numerical sensitivity study confirmed that the pH-modification in the
      (14)C disequilibrium method yields reliable results, provided that model
      parameters (e.g., pH, temperature) are kept within typical measurement
      uncertainties. Our results demonstrate a high plasticity of E. huxleyi to rapidly
      adjust carbon acquisition to the external carbon supply and/or pH, and provide an
      explanation for the paradoxical observation of high CO2 sensitivity despite the
      apparently high HCO3 (-) usage seen in previous studies. 

PMID- 24563098
TI  - Isotopic and anatomical evidence of an herbivorous diet in the Early Tertiary
      giant bird Gastornis. implications for the structure of Paleocene terrestrial
      ecosystems.
AB  - The mode of life of the early Tertiary giant bird Gastornis has long been a
      matter of controversy. Although it has often been reconstructed as an apex
      predator feeding on small mammals, according to other interpretations, it was in
      fact a large herbivore. To determine the diet of this bird, we analyze here the
      carbon isotope composition of the bone apatite from Gastornis and contemporaneous
      herbivorous mammals. Based on (13)C-enrichment measured between carbonate and
      diet of carnivorous and herbivorous modern birds, the carbonate delta(13)C values
      of Gastornis bone remains, recovered from four Paleocene and Eocene French
      localities, indicate that this bird fed on plants. This is confirmed by a
      morphofunctional study showing that the reconstructed jaw musculature of
      Gastornis was similar to that of living herbivorous birds and unlike that of
      carnivorous forms. The herbivorous Gastornis was the largest terrestrial tetrapod
      in the Paleocene biota of Europe, unlike the situation in North America and Asia,
      where Gastornis is first recorded in the early Eocene, and the largest Paleocene
      animals were herbivorous mammals. The structure of the Paleocene terrestrial
      ecosystems of Europe may have been similar to that of some large islands, notably
      Madagascar, prior to the arrival of humans. 

PMID- 24563099
TI  - Hyperactivity and tree-top disease induced by the baculovirus AcMNPV in
      Spodoptera exigua larvae are governed by independent mechanisms.
AB  - Although many parasites are known to manipulate the behavior of their hosts, the
      mechanisms underlying such manipulations are largely unknown. Baculoviruses
      manipulate the behavior of caterpillar hosts by inducing hyperactivity and by
      inducing climbing behavior leading to death at elevated positions (tree-top
      disease or Wipfelkrankheit). Whether hyperactivity and tree-top disease are
      independent manipulative strategies of the virus is unclear. Recently, we
      demonstrated the involvement of the protein tyrosine phosphatase (ptp) gene of
      the baculovirus Autographa californica multiple nucleopolyhedrovirus (AcMNPV) in
      the induction of hyperactivity in Spodoptera exigua larvae. Here we show that
      AcMNPV ptp is not required for tree-top disease, indicating that in S. exigua
      baculovirus-induced hyperactivity and tree-top disease are independently induced
      behaviors that are governed by distinct mechanisms. 

PMID- 24563096
TI  - Saponin as regulator of biofuel: implication for ethnobotanical management of
      diabetes.
AB  - There has been a sharp rise in the global prevalence of diabetes, obesity, and
      their comorbid conditions within the last decade prompting significant research
      into possible causes and cure via therapeutic intervention and lifestyle
      adjustments. Here, the molecular bases of antidiabetic plants used in the
      prehistorical treatment of diabetes and obesity are reviewed with particular
      focus on saponin as the phytotherapeutic principle. Until recently, the
      phytotherapeutic potentials of saponins have been masked in the heterogeneity of
      phytochemicals co-extractable during traditional preparations. With improved
      technique of purification and cutting edge biological assay methods, saponins
      have emerged as a regulator of primary biofuel availability through direct
      interaction with energy metabolism, cell signaling, and gene expression. Specific
      cases of lipoprotein lipase/peroxisome proliferator-activated receptor (PPAR)
      gamma/phosphatidylinositide 3-kinase (PI-3-K)/protein kinase B (Akt) activation,
      adiponectin gene upregulation, fatty acid binding protein 4 repression (FABP4),
      and glucose transporter type 4 (Glut4) membrane exocytosis have been documented
      which provide molecular basis for hypocholesterolemic, hypoglycemic, and anti
      obesity manifestations observed in experimental animals following saponin
      treatment. Although intensified research is required to characterize the
      pharmacophoric features in saponins exhibiting these interactions, however, this
      preliminary lead is valuable if the world will be free of diabetes, obesity,
      hypertension, hyperlipidemia, and atherosclerosis in no distant future. 

PMID- 24563100
TI  - Comparison of pollination and defensive buzzes in bumblebees indicates species
      specific and context-dependent vibrations.
AB  - Bees produce vibrations in many contexts, including for defense and while
      foraging. Buzz pollination is a unique foraging behavior in which bees vibrate
      the anthers of flowers to eject pollen which is then collected and used as food.
      The relationships between buzzing properties and pollen release are well
      understood, but it is less clear to what extent buzzing vibrations vary among
      species, even though such information is crucial to understanding the functional
      relationships between bees and buzz-pollinated plants. Our goals in this study
      were (1) to examine whether pollination buzzes differ from those produced during
      defense, (2) to evaluate the similarity of buzzes between different species of
      bumblebees (Bombus spp.), and (3) to determine if body size affects the
      expression of buzzing properties. We found that relative peak amplitude, peak
      frequency, and duration were significantly different between species, but only
      relative peak amplitude differed between pollination and defensive buzzes. There
      were significant interactions between species and buzz type for peak frequency
      and duration, revealing that species differed in their patterns of expression in
      these buzz properties depending on the context. The only parameter affected by
      body size was duration, with larger bees producing shorter buzzes. Our findings
      suggest that although pollination and defensive buzzes differ in some properties,
      variability in buzz structure also exhibits a marked species-specific component.
      Species differences in pollination buzzes may have important implications for
      foraging preferences in bumblebees, especially if bees select flowers best
      matched to release pollen for their specific buzzing characteristics. 

PMID- 24563101
TI  - Response to: research integrity: the experience of a doubting Thomas.

PMID- 24563102
TI  - Pregnancy-induced hypertension is accompanied by decreased number of circulating
      endothelial cells and circulating endothelial progenitor cells.
AB  - Maternal endothelial dysfunction is one of the main features of pregnancy-induced
      hypertension (PIH). It is generally accepted that circulating endothelial cells
      (CECs) and endothelial progenitor cells (EPCs) reflect the state of the
      endothelium, its injury and/or repair possibilities. The objective of this study
      was to determine whether the CECs and EPCs numbers in the circulation of women
      with PIH reflect the presence of this pathology. Peripheral blood cells of PIH
      and normotensive pregnant women were labeled with specific monoclonal antibodies.
      For CECs evaluation, samples were labeled with anti-CD31 and anti-CD45
      antibodies; for EPCs with anti-VEGFR2/KDR and anti-CD34 antibodies. Cells were
      quantified by flow cytometry. The levels of both CECs (CD31(+), CD45(-)) and EPCs
      (CD34(+), VEGFR2/KDR(+)) in the peripheral blood of women with PIH were
      significantly lower compared with those of control pregnant women with normal
      blood pressure level. Lowered accessibility of maternal CECs and EPCs may
      diminish general regenerative potential of the patient endothelia, contributing
      to PIH symptoms and to the risk of subsequent coronary and arterial disease. 

PMID- 24563103
TI  - Screening for substance abuse risk in cancer patients using the Opioid Risk Tool
      and urine drug screen.
AB  - PURPOSE: The use of opioids for management of cancer-related pain has increased
      significantly and has been associated with a substantial rise in rates of
      substance abuse and diversion. There is a paucity of data not only on the
      prevalence of substance abuse in cancer patients, but also for issues of drug use
      and diversion in family caregivers. This study aimed to evaluate the frequency of
      risk factors for substance abuse and diversion, and abnormal urine drug screens
      in cancer patients receiving palliative care. METHODS: A retrospective chart
      review was performed for patients with cancer who were seen in the University of
      Virginia Palliative Care Clinic during the month of September 2012. We evaluated
      Opioid Risk Tool variables and total scores, insurance status, and urine drug
      screen results. RESULTS: Of the 114 cancer patients seen in September 2012, the
      mean Opioid Risk Tool score was 3.79, with 43% of patients defined as medium to
      high risk. Age (16-45 years old, 23%) and a personal history of alcohol (23%) or
      illicit drugs (21%) were the most common risk factors identified. We obtained a
      urine drug screen on 40% of patients, noting abnormal findings in 45.65%.
      CONCLUSIONS: Opioids are an effective treatment for cancer-related pain, yet
      substantial risk for substance abuse exits in the cancer population. Screening
      tools, such as the Opioid Risk Tool, should be used as part of a complete patient
      assessment to balance risk with appropriate relief of suffering.

PMID- 24563104
TI  - Iodine nutritional status among neonates in the Solan district, Himachal Pradesh,
      India.
AB  - Iodine nutrition status amongst neonates can be assessed by estimating thyroid
      stimulating hormone (TSH). According to WHO, if more than 3 % of the neonates
      have TSH levels of 5 mlU/l and more in a population, it indicates presence of
      iodine deficiency (ID). Iodine deficiency is an endemic health problem in Solan
      district, Himachal Pradesh (HP) state. ID leads to mental retardation, deaf
      mutism, squint, dwarfism, spastic diplegia, neurological defects and congenital
      anomalies. The aim is to determine iodine nutrition status of neonates of Solan
      district. In Solan district, six hospitals/community health centers providing
      obstetric services and conducting more than 100 deliveries per annum were
      identified and enlisted. Two hospitals were selected keeping in view of
      operational feasibility. A total of 683 umbilical cord blood samples of neonates
      were collected on filter paper and analyzed for TSH. It was found that 63.2 % of
      the neonates had TSH levels of more than 5 mlU/l indicating iodine deficiency in
      the Solan district. Iodine deficiency was a public health problem in Solan
      district, HP.

PMID- 24563105
TI  - Laparoscopic sleeve gastrectomy for late adolescent population.
AB  - BACKGROUND: Morbid obesity prevalence is rapidly increasing among adolescents
      worldwide. Evidence is mounting that bariatric surgery is the only reliable
      method for substantial and sustainable weight loss; however, the debate continues
      with regard to the optimal surgical procedure for adolescents and to the age
      limit when bariatric surgery should be proposed. METHODS: A retrospective
      multicenter review included all late adolescent patients (<20 years old) who
      underwent sleeve gastrectomy from 2005 to 2012 in three French bariatric centers:
      Montpellier University Hospital, Casamance Private Hospital, and Noumea Regional
      Hospital. Collected data included age, sex, body mass index (BMI), intraoperative
      complications, length of hospital stay, operative morbidity, the need for
      reoperation, and percentage of excess weight loss (% EWL) at 6 months, 1 year,
      and 2 years postoperatively. RESULTS: A total of 61 adolescent patients have
      undergone sleeve gastrectomy. Of these, 42 were women and 19 were men. The mean
      preoperative weight was 132.8 kg (range 90-217 kg) with a BMI of 46.7 (range 35.5
      68.7). Seventeen patients (27.9%) were superobese (BMI > 50), and seven patients
      (11.5%) were supersuperobese (BMI > 60). All the procedures were performed by
      laparoscopy with no intraoperative complications. The mean hospital stay was 4.6
      days. Four major complications were recorded: one staple line leak, two
      hematomas, and one case of pneumonia. No mortality was recorded. The % EWL at 6
      months, 1 year, and 2 years postoperatively was 48.1% (+/-17.9%), 66.7% (+/
      19.5%), and 78.4% (+/-16.8%), respectively, for a follow-up of 93.4, 81.9, and
      52.4%, respectively. There were 18 patients (29.5%) with identified comorbid
      conditions: 10 cases of sleep apnea, 7 cases of hypertension, and 1 case of type
      2 diabetes, with a resolution rate of 77.8%. CONCLUSIONS: Laparoscopic sleeve
      gastrectomy may be advantageous for this age group, since it involves neither
      foreign body placement nor lifelong malabsorption. Laparoscopic sleeve
      gastrectomy represents an attractive bariatric procedure for adolescent patients,
      more efficient than gastric banding and with less morbidity compared to gastric
      bypass.

PMID- 24563106
TI  - Validating the alterable weight loss (AWL) metric with 2-year weight loss outcome
      of 500 patients after gastric bypass.
AB  - BACKGROUND: Percentage alterable weight loss (AWL) is the only known weight loss
      metric independent of the initial body mass index (BMI), a unique feature ideal
      for use in weight loss research. AWL was not yet validated. The aim of the study
      is to validate the AWL metric and to confirm advantages over the excess weight
      loss (EWL) metric. METHODS: AWL is tested with 2-year weight loss results of all
      primary laparoscopic Roux-en-Y gastric bypass patients operated in our hospital.
      Nadir results of patients with higher and lower initial BMI are compared (Mann
      Whitney; p < 0.05) using outcome metrics BMI, percentage weight loss (WL), EWL,
      and AWL, for the whole group, for each gender, and for <40 and >=40 years
      separately. RESULTS: Five-hundred patients (401 female) out of 508 (98.4 %) had 2
      year follow-up. Of all four metrics, only AWL rendered results not significantly
      influenced by initial BMI. The AWL outcome is initial BMI independent for both
      genders and age-groups. Results also confirm that women and younger patients had
      significantly higher AWL outcome. CONCLUSION: The recently developed AWL metric,
      defined as 100% * (initialBMI - BMI) / (initialBMI - 13), is now validated. In
      contrast to the well-known outcome metrics BMI, EWL, and WL, the AWL metric is
      independent of the initial BMI. It should replace the misleading EWL metric for
      comparing weight loss results in bariatric research and for expressing the
      effectiveness of bariatric procedures. This effectiveness does not act on the
      total body mass, or on the excess part, but on the alterable part, defined as BMI
      minus 13 kg/m(2) for all adult patients, female, male, young, and old.

PMID- 24563107
TI  - Tibial tubercle osteotomy with absorbable suture fixation in revision total knee
      arthroplasty: a report of 23 cases.
AB  - OBJECTIVE: Tibial tubercle osteotomy (TTO) is a well-known technique for
      improving exposure in difficult total knee arthroplasty (TKA). We have performed
      23 revision TKAs with TTO. The tibial tubercle was fixated with only absorbable
      sutures afterwards. The aim of this study is to report on the clinical results
      and complications of this procedure. METHODS: We retrospectively evaluated 23
      patients (mean age 69.6 years, range 43-84 years) who underwent TTO with only
      absorbable suture fixation. Clinic charts were reviewed to identify any
      complications that occurred. Obvious proximal migration and union of the tibial
      tubercle was evaluated on the postoperative radiographs. Knee Society scores and
      SF-36 were assigned at latest follow-up. RESULTS: The mean follow-up was 16.1
      months (1-43). Two patients died of causes unrelated to surgery. In one case a
      fracture of the TTO occurred. No obvious migration of the osteotomy was detected.
      In two cases there was partial consolidation of the osteotomy, but without
      clinical consequences of pain or extension lag. In five patients a tibial plateau
      fracture occurred intraoperative which allowed partial weight bearing during 6
      weeks. These fractures were not related to the surgical technique of the TTO. In
      15 out of 23 patients a Knee Society Score could be assigned. The mean total knee
      score (maximum 200 points) after revision was 99.5 (17-166) (clinical KSS 52.1,
      functional KSS 47.3) at latest follow-up. SF-36 scores could be assigned to 16
      patients; the mean SF-36 (maximum 100) was 88 (range 74-98). CONCLUSION: Tibial
      tubercle osteotomy with only absorbable suture fixation is a reliable and simple
      method of fixation and provides adequate stability. It is a straightforward
      surgical technique which is less time-consuming and expensive compared with screw
      and cerclage wire fixation and no hardware removal will be necessary. Therefore,
      this method is a beneficial technique for the enhancement of surgical exposure in
      difficult revision TKA.

PMID- 24563109
TI  - Reliability and validity of the Iranian version of the QAPACE in adolescents.
AB  - PURPOSE: The aim of this study was to determine the reliability and validity of
      the Iranian version of the Quantification de l'Activite Physique en Altitude Chez
      les Enfants (QAPACE) in adolescents. METHODS: After linguistic validation, the
      Iranian version of the QAPACE was completed by 359 (52.4 % girls) schoolchildren,
      aged 15-18 years. Test-retest reliability of the questionnaire was determined by
      intraclass correlation coefficients (ICCs). For validation purposes, two methods
      were used for (1) the correlation between VO2peak and the DEE and (2) known-group
      validity, which was examined by comparing the normal weight adolescents and those
      who were overweight/obese. RESULTS: ICCs for test-retest ranged from 0.79 to
      0.98. The mean scores in test-retest surveys for total score and all of the
      subscores were significant (p < 0.05). Sex-specific analysis showed a significant
      correlation between VO2peak and DEE over 12-month, school, and vacation periods
      in girls (p < 0.05). The mean values for all activities except for
      transportation, other activities in school, personal artistic activities, sport
      competition, and home activities were significantly lower in overweight/obese
      group than normal group. CONCLUSION: Our results support the initial reliability
      and validity of the Iranian version of QAPACE as a daily physical activity
      measure in adolescents.

PMID- 24563110
TI  - Assessment of score- and Rasch-based methods for group comparison of longitudinal
      patient-reported outcomes with intermittent missing data (informative and non
      informative).
AB  - PURPOSE: The purpose of this study was to identify the most adequate strategy for
      group comparison of longitudinal patient-reported outcomes in the presence of
      possibly informative intermittent missing data. Models coming from classical test
      theory (CTT) and item response theory (IRT) were compared. METHODS: Two groups of
      patients' responses to dichotomous items with three times of assessment were
      simulated. Different cases were considered: presence or absence of a group effect
      and/or a time effect, a total of 100 or 200 patients, 4 or 7 items and two
      different values for the correlation coefficient of the latent trait between two
      consecutive times (0.4 or 0.9). Cases including informative and non-informative
      intermittent missing data were compared at different rates (15, 30 %). These
      simulated data were analyzed with CTT using score and mixed model (SM) and with
      IRT using longitudinal Rasch mixed model (LRM). The type I error, the power and
      the bias of the group effect estimations were compared between the two methods.
      RESULTS: This study showed that LRM performs better than SM. When the rate of
      missing data rose to 30 %, estimations were biased with SM mainly for informative
      missing data. Otherwise, LRM and SM methods were comparable concerning biases.
      However, regardless of the rate of intermittent missing data, power of LRM was
      higher compared to power of SM. CONCLUSIONS: In conclusion, LRM should be favored
      when the rate of missing data is higher than 15 %. For other cases, SM and LRM
      provide similar results.

PMID- 24563111
TI  - Psychometric properties of the eight-item modified Medical Outcomes Study Social
      Support Survey based on Spanish outpatients.
AB  - PURPOSE: The aim of this study was to examine the psychometric properties of the
      modified Medical Outcomes Study Social Support Survey (mMOS-SS) in a primary
      healthcare setting (PHCS). METHODS: A cross-sectional descriptive study was
      carried out with Spanish outpatients (N = 903) from a PHCS. Subjects responded to
      the first eight items of the classic Medical Outcomes Study-Social Support Survey
      (MOS-SS), in effect the mMOS-SS, and immediately proceeded to give answers to the
      rest of the scale. Also, sociodemographic, self-reported health status and
      mood/anxiety disorders data were collected. Factor structure was analyzed using
      exploratory and confirmatory analysis, internal reliability was determined by
      Cronbach's standardized alpha, and consistency was evaluated by item-to-total
      score correlations. Evidences of validity were assessed by Spearman's rank
      correlations, and using the Mann-Whitney test or Kruskal-Wallis test as
      appropriate, of differences between the mMOS-SS and the MOS-SS. RESULTS: Mean
      scores for the MOS-SS (mean = 4.26, SD = 0.78) and mMOS-SS (mean = 4.34, SD =
      0.74) are similar. Cronbach's alpha was 0.96 and 0.91, for the MOS-SS and mMOS
      SS, respectively. Item-to-total score correlations of the MOS-SS and mMOS-SS are
      >=0.64 and >=0.70, respectively. Exploratory factor analysis (EFA) [56.63%
      variance, KMO=0.904; chi2=4396.27], and confirmatory factor analysis (CFA)
      [CFI=0.95; NNFI(TLI)=0.97; SRMR=0.05; chi2=296.81; RMSEA=0.17] showed a one
      factor structure. CONCLUSIONS: Psychometric properties of the Spanish version of
      the mMOS-SS in outpatients attending a PHCS are adequate. Factor analysis
      confirmed a one-factor model with acceptable fit indices.

PMID- 24563112
TI  - Phytochemistry and biological activity of Spanish Citrus fruits.
AB  - The evaluation of the potential inhibitory activity on alpha-glucosidase and
      pancreatic lipase by Citrus spp. fruits of Spanish origin (lemon, orange,
      grapefruit, lime, and mandarin) together with the evaluation of their
      phytochemical content and antioxidant capacity (DPPH, ORACFL, ABTS(+), FRAP and
      O2(-)) aiming for new applications of the fruits in nutrition and health was
      carried out. As far as we are aware, the presence of 3-O-caffeoylferuoylquinic
      acid and two hydrated feruloylquinic acids in orange and the presence of 3,5
      diferuoylquinic acid in grapefruit have been reported for the first time.
      Although grapefruit showed higher contents of phytochemicals such as flavanones
      and vitamin C, lemon and lime showed higher potential for inhibitory effects on
      lipase, and lime also showed the best results for in vitro alpha-glucosidase
      inhibition. On the other hand, higher antioxidant capacity was reported for
      grapefruit, lemon and lime, which correlated well with their phytochemical
      composition. Based on the results, it could be concluded that Citrus fruits are
      of great value for nutrition and treatment of diet-related diseases such as
      obesity and diabetes, and consequently, a new field of interest in the food
      industry regarding new bioactive ingredients would be considered.

PMID- 24563114
TI  - [The social relegation of widows living with HIV in the time of ART in Senegal].
AB  - While prolonged widowhood is unusual in Senegalese society, some women living
      with HIV receiving antiretroviral therapy for ten years remained widows. Are they
      maintained in this situation for refusing or being unable to remarry? To
      understand the conditions and the reasons for this lack of "matrimonial
      normalization", a qualitative interview study was conducted in Dakar with 31
      widows. Their living conditions are mostly marked by economic difficulties,
      dependence on host families, and responsibilities visa-vis their children. They
      refuse to remarry, regret not being able to, or wish to without success, despite
      the existence locally of social forms of marital union that would respond to
      their situation. The refusal to disclose their HIV status combined with self
      stigma prevent them from improving their condition. This form of social
      vulnerability that remains beyond the restoration of health is ignored by public
      policy and HIV/AIDS community based organizations claims. It should be
      acknowledged and considered for defending PLWAs' rights. 

PMID- 24563116
TI  - Antitumor effect of TRAIL on oral squamous cell carcinoma using magnetic
      nanoparticle-mediated gene expression.
AB  - We developed a new magnetic nanovector to improve the efficiency and targeting of
      transgene therapy for oral squamous cell carcinoma (OSCC). Positively charged
      polymer PEI-modified Fe(3)O(4) magnetic nanoparticles were tested as gene
      transfer vectors in the presence of a magnetic field. The Fe(3)O(4) nanoparticles
      were prepared by a co-precipitation method and had good dispersibility in water.
      These nanoparticles modified by PEI were combined with negatively charged pACTERT
      EGFP via electrostatic interaction. The transfection efficiency of the magnetic
      nano-gene vector with the magnetic field was determined by a fluorescence
      inverted microscope and flow cytometry. The results showed significant
      improvement compared with the control group (p < 0.05). The magnetic complexes
      also exhibited up to 6-times higher transfection efficiency compared with
      commonly used PEI or lipofectin. On the basis of these results, the antitumor
      effect with suicide gene therapy using pACTERT-TRAIL in vitro and vivo was
      evaluated. In vitro apoptosis was determined with the Annexin V-FITC Apoptosis
      Detection Kit. The results suggested that PEI-modified Fe(3)O(4) nanoparticles
      could mediate the killing of Tca83 cells. Furthermore, treatment with pACTERT
      TRAIL delivered by magnetic nanoparticles showed a significant cytostatic effect
      through the induction of apoptosis in a xenograft model. This indicates that
      magnetic nano-gene vectors could improve the transgene efficiency for Tca83 cells
      and could exhibit antitumor functions with the plasmid pACTERT-TRAIL. This may be
      a new way to treat OSCC.

PMID- 24563118
TI  - Commentary: current perspectives on the aggregation of protein drugs.

PMID- 24563115
TI  - Impact of geographic and transportation-related barriers on HIV outcomes in sub
      Saharan Africa: a systematic review.
AB  - Difficulty obtaining reliable transportation to clinic is frequently cited as a
      barrier to HIV care in sub-Saharan Africa (SSA). Numerous studies have sought to
      characterize the impact of geographic and transportation-related barriers on HIV
      outcomes in SSA, but to date there has been no systematic attempt to summarize
      these findings. In this systematic review, we summarized this body of literature.
      We searched for studies conducted in SSA examining the following outcomes in the
      HIV care continuum: (1) voluntary counseling and testing, (2) pre-antiretroviral
      therapy (ART) linkage to care, (3) loss to follow-up and mortality, and (4) ART
      adherence and/or viral suppression. We identified 34 studies containing 52 unique
      estimates of association between a geographic or transportation-related barrier
      and an HIV outcome. There was an inverse effect in 23 estimates (44 %), a null
      association in 26 (50 %), and a paradoxical beneficial impact in 3 (6 %). We
      conclude that geographic and transportation-related barriers are associated with
      poor outcomes across the continuum of HIV care.

PMID- 24563119
TI  - Vision screening of older drivers for preventing road traffic injuries and
      fatalities.
AB  - BACKGROUND: Demographic data in North America, Europe, Asia, Australia and New
      Zealand suggest a rapid growth in the number of persons over the age of 65 years
      as the baby boomer generation passes retirement age. As older adults make up an
      increasing proportion of the population, they are an important consideration when
      designing future evidence-based traffic safety policies, particularly those that
      lead to restrictions or cessation of driving. Research has shown that cessation
      of driving among older drivers can lead to negative emotional consequences such
      as depression and loss of independence. Older adults who continue to drive tend
      to do so less frequently than other demographic groups and are more likely to be
      involved in a road traffic crash, possibly due to what is termed the "low mileage
      bias". Available research suggests that older driver crash risk estimates based
      on traditional exposure measures are prone to bias. When annual driving distances
      are taken in to consideration, older drivers with low driving distances have an
      increased crash risk, while those with average or high driving distances tend to
      be safer drivers when compared to other age groups. In addition, older drivers
      with lower distance driving tend to drive in urban areas which, due to more
      complex and demanding traffic patterns, tend to be more accident-prone. Failure
      to control for actual annual driving distances and driving locations among older
      drivers is referred to as "low mileage bias" in older driver mobility research.
      It is also important to note that older drivers are more vulnerable to serious
      injury and death in the event of a traffic crash due to changes in physiology
      associated with normal ageing. Vision, cognition, and motor functions or skills
      (e.g., strength, co-ordination, and flexibility) are three key domains required
      for safe driving. To drive safely, an individual needs to be able to see road
      signs, road side objects, traffic lights, roadway markings, other vulnerable road
      users, and other vehicles on the road, among many other cues-all while moving,
      and under varying light and weather conditions. It is equally important that
      drivers must have appropriate peripheral vision to monitor objects and movement
      to identify possible threats in the driving environment. It is, therefore, not
      surprising that there is agreement among researchers that vision plays a
      significant role in driving performance. Several age-related processes/conditions
      impair vision, thus it follows that vision testing of older drivers is an
      important road safety issue. The components of visual function essential for
      driving are acuity, static acuity, dynamic acuity, visual fields, visual
      attention, depth perception, and contrast sensitivity. These indices are
      typically not fully assessed by licensing agencies. Also, current vision
      screening regulations and cut-off values required to pass a licensing test vary
      from country to country. Although there is a clear need to develop evidence-based
      and validated tools for vision screening for driving, the effectiveness of
      existing vision screening tools remains unclear. This represents an important and
      highly warranted initiative to increase road safety worldwide. OBJECTIVES: To
      assess the effects of vision screening interventions for older drivers to prevent
      road traffic injuries and fatalities. SEARCH METHODS: For the update of this
      review we searched the Cochrane Injuries Group's Specialised Register, the
      Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library),
      MEDLINE (OvidSP), Embase (OvidSP), PsycINFO (OvidSP) and ISI Web of Science:
      (CPCI-S & SSCI). The searches were conducted up to 26 September 2013. SELECTION
      CRITERIA: Randomised controlled trials (RCTs) and controlled before and after
      studies comparing vision screening to non-screening of drivers aged 55 years and
      older, and which assessed the effect on road traffic crashes, injuries,
      fatalities and any involvement in traffic law violations. DATA COLLECTION AND
      ANALYSIS: Two review authors independently screened the reference lists for
      eligible articles and independently assessed the articles for inclusion against
      the criteria. If suitable trials had been available, two review authors would
      have independently extracted data using a standardised extraction form. MAIN
      RESULTS: No studies were found that met the inclusion criteria for this review.
      AUTHORS' CONCLUSIONS: Most countries require a vision screening test for the
      renewal of an individual's driver's licence. There is, however, lack of
      methodologically sound studies to assess the effects of vision screening tests on
      subsequent motor vehicle crash reduction. There is a need to develop valid and
      reliable tools of vision screening that can predict driving performance.

PMID- 24563117
TI  - Decreased response of interneurons in the medial prefrontal cortex to 5-HT1A
      receptor activation in the rat 6-hydroxydopamine Parkinson model.
AB  - This study examined the response of interneurons in the medial prefrontal cortex
      (mPFC) to 5-HT1A receptor agonist 8-OH-DPAT and change in expression of 5-HT1A
      receptor on glutamate decarboxylase 67 (GAD67)-positive neurons in rats with 6
      hydroxydopamine (6-OHDA) lesions of the substantia nigra pars compacta (SNc).
      Systemic administration of 5-HT1A receptor agonist 8-OH-DPAT dose-dependently
      inhibited the firing rate of the interneurons at all doses tested in sham
      operated rats. In 6-OHDA-lesioned rats, 8-OH-DPAT, at the same doses, also
      inhibited the firing rate of the interneurons, whereas the inhibition was
      significant only at a high cumulative dose. Furthermore, injection of 8-OH-DPAT
      into the mPFC inhibited the interneurons in sham-operated rats, while having no
      effect on firing rate of the interneurons in 6-OHDA-lesioned rats. In contrast to
      sham-operated rats, SNc lesion reduced the expression of 5-HT1A receptor on GAD67
      positive neurons in the prelimbic cortex, a sub-region of the mPFC. Our results
      indicate that degeneration of the nigrostriatal pathway leads to decreased
      response of mPFC interneurons to 5-HT1A receptor activation, which attributes to
      the down-regulation of 5-HT1A receptor expression in these interneurons.

PMID- 24563120
TI  - Improving the efficiency of isolated microspore culture in six-row spring barley:
      I-optimization of key physical factors.
AB  - An improved isolated microspore culture protocol alleviating the recalcitrance
      typically observed in six-row spring barley was developed by optimizing four key
      physical factors to increase embryogenesis and reduce albinism. Doubled haploid
      (DH) plants are completely homozygous individuals that can be generated in just a
      few months via androgenesis in vitro. DHs are useful tools in genetic research
      and in plant breeding. Isolated microspore culture (IMC) is the most efficient
      way to produce DHs, but a strong genotype dependency imposes limitations to its
      wide application. Six-row, spring barley genotypes are considered as particularly
      recalcitrant due to a low frequency of embryogenesis and a high rate of albinism.
      Seeking to develop an efficient IMC protocol for this type of barley, we explored
      four important factors: (1) the harvest stage of immature spikes, (2) the type of
      pretreatment applied, (3) the osmotic potential in the induction medium, and (4)
      the plating density of microspores. This work was first performed using four
      barley genotypes: two typical six-row spring cultivars (ACCA and Leger), a two
      row spring (Gobernadora) and a two-row winter (Igri) cultivar. First, by
      optimizing the harvest stage for each genotype we obtained a twofold to fourfold
      increase in the yield of embryogenic microspores. Second, two pretreatments (0.3
      M mannitol for 2 days, or a combination of cold and heat over 15 days) both
      performed significantly better than the commonly used cold pretreatment (28 days
      at 4  degrees C). Third, an induction medium-containing mannitol (32 g/l) doubled
      green plant regeneration. Fourth, a plating density of 10(6) microspores/ml
      yielded the highest number of green regenerated plants. Our most important
      findings were then confirmed using sets of F1s from a six-row, spring-type
      breeding program.

PMID- 24563121
TI  - Laying date and polygyny as determinants of annual reproductive success in male
      collared flycatchers (Ficedula albicollis): a long-term study.
AB  - Annual reproductive success (ARS) is one of the main components of lifetime
      reproductive success, a reliable measure of individual fitness. Previous studies
      often dealt with ARS and variables potentially affecting it. Among them, long
      term studies that consider multiple factors at the same time are particularly
      important in understanding the adaptive value of different phenotypes. Here, we
      used an 18-year dataset to quantify the ARS of male collared flycatchers
      (Ficedula albicollis) on the basis of recruited offspring. We simultaneously
      assessed the effect of start of breeding, age, polygyny, body size and the
      expression of forehead patch (a sexually selected trait). The success of early
      breeding individuals was appreciably higher than late birds; however, breeding
      too early was also disadvantaged, and males that bred around the yearly median
      breeding date had the highest ARS. Polygynous males were more successful in years
      with good food supply, while in years with low food availability, they did not
      produce more recruits than monogamous males. The age of males, their forehead
      patch size and body size did not affect the number of recruits. Our findings
      support the importance of breeding date and suggest stabilizing selection on it
      in the long term. We also show that polygyny is not always advantageous for
      males, and its fitness pay-off may depend on environmental quality. 

PMID- 24563123
TI  - Diagnostic accuracy for macroscopic classification of nodular hepatocellular
      carcinoma: comparison of gadolinium ethoxybenzyl diethylenetriamine pentaacetic
      acid-enhanced magnetic resonance imaging and angiography-assisted computed
      tomography.
AB  - BACKGROUND: The macroscopic type of hepatocellular carcinoma (HCC) is a predictor
      of prognosis. We clarified the diagnostic value of gadolinium ethoxybenzyl
      diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance
      imaging (MRI) in the macroscopic classification of nodular hepatocellular
      carcinoma (HCC) as compared to angiography-assisted computed tomography (CT).
      METHODS: A total of 71 surgically resected nodular HCCs with a maximum diameter
      of <=5 cm were investigated. HCCs were evaluated preoperatively using Gd-EOB-DTPA
      enhanced MRI and angiography-assisted CT. HCCs were pathologically classified as
      simple nodular (SN), SN with extranodular growth (SN-EG), or confluent
      multinodular (CMN). SN-EG and CMN were grouped as non-SN. Five readers
      independently reviewed the images using a five-point scale. We examined the
      accuracy of both imaging modalities in differentiating between SN and non-SN HCC.
      RESULTS: Overall, the area under the receiver operating characteristic curve (A z
      ) for the diagnosis of non-SN did not differ between Gd-EOB-DTPA-enhanced MRI and
      angiography-assisted CT [0.879 (95% confidence interval (CI), 0.779-0.937) and
      0.845 (95% CI, 0.723-0.919), respectively]. For HCCs >2 cm, the A z for Gd-EOB
      DTPA-enhanced MRI was greater than 0.9. The sensitivity, specificity, and
      accuracy of Gd-EOB-DTPA-enhanced MRI for identifying non-SN were equal to or
      higher than values with angiography-assisted CT in all three categories (all
      tumors, <=2 cm, and >2 cm), but the differences were not statistically
      significant. CONCLUSIONS: Using Gd-EOB-DTPA-enhanced MRI to assess the
      macroscopic findings in nodular HCC was equal or superior to using angiography
      assisted CT.

PMID- 24563137
TI  - Life span history of non-fatal suicidal behaviours in a large sample of general
      practitioners' patients: data from Rovigo, Northern Italy.
AB  - A survey about history of non-fatal suicidal behaviour was performed on 1,171
      subjects in the waiting room of general practitioners' practices in the territory
      of Rovigo (Northern Italy). The mean age of interviewed subjects was 52.9 +/-
      17.0, with a majority of female individuals. Two and two percent admitted
      previous experience of non-suicidal self-injury, 4.7 % admitted having had
      serious suicidal thoughts/plans, and 1.8 % reported at least one suicide attempt.
      Compared to the rest of the sample, people with history of suicidal behaviours
      resulted to be of younger age (p < .05), whilst their level of well-being was
      poorer (p < .001). When compared to the results of the Italian arm of the
      European Study of the Epidemiology of Mental Disorders, carried out on general
      population samples, the present study produces higher rates of suicidality,
      despite the much higher mean age of the interviewed subjects compared to the
      general population. 

PMID- 24563138
TI  - Using Internet to recruit immigrants with language and culture barriers for
      tobacco and alcohol use screening: a study among Brazilians.
AB  - Limited English proficient (LEP) individuals face disparities in accessing
      substance abuse treatment, but little is known on how to reach this population.
      This study aimed to test online recruitment methods for tobacco and alcohol
      screening among LEP Portuguese speakers. The study was advertised in Portuguese
      using Facebook, Google, online newsletters and E-mail. Participants clicked ads
      to consent and access a screening for tobacco and alcohol dependence. Ads yielded
      690 screening responses in 90 days. Respondents had a mean age of 42.7 (SD 12),
      with a higher proportion of women than men, 95% born in Brazil with high levels
      of LEP and low levels of acculturation. Facebook ads yielded 41.4% of responses,
      and were the lowest cost recruitment channel ($8.9, $31.10 and $20.40 per
      respondent, hazardous drinker and smoker, respectively). Online recruitment of
      LEP populations is feasible. Future studies should test similar strategies in
      other LEP groups.

PMID- 24563139
TI  - Review of the genus Eutetrarhynchus Pintner, 1913 (Trypanorhyncha:
      Eutetrarhynchidae), with the description of Eutetrarhynchus beveridgei n. sp.
AB  - The genus Eutetrarhynchus Pintner, 1913 is revised. Eutetrarhynchus beveridgei n.
      sp. is described from the spiral intestine of the dwarf whipray, Himantura walga
      (Muller & Henle) (Myliobatiformes: Dasyatidae), from the South China Sea off the
      Malaysian part of Borneo. The new species is characterised by a slender, elongate
      scolex, two oval bothria, muscular bulbs, retractor muscles inserting at the base
      of the bulbs, and the presence of gland-cells and prebulbar organs. The
      tentacular armature is typical heteroacanthous with heteromorphous hooks.
      Eutetrarhynchus beveridgei n. sp. is allocated to the genus due to its distinct
      segment morphology featuring two internal seminal vesicles and scattered testes
      occupying the complete intervascular space. It differs from congeners in its
      relatively small size, much smaller scolex regions and in the presence of a basal
      armature with a distinct basal swelling. Eutetrarhynchus cortezensis Friggens &
      Duszynski, 2005 is transferred to Dollfusiella Campbell & Beveridge, 1994, as D.
      cortezensis n. comb., on the basis of its segment morphology, with testes in a
      linear arrangement and the absence of internal seminal vesicles. A new generic
      diagnosis and a key for the identification of species of Eutetrarhynchus is
      provided. 

PMID- 24563140
TI  - A new genus and two new nematode species (Drilonematoidea: Ungellidae:
      Synoecneminae) parasitic in two morphs of Drawida ghilarovi Gates, endemic
      earthworm from the Russian Far East.
AB  - Drasico n. g. is erected to accommodate two new species of nematode, Drasico
      nemoralis n. sp. and D. paludigenus n. sp., recovered from coelomic cavities of
      Drawida ghilarovi Gates, endemic earthworms of the Russian Far East. The new
      genus is characterised by the following unique for the Synoecneminae characters:
      apical portion of the head attenuated, cephalic hooks displaced to the base of
      attenuated portion, amphids displaced posterior to cephalic hooks, excretory duct
      short and weak, males possessing several genital papilliform sensilla. The new
      species are differentiated by the size, number and disposition of the male
      genital sensilla (larger and more numerous in D. nemoralis n. sp.); the body
      shape of females (with thinner neck and wider mid-body in D. paludigenus n. sp.)
      and the ovarian tube arranged in transversal folds in D. paludigenus (vs
      longitudinal folds in D. nemoralis n. sp.). Nucleotide sequences of D2-D3
      expansion segment of 28S rDNA for the two new species differed at 13 positions.
      Phylogenetic analysis revealed close relationships of Drasico n. g. with species
      of Siconema Timm, 1966. The host species was represented by two morphs (blue-grey
      forest and tar-black meadow-swamp morph) with intraspecific divergence of 16-17%
      for cytochrome c oxidase subunit 1 (COI) gene, and each host morph was found
      infected by a different nematode species. A co-infection with the plectid
      nematode Creagrocercus drawidae Ivanova & Spiridonov, 2011 was recorded together
      with D. nemoralis n. sp. in the blue-grey forest morph. 

PMID- 24563141
TI  - Patterns of genetic diversity in Hepatozoon spp. infecting snakes from North
      Africa and the Mediterranean Basin.
AB  - Species of Hepatozoon Miller, 1908 are blood parasites most commonly found in
      snakes but some have been described from all tetrapod groups and a wide variety
      of hematophagous invertebrates. Previous studies have suggested possible
      associations between Hepatozoon spp. found in predators and prey. Particularly,
      some saurophagous snakes from North Africa and the Mediterranean region have been
      found to be infected with Hepatozoon spp. similar to those of various sympatric
      lizard hosts. In this study, we have screened tissue samples of 111 North African
      and Mediterranean snakes, using specific primers for the 18S rRNA gene. In the
      phylogenetic analysis, the newly-generated Hepatozoon spp. sequences grouped
      separately into five main clusters. Three of these clusters were composed by
      Hepatozoon spp. also found in snakes and other reptiles from the Mediterranean
      Basin and North Africa. In the other two clusters, the new sequences were not
      closely related to geographically proximate known sequences. The phylogeny of
      Hepatozoon spp. inferred here was not associated with intermediate host taxonomy
      or geographical distribution. From the other factors that could explain these
      evolutionary patterns, the most likely seems series of intermediate hosts
      providing similar ribotypes of Hepatozoon and a high prevalence of host shifts
      for Hepatozoon spp. This is indicated by ribotypes of high similarity found in
      different reptile families, as well as by divergent ribotypes found in the same
      host species. This potentially low host specificity has profound implications for
      the systematics of Hepatozoon spp. 

PMID- 24563142
TI  - Additional observations on Philometra spp. (Nematoda: Philometridae) in marine
      fishes off Iraq, with the description of two new species.
AB  - Based on light and electron microscopical studies, the following four species of
      Philometra Costa, 1845 (Nematoda: Philometridae) are described from marine fishes
      from off Basrah, southern Iraq (Arabian Gulf): P. brachiri n. sp. (males and
      females) from the ovary of the Oriental sole Brachirus orientalis (Bloch &
      Schneider) (Pleuronectiformes; Soleidae), P. piscaria Moravec & Justine, 2014
      (female) from the ovary of the orange-spotted grouper Epinephelus coioides
      (Hamilton) (Perciformes: Serranidae), P. otolithi Moravec & Manoharan, 2013 (male
      and females) from the ovary of the tigerteeth croaker Otolithes ruber (Bloch &
      Schneider) (Perciformes: Sciaenidae) and P. tricornuta n. sp. (female) from the
      musculature of the caudal peduncle of the greater lizardfish Saurida tumbil
      (Bloch) (Aulopiformes: Synodontidae). Philometra brachiri is mainly characterised
      by the structure of the distal tip of the gubernaculum and the length of the
      spicules (132-135 MUm) in male. Philometra tricornuta is distinguished by the
      presence of three large sclerotised oesophageal teeth and two tandem bulbous
      inflations at the anterior end of oesophagus in female. The female of P. piscaria
      is described for the first time. Philometra brachiri is the first species of this
      genus described from a fish belonging to the family Soleidae. The findings of P.
      piscaria and P. otolithi in Iraqi marine waters represent new geographical
      records. 

PMID- 24563143
TI  - A new species of Rhabdochona Railliet, 1916 (Nematoda: Rhabdochonidae) from
      cyprinid fishes in the Western Ghats Region, India.
AB  - A new nematode species, Rhabdochona (Globochona) puntii n. sp. (Rhabdochonidae),
      is described based on specimens collected from the intestine of the pool barb
      Puntius sophore (Hamilton) and Neolissochilus hexastichus (McClelland) (both
      Cyprinidae) from the Gadhena River, the Western Ghats, Maharashtra State, India.
      The nematode was also found in Wallago attu (Bloch & Schneider) which probably
      acts as postcyclic host. Rhabdochona (Globochona) puntii n. sp. differs markedly
      from its congeners in the body size, the number and distribution of caudal
      papillae, in the presence of an unpaired papilla-like structure on the anterior
      cloacal lip, and in having unusual shape and structure of the terminal crown of
      mucrons. This is the seventh species of the subgenus Globochona Moravec, 1972
      reported from freshwater Indian fishes. 

PMID- 24563144
TI  - A new species of Cucullanus Muller, 1777 (Nematoda: Cucullanidae) parasitic in
      the grey triggerfish Balistes capriscus Gmelin (Osteichthyes: Balistidae) off Rio
      de Janeiro, Brazil.
AB  - Cucullanus brevicaudatus n. sp. (Cucullanidae) is described from the intestine of
      Balistes capriscus Gmelin (Balistidae) off Rio de Janeiro, Brazil. The new
      species can be differentiated from its congeners in the small body length, the
      shape of the gubernaculum, the particular size and morphology of the tail in both
      males and females, the arrangement of the caudal papillae, the narrow oesophageal
      base, and the eggs with rugged shells. In addition, the combination of some
      features, i.e. number of caudal papillae, spicule length, oesophagus/body length
      ratio, host family and geographical distribution, can help to easily distinguish
      the new species from other cucullanids. Considering these features, C.
      brevicaudatus differs from the species assigned to Dichelyne Tornquist, 1931
      which exhibit morphological proximity with Cucullanus Muller, 1777. Regarding the
      life-cycle of cucullanid nematodes, available evidence suggests that some species
      are primarily heteroxenous using invertebrates (i.e. crustaceans, polychaetes) as
      intermediate hosts, but in other a histotrophic phase in the definitive host
      replaces the intermediate host. 

PMID- 24563145
TI  - Phylogenetic affinities and systematic position of Entomelas sylvestris Baker,
      1982 (Nematoda: Rhabdiasidae), a parasite of Breviceps sylvestris FitzSimons
      (Amphibia: Brevicipitidae) in South Africa.
AB  - The genus Entomelas Travassos, 1930 currently includes nine species of rhabdiasid
      nematodes, eight of them parasitic in lizards and only one, Entomelas sylvestris
      Baker, 1982, parasitic in amphibians. Entomelas sylvestris was originally
      described from the Forest Rain Frog Breviceps sylvestris FitzSimons in South
      Africa and was not reported since. It was placed in the genus Entomelas without
      any specific arguments for this taxonomic decision, presumably mainly based on
      details of the buccal capsule morphology. We have found this species in the same
      host in Limpopo province, South Africa. Molecular phylogenetic analysis based on
      the newly-obtained sequence of complete ITS region and partial nuclear large
      ribosomal subunit (28S) gene of E. sylvestris and previously published sequences
      of a variety of other rhabdiasid taxa, has convincingly demonstrated that this
      species does not belong in Entomelas. Instead, it clustered together with the
      members of Rhabdias Stiles & Hassall, 1905 from amphibian hosts. Therefore, we
      transfer E. sylvestris into Rhabdias as Rhabdias sylvestris (Baker, 1982) n.
      comb. In our analysis E. sylvestris appears, albeit with weak support, as a
      basal/sister taxon to the rest of Rhabdias spp. which explains to some extent the
      differences in the buccal capsule morphology between this species and other
      Rhabdias spp. 

PMID- 24563146
TI  - Description of Choleoeimeria duszynskii n. sp. (Apicomplexa: Eimeriidae) from the
      gallbladder of the Middle Eastern short-fingered gecko Stenodactylus doriae
      (Blanford) (Sauria: Gekkonidae) in Saudi Arabia.
AB  - Choleoeimeria duszynskii n. sp. is described from the gallbladder of the Middle
      Eastern short-fingered gecko Stenodactylus doriae (Blanford) from Salasel,
      Central region, Saudi Arabia. Oocysts are ellipsoidal (rarely ovoidal), 23-25 *
      16-18 (24 * 17) MUm, with mean length/width ratio 1.4. Oocyst wall is smooth, bi
      layered, c.1.0 MUm thick. Micropyle, oocyst residuum and polar granule are
      absent. Sporocysts are ellipsoidal, 8-10 * 4-6 (9 * 5) MUm, with a smooth,
      colourless sporocyst wall and mean length/width ratio 1.7. Sporozoites are
      sausage-shaped, with one end slightly pointed, arranged head to tail around
      sporocyst residuum. Refractile bodies and nuclei are not discernible. The
      endogenous development is restricted to the epithelium of the gallbladder and
      bile duct. Meronts are rounded, 12 MUm in diameter, containing up to c.15
      merozoites. Microgamonts are irregular in shape, 22 * 17 MUm, containing a large
      number of microgametes. Macrogamonts are spherical, 17 MUm in diameter, with
      centrally located nucleus and wall-forming bodies at the periphery. 

PMID- 24563147
TI  - Benefits and unexpected artifacts of biplanar digital slot-scanning imaging in
      children.
AB  - Biplanar digital slot-scanning allows for relatively low-dose orthopedic imaging,
      an advantage in imaging children given the growing concerns regarding
      radiosensitivity. We have used this system for approximately 1 year for
      orthopedic imaging of the spine and lower extremities. We have noted advantages
      of using the digital slot-scanning system when compared with computed
      radiographic and standard digital radiographic imaging systems, but we also found
      unexpected but common imaging artifacts that are the direct result of the imaging
      method and that have not been reported. This pictorial essay serves to
      familiarize radiologists with the advantages of the digital slot-scanning system
      as well as imaging artifacts common with this new technology. 

PMID- 24563148
TI  - Functional and radiological outcomes of semi-rigid dynamic lumbar stabilization
      adjacent to single-level fusion after 2 years.
AB  - OBJECTIVE: To prospectively evaluate the functional and radiological outcomes of
      Isobar semi-rigid dynamic posterior stabilization adjacent to single-level fusion
      up to and including 24 months postoperatively. METHOD: A prospective follow-up
      for 24 months of 36 patients who underwent posterior Isobar dynamic stabilization
      due to single-level degenerative lumbar discopathy and instability (DLDI) with
      mild adjacent level degeneration, with collection of functional [visual analog
      scale (VAS) and Oswestry Disability Index (ODI)] and radiological data (resting,
      functional X-rays and MRI). RESULTS: Functional outcomes at 24 months showed
      significant improvement in mean VAS score by 38.9 points (P < 0.01) and ODI by
      22.4 points (P < 0.01). Compared with data preoperatively, disc height at the
      index and adjacent levels and intervertebral angle (IVA) at the index level
      showed a slight decreasing trend at each follow-up (P > 0.05), while IVA at the
      adjacent level showed a slight increasing trend (P > 0.05). Range of motion
      averaged 2.84 degrees  at the index level and remained unchanged at the adjacent
      level (P > 0.05). The mean Pfirrmann score changed from 2.86 preoperatively to
      2.92 at 24 months postoperatively at the index level (P > 0.05), and from 1.92
      preoperatively to 1.96 at 24 months postoperatively at the adjacent level (P >
      0.05). No reoperation, loosening of screws or infection was recorded.
      CONCLUSIONS: Patients with single-level DLDI and mild adjacent level degeneration
      treated with Isobar stabilization show a clinical improvement after 2 years.
      However, disc degeneration at the index and adjacent levels seems to continue
      despite using semi-rigid dynamic stabilization.

PMID- 24563149
TI  - Guided growth of the trochanteric apophysis combined with soft tissue release for
      Legg-Calve-Perthes disease.
AB  - During the initial fragmentation stage of Perthes disease, the principle focus is
      to achieve containment of the femoral head within the acetabulum. Whether by
      bracing, abduction casts, femoral and/or pelvic osteotomy, the goals are to
      maximize the range of hip motion and to avoid incongruity, hoping to avert
      subsequent femoro-acetabular impingement or hinge abduction. A more subtle and
      insidious manifestation of the disease relates to growth disturbance involving
      the femoral neck. We have chosen to tether the greater trochanteric physis,
      combined with a medial soft tissue release, as part of our non-osteotomy
      management strategy for select children with progressive symptomatology and
      related radiographic changes. In addition to providing containment, we feel that
      this strategy addresses potential long-range issues pertaining to limb length and
      abductor mechanics, while avoiding iatrogenic varus deformity caused by
      osteotomy. This is a retrospective review of 12 patients (nine boys, three
      girls), average age 7.3 years old (range 5.3-9.7), who underwent non-osteotomy
      surgery for Perthes disease. An eight-plate was applied to the greater
      trochanteric apophysis at the time of arthrogram, open adductor and iliopsoas
      tenotomy, and Petrie cast application. We compared clinical and radiographic
      findings at the outset to those at an average follow-up of 49 months (range 14-78
      months). Six plates were subsequently removed; the others remain in situ. Eleven
      of twelve patients experienced improvement in pain, and alleviation of limp and
      Trendelenburg sign at latest follow-up. The majority had improved or maintained
      range of motion and prevention of trochanteric impingement demonstrated by near
      normalization of abduction. Neck-shaft angles, Shenton's line, extrusion index,
      center edge angles and trochanteric height did not change significantly. One
      patient underwent subsequent trochanteric distalization and no other patients
      have undergone subsequent femoral or periacetabular osteotomies. Leg length
      discrepancy worsened in four patients and was treated with contralateral eight
      plate distal femoral epiphysiodesis. As a group the mean leg length discrepancy
      did not change significantly. There were no perioperative complications. six
      trochanteric plates were subsequently removed after an average of 43.7 months
      (range 28-69) due to irritation of hardware; the others remain in situ, pending
      further growth. We employed open adductor and iliopsoas tenotomy and Petrie cast
      application and guided growth of the greater trochanter as a means of redirecting
      the growth of the common proximal femoral chondroepiphysis. The accrued benefits
      of preventing relative trochanteric overgrowth with a flexible tether are the
      avoidance of iatrogenic varus and weakening of the hip abductors. The goals are
      to preserve abductor strength and avoid trochanteric transfer or
      intertrochanteric osteotomy. 

PMID- 24563150
TI  - Recurrent hemichorea-hemiballism with non-ketotic hyperglycemia.

PMID- 24563151
TI  - An aggressive case of PCR negative varicella zoster virus induced transverse
      myelitis.

PMID- 24563152
TI  - Brevibacillus as a biological tool: a short review.
AB  - The significance of Brevibacillus has been documented scientifically in the
      published literature and commercially in heterologous recombinant protein
      catalogs. Brevibacillus is one of the most widespread genera of Gram-positive
      bacteria, recorded from the diverse environmental habitats. The high growth rate,
      better transformation efficiency by electroporation, availability of shuttle
      vectors, production of negligible amount of extracellular protease, and the
      constitutive expression of heterologous proteins make some strains of this genus
      excellent laboratory models. Regarding biotechnological applications, this genus
      continues to be a source of various enzymes of great biotechnological interest
      due to their ability to biodegrade low density polyethylene, ability to act as a
      candidate bio-control agent, and more recently acknowledged as a tool for the
      overexpression. This article reviews the properties of Brevibacillus spp. as
      better biological tools with varied applications. 

PMID- 24563154
TI  - Eukaryotic microbial communities in hypersaline soils and sediments from the
      alkaline hypersaline Huama Lake as revealed by 454 pyrosequencing.
AB  - In hypersaline ecosystems, microbial assemblages are structurally distinctive and
      play important roles in many microbiological and ecological processes. Here,
      eukaryotic microorganisms in hypersaline samples were investigated by 454
      pyrosequencing of internal transcribed spacer (ITS) gene libraries. In total,
      4,645, 1,677, and 5,912 reads were obtained from ITS libraries of waterlogged
      samples, salt crusts, and saline loess from the alkaline Huama Lake in Shaanxi,
      China. Analyses of pyrosequencing data revealed that the dominant genera were
      Dunaliella, Alternaria and Chlamydomonas, which dominated the microbial
      assemblages in the waterlogged sediments, the salt crusts and the saline loess
      from the lake banks, respectively. The various infrequent species were not
      commonly shared by the three types of samples, demonstrating that the eukaryotic
      microbial compositions of the different environments were distinct. However, the
      micro-eukaryotic assemblages associated with similar environmental conditions
      shared some components and were phylogenetically related. The eukaryotic
      microbial community composition was correlated with the pH value of the site (p =
      0.001; r(2) = 0.99), but not with the concentration of total nitrogen or the
      inorganic ions investigated in this study. The results of this study demonstrated
      that the hypersaline ecosystems hosted surprisingly diverse eukaryotic microbial
      community. 

PMID- 24563157
TI  - A critical review of the history of low- to moderate-intensity steady-state VO2
      kinetics.
AB  - Research into the rate of whole-body oxygen consumption (VO2) kinetics during
      exercise increments to low- to moderate-intensity steady-state exercise was
      originally based on the theory of linear first-order VO2 kinetics, implying that
      the VO2 response to steady-state exercise increments is a mono-exponential
      response of the same time constant (tau, tau) across all steady-state
      intensities. Despite the acceptance of this theory for more than 30 years, early
      research from the 1980s documented an increasing tau with increasing steady-state
      exercise intensity, and recent research has confirmed such results. Today, such
      evidence has led to retraction of the theory of linear first-order VO2 kinetics.
      This history, revealing the premature acceptance of a theory, and subsequent
      scientific investigation using improved research design, instrumentation and data
      processing, has important implications for the fragility of scientific theories
      and the need for continual testing of theories in the search for facts and not
      prematurely accepted constructs. This review provides historical evidence for a
      critical reappraisal of the theory of linear first-order VO2 kinetics and
      presents data to show the need for changes in the data-processing 'standards' of
      the discipline to improve measurement of instantaneous VO2 kinetics and the time
      to steady state. For example, to date, no study of VO2 kinetics has quantified
      and statistically analysed the time to steady state. Furthermore, the instability
      of tau across different exercise increments, and for the same increment from
      different baseline VO2 demand, prevents tau from being a valid measure of VO2
      kinetics for different exercise conditions. The concept of quantifying kinetics
      from a total non-linear response, when no other field of kinetics pursues this
      methodology, also raises concern for the methods and models used to interpret
      steady-state VO2 kinetics. 

PMID- 24563158
TI  - Training readers to improve their accuracy in grading Crohn's disease activity on
      MRI.
AB  - OBJECTIVES: To prospectively evaluate if training with direct feedback improves
      grading accuracy of inexperienced readers for Crohn's disease activity on
      magnetic resonance imaging (MRI). METHODS: Thirty-one inexperienced readers
      assessed 25 cases as a baseline set. Subsequently, all readers received training
      and assessed 100 cases with direct feedback per case, randomly assigned to four
      sets of 25 cases. The cases in set 4 were identical to the baseline set. Grading
      accuracy, understaging, overstaging, mean reading times and confidence scores
      (scale 0-10) were compared between baseline and set 4, and between the four
      consecutive sets with feedback. Proportions of grading accuracy, understaging and
      overstaging per set were compared using logistic regression analyses. Mean
      reading times and confidence scores were compared by t-tests. RESULTS: Grading
      accuracy increased from 66 % (95 % CI, 56-74 %) at baseline to 75 % (95 % CI, 66
      81 %) in set 4 (P = 0.003). Understaging decreased from 15 % (95 % CI, 9-23 %) to
      7 % (95 % CI, 3-14 %) (P < 0.001). Overstaging did not change significantly (20 %
      vs 19 %). Mean reading time decreased from 6 min 37 s to 4 min 35 s (P < 0.001).
      Mean confidence increased from 6.90 to 7.65 (P < 0.001). During training, overall
      grading accuracy, understaging, mean reading times and confidence scores improved
      gradually. CONCLUSIONS: Inexperienced readers need training with at least 100
      cases to achieve the literature reported grading accuracy of 75 %. KEY POINTS: *
      Most radiologists have limited experience of grading Crohn's disease activity on
      MRI. * Inexperienced readers need training in the MRI assessment of Crohn's
      disease. * Grading accuracy, understaging, reading time and confidence scores
      improved during training. * Radiologists and residents show similar accuracy in
      grading Crohn's disease. * After 100 cases, grading accuracy can be reached as
      reported in the literature.

PMID- 24563159
TI  - The association of haemoglobin A1C levels with the clinical and CT
      characteristics of Klebsiella pneumoniae liver abscesses in patients with
      diabetes mellitus.
AB  - OBJECTIVES: To compare the characteristics of Klebsiella pneumoniae liver
      abscesses (KPLA) in diabetic patients with different levels of glycaemic control.
      METHODS: The institutional review board approved this retrospective study. A
      total of 221 patients with KPLA were included. Clinical features of KPLA were
      compared. We divided the 120 diabetic patients with KPLA into three subgroups
      based on haemoglobin A1C (HbA1C) concentration (good, HbA1C <= 7.0 %; suboptimal,
      7.0 % < HbA1C <= 9.0 %; poor, HbA1C > 9.0 %). In this study, we used a
      semiautomated quantitative method to assess the gas and total abscess volumes in
      KPLA. Statistical analysis was performed with the chi-squared test and one-way
      analysis of variance. RESULTS: The mortality rate did not significantly differ
      between the nondiabetic and diabetic groups. However, patients with poor
      glycaemic control had significantly more complications and therefore a longer
      hospital stay (P < 0.05). In our study, CT and quantitative analyses found that
      patients in the group with poor glycaemic control had a significantly higher
      incidence of gas formation and hepatic venous thrombophlebitis and a higher gas
      to-abscess volume ratio than patients with suboptimal and good glycaemic control
      (P < 0.05). CONCLUSIONS: Diabetic patients with a high HbA1C concentration (>9.0
      %) have an association with hepatic venous thrombophlebitis, gas formation and
      metastatic infection complications associated with KPLA. KEY POINTS: * Poorly
      controlled diabetes is associated with complications in Klebsiella pneumoniae
      liver abscesses. * Hepatic venous thrombosis and gas are important signs of
      metastatic infection. * Hepatic venous thrombophlebitis is associated with 72.7 %
      of metastatic infections.

PMID- 24563160
TI  - Hepatic cysts treated with percutaneous ethanol sclerotherapy: time to extend the
      indications to haemorrhagic cysts and polycystic liver disease.
AB  - OBJECTIVES: To describe the long-term clinical and morphological outcome of
      symptomatic hepatic cysts treated with percutaneous ethanol sclerotherapy (PES).
      METHODS: From December 2003 to September 2011, all patients with hepatic cysts
      undergoing PES with a follow-up after 12 months were included. Evolution of the
      volume of the cysts and clinical and biological data were recorded. Features of
      the cyst were evaluated in each patient: simple, haemorrhagic or developed on
      underlying polycystic liver disease (PCLD). RESULTS: Fifty-eight cysts (median
      volume 666 mL) were treated in 57 patients (52 women, mean age 58 years (18-80)).
      Twenty-two patients (39 %) had simple hepatic cysts, 19 (33 %) had dominant cysts
      on PCLD and 20 had haemorrhagic cysts (34.5 %), including 4 with PCLD. After a
      mean 27.3 months of follow-up, the final median cystic volume was 13.5 mL (p <
      0.0001), and the median reduction in cyst volume was 94 % (58-100 %). Treatment
      was satisfactory in 95 % of the patients (54/57) (symptoms disappeared in 45/57
      (79 %), decreased in 9/57 (16 %)). There was no clinical or morphological
      difference between patients with PCLD, haemorrhagic cysts or simple cysts.
      CONCLUSION: The clinical and morphological efficacy of a single session of PES is
      very high, regardless of the presence of intracystic haemorrhage or underlying
      PCLD. KEY POINTS: * The clinical efficacy of percutaneous ethanol sclerotherapy
      is very high. * Haemorrhagic content should not be a contraindication for
      percutaneous sclerotherapy. * Dominant cysts on polycystic liver disease should
      be treated with PES. * Imaging follow-up should not be performed shortly after
      the procedure.

PMID- 24563161
TI  - Hypocalcemia following thyroid surgery: incidence and risk factors. A
      longitudinal multicenter study comprising 2,631 patients.
AB  - Postoperative hypocalcemia is the most frequent complication of total
      thyroidectomy. It may have a delayed onset, and therefore delays the discharge
      from the hospital, requiring calcium replacement therapy to alleviate clinical
      symptoms. During a 7-month period, 2,631 consecutive patients undergoing primary
      or completion thyroidectomy were prospectively followed up and underwent analysis
      regarding postoperative hypoparathyroidism. Data were prospectively collected by
      questionnaires from 39 Italian endocrine surgery units affiliated to the Italian
      Endocrine Surgery Units Association (Club delle Unita di EndocrinoChirurgia-UEC),
      where thyroid surgery is routinely performed. The incidence of hypoparathyroidism
      was 28.8 % (757 patients), including transient hypocalcemia (27.9 %-734 patients)
      and permanent hypocalcemia (0.9 %-23 patients). The rate of asymptomatic
      hypocalcemia was 70.80 %. The incidence of permanent hypocalcemia was higher in
      the symptomatic hypocalcemia group (7.5 %) than in asymptomatic one (1.5 %).
      Female patients experienced a transient postoperative hypocalcemia more
      frequently than male patients (29.7 and 21.2 %, respectively; p < 0.0001). The
      percentage developing hypocalcemia in patients in which parathyroid glands were
      intraoperatively identified and preserved was higher than in the patients in
      which the identification of parathyroid glands was not achieved (29.2 vs. 18.7 %,
      p < 0.01). This prospective study confirmed the main risk factors for
      postoperative hypocalcemia: thyroid cancer, nodal dissection, and female gender.
      It farther showed that identifying parathyroids has an important role to prevent
      permanent hypocalcemia though with a higher risk of transient hypocalcemia. A
      suitable informed consent should especially emphasize the importance of some
      primary factors in increasing the risk of hypocalcemia after thyroid surgery.

PMID- 24563163
TI  - Two successful pregnancies in a carrier of heterozygous factor V LEIDEN mutation
      with aplasia of the inferior vena cava and a history of proximal deep venous
      thrombosis.

PMID- 24563162
TI  - Cardiorespiratory fitness in older adult women: relationships with serum 25
      hydroxyvitamin D.
AB  - Previous studies suggest that circulating 25(OH)D may favorably influence
      cardiorespiratory fitness and fat oxidation. However, these relationships have
      not been examined in older adult women of different ethnic groups. The objectives
      of this study were to determine whether serum 25(OH)D is related to
      cardiovascular fitness (VO2max) in sedentary women ages >=60 years and to
      determine whether these associations differ between African Americans (AA) and
      European Americans (EA). A secondary aim was to determine whether serum 25(OH)D
      is correlated with respiratory quotient (RQ) during submaximal exercise. This
      cross-sectional analysis included 67 AA and EA women ages 60-74 years. VO2max was
      measured by a modified Bruce graded treadmill protocol, and measurements were
      adjusted for percent fat and lean body mass assessed by air displacement
      plethysmography. Indirect calorimetry was used to measure RQ at rest and during
      four submaximal exercise tests. Fasting blood samples were obtained to quantify
      serum 25(OH)D. Serum 25(OH)D was associated with VO2max (ml/kg LBM/min)
      independent of percent body fat (r = 0.316, p = 0.010). However, subgroup
      analysis revealed that this relationship was specific to AA (r = 0.727, p = 0.005
      for AA; r = 0.064, p = 0.643 for EA). In all subjects combined, 25(OH)D was
      inversely correlated (p < 0.01) with all measures of submaximal RQ. Higher serum
      25(OH)D was associated with greater cardiorespiratory fitness in older adult AA
      women. Among both AA and EA, inverse associations between serum 25(OH)D and RQ
      suggest that women with higher levels of circulating vitamin D also demonstrated
      greater fat oxidation during submaximal exercise.

PMID- 24563165
TI  - Renal epithelial sodium channel is critical for blood pressure maintenance and
      sodium balance in the normal late pregnant rat.
AB  - Normal pregnancy is a state marked by avid sodium retention and plasma volume
      expansion. Insufficient plasma volume expansion results in the compromised
      maternal state of intrauterine growth restriction, which afflicts ~5% of all
      human pregnancies. We have recently shown that renal epithelial sodium channel
      (ENaC) activity in vivo in the late pregnant (LP) rat is increased. To determine
      the importance of the renal versus extrarenal ENaC in sodium retention and blood
      pressure regulation during pregnancy, we have chronically blocked the ENaC
      pharmacologically with daily subcutaneous injections of benzamil and genetically
      using intrarenal transfection of alphaENaC short hairpin RNA. Compared with
      untreated LP control animals, LP rats treated with benzamil retain less sodium
      and have reduced mean arterial blood pressure. Furthermore, LP rats treated with
      benzamil had lower maternal body weight gain. Intrarenal transfection of
      alphaENaC short hairpin RNA versus scrambled small RNA successfully decreased
      renal alphaENaC mRNA expression in LP rats. Intrarenal transfection of alphaENaC
      short hairpin RNA reduced maternal sodium retention, body weight gain and pup
      weight. Redundant physiological systems that protect blood pressure and sodium
      homeostasis were unable to compensate for the loss of ENaC activity in the
      pregnant rat. These findings demonstrate that the renal ENaC is necessary for
      maintaining pregnancy-mediated sodium retention, volume expansion and blood
      pressure regulation. 

PMID- 24563167
TI  - Thoracic ultrasound in children: evidence and drawbacks.

PMID- 24563168
TI  - Parents' perspectives of life challenges experienced by long-term paediatric
      brain tumour survivors: work and finances, daily and social functioning, and
      legal difficulties.
AB  - BACKGROUND: Paediatric brain tumour survivors (PBTS) are at high risk for
      medical, neurocognitive and psychological sequelea during adulthood. Details
      illustrating the types and breadth of these chronic sequelae are essential to
      fully comprehend their impact on daily living. PURPOSE: This study describes
      Canadian parents of PBTS perspectives of life challenges experienced by their now
      adult son or daughter related to work and finances, daily and social functioning,
      and legal difficulties. METHOD: Parents of PBTS completed an anonymous online
      exploratory survey. FINDINGS: Forty-six of 60 invited parents completed the
      survey. Parents reported that PBTS experienced difficulty gaining or sustaining
      employment (65 %) because of their health and/or a disability and employers
      reticence to hire and adequately support PBTS. Independent living was considered
      unaffordable for PBTS who received a disability allowance (82 %) and those who
      were employed (50 %). Thirty percent indicated their family experienced hardship
      because of PBTS medical expenses, which were usually paid for out of pocket (76
      %). Although the majority of PBTS were independent with daily tasks and social
      functioning, a subgroup required continuous support. Forty percent of employed
      PBTS received limited assistance to accommodate their special needs. Parents
      indicated their son or daughter had been the victim of theft, fraud or assault
      (37 %), and commonly considered them vulnerable, in need of protection and feared
      for their future safety. CONCLUSION: Research that further illuminates the
      hardships facing PBTS and informs the development of support and resources to
      address PBTS vulnerabilities is warranted. IMPLICATIONS FOR CANCER SURVIVORS:
      PBTS are at risk for unemployment, financial challenges and legal difficulties,
      which appear to be poorly addressed by health and social programs.

PMID- 24563169
TI  - Quality of cancer follow-up care: a focus on Latina breast cancer survivors.
AB  - INTRODUCTION: Receiving quality cancer follow-up care influences survivorship
      outcomes. Among Latinas, breast cancer is the number one cause of cancer death;
      yet Latinas do not receive adequate follow-up care. This study examined quality
      of cancer follow-up care among Latina breast cancer survivors (BCS) and whether
      it differs by participant language and healthcare system variables (provider
      specialty, and medical setting). METHODS: Two hundred thirty-two (95 English
      speaking Latina and 137 Spanish-speaking) Latina BCS were recruited from the
      California Cancer Registry, hospital cancer registries, and community agencies.
      RESULTS: English-speaking Latina BCS were more likely to report receiving cancer
      follow-up care at a doctor's office (p < 0.001). BCS without a regular place for
      cancer follow-up care were more likely to report not seeing a primary care
      provider (p < 0.05) or cancer specialist (p < 0.001) in the past 12 months.
      English-speaking Latina BCS (p < 0.001), BCS who saw a cancer specialist in the
      past 12 months (p < 0.001), and received follow-up care at a doctor's office (p <
      0.05) reported higher quality of care. Speaking English, having seen a cancer
      specialist, and receiving follow-up care at a doctor's office were independently
      associated with higher quality of care, explaining 44 % of the variance.
      CONCLUSIONS: Our study findings suggest that examining the influence of ethnic
      and linguistic factors on quality of cancer follow-up care is necessary to
      address health disparities. Improved access to cancer follow-up care for Spanish
      speaking Latina BCS is of particular concern. IMPLICATION OF CANCER SURVIVORS:
      Identifying follow-up care needs of Latina BCS may contribute to providing high
      quality care and improved survivorship outcomes.

PMID- 24563170
TI  - Risk factors in the mother-child relationship that predispose to the development
      of early childhood caries.
AB  - AIM: This study focused on the risk factors in mother-child relationship that
      predispose babies to the development of dental caries. METHODS: A prospective
      cohort study with 80 mother-child pairs was conducted. The mothers responded at
      12, 18 and 30 months after their children's birth, to questions about variables
      related to diet, sucking habits, and oral care. Children were clinically examined
      to verify caries lesions (white spot lesions or cavitation). Data were analysed
      using Chi squared or Fisher's exact tests. The significance level was set at 5%.
      RESULTS: Of the total, 3.75% showed cavitated lesions after 18 months; 6.25 and
      45% had spot white lesions, respectively, at 18 and 30 months. The cariogenic
      diet was high at 12 (63.75%) and 30 (88.75%) months. Good oral hygiene was
      present in a minority of children at 12 months (46.25%), but increased at 30
      months (65%), helping to prevent cavities and white spot lesions over this period
      (p = 0.0005). The variables of the blocks sucking habits and diet were not
      associated with caries. CONCLUSION: The lack of oral care in children was a risk
      factor for dental caries development.

PMID- 24563171
TI  - Presentation and management of facial swellings of odontogenic origin in
      children.
AB  - AIM: To determine the characteristics, aetiology and management of facial
      swellings of odontogenic origin in the paediatric population. STUDY DESIGN:
      Prospective study of children with facial swellings of odontogenic origin.
      METHODS: All children who presented to the Departments of Paediatric Dentistry of
      the Westmead Centre for Oral Health and the Children's Hospital at Westmead with
      a facial swelling of odontogenic origin over a 12 month period were identified
      and included in the study. Treating clinicians completed a standardised data
      collection sheet to record information relating to patient demographics, medical
      history, dental history, history of current episode of facial swelling of
      odontogenic origin, examination findings and management. Data were entered in
      Microsoft((r)) Excel and statistical analysis carried out using Statistical
      Analysis Software((r)) version 9.3. RESULTS/STATISTICS: Two hundred and fifty
      three children were included in the study, with a mean age of 6.3 years. Sixteen
      percent of children were admitted for intravenous antibiotics, surgical
      management and supportive care. For the remaining children not admitted, a range
      of management approaches were undertaken. These included immediate surgical
      management with or without oral antibiotics, delayed surgical management
      following a course of oral antibiotics, or oral antibiotics alone, where the
      cause of the odontogenic infection had already been removed. For 2% of children,
      a delayed surgical management approach was unsuccessful and the children were
      admitted. CONCLUSIONS: Management options for children presenting with facial
      swellings of odontogenic origin include admission to hospital for intravenous
      antibiotics and acute surgical management, immediate surgical management with or
      without a course of oral antibiotics or initial management involving a course of
      oral antibiotics, with definitive dental treatment being provided after
      resolution of the acute odontogenic infection.

PMID- 24563172
TI  - Occlusion and occlusal characteristics of primary dentition in North Indian
      children of East Lucknow region.
AB  - AIM: To determine occlusion and occlusal characteristics of the primary dentition
      in North Indian school-going children of East Lucknow region. STUDY DESIGN: A
      cross-sectional study was conducted on 453 participants in the age group of 3-6
      years. METHODS: Participants were selected randomly and occlusal relationship was
      assessed based on Baume's classification. Various other occlusal characteristics
      were also recorded and assessed based on clinical and photographic evaluation.
      The data were then subjected to statistical analysis. RESULTS: Out of 453
      participants examined, results revealed 62.3% had flush terminal plane; 31.3%
      mesial step molar relationship and 6.4% distal step molar relationship. It was
      also observed that 91.6% had Class I canine relationship, 93.4% primate spaces,
      69.5% physiologic spaces. Amongst other occlusal characteristics, increased
      overbite and crowding were prevalent. Association of various occlusal
      characteristics and oral habits with respect to primary molar relation was also
      assessed. STATISTICS: Chi-square test was performed to carry out statistical
      analysis. p value <0.05 was taken as statistically significant. CONCLUSION: It
      was found that flush terminal plane relationship with spacing and Class I canine
      relationship predominated. Further prospective studies are required to provide an
      insight into patterns of occlusal relationship and its changes in Indian
      children.

PMID- 24563173
TI  - Root canal morphology of primary molars: a micro-computed tomography study.
AB  - AIM: This was to investigate the root canal morphology of primary molar teeth
      using micro-computed tomography. METHODS: Primary maxillary (n = 20) and
      mandibular (n = 20) molars were scanned at a resolution of 16.7 MUm and analysed
      regarding the number, location, volume, area, structured model index (SMI), area,
      roundness, diameters, and length of canals, as well as the thickness of dentine
      in the apical third. Data were statistically compared by using paired-sample t
      test, independent sample t test, and one-way analysis of variance with
      significance level set as 5%. RESULTS: Overall, no statistical differences were
      found between the canals with respect to length, SMI, dentine thickness, area,
      roundness, and diameter (p > 0.05). A double canal system was observed in the
      mesial and mesio-buccal roots of the mandibular and maxillary molars,
      respectively. The thickness in the internal aspect of the roots was lower than in
      the external aspect. Cross-sectional evaluation of the roots in the apical third
      showed flat-shaped canals in the mandibular molars and ribbon- and oval-shaped
      canals in the maxillary molars. CONCLUSIONS: External and internal anatomy of the
      primary first molars closely resemble the primary second molars. The reported
      data may help clinicians to obtain a thorough understanding of the morphological
      variations of root canals in primary molars to overcome problems related to
      shaping and cleaning procedures, allowing appropriate management strategies for
      root canal treatment.

PMID- 24563174
TI  - Mechanisms of pharmaceutical aerosol deposition in the respiratory tract.
AB  - Aerosol delivery is noninvasive and is effective in much lower doses than
      required for oral administration. Currently, there are several types of
      therapeutic aerosol delivery systems, including the pressurized metered-dose
      inhaler, the dry powder inhaler, the medical nebulizer, the solution mist
      inhaler, and the nasal sprays. Both oral and nasal inhalation routes are used for
      the delivery of therapeutic aerosols. Following inhalation therapy, only a
      fraction of the dose reaches the expected target area. Knowledge of the amount of
      drug actually deposited is essential in designing the delivery system or devices
      to optimize the delivery efficiency to the targeted region of the respiratory
      tract. Aerosol deposition mechanisms in the human respiratory tract have been
      well studied. Prediction of pharmaceutical aerosol deposition using established
      lung deposition models has limited success primarily because they underestimated
      oropharyngeal deposition. Recent studies of oropharyngeal deposition of several
      drug delivery systems identify other factors associated with the delivery system
      that dominates the transport and deposition of the oropharyngeal region.
      Computational fluid dynamic simulation of the aerosol transport and deposition in
      the respiratory tract has provided important insight into these processes.
      Investigation of nasal spray deposition mechanisms is also discussed.

PMID- 24563175
TI  - A systematic approach to design and prepare solid dispersions of poorly water
      soluble drug.
AB  - The objective of the present study was to define a systematic approach to design
      and prepare solid dispersions of poorly water-soluble drug. The systematic
      approach can be defined in four phases. In the first phase, glass forming ability
      is assessed, and in the second phase, probable excipients are screened. The
      screened excipients are evaluated (third phase) for glass transition temperatures
      (Tg) and miscibility studies according to Florey-Huggins interaction parameter.
      The predicted excipients are used to prepare the solid dispersion and evaluated
      for Tg and any interactions using Fourier transfer infrared studies (fourth
      phase), and the findings are correlated with phase three predictions. For this
      investigation, cilostazol (CIL) was selected as model drug, which was classified
      as a poor glass former. As per the physical chemical properties of CIL, ten
      excipients, both polymeric and non-polymeric, were selected and screened. Out of
      these, povidone, copovidone, hypromellose and Eudragit EPO were found
      theoretically miscible with CIL. After going through phase 2 to phase 4, only
      povidone, copovidone and hypromellose were confirmed as polymer of choice for
      preparing the solid dispersion of CIL with a prediction of better physical solid
      state stability on the basis of good miscibility between drug and carrier.

PMID- 24563176
TI  - Platelet factor 4/heparin-particle gel immunoassay (PaGIA) is a weak method for
      heparin-induced thrombocytopenia (HIT) evaluation of post cardio-pulmonary bypass
      surgery patients.
AB  - Diagnosis of heparin induced thrombocytopenia (HIT) is not always easy,
      especially when a confirmatory functional test is not available. In most cases
      the diagnosis relies on the combination of pretest probability and an immunologic
      test. Among patients post cardiopulmonary bypass (CPB) surgery, anti-platelet
      factor 4/heparin antibodies tend to be high but with low clinical implication.
      The current retrospective study examined the behavior of patients with positive
      PF4/heparin-PaGIA results, divided into two groups according to whether or not
      they have undergone CPB surgery. The main focus of the study was on the
      reliability of the PF4/heparin-PaGIA test in these two settings. The files of 104
      single center patients, who had a positive PF4/heparin-PaGIA test, were reviewed.
      62% were post CPB and 38% were not. An association between the intensity of
      positivity of PF4/heparin-PaGIA test and both the 4Ts pretest probability method
      (p = 0.003) and the incidence of thrombosis (p = 0.02) was found only in the
      patients who have not undergone CPB surgery, but not in the CPB patients. This
      study suggests that PF4/heparin-PaGIA is not a reliable method in patients post
      CPB surgery who are investigated for a possible diagnosis of HIT.

PMID- 24563177
TI  - "Don't know" and accuracy of breast cancer risk perceptions among Appalachian
      women attending a mobile mammography program: implications for educational
      interventions and patient empowerment.
AB  - Risk perceptions are motivating factors for engaging in preventive health
      behaviors. Yet, almost one third of women attending a mobile mammography program
      targeted to rural and medically underserved Appalachian women respond "don't
      know" to their perceived 5-year risk of breast cancer. This study used cross
      sectional data from women aged >40 years participating in Bonnie's Bus
      Mammography Screening and Preventive Care Survey from 2009 to 2011 to identify
      factors associated with "don't know" responses and accuracy of perceived risk
      according to constructs of the health belief model and sociodemographic
      characteristics. Women who responded "don't know" were more likely to be less
      educated, of lower income, insured by Medicaid, and less knowledgeable about
      breast cancer. Conversely, women who accurately perceived their risk were more
      likely to be of higher education, more knowledgeable about breast cancer, and
      have a family history of breast cancer. However, women with a high objective 5
      year risk of breast cancer and older age at childbirth or were nulliparous were
      less likely to accurately perceive their risk. These findings suggest that women
      who indicate "don't know" responses and hold inaccurate risk perceptions are a
      population vulnerable to health disparities and may benefit from educational
      interventions focused on improving breast cancer knowledge and perceptions to
      empower them to take an active role in their preventive health and make informed
      decisions based on their individual level of risk.

PMID- 24563178
TI  - Evaluation of chest compression effect on airway management with air-Q, aura-i, i
      gel, and Fastrack intubating supraglottic devices by novice physicians: a
      randomized crossover simulation study.
AB  - PURPOSE: In the 2010 American Heart Association guidelines, supraglottic devices
      (SGDs) such as the laryngeal mask are proposed as alternatives to tracheal
      intubation for cardiopulmonary resuscitation. Some SGDs can also serve as a means
      for tracheal intubation after successful ventilation. The purpose of this study
      was to evaluate the effect of chest compression on airway management with four
      intubating SGDs, aura-i (aura-i), air-Q (air-Q), i-gel (i-gel), and Fastrack
      (Fastrack), during cardiopulmonary resuscitation using a manikin. METHODS: Twenty
      novice physicians inserted the four intubating SGDs into a manikin with or
      without chest compression. Insertion time and successful ventilation rate were
      measured. For cases of successful ventilation, blind tracheal intubation via the
      intubating SGD was performed with chest compression and success or failure within
      30 s was recorded. RESULTS: Chest compression did not decrease the ventilation
      success rate of the four intubating SGDs (without chest compression
      (success/total): air-Q, 19/20; aura-i, 19/20; i-gel, 18/20; Fastrack, 19/20; with
      chest compression: air-Q, 19/20; aura-i, 19/20; i-gel, 16/20; Fastrack, 18/20).
      Insertion time was significantly lengthened by chest compression in the i-gel
      trial (P < 0.05), but not with the other three devices. The blind intubation
      success rate with chest compression was the highest in the air-Q trial (air-Q,
      15/19; aura-i, 14/19; i-gel, 12/16; Fastrack, 10/18). CONCLUSIONS: This
      simulation study revealed the utility of intubating SGDs for airway management
      during chest compression.

PMID- 24563179
TI  - Whole-body MRI for initial staging of paediatric lymphoma: prospective comparison
      to an FDG-PET/CT-based reference standard.
AB  - OBJECTIVE: To compare whole-body MRI, including diffusion-weighted imaging (whole
      body MRI-DWI), with FDG-PET/CT for staging newly diagnosed paediatric lymphoma.
      METHODS: A total of 36 children with newly diagnosed lymphoma prospectively
      underwent both whole-body MRI-DWI and FDG-PET/CT. Whole-body MRI-DWI was
      successfully performed in 33 patients (mean age 13.9 years). Whole-body MRI-DWI
      was independently evaluated by two blinded observers. After consensus reading, an
      unblinded expert panel evaluated the discrepant findings between whole-body MRI
      DWI and FDG-PET/CT and used bone marrow biopsy, other imaging data and clinical
      information to derive an FDG-PET/CT-based reference standard. RESULTS:
      Interobserver agreement of whole-body MRI-DWI was good [all nodal sites together
      (kappa = 0.79); all extranodal sites together (kappa = 0.69)]. There was very
      good agreement between the consensus whole-body MRI-DWI- and FDG-PET/CT-based
      reference standard for nodal (kappa = 0.91) and extranodal (kappa = 0.94)
      staging. The sensitivity and specificity of consensus whole-body MRI-DWI were 93
      % and 98 % for nodal staging and 89 % and 100 % for extranodal staging,
      respectively. Following removal of MRI reader errors, the disease stage according
      to whole-body MRI-DWI agreed with the reference standard in 28 of 33 patients.
      CONCLUSIONS: Our results indicate that whole-body MRI-DWI is feasible for staging
      paediatric lymphoma and could potentially serve as a good radiation-free
      alternative to FDG-PET/CT. KEYPOINTS: * Accurate staging is important for
      treatment planning and assessing prognosis * Whole-body MRI-DWI could be a good
      radiation-free alternative to FDG-PET/CT * Interobserver agreement of whole-body
      MRI-DWI is good * Agreement between whole-body MRI and the FDG-PET/CT reference
      standard is good * Most discrepancies were caused by suboptimal accuracy of size
      measurements on MRI.

PMID- 24563180
TI  - Aromatase inhibitors for subfertile women with polycystic ovary syndrome.
AB  - BACKGROUND: Polycystic ovary syndrome (PCOS) is the most common cause of
      infrequent periods (oligomenorrhoea) and absence of periods (amenorrhoea). It
      affects about 4% to 8% of women worldwide and often leads to anovulatory
      subfertility. Aromatase inhibitors (AIs) are a novel class of drugs that were
      introduced for ovulation induction in 2001. Over the last ten years clinical
      trials have reached differing conclusions as to whether the AI letrozole is at
      least as effective as the first-line treatment clomiphene citrate (CC).
      OBJECTIVES: To evaluate the effectiveness and safety of aromatase inhibitors for
      subfertile women with anovulatory PCOS. SEARCH METHODS: We searched the following
      sources from inception to 24/10/2013 to identify relevant randomised controlled
      trials (RCTs): the Menstrual Disorders and Subfertility Group Specialised
      Register, the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE,
      PsycINFO, Pubmed, LILACS, Web of Knowledge, the World Health Organisation (WHO)
      clinical trials register and Clinicaltrials.gov. Furthermore, we manually
      searched the references of relevant articles.The search was not restricted by
      language or publication status. SELECTION CRITERIA: We included all RCTs of
      aromatase inhibitors used alone or with other medical therapies for ovulation
      induction in women of reproductive age with anovulatory PCOS. DATA COLLECTION AND
      ANALYSIS: Two review authors independently selected trials, extracted the data
      and assessed trial quality. Studies were pooled where appropriate using a fixed
      effect model to calculate pooled odds ratios (ORs) and 95% confidence intervals
      (CIs) for most outcomes and risk differences (RDs) for ovarian hyperstimulation
      syndrome (OHSS). The primary outcomes were live birth and OHSS. Secondary
      outcomes were pregnancy, miscarriage and multiple pregnancy. The quality of the
      evidence for each comparison was assessed using GRADE methods. MAIN RESULTS: We
      included 26 RCTs (5560 women). In all studies the aromatase inhibitor was
      letrozole. Live birth (12 RCTs) One RCT compared letrozole with placebo in women
      who were clomiphene resistant and the results were inconclusive (OR 3.17, 95% CI
      0.12 to 83.17, n=36)Nine RCTs compared letrozole with clomiphene citrate (with or
      without adjuncts) followed by timed intercourse. The birth rate was higher in the
      letrozole group (OR 1.63, 95% CI 1.31 to 2.03, n=1783, I2=3%)Two RCTs compared
      letrozole with laparoscopic ovarian drilling. There was no evidence of a
      difference between the groups in live birth rate (OR 1.19, 95% CI 0.76 to 1.86,
      n=407, I2=0%) OHSS (16 RCTs) There was no evidence of a difference in OHSS rates
      when letrozole was compared with placebo (one RCT, n=36), clomiphene citrate
      (with or without adjuncts) followed by timed intercourse (nine RCTs, n=2179),
      clomiphene citrate (with or without adjuncts) followed by intrauterine
      insemination (IUI) (two RCTs, n=1494), laparoscopic ovarian drilling (one RCT,
      n=260) or anastrozole (one RCT, n=220). Events were absent or very rare, and no
      study had more than 2 cases of OHSS. Clinical pregnancy (25 RCTs) One RCT
      compared letrozole versus placebo in women who were clomiphene resistant and the
      results were inconclusive (OR 3.17, 95% CI 0.12 to 83.17, n=36)Fourteen RCTs
      compared letrozole versus clomiphene citrate (with or without adjuncts) followed
      by timed intercourse. The pregnancy rate was higher in the letrozole group (OR
      1.32, 95% CI 1.09 to 1.60, n=2066, I2=25%)Three RCTs compared letrozole versus
      clomiphene citrate (with or without adjuncts) followed by IUI. The pregnancy rate
      was higher in the letrozole group (OR 1.71, 95% CI 1.30 to 2.25, n=1597)Three
      RCTs compared letrozole versus laparoscopic ovarian drilling. There was no
      evidence of a difference in the clinical pregnancy rate (OR 1.14, 95% CI 0.80 to
      1.65, n=553, I2=0%)Two RCTs compared letrozole versus anastrozole, one RCT
      compared a five day versus a 10 day administration protocol for letrozole and
      another RCT compared 5 mg of letrozole versus 7.5 mg of letrozole. There was no
      evidence of a difference in the clinical pregnancy rate in these comparisons.The
      quality of the evidence was rated as low for live birth and pregnancy outcomes.
      The reasons for downgrading the evidence were poor reporting of study methods,
      possible publication bias and the tendency for studies that reported live birth
      to report higher clinical pregnancy rates in the letrozole group than studies
      that failed to report live birth (suggesting that results might be somewhat less
      favourable to letrozole if all studies reported live birth). AUTHORS'
      CONCLUSIONS: Letrozole appears to improve live birth and pregnancy rates in
      subfertile women with anovulatory PCOS, compared to clomiphene citrate. The
      quality of this evidence is low and findings should be regarded with some
      caution. There appears to be no difference in effectiveness between letrozole and
      laparoscopic ovarian drilling, though there were few relevant studies. OHSS was a
      very rare event, with no occurrences in most studies.

PMID- 24563182
TI  - Clitocine targets Mcl-1 to induce drug-resistant human cancer cell apoptosis in
      vitro and tumor growth inhibition in vivo.
AB  - Drug resistance is a major reason for therapy failure in cancer. Clitocine is a
      natural amino nucleoside isolated from mushroom and has been shown to inhibit
      cancer cell proliferation in vitro. In this study, we observed that clitocine can
      effectively induce drug-resistant human cancer cell apoptosis in vitro and
      inhibit tumor xenograft growth in vivo. Clitocine treatment inhibited drug
      resistant human cancer cell growth in vitro in a dose- and time-dependent manner.
      Biochemical analysis revealed that clitocine-induced tumor growth inhibition is
      associated with activation of caspases 3, 8 and 9, PARP cleavage, cytochrome c
      release and Bax, Bak activation, suggesting that clitocine inhibits drug
      resistant cancer cell growth through induction of apoptosis. Analysis of
      apoptosis regulatory genes indicated that Mcl-1 level was dramatically decreased
      after clitocine treatment. Over-expression of Mcl-1 reversed the activation of
      Bax and attenuated clitocine-induced apoptosis, suggesting that clitocine-induced
      apoptosis was at least partially by inducing Mcl-1 degradation to release Bax and
      Bak. Consistent with induction of apoptosis in vitro, clitocine significantly
      suppressed the drug-resistant hepatocellular carcinoma xenograft growth in vivo
      by inducing apoptosis as well as inhibiting cell proliferation. Taken together,
      our data demonstrated that clitocine is a potent Mcl-1 inhibitor that can
      effectively induce apoptosis to suppress drug-resistant human cancer cell growth
      both in vitro and in vivo, and thus holds great promise for further development
      as potentially a novel therapeutic agent to overcome drug resistance in cancer
      therapy.

PMID- 24563184
TI  - Effects of alcohol hangover on simulated highway driving performance.
AB  - BACKGROUND: The purpose of this study was to examine the effects of alcohol
      hangover on simulated highway driving performance. METHODS: Driving performance
      of forty-two social drinkers was tested the morning following an evening of
      consuming on average 10.2 (SD = 4.2) alcoholic drinks (alcohol hangover) and on a
      control day (no alcohol consumed). Subjects performed a standardized 100-km
      highway driving test in the STISIM driving simulator. In addition to the standard
      deviation of lateral position (SDLP; i.e., the weaving of the car), lapses of
      attention were examined. Self-reported driving quality and driving style were
      scored, as well as mental effort to perform the test, sleepiness before and after
      driving, and hangover severity. RESULTS: Driving performance was significantly
      impaired during alcohol hangover as expressed by an SDLP increase of +1.9 cm (t
      (1,41) = 2.851, p = 0.007), increased number of lapses relative to the control
      day (7.7 versus 5.3 lapses, t (1,41) = 2.125, p = 0.019), and an increased total
      lapse time (182.7 versus 127.3 s, p = 0.040). During alcohol hangover, subjects
      reported their driving quality to be significantly poorer (t (1,41) = 4.840, p =
      0.001) and less safe (t (1,41) = 5.078, p = 0.001), wise (t (1,41) = 4.061, p =
      0.001), predictable (t (1,41) = 3.475, p = 0.001), and responsible (t (1,41) =
      4.122, p = 0.001). Subjects further reported being significantly more tense while
      driving (t (1,41) = 3.280, p = 0.002), and more effort was needed to perform the
      driving test (t (1,41) = 2.941, p = 0.001). There was a significant interaction
      with total sleep time and hangover effects on SDLP and the number of lapses.
      CONCLUSIONS: In conclusion, driving is significantly impaired during alcohol
      hangover, as expressed in an elevated SDLP and increased number of lapses. Total
      sleep time has a significant impact on the magnitude of driving impairment.

PMID- 24563186
TI  - Effect of age on methylphenidate-induced conditioned taste avoidance and related
      BDNF/TrkB signaling in the insular cortex of the rat.
AB  - RATIONALE: Drug use and abuse is thought to be a function of the balance between
      its rewarding and aversive effects, such that the rewarding effects increase the
      likelihood of use while the drug's dissociable aversive effects limit it.
      Adolescents exhibit a shift in this balance toward reward, which may ultimately
      lead to increased use. Importantly, recent work shows that adolescents are also
      protected from the aversive effects of many abusable drugs as measured by
      conditioned taste avoidance (CTA). However, such effects of methylphenidate (MPH,
      widely prescribed to adolescents with ADHD) have not been characterized.
      OBJECTIVES: The effect of age on MPH-induced CTA was assessed. In addition, MPH
      induced changes in brain-derived neurotrophic factor (BDNF) activity in the
      insular cortex (IC) and central nucleus of the amygdala (CeA), known to be
      important to CTA, were examined and related to CTAs in adolescents and adults.
      METHODS: CTAs induced by MPH (0, 10, 18, and 32 mg/kg) were assessed in
      adolescent (n = 34) and adult (n = 33) male Sprague Dawley rats. Following MPH
      CTA, IC and CeA tissue was probed for differences in BDNF and tropomyosin-related
      kinase receptor-B (TrkB) using Western blots. RESULTS: Blunted expression of MPH
      CTA was observed in the adolescents versus adults, which correlated with
      generally attenuated adolescent BDNF/TrkB activity in the IC, but the drug
      effects ran contrary to the expression of CTA. CONCLUSIONS: Adolescents are
      protected from the aversive effects of MPH versus adults, but further work is
      needed to characterize the possible involvement of BDNF/TrkB.

PMID- 24563185
TI  - Mice deficient in phosphodiesterase-4A display anxiogenic-like behavior.
AB  - RATIONALE: Phosphodiesterases (PDEs) are a super family of enzymes responsible
      for the halting of intracellular cyclic nucleotide signaling and may represent
      novel therapeutic targets for treatment of cognitive disorders. PDE4 is of
      considerable interest to cognitive research because it is highly expressed in the
      brain, particularly in the cognition-related brain regions. Recently, the
      functional role of PDE4B and PDE4D, two of the four PDE4 subtypes (PDE4A, B, C,
      and D), in behavior has begun to be identified; however, the role of PDE4A in the
      regulation of behavior is still unknown. OBJECTIVES: The purpose of this study
      was to characterize the functional role of PDE4A in behavior. METHODS: The role
      of PDE4A in behavior was evaluated through a battery of behavioral tests using
      PDE4A knockout (KO) mice; urine corticosterone levels were also measured.
      RESULTS: PDE4A KO mice exhibited improved memory in the step-through-passive
      avoidance test. They also displayed anxiogenic-like behavior in elevated-plus
      maze, holeboard, light-dark transition, and novelty suppressed feeding tests.
      Consistent with the anxiety profile, PDE4A KO mice had elevated corticosterone
      levels compared with wild-type controls post-stress. Interestingly, PDE4A KO mice
      displayed no change in object recognition, Morris water maze, forced swim, tail
      suspension, and duration of anesthesia induced by co-administration of xylazine
      and ketamine (suggesting that PDE4A KO may not be emetic). CONCLUSIONS: These
      results suggest that PDE4A may be important in the regulation of emotional memory
      and anxiety-like behavior, but not emesis. PDE4A could possibly represent a novel
      therapeutic target in the future for anxiety or disorders affecting memory.

PMID- 24563187
TI  - Fulminant puerperal sepsis due to anaplastic large-cell lymphoma (ALCL) with
      therapy-refractory cerebral edema.
AB  - INTRODUCTION: Lymphoma is among the five most frequent malignancies during
      pregnancy while anaplastic large-cell lymphoma (ALCL) is rare, accounting only
      for 2-3 % of all adult-onset non-Hodgkin lymphomas. CASE REPORT: A 23-year-old
      gravida 1, para 1 presented with puerperal mastitis and septicemia following
      secondary cesarean section. Mastitis had been present for a week prior to
      delivery. A CT scan for further diagnostics revealed numerous prominent lymph
      nodes. Cerebrospinal fluid testing, bone marrow and lymph node biopsy confirmed
      diagnosis of ALCL. Systemic and intrathecal chemotherapy was initiated,
      stabilizing the patient's clinical situation. 30 days postpartum (pp.), a
      cerebral edema was diagnosed responsible for cerebro-venous hypoperfusion.
      Immediate ventricle drainage and further therapeutic measures revealed no
      improvement. The patient died 33 days pp. CONCLUSION: Puerperal septicemia
      seemingly caused by mastitis still needs rapid further evaluation if the
      patient's clinical presentation quickly declines despite antibiotic therapy.
      Immediate initiation of chemotherapy after confirmation of ALCL is required to
      increase the therapeutic benefit due to the poor prognosis of ALCL.

PMID- 24563188
TI  - A comparative study of obstetric outcomes in electively or spontaneously reduced
      triplet pregnancies.
AB  - PURPOSE: This study aimed at evaluating the pregnancy outcomes of IVF triplets
      which are spontaneously or electively reduced to twins and to compare them with
      non-reduced triplets and twins. METHODS: Retrospective analysis of trichorionic
      triplets and dichorionic twins of IVF pregnancies. RESULTS: Preeclampsia rate was
      significantly higher in triplet group (p = 0.014). Premature contractions
      requiring tocolysis were seen more often in spontaneous reduction and triplet
      groups compared to elective reduction and twin groups (p < 0.001). Elective
      reduction and twin groups had significantly lower rate of infants weighing less
      than 1,500 g than those of triplets (p < 0.001). Highest rate for infants
      weighing over 2,500 g was found in primary twin group. Preterm delivery rates
      were significantly lower in both twin and elective reduction groups compared to
      triplet and spontaneous reduction groups (p < 0.001). Proportion of women giving
      birth at term was not different in elective reduction and twin groups, and they
      were significantly higher compared to spontaneous reduction group (p = 0.024).
      Perinatal mortality rates of both elective reduction and twin groups were
      significantly less than those in the triplet group (p = 0.045 and p < 0.001,
      respectively). CONCLUSIONS: Obstetric outcomes of triplets from IVF or ovulation
      induction cycles undergoing elective reduction are better than ongoing triplet
      and spontaneous reduction groups and are similar to that of dichorionic twins.

PMID- 24563183
TI  - The behavioral pharmacology of zolpidem: evidence for the functional significance
      of alpha1-containing GABA(A) receptors.
AB  - RATIONALE: Zolpidem is a positive allosteric modulator of gamma-aminobutyric acid
      (GABA) with preferential binding affinity and efficacy for alpha1-subunit
      containing GABA(A) receptors (alpha1-GABA(A)Rs). Over the last three decades, a
      variety of animal models and experimental procedures have been used in an attempt
      to relate the behavioral profile of zolpidem and classic benzodiazepines (BZs) to
      their interaction with alpha1-GABA(A)Rs. OBJECTIVES: This paper reviews the
      results of rodent and non-human primate studies that have evaluated the effects
      of zolpidem on motor behaviors, anxiety, memory, food and fluid intake, and
      electroencephalogram (EEG) sleep patterns. Also included are studies that
      examined zolpidem's discriminative, reinforcing, and anticonvulsant effects as
      well as behavioral signs of tolerance and withdrawal. RESULTS: The literature
      reviewed indicates that alpha1-GABA(A)Rs play a principle role in mediating the
      hypothermic, ataxic-like, locomotor- and memory-impairing effects of zolpidem and
      BZs. Evidence also suggests that alpha1-GABA(A)Rs play partial roles in the
      hypnotic, EEG sleep, anticonvulsant effects, and anxiolytic-like of zolpidem and
      diazepam. These studies also indicate that alpha1-GABA(A)Rs play a more prominent
      role in mediating the discriminative stimulus, reinforcing, hyperphagic, and
      withdrawal effects of zolpidem and BZs in primates than in rodents. CONCLUSIONS:
      The psychopharmacological data from both rodents and non-human primates suggest
      that zolpidem has a unique pharmacological profile when compared with classic
      BZs. The literature reviewed here provides an important framework for studying
      the role of different GABA(A)R subtypes in the behavioral effects of BZ-type
      drugs and helps guide the development of new pharmaceutical agents for disorders
      currently treated with BZ-type drugs.

PMID- 24563189
TI  - Role of pelvic exenteration in the management of locally advanced primary and
      recurrent rectal cancer.
AB  - AIM: A review of a single-centre experience of pelvic exenteration as a treatment
      modality for patients with locally advanced primary and recurrent rectal cancer.
      The perioperative outcomes, morbidity and long term oncological outcomes are
      reviewed. MATERIALS & METHODS: Patients undergoing pelvic exenterations for
      recurrent and locally advanced rectal cancer between 1 January 2006 and 1 August
      2012 were identified from a prospective database. All patients underwent pre
      operative staging investigations with computed tomography (CT) scan of chest,
      abdomen and pelvis and pelvic magnetic resonance imaging (MRI). Patients with
      locally advanced primary rectal cancer were counselled for pre-operative
      chemoradiation. Structures such as the urinary bladder and female reproductive
      organs were resected en bloc where indicated with the lesion. Urological or
      plastic reconstructions were employed where indicated. The primary outcome
      measured was overall survival and secondary outcomes measured were time to local
      recurrence (LR) and systemic recurrence. Disease-free survival was examined by
      the Kaplan-Meier Method (Fig. 1). RESULTS: Pelvic exenterations were performed in
      13 patients with a median age of 59 (range 26-81). The rate of major post
      operative complications was 8% (n = 1), where the patient had anastomotic
      leakage. There were no mortalities in the perioperative period. All patients were
      operated with curative intent and negative circumferential margins were shown in
      9 out of 13 patients (70%). The DFS was 19.4 and the OS was 22.5 months.
      CONCLUSION: An aggressive approach with en bloc resection of organs involved
      provides survival benefit to patients with locally advanced primary and recurrent
      rectal cancer with an acceptable morbidity profile.

PMID- 24563190
TI  - Primary small cell carcinoma of the liver: a case report with immunohistochemical
      studies.

PMID- 24563193
TI  - Will SUMMIT reach the peak in COPD?

PMID- 24563191
TI  - Niche differentiation of ammonia-oxidising archaea (AOA) and bacteria (AOB) in
      response to paper and pulp mill effluent.
AB  - Sediment organic loading has been shown to affect estuarine nitrification and
      denitrification, resulting in changes to sediment biogeochemistry and nutrient
      fluxes detrimental to estuarine health. This study examined the effects of
      organic loading on nutrient fluxes and microbial communities in sediments
      receiving effluent from a paper and pulp mill (PPM) by applying microcosm studies
      and molecular microbial ecology techniques. Three sites near the PPM outfall were
      compared to three control sites, one upstream and two downstream of the outfall.
      The control sites showed coupled nitrification-denitrification with minimal
      ammonia release from the sediment. In contrast, the impacted sites were
      characterised by nitrate uptake and substantial ammonia efflux from the
      sediments, consistent with a decoupling of nitrification and denitrification.
      Analysis of gene diversity demonstrated that the composition of nitrifier
      communities was not significantly different at the impacted sites compared to the
      control sites; however, analysis of gene abundance indicated that whilst there
      was no difference in total bacteria, total archaea or ammonia-oxidising archaea
      (AOA) abundance between the control and impacted sites, there was a significant
      reduction in ammonia-oxidising bacteria (AOB) at the impacted sites. The results
      of this study demonstrate an effect of organic loading on estuarine sediment
      biogeochemistry and highlight an apparent niche differentiation between AOA and
      AOB. 

PMID- 24563192
TI  - Diversity, molecular phylogeny, and bioactive potential of fungal endophytes
      associated with the Himalayan blue pine (Pinus wallichiana).
AB  - In this study, we investigated the diversity of fungal endophytes associated with
      Pinus wallichiana from the Western Himalayas, with emphasis on comparison of
      endophytic communities harbored by the stem and needle tissues of the host and
      their antimicrobial potential. A total number of 130 isolates, comprising of 38
      different genera, were recovered from 210 fragments of the plant. Among the
      isolated fungi, only a single isolate, Tritirachium oryzae, belonged to the
      Phylum Basidiomycota whereas the rest belonged to Ascomycota. Dothideomycetes was
      the dominant class with the highest isolation frequency of 49.2 %. The most
      frequent colonizers of the host were Alternaria spp., Pestalotiopsis spp.,
      Preussia spp., and Sclerostagonospora spp. The diversity and species richness
      were higher in needle tissues than in the stems. Antimicrobial activities were
      displayed by extracts from a total number of 22 endophytes against one or more
      pathogens. Endophytes designated as P1N13 (Coniothyrium carteri), P2N8 (Thielavia
      subthermophila), P4S6b (Truncatella betulae), P7N10 (Cochliobolus australiensis),
      and P8S4 (Tritirachium oryzae) were highly active against Candida albicans. Broad
      spectrum antimicrobial activities were obtained with the extracts of P8-S4
      (Tritirachium oryzae) and P5-N26 (Coniochaeta gigantospora) that were potentially
      active against the Gram-positive and Gram-negative bacteria as well as the fungal
      pathogen, Candida albicans. The most prominent antagonistic activity against
      fungal pathogens was shown by P8-S4 (Tritirachium oryzae), P5-N31a (Truncatella
      spadicea), and P5-N20 (Fusarium larvarum). Our findings indicate that Pinus
      wallichiana harbors a rich endophytic fungal community with potential
      antimicrobial activities. Further studies are needed to understand the ecology
      and evolutionary context of the associations between the Himalayan pine and its
      endophytes.

PMID- 24563195
TI  - Trainee concerns regarding the Specialty Certificate Examination: results of a
      British Thoracic Society national survey: MRCP (UK) response.

PMID- 24563194
TI  - Cluster analysis in the COPDGene study identifies subtypes of smokers with
      distinct patterns of airway disease and emphysema.
AB  - BACKGROUND: There is notable heterogeneity in the clinical presentation of
      patients with COPD. To characterise this heterogeneity, we sought to identify
      subgroups of smokers by applying cluster analysis to data from the COPDGene
      study. METHODS: We applied a clustering method, k-means, to data from 10 192
      smokers in the COPDGene study. After splitting the sample into a training and
      validation set, we evaluated three sets of input features across a range of k
      (user-specified number of clusters). Stable solutions were tested for association
      with four COPD-related measures and five genetic variants previously associated
      with COPD at genome-wide significance. The results were confirmed in the
      validation set. FINDINGS: We identified four clusters that can be characterised
      as (1) relatively resistant smokers (ie, no/mild obstruction and minimal
      emphysema despite heavy smoking), (2) mild upper zone emphysema-predominant, (3)
      airway disease-predominant and (4) severe emphysema. All clusters are strongly
      associated with COPD-related clinical characteristics, including exacerbations
      and dyspnoea (p<0.001). We found strong genetic associations between the mild
      upper zone emphysema group and rs1980057 near HHIP, and between the severe
      emphysema group and rs8034191 in the chromosome 15q region (p<0.001). All
      significant associations were replicated at p<0.05 in the validation sample
      (12/12 associations with clinical measures and 2/2 genetic associations).
      INTERPRETATION: Cluster analysis identifies four subgroups of smokers that show
      robust associations with clinical characteristics of COPD and known COPD
      associated genetic variants.

PMID- 24563196
TI  - Aripiprazole treatment in a case of amphetamine-induced delusional infestation.

PMID- 24563197
TI  - Cerebral amyloid angiopathy presenting with neuropsychiatric symptoms.

PMID- 24563198
TI  - ICD-11 and operationalism.

PMID- 24563200
TI  - Breaking "bad" proteins to modulate abscisic acid signaling.

PMID- 24563199
TI  - Photoperiodic control of carbon distribution during the floral transition in
      Arabidopsis.
AB  - Flowering is a crucial process that demands substantial resources. Carbon
      metabolism must be coordinated with development through a control mechanism that
      optimizes fitness for any physiological need and growth stage of the plant.
      However, how sugar allocation is controlled during the floral transition is
      unknown. Recently, the role of a CONSTANS (CO) ortholog (Cr-CO) in the control of
      the photoperiod response in the green alga Chlamydomonas reinhardtii and its
      influence on starch metabolism was demonstrated. In this work, we show that
      transitory starch accumulation and glycan composition during the floral
      transition in Arabidopsis thaliana are regulated by photoperiod. Employing a
      multidisciplinary approach, we demonstrate a role for CO in regulating the level
      and timing of expression of the GRANULE BOUND STARCH SYNTHASE (GBSS) gene.
      Furthermore, we provide a detailed characterization of a GBSS mutant involved in
      transitory starch synthesis and analyze its flowering time phenotype in relation
      to its altered capacity to synthesize amylose and to modify the plant free sugar
      content. Photoperiod modification of starch homeostasis by CO may be crucial for
      increasing the sugar mobilization demanded by the floral transition. This finding
      contributes to our understanding of the flowering process.

PMID- 24563201
TI  - AUTOPHAGY-RELATED11 plays a critical role in general autophagy- and senescence
      induced mitophagy in Arabidopsis.
AB  - Autophagy-mediated turnover removes damaged organelles and unwanted cytoplasmic
      constituents and thus plays critical roles in cellular housekeeping and nutrient
      recycling. This "self eating" is tightly regulated by the AUTOPHAGY-RELATED1/13
      (ATG1/13) kinase complex, which connects metabolic and environmental cues to the
      vacuolar delivery of autophagic vesicles. Here, we describe the Arabidopsis
      thaliana accessory proteins ATG11 and ATG101, which help link the ATG1/13 complex
      to autophagic membranes. ATG11 promotes vesicle delivery to the vacuole but is
      not essential for synthesizing the ATG12-ATG5 and ATG8-phosphatidylethanolamine
      adducts that are central to autophagic vesicle assembly. ATG11, ATG101, ATG1, and
      ATG13 colocalize with each other and with ATG8, with ATG1 tethered to ATG8 via a
      canonical ATG8-interacting motif. Also, the presence of ATG11 encourages
      starvation-induced phosphorylation of ATG1 and turnover of ATG1 and ATG13. Like
      other atg mutants, ATG11-deficient plants senesce prematurely and are
      hypersensitive to nitrogen and fixed-carbon limitations. Additionally, we
      discovered that the senescence-induced breakdown of mitochondria-resident
      proteins and mitochondrial vesicles occurs via an autophagic process requiring
      ATG11 and other ATG components. Together, our data indicate that ATG11 (and
      possibly ATG101) provides important scaffolds connecting the ATG1/13 complex to
      both general autophagy and selective mitophagy.

PMID- 24563202
TI  - The synaptonemal complex protein ZYP1 is required for imposition of meiotic
      crossovers in barley.
AB  - In many cereal crops, meiotic crossovers predominantly occur toward the ends of
      chromosomes and 30 to 50% of genes rarely recombine. This limits the exploitation
      of genetic variation by plant breeding. Previous reports demonstrate that chiasma
      frequency can be manipulated in plants by depletion of the synaptonemal complex
      protein ZIPPER1 (ZYP1) but conflict as to the direction of change, with fewer
      chiasmata reported in Arabidopsis thaliana and more crossovers reported for rice
      (Oryza sativa). Here, we use RNA interference (RNAi) to reduce the amount of ZYP1
      in barley (Hordeum vulgare) to only 2 to 17% of normal zygotene levels. In the
      ZYP1(RNAi) lines, fewer than half of the chromosome pairs formed bivalents at
      metaphase and many univalents were observed, leading to chromosome nondisjunction
      and semisterility. The number of chiasmata per cell was reduced from 14 in
      control plants to three to four in the ZYP1-depleted lines, although the
      localization of residual chiasmata was not affected. DNA double-strand break
      formation appeared normal, but the recombination pathway was defective at later
      stages. A meiotic time course revealed a 12-h delay in prophase I progression to
      the first labeled tetrads. Barley ZYP1 appears to function similarly to ZIP1/ZYP1
      in yeast and Arabidopsis, with an opposite effect on crossover number to ZEP1 in
      rice, another member of the Poaceae.

PMID- 24563203
TI  - ABD1 is an Arabidopsis DCAF substrate receptor for CUL4-DDB1-based E3 ligases
      that acts as a negative regulator of abscisic acid signaling.
AB  - Members of the DDB1-CUL4-associated factors (DCAFs) family directly bind to
      DAMAGED DNA BINDING PROTEIN1 (DDB1) and function as the substrate receptors in
      CULLIN4-based E3 (CUL4) ubiquitin ligases, which regulate the selective
      ubiquitination of proteins. Here, we describe a DCAF protein, ABD1 (for ABA
      hypersensitive DCAF1), that negatively regulates abscisic acid (ABA) signaling in
      Arabidopsis thaliana. ABD1 interacts with DDB1 in vitro and in vivo, indicating
      that it likely functions as a CUL4 E3 ligase substrate receptor. ABD1 expression
      is induced by ABA, and mutations in ABD1 result in ABA- and NaCl-hypersensitive
      phenotypes. Loss of ABD1 leads to hyperinduction of ABA-responsive genes and
      higher accumulation of the ABA-responsive transcription factor ABA INSENSITIVE5
      (ABI5), hypersensitivity to ABA during seed germination and seedling growth,
      enhanced stomatal closure, reduced water loss, and, ultimately, increased drought
      tolerance. ABD1 directly interacts with ABI5 in yeast two-hybrid assays and
      associates with ABI5 in vivo by coimmunoprecipitation, and the interaction was
      found in the nucleus by bimolecular fluorescence complementation. Furthermore,
      loss of ABD1 results in a retardation of ABI5 degradation by the 26S proteasome.
      Taken together, these data suggest that the DCAF-CUL4 E3 ubiquitin ligase
      assembled with ABD1 is a negative regulator of ABA responses by directly binding
      to and affecting the stability of ABI5 in the nucleus.

PMID- 24563204
TI  - Synthetic lethality in the tobacco plastid ribosome and its rescue at elevated
      growth temperatures.
AB  - Consistent with their origin from cyanobacteria, plastids (chloroplasts) perform
      protein biosynthesis on bacterial-type 70S ribosomes. The plastid genomes of seed
      plants contain a conserved set of ribosomal protein genes. Three of these have
      proven to be nonessential for translation and, thus, for cellular viability:
      rps15, rpl33, and rpl36. To help define the minimum ribosome, here, we examined
      whether more than one of these nonessential plastid ribosomal proteins can be
      removed from the 70S ribosome. To that end, we constructed all possible double
      knockouts for the S15, L33, and L36 ribosomal proteins by stable transformation
      of the tobacco (Nicotiana tabacum) plastid genome. We find that, although S15 and
      L33 function in different ribosomal particles (30S and 50S, respectively), their
      combined deletion from the plastid genome results in synthetic lethality under
      autotrophic conditions. Interestingly, the lethality can be overcome by growth
      under elevated temperatures due to an improved efficiency of plastid ribosome
      biogenesis. Our results reveal functional interactions between protein and RNA
      components of the 70S ribosome and uncover the interdependence of the biogenesis
      of the two ribosomal subunits. In addition, our findings suggest that defining a
      minimal set of plastid genes may prove more complex than generally believed.

PMID- 24563206
TI  - Freshly frozen E18 rat cortical cells can generate functional neural networks
      after standard cryopreservation and thawing procedures.
AB  - Primary dissociated brain tissue from rodents is widely used in a variety of
      different scientific methods to investigate cellular processes in vitro. Often,
      for this purpose cell cultures need to be generated just on time, requiring
      extensive animal lab infrastructure. We show here that cryopreservation and
      thawing of dissociated tissue from rat cerebral cortex at embryonic day 18 is
      feasible without affecting its ability to form functional neuronal networks in
      vitro. Vitality of fresh and re-thawed cortical cells was comparable, assessed by
      CellTiter-Blue-assay, CytoTox-ONE assay, immunocytochemical characterization and
      in vitro neuronal network activity recordings on microelectrode arrays. These
      findings suggest that planning and execution of experiments might be considerably
      facilitated by using cryo-preserved neurons instead of acutely dissociated neural
      cultures due to fewer logistical issues with regard to animal breeding and
      pregnancy timed preparations. 

PMID- 24563207
TI  - Psychometric properties of the Eating Attitude Test-26 for female Iranian
      students.
AB  - OBJECTIVE: The main purpose of the present study was to assess the factor
      structure, the convergent and divergent validity, and the reliability of the
      Eating Attitude Test (EAT-26) in a sample of female Iranian students. METHOD:
      After a rigorous translation and back-translation of the EAT-26, 561 female
      students from the Tonekabon branch of the Islamic Azad University completed the
      EAT-26, the Binge Eating Scale (BES), the Beck Depression Inventory-II (BDI-II)
      and the Beck Anxiety Inventory (BAI). Six weeks later, 74 of these students
      participated in a test-retest procedure. RESULTS: The exploratory factor analysis
      resulted in a five-factor solution that accounted for 50% of the total variance.
      The factors included "drive for thinness", "restrained eating", "perceived social
      pressure to eat", "oral control", and "bulimia". These factors demonstrated
      satisfactory concurrent validity, acceptable to high internal consistency (0.76
      0.92), and low test-retest reliability (0.26-0.64). The factors effectively
      identified the students who were currently on a diet, and those who had never
      participated in a weight reduction program. CONCLUSION: The results provide mixed
      support for the reliability and validity of the EAT-26 for a non-clinical Iranian
      population. However, its discriminant validity makes it a useful measure for
      screening purposes and identifying women at risk for developing disordered eating
      or eating disorders. Future research should replicate this study in both non
      clinical and clinical settings in Iran.

PMID- 24563205
TI  - Targeted degradation of abscisic acid receptors is mediated by the ubiquitin
      ligase substrate adaptor DDA1 in Arabidopsis.
AB  - CULLIN4-RING E3 ubiquitin ligases (CRL4s) regulate key developmental and stress
      responses in eukaryotes. Studies in both animals and plants have led to the
      identification of many CRL4 targets as well as specific regulatory mechanisms
      that modulate their function. The latter involve COP10-DET1-DDB1 (CDD)-related
      complexes, which have been proposed to facilitate target recognition by CRL4,
      although the molecular basis for this activity remains largely unknown. Here, we
      provide evidence that Arabidopsis thaliana DET1-, DDB1-ASSOCIATED1 (DDA1), as
      part of the CDD complex, provides substrate specificity for CRL4 by interacting
      with ubiquitination targets. Thus, we show that DDA1 binds to the abscisic acid
      (ABA) receptor PYL8, as well as PYL4 and PYL9, in vivo and facilitates its
      proteasomal degradation. Accordingly, we found that DDA1 negatively regulates ABA
      mediated developmental responses, including inhibition of seed germination,
      seedling establishment, and root growth. All other CDD components displayed a
      similar regulatory function, although they did not directly interact with PYL8.
      Interestingly, DDA1-mediated destabilization of PYL8 is counteracted by ABA,
      which protects PYL8 by limiting its polyubiquitination. Altogether, our data
      establish a function for DDA1 as a substrate receptor for CRL4-CDD complexes and
      uncover a mechanism for the desensitization of ABA signaling based on the
      regulation of ABA receptor stability.

PMID- 24563211
TI  - In situ seed baiting to isolate germination-enhancing fungi for an epiphytic
      orchid, Dendrobium aphyllum (Orchidaceae).
AB  - Orchid conservation efforts, using seeds and species-specific fungi that support
      seed germination, require the isolation, identification, and germination
      enhancement testing of symbiotic fungi. However, few studies have focused on
      developing such techniques for the epiphytes that constitute the majority of
      orchids. In this study, conducted in Xishuangbanna Tropical Botanical Garden,
      Yunnan, China, we used seeds of Dendrobium aphyllum, a locally endangered and
      medicinally valuable epiphytic orchid, to attract germination promoting fungi. Of
      the two fungi isolated from seed baiting, Tulasnella spp. and Trichoderma spp.,
      Tulasnella, enhanced seed germination by 13.6 %, protocorm formation by 85.7 %,
      and seedling development by 45.2 % (all P < 0.0001). Epulorhiza, another seed
      germination promoting fungi isolated from Cymbidium mannii, also enhanced seed
      germination (6.5 %; P < 0.05) and protocorm formation (20.3 %; P < 0.0001), but
      Trichoderma suppressed seed germination by 26.4 % (P < 0.0001). Tulasnella was
      the only treatment that produced seedlings. Light increased seed imbibition,
      protocorm formation, and two-leaved seed development of Tulasnella inoculated
      seeds (P < 0.0001). Because the germination stage success was not dependent on
      fungi, we recommend that Tulasnella be introduced for facilitating D. aphyllum
      seed germination at the protocorm formation stage and that light be provided for
      increasing germination as well as further seedling development. Our findings
      suggest that in situ seed baiting can be used to isolate seed germination
      enhancing fungi for the development of seedling production for conservation and
      reintroduction efforts of epiphytic orchids such as D. aphyllum. 

PMID- 24563212
TI  - Climatic variations explain annual fluctuations in French Perigord black truffle
      wholesale markets but do not explain the decrease in black truffle production
      over the last 48 years.
AB  - Production of the black truffle (Tuber melanosporum Vittad.) has experienced a
      decline in France over the last century. Different sociological factors as well
      as climate change have been suggested as possible explanations for this decline.
      The aims of this study were to assess the effects of annual climatic variations
      on black truffle sales by analysing reliable data. Over the past 25 years, almost
      90% of French truffle sales occurred in the southeastern region of France and,
      despite a decrease in southwestern France, for the last 25 years, sales were
      stable for France as a whole. An analysis of the two main southeastern wholesale
      markets (Richerenches and Carpentras) revealed that the main factor explaining
      the huge annual variations was the cumulative hydric balance from May to August
      of the year n. For the first time, frost days were also identified as an
      important factor in Richerenches. Using the model established for the past 25
      years and the climatic data for the Richerenches and Carpentras basins, the
      truffle sales would have been stable from 1965 to nowadays. This simulation
      suggested that the production decline observed since 48 years could be attributed
      more to the change of rural world than to the climatic changes. The stability of
      production or the slight increase observed during the last 25 years could reflect
      the input of truffle orchards recently planted.

PMID- 24563210
TI  - CUBN and NEBL common variants in the chromosome 10p13 linkage region are
      associated with multibacillary leprosy in Vietnam.
AB  - Leprosy is caused by infection with Mycobacterium leprae and is classified
      clinically into paucibacillary (PB) or multibacillary (MB) subtypes based on the
      number of skin lesions and the bacillary index detected in skin smears. We
      previously identified a major PB susceptibility locus on chromosome region 10p13
      in Vietnamese families by linkage analysis. In the current study, we conducted
      high-density association mapping of the 9.5 Mb linkage peak on chromosome region
      10p13 covering 39 genes. Using leprosy per se and leprosy subtypes as phenotypes,
      we employed 294 nuclear families (303 leprosy cases, 63 % MB, 37 % PB) as a
      discovery sample and 192 nuclear families (192 cases, 55 % MB, 45 % PB) as a
      replication sample. Replicated significant association signals were revealed in
      the genes for cubilin (CUBN) and nebulette (NEBL). In the combined sample, the C
      allele (frequency 0.26) at CUBN SNP rs10904831 showed association [p = 1 * 10(
      5); OR 0.52 (0.38-0.7)] with MB leprosy only. Likewise, allele T (frequency 0.42)
      at NEBL SNP rs11012461 showed association [p = 4.2 * 10(-5); OR 2.51 (1.6-4)]
      with MB leprosy only. These associations remained valid for the CUBN signal when
      taking into account the effective number of tests performed (type I error
      significance threshold = 2.4 * 10(-5)). We used the results of our analyses to
      propose a new model for the genetic control of polarization of clinical leprosy.

PMID- 24563214
TI  - Matricellular proteins: multifaceted extracellular regulators in tumor dormancy.

PMID- 24563215
TI  - The gain of hydrogen peroxide resistance benefits growth fitness in mycobacteria
      under stress.

PMID- 24563216
TI  - Accelerated regeneration of the skeletal muscle in RNF13-knockout mice is
      mediated by macrophage-secreted IL-4/IL-6.
AB  - RING finger protein 13 (RNF13) is a newly identified E3 ligase reported to be
      functionally significant in the regulation of cancer development, muscle cell
      growth, and neuronal development. In this study, the function of RNF13 in
      cardiotoxin-induced skeletal muscle regeneration was investigated using RNF13
      knockout mice. RNF13(-/-) mice exhibited enhanced muscle regeneration
      characterized by accelerated satellite cell proliferation-compared with wild-type
      mice. The expression of RNF13 was remarkably induced in macrophages rather than
      in the satellite cells of wild-type mice at the very early stage of muscle
      damage. This result indicated that inflammatory cells are important in RNF13
      mediated satellite cell functions. The cytokine levels in skeletal muscles were
      further analyzed and showed that RNF13(-/-) mice produced greater amounts of
      various cytokines than wild-type mice. Among these, IL-4 and IL-6 levels
      significantly increased in RNF13(-/-) mice. The accelerated muscle regeneration
      phenotype was abrogated by inhibiting IL-4/IL-6 action in RNF13(-/-) mice with
      blocking antibodies. These results indicate that RNF13 deficiency promotes
      skeletal muscle regeneration via the effects on satellite cell niche mediated by
      IL-4 and IL-6.

PMID- 24563218
TI  - Introduction of a manual vacuum aspiration service: a model of service within a
      NHS Sexual Health Service.
AB  - BACKGROUND: We assessed the applicability, acceptability and cost implications of
      introducing the manual vacuum aspiration (MVA) technique with local anaesthesia
      for fully conscious first-trimester termination of pregnancy within our service
      and for our population. SETTING: The outpatient setting of a Pregnancy Advisory
      Service within a NHS Sexual Health Service. METHODS: Self-administered
      misoprostol and diclofenac, extra-amniotic local anaesthetic gel and paracervical
      mepivicaine prior to MVA. Routinely collected data were used to provide
      information on uptake, demographic details, timing, pain score, complications,
      contraceptive uptake, and economic implications for our service. RESULTS: MVA was
      chosen by 305/1681 potentially eligible women. Forty percent had the procedure on
      the day they attended for assessment. Seventy-nine percent gave a pain score of 3
      or less out of 10. Complications occurred in six cases (2%); these included
      cervical rigidity, a false passage, retained products of conception, bleeding
      (more than 200 ml) and one allergic reaction. Eighty percent of women chose to
      commence a long-acting reversible contraception (LARC) method at the time of MVA.
      Operating theatre utilisation was reduced by one termination list per week and
      cost savings of around L60,000 per annum were realised. CONCLUSIONS: The
      technique for fully conscious MVA was very suitable for our outpatient setting.
      It was associated with very low levels of pain and bleeding. The uptake of LARC
      was high, and particularly the ability to provide intrauterine contraception at
      MVA was associated with a very high uptake.

PMID- 24563217
TI  - Telomere regulation in pluripotent stem cells.
AB  - Pluripotent stem cells (PSCs) have the potential to produce any types of cells
      from all three basic germ layers and the capacity to self-renew and proliferate
      indefinitely in vitro. The two main types of PSCs, embryonic stem cells (ESCs)
      and induced pluripotent stem cells (iPSCs), share common features such as colony
      morphology, high expression of Oct4 and Nanog, and strong alkaline phosphatase
      activity. In recent years, increasing evidences suggest that telomere length
      represents another important internal factor in maintaining stem cell
      pluripotency. Telomere length homeostasis and its structural integrity help to
      protect chromosome ends from recombination, end fusion, and DNA damage responses,
      ensuring the divisional ability of mammalian cells. PSCs generally exhibit high
      telomerase activity to maintain their extremely long and stable telomeres, and
      emerging data indicate the alternative lengthening of telomeres (ALT) pathway may
      play an important role in telomere functions too. Such characteristics are likely
      key to their abilities to differentiate into diverse cell types in vivo. In this
      review, we will focus on the function and regulation of telomeres in ESCs and
      iPSCs, thereby shedding light on the importance of telomere length to
      pluripotency and the mechanisms that regulate telomeres in PSCs. 

PMID- 24563219
TI  - T-type calcium channel blockers as neuroprotective agents.
AB  - T-type calcium channels are expressed in many diverse tissues, including
      neuronal, cardiovascular, and endocrine. T-type calcium channels are known to
      play roles in the development, maintenance, and repair of these tissues but have
      also been implicated in disease when not properly regulated. Calcium channel
      blockers have been developed to treat various diseases and their use clinically
      is widespread due to both their efficacy as well as their safety. Aside from
      their established clinical applications, recent studies have suggested
      neuroprotective effects of T-type calcium channel blockers. Many of the current T
      type calcium channel blockers could act on other molecular targets besides T-type
      calcium channels making it uncertain whether their neuroprotective effects are
      solely due to blocking of T-type calcium channels. In this review, we discuss
      these drugs as well as newly developed chemical compounds that are designed to be
      more selective for T-type calcium channels. We review in vitro and in vivo
      evidence of neuroprotective effects by these T-type calcium channel blockers. We
      conclude by discussing possible molecular mechanisms underlying the
      neuroprotective effects by T-type calcium channel blockers. 

PMID- 24563220
TI  - Cinnamaldehyde inhibits L-type calcium channels in mouse ventricular
      cardiomyocytes and vascular smooth muscle cells.
AB  - Cinnamaldehyde (CA), a major component of cinnamon, is known to have important
      actions in the cardiovascular system, including vasorelaxation and decrease in
      blood pressure. Although CA-induced activation of the chemosensory cation channel
      TRPA1 seems to be involved in these phenomena, it has been shown that genetic
      ablation of Trpa1 is insufficient to abolish CA effects. Here, we confirm that CA
      relaxes rat aortic rings and report that it has negative inotropic and
      chronotropic effects on isolated mouse hearts. Considering the major role of L
      type Ca(2+) channels in the control of the vascular tone and cardiac contraction,
      we used whole-cell patch-clamp to test whether CA affects L-type Ca(2+) currents
      in mouse ventricular cardiomyocytes (VCM, with Ca(2+) as charge carrier) and in
      mesenteric artery smooth muscle cells (VSMC, with Ba(2+) as charge carrier). We
      found that CA inhibited L-type currents in both cell types in a concentration
      dependent manner, with little voltage-dependent effects. However, CA was more
      potent in VCM than in VSMC and caused opposite effects on the rate of
      inactivation. We found these divergences to be at least in part due to the use of
      different charge carriers. We conclude that CA inhibits L-type Ca(2+) channels
      and that this effect may contribute to its vasorelaxing action. Importantly, our
      results demonstrate that TRPA1 is not a specific target of CA and indicate that
      the inhibition of voltage-gated Ca(2+) channels should be taken into account when
      using CA to probe the pathophysiological roles of TRPA1. 

PMID- 24563221
TI  - Amazing T-type calcium channels: updating functional properties in health and
      disease.
AB  - T-type Ca(2+) channels have gained, 15 years after cloning, an immense interest
      as novel players in very unexpected cell functions, and its many relations to
      diseases have been discovered. This special issue provides a state-of-the-art
      overview on novel functional properties of T-type Ca(2+) channels, unexpected
      cellular functions, and most importantly will also summarizes and review the
      involvement of this "tiny, transient" type of Ca(2+) channels in several
      diseases. It is tried to bridge the gap between molecular biophysical properties
      of T-type Ca(2+) channels and diseases providing finally a translational view on
      this amazing ion channel. 

PMID- 24563222
TI  - Voriconazole versus amphotericin B or fluconazole in cancer patients with
      neutropenia.
AB  - BACKGROUND: Opportunistic fungal infections are a major cause of morbidity and
      mortality in neutropenic cancer patients and antifungal therapy is used both
      empirically and therapeutically in these patients. OBJECTIVES: To compare the
      benefits and harms of voriconazole with those of amphotericin B and fluconazole
      when used for prevention or treatment of invasive fungal infections in cancer
      patients with neutropenia. SEARCH METHODS: Cochrane Central Register of
      Controlled Trials (CENTRAL) in The Cochrane Library (2014, Issue 1 2014), MEDLINE
      (to January 2014). Letters, abstracts and unpublished trials were accepted.
      Contact was made with trial authors and industry. SELECTION CRITERIA: Randomised
      clinical trials comparing voriconazole with amphotericin B or fluconazole. DATA
      COLLECTION AND ANALYSIS: Data on mortality, invasive fungal infection,
      colonisation, use of additional (escape) antifungal therapy and adverse effects
      leading to discontinuation of therapy were extracted independently by two review
      authors. MAIN RESULTS: Three trials were included. One trial compared
      voriconazole to liposomal amphotericin B as empirical treatment of fever of
      unknown origin (suspected fungal infection) in neutropenic cancer patients (849
      patients, 58 deaths). The second trial compared voriconazole to amphotericin B
      deoxycholate in the treatment of confirmed and presumed invasive Aspergillus
      infections (391 patients, 98 deaths). The third trial compared fluconazole to
      voriconazole for prophylaxis of fungal infections in patients receiving
      allogeneic stem cell transplantation (600 patients, number of deaths not stated).
      In the first trial, voriconazole was significantly inferior to liposomal
      amphotericin B according to the trial authors' prespecified criteria. More
      patients died in the voriconazole group and a claimed significant reduction in
      the number of breakthrough fungal infections disappeared when patients
      arbitrarily excluded from the analysis by the trial authors were included. In the
      second trial, the deoxycholate preparation of amphotericin B was used without any
      indication of the use of premedication to counter side effects and replacement of
      electrolytes or use of salt water. This choice of comparator resulted in a marked
      difference in the duration of treatment on the trial drugs (77 days with
      voriconazole versus 10 days with amphotericin B) and precluded meaningful
      comparisons of the benefits and harms of the two drugs. The third trial failed to
      find a difference in fungal free survival or invasive fungal infections at 180
      days when voriconazole was compared to fluconazole. AUTHORS' CONCLUSIONS:
      Liposomal amphotericin B is significantly more effective than voriconazole for
      empirical therapy of fungal infections in neutropenic cancer patients and should
      be preferred. For treatment of aspergillosis, there are no trials that have
      compared voriconazole with amphotericin B given under optimal conditions. For
      prophylactic fungal treatment in patients receiving allogeneic stem cell
      transplantation, there was no difference between voriconazole and fluconazole
      regarding fungal free survival or invasive fungal infections.

PMID- 24563223
TI  - What does general paediatric surgery involve? An audit of paediatric cases in 1
      year.
AB  - BACKGROUND: As all tertiary paediatric hospitals are based in the capital of
      Dublin, it is therefore necessary for general surgeons in centres outside of
      Dublin to undertake routine elective and emergency paediatric surgery to provide
      children with care close to home. The aim of this study is to assess the volume
      and type of procedures this entails. METHODS: Prospective analysis of the
      elective and emergency paediatric surgical services provided by a single surgeon
      in a regional university hospital to determine the volume and nature of general
      paediatric operative procedures performed. RESULTS: There were 126 operative
      procedures performed on patients less than 16 years of age during a 12-month
      period, accounting for 22.8 % of all operations. There were 56 emergency (44.4 %)
      and 70 elective procedures (55.5 %). The median age was 4.7 years (median age for
      emergencies 5.4 years, median age for elective surgery 3.8 years). Paediatric
      operations accounted for 23.4 % of all emergency and 26.2 % of all elective
      operations. The most commonly performed emergency operations were
      appendicectomies and pyloromyotomies, representing 73 % of all emergency cases.
      Inguinal hernia repair, excision of ingrown toenail and percutaneous endoscopic
      gastrostomy (PEG) tube insertion represented 61 % of elective procedures.
      CONCLUSIONS: The range of procedures in general paediatric surgery is small with
      only five procedures representing the majority of all elective and emergency
      procedures performed. This suggests that a period of specialist paediatric
      surgery training would enable more general surgeons to provide this vital
      service.

PMID- 24563224
TI  - The interaction of dipole modifiers with amphotericin-ergosterol complexes.
      Effects of phospholipid and sphingolipid membrane composition.
AB  - The influence of agents, known to affect the membrane dipole potential, phloretin
      and RH 421, on the multi channel activity of amphotericin B in lipid bilayers of
      various compositions, was studied. It was shown that the effects were dependent
      on the membrane's phospholipid and sphingolipid type. Phloretin enhanced
      amphotericin B induced steady-state transmembrane current through bilayers made
      from binary mixtures of POPC (DOPC) and ergosterol and ternary mixture of DPhPC,
      ergosterol and stearoylphytosphingosine. RH 421 increased steady-state polyene
      induced transmembrane current through membranes made from binary mixtures of
      DPhPC (DPhPS) and ergosterol and ternary mixture of DPhPS, ergosterol and
      stearoylphytosphingosine. It was proposed that the observed effects reflect the
      fine balance of the interactions between the various components present:
      amphotericin B, ergosterol, phospholipid, sphingolipid and dipole modifier. The
      shape of lipid molecules seems to be an important factor impacting the responses
      of amphotericin B modified bilayers to dipole modifiers. The influence of
      different phospholipids and sphingolipids on the physical and structural
      properties of ordered lipid microdomains, enriched in AmB, was also discussed. It
      was also shown that RH 421 enhanced the antifungal activity of amphotericin B in
      vitro.

PMID- 24563225
TI  - Apigenin induces apoptosis by targeting inhibitor of apoptosis proteins and Ku70
      Bax interaction in prostate cancer.
AB  - Dysfunction of the apoptotic pathway in prostate cancer cells confers apoptosis
      resistance towards various therapies. A novel strategy to overcome resistance is
      to directly target the apoptotic pathway in cancer cells. Apigenin, an anticancer
      agent, selectively toxic to cancer cells induces cell cycle arrest and apoptosis
      through mechanisms which are not fully explored. In the present study we provide
      novel insight into the mechanisms of apoptosis induction by apigenin. Treatment
      of androgen-refractory human prostate cancer PC-3 and DU145 cells with apigenin
      resulted in dose-dependent suppression of XIAP, c-IAP1, c-IAP2 and survivin
      protein levels. Apigenin treatment resulted in significant decrease in cell
      viability and apoptosis induction with the increase of cytochrome C in time
      dependent manner. These effects of apigenin were accompanied by decrease in Bcl
      xL and Bcl-2 and increase in the active form of Bax protein. The apigenin
      mediated increase in Bax was due to dissociation of Bax from Ku70 which is
      essential for apoptotic activity of Bax. Apigenin treatment resulted in the
      inhibition of class I histone deacetylases and HDAC1 protein expression, thereby
      increasing the acetylation of Ku70 and the dissociation of Bax resulting in
      apoptosis of cancer cells. Furthermore, apigenin significantly reduced HDAC1
      occupancy at the XIAP promoter, suggesting that histone deacetylation might be
      critical for XIAP downregulation. These results suggest that apigenin targets
      inhibitor of apoptosis proteins and Ku70-Bax interaction in the induction of
      apoptosis in prostate cancer cells and in athymic nude mouse xenograft model
      endorsing its in vivo efficacy.

PMID- 24563228
TI  - Structure-critical distribution of aromatic residues in the fibronectin type III
      protein family.
AB  - Over a thousand individual Fibronectin type III (FnIII) domain sequences,
      extracted from more than 60 different FnIII-dependent protein super-structures,
      were downloaded from curated database resources. Three regions of extreme
      sequence conservation within the well-characterized FnIII beta-sandwich structure
      were respectively defined by near absolute conservation of a tryptophan (Trp) in
      beta-strand-B, tyrosines (Tyr) in both beta-strand-C and beta-strand-F, and a
      leucine (Leu) residue in the unstructured region immediately preceding beta
      strand-F. Employing these four conserved landmarks, the entire FnIII sequence
      dataset was vertically registered to align the three conserved regions, and the
      cumulative distribution of all other amino acid functionality was determined and
      plotted relative to these landmark residues. Conserved aromatic sites were each
      found to be flanked by aliphatic residues that assure localization of these sites
      to the inaccessible hydrophobic interface between major sheet structures. Mapping
      the location of conserved aromatic sites in numerous PDB structures demonstrated
      the consistent pair-wise co-localization of the indole side-chain of the
      conserved strand-B Trp site to within 0.35 nm of the phenolic side-chain of the
      strand-C Tyr site located 8-14 amino acids distal. Likewise, the side-chain of
      the strand-F Tyr site co-localized to within 0.45 nm of the aliphatic side-chain
      of the conserved Leu that uniformly precedes it by six residues. While classic
      hydropathy-based theories would deem the "burying" of Tyr and Trp side-chains
      and/or their association with hydrophobic FnIII core residues thermodynamically
      unnecessary, alternative contributions of conserved Trp and Tyr residues, and
      particularly the role of the absolutely conserved tyrosine phenolic -OH in native
      FnIII structure-function are considered. A more global role for conserved FnIII
      aromaticity is also discussed in light of the aromatic conservation observed in
      other well-established protein families.

PMID- 24563227
TI  - Developmental increase in ecto-5'-nucleotidase activity overlaps with appearance
      of two immunologically distinct enzyme isoforms in rat hippocampal synaptic
      plasma membranes.
AB  - Ecto-5'-nucleotidase (e-5NT), a glycosylphosphatidylinositol-linked membrane
      protein, catalyzes a conversion of AMP to adenosine, which influences nearly
      every aspect of brain physiology, including embryonic and postnatal brain
      development. The present study aimed to investigate a pattern of expression,
      activity and kinetic properties of e-5NT in the hippocampal formation and
      synaptic plasma membrane (SPM) preparations in rats at postnatal days (PDs) 7,
      15, 20, 30 and 90. By combining gene expression analysis and enzyme
      histochemistry, we observed that e-5NT mRNA reached the adult level at PD20,
      while the enzyme activity continued to increase beyond this age. Further analysis
      revealed that hippocampal layers rich in synapses expressed the highest levels of
      e-5NT activity, while in layers populated with neuronal cell bodies, the enzyme
      activity was weak or absent. Therefore, activity and expression of e-5NT were
      analyzed in SPM preparations isolated from rats at different ages. The presence
      of two protein bands of about 65 and 68 kDa was determined by immunoblot
      analysis. The 65-kDa band was present at all ages, and its abundance increased
      from PD7 to PD20. The 68-kDa band appeared at PD15 and increased until PD30,
      coinciding with the increase of e-5NT activity, substrate affinity and enzymatic
      efficiency. Since distinct e-5NT isoforms may derive from different patterns of
      the enzyme protein N-glycosylation, we speculate that long-term regulation of e
      5NT activity in adulthood may be effectuated at posttranslational level and
      without overall change in the gene and protein expression.

PMID- 24563229
TI  - Residual feed intake as a feed efficiency selection tool and its relationship
      with feed intake, performance and nutrient utilization in Murrah buffalo calves.
AB  - Residual feed intake (RFI) is the difference between the actual and expected feed
      intake of an animal based on its body weight and growth rate over a specific
      period. The objective of this study was to determine the RFI of buffalo calves
      using residuals from appropriate linear regression models involving dry matter
      intake (DMI), average daily gain (ADG) and mid-test metabolic body weight.
      Eighteen male Murrah buffalo calves of 5-7 months were selected and fed
      individually. A feeding trial using ad libitum feeding of total mixed ration
      (TMR, concentrate/roughage = 40:60) was conducted for 52 days in which the daily
      DMI, weekly body weight (BW) and growth rate of the calves were monitored. RFI of
      calves ranged from -0.20 to +0.23 kg/day. Mean DMI (in grams per kilogram of
      BW(0.75)) during the feeding trial period was significantly (P < 0.05) lower in
      low RFI group (79.66 g/kg BW(0.75)) compared to high RFI (87.74 g/kg BW(0.75)).
      Average initial BW, final BW and mid-test BW(0.75) did not differ (P > 0.05)
      between low and high RFI groups. Over the course of a trial period, low RFI group
      animals consumed 10% less feed compared to high RFI group of animals, yet
      performed in a comparable manner in terms of growth rate. Metabolizable energy
      for maintenance (MEm) was found to be significantly (P < 0.05) lower in low RFI
      group (13.54 MJ/100 kg BW) as compared to that of high RFI group (15.56 MJ/100 kg
      BW). The present study indicates that RFI is a promising selection tool for the
      selection of buffaloes for increased feed efficiency.

PMID- 24563226
TI  - Hippocampal glycogen synthase kinase 3beta is critical for the antidepressant
      effect of cyclin-dependent kinase 5 inhibitor in rats.
AB  - Cdk5 is a member of cyclin-dependent kinase (Cdk), a proline-directed
      serine/threonine kinase, and plays a key role in normal neural development and
      function. Evidence of previous study showed that chronic inhibition of Cdk5 in
      hippocampal dentate gyrus (DG) blocked the development of depressive-like
      symptoms, suggesting that Cdk5 plays a role in development of depression. Forced
      swim test, novelty-suppressed feeding test, and learned helplessness were used to
      evaluate the cellular and molecular mechanisms underlying the behavioral
      regulation of Cdk5 inhibitors in rats. Two Cdk5 inhibitors butyrolactone and
      roscovitine were used to investigate the possible antidepressant-like actions of
      Cdk5 blockade and the potential mechanisms. Systemic administration of
      butyrolactone (200 mg/kg, IP) or roscovitine (100 mg/kg, IP) produced effective
      antidepressant-like actions. Moreover, infusion (5 mM) of GSK3beta activator
      LY294002 into DG abolished the antidepressant-like actions of butyrolactone and
      roscovitine, suggesting that inhibition of GSK3beta might be involved in the
      antidepressant effect of Cdk5 inhibitors. Moreover, pretreatment of LY294002 (5
      mM) blocked the antidepressant-like effect of butyrolactone and roscovitine in
      learned helplessness. Additionally, inescapable footshock induced a significant
      increase of GSK3beta activity, while butyrolactone and roscovitine decreased
      GSK3beta activity. In contrast, pretreatment of LY294002 prevented the inhibitory
      effects of butyrolactone and roscovitine on GSK3beta activation. Finally, a
      specific GSK3beta inhibitor, SB216763 (1 ng, DG), demonstrated an effective
      antidepressant-like action. These findings demonstrate that systemic
      administration of Cdk5 inhibitors produced antidepressant-like actions and that
      inhibition of GSK3beta is involved in behavioral response of Cdk5 inhibitors.

PMID- 24563232
TI  - Association of genetic polymorphisms in HSD17B1, HSD17B2 and SHBG genes with
      hepatocellular carcinoma risk.
AB  - Genetic polymorphisms of enzymes involved in estrogen synthesizing/transporting
      can influence the risk of hormone-dependent diseases. The incidence rate and
      relative risk for hepatocellular carcinoma (HCC) are higher in men than in women.
      This study was conducted to explore the relationship of single nucleotide
      polymorphisms (SNPs) in 17 beta-Hydroxysteroid dehydrogenases (HSD17B1 and
      HSD17B2) and sex hormone-binding globulin (SHBG) genes with the risk of HCC
      within Chinese Han population. Polymorphisms of HSD17B1 rs676387, HSD17B2
      rs8191246 and SHBG rs6259 were genotyped in 253 HCC patients and 438 healthy
      control subjects using the polymerase chain reaction-restriction fragment length
      polymorphism (PCR-RFLP). Significantly increased HCC risk was found to be
      associated with T allele of rs676387 and G allele of rs8191246. Increased HCC
      risks were found in different genetic model (TT genotype in a recessive model, T
      allele carriers in a dominant model, TT genotype and TG genotype in a codominant
      model for HSD17B1 rs676387, G allele carriers in a dominant model and AG genotype
      in a codominant model for HSD17B2 rs8191246, respectively). No association
      between SHBG rs6259 and HCC risk was observed. The present study provided
      evidence that HSD17B1 rs676387 and HSD17B2 rs8191246 were association with HCC
      development. Further studies in diverse ethnic population with larger sample size
      were recommended to confirm the findings. 

PMID- 24563233
TI  - Possible prognostic value of BORIS transcript variants ratio in laryngeal
      squamous cell carcinomas - a pilot study.
AB  - BORIS is a paralog of a highly conserved, multi-functional chromatin factor CTCF.
      Unlike CTCF, which has been shown to possess tumor-suppressive properties, BORIS
      belongs to the "cancer/testis antigen" family normally expressed only in germ
      cells and aberrantly activated in a variety of tumors. The consequences of BORIS
      expression, relative abundance of its isoforms, and its role in carcinogenesis
      have not been completely elucidated. It activates transcription of hTERT and MYC,
      genes relevant for laryngeal carcinoma progression. In this study, BORIS
      expression has been analyzed at the transcriptional level by RT-PCR and protein
      level by semi-quantitative immunohistochemistry in 32 laryngeal squamous cell
      carcinomas and adjacent non-tumorous tissue. BORIS was detected in 44 % (14/32)
      laryngeal squamous cell carcinoma samples, while it was detected only in one
      normal, tumor-adjacent tissue sample. Tree based survival analysis, using the
      recursive partitioning algorithm mvpart, extracted the ratio of relative
      abundance of BORIS transcript variants containing exon 7 (BORIS 7+) and those
      lacking exon 7 (BORIS 7-) as an independent prognostic factor associated with
      disease relapse during a 5-year follow-up period. Patients having BORIS 7+/BORIS
      7- ratio >=1 had a higher rate of disease relapse than patients with BORIS
      7+/BORIS 7- ratio <1. Hazard ratio for that group, based on Cox Proportional
      Hazard Regression, was 3.53. This is the first study analyzing expression of
      BORIS protein and transcript variants in laryngeal squamous cell carcinoma
      relative to its possible prognostic value for recurrence and overall survival.

PMID- 24563234
TI  - Intima/medulla reconstruction and vascular contraction-relaxation recovery for
      acellular small diameter vessels prepared by hyperosmotic electrolyte solution
      treatment.
AB  - This study aims at the evaluation of blood vessel reconstruction process of
      decellularized small diameter vessels prepared by a hyperosmotic electrolyte
      solution treatment not only histologically but also physiologically in rat
      transplantation model. Complete cell removal by a hyperosmotic electrolyte
      solution treatment was confirmed by hematoxylin/eosin staining and scanning
      electron microscopic observation. All acellular vessels transplanted into the rat
      abdominal aorta were patent up to 14 months. One week post-transplantation, the
      vWF-positive cells were observed on the luminal surface but the layer formation
      did not complete. Five weeks following transplantation, the vWF-positive
      endothelial cells were located on the intima consistent with intact endothelial
      cells. Beneath the endothelial cells, alpha-SMA-positive smooth muscle cells were
      distributed. The harvested vessels displayed formation of tunica intima
      (endothelial cells) and tunica medulla (smooth muscle cell) layers. We also
      examined the physiological properties of the vessels 12 months post
      transplantation using a wire myograph system. The transplanted vessels contracted
      upon addition of norepinephrine and relaxed upon addition of sodium nitroprusside
      as well as the native vessels. In conclusion, the acellular vessels prepared with
      hyperosmotic electrolytic solution showed excellent and long-term patency, which
      may be related to the successful preservation of vascular ECM. In addition, the
      acellular vessels revealed the intima/medulla regeneration with the physiological
      contraction-relaxation functions in response to the each substance. 

PMID- 24563235
TI  - Significant and safe shortening of the recovery time after flumazenil-reversed
      midazolam sedation.
AB  - BACKGROUND: Endoscopy under midazolam sedation requires a 2-h recovery facility.
      AIM: To study the potential of shortening patients' stay without jeopardizing
      patients' safety by the use of the benzodiazepine-antagonist flumazenil in the
      everyday practice and to investigate the feasibility of a study comparing
      midazolam with recovery with midazolam-flumazenil and immediate discharge.
      METHODS: Consecutive ambulatory patients referred for endoscopy under midazolam
      sedation with ASA I or II, escorted by a person, were eligible. Flumazenil was
      given on arrival in the recovery room. Patients were discharged when adequate
      Aldrete scores and physical mobility were present. The next day, they were
      contacted by telephone. RESULTS: A total of 1,506 patients participated. They
      received 5 mg midazolam, while 887 patients also received 50 mcg fentanyl. The
      median dose of flumazenil was 0.2 mg. Oxygen desaturation (sO2 <92%) occurred in
      15% during the procedure without an effect on recovery and discharge times.
      Patients left the department 65 min after the last midazolam administration. The
      majority (82.7%) were fully alert during their journey home. At home, 2.7% went
      to bed, 45.2% took a nap, and 40% undertook activities. Almost every patient
      (98.8%) liked the shortened recovery time. Three patients had an incident
      (fainting, fall, and near-fall) without consequences. Based on this low
      incidence, a non-inferiority comparison of midazolam-flumazenil with midazolam
      recovery would require a total of 32,650 patients. CONCLUSIONS: Administration of
      flumazenil resulted in a safe shortening of the recovery period and offers the
      possibility for substantial savings in time, space, and nurse resources. A non
      inferiority comparison will not be practicable.

PMID- 24563236
TI  - Prevalence of Helicobacter pylori infection worldwide: a systematic review of
      studies with national coverage.
AB  - The systematic assessment of large population-based surveys addressing the
      prevalence of Helicobacter pylori infection may provide robust evidence for
      understanding the trends in the exposure to this major risk factor across
      settings with distinct patterns of gastric cancer variation. Our aim was to
      describe the prevalence of H. pylori infection in different countries and
      periods, through systematic review of the literature. We searched PubMed from
      inception up to September 2013 to identify original studies reporting on the
      prevalence of H. pylori, and only those evaluating samples with national coverage
      were included. We identified 37 eligible studies including data for 22 countries.
      The prevalences were higher in Central/South America and Asia, and at least two
      fold higher in countries with high gastric cancer incidence. In most countries
      presenting data for different time periods, the prevalences were usually lower in
      the most recent surveys. However, there was little variation in settings where
      prevalences were already low. Among countries with high prevalence of H. pylori
      infection there is an ample scope for reducing its burden in the next decades,
      whereas further declines in settings with already low prevalences will require
      more intensive efforts. 

PMID- 24563238
TI  - Endoscopic papillary balloon dilation versus sphincterotomy for removal of small
      common bile duct stones in young patients: unresolved issues for an expanding
      technique.

PMID- 24563237
TI  - Fractal analysis of contrast-enhanced CT images to predict survival of patients
      with hepatocellular carcinoma treated with sunitinib.
AB  - BACKGROUND: Intratumoral heterogeneity is a well-recognized feature of
      malignancy. AIMS: To assess the heterogeneity of tumor using fractal analysis of
      contrast-enhanced computed tomography (CE-CT) images for predicting survival of
      hepatocellular carcinoma (HCC) patients treated with sunitinib. METHODS: The
      patient cohort comprised 23 patients (19 men, 4 women; mean age 61.5 years) with
      HCC who underwent CE-CT at baseline and after one cycle of sunitinib. Arterial
      phase (AP) and portal-phase (PP) CE-CT images were analyzed using a plugin
      software for ImageJ (NIH, Bethesda, MD). A differential box-counting method was
      employed to calculate the fractal dimension (FD) of the tumor. Tumor FD, density,
      and size were compared with survival. RESULTS: Median progression-free survival
      (PFS) was 4.43 months. Patients were grouped into a favorable PFS (PFS >4.43
      months; 9 patients) and an unfavorable PFS group (PFS <= 4.43; 13 patients). The
      baseline FD on both the AP and PP images was lower in the favorable PFS group
      than in the unfavorable PFS group (both P = 0.03). There was a significant
      difference in the change of the FD on the AP image between the favorable and
      unfavorable PFS groups (P = 0.02). Tumor density and size showed no significant
      correlations with PFS. In the Kaplan-Meier analysis, patients with tumors showing
      lower FD on the AP image at baseline showed longer PFS (P = 0.002). Patients with
      tumors showing a greater reduction in the FD on the PP image after one cycle of
      the therapy showed longer overall survival (P = 0.002). CONCLUSION: The FD of the
      tumor on CE-CT images may be a useful biomarker for HCC patients treated with
      sunitinib.

PMID- 24563240
TI  - Implementation of online suicide-specific training for VA providers.
AB  - OBJECTIVE: Due to the gap in suicide-specific intervention training for mental
      health students and professionals, e-learning is one solution to improving
      provider skills in the Veterans Affairs (VA) health system. This study focused on
      the development and evaluation of an equivalent e-learning alternative to the
      Collaborative Assessment and Management of Suicidality (CAMS) in-person training
      approach at a Veteran Health Affairs medical center. METHODS: The study used a
      multicenter, randomized, cluster, and three group design. the development of e
      CAMS was an iterative process and included pilot testing. Eligible and consenting
      mental health providers, who completed a CAMS pre-survey, were randomized.
      Provider satisfaction was assessed using the standard VA evaluation of training
      consisting of 20 items. Two post training focus groups, divided by learning
      conditions, were conducted to assess practice adoption using a protocol focused
      on experiences with training and delivery of CAMS. RESULTS: A total of 215
      providers in five sites were randomized to three conditions: 69 to e-learning, 70
      to in-person, 76 to the control. The providers were primarily female, Caucasian,
      midlife providers. Based on frequency scores of satisfaction items, both learning
      groups rated the trainings positively. In focus groups representing divided by
      learning conditions, participants described positive reactions to CAMS training
      and similar individual and institutional barriers to full implementation of CAMS.
      CONCLUSIONS: This is the first evaluation study of a suicide-specific e-learning
      training within the VA. The e-CAMS appears equivalent to the in-person CAMS in
      terms of provider satisfaction with training and practice adoption, consistent
      with other comparisons of training deliveries across specialty areas. Additional
      evaluation of provider confidence and adoption and patient outcomes is in
      progress. The e-CAMS has the potential to provide ongoing training for VA and
      military mental health providers and serve as a tutorial for psychiatrists in
      preparation for specialty boards.

PMID- 24563241
TI  - Residents and faculty work together to reduce faculty intimidation of residents
      and improve morale.

PMID- 24563239
TI  - Plasma triglyceride levels may modulate hepatitis C viral replication.
AB  - BACKGROUND: Plasma and hepatic lipid abnormalities are frequent in hepatitis C
      infected individuals. METHODS: Plasma lipid and medical records profiles were
      prospectively obtained in 130 consecutive individuals seen by a single
      hepatologist in a university liver disease clinic. The relationships between
      viral load, genotype, plasma lipid fractions, HDL, LDL particle number and
      particle size were examined. RESULTS: Of 130 individuals studied, 74 had
      hepatitis C while 15 had NAFLD/NASH and 30 had alcohol related liver disease. The
      LDL particle number and LDL-C levels did not differ between those with and
      without hepatitis C although the number of small LDL particles was greater in
      those with hepatitis C infection. The HDL-C and total cholesterol levels were
      greater in those without hepatitis C than those with hepatitis C (P = 0.009). In
      contrast, the serum triglyceride level was greater in the hepatitis C viral group
      (P = 0.013). Importantly, the hepatitis C viral load regardless of the genotype
      correlated directly with the triglyceride and VLDL levels with r values of 0.73
      and 0.84, respectively. CONCLUSIONS: There are: (1) important differences in
      lipid classes, number and the size of lipid particles exist between hepatitis C
      virus infected and noninfected liver disease groups, (2) the serum total
      triglyceride and the LDL levels correlate significantly with the hepatitis C
      viral load and, (3) Serum triglyceride level may play an important role in viral
      replication. These data further suggest that therapies directed at lowering
      plasma triglyceride levels may enhance the efficacy of current antiviral
      treatment regimens.

PMID- 24563242
TI  - Using Audience Response System technology and PRITE questions to improve
      psychiatric residents' medical knowledge.
AB  - OBJECTIVE: Interactive educational tools are thought to convey material
      effectively. Audience Response Systems (ARSs), in particular, have been shown to
      improve written test scores in several residency fields but have not been
      previously reported in psychiatry. Such an approach may prove a valuable tool in
      improving test performance and medical knowledge. METHODS: Psychiatry residents
      were required to attend 12 90-min review sessions throughout the summer that
      utilized previous Psychiatry Residency In-Training Exam (PRITE) questions and an
      ARS to provide immediate feedback and a stimulus for discussion. Preparation for
      these sessions was either unsupervised (phase I) or involved a personalized
      reading program for residents who scored below the 50th percentile. Data were
      evaluated with ANOVA and unpaired 2-tail tests. RESULTS: Overall performance on
      the PRITE examination improved significantly as compared to pre-intervention
      controls (change in score 17.0 +/- SD 16.6 vs 6.4 +/- 12.6, P = 0.0068). The
      addition of a personalized reading program did not improve raw score performance
      significantly beyond the improvement seen with ARS alone but did slightly improve
      percentile rank and STD score. CONCLUSIONS: Utilization of the interactive ARS
      may improve performance on PRITE examination for residents.

PMID- 24563243
TI  - Genetic mapping of the labile (lab) gene: a recessive locus causing irregular
      spikelet fertility in labile-barley (Hordeum vulgare convar. labile).
AB  - KEY MESSAGE: The recessive labile locus mapped on chromosome 5HL causes irregular
      spikelet fertility and controls floret development as well as row-type in barley.
      The labile-barley displays a variable number of fertile spikelets at each rachis
      internode (0-3 fertile spikelets/rachis internode) which is intermediate between
      that observed in two- or six-rowed types. Previous re-sequencing of Vrs1 in 219
      labile-barley (Hordeum vulgare L. convar. labile) accessions showed that all
      carried a six-rowed specific allele. We therefore hypothesized that this
      seemingly random reduction in spikelet fertility is most likely caused by the
      labile (lab) locus, which we aimed to phenotypically and genetically define.
      Here, we report a detailed phenotypic analysis of spikelet fertility in labile
      barleys in comparison to two- and six-rowed genotypes using scanning electron
      microscopy analysis. We found that the first visible morphological deviation
      occurred during the stamen primordium stage, when we regularly observed the
      appearance of arrested central floral primordia in labile but not in two- or six
      rowed barleys. At late stamen and early awn primordium stages, lateral florets in
      two-rowed and only some in labile-barley showed retarded development and
      reduction in size compared with fully fertile lateral florets in six-rowed
      barley. We used two F2 mapping populations to generate whole genome genetic
      linkage maps and ultimately locate the lab locus as a recessive Mendelian trait
      to a 4.5-5.8 cM interval at approximately 80 cM on chromosome 5HL. Our results
      will help identifying the role of the lab gene in relation to other spikelet
      fertility factors in barley.

PMID- 24563244
TI  - Intraprocedural contrast-enhanced ultrasound (CEUS) in liver percutaneous
      radiofrequency ablation: clinical impact and health technology assessment.
AB  - OBJECTIVES: To assess the clinical and the economic impacts of intraprocedural
      use of contrast-enhanced ultrasound (CEUS) in patients undergoing percutaneous
      radiofrequency ablation for small (<2.5 cm) hepatocellular carcinomas. METHODS:
      One hundred and forty-eight hepatocellular carcinomas in 93 patients were treated
      by percutaneous radiofrequency ablation and immediate assessment by
      intraprocedural CEUS. Clinical impact, cost effectiveness, and budget,
      organisational and equity impacts were evaluated and compared with standard
      treatment without intraprocedural CEUS using the health technology assessment
      approach. RESULTS: Intraprocedural CEUS detected incomplete ablation in 34/93
      (36.5 %) patients, who underwent additional treatment during the same session. At
      24-h, complete ablation was found in 88/93 (94.6 %) patients. Thus, a second
      session of treatment was spared in 29/93 (31.1 %) patients. Cost-effectiveness
      analysis revealed an advantage for the use of intraprocedural CEUS in comparison
      with standard treatment (4,639 vs 6,592) with a 21.9 % reduction of the costs to
      treat the whole sample. Cost per patient for complete treatment was <euro> 4,609
      versus <euro> 5,872 respectively. The introduction of intraprocedural CEUS
      resulted in a low organisational impact, and in a positive impact on equity
      CONCLUSIONS: Intraprocedural use of CEUS has a relevant clinical impact, reducing
      the number of re-treatments and the related costs per patient. TEACHING POINTS: *
      CEUS allows to immediately asses the result of ablation. * Intraprocedural CEUS
      decreases the number of second ablative sessions. * Intraprocedural CEUS may
      reduce cost per patient for complete treatment. * Use of intraprocedural CEUS may
      reduce hospital budget. * Its introduction has low organisational impact, and
      relevant impact on equity.

PMID- 24563245
TI  - Thermotaxis navigation behavior.
AB  - This chapter describes four different protocols used to assay thermotaxis
      navigation behavior of single, or populations of, C. elegans hermaphrodites on
      spatial thermal gradients within the physiological temperature range (15-25
      degrees C). A method to assay avoidance of noxious temperatures is also
      described. 

PMID- 24563246
TI  - Evaluation of Pediatric Bleeding Questionnaire in Turkish Children With Von
      Willebrand Disease and Platelet Function Disorders.
AB  - The diagnosis of mild bleeding disorders is not easy as most of the "healthy"
      individuals also report bleeding symptoms. In order to get a precise bleeding
      history, Pediatric Bleeding Questionnaire (PBQ) has been developed. In our study,
      Turkish children diagnosed with Von Willebrand disease (VWD), platelet function
      defect (PFD), and healthy children without any symptoms (control group 1) and
      healthy children with symptoms but found hemostatically normal (control group 2)
      were analyzed with PBQ. The cut off level for "positive bleeding score" was found
      to be >=2 (area under the curve [AUC]: 0.785, 95% confidence interval [CI]: 0.718
      0.852). The sensitivity, specificity, positive predictive value, and negative
      predictive value of PBQ to define VWD versus control group 1 was 100%, 97.4%,
      96.4%, and 100%; VWD versus control group 2 was 100%, 53.1%, 64.3%, and 100%; PFD
      versus control group 1 was 93.3%, 53.1%, 73.7%, and 85%; and PFD versus control
      group 2 was 93.3%, 53.1%, 73.7%, and 85%, respectively. 

PMID- 24563247
TI  - Postmarketing Surveillance of Recombinant Human Soluble Thrombomodulin
      (Thrombomodulin alpha) in Pediatric Patients With Disseminated Intravascular
      Coagulation.
AB  - Recombinant human soluble thrombomodulin (thrombomodulin alpha [TM-alpha]) has
      been marketed as a novel anticoagulant for disseminated intravascular coagulation
      (DIC) in Japan since 2008. Postmarketing surveillance (PMS) has been conducted
      since its approval. As effectiveness and safety were not previously determined in
      pediatric patients, this study evaluated PMS data and examined the usefulness of
      TM-alpha in treating pediatric DIC. After excluding newborn infants, data for 210
      pediatric patients were analyzed and compared to 3786 adult patients. The day
      after the last TM-alpha administration, DIC had resolved in 58.5% of the
      patients. At 28 days after the last TM-alpha administration, the survival rate
      was 71.6%. Nineteen episodes of adverse drug reactions were observed in 11
      patients but no significant differences were noted for effectiveness and safety.
      Although this study was limited by its retrospective design, including selection
      biases and no limitation on concomitant use of other anticoagulants, TM-alpha
      appears to be useful for the treatment of DIC in both pediatric and adult
      patients. 

PMID- 24563250
TI  - Living donor lobar lung transplantation: a longstanding concept being revisited
      with the same old NEMESIS.
AB  - INTRODUCTION: Living donor lobar lung transplantation (LDLLT) has been
      successfully used in select patient populations. MATERIALS AND METHODS: A 29-year
      old male, who underwent bilateral LDLLT 12 years earlier with allografts donated
      by father and paternal uncle, developed bronchiolitis obliterans syndrome at
      distinctly different rates. CONCLUSION: LDLLT can be done successfully with
      unique management issues.

PMID- 24563249
TI  - Overexpression of rice OsREX1-S, encoding a putative component of the core
      general transcription and DNA repair factor IIH, renders plant cells tolerant to
      cadmium- and UV-induced damage by enhancing DNA excision repair.
AB  - Screening of 40,000 Arabidopsis FOX (Full-length cDNA Over-eXpressor gene hunting
      system) lines expressing rice full-length cDNAs brings us to identify four
      cadmium (Cd)-tolerant lines, one of which carried OsREX1-S as a transgene. OsREX1
      S shows the highest levels of identity to Chlamydomonas reinhardtii REX1-S
      (referred to as CrREX1-S, in which REX denotes Required for Excision) and to
      yeast and human TFB5s (RNA polymerase II transcription factor B5), both of which
      are components of the general transcription and DNA repair factor, TFIIH.
      Transient expression of OsREX1-S consistently localized the protein to the
      nucleus of onion cells. The newly generated transgenic Arabidopsis plants
      expressing OsREX1-S reproducibly displayed enhanced Cd tolerance, confirming that
      the Cd-tolerance of the initial identified line was conferred solely by OsREX1-S
      expression. Furthermore, transgenic Arabidopsis plants expressing OsREX1-S
      exhibited ultraviolet-B (UVB) tolerance by reducing the amounts of cyclobutane
      pyrimidine dimers produced by UVB radiation. Moreover, those transgenic OsREX1-S
      Arabidopsis plants became resistant to bleomycin (an inducer of DNA strand break)
      and mitomycin C (DNA intercalating activity), compared to wild type. Our results
      indicate that OsREX1-S renders host plants tolerant to Cd, UVB radiation,
      bleomycin and mitomycin C through the enhanced DNA excision repair. 

PMID- 24563251
TI  - Discrimination of the Acinetobacter calcoaceticus-Acinetobacter baumannii complex
      species by Fourier transform infrared spectroscopy.
AB  - The main goal of this work was to assess the ability of Fourier transform
      infrared spectroscopy with attenuated total reflectance (FTIR-ATR) to
      discriminate between the species of the Acinetobacter calcoaceticus-Acinetobacter
      baumannii (Acb) complex, i.e. A. baumannii, A. nosocomialis, A. pittii, A.
      calcoaceticus, genomic species "Between 1 and 3" and genomic species "Close to
      13TU". A total of 122 clinical isolates of the Acb complex previously identified
      by rpoB sequencing were studied. FTIR-ATR spectra was analysed by partial least
      squares discriminant analysis (PLSDA) and the model scores were presented in a
      dendrogram form. This spectroscopic technique proved to be effective in the
      discrimination of the Acb complex species, with sensitivities from 90 to 100%.
      Moreover, a flowchart aiming to help with species identification was developed
      and tested with 100% correct predictions for A. baumannii, A. nosocomialis and A.
      pittii test isolates. This rapid, low cost and environmentally friendly technique
      proved to be a reliable alternative for the identification of these closely
      related Acinetobacter species that share many clinical and epidemiological
      characteristics and are often difficult to distinguish. Its validation towards
      application on a routine basis could revolutionise high-throughput bacterial
      identification.

PMID- 24563252
TI  - Distinct conformations of the chemokine receptor CCR4 with implications for its
      targeting in allergy.
AB  - CC chemokine receptor 4 (CCR4) is expressed by Th2 and regulatory T cells and
      directs their migration along gradients of the chemokines CCL17 and CCL22. Both
      chemokines and receptor are upregulated in allergic disease, making CCR4 a
      therapeutic target for the treatment of allergy. We set out to assess the
      mechanisms underlying a previous report that CCL22 is a dominant ligand of CCR4,
      which may have implications for its therapeutic targeting. Human T cells
      expressing endogenous CCR4 and transfectants engineered to express CCR4 were
      assessed for receptor function, using assays of calcium release, chemotaxis,
      receptor endocytosis, and ligand binding. Despite the two ligands having equal
      potency in calcium flux and chemotaxis assays, CCL22 showed dominance in both
      receptor endocytosis assays and heterologous competitive binding assays. Using
      two different CCR4-specific Abs, we showed that CCR4 exists in at least two
      distinct conformations, which are differentially activated by ligand. A major
      population is activated by both CCL17 and CCL22, whereas a minor population is
      activated only by CCL22. Mutation of a single C-terminal residue K310 within a
      putative CCR4 antagonist binding site ablated activation of CCR4 by CCL17, but
      not by CCL22, despite having no effect on the binding of either ligand. We
      conclude that CCL17 and CCL22 are conformationally selective ligands of CCR4 and
      interact with the receptor by substantially different mechanisms. This finding
      suggests that the selective blockade of CCR4 in allergy may be feasible when one
      CCR4 ligand dominates, allowing the inhibition of Th2 signaling via one ligand
      while sparing regulatory T cell recruitment via another. 

PMID- 24563254
TI  - Role of mouse and human autophagy proteins in IFN-gamma-induced cell-autonomous
      responses against Toxoplasma gondii.
AB  - IFN-gamma mediates cellular innate immunity against an intracellular parasite,
      Toxoplasma gondii, by inducing immunity-related GTPases such as p47 IFN-gamma
      regulated GTPases (IRGs) and p65 guanylate-binding proteins (GBPs), which also
      participate in antibacterial responses via autophagy. An essential autophagy
      protein, Atg5, was previously shown to play a critical role in anti-T. gondii
      cell-autonomous immunity. However, the involvement of other autophagy proteins
      remains unknown. In this study, we show that essential autophagy proteins
      differentially participate in anti-T. gondii cellular immunity by recruiting IFN
      gamma-inducible GTPases. IFN-gamma-induced suppression of T. gondii proliferation
      and recruitment of an IRG Irgb6 and GBPs are profoundly impaired in Atg7- or
      Atg16L1-deficient cells. In contrast, cells lacking other essential autophagy
      proteins, Atg9a and Atg14, are capable of mediating the anti-T. gondii response
      and recruiting Irgb6 and GBPs to the parasites. Although IFN-gamma also
      stimulates anti-T. gondii cellular immunity in humans, whether this response
      requires GBPs and human autophagy proteins remains to be seen. To analyze the
      role of human ATG16L1 and GBPs in IFN-gamma-mediated anti-T. gondii responses,
      human cells lacking ATG16L1 or GBPs were generated by the Cas9/CRISPR genome
      editing technique. Although both ATG16L1 and GBPs are dispensable for IFN-gamma
      induced inhibition of T. gondii proliferation in the human cells, human ATG16L1
      is also required for the recruitment of GBPs. Taken together, human ATG16L1 and
      mouse autophagy components Atg7 and Atg16L1, but not Atg9a and Atg14, participate
      in the IFN-gamma-induced recruitment of the immunity-related GTPases to the
      intracellular pathogen. 

PMID- 24563253
TI  - Mutational and structural analysis of KIR3DL1 reveals a lineage-defining
      allotypic dimorphism that impacts both HLA and peptide sensitivity.
AB  - Killer Ig-like receptors (KIRs) control the activation of human NK cells via
      interactions with peptide-laden HLAs. KIR3DL1 is a highly polymorphic inhibitory
      receptor that recognizes a diverse array of HLA molecules expressing the Bw4
      epitope, a group with multiple polymorphisms incorporating variants within the
      Bw4 motif. Genetic studies suggest that KIR3DL1 variation has functional
      significance in several disease states, including HIV infection. However, owing
      to differences across KIR3DL1 allotypes, HLA-Bw4, and associated peptides, the
      mechanistic link with biological outcome remains unclear. In this study, we
      elucidated the impact of KIR3DL1 polymorphism on peptide-laden HLA recognition.
      Mutational analysis revealed that KIR residues involved in water-mediated
      contacts with the HLA-presented peptide influence peptide binding specificity. In
      particular, residue 282 (glutamate) in the D2 domain underpins the lack of
      tolerance of negatively charged C-terminal peptide residues. Allotypic KIR3DL1
      variants, defined by neighboring residue 283, displayed differential
      sensitivities to HLA-bound peptide, including the variable HLA-B*57:01-restricted
      HIV-1 Gag-derived epitope TW10. Residue 283, which has undergone positive
      selection during the evolution of human KIRs, also played a central role in Bw4
      subtype recognition by KIR3DL1. Collectively, our findings uncover a common
      molecular regulator that controls HLA and peptide discrimination without
      participating directly in peptide-laden HLA interactions. Furthermore, they
      provide insight into the mechanics of interaction and generate simple, easily
      assessed criteria for the definition of KIR3DL1 functional groupings that will be
      relevant in many clinical applications, including bone marrow transplantation. 

PMID- 24563255
TI  - Inhibitory Fcgamma receptor is required for the maintenance of tolerance through
      distinct mechanisms.
AB  - The inhibitory FcgammaR FcgammaRIIB is widely expressed on B cells, dendritic
      cells (DCs), and myeloid effector cells and modulates a variety of Ab-driven in
      vivo functions. Although it has been established that FcgammaRIIB plays an
      important role in the maintenance of peripheral tolerance, the responsible cell
      specific FcgammaRIIB expression remains to be determined. In this study, we
      generated mice with selective deletion of FcgammaRIIB in B cells, DCs, and
      myeloid effector cells and evaluated these novel strains in models of tolerance
      and autoimmune diseases. Our results demonstrate that mice with selective
      deletion of FcgammaRIIB expression in B cells and DCs have increased Ab and T
      cell responses, respectively, and display enhanced susceptibility to disease in
      distinct models, suggesting that FcgammaRIIB expression in distinct cellular
      populations contributes to the maintenance of peripheral tolerance through
      different mechanisms. 

PMID- 24563257
TI  - Improved protein-ligand binding affinity prediction by using a curvature
      dependent surface-area model.
AB  - MOTIVATION: Hydrophobic effect plays a pivotal role in most protein-ligand
      binding. State-of-the-art protein-ligand scoring methods usually treat
      hydrophobic free energy as surface tension, which is proportional to interfacial
      surface area for simplicity and efficiency. However, this treatment ignores the
      role of molecular shape, which has been found very important by either
      experimental or theoretical studies. RESULTS: We propose a new empirical scoring
      function, named Cyscore. Cyscore improves the prediction accuracy by using a
      novel curvature-dependent surface-area model, which is able to distinguish
      convex, planar and concave surface in hydrophobic free energy calculation.
      Benchmark tests show that this model significantly improves the protein-ligand
      scoring and Cyscore outperforms a variety of well established scoring functions
      using PDBbind benchmark sets for binding affinity correlation and ranking tests.
      We expect the curvature-dependent surface-area model and Cyscore would contribute
      to the study of protein-ligand interactions. AVAILABILITY: Cyscore is available
      to non-commercial users at http://clab.labshare.cn/software/cyscore.html.

PMID- 24563258
TI  - Isolated hepatic sarcoidosis mimicking liver microabscesses: a case report.

PMID- 24563256
TI  - Influenza infection suppresses NADPH oxidase-dependent phagocytic bacterial
      clearance and enhances susceptibility to secondary methicillin-resistant
      Staphylococcus aureus infection.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) has emerged as a leading
      contributor to mortality during recent influenza pandemics. The mechanism for
      this influenza-induced susceptibility to secondary S. aureus infection is poorly
      understood. In this study, we show that innate antibacterial immunity was
      significantly suppressed during the recovery stage of influenza infection, even
      though MRSA superinfection had no significant effect on viral burdens. Compared
      with mice infected with bacteria alone, postinfluenza MRSA-infected mice
      exhibited impaired bacterial clearance, which was not due to defective phagocyte
      recruitment, but rather coincided with reduced intracellular reactive oxygen
      species levels in alveolar macrophages and neutrophils. NADPH oxidase is
      responsible for reactive oxygen species production during phagocytic bacterial
      killing, a process also known as oxidative burst. We found that gp91(phox)
      containing NADPH oxidase activity in macrophages and neutrophils was essential
      for optimal bacterial clearance during respiratory MRSA infections. In contrast
      to wild-type animals, gp91(phox-/-) mice exhibited similar defects in MRSA
      clearance before and after influenza infection. Using gp91(phox+/-) mosaic mice,
      we further demonstrate that influenza infection inhibits a cell-intrinsic
      contribution of NADPH oxidase to phagocyte bactericidal activity. Taken together,
      our results establish that influenza infection suppresses NADPH oxidase-dependent
      bacterial clearance and leads to susceptibility to secondary MRSA infection. 

PMID- 24563259
TI  - Malignancies associated with pregnancy: an analysis of 21 clinical cases.
AB  - AIM: This study aimed at investigating the clinical characteristics of
      malignancies associated with pregnancy and to provide information for the
      development of suitable strategies of treating maternal malignancies. METHODS: We
      conducted a retrospective analysis of 21 pregnant women with cancer who were
      admitted to our hospital between 2006 and 2012. The patients' clinical
      characteristics, treatment during pregnancy and postpartum, and pregnancy outcome
      were recorded. RESULTS: There were 21 cases of malignancies associated with
      pregnancy, including 6 cases of cervical cancer, 6 cases of breast cancer, 3
      cases of liver cancer, 2 cases of ovarian cancer, 2 cases of thyroid cancer, 1
      case of nasopharyngeal carcinoma, and 1 case of malignant brain tumor. Of the 21
      patients, 15 patients continued their pregnancies (9 of these patients received
      cancer treatment), whereas the other 6 terminated pregnancy. The modes of
      delivery included cesarean section (12 cases) and vaginal delivery (3 cases),
      which resulted in 17 newborns, 12 of them with preterm birth (12/17, 70.6 %). The
      gestational age was from 30 weeks + 5 days to 39 weeks. No neonatal malformations
      were found. CONCLUSIONS: The management of malignancies associated with pregnancy
      is a challenge for doctors and patients. It should be based on histological
      subtype, disease stage, gestational age, obstetrics complications, and patient's
      preference regarding continuing the pregnancy.

PMID- 24563260
TI  - Food and beverage advertising during children's television programming.
AB  - BACKGROUND: Increasing prevalence of overweight and obese children in developed
      countries poses a substantial threat to long-term health. One well-described
      factor is the amount of time spent watching television, with exposure to food
      advertising a known influence on food preferences and consumption patterns. AIMS:
      Following recent formulation of new rules regarding advertising of food during
      children's programming, we sought to examine the advertising content in children
      specific television broadcasts on Irish television. METHODS: Advertisement
      content analysis for 5 weekdays of children-specific television broadcasting from
      0700 to 1700 hours on Irish television was performed. Data were coded and
      transferred to SPSS for analyses. Food and beverage advertisements were coded
      based on type of product, nutritional content, intended age group and outcome.
      RESULTS: 322 advertisements were broadcast during the recording period. 31 % (n =
      101) of advertisements related to food or beverage products with 66.3 % (n = 68)
      of food advertisements being for foods that should be eaten in moderation. The
      most frequently recorded food advertisement was for fast food products (27.3 %, n
      = 24), followed by sweets/candy (21.6 %, n = 19) and dairy products (17.0 %, n =
      15). The most frequently recorded beverage advertisement was for natural orange
      juices (46.2 %, n = 6). 54.7 % (n = 176) of advertisements were adult specific
      with 27.3 % (n = 88) being children specific. All food and beverage
      advertisements were associated with a positive outcome (n = 322). CONCLUSIONS:
      These results demonstrate that food and beverages depicted in advertisements
      during children's programming are predominantly unhealthy foods with high salt
      and sugar contents. The findings from this study again highlight the ongoing need
      for new rules regarding food advertising in children's programming.

PMID- 24563262
TI  - Exposure to radiology during medical school.

PMID- 24563261
TI  - Anti-Mullerian hormone normogram in an Irish subfertile population.
AB  - BACKGROUND: There has been much interest in the use of anti-Mullerian hormone
      (AMH) as a biomarker in the assessment of ovarian reserve, and debate on its use
      as a predictor of assisted reproductive technology (ART) outcomes. Normal levels
      have not been well defined, and age-based reference ranges may have a role in
      counselling patients. AIMS: To determine AMH levels in females attending with
      subfertility, identify age-specific centiles and the age-related decline, to
      create population normograms to be used in patient counselling prior to ART.
      METHODS: Retrospective study in a tertiary academic Assisted Conception Centre
      analysing AMH levels in female patients attending for investigation of
      subfertility between January 2009 and December 2011 (n = 3,058). RESULTS: Few
      patients have AMH levels within external laboratory pre-defined "normal fertility
      potential" ranges. Only 8.1 % had "optimal fertility" and 18.6 % "satisfactory",
      with 54.6 % "low" fertility and 15.9 % in the "very low/undetectable" group. By
      age 32, over 50 % of women have AMH levels categorised as "low fertility" (AMH
      <=19.5 pmol/L), increasing to 75 % by age 39. Based on a regression model a
      decrease in mean AMH of 1.72 pmol/L/year was measured. CONCLUSIONS: We recommend
      that each ART centre defines their "own" normograms for accurate advice for and
      treatment of their patients. External laboratory-defined "normal" and "abnormal"
      AMH levels should be filtered and adapted to the reality of each population.
      These findings need to be considered when counselling patients and planning
      treatments as age-specific population normograms can provide a tailored approach.

PMID- 24563263
TI  - Testing systematic genotype by environment interactions using item level data.
AB  - Investigating genotype by environment interactions (GxE) is generally considered
      challenging due to the scale dependency of the interaction effect. The present
      paper illustrates the problems associated with testing for GxEs on summed item
      scores within the well-known ACE model. That is, it is shown how genuine GxEs may
      be masked and how spurious interactions can arise from scaling issues in the
      data. A solution is proposed which explicitly distinguishes between a measurement
      model for the ordinal item responses and a biometric model in which the GxE
      effects are investigated. The new approach is studied in a simulation study using
      both a scenario in which the measurement instrument suffers from mild scaling
      problems and a scenario in which the measurement instrument suffers from severe
      scaling problems. Results indicate that the severity of the scale problems
      affects the power to detect GxE, but it rarely results in false positives. We
      illustrate the new approach on a real dataset concerning affect. 

PMID- 24563264
TI  - Neuregulin 1-induced AKT and ERK phosphorylation in patients with fragile X
      syndrome (FXS) and intellectual disability associated with obstetric
      complications.
AB  - Animal models of fragile X syndrome (FXS) suggest the impairment of the
      intracellular AKT messenger system, which is activated by neuregulin 1 (NRG1), a
      key regulator of neurodevelopment. We investigated NRG1-induced activation of the
      AKT and extracellular signal-regulated kinase (ERK) systems by the measurement of
      the phosphorylated AKT/ERK to total AKT/ERK ratio in peripheral B lymphoblasts of
      patients with FXS, IQ-matched controls with intellectual disability (obstetric
      complications, preterm birth, perinatal hypoxia, and low birth weight), and
      typically developed healthy participants. Results revealed that patients with FXS
      displayed decreased AKT but normal ERK activation after the administration of
      NRG1. IQ-matched controls with intellectual disability displayed intact AKT/ERK
      activation. In conclusion, FXS, but not intellectual disability associated with
      obstetric complications, is associated with decreased NRG1-induced AKT
      phosphorylation.

PMID- 24563270
TI  - Adherence to phosphate binders in hemodialysis patients: prevalence and
      determinants.
AB  - BACKGROUND: Phosphate control is a crucial treatment goal in end-stage renal
      disease, but poor patient adherence to phosphate binder therapy remains a
      challenge. This study aimed to estimate the extent of phosphate binder adherence
      in hemodialysis patients and to identify potential determinants. METHODS:
      Phosphate binder adherence was measured blindly in 135 hemodialysis patients for
      2 months using the medication event monitoring system. Patient data, gathered at
      inclusion through medical records, ad hoc questionnaires and the short form (SF)
      36 health survey, included: (1) demographics, (2) perceived side-effects, belief
      in benefit, self-reported adherence to the therapy, (3) knowledge about phosphate
      binder therapy, (4) social support, and (5) quality of life (SF-36). Phosphatemia
      data was collected from charts. 'Being adherent' was defined as missing <1 total
      daily dose/week and 'being totally adherent' as missing <1 total daily dose/week,
      every week. RESULTS: Mean age of patients was 67 years and 64 % of the sample was
      male. Over the 2 months, 78 % of the prescribed doses were taken. Every week,
      about half of patients were adherent. Over the entire 8-week period, 22 % of
      patients were totally adherent. Mean phosphatemia levels were 0.55 mg/dl lower in
      adherent than nonadherent patients (4.76 vs. 5.31 mg/dl). Determinants for being
      totally adherent were living with a partner, higher social support (both were
      interrelated) and higher physical quality of life. Experiencing intake-related
      inconvenience negatively affected adherence. The social support and quality of
      life physical score explained 26 % of the variance in adherence. CONCLUSIONS:
      Phosphate binder nonadherence remains a major problem. Interventions should aim,
      at least, to improve social support. With few associated factors found and yet
      low adherence, an individualized approach seems indicated.

PMID- 24563271
TI  - Nephrolithiasis by Corynebacterium urealyticum infection: literature review and
      case report.
AB  - INTRODUCTION: Alkaline-encrusted cystitis or pyelonephritis is a chronic
      inflammatory condition due to deposition of crystals usually caused by urea
      splitting bacteria. Corynebacterium urealyticum (CU) is a gram-positive, urea
      splitting and multi-antibiotic resistant bacillus with special tropism for the
      urinary tract and it is often associated with encrusted pyelocystitis. METHODS
      AND RESULTS: Here we report the case of a 75-year-old Caucasian man with a
      prolonged history of renal stones who was admitted for gross hematuria associated
      with renal failure. A diagnosis of encrusted pyelocystitis due to CU infection
      was made and the patient was appropriately treated. CONCLUSIONS: At 6-month
      follow-up the patient was in good general conditions and asymptomatic. Signs of
      urinary tract infection or of renal calculosis were still detectable.

PMID- 24563272
TI  - Classification of degenerative segment disease in adults with deformity of the
      lumbar or thoracolumbar spine.
AB  - BACKGROUND: Lumbar and thoracolumbar deformity in the adult is a condition with
      impairment of health status that can need surgical treatment. In contrast with
      adolescent deformity, where magnitude of the curve plays a significant role in
      surgical indication, the aspects relevant in adult deformity are pain and
      dysfunction that correlate with segment degeneration and imbalance. Previous
      classifications of adult deformity have been of little use for surgical planning.
      METHODS: Chart review and classification of radiographic and clinical findings. A
      classification of degenerative disc disease based on distribution of diseased
      segments and balance status of the spine is presented. RESULTS: Four main
      categories are presented: Type I (limited nonapical segment disease), Type II
      (limited apical segment disease), Type III (extended segment disease--apical and
      nonapical), Type IV (imbalanced spine: IVa, sagittally imbalanced; IVb,
      sagittally and coronally imbalanced). DISCUSSION AND CONCLUSION: Types I and II
      can be treated by fusion of a selective area of the curve. Type III needs fusion
      of all the extension of the coronal curve. Type IV usually needs aggressive
      corrective procedures, frequently including posterior tricolumnar osteotomies.
      This classification permits interpreting the extension and magnitude of the
      disease and can help establish a surgical plan regarding selective fusion and
      methods of sagittal correction. Future research is needed to validate the
      classification.

PMID- 24563273
TI  - Computed tomography-based classification of axis vertebra: choice of screw
      placement.
AB  - PURPOSE: The purpose of the study was to: (1) introduce a new CT-based parameter:
      free facet area and provide its normative data; (2) standardize the method of
      measuring isthmus width and height of the axis vertebra; (3) propose a new
      grading system to predict the difficulty in inserting transarticular and C2
      pedicle screws. METHODS: Spiral CT scans of 47 adult dry axis vertebrae were
      studied. The methods of measuring isthmus width, isthmus height and free facet
      area are described. RESULTS: The mean isthmus width was 5.04 mm on the right side
      and 5.42 mm on the left side. The mean isthmus height was 5.21 mm on the right
      side and 5.45 mm on the left side. Mean free facet area was 61.23 % on the right
      side and 70.18 % on the left side. A novel grading system is proposed on the
      basis of these three parameters. As per this grading system, 40.4 % of the sides
      were found to be difficult for transarticular and 24.5 % sides for C2 pedicle
      screw insertion (total score 2, 3, 4). A Management protocol is suggested on the
      basis of the grading system. CONCLUSION: Inserting a transarticular screw was
      more frequently difficult as compared to pedicle screw. A new CT-based parameter
      (free facet area) and an efficient grading have been proposed to help surgeons
      choose the appropriate screw options, appreciate the complex anatomy of this
      region and compare data across various studies.

PMID- 24563275
TI  - Accurate determination of the pathological stage with gross dissection protocol
      for radical cystectomy.
AB  - The current protocol for reporting urinary bladder cancer in radical cystectomies
      may exhibit limitations in the diagnostic accuracy, such as a risk of
      understaging, especially in cases with prostatic involvement. Difficulty can
      arise in the verification of stage pT0, and the assessment of surgical margins is
      suboptimal. We have developed a daily gross dissection protocol practice where
      radical cystectomies are totally embedded and evaluated histologically in whole
      mount sections. We report here on the first 138 consecutive specimens from 2008
      to the first quarter of 2012 inclusive. The incidence of the cancer stages was
      compared with data on 15,586 radical cystectomies from the literature. The
      differences were analyzed with the one-sample z-test (p < 0.05). The following
      emerged from and our series and the literature data: pT0 8.7 % and 6.1 %; pTa 0.7
      % and 2.9 %; pTis 2.9 % and 6 %; pT1 15.2 % and 15.5 %; pT2 21 % and 23.3 %; pT3
      34.8 % and 34.3 %; and pT4 16.7 % and 11 %, respectively. Our findings closely
      reflected the means of the published statistical data based on a large number of
      cases. The differences were due to the more detailed processing: the case numbers
      in groups from pTis to pT2 were comparatively low, while those in groups pT3 and
      pT4 were higher. The difference in group pT4 was significant (p = 0.0494). With
      this method, only those samples were regarded as pT0 in which the granulomatous
      area and the hemosiderin deposition indicative of the earlier intervention were
      observable and the entire preparation was tumor-free.

PMID- 24563276
TI  - Multichannel intraluminal impedance-pH testing is clinically useful in the
      management of patients with gastroesophageal reflux symptoms.
AB  - BACKGROUND: Multichannel intraluminal impedance-pH testing (MII-pH) allows for
      the detection of acid and non-acid reflux, thus, increasing yield over pH
      testing. Limited data exist on how physicians use test results in practice. AIM:
      The aim of our study was to evaluate the influence of MII-pH testing on patient
      care. METHODS: We reviewed records of patients with symptoms of gastroesophageal
      reflux disease who underwent MII-pH testing. Management decisions evaluated
      included changes in prescribed medications and surgical consultation for anti
      reflux surgery. Statistical analysis was performed using Pearson Chi square test,
      and multivariable logistic regression. RESULTS: MII-pH testing resulted in a
      medication change in 41% of patients, surgical consultation in 19.7%, and anti
      reflux surgery in 11.1%. In patients who were not on proton pump inhibitor (PPI)
      therapy, MII-pH results were most useful in the decision to start a PPI. On PPI
      therapy, results were more often used to decide whether to increase (32.3%) or
      switch the PPI (23.5%) in patients with continued acid reflux. Results were most
      useful to stop the PPI in normal studies (11.1%). More patients with non-acid
      reflux (14.3%) and normal results (19.7%) were started on a neuromodulator
      compared to other diagnoses. The MII-pH result was most useful in the decision to
      start baclofen or bethanecol when the patient was found to have non-acid reflux
      (25%). Patients with an abnormal MII-pH or abnormal MII alone were more likely to
      be referred to surgery (OR 19.5, p < 0.001; OR 19.77, p < 0.001). CONCLUSIONS:
      MII-pH testing impacted medical or surgical management in over half the patients
      tested.

PMID- 24563274
TI  - Pneumococcal empyema and complicated pneumonias: global trends in incidence,
      prevalence, and serotype epidemiology.
AB  - This review evaluates the serotype epidemiology of complicated pneumococcal
      pneumonia (CPP) during the period 1990-2012. PubMed and EMBASE were searched
      using the terms "empyema", "complicated pneumonia", "pleural infection",
      "necrotizing pneumonia", "pleural effusion", "parapneumonic effusion",
      "pneumatocele", or "lung abscess"; "pneumococcal" or "Streptococcus pneumoniae";
      and "serotype" for studies on the epidemiology of complicated pneumonias
      published from January 1, 1990 to October 1, 2013. Studies with data on incidence
      and serotypes were included; reviews, case reports, and conference abstracts were
      excluded. Of 152 papers, 84 fitted the inclusion criteria. A few pneumococcal
      serotypes were predominant causes of CPP, particularly serotypes 1, 19A, 3, 14,
      and 7F. CPP was a more common manifestation of pneumococcal disease among older
      (>2 years old) than younger children. The data support increases in both reported
      incidence rates and proportions of CPP in children and adults during the period
      1990-2012; specific increases varied by geographic region. The proportions of
      serotype 3 and, particularly in Asia, serotype 19A CPP have increased, whereas
      most studies show declines in serotype 14. Serotype 1 has been a predominant
      cause of CPP since 1990, while antibiotic resistance was infrequent among
      serotype 1 isolates. The reported incidence and proportions of CPP among
      pneumonia cases steadily increased from 1990 to 2012. Several factors might
      account for these increases, including enhanced disease detection due to a higher
      index of suspicion, more sophisticated diagnostic assays, and changes in the
      prevalence of serotypes with capacity to invade the pleural space that were not
      targeted by the 7-valent pneumococcal conjugate vaccine (PCV7). 

PMID- 24563277
TI  - Association of single nucleotide polymorphisms of nucleotide excision repair
      genes with laryngeal cancer risk and interaction with cigarette smoking and
      alcohol drinking.
AB  - We investigated the potential association of 12 single nucleotide polymorphisms
      (SNPs) of nucleotide excision repair (NER) genes with risk of laryngeal cancer. A
      ratio of 1:1 matched case-control study was conducted. Conditional regression
      analysis indicated that subjects with ERCC1 rs11615 CC and C allele had an
      increased risk of laryngeal cancer compared with the TT genotype. Individuals
      with the ERCC5 rs17655 GG and G allele had a moderately increased risk of
      laryngeal cancer when compared with the CC genotype. By stratified analysis,
      ERCC1 rs11615 CC genotype and C allele were significantly associated with greatly
      increased risk of laryngeal cancer in ever smokers. ERCC1 rs11615 and ERCC5
      rs17655 polymorphisms were associated with a moderately increased risk of this
      cancer in ever drinkers. In summary, we suggest that genetic variations in ERCC1
      rs11615 and ERCC5 rs17655 are associated with laryngeal cancer risk in a Chinese
      population, especially in ever smokers and drinkers. Our finding could be helpful
      in identifying people at high risk for the disease for early intervention. 

PMID- 24563278
TI  - Prognostic role of circulating tumor cells and disseminated tumor cells in
      patients with prostate cancer: a systematic review and meta-analysis.
AB  - Circulating tumor cells (CTCs) and disseminated tumor cells (DTCs) displayed
      their roles in prognosis prediction in prostate cancer. The objective of the
      present study was to conduct a systematic review and meta-analysis of published
      literature while investigating the correlation between survival outcome and CTCs
      or DTCs counts in patients with prostate cancer. Relevant literature was searched
      in Pubmed and Embase. Survival data of included study were extracted. Forrest
      plots were used to estimate the effect of CTCs/DTCs on the survival of patients.
      Publication bias was evaluated using Begg's test. The estimated HRs and 95 %
      confidence interval for the effect of CTCs/DTCs on overall survival (OS) and
      biochemical relapse-free survival (bRFS) or disease-free survival (DFS) were 2.43
      [2.07, 2.86] (p<0.00001) and 2.15 [1.69, 2.73] (p<0.00001), respectively.
      Subgroup analysis revealed that CTCs were also relevant to poor prognosis (hazard
      ratio (HR) 2.43 [2.05, 2.89] for OS, HR 2.46 [2.08, 2.90] for bRFS/DFS). A
      similar result was yielded in DTCs (1.47 [1.21, 1.80] for DFS). CTCs/DTCs could
      also predict poor OS in metastatic prostate cancer (2.37 [1.99, 2.82], p<0.00001)
      and in localized stage (HR 1.84 [1.47, 2.28], p<0.00001). In addition, CTCs/DTCs
      detected by different methods, especially by CellSearch system (HR for OS 2.36
      [1.95, 2.85] and HR for bRFS/DFS 2.53 [1.66, 3.85]), were relevant to poor
      prognosis. Available evidence supported the notion of the strong prognostic value
      of CTCs. CTCs are promising biomarkers that are clinically implemented in the
      therapeutic decision-making process in patients with prostate cancer.

PMID- 24563279
TI  - Matrix metalloproteinase-13 expression in the progression of colorectal adenoma
      to carcinoma : Matrix metalloproteinase-13 expression in the colorectal adenoma
      and carcinoma.
AB  - Most colorectal carcinomas (CRCs) are considered to arise from conventional
      adenoma based on the concept of the adenoma-carcinoma sequence. Matrix
      metalloproteinases (MMPs) are known to be overexpressed as normal mucosa
      progresses to adenomas and carcinomas. There has been little previous
      investigation about MMP-13 expression in adenoma-carcinoma sequence. In this
      study, we aimed to investigate the immunohistochemical expression of MMP-13 in
      colorectal adenoma and CRC specimens using tissue microarray (TMA) technique. A
      total of 40 cases of CRC associated with adenoma were collected from files of the
      Pathology laboratory at Mansoura Gastroenterology Center between January 2007 and
      January 2012. Sections from TMA blocks were prepared and stained for MMP-13.
      Immunoreactivity to MMP-13 staining was localized to the cytoplasm of mildly,
      moderately, and severely dysplatic cells of adenomas and CRC tumor cells that
      were either homogenous or heterogeneous. There was no significant difference in
      MMP-13 expression between adenomas and CRCs either non-mucinous or mucinous.
      Adenomas with high MMP-13 expression were significantly associated with moderate
      to marked degree of inflammatory cellular infiltrate and presence of familial
      adenomatous polyps. In conclusion, MMP-13 may be a potential biological marker of
      early tumorigenesis in the adenoma-carcinoma sequence. 

PMID- 24563280
TI  - The association of Crk-like adapter protein with poor prognosis in glioma
      patients.
AB  - Glioma is the most common of brain tumors that greatly affects patient survival.
      In our precious study, Crk-like adapter protein (CrkL) was identified as a key
      regulator in glioblastoma development [1]. Here, we aimed to investigate the
      correlation of CrkL with patient prognosis as well as pathological indicators.
      Immunohistochemistry was available to evaluate CrkL expression in 49 gliomas of
      distinct malignancy grade, and positive stained sites were analyzed. CrkL protein
      was detected in cell lines by Western blot as well. We observed CrkL protein
      stained in 59.2 % (29 out of 49) of all glioma tissues, including 41.4 % of low
      grade (I + II) gliomas, and 85.0 % of high-grade (III + IV) gliomas. Of four
      grades, grade IV exhibited the highest CrkL level. CrkL protein was also
      identified in cell lines NHA, U87, U251, T98G, and A172 by Western blot. On the
      other hand, CrkL expression was significantly associated with the patient's age
      and WHO grade, and patients with high CrkL expression had a significantly shorter
      median survival time (17 months) than those (median survival time 52 months) with
      low CrkL expression (p<0.001). According to Cox regression, CrkL can be suggested
      as an independent prognostic factor. In conclusion, CrkL is differently expressed
      in different grades of gliomas, and correlated to WHO grade. CrkL also
      independently indicates poor prognosis in old glioma patients, which can further
      be recommended as an effective prognostic biomarker or therapeutic target.

PMID- 24563281
TI  - A plastid without a genome: evidence from the nonphotosynthetic green algal genus
      Polytomella.
AB  - Polytomella spp. are free-living, nonphotosynthetic green algae closely related
      to the model organism Chlamydomonas reinhardtii. Although colorless, Polytomella
      spp. have a plastid, but it is still unknown whether they harbor a plastid
      genome. We took a next generation sequencing approach, along with transcriptome
      sequencing, to search for a plastid genome and an associated gene expression
      system in Polytomella spp. Illumina sequencing of total DNA from four Polytomella
      spp. did not produce any recognizable plastid-derived reads but did generate a
      large number of mitochondrial DNA sequences. Transcriptomic analysis of
      Polytomella parva uncovered hundreds of putative nuclear-encoded, plastid
      targeted proteins, which support the presence of plastid-based metabolic
      functions, similar to those observed in the plastids of other nonphotosynthetic
      algae. Conspicuously absent, however, were any plastid-targeted proteins involved
      in the expression, replication, or repair of plastid DNA. Based on these findings
      and earlier findings, we argue that the Polytomella genus represents the first
      well-supported example, to our knowledge, of a primary plastid-bearing lineage
      without a plastid genome. 

PMID- 24563283
TI  - Perennial roots to immortality.
AB  - Maximum lifespan greatly varies among species, and it is not strictly determined;
      it can change with species evolution. Clonal growth is a major factor governing
      maximum lifespan. In the plant kingdom, the maximum lifespans described for
      clonal and nonclonal plants vary by an order of magnitude, with 43,600 and 5,062
      years for Lomatia tasmanica and Pinus longaeva, respectively. Nonclonal perennial
      plants (those plants exclusively using sexual reproduction) also present a huge
      diversity in maximum lifespans (from a few to thousands of years) and even more
      interestingly, contrasting differences in aging patterns. Some plants show a
      clear physiological deterioration with aging, whereas others do not. Indeed, some
      plants can even improve their physiological performance as they age (a phenomenon
      called negative senescence). This diversity in aging patterns responds to species
      specific life history traits and mechanisms evolved by each species to adapt to
      its habitat. Particularities of roots in perennial plants, such as meristem
      indeterminacy, modular growth, stress resistance, and patterns of senescence, are
      crucial in establishing perenniality and understanding adaptation of perennial
      plants to their habitats. Here, the key role of roots for perennial plant
      longevity will be discussed, taking into account current knowledge and
      highlighting additional aspects that still require investigation. 

PMID- 24563282
TI  - Genome structures and transcriptomes signify niche adaptation for the multiple
      ion-tolerant extremophyte Schrenkiella parvula.
AB  - Schrenkiella parvula (formerly Thellungiella parvula), a close relative of
      Arabidopsis (Arabidopsis thaliana) and Brassica crop species, thrives on the
      shores of Lake Tuz, Turkey, where soils accumulate high concentrations of
      multiple-ion salts. Despite the stark differences in adaptations to extreme salt
      stresses, the genomes of S. parvula and Arabidopsis show extensive synteny. S.
      parvula completes its life cycle in the presence of Na+, K+, Mg2+, Li+, and
      borate at soil concentrations lethal to Arabidopsis. Genome structural
      variations, including tandem duplications and translocations of genes, interrupt
      the colinearity observed throughout the S. parvula and Arabidopsis genomes.
      Structural variations distinguish homologous gene pairs characterized by
      divergent promoter sequences and basal-level expression strengths. Comparative
      RNA sequencing reveals the enrichment of ion-transport functions among genes with
      higher expression in S. parvula, while pathogen defense-related genes show higher
      expression in Arabidopsis. Key stress-related ion transporter genes in S. parvula
      showed increased copy number, higher transcript dosage, and evidence for
      subfunctionalization. This extremophyte offers a framework to identify the
      requisite adjustments of genomic architecture and expression control for a set of
      genes found in most plants in a way to support distinct niche adaptation and
      lifestyles.

PMID- 24563285
TI  - Identification of microRNA-18a as a novel regulator of the insulin-like growth
      factor-1 in the proliferation and regeneration of deer antler.
AB  - To investigate the effect of miR-18a on the regulation of the insulin-like growth
      factor (IGF-1) during growth of antlers in sika deer, miRNA Chip analysis, Target
      Scan and real-time PCR analysis were used to identify miRNAs that bind to the 3'
      UTR of IGF-1. An miR-18a mimic was transfected into antler cartilage cells and
      the expression levels were quantified by real-time PCR. Dual luciferase assays
      revealed that miR-18a binds to the 3'-UTR of the IGF-1 gene thus indicating this
      to be a target gene regulated by miR-18a. MTT assays and cell-cycle analyses
      confirmed that miR-18a significantly inhibited proliferation of cartilage cells.
      In contrast, transfection of miR-18a inhibitors increased proliferation.
      Furthermore, Western blot analysis showed that over-expression of miR-18a down
      regulated IGF-1 protein levels while IGF-1 expression was increased after
      transfection of miR-18a inhibitors. Thus, miR-1 down-regulated IGF-1 expression
      thus implicating miR-18a as an important regulator of antler proliferation. 

PMID- 24563286
TI  - Homology modeling and function of trehalose synthase from Pseudomonas putida P06.
AB  - Trehalose is a non-reducing disaccharide that has wide applications in the food
      industry and pharmaceutical manufacturing. Trehalose synthase (TreS) from
      Pseudomonas putida P06 catalyzes the reversible interconversion of maltose and
      trehalose and may have applications in the food industry. However, the catalytic
      mechanism of TreS is not well understood. Here, we investigated the structural
      characteristics of this enzyme by homology modeling. The highly conserved Asp294
      residue was identified to be critical for catalytic activity. In addition,
      flexible docking studies of the enzyme-substrate system were performed to predict
      the interactions between TreS and its substrate, maltose. Amino acids that
      interact extensively with the substrate and stabilize the substrate in an
      orientation suitable for enzyme catalysis were identified. The importance of
      these residues for catalytic activity was confirmed by the biochemical
      characterization of the relevant mutants generated by site-directed mutagenesis. 

PMID- 24563287
TI  - Chimeric repressor analysis identifies MYB87 as a possible regulator of
      morphogenesis via cell wall organization and remodeling in Arabidopsis.
AB  - Plant growth and development require proper cell wall organization but little is
      known about the transcription factors responsible for the regulation of gene
      expression involved in cell wall organization. Here we show, using Arabidopsis
      thaliana, that constitutive expression of the chimeric repressor for the MYB87
      transcription factor causes suppression of longitudinal elongation, aberrant
      radial growth, and radially expanded or swollen cells in multiple organs.
      Microarray analysis revealed that plants expressing the chimeric repressor have
      altered expression of various cell wall related genes. MYB87 may therefore
      function as a regulator of genes affecting cell wall organization and remodeling.
      These findings improve our understanding of cell wall regulation and its roles in
      plant growth and development and also contribute information that may allow
      engineering of plant growth and architecture. 

PMID- 24563284
TI  - Recombinant allergens for diagnosis of cockroach allergy.
AB  - Molecular cloning of cockroach allergens and their expression as recombinant
      proteins have allowed a better understanding of the mechanisms of cockroach
      allergic disease. Recombinant cockroach allergens have been used for skin testing
      or in vitro methods to measure IgE antibody levels in serum. Early studies
      evaluating selected U.S. patients revealed that a cocktail of four cockroach
      allergens, Bla g 1, Bla g 2, Bla g 4, and Bla g 5, would identify 95 % of
      cockroach allergic patients. More recent studies pointed to an important role of
      sensitization to tropomyosin among certain populations, and suggested that a
      cocktail of five allergens Bla g 1 and/or Per a 1, Bla g 2, Bla g 4, Bla g 5, and
      Bla g 7, and/or Per a 7, would be expected to diagnose 50- 64 % of cockroach
      allergic patients worldwide. Variation in IgE reactivity profiles could be in
      part due to IgE responses to cross-reactive homologous allergens from different
      origins. The availability of purified natural or recombinant cockroach allergens
      provides the capacity to improve diagnosis of cockroach allergy and to develop
      novel forms of immunotherapy for cockroach-allergic patients. 

PMID- 24563288
TI  - An optical multi-sensing system for detection of cardiovascular toxicity.
AB  - A mini-microscope-based system for multisite detection of cardiovascular toxicity
      was developed. The mini-microscope consisted of an image sensor and lens module
      extracted from an inexpensive webcam. The flipped lens module enabled cells to be
      magnified and monitored during testing. The portability and compactness of this
      system enables short-term and potential long-term experimentation inside a
      conventional incubator. The toxicity test results demonstrated that the
      normalized beating rates of cardiac muscle cells selected from multiple regions
      increased over time when treated with 100 nM isoprenaline. The presented system
      could be a promising cost-effective cell-based testing tool for discovering and
      screening drugs.

PMID- 24563289
TI  - Galactosylated collagen matrix enhanced in vitro maturation of human embryonic
      stem cell-derived hepatocyte-like cells.
AB  - Due to their important biomedical applications, functional human embryonic stem
      cell-derived hepatocyte-like cells (hESC-HLCs) are an attractive topic in the
      field of stem cell differentiation. Here, we have initially differentiated hESCs
      into functional hepatic endoderm (HE) and continued the differentiation by
      replating them onto galactosylated collagen (GC) and collagen matrices. The
      differentiation of hESC-HE cells into HLCs on GC substrate showed significant up
      regulation of hepatic-specific genes such as ALB, HNF4alpha, CYP3A4, G6P, and
      ASGR1. There was more albumin secretion and urea synthesis, as well as more
      cytochrome p450 activity, in differentiated HLCs on GC compared to the collagen
      coated substrate. These results suggested that GC substrate has the potential to
      be used for in vitro maturation of hESC-HLCs. 

PMID- 24563290
TI  - Diverse expression levels of two codon-optimized genes that encode human
      papilloma virus type 16 major protein L1 in Hansenula polymorpha.
AB  - Two versions of an optimized gene that encodes human papilloma virus type 16
      major protein L1 were designed according to the codon usage frequency of Pichia
      pastoris. Y16 was highly expressed in both P. pastoris and Hansenula polymorpha.
      M16 expression was as efficient as that of Y16 in P. pastoris, but merely
      detectable in H. polymorpha even though transcription levels of M16 and Y16 were
      similar. H. polymorpha had a unique codon usage frequency that contains many more
      rare codons than Saccharomyces cerevisiae or P. pastoris. These findings indicate
      that even codon-optimized genes that are expressed well in S. cerevisiae and P.
      pastoris may be inefficiently expressed in H. polymorpha; thus rare codons must
      be avoided when universal optimized gene versions are designed to facilitate
      expression in a variety of yeast expression systems, especially H. polymorpha is
      involved. 

PMID- 24563291
TI  - Purification and evaluation of the enzymatic properties of a novel
      fructosyltransferase from Aspergillus oryzae: a potential biocatalyst for the
      synthesis of sucrose 6-acetate.
AB  - A novel fructosyltransferase (AoFT) capable of synthesizing sucrose 6-acetate
      (S6A) from sucrose and glucose 6-acetate has been purified to homogeneity from
      Aspergillus oryzae ZZ-01. Its molecular mass was ~50 kDa by SDS-PAGE; optimal
      activity was at 45  degrees C and it was stable from pH 4.5 to 7.5 with an
      optimum pH of 6. Mg(2+), K(+) (5 mM), propanol, toluene (50%, v/v), Tween 20 or
      Triton X-100 (1%, w/v) increased the transfructosylation activity by 20, 17, 17,
      10, 25 and 20%, respectively. An overall conversion of 32% was achieved under
      optimal conditions over 24 h. This is the first report that the purified and
      characterized the fructosyltransferase from Aspergillus capable of synthesis of
      S6A from sucrose and glucose 6-acetate.

PMID- 24563292
TI  - Recent developments in use of 1-aminocyclopropane-1-carboxylate (ACC) deaminase
      for conferring tolerance to biotic and abiotic stress.
AB  - Ethylene is an essential plant hormone also known as a stress hormone because its
      synthesis is accelerated by induction of a variety of biotic and abiotic stress.
      The plant growth promoting bacteria containing the enzyme 1-aminocyclopropane-1
      carboxylate (ACC) deaminase enhances plant growth by decreasing plant ethylene
      levels under stress conditions. The expression of ACC deaminase (acdS) gene in
      transgenic plants is an alternative approach to overcome the ethylene-induced
      stress. Several transgenic plants have been engineered to express both
      bacterial/plant acdS genes which then lowers the stress-induced ethylene levels,
      thus efficiently combating the deleterious effects of environmental stresses.
      This review summarizes the current knowledge of various transgenic plants
      overexpressing microbial and plant acdS genes and their potential under diverse
      biotic and abiotic stresses. Transcription regulation mechanism of acdS gene from
      different bacteria, with special emphasis to nitrogen fixing bacteria is also
      discussed in this review. 

PMID- 24563293
TI  - Phloem-specific expression of the lectin gene from Allium sativum confers
      resistance to the sap-sucker Nilaparvata lugens.
AB  - Rice production is severely hampered by insect pests. Garlic lectin gene (ASAL)
      holds great promise in conferring protection against chewing (lepidopteran) and
      sap-sucking (homopteran) insect pests. We have developed transgenic rice lines
      resistant to sap-sucking brown hopper (Nilaparvata lugens) by ectopic expression
      of ASAL in their phloem tissues. Molecular analyses of T0 lines confirmed stable
      integration of transgene. T1 lines (NP 1-2, 4-3, 11-6 & 17-7) showed active
      transcription and translation of ASAL transgene. ELISA revealed ASAL expression
      was as high as 0.95% of total soluble protein. Insect bioassays on T2 homozygous
      lines (NP 18 & 32) revealed significant reduction (~74-83%) in survival rate,
      development and fecundity of brown hoppers in comparison to wild type.
      Transgenics exhibited enhanced resistance (1-2 score) against brown hoppers,
      minimal plant damage and no growth penalty or phenotypic abnormalities.

PMID- 24563294
TI  - Enhanced encapsulation of chondrocytes within a chitosan/hyaluronic acid
      hydrogel: a new technique.
AB  - Two encapsulation techniques for rabbit chondrocytes in chitosan/hyaluronic acid
      gel have been compared. The standard technique involves the cross-linking of
      chitosan and hyaluronic acid at 2:1 (w/w). In the modified technique, cells were
      initially added to 33% of hyaluronic acid dialdehyde and the gelation process was
      completed with the remaining 67%. This minimised the cell loss and improved the
      encapsulation of the cells. By the third week, the modified technique showed
      better seeding density, with matrix synthesis (per scaffold) of 11 MUg as
      compared to 1.1 MUg in the current technique. Relative expression of collagen II
      with the current technique and the modified technique were 6.4% and ~1,600%
      respectively. The modified technique was superior for matrix synthesis and
      maintenance of phenotype.

PMID- 24563295
TI  - Fungal elicitor protein PebC1 from Botrytis cinerea improves disease resistance
      in Arabidopsis thaliana.
AB  - We previously identified a novel protein elicitor, PebC1, from Botrytis cinerea
      and described its enhancement of plant growth, drought tolerance and disease
      resistance in tomato. Here, we have investigated the defense-associated molecular
      responses in Arabidopsis thaliana after treatment with recombinant PebC1. PebC1
      was expressed in Escherichia coli. Recombinant protein treatments improved plant
      resistance to Botrytis infection and maintained plant defenses for more than 21
      days. The purified protein at 10 MUg ml(-1) activated extracellular medium
      alkalization (pH) and reactive oxygen species and nitric oxide generation and
      also induced defense gene expression. Arabidopsis mutants that are insensitive to
      salicylic acid had increased resistance to Botrytis infection after PebC1
      treatment but PebC1 did not affect the resistance of mutants with jasmonic acid
      and ethylene transduction pathways. The results suggest that PebC1 can function
      as an activator of plant disease resistance and can promote disease resistance to
      Botrytis in A. thaliana through the ethylene signal transduction pathway.

PMID- 24563296
TI  - scFv antibodies against infectious bursal disease virus isolated from a
      combinatorial antibody library by flow cytometry.
AB  - Infectious bursal disease is an economically important disease that affects
      chickens worldwide. Here, a recombinant single chain variable fragment (scFv)
      antibody library derived from chickens immunized with VP2 protein of infectious
      bursal disease virus (IBDV) was constructed. The library was subjected to three
      rounds of screening by flow cytometry against VP2 protein through a bacteria
      display technology, resulting in the enrichment of scFv. Three scFv clones with
      different fluorescence intensity were obtained by random colony pick up. The
      isolated scFv antibodies were expressed and purified. Relative affinity assay
      showed the three clones had different sensitivity to VP2, in accordance with
      fluorescence activity cell sorting analysis. The potential use of the selected
      IBDV-specific scFv antibodies was demonstrated by the successful application of
      the isolated antibodies in western blotting assay and ELISA. 

PMID- 24563297
TI  - Acute mechanical overload increases IGF-I and MMP-9 mRNA in 3D tissue-engineered
      skeletal muscle.
AB  - Skeletal muscle (SkM) is a tissue that responds to mechanical load following both
      physiological (exercise) or pathophysiological (bed rest) conditions. The
      heterogeneity of human samples and the experimental and ethical limitations of
      animal studies provide a rationale for the study of SkM plasticity in vitro. Many
      current in vitro approaches of mechanical loading of SkM disregard the three
      dimensional (3D) structure in vivo. Tissue engineered 3D SkM, that displays
      highly aligned and differentiated myotubes, was used to investigate mechano
      regulated gene transcription of genes implicated in hypertrophy/atrophy. Static
      loading (STL) and ramp loading (RPL) at 10 % strain for 60 min were used as
      mechano-stimulation with constructs sampled immediately for RNA extraction. STL
      increased IGF-I mRNA compared to both RPL and CON (control, p = 0.003 and 0.011
      respectively) whilst MMP-9 mRNA increased in STL and RPL compared to CON (both p
      < 0.05). IGFBP-2 mRNA was differentially regulated in RPL and STL compared to CON
      (p = 0.057), whilst a reduction in IGFBP-5 mRNA was found for STL and RPL
      compared to CON (both p < 0.05). There was no effect in the expression of
      putative atrophic genes, myostatin, MuRF-1 and MAFBx (all p > 0.05). These data
      demonstrate a transcriptional signature associated with SkM hypertrophy within a
      tissue-engineered model that more greatly recapitulates the in vivo SkM structure
      compared previously published studies.

PMID- 24563298
TI  - Copper-containing mesoporous bioactive glass coatings on orbital implants for
      improving drug delivery capacity and antibacterial activity.
AB  - Anophthalmic orbit restoration with artificial implants is usually accompanied
      with the risks of bacterial penetration and implant exposure. Here, we develop a
      facile evaporation-inducing self-assembly approach to modify the porous
      hydroxyapatite (pHA) orbital implants by using sol-gel derived CuO-containing
      mesoporous bioactive glass (Cu-MBG). The Cu-MBG coatings with 0-5 mol% CuO were
      prepared in the pore wall of pHA by immersion-evaporation-ageing route in the sol
      precursor of Cu-MBG. Brunauer-Emmett-Teller and Barrette-Joyner-Halenda analyses
      showed that the specific surface area and pore volume were slightly decreased
      with increasing CuO content, while the Cu-MBG-modified pHA maintained a sustained
      release of ofloxacin and significantly inhibited the bacterial viability
      (Staphylococcus aureus and Escherichia coli). These studies demonstrate that the
      Cu-MBG modification provides an effective and facile strategy to endow combined
      biological performances of pHA orbital implants and potentially reduce implant
      related side effects.

PMID- 24563299
TI  - Removing environmental organic pollutants with bioremediation and
      phytoremediation.
AB  - Hazardous organic pollutants represent a threat to human, animal, and
      environmental health. If left unmanaged, these pollutants could cause concern.
      Many researchers have stepped up efforts to find more sustainable and cost
      effective alternatives to using hazardous chemicals and treatments to remove
      existing harmful pollutants. Environmental biotechnology, such as bioremediation
      and phytoremediation, is a promising field that utilizes natural resources
      including microbes and plants to eliminate toxic organic contaminants. This
      technology offers an attractive alternative to other conventional remediation
      processes because of its relatively low cost and environmentally-friendly method.
      This review discusses current biological technologies for the removal of organic
      contaminants, including chlorinated hydrocarbons, focusing on their limitation
      and recent efforts to correct the drawbacks. 

PMID- 24563300
TI  - Pluripotent-related gene expression analyses in single porcine recloned embryo.
AB  - The developmental ability among embryos produced by three different techniques
      were examined: there were no significant differences in the developmental rate in
      porcine embryos produced by in vitro fertilization (IVF) and first generation of
      somatic cell nucleus transfer (SCNT), but the developmental rate dropped sharply
      at the 2- to four-cell stage in recloned (second generation of SCNT) embryos. In
      most recloned embryos, Oct4 and Klf4 were under-expressed at all stages, whereas
      Sox2 and Nanog were over-expressed at the two-cell stage. In contrast, Nanog was
      absent in IVF and SCNT embryos at the two-cell stage. The recloned embryos were
      treated with valproic acid to enhance developmental capacity and this led to an
      increase in the rate of blastocyst formation and total cell number compared with
      the findings for untreated recloned embryos (29.8 vs. 12.4 %, 39 vs. 25,
      respectively, p < 0.05). 

PMID- 24563301
TI  - Inhibition of autophagy by autophagic inhibitors enhances apoptosis induced by
      bortezomib in non-small cell lung cancer cells.
AB  - Bortezomib is a novel proteasome inhibitor that has promising antitumor activity
      against various cancer cells. We have assessed its antitumor activity in non
      small cell lung cancer (NSCLC) A549 and H157 cells in vitro where it inhibited
      cell growth and induced apoptosis, which was associated with cytochrome c release
      and caspase-3 activation. Bortezomib upregulated autophagic-related proteins, the
      Atg12-Atg5 complex and LC3-II, which indicated autophagy had occurred. The
      combination of bortezomib with autophagic inhibitor 3-methyladenine or
      chloroquine significantly enhanced suppression of cell growth and apoptosis
      induced by bortezomib in A549 and H157 cells. Our study indicated that inhibition
      of both proteasome and autophagy has great potential for NSCLC treatment. 

PMID- 24563302
TI  - Improving bgl1 gene expression in Saccharomyces cerevisiae through meiosis in an
      isogenic triploid.
AB  - Introducing large numbers of target genes into the chromosome of Saccharomyces
      cerevisiae via delta-sequence-mediated integration is a good strategy for
      exploring the effects of gene dosage on expression and secretion of heterologous
      proteins. The expression of exogenous genes might be further improved through
      meiosis in an isogenic triploid. Here, a stable strain A-8 was screened from 35
      sexual spore colonies obtained from an isogenic triploid integratively expressing
      bgl1 from Aspergillus aculeatus. The corresponding beta-glucosidase activity in
      this strain was increased by ~120 % compared with the parent strain BGL-a.
      Measurement of doubling time, flow cytometry, and mating experiments further
      confirmed that A-8 was a spore-forming strain obtained from a triploid parent.
      Thus, combining delta-integration and meiosis in an isogenic triploid is a
      promising approach for improving the expression of exogenous proteins in S.
      cerevisiae. 

PMID- 24563303
TI  - Highly selective hydrolysis for the outer glucose at the C-20 position in
      ginsenosides by beta-glucosidase from Thermus thermophilus and its application to
      the production of ginsenoside F2 from gypenoside XVII.
AB  - beta-Glucosidase from Thermus thermophilus has specific hydrolytic activity for
      the outer glucose at the C-20 position in protopanaxadiol-type ginsenosides
      without hydrolysis of the inner glucose. The hydrolytic activity of the enzyme
      for gypenoside XVII was optimal at pH 6.5 and 90  degrees C, with a half-life of
      1 h with 3 g enzyme l(-1) and 4 g gypenoside XVII l(-1). Under the optimized
      conditions, the enzyme converted the substrate gypenoside XVII to ginsenoside F2
      with a molar yield of 100 % and a productivity of 4 g l(-1) h(-1). The conversion
      yield and productivity of ginsenoside F2 are the highest reported thus far among
      enzymatic transformations. 

PMID- 24563305
TI  - Matrix metalloproteinases are important for follicular development in normal and
      miniature pigs.
AB  - To determine the differences in the follicular development process of normal and
      miniature pigs, we compared the expression of matrix metalloproteinases (MMP) in
      these two breeds throughout folliculogenesis. In normal pigs, MMP-9 was highly
      expressed in all stages of the follicular development as well as during
      ovulation. The follicular development exhibited strong gelatinase activity. The
      expression of MMP-2 remained insignificant throughout folliculogenesis in both
      breeds. However, for the follicles of miniature pigs, MMP-2 level was higher than
      that in normal pigs. Thus MMP types may regulate the remodelling of follicular
      tissue in the ovaries of normal and miniature pigs. The differential expression
      of MMPs observed in this study reflected the mechanisms underlying ovarian
      follicular development in these two breeds. 

PMID- 24563304
TI  - Generation of a cre recombinase-conditional Nos1ap over-expression transgenic
      mouse.
AB  - Polymorphic non-coding variants at the NOS1AP locus have been associated with the
      common cardiac, metabolic and neurological traits and diseases. Although, in
      vitro gene targeting-based cellular and biochemical studies have shed some light
      on NOS1AP function in cardiac and neuronal tissue, to enhance our understanding
      of NOS1AP function in mammalian physiology and disease, we report the generation
      of cre recombinase-conditional Nos1ap over-expression transgenic mice (Nos1ap
      (Tg)). Conditional transgenic mice were generated by the pronuclear injection
      method and three independent, single-site, multiple copies integration event
      based founder lines were selected. For heart-restricted over-expression, Nos1ap
      (Tg) mice were crossed with Mlc2v-cre and Nos1ap transcript over-expression was
      observed in left ventricles from Nos1ap (Tg); Mlc2v-cre F1 mice. We believe that
      with the potential of conditional over-expression, Nos1ap (Tg) mice will be a
      useful resource in studying NOS1AP function in various tissues under
      physiological and disease states. 

PMID- 24563306
TI  - Characterization and a point mutational approach of a psychrophilic lipase from
      an arctic bacterium, Bacillus pumilus.
AB  - A bacterium with lipolytic activity was isolated from the Chukchi Sea within the
      Arctic Ocean. The lipase BpL5 from the isolate, Bacillus pumilus ArcL5, belongs
      to subfamily 4 of lipase family I. The optimum pH and temperature of the
      recombinant enzyme BpL5, as expressed in Escherichia coli, were 9.0 and 20 
      degrees C, respectively. The enzyme retained 85 % of its activity at 5  degrees
      C. There was a significant difference between temperatures for maximal activity
      (20  degrees C) and for protein denaturation (approx. 45  degrees C). The enzyme
      preferred middle-chain (C8) p-nitrophenyl substrates. Two mutants, S139A and
      S139Y, were rationally designed based on the 3D-structure model, and their
      activities were compared with that of the wild type. The both mutants showed
      significantly improved activity against tricaprylin. 

PMID- 24563307
TI  - The development of transgenic mice for the expression of large amounts of human
      lysozyme in milk.
AB  - Human lysozyme (hLYZ) has important potential applications as antimicrobial
      medicine and food additive. To develop a robust expression vector that ensures
      expression of large amounts of hLYZ in milk, here a 26,267 bp chimeric mouse whey
      acidic protein (mWAP)::hLYZ cassette was constructed and used as a mammary gland
      specific expression vector, in which a 3,010 bp genomic sequence in the 24,466 bp
      mWAP gene locus was substituted by a 4,811 bp genomic sequence of hLYZ, exactly
      from the start codon to the stop codon. Corresponding transgenic mice were
      generated, and enzymatically-active hLYZ was expressed at 18.4-35 g l(-1) in the
      milk of most transgenic mouse lines. Our transgenic mice carrying chimeric
      mWAP::hLYZ represent a model system for cost-effective production of hLYZ. 

PMID- 24563308
TI  - Transcriptional repressor role of PocR on the 1,3-propanediol biosynthetic
      pathway by Lactobacillus panis PM1.
AB  - PURPOSE OF WORK: The regulatory role of a transcriptional regulator (PocR) in the
      1,3-propanediol biosynthetic pathway of Lactobacillus panis PM1 contributes to
      the optimization of 1,3-propanediol production by this strain, which potentially
      will lead to 1,3-propanediol manufacturing efficiencies. Lactobacillus panis PM1
      can utilize a 1,3-propanediol (1,3-PDO) biosynthetic pathway, consisting of diol
      dehydratase (PduCDE) and 1,3-PDO dehydrogenase, as a NADH recycling system, to
      survive under various environmental conditions. In this study, we identified a
      key transcriptional repressor (PocR) which was annotated as a transcriptional
      factor of AraC family as part of the 1,3-PDO biosynthetic pathway of L. panis
      PM1. The over-expression of the PocR gene resulted in the significant repression
      (81 %) of pduC (PduCDE large subunit) transcription, and subsequently, the
      decreased activity of PduCDE by 22 %. As a result of the regulation of PduCDE,
      production of both 3-hydroxypropionaldehyde and 1,3-PDO in the PocR over
      expressing strain were significantly decreased by 40 % relative to the control
      strain. These results clearly demonstrate the transcriptional repressor role of
      PocR in the 1,3-PDO biosynthetic pathway.

PMID- 24563309
TI  - Synthesis of a near-infrared fluorescent probe and its application in imaging of
      MCF-7 cells.
AB  - IR-789, a novel near-infrared fluorescent probe, was designed, synthesized, and
      applied to living cells. The probe exhibited better response fluorescence
      characteristics than the only FDA-approved agent, indocyanine green. Cell
      experiments showed that the probe had high affinity and without apparent
      cytotoxicity. Fluorescent image experiments in living MCF-7 cells (human breast
      adenocarcinoma cell line) further demonstrated the potential applications of the
      probe in biological systems. The probe effectively prevented the influence of
      autofluorescence and native cellular species in biological systems. It also
      exhibited high sensitivity, good photostability, and excellent cell membrane
      permeability. 

PMID- 24563310
TI  - General methods for identification of carotenoids.
AB  - General methods for identification of usual carotenoids including C18-HPLC
      retention time and spectroscopic methods, such as absorption spectra, mass
      spectra, NMR spectra, are briefly summarized. 

PMID- 24563311
TI  - Synthetic microbial ecosystems for biotechnology.
AB  - Most highly controlled and specific applications of microorganisms in
      biotechnology involve pure cultures. Maintaining single strain cultures is
      important for industry as contaminants can reduce productivity and lead to longer
      "down-times" during sterilisation. However, microbes working together provide
      distinct advantages over pure cultures. They can undertake more metabolically
      complex tasks, improve efficiency and even expand applications to open systems.
      By combining rapidly advancing technologies with ecological theory, the use of
      microbial ecosystems in biotechnology will inevitably increase. This review
      provides insight into the use of synthetic microbial communities in biotechnology
      by applying the engineering paradigm of measure, model, manipulate and
      manufacture, and illustrate the emerging wider potential of the synthetic ecology
      field. Systems to improve biofuel production using microalgae are also discussed.

PMID- 24563312
TI  - Phenotype microarray technology and its application in industrial biotechnology.
AB  - Phenotype microarray (PM) technology provides an insight into the metabolic
      profiling of microbial cells within 96-well plate system. The PM assay allows for
      cells to be assessed for utilisation of nutrients or sensitivity to toxic
      compounds. The assay utilises a redox sensitive tetrazolium dye which becomes
      irreversibly reduced upon detection of cellular metabolic output, detection is
      synchronous with a colour change from colourless to purple. Output from PM
      technology can be measured visually or quantified by reader the absorbance in
      each well. PM technology has highlighted differences in growth requirements,
      nutrient utilisation, sensitivity to toxins, and genetic diversity in bacteria,
      fungi and mammalian cells. 

PMID- 24563313
TI  - Homo-fermentative production of D-lactic acid by Lactobacillus sp. employing
      casein whey permeate as a raw feed-stock.
AB  - Casein whey permeate (CWP), a lactose-enriched dairy waste effluent, is a viable
      feed stock for the production of value-added products. Two lactic acid bacteria
      were cultivated in a synthetic casein whey permeate medium with or without pH
      control. Lactobacillus lactis ATCC 4797 produced D-lactic acid (DLA) at 12.5 g l(
      1) in a bioreactor. The values of Leudking-Piret model parameters suggested that
      lactate was a growth-associated product. Batch fermentation was also performed
      employing CWP (35 g lactose l(-1)) with casein hydrolysate as a nitrogen
      supplement in a bioreactor. After 40 h, L. lactis produced 24.3 g lactic acid l(
      1) with an optical purity >98 %. Thus CWP may be regarded as a potential feed
      stock for DLA production. 

PMID- 24563314
TI  - In vitro evaluation of human osteoblast-like cell proliferation and attachment on
      nanostructured fluoridated hydroxyapatite.
AB  - The effect of the fluorine content and nano-structure of fluoridated
      hydroxyapatite (FHA) on human osteoblast-like (HO) cell behavior were
      investigated. FHA nanopowders and bulk nanostructured FHA, produced via
      mechanical alloying and two-step sintering, respectively, were used. The
      cytotoxicity of FHA nanopowders was assessed by MTT. Cell attachment to the
      surface of the bulk nanostructured FHA was evaluated by culturing of HO cells.
      Although HO cells proliferated 10 % more in contact with FHA nanopowders compared
      to culture medium without FHA nanopowders, an increase in the fluorine content of
      FHA caused a delay in the cell proliferation by about 2 days. Cell attachment on
      the bulk nanostructured FHA did not change the fluorine content. 

PMID- 24563315
TI  - Expression of human transferrin can be regulated effectively by rabbit
      transferrin regulatory elements in transgenic mice.
AB  - Human transferrin (hTF) belongs to the iron-binding glycoprotein family. It plays
      an important role in iron transport throughout the body. Transgenic mice are a
      good model to study how to produce functional hTF on a large-scale. We have
      improved the expression of hTF and investigated its regulatory mechanism in
      transgenic mice. Three expression constructs were prepared in which hTF
      expression was controlled by different regulatory cassettes of rabbit transferrin
      (rTF). hTF was secreted into serum of transgenic mice when its expression was
      controlled by the rTF promoter and enhancer, whereas the rTF enhancer in tandem
      with the rTF promoter repressed hTF secretion into milk. A significant inverse
      relationship between methylation of the rTF promoter and hTF expression was
      observed in liver, heart, mammary gland, and muscle of transgenic mice. The
      highest concentration of hTF was 700 MUg/ml in milk. 

PMID- 24563316
TI  - Incorporation of adenylate cyclase into membranes of giant liposomes using
      membrane fusion with recombinant baculovirus-budded virus particles.
AB  - Recombinant transmembrane adenylate cyclase (AC) was incorporated into membranes
      of giant liposomes using membrane fusion between liposomes and baculovirus-budded
      virus (BV). AC genes were constructed into transfer vectors in a form fused with
      fluorescent protein or polyhistidine at the C-terminus. The recombinant BVs were
      collected by ultracentrifugation and AC expression was verified using western
      blotting. The BVs and giant liposomes generated using gentle hydration were fused
      under acidic conditions; the incorporation of AC into giant liposomes was
      demonstrated by confocal laser scanning microscopy through the emission of
      fluorescence from their membranes. The AC-expressing BVs were also fused with
      liposomes containing the substrate (ATP) with/without a specific inhibitor (SQ
      22536). An enzyme immunoassay on extracts of the sample demonstrated that cAMP
      was produced inside the liposomes. This procedure facilitates direct introduction
      of large transmembrane proteins into artificial membranes without solubilization.

PMID- 24563317
TI  - Improved dominant selection markers and co-culturing conditions for efficient
      Agrobacterium tumefaciens-mediated transformation of Ustilago scitaminea.
AB  - Ustilago scitaminea is the causal agent of sugar-cane smut disease. There is,
      however, no genetic transformation method for it. Here we report the development
      of an efficient mutagenesis method based on Agrobacterium tumefaciens-mediated
      transformation. To improve transformation efficiency, a range of conditions,
      including the codon-usage preference of the selection marker gene, promoters and
      the culture conditions for transformation were optimized. A strong promoter to
      drive marker gene expression, optimized codon usage of selection marker gene,
      controlled water content and pH of co-culture medium were critical factors
      affecting transformation efficiency. Our findings provide a useful tool for
      genetic analysis of this important plant pathogen. 

PMID- 24563318
TI  - Lithium chloride inhibits TGF-beta1-induced myofibroblast transdifferentiation
      via PI3K/Akt pathway in cultured fibroblasts from Tenon's capsule of the human
      eye.
AB  - Excess scarring of the conjunctiva after glaucoma filtration surgery is a major
      cause of failure. Transforming growth factor (TGF)-beta is critically involved in
      post-operative scarring. Lithium inhibits TGF-beta-induced gene protein
      expression in corneal fibroblasts and inhibits TGF-beta-induced epithelial
      mesenchymal transition. Here, we investigated the effects of LiCl on TGF-beta1
      mediated signaling pathways and on myofibroblast transdifferentiation of human
      Tenon's capsule fibroblasts (HTFs). LiCl treatment reduced expression of TGF
      beta1-induced alpha-SMA expression in HTFs. LiCl also decreased Akt
      phosphorylation induced by TGF-beta1. TGF-beta1-induced alpha-SMA expression was
      significantly decreased by LY294002 and Akt siRNA indicating that these changes
      are mediated by the PI3K/Akt pathway. Thus, LiCl induces the suppression of
      transdifferentiation stimulated by TGF-beta1 by the regulation of PI3K/Akt
      signaling in HTFs. 

PMID- 24563319
TI  - Improvement of trans-sialylation versus hydrolysis activity of an engineered
      sialidase from Trypanosoma rangeli by use of co-solvents.
AB  - Biocatalytic trans-sialylation is relevant for the design of biomimetic
      oligosaccharides such as human milk oligosaccharides. t-Butanol and ionic
      liquids, EAN (ethylammonium nitrate), [MMIm][MeSO4] (1,3-dimethylimidazolium
      methyl sulfate), and [C2OHMIm][PF6] (1-(2-hydroxyethyl)-3-methylimidazolium
      hexafluorophosphate), were examined as co-solvents for the improvement of the
      synthesis versus hydrolysis ratio in the trans-sialylation of lactose, catalysed
      by an engineered sialidase from Trypanosoma rangeli. The use of 25 % (v/v) t
      butanol as co-solvent significantly increased 3'-sialyllactose production by 40 %
      from 1.04 +/- 0.09 to 1.47 +/- 0.01 mM. The synthesis versus hydrolysis ratio
      increased correspondingly by 1.2-times. 1-2.5 % (v/v) EAN or [C2OHMIm][PF6]
      improved the synthesis versus hydrolysis ratio up to 2.5-times but simultaneously
      decreased the 3'-sialyllactose yield, probably due to enzyme inactivation caused
      by the ionic liquid. [MMIm][MeSO4] had a detrimental effect on the trans
      sialylation yield and on the ratio between synthesis and hydrolysis. 

PMID- 24563320
TI  - Heat-shock protein beta 1 regulates androgen-mediated bovine myogenesis.
AB  - To elucidate the functional significance of heat-shock protein beta 1 (HSPB1) in
      androgen-mediated myogenesis of bovine cells, we conducted 'loss and gain of
      function of HSPB1' assays by siRNA inhibition and gene overexpression. siRNA
      inhibition of HSPB1 expression reduced the expression of desmin (a myogenic
      marker) and repressed the formation of myotubes in cells induced for myogenic
      differentiation. In contrast, overexpression of HSPB1 enhanced the expression of
      desmin and accelerated formation of myotubes. The loss and gain of HSPB1 function
      was closely associated with the expression level of androgen receptor (AR). Our
      findings suggest that HSPB1 mediates androgen signaling by binding directly to AR
      and then enhancing androgen-mediated myogenesis in myogenic cells. 

PMID- 24563321
TI  - Effect of miR-205 on 3T3-L1 preadipocyte differentiation through targeting to
      glycogen synthase kinase 3 beta.
AB  - MiR-205 plays an important role during adipogenesis by modulating the Wnt
      signaling pathway. Here, we report that miR-205 can regulate the differentiation
      of 3T3-L1 preadipocyte cells by targeting glycogen synthase kinase 3 beta (GSK
      3beta), which is a negative regulatory factor of Wnt signaling. When transiently
      overexpressed in 3T3-L1 cells, miR-205 suppressed the translation of GSK-3beta,
      resulting in increased expression of beta-catenin, which can promote cell
      proliferation by facilitating the transcription of the Wnt target genes cyclin D1
      and c-Myc. However, stable overexpression of miR-205 in 3T3-L1 cells did not show
      any apparent inhibitory effect on adipogenic differentiation. While endogenous
      miR-205 was inhibited in 3T3-L1 cells, the adipogenesis marker gene, C/EBPalpha,
      was significantly activated and more lipid droplets appeared in differentiated
      adipocytes. However, systemic silencing of miR-205 in mice by using a locked
      nucleic-acid-modified oligonucleotide (LNA-antimiR) did not lead to any
      observable increase in adipose tissue differentiation, implying that, as opposed
      to the findings from 3T3-L1 cells, miR-205 is dispensable for adipose tissue
      development in mice. 

PMID- 24563322
TI  - In vitro preparation of amelogenin nanoparticles carrying nucleic acids.
AB  - Amelogenin, a matrix protein involved in biomineralization of enamel, can self
      assemble to form nanospheres in a pH-dependent manner. Nucleic acids (single
      stranded, double-stranded, and plasmid DNA, as well as RNA) could be co
      precipitated with amelogenin, demonstrating a strong binding of nucleic acids to
      amelogenin. The amounts of co-precipitated nucleic acids were analyzed and
      binding levels upto 90 MUg DNA/mg amelogenin was achieved. The co-precipitation
      could also be carried out in a bacterial cell homogenate, and no bacterial
      proteins were found in the amelogenin aggregates, suggesting specificity for
      nucleic acid binding. Dynamic light scattering showed that amelogenin nanosphere
      structure is maintained upon DNA binding with an upto 2.6 nm increase in
      diameter. The reported binding of nucleic acids to amelogenin can be explored
      practically for nucleic acid separation. 

PMID- 24563323
TI  - Characterization of a novel GH2 family alpha-L-arabinofuranosidase from
      hyperthermophilic bacterium Thermotoga thermarum.
AB  - The 2,367-bp ORF of TtAFase from Thermotoga thermarum DSM 5069 encodes a
      calculated 90-kDa alpha-L-arabinofuranosidase (TtAFase), which does not belonging
      to any reported glycosyl hydrolase families alpha-L-arabinofuranosidases in the
      database and represents a novel one of glycosyl hydrolase family 2. The purified
      recombinant TtAFase produced in Escherichia coli BL21 (DE3) had optimum activity
      at pH 5.5 and at 80  degrees C. It was stable up to 80  degrees C and from pH 4.5
      8.5. Kinetic experiments at 80  degrees C with p-nitrophenyl alpha-L
      arabinofuranoside as a substrate gave a K m of 0.77 mM, V max of 2.3 MUmol mg(-1)
      min(-1) and k cat of 4.5 s(-1). The enzyme had no apparent requirement of metal
      ions for activity, and its activity was significantly inhibited by Cu(2+) or
      Zn(2+). 

PMID- 24563324
TI  - Bioreduction and disproportionation of cyclohex-2-enone catalyzed by ene
      reductase OYE-1 in 'micro-aqueous' organic solvents.
AB  - The bioreduction and disproportionation of cyclohex-2-enone catalyzed by Old
      Yellow Enzyme 1 was investigated in presence of organic (co)solvents. Whereas the
      NADH-dependent bioreduction activity strongly decreased at elevated co-solvent
      concentrations due to the insolubility of the nicotinamide-cofactor, the NADH
      free disproportionation was significantly improved in water-immiscible organic co
      solvents at 90 % (v/v) with near-quantitative conversion. This positive effect
      was attributed to removal of the inhibiting co-product, phenol, from the enzyme's
      active site. The best co-solvents show high lipophilicity (logP) and a high
      potential to solubilize phenol (Kphenol). As a predictive parameter, the ratio of
      logP/Kphenol should be preferably >=100. 

PMID- 24563325
TI  - The effect of a single 2 h bout of aerobic exercise on ectopic lipids in skeletal
      muscle, liver and the myocardium.
AB  - AIMS/HYPOTHESIS: Ectopic lipids are fuel stores in non-adipose tissues (skeletal
      muscle [intramyocellular lipids; IMCL], liver [intrahepatocellular lipids; IHCL]
      and heart [intracardiomyocellular lipids; ICCL]). IMCL can be depleted by
      physical activity. Preliminary data suggest that aerobic exercise increases IHCL.
      Data on exercise-induced changes on ICCL is scarce. Increased IMCL and IHCL have
      been related to insulin resistance in skeletal muscles and liver, whereas this
      has not been documented in the heart. The aim of this study was to assess the
      acute effect of aerobic exercise on the flexibility of IMCL, IHCL and ICCL in
      insulin-sensitive participants in relation to fat availability, insulin
      sensitivity and exercise capacity. METHODS: Healthy physically active men were
      included. VO(2max) was assessed by spiroergometry and insulin sensitivity was
      calculated using the HOMA index. Visceral and subcutaneous fat were separately
      quantified by MRI. Following a standardised dietary fat load over 3 days, IMCL,
      IHCL and ICCL were measured using MR spectroscopy before and after a 2 h exercise
      session at 50-60% of VO(2max). Metabolites were measured during exercise.
      RESULTS: Ten men (age 28.9 +/- 6.4 years, mean +/- SD; VO(2max) 56.3 +/- 6.4 ml
      kg(-1) min(-1); BMI 22.75 +/- 1.4 kg/m(2)) were recruited. A 2 h exercise session
      resulted in a significant decrease in IMCL (-17 +/- 22%, p = 0.008) and ICCL (-17
      +/- 14%, p = 0.002) and increase in IHCL (42 +/- 29%, p = 0.004). No significant
      correlations were found between the relative changes in ectopic lipids, fat
      availability, insulin sensitivity, exercise capacity or changes of metabolites
      during exercise. CONCLUSIONS/INTERPRETATION: In this group, physical exercise
      decreased ICCL and IMCL but increased IHCL. Fat availability, insulin
      sensitivity, exercise capacity and metabolites during exercise are not the only
      factors affecting ectopic lipids during exercise.

PMID- 24563326
TI  - Sensitivity to Phonological Universals: The Case of Stops and Fricatives.
AB  - Linguistic evidence suggests that syllables like bdam (with stop-stop clusters)
      are less preferred than bzam (with stop-fricative combinations). Here, we
      demonstrate that English speakers manifest similar preferences despite no direct
      experience with either structure. Experiment 1 elicited syllable count for
      auditory materials (e.g., does bzam have one syllable or two?); Experiment 2
      examined the AX discrimination of auditory stimuli (e.g., is bzam = bezam?);
      whereas Experiment 3 repeated this task using printed materials. Results showed
      that syllables that are dispreferred across languages (e.g., bdam) were prone to
      misidentification relative to preferred syllables (e.g., bzam). The emergence of
      this pattern irrespective of stimulus modality--for auditory and printed
      materials--suggests that misidentification does not solely stem from a phonetic
      failure. Further, the effect remained significant after controlling for various
      statistical properties of the materials. These results suggest that speakers
      possess broad linguistic preferences that extend to syllables they have never
      encountered before.

PMID- 24563327
TI  - Up-regulation and worse prognostic marker of cytoplasmic TARBP2 expression in
      obstinate breast cancer.
AB  - Expression of trans-activation-responsive-RNA-binding protein 2 (TARBP2) varied
      from normal cell lines to various cancer cell lines. The discussion of TARBP2
      serve as tumor suppressor or tumor promotor goes on. However, its expression in
      breast cancer remains unknown. The aim of present study was to assess the
      expression of cytoplasm TARBP2 as potential prognostic marker in breast cancer.
      We further investigated cytoplasm TARBP2 could be a novel target in treatment for
      late-stage breast cancer and triple-negative breast cancer (TNBC). A total of
      patients with breast cancer were involved in our cohort. Immunohistochemical
      staining for TARBP2 on tissue microarray and western blot were used.
      Immunohistochemistry showed that cytoplasm TARBP2 was frequently up-regulated in
      breast carcinoma. This finding was in line with the result of western blot
      analysis. Further investigation showed that cytoplasm TARBP2 expression in non
      TNBC was higher than that of their adjacent normal breast tissues (NBT), and TNBC
      was the highest of the three groups. The positive expression of cytoplasm TARBP2
      in stage III breast cancer, stage I-II breast cancer, and NBT decreased
      gradually. In addition, univariate and multivariate survival analysis revealed
      cytoplasm TARBP2 was an independent prognostic factor for breast cancer. Breast
      cancer patients with cytoplasm TARBP2 expression had poorer disease-free survival
      and overall survival, and similar results were obtained in TNBC group and stage
      III breast cancer group. Our results provide convincing evidence for the first
      time that the expression of cytoplasm TARBP2 is up-regulated in breast cancer.
      Breast cancer patients with TARBP2 cytoplasm expression have unfavorable
      prognosis. Patients of TNBC and late-stage breast cancer with higher cytoplasm
      TARBP2 expression have an unfavorable prognosis. 

PMID- 24563329
TI  - The PNPLA3 Ile148Met interacts with overweight and dietary intakes on fasting
      triglyceride levels.
AB  - The Ile148Met (rs738409, G-allele) in the patatin-like phospholipase domain
      containing protein 3 gene (PNPLA3) associates with liver fat content and may lead
      to loss-of-function (hydrolysis) or gain-of-function (CoA-dependent
      lysophosphatidic acid acyltransferase) defects. PNPLA3 is up-regulated by dietary
      carbohydrates, and interactions between rs738409 and carbohydrates, and sugar and
      omega6:omega3-polyunsaturated fatty acid (PUFA) ratio on hepatic fat accumulation
      have been reported. We examined interaction between rs738409 and overweight, and
      between rs738409 and dietary intakes (carbohydrates, sucrose and omega6:omega3
      PUFA ratio), on fasting triglyceride levels. From the Malmo Diet and Cancer Study
      Cardiovascular Cohort, 4,827 individuals without diabetes aged 58 +/- 6 years,
      2,346 with BMI <= 25 kg/m(2) and 2,478 with BMI > 25 kg/m(2), were included in
      cross-sectional analyses. Dietary data were collected by a modified diet history
      method. Overweight modified the association between rs738409 and fasting
      triglyceride levels (P interaction = 0.003). G-allele associated with lower
      triglycerides only among overweight individuals (P = 0.01). Nominally,
      significant interaction on triglyceride levels was observed between rs738409 and
      sucrose among normal-weight individuals (P interaction = 0.03). G-allele
      associated with lower triglycerides among overweight individuals in the lowest
      tertiles of carbohydrate and omega6:omega3-PUFA ratio (P = 0.04 and P = 0.001)
      and with higher triglycerides among normal-weight individuals in the highest
      tertile of sucrose (P = 0.001). We conclude that overweight and dietary sucrose
      may modify the association between rs738409 and fasting triglyceride levels. 

PMID- 24563328
TI  - Expression profiling of breast cancer patients treated with tamoxifen: prognostic
      or predictive significance.
AB  - Approximately 70% of breast cancers are estrogen receptor (ER) positive, and
      interfering with estrogen action with tamoxifen has been the treatment of choice
      for ER-positive breast cancer patients. However, about a third of patients
      treated with tamoxifen will experience a recurrence of cancer. The expression
      analysis of selected genes involved in tamoxifen/estrogen and receptor tyrosine
      kinase signaling pathways can help to further decipher mechanisms of recurrence
      in ER+ tumors and contribute to the development of prognostic and possibly
      predictive biomarkers. We selected seven genes (ESR1, CCND1, MYC, HER2, AKT1,
      AIB1 and NCOR1), which are components of these pathways. A case-control study was
      designed. All patients in the control group had received standard adjuvant
      tamoxifen treatment for 5 years without any evidence of recurrence. Patients in
      the case group had experienced an early recurrence of cancer while receiving
      tamoxifen treatment. Expression levels of selected genes in both groups were
      compared. Expression levels of CCND1 (p < 0.001), HER2 (p < 0.001), AKT1 (p =
      0.038) and AIB1 (p = 0.004) were significantly higher in recurrent tumors
      compared to non-recurrent tumors, while expression levels of NCOR1 (p < 0.001)
      were significantly lower in recurrent tumors. In multivariable analysis, CCND1 (p
      < 0.001), HER2 (p = 0.003), AIB1 (p = 0.036) and NCOR1 (p = 0.002) remained
      significant predictors of recurrence. Expression levels of CCND1, HER2, AIB1 and
      NCOR1 were detected as independent predictors of recurrence in this cohort of
      tamoxifen-treated patients. Further work should be done to validate the
      predictive value of this gene profile for tamoxifen response.

PMID- 24563330
TI  - Vascular adhesion molecules in men with obstructive sleep apnea: associations
      with obesity and metabolic syndrome.
AB  - INTRODUCTION: Mechanisms linking obstructive sleep apnea (OSA) to vascular
      diseases as well as obesity and metabolic syndrome are not clear. The purpose of
      the study was to evaluate levels of vascular adhesion molecules (soluble vascular
      cell adhesion molecules-1 (sVCAM-1) and E-selectin) in men with obstructive sleep
      apnea and control subjects and to determine their relations with obesity and
      metabolic syndrome. METHODS: Men with OSA and controls matched for age were
      included in the study. Overnight polysomnography was performed. Body mass index
      (BMI) and all the components of metabolic syndrome were evaluated. Serum levels
      of sVCAM-1 and E-selectin were measured by enzyme-linked immunosorbent assay.
      Data presented as median (25th and 75th percentiles). RESULTS: Levels of sVCAM-1
      (698.2 (627.6-798.2) vs 565.5 (518.8-678.1) ng/ml, p=0.003) and E-selectin (64.9
      (50.1-83.1) vs 49.7 (39.8-59.5) ng/ml, p=0.017) were higher in the OSA group
      compared to the controls. Half of OSA patients had metabolic syndrome. Serum
      levels of sVCAM-1 and E-selectin did not differ in OSA patients with and without
      metabolic syndrome. Concentrations of both vascular adhesion molecules correlated
      with oxygen desaturation index (ODI), but the relation was no more significant
      after adjustment for all the components of metabolic syndrome. After adjustment
      for BMI, sVCAM-1 levels positively correlated with oxygen desaturation index
      (r=0.331, p=0.009). CONCLUSIONS: Serum levels of sVCAM-1 and E-selectin were
      increased in the OSA patient group compared to the controls. sVCAM-1 showed
      relation with ODI after adjustment for BMI suggesting that it could contribute to
      development of cardiovascular consequences in OSA patients.

PMID- 24563331
TI  - Sleep studies in children on long-term non-invasive respiratory support.
AB  - PURPOSE: The aim of this study was to assess the impact of changes in respiratory
      support (RS) settings recommended after a titration polysomnography (PSG), in
      terms of daytime symptoms and quality of life. METHODS: A retrospective chart
      review of all RS (CPAP and bi-level ventilation) titration studies was carried
      out at our tertiary paediatric sleep laboratory in the past 5 years. All patients
      with at least two studies in the past 5 years were included in the analysis.
      Parents completed the obstructive sleep apnoea (OSA)-18 and Paediatric Daytime
      Sleepiness Scale (PDSS) questionnaires on the night of each PSG. Results are
      presented as means (SD). RESULTS: A total of 42 patients (25 on CPAP and 17 on bi
      level ventilation, age 11 (6) years) had 71 pairs of titration studies (41 CPAP
      and 30 bi-level). Changes in RS settings were recommended in 27 of 41 (65%) CPAP
      studies and 11 of 30 (36%) bi-level studies. Overall, changes were fully
      implemented by the treating physician in 55% of cases. There was an improvement
      in total OSA-18 score between studies in 48% of the paired CPAP studies and 65%
      of bi-level studies. OSA-18 scores improved in 47% of the studies where any
      recommended change had been implemented versus 0% of those where none of the
      recommended changes had been made (p=0.1). CONCLUSIONS: Titration studies
      frequently led to recommendations for a change in RS settings in these patients
      on long-term RS. Symptom scores were more likely to improve if recommendations
      for change were implemented by the time of the follow-up study.

PMID- 24563332
TI  - PACAP-38 infusion causes sustained vasodilation of the middle meningeal artery in
      the rat: possible involvement of mast cells.
AB  - BACKGROUND: In healthy human volunteers and in migraineurs, pituitary adenylate
      cyclase-activating polypeptide-38 (PACAP-38) infusion caused sustained
      vasodilation of the middle meningeal artery (MMA) and an immediate as well as a
      delayed headache. All the study subjects experienced facial flushing. Mast cells
      (MCs) might have a role in the long-lasting effect of PACAP-38 infusion. We
      hypothesized that in mast cell-depleted (MCD) rats the vascular responses to
      PACAP-38 would be lesser than in control rats because of a lack of vasodilatory
      products released during MC degranulation. METHODS: MCs were depleted by chronic
      treatment with compound 48/80. The effect of 20 minutes' intravenous (i.v.)
      infusion of calcitonin gene-related peptide (CGRP), PACAP-38, PACAP(6-38) (PAC-1
      receptor antagonist) and PACAP-27 on the diameter of the MMA and on mean arterial
      blood pressure (MABP) in control and MCD rats was recorded by using the genuine
      closed-cranial window (CCW) model. Vasoactive intestinal polypeptide (VIP)
      infusion was given only in control rats. A combination of the histamine H1
      receptor antagonist mepyramine (4 mg kg(-1) i.v.) and the H2 receptor antagonist
      famotidine (1 mg kg(-1) i.v.) was given 10 minutes prior to PACAP-38 infusion.
      Increasing doses of PACAP-38, PACAP-27 and VIP were infused through the
      intracarotid artery (i.c.) in control and MCD rats to see the direct effects of
      these peptides on MMA diameter change. RESULTS: There was no significant change
      in CGRP-induced MMA diameter increase in control and MCD rats, and the dilated
      MMA immediately returned back to baseline after stopping the infusion. The
      delayed MMA dilation induced by PACAP-38 was abolished in MCD and antihistamine
      (AH)-pretreated rats. Compared to PACAP-38, the PACAP-27 i.v. infusion gave
      smaller peak dilation of MMA in control rats. In MCD rats, PACAP-27 did not
      induce any significant dilation. VIP i.v. infusion reduced MABP but did not
      dilate MMA significantly. PACAP(6-38), which is a potent MC degranulator, also
      gave a significant delayed dilation of MMA. PACAP-38 i.c. responses (direct
      receptor mediated response) were not affected by MC depletion. Only the maximum
      response (% E max) value of PACAP-27 (i.c.) was significantly lower in MCD rats
      compared to control rats. CONCLUSIONS: The delayed MMA dilatory responses to
      PACAP-38 infusion were attenuated in MCD and AH-pretreated rats, indicating a
      role of the MC mediator-histamine in PACAP-38-induced delayed dilation of MA.

PMID- 24563333
TI  - Sulfonylureas: a new look at old therapy.
AB  - Sulfonylurea compounds were the first available oral antidiabetic agents and they
      remain an important tool in our quest for optimal glucose control. The
      sulfonylureas stimulate the release of insulin from pancreatic beta-cells and
      have a number of extrapancreatic effects, including decreasing hepatic insulin
      clearance and reducing glucagon secretion in patients with type 2 diabetes.
      Although these agents have been the mainstay of pharmacotherapy for patients with
      type 2 diabetes mellitus (T2DM), their safety and clinical utility has been a
      matter of active debate in recent years, as their use is associated with risks of
      hypoglycemia and weight gain. We review the discovery and mechanisms of action of
      sulfonylureas, and the results of clinical trials to provide practical
      information on the pros and cons of their use in clinical practice. This review
      addresses advances in our understanding of mechanisms of action of sulfonylurea
      agents, their efficacy in T2DM, side effects, and impact on cardiovascular
      disease outcomes. 

PMID- 24563335
TI  - Survivin mRNA expression in blood as a predictor of the response to EGFR-tyrosine
      kinase inhibitors and prognosis in patients with non-small cell lung cancer.
AB  - The epidermal growth factor receptor (EGFR) mutations have been proven to be a
      reliable predictive marker for the response to EGFR-tyrosine kinase inhibitors
      (TKIs) in patients with non-small cell lung cancer (NSCLC). However, the
      responses to EGFR-TKIs vary even among patients with EGFR mutation. Recent study
      showed that survivin overexpression attenuated EGFR-TKI-induced apoptosis and
      inhibited the antitumor effect of EGFR-TKIs on EGFR mutation NSCLC cells. We
      investigated the role of survivin mRNA expression in peripheral blood on
      predicting response and prognosis in NSCLC patients treated with EGFR-TKIs.
      Survivin mRNA expression levels in blood was detected using quantitative real
      time-PCR assay in 62 patients with advanced NSCLC before (D0) and 4 weeks after
      treatment of EGFR-TKIs (D4w). The associations between survivin mRNA expression
      in blood and tumor response to treatment, time to progression (TTP), and overall
      survival (OS) were analyzed. Blood survivin mRNA levels at D0 and D4w were
      significantly higher in patients with progressive disease than in those with
      partial response and stable disease. The detections of blood survivin mRNA
      positivity at D0 and D4w were associated with unfavorable response to EGFR-TKIs
      treatment and shorter TTP and OS. Multivariate Cox analysis showed that blood
      survivin mRNA positivity before and 4 weeks after EGFR-TKIs treatment were
      independent predictor for worse TTP and OS. In conclusion, Blood survivin mRNA
      positivity was strongly related to a poor treatment outcome of EGFR-TKIs and may
      be a potential non-invasive biomarker for NSCLC treatment.

PMID- 24563334
TI  - LRRC4 haplotypes are associated with pituitary adenoma in a Chinese population.
AB  - Pituitary adenoma results from accumulation of multiple genetic and/or epigenetic
      aberrations such as GNAS, MEN1, CNC, and FIPA. LRRC4 is relatively tissue
      specific expressed gene in the normal brain and downregulated expression in
      glioma (87.5%), meningioma (80.9%), and pituitary adenoma (85.5%). It has been
      suggested that the aberrant expression of LRRC4 contributes to tumorigenesis in
      glioma. However, little is known yet about association between LRRC4 and risk of
      pituitary adenoma. In this study, we genotyped three LRRC4 haplotype-tagging SNPs
      (htSNP) by direct sequencing in case-control studies, which included 183 Han
      Chinese patients diagnosed with pituitary adenoma and 183 age-, gender-matched,
      and geographically matched Han Chinese controls. Haplotypes were reconstructed
      according to the genotyping data and linkage disequilibrium status of the htSNP.
      We observed statistically significant differences regarding the genotype TT + CT
      of rs6944446 in the NCA. Haplotype AC of rs3823994-rs6944446 is suggested to have
      a protective effect in the development of pituitary adenoma (OR 0.339; 95% CI
      0.123-0.934). However, haplotype GT of rs3808058-rs6944446 (OR 1.575; 95% CI
      1.048-2.368) and AGT of rs3823994-rs6944446-rs3808058 (OR 1.673; 95% CI 1.056
      2.651) might be a risk factor for pituitary adenoma development. In a brief, the
      results support the hypothesis that polymorphisms or haplotypes in the LRRC4 may
      have important research significance and could be used to predict the risk of
      pituitary adenoma.

PMID- 24563336
TI  - Oxymatrine triggers apoptosis by regulating Bcl-2 family proteins and activating
      caspase-3/caspase-9 pathway in human leukemia HL-60 cells.
AB  - With the objective of identifying promising antitumor agents for human leukemia,
      we carried out to determine the anticancer ability of oxymatrine on the human
      leukemia HL-60 cell line. In vitro experiments demonstrated that oxymatrine
      reduced the proliferation of HL-60 cells in a dose- and time-dependent manner via
      the induction of apoptosis and cell cycle arrest at G2/M and S phases. The
      proteins involved in oxymatrine-induced apoptosis in HL-60 cells were also
      examined using Western blot. The increase in apoptosis upon treatment with
      oxymatrine was correlated with downregulation of anti-apoptotic Bcl-2 expression
      and upregulation of pro-apoptotic Bax expression. Furthermore, oxymatrine induced
      the activation of caspase-3 and caspase-9 and the cleavage of poly(ADP-ribose)
      polymerase (PARP) in HL-60 cells. In addition, pretreatment with a specific
      caspase-3 (Z-DEVD-FMK) or caspase-9 (Z-LEHD-FMK) inhibitor significantly
      neutralized the pro-apoptotic activity of oxymatrine in HL-60 cells,
      demonstrating the important role of caspase-3 and caspase-9 in this process.
      Taken together, these results indicated that oxymatrine-induced apoptosis may
      occur through the activation of the caspase-9/caspase-3-mediated intrinsic
      pathway. Therefore, oxymatrine may be a potential candidate for the treatment of
      human leukemia. 

PMID- 24563337
TI  - Molecular mechanism of inhibitory effects of C-phycocyanin combined with all
      trans-retinoic acid on the growth of HeLa cells in vitro.
AB  - We studied the effects of all-trans-retinoic acid (ATRA), C-phycocyanin (C-PC),
      or ATRA+C-PC on the growth of cervical cells (HeLa cells), cell cycle
      distribution, and apoptosis. The anticancer mechanism of the drug combination was
      revealed. MTT assay was adopted to determine the effects of C-PC and ATRA on the
      growth of HeLa cells. The expression quantities of cyclin-dependent kinase (CDK)
      4, cyclin D1, Bcl-2, caspase-3, and CD59 were determined by in situ
      hybridization, immunofluorescence, immunohistochemistry staining, Western blot,
      and RT-PCR. TUNEL assay was adopted to determine the cellular apoptosis levels.
      Both C-PC and ATRA could inhibit the growth of HeLa cells, and the combination of
      ATRA+C-PC functioned cooperatively to induce apoptosis in HeLa cells. The dosage
      of ATRA was reduced when it cooperated with C-PC to reduce the toxicity. ATRA
      treated with C-PC could induce more cell cycle arrests than the single drug used
      by decrease in cyclin D1 and CDK4 expression. The combination of the two drugs
      could upregulate caspase-3 and downregulate the Bcl-2 gene and induce cell
      apoptosis. Moreover, the combination therapy has an important immunological
      significance in decreased expression of the CD59 protein. Singly, C-PC or ATRA
      could inhibit the growth of HeLa cells, and the effects of treatment were further
      enhanced in the combination group. In combination with C-PC, the dosage of ATRA
      was effectively reduced. The C-PC + ATRA combination might take effect by
      inhibiting the progress of the cell cycle, inducing cell apoptosis and promoting
      complement-mediated cytolysis.

PMID- 24563339
TI  - Immunohistochemistry as a quick screening method for clinical detection of
      BRAF(V600E) mutation in melanoma patients.
AB  - With the increased uses of targeted therapeutics, diagnostic detection of target
      mutations becomes essential for the effective clinical applications of targeted
      therapeutics. Currently, there are two types of methods detecting target
      mutations in clinics: one is based on DNA sequence and the other uses the newly
      developed mutation-specific antibodies recognizing mutated proteins. Each method
      has its own advantages and disadvantages. Here, we explored the sensitivity and
      specificity of a new commercially available BRAF(V600E) mutation-specific mouse
      monoclonal antibody. Using routine manual immunohistochemistry (IHC), we tested
      tumor tissues from 38 melanoma patients. For those melanoma tissues with abundant
      endogenous melanin, we pretreated the tumor tissues with 3 % hydrogen peroxide to
      remove melanin for reliable signal detection. We also performed DNA sequencing
      and ARMS-PCR analyses for these 38 tumor samples. Comparing to the results from
      DNA-based detection methods, the IHC method with this BRAF(V600E) mutation
      specific antibody displayed 100 % sensitivity and 92.9 % specificity. Hence, this
      IHC detection is sensitive for clinic uses as a simple, fast, inexpensive, and
      reliable method to screen cancer patients for the BRAF(V600E) mutation and could
      be easily adapted for use in most hospital pathology laboratories.

PMID- 24563341
TI  - The nuclear envelope and cancer: a diagnostic perspective and historical
      overview.
AB  - Cancer has been diagnosed for millennia, but its cellular nature only began to be
      understood in the mid-nineteenth century when advances in microscopy allowed
      detailed specimen observations. It was soon noted that cancer cells often
      possessed nuclei that were altered in size and/or shape. This became an important
      criterion for cancer diagnosis that continues to be used today. The mechanisms
      linking nuclear abnormalities and cancer only started to be understood in the
      second half of the twentieth century, with the discovery of nuclear lamina
      composition differences in cancer cells compared to normal cells. The nuclear
      envelope, rather than providing a mere physical barrier between the genetic
      material in the nucleus and the cytoplasm, is a very important functional hub for
      many cellular processes. In this review we give an overview of the links between
      cancer biology and nuclear envelope, from the early days of microscopy until the
      present day's understanding of some of the molecular mechanisms behind those
      links. 

PMID- 24563338
TI  - Bone marrow mast cell density correlates with serum levels of VEGF and CXC
      chemokines ENA-78 and GRO-alpha in multiple myeloma.
AB  - Angiogenesis is a crucial process in growth and progression of multiple myeloma
      (MM). Mast cells (MCs) play an important role in MM angiogenesis. Various
      angiogenic mediators secreted by MCs regulate endothelial cell proliferation and
      function. Among them, ELR(+) CXC chemokines, such as growth-related oncogen-alpha
      (GRO-alpha) and epithelial neutrophil activating protein-78 (ENA-78), have been
      described as potential mediators in regulation of angiogenesis. The purpose of
      the study was to quantify MCs in bone marrow (BM) biopsies of MM patients,
      expressed as MC density (MCD), and correlate it with serum concentrations of
      vascular endothelial factor (VEGF), GRO-alpha, ENA-78. Fifty-four newly diagnosed
      MM patients and 22 healthy controls were studied. Tryptase was used for the
      immunohistochemical stain of MCs. VEGF, GRO-alpha, and ENA-78 were measured in
      sera by ELISA. MCD and serum levels of GRO-alpha, ENA-78, and VEGF were
      significantly higher in MM patients compared to controls (p<0.001 in all cases).
      MCD was significantly increasing with increased stage of the disease (p<0.001).
      Furthermore, significant correlations were found between MCD with VEGF, GRO
      alpha, and ENA-78. These findings support that MCs participate in the
      pathophysiology of MM and is implicated in the angiogenic process and disease
      progression.

PMID- 24563342
TI  - The role of the nuclear lamina in cancer and apoptosis.
AB  - Not long after the discovery of lamin proteins, it became clear that not all
      lamin subtypes are ubiquitously expressed in cells and tissues. Especially, A
      type lamins showed an inverse correlation with proliferation and were thus
      initially called statins. Here we compare the findings of both A- and B-type
      lamin expression in various normal tissues and their neoplastic counterparts.
      Based on immunocytochemistry it becomes clear that lamin expression patterns are
      much more complicated than initially assumed: while normally proliferative cells
      are devoid of A-type lamin expression, many neoplastic tissues do show prominent
      A-type lamin expression. Conversely, cells that do not proliferate can be devoid
      of lamin expression. Yet, within the different types of tissues and tumors,
      lamins can be used to distinguish between tumor subtypes. The link between the
      appearance of A-type lamins in differentiation and the appearance of A-type
      lamins in a tumor likely relates the proliferative capacity of the tumor to its
      differentiation state.While lamins are targets for degradation in the apoptotic
      process, and accordingly are often used as markers for apoptosis, intriguing
      studies on an active role of lamins in the initiation or the prevention of
      apoptosis have been published recently and give rise to a renewed interest in the
      role of lamins in cancer. 

PMID- 24563340
TI  - The baroreceptor as a therapeutic target for heart failure.
AB  - Sympathoactivation is a prominent feature of heart failure (HF). Its role in
      cardiac remodeling and arrhythmogenesis is well-recognized today, although
      incomplete understanding of autonomic mechanisms was a barrier to development of
      contemporary medical therapies. Despite widespread availability of drugs and
      devices, mortality and morbidity in HF remain unacceptably high. Recognition of
      an additional phenotype, HF with preserved ejection fraction (EF), poses
      additional challenges. New treatment options are required. Electrical modulation
      of the central nervous system with baroreflex activation therapy offers a new
      approach. Activation of this afferent pathway induces the central nervous system
      to rebalance autonomic modulation of the cardiovascular system. Results in animal
      models of HF demonstrating increased survival and beneficial cardiac remodeling
      recently led to a clinical feasibility study in HF with reduced EF wherein the
      clinical course of patients dramatically improved. Results in resistant
      hypertension patients further suggest potential for benefit in HF with preserved
      EF. 

PMID- 24563343
TI  - The diagnostic pathology of the nuclear envelope in human cancers.
AB  - Cancer is still diagnosed on the basis of altered tissue and cellular morphology.
      The criteria that pathologists use for diagnosis include many morphologically
      distinctive alterations in the nuclear envelope (NE). With the expectation that
      diagnostic NE changes will have biological relevance to cancer, a classification
      of the various types of NE structural changes into three groups is proposed. The
      first group predicts chromosomal instability. The changes in this group include
      pleomorphism of lamina size and shape, as if constraints to maintain a spherical
      shape were lost. Also characteristic of chromosomal instability are the presence
      of micronuclei, a specific structural feature likely related to the newly
      described physiology of chromothripsis. The second group is predicted to be
      functionally important during clonal evolution, because the NE changes in this
      group are conserved during the clonal evolution of genetically unstable tumors.
      Two examples of this group include increased ratio of nuclear volume to
      cytoplasmic volume and the relatively fragile nuclei of small-cell carcinomas.
      The third and most interesting group develops in a near-diploid, genetically
      stable background. Many of these (perhaps ultimately all) are directly related to
      the activation of particular oncogenes. The changes in this group so far include
      long inward folds of the NE and spherical invaginations of cytoplasm projecting
      partially into the nucleus ("intranuclear cytoplasmic inclusions"). This group is
      exemplified by papillary thyroid carcinoma in which RET and TRK tyrosine kinases,
      and probably B-Raf mutations, directly lead to diagnostic longitudinal folds of
      the lamina ("nuclear grooves") and intranuclear cytoplasmic inclusions. B-Raf
      activation may also be linked to intranuclear cytoplasmic inclusions in melanoma
      and to nuclear grooves in Langerhans cell histiocytosis. Nuclear grooves in
      granulosa cell tumor may be related to mutations in the FOXL2 oncogene.
      Uncovering the precise mechanistic basis for any of these lamina alterations
      would provide a valuable objective means for improving diagnosis, and will likely
      reflect new types of functional changes, relevant to particular forms of cancer. 

PMID- 24563344
TI  - Nuclear morphometry, epigenetic changes, and clinical relevance in prostate
      cancer.
AB  - Nuclear structure alterations in cancer involve global genetic (mutations,
      amplifications, copy number variations, translocations, etc.) and epigenetic (DNA
      methylation and histone modifications) events that dramatically and dynamically
      spatially change chromatin, nuclear body, and chromosome organization. In
      prostate cancer (CaP) there appears to be early (<50 years) versus late (>60
      years) onset clinically significant cancers, and we have yet to clearly
      understand the hereditary and somatic-based molecular pathways involved. We do
      know that once cancer is initiated, dedifferentiation of the prostate gland
      occurs with significant changes in nuclear structure driven by numerous genetic
      and epigenetic processes. This review focuses upon the nuclear architecture and
      epigenetic dynamics with potential translational clinically relevant applications
      to CaP. Further, the review correlates changes in the cancer-driven epigenetic
      process at the molecular level and correlates these alterations to nuclear
      morphological quantitative measurements. Finally, we address how we can best
      utilize this knowledge to improve the efficacy of personalized treatment of
      cancer. 

PMID- 24563345
TI  - "To be or not to be in a good shape": diagnostic and clinical value of nuclear
      shape irregularities in thyroid and breast cancer.
AB  - Variation in both nuclear shape and size ("pleomorphism"), coupled with changes
      in chromatin amount and distribution, remains the basic criteria for microscopy
      in a cytologic diagnosis of cancer. The biological determinants of nuclear shape
      irregularities are not clarified, so, rather than on the genesis of nuclear
      irregularities, we here focus our attention on a descriptive analysis of nuclear
      pleomorphism. We keep in mind that evaluation of nuclear shape as currently
      practiced in routine preparations is improper because it is indirectly based on
      the distribution of DNA as revealed by the affinity for basic dyes. Therefore,
      over the last years we have been using as criteria morphological features of
      nuclei of thyroid and breast carcinomas as determined by immunofluorescence, in
      situ hybridization, and 3D reconstruction. We have translated this approach to
      routine diagnostic pathology on tissue sections by employing immunoperoxidase
      staining for emerin. Direct detection of nuclear envelope irregularities by
      tagging nuclear membrane proteins such as lamin B and emerin has resulted in a
      more objective definition of the shape of the nucleus. In this review we discuss
      in detail methodological issues as well as diagnostic and prognostic implications
      provided by decoration/staining of the nuclear envelope in both thyroid and
      breast cancer, thus demonstrating how much it matters "to be in the right shape"
      when dealing with pathological diagnosis of cancer. 

PMID- 24563346
TI  - RB and lamins in cell cycle regulation and aging.
AB  - While speculation has centered on a role for nuclear lamins in tumor progression
      for many years, most of the diseases that have been linked to lamin mutation are
      dystrophic in nature, often limiting the proliferation potential of affected
      cells in vivo and in vitro. Nevertheless, these lamin mutations, particularly in
      the LMNA gene that encodes A-type lamins, have provided an interesting tool set
      to understand functions of nuclear intermediate filament proteins in cell cycle
      progress and various means of exit, including quiescence, senescence, and
      differentiation down various lineages. The picture that has emerged is complex
      with lamins controlling the activity of key cell cycle factors such as the
      retinoblastoma protein (RB) and interacting with several important signal
      transduction pathways. Here we describe the current state of knowledge and
      speculate that lamins may be intimately involved in the regulation of cell
      proliferation, acting at the interface between cancer and aging. 

PMID- 24563348
TI  - NETs and cell cycle regulation.
AB  - There are many ways that the nuclear envelope can influence the cell cycle. In
      addition to roles of lamins in regulating the master cell cycle regulator pRb and
      nuclear envelope breakdown in mitosis, many other nuclear envelope proteins
      influence the cell cycle through regulatory or structural functions. Of
      particular note among these are the nuclear envelope transmembrane proteins
      (NETs) that appear to influence cell cycle regulation through multiple separate
      mechanisms. Some NETs and other nuclear envelope proteins accumulate on the
      mitotic spindle, suggesting functional or structural roles in the cell cycle. In
      interphase exogenous overexpression of some NETs promotes an increase in G1
      populations, while others promote an increase in G2/M populations, sometimes
      associated with the induction of senescence. Intriguingly, most of the NETs
      linked to the cell cycle are highly restricted in their tissue expression; thus,
      their misregulation in cancer could contribute to the many tissue-specific types
      of cancer. 

PMID- 24563349
TI  - Nuclear envelope regulation of signaling cascades.
AB  - The ultimate purpose of signal transduction is to transmit extracellular or
      cytoplasmic stimuli to the nuclear interior to elicit a cellular response,
      mediated primarily through changes in gene expression. The evolution of the
      nuclear envelope and the consequent compartmentalization of the genome, which is
      a defining feature of eukaryotes, introduced a physical barrier to the free
      access of genes. Initially regarded as nothing more than this, a physical barrier
      with selective permeability, recent findings have transformed our view of the
      nuclear envelope and its diverse roles in various aspects of cell biology and
      human diseases, much of which is only beginning to be understood. The realization
      that mutations in genes encoding nuclear envelope proteins cause a diverse array
      of tissue-selective diseases often referred to as "laminopathies" has provided
      new insight into structural and regulatory functions of the nuclear envelope.
      Genetic mutations causing abnormalities in the nuclear envelope can lead to
      dysregulated signaling that underlies pathogenesis of these diseases. The
      emerging picture indicates that the nuclear envelope is a node that fine-tunes
      signaling output and as such it may play a role in the biology of cancer. 

PMID- 24563350
TI  - Nuclear envelope: connecting structural genome organization to regulation of gene
      expression.
AB  - For many years, the nuclear envelope was viewed as a passive barrier that
      separates the genetic material in the nucleus from the cytoplasm of the cell and
      permits regulated trafficking of various molecules through the nuclear pores.
      Research in the past two decades has shown that the nuclear envelope is a complex
      cellular compartment, which harbors tissue-specific resident proteins,
      extensively interacts with chromatin and contributes to spatial genome
      organization and regulation of gene expression. Chromatin at the nuclear
      periphery is organized into active and silenced domains punctuated by insulator
      elements. The nuclear envelope transmembrane proteins and the nuclear lamina
      serve as anchoring sites for heterochromatin. They recruit chromatin that has
      been modified with specific epigenetic marks, provide silencing factors that add
      new epigenetic modifications to genes located at the nuclear periphery, and
      sequester transcription factors away from the nuclear interior. On the other
      hand, proteins of the nuclear pores anchor as well as help generate active
      chromatin, promote transcription, and coordinate gene expression with mRNA
      export. The importance of these functions is underscored by aberrant distribution
      of peripheral chromatin and changes in gene expression that occur in cancer and
      heritable human diseases linked to mutations in nuclear envelope proteins.
      Although many mechanistic questions addressing the role of the nuclear envelope
      in genome organization and function have been answered in recent years, a great
      deal remains to be discovered in this exciting and rapidly moving field. 

PMID- 24563347
TI  - Lamina-associated polypeptide (LAP)2alpha and other LEM proteins in cancer
      biology.
AB  - The LEM proteins comprise a heterogeneous family of chromatin-associated proteins
      that share the LEM domain, a structural motif mediating interaction with the DNA
      associated protein, Barrier-to-Autointegration Factor (BAF). Most of the LEM
      proteins are integral proteins of the inner nuclear membrane and associate with
      the nuclear lamina, a structural scaffold of lamin intermediate filament proteins
      at the nuclear periphery, which is involved in nuclear mechanical functions and
      (hetero-)chromatin organization. A few LEM proteins, such as Lamina-associated
      polypeptide (LAP)2alpha and Ankyrin and LEM domain-containing protein (Ankle)1
      lack transmembrane domains and localize throughout the nucleoplasm and cytoplasm,
      respectively. LAP2alpha has been reported to regulate cell proliferation by
      affecting the activity of retinoblastoma protein in tissue progenitor cells and
      numerous studies showed upregulation of LAP2alpha in cancer. Ankle1 is a nuclease
      likely involved in DNA damage repair pathways and single nucleotide polymorphisms
      in the Ankle1 gene have been linked to increased breast and ovarian cancer risk.
      In this review we describe potential mechanisms of the involvement of LEM
      proteins, particularly of LAP2alpha and Ankle1 in tumorigenesis and we provide
      evidence that LAP2alpha expression may be a valuable diagnostic and prognostic
      marker for tumor analyses. 

PMID- 24563351
TI  - Studying lamins in invertebrate models.
AB  - Lamins are nuclear intermediate filament proteins that are conserved in all
      multicellular animals. Proteins that resemble lamins are also found in
      unicellular organisms and in plants. Lamins form a proteinaceous meshwork that
      outlines the nucleoplasmic side of the inner nuclear membrane, while a small
      fraction of lamin molecules is also present in the nucleoplasm. They provide
      structural support for the nucleus and help regulate many other nuclear
      activities. Much of our knowledge on the function of nuclear lamins and their
      associated proteins comes from studies in invertebrate organisms and specifically
      in the nematode Caenorhabditis elegans and the fruit fly Drosophila melanogaster.
      The simpler lamin system and the powerful genetic tools offered by these model
      organisms greatly promote such studies. Here we provide an overview of recent
      advances in the biology of invertebrate nuclear lamins, with special emphasis on
      their assembly, cellular functions and as models for studying the molecular basis
      underlying the pathology of human heritable diseases caused by mutations in
      lamins A/C. 

PMID- 24563352
TI  - The non-random repositioning of whole chromosomes and individual gene loci in
      interphase nuclei and its relevance in disease, infection, aging, and cancer.
AB  - The genomes of a wide range of different organisms are non-randomly organized
      within interphase nuclei. Chromosomes and genes can be moved rapidly, with
      direction, to new non-random locations within nuclei upon a stimulus such as a
      signal to initiate differentiation, quiescence or senescence, or also the
      application of heat or an infection with a pathogen. It is now becoming
      increasingly obvious that chromosome and gene position can be altered in diseases
      such as cancer and other syndromes that are affected by changes to nuclear
      architecture such as the laminopathies. This repositioning seems to affect gene
      expression in these cells and may play a role in progression of the disease. We
      have some evidence in breast cancer cells and in the premature aging disease
      Hutchinson-Gilford Progeria that an aberrant nuclear envelope may lead to genome
      repositioning and correction of these nuclear envelope defects can restore proper
      gene positioning and expression in both disease situations.Although spatial
      positioning of the genome probably does not entirely control expression of genes,
      it appears that spatio-epigenetics may enhance the control over gene expression
      globally and/or is deeply involved in regulating specific sets of genes. A
      deviation from normal spatial positioning of the genome for a particular cell
      type could lead to changes that affect the future health of the cell or even an
      individual. 

PMID- 24563353
TI  - Cancer and the nuclear pore complex.
AB  - The nuclear pore complex (NPC) mediates trafficking between the cytoplasm and
      nucleoplasm. It also plays key roles in other nuclear processes such as chromatin
      silencing, transcriptional regulation, and DNA damage repair. Nucleoporins, the
      structural components of the NPC, have been linked to a multitude of cancers
      through chromosomal translocations generating fusion proteins, changes in protein
      expression levels, and single point mutations. Only a small number of
      nucleoporins have been linked to tumorigenesis thus far, and these proteins-
      Nup62, Nup88, Nup98, Nup214, Nup358/RanBP2, and Tpr--line the trafficking pathway
      and are particularly associated with mRNA export. Overexpression of several
      associated nuclear export factors, most also involved in various stages of mRNA
      export, has been linked to cancers as well. Some oncogenic nucleoporin mutants
      are mislocalized to either the cytoplasm or nucleoplasm while others are
      incorporated into the NPC, and in all these cases they are thought to misregulate
      signaling pathways and transcription through either altered or diminished
      nucleoporin functionality. Intriguingly, many viruses target the same cancer
      linked nucleoporins, often causing their degradation or mislocalization, implying
      that these viruses exploit some of the same weaknesses as the oncogenic defects.

PMID- 24563354
TI  - Roles of the nucleoporin Tpr in cancer and aging.
AB  - Tpr is a prominent architectural component of the nuclear pore complex that forms
      the basket-like structure on the nucleoplasmic side of the pore. Tpr, which
      stands for translocated promoter region, was originally described in the context
      of oncogenic fusions with the receptor tyrosine kinases Met, TRK, and Raf. Tpr
      has been since implicated in a variety of nuclear functions, including nuclear
      transport, chromatin organization, regulation of transcription, and mitosis. More
      recently, Tpr function has been linked to events including p53 signaling and
      premature aging in Hutchinson-Gilford Progeria Syndrome (HGPS). Here we provide
      an overview of the various processes that involve Tpr, and discuss how the levels
      and localization of a single protein can affect diverse pathways in the cell. 

PMID- 24563355
TI  - Ran GTPase in nuclear envelope formation and cancer metastasis.
AB  - Ran is a small ras-related GTPase that controls the nucleocytoplasmic exchange of
      macromolecules across the nuclear envelope. It binds to chromatin early during
      nuclear formation and has important roles during the eukaryotic cell cycle, where
      it regulates mitotic spindle assembly, nuclear envelope formation and cell cycle
      checkpoint control. Like other GTPases, Ran relies on the cycling between GTP
      bound and GDP-bound conformations to interact with effector proteins and regulate
      these processes. In nucleocytoplasmic transport, Ran shuttles across the nuclear
      envelope through nuclear pores. It is concentrated in the nucleus by an active
      import mechanism where it generates a high concentration of RanGTP by nucleotide
      exchange. It controls the assembly and disassembly of a range of complexes that
      are formed between Ran-binding proteins and cellular cargo to maintain rapid
      nuclear transport. Ran also has been identified as an essential protein in
      nuclear envelope formation in eukaryotes. This mechanism is dependent on importin
      beta, which regulates the assembly of further complexes important in this
      process, such as Nup107-Nup160. A strong body of evidence is emerging implicating
      Ran as a key protein in the metastatic progression of cancer. Ran is
      overexpressed in a range of tumors, such as breast and renal, and these perturbed
      levels are associated with local invasion, metastasis and reduced patient
      survival. Furthermore, tumors with oncogenic KRAS or PIK3CA mutations are
      addicted to Ran expression, which yields exciting future therapeutic
      opportunities. 

PMID- 24563356
TI  - Wnt signaling proteins associate with the nuclear pore complex: implications for
      cancer.
AB  - Several components of the Wnt signaling pathway have in recent years been linked
      to the nuclear pore complex. beta-catenin, the primary transducer of Wnt signals
      from the plasma membrane to the nucleus, has been shown to transiently associate
      with different FG-repeat containing nucleoporins (Nups) and to translocate
      bidirectionally through pores of the nuclear envelope in a manner independent of
      classical transport receptors and the Ran GTPase. Two key regulators of beta
      catenin, IQGAP1 and APC, have also been reported to bind specific Nups or to
      locate at the nuclear pore complex. The interaction between these Wnt signaling
      proteins and different Nups may have functional implications beyond nuclear
      transport in cellular processes that include mitotic regulation, centrosome
      positioning and cell migration, nuclear envelope assembly/disassembly, and the
      DNA replication checkpoint. The broad implications of interactions between Wnt
      signaling proteins and Nups will be discussed in the context of cancer. 

PMID- 24563358
TI  - Repo-man at the intersection of chromatin remodelling, DNA repair, nuclear
      envelope organization, and cancer progression.
AB  - Nuclear structure and chromatin changes are very useful biomarkers in cancer
      diagnosis. Despite this, their biological significance and relevance to cancer
      progression are still not well understood. The identification of new proteins
      that link the nuclear envelope to chromatin organization and the understanding of
      the molecular mechanisms underlying these connections have begun to provide some
      important clues. This review discusses the role of the nuclear protein Repo-Man
      (CDCA2) in the maintenance of genome stability. Repo-Man (CDCA2) is a targeting
      subunit for the protein phosphatase 1 involved in the dephosphorylation of
      histone H3 during mitotic exit. In this role, it is important for the chromatin
      organization in post-mitotic nuclei. Repo-Man (CDCA2) is also essential for
      proper nuclear envelope reformation and the regulation of DNA damage responses.
      The relevance of this complex for cancer biology is also corroborated by emerging
      evidence that provides a correlation between Repo-Man (CDCA2) expression levels
      and cancer progression; several studies now suggest that Repo-Man (CDCA2)
      represents a very strong prognostic marker for poor patient survival. 

PMID- 24563357
TI  - DNA damage and lamins.
AB  - The spatial and temporal organization of the genome has emerged as an additional
      level of regulation of nuclear functions. Structural proteins associated with the
      nuclear envelope play important roles in the organization of the genome. The
      nuclear lamina, a polymeric meshwork formed by lamins (A- and B-type) and lamin
      associated proteins, is viewed as a scaffold for tethering chromatin and protein
      complexes regulating a variety of nuclear functions. Alterations in lamins
      function impact DNA transactions such as transcription, replication, and repair,
      as well as epigenetic modifications that change chromatin structure. These data,
      and the association of defective lamins with a whole variety of degenerative
      disorders, premature aging syndromes, and cancer, provide evidence for these
      proteins operating as caretakers of the genome. In this chapter, we summarize
      current knowledge about the function of lamins in the maintenance of genome
      integrity, with special emphasis on the role of A-type lamins in the maintenance
      of telomere homeostasis and mechanisms of DNA damage repair. These findings have
      begun to shed some light onto molecular mechanisms by which alterations in A-type
      lamins induce genomic instability and contribute to the pathophysiology of aging
      and aging-related diseases, especially cancer. 

PMID- 24563359
TI  - Nuclear lamins and oxidative stress in cell proliferation and longevity.
AB  - In mammalian cells, the nuclear lamina is composed of a complex fibrillar network
      associated with the inner membrane of the nuclear envelope. The lamina provides
      mechanical support for the nucleus and functions as the major determinant of its
      size and shape. At its innermost aspect it associates with peripheral components
      of chromatin and thereby contributes to the organization of interphase
      chromosomes. The A- and B-type lamins are the major structural components of the
      lamina, and numerous mutations in the A-type lamin gene have been shown to cause
      many types of human diseases collectively known as the laminopathies. These
      mutations have also been shown to cause a disruption in the normal interactions
      between the A and B lamin networks. The impact of these mutations on nuclear
      functions is related to the roles of lamins in regulating various essential
      processes including DNA synthesis and damage repair, transcription and the
      regulation of genes involved in the response to oxidative stress. The major cause
      of oxidative stress is the production of reactive oxygen species (ROS), which is
      critically important for cell proliferation and longevity. Moderate increases in
      ROS act to initiate signaling pathways involved in cell proliferation and
      differentiation, whereas excessive increases in ROS cause oxidative stress, which
      in turn induces cell death and/or senescence. In this review, we cover current
      findings about the role of lamins in regulating cell proliferation and longevity
      through oxidative stress responses and ROS signaling pathways. We also speculate
      on the involvement of lamins in tumor cell proliferation through the control of
      ROS metabolism. 

PMID- 24563362
TI  - Nesprins in cell stability and migration.
AB  - Nesprins are a family of proteins that are primarily known for their localization
      along the nuclear envelope. Together with inner nuclear membrane SUN proteins,
      they form the core of the LINC (Linker of Nucleoskeleton and Cytoskeleton)
      complex that traverses both nuclear membranes to connect the cytoplasm and the
      nuclear interior. Based on their structure and interactions, Nesprins integrate
      the nucleus into the cytoskeleton of a cell. Mutations in Nesprins have been
      identified in a group of human diseases that have been summarized as
      laminopathies. Cellular functions of the Nesprins and recent studies on different
      cancer types additionally draw interest on Nesprins in the field of cancer
      research. Here we summarize recent findings about the structural arrangements of
      Nesprins along the nuclear envelope, and highlight Nesprin functions in basic
      cellular processes like maintenance of nuclear shape and size, and of nuclear and
      cellular or cytoskeletal organization, centrosomal positioning, cell migration,
      and signal transduction. In summary, Nesprins are involved in critical cellular
      processes, which in case of malfunction contribute to the formation of cancer and
      might represent novel targets in cancer diagnosis or for therapeutic
      intervention. 

PMID- 24563363
TI  - Connecting the nucleus to the cytoskeleton for nuclear positioning and cell
      migration.
AB  - The position of the nucleus in the cytoplasm is a highly regulated process and is
      required for multiple cellular and developmental processes. Defects on different
      nuclear positioning events are associated with several pathologies such as muscle
      and nervous system disorders. In this chapter we describe the current knowledge
      on the mechanism of nuclear positioning. We discuss how the nucleus connects to
      the cytoskeleton by nesprins and SUN proteins, how this connection is regulated
      by Samp1, and how this connection is required for proper nuclear positioning.
      Furthermore, we discuss how nesprins, SUN, and Samp1 form transmembrane actin
      associated nuclear (TAN) lines, novel nuclear envelope structures involved in
      force transduction during nuclear movement. Finally, we describe the recent
      evidences suggesting a role for the connection between the nucleus and the
      cytoskeleton in cancer. 

PMID- 24563364
TI  - Nuclear envelope invaginations and cancer.
AB  - The nuclear envelope (NE) surrounds the nucleus and separates it from the
      cytoplasm. The NE is not a passive structural component, but rather contributes
      to various cellular processes such as genome organization, transcription,
      signaling, and stress responses. Although the NE is mostly a smooth surface, it
      also forms invaginations that can reach deep into the nucleoplasm and may even
      traverse the nucleus completely. Cancer cells are generally characterized by
      irregularities and invaginations of the NE that are of diagnostic and prognostic
      significance. In the current chapter, we describe the link between nuclear
      invaginations and irregularities with cancer and explore possible mechanistic
      roles they might have in tumorigenesis. 

PMID- 24563361
TI  - Nuclear envelope in nuclear positioning and cell migration.
AB  - Hauling and anchoring the nucleus within immobile or motile cells, tissues,
      and/or syncytia represents a major challenge. In the past 15 years, Linkers of
      the Nucleoskeleton to the Cytoskeleton (LINC complexes) have emerged as
      evolutionary-conserved molecular devices that span the nuclear envelope and
      provide interacting interfaces for cytoskeletal networks and molecular motors to
      the nuclear envelope. Here, we review the molecular composition of LINC complexes
      and focus on how their genetic alteration in vivo has provided a wealth of
      information related to the relevance of nuclear positioning during tissue
      development and homeostasis with a special emphasis on the central nervous
      system. As it may be relevant for metastasis in a range of cancers, the
      involvement of LINC complexes in migration of nonneuronal cells via its
      interaction with the perinuclear actin cap will also be developed. 

PMID- 24563365
TI  - Mechanisms of nuclear size regulation in model systems and cancer.
AB  - Changes in nuclear size have long been used by cytopathologists as an important
      parameter to diagnose, stage, and prognose many cancers. Mechanisms underlying
      these changes and functional links between nuclear size and malignancy are
      largely unknown. Understanding mechanisms of nuclear size regulation and the
      physiological significance of proper nuclear size control will inform the
      interplay between altered nuclear size and oncogenesis. In this chapter we review
      what is known about molecular mechanisms of nuclear size control based on
      research in model experimental systems including yeast, Xenopus, Tetrahymena,
      Drosophila, plants, mice, and mammalian cell culture. We discuss how nuclear size
      is influenced by DNA ploidy, nuclear structural components, cytoplasmic factors
      and nucleocytoplasmic transport, the cytoskeleton, and the extracellular matrix.
      Based on these mechanistic insights, we speculate about how nuclear size might
      impact cell physiology and whether altered nuclear size could contribute to
      cancer development and progression. We end with some outstanding questions about
      mechanisms and functions of nuclear size regulation. 

PMID- 24563366
TI  - Control of nuclear size by NPC proteins.
AB  - The architecture of the cell nucleus in cancer cells is often altered in a manner
      associated with the tumor type and aggressiveness. Therefore, it has been the
      central criterion in the pathological diagnosis and prognosis of cancer. However,
      the molecular mechanism behind these observed changes in nuclear morphology,
      including size, remains completely unknown. Based on our current understanding of
      the physiology of the nuclear pore complex (NPC) and its constituents, which are
      collectively referred to as nucleoporins (Nups), we discuss how the structural
      and functional ablation of the NPC and Nups could directly or indirectly
      contribute to the changes in nuclear size observed in cancer cells. 

PMID- 24563367
TI  - Do lamins influence disease progression in cancer?
AB  - For nearly 60 years, diagnosis of cancer has been based on pathological tests
      that look for enlargement and distortion of nuclear shape. Because of their
      involvement in supporting nuclear architecture, it has been postulated that the
      basis for nuclear shape changes during cancer progression is altered expression
      of nuclear lamins and in particular lamins A and C. However, studies on lamin
      expression patterns in a range of different cancers have generated equivocal and
      apparently contradictory results. This might have been anticipated since cancers
      are diverse and complex diseases. Moreover, whilst altered epigenetic control
      over gene expression is a feature of many cancers, this level of control cannot
      be considered in isolation. Here I have reviewed those studies relating to
      altered expression of lamins in cancers and argue that consideration of changes
      in the expression of individual lamins cannot be considered in isolation but only
      in the context of an understanding of their functions in transformed cells. 

PMID- 24563360
TI  - Nuclear mechanics in cancer.
AB  - Despite decades of research, cancer metastasis remains an incompletely understood
      process that is as complex as it is devastating. In recent years, there has been
      an increasing push to investigate the biomechanical aspects of tumorigenesis,
      complementing the research on genetic and biochemical changes. In contrast to the
      high genetic variability encountered in cancer cells, almost all metastatic cells
      are subject to the same physical constraints as they leave the primary tumor,
      invade surrounding tissues, transit through the circulatory system, and finally
      infiltrate new tissues. Advances in live cell imaging and other biophysical
      techniques, including measurements of subcellular mechanics, have yielded
      stunning new insights into the physics of cancer cells. While much of this
      research has been focused on the mechanics of the cytoskeleton and the cellular
      microenvironment, it is now emerging that the mechanical properties of the cell
      nucleus and its connection to the cytoskeleton may play a major role in cancer
      metastasis, as deformation of the large and stiff nucleus presents a substantial
      obstacle during the passage through the dense interstitial space and narrow
      capillaries. Here, we present an overview of the molecular components that govern
      the mechanical properties of the nucleus, and we discuss how changes in nuclear
      structure and composition observed in many cancers can modulate nuclear mechanics
      and promote metastatic processes. Improved insights into this interplay between
      nuclear mechanics and metastatic progression may have powerful implications in
      cancer diagnostics and therapy and may reveal novel therapeutic targets for
      pharmacological inhibition of cancer cell invasion. 

PMID- 24563368
TI  - Heavy metal concentrations in Mullus barbatus and Pagellus erythrinus in relation
      to body size, gender, and seasonality.
AB  - Marine environments have been subjected to an increase in heavy metal pollution.
      Investigations were conducted in the bioaccumulation of heavy metals for both a
      benthic (Mullus barbatus) and a benthopelagic fish species (Pagellus erythrinus).
      The aim of this study was to examine the concentration levels of four metals in
      the body tissue of two fish species, in Pagasitikos Gulf in Greece, and to
      determine if metal concentration levels were affected by season, size, and
      species. Fish samples were collected monthly from September 2009 to August 2010.
      Chromium (Cr), Copper (Cu), Zinc (Zn), and Cadmium (Cd) concentrations were
      measured in muscle, gills, vertebral column, and in the "remaining fish sample."
      Statistical analysis pinpointed substantial differences in metal concentration
      levels between some size classes. Significant differences were observed between
      two fish species' tissues concerning Cu, Zn, and Cd concentrations. Cu and Zn
      concentrations varied amongst red mullet tissues as did Zn and Cd concentrations
      in common pandora. Ample variations were found seasonally in metal concentration
      levels; however, nonsignificant statistical differences were found among sexes. 

PMID- 24563369
TI  - My Body is a Temple: Eating Disturbances, Religious Involvement, and Mental
      Health Among Young Adult Women.
AB  - A growing body of the literature outlines the undesirable mental health
      consequences of eating disturbances. However, little attention has been given to
      the possible mitigating effects of cultural institutions, such as religion, in
      the lives of women suffering from such pathologies. Our work contributes to the
      literature by (a) outlining a series of arguments linking eating disturbances,
      religion, and mental health; (b) specifying two conceptual models of these
      relationships; and (c) testing relevant hypotheses using data on a large
      nationwide sample of young women. Results indicate that religious involvement
      organizational, non-organizational, and subjective religiousness-moderates the
      effects of eating disturbances on mental health, particularly for self-esteem.
      Study limitations are identified and several promising directions for future
      research are discussed. 

PMID- 24563370
TI  - Religiousness, religious coping with illness, and psychological function among
      Polish elderly patients with osteoarthritis undergoing arthroplasty.
AB  - To determine the influence of religious coping and religiousness on the
      psychological functioning of Polish patients before and after arthroplasty, a
      prospective study was performed. Out of a pool of 102 potential participants, a
      total of 61 (34 females, 27 males) completed a purposely created survey, Brief
      COPE followed by preoperative and postoperative Perceived Stress Scale, State
      Trait Anxiety Inventory and Satisfaction with Life Scale. Religious coping was
      not associated with: (1) perceived stress before or after surgery; (2)
      preoperative or postoperative anxiety; (3) life satisfaction. A two-factor ANOVA
      has shown that religious coping controlled by religiousness was related to better
      psychological functioning. Between- and within-subjects effects were observed for
      improvement in life satisfaction measured by split-plot ANOVA, which suggests (p
      < 0.05) that such improvement was greater among subjects of higher religious
      orientation. We concluded that religious strategies in dealing with stress
      measured by Brief-COPE were least likely to benefit patients of low-religious
      orientation. The study demonstrated the importance of core religious beliefs in
      predicting benefits derived from religiousness in the face of a crisis. This
      study showed that regardless of its effectiveness, turning to religion is common
      among Polish patients about to undergo surgery for osteoarthritis of the hip.

PMID- 24563372
TI  - Difficulties of motion-onset VEP interpretation in school-age children.
AB  - BACKGROUND: In adults, motion-onset visual evoked potentials (M-VEPs) with a
      dominant N2 peak represent a useful diagnostic tool. However, it is difficult to
      use this type of VEP in children because of the long maturation (up to 18 years)
      of M-VEPs, which is characterised by a gradual decrease in N2 peak latency and
      shape development. Moreover, in some children, M-VEPs are difficult to identify
      with standard stimuli. METHODS: We tested features of M-VEPs in 30 children (7-12
      years) with the following set of standard stimuli used in our lab for examining
      adults ( https://web.lfhk.cuni.cz/elf ): low-contrast translation motion (TM) and
      expansion/contraction motion (ExCoM) in full field and in periphery (with central
      20 degrees  masked). In 16 children, a high-contrast TM was also tested. RESULTS:
      With standard (low-contrast) stimuli, a common M-VEP to TM and to ExCoM was
      detected in 77 and 83 % of children, respectively. The M-VEPs to ExCoM in the
      periphery were detected in only 43 % of children. An abnormal dominant P1 peak
      was found in 9 % of VEPs to TM, 12 % of VEPs to full-field ExCoM and 14 % of VEPs
      to peripheral ExCoM. The M-VEPs to all low-contrast stimuli displayed large inter
      individual latency variability (N2 peak latency differed for more than 100 ms).
      High contrast (more suitable for the non-mature magnocellular pathway) shortened
      M-VEP latencies and improved amplitudes. CONCLUSIONS: Our findings show that the
      maturation of motion perception in children is inter-individually variable, which
      limits the diagnostic use of M-VEPs.

PMID- 24563371
TI  - NORE1A sensitises cancer cells to sorafenib-induced apoptosis and indicates
      hepatocellular carcinoma prognosis.
AB  - NORE1A, identified as a Ras effector, is frequently silenced in human cancers and
      has been implicated in tumour progression. Reports showing that NORE1A may
      function as a tumour suppressor have been emerging. However, to date, its
      expression and relevant significance in hepatocellular carcinoma (HCC) remain
      elusive. In this study, we examined the expression of NORE1A in HCC cell lines
      and a cohort of 250 HCC samples. We found that both the mRNA and the protein
      levels of NORE1A were noticeably downregulated in 14 fresh HCC tissues, compared
      to corresponding paracarcinoma tissues. Furthermore, NORE1A in tumours was
      decreased in 72.4% (181/250) of HCC patients. Low NORE1A expression was
      significantly associated with poor differentiation (P = 0.003), advanced stage (P
      = 0.002), high level of serum AFP (P < 0.001), vascular invasion (P = 0.034) and
      incomplete involucrum (P = 0.018). Multivariate analysis revealed that NORE1A was
      an independent poor prognostic factor for both overall survival (hazard ratio
      (HR) 0.622, 95% confidence interval (95% CI) 0.405-0.956, P = 0.030) and
      recurrence-free survival (HR 0.613, 95% CI 0.390-0.964, P = 0.034). Moreover, low
      NORE1A expression in advanced-stage HCC predicted disease relapse. In addition,
      NORE1A overexpression reduced cell viability, inhibited colony formation, and
      attenuated cell invasion in vitro. Further study demonstrated that NORE1A was
      capable of sensitising cancer cells to sorafenib-induced apoptosis via the
      activation of the Mst-1/Akt pathway. Collectively, our data suggest that NORE1A
      may be a promising prognostic biomarker and therapeutic target in HCC.

PMID- 24563373
TI  - High-sensitivity cardiac troponin I detection for 2 types of drug-induced
      cardiotoxicity in patients with breast cancer.
AB  - BACKGROUND: Breast cancer treatment with trastuzumab, a monoclonal antibody that
      targets human epidermal growth factor receptor type 2 (HER2), has largely been
      successful in improving the prognosis of HER2-positive disease. However, a
      critical issue associated with trastuzumab treatment is its cardiotoxic adverse
      effects, including cardiac insufficiency. METHODS: We measured levels of cardiac
      troponin I, a marker of myocardial damage, with a highly sensitive method (hs
      cTnI) using a fully automated chemiluminescent immunoassay system (ADVIA
      Centaur((r)) XP) in breast cancer patients and examined the relationship between
      administration of trastuzumab and epirubicin and concentrations of hs-cTnI.
      RESULTS: The coefficient of variation for within-run repeatability was 1.34-5.93
      %, using plasma pools and controls of 3 concentrations, and that for between-run
      reproducibility was 3.99-8.79 %, indicating high precision of the assay. In a
      dilutional linearity test with highly concentrated specimens, hs-cTnI values
      could be measured up to 50 ng/mL with linearity. No influence from coexisting
      substances was observed. The concentration of hs-cTnI was at or above the
      reference range (0.04 ng/mL) in 9 of 214 total breast cancer cases (4.2 %). The
      hs-cTnI concentration was at or above the reference range in 4 of 49 cases (8.2
      %) that were administered trastuzumab, and in 5 of 165 cases (3.0 %) that were
      not. Trastuzumab did not cause elevation of hs-cTnI when not administered in
      combination with epirubicin. CONCLUSIONS: These results suggest that epirubicin
      and trastuzumab cause cardiotoxicity through different mechanisms. Epirubicin can
      cause myocardial necrosis, while trastuzumab can cause cardiomyopathy without
      myocardial necrosis.

PMID- 24563374
TI  - Beneficial and cautionary outcomes of resveratrol supplementation in pregnant
      nonhuman primates.
AB  - Resveratrol has been proposed as a potential therapeutic to improve metabolic
      health during pregnancy, yet little is known about the fetal effects of this
      maternal dietary supplement. We hypothesized that when administered to pregnant
      nonhuman primates (NHPs), resveratrol would increase uterine blood flow and
      mitigate the harmful consequences of maternal Western-style diet (WSD)
      consumption. NHPs were fed a WSD (36% fat) supplemented with 0.37% resveratrol
      throughout pregnancy. Outcomes were compared with cohorts fed WSD alone and
      control chow (14% fat) to distinguish between WSD and resveratrol-specific
      effects in these animals. In the early third trimester, uterine blood flow was
      measured by Doppler ultrasound before fetal delivery and tissue collection.
      Resveratrol resulted in 30% maternal weight loss and improved glucose tolerance,
      increased uterine artery volume blood flow, and decreased placental inflammation
      and liver triglyceride deposition. In addition, fetal pancreatic mass was
      enlarged by 42%, with a 12-fold increase in proliferation by Ki67
      immunohistochemistry. These results demonstrate that resveratrol use during
      pregnancy yields improvements in maternal and placental phenotype with beneficial
      effects in the fetal liver but an unexplained and concerning alteration in fetal
      pancreatic development, which strongly cautions against the use of resveratrol by
      pregnant women.

PMID- 24563377
TI  - Clinician-trialist rounds: 21. The presenting complaints, diagnoses and
      treatments of mentorships in trouble. Part 1: Dysfunctional mentorship meetings.

PMID- 24563375
TI  - Systematic reviews to ascertain the safety of diabetes medications.
AB  - Clinicians and patients with type 2 diabetes enjoy an expanding list of
      medications to improve glycemic control. With this expansion has come a flurry of
      concerns about the safety of these antihyperglycemic agents, concerns that affect
      judgments about the risk/benefit balance of therapy. Some of these safety signals
      have been identified through the synthesis of existing research evidence. Thus,
      it has become important for clinicians and clinical policymakers to understand
      the strengths and limitations of systematic reviews and meta-analyses in
      determining the safety of diabetes medications. In this paper, we highlight key
      safety concerns with diabetes medications and discuss the role evidence synthesis
      plays in each, with special attention to its strengths and limitations. 

PMID- 24563376
TI  - Real-time PCR quantification of the plant growth promoting bacteria
      Herbaspirillum seropedicae strain SmR1 in maize roots.
AB  - The plant growth promoting bacteria Herbaspirillum seropedicae SmR1 is an
      endophytic diazotroph found in several economically important crops. Considering
      that methods to monitor the plant-bacteria interaction are required, our
      objective was to develop a real-time PCR method for quantification of PGPB H.
      seropedicae in the rhizosphere of maize seedlings. Primer pairs were designed,
      and their specificity was verified using DNA from 12 different bacterial species.
      Ten standard curves of qPCR assay using HERBAS1 primers and tenfold serial
      dilutions of H. seropedicae SmR1 DNA were performed, and PCR efficiency of 91 %
      and correlation coefficient of 0.99 were obtained. H. seropedicae SmR1 limit of
      detection was 10(1) copies (corresponding to 60.3 fg of bacterial DNA). qPCR
      assay using HERBAS1 was used to detect and quantify H. seropedicae strain SmR1 in
      inoculated maize roots, cultivated in vitro and in pots, harvested 1, 4, 7, and
      10 days after inoculation. The estimated bacterial DNA copy number per gram of
      root was in the range 10(7)-10(9) for plants grown in vitro and it was around
      10(6) for plants grown in pots. Primer pair HERBAS1 was able to quantify H.
      seropedicae SmR1, and this assay can be useful for monitoring plant-bacteria
      interaction.

PMID- 24563378
TI  - Sex differences in the acute nasal antioxidant/antielectrophilic response of the
      rat to inhaled naphthalene.
AB  - Naphthalene is a nasal carcinogen, inducing respiratory adenomas in male and
      olfactory neuroblastomas in female rats, respectively. The reasons for the site
      and sex-specific tumorigenic response are unknown. Naphthalene is bioactivated to
      electrophilic metabolites; cytotoxicity followed by regenerative cell
      proliferation is likely involved in the tumorigenic response. To examine sex
      differences in the acute nasal response to naphthalene, male and female F344 rats
      were nose-only exposed to 0, 1, 3, 10, or 30 ppm naphthalene vapor for 4 or 6 h.
      Following exposure, respiratory/transitional mucosa (RTM) and olfactory mucosa
      (OM) were isolated and analyzed for markers of oxidant/electrophilic stress
      and/or toxicity, including reduced/oxidized glutathione levels (GSH/GSSG), mRNA
      levels of electrophile-responsive genes, and epithelial cytoxicity (as measured
      by membrane permeability to ethidium homodimer-1). Naphthalene caused significant
      depletion of GSH in RTM and OM with no increase in GSSG. Cytotoxicity was
      apparent at concentrations of 15 and 30 ppm. No consistent sex differences were
      observed in these responses. Sex differences were observed in the induction of
      antielectrophilic genes in OM: glutamyl cysteine ligase (catalytic subunit)
      (Gclc), NADPH quinone oxidase 1 (Nqo1), and heme oxygenase 1 (Hmox1) were all
      induced to a greater extent in the male OM compared with the female. No
      consistent sex differences were observed in the RTM. Although the mechanism of
      the sex difference in the RTM adenoma response remains enigmatic, sex differences
      in the induction of antioxidant/electrophile-responsive genes may contribute to
      the heightened sensitivity of the female OM to the carcinogenic effects of
      naphthalene.

PMID- 24563380
TI  - Andrographolide sensitizes the cytotoxicity of human colorectal carcinoma cells
      toward cisplatin via enhancing apoptosis pathways in vitro and in vivo.
AB  - Andrographolide (Andro), a diterpenoid lactone isolated from a traditional herbal
      medicine Andrographis paniculata, has been shown to suppress the growth and
      invasion of human colorectal carcinoma (CRC) Lovo cells, and trigger apoptosis in
      vitro. The potential of Andro as a chemotherapeutic agent in CRC was evaluated by
      investigating its cytotoxic effects as a single agent or in coadministration with
      cisplatin (CDDP). Andro potentiated the cytotoxic effect of CDDP in Lovo cells
      through apoptosis. The molecular mechanism for these favorable cellular response
      was further investigated by analyzing the apoptotic profiles, protein levels, and
      mRNA expression patterns of several key genes after treatments of Andro or/and
      CDDP. Molecular results indicated that the effect of Andro alone might be
      mediated via both intrinsic and extrinsic apoptotic pathways in Lovo cells. The
      addition of Andro to CDDP induced synergistic apoptosis, which could be
      corroborated to the changes in protein and mRNA levels of Bax and Bcl-2, and the
      increased Fas/FasL association in these cells, resulting in increased release of
      cytochrome c, and activation of caspases. Pretreatment of Nok-1 monoclonal
      antibody, a Fas signaling inhibitor, or Bax inhibitor peptide V5 repressed the
      Andro-induced cleavage of procaspase and the sensitization to CDDP-induced
      apoptosis. Finally, the combination therapy of Andro with CDDP was evidenced by
      its synergistic inhibition on the growth of Lovo cells in xenograft tumor
      studies. The results indicate that Andro, in combination with chemotherapeutics,
      is likely to represent a potential therapeutic strategy for CRC. 

PMID- 24563381
TI  - Are structural analogues to bisphenol a safe alternatives?
AB  - BACKGROUND: Bisphenol A (BPA) is a chemical with widespread human exposure
      suspected of causing low-dose effects. Thus, a need for developing alternatives
      to BPA exists. Structural analogues of BPA have already been detected in foods
      and humans. Due to the structural analogy of the alternatives, there is a risk of
      effects similar to BPA. OBJECTIVES: The aim was to elucidate and compare the
      hazards of bisphenol B (BPB), bisphenol E (BPE), bisphenol F (BPF), bisphenol S
      (BPS) and 4-cumylphenol (HPP) to BPA. METHODS: In vitro studies on
      steroidogenesis, receptor activity, and biomarkers of effect, as well as
      Quantitative Structure-Activity Relationship (QSAR) modeling. RESULTS: All test
      compounds caused the same qualitative effects on estrogen receptor and androgen
      receptor activities, and most of the alternatives exhibited potencies within the
      same range as BPA. Hormone profiles for the compounds indicated a specific
      mechanism of action on steroidogenesis which generally lead to decreased
      androgen, and increased estrogen and progestagen levels. Differential effects on
      corticosteroid synthesis were observed suggesting a compound-specific mechanism.
      Overall, BPS was less estrogenic and antiandrogenic than BPA, but BPS showed the
      largest efficacy on 17alpha-hydroxyprogesterone (17alpha-OH progesterone).
      Finally, there were indications of DNA damage, carcinogenicity, oxidative stress,
      effects on metabolism, and skin sensitization of one or more of the test
      compounds. CONCLUSIONS: Interference with the endocrine system was the
      predominant effect of the test compounds. A substitution of BPA with these
      structural analogues should be carried out with caution.

PMID- 24563382
TI  - Response of Tribolium castaneum to elevated copper concentrations is influenced
      by history of metal exposure, sex-specific defences, and infection by the
      parasite Steinernema feltiae.
AB  - We studied how copper toxicity in the red flour beetle, Tribolium castaneum
      changed as a result of infection by the entomopathogenic nematode Steinernema
      feltiae. Measured traits were: respiration, growth and survival, as well as the
      concentrations of copper within beetle tissues and in its diet. By comparing F1
      and F5 generation we were able to answer how long-term metal exposure changed the
      responses to both copper and the parasite. The beetles did accumulate copper;
      however, the results indicated that copper concentrations in beetle tissues were
      affected by nematode infection, the sex of the experimental animals, and the
      number of generations of exposure. Five generations of exposure to copper
      resulted in the highest dry body mass of infected beetles of both sexes;
      additionally, this group also had the lowest copper concentrations in their
      tissues. The only factor that had a significant effect on respiration was
      infection by nematodes: infected beetles of both sexes in both generational
      groups had significantly decreased respiration rates. Survival was lowest in
      nematode-infected animals of both sexes from both generations, regardless of
      exposure to copper. Our results confirm that an organism's response to metal
      pollution is dependent on its health status and sex. We also found that the
      history of exposure to metal was equally important-we found enhanced resistance
      to copper intoxication after only five generations of exposure. 

PMID- 24563379
TI  - Identification of hepatic phospholipidosis inducers in sandwich-cultured rat
      hepatocytes, a physiologically relevant model, reveals altered basolateral uptake
      and biliary excretion of anionic probe substrates.
AB  - Drug-induced phospholipidosis (PLD) is characterized by phospholipid accumulation
      within the lysosomes of affected tissues, resulting in lysosomal enlargement and
      laminar body inclusions. Numerous adverse effects and toxicities have been linked
      to PLD-inducing drugs, but it remains unknown whether drug-induced PLD represents
      a distinct toxicity or cellular adaptation. In silico and immortalized cellular
      models have been used to evaluate the PLD potential of new drugs, but these
      systems have some limitations. The aims of this study were to determine whether
      primary sandwich-cultured hepatocytes (SCH) can serve as a sensitive and
      selective model to evaluate hepatic drug-induced PLD, and to evaluate the impact
      of PLD on the uptake and biliary excretion of probe substrates, taurocholate (TC)
      and rosuvastatin (RSV). Rat SCH were cultured for 48 h with prototypic hepatic
      PLD-inducing drugs, amiodarone (AMD), chloroquine (CHQ), desipramine (DES), and
      azithromycin (AZI), as well as the renal PLD inducer gentamicin (GTM).
      LysoTracker Red localization and transmission electron microscopy indicated
      enlarged lysosomal compartments and laminar body inclusions in SCH treated with
      AMD, CHQ, DES, and AZI, but not GTM, relative to control. PLD resulted in a 51
      92% decrease in the in vitro biliary clearance of both TC and RSV; the biliary
      excretion index significantly decreased for TC from 88 to 35-73%. These data
      suggested that PLD significantly reduced both organic anion transporting
      polypeptide-mediated uptake, and bile salt export pump-mediated biliary transport
      processes. The current study demonstrates that the rat SCH system is a promising
      model to study hepatic PLD in vitro. Altered hepatic transport of anionic
      substrates secondary to drug-induced PLD is a novel finding. 

PMID- 24563384
TI  - Cats in recent Chinese study on cat domestication are commensal, not
      domesticated.

PMID- 24563383
TI  - Surface shear inviscidity of soluble surfactants.
AB  - Foam and emulsion stability has long been believed to correlate with the surface
      shear viscosity of the surfactant used to stabilize them. Many subtleties arise
      in interpreting surface shear viscosity measurements, however, and correlations
      do not necessarily indicate causation. Using a sensitive technique designed to
      excite purely surface shear deformations, we make the most sensitive and precise
      measurements to date of the surface shear viscosity of a variety of soluble
      surfactants, focusing on SDS in particular. Our measurements reveal the surface
      shear viscosity of SDS to be below the sensitivity limit of our technique, giving
      an upper bound of order 0.01 MUN.s/m. This conflicts directly with almost all
      previous studies, which reported values up to 10(3)-10(4) times higher. Multiple
      control and complementary measurements confirm this result, including direct
      visualization of monolayer deformation, for SDS and a wide variety of soluble
      polymeric, ionic, and nonionic surfactants of high- and low-foaming character. No
      soluble, small-molecule surfactant was found to have a measurable surface shear
      viscosity, which seriously undermines most support for any correlation between
      foam stability and surface shear rheology of soluble surfactants. 

PMID- 24563385
TI  - Comparing two deep brain stimulation leads to one in refractory tremor.
AB  - A sizable proportion of medication refractory tremor patients may not respond
      satisfactorily to deep brain stimulation (DBS) to the ventralis intermedialis
      nucleus of the thalamus (Vim). Implanting a second DBS lead ipsilaterally to the
      first one is thought to be beneficial based on scarce and unblinded data. This
      article aims to report a double-blind assessment of five patients with a second
      DBS lead for refractory tremor. Tremor was assessed by two blinded movement
      disorder specialists using a videotaped tremor rating scale (TRS) evaluation of
      each patient in four conditions: both leads OFF, Vim ON/2nd lead OFF, Vim OFF/2nd
      lead ON, and both leads ON. Paired t-test was used to determine if double
      stimulation was different than stimulation of Vim alone or than stimulation of
      the 2nd lead alone. Each hypothesis was tested with the total TRS as well as the
      contralateral upper limb score and the contralateral hemibody score. Tremor was
      secondary to multiple sclerosis in two patients and to essential tremor in three.
      The second lead was in the ventralis oralis anterior nucleus of the thalamus in
      three patients and in the prelemniscal radiations in two patients. There was
      improvement with the 2nd lead or double ON in four patients compared to
      stimulating the Vim alone. However, when taken as a group, the results were not
      statistically significant. These results were constant with the three different
      ratings used. The lack of overall statistically significant improvement might be
      secondary to the small size and the heterogeneity of our sample. However, four
      patients had 17 to 60 % tremor improvement after the implant of the 2nd lead on
      double-blinded evaluation. We report objective improvement after addition of a
      second DBS lead in patients with tremor refractory to Vim DBS. Larger studies are
      needed to confirm these results.

PMID- 24563386
TI  - 4-hydroxyglutamate is a biomarker for primary hyperoxaluria type 3.
AB  - Primary hyperoxaluria type 3 (PH3) is a recently identified inborn error of 4
      hydroxyproline metabolism causing kidney stone disease. Diagnosis to date has
      relied on mutation detection. The excretion of 4-hydroxyglutamate (4OHGlu) was
      investigated in controls and a cohort of nine patients with PH3 and their parents
      using flow injection tandem mass spectrometry. 4OHGlu was stable in acidified
      urine samples and was not influenced by diet. Its measurement was readily
      incorporated into an existing multi-analyte panel for comprehensive screening for
      inborn errors of metabolism. There was a steady decline with age in 4OHGlu
      levels, expressed as MUmol/mmol of creatinine, in controls. Levels in patients
      with PH3 ranged from 6.5 to 98 MUmol/mmol of creatinine and were all
      significantly increased when compared to age-matched controls (<4.2). Levels in
      eight parents (obligatory carriers of the corresponding mutation) were
      moderately, but significantly increased, ranging from 0.6 to 2.5 (age-matched
      controls <1.4, p = 0.03). Urine 4OHGlu screening was used to prospectively
      diagnose PH3 in an 18-month-old boy with calcium oxalate kidney stone disease
      associated with hyperoxaluria. 4OHGlu was also increased in a stored newborn
      screening dried blood spot sample from this child (37 MUmol/L, controls <2.53).
      4OHGlu testing provides a robust and high-throughput biochemical screen for PH3. 

PMID- 24563387
TI  - Strong evidence against platelet-rich plasma injections for chronic lateral
      epicondylar tendinopathy: a systematic review.
AB  - BACKGROUND: Chronic lateral epicondylar tendinopathy is frequent in athletes, and
      platelet-rich plasma (PRP) is being used increasingly in its treatment.
      OBJECTIVE: To systematically review the literature on the efficacy of PRP
      injections for chronic lateral epicondylar tendinopathy. METHODS: The databases
      of PubMed, EMBASE, CINAHL, Medline OvidSP, Scopus, Google Scholar, Web of Science
      and Cochrane Library were searched in October 2013. Inclusion criteria were a
      clinical diagnosis of chronic lateral epicondylar tendinopathy, a randomised
      controlled trial, an intervention with a PRP injection and the outcome measures
      described in terms of pain and/or function. One author screened the search
      results and two authors independently assessed the study quality using the
      Physiotherapy Evidence Database (PEDro) score. A study was considered to be of
      high quality if its PEDro score was >=6. A best evidence synthesis was used to
      identify the level of evidence. RESULTS: 6 studies were included, of which four
      were considered to be of high quality. Three high-quality studies (75%) and two
      low-quality studies showed no significant benefit at the final follow-up
      measurement or predefined primary outcome score when compared with a control
      group. One high-quality study (25%) showed a beneficial effect of a PRP injection
      when compared with a corticosteroid injection (corticosteroid injections are
      harmful in tendinopathy). Based on the best evidence synthesis, there is strong
      evidence that PRP injections are not efficacious in chronic lateral epicondylar
      tendinopathy. CONCLUSIONS: There is strong evidence that PRP injections are not
      efficacious in the management of chronic lateral elbow tendinopathy.

PMID- 24563388
TI  - The LEAF questionnaire: a screening tool for the identification of female
      athletes at risk for the female athlete triad.
AB  - BACKGROUND: Low energy availability (EA) in female athletes with or without an
      eating disorder (ED) increases the risk of oligomenorrhoea/functional
      hypothalamic amenorrhoea and impaired bone health, a syndrome called the female
      athlete triad (Triad). There are validated psychometric instruments developed to
      detect disordered eating behaviour (DE), but no validated screening tool to
      detect persistent low EA and Triad conditions, with or without DE/ED, is
      available. AIM: The aim of this observational study was to develop and test a
      screening tool designed to identify female athletes at risk for the Triad.
      METHODS: Female athletes (n=84) with 18-39 years of age and training >=5
      times/week filled out the Low Energy Availability in Females Questionnaire (LEAF
      Q), which comprised questions regarding injuries and gastrointestinal and
      reproductive function. Reliability and internal consistency were evaluated in a
      subsample of female dancers and endurance athletes (n=37). Discriminant as well
      as concurrent validity was evaluated by testing self-reported data against
      measured current EA, menstrual function and bone health in endurance athletes
      from sports such as long distance running and triathlon (n=45). RESULTS: The 25
      item LEAF-Q produced an acceptable sensitivity (78%) and specificity (90%) in
      order to correctly classify current EA and/or reproductive function and/or bone
      health. CONCLUSIONS: The LEAF-Q is brief and easy to administer, and relevant as
      a complement to existing validated DE screening instruments, when screening
      female athletes at risk for the Triad, in order to enable early detection and
      intervention.

PMID- 24563389
TI  - Enhancing performance and sport injury prevention in disability sport: moving
      forwards in the field of football.

PMID- 24563390
TI  - Visual or computer-based measurements: important for interpretation of athletes'
      ECG.
AB  - BACKGROUND: ECG is recommended for preparticipation health examination in
      athletes. Owing to a lack of consensus on how to read and interpret athletes'
      ECGs, different criteria for abnormality are used. AIMS: To compare the
      prevalence of abnormal ECGs and test the correlation between visual and computer
      based measurements. METHODS: In a preparticipation cardiac screening examination
      of 595 male professional soccer players aged 18-38 years, ECGs were categorised
      according to the European Society of Cardiology's (ESC) recommendations and the
      Seattle criteria, respectively. Visual measurements were conducted with callipers
      on-screen on the averaged PQRST complex in each lead, calculated by the trimmed
      mean. Computer-based measurements were derived from the medium beat. Heart rhythm
      and conduction were scored visually by a cardiologist. Categorical variables were
      compared by kappa statistics (K) and continuous variables by intraclass
      correlation. RESULTS: ECGs of good quality were available from 579 players.
      According to the ESC's recommendations and Seattle criteria, respectively, ECGs
      were categorised as abnormal in 171 (29.5%) vs 64 (11.1%) players after visual
      assessment, and in 293 (50.6%; K=0.395) vs 127 (21.9%; K=0.564) after computer
      based measurements. Intraclass correlation was very good for measurements of R
      and S wave amplitudes and moderate to very good for intervals. K was very good
      for pathological Q wave amplitudes and moderate for T wave inversions.
      CONCLUSIONS: Abnormal ECGs were more than twice as common after computer-based
      than after visual measurements. Such a difference will markedly influence the
      number of athletes who need further examinations. Reference values may need
      adjustments dependent on measurement methods.

PMID- 24563391
TI  - Anterior cruciate ligament injury alters preinjury lower extremity biomechanics
      in the injured and uninjured leg: the JUMP-ACL study.
AB  - BACKGROUND: Information as to how anterior cruciate ligament (ACL) injury and
      reconstructive surgery (ACLR) alter lower extremity biomechanics may improve
      rehabilitation and return to play guidelines, reducing the risk for repeat ACL
      injury. AIM: To compare lower extremity biomechanics before ACL injury and after
      subsequent ACLR for the injured and uninjured leg. METHODS: Baseline unilateral
      lower extremity biomechanics were collected on the dominant leg of participants
      without ACL injury when they entered the Joint Undertaking to Monitor and Prevent
      ACL (JUMP-ACL) study. Thirty-one participants with subsequent ACL injury,
      reconstructive surgery and full return to physical activity completed repeat,
      follow-up biomechanical testing, as did 39 uninjured, matched controls. Not all
      injured participants suffered injury to the dominant leg, requiring separation of
      those with ACL injury into two groups: ACLR-injured leg group (n=12) and ACLR
      uninjured leg group (n=19). We compared the landing biomechanics of these three
      groups (ACLR-injured leg, ACLR-uninjured leg, control) before ACL injury
      (baseline) with biomechanics after ACL injury, surgery and return to physical
      activity (follow-up). RESULTS: ACL injury and ACLR altered lower extremity
      biomechanics, as both ACLR groups demonstrated increases in frontal plane
      movement (increased hip adduction and knee valgus). The ACLR-injured leg group
      also exhibited decreased sagittal plane loading (decreased anterior tibial shear
      force, knee extension moment and hip flexion moment). No high-risk biomechanical
      changes were observed in control group participants. CONCLUSIONS: ACL injury and
      ACLR caused movement pattern alterations of the injured and uninjured leg that
      have previously shown to increase the risk for future non-contact ACL injury.

PMID- 24563392
TI  - First metatarsocuneiform joint mobility: radiographic, anatomic, and clinical
      characteristics of the articular surface.
AB  - BACKGROUND: The first metatarsocuneiform joint is involved in first ray
      biomechanics and related forefoot pathology. The purpose of this study was to
      evaluate the first metatarsocuneiform joint radiographic findings in relation to
      angular position of the radiographic beam, and to assess the joint mobility as it
      relates to the anatomic orientation of the facets on both radiographic imaging
      and gross anatomic dissection. METHODS: Thirty-nine cadaveric lower extremity
      limbs were stratified as normal, mild, moderate, or severe hallux valgus
      deformity. Mobility of the first metatarsocuneiform joint for each specimen was
      assessed using the Klaue device. The medial inclination angle (obliquity) of the
      first metatarsocuneiform joint was determined on both 10-degree and 20-degree
      anteroposterior radiographs. The lateral inclination angle of both the dorsal and
      plantar facets was determined on lateral radiographs. Each specimen was then
      dissected to directly inspect the metatarsocuneiform joint. RESULTS: The
      metatarsocuneiform joint mean height was 28.3 mm and the mean width was 13.1 mm.
      Twenty-three feet demonstrated a continuous cartilaginous surface, 15 feet
      demonstrated a bilobed cartilaginous surface, and 1 foot demonstrated completely
      separated facets. Dorsal facets were curved in 37 specimens and flat 2 specimens.
      Plantar facets were flat in 30 specimens and curved in 9 specimens. The medial
      inclination angle measured 15.8 degrees on the 10-degree radiograph and 2.6
      degrees on the 20-degree radiograph. We were unable to establish any correlations
      of metatarsocuneiform joint angles or facet contour with mobility measured by the
      Klaue device. CONCLUSIONS: The metatarsocuneiform joint has a height to width
      ratio of nearly 2:1. Continuous and bilobed facets are both very common anatomic
      variants. The contour of the dorsal facet was predominantly curved and the
      contour of the plantar facet was predominantly flat. First metatarsocuneiform
      joint mobility does not appear to be dependent on the contour of the facets or
      the degree of medial inclination of the joint. CLINICAL RELEVANCE: Anatomic and
      radiographic findings with regard to mobility of the first metatarsocuneiform
      joint may assist the surgeon in interpreting the joint's relationship to hallux
      valgus deformity and to aid in clinical decision making. Our findings suggest
      that radiographic interpretation of medial inclination is unreliable and should
      not be used to determine the appropriateness of specific operative procedures.

PMID- 24563393
TI  - Nuclear weapons tests and environmental consequences: a global perspective.
AB  - The beginning of the atomic age marked the outset of nuclear weapons testing,
      which is responsible for the radioactive contamination of a large number of sites
      worldwide. The paper aims to analyze nuclear weapons tests conducted in the
      second half of the twentieth century, highlighting the impact of radioactive
      pollution on the atmospheric, aquatic, and underground environments. Special
      attention was given to the concentration of main radioactive isotopes which were
      released, such as 14C, 137Cs, and 90Sr, generally stored in the atmosphere and
      marine environment. In addition, an attempt was made to trace the spatial
      delimitation of the most heavily contaminated sites worldwide, and to note the
      human exposure which has caused a significantly increased incidence of thyroidal
      cancer locally and regionally. The United States is one of the important examples
      of assessing the correlation between the increase in the thyroid cancer incidence
      rate and the continental-scale radioactive contamination with 131I, a radioactive
      isotope which was released in large amounts during the nuclear tests carried out
      in the main test site, Nevada.

PMID- 24563394
TI  - Occupational challenges of young adult patients with congenital heart disease.
AB  - BACKGROUND: Despite improved survival of adults with congenital heart disease
      (CHD), higher rates of unemployment and work-related problems are seen,
      especially among younger adults. This study was performed to gain insight into
      current barriers and facilitating experiences at work among young adult patients
      with CHD. METHODS: This qualitative study consisted of semi-structured face-to
      face interviews, based on a self-constructed model from several existing models,
      which were held among outpatients with CHD from a large tertiary referral centre.
      Verbatim transcribed audio-taped data were analysed using a directed model-based
      content analysis approach. RESULTS: Fifteen patients had been interviewed when
      data saturation was reached. Work was important for all participants. Several
      barriers and facilitating factors were identified. Barriers were mostly on
      physical aspects and lack of opportunities for recovery. Important facilitating
      factors were good relationships with colleagues and employer and having
      sufficient opportunities for recovery. Most of these factors are also seen among
      patients with other chronic diseases, but with a different priority. CONCLUSION:
      This is the first study that has identified qualitative factors at work of young
      adult CHD patients. Work is important to them. Challenges are dealing with the
      physical barriers and getting enough support from colleagues. Specific coaching
      or a tailored group intervention could thereby be helpful. Future research should
      aim at the aetiology of problems and identifying patients who would benefit most
      from specific coaching.

PMID- 24563395
TI  - [(Patient) satisfaction in focus].

PMID- 24563397
TI  - [Neuromonitoring in children - how deep does my patient sleep?].
AB  - The electroencephalogram (EEG) of wakefulness, sleep, and anaesthesia changes
      during childhood. Especially marked are the changes during the first year of
      life. In the second half of the first year, in most children EEG stages can be
      classified visually and automatically during anaesthesia which are similar to
      those observed in older children. In the first months of life, the EEG of
      anaesthesia is less differentiated, but it is still useful in patient monitoring
      during anaesthesia. 

PMID- 24563398
TI  - [Awake fiberoptic intubation - gold standard for the anticipated difficult
      airway].
AB  - Awake fiberoptic intubation seems to continually lose importance in recent years.
      Alternative options of airway management are coming more and more into the focus
      of clinical anaesthesia and are moreover advertised specifically for the
      difficult airway. The concern seems justified that this intubation technique -
      once the indisputed standard in the management of the anticipated difficult
      airway - is practised less and less so that especially younger colleagues can
      hardly gain routine practice. This article aims at counteracting this trend and
      particularly demonstrates a practical approach. Against this background the
      equipment is described and tips and tricks are given for execution. The main
      focus are safety aspects and the success factor of a good topical mucosal
      anaesthesia, which is of greater importance than a concomitant sedation.

PMID- 24563400
TI  - [Nutrition in intensive care medicine--how?].

PMID- 24563399
TI  - [Case report - Intraosseous infusion as an alternative solution in the therapy of
      septicaemia in an adult].
AB  - The intraosseous access can be more often found in the guidelines and
      recommendations of the medical societies when an peripheral or central venous
      catheter cannot be established. For the adult this can mostly be found for the
      cardiopulmonary resuscitation or the patient with major trauma. In pediatrics and
      neonatology it is a reliable solution for the child in septic shock. In our case
      a 36 year old presented with an endocarditis and tricuspid valve insufficiency
      III degrees  by known intravenous drug-abuse and septic shock. It was initially
      impossible to establish an adequate peripheral or central venous catheter. For
      this reason a humeral intraosseous access was established. After stabilizing
      circulatory function and volume replacement a central-venous catheter could be
      placed and the patient was successfully surgically sanified. We used the EZ
      IO((Vidacare Corporation, San Antonio/USA). Appropriate systems should
      extensively be available in the clinical setting.

PMID- 24563401
TI  - [Nutrition of intensive care patients - how to reach target parameters].
AB  - Nutrition of intensive care patients is often complex and challenging due to
      metabolic changes. For this reason nutritional support adapted to the metabolic
      state is of key importance to avoid hyper- or hypoalimentation and thus has
      direct impact on the prognosis. Target parameters might be beneficial to
      establish an adequate and differentiated nutritional strategy but thus far
      concerning single nutritional components evidence-based data are only available
      for adjusting blood glucose levels. Furthermore, an early enteral nutrition is of
      major prognostic importance. In practice a supplementary parenteral support is
      often required to provide adequate calorie supply. Monitoring of residual gastric
      volume as a tool to regulate an effective enteral nutrition might possibly become
      less important due to recent study data. 

PMID- 24563402
TI  - [Nutrition of the critically ill - is less more? How much energy for the ICU
      patient?].
AB  - Decreased nutritional intake or preexisting malnutrition is associated with
      increased morbidity and mortality during hospital stay. However nutritional
      support in particular for the ICU patient is not trivial. Hyperalimentation in
      the acute phase of critical illness but also hypoalimentation in the chronic and
      stable phase of illness has to be avoided. Ideally about 25 kcal/kg/d should be
      targeted over a few days during metabolic monitoring. Alternatively indirect
      calorimetry should be applied where available.

PMID- 24563403
TI  - [Update glutamine and antioxidants in critically ill patients].
AB  - Critical illness leads to oxidative stress and can induce or exacerbate nutrient
      deficiencies. This predisposes patients in the intensive care unit to impaired
      immune function and increased risk of developing infectious complications, organ
      dysfunction, and therefore worsens clinical outcome. Immune-modulating properties
      of specific nutrients such as glutamine and antioxidants may support the
      endogenous antioxidative system, improve immune and organ function and translate
      into better clinical outcome of the critically ill patient. The following article
      summarizes the rationale and provides an update on recent clinical studies with
      special focus on the use of glutamine and antioxidants in critically ill
      patients. It further provides recommendations for the clinical use of these
      substrates in this particular patient population. 

PMID- 24563405
TI  - [Not Available].

PMID- 24563404
TI  - [The successfully treated patients - are they the satisfied ones?].
AB  - The current scientific opinion on the success of a therapy is that patients
      having undergone a successful therapy are satisfied. However, in reality, it is
      possible that patients with poor living conditions are satisfied (well-being
      paradox) whereas patients treated successfully are not (dissonance). The higher
      the psychological distress, the more rare is the assumption that successful
      therapy is an equivalent of satisfaction. Satisfaction depends more on
      fulfillment of patient expectations and involvement of the physicians.

PMID- 24563408
TI  - Populational equilibrium through exosome-mediated Wnt signaling in tumor
      progression of diffuse large B-cell lymphoma.
AB  - Tumors are composed of phenotypically heterogeneous cell populations. The
      nongenomic mechanisms underlying transitions and interactions between cell
      populations are largely unknown. Here, we show that diffuse large B-cell
      lymphomas possess a self-organized infrastructure comprising side population (SP)
      and non-SP cells, where transitions between clonogenic states are modulated by
      exosome-mediated Wnt signaling. DNA methylation modulated SP-non-SP transitions
      and was correlated with the reciprocal expressions of Wnt signaling pathway
      agonist Wnt3a in SP cells and the antagonist secreted frizzled-related protein 4
      in non-SP cells. Lymphoma SP cells exhibited autonomous clonogenicity and
      exported Wnt3a via exosomes to neighboring cells, thus modulating population
      equilibrium in the tumor. 

PMID- 24563409
TI  - [Vitreomacular interface diseases: vitreomacular adhesion, traction, epiretinal
      membrane, and macular hole].

PMID- 24563410
TI  - Changes to GP funding could force 98 practices to close, BMA warns.

PMID- 24563411
TI  - Relationship between detector size and the need for extra images and their effect
      on radiation exposure in digital mammography screening.
AB  - PURPOSE: To determine the number of extra images (EI) that are necessary for
      imaging large breasts when using a detector smaller than 24 cm * 30 cm and to
      calculate the additional average glandular dose (AGD) for these images. MATERIALS
      AND METHODS: The screening mammograms taken between 2007 and 2011 were assessed
      for a photon counting full-field digital mammography (PCM) system (detector size:
      24 cm * 26 cm) and a computed radiography (CR) system (24 cm * 30 cm). The number
      of EI was recorded and the AGD calculated. This AGD was compared with the mean
      AGD of 47 conventional full-field digital mammography (FFDM) systems. RESULTS: A
      total of 62,466 examinations were analyzed. EI had to be taken in 0.6 %
      (199/32,766) of all PCM examinations and 0.3 % (90/29 700) of all CR
      examinations. This corresponded to a total of 327 and 191 EI for the PCM and CR
      systems, respectively. More than one quarter of the examinations with EI were
      necessary because the breast was not properly positioned in the original image
      (PCM 31 %, CR 29 %). The mean AGD per EI was 0.7 +/- 0.1 mGy for the PCM and 2.6
      +/- 1.2 mGy for the CR system. The mean AGD for all breast thicknesses for FFDM
      was 1.4 +/- 0.3 mGy. CONCLUSION: In general, large breasts cannot be imaged with
      just one image per view. The number of examinations where EI are needed is
      doubled with the 24 cm * 26 cm detector of the PCM system. However, the absolute
      number is small. The total dose, as the sum of the original and the EI, is equal
      to the mean AGD of a single image of the FFDM systems and lower than the dose of
      a single image with the CR system.

PMID- 24563412
TI  - Radiological monitoring of the treatment of solid tumors in practice.
AB  - PURPOSE: Thanks to advances in cancer therapy, the diagnosis of "incurable
      cancer" is increasingly able to be changed to a chronic disease that is
      manageable over long periods, resulting in a change in the clinical management of
      cancer patients with solid tumors. New parameters are needed to measure the
      success of targeted therapy in clinical trials. MATERIALS AND METHODS: Review
      article on the basis of selective literature research. RESULTS: In order to
      assess how well solid tumors respond to treatment, size-based criteria called
      RECIST (Response Evaluation Criteria in Solid tumors) have been defined. These
      criteria have been validated in large oncology trials and are currently used most
      frequently. New molecular therapies often do not - or at least do not immediately
      - reduce the size of a tumor. Therefore, RECIST evaluation should be critically
      assessed especially in the case of modern therapies. Any additional available
      tumor biology information should be considered. In radiology new methods and
      developments of RECIST have been introduced to better assess the success of
      targeted therapy. CONCLUSION: Assessment according to RECIST has been proven for
      the follow-up of classic tumor therapy. For the monitoring of targeted therapies,
      new parameters are often required. Therefore, some specific tumor- and therapy
      adapted criteria have already been defined to better evaluate treatment success
      in clinical trials.

PMID- 24563413
TI  - 7,12-Dimethylbenz(a)anthracene-induced myelotoxicity differs in mice selected for
      high or low acute inflammatory response: relationship with aryl hydrocarbon
      receptor polymorphism.
AB  - Polycyclic aromatic hydrocarbons, such as 7,12-dimethylbenz(a)anthracene (DMBA),
      are environmental pollutants that exert multiple toxic and carcinogenic effects.
      Studies showed that these effects are mediated by activation of the aryl
      hydrocarbon receptor (AhR) and modulated by allelic variants of Ahr gene. Here,
      we investigated the effects of DMBA treatment in the inflammatory response and
      bone marrow (BM) hematopoietic function of maximal acute inflammatory response
      (AIRmax) and minimal acute inflammatory response (AIRmin) heterogeneous mouse
      lines selected for high and low acute inflammatory responsiveness, respectively.
      The phenotypic selection resulted in the segregation of the Ahr(d) and Ahr(b1)
      alleles that confer low and high receptor ligand-binding affinity, respectively,
      in AIRmax and AIRmin mice. We observed a reduction in BM mature granulocyte
      population in AIRmin mice 24 hours after DMBA treatment while both blast and
      immature myeloid cells were increased. Proliferation and differentiation of BM
      myeloid cells in response to in vitro granulocyte-macrophage colony-stimulating
      factor stimulus were impaired in AIRmin-treated mice. These DMBA effects on
      myeloid BM cells (BMCs) affected the in vivo leukocyte migration to an
      inflammatory site induced by polyacrylamide beads (Biogel P-100, Bio-Rad, France)
      injection in AIRmin mice. On the other hand, these alterations were not observed
      in DMBA-treated AIRmax mice. These data indicate that DMBA affects myeloid cell
      differentiation and inflammatory response and Ahr(b1) allele in the genetic
      background of AIRmin mice contributes to this effect. 

PMID- 24563414
TI  - Toxicity assessment of 7 anticancer compounds in zebrafish.
AB  - Toxicity is one of the major reasons for failure in drug development. Zebrafish,
      as an ideal vertebrate model, could also be used to evaluate drug toxicity. In
      this study, we aimed to show the predictability and highlight novel findings of
      toxicity in zebrafish model. Seven anticancer compounds, including triptolide
      (TP), gambogic acid (GA), mycophenolic acid (MPA), curcumin, auranofin,
      thalidomide, and taxol, were assessed in zebrafish for their toxicity. Three
      compounds (GA, TP, and taxol) showed highest acute lethality, with 50% lethal
      concentration ~ 1 MUmol/L. Missing tails, severe pericardial edema, and enlarged
      yolk sacs were observed in MPA-treated embryos. The development of pectoral fins
      was severely disturbed in thalidomide-, GA-, and TP-treated embryos. Bradycardia
      was observed in MPA- and thalidomide-treated groups. Our findings suggested that
      the zebrafish are a good model for toxicity assessment of anticancer compounds. 

PMID- 24563415
TI  - Mitochondrial oxidative stress-induced epigenetic modifications in pancreatic
      epithelial cells.
AB  - Emerging studies have linked prooxidative carbamate compound exposures with
      various human pathologies including pancreatic cancer. In these studies, our aim
      was to examine mitochondrial oxidative stress-mediated aberrant chromatin
      responses in human pancreatic ductal epithelial cells. Posttranslational histone
      modifications, promoter DNA methylation, and micro-RNA (miRNA) expression
      patterns were evaluated following induction of mitochondrial oxidative stress by
      N-succinimidyl N-methylcarbamate exposure. In treated cells, perturbation in
      mitochondrial machinery led to hypermethylation of p16 and smad4 gene promoters
      and downregulation of respective gene products. Posttranslational histone
      modifications that include hypoacetylation of acetylated histone (AcH) 3 and
      AcH4, hypermethylation of monomethylated histone 3 at lysine 9 and trimethylated
      histone 4 at lysine 20 ubiquitinated histone (uH) 2A/uH2B, and increased
      phosphorylation of H2AX and H3 were observed in the treated cells. Altered
      expression of miRNAs denoted possible location of corresponding genes at
      oxidatively damaged fragile sites. Collectively, our results provide a direct
      role of mitochondrial oxidative stress-mediated epigenetic imbalance to perturbed
      genomic integrity in oxygen radical-induced pancreatic injury. Further,
      identification and characterization of molecular switches that affect these
      epigenomic signatures and targets thereof will be imperative to understand the
      complex role of redox-regulatory network in pancreatic milieu. 

PMID- 24563416
TI  - Ear-catching? Real-world distractibility scores predict susceptibility to
      auditory attentional capture.
AB  - Although many of the everyday distractions that we encounter are auditory, most
      research on distractor processing to date has focused on the visual domain. A
      common measure of everyday distractibility is the Cognitive Failures
      Questionnaire (CFQ; Broadbent, Cooper, FitzGerald, & Parkes British Journal of
      Clinical Psychology 21: 1-16, 1982), which has previously been successfully
      linked with performance on controlled visual-attention tasks (e.g., Forster &
      Lavie Psychological Science 18: 377-381, 2007; Kanai, Dong, Bahrami, & Rees
      Journal of Neuroscience 31: 6620-6626, 2011; Tipper & Baylis Personality and
      Individual Differences 8: 667-675, 1987), such that high scorers tend to display
      greater distractor interference than do low scorers. We examined whether the same
      relationship would hold in hearing. Participants performed an auditory
      attentional-capture task, by responding to a target sound while ignoring an
      irrelevant singleton distractor (presented on half of the trials). We found that
      CFQ score successfully predicted distractor interference, since participants who
      reported being more distractible in everyday life produced more errors in the
      presence of the irrelevant singleton than did low scorers on the CFQ. This
      finding is the first to demonstrate a relationship between auditory distractor
      interference and everyday distractibility, and it confirms that performance on
      this type of laboratory-based attentional-capture task can successfully be
      related to behavior outside the laboratory.

PMID- 24563419
TI  - Intensive cardiovascular risk reduction induces sustainable changes in expression
      of genes and pathways important to vascular function.
AB  - BACKGROUND: Healthy lifestyle changes are thought to mediate cardiovascular
      disease risk through pathways affecting endothelial function and progression of
      atherosclerosis; however, the extent, persistence, and clinical significance of
      molecular change during lifestyle modification are not well known. We examined
      the effect of a rigorous cardiovascular disease risk reduction program on
      peripheral blood gene expression profiles in 63 participants and 63 matched
      controls to characterize molecular responses and identify regulatory pathways
      important to cardiovascular health. METHODS AND RESULTS: Dramatic changes in
      dietary fat intake (-61%; P<0.001 versus controls) and physical fitness (+34%;
      P<0.001) led to significant improvements in cardiovascular disease risk factors.
      Analysis of variance with false discovery rate correction for multiple testing
      (P<0.05) identified 26 genes after 12 weeks and 143 genes after 52 weeks that
      were differentially expressed from baseline in participants. Controls showed
      little change in cardiovascular disease risk factors or gene expression.
      Quantitative reverse transcription polymerase chain reaction validated
      differential expression for selected transcripts. Lifestyle modification
      effectively reduced expression of proinflammatory genes associated with
      neutrophil activation and molecular pathways important to vascular function,
      including cytokine production, carbohydrate metabolism, and steroid hormones.
      Prescription medications did not significantly affect changes in gene expression.
      CONCLUSIONS: Successful and sustained modulation of gene expression through
      lifestyle changes may have beneficial effects on the vascular system not apparent
      from traditional risk factors. Healthy lifestyles may restore homeostasis to the
      leukocyte transcriptome by downregulating lactoferrin and other genes important
      in the pathogenesis of atherosclerosis. Clinical Trial Registration- URL:
      www.clinicaltrials.gov. Unique identifier: NCT01805492.

PMID- 24563422
TI  - Genetic tests could detect high risk of aggressive prostate cancer.

PMID- 24563421
TI  - [Evaluation of the nationwide DEGUM breast ultrasound training program].
AB  - PURPOSE: The aim of this study was to evaluate the quality standard of the
      nationwide breast ultrasound training program of the German Society of Ultrasound
      in Medicine (DEGUM) through objective parameters. MATERIALS AND METHODS: 10
      quality criteria, based on the recommendations of The National Association of
      Statutory Health Insurance Physicians (KBV), were defined for this study. All
      training units of the DEGUM received a questionnaire. The questionnaires and
      training material were analyzed. RESULTS: All units met the required criteria
      pertaining to the trainer's qualification, duration per training course and the
      maximum number of participants per ultrasound machine. Only 1 course did not
      fulfill the required 50 % practical training time. The requirements to
      participate in the graduate course (200 self-made and documented cases) were not
      clearly conceived and a defined training log could be improved. CONCLUSION: DEGUM
      breast ultrasound training offers trainees a high level of education based on the
      requirements of the KBV. Despite the high quality of training, the content of
      course announcements could be improved and an official and structured educational
      index could be meaningful.

PMID- 24563420
TI  - Contrast-enhanced ultrasound (CEUS) for the evaluation of focal liver lesions - a
      prospective multicenter study of its usefulness in clinical practice.
AB  - PURPOSE: To assess the value of contrast-enhanced ultrasound (CEUS) for
      differentiating malignant from benign focal liver lesions (FLLs) and for
      diagnosing different FLL types. MATERIAL AND METHODS: CEUS performed in 14
      Romanian centers was prospectively collected between February 2011 and June 2012.
      The inclusion criteria were: age > 18 years; patients diagnosed with 1 - 3 de
      novo FLLs on B-mode ultrasound; reference method (computed tomography (CT),
      magnetic resonance imaging (MRI) or biopsy) available; patient's informed
      consent. FLL lesions were characterized during CEUS according to the European
      Federation of Societies for Ultrasound in Medicine and Biology guidelines. For
      statistical analysis, indeterminate FLLs at CEUS were rated as false
      classifications. RESULTS: A total number of 536 cases were included in the final
      analysis, 344 malignant lesions (64.2 %) and 192 benign lesions (35.8 %). The
      reference method was: CT/MRI - 379 cases (70.7 %), pathological exam - 150 cases
      (27.9 %) and aspiration of liver abscesses - 7 cases (1.4 %). CEUS was conclusive
      in 89.3 % and inconclusive in 10.7 % of cases. To differentiate between malignant
      and benign FLLs, CEUS had 85.7 % sensitivity, 85.9 % specificity, 91.6 % positive
      predictive value, 77.1 % negative predictive value and 85.8 % accuracy. The CEUS
      accuracy for differentiation between malignant and benign liver lesions was
      similar in tumors with diameter <= 2 cm and those with diameter > 2 cm.
      CONCLUSION: CEUS represents a useful method in clinical practice for
      differentiating between malignant and benign FLLs detected on standard
      ultrasonography, and the results of this study are in concordance with previous
      multicenter studies: DEGUM (Germany) and STIC (France).

PMID- 24563423
TI  - Melanoma of non-sun exposed skin in a man with previous prostate cancer:
      recognition of a recently confirmed association.
AB  - BACKGROUND: The association of an increased risk to develop melanoma in patients
      with prostate cancer has recently been confirmed. PURPOSE: The postulated
      etiologic relationship between prostate cancer and the subsequent occurrence of
      melanoma is discussed. METHODS: A man with previous prostate cancer who developed
      melanoma on the plantar surface of his left great toe is described and the
      possibility of high levels of endogenous androgens promoting not only prostate
      cancer, but also increased risk of melanoma are reviewed. RESULTS: Modification
      of the host immune response, alteration of chromosome telomere length, and/or
      imbalance of androgen level (presenting as severe teenage acne) are potential
      mechanisms whereby high levels of endogenous androgens may contribute to the
      association between prostate cancer and risk of melanoma. CONCLUSIONS: An
      increased surveillance for melanoma should be considered in prostate cancer
      patients. Complete skin examination in men who have had prostate cancer
      especially in those individuals diagnosed with prostate cancer prior to age 68
      years-should regularly be performed.

PMID- 24563424
TI  - Combined Analysis of Phenotypic and Target-Based Screening in Assay Networks.
AB  - Small-molecule screens are an integral part of drug discovery. Public domain data
      in PubChem alone represent more than 158 million measurements, 1.2 million
      molecules, and 4300 assays. We conducted a global analysis of these data,
      building a network of assays and connecting the assays if they shared
      nonpromiscuous active molecules. This network spans both phenotypic and target
      based screens, recapitulates known biology, and identifies new polypharmacology.
      Phenotypic screens are extremely important for drug discovery, contributing to
      the discovery of a large proportion of new drugs. Connections between phenotypic
      and biochemical, target-based screens can suggest strategies for repurposing both
      small-molecule and biologic drugs. For example, a screen for molecules that
      prevent cell death from a mutated version of superoxide-dismutase is linked with
      ALOX15. This connection suggests a therapeutic role for ALOX15 inhibitors in
      amyotrophic lateral sclerosis. An interactive version of the network is available
      online (http://swami.wustl.edu/flow/assay_network.html). 

PMID- 24563425
TI  - Reproductive fitness and genetic transmission of tetralogy of Fallot in the
      molecular age.
AB  - BACKGROUND: Individuals with tetralogy of Fallot (TOF) now routinely survive to
      reproductive age and beyond. Reproductive fitness of adults with TOF and
      recurrence risks to offspring are of increasing interest in the modern era,
      especially given recent molecular genetic discoveries. METHODS AND RESULTS: After
      excluding individuals with known genetic syndromes, 543 unrelated adults with TOF
      underwent a detailed family history assessment and molecular characterization for
      rare copy number variations using high-resolution genome-wide microarrays. Men
      and women with TOF had significantly fewer offspring compared with an age-matched
      comparison group without congenital heart disease (CHD; P=0.0004). No aspect of
      rare copy number variation burden was a predictor of decreased reproductive
      fitness. Corresponding with the advent of modern surgical repairs, reproductive
      fitness of women began to exceed that of men (P=0.0490). Recurrence risk for CHD
      in offspring was 4.8%, with no significant differences between men and women with
      TOF. The risk of severe CHD in offspring (2.3%) far exceeded population
      expectations (relative risk, 15.6; 95% confidence interval, 7.9-31.0). Most cases
      of vertical transmission of CHD were not explained by the transmission of a large
      rare copy number variation. Although conotruncal lesions (31.5%) were the most
      commonly reported CHD in relatives, the familial spectrum of disease included
      many anatomically discordant lesions. CONCLUSIONS: Men and women with TOF have
      reduced reproductive fitness. Their offspring are at significantly elevated risk
      for severe CHD. These results support the importance of genetic counseling for
      both men and women with complex CHD. Many inherited genetic variants remain to be
      discovered.

PMID- 24563426
TI  - Paneth cells are also target of the ribotoxic lectin nigrin b.
AB  - Ribosome-inactivating lectins (RILs) are A-B type toxins like ricin whose
      molecular target is the large rRNA of eukaryotic ribosome. Administration of
      lethal doses of the RIL nigrin b isolated from elderberry (Sambucus nigra L.)
      bark triggers specific intestinal derangement. The aim of the present research
      was to explore the early effects of a lethal dose of nigrin b (16 mg/kg body
      weight) on the small intestine using light and electron microscopy to ascertain
      intestinal epithelium changes. 6 h after nigrin administration, the small
      intestine crypts began to show signs of damage with cells appearing at different
      stages of apoptosis. 16 h after injection crypts appeared more impaired,
      including the derangement of Paneth cells. The novelty of our results is that the
      Paneth cells in the small intestine in addition to stem cells are the early
      cellular targets for nigrin b.

PMID- 24563427
TI  - Substance abuse and psychosis. The strange case of opioids.
AB  - BACKGROUND: Psychoses correlated with substance abuse prove to be more common in
      cases involving cannabinoids, stimulants, hallucinogens, alcohol and polyabuse.
      Among substance abusers, it has not been ascertained whether opioids have a
      psychotic effect. OBJECTIVES: The aim of this review is to investigate whether,
      among substances of abuse, a distinction can be drawn between pro-psychotic and
      anti-psychotic agents on the basis of the relationship between these substances
      and psychosis. METHODS: Studies were identified by searching through multiple
      literature databases, including PubMed, Scopus, Web of Knowledge. Hand searches
      through reference lists of relevant reviews were used to complement the computer
      searches. RESULTS: Looking at the relationships linking substances of abuse with
      psychosis, a distinction can, in fact, be drawn between pro-psychotic and anti
      psychotic substances. Even if there are no differences in the addictive processes
      involved, opiates are the only sedative drugs that possess an anti-psychotic
      effect. CONCLUSIONS: The whole topic of opiate agonism merits is due for
      reconsideration: it is not only the anticraving action of opiate agonism, but
      also its effectiveness on the psychopathological level that qualifies it as to be
      viewed as a powerful tool in treating mental illness.

PMID- 24563428
TI  - Association of Tourette syndrome and obsessive-compulsive disorder with allergic
      diseases in children and adolescents: a preliminary study.
AB  - OBJECTIVES: To investigate the rate of allergic diseases including asthma,
      allergic rhinitis and eczema in children and adolescents diagnosed with obsessive
      compulsive disorder (OCD) (n:26) and/or Tourette syndrome (TS) (n:32) [OCD plus
      TS, n:13] compared to control subjects (n:35) [total, n:80]. PATIENTS AND
      METHODS: The symptoms of any allergic disease were assessed using the ISAAC
      questionnaire form. Allergy diagnoses were made by a pediatric allergy
      specialist. Skin prick tests were applied, and IgE levels and eosinophil counts
      were measured. RESULTS: While only one-fifth of the control subjects had allergic
      diseases, more than half of the children with TS and/or OCD had comorbid allergic
      diseases. Positive skin prick tests were greater in OCD patients compared to
      control subjects. There were no significant differences between the groups in
      terms of eosinophil counts or IgE levels. Among the allergic diseases, while
      allergic rhinitis was diagnosed at significantly higher rates in TS patients,
      eczema was significantly higher in OCD patients compared to control subjects.
      CONCLUSIONS: This preliminary study shows an association between allergic
      diseases and TS and/or OCD. The results revealing differences in associations
      between types of allergic disease (rhinitis or eczema) and neuropsychiatric
      disorder (tic disorder or OCD) need to be investigated in further studies with
      higher numbers of participants, and immune markers should be examined.

PMID- 24563429
TI  - Therapeutic effect of magnesium isoglycyrrhizinate in rats on lung injury induced
      by paraquat poisoning.
AB  - OBJECTIVE: The aim of this study was to investigate the effect of Magnesium
      Isoglycyrrhizinate (MgIG) on intercellular adhesion moledule-1 (ICAM-1) and
      matrix metalloproteinase-9 (MMP-9) in rats with Paraquat (PQ) poisoning and its
      potential mechanism. MATERIALS AND METHODS: 30 male Sprague Dawley rats were
      randomly divided into five groups, including normal control group, poisoned
      control group, low-dose MgIG group, medium-dose MgIG group and high-dose MgIG
      group. Each group was treated with corresponding dose of MgIG once on daily basis
      by intraperitoneal injection 24 hours later, and the normal control group and
      poisoned control group were injected with physiological saline. All the animals
      were killed 14 days after poisoning, the contents of ICAM-1 and matrix MMP-9 were
      determined. HE staining and Masson staining were performed, the hydroxyproline
      (HYP) content in the lung tissue was also determined, and the expressions of ICAM
      1 and MMP-9 were detected by immunohistochemical test. RESULTS: The contents of
      ICAM-1 and MMP-9 in the rat serum for all treatment groups were significantly
      decreased compared with those of the poisoned control group (p < 0.05, or <
      0.01), and the expressions of the two proteins were significantly down-regulated,
      especially for the medium dose group. CONCLUSIONS: There is an improvement effect
      of ICAM-1 and MMP-9 in rats with Paraquat poisoning for the medium dose of MgIG,
      capable of slowing down the process of pulmonary fibrosis to certain extent.

PMID- 24563430
TI  - The role of cefditoren in the treatment of lower community-acquired respiratory
      tract infections (LRTIs): from bacterial eradication to reduced lung inflammation
      and epithelial damage.
AB  - OBJECTIVES: Lower respiratory tract infections (LRTIs), including pneumonia and
      acute exacerbations of Chronic Obstructive Pulmonary Disease (COPD), are among
      the most common diagnoses in both outpatient and inpatient settings. Due to the
      burden of LRTIs healthcare providers must adopt practices focused on improving
      outcomes with the aim to reduce treatment failure and antibiotic resistances.
      Moreover, the role of acute and chronic infection in the pathogenesis of COPD has
      received considerable attention, since chronic infection can contribute to
      airways inflammation and COPD progression. This review discusses the role of
      cefditoren for the treatment of LRTIs, compared with the definition of
      "appropriate" of the WHO as "the cost-effective use of antimicrobials which
      maximizes clinical therapeutic effect while minimizing both drug-related toxicity
      and the development of antimicrobial resistance". RESULTS AND CONCLUSIONS:
      Cefditoren appears to meet the definition of "appropriate" for the treatment of
      LRTIs. In fact, this molecule shows an adequate pharmacokinetic profile without
      the need for any adjustment also in aged patients with mild renal impairment or
      mild-to-moderate hepatic dysfunction. The low drug-drug interaction potential of
      cefditoren can be an advantage also in poly-treated patients. The antimicrobial
      spectrum of cefditoren includes both Gram+ and Gram- bacteria, with high activity
      against Streptococcus pneumoniae, including drug-resistant strains, Haemophilus
      infuenzae and Moraxella chatarrhalis. Last, recent findings suggested that
      cefditoren can be a valid alternative to levofloxacin in outpatients with acute
      exacerbation of COPD; in this setting a treatment with cefditoren showed to be
      associated with a significant reduction of some key inflammatory markers involved
      in epithelial damage, including KL-6 and IL-6.

PMID- 24563418
TI  - Novel genetic approach to investigate the role of plasma secretory phospholipase
      A2 (sPLA2)-V isoenzyme in coronary heart disease: modified Mendelian
      randomization analysis using PLA2G5 expression levels.
AB  - BACKGROUND: Secretory phospholipase A2 (sPLA2) enzymes are considered to play a
      role in atherosclerosis. sPLA2 activity encompasses several sPLA2 isoenzymes,
      including sPLA2-V. Although observational studies show a strong association
      between elevated sPLA2 activity and CHD, no assay to measure sPLA2-V levels
      exists, and the only evidence linking the sPLA2-V isoform to atherosclerosis
      progression comes from animal studies. In the absence of an assay that directly
      quantifies sPLA2-V levels, we used PLA2G5 mRNA levels in a novel, modified
      Mendelian randomization approach to investigate the hypothesized causal role of
      sPLA2-V in coronary heart disease (CHD) pathogenesis. METHODS AND RESULTS: Using
      data from the Advanced Study of Aortic Pathology, we identified the single
      nucleotide polymorphism in PLA2G5 showing the strongest association with PLA2G5
      mRNA expression levels as a proxy for sPLA2-V levels. We tested the association
      of this SNP with sPLA2 activity and CHD events in 4 prospective and 14 case
      control studies with 27 230 events and 70 500 controls. rs525380C>A showed the
      strongest association with PLA2G5 mRNA expression (P=5.1*10(-6)). There was no
      association of rs525380C>A with plasma sPLA2 activity (difference in geometric
      mean of sPLA2 activity per rs525380 A-allele 0.4% (95% confidence intervals [
      0.9%, 1.6%]; P=0.56). In meta-analyses, the odds ratio for CHD per A-allele was
      1.02 (95% confidence intervals [0.99, 1.04]; P=0.20). CONCLUSIONS: This novel
      approach for single-nucleotide polymorphism selection for this modified Mendelian
      randomization analysis showed no association between rs525380 (the lead single
      nucleotide polymorphism for PLA2G5 expression, a surrogate for sPLA2-V levels)
      and CHD events. The evidence does not support a causal role for sPLA2-V in CHD.

PMID- 24563431
TI  - Antiviral activity of Holothuria sp. a sea cucumber against herpes simplex virus
      type 1 (HSV-1).
AB  - BACKGROUND: Finding the new bioactive compounds with antiviral activity from the
      natural resources are in interest of many drug discovery scientists. Sea cucumber
      is among the marine organisms a traditional food item in Asia with different
      applications in traditional medicine. METHODS: In current study, a cold water
      extract of the Holothuria sp, one type Persian Gulf's sea cucumber was evaluated
      for its antiviral effects against KOS strain of Herpes Simplex Virus tyoe 1 (HSV
      1) in cell culture. The half maximal inhibitory concentration (IC50) values were
      calculated for anti-adsorption activity and intracellular antiviral activity of
      the crude extract separately. RESULTS: The extract exhibited antiviral activity
      not only against the virus adsorption to the cells, but also on virus
      intracellular replication. The CC50 for sea cucumber extract was 32.57 mg/ml. The
      IC50 values for the inhibition of the virus adsorption to the cells and virus
      intracellular replication were 120.2 and 189.9 ug/ml respectively. Selectivity
      index (SI) value for anti-adsorption activity was 189 while that value for the
      extract's intracellular antiviral activity was 172. CONCLUSIONS: The results
      showed that Holothuria sp, water extract has remarkable antiviral effect against
      HSV-1 in cell culture and it is crucial to investigate the mechanism(s) of action
      of extract. Moreover, identification of the effective compound(s) within the
      extract would be necessary for future studies towards developing the new natural
      antiviral agent against HSV-1.

PMID- 24563432
TI  - Effect of SB203580 on pathologic change of pancreatic tissue and expression of
      TNF-alpha and IL-1beta in rats with severe acute pancreatitis.
AB  - OBJECTIVE: This study aimed to investigate the effect of SB203580 which is the
      inhibitor of p38 mitogen-activated protein kinase on pathologic change of
      pancreatic tissue and expression of tumor necrosis factor-alpha (TNF-alpha) and
      interleukin-1-beta (IL-1b) in rats with severe acute pancreatitis (SAP),
      Hematoxylin-eosin (HE) staining and immunohistochemistry were carried out in the
      present study. METHODS: Forty-five male Wistar rats were divided into three
      groups: the SAP group (N=15), SB203580-treated group (SB group) (N=15), and the
      control group (N=15). Severe acute pancreatitis was induced by injection of
      sodium taurocholate into the pancreatic duct. For SB203580-treated group,
      SB203580 were administered via intraperitoneal injection (10 mg/kg). Serum
      amylase activity was measured 6, 12 and 24 hours respectively after the
      operation. The pancreas tissue were stained with HE for histopathological
      evaluation and the expression of TNF-alpha and IL-1b in the pancreatic tissue
      were determined through inferior vena cava. RESULTS: The results show that the
      level of amylase in SAP group was higher than that in the other groups. Further,
      the pancreas tissues of SB group rats were observed more mildly edematous,
      hemorrhagic and with monocytes infiltration. Based on immunohistochemical
      staining, the expression of TNF-alpha and IL-1beta in SAP rats were significantly
      increased than those of the control group. However, those of SB203580-treated
      group were more significantly reduced than those of SAP group (p < 0.05).
      CONCLUSIONS: Those data suggest that SB203580, down regulating the expression of
      pro-inflammatory mediators such as TNF-alpha and IL-1beta, then through p38 MAPK
      signaling pathway inhibition, plays an important role in the treatment of SAP.

PMID- 24563433
TI  - Effects of rifaximin on indomethacin-induced intestinal damage in guinea-pigs.
AB  - AIM: Enterobacterial translocation into the gut mucosa is the first step required
      for activation of neutrophils and inducible nitric oxide synthase (iNOS),
      involved in the pathogenesis of indomethacin-induced intestinal lesions.
      Rifaximin may limit NSAID-associated intestinal damage by decreasing the
      bacterial load. We aimed to study the effect of rifaximin on indomethacin-induced
      intestinal damage in guinea-pigs. MATERIALS AND METHODS: Twenty-four guinea pigs,
      equally divided in four interventional groups (A-D), received indomethacin, given
      orally once daily (30 mg/kg) for three consecutive days. In groups B, C, D
      different doses of rifaximin (50 mg/kg, 100 mg/kg and 200 mg/kg) were given
      orally two hours before indometachin administration. Semi-quantitative grades
      were measure for gross findings, degenerative lesions, neutrophils and
      eosinophils infiltrates and iNOS immunopositivity. Statistical comparisons used
      Mann Whitney Test, with a Bonferroni correction for alpha (p <= 0.016). RESULTS:
      Statistical analysis of graded gross findings, microscopic degenerative lesions,
      endothelium damage and iNOS immunopositivity found no difference between A and B
      groups. Significant fewer gross findings (U = 3, p = 0.015), microscopic
      degenerative lesions (U = 2, p = 0.008) and lower grades for iNOS
      immunopositivity (U = 0, p = 0.002) were found in group C compared with group A.
      In group D, significant lower grades for iNOS immunopositivity were obtained (U =
      0, p = 0.002) compared with group A and fewer degenerative lesions without
      reaching statistical significance (U = 4, p = 0.026). CONCLUSIONS: 100 mg/kg of
      rifaximin proved efficient in preventing gut degenerative lesions induced by
      indomethacin in a guinea pig model, the iNOS activity being significantly
      decreased.

PMID- 24563434
TI  - Subclinical hypercortisol-assessment of bone fragility: experience of single
      osteoporosis center in Sicily.
AB  - AIM: Hypercortisolism is known to cause osteoporosis. Some evidence suggests that
      osteoporotic fractures may be the presenting manifestations of otherwise
      asymptomatic hypercortisolism. The aim of our research was to investigate the
      prevalence of subclinical hypercortisolism (SH) in postmenopausal women evaluated
      for bone fragility. PATIENTS AND METHODS: One hundred consecutive postmenopausal
      women attending the Osteoporosis Centre in the Department of Internal Medicine of
      the University of Messina (Messina, Italy), for the first time, were screened and
      a total of 50 patients (age 58+/-5 years) were studied. Hypercortisolism was
      diagnosed by unsuppressed serum cortisol levels after 2 day low dose
      dexamethasone suppression test. RESULTS: Among the 50 postmenopausal women
      studied, 3 had SH. This prevalence was 6%. The three patients with SH had a
      normal bone mineral density (BMD) at lumbar spine and were osteopenic at femoral
      neck, and presented one or more vertebral fractures at spinal radiography.
      CONCLUSIONS: Physicians should always consider SH among the causes of bone
      fragility, especially in individuals with vertebral fractures and the presence of
      an only slightly reduced BMD.

PMID- 24563435
TI  - Oxidative stress in rats with hyperhomo-cysteinemia and intervention effect of
      lutein.
AB  - AIM: The current study aims to explore the possible molecular mechanism of
      hyperhomocysteinemia (HHcy) mediated atherosclerosis (AS) and to find an
      effective intervention method for AS. MATERIALS AND METHODS: A total of 40 Wistar
      rats were equalized into four groups: blank control, HHcy, folacin intervention,
      and lutein intervention groups. HHcy rat models were established. The
      intervention groups were respectively lavaged with folacin and lutein. Oxidative
      stress states, the levels of nitric oxide (NO) and endothelin-1 (ET-1), as well
      as the expression of nuclear factor (NF)-kappaB p65 and intercellular adhesion
      molecule (ICAM)-1 were compared. RESULTS: In the HHcy rats, the activity of serum
      superoxide dismutase (SOD) and glutathione peroxidase (GPx) significantly
      decreased, whereas the malondialdehyde content and hydroxyl radical level
      noticeably increased, indicating that the rats stayed in aggravated oxidative
      stress states. Lutein intervention inhibited HHcy-induced oxidative stress
      excitement. In the HHcy rats, the NO level significantly decreased, whereas the
      ET-1 level significantly increased, indicating that HHcy mediated vascular
      endothelial dysfunction. Lutein reversed such dysfunction. In the HHcy rats, the
      mRNA and protein expression of SOD2 and GPX1 in the aortic wall tissue decreased,
      whereas that of NF-kappaB p65 and ICAM-1 increased. Lutein significantly
      upregulated the mRNA and protein expression of SOD2 and GPx1 and downregulated
      the expression of NF-kappaB p65 and ICAM-1. CONCLUSIONS: Oxidative stress and
      inflammation are the important mechanisms of HHcy-mediated AS. In particular,
      HHcy-induced aggravated oxidative stress may function as the initial AS-mediating
      mechanism, upregulating the expression of NF-kappaB p65 and ICAM-1 and thereby
      becoming associated with AS. Lutein noticeably intervenes in and inhibits Hcy
      mediated oxidative stress excitement and downregulates the expression of
      inflammation-associated informational molecules.

PMID- 24563436
TI  - Cardiovascular risk in patients without known cardiovascular disease.
AB  - Understanding the risks of atherosclerotic cardiovascular disease (CVD) allows
      for better patient education and management. Multiple risk models have been
      validated in large patient populations and provide insights into the risks
      associated with CVD. When assessing such risks, we suggest using a model that
      predicts myocardial infarction, cardiovascular death, and/or cerebrovascular
      events. In this review, we analyze several risk models and stratify the risks
      associated with CVD. We suggest that appropriate profiling of patients at-risk of
      CVD will lead to better physician recognition and treatment of modifiable risk
      factors, appropriate application of ATP III treatment for hyperlipidemia, and
      achieving optimal blood pressure control. 

PMID- 24563437
TI  - Correlation between coronary microvascular function and angina status in patients
      with stable microvascular angina.
AB  - BACKGROUND: Classical anti-ischemic drugs are the first-line form of treatment in
      patients with microvascular angina (MVA), but they often fail to achieve a
      satisfactory control of angina symptoms. It is unknown whether there is any
      relation between improvement of angina status and changes in microvascular
      function induced by classical anti-ischemic drugs in MVA patients. AIM: To assess
      whether, in MVA patients, the effects of classical anti-ischemic drugs on
      symptoms and quality of life (QoL) are related to changes in coronary
      microvascular function. PATIENTS AND METHODS: We studied 51 patients (59+/-10
      years; 15 men) with MVA. Coronary blood flow (CBF) response to adenosine (ADO)
      and to cold pressor test (CPT), Seattle Angina Questionnaire (SAQ) and EuroQoL
      scale were assessed at baseline, in pharmacological washout, and after 12 months
      under anti-ischemic therapy. Patients were divided into 2 groups: (1) Group 1
      included patients with no improvement of QoL (EuroQoL score change < 10 points);
      (2) Group 2 included patients with QoL improvement (increase in EuroQoL score >=
      10 points). RESULTS: At baseline, the 2 groups were similar in age, gender,
      cardiovascular risk factors, CBF response to ADO and to CPT, SAQ and EuroQoL
      scores. At follow-up the 2 groups differed only for beta blockers use (27% vs.
      88% in group 1 and 2, respectively; p < 0.001). A significant improvement in SAQ
      score was observed only in group 2. CBF response to both ADO and CPT showed a
      similar improvement in the 2 groups. No relation was found between changes in
      coronary microvascular function and in angina status. CONCLUSIONS: In MVA
      patients beta-blockers are more effective than other anti-ischemic drugs in
      improving angina symptoms. The improvement of angina status does not seem to be
      mediated by changes in coronary microvascular function.

PMID- 24563438
TI  - The role of hemodynamic and vasoactive substances on hepatopulmonary syndrome.
AB  - BACKGROUND: Hepatopulmonary syndrome (HPS) is a chronic hepatic complication
      characterized by defect in arterial oxygenation induced by pulmonary vascular
      dilatation and vasoactive substances in the setting of chronic liver disease
      (CLD). This study is to investigate the abnormality of hemodynamic and vasoactive
      substances in hepatopulmonary syndrome. PATIENTS AND METHODS: From September 2007
      to September 2012, 58 patients with HPS in the General Surgery Department and
      Transplantation Center of Renji Hospital were enrolled for the case-control
      study. HPS patients enrolled were referred to as group H, CLD without HPS to as
      group C and case controls to as group N. Hemodynamic parameters of the systemic
      and pulmonary circulations as well as vasoactive substances in the radial and
      pulmonary arteries were measured in all patients. Univariate and multiple
      regression analysis were performed afterwards. RESULTS: The mean pulmonary
      arterial pressure, pulmonary artery wedge pressure, systemic vascular resistance
      and pulmonary vascular resistance (PVR) in HPS patients were significantly lower
      than those in CLD patients without HPS (p < 0.05). The nitrite-to-nitrate ratio
      (NO2-/NO3-), endothelin-1 (ET-1) and tumor necrosis factor-alpha (TNF-alpha) in
      the radial and pulmonary arteries differed significantly among group H, group C
      and case controls (group N) separately (p < 0.05). The vasoactive intestinal
      peptide and 6-keto-prostaglandin-F1alpha in the radial and pulmonary arteries of
      group H were significantly higher than those in group N (p < 0.05). The NO2(
      )/NO3(-) levels correlated negatively with PVR (r = -0.535, p < 0.05) and
      Endothelin-1 (r = -0.624, p < 0.05). CO (p < 0.05), CI (p < 0.05), SI (p < 0.05)
      and TNF-alpha (p < 0.05) level are considered significantly when performed with
      multiple regression analysis. CONCLUSIONS: The CO increases and PVR decreases in
      HPS patients. The abnormally elevated NO2-/NO3- level in the pulmonary
      circulation leads to pulmonary vasodilation. ET-1 may induce nitric oxide
      synthesis and correlated negatively with PVR in HPS. CO, CI, SI and TNF-alpha
      level are independent risk factors for HPS patients' survival.

PMID- 24563439
TI  - Higher red cell distribution width values are associated with impaired exercise
      capacity during exercise treadmill testing in patients without obstructive
      coronary disease: a preliminary study.
AB  - BACKGROUND: Red cell distribution width (RDW) is associated with poor
      cardiovascular outcomes. We aimed to find out if this association could be
      explained by impaired exercise capacity in patients without obstructive coronary
      artery disease (CAD). PATIENTS AND METHODS: The patients who underwent exercise
      treadmill test (ETT) who have non-obstructive CAD and were free of heart failure
      symptoms were evaluated. Total of 132 patients were enrolled, and patients were
      divided into three groups according to their Metabolic Equivalent Task (MET)
      level measured by exercise treadmill test (ETT): Less than 7 METs (group 1), 7-10
      METs (group 2) and greater than 10 METs (group 3). RESULTS: The patients in Group
      1 had significantly higher RDW levels (16.46 +/- 2.79) compared to Group 2 (15.05
      +/- 2.03) and Group 3 (14.52 +/- 1.37), independent of hemoglobin and hematocrit
      values. Significant differences for age, gender, duration of ETT and Duke
      Treadmill Score were also found in proportion to the reduced exercise capacity.
      In multivariate analysis, only duration of ETT (beta = 1.017, p = < 0.001) and
      RDW (beta = 0.040, p = 0.026) were found as independent variables, which had
      statistically significant effects on METs. CONCLUSIONS: We found an independent
      association between RDW and exercise capacity in patients free of obstructive
      coronary disease suggesting that patients with elevated RDW values are expected
      to have impaired exercise capacity.

PMID- 24563440
TI  - The relationship between blood lactate, carboxy-hemoglobin and clinical status in
      CO poisoning.
AB  - AIM: We aimed to determine the relationship between blood lactate, carboxy
      hemoglobin (COHb) levels and the severity of clinical findings in patients with
      CO poisoning. PATIENTS AND METHODS: Patients over 18 years old and of both gender
      who were admitted to Emergency Department with the diagnosis of CO poisoning
      between 10.02.2008 and 17.03.2011 were enrolled in this study. Detailed physical
      examination of each patient was performed, patients and their relatives were
      informed about the study and written consents were noted. The levels of
      consciousness, physical examination findings, electrocardiographic findings,
      Glasgow Coma Scale (GCS) scores, laboratory results (lactate, COHb, CK-MB,
      Troponin-I levels) and applied treatments [normobaric oxygen therapy (NBOT),
      hyperbaric oxygen therapy (HBOT)] were recorded to standart data entry form for
      each patient. "SPSS for Windows version 18" package program was used for
      statistical analysis of the data. RESULTS: Total 201 patients were included in
      this study. Thirty five patients (17.4%) received HBOT and lactate; COHb, CKMB,
      Troponin-I levels of this group were higher than the other patients. Lactate and
      COHb levels were statistically significantly higher in patients with GCS < 15
      than the ones with GCS = 15 (p < 0.01). The patients whose both Troponin-I and CK
      MB levels increased have higher lactate levels (p = 0.038), but COHb levels of
      these patients did not change (p = 0.495). CONCLUSIONS: According to our study,
      blood lactate and COHb levels were both correlated with the changes of
      consciousness in CO poisoning. Blood lactate levels together with COHb in
      defining indications for HBO treatment might be suggested.

PMID- 24563442
TI  - MRI appearances of stage IE/IIE extranodal NK/T-cell lymphoma, nasal type, in the
      upper aerodigestive tract.
AB  - BACKGROUND: The clinical symptoms of NK/T-cell lymphoma at presentation are
      nonspecific and may mimic those of other benign nasal diseases such as rhinitis
      and nasal polypus. However, radiologic studies regarding this aggressive clinical
      course entity are limited. AIM: To review 123 newly diagnosed MRI appearances in
      patients with extra-nodal NK/T-cell lymphoma, nasal type, in a large cohort and
      determine the characteristic imaging findings. SUBJECTS AND METHODS: We
      investigated the magnetic resonance imaging (MRI) findings of patients with newly
      diagnosed stage IE/IIE extranodal NK/T-cell lymphoma, nasal type, in the upper
      aerodigestive tract. RESULTS: Most nasal cavity patients (63.4%) showed extra
      nasal cavity involvements. The polypoid pattern was most frequently seen (55.3%),
      followed by the infiltrative (27.6%) and combined (17.1%) patterns. The polypoid
      pattern tended to develop in the nasal cavity group, while the infiltration
      pattern was more common in the non-nasal cavity group (63.4% vs. 60.0%, p <
      0.001). Homogeneous iso-intensity was seen in 97.6%, 88.6% and 56.1% of cases on
      T1-, T2-weighted images and post-contrast images, respectively. Bone destruction
      and necrosis were observed in 44.7% and 56.3% of patients. Both tumour necrosis
      and bone destruction were related to tumour size (p = 0.008, 0.001). Only 12.2%
      of patients had cervical lymphadenopathy Multi-region involvement, irregular
      growth pattern, predisposition to necrosis and bone destruction, and little
      lymphadenopathy are valuable for diagnosis and can be used to differentiate these
      tumours from other malignant tumours. CONCLUSIONS: Our large cohort study of MRI
      of NK/T cell lymphoma, nasal type, revealed the features of this lymphoma on MRI
      including some radiologic signs never reported earlier; these findings are
      invaluable for early diagnosis and may aid future studies aiming to predict the
      prognosis and response to therapy.

PMID- 24563441
TI  - Prognostic and predictive significance of plasma hepatocyte growth factor and
      carcinoembryonic antigen in non-small lung cancer after surgery.
AB  - OBJECTIVES: Scatter factor, also known as hepatocyte growth factor (SF/HGF), is a
      polypeptide growth factor with a number of biologic activities, including cell
      scattering, stimulation of cell motility, mitogenesis, morphogenesis,
      angiogenesis, and cellular invasiveness, it is thought to be important in the
      growth and spread of several carcinomas. We assessed whether preoperative plasma
      levels of HGF and carcinoembryonic antigen (CEA) can enhance the accuracy of
      standard models for predicting pathologic features and clinical outcomes.
      PATIENTS AND METHODS: The study comprised 45 consecutive patients treated with
      surgery for clinically localized non-small-cell lung cancer. HGF and CEA were
      measured using the commercially available immunoassay. Multivariate logistic
      regression was used to assess the relationship between plasma HGF/CEA and
      pathologic features. Multivariate Cox regression was used to predict disease
      recurrence. RESULTS: Patients with lung squamous cell cancer (SCC) more
      frequently had higher plasma HGF, whereas CEA levels were significantly elevated
      in patients with non-SCC histology. Preoperative plasma HGF and CEA levels were
      not the independent predictors of overall survival. CONCLUSIONS: Preoperative
      plasma levels of HGF and CEA are not the independent predictors of non-small lung
      cancer disease recurrence and metastasis after surgery; HGF is a predictor of
      lung squamous cell cancer. Use of HGF may help in therapeutic decision-making and
      estimate the histological type of NSCLC.

PMID- 24563444
TI  - Histological and ultra-structural effects of rapid muscle expansion through
      intramuscular administration of carbon dioxide: an intra-operative study in an
      animal model.
AB  - INTRODUCTION: Carbon dioxide (CO2) therapy refers to trans-cutaneous or sub
      cutaneous administration of CO2 for therapeutic purposes, and recent studies have
      pointed out that it produces a vasodilation effect after it is locally injected,
      which helps amplify the reconstructive potentiality of an expanded-muscle flap.
      MATERIALS AND METHODS: Thirty male Wistar rats, weighting between 350 and 400 g,
      were randomly divided into three groups of 10. In the first group, single intra
      operative rapid expansion was carried out under the right latissimus dorsi
      muscle. In the second group, for five days prior to surgery, a pre-treatment with
      intramuscular injections of CO2 was performed. The third group served as
      controls. For each group, the latissimus dorsi muscle was fixed as soon possible
      after mice died, and ultrathin sections of it examined with transmission electron
      microscope. RESULTS: In the treated group, the majority of expanded muscles
      showed a normal striation pattern, whereas a few fibers showed mild
      disorganization of the myo-filaments in the sarcomeres, which appeared
      overstretched (average 2.37 um). CONCLUSIONS: This evidence could demonstrate a
      greater capacity of muscle recovery after treatment by CO2 expansion.

PMID- 24563443
TI  - Multiple lipomatosis after stem cell trasplant and chemotherapy: a case report.
AB  - BACKGROUND: Lipomas are the most common type of soft tissue benign tumor. They
      can be either isolated entities or involved in a multiple lipomatosis, which may
      have a familial basis or be an acquired condition. AIM: Chemotherapy and/or blood
      stem cell transplantation may be plausible causes of multiple lipomatosis.
      MATERIALS AND METHODS: A 28 year-old patient was diagnosed with non-seminomatous
      germ cell left testicular cancer. The patient was addressed to chemotherapy and
      peripheral blood stem cell chemomobilization. After stem cells collection, the
      patient underwent autologous peripheral blood stem cell transplant. RESULTS: A
      subsequent de novo multiple lipomatosis onset developed. CONCLUSIONS: Although
      this is a preliminary study and further elaborations are needed, dermatologists
      and surgeons facing with multiple lipomatosis should consider previous
      chemotherapy and peripheral blood stem cell mobilization/transplant as possible
      causes of its onset.

PMID- 24563445
TI  - A case of adult-onset Still's disease presenting with multifocal central serous
      chorioretinopathy.
AB  - Adult-onset Still's disease (AOSD) is a rare systemic inflammatory disorder of
      unknown etiology with no specific histological features. In this study, we
      reported a 43-year-old woman who developed AOSD with multifocal central serous
      chorioretinopathy (CSC). Up to now, the patient is still on close follow-up.
      Besides, we reviewed the literature emphasized on the ophthalmological features
      of AOSD. 

PMID- 24563446
TI  - Regional difference of genetic factors for congenitals cataract. The results of
      congenital cataract screening under normal pupil conditions for infants in
      Tianjin city.
AB  - PURPOSE: To inquire into the morbidity of congenital cataract which affects the
      visual development of infants in Tianjin, find the proportion of cases caused by
      genetic factors, and to provide the baseline information for discovering
      amblyopia in an early stage so as to reduce vision disability. MATERIALS AND
      METHODS: Babies no more than two months old were screened for congenital cataract
      under normal pupil conditions. The check-up was performed using ophthalmoscope
      and a portable slit lamp. RESULTS: Among the 268,989 babies (537,978 eyes) being
      checked, 44 cases (75 eyes) of congenital cataract (13 unilateral cases and 31
      bilateral cases) were detected and a morbidity rate of 0.0160/00 was reported. 13
      of the 44 babies (0.0480/00) face difficulties in vision development. In the 44
      positive cases, 7 had a family history of congenital cataract (15.91%), 8
      (18.18%) had high risk factors and the other 29 cases (65.91%) reported no known
      reasons. CONCLUSIONS: Babies eyes screening under normal pupil conditions is an
      effective, rapid and acceptable method for discovering congenital cataract cases.
      Unlike findings in other related literatures, we found that genetic factors
      accounted for 15.91% of the incidence of congenital cataract, while 65.91% cases
      can't be explained.

PMID- 24563448
TI  - Radiographic evaluation of the prevalence of enamel pearls in a sample adult
      dental population.
AB  - AIM: Enamel pearls are a tooth anomaly that can act as contributing factors in
      the development of periodontal disease. Studies that have addressed the
      prevalence of enamel pearls in populations were scarce. The purpose of this study
      was to evaluate the prevalence of enamel pearls in the permanent dentition of
      Turkish dental patients by means of panoramic radiographs. PATIENTS AND METHODS:
      Panoramic radiographs of 6912 patients were examined for the presence of enamel
      pearls. All data (age, sex and systemic disease or syndrome) were obtained from
      the patient files and analyzed for enamel pearls. Descriptive characteristics of
      sexes, jaws, and dental localization were recorded. The Pearson chi-squared test
      was used. RESULTS: Enamel pearls were detected in 5.1% of subjects and 0.85% of
      the teeth examined. Prevalence of enamel pearls was higher in males (6.58%)
      compared to females (3.96%). The mandibular first was the most commonly affected
      tooth. Enamel pearls were significantly more common in the mandibula compared
      with the maxilla (81.2% cf 18.8% respectively, p = 0.000). No statistically
      significant differences were found between the right-side and left-side
      occurrences. CONCLUSIONS: With the prevalence of 5.1% among the Turkish
      population, every possible effort should be made for locating of this anomaly
      especially in molars because it might be useful for prevention periodontal
      problems.

PMID- 24563447
TI  - Genes relevant with osteoarthritis by comparison gene expression profiles of
      synovial membrane of osteoarthritis patients at different stages.
AB  - BACKGROUND: This study aimed to identify biological markers about osteoarthritis
      (OA) which is a polygenic disease by investigating the gene expression profiles
      of the synovium samples from early-stage and end-stage OA patients for the
      diagnosis and treatment of OA. METHODS: The gene expression profile of GSE32317
      was downloaded from Gene Expression Omnibus (GEO) database, including 10 samples
      from early-stage OA patients and 9 samples from end-stage OA patients. The
      differentially expressed genes (DEGs) were identified by Significance Analysis of
      Microarrays. The co-expression network of DEGs was constructed by Pearson
      correlation test. Then, modules in the constructed co-expression network were
      selected by MCODE Plugin. What's more, EASE (Expression Analysis Systematic
      Explorer) was used to define the significant functions and pathways in the
      identified modules. RESULTS: Total 419 DEGs were identified, among which 112 were
      up-regulated and 307 down-regulated. We selected 7 statistically significant
      modules with gene number above 10 and phenotypic correlation test of modules
      showed that all the modules had significant correlation with OA (p < 0.05). The
      genes of module 1, module 2 and module 7 were significantly related to immune
      system functions, protein glycosylation functions, bone, chondrocytes and
      cartilage functions, respectively. The most significant pathway in module 3 and
      module 5 was Wnt signal pathway, and in module 4 was Toll-like receptor signal
      pathway. CONCLUSIONS: DEGs related to immune response, cartilage development,
      protein glycosylation, muscle development, and DEGs participated in the Wnt
      signaling pathway and Toll-like receptor (TLR) signaling pathway might be the
      potential target genes for the OA treatment.

PMID- 24563449
TI  - Long-term functional and clinical follow-up of patients with heart failure with
      recovered left ventricular ejection fraction after beta-blocker therapy.
AB  - BACKGROUND: Some patients with left ventricular systolic dysfunction (LVSD) have
      a dramatic improvement in left ventricular ejection fraction (LVEF) after beta
      blockade. No study has analyzed the long-term echocardiographic and clinical
      follow-up of this subgroup of patients. METHODS AND RESULTS: We included in this
      analysis 174 consecutive patients with LVSD who had an LVEF>=45% after beta
      blockade. We performed a long-term echocardiographic follow-up (median 7.7 [4
      9.9] years) and clinical follow-up (median 9.2 [7.2-10.8] years). LVEF improved
      from 33+/-8% to 54+/-6% after beta-blockade (P<0.0001). At the last
      echocardiographic evaluation, 26% of the patients had an LVEF<45% (mean+/-SD:
      34+/-6%), whereas 74% still had an LVEF>=45% (mean+/-SD: 54+/-6%). Independent
      predictors of LVEF deterioration were a low LVEF, a high left ventricular end
      diastolic diameter and a low heart rate after beta-blockade, and the presence of
      a complete left bundle-branch block. In the overall study population, survival
      rates were 90% at 5 years and 75% at 10 years. Cardiovascular death rate was 9%,
      noncardiovascular death rate was 11%, and unknown death rate was 3%. Patients
      with subsequent LVEF deterioration had a higher cardiovascular mortality compared
      with patients with sustained recovered LVEF (22% versus 4%). CONCLUSIONS: The
      long-term survival of patients with LVSD and with near-normal LVEF after beta
      blockade is good. However, a quarter of these patients may experience a
      subsequent degradation of LVEF. These patients are at higher risk of
      cardiovascular mortality.

PMID- 24563450
TI  - Comparative survival and cost-effectiveness of advanced therapies for end-stage
      heart failure.
AB  - BACKGROUND: Treatment options for end-stage heart failure include inotrope
      dependent medical therapy, orthotopic heart transplantation (OHT), left
      ventricular assist device (LVAD) as destination therapy or bridge to transplant.
      METHODS AND RESULTS: We developed a state-transition model to simulate 4
      treatment options and associated morbidity and mortality. Transition
      probabilities, costs, and utilities were estimated from published sources.
      Calculated outcomes included survival, quality-adjusted life-years, and
      incremental cost-effectiveness. Sensitivity analyses were performed on model
      parameters to test robustness. Average life expectancy for OHT-eligible patients
      is estimated at 1.1 years, with 39% surviving to 1 year. OHT with a median wait
      time of 5.6 months is estimated to increase life expectancy to 8.5 years, and
      costs <$100,000/quality-adjusted life-year gained, relative to inotrope-dependent
      medical therapy. Bridge to transplant-LVAD followed by OHT further is estimated
      to increase life expectancy to 12.3 years, for $226,000/quality-adjusted life
      year gained versus OHT. Among OHT-ineligible patients, mean life expectancy with
      inotrope-dependent medical therapy is estimated at 9.4 months, with 26% surviving
      to 1 year. Patients who instead received destination therapy-LVAD are estimated
      to live 4.4 years on average from extrapolation of recent constant hazard rates
      beyond the first year. This strategy costs $202,000/quality-adjusted life-year
      gained, relative to inotrope-dependent medical therapy. Patient's age, time on
      wait list, and costs associated with care influence outcomes. CONCLUSIONS: Under
      most scenarios, OHT prolongs life and is cost effective in eligible patients.
      Bridge to transplant-LVAD is estimated to offer >3.8 additional life-years for
      patients waiting >=6 months, but does not meet conventional cost-effectiveness
      thresholds. Destination therapy-LVAD significantly improves life expectancy in
      OHT-ineligible patients. However, further reductions in adverse events or
      improved quality of life are needed for destination therapy-LVAD to be cost
      effective.

PMID- 24563451
TI  - Prevention is better than cure for emerging infectious diseases.

PMID- 24563452
TI  - Placebo controlled trials.

PMID- 24563453
TI  - Severe accidental hypothermia.

PMID- 24563454
TI  - Hospital admissions for anxiety peak in women over 60, UK study finds.

PMID- 24563455
TI  - People use web to find doctors but prefer personal recommendations, says US
      survey.

PMID- 24563456
TI  - Brief school-based interventions and behavioural outcomes for substance-using
      adolescents.
AB  - BACKGROUND: Adolescent substance use is a major problem, in and of itself and
      because it acts as a risk factor for other problem behaviours. As substance use
      during adolescence can lead to adverse and often long-term health and social
      consequences, it is important to intervene early on in order to prevent
      progression to more severe problems. Brief interventions have been shown to
      reduce problematic substance use among adolescents and are especially useful for
      individuals who have moderately risky patterns of substance use. Such
      interventions can be conducted in school settings. This review set out to
      evaluate the effectiveness of brief school-based interventions for adolescent
      substance use. OBJECTIVES: To evaluate the effectiveness of brief school-based
      interventions on reducing substance use and other behavioural outcomes among
      adolescents compared to another intervention or assessment-only conditions.
      SEARCH METHODS: We searched 10 electronic databases and six websites on evidence
      based interventions, and the reference lists of included studies and reviews,
      from 1966 to March 2013. We also contacted authors and organisations to identify
      any additional studies. SELECTION CRITERIA: We included randomised controlled
      trials that evaluated the effects of brief school-based interventions for
      substance-using adolescents.The primary outcomes were reduction or cessation of
      substance use. The secondary outcomes were engagement in criminal activity and
      engagement in delinquent or problem behaviours related to substance use. DATA
      COLLECTION AND ANALYSIS: We used the standard methodological procedures outlined
      by The Cochrane Collaboration, including the GRADE approach for evaluating the
      quality of evidence. MAIN RESULTS: Six studies involving 1139 participants were
      included in this review. Overall the quality of evidence was moderate in the
      information provision comparison, and low or very low in the assessment only
      comparison. Reasons for downgrading the quality included risk of bias of the
      included studies, imprecision and inconsistency. Our findings suggested that
      compared to information provision only, brief interventions (BIs) did not have a
      significant effect on any substance use (three studies, 732 participants,
      standardised mean difference (SMD) -0.06; 95% confidence interval (CI) -0.20 to
      0.09) or delinquent-type behaviour outcomes among adolescents (two studies, 531
      participants, SMD -0.26; 95% CI -0.54 to 0.02). When compared to assessment-only
      controls, BIs had some significant effects on substance use and delinquent-type
      or problem behaviours, but high levels of heterogeneity existed between studies
      and it was not always possible to pool the results. When the comparison was with
      assessment-only conditions, studies of individual interventions that measured BI
      effectiveness reported significantly reduced substance use in general and in two
      studies reduced frequency of alcohol use specifically. When the data were pooled,
      BIs reduced cannabis frequency (SMD -0.22; 95% CI -0.45 to -0.02) across three
      studies (n = 407). Cannabis quantity was also reduced by BIs in comparison to
      assessment only (SMD -60.27; 95% CI -66.59 to -53.95) in one study (n = 179).
      However, the evidence for studies that compared brief interventions to assessment
      only conditions was generally of low quality. Brief interventions also had mixed
      effects on participants' delinquent or problem behaviours. AUTHORS' CONCLUSIONS:
      There was limited quality evidence that brief school-based interventions were
      more effective in reducing substance use than the assessment-only condition, but
      were similar to information provision. There is some evidence for the
      effectiveness of BI in reducing adolescent substance use, particularly cannabis,
      when compared to assessment only. However, it is premature to make definitive
      statements about the effectiveness of brief school-based interventions for
      reducing adolescent substance use. Further high quality studies examining the
      relative effectiveness of BIs for substance use and other problem behaviours need
      to be conducted, particularly in low- and middle-income countries.

PMID- 24563458
TI  - Nkx2-5 suppresses the proliferation of atrial myocytes and conduction system.
AB  - RATIONALE: Tight control of cardiomyocyte proliferation is essential for the
      formation of four-chambered heart. Although human mutation of NKX2-5 is linked to
      septal defects and atrioventricular conduction abnormalities, early lethality and
      hemodynamic alteration in the mutant models have caused controversy as to whether
      Nkx2-5 regulates cardiomyocyte proliferation. OBJECTIVE: In this study, we
      circumvented these limitations by atrial-restricted deletion of Nkx2-5. METHOD
      AND RESULTS: Atrial-specific Nkx2-5 mutants died shortly after birth with
      hyperplastic working myocytes and conduction system including two nodes and
      internodal tracts. Multicolor reporter analysis revealed that Nkx2-5-null
      cardiomyocytes displayed clonal proliferative activity throughout the atria,
      indicating the suppressive role of Nkx2-5 in cardiomyocyte proliferation after
      chamber ballooning stages. Transcriptome analysis revealed that aberrant
      activation of Notch signaling underlies hyperproliferation of mutant
      cardiomyocytes, and forced activation of Notch signaling recapitulates
      hyperproliferation of working myocytes but not the conduction system.
      CONCLUSIONS: Collectively, these data suggest that Nkx2-5 regulates the
      proliferation of atrial working and conduction myocardium in coordination with
      Notch pathway.

PMID- 24563459
TI  - Laparoscopy for diagnosing resectability of disease in patients with advanced
      ovarian cancer.
AB  - BACKGROUND: The presence of residual tumour after primary debulking surgery is
      the most important prognostic factor in patients with advanced ovarian cancer. In
      up to 60% of cases, residual tumour of more than 1 cm is left behind, stressing
      the necessity of accurately selecting those patients who should be treated with
      primary debulking surgery and those who should receive neoadjuvant chemotherapy
      instead. OBJECTIVES: To determine if performing an open laparoscopy after the
      diagnostic work-up of patients suspected of advanced ovarian cancer is accurate
      in predicting the resectability of disease. SEARCH METHODS: We searched MEDLINE,
      EMBASE, The Cochrane Central Register of Controlled Trials (CENTRAL), the
      Cochrane Register of Diagnostic Test Accuracy Studies, MEDION and ISI Web of
      Science to February 2013. Furthermore, we checked references of identified
      primary studies and review articles. SELECTION CRITERIA: We included studies that
      evaluated the diagnostic accuracy of laparoscopy to determine the resectability
      of disease in patients who are suspected of advanced ovarian cancer and planned
      to receive primary debulking surgery. DATA COLLECTION AND ANALYSIS: Two review
      authors assessed the quality of included studies using QUADAS-2 and extracted
      data on study and patients' characteristics, index test, target condition and
      reference standard. Data for two-by-two tables were extracted and summarised
      graphically. Sensitivity and specificity and negative predictive values were
      calculated. MAIN RESULTS: We included seven studies reporting on six cohorts.
      Between 27% to 64% of included patients per study were positive on laparoscopy
      (too extensive disease to warrant laparotomy) and between 36% to 73% were
      negative (disease suitable for debulking laparotomy). Only two studies avoided
      partial verification bias and provided data to calculate sensitivity and
      specificity, which did not justify meta-analysis. These two studies had a
      sensitivity of 0.70 (95% confidence interval (CI) 0.57 to 0.82) and 0.71 (95% CI
      0.44 to 0.90); however, the specificity of both studies was 1.00 (95% CI 0.90 to
      1.00). In these two studies there were no false positives, i.e. no patients for
      whom laparoscopy indicated that major surgery would not be successful and should
      be avoided, whereas, in reality the patient could be successfully operated upon.
      Negative predictive values (NPV), for those patients who were diagnosed with
      having not too extensive disease correctly identified were 0.75 (95% CI 0.55 to
      0.86) and 0.96 (95% CI 0.56 to 0.99) due to a different prevalence. Although the
      studies did report sufficient data to calculate NPVs, we judged these estimates
      too heterogeneous to meta-analyse.Three studies described the development or
      validation of a prediction model with a clear cut-off for test positivity.
      Sensitivity and specificity of these prediction models were 0.30 to 0.70 and 0.89
      to 1.00, respectively. However, one of these studies suffered from partial
      verification bias. AUTHORS' CONCLUSIONS: Laparoscopy is a promising test, but the
      low number of studies and the differences between the included studies do not
      allow firm conclusions to be drawn from these data. Due to a difference in
      prevalence, there is a wide range in negative predictive values between studies.
      Two studies verified all patients. These imply a high specificity of laparoscopy
      in diagnosing resectability and have a good sensitivity. Both studies show that
      the use of criteria for unresectable disease will result in no patients
      inappropriately unexplored. However, there will still be patients undergoing
      unsuccessful primary laparotomy. Using a prediction model does not increase the
      sensitivity and will result in more unnecessarily explored patients, due to a
      lower specificity.

PMID- 24563457
TI  - Divergent regulation of ryanodine receptor 2 calcium release channels by
      arrhythmogenic human calmodulin missense mutants.
AB  - RATIONALE: Calmodulin (CaM) mutations are associated with an autosomal dominant
      syndrome of ventricular arrhythmia and sudden death that can present with
      divergent clinical features of catecholaminergic polymorphic ventricular
      tachycardia (CPVT) or long QT syndrome (LQTS). CaM binds to and inhibits
      ryanodine receptor (RyR2) Ca release channels in the heart, but whether
      arrhythmogenic CaM mutants alter RyR2 function is not known. OBJECTIVE: To gain
      mechanistic insight into how human CaM mutations affect RyR2 Ca channels. METHODS
      AND RESULTS: We studied recombinant CaM mutants associated with CPVT (N54I and
      N98S) or LQTS (D96V, D130G, and F142L). As a group, all LQTS-associated CaM
      mutants (LQTS-CaMs) exhibited reduced Ca affinity, whereas CPVT-associated CaM
      mutants (CPVT-CaMs) had either normal or modestly lower Ca affinity. In
      permeabilized ventricular myocytes, CPVT-CaMs at a physiological intracellular
      concentration (100 nmol/L) promoted significantly higher spontaneous Ca wave and
      spark activity, a typical cellular phenotype of CPVT. Compared with wild-type
      CaM, CPVT-CaMs caused greater RyR2 single-channel open probability and showed
      enhanced binding affinity to RyR2. Even a 1:8 mixture of CPVT-CaM:wild-type-CaM
      activated Ca waves, demonstrating functional dominance. In contrast, LQTS-CaMs
      did not promote Ca waves and exhibited either normal regulation of RyR2 single
      channels (D96V) or lower RyR2-binding affinity (D130G and F142L). None of the CaM
      mutants altered Ca/CaM binding to CaM-kinase II. CONCLUSIONS: A small proportion
      of CPVT-CaM is sufficient to evoke arrhythmogenic Ca disturbances, whereas LQTS
      CaMs do not. Our findings explain the clinical presentation and autosomal
      dominant inheritance of CPVT-CaM mutations and suggest that RyR2 interactions are
      unlikely to explain arrhythmogenicity of LQTS-CaM mutations.

PMID- 24563460
TI  - Oxidation of endogenous N-arachidonoylserotonin by human cytochrome P450 2U1.
AB  - Cytochrome P450 (P450) 2U1 has been shown to be expressed, at the mRNA level, in
      human thymus, brain, and several other tissues. Recombinant P450 2U1 was purified
      and used as a reagent in a metabolomic search for substrates in bovine brain. In
      addition to fatty acid oxidation reactions, an oxidation of endogenous N
      arachidonoylserotonin was characterized. Subsequent NMR and mass spectrometry and
      chemical synthesis showed that the main product was the result of C-2 oxidation
      of the indole ring, in contrast to other human P450s that generated different
      products. N-Arachidonoylserotonin, first synthesized chemically and described as
      an inhibitor of fatty acid amide hydrolase, had previously been found in porcine
      and mouse intestine; we demonstrated its presence in bovine and human brain
      samples. The product (2-oxo) was 4-fold less active than N-arachidonoylserotonin
      in inhibiting fatty acid amide hydrolase. The rate of oxidation of N
      arachidonoylserotonin was similar to that of arachidonic acid, one of the
      previously identified fatty acid substrates of P450 2U1. The demonstration of the
      oxidation of N-arachidonoylserotonin by P450 2U1 suggests a possible role in
      human brain and possibly other sites. 

PMID- 24563461
TI  - The acidic C-terminal tail of the GyrA subunit moderates the DNA supercoiling
      activity of Bacillus subtilis gyrase.
AB  - Gyrase is a type II DNA topoisomerase that introduces negative supercoils into
      DNA in an ATP-dependent reaction. It consists of a topoisomerase core, formed by
      the N-terminal domains of the two GyrA subunits and by the two GyrB subunits,
      that catalyzes double-stranded DNA cleavage and passage of a second double
      stranded DNA through the gap in the first. The C-terminal domains (CTDs) of the
      GyrA subunits form a beta-pinwheel and bind DNA around their positively charged
      perimeter. As a result, DNA is bound as a positive supercoil that is converted
      into a negative supercoil by strand passage. The CTDs contain a conserved 7-amino
      acid motif that connects blades 1 and 6 of the beta-pinwheel and is a hallmark
      feature of gyrases. Deletion of this so-called GyrA-box abrogates DNA bending by
      the CTDs and DNA-induced narrowing of the N-gate, affects T-segment presentation,
      reduces the coupling of DNA binding to ATP hydrolysis, and leads to supercoiling
      deficiency. Recently, a severe loss of supercoiling activity of Escherichia coli
      gyrase upon deletion of the non-conserved acidic C-terminal tail (C-tail) of the
      CTDs has been reported. We show here that, in contrast to E. coli gyrase, the C
      tail is a very moderate negative regulator of Bacillus subtilis gyrase activity.
      The C-tail reduces the degree of DNA bending by the CTDs but has no effect on DNA
      induced conformational changes of gyrase that precede strand passage and reduces
      DNA-stimulated ATPase and DNA supercoiling activities only 2-fold. Our results
      are in agreement with species-specific, differential regulatory effects of the C
      tail in gyrases from different organisms. 

PMID- 24563462
TI  - Trans-activation response (TAR) RNA-binding protein 2 is a novel modulator of
      transient receptor potential canonical 4 (TRPC4) protein.
AB  - TRPC4 proteins function as Ca(2+) conducting, non-selective cation channels in
      endothelial, smooth muscle, and neuronal cells. To further characterize the roles
      of TRPC4 in vivo, detailed information about the molecular composition of native
      channel complexes and their association with cellular signaling networks is
      needed. Therefore, a mouse brain cDNA library was searched for novel TRPC4
      interacting proteins using a modified yeast two-hybrid assay. This screen
      identified Trans-activation Response RNA-binding protein 2 (Tarpb2), a protein
      that recruits the Dicer complex to Ago2 for microRNA processing and gene
      silencing. Tarbp2 was found to bind to the C terminus of TRPC4 and TRPC5 and to
      modulate agonist-dependent TRPC4-induced Ca(2+) entry. A stretch of basic
      residues within the Tarbp2 protein is required for these actions. Tarbp2 binding
      to and modulation of TRPC4 occurs in the presence of endogenously expressed Dicer
      but is no longer detectable when the Dicer cDNA is overexpressed. Dicer activity
      in crude cell lysates is increased in the presence of Ca(2+), most probably by
      Ca(2+)-dependent proteolytic activation of Dicer. Apparently, Tarbp2 binding to
      TRPC4 promotes changes of cytosolic Ca(2+) and, thereby, leads to a dynamic
      regulation of Dicer activity, essentially at low endogenous Dicer concentrations.

PMID- 24563463
TI  - Menin is required for optimal processing of the microRNA let-7a.
AB  - Multiple endocrine neoplasia type I (MEN1) is an inherited syndrome that includes
      susceptibility to pancreatic islet hyperplasia. This syndrome results from
      mutations in the MEN1 gene, which encodes menin protein. Menin interacts with
      several transcription factors, including JunD, and inhibits their activities.
      However, the precise mechanism by which menin suppresses gene expression is not
      well understood. Here, we show that menin interacts with arsenite-resistant
      protein 2 (ARS2), a component of the nuclear RNA CAP-binding complex that is
      crucial for biogenesis of certain miRNAs including let-7a. The levels of primary
      let-7a (pri-let-7a) are not affected by menin; however, the levels of mature let
      7a are substantially decreased upon Men1 excision. Let-7a targets, including Insr
      and Irs2, pro-proliferative genes that are crucial for insulin-mediated
      signaling, are up-regulated in Men1-excised cells. Inhibition of let-7a using
      anti-miRNA in wild type cells is sufficient to enhance the expression of insulin
      receptor substrate 2 (IRS2) to levels observed in Men1-excised cells. Depletion
      of menin does not affect the expression of Drosha and CBP80, but substantially
      impairs the processing of pri-miRNA to pre-miRNA. Ars2 knockdown decreased let-7a
      processing in menin-expressing cells but had little impact on let-7a levels in
      menin-excised cells. As IRS2 is known to mediate insulin signaling and
      insulin/mitogen-induced cell proliferation, these findings collectively unravel a
      novel mechanism whereby menin suppresses cell proliferation, at least partly by
      promoting the processing of certain miRNAs, including let-7a, leading to
      suppression of Irs2 expression and insulin signaling. 

PMID- 24563464
TI  - Human immunodeficiency virus type 1 enhancer-binding protein 3 is essential for
      the expression of asparagine-linked glycosylation 2 in the regulation of
      osteoblast and chondrocyte differentiation.
AB  - Human immunodeficiency virus type 1 enhancer-binding protein 3 (Hivep3)
      suppresses osteoblast differentiation by inducing proteasomal degradation of the
      osteogenesis master regulator Runx2. In this study, we tested the possibility of
      cooperation of Hivep1, Hivep2, and Hivep3 in osteoblast and/or chondrocyte
      differentiation. Microarray analyses with ST-2 bone stroma cells demonstrated
      that expression of any known osteochondrogenesis-related genes was not commonly
      affected by the three Hivep siRNAs. Only Hivep3 siRNA promoted osteoblast
      differentiation in ST-2 cells, whereas all three siRNAs cooperatively suppressed
      differentiation in ATDC5 chondrocytes. We further used microarray analysis to
      identify genes commonly down-regulated in both MC3T3-E1 osteoblasts and ST-2
      cells upon knockdown of Hivep3 and identified asparagine-linked glycosylation 2
      (Alg2), which encodes a mannosyltransferase residing on the endoplasmic
      reticulum. The Hivep3 siRNA-mediated promotion of osteoblast differentiation was
      negated by forced Alg2 expression. Alg2 suppressed osteoblast differentiation and
      bone formation in cultured calvarial bone. Alg2 was immunoprecipitated with
      Runx2, whereas the combined transfection of Runx2 and Alg2 interfered with Runx2
      nuclear localization, which resulted in suppression of Runx2 activity.
      Chondrocyte differentiation was promoted by Hivep3 overexpression, in concert
      with increased expression of Creb3l2, whose gene product is the endoplasmic
      reticulum stress transducer crucial for chondrogenesis. Alg2 silencing suppressed
      Creb3l2 expression and chondrogenesis of ATDC5 cells, whereas infection of Alg2
      expressing virus promoted chondrocyte maturation in cultured cartilage rudiments.
      Thus, Alg2, as a downstream mediator of Hivep3, suppresses osteogenesis, whereas
      it promotes chondrogenesis. To our knowledge, this study is the first to link a
      mannosyltransferase gene to osteochondrogenesis. 

PMID- 24563466
TI  - Cross-talk between two essential nutrient-sensitive enzymes: O-GlcNAc transferase
      (OGT) and AMP-activated protein kinase (AMPK).
AB  - Nutrient-sensitive pathways regulate both O-GlcNAc transferase (OGT) and AMP
      activated protein kinase (AMPK), cooperatively connecting metabolic homeostasis
      to regulation of numerous intracellular processes essential for life. Similar to
      phosphorylation, catalyzed by kinases such as AMPK, O-GlcNAcylation is a highly
      dynamic Ser/Thr-specific post-translational modification of nuclear, cytoplasmic,
      and mitochondrial proteins catalyzed exclusively by OGT. OGT and AMPK target a
      multitude of intracellular proteins, with the net effect to protect cells from
      the damaging effects of metabolic stress. Despite hundreds of studies
      demonstrating significant overlap in upstream and downstream signaling processes,
      no study has investigated if OGT and AMPK can directly regulate each other. We
      show acute activation of AMPK alters the substrate selectivity of OGT in several
      cell lines and nuclear localization of OGT in C2C12 skeletal muscle myotubes.
      Nuclear localization of OGT affects O-GlcNAcylation of numerous nuclear proteins
      and acetylation of Lys-9 on histone 3 in myotubes. AMPK phosphorylates Thr-444 on
      OGT in vitro; phosphorylation of Thr-444 is tightly associated with AMPK activity
      and nuclear localization of OGT in myotubes, and phospho-mimetic T444E-OGT
      exhibits altered substrate selectivity. Conversely, the alpha- and gamma-subunits
      of AMPK are O-GlcNAcylated, O-GlcNAcylation of the gamma1-subunit increases with
      AMPK activity, and acute inhibition of O-GlcNAc cycling disrupts activation of
      AMPK. We have demonstrated significant cross-talk between the O-GlcNAc and AMPK
      systems, suggesting OGT and AMPK may cooperatively regulate nutrient-sensitive
      intracellular processes that mediate cellular metabolism, growth, proliferation,
      and/or tissue function. 

PMID- 24563465
TI  - Yeast Pah1p phosphatidate phosphatase is regulated by proteasome-mediated
      degradation.
AB  - Yeast PAH1-encoded phosphatidate phosphatase is the enzyme responsible for the
      production of the diacylglycerol used for the synthesis of triacylglycerol that
      accumulates in the stationary phase of growth. Paradoxically, the growth phase
      mediated inductions of PAH1 and phosphatidate phosphatase activity do not
      correlate with the amount of Pah1p; enzyme abundance declined in a growth phase
      dependent manner. Pah1p from exponential phase cells was a relatively stable
      protein, and its abundance was not affected by incubation with an extract from
      stationary phase cells. Recombinant Pah1p was degraded upon incubation with the
      100,000 * g pellet fraction of stationary phase cells, although the enzyme was
      stable when incubated with the same fraction of exponential phase cells. MG132,
      an inhibitor of proteasome function, prevented degradation of the recombinant
      enzyme. Endogenously expressed and plasmid-mediated overexpressed levels of Pah1p
      were more abundant in the stationary phase of cells treated with MG132. Pah1p was
      stabilized in mutants with impaired proteasome (rpn4Delta, blm10Delta, ump1Delta,
      and pre1 pre2) and ubiquitination (hrd1Delta, ubc4Delta, ubc7Delta, ubc8Delta,
      and doa4Delta) functions. The pre1 pre2 mutations that eliminate nearly all
      chymotrypsin-like activity of the 20 S proteasome had the greatest stabilizing
      effect on enzyme levels. Taken together, these results supported the conclusion
      that Pah1p is subject to proteasome-mediated degradation in the stationary phase.
      That Pah1p abundance was stabilized in pah1Delta mutant cells expressing
      catalytically inactive forms of Pah1p and dgk1Delta mutant cells with induced
      expression of DGK1-encoded diacylglycerol kinase indicated that alteration in
      phosphatidate and/or diacylglycerol levels might be the signal that triggers
      Pah1p degradation. 

PMID- 24563467
TI  - Oligomerization-induced conformational change in the C-terminal region of Nel
      like molecule 1 (NELL1) protein is necessary for the efficient mediation of
      murine MC3T3-E1 cell adhesion and spreading.
AB  - NELL1 is a large oligomeric secretory glycoprotein that functions as an
      osteoinductive factor. NELL1 contains several conserved domains, has structural
      similarities to thrombospondin 1, and supports osteoblastic cell adhesion through
      integrins. To define the structural requirements for NELL1-mediated cell
      adhesion, we prepared a series of recombinant NELL1 proteins (intact, deleted,
      and cysteine-mutant) from a mammalian expression system and tested their
      activities. A deletion analysis demonstrated that the C-terminal cysteine-rich
      region of NELL1 is critical for the cell adhesion activity of NELL1. Reducing
      agent treatment decreased the cell adhesion activity of full-length NELL1 but not
      of its C-terminal fragments, suggesting that the intramolecular disulfide bonds
      within this region are not functionally necessary but that other disulfide
      linkages in the N-terminal region of NELL1 may be involved in cell adhesion
      activity. By replacing cysteine residues with serines around the coiled-coil
      domain of NELL1, which is responsible for oligomerization, we created a mutant
      NELL1 protein that was unable to form homo-oligomers, and this monomeric mutant
      showed substantially lower cell adhesion activity than intact NELL1. These
      results suggest that an oligomerization-induced conformational change in the C
      terminal region of NELL1 is important for the efficient mediation of cell
      adhesion and spreading by NELL1. 

PMID- 24563468
TI  - Metal protein attenuating compounds for the treatment of Alzheimer's dementia.
AB  - BACKGROUND: Alzheimer's dementia (AD) may be caused by the formation of
      extracellular senile plaques comprised of beta-amyloid (Abeta). In vitro and
      mouse model studies have demonstrated that metal protein attenuating compounds
      (MPACs) promote the solubilisation and clearance of Abeta. OBJECTIVES: To
      evaluate the efficacy of metal protein attenuating compounds (MPACs) for the
      treatment of cognitive impairment due to Alzheimer's dementia. SEARCH METHODS: We
      searched ALOIS, the Cochrane Dementia and Cognitive Improvement Group Specialized
      Register, on 29 July 2010 using the terms: Clioquinol OR PBT1 OR PBT2 OR "metal
      protein" OR MPACS OR MPAC. SELECTION CRITERIA: Randomised double-blind trials in
      which treatment with an MPAC was administered to participants with Alzheimer's
      dementia in a parallel group comparison with placebo were included. DATA
      COLLECTION AND ANALYSIS: Three review authors (RM, LJ, ELS) independently
      assessed the quality of trials according to the Cochrane Handbook for Systematic
      Reviews of Interventions.The primary outcome measure of interest was cognitive
      function (as measured by psychometric tests). The secondary outcome measures of
      interest were in the following areas: quality of life, functional performance,
      effect on carer, biomarkers, safety and adverse effects, and death. MAIN RESULTS:
      Two MPAC trials were identified. One trial compared clioquinol (PBT1) with
      placebo in 36 patients and 32 had sufficient data for per protocol analysis.
      There was no statistically significant difference in cognition (as measured on
      the Alzheimer's Disease Assessment Scale - Cognition (ADAS-Cog)) between the
      active treatment and placebo groups at 36 weeks. The difference in mean change
      from baseline ADAS-Cog score in the clioquinol arm compared with the placebo arm
      at weeks 24 and 36 was a difference of 7.37 (95% confidence interval (CI) 1.51 to
      13.24) and 6.36 (95% CI -0.50 to 13.23), respectively.There was no significant
      impact on non-cognitive symptoms or clinical global impression. One participant
      in the active treatment group developed neurological symptoms (impaired visual
      acuity and colour vision) which resolved on cessation of treatment and were
      possibly attributable to the drug.In the second trial a successor compound, PBT2,
      was compared with placebo in 78 participants with mild Alzheimer's dementia; all
      were included in the intention-to-treat analysis. There was no significant
      difference in the Neuropsychological Test Battery (NTB) composite or memory
      between placebo and PBT2 in the least squares mean change from baseline at week
      12. However, two executive function component tests of the NTB showed significant
      improvement over placebo in the PBT2 250 mg group from baseline to week 12:
      category fluency test (2.8 words, 95% CI 0.1 to 5.4; P = 0.041) and trail making
      part B (-48.0 s, 95% CI -83.0 to -13.0; P = 0.009). In the executive factor Z
      score, the difference in least squares mean change from baseline at week 12 for
      PBT2 250 mg compared with placebo was 0.27 (0.01 to 0.53; p=0.042).There was no
      significant effect on cognition on Mini-Mental State Examination (MMSE) or ADAS
      Cog scales. PBT2 had a favourable safety profile. AUTHORS' CONCLUSIONS: There is
      an absence of evidence as to whether clioquinol (PBT1) has any positive clinical
      benefit for patients with AD, or whether the drug is safe. We have some concerns
      about the quality of the study methodology; there was an imbalance in treatment
      and control groups after randomisation (participants in the active treatment
      group had a higher mean pre-morbid IQ) and the secondary analyses of results
      stratified by baseline dementia severity. The planned phase III trial of PBT1 has
      been abandoned and this compound has been withdrawn from development. The second
      trial of PBT2 was more rigorously conducted and showed that after 12 weeks this
      compound appeared to be safe and well tolerated in people with mild Alzheimer's
      dementia. Larger trials are now required to demonstrate cognitive efficacy.

PMID- 24563469
TI  - Left ventricular structure and function in transthyretin-related versus light
      chain cardiac amyloidosis.
AB  - BACKGROUND: Immunoglobulin amyloid light-chain (AL)-related cardiac amyloidosis
      (CA) has a worse prognosis than either wild-type (ATTRwt) or mutant (ATTRm)
      transthyretin (TTR) CA. Detailed echocardiographic studies have been performed in
      AL amyloidosis but not in TTR amyloidosis and might give insight into this
      difference. We assessed cardiac structure and function and outcome in a large
      population of patients with CA and compared findings in TTR and AL-related
      disease. METHODS AND RESULTS: We analyzed 172 patients with CA (AL amyloidosis,
      n=80; ATTRm, n=36; ATTRwt, n=56) by standard echocardiography and 2-dimensional
      speckle-tracking imaging-derived left ventricular (LV) longitudinal (LS), radial,
      and circumferential strains. Despite a preserved LV ejection fraction (55+/-12%),
      LS was severely impaired in CA. Standard measures of LV function and speckle
      tracking imaging worsened as wall thickness increased, whereas apical LS was
      preserved regardless of the pathogenesis of CA and the degree of wall thickening.
      Compared with ATTRm and AL amyloidosis, ATTRwt was characterized by greater LV
      wall thickness and lower ejection fraction. LS was more depressed in both ATTRwt
      and AL amyloidosis (-11+/-3% and -12+/-4%, respectively, P=0.54) than in ATTRm (
      15+/-4%, P<0.01 versus AL amyloidosis and ATTRwt). TTR-related causes were
      favorable predictors of survival, whereas LS and advanced New York Heart
      Association class were negative predictors. CONCLUSIONS: In patients with CA,
      worsening LV function correlated with increasing wall thickness regardless of
      pathogenesis. Patients with ATTRwt had a statistically greater wall thickness but
      lesser mortality than those with AL amyloidosis, despite very similar degrees of
      LS impairment. This paradox suggests an additional mechanism for LV dysfunction
      in AL amyloidosis, such as previously demonstrated light-chain toxicity.

PMID- 24563471
TI  - Anti-N-methyl-D-aspartate (anti-NMDA) receptor antibody encephalitis in a male
      adolescent with a large mediastinal teratoma.
AB  - We present a case of a 16-year-old boy with Klinefelter syndrome who presented
      with a syndrome of impaired alertness, orofacial dyskinesias, choreiform
      movements, epileptic seizures, and autonomic instability, pointing to a diagnosis
      of anti-N-methyl-Daspartate (anti-NMDA) receptor antibody encephalitis. 

PMID- 24563470
TI  - Longitudinally extensive optic neuritis in pediatric patients.
AB  - Extensive optic nerve demyelinating lesions on magnetic resonance imaging (MRI)
      in adults could indicate a diagnosis other than multiple sclerosis with worse
      prognosis such as neuromyelitis optica. We report the frequency of longitudinally
      extensive lesions in children with first events of optic neuritis. Subjects had
      brain or orbit MRI within 3 months of onset and were evaluated at the University
      of California, San Francisco, Pediatric Multiple Sclerosis Center. Lesion length,
      determined by T2 hyperintensity or contrast enhancement, was blindly graded as
      absent, focal or longitudinally extensive (at least 2 contiguous segments of
      optic nerve). Of 25 subjects, 9 (36%) had longitudinally extensive optic
      neuritis. Extensive lesions were not associated with non-multiple sclerosis
      versus multiple sclerosis diagnosis (P = 1.00). No association between age and
      lesion extent was observed (P = .26). Prospective studies are needed to determine
      if longitudinally extensive optic neuritis can predict visual outcome. 

PMID- 24563472
TI  - Congenital dermal sinus tract of the spine: experience of 16 patients.
AB  - Congenital dermal sinus tract is a rare entity which lined by epithelial cells
      and can end anywhere between subcutaneous planes to thecal sac. These tracts may
      be accompanied with other pathologies such as lipomyelomeningocele,
      myelomeningocele, split cord malformation, tethered cord, filum abnormality and
      inclusion tumors and treatment includes resection of tract with intradural
      exploration. The authors review their experience with 16 cases. Clinical,
      radiological appearance and treatment of these lesions discussed with literature
      review. 

PMID- 24563473
TI  - Anti-N-methyl-d-aspartate (Anti-NMDA) receptor encephalitis: rapid and sustained
      clinical improvement with steroid therapy starting in the late phase.
AB  - Anti-N-methyl-d-aspartate (anti-NMDA) receptor encephalitis is an
      autoimmune/paraneoplastic encephalitis, with neurologic and psychiatric symptoms.
      Early and aggressive therapy has been shown to improve prognosis although
      problems with executive functions and memory have continued for several years. A
      15-year-old girl had a history of initial symptoms including behavioral
      difficulties, poor attention, and frequent seizures progressing to a catatonia
      like state, 2.5 months after onset of initial symptoms. Anti-NMDA receptor
      antibodies were detected in serum and cerebrospinal fluid. Subsequent to
      treatment with methylprednisolone starting 3 months after onset, motor skills,
      responsiveness, self-care, and speech improved rapidly. Her neuropsychologica
      profile assessed after 2 months showed global difficulties predominantly in
      attention, executive functions, memory, and visual perception, which moderately
      recovered in the 7th and 24th months, respectively. Contrary to current
      literature supporting the positive impact of early immunomodulatory therapy, a
      dramatic resolution of major neurologic and psychiatric symptoms was detected
      with steroid treatment given in the late phase. 

PMID- 24563474
TI  - Extrapontine myelinolysis in an 18-month-old boy with diabetic ketoacidosis: case
      report and literature review.
AB  - Extrapontine myelinolysis is characterized by symmetric demyelination following
      rapid shifts in serum osmolality in the supratentorial compartment. Extrapontine
      myelinolysis in children is rare compared to adults. The most common underlying
      pathophysiology is rapid correction of hyponatremia. Only 2 cases were published
      after diabetic ketoacidosis without electrolyte imbalance in the English
      literature. This study presents an unusual and possibly the youngest case of
      extrapontine myelinolysis that occurred in the setting of diabetic ketoacidosis
      and complicated cerebral edema without electrolyte imbalance, along with a review
      of the literature. 

PMID- 24563475
TI  - Detection of intragenic SMN1 mutations in spinal muscular atrophy patients with a
      single copy of SMN1.
AB  - Proximal spinal muscular atrophy is an autosomal recessive disorder characterized
      by symmetrical muscle weakness due to degeneration of alpha motor neurons in the
      spinal cord. Homozygous deletions in the SMN1 have been reported in more than 90%
      of spinal muscular atrophy cases. Compound heterozygous patients account for
      approximately 4% of spinal muscular atrophy cases. In this study, we performed a
      quantitative test in 20 of 87 spinal muscular atrophy patients who did not have
      homozygous deletion of SMN1. Mutation screening of SMN1 gene was performed in 4
      patients who have only 1 copy of SMN1 to identify intragenic mutations. In
      addition to a previously described missense mutation in exon 4 (p.A188S/
      c.562G>T), we identified 2 novel mutations including a single nucleotide
      insertion in exon 7 (c.861_862insT/p.R288X) and a deletion of nucleotide G in
      exon 3 (c.286delG/p.D96Tfs*53). Our results suggested that about 4% of spinal
      muscular atrophy patients have subtle mutations and might be considered in
      laboratory examination. 

PMID- 24563476
TI  - Fetal alcohol syndrome and secondary schizophrenia: a unique neuropathologic
      study.
AB  - We report the unique neuropathologic study of an adult brain of a patient with
      fetal alcohol syndrome who developed the well-recognized complication of
      schizophrenia in adolescence. The major finding was asymmetric formation of the
      lateral temporal lobes, with marked enlargement of the right superior temporal
      gyrus, suggesting that alcohol is preferentially toxic to temporal lobe
      patterning during gestation. Critical maturational changes unique to adolescence
      can unmask psychotic symptomatology mediated by temporal lobe pathology that has
      been clinically dormant since birth. Elucidating the neuropathologic basis of the
      secondary psychiatric disorders in fetal alcohol syndrome can help provide
      insight into their putative developmental origins. 

PMID- 24563477
TI  - Toe walking in autism: further observations.
AB  - Toe walking has been associated with language disorders and autism. To better
      understand the association between persistent toe walking and sensory and motor
      variables in children with autism, the degree of toe walking was compared with an
      estimate of the severity of sensory integration dysfunction symptoms and the
      presence of residual components of the tonic labyrinthine in supine reflex
      pattern in 61 children younger than 37 months of age with newly diagnosed autism.
      There was no association between the presence of toe walking and sensory symptoms
      (P = .5298) or language age (P = .6142), but there was an association between toe
      walking and the presence of components of the tonic labyrinthine reflex (P =
      .04222). These preliminary results support the contribution of subtle motor
      deficits to the evolution of some behaviors associated with autism. 

PMID- 24563478
TI  - The prediction of later neurodevelopmental status of preterm infants at ages 7 to
      10 years using the Bayley Infant Neurodevelopmental Screener.
AB  - The aim of this study was to see whether the scores of the Bayley Infant
      Neurodevelopmental Screener of 45 high-risk preterm infants (gestational age 26
      37 wk) between the ages of 3 and 24 months predicted neurodevelopmental status at
      7 to 10 years of age. Neurodevelopmental status of 45/122 preterm infants,
      grouped according to their gestational ages of 26 to 29, 30 to 32, and 33 to 37
      weeks, were previously evaluated by Bayley Infant Neurodevelopmental Screener.
      The scores were categorized as low or high-moderate. Verbal and performance
      scores of Wechsler Intelligence Scale for Children-Revised (WISC-R) of those
      patients were assessed between 7 and 10 years. The patients with high-moderate
      risk scores of Bayley Infant Neurodevelopmental Screener at all times, regardless
      of their gestational age, had lower performance, verbal, and total scores of WISC
      R than those of who had low Bayley Infant Neurodevelopmental Screener risk
      scores. High-moderate risk score of Bayley Infant Neurodevelopmental Screener at
      7 to 10, and 16 to 20 months, of all patients especially showed good prediction
      for identifying lower verbal and performance scales. For 7 to 10 months, verbal
      scale: positive predictive value = 92.3%, negative predictive value = 44.4%,
      sensitivity = 70.58%, and specificity = 80%; performance scale: positive
      predictive value = 100%, negative predictive value = 30%, sensitivity = 68.18%,
      and specificity = 100%. For 16 to 20 months, verbal scale: positive predictive
      value = 90%, negative predictive value = 37.5%, sensitivity = 64.3%, and
      specificity = 80%; performance scale: positive predictive value = 90%, negative
      predictive value = 12.5%, sensitivity = 56.3%, and specificity = 50%. Bayley
      Infant Neurodevelopmental Screener shows good prediction of later verbal and
      performance scores of Wechsler Intelligence Scale-Revised for Children as early
      as 7 to 10 months, which gives us the opportunity to start early intervention. 

PMID- 24563479
TI  - A phase I/II, multiple-dose, dose-escalation study of siltuximab, an anti
      interleukin-6 monoclonal antibody, in patients with advanced solid tumors.
AB  - PURPOSE: This phase I/II study evaluated safety, efficacy, and pharmacokinetics
      of escalating, multiple doses of siltuximab, a chimeric anti-interleukin (IL)-6
      monoclonal antibody derived from a new Chinese hamster ovary (CHO) cell line in
      patients with advanced/refractory solid tumors. EXPERIMENTAL DESIGN: In the phase
      I dose-escalation cohorts, 20 patients with advanced/refractory solid tumors
      received siltuximab 2.8 or 5.5 mg/kg every 2 weeks or 11 or 15 mg/kg every 3
      weeks intravenously (i.v.). In the phase I expansion (n = 24) and phase II
      cohorts (n = 40), patients with Kirsten rat sarcoma-2 (KRAS)-mutant tumors,
      ovarian, pancreatic, or anti-EGF receptor (EGFR) refractory/resistant non-small
      cell lung cancer (NSCLC), colorectal, or H&N cancer received 15 mg/kg every 3
      weeks. The phase II primary efficacy endpoint was complete response, partial
      response, or stable disease >6 weeks. RESULTS: Eighty-four patients (35
      colorectal, 29 ovarian, 9 pancreatic, and 11 other) received a median of three
      (range, 1-45) cycles. One dose-limiting toxicity occurred at 5.5 mg/kg. Common
      grade >=3 adverse events were hepatic function abnormalities (15%), physical
      health deterioration (12%), and fatigue (11%). Ten percent of patients had
      siltuximab-related grade >=3 adverse events. Neutropenia (4%) was the only
      possibly related adverse event grade >=3 reported in >1 patient. Serious adverse
      events were reported in 42%; most were related to underlying disease. The
      pharmacokinetic profile of CHO-derived siltuximab appears similar to the previous
      cell line. No objective responses occurred; 5 of 84 patients had stable disease
      >6 weeks. Hemoglobin increased >=1.5 g/dL in 33 of 47 patients. At 11 and 15
      mg/kg, completely sustained C-reactive protein suppression was observed.
      CONCLUSIONS: Siltuximab monotherapy appears to be well tolerated but without
      clinical activity in solid tumors, including ovarian and KRAS-mutant cancers. The
      recommended phase II doses were 11 and 15 mg/kg every 3 weeks.

PMID- 24563480
TI  - First-in-human phase I study of Lurbinectedin (PM01183) in patients with advanced
      solid tumors.
AB  - PURPOSE: Lurbinectedin (PM01183) binds covalently to DNA and has broad activity
      against tumor cell lines. This first-in-human phase I study evaluated dose
      limiting toxicities (DLT) and defined a phase II recommended dose for PM01183 as
      a 1-hour intravenous infusion every three weeks (q3wk). EXPERIMENTAL DESIGN:
      Thirty-one patients with advanced solid tumors received escalating doses of
      PM01183 following an accelerated titration design. RESULTS: PM01183 was safely
      escalated over 200-fold, from 0.02 to 5.0 mg/m(2). Dose doubling was utilized,
      requiring 15 patients and nine dose levels to identify DLT. The recommended dose
      was 4.0 mg/m(2), with one of 15 patients having DLT (grade 4 thrombocytopenia).
      Clearance was independent of body surface area; thus, a flat dose of 7.0 mg was
      used during expansion. Myelosuppression, mostly grade 4 neutropenia, occurred in
      40% of patients but was transient and manageable, and none was febrile. All other
      toxicity was mild and fatigue, nausea and vomiting were the most common at the
      recommended dose. Pharmacokinetic parameters showed high interindividual
      variation, though linearity was observed. At or above the recommended dose, the
      myelosuppressive effect was significantly associated with the area under the
      concentration-time curve from time zero to infinity (white blood cells, P =
      0.0007; absolute neutrophil count, P = 0.016). A partial response was observed in
      one patient with pancreatic adenocarcinoma at the recommended dose. CONCLUSION: A
      flat dose of 7.0 mg is the recommended dose for PM01183 as a 1-hour infusion
      q3wk. This dose is tolerated and active. Severe neutropenia occurred at this
      dose, although it was transient and with no clinical consequences in this study.

PMID- 24563481
TI  - Direct regulation of osteocytic connexin 43 hemichannels through AKT kinase
      activated by mechanical stimulation.
AB  - Connexin (Cx) 43 hemichannels in osteocytes are thought to play a critical role
      in releasing bone modulators in response to mechanical loading, a process
      important for bone formation and remodeling. However, the underlying mechanism
      that regulates the opening of mechanosensitive hemichannels is largely unknown.
      We have recently shown that Cx43 and integrin alpha5 interact directly with each
      other, and activation of PI3K appears to be required for Cx43 hemichannel opening
      by mechanical stimulation. Here, we show that mechanical loading through fluid
      flow shear stress (FFSS) increased the level of active AKT, a downstream effector
      of PI3K, which is correlated with the opening of hemichannels. Both Cx43 and
      integrin alpha5 are directly phosphorylated by AKT. Inhibition of AKT activation
      significantly reduced FFSS-induced opening of hemichannels and disrupted the
      interaction between Cx43 and integrin alpha5. Moreover, AKT phosphorylation on
      Cx43 and integrin alpha5 enhanced their interaction. In contrast to the C
      terminus of wild-type Cx43, overexpression of the C-terminal mutant containing
      S373A, a consensus site previously shown to be phosphorylated by AKT, failed to
      bind with alpha5 and hence could not inhibit hemichannel opening. Together, our
      results suggest that AKT activated by FFSS directly phosphorylates Cx43 and
      integrin alpha5, and Ser-373 of Cx43 plays a predominant role in mediating the
      interaction between these two proteins and Cx43 hemichannel opening, a crucial
      step to mediate the anabolic function of mechanical loading in the bone. 

PMID- 24563482
TI  - Myocilin regulates cell proliferation and survival.
AB  - Myocilin, a causative gene for open angle glaucoma, encodes a secreted
      glycoprotein with poorly understood functions. To gain insight into its
      functions, we produced a stably transfected HEK293 cell line expressing myocilin
      under an inducible promoter and compared gene expression profiles between
      myocilin-expressing and vector control cell lines by a microarray analysis. A
      significant fraction of differentially expressed genes in myocilin-expressing
      cells was associated with cell growth and cell death, suggesting that myocilin
      may have a role in the regulation of cell growth and survival. Increased
      proliferation of myocilin-expressing cells was demonstrated by the WST-1
      proliferation assay, direct cell counting, and immunostaining with antibodies
      against Ki-67, a cellular proliferation marker. Myocilin-containing conditioned
      medium also increased proliferation of unmodified HEK293 cells. Myocilin
      expressing cells were more resistant to serum starvation-induced apoptosis than
      control cells. TUNEL-positive apoptotic cells were dramatically decreased, and
      two apoptotic marker proteins, cleaved caspase 7 and cleaved poly(ADP-ribose)
      polymerase, were significantly reduced in myocilin-expressing cells as compared
      with control cells under apoptotic conditions. In addition, myocilin-deficient
      mesenchymal stem cells exhibited reduced proliferation and enhanced
      susceptibility to serum starvation-induced apoptosis as compared with wild-type
      mesenchymal stem cells. Phosphorylation of ERK1/2 and its upstream kinases, c-Raf
      and MEK, was increased in myocilin-expressing cells compared with control cells.
      Elevated phosphorylation of ERK1/2 was also observed in the trabecular meshwork
      of transgenic mice expressing 6-fold higher levels of myocilin when compared with
      their wild-type littermates. These results suggest that myocilin promotes cell
      proliferation and resistance to apoptosis via the ERK1/2 MAPK signaling pathway. 

PMID- 24563483
TI  - Ovarian cancer cell heparan sulfate 6-O-sulfotransferases regulate an angiogenic
      program induced by heparin-binding epidermal growth factor (EGF)-like growth
      factor/EGF receptor signaling.
AB  - Heparan sulfate (HS) is a component of cell surface and extracellular matrix
      proteoglycans that regulates numerous signaling pathways by binding and
      activating multiple growth factors and chemokines. The amount and pattern of HS
      sulfation are key determinants for the assembly of the trimolecular, HS-growth
      factor-receptor, signaling complex. Here we demonstrate that HS 6-O
      sulfotransferases 1 and 2 (HS6ST-1 and HS6ST-2), which perform sulfation at 6-O
      position in glucosamine in HS, impact ovarian cancer angiogenesis through the HS
      dependent HB-EGF/EGFR axis that subsequently modulates the expression of multiple
      angiogenic cytokines. Down-regulation of HS6ST-1 or HS6ST-2 in human ovarian
      cancer cell lines results in 30-50% reduction in glucosamine 6-O-sulfate levels
      in HS, impairing HB-EGF-dependent EGFR signaling and diminishing FGF2, IL-6, and
      IL-8 mRNA and protein levels in cancer cells. These cancer cell-related changes
      reduce endothelial cell signaling and tubule formation in vitro. In vivo, the
      development of subcutaneous tumor nodules with reduced 6-O-sulfation is
      significantly delayed at the initial stages of tumor establishment with further
      reduction in angiogenesis occurring throughout tumor growth. Our results show
      that in addition to the critical role that 6-O-sulfate moieties play in
      angiogenic cytokine activation, HS 6-O-sulfation level, determined by the
      expression of HS6ST isoforms in ovarian cancer cells, is a major regulator of
      angiogenic program in ovarian cancer cells impacting HB-EGF signaling and
      subsequent expression of angiogenic cytokines by cancer cells. 

PMID- 24563484
TI  - A mouse model for dominant collagen VI disorders: heterozygous deletion of Col6a3
      Exon 16.
AB  - Dominant and recessive mutations in collagen VI genes, COL6A1, COL6A2, and
      COL6A3, cause a continuous spectrum of disorders characterized by muscle weakness
      and connective tissue abnormalities ranging from the severe Ullrich congenital
      muscular dystrophy to the mild Bethlem myopathy. Herein, we report the
      development of a mouse model for dominant collagen VI disorders by deleting exon
      16 in the Col6a3 gene. The resulting heterozygous mouse, Col6a3(+/d16), produced
      comparable amounts of normal Col6a3 mRNA and a mutant transcript with an in-frame
      deletion of 54 bp of triple-helical coding sequences, thus mimicking the most
      common molecular defect found in dominant Ullrich congenital muscular dystrophy
      patients. Biosynthetic studies of mutant fibroblasts indicated that the mutant
      alpha3(VI) collagen protein was produced and exerted a dominant-negative effect
      on collagen VI microfibrillar assembly. The distribution of the alpha3(VI)-like
      chains of collagen VI was not altered in mutant mice during development. The
      Col6a3(+/d16) mice developed histopathologic signs of myopathy and showed
      ultrastructural alterations of mitochondria and sarcoplasmic reticulum in muscle
      and abnormal collagen fibrils in tendons. The Col6a3(+/d16) mice displayed
      compromised muscle contractile functions and thereby provide an essential
      preclinical platform for developing treatment strategies for dominant collagen VI
      disorders. 

PMID- 24563485
TI  - Fibroblast growth factor-based signaling through synthetic heparan sulfate blocks
      copolymers studied using high cell density three-dimensional cell printing.
AB  - Four well-defined heparan sulfate (HS) block copolymers containing S-domains
      (high sulfo group content) placed adjacent to N-domains (low sulfo group content)
      were chemoenzymatically synthesized and characterized. The domain lengths in
      these HS block co-polymers were ~40 saccharide units. Microtiter 96-well and
      three-dimensional cell-based microarray assays utilizing murine immortalized bone
      marrow (BaF3) cells were developed to evaluate the activity of these HS block co
      polymers. Each recombinant BaF3 cell line expresses only a single type of
      fibroblast growth factor receptor (FGFR) but produces neither HS nor fibroblast
      growth factors (FGFs). In the presence of different FGFs, BaF3 cell proliferation
      showed clear differences for the four HS block co-polymers examined. These data
      were used to examine the two proposed signaling models, the symmetric FGF2-HS2
      FGFR2 ternary complex model and the asymmetric FGF2-HS1-FGFR2 ternary complex
      model. In the symmetric FGF2-HS2-FGFR2 model, two acidic HS chains bind in a
      basic canyon located on the top face of the FGF2-FGFR2 protein complex. In this
      model the S-domains at the non-reducing ends of the two HS proteoglycan chains
      are proposed to interact with the FGF2-FGFR2 protein complex. In contrast, in the
      asymmetric FGF2-HS1-FGFR2 model, a single HS chain interacts with the FGF2-FGFR2
      protein complex through a single S-domain that can be located at any position
      within an HS chain. Our data comparing a series of synthetically prepared HS
      block copolymers support a preference for the symmetric FGF2-HS2-FGFR2 ternary
      complex model.

PMID- 24563487
TI  - Meta-analysis of bonding effectiveness to zirconia ceramics.
AB  - Dental zirconia can no longer be considered un-bondable to tooth tissue. In
      literature, an increasing number of papers indeed report on the bonding
      effectiveness of different luting techniques to zirconia. We aimed to disclose
      general trends in bonding to zirconia by systematically collecting zirconia bond
      strength data. A search in PubMed and EMBASE revealed 1,371 bond-strength tests
      reported on in 144 papers. A macro-shear bond-strength protocol was most
      frequently used; it revealed significantly lower bond strengths and was less
      discriminative than the other test methods. Regarding luting technique, the
      combination of mechanical and chemical pre-treatment appeared particularly
      crucial to obtain durable bonding to zirconia ceramics. The cement choice was not
      revealed as a determining factor after aging conditions, as long as composite
      cement was used. Regarding test protocol, a tensile test appeared more
      discriminative, particularly when combined with 'water storage' aging. 

PMID- 24563486
TI  - Strong association of variants around FOXE1 and orofacial clefting.
AB  - Nonsyndromic orofacial clefting (nsOFC) is a common, complex congenital disorder.
      The most frequent forms are nonsyndromic cleft lip with or without cleft palate
      (nsCL/P) and nonsyndromic cleft palate only (nsCPO). Although they are generally
      considered distinct entities, a recent study has implicated a region around the
      FOXE1 gene in both nsCL/P and nsCPO. To investigate this hypothesis, we analyzed
      the 2 most strongly associated markers (rs3758249 and rs4460498) in 2 independent
      samples of differing ethnicities: Central European (949 nsCL/P cases, 155 nsCPO
      cases, 1163 controls) and Mayan Mesoamerican (156 nsCL/P cases, 10 nsCPO cases,
      338 controls). While highly significant associations for both single-nucleotide
      polymorphisms were obtained in nsCL/P (rs4460498: p Europe = 6.50 * 10(-06), p
      Mayan = .0151; rs3758249: p Europe = 2.41 * 10(-05), p Mayan = .0299), no
      association was found in nsCPO (p > .05). Genotyping of rs4460498 in 472
      independent European trios revealed significant associations for nsCL/P (p =
      .016) and nsCPO (p = .043). A meta-analysis of all data revealed a genomewide
      significant result for nsCL/P (p = 1.31 * 10(-08)), which became more significant
      when nsCPO cases were added (p nsOFC = 1.56 * 10(-09)). These results strongly
      support the FOXE1 locus as a risk factor for nsOFC. With the data of the initial
      study, there is now considerable evidence that this locus is the first conclusive
      risk factor shared between nsCL/P and nsCPO. 

PMID- 24563489
TI  - Is it time to do away with the 99th percentile for cardiac troponin in the
      diagnosis of acute coronary syndrome and the assessment of cardiac risk?

PMID- 24563490
TI  - Profiling plasma microRNA in nasopharyngeal carcinoma with deep sequencing.
AB  - BACKGROUND: The goal of this study was to establish a plasma microRNA profile by
      use of next-generation sequencing that could aid in assessment of patient
      prognosis in nasopharyngeal carcinoma (NPC). METHODS: Two panels of NPC patients
      and healthy controls (HCs) were recruited for this study. We used deep sequencing
      to screen plasma microRNAs. Differentially expressed microRNAs were verified by
      quantitative real-time PCR (qPCR). Kaplan-Meier survival analysis with the log
      rank test was used to compare overall survival (OS) and progression-free survival
      (PFS) between groups. RESULTS: Twenty-three plasma miRNAs with differential
      expression levels were selected for qPCR analysis on an independent set including
      100 NPC patients and 55 HCs. NPC patients with low concentrations of miR-483-5p
      and miR-103 had better prognosis for 5-year OS than those with high
      concentrations (87.5% vs 55.8%, P < 0.001; 80.9% vs 62.3%, P = 0.031). Those with
      low concentrations of miR-29a and let-7c had poorer prognosis (54.8% vs 82.8%, P
      = 0.002; 56.3% vs 84.6%, P = 0.001). A 3-signature miRNA integrated with clinical
      stage was further identified in an independent set. We calculated a prognostic
      index score and classified patients into low-, medium-, and high-risk groups.
      Five-year OS among the 3 groups was significantly different (90.9%, 66.7%, and
      23.8%; P < 0.001). By multivariate analysis, a high-risk score was the most
      significantly unfavorable prognostic factor independent of other clinical
      variables (P < 0.001, hazard ratio = 15.1, 95% CI = 5.2-43.9). CONCLUSIONS:
      Differentially expressed plasma miRNAs as identified by next-generation
      sequencing can be helpful for predicting survival in NPC patients.

PMID- 24563491
TI  - Phase I and II cannabinoid disposition in blood and plasma of occasional and
      frequent smokers following controlled smoked cannabis.
AB  - BACKGROUND: Delta(9)-Tetrahydrocannabinol (THC), 11-hydroxy-THC (11-OH-THC), and
      11-nor-9-carboxy-THC (THCCOOH) have been reported in blood from frequent cannabis
      smokers for an extended time during abstinence. We compared THC, 11-OH-THC,
      THCCOOH, cannabidiol, cannabinol, THC-glucuronide, and 11-nor-9-carboxy-THC
      glucuronide (THCCOO-glucuronide) blood and plasma disposition in frequent and
      occasional cannabis smokers. METHODS: Frequent and occasional smokers resided on
      a closed research unit and smoked one 6.8% THC cannabis cigarette ad libitum.
      Blood and plasma cannabinoids were quantified on admission (approximately 19 h
      before), 1 h before, and up to 15 times (0.5-30 h) after smoking. RESULTS:
      Cannabinoid blood and plasma concentrations were significantly higher in frequent
      smokers compared with occasional smokers at most time points for THC and 11-OH
      THC and at all time points for THCCOOH and THCCOO-glucuronide. Cannabidiol,
      cannabinol, and THC-glucuronide were not significantly different at any time
      point. Overall blood and plasma cannabinoid concentrations were significantly
      higher in frequent smokers for THC, 11-OH-THC, THCCOOH, and THCCOO-glucuronide,
      with and without accounting for baseline concentrations. For blood THC >5 MUg/L,
      median (range) time of last detection was 3.5 h (1.1->30 h) in frequent smokers
      and 1.0 h (0-2.1 h) in 11 occasional smokers; 2 individuals had no samples with
      THC >5 MUg/L. CONCLUSIONS: Cannabis smoking history plays a major role in
      cannabinoid detection. These differences may impact clinical and impaired driving
      drug detection. The presence of cannabidiol, cannabinol, or THC-glucuronide
      indicates recent use, but their absence does not exclude it.

PMID- 24563492
TI  - Feline diabetes mellitus: clinical use of long-acting glargine and detemir.
AB  - PRACTICAL RELEVANCE: Diabetes mellitus is a common endocrine disorder in feline
      practice, affecting approximately 1 in 200 cats. The majority of diabetic cats
      have type 2 diabetes mellitus, which results from a combination of peripheral
      insulin resistance and a progressive reduction in insulin production. CLINICAL
      CHALLENGES: While usually easy to diagnose, management of diabetes mellitus
      presents a number of challenges for practitioners and clients alike.
      Practitioners must decide on diet, insulin type and dose, monitoring method and
      intensity, and concomitant therapy, which will vary based on individual patient
      and client needs, and geographic location. Practitioners may also encounter
      patients with diabetic ketoacidosis or other diabetic complications, and patients
      with multiple concurrent diseases. Clients may be challenged by the substantial
      time and financial commitment involved in owning a diabetic cat. AUDIENCE:
      Understanding the pathophysiology, optimal treatment protocols and current goals
      of diabetes management will benefit practitioners managing diabetic cats. This
      article reviews the most current management plans for feline diabetics. It places
      particular emphasis on best practice for achieving diabetic remission, which is
      an attainable goal in the majority of newly diagnosed diabetic cats. EVIDENCE
      BASE: The information in this article is drawn from the recent human and
      veterinary literature, including prospective and retrospective studies. The body
      of prospective clinical data on the use of newer, long-acting insulins (glargine
      and especially detemir) in cats is limited, but growing.

PMID- 24563493
TI  - Investigation of parenchymal abdominal organ disease in cats: aiming for the
      ideal biopsy.
AB  - PRACTICAL RELEVANCE: Definitive diagnosis of disease involving the parenchymal
      abdominal viscera often requires a representative specimen of affected tissue.
      Methods used to obtain tissue samples range from those that are minimally
      invasive, such as fine-needle aspiration (FNA), to more invasive techniques such
      as surgical biopsy. CLINICAL CHALLENGES: FNA and cytological examination can be a
      useful diagnostic tool and is commonly used for hepatic, splenic and lymph node
      specimens. FNA is an easy and cheap procedure that is best suited to diffuse
      disease and can be performed at low risk to the patient. However, its accuracy
      and agreement with the histopathological findings vary depending on the
      underlying disease and it often fails to provide information on parenchymal
      architecture. Importantly, FNA for cytological examination of the liver has
      serious limitations when used to identify the primary disease process due to the
      small sample size obtained. AUDIENCE: This review is aimed at clinicians
      undertaking more detailed and specialist investigation of diseases of feline
      parenchymal abdominal organs and provides practical guidance on the different
      methods used to obtain hepatic, renal, pancreatic and splenic specimens in cats.
      EVIDENCE BASE: The information presented is based on peer-reviewed publications
      and the clinical experience of the author.

PMID- 24563494
TI  - Feline gastrointestinal surgery: principles and essential techniques.
AB  - PRACTICAL RELEVANCE: Gastrointestinal (GI) surgical procedures are performed
      commonly in cats in general practice for both diagnostic and treatment purposes.
      It is essential that the surgeon understands and adheres to the principles of GI
      surgery in order that postoperative morbidity and mortality are kept to a
      minimum. AUDIENCE: This review is aimed at feline and general practitioners
      wanting to update their core skills in GI surgery. It discusses anatomical
      considerations and surgical principles, and aims to familiarise the surgeon with
      techniques (some well established, others newer) that will help to promote
      surgical success. EQUIPMENT: Standard general surgical equipment is required,
      together with the facilities to provide adequate pre-, intra- and postoperative
      patient care. EVIDENCE BASE: The author draws on clinical experience and evidence
      from the literature, where appropriate, in reviewing the guidance and techniques
      under discussion.

PMID- 24563495
TI  - Primary hypodipsia in a cat with severe hypernatremia.
AB  - CLINICAL SUMMARY: A 4.5-year-old male castrated domestic shorthair cat presented
      with a 2-month history of muscle tremors progressing to weakness, pelvic limb
      ataxia, mild facial twitching, poor appetite and polyuria. Primary hypodipsia and
      resultant hypernatremia was diagnosed. Intensive fluid therapy and monitoring
      were initially required for stabilization, and the cat's condition was
      successfully managed long-term using canned food supplemented with additional
      water. PRACTICAL RELEVANCE: Primary hypodipsia is rare in clinical practice, but
      experience with this case suggests that associated hypernatremia can be
      successfully managed using a water-enriched diet to provide maintenance
      hydration.

PMID- 24563496
TI  - Hypervitaminosis A-induced hepatic fibrosis in a cat.
AB  - RATIONALE: The excessive intake of vitamin A in the form of vitamin concentrate,
      supplement or vitamin-rich liver can result in hypervitaminosis A in man and
      animals. Although osteopathologies resulting from chronic vitamin A intoxication
      in cats are well characterized, no information is available concerning feline
      hypervitaminosis A-induced liver disease. CLINICAL SUMMARY: We report the first
      case of hepatic stellate cell lipidosis and hepatic fibrosis in a domestic cat
      that had been fed a diet based on raw beef liver. Radiographic examination
      revealed exostoses and ankylosis between vertebrae C1 and T7, compatible with
      deforming cervical spondylosis. Necropsy showed a slightly enlarged and light
      yellow to bronze liver. Microscopic and ultrastructural analyses of liver tissues
      revealed diffuse and severe liver fibrosis associated with hepatic stellate cell
      hyperplasia and hypertrophy. These cells showed immunopositive staining for alpha
      smooth muscle actin and desmin markers. The necropsy findings of chronic liver
      disease coupled with osteopathology supported the diagnosis of hypervitaminosis
      A. PRACTICAL RELEVANCE: As in human hepatology, if there is dietary evidence to
      support increased intake of vitamin A, then hypervitaminosis A should be
      considered in the differential diagnosis of chronic liver disease in cats.

PMID- 24563499
TI  - What patients want from the treatment of Dupuytren's disease--is the Unite
      Rhumatologique des Affections de la Main (URAM) scale relevant?
AB  - Patients awaiting surgery for Dupuytren's contractures listed the problems from
      their Dupuytren's disease that had led them to request surgery and their relative
      priorities of the results of surgery. The listed problems were compared with the
      nine items comprising the Unite Rhumatologique des Affections de la Main (URAM)
      Dupuytren's disease-specific outcome measure. One hundred and ten patients
      reported 278 problems. Ninety-four different combinations of problems were
      provided by patients, and over half (55%) of the problems were not captured by
      items in the URAM scale. The long-term outcome from surgery was relatively more
      important to patients than speed of recovery. The URAM tool may not be relevant
      to patients in the UK, and further assessment of its face validity is required
      before it is used.

PMID- 24563498
TI  - Open surgery versus nonoperative treatments for paediatric trigger thumb: a
      systematic review.
AB  - The purpose of this systematic review was to determine the outcome of
      interphalangeal (IP) joint motion in children undergoing open surgical release,
      splinting, and passive exercising therapy for the treatment of paediatric trigger
      thumb. We conducted an online literature search of seven major databases. Only
      studies with a mean follow-up of at least 12 months were considered for
      inclusion. Seventeen retrospective studies and one prospective study met all the
      inclusion criteria. They reported on the results of surgery (634 children, 759
      thumbs), splinting (115 children, 138 thumbs), and passive exercising (89
      children, 108 thumbs). The mean follow-up periods were 59 (surgery), 23
      (splinting), and 76 months (exercising), respectively. Full IP joint motion
      without residual triggering was achieved in 95% of all children undergoing
      surgery, in 67% of children treated with continuous splinting, and 55% after
      passive exercising. Based on the low level of evidence available, it seems that
      open surgery resulted in more reliable and rapid outcomes compared with
      nonoperative treatment. 

PMID- 24563500
TI  - The effect of testosterone on cardiovascular disease: a critical review of the
      literature.
AB  - Cardiovascular disease is the leading cause of death in the United States.
      Testosterone is the principal male sex hormone and plays an important role in
      men's health and well-being. Historically, testosterone was believed to adversely
      affect cardiovascular function. However, contemporary literature has refuted this
      traditional thinking; testosterone has been suggested to have a protective effect
      on cardiovascular function through its effects on the vascular system. Data from
      modern research indicate that hypogonadism is closely related to the development
      of various cardiovascular risk factors, including hyperlipidemia and insulin
      resistance. Several studies have demonstrated beneficial effects of testosterone
      supplementation therapy on reversing symptoms of hypogonadism and improving
      cardiovascular disease risk profiles. In this review, we perform a critical
      analysis on the association between testosterone and cardiovascular disease. 

PMID- 24563501
TI  - Costs of illness and quality of life in patients with systemic lupus
      erythematosus in South Korea.
AB  - OBJECTIVE: To assess the costs of illness, health-related quality of life (HRQOL)
      and their associated factors in patients with systemic lupus erythematosus (SLE)
      in South Korea. METHOD: Two hundred and one patients with SLE were enrolled at
      the Rheumatology clinic of Seoul National University Hospital. Direct, indirect
      and total costs and HRQOL were measured using hospital electronic data and face
      to-face interview. Socio-demographic and clinical factors associated with cost of
      illness and HRQOL were analyzed using multiple regression and multivariate
      logistic regression. RESULTS: The average total cost of illness was estimated to
      be KRW 9.82 million (US $ 8993) per year, of which 41.6% was accounted for by
      direct costs and 58.4% by indirect costs. In multivariate regression, patients
      with renal involvement and those with depression incurred an average increment in
      annual total costs of 37.6% (p = 0.050) and 49.1% (p = 0.024), respectively, and
      an average increment in annual direct costs of 26.4% (p = 0.050) and 43.3% (p =
      0.002), respectively, compared with patients without renal involvement and
      depression, respectively. In addition, disease damage was positively associated
      with an average increment in annual total and direct costs (55.3%, p = 0.006;
      33.3%, p = 0.013, respectively), and the occurrence of indirect costs (OR 2.21,
      1.09-4.88). There was no significant difference in HRQOL between patients with
      and without renal involvement (0.655 vs. 0.693, p = 0.203) CONCLUSION: Renal
      involvement, depression, and disease damage were major factors associated with
      higher total and medical costs for patients with SLE in South Korea. Effective
      treatment of renal disorders and depression may reduce the high economic burden
      of SLE.

PMID- 24563503
TI  - Blown away: the unexpected role of lymphotoxin in lymphoid organ development.

PMID- 24563502
TI  - Standardizing scavenger receptor nomenclature.
AB  - Scavenger receptors constitute a large family of proteins that are structurally
      diverse and participate in a wide range of biological functions. These receptors
      are expressed predominantly by myeloid cells and recognize a variety of ligands,
      including endogenous and modified host-derived molecules and microbial pathogens.
      There are currently eight classes of scavenger receptors, many of which have
      multiple names, leading to inconsistencies and confusion in the literature. To
      address this problem, a workshop was organized by the U.S. National Institute of
      Allergy and Infectious Diseases, National Institutes of Health to help develop a
      clear definition of scavenger receptors and a standardized nomenclature based on
      that definition. Fifteen experts in the scavenger receptor field attended the
      workshop and, after extensive discussion, reached a consensus regarding the
      definition of scavenger receptors and a proposed scavenger receptor nomenclature.
      Scavenger receptors were defined as cell surface receptors that typically bind
      multiple ligands and promote the removal of non-self or altered-self targets.
      They often function by mechanisms that include endocytosis, phagocytosis,
      adhesion, and signaling that ultimately lead to the elimination of degraded or
      harmful substances. Based on this definition, nomenclature and classification of
      these receptors into 10 classes were proposed. The discussion and nomenclature
      recommendations described in this report only refer to mammalian scavenger
      receptors. The purpose of this article is to describe the proposed mammalian
      nomenclature and classification developed at the workshop and to solicit
      additional feedback from the broader research community. 

PMID- 24563504
TI  - Pillars article: Abnormal development of peripheral lymphoid organs in mice
      deficient in lymphotoxin. Science. 1994. 264: 703-707.

PMID- 24563505
TI  - Pillars article: A lymphotoxin-B-specific receptor. Science. 1994. 264: 707-710.

PMID- 24563510
TI  - Measurement of lysophospholipid acyltransferase activities using substrate
      competition.
AB  - Lysophospholipid acyltransferases (LPATs) incorporate fatty acyl chains into
      phospholipids via a CoA-dependent mechanism and are important in remodeling
      phospholipids to generate the molecular species of phospholipids found in cells.
      These enzymes use one lysophospholipid and one acyl-CoA ester as substrates.
      Traditional enzyme activity assays engage a single substrate pair, whereas in
      vivo multiple molecular species exist. We describe here an alternative
      biochemical assay that provides a mixture of substrates presented to the
      microsomal extracts. Microsomal preparations from RAW 264.7 cells were used to
      compare traditional LPAT assays with data obtained using a dual substrate choice
      assay using six different lysophospholipids and eight different acyl-CoA esters.
      The complex mixture of newly synthesized phospholipid products was analyzed using
      LC-MS/MS. Both types of assays provided similar results, but the dual choice
      assay provided information about multiple fatty acyl chain incorporation into
      various phospholipid classes in a single reaction. Engineered suppression of
      LPCAT3 activity in RAW 264.7 cells was easily detected by the dual choice method.
      These findings demonstrate that this assay is both specific and sensitive and
      that it provides much richer biochemical detail than traditional assays. 

PMID- 24563512
TI  - The long and winding road.

PMID- 24563513
TI  - Doctor who?

PMID- 24563506
TI  - True grit: programmed necrosis in antiviral host defense, inflammation, and
      immunogenicity.
AB  - Programmed necrosis mediated by receptor interacting protein kinase (RIP)3 (also
      called RIPK3) has emerged as an alternate death pathway triggered by TNF family
      death receptors, pathogen sensors, IFNRs, Ag-specific TCR activation, and
      genotoxic stress. Necrosis leads to cell leakage and acts as a "trap door,"
      eliminating cells that cannot die by apoptosis because of the elaboration of
      pathogen-encoded caspase inhibitors. Necrotic signaling requires RIP3 binding to
      one of three partners-RIP1, DAI, or TRIF-via a common RIP homotypic interaction
      motif. Once activated, RIP3 kinase targets the pseudokinase mixed lineage kinase
      domain-like to drive cell lysis. Although necrotic and apoptotic death can
      enhance T cell cross-priming during infection, mice that lack these extrinsic
      programmed cell death pathways are able to produce Ag-specific T cells and
      control viral infection. The entwined relationship of apoptosis and necrosis
      evolved in response to pathogen-encoded suppressors to support host defense and
      contribute to inflammation. 

PMID- 24563511
TI  - Liver-specific transgenic expression of cholesteryl ester hydrolase reduces
      atherosclerosis in Ldlr-/- mice.
AB  - The liver plays a central role in the final elimination of cholesterol from the
      body either as bile acids or as free cholesterol (FC), and lipoprotein-derived
      cholesterol is the major source of total biliary cholesterol. HDL is the major
      lipoprotein responsible for removal and transport of cholesterol, mainly as
      cholesteryl esters (CEs), from the peripheral tissues to the liver. While HDL-FC
      is rapidly secreted into bile, the fate of HDL-CE remains unclear. We have
      earlier demonstrated the role of human CE hydrolase (CEH, CES1) in hepatic
      hydrolysis of HDL-CE and increasing bile acid synthesis, a process dependent on
      scavenger receptor BI expression. In the present study, we examined the
      hypothesis that by enhancing the elimination of HDL-CE into bile/feces, liver
      specific transgenic expression of CEH will be anti-atherogenic. Increased CEH
      expression in the liver significantly increased the flux of HDL-CE to bile acids.
      In the LDLR(-/-) background, this enhanced elimination of cholesterol led to
      attenuation of diet-induced atherosclerosis with a consistent increase in fecal
      sterol secretion primarily as bile acids. Taken together with the observed
      reduction in atherosclerosis by increasing macrophage CEH-mediated cholesterol
      efflux, these studies establish CEH as an important regulator in enhancing
      cholesterol elimination and also as an anti-atherogenic target. 

PMID- 24563509
TI  - Th17 cells and Tregs: unlikely allies.
AB  - Identification of CD4+Foxp3+ Tregs and Th17 modified the historical Th1-Th2
      paradigm. Currently, the Th17-Tregs dichotomy provides a dominant conceptual
      framework for the comprehension of immunity/inflammation and
      tolerance/immunosuppression in an increasing number of diseases. Targeting
      proinflammatory Th17 cells or immunosuppressive Tregs has been widely considered
      as a promising therapeutic strategy in the treatment of major human diseases,
      including autoimmunity and cancer. The efficacy and safety of such therapy rely
      on a thorough understanding of immunobiology and interaction of these two subsets
      of Th cells. In this article, we review recent progress concerning complicated
      interplay of Th17 cells and Tregs There is compelling evidence that Tregs
      potently inhibit Th1 and Th2 responses; however, the inhibitory effect of Tregs
      on Th17 responses is a controversial subject. There is increasing evidence
      showing that Tregs actually promote the differentiation of Th17 cells in vitro
      and in vivo and consequently, enhanced the functional consequences of Th17 cells,
      including the protective effect in host defense, as well as detrimental effect in
      inflammation and in the support of tumor growth. On the other hand, Th17 cells
      were also the most potent Th subset in the stimulation and support of expansion
      and phenotypic stability of Tregs in vivo. These results indicate that these two
      subsets of Th cells reciprocally stimulate each other. This bidirectional
      crosstalk is largely dependent on the TNF-TNFR2 pathway. These mutual stimulatory
      effects should be considered in devising future Th17 cell- and Treg-targeting
      therapy.

PMID- 24563514
TI  - RNase E forms a complex with polynucleotide phosphorylase in cyanobacteria via a
      cyanobacterial-specific nonapeptide in the noncatalytic region.
AB  - RNase E, a central component involved in bacterial RNA metabolism, usually has a
      highly conserved N-terminal catalytic domain but an extremely divergent C
      terminal domain. While the C-terminal domain of RNase E in Escherichia coli
      recruits other components to form an RNA degradation complex, it is unknown if a
      similar function can be found for RNase E in other organisms due to the divergent
      feature of this domain. Here, we provide evidence showing that RNase E forms a
      complex with another essential ribonuclease-the polynucleotide phosphorylase
      (PNPase)-in cyanobacteria, a group of ecologically important and phylogenetically
      ancient organisms. Sequence alignment for all cyanobacterial RNase E proteins
      revealed several conserved and variable subregions in their noncatalytic domains.
      One such subregion, an extremely conserved nonapeptide (RRRRRRSSA) located near
      the very end of RNase E, serves as the PNPase recognition site in both the
      filamentous cyanobacterium Anabaena PCC7120 and the unicellular cyanobacterium
      Synechocystis PCC6803. These results indicate that RNase E and PNPase form a
      ribonuclease complex via a common mechanism in cyanobacteria. The PNPase
      recognition motif in cyanobacterial RNase E is distinct from those previously
      identified in Proteobacteria, implying a mechanism of coevolution for PNPase and
      RNase E in different organisms. 

PMID- 24563515
TI  - Transcriptomic architecture of the adjacent airway field cancerization in non
      small cell lung cancer.
AB  - BACKGROUND: Earlier work identified specific tumor-promoting abnormalities that
      are shared between lung cancers and adjacent normal bronchial epithelia. We
      sought to characterize the yet unknown global molecular and adjacent airway field
      cancerization (FC) in early-stage non-small cell lung cancer (NSCLC). METHODS:
      Whole-transcriptome expression profiling of resected early-stage (I-IIIA) NSCLC
      specimens (n = 20) with matched tumors, multiple cytologically controlled normal
      airways with varying distances from tumors, and uninvolved normal lung tissues (n
      = 194 samples) was performed using the Affymetrix Human Gene 1.0 ST platform.
      Mixed-effects models were used to identify differentially expressed genes among
      groups. Ordinal regression analysis was performed to characterize site-dependent
      airway expression profiles. All statistical tests were two-sided, except where
      noted. RESULTS: We identified differentially expressed gene features (n = 1661)
      between NSCLCs and airways compared with normal lung tissues, a subset of which
      (n = 299), after gene set enrichment analysis, statistically significantly (P <
      .001) distinguished large airways in lung cancer patients from airways in cancer
      free smokers. In addition, we identified genes (n = 422) statistically
      significantly and progressively differentially expressed in airways by distance
      from tumors that were found to be congruently modulated between NSCLCs and normal
      lung tissues. Furthermore, LAPTM4B, with statistically significantly increased
      expression (P < .05) in airways with shorter distance from tumors, was
      upregulated in human immortalized cells compared with normal bronchial epithelial
      cells (P < .001) and promoted anchorage-dependent and -independent lung cancer
      cell growth. CONCLUSIONS: The adjacent airway FC comprises both site-independent
      profiles as well as gradient and localized airway expression patterns. Profiling
      of the airway FC may provide new insights into NSCLC oncogenesis and molecular
      tools for detection of the disease.

PMID- 24563516
TI  - Pancreatic adenocarcinoma: treating a systemic disease with systemic therapy.
AB  - Pancreatic adenocarcinoma, even when resectable, remains highly lethal. Although
      surgical outcomes have improved considerably, median overall survival after
      surgery and adjuvant therapy such as single-agent gemcitabine remains less than 2
      years. We discuss preclinical and clinical data supporting the contention that
      even early-stage pancreatic cancer is a systemic disease. Autopsy series reveal
      that 70% to 85% of patients die of systemic recurrence, rather than local
      disease, after pancreatic cancer resection. Preclinical studies using genomics
      and mouse models reveal evidence of metastatic spread even before histopathologic
      evidence of a pancreatic tumor. Analogous to breast cancer, we propose that the
      Halstedian approach of treating pancreatic cancer as a local, surgical problem
      should be replaced by Fisher's alternative hypothesis of cancer as a systemic
      disease. Newer multiagent chemotherapy regimens have shown meaningful response
      rates and improvement in overall survival in the metastatic setting and, for the
      first time, offer investigators an opportunity to use effective systemic therapy.
      We emphasize that a surgery-first approach is not resonant with our current
      understanding of pancreatic adenocarcinoma biology and that an upfront systemic
      approach for even resectable pancreatic cancer warrants testing in clinical
      trials. 

PMID- 24563517
TI  - Selenoprotein gene variants, toenail selenium levels, and risk for advanced
      prostate cancer.
AB  - Lower selenium levels have been associated with increased risk of prostate cancer
      (PCa), and genetic variation in the selenoprotein genes selenoprotein P (SEPP1)
      and glutathione peroxidase 1 (GPX1) is thought to modify this relationship. We
      investigated whether the association between toenail selenium levels and advanced
      PCa risk in the prospective Netherlands Cohort Study is modified by common
      genetic variation in SEPP1 and GPX1. Toenail clippings were used to determine
      selenium levels and to isolate DNA for genotyping. This case-cohort study, which
      included 817 case subjects with advanced PCa and 1048 subcohort members, was
      analyzed with Cox regression models. All statistical tests were two-sided. Three
      genetic variants were associated with advanced (stage III/IV or IV) PCa risk:
      SEPP1 rs7579 (lower risk; P trend = .01), GPX1 rs17650792 (higher risk; P trend =
      .03), and GPX1 rs1800668 (lower risk; P trend = .005). Toenail selenium levels
      were inversely associated with advanced PCa risk, independently of common genetic
      variation in SEPP1 and GPX1. 

PMID- 24563518
TI  - Effect of VIA screening by primary health workers: randomized controlled study in
      Mumbai, India.
AB  - BACKGROUND: Cervical cancer is the leading cause of cancer mortality among women
      in India. Because Pap smear screening is not feasible in India, we need to
      develop effective alternatives. METHODS: A cluster-randomized controlled study
      was initiated in 1998 in Mumbai, India, to investigate the efficacy of visual
      inspection with acetic acid (VIA) performed by primary health workers in reducing
      cervical cancer mortality. Four rounds of cancer education and VIA screening were
      conducted at 24-month intervals in the screening group, whereas cancer education
      was offered once at entry to the control group. The study was planned for 16
      years to include four screening rounds followed by four monitoring rounds. We
      present results after 12 years of follow-up. Poisson regression method was used
      to calculate the rate ratios (RRs); two-sided chi(2) was used to calculate the
      probability. RESULTS: We recruited 75360 women from 10 clusters in the screening
      group and 76178 women from 10 comparable clusters in the control group. In the
      screening group, we achieved 89% participation for screening and 79.4% compliance
      for diagnosis confirmation. The incidence of invasive cervical cancer was 26.74
      per 100000 (95% confidence interval [CI] = 23.41 to 30.74) in the screening group
      and 27.49 per 100000 (95% CI = 23.66 to 32.09) in the control group. Compliance
      to treatment for invasive cancer was 86.3% in the screening group and 72.3% in
      the control group. The screening group showed a statistically significant 31%
      reduction in cervical cancer mortality (RR = 0.69; 95% CI = 0.54 to 0.88; P =
      .003). CONCLUSIONS: VIA screening by primary health workers statistically
      significantly reduced cervical cancer mortality. Our study demonstrates the
      efficacy of an easily implementable strategy that could prevent 22000 cervical
      cancer deaths in India and 72600 deaths in resource-poor countries annually.

PMID- 24563520
TI  - Baseline selenium and prostate cancer risk: comments and open questions.

PMID- 24563519
TI  - Baseline selenium status and effects of selenium and vitamin e supplementation on
      prostate cancer risk.
AB  - BACKGROUND: The Selenium and Vitamin E Cancer Prevention Trial found no effect of
      selenium supplementation on prostate cancer (PCa) risk but a 17% increased risk
      from vitamin E supplementation. This case-cohort study investigates effects of
      selenium and vitamin E supplementation conditional upon baseline selenium status.
      METHODS: There were 1739 total and 489 high-grade (Gleason 7-10) PCa cases and
      3117 men in the randomly selected cohort. Proportional hazards models estimated
      hazard ratios (HRs) and 95% confidence intervals (CIs) for effects of
      supplementation within quintiles of baseline toenail selenium. Cox proportional
      hazards models were used to estimate hazard ratios, and all statistical tests are
      two-sided. RESULTS: Toenail selenium, in the absence of supplementation, was not
      associated with PCa risk. Selenium supplementation (combined selenium only and
      selenium + vitamin E arms) had no effect among men with low selenium status
      (<60th percentile of toenail selenium) but increased the risk of high-grade PCa
      among men with higher selenium status by 91% (P = .007). Vitamin E
      supplementation (alone) had no effect among men with high selenium status (>=40th
      percentile of toenail selenium) but increased the risks of total, low-grade, and
      high-grade PCa among men with lower selenium status (63%, P = .02; 46%, P = .09;
      111%, P = .008, respectively). CONCLUSIONS: Selenium supplementation did not
      benefit men with low selenium status but increased the risk of high-grade PCa
      among men with high selenium status. Vitamin E increased the risk of PCa among
      men with low selenium status. Men should avoid selenium or vitamin E
      supplementation at doses that exceed recommended dietary intakes.

PMID- 24563521
TI  - An MRI review of acquired corpus callosum lesions.
AB  - Lesions of the corpus callosum (CC) are seen in a multitude of disorders
      including vascular diseases, metabolic disorders, tumours, demyelinating
      diseases, trauma and infections. In some diseases, CC involvement is typical and
      sometimes isolated, while in other diseases CC lesions are seen only occasionally
      in the presence of other typical extra-callosal abnormalities. In this review, we
      will mainly discuss the MRI characteristics of acquired lesions involving the CC.
      Identification of the origin of the CC lesion depends on the exact localisation
      of the lesion(s) inside the CC, presence of other lesions seen outside the CC,
      signal changes on different MRI sequences, evolution over time of the
      radiological abnormalities, history and clinical state of the patient, and other
      radiological and non-radiological examinations. 

PMID- 24563522
TI  - Development of prediction models for radioactive caesium distribution within the
      80-km radius of the Fukushima Daiichi nuclear power plant.
AB  - Preliminary prediction models have been studied for the radioactive caesium
      distribution within the 80-km radius of the Fukushima Daiichi nuclear power
      plant. The models were represented by exponential functions using ecological half
      life of radioactive caesium in the environment. The ecological half-lives were
      derived from the changes in ambient dose equivalent rates through vehicle-borne
      surveys. It was found that the ecological half-lives of radioactive caesium were
      not constant within the 80-km radius of the Fukushima Daiichi nuclear power
      plant. The ecological half-life of radioactive caesium in forest areas was found
      to be much larger than that in urban and water areas. 

PMID- 24563523
TI  - Determination of 234U/238U, 235U/238U and 236U/238U isotope ratios in urine using
      sector field inductively coupled plasma mass spectrometry.
AB  - Quantification of the isotopic composition of uranium in urine at low levels of
      concentration is important for assessing both military and civilian populations'
      exposures to uranium. However, until now there has been no convenient, precise
      method established for rapid determination of multiple uranium isotope ratios.
      Here, the authors report a new method to measure (234)U/(238)U, (235)U/(238)U and
      (236)U/(238)U. It uses solid-phase chelation extraction (via TRU columns) of
      actinides from the urine matrix, followed by measurement using a magnetic sector
      field inductively coupled plasma mass spectrometer (SF-ICP-MS-Thermo Element XR)
      equipped with a high-efficiency nebulizer (Apex PFA microflow) and coupled with a
      membrane desolvating nebulizer system (Aridus IITM). This method provides rapid
      and reliable results and has been used successfully to analyse Certified
      Reference Materials. 

PMID- 24563524
TI  - Response of dosemeters in the radiation field generated by a TW-class laser
      system.
AB  - State-of-the-art laser systems are able to generate ionising radiation of
      significantly high energies by focusing ultra-short and intense pulses onto
      targets. Thus, measures ensuring the radiation protection of both working
      personnel and the general public are required. However, commercially available
      dosemeters are primarily designed for measurement in continuous fields.
      Therefore, it is important to explore their response to very short pulses. In
      this study, the responses of dosemeters in a radiation field generated by iodine
      high-power and Ti:Sapphire laser systems are examined in proton and electron
      acceleration experiments. Within these experiments, electron bunches of
      femtosecond pulse duration and 100-MeV energy and proton bunches with sub
      nanosecond pulse duration and energy of several megaelectronvolts were generated
      in single-shot regimes. Responses of typical detectors (TLD, films and electronic
      personal dosemeter) were analysed and compared. Further, a first attempt was
      carried out to characterise the radiation field generated by TW-class laser
      systems. 

PMID- 24563525
TI  - Does the use of additional X-ray beam filtration during cine acquisition reduce
      clinical image quality and effective dose in cardiac interventional imaging?
AB  - The impact of spectral filtration in digital ('cine') acquisition was
      investigated using a flat panel cardiac interventional X-ray imaging system. A
      0.1-mm copper (Cu) and 1.0-mm aluminium (Al) filter added to the standard
      acquisition mode created the filtered mode for comparison. Image sequences of 35
      patients were acquired, a double-blind subjective image quality assessment was
      completed and dose-area product (DAP) rates were calculated. Entrance surface
      dose (ESD) and effective dose (E) rates were determined for 20- and 30-cm
      phantoms. Phantom ESD fell by 28 and 41 % and E by 1 and 0.7 %, for the 20- and
      30-cm phantoms, respectively, when using the filtration. Patient DAP rates fell
      by 43 % with no statistically significant difference in clinical image quality.
      Adding 0.1-mm Cu and 1.0-mm Al filtration in acquisition substantially reduces
      patient ESD and DAP, with no significant change in E or clinical image quality. 

PMID- 24563527
TI  - The effects of surface gloss and roughness on color constancy for real 3-D
      objects.
AB  - Color constancy denotes the phenomenon that the appearance of an object remains
      fairly stable under changes in illumination and background color. Most of what we
      know about color constancy comes from experiments using flat, matte surfaces
      placed on a single plane under diffuse illumination simulated on a computer
      monitor. Here we investigate whether material properties (glossiness and
      roughness) have an effect on color constancy for real objects. Subjects matched
      the color and brightness of cylinders (painted red, green, or blue) illuminated
      by simulated daylight (D65) or by a reddish light with a Munsell color book
      illuminated by a tungsten lamp. The cylinders were either glossy or matte and
      either smooth or rough. The object was placed in front of a black background or a
      colored checkerboard. We found that color constancy was significantly higher for
      the glossy objects compared to the matte objects, and higher for the smooth
      objects compared to the rough objects. This was independent of the background. We
      conclude that material properties like glossiness and roughness can have
      significant effects on color constancy. 

PMID- 24563526
TI  - Interactions between concentric form-from-structure and face perception revealed
      by visual masking but not adaptation.
AB  - Findings from diverse subfields of vision research suggest a potential link
      between high-level aspects of face perception and concentric form-from-structure
      perception. To explore this relationship, typical adults performed two adaptation
      experiments and two masking experiments to test whether concentric, but not
      nonconcentric, Glass patterns (a type of form-from-structure stimulus) utilize a
      processing mechanism shared by face perception. For the adaptation experiments,
      subjects were presented with an adaptor for 5 or 20 s, prior to discriminating a
      target. In the masking experiments, subjects saw a mask, then a target, and then
      a second mask. Measures of discriminability and bias were derived and repeated
      measures analysis of variance tested for pattern-specific masking and adaptation
      effects. Results from Experiment 1 show no Glass pattern-specific effect of
      adaptation to faces; results from Experiment 2 show concentric Glass pattern
      masking, but not adaptation, may impair upright/inverted face discrimination;
      results from Experiment 3 show concentric and radial Glass pattern masking
      impaired subsequent upright/inverted face discrimination more than translational
      Glass pattern masking; and results from Experiment 4 show concentric and radial
      Glass pattern masking impaired subsequent face gender discrimination more than
      translational Glass pattern masking. Taken together, these findings demonstrate
      interactions between concentric form-from-structure and face processing,
      suggesting a possible common processing pathway. 

PMID- 24563528
TI  - Variety in emotional life: within-category typicality of emotional experiences is
      associated with neural activity in large-scale brain networks.
AB  - The tremendous variability within categories of human emotional experience
      receives little empirical attention. We hypothesized that atypical instances of
      emotion categories (e.g. pleasant fear of thrill-seeking) would be processed less
      efficiently than typical instances of emotion categories (e.g. unpleasant fear of
      violent threat) in large-scale brain networks. During a novel fMRI paradigm,
      participants immersed themselves in scenarios designed to induce atypical and
      typical experiences of fear, sadness or happiness (scenario immersion), and then
      focused on and rated the pleasant or unpleasant feeling that emerged (valence
      focus) in most trials. As predicted, reliably greater activity in the 'default
      mode' network (including medial prefrontal cortex and posterior cingulate) was
      observed for atypical (vs typical) emotional experiences during scenario
      immersion, suggesting atypical instances require greater conceptual processing to
      situate the socio-emotional experience. During valence focus, reliably greater
      activity was observed for atypical (vs typical) emotional experiences in the
      'salience' network (including anterior insula and anterior cingulate), suggesting
      atypical instances place greater demands on integrating shifting body signals
      with the sensory and social context. Consistent with emerging psychological
      construction approaches to emotion, these findings demonstrate that is it
      important to study the variability within common categories of emotional
      experience. 

PMID- 24563529
TI  - Empathy for social exclusion involves the sensory-discriminative component of
      pain: a within-subject fMRI study.
AB  - Recent research has shown that experiencing events that represent a significant
      threat to social bonds activates a network of brain areas associated with the
      sensory-discriminative aspects of pain. In the present study, we investigated
      whether the same brain areas are involved when witnessing social exclusion
      threats experienced by others. Using a within-subject design, we show that an
      ecologically valid experience of social exclusion recruits areas coding the
      somatosensory components of physical pain (posterior insular cortex and secondary
      somatosensory cortex). Furthermore, we show that this pattern of activation not
      only holds for directly experienced social pain, but also during empathy for
      social pain. Finally, we report that subgenual cingulate cortex is the only brain
      area conjointly active during empathy for physical and social pain. This supports
      recent theories that affective processing and homeostatic regulation are at the
      core of empathic responses. 

PMID- 24563530
TI  - Arginase inhibition prevents inflammation and remodeling in a guinea pig model of
      chronic obstructive pulmonary disease.
AB  - Airway inflammation and remodeling are major features of chronic obstructive
      pulmonary disease (COPD), whereas pulmonary hypertension is a common comorbidity
      associated with a poor disease prognosis. Recent studies in animal models have
      indicated that increased arginase activity contributes to features of asthma,
      including allergen-induced airway eosinophilia and mucus hypersecretion. Although
      cigarette smoke and lipopolysaccharide (LPS), major risk factors for COPD, may
      increase arginase expression, the role of arginase in COPD is unknown. This study
      aimed to investigate the role of arginase in pulmonary inflammation and
      remodeling using an animal model of COPD. Guinea pigs were instilled intranasally
      with LPS or saline twice weekly for 12 weeks and pretreated by inhalation of the
      arginase inhibitor 2(S)-amino-6-boronohexanoic acid (ABH) or vehicle. Repeated
      LPS exposure increased lung arginase activity, resulting in increased l
      ornithine/l-arginine and l-ornithine/l-citrulline ratios. Both ratios were
      reversed by ABH. ABH inhibited the LPS-induced increases in pulmonary IL-8,
      neutrophils, and goblet cells as well as airway fibrosis. Remarkably, LPS-induced
      right ventricular hypertrophy, indicative of pulmonary hypertension, was
      prevented by ABH. Strong correlations were found between arginase activity and
      inflammation, airway remodeling, and right ventricular hypertrophy. Increased
      arginase activity contributes to pulmonary inflammation, airway remodeling, and
      right ventricular hypertrophy in a guinea pig model of COPD, indicating
      therapeutic potential for arginase inhibitors in this disease. 

PMID- 24563532
TI  - Radiation therapy for carcinoma of the uterine cervix: comparison of two
      brachytherapy schedules.
AB  - We compared the survival rates and late effects for two groups of cervical cancer
      patients treated with almost the same external radiotherapy but different remote
      afterloading systems (RALS) for high-dose-rate intracavitary radiation therapy
      regimens. A total of 218 patients with carcinoma of the uterine cervix were
      treated. For 98 patients, intracavitary brachytherapy was delivered with 6-7.5
      Gy/fraction to Point A (Group A), and for 120, 5 Gy/fraction with a modified
      source step size (Group B). The 3-year cause-specific survival rates by stage and
      treatment schedule were Group A: 91% and Group B: 96% in Stage I, 89% and 92% in
      Stage II, 64% and 75% in Stage III, 44% and 69% in Stage IV. The survival curves
      did not reveal any statistically significant differences at any stage. The 3-year
      cumulative local failure rates were 14% in Group A and 7% in Group B (P =
      0.1202), while the actuarial rates of developing rectal complication (Grade 2 or
      more) at 3 years were 25% in Group A and 4% in Group B (P < 0.0001). This
      retrospective analysis suggests that a low dose per fraction with modified source
      step size is advantageous because of yielding almost the same local control but
      with fewer rectal complications.

PMID- 24563531
TI  - A novel aminotetralin-type serotonin (5-HT) 2C receptor-specific agonist and 5
      HT2A competitive antagonist/5-HT2B inverse agonist with preclinical efficacy for
      psychoses.
AB  - Development of 5-HT2C agonists for treatment of neuropsychiatric disorders,
      including psychoses, substance abuse, and obesity, has been fraught with
      difficulties, because the vast majority of reported 5-HT2C selective agonists
      also activate 5-HT2A and/or 5-HT2B receptors, potentially causing hallucinations
      and/or cardiac valvulopathy. Herein is described a novel, potent, and efficacious
      human 5-HT2C receptor agonist, (-)-trans-(2S,4R)-4-(3'[meta]-bromophenyl)-N,N
      dimethyl-1,2,3,4-tetrahydronaphthalen-2-amine (-)-MBP), that is a competitive
      antagonist and inverse agonist at human 5-HT2A and 5-HT2B receptors,
      respectively. (-)-MBP has efficacy comparable to the prototypical second
      generation antipsychotic drug clozapine in three C57Bl/6 mouse models of drug
      induced psychoses: the head-twitch response elicited by [2,5]-dimethoxy-4
      iodoamphetamine; hyperlocomotion induced by MK-801 [(5R,10S)-(+)-5-methyl-10,11
      dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate (dizocilpine
      maleate)]; and hyperlocomotion induced by amphetamine. (-)-MBP, however, does not
      alter locomotion when administered alone, distinguishing it from clozapine, which
      suppresses locomotion. Finally, consumption of highly palatable food by mice was
      not increased by (-)-MBP at a dose that produced at least 50% maximal efficacy in
      the psychoses models. Compared with (-)-MBP, the enantiomer (+)-MBP was much less
      active across in vitro affinity and functional assays using mouse and human
      receptors and also translated in vivo with comparably lower potency and efficacy.
      Results indicate a 5-HT2C receptor-specific agonist, such as (-)-MBP, may be
      pharmacotherapeutic for psychoses, without liability for obesity, hallucinations,
      heart disease, sedation, or motoric disorders. 

PMID- 24563533
TI  - Elution profile analysis of SDS-induced subcomplexes by quantitative mass
      spectrometry.
AB  - Analyzing the molecular architecture of native multiprotein complexes via
      biochemical methods has so far been difficult and error prone. Protein complex
      isolation by affinity purification can define the protein repertoire of a given
      complex, yet, it remains difficult to gain knowledge of its substructure or
      modular composition. Here, we introduce SDS concentration gradient induced
      decomposition of protein complexes coupled to quantitative mass spectrometry and
      in silico elution profile distance analysis. By applying this new method to a
      cellular transport module, the IFT/lebercilin complex, we demonstrate its ability
      to determine modular composition as well as sensitively detect known and novel
      complex components. We show that the IFT/lebercilin complex can be separated into
      at least five submodules, the IFT complex A, the IFT complex B, the 14-3-3
      protein complex and the CTLH complex, as well as the dynein light chain complex.
      Furthermore, we identify the protein TULP3 as a potential new member of the IFT
      complex A and showed that several proteins, classified as IFT complex B
      associated, are integral parts of this complex. To further demonstrate EPASIS
      general applicability, we analyzed the modular substructure of two additional
      complexes, that of B-RAF and of 14-3-3-epsilon. The results show, that EPASIS
      provides a robust as well as sensitive strategy to dissect the substructure of
      large multiprotein complexes in a highly time- as well as cost-effective manner. 

PMID- 24563535
TI  - Improved normalization of systematic biases affecting ion current measurements in
      label-free proteomics data.
AB  - Normalization is an important step in the analysis of quantitative proteomics
      data. If this step is ignored, systematic biases can lead to incorrect
      assumptions about regulation. Most statistical procedures for normalizing
      proteomics data have been borrowed from genomics where their development has
      focused on the removal of so-called 'batch effects.' In general, a typical
      normalization step in proteomics works under the assumption that most
      peptides/proteins do not change; scaling is then used to give a median log-ratio
      of 0. The focus of this work was to identify other factors, derived from
      knowledge of the variables in proteomics, which might be used to improve
      normalization. Here we have examined the multi-laboratory data sets from Phase I
      of the NCI's CPTAC program. Surprisingly, the most important bias variables
      affecting peptide intensities within labs were retention time and charge state.
      The magnitude of these observations was exaggerated in samples of unequal
      concentrations or "spike-in" levels, presumably because the average precursor
      charge for peptides with higher charge state potentials is lower at higher
      relative sample concentrations. These effects are consistent with reduced
      protonation during electrospray and demonstrate that the physical properties of
      the peptides themselves can serve as good reporters of systematic biases. Between
      labs, retention time, precursor m/z, and peptide length were most commonly the
      top-ranked bias variables, over the standardly used average intensity (A). A
      larger set of variables was then used to develop a stepwise normalization
      procedure. This statistical model was found to perform as well or better on the
      CPTAC mock biomarker data than other commonly used methods. Furthermore, the
      method described here does not require a priori knowledge of the systematic
      biases in a given data set. These improvements can be attributed to the inclusion
      of variables other than average intensity during normalization. 

PMID- 24563534
TI  - Proteomic analysis of arginine methylation sites in human cells reveals dynamic
      regulation during transcriptional arrest.
AB  - The covalent attachment of methyl groups to the side-chain of arginine residues
      is known to play essential roles in regulation of transcription, protein
      function, and RNA metabolism. The specific N-methylation of arginine residues is
      catalyzed by a small family of gene products known as protein arginine
      methyltransferases; however, very little is known about which arginine residues
      become methylated on target substrates. Here we describe a proteomics methodology
      that combines single-step immunoenrichment of methylated peptides with high
      resolution mass spectrometry to identify endogenous arginine mono-methylation
      (MMA) sites. We thereby identify 1027 site-specific MMA sites on 494 human
      proteins, discovering numerous novel mono-methylation targets and confirming the
      majority of currently known MMA substrates. Nuclear RNA-binding proteins involved
      in RNA processing, RNA localization, transcription, and chromatin remodeling are
      predominantly found modified with MMA. Despite this, MMA sites prominently are
      located outside RNA-binding domains as compared with the proteome-wide
      distribution of arginine residues. Quantification of arginine methylation in
      cells treated with Actinomycin D uncovers strong site-specific regulation of MMA
      sites during transcriptional arrest. Interestingly, several MMA sites are down
      regulated after a few hours of transcriptional arrest. In contrast, the
      corresponding di-methylation or protein expression levels are not altered,
      confirming that MMA sites contain regulated functions on their own. Collectively,
      we present a site-specific MMA data set in human cells and demonstrate for the
      first time that MMA is a dynamic post-translational modification regulated during
      transcriptional arrest by a hitherto uncharacterized arginine demethylase. 

PMID- 24563536
TI  - Quantitative, time-resolved proteomic analysis by combining bioorthogonal
      noncanonical amino acid tagging and pulsed stable isotope labeling by amino acids
      in cell culture.
AB  - An approach to proteomic analysis that combines bioorthogonal noncanonical amino
      acid tagging (BONCAT) and pulsed stable isotope labeling with amino acids in cell
      culture (pSILAC) provides accurate quantitative information about rates of
      cellular protein synthesis on time scales of minutes. The method is capable of
      quantifying 1400 proteins produced by HeLa cells during a 30 min interval, a time
      scale that is inaccessible to isotope labeling techniques alone. Potential
      artifacts in protein quantification can be reduced to insignificant levels by
      limiting the extent of noncanonical amino acid tagging. We find no evidence for
      artifacts in protein identification in experiments that combine the BONCAT and
      pSILAC methods. 

PMID- 24563539
TI  - Selective inhibition of EZH2 by EPZ-6438 leads to potent antitumor activity in
      EZH2-mutant non-Hodgkin lymphoma.
AB  - Mutations within the catalytic domain of the histone methyltransferase EZH2 have
      been identified in subsets of patients with non-Hodgkin lymphoma (NHL). These
      genetic alterations are hypothesized to confer an oncogenic dependency on EZH2
      enzymatic activity in these cancers. We have previously reported the discovery of
      EPZ005678 and EPZ-6438, potent and selective S-adenosyl-methionine-competitive
      small molecule inhibitors of EZH2. Although both compounds are similar with
      respect to their mechanism of action and selectivity, EPZ-6438 possesses superior
      potency and drug-like properties, including good oral bioavailability in animals.
      Here, we characterize the activity of EPZ-6438 in preclinical models of NHL. EPZ
      6438 selectively inhibits intracellular lysine 27 of histone H3 (H3K27)
      methylation in a concentration- and time-dependent manner in both EZH2 wild-type
      and mutant lymphoma cells. Inhibition of H3K27 trimethylation (H3K27Me3) leads to
      selective cell killing of human lymphoma cell lines bearing EZH2 catalytic domain
      point mutations. Treatment of EZH2-mutant NHL xenograft-bearing mice with EPZ
      6438 causes dose-dependent tumor growth inhibition, including complete and
      sustained tumor regressions with correlative diminution of H3K27Me3 levels in
      tumors and selected normal tissues. Mice dosed orally with EPZ-6438 for 28 days
      remained tumor free for up to 63 days after stopping compound treatment in two
      EZH2-mutant xenograft models. These data confirm the dependency of EZH2-mutant
      NHL on EZH2 activity and portend the utility of EPZ-6438 as a potential treatment
      for these genetically defined cancers.

PMID- 24563541
TI  - Birinapant (TL32711), a bivalent SMAC mimetic, targets TRAF2-associated cIAPs,
      abrogates TNF-induced NF-kappaB activation, and is active in patient-derived
      xenograft models.
AB  - The acquisition of apoptosis resistance is a fundamental event in cancer
      development. Among the mechanisms used by cancer cells to evade apoptosis is the
      dysregulation of inhibitor of apoptosis (IAP) proteins. The activity of the IAPs
      is regulated by endogenous IAP antagonists such as SMAC (also termed DIABLO).
      Antagonism of IAP proteins by SMAC occurs via binding of the N-terminal
      tetrapeptide (AVPI) of SMAC to selected BIR domains of the IAPs. Small molecule
      compounds that mimic the AVPI motif of SMAC have been designed to overcome IAP
      mediated apoptosis resistance of cancer cells. Here, we report the preclinical
      characterization of birinapant (TL32711), a bivalent SMAC-mimetic compound
      currently in clinical trials for the treatment of cancer. Birinapant bound to the
      BIR3 domains of cIAP1, cIAP2, XIAP, and the BIR domain of ML-IAP in vitro and
      induced the autoubiquitylation and proteasomal degradation of cIAP1 and cIAP2 in
      intact cells, which resulted in formation of a RIPK1:caspase-8 complex, caspase-8
      activation, and induction of tumor cell death. Birinapant preferentially targeted
      the TRAF2-associated cIAP1 and cIAP2 with subsequent inhibition of TNF-induced NF
      kappaB activation. The activity of a variety of chemotherapeutic cancer drugs was
      potentiated by birinapant both in a TNF-dependent or TNF-independent manner.
      Tumor growth in multiple primary patient-derived xenotransplant models was
      inhibited by birinapant at well-tolerated doses. These results support the
      therapeutic combination of birinapant with multiple chemotherapies, in
      particular, those therapies that can induce TNF secretion.

PMID- 24563540
TI  - The phosphoinositide 3-kinase alpha selective inhibitor BYL719 enhances the
      effect of the protein kinase C inhibitor AEB071 in GNAQ/GNA11-mutant uveal
      melanoma cells.
AB  - G-protein mutations are one of the most common mutations occurring in uveal
      melanoma activating the protein kinase C (PKC)/mitogen-activated protein kinase
      and phosphoinositide 3-kinase (PI3K)/AKT pathways. In this study, we described
      the effect of dual pathway inhibition in uveal melanoma harboring GNAQ and GNA11
      mutations via PKC inhibition with AEB071 (sotrastaurin) and PI3K/AKT inhibition
      with BYL719, a selective PI3Kalpha inhibitor. Growth inhibition was observed in
      GNAQ/GNA11-mutant cells with AEB071 versus no activity in wild-type cells. In the
      GNAQ-mutant cells, AEB071 decreased phosphorylation of myristoylated alanine-rich
      C-kinase substrate, a substrate of PKC, along with ERK1/2 and ribosomal S6, but
      persistent AKT activation was present. BYL719 had minimal antiproliferative
      activity in all uveal melanoma cell lines, and inhibited phosphorylation of AKT
      in most cell lines. In the GNA11-mutant cell line, similar effects were observed
      with ERK1/2 inhibition, mostly inhibited by BYL719. With the combination
      treatment, both GNAQ- and GNA11-mutant cell lines showed synergistic inhibition
      of cell proliferation and apoptotic cell death. In vivo studies correlated with
      in vitro findings showing reduced xenograft tumor growth with the combination
      therapy in a GNAQ-mutant model. These findings suggest a new therapy treatment
      option for G-protein-mutant uveal melanoma with a focus on specific targeting of
      multiple downstream pathways as part of combination therapy.

PMID- 24563543
TI  - Evaluation of the stability of an SR398/GroES chaperonin complex.
AB  - The stability of an SR398/GroES chaperonin complex was examined. As was expected,
      based on the finding of previous studies, the SR398/GroES complex was extremely
      stable in the presence of an excess amount of free adenosine 5'-[gamma
      thio]triphosphate (ATPgammaS) or adenosine 5'-(beta,gamma-imido)triphosphate
      (AMPPNP). However, the complex was not stable in the absence of nucleotides.
      These results indicate that ATPgammaS and AMPPNP repeatedly associated to and
      dissociated from the complex in a non-cooperative manner. This nucleotide
      exchange did not induce the dissociation of GroES and substrate from SR398,
      suggesting the importance of the cooperative dissociation of nucleotides from the
      cis-ring to release GroES and substrate proteins in the GroEL/GroES reaction
      cycle. 

PMID- 24563542
TI  - Aurora kinase inhibition induces PUMA via NF-kappaB to kill colon cancer cells.
AB  - Aurora kinases play a key role in mitosis and are frequently overexpressed in a
      variety of tumor cells. Inhibition of aurora kinases results in mitotic arrest
      and death of cancer cells, and has been explored as an anticancer strategy.
      However, how aurora inhibition kills cancer cells is poorly understood. In this
      study, we found that inhibition of aurora kinases by siRNA or small-molecule
      inhibitors led to induction of p53 upregulated modulator of apoptosis (PUMA), a
      BH3-only Bcl-2 family protein, in colorectal cancer cells irrespective of p53
      status. Deficiency in PUMA increased polyploidy, improved cell survival, and
      abrogated mitochondria-mediated apoptosis induced by aurora kinase inhibitors. In
      response to aurora kinase inhibition, PUMA was directly activated by p65 through
      the canonical NF-kappaB pathway following AKT inhibition. Furthermore, PUMA was
      necessary for the chemosensitization and in vivo antitumor effects of aurora
      kinase inhibitors in colon cancer cells. These results suggest that PUMA
      induction mediates the apoptotic response to mitotic arrest imposed by aurora
      kinase inhibition, and may be a useful indicator for the anticancer activity of
      aurora kinase inhibitors.

PMID- 24563544
TI  - Identifying barbiturate binding sites in a nicotinic acetylcholine receptor with
      [3H]allyl m-trifluoromethyldiazirine mephobarbital, a photoreactive barbiturate.
AB  - At concentrations that produce anesthesia, many barbituric acid derivatives act
      as positive allosteric modulators of inhibitory GABAA receptors (GABAARs) and
      inhibitors of excitatory nicotinic acetylcholine receptors (nAChRs). Recent
      research on [(3)H]R-mTFD-MPAB ([(3)H]R-5-allyl-1-methyl-5-(m
      trifluoromethyldiazirinylphenyl)barbituric acid), a photoreactive barbiturate
      that is a potent and stereoselective anesthetic and GABAAR potentiator, has
      identified a second class of intersubunit binding sites for general anesthetics
      in the alpha1beta3gamma2 GABAAR transmembrane domain. We now characterize mTFD
      MPAB interactions with the Torpedo (muscle-type) nAChR. For nAChRs expressed in
      Xenopus oocytes, S- and R-mTFD-MPAB inhibited ACh-induced currents with IC50
      values of 5 and 10 uM, respectively. Racemic mTFD-MPAB enhanced the equilibrium
      binding of [(3)H]ACh to nAChR-rich membranes (EC50 = 9 uM) and inhibited binding
      of the ion channel blocker [(3)H]tenocyclidine in the nAChR desensitized and
      resting states with IC50 values of 2 and 170 uM, respectively. Photoaffinity
      labeling identified two binding sites for [(3)H]R-mTFD-MPAB in the nAChR
      transmembrane domain: 1) a site within the ion channel, identified by
      photolabeling in the nAChR desensitized state of amino acids within the M2
      helices of each nAChR subunit; and 2) a site at the gamma-alpha subunit
      interface, identified by photolabeling of gammaMet299 within the gammaM3 helix at
      similar efficiency in the resting and desensitized states. These results
      establish that mTFD-MPAB is a potent nAChR inhibitor that binds in the ion
      channel preferentially in the desensitized state and binds with lower affinity to
      a site at the gamma-alpha subunit interface where etomidate analogs bind that act
      as positive and negative nAChR modulators. 

PMID- 24563547
TI  - MESAFace, a graphical interface to analyze the MESA output.
AB  - : MESA (Modules for Experiments in Stellar Astrophysics) has become very popular
      among astrophysicists as a powerful and reliable code to simulate stellar
      evolution. Analyzing the output data thoroughly may, however, present some
      challenges and be rather time-consuming. Here we describe MESAFace, a graphical
      and dynamical interface which provides an intuitive, efficient and quick way to
      analyze the MESA output. NATURE OF PROBLEM: Find a way to quickly and thoroughly
      analyze the output of a MESA run, including all the profiles, and have an
      efficient method to produce graphical representations of the data. SOLUTION
      METHOD: We created two scripts (to be run consecutively). The first one downloads
      all the data from a MESA run and organizes the profiles in order of age. All the
      files are saved as tables or arrays of tables which can then be accessed very
      quickly by Mathematica. The second script uses the Manipulate function to create
      a graphical interface which allows the user to choose what to plot from a set of
      menus and buttons. The information shown is updated in real time. The user can
      access very quickly all the data from the run under examination and visualize it
      with plots and tables. UNUSUAL FEATURES: Moving the slides in certain regions may
      cause an error message. This happens when Mathematica is asked to read
      nonexistent data. The error message, however, disappears when the slides are
      moved back. This issue does not preclude the good functioning of the interface.
      ADDITIONAL COMMENTS: The program uses the dynamical capabilities of Mathematica.
      When the program is opened, Mathematica prompts the user to "Enable Dynamics". It
      is necessary to accept before proceeding. RUNNING TIME: Depends on the size of
      the data downloaded, on where the data are stored (hard-drive or web), and on the
      speed of the computer or network connection. In general, downloading the data may
      take from a minute to several minutes. Loading directly from the web is slower.
      For example, downloading a 200MB data folder (a total of 102 files) with a dual
      core Intel laptop, P8700, 2 GB of RAM, at 2.53 GHz took about a minute from the
      hard-drive and about 23 minutes from the web (with a basic home wireless
      connection).

PMID- 24563545
TI  - Microbiome-derived tryptophan metabolites and their aryl hydrocarbon receptor
      dependent agonist and antagonist activities.
AB  - The tryptophan metabolites indole, indole-3-acetate, and tryptamine were
      identified in mouse cecal extracts and fecal pellets by mass spectrometry. The
      aryl hydrocarbon receptor (AHR) agonist and antagonist activities of these
      microbiota-derived compounds were investigated in CaCo-2 intestinal cells as a
      model for understanding their interactions with colonic tissue, which is highly
      aryl hydrocarbon (Ah)-responsive. Activation of Ah-responsive genes demonstrated
      that tryptamine and indole 3-acetate were AHR agonists, whereas indole was an AHR
      antagonist that inhibited TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin)-induced
      CYP1A1 expression. In contrast, the tryptophan metabolites exhibited minimal anti
      inflammatory activities, whereas TCDD decreased phorbol ester-induced CXCR4
      [chemokine (C-X-C motif) receptor 4] gene expression, and this response was AHR
      dependent. These results demonstrate that the tryptophan metabolites indole,
      tryptamine, and indole-3-acetate modulate AHR-mediated responses in CaCo-2 cells,
      and concentrations of indole that exhibit AHR antagonist activity (100-250 MUM)
      are detected in the intestinal microbiome. 

PMID- 24563546
TI  - Block of human cardiac sodium channels by lacosamide: evidence for slow drug
      binding along the activation pathway.
AB  - Lacosamide is an anticonvulsant hypothesized to enhance slow inactivation of
      neuronal Na(+) channels for its therapeutic action. Cardiac Na(+) channels
      display less and incomplete slow inactivation, but their sensitivity toward
      lacosamide remains unknown. We therefore investigated the action of lacosamide in
      human cardiac Nav1.5 and Nav1.5-CW inactivation-deficient Na(+) channels.
      Lacosamide showed little effect on hNav1.5 Na(+) currents at 300 uM when cells
      were held at -140 mV. With 30-second conditioning pulses from -90 to -50 mV;
      however, hNav1.5 Na(+) channels became sensitive to lacosamide with IC50 (50%
      inhibitory concentration) around 70-80 uM. Higher IC50 values were found at -110
      and -30 mV. The development of lacosamide block at -70 mV was slow in wild-type
      Na(+) channels (tau; 8.04 +/- 0.39 seconds, n = 8). This time constant was
      significantly accelerated in hNav1.5-CW inactivation-deficient counterparts. The
      recovery from lacosamide block at -70 mV for 10 seconds was relatively rapid in
      wild-type Na(+) channels (tau; 639 +/- 90 milliseconds, n = 8). This recovery was
      accelerated further in hNav1.5-CW counterparts. Unexpectedly, lacosamide elicited
      a time-dependent block of persistent hNav1.5-CW Na(+) currents with an IC50 of
      242 +/- 19 uM (n = 5). Furthermore, both hNav1.5-CW/F1760K mutant and
      batrachotoxin-activated hNav1.5 Na(+) channels became completely lacosamide
      resistant, indicating that the lacosamide receptor overlaps receptors for local
      anesthetics and batrachotoxin. Our results together suggest that lacosamide
      targets the intermediate preopen and open states of hNav1.5 Na(+) channels.
      Lacosamide may thus track closely the conformational changes at the hNav1.5-F1760
      region along the activation pathway. 

PMID- 24563548
TI  - Singular perturbation theory for predicting extravasation of Brownian particles.
AB  - Motivated by recent studies on tumor treatments using the drug delivery of
      nanoparticles, we provide a singular perturbation theory and perform Brownian
      dynamics simulations to quantify the extravasation rate of Brownian particles in
      a shear flow over a circular pore with a lumped mass transfer resistance. The
      analytic theory we present is an expansion in the limit of a vanishing Peclet
      number (P), which is the ratio of convective fluxes to diffusive fluxes on the
      length scale of the pore. We state the concentration of particles near the pore
      and the extravasation rate (Sherwood number) to O(P1/2). This model improves upon
      previous studies because the results are valid for all values of the particle
      mass transfer coefficient across the pore, as modeled by the Damkohler number
      (kappa), which is the ratio of the reaction rate to the diffusive mass transfer
      rate at the boundary. Previous studies focused on the adsorption-dominated regime
      (i.e., kappa -> infinity). Specifically, our work provides a theoretical basis
      and an interpolation-based approximate method for calculating the Sherwood number
      (a measure of the extravasation rate) for the case of finite resistance [kappa ~
      O(1)] at small Peclet numbers, which are physiologically important in the
      extravasation of nanoparticles. We compare the predictions of our theory and an
      approximate method to Brownian dynamics simulations with reflection-reaction
      boundary conditions as modeled by kappa. They are found to agree well at small P
      and for the kappa ? 1 and kappa ? 1 asymptotic limits representing the diffusion
      dominated and adsorption-dominated regimes, respectively. Although this model
      neglects the finite size effects of the particles, it provides an important first
      step toward understanding the physics of extravasation in the tumor vasculature.

PMID- 24563549
TI  - The Role of Cohabitation in Family Formation: The United States in Comparative
      Perspective.
AB  - The prevalence of nonmarital cohabitation is steadily increasing in the United
      States. In evaluating the contribution of this new living arrangement to family
      formation, analysts have relied primarily on comparisons between individuals who
      cohabit and those who do not. We complement this line of inquiry by comparing the
      United States and 16 industrialized nations. We first identify six conceptually
      distinct ideal types of cohabitation with respect to family formation. We then
      propose empirical indicators to distinguish between the different ideal types,
      and estimate the values of these indicators for each of the 17 nations. Our
      findings indicate that although a number of countries fit an empirical pattern
      corresponding to one ideal type, cohabitation in the United States is more
      difficult to characterize.

PMID- 24563550
TI  - It Takes a Village (Perhaps a Nation): Families, States, and Educational
      Achievement.
AB  - Research in the United States has shown that children growing up in 2-parent
      households do better in school than children from single-parent households. We
      used the Trends in International Mathematics and Science Study (TIMSS) data to
      test whether this finding applied to other countries as well (N = 100,307). We
      found that it did, but that the educational gap was greater in the United States
      than in the other 13 countries considered. Results from 2-level hierarchical
      linear models demonstrated that international differences in the educational gap
      were associated with several indicators of national policy and demographic
      contexts. No single policy appeared to have a large effect, but several policy
      combinations were associated with substantially reduced educational gaps between
      children from different family structures.

PMID- 24563551
TI  - On the mechanics of growing thin biological membranes.
AB  - Despite their seemingly delicate appearance, thin biological membranes fulfill
      various crucial roles in the human body and can sustain substantial mechanical
      loads. Unlike engineering structures, biological membranes are able to grow and
      adapt to changes in their mechanical environment. Finite element modeling of
      biological growth holds the potential to better understand the interplay of
      membrane form and function and to reliably predict the effects of disease or
      medical intervention. However, standard continuum elements typically fail to
      represent thin biological membranes efficiently, accurately, and robustly.
      Moreover, continuum models are typically cumbersome to generate from surface
      based medical imaging data. Here we propose a computational model for finite
      membrane growth using a classical midsurface representation compatible with
      standard shell elements. By assuming elastic incompressibility and membrane-only
      growth, the model a priori satisfies the zero-normal stress condition. To
      demonstrate its modular nature, we implement the membrane growth model into the
      general-purpose non-linear finite element package Abaqus/Standard using the
      concept of user subroutines. To probe efficiently and robustness, we simulate
      selected benchmark examples of growing biological membranes under different
      loading conditions. To demonstrate the clinical potential, we simulate the
      functional adaptation of a heart valve leaflet in ischemic cardiomyopathy. We
      believe that our novel approach will be widely applicable to simulate the
      adaptive chronic growth of thin biological structures including skin membranes,
      mucous membranes, fetal membranes, tympanic membranes, corneoscleral membranes,
      and heart valve membranes. Ultimately, our model can be used to identify diseased
      states, predict disease evolution, and guide the design of interventional or
      pharmaceutic therapies to arrest or revert disease progression.

PMID- 24563552
TI  - Injectable PolyMIPE Scaffolds for Soft Tissue Regeneration.
AB  - Injury caused by trauma, burns, surgery, or disease often results in soft tissue
      loss leading to impaired function and permanent disfiguration. Tissue engineering
      aims to overcome the lack of viable donor tissue by fabricating synthetic
      scaffolds with the requisite properties and bioactive cues to regenerate these
      tissues. Biomaterial scaffolds designed to match soft tissue modulus and strength
      should also retain the elastomeric and fatigue-resistant properties of the
      tissue. Of particular design importance is the interconnected porous structure of
      the scaffold needed to support tissue growth by facilitating mass transport.
      Adequate mass transport is especially true for newly implanted scaffolds that
      lack vasculature to provide nutrient flux. Common scaffold fabrication strategies
      often utilize toxic solvents and high temperatures or pressures to achieve the
      desired porosity. In this study, a polymerized medium internal phase emulsion
      (polyMIPE) is used to generate an injectable graft that cures to a porous foam at
      body temperature without toxic solvents. These poly(ester urethane urea)
      scaffolds possess elastomeric properties with tunable compressive moduli (20-200
      kPa) and strengths (4-60 kPa) as well as high recovery after the first
      conditioning cycle (97-99%). The resultant pore architecture was highly
      interconnected with large voids (0.5-2 mm) from carbon dioxide generation
      surrounded by water-templated pores (50-300 MUm). The ability to modulate both
      scaffold pore architecture and mechanical properties by altering emulsion
      chemistry was demonstrated. Permeability and form factor were experimentally
      measured to determine the effects of polyMIPE composition on pore
      interconnectivity. Finally, initial human mesenchymal stem cell (hMSC)
      cytocompatibility testing supported the use of these candidate scaffolds in
      regenerative applications. Overall, these injectable polyMIPE foams show strong
      promise as a biomaterial scaffold for soft tissue repair.

PMID- 24563554
TI  - Racial and Social Class Differences in How Parents Respond to Inadequate
      Achievement: Consequences for Children's Future Achievement.
AB  - OBJECTIVE: Despite numerous studies on parental involvement in children's
      academic schooling, there is a dearth of knowledge on how parents respond
      specifically to inadequate academic performance. This study examines whether 1)
      racial differences exist in parenting philosophy for addressing inadequate
      achievement, 2) social class has implications for parenting philosophy, and 3)
      parents' philosophies are consequential for children's academic achievement.
      METHODS: Using data from the Child Development Supplement (N=1041) to the Panel
      Study of Income Dynamics, we sort parents into two categories-those whose
      parenting repertoires for addressing poor achievement include punitive responses
      and those whose repertoires do not. We then determine whether racial differences
      exist between these categories and how various responses within the
      aforementioned categories are related to students' academic achievement. RESULTS:
      The findings show that white and black parents have markedly different
      philosophies on how to respond to inadequate performance, and these differences
      appear to impact children's achievement in dramatically different ways.
      CONCLUSION: Educators and policy makers should pay particular attention to how
      parents respond to inadequate achievement as imploring parents of inadequately
      performing students to be more involved without providing them with some guidance
      might exacerbate the problem.

PMID- 24563553
TI  - Predictors of Early Reading Skill in 5-Year-Old Children With Hearing Loss Who
      Use Spoken Language.
AB  - This research investigated the concurrent association between early reading
      skills and phonological awareness (PA), print knowledge, language, cognitive, and
      demographic variables in 101 5-year-old children with prelingual hearing losses
      ranging from mild to profound who communicated primarily using spoken language.
      All participants were fitted with hearing aids (n = 71) or cochlear implants (n =
      30). They completed standardized assessments of PA, receptive vocabulary, letter
      knowledge, word and non-word reading, passage comprehension, math reasoning, and
      nonverbal cognitive ability. Multiple regressions revealed that PA (assessed
      using judgments of similarity based on words' initial or final sounds) made a
      significant, independent contribution to children's early reading ability (for
      both letters and words/non-words) after controlling for variation in receptive
      vocabulary, nonverbal cognitive ability, and a range of demographic variables
      (including gender, degree of hearing loss, communication mode, type of sensory
      device, age at fitting of sensory devices, and level of maternal education).
      Importantly, the relationship between PA and reading was specific to reading and
      did not generalize to another academic ability, math reasoning. Additional
      multiple regressions showed that letter knowledge (names or sounds) was superior
      in children whose mothers had undertaken post-secondary education, and that
      better receptive vocabulary was associated with less severe hearing loss, use of
      a cochlear implant, and earlier age at implant switch-on. Earlier fitting of
      hearing aids or cochlear implants was not, however, significantly associated with
      better PA or reading outcomes in this cohort of children, most of whom were
      fitted with sensory devices before 3 years of age.

PMID- 24563555
TI  - Boc-protected 1-(3-oxocycloalkyl)ureas via a one-step Curtius rearrangement:
      mechanism and scope.
AB  - 1-(3-Oxocyclobutyl) carboxylic acid (4a) was converted into N-Boc-protected 1-(3
      oxocyclobutyl) urea (5a), a key intermediates for the preparation of agonists of
      metabotropic glutamate receptor 5, in one-step when treated with diphenyl
      phosphoryl azide and triethylamine in tert-butanol. The mechanism of the reaction
      involves a nucleophilic addition of the in situ generated tert-butyl carbamate to
      the isocyanate intermediate. This reaction is applicable to other 1-(3
      oxocycloalkyl) carboxylic acids but not to linear gamma-keto carboxylic acids.

PMID- 24563556
TI  - Characteristic mega-basin water storage behavior using GRACE.
AB  - [1] A long-standing challenge for hydrologists has been a lack of observational
      data on global-scale basin hydrological behavior. With observations from NASA's
      Gravity Recovery and Climate Experiment (GRACE) mission, hydrologists are now
      able to study terrestrial water storage for large river basins (>200,000 km2),
      with monthly time resolution. Here we provide results of a time series model of
      basin-averaged GRACE terrestrial water storage anomaly and Global Precipitation
      Climatology Project precipitation for the world's largest basins. We address the
      short (10 year) length of the GRACE record by adopting a parametric spectral
      method to calculate frequency-domain transfer functions of storage response to
      precipitation forcing and then generalize these transfer functions based on large
      scale basin characteristics, such as percent forest cover and basin temperature.
      Among the parameters tested, results show that temperature, soil water-holding
      capacity, and percent forest cover are important controls on relative storage
      variability, while basin area and mean terrain slope are less important. The
      derived empirical relationships were accurate (0.54 <= Ef  <= 0.84) in modeling
      global-scale water storage anomaly time series for the study basins using only
      precipitation, average basin temperature, and two land-surface variables,
      offering the potential for synthesis of basin storage time series beyond the
      GRACE observational period. Such an approach could be applied toward gap filling
      between current and future GRACE missions and for predicting basin storage given
      predictions of future precipitation.

PMID- 24563557
TI  - Impact of enhanced-flushing reagents and organic-liquid distribution on mass
      removal and mass-discharge reduction.
AB  - A series of column and flow-cell experiments was conducted to investigate the
      impact of non-uniform organic-liquid distribution on the relationship between
      reductions in contaminant mass discharge and reductions in source zone mass under
      conditions of enhanced-solubilization flushing. Trichloroethene was used as the
      model organic liquid, and SDS (sodium dodecyl sulfate) and ethanol were used as
      representative enhanced-flushing reagents. The results were compared to those of
      water-flood control experiments. Concentrations of trichloroethene in the
      effluent exhibited multi-step behavior with time, wherein multiple secondary
      periods of quasi steady state were observed. This non-ideal behavior was observed
      for both the water-flood and enhanced-flushing experiments. For all flow-cell
      experiments, the later stage of mass removal was controlled by the more poorly-
      accessible mass associated with higher-saturation zones. The profiles relating
      reductions in contaminant mass discharge and reductions in mass exhibited
      generally similar behavior for both the water-flood and enhanced-flushing
      experiments. This indicates that while the rates and magnitudes of mass removal
      are altered by the presence of a solubilization-reagent solution, the fundamental
      mass-removal process is not. The profiles obtained for the flow-cell systems
      differed from those obtained for the column systems, highlighting the impact of
      source-zone heterogeneity on mass-removal behavior.

PMID- 24563559
TI  - WEIGHTED LIKELIHOOD ESTIMATION UNDER TWO-PHASE SAMPLING.
AB  - We develop asymptotic theory for weighted likelihood estimators (WLE) under two
      phase stratified sampling without replacement. We also consider several variants
      of WLEs involving estimated weights and calibration. A set of empirical process
      tools are developed including a Glivenko-Cantelli theorem, a theorem for rates of
      convergence of M-estimators, and a Donsker theorem for the inverse probability
      weighted empirical processes under two-phase sampling and sampling without
      replacement at the second phase. Using these general results, we derive
      asymptotic distributions of the WLE of a finite-dimensional parameter in a
      general semiparametric model where an estimator of a nuisance parameter is
      estimable either at regular or nonregular rates. We illustrate these results and
      methods in the Cox model with right censoring and interval censoring. We compare
      the methods via their asymptotic variances under both sampling without
      replacement and the more usual (and easier to analyze) assumption of Bernoulli
      sampling at the second phase.

PMID- 24563558
TI  - Functional convergence of thalamic and intrinsic projections to cortical layers 4
      and 6.
AB  - Ascending sensory information is conveyed from the thalamus to layers 4 and 6 of
      sensory cortical areas. Interestingly, receptive field properties of cortical
      layer 6 neurons are different from those in layer 4. Do such differences reflect
      distinct inheritance patterns from the thalamus or are they derived instead from
      local cortical circuits? To distinguish between these possibilities, we utilized
      in vitro slice preparations containing the thalamocortical pathways in the
      auditory and somatosensory systems. Responses from neurons in layers 4 and 6 that
      resided in the same column were recorded using whole-cell patch clamp. Laser
      scanning photostimulation via uncaging of glutamate in the thalamus and cortex
      was used to map the functional topography of thalamocortical and intracortical
      inputs to each layer. In addition, we assessed the functional divergence of
      thalamocortical inputs by optical imaging of flavoprotein autofluorescence. We
      found that the thalamocortical inputs to layers 4 and 6 originated from the same
      thalamic domain, but the intracortical projections to the same neurons differed
      dramatically. Our results suggest that the intracortical projections, rather than
      the thalamic inputs, to each layer contribute more to the differences in their
      receptive field properties.

PMID- 24563561
TI  - Partial Molar Volumes of 15-Crown-5 Ether in Mixtures of N,N-Dimethylformamide
      with Water.
AB  - The density of 15-crown-5 ether (15C5) solutions in the mixtures of N,N
      dimethylformamide (DMF) and water (H2O) was measured within the temperature range
      293.15-308.15 K using an Anton Paar oscillatory U-tube densimeter. The results
      were used to calculate the apparent molar volumes (VPhi ) of 15C5 in the mixtures
      of DMF + H2O over the whole concentration range. Using the apparent molar volumes
      and Redlich and Mayer equation, the standard partial molar volumes of 15-crown-5
      were calculated at infinite dilution ([Formula: see text]). The limiting apparent
      molar expansibilities (alpha) were also calculated. The data are discussed from
      the point of view of the effect of concentration changes on interactions in
      solution.

PMID- 24563562
TI  - Shifting Childrearing to Single Mothers: Results from 17 Western Countries.

PMID- 24563563
TI  - Perceived Control is a Transdiagnostic Predictor of Cognitive-Behavior Therapy
      Outcome for Anxiety Disorders.
AB  - Perceived control has been proposed to be a general psychological vulnerability
      factor that confers an elevated risk for developing anxiety disorders, but there
      is limited research examining perceived control during cognitive-behavioral
      therapies (CBT). The present study examined whether treatment resulted in
      improvements in perceived control, and the indirect effects of CBT on changes in
      symptoms of obsessive-compulsive disorder, social phobia, generalized anxiety
      disorder, and panic disorder via changes in perceived control. Participants (n =
      606) were a large clinical sample presenting for treatment at an outpatient
      anxiety disorders clinic. Participants completed a series of self-report
      questionnaires and a structured clinical interview at an intake evaluation and at
      two follow-up assessments 12 and 24 months later, with the majority of
      participants initiating CBT between the first two assessments. Results of latent
      growth curve models indicated that individuals initiating CBT subsequently
      reported large increases in perceived control and significant indirect effects of
      treatment on intraindividual changes in each of the four anxiety disorders
      examined via intraindividual changes in perceived control. These results suggest
      that the promotion of more adaptive perceptions of control is associated with
      recovery from anxiety disorders. Furthermore, the consistent finding of indirect
      effects across the four anxiety disorders examined underscores the
      transdiagnostic importance of perceived control in predicting CBT outcomes.

PMID- 24563564
TI  - Is leisure time availability associated with more or less severe daily stressors?
      An examination using eight-day diary data.
AB  - The stress suppressing model proposes that sufficient resources reduce stress.
      The stress exposure model suggests that certain factors expose individuals to
      more stress. The current study tested these two models by assessing the within
      person lagging effect of leisure time on perceived severity of daily stressors.
      Analyzing eight-day diary data (N=2,022), we found that having more leisure time
      than usual on a day reduced perceived severity of daily stressors the next day
      and that the decrease in severity became larger with further increase in leisure
      time. Additionally, the effect is much stronger among busy individuals who
      usually had little leisure time. The findings demonstrated an accelerated
      suppressing effect that differed between-person, and the lagging effect affords
      stronger implication for causality than correlational analysis.

PMID- 24563560
TI  - Neuroticism and Extraversion in Youth Predict Mental Wellbeing and Life
      Satisfaction 40 Years Later.
AB  - Neuroticism and Extraversion are linked with current wellbeing, but it is unclear
      whether these traits in youth predict wellbeing decades later. We applied
      structural equation modelling to data from 4583 people from the MRC National
      Survey of Health and Development. We examined the effects of Neuroticism and
      Extraversion at ages 16 and 26 years on mental wellbeing and life satisfaction at
      age 60-64 and explored the mediating roles of psychological and physical health.
      Extraversion had direct, positive effects on both measures of wellbeing. The
      impact of Neuroticism on both wellbeing and life satisfaction was largely
      indirect through susceptibility to psychological distress and physical health
      problems. Personality dispositions in youth have enduring influence on wellbeing
      assessed about forty years later.

PMID- 24563566
TI  - Centrifugal Jet Spinning for Highly Efficient and Large-scale Fabrication of
      Barium Titanate Nanofibers.
AB  - The centrifugal jet spinning (CJS) method has been developed to enable large
      scale synthesis of barium titanate nanofibers. Barium titanate nanofibers with
      fiber diameters down to 50 nm and grain sizes around 25 nm were prepared with CJS
      by spinning a sol-gel solution of barium titanate and poly(vinylpyrrolidone) with
      subsequent heat treatment at 850  degrees C. XRD and FTIR analysis demonstrated
      high purity and tetragonal perovskite structured barium titanate nanofibers. SEM
      and TEM images confirm the continuous high aspect ratio structure of barium
      titanate nanofibers after heat treatment. It is demonstrated that the CJS
      technique offers a highly efficient method for large-scale fabrication of ceramic
      nanofibers at production rates of up to 0.3 gram/minute.

PMID- 24563565
TI  - Intelligence indexes generalist genes for cognitive abilities.
AB  - Twin research has supported the concept of intelligence (general cognitive
      ability, g) by showing that genetic correlations between diverse tests of verbal
      and nonverbal cognitive abilities are greater than 0.50. That is, most of the
      genes that affect cognitive abilities are highly pleiotropic in the sense that
      genes that affect one cognitive ability affect all cognitive abilities. The
      impact of this finding may have been blunted because it depends on the validity
      of the twin method. Although the assumptions of the twin method have survived
      indirect tests, it is now possible to test findings from the twin method directly
      using DNA alone in samples of unrelated individuals, without the assumptions of
      the twin method. We applied this DNA method, implemented in a software package
      called Genome-wide Complex Trait Analysis (GCTA), to estimate genetic variance
      and covariance for two verbal tests and two nonverbal tests using 1.7 million DNA
      markers genotyped on 2500 unrelated children at age 12; 1900 children also had
      cognitive data and DNA at age 7. Because each of these individuals is one member
      of a twin pair, we were able to compare GCTA estimates directly to twin study
      estimates using the same measures in the same sample. At age 12, GCTA confirmed
      the results of twin research in showing substantial genetic covariance between
      verbal and nonverbal composites. The GCTA genetic correlation at age 12 was 1.0
      (SE = 0.32), not significantly different from the twin study estimate of 0.60 (SE
      = 0.09). At age 7, the genetic correlations were 0.31 (SE =0.32) from GCTA and
      0.71 (SE = 0.15).from twin analysis. The results from the larger sample and
      stronger measures at age 12 confirm the twin study results that the genetic
      architecture of intelligence is driven by pleiotropic effects on diverse
      cognitive abilities. However, the results at age 7 and the large standard errors
      of GCTA bivariate genetic correlations suggest the need for further research with
      larger samples.

PMID- 24563567
TI  - Toward an Integrated Psycholinguistic, Neurolinguistic, Sensorimotor Framework
      for Speech Production.

PMID- 24563569
TI  - A GENERALIZED FOURIER APPROACH TO ESTIMATING THE NULL PARAMETERS AND PROPORTION
      OF NONNULL EFFECTS IN LARGE-SCALE MULTIPLE TESTING.
AB  - In a recent paper [4], Efron pointed out that an important issue in large-scale
      multiple hypothesis testing is that the null distribution may be unknown and need
      to be estimated. Consider a Gaussian mixture model, where the null distribution
      is known to be normal but both null parameters-the mean and the variance-are
      unknown. We address the problem with a method based on Fourier transformation.
      The Fourier approach was first studied by Jin and Cai [9], which focuses on the
      scenario where any non-null effect has either the same or a larger variance than
      that of the null effects. In this paper, we review the main ideas in [9], and
      propose a generalized Fourier approach to tackle the problem under another
      scenario: any non-null effect has a larger mean than that of the null effects,
      but no constraint is imposed on the variance. This approach and that in [9]
      complement with each other: each approach is successful in a wide class of
      situations where the other fails. Also, we extend the Fourier approach to
      estimate the proportion of non-null effects. The proposed procedures perform well
      both in theory and on simulated data.

PMID- 24563568
TI  - The Aging Neighborhood: Phonological Density in Naming.
AB  - Aging affects the ability to retrieve words for production, despite maintainence
      of lexical knowledge. In this study, we investigate the influence of lexical
      variables on picture naming accuracy and latency in adults ranging in age from 22
      to 86 years. In particular, we explored the influence of phonological
      neighborhood density, which has been shown to exert competitive effects on word
      recognition, but to facilitate word production, a finding with implications for
      models of the lexicon. Naming responses were slower and less accurate for older
      participants, as expected. Target frequency also played a strong role, with
      facilitative frequency effects becoming stronger with age. Neighborhood density
      interacted with age, such that naming was slower for high-density than low
      density items, but only for older subjects. Explaining this finding within an
      interactive activation model suggests that, as we age, the ability of activated
      neighbors to facilitate target production diminishes, while their activation puts
      them in competition with the target.

PMID- 24563570
TI  - Simultaneous bilingual language acquisition: The role of parental input on
      receptive vocabulary development.
AB  - Parents often turn to educators and healthcare professionals for advice on how to
      best support their child's language development. These professionals frequently
      suggest implementing the 'one-parent-one-language' approach to ensure consistent
      exposure to both languages. The goal of this study was to understand how language
      exposure influences the receptive vocabulary development of simultaneous
      bilingual children. To this end, we targeted nine German-French children growing
      up in bilingual families. Their exposure to each language within and outside the
      home was measured, as were their receptive vocabulary abilities in German and
      French. The results indicate that children are receiving imbalanced exposure to
      each language. This imbalance is leading to a slowed development of the receptive
      vocabulary in the minority language, while the majority language is keeping pace
      with monolingual peers. The one-parent-one-language approach does not appear to
      support the development of both of the child's languages in the context described
      in the present study. Bilingual families may need to consider other options for
      supporting the bilingual language development of their children. As
      professionals, we need to provide parents with advice that is based on available
      data and that is flexible with regards to the current and future needs of the
      child and his family.

PMID- 24563571
TI  - A Powerful Test for Multivariate Normality.
AB  - This paper investigates a new test for normality that is easy for biomedical
      researchers to understand and easy to implement in all dimensions. In terms of
      power comparison against a broad range of alternatives, the new test outperforms
      the best known competitors in the literature as demonstrated by simulation
      results. In addition, the proposed test is illustrated using data from real
      biomedical studies.

PMID- 24563572
TI  - Rapid evolution of reduced receptivity to interspecific mating in the dengue
      vector Aedes aegypti in response to satyrization by invasive Aedes albopictus.
AB  - In this paper we examine the effect of reproductive interference on the dynamics
      of two mosquito vectors of public health concern and add to the growing
      literature on the strength and speed with which interspecific reproductive
      interference may drive evolution. Recent evidence supports a role for asymmetric
      reproductive interference, or satyrization, in competitive displacements of Aedes
      aegypti by Aedes albopictus. However, populations of A. aegypti sympatric with A.
      albopictus in nature evolve resistance to satyrization. Here we report that A.
      aegypti from Tucson, Arizona (USA), where A. albopictus are not known to occur,
      are satyrization-susceptible. Furthermore, in cage experiments we demonstrate
      rapid evolution in satyrization-susceptible lines. Exposing allopatric strains of
      A. aegypti to A. albopictus in cages led to significant reductions, within 1-3
      generations, in the frequency of reproductive interference. We also demonstrate
      that satyrization-resistant A. aegypti females derived from selection experiments
      are significantly slower to mate with conspecific males, suggesting a cost for
      the evolution of satyrization-resistance. Results show how interspecific
      interactions between these vector species are rapidly evolving, with implications
      for the arboviral diseases, especially dengue and chikungunya, which they
      transmit.

PMID- 24563574
TI  - Sleep Patterns in Children with Cystic Fibrosis.
AB  - This study examined sleep patterns and the association between sleep and
      perceived health for children with and without CF. Ninety families (45 CF)
      completed questionnaires about the child's sleep and health. Significant group
      differences were found for sleep patterns (bedtime, wake time, total sleep time),
      symptoms of sleep disordered breathing, and sleep disturbances. Poorer perceived
      health was associated with sleep disturbances among children with CF, but not for
      children without CF. This study highlights the importance of including sleep in
      the evaluation of children with CF, as both medical and behavioral interventions
      can improve the sleep of children with CF.

PMID- 24563573
TI  - The Infant EEG Mu Rhythm: Methodological Considerations and Best Practices.
AB  - The EEG mu rhythm, recorded from scalp regions overlying the sensorimotor cortex,
      appears to exhibit mirroring properties: It is reactive when performing an action
      and when observing another perform the same action. Recently, there has been an
      exponential increase in developmental mu rhythm research, partially due to the mu
      rhythm's potential role in our understanding of others' actions as well as a
      variety of other social and cognitive processes (e.g., imitation, theory of mind,
      language). Unfortunately, various methodological issues impede integrating these
      findings into a comprehensive theory of mu rhythm development. The present
      manuscript provides a review of the infant mu rhythm literature while focusing on
      current methodological problems that impede between study comparisons. By
      highlighting these issues and providing an in depth description and analysis we
      aim to heighten awareness and propose guidelines (when possible) that will
      promote rigorous infant mu rhythm research and facilitate between study
      comparisons. This paper is intended as a resource for developmental scientists,
      regardless of EEG expertise.

PMID- 24563575
TI  - Photochemical Reactions of Fluorinated Pyridines at Half-Sandwich Rhodium
      Complexes: Competing Pathways of Reaction.
AB  - Irradiation of CpRh(PMe3)(C2H4) (1; Cp = eta5-C5H5) in the presence of
      pentafluoropyridine in hexane solution at low temperature yields an isolable eta2
      C,C-coordinated pentafluoropyridine complex, CpRh(PMe3)(eta2-C,C-C5NF4) (2). The
      molecular structure of 2 was determined by single-crystal X-ray diffraction,
      showing coordination by C3-C4, unlike previous structures of pentafluoropyridine
      complexes that show N-coordination. Corresponding experiments with 2,3,5,6
      tetrafluoropyridine yield the C-H oxidative addition product CpRh(PMe3)(C5NF4)H
      (3). In contrast, UV irradiation of 1 in hexane, in the presence of 4-substituted
      tetrafluoropyridines C5NF4X, where X = NMe2, OMe, results in elimination of C2H4
      and HF to form the metallacycles CpRh(PMe3)(kappa2-C,C-CH2N(CH3)C5NF3) (4) and
      CpRh(PMe3)(kappa2-C,C-CH2OC5NF3) (5), respectively. The X-ray structure of 4
      shows a planar RhCCNC-five-membered ring. Complexes 2-5 may also be formed by
      thermal reaction of CpRh(PMe3)(Ph)H with the respective pyridines at 50  degrees
      C.

PMID- 24563576
TI  - A new approach to decoupling of bacterial adhesion energies measured by AFM into
      specific and nonspecific components.
AB  - A new method to decoupling of bacterial interactions measured by atomic force
      microscopy (AFM) into specific and nonspecific components is proposed. The new
      method is based on computing the areas under the approach and retraction curves.
      To test the efficacy of the new method, AFM was used to probe the repulsion and
      adhesion energies present between L. monocytogenes cells cultured at five pH
      values (5, 6, 7, 8 and 9) and silicon nitride (Si3N4). Overall adhesion energy
      was then decoupled into its specific and nonspecific components using the new
      method as well as using Poisson statistical approach. Poisson statistical method
      represents the most commonly used approach to decouple bacterial interactions
      into their components. For all pH conditions investigated, specific energies
      dominated the adhesion and a transition in adhesion and repulsion energies for
      cells cultured at pH 7 was observed. When compared, the differences in the
      specific and nonspecific energies obtained using Poisson analysis and the new
      method were on average 2.2% and 6.7%, respectively. The relatively close energies
      obtained using the two approaches demonstrate the efficacy of the new method as
      an alternative way to decouple adhesion energies into their specific and
      nonspecific components.

PMID- 24563577
TI  - Community phylogenetics at the biogeographical scale: cold tolerance, niche
      conservatism and the structure of North American forests.
AB  - AimThe fossil record has led to a historical explanation for forest diversity
      gradients within the cool parts of the Northern Hemisphere, founded on a limited
      ability of woody angiosperm clades to adapt to mid-Tertiary cooling. We tested
      four predictions of how this should be manifested in the phylogenetic structure
      of 91,340 communities: (1) forests to the north should comprise species from
      younger clades (families) than forests to the south; (2) average cold tolerance
      at a local site should be associated with the mean family age (MFA) of species;
      (3) minimum temperature should account for MFA better than alternative
      environmental variables; and (4) traits associated with survival in cold climates
      should evolve under a niche conservatism constraint. LocationThe contiguous
      United States. MethodsWe extracted angiosperms from the US Forest Service's
      Forest Inventory and Analysis database. MFA was calculated by assigning age of
      the family to which each species belongs and averaging across the species in each
      community. We developed a phylogeny to identify phylogenetic signal in five
      traits: realized cold tolerance, seed size, seed dispersal mode, leaf phenology
      and height. Phylogenetic signal representation curves and phylogenetic
      generalized least squares were used to compare patterns of trait evolution
      against Brownian motion. Eleven predictors structured at broad or local scales
      were generated to explore relationships between environment and MFA using random
      forest and general linear models. ResultsConsistent with predictions, (1)
      southern communities comprise angiosperm species from older families than
      northern communities, (2) cold tolerance is the trait most strongly associated
      with local MFA, (3) minimum temperature in the coldest month is the environmental
      variable that best describes MFA, broad-scale variables being much stronger
      correlates than local-scale variables, and (4) the phylogenetic structures of
      cold tolerance and at least one other trait associated with survivorship in cold
      climates indicate niche conservatism. Main conclusionsTropical niche conservatism
      in the face of long-term climate change, probably initiated in the Late
      Cretaceous associated with the rise of the Rocky Mountains, is a strong driver of
      the phylogenetic structure of the angiosperm component of forest communities
      across the USA. However, local deterministic and/or stochastic processes account
      for perhaps a quarter of the variation in the MFA of local communities.

PMID- 24563578
TI  - Profiling Gene Expression in Germinating Brassica Roots.
AB  - Based on previously developed solid-phase gene extraction (SPGE) we examined the
      mRNA profile in primary roots of Brassica rapa seedlings for highly expressed
      genes like ACT7 (actin7), TUB (tubulin1), UBQ (ubiquitin), and low expressed GLK
      (glucokinase) during the first day post-germination. The assessment was based on
      the mRNA load of the SPGE probe of about 2.1 ng. The number of copies of the
      investigated genes changed spatially along the length of primary roots. The
      expression level of all genes differed significantly at each sample position.
      Among the examined genes ACT7 expression was most even along the root. UBQ was
      highest at the tip and root-shoot junction (RS). TUB and GLK showed a basipetal
      gradient. The temporal expression of UBQ was highest in the MZ 9 h after primary
      root emergence and higher than at any other sample position. Expressions of GLK
      in EZ and RS increased gradually over time. SPGE extraction is the result of
      oligo-dT and oligo-dA hybridization and the results illustrate that SPGE can be
      used for gene expression profiling at high spatial and temporal resolution. SPGE
      needles can be used within two weeks when stored at 4  degrees C. Our data
      indicate that gene expression studies that are based on the entire root miss
      important differences in gene expression that SPGE is able to resolve for example
      growth adjustments during gravitropism.

PMID- 24563579
TI  - Computer-Based Learning: Graphical Integration of Whole and Sectional
      Neuroanatomy Improves Long-Term Retention.
AB  - A study was conducted to test the hypothesis that instruction with graphically
      integrated representations of whole and sectional neuroanatomy is especially
      effective for learning to recognize neural structures in sectional imagery (such
      as MRI images). Neuroanatomy was taught to two groups of participants using
      computer graphical models of the human brain. Both groups learned whole anatomy
      first with a three-dimensional model of the brain. One group then learned
      sectional anatomy using two-dimensional sectional representations, with the
      expectation that there would be transfer of learning from whole to sectional
      anatomy. The second group learned sectional anatomy by moving a virtual cutting
      plane through the three-dimensional model. In tests of long-term retention of
      sectional neuroanatomy, the group with graphically integrated representation
      recognized more neural structures that were known to be challenging to learn.
      This study demonstrates the use of graphical representation to facilitate a more
      elaborated (deeper) understanding of complex spatial relations.

PMID- 24563580
TI  - Acoustic location of conspecifics in a nocturnal bird: the corncrake Crex crex.
AB  - Although the use of sounds in spatial orientation is widespread among animals,
      only a few groups advanced such specific adaptations as echolocation. In
      contrast, practically all animals and night-active species in particular, must
      occasionally orient themselves relative to invisible but audible objects such as
      a hidden rival or predator. In this study, I would like to determine the impact
      of locating which involves the use of acoustic parameters of sender's
      vocalisations by receivers and changes of positions and triangulation of sender's
      vocalisations by receivers in estimating the distance to the sender during night
      time territorial interactions of the corncrake (Crex crex). Males were subjected
      to two kinds of stimuli: approaching one, imitating the change of the distance of
      the calling intruder toward the focal male while keeping the direction constant,
      or stationary stimuli, involving acoustic stimulation with no motion. Although
      males subjected to approaching stimulation moved longer distances, in both
      stimuli groups, males moved predominantly toward or out of the playback speaker,
      and only occasionally made sideway movements. However, the results gave no
      evidence of corncrakes moving specifically in order to locate the source of the
      sound; they suggest that males moved toward or away from the already located
      sound. The fact that males moved longer distances in response to approaching than
      stationary stimuli indicates that they were able to perceive the change of the
      distance to the playback speaker based only on structural parameters or amplitude
      of the calls played.

PMID- 24563581
TI  - A Well-Balanced Path-Integral f-Wave Method for Hyperbolic Problems with Source
      Terms.
AB  - Systems of hyperbolic partial differential equations with source terms (balance
      laws) arise in many applications where it is important to compute accurate time
      dependent solutions modeling small perturbations of equilibrium solutions in
      which the source terms balance the hyperbolic part. The f-wave version of the
      wave-propagation algorithm is one approach, but requires the use of a particular
      averaged value of the source terms at each cell interface in order to be "well
      balanced" and exactly maintain steady states. A general approach to choosing this
      average is developed using the theory of path conservative methods. A scalar
      advection equation with a decay or growth term is introduced as a model problem
      for numerical experiments.

PMID- 24563582
TI  - The Role of Dissociation in the Cycle of Violence.
AB  - The primary aim of this study was to examine the role of dissociation in the
      relationship between child maltreatment and intimate partner violence among 148
      inner city women. It was proposed that dissociation would be a mediator in the
      relationship between child maltreatment and intimate partner perpetration.
      Overall, the hypothesis was supported. Findings revealed that women with a
      history of child maltreatment who experienced high levels of dissociation were
      more likely to be perpetrators of intimate partner violence than those with low
      levels of dissociation.

PMID- 24563583
TI  - Long-term follow-up of donor site morbidity after defect coverage with Integra
      following radial forearm flap elevation.
AB  - BACKGROUND: The radial forearm flap (RFF) is known for its excellent and reliable
      results regarding defect coverage though donor site morbidity represents a
      persisting problem. Integra is widely used in reconstructive surgery. This study
      aims to assess long-term outcomes regarding functionality and cosmesis after
      donor site coverage with respect to esthetic appearance, scar quality, and wrist
      function as well as ability to work after donor site coverage with Integra and
      split-thickness skin. METHODS: The prospective follow-up exam, after a mean time
      of 23.8 months, enrolled 13 patients. Identification of patients' comorbidities
      and evaluation of the subjective esthetic outcome, sensibility, cold intolerance,
      and scar instability was assessed by a questionnaire. In clinics, designed Pinch
      test assessed scar tissue mobility over the flexor tendons. The Vancouver Scar
      Scale (VSS) was calculated; wrist function and grip strength were determined.
      RESULTS: The satisfaction score for the esthetic appearance of the donor site was
      in average 3.42 +/- 0.44. Two patients experienced an unstable scar and cold
      intolerance. The VSS resulted in a value of 4.2 representing a good result. The
      pinch test revealed an average scar mobility of 8 mm without any tendon
      adhesions. Active range of motion of the wrist was equal to the non-operated site
      as was grip strength. The pinch test showed a significant negative correlation
      with the VSS making it a reliable tool to measure scar quality. CONCLUSION: Long
      term results show an esthetic and functional successful defect coverage of the
      RFF donor site by the use of Integra and split-thickness skin. Level of Evidence:
      Level IV, therapeutic study.

PMID- 24563584
TI  - Inter-Parent Aggression as a Precursor to Disengagement Coping in Emerging
      Adulthood: The Buffering Role of Friendship Competence.
AB  - Using multi-informant data drawn from a prospective study involving 184 youth,
      mother perpetrated and father perpetrated partner aggression during early
      adolescence (age 13) was examined as a predictor of five types of disengagement
      coping strategies in emerging adulthood (age 21): behavioral disengagement,
      mental disengagement, denial, substance use, and restraint. The ability to
      develop close friendships, or friendship competence, was examined as a moderator
      of these links. Results suggest that inter-parent aggression in early adolescence
      can predict reliance on disengagement coping eight years later, but that
      friendship competence can buffer against the reliance on disengagement coping.
      Moreover, close friendship competence was not directly related to partner
      aggression by mothers or fathers, suggesting that friendship competence develops
      along an independent developmental track, and thus may truly serve as a buffer
      for young adults with a history of exposure to inter-parent aggression.

PMID- 24563586
TI  - Late effect clinic - An integral part of childhood cancer treatment.

PMID- 24563587
TI  - Bedaquiline - The first ATP synthase inhibitor against multi drug resistant
      tuberculosis.
AB  - Increasing incidence of MDR-TB, long duration of treatment and co-infection with
      HIV are the significant problems in achieving the eradication of tuberculosis.
      Bedaquiline is an anti-tuberculosis drug with unique mechanism of action. It
      selectively inhibits the mycobacterial energy metabolism i.e. ATP synthesis and
      found to be effective against all states of Mycobacterium tuberculosis like
      active, dormant, replicating, non-replicating, intracellular and extracellular.
      Preclinical studies have shown the efficacy of bedaquiline in terms of reduction
      in bacterial load and treatment duration. Phase II clinical studies have
      established the safety, tolerability and earlier sputum conversion time in
      patients with MDR-TB. In 2012 FDA approved bedaquiline for treatment of MDR-TB
      and XDR-TB. 

PMID- 24563585
TI  - Role of nitric oxide in developmental biology in plants, bacteria, and man.
AB  - Since its discovery, nitric oxide (NO) has been observed to play an important
      role in the physiology of single-celled organisms as well as high-order
      vertebrates. In this review, we will discuss the involvement of NO in bacterial,
      plant and human systems. NO originates from a variety of sources, namely
      bacterial, plant, and mammalian nitric oxide synthases which oxidize L-arginine.
      Bacterial NO is involved in toxin synthesis, signaling and biofilm formation.
      Organisms use NO to mediate oxidative stress incurred during the innate immune
      response. In plants, large amounts of NO hinder plant growth, while lower
      concentrations regulate normal development. NO and the associated reactive oxygen
      species (ROS) are effective antibacterial, anti-parasitic, and antifungal agents.
      Though NO has therapeutic effects in the immune system, the NO response is
      biphasic and concentration-dependent. NO promotes tumorigenesis within a
      concentration range, and induces apoptosis of cancerous cells at other
      concentrations. The biphasic response to NO is also evident in the regulation of
      chemokine, interleukins, and NF-kappaB, which can promote or inhibit
      inflammation. The physiologic response to NO is concentration dependent. NO, by
      way of non-adrenergic noncholinergic (NANC) nerve transmission, propagates a
      cascade of molecular signaling that facilitates smooth muscle cell relaxation and
      increased arterial inflow into the corpora, initiating an erectile response.
      Additional NO is released through NOS activity in the endothelium in response to
      cholinergic nerve activity and shear stress, which helps to maintain erection.

PMID- 24563588
TI  - Adverse drug reaction and concepts of drug safety in Ayurveda: An overview.
AB  - Drug safety is a very basic and fundamental concept in medical practice. ADRs
      play an important role in assessing patient safety in any system of medicine.
      Pharmacovigilance study is thus significant to understand treatment outcomes.
      Current raised issue with respect to complementary and alternative system
      medicine (CAM) like Ayurveda is increased in number of safety reports along with
      report misinterpretation; this generates the negative impact on system. Although,
      Ayurveda which is holistic system of medicine from India has elaborated the
      causes and methods of drug-induced consequences along with preventive measures
      the available data in classical texts is scattered. The compilation and analysis
      along with modern concept drug safety is need of the hour. Present literature
      review was conducted from various compendium of Ayurveda and electronic data base
      with search terms of 'Vyapad', 'Viruddha', 'Ahita', 'herb-herb interaction',
      'idiosyncrasy', 'Prakritiviruddha' etc. The reported information was analysed for
      the possible correlation on concept of ADR and Pharmacovigilance of current
      science. Overall review demonstrated that drug interaction, iatrogenic, over
      dose, administration of unsuitable drugs, reprehensive drug administration with
      respect to disease, complication from five procedural therapies (Panchakarma) and
      reprehensible preparation of mineral drug are nearer to the modern causes of ADR.
      Thus, concept of drug safety and ADR is not new to the Ayurveda. The concept
      "Drug which is not appropriate to be used as medicine"(Abheshaja) of Ayurveda
      sounds similar as that of modern pharmacovigilance. 

PMID- 24563589
TI  - Molecular characterization and its antioxidant activity of a newly isolated
      Streptomyces coelicoflavus BC 01 from mangrove soil.
AB  - OBJECTIVE: To isolate and identify the biologically active strain of Streptomyces
      species from mangrove soil of Visakhapatnam region. MATERIALS AND METHODS:
      Actinomycetes are isolated by using starch casein agar media and four potential
      strains were selected to evaluate the antioxidant activity by using the standard
      methods DPPH, FRAP and total antioxidant capacity. Further, significant
      antioxidant activity strain characterized by morphological, physiological,
      biochemical and molecular characterization. RESULTS: 20 actinomycetes strains
      were isolated, among them four active isolates designated as BC 01, BC 02, BC 03
      and BC 04 were studied for antioxidant activities. Of these four isolates, BC 01
      showed a potent antioxidant activity when compared with other isolates. The
      morphological, biochemical and molecular characterization of the active isolate
      BC 01 belongs to the genus Streptomyces species. The phylogenetic tree was
      constructed and nucleotide blast in search indicated that the strain is 99.7%
      similarity with Streptomyces coelicoflavus. CONCLUSION: The results of the
      present investigation proven that actinomycetes isolated from mangroves are
      potent source of antioxidants. The strain BC 01 exhibited a potential in vitro
      antioxidant activity; studies of actinomycetes from mangrove soil can be useful
      in discovery of novel species to get novel drugs.

PMID- 24563590
TI  - Simultaneous estimation of degree of crystallinity in combination drug product of
      abacavir, lamivudine and neverapine using X-ray powder diffraction technique.
AB  - OBJECTIVE: In the present study, simultaneous determination of degree of
      crystallinity content in abacavir (ABC), lamivudine (3TC) and neverapine (NVP)
      from there combination drug product using X-ray powder diffraction (XRPD)
      technique is developed and validated. METHODS: The X-ray procedure for the
      identification and determination of the degree of crystallinity in ABC, 3TC and
      NVP drug product is developed and validated. It is based on the X-ray diffraction
      from crystalline region of the drug product. The characteristic peaks of the
      three drugs were characterized using XRPD. RESULTS: ABC, 3TC and NVP
      concentrations ranging from 70% to 130% in drug product were prepared and
      linearity in this concentration range is described. The % coefficient of
      variation (%CV) was found to be 0.9982 for ABC, 0.9978 for 3TC and 0.9984 for
      NVP. The mean recoveries were found to be 100.3% for ABC, 99.0% for 3TC and
      100.8% for NVP. Regressions statistics and Analysis of variance (ANOVA) table
      results were evaluated and found to be satisfactory. CONCLUSIONS: The method has
      been applied to unknown mixtures of drug formulations and stability samples. The
      proposed method can be useful in the quality control of combination drug
      products.

PMID- 24563591
TI  - Development and validation of RP-HPLC method with ultraviolet detection for
      estimation of montelukast in rabbit plasma: Application to preclinical
      pharmacokinetics.
AB  - OBJECTIVE: To develop a liquid-liquid extraction based reverse phase liquid
      chromatography method for estimation of montelukast in rabbit plasma. METHODS:
      Chromatographic separation was carried out using Phenomenex Luna C18 column (250
      mm * 4.6 mm * 5 MUm) with mobile phase composed of ammonium acetate buffer (20
      Mm), pH 5.5 and acetonitrile in 20:80, v/v ratio. The analyte was monitored with
      UV detector at 345 nm. The developed method was validated with respect to
      linearity, accuracy, precision, specificity and stability. RESULTS: The peak area
      ratio of montelukast (MKS) to that of internal standard was used for the
      quantification of samples. Calibration curves were linear in the concentration
      range of 20-2000 ng mL(-1). The LOD and LLOQ of present method were found out to
      be 10 ng mL(-1) and 20 ng mL(-1) respectively. The intra-day and inter-day %CV
      values for MKS were below 6.06% and 8.43%. Intra-day and inter-day accuracies
      were within 95.81% and 110.90%, respectively. Extraction recoveries of drug from
      rabbit plasma were >66.47%. CONCLUSION: A simple, alternative, reproducible and
      sensitive HPLC-UV method was developed for MKS that can be used in preclinical
      pharmacokinetics.

PMID- 24563592
TI  - Evaluation of quality and efficacy of an ethnomedicinal plant Ageratum conyzoides
      L. in the management of pediculosis.
AB  - BACKGROUND: Infestation with the head louse, Pediculus humanus capitis, is one of
      the most common parasitic infestations of human worldwide. Traditionally, the
      main treatment for control of head lice is chemical control that includes wide
      variety of neurotoxic synthetic insecticides. The main difficulty posed in
      controlling the head louse infestation is increasing lice resistance to synthetic
      pediculicidal drugs. Plant-based drugs; especially essential oil components and
      standardized extracts have been suggested as an alternative source of materials
      for insect control. Ageratum conyzoides L. (Asteraceae) has been reported to
      possess antifungal and insecticidal properties. In the present research work, an
      attempt has been made to evaluate in vitro pediculicidal activity of A.
      conyzoides. METHODS: A filter paper diffusion bioassay was carried out in order
      to determine the pediculicidal activity of different extracts of A. conyzoides.
      RESULTS: The study elucidates the active plant part and suitable extract
      responsible for the therapeutic efficacy of this plant in the management of
      pediculosis. CONCLUSION: Findings of the present study indicate the potential of
      A. conyzoides extract to be included in the formulations as a pediculicidal
      agent.

PMID- 24563593
TI  - Prevalence and control of cardiovascular risk factors among type 2 diabetes
      mellitus patients in southern region of Saudi Arabia.
AB  - BACKGROUND/AIM: Dyslipidemia is a significant predictor of cardiovascular events
      and mortality in diabetes patients. The aim of this study is to estimate the
      prevalence rates, characteristics of dyslipidemia and their control in outpatient
      population in a Diabetic Centre. METHODS: A cross sectional prospective study
      design was used to collect data from 255 patients which included patient
      characteristics, past medical history of CVD, medications and parameters related
      to DM and cardiovascular risk factor control. Blood pressure and laboratory
      measurements for glycosylated hemoglobin and lipoprotein panel were recorded.
      RESULTS: Body mass index (BMI) of the dyslipidemic diabetic patients was
      significantly higher for females. In terms of age, duration of diabetes, family
      history, diabetes treatment offered did not differed significantly among genders.
      Clinical characteristics of HDL values were significantly higher for female in
      comparison to men (P = 0.02) whereas glycosylated hemoglobin and blood pressure
      appeared not to differ significantly. Among the three factors studied BMI,
      duration of diabetes mellitus and drug therapy on lipoprotein levels of diabetes
      patients, except for the influence of drug therapy which influenced significantly
      the total cholesterol level (P = 0.02). Number of females with normolipid were
      more than males (P = 0.009) and number of males with abnormal cholesterol and
      triglyceride patients were significantly more than females (0.0002). CONCLUSION:
      Dyslipidemia among males were higher than females which could be a significant
      risk factor for causing low glycemic control culminating in cardiovascular
      events. Control of hyperglycaemia and other CVD risk factor appears to be
      suboptimal in Saudi Arabia. Addressing health system components such as providing
      medical staff training, incentive to health professionals and better patient
      education may improve quality of DM care.

PMID- 24563594
TI  - Efficacy of Cinnamomum cassia Blume. in age induced sexual dysfunction of rats.
AB  - OBJECTIVE: Cinnamomum cassia has been suggested in Ayurveda for the management of
      sexual dysfunction. This research work was conducted to shed some light on the
      mechanism of action of the extract, and evaluate the efficacy of its methanol
      extract in age induced sexual dysfunction in male Wistar rats. Secondary
      objective of the project was to study the effect of treatment on sperm parameters
      and smooth muscle:collagen level in rat penile tissue. METHODS: Young and aged
      male rats were treated with methanol extract of Cinnamomum cassia at a dose of
      100 mg/kg and sexual behavior was observed on 28th day in presence of female rats
      in estrous phase. Sildenafil was used as standard medicine. Effect of treatment
      was studied on epididymal sperm parameters, and Massons trichrome staining of rat
      penile tissues was performed to know the level of smooth muscle:collagen.
      RESULTS: The treatment significantly increased sexual function in aged rats that
      had decreased in comparison to young rats, but did not have any significant
      effect on sperm count, live and defective sperm percentage. However, treatment
      induced an increase in smooth muscle level and a decrease in collagen level in
      the aged rat penile tissue in comparison to that of age matched control.
      CONCLUSION: Based on our studies, we found that Cinnamomum cassia extract was
      effective in management of sexual dysfunction in aged rats and hence we propose a
      possible mechanism of action for Cinnamomum cassia which could be responsible for
      restoring sexual activity in aged rat.

PMID- 24563595
TI  - Synthesis, characterisation and evaluation of N-mannich bases of 2-substituted
      Benzimidazole derivatives.
AB  - RATIONALE: Benzimidazoles and its derivatives represent one of the mainly
      biological active classes of literature. AIM: In this present study aimed to
      synthesize N-mannich bases derivatives compounds bearing of 2-substituted
      benzimidazole moiety, in order to investigate their possible biological activity.
      METHOD: Benzimidazole compounds were prepared from the condensation reaction
      between ortho phenylene diamine and various acids. Mannich base of newly
      synthesized Benzimidazole derivatives were synthesized from 2-substituted
      Benzimidazoles by reacting with secondary amines. The purity of the compounds was
      ascertained by melting point (m.p) and thin layer chromatography (TLC).
      Structures of the synthesized compounds were elucidated by spectral data.
      Antimicrobial assay was performed by microbroth dilution method. Bacterial
      genomic DNA cleavage was assessed by Agarose gel electrophoresis. Toxicity of the
      most effective compounds was studied by Brine-shrimp lethality assay. RESULT:
      Among the synthesized compounds, compound 5E (a) and (b) was establish to be the
      most potent against all tested microorganisms. This two compounds exhibited
      complete bacterial DNA cleavage and non-toxic. CONCLUSION: These results suggest
      that it an interesting compound compared to the current therapeutic agents and
      are considered to investigate further for the same.

PMID- 24563596
TI  - Chitosan-pectin polyelectrolyte complex as a carrier for colon targeted drug
      delivery.
AB  - OBJECTIVE: The objective of present work was to prepare a polyelectrolyte complex
      (PEC) between chitosan (polycation) & pectin (polyanion) and to develop enteric
      coated tablets for colon delivery using the PEC. METHODOLOGY: The PECs were
      prepared using different concentrations of chitosan and pectin. Drug loaded
      enteric coated tablets were prepared by wet granulation method using PEC to
      sustain the release at colon and coating was done with Eudragit S 100 to prevent
      the early release of the drug in stomach and intestine. Two independent variable,
      % PEC (chitosan/pectin) and % coating were optimized by 3(2) full factorial
      design. Statistical model were also used to supplement the optimization. DSC was
      performed to confirm the interaction between the polyions. Developed formulations
      were evaluated for physical appearance, weight variation, thickness, hardness,
      friability, % swelling, assay, in-vitro and ex-vivo drug release studies to
      investigate the PEC's ability to deliver the drug to colon. Ex-vivo release study
      using rat caecal content was also carried out on optimized formulation. RESULTS
      AND DISCUSSION: DSC results confirmed chitosan/pectin interaction and subsequent
      formation of PEC. The optimized formulation containing 1.1% of PEC and 3% of
      coating showed highest swelling and release in alkaline pH mechanism of which was
      found to be microbial enzyme dependent degradation established by ex-vivo study
      using rat caecal content.

PMID- 24563597
TI  - Design and in vitro/in vivo evaluation of extended release matrix tablets of
      nateglinide.
AB  - AIM: Nateglinide is a quick acting anti-diabetic medication whose potent activity
      lasts for a short duration. One of the dangerous side effects of nateglinide
      administration is rapid hypoglycemia, a condition that needs to be monitored
      carefully to prevent unnecessary fatalities. The aim of the study was to develop
      a longer lasting and slower releasing formulation of nateglinide that could be
      administered just once daily. METHODS: Matrix tablets of nateglinide were
      prepared in combination with the polymers hydroxypropylmethylcellulose (HPMC),
      eudragits, ethyl cellulose and polyethylene oxide and the formulated drug release
      patterns were evaluated using in vitro and in vivo studies. CONCLUSION: Of the
      seventeen formulated matrix tablets tested, only one formulation labelled HA-2
      that contained 15% HPMC K4M demonstrated release profile we had aimed for.
      Further, swelling studies and scanning electron microscopic analysis confirmed
      the drug release mechanism of HA-2. The optimized formulation HA-2 was found to
      be stable at accelerated storage conditions for 3 months with respect to drug
      content and physical appearance. Mathematical analysis of the release kinetics of
      HA-2 indicated a coupling of diffusion and erosion mechanisms. In-vitro release
      studies and pharmacokinetic in vivo studies of HA-2 in rabbits confirmed the
      sustained drug release profile we had aimed for.

PMID- 24563598
TI  - In silico QSAR analysis of quercetin reveals its potential as therapeutic drug
      for Alzheimer's disease.
AB  - Acetylcholine-esterase (AchE) inhibitors are one of the most potent drug
      molecules against Alzheimer's disease (AD). But, patients treated with current
      AchE inhibitors often experience severe side effects. Quercetin is a plant
      flavonoid compound which can act as AchE inhibitor and it may be a better
      alternative to current AchE inhibitors in terms of effectiveness with no or fewer
      side effects. AIMS: The aim of the study was to compare quercetin with
      conventional AchE inhibitors to search for a better drug candidate. METHODS AND
      MATERIALS: Physico-chemical properties of conventional drugs and quercetin were
      predicted using bioinformatics tools. Molecular docking of these compounds on the
      active site of AchE was performed using AutoDock and comparative analysis was
      performed. Later, modification on the basic structure of quercetin with different
      functional groups was done to perform QSAR analysis. RESULT AND DISCUSSION:
      Quercetin showed a similar drug likeness score to the conventional drugs. The
      binding strength for quercetin in the active site of the enzyme was -8.8
      kcal/mol, which was considerably higher than binding scores for some of the drugs
      such as donepezil (binding score -7.9 kcal/mol). Fifteen hydrogen bonds were
      predicted between quercetin and the enzyme whereas conventional drugs had fewer
      or even no hydrogen bonds. It implies that quercetin can act as a better
      inhibitor than conventional drugs. To find out even better inhibitor, similar
      structures of quercetin were searched through SIMCOMP database and a methylation
      in the 4-OH position of the molecule showed better binding affinity than parent
      quercetin. Quantitative structure activity relationship study indicated that O-4
      methylation was specifically responsible for better affinity. CONCLUSION: This in
      silico study has conclusively predicted the superiority of the natural compound
      quercetin over the conventional drugs as AchE inhibitor and it sets the need for
      further in-vitro study of this compound in future.

PMID- 24563599
TI  - Design and evaluation of herbal hepatoprotective formulation against paracetamol
      induced liver toxicity.
AB  - AIM: To isolate and identify the quercetin from polyherbal hepatoprotective
      formulation. Polyherbal formulations were developed by using five bioactive
      fractionated extracts of Butea monosperma, Bauhinia variegata and Ocimum
      gratissimum for treatment of liver disorders by exploiting the knowledge of
      traditional system of medicine and evaluated for hepatoprotective activity using
      acute liver toxicity model of paracetamol induced liver damage in rats. METHODS:
      Major active fractions were isolated by solvent fractionation and quantified by
      HPTLC method. Two polyherbal tablet formulations were developed by the wet
      granulation method using microcrystalline cellulose, aerosil and other excipients
      and subjected for physicochemical evaluation to assess physical stability
      followed by pharmacological screening. The prepared tablets were finally
      subjected to stability testing to assess its shelf-life. The rats were monitored
      for change in liver morphology, biochemical parameters like serum glutamate
      pyruvate transaminase (SGPT), serum glutamate oxaloacetate transaminase (SGOT),
      alkaline phosphatase (ALP) and total bilirubin for polyherbal tablet formulation
      at 50 mg/kg and polyherbal tablet formulation at 100 mg/kg. RESULTS: Active
      principle was isolated, quantified by HPTLC and characterized with IR. Both
      formulations showed significant hepatoprotective activity. The histological
      studies were also support the biochemical parameters. From the results of
      biochemical analysis and histopathological studies, it can be accomplished that
      polyherbal tablet formulation at 100 mg/kg can be effectively formulated into a
      suitable dosage form with added benefit of no side effects for control and cure
      of chronic ailments like liver disorders. A comparative histopathological study
      of liver exhibited almost normal architecture as compared to toxicant group.
      CONCLUSION: Biochemical marker showed improved results for polyherbal tablet
      formulation at 100 mg/kg. Polyherbal tablet formulation contains a potent
      hepatoprotective agent suggested to be a flavone concentrated in polyherbal
      formulation which may find clinical application in amelioration of paracetamol
      induced liver damage.

PMID- 24563600
TI  - Herbs in association with drugs: Enhancement of the aminoglycoside-antibiotic
      activity by Pityrogramma calomelanos (L.) Link.
AB  - AIMS: In this work, the ethyl acetate and hexane fractions of Pityrogramma
      calomelanos (L.) were evaluated to antibacterial and antifungal activity against
      strains of Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus,
      Candida albicans, Candida krusei and Candida tropicalis. METHODS: The study was
      performed aiming to assess the antimicrobial effect with the method of dilution
      in HIA. The hexane and ethyl acetate fractions were named HFPC and EAFPC,
      respectively. RESULTS: Both fractions of specie P. calomelanos displayed good
      activity against S. aureus when associated with gentamicin. When associated with
      the antifungal, the fractions did not exhibit relevant activity against species
      of Candida. CONCLUSIONS: These results indicate that this specie can be used as a
      possible source of natural products of antibacterial interest, mainly when
      combined with aminoglycosides.

PMID- 24563601
TI  - Isolation, biochemical and genetic characterizations of alcohol-producing yeasts
      from the flowers of Woodfordia fruticosa.
AB  - OBJECTIVE: To isolate and characterize the alcohol-producing yeasts from
      Woodfordia fruticosa flowers, which are used for the induction and maintenance of
      fermentation in the making of Ayurvedic formulations. MATERIALS AND METHODS:
      Initially twenty four yeasts strains were isolated on MGYP agar plate. Among
      them, four strains were selected for further studies on the basis of their
      alcohol generation capacity using jaggery media (50% w/v). Physiological,
      biochemical and genetic characterization (18S rRNA sequencing) of selected
      strains were carried out. RESULTS: Physiological, biochemical and genetic
      characterization (18S rRNA sequencing) confirmed the strains as Saccharomycopsis
      fibuligera Jm.8, S. fibuligera Jm.10, S. fibuligera Jm.16 and Saccharomyces
      cerevisiae Jm.20. Under the controlled conditions, S. cerevisiae Jm.20 produced
      69.57 g/l of alcohol, whereas remaining strains produced the alcohol in the range
      of 6.04-7.32 g/l. CONCLUSION: Among selected strains, strains S. fibuligera are a
      newer in the flowers. Kinetic study of alcohol generation revealed the strain S.
      cerevisiae Jm.20 can be efficiently used in making of fermented Ayurvedic
      formulations instead of use W. fruticosa flowers.

PMID- 24563602
TI  - Doxycycline induced generalized bullous fixed drug eruption - A case report.
AB  - Adverse drug reactions are a major hazard of modern medicine. Fixed drug
      eruption, which is a cutaneous adverse drug reaction, is commonly seen with
      antimicrobials and analgesics. Here we report 37-year-old female with bullous
      fixed drug eruptions due to doxycycline administration. 

PMID- 24563603
TI  - A CONTROLLED EVALUATION OF A HIGH SCHOOL BIOMEDICAL PIPELINE PROGRAM: DESIGN AND
      METHODS.
AB  - Given limited funding for school-based science education, non-school-based
      programs have been developed at colleges and universities to increase the number
      of students entering science- and health-related careers and address critical
      workforce needs. However, few evaluations of such programs have been conducted.
      We report the design and methods of a controlled trial to evaluate the Stanford
      Medical Youth Science Program's Summer Residential Program (SRP), a 25-year-old
      university-based biomedical pipeline program. This 5-year matched cohort study
      uses an annual survey to assess educational and career outcomes among four
      cohorts of students who participate in the SRP and a matched comparison group of
      applicants who were not chosen to participate in the SRP. Matching on
      sociodemographic and academic background allows control for potential
      confounding. This design enables the testing of whether the SRP has an
      independent effect on educational- and career-related outcomes above and beyond
      the effects of other factors such as gender, ethnicity, socioeconomic background,
      and pre-intervention academic preparation. The results will help determine which
      curriculum components contribute most to successful outcomes and which students
      benefit most. After 4 years of follow-up, the results demonstrate high response
      rates from SRP participants and the comparison group with completion rates near
      90%, similar response rates by gender and ethnicity, and little attrition with
      each additional year of follow-up. This design and methods can potentially be
      replicated to evaluate and improve other biomedical pipeline programs, which are
      increasingly important for equipping more students for science- and health
      related careers.

PMID- 24563604
TI  - Do Sources of Cigarettes Among Adolescents Vary by Age Over Time?
AB  - Trends in sources of cigarettes among adolescents were assessed using data from a
      teen cohort (2000-2006). Five sources-bought from store, got from other teen,
      stole from others, bought from others, and got from an adult-were measured over
      time by age. The most common source among all ages was other teens. Fewer teens
      bought cigarettes from stores, with a downward trend for all ages. Among all ages
      there was an upward trend in stealing with younger teens more likely to steal
      cigarettes. In addition to targeting cigarette sales, interventions are needed to
      target other youth cigarette sources.

PMID- 24563605
TI  - Developing a Multicomponent Model of Nutritious Food Access and Related
      Implications for Community and Policy Practice.
AB  - Access to nutritious foods is limited in disenfranchised communities in the
      United States. Policies are beginning to focus on improving nutritious food
      access in these contexts; yet, few theories are available to guide this work. We
      developed a conceptual model of nutritious food access based on the qualitative
      responses of food consumers in 2 different regions of the American South. Five
      domains (economic, service delivery, spatial-temporal, social, and personal) and
      related dimensions of nutritious food access were identified. The conceptual
      model provides practical guidance to researchers, policy makers, and
      practitioners working to improve nutritious food access in communities.

PMID- 24563607
TI  - Impact of NICU design on environmental noise.
AB  - For neonates requiring intensive care, the optimal sound environment is
      uncertain. Minimal disruptions from medical staff create quieter environments for
      sleep, but limit language exposure necessary for proper language development.
      There are two models of neonatal intensive care units (NICUs): open-bay, in which
      6-to-10 infants are cared for in a single large room; and single-room, in which
      neonates are housed in private, individual hospital rooms. We compared the
      acoustic environments in the two NICU models. We extracted the audio tracks from
      video-electroencephalography (EEG) monitoring studies from neonates in an open
      bay NICU and compared the acoustic environment to that recorded from neonates in
      a new single-room NICU. From each NICU, 18 term infants were studied (total N=36;
      mean gestational age 39.3+/-1.9 weeks). Neither z-scores of the sound level
      variance (0.088+/-0.03 vs. 0.083+/-0.03, p=0.7), nor percent time with peak sound
      variance (above 2 standard deviations; 3.6% vs. 3.8%, p=0.6) were different.
      However, time below 0.05 standard deviations was higher in the single-room NICU
      (76% vs. 70%, p=0.02). We provide objective evidence that single-room NICUs have
      equal sound peaks and overall noise level variability compared with open-bay
      units, but the former may offer significantly more time at lower noise levels.

PMID- 24563608
TI  - Emerging infectious diseases.
AB  - The spectrum of human pathogens and the infectious diseases they cause is
      continuously changing through evolution and changes in the way human populations
      interact with their environment and each other. New human pathogens most often
      emerge from an animal reservoir, emphasizing the central role that non-human
      reservoirs play in human infectious diseases. Pathogens may also re-emerge with
      new characteristics, such as multidrug-resistance, or in different places, such
      as West Nile virus in the USA in 1999, to cause new epidemics. Most human
      pathogens have a history of evolution in which they first emerge and cause
      epidemics, become unstably adapted, re-emerge periodically, and eventually become
      endemic with the potential for future outbreaks.

PMID- 24563606
TI  - Endonuclease and Exonuclease Activities on Oligodeoxynucleotides Containing
      Spiroiminodihydantoin Depend on the Sequence Context and the Lesion
      Stereochemistry.
AB  - 8-Oxo-7,8-dihydro-2'-deoxyguanosine (dOG), a well-studied oxidation product of 2'
      deoxyguanosine (dG), is prone to facile further oxidation forming
      spiroiminodihydantoin 2'-deoxyribonucleoside (dSp) in the nucleotide pool and in
      single-stranded oligodeoxynucleotides (ODNs). Many methods for quantification of
      damaged lesions in the genome rely on digestion of DNA with exonucleases or
      endonucleases and dephosphorylation followed by LC-MS analysis of the resulting
      nucleosides. In this study, enzymatic hydrolysis of dSp-containing ODNs was
      investigated with snake venom phosphodiesterase (SVPD), spleen phosphodiesterase
      (SPD) and nuclease P1. SVPD led to formation of a dinucleotide, 5'-d(Np[Sp])-3'
      (N = any nucleotide) that included the undamaged nucleotide on the 5' side of dSp
      as the final product. This dinucleotide was a substrate for both SPD and nuclease
      P1. A kinetic study of the activity of SPD and nuclease P1 showed a sequence
      dependence on the nucleotide 5' to the lesion with rates in the order
      dG>dA>dT>dC. In addition, the two diastereomers of dSp underwent digestion at
      significantly different rates with dSp1>dSp2; nuclease P1 hydrolyzed the 5'
      d(Np[Sp1])-3' dinucleotide two- to six-fold faster than the corresponding 5'
      d(Np[Sp2])-3', while for SPD the difference was two-fold. These rates are
      chemically reasoned based on dSp diastereomer differences in the syn vs. anti
      glycosidic bond orientation. A method for the complete digestion of dSp
      containing ODNs is also outlined based on treatment with nuclease P1 and SVPD.
      These findings have significant impact on the development of methods to detect
      dSp levels in cellular DNA.

PMID- 24563610
TI  - The role of immigrant enclaves for Latino residential inequalities.
AB  - We investigate the difference that immigrant enclaves make for the residential
      contexts of Latino families in the U.S. We argue that enclaves may no longer
      function simply as temporary way stations, the classic depiction of them, because
      of the compromised legal status of many Latinos. We examine this role with an
      innovative method that uses publicly available census tabulations (from the 2000
      Census in our case) to develop HLM models, in which race/ethnicity and income are
      controlled at the family level, along with neighbourhood context and metropolitan
      characteristics. Comparing Latino residential patterns to those of whites and
      blacks reveals the large neighbourhood disadvantages of Latinos, which except for
      greater exposure to whites are on the order of those suffered by African
      Americans. We find that Hispanic families improve their residential situations as
      their incomes go up and usually also when they live in suburbs. But residence
      outside of immigrant enclaves produces the largest positive changes. The enclaves
      are a fundamentally different kind of residential space, in which the potential
      for neighbourhood improvement is modest.

PMID- 24563609
TI  - Cognitive and Affective Perceptions of Vulnerability as Predictors of Exercise
      Intentions among People with Type 2 Diabetes.
AB  - Most conventional measures of risk perception such as perceived likelihood
      address largely deliberative or cognitive perceptions of vulnerability.
      Nevertheless, affective perceptions of vulnerability such as worry may have
      different antecedents and consequences than do these conventional measures, serve
      as stronger predictors of behavior, and qualify effects of conventional
      deliberative risk perceptions on behavior. In this study, we assessed how worry -
      the most common measure of affective perceptions of vulnerability compared with
      three conventional measures of risk (absolute risk, comparative risk, and
      conditional risk) in predicting behavioral intentions. Participants were 83
      adults with type 2 diabetes who assessed their risk of heart disease and reported
      their intentions to increase physical activity (which reduces heart disease
      risk). As predicted, worry was the only significant predictor of exercise
      intentions such that higher worry was associated with higher intentions.
      Importantly, this relationship was stronger among individuals who perceived their
      absolute risk to be relatively higher and those who perceived their comparative
      risk to be relatively lower, demonstrating that cognitive and affective
      perceptions interact. These findings highlight the importance of not conflating
      affective and cognitive perceptions of vulnerability when assessing perceived
      risk, and suggest the need for more research on how to best conceptualize
      perceived risk in different samples and settings.

PMID- 24563611
TI  - Migrant Values and Beliefs: How Are They Different and How Do They Change?
AB  - This is a study of the values of migrants. We examine processes of selection-how
      values affect migration-and adaptation-how migration influences value changes.
      Empirical analyses use a unique collection of data that combines detailed
      information on values from a representative sample of non-migrants in Nepal with
      a representative sample of Nepali migrants living in the Persian Gulf. Results
      suggest that migrants were selected from those who were more materialistic, less
      committed to religion and more family-oriented. In terms of adaptation, our
      results are consistent with the idea that migrants become more religious, less
      committed to historical Nepali values, and change ideas about family-orientation
      in mixed ways. Thus, we find that value adaptations of migrants are complex
      processes that could have immense impacts on ideational diffusion around the
      world.

PMID- 24563612
TI  - Gravity-induced swirl of nanoparticles in microfluidics.
AB  - Parallel flows of two fluids in microfluidic devices are used for miniaturized
      chemistry, physics, biology and bioengineering studies, and the streams are often
      considered to remain parallel. However, as the two fluids do not always have the
      same density, interface reorientation induced by density stratification is
      unavoidable. In this paper, flow characteristics of an aqueous polystyrene
      nanofluid and a sucrose-densified aqueous solution flowing parallel in
      microchannels are examined. Nanoparticles 100 nm in diameter are used in the
      study. The motion of the nanoparticles is simulated using the Lagrangian
      description and directly observed by a confocal microscope. Matched results are
      obtained from computational and empirical analysis. Although solution density
      homogenizes rapidly resulting from a fast diffusion of sucrose in water, the
      nanofluid is observed to rotate for an extended period. Angular displacement of
      the nanofluid depends on the ratio of gravitational force to viscous force,
      Re/Fr2, where Re is the Reynolds number and Fr is the Froude number. In the
      developing region at the steady state, the angular displacement is related to
      y/Dh, the ratio between distance from the inlet and the hydraulic diameter of the
      microfluidic channel. The development of nanofluid flow feature also depends on
      h/w, the ratio of microfluidic channel's height to width. The quantitative
      description of the angular displacement of nanofluid will aid rational designs of
      microfluidic devices utilizing multistream, multiphase flows.

PMID- 24563613
TI  - Time resolved and temperature dependence of the radiative properties of thiol
      capped CdS nanoparticles films.
AB  - In this work, we present the temperature-dependence and time-resolved
      photoluminescence (PL) of CdS nanoparticles capped independently with three
      different ligands thiophenol, thioglycerol, and l-cysteine over a broad
      temperature range from 10 to 300 K. The respective nanoparticles sizes in the
      three systems studied in this work are 1.5, 4, and 2 nm as determined from X-ray
      diffraction (XRD). From the analysis of AFM images, it was found that the lateral
      particle sizes of capped CdS nanoparticles are greater than those deduced from
      XRD or optical absorption measurements. The aim of this study is the
      investigation of the impact of the organic ligands on the radiative recombination
      dynamics in organically capped CdS nanoparticles. From the PL study and based on
      the temperature-dependence and time-resolved emission spectroscopy, we conclude
      that the emission of CdS QDs film originates from recombination of the
      delocalized carriers in the internal core states with a small contribution of the
      localized carriers at the interface. The PL decay reveals a biexponential
      behavior for the entire three samples at all temperatures. One of the two
      exponential components decays rapidly with a time tau1 in the range 0.5-0.8 ns,
      whereas the other decays much more slowly, with a time tau2 in the range 1-3 ns.
      The weak activation energy (32-37 meV) deduced from the temperature dependence of
      the PL intensity suggests the involvement of shallow traps. The analysis of the
      experimental results reveals a relatively narrow size distribution, an efficient
      surface passivation, and a satisfactory thermal stability of CdS nanocrystals.

PMID- 24563614
TI  - A crossover in Mexican and Mexican-American fertility rates: Evidence and
      explanations for an emerging paradox.
AB  - Against a backdrop of two new developments in the fertility behavior of the
      Mexican-Origin population in the U.S., the present discussion will update
      contemporary Mexican-Origin fertility patterns and address several theoretical
      weaknesses in the current approach to immigrant group fertility. Data come from
      six national surveys (three from Mexico and three from the U.S.) that cover a
      twenty-five year period (1975- 2000). The findings demonstrate dramatic decreases
      in the fertility rates in Mexico at the same time that continuous increases have
      been documented in the fertility rates of native-born Mexican-Americans in the
      U.S. at younger ages. These changes necessitate a reexamination of the idea that
      Mexican pronatalist values are responsible for the high fertility rates found
      within the Mexican-Origin population in the U.S. Instead, they point to the
      increasing relevance of framing the fertility behavior of the Mexican-Origin
      population within a racial stratification perspective that stresses the influence
      of U.S. social context on fertility behavior. As a step in this direction, the
      analysis examines fertility patterns within the Mexican-Origin population in the
      U.S., giving special attention to the role of nativity/generational status in
      contributing to within group differences.

PMID- 24563615
TI  - Multispectral fluorescence ultramicroscopy: three-dimensional visualization and
      automatic quantification of tumor morphology, drug penetration, and
      antiangiogenic treatment response.
AB  - Classic histology still represents the gold standard in tumor tissue analytics.
      However, two-dimensional analysis of single tissue slides does not provide a
      representative overview of the inhomogeneous tumor physiology, and a detailed
      analysis of complex three-dimensional structures is not feasible with this
      technique. To overcome this problem, we applied multispectral fluorescence
      ultramicroscopy (UM) to the field of tumor analysis. Optical sectioning of
      cleared tumor specimen provides the possibility to three-dimensionally acquire
      relevant tumor parameters on a cellular resolution. To analyze the virtual UM
      tumor data sets, we created a novel set of algorithms enabling the fully
      automatic segmentation and quantification of multiple tumor parameters. This new
      postmortem imaging technique was applied to determine the therapeutic treatment
      effect of bevacizumab on the vessel architecture of orthotopic KPL-4 breast
      cancer xenografts at different time points. A significant reduction of the vessel
      volume, number of vessel segments, and branching points in the tumor periphery
      was already detectable 1 day after initiation of treatment. These parameters
      remained virtually unchanged in the center of the tumor. Furthermore, bevacizumab
      induced vessel normalization and reduction in vascular permeability diminished
      the penetration behavior of trastuzumab-Alexa 750 into tumor tissue. Our results
      demonstrated that this newimaging method enables the three-dimensional
      visualization and fully automatic quantification of multiple tumor parameters and
      drug penetration on a cellular level. Therefore,UM is a valuable tool for cancer
      research and drug development. It bridges the gap between common macroscopic and
      microscopic imaging modalities and opens up new three-dimensional (3D) insights
      in tumor biology. 

PMID- 24563616
TI  - SPOP mutations in prostate cancer across demographically diverse patient cohorts.
AB  - BACKGROUND: Recurrent mutations in the Speckle-Type POZ Protein (SPOP) gene occur
      in up to 15% of prostate cancers. However, the frequency and features of cancers
      with these mutations across different populations is unknown. OBJECTIVE: To
      investigate SPOP mutations across diverse cohorts and validate a series of assays
      employing high-resolution melting (HRM) analysis and Sanger sequencing for
      mutational analysis of formalin-fixed paraffin-embedded material. DESIGN SETTING
      AND PARTICIPANTS: 720 prostate cancer samples from six international cohorts
      spanning Caucasian, African American, and Asian patients, including both prostate
      specific antigen-screened and unscreened populations, were screened for their
      SPOP mutation status. Status of SPOP was correlated to molecular features (ERG
      rearrangement, PTEN deletion, and CHD1 deletion) as well as clinical and
      pathologic features. RESULTS AND LIMITATIONS: Overall frequency of SPOP mutations
      was 8.1% (4.6% to 14.4%), SPOP mutation was inversely associated with ERG
      rearrangement (P<.01), and SPOP mutant (SPOPmut) cancers had higher rates of CHD1
      deletions (P<.01). There were no significant differences in biochemical
      recurrence in SPOPmut cancers. Limitations of this study include missing
      mutational data due to sample quality and lack of power to identify a difference
      in clinical outcomes. CONCLUSION: SPOP is mutated in 4.6% to 14.4% of patients
      with prostate cancer across different ethnic and demographic backgrounds. There
      was no significant association between SPOP mutations with ethnicity, clinical,
      or pathologic parameters. Mutual exclusivity of SPOP mutation with ERG
      rearrangement as well as a high association with CHD1 deletion reinforces SPOP
      mutation as defining a distinct molecular subclass of prostate cancer.

PMID- 24563617
TI  - Chromatin redistribution of the DEK oncoprotein represses hTERT transcription in
      leukemias.
AB  - Although numerous factors have been found to modulate hTERT transcription, the
      mechanism of its repression in certain leukemias remains unknown. We show here
      that DEK represses hTERT transcription through its enrichment on the hTERT
      promoter in cells from chronic and acute myeloid leukemias, chronic lymphocytic
      leukemia, but not acute lymphocytic leukemias where hTERT is overexpressed. We
      isolated DEK from the hTERT promoter incubated with nuclear extracts derived from
      fresh acute myelogenous leukemia (AML) cells and from cells expressing Tax, an
      hTERT repressor encoded by the human T cell leukemia virus type 1. In addition to
      the recruitment of DEK, the displacement of two potent known hTERT
      transactivators from the hTERT promoter characterized both AML cells and Tax
      expressing cells. Reporter and chromatin immunoprecipitation assays permitted to
      map the region that supports the repressive effect of DEK on hTERT transcription,
      which was proportionate to the level of DEK-promoter association but not with the
      level of DEK expression. Besides hTERT repression, this context of chromatin
      redistribution of DEK was found to govern about 40% of overall transcriptional
      modifications, including those of cancer-prone genes. In conclusion, DEK emerges
      as an hTERT repressor shared by various leukemia subtypes and seems involved in
      the deregulation of numerous genes associated with leukemogenesis. 

PMID- 24563618
TI  - HLA class II antigen expression in colorectal carcinoma tumors as a favorable
      prognostic marker.
AB  - The goal of this study was to determine the frequency of HLA class II antigen
      expression in colorectal carcinoma (CRC) tumors, its association with the
      clinical course of the disease, and the underlying mechanism(s). Two tissue
      microarrays constructed with 220 and 778 CRC tumors were stained with HLA-DR, DQ,
      and DP antigen-specific monoclonal antibody LGII-612.14, using the
      immunoperoxidase staining technique. The immunohistochemical staining results
      were correlated with the clinical course of the disease. The functional role of
      HLA class II antigens expressed on CRC cells was analyzed by investigating their
      in vitro interactions with immune cells. HLA class II antigens were expressed in
      about 25% of the 220 and 21% of the 778 tumors analyzed with an overall frequency
      of 23%. HLA class II antigens were detected in 19% of colorectal adenomas.
      Importantly, the percentage of stained cells and the staining intensity were
      significantly lower than those detected in CRC tumors. However, HLA class II
      antigen staining was weakly detected only in 5.4% of 37 normal mucosa tissues.
      HLA class II antigen expression was associated with a favorable clinical course
      of the disease. In vitro stimulation with interferon gamma (IFNgamma) induced HLA
      class II antigen expression on two of the four CRC cell lines tested. HLA class
      II antigen expression on CRC cells triggered interleukin-1beta (IL-1beta)
      production by resting monocytes. HLA class II antigen expression in CRC tumors is
      a favorable prognostic marker. This association may reflect stimulation of IL
      1beta production by monocytes. 

PMID- 24563620
TI  - Paradoxically augmented anti-tumorigenic action of proton pump inhibitor and
      GastrininAPCMin/+ intestinal polyposis model.
AB  - Though long-term administration of proton pump inhibitor (PPI) imposed the risk
      of gastrointestinal track tumorigenesis by accompanied hypergastrinemia, no overt
      increases of colon cancer risk were witnessed after a long-term cohort study. Our
      recent investigation revealed that PPI prevented colitis-associated
      carcinogenesis through anti-inflammatory, anti-oxidative, and anti-mutagenic
      mechanisms in spite of hypergastrinemia. Therefore, we hypothesized that PPI
      might either antagonize the trophic action of gastrin on gastrointestinal
      tumorigenesis or synergize to exert augmented anti-tumorigenic actions. We
      challenged APCMin/+ mice with gastrin, PPI, PPI and gastrin together for 10 weeks
      and counted intestinal polyposis accompanied with molecular changes. Gastrin
      significantly increased intestinal polyposis, but combination of PPI and gastrin
      markedly attenuated intestinal polyposis compared to gastrin-promoted APCMin/+
      mice (P<.001), in which significant beta-catenin phosphorylation and inhibition
      of beta-catenin nuclear translocation were observed with PPI alone or combination
      of PPI and gastrin, whereas gastrin treatment significantly increased beta
      catenin nuclear translocation. Significant footprints of apoptosis, G0/G1
      accumulation, inactivation of p38 and extracellular signal-regulated kinase,
      decreased expressions of CD31, and inhibition of tumor necrosis factor-alpha and
      cyclooxygenase-2 were noted in the combination group. In vitro investigations
      were similar to in vivo findings as shown that PPI treatment inhibited the
      binding of gastrin to its receptor, inactivated beta-catenin-associated signaling
      including Tcf/Lef and glycogen synthase kinase beta, and paradoxically inhibited
      beta-catenin-associated proliferative activities. Our investigations explain why
      colon cancer risk has not increased despite long-term use of PPIs and provide a
      rationale for using PPI to achieve anti-tumorigenesis beyond acid suppression.

PMID- 24563619
TI  - Doubling down on the PI3K-AKT-mTOR pathway enhances the antitumor efficacy of
      PARP inhibitor in triple negative breast cancer model beyond BRCA-ness.
AB  - Phosphoinositide 3-kinase (PI3K) pathway, in addition to its pro-proliferative
      and antiapoptotic effects on tumor cells, contributes to DNA damage repair (DDR).
      We hypothesized that GDC-0980, a dual PI3K-mammalian target of rapamycin (mTOR)
      inhibitor, would induce an efficient antitumor effect in BRCA-competent triple
      negative breast cancer (TNBC) model when combined with ABT888 and carboplatin.
      Mechanism-based in vitro studies demonstrated that GDC-0980 treatment alone or in
      combination led to DNA damage (increased pgammaH2AX(S139); Western blot,
      immunofluorescence), gain in poly ADP-ribose (PAR), and a subsequent
      sensitization of BRCA-competent TNBC cells to ABT888 plus carboplatin with a time
      dependent 1) decrease in proliferation signals (pAKTT308/S473, pP70S6KT421/S424,
      pS6RPS235/236), PAR/poly(ADP-ribose) polymerase (PARP) ratios, PAR/pgammaH2AX
      ratios, live/dead cell ratios, cell cycle progression, and three-dimensional
      clonogenic growths and 2) increase in apoptosis markers (cleaved caspases 3 and
      9, a pro-apoptotic BH3-only of Bcl-2 family (BIM), cleaved PARP, annexin V). The
      combination was effective in vitro in BRCA-wild-type PIK3CA-H1047R-mutated BT20
      and PTEN-null HCC70 cells. The combination blocked the growth of established
      xenograft tumors by 80% to 90% with a concomitant decrease in tumor Ki67, CD31,
      phosphorylated vascular endothelial growth factor receptor, pS6RPS235/236, and
      p4EBP1T37/46 as well as an increase in cleaved caspase 3 immunohistochemistry
      (IHC) levels. Interestingly, a combination with GDC-0941, a pan-PI3K inhibitor,
      failed to block the tumor growth in MDA-MB231. Results demonstrate that the dual
      inhibition of PI3K and mTOR regulates DDR. In a BRCA-competent model, GDC-0980
      enhanced the antitumor activity of ABT888 plus carboplatin by inhibiting both
      tumor cell proliferation and tumor-induced angiogenesis along with an increase in
      the tumor cell apoptosis. This is the first mechanism-based study to demonstrate
      the integral role of the PI3K-AKT-mTOR pathway in DDR-mediated antitumor action
      of PARP inhibitor in TNBC.

PMID- 24563621
TI  - Intermittent metronomic drug schedule is essential for activating antitumor
      innate immunity and tumor xenograft regression.
AB  - Metronomic chemotherapy using cyclophosphamide (CPA) is widely associated with
      antiangiogenesis; however, recent studies implicate other immune-based
      mechanisms, including antitumor innate immunity, which can induce major tumor
      regression in implanted brain tumor models. This study demonstrates the critical
      importance of drug schedule: CPA induced a potent antitumor innate immune
      response and tumor regression when administered intermittently on a 6-day
      repeating metronomic schedule but not with the same total exposure to activated
      CPA administered on an every 3-day schedule or using a daily oral regimen that
      serves as the basis for many clinical trials of metronomic chemotherapy. Notably,
      the more frequent metronomic CPA schedules abrogated the antitumor innate immune
      and therapeutic responses. Further, the innate immune response and antitumor
      activity both displayed an unusually steep dose-response curve and were not
      accompanied by antiangiogenesis. The strong recruitment of innate immune cells by
      the 6-day repeating CPA schedule was not sustained, and tumor regression was
      abolished, by a moderate (25%) reduction in CPA dose. Moreover, an ~20% increase
      in CPA dose eliminated the partial tumor regression and weak innate immune cell
      recruitment seen in a subset of the every 6-day treated tumors. Thus, metronomic
      drug treatment must be at a sufficiently high dose but also sufficiently well
      spaced in time to induce strong sustained antitumor immune cell recruitment. Many
      current clinical metronomic chemotherapeutic protocols employ oral daily low-dose
      schedules that do not meet these requirements, suggesting that they may benefit
      from optimization designed to maximize antitumor immune responses. 

PMID- 24563622
TI  - Personalized ovarian cancer disease surveillance and detection of candidate
      therapeutic drug target in circulating tumor DNA.
AB  - Retrospective studies have demonstrated that nearly 50% of patients with ovarian
      cancer with normal cancer antigen 125 (CA125) levels have persistent disease;
      however, prospectively distinguishing between patients is currently impossible.
      Here, we demonstrate that for one patient, with the first reported fibroblast
      growth factor receptor 2 (FGFR2) fusion transcript in ovarian cancer, circulating
      tumor DNA (ctDNA) is a more sensitive and specific biomarker than CA125, and it
      can also inform on a candidate therapeutic. For a 4-year period, during which the
      patient underwent primary debulking surgery and chemotherapy, tumor recurrences,
      and multiple chemotherapeutic regimens, blood samples were longitudinally
      collected and stored. Whereas postsurgical CA125 levels were elevated only three
      times for 28 measurements, the FGFR2 fusion ctDNA biomarker was readily
      detectable by quantitative real-time reverse transcription-polymerase chain
      reaction (PCR) in all of these same blood samples and in the tumor recurrences.
      Given the persistence of the FGFR2 fusion, we treated tumor cells derived from
      this patient and others with the FGFR2 inhibitor BGJ398. Only tumor cells derived
      from this patient were sensitive to FGFR2 inhibitor treatment. Using the same
      methodologic approach, we demonstrate in a second patient with a different fusion
      that PCR and agarose gel electrophoresis can also be used to identify tumor
      specific DNA in the circulation. Taken together, we demonstrate that a relatively
      inexpensive, PCR-based ctDNA surveillance assay can outperform CA125 in
      identifying occult disease. 

PMID- 24563624
TI  - Fixed points of difference operator of meromorphic functions.
AB  - Let f be a transcendental meromorphic function of order less than one. The
      authors prove that the exact difference Deltaf =(z+1)-f(z) has infinitely many
      fixed points, if a ? C and infinity are Borel exceptional values (or Nevanlinna
      deficiency values) of f. These results extend the related results obtained by
      Chen and Shon.

PMID- 24563625
TI  - Partially coherent, radially polarized beam with annular apodization.
AB  - Based on the vectorial Debye theory, the tight focusing properties of partially
      coherent, radially polarized vortex beams are investigated in detail. In this
      paper, we propose to use an amplitude modulated filter in combination with a high
      NA lens to generate long focal depth in the focal region. Numerical results show
      that the generation of long focal depth of FWHM (22.08lambda) is achieved, which
      finds useful application in microscopy techniques such as particle acceleration,
      laser processing, optical micromanipulation, and beam shaping. 

PMID- 24563626
TI  - A cooperative model for IS security risk management in distributed environment.
AB  - Given the increasing cooperation between organizations, the flexible exchange of
      security information across the allied organizations is critical to effectively
      manage information systems (IS) security in a distributed environment. In this
      paper, we develop a cooperative model for IS security risk management in a
      distributed environment. In the proposed model, the exchange of security
      information among the interconnected IS under distributed environment is
      supported by Bayesian networks (BNs). In addition, for an organization's IS, a BN
      is utilized to represent its security environment and dynamically predict its
      security risk level, by which the security manager can select an optimal action
      to safeguard the firm's information resources. The actual case studied
      illustrates the cooperative model presented in this paper and how it can be
      exploited to manage the distributed IS security risk effectively. 

PMID- 24563623
TI  - Mechanisms revealed through general anesthetic photolabeling.
AB  - General anesthetic photolabels are used to reveal molecular targets and molecular
      binding sites of anesthetic ligands. After identification, the relevance of
      anesthetic substrates or binding sites can be tested in biological systems.
      Halothane and photoactive analogs of isoflurane, propofol, etomidate,
      neurosteroids, anthracene, and long chain alcohols have been used in anesthetic
      photolabeling experiments. Interrogated protein targets include the nicotinic
      acetylcholine receptor, GABAA receptor, tubulin, leukocyte function-associated
      antigen-1, and protein kinase C. In this review, we summarize insights revealed
      by photolabeling these targets, as well as general features of anesthetics, such
      as their propensity to partition to mitochondria and bind voltage-dependent anion
      channels. The theory of anesthetic photolabel design and the experimental
      application of photoactive ligands are also discussed.

PMID- 24563627
TI  - In vitro conservation of sweet potato genotypes.
AB  - The aim of this study was to develop a protocol for the in vitro conservation of
      sweet potato genotypes using the slow growth technique. The first experiment was
      conducted in a 4 * 5 * 2 factorial scheme, testing four genotypes (IPB-007, IPB
      052, IPB-072, and IPB-137), five concentrations of abscisic acid (ABA) (0.0, 1.0,
      2.0, 4.0, and 8.0 mg.L-1), and two temperatures (18 and 25 degrees C). The second
      experiment was conducted in a 4 * 3 * 3 factorial scheme at 18 degrees C, testing
      four genotypes (IPB-007, IPB-052, IPB-072, and IPB-137), three variations of MS
      salts (50, 75, and 100%), and three concentrations of sucrose (10, 20, and 30 g.L
      1). Every three months, we evaluated the survival (%), shoot height, and shoot
      viability. In vitro conservation of the sweet potato genotypes IPB-052 and IPB
      007 was obtained over three and six months, respectively, using MS medium plus
      2.0 mg.L-1 of ABA at either 18 or 25 degrees C. Genotypes IPB-072 and IPB-137 can
      be kept for three and six months, respectively, in MS medium without ABA at 18
      degrees C. It is possible to store IPB-052 and IPB-072 for six months and IPB-007
      and IPB-137 for nine months using 30 g.L-1 of sucrose and 50% MS salts.

PMID- 24563629
TI  - On generalization based on bi et Al. Iterative methods with eighth-order
      convergence for solving nonlinear equations.
AB  - The primary goal of this work is to provide a general optimal three-step class of
      iterative methods based on the schemes designed by Bi et al. (2009). Accordingly,
      it requires four functional evaluations per iteration with eighth-order
      convergence. Consequently, it satisfies Kung and Traub's conjecture relevant to
      construction optimal methods without memory. Moreover, some concrete methods of
      this class are shown and implemented numerically, showing their applicability and
      efficiency. 

PMID- 24563628
TI  - Effects of scheduled exercise on cancer-related fatigue in women with early
      breast cancer.
AB  - While physical activity during cancer treatment is found beneficial for breast
      cancer patients, evidence indicates ambiguous findings concerning effects of
      scheduled exercise programs on treatment-related symptoms. This study
      investigated effects of a scheduled home-based exercise intervention in breast
      cancer patients during adjuvant chemotherapy, on cancer-related fatigue, physical
      fitness, and activity level. Sixty-seven women were randomized to an exercise
      intervention group (n = 33, performed strength training 3x/week and 30 minutes
      brisk walking/day) and a control group (n = 34, performed their regular physical
      activity level). Data collection was performed at baseline, at completion of
      chemotherapy (Post1), and 6-month postchemotherapy (Post2). Exercise levels were
      slightly higher in the scheduled exercise group than in the control group. In
      both groups, cancer-related fatigue increased at Post1 but returned to baseline
      at Post2. Physical fitness and activity levels decreased at Post1 but were
      significantly improved at Post2. Significant differences between intervention and
      control groups were not found. The findings suggest that generally recommended
      physical activity levels are enough to relief cancer-related fatigue and restore
      physical capacity in breast cancer patients during adjuvant chemotherapy,
      although one cannot rule out that results reflect diminishing treatment side
      effects over time.

PMID- 24563630
TI  - RRHGE: a novel approach to classify the estrogen receptor based breast cancer
      subtypes.
AB  - BACKGROUND: Breast cancer is the most common type of cancer among females with a
      high mortality rate. It is essential to classify the estrogen receptor based
      breast cancer subtypes into correct subclasses, so that the right treatments can
      be applied to lower the mortality rate. Using gene signatures derived from gene
      interaction networks to classify breast cancers has proven to be more
      reproducible and can achieve higher classification performance. However, the
      interactions in the gene interaction network usually contain many false-positive
      interactions that do not have any biological meanings. Therefore, it is a
      challenge to incorporate the reliability assessment of interactions when deriving
      gene signatures from gene interaction networks. How to effectively extract gene
      signatures from available resources is critical to the success of cancer
      classification. METHODS: We propose a novel method to measure and extract the
      reliable (biologically true or valid) interactions from gene interaction networks
      and incorporate the extracted reliable gene interactions into our proposed RRHGE
      algorithm to identify significant gene signatures from microarray gene expression
      data for classifying ER+ and ER- breast cancer samples. RESULTS: The evaluation
      on real breast cancer samples showed that our RRHGE algorithm achieved higher
      classification accuracy than the existing approaches.

PMID- 24563631
TI  - Current trends in water-in-diesel emulsion as a fuel.
AB  - Water-in-diesel emulsion (WiDE) is an alternative fuel for CI engines that can be
      employed with the existing engine setup with no additional engine retrofitting.
      It has benefits of simultaneous reduction of both NO x and particulate matters in
      addition to its impact in the combustion efficiency improvement, although this
      needs further investigation. This review paper addresses the type of emulsion,
      the microexplosion phenomenon, emulsion stability and physiochemical improvement,
      and effect of water content on the combustion and emissions of WiDE fuel. The
      review also covers the recent experimental methodologies used in the
      investigation of WiDE for both transport and stationary engine applications. In
      this review, the fuel injection pump and spray nozzle arrangement has been found
      to be the most critical components as far as the secondary atomization is
      concerned and further investigation of the effect of these components in the
      microexplosion of the emulsion is suggested to be center of focus. 

PMID- 24563634
TI  - Florida Red Tide Knowledge and Risk Perception: Is there a need for tailored
      messaging?
AB  - Harmful algal blooms of the toxic dinoflagellate, Karenia brevis, occur
      throughout the Gulf of Mexico. Recent research efforts sponsored by the National
      Institute of Environmental Health Sciences (NIEHS) and others found that Florida
      red tide causes both acute and possibly chronic health effects from the toxic
      aerosols. Florida red tide also demonstrated significant social and economic
      impacts to both coastal residents and visitors. In conjunction with the research,
      persistent outreach efforts were conducted over the 11 year period. The goal of
      this project was to assess potential needs for tailored messaging needed among
      different red tide information user groups. Survey participants included 303
      local residents, both with asthma and without, and 'snowbirds (seasonal residents
      that reside in the Sarasota area for more than 3 months but less than 6
      months/year), also both with asthma and without. The questionnaire assessed
      Florida red tide knowledge and risk perception regarding Florida red tide using
      items drawn from two previously published surveys to allow comparison. Our
      results reveal that overall knowledge of Florida red tide has not changed. We
      found that knowledge was consistent across our selected groups and also did not
      vary by age, gender and education level. However, knowledge regarding consumption
      of seafood during Florida red tide has declined. Risk perception increased
      significantly for people who have asthma. Individuals responsible for public
      health communication regarding Florida red tide and human health concerns need to
      continue to pursue more effective outreach messages and delivery methods.

PMID- 24563632
TI  - Hematopoietic and mesenchymal stem cells for the treatment of chronic respiratory
      diseases: role of plasticity and heterogeneity.
AB  - Chronic lung diseases, such as cystic fibrosis (CF), asthma, and chronic
      obstructive pulmonary disease (COPD) are incurable and represent a very high
      social burden. Stem cell-based treatment may represent a hope for the cure of
      these diseases. In this paper, we revise the overall knowledge about the
      plasticity and engraftment of exogenous marrow-derived stem cells into the lung,
      as well as their usefulness in lung repair and therapy of chronic lung diseases.
      The lung is easily accessible and the pathophysiology of these diseases is
      characterized by injury, inflammation, and eventually by remodeling of the
      airways. Bone marrow-derived stem cells, including hematopoietic stem/progenitor
      cells (HSPCs) and mesenchymal stromal (stem) cells (MSCs), encompass a wide array
      of cell subsets with different capacities of engraftment and injured tissue
      regenerating potential. Proof-of-principle that marrow cells administered locally
      may engraft and give rise to specialized epithelial cells has been given, but the
      efficiency of this conversion is too limited to give a therapeutic effect.
      Besides the identification of plasticity mechanisms, the
      characterization/isolation of the stem cell subpopulations represents a major
      challenge to improving the efficacy of transplantation protocols used in
      regenerative medicine for lung diseases. 

PMID- 24563636
TI  - Burn injury: what's in a name? Labels used for burn injury classification: a
      review of the data from 2000-2012.
AB  - Through the years, the burn injury has been described using a variety of labels.
      These labels have ranged from one word terms to phrases including degrees of
      injury or more descriptive terms. A search was conducted relying on a common
      general internet search engine. After multiple searches varying the keywords, the
      top 100 searches identified the most prevalent terms or phrases, ranging from the
      common to the more obscure. The search was repeated using the most prevalent
      terms or phrases identified in the common internet search engine, focusing on
      either the title or abstract for all papers indexed in PubMed. This process
      narrowed the attention to the most common terms or phrases used by the academics
      in their published work. This work therefore focused on measuring the specific
      terms being used today and their frequency of use in the peer reviewed papers
      indexed in the PubMed system. It is difficult to focus on the unique aspects of
      any given profession when there is confusion surrounding a common vocabulary. By
      identifying and noting in the academic literature the most commonly used labels,
      a point of reference can be created for future work. Furthermore, having a common
      and accurate set of labels that are uniformly applied across the profession is
      critical for academia to include in training and education programs for
      physicians, nurses, and paramedical staff. 

PMID- 24563633
TI  - Angiogenesis in spontaneous tumors and implications for comparative tumor
      biology.
AB  - Blood supply is essential for development and growth of tumors and angiogenesis
      is the fundamental process of new blood vessel formation from preexisting ones.
      Angiogenesis is a prognostic indicator for a variety of tumors, and it coincides
      with increased shedding of neoplastic cells into the circulation and metastasis.
      Several molecules such as cell surface receptors, growth factors, and enzymes are
      involved in this process. While antiangiogenic therapy for cancer has been
      proposed over 20 years ago, it has garnered much controversy in recent years
      within the scientific community. The complex relationships between the angiogenic
      signaling cascade and antiangiogenic substances have indicated the angiogenic
      pathway as a valid target for anticancer drug development and VEGF has become the
      primary antiangiogenic drug target. This review discusses the basic and clinical
      perspectives of angiogenesis highlighting the importance of comparative biology
      in understanding tumor angiogenesis and the integration of these model systems
      for future drug development. 

PMID- 24563635
TI  - Liver X Receptor: Crosstalk Node for the Signaling of Lipid Metabolism,
      Carbohydrate Metabolism, and Innate Immunity.
AB  - Liver X Receptor-alpha (LXRalpha, also known as NR1H3) and LXRbeta (NR1H2) are
      members of the nuclear receptor superfamily of ligand-activated transcription
      factors, a superfamily which includes the more widely known glucocorticoid
      receptor, estrogen receptor, thyroid receptor, and peroxisome proliferator
      activated receptors. The LXRs are activated by physiologic sterol ligands (e.g.,
      oxysterols) and by synthetic agonists. In recent years, our understanding of the
      importance of LXRs has expanded across several fields of (patho-)physiology.
      Perhaps best known from a sizeable literature as homeostatic 'cholesterol
      sensors' that drive transcriptional programs promoting cellular cholesterol
      efflux, 'reverse cholesterol transport,' and bile acid synthesis, more recent
      roles for LXRs in glucose homeostasis, atherosclerosis, and innate immunity have
      also been identified. These discoveries complement an emerging literature that
      continues to draw surprisingly intimate connections between host metabolism and
      host defense. The present review will discuss the roles of LXR in the signaling
      of metabolism and innate immunity, and the potential for synthetic LXR agonists
      as novel therapeutics in dyslipidemia, atherosclerosis, disordered glucose
      metabolism, and inflammation.

PMID- 24563637
TI  - High voltage electrical burn injuries in teenage children: case studies with
      similarities (an Indian perspective).
AB  - From 1992 to 2012, a total of 911 paediatric burns were admitted and treated at
      Kanchi Kamakoti Childs Trust Hospital Intensive Burn Care Unit, of these 28
      children had suffered electrical injuries and burns. 7 teenagers suffered high
      voltage electrical burn injuries: 2 were involved in train accidents which caused
      fatal electrical injuries, and 5 had electrical burn injuries caused by similar
      types of accidents, requiring Paediatric Intensive Care Unit (PICU) care,
      repeated surgeries and extensive rehabilitation. A common factor among these
      latter 5 patients was that they were injured by overhead high electrical voltage
      cables. Their management was labour intensive and highly costly. In this report,
      the type of accident, the electrical voltage that produced burns and the
      treatment details are elaborated. Findings included similarities in age and type
      of accident, and failure to implement safety procedures and apply standard norms
      of high voltage transmission feeder lines. 

PMID- 24563638
TI  - Early detection of pneumonia as a risk factor for mortality in burn patients in
      Menoufiya University Hospitals, Egypt.
AB  - Pneumonia is common among critically ill burn patients and is a major cause of
      morbidity and mortality among them. Prediction of mortality in patients with
      severe burns remains unreliable. The aim of this research is to study the
      incidence, early diagnosis and management of nosocomial pneumonia, and to discuss
      the relationship between pneumonia and death in burn patients. This prospective
      study was carried out on 80 burn patients (35 males and 45 females) admitted to
      Menoufiya University Hospital Burn Center and Chest Department, Egypt, from
      September 2011 to March 2012. Our findings showed an overall burn patient
      mortality rate of 26.25 % (21/80), 15% (12/80) incidence of pneumonia, and a 50%
      (6/12) mortality rate among patients with pneumonia compared to 22 % (15/68) for
      those without pneumonia. The incidence of pneumonia was twice as high in the
      subset of patients with inhalation injury as among those without inhalation
      injury (P< 0.001). It was found that the presence of pneumonia, inhalation
      injury, increased burn size, and advanced age were all associated with increased
      mortality (P< 0.001). In the late onset pneumonia, other associated factors also
      contributed to mortality. Severity of disease, severity of illness (APACHE
      score), organ failure, underlying co-morbidities, and VAP PIRO score all have
      significant correlations with mortality rate. Pneumonia was an important factor
      for predicting burn patient mortality. Early detection and management of
      pneumonia are absolutely essential. 

PMID- 24563639
TI  - The properties of the "ideal" donor site dressing: results of a worldwide online
      survey.
AB  - Split skin grafting is a widely used technique for reconstructing skin defects.
      Although a vast number of different coverage options for donor sites have become
      available in daily clinical practice, no optimum dressing material has been found
      to date. For this reason, we conducted a globally-distributed online survey to
      poll for the properties of such an "ideal" donor site dressing, possibly leading
      to an improved clinically-driven direction of future wound dressing developments.
      A total of 69 respondents from 34 countries took part in the questionnaire,
      resulting in a response rate of 13.8% (69/500) over a 1-month period. The
      majority of respondents rated the characteristics of an "ideal" donor site
      dressing to be either "essential" or "desirable" as follows: lack of adhesion to
      the wound bed ("essential": 31/69, 44.9%; "desirable": 30/69, 43.5%); pain-free
      dressing changes ("essential": 38/69, 55.1%; "desirable": 30/69, 43.5%);
      absorbency ("essential": 27/69, 39.1%; "desirable": 33/69, 47.8%); ease of
      removal ("essential": 37/69, 53.6%; "desirable": 27/69, 39.13%). With regard to
      the desired frequency of dressing changes, respondents preferred "no dressing
      change until the donor site has healed" (51/69, 73.9%) in the majority of cases,
      followed by "twice weekly" (10/69, 14.5%), "alternate days" (5/69, 7.2%) and
      "daily" (3/69, 4.3%). With regard to the design of the dressing material, the
      majority of participants preferred a one-piece (composite) dressing product
      (44/69, 63.8%). The majority of respondents also denied the current availability
      of an "ideal" donor site dressing (49/69, 71%). The strength of this study was
      the remarkable geographic distribution of responses; all parts of the world were
      included and participated. We believe that this globally conducted online survey
      has polled for the properties of the "ideal" donor site dressing and possibly
      will lead to an improved clinically-driven direction of future wound dressing
      development. 

PMID- 24563640
TI  - Isn't it time for a cadaver skin bank in South Africa?
AB  - Improvements in comprehensive burn care, as practiced in dedicated burns units,
      have reduced mortality and morbidity rates significantly. Strategies deemed most
      important include the application of fluid resuscitation and nutrition protocols,
      intensive care and antimicrobial dressings, as well as early excision and
      grafting. Autografting is limited, however, by availability in very extensive
      burns, despite the use of expanded (meshed) skin. Alternatives have therefore
      been required, and deceased donor allograft is considered the gold standard.
      Fresh allograft use is limited by supply, and legislative and cultural
      restrictions have significantly influenced availability, despite evidence of its
      efficacy. This necessitates the establishment of a deceased donor skin bank in
      South Africa, with a mandate to procure and store allograft for distribution to
      burns units when required. 

PMID- 24563642
TI  - Open burn wound dressing: a practical option in resource constrained settings.
AB  - Various types of wound care products abound for the treatment of burn injuries.
      Most of these products are rather expensive and beyond the means of many patients
      in poorer countries. This poses a challenge to burn care workers in these
      environments and calls for the adoption of practical solutions with the use of
      less expensive and readily available alternatives. The aim of this study is to
      review the outcome of our burn patients managed with topical silver sulphadiazine
      dressing in terms of time to wound healing and length of hospital stay.
      Consecutive burn patients admitted over a four year period were included in the
      study. The patients were resuscitated along standard protocols and their wounds
      were dressed daily with dermazin. The demographic and clinical characteristics of
      the patients were retrieved and analyzed using the SPSS version 16. The primary
      outcome measure for the study was the time to complete re-epithelialization of
      the wounds and discharge of the patients. 144 patients with a M: F ratio of 2.3:
      1 were managed during the period. The age range was 4 months to 81.9 years with a
      median age of 26 years. The TBSA range was 1 to 99% with a median of 28.5%. The
      mean duration from time of injury to wound healing was 21.5 days with a median of
      17 days. Open burn wound dressing with silver sulphadiazine offers a satisfactory
      outcome and should be considered for burn dressing in low resource settings. 

PMID- 24563643
TI  - Necrotizing soft tissue infections following a scald burn of the lower limb: a
      case report.
AB  - Necrotizing soft tissue infection (NSTI) is a rare but potentially fatal
      infection. It usually complicates skin traumas, such as lacerations, scratches,
      insect bites, burns and recent surgeries. Rapid diagnosis is crucial for a
      favourable prognosis. NSTI is an emergency surgical condition and every delay in
      the operative treatment has a proven negative effect. Recently, a rare case
      presented to us with a late diagnosis of NSTI complicating a scald burn of the
      lower limb. The patient's injury was initially treated as a burn case but
      unfortunately ended in an above knee amputation. We report our management
      experience in this case, with a review of the literature. 

PMID- 24563644
TI  - MBC News.

PMID- 24563641
TI  - Fungal infections in burns: a comprehensive review.
AB  - Burn wound infections remain the most important factor limiting survival in burn
      intensive care units. Large wound surface, impaired immune systems, and broad
      spectrum antibiotic therapy contribute to the growth of opportunistic fungal
      species. Faced with challenging fluid resuscitation, wound excision and
      cardiopulmonary stabilization, mycosis in burns are likely to be underestimated.
      Diagnostic performance can sometimes be delayed because clinical signs are
      unspecific and differentiation between colonization and infection is difficult.
      Therapeutic measures range from infection prophylaxis over treatment with
      antifungal agents towards radical amputation of infected limbs. New methods of
      early and reliable detection of fungal organisms, as well as the use of novel
      antifungal substances, are promising but require wider establishment to confirm
      the beneficial effects in burn patients. This review aims to highlight the main
      important aspects of fungal infections in burns including incidence, infection
      control, diagnostic and therapeutic approaches, prognosis and outcomes. 

PMID- 24563645
TI  - Antiaflatoxigenic activity of Carum copticum essential oil.
AB  - Plants are unique sources of useful metabolites. Plant essential oils display a
      wide range of antimicrobial effects against various pathogens. Here, we studied
      the essential oil from the seeds of Carum copticum. We monitored aflatoxin by
      high-performance liquid chromatography. Results show that Carum copticum
      essential oil inhibits Asergillus parasiticus growth and prevents aflatoxin
      production. The half-maximal inhibitory concentration (IC50) is 127.5 MUg mL-1
      for aflatoxin B1 and 23.22 MUg mL-1 for aflatoxin G1. Our findings show that
      Carum copticum essential oil is a potential candidate for the protection of
      foodstuff and feeds from toxigenic fungus growth and their subsequent aflatoxin
      contamination.

PMID- 24563646
TI  - An agent-based simulation of extirpation of Ceratitis capitata applied to
      invasions in California.
AB  - We present an agent-based simulation (ABS) of Ceratitis capitata ("Medfly")
      developed for estimating the time to extirpation of this pest in areas where
      quarantines and eradication treatments were immediately imposed. We use the ABS,
      implemented in the program MED-FOES, to study seven different outbreaks that
      occurred in Southern California from 2008 to 2010. Results are compared with the
      length of intervention and quarantine imposed by the State, based on a linear
      developmental model (thermal unit accumulation, or "degree-day"). MED-FOES is a
      useful tool for invasive species managers as it incorporates more information
      from the known biology of the Medfly, and includes the important feature of being
      demographically explicit, providing significant improvements over simple degree
      day calculations. While there was general agreement between the length of
      quarantine by degree-day and the time to extirpation indicated by MED-FOES, the
      ABS suggests that the margin of safety varies among cases and that in two cases
      the quarantine may have been excessively long. We also examined changes in the
      number of individuals over time in MED-FOES and conducted a sensitivity analysis
      for one of the outbreaks to explore the role of various input parameters on
      simulation outcomes. While our implementation of the ABS in this work is
      motivated by C. capitata and takes extirpation as a postulate, the simulation is
      very flexible and can be used to study a variety of questions on the invasion
      biology of pest insects and methods proposed to manage or eradicate such species.

PMID- 24563647
TI  - Behavioural responses of Frankliniella occidentalis Pergande larvae to methyl
      jasmonate and cis-jasmone.
AB  - The larval stages of Frankliniella occidentalis Pergande (Thysanoptera:
      Thripidae) cause more direct feeding damage to plants than the adults. We,
      therefore, investigated the behaviour-modifying effects on second instar larvae
      of two jasmonic acid derivatives. The artificial application of methyl jasmonate
      and cis-jasmone, both at 1 % concentration, deterred the larvae from settling in
      a dual choice bean leaf disc assay. We observed a dose-dependent feeding
      deterrence of both jasmonates and calculated the concentration required to reduce
      the feeding damage by 50 % relative to the control treatment (FDC50) for each
      jasmonate. The feeding damage was reduced by the application of cis-jasmone at 1
      % concentration, but not by the jasmonates at the respective FDC50 in no-choice
      leaf disc bioassays. However, significantly more larvae left jasmonate-treated
      whole potted bean plants by migrating to the soil compared with control plants.
      Our results may be exploited extending behavioural manipulation by using plant
      compounds in thrips control programmes to the full lifecycle of the pest. Plant
      compounds could be used in integrated and biological pest management strategies
      against F. occidentalis in combination with the application of various above and
      below ground control measures.

PMID- 24563648
TI  - Are naringenin and quercetin useful chemicals in pest-management strategies?
AB  - The effects of two polyphenolic flavonoids (flavanone naringenin and flavonol
      quercetin) on development, fecundity, and mortality of the pea aphid,
      Acyrthosiphon pisum Harris (Hemiptera: Aphididae), were determined in vitro, on
      an artificial diets. Also determined in vitro (DC EPG method), on sucrose-agarose
      gels, were the effects of flavonoids on the probing and feeding behavior of adult
      apterae. When added to a liquid diet, higher concentrations of studied flavonoids
      increased the developmental time, the pre-reproductive period, and mortality and
      decreased fecundity and the intrinsic rate of natural increase of A. pisum. In
      most events associated with stylet activity (as indicated by EPG waveform g-C),
      differences in probing behavior did not statistically differ between the control
      gel and those with flavonoids; quercetin at 10, 100, and 1,000 ug cm-3 prolonged
      the number of gel penetrations; and quercetin only at 10,000 MUg cm-3 prolonged
      the time the first g-C waveform was observed. Addition of flavonoids to the gels
      generally reduced passive ingestion from fluids of the gels (EPG waveform g-E2).
      At higher concentrations (>1,000 ug cm-3) the flavonoids completely stopped
      salivation (EPG waveform g-E1) and passive ingestion from fluids of the gels (EPG
      waveform g-E2). In events associated with active ingestion (EPG waveform g-G),
      however, differences in feeding behavior did not statistically differ between the
      control gel and those with flavonoids. The present findings demonstrate
      detrimental effects of the flavanone naringenin and flavonol on the behavior of
      the pea aphid. This can be employed in a biotechnological projects for plant
      breeding resistant to herbivores, including aphids.

PMID- 24563649
TI  - Coryneform bacteria in human semen: inter-assay variability in species
      composition detection and biofilm production ability.
AB  - BACKGROUND: Coryneform bacteria constitute an important segment of male
      urogenital microbiota. They have been generally considered as saprophytes,
      although some species have been associated with prostatitis as well. At the same
      time, biofilm infections have been suspected as a cause of prostatitis.
      OBJECTIVE: To identify a set of coryneform bacteria isolated from semen of either
      healthy men or prostatitis patients applying different methods to reveal inter
      assay variability and to determine their ability of adhesion and biofilm
      production. DESIGN: Coryneform bacteria were identified by API Coryne 2.0
      biochemical identification system and 16S rDNA sequencing using different primer
      sets. Quantitative assessment of biofilm production was performed using crystal
      violet binding assay method. RESULTS: The most common species were
      Corynebacterium seminale, C. minutissimum, and Dermabacter hominis. Altogether 14
      species and related genera were found. We observed the best inter-assay agreement
      when identifying C. seminale. Biofilm was observed in 7 out of 24 strains. The
      biofilm-producing strains belonged to Arthrobacter cumminsii, Dermabacter
      hominis, C. minutissimum, and Actinomyces neuii. No differences were found
      between the strains originating from prostatitis patients and healthy men.
      Dermabacter hominis strains were more potent biofilm producers than C. seminale
      strains (p=0.048). CONCLUSIONS: We can conclude that a wide variety of coryneform
      bacteria can be found from the male genital tract, although their exact
      identification is problematic due to insufficient representation in databases.
      Nearly one third of the strains are able to form biofilm that may give them an
      advantage for surviving several host- and treatment-related conditions.

PMID- 24563650
TI  - Single-incision laparoscopic sleeve gastrectomy: initial experience in 20
      patients and 2-year follow-up.
AB  - BACKGROUND: The transumbilical route began being clinically feasible with or
      without unique access devices. SETTING: The setting for this study was a private
      practice at Clinica Las Condes, Santiago, Chile. OBJECTIVE: The objective was to
      describe our experience performing a laparoscopic sleeve gastrectomy (LSG) via
      transumbilical route using a single-port access device in addition to standard
      laparoscopic instruments. METHOD: A prospective nonrandomized protocol was
      applied to patients fulfilling the following inclusion criteria: to have been
      medically indicated for an LSG, to have a body mass index (BMI) of less than or
      equal to 40 kg/m2, and the distance between the xiphoid appendix and umbilicus
      should be less than 22 cm. All patients were female with a median (p50) age of
      34.5 (ranging from 21 to 57) years, a median weight of 92 (ranging from 82.5 to
      113) kg, and a median BMI of 35.1 (ranging from 30.5 to 40) kg/m2. The device
      insertion technique, the gastrectomy, and postoperative management are described.
      RESULTS: LSG via transumbilical route was successfully carried out in 19 of the
      20 patients in whom the procedure was performed; one patient had to be converted
      to a conventional laparoscopic procedure. Mean operating time was 127 (ranging
      from 90 to 170) min. On the second postoperative day, all patients were assessed
      through an upper gastrointestinal barium-contrasted radiological series. There
      was neither morbidity nor mortality in this group. Excess weight loss at 25
      months after surgery was 114 %. CONCLUSIONS: Single-port LSG can be successfully
      performed in selected obese patients with a BMI of less than 40 kg/m2 using
      traditional laparoscopic instruments. The technique allows performing a safe and
      effective vertical gastrectomy.

PMID- 24563651
TI  - The effect of hydroxyapatite nanocrystals on osseointegration of titanium
      implants: an in vivo rabbit study.
AB  - Osseointegration is dependent on implant surface characteristics, including
      surface chemistry and topography. The presence of nanosized calcium phosphates on
      the implant surface is interesting to investigate since they affect both the
      nanotopography and surface chemistry, forming a bone mineral resembling surface.
      In this work, the osseointegration of titanium implants with and without the
      presence of hydroxyapatite (HA) nanocrystals has been evaluated in vivo. The
      integration was examined using removal torque measurements and real-time
      polymerase chain reaction (RT-PCR) analysis. The study was performed using two
      healing time points, 3 and 12 weeks. The results showed that the torque needed to
      remove the implants was insignificant between the non- and HA-coated implants,
      both at weeks 3 and 12. The RT-PCR, however, showed significant differences for
      osteoblast, osteoclast, and proinflammation markers when HA nanocrystals were
      present. 

PMID- 24563652
TI  - Lithium improves survival of PC12 pheochromocytoma cells in high-density cultures
      and after exposure to toxic compounds.
AB  - Autophagy is an evolutionary conserved mechanism that allows for the degradation
      of long-lived proteins and entire organelles which are driven to lysosomes for
      digestion. Different kinds of stressful conditions such as starvation are able to
      induce autophagy. Lithium and rapamycin are potent autophagy inducers with
      different molecular targets. Lithium stimulates autophagy by decreasing the
      intracellular myo-inositol-1,4,5-triphosphate levels, while rapamycin acts
      through the inhibition of the mammalian target of rapamycin (mTOR). The
      correlation between autophagy and cell death is still a matter of debate
      especially in transformed cells. In fact, the execution of autophagy can protect
      cells from death by promptly removing damaged organelles such as mitochondria.
      Nevertheless, an excessive use of the autophagic machinery can drive cells to
      death via a sort of self-cannibalism. Our data show that lithium (used within its
      therapeutic window) stimulates the overgrowth of the rat Pheochromocytoma cell
      line PC12. Besides, lithium and rapamycin protect PC12 cells from toxic compounds
      such as thapsigargin and trimethyltin. Taken together these data indicate that
      pharmacological activation of autophagy allows for the survival of
      Pheochromocytoma cells in stressful conditions such as high-density cultures and
      exposure to toxins. 

PMID- 24563653
TI  - Successful gastric volvulus reduction and gastropexy using a dual endoscope
      technique.
AB  - Gastric volvulus is a life threatening condition characterized by an abnormal
      rotation of the stomach around an axis. Although the first line treatment of this
      disorder is surgical, we report here a case of gastric volvulus that was
      endoscopically managed using a novel strategy. An 83-year-old female with a
      history of pancreatic cancer status postpylorus-preserving Whipple procedure
      presented with a cecal volvulus requiring right hemicolectomy. Postoperative
      imaging included a CT scan and upper GI series that showed a gastric volvulus
      with the antrum located above the diaphragm. An upper endoscopy was advanced
      through the pylorus into the duodenum and left in this position to keep the
      stomach under the diaphragm. A second pediatric endoscope was advanced alongside
      and used to complete percutaneous endoscopic gastrostomy (PEG) placement for
      anterior gastropexy. The patient's volvulus resolved and there were no
      complications. From our review of the literature, the dual endoscopic technique
      employed here has not been previously described. Patients who are poor surgical
      candidates or those who do not require emergent surgery can possibly benefit the
      most from similar minimally invasive endoscopic procedures as described here. 

PMID- 24563654
TI  - Clinical usefulness of oral supplementation with alpha-lipoic Acid, curcumin
      phytosome, and B-group vitamins in patients with carpal tunnel syndrome
      undergoing surgical treatment.
AB  - We investigated the clinical usefulness of oral supplementation with a
      combination product containing alpha-lipoic acid, curcumin phytosome, and B-group
      vitamins in 180 patients with carpal tunnel syndrome (CTS), scheduled to undergo
      surgical decompression of the median nerve. Patients in Group A (n = 60) served
      as controls and did not receive any treatment either before or after surgery.
      Patients in Group B (n = 60) received oral supplementation twice a day for 3
      months both before and after surgery (totaling 6 months of supplementation).
      Patients in Group C (n = 60) received oral supplementation twice a day for 3
      months before surgery only. Patients in Group B showed significantly lower
      nocturnal symptoms scores compared with Group A subjects at both 40 days and 3
      months after surgery (both P values <0.05). Moreover, patients in Group B had a
      significantly lower number of positive Phalen's tests at 3 months compared with
      the other study groups (P < 0.05). We conclude that oral supplementation with
      alpha-lipoic acid, curcumin phytosome, and B-group vitamins twice a day both
      before and after surgery is safe and effective in CTS patients scheduled to
      undergo surgical decompression of the median nerve. 

PMID- 24563655
TI  - Experimental Design for Vector Output Systems.
AB  - We formulate an optimal design problem for the selection of best states to
      observe and optimal sampling times for parameter estimation or inverse problems
      involving complex nonlinear dynamical systems. An iterative algorithm for
      implementation of the resulting methodology is proposed. Its use and efficacy is
      illustrated on two applied problems of practical interest: (i) dynamic models of
      HIV progression and (ii) modeling of the Calvin cycle in plant metabolism and
      growth.

PMID- 24563656
TI  - Child abuse and neglect among orphaned children and youth living in extended
      families in sub-Saharan Africa: What have we learned from qualitative inquiry?
AB  - Researchers and aid organizations have reported that orphans in sub-Saharan
      Africa (SSA) are particularly vulnerable to abuse and neglect. This article is a
      review of qualitative studies that address experiences of maltreatment among
      orphaned children and youth living in extended families in SSA. It aims to inform
      policy and programming by providing a better understanding of the types of
      maltreatment encountered and the perceived risk factors. A literature search was
      carried out using Google, PubMed, Scholars Portal Search and Scopus. Searches of
      relevant bibliographies and publications of authors were also undertaken. Studies
      from peer-reviewed journals and the grey literature were reviewed for relevance
      and quality. Eligible studies had to include orphans living with extended family
      in SSA as participants, explore their maltreatment experiences and employ a sound
      qualitative methodology. Findings were coded, extracted, compared and
      synthesized. Twenty articles, representing 15 studies, were selected. These
      studies, from diverse SSAn countries, reported similar forms of maltreatment
      among orphaned children and youth: experiences of intra-household discrimination;
      material and educational neglect; excessive child labour; exploitation by family
      members and psychological, sexual and physical abuse. The perceived risk factors
      were poverty, living with a non-biological caregiver, stigma and alcohol abuse.
      The findings of the included studies suggest that awareness, prevention and
      intervention initiatives aimed to curb child abuse and neglect within communities
      in SSA are needed and should be coupled with efforts to promote education and
      reduce poverty and stigma.

PMID- 24563657
TI  - When Life is a Drag: Depressive Symptoms Associated with Early Adolescent
      Smoking.
AB  - Adolescent nicotine use continues to be a significant public health problem. We
      examined the relationship between the age of youth reporting current smoking and
      concurrent risk and protective factors in a large state-wide sample. We analyzed
      current smoking, depressive symptoms, and socio-demographic factors among 4,027
      adolescents, ages 12-17 years using multivariate logistic regression (see 2005
      California Health Interview Survey (CHIS) Public Use File). Consistent with
      previous work, Latinos, girls, those whose family incomes were below the poverty
      level, and those with fair-poor health were more likely to display depressive
      symptoms. Males, whites, older teens and those in fair-poor health were more
      likely to be current smokers. In a multivariate analysis predicting depressive
      symptoms, the interaction between age and current smoking was highly significant
      (Wald Chi2=15.8, p<.01). At ages 12-14 years, the probability of depressive
      symptoms was estimated to be four times greater among adolescents who currently
      smoked, compared to those who were not current smokers. The likelihood of
      depressive symptoms associated with current smoking decreases with age and
      becomes non-significant by 17 years. Interventions to reduce smoking may be most
      useful among youth prior to age 12 years and must be targeted at multiple risks
      (e.g. smoking and depression).

PMID- 24563658
TI  - Synergistic combinations of favipiravir and oseltamivir against wild-type
      pandemic and oseltamivir-resistant influenza A virus infections in mice.
AB  - AIM: Favipiravir and oseltamivir are antiviral compounds used for the treatment
      of influenza infections. We have aimed to investigate the efficacy of the
      compounds in combination to treat influenza H1N1 virus infections in mice.
      MATERIALS & METHODS: Mice infected with pandemic influenza A/California/04/2009
      (H1N1pdm) virus or an oseltamivir-resistant (H275Y neuraminidase mutation)
      influenza A/Mississippi/ 3/2001 (H1N1) virus were treated orally with inhibitors
      twice a day for 5 days starting 4 h after infection. RESULTS: Complete protection
      from death was afforded by favipiravir treatments of 100 mg/kg/day, but lower
      doses were less effective. Combinations of oseltamivir (1 and 3 mg/kg/day) with
      favipiravir (3, 10 and 30 mg/kg/day) resulted in a synergistic improvement in
      survival rates against H1N1pdm infections. Significant reductions in lung virus
      titers also occurred. Against the H275Y virus infection, oseltamivir alone was
      only 30% protective from death at 100 mg/kg/day, but combinations of the two
      compounds produced a synergistic improvement in survival rate. CONCLUSION: The
      utility of treating H1N1 influenza virus infections with oseltamivir and
      favipiravir in combination has been established.

PMID- 24563659
TI  - Orthopoxvirus inhibitors that are active in animal models: an update from 2008 to
      2012.
AB  - Antiviral agents are being sought as countermeasures for the potential deliberate
      release of smallpox (variola) and monkeypox viruses, for the treatment of
      naturally acquired monkeypox virus infections, and as therapy for complications
      due to smallpox (live-attenuated vaccinia virus) vaccination or accidental
      infection after exposure to vaccinated persons. Reviews of the scientific
      literature spanning 1950-2008 have documented the progress made in developing
      small-animal models of poxvirus infection and identifying novel antiviral agents.
      Compounds of considerable interest include cidofovir, CMX001 and ST-246(r)
      (tecovirimat; SIGA Technologies, NY, USA). New inhibitors have been identified
      since 2008, most of which do not exhibit the kind of potency and selectivity
      required for drug development. Two promising agents include 4'-thioidoxuridine (a
      nucleoside analog) and mDEF201 (an adenovirus-vectored interferon). Compounds
      that have been effectively used in combination studies include vaccinia immune
      globulin, cidofovir, ST-246 and CMX001. In the future there may be an increase in
      experimental work using active compounds in combination.

PMID- 24563661
TI  - Naturalising Representational Content.
AB  - This paper sets out a view about the explanatory role of representational content
      and advocates one approach to naturalising content - to giving a naturalistic
      account of what makes an entity a representation and in virtue of what it has the
      content it does. It argues for pluralism about the metaphysics of content and
      suggests that a good strategy is to ask the content question with respect to a
      variety of predictively successful information processing models in experimental
      psychology and cognitive neuroscience; and hence that data from psychology and
      cognitive neuroscience should play a greater role in theorising about the nature
      of content. Finally, the contours of the view are illustrated by drawing out and
      defending a surprising consequence: that individuation of vehicles of content is
      partly externalist.

PMID- 24563663
TI  - Rethinking "Patient Testimony" in the Medical Humanities: The Case of
      Schizophrenia Bulletin's First Person Accounts.

PMID- 24563662
TI  - Intact Hedonic Responses to Sweet Tastes in Autism Spectrum Disorder.
AB  - The Sweet Taste Test (STT) is a standardized measure designed to index the
      ability to detect differences in sweet tastes (sweet taste sensitivity) and
      hedonic responses to sweet tastes (sweet taste liking). Profiles of response on
      the STT suggest enhanced hedonic responses to sweet tastes in psychiatric
      disorders characterized by dysfunctional reward processing systems, including
      binge-eating disorders and substance use disorders, and a putative mechanism
      governing STT responses is the brain opioid system. The present study examined
      STT responses in 20 adults with autism spectrum disorder (ASD) and 38 healthy
      control adults. There were no differences in sweet taste sensitivity or hedonic
      response to sweet tastes between the ASD and control groups. Within the ASD
      sample, ASD symptom severity was associated with sweet taste sensitivity, but not
      hedonic response to sweet taste. Results may ultimately shed light on brain
      opioid system functioning in ASD.

PMID- 24563664
TI  - The Healthy for Life Taekwondo Pilot Study: A Preliminary Evaluation of Effects
      on Executive Function and BMI, Feasibility, and Acceptability.
AB  - There is growing consensus that exercise improves cognitive functioning, but
      research is needed to identify exercise interventions that optimize effects on
      cognition. The objective of this pilot study was to evaluate Taekwondo
      implemented in public middle school physical education (PE). Two classes were
      randomly assigned to either: five sessions per week of PE or three sessions of PE
      and two sessions of Taekwondo. In PE sessions, evidence-based curriculum to
      address the Presidential Core Fitness Guidelines and California Physical Fitness
      Tests was implemented. Taekwondo sessions included traditional techniques and
      forms taught in an environment emphasizing respect and self-control. Sixty
      students were evaluated at baseline and during the last week of the intervention
      (nine months later). Differences in mean residualized change scores for parent
      rated inhibitory behavioral control yielded a significant, large effect size (d
      =.95, p =.00), reflecting greater improvement among Taekwondo students. Results
      from an executive function computer-administered task revealed greater accuracy
      on the congruent trial (d = 2.00, p = .02) for Taekwondo students. Differences in
      mean residualized change scores for BMI z scores yielded a moderate, non
      significant effect size (d = - .51, p = .16). The majority of Taekwondo students
      reported positive perceptions of Taekwondo and perceived self-improvement in self
      control and physical fitness. Results suggest that Taekwondo is an exercise
      program that improves cognitive functioning and is both feasible and acceptable
      to implement in a public school setting.

PMID- 24563665
TI  - Density functional theory in materials science.
AB  - Materials science is a highly interdisciplinary field. It is devoted to the
      understanding of the relationship between (a) fundamental physical and chemical
      properties governing processes at the atomistic scale with (b) typically
      macroscopic properties required of materials in engineering applications. For
      many materials, this relationship is not only determined by chemical composition,
      but strongly governed by microstructure. The latter is a consequence of carefully
      selected process conditions (e.g., mechanical forming and annealing in metallurgy
      or epitaxial growth in semiconductor technology). A key task of computational
      materials science is to unravel the often hidden composition-structure-property
      relationships using computational techniques. The present paper does not aim to
      give a complete review of all aspects of materials science. Rather, we will
      present the key concepts underlying the computation of selected material
      properties and discuss the major classes of materials to which they are applied.
      Specifically, our focus will be on methods used to describe single or
      polycrystalline bulk materials of semiconductor, metal or ceramic form.

PMID- 24563660
TI  - Roles of Eicosanoids in Prostate Cancer.
AB  - Eicosanoids, the metabolites of arachidonic acid, have diverse functions in the
      regulation of cancer including prostate cancer. This review will provide an
      overview of the roles of eicosanoids and endocannabinoids and their potential as
      therapeutic targets for prostate cancer treatment.

PMID- 24563666
TI  - The invasive assessment of coronary atherosclerosis and stents using optical
      coherence tomography: a clinical update.
AB  - Ischaemic heart disease (IHD) remains one of the leading causes of death.
      Atherosclerosis has been intensely researched given the IHD prevalence and the
      financial impacts on healthcare systems. More recently, in vivo characterisation
      of coronary atherosclerotic plaque and tissue responses following stent
      implantation in a coronary artery has been made possible by a novel technology
      called optical coherence tomography (OCT). OCT is a light-based, invasive,
      intracoronary imaging modality long applied to the field of ophthalmology and now
      in clinical use worldwide. It gives a unique view of within the coronary artery
      using near-infrared light with a resolution of 15 microns, 10 times higher than
      other invasive coronary imaging techniques like intravascular ultrasound. The
      technology is being adopted to comprehensively detect features that make plaques
      'vulnerable' (eg, large lipid pool, thin, fibrous-cap atheroma), whether stents
      are implanted optimally within the artery, and visualise the small layers of
      tissue that form over stent metal surfaces over time, which in turn may provide
      surrogate markers for long-term stent safety and help guide the optimal duration
      of dual antiplatelet therapy, a topic of big discussion at the current point of
      time.

PMID- 24563667
TI  - Receipt of Angiotensin-Converting Enzyme Inhibitors or Angiotensin II Receptor
      Blockers among Medicare Beneficiaries with Diabetes and Hypertension.
AB  - OBJECTIVES: The proportion of patients with diabetes and hypertension receiving
      angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers
      (ACE/ARB), is one of the quality measures for medication management employed by
      the Centers for Medicare and Medicaid Services to rate Medicare Part D plans. The
      objectives of this study were to determine the rate and predictors of receiving
      ACE/ARB in physician office and outpatient visits made by Medicare beneficiaries
      with diabetes and hypertension. METHODS: The study population was Medicare
      beneficiaries with diabetes and hypertension from the National Ambulatory Medical
      Care Survey and National Hospital Ambulatory Medical Care Survey Outpatient
      Department, from 2007 to 2009. Predictors of receiving ACE/ARB were determined
      using bivariate and multivariate logistic regression analysis. KEY FINDINGS: Of
      the 6,311 Medicare outpatient and physician office visits with hypertension and
      diabetes, 40.70% patient visits were associated with receiving ACE/ARB. Bivariate
      analysis found that higher proportions of ACE/ARB were received during visits
      made to primary care physicians compared to visits to non-primary care physicians
      (48.39% vs. 32.56%; p<0.05). Adjusted multivariate analyses indicated that
      ACE/ARB were more likely to be received during visits to primary care physicians
      than visits to non-primary care physicians (odds ratio [OR]: 1.96; 95% confidence
      interval [CI]: 1.59-2.43), and ACE/ARB were more likely to be received during
      visits by patients residing in zip codes with median household income within
      Quartile 2 ($32,794-$40,626), compared to visits by patients residing in zip
      codes with median household income within Quartile 1 (< $32,793, OR: 1.45; 95%
      CI: 1.13-1.87). CONCLUSIONS: Fewer than half of the patient visits were
      associated with receiving ACE/ARB. Promoting evidence-based medicine and
      increasing access to primary care may have the potential to increase the rates of
      receiving ACE/ARB in this population.

PMID- 24563668
TI  - Evaluation of antioxidant and antiangiogenic properties of caesalpinia echinata
      extracts.
AB  - Natural products contain important combinations of ingredients, which may to some
      extent help to modulate the effects produced by oxidation substrates in
      biological systems. It is known that substances capable of modulating the action
      of these oxidants on tissue may be important allies in the control of
      neovascularization in pathological processes. The aim of this study was to
      evaluate the antioxidant and antiangiogenic properties of an ethanol extract of
      Caesalpinia echinata. The evaluation of antioxidant properties was tested using
      two methods (DPPH inhibition and sequestration of nitric oxide). The
      antiangiogenic properties were evaluated using the inflammatory angiogenesis
      model in the corneas of rats. The extract of C. echinata demonstrated a high
      capacity to inhibit free radicals, with IC50 equal to 42.404 ug/mL for the DPPH
      test and 234.2 ug/mL for nitric oxide. Moreover, it showed itself capable of
      inhibiting the inflammatory angiogenic response by 77.49%. These data suggest
      that biochemical components belonging to the extract of C. echinata interfere in
      mechanisms that control the angiogenic process, mediated by substrates belonging
      to the arachidonic acid cascade, although the data described above also suggest
      that the NO buffer may contribute to some extent to the reduction in the
      angiogenic response. 

PMID- 24563669
TI  - Endometrial cancer incidence in breast cancer patients correlating with age and
      duration of tamoxifen use: a population based study.
AB  - BACKGROUND: Our study aimed to assess the endometrial cancer risk after tamoxifen
      adjuvant treatment for female breast cancer patients in Taiwan. MATERIALS AND
      METHODS: A total of 74,280 breast cancer patients between January 1997 and
      December 2004 were included in the study; 39,411 received tamoxifen treatment and
      34,869 did not. Tamoxifen-associated endometrial cancer was defined as
      endometrial cancer that occurred in patients at least 6-month after the diagnosis
      of breast cancer, who underwent tamoxifen treatment. RESULTS: A total of 222
      patients developed endometrial cancer, and of these,153 (69 %) were seen in
      patients with tamoxifen treatment, and 69 (31%) were seen in patients without the
      use of tamoxifen. The incidence of endometrial cancer was 0.388% (153/39,411) in
      patients with tamoxifen treatment, while was 0.198% (69/34,869) in patients
      without tamoxifen treatment. Logistic regression analysis demonstrated that
      tamoxifen use and age over 35 years were significantly correlated with
      development of endometrial cancer (p<0.001 and p=0.002, respectively). The odds
      ratio was 2.94 (95%CI, 2.13-4.06) for 3 years or longer tamoxifen use. The odds
      ratio was 4.08 (95%CI, 1.67-9.93) for women older than 35 years compared to those
      35 or younger than 35 years. There were no significant differences in prior
      hormone exposure, hypertension and diabetes. CONCLUSIONS: To the best of our
      knowledge, this is the largest population based study that shows in patients with
      breast cancer, tamoxifen use for more than three years or patients older than 35
      years was associated with a significantly increased risk for developing
      endometrial cancer.

PMID- 24563670
TI  - A Majority of Low (1-10%) ER Positive Breast Cancers Behave Like Hormone Receptor
      Negative Tumors.
AB  - BACKGROUND: The 2010 guidelines by ASCO-CAP have mandated that breast cancer
      specimens with >=1% positively staining cells by immunohistochemistry should be
      considered Estrogen Receptor (ER) positive. This has led to a subclass of low-ER
      positive (1-10%) breast cancers. We have examined the biology and clinical
      behavior of these low ER staining tumors. METHODS: We have developed a
      probabilistic score of the "ER-positivity" by quantitative estimation of ER
      related gene transcripts from FFPE specimens. Immunohistochemistry for ER was
      done on 240 surgically excised tumors of primary breast cancer. Relative
      transcript abundance of 3 house-keeping genes and 6 ER related genes were
      determined by q-RT PCR. A logistic regression model using 3 ER associated genes
      provided the best probability function, and a cut-off value was derived by ROC
      analysis. 144 high ER (>10%), 75 ER negative and 21 low-ER (1-10%) tumors were
      evaluated using the probability score and the disease specific survival was
      compared. RESULTS: Half of the low-ER positive tumors were assigned to the ER
      negative group based on the probability score; in contrast 95% of ER negative and
      92% of the high ER positive tumors were assigned to the appropriate ER group
      (p<0.0001). The survival of the low-ER group was intermediate between that of the
      high ER positive and ER negative groups (p<0.05). CONCLUSION: Our results suggest
      that the newly lowered ASCO-CAP criteria for ER positivity, leads to the false
      categorization of biologically ER negative tumors as ER positive ones. This may
      have particular relevance to India, where we have a much higher proportion of ER
      negative tumors in general.

PMID- 24563671
TI  - PD-L1 Expression in Clear Cell Renal Cell Carcinoma: An Analysis of Nephrectomy
      and Sites of Metastases.
AB  - BACKGROUND: Expression of programmed death ligand (PD-L1/B7-H1/CD274) represents
      a mechanism of immune escape for renal cell carcinoma (RCC) cells. Drugs blocking
      PD-L1 or its receptor are in clinical development and early data suggests that
      tumor PD-L1 expression may predict response. PATIENTS AND METHODS: A tissue
      microarray (TMA) consisting of four biopsy cores from 34 matched pairs of
      nephrectomy and metastatic sites of clear cell RCC was used to assess PD-L1
      expression by quantitative immunofluorescence. Assessment of intra- and inter
      tumor heterogeneity and primary and metastatic tumor expression was performed
      using a method of Automated Quantitative Analysis (AQUA). RESULTS: The median
      AQUA scores were higher in metastatic than primary specimens (P < 0.0001). The
      correlation between PD-L1 expression in matched primary and metastatic specimens
      was weak (R= 0.24). Within a given tumor, variable PD-L1 staining heterogeneity
      was seen, however the degree of heterogeneity was similar in primary and
      metastatic sites (P = 0.482). CONCLUSIONS: The weak correlation between PD-L1
      expression in primary and metastatic sites for a given patient suggests that
      expression in nephrectomy specimens cannot be used to select metastatic RCC
      patients for PD-L1 and PD-1 inhibitors. The intra-tumor heterogeneity seen in
      both primary and metastatic specimens indicates that a single core biopsy might
      not be sufficient to determine PD-L1 expression.

PMID- 24563672
TI  - Combination of Diane-35 and Metformin to Treat Early Endometrial Carcinoma in
      PCOS Women with Insulin Resistance.
AB  - BACKGROUND: Young women with polycystic ovary syndrome (PCOS) have a high risk of
      developing endometrial carcinoma. There is a need for the development of new
      medical therapies that can reduce the need for surgical intervention so as to
      preserve the fertility of these patients. The aim of the study was to describe
      and discuss cases of PCOS and insulin resistance (IR) women with early
      endometrial carcinoma while being co-treated with Diane-35 and metformin.
      METHODS: Five PCOS-IR women who were scheduled for diagnosis and therapy for
      early endometrial carcinoma were recruited. The hospital records and endometrial
      pathology reports were reviewed. All patients were co-treated with Diane-35 and
      metformin for 6 months to reverse the endometrial carcinoma and preserve their
      fertility. Before, during, and after treatment, endometrial biopsies and blood
      samples were obtained and oral glucose tolerance tests were performed.
      Endometrial pathology was evaluated. Body weight (BW), body mass index (BMI),
      follicle-stimulating hormone (FSH), luteinizing hormone (LH), total testosterone
      (TT), sex hormone-binding globulin (SHBG), free androgen index (FAI), insulin
      area under curve (IAUC), and homeostasis model assessment of insulin resistance
      (HOMA-IR) were determined. RESULTS: Clinical stage 1a, low grade endometrial
      carcinoma was confirmed before treatment. After 6 months of co-treatment, all
      patients showed normal epithelia. No evidence of atypical hyperplasia or
      endometrial carcinoma was found. Co-treatment resulted in significant decreases
      in BW, BMI, TT, FAI, IAUC, and HOMA-IR in parallel with a significant increase in
      SHBG. There were no differences in the FSH and LH levels after co-treatment.
      CONCLUSIONS: Combined treatment with Diane-35 and metformin has the potential to
      revert the endometrial carcinoma into normal endometrial cells in PCOS-IR women.
      The cellular and molecular mechanisms behind this effect merit further
      investigation.

PMID- 24563673
TI  - Potential Urinary miRNA Biomarker Candidates for the Accurate Detection of
      Prostate Cancer among Benign Prostatic Hyperplasia Patients.
AB  - MicroRNAs (miRNAs) are a class of short (~22nt), single stranded RNA molecules
      that function as post-transcriptional regulators of gene expression. MiRNAs can
      regulate a variety of important biological pathways, including: cellular
      proliferation, differentiation and apoptosis. Profiling of miRNA expression
      patterns was shown to be more useful than the equivalent mRNA profiles for
      characterizing poorly differentiated tumours. As such, miRNA expression
      "signatures" are expected to offer serious potential for diagnosing and
      prognosing cancers of any provenance. The aim of this study was to investigate
      the potential of using deregulation of urinary miRNAs in order to detect Prostate
      Cancer (PCa) among Benign Prostatic Hyperplasia (BPH). To identify the miRNA
      signatures specific for PCa, miRNA expression profiling of 8 PCa patients, 12 BPH
      patients and 10 healthy males was carried out using whole genome expression
      profiling. Differential expression of two individual miRNAs between healthy males
      and BPH patients was detected and found to possibly target genes related to PCa
      development and progression. The sensitivity and specificity of miR-1825 for
      detecting PCa among BPH individuals was found to be 60% and 69%, respectively.
      Whereas, the sensitivity and specificity of miR-484 were 80% and 19%,
      respectively. Additionally, the sensitivity and specificity for miR-1825/484 in
      tandem were 45% and 75%, respectively. The proposed PCa miRNA signatures may
      therefore be of great value for the accurate diagnosis of PCa and BPH. This
      exploratory study has identified several possible targets that merit further
      investigation towards the development and validation of diagnostically useful,
      non-invasive, urine-based tests that might not only help diagnose PCa but also
      possibly help differentiate it from BPH. 

PMID- 24563674
TI  - Radiation Exposure of Patients by Cone Beam CT during Endobronchial Navigation -
      A Phantom Study.
AB  - RATIONALE: Cone Beam Computed Tomography imaging has become increasingly
      important in many fields of interventional therapies. OBJECTIVE: Lung navigation
      study which is an uncommon soft tissue approach. METHODS: As no effective organ
      radiation dose levels were available for this kind of Cone Beam Computed
      Tomography application we simulated in our DynaCT (Siemens AG, Forchheim,
      Germany) suite 2 measurements including 3D acquisition and again for 3D
      acquisition and 4 endobronchial navigation maneuvers under fluoroscopy towards a
      nodule after the 8(th) segmentation in the right upper lobe over a total period
      of 20 minutes (min). These figures reflect the average complexity and time in our
      experience. We hereby describe the first time the exact protocol of lung
      navigation by a Cone Beam Computed Tomography approach. MEASUREMENT: The hereby
      first time measured body radiation doses in that approach showed very promising
      numbers between 0,98-1,15mSv giving specific lung radiation doses of 0,42-0,38
      mSv. MAIN RESULTS: These figures are comparable or even better to other lung
      navigation systems. Cone Beam Computed Tomography offers some unique features for
      lung interventionists as a realtime 1-step navigation system in an open structure
      feasible for endobronchial and transcutaneous approach. CONCLUSIONS: Due to this
      low level of radiation exposure Cone Beam Computed Tomography is expected to
      attract interventionists interested in using and guiding endobronchial or
      transcutaneous ablative procedures to peripheral endobronchial and other lung
      lesions.

PMID- 24563675
TI  - Modulation of Wnt Activity and Cell Physiology by Butyrate in LT97 Microadenoma
      Cells.
AB  - Dietary fiber intake is linked to a reduced risk of colon cancer. This effect may
      in part be due to butyrate, the fermentation product of fiber in the colon.
      Butyrate is a short-chain fatty acid that acts as a histone deacetylase inhibitor
      (HDACi). Butyrate induces apoptosis and represses clonal growth of colorectal
      cancer (CRC) cells, in a manner dependent upon the hyperactivation of Wnt /beta
      catenin signaling. While fiber has been linked to CRC prevention, in vitro
      studies on the action of butyrate have used CRC cell lines, instead of cells
      representative of earlier stages of colonic neoplasia, which are the likely
      target of butyrate-mediated preventive activity. The LT97 cell line is derived
      from a microadenoma, the earliest stage of colonic neoplasia from which cells can
      be isolated. We characterized LT97 cells with respect to effects of butyrate on
      Wnt signaling and apoptosis, and we determined whether modulation of CREB binding
      protein (CBP)/p300 activity influences the ability of butyrate to induce Wnt
      activity and apoptosis. We report that in LT97 cells, butyrate induces apoptosis,
      strongly upregulates Wnt signaling, and the upregulation of Wnt signaling is
      dependent upon CBP/p300 activity. In addition, findings from overexpression
      experiments suggest differences between CBP and p300 in their ability to
      influence Wnt signaling in LT97 cells; p300, but not CBP, stimulates basal Wnt
      activity. We also evaluated differences in gene expression between early stage
      LT97 cells and late stage metastatic SW620 CRC cells that exhibit markedly
      different cellular phenotypes. The comparative gene expression analyses revealed
      differences that may impact neoplastic progression and the sensitivity to the
      effects of butyrate. The findings have implications for the prevention of CRC by
      fiber/butyrate. 

PMID- 24563676
TI  - The Use of Androgen Deprivation Therapy (ADT) and Chemotherapeutic Agents in New
      Zealand Men with Prostate Cancer.
AB  - PURPOSE: To assess the patterns of use of androgen deprivation therapy (ADT) and
      chemotherapeutic agents in New Zealand men with prostate cancer. METHODS: Men
      diagnosed with prostate cancer between 2006 and 2011 were identified from the New
      Zealand Cancer Registry. Through data linkage with the Pharmaceutical Collection
      and the National Minimum Dataset information on subsidised anti-androgens,
      luteinising hormone-releasing hormone (LHRH) analogues, chemotherapeutic agents,
      and orchidectomy was retrieved. The frequency of ADT and chemotherapy use in the
      first year post-diagnosis was assessed by patients' age, ethnicity, and extent of
      disease at diagnosis. RESULTS: The study population included 15,947 men diagnosed
      with prostate cancer, of whom 4978 (31%) were prescribed ADT or chemotherapeutic
      agents. ADT was dispensed for 72% of men with metastatic disease. Only 24 (0.2%)
      men received chemotherapeutic agents. Men with advanced (regional or metastatic)
      disease older than 70 were more likely to receive anti-androgens only and to be
      treated with orchidectomy compared with younger men. Maori and Pacific men
      (compared with non-Maori/non-Pacific men) were more likely to receive
      pharmacologic ADT, and Maori men were also more likely to be treated with
      orchidectomy. CONCLUSIONS: It was expected that all men diagnosed with metastatic
      prostate cancer should be using ADT in the first year post-diagnosis. However,
      for more than one-fourth of men neither anti-androgens nor LHRH analogues were
      dispensed within this period. Chemotherapeutic agents were used very rarely, so
      it seems that both pharmacologic ADT and chemotherapy is under-utilised in New
      Zealand patients with advanced prostate cancer.

PMID- 24563677
TI  - Analysis and Modeling of Chromosome Congression During Mitosis in the
      Chemotherapy Drug Cisplatin.
AB  - The chemotherapy drug Cisplatin (cis-diamminedichloroplatinum(II)) induces
      crosslinks within and between DNA strands, and between DNA and nearby proteins.
      Therefore, Cisplatin-treated cells which progress into cell division may do so
      with altered chromosome mechanical properties. This could have important
      consequences for the successful completion of mitosis. Using Total Internal
      Reflection Fluorescence (TIRF) microscopy of live Cisplatin-treated Saccharomyces
      cerevisiae cells, we found that metaphase mitotic spindles have disorganized
      kinetochores relative to untreated cells, and also that there is increased
      variability in the chromosome stretching distance between sister centromeres.
      This suggests that chromosome stiffness may become more variable after Cisplatin
      treatment. We explored the effect of variable chromosome stiffness during mitosis
      using a stochastic model in which kinetochore microtubule dynamics were regulated
      by tension imparted by stretched sister chromosomes. Consistent with experimental
      results, increased variability of chromosome stiffness in the model led to
      disorganization of kinetochores in simulated metaphase mitotic spindles.
      Furthermore, the variability in simulated chromosome stretching tension was
      increased as chromosome stiffness became more variable. Because proper chromosome
      stretching tension may serve as a signal that is required for proper progression
      through mitosis, tension variability could act to impair this signal and thus
      prevent proper mitotic progression. Our results suggest a possible mitotic mode
      of action for the anti-cancer drug Cisplatin.

PMID- 24563679
TI  - Modeling the Mental Health Practice Change Preferences of Educators: A Discrete
      Choice Conjoint Experiment.
AB  - Schools are sometimes slow to adopt evidence-based strategies for improving the
      mental health outcomes of students. This study used a discrete-choice conjoint
      experiment to model factors influencing the decision of educators to adopt
      strategies for improving children's mental health outcomes. A sample of 1,010
      educators made choices between hypothetical mental health practice change
      strategies composed by systematically varying the four levels of 16 practice
      change attributes. Latent class analysis yielded two segments with different
      practice change preferences. Both segments preferred small-group workshops,
      conducted by engaging experts, teaching skills applicable to all students.
      Participants expressed little interest in Internet options. The support of
      colleagues, administrators, and unions exerted a strong influence on the practice
      change choices of both segments. The Change Ready segment, 77.1 % of the sample,
      was more intent on adopting new strategies to improve the mental health of
      students. They preferred that schools, rather than the provincial ministry of
      education, make practice change decisions, coaching was provided to all
      participants, and participants received post-training follow-up sessions. The
      Demand Sensitive segment (22.9 %) was less intent on practice change. They
      preferred that individual teachers make practice change decisions, recommended
      discretionary coaching, and chose no post-training follow-up support. This study
      emphasizes the complex social, organizational, and policy context within which
      educators make practice change decisions. Efforts to disseminate strategies to
      improve the mental health outcomes of students need to be informed by the
      preferences of segments of educators who are sensitive to different dimensions of
      the practice change process. In the absence of a broad consensus of educators,
      administrators, and unions, potentially successful practice changes are unlikely
      to be adopted.

PMID- 24563680
TI  - Fractured Identity: A Framework for Understanding Young Asian American Women's
      Self-harm and Suicidal Behaviors.
AB  - Despite the high suicide rate among young Asian American women, the reasons for
      this phenomenon remain unclear. This qualitative study explored the family
      experiences of 16 young Asian American women who are children of immigrants and
      report a history of self-harm and/or suicidal behaviors. Our findings suggest
      that the participants experienced multiple types of "disempowering parenting
      styles" that are characterized as: abusive, burdening, culturally disjointed,
      disengaged, and gender-prescriptive parenting. Tied to these family dynamics is
      the double bind that participants suffer. Exposed to multiple types of negative
      parenting, the women felt paralyzed by opposing forces, caught between a deep
      desire to satisfy their parents' expectations as well as societal expectations
      and to simultaneously rebel against the image of "the perfect Asian woman." Torn
      by the double bind, these women developed a "fractured identity," which led to
      the use of "unsafe coping" strategies. Trapped in a "web of pain," the young
      women suffered alone and engaged in self-harm and suicidal behaviors.

PMID- 24563678
TI  - Measurement science in the circulatory system.
AB  - The dynamics of the cellular and molecular constituents of the circulatory system
      are regulated by the biophysical properties of the heart, vasculature and blood
      cells and proteins. In this review, we discuss measurement techniques that have
      been developed to characterize the physical and mechanical parameters of the
      circulatory system across length scales ranging from the tissue scale
      (centimeter) to the molecular scale (nanometer) and time scales of years to
      milliseconds. We compare the utility of measurement techniques as a function of
      spatial resolution and penetration depth from both a diagnostic and research
      perspective. Together, this review provides an overview of the utility of
      measurement science techniques to study the spatial systems of the circulatory
      system in health and disease.

PMID- 24563681
TI  - Translation of oswestry disability index into Tamil with cross cultural
      adaptation and evaluation of reliability and validity(S).
AB  - STUDY DESIGN: Prospective longitudinal validation study. OBJECTIVE: To translate
      and cross-culturally adapt the Oswestry Disability Index (ODI) to the Tamil
      language (ODI-T), and to evaluate its reliability and construct validity. SUMMARY
      OF BACKGROUND DATA: ODI is widely used as a disease specific questionnaire in
      back pain patients to evaluate pain and disability. A thorough literature search
      revealed that the Tamil version of the ODI has not been previously published.
      METHODS: The ODI was translated and cross-culturally adapted to the Tamil
      language according to established guidelines. 30 subjects (16 women and 14 men)
      with a mean age of 42.7 years (S.D. 13.6; Range 22 - 69) with low back pain were
      recruited to assess the psychometric properties of the ODI-T Questionnaire.
      Patients completed the ODI-T, Roland-Morris disability questionnaire (RMDQ), VAS
      pain and VAS-disability at baseline and 24-72 hours from the baseline visit.
      RESULTS: The ODI-T displayed a high degree of internal consistency, with a
      Cronbach's alpha of 0.92. The test-retest reliability was high (n=30) with an ICC
      of 0.92 (95% CI, 0.84 to 0.96) and a mean re-test difference of 2.6 points lower
      on re-test. The ODI-T scores exhibited a strong correlation with the RMDQ scores
      (r = 0.82) p<0.01, VAS-P (r = 0.78) p<0.01 and VAS-D (r = 0.81) p<0.01. Moderate
      to low correlations were observed between the ODI-T and lumbar ROM (r = -0.27 to 
      0.53). All the hypotheses that were constructed apriori were supported.
      CONCLUSION: The Tamil version of the ODI Questionnaire is a valid and reliable
      tool that can be used to measure subjective outcomes of pain and disability in
      Tamil speaking patients with low back pain.

PMID- 24563682
TI  - Interactive 3D Analysis of Blood Vessel Trees and Collateral Vessel Volumes in
      Magnetic Resonance Angiograms in the Mouse Ischemic Hindlimb Model.
AB  - The quantitative analysis of blood vessel volumes from magnetic resonance
      angiograms (MRA) or MUCT images is difficult and time-consuming. This fact, when
      combined with a study that involves multiple scans of multiple subjects, can
      represent a significant portion of research time. In order to enhance analysis
      options and to provide an automated and fast analysis method, we developed a
      software plugin for the ImageJ and Fiji image processing frameworks that enables
      the quick and reproducible volume quantification of blood vessel segments. The
      novel plugin named Volume Calculator (VolCal), accepts any binary (thresholded)
      image and produces a three-dimensional schematic representation of the
      vasculature that can be directly manipulated by the investigator. Using MRAs of
      the mouse hindlimb ischemia model, we demonstrate quick and reproducible blood
      vessel volume calculations with 95 - 98% accuracy. In clinical settings this
      software may enhance image interpretation and the speed of data analysis and thus
      enhance intervention decisions for example in peripheral vascular disease or
      aneurysms. In summary, we provide a novel, fast and interactive quantification of
      blood vessel volumes for single blood vessels or sets of vessel segments with
      particular focus on collateral formation after an ischemic insult.

PMID- 24563684
TI  - BOOTSTRAP INFERENCE FOR NETWORK CONSTRUCTION WITH AN APPLICATION TO A BREAST
      CANCER MICROARRAY STUDY.
AB  - Gaussian Graphical Models (GGMs) have been used to construct genetic regulatory
      networks where regularization techniques are widely used since the network
      inference usually falls into a high-dimension-low-sample-size scenario. Yet,
      finding the right amount of regularization can be challenging, especially in an
      unsupervised setting where traditional methods such as BIC or cross-validation
      often do not work well. In this paper, we propose a new method - Bootstrap
      Inference for Network COnstruction (BINCO) - to infer networks by directly
      controlling the false discovery rates (FDRs) of the selected edges. This method
      fits a mixture model for the distribution of edge selection frequencies to
      estimate the FDRs, where the selection frequencies are calculated via model
      aggregation. This method is applicable to a wide range of applications beyond
      network construction. When we applied our proposed method to building a gene
      regulatory network with microarray expression breast cancer data, we were able to
      identify high-confidence edges and well-connected hub genes that could
      potentially play important roles in understanding the underlying biological
      processes of breast cancer.

PMID- 24563683
TI  - Contributors to Pediatric Obesity in Adolescence: More than just Energy
      Imbalance.
AB  - Disentangling the etiology of pediatric obesity continues to challenge
      researchers. Due to rapid growth and development, changes in the hormonal milieu,
      increased autonomy in feeding practices and greater interactions with
      environmental factors, adolescence is a particularly important period for the
      determination of body composition trajectories and the relationship to current
      and future obesity outcomes. A plethora of studies have focused on excess energy
      consumption and physical inactivity as they relate to weight and fat gain in
      adolescence. Although these "Big Two" have an impact, the increasing trends in
      pediatric obesity are not accounted for solely by increased energy intake and
      decreased physical activity. Indeed, under similar conditions of energy balance,
      inter-individual variation in fat accumulation has been consistently noted. It is
      becoming more evident that additional factors may contribute independently and/or
      synergistically to the increase in obesity. Such factors include (but are not
      limited to) metabolic programming in utero and in early childhood, the hormonal
      environment, endocrine disruptors, parental feeding practices, and the built
      environment. Our objective, therefore, is to investigate possible factors,
      particularly in adolescence that contributes to the increase in pediatric obesity
      beyond "The Big Two".

PMID- 24563686
TI  - Role of tryptophan side chain dynamics on the Trp-cage mini-protein folding
      studied by molecular dynamics simulations.
AB  - The 20 residue Trp-cage mini-protein is one of smallest proteins that adopt a
      stable folded structure containing also well-defined secondary structure
      elements. The hydrophobic core is arranged around a single central Trp residue.
      Despite several experimental and simulation studies the detailed folding
      mechanism of the Trp-cage protein is still not completely understood. Starting
      from fully extended as well as from partially folded Trp-cage structures a series
      of molecular dynamics simulations in explicit solvent and using four different
      force fields was performed. All simulations resulted in rapid collapse of the
      protein to on average relatively compact states. The simulations indicate a
      significant dependence of the speed of folding to near-native states on the side
      chain rotamer state of the central Trp residue. Whereas the majority of
      intermediate start structures with the central Trp side chain in a near-native
      rotameric state folded successfully within less than 100 ns only a fraction of
      start structures reached near-native folded states with an initially non-native
      Trp side chain rotamer state. Weak restraining of the Trp side chain dihedral
      angles to the state in the folded protein resulted in significant acceleration of
      the folding both starting from fully extended or intermediate conformations. The
      results indicate that the side chain conformation of the central Trp residue can
      create a significant barrier for controlling transitions to a near native folded
      structure. Similar mechanisms might be of importance for the folding of other
      protein structures. 

PMID- 24563685
TI  - De novo sequencing, assembly, and analysis of the root transcriptome of Persea
      americana (Mill.) in response to Phytophthora cinnamomi and flooding.
AB  - Avocado is a diploid angiosperm containing 24 chromosomes with a genome estimated
      to be around 920 Mb. It is an important fruit crop worldwide but is susceptible
      to a root rot caused by the ubiquitous oomycete Phytophthora cinnamomi.
      Phytophthora root rot (PRR) causes damage to the feeder roots of trees, causing
      necrosis. This leads to branch-dieback and eventual tree death, resulting in
      severe losses in production. Control strategies are limited and at present an
      integrated approach involving the use of phosphite, tolerant rootstocks, and
      proper nursery management has shown the best results. Disease progression of PRR
      is accelerated under high soil moisture or flooding conditions. In addition,
      avocado is highly susceptible to flooding, with even short periods of flooding
      causing significant losses. Despite the commercial importance of avocado, limited
      genomic resources are available. Next generation sequencing has provided the
      means to generate sequence data at a relatively low cost, making this an
      attractive option for non-model organisms such as avocado. The aims of this study
      were to generate sequence data for the avocado root transcriptome and identify
      stress-related genes. Tissue was isolated from avocado infected with P.
      cinnamomi, avocado exposed to flooding and avocado exposed to a combination of
      these two stresses. Three separate sequencing runs were performed on the Roche
      454 platform and produced approximately 124 Mb of data. This was assembled into
      7685 contigs, with 106 448 sequences remaining as singletons. Genes involved in
      defence pathways such as the salicylic acid and jasmonic acid pathways as well as
      genes associated with the response to low oxygen caused by flooding, were
      identified. This is the most comprehensive study of transcripts derived from root
      tissue of avocado to date and will provide a useful resource for future studies. 

PMID- 24563688
TI  - Angiopoietin-1 upregulates de novo expression of IL-1beta and Il1-Ra, and the
      exclusive release of Il1-Ra from human neutrophils.
AB  - The expression of the angiopoietin (Ang) receptor, Tie2, on both endothelial and
      inflammatory cells supports the idea that Ang signaling may play a fundamental
      role in initiating and maintaining the inflammatory response. We have previously
      shown that Ang1 and/or Ang2 alter the innate immune response by enhancing human
      neutrophil survival, chemotaxis and production of inflammatory cytokine
      interleukin-8 (IL-8) in vitro. Thus, we hypothesized that Ang1 and Ang2 could
      modulate other inflammatory signals in neutrophils, a possibility we explored
      through a gene-based assay looking at changes in the mRNA expression of 84
      inflammatory cytokines and their receptors. We observed that Ang1 (10(-8) M), but
      not Ang2, increased mRNA expression of prominent pro-inflammatory cytokine IL
      1beta and its natural antagonist IL-1RA, by up to 32.6- and 10.0-fold
      respectively, compared to PBS-control. The effects of Ang1 extended to the
      proteins, as Ang1 increased intracellular levels of precursor and mature IL
      1beta, and extracellular levels of IL-1RA proteins, by up to 4.2-, 5.0- and 4.4
      fold respectively, compared to PBS-control. Interestingly, Ang1 failed at
      inducing IL-1beta protein release or at increasing intracellular IL-1RA, but the
      ratio of IL-1RA to mature IL-1beta remained above 100-fold molar excess inside
      and outside the cells. The above-noted effects of Ang1 were mediated by MAP
      kinases, whereby inhibiting MEK1/2 lead to up to 70% effect reduction, whereas
      the blockade of p38MAPK activity doubled Ang1's effect. These findings suggest
      that Ang1 selectively alters the balance of neutrophil-derived inflammatory
      cytokines, favoring the blockade of IL-1 activity, a consideration for future
      therapies of inflammatory diseases. 

PMID- 24563687
TI  - Proline-hydroxylated hypoxia-inducible factor 1alpha (HIF-1alpha) upregulation in
      human tumours.
AB  - The stabilisation of HIF-alpha is central to the transcriptional response of
      animals to hypoxia, regulating the expression of hundreds of genes including
      those involved in angiogenesis, metabolism and metastasis. HIF-alpha is degraded
      under normoxic conditions by proline hydroxylation, which allows for recognition
      and ubiquitination by the von-Hippel-Lindau (VHL) E3 ligase complex. The aim of
      our study was to investigate the posttranslational modification of HIF-1alpha in
      tumours, to assess whether there are additional mechanisms besides reduced
      hydroxylation leading to stability. To this end we optimised antibodies against
      the proline-hydroxylated forms of HIF-1alpha for use in formalin fixed paraffin
      embedded (FFPE) immunohistochemistry to assess effects in tumour cells in vivo.
      We found that HIF-1alpha proline-hydroxylated at both VHL binding sites (Pro402
      and Pro564), was present in hypoxic regions of a wide range of tumours, tumour
      xenografts and in moderately hypoxic cells in vitro. Staining for hydroxylated
      HIF-1alpha can identify a subset of breast cancer patients with poorer prognosis
      and may be a better marker than total HIF-1alpha levels. The expression of
      unhydroxylated HIF-1alpha positively correlates with VHL in breast cancer
      suggesting that VHL may be rate-limiting for HIF degradation. Our conclusions are
      that the degradation of proline-hydroxylated HIF-1alpha may be rate-limited in
      tumours and therefore provides new insights into mechanisms of HIF upregulation.
      Persistence of proline-hydroxylated HIF-1alpha in perinecrotic areas suggests
      there is adequate oxygen to support prolyl hydroxylase domain (PHD) activity and
      proline-hydroxylated HIF-1alpha may be the predominant form associated with the
      poorer prognosis that higher levels of HIF-1alpha confer. 

PMID- 24563691
TI  - Two-Dimensional Tomography from Noisy Projections Taken at Unknown Random
      Directions.
AB  - Computerized tomography is a standard method for obtaining internal structure of
      objects from their projection images. While CT reconstruction requires the
      knowledge of the imaging directions, there are some situations in which the
      imaging directions are unknown, for example, when imaging a moving object. It is
      therefore desirable to design a reconstruction method from projection images
      taken at unknown directions. Another difficulty arises from the fact that the
      projections are often contaminated by noise, practically limiting all current
      methods, including the recently proposed diffusion map approach. In this paper,
      we introduce two denoising steps that allow reconstructions at much lower signal
      to-noise ratios (SNRs) when combined with the diffusion map framework. In the
      first denoising step we use principal component analysis (PCA) together with
      classical Wiener filtering to derive an asymptotically optimal linear filter. In
      the second step, we denoise the graph of similarities between the filtered
      projections using a network analysis measure such as the Jaccard index. Using
      this combination of PCA, Wiener filtering, graph denoising, and diffusion maps,
      we are able to reconstruct the two-dimensional (2-D) Shepp-Logan phantom from
      simulative noisy projections at SNRs well below their currently reported
      threshold values. We also report the results of a numerical experiment
      corresponding to an abdominal CT. Although the focus of this paper is the 2-D CT
      reconstruction problem, we believe that the combination of PCA, Wiener filtering,
      graph denoising, and diffusion maps is potentially useful in other signal
      processing and image analysis applications.

PMID- 24563689
TI  - Genome-wide high-throughput screening to investigate essential genes involved in
      methicillin-resistant Staphylococcus aureus Sequence Type 398 survival.
AB  - Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA)
      Sequence Type 398 (ST398) is an opportunistic pathogen that is able to colonize
      and cause disease in several animal species including humans. To better
      understand the adaptation, evolution, transmission and pathogenic capacity,
      further investigations into the importance of the different genes harboured by LA
      MRSA ST398 are required. In this study we generated a genome-wide transposon
      mutant library in an LA-MRSA ST398 isolate to evaluate genes important for
      bacterial survival in laboratory and host-specific environments. The transposon
      mutant library consisted of approximately 1 million mutants with around 140,000
      unique insertion sites and an average number of unique inserts per gene of 44.8.
      We identified LA-MRSA ST398 essential genes comparable to other high-throughput
      S. aureus essential gene studies. As ST398 is the most common MRSA isolated from
      pigs, the transposon mutant library was screened in whole porcine blood. Twenty
      four genes were specifically identified as important for bacterial survival in
      porcine blood. Mutations in 23 of these genes resulted in attenuated bacterial
      fitness. Seven of the 23 genes were of unknown function, whereas 16 genes were
      annotated with functions predominantly related to carbon metabolism, pH shock and
      a variety of regulations and only indirectly to virulence factors. Mutations in
      one gene of unknown function resulted in a hypercompetitive mutant. Further
      evaluation of these genes is required to determine their specific relevance in
      blood survival. 

PMID- 24563690
TI  - How often should we monitor for reliable detection of atrial fibrillation
      recurrence? Efficiency considerations and implications for study design.
AB  - OBJECTIVE: Although atrial fibrillation (AF) recurrence is unpredictable in terms
      of onset and duration, current intermittent rhythm monitoring (IRM) diagnostic
      modalities are short-termed and discontinuous. The aim of the present study was
      to investigate the necessary IRM frequency required to reliably detect recurrence
      of various AF recurrence patterns. METHODS: The rhythm histories of 647 patients
      (mean AF burden: 12 +/- 22% of monitored time; 687 patient-years) with
      implantable continuous monitoring devices were reconstructed and analyzed. With
      the use of computationally intensive simulation, we evaluated the necessary IRM
      frequency to reliably detect AF recurrence of various AF phenotypes using IRM of
      various durations. RESULTS: The IRM frequency required for reliable AF detection
      depends on the amount and temporal aggregation of the AF recurrence (p<0.0001) as
      well as the duration of the IRM (p<0.001). Reliable detection (>95% sensitivity)
      of AF recurrence required higher IRM frequencies (>12 24-hour; >6 7-day; >4 14
      day; >3 30-day IRM per year; p<0.0001) than currently recommended. Lower IRM
      frequencies will under-detect AF recurrence and introduce significant bias in the
      evaluation of therapeutic interventions. More frequent but of shorter duration,
      IRMs (24-hour) are significantly more time effective (sensitivity per monitored
      time) than a fewer number of longer IRM durations (p<0.0001). CONCLUSIONS:
      Reliable AF recurrence detection requires higher IRM frequencies than currently
      recommended. Current IRM frequency recommendations will fail to diagnose a
      significant proportion of patients. Shorter duration but more frequent IRM
      strategies are significantly more efficient than longer IRM durations. CLINICAL
      TRIAL REGISTRATION URL: Unique identifier: NCT00806689.

PMID- 24563692
TI  - Kallikrein 5-mediated inflammation in rosacea: clinically relevant correlations
      with acute and chronic manifestations in rosacea and how individual treatments
      may provide therapeutic benefit.
AB  - Rosacea is a chronic inflammatory condition of facial skin estimated to affect
      more than 16 million Americans. Although the pathogenesis of rosacea is not fully
      understood, recent evidence in vitro as well as in vivo has supported the role of
      increased levels of the trypsin-like serine protease, kallikrein 5, in initiating
      an augmented inflammatory response in rosacea. The increase in the quantity and
      magnitude of biological activity of kallikrein 5 leads to production of greater
      quantities of cathelicidin (LL-37), an antimicrobial peptide associated with
      increases in innate cutaneous inflammation, vasodilation, and vascular
      proliferation, all of which are characteristic features of rosacea. In this
      article, the authors review the literature supporting the role of kallikrein 5 in
      the pathophysiology of rosacea, including how therapeutic interventions modulate
      the effects of kallikrein 5, thus providing further support for this
      pathophysiological model that at least partially explains many of the clinical
      features of cutaneous rosacea. 

PMID- 24563693
TI  - What's New in the Medicine Cabinet?: A Panoramic Review of Clinically Relevant
      Information for the Busy Dermatologist.
AB  - This article is the first in a periodic series of therapeutic topics with short
      reviews gleaned from major dermatology meetings, especially Scientific Poster
      Sessions, and is designed to provide information that may assist the readers in
      adapting information from the literature to their clinical practice. The topics
      covered in this issue are discussions of the clinical relevance of newer
      information about acne pathophysiology, acne in adult women, and topical
      corticosteroid spray formulations for chronic plaque psoriasis. 

PMID- 24563694
TI  - Safety and Efficacy of Facial Rejuvenation with Small Gel Particle Hyaluronic
      Acid with Lidocaine and AbobotulinumtoxinA in Post-Chemotherapy Patients: A Phase
      IV Investigator-initiated Study.
AB  - BACKGROUND: Due to advances in detection and treatment, approximately 70 percent
      of cancer patients are living more than five years after diagnosis. Research
      indicates that appearance worries are of great concern to cancer survivors
      impacting their quality of life. This is the first Phase IV investigator
      initiated study to investigate the safety and efficacy of facial rejuvenation
      with small gel particle hyaluronic acid with lidocaine and abobotulinumtoxinA in
      post-chemotherapy patients. METHODS: The safety and efficacy of facial
      rejuvenation with small gel particle hyaluronic acid with lidocaine and
      abobotulinumtoxinA was assessed in nine post-chemotherapy patients. Efficacy of
      small gel particle hyaluronic acid with lidocaine and abobotulinumtoxinA was
      measured at baseline, Week 2, and Week 8, using a wrinkle severity assessment
      score. Safety and tolerability of both products were assessed throughout the
      study by monitoring the occurrence of adverse events. RESULTS: Patients received
      a mean total of 2.4mL of small gel particle hyaluronic acid with lidocaine in the
      nasolabial folds and 57.8 Units of abobotulinumtoxinA to glabellar lines at
      baseline. Additionally, at Week 2, a mean total l.OmL of small gel particle
      hyaluronic acid with lidocaine was administered to four patients. The mean
      investigator's wrinkle severity assessment score at baseline was 2.22, indicating
      mild-to-moderate severity. At each of Weeks 2 and 8, there were significant
      improvements from baseline in wrinkle severity (p=0.004). Overall, small gel
      particle hyaluronic acid with lidocaine was well tolerated. Adverse events (i.e.,
      bruising, redness, swelling, pain, tenderness, itching or other adverse events)
      were localized, self-limiting, and resolved within 1 to 2 days. The only adverse
      event attributed to abobotulinumtoxinA was soreness and slight tenderness at an
      injection site reported in one patient. CONCLUSION: Both study products were well
      tolerated in post-chemotherapy patients with no significant adverse events. There
      was a clinically meaningful and statistically significant improvement in wrinkle
      severity at Week 2 post-administration as compared to baseline. This improvement
      was maintained in all patients at Week 8.

PMID- 24563695
TI  - The effect of incobotulinumtoxin a and dermal filler treatment on perception of
      age, health, and attractiveness of female faces.
AB  - OBJECTIVES: Facial age, health, and attractiveness assessments play a major role
      in human social interaction and affect the way we perceive and think about
      others. Modern cosmetic dermatology provides a bewildering array of facial
      treatment procedures with botulinum toxin type A and dermal filler application
      being the most requested. The authors sought to determine the effect of facial
      rejuvenation procedures, such as application of incobotulinumtoxin A and dermal
      filler injections, on people's perception of age, health, and attractiveness.
      METHODS: Ten women underwent three consecutive facial rejuvenation procedures
      with incobotulinumtoxin A, calcium hydroxylapatite, and a hyaluronic acid.
      Digital facial images were taken before treatment and after each subsequent
      treatment and presented to a total of 150 third-party assessors who judged the
      images for age, health, and attractiveness. RESULTS: Each procedure was
      associated with a significant reduction in perceived age and an increase in
      perceived health and attractiveness compared with pre-treatment images. The
      effects were cumulative such that faces perceived as the youngest, healthiest,
      and most attractive had received all three treatments, followed in descending
      order by incobotulinumtoxin A and calcium hydroxylapatite treatment, and
      incobotulinumtoxin A alone. CONCLUSION: The authors demonstrate that naive judges
      are readily able to perceive the effect of nonsurgical facial rejuvenation
      procedures with incobotulinumtoxin A, calcium hydroxylapatite, and hyaluronic
      acid in terms of age, health, and attractiveness judgments. These effects were
      greatest when incobotulinumtoxin A and dermal filler treatments were combined.

PMID- 24563696
TI  - Pyoderma gangrenosum leading to bilateral involvement of ears.
AB  - Pyoderma gangrenosum is a destructive inflammatory disease that commonly occurs
      in an idiopathic way. Its occurrence in the auricular area is very rare, although
      this fact does not seem to determine a different behavior of the disease with
      regard to ulcer aspects and response to treatment. The authors report the case of
      a patient with pyoderma gangrenosum affecting both earlobes. The patient
      responded well to treatment with oral prednisone and has not shown relapses after
      a six-month follow-up. 

PMID- 24563697
TI  - Hyperpigmented follicular papules and bullae in an immunocompromised infant.

PMID- 24563698
TI  - Exploring the role of SlrR and SlrA in the SinR epigenetic switch.
AB  - BACTERIAL BIOFILMS ARE BECOMING A SIGNIFICANT SOCIETAL PROBLEM: biofilms form
      dental plaque, coat ships causing biofouling, and cling onto medical instruments
      and implants. Understanding how these surface-bound communities are formed is
      crucial for the development of suitable strategies for their dispersal. At the
      heart of a switch that commits Bacilli and related species to form biofilms is a
      transcriptional regulator called SinR and its multiple antagonists. In this
      addendum, we discuss an alternative model to account for how one of the
      antagonists is regulated by controlled proteolysis.

PMID- 24563699
TI  - Targeting secretion to the apical surface by mDia1-built actin tracks.
AB  - The apical surface of secretory tubular epithelia is a dynamic cellular domain
      where massive membrane turnover takes place during exocytosis and its subsequent
      compensatory endocytosis. This extensive membrane flow poses a difficulty in
      targeting secretory vesicles efficiently to a narrow apical domain. We have
      studied how actin filaments mediate the secretory process in the murine exocrine
      pancreas, which produces and secretes digestive enzymes that are deposited into
      the intestine. We show that cargo-filled secretory vesicles move over bundles of
      linear actin cables from their storage areas to the apical membrane of pancreatic
      acinar cells. mDia1, a linear actin nucleator of the Formin family, was
      identified as the generator of these structures. The active form of mDia1
      localizes to the apical surface, and the microfilament bundles it forms emanate
      from the apical surface and extend into the cytoplasm, generating polarized
      secretion tracks. These bundles ensure orderly progression of exocytosis, since
      the apical targeting of pancreatic vesicles is compromised in their absence, and
      vesicles fuse with each other to generate compound, membrane-associated secretory
      structures. 

PMID- 24563700
TI  - Giant virus in the sea: Extending the realm of Megaviridae to Viridiplantae.
AB  - The viral nature of the first "giant virus," Mimivirus, was realized in 2003, 10
      y after its initial isolation from the water of a cooling tower in Bradford, UK.
      Soon after its genome was sequenced, the mining of the Global Ocean Sampling
      environmental sequence database revealed that the closest relatives of Mimivirus,
      only known to infect Acanthamoeba, were to be found in the sea. These predicted
      marine Mimivirus relatives remained elusive until 2010, with the first genomic
      characterization of a virus infecting a heterotrophic unicellular eukaryote, the
      microflagellate grazer Cafeteria roenbergensis. The genome analysis of a virus
      (PgV) infecting the common unicellular algae Phaeocystis globosa now shows that
      it is a bona fide member of the Mimivirus family (i.e., the Megaviridae),
      extending the realm of these giant viruses to abundant blooming phytoplankton
      species. Despite its smaller genome size (460 kb encoding 434 proteins), PgV
      exhibits the most intriguing feature of the previously characterized Megaviridae:
      an associated virophage. However, the 19-kb virophage genome, devoid of a capsid
      gene, is packaged in the PgV particle and propagated as a "viral plasmid," the
      first ever described. The PgV genome also exhibits the duplication of "core
      genes," normally present as single copies and a putative new type of mobile
      element. In a DNA polymerase phylogeny including representatives of the three
      cellular domains, PgV and the other Megaviridae cluster into their own clade
      deeply branching between domains Archaea and Eukarya domains, thus exhibiting the
      topology of a fourth domain in the Tree of Life. 

PMID- 24563701
TI  - New insights into the evolution and structure of Colletotrichum plant-like
      subtilisins (CPLSs).
AB  - The Colletotrichum plant-like subtilisins (CPLSs) are a family of proteins found
      only in species of the phytopathogenic fungus Colletotrichum. CPLSs have high
      similarity to plant subtilisins and our previous work has shown that they were
      acquired by an ancient horizontal gene transfer event from plants. The rapid
      growth of sequence data in public databases enabled us to reexamine the structure
      and evolution of the CPLSs. A new plant subtilisin structural model aided us in
      refining the tertiary structure of CPLSs. Also, new information about protein
      interactions of plant subtilisin has provided new insights into the putative
      function of CPLSs. The availability of new genome sequences of members of the
      genus Colletotrichum gave us the opportunity to further validate our hypothesis
      that the CPLSs are unique to the Colletotrichum lineage. Together, this
      information furthers our knowledge of the potential role of the CPLSs in
      pathogenicity and the role of HGT in the genome evolution of plant pathogenic
      fungi. 

PMID- 24563703
TI  - How rapid is aphid-induced signal transfer between plants via common mycelial
      networks?
AB  - Arbuscular mycorrhizal (AM) fungi are important plant mutualists that can connect
      roots of neighboring plants to form common mycelial networks. A recent study
      demonstrated that these networks can act as conduits for aphid-induced signals
      between plants, activating chemical defenses in uninfested neighboring plants so
      that they become unattractive to aphids but attractive to their enemies
      (parasitoids). The benefit to the neighboring plants will increase if the signal
      speed is rapid, enabling them to respond before aphids attack. Here, we determine
      the speed of aphid-induced signal transfer between plants infested with aphids
      ("donor") and neighboring aphid-free plants that were either connected or
      unconnected to the donor via a common mycelial network. Induced changes in plant
      volatiles from neighbors connected to donors started within 24 h of aphid
      infestation of donors. This demonstrates a rapid signal, implying potential
      benefit to plants receiving the signal, and raises intriguing ecological and
      evolutionary questions. 

PMID- 24563702
TI  - Phenotypic diversification by gene silencing in Phytophthora plant pathogens.
AB  - Advances in genome sequencing technologies have enabled generation of
      unprecedented information on genome content and organization. Eukaryote genomes
      in particular may contain large populations of transposable elements (TEs) and
      other repeated sequences. Active TEs can result in insertional mutations, altered
      transcription levels and ectopic recombination of DNA. The genome of the oomycete
      plant pathogen, Phytophthora infestans, contains vast numbers of TE sequences.
      There are also hundreds of predicted disease-promoting effector proteins,
      predominantly located in TE-rich genomic regions. Expansion of effector gene
      families is also a genomic signature of related oomycetes such as P. sojae. Deep
      sequencing of small RNAs (sRNAs) from P. infestans has identified sRNAs derived
      from all families of transposons, highlighting the importance of RNA silencing
      for maintaining these genomic invaders in an inactive form. Small RNAs were also
      identified from specific effector encoding genes, possibly leading to RNA
      silencing of these genes and variation in pathogenicity and virulence toward
      plant resistance genes. Similar findings have also recently been made for the
      distantly related species, P. sojae. Small RNA "hotspots" originating from arrays
      of amplified gene sequences, or from genes displaying overlapping antisense
      transcription, were also identified in P. infestans. These findings suggest a
      major role for RNA silencing processes in the adaptability and diversification of
      these economically important plant pathogens. Here we review the latest progress
      and understanding of gene silencing in oomycetes with emphasis on transposable
      elements and sRNA-associated events. 

PMID- 24563704
TI  - Mind the gut: Dietary impact on germline stem cells and fertility.
AB  - Animals thrive in environments where food resources are abundant. While this
      correlation between population growth and food abundance is well established,
      much less is known about the influence of diet quality on physiological and
      developmental programs that support animal reproduction. Here we discuss dietary
      impact on fertility, and highlight a recent report on the activity of a nuclear
      receptor that protects against dietary metabolites to maintain germline stem cell
      integrity and reproduction. 

PMID- 24563705
TI  - Glucocorticoid receptor regulation of action selection and prefrontal cortical
      dendritic spines.
AB  - We recently reported that prolonged exposure to the glucocorticoid receptor (GR)
      ligand corticosterone impairs decision-making that is dependent on the predictive
      relationship between an action and its outcome (Gourley et al.; Proceedings of
      the National Academy of Sciences, 2012). Additionally, acute GR blockade, when
      paired with action-outcome conditioning, also blocks new learning. We then showed
      that dendritic spines in the prelimbic prefrontal cortex remodeled under both
      conditions. Nonetheless, the relationship between deep-layer dendritic spines and
      outcome-based decision-making remains opaque. We report here that a history of
      prolonged corticosterone exposure increases dendritic spine density in deep-layer
      prelimbic cortex. When spines are imaged simultaneously with corticosteroid
      exposure (i.e., without a washout period), dendritic spine densities are,
      however, reduced. Thus, the morphological response of deep-layer prelimbic
      cortical neurons to prolonged corticosteroid exposure may be quite dynamic, with
      spine elimination during a period of chronic exposure and spine proliferation
      during a subsequent washout period. We provide evidence, using a Rho-kinase
      inhibitor, that GR-mediated dendritic spine remodeling is causally related to
      complex decision-making. Finally, we conclude this report with evidence that a
      history of early-life (adolescent) GR blockade, unlike acute blockade in
      adulthood, enhances subsequent outcome-based decision-making. Together, our
      findings suggest that physiological levels of GR binding enable an organism to
      learn about the predictive relationship between an action and its outcome, but a
      history of GR blockade may, under some circumstances, also have beneficial
      consequences. 

PMID- 24563706
TI  - Unlocking the secrets of the delta2 glutamate receptor: A gatekeeper for synaptic
      plasticity in the cerebellum.
AB  - Long-term changes in synaptic transmission in the central nervous system, such as
      long-term potentiation and long-term depression (LTD), are believed to underlie
      learning and memory in vivo. Despite intensive research, the precise molecular
      mechanisms underlying these phenomena have remained unclear. LTD is most commonly
      caused by the endocytosis of postsynaptic AMPA-type glutamate receptors,
      triggered by activity-induced serine phosphorylation of the GluA2 subunit.
      Interestingly, cerebellar LTD, which occurs at synapses between parallel fibers
      (PFs; axons of granule cells) and Purkinje cells, is unique in requiring an
      additional type of glutamate receptor, the delta2 receptor (GluD2). Cbln1 was
      recently identified as a GluD2 ligand that regulates PF synapse formation and
      maintenance. However, how GluD2 induces downstream signaling in Purkinje cells to
      regulate LTD induction is unknown. We here present evidence that GluD2 reduces
      the tyrosine phosphorylation level of the GluA2 subunit via PTPMEG, a protein
      tyrosine phosphatase that binds to GluD2's C-terminus. We also found that the
      serine phosphorylation of GluA2, a crucial step for AMPA-receptor endocytosis,
      requires prior tyrosine dephosphorylation. Thus, GluD2 may serve as a gatekeeper
      for LTD induction by coordinating interactions between GluA2's 2 phosphorylation
      sites. 

PMID- 24563707
TI  - Callose deposition and symplastic connectivity are regulated prior to lateral
      root emergence.
AB  - Root growth is critical for the effective exploitation of the rhizosphere and
      productive plant growth. Our recent work(1) showed that root architecture was
      dependent upon the degree of symplastic connectivity between neighboring cells
      during the specification of lateral root primordia and was affected by genes
      regulating callose deposition at plasmodesmata (PD). Here we provide additional
      evidence that both symplastic connectivity and callose are also important during
      the later phase of lateral root development: emergence. Callose
      immunolocalization assays indicated that transient symplastic isolation of the
      primordium occur immediately prior to emergence through the overlaying tissues to
      produce the mature lateral root.(1) Here we could corroborate these results by
      analyzing the mobility of a symplastic tracer and the expression of PD genes in
      lateral roots and in response to auxins. Moreover, we show that altering callose
      deposition affects the number of emerged lateral roots suggesting that PD
      regulation is important for emergence. 

PMID- 24563708
TI  - Decision making in C. elegans chemotaxis to alkaline pH: Competition between two
      sensory neurons, ASEL and ASH.
AB  - Monitoring of environmental and tissue pH is critical for animal survival. The
      nematode, Caenorhabditis elegans (C. elegans), is attracted to mildly alkaline
      pH, but avoids strongly alkaline pH. However, little is known about how the
      behavioral switching or decision making occurs. Genetic dissection and Ca(2+)
      imaging have previously demonstrated that ASEL and ASH are the major sensory
      neurons responsible for attraction and repulsion, respectively. Here we report
      that unlike C. elegans wild type, mutants deficient in ASEL or ASH were repelled
      by mildly alkaline pH, or were attracted to strongly alkaline pH, respectively.
      These results suggest that signals through ASEL and ASH compete to determine the
      animal's alkaline-pH chemotaxis. Furthermore, mutants with 2 ASEL neurons were
      more efficiently attracted to mildly alkaline pH than the wild type with a single
      ASEL neuron, indicating that higher activity of ASEL induces stronger attraction
      to mildly alkaline pH. This stronger attraction was overridden by normal activity
      of ASH, suggesting that ASH-mediated avoidance dominates ASEL-mediated
      attraction. Thus, C. elegans chemotactic behaviors to alkaline pH seems to be
      determined by signal strengths from the sensory neurons ASEL and ASH, and the
      behavior decision making seems to be the result of competition between the 2
      sensory neurons. 

PMID- 24563709
TI  - A G-protein alpha subunit, GOA-1, plays a role in C. elegans avoidance behavior
      of strongly alkaline pH.
AB  - The ability of animals to avoid strongly alkaline pH is critical for survival.
      However, the means by which they sense high pH has not been determined. We have
      previously found that the nematode Caenorhabditis elegans (C. elegans) avoids
      environmental pH above 10.5. Detection involves ASH nociceptive neurons as the
      major sensors. Upon stimulation, transient receptor potential vanilloid-type
      (TRPV) ion channels encoded by osm-9 and ocr-2 play an essential role in Ca(2+)
      entry into ASH. Here we report that C. elegans mutants deficient in a G-protein
      alpha subunit, GOA-1, failed to avoid strongly alkaline pH with normal Ca(2+)
      influx into ASH. These results suggest that GOA-1 regulates signal transmission
      downstream of Ca(2+) influx through OSM-9/OCR-2 TRPV channels in ASH. 

PMID- 24563710
TI  - Temperature and excitable cells: Testable predictions from a thermodynamic
      perspective.
AB  - Temperature affects a host of biological processes, one of which is the
      conduction velocity of action potentials (AP). The velocity-temperature profile
      of APs has remained remarkably conserved across excitable animal and plant cells.
      Herein, we will not analyze this behavior in terms of temperature sensitivities
      of single molecules (e.g., ion channels), but rather we present a
      phenomenological thermodynamic interpretation. By assuming that APs are acoustic
      phenomena, one arrives at testable predictions about the temperature-dependence
      of the macroscopic material properties of the excitable cell membrane. These
      material properties set constraints on the excitability of a cell membrane and
      allow us to hypothesize about its typical relaxation timescales. The presented
      approach-by virtue of its thermodynamic nature-is by no means limited to
      temperature. It applies equally well to all thermodynamic variables (e.g.,
      mechanical stretch, pH, ion concentrations, etc.) and to underline this argument
      we discuss some implications and predictions for sensory physiology. 

PMID- 24563711
TI  - Falsification of the ionic channel theory of hair cell transduction.
AB  - The hair cell provides the transduction of mechanical vibrations in the balance
      and acoustic sense of all vertebrates that swim, walk, or fly. The current theory
      places hair cell transduction in a mechanically controlled ion channel. Although
      the theory of a mechanical input modulating the flow of ions through an ion pore
      has been a useful tool, it is falsified by experimental data in the literature
      and can be definitively falsified by a proposed experiment. 

PMID- 24563713
TI  - No effect of inter-group conflict on within-group harmony in non-human primates.
AB  - It has been a longstanding assumption that the threat of extra-group conflict can
      promote the expression of socio-positive behavior and cohesion within animal
      groups. I conducted a comparative analysis on the effect of inter-group conflict
      (indexed by home range overlap) on within-group affiliation levels (indexed by
      time engaged in allogrooming) in a sample of 48 primate species. There was no
      association between the 2 variables in a phylogenetic generalized least squares
      regression. I conclude that inter-group conflict may at best elicit short-term
      immediate changes in affiliation levels, but permanently elevated cohesion
      appears unique to humans with their large-scale social integration and scaled up
      inter-group conflict. 

PMID- 24563712
TI  - Parallel mechanisms for direct and indirect membrane protein trafficking by
      synucleins.
AB  - More than 2 decades of work have yet to conclusively determine the physiological
      role of the synuclein proteins, even though these abundant brain constituents are
      participants in a broad array of cellular processes. Among proposed physiological
      roles is a functional interaction between the synuclein proteins and monoamine
      transporters contributing to transporter trafficking through direct protein
      protein interactions. Recent work shows that an antagonistic effect of the
      synuclein proteins on the secretory functions of the endoplasmic reticulum and
      the Golgi apparatus appears to simultaneously influence trafficking of the
      dopamine transporter and other membrane proteins. Here, we highlight these new
      findings in view of the broader literature identifying the role of synucleins in
      protein trafficking and suggest emerging themes for ongoing and future work in
      the field of synuclein biology. 

PMID- 24563714
TI  - Rab11 as a modulator of synaptic transmission.
AB  - Many neurodegenerative disorders are characterized by synaptic dysfunction
      preceding general neuronal loss and subsequent cognitive or behavioral anomalies.
      Much recent research has been aimed at understanding the early underlying
      processes leading to dysfunction at the synapse, as this knowledge would likely
      inform interventions that could potentially slow progression and delay onset of
      disease. We have recently reported that synaptic dysfunction in a Drosophila
      melanogaster model of Huntington's disease (HD) can be prevented by enhanced
      neuronal expression of Rab11, a Rab family GTPase involved in endosomal
      recycling, which complements studies that have found disrupted Rab11 activity in
      several models of this disorder. Indeed, inhibition of Rab11 function in
      fibroblasts of HD patients has been observed to perturb vesicle formation from
      recycling endosomes. Therefore, our study investigated a potential role of Rab11
      in synaptic dysfunction prior to the onset of HD symptoms, with the aim of
      finding a possible early intervention to disease progression. We found that Rab11
      ameliorates synaptic dysfunction due to expression of mutant huntingtin-the
      causative protein in HD-by normalizing synaptic vesicle size, which consequently
      ameliorates locomotor deficits in Drosophila larvae. Here we further consider
      these results and the implications this work has on potential therapeutic
      intervention in HD and other neurodegenerative disorders. 

PMID- 24563716
TI  - The "Clever Hans Phenomenon" revisited.
AB  - In the first decade of the 20th century, a horse named Hans drew worldwide
      attention in Berlin as the first and most famous "speaking" and thinking animal.
      Hans solved calculations by tapping numbers or letters with his hoof in order to
      answer questions. Later on, it turned out that the horse was able to give the
      correct answer by reading the microscopic signals in the face of the questioning
      person. This observation caused a revolution and as a consequence, experimenters
      avoided strictly any face-to-face contact in studies about cognitive abilities of
      animals-a fundamental lesson that is still not applied rigorously. 

PMID- 24563715
TI  - Dock protein family in brain development and neurological disease.
AB  - The family of dedicator of cytokinesis (Dock), a protein family that belongs to
      the atypical Rho guanine nucleotide exchange factors (GEFs) for Rac and/or Cdc42
      GTPases, plays pivotal roles in various processes of brain development. To date,
      11 members of Docks have been identified in the mammalian system. Emerging
      evidence has suggested that members of the Dock family are associated with
      several neurodegenerative and neuropsychiatric diseases, including Alzheimer
      disease and autism spectrum disorders. This review summarizes recent advances on
      the understanding of the roles of the Dock protein family in normal and diseased
      processes in the nervous system. Furthermore, interacting proteins and the
      molecular regulation of Docks are discussed. 

PMID- 24563717
TI  - Fructose-1,6-bisphosphatase, Malate Dehydrogenase, Isocitrate Lyase,
      Phosphoenolpyruvate Carboxykinase, Glyceraldehyde-3-phosphate Dehydrogenase, and
      Cyclophilin A are secreted in Saccharomyces cerevisiae grown in low glucose.
AB  - Our previous studies demonstrated that the key gluconeogenic enzyme fructose-1,6
      bisphosphatase is secreted when Saccharomyces cerevisiae are starved of glucose
      for a prolonged period of time. In this study, we showed that malate
      dehydrogenase, isocitrate lyase, phosphoenolpyruvate carboxykinase,
      glyceraldehyde-3-phosphate dehydrogenase, and cyclophilin A are also secreted in
      glucose-starved cells. Thus, both gluconeogenic and non-gluconeogenic enzymes are
      secreted via the non-classical pathway. 

PMID- 24563718
TI  - Variability of non-symbiotic and truncated hemoglobin genes from the genome of
      cultivated monocots.
AB  - Non-symbiotic (nsHb) and truncated (tHb) hemoglobins (Hbs) have been detected in
      a variety of land plants. The evolution of land plant nsHbs and tHbs at the
      protein level is well documented; however, little is known about the evolution of
      genes coding for these proteins. For example, the variability of the land plant
      nshb and thb genes is not known. Here, we report the variability of the nshb and
      thb genes from the genome of the cultivated monocots Brachypodium distachyon,
      Hordeum vulgare (barley), Oryza glaberrima (rice), O. rufipogon (rice), O. sativa
      (rice) var indica, O. sativa (rice) var japonica, Panicum virgatum (switchgrass),
      Setaria italica (foxtail millet), Sorghum bicolor (sorghum), Triticum aestivum
      (wheat), and Zea mays ssp. mays (maize) using sequence comparison and
      computational methods. Our results revealed that in cultivated monocots
      variability is higher in nshbs than in thbs, and suggest that major substitution
      events that occurred during the evolution of the cultivated monocot hbs were A->G
      and T->C transitions and that these genes evolved under the effect of neutral
      selection. 

PMID- 24563719
TI  - Unexpected functions of lncRNAs in gene regulation.
AB  - Long non-coding RNAs (lncRNAs) are a group of molecules that function in gene
      regulation in yeast, plants and mammals. The precise mechanisms of action for
      lncRNAs, however, remain largely unclear. The GAL gene cluster has been used as a
      model system to study the function of these molecules in Saccharomyces
      cerevisiae, with a historical focus on lncRNA-dependent repression. Strikingly,
      in characterizing the role of the RNA helicase Dbp2, we discovered that the GAL
      lncRNAs could also promote transcriptional activation of the targeted GAL protein
      coding genes. Interestingly, these lncRNAs help determine how quickly the GAL
      genes can be induced in response to galactose, without altering final steady
      state transcript levels. This unexpected finding suggests that one role for
      lncRNAs is to promote the timing of gene expression. Herein, we discuss our
      discoveries in the context of current models of lncRNA functions in eukaryotes,
      with a key emphasis on future challenges for genomic research. 

PMID- 24563720
TI  - Exocyst proteins in cytokinesis: Regulation by Rab11.
AB  - The Exocyst is an octameric protein complex comprised of Sec3, Sec5, Sec6, Sec8,
      Sec10, Sec15, Exo70, and Exo84 subunits.(1, 2) This complex was first identified
      in budding yeast where it acts to target vesicles to the bud tip and the cleavage
      furrow.(3) Here, we show that all Exocyst subunits are required for cytokinesis
      in mammalian cells. We further show that a subset of Exocyst proteins are
      differentially regulated by Rab11, consistent with recent studies implicating
      Rab11 vesicles in Exocyst protein trafficking. 

PMID- 24563721
TI  - Ultrastructure of microglia-synapse interactions in the HIV-1 Tat-injected murine
      central nervous system.
AB  - The destruction of normal synaptic architecture is the main pathogenetic
      substrate in HIV-associated neurocognitive disorder (HAND), but the sequence of
      cellular events underlying this outcome is not completely understood. Our recent
      work in a mouse model of HAND using a single intraparenchymal injection of the
      HIV-1 regulatory protein trans-activator of transcription revealed increased
      microglial phagocytosis that was accompanied by an increased release of pro
      inflammatory cytokines and elimination of dendritic spines in vivo, thus
      suggesting that microglia-synapse interactions could be dysregulated in HAND.
      Here, we further examine the relationships between microglia and synaptic
      structures in our mouse model, at high spatial resolution using
      immunocytochemical electron microscopy. Our ultrastructural analysis reveals the
      prevalence of putative microglial filopodial protrusions, which are targeting
      excitatory and inhibitory synapses, some of which contain phagocytic inclusions
      at various distances from their distal extremities to the microglial cell bodies.
      These observations thus suggest that cell-to-cell contacts mediated by microglial
      filopodia might be a crucial preliminary step in the elimination of synaptic
      structures in a neuroinflammatory milieu that occurs in HAND. 

PMID- 24563722
TI  - Rho GTPase: A molecular compass for directional cell migration.
AB  - Ras GTPases and phosphatidylinositol 3-kinases mediate intracellular signaling in
      directed cell migration. During chemotaxis, cells spatially control the
      activation of Ras/PI (3,4,5)-trisphosphate (PIP3) signaling and translate
      extracellular chemical gradients into intracellular signal cascades. This process
      is called directional sensing, and enables persistent cell migration with
      extraordinary sensitivity in shallow, unstable gradients of chemoattractants. In
      our recent study, we identified a Rho GTPase and its guanine nucleotide exchange
      factor (GEF) as molecular modulators that transmit signals from G protein-coupled
      receptors to Ras/PIP3 signaling pathways. The proteins spatially stabilize Ras
      activation and PIP3 production toward higher concentrations of chemoattractants.
      Unlike known roles of Rho GTPases and GEFs, the function of these proteins in
      directional sensing is independent of the actin cytoskeleton and cell morphology.
      Our findings provide novel mechanistic insight into the precision of directional
      cell migration. 

PMID- 24563723
TI  - Preparation and activities of macromolecule conjugates of the CCR5 antagonist
      Maraviroc.
AB  - CCR5 antagonists are among the most advanced approaches in HIV therapy and may
      also be relevant to treatment of graft-versus-host disease and Staphylococcus
      aureus infection. To expand the potential of the only approved CCR5 antagonist,
      Maraviroc, we studied derivatives that would enable functional linkage of
      Maraviroc to long-lived carriers. Through targeted synthesis, we discovered an
      effective linkage site on Maraviroc and demonstrate the potential of these
      derivatives to prepare potent chemically programmed antibodies and PEGylated
      derivatives. The resulting compounds effectively neutralized a variety of HIV-1
      isolates. Both chemically programmed antibody and PEGylation approaches extend
      the neutralization activity of serum circulating Maraviroc. Derivation of a
      successful conjugation strategy for Maraviroc should further enable its use in
      chemically programmed vaccines, novel bispecific antibodies, and topical
      microbicides.

PMID- 24563724
TI  - Ultrafast Z-Spectroscopy for 129Xe NMR-Based Sensors.
AB  - When working with hyperpolarized species, it is often difficult to maintain a
      stable level of magnetization over consecutive experiments, which renders their
      detection at the trace level cumbersome, even when combined with chemical
      exchange saturation transfer (CEST). We report herein the use of ultra-fast Z
      spectroscopy as a powerful means to detect low concentrations of 129Xe NMR-based
      sensors and to measure the in-out xenon exchange. Modifications of the original
      sequence enable a multiplexed detection of several sensors, as well as the
      extraction of the exchange buildup rate constant in a single-shot fashion.

PMID- 24563725
TI  - Vibrational Excitations and Low Energy Electronic Structure of Epoxide-decorated
      Graphene.
AB  - We report infrared studies of adsorbed atomic oxygen (epoxide functional groups)
      on graphene. Two different systems are used as a platform to explore these
      interactions, namely, epitaxial graphene/SiC(0001) functionalized with atomic
      oxygen (graphene epoxide, GE) and chemically reduced graphene oxide (RGO). In the
      case of the model GE system, IR reflectivity measurements show that epoxide
      groups distort the graphene pi bands around the K-point, imparting a finite
      effective mass and contributing to a band gap. In the case of RGO, epoxide groups
      are found to be present following the reduction treatment by a combination of
      polarized IR reflectance and transmittance measurements. Similar to the GE
      system, a band gap in the RGO sample is observed as well.

PMID- 24563726
TI  - Prognostic value of 18F-FDG PET metabolic parameters in oropharyngeal squamous
      cell carcinoma.
AB  - OBJECTIVE: To evaluate whether pretreatment metabolic parameters obtained from
      positron emission tomography (PET) with [18F]fluorodeoxyglucose (FDG) can improve
      risk prediction for patients with oropharyngeal squamous cell carcinoma (OPSCC)
      treated with definitive intensity-modulated radiation therapy (IMRT). METHODS:
      Between 2003 and 2009, 86 patients with OPSCC had FDG-PET/CT prior to treatment
      with definitive IMRT. Chemotherapy was administered to 90 % of the patients.
      Metabolic tumor volume (MTV), total lesion glycolysis (TLG), maximum standardized
      uptake value (SUVmax), mean SUV (SUVmean), and inverse coefficient of variation
      (1/CoV) were analyzed for the primary tumor alone and the total of the primary
      tumor and involved lymph nodes. RESULTS: Median follow-up time for surviving
      patients was 41 months. On univariate analysis, total MTV and total TLG were
      significant predictors of disease-free survival (DFS) and overall survival (OS).
      SUVmax, SUVmean, and 1/CoV failed to predict DFS or OS. On multivariate analysis
      controlling for T- and N-classification, total MTV remained a significant
      predictor of DFS and OS. The optimal cutpoint for total MTV was 20.5 ml. A total
      MTV >20.5 ml was associated with a 4.13-fold increased risk of death (95 %
      confidence interval [CI], 2.12-8.05; p < 0.0001). Total MTV remained a
      significant predictor of DFS and OS for the subgroups with p16-positive (n = 25)
      and p16-negative (n = 18) cancer. CONCLUSION: Total MTV is an independent
      predictor of DFS and OS for patients with OPSCC treated with definitive
      radiotherapy. Total MTV remained predictive of DFS and OS for both p16-positive
      and p16-negative cancer.

PMID- 24563727
TI  - Imaging of prostate cancer: a platform for 3D co-registration of in-vivo MRI ex
      vivo MRI and pathology.
AB  - OBJECTIVES: Multi-parametric MRI is emerging as a promising method for prostate
      cancer diagnosis. prognosis and treatment planning. However, the localization of
      in-vivo detected lesions and pathologic sites of cancer remains a significant
      challenge. To overcome this limitation we have developed and tested a system for
      co-registration of in-vivo MRI, ex-vivo MRI and histology. MATERIALS AND METHODS:
      Three men diagnosed with localized prostate cancer (ages 54-72, PSA levels 5.1
      7.7 ng/ml) were prospectively enrolled in this study. All patients underwent 3T
      multi-parametric MRI that included T2W, DCE-MRI, and DWI prior to robotic
      assisted prostatectomy. Ex-vivo multi-parametric MRI was performed on fresh
      prostate specimen. Excised prostates were then sliced at regular intervals and
      photographed both before and after fixation. Slices were perpendicular to the
      main axis of the posterior capsule, i.e., along the direction of the rectal wall.
      Guided by the location of the urethra, 2D digital images were assembled into 3D
      models. Cancer foci, extra-capsular extensions and zonal margins were delineated
      by the pathologist and included in 3D histology data. A locally-developed
      software was applied to register in-vivo, ex-vivo and histology using an over
      determined set of anatomical landmarks placed in anterior fibro-muscular stroma,
      central. transition and peripheral zones. The mean root square distance across
      corresponding control points was used to assess co-registration error. RESULTS:
      Two specimens were pT3a and one pT2b (negative margin) at pathology. The software
      successfully fused in-vivo MRI. ex-vivo MRI fresh specimen and histology using
      appropriate (rigid and affine) transformation models with mean square error of
      1.59 mm. Coregistration accuracy was confirmed by multi-modality viewing using
      operator-guided variable transparency. CONCLUSION: The method enables successful
      co-registration of pre-operative MRI, ex-vivo MRI and pathology and it provides
      initial evidence of feasibility of MRI-guided surgical planning.

PMID- 24563728
TI  - Combined use of Ilizarov external fixation and Papineau technique for septic
      pseudoarthrosis of the distal tibia in a patient with diabetes mellitus.
AB  - The surgical treatment of open pilon fractures has a high complication rate
      especially in diabetic patients. In this article, we present a case of an
      infected tibial non-union after an open reduction and internal fixation in a
      diabetic patient, treated with Ilizarov external fixation combined with Papineau
      technique. Combined use of external fixation and Papineau technique can provide
      an alternative option for the treatment of septic pseudoarthrosis of the distal
      tibia. 

PMID- 24563729
TI  - Implicit and explicit avoidance in sexual trauma victims suffering from
      posttraumatic stress disorder: a pilot study.
AB  - BACKGROUND: Avoidance of stimuli that are associated with the traumatic event is
      a key feature of posttraumatic stress disorder (PTSD). Thus far, studies on the
      role of avoidance in the development and maintenance of PTSD focused primarily on
      strategic or explicit avoidance. However, patients may also show implicit
      avoidance behavior, which may remain even when explicit avoidance is reduced.
      OBJECTIVES: The present pilot study was designed to test the hypothesis that PTSD
      patients show implicit avoidance of threatening, trauma-related stimuli. In
      addition, it was tested whether this avoidance behavior also occurs for other
      stimuli. METHODS: The Approach-Avoidance Task was used as an indirect measure of
      avoidance. Participants were 16 women suffering from PTSD who had experienced a
      sexual trauma, and 23 healthy non-traumatized women. Using a joystick, they
      pulled pictures closer to themselves or pushed them away. The pictures varied in
      content, being either high-threat sexual, non-threat sexual, high-threat
      accident, or positive. RESULTS: Compared to control participants, PTSD patients
      avoided high-threat sexual pictures, and the degree of avoidance was predicted by
      self-reported arousal level. Moreover, PTSD patients with high levels of self
      reported explicit avoidance, depressive symptoms, and PTSD symptom severity also
      avoided high-threat accident pictures. CONCLUSIONS: These findings point to the
      possible importance of threat value instead of trauma-relatedness in explaining
      implicit avoidance. The results are discussed in light of cognitive-behavioral
      models of PTSD, and clinical implications are suggested.

PMID- 24563730
TI  - Is traumatic stress research global? A bibliometric analysis.
AB  - BACKGROUND: The representation of low- and middle-income countries (LMIC) in
      traumatic stress research is important to establish a global evidence base, build
      research capacity, and reduce the burden of unmet mental health needs around the
      world. Reviews of the traumatic stress literature up to 2002 showed trends toward
      globalization although LMIC were only marginally represented compared to high
      income countries (HIC). OBJECTIVE: To examine the global nature of current
      traumatic stress research. In particular, we were interested in the extent to
      which traumatic stress research is: (1) conducted in LMIC, (2) conducted by LMIC
      researchers, and (3) accessible to them. METHOD: Using the databases PubMed,
      PsychInfo, and PILOTS, we systematically searched for peer-reviewed articles on
      traumatic stress published in any language in the year 2012. Out of the 3,123
      unique papers identified, we coded a random sample (N=1,000) for study, author,
      article, and journal characteristics. RESULTS: Although our sample involved
      research in 56 different countries, most papers (87%) involved research in HIC,
      with 51% of all papers describing studies in the United States. In 88% of the
      papers, the author team was affiliated with HIC only. Less than 5% of all author
      teams involved collaborations between HIC and LMIC researchers. Moreover, 45% of
      the articles on LMIC studies published by a HIC corresponding author did not
      involve any LMIC co-authors. LMIC researchers appeared to publish empirical
      studies in lower impact journals. Of the 1,000 articles in our sample, 32% were
      open access and 10% were made available via different means; over half of the
      papers were not accessible without subscription. CONCLUSIONS: Traumatic stress
      research is increasingly global but still strongly dominated by HIC. Important
      opportunities to build capacity in LMIC appear to be missed. Implications toward
      more international traumatic stress research are discussed.

PMID- 24563733
TI  - Noninferiority trials: clinical understandings and misunderstandings.

PMID- 24563732
TI  - Extracellular vesicles from a muscle cell line (C2C12) enhance cell survival and
      neurite outgrowth of a motor neuron cell line (NSC-34).
AB  - INTRODUCTION: There is renewed interest in extracellular vesicles over the past
      decade or 2 after initially being thought of as simple cellular garbage cans to
      rid cells of unwanted components. Although there has been intense research into
      the role of extracellular vesicles in the fields of tumour and stem cell biology,
      the possible role of extracellular vesicles in nerve regeneration is just in its
      infancy. BACKGROUND: When a peripheral nerve is damaged, the communication
      between spinal cord motor neurons and their target muscles is disrupted and the
      result can be the loss of coordinated muscle movement. Despite state-of-the-art
      surgical procedures only approximately 10% of adults will recover full function
      after peripheral nerve repair. To improve upon such results will require a better
      understanding of the basic mechanisms that influence axon outgrowth and the
      interplay between the parent motor neuron and the distal end organ of muscle. It
      has previously been shown that extracellular vesicles are immunologically
      tolerated, display targeting ligands on their surface, and can be delivered in
      vivo to selected cell populations. All of these characteristics suggest that
      extracellular vesicles could play a significant role in nerve regeneration.
      METHODS: We have carried out studies using 2 very well characterized cell lines,
      the C2C12 muscle cell line and the motor neuron cell line NSC-34 to ask the
      question: Do extracellular vesicles from muscle influence cell survival and/or
      neurite outgrowth of motor neurons? CONCLUSION: Our results show striking effects
      of extracellular vesicles derived from the muscle cell line on the motor neuron
      cell line in terms of neurite outgrowth and survival.

PMID- 24563731
TI  - An association of metabolic syndrome constellation with cellular membrane
      caveolae.
AB  - Metabolic syndrome (MetS) is a cluster of metabolic abnormalities that can
      predispose an individual to a greater risk of developing type-2 diabetes and
      cardiovascular diseases. The cluster includes abdominal obesity, dyslipidemia,
      hypertension, and hyperglycemia - all of which are risk factors to public health.
      While searching for a link among the aforementioned malaises, clues have been
      focused on the cell membrane domain caveolae, wherein the MetS-associated active
      molecules are colocalized and interacted with to carry out designated biological
      activities. Caveola disarray could induce all of those individual metabolic
      abnormalities to be present in animal models and humans, providing a new target
      for therapeutic strategy in the management of MetS. 

PMID- 24555018
TI  - A domain sequence approach to pangenomics: applications to Escherichia coli.
AB  - The study of microbial pangenomes relies on the computation of gene families,
      i.e. the clustering of coding sequences into groups of essentially similar genes.
      There is no standard approach to obtain such gene families. Ideally, the gene
      family computations should be robust against errors in the annotation of genes in
      various genomes. In an attempt to achieve this robustness, we propose to cluster
      sequences by their domain sequence, i.e. the ordered sequence of domains in their
      protein sequence. In a study of 347 genomes from Escherichia coli we find on
      average around 4500 proteins having hits in Pfam-A in every genome, clustering
      into around 2500 distinct domain sequence families in each genome. Across all
      genomes we find a total of 5724 such families. A binomial mixture model approach
      indicates this is around 95% of all domain sequences we would expect to see in E.
      coli in the future. A Heaps law analysis indicates the population of domain
      sequences is larger, but this analysis is also very sensitive to smaller changes
      in the computation procedure. The resolution between strains is good despite the
      coarse grouping obtained by domain sequence families. Clustering sequences by
      their ordered domain content give us domain sequence families, who are robust to
      errors in the gene prediction step. The computational load of the procedure
      scales linearly with the number of genomes, which is needed for the future
      explosion in the number of re-sequenced strains. The use of domain sequence
      families for a functional classification of strains clearly has some potential to
      be explored. 

PMID- 24555020
TI  - Capecitabine-induced radiation recall phenomenon: a case report.
AB  - Radiation recall dermatitis is defined as an inflammatory reaction of the skin at
      the site of previous irradiation. Different drugs have been associated with
      triggering this phenomenon, and it can also affect other areas and organs where
      previous radiotherapy has been administered. The time gap between the
      inflammatory reaction and previous radiation can range from days to several
      years. We report a case of capecitabine-induced Radiation Therapy Oncology Group
      (RTOG) grade 4 (ulcerating dermatitis) recall skin toxicity of skin irradiated 3
      years previously. To our knowledge, this is the first reported case of
      capecitabine-induced RTOG grade 4 (ulcerating dermatitis) recall skin toxicity of
      previously irradiated skin. Clinicians should be aware of this phenomenon, even
      when considering patients for whom it has been a long time since previous
      radiation therapy. This unusual and late drug side effect should be borne in mind
      in the differential diagnosis and management of advanced-disease patients as it
      may be confused with local relapse or infectious complication of previously
      operated areas. 

PMID- 24563734
TI  - Mechanisms of mixed-lineage leukemia.
AB  - Advances in our understanding of the genetic determinants of leukemia have
      translated to better treatment options and improved survival of patients with
      acute myeloid and acute lymphoid leukemia. However, some leukemias, such as those
      bearing 11q23 (MLL) translocations, result in aggressive diseases with a
      relatively poor prognosis, despite improved treatments such as allogeneic
      hematopoietic stem cell transplantation. This article will briefly review the
      functions and regulation of wild-type MLL during normal hematopoiesis, while
      focusing on recent advances in our understanding of the molecular mechanisms
      governing MLL leukemias. The transcriptional targets, cooperating signaling
      pathways and molecular machinery involved in MLL-associated leukemias will be
      discussed, as well as how these may be harnessed for more personalized treatment
      of this disease.

PMID- 24555023
TI  - De novo genetic variation revealed in somatic sectors of single Arabidopsis
      plants.
AB  - Concern over the tremendous loss of genetic diversity among many of our most
      important crops has prompted major efforts to preserve seed stocks derived from
      cultivated species and their wild relatives.  Arabidopsis thaliana propagates
      mainly by self-fertilizing, and therefore, like many crop plants, theoretically
      has a limited potential for producing genetically diverse offspring. Despite
      this, inbreeding has persisted in Arabidopsis for over a million years suggesting
      that some underlying adaptive mechanism buffers the deleterious consequences of
      this reproductive strategy. Using presence-absence molecular markers we
      demonstrate that single Arabidopsis plants can have multiple genotypes. Sequence
      analyses reveal single nucleotide changes, loss of sequences and, surprisingly,
      acquisition of unique genomic insertions. Estimates based on quantitative
      analyses suggest that these genetically discordant sectors are very small but can
      have a complex genetic makeup. In ruling out more trivial explanations for these
      data, our findings raise the possibility that intrinsic drivers of genetic
      variation are responsible for the targeted sequence changes we detect. Given the
      evolutionary advantage afforded to populations with greater genetic diversity, we
      hypothesize that organisms that primarily self-fertilize or propagate clonally
      counteract the genetic cost of such reproductive strategies by leveraging a
      cryptic reserve of extra-genomic information. 

PMID- 24555036
TI  - Electrophysiological properties of mouse and epitope-tagged human cardiac sodium
      channel Na v1.5 expressed in HEK293 cells.
AB  - BACKGROUND: The pore-forming subunit of the cardiac sodium channel, Na v1.5, has
      been previously found to be mutated in genetically determined arrhythmias. Na
      v1.5 associates with many proteins that regulate its function and cellular
      localisation. In order to identify more in situ Na v1.5 interacting proteins,
      genetically-modified mice with a high-affinity epitope in the sequence of Na v1.5
      can be generated. METHODS: In this short study, we (1) compared the biophysical
      properties of the sodium current (I Na) generated by the mouse Na v1.5 (mNa v1.5)
      and human Na v1.5 (hNa v1.5) constructs that were expressed in HEK293 cells, and
      (2) investigated the possible alterations of the biophysical properties of the
      human Na v1.5 construct that was modified with specific epitopes. RESULTS: The
      biophysical properties of mNa v1.5 were similar to the human homolog. Addition of
      epitopes either up-stream of the N-terminus of hNa v1.5 or in the extracellular
      loop between the S5 and S6 transmembrane segments of domain 1, significantly
      decreased the amount of I Na and slightly altered its biophysical properties.
      Adding green fluorescent protein (GFP) to the N-terminus did not modify any of
      the measured biophysical properties of hNa v1.5. CONCLUSIONS: These findings have
      to be taken into account when planning to generate genetically-modified mouse
      models that harbour specific epitopes in the gene encoding mNa v1.5.

PMID- 24555034
TI  - Reactive oxygen production induced by near-infrared radiation in three strains of
      the Chl d-containing cyanobacterium Acaryochloris marina.
AB  - Cyanobacteria in the genus Acaryochloris have largely exchanged Chl a with Chl d,
      enabling them to harvest near-infrared-radiation (NIR) for oxygenic
      photosynthesis, a biochemical pathway prone to generate reactive oxygen species
      (ROS). In this study, ROS production under different light conditions was
      quantified in three Acaryochloris strains (MBIC11017, HICR111A and the novel
      strain CRS) using a real-time ethylene detector in conjunction with addition of 2
      keto-4-thiomethylbutyric acid, a substrate that is converted to ethylene when
      reacting with certain types of ROS. In all strains, NIR was found to generate
      less ROS than visible light (VIS). More ROS was generated if strains MBIC11017
      and HICR111A were adapted to NIR and then exposed to VIS, while strain CRS
      demonstrated the opposite behavior. This is the very first study of ROS
      generation and suggests that Acaryochloris can avoid a considerable amount of
      light-induced stress by using NIR instead of VIS for its photosynthesis, adding
      further evolutionary arguments to their widespread appearance. 

PMID- 24555024
TI  - II. Capsular vaso-mimicry formed by transgenic mammary tumor spheroids implanted
      ectopically into mouse dorsal skin fold: implications for cellular mechanisms of
      metastasis.
AB  - Most cancer patients die of metastatic disease, not primary tumors, while
      biological mechanisms leading to metastases remain unclear and effective
      therapies are missing. Using a mouse dorsal skin chamber model we had observed
      that tumor growth and vasculature formation could be influenced by the way in
      vitro cultured (avascular) spheroids of N202 breast tumor cells were implanted;
      co-implantation of lactating breast tissue created stimulating microenvironment,
      whereas the absence of the graft resulted in temporary tumor dormancy. This
      report addressed the issue of cellular mechanisms of the vasculogenic switch that
      ended the dormancy. In situ ultrastructural analysis revealed that the tumors
      survived in ectopic microenvironment until some of host and tumor stem cells
      evolved independently into cells initiating the vasculogenic switch. The tumor
      cells that survived and proliferated under hypoxic conditions for three weeks
      were supported by erythrogenic autophagy of others. However, the host
      microenvironment first responded as it would to non-immunogenic foreign bodies,
      i.e., by encapsulating the tumor spheroids with collagen-producing fibroblasts.
      That led to a form of vaso-mimicry consisting of tumor cells amid tumor-derived
      erythrosomes (synonym of erythrocytes), megakaryocytes and platelets, and
      encapsulating them all, the host fibroblasts. Such capsular vaso-mimicry could
      potentially facilitate metastasis by fusing with morphologically similar
      lymphatic vessels or veins. Once incorporated into the host circulatory system,
      tumor cells could be carried away passively by blood flow, regardless of their
      genetic heterogeneity. The fake vascular segment would have permeability
      properties different from genuine vascular endothelium. The capsular vaso-mimicry
      was different from vasculogenic mimicry earlier observed in metastases-associated
      malignant tumors where channels formed by tumor cells were said to contain
      circulating blood. Structures similar to the vasculogenic mimicry were seen here
      as well but contained non-circulating erythrosomes formed between tumor nodules.
      The host's response to the implantation included coordinated formation of new
      vessels and peripheral nerves. 

PMID- 24555042
TI  - The Binding Ring Illusion: assimilation affects the perceived size of a circular
      array.
AB  - Our perception of an object's size arises from the integration of multiple
      sources of visual information including retinal size, perceived distance and its
      size relative to other objects in the visual field. This constructive process is
      revealed through a number of classic size illusions such as the Delboeuf
      Illusion, the Ebbinghaus Illusion and others illustrating size constancy. Here we
      present a novel variant of the Delbouef and Ebbinghaus size illusions that we
      have named the Binding Ring Illusion. The illusion is such that the perceived
      size of a circular array of elements is underestimated when superimposed by a
      circular contour - a binding ring - and overestimated when the binding ring
      slightly exceeds the overall size of the array. Here we characterize the stimulus
      conditions that lead to the illusion, and the perceptual principles that underlie
      it. Our findings indicate that the perceived size of an array is susceptible to
      the assimilation of an explicitly defined superimposed contour. Our results also
      indicate that the assimilation process takes place at a relatively high level in
      the visual processing stream, after different spatial frequencies have been
      integrated and global shape has been constructed. We hypothesize that the Binding
      Ring Illusion arises due to the fact that the size of an array of elements is not
      explicitly defined and therefore can be influenced (through a process of
      assimilation) by the presence of a superimposed object that does have an explicit
      size. 

PMID- 24555044
TI  - Stability, orientation and position preference of the stem region (residues 689
      703) in Hepatitis C Virus (HCV) envelope glycoprotein E2: a molecular dynamics
      study.
AB  - Envelope glycoproteins of Hepatitis C Virus (HCV) play an important role in the
      virus assembly and initial entry into host cells. Conserved charged residues of
      the E2 transmembrane (TM) domain were shown to be responsible for the
      heterodimerization with envelope glycoprotein E1. Despite intensive research on
      both envelope glycoproteins, the structural information is still not fully
      understood. Recent findings have revealed that the stem (ST) region of E2 also
      functions in the initial stage of the viral life cycle. We have previously shown
      the effect of the conserved charged residues on the TM helix monomer of E2. Here,
      we extended the model of the TM domain by adding the adjacent ST segment.
      Explicit molecular dynamics simulations were performed for the E2 amphiphilic
      segment of the ST region connected to the putative TM domain (residues 683-746).
      Structural conformation and behavior are studied and compared with the nuclear
      magnetic resonance (NMR)-derived segment of E2 ( 2KQZ.pdb). We observed that the
      central helix of the ST region (residues 689 - 703) remained stable as a helix in
      plane to the lipid bilayer. Furthermore, the TM domain appeared to provide
      minimal contribution to the structural stability of the amphipathic region. This
      study also provides insight into the orientation and positional preferences of
      the ST segment with respect to the membrane lipid-water interface. 

PMID- 24555046
TI  - Continuous and intermittent exposure of neonatal rat calvarial cells to PTHrP (1
      36) inhibits bone nodule mineralization in vitro by downregulating bone
      sialoprotein expression via the cAMP signaling pathway.
AB  - The development and growth of the skeleton in the absence of parathyroid-hormone
      related protein (PTHrP) is abnormal.  The shortening of appendicular bones in
      PTHrP gene null mice is explained by an effect of PTHrP on endochondral bone
      growth.  Whether or not PTHrP influences intramembranous ossification is less
      clear.  The purpose of this study was to determine the effect of exogenous PTHrP
      on intramembranous ossification in vitro.  Neonatal rat calvarial cells
      maintained in primary cell culture conditions that permit spontaneous formation
      of woven bone nodules by intramembranous ossification were studied. The
      expression of PTHrP, parathyroid hormone 1 receptor (PTH1R), and alkaline
      phosphatase (AP) by osteogenic cells in developing nodules and the effects of
      PTHrP (1-36) on nodule development was determined over 3-18 days. PTHrP and PTH1R
      were detected colonies of osteogenic cells on culture day three, and AP was
      detected on day six. PTHrP and its receptor were localized in pre-osteoblasts,
      osteoblasts, and osteocytes, and AP activity was detected in pre-osteoblasts and
      osteoblasts but not osteocytes. Continuous and intermittent exposure to PTHrP (1
      36) decreased the number of mineralized bone nodules and bone sialoprotein (BSP)
      mRNA and protein, but had no effect on the number of AP-positive osteogenic cell
      colonies, cell proliferation, apoptosis, or osteopontin (OPN) mRNA. These results
      demonstrate that osteogenic cells that participate in the formation of woven bone
      nodules in vitro exhibit PTHrP and PTH1R before they demonstrate AP activity.
      Exogenous PTHrP (1-36) inhibits the mineralization of woven bone deposited during
      bone nodule formation in vitro, possibly by reducing the expression of BSP. 

PMID- 24555047
TI  - Internet-delivered eye movement desensitization and reprocessing (iEMDR): an open
      trial.
AB  - Recent research indicates internet-delivered cognitive behavioural therapy (iCBT)
      can reduce symptoms of post traumatic stress disorder (PTSD). This study examined
      the efficacy of an internet-delivered treatment protocol that combined iCBT and
      internet-delivered eye movement desensitization and reprocessing (iEMDR), in an
      uncontrolled trial. Eleven of the 15 participants completed post-treatment
      questionnaires. Large effect sizes were found from pre-treatment to 3-month
      follow-up ( d = 1.03 - 1.61) on clinician-assessed and self-reported measures of
      PTSD, anxiety and distress, with moderate effect sizes ( d = 0.59 - 0.70) found
      on measures of depression and disability. At post-treatment, 55% of the
      participants no longer met criteria for PTSD and this was sustained at follow-up.
      Symptom worsening occurred in 3 of 15 (20%) of the sample from pre- to post
      treatment; however, these participants reported overall symptom improvement by
      follow-up. Future research directions for iEMDR are discussed. 

PMID- 24555051
TI  - Intrathecal Drug Delivery (ITDD) systems for cancer pain.
AB  - Intrathecal drug delivery is an effective pain management option for patients
      with chronic and cancer pain. The delivery of drugs into the intrathecal space
      provides superior analgesia with smaller doses of analgesics to minimize side
      effects while significantly improving quality of life. This article aims to
      provide a general overview of the use of intrathecal drug delivery to manage
      pain, dosing recommendations, potential risks and complications, and growing
      trends in the field. 

PMID- 24555051
TI  - Intrathecal Drug Delivery (ITDD) systems for cancer pain.
AB  - Intrathecal drug delivery is an effective pain management option for patients
      with chronic and cancer pain. The delivery of drugs into the intrathecal space
      provides superior analgesia with smaller doses of analgesics to minimize side
      effects while significantly improving quality of life. This article aims to
      provide a general overview of the use of intrathecal drug delivery to manage
      pain, dosing recommendations, potential risks and complications, and growing
      trends in the field. 

PMID- 24555055
TI  - Differences in antibiotic use and knowledge between adolescent and adult mothers
      in Ecuador.
AB  - OBJECTIVES:  To investigate the differences in antibiotic use and knowledge
      between adolescent and adult mothers of children under the age of 5 years in
      Ecuador. METHODS:  A cross sectional study was performed in four health centers
      and hospitals. Mothers of children under five years, seeking medical attention
      their child's upper respiratory tract infection (URI), were included. The data
      was collected through interviews, using a structured questionnaire. The
      questionnaire covered the topics knowledge of antibiotic treatment, risk and
      resistance.  RESULTS:  777 mothers were included in the study, of which 15.8%
      were adolescent and 84.1% adult mothers. There were significant differences in
      the social and economic characteristics of the mothers (p <= 0.05), with
      adolescent mothers being more likely to have an incomplete high school education
      and lack of basic services in their home. Significant differences between these
      groups were found in adherence to treatment, knowledge about risks associated
      with antibiotic use, and having heard of antibiotic resistance. Among the adult
      mothers, 83.5% reported correct adherence, 28.5% were knowledgeable about risks
      associated with antibiotic use, and 29.3% had heard of antibiotic resistance.
      Among the adolescent mothers, these numbers were 75.4%, 15.0%, and 19.8%,
      respectively. CONCLUSIONS:  To develop successful interventions, it is crucial to
      understand the factors causing differences in antibiotic use and knowledge
      between mothers.

PMID- 24555058
TI  - IsoCleft Finder - a web-based tool for the detection and analysis of protein
      binding-site geometric and chemical similarities.
AB  - IsoCleft Finder is a web-based tool for the detection of local geometric and
      chemical similarities between potential small-molecule binding cavities and a non
      redundant dataset of ligand-bound known small-molecule binding-sites. The non
      redundant dataset developed as part of this study is composed of 7339 entries
      representing unique Pfam/PDB-ligand (hetero group code) combinations with known
      levels of cognate ligand similarity. The query cavity can be uploaded by the user
      or detected automatically by the system using existing PDB entries as well as
      user-provided structures in PDB format. In all cases, the user can refine the
      definition of the cavity interactively via a browser-based Jmol 3D molecular
      visualization interface. Furthermore, users can restrict the search to a subset
      of the dataset using a cognate-similarity threshold. Local structural
      similarities are detected using the IsoCleft software and ranked according to two
      criteria (number of atoms in common and Tanimoto score of local structural
      similarity) and the associated Z-score and p-value measures of statistical
      significance. The results, including predicted ligands, target proteins,
      similarity scores, number of atoms in common, etc., are shown in a powerful
      interactive graphical interface. This interface permits the visualization of
      target ligands superimposed on the query cavity and additionally provides a table
      of pairwise ligand topological similarities. Similarities between top scoring
      ligands serve as an additional tool to judge the quality of the results obtained.
      We present several examples where IsoCleft Finder provides useful functional
      information. IsoCleft Finder results are complementary to existing approaches for
      the prediction of protein function from structure, rational drug design and x-ray
      crystallography. IsoCleft Finder can be found at:
      http://bcb.med.usherbrooke.ca/isocleftfinder. 

PMID- 24555059
TI  - Eco-physiological adaptation of dominant tree species at two contrasting karst
      habitats in southwestern China.
AB  - The purpose of this study was to investigate the eco-physiological adaptation of
      indigenous woody species to their habitats in karst areas of southwestern China.
      Two contrasting forest habitats were studied: a degraded habitat in Daxiagu and a
      well-developed habitat in Tianlongshan, and the eco-physiological characteristics
      of the trees were measured for three growth seasons. Photosynthetic rate (Pn),
      stomatal conductance (gs), and transpiration rate (Tr) of the tree species in
      Daxiagu were 2-3 times higher than those in Tianlongshan under ambient
      conditions. However, this habitat effect was not significant when measurements
      were taken under controlled conditions. Under controlled conditions, Pn, gs, and
      Tr of the deciduous species were markedly higher than those for the evergreen
      species. Habitat had no significant effect on water use efficiency (WUE) or
      photochemical characteristics of PSII. The stomatal sensitivity of woody species
      in the degraded habitat was much higher than that in the well-developed habitat.
      Similarly, the leaf total nitrogen (N) and phosphorus (P) contents expressed on
      the basis of either dry mass or leaf area were also much higher in Daxiagu than
      they were in Tianlongshan. The mass-based leaf total N content of deciduous
      species was much higher than that of evergreen species, while leaf area-based
      total N and P contents of evergreens were significantly higher than those of
      deciduous species. The photosynthetic nitrogen- and phosphorus-use efficiencies
      (PNUE and PPUE) of deciduous species were much higher than those of evergreens.
      Further, the PPUE of the woody species in Tianlongshan was much higher than that 
      of the woody species in Daxiagu. The results from three growth seasons imply that
      the tree species were able to adapt well to their growth habitats. Furthermore,
      it seems that so-called "temporary drought stress" may not occur, or may not be
      severe for most woody plants in karst areas of southwestern China. 

PMID- 24555061
TI  - Discovery of continental-scale travelling waves and lagged synchrony in geometrid
      moth outbreaks prompt a re-evaluation of mountain birch/geometrid studies.
AB  - The spatio-temporal dynamics of populations of two 9-10 year cyclic-outbreaking
      geometrids, Operophtera brumata and Epirrita autumnata in mountain birch forests
      in northern Fennoscandia, have been studied since the 1970's by a Swedish
      Norwegian research team and, during the last decade, by Norwegian and Finnish
      research teams. Some of the early results have been challenged by the Norwegian
      team. To examine the base for disagreements, five of the papers published by the
      Norwegian team (2004-2011) are reviewed. It is found that conclusions in these
      papers are questionable or data could not be interpreted fully because two
      decisive traits in the spatio-temporal behaviour of outbreaks of the two species
      were not considered. 

PMID- 24555062
TI  - An a posteriori measure of network modularity.
AB  - Measuring modularity is important to understand the structure of networks, and
      has an important number of real-world implications. However, several measures
      exists to assess the modularity, and give both different modularity values and
      different modules composition. In this article, I propose an a posteriori measure
      of modularity, which represents the ratio of interactions between members of the
      same modules vs. members of different modules. I apply this measure to a large
      dataset of 290 ecological networks, to show that it gives new insights about
      their modularity. 

PMID- 24555062
TI  - An a posteriori measure of network modularity.
AB  - Measuring the modularity of networks, and how it deviates from random
      expectations, important to understand their structure and emerging properties.
      Several measures exist to assess modularity, which when applied to the same
      network, can return both different modularity values (i.e. different estimates of
      how modular the network is) and different module compositions (i.e. different
      groups of species forming said modules). More importantly, as each optimization
      method uses a different optimization criterion, there is a need to have an a
      posteriori measure serving as an equivalent of a goodness-of-fit. In this
      article, I propose such a measure of modularity, which is simply defined as the
      ratio of interactions established between members of the same modules vs. members
      of different modules. I apply this measure to a large dataset of 290 ecological
      networks representing host-parasite (bipartite) and predator-prey (unipartite)
      interactions, to show how the results are easy to interpret and present
      especially to a broad audience not familiar with modularity analyses, but still
      can reveal new features about modularity and the ways to measure it. 

PMID- 24555064
TI  - Identification and molecular characterization of a novel Chlamydomonas
      reinhardtii mutant defective in chlorophyll biosynthesis.
AB  - The green micro-alga Chlamydomonas reinhardtii is an elegant model organism to
      study all aspects of oxygenic photosynthesis. Chlorophyll (Chl) and heme are
      major tetrapyrroles that play an essential role in energy metabolism in
      photosynthetic organisms and are synthesized via a common branched tetrapyrrole
      biosynthetic pathway. One of the enzymes in the pathway is Mg chelatase (MgChel)
      which inserts Mg (2+) into protoporphyrin IX (PPIX, proto) to form magnesium
      protoporphyrin IX (MgPPIX, Mgproto), the first biosynthetic intermediate in the
      Chl branch. MgChel is a multimeric enzyme that consists of three subunits
      designated CHLD, CHLI and CHLH. Plants have two isozymes of CHLI (CHLI1 and
      CHLI2) which are 70%-81% identical in protein sequences. Although the functional
      role of CHLI1 is well characterized, that of CHLI2 is not. We have isolated a non
      photosynthetic light sensitive mutant 5A7 by random DNA insertional mutagenesis
      that is devoid of any detectable Chl. PCR based analyses show that 5A7 is missing
      the CHLI1 gene and at least eight additional functionally uncharacterized genes.
      5A7 has an intact CHLI2 gene. Complementation with a functional copy of the CHLI1
      gene restored Chl biosynthesis, photo-autotrophic growth and light tolerance in
      5A7. We have identified the first chli1 (chli1-1) mutant of Chlamydomonas
      reinhardtii and in green algae. Our results show that in the wild type
      Chlamydomonas CHLI2 protein amount is lower than that of CHLI1 and the chli1-1
      mutant has a drastic reduction in CHLI2 protein levels although it possesses the
      CHLI2 gene. Our chli1-1 mutant opens up new avenues to explore the functional
      roles of CHLI1 and CHLI2 in Chl biosynthesis in Chlamydomonas, which has never
      been studied before. 

PMID- 24555068
TI  - Curcumin reduces prostaglandin E2, matrix metalloproteinase-3 and proteoglycan
      release in the secretome of interleukin 1beta-treated articular cartilage.
AB  - OBJECTIVE: Curcumin (diferuloylmethane) is a phytochemical with potent anti
      inflammatory and anti-oxidant properties, and has therapeutic potential for the
      treatment of a range of inflammatory diseases, including osteoarthritis (OA). The
      aim of this study was to determine whether non-toxic concentrations of curcumin
      can reduce interleukin-1beta (IL-1beta)-stimulated inflammation and catabolism in
      an explant model of cartilage inflammation. METHODS: Articular cartilage explants
      and primary chondrocytes were obtained from equine metacarpophalangeal joints.
      Curcumin was added to monolayer cultured primary chondrocytes and cartilage
      explants in concentrations ranging from 3MUM-100MUM. Prostaglandin E 2 (PGE 2)
      and matrix metalloproteinase (MMP)-3 release into the secretome of IL-1beta
      stimulated explants was measured using a competitive ELISA and western blotting
      respectively. Proteoglycan (PG) release in the secretome was measured using the
      1,9-dimethylmethylene blue (DMMB) assay. Cytotoxicity was assessed with a
      live/dead assay in monolayer cultures after 24 hours, 48 hours and five days, and
      in explants after five days. RESULTS: Curcumin induced chondrocyte death in
      primary cultures (50MUM p<0.001 and 100MUM p<0.001) after 24 hours. After 48
      hours and five days, curcumin (>=25MUM) significantly increased cell death (
      p<0.001 both time points). In explants, curcumin toxicity was not observed at
      concentrations up to and including 25MUM after five days. Curcumin (>=3MUM)
      significantly reduced IL-1beta-stimulated PG ( p<0.05) and PGE 2 release (
      p<0.001) from explants, whilst curcumin (>=12MUM) significantly reduced MMP-3
      release ( p<0.01). CONCLUSION: Non-cytotoxic concentrations of curcumin exert
      anti-catabolic and anti-inflammatory effects in cartilage explants.

PMID- 24555072
TI  - The first structure in a family of peptidase inhibitors reveals an unusual Ig
      like fold.
AB  - We report the crystal structure solution of the Intracellular Protease Inhibitor
      (IPI) protein from Bacillus subtilis, which has been reported to be an inhibitor
      of the intracellular subtilisin Isp1 from the same organism. The structure of IPI
      is a variant of the all-beta, immunoglobulin (Ig) fold. It is possible that IPI
      is important for protein-protein interactions, of which inhibition of Isp1 is
      one. The intracellular nature of ISP is questioned, because an alternative ATG
      codon in the ipi gene would produce a protein with an N-terminal extension
      containing a signal peptide. It is possible that alternative initiation exists,
      producing either an intracellular inhibitor or a secreted form that may be
      associated with the cell surface.  Homologues of the IPI protein from other
      species are multi-domain proteins, containing signal peptides and domains also
      associated with the bacterial cell-surface. The cysteine peptidase inhibitors
      chagasin and amoebiasin also have Ig-like folds, but their topology differs
      significantly from that of IPI, and they share no recent common ancestor. A model
      of IPI docked to Isp1 shows similarities to other subtilisin:inhibitor complexes,
      particularly where the inhibitor interacts with the peptidase active site. 

PMID- 24555073
TI  - Prevalence of antibiotic-resistant E. coli in retail chicken: comparing
      conventional, organic, kosher, and raised without antibiotics.
AB  - Retail poultry products are known sources of antibiotic-resistant Escherichia
      coli, a major human health concern. Consumers have a range of choices for
      poultry, including conventional, organic, kosher, and raised without antibiotics
      (RWA) - designations that are perceived to indicate differences in quality and
      safety. However, whether these categories vary in the frequency of contamination
      with antibiotic-resistant E. coli is unknown. We examined the occurrence of
      antibiotic-resistant E. coli on raw chicken marketed as conventional, organic,
      kosher and RWA. From April - June 2012, we purchased 213 samples of raw chicken
      from 15 locations in the New York City metropolitan area. We screened E. coli
      isolates from each sample for resistance to 12 common antibiotics. Although the
      organic and RWA labels restrict the use of antibiotics, the frequency of
      antibiotic-resistant E. coli tended to be only slightly lower for RWA, and
      organic chicken was statistically indistinguishable from conventional products
      that have no restrictions. Kosher chicken had the highest frequency of antibiotic
      resistant E. coli, nearly twice that of conventional products, a result that
      belies the historical roots of kosher as a means to ensure food safety. These
      results indicate that production methods influence the frequency of antibiotic
      resistant E. coli on poultry products available to consumers. Future research to
      identify the specific practices that cause the high frequency of antibiotic
      resistant E. coli in kosher chicken could promote efforts to reduce consumer
      exposure to this potential pathogen. 

PMID- 24555074
TI  - Did the elimination of lead from petrol reduce crime in the USA in the 1990s?
AB  - This article assesses the evidence for the hypothesis that a decline in all types
      of crime since the early 1990s in the USA was a consequence of removing lead from
      petrol between 1975 and 1985. It describes ecological and econometric studies
      that have generally but not always found correlations between lead exposures in
      childhood and some types of crime 20 years later; a small number of
      epidemiological studies that have found a dose-response relationship between lead
      exposure in childhood and self-reported and officially recorded criminal offences
      in young adulthood; and evidence for the biological plausibility of a causal
      relationship. Lead exposure in childhood may have played a small role in rising
      and falling crime rates in the USA but it is unlikely to account for the very
      high percentage of the decline suggested by the ecological studies. The major
      anomaly in the evidence is that the associations reported in ecological studies
      are much stronger (explaining 56-90% of the variation in crime rates) than the
      weaker relationships found in the cohort studies (that typically explain less
      than 1% of the variance in offending).  Suggestions are made for research that
      will better assess the contribution that reduced lead exposure has made to
      declining crime rates in the USA. 

PMID- 24555080
TI  - The parietal cell gastric H, K-ATPase also functions as the Na, K-ATPase and Ca
      ATPase in altered states.
AB  - This article offers an explanation for the apparent lack of Na, K-ATPase activity
      in parietal cells although ouabain has been known to inhibit gastric acid
      secretion since 1962. The gastric H, K-ATPase (proton-pump) seems to be acting in
      altered states, thus behaving like a Na, K-ATPase (Na-pump) and/or Ca-ATPase (Ca
      pump) depending on cellular needs.  This conclusion is based on the following
      findings. First, parietal cell fractions do not exhibit Na, K-ATPase activity at
      pH 7.0 but do at pH 8.5. Second, the apical plasma membrane (APM) fraction
      exhibits a (Ca or Mg)-ATPase activity with negligible H, K-ATPase activity.
      However, when assayed with Mg alone in presence of the 80 k Da cytosolic proton
      pump activator (HAF), the APM fraction reveals remarkably high H, K-ATPase
      activity, suggesting the observed low affinity of Ca (or Mg)-ATPase is an altered
      state of the latter. Third, calcium (between 1 and 4 uM) shows both stimulation
      and inhibition of the HAF-stimulated H, K-ATPase depending on its concentration,
      revealing a close interaction between the  proton-pump activator and local Ca
      concentration in gastric H, K-ATPase function. Such interactions suggest that Ca
      is acting as a terminal member of the intracellular signaling system for the HAF
      regulated proton-pump. It appears that during resting state, the HAF-associated
      H, K-ATPase remains inhibited by Ca (>1 uM) and, prior to resumption of acid
      secretion the gastric H, K-ATPase acts temporarily as a Ca-pump for removing
      excess Ca from its immediate environment. This conclusion is consistent with the
      recent reports of immunochemical co-localization of the gastric H, K-ATPase and
      Ca-ATPase by superimposition in parietal cells, and a transitory efflux of Ca
      immediately preceding the onset of acid secretion. These new perspectives on
      proton-pump function would open new avenues for a fuller understanding of the
      intracellular regulation of the ubiquitous Na-pump. 

PMID- 24555075
TI  - The nociceptive withdrawal reflex does not adapt to joint position change and
      short-term motor practice.
AB  - The nociceptive withdrawal reflex is a protective mechanism to mediate
      interactions within a potentially dangerous environment. The reflex is formed by
      action-based sensory encoding during the early post-natal developmental period,
      and it is unknown if the protective motor function of the nociceptive withdrawal
      reflex in the human upper-limb is adaptable based on the configuration of the arm
      or if it can be modified by short-term practice of a similar or opposing motor
      action. In the present study, nociceptive withdrawal reflexes were evoked by a
      brief train of electrical stimuli applied to digit II, 1) in five different
      static arm positions and, 2) before and after motor practice that was opposite
      (EXT) or similar (FLEX) to the stereotyped withdrawal response, in 10
      individuals. Withdrawal responses were quantified by the electromyography (EMG)
      reflex response in several upper limb muscles, and by the forces and moments
      recorded at the wrist. EMG onset latencies and response amplitudes were not
      significantly different across the arm positions or between the EXT and FLEX
      practice conditions, and the general direction of the withdrawal response was
      similar across arm positions. In addition, the force vectors were not different
      after practice in either the practice condition or between EXT and FLEX
      conditions. We conclude the withdrawal response is insensitive to changes in
      elbow or shoulder joint angles as well as remaining resistant to short-term
      adaptations from the practice of motor actions, resulting in a generalized limb
      withdrawal in each case. It is further hypothesized that the multisensory
      feedback is weighted differently in each arm position, but integrated to achieve
      a similar withdrawal response to safeguard against erroneous motor responses that
      could cause further harm. The results remain consistent with the concept that
      nociceptive withdrawal reflexes are shaped through long-term and not short-term
      action based sensory encoding. 

PMID- 24555085
TI  - Regulation of CYP3A genes by glucocorticoids in human lung cells.
AB  - Inhaled glucocorticoids are the first-line treatment for patients with persistent
      asthma.  However, approximately thirty percent of patients exhibit glucocorticoid
      insensitivity, which may involve excess metabolic clearance of the
      glucocorticoids by CYP3A enzymes in the lung.  CYP3A4, 3A5, and 3A7 enzymes
      metabolize glucocorticoids, which in turn induce CYP3A genes.  However, the
      mechanism of CYP3A5 mRNA regulation by glucocorticoids in lung cells has not been
      determined.  In hepatocytes, glucocorticoids bind to the glucocorticoid receptor
      (GR), which induces the expression of the constitutive androstane receptor or
      pregnane X receptor; both of which bind to the retinoid X receptor alpha, leading
      to the induction of CYP3A4, 3A5, and 3A7.  There is also evidence to suggest a
      direct induction of CYP3A5 by GR activation in liver cells. In this study, these
      pathways were evaluated as the mechanism for CYP3A5 mRNA induction by
      glucocorticoids in freshly isolated primary tracheal epithelial, adenocarcinomic
      human alveolar basal epithelial (A549), immortalized bronchial epithelial (BEAS
      2B), primary normal human bronchial/tracheal epithelial (NHBE), primary small
      airway epithelial (SAEC), and primary lobar epithelial lung cells. In A549 cells,
      beclomethasone 17-monopropionate ([M1]) induced CYP3A5 mRNA through the
      glucocorticoid receptor. CYP3A5 mRNA induction by five different glucocorticoids
      was attenuated by inhibiting the glucocorticoid receptor using ketoconazole, and
      for beclomethasone dipropionate, using siRNA-mediated knock-down of the
      glucocorticoid receptor. The constitutive androstane receptor was not expressed
      in lung cells. SAEC cells, a primary lung cell line, expressed CYP3A5, but CYP3A5
      mRNA was not induced by glucocorticoid treatment despite evaluating a multitude
      of cell culture conditions. None of the other lung cells expressed CYP3A4, 3A5 or
      3A7 mRNA. These studies demonstrate that CYP3A5 mRNA is induced by
      glucocorticoids in A549 cells via the glucocorticoid receptor, but that
      additional undefined regulatory processes exist in primary lung cells. 

PMID- 24555083
TI  - The effect of MEP pathway and other inhibitors on the intracellular localization
      of a plasma membrane-targeted, isoprenylable GFP reporter protein in tobacco BY-2
      cells.
AB  - We have established an in vivo visualization system for the geranylgeranylation
      of proteins in a stably transformed tobacco BY-2 cell line, based on the
      expression of a dexamethasone-inducible GFP fused to the carboxy-terminal basic
      domain of the rice calmodulin CaM61, which naturally bears a CaaL
      geranylgeranylation motif (GFP-BD-CVIL). By using pathway-specific inhibitors it
      was demonstrated that inhibition of the methylerythritol phosphate (MEP) pathway
      with known inhibitors like oxoclomazone and fosmidomycin, as well as inhibition
      of the protein geranylgeranyltransferase type 1 (PGGT-1), shifted the
      localization of the GFP-BD-CVIL protein from the membrane to the nucleus. In
      contrast, the inhibition of the mevalonate (MVA) pathway with mevinolin did not
      affect the localization. During the present work, this test system has been used
      to examine the effect of newly designed inhibitors of the MEP pathway and
      inhibitors of sterol biosynthesis such as squalestatin, terbinafine and Ro48
      8071. In addition, we also studied the impact of different post-prenylation
      inhibitors or those suspected to affect the transport of proteins to the plasma
      membrane on the localization of the geranylgeranylable fusion protein GFP-BD
      CVIL. 

PMID- 24555087
TI  - TNF-alpha neutralizing antibody blocks thermal sensitivity induced by compound
      48/80-provoked mast cell degranulation.
AB  - BACKGROUND: Neuro-inflammatory circuits in the tissue regulate the complex
      pathophysiology of pain. Protective nociceptive pain serves as an early warning
      system against noxious environmental stimuli. Tissue-resident mast cells
      orchestrate the increased thermal sensitivity following injection of basic
      secretagogue compound 48/80 in the hind paw tissues of ND4 mice. Here we
      investigated the effects of pre-treatment with TNF-alpha neutralizing antibody on
      compound 48/80-provoked thermal hyperalgesia. METHODS: We treated ND4 Swiss male
      mice with intravenous anti-TNF-alpha antibody or vehicle 30 minutes prior to
      bilateral, intra-plantar compound 48/80 administration and measured changes in
      the timing of hind paw withdrawal observed subsequent to mice being placed on a
      51oC hotplate. We also assessed changes in tissue swelling, TNF-alpha gene
      expression and protein abundance, mast cell degranulation, and neutrophil influx
      in the hind paw tissue. FINDINGS: We found that TNF-alpha neutralization
      significantly blocked thermal hyperalgesia, and reduced early tissue swelling.
      TNF-alpha neutralization had no significant effect on mast cell degranulation or
      neutrophil influx into the tissue, however. Moreover, no changes in TNF-alpha
      protein or mRNA levels were detected within 3 hours of administration of compound
      48/80. INTERPRETATION:   The neutralizing antibodies likely target pre-formed TNF
      alpha including that stored in the granules of tissue-resident mast cells. Pre
      formed TNF-alpha, released upon degranulation, has immediate effects on
      nociceptive signaling prior to the induction of neutrophil influx. These early
      effects on nociceptors are abrogated by TNF-alpha blockade, resulting in
      compromised nociceptive withdrawal responses to acute, harmful environmental
      stimuli.

PMID- 24555089
TI  - Thousands of exon skipping events differentiate among splicing patterns in
      sixteen human tissues.
AB  - Alternative splicing is widely recognized for its roles in regulating genes and
      creating gene diversity. However, despite many efforts, the repertoire of gene
      splicing variation is still incompletely characterized, even in humans. Here we
      describe a new computational system, ASprofile, and its application to RNA-seq
      data from Illumina's Human Body Map project (>2.5 billion reads).  Using the
      system, we identified putative alternative splicing events in 16 different human
      tissues, which provide a dynamic picture of splicing variation across the
      tissues. We detected 26,989 potential exon skipping events representing
      differences in splicing patterns among the tissues. A large proportion of the
      events (>60%) were novel, involving new exons (~3000), new introns (~16000), or
      both. When tracing these events across the sixteen tissues, only a small number
      (4-7%) appeared to be differentially expressed ('switched') between two tissues,
      while 30-45% showed little variation, and the remaining 50-65% were not present
      in one or both tissues compared.  Novel exon skipping events appeared to be
      slightly less variable than known events, but were more tissue-specific. Our
      study represents the first effort to build a comprehensive catalog of alternative
      splicing in normal human tissues from RNA-seq data, while providing insights into
      the role of alternative splicing in shaping tissue transcriptome differences. The
      catalog of events and the ASprofile software are freely available from the Zenodo
      repository ( http://zenodo.org/record/7068; doi: 10.5281/zenodo.7068) and from
      our web site http://ccb.jhu.edu/software/ASprofile. 

PMID- 24555090
TI  - Delayed intra-abdominal bleeding following trans-vaginal ultrasonography guided
      oocyte retrieval for in vitro fertilization in patients at risk for thrombo
      embolic events under anticoagulant therapy.
AB  - We report herein, two cases of massive delayed (2 and 4 days) intra abdominal
      hemorrhage following ovum pick-up (OPU), in patients at risk for thrombo-embolic
      events, who concomitantly used therapeutic doses of low molecular weight heparin
      (LMWH). We discuss the possible mechanisms involved in causing the aforementioned
      delayed bleeding, and call for re-evaluation of the presently accepted
      anticoagulant co-treatment regimen. These case reports should direct physicians'
      attention and keep them alert, while conducting IVF treatment to this subgroup of
      high risk patients. 

PMID- 24555091
TI  - taxize: taxonomic search and retrieval in R.
AB  - All species are hierarchically related to one another, and we use taxonomic names
      to label the nodes in this hierarchy. Taxonomic data is becoming increasingly
      available on the web, but scientists need a way to access it in a programmatic
      fashion that's easy and reproducible. We have developed taxize, an open-source
      software package (freely available from http://cran.r
      project.org/web/packages/taxize/index.html) for the R language. taxize provides
      simple, programmatic access to taxonomic data for 13 data sources around the web.
      We discuss the need for a taxonomic toolbelt in R, and outline a suite of use
      cases for which taxize is ideally suited (including a full workflow as an
      appendix). The taxize package facilitates open and reproducible science by
      allowing taxonomic data collection to be done in the open-source R platform. 

PMID- 24555092
TI  - Kairomonal communication in mice is concentration-dependent with a proportional
      discrimination threshold.
AB  - Odors of predators are often co-opted by prey species to serve as warning
      signals. Perceptual properties of such kairomonal communication are under studied
      despite their common use in many mammals. We demonstrate that the kairomonal
      response in mice to rat odors varies monotonically with the volume of rat odor.
      Moreover, the ability of mice to differentiate between two strengths of rat odors
      is dependent on the ratio of the two concentrations. These results show that mice
      can compare kairomonal strength over a large range of values, and that kairomonal
      communication follows Weber's law. 

PMID- 24555099
TI  - Homologous electron transport components fail to increase fatty acid
      hydroxylation in transgenic Arabidopsis thaliana.
AB  - Ricinoleic acid, a hydroxylated fatty acid (HFA) present in castor ( Ricinus
      communis) seeds, is an important industrial commodity used in products ranging
      from inks and paints to polymers and fuels. However, due to the deadly toxin
      ricin and allergens also present in castor, it would be advantageous to produce
      ricinoleic acid in a different agricultural crop. Unfortunately, repeated efforts
      at heterologous expression of the castor fatty acid hydroxylase (RcFAH12) in the
      model plant Arabidopsis thaliana have produced only 17-19% HFA in the seed
      triacylglycerols (TAG), whereas castor seeds accumulate up to 90% ricinoleic acid
      in the endosperm TAG. RcFAH12 requires an electron supply from NADH:cytochrome b5
      reductase (CBR1) and cytochrome b5 (Cb5) to synthesize ricinoleic acid.
      Previously, our laboratory found a mutation in the Arabidopsis CBR1 gene, cbr1-1,
      that caused an 85% decrease in HFA levels in the RcFAH12 Arabidopsis line. These
      results raise the possibility that electron supply to the heterologous RcFAH12
      may limit the production of HFA. Therefore, we hypothesized that by
      heterologously expressing RcCb5, the reductant supply to RcFAH12 would be
      improved and lead to increased HFA accumulation in Arabidopsis seeds. Contrary to
      this proposal, heterologous expression of the top three RcCb5 candidates did not
      increase HFA accumulation. Furthermore, coexpression of RcCBR1 and RcCb5 in
      RcFAH12 Arabidopsis also did not increase in HFA levels compared to the parental
      lines. These results demonstrate that the Arabidopsis electron transfer system is
      supplying sufficient reductant to RcFAH12 and that there must be other
      bottlenecks limiting the accumulation of HFA. 

PMID- 24555102
TI  - A computational analysis of the long-term regulation of arterial pressure.
AB  - The asserted dominant role of the kidneys in the chronic regulation of blood
      pressure and in the etiology of hypertension has been debated since the 1970s. At
      the center of the theory is the observation that the acute relationships between
      arterial pressure and urine production-the acute pressure-diuresis and pressure
      natriuresis curves-physiologically adapt to perturbations in pressure and/or
      changes in the rate of salt and volume intake. These adaptations, modulated by
      various interacting neurohumoral mechanisms, result in chronic relationships
      between water and salt excretion and pressure that are much steeper than the
      acute relationships. While the view that renal function is the dominant
      controller of arterial pressure has been supported by computer models of the
      cardiovascular system known as the "Guyton-Coleman model", no unambiguous
      description of a computer model capturing chronic adaptation of acute renal
      function in blood pressure control has been presented. Here, such a model is
      developed with the goals of: 1. representing the relevant mechanisms in an
      identifiable mathematical model; 2. identifying model parameters using
      appropriate data; 3. validating model predictions in comparison to data; and 4.
      probing hypotheses regarding the long-term control of arterial pressure and the
      etiology of primary hypertension. The developed model reveals: long-term control
      of arterial blood pressure is primarily through the baroreflex arc and the renin
      angiotensin system; and arterial stiffening provides a sufficient explanation for
      the etiology of primary hypertension associated with ageing. Furthermore, the
      model provides the first consistent explanation of the physiological response to
      chronic stimulation of the baroreflex. 

PMID- 24555103
TI  - Protein structure quality assessment based on the distance profiles of
      consecutive backbone Calpha atoms.
AB  - Predicting the three dimensional native state structure of a protein from its
      primary sequence is an unsolved grand challenge in molecular biology. Two main
      computational approaches have evolved to obtain the structure from the protein
      sequence - ab initio/de novo methods and template-based modeling - both of which
      typically generate multiple possible native state structures. Model quality
      assessment programs (MQAP) validate these predicted structures in order to
      identify the correct native state structure. Here, we propose a MQAP for
      assessing the quality of protein structures based on the distances of consecutive
      Calpha atoms. We hypothesize that the root-mean-square deviation of the distance
      of consecutive Calpha (RDCC) atoms from the ideal value of 3.8 A, derived from a
      statistical analysis of high quality protein structures (top100H database), is
      minimized in native structures. Based on tests with the top100H set, we propose a
      RDCC cutoff value of 0.012 A, above which a structure can be filtered out as a
      non-native structure. We applied the RDCC discriminator on decoy sets from the
      Decoys 'R' Us database to show that the native structures in all decoy sets
      tested have RDCC below the 0.012 A cutoff. While most decoy sets were either
      indistinguishable using this discriminator or had very few violations, all the
      decoy structures in the fisa decoy set were discriminated by applying the RDCC
      criterion. This highlights the physical non-viability of the fisa decoy set, and
      possible issues in benchmarking other methods using this set. The source code and
      manual is made available at https://github.com/sanchak/mqap and permanently
      available on 10.5281/zenodo.7134. 

PMID- 24555103
TI  - Protein structure quality assessment based on the distance profiles of
      consecutive backbone Calpha atoms.
AB  - Predicting the three dimensional native state structure of a protein from its
      primary sequence is an unsolved grand challenge in molecular biology. Two main
      computational approaches have evolved to obtain the structure from the protein
      sequence - ab initio/de novo methods and template-based modeling - both of which
      typically generate multiple possible native state structures. Model quality
      assessment programs (MQAP) validate these predicted structures in order to
      identify the correct native state structure. Here, we propose a MQAP for
      assessing the quality of protein structures based on the distances of consecutive
      Calpha atoms. We hypothesize that the root-mean-square deviation of the distance
      of consecutive Calpha (RDCC) atoms from the ideal value of 3.8 A, derived from a
      statistical analysis of high quality protein structures (top100H database), is
      minimized in native structures. Based on tests with the top100H set, we propose a
      RDCC cutoff value of 0.012 A, above which a structure can be filtered out as a
      non-native structure. We applied the RDCC discriminator on decoy sets from the
      Decoys 'R' Us database to show that the native structures in all decoy sets
      tested have RDCC below the 0.012 A cutoff. While most decoy sets were either
      indistinguishable using this discriminator or had very few violations, all the
      decoy structures in the fisa decoy set were discriminated by applying the RDCC
      criterion. This highlights the physical non-viability of the fisa decoy set, and
      possible issues in benchmarking other methods using this set. The source code and
      manual is made available at https://github.com/sanchak/mqap and permanently
      available on 10.5281/zenodo.7134. 

PMID- 24555105
TI  - Does excitatory fronto-extracerebral tDCS lead to improved working memory
      performance?
AB  - Evidence suggests that excitatory transcranial direct current stimulation (tDCS)
      may improve performance on a wide variety of cognitive tasks. Due to the non
      invasive and inexpensive nature of the method, harnessing its potential could be
      particularly useful for the treatment of neuropsychiatric illnesses involving
      cognitive dysfunction. However, questions remain regarding the efficacious
      stimulation parameters. Here, using a double-blind between-subjects design, we
      explored whether 1 mA excitatory (anodal) left dorsolateral prefrontal cortex
      stimulation with a contralateral extracerebral reference electrode, leads to
      enhanced working memory performance across two days, relative to sham
      stimulation. Participants performed the 3-back, a test of working memory, at
      baseline, and during and immediately following stimulation on two days, separated
      by 24-48 hours. Active stimulation did not significantly enhance performance
      versus sham over the course of the experiment. However, exploratory comparisons
      did reveal a significant effect of stimulation group on performance during the
      first stimulation phase only, with active stimulation recipients performing
      better than sham. While these results do not support the hypothesis that
      dorsolateral prefrontal cortex tDCS boosts working memory, they raise the
      possibility that its effects may be greatest during early learning stages. 

PMID- 24555108
TI  - ANGDelMut - a web-based tool for predicting and analyzing functional loss
      mechanisms of amyotrophic lateral sclerosis-associated angiogenin mutations.
AB  - ANGDelMut is a web-based tool for predicting the functional consequences of
      missense mutations in the angiogenin (ANG) protein, which is associated with
      amyotrophic lateral sclerosis (ALS). Missense mutations in ANG result in loss of
      either ribonucleolytic activity or nuclear translocation activity or both of
      these functions, and in turn cause ALS. However, no web-based tools are available
      to predict whether a newly identified ANG mutation will possibly lead to ALS.
      More importantly, no web-implemented method is currently available to predict the
      mechanisms of loss-of-function(s) of ANG mutants. In light of this observation,
      we developed the ANGDelMut web-based tool, which predicts whether an ANG mutation
      is deleterious or benign. The user selects certain attributes from the input
      panel, which serves as a query to infer whether a mutant will exhibit loss of
      ribonucleolytic activity or nuclear translocation activity or whether the overall
      stability will be affected. The output states whether the mutation is deleterious
      or benign, and if it is deleterious, gives the possible mechanism(s) of loss-of
      function. This web-based tool, freely available at
      http://bioschool.iitd.ernet.in/DelMut/, is the first of its kind to provide a
      platform for researchers and clinicians, to infer the functional consequences of
      ANG mutations and correlate their possible association with ALS ahead of
      experimental findings. 

PMID- 24555112
TI  - Severe bilateral amyotrophic neuralgia associated with major dysphagia secondary
      to acute hepatitis E.
AB  - INTRODUCTION: Several acute neurological syndromes can be triggered by immune
      events. Hepatitis E virus (HEV), an emerging infectious disease, can be one of
      these triggers. CASE REPORT: We report the case of a 36-year-old man that
      presented nausea and a dull abdominal pain for a week and then felt an acute
      neuralgic pain involving both shoulders that lasted for 8 to 10 hours.
      Immediately after, the patient presented a severe bilateral muscular weakness of
      the proximal part of both upper limbs, corresponding to an amyotrophic neuralgia.
      Two days after the shoulder pain, the patient presented a dysphagia necessitating
      tube feeding.  A blood sample confirmed hepatitis caused by hepatitis E virus
      (HEV; genotype 3F). Oral feeding resumed progressively after five months. The
      patient was fully independent for the activities of daily living but was still
      unable to work after six months. CONCLUSION: Amyotrophic neuralgia and hepatitis
      E are both under-diagnosed. It is noteworthy that HEV can trigger amyotrophic
      neuralgia. Antiviral drugs, oral steroids and intravenous immunoglobulins can be
      proposed, but the optimal treatment has  not yet been determined.

PMID- 24555115
TI  - Cladonia lichens on extensive green roofs: evapotranspiration, substrate
      temperature, and albedo.
AB  - Green roofs are constructed ecosystems that provide ecosystem services in urban
      environments. Shallow substrate green roofs subject the vegetation layer to
      desiccation and other environmental extremes, so researchers have evaluated a
      variety of stress-tolerant vegetation types for green roof applications. Lichens
      can be found in most terrestrial habitats.  They are able to survive extremely
      harsh conditions, including frequent cycles of desiccation and rehydration,
      nutrient-poor soil, fluctuating temperatures, and high UV intensities. Extensive
      green roofs (substrate depth <20cm) exhibit these harsh conditions, making
      lichens possible candidates for incorporation into the vegetation layer on
      extensive green roofs.  In a modular green roof system, we tested the effect of
      Cladonia lichens on substrate temperature, water loss, and albedo compared to a
      substrate-only control. Overall, the Cladonia modules had significantly cooler
      substrate temperatures during the summer and significantly warmer temperatures
      during the fall.  Additionally, the Cladonia modules lost significantly less
      water than the substrate-only control. This implies that they may be able to
      benefit neighboring vascular plant species by reducing water loss and maintaining
      favorable substrate temperatures. 

PMID- 24563775
TI  - Computed tomography coronary angiography: Is radiation a concern for the gold
      standard test for anomalous coronary arteries?
AB  - Multi-detector computed tomography is now an established modality for the
      investigation of coronary artery disease.1,2^ 64-Slice multi-detector computed
      tomography is the standard requirement by the British society of cardiac imaging
      and can image the whole heart in four heart beats. The 320 slice multi-detector
      computed tomography can image the heart in one heart beat, but both technologies
      depend on B-blockers to slow the patient's heart rate to 60 beats per minute to
      ensure excellent image quality and low radiation dose. The faster dual source
      multi-detector computed tomography is less dependent on B-blockers. The
      availability and ease of use of multi-detector computed tomography has meant that
      it is increasingly used in younger patients to rule out coronary artery disease
      or rule out anomalous coronary arteries. We consider the radiation associated
      with computed tomography coronary angiography and the available dose reduction
      techniques. 

PMID- 24563776
TI  - Detecting Pyronin Y labeled RNA transcripts in live cell microenvironments by
      phasor-FLIM analysis.
AB  - Pyronin Y is an environment-sensitive probe which labels all double-stranded RNA
      in live cells. Methods to determine which RNA species Pyronin Y may be labeling
      are limited due to the lack of studies aimed at determining whether this probe
      has different spectroscopic properties when bound to specific transcripts. A
      major issue is that transcripts are difficult to isolate and study individually.
      We detected transcripts directly in their biological environment allowing us to
      identify RNA species on the basis of their location in the cell. We show that the
      phasor approach to lifetime analysis has the sensitivity to determine at least
      six different RNA species in live fibroblast cells. The detected lifetime
      differences were consistent among cells. To our knowledge this is the first
      application of a spectroscopic technique aimed at identifying Pyronin Y labeled
      RNA subtypes in living cells.

PMID- 24563777
TI  - Awareness of, responsiveness to and practice of patients' rights at Uganda's
      national referral hospital.
AB  - BACKGROUND: The realisation of patients' rights in resource-constrained and
      patient-burdened public health care settings in Uganda remains an obstacle
      towards quality health care delivery, health care-seeking behaviour and health
      outcomes. Although the Uganda Patients' Charter of 2009 empowers patients to
      demand quality care, inequitable access and abuse remain common. AIM: The study
      aimed to assess level of awareness of, responsiveness to and practice of
      patients' rights amongst patients and health workers (HWs) at Uganda's national
      referral hospital, Mulago Hospital in Kampala. METHODS: A three-phase cross
      sectional questionnaire-based descriptive survey was conducted amongst 211
      patients, 98 HWs and 16 key informants using qualitative and quantitative data
      collection methods. The study was conducted in May-June 2012, 2.5 years after the
      launch of the Uganda Patients' Charter. RESULTS: At least 36.5% of patients faced
      a challenge regarding their rights whilst seeking health care. Most of the
      patients (79%) who met a challenge never attempted to demand their rights. Most
      patients (81.5%) and HWs (69.4%) had never heard of the Uganda Patients' Charter.
      Awareness of patients' rights was significantly higher amongst HWs (70%) than
      patients (40%) (p < 0.01). Patients' awareness was associated with education
      level (chi2 = 42.4, p < 0.001), employment status (chi2 = 33.6, p < 0.001) and
      hospital visits (chi2 = 3.9, p = 0.048). For HWs it was associated with education
      level (chi2 = 155.6, p < 0.001) and length of service (chi2 = 154.5, p <0.001).
      Patients feel powerless to negotiate for their rights and fear being
      discriminated against based on their ability to bribe HWs with money to access
      care, and political, socio-economic and tribal status. CONCLUSION AND
      RECOMMENDATIONS: Awareness of, responsiveness to and practice of patients' rights
      remains limited at Mulago Hospital. There is a need for urgent implementation of
      an integrated multilevel, multichannel, patient-centred approach that
      incorporates social services and addresses intrinsic patient, HW and health
      system factors to strengthen patients' rights issues at the hospital.

PMID- 24563779
TI  - Assessing the Health Impact of the following Measures in Schools in Maradi
      (Niger): Construction of Latrines, Clean Water Supply, Establishment of Hand
      Washing Stations, and Health Education.
AB  - Objective. To assess the effect on health of the following measures in schools in
      Maradi (Niger): clean water supply, construction of latrines, establishment of
      hand washing stations, and health education. Methodology. It was a "before and
      after" intervention study on a sample of school children aged 7 to 12 years in
      the Maradi region. The interventions included building of latrines, supplying
      clean water, setting up hand washing stations, and teaching health education
      lessons. An individual questionnaire, analysis of stool samples, and a group
      questionnaire were administered to children and teachers, respectively. The
      threshold for significance was set at P < 0.05. Results. A statistically
      significant reduction in cases of diarrhoea and abdominal pains was noted after
      the project. Overall, carriage of at least one parasite increased from 7.5%
      before the project to 10.2% after it (P = 0.04). In the programme group schools,
      there was a statistically significant increase in the prevalence of Hymenolepis
      nana, from 0 to 1.9 (P = 0.02). Pinworm prevalence remained stable in this group
      but increased significantly in the control group. Conclusions. Putting health
      infrastructure in place in schools obviously had an impact on hygiene-related
      habits in the beneficiary schools and communities. 

PMID- 24563778
TI  - Sensing of EGTA Mediated Barrier Tissue Disruption with an Organic Transistor.
AB  - Barrier tissue protects the body against external factors by restricting the
      passage of molecules. The gastrointestinal epithelium is an example of barrier
      tissue with the primary purpose of allowing the passage of ions and nutrients,
      while restricting the passage of pathogens and toxins. It is well known that the
      loss of barrier function can be instigated by a decrease in extracellular calcium
      levels, leading to changes in protein conformation and an increase in
      paracellular transport. In this study, ethylene glycol-bis(beta-aminoethyl ether)
      N,N,N',N'-tetra acetic acid (EGTA), a calcium chelator, was used to disrupt the
      gastrointestinal epithelial barrier. The effect of EGTA on barrier tissue was
      monitored by a novel label-free method based on an organic electrochemical
      transistor (OECT) integrated with living cells and validated against conventional
      methods for measuring barrier tissue integrity. We demonstrate that the OECT can
      detect breaches in barrier tissue upon exposure to EGTA with the same sensitivity
      as existing methods but with increased temporal resolution. Due to the potential
      of low cost processing techniques and the flexibility in design associated with
      organic electronics, the OECT has great potential for high-throughput, disposable
      sensing and diagnostics. 

PMID- 24563780
TI  - Prevalence survey of selected bovine pathogens in water buffaloes in the north
      region of Brazil.
AB  - Although the largest buffalo herd in the occident is in the north region of
      Brazil, few studies have been conducted to assess the prevalence of selected
      parasitic diseases in buffalo herd. The present study was therefore conducted to
      investigate the epidemiological of Toxoplasma gondii, Neospora caninum, Anaplasma
      marginale, Babesia bigemina, and Babesia bovis in water buffaloes in the north
      region of Brazil. A total of 4796 buffalo blood samples were randomly collected
      from five provinces and simultaneously analyzed by the IFAT and ELISA. The
      serological prevalence of T. gondii and N. caninum was 41.3% and 55.5% in ELISA
      and 35.7% and 48.8% in IFAT, respectively. The overall prevalence of A.
      marginale, B. bovis, and B. bigemina was 63%, 25%, and 21% by ELISA and 50.0%,
      22.5%, and 18.8% by IFAT, respectively. This study shows valuable information
      regarding the serological survey of selected bovine pathogens in water buffaloes
      in the north region of Brazil which will likely be very beneficial for the
      management and control programs of this disease. 

PMID- 24563781
TI  - Does duloxetine improve cognitive function independently of its antidepressant
      effect in patients with major depressive disorder and subjective reports of
      cognitive dysfunction?
AB  - Introduction. Cognitive deficits are commonly reported by patients with major
      depressive disorder (MDD). Duloxetine, a dual serotonin/noradrenaline reuptake
      inhibitor, may improve cognitive deficits in MDD. It is unclear if cognitive
      improvements occur independently of antidepressant effects with standard
      antidepressant medications. Methods. Thirty participants with MDD who endorsed
      cognitive deficits at screening received 12-week duloxetine treatment. Twenty-one
      participants completed treatment and baseline and posttreatment cognitive
      testing. The Cambridge Neuropsychological Test Automated Battery was used to
      assess the following cognitive domains: attention, visual memory, executive
      function/set shifting and working memory, executive function/spatial planning,
      decision making and response control, and verbal learning and memory. Results.
      Completers showed significant cognitive improvements across several domains on
      tasks assessing psychomotor function and mental processing speed, with additional
      improvements in visual and verbal learning and memory, and affective decision
      making and response control. Overall significance tests for executive function
      tasks were also significant, although individual tasks were not, perhaps due to
      the small sample size. Most notably, cognitive improvements were observed
      independently of symptom reduction on all domains except verbal learning and
      memory. Conclusions. Patients reporting baseline cognitive deficits achieved
      cognitive improvements with duloxetine treatment, most of which were independent
      of symptomatic improvement. This trial is registered with NCT00933439. 

PMID- 24563782
TI  - Improved outcomes with intensity modulated radiation therapy combined with
      temozolomide for newly diagnosed glioblastoma multiforme.
AB  - Purpose. Glioblastoma multiforme (GBM) is optimally treated by maximal debulking
      followed by combined chemoradiation. Intensity modulated radiation therapy (IMRT)
      is gaining widespread acceptance in other tumour sites, although evidence to
      support its use over three-dimensional conformal radiation therapy (3DCRT) in the
      treatment of gliomas is currently lacking. We examined the survival outcomes for
      patients with GBM treated with IMRT and Temozolomide. Methods and Materials. In
      all, 31 patients with GBM were treated with IMRT and 23 of these received
      chemoradiation with Temozolomide. We correlated survival outcomes with patient
      functional status, extent of surgery, radiation dose, and use of chemotherapy.
      Results. Median survival for all patients was 11.3 months, with a median survival
      of 7.2 months for patients receiving 40.05 Gray (Gy) and a median survival of
      17.4 months for patients receiving 60 Gy. Conclusions. We report one of the few
      series of IMRT in patients with GBM. In our group, median survival for those
      receiving 60 Gy with Temozolomide compared favourably to the combined therapy arm
      of the largest randomised trial of chemoradiation versus radiation to date (17.4
      months versus 14.6 months). We propose that IMRT should be considered as an
      alternative to 3DCRT for patients with GBM. 

PMID- 24563783
TI  - Values of Alpha 1 Microglobulin Does Not Differ between Individuals with and
      without Family History of Balkan Endemic Nephropathy.
AB  - Aim. The aim of this study was to compare urinary alpha 1 microglobulin (A1MG) in
      healthy individuals with and without family burden for Balkan endemic nephropathy
      (BEN) in an endemic village. Methods. Otherwise healthy inhabitants with
      microalbuminuria or proteinuria were divided into two groups: with (n = 24) and
      without (n = 32) family BEN burden and screened for urinary A1MG and A1MG/urine
      creatinine ratio. Results. Average value of urinary A1MG was 10.35 +/- 7.01 mg/L
      in group with and 10.79 +/- 8.27 mg/L in group without family history for BEN
      (NS, P = 0.87). A1MG was higher than 10 mg/L in eight (33.33%) inhabitants with
      family history and in 12 (37.5%) without (NS, P = 0.187). Average values of
      urinary A1MG/creatinine ratio were 1.30 +/- 1.59 and 0.94 +/- 0.78 in group with
      and group without family BEN history (NS, P = 0.39, resp.). Elevated values of
      this ratio were found in 13 (54.17%) inhabitants with and 14 (43.75%) without
      family history for BEN (NS, P = 0.415). Conclusion. We did not find statistically
      significant difference in the examined markers between healthy individuals with
      and without family burden for BEN. We concluded that these markers are not
      predictive of risk for BEN. 

PMID- 24563784
TI  - A Comparison between Emergency Medicine Residency Training Programs in the United
      States and Saudi Arabia from the Residents' Perception.
AB  - Objectives. This study was designed to compare the trainees' perception of
      emergency medicine (EM) training in the United States (US) and Saudi Arabia (SA)
      and to identify residents' levels of confidence and points of satisfaction in
      education, procedural skills, and work environment. Method. An IRB-exempt
      anonymous web-based survey was distributed to five EM residency training programs
      in the USA and three residency regions in SA. Results. 342 residents were polled
      with a 20% response rate (16.8% USA and 25.8% SA). The Saudi residents responded
      less positively to the questions about preparation for their boards'
      examinations, access to multiple educational resources, and weekly academic
      activities. The Saudi trainees felt less competent in less common procedures than
      US trainees. American trainees also more strongly agree that they have more
      faculty interest in their education compared to the Saudi trainees. The Saudi
      residents see more patients per hour compared to their US peers. Conclusion.
      These findings may be due to the differences in training techniques including
      less formal didactics and simulation experience in SA and more duty hour
      regulations in the USA. 

PMID- 24563785
TI  - Children's Mental Health Visits to the Emergency Department: Factors Affecting
      Wait Times and Length of Stay.
AB  - Objective. This study explores the association of patient and emergency
      department (ED) mental health visit characteristics with wait time and length of
      stay (LOS). Methods. We examined data from 580 ED mental health visits made to
      two urban EDs by children aged <=18 years from April 1, 2004, to March 31, 2006.
      Logistic regressions identified characteristics associated with wait time and LOS
      using hazard ratios (HR) with 95% confidence intervals (CIs). Results. Sex (male:
      HR = 1.48, 95% CI = 1.20-1.84), ED type (pediatric ED: HR = 5.91, 95% CI = 4.16
      8.39), and triage level (Canadian Triage and Acuity Scale (CTAS) 2: HR = 3.62,
      95% CI = 2.24-5.85) were statistically significant predictors of wait time. ED
      type (pediatric ED: HR = 1.71, 95% CI = 1.18-2.46), triage level (CTAS 5: HR =
      2.00, 95% CI = 1.15-3.48), number of consultations (HR = 0.46, 95% CI = 0.31
      0.69), and number of laboratory investigations (HR = 0.75, 95% CI = 0.66-0.85)
      predicted LOS. Conclusions. Based on our results, quality improvement initiatives
      to reduce ED waits and LOS for pediatric mental health visits may consider
      monitoring triage processes and the availability, access, and/or time to receipt
      of specialty consultations. 

PMID- 24563786
TI  - Primary synovial sarcomas of the mediastinum: a systematic review and pooled
      analysis of the published literature.
AB  - Background. The aim of this systematic review is to attempt to provide a
      descriptive analysis for cases of synovial sarcoma (SS) arising in the
      mediastinum and to analyze prognostic factors. Methods. We performed PubMed
      database search in July 2013. Twenty-two studies, which included 40 patients,
      form the basis of this review. Demographic and disease-related factors were
      analyzed for possible influence on survival. Findings were compared with
      extremity SS studies reported in literature. Results. Sixteen cases (40%)
      presented with locally advanced unresectable disease, 2 (5%) with metastatic
      disease, and 22 (55%) with localized resectable disease. Median tumor size was 11
      cm (range: 5-20 cm). Thirty patients were assessable for survival and had a 5
      year OS of 36%. Completeness of resection was the only factor associated with
      significant improvement in OS (5-year survival of 63% and 0% in favor of complete
      resection, P = 0.003). Conclusion. Mediastinal SS is associated with poor
      prognosis as more cases are diagnosed at an advanced stage and with larger tumor
      size compared to extremity SS. Complete surgical resection is the only identified
      factor associated with better prognosis and may result in survival outcomes that
      are comparable with those for localized SS of the extremity. 

PMID- 24563787
TI  - Association of reticular pseudodrusen and early onset drusen.
AB  - Purpose. To report an association between reticular pseudodrusen, located above
      the retinal pigment epithelium (RPE), and Early Onset Drusen (EOD) as described
      using Spectral-Domain Optical Coherence Tomography (SD-OCT). Methods. Eight
      patients (16 eyes) with EOD were examined. EOD were classified into three
      entities called Large Colloid Drusen (LCD), Malattia Leventinese (ML), and
      Cuticular Drusen (CD). Best-corrected visual acuity, fundus examination, color
      fundus photographs, fundus autofluorescence (FAF), fluorescein angiography (FA),
      indocyanine green angiography (ICGA), and SD-OCT were performed in all study
      patients. Results. Four patients had LCD, 2 had ML, and 2 had CD. Reticular
      pseudodrusen were observed with SD-OCT in all study patients; all these patients
      had hyperreflective lesions above and below the RPE. Conclusion. Early Onset
      Drusen appear to be associated with reticular pseudodrusen. SD-OCT is helpful in
      distinguishing the location of the deposits that are above and below the RPE in
      EOD. Further studies are needed to understand the role of reticular pseudodrusen
      in the pathophysiology of EOD. 

PMID- 24563788
TI  - Long-Term Followup of Laser In Situ Keratomileusis for Hyperopia Using a 213 nm
      Wavelength Solid-State Laser.
AB  - Purpose. To evaluate the long-term efficacy, accuracy, stability, and safety of
      hyperopic laser in situ keratomileusis (LASIK) using a 213 nm wavelength solid
      state laser. Methods. This prospective noncomparative case series consisted of 34
      eyes of 17 patients which underwent hyperopic LASIK using a 213 nm solid-state
      laser (Pulzar Z1, CustomVis) at an outpatient refractive surgery center in
      Manila, Philippines. The preoperative and postoperative examinations included
      uncorrected distance visual acuity (UDVA), subjective manifest refraction,
      corrected distance visual acuity (CDVA), cycloplegic refraction, slitlamp
      biomicroscopy, and keratometry (K). Main Outcome Measures. Accuracy, efficacy,
      stability, and safety of the refractive procedure. Results. Mean follow-up was
      25.18 +/- 13.79 months. At the end of follow-up, 26.47% had a UDVA of 20/20 and
      94.12% had a UDVA of >=20/40. Manifest refractive spherical equivalent (MRSE) was
      within +/-0.50 D of the target refraction in 55.88% and within +/-1.0 D in 85.30%
      of the study eyes. Refractive stability was noted in the 1st postoperative month
      while hyperopic regression was noted after the 3rd postoperative year. No eye
      lost more than 2 lines of CDVA. Conclusion. Our results show that the 213 nm
      solid state laser system is safe, effective, accurate, and predictable for the
      treatment of hyperopia. 

PMID- 24563790
TI  - Incidence of retinal detachment after fellow-performed primary pars plana
      vitrectomy.
AB  - Background. Primary pars plana vitrectomy (PPV) is often performed by
      vitreoretinal fellows. We aimed to evaluate the incidence of retinal breaks and
      detachments (RD) after fellow-performed PPV. Methods. We reviewed 119 consecutive
      cases of standard 3-port primary PPVs on 115 patients at a teaching institution
      from 2003 to 2006. In all cases, the primary surgeon was a vitreoretinal fellow.
      Patients with previous RD were excluded. Cases were reviewed for postoperative
      retinal detachments, and all patients were followed for up to 1 year. Results.
      Intraoperative retinal breaks occurred in 5 of 119 eyes (4.2%). One break was
      associated with sclerotomy and 4 were not. Postoperative RD occurred in 8 of 119
      eyes (6.7%). Two RDs were sclerotomy related, 5 were not, and 1 was of
      indeterminate origin. Conclusions. Incidence of retinal breaks and RD following
      primary PPV by vitreoretinal fellows is low and comparable to that of fellowship
      trained surgeons. 

PMID- 24563791
TI  - Subconjunctival bevacizumab injection in glaucoma filtering surgery: a case
      control series.
AB  - Aims. To describe the use of subconjunctival bevacizumab (SCB) injection in the
      combined cataract and glaucoma filtering surgery (GFS). Methods. Retrospective
      comparative case series. Thirty eyes of twenty-eight patients who had GFS
      followed by SCB injection as part of post-operative management were included
      (Group SCB). The types of GFS included trabeculectomy and non-penetrating
      glaucoma surgery (NPGS) with mitomycin-C. Outcome measures included the reduction
      of intraocular pressure (IOP) and medications. Age-matched patients who had the
      same types of surgery without SCB were selected as a control group (Group C).
      Results. The types of GFS were: combined cataract surgery and NPGS (SCB: 20; C:
      24), phacotrabeculectomy (SCB: 6; C: 3), NPGS (SCB: 3; C: 2) and trabeculectomy
      alone (SCB: 1; C: 1). The average follow-up time was 16.9 (+/-8.2) months in the
      SCB group and 19.6 (+/-11.5) months in the controls. 1.25 mg of bevacizumab was
      injected on average 14.1 (range: 3-42) days post-GFS. The mean IOP decreased from
      21.9 (+/-9.8) to 11.9 (+/-4.7) mmHg in the controls and from 19.6 (+/-8.9) to
      14.0 (+/-4.7) mmHg in the SCB group. There was no statistically significant
      difference between the two groups (P = 0.11). Complications included three cases
      of branch vein occlusion in the SCB group. Conclusions. SCB did not result in
      better outcome in term of IOP reduction. Clinicians should monitor its side
      effects in glaucoma patients. 

PMID- 24563792
TI  - Clinicopathological features of dacryolithiasis in Japanese patients: frequent
      association with infection in aged patients.
AB  - Purpose. The purpose of this study is to elucidate the clinicopathological
      features of dacryolithiasis and prevalence of associated infection in Japanese
      patients. Materials and Methods. Out of 13,471 outclinic patients from 2006 to
      2011, 268 patients were scheduled to be performed dacryocystorhinostomy (DCR) due
      to dacryocystitis with nasolacrimal duct obstruction. Actually 266 patients
      underwent dacryocystorhinostomy (DCR) and two patients were cured by only
      ophthalmic examination. Dacryoliths were found in 17 cases (6.3%). Among 17 cases
      of dacryolithiasis, three patients were male, and 14 were female. The age of the
      patients ranged from 32 to 82 (mean 67) years, and 13 cases (76%) were more than
      65 years of age. Pathological examination disclosed the infectious agents in 9
      cases (53%), and all patients with infection were more than 65 years of age.
      Special stains revealed colonies of fungus, suspicious of Aspergillus, in 6 cases
      and gram-positive rods, and suspicious of Actinomyces, in 3 cases. Conclusions.
      The current study showed the frequent association of infection with
      dacryolithiasis in aged Japanese patients. This should be taken into the
      consideration for the treatment of dacryolithiasis. 

PMID- 24563793
TI  - Preoperative and postoperative optical coherence tomography findings in patients
      with rhegmatogenous retinal detachment involving the macular region.
AB  - Purpose. To evaluate morphologic changes of the macula, we observed eyes with
      rhegmatogenous retinal detachment (RRD) involving the macular region by optical
      coherence tomography (OCT). Subjects and Methods. We studied 26 eyes with RRD
      before and after surgery, assessing visual acuity, the height of retinal
      detachment at the fovea (HRD), and morphologic changes of the macular region. The
      interval between the onset and surgery was also determined. We examined the
      external limiting membrane (ELM) after surgery and the continuity of the inner
      segment-outer segment junction (IS/OS junction) of the photoreceptor layer.
      Results. Impairment of visual acuity was observed when HRD was over 1,000  MU m,
      when there was outer nuclear layer edema before surgery, and when there was IS/OS
      junction disruption 3 months after surgery. However, 67% of eyes with a
      continuous ELM and IS/OS junction disruption 3 months after surgery eventually
      showed restoration of the continuity of IS/OS junction at 6 months. Conclusions.
      Impairment of visual acuity was observed in eyes with HRD >1,000  MU m,
      preoperative outer nuclear layer edema, and IS/OS junction disruption 3 months
      postoperatively. It is suggested that continuity of ELM might affect restoration
      of IS/OS junction after surgery for retinal detachment. 

PMID- 24563789
TI  - Pathophysiology of diabetic retinopathy.
AB  - Diabetes is now regarded as an epidemic, with the population of patients expected
      to rise to 380 million by 2025. Tragically, this will lead to approximately 4
      million people around the world losing their sight from diabetic retinopathy, the
      leading cause of blindness in patients aged 20 to 74 years. The risk of
      development and progression of diabetic retinopathy is closely associated with
      the type and duration of diabetes, blood glucose, blood pressure, and possibly
      lipids. Although landmark cross-sectional studies have confirmed the strong
      relationship between chronic hyperglycaemia and the development and progression
      of diabetic retinopathy, the underlying mechanism of how hyperglycaemia causes
      retinal microvascular damage remains unclear. Continued research worldwide has
      focussed on understanding the pathogenic mechanisms with the ultimate goal to
      prevent DR. The aim of this paper is to introduce the multiple interconnecting
      biochemical pathways that have been proposed and tested as key contributors in
      the development of DR, namely, increased polyol pathway, activation of protein
      kinase C (PKC), increased expression of growth factors such as vascular
      endothelial growth factor (VEGF) and insulin-like growth factor-1 (IGF-1),
      haemodynamic changes, accelerated formation of advanced glycation endproducts
      (AGEs), oxidative stress, activation of the renin-angiotensin-aldosterone system
      (RAAS), and subclinical inflammation and capillary occlusion. New pharmacological
      therapies based on some of these underlying pathogenic mechanisms are also
      discussed. 

PMID- 24563794
TI  - Evaluation of contrast sensitivity after single intravitreal triamcinolone
      injection for macular edema secondary to branch retinal vein occlusion.
AB  - Purpose. To evaluate visual acuity (VA), contrast sensitivity (CS), and central
      retinal thickness (CRT) after intravitreal triamcinolone acetonide (IVT)
      injection for macular edema secondary to branch retinal vein occlusion (BRVO).
      Methods. In this prospective study, a total of 21 eyes of 21 patients were
      included. VA, CS, and CRT were assessed at baseline and at 1, 3, and 6 months
      after a single IVT injection. Results. Mean age was 64.57 +/- 8.34 years. The
      mean baseline VA (LogMAR) increased from 1.11 +/- 0.63 to 0.55 +/- 0.39 (P <
      0.001), 0.60 +/- 0.40 (P < 0.001), and 0.78 +/- 0.39 (P = 0.07) at 1, 3, and 6
      months, respectively. The mean baseline CS (log CS) at 1 meter improved from 0.66
      +/- 0.49 to 1.11 +/- 0.32 (P < 0.001), 0.99 +/- 0.38 (P < 0.001), and 0.72 +/-
      0.37 (P = 0.8) at 1, 3, and 6 months, respectively. The mean baseline CS (log CS)
      at 3 meters improved from 0.34 +/- 0.41 to 0.74 +/- 0.41 (P < 0.001), 0.64 +/-
      0.44 (P = 0.036), and 0.46 +/- 0.49 (P = 0.8) at 1, 3, and 6 months,
      respectively. The mean baseline CRT decreased from 511 +/- 146 MUm to 242 +/- 119
      MUm, 277 +/- 131 MUm, and 402 +/- 166 MUm at 1, 3, and 6 months after IVT (P <
      0.001 for each). Conclusion. Single IVT injection improved VA and CS and reduced
      CRT at 1 and 3 months of treatment. VA and CS returned to baseline levels at 6
      months. 

PMID- 24563796
TI  - X-ray of one-sided "white lung" after central venous catheterization.
AB  - Complications during insertion of a subclavian central venous line are rare but
      potentially serious. This case report describes the radiological abnormality of a
      one-sided pleural effusion during a routine control directly after a difficult
      central venous catheterization. We illustrate the findings, the initial emergency
      management, and our procedure to rule out an iatrogenic hemothorax. Possible
      differential diagnoses and strategies for management of a suspected complication
      are discussed. 

PMID- 24563795
TI  - Noninvasive electromagnetic detection of bladder cancer.
AB  - Objectives. Normal and neoplastic human tissues have different electromagnetic
      properties. This study aimed to determine the diagnostic accuracy of noninvasive
      electromagnetic detection of bladder cancer (BC) by the tissue-resonance
      interaction method (TRIM-prob). Patients and Methods. Consecutive patients were
      referred for cystoscopy because of (i) microscopic or gross hematuria and/or
      irritative voiding symptoms and (ii) bladder ultrasounds and urinary cytology
      findings negative or just suspicious of malignancy. Patients were first submitted
      to TRIM-prob bladder scanning by a single investigator and then to cystoscopy by
      another investigator blind to TRIM-prob data. Results. In 125 evaluated patients
      cystoscopy was positive for BC in 47 and negative in the remaining 78;
      conversely, TRIM-prob bladder scanning was positive for BC in 53 and negative in
      72. In particular, TRIM-prob scanning yielded 7 false positives and only one
      false negative; therefore, its overall sensitivity, specificity, positive
      predictive value, negative predictive value, and diagnostic accuracy were 97.9%,
      89.9%, 86.8%, 98.6%, and 93.6%, respectively. Conclusions. TRIM-prob bladder
      scanning was a simple and quite accurate method for non-invasive electromagnetic
      detection of BC. If the elevated positive and negative predictive values will be
      replicated in further well-designed studies, it could be used to screen
      asymptomatic patients at high risk of BC. 

PMID- 24563797
TI  - Rhabdomyolysis and Cardiomyopathy in a 20-Year-Old Patient with CPT II
      Deficiency.
AB  - Aim. To raise the awareness of adult-onset carnitite palmitoyltransferase II
      deficiency (CPT II) by describing clinical, biochemical, and genetic features of
      the disease occurring in early adulthood. Method. Review of the case
      characteristics and literature review. Results. We report on a 20-year-old man
      presenting with dyspnea, fatigue, fever, and myoglobinuria. This was the second
      episode with such symptoms (the previous one being three years earlier). The
      symptoms occurred after intense physical work, followed by a viral infection
      resulting in fever treated with NSAIDs. Massive rhabdomyolysis was diagnosed,
      resulting in acute renal failure necessitating plasmapheresis and hemodialysis,
      acute hepatic lesion, and respiratory insufficiency. Additionally, our patient
      had cardiomyopathy with volume overload. After a detailed workup, CPT II
      deficiency was suspected. We did a sequencing analysis for exons 1, 3, and 4 of
      the CPT II gene and found that the patient was homozygote for Ser 113 Leu
      mutation in exon 3 of the CPT II gene. The patient recovery was complete except
      for the cardiomiopathy with mildly impaired systolic function. Conclusion.
      Whenever a patient suffers recurrent episodes of myalgia, followed by
      myoglobinuria due to rhabdomyolysis, we should always consider the possibility of
      this rare condition. The definitive diagnose of this condition is achieved by
      genetic testing. 

PMID- 24563798
TI  - Absence of substantial copy number differences in a pair of monozygotic twins
      discordant for features of autism spectrum disorder.
AB  - Autism spectrum disorder (ASD) is a highly heritable disease (~0.9) with a
      complex genetic etiology. It is initially characterized by altered cognitive
      ability which commonly includes impaired language and communication skills as
      well as fundamental deficits in social interaction. Despite the large amount of
      studies described so far, the high clinical diversity affecting the autism
      phenotype remains poorly explained. Recent studies suggest that rare genomic
      variations, in particular copy number variation (CNV), may account for a
      significant proportion of the genetic basis of ASD. The use of disease-discordant
      monozygotic twins represents a powerful strategy to identify de novo and
      inherited CNV in the disorder. Here we present the results of a comparative
      genome hybridization (CGH) analysis with a pair of monozygotic twins affected of
      ASD with significant differences in their clinical manifestations that specially
      affect speech language impairment and communication skills. Array CGH was
      performed in three different tissues: blood, saliva, and hair follicle, in an
      attempt to identify germinal and somatic CNV regions that may explain these
      differences. Our results argue against a role of large CNV rearrangements as a
      molecular etiology of the observed differences. This forwards future research to
      explore de novo point mutation and epigenomic alterations as potential
      explanations of the observed clinical differences. 

PMID- 24563799
TI  - Diabetic muscle infarction: a rare cause of acute limb pain in dialysis patients.
AB  - Diabetic muscle infarction is a rare microangiopathic complication occurring in
      patients with advanced diabetes mellitus. Diabetic patients with chronic kidney
      disease stage Vd are prone to develop this complication. The presenting symptom
      is a localized painful swelling of the affected limb. Symptoms usually resolve
      spontaneously during the following weeks, but frequent relapse can occur and in
      some cases swelling may lead to compartment syndrome. Biochemical blood analyses
      show an elevated C-reactive protein, but creatine kinase is often normal.
      Diagnosis can be made on clinical presentation and imaging, with magnetic
      resonance imaging as the gold standard. Histology is often not contributive.
      Treatment consists of rest, analgesics, rigorous glycemic control and low-dose
      aspirin. Severe cases of compartment syndrome require fasciotomy. In the current
      paper, we present two diabetic patients with cystic fibrosis, who are treated
      with automated peritoneal dialysis and suffered from episodic lower limb
      infarction. We subsequently review 48 episodes of diabetic muscle infarction
      previously reported in the literature in patients with end-stage renal disease. 

PMID- 24563800
TI  - A Retrospectively Diagnosed Case of IgG4-Related Tubulointerstitial Nephritis
      Showing Good Renal Outcome and Pathological Progress.
AB  - A 74-year-old man was hospitalized for diabetic nephropathy evaluation and
      assessment of the effect of treatment on his tubulointerstitial nephritis (TIN).
      When he was 62 years old, he developed polyarthralgia and had superficial lymph
      node swelling, mildly increased serum creatinine concentration,
      hypergammaglobulinemia, hypocomplementemia, high serum IL-2R level, and positive
      titer of antinuclear antibody. Several tissues were biopsied. Mild chronic
      sialadenitis and reactive lymphadenitis were identified. Renal specimen showed
      mild glomerular ischemia, extensive storiform fibrosis, and abundant infiltrating
      monocytes and plasma cells. He was treated with oral prednisolone and
      cyclophosphamide. After the treatment, most of his clinical parameters quickly
      returned to within the reference range. However, he developed diabetes mellitus
      soon after steroid therapy. At the time of rebiopsy, a high level of serum IgG4
      was detected. The second renal biopsy showed diabetic nephropathy without any
      tubulointerstitial damage. The first biopsied tissues were retrospectively
      investigated. Large numbers of IgG4-positive plasma cells were detected in the
      kidneys and lymph nodes. A retrospective diagnosis of IgG4-related TIN with lymph
      node involvement was made. In conclusion, this paper describes a retrospectively
      diagnosed case of IgG4-related TIN with lymph node involvement, showing good
      clinical and pathological prognosis. 

PMID- 24563801
TI  - Severe Symptomatic Hypermagnesemia Associated with Over-the-Counter Laxatives in
      a Patient with Renal Failure and Sigmoid Volvulus.
AB  - Hypermagnesemia is an uncommon but a potentially serious clinical condition. Over
      the-counter magnesium containing products are widely used as antacids or
      laxatives. Although generally well tolerated in patients with normal renal
      function, their unsupervised use in the elderly can result in severe symptomatic
      hypermagnesemia, especially in those patients with concomitant renal failure and
      bowel disorders. We report a case of severe symptomatic hypermagnesemia
      associated with over-the-counter laxatives in a 70-year-old male patient with
      renal failure and sigmoid volvulus, who was successfully treated with
      hemodialysis. 

PMID- 24563802
TI  - The Morbidity of Reoperative Surgery for Recurrent Benign Nodular Goitre: Impact
      of Previous Unilateral Thyroid Lobectomy versus Subtotal Thyroidectomy.
AB  - Background. Subtotal thyroidectomy (STT) was previously considered the gold
      standard in the surgical management of multinodular goitre despite its propensity
      for recurrence. Our aim was to assess whether prior STT or unilateral lobectomy
      was associated with increased reoperative morbidity. Methods. A retrospective
      analysis was conducted extracting data from our endocrine surgical database for
      the period from January 1991 to June 2006. Two patient groups were defined: Group
      1 consisted of patients with previous unilateral thyroid lobectomy; Group 2 had
      undergone previous STT. Specific outcomes investigated were transient and
      permanent recurrent laryngeal nerve (RLN) injury and hypoparathyroidism. Results.
      494 reoperative cases were performed which consisted of 259 patients with
      previous unilateral lobectomy (Group 1) and 235 patients with previous subtotal
      thyroidectomy (Group 2). A statistically significant increase relating to
      previous STT was demonstrated in both permanent RLN injury (0.77% versus 3.4%, RR
      4.38, P = 0.038) and permanent hypoparathyroidism (1.5% versus 5.1%, RR 3.14, P =
      0.041). Transient nerve injury and hypocalcaemia incidence was comparable.
      Conclusions. Reoperative surgery following subtotal thyroidectomy is associated
      with a significantly increased risk of permanent recurrent laryngeal nerve injury
      and hypoparathyroidism when compared with previous unilateral thyroidectomy.
      Subtotal thyroidectomy should therefore no longer be recommended in the
      management of multinodular goitre. 

PMID- 24563804
TI  - Synchronized Analysis of FTIR Spectra and GCMS Chromatograms for Evaluation of
      the Thermally Degraded Vegetable Oils.
AB  - Fourier Transform Infrared (FTIR) and Gas Chromatography Mass Spectrometry (GCMS)
      are two common instruments used for analysis of edible oils. The output signal is
      often analysed on the software attached to the workstations. The processing
      software is usually individualised for a specific source. The output of GCMS
      cannot be analysed on the FTIR hence analysts often need to juggle between
      instruments when multiple techniques are employed. This could become exhaustive
      when a large dataset is involved. This paper reports a synchronised approach for
      analysis of signal from FTIR and GCMS. The algorithm is demonstrated on a dataset
      of edible oils to investigate the thermal degradation of seven types of edible
      oils treated at 100 degrees C and 150 degrees C. The synchronised routines
      identify peaks present in FTIR and GCMS spectra/chromatograms where the
      information is subsequently extracted onto peak tables for further analysis. In
      this study, it is found that palm based products and corn oils were relatively
      more stable with higher content of antioxidants tocopherols and squalene. As a
      conclusion, this approach allows simultaneous analysis of signal from multiple
      sources and samples enhancing the efficiency of the signal processing process. 

PMID- 24563803
TI  - Crotalus durissus collilineatus Venom Induces TNF- alpha and IL-10 Production in
      Human Peripheral Blood Mononuclear Cells.
AB  - Snake venom has been the subject of numerous studies in an attempt to find
      properties and biological effects that may be beneficial to man. In this study we
      evaluated in vitro the effects of Crotalus durissus terrificus (Cdt) and Crotalus
      durissus collilineatus (Cdc) venom in human peripheral blood mononuclear cells
      (PBMCs). At 24 h, a significant decrease of viable cells was observed in cells
      stimulated with the Cdc venom at 0.0005 mg/mL and 0.005 mg/mL compared to the
      negative control. At 48 h, a significant decrease of viable cells was observed
      only in cells stimulated with Cdc venom at 0.005 mg/mL. A significant increase of
      TNF- alpha and IL-10 was detected 48 hours after culture of PBMC with Cdc, but
      not with Cdt venom. The expression of CD69 and PD1 (programmed death-1),
      activation and regulatory cell markers, on CD8+ and CD8- T cells did not change
      in the presence of Cdt and Cdc venom. Our results suggest the presence of
      proinflammatory and anti-inflammatory components in the Cdc venom. Further
      analysis should be done to identify those Cdc venom components as it has been
      done for the Cdt venom by other authors, indicating that modulatory components
      are found in the venom of different species of Crotalus snakes. 

PMID- 24563805
TI  - Leaving tissue associated with infrequent intracranial EEG seizure onsets is
      compatible with post-operative seizure freedom.
AB  - Identify seizure onset electrodes that need to be resected for seizure freedom in
      children undergoing intracranial electroencephalography recording for treatment
      of medically refractory epilepsy. All children undergoing intracranial
      electroencephalography subdural grid electrode placement at the Children's
      Hospital of Philadelphia from 2002-2008 were asked to enroll. We utilized
      intraoperative pictures to determine the location of the electrodes and define
      the resection cavity. A total of 15 patients had surgical fields that allowed for
      complete identification of the electrodes over the area of resection. Eight of 15
      patients were seizure free after a follow up of 1.7 to 8 yr. Only one seizure
      free patient had complete resection of all seizure onset associated tissue.
      Seizure free patients had resection of 64.1% of the seizure onset electrode
      associated tissue, compared to 35.2% in the not seizure free patients (p=0.05).
      Resection of tissue associated with infrequent seizure onsets did not appear to
      be important for seizure freedom. Resecting >= 90% of the electrodes from the
      predominant seizure contacts predicted post-operative seizure freedom (p=0.007).
      The best predictor of seizure freedom was resecting >= 90% of tissue involved in
      majority of a patient's seizures. Resection of tissue under infrequent seizure
      onset electrodes was not necessary for seizure freedom.

PMID- 24563806
TI  - Research Participants' Understanding of and Reactions to Certificates of
      Confidentiality.
AB  - BACKGROUND: Certificates of Confidentiality are intended to facilitate
      participation in critical public health research by protecting against forced
      disclosure of identifying data in legal proceedings, but little is known about
      the effect of Certificate descriptions in consent forms. METHODS: To gain
      preliminary insights, we conducted qualitative interviews with 50 HIV-positive
      individuals in Durham, North Carolina to explore their subjective understanding
      of Certificate descriptions and whether their reactions differed based on
      receiving a standard versus simplified description. RESULTS: Most interviewees
      were neither reassured nor alarmed by Certificate information, and most said it
      would not influence their willingness to participate or provide truthful
      information. However, compared with those receiving the simplified description,
      more who read the standard description said it raised new concerns, that their
      likelihood of participating would be lower, and that they might be less
      forthcoming. Most interviewees said they found the Certificate description clear,
      but standard-group participants often found particular words and phrases
      confusing, while simplified-group participants more often questioned the
      information's substance. CONCLUSIONS: Valid informed consent requires
      comprehension and voluntariness. Our findings highlight the importance of
      developing consent descriptions of Certificates and other confidentiality
      protections that are simple and accurate. These qualitative results provide rich
      detail to inform a larger, quantitative study that would permit further rigorous
      comparisons.

PMID- 24563808
TI  - Patterns of Violence Exposure and Sexual Risk in Low-Income, Urban African
      American Girls.
AB  - OBJECTIVE: This study examined the relationship between violence exposure and
      sexual risk-taking among low-income, urban African American (AA) adolescent
      girls, considering overlap among different types and characteristics of violence.
      METHODS: AA adolescent girls were originally recruited from outpatient mental
      health clinics serving urban, mostly low-SES communities in Chicago, IL as part
      of a two-year longitudinal investigation of HIV-risk behavior. A subsequent
      follow-up was completed to assess lifetime history of trauma and violence
      exposure. The current study (N=177) included violence exposure and sexual risk
      behavior reported at the most recent interview (ages 14-22). Multiple regression
      was used to examine combined and unique contributions of different types, ages,
      settings, and perpetrators or victims of violence to variance in sexual risk.
      RESULTS: More extensive violence exposure and cumulative exposure to different
      kinds of violence were associated with overall unsafe sex, more partners, and
      inconsistent condom use. The most significant unique predictors, accounting for
      overlap among different forms of violence, were physical victimization,
      adolescent exposure, neighborhood violence, and violence involving dating
      partners. CONCLUSIONS: These findings put sexual risk in the context of broad
      traumatic experiences but also suggest that the type and characteristics of
      violence exposure matter in terms of sexual health outcomes. Violence exposure
      should be addressed in efforts to reduce STIs among low-income, urban African
      American girls.

PMID- 24563809
TI  - One-Pot Asymmetric Nitro-Mannich/Hydroamination Cascades for the Synthesis of
      Pyrrolidine Derivatives: Combining Organocatalysis and Gold Catalysis.
AB  - The highly enantioselective preparation of trisubstituted pyrrolidine derivatives
      employing a one-pot nitro-Mannich/hydroamination cascade is reported. This
      cascade approach utilizes an asymmetric bifunctional organocatalytic nitro
      Mannich reaction followed by a gold-catalyzed allene hydroamination reaction. The
      products are afforded in good yields and excellent diastereo- and
      enantioselectivities.

PMID- 24563807
TI  - Cks1: Structure, Emerging Roles and Implications in Multiple Cancers.
AB  - Deregulation of the cell cycle results in loss of normal control mechanisms that
      prevent aberrant cell proliferation and cancer progression. Regulation of the
      cell cycle is a highly complex process with many layers of control. One of these
      mechanisms involves timely degradation of CDK inhibitors (CKIs) like p27Kip1 by
      the ubiquitin proteasomal system (UPS). Cks1 is a 9 kDa protein which is
      frequently overexpressed in different tumor subtypes, and has pleiotropic roles
      in cell cycle progression, many of which remain to be fully characterized. One
      well characterized molecular role of Cks1 is that of an essential adaptor that
      regulates p27Kip1 abundance by facilitating its interaction with the SCF-Skp2 E3
      ligase which appends ubiquitin to p27Kip1 and targets it for degradation through
      the UPS. In addition, emerging research has uncovered p27Kip1-independent roles
      of Cks1 which have provided crucial insights into how it may be involved in
      cancer progression. We review here the structural features of Cks1 and their
      functional implications, and also some recently identified Cks1 roles and their
      involvement in breast and other cancers.

PMID- 24563810
TI  - The Impact of Hypotensive Epidural Anesthesia on Distal and Proximal Tissue
      Perfusion in Patients Undergoing Total Hip Arthroplasty.
AB  - : Little data exists to detail the effect of hypotensive epidural anesthesia on
      differential tissue oxygenation changes above and below the level of neuraxial
      blockade. This study was designed to investigate tissue oxygenation in a clinical
      setting, using non-invasive near-infrared spectroscopy. METHODS: Patients aged 18
      to 85 years scheduled to undergo primary total hip arthroplasty were enrolled.
      Muscle oxygenation saturation was measured above and below the level of neuraxial
      blockade (deltoid and vastus lateralis muscles). Other continuously recorded
      parameters included cardiac output, stroke volume, heart rate, invasive mean
      arterial blood pressure and arterial oxygen saturation. Recordings of muscle
      oxygenation were compared over time separately for upper and lower extremity.
      RESULTS: 10 patients were enrolled. We found an intermittent and significant
      unadjusted decline of mean muscle oxygenation saturation in the vastus lateralis
      muscle during first part of the surgery (nadir 2nd quintile: 71.0% vs. 63.3%,
      p<0.0001). This decline was followed by a return to baseline towards the end of
      the surgery (71.0% vs. 69.1%, p=0.3429). Mean muscle oxygenation saturation did
      not change for the same period of time in the deltoid muscle. When adjusting for
      covariates, the changes in muscle tissue oxygenation remained significant.
      CONCLUSION: These results indicate that muscle oxygenation saturation, a
      surrogate parameter for tissue perfusion, is decreased by hypotensive epidural
      anesthesia, but only within the functional limits of the neuraxial blockade. The
      etiology of these findings remains to be elucidated.

PMID- 24563811
TI  - Flavin-Dependent Thymidylate Synthase as a Drug Target for Deadly Microbes:
      Mutational Study and a Strategy for Inhibitor Design.
AB  - The identification of flavin-dependent thymidylate synthase (FDTS) as an
      essential enzyme and its occurrence in several pathogenic microbes opens
      opportunities for using FDTS enzyme as an excellent target for new antimicrobial
      drug discovery. In contrast to the human thymidylate synthase enzyme that
      utilizes methylene-tetrahydrofolate (CH2H4 folate) for the conversion of dUMP to
      dTMP, the microbial enzymes utilize an additional non-covalently bound FAD
      molecule for the hydride transfer from NAD(P)H. The structural and mechanistic
      differences between the human and microbial enzymes present an attractive
      opportunity for the design of antimicrobial compounds specific for the pathogens.
      We have determined the crystal structure of FDTS enzyme in complex with the
      methyl donor, CH2H4 folate. We describe here the structure of a FDTS mutant and
      compare it with other FDTS complex structures, including a FDTS-CH2H4 folate
      complex. We identified a conformational change essential for substrate binding
      and propose a strategy for the design of FDTS specific inhibitors.

PMID- 24563812
TI  - Microtubule defects & Neurodegeneration.
AB  - One of the major challenges facing the long term survival of neurons is their
      requirement to maintain efficient axonal transport over long distances. In humans
      as large, long-lived vertebrates, the machinery maintaining neuronal transport
      must remain efficient despite the slow accumulation of cell damage during aging.
      Mutations in genes encoding proteins which function in the transport system
      feature prominently in neurologic disorders. Genes known to cause such disorders
      and showing traditional Mendelian inheritance have been more readily identified.
      It has been more difficult, however, to isolate factors underlying the complex
      genetics contributing to the more common idiopathic forms of neurodegenerative
      disease. At the heart of neuronal transport is the rail network or scaffolding
      provided by neuron specific microtubules (MTs). The importance of MT dynamics and
      stability is underscored by the critical role tau protein plays in MT-associated
      stabilization versus the dysfunction seen in Alzheimer's disease, frontotemporal
      dementia and other tauopathies. Another example of the requirement for tight
      regulation of MT dynamics is the need to maintain balanced levels of post
      translational modification of key MT building-blocks such as alpha-tubulin.
      Tubulins require extensive polyglutamylation at their carboxyl-terminus as part
      of a novel post-translational modification mechanism to signal MT growth versus
      destabilization. Dramatically, knock-out of a gene encoding a deglutamylation
      family member causes an extremely rapid cell death of Purkinje cells in the
      ataxic mouse model, pcd. This review will examine a range of neurodegenerative
      conditions where current molecular understanding points to defects in the
      stability of MTs and axonal transport to emphasize the central role of MTs in
      neuron survival.

PMID- 24563813
TI  - Improvement of antidepressant-induced sweating with as-required benztropine.

PMID- 24563814
TI  - A relationship between factitious disorder and borderline personality disorder.

PMID- 24563815
TI  - Buprenorphine/Naloxone treatment in the correctional setting: use or misuse.

PMID- 24563816
TI  - Psychogenic nonepileptic seizures.
AB  - OBJECTIVE: All patients who exhibit seizure-like behavior cannot be evaluated by
      video-electroencephalography if their routine EEGs are negative, as this would be
      impractical and cost-prohibitive. The present article reviews a decision-making
      process that can be used for determining if further neurological evaluation is
      needed, the differential diagnoses and potential comorbidities involved when
      making this determination, and an approach to conveying the psychogenic
      nonepileptic seizure diagnosis to the patient that may help reduce symptom
      frequency. DESIGN: Literature review. CONCLUSION: Psychogenic seizures are not
      caused by abnormal brain electrical activity. The symptoms of psychogenic
      seizures usually reflect a psychological conflict or a psychiatric disorder.
      However, psychogenic seizures are not "purposely" produced by the patient, and
      the patient is not aware that the seizures are non-epileptic, so the patient may
      become very anxious over having these symptoms. The presentation of the
      differential diagnosis should be done early in the course of treatment for better
      patient acceptance, and treatment options should be presented early in the
      evaluation period.

PMID- 24563817
TI  - Insomnia and attention deficit hyperactivity disorder in pediatrics: a checklist
      for parents.
AB  - Attention deficit hyperactivity disorder is a commonly diagnosed condition in the
      pediatric as well as adult psychiatric population. Attention deficit
      hyperactivity disorder has undoubtedly been over diagnosed and treated with both
      stimulants and non-stimulants over the past few decades. Behavior problems in
      children are commonly noticed both by parents and teachers, leading to the
      formulation of attention deficit hyperactivity disorder diagnosis. Insomnia, on
      the other hand, is not as readily detected by parents and may result in
      behavioral problems at school. Several medical conditions responsible for causing
      insomnia may need to be ruled out before the diagnosis of attention deficit
      hyperactivity disorder is confirmed. In this article, we highlight symptoms
      common both to insomnia and attention deficit hyperactivity disorder by
      development of a checklist to help delineate the two conditions. The purpose of
      this checklist is to provide informational and educational tools both for parents
      and teachers to distinguish insomnia from attention deficit hyperactivity
      disorder. The ultimate goal of this paper is to improve diagnostic screening for
      attention deficit hyperactivity disorder by excluding conditions such as insomnia
      that may masquerade as attention deficit hyperactivity disorder. 

PMID- 24563818
TI  - Preventing wounds from healing: clinical prevalence and relationship to
      borderline personality.
AB  - In medico-economic studies, wound care has been shown to be expensive but is
      seemingly unavoidable given an aging population and the high community rates of
      diabetes and obesity. Astonishingly, however, some impaired wound resolution is
      intentional or purposeful. According to our review of seven clinical samples, the
      prevalence of preventing wounds from healing varies from 0.8 percent in a cardiac
      stress-testing sample to 13.3 percent in a psychiatric inpatient sample. These
      variations in prevalence suggest that the more psychiatric loading in a given
      population, the higher the potential rate of preventing wounds from healing. In
      addition, statistical analyses indicate that preventing wounds from healing is
      consistently associated with borderline personality disorder. This link is most
      likely explained through the psychodynamics of self-harm behavior. Self-harm
      behavior is an inherent feature of borderline personality disorder, and
      preventing wounds from healing may be a self-injury equivalent among some
      patients with this particular personality dysfunction. Among participants with
      this Axis II disorder, women tend to report higher rates of preventing wounds
      from healing than men. Overall findings suggest that clinicians need to be alert
      to unexpected delays with wound healing, particularly in patients with
      psychiatric histories, and consider that such behavior is likely to be associated
      with borderline personality disorder. 

PMID- 24563819
TI  - Prescription monitoring programs: to use or not to use.

PMID- 24563820
TI  - The Global HIV Archive: Facilitating the Transition from Science to Practice of
      Efficacious HIV Prevention Interventions.
AB  - This paper describes the development, content, and capabilities of the online
      Global HIV Archive (GHA). With the goal of facilitating widespread adaptation and
      appropriate use of efficacious HIV prevention programs throughout the globe, GHA
      has: first, expanded and updated the search for HIV prevention programs
      originating in low-resource countries; second, identified those meritorious HIV
      prevention programs meeting established efficacy criteria of technical merit,
      replicability, and positive outcomes; third, prepared both implementation and
      evaluation materials from the efficacious programs for public use; fourth,
      developed interactive wizards or capacity-building tools to facilitate
      appropriate program selection, implementation, and adaptation; and, fifth, made
      the efficacious programs and accompanying wizards available to health
      practitioners throughout the globe in both printed and online formats.

PMID- 24563821
TI  - Selective Neuronal and Brain Regional Expession of IL-2 in IL2P 8-GFP Transgenic
      Mice: Relation to Sensorimotor Gating.
AB  - Brain-derived interleukin-2 (IL-2) has been implicated in diseases processes that
      arise during CNS development (e.g., autism) to neurodegenerative alterations
      involving neuroinflammation (e.g., Alzheimer's disease). Progress has been
      limited, however, because the vast majority of current knowledge of IL-2's
      actions on brain function and behavior is based on the use exogenously
      administered IL-2 to make inferences about the function of the endogenous
      cytokine. Thus, to identify the cell-type(s) and regional circuitry that express
      brain-derived IL-2, we used B6.Cg-Tg/ IL2-EGFP17Evr (IL2p8-GFP) transgenic mice,
      which express green fluorescent protein (GFP) in peripheral immune cells known to
      produce IL-2. We found that the IL2-GFP transgene was localized almost
      exclusively to NeuN-positive cells, indicating that the IL-2 is produced
      primarily by neurons. The IL2-GFP transgene was expressed in discrete nuclei
      throughout the rostral-caudal extent of the brain and brainstem, with the highest
      levels found in the cingulate, dorsal endopiriform nucleus, lateral septum,
      nucleus of the solitary tract, magnocellular/gigantocellular reticular formation,
      red nucleus, entorhinal cortex, mammilary bodies, cerebellar fastigial nucleus,
      and posterior interposed nucleus. Having identified IL-2 gene expression in brain
      regions associated with the regulation of sensorimotor gating (e.g., lateral
      septum, dorsal endopiriform nucleus, entorhinal cortex, striatum), we compared
      prepulse inhibition (PPI) of the acoustic startle response in congenic mice bred
      in our lab that have selective loss of the IL-2 gene in the brain versus the
      peripheral immune system, to test the hypothesis that brain-derived IL-2 plays a
      role in modulating PPI. We found that congenic mice devoid of IL-2 gene
      expression in both the brain and the peripheral immune system, exhibited a modest
      alteration of PPI. These finding suggest that IL2p8-GFP transgenic mice may be a
      useful tool to elucidate further the role of brain-derived IL-2 in normal CNS
      function and disease.

PMID- 24563823
TI  - High-affinity peptide-based anticancer vaccination to overcome resistance to
      immunostimulatory antibodies.
AB  - We tested how to eradicate long-established immunogenic tumors that were
      resistant to the monoclonal antibody-mediated blockade of PD-L1 (PD-1 ligand 1)
      and cytotoxic T lymphocyte-associated protein 4 (CTLA4). Bacterial vaccination
      with a tumor-specific peptide exhibiting a high affinity for its respective MHC
      molecule consistently eradicated tumors when combined with a PD-L1 blocking
      antibody. This approach can be translated to the clinic by combining cancer cell
      whole-exome sequencing with algorithms to identify mutant peptides with high
      peptide-MHC binding affinity.

PMID- 24563822
TI  - The Influence of Energetic Factors on Biomarkers of Postmenopausal Breast Cancer
      Risk.
AB  - Strong and consistent evidence exists that physical activity reduces breast
      cancer risk by 10-25 %, and several proposed biologic mechanisms have now been
      investigated in randomized, controlled, exercise intervention trials. Leading
      hypothesized mechanisms relating to postmenopausal breast cancer include
      adiposity, endogenous sex hormones, insulin resistance, and chronic low-grade
      inflammation. In addition, other pathways are emerging as potentially important,
      including those involving oxidative stress and telomere length, global DNA
      hypomethylation, immune function, and vitamin D exposure. Recent exercise trials
      in overweight/obese postmenopausal women implicate weight loss as a mechanism
      whereby exercise induces favorable changes in circulating estradiol levels and
      other biomarkers as well. Still it is plausible that some exercise-induced
      biomarker changes do not require loss of body fat, whereas others depend on
      abdominal fat loss. We highlight the latest findings from randomized, controlled
      trials of healthy postmenopausal women, relating exercise to proposed biomarkers
      for postmenopausal breast cancer risk.

PMID- 24563824
TI  - MicroRNAs and Cardiovascular Disease.
AB  - MicroRNAs (miRNAs) regulate gene expression by binding to their targets and
      promoting RNA degradation and/or inhibiting protein translation. In recent years,
      miRNAs have revolutionized our understanding of gene regulatory networks,
      providing new prospective tools to manage disease. Atherosclerosis and other
      cardiovascular diseases are a leading cause of disability and death in the US and
      in other western populations and pose an enormous burden on our healthcare
      system. Altered lipid homeostasis in liver or in the artery wall, and disruption
      of endothelial and smooth muscle cell function have been shown to contribute to
      the onset and progression of cardiovascular disease. This review focuses on
      recent advances in the field of vascular biology- and lipid metabolism-related
      miRNomics.

PMID- 24563827
TI  - Connecting parents of children with chronic pain through art therapy.
AB  - OBJECTIVES: To help address the unique needs of parents of children with chronic
      pain, a four module, parent-only, group art therapy curriculum was designed and
      implemented within an interdisciplinary pain rehabilitation treatment program. We
      evaluated perceived satisfaction and helpfulness of the group intervention.
      METHODS: Fifty-three parents of children experiencing chronic pain enrolled in a
      day hospital interdisciplinary pain rehabilitation program participated. The
      voluntary parent art therapy group was offered one time per week for one hour.
      Participants completed a measure of satisfaction, helpfulness, and perceived
      social support at the end of each group session. RESULTS: Parents enjoyed
      participating in the group, agreed that they would try art therapy again, and
      found it to be a helpful, supportive, and validating experience. CONCLUSIONS:
      Initial results are promising that group art therapy is an appropriate and
      helpful means of supporting parents of children with chronic pain during
      interdisciplinary pain rehabilitation.

PMID- 24563826
TI  - Yeast telomere maintenance is globally controlled by programmed ribosomal
      frameshifting and the nonsense-mediated mRNA decay pathway.
AB  - We have previously shown that ~10% of all eukaryotic mRNAs contain potential
      programmed -1 ribosomal frameshifting (-1 PRF) signals and that some function as
      mRNA destabilizing elements through the Nonsense-Mediated mRNA Decay (NMD)
      pathway by directing translating ribosomes to premature termination codons. Here,
      the connection between -1 PRF, NMD and telomere end maintenance are explored.
      Functional -1 PRF signals were identified in the mRNAs encoding two components of
      yeast telomerase, EST1 and EST2, and in mRNAs encoding proteins involved in
      recruiting telomerase to chromosome ends, STN1 and CDC13. All of these elements
      responded to mutants and drugs previously known to stimulate or inhibit -1 PRF,
      further supporting the hypothesis that they promote -1 PRF through the canonical
      mechanism. All affected the steady-state abundance of a reporter mRNA and the
      wide range of -1 PRF efficiencies promoted by these elements enabled the
      determination of an inverse logarithmic relationship between -1 PRF efficiency
      and mRNA accumulation. Steady-state abundances of the endogenous EST1, EST2, STN1
      and CDC13 mRNAs were similarly inversely proportional to changes in -1 PRF
      efficiency promoted by mutants and drugs, supporting the hypothesis that
      expression of these genes is post-transcriptionally controlled by -1 PRF under
      native conditions. Overexpression of EST2 by ablation of -1 PRF signals or
      inhibition of NMD promoted formation of shorter telomeres and accumulation of
      large budded cells at the G2/M boundary. A model  is presented describing how
      limitation and maintenance of correct stoichiometries of telomerase components by
      -1 PRF is used to maintain yeast telomere length. 

PMID- 24563825
TI  - Condensins and 3D Organization of the Interphase Nucleus.
AB  - Condensins are conserved multi-subunit protein complexes that participate in
      eukaryotic genome organization. Well known for their role in mitotic chromosome
      condensation, condensins have recently emerged as integral components of diverse
      interphase processes. Recent evidence shows that condensins are involved in
      chromatin organization, gene expression, and DNA repair and indicates
      similarities between the interphase and mitotic functions of condensin. Recent
      work has enhanced our knowledge of how chromatin architecture is dynamically
      regulated by condensin to impact essential cellular processes.

PMID- 24563828
TI  - Loss of arbuscular mycorrhizal fungal diversity in trap cultures during long-term
      subculturing.
AB  - Long-term successional dynamics of an inoculum of arbuscular mycorrhizal fungi
      (AMF) associated with the maize rhizosphere (from traditionally managed
      agroecosystems in Los Tuxtlas, Veracruz, Mexico), was followed in Bracchiaria
      comata trap cultures for almost eight years. The results indicate that AMF
      diversity is lost following long-term subculturing of a single plant host
      species. Only the dominant species, Claroideoglomus etunicatum, persisted in pot
      cultures after 13 cycles. The absence of other morphotypes was demonstrated by an
      18S rDNA survey, which confirmed that the sequences present solely belonged to C.
      etunicatum. Members of Diversisporales were the first to decrease in diversity,
      and the most persistent species belonged to Glomerales. 

PMID- 24563829
TI  - Incipient loss of flagella in the genus Geolegnia: the emergence of a new clade
      within Leptolegnia?
AB  - The genus Geolegnia represents a poorly documented group of saprolegnialean
      oomycetes isolated from soils as free-living organisms. Although it is
      morphologically similar to the facultative parasitic genus Leptolegnia, Geolegnia
      presents the uncommon property of having lost a flagellate stage in its
      lifecycle. Based on ITS and large subunit (LSU) rRNA sequence data, we show
      Geolegnia to be basal to Leptolegnia, and also introduce Geolegnia helicoides sp.
      nov. Using sequence data of Leptolegnia available in GenBank, supplemented by
      data derived from culture collections, we show that Geolegnia is nested within
      Leptolegnia, a genus characterised by its "conventional" biflagellate life cycle.
      The emergence of Geolegnia is therefore seen as a recent event, and we suggest
      here an evolutionary context where this loss might have been advantageous. Based
      on this study, Leptolegnia remains paraphyletic, awaiting the redefinition of
      genera in this complex. 

PMID- 24563830
TI  - A new species of Gymnoascus with verruculose ascospores.
AB  - A new species, Gymnoascus verrucosus sp. nov., isolated from soil from Kalyan
      railway station, Maharashtra, India, is described and illustrated. The
      distinctive morphological features of this taxon are its verruculose ascospores
      (ornamentation visible only under SEM) and its deer antler-shaped short peridial
      appendages. The small peridial appendages originate from open mesh-like
      gymnothecial ascomata made up of thick-walled, smooth peridial hyphae. The
      characteristic morphology of the fungus is not formed in culture where it has
      very restricted growth and forms arthroconidia. Phylogenetic analysis of
      different rDNA gene sequences (ITS, LSU, and SSU) demonstrates its placement in
      Gymnoascaceae and reveal its phylogenetic relatedness to other species of
      Gymnoascus, especially G. petalosporus and G. boliviensis. The generic concept of
      Gymnoascus is consequently now broadened to include species with verruculose
      ascospores. A key to the accepted 19 species is also provided. 

PMID- 24563831
TI  - Septoria-like pathogens causing leaf and fruit spot of pistachio.
AB  - Several species of Septoria are associated with leaf and fruit spot of pistachio
      (Pistacia vera), though their identity has always been confused, making
      identification problematic. The present study elucidates the taxonomy of the
      Septoria spp. associated with pistachio, and distinguishes four species
      associated with this host genus. Partial nucleotide sequence data for five gene
      loci, ITS, LSU, EF-1alpha, RPB2 and Btub were generated for a subset of isolates.
      Cylindroseptoria pistaciae, which is associated with leaf spots of Pistacia
      lentiscus in Spain, is characterised by pycnidial conidiomata that give rise to
      cylindrical, aseptate conidia. Two species of Septoria s. str. are also
      recognised on pistachio, S. pistaciarum, and S. pistaciae. The latter is part of
      the S. protearum species complex, and appears to be a wide host range pathogen
      occurring on hosts in several different plant families. Septoria pistacina, a
      major pathogen of pistachio in Turkey, is shown to belong to Pseudocercospora,
      and not Septoria as earlier suspected. Other than for its pycnidial conidiomata,
      it is a typical species of Pseudocercospora based on its smooth, pigmented
      conidiogenous cells and septate conidia. This phenomenon has also been observed
      in Pallidocercospora, and seriously questions the value of conidiomatal structure
      at generic level, which has traditionally been used to separate hyphomycetous
      from coelomycetous ascomycetes. Other than DNA barcodes to facilitate the
      molecular identification of these taxa occurring on pistachio, a key is also
      provided to distinguish species based on morphology. 

PMID- 24563832
TI  - Passalora stromatica sp. nov. associated with leaf spots of Tithonia diversifolia
      in Brazil.
AB  - Tithonia diversifolia, a member of Compositae native to Central America that
      produces showy sunflower-like flowers, became an invasive weed in other
      continents after it was introduced as an ornamental. Little is known about fungal
      pathogens infecting this plant. Knowledge of its mycobiota is of interest for
      future biocontrol programmes for T. diversifolia. In Brazil, a cercosporoid
      hyphomycete was found associated with intense leaf-spotting of this plant. Based
      on morphological and molecular data it was recognized as representing a new
      species of Passalora, and the name Passalora stromatica sp.nov. is introduced
      here for this taxon. This fungus is described and illustrated herein. It is
      possible that this fungus is playing a role in Brazil in reducing the
      invasiveness of T. diversifolia as, contrarily to what has been reported for
      countries in Africa and Asia, it remains mostly as a garden escape or rural plant
      in Brazil. 

PMID- 24563833
TI  - Rasamsonia pulvericola sp. nov., isolated from house dust.
AB  - In the course of a global survey of the indoor mycobiota, we sampled and analysed
      settled dust from 87 buildings from 14 countries, using both a modified dilution
      to-extinction method and 454-pyrosequencing. Rasamsonia is a recently established
      genus including thermotolerant or thermophilic species, five of which have been
      isolated from humans, including the emerging pathogen R. argillacea. A new
      species, R. pulvericola, was recovered from one residence in Songkhla, Thailand,
      and is morphologically characterised and compared phylogenetically with other
      members of the genus. Rasamsonia pulvericola forms a clade with R. brevistipitata
      and shares morphological characters such as usually biverticillate and never
      terverticillate conidiophores, and subglobose to ellipsoidal conidia. It has a
      lower maximum growth temperature and is the first mesophilic species added to the
      genus. The ITS sequence of R. pulvericola was not detected in the 454
      pyrosequencing data for Thailand or other countries, but a similar ITS sequence
      was detected in Micronesia, probably representing another undescribed Rasamsonia
      species. 

PMID- 24563834
TI  - Are alkalitolerant fungi of the Emericellopsis lineage (Bionectriaceae) of marine
      origin?
AB  - Surveying the fungi of alkaline soils in Siberia, Trans-Baikal regions (Russia),
      the Aral lake (Kazakhstan), and Eastern Mongolia, we report an abundance of
      alkalitolerant species representing the Emericellopsis-clade within the
      Acremonium cluster of fungi (order Hypocreales). On an alkaline medium (pH ca.
      10), 34 acremonium-like fungal strains were obtained. One of these was able to
      develop a sexual morph and was shown to be a new member of the genus
      Emericellopsis, described here as E. alkalina sp. nov. Previous studies showed
      two distinct ecological clades within Emericellopsis, one consisting of
      terrestrial isolates and one predominantly marine. Remarkably, all the isolates
      from our study sites show high phylogenetic similarity based on six loci (LSU and
      SSU rDNA, RPB2, TEF1-alpha, beta-tub and ITS region), regardless of their
      provenance within a broad geographical distribution. They group within the known
      marine-origin species, a finding that provides a possible link to the evolution
      of the alkaliphilic trait in the Emericellopsis lineage. We tested the capacities
      of all newly isolated strains, and the few available reference ex-type cultures,
      to grow over wide pH ranges. The growth performance varied among the tested
      isolates, which showed differences in growth rate as well as in pH preference.
      Whereas every newly isolated strain from soda soils was extremely alkalitolerant
      and displayed the ability to grow over a wide range of ambient pH (range 4-11.2),
      reference marine-borne and terrestrial strains showed moderate and no
      alkalitolerance, respectively. The growth pattern of the alkalitolerant
      Emericellopsis isolates was unlike that of the recently described and
      taxonomically unrelated alkaliphilic Sodiomyces alkalinus, obtained from the same
      type of soils but which showed a narrower preference towards high pH. 

PMID- 24563835
TI  - Xerochrysium gen. nov. and Bettsia, genera encompassing xerophilic species of
      Chrysosporium.
AB  - On the basis of a study of ITS sequences, Vidal et al. (Rev. Iber. Micol. 17: 22,
      2000) recommended that the genus Chrysosporium be restricted to species belonging
      to Onygenales. Using nrLSU genes, we studied the majority of clades examined by
      Vidal et al. and showed that currently accepted species in Chrysosporium
      phylogenetically belong in six clades in three orders. Surprisingly, the
      xerophilic species of Chrysosporium, long thought to be a single grouping away
      from the majority of Chrysosporium species, occupy two clades, one in Leotiales,
      the other in Eurotiales. Species accepted in Leotiales are related to the sexual
      genus Bettsia. One is the type species B. alvei, and related asexual strains
      classified as C. farinicola, the second is C. fastidium transferred to Bettsia as
      B. fastidia. Species in the Eurotiales are transferred to Xerochrysium gen. nov.,
      where the accepted species are X. xerophilum and X. dermatitidis, the correct
      name for C. inops on transfer to Xerochrysium. All accepted species are extreme
      xerophiles, found in dried and concentrated foods. 

PMID- 24563836
TI  - Septoglomus altomontanum, a new arbuscular mycorrhizal fungus from mountainous
      and alpine areas in Andalucia (southern Spain).
AB  - A new arbuscular mycorrhizal (AM) fungus was found in Sierra Nevada National Park
      of Andalucia (Southern Spain). It forms intraradical hyphae, vesicles and
      arbuscles, typical characteristics of Glomeromycetes. The spores are dark reddish
      brown to dark reddish black, 132-205 MUm diam, and are formed on pigmented
      subtending hyphae whose pores are regularly closed by a thick septum at the spore
      base but without support of introverted wall thickening. Phylogenetic analyses on
      concatenate sequences of the partial SSU, ITS region and the partial LSU of the
      rDNA confirm the new species, described here as Septoglomus altomontanum, in a
      monophyletic clade next to S. africanum. An identification key to all Septoglomus
      species described is given. The new fungus can unequivocally be distinguished
      from all other Septoglomus species by the combination of spore size, colour and
      spore wall structure, and especially by the shape and colour of the subtending
      hyphae. Septoglomus altomontanum has so far been found only in soils with pH 5.9
      6.7, located in mountainous and alpine altitudes (1800-3100 m asl) of Sierra
      Nevada which is well known for a high degree of plant endemism. While it is a
      frequent fungus in this area, it has so far not been found in lower altitudes in
      Andalucia. 

PMID- 24563837
TI  - Oospores of Pustula helianthicola in sunflower seeds and their role in the
      epidemiology of white blister rust.
AB  - White blister rust (WBR) of sunflower caused by Pustula helianthicola is an
      important and often underestimated disease in many countries of the world. The
      epidemiology of the pathogen is not yet fully understood; particularly the role
      of oospores in primary infection and long distance dispersal. We analysed WBR
      severity in sunflower under natural conditions and found disease incidence of 97
      99 % in fields where infected sunflower had first been observed ca. 8 yr ago.
      Besides the typical blisters of mitotic sporangia on leaves, large amounts of
      oospores were observed on the involucral bracts. Inoculation of sunflower
      seedlings with oospores from these bracts resulted in disease incidence of ca. 30
      %, thus confirming their infectivity without a period of dormancy. Bracts of
      infected flower heads from the field were checked for oospores using a binocular
      microscope and seeds were checked by light microscopy. Oospores were found in all
      of the bracts and in up to 28 % of the achenes. Light microscopy revealed that
      oospores developed in the thin-walled, crushed parenchymatic cells of the inner
      layer and in the parenchymatic rays of the fibrous layer of the pericarp. Dried
      seeds were grown in soil to assess the occurrence of seed borne infection. Within
      3 wk, up to 58 % of seedlings showed typical WBR pustules on cotyledons.
      Asymptomatic infections were confirmed in phenotypically healthy plants by using
      a PCR-based diagnostic test for P. helianthicola. The results showed the
      importance of oospores of P. helianthicola as the primary inoculum for WBR
      development in sunflower, and pointed to the potential role of contaminated seeds
      in the long distance transmission of the pathogen. 

PMID- 24563838
TI  - Research and teaching with the AFTOL SBD: an informatics resource for fungal
      subcellular and biochemical data.
AB  - The Structural and Biochemical Database (SBD), developed as part of the US NSF
      funded Assembling the Fungal Tree of Life (AFTOL), is a multi-investigator
      project. It is a major resource to present and manage morphological and
      biochemical information on Fungi and serves as a phyloinformatics tool for the
      scientific community. It also is an important resource for teaching mycology. The
      database, available at http://aftol.umn.edu, includes new and previously
      published subcellular data on Fungi, supplemented with images and literature
      links. Datasets automatically combined in NEXUS format from the site permit
      independent and combined (with molecular data) phylogenetic analyses. Character
      lists, a major feature of the site, serve as primary reference documents of
      subcellular and biochemical characters that distinguish taxa across the major
      fungal lineages. The character lists illustrated with images and drawings are
      informative for evolutionary and developmental biologists as well as educators,
      students and the public. Fungal Subcellular Ontology (FSO), developed as part of
      this effort is a primary initiative to provide a controlled vocabulary describing
      subcellular structures unique to Fungi. FSO establishes a full complement of
      terms that provide an operating ontological framework for the database. Examples
      are provided for using the database for teaching. 

PMID- 24563839
TI  - Cercosporoid fungi (Mycosphaerellaceae) 1. Species on other fungi, Pteridophyta
      and Gymnospermae.
AB  - Cercosporoid fungi (former Cercospora s. lat.) represent one of the largest
      groups of hyphomycetes belonging to the Mycosphaerellaceae (Ascomycota). They
      include asexual morphs, asexual holomorphs or species with mycosphaerella-like
      sexual morphs. Most of them are leaf-spotting plant pathogens with special
      phytopathological relevance. The only monograph of Cercospora s. lat., published
      by Chupp (1954), is badly in need of revision. However, the treatment of this
      huge group of fungi can only be accomplished stepwise on the basis of treatments
      of cercosporoid fungi on particular host plant families. The present first part
      of this series comprises an introduction, a survey on currently recognised
      cercosporoid genera, a key to the genera concerned, a discussion of taxonomically
      relevant characters, and descriptions and illustrations of cercosporoid species
      on other fungi (mycophylic taxa), Pteridophyta and Gymnospermae, arranged in
      alphabetical order under the particular cercosporoid genera, which are
      supplemented by keys to the species concerned. The following taxonomic novelties
      are introduced: Passalora austroplenckiae comb. nov., P. backmanii comb. nov., P.
      condensata comb. nov., P. gymnocladi comb. nov., P. thalictri comb. nov.,
      Pseudocercospora davalliicola sp. nov., P. chamaecyparidis comb. nov., P.
      cratevicola nom. nov., P. gleicheniae comb. nov., P. lygodiicola sp. nov., P.
      lygodiigena nom. nov., P. nephrolepidigena sp. nov., P. paraexosporioides sp.
      nov., P. pini-densiflorae var. montantiana comb. et stat. nov., P. pteridigena
      sp. nov., P. ptisanae sp. nov., P. sciadopityos sp. nov., P. subramanianii nom.
      nov., P. thujina comb. nov., and Zasmidium australiense comb. nov. 

PMID- 24563840
TI  - Astraeus: hidden dimensions.
AB  - The genus Astraeus is shown to be even more complex than recent studies have
      found. There are problems defining what the molecular fingerprint is of the
      generic type species. The present article, based on molecular and morphological
      information and the classical literature, attempts to throw further light on
      these important ectomycorrhizal fungi. Our studies go part way in an endeavour to
      unravel the taxonomy and systematics of this genus, necessitating the recognition
      of at least three new species. Potential nomenclatural problems are also
      outlined. 

PMID- 24563841
TI  - IMA Genome-F 1: Ceratocystis fimbriata: Draft nuclear genome sequence for the
      plant pathogen, Ceratocystis fimbriata.
AB  - The draft nuclear genome of Ceratocystis fimbriata, the type species of
      Ceratocystis, is comprised of 29 410 862 bp. De novo gene prediction produced 7
      266 genes, which is low for an ascomycete fungus. The availability of the genome
      provides opportunities to study aspects of the biology of this and other
      Ceratocystis species. 

PMID- 24563842
TI  - Two new species of hydnoid-fungi from India.
AB  - Two taxa, Hericium yumthangense (Russulales, Agaricomycotina) and
      Mycoleptodonoides sharmae (Polyporales, Agaricomycotina) are described as new to
      science from the Shingba Rhododendron sanctuary located in the northern district
      of Sikkim, India. Macro- and micromorphological characters are described and
      illustrated for both species, which are compared with allied taxa. ITS rDNA
      sequences supported H. yumthangense as a rather isolated species within Hericium,
      the species complexes of which were not resolved due to low interspecific
      sequence divergence. In the case of M. sharmae, 28S rDNA (D1/D2) data rendered
      this poorly known genus among well-known taxa of the core-polyporoid clade. 

PMID- 24563844
TI  - A without-prejudice list of generic names of fungi for protection under the
      International Code of Nomenclature for algae, fungi, and plants.
AB  - As a first step towards the production of a List of Protected Generic Names for
      Fungi, a without-prejudice list is presented here as a basis for future
      discussion and the production of a List for formal adoption. We include 6995
      generic names out of the 17072 validly published names proposed for fungi and
      invite comments from all interested mycologists by 31 March 2014. The selection
      of names for inclusion takes note of recent major publications on different
      groups of fungi, and further the decisions reached so far by international
      working groups concerned with particular families or genera. Changes will be
      sought in the Code to provide for this and lists at other ranks to be protected
      against any competing unlisted names, and to permit the inclusion of names of
      lichen-forming fungi. A revised draft will be made available for further
      discussion at the 10(th) International Mycological Congress in Bangkok in August
      2014. A schedule is suggested for the steps needed to produce a list for adoption
      by the International Botanical Congress in August 2017. This initiative provides
      mycologists with an opportunity to place nomenclature at the generic level on a
      more secure and stable base. 

PMID- 24563843
TI  - MycoBank gearing up for new horizons.
AB  - MycoBank, a registration system for fungi established in 2004 to capture all
      taxonomic novelties, acts as a coordination hub between repositories such as
      Index Fungorum and Fungal Names. Since January 2013, registration of fungal names
      is a mandatory requirement for valid publication under the International Code of
      Nomenclature for algae, fungi and plants (ICN). This review explains the database
      innovations that have been implemented over the past few years, and discusses new
      features such as advanced queries, registration of typification events (MBT
      numbers for lecto, epi- and neotypes), the multi-lingual database interface, the
      nomenclature discussion forum, annotation system, and web services with links to
      third parties. MycoBank has also introduced novel identification services,
      linking DNA sequence data to numerous related databases to enable intelligent
      search queries. Although MycoBank fills an important void for taxon registration,
      challenges for the future remain to improve links between taxonomic names and DNA
      data, and to also introduce a formal system for naming fungi known from DNA
      sequence data only. To further improve the quality of MycoBank data, remote
      access will now allow registered mycologists to act as MycoBank curators, using
      Citrix software. 

PMID- 24563845
TI  - Developing self-regulation in early childhood.
AB  - Studies using fMRI at rest and during task performance have revealed a set of
      brain areas and their connections that can be linked to the ability of children
      to regulate their thoughts, actions and emotions. Higher self-regulation has also
      been related favorable outcomes in adulthood. These findings have set the
      occasion for methods of improving self-regulation via training. A tool kit of
      such methods is now available. It remains to be seen if educators will use these
      new findings and tools to forge practical methods for improving the lives of the
      world's children.

PMID- 24563847
TI  - A mitochondrially targeted compound delays aging in yeast through a mechanism
      linking mitochondrial membrane lipid metabolism to mitochondrial redox biology.
AB  - A recent study revealed a mechanism of delaying aging in yeast by a natural
      compound which specifically impacts mitochondrial redox processes. In this
      mechanism, exogenously added lithocholic bile acid enters yeast cells,
      accumulates mainly in the inner mitochondrial membrane, and elicits an age
      related remodeling of phospholipid synthesis and movement within both
      mitochondrial membranes. Such remodeling of mitochondrial phospholipid dynamics
      progresses with the chronological age of a yeast cell and ultimately causes
      significant changes in mitochondrial membrane lipidome. These changes in the
      composition of membrane phospholipids alter mitochondrial abundance and
      morphology, thereby triggering changes in the age-related chronology of such
      longevity-defining redox processes as mitochondrial respiration, the maintenance
      of mitochondrial membrane potential, the preservation of cellular homeostasis of
      mitochondrially produced reactive oxygen species, and the coupling of electron
      transport to ATP synthesis. 

PMID- 24563846
TI  - Dietary restriction in cerebral bioenergetics and redox state.
AB  - The brain has a central role in the regulation of energy stability of the
      organism. It is the organ with the highest energetic demands, the most
      susceptible to energy deficits, and is responsible for coordinating behavioral
      and physiological responses related to food foraging and intake. Dietary
      interventions have been shown to be a very effective means to extend lifespan and
      delay the appearance of age-related pathological conditions, notably those
      associated with brain functional decline. The present review focuses on the
      effects of these interventions on brain metabolism and cerebral redox state, and
      summarizes the current literature dealing with dietary interventions on brain
      pathology. 

PMID- 24563848
TI  - Catalase activity is stimulated by H(2)O(2) in rich culture medium and is
      required for H(2)O(2) resistance and adaptation in yeast.
AB  - Catalases are efficient scavengers of H2O2 and protect cells against H2O2 stress.
      Examination of the H2O2 stimulon in Saccharomyces cerevisiae revealed that the
      cytosolic catalase T (Ctt1) protein level increases 15-fold on H2O2 challenge in
      synthetic complete media although previous work revealed that deletion of the
      CCT1 or CTA1 genes (encoding peroxisomal/mitochondrial catalase A) does not
      increase the H2O2 sensitivity of yeast challenged in phosphate buffer (pH 7.4).
      This we attributed to our observation that catalase activity is depressed when
      yeast are challenged with H2O2 in nutrient-poor media. Hence, we performed a
      systematic comparison of catalase activity and cell viability of wild-type yeast
      and of the single catalase knockouts, ctt1? and cta1?, following H2O2 challenge
      in nutrient-rich medium (YPD) and in phosphate buffer (pH 7.4). Ctt1 but not Cta1
      activity is strongly induced by H2O2 when cells are challenged in YPD but
      suppressed when cells are challenged in buffer. Consistent with the activity
      results, exponentially growing ctt1? cells in YPD are more sensitive to H2O2 than
      wild-type or cta1? cells, whereas in buffer all three strains exhibit comparable
      H2O2 hypersensitivity. Furthermore, catalase activity is increased during
      adaptation to sublethal H2O2 concentrations in YPD but not in buffer. We conclude
      that induction of cytosolic Ctt1 activity is vital in protecting yeast against
      exogenous H2O2 but this activity is inhibited by H2O2 when cells are challenged
      in nutrient-free media. 

PMID- 24563849
TI  - Inhibition of extracellular HMGB1 attenuates hyperoxia-induced inflammatory acute
      lung injury.
AB  - Prolonged exposure to hyperoxia results in acute lung injury (ALI), accompanied
      by a significant elevation in the levels of proinflammatory cytokines and
      leukocyte infiltration in the lungs. However, the mechanisms underlying hyperoxia
      induced proinflammatory ALI remain to be elucidated. In this study, we
      investigated the role of the proinflammatory cytokine high mobility group box
      protein 1 (HMGB1) in hyperoxic inflammatory lung injury, using an adult mouse
      model. The exposure of C57BL/6 mice to >=99% O2 (hyperoxia) significantly
      increased the accumulation of HMGB1 in the bronchoalveolar lavage fluids (BALF)
      prior to the onset of severe inflammatory lung injury. In the airways of
      hyperoxic mice, HMGB1 was hyperacetylated and existed in various redox forms.
      Intratracheal administration of recombinant HMGB1 (rHMGB1) caused a significant
      increase in leukocyte infiltration into the lungs compared to animal treated with
      a non-specific peptide. Neutralizing anti-HMGB1 antibodies, administrated before
      hyperoxia significantly attenuated pulmonary edema and inflammatory responses, as
      indicated by decreased total protein content, wet/dry weight ratio, and numbers
      of leukocytes in the airways. This protection was also observed when HMGB1
      inhibitors were administered after the onset of the hyperoxic exposure. The
      aliphatic antioxidant, ethyl pyruvate (EP), inhibited HMGB1 secretion from
      hyperoxic macrophages and attenuated hyperoxic lung injury. Overall, our data
      suggest that HMGB1 plays a critical role in mediating hyperoxic ALI through the
      recruitment of leukocytes into the lungs. If these results can be translated to
      humans, they suggest that HMGB1 inhibitors provide treatment regimens for
      oxidative inflammatory lung injury in patients receiving hyperoxia through
      mechanical ventilation. 

PMID- 24563853
TI  - Redox biology: interface of the exposome with the proteome, epigenome and genome.
AB  - The exposome is the cumulative measure of environmental influences and associated
      biological responses throughout lifespan, including exposures from the
      environment, diet, behavior and endogenous processes. Much of the direct
      interaction of an individual's exposome involves redox biology as the body
      responds to environmental, dietary and behavioral risk factors of disease. The
      present commentary addresses this critical interface and the need for redox
      biologists to lead development of concepts and strategies to sequence the
      exposome. 

PMID- 24563852
TI  - Peroxynitrite induced mitochondrial biogenesis following MnSOD knockdown in
      normal rat kidney (NRK) cells.
AB  - Superoxide is widely regarded as the primary reactive oxygen species (ROS) which
      initiates downstream oxidative stress. Increased oxidative stress contributes, in
      part, to many disease conditions such as cancer, atherosclerosis,
      ischemia/reperfusion, diabetes, aging, and neurodegeneration. Manganese
      superoxide dismutase (MnSOD) catalyzes the dismutation of superoxide into
      hydrogen peroxide which can then be further detoxified by other antioxidant
      enzymes. MnSOD is critical in maintaining the normal function of mitochondria,
      thus its inactivation is thought to lead to compromised mitochondria. Previously,
      our laboratory observed increased mitochondrial biogenesis in a novel kidney
      specific MnSOD knockout mouse. The current study used transient siRNA mediated
      MnSOD knockdown of normal rat kidney (NRK) cells as the in vitro model, and
      confirmed functional mitochondrial biogenesis evidenced by increased PGC1alpha
      expression, mitochondrial DNA copy numbers and integrity, electron transport
      chain protein CORE II, mitochondrial mass, oxygen consumption rate, and overall
      ATP production. Further mechanistic studies using mitoquinone (MitoQ), a
      mitochondria-targeted antioxidant and L-NAME, a nitric oxide synthase (NOS)
      inhibitor demonstrated that peroxynitrite (at low micromolar levels) induced
      mitochondrial biogenesis. These findings provide the first evidence that low
      levels of peroxynitrite can initiate a protective signaling cascade involving
      mitochondrial biogenesis which may help to restore mitochondrial function
      following transient MnSOD inactivation. 

PMID- 24563850
TI  - Molecular chaperones and proteostasis regulation during redox imbalance.
AB  - Free radicals originate from both exogenous environmental sources and as by
      products of the respiratory chain and cellular oxygen metabolism. Sustained
      accumulation of free radicals, beyond a physiological level, induces oxidative
      stress that is harmful for the cellular homeodynamics as it promotes the
      oxidative damage and stochastic modification of all cellular biomolecules
      including proteins. In relation to proteome stability and maintenance, the
      increased concentration of oxidants disrupts the functionality of cellular
      protein machines resulting eventually in proteotoxic stress and the deregulation
      of the proteostasis (homeostasis of the proteome) network (PN). PN curates the
      proteome in the various cellular compartments and the extracellular milieu by
      modulating protein synthesis and protein machines assembly, protein recycling and
      stress responses, as well as refolding or degradation of damaged proteins.
      Molecular chaperones are key players of the PN since they facilitate folding of
      nascent polypeptides, as well as holding, folding, and/or degradation of
      unfolded, misfolded, or non-native proteins. Therefore, the expression and the
      activity of the molecular chaperones are tightly regulated at both the
      transcriptional and post-translational level at organismal states of increased
      oxidative and, consequently, proteotoxic stress, including ageing and various age
      related diseases (e.g. degenerative diseases and cancer). In the current review
      we present a synopsis of the various classes of intra- and extracellular
      chaperones, the effects of oxidants on cellular homeodynamics and diseases and
      the redox regulation of chaperones. 

PMID- 24563851
TI  - The ubiquitin proteasome system in Caenorhabditis elegans and its regulation.
AB  - Protein degradation constitutes a major cellular function that is responsible for
      maintenance of the normal cellular physiology either through the degradation of
      normal proteins or through the elimination of damaged proteins. The Ubiquitin
      Proteasome System (UPS)(1) is one of the main proteolytic systems that
      orchestrate protein degradation. Given that up- and down- regulation of the UPS
      system has been shown to occur in various normal (such as ageing) and
      pathological (such as neurodegenerative diseases) processes, the exogenous
      modulation of the UPS function and activity holds promise of (a) developing new
      therapeutic interventions against various diseases and (b) establishing
      strategies to maintain cellular homeostasis. Since the proteasome genes are
      evolutionarily conserved, their role can be dissected in simple model organisms,
      such as the nematode, Caenorhabditis elegans. In this review, we survey findings
      on the redox regulation of the UPS in C. elegans showing that the nematode is an
      instrumental tool in the identification of major players in the UPS pathway.
      Moreover, we specifically discuss UPS-related genes that have been modulated in
      the nematode and in human cells and have resulted in similar effects thus further
      exhibiting the value of this model in the study of the UPS. 

PMID- 24563854
TI  - Prenatal vitamin C deficiency results in differential levels of oxidative stress
      during late gestation in foetal guinea pig brains.
AB  - Antioxidant defences are comparatively low during foetal development making the
      brain particularly susceptible to oxidative stress during antioxidant
      deficiencies. The brain is one of the organs containing the highest concentration
      of vitamin C (VitC) and VitC deficiency during foetal development may place the
      brain at risk of redox status imbalance. In the present study, we investigated
      the developmental pattern and effect of VitC deficiency on antioxidants, vitamin
      E and superoxide dismutase (SOD), assessed oxidative damage by measuring
      malondialdehyde (MDA), hydroxynonenal (HNE) and nitrotyrosine (NT) and analysed
      gene and protein expression of apoptosis marker caspase-3 in the guinea pig
      foetal brain at two gestational (GD) time points, GD 45/pre-term and GD 56/near
      term following either a VitC sufficient (CTRL) or deficient (DEF) maternal
      dietary regime. We show that except for SOD, antioxidants and oxidative damage
      markers are differentially expressed between the two GDs, with high VitC
      (p<0.0001), NT modified proteins (p<0.0001) and active caspase-3 levels (p<0.05)
      at pre-term and high vitamin E levels (p<0.0001), HNE (p<0.0001) and MDA
      (p<0.0001) at near term. VitC deficiency significantly increased SOD activity
      (p<0.0001) compared to CTRLs at both GDs indicating a compensatory response,
      however, low levels of VitC significantly elevated MDA levels (p<0.05) in DEF at
      near term. Our results show a differential regulation of the investigated markers
      during late gestation and suggest that immature brains are susceptible to
      oxidative stress due to prenatal vitC deficiency in spite of an induction of
      protective adaptation mechanisms. 

PMID- 24563855
TI  - Optogenetic control of ROS production.
AB  - Reactive Oxygen Species (ROS) are known to cause oxidative damage to DNA,
      proteins and lipids. In addition, recent evidence suggests that ROS can also
      initiate signaling cascades that respond to stress and modify specific redox
      sensitive moieties as a regulatory mechanism. This suggests that ROS are
      physiologically-relevant signaling molecules. However, these sensor/effector
      molecules are not uniformly distributed throughout the cell. Moreover, localized
      ROS damage may elicit site-specific compensatory measures. Thus, the impact of
      ROS can be likened to that of calcium, a ubiquitous second messenger, leading to
      the prediction that their effects are exquisitely dependent upon their location,
      quantity and even the timing of generation. Despite this prediction, ROS
      signaling is most commonly intuited through the global administration of
      chemicals that produce ROS or by ROS quenching through global application of
      antioxidants. Optogenetics, which uses light to control the activity of
      genetically-encoded effector proteins, provides a means of circumventing this
      limitation. Photo-inducible genetically-encoded ROS-generating proteins (RGPs)
      were originally employed for their phototoxic effects and cell ablation. However,
      reducing irradiance and/or fluence can achieve sub-lethal levels of ROS that may
      mediate subtle signaling effects. Hence, transgenic expression of RGPs as fusions
      to native proteins gives researchers a new tool to exert spatial and temporal
      control over ROS production. This review will focus on the new frontier defined
      by the experimental use of RGPs to study ROS signaling. 

PMID- 24563856
TI  - Acetaminophen-induced liver damage in mice is associated with gender-specific
      adduction of peroxiredoxin-6.
AB  - The mechanism by which acetaminophen (APAP) causes liver damage evokes many
      aspects drug metabolism, oxidative chemistry, and genetic-predisposition. In this
      study, we leverage the relative resistance of female C57BL/6 mice to APAP-induced
      liver damage (AILD) compared to male C57BL/6 mice in order to identify the
      cause(s) of sensitivity. Furthermore, we use mice that are either heterozygous
      (HZ) or null (KO) for glutamate cysteine ligase modifier subunit (Gclm), in order
      to titrate the toxicity relative to wild-type (WT) mice. Gclm is important for
      efficient de novo synthesis of glutathione (GSH). APAP (300 mg/kg, ip) or saline
      was administered and mice were collected at 0, 0.5, 1, 2, 6, 12, and 24 h. Male
      mice showed marked elevation in serum alanine aminotransferase by 6 h. In
      contrast, female WT and HZ mice showed minimal toxicity at all time points.
      Female KO mice, however, showed AILD comparable to male mice. Genotype-matched
      male and female mice showed comparable APAP-protein adducts, with Gclm KO mice
      sustaining significantly greater adducts. ATP was depleted in mice showing
      toxicity, suggesting impaired mitochondria function. Indeed, peroxiredoxin-6, a
      GSH-dependent peroxiredoxin, was preferentially adducted by APAP in mitochondria
      of male mice but rarely adducted in female mice. These results support parallel
      mechanisms of toxicity where APAP adduction of peroxiredoxin-6 and sustained GSH
      depletion results in the collapse of mitochondria function and hepatocyte death.
      We conclude that adduction of peroxiredoxin-6 sensitizes male C57BL/6 mice to
      toxicity by acetaminophen. 

PMID- 24563857
TI  - The proteasome and the degradation of oxidized proteins: part III-Redox
      regulation of the proteasomal system.
AB  - Here, we review shortly the current knowledge on the regulation of the
      proteasomal system during and after oxidative stress. After addressing the
      components of the proteasomal system and the degradation of oxidatively damaged
      proteins in part I and II of this series, we address here which changes in
      activity undergo the proteasome and the ubiquitin-proteasomal system itself under
      oxidative conditions. While several components of the proteasomal system undergo
      direct oxidative modification, a number of redox-regulated events are modulating
      the proteasomal activity in a way it can address the major tasks in an oxidative
      stress situation: the removal of oxidized proteins and the adaptation of the
      cellular metabolism to the stress situation. 

PMID- 24563859
TI  - A comparison between passive and active case finding in TB control in the
      Arkhangelsk region.
AB  - BACKGROUND: In Russia, active case finding (ACF) for certain population groups
      has been practiced uninterruptedly for many decades, but no studies comparing ACF
      and passive case finding (PCF) approaches in Russia have been published.
      OBJECTIVE: The aim of this study was to describe the main differences in symptoms
      and diagnostic delay between patients who come to TB services through PCF and ACF
      strategies. METHODS: A cross-sectional study was conducted among 453 new
      pulmonary tuberculosis (PTB) patients, who met criteria of TB diagnostic delay in
      Arkhangelsk. RESULTS: ACF patients used self-treatment more often than PCF
      patients (90.1% vs. 24.6%) and 36.3% of them were alcohol abusers (as opposed to
      only 26.2% of PCF patients). The median patient delay (PD) in PCF was 4 weeks,
      IQR (1-8 weeks), and less than 1 week in ACF. Twenty-three per cent of the PCF
      patients were seen by a medical provider within the first week of their illness
      onset. CONCLUSION: Patients diagnosed through ACF tended to under-report their TB
      symptoms and showed low attention to their own health. However, ACF allowed for
      discovering TB patients earlier than PCF, and this was also the case for alcohol
      abusing patients. PCF systems should be supplemented with ACF strategies.

PMID- 24563858
TI  - Thiol-based H2O2 signalling in microbial systems.
AB  - Cysteine residues, and in particular their thiolate groups, react not only with
      reactive oxygen species but also with electrophiles and with reactive nitrogen
      species. Thus, cysteine oxidation has often been linked to the toxic effects of
      some of these reactive molecules. However, thiol-based switches are common in
      protein sensors of antioxidant cascades, in both prokaryotic and eukaryotic
      organisms. We will describe here three redox sensors, the transcription factors
      OxyR, Yap1 and Pap1, which respond by disulfide bond formation to hydrogen
      peroxide stress, focusing specially on the differences among the three peroxide
      sensing mechanisms. 

PMID- 24563860
TI  - A novel platelet concentrate: titanium-prepared platelet-rich fibrin.
AB  - We developed a new product called titanium-prepared platelet-rich fibrin (T-PRF).
      The T-PRF method is based on the hypothesis that titanium may be more effective
      in activating platelets than the silica activators used with glass tubes in
      Chouckroun's leukocyte- and platelet-rich fibrin (L-PRF) method. In this study,
      we aimed to define the structural characteristics of T-PRF and compare it with L
      PRF. Blood samples were collected from 10 healthy male volunteers. The blood
      samples were drawn using a syringe. Nine milliliters was transferred to a dry
      glass tube, and 9 mL was transferred to a titanium tube. Half of each clot (i.e.,
      the blood that was clotted using T-PRF or L-PRF) was processed with a scanning
      electron microscope (SEM). The other half of each clot was processed for
      fluorescence microscopy analysis and light microscopy analysis. The T-PRF samples
      seemed to have a highly organized network with continuous integrity compared to
      the other L-PRF samples. Histomorphometric analysis showed that T-PRF fibrin
      network covers larger area than L-PRF fibrin network; also fibrin seemed thicker
      in the T-PRF samples. This is the first human study to define T-PRF as an
      autogenous leukocyte- and platelet-rich fibrin product. The platelet activation
      by titanium seems to offer some high characteristics to T-PRF. 

PMID- 24563861
TI  - Investigation of the effects of preoperative hydration on the postoperative
      nausea and vomiting.
AB  - INTRODUCTION: Postoperative nausea and vomiting (PONV) after laparoscopic
      cholecystectomy operations still continue to be a serious problem. Intravenous
      fluid administration has been shown to reduce PONV. Some patients have higher
      risk for PONV described by APFEL score. In this study, our aim was to determine
      the effects of preoperative intravenous hydration on postoperative nausea and
      vomiting in high Apfel scored patients undergoing laparoscopic cholecystectomy
      surgery. PATIENTS AND METHODS: This study is performed with 50 female patients
      who had APFEL score 3-4 after ethics committee approval and informed consent was
      taken from patients. The patients were divided into 2 groups: group 1 (P1):
      propofol + preoperative hydration and group 2 (P2): propofol + no preoperative
      hydration. RESULTS: When the total nausea VAS scores of groups P1 and P2 to which
      hydration was given or not given were compared, a statistically significant
      difference was detected at 8th and 12th hours (P = 0.001 and P = 0.041). It was
      observed that in group P1, which was given hydration, the nausea VAS score was
      lower. When the total number of patients who had nausea and vomiting in P1 and
      P2, more patients suffered nausea in P2 group. DISCUSSION: Preoperative hydration
      may be effective in high Apfel scored patients to prevent postoperative nausea.

PMID- 24563862
TI  - Routine follow-up cranial computed tomography for deeply sedated, intubated, and
      ventilated multiple trauma patients with suspected severe head injury.
AB  - BACKGROUND: Missed or delayed detection of progressive neuronal damage after
      traumatic brain injury (TBI) may have negative impact on the outcome. We
      investigated whether routine follow-up CT is beneficial in sedated and
      mechanically ventilated trauma patients. METHODS: The study design is a
      retrospective chart review. A routine follow-up cCT was performed 6 hours after
      the admission scan. We defined 2 groups of patients, group I: patients with equal
      or recurrent pathologies and group II: patients with new findings or progression
      of known pathologies. RESULTS: A progression of intracranial injury was found in
      63 patients (42%) and 18 patients (12%) had new findings in cCT 2 (group II). In
      group II a change in therapy was found in 44 out of 81 patients (54%). 55
      patients with progression or new findings on the second cCT had no clinical signs
      of neurological deterioration. Of those 24 patients (44%) had therapeutic
      consequences due to the results of the follow-up cCT. CONCLUSION: We found new
      diagnosis or progression of intracranial pathology in 54% of the patients. In 54%
      of patients with new findings and progression of pathology, therapy was changed
      due to the results of follow-up cCT. In trauma patients who are sedated and
      ventilated for different reasons a routine follow-up CT is beneficial.

PMID- 24563863
TI  - Notch1 and 4 signaling responds to an increasing vascular wall shear stress in a
      rat model of arteriovenous malformations.
AB  - Notch signaling is suggested to promote the development and maintenance of
      cerebral arteriovenous malformations (AVMs), and an increasing wall shear stress
      (WSS) contributes to AVM rupture. Little is known about whether WSS impacts Notch
      signaling, which is important for understanding the angiogenesis of AVMs. WSS was
      measured in arteriovenous fistulas (AVF) surgically created in 96 rats at
      different time points over a period of 84 days. The expression of Notch receptors
      1 and 4 and their ligands, Delta1 and 4, Jagged1, and Notch downstream gene
      target Hes1 was quantified in "nidus" vessels. The interaction events between
      Notch receptors and their ligands were quantified using proximity ligation assay.
      There was a positive correlation between WSS and time (r = 0.97; P < 0.001). The
      expression of Notch receptors and their ligands was upregulated following AVF
      formation. There was a positive correlation between time and the number of
      interactions between Notch receptors and their ligands aftre AVF formation (r =
      0.62, P < 0.05) and a positive correlation between WSS and the number of
      interactions between Notch receptors and their ligands (r = 0.87, P < 0.005). In
      conclusion, an increasing WSS may contribute to the angiogenesis of AVMs by
      activation of Notch signaling. 

PMID- 24563864
TI  - Direct cell-cell contact between mesenchymal stem cells and endothelial
      progenitor cells induces a pericyte-like phenotype in vitro.
AB  - Tissue engineering techniques for the regeneration of large bone defects require
      sufficient vascularisation of the applied constructs to ensure a sufficient
      supply of oxygen and nutrients. In our previous work, prevascularised 3D
      scaffolds have been successfully established by coculture of bone marrow derived
      stem cells (MSCs) and endothelial progenitor cells (EPCs). We identified
      stabilising pericytes (PCs) as part of newly formed capillary-like structures. In
      the present study, we report preliminary data on the interactions between MSCs
      and EPCs, leading to the differentiation of pericyte-like cells. MSCs and EPCs
      were seeded in transwell cultures, direct cocultures, and single cultures. Cells
      were cultured for 10 days in IMDM 10% FCS or IMDM 5% FCS 5% platelet lysate
      medium. Gene expression of PC markers, CD146, NG2, alphaSMA, and PDGFR-beta, was
      analysed using RT-PCR at days 0, 3, 7, and 10. The upregulation of CD146, NG2,
      and alphaSMA in MSCs in direct coculture with EPCs advocates the MSCs'
      differentiation towards a pericyte-like phenotype in vitro. These results suggest
      that pericyte-like cells derive from MSCs and that cell-cell contact with EPCs is
      an important factor for this differentiation process. These findings emphasise
      the concept of coculture strategies to promote angiogenesis for cell-based tissue
      engineered bone grafts.

PMID- 24563865
TI  - Hormonal contraceptive use and the prevalence of endometriotic lesions at
      different regions within the peritoneal cavity.
AB  - Endometriosis is an estrogen-dependent disease that can lead to chronic pain and
      subfertility. Endometriotic lesions found in different locations are
      heterogeneous and may represent a collection of related but distinct conditions.
      Whether there is a relationship between hormonal contraceptive (HC) use and
      endometriosis is still controversial. The purpose of this study was to determine
      whether HC use affected the prevalence of endometriotic lesions differently based
      on lesion location. Data was retrospectively collected from 161 patients
      presenting to the Berne University Women's Hospital between 2008 and 2012 for
      laparoscopic investigation. Women with histologically proven endometriosis were
      included in the study and patients were grouped according to lesion location and
      HC use. The results of the study indicate that HC users are significantly less
      likely to have endometriotic lesions on the ovaries, although in contrast, no
      difference was observed in the incidence of lesions in the rectovaginal septum
      (RVS) or peritoneal region. In addition, women using HC who were diagnosed with
      endometriotic lesions on the peritoneum were significantly younger than women
      with lesions in other locations. In conclusion, women with endometriosis who are
      currently using HC are less likely to have ovarian endometriotic lesions than in
      alternate locations. 

PMID- 24563866
TI  - Variables associated with the use of coercive measures on psychiatric patients in
      Spanish penitentiary centers.
AB  - We have studied the use of coercive medical measures (forced medication,
      isolation, and mechanical restraint) in mentally ill inmates within two secure
      psychiatric hospitals (SPH) and three regular prisons (RP) in Spain. Variables
      related to adopted coercive measures were analyzed, such as type of measure,
      causes of indication, opinion of patient inmate, opinion of medical staff, and
      more frequent morbidity. A total of 209 patients (108 from SPH and 101 from RP)
      were studied. Isolation (41.35%) was the most frequent coercive measure, followed
      by mechanical restraint (33.17%) and forced medication (25.48%). The type of
      center has some influence; specifically in RP there is less risk of isolation and
      restraint than in SPH. Not having had any previous imprisonment reduces isolation
      and restraint risk while increases the risk of forced medication, as well as
      previous admissions to psychiatric inpatient units does. Finally, the fact of
      having lived with a partner before imprisonment reduces the risk of forced
      medication and communication with the family decreases the risk of isolation.
      Patients subjected to a coercive measure exhibited a pronounced psychopathology
      and most of them had been subjected to such measures on previous occasions. The
      mere fact of external assessment of compliance with human rights slows down the
      incidence of coercive measures. 

PMID- 24563867
TI  - Evaluation of buspirone on streptozotocin induced type 1 diabetes and its
      associated complications.
AB  - We have evaluated the effect of buspirone (1.5 mg/kg/day, p.o.) type 1 diabetes
      induced cardiovascular complications induced by streptozotocin (STZ, 45 mg/kg,
      i.v.) in Wistar rats. Various biochemical, cardiovascular, and hemodynamic
      parameters were measured at the end of 8 weeks of treatment. STZ produced
      significant hyperglycaemia, hypoinsulinemia, and dyslipidemia, which was
      prevented by buspirone treatment. STZ produced increase in serum creatinine,
      urea, lactate dehydrogenase, creatinine kinase, and C-reactive protein levels and
      treatment with buspirone produced reduction in these levels. STZ produced
      increase in cardiac and LV hypertrophy index, LV/RV ratio, and LV collagen, which
      were decreased by buspirone treatment. Buspirone also prevented STZ induced
      hemodynamic alterations and oxidative stress. These results were further
      supported by histopathological studies in which buspirone showed marked reduction
      in fibrosis and cardiac fiber disarray. In conclusion, our data suggests that
      buspirone is beneficial as an antidiabetic agent in type 1 diabetes mellitus and
      also prevents its cardiac complications. 

PMID- 24563868
TI  - Determinants of noninvasive ventilation outcomes during an episode of acute
      hypercapnic respiratory failure in chronic obstructive pulmonary disease: the
      effects of comorbidities and causes of respiratory failure.
AB  - OBJECTIVES: To investigate the effect of the cause of acute respiratory failure
      and the role of comorbidities both acute and chronic on the outcome of COPD
      patients admitted to Respiratory Intensive Care Unit (RICU) with acute
      respiratory failure and treated with NIV. DESIGN: Observational prospective
      study. PATIENTS AND METHODS: 176 COPD patients consecutively admitted to our RICU
      over a period of 3 years and treated with NIV were evaluated. In all patients
      demographic, clinical, and functional parameters were recorded including the
      cause of acute respiratory failure, SAPS II score, Charlson comorbidity index,
      and further comorbidities not listed in the Charlson index. NIV success was
      defined as clinical improvement leading to discharge to regular ward, while
      exitus or need for endotracheal intubation was considered failure. RESULTS: NIV
      outcome was successful in 134 patients while 42 underwent failure. Univariate
      analysis showed significantly higher SAP II score, Charlson index, prevalence of
      pneumonia, and lower serum albumin level in the failure group. Multivariate
      analysis confirmed a significant predictive value for pneumonia and albumin.
      CONCLUSIONS: The most important determinants of NIV outcome in COPD patients are
      the presence of pneumonia and the level of serum albumin as an indicator of the
      patient nutritional status.

PMID- 24563870
TI  - An abscopal response to radiation and ipilimumab in a patient with metastatic non
      small cell lung cancer.
AB  - A posteriori evidence suggests that radiotherapy to a targeted tumor can elicit
      an immune-mediated abscopal (ab-scopus, away from the target) effect in non
      targeted tumors, when combined with an anti-cytotoxic T-lymphocyte antigen-4
      monoclonal (CTLA-4) antibody. Concurrent radiotherapy and ipilimumab (a human
      monoclonal anti-CTLA-4 antibody) induced immune-mediated abscopal effects in
      poorly immunogenic pre-clinical tumor models and metastatic melanoma patients.
      However, no such reports exist for patients with metastatic lung adenocarcinoma.
      We report the first abscopal response in a treatment-refractory lung cancer
      patient treated with radiotherapy and ipilimumab. A post-treatment increase in
      tumor-infiltrating cytotoxic lymphocytes, tumor regression, and normalization of
      tumor markers was observed. One year after treatment with concurrent radiotherapy
      and ipilimumab the patient is without evidence of disease. 

PMID- 24563873
TI  - The timeless influence of Hippocratic ideals on diet, salicytates and
      personalized medicine.
AB  - At a time when superstition and deities were thought to be responsible for health
      and disease, Hippocrates of Kos emerged as a rational thinker assigning disease
      to natural causes. His insights, which principally arose from what may be
      considered almost compulsive examination and comparison, formed the basis of
      Hippocratic Medicine. There are still unresolved questions regarding the
      authenticity of the approximately 70 works shaping the Hippocratic Corpus.
      Assigning authorship precisely presents difficulties and given that the various
      treatises in the collection appear to span a period of between 100 and 300 years,
      it is clear that they may not be ascribed to a single author. Ancient
      commentaries, including translation and annotation by the Hellenic physician
      Galen and more recently by Emile Littre have helped preserve and structure our
      knowledge of Hippocratic ideals. Further, a large school of contemporary scholars
      are constantly refining our understanding. Despite the controversies and
      uncertainties, the underlying themes of Hippocrates' influence on medicine which
      involve meticulous observation, comparison, prognosis and prediction are evident.
      Importantly, the Hippocratic Oath remains a masterpiece of medical morals and
      ethics, analogous forms of which are still used today. Indeed, the Hippocratic
      Corpus teaches timeless concepts which do not only relate to medical thought and
      methodology but also to the more gentle aspects of the art. In this essay
      Hippocratic observations are considered in relation to three important matters
      preoccupying modern medicine: a) nutrition, b) drug development and c)
      personalized medicine. 

PMID- 24563872
TI  - Cardiac Function and Short-Term Outcome in Patients with Acute Ischemic Stroke: A
      Cross-Sectional Study.
AB  - Few studies have investigated the relationship between left ventricular ejection
      fraction (LVEF) and functional outcome in ischemic stroke patients. The purpose
      of this study was to determine if a low LVEF in ischemic stroke was associated
      with functional outcome. A cross-sectional study was performed on ischemic stroke
      patients admitted to a single academic stroke center from June 2008 to December
      2010. LVEF was determined using transthoracic or transesophageal
      echocardiography. Patients were categorized into three LVEF groups: severely low
      (<30%), moderately low (30-49%), and normal (>50%). Baseline demographics, in
      hospital complications, and early outcomes were compared among LVEF groups using
      Chi-square, Wilcoxon rank sum, and logistic regression.590 patients met inclusion
      criteria (median age 65, 74% African American, 48% female). LVEF was normal in
      79.8%, moderately low in 10.8%, and severely low in 9.3%. A smaller proportion of
      patients with severely low LVEF appeared to have good functional outcome compared
      to other groups (26% vs. 40% vs. 45%, p=0.028); however, this relationship was
      not significant after adjusting for age, baseline National Institute of Health
      Stroke Scale score and admission glucose (OR 0.6, 95% CI 0.3-1.3, p=0.216). Low
      LVEF was not an independent, significant predictor of short-term functional
      outcomes in ischemic stroke patients.

PMID- 24563869
TI  - Exercise induced adipokine changes and the metabolic syndrome.
AB  - The lack of adequate physical activity and obesity created a worldwide pandemic.
      Obesity is characterized by the deposition of adipose tissue in various parts of
      the body; it is now evident that adipose tissue also acts as an endocrine organ
      capable of secreting many cytokines that are though to be involved in the
      pathophysiology of obesity, insulin resistance, and metabolic syndrome.
      Adipokines, or adipose tissue-derived proteins, play a pivotal role in this
      scenario. Increased secretion of proinflammatory adipokines leads to a chronic
      inflammatory state that is accompanied by insulin resistance and glucose
      intolerance. Lifestyle change in terms of increased physical activity and
      exercise is the best nonpharmacological treatment for obesity since these can
      reduce insulin resistance, counteract the inflammatory state, and improve the
      lipid profile. There is growing evidence that exercise exerts its beneficial
      effects partly through alterations in the adipokine profile; that is, exercise
      increases secretion of anti-inflammatory adipokines and reduces proinflammatory
      cytokines. In this paper we briefly describe the pathophysiologic role of four
      important adipokines (adiponectin, leptin, TNF-alpha, and IL-6) in the metabolic
      syndrome and review some of the clinical trials that monitored these adipokines
      as a clinical outcome before and after exercise.

PMID- 24563871
TI  - iNKT cell cytotoxic responses control T-lymphoma growth in vitro and in vivo .
AB  - Invariant natural killer T (iNKT) cells comprise a lineage of CD1d-restricted
      glycolipid-reactive T lymphocytes with important roles in host immunity to
      cancer. iNKT cells indirectly participate in antitumor responses by inducing
      dendritic cell maturation and producing cytokines that promote tumor clearance by
      CD8+ T and NK cells. Although iNKT cells thereby act as potent cellular
      adjuvants, it is less clear whether they directly control the growth of tumors.
      To gain insights into the direct contribution of iNKT cells to tumor immune
      surveillance, we developed in vitro and in vivo systems to selectively examine
      the antitumor activity of iNKT cells in the absence of other cytolytic effectors.
      Using the EL4 T-lymphoma cell line as a model, we found that iNKT cells exert
      robust and specific lysis of tumor cells in vitro in a manner that is
      differentially induced by iNKT cell agonists of varying T-cell receptor (TCR)
      affinities, such as OCH, alpha-galactosyl ceramide, and PBS44. In vitro blockade
      of CD1d-mediated lipid antigen presentation, disruption of TCR signaling, or loss
      of perforin expression significantly reduce iNKT cell killing. Consistent with
      these findings, iNKT cell reconstitution of T, B, and NK cell-deficient mice
      slows EL4 growth in vivo via TCR-CD1d and perforin-dependent mechanisms.
      Together, these observations establish that iNKT cells are sufficient to control
      the growth of T lymphoma in vitro and in vivo. They also suggest that the
      induction of iNKT cell cytotoxic responses in situ might serve as a more
      effective strategy to prevent and/or treat CD1d+ cancers, such as T lymphoma.

PMID- 24563874
TI  - Which is the best strategy for diagnosing bronchial carcinoid tumours? The role
      of dual tracer PET/CT scan.
AB  - Bronchial carcinoids (BC) are rare well-differentiated neuroendocrine tumours
      (NET) sub-classified into typical (TC) and atypical carcinoids (AC). A correct
      pathological identification in the pre-operative setting is a key element for
      planning the best strategy of care, considering the different biological behavior
      of TC and AC. Controversial results have been reported on the diagnostic accuracy
      of fluorine-18-fluorodeoxyglucose positron emission tomography/computed
      tomography ((18)F-FDG PET/CT) in BC. On the other hand, there is increasing
      evidence supporting the use of PET with somatostatin analogues (dotanoc, dotatoc
      or dotatate) labeled with gallium-68 ((68)Ga) in pulmonary NET. Based on
      information obtained by using different radiopharmaceuticals and different (68)Ga
      labeled somatostatin analogues in PET and PET/CT studies, we are able to diagnose
      BC. In conclusion, by using somatostatin receptor imaging and (18)F-FDG PET/CT
      scan, we can differentiate BC from benign pulmonary lesions and TC from AC by
      specific diagnostic patterns. Clinical trials on larger groups of patient would
      allow for a better and "tailored" therapeutic strategy in NET patients using dual
      tracer PET/CT to identify BC and distinguish between TC and AC. 

PMID- 24563875
TI  - Can left ventricular parameters examined by gated myocardial perfusion
      scintigraphy and strain echocardiography be prognostic factors for major adverse
      cardiac events?
AB  - Assessment of left ventricular (LV) function in patients with myocardial
      infarction (MI) provide useful diagnostic and prognostic information. Up to date,
      single photon emission tomography (SPET), positron emission tomography (PET),
      multidetector computed tomographic angiography, echocardiography (EC) and
      magnetic resonance imaging (MRI), have been used to examine LV parameters.
      However, due to limitations of some imaging methods, new studies are directed to
      improve myocardium function evaluation. In conclusion, SEC and GSPET can be
      applied to semi-quantitatively assess LVEF and regional wall motion abnormalities
      in a noninvasive manner. These techniques can provide strong diagnostic and
      prognostic information related to anterior myocardial infarction. In addition to
      this, nitrate enhanced GSPET allows to identify stunning and hibernating
      myocardium. New methods of reconstruction on GSPET systems will better improve
      image quality using lower count rates. 

PMID- 24563876
TI  - Very different external radiation doses in patients undergoing PET/CT or PET/MRI
      scans and factors affecting them.
AB  - Our aim was to determine the external radiation dose rates of patients undergoing
      positron emission tomography/computed tomography (PET/CT) and PET/magnetic
      resonance imaging (MRI) examinations, and to assess the factors affecting these
      doses. The external radiation dose rates (ERDR) from (18)F-FDG were measured
      using the Geiger-Muller tube at a distance of 10, 50, and 100cm from the
      patients' skin surface from various body regions. Results showed that at 10cm
      from the body surface for PET/CT examinations, the ERDR immediately after (18)F
      FDG i.v. injection at time points 1 and 4 was 522.19+/-189.59MUSvh(-1) and
      256.36+/-74.94MUSvh(-1) , respectively. At 10cm from the body surface for PET/MRI
      examinations, the ERDR at time points 1 and 4 were 258.76+/-92.09MUSvh(-1) and
      105.63+/-27.48MUSvh(-1), respectively, always with a precipitous decrease over
      time. The (18)F-FDG dose was on average 1.93-fold higher and the ERDR was higher
      approximately 2.01 to 2.42-fold in PET/CT examinations than in PET/MRI
      examinations. In both PET/CT and PET/MRI patients, the ERDR was significantly
      higher with lower body weight, shorter stature, and fewer urinations etc. In
      conclusion, based on our results, the ERDR to patients from PET/CT scans at a
      distance of 10cm was twice as high than from the PET/MRI. Furthermore, to
      decrease ERDR to the patients, the dose injected should be adjusted to body
      weight and height. Factors like post injection fluid intake and urine bladder
      emptying, decrease ERDR. Other persons should keep a safe distance from the
      injected patient. 

PMID- 24563877
TI  - Sodium selenite enhances thyroid uptake of iodine-131 and regulates thyroid
      function in rats.
AB  - The aim of the present study was to evaluate the role of selenium (Se) on the
      thyroid uptake and retention of radioiodine ((131)I) and on the serum levels of
      thyroid hormones. Experimental rats were divided into four groups with 10 animals
      in each group viz: untreated controls, (131)II-treated, Se-treated and (131)I+Se
      treated. Group II and Group IV animals were injected intraperitoneally with
      3.7MBq of (131)I. Group III and Group IV animals received Se in the form of
      sodium selenite, everyday at a dose of 1ppm in drinking water. Thyroidal (131)II
      uptake measurements, determination of biological half life of (131)I and
      estimation of serum of tri-iodothyronine (T3) and tetra-iodothyronine (T4) and
      thyroid stimulating hormone (TSH) were carried out at two time intervals after 2
      and 4 weeks. The statistical significance of the data was determined by using one
      way analysis of variance (ANOVA) followed by Newman-Keuls test. The results
      showed lower serum levels of T3 and T4 and higher TSH levels in rats treated with
      (131)I when compared to untreated rats. Furthermore, the biological half life
      (Tbiol) of (131)I in thyroid and thyroidal (131)I uptake values at 2h and 24h
      were significantly lower in rats treated with (131)I compared with untrated
      control. Selenium treatment of (131)I treated rats resulted in a significant
      increase in the thyroid uptake as well as Tbiol of (131)I which indicated its
      increased retention. Moreover, normalization of the elevated serum TSH levels and
      a significant increase in the T3 and T4 levels was evident when Se was
      administered to the (131)I treated rats. In conclusion, this study indicates that
      Se when given to rats in the form of sodium selenite, at a dose of 1ppm in
      drinking water enhances the uptake and retention of (131)I in the thyroid as well
      as regulates thyroid hormone levels. 

PMID- 24563878
TI  - Kikuchi-Fujimoto disease as a rare cause of benign lymphadenopathy and (18)F-FDG
      PET/CT findings.
AB  - Kikuchi-Fujimoto disease (KFD) is an uncommon benign and self-limited disease,
      characterized by cervical lymphadenopathy. This disease is generally diagnosed on
      the basis of an excisional biopsy of affected lymph nodes. However, clinical
      presentation and histopathological findings of KFD could lead to a wrong initial
      diagnosis, of tuberculosis, systemic lupus erythymatosus or malignant lymphoma.
      Laboratory tests are not specific. Imaging modalitites give confusing results.
      Affected lymph nodes of patients with KFD can exibit (18)F-FDG uptake on PET/CT
      imaging similar to malignant lymphoma. Therefore, the differential diagnosis of
      KFD should be considered in patients with cervical and/or generalized
      lymphadenopathy. Accurate diagnosis of KFD by histology is essential in avoiding
      unnecessary emotional and mental distress associated with the diagnosis of
      lymphoma. 

PMID- 24563879
TI  - (18)F-FDG-PET/CT, (123)I-MIBG and (99m)Tc-MDP whole-body scans, in detecting
      recurrence of an adult adrenal neuroblastoma.
AB  - Neuroblastoma is the most common extracranial solid malignancy in children, but
      is rare in adults. We report the case of a 33 year old man with recurrence of
      neuroblastoma, 2 years after the excision of the primary tumor in the right
      adrenal gland. The iodine-123-radioiodinated metaiodobenzylguanidine ((123)I
      MIBG) and (99m)Tc-methylene diphosphonate ((99m)Tc-MDP) bone scans and the
      fluorine-18-fluorodeoxyglucose-positron computed tomography ((18)F-FDG PET/CT)
      findings in this patient are presented. First, we applied (123)I-MIBG
      scintigraphy that detected increased uptake at the right adrenal gland region and
      probably at liver lesions and in several bones. Then, the (99m)Tc-MDP bone scan
      revealed also increased uptake of the radiopharmaceutical in bones, but there was
      a discrepancy between these two studies concerning the number and location of the
      lesions. Then, (18)F-FDG PET/CT scan was performed, which showed increased uptake
      of (18)F-FDG at the right adrenal gland region with extension to the liver and
      also in multiple bones. Additionally, an aortocaval lymph node was detected. In
      conclusion, this case indicated that (18)F-FDG PET/CT has defined the extent of
      the recurrence of neuroblastoma in a better way than (123)I-MIBG and (99m)Tc-MDP
      together. 

PMID- 24563880
TI  - The physician who first applied radiotherapy, Victor Despeignes, on 1896.
AB  - Francois-Victor Despeignes, a French physician with significant contribution in
      public hygiene, was the first who had applied the irradiation treatment against
      malignant tumours. During 1866 he had performed to a 52 years old male patient X
      rays treatment for epigastric tumour, paving the way for a new treatment era. 

PMID- 24563881
TI  - Scintigraphic detection of a parotid salivary gland malfunction, in chronic
      sialolithiasis and fat infiltration with no risk factors.
AB  - Long lasting sialolithiasis can cause structural and functional changes of the
      salivary glands, inflammatory infiltration and fibrosis. However fat infiltration
      with sialolithiasis has not been described in the parotid glands. We describe a
      60 years old man, bus-driver who presented with a history of reccurent right
      parotid sialadenitis and was diagnosed to have bilateral sialolithiasis and left
      parotid fat infiltration. Imaging showed large intraparenchymal stones in both
      parotid glands. Gland atrophy with homogeneous fat distribution and severe
      hypofunction were the main imaging findings on the left side. The right parotid
      gland had normal findings in imaging studies. In conclusion, we suggest that
      sialolithiasis caused chronic obstruction, due to increased ductal pressure,
      sialadenitis, fat infiltration, hypofunction and atrophy on the left parotid
      gland. Patient denied further treatment. 

PMID- 24563882
TI  - Bone scintigraphy depicts bilateral atypical femoral stress fractures with
      metachronous presentation, long before a complete fracture occurs.
AB  - Atypical femoral fractures (AFF), although rare, are recognized more often during
      the last decade. They are located in the subtrochanteric region or the femoral
      shaft, may be bilateral, can evolve to complete fractures after bone overload or
      minimal trauma and have specific radiological features. The complete fractures
      have horizontal or slightly oblique configuration accompanied by a medial spike,
      are non-comminuted, and extend to both cortices. There is also generalized
      cortical thickening of femoral shaft. Newer evidence suggests that AFF are stress
      or insufficiency fractures, possibly associated with long-term use of
      bisphoshonates (BP). AFF can also occur in oncologic patients referred for bone
      scintigraphy and, in such a case, they should be differentiated from bone
      metastases. We present here a case with bilateral AFF with metachronous
      appearance in a female patient with a history of breast cancer and osteoporosis.
      The first AFF had been depicted on bone scintigraphy 3 years before a complete
      fracture occurred at this site, but the finding was overlooked. A second bone
      scan performed shortly after the fracture in order to exclude underlying bone
      metastases disclosed an additional unsuspected incomplete AFF in the
      contralateral femur, which was confirmed by radiography. In conclusion,
      oncologists should consider other causes of bone pain besides bone metastatic
      disease, and physicians interpreting whole body bone scans of oncologic patients
      should be aware of the entity of AFF, in order to avoid false positive results
      and provide early information about an impending complete AFF. 

PMID- 24563883
TI  - Hashimoto's autoimmune thyroiditis and vitamin D deficiency. Current aspects.
AB  - Hashimoto's thyroiditis (HT) is a chronic autoimmune thyroid disease caused by an
      interaction between genetic factors and environmental conditions, both of which
      are not yet completely understood. The significant association between vitamin D
      deficiency and HT has been investigated regarding the immune role of this
      hormone. In HT, an immunologic reaction is triggered when thyrocytes express
      major histocompatibility complex (MHC) class II surface HLA-DR antigens, a
      process induced by the production from T helper (Th)1 type lymphocytes, of
      inflammatory cytokines (especially IFN-gamma), which may be inhibited by
      1,25[OH]2D. Genetic polymorphism of vitamin D receptor (VDR), binding protein
      (DBP) and of 1alpha-hydroxylase (CYP1alpha) may also predispose to the
      development of HT. Considering current evidence, presented in this review,
      screening for vitamin D deficiency and careful vitamin D supplementation, when
      required, may be recommended for patients with HT. Further research is needed in
      patients with HT in order to investigate the mechanisms by which vitamin D
      affects autoimmunity and also to evaluate the cost-effectiveness of vitamin D
      supplementation and to suggest the possible optimal dose treatment. 

PMID- 24563884
TI  - Technetium-99m-ubiquicidin scintigraphy in the detection of infective
      endocarditis.
AB  - We present a case of infective endocarditis (IE) diagnosed by the increased
      (99m)Tc-UBI specific uptake in the tricuspid valve region. In conclusion, our
      case data may indicate a first pass-like distribution with strong avidity of the
      tracer to infective endocarditis, facilitating image interpretation. 

PMID- 24563885
TI  - My journey into Aboriginal and Torres Strait Islander health.
AB  - Although all Australian healthcare providers are acutely aware of the health
      outcomes for Aboriginal and Torres Strait Islander peoples, many general
      practitioners may feel unprepared to take on the challenge of working in an
      Aboriginal medical service or in a remote Indigenous community. To highlight the
      immense rewards, without minimising the challenges, AFP invited Dr Lara Wieland,
      a GP with longstanding experience in the front-line of providing primary care for
      Aboriginal peoples, to share her thoughts. 

PMID- 24563886
TI  - General practice encounters with Aboriginal and Torres Strait Islander people.
AB  - In the BEACH program between April 2008 and March 2013, general practitioners
      (GPs) recorded details of 7380 patient encounters with people who identified
      themselves as Aboriginal and Torres Strait Islander, which accounted for 1.5% of
      all BEACH encounters. The rates at which type 2 diabetes and asthma were managed
      at encounters with patients who identified as Aboriginal and Torres Strait
      Islander people were compared with those of other patients. 

PMID- 24563887
TI  - Managing skin infections in Aboriginal and Torres Strait Islander children.
AB  - BACKGROUND: Skin infections are a cause of significant morbidity in Aboriginal
      and Torres Strait Islander populations. OBJECTIVE: This article gives an overview
      of some of the issues to consider when managing a patient with a skin infection.
      These issues may impact on completion of treatment and development of
      complications in the long term. DISCUSSION: Management should consist of
      treatment of the patient through medication and also general measures for the
      patient, their family and the community as a whole. There are significant health
      and socioeconomic burdens placed on communities as a result of the high rate of
      skin disease in some settings.

PMID- 24563888
TI  - Antenatal care for Aboriginal and Torres Strait Islander women.
AB  - BACKGROUND: About 6% of Australian births are to an Aboriginal or Torres Strait
      Islander parent and there is a clear disparity in birth outcomes between
      Aboriginal and Torres Strait Islander and non-Indigenous Australians. Some issues
      affecting birth outcomes are similar nationally whilst others will be more
      particular to certain areas. OBJECTIVE: This paper will highlight important areas
      that may facilitate improved care for Aboriginal and Torres Strait Islander
      women. DISCUSSION: A key component of improving pregnancy outcomes is early and
      ongoing engagement in antenatal care, which is facilitated by the provision of
      culturally appropriate and evidence based care relevant to the local community.
      The majority of Aboriginal and Torres Strait Islander peoples live in urban or
      inner regional areas and receive healthcare through mainstream services and it is
      important therefore for all practitioners to be aware of how to optimise care to
      Aboriginal and Torres Strait Islander women.

PMID- 24563889
TI  - Mental health in Indigenous settings. Challenges for clinicians.
AB  - BACKGROUND: Mental health problems in Aboriginal and Torres Strait Islander
      peoples are common, changing and challenging. Particularly in remote settings,
      doctors will need to untangle the complex interplay of culture, context and
      clinical significance. OBJECTIVE: This paper emphasises the importance of local
      knowledge and cultural respect in complementing clinical competence in the
      management of Aboriginal and Torres Strait Islander peoples with mental health
      problems. DISCUSSION: Anxiety, depression, psychosis, self-harm and problems of
      childhood and old age are used to exemplify differences by comparison with
      practice in non-Indigenous populations.

PMID- 24563890
TI  - Core palliative medicines: meeting the needs of non-complex community patients.
AB  - BACKGROUND: There are a number of challenges facing people in the last days of
      life who wish to receive care in their home environment. This includes timely
      access to medicines for symptom control. OBJECTIVE: This article outlines the
      development of a concise list of core medicines that can provide symptom control
      in non-complex patients in the last days of life. The list is based on practical
      criteria including evidence of efficacy, affordability, the option for parenteral
      administration, availability on the Pharmaceutical Benefits Scheme and the
      doctors' emergency drug supply list. DISCUSSION: A list of core medicines can
      facilitate timely prescribing and supply of essential medicines for end-of-life
      symptom management. However, the development of this list should not replace
      planning and routine involvement of community resources. Multidisciplinary
      education strategies are needed to ensure that the core medicines list is
      utilised effectively by doctors, pharmacists and community nurses.

PMID- 24563891
TI  - Advanced skin squamous cell carcinoma: role of radiotherapy.
AB  - BACKGROUND: We present the case of an elderly man who was referred with a
      neglected, highly advanced skin squamous cell carcinoma on his posterior chest
      wall. The cancer was causing difficult-to-control pain and malodour. OBJECTIVE:
      The treatment and outcomes of local hypofractionated (6 Gray fractions)
      radiotherapeutic management of an advanced lesion are shown. DISCUSSION: The
      treatment could not, for reasons of the radiation tolerance of the lungs, cover
      the entirety of the bulky cancer; ie. the radiotherapy was a balance between not
      exceeding lung tolerance and achieving adequate tumour coverage. Keeping the
      treatment simple was also important, as the aim of therapy was palliation, and
      the patient's ability to lie reproducibly still was compromised. Hence, he was
      treated with large, weekly fractions - such treatment is useful in the palliative
      setting, as it minimises patient discomfort and inconvenience. The treatment
      achieved significant tumour regression, complete relief of pain, arm lymphoedema
      and a large reduction in malodour.

PMID- 24563892
TI  - An itchy rash on the fingertips - a case study.
AB  - A case study A previously healthy woman, aged 37 years, presented with a 4-week
      history of pruritic periungual rash and subungual pain. Physical examination
      revealed scaly, fissured, erythematous plaques around her fingernails (Figure 1).
      Underneath the acrylic artificial nails that she had been wearing for 6 weeks,
      onycholysis and nail bed hyperkeratosis were evident. Oral terbinafine and
      amorolfine nail polish were prescribed by the general practitioner but had no
      clinical benefit. 

PMID- 24563894
TI  - Approach to low back pain. Chiropractic.
AB  - Case study. A man aged 42 years, who works as a police officer, presented with
      severe lower back pain, which he had experienced for 24 hours after spending the
      previous day helping his brother to move house. He had difficulty ambulating and
      most movements aggravated the pain. There were no lower limb symptoms and no red
      flags present on history or examination. He was otherwise well and was not taking
      any regular medications.

PMID- 24563893
TI  - Klinefelter syndrome - a general practice perspective.
AB  - BACKGROUND: Klinefelter syndrome (KS) is a common genetic condition affecting one
      in 450 men, but is only diagnosed in fewer than half of those affected.
      OBJECTIVE: To increase awareness among general practitioners of their role in the
      diagnosis and management of KS. DISCUSSION: KS has a highly varied phenotype
      comprising a range of physical and psychosocial features and comorbidities. For
      patients diagnosed with KS, a range of management strategies can be used to
      improve health outcomes and quality of life.

PMID- 24563895
TI  - Management of smoking in pregnant women.
AB  - BACKGROUND: Smoking is the most important preventable cause of adverse outcomes
      in pregnancy. However, most smokers who become pregnant continue to smoke and
      most of those who quit relapse after delivery. OBJECTIVE: This article explores
      the relationship between smoking and pregnancy, and reviews the evidence for best
      practice intervention by general practitioners. DISCUSSION: Continuing to smoke
      during pregnancy is strongly associated with socioeconomic disadvantage, mental
      illness and Aboriginal and Torres Strait Islander populations. Quitting is more
      difficult for these groups and interventions assist only sixin every 100 pregnant
      smokers to quit. Behavioural counselling is the first-line treatment. Nicotine
      replacement therapy (NRT) can be offered if the smoker is unable to quit without
      it, although its efficacy is uncertain. Adequate doses of nicotine and good
      adherance may be required for the best results. The use of NRT in pregnancy is
      likely to be less harmful than continuing to smoke. Women should be encouraged to
      quit smoking before becoming pregnant.

PMID- 24563896
TI  - Factors affecting medical students' sense of belonging in a longitudinal
      integrated clerkship.
AB  - BACKGROUND: Longitudinal integrated clerkships (LICs) have been shown to be
      effective educationally and may assist in promoting rural career choices when
      undertaken in rural communities. Despite these merits, some students find LICs
      challenging. METHODS: Students from a regional medical school undertaking a LIC
      participated in semi-structured interviews. A template approach was used for
      analysis of the transcripts. RESULTS: Thirteen students participated. Three major
      themes were identified: academic leadership, external (general practice)
      environment and intrinsic (student) factors. Optimally, a synergistic
      relationship between factors, facilitated by academic leadership, resulted in a
      sense of belonging. DISCUSSION: Our findings support the concept that there is a
      highly dynamic interaction between factors determining the experience of students
      in the LIC. The individual nature of learners and the learning contexts require
      multi-level academic leadership.

PMID- 24563897
TI  - What do GPs need to work more effectively with Aboriginal patients? Views of
      Aboriginal cultural mentors and health workers.
AB  - BACKGROUND: Given the health inequity faced by Aboriginal people, it is important
      that interactions with general practitioners (GPs) are effective and that GPs are
      aware of issues affecting culturally competent practice. METHODS: Semi-structured
      interviews undertaken with Aboriginal people who had a role in cultural support
      or mentorship of GPs and registrars in urban or large rural centres were analysed
      thematically. RESULTS: Fourteen participants contributed to the study. They
      emphasised that a culturally respectful approach was the most important
      attribute. Other core knowledge and skills that promote effective relationships
      and healthcare were categorised as attitudes and approach, communication and
      consultation skills, culturally aware practices and applied knowledge.
      DISCUSSION: Respectful attitudes and good communication and consultation skills
      need to be combined with knowledge of the historical, cultural, social, medical
      and system factors that impact on healthcare delivery for Aboriginal patients.
      Access to cultural mentorship or support is important to promote culturally
      competent practice.

PMID- 24563898
TI  - General practice registrar perceptions on training medical students.
AB  - BACKGROUND: Around Australia general practice teaching capacity is stretched as
      there are more learners at all levels. Vertical integration has been identified
      as a part of the solution. This system relies on involvement of registrars.
      METHODS: This study involved semi-structured interviews with registrars and
      supervisors in the Northern Territory to determine their perceptions of
      supervising students in general practice. RESULTS: Registrars described
      themselves as more thorough when they had a student, altering their consultations
      to set a good example and ensure professional credibility. They saw advantages
      for their patients and for their learning. Thoroughness slowed them down and was
      the main barrier for teaching, particularly if it resulted in seeing fewer
      patients and reducing their income. Lack of physical space constrained teaching
      opportunities. DISCUSSION: Registrars are willing to be part of the medical
      education workforce in the NT. They require training in how to supervise
      students, and confidence in consulting skills. With increased access to
      consulting rooms, registrars can allow students to commence seeing patients
      before joining the consultation, improving learning opportunities and patient
      flow. Alternative models of employment could overcome time and financial
      constraints.

PMID- 24563900
TI  - Generalism workforce planning. Definitional, pragmatic and transformational
      issues.
AB  - BACKGROUND: Generalist primary care medical practitioners have been the
      cornerstone of healthcare systems through general practice. Internationally and
      within Australia, calls to strengthen generalist primary care medical practice
      have increased with the ever growing burden on the health system from the demand
      and workforce sides. Professional bodies have called for further work to quantify
      and predict generalist workforce requirements and distribution as a matter of
      urgency. Despite recent Australian health workforce planning analysis and
      modelling predicting workforce number requirements, definitional, pragmatic and
      transformational issues confront generalism workforce planning. OBJECTIVE: This
      article describes the challenges involved in generalist workforce planning and
      suggests potential solutions. DISCUSSION: We argue for a generalist workforce
      capability-based model that seeks to identify how to prepare, support and sustain
      core capabilities required for generalists to ensure team-based primary care is
      safe and effective within and across sectors and settings.

PMID- 24563901
TI  - A is for aphorism. 'A normal person is only someone who hasn't been investigated
      enough yet'.
AB  - Every year I read many applications for research grants, mostly for the National
      Health and Medical Research Council (NHMRC). Most start in roughly the same way:
      an estimate of the number of people suffering from the disease in question and
      the cost of the disease to the economy. From reading these applications, one
      would think the health of Australians is in crisis and the economic effects of
      ill health devastating. The evidence, however, is quite the reverse. Australians
      currently enjoy one of the longest life expectancies in human history. Adult male
      mortality rates have fallen from 207 per 1000 male adults in 1970 to 81 in 2009;
      female mortality rates have fallen from 117 to 47 in the same period. These
      trends continue to improve. There has been a spectacular decline in the
      prevalence of cardiovascular disease in Australia from the levels seen in the
      1960s and 1970s. In the 2011-2013 Australian health survey, over half of the
      population rated their health as very good or excellent; there had been no change
      from 5 years previously, despite the ageing of the population. Even in the age
      group of 85 years and over, 60% rate their health as good to excellent. 

PMID- 24563902
TI  - In the wake of Angelina - managing a family history of breast cancer.
AB  - BACKGROUND: Accurate risk assessment by general practitioners (GPs) of breast and
      ovarian cancer for unaffected women with a family history is important to ensure
      appropriate referral. Family cancer clinics can provide significant benefits for
      those at high risk, but genetic testing is unlikely to benefit those who are
      unaffected, or have little or no family history. The overwhelming increase in
      referrals following celebrity Angelina Jolie's decision to have a risk-reducing
      mastectomy because she carries a gene mutation has put pressure on services.
      OBJECTIVE: To provide information for GPs about managing women with concerns
      about their family history of breast cancer and highlight the resources
      available. DISCUSSION: GPs are well placed to assess risk of breast and ovarian
      cancer and are encouraged to use the available resources to assist them in
      appropriate risk assessment and referral.

PMID- 24563903
TI  - Rapid, in situ detection of cocaine residues based on paper spray ionization
      coupled with ion mobility spectrometry.
AB  - In this paper, a novel approach based on paper spray ionization coupled with ion
      mobility spectrometry (PSI-IMS) was developed for rapid, in situ detection of
      cocaine residues in liquid samples and on various surfaces (e.g. glass, marble,
      skin, wood, fingernails), without tedious sample pretreatment. The obvious
      advantages of PSI are its low cost, easy operation and simple configuration
      without using nebulizing gas or discharge gas. Compared with mass spectrometry,
      ion mobility spectrometry (IMS) takes advantage of its low cost, easy operation,
      and simple configuration without requiring a vacuum system. Therefore, IMS is a
      more congruous detection method for PSI in the case of rapid, in situ analysis.
      For the analysis of cocaine residues in liquid samples, dynamic responses from 5
      MUg mL(-1) to 200 MUg mL(-1) with a linear coefficient (R(2)) of 0.992 were
      obtained. In this case, the limit of detection (LOD) was calculated to be 2 MUg
      mL(-1) as signal to noise (S/N) was 3 with a relative standard deviation (RSD) of
      6.5% for 11 measurements (n = 11). Cocaine residues on various surfaces such as
      metal, glass, marble, wood, skin, and fingernails were also directly analyzed
      before wiping the surfaces with a piece of paper. The LOD was calculated to be as
      low as 5 ng (S/N = 3, RSD = 6.3%, n = 11). This demonstrates the capability of
      the PSI-IMS method for direct detection of cocaine residues at scenes of cocaine
      administration. Our results show that PSI-IMS is a simple, sensitive, rapid and
      economical method for in situ detection of this illicit drug, which could help
      governments to combat drug abuse. 

PMID- 24563904
TI  - Analytical approaches for quantification of a Nrf2 pathway activator: overcoming
      bioanalytical challenges to support a toxicity study.
AB  - Activation of the Nrf2 stress pathway is known to play an important role in the
      defense mechanism against electrophilic and oxidative damage to biological
      macromolecules (DNA, lipids, and proteins). Chemical inducers of Nrf2 such as
      sulforaphane, dimethyl fumarate (Tecfidera(r)), CDDO-Me (bardoxolone-methyl), and
      3-(dimethylamino)-4-((3-isothiocyanatopropyl)(methyl)amino)cyclobut-3-ene-1,2
      dione (a synthetic sulforaphane analogue; will be referred to as ) have the
      ability to react with Keap1 cysteine residues, leading to activation of the
      Antioxidant Response Element (ARE). Due to their electrophilic nature and poor
      matrix stability, these compounds represent great challenges when developing
      bioanalytical methods to evaluate in vivo exposure. like SFN reacts rapidly with
      glutathione (GSH) and nucleophilic groups in proteins to form covalent adducts.
      In this work, three procedures were developed to estimate the exposure of in a
      non-GLP 7 day safety study in rats: (1) protein precipitation of blood samples
      with methanol containing the free thiol trapping reagent 4-fluoro-7
      aminosulfonylbenzofurazan (ABD-F) to measure GSH- and N-acetylcysteine conjugated
      metabolites of ; (2) an Edman degradation procedure to cleave and analyze N
      terminal adducts of at the valine moiety; and (3) treatment with ammonium
      hydroxide to measure circulating free- and all sulfhydryl bound . 

PMID- 24563905
TI  - Symmetric cyanovinyl-pyridinium triphenylamine: a novel fluorescent switch-on
      probe for an antiparallel G-quadruplex.
AB  - In this study, we present a fluorescent switch-on probe based on a cyanovinyl
      pyridinium triphenylamine (CPT) derivative that exhibited a 190-fold increase in
      fluorescence upon binding to G-quadruplex-forming oligonucleotide 22AG. This
      probe showed specificity and selectivity towards an antiparallel G-quadruplex,
      indicating its promising potential in G-quadruplex imaging. 

PMID- 24563906
TI  - Spatially marking and quantitatively counting membrane immunoglobulin M in live
      cells via Ag cluster-aptamer probes.
AB  - A probe composed of an aptamer and a silver cluster, where the aptamer targets
      mIgM of live cells and the silver cluster provides fluorescent imaging and mass
      quantification of mIgM of live cells, is presented. This new probe simultaneously
      provides accurate spatial and mass information of mIgM in live cells. 

PMID- 24563907
TI  - Trend and socio-demographic differentials of Caesarean section rate in Addis
      Ababa, Ethiopia: analysis based on Ethiopia demographic and health surveys data.
AB  - BACKGROUND: According to the World Health Organization, Caesarean Section (CS)
      rate (percentage of births managed by CS) exceeding 15% lacks medical
      justification and it could be linked with adverse maternal and child health
      consequences. Nonetheless, the rate in Addis Ababa city is beyond the
      aforementioned level. The objectives of the study were to assess the trend and
      socio-demographic differentials of CS rate in the city. METHODS: The study was
      made based on the three Ethiopia Demographic and Health Surveys (EDHS) data (EDHS
      2000, 2005 and 2011). The trend over the period of 1995-2010 was assessed using
      simple linear regression analysis whereas the differentials of CS rate were
      identified based on DHS 2011 data. CS rates were compared across categories of
      various socio-economic variables using chi-square test. RESULTS: The CS rate
      increased significantly from 2.3% in 1995-1996 to 24.4% in 2009-2010. From 2003
      onwards, it persisted above 15%. The rates among women with secondary (32.3%) or
      higher (33.3%) levels of education were nearly two times higher than the
      corresponding figures in the illiterates (14.8%) and women with primary education
      (15.8%) (P < 0.001). The level among women from the 'rich' households (28.6%) was
      higher than those from the 'poor' (16.4%) and 'middle' (19.5%) households (P =
      0.016). The rate also significantly increased with rising parity (P = 0.023). The
      rate among women who delivered in private health institutions (41.7%) was twice
      higher than their counterparts who delivered in public institutions (20.6%).
      CONCLUSION: The CS rate in Addis Ababa has exceeded beyond the level recommended
      by the WHO. Accordingly, It should be maintained within the optimum 5-15% range
      by introducing medical audit for labor management both in the private and public
      health institutions.

PMID- 24563909
TI  - Response.  Intrauterine growth references are appropriate to  monitor postnatal
      growth of preterm neonates.
AB  - No growth chart has resolved what to do with the physiologic postnatal weight
      loss when extracellular water is decreased. Nevertheless, the Fenton Growth Chart
      provides the most comprehensive comparison to the current growth standard for the
      preterm infant particularly with growth after return to birthweight. Existing
      postnatal growth references have limitations since they are based on less than
      ideal samples, and do not provide guidance about the importance of any deviations
      from the mean of the reference samples. Errors in length measurement have been
      found to be evenly distributed as under and overestimations, and therefore are
      unlikely to introduce bias.

PMID- 24563910
TI  - Topics of a wide range: from cancer to ulcer pain and facial wrinkles, and from
      chlamydia tests to herbal drug allergy.

PMID- 24563911
TI  - Response to "change in dermoscopic pattern of naevi in children" by Scope et al.

PMID- 24563912
TI  - A broad-spectrum approach to daily tadalafil: making the big picture even bigger.

PMID- 24563913
TI  - Fears for the woods and the trees.

PMID- 24563914
TI  - Q & A: Zhenbiao Yang.

PMID- 24563915
TI  - Regulation of toxin production in the pathogenic clostridia.
AB  - The genus Clostridium comprises a large, heterogeneous group of obligate
      anaerobic, Gram-positive spore forming bacilli. Members of this genus are
      ubiquitous in the environment and although most species are considered
      saprophytic, several are pathogenic to both humans and animals. These bacteria
      cause a variety of diseases including neuroparalysis, gas gangrene, necrotic
      enteritis, food poisoning, toxic shock syndrome and pseudomembraneous colitis,
      which in most cases arise as a consequence of the production of potent exotoxins.
      Treatment options are often limited, underscoring the need for new treatment
      strategies and novel therapeutics. Understanding the fundamental mechanisms and
      signals that control toxin production in the pathogenic clostridia may lead to
      the identification of novel therapeutic targets that can be exploited in the
      development of new antimicrobial agents.

PMID- 24563916
TI  - Economic burden of routine hematologic tests and intensive care unit observation
      for elective anterior cervical discectomy and fusion.
AB  - BACKGROUND: Anterior cervical discectomy and fusion is one of the most common
      surgical interventions performed by spine surgeons. As efforts are made to
      control healthcare spending because of the limited or capped resources offered by
      the National Health Insurance, surgeons are faced with the challenge of offering
      high-level patient care while minimizing associated healthcare expenditures.
      Routine ordering of postoperative hematologic tests and observational intensive
      care unit (ICU) stay might be areas of potential cost containment. This study was
      designed to determine the necessity of routine postoperative hematologic tests
      and ICU stay for patients undergoing elective anterior cervical discectomy and
      fusion and to investigate whether the elimination of unnecessary postoperative
      laboratory blood studies and ICU stay inhibits patient care. METHODS: The
      necessity for postoperative blood tests was determined if there were needs for a
      postoperative blood transfusion and hospital readmission within 1 month after
      surgery. The necessity for postoperative ICU observation was decided if immediate
      surgical intervention was required when any kind of complications occurred during
      the ICU stay. RESULTS: There were 168 patients collected in the study. Among
      them, all had routine preoperative and postoperative blood tests and were
      transferred to ICU for observation. No need for blood transfusion was observed,
      and no patient required immediate surgical intervention when the complications
      occurred during the ICU stay. CONCLUSION: Cost savings per admission amounted to
      approximately 10% of the hospitalization cost by the elimination of unnecessary
      postoperative routine laboratory blood studies and observational ICU stay without
      waiving patient care in the current volatile, cost-conscious healthcare
      environment in Taiwan.

PMID- 24563917
TI  - Placement of a new tunneled hemodialysis catheter through the old exit site with
      simultaneous disruption of a fibroepithelial sheath.

PMID- 24563918
TI  - No adverse impact of depressive symptoms on the effectiveness of postacute care
      service: a multicenter male-predominant prospective cohort study.
AB  - BACKGROUND: Although the clinical effectiveness of community hospital-based
      postacute care (PAC) services has been shown, little was known regarding the
      impact of depression on the clinical outcomes of older patients receiving PAC
      services in Taiwan. METHODS: From January 2009 to August 2010, patients aged 65
      years and older referred from tertiary medical centers or acute wards of
      community hospitals to PAC units were invited for study. All patients received
      the 4-week Comprehensive Geriatric Assessment-based intervention program in the
      PAC units. The functional assessment was composed of Geriatric Depression Scale
      Short Form (GDS), Mini-Mental Status Examination, Barthel Index, Instrumental
      Activities of Daily Living, and Braden Score. RESULTS: Among the 401 participants
      (mean age, 82.0 years; 95.5% males), 66 (16.5%) patients were depressed at PAC
      unit admission. Depressed patients had significantly lower Barthel Index (38.1 +/
      2.4 vs. 47.6 +/- 1.2, p = 0.002) and Braden Score (17.7 +/- 0.3 vs. 18.8 +/-
      0.2, p = 0.004) than nondepressed patients. Improvement was noted on all measures
      of functional outcome among patients receiving PAC services. Furthermore, GDS was
      significantly improved in depressed patients (from 6.4 +/- 0.2 to 2.8 +/- 0.2 in
      depressed patients vs. from 1.6 +/- 0.1 to 0.9 +/- 0.1 in nondepressed patients,
      p < 0.001). CONCLUSION: Depression was common when patients were newly admitted
      to PAC services, which was highly associated with poorer physical function.
      Improvement in physical function and depressive symptoms among all patients after
      PAC service was found, and the presence of depressive symptoms at PAC admission
      did not predict any adverse outcome of PAC services.

PMID- 24563919
TI  - Sensitivity to change of oral and general health-related quality of life during
      prosthodontic treatment.
AB  - The literature presents conflicting findings on whether health-related quality of
      life (HRQoL) measures have sufficient evaluative properties to assess changes
      caused by dental interventions. The aim of our study was to compare sensitivity
      to change in HRQoL and OHRQoL in prosthodontic patients. In this prospective
      intervention study, a total of 165 consecutively recruited patients completed the
      Short Form-36 (SF-36) and the 49-item Oral Health Impact Profile (OHIP), as self
      administered questionnaires, before prosthodontic treatment and 1 month after
      treatment was finished. Differences in SF-36 and OHIP scores between baseline and
      follow up were tested for statistical significance using paired t-tests. Effect
      sizes (Cohen's d) were calculated. Health-related quality of life improved during
      prosthodontic treatment, indicated by a slight, but statistically significant,
      increase in the SF-36 physical component (difference: 1.0 points), whereas
      perceived mental health did not change substantially (difference: -0.5 points).
      Improvement in OHRQoL (difference in OHIP sum score: -6.7 points) was
      statistically significant. Although the OHIP effect size (of 0.2) was considered
      as small, according to guidelines, it was greater than for the SF-36 component
      scores (physical: 0.1; mental: 0.1). Sensitivity to change in quality of life
      measures was greater for OHRQoL than for HRQoL, limiting the usefulness of HRQoL
      as an outcome measure in dentistry.

PMID- 24563920
TI  - Progress, public health and vested interests.

PMID- 24563921
TI  - Post-operative hyponatraemic encephalopathy: a successful outcome despite
      hypoxia.
AB  - Hyponatraemia is the most common electrolyte disorder encountered in clinical
      practice. Symptomatic hyponatraemia reflects brain damage because of cerebral
      swelling. Some coexisting factors such as extreme ages, hypoxia and female sex
      are associated with poor prognosis. In this report, we describe the case of a 75
      year-old patient who suffered from hyponatraemic encephalopathy after elective
      vaginal hysterectomy under spinal anaesthesia. After being transferred to the
      ward, she developed nausea, vomiting, hypertensive crisis and intense anxiety.
      These symptoms were followed by grand mal seizure. Serum sodium level was 108
      mmol/l. She also presented hypoxia, considered an aggravating factor, which was
      probably caused by the combination of benzodiazepine intake and cerebral oedema.
      However, fast raise of serum sodium level was achieved by immediate treatment
      with hypertonic saline, and she was discharged home without any sequelae.

PMID- 24563922
TI  - Intrathecal chloroprocaine vs. lidocaine in day-case surgery: recovery, discharge
      and effect of pre-hydration on micturition.
AB  - BACKGROUND: This randomised, double blind prospective study compares intrathecal
      lidocaine with chloroprocaine in day-case surgery and the influence of a 500 ml
      pre-load intravenously. We tested the hypothesis that chloroprocaine provides
      faster recovery and discharge in day-case surgery. Secondary we studied the
      influence of a preload compared with fluid restriction on discharge time and
      micturition problems. METHODS: One hundred patients undergoing day-case
      arthroscopy were randomised to receive either lidocaine (L) 60 mg or
      chloroprocaine (CP) 40 mg intrathecally and this with (L+, CP+) or without (L-,
      CP-) a 500 ml pre-load of crystalloid. Block characteristics, micturition and
      discharge times were registered. Bladder volumes were monitored by ultrasound.
      Micturition problems received a micturition score. RESULTS: Onset and quality of
      the block were comparable between groups. Time to regain Bromage 1 and L2
      regression were shorter for the CP group compared with the L group. Voiding (168
      +/- 44 min) and discharge (178 +/- 52 min) were approximately 40 min faster for
      the CP group compared with the L group. Pre-load provided faster bladder filling
      but there were no differences in voiding time within the CP or L group. The CP+
      group (166 +/- 36 min) was discharged faster than both L groups (226 +/- 57 min,
      227 +/- 59 min). More serious micturition problems occurred in the L+ group
      compared with both CP groups. CONCLUSION: Chloroprocaine is suitable for day-case
      surgery because of faster block regression and discharge than lidocaine. A 500 ml
      pre-load may not affect discharge but did not increase micturition problems for
      chloroprocaine.

PMID- 24563923
TI  - Over-reliance on assays for specific IgE in diagnostics of penicillin allergy?-
      Reply.

PMID- 24563924
TI  - Basophil activation test (BAT) in the diagnosis of immediate hypersensitivity
      reactions to radiocontrast media--reply.

PMID- 24563927
TI  - Commentary on the inclusion of persistent complex bereavement-related disorder in
      DSM-5.
AB  - The DSM-5 Anxiety, Obsessive-Compulsive Spectrum, Posttraumatic, and Dissociative
      Disorders Work Group has proposed criteria for Persistent Complex Bereavement
      Related Disorder (PCBRD) for inclusion in the appendix of DSM-5. The authors feel
      that it is important that dysfunctional grief will become a formal condition in
      DSM-5 because that would facilitate research and would imply recognition of the
      suffering of a significant minority of bereaved individuals who experience
      difficulties in their process of recovery from loss. However, as detailed in this
      commentary, we oppose the inclusion of the proposed criteria set for PCBRD for
      several reasons, including the fact that these criteria lack empirical evidence.
      In our view, it is better to include empirically validated criteria for prolonged
      grief disorder in DSM-5, possibly expanded with a few symptom criteria that are
      tapped by the Inventory of Complicated Grief the most widely used instrument to
      measure dysfunctional grief.

PMID- 24563926
TI  - Re: the MiniArc sling for female stress urinary incontinence: clinical results
      after 1-year follow-up.

PMID- 24563925
TI  - Autologous stem cell transplantation in mantle cell lymphoma: a report from the
      SFGM-TC.
AB  - Autologous stem cell transplantation (ASCT) is considered as an attractive
      treatment option for young mantle cell lymphoma (MCL) patients. This
      retrospective SFGM-TC study analyzed the outcome of 500 MCL patients treated with
      ASCT and investigated parameters that may modify the outcome of patients who
      proceeded to ASCT upfront (n=396). For all patients, median age at ASCT was 56
      years (range, 26-71). Median follow-up was 34 months. Three-year progression free
      survival (PFS) and overall survival (OS)were 63.5% [95 % CI, 58.7-68.6 %] and
      79.5 % [95 % CI, 75.3-83.4 %], respectively. Median time from ASCT to relapse was
      22 months (range, 0-136 m). For patients transplanted upfront and in multivariate
      analysis, age (HR=2 [1.2-3.4], p=.01, and HR=2.3 [1.2-4.5], p=.01), disease
      status at time of ASCT (HR=1.7 [1.1-2.6], p=.01 and HR=1.8 [1.1-3.1], p=.03), and
      use of rituximab (HR=0.5 [0.3-0.8], p=.002 and HR=0.5 [0.3-0.9], p=.01) were
      statistically predictive for both PFS and OS. Also, first line treatment
      including anthracycline and high-dose cytarabine followed by ASCT conditioned
      with TAM improved PFS. To conclude, this study suggests that ASCT in MCL can
      provide a high response rate but may not be sufficient to cure MCL even when ASCT
      is performed upfront, highlighting the need for innovative approaches before
      ASCT, aiming to increase complete response rate, and after ASCT, to maintain
      response.

PMID- 24563928
TI  - Innovative moments in grief therapy: reconstructing meaning following perinatal
      death.
AB  - This article presents an intensive analysis of a good outcome case of
      constructivist grief therapy with a bereaved mother, using the Innovative Moments
      Coding System (IMCS). Inspired by M. White and D. Epston's narrative therapy, the
      IMCS conceptualizes therapeutic change as resulting from the elaboration and
      expansion of unique outcomes (or as we prefer, innovative moments), referring to
      experiences not predicted by the problematic or dominant self-narrative. The IMCS
      identifies and tracks the occurrence of 5 different types of innovative moments:
      action, reflection, protest, re-conceptualization, and performing change. Results
      documented the process of meaning reconstruction over the 6 sessions of
      treatment, and demonstrated the feasibility and reliability of analyzing
      narrative change in this form of grief therapy, opening it to comparison with
      other approaches.

PMID- 24563929
TI  - The effect of mortality salience on implicit bias.
AB  - Previous research in terror management theory has shown that when individuals are
      reminded of their mortality, negative evaluations of out-group members increase.
      This previous research has used a variety of methods to investigate the change in
      attitudes toward out-group members. These methods generally permit participants
      time to consciously reflect during responding In the present study, the authors
      hypothesized that reminding individuals of their mortality would increase
      implicit bias toward out-group members when measured with the Implicit
      Association Test (IAT). In the experiment, White participants were randomly
      assigned to complete a written essay about imagining their own death (i.e.,
      mortality salience condition) or an essay regarding an upcoming exam (i.e.,
      control condition), and then participants completed an evaluative IAT. The
      results revealed that participants who had been reminded of their mortality took
      longer to associate names of Black individuals with positive words when compared
      to a control group. The implications of these findings are considered.

PMID- 24563930
TI  - Experiences of causing an accidental death: an interpretative phenomenological
      analysis.
AB  - Accidentally killing or feeling responsible for another person's death
      constitutes an event that is different from many typical traumatic stressors in
      that the responsibility for causing the trauma is located in the person
      themselves, rather than another person or persons. Research exploring the
      perspective of those who have accidentally caused a death is extremely sparse.
      This study aimed to gain an insight into the lived experiences of people who have
      caused an accidental death. Five participants were recruited through an on-line
      advertisement; all were drivers directly involved in a road traffic accident that
      occurred unexpectedly, without intention and resulted in a person's death. An
      interpretive phenomenological approach was used to analyse data collected through
      semi-structured interviews. Three main themes emerged from the participants'
      accounts: trying to make sense of a life changing moment; struggling to cope with
      the trauma of causing a death, and a changed sense of self. These findings
      highlight the considerable and enduring trauma associated with causing an
      accidental death, and emphasise the need to develop appropriate interventions to
      help alleviate this psychological distress.

PMID- 24563931
TI  - Psychometric characteristics of the Duke Social Support Index in a young rural
      Chinese population.
AB  - The study is aimed to examine the psychometric characteristics of the Duke Social
      Support Scale (DSSI) in young rural Chinese individuals (379 suicides, 411
      controls) aged 15-34 years. Social support was measured by 23-item DSSI, which
      included Social Interaction Scale, Subjective Social Support, and Instrumental
      Social Support. DSSI had high internal consistency (alphas all over .79) and
      correlated with hopelessness and anxiety in both samples. Confirmatory factor
      analysis showed that the structure models of DSSI were basically suitable for the
      original structure of DSSI but some items should be modified or deleted.
      Altogether, these findings support that DSSI has high reliability and validity,
      which makes it an acceptable measure for social support in young Chinese
      populations. However, further model tests should be carried out by deleting or
      modifying some items or being used in different populations.

PMID- 24563932
TI  - Five residents speak: the meaning of living with dying in a long-term care home.
AB  - Personal meanings given to the experience of living with nursing home death were
      shared by 5 nursing home residents. Data were collected using semi-structured
      interviews. Using M. van Manen's (1990) hermeneutic phenomenology, the lived
      experience of residents emerged as a compilation of 5 dynamically occurring
      themes, including (a) mapping relations, (b) pacing oneself (c) maintaining
      belongingness, (d) reconciling death as part of life, and (e) engaging in
      preparatory review. The overarching essence of the lived experienced was defined
      as reflection toward resolution of dying as a "resident" in a sea of life gains
      and losses. Residents' expressions revealed that living with peers' dying in a
      nursing home is closely entwined with how life is experienced during one's final
      days.

PMID- 24563933
TI  - Finding meaning in loss: the mediating role of social support between personality
      and two construals of meaning.
AB  - Dimensions of personality may shape an individual's response to loss both
      directly and indirectly through its effects on other variables such as an
      individual's ability to seek social support. The mediating effect of social
      support on the relationship between personality (i.e., extraversion and
      neuroticism) and 2 construals of meaning (i.e., sense-making and benefit-finding)
      among 325 bereaved individuals was explored using path analysis. Supporting our
      hypotheses, social support mediated the relationship between personality and
      construals of meaning. Neuroticism was negatively and indirectly associated with
      both sense-making and benefit-finding through social support. Extraversion had a
      significant positive relationship to social support, which, in turn, mediated the
      impact of extraversion on both sense-making and benefit finding. The model
      explained 35% of the variance in social support, 19% of the variance in sense
      making, and 25% of the variance in benefit-finding. Implications are discussed in
      light of existing theories of bereavement and loss.

PMID- 24563934
TI  - Helpful aspects of bereavement support for adults following an expected death:
      volunteers' and bereaved people's perspectives.
AB  - Helpful and unhelpful aspects of bereavement support were investigated from the
      perspectives of 24 bereaved adults and their volunteer bereavement support
      workers. Most commonly reported themes were the provision of hope and
      reassurance, and the opportunity for continued sharing and support. Significantly
      more clients than volunteers reported provision of information, and talking to
      someone outside their social network as helpful, and both groups scored higher on
      helpfulness ratings than comparative groups of psychotherapists and clients.
      Clients' grieving styles and the quality of the helping relationship were also
      related to what was seen as helpful.

PMID- 24563935
TI  - Suicide bulletin board systems comparison between Japan and Germany.
AB  - An online questionnaire (n = 301) was conducted to analyze the cross-cultural
      influence of the use of suicide bulletin board systems. Factor analysis
      demonstrated that participants had two types of motives: the constructive motive
      of mutual help and the destructive motive of suicide preparation. The results
      showed that suicidal thoughts did not worsen with suicide bulletin board systems
      usage, and there is no difference in the demographic data, motives of the
      participants, and the effects of the suicide message boards between Japan and
      Germany.

PMID- 24563936
TI  - Grief as a social emotion: theoretical perspectives.
AB  - The article explores a sociological perspective on grief as a social emotion.
      Focusing on the social bond with the deceased, the self-concept of the survivor
      or the power of feeling rules, general sociological theories of emotions
      (symbolic interactionism, structural theory, behavioral theory) have the
      potential to deepen the understanding of grief as a social emotion. The article
      concludes by presenting a cognitive-structural model of grief that integrates the
      different theoretical elements.

PMID- 24563937
TI  - Validation of reasons for living and their relationship with suicidal ideation in
      Korean college students.
AB  - This study aimed to examine the validity of reasons for living (RFL) and the
      protective role they may play against suicidal ideation in college students in
      South Korea. A total of 277 undergraduate students participated by completing the
      College Student Reasons for Living Inventory (CS-RFL), along with measures of
      suicide risk including depression, hopelessness, and suicidal ideation. The five
      CS-RFL subscales displayed strong negative correlations with the three indicators
      of suicide risk. Hierarchical regression analysis results revealed significant
      main effects of Survival and Coping Beliefs and Moral Objections to Suicide on
      suicidal ideation after controlling for depression and hopelessness. Moreover, a
      general tendency toward lower levels of RFL, especially Moral Objections and
      Responsibility to Family and Friends, was observed compared to those reported in
      Asian American and European American students. Qualitative studies are needed to
      increase the validity of RFL inventories and verify whether the observed cultural
      differences, such as lower Moral Objections, are due to actual variance in
      underlying belief systems or mere systematic effects of the study variables or
      measurement bias. Overall, the strong relationship between RFL and suicidal
      ideation suggest that RFL may be an important factor in assessing suicide risk
      and devising preventive measures for Korean college students.

PMID- 24563938
TI  - Dreams of deceased children and countertransference in the group psychotherapy of
      bereaved mothers: clinical illustration.
AB  - This article presents, in the form of a clinical illustration, a therapeutic
      group of bereaved mothers with special reference to their dreams about their
      deceased children. The article presents descriptions of the emotions of these
      mothers and countertransference feelings, a topic that, to our knowledge, has not
      been frequently studied. The group was small, analytically oriented, slow-open,
      comprised of women bereaved by the death of a child, and conducted by a female
      therapist. Over more than three years, the group included 20 members in total.
      This article describes a number of dreams recorded during a period when the group
      included seven members. Dreams helped the group members access their emotional
      pain, helplessness, yearning for a relationship with the deceased, guilt, and
      feelings of survival guilt. The transference-countertransference relationships
      were characterized by holding. Countertransference feelings of helplessness
      predominated. The therapist and the group as a whole contained various emotions,
      allowing the group members to return to the normal mourning processes from the
      parallel encouragement of group development and interpersonal relationships.

PMID- 24563939
TI  - "Women...mourn and men carry on": African women storying mourning practices: a
      South African example.
AB  - African mourning of loss of lives in South Africa has been shaped by discursive
      practices of both traditional African cultures and the sociopolitical
      developments under apartheid and in post-apartheid South Africa. This article
      reports on changes in mourning practices on the basis of a literature review and
      uses a collection of examples to highlight the navigation of some cultural and
      gendered issues relating to mourning, against the backdrop of the everyday
      experiences of loss of life in South Africa due to violence and HIV/AIDS. The
      article draws on African womanist and feminist scholarship and focuses on the
      intersections between cultural and gender practices of bereavement in the lives
      of professional urban African women. The authors argue for the use of positioning
      theory and witnessing practices to honor and story the ongoing struggle of
      African women as these women take different agentic positions by accepting,
      questioning, resisting, and/or changing cultural mourning practices while they
      compassionately witness the self and others in the narratives they live.

PMID- 24563940
TI  - African refugees in Egypt: trauma, loss, and cultural adjustment.
AB  - This study examined the influence of pre-immigration trauma on the acculturation
      process of refugees, as reflected in the manifestations of their continuing bonds
      with native cultures. Six African refugees who sought refuge in Egypt because of
      wars and political persecution were interviewed about the circumstances of their
      departure from their home countries, as well as their life experiences in Egypt.
      All participants kept continuing bonds with their native cultures, but these
      bonds manifested differently depending on their ability to assimilate pre
      immigration trauma and cultural losses. Participants who successfully assimilated
      both pre-immigration trauma and cultural losses developed continuing bonds with
      their native cultures that helped them (a) integrate the Egyptian culture into
      their life experiences and (b) tolerate difficult political conditions in Egypt.
      Participants who could not assimilate their pre-immigration trauma and cultural
      losses also developed continuing bonds with their native culture, but these bonds
      only provided them with solace.

PMID- 24563942
TI  - Self-injurious behavior and suicide attempts among Indonesian college students.
AB  - This study reports the prevalence of self-injurious behavior and suicide attempts
      among college students in Indonesia and examines risk factors distinguishing
      between 3 groups: self-injury with suicide attempt, non-suicidal self-injury, and
      non-self-injury. Self-report questionnaires measuring self-injury and suicide
      attempts, negative mood regulation expectancies (NMRE), depression, and childhood
      trauma were administered to 314 students. Of participants, 38% had deliberately
      injured themselves; among those, 21% also reported a suicide attempt. The 3
      groups differed significantly on NMRE, depression, and child neglect. More self
      injury and suicide attempts were associated with weaker NMRE and greater
      depression and child neglect.

PMID- 24563941
TI  - Psychological autopsy studies as diagnostic tools: are they methodologically
      flawed?
AB  - One of the most established "truths" in suicidology is that almost all (90% or
      more) of those who kill themselves suffer from one or more mental disorders, and
      a causal link between the two is implied. Psychological autopsy (PA) studies
      constitute one main evidence base for this conclusion. However, there has been
      little reflection on the reliability and validity of this method. For example,
      psychiatric diagnoses are assigned to people who have died by suicide by
      interviewing a few of the relatives and/or friends, often many years after the
      suicide. In this article, we scrutinize PA studies with particular focus on the
      diagnostic process and demonstrate that they cannot constitute a valid evidence
      base for a strong relationship between mental disorders and suicide. We show that
      most questions asked to assign a diagnosis are impossible to answer reliably by
      proxies, and thus, one cannot validly make conclusions. Thus, as a diagnostic
      tool psychological autopsies should now be abandoned. Instead, we recommend
      qualitative approaches focusing on the understanding of suicide beyond mental
      disorders, where narratives from a relatively high number of informants around
      each suicide are systematically analyzed in terms of the informants'
      relationships with the deceased.

PMID- 24563943
TI  - Death anxiety in persons with HIV/AIDS: a systematic review and meta-analysis.
AB  - One of the most commonly cited psychological sequelae of HIV/AIDS is anxiety
      regarding death due to the illness (i.e., death anxiety; DA). However, extant
      research is inconclusive on several empirical issues, such as DA's relation to
      HIV/AIDS diagnostic status, the impact of illness-related symptoms on DA, and
      factors that may protect against DA. We conducted a systematic review of the
      empirical literature and meta-analysis to answer specific questions concerning
      correlates of DA in persons with HIV/AIDS and important factors that may help
      explain variability in effect size estimates. The meta-analysis included 18
      studies (N = 1,757) examining DA in adults with HIV/AIDS. Meta-analytic findings
      indicated a small-to-medium effect of HIV/AIDS diagnostic status on DA, which was
      moderated by duration since diagnosis and by relation to the advent of highly
      active antiretroviral therapy. Results also indicated a small effect of illness
      related symptoms on DA, which was moderated by participant age. Social support
      and intrinsic religiosity were modest protective factors, but results indicated
      that extrinsic religiosity may exacerbate or be exacerbated by DA. Finally,
      results indicated a medium-to-large relation between psychological symptoms and
      DA. The implications of these results and other study findings are discussed.

PMID- 24563944
TI  - Reflections on jokes and cartoons about suicide.
AB  - This article is intended to engage others in a dialogue about the role and
      meaning of jokes about suicide. Types of jokes involving suicide are examined to
      distinguish the different types of humor involved. A sample of 118 recent
      political cartoons in an online website was downloaded, of which 73 concerned
      suicide bombers. Examples of suicide cartons and jokes involving disparagement,
      incongruity, repression, and ridiculousness are provided. Although in some
      contexts, such as suicidal terrorism, these themes may be appropriate, a few
      cartons and jokes that addressed ordinary suicidal individuals were often
      hostile.

PMID- 24563945
TI  - Continuing bonds after suicide bereavement in childhood.
AB  - It has been argued that the grieving process after suicide bereavement has unique
      properties (e.g.,J. R.Jordan, 2001). A qualitative study was conducted to explore
      one aspect of the grieving process--continuing bonds--after suicide bereavement
      in childhood. Data were collected through semi-structured interviews with 10
      suicide-bereaved children and analyzed using Interpretative Phenomenological
      Analysis (Smith & Osborn, 2003). Three themes are discussed: thinking about the
      deceased, coping strategies, and ongoing connections to the deceased. The
      findings highlight potentially unique qualities of continuing bonds after
      childhood suicide bereavement and factors that might influence their
      adaptiveness. Theoretical and clinical implications are outlined.

PMID- 24563946
TI  - Beyond knowledge and skills: self-competence in working with death, dying, and
      bereavement.
AB  - This study explored helping professionals' views on death work competencies. A
      total of 176 helping professionals were invited to state what the necessary
      competencies in death work are. Content analysis was conducted. Results showed
      that death work competencies can be categorized into 4 major areas: (a) knowledge
      competence, (b) practice competence, (c) self-competence, and (d) work
      environment competence. Self-competence was the most frequently mentioned by the
      participants. Self-competence was further categorized into 3 themes: (a) personal
      resources, (b) existential coping, and (c) emotional coping. Findings reflect
      helping professionals' emphasis on the role of self and personal preparation in
      doing death work. Implications on future death education and training for helping
      professionals were discussed.

PMID- 24563947
TI  - Faculty's empathy and academic support for grieving students.
AB  - This study assessed a voluntary sample (n = 123) of college faculty's attitudes
      toward grieving students and likelihood to provide referrals and course
      accommodations. Empathy levels of faculty were also measured. Although 97% of
      faculty indicated that at least 1 student had reported a death, only 36% had
      referred a student to counseling services. Mean number of referrals was .75,
      ranging 0 to 10. Empathy, attitude toward grief and a personal history of
      experiencing death during college were significant predictors of comfort level
      discussing death and likelihood to provide accommodations. Faculty were more
      likely to provide accommodations immediately following loss rather than weeks or
      months later.

PMID- 24563948
TI  - Contact with the dead, religion, and death anxiety among older Mexican Americans.
AB  - The purpose of this study is to see if contact with the dead is associated with
      lower death anxiety among older Mexican Americans. The data come from a
      nationwide survey of older Mexican Americans (N = 1,005). The study model
      specifies that (a) older Mexican Americans who have experienced contact with the
      dead are more likely to see the connectedness that exists among all people; (b)
      seeing that all people are one promotes feelings of grateful to God; (c)
      gratitude toward God is, in turn, associated with lower death anxiety. The
      findings support each of these relationships.

PMID- 24563949
TI  - Do reincarnation beliefs protect older adult Chinese Buddhists against personal
      death anxiety?
AB  - The aim of this exploratory survey study was to develop and validate a Buddhist
      reincarnation beliefs scale and explore the relation between Buddhist
      reincarnation beliefs and personal death anxiety in 141 older adult Hong Kong
      Chinese Buddhists. Buddhist reincarnation beliefs were unrelated to personal
      death anxiety. This suggests that not all religious afterlife beliefs have death
      anxiety buffering power as proposed by Terror Management Theory, perhaps because
      Buddhists view reincarnation not as a solace but rather as a renewal of
      sufferings due to unwholesome karma. Future cross-religion comparison studies
      could investigate the efficacy of reincarnation beliefs as a personal death
      anxiety defense mechanism in a Hindu sample.

PMID- 24563950
TI  - No criminal conviction for man who disclosed HIV.

PMID- 24563951
TI  - Education. Culturally-tailored programs show promise for reducing transmission.

PMID- 24563952
TI  - Treatment. 2 studies suggest positives of today's antiretroviral therapy.

PMID- 24563953
TI  - Black churches can have an impact on HIV prevention.

PMID- 24563954
TI  - ADA. HIV-positive woman fired for policy violation, not disability.

PMID- 24563956
TI  - Prisons.  Inmate fails to show right to privacy was violated by doctor.

PMID- 24563955
TI  - SSI.  ALJ failed to properly evaluate woman's medical records.

PMID- 24563957
TI  - Veteran failed to show HIV, hepatitis had service connection.

PMID- 24563958
TI  - Authors' reply.

PMID- 24563960
TI  - Author's response.

PMID- 24563959
TI  - Authors' reply.

PMID- 24563961
TI  - Author's response.

PMID- 24563962
TI  - Hereditary multiple exostosis.
AB  - Hereditary multiple exostosis is an intriguing genetic condition with a clinical
      impact in the field of orthopaedics, paediatrics and oncology. In this review we
      highlight the current knowledge about this condition from a clinical and
      scientific point of view. This gives us more insight into the molecular
      mechanisms and current models on which therapeutic agents are based. It allows
      for a multidisciplinary approach to the management of this complex condition.
      There is currently no exact pathological model that can accurately describe all
      the findings in the research on Hereditary Multiple Exostosis. Promising
      treatments with blocking agents are currently under investigation.

PMID- 24563963
TI  - Missed fractures in paediatric trauma patients.
AB  - Missed fractures and other occult musculoskeletal injuries are common in
      paediatric trauma patients despite the thorough evaluation with standard trauma
      protocols. Several factors have been identified that contribute to the risk of
      failing to identify these injuries during the initial resuscitation and
      assessment of the paediatric trauma patient. These include patient-related,
      clinical, technical, and radiological causes. Preventive strategies have been
      proposed to minimize these overlooked injuries and their potential long-term
      consequences. A timely review of this problem is appropriate to continually
      improve the quality of care delivered to paediatric trauma patients.

PMID- 24563964
TI  - Piriformis muscle rupture during total hip arthroplasty using a muscle-preserving
      posterior approach.
AB  - Total hip arthroplasty via muscle-sparing approaches is advocated and performed
      with increasing frequency. However, performing total hip arthroplasty through
      muscle-sparing approaches may require a more forceful retraction, which in turn
      may damage the muscles which the less invasive approach intended to preserve. We
      report on the rupture of the piriformis muscle during primary total hip
      replacement performed through a posterior approach intended to preserve this
      muscle. The prevalence and effects of such iatrogenic injuries are currently
      unknown, although unrecognised muscle damage may be a potential reason why early
      postoperative gait analyses could not demonstrate the expected benefits of less
      invasive surgery. Surgeons should be aware of this potential complication when
      performing total hip arthroplasty through a less invasive posterior approach.

PMID- 24563965
TI  - Treatment of massive rotator-cuff tears with a polyester ligament (LARS) patch.
AB  - We describe and analyse the results of our technique for repairing chronic
      massive tears (Goutallier grade 3 or 4) of the rotator cuff using a ligament
      augmentation and reconstruction system. This prospective, single surgeon series
      included 29 symptomatic patients (21 male, 8 female) with a mean age of 67.1
      years who underwent 31 ligament augmentation and reconstruction system procedures
      (two bilateral procedures) with a mean follow-up period of 3 years. All patients
      had clinical, radiographic, magnetic resonance imaging and arthroscopic evidence
      of a chronic massive rotator cuff tear. The primary outcome measure was assessed
      using the Oxford Shoulder Score and visual analogue score pre-operatively and at
      follow-up. Postoperative overall Oxford shoulder score and visual analogue score
      results demonstrated a statistically significant improvement at follow-up,
      compared with pre-operative values (p < 0.0001). Post-operative acromio-humeral
      interval showed a statistically significant increase when compared to pre
      operative radiographs (p = 0.0004). Two patients required revision with good
      postoperative results. We believe that, in the appropriate age group, the
      ligament augmentation and reconstruction system repair offers a good option for
      chronic, primary, non-closable rotator cuff defects in terms of pain relief and
      function.

PMID- 24563966
TI  - Surgical treatment algorithm for infected shoulder arthroplasty: a retrospective
      analysis of 17 cases.
AB  - There is no consensus regarding treatment of periprosthetic shoulder infections.
      We retrospectively reviewed 17 patients diagnosed with a periprosthetic shoulder
      infection. Patient demographics, preoperative diagnostics, therapeutic management
      and functional outcome were evaluated. The Constant-Murley score (CMS), Simple
      Shoulder Test (SST), Visual Analogue Score (VAS) and Disabilities of the Arm,
      Shoulder and Hand score (DASH) were used to assess clinical outcome. Pre-and
      intraoperative culture results and laboratory data, including C-reactive protein
      (CRP) and erythrocyte sedimentation rate (ESR), were analyzed. Three patients
      were treated by two-stage revision arthroplasty, 5 by resection arthroplasty with
      implantation of a cement spacer, 8 by resection arthroplasty without spacer and
      one patient underwent polyethylene exchange and serial debridement. The mean
      follow-up was 4.7 years (range : 1-93). The CMS was 27.8 for the resection
      arthroplasty group, 22.7 for the two-stage revision group and 20.6 for the
      resection arthroplasty with spacer group. No patients received chronic antibiotic
      suppression. Mean CRP value was 3.7 mg/L (range: 0.2 -11.1). Infection was
      monobacterial in 8 patients and polymicrobial in 9. The most common organisms
      were Coagulase negative staphylococcus (CNS) (13/17) and Propionibacterium spp.
      (7/17). Complications included two humeral fractures. At a mean follow-up of 4.7
      years, all but one patient were considered free of infection. Worst functional
      results were seen with the implantation of a definitive cement spacer. Two-stage
      revision arthroplasty remains the gold standard in chronic infections, but is
      associated with a high complication rate. One-stage revision to a reverse
      shoulder arthroplasty (RSA) is an attractive alternative in selected cases. A
      surgical treatment algorithm for infected shoulder arthroplasty is proposed.

PMID- 24563967
TI  - Humeral lengthening by distraction osteogenesis: a safe procedure?
AB  - This study was conducted to assess the safety of humeral lengthening using an
      Ilizarov frame. We retrospectively reviewed 26 humeral segments in 17 patients
      that were lengthened at our department between 1993 and 2011. There were varying
      aetiologies including achondroplasia, epiphyseal dysplasia, Oilier disease,
      trauma or infection of the proximal humeral growth-plate, unicameral bone cyst
      and brachial plexus injury. Mean age at start of surgery was 17.05 years (range :
      5-40). The mean lengthening achieved was 8.85 (3-13) cm. Mean lengthening
      percentage was 353% (range : 10-48). Average healing index was 30.56 days/cm
      (range : 17.46-4232). There was a significant difference in healing index between
      achondroplasia patients (28.79 days/cm) compared to others (33.41 days/cm). Minor
      problems included pin tract infection (14 segments). More important obstacles
      were temporary elbow flexion contracture (7 segments), premature consolidation (6
      segments), radial nerve dysaesthesia (6 segments) and loosening of a Schanz screw
      (1 segment). Complications included one fracture and one progressive bowing after
      frame removal. One planned lengthening was not completely achieved. Despite a lot
      of obstacles, humeral lengthening using an Ilizarov frame provided a reliable
      method to treat the functional or cosmetic problems of upper limb shortening.

PMID- 24563968
TI  - Which patients undergo a surgical reintervention following a distal radius
      fracture?
AB  - Not all malunited distal radius fractures cause pain or functional impairment,
      and only few patients require a surgical correction or a salvage procedure. The
      purpose of this retrospective study was to investigate differences between 38
      patients who underwent a reintervention and 65 patients who did not. The only
      discriminative variable in the current study was age : 46 years in the
      reintervention group versus 59 years in the non-reintervention group (p <
      0.0001). Differences in gender or type of malunion were not significant, and thus
      not discriminative. It can be concluded that patient age may be more often
      associated with a reintervention than gender or radiological characteristics of
      wrist fractures.

PMID- 24563969
TI  - Pyrocarbon spacer as a trapezium replacement for arthritis of the
      trapeziometacarpal joint; a follow-up study of 60 cases.
AB  - Rhizarthrosis is the most common degenerative joint disease of the hand,
      affecting about 10% of the population. We report our results with trapezium
      replacement using a pyrocarbon spacer. Between January 2005 and April 2010, 70
      patients underwent trapeziectomy with interposition of a pyrocarbon spacer. Sixty
      patients were examined at an average follow-up of 23.6 (5-64) months after the
      operation. Six (8.6%) of the 70 implanted pyrocarbon spacers dislocated. Based on
      the assessment scale devised by Buck-Gramcko, 19 patients achieved a very good
      outcome (31.6%), 31 patients (51.6%) had a good outcome, six results were
      satisfactory (10%) and four patients (6.6%) had a poor result. In this study,
      trapeziectomy and implantation of a pyrocarbon spacer achieved good or very good
      results in 83.2% of cases. The high cost of the implant and the observed rate of
      spacer dislocation should however be considered critically. While the short-term
      results of this method are encouraging, long-term outcomes will show whether this
      technique can keep up with the good results of suspension arthroplasty.

PMID- 24563970
TI  - Long-term results of the Sauve-Kapandji procedure in the rheumatoid wrist.
AB  - This retrospective long-term study evaluates the clinical and radiological
      results of the Sauve-Kapandji procedure in rheumatoid wrists. Fourteen patients
      with rheumatoid arthritis who had undergone a Sauve-Kapandji procedure were
      examined 10 to 16.5 years after surgery. Range of motion and grip strength were
      measured. The patients' complaints related with instability of the ulnar stump,
      the residual pain in the wrist, and the function of the operated hand were
      assessed. The review also included a radiological examination. Pain was found to
      have decreased and the gripping strength of the hand to have increased in all the
      patients. The range of wrist rotation was significantly improved. On radiographs,
      there were no signs of increased ulnar translation of the carpus. We noted no
      instance of subluxation or dislocation of the ulnar stump. In this long-term
      evaluation, the Sauve-Kapandji procedure was found to provide long-term
      improvement of the function of the wrist-hand complex, by eliminating the distal
      radio-ulnar joint which is a major source of pain in the rheumatoid wrist.

PMID- 24563971
TI  - Mid-term outcome of patients with pelvic and acetabular fractures following
      internal fixation through a modified Stoppa approach.
AB  - This retrospective study presents the mid-term outcome of polytrauma patients
      with pelvic ring and acetabular fractures operated using a modified Stoppa
      approach. We examined 32 patients (13 women and 19 men ; mean age 44 years) 24 to
      40 months after the trauma. We performed a functional assessment of these
      patients using Majeed's score. Mean Majeed score was 86.9 +/- 8.22 with a range
      from 70 to 100. Excellent clinical results were noted in 59% of cases (in 83% of
      pelvic fractures and 40% of acetabular fractures) and good clinical results in
      41% (in 17% of pelvic ring fractures and 60% of acetabular fractures). Fracture
      healing with anatomical reduction was achieved in all pelvic ring fractures.
      Healing with anatomic or satisfactory reduction was achieved in 90% of the
      acetabular fractures.

PMID- 24563972
TI  - Effect of surgical approach on the early outcome of total hip replacement for
      femoral neck fractures.
AB  - We reviewed the short-term outcome of 171 patients treated with total hip
      replacement for femoral neck fractures using the lateral (94 patients) or
      posterior approach (77 patients). The Sernbo score and the Abbreviated Mental
      Test Score were used to assess patients' pre-injury functional and cognitive
      status respectively. Patients were uniformly treated with regard to the type of
      prosthesis, size of femoral head and rehabilitation. They were followed up to a
      mean of 25 months (range : 13-42 months). The dislocation rate in the lateral
      group was 2.1% versus 0% in the posterior group. There was no difference with
      regards to leg length discrepancy and the restoration of medial offset. Our
      results were attributed the standardised patients' selection and adequate soft
      tissue repair.

PMID- 24563973
TI  - Total joint arthroplasty following intra-articular steroid injection: a
      literature review.
AB  - This study aimed to identify, by systematic review of the literature, whether
      intra-articular steroid injection before total joint replacement confers an
      increased risk of post-operative deep prosthetic infection. All studies assessing
      the incidence of deep prosthetic infection in patients who had undergone steroid
      injection in the same joint were included. A mixed meta-analysis and narrative
      review of 12 studies with 2068 participants was conducted. Steroid injection
      prior to total joint replacement was found to confer no increased risk of deep or
      superficial prosthetic infection (CI = 95%). We found no evidence of a link
      between injection and deep joint infection, and conclude that this is a safe
      procedure when conducted with aseptic precautions. We suggest a prospective
      randomised control trial to provide conclusive data on this question.

PMID- 24563974
TI  - Severe pelvic bone loss treated using a coned acetabular prosthesis with a stem
      extension inside the ilium.
AB  - We describe a modified surgical technique for the reconstruction of major
      acetabular defects using a coned acetabular component (the Stanmore 'ice-cream'
      cone prosthesis) and report its early clinical outcomes. A single surgeon
      performed 28 acetabular reconstructions using a stemmed-cone acetabular
      prosthesis (mean age 70.9 years; 61% female) in 15 oncology patients with
      periacetabular metastases and 13 patients requiring complex arthroplasty
      procedures. Defects were graded using the Paprosky classification (10 = 3A; 8 =
      3B; 10 = pelvic discontinuity). All procedures were performed without fluoroscopy
      using an extended posterior hip approach. Mean operative time (including
      anaesthesia) was 133 minutes; there were no intraoperative complications.
      Postoperative complications had occurred in 14% (n = 4), at a mean follow-up of
      12.5 months (range: 2-33 months). There were no failures in patients with pelvic
      discontinuity. The stemmed-cone acetabular prosthesis was found to provide a
      useful method for acetabular reconstruction (including pelvic discontinuity) in
      both complex oncological and hip arthroplasty cases.

PMID- 24563975
TI  - High incidence of intraoperative anchorage failure in FasT-fix all inside
      meniscal suturing device.
AB  - The aim of this study was to assess the incidence of intraoperative failure of
      the FasT-fix (Smith & Nephew, Andover, USA) device for all-inside meniscal repair
      and to investigate any underlying factors. Searching retrospectively the hospital
      databases and patient files, we collected 78 cases, totalling 61 successes and 17
      failures. Of a total of 190 FasT-fix anchors, 22 failed (a calculated incidence
      of 11.6%), either by anchorage slippage through the capsule during tightening or
      by failure of anchor deployment.

PMID- 24563976
TI  - Improving tibial component coronal alignment using clearly defined anatomical
      structures in total knee arthroplasty.
AB  - Several authors recently proposed to use clearly defined anatomical structures
      for extramedullary tibial alignment in total knee replacement, instead of using
      the intermalleolar center. The purpose of this study was to evaluate the benefits
      of using the dorsalis pedis artery and the anterior tibial crest as distal
      landmarks. Postoperative radiographs in 195 knees (98 in the control and 97 in
      the landmark group) were evaluated. The mean coronal alignment of the tibial
      component was 89.7 degrees +/- 2.1 degrees in the control group and 90.0 degrees
      +/- 1.3 degrees in the landmark group. Although there was no significant
      difference, the proportion of radiological outliers was significantly reduced in
      the landmark group compared to the control group (6.2% vs 27.6% in > 2 degrees
      outliers; p < 0.0001, 1.0% vs 10.2% in > 3 degrees outliers; p = 0.01). In order
      to achieve accurate coronal alignment of the tibial component, it appears better
      to use multiple clear anatomical landmarks such as the dorsal pedis artery and
      the anterior tibial crest rather than using only the intermalleolar center.

PMID- 24563977
TI  - Conversion of unicompartmental knee arthroplasty to total knee arthroplasty: the
      challenges and need for augments.
AB  - The potential advantages of unicompartmental knee arthroplasty (UKA) include
      lower morbidity and mortality, quicker recovery, good range of motion, good
      medium and long-term survival results, potential bone conservation and perceived
      easier revision. Converting a UKA to a total knee arthroplasty (TKA) may be
      challenging due to issues of bone loss, need for augmentation, restoring joint
      line and rotation. We present the intraoperative findings of 201 cases of failed
      UKA's from the Trent Wales arthroplasty audit group (TWAAG) register. The
      objectives of the study were to determine the modes of failure, number of cases
      requiring augments and bone grafting, types of augments and implants used in
      revision surgery. This study does not include the clinical outcomes after
      revision knee surgery. The average age of the cohort at revision surgery was 67
      years. There were 111 females and 90 males. The commonest modes of failure in
      young patients were unexplained pain/instability and aseptic loosening and in
      older patients they were aseptic loosening and progression of the disease. The
      survivorship of the implant was higher in the less than 55 years age group in
      comparison to the older patients. A total of 49 patients (25.9%) required bone
      grafting commonest in the 60 years and above age group (79.6%). Fifty patients
      (26.4%) required some form of augmentation, with the commonest site being tibia
      and commonest augment being tibial stem (35 cases). Only 8% of the cohort
      required revision knee implants whereas 78% of the cases received a cruciate
      retaining primary knee implant. To the author's knowledge, this is one of the
      largest studies in the literature which signifies the technical difficulties that
      might be experienced in revising the UKA's which will require appropriate pre
      operative planning.

PMID- 24563978
TI  - Ilizarov trifocal lengthening followed by intramedullary nailing for massive
      posttraumatic tibial bone defects.
AB  - The treatment of massive tibial bone defects takes a very long time. An Ilizarov
      trifocal approach decreases the lengthening time. Subsequent intramedullary
      fixation decreases the complications of the conventional Ilizarov method. This
      technique was applied between June 2010 and June 2011 in 10 male patients with a
      mean age of 30 years. All had grade III open tibial fractures. The patients were
      treated at Mansoura University Hospital and a private hospital. The sequence of
      treatment included trifocal lengthening using the Ilizarov method, followed by
      removal of the fixator, temporary plaster cast immobilisation and subsequent
      intramedullary fixation until complete union was achieved. The length of the
      tibial bone defect ranged between 6-12 cm; the lengthening time ranged between 45
      75 days and the consolidation time ranged between 90-160 days. The results were
      evaluated according to Paley's bone and functional assessment scores. The bone
      results were excellent in 7 patients and good in 3. Two patients had non union
      and one patient had pin tract infection. The functional results were excellent in
      7 patients and good in 3. Two patients had equinus deformity and one patient had
      limited range of knee motion. There were no deep infections, DVTs or leg length
      discrepancies greater than 2.5 cm. Ilizarov trifocal lengthening followed by
      delayed intramedullary fixation appeared in this study as a good method of
      treatment for massive posttraumatic tibial bone defects. It reduced fixator time
      and minimized the complications associated with the Ilizarov fixation.

PMID- 24563979
TI  - Percutaneous autogenous bone marrow injection for delayed union or non union of
      fractures after internal fixation.
AB  - The aim of this study was to assess the results of percutaneous injection of
      autologous bone marrow in the treatment of fractures presenting with delayed
      union or non union after internal fixation. Twenty consecutive patients
      presenting to our outpatient clinic with internally fixed fractures with delayed
      union or non union were included in the study. The time between the index surgery
      and the bone marrow injection ranged from 4 to 24 months with a mean of 9.65
      months. The bone marrow aspirate was injected percutaneously into the fracture
      site under fluoroscopy control. Nineteen out of the twenty fractures achieved
      clinical and radiological union, on average after 2.95 months. In this series,
      percutaneous bone marrow injection appeared as a simple and effective method to
      accelerate fracture healing in patients with delayed union and nonunion of
      fractures.

PMID- 24563980
TI  - Treatment of thoracolumbar burst fractures: short-segment pedicle instrumentation
      versus kyphoplasty.
AB  - The management of amyelic thoracolumbar burst fractures remains controversial. In
      this study, we compared the clinical efficacy of percutaneous kyphoplasty (PKP)
      and short-segment pedicle instrumentation (SSPI). Twenty-three patients were
      treated with PKP, and 25 patients with SSPI. They all presented with Type A3
      amyelic thoracolumbar fractures. Clinical outcomes were evaluated by a Visual
      Analog Scale (VAS) and Oswestry Disability Index (ODI) preoperatively,
      postoperatively, and at two years follow-up. Radiographic data including the
      anterior and posterior vertebral body height, kyphotic angle, as well as spinal
      canal compromise was also evaluated. The patients in both groups were similar
      regarding age, bone mineral density (BMD), follow-up period, severity of the
      deformity and fracture. Blood loss, operation time, and bed-rest time were less
      in the PKP group. VAS, ODI score improved more rapidly after surgery in the PKP
      group. No significant difference was found in VAS and ODI scores between the two
      groups at final follow-up (p > 0.05). Meanwhile, the height of anterior vertebrae
      (Ha), the height of posterior vertebrae (Hp) and the kyphosis angle showed
      significant improvement in each group (p < 0.05). The postoperative improvement
      in spinal canal compromise was not statistically significant in the PKP group (p
      > 0.05); there was a significant improvement in the SSPI group (p < 0.05).
      Moreover, these postoperative radiographic assessments showed significant
      differences between the two groups regarding the improvement of canal compromise
      (p < 0.05). At final follow-up, remodeling of spinal canal compromise was
      detected in both groups. CONCLUSION: Both PKP and SSPI appeared as effective and
      reliable operative techniques for selected amyelic thoracolumbar fractures in the
      short-term. PKP had a significantly smaller blood loss and shorter bed-rest time,
      but SSPI provided a better reduction. Long-time studies should be conducted to
      support these clinical outcomes.

PMID- 24563981
TI  - Outcomes of conservative treatment for ruptured lumbar disc herniation.
AB  - The authors set up a prospective study of the effect of conservative treatment on
      a ruptured lumbar disc herniation in 89 patients, between June 2008 and June
      2010. Seventy-two patients (81%) improved, while the other 17 (19%) needed
      surgery. The JOA score (best possible result: 29) was found to be significantly
      improved in the 72 patients of the conservative group, at 1 month, 3 months, 6
      months, 1 year and 2 years (t-test: p < 0.001). At final follow-up, after 2
      years, 84.7% of the patients in the conservative group had a good or excellent
      result. However, if the 17 surgical cases were included, this proportion dropped
      to 68.5%. The volume of the protrusion decreased significantly in the 72 patients
      of the conservative group: from 1422.52 +/- 539.10 mm3 to 102735 +/- 585.51 mm3
      (paired t-test: p < 0.001). There was a definite correlation, in the conservative
      group, between the final resorption rate on the one hand and the percentage of
      combined excellent and good results on the other hand (72 cases; Spearman rank
      correlation coefficient: r 0.01 = 0.470, p < 0.001).

PMID- 24563983
TI  - Temporary external fixation facilitates open reduction and internal fixation of
      intra-articular calcaneal fractures.
AB  - Management of intra-articular calcaneal fractures during the past years has
      ranged from the nihilistic approach of no active treatment to open reduction and
      internal fixation or even to early subtalar arthrodesis. Operative treatment
      presents the surgeon with many challenges. Good results require atraumatic
      exposure, anatomic reduction, rigid fixation and early mobilization. We describe
      the use of a temporary external fixator as an intraoperative aid in the open
      reduction and internal fixation of intra-articular calcaneal fractures. We
      propose this operative strategy as an option for the treatment of calcaneal
      fractures. The controlled distractive force provides numerous benefits. These
      include improved exposure of the subtalar joint, correction of angulation and
      maintenance of temporary stability prior to definitive fixation. We have found
      this technique applicable and easily reproducible.

PMID- 24563982
TI  - Giant cell tumour of bone in the appendicular skeleton: an analysis of 276 cases.
AB  - This retrospective study analyzed 276 cases of giant cell tumour of bone in the
      appendicular skeleton of patients first diagnosed and treated at the Orthopaedic
      Department of the West China Hospital in Sichuan University between 1988 and
      2007. Fifty-eight percent of the tumours involved the knee region. The most
      common primary treatment was curettage (162 patients) combined with adjuvant
      local therapy. The effects of bone cement (PMMA), high-speed burring, electro-
      cauterization, liquid nitrogen, and phenol on the recurrence rate were also
      analyzed. The differences in local recurrence rates were analyzed between giant
      cell tumours confined to bone (Campanacci grades I and II) and giant-cell tumours
      with extraosseous extension (Campanacci grade III) treated with intralesional
      curettage. The recurrence rate of patients who received the first treatment at
      our institution was 11.2%. Recurrence was observed in 31 cases and multiple
      recurrences were observed in 5 cases. Treatment included intralesional curettage
      (173%), marginal excision (143%), wide excision (1.9%), or radical resection
      (0%). Metastases, which mainly involved the lung, occurred in 6 cases (2.2%).
      There was a significantly lower recurrence rate (p = 0.004) following
      intralesional curettage combined with high-speed burring (n = 102) as compared
      with intralesional curettage without high-speed burring (n = 60). Although the
      efficacy of liquid nitrogen and electrocauterization did not reach significance,
      they seem to have a similar effect to high-speed burring. Therefore, we recommend
      high-speed burring as a necessary adjuvant therapy. The combination of all
      adjuvants (burring, liquid nitrogen, and electro-cauterization) is recommended as
      a standard treatment. Cement filling of the cavity after curettage was not widely
      used in this series, but its merits have been reported in several studies; we
      therefore recommend that cement filling should be added to the adjuvants to be
      used after burring, liquid nitrogen and/or electrocauterization.

PMID- 24563984
TI  - Leadership roles allow physicians to make a difference.

PMID- 24563985
TI  - Be the flex in medicine's muscle for 2014.

PMID- 24563986
TI  - AMA meeting forging toward an SRG fix.

PMID- 24563987
TI  - Interesting statistics about the U.S. health care system.

PMID- 24563988
TI  - The current state of ICD-10 & preparing for it.
AB  - The AMA continues to harbor serious concerns and reservations with the
      significant burden of the ICD-10 mandate and continues to convey these points to
      policymakers in Washington. The AMA is well aware of the concerns of physicians
      related to the growing number of burdens being placed on their practices, of
      which ICD-10 is a large one, and continues to advocate for overall regulatory
      relief. While the AMA has been working for many years to hold back the
      implementation of ICD-10, at this time, it does remain a regulatory mandate.
      Because of this, it is important that physicians prepare for its implementation
      in order to avoid the rejection of claims and cash flow interruptions.

PMID- 24563989
TI  - Now playing at your local state capitol.

PMID- 24563991
TI  - Burnout.

PMID- 24563990
TI  - We can do better than work restrictions.

PMID- 24563992
TI  - Missouri physicians do not stand alone.

PMID- 24563993
TI  - Getting comfortable with death. The good death: dying to get it right.

PMID- 24563994
TI  - Getting comfortable with near death experiences. An overview of near-death
      experiences.

PMID- 24563995
TI  - Do business considerations & bottom line finances trump quality medical care and
      service in hospitals' administration?

PMID- 24563996
TI  - Just don't sit there--do something!

PMID- 24563997
TI  - A milestone in medical history. German Medical Association finally apologizes for
      atrocities committed by German physicians under the Nazis.

PMID- 24563998
TI  - Physicians need to ponder & plan their own end of life care decisions.

PMID- 24563999
TI  - On death & dying.

PMID- 24564000
TI  - CDC physician comments raise concern: post-antibiotic era not here yet.

PMID- 24564001
TI  - Omega-3 polyunsaturated fatty acids for the prevention of cardiovascular disease:
      do formulation, dosage & comparator matter?
AB  - Multiple trials over the past two decades testing omega-3 polyunsaturated fatty
      acids (PUFAs), containing eicosapentaenoic acid (EPA) and or docosahexaenoic acid
      (DHA), have shown substantial benefits for reducing major coronary heart disease
      (CHD) events, all-cause mortality, cardiovascular (CV) death, sudden cardiac
      death (SCD), and stroke. However, recent trials testing omega-3s have generally
      failed to confirm these benefits. While increased fish and fish oil intake among
      the general population, increased use of optimal medical therapy (including
      statins, aspirin, and modern antihypertensive medications) probably make it more
      challenging for fish oil supplementation to show additional benefits, there might
      be further explanations in the formulation, dosage, and comparator used in these
      recent omega-3 trials.

PMID- 24564002
TI  - Obesity: the 'huge' problem in cardiovascular diseases.
AB  - Obesity is an epidemic in the United States. It is an independent risk factor for
      cardiovascular diseases and associated with reduced life expectancy. The adverse
      effects are related to direct impact of obesity on cardiovascular system and
      indirectly through its influence on risk factors. Excessive accumulation of
      adipose tissue in the myocardium leads to structural and functional alteration.
      In addition, numerous hormones secreted by adipose tissue create pro-inflammatory
      and prothrombotic state. This predisposes to coronary heart disease, heart
      failure, and sudden death. Even those with normal weight but excessive body fat
      are at risk. Weight reduction and exercise are the main therapeutic options.

PMID- 24564003
TI  - The burden of chronic diseases in Missouri: progress and challenges.
AB  - Chronic diseases are the major causes of premature death, disability and loss of
      quality of life in Missouri. The prevalence of many chronic diseases, conditions
      and risk behaviors is greater in Missouri than the U.S. The medical costs for
      treating chronic diseases are a burden on the state's economy and will increase
      as the population ages. Prevention and control of chronic diseases is essential
      to the physical and economic health of Missourians.

PMID- 24564004
TI  - Elder abuse: golden years' lost luster.

PMID- 24564005
TI  - More than just a pill. How to include psychosocial approaches sin the treatment
      of anxiety & depressive disorders.
AB  - Anxiety and depressive disorders are the most common psychiatric disorders,
      causing high personal and economic burden. Psychosocial approaches, such as
      psychotherapy or mind-body instruction, along with self-help approaches,
      exercise, and proper sleep hygiene are effective solo or additive (to
      pharmacotherapy) strategies. Many physicians are less familiar with these methods
      for treating anxiety/depressive disorders. This article seeks to illuminate
      psychosocial approaches for depression and anxiety that act additively or
      independently of pharmacotherapy and explain how physicians can utilize them.

PMID- 24564007
TI  - The evolution of ANA/KNA promises a bright future.

PMID- 24564008
TI  - Data bits "that blood pressure machine doesn't work right on me"!

PMID- 24564009
TI  - Lesbian, gay, and bisexual adolescent suicidality: the impact of social stigma.

PMID- 24564010
TI  - Complementary treatment options for childhood and adolescent attention
      deficit/hyperactivity disorder.

PMID- 24564006
TI  - Medical and recreational marijuana: commentary and review of the literature.
AB  - Recent years have seen substantial shifts in cultural attitudes towards marijuana
      for medical and recreational use. Potential problems with the approval,
      production, dispensation, route of administration, and negative health effects of
      medical and recreational marijuana are reviewed. Medical marijuana should be
      subject to the same rigorous approval process as other medications prescribed by
      physicians. Legalizing recreational marijuana may have negative public health
      effects.

PMID- 24564011
TI  - Appreciative inquiry: an emerging approach to delivering quality nursing care.

PMID- 24564012
TI  - I do make a difference.

PMID- 24564013
TI  - The road to legislative mandate of HPV vaccination in Kentucky.
AB  - HPV vaccination is a national issue relevant to health promotion and cancer
      prevention. Policy mandating vaccination has been mostly unsuccessful, but
      success has been achieved through improved public awareness and communication
      nationwide. Kentucky has had successes in HPV legislation; however, continued
      advocacy is needed to support parents, encourage young adults, and support the
      endeavors of other state policy makers.

PMID- 24564014
TI  - Access to healthcare: removing barriers for the APRN.
AB  - As nurses face changes in the healthcare arena, we must be aware and involved in
      the legislation that affects our delivery of care to our clients. While many do
      not perceive their ability to influence legislative matters, there are things we
      can do. Such endeavors can include inviting legislators to APRN's practice,
      encouraging clients to talk with their legislators, and share evidence-based
      information on the outcomes of APRN practice. Nursing is a strong profession and
      has faced many challenges in the past. Nursing now needs to advocate for our
      profession and thus provide a positive impact on the healthcare of the clients.

PMID- 24564015
TI  - Looking forward. Is Congress willing to correct the flawed sustainable growth
      rate?

PMID- 24564016
TI  - Medicare reform: a look at the house ways and means proposal.

PMID- 24564017
TI  - Merging Medicare Parts A and B: potential effects on beneficiaries, surgeons, and
      other stakeholders.
AB  - Describes the reasons Medicare Parts A and B are currently paid under different
      mechanisms Explains why the time is ripe to merge Parts A and B Examines the
      potential effects on delivery of patient care, the federal government, and
      providers

PMID- 24564018
TI  - 2014 fee schedule and CPT code changes will affect surgical practice.
AB  - An overview of provisions in the Medicare physician fee schedule final rule and
      changes in CPT coding that will affect physician reimbursement in 2014. Key
      elements of the final rule for the fee schedule center on the potential reduction
      in payment due to the conversion factor update, payment for in-office procedures,
      PQRS reporting options, public reporting via CMS' Physician Compare website, and
      the value-based payment modifier. Fundamental changes in CPT coding affect
      consultation codes, drainage of skin and subcutaneous structures, complex repair,
      skin flaps and grafts, breast biopsies and imaging, and other surgery-related
      codes.

PMID- 24564019
TI  - Will acute care surgery and surgicalists help to avert an emergency care crisis?

PMID- 24564020
TI  - Repealing the SGR.

PMID- 24564021
TI  - The quest for safe surgical care: are we missing the obvious?

PMID- 24564022
TI  - Less invasive option for small hepatocellular carcinoma: thermal ablation as
      first-line therapy?

PMID- 24564023
TI  - 2013 Pediatric Report: pediatric consumers.

PMID- 24564024
TI  - [How I treat...a red eye].
AB  - Before any initiation of treatment for a red eye, an accurate differential
      diagnosis must absolutely be done, as considered in a previous article. Red eye
      can result from benign diseases, but also from serious pathologies which
      shouldn't be neglected, as they require a rapid ophtalmologist management. This
      is the case for keratitis, uveitis, acute glaucoma attack, or endophtalmitis.
      Treatment of red eye will just be symptomatic in benign diseases but, in
      contrast, will absolutely need an etiological diagnosis and therapeutic approach
      in more serious cases. Generally speaking, topical steroids should never be
      prescribed in doubt of infectious keratitis. Moreover, local anaesthetics,
      because of their toxicity for the cornea, should not be prescribed under any
      circumstances.

PMID- 24564025
TI  - [Is this cerebral cavernoma the cause of a Parkinsonian syndrome?].
AB  - We report the case of a patient presenting with an akineto-rigid syndrome of the
      left hemibody whose etiological exploration by magnetic resonance imaging showed
      the presence of a cavernoma located in the right lenticular region. The interest
      of this situation is to establish if there is a pathophysiological link between
      such symptoms and the lesion revealed by the MRI.

PMID- 24564026
TI  - [European guidelines for the management of diabetes, prediabetes and
      cardiovascular disease. Second part. Managemnet of cardiac, cerebrovascular and
      peripheral artery complications].
AB  - Patients with predliebetes (dysglycaemia) or diabetes present accelerated
      atherosclerosis that predisposes them to multiple cardiovascular complications.
      We summarize here the joint recommendations recently published by the European
      Society of Cardiology and the European Society for the Study of Diabetes. The
      management of main risk factors, aiming to optimize primary or secondary
      prevention, has been developed in a first article. This second article Is
      focusing on the management of cardiac, cerebrovascular and peripheral
      arteriopathic complications. The importance of an individualized patient-centered
      strategy is emphasIzed, including the management of microanglopathies and,
      ideally within a multidisciplinary approach.

PMID- 24564027
TI  - [Illustrated literature review of peripartum cardiomyopathy].
AB  - Peripartum cardiomyopathy is defined by the development of heart failure with
      left ventricular systolic dysfunction at the end of pregnancy or in the months
      following childbirth. Its diagnosis remains difficult due to lack of specificity.
      Its pathophysiology is still imperfectly understood, but involves both genetic
      and pregnancy related factors. From a therapeutic viewpoint, the recommendations
      of the European Society of Cardiology on heart failure are used, but the stage of
      pregnancy must be taken into account for the treatment choice. The chances of
      recovery are greater than in other non-ischemic cardiomyopathies. However, an
      early diagnosis remains crucial to increase the probability of recovery
      particularly with bromocriptine, which has shown positive results in recent
      years.

PMID- 24564028
TI  - [Differential role of physical activity and diet in the prevention of childhood
      obesity: pre-eminence of physical activity].
AB  - The current theory, known as the "theory ofenergy balance", perceives paediatric
      obesity, like adults' obesity, as the result of an excessively positive energy
      balance. Thus, prevention endeavours have focused on controlling calories intake
      and dietary education, with increases in physical activity (PA) having just a
      supporting role. Paradoxically, preventive programmes developed with this vision
      are not satisfactory, whereas some recent findings suggest, that in the growing
      body of youths, PA may stimulate stem cells to differentiate preferentially into
      lean tissue. These observations advocate the emergence of a new theoretical
      framework to childhood obesity prevention: the "developmental theory", which
      posits the pre-eminence of PA. As a result, preventive strategies that would
      emphasise vigorous PA rather than food intake control can help youths develop
      lean bodies, at the same time that they ingest sufficient amounts of the energy
      and accompanying nutrients needed for a healthy growth.

PMID- 24564029
TI  - [Mutism].
AB  - Mutism is a symptom we see in consultation for an absence or lack of langage
      acquisition and/or for relationship problems (isolation, withdrawal, crisis when
      breaking up) alerting the family. The differential diagnosis is complex and
      mutism can be symptomatic of several personality psychopathological structures.
      After a literature review, we shall describe three clinical cases and discuss the
      difficult approach to this symptom, its psychopathological features, as well as
      its pronostic and therapeutic aspects".

PMID- 24564030
TI  - [OCEBM levels of evidence system].
AB  - The hierarchy of evidence from medical research is a key concept in evidence
      based medicine (EBM). In 1998, the Oxford Centre for Evidence-Based Medicine
      published a levels table based on study designs. An updated and more user
      friendly version, published in 2011, focuses on the issues of prevalence,
      diagnosis, prognosis, treatment and screening. This paper presents and discusses
      this approach.

PMID- 24564031
TI  - [The MAP kianase cascade. A key target for treatments in skin cancerology].
AB  - Intracellular mitogen-activated protein kinases (MAPK) form a signalling cascade
      of proteins involved in cell proliferation, differentiation, migration and
      apoptosis. They are particularly activated by some cytokines, hormones,
      environmental stress and in skin cancers as well. A series of pharmacological
      compounds targeting the MAPK cascade dramatically changes skin cancerology, at
      least during a transient phase of the metastatic process. Some combined
      treatments possibly increase the median overall survival.

PMID- 24564032
TI  - [Dapoxetine (Priligy): on demand treatment of premature ejaculation].
AB  - Premature ejaculation (PE) is a common sexual dysfunction, affecting
      approximately 20-24% of men. Managing PE has been a challenge for physicians and
      psycho-sexologists as well because no drug for PE has been approved by European
      (EMA) or U.S. (FDA) drug agencies. Over the past decade, clinical evidence has
      emerged indicating a beneficial effect of selective serotonin reuptake inhibitors
      (SSRIs), tramadol, penile anesthesia and, in some cases, inhibitors of
      phosphodiesterase type 5 for the treatment of men with PE. A psycho-sexological
      care helps support. In spite of their efficacy, adverse effects represent the
      major concern for the chronic use of SSRIs in patients with PE and they may
      prompt discontinuation from therapy. Dapoxetine, marketed as Priligy, is the
      first compound developed specially for the treatment of PE, on demand before
      intercourse. Dapoxetine works by inhibiting the serotonin transporter, increasing
      serotonin's action at the postsynaptic cleft, and as a consequence promoting
      ejaculatory delay. Dapoxetine is quickly absorbed and eliminated rapidly from the
      body. Its fast acting property makes it suitable for the on demand treatment of
      PE.

PMID- 24564033
TI  - Possible economic gains from cancer research.

PMID- 24564034
TI  - Prevalence of overweight and obesity among children six to ten years of age in
      the north-east health region of Jamaica.
AB  - OBJECTIVE: To estimate the prevalence and correlates of overweight and obesity
      among children six to ten years old in the North-East Health Region (NEHR)
      ofJamaica. METHODS: Weights and heights were measured in a representative sample
      of 5710 children between the ages of six and ten years in 34 schools between
      October 2008 and March 2009. Overweight and obesity were defined as body mass
      index (BMI) Z-score > 1SD and >2SD, respectively based on the World Health
      Organization (WHO)-endorsed age and gender-specific growth standards for
      children. Point prevalence estimates of overweight and obesity were calculated.
      Odds ratios (OR) and 95% confidence intervals (CI) were used to estimate
      associations between overweight and obesity and age, gender and school location.
      RESULTS: Overweight and obesity prevalence among children six to ten years old in
      NEHR, Jamaica, was 10.6% and 7.1%, respectively. Overweight (OR = 1.11, 95% CI:
      1.04, 1.18) and obesity (OR = 1.17, 95% CI: 1.08, 1.26) prevalence increased
      significantly with age. Overweight (OR = 1.51, 95% CI: 1.27, 1.80) and obesity
      (OR = 1.36, 95% CI: 1.11, 1.67) prevalence was significantly higher among girls
      than boys. Children attending rural-public schools had less risk of being
      overweight (OR = 0.57, 95% CI: 0.46, 0.70) and obese (OR = 0.35, 95% CI: 0.28,
      0.44) when compared with urban-public schools and private schools. Both
      overweight (OR = 2.11, 95% CI: 1.60, 2.78) and obesity (OR = 1.68, 95% CI: 1.24,
      2.28) were significantly more common among children attending private schools.
      After adjusting for age and gender the results still remained statistically
      significant. CONCLUSIONS: Overweight/obesity prevalence among children six to ten
      years old in NEHR of Jamaica is 17.7% with older children and girls having higher
      rates. Children attending urban-public and private schools have higher prevalence
      than those attending rural schools. Appropriately targeted interventions are
      needed to combat this problem.

PMID- 24564035
TI  - In vitro and in vivo anti-cancer effects of tillandsia recurvata (ball moss) from
      Jamaica.
AB  - OBJECTIVE: Tillandsia recurvata, also commonly known as Ball Moss, is endemic to
      Jamaica and some parts of the Caribbean and South America. The plant, despite
      being reported to be used in folk medicine, had not previously been evaluated for
      its anti-cancer potential. The aim of this study was to evaluate the anti-cancer
      activity ofBall Moss. METHODS: The anti-proliferation activity of the crude
      methanolic extract of the T recurvata was evaluated in vitro in five different
      histogenic cancer cell lines (prostate cancer - PC-3, breast cancer Kaposi
      sarcoma, B-16 melanoma and a B-cell lymphoma from a transgenic mouse strain)
      using the trypan blue assay. The crude extract was also evaluated in vivo in
      tumour-bearing mice. Immunohistochemistry staining with Apoptag was used for
      histology and determination of apoptosis. RESULTS: The crude methanolic extract
      of T recurvata demonstrated anti-proliferation activity against all the cell
      lines, killing > 50% of the cells at a concentration of 2.5 microg/ml. Kaposi
      sarcoma xenograft tumours were inhibited by up to 75% compared to control in the
      in vivo study (p < 0.05). There was evidence of DNA fragmentation and a decrease
      in cell viability on histological studies. The methanolic extract showed no toxic
      effect in the mice at a dose of 200 mg/kg. CONCLUSIONS: Our data suggest that T
      recurvata has great potential as an anti-cancer agent and that one of its
      mechanisms of cell kill and tumour inhibition is by the induction of apoptosis.

PMID- 24564036
TI  - Predicting 24-hour urinary sodium excretion in Afro-Caribbean Barbadians by
      comparing urine sodium excretion over different durations versus spot collection.
AB  - AIM: Urinary sodium excretion is used as an assessment tool for salt intake and
      salt handling. Even though cumbersome, the most reliable and readily used method
      in clinical and epidemiological studies is the 24-hour urine collection. This
      study investigates other appropriate means ofpredicting 24-hour urinary sodium
      excretion in a sample of Afro-Caribbeans in Barbados by assessing the correlation
      of actual and estimated urinary sodium excretion between a 24-hour urine
      collection sample, 12-hour (AM and PM), and spot (AM and PM) urine collections.
      METHOD: A convenient sample of 30 healthy participants of Afro-Caribbean origin
      between the ages of 21 and 55 years was recruited for the study. The 24-hour
      urine samples and anthropometric data were collected as documented in the study's
      standard clinical procedure. A 24-hour urine sample was collected as two separate
      12-hour AM and PM samples. In addition, two spot samples (AM and PM) were taken
      during each 12-hour sample collection period. Analysis of the urinary sodium and
      creatinine was done with a Roche/Hitachi Modular System (Roche Diagnostics, IN,
      USA). SPSS version 19 was used to analyse the data to make inferences. RESULTS:
      Thirty Afro-Caribbean subjects participated in this study: 16 females and 14
      males. The average age and body mass index (BMI) were 38 +/- 17 years and 25.32
      +/- 5.98 kg/m2, respectively. The greatest correlation of the estimated 24-hour
      sodium excretion to the measured 24-hour sodium excretion was observed in the 12
      hour PM sample (Pearson's correlation, r = 0.786, p < 0.001) followed by the 12
      hour AM sample (Pearson's correlation, r = 0.774, p < 0.001). The PM spot sample
      showed a weaker, but still statistically significant correlation to the 24-hour
      timed sample (Pearson 's correlation, r = 0.404, p < 0.045). The AM spot sample
      showed a very weak and insignificant correlation (Pearson 's correlation, r =
      0.05, p = 0.807) to the 24-hour timed sample. Similarly to the whole sample, the
      gender analysis demonstrated that estimated 24-hour sodium excretion in the
      female's 12-hour PM sample had the greatest correlation (r = 0.819, p < 0.001) to
      the measured 24-hour sodium excretion, followed by the 12-hour AM (r = 0.793, p =
      0.001) and the PM spot samples (r = 0.741, p = 0.02). The correlation between
      variables is weaker in males compared to the females. CONCLUSION: Overall, this
      study shows a clear correlation between the estimated 24-hour sodium excretion
      from the 12-hour timed PM sample and the measured 24-hour sodium excretion. Such
      findings support the thought of using other alternatives to determine sodium
      excretion, in view of replacing the cumbersome 24-hour urinary collection with a
      smaller timed sample. Nonetheless, a more robust and randomized population sample
      as well as a method to correct for high creatinine variability is required to
      further enhance the significance of the obtained results.

PMID- 24564037
TI  - Evaluation of paediatric patients with protein losing enteropathy a single centre
      experience.
AB  - OBJECTIVE: The aim of the study is to evaluate paediatric patients with protein
      losing enteropathy (PLE). METHODS: Fourteen cases diagnosed as PLE were evaluated
      in terms ofaetiologies, diagnostic methods, laboratory findings, treatment
      procedures and long-term prognosis. RESULTS: Four of the cases had coeliac
      disease, three intestinal lymphangiectasia, three giardia infection, one H pylori
      infection and three cytomegalovirus (CMV) infection. Histopathological
      examinations of duodenum specimens revealed total villous atrophy in four cases,
      lymphatic dilatation in three cases, severe nodular appearance in four cases and
      no pathology in four cases. All of the cases except patients with intestinal
      lymphangiectasia were controlled by the appropriate treatment given for the
      underlying disease. The cases with CMV infection were treated with only
      supportive treatment and gancyclovir therapy was not needed. CONCLUSION: When
      proteinuria is not detected in well-appearing children admitted with oedema, PLE
      must be considered.

PMID- 24564038
TI  - Predicting 24-hour urinary protein excretion in Afro-Caribbean Barbadians by
      comparing urine protein excretion over different durations versus spot
      collection.
AB  - AIM: The gold standard for the determination of proteinuria, an independent risk
      factor for cardiovascular and renal disease, is the measurement of protein in a
      24-hour urine collection. However this method has been shown to be unreliable
      mainly due to poor compliance of sampling by patients. This study investigates
      other appropriate means of predicting 24-hour urinary protein excretion in a
      sample of Afro-Caribbeans in Barbados by assessing the correlation of actual and
      estimated urinary protein excretion between a 24-hour urine collection sample, 12
      hour (AM and PM) and spot (AM and PM) urine collections. SUBJECTS AND METHOD: A
      convenient sample of 30 healthy participants of Afro-Caribbean origin between the
      ages of21 and 55 years was recruited for the study The 24-hour urine samples and
      anthropometric data were collected as documented in the study s standard clinical
      procedure. A 24-hour urine sample was collected as two separate 12-hour AM and PM
      samples. In addition, two spot samples (AM and PM) were taken during each 12-hour
      sample collection period. Analysis of the urinary protein and creatinine was done
      with a Roche/Hitachi Modular System (Roche Diagnostics, IN, USA). SPSS version 19
      was used to analyse the data to make inferences. RESULTS: Thirty Afro-Caribbean
      persons participated in the study: 16 females and 14 males. The average age and
      body mass index (BMI) were 38 +/- 17 years and 25.32+/- 5.98 kg/m2, respectively.
      The Spearman Rho 's correlation was used to interpret associations of the urinary
      parameters in 24-hour collected sample and the other samples. The strongest
      correlation of the protein:creatinine ratio in the 24-hour collected sample to
      the other samples was observed with the 12-hour AM sample (r = + 0.743, p <
      O.01)followed by the 12-hour PM sample (r = +0.672, p < 0.01). On analysing
      gender, the more significant correlations found were among the males for the 12
      hour timed samples with r = +0.945, p < 0.01 and r = +0.736, p < 0.01 for the AM
      and PM samples, respectively. There were very strong correlations between the 24
      hour urinary protein excretion and the estimated 24-hour protein excretion from
      the 12-hour AM and PM samples (r = +0.846, p < 0.01 and r = +0.637, p < 0.01,
      respectively). Both males and females had the strongest correlation for the
      estimation of 24-hour protein excretion in the 12-hour AM sample (r = +0.795, p <
      0.01 and r = +0.965, p < 0.01, respectively). CONCLUSION: The use ofa 12-hour
      timed sample, specifically the morning sample, may be a more convenient way to
      assess proteinuria in the Afro-Caribbean population. This method allows for a
      quicker assessment of proteinuria which not only allows earlier diagnosis of
      renal disease but may also reduce the clinical cost of the disease s management.

PMID- 24564039
TI  - Vitamin D deficiency in risk groups living in tropical Curacao.
AB  - OBJECTIVE: Curacao (12 degrees 10ON, 69 degrees OW) is characterized by whole
      year abundant sunshine (8-10 hours/day). We challenged the automatic assumption
      that people living in tropical countries do not have a high risk of vitamin D
      deficiency, and investigated the vitamin D status in a tropical environment.
      METHODS: For this, we selected fifty-two elderly people with little or no
      exposure to direct sunlight [median 84 (60-96) years; 34females, 18 males] and
      who were cared for by community nurses or lived in retirement or nursing homes.
      Furthermore, six rehabilitating orthopaedic patients [median 72 (38-90) years;
      one female, five males] were included. Serum 25(OH)D, calcium, phosphate,
      parathyroid hormone (PTH) and creatinine were measured. Those exhibiting elevated
      creatinine, PTH or both had their 1,25-dihydroxyvitamin D [1,25(OH)2D] examined.
      RESULTS: Serum levels of 25(OH)D below 25, 50 and 75 nmol/L were detected in,
      respectively, seven (12%), 22 (38%) and 48 (83%) ofthe fifty-eight persons. Four
      persons had combined high creatinine and PTH, and low 1,25(OH)2D, which was not
      known by their caregivers. CONCLUSION: Abundant sunshine outdoors is no guarantee
      for vitamin D sufficiency. More attention is needed for vitamin D deficiency in
      risk groups living in tropical areas and elderly persons with poor kidney
      function.

PMID- 24564040
TI  - Vitamin D deficiency rickets in infants presenting with hypocalcaemic
      convulsions.
AB  - AIM: Hypocalcaemia evaluation of the clinical, biochemical and
      radiologicalfeatures of 91 infants with rickets who presented as hypocalcaemic
      convulsions. SUBJECTS AND METHODS: Ninety-one hypocalcaemic infants who were
      brought to hospital with convulsion and diag-nosed with rickets related to
      vitamin D deficiency according to their clinical, biochemical and radio
      logicalfeatures were retrospectively reviewed. RESULTS: Mean values of the
      laboratory data were as follows: calcium 5.55 +/- 0.79 mg/dL, phosphorus 4.77 +/-
      1.66 mg/dL, alkaline phosphatase 1525.5 +/- 925.4 U/L and parathormone 256.8 +/-
      158.3 pg/mL. Serum 25-OH vitamin D levels were below normal (< 20 ng/mL) in 37
      infants. CONCLUSION: Vitamin D deficiency should be considered in infants
      presenting with hypocalcaemia. To avoid complications such as convulsions,
      clinicians should give vitamin D supplementation to such infants.

PMID- 24564041
TI  - Evaluation of the efficacy of pulsed electromagnetic therapy in the treatment of
      back pain: a randomized controlled trial in a tertiary hospital in Nigeria.
AB  - Musculoskeletal system disorders (MSDs) are amongst the most commonly encountered
      problems in orthopaedics and physiotherapy practice all over the world and back
      pain is amongst the most prevalent of musculoskeletal presentations encountered
      in clinical practice. The attendant deformities, huge economic loss among many
      other sequelae on the affected individuals have always informed the search for
      cost-effective treatment modalities that are non-invasive and are devoid of or at
      least have minimal side effects. This randomized controlled trial was conducted
      to assess the therapeutic efficacy of the use of a non-pharmacological device
      [pulsed electromagnetic field (PEMF)] modality in the treatment of back pain. A
      total of 16 patients (mean age: 42.82 +/- 8.63 years) with back pain without
      radiculopathy who met the inclusion criteria were purposively enrolled in the
      study. Patients were randomly assigned into two groups. Group A had eight
      patients treated with PEMF plus medications (analgesics, nonsteroidal anti
      inflammatory - diclofenac sodium) while the eight patients in group B were
      treated with only standard medications. The PEMF device was applied in group A
      four times a day for the period the patients were admitted (maximum of nine
      days). Measured outcome parameters were reduction in pain as assessed with
      numeric pain rating scale (NPRS) and improvement in functional ability status as
      assessed with functional activity scale (FAS). Obtained data were analysed with
      paired and independent t-test to test the significant efficacy of the treatment
      outcomes in the two groups. There was a statistically significant faster pain
      relief and resumption of active functions in patients treated with PEMF plus
      analgesic compared with the rates exhibited by patients treated with standard
      analgesics alone. These results suggest that PEMF therapy is beneficial in
      reducing pain and disability in patients with back pain and should be made part
      of holistic cape for back pain. Further studies using PEMF on larger patient
      populations are advocated to further confirm the efficacy of PEMF therapy in back
      pain management.

PMID- 24564042
TI  - Comparative proteomic analysis of the nucleus accumbens during extinction and
      reinstatement of morphine dependence.
AB  - BACKGROUND: The aim of this study was to detect differentially expressed proteins
      in the nucleus accumbens between the states of extinction and reinstatement
      ofmorphine addiction. Numerous studies on the neurobiological mechanisms
      concerning drug craving and relapse have been reported to date, but data on their
      relationship with the underlying key molecular mechanisms involved remain
      limited. METHODS: In this study, 40 male Sprague-Dawley rats were equally
      randomized into a saline group and a morphine group. Both groups received drug
      self-administration training, after which extinction models were established
      naturally. The groups were further divided into two subgroups for extinction and
      reinstatement tests. Cerebral nucleus accumbens masses were measured for total
      protein extraction. Two-dimensional electrophoresis was performed to determine
      differential protein spots. These differential proteins were then enzymolysed and
      identified using mass spectrography. RESULTS: The proteins were classified as
      fatty acid-binding protein, serine/threonine protein phosphatase 2A catalytic
      subunit beta isoform, serine/threonine protein phosphatase 2A catalytic subunit
      alpha isoform, serine/threonine protein phosphatase 2A regulatory subunit B2
      subunit gamma or heat shock protein 90 co-chaperone CDC37. CONCLUSION:
      Significant changes in five proteins were detected between extinction and
      reinstatement. These proteins are correlated with phosphorylation and the
      tricarboxylic acid cycle.

PMID- 24564043
TI  - Diabetic foot complications among patients attending a specialist diabetes clinic
      in Jamaica: prevalence and associated factors.
AB  - OBJECTIVES: To estimate the prevalence of diabetic foot complications among
      patients at a specialist diabetes clinic in Jamaica and identify factors
      associated with foot complications. METHODS: A stratified random sample of 188
      patients were interviewed and examined between 2009 and 2010. Trained nurses
      obtained demographic and clinical data, measured anthropometrics and
      performedfoot examinations including inspection for amputations, ulcers or
      infection and assessment of pain, vibration and pressure perception. RESULTS:
      Participants included 143 women and 45 men (mean age 56years; mean diabetes
      duration 16 years). The prevalence of amputations was 8.5% (95% CI 4.5, 12.5%)
      and was higher among men (22.2%) compared to women (4.2%, p < 0.05). Prevalence
      of current ulcers and current foot infections was 4.3% and 3.7%, respectively.
      Overall, 12% ofpatients had at least one of these foot complications. Foot
      complications were more prevalent among men, patients with high blood pressure
      (BP > or = 130/80 mmHg) or peripheral neuropathy In multivariable logistic
      regression models, factors associated with foot complications were: neuropathy
      (OR 9.3 [95% CI 2.8, 30.3]), high BP (OR 7.9 [1.3, 49.7]) and diabetes duration
      (OR 1.32 [1.02, 1.72]). CONCLUSION: Approximately one of every eight patients in
      this specialist clinic had a major foot complication. Associated factors were
      neuropathy, high blood pressure and longer duration of diabetes.

PMID- 24564044
TI  - Severe sepsis in the emergency department - an observational cohort study from
      the university hospital of the West Indies.
AB  - OBJECTIVE: To describe the incidence, treatment and outcomes of patients with
      severe sepsis and septic shock in a setting where early goal directed therapy
      (EGDT) is not routinely performed. METHOD: An observational study of all adult
      patients admitted from the emergency department (ED) of the University Hospital
      of the West Indies (UHWI) with a diagnosis of severe sepsis and septic shock from
      July 5, 2007 to September 1, 2008 was conducted. Baseline parameters, treatment
      patterns and in-hospital outcomes were evaluated. RESULTS: A total of 58 011
      patients were seen and 762 (1.3%) had sepsis, 117 (15.4%) of whom were classified
      as severe sepsis or septic shock. Mean (SD) age was 59.2 (23.3) years and 49%
      were female. Medical history included hypertension (29%), diabetes mellitus
      (26%), stroke (8%), heart failure (6%) and HIV (6%). The most common sources of
      sepsis were pneumonia (67%) and urinary tract infection (46%). Median,
      interquartile range (IQR) time from triage to antibiotic administration was 126
      (88, 220) minutes and antibiotics were given to 65.7% within three hours.
      Overall, organisms were sensitive to empirical antibiotics in 69%. Median (IQR)
      lactate was 5.3 (4.5, 7.5) mmol/L. Most patients (95%) were admitted to the ward;
      1% went to the intensive care unit (ICU) and 2% died in the ED. Mean (SD) length
      of hospital stay was 9.5 (10.3) days. In-hospital mortality was 25% and survival
      correlated inversely with age (rpb = -0.25; p = 0.006). CONCLUSION: Despite a
      lack of EGDT, sepsis treatment patterns were consistent with "best-practice" and
      mortality was lower than international comparators.

PMID- 24564045
TI  - Evaluation of hbetaD-1 and hbetaD-2 levels in saliva of patients with oral
      mucosal diseases.
AB  - OBJECTIVE: This study aimed to determine a possible correlation between oral
      mucosal disease and salivary concentrations of the antimicrobial peptides human
      beta-defensin-1 (hbetaD-1) and human beta-defensin-2 (hbetaD-2). METHOD: The
      present work focussed on the establishment of a reversed phase-high performance
      liquid chromatography (RP-HPLC) procedure to quantify human beta-defensins
      (hbetaD-1 and hbetaD-2) in saliva samples of patients with oral diseases such as
      lichen planus (n = 10), Behcet (n = 10) and recurrent apthous stomatitis (n =
      10). RESULTS: Linear calibration range for hbetaD-1 and hbetaD-2 defensins was
      1.67-200 microg mL-1 and 3.13 -100 PG mL-1 with R2 values of 0.9998 and 0.996,
      correspondingly. The concentration of beta-defensins in saliva was determined by
      comparing the peak areas of eluted hbetaD-1 and hbetaD-2 with that of their
      standards. The variation of the amount of beta-defensins was evaluated by
      comparisons of the results obtained from the patients with oral mucosal diseases
      before and after treatments and the control subjects. The limit of detection
      (LOD) and limit of quantification (LOQ) were found to be 1.62 microg mL-Sand 5.39
      microg mL-1 for hbetaD-1 and 0.94 mig mL-1 and 3.13 microg mL-1 for hbetalD-2,
      respectively. CONCLUSION: The salivary beta-defensin concentration was
      significantly higher in patients with oral mucosal diseases than in healthy
      volunteers; furthermore, in patients with oral mucosal diseases, the
      concentration was significantly higher before treatment than after treatment.

PMID- 24564046
TI  - A changes in hyoid bone position after orthodontic treatment of patients with
      mandibular deviation.
AB  - OBJECTIVES: The aim of this study was to observe the influence of orthodontic
      treatment on the hyoid position of patients with different vertical skeletal
      craniofacial patterns of mandibular deviations. METHODS: A total of 60 patients
      with mandibular deviations, including 30 males and 30 females with a mean age of
      15.4 years, were recruited. They were equally divided into average angle, high
      angle, and low angle groups, with a 1:1 gender ratio. Their hyoid position was
      measured before and after orthodontic treatment. The data were analysed using
      paired t-tests and analysis of variance (ANOVA). RESULTS: After treatment, the
      hyoid body in the high angle group presented significant forward and upward
      movements (p = 0.012 and p = 0.005). The hyoid body in the low angle group
      exhibited significant forward movement (p = 0.048) and a significant increase in
      the hyoid inclination (p = 0.00). In the average angle group, the hyoid body
      significantly moved downward (p = 0.031) and the thyrohyoid moved upward (p =
      0.046). The ANOVA showed that orthodontic treatment significantly influenced the
      vertical position and inclination degree of the hyoid (F = 6.37, p = 0.003; F =
      6.204, p = 0.004; and F = 3.393, p = 0.025). The average angle group displayed
      significant differences in these indices compared with the high angle and low
      angle groups. Orthodontic treatment significantly influenced the mandibular plane
      angle in the high angle group (p = 0.012). CONCLUSION: Orthodontic treatment
      influences the hyoid position of patients with different vertical skeletal
      craniofacial patterns of mandibular deviations by varying degrees.

PMID- 24564047
TI  - Cuba: healthcare and the revolution.
AB  - This paper depicts Cuba as a relic of the Cold War Its coverage of healthcare
      demonstrates steadfastness and success in surmounting hurdles of complacency and
      disregard to socialized medicine - an extension of Soviet patronage and third
      world alliances. The literature relays a mission of inclusivity underpinned by
      political ideology and a conviction to humanity. With the aid ofendorsements, it
      speaks to contrasts and critiques in service and results by reflecting on the
      delivery offree healthcare for all Cuban citizens and its impression on the
      eradication of numerous diseases, reduced mortality rate and increased life
      expectancy. Punished by the longest trade embargo in modern history, the regime
      is in possession of limited resources to expedite remedy to its subjects. Such,
      much to the dislike of the authorities, elevates elements of distinction in
      association with the dispensation of service and drugs demonstrated by an
      evolving two-tier system for the disenfranchised and privileged clientele while
      simultaneously impacting the maintenance of facilities and equipment.
      Consequently, it recognizes harsh ramifications attributed to compliance with
      ideology and subtle adjustments to withstand external exertion. The Cuban replica
      is currently a tale of sorts awaiting a comprehensible definition for future
      generations.

PMID- 24564048
TI  - Medical tourism in the Caribbean region: a call to consider environmental health
      equity.
AB  - Medical tourism, which is the intentional travel by private-paying patients
      across international borders for medical treatment, is a sector that has been
      targeted for growth in many Caribbean countries. The international development of
      this industry has raised a core set of proposed health equity benefits and
      drawbacks for host countries. These benefits centre on the potential investment
      in health infrastructure and opportunities for health labour force development
      while drawbacks focus on the potential for reduced access to healthcare for
      locals and inefficient use of limited public resources to support the growth of
      the medical tourism industry. The development of the medical tourism sector in
      Caribbean countries raises additional health equity questions that have received
      little attention in existing international debates, specifically in regard to
      environmental health equity. In this viewpoint, we introduce questions of
      environmental health equity that clearly emerge in relation to the developing
      Caribbean medical tourism sector These questions acknowledge that the growth of
      this sector will have impacts on the social and physical environments, resources,
      and waste management infrastructure in countries. We contend that in addition to
      addressing the wider health equity concerns that have been consistently raised in
      existing debates surrounding the growth of medical tourism, planning for growth
      in this sector in the Caribbean must take environmental health equity into
      account in order to ensure that local populations, environments, and ecosystems
      are not harmed by facilities catering to international patients.

PMID- 24564049
TI  - Klippel-Trenaunay syndrome.
AB  - Klippel-Trenaunay syndrome (KTS) is a rare congenital, vascular disorder
      affecting one or more limbs. The syndrome is characterized by capillary
      malformations, soft tissue or bony hypertrophy and varicose veins or venous
      malformations. We present a case of this disorder in a twelve-year old boy who
      had an enlarged right lower limb with varicosities. Investigations revealed
      extensive superficial and deep venous varices, with dilatation of the right
      common iliac and external iliac veins. Klippel-Trenaunay syndrome should be
      suspected in a child presenting with capillary haemangioma and an enlarged limb.

PMID- 24564050
TI  - Pyosalpinx and hydrosalpinx in virginal adolescents: report of two cases.
AB  - Pyosalpinx and hydrosalpinx are conditions mainly seen in adult women, but also
      among sexually active adolescents and can bring added hazard to fertility.
      However these conditions are very rare in childhood, as well as in adolescent
      girls who are not sexually active. We are presenting two rare cases of young
      girls in early puberty with hydrosalpinx and pyosalpinx. Both girls had a history
      of abdomino-pelvic surgery in childhood for congenital bowel anomalies and fecal
      incontinence. Such cases are good reminders that girls with known abdomino-pelvic
      anomalies and surgical procedures in childhood need long term follow-up, in
      particular when entering puberty and maturation. The two cases show how fallopian
      tubes can be indirectly affected and present in adolescence with serious problems
      needing surgical procedures and potentially threatening future reproductive
      system performances.

PMID- 24564051
TI  - Two women with cerebral venous thrombosis: oral contraceptives?
AB  - Two cases of cerebral venous thrombosis are reported. Patients were apparently
      healthy 39 and 28-year old females with non-specific presenting features. Image
      findings were characteristic of cerebral sinus thrombosis. The younger patient
      received progesterone to treat placental abruption eight years previously; she
      had cerebral venous thrombosis while using oral contraception. Both patients had
      used contraceptive pills for a long time. Oral hormonal contraceptives may
      increase the risk of vascular events, even in people without personal or family
      history of venous thrombosis. Modern imaging methods have contributed to early
      diagnosis, but the possibility of under diagnosis still persists. This report
      aims to increase the awareness of health-workers about cerebral venous thrombosis
      in women, an entity often misdiagnosed, under diagnosed and under-reported.

PMID- 24564052
TI  - Thymoma associated with myasthenia gravis and Sjogren syndrome.
AB  - Thymoma is the most common neoplasm of the anterior mediastinum but thymoma with
      Sjogren syndrome (SS) is rare. Sjogren syndrome is a systemic autoimmune
      inflammatory disorder. It is characterized by lymphocyte-mediated destruction of
      exocrine glands, which leads to absent glandular secretion. Here, we present the
      case of a 63-year-old man with thymoma and concurrent myasthenia gravis and SS,
      who achieved remission after thymectomy.

PMID- 24564053
TI  - Cystic echinococcosis: a disease mimicking cancer in a non-endemic country report
      of two cases.
AB  - Echinococcosis is a parasitic disease that involves dogs as definitive host and
      sheep as intermediate host. Humans become infected incidentally through fecal
      oral contact, particularly in the course of playful and close contact with an
      infected dog. Mexico is considered a region that is virtually free of cystic
      echinoccocosis. This manuscript describes two cases that were referred to a
      tertiary-care oncology hospital with a diagnosis of cancer. In one case, the
      presumptive diagnosis was liver cancer because abdominal ultrasonography revealed
      a low-density mass in the right hepatic lobe. Drainage was performed and
      cytologic examination of the fluid showed multiple Echinococcus cyst as well as
      prostoscolex. The case was resolved with percutaneous drainage and administration
      of albendazole for two months. In the second case, the patient was referred with
      a diagnosis of disseminated cervical cancer A cyst was identified in the upper
      right lung lobe; a diagnostic puncture was performed showing an Echinococcus
      cyst. This resolved solely with two months of albendazole administration.

PMID- 24564055
TI  - Truncus arteriosus: surviving at 46 years without intervention.
AB  - The median survival of patients with truncus arteriosus is five weeks of age with
      rare cases reaching adulthood. The longest reported survivor with balanced
      ventricles, as the index case has, is 38 years of age. The index case is a 46
      year old male with Type 3 truncus arteriosus. His case has never been documented
      in the English Literature as far as the author is aware.

PMID- 24564057
TI  - Tuberculosis in HIV: making good with what we have.

PMID- 24564054
TI  - Salmonella enterica arthritis in a patient with rheumatoid arthritis receiving
      anti-tumour necrosis factor therapy.
AB  - Anti-tumour necrosis factor (TNF) monoclonal antibodies have become an invaluable
      treatment against chronic inflammatory diseases such as rheumatoid arthritis
      (RA). However, due to increased risk of opportunistic infections, patients
      receiving anti-TNF therapy should be closely monitored for serious infections.
      Here, we describe a case of acute Salmonella_enteritidis infection of a joint
      arthroplasty that previously was functioning well, in a patient receiving
      infliximab treatment for RA. After prolonged antimicrobial chemotherapy and
      interrupted infliximab treatment, reimplantation of a new prosthesis was
      successfully performed two years after Salmonella septic arthritis. Therefore,
      because of the possibility of extraintestinal salmonellosis, screening for fecal
      colonization could be advisable in patients undergoing anti-TNF treatment.
      Moreover we emphasize the importance of appropriate counselling of these patients
      concerning food hygiene.

PMID- 24564056
TI  - Anomalous origin of left coronary artery with left anterior descending artery
      connected to left pulmonary artery from single right coronary artery.
AB  - Single right coronary artery, so defined because all three coronary arteries
      arise from the single right aortic sinus of Valsalva, is an extremely rare entity
      occurring in less than 0.03% of the population. This case identifies a single
      coronary artery with the left anterior descending coronary artery distally
      connected to the left pulmonary artery with development of pulmonary
      hypertension. To the author's knowledge, this has never been documented in the
      English literature.

PMID- 24564058
TI  - Assessment of the ability of the triglyceride to high density lipoprotein
      cholesterol ratio to discriminate insulin resistance among Caribbean-born black
      persons with and without Hispanic ethnicity.
AB  - OBJECTIVE: The objective of this research was to determine if the triglyceride
      (TG) to high density lipoprotein (HDL) cholesterol (TG/HDL) ratio has similar
      utility for discriminating insulin resistance in Caribbean-born black persons
      with and without Hispanic ethnicity. METHODS: Serum lipids, glucose and insulin
      were determined and compared for 144 Hispanic blacks and 655 non-Hispanic blacks
      living in the US Virgin Islands. Area under the receiver operating
      characteristics (AUROC) curve statistics were used to evaluate the ability of the
      TG/HDL ratio to discriminate insulin resistance in the two ethnic groups.
      RESULTS: Hispanic blacks had significantly higher levels of triglycerides and
      insulin resistance and a lower level of HDL cholesterol than non-Hispanic blacks.
      The AUROC curve for the ability of the TG/HDL to discriminate insulin resistance
      was 0.71 (95% CI = 0.62, 0.79) for Hispanic blacks and 0.64 (95% CI = 0.59, 0.69)
      for non-Hispanic blacks. CONCLUSIONS: Among Caribbean-born black persons living
      in the US Virgin Islands, the TG/HDL ratio is a useful screening measure for
      discriminating insulin resistance in those with Hispanic ethnicity but not in
      those without Hispanic ethnicity.

PMID- 24564059
TI  - A prediction equation for the estimation of cardiorespiratory fitness using an
      elliptical motion trainer.
AB  - OBJECTIVE: In the United States of America, 6.2 million individuals are using
      elliptical motion trainers in fitness centres. However, graded exercise test
      protocols to estimate peak oxygen consumption (VO(2peak)) using elliptical motion
      trainers have not been developed for the general population. METHODS: Fifty-nine
      subjects (mean age: 23.5 +/- 4.1 years) were randomly divided into a validation
      (VAL: n = 39) or cross-validation (XVAL: n = 20) group. Peak oxygen consumption
      (ml x kg(-1) x min(-1)) was measured via indirect calorimetry on an elliptical
      motion trainer for both groups. Subjects exercised at 150 strides x min(-1)
      against a resistance of four and a crossramp of 8%. The resistance was increased
      every two minutes by two units until exhaustion. For the VAL group, a stepwise
      regression analysis was used to predict VO(2peak) from resistance, maximal heart
      rate (HR(max)), body mass index (BMI), height and gender (female = 0, male = 1).
      RESULTS: The prediction equation derived from this study was VO(2peak) (ml x kg(
      1) x min(-1)) = 187.39403 + 12.97271 (gender) - 1.45311 (height) - 1.21604 (BMI) 
      0.19613 (HR(max)) + 1.57093 (resistance) (R2 = 0.76, SEE = 4.47, p < 0.05).
      Using this equation, the predicted VO(2peak) of the XVAL group was 45.18 +/- 6.42
      ml x kg(-1) x min(-1), while the measured VO(2peak) was 43.55 +/- 6.23 ml x kg(
      1) x min(-1) CONCLUSION: No significant difference was found between the measured
      and predicted VO(2peak) in the XVAL group. Therefore, it appears this protocol
      and equation will allow individuals to accurately estimate their VO(2peak)
      without using direct calorimetry. However future studies should investigate the
      validity of this protocol with diverse populations.

PMID- 24564060
TI  - Injuries in elite Jamaican netballers.
AB  - OBJECTIVES: The purpose of this study is to identify the nature, spectrum and
      frequency of injuries among national netballers in Jamaica. METHODS: A
      retrospective study utilizing a questionnaire was used to gather the necessary
      information among netball players over a five-year period spanning two world
      cups. A 31-item questionnaire on player's profile, protective equipment, site of
      injury and associated factors of injury was completed by a study population
      recruited from players who had represented Jamaica at the senior level, under 21
      or under 16 age groups between 2003 and 2007. Statistical analysis was done using
      the SPSS version 12. RESULTS: Most of the injuries were confined to the ankle and
      knee, with the playing surface and poor landing technique the main reasons for
      the injuries. CONCLUSIONS: There are wide variations in training, players'
      fitness, levels of coaching and the standards of playing courts, all of which
      might have contributed to players' injuries.

PMID- 24564062
TI  - Child abuse: a common problem in Curacao?
AB  - OBJECTIVE: To assess the prevalence of child abuse among high school students in
      Curacao. METHODS: A questionnaire survey among high school students up to 17
      years of age was conducted. The questionnaire was based on existing literature
      and validated questionnaires. The questionnaire used was analysed and adapted to
      the situation in Curacao by a panel of experts on child abuse. The primary
      objective was to gain insight into the incidence, prevalence and various forms of
      child abuse among students in Curacao. Five forms of child abuse are
      distinguished in the literature: physical abuse, emotional abuse, sexual abuse,
      neglect and exploitation. Furthermore, the degree of confidence of the students
      in general practitioners (GPs) as care providers in the field of child abuse was
      explored. RESULTS: Questionnaires from 545 of the 628 respondents were included.
      In total, 43% of the respondents had ever-experienced an event which could be
      defined as (a form of) child abuse. More than one-third of the respondents
      reporting child abuse ever had an experience that could be interpreted as
      physical abuse. More than 15% of the respondents reporting child abuse had
      experienced sexual abuse. Girls experienced significantly more sexual abuse than
      boys. Emotional abuse in the last year was experienced by 3% of the respondents.
      One per cent of the respondents ever-experienced neglect. According to most
      respondents, GPs were not seen as care providers in cases of child abuse; they
      believed that GPs were mainly to be consulted for illnesses or physical symptoms
      and not for forms of child abuse. CONCLUSION: The prevalence of ever-having
      experienced a form of child abuse is estimated at 431 per 1000 students. Child
      abuse, particularly physical abuse, is common in Curacao, and is probably
      comparable to other surrounding countries. General practitioners were not seen as
      care providers in identifying and reporting cases of child abuse according to
      most respondents.

PMID- 24564061
TI  - Detection of drug resistant Mycobacterium tuberculosis among patients with and
      without HIV infection in a rural setting.
AB  - OBJECTIVE: To analyse the sensitivity of Mycobacterium tuberculosis by nitrate
      reductase assay (NRA) and the Hain molecular line probe assay (LPA) in sputa of
      tuberculosis (TB)/HIV co-infected patients in Guyana. DESIGN: Sputum samples were
      collected from known TB patients at Georgetown Chest Clinic and were analysed at
      the Reference Laboratory, Guyana, over the period April 2010 to April 2011.
      RESULTS: Both methods recorded greater sensitivity for rifampin (RIF) than of
      isoniazid (INH). Both methods detected four RIF resistant, two INH resistant and
      two multi-drug resistant (MDR) strains and they had greater negative agreement
      indices than positive agreement indices. CONCLUSION: It was established that the
      sensitivity of Mycobacterium tuberculosis by the NRA and Hain LPA in TB/HIV co
      infected patients has acceptable correlation and that HIV infection does not
      affect drug susceptibility testing.

PMID- 24564063
TI  - Effect of clopidogrel with or without omeprazole in patients with carotid artery
      stenting.
AB  - BACKGROUND: Recent concerns have been raised about the potential for proton pump
      inhibitors (PPIs) to blunt the efficacy of clopidogrel. We observed the effect of
      clopidogrel plus aspirin with or without omeprazole in patients with carotid
      stenoses after they received placement of carotid stents. METHODS: Sixty-four
      consecutive patients treated with percutaneous carotid artery stenting (CAS)
      comprised the sample. All enrolled patients underwent the C13 urea breath test
      (C13 UBT) before CAS. Patients with Helicobacter pylori infection and a history
      of peptic ulcer were assigned dual antiplatelet combination with omeprazole.
      Others received dual antiplatelet without omeprazole. Transcranial Doppler and
      ultrasonography were performed to assess the middle cerebral artery and carotid
      artery in follow-up at three months and six months. RESULTS: Eight patients had
      gastrointestinal bleeding; the event rate was 22.6% without omeprazole and 3.8%
      with omeprazole. The rate of gastrointestinal bleeding was reduced with
      omeprazole as compared without omeprazole (p = 0.026, p < 0.05). The two groups
      did not differ significantly in the rate of in-stent restenosis and thrombus
      through transcranial Doppler and ultrasonography. CONCLUSION: Among patients
      receiving dual antiplatelet therapy, prophylactic use of omeprazole reduced the
      rate of upper gastrointestinal bleeding. There was no apparent interaction
      between clopidogrel and omeprazole in patients with carotid artery stenting.

PMID- 24564064
TI  - What is the best clothing to prevent heat and cold stress? Experiences with
      thermal manikin.
AB  - The present study summarizes the current knowledge of the heat and cold stress
      which might significantly affect military activities and might also occur among
      travellers who are not well adapted to weather variations during their journey.
      The selection of the best clothing is a very important factor in preserving
      thermal comfort. Our experiences with thermal manikin are also represented in
      this paper.

PMID- 24564065
TI  - Comparative study of the osteoblastic activity of two implant systems (Endopore
      versus Entegra) utilizing single photon emission computed tomography (SPECT):
      experimental study in pigs model.
AB  - Implantology has been an important component of dental management for over forty
      years, and during that period, many configurations of implant materials and
      methods have been developed. As empirical and clinical research yield new implant
      materials, there has been need to test and compare these materials to provide the
      most cost-effective and efficient implants. Evaluation of efficiency of implants
      has relied heavily on histological and radiological methods, but these one
      dimensional measurement methods fail to evaluate the osteoblastic activity and
      osseointegration properties of putative implants. In this report, we describe the
      use of a quantitative single photon emission computed tomography (SPECT) as a
      tool for comparing the osseointegrating capabilities of two types of implants.

PMID- 24564066
TI  - Syndromic association of pyloric atresia and epidermolysis bullosa (Carmi
      syndrome)--a case report.
AB  - Epidermolysis bullosa (EB) is an inherited, autosomal recessive, bullous disease,
      characterized by blisters followed with skin and mucosal erosions. We present a
      case of a male infant with pyloric atresia associated with junctional EB (Carmi
      syndrome). The patient underwent urgent laparotomy after prompt stabilization.
      Postoperative course was uneventful. Nine months later the patient died in the
      paediatric intensive care unit from respiratory distress syndrome. Prognosis is
      usually very poor. Death usually occurs during the first year of life, as a
      result of septic complications.

PMID- 24564067
TI  - Boerhaave's syndrome: a differential diagnosis of acute chest pain following a
      vomiting illness.
AB  - Spontaneous oesophageal rupture (Boerhaave's syndrome) is extremely rare in
      children. Presentation is usually in middle aged men as a result of vomiting
      following heavy food or alcohol consumption. We describe an unusual case of a 12
      year old boy without significant past medical history presenting with acute chest
      pain following gastroenteritis.

PMID- 24564068
TI  - Nasal lipoma with associated abnormalities of the corpus callosum.

PMID- 24564070
TI  - Laparoscopic ovarian ligament plication in pregnancy.
AB  - This 32-year old patient presented at seven weeks gestation with severe left
      sided lower abdominal pain. This was against the background of a previous history
      of left salpingectomy from a ruptured ectopic gestation seven years previously.
      Transvaginal sonographic evaluation revealed a viable seven week intrauterine
      embryo, a 2 cm left corpus luteum cyst and Doppler studies revealed reduced
      internal flow. This led the way for a conservative approach via laparoscopy of
      untwisting the pedicle to restore blood flow In this case, the ovarian ligament
      was shorted using 1/0 vicryl and the pregnancy went to term.

PMID- 24564069
TI  - Terminal ileum duplication: an unusual case of small bowel obstruction.
AB  - Duplications of the alimentary tract are uncommon congenital anomalies that
      usually present during infancy and early childhood. The case of an adolescent
      presenting with small bowel obstruction secondary to a duplication cyst is
      presented and the challenges in the management described.

PMID- 24564071
TI  - Gastroesophageal reflux and reflux oesophageal strictures in children with
      Cornelia de Lange syndrome.

PMID- 24564072
TI  - Why do patients with non-life threatening conditions bypass their local health
      centres? A cross-sectional survey at accident and emergency departments in
      Trinidad.

PMID- 24564073
TI  - Mebendazole as an alternative in Giardia duodenalis infection.

PMID- 24564074
TI  - [Salvage therapy for castration-refractory prostate cancer resistant to
      docetaxel].
AB  - OBJECTIVES: To evaluate the treatment for castration-refractory prostate cancer
      (CRPC) resistant to docetaxel MATERIALS AND METHODS: Among 45 patients with CRPC
      treated with docetaxel (70-75 mg/m2) every 3 to 4 weeks at Hamamatsu University
      Hospital from January 2004 to July 2012, 19 patients underwent salvage
      treatments. We retrospectively analyzed the medical records of 14 patients except
      for 5 patients who were enrolled in clinical trials. RESULTS: The median age and
      serum prostate-specific antigen (PSA) level at starting salvage treatments was 71
      years (range 45 to 79) and 241.1 ng/mL (range 3.06 to 1,643.0), respectively. All
      patients maintained castration status. Salvage treatments include DTX (30 mg/m2)
      + cisplatin (CDDP) (70 mg/m2)/carboplatin (Area under the curve = 4), etoposide +
      CDDP, paclitaxel + CDDP, cyclophosphamide, S-l, tegaful-uracil. The reasons why
      14 patients moved to salvage treatments after DTX were progressive disease in 12
      patients and adverse events in 2. Eight patients had a PSA response, 3
      patients>50% and 5 patients<50%. Six patients had a PSA progression. The median
      overall survival was 10.4 months (range 4.1 to 27.3). All patients died of
      cancer, 13 patients with prostate cancer and one patient with lung
      adenocarcinoma. Most adverse events were mild. Transitory grade 3 leukopenia was
      observed in 2 patients, and grade 3 anemia in 2. No grade 4 toxicities were
      noted. CONCLUSIONS: All salvage treatments without grade 4 toxicities described
      in this study may be acceptable in the patients with CRPC progressing after
      docetaxel although the effect would be limited.

PMID- 24564075
TI  - [Role of transcatheter arterial embolization (TAE) for deep renal injury].
AB  - PURPOSE: We evaluated usefulness of transcatheter arterial embolization (TAE) for
      deep renal injury, and investigated whether there is any difference in outcomes
      for transcatheter arterial embolization (TAE) performed for deep renal injury in
      a large-sized hospital (university hospital) in comparison with a middle-sized
      hospital (local hospital). METHODS: We retrospectively reviewed the outcomes of
      42 patients with renal injury who were transported to the critical care center of
      Nippon Medical School (NMS) Hospital in Tokyo from April 2001 to April 2011 and
      33 patients of renal injury transported to the critical care center of Ohtawara
      Red Cross (ORC) Hospital in Tochigi prefecture from April 2001 to April 2009.
      Therefore, a total of 75 patients, which is the sum of the patients presenting to
      both the hospitals for renal injury were reevaluated according to the guidelines
      developed by the Japanese Association for the Surgery of Trauma (JAST) and
      published in 2008. RESULTS: Forty-two patients in NMS hospital included 6 women
      and 36 men who were 16 to 88 years old (mean 41.6), and they were divided into
      Type I (16), Type II (11), and Type III (15) and were treated with bedrest (30),
      TAE (7), or laparotomy (5). Five patients died, but no one succumbed solely due
      to the renal injury. On the other hand, 33 Patients in ORC Hospital included 8
      women and 25 men who were 16 to 87 years old (mean 46.6). They were divided into
      Type I (9). Type II (12), and Type III (12) and were treated with bedrest (24) or
      TAE (9). Eight patients died, but no one succumbed solely due to the renal
      injury. Sixteen patients were treated successfully with TAE in the 2 hospitals,
      and 15 of these 16 patients were divided into type III renal injury. Therefore,
      we believe that nephrectomy should be avoided in such patients because of the
      benefits offered by TAE. CONCLUSION: TAE was found to be useful for the treatment
      of type III renal injury in both institutions, irrespective of the size of a
      hospital.

PMID- 24564076
TI  - [Study of laparoendoscopic single-site surgery (LESS) for urachal remnants in our
      department].
AB  - OBJECTIVE: We examined laparoendoscopic single-site surgery (LESS) for urachal
      remnants and evaluated its usefulness and efficacy. PATIENTS AND METHODS: From
      August 2011 to July 2012, we underwent this surgery for 5 patients (3 males, 2
      females). The mean age was 30.8 (25-36) years old. A 2 cm incision was made
      around the umbilicus and Access Platform was placed. The entire urachal tissues
      were excised, and this 2 cm incison was reshaped as the umbilicus. RESULTS: The
      median operative time was 220 (156-460) minutes, and the median operative blood
      loss was 10 (10-70) ml. They had no operative complications, and were discharged
      6 (5-14) days after surgery. CONCLUSIONS: Our surgical procedures have very
      excellent cosmesis and advantages in particular for young because we reshape as
      the umbilicus the surgical wound. We think that this surgery can be performed
      safe and effectively for surgeons trained in the conventional laparoscopic
      procedures.

PMID- 24564077
TI  - [Case of heterochronous triple urogenital cancer (renal cell carcinoma, bladder
      cancer, prostatic cancer)].
AB  - We report a case of a 73-year-old male with heterochronous triple urogenital
      cancer. The patient was referred to our hospital because serum PSA was elevated
      (7.0 ng/ml) in 1998. Prostatic needle biopsy revealed prostatic cancer in the
      right lobe, and total prostatectomy was performed. The histopathological
      diagnosis was moderately differentiated adenocarcinoma (TlcNOMO). Non-muscle
      invasive bladder cancer (NMIBC) was detected during an examination for
      microhematuria in 2002. Transurethral resection of the bladder tumor (TURBT)
      procedure was performed, and the histopathological diagnosis was grade 2
      urothelial carcinoma (pTa). A right renal mass was detected incidentally on
      follow-up CT for bladder cancer in 2008. Renal enucleation was performed in 2009.
      The histopathological diagnosis was grade 2 clear cell renal cell carcinoma
      (pTlaNXMO). NMIBC was detected on follow-up urethrocystoscopy in 2011. The TURBT
      procedure was performed, and the histopathological diagnosis was grade 2
      urothelial carcinoma (pTa). On follow-up for urogenital cancer patients, it is
      important to investigate recurrence of the primary cancer and also heterochronous
      canceration of other urogenital organs.

PMID- 24564078
TI  - [Malignant fibrous histiocytoma/undifferentiated pleomorphic sarcoma of the
      penis: a case report].
AB  - We report the case of a malignant fibrous histiocytoma/undifferentiated
      pleomorphic sarcoma (MFH/UPS) of the penis in a 78-years-old-man who had
      undergone previous radical prostatectomy, external beam radiation therapy for
      prostatic adenocarcinoma. The mass was a 9-cm firm lesion at the base of the
      penis predominantly composed of malignant spindle cells arranged in sweeping
      fascicles and storiform pattern. The tumor cells stained for vimentin, beta
      smooth muscle actin, S-100, and were negative for keratin, desmin, Melan A, PSA.
      Despite total penectomy, he developed a local reccurence 4 months after surgery,
      and died from dissemination 6 months after surgery. This is the 8th case of
      penile MFH/UPS.

PMID- 24564079
TI  - [Two cases of epithelioid angiomyolipoma of the kidney].
AB  - Two cases of epithelioid angiomyolipoma of the kidney are reported. A 62-year-old
      female with incidental left renal tumor underwent laparoscopic leftpartial
      nephrectomy under a diagnosis of renal cell carcinoma. A pathological examination
      revealed epithelioid angiomyolipoma. The second case was that of a 35-year-old
      female with back pain. A laparoscopic right nephrectomy revealed epithelioid
      angiomyolipoma. This recently identified variant of angiomyolipoma is sometimes
      associated with aggressive clinical behavior including local recurrence and
      metastasis.

PMID- 24564080
TI  - [Nutcracker syndrome treated by endovascular stenting of the left renal vein].
AB  - We describe endovascular stenting of the left renal vein to treat Nutcracker
      syndrome accompanied by gross hematuria. A 26-year-old woman with a history of
      hematuria and left flank pain was admitted to another hospital in January 2009.
      She was referred to our hospital in August 2010 for further investigation and
      treatment for suspected Nutcracker syndrome based on her medical history and the
      recurrent gross hematuria. Computed tomography (CT) imaging revealed compression
      of the left renal vein between the aorta and the superior mesenteric artery and
      cystoscopy revealed bloody urine from the left ureteric orifice. Ureteroscopy
      revealed diffuse bleeding from the renal pelvic mucosa. The cytodiagnosis of
      urine was Class II. She developed left flank pain and further recurrent hematuria
      in July 2011 and sought active treatment by stenting at our hospital. After we
      obtained the approval of the Ethical Review Board in our institution, we treated
      by endovascular stenting of the left renal vein. The venous phase of selective
      renal angiography during the procedure revealed dilation of the mid-renal vein
      with delayed flow into the inferior vena cava and tortuous dilated collateral
      vessels. Two ELUMINEXX Vascular Stents (12 x 40 mm) were deployed at the stenotic
      site of the left renal vein via the right femoral vein. This strategy improved
      the stenosis and collateral vessels. No significant postoperative adverse events
      developed other than dull back pain that disappeared after a few days, and the
      patient was discharged on postoperative day 4. CT findings three months after the
      procedure confirmed resolution of the left renal vein compression. Six months
      post-procedure, the patient had no left flank pain or further hematuria.

PMID- 24564081
TI  - [Tumors of the skull base, extending into the orbit, paranasal sinuses, nasal
      cavity, pterygopalatine and infratemporal fossa].
AB  - The first of two papers focusing on surgery of skull base tumors invading orbit,
      sinonasal cavities, pterygopalatine and infratemporal fossae the authors
      described foundation and development of craniofacial oncology as a new discipline
      in skull base surgery, modern approaches to diagnostic evaluation of craniofacial
      mass lesions and basic principles of surgical management.

PMID- 24564082
TI  - [Radiosurgical irradiation of patients with cerebral AVM on the Gamma knife].
AB  - Arterio-venous malformation (AVM) of the brain are congenital malformations of
      cerebral vessels in the embryonic period. Standards in AVM treatment is currently
      applying the endovascular technique, microneurosurgical removal and stereotactic
      radiation. MATERIALS AND METHODS: In the period from 2005 to 2011, in 139
      patients with arteriovenous malformations of the brain were treated using "Gamma
      Knife". 89 (64%) of 139 patients suffered bleeding in anamnesis. Paroxysmal
      symptoms of varying severity dominated in the clinical picture of 35 (27%)
      patients. Previous microsurgical resection was performed in 10 patients. 28
      patients experienced a partial embolization of vascular malformations before
      radiosurgery. A boundary value radiation dose ranged from 18 to 28 Gy (mean dose
      20 Gy), day dose was in the range of 40-80% (average 50% isodose). Maximum dose
      ranged between 18-60 Gy (mean dose of 38 Gy.). RESULTS: Control angiography or
      spiral CT screening angiography was performed in all 85 patients who were treated
      with follow-up data for more than two years, showed that total obliteration
      occurred in 75% of cases. Frequency of symptomatic radiation reactions was less
      than 5%. After two years or more after treatment, complete obliteration was
      observed in 74% of patients. CONCLUSIONS: Higher frequency of AVM obliteration
      was seen with up to 2 cc. and the irradiation dose of at least 24 Gy.

PMID- 24564083
TI  - [fMRI study of the dominant hemisphere for language in patients with brain
      tumor].
AB  - THE AIM OF THE STUDY: Paper describes a study of language lateralization of
      patients with brain tumors, measured by preoperative functional magnetic
      resonance imaging (fMRI) and comparison results with tumor histology and profile
      of functional asymmetry. METHODS: During the study 21 patient underwent fMRI
      scan. 15 patients had a tumor in the left and 6 in the right hemisphere. Tumors
      were localized mainly in the frontal, temporal and fronto-temporal regions.
      Histological diagnosis in 8 cases was malignant Grade IV, in 13 cases--Grade I
      III. fMRI study was perfomed on scanner "Signa Exite" with a field strength of
      1.5 As speech test reciting the months of the year in reverse order was used.
      fMRI scan results were compared with the profile of functional asymmetry, which
      was received with the results of questionnaire Annette and dichotic listening
      test. RESULTS: Broca's area was found in 7 cases in the left hemisphere, 6 had a
      tumor Grade I-III. And one patient with glioblastoma had a tumor of the right
      hemisphere. Broca's area in the right hemisphere was found in 3 patients (2
      patients with left sided tumor, and one with right-sided tumor). One patient with
      left-sided tumor had mild motor aphasia. Bilateral activation in both hemispheres
      of the brain was observed in 6 patients. All of them had tumor Grade II-III of
      the left hemisphere. Signs of left-handedness were revealed only in half of these
      patients. Broca's area was not found in 4 cases. All of them had large malignant
      tumors Grade IV. One patient couldn't handle program of the research.
      CONCLUSIONS: Results of fMRI scans, questionnaire Annette and dichotic listening
      test frequently were not the same, which is significant. Bilateral activation in
      speech-loads may be a reflection of brain plasticity in cases of long-growing
      tumors. Thus it's important to consider the full range of clinical data in
      studying the problem of the dominant hemisphere for language.

PMID- 24564084
TI  - [Virtual clinical diagnosis support system of degenerative stenosis of the lumbar
      spinal canal].
AB  - The aim of the study was to develop a virtual clinical diagnostic support system
      of degenerative lumbar spinal stenosis on database of spine registry. MATERIALS
      AND METHODS: Choice of criteria's for diagnostic system was made on symptom
      analysis of 298 patients with lumbar spinal stenosis. Also was analysed a group
      of patient with disc herniation's for sensitivity and specify assessment of
      developed diagnostic support system. Represented clinical diagnostic support
      system allows identifying patients with degenerative lumbar spinal stenosis on
      stage of patient's primary visit. System sensitivity and specify are 90 and 71%
      respectively. RESULTS: "Online" mode of diagnostic system in structure of spine
      registry provides maximal availability for specialists, regardless of their
      locations. Development of tools "medicine 2.0" is the actual direction for
      carrying out further researches with which carrying out the centralized baea
      collection by means of specialized registers helps.

PMID- 24564085
TI  - [Flexible endoscopy in surgical treatment of spinal adhesive arachnoiditis and
      arachnoid cysts].
AB  - Thecaloscopy is less invasive exploration of spinal subarachnoid space with ultra
      thin flexible endoscope and endoscopic fenestration of scars and adhesions.
      Thecalopscopy was used in Russian neurosurgery at the first time. Since 2009 we
      operated 32 patients with following diagnosis: 17--spinal adhesive arachnoiditis
      (8--local forms, 9--diffuse forms), 12--spinal arachnoid cysts (7--posstraumatic
      cysts, 5--idiopathic cysts), 3--extramedullary tumors (thecaloscopic
      videoassistance and biopsy). In all cases we realized exploration of subarachnoid
      space and pathologic lesion with endoscopic perforation of cyst or dissection of
      adhesions using special instrumentation. Mean follow-up in our group was 11.4
      months. Neurological improvement (mean 1.4 by modified Frankel scale, 1.8 by
      Ashworth spasticity scale) was seen in 87% of patients operated for spinal
      arachnopathies. Temporary neurological deterioration (mild disturbances of deep
      sensitivity) was seen in 9% of patients and managed successfully with
      conservative treatment. 1 (3.1%) patient was operated 3 times because of relapse
      of adhesions. There were no serious intraoperative complications (e.g., serious
      bleeding, dura perforation etc). Postoperative complications included 1 CSF
      leakage and 1 postoperative neuralgic pain. Mean term of hospitalization was 7.6
      days. According to our data, we suppose that thecaloscopy is efficient and safe
      method, and should be widely used for spinal arachnopaties, adhesive
      arachnoiditis and arachnoid cysts. Taking into account that adhesive spinal
      arachnoiditis is systemic process and spinal arachnoid cysts can be extended as
      well, thecaloscopy may be regarded as the most radical and less-invasive way of
      surgical treatment existing currently in neurosurgery.

PMID- 24564086
TI  - [Orbitosphenopetroclival meningeomas].

PMID- 24564087
TI  - [Memories of N.Ya. Vasin (1923-1985)].

PMID- 24564088
TI  - Congenital cystic adenomatoid malformation of the lung: a case report and
      diagnostic challenges in a typical African setting.
AB  - Congenital cystic adenomatoid malformation (CCAM) of the lung an entity which
      results from a harmatomatous proliferation of the bronchioles constitutes 25% of
      the all congenital lung anomalies. Majority of cases of CCAM usually present with
      respiratory distress from birth, while others may present with recurrent chest
      infections in childhood or in adulthood. Most reports on CCAM have been on
      caucasian children and the diagnosis of the condition appears to be challenging
      unless there is a high index of suspicion. This report describes the case of a
      child who presented in late infancy and was initially managed as a case of
      hydropneumothorax, however a Computed Tomography (CT) of the chest confirmed
      CCAM. The diagnostic challenges is also addressed.

PMID- 24564089
TI  - Fixed bridge prostheses management of epileptic patients.
AB  - BACKGROUND: Epileptic patients in the course of seizures may suffer damage to or
      loss of teeth and other oral tissues. Moreover, they are at great risk during
      their seizures from aspiration of foreign bodies such as removable dental
      prosthesis or fragments of prosthesis. It is therefore, necessary to provide them
      a tooth replacement option that would be safe and not constitute a source of
      danger in the course of seizures. CASE REPORTS: Two patients are presented in
      this report that lost teeth as a consequence of trauma sustained during seizures.
      They both had porcelain-fused-to-metal (ceramo-metal) fixed bridge prostheses
      fitted to replace the missing teeth. The fixed bridges have been in service for
      seven years without damage despite the fact that the patients still have seizures
      at the same frequency as prior to treatment that are often associated with trauma
      to oral tissues. CONCLUSION: Fixed bridge prostheses are a viable tooth
      replacement option for epileptic patients that do not pose any additional danger
      of being dislodged, swallowed or aspirated in the course of a seizure.

PMID- 24564090
TI  - Left ventricular geometry in Nigerians with type II diabetes mellitus.
AB  - BACKGROUND: Left ventricular hypertrophy is independently associated with
      increased incidence of cardiovascular disease, cardiovascular and all cause
      mortality. In a relatively healthy hypertensive adult population, type II
      diabetes is associated with higher left ventricular mass, concentric left
      ventricular geometry and lower myocardial function independent of age, sex, body
      size, and arterial blood pressure. OBJECTIVE: The study is to investigate left
      ventricular geometry in Nigerians with Type II Diabetes mellitus. METHODS: The
      study design was cross-sectional and it comprised 75 consecutive patients with
      type II diabetes mellitus with or without hypertension. Using a structured pre
      evaluated questionnaire, the demographic and clinical data were obtained. All
      subjects had two dimensional (2D) and 2D derived M-mode echocardiography using
      Sonoline G60s Ultrasound imaging system with 4.2 MHZ transducer equipped with
      simultaneous ECG tracing. RESULTS: A total of 75 consecutive type II diabetic
      patients with or without hypertension were recruited into the study. There were
      18 (24.0%) hypertensive-diabetic and 12 (16.0%) normotensive-diabetic males and
      Thirty-four (45.3%) hypertensive-diabetic and 11 (14.0%) normotensive-diabetic
      were females. Hypertensive-diabetic males had significantly higher left
      ventricular mass compared to normotensive-diabetic counterpart 207.05 +/- 41.5g
      and 156.00 +/- 27.1g P = 0.001. Similarly, left ventricular mass index was found
      to be higher in hypertensive-diabetic males than their normotensive-diabetic
      counterpart 114.50 +/- 29.2g/m2 and 92.28 +/- 20.5g/m2 P = 0.014. Hypertensive
      diabetic female significantly had higher LVM compared to the normotensive
      diabetics 196.06 +/- 41.5g and 161.54 +/- 31.6g P = 0.016. Left ventricular mass
      index was also found to be higher in hypertensive-diabetic female than their
      normotensive counterpart 118.52 +/- 27.8g/m2 and 95.75 +/- 23.0g/m2 P = 0.019.
      Hypertensive-diabetics had predominantly concentric left ventricular hypertrophy
      compared to the normotensive-diabetics 36 (69.2. %) and 5 (21.7%) P = 0.001.
      CONCLUSION: The study reported that hypertensive-diabetics have predominantly
      concentric left ventricular hypertrophy, higher left ventricular mass and left
      ventricular mass index compared to normotensive-diabetic. Female hypertensive
      diabetic had predominantly concentric left ventricular hypertrophy, while male
      hypertensive-diabetic and normotensive-diabetic had predominantly concentric left
      ventricular remodelling.

PMID- 24564091
TI  - Aluminium-induced liver and testicular damage: effects of Piliostigma thonningii
      methanolic leaf extract.
AB  - BACKGROUND: Aluminium is believed to be non toxic and easily eliminated from the
      body, a belief which encourages its use in daily life. However, several studies
      have reported its hepatotoxicity and testicular derangement in animals and
      humans. OBJECTIVE: The protective potential of Piliostigma thonningii (250 mg/kg
      of body weight) methanolic leaf extract on aluminium-induced hepatotoxic and
      testicular damage in Wister rats was studied. METHODS: Toxicity was induced in
      experimental animals via oral route using 0.5 mg of AlCl3 per kg of body weight
      (b.w). The toxicant and the plant extract were administered with the aid of
      gastric intubator for a period of 35 days at 24h interval. Thirty male Wistar
      rats (mean weight, 207 +/- 11.01g) were randomly assigned to three groups: a
      control group treated with 0:5 ml of olive oil (vehicle for the extract) and 1 ml
      of saline (vehicle for the toxicant), a second group treated with 0.5 mg of AlCl3
      (toxicant) per kg bwt and a third group treated with 0.5 mg of AlCl3 and 250 mg
      of P. thonningii extract per kg b.w. The serum activities of liver enzymes:
      alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline
      phosphatase (ALP) along with sperm function indices (sperm count, sperm motility,
      live/dead sperm ratio and total morphological abnormalities) were assessed in the
      animals. RESULTS: AlCl3 ingestion caused a decrease in mean gain in body weight,
      % sperm motility, sperm count and live/dead sperm ratio as well as significant (P
      < 0.05) increase in absolute weight of the liver, total sperm abnormalities, ALT,
      AST and ALP activities as compared to the control rats. The toxicant, however did
      not cause any significant (p < 0.05) change in absolute and relative weights of
      the testis and caudal epididymis of rats as compared to the control rats. Co
      treatment of rats with P. thonningii leaf extract apparently subverted the
      induced-changes. Though, rats co-treated with the extract do not show visible
      signs of protection against AlCl3-induced sperm damage, serum activities of ALT,
      AST and ALP were significantly decreased following oral intake of the extract.
      CONCLUSION: Data of the study suggest that AlCl3 exposure particularly through
      oral route at a dose of (0.5 mg/kg b.w) is toxic and capable of inducing liver
      damage and testicular dysfunction in animals and possibly humans. Interestingly,
      Piliostigma thonningii extract (methanolic) at a dose of 250 mg/kg b.wt) was
      effective in protecting rats from liver damage induced by the toxicant.

PMID- 24564092
TI  - Early outcome of open primary pull through versus staged pull through in
      Hirschsprung's disease: a single centre experience from Nigeria.
AB  - BACKGROUND: The treatment of Hirschsprung's disease has followed a trend from 2
      or 3-staged pull-through (SPT) procedures to a single stage primary pull-through
      (PPT) procedure and from open surgery to laparoscopy-assisted, and trans-anal
      pull through procedures. The (PPT) procedure has the advantage of avoiding a
      stoma and its complications. OBJECTIVE: This study compares the outcomes in open
      PPT and SPT in our centre. METHODS: Retrospective observational study at a single
      centre from Nigeria over a 4year period. RESULTS: Of 46 patients with
      Hirschsprung's disease, 29 patients had pull-through procedures during the study
      period; 19 had SPT and 10 had PPT. There were 21 boys and 8 girls (M:F = 2.6:1).
      Five (17.1%) were diagnosed in the neonatal period and median age at surgery was
      30 months (1 month - 31 yrs). The mean length of hospital stay was 30 days (+/-
      7) in the SPT group while it was 16 days (+/- 3) in the PPT group, p < 0.05.
      Colostomy morbidity such as prolapse and skin excoriation showed statistical
      significant difference compared to other complications associated with pull
      through (p < 0.05); however morbidity from pull-through procedures alone were
      similar. There was no statistically significant difference in post operative
      bowel habit irrespective of type of pull through operation performed (p > 0.05).
      Patients were followed up for between 3 months and 36 months. Two patients died
      giving a mortality rate of 6.7% overall. CONCLUSION: PPT significantly reduced
      both hospital stay and colostomy complications compared to SPT.

PMID- 24564093
TI  - Characterisation of physiotherapy needs in a rural community in South Eastern
      Nigeria.
AB  - BACKGROUND: The majority of the populace in Nigeria resides in rural areas, where
      there is difficulty in accessing rehabilitation services. Rural dwellers are
      often poor and marginalized, and have been reported to have a high level of
      disability and functional dependence. They may therefore be in need of
      rehabilitation. OBJECTIVE: To assess and characterize physiotherapy needs in a
      rural community of South Eastern Nigeria. METHODS: A total of 400 individuals
      participated in this population-based cross-sectional study which included
      'household members' aged 0-5 years and 12 years and above, involving 12 randomly
      selected villages from Nkanu West Local Government of South Eastern Nigeria.
      Distribution of the questionnaire was done by hand on a one-on-one basis, using
      the interviewer style. Information on infants and children was obtained from the
      heads of the households. RESULTS: One hundred and ninety six (49.0%) reported
      ambulatory problems; the problem were mostly associated with the spine 75
      (18.8%), multiple joints 51(12.8%) and lower limbs 43 (10.8%) respectively. The
      highest developmental deficit was reported at three years 6 (18.7%). CONCLUSION:
      There is need to provide affordable community based rehabilitation
      (physiotherapy) outfits in this community.

PMID- 24564094
TI  - Stroke among young adults at the LAUTECH Teaching Hospital, Osogbo, Nigeria.
AB  - BACKGROUND: Stroke in young adults is relatively rare and there are very few
      hospital reports about it in Nigeria. The aetiologic mechanisms of stoke among
      young adults are quite distinct from those of the adults' populations. OBJECTIVE:
      The purpose of this retrospective study was to determine the frequency,
      aetiologic mechanisms and prognosis of stroke among young adults at the LAUTECH
      Teaching Hospital Osogbo Nigeria. METHODS: The study was both retrospective and
      descriptive. Case notes of stroke patients aged 16-45 years managed at the
      LAUTECH Teaching Hospital Osogbo from June 2005 till February 2008 were
      retrieved. Demographic data, clinical profile of stroke, laboratory investigation
      results and treatment outcomes were collated. Clinical diagnosis and
      classification of stroke was mainly clinical using the WHO clinical criteria.
      Only 3 patients had cranial CT scan. RESULTS: Out of the total number of 208
      stroke patients managed during this period, 27(12.9%) were aged 45 years and
      below. This comprised of 17 males and 10 females. The age range was between 23-45
      years. Using the WHO clinical criteria, there were 14 cases of heamorrhagic CVD
      and 13 cases of ischaemic CVD. The three cranial CT scan that were done revealed
      cerebral infarction which was consistent with the clinical diagnosis. Severe
      hypertension was found in 16 (59.2%) patients on admission. 3 patients had
      clinical and electrocardiographic evidence of rheumatic heart disease with
      infective endocarditis. Other risk factors included Sickle cell disease, cardiac
      arrhythmias etc. 8 out of the 27 patients died giving a percentage mortality of
      29.6% and 7 patients were discharged against medical advice. CONCLUSION:
      Heamorrhagic stroke was slightly more frequent than ischaemic CVD. Systemic
      hypertension was also found to be prevalent among these young Nigerian adults
      with stroke. However, it was difficult to unravel the aetiologic mechanisms of
      stroke in this study because of paucity of investigations.

PMID- 24564095
TI  - Effect of health education on knowledge, attitude and practices of personal
      hygiene among secondary school students in rural Sokoto, North West, Nigeria.
AB  - BACKGROUND: Personal hygiene related diseases are serious public health problems
      in developing countries. OBJECTIVE: To assess the effect of health education on
      knowledge, attitude, and practices of personal hygiene among rural secondary
      school students in Sokoto state, north western Nigeria. METHODS: A quasi
      experimental controlled study with pretest and post-test design was carried out.
      A total 120 subjects per group were selected by multistage sampling technique.
      Two pre-tested instruments, structured interviewer-administered questionnaire and
      observer's checklist for personal hygiene practices were used for data
      collection. Health education intervention was carried out one week after baseline
      data collection and repeated after four weeks for the intervention group only.
      Postintervention data collection was carried out in both intervention and control
      groups three months after the 2nd intervention. However, for ethical
      consideration, the control group was also provided with the health education
      intervention similar to that provided to the intervention group. RESULTS: A total
      of 120 and 116 subjects in the intervention and control groups respectively
      participated in all phases of the study. The mean knowledge score (%) of the
      study subjects was high and similar (73.18 +/- 25.82; 77.06 +/- 21.79; p = 0.21)
      in both the intervention and control groups at baseline, but differed very
      significantly (91.16 +/- 11.03; 81.74 +/- 21.78; p < 0.0001) at post
      intervention. The mean attitude score (%) was high but differ significantly (82.6
      +/- 12.73; 86.38 +/- 10.74; p = 0.01) between the intervention and control groups
      at baseline, and further differed very significantly (95.5 +/- 3.66; 86.90 +/-
      10.44; p < 0.0001) at post intervention. The mean reported practice score (%) was
      high but differ significantly (94.86 +/- 3.00; 93.25 +/- 6.31; p = 0.01) between
      the intervention and control groups at baseline, and further differed very
      significantly (96.68 +/- 4.08; 93.7 +/- 6.28; p < 0.0001) at post-intervention.
      The mean observed practice score (%) was high and similar (57.50 +/- 29.65; 61.35
      +/- 28.49; p = 0.31) in both the intervention and control groups at baseline, but
      differed very significantly (88.20 +/- 9.99; 62.10 +/- 26.94; p < 0.0001) at post
      intervention. CONCLUSION: Health education intervention had impact on knowledge
      base, attitude and practice of study subjects in intervention group compared to
      control group. Personal hygiene health education is therefore recommended to be
      taught in secondary schools.

PMID- 24564096
TI  - Evaluation of association between digital dermatoglyphic traits and type-2
      diabetes in Lagos, Nigeria.
AB  - BACKGROUND: Diabetes is a very serious problem in the world today. In particular,
      the incidence of type-2 diabetes is rising in developing countries because of
      life style changes to that of westernized societies. Type-2 diabetes is usually a
      late onset disease. Thus, early identification of risk group individuals through
      a non-invasive method like dermatoglyphics will be very helpful. OBJECTIVE: To
      see whether finger print pattern (dermatoglyphics) is associated with type-2
      diabetes. METHODS: Dermatoglyphic data were obtained from nondiabetic and type-2
      diabetic subjects attending the Diabetic Clinic of Lagos University Teaching
      Hospital (LUTH) using a computer-assisted data capture system. The data were then
      analysed for association between the dermatoglyphic pattern and the subjects'
      health status with respect to type-2 diabetes. RESULTS: Total finger ridge count
      (TFRC) was significantly higher (P < 0.05) in diabetic subjects than in non
      diabetics. Results of cluster analysis suggested that dermatoglyphic pattern is
      associated with type-2 diabetes. CONCLUSION: In view of the association between
      finger print pattern and type-2 diabetes, dermatoglyphics may be used for early
      identification of risk group individuals for surveillance purposes with a view to
      preventing disease onset.

PMID- 24564097
TI  - Reasons and pattern of tooth extraction among patients presenting at a Nigerian
      semi-rural specialist hospital.
AB  - BACKGROUND: Oral health is greatly influenced by health teeth. OBJECTIVE: The
      study is to determine the reasons and pattern of tooth extraction in patients
      seeking care at the oral surgery/Dental clinic in Rasheed Shekoni Specialist
      Hospital, Dutse, Jigawa between January 2010 and December 2011. METHODS: A
      retrospective review of records of dental extraction patients. Patients' records
      were analyzed for demographics, reason(s) for tooth extraction and tooth/teeth
      extracted. RESULTS: During the 2 years study period, 349 patients (M:F = 1.3:1)
      aged 2-65 years (mean = 29.7 years +/- 11.5 SD) had extraction of 377 teeth.
      Dental caries and its sequelae (91.2%) was the most frequent reason for tooth
      extraction across all age groups, followed distantly by periodontal disease
      (3.2%) and recurrent pericoronitis (3.0%). The highest proportion of extraction
      occurred between age 21 to 30 years of age. Mandibular first molars were the most
      commonly extracted tooth due to dental caries, followed by maxillary first and
      mandibular second molars. Mandibular molars were by far the more frequently
      extracted than maxillary molars. CONCLUSION: Dental caries and its sequelae was
      the main reason for removal of teeth in this section of Nigerian population.
      Therefore, there is urgent need to focus on the prevention and treatment of
      dental caries and its sequelae in order to maintain functional and healthy teeth
      throughout life.

PMID- 24564098
TI  - Occupational stress among radiographers in Lagos, Nigeria.
AB  - BACKGROUND: Occupational stress induced injuries occur in various professions
      that require repetitive motion or physical exertion, such as Radiography. The
      injuries may involve body parts such as the neck, the upper back, mid back, low
      back (waist), knee, elbow, wrist and hand and eyes. OBJECTIVE: To assess work
      related injuries medical radiographers are prone to, during practice of the
      profession in relation to their working conditions. METHODS: This study was
      conducted among registered practicing radiographers in Lagos State, South-West,
      Nigeria. Lagos is one of Nigeria's most populated states and economic nerve
      centre of Nigeria. Due to its population, there are many hospitals with
      radiodiagnostic facilities and radiodiagnostic centres which are either
      government or privately owned. Eighty registered radiographers in 21 hospitals
      and diagnostic centres participated in the study. They include three federal
      government owned institutions, three State government owned institutions and
      fifteen privately owned diagnostic centres. The respondents' status were made up
      of 38 males and 42 females where 37 of them were between 20-30 years, 11 were
      between 41-50 years and those above 51 years were 12. RESULTS: The results
      revealed that a majority (91.2%) of respondents stand during the course of their
      work. Waist, neck, heel, wrist and shoulder pains were common among the
      respondents. Some respondents frequently manifest frustration (78.7 %), insomnia
      (52.5 %), difficulty in concentration (56.2%), poor appetite (50.0%), irritation
      (67.5 %) and tension (63.8%) while lesser percentages experience such.
      CONCLUSION: This study showed that occupational stress sites susceptible to work
      induced stress injury. Musculoskeletal strain was the most common type. Waist/
      low back, plantar/heel and wrist pains were also common among radiographers in
      Lagos, Nigeria.

PMID- 24564099
TI  - Pattern and outcome of cases seen at the Adult Accident and Emergency Department
      of the Lagos University Teaching Hospital, Idi-Araba, Lagos.
AB  - BACKGROUND: The accident and emergency department constitutes one of the vital
      entry points of patients into the healthcare facility of the hospital the world
      over. It responds to and manages variety of cases in all the clinical areas and
      thus pr vides an insight to the quality of care available in the health
      institution. OBJECTIVE: The aim of this study is to determine the pattern of
      cases seen as well as the causes of deaths at the adult accident and emergency
      department of the Lagos UniversityTeaching Hospital, Idi-Araba, Lagos. METHODS:
      Retrospective review of records of all patients attended to at the adult accident
      and emergency department of the Lagos University Teaching Hospital in 2009 and
      2010 was carried out. Data spread sheet was used to collect data on demographic
      indices, diagnosis, outcome, date admitted, date discharged and amount paid from
      casualty attendance register and Nurses' report books. Data was collated and
      analysed using Epi-Info version 3.4.1 statistical software package. RESULTS: Out
      of the 5,427 available patients' records reviewed, 4,761(87.7%) were recorded as
      "discharged alive", 546 (10.1%) were recorded as "died", while 120 (2.2%) were
      recorded as "brought in dead". Of those discharged alive, male attendance was
      2,376 (49.10%) while that of the female was 2,385 (50.10%). Majority of these
      patients were aged 20-39 years and the mean age of the patients was 39.96 +/-
      18.22 yrs. Majority of cases seen were medical in origin (53.7%) and highest
      medical case seen was cerebrovascular accident, Commonest cause of death was from
      medical cases [69.2%] (cerebrovascular accident 22.0%). Male mortality was 55.3%
      while female mortality was 44.7%, mean age was 46.86 +/- 17.61. Most affected age
      group was 40 - 59 years (35.4%) and highest number of death was seen in December.
      CONCLUSION: The commonest case seen as well as commonest cause of death was
      cerebrovascular accident. A high number of heart failure, head injuries, road
      traffic accidents, upper gastrointestinal bleeding and post partum haemorrhage
      were also seen as common causes of death.The emergency physician must be well
      trained in skills required for the immediate management of patients with these
      cases.

PMID- 24564100
TI  - Perception of dentine hypersensitivity and its management by a group of Nigerian
      dentists.
AB  - BACKGROUND: Dentists need to be aware of the management of dentine sensitivity in
      view of its high prevalence. OBJECTIVE: The study is to determine by
      questionnaire the perception of dentine hypersensitivity (DH) and its management
      by Nigerian Dentists. METHOD: A structured questionnaire was used to collect data
      from 176 Nigerian Dentists who attended professional dental workshops in Lagos,
      Ife and Jos, Nigeria. RESULTS: The majority (73.3%) of the responding dentists
      claimed to see patients with DH. Nearly half (45.1%) of the dentists mentioned
      cold as the commonest stimulus evoking pain in DH while 56.8% could correctly
      identified the hydrodynamic theory as the commonest theory of tooth
      hypersensitivity. Multifactorial aetiology identified as causing DH included
      tooth wear lesions, periodontal causes and bruxism. Treatment options suggested
      varies but non-invasive was mentioned more than the invasive techniques.
      Sensodyne toothpaste was the commonest desensitising paste mentioned. The
      knowledge of Nigerian Dentists was found to be associated with the specialty of
      the practitioners (p = 0.0004). CONCLUSION: Dental Practitioners, especially the
      General Dental Practitioners should be enthusiastic in updating their knowledge
      of DH and the management. Prevention of DH by the Patients and the Dentists
      should be emphasised.

PMID- 24564101
TI  - Intravesical migration of a failed and forgotten intrauterine contraceptive
      device after 20 years of insertion--a case report.
AB  - Intrauterine contraceptive device (IUCD) is a commonly utilized reversible
      contraceptive technique especially in the developing world. Though effective, it
      is not immune to complications. Migration of the device is a rare but serious
      complication which may be symptomatic or asymptomatic. We report a case of a 45
      yr old woman who had IUCD inserted 20 years earlier and had forgotten about it
      since she subsequently had three full-term pregnancies leading to successful
      vaginal deliveries. The forgotten IUCD was discovered incidentally during
      evaluation of the woman for haematuria as it had migrated to the wall of the
      bladder. The case is reported to increase index of suspicion as detailed clinical
      history is important in evaluating cases of haematuria.

PMID- 24564102
TI  - [Effects of genistein on apoptosis in HCT-116 human colon cancer cells and its
      mechanism].
AB  - OBJECTIVE: To investigate the effects of genistein on cell proliferation and
      apoptosis in HCT-116 human colon cancer cells and its possible mechanism.
      METHODS: After treatment with genistein, cell proliferation was determined by MTT
      assay. Cell cycle, cell apoptosis, intracellular reactive oxygen species ( ROS)
      and mitochondrial membrane potential were determined by flow cytometry.
      Furthermore, ultrastructural change was observed using transmission electron
      microscopy (TEM). RESULTS: Genistein inhibited cell proliferation in a dose- and
      time-dependent manner. Genistein treatment in 0 - 100 micromol/L resulted in G2/M
      cell cycle arrest. The ratio of Sub-G1 increased from (1.63 +/- 0.44)% to (8.33 
      1.51)% (P < 0.01). The ratio of early apoptosis increased from (1.93 +/- 0.32)%
      to (7.25 +/- 0.86)% (P < 0.01). Genistein caused characteristic apoptotic changes
      in TEM observation. Genistein treatment in 100 micromol/L increased intracellular
      ROS level to a peak at 2 h [2 h, (15.53 +/- 1.55)% vs. 0 h, (8.57 +/- 0.35)%, P <
      0.01] and decreased mitochondrial membrane potential to a bottom at 1 h [1 h,
      (0.82 +/- 0.02)% vs. 0 h, (6.70 +/- 0.21)%, P < 0.01). CONCLUSION: Our findings
      indicated that genistein inhibits cell proliferation, induces G2/M cell cycle
      arrest and apoptosis in colon cancer cell line HCT-116, with the increase of
      intracellular ROS level and decrease of mitochondrial membrane potential.

PMID- 24564103
TI  - [Combined effects of T-2 toxin and selenium deficiency on lipid peroxidation in
      rat's brain].
AB  - OBJECTIVE: To explore the effects of T-2 toxin and it's synergy with low selenium
      on lipid peroxidation in rats' brain. METHODS: Early weaning male SD (Sprague
      Dawley) rats were randomly divided into normal group and low-selenium model group
      by weight after 1 week for adaptive feeding, and respectively fed normal diet and
      low-selenium diet. After the low Se model was succeed, the normal group were
      randomly divided into control group, low T-2 group, high T-2 group, the model
      group were randomly divided into low Se group, low Se + low T-2 group, low Se +
      high T-2 group. Then give T-2 toxin to the low T-2 group, low Se + low T-2 group
      at the dose of 0.1 mg/(kg x d), and high T-2 group, low Se + high T-2 group at
      the dose of 0.2 (kg x d), intragastric administration for 4 weeks. We take the
      brain sample, observed the morphological changes of brain tissue after HE
      staining, measured the content of MDA and the activity of GSH-Px to observe the T
      2 toxin' effect of antioxidant on rat brain. RESULTS: The activity of rats' brain
      GSH-Px in all low Se groups were lower than the control group (P < 0.05). The
      content of rats' brain MDA in all experimental group were higher than the control
      group (P < 0.05). In all experimental group, the structure, the neurons, the
      nuclei of rats' brain tissue have varying degrees of damage and destruction.
      CONCLUSION: The single factor of T-2 toxin can cause lipid peroxidation in brain,
      lower the activity of GSH-Px and higher the lever of MDA. The single factor of
      low Se can induce lipid peroxidation in rats' brain, lower the activity of GSH
      Px, higher the level of MDA, With the condition of low Se, the effect of T-2
      toxin on lipid peroxidation in rats' brain was more obviously than the single
      factor. There have synergistic effect T-2 toxin with low Se.

PMID- 24564104
TI  - [Study on the inhibiting effects of equol on MCF-7 cells proliferation and its
      molecular mechanisms].
AB  - OBJECTIVE: To investigate the proliferation inhibition effects of equol on human
      breast cancer cell line MCF-7 and explore its molecular mechanisms. METHODS: MCF
      7 cells were treated with different concentration of equol, including 0.1, 0.5,
      1, 5 and 10 micromol/L. After the treatment, the proliferation rate of cells was
      examined by MTT method and the cell apoptosis percentage and cell cycle phase
      were determined by flow cytometry. The bag-1, bcl-2, VEGF, ERK1/2, p-ERK1/2, p38
      and p-p38 protein were determined using Western blotting. RESULTS: A dose and
      time effect of proliferation inhibition of equol was proved in MCF-7. The MCF-7
      cell apoptosis percentage increased significantly in the groups of equol, and the
      cell cycle arrest in G0/G1 phase. The expression of bag-1, bcl-2, VEGF, p-ERK1/2
      and p-p38 protein were decreased gradually with the increase concentration of
      equol. CONCLUSION: The equol could inhibit the proliferation of the breast cancer
      cell lines MCF-7 and its inhibitory effect may be due to inducing apoptosis,
      arresting the cell cycle in G0/G1 phase, down-regulating the expression of bag-1,
      bcl-2, VEGF, p-ERK1/2 and p-p38 protein.

PMID- 24564105
TI  - [Effects of nano-selenium on cognition performance of mice exposed in 1800 MHz
      radiofrequency fields].
AB  - OBJECTIVE: To study the effects of nano-selenium (NSe) on cognition performance
      of mice exposed to 1800 MHz radiofrequency fields (RF). METHODS: Male mice were
      randomly divided into four groups, control and nano-Se low, middle and high dose
      groups (L, M, H). Each group was sub-divided into three groups, RF 0 min, RF 30
      min and RF 120 min. Nano-se solution (2, 4 and 8 microg/ml) were administered to
      mice of L, M, H groups by intra-gastric injection respectively, 0.5 ml/d for 50
      days, the conctral group were administered with distilled water. At the 21st day,
      the mice in RF subgroup were exposed to 208 microW/cm2 1800 MHz radiofrequency
      fields (0, 30 and 120 min/d respectively) for 30 days. The cognitive ability of
      the mice were tested with Y-maze. Further, the levels of MDA, GABA, Glu, Ach and
      the activities of CAT and GSH-Px in cerebra were measured. RESULTS: Significant
      impairments in learning and memory (P < 0.05) were observed in the RF 120 min
      group, and with reduction of the Ach level and the activities of CAT and GSH-Px
      and increase of the content of GABA, Glu and MDA in cerebrum. NSe enhanced
      cognitive performance of RF mice, decreased GABA, Glu and MDA levels, increased
      Ach levels, GSH-Px and CAT activities. CONCLUSION: NSe could improve cognitive
      impairments of mice exposed to RF, the mechanism of which might involve the
      increasing antioxidation, decreasing free radical content and the changes of
      cerebra neurotransmitters.

PMID- 24564106
TI  - [Study on the effect of deficient ERCC2/XPD gene on the repair of DNA damage
      induced by UVC in CHO cell line].
AB  - OBJECTIVE: To explore the function of ERCC2/XPD in the repair of DNA damage
      induced by UVC. METHODS: Chinese hamster ovary (CHO) cell line including AA8
      (wild-type) and UV5 (mutant type, ERCC2/XPD defective), was selected as a cell
      control model. The cell inhibition rate of AA8 and UV5 after UVC treatment was
      estimated by MTT assay, and DNA repair capacity to difference irradiation
      intensity of UVC in cells after 1 h, 3 h, 6 h, 24 h incubation were measured by
      the Comet Assay and Rad51 immunofluorescence test. RESULTS: As compared to AA8,
      UV5 was more sensitive to UVC, and whose cell viability decreased. Comet assay
      and Rad51 immunofluorescence test results show, DNA damage level of UV5 was more
      serious than AA8. In addition, the DNA damage repair capacity reduced obviously
      compared with AA8. CONCLUSION: DNA damage repair capacity of UV5 cells reduced
      due to ERCC2/XPD defective, indicating us that ERCC2/XPD play a critical role in
      the repair process of DNA damage induced by UVC.

PMID- 24564107
TI  - [Using fractional polynomials to estimate the safety threshold of fluoride in
      drinking water].
AB  - OBJECTIVE: To study the dose-response relationship between fluoride content in
      drinking water and prevalence of dental fluorosis on the national scale, then to
      determine the safety threshold of fluoride in drinking water. METHODS: Meta
      regression analysis was applied to the 2001-2002 national endemic fluorosis
      survey data of key wards. First, fractional polynomial (FP) was adopted to
      establish fixed effect model, determining the best FP structure, after that
      restricted maximum likelihood (REML) was adopted to estimate between-study
      variance, then the best random effect model was established. RESULTS: The best FP
      structure was first-order logarithmic transformation. Based on the best random
      effect model, the benchmark dose (BMD) of fluoride in drinking water and its
      lower limit (BMDL) was calculated as 0.98 mg/L and 0.78 mg/L. Fluoride in
      drinking water can only explain 35.8% of the variability of the prevalence, among
      other influencing factors, ward type was a significant factor, while temperature
      condition and altitude were not. CONCLUSION: Fractional polynomial-based meta
      regression method is simple, practical and can provide good fitting effect, based
      on it, the safety threshold of fluoride in drinking water of our country is
      determined as 0.8 mg/L.

PMID- 24564108
TI  - [A case-control study on the association between cigarette smoking and ischemic
      stroke].
AB  - OBJECTIVE: To investigate the association between cigarette smoking and ischemic
      stroke. METHODS: A case-control study was conducted. Investigators got the
      available information from the cases and controls by questionnaires. Logistic
      regression models were used to analyze the relationship between smoking and
      ischemic stroke in this study. RESULTS: A total number of 1037 cases and 1205
      controls were included in this study. As the results showed, cigarette smoking
      was associated with ischemic stroke (OR = 1.368, 95% CI 1.158-1.616). After
      adjustment for age, body mass index, waist hip ratio, blood pressure, blood
      glucose, blood lipid, stroke family history and alcohol, the relationship between
      smoking and ischemic stroke was still significant (OR =2. 158, 95% CI 1.293
      3.600). And the more you smoke, the more you stroke. Compared with nonsmokers,
      the ORs of smokers with 1-9 / day, 10-19 / day and 20 - / day were 1.097, 1.168
      and 2.950. CONCLUSION: Cigarette smoking is a risk factor for ischemic stroke.

PMID- 24564109
TI  - [Study on establishment of mass spectrometry database of salmonella species by
      matrix-assisted laser desorption/ionization time-of-flight mass spectrometry].
AB  - OBJECTIVE: To establish the mass spectrometry database of Salmonella species by
      matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.
      METHODS: By use of standard stains representing 21 species of Salmonella, a
      reference database was established MALDI-TOF-MS-based species identification. The
      profiles of colonies in the identical culture condition with different times were
      analysed for each of standard strains. To evaluate the database, 200 blind-coded
      isolates were tested by the established database and the original database.
      RESULTS: The positive rate of identification by the original database, the
      established database and conbine-database were 87.5%, 97.0% and 97.5%. 21
      Salmonella strains were divided into 3 types by MALDI-TOF-MS at distance level of
      500. PCA of the reference strains showed difference between them. There were
      little changes of mass spectrometric data of several strains in different culture
      condition. CONCLUSION: The established database could expand the original one and
      be used for identification of Salmonella species. The strategy may be fit for
      other bacteria.

PMID- 24564110
TI  - [Risk and risk factors of suicide attempt after first onset of suicide ideation:
      findings from medical students in grades 1 and 2].
AB  - OBJECTIVE: To examine transition probabilities from first onset of suicide
      ideation to attempt over time among medical students in grades 1 and 2 and risk
      factors in the transition. METHODS: A total of 10 297 college students in grades
      1 and 2 from three medical schools in Anhui province were invited to complete the
      questionnaires, which included history of suicidal behaviors, adverse childhood
      experiences, family history of suicide, sociodemographic characteristics, the
      Beck Depression Inventory, the Beck Anxiety Inventory, the Barratt Impulsiveness
      Scale, the Aggressiveness Questionnaire, and the Social Support Rating Scale.
      Transitions were estimated using life-table analysis. Risk factors were examined
      using Cox regression models. RESULTS: Of the 10,297 participants, 16.52% (n =
      1701) reported lifetime ideation and 1.47% (n = 151) attempt. Cumulative
      probabilities was 8.88% for the transition from first onset of suicide ideation
      to attempt. The riskest probabilites of transition occurred within 1 year after
      onset of ideation (7.02%). 76.16% (n = 115) first attempts occurred within 1 year
      after onset of ideation. Cox regression models analysis found that parents'
      divorce ( OR = 2.32, 95% CI 1.28-4.21), physical abuse (OR = 1.69, 95% CI 1.20
      2.37) , suicidal behavior history of first-degree relatives (OR = 2.02, 95% CI
      1.25-3.25), impulsity (middle /lowest tertile: OR = 1.88, 95% CI 1.15-3.06,
      highest/lowest tertile: OR = 2.09, 95% CI 1.30 -3.36), and highest anxiety scores
      (highest/lowest tertile: OR = 1. 60, 95% CI 1.10-2.33)were significantly related
      to the transition from first onset of ideation to attempt. CONCLUSION: Adolescent
      suicidal ideation signals the recent rsik for suicide attempts. Parents' divorce,
      physical abuse, the suicidal behavior history of first-degree relatives,
      impulsity, and severe anxiety score are risk factors for the transition from
      first onset of suicide ideation to attempt.

PMID- 24564111
TI  - [Analysis of quality of life and its influencing factors among MSM].
AB  - OBJECTIVE: To investigate the quality of life ( QOL) and its influencing factors
      among men who have sex with men ( MSM) in Chongqing city. METHODS: Snowball
      sampling and internet investigation techniques were applied to recruit MSM and
      803 MSM in Chongqing were collected. The WHOQOL-BREF and SSRS questionnaire were
      used among MSM. RESULTS: Scores of the physiological domain, psychological
      domain, social relation domain, environmental domain and total score of QOL were
      (14. 03 +/- 2. 14) (13.38 +/- 2.44), (13.45 +/- 2.88), (12.52 +/- 2.48) and
      (13.29 +/- 2.05), respectively. Except for the environmental domain, scores of
      other domains of MSM were lower than that of common residents. The factors of
      social support and the domains of the quality of life were positive correlation.
      The multivariate analysis indicated that the main factors involved in influenced
      the QOL of the MSM were monthly income and scores of total social support.
      Frequency of condom, objective support, presence of regular homo-sex partners,
      the number of friends in gay circles, presence of regular sexual partner, the
      situation of only child,utilization of support, profession, knowing the VCT or
      not,native place had impacts on a few domains of the QOL. CONCLUSION: According
      to different demographic characteristics, and combining HIV health education and
      psychological intervention is helpful to improve the quality of life among MSM.

PMID- 24564112
TI  - [Analysis of iodine nutrition and thyroid function of adults in urban areas of
      Wuwei city Gansu province].
AB  - OBJECTIVE: To find out the iodine nutrition and thyroid function of adults in
      urban areas of Wuwei city Gansu province and to provide a basis for scientific
      iodine supplementation. METHODS: A cross-sectional survey was performed in 104
      adults in Wuwei city form the April 2009 to January 2010. The morning blood
      samples and one urine samples selected randomly of different people were
      collected and three free triiodothyronine (FT3), free thyroid hormone (FT4),
      total triiodothyronine (TT3), total thyroxine (TT4), the thyroid-stimulating
      hormone (TSH), thyroglobulin antibodies (TGAb), thyroid microsomal antibodies
      (TMAb) in blood samples and iodine in urine samples were detected. RESULTS: The
      medians of urinary iodine were respectively 139.3 microg/L and 212.6 microg/L for
      male and female, female was significantly higher than male, there were
      statisticant differences (P < 0.05). TT3, TT4, FT4, FT3 and TSH's mean values
      were in the normal range, the abnormal ratio of TT3, TT4, FT3, FT4, TSH were
      respectively 1.9%, 1.0%, 3.8%, 1.9%, 16.3%. The positive rate of TGAb and TMAb in
      female were all higher than male, there were statisticant differences (P < 0.05).
      Subclinical hypothyroidism in all thyroid function disorders was most and
      accounted for 14.4% and female were all higher than male (P < 0.05). The survey
      were divided into iodine deficiency group, adequate iodine group, over adequate
      iodine group and iodine excess group for urinary iodine level. The abnormal ratio
      of TT3, TT4, FT3, FT4, TSH in four groups had no statistically differences, but
      the positive rate of TGAb and TMAb raised with increased urinary iodine level.
      Thyroid function disorders occurred in the other three groups except iodine
      deficiency group, and there were statisticant differences. CONCLUSION: Iodine
      nutrition level is appropriate for adults in urban areas, but the female was
      higher than male. Subclinical hypothyroidism in all thyroid function disorders
      was most, the positive rate of TGAb and TMAb raised with increased urinary iodine
      level, the risk of female suffered from thyroid disease was higher than male.

PMID- 24564113
TI  - [Water intake and its influencing factors of children and adolescents in
      Shanghai].
AB  - OBJECTIVE: To describe the total drinking water intake and its influencing
      factors among children and adolescents in Shanghai, and to accumulate basis for
      developing adequate water intakes for children and adolescents in China. METHODS:
      A total of 1454 children and adolescents aged 8-17 years from two districts of
      Shanghai was selected by using stratified random sampling method. The information
      on amounts and types of daily drinking water was recorded by subjects for seven
      consecutive days using a quantitative measurement. Total drinking water was the
      sum of plain water and beverages. RESULTS: The median of total drinking water of
      subjects was 1014 ml/d, and the median of plain water and beverages was 580 and
      339 ml/d, respectively. The consumption of total drinking water, plain water, and
      beverages in boys was significantly higher than that in girls, was increasing
      with aging and in urban was significantly higher than that in suburbs (P < 0.05).
      The obese drank more beverages (P < 0.05). CONCLUSION: The total drinking water
      of children and adolescents in Shanghai was less. To establish adequate intake of
      water, the comprehensive effect of gender, age, BMI and region when should be
      considered.

PMID- 24564114
TI  - [Trend of sugar-sweetened beverage consumption and intake of added sugar in China
      nine provinces among adults].
AB  - OBJECTIVE: To describe sugar-sweetened beverage ( SSB) consumption status and
      intake of added sugar in China nine provinces among adult from 2004 to 2009.
      METHODS: Use of "U.S.D.A. Database for the Added Sugars Content of Selected
      Foods" to calculate the intake of added sugar from sugar-sweetened beverage.
      RESULTS: SSB consumption was basic on the rise. The daily average intake of added
      sugar from SSB was 13.4 g. Men were significantly higher than women, urban was
      higher than rural areas. Added sugar from soft drinks was higher than that from
      fruit juice. CONCLUSION: Added sugar intake level in our country is low relative
      to other developed countries, also did not exceed WHO and the AHA recommends. But
      it's on the rise in generally.

PMID- 24564115
TI  - [Health literacy survey among permanent resident in Daxing District of Beijing].
AB  - OBJECTIVE: To understand status of health literacy and analyze its influencing
      factors among permanent residents in Daxing district of Beijing. METHODS:
      Multistage stratified cluster random sampling method was used to recruit 807
      permanent residents 18-79 years old. A questionnaire was used to collect
      information about normal social-demographic characters,the basic knowledge and
      concept literacy, healthy lifestyle and behavior literacy, and health skill
      literacy and so on. RESULTS: The average awareness rate of health literacy was
      71.1%. In the three aspects of health literacy, the residents' average awareness
      rates of the basic knowledge and concept literacy, healthy lifestyle and behavior
      literacy, and health skill literacy were 66.9%, 77.5% and 72.9%, respectively.
      Only 14.6% of the residents had adequate health literacy. The residents' average
      possession rate of the basic knowledge and concept literacy, healthy lifestyle
      and behavior literacy, and health skill literacy were 13.6%, 51.1% and 52.5%,
      respectively. Health literacy was significantly different among people with
      different education level, occupation and average monthly household income.
      Logistic regression analysis showed that the main factors that influenced health
      literacy were education level and age. Passing percentages were increased with
      education level and age. CONCLUSION: The rate of the residents' health literacy
      was low. There is an urgent need to strengthen health education and promotion in
      the population and spread health literacy related knowledge, in order to improve
      their health literacy level.

PMID- 24564116
TI  - [Nutritional status and related factors of Tujia and Miao minority primary school
      students in Xiangxi Autonomous Prefecture].
AB  - OBJECTIVE: To understand the nutritional status and related factors of Tujia and
      Miao minority primary school students in Xiangxi Autonomous Prefecture and to
      provide refrence for the improvement of minority students' nutritional status.
      METHODS: By the method of layered and random sampling, physique test and
      questionnaire survey were taken to 682 Tujia students and 420 Miao students, the
      nutritional level of students were estimated by the method of height with
      standard weight. Logistic regression analysis was used to analyze the risk
      factors of nutritional status. RESULTS: The moderate malnutrition rate was 4.54%
      and the obesity rate was 11.43%. Logistic regression analysis showed that monthly
      income per capita (OR = 1.368, 95% CI 1.135-1.648) and culture level of fathers
      (OR = 1.332, 95% CI 1.108-1.602) were independent risk factors of malnutrition,
      children with family obesity history (OR =7.688, 95% C15. 134-11.513), monthly
      income per capita (OR = 1.516, 95% CI 1.204-1.910) and culture level of fathers
      (OR = 1.466, 95% CI 1.164-1.846 ) were independent risk factors of overnutrition.
      CONCLUSION: Malnutrition and overnutrition exist in Tujia and Miao students at
      the same time, family obesity history, monthly income per capita and culture
      level of fathers are factors of malnutrition and overnutrition. Nutritional
      education should be taken universal to students and their guardians.

PMID- 24564117
TI  - [Influence of ablactation rats' high calcium intake to the expression of
      uncoupling protein 2 mRNA after adulthood obesity induction].
AB  - OBJECTIVE: To study the influence of early high calcium intake to adulthood
      obesity through detection the expression of uncoupling protein 2 ( UCP2) mRNA in
      muscle by a reverse transcription polymerase chain reaction ( RT-PCR) technique.
      METHODS: 120 male Wistar rats were divided randomly into normal control group,
      high dose calcium group, medium dose calcium group and low doses calcium group,
      with basic diet and high calcium diet for 4 weeks. After intervention, blood fat
      was compared. Subsequently, all rats were fed basic diet for 3 weeks and blood
      fat was compared. Then, normal feed rats were randomly divided into normal
      controls and obesity induction group. Obesity induction group, high dose calcium
      group, medium dose calcium group and low doses calcium group were fed high-fat
      food. After 8 weeks, RT-PCR was used for analysis After obesity induction, weight
      the expression of UCP2 mRNA in muscle. RESULTS: growth of three high calcium
      groups were below obesity induction group, weight growth of low doses and high
      doses of high calcium groups were no difference with normal control group. Serum
      triglyceride levels of high dose high calcium group were significantly lower than
      obesity induction group and no difference with normal control group. Expression
      level of UCP2 mRNA of obesity induction group and high doses of high calcium
      group were obviously lower than normal controls, low dose and medium dose high
      calcium group, medium dose high calcium group' expression was significantly
      higher than normal control group. CONCLUSION: In rats' early life high calcium
      intake can continue to affect adulthood obesity induced by high-fat feed,
      increase expression level of UCP2 mRNA, improve the disorder of blood fat
      metabolism.

PMID- 24564118
TI  - [Analysis mediating effect of self-efficacy between diet-related cognitive and
      behavioral].
AB  - OBJECTIVE: To investigate the influence of self-efficacy between diet-related
      cognitive and behavioral by introducing the concept of mediating effect in
      children and adolescents. METHODS: Using multistage cluster sampling, 9 middle
      and primary school at 1 downtown area and 2 county areas in Guizhou province were
      selected. Referencing to the foreign-related research and design of the
      questionnaire, 1398 students were included. The general survey and the
      correlation analysis about the cognition and self-efficacy of related diet, the
      favorable behavior related health and the unfavorable behavior related health
      were conducted. Using the regression analysis and building the modeling to test
      the mediating effect of self-efficacy of related diet. RESULTS: The average
      scores of the cognition, self-efficacy and beneficial health's behavior of
      related diet were not high. There were significant correlation between the
      cognition and self-efficacy, the cognition and favorable behavior, the self
      efficacy and favorable behavior, the favorable behavior and unfavorable behavior.
      The correlation coefficients were 0.292, 0.248, 0.228 and -0.102 (P < 0.01). The
      self-efficacy had significant indirect mediating effect between diet-related
      cognitive and beneficial health's behavior, the indirect mediating effect was
      24.52% of the total effect. Bringing into the structural equation model to test,
      the indirect effect of self-efficacy (namely mediating effect) was more obvious
      (beta = 0.39, P < 0.01). CONCLUSION: In the actual dietary behavior of children
      and adolescents, improving the self-efficacy can increase the degree of changing
      in behavior which acted by the cognition.

PMID- 24564119
TI  - [Effects of teaseed oil on triglyceride and weight in hypertriglyceridemic
      subjects].
AB  - OBJECTIVE: To investigate the effects of teaseed oil on triglyceride and weight
      in hypertriglyceridemic subjects. METHODS: Twenty-five hypertriglyceridemic
      subjects were enrolled in the study. All subjects were required to ingest 25-30
      g/d of the teaseed oil as cooking oil for 8 consecutive weeks. The height, body
      weight, BMI and the serum oleic acid (OA), total triglyceride (TG) , total
      cholesterol (TC) , blood glucose, alanine aminotransferase (ALT) and aspartate
      aminotransferase (AST) in hypertriglyceridemic subjects were measured. The daily
      total energy, macronutrients intake and activity level were recorded at the
      beginning and ending of the study. RESULTS: Twenty-one subjects completed the
      study. As compared to data at the beginning, the levels of OA in serum and
      dietary intakes of OA, monounsaturated fatty acids significantly increased.
      Polyunsaturated fatty acids intake and body weight, BMI decreased significantly.
      CONCLUSION: Teaseed oil could increase the serum levels of OA and reduce weight
      and BMI in the hypertriglyceridemic subjects with stable dietary intake and
      exercise.

PMID- 24564120
TI  - [Study on the relationship between renal apoptosis and expression of caspase
      protein in fluoride induced rat].
AB  - OBJECTIVE: To study the relationship between death receptor pathway,
      mitochondrion pathway and fluoride-induced apoptosis of renal cell. METHODS: Male
      Sprague-Dawley rats were divided randomly into four groups (control, low
      fluoride, medium-fluoride,and high-fluoride) and administered 0, 50, 100, and 200
      mg/L of sodium fluoride, respectively, via drinking water for 120 days. The
      incidence of dental fluorosis were observed, the body weights and urine fluoride
      levels were measured. Apoptosis was detected by the Flow Cytometry (FCM). The
      expressions of protein of Caspase-3, Caspase-8, Caspase-9, Cyt C were detectedby
      immunohistoehemistry. RESULTS: The apoptosis rate in the fluoride exposed low
      does group,middle dose group and high dose group increased significantly as
      compared with control group. The average optical density value of Caspase-3,
      Caspase-8, Caspase-9 and Cyt C were higher in the fluoride exposed middle dose
      group and high dose group than those in the control group (P < 0.05). CONCLUSION:
      Death receptor pathway and mitochondrion pathway may participate in the process
      of fluoride-induced apoptosis of renal cell.

PMID- 24564121
TI  - [Study on early intervention of compound nutrition for cognitive dysfunction in
      Alzheimer's disease].
AB  - OBJECTIVE: To observe the early prevention effect of the compound nutrients
      recipe for cognitive dysfunction of Alzheimer' s disease model-APP-PSN transgenic
      mouse. METHODS: 36 APP-PSN transgenic mice aged two months randomly were divided
      into the intervention group supplied with compound recipe in the diet and the
      control group fed based feed, the former had high dose and low dose, 12 APP-PSN
      transgenic negative mice aged two months as the negative control were fed based
      feed. After 3 months' intervention, four groups' cognitive functions were
      evaluated using the Morris water maze, active avoidance experiment and jumping
      stair experiment. RESULTS: There was not statistically different between all the
      four groups for the weight and food intake. Compared with the control group,
      Morris water maze's incubation period of the intervention group was lower
      obviously, and jumping stair experiment's incubation period of the intervention
      group was higher obviously. In the active avoidance experiment, the high and low
      dose intervention group' s conditioned response accounted about 46.67% and 45.00%
      respectively, and the control group's conditioned response accounted about
      20.83%. The differences of the three behavioral experiments between control group
      and intervention group had the statistical significance (P < 0.05), so the same
      as between control group and negative control group (P < 0.05). And there was no
      difference between intervention group and negative control group for the three
      behavioral experiments. CONCLUSION: The early supplementation with compound
      nutrition could postpone the occurrence and development of Alzheimer' s disease
      mice model's cognitive dysfunction.

PMID- 24564122
TI  - [Chronotoxicity of 1800 MHz microwave radiation on sex hormones and
      spermatogenesis in male mice].
AB  - OBJECTIVE: To study the chronotoxicity of 1800 MHz micrwave radiation on the male
      reproductive system. METHODS: Sixty healthy male C57 mice with circadian rhythm
      in a 12:12 h light-dark photoperiod were divided into false radiation group
      (Sham) and microwave radiation (MR) group exposed to 1800 MHz RF at 208
      microW/cm2 power (SAR: 0 .2221 W/kg) density at different zeitgeber times of a
      day (ZT01:00, ZT05:00, ZT09 : 00, ZT13: 00, ZT17 : 00, ZT21 : 00) for continuous
      32 days with 2 h/d. The testicular sperm head was counted with a microscope, and
      serum testosterone (T) and estradiol (E2) levels were measured by ELISA method.
      RESULTS: Compared with the sham group,microwave radiation induced reduced level
      in testicular sperm head count and serum testosterone, while the level of serum
      estradiol increased. Also, the circadian rhythms of testicular sperm head count
      and estradiol disappeared after the microwave radiation. CONCLUSION: 1800 MH2
      microwave radiation may disturb the level as well as circadian rhythmicity of the
      reproductive functions in male mice.

PMID- 24564123
TI  - [Identification of benzoic acid, sorbic aicid and dehydroacetic acid residues in
      alcoholic drinks and beverages].
AB  - OBJECTIVE: To establish a qualitative system for the identification of benzoic
      acid, sorbic acid and dehydroacetic acid residues in alcoholic drinks and
      beverages by ultra-fast liquid chromatography coupled with electrospray
      ionization tandem mass spectrometry (UFLC/ESI-MS/MS). METHODS: After the sample
      was extracted, the separation was performed by UFLC and the cracking was used by
      the optimized ESI-MS/ MS conditions. Confirmatory detection was carried out by
      the principle of three qualitative ions and retention time using an UFLC-MS/MS in
      the negative electrospray ionization mode. RESULTS: The MS/MS fragment ions were
      reliable and steady under the suitable conditions, the cracking ways to the
      parent ions and fragment ions were clear. Qualitative ion pairs were m/z 121-->77
      and m/z 121-->59 for benzoic acid, m/z 111-->67 and m/z 111-->41 for sorbic acid,
      m/z 167-->83 and m/z 167-->123 for dehydroacetic acid. The limits of quantitation
      (LOQs) were 0.02, 0.05 and 0.02 mg/L for benzoic acid, sorbic acid and
      dehydroacetic acid, respectively. CONCLUSION: The established method was rapid,
      accurate and sensitive, it is suitable for confirmation for benzoic acid, sorbic
      acid and dehydroacetic acid residues in alcoholic drinks and beverages.

PMID- 24564124
TI  - [Determination of ethyl carbamate in wine by HPLC-FLD].
AB  - OBJECTIVE: To evaluate the method for determining ethyl carbamate (EC) in wine by
      HPLC-FLD. METHODS: Samples were derived and determined by HPLC with a
      fluorescence detector. Using a Agilent TC-C18 (250 mm x 4.6 mm x 5 microm) column
      and a mixture of CH3CN-0.02 mol/L CH3COONa as mobile phase for gradient elution.
      The incidence light wavelength was 233 nm, emission wavelength was 600 nm. The
      fluorescence reaction time was 30 min. The contents were calculated with an
      external standard. RESULTS: The linearity was good in the ranges of 10-500
      microg/L for EC. The average recovery rates of EC was 93.7%-106.0%. The RSD was
      1.4%-2.8%, and the limit of quantification was 15 microg/L. GC-MS and HPLC-FLD
      were compared to evaluate for determining EC content in wine. CONCLUSION: The
      HPLC-FLD method was simple, accurate and suitable for the determination of EC in
      multitudinous wine.

PMID- 24564125
TI  - [Association of leptin gene-2548 G/A polymorphism with obesity: a meta-analysis].
AB  - OBJECTIVE: To examine the association between a common single nucleotide
      polymorphism identified in the 5' untranslated region of leptin gene (LEP-2548
      G/A SNP) and obesity. METHODS: Meta-analysis of published studies, included if
      subjects were genotyped at polymorphism LEP-2548 G/A and both obese and nonobese
      subjects were selected, based on a reported cutoff BMI limit. Meta-analysis of
      the total and subgroup populations was conducted using dominant and recessive
      models, and OR and 95% CI were calculated in the fixed-effect model. I2 statistic
      was calculated to examine heterogeneity, and publication bias was evaluated by
      Egger test. RESULTS: After testing each control group for Hardy-Woinberg
      equilibrium, the final selection enrolled 11 studies, including 5210 subjects
      (2541 obesity subjects and 2669 healthy). In the combined analysis of all
      eligible studies, none significant association was identified between LEP-2548
      G/A SNP and obesity either in dominant model or the recessive one with pooled
      odds ratios 1.14 (95% CI 0.98-1.31, P = 0.08) and 1.03 (95% CI 0.85-1.25, P =
      0.76). However, subgroup analysis found a significant association of GG
      homozygote in American population [OR = 1.53 (95% CI 1.17-2.00), P = 0.002]. No
      significant evidence was found in other populations. DISCUSSION: This first
      metaanalysis of data from published studies did not detect any association
      between the polymorphism of LEP-2548 G/A and risk of obesity in overall
      population. Nevertheless, the presence of the GG genotype in the gene appears to
      be a significant risk factor for obesity in American.

PMID- 24564126
TI  - [Meta-analysis on the relationship between Chinese children's intelligence and
      excessive iodine].
AB  - OBJECTIVE: To evaluate the relationship between Chinese children's intelligence
      and excessive iodine. METHODS: A computerized literature search was carried out
      to collect articles published before 2013. The study type was controlled
      experimental design. And then the statistical analysis was conducted by using
      RevMan 5.0 software. RESULTS: A total of 20 controlled studies were included in
      Meta-analysis. The results showed that iodine content in 601 -900 microg/L (MD = 
      2.00, 95% CI -3.97, -0.03) and greater than 900 microg/L (MD = -2.77, 95% CI 
      4.02, -1.52) would reduce the intellectual level of children. Iodine content in
      150-300 microg/L (MD = 0.33, 95% CI -0.76, 1.42) and 301-600 microg/L (MD = 
      1.09, 95% CI -4.80, 2.63) had not statistically significant. The results of dose
      response analysis revealed that the possibility of lower intelligence would
      increase by 57% (OR = 1.57, 95% CI 1.36, 1.78) when there was an increase of 200
      microg/L in iodine content. CONCLUSION: Iodine content that was greater than 600
      microg/L would reduce the intellectual level of children.

PMID- 24564127
TI  - [Multi-scale and multi-parameter spatial distribution patterns of Seriphidium
      terrae-albae and Artemisia songarica populations in Gurbantunggut Desert of
      Northeast China].
AB  - The researches on the plant population spatial pattern were mostly based on 0-D
      plant point (0-D IND) or 0-D plant count, and only a few was based on the 2-D
      projective cover (2-D PC) and 3-D aboveground biomass (3-D AGB reflected by
      canopy volume). Until now, the plant population spatial distribution patterns
      incarnated by these parameters were still unclear. Taking the widely distributed
      small semi-shrubs Seriphidium terrae-albae and Artemisia songarica in
      Gurbantunggut Desert of Northwest China as test objects, this paper studied the
      IND, PC, and AGB of each individual at two sampling plots. Through six-scale
      division of plot coordinate system with GIS, and by using aggregation analysis,
      coefficient of variation (CV) , and a scaling exponent between the CV and six
      scales, the characteristics of the population spatial distribution patterns with
      the above mentioned parameters were comparatively analyzed. At all scales, the
      IND (except for the S. terrae-albae population at 0.5 m scale) and the AGB of the
      two shrubs all presented a clumped distribution, and the aggregation intensity
      increased' with increasing scale. However, the PC had a uniform distribution
      (except for the A. songarica population at 5 and 8 m scales). With increasing
      scale, the CV values of the two shrubs decreased. The absolute value of scaling
      exponent (k value) of the IND was higher than those of the PC and AGB, and there
      was no significant difference in the k values between the PC and AGB, indicating
      that the scale variation scope of the struc- tural complexity of the IND was
      larger than that of the PC and AGB. The k value of each parameter for S. terrae
      albae was higher than that for A. songarica, which could be related to the
      populations' interspecific relationship and plant size. In sum, the IND and AGB
      had similar spatial patterns, while the PC and AGB had almost same spatial
      pattern complexity and scale change characteristics.

PMID- 24564129
TI  - [Effects of topography on seedling regeneration in a mixed broadleaved-Korean
      pine forest in Xiaoxing'an Mountains, Northeast China].
AB  - To explore the responses of forest seedlings to topographic heterogeneity, nine
      hundreds of 4 m2 (2 m x 2 m) quadrats with perennial seedlings (H > or = 30 cm,
      DBH < 1 cm) were installed in a 9 hm2 plot in a typical mixed broadleaved-Korean
      pine forest in Xiaoxing' an Mountains. Based on the investigation data in 2006,
      2008, and 2010, the effects of topography on the seedling establishment were
      studied. There were a total of 26 tree species in these quadrats. In 2006, 2008,
      and 2010, the total number of the tree seedlings was 4514, 6464, and 5611
      individuals x hm(-2), respectively, among which, the seedlings of the top 10
      species occupied >90% of the total. Topography had significant effects on the
      seedling distribution of the 8 major tree species. For Syringa reticulate var.
      mandshurica, Abies nephrolepis, Acer mono, Ulmus japonica, A. ukurunduense, Tilia
      amurensis, and A. tegmentosum, the spatial distribution of the seedlings was
      consistent with that of grown trees; but for Pinus koraiensis, the spatial
      distribution of seedlings was inconsistent with that of the grown trees. The
      mortality of S. reticulate var. mandshurica, A. nephrolepis, U. laciniata, A.
      tegmentosum, and T. amurensis seedlings was significantly correlated with the
      topography. The recruitment of S. reticulate var. mandshurica, U. japonica, P.
      koraiensis, A. nephrolepis, Fraxinus mandshurica, A. mono, and T. amurensis
      seedlings was also significantly correlated with the topography.

PMID- 24564128
TI  - [Effects of nitrogen and phosphorus fertilization on litterfall production and
      nutrient dynamics in a Schima superba forest in Zhejiang Province of East China].
AB  - In 2011, an investigation was made on the litterfall production and nutrient
      dynamics in a phosphorus-limited subtropical evergreen broadleaved forest
      dominated by Schima superba in Tiantong, Zhejiang Province of East China under
      different levels of nitrogen (N) and phosphorous (P) fertilization. After the N
      and P fertilization, the annual litterfall production ranged from 6.82 to 8.30 t
      x hm(-2) x a(-1), with three peaks in May or June, August, and October,
      respectively. Under fertilization, the annual average N and P concentrations of
      the litterfall (except the annual average N concentration under P fertilization)
      increased, and had a seasonal variation. There were no significant differences in
      the nitrogen return amount (60.05-71.47 kg x hm(-2) x a(-1)) and phosphorus
      return amount (2.94-3.93 kg x hm(-2) x a(-1)) of the litterfall among different
      treatments. As compared to the control, the N:P ratio of the litterfall under
      fertilization was higher at the beginning of the experiment (spring, 2011), but
      lower in the winter, 2011, indicating that nitrogen and phosphorus fertilization
      could alter the original nitrogen and phosphorus limited conditions of the
      studied forest ecosystem.

PMID- 24564130
TI  - [Species composition and main populations spatial distribution pattern in Korean
      pine broadleaved forest in Xiaoxing' An Mountains of Northeast China].
AB  - Taking the Korean pine broadleaved forest in Liangshui Nature Reserve of
      Heilongjiang Province, Northeast China as test object, this paper studied the
      species composition and diameter class structure, and by using point pattern
      analysis, analyzed the spatial distribution pattern and spatial association of
      the main populations. In the Reserve, there were a total of 16 species with
      diameter greater than 1 cm in tree layer, and great differences were observed in
      the densities of main populations. Coniferous trees such as Pinus koraiensis and
      Abies nephrolepis were dominant. The diameter class structure of the populations
      presented as an inverse "J" curve, indicating a good regeneration across the
      community. The main populations were mostly in aggregated distribution pattern,
      except that the P. koraiensis populations at the scales of 19-21 m and 44 m as
      well as the Acer tegmentosum populations close to the largest research scale were
      in random distribution. The P. koraiensis populations at all research scales were
      approximately in random distribution, and had the minimum aggregation. A.
      nephrolepis, Tilia amurensis, and A. tegmentosum populations all presented a
      random distribution trend. Except that the P. koraiensis and A. nephrolepis at 2
      3 m scale and the A. nephrolepis and A. tegmentosum populations at 37-81 m scale
      had significant positive association, no significant associations were observed
      between other populations. All the tree species presented an overall non
      significant positive association.

PMID- 24564131
TI  - [Spatial variation of non-structural carbohydrates in Betula platyphylla and
      Tilia amurensis stems].
AB  - Taking the two diffuse-porous tree species Betula platyphylla and Tilia amurensis
      in a temperate forest in Northeast China as test objects, this paper studied the
      spatial variation of the non-structural carbohydrates (NSC) concentrations in the
      stem xylem after leaf-fall. For the two tree species, the concentrations of total
      non-structural carbohydrate (TNC, soluble sugars plus starch) and soluble sugars
      in the stem xylem decreased gradually with the increasing depth from cambium to
      pith, whereas the starch concentration showed little radial variation. There was
      still a substantial amount of NSC in the inner wood close to pith. The
      concentrations of the NSC in the two species stems decreased gradually from the
      stump to the breast height, and then increased vertically. The maximum
      concentrations of the TNC, soluble sugars, and starch occurred at different
      heights, depending on the species and the TNC components. The ratio of sugar to
      starch showed a contrasting vertical trend for the two species, i. e., increasing
      from the stump to the top for B. platyphylla, but decreasing for T. amurensis.
      The estimation error of the stem NSC storage was mainly from the axial variation,
      and then, from the radial variation of NSC concentration. The TNC concentration
      (1.0% dry mass) in the stem of shade-intolerant species B. platyphylla was
      significantly lower than that (4.3% dry mass) of shade-tolerant species T.
      amurensis, which could be related to their different life-history strategies.
      Applying the sampling protocols considering the axial and radial variations of
      NSC could effectively reduce the potential uncertainty in estimating the NSC
      storage at tree or stand level.

PMID- 24564132
TI  - [Net carbon exchange and its environmental affecting factors in a forest
      plantation in Badaling, Beijing of China].
AB  - By using eddy covariance technique, a year-round (November, 2011-October, 2012)
      continuous measurement of net ecosystem carbon dioxide exchange (NEE) was
      conducted in a 4-year old mixed forest plantation in Badaling of Beijing. The
      forest plantation ecosystem was a net carbon sink in July and August, but a
      carbon source in the rest months. The monthly net carbon loss and uptake were the
      largest in April and July, respectively. The annual net ecosystem productivity
      was (-256 +/- 21) g C x m(-2) x a(-1), in which, the ecosystem respiration was
      (950 +/- 36) g C x m(-2) x a(-1), and the gross ecosystem productivity was (694
      +/- 17) g C x m(-2) x a(-1). The nighttime NEE increased exponentially with the
      soil temperature at 10 cm depth, with the estimated temperature sensitivity of
      ecosystem respiration (Q10 ) being 2.2. During the growth season (May-September),
      the daytime NEE increased with photosynthetically active radiation (PAR) as
      described by the Michaelis-Menten rectangular hyperbola. The ecosystem quantum
      yield varied seasonally, ranging from 0.0219 micromol CO2 x micromol(-1) in May
      to 0.0506 micromol CO2 x micromol(-1) in July. The maximum carbon assimilation
      rate and the average daytime respiration followed the seasonal trends of PAR and
      air temperature. In July and August, vapor pressure deficit and soil moisture
      played a significant role in determining daytime NEE.

PMID- 24564133
TI  - [Estimation of carbonaceous gases emission from forest fires in Xiao Xing'an
      Mountains of Northeast China in 1953-2011].
AB  - Based on the forest resources investigation data and the forest fire inventory in
      1953-2011, in combining with our field research in burned areas and our
      laboratory experiments, this paper estimated the carbonaceous gases carbon
      dioxide (CO2), carbon monoxide (CO), methane (CH4), and nonmethane hydrocarbons
      (NMHC) emission from the forest fires in Xiao Xing' an Mountains of Heilongjiang
      Province, Northeast China in 1953-2011. The total carbon emission from the forest
      fires in the Xiao Xing'an Mountains in 1953-2011 was 1.12 x 10(7) t, and the
      annual emission was averagely 1.90 x10(5) t, accounting for 1.7% of the annual
      average total carbon emission from the forest fires in China. The emission of
      CO2, CO, CH4, and NMHC was 3.39 x 10(7), 1.94 x 10(5), 1.09 x 10(5), and 7.46 x
      10(4) t, respectively, and the corresponding annual average emission was 5.74 x
      10(5), 3.29 x 10(4), 1.85 x 10(3), and 1.27 x 10(3) t, accounting for 1.4%, 1.2%,
      1.7%, and 1.1% of the annual carbonaceous gases emitted from the forest fires in
      China, respectively. The combustion efficiency and the carbon emission per unit
      burned area of different forest types decreased in order of coniferous forest >
      broad-leaved forest > coniferous broadleaved mixed forest. Some rational forest
      fire management measures were put forward.

PMID- 24564134
TI  - [Effects of air temperature and soil moisture on flavonoids accumulation in
      Ginkgo biloba leaves].
AB  - Taking the 2-year old Ginkgo biloba seedlings as test materials, a pot experiment
      was conducted in an artificial climate chamber to study the effects of air
      temperature and soil moisture on the flavonoids accumulation in leaves. Three
      levels of air temperature (15/5 degrees C, 25/15 degrees C, and 35/25 degrees C
      day/night) and three levels of soil moisture (55%-60%, 40%-45%, and 30%-35% of
      field capacity) were installed, yielding nine temperature-soil moisture
      combinations. Under the three levels of soil moisture, the quercetin, kaempferol,
      isorhamnetin, and total flavonoids contents in the leaves were higher at 15/5
      degrees C than at 25/15 degrees C and 35/25 degrees C. Soil moisture had minor
      effects on the flavonoids accumulation. The leaf kaempferol content was the
      highest, followed by quercetin and isorhamnetin. The total flavonoids yield per
      plant at 35/25 degrees C was higher than that at 15/5 degrees C and 25/15 degrees
      C. It was suggested that to adopt appropriate soil covering and watering before
      harvesting to decrease the ambient temperature could benefit the enhancement of
      leaf flavonoids content and the improvement of per unit area flavonoids
      production in G. biloba leaf-harvesting plantation.

PMID- 24564135
TI  - [Effects of different drip irrigation modes on root distribution of wine grape
      'Cabernet Sauvignon' in desert area of Northwest China].
AB  - To study the effects of different drip irrigation modes on the wine grape root
      distribution is the basis of formulating fertilization, irrigation, and over
      wintering management practices for wine grape. Taking the wine grape "Cabernet
      Sauvignon" as test material, this paper studied the effects of different water
      saving irrigation modes (drip irrigation under straw mulching, drip irrigation
      under plastic mulching, double-tube drip irrigation, and single-tube drip
      irrigation) on the root distribution of wine grape in the desert area of
      Northwest China, with the conventional furrow irrigation as the control. The root
      system of the "Cabernet Sauvignon" was distributed from 0 to 70 cm vertically,
      and from 0 to 120 cm horizontally. With double-tube drip irrigation, the root
      amount was the largest (138.3 roots per unit profile), but the root vertical
      distribution scope was narrowed by 20 cm, as compared to the control. Drip
      irrigation with straw mulching increased the root amount significantly, and
      increased the root horizontal distribution scope by 9.1%, as compared to the
      control. No significant difference was observed in the root number and root
      horizontal distribution scope between the drip irrigation under plastic mulching
      and the control, but the root vertical distribution scope with the drip
      irrigation under plastic mulching decreased by 20 cm. Single-tube drip irrigation
      increased the root number significantly, but had lesser effects on the root
      vertical or horizontal distribution, as compared to the conventional irrigation.
      It was suggested that the drip irrigation under straw mulching could be the best
      water-saving practice for the wine grape "Cabernet Sauvignon" in the study area.

PMID- 24564136
TI  - [Effects of different long-term fertilization patterns on Fuji apple yield,
      quality, and soil fertility on Weibei Dryland, Shaanxi Province of Northwest
      China].
AB  - A 7-year (2003-2010) located field experiment was conducted to evaluate the
      effects of different long-term fertilization patterns on the Fuji apple yield,
      quality, and soil fertility on the Weibei Dryland, Shaanxi Province of Northwest
      China. Seven treatments were installed, i. e., no fertilization (CK), inorganic P
      and K fertilization (PK), inorganic N and K fertilization (NK), inorganic N and P
      fertilization (NP), inorganic N, P, and K fertilization (NPK), swine manure (M),
      and half inorganic N, P, and K combined with half swine manure (NPKM). Each
      treatment had three replications. Fertilization increased the apple yield. The
      average yield in the 7 years under fertilization was increased by 14.4%-63.8%, as
      compared to the CK. The average yield decreased in the order of NPKM > NPK > or =
      M > NP > or = NK > PK > CK. In treatments NPKM, M, and NPK, the fruit sugar/acid
      (S:A) ratio, vitamin C, soluble solid, and hardness tended to be increased with
      time, with a smaller yearly fluctuation in treatments NPKM and M. In treatment
      NPKM, the S:A ratio and vitamin C increased by 30.9% and 17.5%, respectively
      after five years, as compared to the CK. Long-term rational fertilization
      increased the soil organic matter (SOC) content in 0-20 cm layer, with the
      largest increment in treatments NPKM and M (28.8% and 29.3%, respectively). The
      soil available N, P, and K contents in all layers in treatments NPK, NPKM, and M
      increased significantly, and the soil available N content in 0-20, 20-40, and 40
      60 cm layers in treatment NPK was increased by 22.7%, 37.3%, and 53.4%,
      respectively. As compared to treatment NPK, the soil available P content in
      treatment NPKM was increased by 18.7%. In all fertilization treatments, the soil
      available Pcontent was significantly higher in upper layer than in lower layer.

PMID- 24564137
TI  - [Effects of shading on dry matter accumulation and nutrient absorption of summer
      maize].
AB  - Taking summer maize cultivars Zhenjie 2 (ZJ2), Denghai 605 (DH605), and Zhengdan
      958 (ZD958) as test materials, a field trial was conducted to study the effects
      of shading on the dry matter accumulation and nitrogen (N), phosphorus (P) and
      potassium (K) absorption of summer maize. Four treatments were installed, i. e.,
      shading from flowering stage to maturity stage (S1), shading from six-leaf stage
      to flowering stage (S2), shading all through the growth season (S3), and no
      shading (CK). After shading, the grain yield and dry matter accumulation
      decreased significantly, and the decrement was related to shading period, showing
      S3 > S1 > S2. The grain yield in treatments S1, S2, and S3 was averagely 61.6%,
      25.3%, and 92.8% lower than that of CK, respectively, indicating that the effects
      of shading after flowering were greater than those of shading before flowering.
      The responses of different cultivars to shading presented a similar trend. The
      nutrient absorption of summer maize before flowering stage showed K > N > P, and
      the nutrient absorption amount of whole plant showed N>K>P. After shading, the N
      and P absorption decreased significantly. The plant relative N and P absorption
      in different treatments had somewhat increase, because the decrement of dry
      matter accumulation after shading was larger than that of N and P absorption, as
      compared with the control. After shading, the plant K absorption decreased
      significantly, and the decrement in S2 was larger than that of dry matter
      accumulation. Shading before flowering stage had larger effects on the plant K
      absorption than on the N and P absorption.

PMID- 24564138
TI  - [Present situation of rice fertilization in qin-ba mountainous area of Southern
      Shaanxi, China].
AB  - In order to understand the present situation of rice fertilization and the
      existing problems in the farmers' nutrient resources input in the Qin-Ba
      mountainous area of southern Shaanxi, the survey data from 2854 households in 11
      counties of this area in the project "soil testing and formulated fertilization
      in 2006-2009" were analyzed and evaluated, and the countermeasures for the
      existing problems in the farmers' nutrient resources input were proposed. In the
      study area, the average rice yield was 7822 kg x hm(-2) per year, and the ratio
      of the households obtained the medium level yield was up to 50.9%. The input of
      the total fertilizers N, P2O5, K2O was 169, 68, and 54 kg x hm(-2), and the
      chemical fertilizer rate was 159, 62, and 45 kg x hm(-2), with the partial factor
      productivity (PFP) of the N, P2O5, and K2O being 51.52, 135.69, and 158.26 kg x
      kg(-1), respectively. According to the nutrient fertilization level, the
      proportion of the households fertilized with rational level of chemical N, P2O5,
      and K2O occupied 48.0%, 42.4%, and 7.2%, that of the households fertilized with
      excessive level was 22.6%, 11.2%, and 0.6%, and the proportion of the households
      fertilized with insufficient level occupied 29.4%, 46.5%, and 92.2%,
      respectively. The rice yield in the Qin-Ba mountainous area could be increased by
      77 thousand tons if the households fertilizing with insufficient level of
      chemical NPK fertilizers increased the fertilization rate to a rational level.
      The existing problems in the farmers' nutrient resources input were mainly the
      coexistence of excessive and insufficient application of nitrogen and phosphate
      fertilizers and the insufficient input of potassium fertilizer and organic
      manure. In the rice fertilization in this area, the focus would be the balanced
      application of nitrogen and phosphate fertilizers, the increase of the
      fertilization rates of potassium fertilizer and organic manure, and the increase
      of top dressing, especially potassium.

PMID- 24564139
TI  - [Effects of exogenous silicon on the pollination and fertility characteristics of
      hybrid rice under heat stress during anthesis].
AB  - Taking two medium-maturing indica rice hybrids Jinyou 63 and Shanyou 63 as test
      materials, this paper studied the effects of applying silicon fertilizer on the
      flag leaf chlorophyll content, photosynthetic properties, antioxidant enzyme
      activities, malondialdehyde (MDA) content, pollen vigor, anther acid invertase
      activity, pollination, and seed-setting of hybrid rice under the heat stress
      during anthesis. This study was conducted in pots and under growth chamber.
      Soluble solution of silicon fertilizer applied as Na2SiO3 x 9H2O was sprayed on
      the growing plants after early jointing stage, with three times successively and
      at an interval of one week. The pots were then moved into growth chamber to
      subject to normal temperature vs. high temperature (termed as heat stress) for
      five days. In treatment normal temperature, the average daily temperature was set
      at 26.6 degrees C, and the maximum daily temperature was set at 29.4 degres C; in
      treatment high temperature, the average and the maximum daily temperature were
      set at 33.2 degrees C and 40.1 degrees C, respectively. As compared with the
      control, applying silicon increased the flag leaf chlorophyll content
      significantly, improved the net photosynthetic rate and stomatal conductance,
      decreased the accumulative inter- cellular CO2 concentration, improved the leaf
      photosynthesis, reduced the MDA content, and improved the activities of SOD, POD
      and CAT under heat stress. In addition, applying silicon improved the anther acid
      invertase activity and the pollen vigor, increased the anther basal dehiscence
      width, total number of pollination per stigma, germinated number, germination
      rate of pollen, and percentage of florets with more than 10 germinated pollen
      grains, decreased the percentage of florets with fewer than 20 germinated pollen
      grains, and thus, alleviated the fertility loss of Jinyou 63 and Shanyou 63 under
      heat stress by 13.4% and 14.1%, respectively. It was suggested that spraying
      exogenous silicon in the early growth period of rice could mitigate the decrease
      of seed-setting at flowering stage, and improve the heat resistance of hybrid
      rice.

PMID- 24564140
TI  - [Mechanisms of subspecies differentiation in a filial generation of rice indica
      japonica hybridization under different ecological conditions].
AB  - Indica-japonica hybridization is one of the most important breeding methods in
      China, whereas identifying subspecies differentiation mechanisms is the key in
      indica-japonica hybridization breeding. By using InDels (Insert/Deletion) and
      ILPs (Intron Length Polymorphism), an analysis was made on the F6 populations
      derived from the hybridization of indica-japonica (Qishanzhan/Akihikari) planted
      in Liaoning and Guangdong provinces and generated by bulk harvesting (BM), single
      seed descent methods (SSD), and pedigree method (PM). No segregation distortion
      was observed for the BM and SSD populations. The frequency distribution of
      japonica kinship percentage (Dj) was concentrated in 40%-60%. The PM populations
      in the two provinces presented indica-deviated distribution (30%-55%), with
      significant difference between Guangdong (38%) and Liaoning (42%). In addition,
      there was a significant positive correlation between the Dj and the kinship of
      functional gene regions in the BM and SSD populations. However, part of the
      positive correlation was broken in the PM populations that showed a regular
      distribution in the genotype patterns of indica and japonica loci. The above
      results demonstrated that artificial selection could be the main factor affecting
      the population differentiation in indica-japonica hybridization, and, with the
      synergistic effect of natural selection, induced the phenomenon of segregation
      distortion. There existed a close relationship between the differentiation of
      subspecies and the important agronomic traits, which could be the main reason why
      indica-japonica hybridiation breeding could not achieve the expected effect of
      combining the two subspecies advantages.

PMID- 24564141
TI  - [Photosynthetic and water physiological characteristics of weedy rice in northern
      China].
AB  - Weedy rice is an important germplasm source of rice, which has the
      characteristics of cold-, drought-, and barren tolerance. Taking 88 accessions of
      weedy rice and 4 varieties of cultivated rice in northern China as test
      materials, this paper studied the photosynthetic characteristics (photosynthetic
      rate, transpiration rate, and stomatal conductance), water physiological
      characteristics, and their interrelationships of weedy rice in northern China.
      There existed greater differences in the photosynthetic and water physiological
      characteristics among the weedy rice accessions, possessing abundant diversity.
      The photosynthetic rate of the accessions was from 12.47 micromol CO2 x m(-2) x
      s(-1) to 28.67 micromol CO2 X m(-2) x s(-1), and the instantaneous water use
      efficiency was from 1.39 mg x g(-1) to 3.40 mg x g(-1). Among the photosynthetic
      parameters, intercellular CO2 concentration had the smallest variable
      coefficient, while stomatal conductance had the largest one. The photosynthetic
      rate had significant conic relationships with transpiration rate and stomatal
      conductance, and had a linear relationship with intercellular CO2 concentration.
      The significant conic relationships also existed between the instantaneous water
      use efficiency and the transpiration rate and stomatal conductance. The excellent
      features of weedy rice could be used to improve the cultivated rice varieties.

PMID- 24564142
TI  - [Effects of mulching on soil moisture in a dryland winter wheat field, Northwest
      China].
AB  - This paper studied the effects of different mulching modes on the soil moisture
      in a semi-arid rainfed area of Loess Plateau, Northwest China. Seven treatments
      were installed, i. e., mulching plastic film in summer (T1), mulching plastic
      film in autumn (T2), mulching 5 cm long wheat straw in summer (T3), mulching
      whole wheat straw in summer (T4), mulching plastic film in summer plus wheat
      straw (T5), mulching used plastic film after harvest (T6), and un-mulching (CK).
      In T6, the soil moisture in different layers at different crop growth stages was
      all higher than that in CK. In the other five mulching treatments, the soil
      moisture in 0-90 cm layer before flowering stage was obviously higher, but that
      in 0-90 cm layer after flowering stage and in 90-200 cm layer during the whole
      growth season was lower than that of CK. The soil moisture in 0-200 cm layer in
      T6 during the whole growth period was significantly higher than that in CK, with
      a difference of 0.9%, but the soil moisture in 0-200 cm layer in other mulching
      treatments was lower. As compared with plastic film mulching, straw mulching
      increased the soil moisture in 0-200 cm layer. The soil moisture under mulching
      with used plastic film after harvest was higher than that under mulching with new
      plastic film. As compared to CK, the grain yield of winter wheat with plastic
      film mulching was increased by 20.3%-29.0%, and that With straw mulching was
      increased by 5.0%-16.7%. There was a significant positive correlation between the
      crop productivity and the soil water consumption during the growth period (r =
      0.77*).

PMID- 24564143
TI  - [Effects of plastic film mulching with double ridges and furrow planting on soil
      moisture and temperature and soybean yield on a semiarid dryland of Gansu
      Province, Northwest China].
AB  - Taking soybean cultivar Jindou 23 as test object, a field experiment was
      conducted at the Zhenyuan experimental station of Gansu Academy of Agricultural
      Sciences to study the effects of various plastic mulching treatments on the soil
      moisture and temperature and soybean grain yield on a semiarid dryland of
      Northwest China. Four treatments were installed, i. e., plastic film mulching
      with double ridges and furrow planting (FMRFC), plastic film mulching without
      ridges and with furrow planting (FMFC), plastic film mulching with strip planting
      (FMSC), and no mulch strip planting (NMSC, CK). During the drought year (the
      precipitation in soybean growth period was 246.3 mm) and wet year (407 mm), the
      daily soil temperature in 0-20 cm layer in all mulching treatments varied in "S"
      shape, and its fluctuation became smaller with soybean growth. The mulching
      treatments raised the daily average soil temperature in 0-20 cm layer by an
      average of 0.5-2.5 degrees C from the seedling (VE-V3) to seed filling (R6)
      stage, with the average soil temperature in whole growth period raised by 1.3-1.6
      degrees C. Both in dry year and in wet year, mulching treatments promoted the
      soil moisture consumption in 0-120 cm layer, by soybean, but increased the
      average soil moisture content and water storage in 0-200 cm layer by 1.2%-1.4%
      and 62.7-70.3 mm, respectively. As compared to CK, treatments FMRFC and FMFC had
      significant effects in improving the soil temperature and moisture environment in
      dry year, and greatly improved the yield-related traits such as plant height,
      branching number, pods per plant, and 100-seed mass. FMRFC increased the yield by
      27.7%-51.1% and raised the water use efficiency (WUE) by 47.7%- 56.3%, whereas
      FMFC increased the yield by 10.2% -25.2% and raised the WUE by 33.3%-35.4%, as
      compared to CK. It was suggested that FMRFC and FMFC could be the most efficient
      planting systems for the soybean production in the dryland farming of Northwest
      China.

PMID- 24564144
TI  - [Optimal irrigation index for cotton drip irrigation under film mulching based on
      the evaporation from pan with constant water level].
AB  - A field experiment with two irrigation cycles and two irrigating water quotas at
      squaring stage and blossoming-boll forming stage was conducted in Urumqi of
      Xinjiang Autonomous Region, Northwest China in 2008-2009, aimed to explore the
      high-efficient irrigation index of cotton drip irrigation under film mulching.
      The effects of different water treatments on the seed yield, water consumption,
      and water use efficiency (WUE) of cotton were analyzed. In all treatments, there
      was a high correlation between the cotton water use and the evaporation from pan
      installed above the plant canopy. In high-yield cotton field (including the
      treatment T4 which had 10 days and 7 days of irrigation cycle with 30.0 mm and
      37.5 mm of irrigating water quota at squaring stage and blossoming-boll forming
      stage, respectively in 2008, and the treatment T1 having 7 days of irrigation
      cycle with 22.5 mm and 37.5 mm of irrigating water quota at squaring stage and
      blossoming-boll forming stage, respectively in 2009), the pan-crop coefficient
      (Kp) at seedling stage, squaring stage, blossoming-boll forming stage, and boll
      opening stage was 0.29-0.30, 0.52-0.53, 0.74-0.88, and 0.19-0.20, respectively.
      As compared with the other treatments, T4 had the highest seed cotton yield (5060
      kg x hm(-2)) and the highest WUE (1.00 kg x m(-3)) in 2008, whereas T1 had the
      highest seed cotton yield (4467 kg x hm(-2)) and the highest WUE (0.99 kg x m(
      3)) in 2009. The averaged cumulative pan evaporation in 7 days and 10 days at
      squaring stage was 40-50 mm and 60-70 mm, respectively, and that in 7 days at
      blossoming-boll forming stage was 40-50 mm. It was suggested that in Xinjiang
      cotton area, irrigating 45 mm water for seedling emergence, no irrigation both at
      seedling stage and at boll opening stage, and irrigation was started when the pan
      evaporation reached 45-65 mm and 45 mm at squaring stage and blossoming-boll
      stage, respectively, the irrigating water quota could be determined by
      multiplying cumulative pan evaporation with Kp (the Ko was taken as 0.5, 0.75,
      0.85, and 0.75 at squaring stage, early blossoming, full-blossoming, and late
      blossoming stage, respectively), which could be the high efficient irrigation
      index to obtain high yield and WUE in drip irrigation cotton field and to save
      irrigation water resources.

PMID- 24564145
TI  - [Characteristics of soil phosphorous loss under different ecological planting
      patterns in hilly red soil regions of southern Hunan Province, China].
AB  - Taking a large standard runoff plot on a red soil slope in Qiyang County,
      southern Hunan Province as a case, this paper studied the surface soil phosphorus
      loss characteristics in the hilly red soil regions of southern Hunan under eight
      ecological planting patterns. The phosphorus loss from wasteland (T1) was most
      serious, followed by that from natural sloped cropping patterns (T2 and T3),
      while the phosphorus loss amount from terrace cropping patterns (T4-T8) was the
      least, only occupying 9.9%, 37%, 0.7%, 2.3%, and 1.9% of T1, respectively. The
      ecological planting patterns directly affected the forms of surface-lost soil
      phosphorus, with the particulate phosphorus (PP) as the main lost form. Under the
      condition of rainstorm (daily rainfall > 50 mm), rainfall had lesser effects on
      the phosphorus loss among different planting patterns. However, the phosphorus
      loss increased with increasing rain intensity. The surface soil phosphorus loss
      mainly occurred from June to September. Both the rainfall and the rain intensity
      were the factors directly affected the time distribution of surface soil
      phosphorus loss in hilly red soil regions of southern Hunan.

PMID- 24564146
TI  - [Spatial variability of soil nutirients and their relations with rice yield at
      village scale in karst mountainous area of Guizhou Province, Southwest China].
AB  - By using geo-statistics methods, an investigation was conducted on the spatial
      variability of soil pH, organic matter, total N, P, and K, and available N, P, K,
      Cu, Zn, Fe, and Mn and their relations with rice yield in Wenxing Village, Anshun
      City of Guizhou Province, Southwest China. The C0/(C0 + C) ratios for the soil
      pH, total P, and available N, P, K, and Cu and the rice yield components were
      lower than 25%, indicating their strong spatial correlations, while the C0/ (C0 +
      C) ratios for the soil organic matter, total N and K, and available Zn, Fe, and
      Mn and the rice yield were 25%-75%, showing a medium spatial correlation. Of all
      the soil nutrients, the soil available K had the closest relation with rice yield
      (r = 0.4669, P < 0.0001). The direct path coefficients of the soil available N, K
      and P to the effective panicle and thousand-grain mass were positive, in line
      with the partial correlation analysis. The Kriging interpolation showed that the
      soil organic matter, total N, and available N, K, Cu, and Zn contents presented a
      decreasing trend from the southwest to northeast, but the rice yield was higher
      in the northwest and southeast of the Wenxing Village.

PMID- 24564147
TI  - [Spatial heterogeneity of surface soil mineral components in a small catchment in
      Karst peak-cluster depression area, South China].
AB  - A total of 163 soil samples (0-20 cm layer) were collected from the grid sampling
      plots (80 m x 80 m) in Huanjiang Observation and Research Station of Karst
      Ecosystem in a small catchment in Karst cluster-peak depression area, South
      China. By using classical statistics and geostatistics, the spatial heterogeneity
      of mineral components (SiO2, Fe2O3, CaO, MgO, Al2O3, MnO, and TiO2) in the soils
      were studied. The contents of the seven soil mineral components in the study area
      differed greatly, being in the order of SiO2 > Al2O3 > CaO > MgO > Fe2O3 > TiO2 >
      MnO, and the variance coefficients also varied obviously, in the order of CaO >
      MgO > Fe2O3 > TiO2 > SiO2 > Al2O3 > MnO. The seven mineral components accounted
      for 69.4% of the total soil mass. The spatial patterns and the fittest models of
      the seven soil mineral components differed from each other. All the seven soil
      mineral components had a strong spatial autocorrelation, with shorter variation
      ranges and stronger spatial dependence. The Kriging contour maps indicated that
      the distribution patterns of soil SiO2, Fe2O3, Al2O3, MnO, and TiO2 were similar,
      being higher in south and east, lower in north and west, higher in depression,
      and lower in slope, while the distribution patterns of soil CaO and MgO were in
      adverse. Natural conditions (vegetation, bare rock rate, slope degree, and slope
      aspect, etc. ) and human disturbance were the most important factors affecting
      the spatial patterns of the soil mineral components.

PMID- 24564148
TI  - [Hyper spectral estimation method for soil alkali hydrolysable nitrogen content
      based on discrete wavelet transform and genetic algorithm in combining with
      partial least squares DWT-GA-PLS)].
AB  - Taking the Qihe County in Shandong Province of East China as the study area, soil
      samples were collected from the field, and based on the hyperspectral reflectance
      measurement of the soil samples and the transformation with the first deviation,
      the spectra were denoised and compressed by discrete wavelet transform (DWT), the
      variables for the soil alkali hydrolysable nitrogen quantitative estimation
      models were selected by genetic algorithms (GA), and the estimation models for
      the soil alkali hydrolysable nitrogen content were built by using partial least
      squares (PLS) regression. The discrete wavelet transform and genetic algorithm in
      combining with partial least squares (DWT-GA-PLS) could not only compress the
      spectrum variables and reduce the model variables, but also improve the
      quantitative estimation accuracy of soil alkali hydrolysable nitrogen content.
      Based on the 1-2 levels low frequency coefficients of discrete wavelet transform,
      and under the condition of large scale decrement of spectrum variables, the
      calibration models could achieve the higher or the same prediction accuracy as
      the soil full spectra. The model based on the second level low frequency
      coefficients had the highest precision, with the model predicting R2 being 0.85,
      the RMSE being 8.11 mg x kg(-1), and RPD being 2.53, indicating the effectiveness
      of DWT-GA-PLS method in estimating soil alkali hydrolysable nitrogen content.

PMID- 24564149
TI  - [Characteristics of seasonal drought and its adaptation in southern China under
      the background of global climate change. VI. Optimized layout of cropping system
      for preventing and avoiding drought disaster].
AB  - Southern China is an important agricultural planting region of China, but the
      seasonal drought severely impacted the regional agricultural production. Based on
      the 1981-2007 meteorological data from 13 typical meteorological stations in the
      seasonal drought areas in southern China and the data of related crops growth
      period and yield, three precipitation year types (drought year, normal year, and
      wet year) were classified based on the yearly precipitation, and by using five
      indices (coupling degree of water requirement and precipitation during crop water
      critical stages, meteorological crop yield, output value per unit area, and water
      use efficiency and precipitation during whole growth period), the comprehensive
      benefit of all possible cropping patterns in each typical region was evaluated,
      and the optimal cropping patterns in the different regions of southern China in
      different precipitation years were obtained. In the semi-arid region, the optimal
      cropping patterns in dry year included potato-maize-sweet potato and winter wheat
      rice-sweet potato. In the semi-humid region and during dry year, winter wheat
      rice-sweet potato was the best choice, and rape seed-rice-sweet potato was the
      second one. In the warm and humid region (the typical region where seasonal
      drought happened), the best cropping pattern in Jiangnan area in different
      precipitation years was potato-double cropping rice, and the suitable patterns in
      southwest area were the triple cropping systems with drought-resistant crops,
      such as winter wheat-rice-sweet potato, winter wheat-maize-sweet potato, and
      potato-double cropping rice. From the aspect of maximally utilizing water and
      heat resources, triple cropping would be the best choice, with the rice and
      upland crop rotation as the main and with the rice arranged in pairs in wet year.

PMID- 24564150
TI  - [Simulation of leaf inclination angle distribution of main tree species in
      Daxing'an Mountains of China based on the Campbell ellipsoid distribution
      function].
AB  - Leaf inclination angle distribution directly decides the amount of radiation
      interception by vegetation canopy, and also, decides the size and direction of
      the incident radiation, being the key parameter in quantitative remote sensing.
      This paper simulated the leaf inclination angle distribution of the main tree
      species in Daxing'an Mountains forest region based on the Campbell ellipsoid
      distribution model and iterative method, and quantitatively analyzed the fitting
      results of canopy with and without leaf stratification as well as the effects of
      tree age group on the leaf inclination angle distribution. For the test 6 main
      tree species, the leaf inclination angle distribution was in planophile shape,
      and the mean leaf inclination angle was smaller for coniferous tree than for
      broadleaved tree. Whether with or without stratify, the fitting result and the
      measured result were basically identical. For Betula platyphylla and Larix
      gmelinii, the correlation coefficient between the simulated and measured values
      was 0.8268 and 0.8192, and the root mean square error was 3.7% and 4.3%
      respectively, indicating that the Campbell model was reliable applied for forest
      canopy. Considering the effects of tree age group, though the leaf inclination
      angle distribution trend with leaf stratification had no correlation with age
      group, the mean leaf inclination angle of young L. gmelinii was relatively
      smaller than that mature one, suggesting that age group had positive effects on
      the numerical design of leaf inclination angle distribution and negative effects
      on the numerical design of extinction coefficient.

PMID- 24564151
TI  - [Climatic suitability model for spring maize in Northeast China].
AB  - Crop growth is a continuous and dynamic process, and thus, the optimal
      meteorological indices for crop growth also change continuously. In this paper,
      the estimation algorithms of the daily available precipitation and the temporal
      interpolation methods of meteorological indices for crop growth were developed,
      and the climatic suitability model at daily scale was established, which was
      tested by the spring maize data of agro-meteorological stations in Northeast
      China. The simulated climatic suitability had significantly positive correlations
      with the height and 100-grain mass of spring maize. The correlation coefficient
      (R2) between the climatic suitability and the spring maize height was over 0.58
      at vegetative growth stage, and over 0.45 at reproductive growth stage. The
      established climatic suitability model at daily scale could objectively reflect
      the interactions between crop growth and meteorological factors at vegetative
      growth stage and reproductive growth stage.

PMID- 24564152
TI  - [Monitoring of soil salinization in Northern Tarim Basin, Xinjiang of China in
      dry and wet seasons based on remote sensing].
AB  - Soil salinization is one of the most important eco-environment problems in arid
      area, which can not only induce land degradation, inhibit vegetation growth, but
      also impede regional agricultural production. To accurately and quickly obtain
      the information of regional saline soils by using remote sensing data is critical
      to monitor soil salinization and prevent its further development. Taking the
      Weigan-Kuqa River Delta Oasis in the northern Tarim River Basin of Xinjiang as
      test object, and based on the remote sensing data from Landsat-TM images of April
      15, 2011 and September 22, 2011, in combining with the measured data from field
      survey, this paper extracted the characteristic variables modified normalized
      difference water index (MNDWI), normalized difference vegetation index (NDVI),
      and the third principal component from K-L transformation (K-L-3). The decision
      tree method was adopted to establish the extraction models of soil salinization
      in the two key seasons (dry and wet seasons) of the study area, and the
      classification maps of soil salinization in the two seasons were drawn. The
      results showed that the decision tree method had a higher discrimination
      precision, being 87.2% in dry season and 85.3% in wet season, which was able to
      be used for effectively monitoring the dynamics of soil salinization and its
      spatial distribution, and to provide scientific basis for the comprehensive
      management of saline soils in arid area and the rational utilization of oasis
      land resources.

PMID- 24564153
TI  - [Characteristics of evapotranspiration in an alpine shrub meadow in Haibei,
      Qinghai of Northwest China].
AB  - Evapotranspiration (ET) is an important component of hydrological cycle of
      terrestrial ecosystem. To study the seasonal and interannual ET variation
      patterns of typical ecosystems is essential to better understand the water cycle
      process and to provide reference for the rational utilization of water resources.
      By using eddy covariance method, this paper studied the seasonal and interannual
      variation characteristics of ET and water budget in an alpine shrub meadow
      ecosystem in Haibei of Qinghai from 2003 to 2011. There was an obvious seasonal
      variation of ET in the study area in 2003-2011, with the maximum (4.4-5.7 mm x d(
      1)) in the vigorous growth season (July-August) and the minimum (0.09 +/- 0.04 mm
      x d(-1)) in January or December. The annual ET varied greatly among the nine
      consecutive years, being 451.3 mm in 2010 and 681.3 mm in 2007. More than 70% of
      the annual ET occurred in the growth season from May to September. The average
      ratio of annual ET to annual precipitation was 1.06 +/- 0.17, indicating that the
      water budget of this ecosystem was nearly balanced at year scale, and almost all
      the precipitation was released into atmosphere by ET.

PMID- 24564154
TI  - [Area changes of emergent herbaceous wetlands in relation to water level in East
      Dongting Lake, China in 1989-2011].
AB  - Based on multi-temporal Landsat MSS/TM/ETM+ images, and by using decision tree
      method, this paper extracted the areas of emergent herbaceous wetlands with
      different water levels in 1989-2011 in the East Dongting Lake, China. The change
      characteristics and change trends of the emergent herbaceous wetlands areas were
      investigated based on the DEM data and the daily water level data from the
      Chenglingji Hydrological Station. The area of the emergent herbaceous wetlands
      was significantly affected by water level (R2 = 0.875, P < 0.001), presenting a
      significant linear relationship between the two. Moreover, the emergent
      herbaceous wetlands area decreased with increasing water level. The higher the
      water level, the smaller the effects of the water level on the emergent area
      were. The emergent area changed regularly with water level. In January-July,
      water level increased, and the emergent area decreased; in July-December, it was
      opposite. In 1989-2011, the areas of emergent herbaceous wetlands had a continual
      increase. The newly emergent herbaceous wetlands area was mainly transformed from
      mudflat. The emergent herbaceous wetlands expansion was the co-effects of the
      increase of the emergent herbaceous wetlands areas at different elevations, and
      the rapid expansion of the emergent herbaceous wetlands in low bottomland (22-25
      m of Yellow Sea elevation) played the most important role in the expansion. The
      change of water level at different elevations was the dominant cause for the
      changes of emergent herbaceous wetlands areas in the East Dongting Lake in the
      past 20 years.

PMID- 24564155
TI  - [Polypore diversity in main natural larch forests in China].
AB  - Larch is the important coniferous species in Northern China. Many polypore
      species are growing on the fallen trunks of natural larch forests, which can
      decompose the cellulose, semi cellulose, and lignin of the fallen trunks, and
      promote the matter cycling and maintain the carbon balance in forest ecosystem,
      playing a key ecological function in forest ecosystem. Aiming at the polypore
      species on the 5 main larch forest species in China, this paper analyzed the
      species composition and distribution characteristics of polypore, and compared
      the polypore species diversity on different kinds of larch in China. A total of
      107 polypore species were recorded, belonging to 43 genera in 11 families, among
      which, brown fungi accounted for 45.4% of the total collected in this study, and
      occupied about 50% of the whole brown fungi reported in China. 91. 7% of the
      polypore grew on the decaying fallen trunk. Larix gmelini had more polypore
      species and individuals, as compared with the other 4 larch species. There was a
      high similarity in the polypore community composition on L. gmelini and L.
      olgensisi and on L. sibirica and L. griffithiana, which was in accordance with
      the natural distribution of related forests.

PMID- 24564156
TI  - [Effects of irrigation with mine wastewater on physiological characters and heavy
      metals accumulation of winter wheat].
AB  - A pot experiment was conducted to study the effects of irrigation with mine
      wastewater on the physiological characters and heavy metals accumulation of
      winter wheat. Three treatments were installed, i. e., irrigation with coal
      washing wastewater (T1), irrigation with coal-washing wastewater after its
      precipitation (T2), and irrigation with coal gangue leacheate (T3), taking the
      well water irrigation as the control (CK). The plants were irrigated with mine
      wastewater after the turning green stage. Irrigation with mine wastewater had
      negative effects on the winter wheat growth and grain yield. At anthesis stage,
      the leaf area, dry mass per stem, root activity, and net photosynthetic rate of
      winter wheat in treatments T1, T2, and T3 were significantly lower than those in
      CK (P < 0.05), the plant height and leaf chlorophyll content in T3 decreased
      significantly (P < 0.05), and the grain yield in T1, T2 and T3 was decreased by
      15.4%, 9.8%, and 17.8%, respectively. In addition, the heavy metals (Cr, Pb, Cu
      and Zn) contents in the grain of winter wheat under mine wastewater irrigation
      were significantly higher than those in CK, suggesting that the irrigation with
      mine wastewater could result in the heavy metals accumulation in wheat grain.

PMID- 24564157
TI  - [Nutrient spatiotemporal distribution and eutrophication process in subsidence
      waters of Huainan and Huaibei mining areas, China].
AB  - A total of eight mining subsidence waters, including five sites in Huainan
      "Panxie" Mining Areas (PXS-1, PXS-2, PXS-3, PXS-4, and PXS-5) and three sites in
      Huaibei "Zhu-Yang huang" Mining Areas (HBDH, HBZH, HBNH), were selected to study
      the nutrient temporal and spatial distribution and trophic states. Among the
      sites, three sites (PXS-1, PXS-3, and HBDH) showed higher nutrient level and
      could be classified into moderate eutrophication, whereas the other five were in
      moderate nutrient level and mild eutrophication. Overall, the nutrient level of
      Huainan mining subsidence waters was higher than that of Huaibei mining
      subsidence waters. All the test samples in the two mining areas had a higher
      ratio of nitrogen to phosphorus (N:P), being 25-117 in Huainan and 17-157 in
      Huaibei, and with a seasonal variety, the lowest in growth season. The dissolved
      inorganic phosphorus (DIP) in total phosphorous (TP) occupied a small percentage,
      being averagely 15.4% and 18.4% in Huainan and Huaibei mining areas,
      respectively. Nitrate was the main specie of dissolved inorganic nitrogen (DIN),
      with the ratio of nitrate to DIN being 74% and 89% in Huainan and Huaibei mining
      areas, respectively. Relative to the waters age, human activities could be one of
      the main factors responsible for the high nutrient level and the faster
      eutrophication process of these waters.

PMID- 24564158
TI  - [Spatiotemporal variation and related affecting factors of Gloiopeltis furcata
      biomass and length around Xiaoheishan Island, Shandong of China].
AB  - Gloiopeltis furcata, an important economic red macroalga, has been severely
      depleted due to human disturbances. Taking the natural G. furcata populations
      around the Xiaoheishan Island of Shandong, China as test objects, this paper
      studied the spatiotemporal variation pattern of their biomass and length and
      related affecting factors. The two-way ANCOVA showed that at island scale, both
      the subbottom and the Baardseth index had significant effects on the G. furcata
      biomass and length. The steady subbottom and the high Baardseth index were
      beneficial to the G. furcata growth. At micerohabitat scale, wave action and
      tidal level had significant effects on the G. furcata biomass and length. Wave
      wash and moderate tidal level promoted the G. furcata growth. The one-way
      repeated measurements ANOVA showed there existed seasonal variation of G. furcat
      biomass and length. The optimal growth period of G. furcata was from March to
      April, with the peak values of biomass and length appeared in late spring and
      early summer.

PMID- 24564159
TI  - [Optimal feeding strategy for juvenile Hucho taimen].
AB  - Three experiments including starvation and re-feeding, starvation and re-feeding
      recovery, and feeding frequency per day were conducted to approach the optimal
      feeding strategy for the growth and survival of juvenile Hucho taimen. In the
      experiment of starvation and re-feeding, all groups of restricted feeding showed
      non-compensatory growth. However, in the experiment of starvation and re-feeding
      recovery, different degrees of compensatory growth appeared in different starving
      groups, among which, the half a day starvation and half a day feeding group
      (S1/2) had a weight increment approximately the same as the control, and showed
      completely compensatory growth, indicating that the S1/2 could be a useful
      feeding strategy for the juvenile H. taimen at its early growth stage with the
      body mass from 0 to 2 g and at the water temperature from 9 to 15.3 degrees C. In
      feeding frequency experiment, the group T3 (three meals per day) had the highest
      body length, body mass, specific growth rate, and relatively high food conversion
      ratio, indicating that three meals a day could be more effective for improving
      the growth performance of juvenile H. taimen at its late stage with the body mass
      from 2 to 21 g and at the water temperature from 8.8 to 15.5 degrees C.

PMID- 24564160
TI  - [Effects of venom from Sclerodermus sichuanensis Xiao on pupa of Tenebrio
      molitor].
AB  - To explore the regulatory mechanisms of parasitism of Sclerodermus sichuanensis
      on Tenebrio molitor, the methods of natural parasitism and venom injection were
      adopted to investigate the effects of the venom from S. sichuanensis on the pupa
      of T. molitor in the parasitic process. Under venom injection, the paralytic
      degree of the pupa had a positive correlation with the concentration of injected
      venom, and the number of recovered pupa had a negative correlation with the
      injected venom concentration. The T. molitor pupa was in slight and reversible
      paralysis when injected with 0.01 VRE (venom reservoir equivalent) of venom, and
      in non-reversible and complete paralysis when 0.2 VRE was injected. The pupa died
      massively and appeared a wide range of melanization when injected with soil
      bacterial suspension alone, but the melanization delayed and the mortality
      declined significantly when the mixed liquor of bacterium and venom was injected.
      The bacteriostasis of the venom on Staphylococcus aureus was significantly
      stronger than that on Escherichia coli. Within a definite range of temperature,
      the paralytic activity decreased significantly with increasing temperature, the
      bacteriostasis on S. aureus increased significantly, while that on E. coli was
      opposite. This study showed that the venom from S. sichuanensis had the effects
      of paralysis, bacteriostasis, inhibiting exuviations, and delaying melanization.

PMID- 24564161
TI  - [Estrogens determination of livestock dung based on UE-SPE-HPLC/FLD].
AB  - A method for detecting the estrogens estriol, 17beta-estradiol, ethinyl
      estradiol, and bisphenol A in livestock dung was established by the combination
      of ultrasonic extraction (UE), solid phase extraction (SPE) purification, and
      high performance liquid chromatography (HPLC) with fluorescence detector (FLD).
      The dung samples were extracted with ethyl acetate ultrasonication for 30 min,
      and purified with C18 solid phase extraction column and related solvents. The
      test four estrogens in the dung samples were isolated with Inertsil ODS-SP-C18
      reversed-phase columns (150 mm x 4.6 mm, 5 microm), and the isolated estrogens
      were detected with HPLC/FLD. The mobile phase of HPLC for the detection was
      methanol/acetonitrile/water (volume ratio of 20:30:50), with a flow rate of 0.8
      mL x min(-1). The excitation and emission wavelengths of FLD were 280 and 310 nm,
      respectively, the HPLC column temperature was 40 degrees C, and the injection
      volume was 20 microL. Good linearity (correlation coefficient greater than
      0.9995) was observed by the HPLC/FLD detection when the test four estrogens
      concentrations were in the range of 1.00-1000.00 microg x L(-1). The detection
      limit of estriol, bisphenol A, 17beta-estradiol, and ethinyl estradiol was 3.35,
      5.01, 2.13, and 1.12 microg x kg(-1), respectively. When the added estrogens
      concentrations of pig, cow, and chicken dung samples were 0.05, 0.40, and, 1.00
      microg x kg(-1), the average recovery of the four estrogens was 75.1%-91.1%,
      78.4%-117.0%, and 78.6%-97.8%, respectively, with the relatively standard
      deviations (RSD, n = 6) all less than 6%. By adopting the established SPE
      HPLC/FLD method to detect the estrogens in real pig, cow, and chicken dung
      samples from parts of the large-scale livestock raising farms in Nanjing of East
      China, the detection reproducibility was high, and the detection limit was low,
      being available and effective for the detection of the estrogens in livestock
      dung.

PMID- 24564162
TI  - [Isolation and characterization of petroleum catabolic broad-host-range plasmids
      from Shen-Fu wastewater irrigation zone].
AB  - Based on triparental mating, we isolated a total of eight broad host range (BHR)
      petroleum hydrocarbon catabolic plasmids from the soils, sediments, and
      wastewater samples in the Shen-Fu irrigation zone. The antibiotic resistance of
      the plasmids was tested, and then, the plasmids were transferred to Escherichia
      coli EC100. The plasmids carrying no antibiotic resistance were tagged by miniTn5
      transposon consisting of antibiotic resistant genes. The PCR-based
      incompatibility test revealed that the pS3-2C and pS4-6G belonged to Inc P group,
      the pS3-2G, pW22-3G, and pA15-7G belonged to Inc N group, the pS7-2G was
      identified as Inc W plasmid, and the pA23-1G and pA10-1C were placed into Inc Q
      group. By adopting the reported PCR amplification methods of petroleum
      hydrocarbon-degrading catabolic genes, the petroleum-degrading capability of
      these BHR plasmids were preliminarily analyzed. The plasmids pS3-2G, pS7-2G, pA23
      1G, pW22-3G, and pA10-1C carried aromatic ring- hydroxylating dioxygenase gene
      phdA and toluene monooxygenase gene touA; the plasmid pA15-7G carried touA and
      toluene dioxygenase gene tod; the plasmid pS3-2C carried ben, phdA, and tod;
      whereas the pS4-6G only carried ben. The host range test showed that all the
      isolated plasmids except pS3-2C could be transferred and maintained stably in the
      representative strains Agrobacterium tumefaciens C58, Cupriavidus necator JMP228,
      and E. coli EC100 of the alpha-, beta-, and gamma-Proteobacteria, respectively.

PMID- 24564163
TI  - [Effects of environmental factors on litter decomposition in arid and semi-arid
      regions: A review].
AB  - Litter decomposition is one of the important biochemical processes in arid and
      semi-arid regions, and a key component of regional nutrient turnover and carbon
      cycling, which is mainly affected by climate, litter quality, and decomposer
      community. In order to deeply understand the relationships between litter
      decomposition and environmental factors in arid and semi-arid regions, this paper
      summarized the research progress in the effects of abiotic factors (soil
      temperature, precipitation, and ultraviolet-B radiation) and biotic factors
      (litter quality, soil microbial and animal composition and community structure)
      on the litter decomposition in these regions. Among the factors, precipitation
      and ultraviolet-B radiation are considered to be the main limiting factors of
      litter decomposition. In arid and semi-arid regions, precipitation can
      significantly increase the litter decomposition rate in a short term, while the
      photo-degradation induced by ultraviolet-B radiation, due to the strong and long
      term radiation, can increase the decomposition rate of terrestrial litter. Litter
      quality, soil microbial and animal composition and community structure are mainly
      affected by the type of ecosystems in a long term. However, the affecting
      mechanisms of these environmental factors on litter decomposition are still not
      very clear. It was suggested that the future litter ecological research should be
      paid more attention to the interaction of environmental factors under climate
      change, the variations of litter decomposition at different spatial scales, and
      the establishment of litter decomposition models in relation to the synergistic
      interactions of multiple factors.

PMID- 24564164
TI  - [Effects of biochar on microbial ecology in agriculture soil: a review].
AB  - Biochar, as a new type of soil amendment, has been obtained considerable
      attention in the research field of environmental sciences worldwide. The studies
      on the effects of biochar in improving soil physical and chemical properties
      started quite earlier, and already covered the field of soil microbial ecology.
      However, most of the studies considered the soil physical and chemical properties
      and the microbial ecology separately, with less consideration of their
      interactions. This paper summarized and analyzed the interrelationships between
      the changes of soil physical and chemical properties and of soil microbial
      community after the addition of biochar. Biochar can not only improve soil pH
      value, strengthen soil water-holding capacity, increase soil organic matter
      content, but also affect soil microbial community structure, and alter the
      abundance of soil bacteria and fungi. After the addition of biochar, the soil
      environment and soil microorganisms are interacted each other, and promote the
      improvement of soil microbial ecological system together. This review was to
      provide a novel perspective for the in-depth studies of the effects of biochar on
      soil microbial ecology, and to promote the researches on the beneficial effects
      of biochar to the environment from ecological aspect. The methods to improve the
      effectiveness of biochar application were discussed, and the potential
      applications of biochar in soil bioremediation were further analyzed.

PMID- 24564165
TI  - [Application of lysosomal detection in marine pollution monitoring: research
      progress].
AB  - Lysosome is an important organelle existing in eukaryotic cells. With the
      development of the study on the structure and function of lysosome in recent
      years, lysosome is considered as a target of toxic substances on subcellular
      level, and has been widely applied abroad in marine pollution monitoring. This
      paper summarized the biological characteristics of lysosomal marker enzyme,
      lysosome-autophagy system, and lysosomal membrane, and introduced the principles
      and methods of applying lysosomal detection in marine pollution monitoring.
      Bivalve shellfish digestive gland and fish liver are the most sensitive organs
      for lysosomal detection. By adopting the lysosomal detection techniques such as
      lysosomal membrane stability (LMS) test, neutral red retention time (NRRT) assay,
      morphological measurement (MM) of lysosome, immunohistochemical (Ih) assay of
      lysosomal marker enzyme, and electron microscopy (EM), the status of marine
      pollution can be evaluated. It was suggested that the lysosome could be used as a
      biomarker for monitoring marine environmental pollution. The advantages and
      disadvantages of lysosomal detection and some problems worthy of attention were
      analyzed, and the application prospects of lysosomal detection were discussed.

PMID- 24564166
TI  - [Diversity of arbuscular mycorrhizal fungi in special habitats: a review].
AB  - Arbuscular mycorrhizal fungi (AMF) are one of the important components in
      ecosystems, which not only have the diversity in genetics, species composition,
      and function, but also have the diversity in distribution and habitat. AMF infect
      plant root, form mycorrhiza, and nourish as obligate biotroph symbiont, with
      strong ecological adaptability. They not only distribute in forest, prairie, and
      farm land, but also distribute in the special habitats with less plant species
      diversity, such as commercial greenhouse soil, saline-alkali soil, mining
      pollution land, petroleum-contaminated land, pesticide-polluted soil, desert, dry
      land, wetland, marsh, plateau, volcanic, cooler, and arctic tundra, composing a
      unique community structure and playing an important irreplaceable role in the
      physiological and ecological functions. This paper summarized the species
      diversity and mycorrhizal morphological features of AMF in special habitats,
      aimed to provide essential information for the further studies on the AMF in
      these special habitats and extreme environments.

PMID- 24564168
TI  - Fabrication of bimetallic nanostructures via aerosol-assisted electroless silver
      deposition for catalytic CO conversion.
AB  - Bimetallic nanostructures were fabricated via aerosol-assisted electroless silver
      deposition for catalytic CO conversion. An ambient spark discharge was employed
      to produce nanocatalysts, and the particles were directly deposited on a
      polytetrafluoroethylene substrate for initiating silver deposition to form Pd-Ag,
      Pt-Ag, Au-Ag bimetallic nanostructures as well as a pure Ag nanostructure.
      Kinetics and morphological evolutions in the silver deposition with different
      nanocatalysts were comparatively studied. The Pt catalyst displayed the highest
      catalytic activity for electroless silver deposition, followed by the order Pd >
      Au > Ag. Another catalytic activity of the fabricated bimetallic structures in
      the carbon monoxide conversion was further evaluated at low-temperature
      conditions. The bimetallic systems showed significantly higher catalytic activity
      than that from a pure Ag system. 

PMID- 24564167
TI  - Associations between household income, height and BMI in contemporary US
      children: infancy through early childhood.
AB  - BACKGROUND: Previous studies report positive associations between household
      income and height in childhood and negative associations between income and body
      mass index (BMI). No study has evaluated concurrent associations in early-life.
      AIM: To evaluate the association between household income and anthropometric
      development in early-life. SUBJECTS AND METHODS: The Early Childhood Longitudinal
      Study-Birth Cohort (ECLS-B) is a representative sample of US children born in
      2001 and followed from ~9 months through 5 years. A generalized linear mixed
      modelling framework estimates income associations to the levels and velocities of
      height and BMI. RESULTS: A doubling of permanent income is associated with an
      ~0.26 cm height advantage over the ages of the sample and an approximate 0.11
      cm/year faster velocity at 9 months. All race-sex sub-groups show some positive
      association between income and height. Income shows little association to BMI at
      9 months but by 5 years a doubling of income is associated with a 0.25 kg/m(2)
      lower BMI. This is suggested to derive from a lower BMI velocity associated with
      higher income. The BMI relationships are generally reflective of white and
      Hispanic children. CONCLUSION: The findings suggest that associations between
      income and anthropometric development in US children have origins in early-life.

PMID- 24564170
TI  - Regioselective and stoichiometrically controlled conjugation of photodynamic
      sensitizers to a HER2 targeting antibody fragment.
AB  - The rapidly increasing interest in the synthesis of antibody-drug conjugates as
      powerful targeted anticancer agents demonstrates the growing appreciation of the
      power of antibodies and antibody fragments as highly selective targeting
      moieties. This targeting ability is of particular interest in the area of
      photodynamic therapy, as the applicability of current clinical photosensitizers
      is limited by their relatively poor accumulation in target tissue in comparison
      to healthy tissue. Although synthesis of porphyrin-antibody conjugates has been
      previously demonstrated, existing work in this area has been hindered by the
      limitations of conventional antibody conjugation methods. This work describes the
      attachment of azide-functionalized, water-soluble porphyrins to a tratuzumab Fab
      fragment via a novel conjugation methodology. This method allows for the
      synthesis of a homogeneous product without the loss of structural stability
      associated with conventional methods of disulfide modification. Biological
      evaluation of the synthesized conjugates demonstrates excellent selectivity for a
      HER2 positive cell line over the control, with no dark toxicity observed in
      either case. 

PMID- 24564169
TI  - Computational tools for copy number variation (CNV) detection using next
      generation sequencing data: features and perspectives.
AB  - Copy number variation (CNV) is a prevalent form of critical genetic variation
      that leads to an abnormal number of copies of large genomic regions in a cell.
      Microarray-based comparative genome hybridization (arrayCGH) or genotyping arrays
      have been standard technologies to detect large regions subject to copy number
      changes in genomes until most recently high-resolution sequence data can be
      analyzed by next-generation sequencing (NGS). During the last several years, NGS
      based analysis has been widely applied to identify CNVs in both healthy and
      diseased individuals. Correspondingly, the strong demand for NGS-based CNV
      analyses has fuelled development of numerous computational methods and tools for
      CNV detection. In this article, we review the recent advances in computational
      methods pertaining to CNV detection using whole genome and whole exome sequencing
      data. Additionally, we discuss their strengths and weaknesses and suggest
      directions for future development. 

PMID- 24564171
TI  - A gene signature based method for identifying subtypes and subtype-specific
      drivers in cancer with an application to medulloblastoma.
AB  - BACKGROUND: Subtypes are widely found in cancer. They are characterized with
      different behaviors in clinical and molecular profiles, such as survival rates,
      gene signature and copy number aberrations (CNAs). While cancer is generally
      believed to have been caused by genetic aberrations, the number of such events is
      tremendous in the cancer tissue and only a small subset of them may be
      tumorigenic. On the other hand, gene expression signature of a subtype represents
      residuals of the subtype-specific cancer mechanisms. Using high-throughput data
      to link these factors to define subtype boundaries and identify subtype-specific
      drivers, is a promising yet largely unexplored topic. RESULTS: We report a
      systematic method to automate the identification of cancer subtypes and candidate
      drivers. Specifically, we propose an iterative algorithm that alternates between
      gene expression clustering and gene signature selection. We applied the method to
      datasets of the pediatric cerebellar tumor medulloblastoma (MB). The subtyping
      algorithm consistently converges on multiple datasets of medulloblastoma, and the
      converged signatures and copy number landscapes are also found to be highly
      reproducible across the datasets. Based on the identified subtypes, we developed
      a PCA-based approach for subtype-specific identification of cancer drivers. The
      top-ranked driver candidates are found to be enriched with known pathways in
      certain subtypes of MB. This might reveal new understandings for these subtypes.
      CONCLUSIONS: Our study indicates that subtype-signature defines the subtype
      boundaries, characterizes the subtype-specific processes and can be used to
      prioritize signature-related drivers.

PMID- 24564172
TI  - Do women's mate preferences change across the ovulatory cycle? A meta-analytic
      review.
AB  - Scientific interest in whether women experience changes across the ovulatory
      cycle in mating-related motivations, preferences, cognitions, and behaviors has
      surged in the past 2 decades. A prominent hypothesis in this area, the ovulatory
      shift hypothesis, posits that women experience elevated immediate sexual
      attraction on high- relative to low-fertility days of the cycle to men with
      characteristics that reflected genetic quality ancestrally. Dozens of published
      studies have aimed to test this hypothesis, with some reporting null effects. We
      conducted a meta-analysis to quantitatively evaluate support for the pattern of
      cycle shifts predicted by the ovulatory shift hypothesis in a total sample of 134
      effects from 38 published and 12 unpublished studies. Consistent with the
      hypothesis, analyses revealed robust cycle shifts that were specific to women's
      preferences for hypothesized cues of (ancestral) genetic quality (96 effects in
      50 studies). Cycle shifts were present when women evaluated men's "short-term"
      attractiveness and absent when women evaluated men's "long-term" attractiveness.
      More focused analyses identified specific characteristics for which cycle shifts
      were or were not robust and revealed areas in need of more research. Finally, we
      used several methods to assess potential bias due to an underrepresentation of
      small effects in the meta-analysis sample or to "researcher degrees of freedom"
      in definitions of high- and low-fertility cycle phases. Neither type of bias
      appeared to account for the observed cycle shifts. The existence of robust
      relationship context-dependent cycle shifts in women's mate preferences has
      implications for understanding the role of evolved psychological mechanisms and
      the ovulatory cycle in women's attractions and social behavior.

PMID- 24564175
TI  - Methodological concerns for meta-analyses of meditation: Comment on Sedlmeier et
      al. (2012).
AB  - We commend Sedlmeier et al. (2012) for their significant undertaking of meta
      analysis of all meditation types on all psychological variables, but additional
      analyses may modify some of their conclusions. Whereas they suggest from visual
      inspection of funnel diagrams that there may be publication bias of
      underreporting low-effect studies on the Transcendental Meditation (TM)
      technique, quantitative tests do not indicate the presence of bias for any type
      of meditation. We additionally found that there was no significant difference in
      effect sizes between studies originating from researchers affiliated with a TM
      organization and studies from other universities. We found that comparison of
      different types of meditation on their global index was confounded because their
      global index aggregated different sets of variables for the different groups.
      That is, using composite indices that only aggregated variables for which each
      group had at least 3 studies confirmed the authors' conclusion that effect sizes
      for different research designs were not different, but found that effect sizes
      for the TM technique were significantly larger than effect sizes for mindfulness
      meditation or other meditations. We also located 35 studies on the TM technique
      that appear to meet the authors' inclusion criteria that were missed by their
      meta-analysis, and several others on important psychosocial behavioral variables,
      such as job performance, substance abuse, and prison recidivism that were not
      reviewed. In addition, we suggest that future meta-analyses on psychological
      variables include cross-validating physiological studies.

PMID- 24564176
TI  - Meta-analyses and other methodological issues in meditation research: Reply to
      Orme-Johnson and Dillbeck (2014).
AB  - We are grateful to Orme-Johnson and Dillbeck (2014) for raising several potential
      methodological concerns they have with our meta-analysis of the psychological
      effects of meditation and for thereby providing us with the opportunity to
      clarify these points. Orme-Johnson and Dillbeck raised 4 points that they
      believed might have led to unfair treatment of studies that reported the effects
      of transcendental meditation (TM). First, they were concerned with the way we
      aggregated effects over different categories of variables. Second, they disagreed
      with our contention that there might have been some upward bias in the effects
      reported for TM studies. Third, they argued that the results from TM studies do
      not differ depending on whether studies were done by researchers affiliated with
      TM institutions, and 4th, they questioned the completeness of our selection of TM
      studies. We still believe that our methodology for reporting study results was
      justified on theoretical grounds and argue that the results for all variable
      categories are readily available in our analysis. We also still find some
      indication of upward bias for TM studies, even using the method they propose. We
      cannot say much regarding author affiliation because we did not raise that point,
      and, last, we have to concede that we indeed missed some TM studies. Yet this
      omission did not have any substantial practical consequences concerning our
      conclusions. We end with a short discussion about how meditation research should
      be conducted in the future.

PMID- 24564177
TI  - Carboxymethylcellulose-based and docetaxel-loaded nanoparticles circumvent P
      glycoprotein-mediated multidrug resistance.
AB  - Taxanes are a class of anticancer agents with a broad spectrum and have been
      widely used to treat a variety of cancer. However, its long-term use has been
      hampered by accumulating toxicity and development of drug resistance. The most
      extensively reported mechanism of resistance is the overexpression of P
      glycoprotein (Pgp). We have developed a PEGylated carboxymethylcellulose
      conjugate of docetaxel (Cellax), which condenses into ~120 nm nanoparticles. Here
      we demonstrated that Cellax therapy did not upregulate Pgp expression in MDA-MB
      231 and EMT-6 breast tumor cells, whereas a significant increase in Pgp
      expression was measured with native docetaxel (DTX) treatment. Treatment with DTX
      led to 4-7-fold higher Pgp mRNA expression and 2-fold higher Pgp protein
      expression compared with Cellax treatment in the in vitro and in vivo system,
      respectively. Cellax also exhibited significantly increased efficacy compared
      with that of DTX in a taxane-resistant breast tumor model. Against the highly Pgp
      expressing EMT6/AR1 cells, Cellax exhibited a 6.5 times lower IC50 compared with
      that of native DTX, and in the in vivo model, Cellax exhibited 90% tumor growth
      inhibition, while native DTX had no significant antitumor activity. 

PMID- 24564179
TI  - Mining nutrients (N, K, P) from urban source-separated urine by forward osmosis
      dewatering.
AB  - Separating urine from domestic wastewater promotes a more sustainable municipal
      wastewater treatment system. This study investigated the feasibility of applying
      a forward osmosis (FO) dewatering process for nutrient recovery from source
      separated urine under different conditions, using seawater or desalination brine
      as a low-cost draw solution. The filtration process with the active layer facing
      feed solution exhibited relatively high water fluxes up to 20 L/m(2)-h. The
      process also revealed relatively low rejection to neutral organic nitrogen (urea
      N) in fresh urine but improved rejection of ammonium (50-80%) in hydrolyzed urine
      and high rejection (>90%) of phosphate, potassium in most cases. Compared to
      simulation based on the solution-diffusion mechanism, higher water flux and
      solute flux were obtained using fresh or hydrolyzed urine as the feed, which was
      attributed to the intensive forward nutrient permeation (i.e., of urea, ammonium,
      and potassium). Membrane fouling could be avoided by prior removal of the
      spontaneously precipitated crystals in urine. Compared to other urine treatment
      options, the current process was cost-effective and environmentally friendly for
      nutrient recovery from urban wastewater at source, yet a comprehensive life-cycle
      impact assessment might be needed to evaluate and optimize the overall system
      performance at pilot and full scale operation. 

PMID- 24564180
TI  - Reactions of amino acids, peptides, and proteins with oxidized metabolites of
      tris(p-carboxyltetrathiaaryl)methyl radical EPR probes.
AB  - Oxidation of the tris(p-carboxyltetrathiaaryl)methyl (TAM) EPR radical probe,
      TAMa(*), by rat liver microsomes (RLM) + NADPH, or horseradish peroxidase (HRP) +
      H2O2, or K2IrCl6, led to an intermediate cation, TAMa(+), which was treated with
      glutathione (GSH), with formation of an adduct, TAMa-SG(*), resulting from the
      substitution of a TAMa(*) carboxylate group with the SG group. L-alpha-Amino
      acids containing a strong nucleophilic residue (NuH), such as L-cysteine or L
      histidine, also reacted with TAMa(+), with formation of radical adducts TAMa
      Nu(*) in which a carboxylate group of TAMa(*) was replaced with Nu. Other less
      nucleophilic L-alpha-amino acids, such as L-arginine, L-serine, L-threonine, L
      tyrosine, or L-aspartate, as well as the tetrapeptide H-(Gly)4-OH, reacted with
      TAMa(+) via their alpha-NH2 group, with formation of an iminoquinone methide,
      IQMa, deriving from an oxidative decarboxylation and amination of TAMa(*). Upon
      reaction of TAMa(+) with L-proline and L-lysine, N-substituted iminoquinone
      methide adducts, IQMa-Pro and IQMa-Lys, were formed. Finally, preliminary results
      showed that oxidation of TAMa(*) in the presence of bovine serum albumin (BSA),
      led to the covalent binding of TAMa-derived metabolites to BSA. Oxidation of
      another frequently used TAM probe, TAMb(*) (Oxo63), in the presence of GSH, N
      acetyl-cysteine methyl ester, or histidine also led to TAMb-Nu(*) adducts
      equivalent to the corresponding TAMa-Nu(*) adducts, suggesting that the oxidative
      metabolism of such TAM(*) probes could lead to protein covalent binding.
      Moreover, the above data describe an easy access to new TAM radical EPR probes
      coupled to amino acids, peptides or proteins that could be useful for addressing
      various biological targets.

PMID- 24564178
TI  - C-reactive protein levels in patients at cardiovascular risk: EURIKA study.
AB  - BACKGROUND: Elevated C-reactive protein (CRP) levels are associated with high
      cardiovascular risk, and might identify patients who could benefit from more
      carefully adapted risk factor management. We have assessed the prevalence of
      elevated CRP levels in patients with one or more traditional cardiovascular risk
      factors. METHODS: Data were analysed from the European Study on Cardiovascular
      Risk Prevention and Management in Usual Daily Practice (EURIKA,
      ClinicalTrials.gov Identifier: NCT00882336), which included patients (aged >=50
      years) from 12 European countries with at least one traditional cardiovascular
      risk factor but no history of cardiovascular disease. Analysis was also carried
      out on the subset of patients without diabetes mellitus who were not receiving
      statin therapy. RESULTS: In the overall population, CRP levels were positively
      correlated with body mass index and glycated haemoglobin levels, and were
      negatively correlated with high-density lipoprotein cholesterol levels. CRP
      levels were also higher in women, those at higher traditionally estimated
      cardiovascular risk and those with greater numbers of metabolic syndrome markers.
      Among patients without diabetes mellitus who were not receiving statin therapy,
      approximately 30% had CRP levels >=3 mg/L, and approximately 50% had CRP levels
      >=2 mg/L, including those at intermediate levels of traditionally estimated
      cardiovascular risk. CONCLUSIONS: CRP levels are elevated in a large proportion
      of patients with at least one cardiovascular risk factor, without diabetes
      mellitus who are not receiving statin therapy, suggesting a higher level of
      cardiovascular risk than predicted according to conventional risk estimation
      systems. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00882336.

PMID- 24564181
TI  - Power-dependent Raman analysis of highly strained Si nanobridges.
AB  - Strain analysis of complex three-dimensional nanobridges conducted via Raman
      spectroscopy requires careful experimentation and data analysis supported by
      simulations. A method combining micro-Raman spectroscopy with finite element
      analysis is presented, enabling a detailed understanding of strain-sensitive
      Raman data measured on Si nanobridges. Power-dependent measurements are required
      to account for the a priori unknown scattering efficiency related to size and
      geometry. The experimental data is used to assess the validity of previously
      published phonon deformation potentials. 

PMID- 24564182
TI  - On the inversion-indel distance.
AB  - BACKGROUND: The inversion distance, that is the distance between two
      unichromosomal genomes with the same content allowing only inversions of DNA
      segments, can be computed thanks to a pioneering approach of Hannenhalli and
      Pevzner in 1995. In 2000, El-Mabrouk extended the inversion model to allow the
      comparison of unichromosomal genomes with unequal contents, thus insertions and
      deletions of DNA segments besides inversions. However, an exact algorithm was
      presented only for the case in which we have insertions alone and no deletion (or
      vice versa), while a heuristic was provided for the symmetric case, that allows
      both insertions and deletions and is called the inversion-indel distance. In
      2005, Yancopoulos, Attie and Friedberg started a new branch of research by
      introducing the generic double cut and join (DCJ) operation, that can represent
      several genome rearrangements (including inversions). Among others, the DCJ model
      gave rise to two important results. First, it has been shown that the inversion
      distance can be computed in a simpler way with the help of the DCJ operation.
      Second, the DCJ operation originated the DCJ-indel distance, that allows the
      comparison of genomes with unequal contents, considering DCJ, insertions and
      deletions, and can be computed in linear time. RESULTS: In the present work we
      put these two results together to solve an open problem, showing that, when the
      graph that represents the relation between the two compared genomes has no bad
      components, the inversion-indel distance is equal to the DCJ-indel distance. We
      also give a lower and an upper bound for the inversion-indel distance in the
      presence of bad components.

PMID- 24564183
TI  - Wnt3a expression is associated with MMP-9 expression in primary tumor and
      metastatic site in recurrent or stage IV colorectal cancer.
AB  - BACKGROUND: The wnt/beta-catenin signaling pathway is known to affect in cancer
      oncogenesis and progression by interacting with the tumor microenvironment.
      However, the roles of wnt3a and wnt5a in colorectal cancer (CRC) have not been
      thoroughly studied. In the present study, we investigated the expression of wnt
      protein and the concordance rate in primary tumor and metastatic sites in CRC. To
      determine the relationship of wnt proteins with invasion related protein, we also
      analyzed the association between wnt protein expression and the expression of
      matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor
      receptor-2 (VEGFR-2). METHODS: Tumor tissue was obtained from eighty-three
      paraffin- embedded blocks which were using resected tissue from both the primary
      tumor and metastatic sites for each patient. We performed immunohistochemical
      staining for wnt3a, wnt5a, beta-catenin, MMP-9 and VEGFR-2. RESULTS: Wnt3a,
      wnt5a, beta-catenin, and MMP-9 expression was high; the proteins were found in
      over 50% of the primary tumors, but the prevalence was lower in tissue from
      metastatic sites. The concordance rates between the primary tumor and metastatic
      site were 76.2% for wnt5a and 79.4% for wnt3a and beta-catenin, but VEGFR-2 was
      expressed in 67.4% of the metastatic sites even when not found in the primary
      tumor. Wnt3a expression in primary tumors was significantly associated with lymph
      node involvement (p = 0.038) and MMP-9 expression in the primary tumor (p =
      0.0387), mesenchyme adjacent to tumor (p = 0.022) and metastatic site (p =
      0.004). There was no other relationship in the expression of these proteins.
      Vascular invasion in primary tumor tissue may be a potential prognostic marker
      for liver metastasis, but no significant association was observed among the wnt
      protein, MMP-9, and VEGFR-2 for peritoneal seeding. In survival analysis, beta
      catenin expression was significantly correlated with overall survival (p = 0.05).
      CONCLUSIONS: Wnt3a and wnt5a expression had a concordance rate higher than 60%
      with a high concordance rate between the primary tumor and metastatic site. Wnt3a
      expression is associated with the expression of MMP-9 in primary tumor tissue
      adjacent mesenchymal tissue, and at the metastatic site. As a prognostic marker,
      only beta-catenin expression showed significant relation with survival outcome.

PMID- 24564185
TI  - Effects of phonological awareness and naming speed on mathematics skills in
      children with mild intellectual disabilities.
AB  - OBJECTIVE: Both phonological awareness (PA) and naming speed have been identified
      as two skills related to the development of mathematics skills for children with
      and without learning disabilities. The purpose of the present study was to
      investigate the relationships between PA and colour naming speed for 265
      elementary school students with mild intellectual disabilities (MID). METHODS:
      Participants were assessed using the Comprehensive Test of Phonological Processes
      and the KeyMath Revised Diagnostic Inventory of Essential Mathematics. RESULTS:
      Hierarchical regression analyses accounting for the effects of age indicated that
      children with MID rely on both PA and naming speed when solving mathematics
      problems, although PA was the more robust indicator of the two. CONCLUSION: As a
      whole, these results suggest that children with intellectual disabilities
      evidence the same types of reading and math relationships as shown for other
      populations of children.

PMID- 24564184
TI  - Rapamycin promoted thrombosis and platelet adhesion to endothelial cells by
      inducing membrane remodeling.
AB  - BACKGROUND: Recently, evidence indicated that the rapamycin-eluting stent which
      was used worldwide may contribute to an increased risk for thrombosis. On the
      contrary, other researchers found it was safe. Thus, it is necessary to clarify
      the effect of rapamycin on thrombosis and the corresponding mechanisms. RESULTS:
      The effects of rapamycin in vivo were evaluated by modified deep vein thrombosis
      animal model. The platelets were from healthy volunteers and the platelet
      endothelium (purchased from ATCC) adhesion in cultured endothelial cells was
      assessed. Membrane rufflings in endothelial cells were examined by confocal and
      electron microscope. Thrombus formation increased in rats that were injected with
      rapamycin. Electron microscope analysis exhibited microvilli on the rapamycin
      treated endothelium in rats. Rapamycin enhanced membrane ruffling in human
      umbilical vein endothelial cells (HUVECs) and adhesion of platelets to HUVECs.
      The platelet-HUVECs adhesion was attenuated when cells were treated with
      cytochalacin B. Inhibition of autophagy by 3-methyladenine led to suppression of
      membrane ruffles in HUVECs and augmentation of platelet-endothelial adhesion.
      CONCLUSIONS: In conclusion, we found that endothelial membrane remodeling induced
      by rapamycin is crucial for the adhesion of platelets to endothelial cells and
      thereby for thrombosis in vivo, and that the endothelial membrane remodeling is
      autophagy dependent.

PMID- 24564187
TI  - Delayed gait disturbance due to injury of the corticoreticular pathway in a
      patient with mild traumatic brain injury.
AB  - BACKGROUND: Many studies have demonstrated neural injury in patients with mild
      traumatic brain injury, using diffusion tensor imaging (DTI). However, knowledge
      regarding injury of the corticoreticular pathway (CRP) is limited. This study
      reports on a patient with mild TBI who showed delayed gait disturbance due to
      injury of the CRP following head trauma, which was demonstrated by DTI. METHODS:
      A 14-year-old female patient suffered from an in-car accident: her head was hit
      with the backseat during hyperextension after flexion movement when her sedan was
      struck by another sedan from behind. She showed mild quadriparesis after onset.
      At 29 days after onset, she noted gait disturbance and aggravated quadriparesis
      with more severe weakness of the proximal joints. RESULTS: No abnormality was
      observed on brain MRI and electromyography study performed at 10 weeks after
      onset. Both CRPs were discontinued at the midbrain level on 10-week DTI.
      CONCLUSION: It appears that the proximal weakness of this patient was attributed
      to injury of both CRPs following head trauma. It is assumed that the mild
      weakness at the onset of head trauma was caused by the primary traumatic axonal
      injury and the aggravated weakness that started from 29 days might be ascribed to
      the secondary traumatic axonal injury.

PMID- 24564189
TI  - Changing food patterns across the seasons in rural Pakistan: analysis of food
      variety, dietary diversity and calorie intake.
AB  - This comparative study investigated variations in food patterns across the
      seasons in rural Pakistan through assessing the changes in food variety, dietary
      diversity and calorie intake. It analyzed the situation using the primary
      information of 97 and 114 households surveyed in summer and winter respectively.
      Findings revealed a significant difference of households' food variety, dietary
      diversity and calorie intake across the seasons. In the winter, households' food
      basket was more diverse, showing 30%, 13%, and 8% rise in food variety, dietary
      diversity, and caloric intake, respectively, due mainly to the changes in food
      choices in winter. Rural households preferred to consume items from nutritious
      food groups (i.e., dried fruits and nuts, oilseeds, and locally preserved foods)
      during the severe cold weather. However, they did not substitute significantly
      the items from basic food groups (i.e., cereals, vegetables and legumes, tubers,
      and dairy products), with those belonging to nutritious groups. Based on
      findings, it is concluded that food variety, dietary diversity and calorie intake
      fluctuate across the seasons, therefore surveys of dietary patterns and calorie
      intake in one particular season may not be reliable, and food security status of
      households may not be generalized on the basis of one season survey. 

PMID- 24564186
TI  - Improving reliability and absolute quantification of human brain microarray data
      by filtering and scaling probes using RNA-Seq.
AB  - BACKGROUND: High-throughput sequencing is gradually replacing microarrays as the
      preferred method for studying mRNA expression levels, providing nucleotide
      resolution and accurately measuring absolute expression levels of almost any
      transcript, known or novel. However, existing microarray data from clinical,
      pharmaceutical, and academic settings represent valuable and often
      underappreciated resources, and methods for assessing and improving the quality
      of these data are lacking. RESULTS: To quantitatively assess the quality of
      microarray probes, we directly compare RNA-Seq to Agilent microarrays by
      processing 231 unique samples from the Allen Human Brain Atlas using RNA-Seq.
      Both techniques provide highly consistent, highly reproducible gene expression
      measurements in adult human brain, with RNA-Seq slightly outperforming microarray
      results overall. We show that RNA-Seq can be used as ground truth to assess the
      reliability of most microarray probes, remove probes with off-target effects, and
      scale probe intensities to match the expression levels identified by RNA-Seq.
      These sequencing scaled microarray intensities (SSMIs) provide more reliable,
      quantitative estimates of absolute expression levels for many genes when compared
      with unscaled intensities. Finally, we validate this result in two human cell
      lines, showing that linear scaling factors can be applied across experiments
      using the same microarray platform. CONCLUSIONS: Microarrays provide consistent,
      reproducible gene expression measurements, which are improved using RNA-Seq as
      ground truth. We expect that our strategy could be used to improve probe quality
      for many data sets from major existing repositories.

PMID- 24564190
TI  - The absence of wild game and fish species from the USDA National Nutrient
      Database for standard reference: addressing information gaps in wild caught
      foods.
AB  - We highlighted gaps in nutritional data for wild game meat and wild caught fish
      that have a regulated harvesting season in New York State, and examined the
      possible role that wild game and fish play in current trends towards consumption
      of local, healthy meat sources. This project is part of larger study that
      examines family food decision-making, and explores possibilities for leveraging
      the locavore movement in support of consumption of wild game and fish. 

PMID- 24564188
TI  - The effect of Haemophilus influenzae type B and pneumococcal conjugate vaccines
      on childhood meningitis mortality: a systematic review.
AB  - BACKGROUND: Two of the most prevalent causes of severe bacterial meningitis in
      children, Haemophilus influenzae type B (Hib) and Streptococcus pneumoniae, are
      preventable by existing vaccines increasingly available in developing countries.
      Our objective was to estimate the dose-specific effect of Hib and pneumococcal
      conjugate vaccines (PCV) on childhood meningitis mortality in low-income
      countries for use in the Lives Saved Tool (LiST). METHODS: We systematically
      searched and reviewed published vaccine efficacy trials and observational studies
      reporting the effect of Hib or PCV vaccines on organism-specific meningitis,
      bacterial meningitis and all-cause meningitis incidence and mortality among
      children less than five years old in low- and middle-income countries. Data
      collection and quality assessments were performed using standardized guidelines.
      For outcomes available across multiple studies (>= 2) and approximating
      meningitis mortality, we pooled estimates reporting dose-specific effects using
      random effects meta-analytic methods, then combined these with meningitis
      etiology data to determine the preventable fraction of childhood meningitis
      mortality for inclusion in LiST. RESULTS: We identified 18 studies of Hib
      conjugate vaccines reporting relevant meningitis morbidity and mortality outcomes
      (2 randomized controlled trials [RCTs], 16 observational studies) but few
      provided dose-specific effects. A meta-analysis of four case-control studies
      examined the dose-specific effect of Hib conjugate vaccines on Hib meningitis
      morbidity (1 dose: RR=0.64, 95% CI 0.38-1.06; 2 doses: RR=0.09, 95% CI 0.03-0.27;
      3 doses: RR=0.06, 95% CI 0.02-0.22), consistent with results from single RCTs.
      Pooled estimates of two RCTs provided evidence for the effect of three doses of
      PCV on vaccine-serotype meningitis morbidity (RR=0.16, 95% CI 0.02-1.20). We
      considered these outcomes of severe disease as proxy estimates for meningitis
      mortality and combined the estimates of protective effects with meningitis
      etiology data to provide an estimate of the preventable fraction of childhood
      meningitis mortality with three doses of Hib (38-43%) and pneumococcal conjugate
      vaccines (28-35%) for use in LiST. CONCLUSIONS: Few RCTs or vaccine effectiveness
      studies evaluated the dose-specific impact of Hib and PCV vaccines on childhood
      meningitis mortality, necessitating use of proxy measures to estimate population
      impact in LiST. Our analysis indicates that approximately three-quarters of
      meningitis deaths are preventable with existing Hib and PCV vaccines.

PMID- 24564191
TI  - "It's like big mama's house": examining extended family influences on the dietary
      behaviors of African American children.
AB  - The family environment plays an important role in influencing children's dietary
      behaviors. Traditionally, African American extended family members play a key
      role in child socialization. We examine the role of extended families in how
      children are socialized to adopt dietary norms. We conducted in-depth, semi
      structured interviews with 24 individuals across eight family units to elicit
      information regarding the influences of culture and families on children's
      dietary behaviors. Findings suggest that families teach children to value
      activities that combine quality time and enjoying food together; adults are
      inconsistent in how they teach children to adopt desired dietary behaviors. This
      work has implications for improving family-based interventions for African
      American children through promoting healthful behaviors that are also respectful
      of family dietary traditions, improving communication between adults and
      children, and leveraging family members as attitudinal and behavioral referents. 

PMID- 24564192
TI  - Consumption habits and innovation potential of mung bean foods in Hisar District
      of Haryana State, India.
AB  - Consumption habits for mung bean foods were assessed by the free word association
      method and interview techniques. Four groups of closely related products and
      perceived quality were revealed. The largest group comprised sweets and snacks,
      which were associated with unhealthiness, expensiveness and sensory liking.
      Another group consisted of split dhals associated with convenience and
      healthiness. It appeared that under different circumstances food choices vary and
      are influenced more by socioeconomic restrictions then by consumer perception and
      preferences. Scenario analysis based on consumer perception, preferences,
      practices and nutritional value of products revealed dhals as the most promising
      food for innovation. 

PMID- 24564193
TI  - Measuring household food security using food intake indicators in rural Kwazulu
      Natal, South Africa.
AB  - Estimation of micronutrients intake in food consumption surveys has generally
      been ignored. Focusing on similar households, a household food consumption survey
      (n = 200) was carried out in November 2004 (period of less) and March 2005
      (period of plenty) in rural KwaZulu Natal, South Africa. Diet diversity, energy,
      protein and micronutrient intakes were proxies of household food security.
      Principal Component Analysis was used to estimate household food adequacy and
      strength of the variables (nutrients) in determining household intake variation
      amongst the community. On average, variation in household intake was contributed
      by energy (62.8%), iron (20.2%), protein (11.8%), vitamin E (3.8%), vitamin A
      (1.0%), and dietary diversity (0.3%). Linking food intake to household variables
      can generate plausible variables for measuring household food security. 

PMID- 24564194
TI  - Coping with food insecurity on a micro-scale: evidence from Ethiopian rural
      households.
AB  - This article examines the main household demographics and economic factors
      associated with food insecurity and coping behavior of rural households employed
      during times of food shortages in northern Ethiopia. Using a cost-of-basic-needs
      approach we estimated the food poverty line. This cut-off value was used to
      classify households as either food secure or insecure. Then empirical analyses
      were used, based on respectively a logit regression model and a coping strategy
      index. The estimated results revealed that household size, size of farm land,
      livestock ownership, frequency of extension services, and proximity to basic
      infrastructures are associated with the food security status of farming
      households in the study area. Moreover, households relied largely on consumption
      based coping strategies when faced with food shortages. 

PMID- 24564195
TI  - Synthesis, characterization, and catalytic properties of cationic hydrogels
      containing copper(II) and cobalt(II) ions.
AB  - Here, we report the synthesis and characterization of a hydrogel based on
      ethylene glycol diglycidyl ether (EGDE) and 1,8-diamino-3,6-dioxaoctane (DA).
      Chemically stable Co(II) and Cu(II) coordination complexes were prepared with
      this nonsoluble polyelectrolyte, poly(EGDE-DA), and studied by ss-NMR, FT-IR,
      thermogravimetry, and microscopy. Mesopores were found in all the samples, the
      thermal stability of the polymer matrix was highly affected by the presence of
      metal ions, and the (13)C CP-MAS spectrum for the Cu(II)-complex evidenced a
      significant increase in the reticulation degree by Cu(II) ions. The catalytic
      activity of these materials on H2O2 activation was studied by electron spin
      resonance (ESR). The Co(II)-poly(EGDE-DA)/H2O2 heterogeneous system produced O2,
      an anion superoxide (O2(*)-), and a hydroxyl radical (OH(*)), which diffused into
      the solution at the time that a decrease in pH was detected. In the same way, the
      Cu(II)-poly(EGDE-DA)/H2O2 heterogeneous system produced O2 and OH(*). H2O2
      activation by the poly(EGDE-DA) complexes with Co(II) and Cu(II) were applied on
      the decolorization of solutions of the azo-dye methyl orange (MO). In the
      presence of 63 mM H2O2, 87% of MO was removed in 10 min with Cu(II)-poly(EGDE-DA)
      and in 110 min with Co(II)-poly(EGDE-DA). In addition, the pharmaceutical product
      epinephrine was partially oxidized to adrenochrome by the O2(*)- released from
      the Co(II)-poly(EGDE-DA)/H2O2 heterogeneous system. 

PMID- 24564197
TI  - Stimulation of Cellulases by Small Phenolic Compounds in Pretreated Stover.
AB  - The effect of small phenolic compounds in pretreated stover on celluase activity
      is crucial but has not yet been fully elucidated. This work investigated the
      effects of both phenolic acid and phenolic aldehyde on cellulase activity. The
      model substances of small phenolic compounds identified in steam exploded corn
      stover were used to examine their individual effects on cellulase activity. It
      was found that phenolic aldehyde significantly inhibited cellulase activity at
      0.05-8 g/L. However, phenolic acids might have a concentration-dependent effect
      on cellulase activity: significant inhibition at 0.05 g/L and slight stimulation
      at 2-4 g/L. Small phenolic compounds mixture might also have a concentration
      dependent effect on cellulase activity: significant stimulation at 2-8 g/L and
      slight inhibition at 0.05-1 g/L. The small phenolic compounds in pretreated
      stover were proven to be able to significantly stimulate enzymatic hydrolysis of
      stover. On the basis of these results, it is proposed that the concentration
      dependent effects of small phenolic compounds on cellulase activity should be
      considered while removing them after pretreatment.

PMID- 24564196
TI  - Interleukin-10 gene polymorphisms in recurrent aphthous stomatitis.
AB  - Recurrent aphthous stomatitis (RAS) is a common oral inflammatory disease with
      unknown etiology in which the immune system seems to have a role in oral
      tolerance. Interleukin (IL)-10 is a cytokine synthesis inhibitory factor. Single
      nucleotide polymorphisms (SNPs) of IL10 gene could alter this cytokine
      production. The aim of this study was to investigate frequencies of IL10 alleles
      and genotypes in a group of individuals with RAS. Genomic DNA of 60 Iranian
      patients with RAS were typed for IL10 gene (C/A -1082, C/T -819, and C/A -592),
      using PCR-SSP method. Frequency of each allele and genotype was compared to
      control group. A significantly higher frequencies of the T allele at position 
      819 (p=0.006) and the A allele at position of -592 (p<0.001) were found in the
      patients with RAS group, when compared to the controls. IL10 GA genotype at
      position -1082 (p=0.007), CA genotype at position -592 (p=0.001), and CT genotype
      at position -819 (p=0.001) were significantly higher in the RAS patients. The
      results of this study suggest that certain SNPs of IL10 gene have association
      with predisposition of individuals to RAS. However, further multicenter studies
      should be conducted to confirm the results of this study.

PMID- 24564198
TI  - Delayed increases in microvascular pathology after experimental traumatic brain
      injury are associated with prolonged inflammation, blood-brain barrier
      disruption, and progressive white matter damage.
AB  - Traumatic brain injury (TBI) is a significant risk factor for chronic traumatic
      encephalopathy (CTE), Alzheimer's disease (AD), and Parkinson's disease (PD).
      Cerebral microbleeds, focal inflammation, and white matter damage are associated
      with many neurological and neurodegenerative disorders including CTE, AD, PD,
      vascular dementia, stroke, and TBI. This study evaluates microvascular
      abnormalities observed at acute and chronic stages following TBI in rats, and
      examines pathological processes associated with these abnormalities. TBI in adult
      rats was induced by controlled cortical impact (CCI) of two magnitudes. Brain
      pathology was assessed in white matter of the corpus callosum for 24 h to 3
      months following injury using immunohistochemistry (IHC). TBI resulted in focal
      microbleeds that were related to the magnitude of injury. At the lower magnitude
      of injury, microbleeds gradually increased over the 3 month duration of the
      study. IHC revealed TBI-induced focal abnormalities including blood-brain barrier
      (BBB) damage (IgG), endothelial damage (intercellular adhesion molecule 1 [ICAM
      1]), activation of reactive microglia (ionized calcium binding adaptor molecule 1
      [Iba1]), gliosis (glial fibrillary acidic protein [GFAP]) and macrophage-mediated
      inflammation (cluster of differentiation 68 [CD68]), all showing different
      temporal profiles. At chronic stages (up to 3 months), apparent myelin loss
      (Luxol fast blue) and scattered deposition of microbleeds were observed.
      Microbleeds were surrounded by glial scars and co-localized with CD68 and IgG
      puncta stainings, suggesting that localized BBB breakdown and inflammation were
      associated with vascular damage. Our results indicate that evolving white matter
      degeneration following experimental TBI is associated with significantly delayed
      microvascular damage and focal microbleeds that are temporally and regionally
      associated with development of punctate BBB breakdown and progressive
      inflammatory responses. Increased understanding of mechanisms underlying delayed
      microvascular damage following TBI could provide novel insights into chronic
      pathological responses to TBI and potential common mechanisms underlying TBI and
      neurodegenerative diseases.

PMID- 24564199
TI  - Guidelines for managing data and processes in bone and cartilage tissue
      engineering.
AB  - BACKGROUND: In the last decades, a wide number of researchers/clinicians involved
      in tissue engineering field published several works about the possibility to
      induce a tissue regeneration guided by the use of biomaterials. To this aim,
      different scaffolds have been proposed, and their effectiveness tested through in
      vitro and/or in vivo experiments. In this context, integration and meta-analysis
      approaches are gaining importance for analyses and reuse of data as, for example,
      those concerning the bone and cartilage biomarkers, the biomolecular factors
      intervening in cell differentiation and growth, the morphology and the
      biomechanical performance of a neo-formed tissue, and, in general, the scaffolds'
      ability to promote tissue regeneration. Therefore standards and ontologies are
      becoming crucial, to provide a unifying knowledge framework for annotating data
      and supporting the semantic integration and the unambiguous interpretation of
      novel experimental results. RESULTS: In this paper a conceptual framework has
      been designed for bone/cartilage tissue engineering domain, by now completely
      lacking standardized methods. A set of guidelines has been provided, defining the
      minimum information set necessary for describing an experimental study involved
      in bone and cartilage regenerative medicine field. In addition, a Bone/Cartilage
      Tissue Engineering Ontology (BCTEO) has been developed to provide a
      representation of the domain's concepts, specifically oriented to cells, and
      chemical composition, morphology, physical characterization of biomaterials
      involved in bone/cartilage tissue engineering research. CONCLUSIONS: Considering
      that tissue engineering is a discipline that traverses different semantic fields
      and employs many data types, the proposed instruments represent a first attempt
      to standardize the domain knowledge and can provide a suitable means to integrate
      data across the field.

PMID- 24564200
TI  - Fast discovery and visualization of conserved regions in DNA sequences using
      quasi-alignment.
AB  - BACKGROUND: Next Generation Sequencing techniques are producing enormous amounts
      of biological sequence data and analysis becomes a major computational problem.
      Currently, most analysis, especially the identification of conserved regions,
      relies heavily on Multiple Sequence Alignment and its various heuristics such as
      progressive alignment, whose run time grows with the square of the number and the
      length of the aligned sequences and requires significant computational resources.
      In this work, we present a method to efficiently discover regions of high
      similarity across multiple sequences without performing expensive sequence
      alignment. The method is based on approximating edit distance between segments of
      sequences using p-mer frequency counts. Then, efficient high-throughput data
      stream clustering is used to group highly similar segments into so called quasi
      alignments. Quasi-alignments have numerous applications such as identifying
      species and their taxonomic class from sequences, comparing sequences for
      similarities, and, as in this paper, discovering conserved regions across related
      sequences. RESULTS: In this paper, we show that quasi-alignments can be used to
      discover highly similar segments across multiple sequences from related or
      different genomes efficiently and accurately. Experiments on a large number of
      unaligned 16S rRNA sequences obtained from the Greengenes database show that the
      method is able to identify conserved regions which agree with known hypervariable
      regions in 16S rRNA. Furthermore, the experiments show that the proposed method
      scales well for large data sets with a run time that grows only linearly with the
      number and length of sequences, whereas for existing multiple sequence alignment
      heuristics the run time grows super-linearly. CONCLUSION: Quasi-alignment-based
      algorithms can detect highly similar regions and conserved areas across multiple
      sequences. Since the run time is linear and the sequences are converted into a
      compact clustering model, we are able to identify conserved regions fast or even
      interactively using a standard PC. Our method has many potential applications
      such as finding characteristic signature sequences for families of organisms and
      studying conserved and variable regions in, for example, 16S rRNA.

PMID- 24564201
TI  - Rigidity analysis of protein biological assemblies and periodic crystal
      structures.
AB  - BACKGROUND: We initiate in silico rigidity-theoretical studies of biological
      assemblies and small crystals for protein structures. The goal is to determine
      if, and how, the interactions among neighboring cells and subchains affect the
      flexibility of a molecule in its crystallized state. We use experimental X-ray
      crystallography data from the Protein Data Bank (PDB). The analysis relies on an
      effcient graph-based algorithm. Computational experiments were performed using
      new protein rigidity analysis tools available in the new release of our KINARI
      Web server http://kinari.cs.umass.edu. RESULTS: We provide two types of results:
      on biological assemblies and on crystals. We found that when only isolated
      subchains are considered, structural and functional information may be missed.
      Indeed, the rigidity of biological assemblies is sometimes dependent on the count
      and placement of hydrogen bonds and other interactions among the individual
      subchains of the biological unit. Similarly, the rigidity of small crystals may
      be affected by the interactions between atoms belonging to different unit cells.
      CONCLUSION: The rigidity analysis of a single asymmetric unit may not accurately
      reflect the protein's behavior in the tightly packed crystal environment. Using
      our KINARI software, we demonstrated that additional functional and rigidity
      information can be gained by analyzing a protein's biological assembly and/or
      crystal structure. However, performing a larger scale study would be
      computationally expensive (due to the size of the molecules involved). Overcoming
      this limitation will require novel mathematical and computational extensions to
      our software.

PMID- 24564202
TI  - Changes in gut bacterial populations and their translocation into liver and
      ascites in alcoholic liver cirrhotics.
AB  - BACKGROUND: The liver is the first line of defence against continuously occurring
      influx of microbial-derived products and bacteria from the gut. Intestinal
      bacteria have been implicated in the pathogenesis of alcoholic liver cirrhosis.
      Escape of intestinal bacteria into the ascites is involved in the pathogenesis of
      spontaneous bacterial peritonitis, which is a common complication of liver
      cirrhosis. The association between faecal bacterial populations and alcoholic
      liver cirrhosis has not been resolved. METHODS: Relative ratios of major
      commensal bacterial communities (Bacteroides spp., Bifidobacterium spp.,
      Clostridium leptum group, Enterobactericaea and Lactobacillus spp.) were
      determined in faecal samples from post mortem examinations performed on 42 males,
      including cirrhotic alcoholics (n = 13), non-cirrhotic alcoholics (n = 15), non
      alcoholic controls (n = 14) and in 7 healthy male volunteers using real-time
      quantitative PCR (RT-qPCR). Translocation of bacteria into liver in the autopsy
      cases and into the ascites of 12 volunteers with liver cirrhosis was also studied
      with RT-qPCR. CD14 immunostaining was performed for the autopsy liver samples.
      RESULTS: Relative ratios of faecal bacteria in autopsy controls were comparable
      to those of healthy volunteers. Cirrhotics had in median 27 times more bacterial
      DNA of Enterobactericaea in faeces compared to the healthy volunteers (p =
      0.011). Enterobactericaea were also the most common bacteria translocated into
      cirrhotic liver, although there were no statistically significant differences
      between the study groups. Of the ascites samples from the volunteers with liver
      cirrhosis, 50% contained bacterial DNA from Enterobactericaea, Clostridium leptum
      group or Lactobacillus spp.. The total bacterial DNA in autopsy liver was
      associated with the percentage of CD14 expression (p = 0.045). CD14 expression
      percentage in cirrhotics was significantly higher than in the autopsy controls (p
      = 0.004). CONCLUSIONS: Our results suggest that translocation of intestinal
      bacteria into liver may be involved as a one factor in the pathogenesis of
      alcoholic liver cirrhosis.

PMID- 24564203
TI  - ITGA6 gene silencing by RNA interference modulates the expression of a large
      number of cell migration-related genes in human thymic epithelial cells.
AB  - BACKGROUND: The thymic epithelium is the major microenvironmental component of
      the thymus, the primary lymphoid organ responsible for the generation of T
      lymphocytes. Thymic epithelial cells (TEC) control intrathymic T cell
      differentiation by means of distinct types of interactions. TEC constitutively
      produce chemokines and extracellular matrix ligands (such as laminin and
      fibronectin) and express corresponding receptors, which allow thymocytes to
      migrate in a very ordered fashion. We previously showed that laminin mediates
      TEC/thymocyte interactions in both mice and humans. More recently, we used RNAi
      technology to knock-down the ITGA5 gene (which encodes CD49e, the integrin alpha
      chain subunit of the fibronectin receptor VLA-5) in cultured human TEC. Using a
      similar strategy, herein we knocked-down the ITGA6 gene, which encodes CD49f, the
      alpha-chain of two integrin-type laminin receptors, namely VLA-6 (alpha6beta1)
      and alpha6beta4. RESULTS: We first confirmed that RNAi-induced knock-down of the
      ITGA6 gene was successful, at both transcription and translational levels, with a
      significant decrease in the membrane expression of CD49f, apart from CD49b, CD49c
      and CD49d, ascertained by cytofluorometry on living TEC. We also demonstrated
      that such knock-down promotes a decrease in cell adhesion to laminin. Using
      quantitative PCR, we demonstrated that gene expression of other integrin alpha
      chains were concomitantly down-regulated, particularly those which form other
      laminin receptors, including ITGA1, ITGA2 and ITGA7. Interestingly enough, LAMA1
      gene expression (whose corresponding protein chain is part of laminin-111) was
      largely increased in ITGA6 knocked-down TEC cultures. Lastly, the network
      complexity of gene expression under ITGA6 influence is much broader, since we
      found that other cell migration-related genes, namely those coding for various
      chemokines, are also modulated when IGTA6 is knocked-down. CONCLUSION: The data
      presented herein clearly show that down regulation of ITGA6 gene in the human
      thymic epithelium triggers a complex cascade of effects upon the expression
      levels of several other cell migration-related genes, including extracellular
      matrix and chemokine ligands and receptors. Taken together, these data unravel
      the concept that the expression of genes involved in controlling of thymocyte
      migration by the thymic microenvironment should be regarded as complex networks,
      so that a defect in the expression of one single gene may reflect in an amplified
      cascade with functional consequences for TEC adhesion onto the natural ligand and
      potential consequences upon the normal patterns of TEC/thymocyte interactions.

PMID- 24564205
TI  - Lateral gene transfer, rearrangement, reconciliation.
AB  - BACKGROUND: Models of ancestral gene order reconstruction have progressively
      integrated different evolutionary patterns and processes such as unequal gene
      content, gene duplications, and implicitly sequence evolution via reconciled gene
      trees. These models have so far ignored lateral gene transfer, even though in
      unicellular organisms it can have an important confounding effect, and can be a
      rich source of information on the function of genes through the detection of
      transfers of clusters of genes. RESULT: We report an algorithm together with its
      implementation, DeCoLT, that reconstructs ancestral genome organization based on
      reconciled gene trees which summarize information on sequence evolution, gene
      origination, duplication, loss, and lateral transfer. DeCoLT optimizes in
      polynomial time on the number of rearrangements, computed as the number of gains
      and breakages of adjacencies between pairs of genes. We apply DeCoLT to 1099 gene
      families from 36 cyanobacteria genomes. CONCLUSION: DeCoLT is able to reconstruct
      adjacencies in 35 ancestral bacterial genomes with a thousand gene families in a
      few hours, and detects clusters of co-transferred genes. DeCoLT may also be used
      with any relationship between genes instead of adjacencies, to reconstruct
      ancestral interactions, functions or complexes. AVAILABILITY: http://pbil.univ
      lyon1.fr/software/DeCoLT/

PMID- 24564204
TI  - A pilot study of FDG PET/CT detects a link between brown adipose tissue and
      breast cancer.
AB  - BACKGROUND: Breast cancer is the second most lethal cancer in women.
      Understanding biological mechanisms that cause progression of this disease could
      yield new targets for prevention and treatment. Recent experimental studies
      suggest that brown adipose tissue (BAT) may play a key role in breast cancer
      progression. The primary objective for this pilot study was to determine if the
      prevalence of active BAT in patients with breast cancer is increased compared to
      cancer patients with other malignancies. METHODS: We retrospectively analyzed
      data from 96 breast cancer patients who had FDG PET/CT scan for routine staging
      at the University of Maryland and 96 age- and weight-matched control female
      patients with other malignancies (predominantly colon cancer) who had undergone
      FDG PET/CT imaging on the same day. Data on the distribution (bilateral upper
      neck, supraclavicular and paraspinal regions) and intensity (SUVmax) of active
      BAT were evaluated by 2 Nuclear Medicine physicians, blinded to the clinical
      history. RESULTS: We found sufficient evidence to conclude that based on our
      sample data the prevalence of active BAT in breast cancer patients' group is
      significantly different from that in the control group. The estimated frequency
      of BAT activity was 3 fold higher in breast cancer patients as compared to
      controls with other cancers, (16.7% vs. 5.2%, respectively, p = 0.019). When
      patients were stratified by age in order to determine the possible impact of age
      related hormonal changes on active BAT among the younger women (<= 55 years of
      age), 25.6% breast cancer patients exhibited BAT activity compared to only 2.8%
      in control women (p = 0.007). In contrast, among the older women (> 55 years of
      age), the prevalence of active BAT was similar among breast cancer and control
      women (10.7% vs 6.7%). CONCLUSIONS: In breast cancer patients prevalence of BAT
      activity on FDGPET/CT is 3-fold greater than in age- and body weight-matched
      patients with other solid tumor malignancies; this difference is particularly
      striking among younger women aged < =55. In summary, our retrospective clinical
      data provide support to pursue prospective clinical and translational studies to
      further define the role of BAT in breast cancer development and progression.

PMID- 24564206
TI  - Regular heartbeat rhythm at the heartbeat initiation stage is essential for
      normal cardiogenesis at low temperature.
AB  - BACKGROUND: The development of blood flow in the heart is crucial for heart
      function and embryonic survival. Recent studies have revealed the importance of
      the extracellular matrix and the mechanical stress applied to the valve cushion
      that controls blood flow to the formation of the cardiac valve during
      embryogenesis. However, the events that trigger such valve formation and
      mechanical stress, and their temperature dependence have not been explained
      completely. Medaka (Oryzias latipes) inhabits a wide range of East Asia and
      adapts to a wide range of climates. We used medaka embryos from different genomic
      backgrounds and analyzed heartbeat characteristics including back-and-forth blood
      flow and bradyarrhythmia in embryos incubated at low temperature. We also used
      high-speed imaging analysis to examine the heartbeat of these animals after
      transient exposure to low temperature. RESULTS: Embryos of the Hd-rR medaka
      strain exhibited back-and-forth blood flow in the heart (blood regurgitation)
      after incubation at 15  degrees C. This regurgitation was induced by exposure to
      low temperature around the heartbeat initiation period and was related to
      abnormalities in the maintenance or pattern of contraction of the atrium or the
      atrioventricular canal. The Odate strain from the northern Japanese group
      exhibited normal blood flow after incubation at 15  degrees C. High-speed time
      lapse analysis of the heartbeat revealed that bradyarrhythmia occurred only in Hd
      rR embryos incubated at 15  degrees C. The coefficient of contraction, defined as
      the quotient of the length of the atrium at systole divided by its length at
      diastole, was not affected in either strain. The average heart rate after
      removing the effect of arrhythmia did not differ significantly between the two
      strains, suggesting that the mechanical stress of individual myocardial
      contractions and the total mechanical stress could be equivalent, regardless of
      the presence of arrhythmia or the heart rate. Test-cross experiments suggested
      that this circulation phenotype was caused by a single major genomic locus.
      CONCLUSIONS: These results suggest that cardiogenesis at low temperature requires
      a constant heartbeat. Abnormal contraction rhythms at the stage of heartbeat
      initiation may cause regurgitation at later stages. From the evolutionary
      viewpoint, strains that exhibit normal cardiogenesis during development at low
      temperature inhabit northern environments.

PMID- 24564207
TI  - Effectiveness of Micronutrient Powders (MNP) in women and children.
AB  - INTRODUCTION: More than 3.5 million women and children under five die each year
      in poor countries due to underlying undernutrition. Many of these are associated
      with concomitant micronutrient deficiencies. In the last decade point of use or
      home fortification has emerged to tackle the widespread micronutrient
      deficiencies. We in this review have estimated the effect of Micronutrient
      Powders (MNPs) on the health outcomes of women and children. METHODS: We
      systematically reviewed literature published up to November 2012 to identify
      studies describing the effectiveness of MNPs. We used a standardized abstraction
      and grading format to estimate the effect of MNPs by applying the standard Child
      Health Epidemiology Reference Group (CHERG) rules. RESULTS: We included 17
      studies in this review. MNPs significantly reduced the prevalence of anemia by
      34% (RR: 0.66, 95% CI: 0.57-0.77), iron deficiency anemia by 57% (RR: 0.43, 95%
      CI: 0.35-0.52) and retinol deficiency by 21% (RR: 0.79, 95% CI: 0.64, 0.98). It
      also significantly improved the hemoglobin levels (SMD: 0.98, 95% CI: 0.55-1.40).
      While there were no statistically significant impacts observed for serum ferritin
      and zinc deficiency. Our analysis shows no impact of MNPs on various
      anthropometric outcomes including stunting (RR: 0.92, 95% CI: 0.81, 1.04),
      wasting (RR: 1.13, 95% CI: 0.91, 1.40), underweight (RR:0.96, 95% CI: 0.83,
      1.10), HAZ (SMD: 0.04, 95% CI: -0.13, 0.22), WAZ (SMD: 0.05, 95% CI: -0.12, 0.23)
      and WHZ (SMD: 0.04, 95% CI: -0.13, 0.21), although showing favorable trends. MNPs
      were found to be associated with significant increase in diarrhea (RR: 1.04, 95%
      CI: 1.01, 1.06) with non-significant impacts on fever and URI. CONCLUSION: Our
      analysis of the effect of MNPs in children suggests benefit in improving anemia
      and hemoglobin however the lack of impact on growth and evidence of increased
      diarrhea requires careful consideration before recommending the intervention for
      implementing at scale.

PMID- 24564209
TI  - Towards accurate modeling of noncovalent interactions for protein rigidity
      analysis.
AB  - BACKGROUND: Protein rigidity analysis is an efficient computational method for
      extracting flexibility information from static, X-ray crystallography protein
      data. Atoms and bonds are modeled as a mechanical structure and analyzed with a
      fast graph-based algorithm, producing a decomposition of the flexible molecule
      into interconnected rigid clusters. The result depends critically on noncovalent
      atomic interactions, primarily on how hydrogen bonds and hydrophobic interactions
      are computed and modeled. Ongoing research points to the stringent need for
      benchmarking rigidity analysis software systems, towards the goal of increasing
      their accuracy and validating their results, either against each other and
      against biologically relevant (functional) parameters. We propose two new methods
      for modeling hydrogen bonds and hydrophobic interactions that more accurately
      reflect a mechanical model, without being computationally more intensive. We
      evaluate them using a novel scoring method, based on the B-cubed score from the
      information retrieval literature, which measures how well two cluster
      decompositions match. RESULTS: To evaluate the modeling accuracy of KINARI, our
      pebble-game rigidity analysis system, we use a benchmark data set of 20 proteins,
      each with multiple distinct conformations deposited in the Protein Data Bank.
      Cluster decompositions for them were previously determined with the RigidFinder
      method from Gerstein's lab and validated against experimental data. When KINARI's
      default tuning parameters are used, an improvement of the B-cubed score over a
      crude baseline is observed in 30% of this data. With our new modeling options,
      improvements were observed in over 70% of the proteins in this data set. We
      investigate the sensitivity of the cluster decomposition score with case studies
      on pyruvate phosphate dikinase and calmodulin. CONCLUSION: To substantially
      improve the accuracy of protein rigidity analysis systems, thorough benchmarking
      must be performed on all current systems and future extensions. We have measured
      the gain in performance by comparing different modeling methods for noncovalent
      interactions. We showed that new criteria for modeling hydrogen bonds and
      hydrophobic interactions can significantly improve the results. The two new
      methods proposed here have been implemented and made publicly available in the
      current version of KINARI (v1.3), together with the benchmarking tools, which can
      be downloaded from our software's website, http://kinari.cs.umass.edu.

PMID- 24564210
TI  - New karyotypes of Atlantic tree rats, genus Phyllomys (Rodentia: Echimyidae).
AB  - Phyllomys (Echimyidae, Rodentia) is a genus of Neotropical rodents with available
      cytogenetic data restricted to six out of 13 species, mainly based on simple
      staining methods, without detailed analyses. In this work, we present new
      karyotypes for Phyllomys lamarum (diploid number 2n = 56, fundamental number or
      number of autosomal arms FN = 102) and Phyllomys sp. (2n = 74, FN = 140) from the
      state of Minas Gerais, southeastern Brazil. We provide the first GTG- and CBG
      banding patterns, silver-staining of the nucleolar organizer regions (Ag-NORs),
      and fluorescence in situ hybridization (FISH) with telomeric and 45S rDNA probes
      of Phyllomys. In addition to examining their chromosomes and phenotypic
      characters, we sequenced mitochondrial DNA from the specimens analyzed to confirm
      their taxonomic identification. The comparison of the distinctive chromosome
      complements of our specimens with those of other species of Phyllomys already
      published allowed us to conclude that chromosome data may be very useful for the
      taxonomy of the genus, as no two species analyzed presented the same diploid and
      fundamental numbers (2n and FN). 

PMID- 24564208
TI  - Dynamic reorganization of the AC16 cardiomyocyte transcriptome in response to
      TNFalpha signaling revealed by integrated genomic analyses.
AB  - BACKGROUND: Defining cell type-specific transcriptomes in mammals can be
      challenging, especially for unannotated regions of the genome. We have developed
      an analytical pipeline called groHMM for annotating primary transcripts using
      global nuclear run-on sequencing (GRO-seq) data. Herein, we use this pipeline to
      characterize the transcriptome of an immortalized adult human ventricular
      cardiomyocyte cell line (AC16) in response to signaling by tumor necrosis factor
      alpha (TNFalpha), which is controlled in part by NF-kappaB, a key transcriptional
      regulator of inflammation. A unique aspect of this work is the use of the RNA
      polymerase II (Pol II) inhibitor alpha-amanitin, which we used to define a set of
      RNA polymerase I and III (Pol I and Pol III) transcripts. RESULTS: Using groHMM,
      we identified ~30,000 coding and non-coding transcribed regions in AC16 cells,
      which includes a set of unique Pol I and Pol III primary transcripts. Many of
      these transcripts have not been annotated previously, including enhancer RNAs
      originating from NF-kappaB binding sites. In addition, we observed that AC16
      cells rapidly and dynamically reorganize their transcriptomes in response to
      TNFalpha stimulation in an NF-kappaB-dependent manner, switching from a basal
      state to a proinflammatory state affecting a spectrum of cardiac-associated
      protein-coding and non-coding genes. Moreover, we observed distinct Pol II
      dynamics for up- and downregulated genes, with a rapid release of Pol II into
      productive elongation for TNFalpha-stimulated genes. As expected, the TNFalpha
      induced changes in the AC16 transcriptome resulted in corresponding changes in
      cognate mRNA and protein levels in a similar manner, but with delayed kinetics.
      CONCLUSIONS: Our studies illustrate how computational genomics can be used to
      characterize the signal-regulated transcriptome in biologically relevant cell
      types, providing new information about how the human genome is organized,
      transcribed and regulated. In addition, they show how alpha-amanitin can be used
      to reveal the Pol I and Pol III transcriptome. Furthermore, they shed new light
      on the regulation of the cardiomyocyte transcriptome in response to a
      proinflammatory signal and help to clarify the link between inflammation and
      cardiomyocyte function at the transcriptional level.

PMID- 24564211
TI  - DNA is structured as a linear "jigsaw puzzle" in the genomes of Arabidopsis,
      rice, and budding yeast.
AB  - Knowledge of how a genome is structured and organized from its constituent
      elements is crucial to understanding its biology and evolution. Here, we report
      the genome structuring and organization pattern as revealed by systems analysis
      of the sequences of three model species, Arabidopsis, rice and yeast, at the
      whole-genome and chromosome levels. We found that all fundamental function
      elements (FFE) constituting the genomes, including genes (GEN), DNA transposable
      elements (DTE), retrotransposable elements (RTE), simple sequence repeats (SSR),
      and (or) low complexity repeats (LCR), are structured in a nonrandom and
      correlative manner, thus leading to a hypothesis that the DNA of the species is
      structured as a linear "jigsaw puzzle". Furthermore, we showed that different FFE
      differ in their importance in the formation and evolution of the DNA jigsaw
      puzzle structure between species. DTE and RTE play more important roles than GEN,
      LCR, and SSR in Arabidopsis, whereas GEN and RTE play more important roles than
      LCR, SSR, and DTE in rice. The genes having multiple recognized functions play
      more important roles than those having single functions. These results provide
      useful knowledge necessary for better understanding genome biology and evolution
      of the species and for effective molecular breeding of rice. 

PMID- 24564212
TI  - Abnormal mitosis induced by wheat-rye 1R monosomic addition lines.
AB  - Octoploid triticale were derived from common wheat (Triticum aestivum L.
      'Mianyang11') * rye (Secale cereale L. 'Kustro'), and some progeny were obtained
      by the backcrossing of triticale with 'Mianyang11' followed by self
      fertilization. In situ hybridization using rye genomic DNA and repetitive
      sequences pAs1 and pSc119.2 as probes was used to analyze the mitotic chromosomes
      of these progeny. Three wheat-rye 1R monosomic addition lines and a wheat line
      (12FT-1685) containing a 1R and a 1BL.1RS translocation chromosome were
      identified. Abnormal mitosis was observed in the two lines. During mitosis of a
      1R monosomic addition line (3-8-20-1R-2), lagging chromosomes, micronuclei,
      chromosomal bridges, and the one pole segregation of 1R chromosome were observed.
      Abnormal mitotic behaviour of chromosomes was also observed in some of the self
      progeny plants of lines 12FT-1685 and 3-8-20-1R-2. These progeny contained 1R
      chromosome or 1R chromosome arm. In addition, 4B chromosomes were absent from one
      of the progeny of 3-8-20-1R-2. This abnormal mitotic behaviour of chromosomes was
      not observed in two other 1R monosomic addition lines. These results indicate
      that a single 1R chromosome added to wheat might cause abnormal mitotic behaviour
      of both wheat and rye chromosomes and different genetic variations might occurr
      among the sibling 1R monosomic addition lines. 

PMID- 24564213
TI  - Analysis of plastome and chondriome genome types in potato somatic hybrids from
      Solanum tuberosum * Solanum etuberosum.
AB  - Cytoplasm types of the potato somatic hybrids from Solanum tuberosum * Solanum
      etuberosum were analysed using chloroplast (cp) and mitochondrial (mt) organelle
      genomes-specific markers. Of the 29 markers (15 cpDNA and 14 mtDNA) amplified in
      the 26 genotypes, 5 cpDNA (H3, NTCP4, NTCP8, NTCP9, and ALC1/ALC3) and 13 mtDNA
      markers showed polymorphism. The cluster analysis based on the mtDNA markers
      detected higher diversity compared with the cpDNA markers. Presence of new mtDNA
      fragments of the markers, namely, T11-2, Nsm1, pumD, Nsm3, and Nsm4, were
      observed, while monomorphic loci revealed highly conserved genomic regions in the
      somatic hybrids. The study revealed that the somatic hybrids had diverse
      cytoplasm types consisting predominantly of T-, W-, and C-, with a few A- and S
      type cp genomes; and alpha-, beta-, and gamma-type mt genomes. Somatic
      hybridization has unique potential to widen the cytoplasm types of the cultivated
      gene pools from wild species through introgression by breeding methods. 

PMID- 24564214
TI  - Isolation and characterization of a wheat--Psathyrostachys huashanica 'Keng' 3Ns
      disomic addition line with resistance to stripe rust.
AB  - We isolated a wheat germplasm line, 22-2, which was derived from common wheat
      (Triticum aestivum '7182') and Psathyrostachys huashanica 'Keng' (2n = 2x = 14,
      NsNs). Genomic composition and homoeologous relationships of 22-2 was analyzed
      using cytology, genomic in situ hybridization (GISH), EST-SSR, and EST-STS to
      characterize the alien chromatin in the transfer line. The cytological
      investigations showed that the chromosome number and configuration were 2n = 44 =
      22 II. Mitotic and meiotic GISH using P. huashanica genomic DNA as the probe
      indicated that 22-2 contained a pair of P. huashanica chromosomes. The genomic
      affinities of the introduced P. huashanica chromosomes were determined by EST-SSR
      and EST-STS using multiple-loci markers from seven wheat homoeologous groups
      between the parents and addition line. One EST-SSR and 17 EST-STS markers, which
      were located on the homoeologous group 3 chromosomes of wheat, amplified
      polymorphic bands in 22-2 that were unique to P. huashanica. Thus, these markers
      suggested that the introduced Ns chromosome pair belonged to homoeologous group
      3, so we designated 22-2 as a 3Ns disomic addition line. Based on disease
      reaction to mixed races (CYR31, CYR32, and Shuiyuan14) of stripe rust in the
      adult stages, 22-2 was found to have high resistance to stripe rust, which was
      possibly derived from its P. huashanica parent. Consequently, the new disomic
      addition line 22-2 could be a valuable donor source for wheat improvement
      depending on the excellent agronomic traits, especially, the introduction of
      novel disease resistance genes into wheat during breeding programs. 

PMID- 24564215
TI  - Molecular phylogeny of black flies in the Simulium tuberosum (Diptera:
      Simuliidae) species group in Thailand.
AB  - Black flies are medically and ecologically significant insects. They are also
      interesting from an evolutionary standpoint regarding the role of chromosomal
      change and ecological adaptation. In this study, molecular genetic markers based
      on multiple gene sequences were used to assess genetic diversity and to infer
      phylogenetic relationships for a group of cytologically highly diverse black
      flies of the Simulium tuberosum species group in Thailand. Ecological affinities
      of the species were also investigated. High levels of genetic diversity were
      found in cytological species complexes, S. tani and S. doipuiense, and also in S.
      rufibasis, which was cytologically nearly monomorphic. The results highlight the
      necessity of integrating multilevel markers for fully understanding black fly
      biodiversity. Phylogenetic relationships based on multiple gene sequences were
      consistent with an existing dendrogram inferred from cytological and
      morphological data. Simulium tani is the most distinctive taxa among the members
      of the S. tubersosum species group in Thailand based on its divergent
      morphological characters. Molecular data supported the monophyletic status of S.
      tani, S. weji, and S. yuphae, but S. doipuiense and S. rufibasis were
      polyphyletic, most likely due to incomplete lineage sorting and inadequate
      phylogenetic signals. Ecological analyses revealed that members of the S.
      tuberosum species group have clearly different ecological niches. The results
      thus supported previous views of the importance of ecology in black fly
      evolution. 

PMID- 24564216
TI  - New highly polymorphic microsatellite markers for the aquatic angiosperm Ruppia
      cirrhosa reveal population diversity and differentiation.
AB  - Ruppia cirrhosa is a clonal monoecious plant phylogenetically associated to
      seagrass families such as Posidoniaceae and Cymodoceaceae. It inhabits shallow
      waters that are important for productivity and as a biodiversity reservoir. In
      this study, we developed 10 polymorphic microsatellite loci for R. cirrhosa.
      Additionally, we obtained cross-amplification for two microsatellites previously
      described for Ruppia maritima. These 12 markers were tested in four R. cirrhosa
      populations from the southwest of Europe. The number of alleles per locus was
      high for most of the markers, ranging from 4 to 13. Two populations (Sicily and
      Cadiz) showed heterozygote deficit (p < 0.001). The four populations (Sicily,
      Murcia, Cadiz, and Tavira) were significantly differentiated (F(ST) ? 0; p <
      0.001), corroborating the usefulness of these microsatellites on R. cirrhosa
      population genetics.

PMID- 24564218
TI  - Interfacial behavior and activity of laccase and bilirubin oxidase on bare gold
      surfaces.
AB  - Two blue multicopper oxidases (MCOs) (viz. Trametes hirsuta laccase (ThLc) and
      Myrothecium verrucaria bilirubin oxidase (MvBOx)) were immobilized on bare
      polycrystalline gold (Au) surfaces by direct adsorption from both dilute and
      concentrated enzyme solutions. The adsorption was studied in situ by means of
      null ellipsometry. Moreover, both enzyme-modified and bare Au electrodes were
      investigated in detail by atomic force microscopy (AFM) as well as
      electrochemically. When adsorbed from dilute solutions (0.125 and 0.25 mg mL-1 in
      the cases of ThLc and MvBOx, respectively), the amounts of enzyme per unit area
      were determined to be ca. 1.7 and 4.8 pmol cm-2, whereas the protein film
      thicknesses were determined to be 29 and 30 A for ThLc and MvBOx, respectively. A
      well-pronounced bioelectrocatalytic reduction of molecular oxygen (O2) was
      observed on MvBOx/Au biocathodes, whereas this was not the case for ThLc-modified
      Au electrodes (i.e., adsorbed ThLc was catalytically inactive). The initially
      observed apparent k(cat)(app) values for adsorbed MvBOx and the enzyme in
      solution were found to be very close to each other (viz. 54 and 58 s-1,
      respectively (pH 7.4, 25  degrees C)). However, after 3 h of operation of
      MvBOx/Au biocathodes, kcatapp dropped to 23 s-1. On the basis of the experimental
      results, conformational changes of the enzymes (in all likelihood, their
      flattening on the Au surface) were suggested to explain the deactivation of MCOs
      on the bare Au electrodes.

PMID- 24564219
TI  - Successful emotion regulation skills application predicts subsequent reduction of
      symptom severity during treatment of major depressive disorder.
AB  - OBJECTIVE: Deficits in emotion regulation (ER) skills are considered a putative
      maintaining factor for major depressive disorder (MDD) and hence a promising
      target in the treatment of MDD. However, to date, the association between the
      successful application of arguably adaptive ER skills and changes in depressive
      symptom severity (DSS) has yet to be investigated over the course of treatment.
      Thus, the primary aim of this study was to clarify reciprocal prospective
      associations between successful ER skills application and DSS over the course of
      inpatient cognitive behavioral therapy for MDD. Additionally, we explored whether
      such associations would differ across specific ER skills. METHOD: We assessed
      successful ER skills application and DSS 4 times during the first 3 weeks of
      treatment in 152 inpatients (62.5% women, average age 45.6 years) meeting
      criteria for MDD. We first tested whether successful skills application and
      depression were cross-sectionally associated by computing Pearson's correlations.
      Then, we utilized latent curve modeling to test whether changes in successful
      skills application were negatively associated with changes in DSS during
      treatment. Finally, we used latent change score models to clarify whether
      successful skills application would predict subsequent reduction of DSS. RESULTS:
      Cross-sectionally, successful ER skills application was associated with lower
      levels of DSS at all assessment times, and an increase of successful skills
      application during treatment was associated with a decrease of DSS. Moreover,
      successful overall ER skills application predicted subsequent changes in DSS (but
      not vice versa). Finally, strength of associations between successful application
      and DSS differed across specific ER skills. Among a broad range of potentially
      adaptive skills, only the abilities to tolerate negative emotions and to actively
      modify undesired emotions were significantly associated with subsequent
      improvement in DSS. CONCLUSIONS: Systematically enhancing health-relevant ER
      skills with specific interventions may help reduce DSS in patients suffering from
      MDD.

PMID- 24564220
TI  - Development and tuning of an original search engine for patent libraries in
      medicinal chemistry.
AB  - BACKGROUND: The large increase in the size of patent collections has led to the
      need of efficient search strategies. But the development of advanced text-mining
      applications dedicated to patents of the biomedical field remains rare, in
      particular to address the needs of the pharmaceutical & biotech industry, which
      intensively uses patent libraries for competitive intelligence and drug
      development. METHODS: We describe here the development of an advanced retrieval
      engine to search information in patent collections in the field of medicinal
      chemistry. We investigate and combine different strategies and evaluate their
      respective impact on the performance of the search engine applied to various
      search tasks, which covers the putatively most frequent search behaviours of
      intellectual property officers in medical chemistry: 1) a prior art search task;
      2) a technical survey task; and 3) a variant of the technical survey task,
      sometimes called known-item search task, where a single patent is targeted.
      RESULTS: The optimal tuning of our engine resulted in a top-precision of 6.76%
      for the prior art search task, 23.28% for the technical survey task and 46.02%
      for the variant of the technical survey task. We observed that co-citation
      boosting was an appropriate strategy to improve prior art search tasks, while IPC
      classification of queries was improving retrieval effectiveness for technical
      survey tasks. Surprisingly, the use of the full body of the patent was always
      detrimental for search effectiveness. It was also observed that normalizing
      biomedical entities using curated dictionaries had simply no impact on the search
      tasks we evaluate. The search engine was finally implemented as a web-application
      within Novartis Pharma. The application is briefly described in the report.
      CONCLUSIONS: We have presented the development of a search engine dedicated to
      patent search, based on state of the art methods applied to patent corpora. We
      have shown that a proper tuning of the system to adapt to the various search
      tasks clearly increases the effectiveness of the system. We conclude that
      different search tasks demand different information retrieval engines' settings
      in order to yield optimal end-user retrieval.

PMID- 24564221
TI  - Admission glucose and coagulopathy occurrence in patients with traumatic brain
      injury.
AB  - INTRODUCTION: Coagulopathy after traumatic brain injury (TBI) is a frequent event
      and is associated with patients' prognosis. TBI is also associated with a stress
      response that includes hyperglycemia. This study investigated if coagulopathy
      occurrence is associated with admission blood glucose levels in patients with
      TBI. METHODS: This study retrospectively evaluated patients with TBI who were
      admitted to a neurosurgical department over a 4-year period. Coagulopathy was
      defined as an aPTT >40 seconds and/or INR >1.2 and/or a platelet count <120*10(9)
      per litre. RESULTS: One-hundred and forty-nine patients were included in the
      study. Thirty-four patients developed coagulopathy. Patients with coagulopathy
      had significantly lower haemoglobin levels, increased INR and increased aPTT.
      Patients with severe TBI had more frequent coagulopathy. Patients with severe TBI
      had significant higher serum glucose levels compared to patients with mild TBI.
      Using ROC curves it was found that a serum glucose of 151 mg dl(-1) was the
      threshold for the discrimination of patients that developed coagulopathy.
      Logistic regression analysis revealed that serum glucose greater than 151 mg dl(
      1) and haemoglobin levels lower than 12.4 mg dL(-1) were significantly associated
      with coagulopathy occurrence. CONCLUSION: Coagulopathy frequently occur after
      TBI. Patients with lower GCS score and lower haemoglobin levels and increased
      blood glucose levels at admission are at greater risk.

PMID- 24564222
TI  - Parental perspectives on the communication abilities of their daughters with Rett
      syndrome.
AB  - OBJECTIVE: This study describes, from the perspective of parents, how females
      with Rett syndrome communicate in everyday life and the barriers and facilitators
      to successful communication. METHODS: Sixteen interviews were conducted with
      parents with a daughter with Rett syndrome with a pathogenic mutation in the
      methyl-CpG-binding protein 2 gene. Interviews were recorded and transcribed
      verbatim. Transcripts were analysed using directed content analysis. RESULTS: All
      parents reported their daughters were able to express discomfort and pleasure,
      and make requests and choices using a variety of modalities including
      vocalisations, body movements and eye gaze. Parents also reported their daughters
      understood most of what they said and that the level of functional abilities,
      such as mobility, and environmental factors, such as characteristics of the
      communication partner, influenced successful communication. CONCLUSIONS: The
      perspectives of parents are integral to the assessment of communication abilities
      and have the potential to inform communication interventions for girls and women
      with Rett syndrome.

PMID- 24564224
TI  - The interface of psychiatry and oncology.

PMID- 24564223
TI  - Mature Epitope Density--a strategy for target selection based on
      immunoinformatics and exported prokaryotic proteins.
AB  - BACKGROUND: Current immunological bioinformatic approaches focus on the
      prediction of allele-specific epitopes capable of triggering immunogenic
      activity. The prediction of major histocompatibility complex (MHC) class I
      epitopes is well studied, and various software solutions exist for this purpose.
      However, currently available tools do not account for the concentration of
      epitope products in the mature protein product and its relation to the
      reliability of target selection. RESULTS: We developed a computational strategy
      based on measuring the epitope's concentration in the mature protein, called
      Mature Epitope Density (MED). Our method, though simple, is capable of
      identifying promising vaccine targets. Our online software implementation
      provides a computationally light and reliable analysis of bacterial exoproteins
      and their potential for vaccines or diagnosis projects against pathogenic
      organisms. We evaluated our computational approach by using the Mycobacterium
      tuberculosis (Mtb) H37Rv exoproteome as a gold standard model. A literature
      search was carried out on 60 out of 553 Mtb's predicted exoproteins, looking for
      previous experimental evidence concerning their possible antigenicity. Half of
      the 60 proteins were classified as highest scored by the MED statistic, while the
      other half were classified as lowest scored. Among the lowest scored proteins,
      ~13% were confirmed as not related to antigenicity or not contributing to the
      bacterial pathogenicity, and 70% of the highest scored proteins were confirmed as
      related. There was no experimental evidence of antigenic or pathogenic
      contributions for three of the highest MED-scored Mtb proteins. Hence, these
      three proteins could represent novel putative vaccine and drug targets for Mtb. A
      web version of MED is publicly available online at http://med.mmci.uni
      saarland.de/. CONCLUSIONS: The software presented here offers a practical and
      accurate method to identify potential vaccine and diagnosis candidates against
      pathogenic bacteria by "reading" results from well-established reverse
      vaccinology software in a novel way, considering the epitope's concentration in
      the mature portion of the protein.

PMID- 24564225
TI  - An evolutionary ratchet leading to loss of elongation factors in eukaryotes.
AB  - BACKGROUND: The GTPase eEF1A is the eukaryotic factor responsible for the
      essential, universal function of aminoacyl-tRNA delivery to the ribosome.
      Surprisingly, eEF1A is not universally present in eukaryotes, being replaced by
      the paralog EFL independently in multiple lineages. The driving force behind this
      unusually frequent replacement is poorly understood. RESULTS: Through sequence
      searching of genomic and EST databases, we find a striking association of eEF1A
      replacement by EFL and loss of eEF1A's guanine exchange factor, eEF1Balpha,
      suggesting that EFL is able to spontaneously recharge with GTP. Sequence
      conservation and homology modeling analyses indicate several sequence regions
      that may be responsible for EFL's lack of requirement for eEF1Balpha.
      CONCLUSIONS: We propose that the unusual pattern of eEF1A, eEF1Balpha and EFL
      presence and absence can be explained by a ratchet-like process: if either eEF1A
      or eEF1Balpha diverges beyond functionality in the presence of EFL, the system is
      unable to return to the ancestral, eEF1A:eEFBalpha-driven state.

PMID- 24564226
TI  - Effectiveness of tigecycline-based versus colistin- based therapy for treatment
      of pneumonia caused by multidrug-resistant Acinetobacter baumannii in a critical
      setting: a matched cohort analysis.
AB  - BACKGROUND: Colistin and tigecycline have both been shown good in vitro activity
      among multi-drug resistant Acinetobacter baumannii (MDRAB). A comparative study
      of colistin versus tigecycline for MDRAB pneumonia is lacking. METHODS: The study
      enrolled adults with MDRAB pneumonia admitted to intensive care units at a
      referral medical center during 2009-2010. Since there were no standardized
      minimum inhibitory concentration (MIC) interpretation criteria of tigecycline
      against A. baumannii, MIC of tigecycline was not routinely tested at our
      hospital. During the study periods, MIC of colistin was not routinely tested
      also. We consider both colistin and tigecycline as definite treatments of MDRAB
      pneumonia. Patients who received tigecycline were selected as potential controls
      for those who had received colistin. We performed a propensity score analysis, by
      considering the criteria of age, gender, underlying diseases, and disease
      severity, in order to match and equalize potential prognostic factors and
      severity in the two groups. RESULTS: A total of 294 adults with MDRAB pneumonia
      were enrolled, including 119 who received colistin and 175 who received
      tigecycline. We matched 84 adults who received colistin with an equal number of
      controls who received tigecycline. The two well matched cohorts share similar
      characteristics: the propensity scores are colistin: 0.37 vs. tigecycline: 0.37,
      (P = .97); baseline creatinine (1.70 vs. 1.81, P = .50), and the APACHE II score
      (21.6 vs. 22.0, P = .99). The tigecycline group has an excess mortality of 16.7%
      (60.7% vs. 44%, 95% confidence interval 0.9% - 32.4%, P = .04). The excess
      mortality of tigecycline is significant only among those with MIC >2 MUg/mL
      (10/12 vs. 37/84, P = .01), but not for those with MIC ? 2 MUg/mL (4/10 vs.
      37/84, P = .81). CONCLUSIONS: Our data disfavors the use of tigecycline-based
      treatment in treating MDRAB pneumonia when tigecycline and colistin
      susceptibilities are unknown, since choosing tigecycline-based treatment might
      result in higher mortality. The excess mortality of tigecycline-based group may
      be related to higher MIC of tigecycline (> 2 MUg/mL). Choosing tigecycline
      empirically for treating MDRAB pneumonia in the critical setting should be
      cautious.

PMID- 24564227
TI  - Gene tree correction guided by orthology.
AB  - BACKGROUND: Reconciled gene trees yield orthology and paralogy relationships
      between genes. This information may however contradict other information on
      orthology and paralogy provided by other footprints of evolution, such as
      conserved synteny. RESULTS: We explore a way to include external information on
      orthology in the process of gene tree construction. Given an initial gene tree
      and a set of orthology constraints on pairs of genes or on clades, we give
      polynomial-time algorithms for producing a modified gene tree satisfying the set
      of constraints, that is as close as possible to the original one according to the
      Robinson-Foulds distance. We assess the validity of the modifications we propose
      by computing the likelihood ratio between initial and modified trees according to
      sequence alignments on Ensembl trees, showing that often the two trees are
      statistically equivalent. AVAILABILITY: Software and data available upon request
      to the corresponding author.

PMID- 24564229
TI  - Folate-vinca alkaloid conjugates for cancer therapy: a structure-activity
      relationship.
AB  - Vintafolide is a potent folate-targeted vinca alkaloid small molecule drug
      conjugate (SMDC) that has shown promising results in multiple clinical oncology
      studies. Structurally, vintafolide consists of 4 essential modules: (1) folic
      acid, (2) a hydrophilic peptide spacer, (3) a disulfide-containing, self
      immolative linker, and (4) the cytotoxic drug, desacetylvinblastine hydrazide
      (DAVLBH). Here, we report a structure-activity study evaluating the biological
      impact of (i) substituting DAVLBH within the vintafolide molecule with other
      vinca alkaloid analogues such as vincristine, vindesine, vinflunine, or
      vinorelbine; (ii) substituting the naturally (S)-configured Asp-Arg-Asp-Asp-Cys
      peptide with alternative hydrophilic spacers of varied composition; and (iii)
      varying the composition of the linker module. A series of vinca alkaloid
      containing SMDCs were synthesized and purified by HPLC and LCMS. The SMDCs were
      screened in vitro against folate receptor (FR)-positive cells, and anti-tumor
      activity was tested against well-established subcutaneous FR-positive tumor
      xenografts. The cytotoxic and anti-tumor activity was directly compared to that
      produced by vintafolide. Among all the folate vinca alkaloid SMDCs tested, DAVLBH
      containing SMDCs were active, while those constructed with vincristine,
      vindesine, or vinorelbine analogues failed to produce meaningful biological
      activity. Within the DAVLBH series, having a bioreleasable, self-immolative
      linker system was found to be critical for activity since multiple analogues
      constructed with thioether-based linkers all failed to produce meaningful
      activity both in vitro and in vivo. Substitutions of some or all of the natural
      amino acids within vintafolide's hydrophilic spacer module did not significantly
      change the in vitro or in vivo potency of the SMDCs. Vintafolide remains one of
      the most potent folate-vinca alkaloid SMDCs produced to date, and continued
      clinical development is warranted. 

PMID- 24564228
TI  - ARID5B polymorphism confers an increased risk to acquire specific MLL
      rearrangements in early childhood leukemia.
AB  - BACKGROUND: Acute leukemia in early age (EAL) is characterized by acquired
      genetic alterations such as MLL rearrangements (MLL-r). The aim of this case
      controlled study was to investigate whether single nucleotide polymorphisms
      (SNPs) of IKZF1, ARID5B, and CEBPE could be related to the onset of EAL cases
      (<24 months-old at diagnosis). METHODS: The SNPs (IKZF1 rs11978267, ARID5B
      rs10821936 and rs10994982, CEBPE rs2239633) were genotyped in 265 cases [169
      acute lymphoblastic leukemia (ALL) and 96 acute myeloid leukaemia (AML)] and 505
      controls by Taqman allelic discrimination assay. Logistic regression was used to
      evaluate the association between SNPs of cases and controls, adjusted on skin
      color and/or age. The risk was determined by calculating odds ratios (ORs) with
      95% confidence interval (CI). RESULTS: Children with the IKZF1 SNP had an
      increased risk of developing MLL-germline ALL in white children. The
      heterozygous/mutant genotype in ARID5B rs10994982 significantly increased the
      risk for MLL-germline leukemia in white and non-white children (OR 2.60, 95% CI:
      1.09-6.18 and OR 3.55, 95% CI: 1.57-8.68, respectively). The heterozygous
      genotype in ARID5B rs10821936 increased the risk for MLL-r leukemia in both white
      and non-white (OR 2.06, 95% CI: 1.12-3.79 and OR 2.36, 95% CI: 1.09-5.10,
      respectively). Furthermore, ARID5B rs10821936 conferred increased risk for MLL
      MLLT3 positive cases (OR 7.10, 95% CI:1.54-32.68). Our data do not show evidence
      that CEBPE rs2239633 confers increased genetic susceptibility to EAL.
      CONCLUSIONS: IKZF1 and CEBPE variants seem to play a minor role in genetic
      susceptibility to EAL, while ARID5B rs10821936 increased the risk of MLL-MLLT3.
      This result shows that genetic susceptibility could be associated with the
      differences regarding MLL breakpoints and partner genes.

PMID- 24564231
TI  - Efficient digest of high-throughput sequencing data in a reproducible report.
AB  - BACKGROUND: High-throughput sequencing (HTS) technologies are spearheading the
      accelerated development of biomedical research. Processing and summarizing the
      large amount of data generated by HTS presents a non-trivial challenge to
      bioinformatics. A commonly adopted standard is to store sequencing reads aligned
      to a reference genome in SAM (Sequence Alignment/Map) or BAM (Binary
      Alignment/Map) files. Quality control of SAM/BAM files is a critical checkpoint
      before downstream analysis. The goal of the current project is to facilitate and
      standardize this process. RESULTS: We developed bamchop, a robust program to
      efficiently summarize key statistical metrics of HTS data stored in BAM files,
      and to visually present the results in a formatted report. The report documents
      information about various aspects of HTS data, such as sequencing quality,
      mapping to a reference genome, sequencing coverage, and base frequency. Bamchop
      uses the R language and Bioconductor packages to calculate statistical matrices
      and the Sweave utility and associated LaTeX markup for documentation. Bamchop's
      efficiency and robustness were tested on BAM files generated by local sequencing
      facilities and the 1000 Genomes Project. Source code, instruction and example
      reports of bamchop are freely available from https://github.com/CBMi-BiG/bamchop.
      CONCLUSIONS: Bamchop enables biomedical researchers to quickly and rigorously
      evaluate HTS data by providing a convenient synopsis and user-friendly reports.

PMID- 24564230
TI  - Endometrial gene expression profiling in pregnant Meishan and Yorkshire pigs on
      day 12 of gestation.
AB  - BACKGROUND: Litter size in pigs is a major factor affecting the profitability in
      the pig industry. The peri-implantation window in pigs is characterized by the
      coordinated interactions between the maternal uterine endometrium and the rapidly
      elongating conceptuses and represents a period of time during which a large
      percentage of the developing conceptuses are lost. However, the gene expression
      and regulatory networks in the endometrium contributing to the establishment of
      the maternal: placental interface remain poorly understood. RESULTS: We
      characterized the endometrial gene expression profile during the peri
      implantation stage of development by comparing two breeds that demonstrate very
      different reproductive efficiencies. We employed the porcine Affymetrix
      GeneChip(r) to assay the transcriptomic profiles of genes expressed in the
      uterine endometrium obtained from Meishan and Yorkshire gilts (n = 4 for each
      breed) on day 12 of gestation (M12 and Y12, respectively). Total of 17,076
      probesets were identified as "present" in at least two arrays. A mixed model
      based statistical analysis predicted a total of 2,656 (q < 0.1) transcripts as
      differentially expressed between Meishan and Yorkshire pigs. Eighteen
      differentially expressed transcripts of interest were validated by quantitative
      real-time PCR. Gene ontology (GO) annotation revealed that the known functions of
      the differentially expressed genes were involved in a series of important
      biological processes relevant to early pregnancy establishment in the pig.
      CONCLUSIONS: The results identified endometrial gene expression profiles of two
      breeds differing in litter size and identified candidate genes that are related
      to known physiological pathways related to reproductive prolificacy. These
      findings provide a deeper understanding of molecular pathways differing between
      two breeds at the critical peri-implantation stage of pregnancy, which can be
      utilized to better understand the events contributing to pregnancy establishment
      in the pig.

PMID- 24564233
TI  - Crystal structure anisotropy explains anomalous elastic properties of nanorods.
AB  - It is demonstrated that the frequency of the extensional vibrational mode of a
      nanorod made of an elastically anisotropic crystalline material deviates widely
      from the predictions of the theories based on the analysis of the long-wavelength
      limit. The dispersion relation for the fundamental extensional mode of a gold rod
      grown in the [100] direction is calculated and found to be in excellent agreement
      with experimental data obtained from the transient optical absorption
      measurements on gold nanorods. This explains an anomaly in the elastic properties
      of nanorods which was previously attributed to a 26% decrease in Young's modulus
      for nanorods compared to its bulk value. The developed approach allows one to
      investigate the role of the crystal structure anisotropy for acoustic phonons in
      nanorods and nanowires made of any metal or semiconductor material having cubic
      crystal structure. 

PMID- 24564232
TI  - Assessment of depression in a rodent model of spinal cord injury.
AB  - Despite an increased incidence of depression in patients after spinal cord injury
      (SCI), there is no animal model of depression after SCI. To address this, we used
      a battery of established tests to assess depression after a rodent contusion
      injury. Subjects were acclimated to the tasks, and baseline scores were collected
      before SCI. Testing was conducted on days 9-10 (acute) and 19-20 (chronic)
      postinjury. To categorize depression, subjects' scores on each behavioral measure
      were averaged across the acute and chronic stages of injury and subjected to a
      principal component analysis. This analysis revealed a two-component structure,
      which explained 72.2% of between-subjects variance. The data were then analyzed
      with a hierarchical cluster analysis, identifying two clusters that differed
      significantly on the sucrose preference, open field, social exploration, and
      burrowing tasks. One cluster (9 of 26 subjects) displayed characteristics of
      depression. Using these data, a discriminant function analysis was conducted to
      derive an equation that could classify subjects as "depressed" on days 9-10. The
      discriminant function was used in a second experiment examining whether the
      depression-like symptoms could be reversed with the antidepressant, fluoxetine.
      Fluoxetine significantly decreased immobility in the forced swim test (FST) in
      depressed subjects identified with the equation. Subjects that were depressed and
      treated with saline displayed significantly increased immobility on the FST,
      relative to not depressed, saline-treated controls. These initial experiments
      validate our tests of depression, generating a powerful model system for further
      understanding the relationships between molecular changes induced by SCI and the
      development of depression.

PMID- 24564236
TI  - Design and fabrication of branched polyamine functionalized mesoporous silica: an
      efficient absorbent for water remediation.
AB  - A novel branched polyamine (polyethyleneimine, PEI) functionalized mesoporous
      silica (MS) adsorbent is developed via a facile "grafting-to" approach. X-ray
      photoelectron spectroscopy (XPS) and Fourier transform infrared (FT-IR)
      spectroscopy verified the effective surface functionalization of MS with
      monolayer and polymer. The transmission electron microscopy (TEM) was employed to
      reveal the morphology of the fabricated materials. The adsorption behavior of the
      polyamine functionalized mesoporous silica (MS-PEI) is assessed against anionic
      dyes. The adsorbent characteristics of MS-PEI are compared with a monolayer
      platform comprising of 3-aminopropyltriethoxy silane (APTES) functionalized
      mesoporous silica (MS-APTES). The adsorption behavior of the MS-PEI and MS-APTES
      toward anionic dyes is further evaluated by studying the effect of adsorbent
      dosage, pH, contact time, and temperature. Langmuir and Freundlich isotherm
      models are employed to understand the adsorption mechanism. The obtained kinetic
      data support a pseudo-second-order adsorption behavior for both monolayer and
      polymer functionalized MS. The associated thermodynamic parameters (DeltaG
      degrees , DeltaH degrees , and DeltaS degrees ) reveal that the process of
      adsorption with MS-PEI is more spontaneous and energetically favored as compared
      to the adsorption with MS-APTES. Taken together, the novel adsorbent system
      derived from a combination of MS and branched polymer (MS-PEI) shows the higher
      absorption efficiency and capacity toward the anionic dyes than the monolayer
      based adsorbent (MS-APTES). 

PMID- 24564237
TI  - Coarse-grain model for natural cellulose fibrils in explicit water.
AB  - Understanding biomass structure and dynamics on multiple time and length scales
      is important for the development of cellulosic biofuels. To this aim, we have
      developed a coarse-grain (CG) model for molecular dynamics (MD) simulations of
      cellulose fibrils in explicit water based on target observables from fully
      atomistic simulations. This model examines the significance of the presence of
      explicit solvent and compares results with the previous, implicit solvent CG
      cellulose models. The present, constraint-free CG model is used to generate a
      series of noncrystalline fibril structures using a coupling parameter, lambda,
      between fully crystalline and fully amorphous potentials. By exploring various
      structural parameters, including the root-mean-square deviation, root-mean-square
      fluctuations, radius of gyration, and persistence length, we find the crystalline
      to-amorphous state transition takes place at lambda ~ 0.386. The persistence
      length of cellulose fibril in the transition region corresponds to that of native
      cellulose fibrils. The transition between crystalline and amorphous fibrils
      occurs at larger values of lambda in explicit water than in the implicit case.
      Detailed analysis of individual energetic contribution to the transition reveals
      that the nonbonded interactions, in particular, that of cellulose-water
      interaction, plays a significant role in the observed crystalline to amorphous
      transition of cellulose fibril. The present study thus highlights the importance
      of solvent presence that cannot be adequately described with the previous
      implicit solvent model. The present method provides an accurate and constraint
      free approach for deriving a variety of structures of cellulose in water, with a
      wide range of crystallinity, suitable for incorporation into large-scale models
      of lignocellulosic biomass. 

PMID- 24564235
TI  - Treatment of severe and moderate acute malnutrition in low- and middle-income
      settings: a systematic review, meta-analysis and Delphi process.
AB  - BACKGROUND: Globally, moderate acute malnutrition (MAM) and severe acute
      malnutrition (SAM) affect approximately 52 million children under five. This
      systematic review evaluates the effectiveness of interventions for SAM including
      the World Health Organization (WHO) protocol for inpatient management and
      community-based management with ready-to-use-therapeutic food (RUTF), as well as
      interventions for MAM in children under five years in low- and middle-income
      countries. METHODS: We systematically searched the literature and included 14
      studies in the meta-analysis. Study quality was assessed using CHERG adaptation
      of GRADE criteria. A Delphi process was undertaken to complement the systematic
      review in estimating case fatality and recovery rates that were necessary for
      modelling in the Lives Saved Tool (LiST). RESULTS: Case fatality rates for
      inpatient treatment of SAM using the WHO protocol ranged from 3.4% to 35%. For
      community-based treatment of SAM, children given RUTF were 51% more likely to
      achieve nutritional recovery than the standard care group. For the treatment of
      MAM, children in the RUSF group were significantly more likely to recover and
      less likely to be non-responders than in the CSB group. In both meta-analyses,
      weight gain in the intervention group was higher, and although statistically
      significant, these differences were small. Overall limitations in our analysis
      include considerable heterogeneity in many outcomes and an inability to evaluate
      intervention effects separate from commodity effect. The Delphi process indicated
      that adherence to standardized protocols for the treatment of SAM and MAM should
      have a marked positive impact on mortality and recovery rates; yet, true
      consensus was not achieved. CONCLUSIONS: Gaps in our ability to estimate
      effectiveness of overall treatment approaches for SAM and MAM persist. In
      addition to further impact studies conducted in a wider range of settings, more
      high quality program evaluations need to be conducted and the results
      disseminated.

PMID- 24564239
TI  - Low toxicity beta-cyclodextrin-caged 4,4'-bipyridinium-bis(siloxane): synthesis
      and evaluation.
AB  - The toxicity of viologens can be significantly reduced by including them in tight
      [2]rotaxane structures alongside beta-cyclodextrin, thus turning them into
      candidates of pharmaceutical interest. Here, we report a synthesis pathway for a
      benign viologen, by capping a small beta-cyclodextrin-caged molecule, the 4,4'
      bipyridine, with minimal-length presynthesized axle-stopper segments of the
      propyl-3-pentamethyldisiloxane type. After 90 min from the oral administration to
      laboratory mice, the product concentration in the bloodstream reaches a value
      equivalent to 0.634% of the initial dose of 800 mg.kg(-1). As compared to the
      nude viologen having the same structure, which proved to be lethal in doses of 40
      mg.kg(-1), the product induces reversible morphological changes in the liver,
      kidney, lung, and cerebellum, up to a dose of 400 mg.kg(-1), with higher dosages
      giving rise to a chronic slow evolution.

PMID- 24564238
TI  - Signal extraction from movies of honeybee brain activity: the ImageBee plugin for
      KNIME.
AB  - BACKGROUND: In the antennal lobe, a dedicated olfactory center of the honeybee
      brain, odours are encoded as activity patterns of coding units, the so-called
      glomeruli. Optical imaging with calcium-sensitive dyes allows us to record these
      activity patterns and to gain insight into olfactory information processing in
      the brain. METHOD: We introduce ImageBee, a plugin for the data analysis platform
      KNIME. ImageBee provides a variety of tools for processing optical imaging data.
      The main algorithm behind ImageBee is a matrix factorisation approach. Motivated
      by a data-specific, non-negative mixture model, the algorithm aims to select the
      generating extreme vectors of a convex cone that contains the data. It
      approximates the movie matrix by non-negative combinations of the extreme
      vectors. These correspond to pure glomerular signals that are not mixed with
      neighbour signals. RESULTS: Evaluation shows that the proposed algorithm can
      identify the relevant biological signals on imaging data from the honeybee AL, as
      well as it can recover implanted source signals from artificial data.
      CONCLUSIONS: ImageBee enables automated data processing and visualisation for
      optical imaging data from the insect AL. The modular implementation for KNIME
      offers a flexible platform for data analysis projects, where modules can be
      rearranged or added depending on the particular application. AVAILABILITY:
      ImageBee can be installed via the KNIME update service. Installation instructions
      are available at http://tech.knime.org/imagebee-analysing-imaging-data-from-the
      honeybee-brain.

PMID- 24564240
TI  - Bioinspired insights into silicic acid stabilization mechanisms: the dominant
      role of polyethylene glycol-induced hydrogen bonding.
AB  - Mono- and disilicic acids were stabilized by uncharged polyethylene glycols
      (PEGs) in silica-supersaturated solutions (the starting solution contained 500
      ppm/8.3 mM sodium orthosilicate, Na2SiO3.5H2O, expressed as SiO2) at pH = 7, most
      likely by hydrogen bonding between the silanol groups and -CH2-CH2-O-ether
      moieties. The stabilization was monitored by measuring molybdate-reactive silica
      and also by a combination of liquid- and solid-state (29)Si NMR spectroscopy. It
      depends on PEG concentration (20-100 ppm) and molecular weight (1550-20,000 Da).
      Two narrow (29)Si NMR signals characteristic for monosilicic acid (Q(0)) and
      disilicic acid (Q(1)) can be observed in (29)Si NMR spectra of solutions
      containing PEG 10000 with intensities distinctly higher than the control, that
      is, in the absence of PEG. Silica-containing precipitates are observed in the
      presence of PEG, in contrast to the gel formed in the absence of PEG. These
      precipitates exhibit similar degrees of silica polycondensation as found in the
      gel as can be seen from the (29)Si MAS NMR spectra. However, the (2)D HETCOR
      spectra show different (1)H NMR signal shifts: The signal due to H-bonded
      SiOH/H2O, which is found at 6 ppm in the control, is shifted to ~7 ppm in the PEG
      containing precipitate. This indicates the formation of slightly stronger H-bonds
      than in the control sample, most likely between PEG and the silica species. The
      presence of PEG in these precipitates is unequivocally proven by (13)C CP MAS NMR
      spectroscopy. The (13)C signal of PEG significantly shifts and is much narrower
      in the precipitates as compared to the pristine PEG, indicating that PEG is
      embedded into the silica or at least bound to its surface (or both), and not
      phase separated. FT-IR spectra corroborate the above arguments. The H-bonding
      between silanol and ethereal O perturbs the band positions attributed to
      vibrations involving the O atom. This work may invoke an alternative way to
      envision silica species stabilization (prior to biosilica formation) in diatoms
      by investigating possible scenarios of uncharged biomacromolecules playing a role
      in biosilica synthesis.

PMID- 24564242
TI  - The neuropsychology of attention: revisiting the "Mirsky model".
AB  - Nearly 25 years ago, Mirsky and colleagues proposed a multiple-component model of
      attention. It was proposed that attention was characterized by several distinct
      elements that were organized into a system. A putative neuroanatomical substrate
      of this model of attention was proposed. This functional anatomy was primarily
      based upon inferences derived from brain lesion studies. Mirsky and colleagues
      developed a systematic clinical evaluation of this model by applying a group of
      neuropsychological tests. Since the introduction of what has been commonly
      referred to as the "Mirsky model," significant advances have been made in our
      understanding of brain-behavior relationships. This article applies current
      neuroscientific principles to "update" our understanding of attention and the
      "Mirsky model." We also demonstrate how the interpretation of neuropsychological
      tests can be modified according to principles of large-scale brain systems and
      patterns of brain network functional connectivity. 

PMID- 24564243
TI  - Neuro-critical care: a valuable placement during foundation and early
      neurosurgical training.
AB  - INTRODUCTION: Neurosciences critical care units (NCCUs) present a unique
      opportunity to junior trainees in neurosurgery as well as foundation trainees
      looking to gain experience in the management of critically ill patients with
      neurological conditions. Placements in NCCUs are undertaken in the early years of
      neurosurgical training or during neurosciences themed foundation programmes. We
      sought to quantify the educational benefits of such placements from the trainee
      perspective. METHODS: Thirty-two trainees who had undertaken placements at
      Foundation Year 2 (FY2) to Specialty Trainee Year 3 (ST3) level between August
      2009 and April 2013 were invited to take part in an online questionnaire survey.
      Competence in individual skills was self-rated on a ranked scale from one (never
      observed) to five (performed unsupervised) both before and after the placement.
      Trainees were also asked a series of questions pertaining to their ability to
      manage common neurosurgical conditions, as well as the perceived educational
      rigour of their placement. RESULTS: Twenty-three responses were received.
      Eighteen responses were from FY2s and seven were from ST1-3 level trainees.
      Following their placements, 100% of respondents felt better equipped to deal with
      neurosurgical and neurological emergencies and cranial trauma. Most felt better
      equipped to manage hydrocephalus (95.7%), polytrauma patients (95.7%),
      spontaneous intracranial haemorrhage (91.3%) and spinal trauma (82.6%).
      Significant increases were seen in experience in all practical skills assessed.
      These included central venous catheterisation (p < 0.001), intracranial pressure
      (ICP) bolt insertion (p < 0.001), ICP bolt removal (p < 0.001), external
      ventricular drain (EVD) insertion (p = 0.001) and tapping of EVD for
      cerebrospinal fluid sample (p < 0.001). CONCLUSION: Our results clearly
      demonstrate the educational benefits of NCCU placements in the early stages of a
      neurosurgical training programme as well as in the Foundation Programme. This
      supports the incorporation of a four- to six-month NCCU rotation in early years
      training as educationally valuable.

PMID- 24564241
TI  - Analysis of schizophrenia and hepatocellular carcinoma genetic network with
      corresponding modularity and pathways: novel insights to the immune system.
AB  - BACKGROUND: Schizophrenic patients show lower incidences of cancer, implicating
      schizophrenia may be a protective factor against cancer. To study the genetic
      correlation between the two diseases, a specific PPI network was constructed with
      candidate genes of both schizophrenia and hepatocellular carcinoma. The network,
      designated schizophrenia-hepatocellular carcinoma network (SHCN), was analysed
      and cliques were identified as potential functional modules or complexes. The
      findings were compared with information from pathway databases such as KEGG,
      Reactome, PID and ConsensusPathDB. RESULTS: The functions of mediator genes from
      SHCN show immune system and cell cycle regulation have important roles in the
      eitology mechanism of schizophrenia. For example, the over-expressing
      schizophrenia candidate genes, SIRPB1, SYK and LCK, are responsible for signal
      transduction in cytokine production; immune responses involving IL-2 and TREM
      1/DAP12 pathways are relevant for the etiology mechanism of schizophrenia. Novel
      treatments were proposed by searching the target genes of FDA approved drugs with
      genes in potential protein complexes and pathways. It was found that Vitamin A,
      retinoid acid and a few other immune response agents modulated by RARA and LCK
      genes may be potential treatments for both schizophrenia and hepatocellular
      carcinoma. CONCLUSIONS: This is the first study showing specific mediator genes
      in the SHCN which may suppress tumors. We also show that the schizophrenic
      protein interactions and modulation with cancer implicates the importance of
      immune system for etiology of schizophrenia.

PMID- 24564244
TI  - Fracture through fused cervical segments following trauma in a patient with
      Klippel-Feil syndrome.
AB  - Klippel-Feil syndrome (KPS) is a congenital spinal deformity characterised by the
      presence of at least one fused cervical segment. We report an unusual case of a
      fracture through fused cervical segment in a patient with KPS, who presented with
      quadriparesis and progressed on to develop respiratory failure and quadriplegia
      and who had a successful outcome following surgery. To the best of our knowledge,
      fracture through fused cervical segments in a Klippel-Feil patient has not been
      reported previously and this case report extends the spectrum of injuries seen in
      patients with KPS.

PMID- 24564245
TI  - Mycophenolate mofetil and sirolimus in hepatocyte transplantation in an
      experimental model of toxic acute liver failure.
AB  - INTRODUCTION: Hepatocyte transplantation is proposed as a solution for liver
      failure. The allotransplantation of hepatocytes has been studied extensively,
      however, graft rejection remains a major problem. The aim of the present study
      was to evaluate the immunosuppressive activity of mycophenolate mofetil (MMF),
      sirolimus, and their combination in an experimental model of hepatocyte
      allotransplantation in rats with acute liver failure. MATERIALS AND METHODS: Five
      male Wistar rats were used as hepatocyte donors and 60 male Lewis rats as
      recipients. The recipients were divided into five groups of 12 animals each.
      Group 1: no treatment. Group 2: cyclosporine. Group 3: sirolimus. Group 4: MMF.
      Group 5: MMF and sirolimus. All surviving animals were preserved for 15 days. For
      the induction of acute liver failure the recipients were injected with N-dimethyl
      nitrosamine 24 hr before transplantation. The isolated hepatocytes were
      transplanted intrasplenically. RESULTS: Analysis of the results showed a
      statistically significant prolongation of animal survival for groups 3, 4, and 5.
      More animals in group 5 survived than those in groups 3 and 4, although the
      difference was not statistically significant. Transplant hepatocyte survival was
      significantly better in groups 3, 4, and 5. Hepatocytes transplanted in the
      spleen of animals of group 5 showed better survival compared with those of groups
      3 and 4. CONCLUSION: Use of MMF and sirolimus, as monotherapy or in combination,
      is both effective and safe as immunosuppressive treatment in hepatocyte
      transplantation, as was proven in this experimental protocol.

PMID- 24564246
TI  - An examination of the effectiveness of video modelling intervention using a
      speech-generating device in preschool children at risk for autism.
AB  - OBJECTIVE: To investigate whether preschool children at risk for autism would
      learn to request a preferred object using a speech-generating device (SGD)
      following a video modelling (VM) intervention and generalize requesting
      behaviours to preferred objects across stimuli and communication partners.
      METHOD: A single-subject multiple baseline design across participants (n = 3) was
      used to assess the effects of VM intervention on requesting behaviour.
      Intervention consisted of having each participant view a VM of two adults
      demonstrating the requesting of a preferred object using the SGD. Additionally, a
      least-to-most-prompting technique was employed to facilitate the production of a
      correct response. RESULTS: All three participants demonstrated the ability to
      request preferred objects following the intervention and were able to generalize
      the newly acquired requesting behaviour across stimuli and people. CONCLUSIONS:
      Study findings indicate that a VM treatment package is effective in facilitating
      communication in children with little or no functional speech.

PMID- 24564247
TI  - Family concordance and gender differences in parent-child structured interaction
      at 12 months.
AB  - This observational study examined family concordance and gender differences in
      early parent-child interaction in the family supportive sociopolitical context of
      Norway. Mothers and fathers from 39 Norwegian families were observed on separate
      occasions with their 12-month-old children (20 girls and 19 boys). Data were
      recorded from observations using microsocial coding methodology based on social
      interaction learning theory. We found no within-family concordance between
      mothers' and fathers' behaviors with their child. The children's negative
      engagement with each parent was moderately correlated. For parents with boys,
      fathers were overall more positively engaged than mothers. Moreover, fathers of
      boys displayed more positive engagement than those of girls, whereas mothers of
      girls and boys displayed similar levels of positive engagement. In contrast to
      previous findings, mothers did not verbalize more than fathers. Girls were
      overall more positively engaged during interaction with both mothers and fathers
      than boys. Thus, in a sociopolitical context that facilitates early parent-child
      relationships and gender equality, there were few but noteworthy gender
      differences in parent-child interaction at 12 months.

PMID- 24564248
TI  - Room-temperature chemoselective reduction of nitro groups using non-noble metal
      nanocatalysts in water.
AB  - Purely aqueous-phase chemoselective reduction of a wide range of aromatic and
      aliphatic nitro substrates has been performed in the presence of inexpensive Ni-
      and Co-based nanoparticle catalysts using hydrazine hydrate as a reducing agent
      at room temperature. Along with the observed high conversions and selectivities,
      the studied nanoparticle catalysts also exhibit a high tolerance to other highly
      reducible groups present in the nitro substrates. The development of these
      potential chemoselective reduction catalysts also provides a facile route for the
      synthesis of other industrially important fine chemicals or biologically
      important compounds, where other highly reducible groups are present in close
      proximity to the targeted nitro groups. 

PMID- 24564249
TI  - Integrated Bio-Search: challenges and trends for the integration, search and
      comprehensive processing of biological information.
AB  - Many efforts exist to design and implement approaches and tools for data capture,
      integration and analysis in the life sciences. Challenges are not only the
      heterogeneity, size and distribution of information sources, but also the danger
      of producing too many solutions for the same problem. Methodological,
      technological, infrastructural and social aspects appear to be essential for the
      development of a new generation of best practices and tools. In this paper, we
      analyse and discuss these aspects from different perspectives, by extending some
      of the ideas that arose during the NETTAB 2012 Workshop, making reference
      especially to the European context. First, relevance of using data and software
      models for the management and analysis of biological data is stressed. Second,
      some of the most relevant community achievements of the recent years, which
      should be taken as a starting point for future efforts in this research domain,
      are presented. Third, some of the main outstanding issues, challenges and trends
      are analysed. The challenges related to the tendency to fund and create large
      scale international research infrastructures and public-private partnerships in
      order to address the complex challenges of data intensive science are especially
      discussed. The needs and opportunities of Genomic Computing (the integration,
      search and display of genomic information at a very specific level, e.g. at the
      level of a single DNA region) are then considered. In the current data and
      network-driven era, social aspects can become crucial bottlenecks. How these may
      best be tackled to unleash the technical abilities for effective data integration
      and validation efforts is then discussed. Especially the apparent lack of
      incentives for already overwhelmed researchers appears to be a limitation for
      sharing information and knowledge with other scientists. We point out as well how
      the bioinformatics market is growing at an unprecedented speed due to the impact
      that new powerful in silico analysis promises to have on better diagnosis,
      prognosis, drug discovery and treatment, towards personalized medicine. An open
      business model for bioinformatics, which appears to be able to reduce undue
      duplication of efforts and support the increased reuse of valuable data sets,
      tools and platforms, is finally discussed.

PMID- 24564250
TI  - libgapmis: extending short-read alignments.
AB  - BACKGROUND: A wide variety of short-read alignment programmes have been published
      recently to tackle the problem of mapping millions of short reads to a reference
      genome, focusing on different aspects of the procedure such as time and memory
      efficiency, sensitivity, and accuracy. These tools allow for a small number of
      mismatches in the alignment; however, their ability to allow for gaps varies
      greatly, with many performing poorly or not allowing them at all. The seed-and
      extend strategy is applied in most short-read alignment programmes. After
      aligning a substring of the reference sequence against the high-quality prefix of
      a short read--the seed--an important problem is to find the best possible
      alignment between a substring of the reference sequence succeeding and the
      remaining suffix of low quality of the read--extend. The fact that the reads are
      rather short and that the gap occurrence frequency observed in various studies is
      rather low suggest that aligning (parts of) those reads with a single gap is in
      fact desirable. RESULTS: In this article, we present libgapmis, a library for
      extending pairwise short-read alignments. Apart from the standard CPU version, it
      includes ultrafast SSE- and GPU-based implementations. libgapmis is based on an
      algorithm computing a modified version of the traditional dynamic-programming
      matrix for sequence alignment. Extensive experimental results demonstrate that
      the functions of the CPU version provided in this library accelerate the
      computations by a factor of 20 compared to other programmes. The analogous SSE-
      and GPU-based implementations accelerate the computations by a factor of 6 and
      11, respectively, compared to the CPU version. The library also provides the user
      the flexibility to split the read into fragments, based on the observed gap
      occurrence frequency and the length of the read, thereby allowing for a variable,
      but bounded, number of gaps in the alignment. CONCLUSIONS: We present libgapmis,
      a library for extending pairwise short-read alignments. We show that libgapmis is
      better-suited and more efficient than existing algorithms for this task. The
      importance of our contribution is underlined by the fact that the provided
      functions may be seamlessly integrated into any short-read alignment pipeline.
      The open-source code of libgapmis is available at http://www.exelixis
      lab.org/gapmis.

PMID- 24564251
TI  - A novel in silico reverse-transcriptomics-based identification and blood-based
      validation of a panel of sub-type specific biomarkers in lung cancer.
AB  - Lung cancer accounts for the highest number of cancer-related deaths worldwide.
      Early diagnosis significantly increases the disease-free survival rate and a
      large amount of effort has been expended in screening trials and the development
      of early molecular diagnostics. However, a gold standard diagnostic strategy is
      not yet available. Here, based on miRNA expression profile in lung cancer and
      using a novel in silico reverse-transcriptomics approach, followed by analysis of
      the interactome; we have identified potential transcription factor (TF) markers
      that would facilitate diagnosis of subtype specific lung cancer. A subset of
      seven TF markers has been used in a microarray screen and was then validated by
      blood-based qPCR using stage-II and IV non-small cell lung carcinomas (NSCLC).
      Our results suggest that overexpression of HMGA1, E2F6, IRF1, and TFDP1 and
      downregulation or no expression of SUV39H1, RBL1, and HNRPD in blood is suitable
      for diagnosis of lung adenocarcinoma and squamous cell carcinoma sub-types of
      NSCLC. Here, E2F6 was, for the first time, found to be upregulated in NSCLC blood
      samples. The miRNA-TF-miRNA interaction based molecular mechanisms of these seven
      markers in NSCLC revealed that HMGA1 and TFDP1 play vital roles in lung cancer
      tumorigenesis. The strategy developed in this work is applicable to any other
      cancer or disease and can assist in the identification of potential biomarkers. 

PMID- 24564252
TI  - Can we accurately report PTEN status in advanced colorectal cancer?
AB  - BACKGROUND: Loss of phosphatase and tensin homologue (PTEN) function evaluated by
      loss of PTEN protein expression on immunohistochemistry (IHC) has been reported
      as both prognostic in metastatic colorectal cancer and predictive of response to
      anti-EGFR monoclonal antibodies although results remain uncertain. Difficulties
      in the methodological assessment of PTEN are likely to be a major contributor to
      recent conflicting results. METHODS: We assessed loss of PTEN function in 51
      colorectal cancer specimens using Taqman(r) copy number variation (CNV) and IHC.
      Two blinded pathologists performed independent IHC assessment on each specimen
      and inter-observer variability of IHC assessment and concordance of IHC versus
      Taqman(r) CNV was assessed. RESULTS: Concordance between pathologists (PTEN loss
      vs no loss) on IHC assessment was 37/51 (73%). In specimens with concordant IHC
      assessment, concordance between IHC and Taqman(r) copy number in PTEN loss
      assessment was 25/37 (68%). CONCLUSION: Assessment PTEN loss in colorectal cancer
      is limited by the inter-observer variability of IHC, and discordance of CNV with
      loss of protein expression. An understanding of the genetic mechanisms of PTEN
      loss and implementation of improved and standardized methodologies of PTEN
      assessment are required to clarify the role of PTEN as a biomarker in colorectal
      cancer.

PMID- 24564254
TI  - A peptide-based nanofibrous hydrogel as a promising DNA nanovector for optimizing
      the efficacy of HIV vaccine.
AB  - This report shows that a nanovector composed of peptide-based nanofibrous
      hydrogel can condense DNA to result in strong immune responses against HIV. This
      nanovector can strongly activate both humoral and cellular immune responses to a
      balanced level rarely reported in previous studies, which is crucial for HIV
      prevention and therapy. In addition, this nanovector shows good biosafety in
      vitro and in vivo. Detailed characterizations show that the nanofibrous structure
      of the hydrogel is critical for the dramatically improved immune responses
      compared to existing materials. This peptide-based nanofibrous hydrogel shows
      great potential for efficacious HIV DNA vaccines and can be potentially used for
      delivering other vaccines and drugs. 

PMID- 24564255
TI  - Aggressive behavior as a rare side effect of subthalamic stimulation in
      Parkinson's disease.
AB  - Although deep brain stimulation (DBS) has a well-established position in the
      treatment of Parkinson's disease (PD), it may be accompanied by different side
      effects including behavioral changes. We present a patient with advanced PD after
      bilateral stimulation of the subthalamic nucleus (STN) who developed attacks of
      aggressive behavior. The patient with a 12 year history of PD underwent the
      procedure of DBS with one-stage bilateral stereotactic approach using the Leksel
      G stereotactic frame. For STN identification microrecording technique was applied
      (5 microelectrodes). Four weeks after surgery STN stimulation was switched on.
      With increasing the amplitude of stimulation on the right (active contacts 1 and
      2) the patient experienced transient episodes of aggression. Change of
      stimulation mode led to withdrawal of all side effects. We hypothesize that
      aggression episodes in the patient were caused by stimulation of limbic circuit
      probable within STN although we cannot exclude simultaneous stimulation of
      neighboring structures. Aggression episodes are rare side effect of STN-DBS,
      nevertheless they may be expected in more posteromedial placement of the
      electrode within STN. The presented case extends the evidence for non-motor
      functions of STN and highlights its role as an integrating structure within the
      basal ganglia system. 

PMID- 24564253
TI  - Identification of putative TAL effector targets of the citrus canker pathogens
      shows functional convergence underlying disease development and defense response.
AB  - BACKGROUND: Transcriptional activator-like (TAL) effectors, formerly known as the
      AvrBs3/PthA protein family, are DNA-binding effectors broadly found in
      Xanthomonas spp. that transactivate host genes upon injection via the bacterial
      type three-secretion system. Biologically relevant targets of TAL effectors, i.e.
      host genes whose induction is vital to establish a compatible interaction, have
      been reported for xanthomonads that colonize rice and pepper; however, citrus
      genes modulated by the TAL effectors PthA"s" and PthC"s" of the citrus canker
      bacteria Xanthomonas citri (Xc) and Xanthomonas aurantifolii pathotype C (XaC),
      respectively, are poorly characterized. Of particular interest, XaC causes canker
      disease in its host lemon (Citrus aurantifolia), but triggers a defense response
      in sweet orange. RESULTS: Based on, 1) the TAL effector-DNA binding code, 2) gene
      expression data of Xc and XaC-infiltrated sweet orange leaves, and 3) citrus
      hypocotyls transformed with PthA2, PthA4 or PthC1, we have identified a
      collection of Citrus sinensis genes potentially targeted by Xc and XaC TAL
      effectors. Our results suggest that similar with other strains of Xanthomonas TAL
      effectors, PthA2 and PthA4, and PthC1 to some extent, functionally converge. In
      particular, towards induction of genes involved in the auxin and gibberellin
      synthesis and response, cell division, and defense response. We also present
      evidence indicating that the TAL effectors act as transcriptional repressors and
      that the best scoring predicted DNA targets of PthA"s" and PthC"s" in citrus
      promoters predominantly overlap with or localize near to TATA boxes of core
      promoters, supporting the idea that TAL effectors interact with the host basal
      transcriptional machinery to recruit the RNA pol II and start transcription.
      CONCLUSIONS: The identification of PthA"s" and PthC"s" targets, such as the LOB
      (lateral organ boundary) and CCNBS genes that we report here, is key for the
      understanding of the canker symptoms development during host susceptibility, or
      the defenses of sweet orange against the canker bacteria. We have narrowed down
      candidate targets to a few, which pointed out the host metabolic pathways
      explored by the pathogens.

PMID- 24564256
TI  - Development and validation of an algorithm to identify patients newly diagnosed
      with HIV infection from electronic health records.
AB  - An algorithm was developed that identifies patients with new diagnoses of HIV
      infection by the use of electronic health records. It was based on the sequence
      of HIV diagnostic tests, entry of ICD-9-CM diagnostic codes, and measurement of
      HIV-1 plasma RNA levels in persons undergoing HIV testing from 2006 to 2012 at
      four large urban Veterans Health Administration (VHA) facilities. Source data
      were obtained from the VHA National Corporate Data Warehouse. Chart review was
      done by a single trained abstractor to validate site-level data regarding new
      diagnoses. We identified 1,153 patients as having a positive HIV diagnostic test
      within the VHA. Of these, 57% were determined to have prior knowledge of their
      HIV status from testing at non-VHA facilities. An algorithm based on the sequence
      and results of available laboratory tests and ICD-9-CM entries identified new HIV
      diagnoses with a sensitivity of 83%, specificity of 86%, positive predictive
      value of 85%, and negative predictive value of 90%. There were no meaningful
      demographic or clinical differences between newly diagnosed patients who were
      correctly or incorrectly classified by the algorithm. We have validated a method
      to identify cases of new diagnosis of HIV infection in large administrative
      datasets. This method, which has a sensitivity of 83%, specificity of 86%,
      positive predictive value of 85%, and negative predictive value of 90% can be
      used in analyses of the epidemiology of newly diagnosed HIV infection.

PMID- 24564258
TI  - Staphylococcus aureus induces apoptosis in primary bovine mammary epithelial
      cells through Fas-FADD death receptor-linked caspase-8 signaling.
AB  - Infections with Staphylococcus aureus, a common inducer of mastitis, often result
      in mammary gland damage and death of various cell types. Although S. aureus was
      suggested to induce apoptosis in a bovine mammary epithelial cell (BMEC) line,
      MAC-T, it is unknown whether primary BMECs (pBMECs) apoptosis is triggered by S.
      aureus and the associated underlying molecular mechanisms have not been
      determined. Here, we demonstrated that S. aureus induced apoptosis in pBMECs in a
      time- and dose-dependent manner. Further, S. aureus-induced apoptosis in pBMECs
      was associated with activation of caspase-3 and caspase-8, but caspase-9 was not.
      In addition, pBMECs apoptosis was mitigated by caspase-3 and caspase-8
      inhibitors, suggesting that apoptosis is initiated via caspase-8 activation.
      Moreover, S. aureus infection significantly increased expressions of Fas and Fas
      associated death domain (FADD) of pBMECs. Taken together, our results
      demonstrated that S. aureus induced apoptosis in pBMECs via the Fas-FADD death
      receptor and subsequently triggered the caspase-8-dependent signaling.

PMID- 24564257
TI  - Fast algorithms and heuristics for phylogenomics under ILS and hybridization.
AB  - BACKGROUND: Phylogenomic analyses involving whole-genome or multi-locus data
      often entail dealing with incongruent gene trees. In this paper, we consider two
      causes of such incongruence, namely, incomplete lineage sorting (ILS) and
      hybridization, and consider both parsimony and probabilistic criteria for dealing
      with them. RESULTS: Under the assumption of ILS, computing the probability of a
      gene tree given a species tree is a very hard problem. We present a heuristic for
      speeding up the computation, and demonstrate how it scales up computations to
      data sizes that are not feasible to analyze using current techniques, while
      achieving very good accuracy. Further, under the assumption of both ILS and
      hybridization, computing the probability of a gene tree and parsimoniously
      reconciling it with a phylogenetic network are both very hard problems. We
      present two exact algorithms for these two problems that speed up existing
      techniques significantly and enable analyses of much larger data sets than is
      currently feasible. CONCLUSION: Our heuristics and algorithms enable phylogenomic
      analyses of larger (in terms of numbers of taxa) data sets than is currently
      feasible. Further, our methods account for ILS and hybridization, thus allowing
      analyses of reticulate evolutionary histories.

PMID- 24564259
TI  - How within-country inequalities and co-coverage may affect LiST estimates of
      lives saved by scaling up interventions.
AB  - Lives-saved estimates calculated by LiST include the implicit assumptions that
      there are no inequalities among different socioeconomic groups, and also that the
      likelihood of a mother or child receiving a given intervention is independent
      from the probability of receiving any other interventions. It is reasonable to
      assume that, as a consequence of these assumptions, LiST estimates may exaggerate
      the numbers of lives saved in a population, by ignoring the fact that coverage is
      likely to be lower and mortality higher among the poor than the rich, and also by
      failing to take into account that coverage with different interventions may be
      clustered at individual mothers and children--a phenomenon described as co
      coverage. We used data from 127 DHS surveys to estimate how much these two
      assumptions may bias estimates produced by LiST, and conclude that under real
      life conditions bias occurred in both directions, with LiST results either over
      or underestimating the more complex estimates. With few exceptions, bias tended
      to be small (less than 10% in either direction).

PMID- 24564261
TI  - Validation of an automated wireless system for sleep monitoring during daytime
      naps.
AB  - An automated wireless system (WS) for sleep monitoring was recently developed and
      validated for assessing nighttime sleep. Here, we aimed to evaluate the validity
      of the WS to correctly monitor daytime sleep during naps compared to
      polysomnography (PSG). We found that the WS underestimated wake, sleep onset
      latency, and wake after sleep onset. Meanwhile, it overestimated total sleep
      time, sleep efficiency, and duration of REM sleep. Sensitivity was moderate for
      wake (58.51%) and light sleep (66.92%) and strong for deep sleep (83.46%) and REM
      sleep (82.12%). These results demonstrated that the WS had a low ability to
      detect wake and systematically overscored REM sleep, implicating the WS as an
      inadequate substitute for PSG in diagnosing sleep disorders or for research in
      which sleep staging is essential. 

PMID- 24564260
TI  - Microdistribution of the resistance of malaria vectors to deltamethrin in the
      region of Plateau (southeastern Benin) in preparation for an assessment of the
      impact of resistance on the effectiveness of Long Lasting Insecticidal Nets
      (LLINs).
AB  - BACKGROUND: This study aims to research two areas, one with a resistant and the
      other with a susceptible profile of An. gambiae to deltamethrin in the region of
      Plateau (southern Benin). In each area, eight localities were sought. Both areas
      were needed for the assessment of the impact of malaria vector resistance to
      pyrethroids on the effectiveness of Long Lasting Insecticidal Nets (LLINs). The
      susceptible area of An. gambiae to deltamethrin was used as a control. METHODS:
      In total, 119 localities in the region of Plateau were screened by sampling An.
      gambiae s.l larvae. Female mosquitoes resulting from these larvae were exposed to
      0.05% deltamethrin following WHO standards. PCR was used to identify species and
      molecular forms of the dead and alive mosquitoes. Finally, we identified kdr
      mutations (1014 F and 1014S) using the HOLA technique. RESULTS: Fifty-six out of
      119 prospected localities tested positive for Anopheles gambae s.l breeding
      sites. The results showed that An. gambiae was resistant to deltamethrin in 39
      localities and susceptible in only 2 localities; resistance to deltamethrin was
      suspected in 15 localities. The HOLA technique confirmed the presence of kdr 1014
      F mutation and the absence of kdr 1014S mutation. The kdr 1014 F mutation was
      found in both M and S molecular forms at relatively high frequencies therefore
      confirming the susceptibility tests. CONCLUSION: We were unable to identify the
      eight susceptible areas due to the overall resistance of An. gambiae to
      deltamethrin in the region of Plateau. To implement the study, we kept two areas,
      one with high resistance (R+++) and the other with low resistance (R+) of An.
      gambiae to deltamethrin.

PMID- 24564263
TI  - Wholly pi-conjugated low-molecular-weight organogelator that displays triple
      channel responses to fluoride ions.
AB  - A novel salicylidene aniline-based wholly pi-conjugated molecule that could be
      self-assembled into an organogel was synthesized. The rigid organogel collapsed
      into fluid solutions with significant changes in UV-vis absorption and
      fluorescence colors in response to fluoride ions. It was found that the hydroxyl
      group in the salicylidene aniline moiety played a key role not only in the
      gelation but also in fluoride ion responses. 

PMID- 24564262
TI  - Impact of isolated systolic hypertension on normalization of left ventricular
      structure during antihypertensive treatment (the LIFE study).
AB  - OBJECTIVE: We tested the impact of isolated systolic hypertension (ISH) on
      normalization of left ventricular (LV) structure during antihypertensive
      treatment. METHODS: Baseline and annual echocardiograms were recorded in 873
      hypertensive patients with electrocardiographic signs of LV hypertrophy during
      4.8 years randomized losartan- or atenolol-based antihypertensive treatment in
      the Losartan Intervention For Endpoint (LIFE) reduction in hypertension study and
      classified as having ISH (n = 128) if systolic BP >= 160 mmHg and diastolic BP <
      90 mmHg, or non-ISH divided into two groups by systolic BP >= 160 mmHg (non-ISH
      >= 160 mmHg) (n = 645) and systolic BP < 160 mm Hg (n = 100) (non-ISH < 160
      mmHg), respectively. RESULTS: Patients with ISH were older, with higher
      prevalence of diabetes than non-ISH groups and higher pulse pressure/stroke
      volume index (all p < 0.05). Baseline systolic blood pressure (BP) differed
      between groups and was highest in the non-ISH >= 160 mmHg group (p < 0.05).
      Systolic BP reduction was less in the ISH group (p < 0.05). LV geometry did not
      differ between ISH and non-ISH >= 160 mmHg groups at baseline, but ISH had more
      residual LV hypertrophy of concentric type at the last study visit (p < 0.05). In
      multivariate analysis, less reduction of LV mass was predicted by ISH (beta = -
      0.07) independent of significant associations with baseline LVMi (beta = 0.52)
      and atenolol-based treatment (beta = - 0.08) and clinical confounders (all p <
      0.05). CONCLUSIONS: ISH is associated with impaired normalization of LV mass
      during systematic antihypertensive treatment. The findings may help explain the
      higher cardiovascular event rate previously reported in ISH patients.

PMID- 24564265
TI  - Exploring the feasibility of the visual language in autism program for children
      in an early intervention group setting: views of parents, educators, and health
      professionals.
AB  - OBJECTIVE: To explore the views of key stakeholders on using visual supports for
      children with developmental disabilities in early intervention group settings.
      Specifically, this study aimed to determine stakeholders' views on the barriers
      to and facilitators for the use of visual supports in these settings to inform
      the feasibility of implementing an immersive Visual Language in Autism program.
      METHODS: This study involved three focus groups of parents, educators, and health
      professionals at one Australian early intervention group setting. RESULTS: Lack
      of time, limited services, negative attitudes in society, and inconsistent use
      were cited as common barriers to using visual supports. Facilitators included
      having access to information and evidence on visual supports, increased awareness
      of visual supports, and the use of mobile technologies. CONCLUSION: The Visual
      Language in Autism program is feasible in early intervention group settings, if
      barriers to and facilitators for its use are addressed to enable an immersive
      visual language experience.

PMID- 24564264
TI  - Uniting cheminformatics and chemical theory to predict the intrinsic aqueous
      solubility of crystalline druglike molecules.
AB  - We present four models of solution free-energy prediction for druglike molecules
      utilizing cheminformatics descriptors and theoretically calculated thermodynamic
      values. We make predictions of solution free energy using physics-based theory
      alone and using machine learning/quantitative structure-property relationship
      (QSPR) models. We also develop machine learning models where the theoretical
      energies and cheminformatics descriptors are used as combined input. These models
      are used to predict solvation free energy. While direct theoretical calculation
      does not give accurate results in this approach, machine learning is able to give
      predictions with a root mean squared error (RMSE) of ~1.1 log S units in a 10
      fold cross-validation for our Drug-Like-Solubility-100 (DLS-100) dataset of 100
      druglike molecules. We find that a model built using energy terms from our
      theoretical methodology as descriptors is marginally less predictive than one
      built on Chemistry Development Kit (CDK) descriptors. Combining both sets of
      descriptors allows a further but very modest improvement in the predictions.
      However, in some cases, this is a statistically significant enhancement. These
      results suggest that there is little complementarity between the chemical
      information provided by these two sets of descriptors, despite their different
      sources and methods of calculation. Our machine learning models are also able to
      predict the well-known Solubility Challenge dataset with an RMSE value of 0.9-1.0
      log S units.

PMID- 24564266
TI  - Comparison of analgesic effects of remifentanil and fentanyl NCA after pediatric
      cardiac surgery.
AB  - The purpose of this study was to compare the analgesic effects of remifentanil
      with fentanyl following pediatric cardiac surgery. Fifty patients were included
      in the study and were randomized into two groups. Patients in group R were given
      remifentanil (50 MUg/ml) at an infusion rate of 0.07 MUg/kg/min and with bolus
      doses of 0.25 MUg/kg with a 5-min lockout time; group F patients received
      fentanyl (50 MUg/ml) at an infusion rate of 0.1 MUg/kg/min and with bolus doses
      of 1 MUg/kg with a 5-min lockout time. Pain was assessed using the Face, Legs,
      Activity, Cry, Consolability scale (FLACC scale), and sedation was assessed using
      the Ramsay sedation score. The number of boluses and demands, time to extubation,
      and side effects were analyzed. The FLACC scale, Ramsay sedation score, and mean
      extubation times were similar in the two groups. The total number of boluses and
      demands were significantly greater for group R than for group F. Itching as a
      side-effect was more severe in group F (p < .05). NCA remifentanil and fentanyl
      offer similarly effective pain control after pediatric cardiac surgery, but
      remifentanil has fewer side effects than fentanyl, indicating the suitability of
      remifentanil for use in NCA systems.

PMID- 24564267
TI  - Syntheses, structures, and electronic properties of Ba3FeUS6 and Ba3AgUS6.
AB  - The compounds Ba3FeUS6 and Ba3AgUS6 have been synthesized by the reactions of
      BaS, U, S, and M (= Fe or Ag) at 1223 K. These two isostructural compounds
      crystallize in the K4CdCl6 structure type in the trigonal system in space group
      D3d(6)-R3c. Both structures feature infinite infinity(1)[MUS6(6-)] chains along c
      that are separated by Ba atoms. The infinity(1)[FeUS6(6-)] chains are formed by
      the face-sharing of US6 trigonal prisms with FeS6 octahedra; in contrast, the
      infinity(1)[AgUS6(6-)] chains are formed by the face-sharing of US6 octahedra
      with AgS6 trigonal prisms. The Ba3FeUS6 compound charge balances with 3 Ba(2+), 1
      Fe(2+), 1 U4+, and 6 S(2-), whereas Ba3AgUS6 charge balances with 3 Ba(2+), 1
      Ag(1+), 1 U(5+), and 6 S(2-). This structure offers a remarkable flexibility in
      terms of the oxidation state of the incorporated uranium depending on the
      oxidation state of the d-block metal. DFT calculations performed with the HSE
      functional have led to band gaps of 2.3 and 2.2 eV for Ba3FeUS6 and Ba3AgUS6,
      respectively. From resistivity measurements, the Arrhenius activation energies
      are 0.12(1) and 0.43(1) eV for Ba3FeUS6 and Ba3AgUS6, respectively.

PMID- 24564268
TI  - Gene regulatory networks inference using a multi-GPU exhaustive search algorithm.
AB  - BACKGROUND: Gene regulatory networks (GRN) inference is an important
      bioinformatics problem in which the gene interactions need to be deduced from
      gene expression data, such as microarray data. Feature selection methods can be
      applied to this problem. A feature selection technique is composed by two parts:
      a search algorithm and a criterion function. Among the search algorithms already
      proposed, there is the exhaustive search where the best feature subset is
      returned, although its computational complexity is unfeasible in almost all
      situations. The objective of this work is the development of a low cost parallel
      solution based on GPU architectures for exhaustive search with a viable cost
      benefit. We use CUDATM, a general purpose parallel programming platform that
      allows the usage of NVIDIA(r) GPUs to solve complex problems in an efficient way.
      RESULTS: We developed a parallel algorithm for GRN inference based on multiple
      GPU cards and obtained encouraging speedups (order of hundreds), when assuming
      that each target gene has two multivariate predictors. Also, experiments using
      single and multiple GPUs were performed, indicating that the speedup grows almost
      linearly with the number of GPUs. CONCLUSION: In this work, we present a proof of
      principle, showing that it is possible to parallelize the exhaustive search
      algorithm in GPUs with encouraging results. Although our focus in this paper is
      on the GRN inference problem, the exhaustive search technique based on GPU
      developed here can be applied (with minor adaptations) to other combinatorial
      problems.

PMID- 24564269
TI  - Tuning the reactivity of oxygen/sulfur by acidity of the catalyst in Prins
      cyclization: oxa- versus thia-selectivity.
AB  - An unprecedented oxa- versus thia-selectivity has been observed in Prins
      cyclization of 6-mercaptohex-3-en-1-ol with aldehydes. In the presence of a
      stoichiometric amount of strong Lewis or Bronsted acids, the reaction provides
      the hexahydro-2H-thieno[3,2-c]pyran skeleton predominantly via oxonium-Prins
      cyclization. In contrast, a catalytic amount of weak Lewis or Bronsted acids
      provides the hexahydro-2H-thiopyrano[4,3-b]furan preferentially through thionium
      Prins cyclization. 

PMID- 24564270
TI  - Elucidating different mass flow direction induced polyaniline-ionic liquid
      interface properties: insight gained from DC voltammetry and impedance
      spectroscopy.
AB  - This work describes the use of direct current (DC) cyclic voltammetry (CV) and
      alternating current (AC) electrochemical impedance spectroscopy (EIS) as a means
      to monitor an electrochemical interface of different mass flow direction induced
      polyaniline (PANI) film in IL (BmimPF6). Observed by SEM, vertical mass flow
      (VMF) and horizontal mass flow (HMF) induce porous nanorod and compact granular
      morphology of PANI, respectively. The present work explores in detail analysis of
      double layer capacitance, polarization resistance, diffusion mechanism, as well
      as other electrochemical features associated with the PANI-IL interface. A
      comparatively higher value of capacitance obtained for VMF PANI film from CV
      measurement confirms the higher electroactivity at the VMF electrode than the HMF
      film. Impedance spectroscopy, using a small amplitude perturbation, confirms the
      CV result. Impedance measurement gives a value of capacitance larger than that
      from CV where the amplitude of the perturbation is much larger. The implications
      of these results for its potential application in energy storage devices are
      discussed. 

PMID- 24564271
TI  - Electron transfer kinetics in CdS nanorod-[FeFe]-hydrogenase complexes and
      implications for photochemical H2 generation.
AB  - This Article describes the electron transfer (ET) kinetics in complexes of CdS
      nanorods (CdS NRs) and [FeFe]-hydrogenase I from Clostridium acetobutylicum
      (CaI). In the presence of an electron donor, these complexes produce H2
      photochemically with quantum yields of up to 20%. Kinetics of ET from CdS NRs to
      CaI play a critical role in the overall photochemical reactivity, as the quantum
      efficiency of ET defines the upper limit on the quantum yield of H2 generation.
      We investigated the competitiveness of ET with the electron relaxation pathways
      in CdS NRs by directly measuring the rate and quantum efficiency of ET from
      photoexcited CdS NRs to CaI using transient absorption spectroscopy. This
      technique is uniquely suited to decouple CdS->CaI ET from the processes occurring
      in the enzyme during H2 production. We found that the ET rate constant (k(ET))
      and the electron relaxation rate constant in CdS NRs (k(CdS)) were comparable,
      with values of 10(7) s(-1), resulting in a quantum efficiency of ET of 42% for
      complexes with the average CaI:CdS NR molar ratio of 1:1. Given the direct
      competition between the two processes that occur with similar rates, we propose
      that gains in efficiencies of H2 production could be achieved by increasing k(ET)
      and/or decreasing k(CdS) through structural modifications of the nanocrystals.
      When catalytically inactive forms of CaI were used in CdS-CaI complexes, ET
      behavior was akin to that observed with active CaI, demonstrating that electron
      injection occurs at a distal iron-sulfur cluster and is followed by transport
      through a series of accessory iron-sulfur clusters to the active site of CaI.
      Using insights from this time-resolved spectroscopic study, we discuss the
      intricate kinetic pathways involved in photochemical H2 generation in CdS-CaI
      complexes, and we examine how the relationship between the electron injection
      rate and the other kinetic processes relates to the overall H2 production
      efficiency.

PMID- 24564272
TI  - Phase change for the accuracy of the median value in estimating divergence time.
AB  - We prove that for general models of random gene-order evolution of k >= 3
      genomes, as the number of genes n goes to infinity, the median value approximates
      k times the divergence time if the number of rearrangements is less than cn/4 for
      any c <1. For some c* >= 1, if the number of rearrangements is greater than
      c*n/4, this approximation does not hold. 

PMID- 24564273
TI  - Co-catalytic absorption layers for controlled laser-induced chemical vapor
      deposition of carbon nanotubes.
AB  - The concept of co-catalytic layer structures for controlled laser-induced
      chemical vapor deposition of carbon nanotubes is established, in which a thin Ta
      support layer chemically aids the initial Fe catalyst reduction. This enables a
      significant reduction in laser power, preventing detrimental positive optical
      feedback and allowing improved growth control. Systematic study of experimental
      parameters combined with simple thermostatic modeling establishes general
      guidelines for the effective design of such catalyst/absorption layer
      combinations. Local growth of vertically aligned carbon nanotube forests directly
      on flexible polyimide substrates is demonstrated, opening up new routes for
      nanodevice design and fabrication. 

PMID- 24564274
TI  - A base composition analysis of natural patterns for the preprocessing of
      metagenome sequences.
AB  - BACKGROUND: On the pretext that sequence reads and contigs often exhibit the same
      kinds of base usage that is also observed in the sequences from which they are
      derived, we offer a base composition analysis tool. Our tool uses these natural
      patterns to determine relatedness across sequence data. We introduce spectrum
      sets (sets of motifs) which are permutations of bacterial restriction sites and
      the base composition analysis framework to measure their proportional content in
      sequence data. We suggest that this framework will increase the efficiency during
      the pre-processing stages of metagenome sequencing and assembly projects.
      RESULTS: Our method is able to differentiate organisms and their reads or
      contigs. The framework shows how to successfully determine the relatedness
      between these reads or contigs by comparison of base composition. In particular,
      we show that two types of organismal-sequence data are fundamentally different by
      analyzing their spectrum set motif proportions (coverage). By the application of
      one of the four possible spectrum sets, encompassing all known restriction sites,
      we provide the evidence to claim that each set has a different ability to
      differentiate sequence data. Furthermore, we show that the spectrum set selection
      having relevance to one organism, but not to the others of the data set, will
      greatly improve performance of sequence differentiation even if the fragment size
      of the read, contig or sequence is not lengthy. CONCLUSIONS: We show the proof of
      concept of our method by its application to ten trials of two or three freshly
      selected sequence fragments (reads and contigs) for each experiment across the
      six organisms of our set. Here we describe a novel and computationally effective
      pre-processing step for metagenome sequencing and assembly tasks. Furthermore,
      our base composition method has applications in phylogeny where it can be used to
      infer evolutionary distances between organisms based on the notion that related
      organisms often have much conserved code.

PMID- 24564275
TI  - Structure and morphology in diffusion-driven growth of nanowires: the case of
      ZnTe.
AB  - Gold-catalyzed ZnTe nanowires were grown at low temperature by molecular beam
      epitaxy on a ZnTe(111) B buffer layer, under different II/VI flux ratios,
      including with CdTe insertions. High-resolution electron microscopy and energy
      dispersive X-ray spectroscopy (EDX) gave information about the crystal structure,
      polarity, and growth mechanisms. We observe, under stoichiometric conditions, the
      simultaneous presence of zinc-blende and wurtzite nanowires spread homogeneously
      on the same sample. Wurtzite nanowires are cylinder-shaped with a pyramidal
      structured base. Zinc-blende nanowires are cone-shaped with a crater at their
      base. Both nanowires and substrate show a Te-ended polarity. Te-rich conditions
      favor zinc-blende nanowires, while Zn-rich suppress nanowire growth. Using a
      diffusion-driven growth model, we present a criterion for the existence of a
      crater or a pyramid at the base of the nanowires. The difference in nanowire
      morphology indicates lateral growth only for zinc-blende nanowires. The role of
      the direct impinging flux on the nanowire's sidewall is discussed. 

PMID- 24564276
TI  - Context-based preprocessing of molecular docking data.
AB  - BACKGROUND: Data preprocessing is a major step in data mining. In data
      preprocessing, several known techniques can be applied, or new ones developed, to
      improve data quality such that the mining results become more accurate and
      intelligible. Bioinformatics is one area with a high demand for generation of
      comprehensive models from large datasets. In this article, we propose a context
      based data preprocessing approach to mine data from molecular docking simulation
      results. The test cases used a fully-flexible receptor (FFR) model of
      Mycobacterium tuberculosis InhA enzyme (FFR_InhA) and four different ligands.
      RESULTS: We generated an initial set of attributes as well as their respective
      instances. To improve this initial set, we applied two selection strategies. The
      first was based on our context-based approach while the second used the CFS
      (Correlation-based Feature Selection) machine learning algorithm. Additionally,
      we produced an extra dataset containing features selected by combining our
      context strategy and the CFS algorithm. To demonstrate the effectiveness of the
      proposed method, we evaluated its performance based on various predictive (RMSE,
      MAE, Correlation, and Nodes) and context (Precision, Recall and FScore) measures.
      CONCLUSIONS: Statistical analysis of the results shows that the proposed context
      based data preprocessing approach significantly improves predictive and context
      measures and outperforms the CFS algorithm. Context-based data preprocessing
      improves mining results by producing superior interpretable models, which makes
      it well-suited for practical applications in molecular docking simulations using
      FFR models.

PMID- 24564278
TI  - Explorative search of distributed bio-data to answer complex biomedical
      questions.
AB  - BACKGROUND: The huge amount of biomedical-molecular data increasingly produced is
      providing scientists with potentially valuable information. Yet, such data
      quantity makes difficult to find and extract those data that are most reliable
      and most related to the biomedical questions to be answered, which are
      increasingly complex and often involve many different biomedical-molecular
      aspects. Such questions can be addressed only by comprehensively searching and
      exploring different types of data, which frequently are ordered and provided by
      different data sources. Search Computing has been proposed for the management and
      integration of ranked results from heterogeneous search services. Here, we
      present its novel application to the explorative search of distributed biomedical
      molecular data and the integration of the search results to answer complex
      biomedical questions. RESULTS: A set of available bioinformatics search services
      has been modelled and registered in the Search Computing framework, and a
      Bioinformatics Search Computing application (Bio-SeCo) using such services has
      been created and made publicly available at
      http://www.bioinformatics.deib.polimi.it/bio-seco/seco/. It offers an integrated
      environment which eases search, exploration and ranking-aware combination of
      heterogeneous data provided by the available registered services, and supplies
      global results that can support answering complex multi-topic biomedical
      questions. CONCLUSIONS: By using Bio-SeCo, scientists can explore the very large
      and very heterogeneous biomedical-molecular data available. They can easily make
      different explorative search attempts, inspect obtained results, select the most
      appropriate, expand or refine them and move forward and backward in the
      construction of a global complex biomedical query on multiple distributed sources
      that could eventually find the most relevant results. Thus, it provides an
      extremely useful automated support for exploratory integrated bio search, which
      is fundamental for Life Science data driven knowledge discovery.

PMID- 24564277
TI  - An improved ChIP-seq peak detection system for simultaneously identifying post
      translational modified transcription factors by combinatorial fusion, using
      SUMOylation as an example.
AB  - BACKGROUND: Post-translational modification (PTM) of transcriptional factors and
      chromatin remodelling proteins is recognized as a major mechanism by which
      transcriptional regulation occurs. Chromatin immunoprecipitation (ChIP) in
      combination with high-throughput sequencing (ChIP-seq) is being applied as a gold
      standard when studying the genome-wide binding sites of transcription factor
      (TFs). This has greatly improved our understanding of protein-DNA interactions on
      a genomic-wide scale. However, current ChIP-seq peak calling tools are not
      sufficiently sensitive and are unable to simultaneously identify post
      translational modified TFs based on ChIP-seq analysis; this is largely due to the
      wide-spread presence of multiple modified TFs. Using SUMO-1 modification as an
      example; we describe here an improved approach that allows the simultaneous
      identification of the particular genomic binding regions of all TFs with SUMO-1
      modification. RESULTS: Traditional peak calling methods are inadequate when
      identifying multiple TF binding sites that involve long genomic regions and
      therefore we designed a ChIP-seq processing pipeline for the detection of peaks
      via a combinatorial fusion method. Then, we annotate the peaks with known
      transcription factor binding sites (TFBS) using the Transfac Matrix Database
      (v7.0), which predicts potential SUMOylated TFs. Next, the peak calling result
      was further analyzed based on the promoter proximity, TFBS annotation, a
      literature review, and was validated by ChIP-real-time quantitative PCR (qPCR)
      and ChIP-reChIP real-time qPCR. The results show clearly that SUMOylated TFs are
      able to be pinpointed using our pipeline. CONCLUSION: A methodology is presented
      that analyzes SUMO-1 ChIP-seq patterns and predicts related TFs. Our analysis
      uses three peak calling tools. The fusion of these different tools increases the
      precision of the peak calling results. TFBS annotation method is able to predict
      potential SUMOylated TFs. Here, we offer a new approach that enhances ChIP-seq
      data analysis and allows the identification of multiple SUMOylated TF binding
      sites simultaneously, which can then be utilized for other functional PTM binding
      site prediction in future.

PMID- 24564279
TI  - Ultrasound microbubble-mediated delivery of integrin-linked kinase gene improves
      endothelial progenitor cells dysfunction in pre-eclampsia.
AB  - Pre-eclampsia (PE) is a specific vascular complication in pregnancy whose precise
      mechanism is still unclear. We hypothesized that endothelial progenitor cells
      (EPCs), the precursor of endothelial cells, might be impaired in patients with PE
      and hold a great promise for the treatment of PE. In the present study, we
      analyzed the EPCs number and expression of integrin-linked kinase (ILK) in PE
      patients. We confirmed that both EPCs number and ILK expression were diminished
      in PE patients. Next, we transfected EPCs with ILK gene using ultrasonic
      microbubble technique (UMT) for the first time, as UMT is a novel type of gene
      transfer technology showing promising applications in stem cells apart from EPCs.
      To further investigate the transfection efficiency of UMT, RT-PCR analysis and
      western blot were used to examine the messenger RNA (mRNA) and protein level of
      ILK. After transfection of the ILK gene, EPCs function was tested to illustrate
      the role of ILK in cell proliferation, apoptosis, migration, and secretion. The
      results of the in vitro study suggested that UMT, a novel gene delivery system,
      could be considered a potent physical method for EPCs transfection. Moreover, the
      growth and angiogenetic properties of EPCs are enhanced by introducing ILK. This
      study may afford a new trend for EPCs transfection and gene therapy in PE. 

PMID- 24564280
TI  - MHC2SKpan: a novel kernel based approach for pan-specific MHC class II peptide
      binding prediction.
AB  - BACKGROUND: Computational methods for the prediction of Major Histocompatibility
      Complex (MHC) class II binding peptides play an important role in facilitating
      the understanding of immune recognition and the process of epitope discovery. To
      develop an effective computational method, we need to consider two important
      characteristics of the problem: (1) the length of binding peptides is highly
      flexible; and (2) MHC molecules are extremely polymorphic and for the vast
      majority of them there are no sufficient training data. METHODS: We develop a
      novel string kernel MHC2SK (MHC-II String Kernel) method to measure the
      similarities among peptides with variable lengths. By considering the distinct
      features of MHC-II peptide binding prediction problem, MHC2SK differs
      significantly from the recently developed kernel based method, GS (Generic
      String) kernel, in the way of computing similarities. Furthermore, we extend
      MHC2SK to MHC2SKpan for pan-specific MHC-II peptide binding prediction by
      leveraging the binding data of various MHC molecules. RESULTS: MHC2SK
      outperformed GS in allele specific prediction using a benchmark dataset, which
      demonstrates the effectiveness of MHC2SK. Furthermore, we evaluated the
      performance of MHC2SKpan using various benckmark data sets from several different
      perspectives: Leave-one-allele-out (LOO), 5-fold cross validation as well as
      independent data testing. MHC2SKpan has achieved comparable performance with
      NetMHCIIpan-2.0 and outperformed NetMHCIIpan-1.0, TEPITOPEpan and MultiRTA, being
      statistically significant. MHC2SKpan can be freely accessed at http://datamining
      iip.fudan.edu.cn/service/MHC2SKpan/index.html.

PMID- 24564281
TI  - Magnetic resonance imaging detects changes in structure and perfusion, and
      response to therapy in early cystic fibrosis lung disease.
AB  - RATIONALE: Studies demonstrating early structural lung damage in infants and
      preschool children with cystic fibrosis (CF) suggest that noninvasive monitoring
      will be important to identify patients who may benefit from early therapeutic
      intervention. Previous studies demonstrated that magnetic resonance imaging (MRI)
      detects structural and functional abnormalities in lungs from older patients with
      CF without radiation exposure. OBJECTIVES: To evaluate the potential of MRI to
      detect abnormal lung structure and perfusion in infants and preschool children
      with CF, and to monitor the response to therapy for pulmonary exacerbation.
      METHODS: MRI studies were performed in 50 children with CF (age, 3.1 +/- 2.1 yr;
      range, 0-6 yr) in stable clinical condition (n = 40) or pulmonary exacerbation
      before and after antibiotic treatment (n = 10), and in 26 non-CF control subjects
      (age, 2.9 +/- 1.9 yr). T1- and T2-weighted sequences before and after intravenous
      contrast and first-pass perfusion imaging were acquired, and assessed on the
      basis of a dedicated morphofunctional score. MEASUREMENTS AND MAIN RESULTS: MRI
      demonstrated bronchial wall thickening/bronchiectasis, mucus plugging, and
      perfusion deficits from the first year of life in most stable patients with CF
      (global score, 10.0 +/- 4.0), but not in non-CF control subjects (score, 0.0 +/-
      0.0; P < 0.001). In patients with exacerbations, the global MRI score was
      increased to 18.0 +/- 2.0 (P < 0.001), and was significantly reduced to 12.0 +/-
      3.0 (P < 0.05) after antibiotic therapy. CONCLUSIONS: MRI detected abnormalities
      in lung structure and perfusion, and response to therapy for exacerbations in
      infants and preschool children with CF. These results support the development of
      MRI for noninvasive monitoring and as an end point in interventional trials for
      early CF lung disease. Clinical trial registered with www.clinicaltrials.gov
      (NCT00760071).

PMID- 24564283
TI  - Monte Carlo simulations of thin hydrocarbon films: composition heterogeneity and
      structure at the solid-liquid and liquid-vapor interfaces.
AB  - The structural properties of 10 nm thick lubricant films consisting of binary and
      ternary n-alkane mixtures (8 <= n <= 12) adsorbed on a structureless metal
      substrate were studied for several temperatures and compositions using Monte
      Carlo simulations. Configurational-bias Monte Carlo identity switch moves are
      essential to sample the spatial distribution in these mixtures. Longer alkanes
      are found to preferentially adsorb onto the substrate while shorter alkanes are
      enriched at the liquid-vapor interface. This preferential adsorption is evident
      even when the two chains differ by only one methylene unit and the longer chain
      is the minor component. Enhanced composition heterogeneity and orientational
      ordering and fewer gauche defects are characteristic features of the first layer
      near the substrate. 

PMID- 24564282
TI  - Developmental aspects and neurobiological correlates of working and associative
      memory.
AB  - OBJECTIVE: It has been shown that verbal working and associative memory have
      different developmental trajectories with working memory, taking a linear course
      from early childhood to adolescence, whereas associative memory takes a
      curvilinear course asymptoting at about age 12. This study made a determination
      of whether these trajectories tracked with 2 magnetic resonance spectroscopy
      imaging (MRSI) variables: phosphocreatine level (PCr) and gray matter percentage
      (GM%). METHOD: In a cross-sectional study, 94 children ranging in age from 6-14
      years were administered tests of verbal working and associative memory and
      underwent an MRSI procedure evaluating 6 major brain regions. The study
      considered PCr levels and GM% in the 6 regions. Loess curves were constructed
      plotting the memory tests and MRSI variables across age, and trajectories were
      evaluated. RESULTS: PCr showed a linear increase with age, particularly in the
      left superior temporal lobe with this increase closely tracking improvement in
      working memory but not associative memory scores. GM% did not increase with age
      in any brain region, and there was no tracking with either of the memory tests.
      CONCLUSION: Verbal working memory and verbal associative memory have differing
      age trajectories, with working memory showing close tracking with PCr level,
      mainly in the left superior temporal lobe. No such tracking was found for the
      associative memory tests. GM% curves were flat across regions, showing no
      association with age.

PMID- 24564284
TI  - Hydrogenation-assisted graphene origami and its application in programmable
      molecular mass uptake, storage, and release.
AB  - The malleable nature of atomically thin graphene makes it a potential candidate
      material for nanoscale origami, a promising bottom-up nanomanufacturing approach
      to fabricating nanobuilding blocks of desirable shapes. The success of graphene
      origami hinges upon precise and facile control of graphene morphology, which
      still remains as a significant challenge. Inspired by recent progresses on
      functionalization and patterning of graphene, we demonstrate hydrogenation
      assisted graphene origami (HAGO), a feasible and robust approach to enabling the
      formation of unconventional carbon nanostructures, through systematic molecular
      dynamics simulations. A unique and desirable feature of HAGO-enabled
      nanostructures is the programmable tunability of their morphology via an external
      electric field. In particular, we demonstrate reversible opening and closing of a
      HAGO-enabled graphene nanocage, a mechanism that is crucial to achieve molecular
      mass uptake, storage, and release. HAGO holds promise to enable an array of
      carbon nanostructures of desirable functionalities by design. As an example, we
      demonstrate HAGO-enabled high-density hydrogen storage with a weighted percentage
      exceeding the ultimate goal of US Department of Energy. 

PMID- 24564285
TI  - Solution structures, stabilities, kinetics, and dynamics of DO3A and DO3A
      sulphonamide complexes.
AB  - The Gd(3+)-DO3A-arylsulphonamide (DO3A-SA) complex is a promising pH-sensitive
      MRI agent. The stability constants of the DO3A-SA and DO3A complexes formed with
      Mg(2+), Ca(2+), Mn(2+), Zn(2+), and Cu(2+) ions are similar, whereas the logKLnL
      values of Ln(DO3A-SA) complexes are 2 orders of magnitude higher than those of
      the Ln(DO3A) complexes. The protonation constant (log KMHL) of the sulphonamide
      nitrogen in the Mg(2+), Ca(2+), Mn(2+), Zn(2+), and Cu(2+) complexes is very
      similar to that of the free ligand, whereas the logKLnHL values of the Ln(DO3A
      SA) complexes are lower by about 4 logK units, indicating a strong interaction
      between the Ln(3+) ions and the sulphonamide N atom. The Ln(HDO3A-SA) complexes
      are formed via triprotonated *Ln(H3DO3A-SA) intermediates which rearrange to the
      final complex in an OH(-)-assisted deprotonation process. The transmetalation
      reaction of Gd(HDO3A-SA) with Cu(2+) is very slow (t1/2 = 5.6 * 10(3) h at pH =
      7.4), and it mainly occurs through proton-assisted dissociation of the complex.
      The (1)H and (13)C NMR spectra of the La-, Eu-, Y-, and Lu(DO3A-SA) complexes
      have been assigned using 2D correlation spectroscopy (COSY, EXSY, HSQC). Two sets
      of signals are observed for Eu-, Y-, and Lu(DO3A-SA), showing two coordination
      isomers in solution, that is, square antiprismatic (SAP) and twisted square
      antiprismatic (TSAP) geometries with ratios of 86-14, 93-7, and 94-6%,
      respectively. Line shape analysis of the (13)C NMR spectra of La-, Y- , and
      Lu(DO3A-SA) gives higher rates and lower activation entropy values compared to
      Ln(DOTA) for the arm rotation, which indicates that the Ln(DO3A-SA) complexes are
      less rigid due to the larger flexibility of the ethylene group in the
      sulphonamide pendant arm. The fast isomerization and the lower activation
      parameters of Ln(DO3A-SA) have been confirmed by theoretical calculations in
      vacuo and by using the polarizable continuum model. The solid state X-ray
      structure of Cu(H2DO3A-SA) shows distorted octahedral coordination. The
      coordination sites of Cu(2+) are occupied by two ring N- and two carboxylate O
      atoms in equatorial position. The other two ring N-atoms complete the
      coordination sphere in axial positions. The solid state structure also indicates
      that a carboxylate O atom and the sulphonamide nitrogen are protonated and
      noncoordinated.

PMID- 24564286
TI  - Infection with respiratory syncytial virus influences FasL-mediated apoptosis of
      pulmonary gammadelta T cells in a murine model of allergen sensitization.
AB  - BACKGROUND: It has been reported that adoptive transfer of gammadelta T cells
      increases the cellular infiltration, especially eosinophils, in the lungs of
      allergic mice, suggesting that gammadelta T cells may play a proinflammatory role
      in allergic airway inflammation. Respiratory syncytial virus (RSV) infection can
      decrease the number of Th2-type gammadelta T cells. However, the underlying
      mechanisms remain unknown. METHODS: BALB/c mice were inoculated intranasally with
      RSV before or after sensitization to OVA. The amounts of Th1/Th2 cytokines as
      well as the levels of specific antibodies were determined by ELISA. The apoptotic
      death of pulmonary gammadelta T cells was analyzed by flow cytometry. RESULTS:
      Adoptive transfer of gammadelta T cells increased the production of Th2 cytokines
      in the lungs and allergy-related antibodies in the serum, further confirming that
      gammadelta T cells act as pro-inflammatory cells or a promoter for the
      development of allergic asthma. RSV infection before sensitization to OVA
      enhanced apoptotic death of pulmonary gammadelta T cells. The percentage and
      absolute number of FasL-expressing gammadelta T cells in the lungs of allergic
      mice were elicited significantly by prior RSV infection. Blocking FasL with
      monoclonal antibody diminished apoptotic death of gammadelta T cells, suggesting
      that FasL is important for RSV-induced apoptosis of pulmonary gammadelta T cells.
      CONCLUSIONS: This work provides evidence that RSV infection suppresses the
      subsequent development of OVA-induced allergic responses partly by enhancing FasL
      mediated apoptosis of pulmonary gammadelta T cells.

PMID- 24564287
TI  - Enhancing the versatility and functionality of fast photochromic bridged
      imidazole dimers by flipping imidazole rings.
AB  - The widely tunable optical properties and the visible sensitivity have been
      required for fast photochromic molecules whose coloration-decoloration cycle
      completes in MUs to ms time scale not only for practical applications such as
      full-color holographic displays but also for fundamental researches in
      biochemistry. However, the so far developed [2.2]paracyclophane-bridged imidazole
      dimers, which are one of the best candidates for fast photochromic molecules,
      have their weaknesses for these requirements. Herein, we overcome the issues with
      sustaining fast photochromism and high durability by flipping the two imidazole
      rings (the head-to-tail and tail-to-tail forms). The alteration in the relative
      configuration of the imidazole rings suppresses the broad absorption band
      resulting from the radical-radical interaction. The substitution to the 2
      position of the imidazole ring of the tail-to-tail form gives the drastic changes
      in the steady-state and the transient absorption spectra. The pyrene-substituted
      tail-to-tail form demonstrates that the transient absorption spectrum is featured
      by the inherent spectrum of the imidazolyl radical. This molecular framework is
      easy to functionalize fast photochromic molecules such as sensitizations to the
      red light, chirality, and biological tagging, and therefore it is versatile for
      various fast photochromic applications. 

PMID- 24564288
TI  - The Body Action Coding System I: muscle activations during the perception and
      expression of emotion.
AB  - Body postures provide clear signals about emotional expressions, but so far it is
      not clear what muscle patterns are associated with specific emotions. This study
      lays the groundwork for a Body Action Coding System by investigating what
      combinations of muscles are used for emotional bodily expressions and assessing
      whether these muscles also automatically respond to the perception of emotional
      behavior. Surface electromyography of muscles in the arms (biceps and triceps)
      and shoulders (upper trapezius and deltoids) were measured during both active
      expression and passive viewing of fearful and angry bodily expressions. The
      biceps, deltoids, and triceps are recruited strongly for the expression of anger
      and fear expression predominantly depends on the biceps and the deltoids. During
      passive viewing, all muscles automatically activate during the passive viewing of
      anger. During fear perception, a clear activation can be seen in the trapezius,
      deltoid, and triceps muscles, whereas the biceps shows inhibition. In conclusion,
      this study provides more insight into the perception and expression of emotions
      in the body. 

PMID- 24564289
TI  - Developing an interactive mobile phone self-report system for self-management of
      hypertension. Part 1: patient and professional perspectives.
AB  - Low adherence remains a struggle in hypertension management, despite improvement
      efforts. Presuming that increased patient participation is a possible approach,
      we collaborated with patients and healthcare professionals to design a self
      report system to support self-management. The study aimed to explore and describe
      relevant aspects of hypertension and hypertension treatment, for use in the
      development of an interactive mobile phone self-report system. It further aimed
      to suggest which clinical measures, lifestyle measures, symptoms and side-effects
      of treatment would be meaningful to include in such a system. Five focus group
      interviews were performed with 15 patients and 12 healthcare professionals, and
      data was analysed using thematic analysis. Patients suggested trust, a good
      relationship with caregivers, and well-being as important aspects of hypertension
      self-management. Furthermore, they regarded blood pressure, dizziness, stress,
      headache and tiredness as important outcomes to include. Patients sought to
      understand interconnections between symptoms and variations in blood pressure,
      whilst healthcare professionals doubted patients' ability to do so. Healthcare
      professionals emphasized accessibility, clear and consistent counselling,
      complication prevention and educational efforts. The study presents aspects of
      importance for follow-up to understand the interplay between blood pressure and
      daily life experiences for patients with hypertension.

PMID- 24564290
TI  - Automatic B cell lymphoma detection using flow cytometry data.
AB  - BACKGROUND: Flow cytometry has been widely used for the diagnosis of various
      hematopoietic diseases. Although there have been advances in the number of
      biomarkers that can be analyzed simultaneously and technologies that enable fast
      performance, the diagnostic data are still interpreted by a manual gating
      strategy. The process is labor-intensive, time-consuming, and subject to human
      error. RESULTS: We used 80 sets of flow cytometry data from 44 healthy donors, 21
      patients with chronic lymphocytic leukemia (CLL), and 15 patients with follicular
      lymphoma (FL). Approximately 15% of data from each group were used to build the
      profiles. Our approach was able to successfully identify 36/37 healthy donor
      cases, 18/18 CLL cases, and 12/13 FL cases. CONCLUSIONS: This proof-of-concept
      study demonstrated that an automated diagnosis of CLL and FL can be obtained by
      examining the cell capture rates of a test case using the computational method
      based on the multi-profile detection algorithm. The testing phase of our system
      is efficient and can facilitate diagnosis of B-lymphocyte neoplasms.

PMID- 24564292
TI  - Solvent dependence of the electronic structure of I(-) and I3(-).
AB  - We present synchrotron-based I4d photoelectron spectroscopy experiments of
      solutions from LiI and LiI3 in water, ethanol, and acetonitrile. The
      experimentally determined solvent-induced binding energy shifts (SIBES) for the
      monatomic I(-) anion are compared to predictions from simple Born theory, PCM
      calculations, as well as multiconfigurational quantum chemical spectral
      calculations from geometries obtained through molecular dynamics of solvated
      clusters. We show that the SIBES for I(-) explicitly depend on the details of the
      hydrogen bonding configurations of the solvent to the I(-) and that static
      continuum models such as the Born model cannot capture the trends in the SIBES
      observed both in experiments and in higher-level calculations. To extend the
      discussion to more complex polyatomic anions, we also performed experiments on
      I3(-) and I(-)/I3(-) mixtures in different solvents and the results are analyzed
      in the perspective of SIBES. The experimental SIBES values indicate that the
      solvation effects even for such similar anions as I(-) and I3(-) can be rather
      different in nature.

PMID- 24564291
TI  - MaTSE: the gene expression time-series explorer.
AB  - BACKGROUND: High throughput gene expression time-course experiments provide a
      perspective on biological functioning recognized as having huge value for the
      diagnosis, treatment, and prevention of diseases. There are however significant
      challenges to properly exploiting this data due to its massive scale and
      complexity. In particular, existing techniques are found to be ill suited to
      finding patterns of changing activity over a limited interval of an experiments
      time frame. The Time-Series Explorer (TSE) was developed to overcome this
      limitation by allowing users to explore their data by controlling an animated
      scatter-plot view. MaTSE improves and extends TSE by allowing users to visualize
      data with missing values, cross reference multiple conditions, highlight gene
      groupings, and collaborate by sharing their findings. RESULTS: MaTSE was
      developed using an iterative software development cycle that involved a high
      level of user feedback and evaluation. The resulting software combines a variety
      of visualization and interaction techniques which work together to allow
      biologists to explore their data and reveal temporal patterns of gene activity.
      These include a scatter-plot that can be animated to view different temporal
      intervals of the data, a multiple coordinated view framework to support the cross
      reference of multiple experimental conditions, a novel method for highlighting
      overlapping groups in the scatter-plot, and a pattern browser component that can
      be used with scatter-plot box queries to support cooperative visualization. A
      final evaluation demonstrated the tools effectiveness in allowing users to find
      unexpected temporal patterns and the benefits of functionality such as the
      overlay of gene groupings and the ability to store patterns. CONCLUSIONS: We have
      developed a new exploratory analysis tool, MaTSE, that allows users to find
      unexpected patterns of temporal activity in gene expression time-series data.
      Overall, the study acted well to demonstrate the benefits of an iterative
      software development life cycle and allowed us to investigate some visualization
      problems that are likely to be common in the field of bioinformatics. The
      subjects involved in the final evaluation were positive about the potential of
      MaTSE to help them find unexpected patterns in their data and characterized MaTSE
      as an exploratory tool valuable for hypothesis generation and the creation of new
      biological knowledge.

PMID- 24564294
TI  - Provenance in bioinformatics workflows.
AB  - In this work, we used the PROV-DM model to manage data provenance in workflows of
      genome projects. This provenance model allows the storage of details of one
      workflow execution, e.g., raw and produced data and computational tools, their
      versions and parameters. Using this model, biologists can access details of one
      particular execution of a workflow, compare results produced by different
      executions, and plan new experiments more efficiently. In addition to this, a
      provenance simulator was created, which facilitates the inclusion of provenance
      data of one genome project workflow execution. Finally, we discuss one case
      study, which aims to identify genes involved in specific metabolic pathways of
      Bacillus cereus, as well as to compare this isolate with other phylogenetic
      related bacteria from the Bacillus group. B. cereus is an extremophilic bacteria,
      collected in warm water in the Midwestern Region of Brazil, its DNA samples
      having been sequenced with an NGS machine. 

PMID- 24564293
TI  - Toxic optic neuropathy in the setting of docetaxel chemotherapy: a case report.
AB  - BACKGROUND: To describe the first reported case of toxic optic neuropathy
      secondary to docetaxel (Taxotere(r)) chemotherapy. CASE PRESENTATION: A 53-year
      old female presented with predominantly unilateral visual loss, but extensive
      bilateral visual field defects and bilateral optic nerve head swelling 2 weeks
      after first dose of docetaxel (Taxotere(r)) and trastuzumab (Herceptin(r))
      chemotherapy for a left sided node-positive, HER2 positive breast cancer.
      Extensive investigation ruled out other causes of optic neuropathy. She was
      treated with high dose corticosteroids intravenously for 1 week then a tapering
      oral dose over 8 weeks. Visual field defects gradually resolved and visual acuity
      improved. Docetaxel chemotherapy was discontinued but targeted therapy with
      trastuzumab continued without further complication. CONCLUSION: Docetaxel can
      cause a toxic optic neuropathy possibly due to an ischemic or neurotoxic
      mechanism at the optic nerve head. With cessation of docetaxel therapy and
      treatment with systemic corticosteroids, visual recovery can occur without
      significant residual visual deficit.

PMID- 24564295
TI  - Sol-gel derived transparent zirconium-phenyl siloxane hybrid for robust high
      refractive index LED encapsulant.
AB  - We report a zirconium-phenyl siloxane hybrid material (ZPH) that can be used as a
      robust LED encapsulant. The ZPH encapsulant was fabricated via hydrosilylation
      curing of sol-gel derived multifunctional (vinyl- and hydride-functions) siloxane
      resins containing phenyl-groups and Zr-O-Si heterometallic phase for achieving a
      high refractive index (n ~ 1.58). In thermal aging, the ZPH LED encapsulant
      exhibited superior performances with a high optical transparency (~88% at 450 nm)
      and exhibited high thermal stability (no yellowing at 180  degrees C for 1008 h),
      compared to a commercial LED encapsulant (OE-6630, Dow Corning Corporation). This
      suggests potential for ZPH to be a robust LED encapsulant. 

PMID- 24564296
TI  - Integrating microRNA target predictions for the discovery of gene regulatory
      networks: a semi-supervised ensemble learning approach.
AB  - BACKGROUND: MicroRNAs (miRNAs) are small non-coding RNAs which play a key role in
      the post-transcriptional regulation of many genes. Elucidating miRNA-regulated
      gene networks is crucial for the understanding of mechanisms and functions of
      miRNAs in many biological processes, such as cell proliferation, development,
      differentiation and cell homeostasis, as well as in many types of human tumors.
      To this aim, we have recently presented the biclustering method HOCCLUS2, for the
      discovery of miRNA regulatory networks. Experiments on predicted interactions
      revealed that the statistical and biological consistency of the obtained networks
      is negatively affected by the poor reliability of the output of miRNA target
      prediction algorithms. Recently, some learning approaches have been proposed to
      learn to combine the outputs of distinct prediction algorithms and improve their
      accuracy. However, the application of classical supervised learning algorithms
      presents two challenges: i) the presence of only positive examples in datasets of
      experimentally verified interactions and ii) unbalanced number of labeled and
      unlabeled examples. RESULTS: We present a learning algorithm that learns to
      combine the score returned by several prediction algorithms, by exploiting
      information conveyed by (only positively labeled/) validated and unlabeled
      examples of interactions. To face the two related challenges, we resort to a semi
      supervised ensemble learning setting. Results obtained using miRTarBase as the
      set of labeled (positive) interactions and mirDIP as the set of unlabeled
      interactions show a significant improvement, over competitive approaches, in the
      quality of the predictions. This solution also improves the effectiveness of
      HOCCLUS2 in discovering biologically realistic miRNA:mRNA regulatory networks
      from large-scale prediction data. Using the miR-17-92 gene cluster family as a
      reference system and comparing results with previous experiments, we find a large
      increase in the number of significantly enriched biclusters in pathways,
      consistent with miR-17-92 functions. CONCLUSION: The proposed approach proves to
      be fundamental for the computational discovery of miRNA regulatory networks from
      large-scale predictions. This paves the way to the systematic application of
      HOCCLUS2 for a comprehensive reconstruction of all the possible multiple
      interactions established by miRNAs in regulating the expression of gene networks,
      which would be otherwise impossible to reconstruct by considering only
      experimentally validated interactions.

PMID- 24564297
TI  - Reflections on the immunology of tuberculosis: will we ever unravel the skein?
AB  - Many and large dumps exist in our knowledge about Mycobacterium tuberculosis
      infection and disease in infants and children. We still do not understand why
      some individuals do acquire and others do not acquire the infection in the
      presence of the same risk factors. We do not understand why some individuals
      convert from latent to active tuberculosis and why other individuals convert from
      active to inactive tuberculosis even without treatment. As a matter of fact the
      immune system mounts a bouncing, robust and polyedral defence against
      Mycobacterium tuberculosis, but the bacillus is so much artful and dextrous that
      it has ahead from this immunological fierce accoutrements. Mycobacterium
      tuberculosis survival, multiplication, and transmission are largely favoured by
      the immune mechanisms. The granuloma itself is more bacillus- than host
      protective. These abilities make Mycobacterium tuberculosis one of more
      successful human pathogens, but dumps in our knowledge and the counterproductive
      immunity hinder development of new diagnostics, therapies and vaccines. This
      occurs in front of an infection which engages one third of the world population
      and a disease which kills in a year about 1.5 million individuals worldwide.
      Understanding mechanisms and meaning of immune response in tuberculosis marks out
      the foundations of strategies with a view to prepare effective vaccines and
      reliable diagnostic tools as well as to build up therapeutic weapons. To gain
      these objectives is vital and urgent considering that tuberculosis is a common
      cause of morbidity and is a leading cause of death.

PMID- 24564298
TI  - Estimating the child health equity potential of improved sanitation in Nepal.
AB  - BACKGROUND: Access to improved sanitation plays an important role in child health
      through its impact on diarrheal mortality and malnutrition. Inequities in
      sanitation coverage translate into health inequities across socio-economic
      groups. This paper presents the differential impact on child mortality and
      diarrheal incidence of expanding sanitation coverage across wealth quintiles in
      Nepal. METHODS: We modeled three scale up coverage scenarios at the national
      level and at each of the 5 wealth quintiles for improved sanitation in Nepal in
      the Lives Saved Tool (LiST): equal for all quintiles, realistically pro-poor and
      ambitiously pro-poor. RESULTS: The results show that equal improvement in
      sanitation coverage can save a total of 226 lives (10.7% of expected diarrhea
      deaths), while a realistically pro-poor program can save 451 child lives (20.5%)
      and the ambitiously pro-poor program can save 542 lives (24.6%). CONCLUSIONS: Pro
      poor policies for expanding sanitation coverage have the ability to reduce
      population level health inequalities which can translate into reduced child
      diarrheal mortality.

PMID- 24564299
TI  - Dissemination of an Internet-based treatment for chronic insomnia into primary
      care.
AB  - This study evaluated the effectiveness of two strategies (provider-targeted,
      consumer-targeted) in the dissemination of an insomnia treatment into primary
      care. Results of the study indicated that more patients from the provider
      targeted, than the consumer-targeted, clinic followed up on the referral for
      insomnia treatment, but that overall there was limited uptake. These results did
      not seem to be associated with low levels of provider interest, although
      providers expressed need for more education about the insomnia program.
      Implications of these results are that future research efforts would benefit from
      expanding upon the education of providers in terms of treatment offered, perhaps
      teaching providers how to better motivate their patients for behavior change. 

PMID- 24564300
TI  - Graphene oxide promotes the differentiation of mouse embryonic stem cells to
      dopamine neurons.
AB  - AIM: Nanoparticles are easier to pass through cell membranes, and they are
      considered to be the ideal biocompatible and mechanically stable platforms for
      supporting stem cell growth and differentiation. The aim of this study is to
      determine the effects of carbon nanotubes (CNTs), graphene oxide (GO) and
      graphene (GR) on the dopamine neural differentiation of mouse embryonic stem
      cells (ESCs). MATERIALS & METHODS: GO was prepared according to a modified
      Hummers method. GR was synthesized by reduction of GO via L-ascorbic acid as a
      reductant in an aqueous solution at room temperature. CNTs were fabricated by
      chemical vapor deposition method. ESCs were differentiated by a stromal cell
      derived inducing activity (SDIA) method after 10 days coculture with PA6 cells.
      The dopamine neural differentiation of the ESCs-GFP was examined by
      immunocytochemistry and real-time PCR. RESULTS: We found that only GO could
      effectively promote dopamine neuron differentiation after induction of SDIA and
      further enhance dopamine neuron-related gene expression compared with cells
      treated with no nanoparticle control, and the other two nanoparticles (CNTs and
      GR). CONCLUSION: These findings suggest that GO is a promising nanomaterial-based
      technical platform to effectively enhance dopamine neural differentiation of
      ESCs, which can be potentially applied for cell transplantation therapy.

PMID- 24564301
TI  - Synthesis of dibarrelane, a dibicyclo[2.2.2]octane hydrocarbon.
AB  - The synthesis of a novel hydrocarbon, dibarrelane, has been accomplished in 11
      steps via an intramolecular REDDA reaction of a masked o-benzoquinone, followed
      by Clemmensen reduction and Barton decarboxylation. The twisted structure of the
      tetracyclic dibarrelane skeleton was also clarified via X-ray crystallography.
      Finally, it was proposed that dibarrelane has C2 symmetry rather than C(2v)
      symmetry.

PMID- 24564302
TI  - Controlling graphene ultrafast hot carrier response from metal-like to
      semiconductor-like by electrostatic gating.
AB  - We investigate the ultrafast terahertz response of electrostatically gated
      graphene upon optical excitation. We observe that the photoinduced terahertz
      absorption increases in charge neutral graphene but decreases in highly doped
      graphene. We show that this transition from semiconductor-like to metal-like
      response is unique for zero bandgap materials such as graphene. In charge neutral
      graphene photoexcited hot carriers effectively increase electron and hole
      densities and increase the conductivity. In highly doped graphene, however,
      photoexcitation does not change net conducting carrier concentration. Instead, it
      mainly increases electron scattering rate and reduce the conductivity. 

PMID- 24564303
TI  - Practical aliquoting of flowering plant genomes.
AB  - We pose the problem of dissecting an ancient polyploid genome into its
      constituent subgenomes despite fragmentation and noise caused by genome
      rearrangements and fractionation of multi-copy genes. We formulate this in terms
      of decomposition into "defective" k-partite graphs, distinguished by location
      within the genome. We devise and implement a clustering heuristic for solving
      realistic instances of the problem. An unusual focus of our method is the focus
      on prioritizing gene density or lack of gaps in the assembly of fragments into
      larger regions, rather than maximizing the number of genes. We validate the
      method against the grape genome in which the ancient core eudicot triplication is
      readily detectible and is already well known. We then analyze the tomato genome,
      whose proposed status as a descendant of a more recent Solanum hexaploid is
      controversial, and confirm this proposal. The solution reveals unexpected
      information about the evolution of the tomato. 

PMID- 24564304
TI  - Supervised categorical principal component analysis for genome-wide association
      analyses.
AB  - In order to have a better understanding of unexplained heritability for complex
      diseases in conventional Genome-Wide Association Studies (GWAS), aggregated
      association analyses based on predefined functional regions, such as genes and
      pathways, become popular recently as they enable evaluating joint effect of
      multiple Single-Nucleotide Polymorphisms (SNPs), which helps increase the
      detection power, especially when investigating genetic variants with weak
      individual effects. In this paper, we focus on aggregated analysis methods based
      on the idea of Principal Component Analysis (PCA). The past approaches using PCA
      mostly make some inherent genotype data and/or risk effect model assumptions,
      which may hinder the accurate detection of potential disease SNPs that influence
      disease phenotypes. In this paper, we derive a general Supervised Categorical
      Principal Component Analysis (SCPCA), which explicitly models categorical SNP
      data without imposing any risk effect model assumption. We have evaluated the
      efficacy of SCPCA with the comparison to a traditional Supervised PCA (SPCA) and
      a previously developed Supervised Logistic Principal Component Analysis (SLPCA)
      based on both the simulated genotype data by HAPGEN2 and the genotype data of
      Crohn's Disease (CD) from Wellcome Trust Case Control Consortium (WTCCC). Our
      preliminary results have demonstrated the superiority of SCPCA over both SPCA and
      SLPCA due to its modeling explicitly designed for categorical SNP data as well as
      its flexibility on the risk effect model assumption. 

PMID- 24564308
TI  - Comparison of the cardiorespiratory effects of a combination of ketamine and
      propofol, propofol alone, or a combination of ketamine and diazepam before and
      after induction of anesthesia in dogs sedated with acepromazine and oxymorphone.
AB  - OBJECTIVE: To evaluate the cardiorespiratory effects of IV administration of
      propofol (4 mg/kg), ketamine hydrochloride and propofol (2 mg/kg each; K-P), or
      ketamine hydrochloride (5 mg/kg) and diazepam (0.2 mg/kg; K-D) before and after
      induction of anesthesia (IoA) in dogs sedated with acepromazine maleate and
      oxymorphone hydrochloride. ANIMALS: 10 healthy adult Beagles. PROCEDURES: Each
      dog was randomly allocated to receive 2 of 3 treatments (1-week interval). For
      instrumentation prior to each treatment, each dog was anesthetized with
      isoflurane. After full recovery, acepromazine (0.02 mg/kg) and oxymorphone (0.05
      mg/kg) were administered IV. Fifteen minutes later (before IoA), each dog
      received treatment IV with propofol, K-P, or K-D. Cardiorespiratory and arterial
      blood gas variables were assessed before, immediately after, and 5 minutes after
      IoA. RESULTS: Compared with findings before IoA, dogs receiving the K-P or K-D
      treatment had increased cardiac output, oxygen delivery, and heart rate 5 minutes
      after IoA; K-P administration did not change mean arterial blood pressure or
      stroke volume and decreased systemic vascular resistance. Propofol decreased mean
      arterial blood pressure and systemic vascular resistance immediately after IoA
      but did not change heart rate, cardiac output, or oxygen delivery. All treatments
      caused some degree of apnea, hypoventilation, and hypoxemia (Pao2 < 80 mm Hg).
      CONCLUSIONS AND CLINICAL RELEVANCE: In dogs, K-P treatment maintained mean
      arterial blood pressure better than propofol alone and increased heart rate,
      cardiac output, or oxygen delivery, as did the K-D treatment. Supplemental 100%
      oxygen should be provided during IoA with all 3 treatments.

PMID- 24564307
TI  - Effects of acetylcholinesterase inhibition on quality of recovery from isoflurane
      induced anesthesia in horses.
AB  - OBJECTIVE: To compare effects of 2 acetylcholinesterase inhibitors on recovery
      quality of horses anesthetized with isoflurane. ANIMALS: 6 horses in phase 1, 7
      horses in phase 2A, and 14 horses in phase 2B. PROCEDURES: The study comprised 3
      phases (2 randomized, blinded crossover phases in horses undergoing orthopedic
      procedures and 1 prospective dose-determining phase). In phase 1, horses were
      anesthetized with isoflurane and received neostigmine or saline (0.9% NaCl)
      solution prior to anesthetic recovery. Phase 2A was a physostigmine dose
      determining phase. In phase 2B, horses were anesthetized with isoflurane and
      received neostigmine or physostigmine prior to recovery. Objective recovery
      events were recorded and subjective visual analogue scale scores of recovery
      quality were assigned from video recordings. RESULTS: Recovery measures in phase
      1 were not different between horses receiving neostigmine or saline solution. In
      phase 2A, 0.04 mg of physostigmine/kg was the highest cumulative dose that did
      not cause clinically relevant adverse behavioral or gastrointestinal effects.
      Horses receiving physostigmine had higher mean +/- SD visual analogue scale
      recovery scores (70.8 +/- 13.3 mm) than did horses receiving neostigmine (62.4 +/
      12.8 mm) in phase 2B, with fewer attempts until sternal and standing recovery.
      Incidence of colic behavior did not differ among groups. CONCLUSIONS AND CLINICAL
      RELEVANCE: Inhibition with physostigmine improved anesthetic recovery quality in
      horses anesthetized with isoflurane, compared with recovery quality for horses
      receiving neostigmine. Inhibition of central muscarinic receptors by inhalation
      anesthetics may underlie emergence delirium in horses recovering from anesthesia.

PMID- 24564309
TI  - In vivo assessment of a multicomponent and nanostructural polymeric matrix as a
      delivery system for antimicrobials and bone morphogenetic protein-2 in a
      unicortical tibial defect in goats.
AB  - OBJECTIVE: To determine the response of cortical bone to a multicomponent and
      nanostructural polymeric matrix as a drug delivery system for enhancing bone
      healing. ANIMALS: 20 healthy adult crossbred goats. PROCEDURES: A 3.5-mm-diameter
      unicortical defect was created in each tibia (day 0), and goats (4 goats/group)
      were treated as follows: not treated (control group), grafted with the matrix,
      grafted with antimicrobial (tigecycline and tobramycin)-impregnated matrix,
      grafted with recombinant human bone morphogenetic protein type 2 (rhBMP-2)
      impregnated matrix, or grafted with antimicrobial- and rhBMP-2-impregnated
      matrix. Elution kinetics of antimicrobials was monitored through plasma
      concentrations. Bone response was assessed with radiographic scoring (days 1 and
      30) and dual-energy x-ray absorptiometry (days 1, 14, and 30). Goats were
      euthanized on day 30, and histomorphologic analysis was performed. Categorical
      variables were analyzed with a generalized linear model, and continuous variables
      were analyzed with an ANOVA. RESULTS: Plasma antimicrobial concentrations
      indicated continued release throughout the study. Radiography and dual-energy x
      ray absorptiometry did not reveal significant differences among treatments on day
      30. Periosteal reactions were significantly greater surrounding bone defects
      grafted with rhBMP-2-impregnated matrix than those not treated or grafted with
      matrix or with antimicrobial-impregnated matrix; periosteal reactions were
      similar in bone defects grafted with rhBMP-2-impregnated matrix and antimicrobial
      and rhBMP-2-impregnated matrix. CONCLUSIONS AND CLINICAL RELEVANCE: The matrix
      served as an antimicrobial delivery system and stimulated bone proliferation when
      rhBMP-2 was present. Antimicrobial and rhBMP-2 can be used concurrently, but the
      presence of antimicrobials may affect the performance of rhBMP-2.

PMID- 24564310
TI  - Evaluation of the accuracy of neurologic data, survey radiographic results, or
      both for localization of the site of thoracolumbar intervertebral disk herniation
      in dogs.
AB  - OBJECTIVE: To determine the accuracy of neurologic data, survey radiographic
      results, or both for localization of the site of thoracolumbar intervertebral
      disk herniation in dogs. SAMPLE: 338 dogs with surgically confirmed
      intervertebral disk herniation from disk spaces T10-11 to L6-7. PROCEDURES:
      Medical records and archived survey radiographs were reviewed for each case. Data
      were analyzed with multivariable logistic regression models. Three models were
      fit to develop subsets of the data consisting of survey radiographic data,
      neurologic examination data, and a combination of survey radiographic and
      neurologic examination data. The resulting models were validated by evaluating
      predictive performance against a validation subset of the data. RESULTS: Models
      incorporating survey radiographic data and a combination of survey radiographic
      and neurologic data had similar predictive ability and performed better than the
      model based solely on neurologic data but resulted in substantial errors in
      predictions. CONCLUSIONS AND CLINICAL RELEVANCE: A combination of neurologic
      examination data as recorded in the medical records and radiographic data did not
      enhance predictive performance of multivariable logistic regression models over
      models limited to radiographic data. Neurologic and radiographic findings should
      not be used to completely exclude areas in an abnormal spinal cord region from
      further evaluation with advanced imaging.

PMID- 24564311
TI  - Stochastic model of porcine reproductive and respiratory syndrome virus control
      strategies on a swine farm in the United States.
AB  - OBJECTIVE: To use mathematical modeling to assess the effectiveness of control
      strategies for porcine reproductive and respiratory syndrome (PRRS) virus on a
      swine farm. SAMPLE: A hypothetical small, medium, or large farrow-to-weaning
      swine farm in the Midwestern United States. PROCEDURES: Stochastic models were
      formulated to simulate an outbreak of PRRS on a farm. Control strategies assessed
      in those models included none (baseline) and various combinations of mass
      immunization, herd closure, and gilt acclimatization. Nine different models
      resulting from the combination of low, moderate, or high PRRS virus virulence and
      small, medium, or large herd size were simulated. A stabilized status, the
      outcome of interest, was defined as the absence of positive PCR assay results for
      PRRS virus in 3-week-old piglets. For each scenario, the percentage of
      simulations with a stabilized status was used as a proxy for the probability of
      disease control. RESULTS: Increasing PRRS virus virulence and herd size were
      negatively associated with the probability of achieving a stabilized status.
      Repeated mass immunization with herd closure or gilt acclimitization was a better
      alternative than was single mass immunization for disease control within a farm.
      CONCLUSIONS AND CLINICAL RELEVANCE: Repeated mass immunization with a PRRS
      modified-live virus vaccine with herd closure or gilt acclimitization was the
      scenario most likely to achieve a stabilized status. Estimation of the cost of
      various PRRS control strategies is necessary.

PMID- 24564312
TI  - Detection of misfolded prion protein in retina samples of sheep and cattle by use
      of a commercially available enzyme immunoassay.
AB  - OBJECTIVE: To determine the usefulness of retina samples for detection of disease
      associated prion protein by use of a commercially available enzyme immunoassay
      (EIA) intended for rapid identification of sheep and cattle with transmissible
      spongiform encephalopathies (TSEs). SAMPLES: Retina, brainstem at the level of
      the obex, and retropharyngeal lymph node samples obtained from 15 TSE-inoculated
      sheep (scrapie [n = 13] or transmissible mink encephalopathy passaged through a
      bovid [2]); retina and brainstem samples obtained from 11 TSE-inoculated cattle
      (transmissible mink encephalopathy passaged through a bovid [7] or classical BSE
      [4]); and negative control tissue samples obtained from 2 sheep and 2 cattle that
      were not inoculated with TSEs. PROCEDURES: Tissue samples were homogenized and
      analyzed for detection of abnormally folded disease-associated prion protein with
      a commercially available EIA and 2 confirmatory assays (western blot analysis or
      immunohistochemical analysis). RESULTS: Retina sample EIA results were in
      agreement with results of brainstem sample EIA or confirmatory assay results for
      negative control animals and TSE-inoculated animals with clinical signs of
      disease. However, TSE-inoculated animals with positive confirmatory assay results
      that did not have clinical signs of disease had negative retina sample EIA
      results. Retina sample EIA results were in agreement with brainstem sample
      immunohistochemical results for 4 TSE-inoculated sheep with negative
      retropharyngeal lymph node EIA results. CONCLUSIONS AND CLINICAL RELEVANCE:
      Results of this study suggested that retina samples may be useful for rapid EIA
      screening of animals with neurologic signs to detect TSEs.

PMID- 24564313
TI  - Antiviral efficacy of nine nucleoside reverse transcriptase inhibitors against
      feline immunodeficiency virus in feline peripheral blood mononuclear cells.
AB  - OBJECTIVE: To compare cytotoxic effects and antiviral efficacy of 9 nucleoside
      reverse transcriptase inhibitors (NRTIs) against FIV in feline peripheral blood
      mononuclear cells. SAMPLE: Peripheral blood mononuclear cells obtained from 3
      specific pathogen-free cats. PROCEDURES: 3 of the 9 NRTIs had not been previously
      assessed in feline cell lines. Cytotoxic effects were determined by colorimetric
      quantification of a formazan product resulting from bioreduction of a tetrazolium
      reagent by viable peripheral blood mononuclear cells; uninfected cells from 1 cat
      were used in these assays. Cells from all 3 cats were infected with a pathogenic
      clone of FIV, and in vitro antiviral efficacy of each NRTI was assessed with an
      FIV p24 antigen capture ELISA. RESULTS: Cytotoxic effects in feline peripheral
      blood mononuclear cells were observed only at concentrations > 10 MUM for all 9
      NRTIs. Comparison of the cytotoxic effect at the highest concentration
      investigated (500 MUM) revealed that didanosine and amdoxovir were significantly
      less toxic than abacavir. All drugs induced a dose-dependent reduction of FIV
      replication. At the highest concentration investigated (10 MUM), there was no
      significant difference in antiviral efficacy among the test compounds.
      CONCLUSIONS AND CLINICAL RELEVANCE: The evaluated NRTIs had low cytotoxicity
      against feline peripheral blood mononuclear cells and appeared to be safe options
      for further in vivo evaluation for the treatment of FIV-infected cats. There was
      no evidence suggesting that the newly evaluated compounds would be superior to
      the existing NRTIs for reducing FIV burden of infected cats.

PMID- 24564314
TI  - Effects of intrabursal administration of botulinum toxin type B on lameness in
      horses with degenerative injury to the podotrochlear apparatus.
AB  - OBJECTIVE: To determine the safety and short-term efficacy of intrabursal
      administration of botulinum toxin type B (BTXB) to alleviate lameness in horses
      with degenerative injury to the podotrochlear apparatus (PA). ANIMALS: 10 Quarter
      Horses with degenerative injury to the PA. PROCEDURES: Degenerative injury to the
      PA was confirmed with diagnostic analgesia and imaging. Then, BTXB (3.8 to 4.5
      U/kg) was injected into the podotrochlear (navicular) bursa of each horse. Three
      horses were used in a safety evaluation. Subsequently, video recordings of
      lameness evaluations were obtained for 7 client-owned horses 5 days before
      (baseline) and 7 and 14 days after BTXB treatment and used to determine the
      effect of BTXB injection on lameness; 1 horse was removed from the study 8 days
      after BTXB treatment. Three investigators who were unaware of the treated
      forelimbs or time points separately reviewed the recordings and graded the
      lameness of both forelimbs of the horses. RESULTS: Improvement in lameness of the
      treated forelimbs was detected at 1 or both time points after BTXB administration
      in all horses. However, all horses had some degree of lameness at the end of the
      study. Two horses developed transient increases in lameness 48 to 72 hours after
      treatment; lameness resolved uneventfully. CONCLUSIONS AND CLINICAL RELEVANCE:
      Intrabursal injection of BTXB temporarily alleviated chronic lameness in horses
      with degenerative injury to the PA, without causing serious short-term adverse
      effects. Further investigation into the potential use of BTXB in horses affected
      by degenerative injury to the PA is warranted.

PMID- 24564315
TI  - Pharmacokinetics of ceftiofur crystalline-free acid following subcutaneous
      administration of a single dose to sheep.
AB  - OBJECTIVE: To determine the pharmacokinetics of ceftiofur crystalline-free acid
      (CCFA) following SC administration of a single dose to sheep. ANIMALS: 9 healthy
      adult female Suffolk-crossbred sheep. PROCEDURES: Each sheep was administered 6.6
      mg of CCFA/kg, SC, in the cervical region once. Serial blood samples were
      collected at predetermined intervals for 14 days. Serum concentration of
      ceftiofur free-acid equivalents (CFAE) was determined by high-performance liquid
      chromatography. Pharmacokinetic parameters were determined by compartmental and
      noncompartmental methods. RESULTS: Pharmacokinetics for CCFA following SC
      administration in sheep was best described with a 1-compartment model. Mean +/-
      SD area under the concentration-time curve from time 0 to infinity, peak serum
      concentration, and time to peak serum concentration were 206.6 +/- 24.8 MU*h/mL,
      2.4 +/- 0.5 MUg/mL, and 23.1 +/- 10.1 h, respectively. Serum CFAE concentrations
      >= 1 MUg/mL (the target serum CFAE concentration for treatment of disease caused
      by Mannheimia haemolytica and Pasteurella multocida) were maintained for 2.6 to
      4.9 days. No significant adverse reactions to CCFA administration were observed.
      CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that adequate therapeutic
      serum concentrations of CFAE for treatment of disease caused by M haemolytica and
      P multocida were achieved in sheep following SC administration of a single dose
      (6.6 mg/kg) of CCFA. Thus, CCFA might be useful for the treatment of common
      respiratory tract pathogens in sheep.

PMID- 24564316
TI  - Effects of weather variables on thermoregulation of calves during periods of
      extreme heat.
AB  - OBJECTIVE: To determine effects of ambient temperature, relative humidity, wind
      speed, relative barometric pressure, and temperature-humidity index (THI) on
      nasal submucosal and rectal temperatures in cattle during extreme summer
      conditions. ANIMALS: 20 black crossbred beef heifers (mean body weight, 217.8
      kg). PROCEDURES: Nasal submucosal and rectal temperatures were monitored every 2
      hours for 24 hours on 3 nonconsecutive days when ambient temperature was
      forecasted to exceed 32.2 degrees C. Ambient temperature, relative humidity, wind
      speed, and relative barometric pressure were continuously monitored at a remote
      weather station located at the research facility. The THI was calculated and used
      in the livestock weather safety index (LWSI). Relationships between nasal
      submucosal or rectal temperature and weather variables were evaluated. RESULTS:
      Nasal submucosal and rectal temperatures were related to all weather variables
      monitored. A positive relationship was determined for ambient temperature and THI
      with both nasal submucosal and rectal temperatures. A negative relationship was
      evident for nasal submucosal and rectal temperature with relative humidity, wind
      speed, and relative barometric pressure. Nasal submucosal and rectal temperatures
      increased with increasing severity of LWSI category. CONCLUSIONS AND CLINICAL
      RELEVANCE: Effects of environmental conditions on thermoregulation in calves
      exposed to extreme heat were detected. The positive relationship between nasal
      submucosal temperature and ambient temperature and THI raised concerns about the
      efficacy of intranasal administration of temperature-sensitive modified-live
      virus vaccines during periods of extreme heat. Environmental conditions must be
      considered when rectal temperature is used as a diagnostic tool for identifying
      morbid cattle.

PMID- 24564317
TI  - Effect of body position on intra-abdominal pressures and abdominal perfusion
      pressures measured at three sites in horses anesthetized with short-term total
      intravenous anesthesia.
AB  - OBJECTIVE: To assess effects of body position on direct measurements of intra
      abdominal pressure (IAP) and abdominal perfusion pressure (APP) in horses
      anesthetized with total intravenous anesthesia (TIVA). ANIMALS: 9 healthy adult
      horses. PROCEDURES: Instrumentation in unsedated standing horses involved
      insertion of an arterial catheter for blood pressure measurements and 3
      intraperitoneal cannulas (left flank, right flank, and ventral abdomen) for IAP
      measurements. Baseline values were measured for heart rate, respiratory rate,
      systolic arterial blood pressure, mean arterial blood pressure (MAP), diastolic
      arterial blood pressure, and IAP. Horses were medicated with xylazine, and
      pressures were measured again. Anesthesia was induced with ketamine-diazepam and
      maintained with a ketamine-guaifenesin infusion. Horses were positioned twice
      into left lateral recumbency, right lateral recumbency, or dorsal recumbency.
      Hemodynamic pressures and accessible abdominal pressures were measured for each
      recumbency position. The APP was calculated as MAP - IAP. Differences in IAP,
      MAP, APP and sedation (standing horses) or body position (anesthetized horses)
      were compared by means of repeated-measures ANOVA or paired t tests. RESULTS:
      Baseline hemodynamic and IAPs were not different after xylazine administration.
      Ventral abdomen IAP and MAP were lower for horses in dorsal recumbency than in
      right or left lateral recumbency. Ventral abdomen APP remained unchanged. For
      lateral recumbencies, flank IAP was lower and APP was higher than pressure
      measurements at the same sites during dorsal recumbency. CONCLUSIONS AND CLINICAL
      RELEVANCE: Body position affected IAP and APP in healthy anesthetized horses.
      These effects should be considered when developing IAP acquisition methods for
      use in horses with abdominal disease.

PMID- 24564318
TI  - In vitro effects of the glycoprotein IIb/IIIa receptor antagonists abciximab and
      eptifibatide on platelet aggregation in healthy cats.
AB  - OBJECTIVE: To determine effects of the glycoprotein IIb/IIIa receptor antagonists
      abciximab and eptifibatide on in vitro inhibition of cat platelets. SAMPLE:
      Venous blood samples from 10 healthy cats. PROCEDURES: Blood samples were
      anticoagulated with hirudin. Aliquots of whole blood from each cat were allocated
      to 5 treatments (baseline, 50 MUg of abciximab/mL, abciximab volumetric control
      treatment, 4 MUM eptifibatide, and eptifibatide volumetric control treatment).
      Impedance platelet aggregometry was performed with 6.5 MUM ADP or 32 MUM thrombin
      receptor activator peptide (TRAP). Magnitude of platelet aggregation was
      determined by measuring the area under the curve 15 minutes after addition of ADP
      or TRAP. RESULTS: Eptifibatide caused a significant reduction in platelet
      aggregation, compared with baseline values, for aggregometry with both ADP
      (median, 50.0; range, 8 to 122 [baseline median, 306.0; baseline range, 130 to
      664]) and TRAP (median, 75.5; range, 3 to 148 [baseline median, 219.0; baseline
      range, 97 to 578]). There was no significant difference in platelet aggregation
      with abciximab, the abciximab volumetric control treatment, or the eptifibatide
      volumetric control treatment for aggregometry with ADP or TRAP. CONCLUSIONS AND
      CLINICAL RELEVANCE: Eptifibatide caused a significant reduction in platelet
      aggregation in vitro, but there was no identifiable antiplatelet effect for
      abciximab. Eptifibatide and abciximab have different binding and inhibitory
      actions; therefore, it can be hypothesized that abciximab would be ineffective in
      cats because of a lack of receptor binding, reduced binding kinetics, or lack of
      downstream signaling. Eptifibatide may be useful in identifying hyperreactive
      platelets in cats in an in vitro platelet inhibitory assay.

PMID- 24564319
TI  - Microwell array guided assembly of lipoplex nanoparticles containing siRNA.
AB  - Nucleic acid based therapeutics has been widely explored to treat genetic and
      acquired diseases. However, the clinical translation of nucleic acid based
      therapies has been challenged by low delivery efficiency, off-target effects,
      poor cellular uptake, and limited serum stability. Lipopoplex nanoparticles, as
      one of the major nanocarrier systems, have shown great potential in overcoming
      these challenges. Current techniques for lipoplex nanoparticle preparation rely
      on self-assembly at macroscale, which suffers from limited control over particle
      structure and composition due to local fluctuations in the concentration of the
      constituent materials. We have developed a discontinuous dewetting/imprinting
      method that guided the assembly of lipoplex nanoparticles containing siRNA in a
      microwell array, which achieved much better control on particle size and
      composition. The lipoplex nanoparticles prepared by the discontinuous
      dewetting/imprinting method showed unilamellar core-shell-like structure in
      contrast to the multilamellar onion-like structure generally observed in lipoplex
      nanoparticles prepared by the conventional bulk mixing method. 

PMID- 24564320
TI  - A resettable and reprogrammable DNA-based security system to identify multiple
      users with hierarchy.
AB  - Molecular-level security devices have raised ever-increasing interest in recent
      years to protect data and information from illegal invasion. Prior molecular
      keypad locks have an output signal dependent upon not only the appropriate
      combination but also the exact sequence of inputs, but it cannot be reset or
      reprogrammed. Here, a DNA-based security system with reset and never-reported
      reprogram function is successfully developed in proof-of-principle, with which
      one can change the password in case that the system is cracked. The previous
      password becomes invalid in the reprogrammed security system. Interestingly, more
      than one password is designed to permit multiple users to access. By harnessing
      the intrinsic merit of the different passwords, the system can distinguish
      different user who is endowed with prior authority. The intelligent device is
      addressed on solid support and facilitates electronic processes, avoiding
      chemical accumulation in the system by simple removal of the electrode from the
      input solution and indicating a main avenue for its further development. 

PMID- 24564321
TI  - Hsp90 inhibitors, part 1: definition of 3-D QSAutogrid/R models as a tool for
      virtual screening.
AB  - The multichaperone heat shock protein (Hsp) 90 complex mediates the maturation
      and stability of a variety of oncogenic signaling proteins. For this reason,
      Hsp90 has emerged as a promising target for anticancer drug development. Herein,
      we describe a complete computational procedure for building several 3-D QSAR
      models used as a ligand-based (LB) component of a comprehensive ligand-based (LB)
      and structure-based (SB) virtual screening (VS) protocol to identify novel
      molecular scaffolds of Hsp90 inhibitors. By the application of the 3-D
      QSAutogrid/R method, eight SB PLS 3-D QSAR models were generated, leading to a
      final multiprobe (MP) 3-D QSAR pharmacophoric model capable of recognizing the
      most significant chemical features for Hsp90 inhibition. Both the monoprobe and
      multiprobe models were optimized, cross-validated, and tested against an external
      test set. The obtained statistical results confirmed the models as robust and
      predictive to be used in a subsequent VS. 

PMID- 24564322
TI  - Blunted diurnal cortisol pattern is associated with frailty: a cross-sectional
      study of 745 participants aged 65 to 90 years.
AB  - BACKGROUND: The role of neuroendocrine alterations in the etiology of frailty
      syndrome is still poorly understood. Hypothalamic-pituitary-adrenal axis
      dysregulation is a plausible candidate pathway contributing to frailty. Thus, we
      sought to examine the associations of diurnal cortisol secretion with frailty in
      older adults. METHODS: A cross-sectional analysis was conducted among 745 study
      participants (age 65-90 years, mean age 75.1 years) of the population-based KORA
      Age study. Associations between salivary cortisol measures at awakening (morning
      1 [M1]), 30 minutes after awakening (M2), and evening (E) and frailty criteria
      were determined. RESULTS: Lower cortisol levels in the first morning sample (M1)
      (P = .18) and M2 (P = .14) and increased E levels (P = .004) were observed in
      prefrail (35.17%, n = 262) and frail (3.36%, n = 25) individuals, in a dose
      response manner. Frailty was strongly associated with smaller ratios of morning
      to evening levels; M1 to E ratio (P = .02) and M2 to E ratio (P = .003). Higher
      evening cortisol levels were associated with a 24% increased risk of a prefrail
      state (odds ratio, 1.22; 95% confidence interval, 1.03-1.44). A smaller morning
      to evening ratio was associated with an increased risk of low grip strength
      (1.42, 1.09-1.86) and gait speed (1.31, 1.02-1.68). CONCLUSION: Frailty status is
      associated with blunted cortisol reactivity as demonstrated by lower morning and
      higher evening salivary cortisol levels.

PMID- 24564323
TI  - Thyroid function within the normal range and the risk of depression: a population
      based cohort study.
AB  - CONTEXT: Overt hypo- and hyperthyroidism are associated with an increased risk of
      depression. Little is known about the effects of variation in thyroid function
      within the normal range on the risk of depression. OBJECTIVE: The objective of
      the study was to examine the association between normal-range thyroid function
      and the risk of depression. DESIGN, SETTING, AND PARTICIPANTS: This was a cohort
      study in 1503 Dutch men and women, aged 70.6 (7.3) (mean [SD]) years. At
      baseline, serum TSH, thyroperoxidase antibody levels, and depressive symptoms
      [Center for Epidemiologic Studies Depression Scale (CES-D)] were assessed. A CES
      D of 16 or greater is indicative of a depressive disorder. During follow-up (mean
      8.0 y), participants were continuously monitored for the occurrence of incident
      depressive syndromes (n = 156). RESULTS: Cross-sectionally, persons in the lowest
      TSH tertile (0.3-1.0 mU/L) had more depressive symptoms [CES-D score (mean): 7.95
      vs 6.63, P = .014] as well as an increased risk of a CES-D of 16 or greater
      [10.7% vs 5.0%, odds ratio (95% confidence interval) 2.22 (1.18-4.17)], compared
      with persons in the highest normal range TSH tertile (1.6-4.0 mU/L). In the
      prospective analyses, persons in the lowest TSH tertile who were depression free
      at baseline had a higher risk of incident depressive syndromes [12.3% vs 7.6%,
      odds ratio (95% confidence interval) 1.85 (1.10-3.11)]. Thyroid autoimmunity
      (thyroperoxidase antibody positivity) was not associated with CES-D scores or
      incident depressive syndromes. CONCLUSIONS: Elderly persons with low-normal TSH
      levels have more concurrent depressive symptoms as well as a substantially
      increased risk of developing a depressive syndrome in the subsequent years. This
      study identifies low-normal TSH as an important risk factor for depression in the
      elderly.

PMID- 24564325
TI  - Energy expenditure during everyday activities--a study comparing people with
      varying mobility limitations due to multiple sclerosis and healthy controls.
AB  - PURPOSE: To investigate energy expenditure of people with multiple sclerosis (MS)
      during everyday activities. METHODS: Fifteen healthy controls, 19 people with MS
      who used at most a stick to walk outdoors (MS-A), and 11 people with MS who used
      bilateral support for gait (MS-B) completed scripted everyday activities. A
      portable indirect calorimetry unit calculated energy expenditure. Steps were
      counted from video. RESULTS: There was no significant difference in kcal between
      the three groups (ANOVA: F(2, 42) = 2.877, p = 0.067). There was a significant
      difference in steps: F(2, 42) = 17.93, p < 0.001. (Controls-MS-A 470.5, 95% CI
      85.2, 855.7, Control-MS-B 1091.3, 95% CI 648.5, 1534.1, MS-A-MS-B 620.8, 95% CI
      198.2, 1043.4.) Energy cost of movement was estimated by dividing kcal by steps.
      The Kruskal-Wallis analysis found significant difference for total (x(2 )=
      11.726, df2, p = 0.003), Walking (x(2 )= 9.01, p = 0.011), Stairs (x(2 )= 16.436,
      2, p < 0.001). Post-hoc analysis revealed significant differences between MS-B
      group and control and MS-A groups. CONCLUSIONS: People with MS do not use more
      energy than healthy controls during everyday activities at a self-selected pace.
      People with MS take significantly fewer steps during activities of daily
      living's. People who use bilateral support for gait have greater energy cost per
      step for walking and stairs activities. Implications for Rehabilitation This
      study found that the energy cost of movement is greater for people with MS with
      significant disability. Energy expenditure is an important consideration when
      prescribing physical activity and structured exercise for people with disability.
      It may be more appropriate to have energy, rather than movement, targets when
      prescribing physical activity for this population.

PMID- 24564324
TI  - A fast and selective near-infrared fluorescent sensor for multicolor imaging of
      biological nitroxyl (HNO).
AB  - The first near-infrared fluorescent turn-on sensor for the detection of nitroxyl
      (HNO), the one-electron reduced form of nitric oxide (NO), is reported. The new
      copper-based probe, CuDHX1, contains a dihydroxanthene (DHX) fluorophore and a
      cyclam derivative as a Cu(II) binding site. Upon reaction with HNO, CuDHX1
      displays a five-fold fluorescence turn-on in cuvettes and is selective for HNO
      over thiols and reactive nitrogen and oxygen species. CuDHX1 can detect
      exogenously applied HNO in live mammalian cells and in conjunction with the zinc
      specific, green-fluorescent sensor ZP1 can perform multicolor/multianalyte
      microscopic imaging. These studies reveal that HNO treatment elicits an increase
      in the concentration of intracellular mobile zinc. 

PMID- 24564326
TI  - International classification of functioning, disability and health categories for
      spinal cord injury nursing in China.
AB  - PURPOSE: To explore a set of International Classification of Functioning,
      Disability and Health (ICF) categories that cover the spinal cord injury (SCI)
      nursing practice in China through a national expert survey. METHODS: An internet
      based email survey was used. An original set of ICF categories specifically for
      SCI nursing has been developed from the preliminary studies based on an
      international perspective. For cultural adaptation in China, a national expert
      survey was conducted with Chinese experts on SCI nursing to identify the ICF
      categories that were specifically for SCI nursing in China. The ICF categories
      which received more than 80% support from the experts would be reported. RESULTS:
      Twenty-nine Chinese experts on SCI nursing participated. There were 81 ICF
      categories which received more than 80% agreement among the experts, including 33
      Body Functions categories, eight Body Structures, 24 Activities and
      Participation, six Environmental Factors and 10 Personal Factors items.
      CONCLUSIONS: A set of ICF categories that cover the SCI nursing practice in China
      was identified. It reflects the main issues that Chinese nurses focus on in
      caring SCI patients. These categories can facilitate Chinese nurses to use the
      ICF in multidisciplinary teamwork and improve the participation of nurses in the
      team. Implications for Rehabilitation In China, nurses lack of an effective model
      or tool to communicate with the other health professionals in the rehabilitation
      team for spinal cord injury (SCI) patients. International Classification of
      Functioning, Disability and Health (ICF) is a tool for multidisciplinary use,
      which can promote the communication and collaboration in the healthcare team by
      establishing a common language across different disciplines and sectors. This set
      of ICF categories developed from this study can serve as a roadmap for important
      items for use in clinical practice of Chinese SCI nursing.

PMID- 24564327
TI  - A narrative analysis of a speech pathologist's work with Indigenous Australians
      with acquired communication disorders.
AB  - PURPOSE: To explore in detail the narrative of a speech pathologist (SP) working
      with Indigenous Australian clients with acquired communication disorders
      following stroke or brain injury. There is some evidence that Indigenous clients
      do not find speech pathology rehabilitation to be culturally appropriate but,
      currently, there is very little published on the nature of this service or the
      experiences of SPs who provide this rehabilitation. METHODS: This research uses
      both thematic and structural narrative analysis of data from a semi-structured,
      in-depth interview with a SP to examine the adaptations that she made to address
      the needs of her adult neurological caseload of (mainly) Indigenous Australians
      from both urban and remote regions. RESULTS: The thematic analysis resulted in a
      core theme of flexibility and four other sub-themes: awareness of cultural
      context, client focus/person-centredness, being practical and working ethically.
      The structural narrative analysis allowed insight into the nature of clinical
      reasoning in a context lacking predictability and where previous clinical
      certainties required adaptation. CONCLUSIONS: Individual, detailed narratives are
      useful in exposing the challenges and clinical reasoning behind culturally
      sensitive practice. Implications for Rehabilitation Speech pathologists (SPs) can
      learn from hearing the clinical stories of colleagues with experience of
      providing rehabilitation in culturally diverse contexts, as well as from ongoing
      training in culturally competent and safe practices. Such stories help bridge
      understanding from the general to the particular. SPs working with Indigenous
      Australians with acquired communication disorders post-stroke and brain injury
      may find it helpful to consider how the themes, drawn from an interview with the
      clinician in this study - flexibility, awareness of cultural context, person
      centredness, being practical and working ethically - might apply to their
      practice. Narratives may be helpful in staff training and form an important part
      of the SP evidence base.

PMID- 24564328
TI  - "Strong and steady": a community-based strength and balance exercise group for
      children with cerebral palsy.
AB  - PURPOSE: This study investigated the effect of an eight-week community-based
      strength and balance exercise group for children with cerebral palsy (CP).
      METHOD: Ten children with CP participated in the study (8-15 years; six male;
      GMFCS I = 6, II = 4; five diplegia; five hemiplegia). Muscle strength was
      assessed using dynamometry and functional strength tests (seated throw, distance
      jump, vertical jump). Balance was assessed using the Bruninks-Oseretsky Test of
      Motor Proficiency, the Movement Assessment Battery for Children (MABC), lateral
      and forward reach tests and the Timed-up and Go. RESULTS: Muscle strength
      improved in dominant side elbow flexors, hip abductors, ankle dorsiflexors and
      ankle plantarflexors (p = 0.018-0.042). Functional strength improved in seated
      throw (t = 2.7; p = 0.024), distance jump (t =  -2.8; p = 0.025) and lateral step
      up (p < 0.05). Balance improved on the MABC (t = 2.4; p = 0.040), lateral (p <
      0.05) and forward reach (p < 0.05). CONCLUSION: This feasibility study translated
      research into sustainable practice, showing that a community-based, low dose,
      group exercise program can improve the balance and strength of children with CP
      within current funding capacity. Implications for Rehabilitation It has been
      known that strength and balance training in the clinical research setting with
      specialized equipment is effective for children with CP, but this study
      demonstrates the translation of research into clinical practice in a low-cost,
      low-dose group program. Significant gains in both muscle strength and balance can
      be achieved in an eight-week community-based gym group using simple equipment.

PMID- 24564329
TI  - Filtering of MS/MS data for peptide identification.
AB  - BACKGROUND: The identification of proteins based on analysis of tandem mass
      spectrometry (MS/MS) data is a valuable tool that is not fully realized because
      of the difficulty in carrying out automated analysis of large numbers of spectra.
      MS/MS spectra consist of peaks that represent each peptide fragment, usually b
      and y ions, with experimentally determined mass to charge ratios. Whether the
      strategy employed is database matching or De Novo sequencing, a major obstacle is
      distinguishing signal from noise. Improved ability to distinguish signal peaks of
      low intensity from background noise increases the likelihood of correctly
      identifying the peptide, as valuable information is preserved while extraneous
      information is not left to mislead. RESULTS: This paper introduces an automated
      noise filtering method based on the construction of orthogonal polynomials. By
      subdividing the spectrum into a variable number (3 to 11) of bins, peaks that are
      considered "noise" are identified at a local level. Using a De Novo sequencing
      algorithm that we are developing, this filtering method was applied to a
      published dataset of more than 3000 mass spectra and an original dataset of more
      than 300 spectra. The samples were peptides from purified known proteins;
      therefore, the solutions could be compared to the correct sequences and the peaks
      corresponding to b, y and other fragments of significance could be identified.
      The same procedure was applied using two other published filtering methods. The
      ratios of the number of significant peaks that were preserved relative to the
      total number of peaks in each spectrum were determined. In the event that
      filtering out too many or too few signal peaks can lead to inaccuracy in sequence
      determination, the percentage of amino acid residues in the correct positions
      relative to the total number of amino acid residues in the correct sequence was
      also calculated for each sequence determined. CONCLUSIONS: The results show that
      an orthogonal polynomial-based method of distinguishing signal peaks from
      background in mass spectra preserves a greater portion of signal peaks than
      compared methods, improving accuracy in sequence determination.

PMID- 24564331
TI  - Val2Ala mutation in the Atp6v0a4 gene causes early-onset sensorineural hearing
      loss in children with recessive distal renal tubular acidosis: a case report.
AB  - A young female patient born to consanguineous parents was admitted to our clinic
      at the age of 3 years with a 5-month history of weight loss and recurrent urinary
      tract infections. Based on clinical findings (delayed growth and O-bein
      deformity) and laboratory tests (hypokalemia, hyperchloremia, partially
      compensated metabolic acidosis, alkaline urine and nephrocalsinosis), a diagnosis
      of distal renal tubular acidosis (dRTA) was made. Then, the audiogram revealed a
      bilateral sensorineural hearing loss (SNHL). On follow-up, bilateral SNHL
      progressively worsened requiring the need for hearing aid. The ATP6V0A4 gene
      mutation analysis showed homozygote Val2Ala mutation. To the best of our
      knowledge, this is the first report describing a Turkish girl with dRTA who
      suffered from early-onset SNHL caused by Val2Ala mutation in the ATP6V0A4 gene.

PMID- 24564330
TI  - Co-modulated behavior and effects of differentially expressed miRNA in colorectal
      cancer.
AB  - BACKGROUND: MicroRNAs (miRNAs) are short noncoding RNAs (approximately 22
      nucleotides in length) that play important roles in colorectal cancer (CRC)
      progression through silencing gene expression. Numerous dysregulated miRNAs
      simultaneously participate in the process of colon cancer development. However,
      the detailed mechanisms and biological functions of co-expressed miRNA in
      colorectal carcinogenesis have yet to be fully elucidated. RESULTS: The objective
      of this study was to identify the dysfunctional miRNAs and their target mRNAs
      using a wet-lab experimental and dry-lab bioinformatics approach. The
      differentially expressed miRNA candidates were identified from 2 miRNA profiles,
      and were confirmed in CRC clinical samples using reported target genes of
      dysfunctional miRNAs to perform functional pathway enrichment analysis. Potential
      target gene candidates were predicted by an in silico search, and their
      expression levels between normal and colorectal tumor tissues were further
      analyzed using real-time polymerase chain reaction (RT-PCR). CONCLUSION: Fifteen
      dysfunctional miRNAs were engaged in metastasis-associated pathways through
      comodulating 7 target genes, which were identified by using a multi-step
      approach. The roles of these candidate genes are worth further exploration in the
      progression of colon cancer, and could potentially be targets in future therapy.

PMID- 24564332
TI  - Hydrophilic molybdenum oxide nanomaterials with controlled morphology and strong
      plasmonic absorption for photothermal ablation of cancer cells.
AB  - The molybdenum oxide nanosheets have shown strong localized surface plasmon
      resonance (LSPR) absorption in the near-infrared (NIR) region. However, the long
      alky chains of ligands made them hydrophobic and less biocompatible. To meet the
      requirements of molybdenum based nanomaterials for use as a future photothermal
      therapy, a simple hydrothermal route has been developed for hydrophilic
      molybdenum oxide nanospheres and nanoribbons using a molybdenum precursor and
      poly(ethylene glycol) (PEG). First, molybdenum oxide nanomaterials prepared in
      the presence of PEG exhibit strong localized surface plasmon resonance (LSPR)
      absorption in near-infrared (NIR) region, compared with that of no PEG. Second,
      elevation of synthetic temperature leads to a gradual transformation of
      molybdenum oxide nanospheres into nanoribbons, entailing the evolution of an
      intense LSPR absorption in the NIR region. Third, as-prepared molybdenum oxide
      nanomaterials coated with PEG possess a hydrophilic property and thus can be
      directly used for biological applications without additional post treatments.
      Moreover, molybdenum oxide nanoribbons as a model of photothermal materials can
      efficiently convert the 980 nm wavelength laser energy into heat energy, and this
      localized hyperthermia produces the effective thermal ablation of cancer cells,
      meaning a potential photothermal material. 

PMID- 24564333
TI  - An efficient and scalable graph modeling approach for capturing information at
      different levels in next generation sequencing reads.
AB  - BACKGROUND: Next generation sequencing technologies have greatly advanced many
      research areas of the biomedical sciences through their capability to generate
      massive amounts of genetic information at unprecedented rates. The advent of next
      generation sequencing has led to the development of numerous computational tools
      to analyze and assemble the millions to billions of short sequencing reads
      produced by these technologies. While these tools filled an important gap,
      current approaches for storing, processing, and analyzing short read datasets
      generally have remained simple and lack the complexity needed to efficiently
      model the produced reads and assemble them correctly. RESULTS: Previously, we
      presented an overlap graph coarsening scheme for modeling read overlap
      relationships on multiple levels. Most current read assembly and analysis
      approaches use a single graph or set of clusters to represent the relationships
      among a read dataset. Instead, we use a series of graphs to represent the reads
      and their overlap relationships across a spectrum of information granularity. At
      each information level our algorithm is capable of generating clusters of reads
      from the reduced graph, forming an integrated graph modeling and clustering
      approach for read analysis and assembly. Previously we applied our algorithm to
      simulated and real 454 datasets to assess its ability to efficiently model and
      cluster next generation sequencing data. In this paper we extend our algorithm to
      large simulated and real Illumina datasets to demonstrate that our algorithm is
      practical for both sequencing technologies. CONCLUSIONS: Our overlap graph
      theoretic algorithm is able to model next generation sequencing reads at various
      levels of granularity through the process of graph coarsening. Additionally, our
      model allows for efficient representation of the read overlap relationships, is
      scalable for large datasets, and is practical for both Illumina and 454
      sequencing technologies.

PMID- 24564334
TI  - Epidemiology and treatment outcomes of diabetic retinopathy in a diabetic
      population from Cameroon.
AB  - BACKGROUND: Diabetic retinopathy (DR) is the most common microvascular
      complication of diabetes. It can lead to significant visual loss. The aim of this
      study was to determine the frequency and clinical profile of diabetic
      retinopathy, and assess the outcomes of laser photocoagulation therapy in a
      diabetic population in Cameroon. METHODS: We carried out a prospective cohort
      study during 24 months in the Department of Ophthalmology of the Douala General
      Hospital, Cameroon. We included all diabetic patients who were referred from
      diabetes clinics for ophthalmologic evaluation. Data included type and duration
      of diabetes, visual acuity, intra-ocular pressure, results of fundoscopy and
      fluorescein angiography, and outcomes two months after treatment with laser
      photocoagulation. RESULTS: We included 407 patients; 88% had type 2 diabetes.
      Their mean duration of diabetes was 6.4 years (SD=6.6). Forty point three percent
      (164/407) of patients were found to have DR on fundoscopy. Of the 164 patients
      with DR, 63.4% (104/164) had non-proliferative and 36.6% (60/164) had
      proliferative DR. Diabetic maculopathy was found in 14.5% (59/407) of all
      participants, and 36% (59/164) of patients with DR. There was a strong
      correlation between the duration of diabetes and retinopathy status (p < 0.001, r
      = 0.9541). Overall, 17.4% (71/407) of patients were eligible for laser
      photocoagulation. Of these, 66.2% (47/71) were treated, and 78.7% (37/47) of
      treated patients came back for control two months later. Among these treated
      patients an improvement of the retinopathy was noted in 73% (27/37), no change in
      16.2% (6/37) and a worsening in 10.8% (4/37). Severe proliferative DR was
      significantly associated with treatment failure (p < 0.001). CONCLUSIONS: The
      frequency of DR may be high among diabetic patients in Cameroon. There was a good
      uptake of laser photocoagulation therapy among patients affected by DR in our
      setting, with good treatment outcomes. Interventions to prevent diabetes and
      increase the precocity of diagnosis and treatment of DR should be scaled up.

PMID- 24564335
TI  - iVUN: interactive Visualization of Uncertain biochemical reaction Networks.
AB  - BACKGROUND: Mathematical models are nowadays widely used to describe biochemical
      reaction networks. One of the main reasons for this is that models facilitate the
      integration of a multitude of different data and data types using parameter
      estimation. Thereby, models allow for a holistic understanding of biological
      processes. However, due to measurement noise and the limited amount of data,
      uncertainties in the model parameters should be considered when conclusions are
      drawn from estimated model attributes, such as reaction fluxes or transient
      dynamics of biological species. METHODS AND RESULTS: We developed the visual
      analytics system iVUN that supports uncertainty-aware analysis of static and
      dynamic attributes of biochemical reaction networks modeled by ordinary
      differential equations. The multivariate graph of the network is visualized as a
      node-link diagram, and statistics of the attributes are mapped to the color of
      nodes and links of the graph. In addition, the graph view is linked with several
      views, such as line plots, scatter plots, and correlation matrices, to support
      locating uncertainties and the analysis of their time dependencies. As
      demonstration, we use iVUN to quantitatively analyze the dynamics of a model for
      Epo-induced JAK2/STAT5 signaling. CONCLUSION: Our case study showed that iVUN can
      be used to perform an in-depth study of biochemical reaction networks, including
      attribute uncertainties, correlations between these attributes and their
      uncertainties as well as the attribute dynamics. In particular, the linking of
      different visualization options turned out to be highly beneficial for the
      complex analysis tasks that come with the biological systems as presented here.

PMID- 24564336
TI  - ProphNet: a generic prioritization method through propagation of information.
AB  - BACKGROUND: Prioritization methods have become an useful tool for mining large
      amounts of data to suggest promising hypotheses in early research stages.
      Particularly, network-based prioritization tools use a network representation for
      the interactions between different biological entities to identify novel indirect
      relationships. However, current network-based prioritization tools are strongly
      tailored to specific domains of interest (e.g. gene-disease prioritization) and
      they do not allow to consider networks with more than two types of entities (e.g.
      genes and diseases). Therefore, the direct application of these methods to
      accomplish new prioritization tasks is limited. RESULTS: This work presents
      ProphNet, a generic network-based prioritization tool that allows to integrate an
      arbitrary number of interrelated biological entities to accomplish any
      prioritization task. We tested the performance of ProphNet in comparison with
      leading network-based prioritization methods, namely rcNet and DomainRBF, for
      gene-disease and domain-disease prioritization, respectively. The results
      obtained by ProphNet show a significant improvement in terms of sensitivity and
      specificity for both tasks. We also applied ProphNet to disease-gene
      prioritization on Alzheimer, Diabetes Mellitus Type 2 and Breast Cancer to
      validate the results and identify putative candidate genes involved in these
      diseases. CONCLUSIONS: ProphNet works on top of any heterogeneous network by
      integrating information of different types of biological entities to rank
      entities of a specific type according to their degree of relationship with a
      query set of entities of another type. Our method works by propagating
      information across data networks and measuring the correlation between the
      propagated values for a query and a target sets of entities. ProphNet is
      available at: http://genome2.ugr.es/prophnet. A Matlab implementation of the
      algorithm is also available at the website.

PMID- 24564337
TI  - Dietary vitamin D supplementation does not reduce the incidence or severity of
      asbestos-induced mesothelioma in a mouse model.
AB  - Epidemiological studies suggest that vitamin and mineral intake is associated
      with cancer incidence. A prevention strategy based on diet or dietary
      supplementation could have enormous benefit, both directly, by preventing
      disease, and indirectly by alleviating fear in millions of people worldwide who
      have been exposed to asbestos. We have previously shown that dietary
      supplementation with the antioxidants vitamins A, E, and selenium does not affect
      overall survival nor the time to progression of asbestos-induced mesothelioma in
      MexTAg mice. Here we have extended our analysis to vitamin D. We compared
      survival of asbestos-exposed MexTAg mice provided with diets that were deficient
      or supplemented with 4500 IU/kg vitamin D (cholecalciferol). Survival of
      supplemented mice was significantly shorter than mice given a standard AIN93 diet
      containing 1000 IU/kg cholecalciferol (median survival was 29 and 32.5 weeks
      respectively). However, mice deficient in vitamin D had the same rate of
      mesothelioma development as control mice. Neither the latency time from asbestos
      exposure to diagnosis nor disease progression after diagnosis were significantly
      different between mice on these diets. We conclude that vitamin D is unlikely to
      moderate the incidence of disease in asbestos-exposed populations or to
      ameliorate the pathology in patients with established mesothelioma. 

PMID- 24564338
TI  - Extensive conformational heterogeneity within protein cores.
AB  - Basic principles of statistical mechanics require that proteins sample an
      ensemble of conformations at any nonzero temperature. However, it is still common
      to treat the crystallographic structure of a protein as the structure of its
      native state, largely because high-resolution structural characterization of
      protein flexibility remains a profound challenge. To assess the typical degree of
      conformational heterogeneity within folded proteins, we construct Markov state
      models describing the thermodynamics and kinetics of proteins ranging from 72 to
      263 residues in length. Each of these models is built from hundreds of
      microseconds of atomically detailed molecular dynamics simulations. Examination
      of the side-chain degrees of freedom reveals that almost every residue visits at
      least two rotameric states over this time frame, with rotamer transition rates
      spanning a wide range of time scales (from nanoseconds to tens of microseconds).
      We also report substantial backbone dynamics on time scales longer than are
      typically addressed by experimental measures of protein flexibility, such as NMR
      order parameters. Finally, we demonstrate that these extensive rearrangements are
      consistent with NMR and crystallographic data, which supports the validity of our
      models. Altogether, these results depict the interior of proteins not as well
      ordered solids, as is often imagined, but instead as dense fluids, which undergo
      substantial structural fluctuations despite their high packing fraction. 

PMID- 24564339
TI  - A review of xylan and lignin biosynthesis: foundation for studying Arabidopsis
      irregular xylem mutants with pleiotropic phenotypes.
AB  - Plant cells are surrounded by a carbohydrate-rich extracellular matrix known as
      the cell wall. Primary cell walls are laid down around dividing and elongating
      cells and consist largely of the polysaccharides cellulose, hemicelluloses, and
      pectin along with approximately 10% protein. Specific cells such as xylem vessels
      and fibers lay down a secondary wall rich in cellulose, hemicellulose, and
      lignin, with lesser amounts of pectin. Most of the models depict the plant cell
      wall as a matrix of separate polysaccharides. However, the recent identification
      of a proteoglycan that contains covalently attached pectin and xylan indicates
      that at least some of these wall glycans exist as domains within a single
      glycopolymer and that current models of the wall need to be revised. Furthermore,
      several cell wall biosynthesis mutants, including the secondary cell wall mutant
      irregular xylem (irx) 8, are affected in multiple cell wall polymers making it
      challenging to define the biochemical function of the mutated gene. The goal of
      this review is to provide a background for studying genes which encode secondary
      cell wall biosynthetic proteins whose mutation affects multiple wall polymers
      including xylan and lignin. We first review the phenotypes of the irx mutants and
      then summarize the current understanding of the structure and synthesis of xylan
      and lignin along with a review of transcription factors known to affect secondary
      wall synthesis. This review is intended to serve as a resource for those studying
      genes that encode proteins involved in the synthesis of plant secondary wall
      lignin and xylan.

PMID- 24564341
TI  - Using LiST to model potential reduction in under-five mortality in Burkina Faso.
AB  - BACKGROUND: Under-five mortality remains high in Burkina Faso with significant
      reductions required to meet Millennium Development Goal 4. The Acceleration for
      Maternal, Newborn, and Child Health is being implemented to reduce child
      mortality in the North and Center North regions of Burkina Faso. METHODS: The
      Lives Saved Tool was used to determine the percent reduction in child mortality
      that can be achieved given baseline levels of coverage for interventions targeted
      by the Acceleration. Data were obtained from the Demographic and Health Survey
      2003, the Multiple Indicator Cluster Survey 2006, and the baseline survey for the
      program from 2010. In addition to the scale up, scenarios were generated to
      examine the outcome if secular trends in intervention coverage change persisted
      and if intervention coverage levels remained constant. RESULTS: Scaling up all
      interventions to their target coverage level showed a potential reduction in
      under-five mortality of 22 percent, with district specific reductions in
      mortality ranging from 14 to 25 percent. The percent reduction in under-five
      mortality that might be attributable to the program was 16 percent and varied
      between 14 and 19 percent by district. Treatment of diarrhea with ORS and malaria
      with ACTs accounted for the majority of the reduction in mortality. CONCLUSIONS:
      These findings suggest that significant reductions in under-five mortality may be
      achieved through the scale-up of the Acceleration. The Ministry of Health and its
      partners in Burkina Faso should continue their efforts to scale up these proven
      interventions to achieve and even exceed target levels for coverage.

PMID- 24564340
TI  - Vaccine against tuberculosis: what's new?
AB  - BACKGROUND: one of the World Health Organization Millennium Development Goal is
      to reduce tuberculosis incidence by 2015. However, more of 8.5 million
      tuberculosis cases have been reported in 2011, with an increase of multidrug
      resistant strains. Therefore, the World Health Organization target cannot be
      reach without the help of a vaccine able to limit the spread of tuberculosis.
      Nowadays, bacille Calmette-Guerin is the only vaccine available against
      tuberculosis. It prevents against meningeal and disseminated tuberculosis in
      children, but its effectiveness against pulmonary form in adolescents and adults
      is argued. METHOD: a systematic review was performed by searches of Pubmed,
      references of the relevant articles and Aeras and ClinicalTrial.gov websites.
      RESULTS: 100 articles were included in this review. Three viral vectored booster
      vaccines, five protein adjuvant booster vaccines, two priming vaccines and two
      therapeutic vaccines have been analyzed. CONCLUSIONS: Several vaccines are in the
      pipeline, but further studies on basic research, clinical trial and mass
      vaccination campaigns are needed to achieve the TB eradication target by 2050.

PMID- 24564342
TI  - Imaging early endothelial inflammation following stroke by core shell silica
      superparamagnetic glyconanoparticles that target selectin.
AB  - Activation of the endothelium is a pivotal first step for leukocyte migration
      into the diseased brain. Consequently, imaging this activation process is highly
      desirable. We synthesized carbohydrate-functionalized magnetic nanoparticles that
      bind specifically to the endothelial transmembrane inflammatory proteins E and P
      selectin. Magnetic resonance imaging revealed that the targeted nanoparticles
      accumulated in the brain vasculature following acute administration into a
      clinically relevant animal model of stroke, though increases in selectin
      expression were observed in both brain hemispheres. Nonfunctionalized naked
      particles also appear to be a plausible agent to target the ischemic vasculature.
      The importance of these findings is discussed regarding the potential for
      translation into the clinic. 

PMID- 24564343
TI  - Supporting trauma-informed recovery care through clinical feedback in community
      mental health research.
AB  - OBJECTIVE: The present study evaluated the feasibility of integrating a clinical
      feedback mechanism into trauma-focused psychosocial recovery research. METHODS:
      Ethnoculturally diverse mental health consumers (N = 172) participating in a
      study of trauma and posttraumatic stress disorder were provided the option to
      have their personal research data disclosed to their treatment providers to guide
      recovery treatment. RESULTS: The majority of consumers (68%) requested that
      researchers disclose their personal trauma information to their treatment
      providers. Disclosure rates were similar across gender and racial background;
      however, rates were significantly higher for consumers exposed versus not exposed
      to childhood sexual abuse (81% vs. 64%, respectively). CONCLUSIONS AND
      IMPLICATIONS FOR PRACTICE: Study findings suggest that consumers are open to
      sharing sensitive information collected during research participation including
      history of trauma exposure and trauma-related difficulties with recovery
      providers, and support the viability of incorporating individualized clinical
      feedback into trauma research to promote recovery care.

PMID- 24564344
TI  - Assertive community treatment for parents with serious mental illnesses: a
      comparison of "parent-sensitive" assertive community treatment teams versus other
      teams.
AB  - OBJECTIVE: Assertive Community Treatment (ACT) is an evidence-based practice for
      individuals living with serious mental illnesses. Although studies estimate that
      at least half of people with serious mental illnesses are parents, little is
      known about ACT policies and services for parent consumers. METHOD: Seventy-three
      ACT providers from 67 teams completed a survey about treatment services for
      parent consumers. Teams were divided into "parent-sensitive" and "nonsensitive"
      teams based on 3 indicators of parent-related services: identifying parental
      status, discussing parenting issues, and assisting with parenting needs. For each
      treatment indicator, teams were compared to determine factors that may contribute
      to parent-supportive services. RESULTS: Providers from parent-sensitive teams
      that consistently identified consumers' parental status were more likely to talk
      with consumers about committed relationships and to assist consumers with parent
      child communication. Parent-sensitive teams that frequently discussed parenting
      issues with consumers were less likely to be unsure of consumers' family plans,
      more likely to find out about parenting during goal setting, and more likely to
      assist with parent-related needs. Parent-sensitive teams that frequently provided
      assistance with parenting needs were more likely to serve minority consumers and
      consumers who want children, spend more time discussing parenting issues, and
      offer special programs for parent consumers. CONCLUSIONS AND IMPLICATIONS FOR
      PRACTICE: Findings suggest that simply identifying consumers as parents is not
      sufficient for ensuring consistent provision of parent-supportive services,
      whereas discussing parenting issues is associated with increased service
      provision. More intensive, evidence-based parent-supportive services are needed,
      as well as continued research on parents with serious mental illnesses and
      available treatment services. (PsycINFO Database Record (c) 2014 APA, all rights
      reserved).

PMID- 24564345
TI  - Sorting genomes with rearrangements and segmental duplications through trajectory
      graphs.
AB  - We study the problem of sorting genomes under an evolutionary model that includes
      genomic rearrangements and segmental duplications. We propose an iterative
      algorithm to improve any initial evolutionary trajectory between two genomes in
      terms of parsimony. Our algorithm is based on a new graphical model, the
      trajectory graph, which models not only the final states of two genomes but also
      an existing evolutionary trajectory between them. We show that redundant
      rearrangements in the trajectory correspond to certain cycles in the trajectory
      graph, and prove that our algorithm converges to an optimal trajectory for any
      initial trajectory involving only rearrangements. 

PMID- 24564346
TI  - Are 'leaky gut' and behavior associated with gluten and dairy containing diet in
      children with autism spectrum disorders?
AB  - OBJECTIVES: Studies have suggested a link between diet and behavior in children
      with autism spectrum disorders (ASDs). Parental reports of behavioral changes
      upon exposure to gluten and/or casein are common in clinical practice. An
      association between diet type, intestinal permeability (IP) ('leaky gut'), and
      behavior has been long proposed but not substantiated. We explored this possible
      association in this trial. METHODS: This randomized double-blind, placebo
      controlled study explored the effects of gluten and milk on IP and behavior in
      children with ASDs over a period of 4 weeks. IP assessed by lactulose:mannitol
      (L/M) sugar permeability test and behavior assessed by the Aberrant Behavior
      Checklist and Conners Parent Rating were measured. Gastrointestinal symptoms in
      both groups were also monitored. RESULTS: Neither the L/M ratio nor behavioral
      scores were different between groups exposed to gluten/dairy or placebo. The
      changes observed were noted to be small and not clinically significant.
      DISCUSSION: Our study although underpowered to show small differences does not
      support an association between dietary gluten/milk, IP, and behavioral changes in
      subjects with ASD.

PMID- 24564347
TI  - The application of polymerized porcine hemoglobin (pPolyHb) in the rat small
      bowel preservation.
AB  - Small bowel transplantation (SBTx) has become a standard clinical treatment for
      short bowel syndrome or irreversible intestinal function failure. Optimum
      preservation of the organ is essential for the success of transplantation. In
      this study, pPolyHb was used as an additive to hypertonic citrate adenine
      solution (HCA) to provide oxygen for rat small bowel transplant. Rat small bowels
      were preserved in HCA, HCA with pPolyHb, and University of Wisconsin solution
      (UW) for 12, 24, and 36 h, respectively. The results suggested that the
      preservation effect of HCA with pPolyHb was comparable with the UW solution, and
      more effective than the HCA solution.

PMID- 24564348
TI  - Nanotechnology: a magic bullet for HIV AIDS treatment.
AB  - Human immunodeficiency virus (HIV) infection has become devastating in last a few
      years. Nearly 7400 new infection cases are coming every day. Highly active
      antiretroviral therapy (HAART), which involves combination of at least three
      antiretroviral (ARV) drugs, has been used to extend the life span of the HIV
      infected patients. HAART has played an important role to reduce mortality rate in
      the developed countries but in the developing countries condition is still worst
      with millions of people being infected by this disease. For the improvement of
      the situation, nanotechnology-based drug system has been explored for the HIV
      therapeutics. Nanosystems used for HIV therapeutics offer some unique advantage
      like enhancement of bioavailability, water solubility, stability, and targeting
      ability of ARV drugs. Main nanotechnology-based systems explored for HIV
      therapeutics are liposomes, nanoparticles, niosomes, polymeric micelles, and
      dendrimers. Present manuscript reviews conventional method of HIV therapeutics
      and recent advances in the field of nanotechnology-based systems for treatment of
      HIV-AIDS.

PMID- 24564349
TI  - Fibronectin-Alginate microcapsules improve cell   viability and protein secretion
      of encapsulated   Factor IX-engineered human mesenchymal   stromal cells.
AB  - Continuous delivery of proteins by engineered cells encapsu-lated in
      biocompatible polymeric microcapsules is of considerable therapeutic potential.
      However, this technology has not lived up to expectations due to inadequate cell-
      matrix interactions and subsequent cell death. In this study we hypoth-esize that
      the presence of fibronectin in an alginate matrix may enhance the viability and
      functionality of encapsulated human cord blood-derived mesenchymal stromal cells
      (MSCs) expressing the human Factor IX (FIX) gene. MSCs were encapsulated in
      alginate-PLL microcapsules containing 10, 100, or 500 MUg/ml fibronectin to
      ameliorate cell survival. MSCs in microcapsules with 100 and 500 MUg/ml
      fibronectin demonstrated improved cell viability and proliferation and higher FIX
      secretion compared to MSCs in non-supplemented microcapsules. In contrast, 10
      MUg/ml fibronectin did not significantly affect the viability and protein
      secretion from the encapsulated cells. Differentiation studies demonstrated
      osteogenic (but not chondrogenic or adipogenic) differentiation capability and
      efficient FIX secretion of the enclosed MSCs in the fibronectin-alginate
      suspension culture. Thus, the use of recombinant MSCs encapsulated in fibronectin
      alginate microcapsules in basal or osteogenic cultures may be of practical use in
      the treatment of hemophilia B.

PMID- 24564350
TI  - Vesicular system: Versatile carrier for transdermal delivery of bioactives.
AB  - The transdermal route of drug delivery has gained immense interest for
      pharmaceutical researchers. The major hurdle for diffusion of drugs and
      bioactives through transdermal route is the stratum corneum, the outermost layer
      of the skin. Currently, various approaches such as physical approach, chemical
      approach, and delivery carriers have been used to augment the transdermal
      delivery of bioactives. This review provides a brief overview of mechanism of
      drug transport across skin, different lipid vesicular systems, with special
      emphasis on lipid vesicular systems including transfersomes, liposomes, niosomes,
      ethosomes, virosomes, and pharmacosomes and their application for the delivery of
      different bioactives. 

PMID- 24564351
TI  - Preliminary pharmacokinetics of PEGylated oxaliplatin polylactic acid
      nanoparticles in rabbits and tumor-bearing mice.
AB  - To testify the targeting effect of PEGylated Oxaliplatin polylactic acid (OP-PEG
      PLA) nanoparticles (NPs), we studied drug concentration in rabbit plasma and
      tissue distribution in tumor-bearing mice. Concentration of nanoparticle
      colloidal solution was performed with dialysis. Qualities of enriched NPs were
      characterized by particle size and drug content. OP concentration in samples was
      detected using ICP-MS. Compared to OP solution groups, OP concentration of NPs
      groups increased in the tumor (p < 0.05) and decreased in the kidney and heart (p
      < 0.05). Compared to OP-PLA NPs groups, OP concentration of OP-PEG-PLA NPs groups
      increased in the tumor and decreased in the liver and lung (p < 0.05). The
      concentrated OP-PEG-PLA NPs are good in clinical application and tumor delivery. 

PMID- 24564353
TI  - Binding of a protein or a small polyelectrolyte onto synthetic vesicles.
AB  - Catanionic vesicles were prepared by mixing nonstoichiometric amounts of sodium
      bis(2-ethylhexyl) sulfosuccinate and dioctyldimethylammonium bromide in water.
      Depending on the concentration and mole ratios between the surfactants,
      catanionic vesicular aggregates are formed. They have either negative or positive
      charges in excess and are endowed with significant thermodynamic and kinetic
      stability. Vesicle characterization was performed by dynamic light scattering and
      electrophoretic mobility. It was inferred that vesicle size scales in inverse
      proportion with its surface charge density and diverges as the latter quantity
      approaches zero and/or the mole ratio equals unity. Therefore, both variables are
      controlled by the anionic/cationic mole ratio. Small-angle X-ray scattering, in
      addition, indicates that vesicles are unilamellar. Selected anionic vesicular
      systems were reacted with poly-L-lysine hydrobromide or lysozyme. Polymer binding
      continues until complete neutralization of the negatively charged sites on the
      vesicles surface is attained, as inferred by electrophoretic mobility. Lipoplexes
      are formed as a result of significant electrostatic interactions between cationic
      polyelectrolytes and negatively charged vesicles.

PMID- 24564354
TI  - Synthesis and properties of butterfly-shaped expanded naphthofuran derivatives.
AB  - The construction of dinaphtho[2,1-b;2',3'-d]furan-6-ol was developed via a
      dehydration reaction involving two molecules of 2,3-dihydroxynaphthalene in the
      presence of a strong acid. Starting from the dinaphthofuran, a variety of
      butterfly shaped derivatives were synthesized. The optical properties of these
      compounds were investigated with special attention to the dihedral angle formed
      by adjacent dinaphthofuran rings and/or the sizes of the fused aromatic rings. 

PMID- 24564355
TI  - Fragmented carbon nanotube macrofilms as adhesive conductors for lithium-ion
      batteries.
AB  - Polymer binders such as poly(vinylidene fluoride) (PVDF) and conductive additives
      such as carbon black (CB) are indispensable components for manufacturing battery
      electrodes in addition to active materials. The concept of adhesive conductors
      employing fragmented carbon nanotube macrofilms (FCNTs) is demonstrated by
      constructing composite electrodes with a typical active material, LiMn2O4. The
      adhesive FCNT conductors provide not only a high electrical conductivity but also
      a strong adhesive force, functioning simultaneously as both the conductive
      additives and the binder materials for lithium-ion batteries. Such composite
      electrodes exhibit superior high-rate and retention capabilities compared to the
      electrodes using a conventional binder (PVDF) and a conductive additive (CB). An
      in situ tribology method combining wear track imaging and force measurement is
      employed to evaluate the adhesion strength of the adhesive FCNT conductors. The
      adhesive FCNT conductors exhibit higher adhesion strength than PVDF. It has
      further been confirmed that the adhesive FCNT conductor can be used in both
      cathodes and anodes and is proved to be a competent substitute for polymer
      binders to maintain mechanical integrity and at the same time to provide
      electrical connectivity of active materials in the composite electrodes. The
      organic-solvent-free electrode manufacturing offers a promising strategy for the
      battery industry. 

PMID- 24564352
TI  - Genome sequencing of high-penicillin producing industrial strain of Penicillium
      chrysogenum.
AB  - BACKGROUND: Due to the importance of Penicillium chrysogenum holding in medicine,
      the genome of low-penicillin producing laboratorial strain Wisconsin54-1255 had
      been sequenced and fully annotated. Through classical mutagenesis of Wisconsin54
      1255, product titers and productivities of penicillin have dramatically
      increased, but what underlying genome structural variations is still little
      known. Therefore, genome sequencing of a high-penicillin producing industrial
      strain is very meaningful. RESULTS: To reveal more insights into the genome
      structural variations of high-penicillin producing strain, we sequenced an
      industrial strain P. chrysogenum NCPC10086. By whole genome comparative analysis,
      we observed a large number of mutations, insertions and deletions, and structural
      variations. There are 69 new genes that not exist in the genome sequence of
      Wisconsin54-1255 and some of them are involved in energy metabolism, nitrogen
      metabolism and glutathione metabolism. Most importantly, we discovered a 53.7 Kb
      "new shift fragment" in a seven copies of determinative penicillin biosynthesis
      cluster in NCPC10086 and the arrangement type of amplified region is unique.
      Moreover, we presented two large-scale translocations in NCPC10086, containing
      genes involved energy, nitrogen metabolism and peroxysome pathway. At last, we
      found some non-synonymous mutations in the genes participating in homogentisate
      pathway or working as regulators of penicillin biosynthesis. CONCLUSIONS: We
      provided the first high-quality genome sequence of industrial high-penicillin
      strain of P. chrysogenum and carried out a comparative genome analysis with a low
      producing experimental strain. The genomic variations we discovered are related
      with energy metabolism, nitrogen metabolism and so on. These findings demonstrate
      the potential information for insights into the high-penicillin yielding
      mechanism and metabolic engineering in the future.

PMID- 24564356
TI  - Lost in translation: exploring therapists' experiences of providing stroke
      rehabilitation across a language barrier.
AB  - PURPOSE: This study sought to explore English-speaking therapists' experiences of
      providing stroke rehabilitation to non-English speaking individuals in an urban
      area. METHODS: This was a qualitative study using focus groups. Two focus groups
      were conducted. Participants included physiotherapists, occupational therapists,
      speech and language therapists and a psychotherapist (n = 13). A grounded theory
      approach was used to analyse data. RESULTS: Factors affecting rehabilitation were
      categorised under themes of engagement, practicalities and social context. Subtle
      communication was identified as a core category that ran through all themes,
      illustrating therapists' use and interpretation of subtleties and nuances which a
      language barrier impeded. Providing rehabilitation across a language barrier was
      found to present significant challenges. Therapists perceived that assessment and
      treatment are likely to be delayed and limited in scope, especially regarding
      cognition and neurological communication disorders. A conceptual model of factors
      involved in rehabilitation across a language barrier was generated. CONCLUSIONS:
      Therapists perceive that rehabilitation is affected by a language barrier. The
      conceptual model illustrates the interrelationship between factors affecting
      rehabilitation provision when there is a language barrier. Subtle communication
      was found to be an important therapeutic tool which was lost across a language
      barrier, and may have broader relevance to therapeutic relationships in the field
      of rehabilitation. Further research is needed to gain insights into experiences
      of individuals receiving rehabilitation across a language barrier and to identify
      how to enhance the efficacy of rehabilitation for them. IMPLICATIONS FOR
      REHABILITATION: As it appears rehabilitation is affected by a language barrier,
      this is likely to impact on the outcome of an individual's rehabilitation. The
      concept of "subtle communication" should be recognised as a vital component of
      therapeutic skills. Improving access to formal interpreters, extending their role
      and introducing training could reduce practical barriers. The conceptual model
      could be utilised by clinicians as a tool for reflection or education.

PMID- 24564357
TI  - Parallels and problems of normalization in rehabilitation and universal design:
      enabling connectivities.
AB  - PURPOSE: Universal design (UD) is oriented to creating products, buildings,
      outdoor spaces and services for use by all people to the fullest extent possible
      according to principles of enabling equal citizenship. Nevertheless its
      theoretical basis has been under-explored, a critique that has also been leveled
      at rehabilitation. This commentary explores parallels between UD and dominant
      rehabilitation discourses that risk privileging or discrediting particular ways
      of being and doing. METHODS: Commentary. RESULTS: Drawing from examples that
      explore the intersection of bodies, places and technologies with disabled people,
      I examined how practices of normalization risk reproducing the universalized body
      and legitimated forms of mobility, and in so doing perpetuates the "othering" of
      difference. To address these limitations, I explored the postmodern notion of
      multiple creative "assemblages" that are continually made and broken over time
      and space. Assemblages resist normalization tendencies by acknowledging and
      fostering multiple productive dependencies between human and non-human elements
      that include diverse bodies, not just those labeled disabled. CONCLUSION: In
      exploring the potential of enhancing creative assemblages and multiple
      dependencies, space opens up in UD and rehabilitation for acknowledging,
      developing, and promoting a multiplicity of bodily forms and modes of mobility.
      Implications for Rehabilitation Universal design and rehabilitation both risk
      perpetuating particular ideas about what disabled people should be, do, and
      value, that privilege a limited range of particular bodily forms. The notion of
      "assemblages" provides a conceptual tool for rethinking negative views of
      dependence and taken for granted independence goals. In exploring the potential
      of enhancing various dependencies, space opens up for reconsidering disability,
      mobility and multiple ways of "doing-in-the-world".

PMID- 24564358
TI  - Health behaviour change theories: contributions to an ICF-based behavioural
      exercise therapy for individuals with chronic diseases.
AB  - PURPOSE: The purpose of this perspective is (1) to incorporate recent
      psychological health behaviour change (HBC) theories into exercise therapeutic
      programmes, and (2) to introduce the International Classification of Functioning
      (ICF)-based concept of a behavioural exercise therapy (BET). METHODS: Relevant
      personal modifiable factors of physical activity (PA) were identified based on
      three recent psychological HBC theories. Following the principles of intervention
      mapping, a matrix of proximal programme objectives specifies desirable parameter
      values for each personal factor. As a result of analysing reviews on behavioural
      techniques and intervention programmes of the German rehabilitation setting, we
      identified exercise-related techniques that impact the personal determinants.
      Finally, the techniques were integrated into an ICF-based BET concept. RESULTS:
      Individuals' attitudes, skills, emotions, beliefs and knowledge are important
      personal factors of PA behaviour. BET systematically addresses these personal
      factors by a systematic combination of adequate exercise contents with related
      behavioural techniques. The presented 28 intervention techniques serve as a
      theory-driven "tool box" for designing complex BET programmes to promote PA.
      CONCLUSION: The current paper highlights the usefulness of theory-based
      integrative research in the field of exercise therapy, offers explicit methods
      and contents for physical therapists to promote PA behaviour, and introduces the
      ICF-based conceptual idea of a BET. Implications for Rehabilitation Irrespective
      of the clients' indication, therapeutic exercise programmes should incorporate
      effective, theory-based approaches to promote physical activity. Central
      determinants of physical activity behaviour are a number of personal factors:
      individuals' attitudes, skills, emotions, beliefs and knowledge. Clinicians
      implementing exercise therapy should set it within a wider theoretical framework
      including the personal factors that influence physical activity. To increase
      exercise-adherence and promote long-term physical activity behaviour change, the
      concept of a behavioural exercise therapy (BET) offers a theory-based approach to
      systematically address relevant personal factors with a combination of adequate
      contents of exercise with exercise-related techniques of behaviour change.

PMID- 24564359
TI  - Representations of disability and normality in rehabilitation technology
      promotional materials.
AB  - PURPOSE: To explore the ways in which promotional materials for two
      rehabilitation technologies reproduce commonly held perspectives about disability
      and rehabilitation. METHOD: Our analysis was informed by critical disability
      studies using techniques from discourse analysis to examine texts (words and
      images) and their relation to social practices and power. Using this approach,
      promotional materials for (a) hearing aid and (b) robotic gait training
      technologies were interrogated using three central questions: (1) Who are
      represented? (2) What is promised? and (3) Who has authority? RESULTS: Messages
      of normalization pervaded representations of disabled children and their
      families, and the promises offered by the technologies. The latter included
      efficiency and effectiveness, progress and improvement, success and inclusion,
      and opportunities for a normal life. CONCLUSIONS: Normalization discourses
      construct childhood disability through texts and images. These discourses
      reinforce pervasive negative messages about disability that are taken up by
      children and families and have ethical implications for clinical practice.
      Rehabilitation has largely focused on "fixing" the individual, whereas broadening
      the clinical gaze to the social dimensions of disablement may lead to a more
      sensitive and informed approach within family-clinician discussions surrounding
      these advanced technologies and the use they make of promotional materials.
      Implications for Rehabilitation Awareness of the potential effects of implicit
      and explicit messages about disability in promotional materials may lead to a
      more sensitive and informed approach within family-clinician discussions
      surrounding rehabilitation technologies. In practice, it is important for
      rehabilitation professionals to remember that parents' and children's values and
      beliefs are shaped over time, and parents' and professionals' perspectives on
      disability strongly influence how disabled children internalize what disability
      means to them.

PMID- 24564360
TI  - Religious faith and self-efficacy among stroke patients in Kuwait: health
      professionals' views.
AB  - PURPOSE: This study explored health professionals' views about the influence of
      Muslim religious beliefs on Kuwaiti patients' self-efficacy within stroke
      rehabilitation. It also explored their confidence in discussing religious issues
      with patients during rehabilitation. METHOD: Qualitative semi-structured
      interviews were conducted with 10 expatriate health professionals of various
      religious faiths working in stroke rehabilitation (five nurses, four
      physiotherapists and one physician). Data were analysed thematically. FINDINGS:
      Health professionals considered that self-efficacy in stroke rehabilitation was
      strengthened by patients' feelings of partnership with God, which evoked hope and
      strength by retaining continuity of the moral self, and by viewing disability as
      a test of resilience. Fatalistic beliefs and the belief that stroke is a
      punishment from God were thought to undermine self-efficacy. Health professionals
      sought to foster patients' experience of religious empowerment by using religious
      phrases during rehabilitation, and encouraging religious observance. Nurse
      participants considered that discussing religious issues with their patients was
      intrinsic to culturally competent care. CONCLUSIONS: It is known that patients'
      self-efficacy in rehabilitation can be strengthened through a number of
      strategies such as goal-setting and feedback. This study suggests that for Muslim
      patients in Kuwait, health professionals also need to be mindful of their need
      for religious empowerment. Implications for Rehabilitation Muslim religious
      beliefs may influence self-efficacy in stroke patients in the Kuwaiti context.
      Patients who regard themselves as working in partnership with their God may feel
      empowered and more confident to achieve goals in rehabilitation. Patients who
      regard their stroke as a divine punishment may have lower self-efficacy. Health
      professionals might support religious patients to retain a sense of their
      unimpaired moral selves (e.g. by enabling religious observance) as a means of
      enhancing self-efficacy in rehabilitation.

PMID- 24564361
TI  - Weather, disability, vulnerability, and resilience: exploring how youth with
      physical disabilities experience winter.
AB  - PURPOSE: Having a mobility-related disability can create numerous challenges in
      navigating the physical and built environment, especially during winter. Such
      weather-related challenges can be a significant barrier to participation in
      everyday activities and are linked with increased physical and psychological
      morbidities. Unfortunately, mobility research--especially among youth - has often
      overlooked the effects of winter weather. METHODS: This study explores the
      experiences of daily activities during Canadian winter among a purposive sample
      of youth, aged 15-22, who have a physical disability requiring the use of a
      mobility device. The researchers applied a qualitative design, including 12 in
      depth interviews. RESULTS: Our findings show that youth encounter several
      vulnerabilities to participating in social and recreational activities in winter,
      including: (1) physical barriers and social spatial exclusion; (2) health and
      safety concerns; and (3) psychosocial issues (i.e., worry, isolation and
      dependence). Youth also discussed several strategies for adapting to barriers and
      enhancing their participation during winter, including: (1) wheelchair
      maintenance; (2) awareness of surroundings; (3) practice using mobility devices
      and planning; and (4) keeping busy and active. CONCLUSIONS: Youth who use a
      mobility device are vulnerable to health and safety risks and isolation during
      the winter, but they also display signs of resilience.

PMID- 24564362
TI  - Ancient eudicot hexaploidy meets ancestral eurosid gene order.
AB  - BACKGROUND: A hexaploidization event over 125 Mya underlies the evolutionary
      lineage of the majority of flowering plants, including very many species of
      agricultural importance. Half of these belong to the rosid subgrouping,
      containing severals whose genome sequences have been published. Although most
      duplicate and triplicate genes have been lost in all descendants, clear traces of
      the original chromosome triples can be discerned, their internal contiguity
      highly conserved in some genomes and very fragmented in others. To understand the
      particular evolutionary patterns of plant genomes, there is a need to
      systematically survey the fate of the subgenomes of polyploids, including the
      retention of a small proportion of the duplicate and triplicate genes and the
      reconstruction of putative ancestral intermediates between the original hexaploid
      and modern species, in this case the ancestor of the eurosid clade. RESULTS: We
      quantitatively trace the fate of gene triples originating in the hexaploidy
      across seven core eudicot flowering plants, and fit this to a two-stage model,
      pre- and post-radiation. We also measure the simultaneous dynamics of duplicate
      orthologous gene loss in three rosids, as influenced by biological functional
      class. We propose a new protocol for reconstructing ancestral gene order using
      only gene adjacency data from pairwise genomic analyses, based on repeating
      MAXIMUM WEIGHT MATCHING at two levels of resolution, an approach designed to
      transcend limitations on reconstructed contig size, while still avoiding the
      ambiguities of a multiplicity of solutions. Applied to three high-quality rosid
      genomes without subsequent polyploidy events, our automated procedure
      reconstructs the ancestor of the eurosid clade. CONCLUSIONS: The gene loss
      analysis and the ancestor reconstruction present complementary assessments of
      post-hexaploidization evolution, the first at the level of individual gene
      families within and across sister genomes and the second at the chromosome level.
      Despite the loss of more than 95% of gene duplicates and triplicates, and despite
      major structural rearrangement, our reconstructed eurosid ancestor clearly
      identifies the three regions corresponding to each of the seven original
      chromosomes of the earlier pre-hexaploid ancestor. Functional analysis confirmed
      trends reported for more recent plant polyploidy events: genes involved with
      regulation and responses were retained in multiple copies, while genes involved
      with metabolic processes were lost.

PMID- 24564363
TI  - The recombinant vaccinia virus gene product, B18R, neutralizes interferon alpha
      and alleviates histopathological complications in an HIV encephalitis mouse
      model.
AB  - Interferon-alpha (IFN-alpha) has been identified as a neurotoxin that plays a
      prominent role in human immunodeficiency virus (HIV)-associated neurocognitive
      disorders and HIV encephalitis (HIVE) pathology. IFN-alpha is associated with
      cognitive dysfunction in other inflammatory diseases where IFN-alpha is
      upregulated. Trials of monoclonal anti-IFN-alpha antibodies have been generally
      disappointing possibly due to high specificity to limited IFN-alpha subtypes and
      low affinity. We investigated a novel IFN-alpha inhibitor, B18R, in an
      HIVE/severe combined immunodeficiency (SCID) mouse model. Immunostaining for B18R
      in systemically treated HIVE/SCID mice suggested the ability of B18R to cross the
      blood-brain barrier (BBB). Real-time PCR indicated that B18R treatment resulted
      in a decrease in gene expression associated with IFN-alpha signaling in the
      brain. Mice treated with B18R were found to have decreased mouse mononuclear
      phagocytes and significant retention of neuronal arborization compared to
      untreated HIVE/SCID mice. Increased mononuclear phagocytes and decreased neuronal
      arborization are key features of HIVE. These results suggest that B18R crosses
      the BBB, blocks IFN-alpha signaling, and it prevents key features of HIVE
      pathology. These data suggest that the high affinity and broad IFN-alpha subtype
      specificity of B18R make it a viable alternative to monoclonal antibodies for the
      inhibition of IFN-alpha in the immune-suppressed environment. 

PMID- 24564364
TI  - Assessing the impact of human genome annotation choice on RNA-seq expression
      estimates.
AB  - BACKGROUND: Genome annotation is a crucial component of RNA-seq data analysis.
      Much effort has been devoted to producing an accurate and rational annotation of
      the human genome. An annotated genome provides a comprehensive catalogue of
      genomic functional elements. Currently, at least six human genome annotations are
      publicly available, including AceView Genes, Ensembl Genes, H-InvDB Genes, RefSeq
      Genes, UCSC Known Genes, and Vega Genes. Characteristics of these annotations
      differ because of variations in annotation strategies and information sources.
      When performing RNA-seq data analysis, researchers need to choose a genome
      annotation. However, the effect of genome annotation choice on downstream RNA-seq
      expression estimates is still unclear. This study (1) investigates the effect of
      different genome annotations on RNA-seq quantification and (2) provides
      guidelines for choosing a genome annotation based on research focus. RESULTS: We
      define the complexity of human genome annotations in terms of the number of
      genes, isoforms, and exons. This definition facilitates an investigation of
      potential relationships between complexity and variations in RNA-seq
      quantification. We apply several evaluation metrics to demonstrate the impact of
      genome annotation choice on RNA-seq expression estimates. In the mapping stage,
      the least complex genome annotation, RefSeq Genes, appears to have the highest
      percentage of uniquely mapped short sequence reads. In the quantification stage,
      RefSeq Genes results in the most stable expression estimates in terms of the
      average coefficient of variation over all genes. Stable expression estimates in
      the quantification stage translate to accurate statistics for detecting
      differentially expressed genes. We observe that RefSeq Genes produces the most
      accurate fold-change measures with respect to a ground truth of RT-qPCR gene
      expression estimates. CONCLUSIONS: Based on the observed variations in the
      mapping, quantification, and differential expression calling stages, we
      demonstrate that the selection of human genome annotation results in different
      gene expression estimates. When conducting research that emphasizes reproducible
      and robust gene expression estimates, a less complex genome annotation may be
      preferred. However, simpler genome annotations may limit opportunities for
      identifying or characterizing novel transcriptional or regulatory mechanisms.
      When conducting research that aims to be more exploratory, a more complex genome
      annotation may be preferred.

PMID- 24564365
TI  - Growth of alloy MoS(2x)Se2(1-x) nanosheets with fully tunable chemical
      compositions and optical properties.
AB  - Band gap engineering of atomically thin two-dimensional layered materials is
      critical for their applications in nanoelectronics, optoelectronics, and
      photonics. Here we report, for the first time, a simple one-step chemical vapor
      deposition approach for the simultaneous growth of alloy MoS2xSe2(1-x) triangular
      nanosheets with complete composition tunability. Both the Raman and the
      photoluminescence studies show tunable optical properties consistent with
      composition of the alloy nanosheets. Importantly, all samples show a single
      bandedge emission peak, with the spectral peak position shifting from 668 nm (for
      pure MoS2) to 795 nm (for pure MoSe2), indicating the high quality for these
      complete composition alloy nanosheets. These band gap engineered 2D structures
      could open up an exciting opportunity for probing their fundamental physical
      properties in 2D and may find diverse applications in functional
      electronic/optoelectronic devices. 

PMID- 24564366
TI  - Role of two alternate water networks in Compound I formation in P450eryF.
AB  - The P450eryF enzyme (CYP107A1) hydroxylates 6-deoxyerythronolide B to
      erythronolide B during erythromycin synthesis by Saccharopolyspora erythraea. In
      many P450 enzymes, a conserved "acid-alcohol pair" is believed to participate in
      the proton shuttling pathway for O2 activation that generates the reactive
      oxidant (Compound I, Cpd I). In CYP107A1, the alcohol-containing amino acid is
      replaced with alanine. The crystal structure of DEB bound to CYP107A1 indicates
      that one of the substrate hydroxyl groups (5-OH) may facilitate proton transfer
      during O2 activation. We applied molecular dynamics (MD) and hybrid quantum
      mechanics/molecular mechanics (QM/MM) techniques to investigate substrate
      mediated O2 activation in CYP107A1. In the QM/MM calculations, the QM region was
      treated by density functional theory, and the MM region was represented by the
      CHARMM force field. The MD simulations suggest the existence of two water
      networks around the active site, the one found in the crystal structure involving
      E360 and an alternative one involving E244. According to the QM/MM calculations,
      the first proton transfer that converts the peroxo to the hydroperoxo
      intermediate (Compound 0, Cpd 0) proceeds via the E244 water network with direct
      involvement of the 5-OH group of the substrate. For the second proton transfer
      from Cpd 0 to Cpd I, the computed barriers for the rate-limiting homolytic O-O
      cleavage are similar for the E360 and E244 pathways, and hence both glutamate
      residues may serve as proton source in this step. 

PMID- 24564367
TI  - A pilot case-cohort study of brain cancer in poultry and control workers.
AB  - We conducted an exploratory study to investigate which exposures (including
      poultry oncogenic viruses) are associated with brain cancer in poultry workers. A
      total of 46,819 workers in poultry and nonpoultry plants from the same union were
      initially followed for mortality. Brain cancer was observed to be in excess among
      poultry workers. Here we report on a pilot case-cohort study with cases
      consisting of 26 (55%) of the 47 brain cancer deaths recorded in the cohort, and
      controls consisting of a random sample of the cohort (n = 124). Exposure
      information was obtained from telephone interviews, and brain cancer mortality
      risk estimated by odds ratios. Increased risk of brain cancer was associated with
      killing chickens, odds ratio (OR) = 5.8 (95% confidence interval, 1.2-28.3);
      working in a shell-fish farm, OR = 13.0 (95% CI, 1.9-84.2); and eating uncooked
      fish, OR = 8.2 (95% CI, 1.8-37.0). Decreased risks were observed for chicken pox
      illness, OR = 0.2 (95% CI, 0.1-0.6), and measles vaccination, OR = 0.2 (95% CI,
      0.1-0.6). Killing chickens, an activity associated with the highest occupational
      exposure to poultry oncogenic viruses, was associated with brain cancer
      mortality, as were occupational and dietary shellfish exposures. These findings
      are novel. 

PMID- 24564368
TI  - Silver iodide microstructures of a uniform towerlike shape: morphology
      purification via a chemical dissolution, simultaneously boosted catalytic
      durability, and enhanced catalytic performances.
AB  - The fabrication of microstructures/nanostructures of a uniform yet well-defined
      morphology has attracted broad interest from a variety of fields of advanced
      functional materials, especially catalysts. Most of the conventional methods
      generally suffer from harsh synthesis conditions, requirement of bulky apparatus,
      or incapability of scalable production, etc. To meet these formidable challenges,
      it is strongly desired to develop a facile, cost-effective, scalable method to
      fulfill a morphology purification. By a precipitation reaction between AgNO3 and
      KI, we report that irregular AgI structures, or their mixture with towerlike AgI
      architectures could be fabricated. Compared to the former, the mixed structures
      exhibit enhanced catalytic reactivity toward the photodegradation of Methyl
      Orange pollutant. However, its catalytic durability, which is one of the most
      crucial criteria that are required by superior catalysts, is poor. We further
      show that the irregular structures could be facilely removed from the mixture via
      a KI-assisted chemical dissolution, producing AgI of a uniform towerlike
      morphology. Excitingly, after such simple morphology purification, our towerlike
      AgI displays not only a boosted catalytic durability but also an enhanced
      catalytic reactivity. Our chemical dissolution-based morphology purification
      protocol might be extended to other systems, wherein high-quality advanced
      functional materials of desired properties might be developed. 

PMID- 24564369
TI  - An efficient synthesis of novel fused cycloheptatrienes through Mn(II)-mediated
      formal intermolecular [2 + 2 + 2 + 1] cycloaddition.
AB  - A new method for manganous acetate tetrahydrate mediated formal intermolecular [2
      + 2 + 2 + 1] cycloaddition was developed for the synthesis of fused
      cycloheptatriene derivatives from N-(acylmethyl)pyridinium iodides and
      naphthoquinone. This method provides an innovative route for the efficient and
      convenient construction of fused seven-membered carbocycles from simple starting
      materials. 

PMID- 24564371
TI  - The reaction rates of O2 with closed-shell and open-shell Al(x)- and Ga(x)-
      clusters under single-collision conditions: experimental and theoretical
      investigations toward a generally valid model for the hindered reactions of O2
      with metal atom clusters.
AB  - In order to characterize the oxidation of metallic surfaces, the reactions of O2
      with a number of Al(x)(-) and, for the first time, Ga(x)(-) clusters as molecular
      models have been investigated, and the results are presented here for x = 9-14.
      The rate coefficients were determined with FT-ICR mass spectrometry under single
      collision conditions at O2 pressures of ~10(-8) mbar. In this way, the
      qualitatively known differences in the reactivities of the even- and odd-numbered
      clusters toward O2 could be quantified experimentally. To obtain information
      about the elementary steps, we additionally performed density functional theory
      calculations. The results show that for both even- and odd-numbered clusters the
      formation of the most stable dioxide species, [M(x)O2](-), proceeds via the less
      stable peroxo species, [M(x)(+)...O2(2-)](-), which contains M-O-O-M moieties. We
      conclude that the formation of these peroxo intermediates may be a reason for the
      decreased reactivity of the metal clusters toward O2. This could be one of the
      main reasons why O2 reactions with metal surfaces proceed more slowly than Cl2
      reactions with such surfaces, even though O2 reactions with both Al metal and Al
      clusters are more exothermic than are reactions of Cl2 with them. Furthermore,
      our results indicate that the spin-forbidden reactions of (3)O2 with closed-shell
      clusters and the spin-allowed reactions with open-shell clusters to give singlet
      [M(x)(+)...O2(2-)](-) are the root cause for the observed even/odd differences in
      reactivity.

PMID- 24564370
TI  - CorrelaGenes: a new tool for the interpretation of the human transcriptome.
AB  - BACKGROUND: The amount of gene expression data available in public repositories
      has grown exponentially in the last years, now requiring new data mining tools to
      transform them in information easily accessible to biologists. RESULTS: By
      exploiting expression data publicly available in the Gene Expression Omnibus
      (GEO) database, we developed a new bioinformatics tool aimed at the
      identification of genes whose expression appeared simultaneously altered in
      different experimental conditions, thus suggesting co-regulation or coordinated
      action in the same biological process. To accomplish this task, we used the 978
      human GEO Curated DataSets and we manually performed the selection of 2,109 pair
      wise comparisons based on their biological rationale. The lists of differentially
      expressed genes, obtained from the selected comparisons, were stored in a
      PostgreSQL database and used as data source for the CorrelaGenes tool. Our
      application uses a customized Association Rule Mining (ARM) algorithm to identify
      sets of genes showing expression profiles correlated with a gene of interest. The
      significance of the correlation is measured coupling the Lift, a well-known
      standard ARM index, and the chi(2) p value. The manually curated selection of the
      comparisons and the developed algorithm constitute a new approach in the field of
      gene expression profiling studies. Simulation performed on 100 randomly selected
      target genes allowed us to evaluate the efficiency of the procedure and to obtain
      preliminary data demonstrating the consistency of the results. CONCLUSIONS: The
      preliminary results of the simulation showed how CorrelaGenes could contribute to
      the characterization of molecular pathways and biological processes integrating
      data obtained from other applications and available in public repositories.

PMID- 24564372
TI  - Positive and negative expressions of shyness in toddlers: are they related to
      anxiety in the same way?
AB  - Shyness has generally been investigated as a negative and unpleasant emotional
      state, strongly related to social anxiety and loneliness. However, recent
      evidence has suggested that shyness may have a positive and socially adaptive
      form. We examined whether the positive expression of shyness differs from the
      negative expression of shyness during toddlerhood, and whether a negative
      relation to anxiety exists. Participants were 30-month-old children (N=102; 56
      girls) who were asked to mimic animal sounds with a novel person (performance)
      and then to watch their performance (self-watching). Their expression of pleasure
      (positive reactions) and distress (negative reactions), as well as their positive
      and negative expressions of shyness, were coded. Children's temperamental level
      of shyness, sociability, and anxiety were measured with parent-reported
      questionnaires. Toddlers produced more positive and negative displays of shyness
      in the performance task than in the self-watching task. Children's positive
      expression of shyness was associated with lower parent-reported anxiety and
      higher sociability. Negative reactions, but not negative shyness, were related to
      children's higher anxiety levels and lower sociability. Multiple linear
      regression analyses confirmed a negative predictive role of the positive
      expression of shyness on anxiety. These results suggest that the positive
      expression of shyness can regulate early anxiety symptoms and already serves a
      social function in interpersonal interactions in early childhood.

PMID- 24564373
TI  - The essence of innocence: consequences of dehumanizing Black children.
AB  - The social category "children" defines a group of individuals who are perceived
      to be distinct, with essential characteristics including innocence and the need
      for protection (Haslam, Rothschild, & Ernst, 2000). The present research examined
      whether Black boys are given the protections of childhood equally to their peers.
      We tested 3 hypotheses: (a) that Black boys are seen as less "childlike" than
      their White peers, (b) that the characteristics associated with childhood will be
      applied less when thinking specifically about Black boys relative to White boys,
      and (c) that these trends would be exacerbated in contexts where Black males are
      dehumanized by associating them (implicitly) with apes (Goff, Eberhardt,
      Williams, & Jackson, 2008). We expected, derivative of these 3 principal
      hypotheses, that individuals would perceive Black boys as being more responsible
      for their actions and as being more appropriate targets for police violence. We
      find support for these hypotheses across 4 studies using laboratory, field, and
      translational (mixed laboratory/field) methods. We find converging evidence that
      Black boys are seen as older and less innocent and that they prompt a less
      essential conception of childhood than do their White same-age peers. Further,
      our findings demonstrate that the Black/ape association predicted actual racial
      disparities in police violence toward children. These data represent the first
      attitude/behavior matching of its kind in a policing context. Taken together,
      this research suggests that dehumanization is a uniquely dangerous intergroup
      attitude, that intergroup perception of children is underexplored, and that both
      topics should be research priorities.

PMID- 24564374
TI  - Social exclusion and stereotyping: why and when exclusion fosters individuation
      of others.
AB  - Exclusion triggers a desire to re-capture connections with others. To facilitate
      this goal, excluded individuals typically process social information especially
      carefully. One implication of this is that exclusion may foster judgments of
      others that are reliant on a careful consideration of their idiosyncratic
      behaviors rather than on more superficial features. We predicted, therefore, that
      excluded individuals should individuate more and stereotype less than non
      excluded individuals and that such effects should be in service of identifying
      appropriate re-affiliation candidates. In 3 replications of Experiment 1,
      excluded (compared to non-excluded) individuals rendered less stereotypic
      judgments of occupational and racial group members described with mildly or
      ambiguously counter-stereotypic information. Confirming such processes aid with
      re-affiliation, Experiments 2 and 3 showed that these effects occurred for social
      targets that represented reasonable sources of re-affiliation, but not for
      offensive social targets (i.e., Skinheads) or non-social agents. Experiment 4
      underscored that excluded participants process presented social information more
      carefully (individuate), showing greater differentiation in judgments of highly
      stereotype-consistent and stereotype-inconsistent targets. Implications for the
      social exclusion literature are discussed.

PMID- 24564375
TI  - enRoute: dynamic path extraction from biological pathway maps for exploring
      heterogeneous experimental datasets.
AB  - Jointly analyzing biological pathway maps and experimental data is critical for
      understanding how biological processes work in different conditions and why
      different samples exhibit certain characteristics. This joint analysis, however,
      poses a significant challenge for visualization. Current techniques are either
      well suited to visualize large amounts of pathway node attributes, or to
      represent the topology of the pathway well, but do not accomplish both at the
      same time. To address this we introduce enRoute, a technique that enables
      analysts to specify a path of interest in a pathway, extract this path into a
      separate, linked view, and show detailed experimental data associated with the
      nodes of this extracted path right next to it. This juxtaposition of the
      extracted path and the experimental data allows analysts to simultaneously
      investigate large amounts of potentially heterogeneous data, thereby solving the
      problem of joint analysis of topology and node attributes. As this approach does
      not modify the layout of pathway maps, it is compatible with arbitrary graph
      layouts, including those of hand-crafted, image-based pathway maps. We
      demonstrate the technique in context of pathways from the KEGG and the
      Wikipathways databases. We apply experimental data from two public databases, the
      Cancer Cell Line Encyclopedia (CCLE) and The Cancer Genome Atlas (TCGA) that both
      contain a wide variety of genomic datasets for a large number of samples. In
      addition, we make use of a smaller dataset of hepatocellular carcinoma and common
      xenograft models. To verify the utility of enRoute, domain experts conducted two
      case studies where they explore data from the CCLE and the hepatocellular
      carcinoma datasets in the context of relevant pathways. 

PMID- 24564376
TI  - McKittrick-Wheelock syndrome: a rare cause of acute renal failure and hypokalemia
      not to be overlooked.
AB  - McKittrick-Wheelock syndrome is a rare disorder in which a colorectal tumor
      (usually a villous adenoma) determines secretory mucous diarrhea, which in turn
      leads to prerenal acute renal failure, hyponatremia, hypokalemia and metabolic
      acidosis. Even though the outcome is usually favorable with complete recovery
      after surgery, the diagnosis is often delayed, making the patient susceptible to
      life-threatening complications, mainly severe acidosis and hypokalemia. We
      present two paradigmatic cases with extreme electrolytes imbalance and complete
      recovery following the appropriate treatment. The pathogenesis of this
      degenerative condition is discussed in detail.

PMID- 24564377
TI  - MetaCluster-TA: taxonomic annotation for metagenomic data based on assembly
      assisted binning.
AB  - BACKGROUND: Taxonomic annotation of reads is an important problem in metagenomic
      analysis. Existing annotation tools, which rely on the approach of aligning each
      read to the taxonomic structure, are unable to annotate many reads efficiently
      and accurately as reads (~100 bp) are short and most of them come from unknown
      genomes. Previous work has suggested assembling the reads to make longer contigs
      before annotation. More reads/contigs can be annotated as a longer contig (in
      Kbp) can be aligned to a taxon even if it is from an unknown species as long as
      it contains a conserved region of that taxon. Unfortunately existing metagenomic
      assembly tools are not mature enough to produce long enough contigs. Binning
      tries to group reads/contigs of similar species together. Intuitively, reads in
      the same group (cluster) should be annotated to the same taxon and these reads
      altogether should cover a significant portion of the genome alleviating the
      problem of short contigs if the quality of binning is high. However, no existing
      work has tried to use binning results to help solve the annotation problem. This
      work explores this direction. RESULTS: In this paper, we describe MetaCluster-TA,
      an assembly-assisted binning-based annotation tool which relies on an innovative
      idea of annotating binned reads instead of aligning each read or contig to the
      taxonomic structure separately. We propose the novel concept of the 'virtual
      contig' (which can be up to 10 Kb in length) to represent a set of reads and then
      represent each cluster as a set of 'virtual contigs' (which together can be total
      up to 1 Mb in length) for annotation. MetaCluster-TA can outperform widely-used
      MEGAN4 and can annotate (1) more reads since the virtual contigs are much longer;
      (2) more accurately since each cluster of long virtual contigs contains global
      information of the sampled genome which tends to be more accurate than short
      reads or assembled contigs which contain only local information of the genome;
      and (3) more efficiently since there are much fewer long virtual contigs to align
      than short reads. MetaCluster-TA outperforms MetaCluster 5.0 as a binning tool
      since binning itself can be more sensitive and precise given long virtual contigs
      and the binning results can be improved using the reference taxonomic database.
      CONCLUSIONS: MetaCluster-TA can outperform widely-used MEGAN4 and can annotate
      more reads with higher accuracy and higher efficiency. It also outperforms
      MetaCluster 5.0 as a binning tool.

PMID- 24564378
TI  - Tuberculosis in childhood: a systematic review of national and international
      guidelines.
AB  - BACKGROUND: Paediatric tuberculosis (TB) represents a major public health concern
      worldwide. About 1 million children aged less than 15 years develop TB each year,
      contributing to 3-25% of the total TB caseload. The aim of this review is to
      evaluate national and international guidelines concerning tuberculosis in
      childhood and compare them in terms of diagnosis and treatment strategies.
      METHODS: A literature search of the Pubmed database was performed from January
      2000 to August 2013, using the terms "tuberculosis" and "children". The search
      was limited to guidelines and consensus conferences, human species and full text
      availability, with no language restrictions. RESULTS: Twenty-seven national and
      international guidelines are identified. Several discrepancies on the diagnosis
      workup of TB are underlined. The main points of disagreement are represented by
      the interpretation of tuberculin skin test (TST) result and the recommendations
      on the use of TST and/or interferon-gamma release assay (IGRA) for the diagnosis
      of TB infection. Otherwise, all guidelines are in agreement that a
      microbiological confirmation should always be sought. Similarly, susceptibility
      drug testing and genotyping should be performed whenever it is possible on the
      basis of resources availability. On the contrary, the use of nucleic acid
      amplification tests (NAATs) for the M. tuberculosis detection is still
      controversial. A general consensus exists, otherwise, on TB treatment and only
      minor discrepancies are evidenced, such as the recommendations on daily or
      intermittent treatment regimens. CONCLUSIONS: Despite advances in TB diagnostic
      tools have been reached during the last decade, a lack of uniformity in their
      availability, indication and interpretation has relevant consequences for
      clinical practice. Further studies need to be performed to clarify this issue and
      identify a reliable and reproducible diagnostic workup. Moreover, future studies
      should analyze the drug metabolism and the efficacy of intermittent dosing
      regimes in childhood, as well as new treatment regimens in order to improve the
      therapy compliance.

PMID- 24564379
TI  - Agreement between Orbscan II, VuMAX UBM and Artemis-2 very-high frequency
      ultrasound scanner for measurement of anterior chamber depth.
AB  - BACKGROUND: The aim was to compare the anterior chamber depth (ACD) measurements
      taken with Orbscan II, ultrasound biomicroscopy (UBM) and the Artemis-2 VHF (very
      high-frequency) ultrasound scanner in normal subjects. METHODS: In this
      prospective study, one eye from each of 60 normal subjects was randomly selected.
      Three subjects dropped out of the study because they were apprehensive about the
      UBM examination; their data were excluded entirely. Measurements of ACD were
      taken with the Orbscan II, UBM and Artemis-2 VHFUS. Results were obtained for
      coefficient of variance (CV) and intra-class correlation coefficient (ICC), and
      statistical analysis was by repeated-measures analysis of variance (ANOVA) for
      intra-observer repeatability. ANOVA and Bland-Altman analyses were used to
      determine limits of agreement (LOA) between the three instruments. RESULTS: The
      average ACD (+/- standard deviation) was 3.13 +/- 0.34 mm, 2.96 +/- 0.27 mm and
      2.87 +/- 0.31 mm for the Orbscan II, UBM and Artemis-2 VHFUS, respectively. The
      repeatability scores were 0.015 +/- 0.014%, 0.08 +/- 0.09% and 0.07 +/- 0.06% for
      the Orbscan II, UBM and Artemis-2 VHFUS, respectively. The ICC for repeatability
      of Orbscan II, UBM and Artemis-2 VHFUS measurements was high and equal to 0.99%.
      The intra-observer repeatability scores of the ACD measurement p-values using
      Orbscan II, UBM and Artemis-2 VHFUS were 0.12, 0.70 and 0.10, respectively. The
      mean difference and standard deviations for ACD measurements using Orbscan II vs
      UBM, Orbscan II vs Artemis-2 VHFUS and UBM vs Artemis-2 VHFUS were 0.17 +/- 0.31
      mm, 0.27 +/- 0.34 mm and 0.10 +/- 0.18 mm, respectively. LOAs were 0.78 to -0.44
      mm, 0.93 to -0.39 mm and 0.45 to -0.26 mm. ANOVA revealed a statistically
      significant difference between the Orbscan II, UBM and Artemis-2 VHFUS (p <
      0.0001). CONCLUSIONS: Measurements by the three instruments show high
      repeatability. UBM and the Artemis-2 VHFUS can be used interchangeably, but the
      Orbscan II cannot be used interchangeably with UBM or the Artemis-2 VHFUS.

PMID- 24564380
TI  - Simple re-instantiation of small databases using cloud computing.
AB  - BACKGROUND: Small bioinformatics databases, unlike institutionally funded large
      databases, are vulnerable to discontinuation and many reported in publications
      are no longer accessible. This leads to irreproducible scientific work and
      redundant effort, impeding the pace of scientific progress. RESULTS: We describe
      a Web-accessible system, available online at http://biodb100.apbionet.org, for
      archival and future on demand re-instantiation of small databases within minutes.
      Depositors can rebuild their databases by downloading a Linux live operating
      system (http://www.bioslax.com), preinstalled with bioinformatics and UNIX tools.
      The database and its dependencies can be compressed into an ".lzm" file for
      deposition. End-users can search for archived databases and activate them on
      dynamically re-instantiated BioSlax instances, run as virtual machines over the
      two popular full virtualization standard cloud-computing platforms, Xen
      Hypervisor or vSphere. The system is adaptable to increasing demand for disk
      storage or computational load and allows database developers to use the re
      instantiated databases for integration and development of new databases.
      CONCLUSIONS: Herein, we demonstrate that a relatively inexpensive solution can be
      implemented for archival of bioinformatics databases and their rapid re
      instantiation should the live databases disappear.

PMID- 24564381
TI  - ViralPhos: incorporating a recursively statistical method to predict
      phosphorylation sites on virus proteins.
AB  - BACKGROUND: The phosphorylation of virus proteins by host kinases is linked to
      viral replication. This leads to an inhibition of normal host-cell functions.
      Further elucidation of phosphorylation in virus proteins is required in order to
      aid in drug design and treatment. However, only a few studies have investigated
      substrate motifs in identifying virus phosphorylation sites. Additionally,
      existing bioinformatics tool do not consider potential host kinases that may
      initiate the phosphorylation of a virus protein. RESULTS: 329 experimentally
      verified phosphorylation fragments on 111 virus proteins were collected from
      virPTM. These were clustered into subgroups of significantly conserved motifs
      using a recursively statistical method. Two-layered Support Vector Machines
      (SVMs) were then applied to train a predictive model for the identified substrate
      motifs. The SVM models were evaluated using a five-fold cross validation which
      yields an average accuracy of 0.86 for serine, and 0.81 for threonine.
      Furthermore, the proposed method is shown to perform at par with three other
      phosphorylation site prediction tools: PPSP, KinasePhos 2.0 and GPS 2.1.
      CONCLUSION: In this study, we propose a computational method, ViralPhos, which
      aims to investigate virus substrate site motifs and identify potential
      phosphorylation sites on virus proteins. We identified informative substrate
      motifs that matched with several well-studied kinase groups as potential
      catalytic kinases for virus protein substrates. The identified substrate motifs
      were further exploited to identify potential virus phosphorylation sites. The
      proposed method is shown to be capable of predicting virus phosphorylation sites
      and has been implemented as a web server http://csb.cse.yzu.edu.tw/ViralPhos/.

PMID- 24564383
TI  - Some food for thought on nanoeducation.

PMID- 24564385
TI  - SET-induced biaryl cross-coupling: an S(RN)1 reaction.
AB  - The SET-induced biaryl cross-coupling reaction is established as the first
      example of a Grignard S(RN)1 reaction. The reaction is examined within the
      mechanistic framework of dissociative electron transfer in the presence of a
      Lewis acid. DFT calculations show that the reaction proceeds through a radical
      intermediate in the form of an Mg ion-radical cage, which eludes detection in
      trapping experiments by reacting quickly to form an MgPh2 radical anion
      intermediate. A new mechanism is proposed.

PMID- 24564382
TI  - Bivalent inhibitors of protein kinases.
AB  - Protein kinases are key players in a large number of cellular signaling pathways.
      Dysregulated kinase activity has been implicated in a number of diseases, and
      members of this enzyme family are of therapeutic interest. However, due to the
      fact that most inhibitors interact with the highly conserved ATP-binding sites of
      kinases, it is a significant challenge to develop pharmacological agents that
      target only one of the greater than 500 kinases present in humans. A potential
      solution to this problem is the development of bisubstrate and bivalent kinase
      inhibitors, in which an active site-directed moiety is tethered to another ligand
      that targets a location outside of the ATP-binding cleft. Because kinase
      signaling specificity is modulated by regions outside of the ATP-binding site,
      strategies that exploit these interactions have the potential to provide reagents
      with high target selectivity. This review highlights examples of kinase
      interaction sites that can potentially be exploited by bisubstrate and bivalent
      inhibitors. Furthermore, an overview of efforts to target these interactions with
      bisubstrate and bivalent inhibitors is provided. Finally, several examples of the
      successful application of these reagents in a cellular setting are described.

PMID- 24564386
TI  - Estimating the cost-savings associated with bundling maternal and child health
      interventions: a proposed methodology.
AB  - BACKGROUND: There is a pressing need to include cost data in the Lives Saved Tool
      (LiST). This paper proposes a method that combines data from both the WHO
      CHOosing Interventions that are Cost-Effective (CHOICE) database and the
      OneHealth Tool (OHT) to develop unit costs for delivering child and maternal
      health services, both alone and bundled. METHODS: First, a translog cost function
      is estimated to calculate factor shares of personnel, consumables, other direct
      (variable or recurrent costs excluding personnel and consumables) and indirect
      (capital or investment) costs. Primary source facility level data from Kenya,
      Namibia, South Africa, Uganda, Zambia and Zimbabwe are utilized, with separate
      analyses for hospitals and health centres. Second, the resulting other-direct and
      indirect factor shares are applied to country unit costs from the WHO CHOICE unit
      cost database to calculate those portions of unit cost. Third, the remainder of
      the costs is calculated using default data from the OHT. Fourth, we calculate the
      effect of bundling services by assuming that a LiST intervention visit takes an
      average of 20 minutes when delivered alone but only incremental time in addition
      to the basic visit when delivered in a bundle. RESULTS: Personnel costs account
      for the greatest share of costs for both hospitals and health centres at 50% and
      38%, respectively. The percentages differ between hospitals and health centres
      for consumables (21% versus 17%), other direct (7.5% versus 6.75%), and indirect
      (22% versus 23%) costs. Combining the other-direct and indirect factor shares
      with the WHO CHOICE database and the other costs from OHT provides a
      comprehensive cost estimate of LiST interventions. Finally, the cost of six
      recommended antenatal care (ANC) interventions is $69.76 when delivered alone,
      but $61.18 when delivered as a bundle, a savings of $8.58 (12.2%). CONCLUSIONS:
      This paper proposes a method for estimating a comprehensive cost of providing
      child and maternal health interventions by combining labor, consumables and drug
      costs from OHT with indirect and other-direct proportional costs from WHO CHOICE.
      In addition, we demonstrate the potential cost savings that can be achieved from
      bundling the delivery of essential antenatal care interventions rather than
      delivering the same interventions alone.

PMID- 24564387
TI  - Brief sexual histories and routine HIV/STD testing by medical providers.
AB  - Clinicians who routinely take patient sexual histories have the opportunity to
      assess patient risk for sexually transmitted diseases (STDs), including human
      immunodeficiency virus (HIV), and make appropriate recommendations for routine
      HIV/STD screenings. However, less than 40% of providers conduct sexual histories
      with patients, and many do not receive formal sexual history training in school.
      After partnering with a national professional organization of physicians, we
      trained 26 (US and US territory-based) practicing physicians (58% female; median
      age=48 years) regarding sexual history taking using both in-person and webinar
      methods. Trainings occurred during either a 6-h onsite or 2-h webinar session. We
      evaluated their post-training experiences integrating sexual histories during
      routine medical visits. We assessed use of sexual histories and routine HIV/STD
      screenings. All participating physicians reported improved sexual history taking
      and increases in documented sexual histories and routine HIV/STD screenings. Four
      themes emerged from the qualitative evaluations: (1) the need for more sexual
      history training; (2) the importance of providing a gender-neutral sexual history
      tool; (3) the existence of barriers to routine sexual histories/testing; and (4)
      unintended benefits for providers who were conducting routine sexual histories.
      These findings were used to develop a brief, gender-neutral sexual history tool
      for clinical use. This pilot evaluation demonstrates that providers were willing
      to utilize a sexual history tool in clinical practice in support of HIV/STD
      prevention efforts.

PMID- 24564388
TI  - Interdisciplinary dialogue for education, collaboration, and innovation:
      intelligent Biology and Medicine in and beyond 2013.
AB  - The 2013 International Conference on Intelligent Biology and Medicine (ICIBM
      2013) was held on August 11-13, 2013 in Nashville, Tennessee, USA. The conference
      included six scientific sessions, two tutorial sessions, one workshop, two poster
      sessions, and four keynote presentations that covered cutting-edge research
      topics in bioinformatics, systems biology, computational medicine, and
      intelligent computing. Here, we present a summary of the conference and an
      editorial report of the supplements to BMC Genomics and BMC Systems Biology that
      include 19 research papers selected from ICIBM 2013. 

PMID- 24564390
TI  - Method for preparation, programming, and characterization of miniaturized
      particulate shape-memory polymer matrices.
AB  - Their capability to change their shape on demand has created significant interest
      for shape-memory polymers (SMPs) in minimally invasive surgery. To evaluate the
      miniaturization of SMP matrices for small-sized implants or controlled release
      systems, a strategy to prepare and evaluate microsized SMP model particles is
      required. This methodological study reports the emulsion-based preparation of ~30
      MUm microparticles (MPs) from a phase-segregated SMP, poly(epsilon-caprolactone)
      [PCL] and poly(omega-pentadecalactone) [PPDL], with a particular focus on the
      effects of process parameters such as polymer solvents or stabilizer
      type/concentration on formation and size distribution of SMP MPs. Processes for
      the preparation of SMP MP-loaded water-soluble polymer films with tailored
      mechanical properties were developed and applied for programming the SMP MP to a
      temporary ellipsoid shape by film stretching. For the functional evaluation of
      shape recovery of MPs, a light microscopy-based setup with temperature control is
      proposed by which the stimuli-induced switching of the microsized SMP matrices
      could be confirmed. Overall, by applying this methodological strategy to various
      thermoplastic SMPs, a routine to identify and characterize the microscale
      functionality of SMPs in miniaturized applications will be broadly accessible.

PMID- 24564389
TI  - Sex, genetics, and the control of thyroxine and thyrotropin in mice.
AB  - BACKGROUND: Previously, we studied the genetic basis for variability in total
      thyroxine (TT4) as part of investigating induced Graves' hyperthyroidism in
      panels of genetically diverse recombinant inbred (RI) mice. Because Graves'
      disease occurs predominantly in women, we used female mice. A limitation of this
      approach is that thyrotropin (TSH) is undetectable by some assays in most female
      mice. METHOD: Variation in levels of serum TSH, TT4, and free thyroxine (FT4) was
      measured in males from three related RI families (CXB, BXH, and AXBXA) followed
      by quantitative genetic analysis and mapping of these traits. RESULTS: In
      general, TSH levels were higher in males than females. FT4 levels were also
      higher in males than in females, but TT4 sex differences were absent or
      inconsistent. Chromosomal linkage was only observed for TSH in BXH males and for
      FT4 in AXBXA males. Different chromosomes were linked to TT4 in males of the
      three RI sets. The most striking finding came from genetic linkages in males
      versus our previous data for females. TT4 was linked to the same chromosomal loci
      in CXB males and females. In contrast, TT4, FT4, and TSH were linked to different
      "sex-specific chromosomes" in AXBXA and BXH families. CONCLUSIONS: In three RI
      mouse families, TSH and FT4 were significantly higher in males than females.
      Linkage analysis revealed chromosomal overlap for TT4 in males and females for
      one RI set but striking sex differences for TT4, FT4, and TSH linkage in two RI
      sets. Our findings provide a cautionary note: genetic linkage analysis of thyroid
      hormones traits in mice should be studied separately in males and females.

PMID- 24564392
TI  - Organoselenium-catalyzed mild dehydration of aldoximes: an unexpected practical
      method for organonitrile synthesis.
AB  - Areneselenenic acids (ArSeOH), readily generated from diaryl diselenides and H2O2
      by in situ oxidation, were found to be effective and reusable catalysts for
      dehydration of aldoximes, leading to a practical and scalable preparation of
      useful organonitriles under mild conditions. 

PMID- 24564391
TI  - Transcript features alone enable accurate prediction and understanding of gene
      expression in S. cerevisiae.
AB  - BACKGROUND: Gene expression is a central process in all living organisms. Central
      questions in the field are related to the way the expression levels of genes are
      encoded in the transcripts and affect their evolution, and the potential to
      predict expression levels solely by transcript features. In this study we analyze
      S. cerevisiae, a model organism with the most abundant relevant cellular and
      genomic measurements, to evaluate the accuracy in which expression levels can be
      predicted by different parts of the transcript. To this end, we perform various
      types of regression analyses based on a total of 5323 features of the transcript.
      The main advantage of the proposed predictors over previous ones is related to
      the accurate and comprehensive definitions of the relevant transcript features,
      which are based on biophysical knowledge of the gene transcription and
      translation processes, their modeling and evolution. RESULTS: Cross validation
      analyses of our predictors demonstrate that they achieve a correlation of
      0.68/0.68/0.70/0.61/0.81 with mRNA levels, ribosomal density, protein levels,
      proteins per mRNA molecule (PPR), and ribosomal load (RL) respectively (all p
      values <10(-140)). When we consider predictors that are based exclusively on the
      features related to different parts of the transcript (5'UTR, ORF, 3'UTR), the
      correlations with protein levels were 0.27/0.71/0.25 (all p-values <10(-5)),
      suggesting that the information in the UTRs is redundant, and features of the ORF
      alone yield similar predictions to the ones obtained based on the entire
      transcript. CONCLUSIONS: The reported results demonstrate that in the analyzed
      model organism the expression levels of a gene are encoded in the transcript.
      Specifically, the prediction of a large fraction of the variance of the different
      gene expression steps based on transcript features alone is feasible in S.
      cerevisiae. We report dozens of novel transcript features related to expression
      levels predictions, demonstrating how such analyses can aid in understanding the
      gene expression process and its evolution, and how such predictors can be
      designed for other organisms in the future.

PMID- 24564394
TI  - Central adiponectin acutely improves glucose tolerance in male mice.
AB  - Adiponectin, an adipocyte-derived hormone, regulates glucose and lipid
      metabolism. It is also antiinflammatory. During obesity, adiponectin levels and
      sensitivity are reduced. Whereas the action of adiponectin in the periphery is
      well established the neuroendocrine role of adiponectin is largely unknown. To
      address this we analyzed the expression of adiponectin and the 2 adiponectin
      receptors (AdipoR1 and AdipoR2) in response to fasting and to diet-induced and
      genetic obesity. We also investigated the acute impact of adiponectin on central
      regulation of glucose homeostasis. Adiponectin (1 MUg) was injected
      intracerebroventricularly (ICV), and glucose tolerance tests were performed in
      dietary and genetic obese mice. Finally, the influence of ICV adiponectin
      administration on central signaling cascades regulating glucose homeostasis and
      on markers of hypothalamic inflammation was assessed. Gene expression of
      adiponectin was down-regulated whereas AdipoR1 was up-regulated in the arcuate
      nucleus of fasted mice. High-fat (HF) feeding increased AdipoR1 and AdipoR2 gene
      expression in this region. In mice on a HF diet and in leptin-deficient mice
      acute ICV adiponectin improved glucose tolerance 60 minutes after injection,
      whereas normoglycemia in control mice was unaffected. ICV adiponectin increased
      pAKT, decreased phospho-AMP-activated protein kinase, and did not change phospho
      signal transducer and activator of transcription 3 immunoreactivity. In HF-fed
      mice, ICV adiponectin reversed parameters of hypothalamic inflammation and
      insulin resistance as determined by the number of phospho-glycogen synthase
      kinase 3 beta(Ser9) and phospho-c-Jun N-terminal kinase (Thr183/Tyr185)
      immunoreactive cells in the arcuate nucleus and ventromedial hypothalamus. This
      study demonstrates that the insulin-sensitizing properties of adiponectin are at
      least partially based on a neuroendocrine mechanism that involves centrally
      synthesized adiponectin. 

PMID- 24564395
TI  - Programming of the hypothalamic-pituitary-adrenal axis by neonatal intermittent
      hypoxia: effects on adult male ACTH and corticosterone responses are stress
      specific.
AB  - Intermittent hypoxia (IH) is an animal model of apnea-induced hypoxia, a common
      stressor in the premature neonate. Neonatal stressors may have long-term
      programming effects in the adult. We hypothesized that neonatal exposure to IH
      leads to significant changes in basal and stress-induced hypothalamic-pituitary
      adrenal (HPA) axis function in the adult male rat. Rat pups were exposed to
      normoxia (control) or 6 approximately 30-second cycles of IH (5% or 10% inspired
      O2) daily on postnatal days 2-6. At approximately 100 days of age, we assessed
      the diurnal rhythm of plasma corticosterone and stress-induced plasma ACTH and
      corticosterone responses, as well as mRNA expression of pertinent genes within
      the HPA axis. Basal diurnal rhythm of plasma corticosterone concentrations in the
      adult rat were not affected by prior exposure to neonatal IH. Adults exposed to
      10% IH as neonates exhibited an augmented peak ACTH response and a prolonged
      corticosterone response to restraint stress; however, HPA axis responses to
      insulin-induced hypoglycemia were not augmented in adults exposed to neonatal IH.
      Pituitary Pomc, Crhr1, Nr3c1, Nr3c2, Avpr1b, and Hif1a mRNA expression was
      decreased in adults exposed to neonatal 10% IH. Expression of pertinent
      hypothalamic and adrenal mRNAs was not affected by neonatal IH. We conclude that
      exposure to neonatal 10% IH programs the adult HPA axis to hyperrespond to acute
      stimuli in a stressor-specific manner.

PMID- 24564393
TI  - Metabolic influences on reproduction: adiponectin attenuates GnRH neuronal
      activity in female mice.
AB  - Metabolic dysfunctions are often linked to reproductive abnormalities.
      Adiponectin (ADP), a peripheral hormone secreted by white adipose tissue, is
      important in energy homeostasis and appetite regulation. GnRH neurons are
      integral components of the reproductive axis, controlling synthesis, and release
      of gonadotropins. This report examined whether ADP can directly act on GnRH
      neurons. Double-label immunofluorescence on brain sections from adult female
      revealed that a subpopulation of GnRH neurons express ADP receptor (AdipoR)2.
      GnRH/AdipoR2+ cells were distributed throughout the forebrain. To determine the
      influence of ADP on GnRH neuronal activity and the signal transduction pathway of
      AdipoR2, GnRH neurons maintained in explants were assayed using whole-cell patch
      clamping and calcium imaging. This mouse model system circumvents the dispersed
      distribution of GnRH neurons within the forebrain, making analysis of large
      numbers of GnRH cells possible. Single-cell PCR analysis and immunocytochemistry
      confirmed the presence of AdipoR2 in GnRH neurons in explants. Functional
      analysis revealed 20% of the total GnRH population responded to ADP, exhibiting
      hyperpolarization or decreased calcium oscillations. Perturbation studies
      revealed that ADP activates AMP kinase via the protein kinase Czeta/liver kinase
      B1 pathway. The modulation of GnRH neuronal activity by ADP demonstrated in this
      report directly links energy balance to neurons controlling reproduction. 

PMID- 24564396
TI  - Assessment of the metabolic pathways associated with glucose-stimulated biphasic
      insulin secretion.
AB  - Biphasic glucose-stimulated insulin secretion involves a rapid first phase
      followed by a prolonged second phase of insulin secretion. The biochemical
      pathways that control these 2 phases of insulin secretion are poorly defined. In
      this study, we used a gas chromatography mass spectroscopy-based metabolomics
      approach to perform a global analysis of cellular metabolism during biphasic
      insulin secretion. A time course metabolomic analysis of the clonal beta-cell
      line 832/13 cells showed that glycolytic, tricarboxylic acid, pentose phosphate
      pathway, and several amino acids were strongly correlated to biphasic insulin
      secretion. Interestingly, first-phase insulin secretion was negatively associated
      with L-valine, trans-4-hydroxy-L-proline, trans-3-hydroxy-L-proline, DL-3
      aminoisobutyric acid, L-glutamine, sarcosine, L-lysine, and thymine and
      positively with L-glutamic acid, flavin adenine dinucleotide, caprylic acid,
      uridine 5'-monophosphate, phosphoglycerate, myristic acid, capric acid, oleic
      acid, linoleic acid, and palmitoleic acid. Tricarboxylic acid cycle intermediates
      pyruvate, alpha-ketoglutarate, and succinate were positively associated with
      second-phase insulin secretion. Other metabolites such as myo-inositol,
      cholesterol, DL-3-aminobutyric acid, and L-norleucine were negatively associated
      metabolites with the second-phase of insulin secretion. These studies provide a
      detailed analysis of key metabolites that are either negatively or positively
      associated with biphasic insulin secretion. The insights provided by these data
      set create a framework for planning future studies in the assessment of the
      metabolic regulation of biphasic insulin secretion.

PMID- 24564397
TI  - Intraperitoneal CCK and fourth-intraventricular Apo AIV require both peripheral
      and NTS CCK1R to reduce food intake in male rats.
AB  - Apolipoprotein AIV (Apo AIV) and cholecystokinin (CCK) are secreted in response
      to fat consumption, and both cause satiation via CCK 1 receptor (CCK-1R)
      containing vagal afferent nerves to the nucleus of the solitary tract (NTS),
      where Apo AIV is also synthesized. Fasted male Long-Evans rats received ip CCK-8
      or fourth-ventricular (i4vt) Apo AIV alone or in combination. Food intake and c
      Fos proteins (a product of the c-Fos immediate-early gene) were assessed. i4vt
      Apo AIV and/or ip CCK at effective doses reduced food intake and activated c-Fos
      proteins in the NTS and hypothalamic arcuate nucleus and paraventricular nucleus.
      Blockade of the CCK-1R by i4vt lorglumide adjacent to the NTS attenuated the
      satiating and c-Fos-stimulating effects of CCK and Apo AIV, alone or in
      combination. Maintenance on a high-fat diet (HFD) for 10 weeks resulted in weight
      gain and attenuation of both the behavioral and c-Fos responses to a greater
      extent than occurred in low-fat diet-fed and pair-fed HFD animals. These
      observations suggest that NTS Apo AIV or/and peripheral CCK requires vagal CCK-1R
      signaling to elicit satiation and that maintenance on a HFD reduces the satiating
      capacity of these 2 signals. 

PMID- 24564399
TI  - In utero exposure to the endocrine disruptor di-(2-ethylhexyl) phthalate induces
      long-term changes in gene expression in the adult male adrenal gland.
AB  - The plasticizer di-(2-ethylhexyl) phthalate (DEHP) is used to add flexibility to
      polyvinylchloride polymers and as a component of numerous consumer and medical
      products. DEHP and its metabolites have been detected in amniotic fluid and
      umbilical cord blood, suggesting fetal exposure. In the present study, we used an
      in utero exposure model in which pregnant rat dams were exposed to 1- to 300-mg
      DEHP/kg.d from gestational day 14 until birth. We previously reported that this
      window of exposure to environmentally relevant doses of DEHP resulted in reduced
      levels of serum testosterone and aldosterone in adult male offspring and that the
      effects on aldosterone were sustained in elderly rats and resulted in decreased
      blood pressure. Here, we characterized the long-term effects of in utero DEHP
      exposure by performing global gene expression analysis of prepubertal (postnatal
      d 21) and adult (postnatal d 60) adrenal glands. We found that the peroxisome
      proliferator-activated receptor and lipid metabolism pathways were affected by
      DEHP exposure. Expression of 2 other DEHP targets, hormone-sensitive lipase and
      phosphoenolpyruvate carboxykinase 1 (Pck1), correlated with reduced aldosterone
      levels and may account for the inhibitory effect of DEHP on adrenal steroid
      formation. The angiotensin II and potassium pathways were up-regulated in
      response to DEHP. In addition, the potassium intermediate/small conductance
      calcium-activated channel Kcnn2 and 2-pore-domain potassium channel Knck5 were
      identified as DEHP targets. Based on this gene expression analysis, we measured
      fatty acid-binding protein 4 and phosphoenolpyruvate carboxykinase 1 in sera from
      control and DEHP-exposed rats and identified both proteins as putative serum
      biomarkers of in utero DEHP exposure. These results shed light on molecular
      targets that mediate DEHP long-term effects and, in doing so, provide means by
      which to assess past DEHP exposure. 

PMID- 24564398
TI  - Fibroblast growth factor 21 and thyroid hormone show mutual regulatory dependency
      but have independent actions in vivo.
AB  - Thyroid hormone (TH) regulates fibroblast growth factor 21 (FGF21) levels in the
      liver and in the adipose tissue. In contrast, peripheral FGF21 administration
      leads to decreased circulating levels of TH. These data suggest that FGF21 and TH
      could interact to regulate metabolism. In the present study, we confirmed that TH
      regulates adipose and hepatic FGF21 expression and serum levels in mice. We next
      investigated the influence of TH administration on key serum metabolites, gene
      expression in the liver and brown adipose tissue, and energy expenditure in FGF21
      knockout mice. Surprisingly, we did not observe any significant differences in
      the effects of TH on FGF21 knockout mice compared with those in wild-type
      animals, indicating that TH acts independently of FGF21 for the specific outcomes
      studied. Furthermore, exogenous FGF21 administration to hypothyroid mice led to
      similar changes in serum and liver lipid metabolites and gene expression in both
      hypothyroid and euthyroid mice. Thus, it appears that FGF21 and TH have similar
      actions to decrease serum and liver lipids despite having some divergent
      regulatory effects. Whereas TH leads to up-regulation in the liver and down
      regulation in brown adipose tissue of genes involved in the lipid synthesis
      pathway (eg, fatty acid synthase (FASN) and SPOT14), FGF21 leads to the opposite
      changes in expression of these genes. In conclusion, TH and FGF21 act
      independently on the outcomes studied, despite their ability to regulate each
      other's circulating levels. Thus, TH and FGF21 may modulate the availability of
      each other in critical metabolic states. 

PMID- 24564400
TI  - Conditional overexpression of liver receptor homolog-1 in female mouse mammary
      epithelium results in altered mammary morphogenesis via the induction of TGF
      beta.
AB  - Liver receptor homolog-1 (LRH-1) is an orphan nuclear receptor that belongs to
      the NR5A subgroup of nuclear receptors. LRH-1 induces key genes to regulate
      metabolic process, ovarian function, cancer cell proliferation, and
      steroidogenesis. In the breast, LRH-1 modulates and synergizes with endogenous
      estrogen signaling to promote breast cancer cell proliferation. We used small
      interfering RNA knockdown strategies to deplete LRH-1 in breast cancer cells and
      followed with microarray analysis to identify LRH-1-dependent mechanisms. We
      identified key genes involved in TGF-beta signaling to be highly responsive to
      LRH-1 knockdown. This relationship was validated in 2 breast cancer cell lines
      overexpressing LRH-1 in vitro and in a novel transgenic mouse with targeted LRH-1
      overexpression in mammary epithelial cells. Notably, TGF-beta signaling was
      activated in LRH-1-overexpressing breast cancer cells and mouse mammary glands.
      Further analyses of mammary gross morphology revealed a significant reduction in
      mammary lateral budding after LRH-1 overexpression. These findings suggest that
      the altered mammary morphogenesis in LRH-1 transgenic animals is mediated via
      enhanced TGF-beta expression. The regulation of TGF-beta isoforms and SMAD2/3
      mediated downstream signaling by LRH-1 also implicates a potential contribution
      of LRH-1 in breast cancer. Collectively, these data demonstrate that LRH-1
      regulates TGF-beta expression and downstream signaling in mouse mammary glands. 

PMID- 24564401
TI  - Are physical activity levels linked to nutrient adequacy? Implications for cancer
      risk.
AB  - Cancer prevention guidelines recommend a healthy body mass index, physical
      activity, and nutrient intake from food rather than supplements. Sedentary
      individuals may restrict energy intake to prevent weight gain and in so doing may
      compromise nutritional intake. We conducted a cross-sectional analysis to
      determine if adequacy of micronutrients is linked to physical activity levels
      (PALs) in healthy-weight adults. Tomorrow Project participants in Alberta, Canada
      (n = 5333), completed past-year diet and physical activity questionnaires. The
      percent meeting Dietary Reference Intakes (DRIs) was reported across low and high
      PAL groups, and the relation between PAL and percent achieved DRI was determined
      using multiple linear regression analyses. Overall, <50% of healthy-weight
      participants met DRIs for folate, calcium, and vitamin D. Percent achieved DRI
      increased linearly with increasing PAL in both genders (P < 0.01). A hypothetical
      increase in PAL from 1.4 to 1.9 was associated with a DRI that was 8%-13% higher
      for folate and vitamin C (men) and 5%-15% higher for calcium and iron (women).
      Healthy-weight adults at higher PALs appear more likely to meet DRIs for
      potential cancer-preventing nutrients. The benefits of higher PALs may extend
      beyond the usual benefits attributed to physical activity to include having a
      more favorable impact on nutrient adequacy. 

PMID- 24564402
TI  - Cost-effectiveness of asenapine in the treatment of schizophrenia in Canada.
AB  - OBJECTIVE: Asenapine is the first tetracyclic antipsychotic approved in Canada
      for the treatment of schizophrenia (SCZ). Asenapine has shown a comparable
      efficacy profile to other atypical antipsychotics and it is associated with a
      favourable metabolic profile and less weight gain. This study aimed to assess the
      economic impact of asenapine compared to other atypical antipsychotics in the
      treatment of SCZ in Canada. METHODS: A decision tree combined with a Markov model
      was constructed to assess the cost-utility of asenapine compared with other
      atypical antipsychotics. The decision tree takes into account the occurrence of
      extrapyramidal symptoms, the probability of switching to a different
      antipsychotic, and the probability of gaining weight. The Markov model takes into
      account long-term metabolic complications including diabetes, hypertension,
      coronary heart diseases, and stroke. In the base-case analysis, asenapine was
      compared to olanzapine. Asenapine was also compared with other atypical
      antipsychotics commonly used in Canada in alternative scenarios. Analyses were
      conducted from both Canadian Ministry of Health (MoH) and societal perspectives
      over a 5-year time horizon. RESULTS: In the treatment of SCZ, asenapine is a
      dominant strategy over olanzapine from both MoH and societal perspectives.
      Compared to quetiapine, asenapine is also a dominant strategy. Furthermore,
      asenapine has a favorable economic impact compared to ziprasidone and
      aripiprazole, as these antipsychotics are not cost-effective compared to
      asenapine from both MoH and societal perspectives. CONCLUSION: Despite the short
      time horizon, the lack of compliance data and the assumptions made, this economic
      evaluation demonstrates that asenapine is a cost-effective strategy compared to
      olanzapine and to most of the atypical antipsychotics frequently used in Canada.

PMID- 24564403
TI  - Literature classification for semi-automated updating of biological
      knowledgebases.
AB  - BACKGROUND: As the output of biological assays increase in resolution and volume,
      the body of specialized biological data, such as functional annotations of gene
      and protein sequences, enables extraction of higher-level knowledge needed for
      practical application in bioinformatics. Whereas common types of biological data,
      such as sequence data, are extensively stored in biological databases, functional
      annotations, such as immunological epitopes, are found primarily in semi
      structured formats or free text embedded in primary scientific literature.
      RESULTS: We defined and applied a machine learning approach for literature
      classification to support updating of TANTIGEN, a knowledgebase of tumor T-cell
      antigens. Abstracts from PubMed were downloaded and classified as either
      "relevant" or "irrelevant" for database update. Training and five-fold cross
      validation of a k-NN classifier on 310 abstracts yielded classification accuracy
      of 0.95, thus showing significant value in support of data extraction from the
      literature. CONCLUSION: We here propose a conceptual framework for semi-automated
      extraction of epitope data embedded in scientific literature using principles
      from text mining and machine learning. The addition of such data will aid in the
      transition of biological databases to knowledgebases.

PMID- 24564405
TI  - Potential public health hazards, exposures and health effects from unconventional
      natural gas development.
AB  - The rapid increase in unconventional natural gas (UNG) development in the United
      States during the past decade has brought wells and related infrastructure closer
      to population centers. This review evaluates risks to public health from chemical
      and nonchemical stressors associated with UNG, describes likely exposure pathways
      and potential health effects, and identifies major uncertainties to address with
      future research. The most important occupational stressors include mortality,
      exposure to hazardous materials and increased risk of industrial accidents. For
      communities near development and production sites the major stressors are air
      pollutants, ground and surface water contamination, truck traffic and noise
      pollution, accidents and malfunctions, and psychosocial stress associated with
      community change. Despite broad public concern, no comprehensive population-based
      studies of the public health effects of UNG operations exist. Major uncertainties
      are the unknown frequency and duration of human exposure, future extent of
      development, potential emission control and mitigation strategies, and a paucity
      of baseline data to enable substantive before and after comparisons for affected
      populations and environmental media. Overall, the current literature suggests
      that research needs to address these uncertainties before we can reasonably
      quantify the likelihood of occurrence or magnitude of adverse health effects
      associated with UNG production in workers and communities. 

PMID- 24564404
TI  - Reducing bias in RNA sequencing data: a novel approach to compute counts.
AB  - BACKGROUND: In the last decade, Next-Generation Sequencing technologies have been
      extensively applied to quantitative transcriptomics, making RNA sequencing a
      valuable alternative to microarrays for measuring and comparing gene
      transcription levels. Although several methods have been proposed to provide an
      unbiased estimate of transcript abundances through data normalization, all of
      them are based on an initial count of the total number of reads mapping on each
      transcript. This procedure, in principle robust to random noise, is actually
      error-prone if reads are not uniformly distributed along sequences, as happens
      indeed due to sequencing errors and ambiguity in read mapping. Here we propose a
      new approach, called maxcounts, to quantify the expression assigned to an exon as
      the maximum of its per-base counts, and we assess its performance in comparison
      with the standard approach described above, which considers the total number of
      reads aligned to an exon. The two measures are compared using multiple data sets
      and considering several evaluation criteria: independence from gene-specific
      covariates, such as exon length and GC-content, accuracy and precision in the
      quantification of true concentrations and robustness of measurements to
      variations of alignments quality. RESULTS: Both measures show high accuracy and
      low dependency on GC-content. However, maxcounts expression quantification is
      less biased towards long exons with respect to the standard approach. Moreover,
      it shows lower technical variability at low expressions and is more robust to
      variations in the quality of alignments. CONCLUSIONS: In summary, we confirm that
      counts computed with the standard approach depend on the length of the feature
      they are summarized on, and are sensitive to the non-uniform distribution of
      reads along transcripts. On the opposite, maxcounts are robust to biases due to
      the non-uniformity distribution of reads and are characterized by a lower
      technical variability. Hence, we propose maxcounts as an alternative approach for
      quantitative RNA-sequencing applications.

PMID- 24564406
TI  - Association of T869, C509T, G915C gene polymorphism of transforming growth factor
      beta1 with IgA nephropathy risk.
AB  - This meta-analysis was conducted to assess the association of transforming growth
      factor-beta1 (TGF-beta1) T869C, C509T, G915C gene polymorphism with the risk of
      IgA nephropathy (IgAN). The association literatures were identified from PubMed,
      Cochrane Library up to October 1, 2013, and eligible reports were recruited and
      synthesized. Five reports were recruited into this meta-analysis for the
      association of TGF-beta1 T869C, C509T, G915C gene polymorphism with IgAN risk. In
      this meta-analysis, the association of TGF-beta1 T869C, C509T, G915C gene
      polymorphism with IgAN risk was not found. In conclusion, TGF-beta1 T869C, C509T,
      G915C gene polymorphism is not associated with the IgAN risk. However, more
      studies should be performed in the future to confirm this association.

PMID- 24564408
TI  - Cu(I)-catalyzed regio- and stereoselective [6 + 3] cycloaddition of azomethine
      ylides with tropone: an efficient asymmetric access to bridged
      azabicyclo[4.3.1]decadienes.
AB  - An unprecedented Cu(I)-catalyzed asymmetric [6 + 3] cycloaddition of tropone with
      azomethine ylides was reported, which performs well over a broad scope of
      substrates and offers a unique and facile access to the synthetically useful
      bridged azabicyclo[4.3.1]decadiene derivatives in good yields with high levels of
      diastereoselectivities and enantioselectivities under mild conditions. 

PMID- 24564407
TI  - Application of microRNA and mRNA expression profiling on prognostic biomarker
      discovery for hepatocellular carcinoma.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most highly malignant
      and lethal cancers of the world. Its pathogenesis has been reported to be multi
      factorial, and the molecular carcinogenesis of HCC can not be attributed to just
      a few individual genes. Based on the microRNA and mRNA expression profiling of
      normal liver tissues, pericancerous hepatocellular tissues and hepatocellular
      carcinoma tissues, we attempted to find prognosis related gene sets for HCC
      patients. RESULTS: We identified differentially expressed genes (DEG) from three
      comparisons: Cancer/Normal, Cancer/Pericancerous and Pericancerous/Normal. GSEA
      (gene set enrichment analysis) were performed. Based on the enriched gene sets of
      GO terms, pathways and transcription factor targets, it was found that the genome
      instability and cell proliferation increased while the metabolism and
      differentiation decreased in HCC tissues. The expression profile of DEGs in each
      enriched gene set was used to correlate to the postoperative survival time of HCC
      patients. Nine gene sets were found to prognostic correlation. Furthermore, after
      substituting DEG-targeting-microRNA for DEG members of each gene set, two gene
      sets with the microRNA expression profiles were obtained that had prognostic
      potential. CONCLUSIONS: The malignancy of HCC could be represented by gene sets,
      and pericancerous liver exhibits important characteristics of liver cancer. The
      expression level of gene sets not only in HCC but also in the pericancerous liver
      showed potential for prognosis implying an option for HCC prognosis at an early
      stage. Additionally, the gene-targeting-microRNA expression profiles also showed
      prognostic potential, demonstrating that the multi-factorial molecular
      pathogenesis of HCC is contributed by various genes and microRNAs.

PMID- 24564409
TI  - Visual cavity analysis in molecular simulations.
AB  - Molecular surfaces provide a useful mean for analyzing interactions between
      biomolecules; such as identification and characterization of ligand binding sites
      to a host macromolecule. We present a novel technique, which extracts potential
      binding sites, represented by cavities, and characterize them by 3D graphs and by
      amino acids. The binding sites are extracted using an implicit function sampling
      and graph algorithms. We propose an advanced cavity exploration technique based
      on the graph parameters and associated amino acids. Additionally, we
      interactively visualize the graphs in the context of the molecular surface. We
      apply our method to the analysis of MD simulations of Proteinase 3, where we
      verify the previously described cavities and suggest a new potential cavity to be
      studied. 

PMID- 24564411
TI  - Neural networks learn highly selective representations in order to overcome the
      superposition catastrophe.
AB  - A key insight from 50 years of neurophysiology is that some neurons in cortex
      respond to information in a highly selective manner. Why is this? We argue that
      selective representations support the coactivation of multiple "things" (e.g.,
      words, objects, faces) in short-term memory, whereas nonselective codes are often
      unsuitable for this purpose. That is, the coactivation of nonselective codes
      often results in a blend pattern that is ambiguous; the so-called superposition
      catastrophe. We show that a recurrent parallel distributed processing network
      trained to code for multiple words at the same time over the same set of units
      learns localist letter and word codes, and the number of localist codes scales
      with the level of the superposition. Given that many cortical systems are
      required to coactivate multiple things in short-term memory, we suggest that the
      superposition constraint plays a role in explaining the existence of selective
      codes in cortex.

PMID- 24564410
TI  - Structural analysis on mutation residues and interfacial water molecules for
      human TIM disease understanding.
AB  - BACKGROUND: Human triosephosphate isomerase (HsTIM) deficiency is a genetic
      disease caused often by the pathogenic mutation E104D. This mutation, located at
      the side of an abnormally large cluster of water in the inter-subunit interface,
      reduces the thermostability of the enzyme. Why and how these water molecules are
      directly related to the excessive thermolability of the mutant have not been
      investigated in structural biology. RESULTS: This work compares the structure of
      the E104D mutant with its wild type counterparts. It is found that the water
      topology in the dimer interface of HsTIM is atypical, having a "wet-core-dry-rim"
      distribution with 16 water molecules tightly packed in a small deep region
      surrounded by 22 residues including GLU104. These water molecules are co
      conserved with their surrounding residues in non-archaeal TIMs (dimers) but not
      conserved across archaeal TIMs (tetramers), indicating their importance in
      preserving the overall quaternary structure. As the structural permutation
      induced by the mutation is not significant, we hypothesize that the excessive
      thermolability of the E104D mutant is attributed to the easy propagation of
      atoms' flexibility from the surface into the core via the large cluster of water.
      It is indeed found that the B factor increment in the wet region is higher than
      other regions, and, more importantly, the B factor increment in the wet region is
      maintained in the deeply buried core. Molecular dynamics simulations revealed
      that for the mutant structure at normal temperature, a clear increase of the root
      mean-square deviation is observed for the wet region contacting with the large
      cluster of interfacial water. Such increase is not observed for other interfacial
      regions or the whole protein. This clearly suggests that, in the E104D mutant,
      the large water cluster is responsible for the subunit interface flexibility and
      overall thermolability, and it ultimately leads to the deficiency of this enzyme.
      CONCLUSIONS: Our study reveals that a large cluster of water buried in protein
      interfaces is fragile and high-maintenance, closely related to the structure,
      function and evolution of the whole protein.

PMID- 24564412
TI  - Maternal-infant relationship quality and risk of obesity at age 5.5 years in a
      national US cohort.
AB  - BACKGROUND: Poor quality relationships between mothers and toddlers have been
      associated with higher risk for childhood obesity, but few prospective studies of
      obesity have assessed maternal-child relationship quality in infancy. In addition
      it is not known whether the increased risk is associated with the mother's or the
      child's contribution to the relationship quality. METHODS: We analyzed data (n =
      5650) from the Early Childhood Longitudinal Study, Birth Cohort, a national study
      of U.S. children born in 2001 and followed until they entered kindergarten. At 9
      months of age, the Nursing Child Assessment Teaching Scale (NCATS) was used to
      assess the quality of observed playtime interactions between mothers and infants,
      yielding separate scores for maternal and infant behaviors. Obesity (BMI >=95th
      percentile) at age 5.5 years was based on measured weight and height. RESULTS:
      The prevalence (95% confidence interval) of obesity at 5.5 years of age was
      higher among children in the lowest quartile of maternal NCATS score (20.2% [95%
      CI: 17.2%, 23.2%]) than in the highest quartile (13.9% [11.3%, 16.5%]), but
      maternal NCATS score was not significantly associated with obesity after
      adjustment for race/ethnicity, maternal education and household income. The
      prevalence of obesity at 5.5 years of age was similar among children in the
      lowest quartile of infant NCATS score (17.4% [14.4%, 20.3%]) and in the highest
      quartile (17.6% 14.4%, 20.8%]), and was not changed with covariate adjustment.
      CONCLUSIONS: Maternal-infant relationship quality, assessed by direct observation
      at 9 months of age in a national sample, was not associated with an increased
      risk of obesity at age 5.5 years after controlling for sociodemographic
      characteristics.

PMID- 24564413
TI  - Associations between Grawe's general mechanisms of change and Young's early
      maladaptive schemas in psychotherapy research: a comparative study of change
      processes.
AB  - OBJECTIVE: The study aimed at analyzing associations between Grawe's general
      mechanisms of change and Young's early maladaptive schemas (EMS). METHOD:
      Therefore, 98 patients completed the Scale for the Multiperspective Assessment of
      General Change Mechanisms in Psychotherapy (SACiP), the Young Shema Questionnaire
      Short Form Revised (YSQ S3R), and diverse outcome measures at the beginning and
      end of treatment. RESULTS: Our results are important for clinical applications,
      as we demonstrated strong predictive effects of change mechanisms on schema
      domains using regression analyses and cross-lagged panel models. CONCLUSIONS:
      Resource activation experiences seem to be especially crucial in fostering
      alterations in EMS, as this change mechanism demonstrated significant
      associations with several schema domains. Future research should investigate
      these aspects in more detail using observer-based micro-process analyses.

PMID- 24564415
TI  - Environmental estrogen exposure during fetal life: a time bomb for prostate
      cancer.

PMID- 24564416
TI  - Prolactin and energy homeostasis: pathophysiological mechanisms and therapeutic
      considerations.

PMID- 24564418
TI  - Quantitative evaluation of interaction force between functional groups in protein
      and polymer brush surfaces.
AB  - To understand interactions between polymer surfaces and different functional
      groups in proteins, interaction forces were quantitatively evaluated by force
      versus-distance curve measurements using atomic force microscopy with a
      functional-group-functionalized cantilever. Various polymer brush surfaces were
      systematically prepared by surface-initiated atom transfer radical polymerization
      as well-defined model surfaces to understand protein adsorption behavior. The
      polymer brush layers consisted of phosphorylcholine groups
      (zwitterionic/hydrophilic), trimethylammonium groups (cationic/hydrophilic),
      sulfonate groups (anionic/hydrophilic), hydroxyl groups (nonionic/hydrophilic),
      and n-butyl groups (nonionic/hydrophobic) in their side chains. The interaction
      forces between these polymer brush surfaces and different functional groups
      (carboxyl groups, amino groups, and methyl groups, which are typical functional
      groups existing in proteins) were quantitatively evaluated by force-versus
      distance curve measurements using atomic force microscopy with a functional-group
      functionalized cantilever. Furthermore, the amount of adsorbed protein on the
      polymer brush surfaces was quantified by surface plasmon resonance using albumin
      with a negative net charge and lysozyme with a positive net charge under
      physiological conditions. The amount of proteins adsorbed on the polymer brush
      surfaces corresponded to the interaction forces generated between the functional
      groups on the cantilever and the polymer brush surfaces. The weakest interaction
      force and least amount of protein adsorbed were observed in the case of the
      polymer brush surface with phosphorylcholine groups in the side chain. On the
      other hand, positive and negative surfaces generated strong forces against the
      oppositely charged functional groups. In addition, they showed significant
      adsorption with albumin and lysozyme, respectively. These results indicated that
      the interaction force at the functional group level might be a suitable parameter
      for understanding protein adsorption. 

PMID- 24564414
TI  - Old dog, new trick: a direct role for leptin in regulating microbiota
      composition.

PMID- 24564420
TI  - sigma-Aromaticity in hexa-group 16 atom-substituted benzene dications: a
      theoretical study.
AB  - C6I6(2+) has been reported to have a sigma-aromatic character since removal of
      two sigma anti-bonding electrons localized on iodines results in fulfilling
      Huckel (4n+2) rules for I6(2+) as well as C6 parts. To search for molecules
      possessing similar character, hexa-group 16 atom-substituted benzene dications
      C6(ChH)6(2+) (Ch = S, Se, Te) and their derivatives are examined for aromatic
      character by using nucleus-independent chemical shift (NICS). For these
      dications, in which iodines in C6I6(2+) are replaced by group 16 atoms, negative
      NICS values larger in magnitude than for benzene are found when a sigma anti
      bonding orbital localized on group 16 atoms is unoccupied. To clarify the origin
      of large negative NICS values, they are decomposed into individual molecular
      orbitals. It has been shown that both pi bonding orbitals on C6 and sigma bonding
      orbitals on Se6 or Te6 contribute to the negative NICS values, indicating that
      the aromaticity of these dications have a substantial sigma character as well as
      pi characters. Aromaticity of group 14 and 15 atom-substituted benzene dications
      is also discussed. 

PMID- 24564421
TI  - Genome-wide probabilistic reconciliation analysis across vertebrates.
AB  - Gene duplication is considered to be a major driving force in evolution that
      enables the genome of a species to acquire new functions. A reconciliation--a
      mapping of gene tree vertices to the edges or vertices of a species tree-
      explains where gene duplications have occurred on the species tree. In this
      study, we sample reconciliations from a posterior over reconciliations, gene
      trees, edge lengths and other parameters, given a species tree and gene
      sequences. We employ a Bayesian analysis tool, based on the probabilistic model
      DLRS that integrates gene duplication, gene loss and sequence evolution under a
      relaxed molecular clock for substitution rates, to obtain this posterior.

PMID- 24564419
TI  - Clinical peculiarities of tuberculosis.
AB  - The ongoing spread of tuberculosis (TB) in poor resource countries and the
      recently increasing incidence in high resource countries lead to the need of
      updated knowledge for clinicians, particularly for pediatricians. The purpose of
      this article is to provide an overview on the most important peculiarities of TB
      in children. Children are less contagious than adults, but the risk of
      progression to active disease is higher in infants and children as compared to
      the subsequent ages. Diagnosis of TB in children is more difficult than in
      adults, because few signs are associated with primary infection, interferon-gamma
      release assays and tuberculin skin test are less reliable in younger children, M.
      tuberculosis is more rarely detected in gastric aspirates than in smears in
      adults and radiological findings are often not specific. Treatment of latent TB
      is always necessary in young children, whereas it is recommended in older
      children, as well as in adults, only in particular conditions. Antimycobacterial
      drugs are generally better tolerated in children as compared to adults, but off
      label use of second-line antimycobacterial drugs is increasing, because of
      spreading of multidrug resistant TB worldwide. Given that TB is a disease which
      often involves more than one member in a family, a closer collaboration is needed
      between pediatricians and clinicians who take care of adults. 

PMID- 24564424
TI  - Catalytic tandem C-C bond formation/cleavage of cyclopropene for allylzincation
      of aldehydes or aldimine using organozinc reagents.
AB  - The tandem allylation of aldehydes or an aldimine with allylzinc intermediates
      derived from organozinc reagents and cyclopropenes is described. The present
      three-component reaction involves carbozincation of cyclopropene and sequential
      cleavage of a cyclopropylzinc intermediate in situ without a transition-metal
      catalyst. The allylzinc intermediates generated in situ, which is an alpha,beta
      unsaturated acylanion equivalent, gave the corresponding homoallylic alcohols or
      amine in good yields. 

PMID- 24564423
TI  - A catalytic enantiotopic-group-selective Suzuki reaction for the construction of
      chiral organoboronates.
AB  - Catalytic enantiotopic-group-selective cross-couplings of achiral geminal
      bis(pinacolboronates) provide a route for the construction of nonracemic chiral
      organoboronates. In the presence of a chiral monodentate taddol-derived
      phosphoramidite ligand, these reactions occur with high levels of asymmetric
      induction. Mechanistic experiments with chiral (10)B-enriched geminal
      bis(boronates) suggest that the reaction occurs by a stereochemistry-determining
      transmetalation that occurs with inversion of configuration at carbon. 

PMID- 24564422
TI  - Handedness- and hemisphere-related differences in small-world brain networks: a
      diffusion tensor imaging tractography study.
AB  - Previous behavioral and scanning studies have suggested that handedness is
      associated with differences in brain morphology as well as in anatomical and
      functional lateralization. However, little is known about the topological
      organization of the white matter (WM) structural networks related to handedness.
      We employed diffusion tensor imaging tractography to investigate handedness- and
      hemisphere-related differences in the topological organization of the human
      cortical anatomical network. After constructing left hemispheric/right
      hemispheric weighted structural networks in 32 right-handed and 24 left-handed
      healthy individuals, we analyzed the networks by graph theoretic analysis. We
      found that both the right and left hemispheric WM structural networks in the two
      groups possessed small-world attributes (high local clustering and short paths
      between nodes), findings which are consistent with recent results from whole
      brain structural networks. In addition, the right hemisphere tended to be more
      efficient than the left hemisphere, suggesting a high efficiency of general
      information processing in the right hemisphere. Finally, we found that the right
      handed subjects had significant asymmetries in small-world properties (normalized
      clustering coefficient gamma, normalized path length lambda, and small-worldness
      sigma), while left-handed subjects had fewer asymmetries. Our findings from large
      scale brain networks aid in understanding the structural substrates underlying
      handedness-related and hemisphere-related differences in cognition and behavior.

PMID- 24564426
TI  - Sclerouveitis associated with Rosai-Dorfman disease in an HIV-infected patient.
AB  - PURPOSE: To describe a case of Rosai-Dorfman-associated sclerouveitis in an HIV
      infected patient. DESIGN: Case report. METHODS: A 49-year-old man with HIV had
      bilateral eye pain, redness, photophobia, and multiple systemic complaints. He
      underwent serial ocular examinations, abdomen/pelvis CT scan, and lymph node
      biopsy. RESULTS: Ophthalmologic evaluation revealed bilateral, nongranulomatous
      anterior uveitis and anterior scleritis. Biopsy of a retroperitoneal lymph node
      identified on CT revealed mixed inflammatory infiltrate composed of histiocytes,
      lymphocytes, and plasma cells involving fibroadipose tissue, indicating Rosai
      Dorfman disease. CONCLUSIONS: This is the first report of sclerouveitis in Rosai
      Dorfman disease. Rosai-Dorfman is typically self-limiting, occurring rarely in
      HIV.

PMID- 24564425
TI  - Mechanistic insights into mode of action of novel natural cathepsin L inhibitors.
AB  - BACKGROUND: Development of a cancerous cell takes place when it ceases to respond
      to growth-inhibiting signals and multiplies uncontrollably and can detach and
      move to other parts of the body; the process called as metastasis. A particular
      set of cysteine proteases are very active during cancer metastasis, Cathepsins
      being one of them. They are involved in tumor growth and malignancy and have also
      been reported to be overexpressed in tumor cell lines. In the present study, a
      combinatorial approach comprising three-dimensional quantitative structure
      activity relationship (3D QSAR), ligand-based pharmacophore modelling and search
      followed by cathepsin L structure-based high throughput screening was carried out
      using an initial set of 28 congeneric thiosemicarbazone derivatives as cathepsin
      L inhibitors. A 3D QSAR was derived using the alignment of a common
      thiosemicarbazone substructure. Essential structural features responsible for
      biological activity were taken into account for development of a pharmacophore
      model based on 29 congeneric thiosemicarbazone derivatives. This model was used
      to carry out an exhaustive search on a large dataset of natural compounds. A
      further cathepsin L structure-based screen identified two top scoring compounds
      as potent anti-cancer leads. RESULTS: The generated 3D QSAR model showed
      statistically significant results with an r(2) value of 0.8267, cross-validated
      correlation coefficient q(2) of 0.7232, and a pred_r(2) (r(2) value for test set)
      of 0.7460. Apart from these, a high F test value of 30.2078 suggested low
      probability of the model's failure. The pharmacophoric hypothesis chosen for
      searching the natural compound libraries was identified as DDHRR, where two Ds
      denote 2 hydrogen donors, H represents a hydrophobic group and two Rs represent
      aromatic rings, all of which are essential for the biological activity. We report
      two potential drug leads ZINC08764437 (NFP) and ZINC03846634 (APQ) obtained after
      a combined approach of pharmacophore-based search and structure-based virtual
      screen. These two compounds displayed extra precision docking scores of -7.972908
      and -7.575686 respectively suggesting considerable binding affinity for cathepsin
      L. High activity values of 5.72 and 5.75 predicted using the 3D QSAR model
      further substantiated the inhibitory potential of these identified leads.
      CONCLUSION: The present study attempts to correlate the structural features of
      thiosemicarbazone group with their biological activity by development of a robust
      3D QSAR model. Being statistically valid, this model provides near accurate
      values of the activities predicted for the congeneric set on which it is based.
      These predicted activities are good for the test set compounds making it indeed a
      statistically sound 3D QSAR model. The identified pharmacophore model DDHRR.8
      comprised of all the essential features required to interact with the catalytic
      triad of cathepsin L. A search for natural compounds based on this pharmacophore
      followed by docking studies further screened out two top scoring candidates: NFP
      and AFQ. The high binding affinity and presence of essential structural features
      in these two compounds make them ideal for consideration as natural anti-tumoral
      agents. Activity prediction using 3D QSAR model further validated their potential
      as worthy drug candidates against cathepsin L for treatment of cancer.

PMID- 24564427
TI  - PLW: Probabilistic Local Walks for detecting protein complexes from protein
      interaction networks.
AB  - BACKGROUND: Many biological processes are carried out by proteins interacting
      with each other in the form of protein complexes. However, large-scale detection
      of protein complexes has remained constrained by experimental limitations. As
      such, computational detection of protein complexes by applying clustering
      algorithms on the abundantly available protein-protein interaction (PPI) networks
      is an important alternative. However, many current algorithms have overlooked the
      importance of selecting seeds for expansion into clusters without excluding
      important proteins and including many noisy ones, while ensuring a high degree of
      functional homogeneity amongst the proteins detected for the complexes. RESULTS:
      We designed a novel method called Probabilistic Local Walks (PLW) which clusters
      regions in a PPI network with high functional similarity to find protein complex
      cores with high precision and efficiency in O (|V| log |V| + |E|) time. A seed
      selection strategy, which prioritises seeds with dense neighbourhoods, was
      devised. We defined a topological measure, called common neighbour similarity, to
      estimate the functional similarity of two proteins given the number of their
      common neighbours. CONCLUSIONS: Our proposed PLW algorithm achieved the highest F
      measure (recall and precision) when compared to 11 state-of-the-art methods on
      yeast protein interaction data, with an improvement of 16.7% over the next
      highest score. Our experiments also demonstrated that our seed selection strategy
      is able to increase algorithm precision when applied to three previous protein
      complex mining techniques. AVAILABILITY: The software, datasets and predicted
      complexes are available at http://wonglkd.github.io/PLW.

PMID- 24564428
TI  - Systematic review of strategies to increase use of oral rehydration solution at
      the household level.
AB  - BACKGROUND: Diarrhea is one of the major causes of death in children under five
      years of age, disproportionately affecting children in low- and middle-income
      countries. Treatment of diarrhea with oral rehydration solution addresses
      dehydration and reduces diarrhea related deaths. The World Health Organization
      Programme for the Control of Diarrhoeal Disease began in 1978 and while global
      ORS access rates have improved substantially over the past forty years, rates of
      ORS use have stagnated. Investigation is required to understand which
      interventions are effective in promoting the use of ORS, and where there are gaps
      in the literature. METHODS: We conducted a systematic search of peer-reviewed and
      grey literature and included interventions to promote the use of ORS for the
      treatment of acute diarrhea in children under 6 years. We used a standardized
      grading format based on the Child Health Epidemiology Research Group guidelines
      and performed meta-analysis for all categories with more than one data point.
      RESULTS: We identified 19 studies for abstraction. For co-promotion of zinc and
      ORS, mothers in the intervention group were 1.82 (95% CI 1.17, 2.85) times more
      likely to use ORS to treat their child's diarrhea episode than mothers in the
      comparison group. Meta-analysis of ORS social marketing and mass media strategies
      indicates that mothers exposed to messages were 2.05 (95% CI, 0.78, 5.42) times
      more likely to use ORS to treat their child's diarrhea episode than unexposed
      mothers. However, this is not statistically significant. Both meta-analysis had
      significant heterogeneity and were graded as moderate/low and low quality,
      respectively. CONCLUSIONS: We found few studies of interventions to promote the
      use of ORS; many categories of interventions had only one study. While there are
      some promising results, this analysis reinforces the need for further
      investigation into approaches to increasing ORS use.

PMID- 24564430
TI  - Acute phencyclidine treatment induces extensive and distinct protein
      phosphorylation in rat frontal cortex.
AB  - Phencyclidine (PCP), a noncompetitive N-methyl-D-aspartate receptor antagonist,
      induces psychotomimetic effects in humans and animals. Administration of PCP to
      rodents is used as a preclinical model for schizophrenia; however, the molecular
      mechanisms underlying the symptoms remain largely unknown. Acute PCP treatment
      rapidly induces behavioral and cognitive deficits; therefore, post-translational
      regulation of protein activity is expected to play a role at early time points.
      We performed mass-spectrometry-driven quantitative analysis of rat frontal cortex
      15, 30, or 240 min after the administration of PCP (10 mg/kg). We identified and
      quantified 23,548 peptides, including 4749 phosphopeptides, corresponding to 2604
      proteins. A total of 352 proteins exhibited altered phosphorylation levels,
      indicating that protein phosphorylation is involved in the acute response to PCP.
      Computational assessment of the regulated proteins biological function revealed
      that PCP perturbs key processes in the frontal cortex including calcium
      homeostasis, organization of cytoskeleton, endo/exocytosis, and energy
      metabolism. This study on acute PCP treatment provides the largest proteomics and
      phosphoproteomics data sets to date of a preclinical model of schizophrenia. Our
      findings contribute to the understanding of alterations in glutamatergic
      neurotransmission in schizophrenia and provide a foundation for discovery of
      novel targets for pharmacological intervention.

PMID- 24564429
TI  - Selective ligand behaviors provide new insights into agonist activation of
      nicotinic acetylcholine receptors.
AB  - Nicotinic acetylcholine receptors are a diverse set of ion channels that are
      essential to everyday brain function. Contemporary research studies selective
      activation of individual subtypes of receptors, with the hope of increasing our
      understanding of behavioral responses and neurodegenerative diseases. Here, we
      aim to expand current binding models to help explain the specificity seen among
      three activators of alpha4beta2 receptors: sazetidine-A, cytisine, and NS9283.
      Through mutational analysis, we can interchange the activation profiles of the
      stoichiometry-selective compounds sazetidine-A and cytisine. In addition,
      mutations render NS9283--currently identified as a positive allosteric modulator-
      into an agonist. These results lead to two conclusions: (1) occupation at each
      primary face of an alpha subunit is needed to activate the channel and (2) the
      complementary face of the adjacent subunit dictates the binding ability of the
      agonist.

PMID- 24564431
TI  - Pathological patterns of primary nephrotic syndrome in Central China: a
      retrospective study of 627 cases.
AB  - BACKGROUND: The pathological patterns underlying PNS in adult are poorly studied
      in Central China. METHODS: This is a retrospective analysis of the clinical and
      pathologic data involving 627 adult patients with PNS who have been finished the
      renal biopsies from January 2009 to September 2012 in XiangYa 2nd Hospital of
      Central South University. Patients enrolled in our study were all from Central
      China. RESULTS: There were 379 males and 248 females, formed the ratio of 1.53:1.
      There existed three main sorts of pathological patterns underlying PNS:
      membranous nephropathy (MN) 26.63%, minimal change disease (MCD) 23.60%, IgA
      nephropathy (IgAN) 23.39%. Among all biopsies, the proportion of FSGS underlying
      PNS increased from 5.8% during the period from 2009 to 2010 to 14.7% during the
      period from 2011 to 2012. The most common complication of PNS was infectious
      diseases, and MCD underlying PNS ran a higher risk of encountering acute renal
      injury. IgAN had the highest incidence of hematuresis. The common pathological
      patterns of PNS differed in age-brackets: IgAN and MCD were the main pathological
      lesions in patients aged from 16 to 30 years; MN mostly occurs in patients over
      30. MCD was the dominating pathological lesions underlying IgAN which expressed
      as PNS. CONCLUSIONS: (1) MN was the most frequent pathological pattern underlying
      PNS, the proportion of FSGS underlying PNS increased during the last 2 years. (2)
      The common pathological patterns of PNS differed in age-brackets and pathological
      patterns correlated to the complications or comorbidities of PNS to some extent.

PMID- 24564432
TI  - Semen quality in middle-aged males: associations with prostate-specific antigen
      and age-related prostate conditions.
AB  - OBJECTIVE: To compare markers of semen quality and related reproductive
      indicators in middle-aged males in relation to serum prostate-specific antigen
      (PSA) levels. METHODS: A total of 384 voluntary middle-aged men who underwent
      screening for prostate health were recruited. Reproductive function, semen
      quality, hormonal parameters, prostate-related pathologies, and PSA levels were
      measured. RESULTS: Total sperm count and sperm concentration were decreased in
      men with elevated serum PSA compared with age-matched controls. Serum FSH levels
      differed significantly in subjects with non-malignant, pre-malignant, and
      malignant prostate conditions. PSA levels in men with three normal semen
      variables (semen volume >= 1.5 mL, sperm density >= 15 * 10(6)/mL, and A + B
      motility >= 40%) were significantly lower compared with subjects with altered
      parameters (1.51 ng/ml vs. 2.47 ng/ml, respectively, p = 0.002). PSA showed a
      negative correlation with semen volume and total sperm count, and a positive
      correlation with semen interleukin-6. CONCLUSIONS: Our data demonstrate that
      serum PSA levels are related to impaired reproductive parameters in middle-aged
      subjects. While there is no consensus about the potential link between male
      factor infertility, impaired reproductive indicators, and prostate pathologies,
      this topic needs additional research focusing on the interactions between male
      aging, reproductive function, and the prostate.

PMID- 24564433
TI  - Predication drives verb cortical signatures.
AB  - Verbs and nouns are fundamental units of language, but their neural instantiation
      remains poorly understood. Neuropsychological research has shown that nouns and
      verbs can be damaged independently of each other, and neuroimaging research has
      found that several brain regions respond differentially to the two word classes.
      However, the semantic-lexical properties of verbs and nouns that drive these
      effects remain unknown. Here we show that the most likely candidate is
      predication: a core lexical feature involved in binding constituent arguments
      (boy, candies) into a unified syntactic-semantic structure expressing a
      proposition (the boy likes the candies). We used functional neuroimaging to test
      whether the intrinsic "predication-building" function of verbs is what drives the
      verb-noun distinction in the brain. We first identified verb-preferring regions
      with a localizer experiment including verbs and nouns. Then, we examined whether
      these regions are sensitive to transitivity--an index measuring its tendency to
      select for a direct object. Transitivity is a verb-specific property lying at the
      core of its predication function. Neural activity in the left posterior middle
      temporal and inferior frontal gyri correlates with transitivity, indicating
      sensitivity to predication. This represents the first evidence that grammatical
      class preference in the brain is driven by a word's function to build predication
      structures.

PMID- 24564435
TI  - Double C(sp3)-H bond functionalization mediated by sequential hydride
      shift/cyclization process: diastereoselective construction of polyheterocycles.
AB  - Described herein are two novel types of double C(sp(3))-H bond functionalizations
      triggered by a sequential hydride shift/cyclization process: (1) construction of
      a bicyclo[3.2.2]nonane skeleton by a [1,6]- and [1,5]-hydride shift sequence and
      (2) sequential [1,4]- and [1,5]-hydride shift mediated construction of a linear
      tricyclic skeleton. 

PMID- 24564434
TI  - Exploring cavity dynamics in biomolecular systems.
AB  - BACKGROUND: The internal cavities of proteins are dynamic structures and their
      dynamics may be associated with conformational changes which are required for the
      functioning of the protein. In order to study the dynamics of these internal
      protein cavities, appropriate tools are required that allow rapid identification
      of the cavities as well as assessment of their time-dependent structures.
      RESULTS: In this paper, we present such a tool and give results that illustrate
      the applicability for the analysis of molecular dynamics trajectories. Our
      algorithm consists of a pre-processing step where the structure of the cavity is
      computed from the Voronoi diagram of the van der Waals spheres based on
      coordinate sets from the molecular dynamics trajectory. The pre-processing step
      is followed by an interactive stage, where the user can compute, select and
      visualize the dynamic cavities. Importantly, the tool we discuss here allows the
      user to analyze the time-dependent changes of the components of the cavity
      structure. An overview of the cavity dynamics is derived by rendering the dynamic
      cavities in a single image that gives the cavity surface colored according to its
      time-dependent dynamics. CONCLUSION: The Voronoi-based approach used here enables
      the user to perform accurate computations of the geometry of the internal
      cavities in biomolecules. For the first time, it is possible to compute dynamic
      molecular paths that have a user-defined minimum constriction size. To illustrate
      the usefulness of the tool for understanding protein dynamics, we probe the
      dynamic structure of internal cavities in the bacteriorhodopsin proton pump.

PMID- 24564436
TI  - Sequence alignment by passing messages.
AB  - BACKGROUND: Sequence alignment has become an indispensable tool in modern
      molecular biology research, and probabilistic sequence alignment models have been
      shown to provide an effective framework for building accurate sequence alignment
      tools. One such example is the pair hidden Markov model (pair-HMM), which has
      been especially popular in comparative sequence analysis for several reasons,
      including their effectiveness in modeling and detecting sequence homology, model
      simplicity, and the existence of efficient algorithms for applying the model to
      sequence alignment problems. However, despite these advantages, pair-HMMs also
      have a number of practical limitations that may degrade their alignment
      performance or render them unsuitable for certain alignment tasks. RESULTS: In
      this work, we propose a novel scheme for comparing and aligning biological
      sequences that can effectively address the shortcomings of the traditional pair
      HMMs. The proposed scheme is based on a simple message-passing approach, where
      messages are exchanged between neighboring symbol pairs that may be potentially
      aligned in the optimal sequence alignment. The message-passing process yields
      probabilistic symbol alignment confidence scores, which may be used for
      predicting the optimal alignment that maximizes the expected number of correctly
      aligned symbol pairs. CONCLUSIONS: Extensive performance evaluation on protein
      alignment benchmark datasets shows that the proposed message-passing scheme
      clearly outperforms the traditional pair-HMM-based approach, in terms of both
      alignment accuracy and computational efficiency. Furthermore, the proposed scheme
      is numerically robust and amenable to massive parallelization.

PMID- 24564437
TI  - HCS-Neurons: identifying phenotypic changes in multi-neuron images upon drug
      treatments of high-content screening.
AB  - BACKGROUND: High-content screening (HCS) has become a powerful tool for drug
      discovery. However, the discovery of drugs targeting neurons is still hampered by
      the inability to accurately identify and quantify the phenotypic changes of
      multiple neurons in a single image (named multi-neuron image) of a high-content
      screen. Therefore, it is desirable to develop an automated image analysis method
      for analyzing multi-neuron images. RESULTS: We propose an automated analysis
      method with novel descriptors of neuromorphology features for analyzing HCS-based
      multi-neuron images, called HCS-neurons. To observe multiple phenotypic changes
      of neurons, we propose two kinds of descriptors which are neuron feature
      descriptor (NFD) of 13 neuromorphology features, e.g., neurite length, and
      generic feature descriptors (GFDs), e.g., Haralick texture. HCS-neurons can 1)
      automatically extract all quantitative phenotype features in both NFD and GFDs,
      2) identify statistically significant phenotypic changes upon drug treatments
      using ANOVA and regression analysis, and 3) generate an accurate classifier to
      group neurons treated by different drug concentrations using support vector
      machine and an intelligent feature selection method. To evaluate HCS-neurons, we
      treated P19 neurons with nocodazole (a microtubule depolymerizing drug which has
      been shown to impair neurite development) at six concentrations ranging from 0 to
      1000 ng/mL. The experimental results show that all the 13 features of NFD have
      statistically significant difference with respect to changes in various levels of
      nocodazole drug concentrations (NDC) and the phenotypic changes of neurites were
      consistent to the known effect of nocodazole in promoting neurite retraction.
      Three identified features, total neurite length, average neurite length, and
      average neurite area were able to achieve an independent test accuracy of 90.28%
      for the six-dosage classification problem. This NFD module and neuron image
      datasets are provided as a freely downloadable MatLab project at
      http://iclab.life.nctu.edu.tw/HCS-Neurons. CONCLUSIONS: Few automatic methods
      focus on analyzing multi-neuron images collected from HCS used in drug discovery.
      We provided an automatic HCS-based method for generating accurate classifiers to
      classify neurons based on their phenotypic changes upon drug treatments. The
      proposed HCS-neurons method is helpful in identifying and classifying chemical or
      biological molecules that alter the morphology of a group of neurons in HCS.

PMID- 24564438
TI  - Overview of the Lives Saved Tool (LiST).
AB  - This paper provides an overview of the historical development and current status
      of the Lives Saved Tool (LiST). The paper provides a general explanation of the
      modeling approach used in the model with links to web sites and other articles
      with more details. It also details the development process in developing both the
      model structure as well as the assumptions used in the model. The paper provides
      information about how LiST has been and is currently being used by various
      organizations and within national health programs. We also provide a review of
      the work that has been done to try to validate the outputs of the model. 

PMID- 24564440
TI  - Distress, support, and relationship satisfaction during military-induced
      separations: a longitudinal study among spouses of Dutch deployed military
      personnel.
AB  - The aim of this study was to examine (a) how life stress, work-family conflict,
      social support, psychological distress, and relationship satisfaction develop
      over the course of military-induced separations; (b) what best predicts
      relationship satisfaction after being separated for several months; and (c)
      whether the effects were mediated by spousal interaction. Longitudinal data were
      collected among 153 spouses of Dutch military personnel before, during, and after
      military-induced separations. Analyses demonstrated a significant decrease in
      relationship satisfaction, psychological distress, and social support over time.
      Controlling for predeployment levels of relationship satisfaction, work-family
      conflict, social support, psychological distress, and spousal interaction made
      significant contributions to the explanation of relationship satisfaction after
      military-induced separations. However, the effects on relationships varied for
      each stage of the work-related spousal separation. Hence, clinical implications
      for psychological service delivery suggested by these findings are impacted by
      the stage of the work-related spousal separation. Specifically, before the
      separation, services might focus upon balancing work and family demands; during
      the separation, services that facilitate building networks are important; and
      finally, communication remains the key service focus upon reunion.

PMID- 24564439
TI  - Project home: a pilot evaluation of an emotion-focused intervention for mothers
      reuniting with children after prison.
AB  - Nearly 2 million children in the United States have a parent in prison. The
      circumstances related to this situation place them at increased risk for
      behavioral and emotional disorders. The process of reunification between mother
      and child after release is a stressful and emotional one. A pilot study was
      conducted to develop and test a new program, Emotions: Taking Care of Yourself
      and Your Child When You Go Home. The objective of the Emotions Program was to
      teach emotion regulation and emotion coaching skills to incarcerated mothers so
      as to assist mothers and their children to cope better with the stress associated
      with incarceration and the transition home from prison. Pilot participants (N =
      47) had previously participated in Parenting Inside Out, an evidence-based
      parenting program for incarcerated parents. The participants were then assigned
      to the Emotions Program (n = 29) or the comparison condition of no additional
      treatment (n = 18). All mothers were assessed before (T1) and after the program
      (T2), and again 6 months after release from prison (T3). Intervention effects of
      the Emotions Program on mothers' emotion regulation, emotion socialization, and
      adjustment were examined using repeated-measures analysis of variance with a
      between-subjects factor of group (Emotions Program vs. comparison) and a within
      subjects factor of time (T1 vs. T2 vs. T3). Moderate time by group interaction
      effects were observed for aspects of emotion regulation, emotion socialization
      behavior, and criminal behavior in mothers, with participants in the Emotions
      condition showing improvement relative to those in the comparison condition.

PMID- 24564441
TI  - Promoting parenting to support reintegrating military families: after deployment,
      adaptive parenting tools.
AB  - The high operational tempo of the current conflicts and the unprecedented
      reliance on National Guard and Reserve forces highlights the need for services to
      promote reintegration efforts for those transitioning back to civilian family
      life. Despite evidence that parenting has significant influence on children's
      functioning, and that parenting may be impaired during stressful family
      transitions, there is a dearth of empirically supported psychological
      interventions tailored for military families reintegrating after deployment. This
      article reports on the modification of an empirically supported parenting
      intervention for families in which a parent has deployed to war. A theoretical
      rationale for addressing parenting during reintegration after deployment is
      discussed. We describe the intervention, After Deployment, Adaptive Parenting
      Tools (ADAPT), and report early feasibility and acceptability data from a
      randomized controlled effectiveness trial of ADAPT, a 14-week group-based, Web
      enhanced parenting training program. Among the first 42 families assigned to the
      intervention group, participation rates were high, and equal among mothers and
      fathers. Satisfaction was high across all 14 sessions. Implications for
      psychological services to military families dealing with the deployment process
      are discussed.

PMID- 24564442
TI  - The roles of individual and organizational factors in burnout among community
      based mental health service providers.
AB  - Public-sector mental health care providers are at high risk for burnout, which
      negatively affects not only provider well-being but also the quality of services
      for clients and the functioning of organizations. This study examines the
      influence of demographics, work characteristic, and organizational variables on
      levels of burnout among child and adolescent mental health service providers
      operating within a public-sector mental health service system. Additionally,
      given the dearth of research examining differences in burnout levels among mental
      health subdisciplines (e.g., social work, psychology, marital and family therapy)
      and mental health programs (e.g., outpatient, day treatment, wraparound, case
      management), analyses were conducted to compare levels of burnout among multiple
      mental health disciplines and program types. Surveys were completed by 285
      providers across 49 mental health programs in a large urban public mental health
      system. Variables representing dimensions of organizational climate and
      transformational leadership accounted for the greatest amount of variance in
      provider reported burnout. Analyses demonstrated significantly lower levels of
      depersonalization among wraparound providers compared to traditional case
      managers. Age was the only demographic variable related to burnout. Additionally,
      no significant effects were found for provider discipline or for agency tenure
      and caseload size. Results suggest the need to consider organizational
      development strategies aimed at creating more functional and less stressful
      climates and increasing levels of transformational leadership behaviors in order
      to reduce levels of burnout among clinicians working in public mental health
      settings for youth and families.

PMID- 24564444
TI  - Secondary trauma and ethical obligations for military psychologists: preserving
      compassion and competence in the crucible of combat.
AB  - Current ethical guidelines require psychologists to self-assess competence and
      take steps to limit or discontinue clinical work when they can no longer render
      competent care. Yet even in the best of circumstances, human beings-
      psychologists included--are not very good at evaluating their own performance.
      Moreover, when psychologists are deployed to combat zones and work constantly
      with severely traumatized and injured service members, evidence suggests that
      they become vulnerable to compassion fatigue and secondary trauma syndromes. In
      this article, we consider the unique threats to competence faced by military
      clinical psychologists. We conclude with several specific recommendations for
      deployed military clinical psychologists themselves and for the community leaders
      tasked with training and supervising them.

PMID- 24564443
TI  - Burnout in Veterans Health Administration mental health providers in
      posttraumatic stress clinics.
AB  - The purpose of this study was to conduct the first assessment of burnout among
      Veterans Health Administration (VHA) mental health clinicians providing evidence
      based posttraumatic stress disorder (PTSD) care. This study consisted of 138
      participants and the sample was mostly female (67%), Caucasian (non-Hispanic;
      81%), and married (70%) with a mean age of 44.3 years (SD = 11.2). Recruitment
      was directed through VHA PTSD Clinical Teams (PCT) throughout the United States
      based on a nationwide mailing list of PCT Clinic Directors. Participants
      completed an electronic survey that assessed demographics, organizational work
      factors, absenteeism, and burnout (assessed through the Maslach Burnout Inventory
      General Survey, MBI-GS). Twelve percent of the sample reported low Professional
      Efficacy, 50% reported high levels of Exhaustion, and 47% reported high levels of
      Cynicism as determined by the MBI-GS cut-off scores. Only workplace
      characteristics were significantly associated with provider scores on all 3
      scales. Exhaustion and Cynicism were most impacted by perceptions of
      organizational politics/bureaucracy, increased clinical workload, and control
      over how work is done. Organizational factors were also significantly associated
      with provider absenteeism and intent to leave his or her job. Findings suggest
      that providers in VHA specialty PTSD-care settings may benefit from programs or
      supports aimed at preventing and/or ameliorating burnout.

PMID- 24564445
TI  - Burnout syndrome in psychotherapists: a comparative analysis of five nations.
AB  - Burnout is a common phenomenon among psychotherapists. The purpose of this study
      was to test the Counselor Burnout Inventory (CBI; Lee et al., 2007) measurement
      invariance, as well as compare means of five latent variables (i.e., CBI
      subscales of Exhaustion, Incompetence, Negative Work Environment, Devaluing
      Client, and Deterioration in Personal Life) across five nations (United States,
      Korea, Japan, Philippines, and Hong Kong) using structural equation modeling. The
      results indicated that the assumptions of configural, factor loading, and
      intercept invariance were satisfied across the five nations. When comparing means
      of five latent variables, the results indicated differential burnout tendencies
      across the five nations. Implications for psychotherapists' burnout prevention
      and future research are discussed.

PMID- 24564446
TI  - AnnotateGenomicRegions: a web application.
AB  - BACKGROUND: Modern genomic technologies produce large amounts of data that can be
      mapped to specific regions in the genome. Among the first steps in interpreting
      the results is annotation of genomic regions with known features such as genes,
      promoters, CpG islands etc. Several tools have been published to perform this
      task. However, using these tools often requires a significant amount of
      bioinformatics skills and/or downloading and installing dedicated software.
      RESULTS: Here we present AnnotateGenomicRegions, a web application that accepts
      genomic regions as input and outputs a selection of overlapping and/or
      neighboring genome annotations. Supported organisms include human (hg18, hg19),
      mouse (mm8, mm9, mm10), zebrafish (danRer7), and Saccharomyces cerevisiae
      (sacCer2, sacCer3). AnnotateGenomicRegions is accessible online on a public
      server or can be installed locally. Some frequently used annotations and genomes
      are embedded in the application while custom annotations may be added by the
      user. CONCLUSIONS: The increasing spread of genomic technologies generates the
      need for a simple-to-use annotation tool for genomic regions that can be used by
      biologists and bioinformaticians alike. AnnotateGenomicRegions meets this demand.
      AnnotateGenomicRegions is an open-source web application that can be installed on
      any personal computer or institute server. AnnotateGenomicRegions is available
      at: http://cru.genomics.iit.it/AnnotateGenomicRegions.

PMID- 24564447
TI  - Role of asphaltenes in stabilizing thin liquid emulsion films.
AB  - Drainage kinetics, thickness, and stability of water-in-oil thin liquid emulsion
      films obtained from asphaltenes, heavy oil (bitumen), and deasphalted heavy oil
      (maltenes) diluted in toluene are studied. The results show that asphaltenes
      stabilize thin organic liquid films at much lower concentrations than maltenes
      and bitumen. The drainage of thin organic liquid films containing asphaltenes is
      significantly slower than the drainage of the films containing maltenes and
      bitumen. The films stabilized by asphaltenes are much thicker (40-90 nm) than
      those stabilized by maltenes (~10 nm). Such significant variation in the film
      properties points to different stabilization mechanisms of thin organic liquid
      films. Apparent aging effects, including gradual increase of film thickness,
      rigidity of oil/water interface, and formation of submicrometer size aggregates,
      were observed for thin organic liquid films containing asphaltenes. No aging
      effects were observed for films containing maltenes and bitumen in toluene. The
      increasing stability and lower drainage dynamics of asphaltene-containing thin
      liquid films are attributed to specific ability of asphaltenes to self-assemble
      and form 3D network in the film. The characteristic length of stable films is
      well beyond the size of single asphaltene molecules, nanoaggregates, or even
      clusters of nanoaggregates reported in the literature. Buildup of such 3D
      structure modifies the rheological properties of the liquid film to be non
      Newtonian with yield stress (gel like). Formation of such network structure
      appears to be responsible for the slower drainage of thin asphaltenes in toluene
      liquid films. The yield stress of liquid film as small as ~10(-2) Pa is
      sufficient to stop the drainage before the film reaches the critical thickness at
      which film rupture occurs. 

PMID- 24564448
TI  - Women's health in India: the role of body mass index.
AB  - We examined the health status of women in relation to their body mass indices and
      waist-to-hip ratio (WHR) by analyzing data from a follow-up study of 325 women,
      selected from the Indian National Family Health Survey (NFHS-2/1998-99) Delhi
      samples, reinterviewed after 4 years (2003). Obese women were five times more
      likely (OR = 4.87; p <.0001) and women with a higher WHR (> 0.90) were two times
      more likely (OR = 1.70; p =.050) to perceive their health condition as worse than
      others. Arthritis, hypertension, and shortness of breath were found to be higher
      among obese women and women with a high WHR. Healthy lifestyle choices must be
      promoted to contain the growing burden of obesity-related health problems among
      Indian women.

PMID- 24564449
TI  - Evaluation of read count based RNAseq analysis methods.
AB  - BACKGROUND: RNAseq technology is replacing microarray technology as the tool of
      choice for gene expression profiling. While providing much richer data than
      microarray, analysis of RNAseq data has been much more challenging. To date,
      there has not been a consensus on the best approach for conducting robust RNAseq
      analysis. RESULTS: In this study, we designed a thorough experiment to evaluate
      six read count-based RNAseq analysis methods (DESeq, DEGseq, edgeR, NBPSeq, TSPM
      and baySeq) using both real and simulated data. We found the six methods produce
      similar fold changes and reasonable overlapping of differentially expressed genes
      based on p-values. However, all six methods suffer from over-sensitivity.
      CONCLUSIONS: Based on the evaluation of runtime using real data and area under
      the receiver operating characteristic curve (AUC-ROC) using simulated data, we
      found that edgeR achieves a better balance between speed and accuracy than the
      other methods.

PMID- 24564450
TI  - New metabolites of C-glycosidic ellagitannin from Japanese oak sapwood.
AB  - Two unusual ellagitannin metabolites, quercusnins A (3) and B (4), have been
      isolated from the sapwood of Quercus crispula, and their structures determined by
      spectroscopic methods, as well as DFT calculations of (1)H and (13)C NMR chemical
      shifts of the possible four diastereomers. Treatment of the major ellagitannin
      species, vescalagin, with Shiitake mushroom (Lentinula edodes) gave 3, which
      indicated that these unique ellagitannins were the fungal metabolites of
      ellagitannins. 

PMID- 24564451
TI  - Effect of community based interventions on childhood diarrhea and pneumonia:
      uptake of treatment modalities and impact on mortality.
AB  - INTRODUCTION: Diarrhea and pneumonia are the two leading causes of mortality in
      children under five. Improvements have occurred over the past two decades but the
      progress is slow to meet the MDG-4. METHODS: We conducted a systematic review of
      the randomized controlled trials, quasi-experimental and observational studies to
      estimate the effect of community based interventions including community case
      management on the coverage of various commodities and on mortality due to
      diarrhea and pneumonia. We used a standardized abstraction and grading format and
      performed meta-analyses for all the relevant outcomes. The estimated effect of
      community based interventions was determined by applying the standard Child
      Health Epidemiology Reference Group (CHERG) rules. RESULTS: We included twenty
      four studies in this review. Community based interventions led to significant
      rise in care seeking behaviors with 13% and 9% increase in care seeking for
      pneumonia and diarrhea respectively. These interventions were associated with
      160% increase in the use of ORS and 80% increase in the use of zinc for diarrhea.
      There was a 75% decline in the unnecessary use of antibiotics for diarrhea and a
      40% decrease in treatment failure rates for pneumonia. Community case management
      for diarrhea and pneumonia is associated with a 32% reduction in pneumonia
      specific mortality, while the evidence on diarrhea related mortality is weak.
      CONCLUSION: Community based interventions have the potential to scale up care
      seeking and the use of essential commodities and significantly decrease morbidity
      and mortality burden due to diarrhea and pneumonia in children under the age of
      five years.

PMID- 24564454
TI  - Rotational spectroscopic studies of C-H . . . F interactions in the vinyl
      fluoride . . . difluoromethane complex.
AB  - Rotational spectra of the normal isotopic species and three (13)C isotopologues
      of the 1:1 complex between vinyl fluoride (CH2 ? CHF) and difluoromethane (CH2F2)
      have been measured using 480 MHz bandwidth chirped-pulse Fourier-transform
      microwave spectroscopy in the 6.5-20 GHz region. A structure for this dimer has
      been determined by fitting the moments of inertia of all isotopologues and
      confirmed by calculation of Kraitchman single isotopic substitution coordinates.
      The structure is consistent with that determined by ab initio geometry
      optimization at the MP2/6-311++G(2d,2p) level and has the difluoromethane subunit
      located on the CHF side of the vinyl fluoride subunit with three C-H . . . F
      contacts and with the hydrogen atoms of the CH2F2 straddling the vinyl fluoride
      symmetry plane.

PMID- 24564453
TI  - Tuberculosis and HIV co-infection in children.
AB  - HIV is the top and tuberculosis is the second leading cause of death from
      infectious disease worldwide, with an estimated 8.7 million incident cases of
      tuberculosis and 2.5 million new HIV infections annually. The World Health
      Organization estimates that HIV prevalence among children with tuberculosis, in
      countries with moderate to high prevalence, ranges from 10 to 60%. The mechanisms
      promoting susceptibility of people with HIV to tuberculosis disease are
      incompletely understood, being likely caused by multifactorial processes.
      Paediatric tuberculosis and HIV have overlapping clinical manifestations, which
      could lead to missed or late diagnosis. Although every effort should be made to
      obtain a microbiologically-confirmed diagnosis in children with tuberculosis, in
      reality this may only be achieved in a minority, reflecting their paucibacillary
      nature and the difficulties in obtain samples. Rapid polymerase chain reaction
      tests, such as Xpert MTB/RIF assay, are increasingly used in children. The use of
      less or non invasive methods of sample collection, such as naso-pharyngeal
      aspirates and stool samples for a polymerase chain reaction-based diagnostic test
      tests and mycobacterial cultures is promising technique in HIV negative and HIV
      positive children. Anti-tuberculosis treatment should be started immediately at
      diagnosis with a four drug regimen, irrespective of the disease severity.
      Moreover, tuberculosis disease in an HIV infected child is considered to be a
      clinical indication for initiation of antiretroviral treatment. The World Health
      Organization recommends starting antiretroviral treatment in children as soon as
      anti-tuberculosis treatment is tolerated and within 2- 8 weeks after initiating
      it. The treatment of choice depends on the child's age and availability of age
      appropriate formulations, and potential drug interactions and resistance.
      Treatment of multidrug resistant tuberculosis in HIV-infected children follows
      same principles as for HIV uninfected children. There are conflicting results on
      effectiveness of isoniazid preventive therapy in reducing incidence of
      tuberculosis disease in children with HIV. CONCLUSION: Data on HIV/TB co
      infection in children are still lacking. There are on-going large clinical trials
      on the prevention and treatment of TB/HIV infection in children that hopefully
      will help to guide an evidence-based clinical practice in both resource-rich and
      resource-limited settings.HIV is the top and tuberculosis is the second leading
      cause of death from infectious disease worldwide, with an estimated 8.7 million
      incident cases of tuberculosis and 2.5 million new HIV infections annually. The
      World Health Organization estimates that HIV prevalence among children with
      tuberculosis, in countries with moderate to high prevalence, ranges from 10 to
      60%. The mechanisms promoting susceptibility of people with HIV to tuberculosis
      disease are incompletely understood, being likely caused by multifactorial
      processes.

PMID- 24564455
TI  - Effect of multiple access tracts during percutaneous nephrolithotomy on renal
      function: evaluation of risk factors for renal function deterioration.
AB  - PURPOSE: To assess the impact of multiple access tracts during percutaneous
      nephrolithotomy (PCNL) on short- and midterm renal function, and to determine
      risk factors predicting renal function deterioration and/or recoverability.
      PATIENTS AND METHODS: Patients undergoing PCNL with multiple punctures were
      prospectively enrolled. Preoperative evaluation included dimercaptosuccinic acid
      and diethylenetriaminepentaacetic acid renography. Patients were classified
      according to baseline renal function into patients with normal (<1.4 mg/dL) serum
      creatinine (group A) and patients with elevated (>=1.4 mg/dL) serum creatinine
      (group B). Patients were followed with serial serum creatinine evaluations and a
      repeated renography at 12 months. Factors evaluated for possible impact on renal
      function changes included preoperative renal function, number of access tracts,
      hypertension, and diabetes mellitus. RESULTS: There were 102 patients 21 to 65
      (mean 39.9) years who completed the study. Fifty patients (group A) had normal
      preoperative serum creatinine levels and glomerular filtration rate (GFR), which
      showed no statistically significant change 12 months after PCNL. Fifty-two
      patients had baseline renal impairment (group B), and they experienced
      statistically significant worsening of the serum creatinine level and GFR at 12
      months postoperatively (P<0.001). Ten (19.23%) patients in group B had a
      significant deterioration of GFR more than 25%. Independent risk factors for this
      poor outcome were elevated (>=1.4 mg/dL) preoperative serum creatinine level,
      diabetes, and hypertension. CONCLUSION: PCNL with multiple tracts carries a risk
      of adversely affecting renal function. Preoperative baseline renal impairment,
      diabetes, and hypertension are risk factors for significant renal function
      deterioration after the procedure.

PMID- 24564457
TI  - In silico experimental evolution: a tool to test evolutionary scenarios.
AB  - Comparative genomics has revealed that some species have exceptional genomes,
      compared to their closest relatives. For instance, some species have undergone a
      strong reduction of their genome with a drastic reduction of their genic
      repertoire. Deciphering the causes of these atypical trajectories can be very
      difficult because of the many phenomena that are intertwined during their
      evolution (e.g. changes of population size, environment structure and dynamics,
      selection strength, mutation rates...). Here we propose a methodology based on
      synthetic experiments to test the individual effect of these phenomena on a
      population of simulated organisms. We developed an evolutionary model--aevol--in
      which evolutionary conditions can be changed one at a time to test their effects
      on genome size and organization (e.g. coding ratio). To illustrate the proposed
      approach, we used aevol to test the effects of a strong reduction in the
      selection strength on a population of (simulated) bacteria. Our results show that
      this reduction of selection strength leads to a genome reduction of ~35% with a
      slight loss of coding sequences (~15% of the genes are lost--mainly those for
      which the contribution to fitness is the lowest). More surprisingly, under a low
      selection strength, genomes undergo a strong reduction of the noncoding
      compartment (~55% of the noncoding sequences being lost). These results are
      consistent with what is observed in reduced Prochlorococcus strains (marine
      cyanobacteria) when compared to close relatives.

PMID- 24564459
TI  - The moon illusion and size-distance scaling--evidence for shared neural patterns.
AB  - A moon near to the horizon is perceived larger than a moon at the zenith,
      although--obviously--the moon does not change its size. In this study, the neural
      mechanisms underlying the "moon illusion" were investigated using a virtual 3-D
      environment and fMRI. Illusory perception of an increased moon size was
      associated with increased neural activity in ventral visual pathway areas
      including the lingual and fusiform gyri. The functional role of these areas was
      further explored in a second experiment. Left V3v was found to be involved in
      integrating retinal size and distance information, thus indicating that the brain
      regions that dynamically integrate retinal size and distance play a key role in
      generating the moon illusion.

PMID- 24564458
TI  - Epigenetic modification, dehydration, and molecular crowding effects on the
      thermodynamics of i-motif structure formation from C-rich DNA.
AB  - DNA sequences with the potential to form secondary structures such as i-motifs
      (iMs) and G-quadruplexes (G4s) are abundant in the promoters of several oncogenes
      and, in some instances, are known to regulate gene expression. Recently, iM
      forming DNA strands have also been employed as functional units in nanodevices,
      ranging from drug delivery systems to nanocircuitry. To understand both the
      mechanism of gene regulation by iMs and how to use them more efficiently in
      nanotechnological applications, it is essential to have a thorough knowledge of
      factors that govern their conformational states and stabilities. Most of the
      prior work to characterize the conformational dynamics of iMs have been done with
      iM-forming synthetic constructs like tandem (CCT)n repeats and in standard dilute
      buffer systems. Here, we present a systematic study on the consequences of
      epigenetic modifications, molecular crowding, and degree of hydration on the
      stabilities of an iM-forming sequence from the promoter of the c-myc gene. Our
      results indicate that 5-hydroxymethylation of cytosines destabilized the iMs
      against thermal and pH-dependent melting; contrarily, 5-methylcytosine
      modification stabilized the iMs. Under molecular crowding conditions (PEG-300,
      40% w/v), the thermal stability of iMs increased by ~10  degrees C, and the pKa
      was raised from 6.1 +/- 0.1 to 7.0 +/- 0.1. Lastly, the iM's stability at varying
      degrees of hydration in 1,2-dimethoxyethane, 2-methoxyethanol, ethylene glycol,
      1,3-propanediol, and glycerol cosolvents indicated that the iMs are stabilized by
      dehydration because of the release of water molecules when folded. Our results
      highlight the importance of considering the effects of epigenetic modifications,
      molecular crowding, and the degree of hydration on iM structural dynamics. For
      example, the incorporation of 5-methylycytosines and 5-hydroxymethlycytosines in
      iMs could be useful for fine-tuning the pH- or temperature-dependent
      folding/unfolding of an iM. Variations in the degree of hydration of iMs may also
      provide an additional control of the folded/unfolded state of iMs without having
      to change the pH of the surrounding matrix.

PMID- 24564460
TI  - The effect of FEF microstimulation on the responses of neurons in the lateral
      intraparietal area.
AB  - The macaque FEFs and the lateral intraparietal area (LIP) are high-level cortical
      areas involved in both spatial attention and oculomotor behavior. Stimulating FEF
      at a level below the threshold for evoking saccades increases fMRI activity and
      gamma power in area LIP, but the precise effect exerted by the FEF on LIP neurons
      is unknown. In our study, we recorded LIP single-unit activity during a visually
      guided saccade task with a peripherally presented go signal during
      microstimulation of FEF. We found that FEF microstimulation increased the LIP
      spike rate immediately after the highly salient go signal inside the LIP
      receptive field when both target and go signal were presented inside the
      receptive field, and no other possible go cues were present on the screen. The
      effect of FEF microstimulation on the LIP response was positive until at least
      800 msec after microstimulation had ceased, but reversed for longer trial
      durations. Therefore, FEF microstimulation can modulate the LIP spike rate only
      when attention is selectively directed toward the stimulated location. These
      results provide the first direct evidence for LIP spike rate modulations caused
      by FEF microstimulation, thus showing that FEF activity can be the source of top
      down control of area LIP. 

PMID- 24564461
TI  - A functional polymorphism of the MAOA gene is associated with neural responses to
      induced anger control.
AB  - Aggressiveness is highly heritable. Recent experimental work has linked
      individual differences in a functional polymorphism of the monoamine oxidase-A
      gene (MAOA) to anger-driven aggression. Other work has implicated the dorsal ACC
      (dACC) in cognitive-emotional control and the amygdala in emotional arousal. The
      present imaging genetics study investigated dACC and amygdala reactivity to
      induced anger control as a function of MAOA genotype. A research assistant asked
      38 healthy male undergraduates to control their anger in response to an insult by
      a rude experimenter. Men with the low-expression allele showed increased dACC and
      amygdala activation after the insult, but men with the high-expression allele did
      not. Both dACC and amygdala activation independently mediated the relationship
      between MAOA genotype and self-reported anger control. Moreover, following the
      insult, men with the high-functioning allele showed functional decoupling between
      the amygdala and dACC, but men with the low-functioning allele did not. These
      results suggest that heightened dACC and amygdala activation and their
      connectivity are neuroaffective mechanisms underlying anger control in
      participants with the low-functioning allele of the MAOA gene.

PMID- 24564463
TI  - The neural coding of feedback learning across child and adolescent development.
AB  - The ability to learn from environmental cues is an important contributor to
      successful performance in a variety of settings, including school. Despite the
      progress in unraveling the neural correlates of cognitive control in childhood
      and adolescence, relatively little is known about how these brain regions
      contribute to learning. In this study, 268 participants aged 8-25 years performed
      a rule-learning task with performance feedback in a 3T MRI scanner. We examined
      the development of the frontoparietal network during feedback learning by
      exploring contributions of age and pubertal development. The pFC showed more
      activation following negative compared with positive feedback with increasing
      age. In contrast, our data suggested that the parietal cortex demonstrated a
      shift from sensitivity to positive feedback in young children to negative
      feedback in adolescents and adults. These findings were interpreted in terms of
      separable contributions of the frontoparietal network in childhood to more
      integrated functions in adulthood. Puberty (testosterone, estradiol, and self
      report) did not explain additional variance in neural activation patterns above
      age, suggesting that development of the frontoparietal network occurs relatively
      independently from hormonal development. This study presents novel insights into
      the development of learning, moving beyond a simple frontoparietal immaturity
      hypothesis. 

PMID- 24564464
TI  - The role of right prefrontal and medial cortex in response inhibition:
      interfering with action restraint and action cancellation using transcranial
      magnetic brain stimulation.
AB  - The ability of inhibiting impulsive urges is paramount for human behavior. Such
      successful response inhibition has consistently been associated with activity in
      pFC. The current study aims to unravel the differential involvement of different
      areas within right pFC for successful action restraint versus action
      cancellation. These two conceptually different aspects of action inhibition were
      measured with a go/no-go task (action restraint) and a stop signal task (action
      cancellation). Localization of relevant prefrontal activation was based on fMRI
      data. Significant task-related activation during successful action restraint was
      localized for each participant individually in right anterior insula (rAI), right
      superior frontal gyrus, and pre-SMA. Activation during successful action
      cancellation was localized in rAI, right middle frontal gyrus, and pre-SMA.
      Subsequently, fMRI-guided continuous thetaburst stimulation was applied to these
      regions. Results showed that the disruption of neural activity in rAI reduced
      both the ability to restrain (go/no-go) and cancel (stop signal) responses. In
      contrast, continuous thetaburst stimulation-induced disruption of the right
      superior frontal gyrus specifically impaired the ability to restrain from
      responding (go/no-go), while leaving the ability for action cancellation largely
      intact. Stimulation applied to right middle frontal gyrus and pre-SMA did not
      affect inhibitory processing in neither of the two tasks. These findings provide
      a more comprehensive perspective on the role of pFC in inhibition and cognitive
      control. The results emphasize the role of inferior frontal regions for global
      inhibition, whereas superior frontal regions seem to be specifically relevant for
      successful action restraint. 

PMID- 24564465
TI  - Associative recognition processes are modulated by modality relations.
AB  - Although memory of episodic associations is generally considered to be
      recollective in nature, it has been suggested that when stimuli are experienced
      as a unit, familiarity-related processes might contribute to their subsequent
      associative recognition. Furthermore, intradomain associations are believed to be
      unitized more readily than interdomain associations. To assess these claims, we
      tested associative recognition following two types of pair associate learning. In
      the unimodal task, stimulus pairs were pictures of common objects, whereas in the
      cross-modal task, stimulus pairs consisted of an object picture and an unrelated
      environmental sound. At test, participants discriminated intact from recombined
      pairs while ERPs were recorded. In the unimodal task only, associative
      recognition was accompanied by a robust frontal deflection reminiscent of a
      component commonly interpreted as related to familiarity processes. In contrast,
      ERP correlates of associative recognition observed at more posterior sites, akin
      to a component that has been related to recollection, were apparent in both
      tasks. These findings indicate that retrieval of unimodal associations can be
      supported by familiarity-related processes that are dissociable from recollective
      processes required for the retrieval of cross-modal associations. 

PMID- 24564462
TI  - Spatiotemporal dynamics of online motor correction processing revealed by high
      density electroencephalography.
AB  - The ability to control online motor corrections is key to dealing with unexpected
      changes arising in the environment with which we interact. How the CNS controls
      online motor corrections is poorly understood, but evidence has accumulated in
      favor of a submovement-based model in which apparently continuous movement is
      segmented into distinct submovements. Although most studies have focused on
      submovements' kinematic features, direct links with the underlying neural
      dynamics have not been extensively explored. This study sought to identify an
      electroencephalographic signature of submovements. We elicited kinematic
      submovements using a double-step displacement paradigm. Participants moved their
      wrist toward a target whose direction could shift mid-movement with a 50%
      probability. Movement kinematics and cortical activity were concurrently recorded
      with a low-friction robotic device and high-density electroencephalography.
      Analysis of spatiotemporal dynamics of brain activation and its correlation with
      movement kinematics showed that the production of each kinematic submovement was
      accompanied by (1) stereotyped topographic scalp maps and (2) frontoparietal ERPs
      time-locked to submovements. Positive ERP peaks from frontocentral areas
      contralateral to the moving wrist preceded kinematic submovement peaks by 220-250
      msec and were followed by positive ERP peaks from contralateral parietal areas
      (140-250 msec latency, 0-80 msec before submovement peaks). Moreover, individual
      subject variability in the latency of frontoparietal ERP components following the
      target shift significantly predicted variability in the latency of the corrective
      submovement. Our results are in concordance with evidence for the intermittent
      nature of continuous movement and elucidate the timing and role of frontoparietal
      activations in the generation and control of corrective submovements. 

PMID- 24564466
TI  - Ventral striatum and the evaluation of memory retrieval strategies.
AB  - Adaptive memory retrieval requires mechanisms of cognitive control that
      facilitate the recovery of goal-relevant information. Frontoparietal systems are
      known to support control of memory retrieval. However, the mechanisms by which
      the brain acquires, evaluates, and adapts retrieval strategies remain unknown.
      Here, we provide evidence that ventral striatal activation tracks the success of
      a retrieval strategy and correlates with subsequent reliance on that strategy.
      Human participants were scanned with fMRI while performing a lexical decision
      task. A rule was provided that indicated the likely semantic category of a target
      word given the category of a preceding prime. Reliance on the rule improved
      decision-making, as estimated within a drift diffusion framework. Ventral
      striatal activation tracked the benefit that relying on the rule had on decision
      making. Moreover, activation in ventral striatum correlated with a participant's
      subsequent reliance on the rule. Taken together, these results support a role for
      ventral striatum in learning and evaluating declarative retrieval strategies. 

PMID- 24564469
TI  - Opposing effects of appetitive and aversive cues on go/no-go behavior and motor
      excitability.
AB  - Everyday life, as well as psychiatric illness, is replete with examples where
      appetitive and aversive stimuli hijack the will, leading to maladaptive behavior.
      Yet the mechanisms underlying this phenomenon are not well understood. Here we
      investigate how motivational cues influence action tendencies in healthy
      individuals with a novel paradigm. Behaviorally, we observed that an appetitive
      cue biased go behavior (making a response), whereas an aversive cue biased no-go
      behavior (withholding a response). We hypothesized that the origin of this
      behavioral go/no-go bias occurs at the motor system level. To test this, we used
      single-pulse TMS as a motor system probe (rather than a disruptive tool) to index
      motivational biasing. We found that the appetitive cue biased the participants to
      go more by relatively increasing motor system excitability, and that the aversive
      cue biased participants to no-go more by relatively decreasing motor system
      excitability. These results show, first, that maladaptive behaviors arise from
      motivational cues quickly spilling over into the motor system and biasing
      behavior even before action selection and, second, that this occurs in opposing
      directions for appetitive and aversive cues. 

PMID- 24564468
TI  - Come together, right now: dynamic overwriting of an object's history through
      common fate.
AB  - The objects around us constantly move and interact, and the perceptual system
      needs to monitor on-line these interactions and to update the object's status
      accordingly. Gestalt grouping principles, such as proximity and common fate, play
      a fundamental role in how we perceive and group these objects. Here, we
      investigated situations in which the initial object representation as a separate
      item was updated by a subsequent Gestalt grouping cue (i.e., proximity or common
      fate). We used a version of the color change detection paradigm, in which the
      objects started to move separately, then met and stayed stationary, or moved
      separately, met, and then continued to move together. We monitored the object
      representations on-line using the contralateral delay activity (CDA; an ERP
      component indicative of the number of maintained objects), during their movement,
      and after the objects disappeared and became working memory representations. The
      results demonstrated that the objects' representations (as indicated by the CDA
      amplitude) persisted as being separate, even after a Gestalt proximity cue (when
      the objects "met" and remained stationary on the same position). Only a strong
      common fate Gestalt cue (when the objects not just met but also moved together)
      was able to override the objects' initial separate status, creating an integrated
      representation. These results challenge the view that Gestalt principles cause
      reflexive grouping. Instead, the object initial representation plays an important
      role that can override even powerful grouping cues. 

PMID- 24564467
TI  - Brain mechanisms of successful recognition through retrieval of semantic context.
AB  - Episodic memory is associated with the encoding and retrieval of context
      information and with a subjective sense of reexperiencing past events. The neural
      correlates of episodic retrieval have been extensively studied using fMRI,
      leading to the identification of a "general recollection network" including
      medial temporal, parietal, and prefrontal regions. However, in these studies, it
      is difficult to disentangle the effects of context retrieval from recollection.
      In this study, we used fMRI to determine the extent to which the recruitment of
      regions in the recollection network is contingent on context reinstatement.
      Participants were scanned during a cued recognition test for target words from
      encoded sentences. Studied target words were preceded by either a cue word
      studied in the same sentence (thus congruent with encoding context) or a cue word
      studied in a different sentence (thus incongruent with encoding context).
      Converging fMRI results from independently defined ROIs and whole-brain analysis
      showed regional specificity in the recollection network. Activity in hippocampus
      and parahippocampal cortex was specifically increased during successful retrieval
      following congruent context cues, whereas parietal and prefrontal components of
      the general recollection network were associated with confident retrieval
      irrespective of contextual congruency. Our findings implicate medial temporal
      regions in the retrieval of semantic context, contributing to, but dissociable
      from, recollective experience. 

PMID- 24564471
TI  - Activity in the nucleus accumbens and amygdala underlies individual differences
      in prosocial and individualistic economic choices.
AB  - Much decision-making requires balancing benefits to the self with benefits to the
      group. There are marked individual differences in this balance such that
      individualists tend to favor themselves whereas prosocials tend to favor the
      group. Understanding the mechanisms underlying this difference has important
      implications for society and its institutions. Using behavioral and fMRI data
      collected during the performance of the ultimatum game, we show that individual
      differences in social preferences for resource allocation, so-called "social
      value orientation," is linked with activity in the nucleus accumbens and amygdala
      elicited by inequity, rather than activity in insula, ACC, and dorsolateral pFC.
      Importantly, the presence of cognitive load made prosocials behave more
      prosocially and individualists more individualistically, suggesting that social
      value orientation is driven more by intuition than reflection. In parallel,
      activity in the nucleus accumbens and amygdala, in response to inequity, tracked
      this behavioral pattern of prosocials and individualists. In addition, we
      conducted an impunity game experiment with different participants where they
      could not punish unfair behavior and found that the inequity-correlated activity
      seen in prosocials during the ultimatum game disappeared. This result suggests
      that the accumbens and amygdala activity of prosocials encodes "outcome-oriented
      emotion" designed to change situations (i.e., achieve equity or punish).
      Together, our results suggest a pivotal contribution of the nucleus accumbens and
      amygdala to individual differences in sociality. 

PMID- 24564470
TI  - Regions of mid-level human visual cortex sensitive to the global coherence of
      local image patches.
AB  - The global structural arrangement and spatial layout of the visual environment
      must be derived from the integration of local signals represented in the lower
      tiers of the visual system. This interaction between the spatially local and
      global properties of visual stimulation underlies many of our visual capacities,
      and how this is achieved in the brain is a central question for visual and
      cognitive neuroscience. Here, we examine the sensitivity of regions of the
      posterior human brain to the global coordination of spatially displaced
      naturalistic image patches. We presented observers with image patches in two
      circular apertures to the left and right of central fixation, with the patches
      drawn from either the same (coherent condition) or different (noncoherent
      condition) extended image. Using fMRI at 7T (n = 5), we find that global
      coherence affected signal amplitude in regions of dorsal mid-level cortex.
      Furthermore, we find that extensive regions of mid-level visual cortex contained
      information in their local activity pattern that could discriminate coherent and
      noncoherent stimuli. These findings indicate that the global coordination of
      local naturalistic image information has important consequences for the
      processing in human mid-level visual cortex. 

PMID- 24564472
TI  - Analysis of the intestinal microbiota using SOLiD 16S rRNA gene sequencing and
      SOLiD shotgun sequencing.
AB  - BACKGROUND: Metagenomics seeks to understand microbial communities and
      assemblages by DNA sequencing. Technological advances in next generation
      sequencing technologies are fuelling a rapid growth in the number and scope of
      projects aiming to analyze complex microbial environments such as marine, soil or
      the gut. Recent improvements in longer read lengths and paired-sequencing allow
      better resolution in profiling microbial communities. While both 454 sequencing
      and Illumina sequencing have been used in numerous metagenomic studies, SOLiD
      sequencing is not commonly used in this area, as it is believed to be more
      suitable in the context of reference-guided projects. RESULTS: To investigate the
      performance of SOLiD sequencing in a metagenomic context, we compared taxonomic
      profiles of SOLiD mate-pair sequencing reads with Sanger paired reads and 454
      single reads. All sequences were obtained from the bacterial 16S rRNA gene, which
      was amplified from microbial DNA extracted from a human fecal sample.
      Additionally, from the same fecal sample, complete genomic microbial DNA was
      extracted and shotgun sequenced using SOLiD sequencing to study the composition
      of the intestinal microbiota and the existing microbial metabolism. We found that
      the microbiota composition of 16S rRNA gene sequences obtained using Sanger, 454
      and SOLiD sequencing provide results comparable to the result based on shotgun
      sequencing. Moreover, with SOLiD sequences we obtained more resolution down to
      the species level. In addition, the shotgun data allowed us to determine a
      functional profile using the databases SEED and KEGG. CONCLUSIONS: This study
      shows that SOLiD mate-pair sequencing is a viable and cost-efficient option for
      analyzing a complex microbiome. To the best of our knowledge, this is the first
      time that SOLiD sequencing has been used in a human sample.

PMID- 24564473
TI  - Proteomic analysis of cross protection provided between cold and osmotic stress
      in Listeria monocytogenes.
AB  - Listeria monocytogenes is a Gram-positive, foodborne pathogen responsible for
      approximately 28% of all food-related deaths each year in the United States. L.
      monocytogenes infections are linked to the consumption of minimally processed
      ready-to-eat (RTE) products such as cheese, deli meats, and cold-smoked finfish
      products. L. monocytogenes is resistant to stresses commonly encountered in the
      food-processing environment, including low pH, high salinity, oxygen content, and
      various temperatures. The purpose of this study was to determine if cells
      habituated at low temperatures would result in cross-protective effects against
      osmotic stress. We found that cells exposed to refrigerated temperatures prior to
      a mild salt stress treatment had increased survival in NaCl concentrations of 3%.
      Additionally, the longer the cells were pre-exposed to cold temperatures, the
      greater the increase in survival in 3% NaCl. A proteomics analysis was performed
      in triplicate in order to elucidate mechanisms involved in cold-stress induced
      cross protection against osmotic stress. Proteins involved in maintenance of the
      cell wall and cellular processes, such as penicillin binding proteins and
      osmolyte transporters, and processes involving amino acid metabolism, such as
      osmolyte synthesis, transport, and lipid biosynthesis, had the greatest increase
      in expression when cells were exposed to cold temperatures prior to salt. By
      gaining a better understanding of how this pathogen adapts physiologically to
      various environmental conditions, improvements can be made in detection and
      mitigation strategies. 

PMID- 24564475
TI  - It 'did what it said on the tin' - participant's views of the content and process
      of donor conception parenthood preparation workshops.
AB  - Using donor conception treatment for family building brings challenges as well as
      rewards. As social model approaches to managing genetic difference within
      families gradually replace earlier medical models, parents are encouraged to be
      open with their children about their origins amidst greater social acceptance.
      Little is known about effective interventions to help prospective parents prepare
      for such family life. A survey was sent to participants in 16 Preparation for
      Parenthood workshops run in England by Donor Conception Network, a peer support
      organisation, between 2008 and 2010. The 79 respondents (32.4% response) included
      heterosexual couples, lesbian couples and single women considering sperm, egg or
      double donation. In 86% couples, both partners responded. The use of a range of
      techniques, a family lifespan approach, facilitators with personal as well as
      professional experience, medical and psychosocial specialists, and access to peer
      support were well received. Results suggest the value of attending cognitive and
      affective processes, acknowledging the impact of stigma and discussing how the
      donor's biography/presence can be conjoined with that of the new family. Findings
      suggest workshop approaches to donor conception parenthood preparation can be
      useful for prospective lesbian/single women/heterosexual-headed families
      considering donor conception. Such interventions have not previously been
      reported.

PMID- 24564474
TI  - The looks of an odour--visualising neural odour response patterns in real time.
AB  - BACKGROUND: Calcium imaging in insects reveals the neural response to odours,
      both at the receptor level on the antenna and in the antennal lobe, the first
      stage of olfactory information processing in the brain. Changes of intracellular
      calcium concentration in response to odour presentations can be observed by
      employing calcium-sensitive, fluorescent dyes. The response pattern across all
      recorded units is characteristic for the odour. METHOD: Previously, extraction of
      odour response patterns from calcium imaging movies was performed offline, after
      the experiment. We developed software to extract and to visualise odour response
      patterns in real time. An adaptive algorithm in combination with an
      implementation for the graphics processing unit enables fast processing of movie
      streams. Relying on correlations between pixels in the temporal domain, the
      calcium imaging movie can be segmented into regions that correspond to the neural
      units. RESULTS: We applied our software to calcium imaging data recorded from the
      antennal lobe of the honeybee Apis mellifera and from the antenna of the fruit
      fly Drosophila melanogaster. Evaluation on reference data showed results
      comparable to those obtained by previous offline methods while computation time
      was significantly lower. Demonstrating practical applicability, we employed the
      software in a real-time experiment, performing segmentation of glomeruli--the
      functional units of the honeybee antennal lobe--and visualisation of glomerular
      activity patterns. CONCLUSIONS: Real-time visualisation of odour response
      patterns expands the experimental repertoire targeted at understanding
      information processing in the honeybee antennal lobe. In interactive experiments,
      glomeruli can be selected for manipulation based on their present or past
      activity, or based on their anatomical position. Apart from supporting
      neurobiology, the software allows for utilising the insect antenna as a
      chemosensor, e.g. to detect or to classify odours.

PMID- 24564476
TI  - Proposing a highly accurate protein structural class predictor using segmentation
      based features.
AB  - BACKGROUND: Prediction of the structural classes of proteins can provide
      important information about their functionalities as well as their major tertiary
      structures. It is also considered as an important step towards protein structure
      prediction problem. Despite all the efforts have been made so far, finding a fast
      and accurate computational approach to solve protein structural class prediction
      problem still remains a challenging problem in bioinformatics and computational
      biology. RESULTS: In this study we propose segmented distribution and segmented
      auto covariance feature extraction methods to capture local and global
      discriminatory information from evolutionary profiles and predicted secondary
      structure of the proteins. By applying SVM to our extracted features, for the
      first time we enhance the protein structural class prediction accuracy to over
      90% and 85% for two popular low-homology benchmarks that have been widely used in
      the literature. We report 92.2% and 86.3% prediction accuracies for 25PDB and
      1189 benchmarks which are respectively up to 7.9% and 2.8% better than previously
      reported results for these two benchmarks. CONCLUSION: By proposing segmented
      distribution and segmented auto covariance feature extraction methods to capture
      local and global discriminatory information from evolutionary profiles and
      predicted secondary structure of the proteins, we are able to enhance the protein
      structural class prediction performance significantly.

PMID- 24564478
TI  - Transition-metal-catalyzed carbonylation reactions of olefins and alkynes: a
      personal account.
AB  - Carbon monoxide was discovered and identified in the 18th century. Since the
      first applications in industry 80 years ago, academic and industrial laboratories
      have broadly explored CO's use in chemical reactions. Today organic chemists
      routinely employ CO in organic chemistry to synthesize all kinds of carbonyl
      compounds. Despite all these achievements and a century of carbonylation
      catalysis, many important research questions and challenges remain. Notably,
      apart from academic developments, industry applies carbonylation reactions with
      CO on bulk scale. In fact, today the largest applications of homogeneous
      catalysis (regarding scale) are carbonylation reactions, especially
      hydroformylations. In addition, the vast majority of acetic acid is produced via
      carbonylation of methanol (Monsanto or Cativa process). The carbonylation of
      olefins/alkynes with nucleophiles, such as alcohols and amines, represent another
      important type of such reactions. In this Account, we discuss our work on various
      carbonylations of unsaturated compounds and related reactions. Rhodium-catalyzed
      isomerization and hydroformylation reactions of internal olefins provide
      straightforward access to higher value aldehydes. Catalytic
      hydroaminomethylations offer an ideal way to synthesize substituted amines and
      even heterocycles directly. More recently, our group has also developed so-called
      alternative metal catalysts based on iridium, ruthenium, and iron. What about the
      future of carbonylation reactions? CO is already one of the most versatile C1
      building blocks for organic synthesis and is widely used in industry. However,
      because of CO's high toxicity and gaseous nature, organic chemists are often
      reluctant to apply carbonylations more frequently. In addition, new regulations
      have recently made the transportation of carbon monoxide more difficult. Hence,
      researchers will need to develop and more frequently use practical and benign CO
      generating reagents. Apart from formates, alcohols, and metal carbonyls, carbon
      dioxide also offers interesting options. Industrial chemists seek easy to prepare
      catalysts and patent-free ligands/complexes. In addition, non-noble metal
      complexes will interest both academic and industrial researchers. The novel
      Lucite process for methyl methacrylate is an important example of an improved
      catalyst. This reaction makes use of a specific palladium/bisphosphine catalyst,
      which led to the successful implementation of the technology. More active and
      productive catalysts for related carbonylations of less reactive olefins would
      allow for other large scale applications of this methodology. From an academic
      point of view, researchers continue to look for selective reactions with more
      functionalized olefins. Finally, because of the volatility of simple metal
      carbonyl complexes, carbonylation reactions today remain a domain of homogeneous
      catalysis. The invention of more stable and recyclable heterogeneous catalysts or
      metal-free carbonylations (radical carbonylations) will be difficult, but could
      offer interesting challenges for young chemists. 

PMID- 24564477
TI  - MetaSel: a metaphase selection tool using a Gaussian-based classification
      technique.
AB  - BACKGROUND: Identification of good metaphase spreads is an important step in
      chromosome analysis for identifying individuals with genetic disorders. The
      process of finding suitable metaphase chromosomes for accurate clinical analysis
      is, however, very time consuming since they are selected manually. The selection
      of suitable metaphase chromosome spreads thus represents a major bottleneck for
      conventional cytogenetic analysis. Although many algorithms have been developed
      for karyotyping, none have adequately addressed the critical bottleneck of
      selecting suitable chromosome spreads. In this paper, we present a software tool
      that uses a simple rule-based system to efficiently identify metaphase spreads
      suitable for karyotyping. RESULTS: The chromosome shapes can be classified by the
      software into four main classes. The first and the second classes refer to
      individual chromosomes with straight and skewed shapes, respectively. The third
      class is characterized as those chromosomes with overlapping bodies and the
      fourth class is for the non-chromosome objects. Good metaphase spreads should
      largely contain chromosomes of the first and the second classes, while the third
      class should be kept minimal. Several image parameters were examined and used for
      creating rule-based classification. The threshold value for each parameter is
      determined using a statistical model. We observed that the Gaussian model can
      represent the empirical probability density function of the parameters and,
      hence, the threshold value can be easily determined. The proposed rules can
      efficiently and accurately classify the individual chromosome with > 90%
      accuracy. CONCLUSIONS: The software tool, termed MetaSel, was developed. Using
      the Gaussian-based rules, the tool can be used to quickly rank hundreds of
      chromosome spread images so as to assist cytogeneticists to perform karyotyping
      effectively. Furthermore, MetaSel offers an intuitive, yet comprehensive,
      workflow to assist karyotyping, including tools for editing chromosome (split,
      merge and fix) and a karyotyping editor (moving, rotating, and pairing homologous
      chromosomes). The program can be freely downloaded from
      "http://www4a.biotec.or.th/GI/tools/metasel".

PMID- 24564480
TI  - Endogenous endophthalmitis by Chrysosporium: an opportunistic pathogen.

PMID- 24564481
TI  - Preferential positioning of dopants and co-dopants in embedded and freestanding
      Si nanocrystals.
AB  - In this work we aim at understanding the effect of n- and p-type substitutional
      doping in the case of matrix-embedded and freestanding Si nanocrystals. By means
      of ab initio calculations we identify the preferential positioning of the dopants
      and its effect on the structural properties with respect to the undoped case.
      Subsequently, we consider the case of phosphorus and boron co-doped nanocrystals
      showing that, against the single-doping situation, the energetics strongly favors
      the binding of the impurities at the nanocrystal surface. Indeed we demonstrate
      that the polar B-P bond forms a stable permanent electric dipole that radially
      points inward in the nanocrystal. Such a noteworthy characteristic and its
      physical consequences are discussed alongside new potential applications. 

PMID- 24564479
TI  - QChIPat: a quantitative method to identify distinct binding patterns for two
      biological ChIP-seq samples in different experimental conditions.
AB  - BACKGROUND: Many computational programs have been developed to identify enriched
      regions for a single biological ChIP-seq sample. Given that many biological
      questions are often asked to compare the difference between two different
      conditions, it is important to develop new programs that address the comparison
      of two biological ChIP-seq samples. Despite several programs designed to address
      this question, these programs suffer from some drawbacks, such as inability to
      distinguish whether the identified differential enriched regions are indeed
      significantly enriched, lack of distinguishing binding patterns, and neglect of
      the normalization between samples. RESULTS: In this study, we developed a novel
      quantitative method for comparing two biological ChIP-seq samples, called
      QChIPat. Our method employs a new global normalization method: nonparametric
      empirical Bayes (NEB) correction normalization, utilizes pre-defined enriched
      regions identified from single-sample peak calling programs, uses statistical
      methods to define differential enriched regions, then defines binding (histone
      modification) pattern information for those differential enriched regions. Our
      program was tested on a benchmark data: histone modifications data used by
      ChIPDiffs. It was then applied on two study cases: one to identify differential
      histone modification sites for ChIP-seq of H3K27me3 and H3K9me2 data in AKT1
      transfected MCF10A cells; the other to identify differential binding sites for
      ChIP-seq of TCF7L2 data in MCF7 and PANC1 cells. CONCLUSIONS: Several advantages
      of our program include: 1) it considers a control (or input) experiment; 2) it
      incorporates a novel global normalization strategy: nonparametric empirical Bayes
      correction normalization; 3) it provides the binding pattern information among
      different enriched regions. QChIPat is implemented in R, Perl and C++, and has
      been tested under Linux. The R package is available at http://motif.bmi.ohio
      state.edu/QChIPat.

PMID- 24564483
TI  - Gender differences in the experiences of HIV/AIDS-related stigma: a qualitative
      study in Ghana.
AB  - Globally more women have been diagnosed with HIV/AIDS and are more likely to be
      stigmatized than men, especially in male-dominant societies. Gender differences
      in the experience of HIV-related stigma, however, have not been extensively
      explored. Researchers investigate the gender differences in HIV/AIDS-related
      stigma experiences here. Interviews were conducted with eight HIV patients and
      their nine discordant family members in Ghana. Our findings include gender
      differences in disclosure and response to HIV/AIDS diagnosis. The negative impact
      of HIV-related stigma was found to be more extensive for women than for men. Our
      findings may be used to facilitate an awareness and understanding through which
      supportive interventions can be implemented. 

PMID- 24564482
TI  - Toolboxes for a standardised and systematic study of glycans.
AB  - BACKGROUND: Recent progress in method development for characterising the branched
      structures of complex carbohydrates has now enabled higher throughput technology.
      Automation of structure analysis then calls for software development since adding
      meaning to large data collections in reasonable time requires corresponding
      bioinformatics methods and tools. Current glycobioinformatics resources do cover
      information on the structure and function of glycans, their interaction with
      proteins or their enzymatic synthesis. However, this information is partial,
      scattered and often difficult to find to for non-glycobiologists. METHODS:
      Following our diagnosis of the causes of the slow development of
      glycobioinformatics, we review the "objective" difficulties encountered in
      defining adequate formats for representing complex entities and developing
      efficient analysis software. RESULTS: Various solutions already implemented and
      strategies defined to bridge glycobiology with different fields and integrate the
      heterogeneous glyco-related information are presented. CONCLUSIONS: Despite the
      initial stage of our integrative efforts, this paper highlights the rapid
      expansion of glycomics, the validity of existing resources and the bright future
      of glycobioinformatics.

PMID- 24564485
TI  - Quinoidal naphtho[1,2-b:5,6-b']dithiophenes for solution-processed n-channel
      organic field-effect transistors.
AB  - A series of new quinoidal naphthodithiophenes, 2,7-bis(alpha,alpha
      dicyanomethylene)-2,7-dihydronaphtho[1,2-b:5,6-b']dithiophenes, in which all the
      four fused aromatic rings are incorporated into the quinoidal system, were
      synthesized and evaluated as an n-channel organic semiconductor. Solution
      processed field-effect transistors exhibited typical n-channel transistor
      characteristics with the mobility as high as 0.1 cm(2) V(-1) s(-1), which is
      higher by more than 1 order of magnitude than those reported for isomeric
      quinoidal naphthodithiophenes having a naphthoquinoidal structure. 

PMID- 24564484
TI  - The associations of birth intervals with small-for-gestational-age, preterm, and
      neonatal and infant mortality: a meta-analysis.
AB  - BACKGROUND: Short and long birth intervals have previously been linked to adverse
      neonatal outcomes. However, much of the existing literature uses cross-sectional
      studies, from which deriving causal inference is complex. We examine the
      association between short/long birth intervals and adverse neonatal outcomes by
      calculating and meta-analyzing associations using original data from cohort
      studies conducted in low-and middle-income countries (LMIC). METHODS: We
      identified five cohort studies. Adjusted odds ratios (aOR) were calculated for
      each study, with birth interval as the exposure and small-for-gestational-age
      (SGA) and/or preterm birth, and neonatal and infant mortality as outcomes. The
      associations were controlled for potential confounders and meta-analyzed.
      RESULTS: Birth interval of shorter than 18 months had statistically significant
      increased odds of SGA (pooled aOR: 1.51, 95% CI: 1.31-1.75), preterm (pooled aOR:
      1.58, 95% CI: 1.19-2.10) and infant mortality (pooled aOR: 1.83, 95% CI: 1.19
      2.81) after controlling for potential confounding factors (reference 36-<60
      months). It was also significantly associated with term-SGA, preterm-appropriate
      for-gestational-age, and preterm-SGA. Birth interval over 60 months had increased
      risk of SGA (pooled aOR: 1.22, 95% CI: 1.07-1.39) and term-SGA (pooled aOR: 1.14,
      95% CI: 1.03-1.27), but was not associated with other outcomes. CONCLUSIONS:
      Birth intervals shorter than 18 months are significantly associated with SGA,
      preterm birth and death in the first year of life. Lack of access to family
      planning interventions thus contributes to the burden of adverse birth outcomes
      and infant mortality in LMICs. Programs and policies must assess ways to provide
      equitable access to reproductive health interventions to mothers before or soon
      after delivering a child, but also address underlying socioeconomic factors that
      may modify and worsen the effect of short intervals.

PMID- 24564487
TI  - In vitro evaluation of the occlusive properties of latex-covered amplatzer
      vascular plugs for transrenal ureteral occlusion.
AB  - PURPOSE: To evaluate the occlusive properties of latex-covered Amplatzer Vascular
      Plugs (AVPs) for transrenal ureteral occlusion in vitro. MATERIALS AND METHODS:
      Latex-covered AVPs type I and II (diameter 8, 10, 12, 14, and 16 mm) were used as
      occlusive devices. Radial force of an AVP was measured using simulated ureteral
      diameters of 4 to 12 mm. Occlusive properties were examined in a silicone tube
      (inner diameter 6 mm) with measurement of drainage time of a 40 cm water column.
      In complete occlusion, the maximum pressure that the plug was able to withstand
      was determined at different temperature levels. Statistical analysis of drainage
      time was performed in a general linear model (GLM) and using correlation
      analyses. Explanted porcine ureters were used to simulate physiologic conditions.
      Pressure measurements were performed until leakage, plug dislocation, or rupture
      of the ureter occurred. RESULTS: Radial force depended on AVP type, size,
      ureteral diameter, and temperature. The 16-mm AVP II showed the highest radial
      force of more than 5 N (ureteral diameter 4 mm, body temperature). All AVP I
      showed water leakage and plug dislocation. Drainage time of the AVP II depended
      significantly on plug size and temperature and correlated with radial force
      (r=0.731, P<0.001). In complete occlusion, water leakage occurred at 500 to 1000
      cm H2O and dislocation between 500 to more than 2000 cm H2O. In porcine ureters,
      leakage occurred at room temperature between 19 to 93 cm H2O. At body
      temperature, all AVP II occluded the ureter completely. CONCLUSION: Latex-covered
      AVP II (diameter 8-16 mm) can effectively occlude the ureter, especially
      considering remodeling of the nitinol at body temperature. Large plug diameters
      can exert enough radial force even in dilated ureters to allow for successful
      occlusion. Because deployment of a 16-mm latex-covered AVP II can be technically
      difficult, we advocate the use of 12- or 14-mm AVP II for transrenal ureteral
      occlusion. AVP Is are not suitable for ureteral occlusion.

PMID- 24564488
TI  - Superspreaders versus "cousin" non-superspreaders: disjoining pressure in
      gravitational film drainage.
AB  - Gravitational drainage of vertical films supported on a wire frame of two
      superspreaders SILWET L-77 and BREAK-THRU S 278 and their respective "cousin" non
      superspreaders SILWET L-7607 and BREAK-THRU S 233 revealed drastic differences.
      The superspreader films showed complicated dynamic "turbulent"-like
      interferometric patterns in distinction from the ordered color bands of the
      "cousin" non-superspreaders, which resembled those of the ordinary surfactants.
      Nevertheless, the superspreader films stabilized themselves at the thickness
      about 35 nm and revealed an order of magnitude longer lifetime before bursting
      compared to that of the "cousin" non-superspreaders. Notably, the superspreaders
      revealed drastic differences from the non-superspreaders in aqueous solutions
      with no contact with any solid hydrophobic surface. The self-stabilization of the
      superspreader films is attributed to significant disjoining pressure probably
      related to long superspreader bilayers hanging from the free surfaces. The
      scaling law for the disjoining pressure was found as p(disj)(h) ~ h(-m) (with m ~
      9-11) for the sufficiently concentrated superspreader solutions, and as
      p(disj)(h) ~ h(-s) (with s ~ 6) for more dilute solutions (in both cases,
      concentrations were above the critical micelle concentration). The non
      superspreaders do not possess any significant disjoining pressure even in the
      films with thicknesses in the 35-100 nm range. The results show that
      gravitational drainage of vertical films is a useful simple tool for measuring
      disjoining pressure.

PMID- 24564486
TI  - Systematic review and meta-analysis on the utility of Interferon-gamma release
      assays for the diagnosis of Mycobacterium tuberculosis infection in children: a
      2013 update.
AB  - BACKGROUND: Previous meta-analyses regarding the performance of interferon-gamma
      release assays (IGRAs) for tuberculosis diagnosis in children yielded contrasting
      results, probably due to different inclusion/exclusion criteria. METHODS: We
      systematically searched PubMed, EMBASE and Cochrane databases and calculated
      pooled estimates of sensitivities and specificities of QuantiFERON-TB Gold In
      Tube (QFT-G-IT), T-SPOT.TB, and tuberculin skin test (TST). Several sub-analysis
      were performed: stratification by background (low income vs. high income
      countries); including only microbiological confirmed TB cases; including only
      studies performing a simultaneous three-way comparison of the three tests, and
      including immunocompromised children. RESULTS: Overall, 31 studies (6183
      children) for QFT-G-IT, 14 studies (2518 children) for T-SPOT.TB and 34 studies
      (6439 children) for TST were included in the analyses. In high income countries
      QFT-G-IT sensitivity was 0.79 (95%IC: 0.75-0.82) considering all the studies,
      0.78 (95%CI:0.70-0.84) including only studies performing a simultaneous three-way
      comparison and 0.86 (95%IC 0.81-0.90) considering only microbiologically
      confirmed studies. In the same analyses T-SPOT.TB sensitivity was 0.67 (95%IC
      0.62-0.73); 0.76 (95%CI: 0.68 to 0.83); and 0.79 (95%IC 0.69-0.87), respectively.
      In low income countries QFT-G-IT pooled sensitivity was significantly lower: 0.57
      (95%IC:0.52-0.61), considering all the studies, and 0.66 (95%IC 0.55-0.76)
      considering only microbiologically confirmed cases; while T-SPOT.TB sensitivity
      was 0.61 (95%IC 0.57-0.65) overall, but reached 0.80 (95%IC 0.73-0.86) in
      microbiologically confirmed cases. In microbiologically confirmed cases TST
      sensitivity was similar: 0.86 (95%IC 0.79-0.91) in high income countries, and
      0.74 (95%IC 0.68-0.80) in low income countries. Higher IGRAs specificity with
      respect to TST was observed in high income countries (97-98% vs. 92%) but not in
      low income countries (85-93% vs. 90%). CONCLUSIONS: Both IGRAs showed no better
      performance than TST in low income countries.

PMID- 24564489
TI  - Understanding the effect of locked nucleic acid and 2'-O-methyl modification on
      the hybridization thermodynamics of a miRNA-mRNA pair in the presence and absence
      of AfPiwi protein.
AB  - miRNAs are some of the key epigenetic regulators of gene expression. They act
      through hybridization with their target mRNA and modulate the level of respective
      proteins via different mechanisms. Various cancer conditions are known to be
      associated with up- and downregulation of the oncogenic and tumor suppressor
      miRNAs, respectively. The levels of aberrantly expressed oncogenic miRNAs can be
      downregulated in different ways. Similarly, restoration of tumor suppressor
      miRNAs to their normal levels can be achieved using miRNA mimics. However, the
      use of miRNA mimics is limited by their reduced biostability and function. We
      have studied the hybridization thermodynamics of the miRNA 26a (11-mer, including
      the seed sequence) guide strand with the mRNA (11-mer) target strand in the
      absence and presence of AfPiwi protein. We have also inserted locked nucleic
      acids (LNAs) and 2'-O-methyl-modified nucleotides into the guide strand, in a
      walk-through manner, to assess their effect on the binding efficiency between
      guide and target RNA. Insertion of LNA and 2'-O-methyl-modified nucleotides into
      the guide strand helped to strengthen the binding affinity irrespective of the
      position of insertion. However, in the presence of AfPiwi protein, these
      modifications reduced the binding affinity to different extents depending on the
      position of insertion. Insertion of a modification leads to an increase in the
      enthalpic contribution with an increased unfavorable entropic contribution, which
      negatively compensates for the higher favorable enthalpy.

PMID- 24564490
TI  - From socialist ideology to cultural heritage: the changing basis of legitimacy in
      the People's Republic of China.
AB  - There has been a shift over the past generation in the moral basis for legitimacy
      of the Chinese state. The socialist state was legitimated by a sinified version
      of Marxism-Leninism, watered with the blood of revolutionary martyrs who fought
      on behalf of the Communist Party to defend the nation from external aggressors.
      However, at many levels of society, the Marxist legitimation is dead. Instead of
      claiming to represent the values of Communist revolutionary struggle in the
      twentieth century, the state is now presenting itself as the carrier and the
      defender of 5000 years of national cultural heritage. This undoubtedly arises
      partly from changes in moral attitude arising from the grass roots and partly
      from government initiatives descending from the top down. There is wide variation
      across China in the intermingling between the bottom-up and top-down moral
      impulses, and this is partially connected with different moral ecologies
      constituted by configurations of state and local political and economic
      institutions throughout China. In this paper, based on case studies from
      fieldwork carried out in several different locations in 2009, the author draws a
      broad map of these variations.

PMID- 24564491
TI  - Eureka-DMA: an easy-to-operate graphical user interface for fast comprehensive
      investigation and analysis of DNA microarray data.
AB  - BACKGROUND: In the past decade, the field of molecular biology has become
      increasingly quantitative; rapid development of new technologies enables
      researchers to investigate and address fundamental issues quickly and in an
      efficient manner which were once impossible. Among these technologies, DNA
      microarray provides methodology for many applications such as gene discovery,
      diseases diagnosis, drug development and toxicological research and it has been
      used increasingly since it first emerged. Multiple tools have been developed to
      interpret the high-throughput data produced by microarrays. However, many times,
      less consideration has been given to the fact that an extensive and effective
      interpretation requires close interplay between the bioinformaticians who analyze
      the data and the biologists who generate it. To bridge this gap and to simplify
      the usability of such tools we developed Eureka-DMA - an easy-to-operate
      graphical user interface that allows bioinformaticians and bench-biologists alike
      to initiate analyses as well as to investigate the data produced by DNA
      microarrays. RESULTS: In this paper, we describe Eureka-DMA, a user-friendly
      software that comprises a set of methods for the interpretation of gene
      expression arrays. Eureka-DMA includes methods for the identification of genes
      with differential expression between conditions; it searches for enriched
      pathways and gene ontology terms and combines them with other relevant features.
      It thus enables the full understanding of the data for following testing as well
      as generating new hypotheses. Here we show two analyses, demonstrating examples
      of how Eureka-DMA can be used and its capability to produce relevant and reliable
      results. CONCLUSIONS: We have integrated several elementary expression analysis
      tools to provide a unified interface for their implementation. Eureka-DMA's
      simple graphical user interface provides effective and efficient framework in
      which the investigator has the full set of tools for the visualization and
      interpretation of the data with the option of exporting the analysis results for
      later use in other platforms. Eureka-DMA is freely available for academic users
      and can be downloaded at http://blue-meduza.org/Eureka-DMA.

PMID- 24564492
TI  - Antibiotics for the treatment of Cholera, Shigella and Cryptosporidium in
      children.
AB  - BACKGROUND: Diarrhea is a major contributor to the burden of morbidity and
      mortality in children; it accounts for a median of 11% of all deaths among
      children aged less than 5 years, amounting to approximately 0.8 million deaths
      per year. Currently there is a dearth of literature exploring the effectiveness
      of antibiotics for diarrhea due to Cholera, Shigella and cryptosporidiosis in
      children. METHODS: We reviewed the literature reporting the effect of antibiotics
      for the treatment of diarrhea due to Cholera, Shigella and Cryptosporidium in
      children under five years. We used a standardized abstraction and grading format
      and performed meta-analyses to determine the effect of the treatment with various
      antibiotics on mortality and rates of clinical and
      bacteriological/parasitological failure. The CHERG Standard Rules were applied to
      determine the final effect of treatment with antibiotics on diarrhea morbidity
      and mortality. RESULTS: For Cholera; the evidence was weak to recommend any
      effect on mortality. For Shigella; there was no data on mortality; either all
      cause or cause specific, hence we used clinical failure rates as a proxy for
      Shigella deaths and propose that treatment of Shigella dysentery with antibiotics
      can result in a 82% reduction in diarrhea mortality due to Shigella. For
      cryptosporidiosis; there was data on all-cause mortality but the evidence was
      weak hence we used clinical failure rates as a proxy for mortality to estimate
      that antimicrobial treatment of diarrhea due to cryptosporidiosis can result in a
      54% reduction in mortality. CONCLUSIONS: There is evidence to recommend
      antibiotic use for reduction of morbidity and mortality due to Cholera, Shigella
      and Cryptosporidium. We recommend that more clinical trials should be conducted
      to evaluate the efficacy and safety of first- and second- line drugs currently in
      use for treatment for diarrhea and dysentery in both developing and developed
      countries.

PMID- 24564493
TI  - Structural insights into mode of actions of novel natural Mycobacterium protein
      tyrosine phosphatase B inhibitors.
AB  - BACKGROUND: Tuberculosis has become a major health problem being the second
      leading cause of death worldwide. Mycobacterium tuberculosis secretes a virulence
      factor, protein tyrosine phosphatase B (mPTPB) in the cytoplasm of host
      macrophage which suppresses its natural innate immune response and helps the
      pathogen survive and proliferate in the phagosome. The present study aims at
      indentifying potent inhibitors of mPTPB by using computational approaches of
      ligand based molecular modeling and docking studies. RESULTS: A 3D QSAR model was
      developed using a set of benzofuran salicylic acid based mPTPB inhibitors with
      experimentally known IC50 values. The model was generated using the statistical
      method of principle component regression analysis in combination with step wise
      forward variable selection algorithm. It was observed that steric and hydrophobic
      descriptors positively contribute towards the inhibitory activity of the ligands.
      The developed model had a robust internal as well as external predictive power as
      indicated by the q(2) value of 0.8920 and predicted r(2) value of 0.8006
      respectively. Hence, the generated model was used to screen a large set of
      naturally occurring chemical compounds and predict their biological activity to
      identify more potent natural compounds targeting mPTPB. The two top potential
      hits (with pIC50 value of 1.459 and 1.677 respectively) had a similar interaction
      pattern as that of the most potent compound (pIC50 = 1.42) of the congeneric
      series. CONCLUSION: The contour plot provided a better understanding of the
      relationship between structural features of substituted benzofuran salicylic acid
      derivatives and their activities which would facilitate design of novel mPTPB
      inhibitors. The QSAR modeling was used to obtain an equation, correlating the
      important steric and hydrophobic descriptors with the pIC50 value. Thus, we
      report two natural compounds of inhibitory nature active against mPTPB enzyme of
      Mycobacterium tuberculosis. These inhibitors have the potential to evolve as lead
      molecules in the development of drugs for the treatment of tuberculosis.

PMID- 24564494
TI  - Silicate esters of paclitaxel and docetaxel: synthesis, hydrophobicity,
      hydrolytic stability, cytotoxicity, and prodrug potential.
AB  - We report here the synthesis and selected properties of various silicate ester
      derivatives (tetraalkoxysilanes) of the taxanes paclitaxel (PTX) and docetaxel
      (DTX) [i.e., PTX-OSi(OR)3 and DTX-OSi(OR)3]. Both the hydrophobicity and
      hydrolytic lability of these silicates can be (independently) controlled by
      choice of the alkyl group (R). The synthesis, structural characterization,
      hydrolytic reactivity, and in vitro cytotoxicity against the MDA-MB-231 breast
      cancer cell line of most of these derivatives are described. We envision that the
      greater hydrophobicity of these silicates (vis-a-vis PTX or DTX itself) should be
      advantageous from the perspective of preparation of stable aqueous dispersions of
      amphiphilic block-copolymer-based nanoparticle formulations. 

PMID- 24564497
TI  - Assessing the influence of secondary organic versus primary carbonaceous aerosols
      on long-range atmospheric polycyclic aromatic hydrocarbon transport.
AB  - We use the chemical transport model GEOS-Chem to evaluate the hypothesis that
      atmospheric polycyclic aromatic hydrocarbons (PAHs) are trapped in secondary
      organic aerosol (SOA) as it forms. We test the ability of three different
      partitioning configurations within the model to reproduce observed total
      concentrations in the midlatitudes and the Arctic as well as midlatitude gas
      particle phase distributions. The configurations tested are (1) the GEOS-Chem
      default configuration, which uses instantaneous equilibrium partitioning to
      divide PAHs among the gas phase, a primary organic matter (OM) phase
      (absorptive), and a black carbon (BC) phase (adsorptive), (2) an SOA
      configuration in which PAHs are trapped in SOA when emitted and slowly evaporate
      from SOA thereafter, and (3) a configuration in which PAHs are trapped in primary
      OM/BC upon emission and subsequently slowly evaporate. We also test the influence
      of changing the fraction of PAHs available for particle-phase oxidation. Trapping
      PAHs in SOA particles upon formation and protecting against particle-phase
      oxidation (2) better simulates observed remote concentrations compared to our
      default configuration (1). However, simulating adsorptive partitioning to BC is
      required to reproduce the magnitude and seasonal pattern of gas-particle phase
      distributions. Thus, the last configuration (3) results in the best agreement
      between observed and simulated concentration/phase distribution data. The
      importance of BC rather than SOA to PAH transport is consistent with strong
      observational evidence that PAHs and BC are coemitted. 

PMID- 24564495
TI  - The effects of myocilin expression on functionally relevant trabecular meshwork
      genes: a mini-review.
AB  - Myocilin is a secreted glaucoma-associated protein, specifically induced by
      dexamethasone in human trabecular meshwork cells, where it was discovered.
      Myocilin is expressed in several tissues of the body, but it causes disease only
      in the eye. The protein contains two domains: an N-terminal region with
      significant homologies to nonmuscle myosin, and a C-terminal region, which is
      similar to the olfactomedin proteins. Forty percent of myocilin undergoes an
      intracellular endoproteolytic cleavage by calpain II, a calcium-dependent
      cysteine protease, which releases the 2 domains. The protein is known to interact
      with intracellular and extracellular matrix proteins, and some is released into
      the extracellular space associated with exosomes. Myocilin mutations are linked
      to glaucoma and induce elevated intraocular pressure. Most of the glaucoma
      causative mutations map to the olfactomedin domain, which appears to be a
      critical domain for the function of the protein. Myocilin mutants are misfolded,
      aggregate in the endoplasmic reticulum, and are not secreted. Overexpression of
      myocilin and of its mutants in primary human trabecular meshwork cells triggers
      changes in the expression of numerous genes, many of which have been known to be
      involved in mechanisms important for the physiology and pathology of the tissue.
      Here we review recent studies from our laboratory and those of others that deal
      with trabecular meshwork genes, which are altered by the overexpression of wild
      type and glaucoma-causative mutant myocilin genes.

PMID- 24564499
TI  - Select and treat at laparoscopy and dye test improves the spontaneous pregnancy.
AB  - Infertility affects 1 in 7 couples in the UK. Tubal patency tests are an
      important part of infertility investigations. We conducted this observational
      study to determine the interval between a laparoscopy and dye test and
      spontaneous conception in women with unexplained infertility and minimal to mild
      endometriosis and pelvic adhesions treated during the procedure. The clinical
      records of 432 women coded as having had a laparoscopy and dye test or
      laparoscopy and tubal patency test between April 2007 and March 2010 were
      retrieved from a computerised theatre database. Pregnancies were identified
      through a computerised maternity booking system. Spontaneous pregnancies were
      recorded in 162 women following surgery (37.5%). There was a significant
      difference in conception rates between women with unexplained infertility and
      those with minor abnormalities treated at the time of diagnosis (43% vs. 58%, p =
      0.019). Eighty percent of women who conceived spontaneously achieved their
      pregnancy within 18 months of surgery. A high proportion of women with
      unexplained infertility or minor abnormalities treated at the time of a
      laparoscopy and dye test conceived spontaneously within 12 months.

PMID- 24564496
TI  - RMaNI: Regulatory Module Network Inference framework.
AB  - BACKGROUND: Cell survival and development are orchestrated by complex
      interlocking programs of gene activation and repression. Understanding how this
      gene regulatory network (GRN) functions in normal states, and is altered in
      cancers subtypes, offers fundamental insight into oncogenesis and disease
      progression, and holds great promise for guiding clinical decisions. Inferring a
      GRN from empirical microarray gene expression data is a challenging task in
      cancer systems biology. In recent years, module-based approaches for GRN
      inference have been proposed to address this challenge. Despite the demonstrated
      success of module-based approaches in uncovering biologically meaningful
      regulatory interactions, their application remains limited a single condition,
      without supporting the comparison of multiple disease subtypes/conditions. Also,
      their use remains unnecessarily restricted to computational biologists, as
      accurate inference of modules and their regulators requires integration of
      diverse tools and heterogeneous data sources, which in turn requires scripting
      skills, data infrastructure and powerful computational facilities. New analytical
      frameworks are required to make module-based GRN inference approach more
      generally useful to the research community. RESULTS: We present the RMaNI
      (Regulatory Module Network Inference) framework, which supports cancer subtype
      specific or condition specific GRN inference and differential network analysis.
      It combines both transcriptomic as well as genomic data sources, and integrates
      heterogeneous knowledge resources and a set of complementary bioinformatic
      methods for automated inference of modules, their condition specific regulators
      and facilitates downstream network analyses and data visualization. To
      demonstrate its utility, we applied RMaNI to a hepatocellular microarray data
      containing normal and three disease conditions. We demonstrate that how RMaNI can
      be employed to understand the genetic architecture underlying three disease
      conditions. RMaNI is freely available at
      http://inspect.braembl.org.au/bi/inspect/rmani CONCLUSION: RMaNI makes available
      a workflow with comprehensive set of tools that would otherwise be challenging
      for non-expert users to install and apply. The framework presented in this paper
      is flexible and can be easily extended to analyse any dataset with multiple
      disease conditions.

PMID- 24564500
TI  - Automatic classification of protein structures using low-dimensional structure
      space mappings.
AB  - BACKGROUND: Protein function is closely intertwined with protein structure.
      Discovery of meaningful structure-function relationships is of utmost importance
      in protein biochemistry and has led to creation of high-quality, manually curated
      classification databases, such as the gold-standard SCOP (Structural
      Classification of Proteins) database. The SCOP database and its counterparts such
      as CATH provide a detailed and comprehensive description of the structural and
      evolutionary relationships of the proteins of known structure and are widely
      employed in structural and computational biology. Since manual classification is
      both subjective and highly laborious, automated classification of novel
      structures is increasingly an active area of research. The design of methods for
      automated structure classification has been rendered even more important since
      the recent past, due to the explosion in number of solved structures arising out
      of various structural biology initiatives. In this paper we propose an approach
      to the problem of structure classification based on creating and tessellating low
      dimensional maps of the protein structure space (MPSS). Given a set of protein
      structures, an MPSS is a low dimensional embedding of structural similarity-based
      distances between the molecules. In an MPSS, a group of proteins (such as all the
      proteins in the PDB or sub-samplings thereof) under consideration are represented
      as point clouds and structural relatedness maps to spatial adjacency of the
      points. In this paper we present methods and results that show that MPSS can be
      used to create tessellations of the protein space comparable to the clade systems
      within SCOP. Though we have used SCOP as the gold standard, the proposed approach
      is equally applicable for other structural classifications. METHODS: In the
      proposed approach, we first construct MPSS using pairwise alignment distances
      obtained from four established structure alignment algorithms (CE, Dali, FATCAT
      and MATT). The low dimensional embeddings are next computed using an embedding
      technique called multidimensional scaling (MDS). Next, by using the remotely
      homologous Superfamily and Fold levels of the hierarchical SCOP database, a
      distance threshold is determined to relate adjacency in the low dimensional map
      to functional relationships. In our approach, the optimal threshold is determined
      as the value that maximizes the total true classification rate vis-a-vis the SCOP
      classification. We also show that determining such a threshold is often
      straightforward, once the structural relationships are represented using MPSS.
      RESULTS AND CONCLUSION: We demonstrate that MPSS constitute highly accurate
      representations of protein fold space and enable automatic classification of SCOP
      Superfamily and Fold-level relationships. The results from our automatic
      classification approach are remarkably similar to those found in the distantly
      homologous Superfamily level and the quite remotely homologous Fold levels of
      SCOP. The significance of our results are underlined by the fact that most
      automated methods developed thus far have only managed to match the closest
      homology Family level of the SCOP hierarchy and tend to differ considerably at
      the Superfamily and Fold levels. Furthermore, our research demonstrates that
      projection into a low-dimensional space using MDS constitutes a superior
      noisereducing transformation of pairwise distances than do the variety of
      probability- and alignment-length-based transformations currently used by
      structure alignment algorithms.

PMID- 24564503
TI  - Typical smokestack leak sign in a case of Vogt-Koyanagi-Harada disease.

PMID- 24564501
TI  - Quantitative proteomics by SWATH-MS reveals altered expression of nucleic acid
      binding and regulatory proteins in HIV-1-infected macrophages.
AB  - Human immunodeficiency virus type 1 (HIV-1) infection remains a worldwide
      epidemic, and innovative therapies to combat the virus are needed. Developing a
      host-oriented antiviral strategy capable of targeting the biomolecules that are
      directly or indirectly required for viral replication may provide advantages over
      traditional virus-centric approaches. We used quantitative proteomics by SWATH-MS
      in conjunction with bioinformatic analyses to identify host proteins, with an
      emphasis on nucleic acid binding and regulatory proteins, which could serve as
      candidates in the development of host-oriented antiretroviral strategies. Using
      SWATH-MS, we identified and quantified the expression of 3608 proteins in
      uninfected and HIV-1-infected monocyte-derived macrophages. Of these 3608
      proteins, 420 were significantly altered upon HIV-1 infection. Bioinformatic
      analyses revealed functional enrichment for RNA binding and processing as well as
      transcription regulation. Our findings highlight a novel subset of proteins and
      processes that are involved in the host response to HIV-1 infection. In addition,
      we provide an original and transparent methodology for the analysis of label-free
      quantitative proteomics data generated by SWATH-MS that can be readily adapted to
      other biological systems. 

PMID- 24564504
TI  - Uniform, high aspect ratio fiber-like micelles and block co-micelles with a
      crystalline pi-conjugated polythiophene core by self-seeding.
AB  - Monodisperse fiber-like micelles with a crystalline pi-conjugated polythiophene
      core with lengths up to ca. 700 nm were successfully prepared from the diblock
      copolymer poly(3-hexylthiophene)-block-polystyrene using a one-dimensional self
      seeding technique. Addition of a polythiophene block copolymer with a different
      corona-forming block to the resulting nanofibers led to the formation of
      segmented B-A-B triblock co-micelles by crystallization-driven seeded growth. The
      key to these advances appears to be the formation of a relatively defect-free
      crystalline micelle core under the self-seeding conditions. 

PMID- 24564502
TI  - Identification of fibrillin 1 gene mutations in patients with bicuspid aortic
      valve (BAV) without Marfan syndrome.
AB  - BACKGROUND: Bicuspid aortic valve (BAV) is the most frequent congenital heart
      disease with frequent involvement in thoracic aortic dilatation, aneurysm and
      dissection. Although BAV and Marfan syndrome (MFS) share some clinical features,
      and some MFS patients with BAV display mutations in FBN1, the gene encoding
      fibrillin-1, the genetic background of isolated BAV is poorly defined. METHODS:
      Ten consecutive BAV patients [8 men, age range 24-42 years] without MFS were
      clinically characterized. BAV phenotype and function, together with evaluation of
      aortic morphology, were comprehensively assessed by Doppler echocardiography.
      Direct sequencing of each FBN1 exon with flanking intron sequences was performed
      on eight patients. RESULTS: We detected three FBN1 mutations in two patients
      (aged 24 and 25 years) displaying aortic root aneurysm >=50 mm and moderate
      aortic regurgitation. In particular, one patient had two mutations (p.Arg2726Trp
      and p.Arg636Gly) one of which has been previously associated with variable
      Marfanoid phenotypes. The other patient showed a pArg529Gln substitution reported
      to be associated with an incomplete MFS phenotype. CONCLUSIONS: The present
      findings enlarge the clinical spectrum of isolated BAV to include patients with
      BAV without MFS who have involvement of FBN1 gene. These results underscore the
      importance of accurate phenotyping of BAV aortopathy and of clinical
      characterization of BAV patients, including investigation of systemic connective
      tissue manifestations and genetic testing.

PMID- 24564505
TI  - A complete gear system in N-benzoyl-carbazole derivatives.
AB  - 2',6'-Disubstituted N-benzoylated carbazole derivatives were found to exhibit
      atropisomerism. The bulky substituents restricted rotation about the N-C7' and
      C7'-C1' bonds to separate four atropisomers, in which rotation about the C7'-C1'
      bond was in perfect concert with rotation about the N-C7' bond. Complete geared
      rotation without slippage at 37  degrees C for 7 days was observed for the first
      time. Conformational analysis clarified the preference for the gear system over
      other internal conversion pathways. 

PMID- 24564506
TI  - EBV and other viruses as triggers of tertiary lymphoid structures in primary
      Sjogren's syndrome.
AB  - Sjogren's syndrome (SS) is an autoimmune disease that targets salivary (SG) and
      lachrymal glands, leading to exocrine dysfunction. Several viruses have been
      associated with SS, although the role of persistent viral infections in
      triggering and/or perpetuating the disease is still a matter of controversy.
      Together with exocrine dysfunction, SS is characterised by the production of
      autoantibodies and the presence of lymphomonocytic periductal aggregates in the
      SG, which in 30/40% of the patients display features of tertiary lymphoid
      structures (TLS) supporting an ectopic germinal centre response. Here we first
      review i) the relevance of TLS in SS and ii) the evidence in support of a role
      for viruses in SS insurgence and/or persistence; next, iii) we review recent data
      which links viral infection with TLS formation in the SG and suggests that viral
      host interactions within TLS favour breach of tolerance and development of
      autoimmunity in SS. 

PMID- 24564507
TI  - B-cell hyperactivity in primary Sjogren's syndrome.
AB  - Primary Sjogren's syndrome (pSS) is characterized by mononuclear inflammatory
      infiltrates and IgG plasma cells in salivary and lacrimal glands which lead to
      irreversible destruction of the glandular tissue and is accompanied by sensation
      of dryness of mouth and eyes. B cells play a central role in the
      immunopathogenesis and exhibit signs of hyperactivity. Hyperactivity of B cells
      is the consequence of the coordinated and integrated action of stimulation of the
      B-cell receptor, CD40 and toll-like receptors in the presence of appropriate
      cytokines. As discussed, overexpression of type I IFN and BAFF on one hand and IL
      6 and IL-21 on the other hand are critically involved in the enhanced plasma cell
      formation in pSS patients. Hyperactivity of B cells results in secretion of
      autoantibodies and production of various cytokines. These insights in the role of
      B cells in the pathogenetic process of pSS offer ample targets for successful
      therapeutical intervention in pSS. 

PMID- 24564508
TI  - What causes dryness in Sjogren's syndrome patients and how can it be targeted?
AB  - Concepts regarding what causes dryness in Sjogren's syndrome have evolved over
      the past decade. Inflammation in the lacrimal functional unit contributes to
      development of dry eye by causing dysfunction and even death of tear secreting
      epithelium in the lacrimal gland and conjunctiva that alters tear composition and
      stability. Disease-relevant inflammatory mediators have been identified and
      therapies targeting these mediators are beginning to emerge. 

PMID- 24564509
TI  - Stagnant women's health issues.

PMID- 24564511
TI  - Structure-based energetics of mRNA decoding on the ribosome.
AB  - The origin of high fidelity in bacterial protein synthesis on the ribosome
      remains a fundamental unsolved problem despite available three-dimensional
      structures of different stages of the translation process. However, these
      structures open up the possibility of directly computing the energetics of tRNA
      selection that is required for an authentic understanding of fidelity in
      decoding. Here, we report extensive computer simulations that allow us to
      quantitatively calculate tRNA discrimination and uncover the energetics
      underlying accuracy in code translation. We show that the tRNA-mRNA interaction
      energetics varies drastically along the path from initial selection to peptide
      bond formation. While the selection process is obviously controlled by kinetics,
      the underlying thermodynamics explains the origin of the high degree of accuracy.
      The existence of both low- and high-selectivity states provides an efficient
      mechanism for initial selection and proofreading that does not require codon
      dependent long-range structural signaling within the ribosome. It is instead the
      distinctly unequal population of the high-selectivity states for cognate and
      noncognate substrates that is the key discriminatory factor. The simulations
      reveal the essential roles played both by the 30S subunit conformational switch
      and by the common tRNA modification at position 37 in amplifying the accuracy.

PMID- 24564512
TI  - Molecular complexity from polyunsaturated substrates: the gold catalysis
      approach.
AB  - Over the last two decades, electrophilic catalysis relying on platinum(II),
      gold(I), and gold(III) salts has emerged as a remarkable synthetic methodology.
      Chemists have discovered a large variety of organic transformations that convert
      a great assortment of highly functionalized precursors into valuable final
      products. In many cases, these methodologies offer unique features, allowing
      access to unprecedented molecular architectures. Due to the mild reaction
      conditions and high function compatibility, scientists have successfully
      developed applications in total synthesis of natural products, as well as in
      asymmetric catalysis. In addition, all these developments have been accompanied
      by the invention of well-tailored catalysts, so that a palette of different
      electrophilic agents is now commercially available or readily synthesized at the
      bench. In some respects, researchers' interests in developing homogeneous gold
      catalysis can be compared with the Californian gold rush of the 19th century. It
      has attracted into its fervor thousands of scientists, providing a huge number of
      versatile and important reports. More notably, it is clear that the contribution
      to the art of organic synthesis is very valuable, though the quest is not over
      yet. Because they rely on the intervention of previously unknown types of
      intermediates, new retrosynthetic disconnections are now possible. In this
      Account, we discuss our efforts on the use of readily available polyunsaturated
      precursors, such as enynes, dienynes, allenynes, and allenenes to give access to
      highly original polycyclic structures in a single operation. These
      transformations transit via previously undescribed intermediates A, B, D, F, and
      H that will be encountered later on. All these intermediates have been determined
      by both ourselves and others by DFT calculations and in some cases have been
      confirmed on the basis of experimental data. In addition, dual gold activation
      can be at work in some of these transformations, for instance, from E to F.
      Strikingly, we have found propargyl acetates to be particularly productive
      precursors. In a preliminary step upon electrophilic activation (complex I), they
      can lead to oxonium J or a vinylcarbenoid species K after 1,2-migration or
      complexed allenylester M from a formal 1,3-migration. All of them can serve as
      versatile entries for multievent processes. The propargyl cycle, sometimes called
      the golden carousel, involves species I-N), which lie in a close equilibrium. The
      control of this merry-go-round and its offshoots depends on the energy barriers
      associated with the subsequent reactions of these intermediates. We illustrate
      these themes in this Account, focusing on the intriguing characteristics of gold
      catalysis. 

PMID- 24564510
TI  - Vaccines for the prevention of diarrhea due to cholera, shigella, ETEC and
      rotavirus.
AB  - BACKGROUND: Diarrhea is a leading cause of mortality in children under 5 years
      along with its long-term impact on growth and cognitive development. Despite
      advances in the understanding of diarrheal disorders and management strategies,
      globally nearly 750,000 children die annually as a consequence of diarrhea.
      METHODS: We conducted a systematic review of the efficacy and effectiveness
      studies. We used a standardized abstraction and grading format and performed meta
      analyses for all outcomes. The estimated effect of cholera, shigella,
      Enterotoxigenic Escherichia coli (ETEC) and rotavirus vaccines was determined by
      applying the standard Child Health Epidemiology Reference Group (CHERG) rules.
      RESULTS: A total of 24 papers were selected and analyzed for all the four
      vaccines. Based on the evidence, we propose a 74% mortality reduction in
      rotavirus specific mortality, 52% reduction in cholera incidence due to their
      respective vaccines. We did not find sufficient evidence and a suitable outcome
      to project mortality reductions for cholera, ETEC and shigella in children under
      5 years. CONCLUSION: Vaccines for rotavirus and cholera have the potential to
      reduce diarrhea morbidity and mortality burden. But there is no substantial
      evidence of efficacy for ETEC and shigella vaccines, although several promising
      vaccine concepts are moving from the development and testing pipeline towards
      efficacy and Phase 3 trials.

PMID- 24564513
TI  - Psychophysiological detection of concealed information shared by groups: an
      empirical study of the searching CIT.
AB  - This study focused on the application of the Concealed Information Test (CIT) to
      situations in which the crime-related information is shared by a group of
      suspects but is not available to the investigators (a method known as the
      "searching CIT," or SCIT). Twenty-two groups, each comprising 4 to 7 participants
      (115 in total), planned 1 of 2 mock crimes (kidnapping or bank robbery). While
      planning the crime, each group decided on 5 crime-related critical items (e.g.,
      the city in which the bank was located). Each critical item was chosen from a
      predefined set of 4 alternatives. At a second stage, the SCIT was administered
      individually and each participant was tested on the 2 crimes-the actual planned
      crime, in which the participant was "guilty," and the unplanned crime, in which
      the participant was "innocent." Two algorithms, adopted from Breska, Ben-Shakhar,
      and Gronau (2012), were applied to detect the critical items and to differentiate
      between "guilty" and "innocent" participants. Findings revealed that
      differentiation efficiency based on electrodermal and respiration measures was
      identical to that obtained with the standard CIT when applied to large groups,
      but lower, although significantly greater than chance, when applied to
      differentiate between small groups.

PMID- 24564514
TI  - Towards sequence-based prediction of mutation-induced stability changes in unseen
      non-homologous proteins.
AB  - BACKGROUND: Reliable prediction of stability changes induced by a single amino
      acid substitution is an important aspect of computational protein design. Several
      machine learning methods capable of predicting stability changes from the protein
      sequence alone have been introduced. Prediction performance of these methods is
      evaluated on mutations unseen during training. Nevertheless, different mutations
      of the same protein, and even the same residue, as encountered during training
      are commonly used for evaluation. We argue that a faithful evaluation can be
      achieved only when a method is tested on previously unseen proteins with low
      sequence similarity to the training set. RESULTS: We provided experimental
      evidence of the limitations of the evaluation commonly used for assessing the
      prediction performance. Furthermore, we demonstrated that the prediction of
      stability changes in previously unseen non-homologous proteins is a challenging
      task for currently available methods. To improve the prediction performance of
      our previously proposed method, we identified features which led to over-fitting
      and further extended the model with new features. The new method employs
      Evolutionary And Structural Encodings with Amino Acid parameters (EASE-AA).
      Evaluated with an independent test set of more than 600 mutations, EASE-AA
      yielded a Matthews correlation coefficient of 0.36 and was able to classify
      correctly 66% of the stabilising and 74% of the destabilising mutations. For real
      value prediction, EASE-AA achieved the correlation of predicted and
      experimentally measured stability changes of 0.51. CONCLUSIONS: Commonly adopted
      evaluation with mutations in the same protein, and even the same residue,
      randomly divided between the training and test sets lead to an overestimation of
      prediction performance. Therefore, stability changes prediction methods should be
      evaluated only on mutations in previously unseen non-homologous proteins. Under
      such an evaluation, EASE-AA predicts stability changes more reliably than
      currently available methods.

PMID- 24564515
TI  - Physicochemical aspects of lipase B from Candida antarctica in bicontinuous
      microemulsions.
AB  - Biotechnology involves applying enzymes in organic synthesis to convert non
      natural substrates into enantiomerically pure products under mild reaction
      conditions. Non-natural substrates are often lipophilic molecules that can hardly
      be accessed and converted by enzymes in their natural aqueous environment.
      Bicontinuous microemulsions provide a spongelike nanostructure with a large
      interfacial area between aqueous and oil domains, which makes them valuable
      alternative reaction media. In the present study, we introduced lipase B from
      Candida antarctica into a bicontinuous microemulsion of composition H2O/NaCl-n
      octane-pentaethylene glycol monodecylether (C10E5). Phase behavior, partitioning
      studies, and pulsed-field-gradient NMR measurements revealed that the lipase is
      mostly adsorbed at the microemulsions interface. Phase diagrams showed a maximum
      in efficiency with increasing amount of lipase added to the water phase of the
      microemulsion. It was observed that the ratio between the mass of lipase that is
      introduced into the system and the mass of lipase that is located at the
      interface stays constant. Self-diffusion coefficients of all components showed
      that the presence of the lipase is not influencing the bicontinuity of the
      microemulsion.

PMID- 24564516
TI  - Quantitative synteny scoring improves homology inference and partitioning of gene
      families.
AB  - BACKGROUND: Clustering sequences into families has long been an important step in
      characterization of genes and proteins. There are many algorithms developed for
      this purpose, most of which are based on either direct similarity between gene
      pairs or some sort of network structure, where weights on edges of constructed
      graphs are based on similarity. However, conserved synteny is an important signal
      that can help distinguish homology and it has not been utilized to its fullest
      potential. RESULTS: Here, we present GenFamClust, a pipeline that combines the
      network properties of sequence similarity and synteny to assess homology
      relationship and merge known homologs into groups of gene families. GenFamClust
      identifies homologs in a more informed and accurate manner as compared to
      similarity based approaches. We tested our method against the Neighborhood
      Correlation method on two diverse datasets consisting of fully sequenced genomes
      of eukaryotes and synthetic data. CONCLUSIONS: The results obtained from both
      datasets confirm that synteny helps determine homology and GenFamClust improves
      on Neighborhood Correlation method. The accuracy as well as the definition of
      synteny scores is the most valuable contribution of GenFamClust.

PMID- 24564517
TI  - First finding of Ostreopsis cf. ovata toxins in marine aerosols.
AB  - Since the late 1990s, a respiratory syndrome has been repetitively observed in
      humans concomitant with Ostreopsis spp. blooms (mainly O. cf. ovata) in the
      Mediterranean area. Previous studies have demonstrated that O. cf. ovata produces
      analogues of palytoxin (ovatoxins and a putative palytoxin), one of the most
      potent marine toxins. On the basis of the observed association between O. cf.
      ovata blooms, respiratory illness in people, and detection of palytoxin complex
      in algal samples, toxic aerosols, containing Ostreopsis cells and/or the toxins
      they produce, were postulated to be the cause of human illness. A small scale
      monitoring study of marine aerosol carried out along the Tuscan coasts (Italy) in
      2009 and 2010 is reported. Aerosols were collected concomitantly with O. cf.
      ovata blooms, and they were analyzed by both PCR assays and LC-HRMS. The results,
      besides confirming the presence of O. cf. ovata cells, demonstrated for the first
      time the occurrence of ovatoxins in the aerosol at levels of 2.4 pg of ovatoxins
      per liter of air. Given the lack of toxicological data on palytoxins by
      inhalation exposure, our results are only a first step toward a more
      comprehensive understanding of the Ostreopsis-related respiratory syndrome. 

PMID- 24564518
TI  - MetaID: a novel method for identification and quantification of metagenomic
      samples.
AB  - BACKGROUND: Advances in next-generation sequencing (NGS) technology has provided
      us with an opportunity to analyze and evaluate the rich microbial communities
      present in all natural environments. The shorter reads obtained from the shortgun
      technology has paved the way for determining the taxonomic profile of a community
      by simply aligning the reads against the available reference genomes. While
      several computational methods are available for taxonomic profiling at the genus-
      and species-level, none of these methods are effective at the strain-level
      identification due to the increasing difficulty in detecting variation at that
      level. Here, we present MetaID, an alignment-free n-gram based approach that can
      accurately identify microorganisms at the strain level and estimate the abundance
      of each organism in a sample, given a metagenomic sequencing dataset. RESULTS:
      MetaID is an n-gram based method that calculates the profile of unique and common
      n-grams from the dataset of 2,031 prokaryotic genomes and assigns weights to each
      n-gram using a scoring function. This scoring function assigns higher weightage
      to the n-grams that appear in fewer genomes and vice versa; thus, allows for
      effective use of both unique and common n-grams for species identification. Our
      10-fold cross-validation results on a simulated dataset show a remarkable
      accuracy of 99.7% at the strain-level identification of the organisms in gut
      microbiome. We also demonstrated that our model shows impressive performance even
      by using only 25% or 50% of the genome sequences for modeling. In addition to
      identification of the species, our method can also estimate the relative
      abundance of each species in the simulated metagenomic samples. The generic
      approach employed in this method can be applied for accurate identification of a
      wide variety of microbial species (viruses, prokaryotes and eukaryotes) present
      in any environmental sample. CONCLUSIONS: The proposed scoring function and
      approach is able to accurately identify and estimate the entire taxa in any
      metagenomic community. The weights assigned to the common n-grams by our scoring
      function are precisely calibrated to match the reads up to the strain level. Our
      multipronged validation tests demonstrate that MetaID is sufficiently robust to
      accurately identify and estimate the abundance of each taxon in any natural
      environment even when using incomplete or partially sequenced genomes.

PMID- 24564519
TI  - Body mass index change in autism spectrum disorders: comparison of treatment with
      risperidone and aripiprazole.
AB  - OBJECTIVE: The purpose of this study was to assess change in body mass index
      (BMI) and age- and gender-adjusted BMI Z-score in subjects ages 2-20 years with
      autism spectrum disorders (ASD), who were treated longitudinally with risperidone
      or aripiprazole at a tertiary care ASD clinic. METHOD: As part of a larger
      project involving longitudinal drug treatment data in ASD, detailed demographic
      and treatment data were collected for 142 subjects ages 2-20 years who had been
      started on risperidone or aripiprazole for treatment of irritability. Mean age at
      start of treatment, treatment duration, final Clinical Global Impressions
      Improvement Scale score, BMI change per year of treatment, and BMI Z-score change
      per year of treatment (primary outcome measure) were calculated for each drug
      treatment group. Group means were compared using t tests and Wilcoxon rank sum
      tests. RESULTS: There was a statistically significant BMI and BMI Z-score
      increase in the risperidone and aripiprazole treatment groups individually. No
      statistically significant difference between the two treatment groups was noted
      in mean BMI change per year of treatment or BMI Z-score change per year of
      treatment. CONCLUSIONS: In our review of long-term naturalistic treatment of
      irritability using risperidone versus aripiprazole in persons with ASD, a
      significant increase in both BMI and age- and gender-adjusted BMI Z-score was
      noted for each treatment group. No significant difference in BMI or BMI Z-score
      change was noted when the two treatment groups were compared. We conclude that in
      our patient population at a tertiary care ASD clinic, the effects of risperidone
      and aripiprazole on body weight gain in naturalistic long-term treatment are no
      different.

PMID- 24564521
TI  - Inhibitory effect of water on the oxygen reduction catalyzed by cobalt(II)
      tetraphenylporphyrin.
AB  - Stopped-flow kinetic measurements, UV-vis spectroscopy, rotating disk
      voltammetry, and quantum chemical calculations are used to clarify the role of
      water in the homogeneous two-electron reduction of O2 to H2O2 in 1,2
      dichloroethane (DCE) using ferrocene (Fc) as an electron donor,
      tetrakis(pentafluorophenyl)boric acid (HTB) as a proton donor, and [5,10,15,20
      tetraphenyl-21H,23H-porphine]cobalt(II) (Co(II)TTP) as a catalyst. Kinetic
      analysis suggests that the reaction is controlled by the intramolecular proton
      coupled electron transfer to the O2 molecule coordinated to the metal center
      producing the O2H(*) radical. This rate-determining step is common to both the O2
      reduction by Fc catalyzed by Co(II)TPP and the O2 reduction by Co(II)TPP itself.
      Experimental data point to the competitive coordination of water to the metal
      center leading to a strong inhibition of the catalytic reaction. In agreement
      with this finding, quantum chemical calculations indicate that water is bound to
      the metal center much more strongly than triplet O2. A similar effect is
      demonstrated also for the O2 reduction catalyzed by the porphyrin free base
      (H2TPP), though its rate is lower by 2 orders of magnitude. 

PMID- 24564520
TI  - Financial incentives and coverage of child health interventions: a systematic
      review and meta-analysis.
AB  - BACKGROUND: Financial incentives are widely used strategies to alleviate poverty,
      foster development, and improve health. Cash transfer programs, microcredit, user
      fee removal policies and voucher schemes that provide direct or indirect monetary
      incentives to households have been used for decades in Latin America, Sub-Saharan
      Africa, and more recently in Southeast Asia. Until now, no systematic review of
      the impact of financial incentives on coverage and uptake of health interventions
      targeting children under 5 years of age has been conducted. The objective of this
      review is to provide estimates on the effect of six types of financial incentive
      programs: (i) Unconditional cash transfers (CT), (ii) Conditional cash transfers
      (CCT), (iii) Microcredit (MC), (iv) Conditional Microcredit (CMC), (v) Voucher
      schemes (VS) and (vi) User fee removal (UFR) on the uptake and coverage of health
      interventions targeting children under the age of five years. METHODS: We
      conducted systematic searches of a series of databases until September 1st, 2012,
      to identify relevant studies reporting on the impact of financial incentives on
      coverage of health interventions and behaviors targeting children under 5 years
      of age. The quality of the studies was assessed using the CHERG criteria. Meta
      analyses were undertaken to estimate the effect when multiple studies meeting our
      inclusion criteria were available. RESULTS: Our searches resulted in 1671 titles
      identified 25 studies reporting on the impact of financial incentive programs on
      5 groups of coverage indicators: breastfeeding practices (breastfeeding
      incidence, proportion of children receiving colostrum and early initiation of
      breastfeeding, exclusive breastfeeding for six months and duration of
      breastfeeding); vaccination (coverage of full immunization, partial immunization
      and specific antigens); health care use (seeking healthcare when child was ill,
      visits to health facilities for preventive reasons, visits to health facilities
      for any reason, visits for health check-up including growth control); management
      of diarrhoeal disease (ORS use during diarrhea episode, continued feeding during
      diarrhea, healthcare during diarrhea episode) and other preventive health
      interventions (iron supplementation, vitamin A, zinc supplementation, preventive
      deworming). The quality of evidence on the effect of financial incentives on
      breastfeeding practices was low but seems to indicate a potential positive impact
      on receiving colostrum, early initiation of breastfeeding, exclusive
      breastfeeding and mean duration of exclusive breastfeeding. There is no effect of
      financial incentives on immunization coverage although there was moderate quality
      evidence of conditional cash transfers leading to a small but non-significant
      increase in coverage of age-appropriate immunization. There was low quality
      evidence of impact of CCT on healthcare use by children under age 5 (Risk
      difference: 0.14 [95%CI: 0.03; 0.26]) as well as low quality evidence of an
      effect of user fee removal on use of curative health services (RD=0.62 [0.41;
      0.82]). CONCLUSIONS: Financial incentives may have potential to promote increased
      coverage of several important child health interventions, but the quality of
      evidence available is low. The more pronounced effects seem to be achieved by
      programs that directly removed user fees for access to health services. Some
      indication of effect were also observed for programs that conditioned financial
      incentives on participation in health education and attendance to health care
      visits. This finding suggest that the measured effect may be less a consequence
      of the financial incentive and more due to conditionalities addressing important
      informational barriers.

PMID- 24564522
TI  - Incorporating substrate sequence motifs and spatial amino acid composition to
      identify kinase-specific phosphorylation sites on protein three-dimensional
      structures.
AB  - BACKGROUND: Protein phosphorylation catalyzed by kinases plays crucial regulatory
      roles in cellular processes. Given the high-throughput mass spectrometry-based
      experiments, the desire to annotate the catalytic kinases for in vivo
      phosphorylation sites has motivated. Thus, a variety of computational methods
      have been developed for performing a large-scale prediction of kinase-specific
      phosphorylation sites. However, most of the proposed methods solely rely on the
      local amino acid sequences surrounding the phosphorylation sites. An increasing
      number of three-dimensional structures make it possible to physically investigate
      the structural environment of phosphorylation sites. RESULTS: In this work, all
      of the experimental phosphorylation sites are mapped to the protein entries of
      Protein Data Bank by sequence identity. It resulted in a total of 4508
      phosphorylation sites containing the protein three-dimensional (3D) structures.
      To identify phosphorylation sites on protein 3D structures, this work
      incorporates support vector machines (SVMs) with the information of linear motifs
      and spatial amino acid composition, which is determined for each kinase group by
      calculating the relative frequencies of 20 amino acid types within a specific
      radial distance from central phosphorylated amino acid residue. After the cross
      validation evaluation, most of the kinase-specific models trained with the
      consideration of structural information outperform the models considering only
      the sequence information. Furthermore, the independent testing set which is not
      included in training set has demonstrated that the proposed method could provide
      a comparable performance to other popular tools. CONCLUSION: The proposed method
      is shown to be capable of predicting kinase-specific phosphorylation sites on 3D
      structures and has been implemented as a web server which is freely accessible at
      http://csb.cse.yzu.edu.tw/PhosK3D/. Due to the difficulty of identifying the
      kinase-specific phosphorylation sites with similar sequenced motifs, this work
      also integrates the 3D structural information to improve the cross classifying
      specificity.

PMID- 24564523
TI  - FISH Amyloid - a new method for finding amyloidogenic segments in proteins based
      on site specific co-occurrence of aminoacids.
AB  - BACKGROUND: Amyloids are proteins capable of forming fibrils whose intramolecular
      contact sites assume densely packed zipper pattern. Their oligomers can underlie
      serious diseases, e.g. Alzheimer's and Parkinson's diseases. Recent studies show
      that short segments of aminoacids can be responsible for amyloidogenic properties
      of a protein. A few hundreds of such peptides have been experimentally found but
      experimental testing of all candidates is currently not feasible. Here we propose
      an original machine learning method for classification of aminoacid sequences,
      based on discovering a segment with a discriminative pattern of site-specific co
      occurrences between sequence elements. The pattern is based on the positions of
      residues with correlated occurrence over a sliding window of a specified length.
      The algorithm first recognizes the most relevant training segment in each
      positive training instance. Then the classification is based on maximal distances
      between co-occurrence matrix of the relevant segments in positive training
      sequences and the matrix from negative training segments. The method was applied
      for studying sequences of aminoacids with regard to their amyloidogenic
      properties. RESULTS: Our method was first trained on available datasets of
      hexapeptides with the amyloidogenic classification, using 5 or 6-residue sliding
      windows. Depending on the choice of training and testing datasets, the area under
      ROC curve obtained the value up to 0.80 for experimental, and 0.95 for
      computationally generated (with 3D profile method) datasets. Importantly, the
      results on 5-residue segments were not significantly worse, although the
      classification required that algorithm first recognized the most relevant
      training segments. The dataset of long sequences, such as sup35 prion and a few
      other amyloid proteins, were applied to test the method and gave encouraging
      results. Our web tool FISH Amyloid was trained on all available experimental data
      4-10 residues long, offers prediction of amyloidogenic segments in protein
      sequences. CONCLUSIONS: We proposed a new original classification method which
      recognizes co-occurrence patterns in sequences. The method reveals characteristic
      classification pattern of the data and finds the segments where its scoring is
      the strongest, also in long training sequences. Applied to the problem of
      amyloidogenic segments recognition, it showed a good potential for classification
      problems in bioinformatics.

PMID- 24564524
TI  - Lack of association between thrombophilic gene variants and recurrent pregnancy
      loss.
AB  - Recurrent pregnancy loss (RPL) is defined as the occurrence of two or more
      consecutive pregnancy losses. It is an important reproductive condition with a
      complex etiology. In approximately 50% of RPL cases an explanation for the cause
      is not found and they are therefore classified as idiopathic RPL. One of the
      causes implicated in RPL is thrombophilia, which consists of hemostatic disorders
      that lead to an increase in thromboembolic processes. The aim of this study was
      to evaluate polymorphic variants in genes related to thrombophilia as a risk
      factor in women with RPL. We investigated 145 women with at least two consecutive
      pregnancy losses and 135 women with at least two children and no history of
      pregnancy loss. Genotypes for the polymorphisms MTHFR C677T, FVL, FII
      (prothrombin), eNOS T-786C, and eNOS Glu298Asp were determined using a real-time
      PCR. Information about the exposure to environmental risk factors was also
      collected. There was no significant association between the environmental risk
      factors assessed and the polymorphisms studied. We did not find statistically
      significant differences in genotypic or allelic frequencies for the polymorphisms
      studied, in either the women with RPL or in the control group. Such polymorphisms
      should therefore not be considered as risk factors for this condition in this
      population.

PMID- 24564525
TI  - Design, synthesis, and structure-activity relationship studies of novel fused
      heterocycles-linked triazoles with good activity and water solubility.
AB  - Triazoles with fused-heterocycle nuclei were designed and evaluated for their in
      vitro activity on the basis of the binding mode of albaconazole using molecular
      docking, along with SAR of antifungal triazoles. Tetrahydro-[1,2,4]triazolo[1,5
      a]pyrazine and tetrahydro-thiazolo[5,4-c]pyridine nuclei were preferable to the
      other four fused-heterocycle nuclei investigated. Potent in vitro activity, broad
      spectrum and better water solubility were attained when triazoles containing
      nitrogen aromatic heterocycles were attached to these two nuclei. The most potent
      compounds 27aa and 45x, with low hERG inhibition and hepatocyte toxicity, both
      exhibited excellent activity against Candida, Cryptococcus, and Aspergillus spp.,
      as well as selected fluconazole-resistant strains. A high water-soluble compound
      58 (the disulfate salt of 45x) displayed unsatisfactory in vivo activity because
      of its poor PK profiles. Mice infected with C.alb. SC5314 and C.alb. 103
      (fluconazole-resistant strain) and administered with 27aa displayed significantly
      improved survival rates. 27aa also showed favorable pharmacokinetic (PK)
      profiles. 

PMID- 24564527
TI  - Impaired laryngopharyngeal sensitivity in patients with COPD: the association
      with swallow function.
AB  - Research indicates that patients with Chronic Obstructive Pulmonary Disease
      (COPD) have increased aspiration risk. Several factors may pre-dispose a patient
      to aspiration including a reduction in laryngopharyngeal sensitivity (LPS).
      Reduced LPS has been associated with increased aspiration risk in pathologies
      including stroke; however, this has not been examined in COPD. This study aims to
      explore possible associations between LPS and swallowing function in COPD
      patients, and determine whether a LPS predictive value may be used as a method of
      evaluating dysphagia risk in this patient population. Twenty participants with
      COPD underwent LPS discrimination testing, respiratory function testing, self
      reporting swallowing questionnaire, clinical swallowing examination, and fibre
      optic endoscopic evaluation of swallowing (FEES). Participants with COPD
      demonstrated impaired LPS defined by elevated laryngeal adductor reflex
      thresholds and high incidence of pharyngeal residue on FEES. Positive
      correlations were identified between their clinical swallowing examination and
      FEES results for the presence of laryngeal penetration/aspiration (p < 0.04),
      vallecular residue (p < 0.01), and piriform residue (p < 0.01). In conclusion,
      COPD patients have reduced laryngopharyngeal mechanosensitivity and impaired
      swallowing function characterized primarily by pharyngeal stasis. The combination
      of these deficits may place patients with COPD at increased aspiration risk due
      to lack of detection of pharyngeal residue and subsequent inhalation of
      pharyngeal contents.

PMID- 24564529
TI  - Absolute configuration determination using enantiomeric pairs of molecularly
      imprinted polymers.
AB  - A new method for determination of absolute configuration (AC) is demonstrated
      using an enantiomeric pair of molecularly imprinted polymers, referred to as
      "DuoMIPs". The ratio of HPLC capacity factors (k') for the analyte on each of the
      DuoMIPs is defined as the gamma factor and can be used to determine AC when above
      1.2. A mnemonic based on the complementary binding geometry of the DuoMIPs was
      used to aid in understanding and prediction of AC. 

PMID- 24564526
TI  - Transcriptional regulation prediction of antiestrogen resistance in breast cancer
      based on RNA polymerase II binding data.
AB  - BACKGROUND: Although endocrine therapy impedes estrogen-ER signaling pathway and
      thus reduces breast cancer mortality, patients remain at continued risk of
      relapse after tamoxifen or other endocrine therapies. Understanding the
      mechanisms of endocrine resistance, particularly the role of transcriptional
      regulation is very important and necessary. METHODS: We propose a two-step
      workflow based on linear model to investigate the significant differences between
      MCF7 and OHT cells stimulated by 17beta-estradiol (E2) respect to regulatory
      transcription factors (TFs) and their interactions. We additionally compared
      predicted regulatory TFs based on RNA polymerase II (PolII) binding quantity data
      and gene expression data, which were taken from MCF7/MCF7+E2 and OHT/OHT+E2 cell
      lines following the same analysis workflow. Enrichment analysis concerning
      diseases and cell functions and regulatory pattern analysis of different motifs
      of the same TF also were performed. RESULTS: The results showed PolII data could
      provide more information and predict more recognizably important regulatory TFs.
      Large differences in TF regulatory mode were found between two cell lines.
      Through verified through GO annotation, enrichment analysis and related
      literature regarding these TFs, we found some regulatory TFs such as AP-1, C/EBP,
      FoxA1, GATA1, Oct-1 and NF-kappaB, maintained OHT cells through molecular
      interactions or signaling pathways that were different from the surviving MCF7
      cells. From TF regulatory interaction network, we identified E2F, E2F-1 and AP-2
      as hub-TFs in MCF7 cells; whereas, in addition to E2F and E2F-1, we identified
      C/EBP and Oct-1 as hub-TFs in OHT cells. Notably, we found the regulatory
      patterns of different motifs of the same TF were very different from one another
      sometimes. CONCLUSIONS: We inferred some regulatory TFs, such as AP-1 and NF
      kappaB, cooperated with ER through both genomic action and non-genomic action.
      The TFs that were involved in both protein-protein interactions and signaling
      pathways could be one of the key resistant mechanisms of endocrine therapy and
      thus also could be new treatment targets for endocrine resistance. Our flexible
      workflow could be integrated into an existing analytical framework and guide
      biologists to further determine underlying mechanisms in human diseases.

PMID- 24564528
TI  - Cell-type and transcription factor specific enrichment of transcriptional
      cofactor motifs in ENCODE ChIP-seq data.
AB  - BACKGROUND: Cell type and TF specific interactions between Transcription Factors
      (TFs) and cofactors are essential for transcriptional regulation through
      recruitment of general transcription machinery to gene promoter regions and their
      identification heavily reliant on protein interaction assays. RESULTS: Using TF
      targeted chromatin immunoprecipitation coupled with massively parallel sequencing
      (ChIP-seq) data from Encyclopedia of DNA Elements (ENCODE), we report cell type
      and TF specific TF-cofactor interactions captured in vivo through enrichments of
      non target cofactor binding site motifs within ChIP-seq peaks. We observe
      enrichments in both known and novel cofactor motifs. CONCLUSIONS: Given the
      regulatory implications which TF and cofactor interactions have on a cell's
      phenotype, their identification is necessary but challenging. Here we present the
      findings to our analyses surrounding the investigation of TF-cofactor
      interactions encoded within TF ChIP-seq peaks. Novel cofactor binding site
      enrichments observed provides valuable insight into TF and cell type specific
      interactions driving TF interactions.

PMID- 24564531
TI  - Wetting transition on patterned surfaces: transition states and energy barriers.
AB  - We study the wetting transition on microstructured hydrophobic surfaces. We use
      the string method [J. Chem. Phys. 2007, 126, 164103; J. Chem. Phys. 2013, 138,
      134105] to accurately compute the transition states, the energy barriers, and the
      minimum energy paths for the wetting transition from the Cassie-Baxter state to
      the Wenzel state. Numerical results are obtained for the wetting of a hydrophobic
      surface textured with a square lattice of pillars. It is found that the wetting
      of the solid substrate occurs via infiltration of the liquid in a single groove,
      followed by lateral propagation of the liquid front. The propagation of the
      liquid front proceeds in a stepwise manner, and a zipping mechanism is observed
      during the infiltration of each layer. The minimum energy path for the wetting
      transition goes through a sequence of intermediate metastable states, whose
      wetted areas reflect the microstructure of the patterned surface. We also study
      the dependence of the energy barrier on the drop size and the gap between the
      pillars. 

PMID- 24564530
TI  - Regulation of the expression of the beta-lactam antibiotic-resistance
      determinants in methicillin-resistant Staphylococcus aureus (MRSA).
AB  - beta-Lactam antibiotics have faced obsolescence with the emergence of methicillin
      resistant Staphylococcus aureus (MRSA). A complex set of events ensues upon
      exposure of MRSA to these antibiotics, which culminates in proteolysis of BlaI or
      MecI, two gene repressors, and results in the induction of resistance. We report
      studies on the mechanism of binding of these gene repressors to the operator
      regions by fluorescence anisotropy. Within the range of in vivo concentrations
      for BlaI and MecI, these proteins interact with their regulatory elements in a
      reversible manner, as both a monomer and a dimer.

PMID- 24564532
TI  - Compared to controls, patients with ruptured aneurysm and surgical intervention
      show increase in symptoms of depression and lower cognitive performance, but
      their objective sleep is not affected.
AB  - OBJECTIVES: Patients with aneurysmal subarachnoid haemorrhage (aSAH) have
      impaired sleep and cognitive performance together with more difficulties in
      social and everyday life. Hypocortisolism has also been reported. However, a
      study assessing all dimensions between aSAH severity, objective and subjective
      sleep, cortisol secretion, cognitive performance and social and everyday life has
      not so far been performed. The aim of the present study was therefore two-fold:
      (1) to assess, in a sample of patients with aSAH, objective and subjective sleep,
      cognitive functioning, social skills and cortisol secretion concurrently, and (2)
      to compare patients on these variables with a control group. METHODS: Twenty-one
      patients (17 females; mean age: 58.80 years) with ruptured aneurysm and surgical
      intervention and 21 (14 females; mean age: 58.90 years) age- and gender-matched
      controls took part in the study. Assessments covered objective sleep-EGG
      recordings, subjective sleep, salivary cortisol analysis, and psychological
      functioning including memory performance, mood, and emotion recognition. RESULTS:
      Compared to healthy controls, patients had lower scores for verbal memory
      performance and emotion recognition; they also reported more marked depressive
      symptoms and complained of poor sleep. However, no differences were found for
      objective sleep or cortisol secretion. Subjective and objective sleep, cortisol
      secretion and psychological functioning were unrelated. CONCLUSIONS: Findings
      indicate that patients with aSAH face psychological rather than physiological
      issues.

PMID- 24564533
TI  - Investigation of melanocortin system gene variants in antipsychotic-induced
      weight gain.
AB  - OBJECTIVES: The use of second-generation antipsychotic medications may result in
      substantial weight gain in a subset of schizophrenia patients. Distinct
      populations of neurons expressed in the hypothalamus, including the cocaine- and
      amphetamine-regulated transcript (CART), the polypeptide pro-opiomelanocortin
      (POMC) and the agouti-related protein (AGRP), have regulatory roles in weight
      control and energy homeostasis. Thus, we investigated the potential role of CART,
      POMC and AGRP genetic variants in antipsychotic-induced weight gain (AIWG).
      METHODS: Five CART single nucleotide polymorphisms (SNPs) (rs10515115, rs3763153,
      rs3857384, rs11575893, rs16871471), three POMC SNPs (rs6713532, rs1047521,
      rs3754860) and one AGRP SNP (rs1338993), were genotyped in 218 patients treated
      with antipsychotics for chronic schizophrenia and evaluated for AIWG. We compared
      weight change (%) across genotypic groups using analysis of covariance. RESULTS:
      None of the SNPs in POMC, CART, AGRP were significantly associated with AIWG in
      the refined samples stratified by ethnicity and medication treatment.
      CONCLUSIONS: In this exploratory study, we observed that POMC, CART and AGRP gene
      variants are not a major contributor to AIWG. However larger samples are required
      to completely rule out their effect on AIWG.

PMID- 24564534
TI  - Impact of education and provision of complementary feeding on growth and
      morbidity in children less than 2 years of age in developing countries: a
      systematic review.
AB  - BACKGROUND: About one third of deaths in children less than 5 years of age are
      due to underlying undernutrition. According to an estimate, 19.4% of children <5
      years of age in developing countries were underweight (weight-for-age Z score <
      2) and about 29.9% were stunted in the year 2011 (height-for-age Z score <-2). It
      is well recognized that the period of 6-24 months of age is one of the most
      critical time for the growth of the infant. METHODS: We included randomized, non
      randomized trials and programs on the effect of complementary feeding (CF)
      (fortified or unfortified, but not micronutrients alone) and education on CF on
      children less than 2 years of age in low and middle income countries (LMIC).
      Studies that delivered intervention for at least 6 months were included; however,
      studies in which intervention was given for supplementary and therapeutic
      purposes were excluded. Recommendations are made for input to the Lives Saved
      Tool (LiST) model by following standardized guidelines developed by Child Health
      Epidemiology Reference Group (CHERG). RESULTS: We included 16 studies in this
      review. Amongst these, 9 studies provided education on complementary feeding, 6
      provided complementary feeding (with our without education) and 1 provided both
      as separate arms. Overall, education on CF alone significantly improved HAZ (SMD:
      0.23; 95% CI: 0.09, 0.36), WAZ (SMD 0.16, 95% CI: 0.05, 0.27), and significantly
      reduced the rates of stunting (RR 0.71; 95% CI: 0.56, 0.91). While no significant
      impact were observed for height and weight gain. Based on the subgroup analysis;
      ten studies from food secure populations indicated education on CF had a
      significant impact on height gain, HAZ scores, and weight gain, however, stunting
      reduced non-significantly. In food insecure population, CF education alone
      significantly improved HAZ scores, WAZ scores and significantly reduced the rates
      of stunting, while CF provision with or without education improved HAZ and WAZ
      scores significantly. CONCLUSION: Complementary feeding interventions have a
      potential to improve the nutritional status of children in developing countries.
      However, large scale high quality randomized controlled trials are required to
      assess the actual impact of this intervention on growth and morbidity in children
      6-24 months of age. Education should be combined with provision of complementary
      foods that are affordable, particularly for children in food insecure countries.

PMID- 24564536
TI  - In Vitro Antibiotic Susceptibility of Pseudomonas aeruginosa Corneal Ulcer
      Isolates.

PMID- 24564535
TI  - Tbx1 modulates endodermal and mesodermal differentiation from mouse induced
      pluripotent stem cells.
AB  - The T-box transcriptional factor (Tbx) family of transcriptional factors has
      distinct roles in a wide range of embryonic differentiation or response pathways.
      Tbx1, a T-box transcription factor, is an important gene for the human congenital
      disorder 22q11.2 deletion syndrome. Induced pluripotent stem cell (iPSC)
      technology offers new opportunities for both elucidation of the pathogenesis of
      diseases and the development of stem-cell-based therapies. In this study, we
      generated iPSCs from Tbx1(-/-) and Tbx1(+/+) fibroblasts and investigated the
      spontaneous differentiation potential of iPSCs by detailed lineage analysis of
      the iPSC-derived embryoid bodies. Undifferentiated Tbx1(-/-) and Tbx1(+/+) iPSCs
      showed similar expression levels of pluripotent markers. The ability of the Tbx1(
      /-) iPSCs to generate endodermal and mesodermal lineages was compromised upon
      spontaneous differentiation into embryonic bodies. Restoration of Tbx1 expression
      in the Tbx1(-/-) iPSCs to normal levels using an inducible lentiviral system
      rescued these cells from the potential of defective differentiation.
      Interestingly, overexpression of Tbx1 in the Tbx1(-/-) iPSCs to higher levels
      than in the Tbx1(+/+) iPSCs again led to a defective differentiation potential.
      Additionally, we observed that expression of fibroblast growth factor (FGF) 10
      and FGF8 was downregulated in the Tbx1(-/-) iPSC-derived cells, which suggests
      that Tbx1 regulates the expression of FGFs. Taken together, our results
      implicated the Tbx1 level as an important determinant of endodermal and
      mesodermal lineage differentiation during embryonic development. 

PMID- 24564537
TI  - Haploid to diploid alignment for variation calling assessment.
AB  - MOTIVATION: Variation calling is the process of detecting differences between
      donor and consensus DNA via high-throughput sequencing read mapping. When
      evaluating the performance of different variation calling methods, a typical
      scenario is to simulate artificial (diploid) genomes and sample reads from those.
      After variation calling, one can then compute precision and recall statistics.
      This works reliably on SNPs but on larger indels there is the problem of
      invariance: a predicted deletion/insertion can differ slightly from the true one,
      yet both make the same change to the genome. Also exactly correct predictions are
      rare, especially on larger insertions, so one should consider some notion of
      approximate predictions for fair comparison. RESULTS: We propose a full genome
      alignment-based strategy that allows for fair comparison of variation calling
      predictions: First, we apply the predicted variations to the consensus genome to
      create as many haploid genomes as are necessary to explain the variations.
      Second, we align the haploid genomes to the (aligned) artificial diploid genomes
      allowing arbitrary recombinations. The resulting haploid to diploid alignments
      tells how much the predictions differ from the true ones, solving the invariance
      issues in direct variation comparison. In an effort to make the approach scalable
      to real genomes, we develop a simple variant of the classical edit distance
      dynamic programming algorithm and apply the diagonal doubling technique to
      optimise the computation. We experiment with the approach on simulated
      predictions and also on real prediction data from a variation calling challenge.

PMID- 24564539
TI  - No generalization of practice for nonzero simple addition.
AB  - Several types of converging evidence have suggested recently that skilled adults
      solve very simple addition problems (e.g., 2 + 1, 4 + 2) using a fast,
      unconscious counting algorithm. These results stand in opposition to the long
      held assumption in the cognitive arithmetic literature that such simple addition
      problems normally are solved by fact retrieval from declarative memory. Here we
      tested a large sample of diversely skilled and culturally diverse men and women
      at the University of Saskatchewan and examined multiple categories of simple (1
      digit plus 1 digit) addition problems for evidence of generalization of practice,
      a signature of procedure use. The procedure-based 0 + N = N problems presented
      clear evidence of generalization (i.e., practicing a subset of 0 + N problems
      lead to speed-up for a different subset of 0 + N problems), but there was no
      evidence of such generalization of practice for the nonzero problems, although
      the experiment had good power to detect small effects. Given that generalization
      of practice is a basic marker of procedure-based processing, its absence for the
      nonzero addition problems casts doubt on the compacted counting theory.

PMID- 24564538
TI  - Impact of bilayer lipid composition on the structure and topology of the
      transmembrane amyloid precursor C99 protein.
AB  - C99 (also known as beta-CTF) is the 99 residue transmembrane C-terminal domain
      (residues 672-770) of the amyloid precursor protein and is the immediate
      precursor of the amyloid-beta (Abeta) polypeptides. To test the dependence of the
      C99 structure on the composition of the host model membranes, NMR studies of C99
      were conducted both in anionic lyso-myristoylphosphatidylglycerol (LMPG) micelles
      and in a series of five zwitterionic bicelle compositions involving
      phosphatidylcholine and sphingomyelin in which the acyl chain lengths of these
      lipid components varied from 14 to 24 carbons. Some of these mixtures are
      reported for the first time in this work and should be of broad utility in
      membrane protein research. The site-specific backbone (15)N and (1)H chemical
      shifts for C99 in LMPG and in all five bicelle mixtures were seen to be
      remarkably similar, indicating little dependence of the backbone structure of C99
      on the composition of the host model membrane. However, the length of the
      transmembrane span was seen to vary in a manner that alters the positioning of
      the gamma-secretase cleavage sites with respect to the center of the bilayer.
      This observation may contribute to the known dependency of the Abeta42-to-Abeta40
      production ratio on both membrane thickness and the length of the C99
      transmembrane domain. 

PMID- 24564541
TI  - Evidence for two attentional components in visual working memory.
AB  - How does executive attentional control contribute to memory for sequences of
      visual objects, and what does this reveal about storage and processing in working
      memory? Three experiments examined the impact of a concurrent executive load
      (backward counting) on memory for sequences of individually presented visual
      objects. Experiments 1 and 2 found disruptive concurrent load effects of
      equivalent magnitude on memory for shapes, colors, and colored shape conjunctions
      (as measured by single-probe recognition). These effects were present only for
      Items 1 and 2 in a 3-item sequence; the final item was always impervious to this
      disruption. This pattern of findings was precisely replicated in Experiment 3
      when using a cued verbal recall measure of shape-color binding, with error
      analysis providing additional insights concerning attention-related loss of early
      sequence items. These findings indicate an important role for executive processes
      in maintaining representations of earlier encountered stimuli in an active form
      alongside privileged storage of the most recent stimulus.

PMID- 24564540
TI  - Examining the relationship between immediate serial recall and immediate free
      recall: common effects of phonological loop variables but only limited evidence
      for the phonological loop.
AB  - We examined the contribution of the phonological loop to immediate free recall
      (IFR) and immediate serial recall (ISR) of lists of between one and 15 words.
      Following Baddeley (1986, 2000, 2007, 2012), we assumed that visual words could
      be recoded into the phonological store when presented silently but that recoding
      would be prevented by concurrent articulation (CA; Experiment 1). We further
      assumed that the use of the phonological loop would be evidenced by greater
      serial recall for lists of phonologically dissimilar words relative to lists of
      phonologically similar words (Experiments 2A and 2B). We found that in both
      tasks, (a) CA reduced recall; (b) participants recalled short lists from the
      start of the list, leading to enhanced forward-ordered recall; (c) participants
      were increasingly likely to recall longer lists from the end of the list, leading
      to extended recency effects; (d) there were significant phonological similarity
      effects in ISR and IFR when both were analyzed using serial recall scoring; (e)
      these were reduced by free recall scoring and eliminated by CA; and (f) CA but
      not phonological similarity affected the tendency to initiate recall with the
      first list item. We conclude that similar mechanisms underpin ISR and IFR.
      Critically, the phonological loop is not strictly necessary for the forward
      ordered recall of short lists on both tasks but may augment recall by increasing
      the accessibility of the list items (relative to CA), and in so doing, the order
      of later items is preserved better in phonologically dissimilar than in
      phonologically similar lists.

PMID- 24564542
TI  - The impact of storage on processing: how is information maintained in working
      memory?
AB  - Working memory is typically defined as a system devoted to the simultaneous
      maintenance and processing of information. However, the interplay between these 2
      functions is still a matter of debate in the literature, with views ranging from
      complete independence to complete dependence. The time-based resource-sharing
      model assumes that a central bottleneck constrains the 2 functions to alternate
      in such a way that maintenance activities postpone concurrent processing, with
      each additional piece of information to be maintained resulting in an additional
      postponement. Using different kinds of memoranda, we examined in a series of 7
      experiments the effect of increasing memory load on different processing tasks.
      The results reveal that, insofar as attention is needed for maintenance,
      processing times linearly increase at a rate of about 50 ms per verbal or
      visuospatial memory item, suggesting a very fast refresh rate in working memory.
      Our results also show an asymmetry between verbal and spatial information, in
      that spatial information can solely rely on attention for its maintenance while
      verbal information can also rely on a domain-specific maintenance mechanism
      independent from attention. The implications for the functioning of working
      memory are discussed, with a specific focus on how information is maintained in
      working memory.

PMID- 24564543
TI  - Is performance in task-cuing experiments mediated by task set selection or
      associative compound retrieval?
AB  - Task-cuing experiments are usually intended to explore control of task set. But
      when small stimulus sets are used, they plausibly afford learning of the response
      associated with a combination of cue and stimulus, without reference to tasks. In
      3 experiments we presented the typical trials of a task-cuing experiment: a cue
      (colored shape) followed, after a short or long interval, by a digit to which 1
      of 2 responses was required. In a tasks condition, participants were (as usual)
      directed to interpret the cue as an instruction to perform either an odd/even or
      a high/low classification task. In a cue + stimulus -> response (CSR) condition,
      to induce learning of mappings between cue-stimulus compound and response,
      participants were, in Experiment 1, given standard task instructions and
      additionally encouraged to learn the CSR mappings; in Experiment 2, informed of
      all the CSR mappings and asked to learn them, without standard task instructions;
      in Experiment 3, required to learn the mappings by trial and error. The effects
      of a task switch, response congruence, preparation, and transfer to a new set of
      stimuli differed substantially between the conditions in ways indicative of
      classification according to task rules in the tasks condition, and retrieval of
      responses specific to stimulus-cue combinations in the CSR conditions.
      Qualitative features of the latter could be captured by an associative learning
      network. Hence associatively based compound retrieval can serve as the basis for
      performance with a small stimulus set. But when organization by tasks is
      apparent, control via task set selection is the natural and efficient strategy.

PMID- 24564544
TI  - Relatedness proportion effects in semantic categorization: reconsidering the
      automatic spreading activation process.
AB  - Semantic priming effects at a short prime-target stimulus onset asynchrony are
      commonly explained in terms of an automatic spreading activation process.
      According to this view, the proportion of related trials should have no impact on
      the size of the semantic priming effect. Using a semantic categorization task
      ("Is this a living thing?"), we show that on the contrary, there is a robust
      effect of relatedness proportion on the size of the semantic priming effect. This
      effect is not due to the participants using the prime to predict the target
      category/response, as manipulating the proportion of category/response-congruent
      trials produces a very different pattern. Taken together with response time
      distribution analysis, we argue that the semantic priming effect observed here is
      best explained in terms of an evidence accumulation process and source confusion
      between the prime and target.

PMID- 24564545
TI  - A retrieved context account of spacing and repetition effects in free recall.
AB  - Repeating an item in a list benefits recall performance, and this benefit
      increases when the repetitions are spaced apart (Madigan, 1969; Melton, 1970).
      Retrieved context theory incorporates 2 mechanisms that account for these
      effects: contextual variability and study-phase retrieval. Specifically, if an
      item presented at position i is repeated at position j, this leads to retrieval
      of its context from its initial presentation at i (study-phase retrieval), and
      this retrieved context will be used to update the current state of context
      (contextual variability). Here we consider predictions of a computational model
      that embodies retrieved context theory, the context maintenance and retrieval
      model (CMR; Polyn, Norman, & Kahana, 2009). CMR makes the novel prediction that
      subjects are more likely to successively recall items that follow a shared
      repeated item (e.g., i + 1, j + 1) because both items are associated with the
      context of the repeated item presented at i and j. CMR also predicts that the
      probability of recalling at least 1 of 2 studied items should increase with the
      items' spacing (Lohnas, Polyn, & Kahana, 2011). We tested these predictions in a
      new experiment, and CMR's predictions were upheld. These findings suggest that
      retrieved context theory offers an integrated explanation for repetition and
      spacing effects in free recall tasks.

PMID- 24564546
TI  - Clinical features and gene mutational spectrum of CDKL5-related diseases in a
      cohort of Chinese patients.
AB  - BACKGROUND: Mutations in the cyclin-dependent kinase-like 5 (CDKL5) (NM_003159.2)
      gene have been associated with early-onset epileptic encephalopathies or Hanefeld
      variants of RTT(Rett syndrome). In order to clarify the CDKL5 genotype-phenotype
      correlations in Chinese patients, CDKL5 mutational screening in cases with early
      onset epileptic encephalopathies and RTT without MECP2 mutation were performed.
      METHODS: The detailed clinical information including clinical manifestation,
      electroencephalogram (EEG), magnetic resonance imaging (MRI), blood, urine amino
      acid and organic acid screening of 102 Chinese patients with early-onset
      epileptic encephalopathies and RTT were collected. CDKL5 gene mutations were
      analyzed by PCR, direct sequencing and multiplex ligation-dependent probe
      amplification (MLPA). The patterns of X-chromosome inactivation (XCI) were
      studied in the female patients with CDKL5 gene mutation. RESULTS: De novo CDKL5
      gene mutations were found in ten patients including one missense mutation (c.533G
      > A, p.R178Q) which had been reported, two splicing mutations (ISV6 + 1A > G,
      ISV13 + 1A > G), three micro-deletions (c.1111delC, c.2360delA, c.234delA), two
      insertions (c.1791 ins G, c.891_892 ins TT in a pair of twins) and one nonsense
      mutation (c.1375C > T, p.Q459X). Out of ten patients, 7 of 9 females with
      Hanefeld variants of RTT and the remaining 2 females with early onset epileptic
      encephalopathy, were detected while only one male with infantile spasms was
      detected. The common features of all female patients with CDKL5 gene mutations
      included refractory seizures starting before 4 months of age, severe psychomotor
      retardation, Rett-like features such as hand stereotypies, deceleration of head
      growth after birth and poor prognosis. In contrast, the only one male patient
      with CDKL5 mutation showed no obvious Rett-like features as females in our
      cohort. The X-chromosome inactivation patterns of all the female patients were
      random. CONCLUSIONS: Mutations in CDKL5 gene are responsible for 7 with Hanefeld
      variants of RTT and 2 with early-onset epileptic encephalopathy in 71 girls as
      well as for 1 infantile spasms in 31 males. There are some differences in the
      phenotypes among genders with CDKL5 gene mutations and CDKL5 gene mutation
      analysis should be considered in both genders.

PMID- 24564547
TI  - Cluster based prediction of PDZ-peptide interactions.
AB  - BACKGROUND: PDZ domains are one of the most promiscuous protein recognition
      modules that bind with short linear peptides and play an important role in
      cellular signaling. Recently, few high-throughput techniques (e.g. protein
      microarray screen, phage display) have been applied to determine in-vitro binding
      specificity of PDZ domains. Currently, many computational methods are available
      to predict PDZ-peptide interactions but they often provide domain specific models
      and/or have a limited domain coverage. RESULTS: Here, we composed the largest set
      of PDZ domains derived from human, mouse, fly and worm proteomes and defined
      binding models for PDZ domain families to improve the domain coverage and
      prediction specificity. For that purpose, we first identified a novel set of 138
      PDZ families, comprising of 548 PDZ domains from aforementioned organisms, based
      on efficient clustering according to their sequence identity. For 43 PDZ
      families, covering 226 PDZ domains with available interaction data, we built
      specialized models using a support vector machine approach. The advantage of
      family-wise models is that they can also be used to determine the binding
      specificity of a newly characterized PDZ domain with sufficient sequence identity
      to the known families. Since most current experimental approaches provide only
      positive data, we have to cope with the class imbalance problem. Thus, to enrich
      the negative class, we introduced a powerful semi-supervised technique to
      generate high confidence non-interaction data. We report competitive predictive
      performance with respect to state-of-the-art approaches. CONCLUSIONS: Our
      approach has several contributions. First, we show that domain coverage can be
      increased by applying accurate clustering technique. Second, we developed an
      approach based on a semi-supervised strategy to get high confidence negative
      data. Third, we allowed high order correlations between the amino acid positions
      in the binding peptides. Fourth, our method is general enough and will easily be
      applicable to other peptide recognition modules such as SH2 domains and finally,
      we performed a genome-wide prediction for 101 human and 102 mouse PDZ domains and
      uncovered novel interactions with biological relevance. We make all the
      predictive models and genome-wide predictions freely available to the scientific
      community.

PMID- 24564549
TI  - Factors governing change in water withdrawals for U.S. industrial sectors from
      1997 to 2002.
AB  - The United States Geological Survey (USGS) reports that U.S. water withdrawals
      have been steady since 1980, but the population and economy have grown since
      then. This implies that other factors have contributed to offsetting decreases in
      water withdrawals. Using water withdrawal data from USGS and economic data from
      Bureau of Economic Analysis (BEA), direct and total water withdrawals were
      estimated for 134 industrial summary sectors in the 1997 U.S. economic input
      output (EIO) table and 136 industrial sectors in the 2002 EIO table. Using
      structural decomposition analysis (SDA), the change in water withdrawals for the
      economy from 1997 to 2002 was allocated to changes in population, GDP per capita,
      water use intensity, production structure, and consumption patterns. The changes
      in population, GDP per capita, and water use intensity led to increased water
      withdrawals, while the changes in production structure and consumption patterns
      decreased water withdrawals from 1997 to 2002. Consumption patterns change was
      the largest net contributor to the change in water withdrawals. The model was
      used to predict aggregate changes in total water withdrawals from 2002 to 2010
      due to known changes in population and GDP per capita; a more complete model
      assessment must await release of updated data on USGS water withdrawals and EIO
      data. 

PMID- 24564548
TI  - Identification of gene fusions from human lung cancer mass spectrometry data.
AB  - BACKGROUND: Tandem mass spectrometry (MS/MS) technology has been applied to
      identify proteins, as an ultimate approach to confirm the original genome
      annotation. To be able to identify gene fusion proteins, a special database
      containing peptides that cross over gene fusion breakpoints is needed. METHODS:
      It is impractical to construct a database that includes all possible fusion
      peptides originated from potential breakpoints. Focusing on 6259 reported and
      predicted gene fusion pairs from ChimerDB 2.0 and Cancer Gene Census, we for the
      first time created a database CanProFu that comprehensively annotates fusion
      peptides formed by exon-exon linkage between these pairing genes. RESULTS:
      Applying this database to mass spectrometry datasets of 40 human non-small cell
      lung cancer (NSCLC) samples and 39 normal lung samples with stringent searching
      criteria, we were able to identify 19 unique fusion peptides characterizing gene
      fusion events. Among them 11 gene fusion events were only found in NSCLC samples.
      And also, 4 alternative splicing events were characterized in cancerous or normal
      lung samples. CONCLUSIONS: The database and workflow in this work can be flexibly
      applied to other MS/MS based human cancer experiments to detect gene fusions as
      potential disease biomarkers or drug targets.

PMID- 24564551
TI  - Phenotyping date palm varieties via leaflet cross-sectional imaging and
      artificial neural network application.
AB  - BACKGROUND: True date palms (Phoenix dactylifera L.) are impressive trees and
      have served as an indispensable source of food for mankind in tropical and
      subtropical countries for centuries. The aim of this study is to differentiate
      date palm tree varieties by analysing leaflet cross sections with
      technical/optical methods and artificial neural networks (ANN). RESULTS:
      Fluorescence microscopy images of leaflet cross sections have been taken from a
      set of five date palm tree cultivars (Hewlat al Jouf, Khlas, Nabot Soltan,
      Shishi, Um Raheem). After features extraction from images, the obtained data have
      been fed in a multilayer perceptron ANN with backpropagation learning algorithm.
      CONCLUSIONS: Overall, an accurate result in prediction and differentiation of
      date palm tree cultivars was achieved with average prediction in tenfold cross
      validation is 89.1% and reached 100% in one of the best ANN.

PMID- 24564550
TI  - Emollient therapy for preterm newborn infants--evidence from the developing
      world.
AB  - INTRODUCTION: Application of emollients is a widespread traditional newborn care
      practice in many low and middle-income countries (LMICs) and may have the
      potential to decrease infection and consequent mortality in preterm neonates.
      METHODS: We systematically reviewed literature published up to December 2012 to
      identify studies describing the effectiveness of emollient therapy. We used a
      standardized abstraction and grading format to estimate the effect of emollient
      therapy by applying the standard Child Health Epidemiology Reference Group
      (CHERG) rules. RESULTS: We included seven studies and one unpublished trial in
      this review. Topical emollient therapy significantly reduced neonatal mortality
      by 27% (RR: 0.73, 95% CI: 0.56, 0.94) and hospital acquired infection by 50% (RR:
      0.50, 95% CI: 0.36, 0.71). There were significant increases in weight (g) (MD:
      98.04, 95% CI: 42.64, 153.45) and weight gain (g/kg/day) (MD: 1.57, 95% CI: 0.79,
      2.36), whereas the impacts were non-significant for length and head
      circumference. CONCLUSION: Emollient therapy is associated with improved weight
      gain, reduced risk of infection and associated newborn mortality in preterm
      neonates and is a potentially promising intervention for use in low resource
      settings. Large scale effectiveness trials are required to further assess the
      impact of this intervention.

PMID- 24564552
TI  - Systematically profiling and annotating long intergenic non-coding RNAs in human
      embryonic stem cell.
AB  - BACKGROUND: While more and more long intergenic non-coding RNAs (lincRNAs) were
      identified to take important roles in both maintaining pluripotency and
      regulating differentiation, how these lincRNAs may define and drive cell fate
      decisions on a global scale are still mostly elusive. Systematical profiling and
      comprehensive annotation of embryonic stem cells lincRNAs may not only bring a
      clearer big picture of these novel regulators but also shed light on their
      functionalities. RESULTS: Based on multiple RNA-Seq datasets, we systematically
      identified 300 human embryonic stem cell lincRNAs (hES lincRNAs). Of which, one
      forth (78 out of 300) hES lincRNAs were further identified to be biasedly
      expressed in human ES cells. Functional analysis showed that they were
      preferentially involved in several early-development related biological
      processes. Comparative genomics analysis further suggested that around half of
      the identified hES lincRNAs were conserved in mouse. To facilitate further
      investigation of these hES lincRNAs, we constructed an online portal for
      biologists to access all their sequences and annotations interactively. In
      addition to navigation through a genome browse interface, users can also locate
      lincRNAs through an advanced query interface based on both keywords and
      expression profiles, and analyze results through multiple tools. CONCLUSIONS: By
      integrating multiple RNA-Seq datasets, we systematically characterized and
      annotated 300 hES lincRNAs. A full functional web portal is available freely at
      http://scbrowse.cbi.pku.edu.cn. As the first global profiling and annotating of
      human embryonic stem cell lincRNAs, this work aims to provide a valuable resource
      for both experimental biologists and bioinformaticians.

PMID- 24564553
TI  - Pathway-based drug repositioning using causal inference.
AB  - BACKGROUND: Recent in vivo studies showed new hopes of drug repositioning through
      causality inference from drugs to disease. Inspired by their success, here we
      present an in silico method for building a causal network (CauseNet) between
      drugs and diseases, in an attempt to systematically identify new therapeutic uses
      of existing drugs. METHODS: Unlike the traditional 'one drug-one target-one
      disease' causal model, we simultaneously consider all possible causal chains
      connecting drugs to diseases via target- and gene-involved pathways based on rich
      information in several expert-curated knowledge-bases. With statistical learning,
      our method estimates transition likelihood of each causal chain in the network
      based on known drug-disease treatment associations (e.g. bexarotene treats skin
      cancer). RESULTS: To demonstrate its validity, our method showed high performance
      (AUC = 0.859) in cross validation. Moreover, our top scored prediction results
      are highly enriched in literature and clinical trials. As a showcase of its
      utility, we show several drugs for potential re-use in Crohn's Disease.
      CONCLUSIONS: We successfully developed a computational method for discovering new
      uses of existing drugs based on casual inference in a layered drug-target-pathway
      gene- disease network. The results showed that our proposed method enables
      hypothesis generation from public accessible biological data for drug
      repositioning.

PMID- 24564556
TI  - Tumors of the anterior skull base.
AB  - A variety of histologic tumor types are present in the anterior skull base.
      Primary tumors of this area may be derived from the bone, paranasal sinuses,
      nasopharynx, dura, cranial nerves, pituitary gland and brain. Symptoms are caused
      mostly through mass effect but, if the tumor becomes aggressive, also through
      invasion. Selection of surgical approaches to the anterior skull base is based
      upon balancing risk reduction with maximizing extent of resection. Here we review
      a spectrum of neoplastic entities found in the anterior skull base in adults and
      discuss clinical and radiographic presentation, treatment options, and outcomes.
      Surgical resection remains the mainstay in treatment of these tumors,
      particularly in the hands of experienced surgeons exercising proper patient and
      case selection. 

PMID- 24564555
TI  - On the selection of appropriate distances for gene expression data clustering.
AB  - BACKGROUND: Clustering is crucial for gene expression data analysis. As an
      unsupervised exploratory procedure its results can help researchers to gain
      insights and formulate new hypothesis about biological data from microarrays.
      Given different settings of microarray experiments, clustering proves itself as a
      versatile exploratory tool. It can help to unveil new cancer subtypes or to
      identify groups of genes that respond similarly to a specific experimental
      condition. In order to obtain useful clustering results, however, different
      parameters of the clustering procedure must be properly tuned. Besides the
      selection of the clustering method itself, determining which distance is going to
      be employed between data objects is probably one of the most difficult decisions.
      RESULTS AND CONCLUSIONS: We analyze how different distances and clustering
      methods interact regarding their ability to cluster gene expression, i.e.,
      microarray data. We study 15 distances along with four common clustering methods
      from the literature on a total of 52 gene expression microarray datasets.
      Distances are evaluated on a number of different scenarios including clustering
      of cancer tissues and genes from short time-series expression data, the two main
      clustering applications in gene expression. Our results support that the
      selection of an appropriate distance depends on the scenario in hand. Moreover,
      in each scenario, given the very same clustering method, significant differences
      in quality may arise from the selection of distinct distance measures. In fact,
      the selection of an appropriate distance measure can make the difference between
      meaningful and poor clustering outcomes, even for a suitable clustering method.

PMID- 24564557
TI  - Intergenerational patterns of substance abuse among urban American Indian
      families.
AB  - Substance abuse continues to be a family problem in American Indian (AI)
      families. This article highlights findings from a two generation study on
      substance abuse among nine AI families. Five common themes shared by the parent
      and adult child groups included early onset of substance abuse, minimization of
      substance abuse (and a subtheme of efforts to control use), taking accountability
      for substance abuse (and a subtheme about perpetuated stereotypes), turning point
      moments in use (and a subtheme of negotiating and exploring sobriety), and
      perceptions of the abstinence only approach. Clinical implications are discussed
      in light of the findings. 

PMID- 24564558
TI  - Racial/ethnic variations in the influence of parental attachment on adolescent
      substance abuse.
AB  - This article examines whether the influence of parental attachment on adolescent
      substance abuse differs by race/ethnicity. We hypothesized that the effect of
      parental attachment would be stronger for Asian Americans than for other
      adolescents. Using data from the 2005 Fairfax County Communities That Care survey
      (N = 7,589), we found no support for our hypothesis. Results suggest that the
      effect of parental attachment on self-reported substance abuse differs
      dramatically by the race/ethnicity of the adolescent. Possible explanations for
      these findings are discussed.

PMID- 24564559
TI  - Drug offers as a context for violence perpetration and victimization.
AB  - Drug use has been linked empirically with and aggression and violence among youth
      in national and State of Hawai'i samples. However, the nature of this link and
      its implications for prevention are unclear. Therefore, this article explores the
      intersection of drugs with aggression and violence by using the drug offer
      context as the unit of analysis. Native Hawaiian youth are sampled because
      substance use rates tend to be higher and onset tends to be earlier for them than
      for their non-Hawaiian peers. Fourteen sex-specific focus group discussions were
      held with rural Native Hawaiian middle school students (N = 64). Students
      discussed what they think they would do in terms of drug refusal strategies in a
      variety of drug offer contexts. Although aggression and violence were perceived
      to be socially inappropriate, students nonetheless felt drug use would be less
      socially competent. Narrative analyses indicated that aggression and violence
      were thought to function as potential drug refusal strategies. As proximal drug
      resistance, aggression and violence perpetration served as an immediate deterrent
      to the drug offerer and thus drug use. As distal drug resistance, victimization
      served as a rationale for avoiding drug using contexts. Implications are
      discussed in terms of prevention policy and practice, specifically in terms of a
      school-based prevention curriculum. Future research in Hawaiian epistemology and
      gendered approaches are warranted. 

PMID- 24564560
TI  - Associations between race, ethnicity, religion, and waterpipe tobacco smoking.
AB  - We surveyed a random sample of 852 students at a large university in 2010-2011 to
      clarify associations between waterpipe tobacco smoking (WTS), ethnicity, and
      religion. Current (past 30 day) WTS was reported by 116 (14%) students, and 331
      (39%) reported ever WTS. Middle Eastern ethnicity was associated with current WTS
      (odds ratio [OR] = 2.37; 95% confidence interval [CI] = 1.06, 5.34) and ever WTS
      (OR = 2.59; 95% CI = 1.22, 5.47). South Asian ethnicity was associated with lower
      odds for ever WTS (OR = 0.42; 95% CI = 0.21, 0.86), but there was no significant
      association between South Asian ethnicity and current WTS. Being an atheist and
      having lower religiosity were associated with both WTS outcomes.

PMID- 24564562
TI  - The wisdom of pain.

PMID- 24564561
TI  - Dimensions of religion, depression symptomatology, and substance use among rural
      African American cocaine users.
AB  - Research has shown a relationship between depression, substance use, and
      religiosity but, few have investigated this relationship in a community sample of
      African Americans who use drugs. This study examined the relationship between
      dimensions of religion (positive and negative religious coping; private and
      public religious participation; religious preference; and God-, clergy-, and
      congregation-based religious support), depression symptomatology, and substance
      use among 223 African American cocaine users. After controlling for gender,
      employment, and age, greater congregation-based support and greater clergy-based
      support were associated with fewer reported depressive symptoms. In addition,
      greater congregation-based support was associated with less alcohol use. 

PMID- 24564563
TI  - Changing the breastfeeding conversation and our culture.

PMID- 24564564
TI  - Concordant integrative gene set enrichment analysis of multiple large-scale two
      sample expression data sets.
AB  - BACKGROUND: Gene set enrichment analysis (GSEA) is an important approach to the
      analysis of coordinate expression changes at a pathway level. Although many
      statistical and computational methods have been proposed for GSEA, the issue of a
      concordant integrative GSEA of multiple expression data sets has not been well
      addressed. Among different related data sets collected for the same or similar
      study purposes, it is important to identify pathways or gene sets with concordant
      enrichment. METHODS: We categorize the underlying true states of differential
      expression into three representative categories: no change, positive change and
      negative change. Due to data noise, what we observe from experiments may not
      indicate the underlying truth. Although these categories are not observed in
      practice, they can be considered in a mixture model framework. Then, we define
      the mathematical concept of concordant gene set enrichment and calculate its
      related probability based on a three-component multivariate normal mixture model.
      The related false discovery rate can be calculated and used to rank different
      gene sets. RESULTS: We used three published lung cancer microarray gene
      expression data sets to illustrate our proposed method. One analysis based on the
      first two data sets was conducted to compare our result with a previous published
      result based on a GSEA conducted separately for each individual data set. This
      comparison illustrates the advantage of our proposed concordant integrative gene
      set enrichment analysis. Then, with a relatively new and larger pathway
      collection, we used our method to conduct an integrative analysis of the first
      two data sets and also all three data sets. Both results showed that many gene
      sets could be identified with low false discovery rates. A consistency between
      both results was also observed. A further exploration based on the KEGG cancer
      pathway collection showed that a majority of these pathways could be identified
      by our proposed method. CONCLUSIONS: This study illustrates that we can improve
      detection power and discovery consistency through a concordant integrative
      analysis of multiple large-scale two-sample gene expression data sets.

PMID- 24564566
TI  - (-)-(2S,3R,Z)-Nakinadine A: first asymmetric synthesis and absolute configuration
      assignment.
AB  - Mannich-type reaction of methyl phenylacetate with the N-tert-butylsulfinyl imine
      derived from (R)-tert-butylsulfinamide and (Z)-14-(pyridin-3'-yl)tetradec-11-enal
      has been used as the key step in the first asymmetric synthesis of (-)-nakinadine
      A. Both the 2,3-syn- and 2,3-anti-diastereoisomers were prepared; comparison of
      spectroscopic and specific rotation data facilitated assignment of the absolute
      (2S,3R,Z)-configuration within the natural product. (-)-(2S,3R,Z)-Nakinadine A
      was prepared in 10 steps from 11-bromoundecan-1-ol, in 10% overall yield, 97:3 dr
      [(Z):(E) ratio], and >98% ee. 

PMID- 24564567
TI  - Combined phacoemulsification, primary intraocular lens implantation, and pars
      plana vitrectomy in children with uveitis.
AB  - PURPOSE: To evaluate the outcome of combined cataract surgery with primary
      intraocular lens (IOL) implantation and pars plana vitrectomy (PPV) in children
      with uveitis. METHODS: Data regarding visual acuity (VA), inflammatory status,
      medical therapy, and complications was collected from the medical charts of 17
      children (21 eyes) with chronic uveitis who underwent combined cataract surgery
      and PPV at the Eye Clinic, Sahlgrenska/Molndal, between 2002 and 2011. RESULTS:
      Seventy-six percent of the children had juvenile idiopathic arthritis. Median
      preoperative VA was 1.70 logMAR and median VA after 12 months was 0.17 logMAR.
      Postoperatively, glaucoma developed in 7 eyes, cystoid macular edema in 3 eyes,
      and visual axis opacification requiring treatment in 5 eyes. CONCLUSIONS:
      Although combined phacoemulsification, primary IOL implantation, and PPV in
      children with uveitis resulted in favorable visual outcome and stable
      inflammation in a majority of children, the technique should so far be reserved
      for uveitic cases with vitreous pathology.

PMID- 24564565
TI  - An evaluation of the emerging vaccines against influenza in children.
AB  - BACKGROUND: Influenza is an under-appreciated cause of acute lower respiratory
      infections (ALRI) in children. It is estimated to cause approximately 20 million
      new episodes of ALRI in children annually, 97% of these occurring in developing
      countries. It is also estimated to result in 28000 to 112000 deaths annually in
      young children. Apart from hospitalisations and deaths, influenza has significant
      economic consequences. The current egg-based inactivated influenza vaccines have
      several limitations: annual vaccination, high production costs, and cannot
      respond adequately to meet the demand during pandemics. METHODS: We used a
      modified CHNRI methodology for setting priorities in health research investments.
      This was done in two stages. In Stage I, we systematically reviewed the
      literature related to emerging cross-protective vaccines against influenza
      relevant to several criteria of interest: answerability; cost of development,
      production and implementation; efficacy and effectiveness; deliverability,
      affordability and sustainability; maximum potential impact on disease burden
      reduction; acceptability to the end users and health workers; and effect on
      equity. In Stage II, we conducted an expert opinion exercise by inviting 20
      experts (leading basic scientists, international public health researchers,
      international policy makers and representatives of pharmaceutical companies).
      They answered questions from the CHNRI framework and their "collective optimism"
      towards each criterion was documented on a scale from 0 to 100%. RESULTS: The
      experts expressed very high level of optimism for deliverability, impact on
      equity, and acceptability to health workers and end users. However, they
      expressed concerns over the criteria of answerability, low development cost, low
      product cost, low implementation cost, affordability and, to a lesser extent
      sustainability. In addition they felt that the vaccine would have higher efficacy
      and impact on disease burden reduction on overall influenza-associated disease
      rather than specifically influenza-associated pneumonia. CONCLUSION: Although the
      landscape of emerging influenza vaccines shows several promising candidates, it
      is unlikely that the advancements in the newer vaccine technologies will be able
      to progress through to large scale production in the near future. The combined
      effects of continued investments in researching new vaccines and improvements of
      available vaccines will hopefully shorten the time needed to the development of
      an effective seasonal and pandemic influenza vaccine suitable for large scale
      production.

PMID- 24564568
TI  - A retrospective analysis of hand tapping as a longitudinal marker of disease
      progression in Huntington's disease.
AB  - BACKGROUND: Current clinical assessments of motor function in Huntington's
      Disease (HD) rely on subjective ratings such as the Unified Huntington's Disease
      Rating scale (UHDRS). The ability to track disease progression using simple,
      objective, inexpensive, and robust measures would be beneficial. METHODS: One
      objective measure of motor performance is hand-tapping. Over the last 14 years we
      have routinely collected, using a simple device, the number of taps made by the
      right and left hand over 30 seconds in HD patients attending our NHS clinics.
      RESULTS: Here we report on a longitudinal cohort of 237 patients, which includes
      patients at all stages of the disease on a wide range of drug therapies. Hand
      tapping in these patients declines linearly at a rate of 5.1 taps per year (p <
      0.0001; 95% CI = 3.8 to 6.3 taps), and for each additional year of age patients
      could perform 0.9 fewer taps (main effect of age: p = 0.0007; 95% CI = 0.4 to
      1.4). Individual trajectories can vary widely around this average rate of
      decline, and much of this variation could be attributed to CAG repeat length.
      Genotype information was available for a subset of 151 patients, and for each
      additional repeat, patients could perform 5.6 fewer taps (p < 0.0001; 95% CI =
      3.3 to 8.0 taps), and progressed at a faster rate of 0.45 fewer taps per year
      (CAG by time interaction: p = 0.008; 95% CI = 0.12 to 0.78 taps). In addition,
      for each unit decrease in Total Functional Capacity (TFC) within individuals, the
      number of taps decreased by 6.3 (95% CI = 5.4 to 7.1, p < 0.0001). CONCLUSIONS:
      Hand tapping is a simple, robust, and reliable marker of disease progression. As
      such, this simple motor task could be a useful tool by which to assess disease
      progression as well therapies designed to slow it down.

PMID- 24564569
TI  - A simple, cost-effective but highly efficient system for deriving ventricular
      cardiomyocytes from human pluripotent stem cells.
AB  - Self-renewable human pluripotent stem cells (hPSCs) serve as a potential
      unlimited ex vivo source of human cardiomyocytes (CMs) for cell-based disease
      modeling and therapies. Although recent advances in directed differentiation
      protocols have enabled more efficient derivation of hPSC-derived CMs with an
      efficiency of ~50%-80% CMs and a final yield of ~1-20 CMs per starting
      undifferentiated hPSC, these protocols are often not readily transferrable across
      lines without first optimizing multiple parameters. Further, the resultant
      populations are undefined for chamber specificity or heterogeneous containing
      mixtures of atrial, ventricular (V), and pacemaker derivatives. Here we report a
      highly cost-effective and reproducibly efficient system for deriving hPSC
      ventricular cardiomyocytes (VCMs) from all five human embryonic stem cell (HES2,
      H7, and H9) and human induced PSC (hiPSC) (reprogrammed from human adult
      peripheral blood CD34(+) cells using nonintegrating episomal vectors) lines
      tested. Cardiogenic embryoid bodies could be formed by the sequential addition of
      BMP4, Rho kinase inhibitor, activin-A, and IWR-1. Spontaneously contracting
      clusters appeared as early as day 8. At day 16, up to 95% of cells were cTnT(+).
      Of which, 93%, 94%, 100%, 92%, and 92% of cardiac derivatives from HES2, H7, H9,
      and two iPSC lines, respectively, were VCMs as gauged by signature ventricular
      action potential and ionic currents (INa(+)/ICa,L(+)/IKr(+)/IKATP(+)); Ca(2+)
      transients showed positive chronotropic responses to beta-adrenergic stimulation.
      Our simple, cost-effective protocol required the least amounts of reagents and
      time compared with others. While the purity and percentage of PSC-VCMs were
      comparable to a recently published protocol, the present yield and efficiency
      with a final output of up to 70 hPSC-VCMs per hPSC was up to 5-fold higher and
      without the need of performing line-specific optimization. These differences were
      discussed. The results may lead to mass production of hPSC-VCMs in bioreactors.

PMID- 24564573
TI  - Is it time for preemptive drug treatment of asymptomatic (smoldering) multiple
      myeloma?
AB  - Asymptomatic (smoldering) multiple myeloma is a heterogeneous plasma cell
      proliferative disorder with a variable rate of progression to active multiple
      myeloma or related disorders. Hypercalcemia, renal insufficiency, anemia, bone
      lesions or recurrent bacterial infections characterize active multiple myeloma.
      Some patients with asymptomatic myeloma develop active disease rapidly, and
      others can stay asymptomatic for many years. Those who are likely to progress
      within the first 2 years of diagnosis have been categorized as having high-risk
      disease. The availability of novel agents in the treatment of active multiple
      myeloma and our better understanding of the heterogeneity of asymptomatic
      multiple myeloma have spurred interest in the early treatment of these patients.
      We have reviewed the current proposed definitions of high-risk asymptomatic
      multiple myeloma, the concerns about future therapy in view of the transient
      nature, remissions and toxicities of the therapies, and the eventual relapses
      that characterize this incurable disease.

PMID- 24564574
TI  - Biomimetic approach for liquid encapsulation with nanofibrillar cloaks.
AB  - Technologies that are able to handle microvolumes of liquids, such as
      microfluidics and liquid marbles, are attractive for applications that include
      miniaturized biological and chemical reactors, sensors, microactuators, and drug
      delivery systems. Inspired from natural fibrous envelopes, here, we present an
      innovative approach for liquid encapsulation and manipulation using electrospun
      nanofibers. We demonstrated the realization of non-wetting soft solids consisting
      of a liquid core wrapped in a hydrophobic fibrillar cloak of a fluoroacrylic
      copolymer and cellulose acetate. By properly controlling the wetting and
      mechanical properties of the fibers, we created final architectures with tunable
      mechanical robustness that were stable on a wide range of substrates (from paper
      to glass) and floated on liquid surfaces. Remarkably, the realized fiber-coated
      drops endured vortex mixing in a continuous oil phase at high stirring speed
      without bursting or water losses, favoring mixing processes inside the entrapped
      liquid volume. Moreover, the produced cloak can be easily functionalized by
      incorporating functional particles, active molecules, or drugs inside the
      nanofibers. 

PMID- 24564570
TI  - Diamidine compounds for selective inhibition of protein arginine
      methyltransferase 1.
AB  - Protein arginine methylation is a posttranslational modification critical for a
      variety of biological processes. Misregulation of protein arginine
      methyltransferases (PRMTs) has been linked to many pathological conditions. Most
      current PRMT inhibitors display limited specificity and selectivity,
      indiscriminately targeting many methyltransferase enzymes that use S-adenosyl-l
      methionine as a cofactor. Here we report diamidine compounds for specific
      inhibition of PRMT1, the primary type I enzyme. Docking, molecular dynamics, and
      MM/PBSA analysis together with biochemical assays were conducted to understand
      the binding modes of these inhibitors and the molecular basis of selective
      inhibition for PRMT1. Our data suggest that 2,5-bis(4-amidinophenyl)furan (1,
      furamidine, DB75), one leading inhibitor, targets the enzyme active site and is
      primarily competitive with the substrate and noncompetitive toward the cofactor.
      Furthermore, cellular studies revealed that 1 is cell membrane permeable and
      effectively inhibits intracellular PRMT1 activity and blocks cell proliferation
      in leukemia cell lines with different genetic lesions. 

PMID- 24564572
TI  - Clofarabine-associated acute kidney injury in patients undergoing hematopoietic
      stem cell transplant.
AB  - Abstract We examined clofarabine pharmacokinetics and association with renal
      toxicity in 62 patients participating in a phase I-II study of clofarabine
      melphalan-alemtuzumab conditioning for hematopoietic stem cell transplant (HSCT).
      Pharmacokinetic parameters, including clofarabine area under the concentration
      time curve (AUC), maximum concentration and clearance, were measured, and
      patients were monitored for renal injury. All patients had normal pretreatment
      creatinine values, but over half (55%) experienced acute kidney injury (AKI)
      after clofarabine administration. Age was the strongest predictor of AKI, with
      older patients at greater risk (p = 0.002). Clofarabine AUC was higher in
      patients who developed AKI, and patients with the highest dose-normalized AUCs
      experienced the most severe grades of AKI (p = 0.01). Lower baseline renal
      function, even when normal, was associated with lower clofarabine clearance (p =
      0.008). These data suggest that renal-adjustment of clofarabine dosing should be
      considered for older and at-risk patients even when renal function is ostensibly
      normal. 

PMID- 24564575
TI  - Synthesis and spectroscopy of PbSe fused quantum-dot dimers.
AB  - We report the synthesis and characterization of Pb-chalcogenide fused quantum-dot
      (QD) dimer structures. The resulting QD dimers range in length from 6 to 16 nm
      and are produced by oriented attachment of single QD monomers with diameters of
      3.1-7.8 nm. QD monomers with diameters exceeding about 5 nm appear to have the
      greatest affinity for QD dimer formation and, therefore, gave the greatest yields
      of fused structures. We find a new absorption feature in the first exciton QD
      dimer spectra and assign this to a splitting of the 8-fold degenerate 1S-level.
      The dimer splitting increases from 50 to 140 meV with decrease of the QD-monomer
      size, and we present a mechanism that accounts for this splitting. We also
      demonstrate the possibility of fusing two QDs with different sizes into a
      heterostructure. 

PMID- 24564576
TI  - Cellphone camera imaging of a periodically patterned chip as a potential method
      for point-of-care diagnostics.
AB  - In this study, we demonstrate that a disposable chip periodically patterned with
      suitable ligands, an ordinary cellphone camera, and a simple pattern recognition
      software, can potentially be used for quantitative diagnostics. A key factor in
      this demonstration is the design of a calibration grid around the chip that,
      through a contrast transfer process, enables reliable analysis of the images
      collected under variable ambient lighting conditions. After exposure to a
      dispersion of amine terminated silica beads used as analyte mimicking pathogens,
      an epoxy-terminated glass substrate microcontact printed with
      octadecyltrichlorosilane (250 MUm periodicity) developed a characteristic pattern
      of beads which could be easily imaged with a cellphone camera of 3.2 MP pixels. A
      simple pattern recognition algorithm using fast Fourier transform produced a
      quantitative estimate of the analyte concentration present in the test solution.
      In this method importantly, neither the chip fabrication process nor the fill
      factor of the periodic pattern need be perfect to arrive at a conclusive
      diagnosis. The method suggests a viable platform that may potentially find use in
      fault-tolerant and robust point-of-care diagnostic applications. 

PMID- 24564577
TI  - Changes in the distribution of high-risk births associated with changes in
      contraceptive prevalence.
AB  - BACKGROUND: Several birth characteristics are associated with high mortality
      risk: very young or old mothers, short birth intervals and high birth order. One
      justification for family planning programs is the health benefits associated with
      better spacing and timing of births. This study examines the extent to which the
      prevalence of these risk factors changes as a country transitions from high to
      low fertility. METHODS: We use data from 194 national surveys to examine both
      cross section and within-country variation in these risk factors as they relate
      to the total fertility rate. RESULTS: Declines in the total fertility rate are
      associated with large declines in the proportion of high order births, those to
      mothers over the age of 34 and those with multiple risk factors; as well as to
      increasing proportions of first order births. There is little change in the
      proportion of births with short birth intervals except in sub-Saharan Africa. The
      use of family planning is strongly associated with fertility declines.
      CONCLUSIONS: The proportion of second and higher order births with demographic
      risk factors declines substantially as fertility declines. This creates a
      potential for reducing child mortality rates. Some of the reduction comes from
      modifying the birth interval distribution or by bringing maternal age at the time
      of birth into the 'safe' range of 18-35 years, and some comes from the actual
      elimination of births that would have a high mortality risk (high parity births).

PMID- 24564578
TI  - Mining the tissue-tissue gene co-expression network for tumor microenvironment
      study and biomarker prediction.
AB  - BACKGROUND: Recent discovery in tumor development indicates that the tumor
      microenvironment (mostly stroma cells) plays an important role in cancer
      development. To understand how the tumor microenvironment (TME) interacts with
      the tumor, we explore the correlation of the gene expressions between tumor and
      stroma. The tumor and stroma gene expression data are modeled as a weighted
      bipartite network (tumor-stroma coexpression network) where the weight of an edge
      indicates the correlation between the expression profiles of the corresponding
      tumor gene and stroma gene. In order to efficiently mine this weighted bipartite
      network, we developed the Bipartite subnetwork Component Mining algorithm (BCM),
      and we show that the BCM algorithm can efficiently mine weighted bipartite
      networks for dense Bipartite sub-Networks (BiNets) with density guarantees.
      RESULTS: We applied BCM to the tumor-stroma coexpression network and find 372
      BiNets that demonstrate statistical significance in survival tests. A good number
      of these BiNets demonstrate strong prognosis powers on at least one breast cancer
      patient cohort, which suggests that these BiNets are potential biomarkers for
      breast cancer prognosis. Further study on these 372 BiNets by the network merging
      approach reveals that they form 10 macro bipartite networks which show
      orchestrated key biological processes in both tumor and stroma. In addition, by
      further examining the BiNets that are significant in ER-negative breast cancer
      patient prognosis, we discovered a ubiquitin C (UBC) gene network that
      demonstrates strong prognosis power in nearly all types of breast cancer subtypes
      we used in this study. CONCLUSIONS: The results support our hypothesis that the
      UBC gene network plays an important role in breast cancer prognosis and therapy
      and it is a potential prognostic biomarker for multiple breast cancer subtypes.

PMID- 24564579
TI  - The de novo sequence origin of two long non-coding genes from an inter-genic
      region.
AB  - BACKGROUND: The gene Polymorphic derived intron-containing, known as Pldi, is a
      long non-coding RNA (lncRNA) first discovered in mouse. Although parts of its
      sequence were reported to be conserved in rat and human, it can only be expressed
      in mouse testis with a mouse-specific transcription start site. The consensus
      sequence of Pldi is also part of an antisense transcript AK158810 expressed in a
      wide range of mouse tissues. RESULT: We focused on sequence origin of Pldi and
      Ak158810. We demonstrated that their sequence was originated from an inter-genic
      region and is only presented in mammalians. Transposable events and chromosome
      rearrangements were involved in the evolution of ancestral sequence. Moreover, we
      discovered high conservation in part of this region was correlated with
      chromosome rearrangements, CpG demethylation and transcriptional factor binding
      motif. These results demonstrated that multiple factors contributed to the
      sequence origin of Pldi. CONCLUSIONS: We comprehensively analyzed the sequence
      origin of Pldi-Ak158810 loci. We provided various factors, including
      rearrangement, transposable elements, contributed to the formation of the
      sequence.

PMID- 24564581
TI  - Simple whole-cell biodetection and bioremediation of heavy metals based on an
      engineered lead-specific operon.
AB  - A lead-specific binding protein, PbrR, and promoter pbr from the lead resistance
      operon, pbr, of Cupriavidus metallidurans CH34 was incorporated into E. coli in
      conjunction with an engineered downstream RFP (red fluorescence protein), which
      allowed for highly sensitive and selective whole-cell detection of lead ions. The
      subsequent display of PbrR on the E. coli cell surface permitted selective
      adsorption of lead ions from solution containing various heavy metal ions. The
      surface-engineered E. coli bacteria effectively protected Arabidopsis thaliana
      seed germination from the toxicity of lead ions at high concentrations.
      Engineering the E. coli bacteria harboring these lead-specific elements from the
      pbr operon may potentially be a valuable general strategy for biodetection and
      bioremediation of toxic heavy metal ions in the environment. 

PMID- 24564580
TI  - Using distances between Top-n-gram and residue pairs for protein remote homology
      detection.
AB  - BACKGROUND: Protein remote homology detection is one of the central problems in
      bioinformatics, which is important for both basic research and practical
      application. Currently, discriminative methods based on Support Vector Machines
      (SVMs) achieve the state-of-the-art performance. Exploring feature vectors
      incorporating the position information of amino acids or other protein building
      blocks is a key step to improve the performance of the SVM-based methods.
      RESULTS: Two new methods for protein remote homology detection were proposed,
      called SVM-DR and SVM-DT. SVM-DR is a sequence-based method, in which the feature
      vector representation for protein is based on the distances between residue
      pairs. SVM-DT is a profile-based method, which considers the distances between
      Top-n-gram pairs. Top-n-gram can be viewed as a profile-based building block of
      proteins, which is calculated from the frequency profiles. These two methods are
      position dependent approaches incorporating the sequence-order information of
      protein sequences. Various experiments were conducted on a benchmark dataset
      containing 54 families and 23 superfamilies. Experimental results showed that
      these two new methods are very promising. Compared with the position independent
      methods, the performance improvement is obvious. Furthermore, the proposed
      methods can also provide useful insights for studying the features of protein
      families. CONCLUSION: The better performance of the proposed methods demonstrates
      that the position dependant approaches are efficient for protein remote homology
      detection. Another advantage of our methods arises from the explicit feature
      space representation, which can be used to analyze the characteristic features of
      protein families. The source code of SVM-DT and SVM-DR is available at
      http://bioinformatics.hitsz.edu.cn/DistanceSVM/index.jsp.

PMID- 24564582
TI  - Anodic titania nanotubes grown on titanium tubular electrodes.
AB  - In the past decade, research into growth and application of anodic titania
      nanotubes has been focused on planar titanium electrodes. Although patterned,
      curved, or cylindrical substrates were also employed in a number of applications,
      the study of nanotubes grown on a titanium tubular electrode is rather
      inadequate, despite their expected uses in thermal fluids. In this study, growth
      of titania nanotubes on tubular electrodes was investigated. It was found that
      nanotubes are formed at both outer and inner surfaces of the electrode. The
      nanotube length (or growth rate in the first 30 min) at the outer surface
      decreases gradually from the side facing the cathode to that at the other side,
      while the length at the inner surface smears out this trend. This is due to the
      effect of the electric field emanating from the potential drop in the organic
      electrolyte. The variation of nanotube diameter just echoes such a tendency of
      potential drop. The influence of electrode orientation during anodization on the
      resulting features of nanotubes was also examined and discussed. The nanotube
      geometry is thus tailorable for particular applications. 

PMID- 24564583
TI  - iview: an interactive WebGL visualizer for protein-ligand complex.
AB  - BACKGROUND: Visualization of protein-ligand complex plays an important role in
      elaborating protein-ligand interactions and aiding novel drug design. Most
      existing web visualizers either rely on slow software rendering, or lack virtual
      reality support. The vital feature of macromolecular surface construction is also
      unavailable. RESULTS: We have developed iview, an easy-to-use interactive WebGL
      visualizer of protein-ligand complex. It exploits hardware acceleration rather
      than software rendering. It features three special effects in virtual reality
      settings, namely anaglyph, parallax barrier and oculus rift, resulting in
      visually appealing identification of intermolecular interactions. It supports
      four surface representations including Van der Waals surface, solvent excluded
      surface, solvent accessible surface and molecular surface. Moreover, based on the
      feature-rich version of iview, we have also developed a neat and tailor-made
      version specifically for our istar web platform for protein-ligand docking
      purpose. This demonstrates the excellent portability of iview. CONCLUSIONS: Using
      innovative 3D techniques, we provide a user friendly visualizer that is not
      intended to compete with professional visualizers, but to enable easy
      accessibility and platform independence.

PMID- 24564585
TI  - Life Cycle Assessment (ISO 14040) implementation in foods of animal and plant
      origin: review.
AB  - The importance of environmental protection has been recently upgraded due to the
      continuously increasing environmental pollution load. Life Cycle Assessment
      (LCA), wellknown as ISO 14040, has been repeatedly shown to be a useful and
      powerful tool for assessing the environmental performance of industrial
      processes, both in the European and American continents as well as in many Asian
      countries (such as Japan and China). To the best of our knowledge, almost no
      information is provided in relation to LCA implementation in Africa apart from an
      article related to Egypt. Although food industries are not considered to be among
      the most heavily polluting ones, for some like olive oil, wine, dairy, and meat
      processing, their impact on the environment is a heavy burden. The introduction
      of LCA aimed at identifying both inputs and outputs to find out which are the
      most detrimental to the environment in terms of water/energy consumption and
      solid/liquid and gas releases. In this review, a thorough coverage of literature
      was made in an attempt to compare the implementation of LCA to a variety of
      products of both plant and animal origin. It was concluded that there is a high
      number of subsystems suggested for the same product, thereby, occasionally
      leading to confusion. An idea toward solving the problem is to proceed to some
      sort of standardization by means of several generic case studies of LCA
      implementation, similarly to what had happened in the case of Hazard Analysis and
      Critical Control Points (HACCP) implementation in the United States, Canada,
      Australia, United Kingdom, and other countries.

PMID- 24564586
TI  - Pretreatments for the efficient extraction of bioactive compounds from plant
      based biomaterials.
AB  - The extraction of medicinal or functional compounds from herbal plants is an
      important unit operation in food and bio-industries. The target compounds are
      generally present inter- or intra-cellularly in an intricate microstructure
      formed by cells, intercellular spaces, capillaries, and pores. The major
      resistance of molecular diffusion in materials of plant origin always comes from
      the intact cell walls and adhering membranes. Therefore, increasing the
      permeability of cell walls and membranes plays a very important role to increase
      extraction yield and/or extraction rate. Important pretreatment methods to modify
      the cellular structures and increase the permeability of cell walls or membranes
      are discussed in this paper. They include physical, biologic, and chemical
      treatments. In physical methods, mechanical disruption, high-pressure (HP)
      process, pulsed electric field (PEF) application, ultrasonic treatment, and
      freeze-thaw, and so on were applied. In biologic methods, different cell wall
      degrading enzymes were applied to break-down cell walls or membranes and to
      diminish the overall internal resistance for transporting bioactive compounds
      from internal matrix to the external solution. In chemical methods, various
      chemicals for increasing the inner- or outer-membrane permeabilization were
      introduced. The principles of the technologies, examples of improvements, and
      advantages and disadvantages of the pretreatment methods are critically reviewed
      in this paper.

PMID- 24564587
TI  - Immunity: plants as effective mediators.
AB  - In the domain of nutrition, exploring the diet-health linkages is major area of
      research. The outcomes of such interventions led to widespread acceptance of
      functional and nutraceutical foods; however, augmenting immunity is a major
      concern of dietary regimens. Indeed, the immune system is incredible arrangement
      of specific organs and cells that enabled humans to carry out defense against
      undesired responses. Its proper functionality is essential to maintain the body
      homeostasis. Array of plants and their components hold immunomodulating
      properties. Their possible inclusion in diets could explore new therapeutic
      avenues to enhanced immunity against diseases. The review intended to highlight
      the importance of garlic (Allium sativum), green tea (Camellia sinensis), ginger
      (Zingiber officinale), purple coneflower (Echinacea), black cumin (Nigella
      sativa), licorice (Glycyrrhiza glabra), Astragalus and St. John's wort (Hypericum
      perforatum) as natural immune boosters. These plants are bestowed with functional
      ingredients that may provide protection against various menaces. Modes of their
      actions include boosting and functioning of immune system, activation and
      suppression of immune specialized cells, interfering in several pathways that
      eventually led to improvement in immune responses and defense system. In
      addition, some of these plants carry free radical scavenging and anti
      inflammatory activities that are helpful against cancer insurgence. Nevertheless,
      interaction between drugs and herbs/botanicals should be well investigated before
      recommended for their safe use, and such information must be disseminated to the
      allied stakeholders.

PMID- 24564588
TI  - Cheddar cheese ripening and flavor characterization: a review.
AB  - Cheddar cheese is a biochemically dynamic product that undergoes significant
      changes during ripening. Freshly made curds of various cheese varieties have
      bland and largely similar flavors and aroma and, during ripening, flavoring
      compounds are produced that are characteristic of each variety. The biochemical
      changes occurring during ripening are grouped into primary events including
      glycolysis, lipolysis, and proteolysis followed by secondary biochemical changes
      such as metabolism of fatty acids and amino acids which are important for the
      production of secondary metabolites, including a number of compounds necessary
      for flavor development. A key feature of cheese manufacture is the metabolism of
      lactose to lactate by selected cultures of lactic acid bacteria. The rate and
      extent of acidification influence the initial texture of the curd by controlling
      the rate of demineralization. The degree of lipolysis in cheese depends on the
      variety of cheese and may vary from slight to extensive; however, proteolysis is
      the most complex of the primary events during cheese ripening, especially in
      Cheddar-type cheese.

PMID- 24564589
TI  - The hypoglycemic effect of pumpkin seeds, Trigonelline (TRG), Nicotinic acid
      (NA), and D-Chiro-inositol (DCI) in controlling glycemic levels in diabetes
      mellitus.
AB  - In the contemporary society, diabetes mellitus is considered as a common,
      growing, serious, costly, and potentially preventable public health problem. It
      is forecasted that in 2030, the number of people with diabetes will go up from
      117 million in 2000 to 366 million in 2030. The prevalence of diabetes will place
      a huge burden on health and financial structures of countries, and these will
      impact on individuals, as well as families and nations. Polysaccharides, para
      aminobenzoic acid, fixed oils, sterol, proteins, and peptides are biologically
      active ingredients, which are found in pumpkins. The chemicals within pumpkins
      such as the fruit pulp, oil from ungerminated seeds, and protein from germinated
      seeds have hypoglycemic properties. Preliminary investigation showed that pumpkin
      seeds, and the macromolecules, therein, such as Trigonelline (TRG), Nicotinic
      acid (NA), and D-chiro-inositol (DCI), possess hypoglycemic properties and could
      assist in maintaining glycemic control.

PMID- 24564584
TI  - Human stem cells for craniomaxillofacial reconstruction.
AB  - Human stem cell research represents an exceptional opportunity for regenerative
      medicine and the surgical reconstruction of the craniomaxillofacial complex. The
      correct architecture and function of the vastly diverse tissues of this important
      anatomical region are critical for life supportive processes, the delivery of
      senses, social interaction, and aesthetics. Craniomaxillofacial tissue loss is
      commonly associated with inflammatory responses of the surrounding tissue,
      significant scarring, disfigurement, and psychological sequelae as an inevitable
      consequence. The in vitro production of fully functional cells for skin, muscle,
      cartilage, bone, and neurovascular tissue formation from human stem cells, may
      one day provide novel materials for the reconstructive surgeon operating on
      patients with both hard and soft tissue deficit due to cancer, congenital
      disease, or trauma. However, the clinical translation of human stem cell
      technology, including the application of human pluripotent stem cells (hPSCs) in
      novel regenerative therapies, faces several hurdles that must be solved to permit
      safe and effective use in patients. The basic biology of hPSCs remains to be
      fully elucidated and concerns of tumorigenicity need to be addressed, prior to
      the development of cell transplantation treatments. Furthermore, functional
      comparison of in vitro generated tissue to their in vivo counterparts will be
      necessary for confirmation of maturity and suitability for application in
      reconstructive surgery. Here, we provide an overview of human stem cells in
      disease modeling, drug screening, and therapeutics, while also discussing the
      application of regenerative medicine for craniomaxillofacial tissue deficit and
      surgical reconstruction. 

PMID- 24564590
TI  - Brain evolution, the determinates of food choice, and the omnivore's dilemma.
AB  - A coevolutionary paradigm using a biocultural perspective can help to unravel the
      complex interactions that led to the contemporary pattern of eating. Evolutionary
      history helps to understand the adaptation of diet and its nutritional
      implications. Anatomical and behavioral changes linked to changing dietary
      patterns in the Paleolithic resulted in an adaptive framework that affects modern
      diet. The evolution of an expanding brain, a shrinking large intestine, and
      lengthening small intestine necessitated a demand for nutritionally dense foods.
      The key to these changes is an understanding of the response to the omnivore's
      dilemma. Omnivores in their search for new items to feed their varied diet
      (neophilia) have a challenge when they fear (neophobia) novel items that may be
      poisonous and can cause death. The inborn mechanism initiates palate fatigue
      (sensory-specific satiety) ensuring a variety of foods will be eaten. Variety
      will limit the impact of toxins ingested and provide a more balanced diet. The
      development of cuisine, a momentous event in history, mediated the conflict, and
      changed the course of human evolution. The cuisine, a biocultural construct,
      defines which items found in nature are edible, how these products are
      transformed into food, the flavors used to add a sensory dimension to foods, and
      rules of eating or etiquette. Etiquette defines how, when, and with whom we eat.
      Patterns of eating in the modern setting are the end product of the way that Homo
      sapiens evolved and resolved the omnivore's dilemma. Control of fire and cooking
      expanded the range of available foods by creating a class of foods that are
      "predigested." An essential element to the evolution of the human diet was the
      transition to agriculture as the primary mode of subsistence. The Neolithic
      revolution dramatically narrowed the dietary niche by decreasing the variety of
      available foods, with the shift to intensive agriculture creating a dramatic
      decline in human nutrition. The recent industrialization of the world food system
      has resulted in a nutritional transition in which developing nations are
      simultaneously experiencing undernutrition and obesity. In addition, an abundance
      of inexpensive, high-density foods laden with sugar and fats is available to a
      population that expends little energy to obtain such large numbers of calories.
      Furthermore, the abundant variety of ultraprocessed foods overrides the sensory
      specific satiety mechanism leading to overconsumption.

PMID- 24564591
TI  - Structure, function, and nutrition of phytoferritin: a newly functional factor
      for iron supplement.
AB  - Ferritins are members of the superfamily of iron storage and detoxification
      proteins present in all living organisms and play important roles in controlling
      cellular iron homeostasis. In contrast to animal ferritin, relatively little
      information is available on the structure and function of phytoferritin.
      Phytoferritin is observed in plastids whereas animal ferritins are largely found
      in the cytoplasm of cell. Compared to animal ferritin, phytoferritin exhibits two
      major distinctive features in structure. First, phytoferritin contains a specific
      extension peptide (EP) at the N-terminal while animal ferritin lacks it. The EP
      is located on the exterior surface of protein, which recently has been found to
      act as a second ferroxidase center for iron-binding and oxidation, and regulate
      iron release during the germination and early growth of seedlings. Second, only H
      type subunit has been identified in phytoferritin, which is usually a
      heteropolymer consisting of two different subunits, H-1 and H-2, sharing ~80%
      amino acid sequence identity. These two subunits in phytoferritin play a
      positively cooperative role in iron oxidative deposition in protein. Iron
      deficiency anemia (IDA) is the most common and widespread nutritional disorder in
      the world, so it is crucial to explore a safe and efficient functional factor for
      iron supplement. Fortunately, phytoferritin seems to be a suitable candidate. In
      legume seeds, more than 90% of iron is stored in the form of ferritin in
      amyloplasts. Recently, some studies at different levels have demonstrated that
      plant ferritin could be used as novel, utilizable, plant-based forms of iron for
      populations with a low iron status. This review focuses on recent progress in
      structure, function, and nutrition of phytoferritin.

PMID- 24564592
TI  - Thermoplastic starch processing and characteristics-a review.
AB  - Canola Council of Canada, Winnipeg, Manitoba, Canada The rising costs of
      nonrenewable feedstocks and environmental concerns with their industrial usage
      have encouraged the study and development of renewable products, including
      thermoplastic starch (TPS). Starch is an abundant, plant-based biodegradable
      material with interesting physicochemical characteristics that can be exploited,
      and this has received attention for development of TPS products. Starch exhibits
      usable thermoplastic properties when plasticizers, elevated temperatures, and
      shear are present. The choice of plasticizer has an effect on TPS, even when
      these have similar plasticization principles. Most TPS have glass transition
      temperature, Tg, in the range of approximately -75 to 10 degrees C. Glassy
      transition of TPS is detected by differential scanning calorimeter (DSC) and
      thermodynamic analyzer (DMA), although DMA has been found to be more sensitive
      and effective. TPS has low tensile properties, typically below 6 MPa in tensile
      strength (TS). The addition of synthetic polymers, nanoclay, and fiber can
      improve TS and water-resistance ability. The moisture sorption behavior of TPS is
      described in GAB and BET models, from which monolayer moisture content and
      specific area are derived. Current studies on surface tension, gas permeability,
      crystallinity, and so on of the TPS are also reviewed.

PMID- 24564593
TI  - Thermal inactivation of microorganisms.
AB  - This paper serves as an overview of various aspects of thermal processing. Heat
      processing of foods has a long history and is still one of the most important
      preservation methods. To guarantee microbiological safety and stability, large
      safety margins are often applied in traditional heat processes. Because of the
      need for more fresh like foods, there is a need for milder preservation methods
      without compromising on safety and stability. The review deals with heat
      resistance data and mathematical models that describe heat inactivation. The
      effects of food composition are not yet fully clear and more knowledge of the
      cell physiology of the target microorganism could be of help in predicting the
      effects of food constituents. Finally, special attention has been paid to
      biological time temperature indicators to enable proper process calculations. 

PMID- 24564594
TI  - Instant noodles: processing, quality, and nutritional aspects.
AB  - Noodles are one of the staple foods consumed in many Asian countries. Instant
      noodles have become internationally recognized food, and worldwide consumption is
      on the rise. The properties of instant noodles like taste, nutrition,
      convenience, safety, longer shelf-life, and reasonable price have made them
      popular. Quality factors important for instant noodles are color, flavor, and
      texture, cooking quality, rehydration rates during final preparation, and the
      presence or absence of rancid taste after extended storage. Microstructure of
      dough and noodles has been studied to understand the influence of ingredients and
      processing variables on the noodle quality by employing scanning electron
      microscopy. Applications of newer techniques like confocal laser scanning
      microscopy and epifluorescence light microscopy employed to understand the
      microstructure changes in dough and noodles have also been discussed. Sincere
      efforts of researchers are underway to improve the formulation, extend the shelf
      life, and promote universal fortification of instant noodles. Accordingly, many
      researchers are exploring the potential of noodle fortification as an effective
      public health intervention and improve its nutritional properties. This review
      focuses on the functionality of ingredients, unit operations involved, quality
      criteria for evaluation, recent trends in fortification, and current knowledge in
      relation to instant noodles.

PMID- 24564595
TI  - Microscopic Polyangiitis Manifesting as Lymphoma.

PMID- 24564596
TI  - Proteasomes in lungs from organ donors and patients with end-stage pulmonary
      diseases.
AB  - Proteasomes appear to be involved in the pathophysiology of various acute and
      chronic lung diseases. Information on the human lung proteasome in health and
      disease, however, is sparse. Therefore, we studied whether end-stage pulmonary
      diseases are associated with alterations in lung 20S/26S proteasome content,
      activity and 20S subunit composition. Biopsies were obtained from donor lungs
      (n=7) and explanted lungs from patients undergoing lung transplantation because
      of end stage chronic obstructive pulmonary disease (COPD; n=7), idiopathic
      pulmonary fibrosis (IPF, n=7) and pulmonary sarcoidosis (n=5). 20S/26S
      proteasomes in lung extracts were quantified by ELISA, chymotrypsin-like
      proteasome peptidase activities measured and 20S proteasome beta subunits
      analyzed by Western blot. As compared with donor lungs, proteasome content was
      increased in IPF and sarcoidosis, but not in COPD. The relative distribution of
      free 20S and 26S proteasomes was similar; 20S proteasome was predominant in all
      extracts. Proteasome peptidase activities in donor and diseased lungs were
      indistinguishable. All extracts contained a mixed composition of inducible 20S
      beta immuno-subunits and their constitutive counterparts; a disease associated
      distribution could not be identified. A higher content of lung proteasomes in IPF
      and pulmonary sarcoidosis may contribute to the pathophysiology of human fibrotic
      lung diseases. 

PMID- 24564597
TI  - Disturbance of the magnetic field did not affect spatial memory.
AB  - Extremely low-frequency magnetic field (ELF-MF) has been suggested to influence
      the cognitive capability but this should be dynamically evaluated in a
      longitudinal study. Previous training can affect performance, but the influence
      under magnetic field is unclear. This study aims to evaluate the effects of
      previous training and ELF-MF exposure on learning and memory using the Morris
      water maze (MWM). Sprague-Dawley rats were subjected to MWM training, ELF-MF
      exposure (50 Hz, 100 microT), or ELF-MF exposure combined with MWM training for
      90 days. Normal rats were used as controls. The MWM was used to test. The data
      show that the rats exposed to training and ELF-MF with training performed better
      on spatial acquisition when re-tested. However, during the probe trial the rats
      showed no change between the training phase and the test phase. Compared with the
      control group, the ELF-MF group showed no significant differences. These results
      confirm that previous training can improve the learning and memory capabilities
      regarding spatial acquisition in the MWM and this effect can last for at least 90
      days. However, this improvement in learning and memory capabilities was not
      observed during the probe trial. Furthermore, ELF-MF exposure did not interfere
      with the improvement in learning and memory capabilities. 

PMID- 24564598
TI  - Determinants of adrenal androgen hypofunction in premenopausal females with
      rheumatoid arthritis.
AB  - The aim of our study was to investigate adrenocortical function in the context of
      disease activity and inflammatory status in premenopausal RA females. Adrenal
      glucocorticoid and androgen responses to the 1 microg ACTH 1-24 test were
      investigated in 23 premenopausal RA and in 15 age- and BMI-matched healthy
      females. Twelve RA patients were on low-dose prednisone (<8.5 mg/day). Patients
      with DAS28>3.2 had lower (p<0.05) total plasma cortisol, 17-hydroxyprogesterone,
      dehydroepiandrosterone and androstenedione responses in the ACTH test compared to
      healthy controls. Patients with DAS28>3.2 had lower (p<0.05)
      dehydroepiandrosterone response in the ACTH test compared to patients with
      DAS28</=3.2. C-reactive protein (CRP), DAS28, and interleukin (IL)-6 negatively
      correlated with androstenedione response to ACTH 1-24. Responses of all measured
      adrenal steroids were lower (p<0.05) in patients on low-dose glucocorticoids
      compared to healthy controls. RA patients not treated with glucocorticoids had
      lower total cortisol response (p=0.038) but did not differ in free plasma
      cortisol in the ACTH test. The results indicate an association of increased
      disease activity with a decrease in adrenal androgen production in RA and normal
      cortisol bioavailability in patients not treated with glucocorticoids. 

PMID- 24564599
TI  - Riboflavin supplementation improves energy metabolism in mice exposed to acute
      hypoxia.
AB  - This study investigated the effects of riboflavin on energy metabolism in hypoxic
      mice. Kunming mice were fed diets containing riboflavin at doses of 6, 12, 24 and
      48 mg/kg, respectively for 2 weeks before exposure to a simulated altitude of
      6000 m for 8 h. Changes of riboflavin status and energy metabolism were assessed
      biochemically. Simultaneously, a (1)H nuclear magnetic resonance (NMR) based
      metabolomic technique was used to track the changes of plasma metabolic
      profiling. It was found that the content of hepatic riboflavin was decreased and
      erythrocyte glutathione activation coefficient was elevated significantly under
      hypoxic condition. Meanwhile, increased plasma pyruvate, lactate, beta
      hydroxybutyrate and urea, as well as decreased plasma carnitine were observed.
      Riboflavin supplementation improved riboflavin status remarkably in hypoxic mice
      and decreased plasma levels of pyruvate, free fatty acids and beta
      hydroxybutyrate significantly. Plasma carnitine was increased in response to
      riboflavin supplementation. Results obtained from (1)H NMR analysis were
      basically in line with the data from biochemical assays and remarkable changes in
      plasma taurine, choline and some other metabolites were also indicated. It was
      concluded that riboflavin requirement was increased under acute hypoxic condition
      and riboflavin supplementation was effective in improving energy metabolism in
      hypoxic mice. 

PMID- 24564600
TI  - Effect of sex hormones on plasma phospholipid fatty acid composition in intact
      rats and rats with bilaterally occluded carotid arteries.
AB  - The effects of 8-days treatment with 17alpha-estradiol (33.3 microg/kg) and
      progesterone (1.7 mg/kg) on plasma lipids and fatty acid composition of plasma
      phospholipids were examined in intact (INT) and bilaterally common carotid
      arteries occluded (BCO) male Wistar rats. Significant decrease of triglyceride
      level was found in BCO rats after the estradiol treatment. Both hormones elevated
      proportion of 18:1n-7 fatty acid in INT, but they failed to have such an effect
      in BCO. Estradiol increased 22:5n-3 and total n-3 polyunsaturated fatty acids
      (PUFA) in intact, and decreased 18:2n-6 in BCO rats. Significantly lower level of
      total n-3 was found in progesterone-treated than in estradiol-treated BCO rats.
      Given that n-3 PUFA have many beneficial effects on cell and tissue function,
      while n-6 PUFA have mostly the opposite effects, estradiol, rather than
      progesterone, was seen to improve plasma lipids and phospholipids FA profiles in
      INT and BCO animals. Estradiol significantly elevated the estimated activity of
      delta9-desaturases and progesterone of delta5-desaturase in BCO group, with no
      effects in INT rats. 

PMID- 24564601
TI  - The effect of heme oxygenase on ganglioside redistribution within hepatocytes in
      experimental estrogen-induced cholestasis.
AB  - Cholestasis is characterized by the elevation of serum total bile acids (TBA),
      which leads to the production of both free radicals and oxidative stress.
      Although they do not share the same mechanisms, membrane glycosphingolipids (GSL)
      and the antioxidant enzyme heme oxygenase-1 (HMOX1) both act against the pro
      oxidative effect of TBA. The aim of the study was to assess the role of HMOX on
      GSL redistribution and composition within hepatocytes in the rat model of
      estrogen-induced cholestasis. Compared to the controls, an increase of total
      gangliosides in the liver homogenates of the cholestatic group (P=0.001) was
      detected; further, it paralleled along with the activation of their biosynthetic
      b-branch pathway (P<0.01). These effects were partially prevented by HMOX
      activation. Cholestasis was accompanied by a redistribution of GM1 ganglioside
      from the cytoplasm to the sinusoids; while HMOX activation led to the retention
      of GM1 in the cytoplasm (P=0.014). Our study shows that estrogen-induced
      cholestasis is followed by changes in the synthesis and/or distribution of GSL.
      These changes are not only triggered by the detergent power of accumulated TBA,
      but also by their pro-oxidant action. Increases in the antioxidant defenses might
      represent an important supportive therapeutic measure for patients with
      cholestatic liver disease. 

PMID- 24564602
TI  - Monitoring of glycation, oxidative stress and inflammation in relation to the
      occurrence of vascular complications in patients with type 2 diabetes mellitus.
AB  - The study aimed to evaluate if the monitoring of advanced glycation end products
      (AGEs), advanced oxidation protein products (AOPP), lipoperoxides (LPO) and
      interleukin-6 (IL-6) in plasma could help to predict development of diabetic
      complications (DC). Clinical and biochemical parameters including AGEs, AOPP, LPO
      and IL-6 were investigated in patients with type 2 diabetes mellitus (DM2) with
      (+DC) and without (-DC) complications. AGEs were significantly higher in both
      diabetic groups compared to controls. AGEs were also significantly higher in
      group +DC compared to -DC. AGEs significantly correlated with HbA1c. We observed
      significantly higher AOPP in both diabetic groups in comparison with controls,
      but the difference between -DC and +DC was not significant. LPO significantly
      correlated with BMI. IL-6 were significantly increased in both diabetic groups
      compared to controls, but the difference between -DC and +DC was not significant.
      There was no significant correlation between IL-6 and clinical and biochemical
      parameters. These results do not exclude the association between IL-6 and onset
      of DC. We suggest that the measurement of not only HbA1c, but also AGEs may be
      useful to predict the risk of DC development in clinical practice. Furthermore,
      the measurement of IL-6 should be studied as adjunct to HbA1c monitoring. 

PMID- 24564603
TI  - Low dose domoic acid influences spontaneous behavior in adult rats.
AB  - Domoic acid (DA) is a potent marine neurotoxine present in seafood. Intoxication
      by DA causes gastrointestinal symptoms like vomiting and diarrhoea and also the
      so-called amnesic shellfish poisoning (inflicting memory impairment and
      seizures). Since exposure to non-convulsive doses is relevant to the human
      health, we investigated the effect of low dose DA administration in adult Wistar
      rats. Rats were administered with DA at the dose 1.0 mg/kg and their behavior was
      monitored for one hour in three sessions. The first session started immediately
      after DA administration. The second and third session started one and two weeks
      later. After the third session, the histochemical analysis of the hippocampi of
      the animals was conducted (Fluoro-Jade B, bis-benzimide). DA increased time spent
      by locomotion and distance travelled in the second half of the first session and
      this effect was pronounced during the second and third session. Exploratory
      rearing was decreased by DA administration in the first half of the first
      session. DA influenced the grooming in biphasic manner (decrease followed by an
      increase of time spent by grooming). This biphasic trend was observed even two
      weeks after the DA administration. Histochemistry of DA treated rats did not
      confirm the presence of apoptotic bodies, Fluoro-Jade B positive cells were not
      found neither in CA1 nor CA3 area of the hippocampi. Our study revealed that a
      low dose of DA affect short and long-term the spontaneous behavior of rats
      without inducing neuronal damage. 

PMID- 24564604
TI  - Novel method for detection of reactive oxygen species in vivo in human skeletal
      muscle.
AB  - Excessive production of reactive oxygen species (ROS) are implicated in the
      pathogenesis of numerous disease states. However, direct measurement of in vivo
      ROS in humans has remained elusive due to limited access to appropriate tissue
      beds and the inherently short half-lives and high reactivity of ROS. Herein, we
      describe a novel technique by which to measure in vivo ROS in human skeletal
      muscle. Microdialysis probes were inserted into the vastus lateralis of eight
      healthy volunteers. Amplex Ultrared, a highly specific fluorogenic substrate for
      hydrogen peroxide (H(2)O(2)), and horseradish peroxidase (HRP), were perfused
      through microdialysis probes, and outflowing dialysate was collected and
      fluorescence was measured. Extracellular H(2)O(2) that crossed the microdialysis
      membrane was measured via fluorescence of the dialysate. Superoxide dismutase
      (SOD) was then added to the inflowing perfusion media to convert any superoxide
      crossing the microdialysis membrane to H(2)O(2) within the microdialysis probe.
      Fluorescence significantly increased (P=0.005) upon SOD addition. These data
      demonstrate the feasibility of measuring both in vivo H(2)O(2) and superoxide in
      the extracellular environment of human skeletal muscle, providing a technique
      with a potential application to a wide range of circulatory and metabolic studies
      of oxidative stress. 

PMID- 24564605
TI  - Anemia in adenine-induced chronic renal failure and the influence of treatment
      with gum acacia thereon.
AB  - Anemia frequently complicates chronic kidney disease (CKD). We investigated here
      the effect of adenine-induced CKD in rats on erythrocyte count (EC), hematocrit
      (PCV) and hemoglobin (Hb) concentration, as well as on the activity of L-gamma
      glutamyl transferase (GGT) and the concentrations of iron (Fe), transferrin (Tf),
      ferritin (F), total iron binding capacity (TIBC) / unsaturated iron binding
      capacity (UIBC) and hepcidin (Hp) in serum and erythropoietin (Epo) in renal
      tissue. Renal damage was assessed histopathologically, and also by measuring the
      serum concentrations of the uremic toxin indoxyl sulfate (IS), creatinine, and
      urea, and by creatinine clearance. We also assessed the influence of concomitant
      treatment with gum acacia (GA) on the above analytes. Adenine feeding induced
      CKD, accompanied by significant decreases (P<0.05) in EC, PCV, and Hb, and in the
      serum concentrations of Fe, Tf, TIBC, UIBC and Epo. It also increased Hp and F
      levels. GA significantly ameliorated these changes in rats with CKD. A general
      improvement in the renal status of rats with CKD after GA is shown due to its
      anti-inflammatory and anti-oxidant actions, and reduction of the uremic toxin IS,
      which is known to suppress Epo production, and this may be a reason for its
      ameliorative actions on the indices of anemia studied. 

PMID- 24564606
TI  - Pulse transit time and blood pressure during cardiopulmonary exercise tests.
AB  - Pulse transit time (PTT), the interval between ventricular electrical activity
      and peripheral pulse wave, is assumed to be a surrogate marker for blood pressure
      (BP) changes. The objective of this study was to analyze PTT and its relation to
      BP during cardiopulmonary exercise tests (CPET). In 20 patients (mean age 51+/
      18.4 years), ECG and finger-photoplethysmography were continuously recorded
      during routine CPETs. PTT was calculated for each R-wave in the ECG and the
      steepest slope of the corresponding upstroke in the plethysmogram. For each
      subject, linear and non-linear regression models were used to assess the relation
      between PTT and upper-arm oscillometric BP in 9 predefined measuring points
      including measurements at rest, during exercise and during recovery. Mean
      systolic BP (sBP) and PTT at rest were 128 mm Hg and 366 ms respectively, 197 mm
      Hg and 289 ms under maximum exercise, and 128 mm Hg and 371 ms during recovery.
      Linear regression showed a significant, strong negative correlation between PTT
      and sBP. The correlation between PTT and diastolic BP was rather weak. Bland
      Altman plots of sBP values estimated by the regression functions revealed
      slightly better limits of agreements for the non-linear model (-10.9 to 10.9 mm
      Hg) than for the linear model (-13.2 to 13.1 mm Hg). These results indicate that
      PTT is a good potential surrogate measure for sBP during exercise and could
      easily be implemented in CPET as an additional parameter of cardiovascular
      reactivity. A non-linear approach might be more effective in estimating BP than
      linear regression. 

PMID- 24564607
TI  - The economics of abiraterone acetate for castration-resistant prostate cancer.
AB  - Abiraterone acetate is an oral medication that has recently been granted approval
      for the treatment of metastatic castration resistant prostate cancer (mCRPC)
      prior and/or after chemotherapy with docetaxel. In this article we assess the
      economics of abiraterone acetate in mCRPC. Relevant studies demonstrated that
      abiraterone acetate had a minimal budget impact on health plans. A relevant
      advantage was the cost savings due to the lack of chemotherapy-related side
      effects as well as the ease of administration. The results of cost/benefit
      comparative studies with other novel agents (i.e. cabazitaxel, enzalutamide,
      sipuleucel-T) are warranted as well as the close collaboration between urologists
      and medical oncologists. 

PMID- 24564609
TI  - cellXpress: a fast and user-friendly software platform for profiling cellular
      phenotypes.
AB  - BACKGROUND: High-throughput, image-based screens of cellular responses to genetic
      or chemical perturbations generate huge numbers of cell images. Automated
      analysis is required to quantify and compare the effects of these perturbations.
      However, few of the current freely-available bioimage analysis software tools are
      optimized for efficient handling of these images. Even fewer of them are designed
      to transform the phenotypic features measured from these images into
      discriminative profiles that can reveal biologically meaningful associations
      among the tested perturbations. RESULTS: We present a fast and user-friendly
      software platform called "cellXpress" to segment cells, measure quantitative
      features of cellular phenotypes, construct discriminative profiles, and visualize
      the resulting cell masks and feature values. We have also developed a suite of
      library functions to load the extracted features for further customizable
      analysis and visualization under the R computing environment. We systematically
      compared the processing speed, cell segmentation accuracy, and phenotypic-profile
      clustering performance of cellXpress to other existing bioimage analysis software
      packages or algorithms. We found that cellXpress outperforms these existing tools
      on three different bioimage datasets. We estimate that cellXpress could finish
      processing a genome-wide gene knockdown image dataset in less than a day on a
      modern personal desktop computer. CONCLUSIONS: The cellXpress platform is
      designed to make fast and efficient high-throughput phenotypic profiling more
      accessible to the wider biological research community. The cellXpress
      installation packages for 64-bit Windows and Linux, user manual, installation
      guide, and datasets used in this analysis can be downloaded freely from
      http://www.cellXpress.org.

PMID- 24564608
TI  - Structural basis for the identification of the N-terminal domain of coronavirus
      nucleocapsid protein as an antiviral target.
AB  - Coronaviruses (CoVs) cause numerous diseases, including Middle East respiratory
      syndrome and severe acute respiratory syndrome, generating significant health
      related and economic consequences. CoVs encode the nucleocapsid (N) protein, a
      major structural protein that plays multiple roles in the virus replication cycle
      and forms a ribonucleoprotein complex with the viral RNA through the N protein's
      N-terminal domain (N-NTD). Using human CoV-OC43 (HCoV-OC43) as a model for CoV,
      we present the 3D structure of HCoV-OC43 N-NTD complexed with ribonucleoside 5'
      monophosphates to identify a distinct ribonucleotide-binding pocket. By targeting
      this pocket, we identified and developed a new coronavirus N protein inhibitor, N
      (6-oxo-5,6-dihydrophenanthridin-2-yl)(N,N-dimethylamino)acetamide hydrochloride
      (PJ34), using virtual screening; this inhibitor reduced the N protein's RNA
      binding affinity and hindered viral replication. We also determined the crystal
      structure of the N-NTD-PJ34 complex. On the basis of these findings, we propose
      guidelines for developing new N protein-based antiviral agents that target CoVs. 

PMID- 24564611
TI  - Low-shrink composite resins: a review of their history, strategies for managing
      shrinkage, and clinical significance.
AB  - Despite numerous advances in composite resin technology over the course of many
      decades, shrinkage behavior and the resultant stresses inherent to direct placed
      composite restorations continue to challenge clinicians. This overview of
      composite resins includes a review of their history and development along with a
      discussion of strategies for reducing polymerization shrinkage. An assessment of
      the clinical significance of these materials is also provided, including a
      discussion of the differences between polymerization shrinkage and stress,
      incremental layering versus bulk placement, and the emergence of lower shrinkage
      stress monomer chemistry. 

PMID- 24564610
TI  - Characterization and treatment of postsurgical dental implant pain employing
      intranasal ketorolac.
AB  - The intensity and duration of pain following surgical placement of dental
      implants has not been well studied. Thus, the aim of this open-label study was to
      characterize the nature of postsurgical pain following the placement of one to
      three implants. The secondary goal was to explore the analgesic efficacy and
      tolerability of intranasal ketorolac in this patient population. Following
      implant surgery, postoperative pain was rated moderate or severe in 25/28
      patients (89 percent), requiring prn analgesic dosing for up to 3 days in 14/25
      individuals (56 percent). Intranasal ketorolac displayed an analgesic onset
      within 20 minutes, a duration of at least 6 hours, and was well tolerated by the
      cohort with brief stinging of the nasal mucosa reported by 9/25 individuals (36
      percent). 

PMID- 24564612
TI  - Bonded functional esthetic prototype: an alternative pre-treatment mock-up
      technique and cost-effective medium-term esthetic solution.
AB  - As the economy has receded in recent years, many patients have been inclined to
      reject dental treatment beyond what they feel is the minimal amount necessary.
      Increasingly, there has been reluctance to take on the expense of full-mouth
      restorations and time-consuming procedures. Consequently, clinicians can benefit
      from innovative, conservative, interim solutions that enable them to provide
      segment treatment with long-term stability and esthetics, with lower initial
      cost. The bonded functional esthetic prototype (BFEP) allows fabrication of up to
      14 teeth from composite in 1 hour, providing either a pre-treatment restoration
      or a long-term provisional solution until further treatment can be completed. As
      demonstrated herein, the BFEP enables superb function, stability, and esthetics
      in the interim while dispersing the cost of definitive treatment over time. 

PMID- 24564613
TI  - Lingual orthodontics: accelerated realignment of the "social six" with
      piezocision.
AB  - Despite the growing number of adults interested in improving their smiles through
      orthodontic treatment, the visual impact and the duration of the treatment itself
      are frequently obstacles to patient acceptance. A treatment that is fast and less
      visible is a desirable option that adult patients often request of their
      orthodontists. Presented in this case report, which involves a young woman who
      wanted treatment completed in a limited amount of time, is a new application of a
      minimally invasive surgical approach to accelerate orthodontic movement combined
      with a simplified 2-dimensional lingual orthodontic treatment to resolve mild
      crowding in the anterior region, otherwise known as the "social six.". 

PMID- 24564614
TI  - CAD/CAM implant abutments using coded healing abutments: a detailed description
      of the restorative process.
AB  - Computer-aided design/computer-aided manufacturing (CAD/CAM) represents a leap
      forward in the fabrication of implant restorations. Coded healing abutments can
      be digitally read, and they eliminate the steps needed to make implant
      impressions using traditional impression copings. This article provides a
      detailed description of the restorative process using CAD/CAM technology and
      coded healing abutments. 

PMID- 24564615
TI  - An esthetic concern leads the way to improved oral health.
AB  - In order to make appropriate treatment decisions, clinicians must consider a
      patient's needs in total. As such, a systematic risk assessment is essential for
      developing a treatment plan that will both satisfy the patient's esthetic
      concerns and lower his or her risk for future problems. In this case, the
      patient's immediate concern was his smile, but he was unaware of the need for
      additional treatment, which included addressing occlusal dysfunction, extracting
      hopeless teeth and replacing them with an implant-retained prosthesis, and
      placement of indirect porcelain restorations. A comprehensive interdisciplinary
      approach between the clinician, implant surgeon, and laboratory was crucial for a
      successful outcome. 

PMID- 24564616
TI  - Hand hygiene in the dental setting: reducing the risk of infection.
AB  - Hand hygiene remains the single most important measure for reducing the risk of
      healthcare-associated infections. In the past 20 years, hand-washing
      recommendations and guidelines have become increasingly complex, and a plethora
      of products have become available. This article aims to discuss and clarify the
      fundamentals of appropriate hand hygiene in dentistry. 

PMID- 24564617
TI  - Dental implantology: an evolving treatment modality.
AB  - Diagnosis and treatment planning for dental implants has dramatically improved
      over the past three decades. Today's imaging technologies allow clinicians to
      assess individual patient-specific anatomy before the scalpel ever touches the
      patient. 

PMID- 24564618
TI  - Bioactive and therapeutic preventive approach to dental pit and fissure sealants.

PMID- 24564619
TI  - The influence of probiotics on zebrafish Danio rerio innate immunity and hepatic
      stress.
AB  - In this study, the effects of probiotic administration on zebrafish Danio rerio
      intestinal innate immunity and hepatic stress were evaluated. Zebrafish adults
      were treated for 10 days with the probiotic Lactobacillus rhamnosus IMC 501((r)).
      To assess the effects at the molecular level, the mRNA levels of genes involved
      in the innate immune system, stress response, oxidative stress, and apoptosis
      were quantified by real-time polymerase chain reaction. An increase of biomarkers
      related to innate immune responses was observed in intestinal tissue from the
      probiotic-treated fish compared with the control fish. In addition, a decrease in
      the abundance of stress and apoptotic-related genes was observed in the liver of
      the probiotic-fed fish. Finally, imaging Fourier transform infrared analysis was
      conducted on liver sections and the data obtained confirmed that probiotic
      administration decreased oxidative stress levels, decreased DNA damage, and
      increased lipid saturation levels. Overall, the results show that probiotic
      administration may enhance zebrafish welfare by modulating the innate immune
      response and improving hepatic stress tolerance.

PMID- 24564620
TI  - Statistics for approximate gene clusters.
AB  - BACKGROUND: Genes occurring co-localized in multiple genomes can be strong
      indicators for either functional constraints on the genome organization or
      remnant ancestral gene order. The computational detection of these patterns,
      which are usually referred to as gene clusters, has become increasingly sensitive
      over the past decade. The most powerful approaches allow for various types of
      imperfect cluster conservation: Cluster locations may be internally rearranged.
      The individual cluster locations may contain only a subset of the cluster genes
      and may be disrupted by uninvolved genes. Moreover cluster locations may not at
      all occur in some or even most of the studied genomes. The detection of such low
      quality clusters increases the risk of mistaking faint patterns that occur merely
      by chance for genuine findings. Therefore, it is crucial to estimate the
      significance of computational gene cluster predictions and discriminate between
      true conservation and coincidental clustering. RESULTS: In this paper, we present
      an efficient and accurate approach to estimate the significance of gene cluster
      predictions under the approximate common intervals model. Given a single gene
      cluster prediction, we calculate the probability to observe it with the same or a
      higher degree of conservation under the null hypothesis of random gene order, and
      add a correction factor to account for multiple testing. Our approach considers
      all parameters that define the quality of gene cluster conservation: the number
      of genomes in which the cluster occurs, the number of involved genes, the degree
      of conservation in the different genomes, as well as the frequency of the
      clustered genes within each genome. We apply our approach to evaluate gene
      cluster predictions in a large set of well annotated genomes.

PMID- 24564621
TI  - The effect of umbilical cord cleansing with chlorhexidine on omphalitis and
      neonatal mortality in community settings in developing countries: a meta
      analysis.
AB  - BACKGROUND: There is an increased risk of serious neonatal infection arising
      through exposure of the umbilical cord to invasive pathogen in home and facility
      births where hygienic practices are difficult to achieve. The World Health
      Organization currently recommends 'dry cord care' because of insufficient data in
      favor of or against topical application of an antiseptic. The primary objective
      of this meta-analysis is to evaluate the effects of application of chlorhexidine
      (CHX) to the umbilical cord to children born in low income countries on cord
      infection (omphalitis) and neonatal mortality. Standardized guidelines of Child
      Health Epidemiology Reference Group (CHERG) were followed to generate estimates
      of effectiveness of topical chlorhexidine application to umbilical cord for
      prevention of sepsis specific mortality, for inclusion in the Lives Saved Tool
      (LiST). METHODS: Systematic review and meta-analysis. Data sources included
      Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library,
      PubMed, CINHAL and WHO international clinical trials registry. Only randomized
      trials were included. Studies of children in hospital settings were excluded. The
      comparison group received no application to the umbilical cord (dry cord care),
      no intervention, or a non-CHX intervention. Primary outcomes were omphalitis and
      all-cause neonatal mortality. RESULTS: There were three cluster-randomised
      community trials (total participants 54,624) conducted in Nepal, Bangladesh and
      Pakistan that assessed impact of CHX application to the newborn umbilical cord
      for prevention of cord infection and mortality. Application of any CHX to the
      umbilical cord of the newborn led to a 23% reduction in all-cause neonatal
      mortality in the intervention group compared to control [RR 0.77, 95 % CI 0.63,
      0.94; random effects model, I2=50 %]. The reduction in omphalitis ranged from 27
      % to 56 % compared to control group depending on severity of infection. Based on
      CHERG rules, effect size for all-cause mortality was used for inclusion to LiST
      model as a proxy for sepsis specific mortality. CONCLUSIONS: Application of CHX
      to newborn umbilical cord can significantly reduce incidence of umbilical cord
      infection and all-cause mortality among home births in community settings. This
      inexpensive and simple intervention can save a significant number of newborn
      lives in developing countries.

PMID- 24564622
TI  - An inexpensive device to treat postpartum hemorrhage: a preliminary proof of
      concept study of health provider opinion and training in Nepal.
AB  - BACKGROUND: Obstetric hemorrhage remains the leading cause of maternal mortality
      in resource limited areas. An inexpensive pneumatic anti-shock garment was
      devised of bicycle tubes and tailored cloth which can be prepared from local
      materials in resource-limited settings. The main purposes of this study were: 1)
      to determine acceptability of the device by nurses and midwives and obtain
      suggestions for making the device more suitable for use in their particular work
      environments, 2) to determine whether a three hour training course provided
      adequate instruction in the use of this device for the application of
      circumferential abdominal pelvic pressure, and 3) determine production capability
      and cost in a resource-limited country. METHODS: Fifty-eight nurse and midwife
      participants took part in three sessions over eight months in Nepal. Correct
      device placement was assessed on non-pregnant participants using ultrasound
      measurement of distal aortic flow before and after device inflation, and analyzed
      using confidence intervals. Participants were surveyed to determine acceptability
      of the device, obtain suggestions for improvement, and to collect data on
      clinical use. RESULTS: Device placement achieved flow decreases with a mean of
      39% (95% CI 25%-53%, p < 0.001) in the first session, 28% (95% CI 21%-33%, P <
      0.001) after four months and 29% (95% CI 24%-34%, p < 0.001) at 8 months. All
      nurses and midwives thought the device would be acceptable for use in obstetric
      hemorrhage and that they could make, clean, and apply it. They quickly learned to
      apply the device, remembered how to apply it, and were willing and able to use
      the device clinically. Ten providers used the device, each on one patient, to
      treat obstetric hemorrhage after routine measures had failed; bleeding stopped
      promptly in all ten, two of whom were transported to the hospital. Production of
      devices in Kathmandu using local tailors and supplies cost approximately $40 per
      device, in a limited production setting. CONCLUSIONS: Preliminary data suggest
      that an inexpensive, easily-made device is potentially an appropriate addition to
      current obstetric hemorrhage treatment in resource-limited areas and that further
      study is warranted.

PMID- 24564623
TI  - Increased prevalence of early cochlear damage in young patients with type 1
      diabetes detected by distortion product otoacoustic emissions.
AB  - OBJECTIVE: To evaluate the hearing of adolescents with diabetes mellitus type
      1(DM1) by otoacoustic emissions (OAEs), and by comparing different tests with
      pure-tone audiometry to identify potential early cochlear impairments. DESIGN:
      Pure-tone audiometry, transient evoked otoacoustic emissions (TEOAEs), and
      distortion product otoacoustic emissions (DPOAEs) were performed in a group of
      adolescents with and without DM1. Clinical characteristics, disease duration, and
      glycated haemoglobin levels were studied. STUDY SAMPLE: Participants were 40
      adolescents with DM1 and 40 healthy subjects. RESULTS: Sensorineural hearing
      loss, affecting frequencies of 6000 and 8000 Hz, was found only in DM1 subjects
      when compared to the controls (7.7% vs. 0%, p < 0.05). A higher prevalence of
      cochlear damage was detected by DPOAE responses, 32% belonging from the diabetic
      group, vs. 3.7% in the control group. Absent TEOAE responses were observed in
      only three individuals, all from the diabetic group (5.1% of the tests performed
      in the diabetic group). Additionally, hearing thresholds were better in diabetic
      subjects with good control when compared to ones with regular or poor control (p
      = 0.00). Hearing thresholds were higher in poorly controlled diabetics when
      compared to subjects with good (p = 0.000) or regular control (p = 0.006).
      CONCLUSION: Early evidence of cochlear damage was detected in adolescents with
      DM1 leading to hearing loss at high frequencies. Abnormal DPOAEs responses were
      found more frequently than the alterations in TEOAEs and pure-tone audiometry,
      suggesting that DPOAEs evaluation is the most sensitive and it could be used for
      monitoring the progression of cochlear damage during the early stages of hearing
      impairment.

PMID- 24564624
TI  - Hearing threshold levels for a population of 11 to 35 year old Australian females
      and males.
AB  - OBJECTIVE: Detailed information on the hearing threshold levels (HTLs) of young
      Australians was gathered as part of a large-scale study of the relationship
      between HTL and leisure-noise exposure in young Australians. DESIGN: HTL data for
      the study population (18-35 year olds) was carefully collected, as well as
      otoscopy, tympanometry, contra-lateral acoustic reflexes, and otoacoustic
      emissions (transient and distortion product), together with a comprehensive
      hearing health history - both past and present. STUDY SAMPLE: The sample cohort
      consisted of 1407 individuals, females and males. RESULTS: Prior to analysis, HTL
      data were filtered according to both a 'Low' and 'High' set of exclusion
      criteria. The results obtained for both high-screen and low-screen datasets were
      around +5 dB above the traditionally accepted values of audiometric zero. This is
      consistent with previous published reports. CONCLUSION: Comparison with 'ISO 7029
      Acoustics: Statistical distribution of hearing thresholds as a function of age'
      indicated that threshold values for this dataset have a similar distribution to
      those of the Standard. This data provides a suitable reference HTL ('normative')
      database for young Australians.

PMID- 24564625
TI  - Comparison between hearing screening-detected cases and sporadic cases of delayed
      onset hearing loss in preschool-age children.
AB  - OBJECTIVE: This study aimed to compare the diagnosis and ages of intervention for
      cases of delayed-onset hearing loss identified sporadically or via a preschool
      hearing screening program. DESIGN: Retrospective study with the comparative
      analysis of two groups of children. STUDY SAMPLE: Cases identified from screening
      were selected from 34 321 preschool children who underwent screening for delayed
      onset hearing loss between October 2009 and May 2011. Sporadic cases of delayed
      onset hearing loss were selected from pediatric clinical records. Cases from the
      first group were excluded from the latter to avoid duplication. Two groups were
      given the same questionnaire to record risk indicators, diagnosis, and age at
      intervention. RESULTS: The average age of 26 children at the time of diagnosis in
      the screening group (52.81 +/- 13.23 months) was significantly earlier than in
      the 33 cases identified in the sporadic group (62.03 +/- 12.86 months; p < 0.05).
      The age at intervention of children with bilateral moderate to severe hearing
      loss in the screening group (50.40 +/- 10.76 months) was also earlier than in the
      sporadic group (62.73 +/- 13.77 months; p < 0.05). CONCLUSIONS: Improved rates of
      early diagnosis could therefore be achieved with hearing screening for preschool
      children with no significant symptoms of delayed-onset hearing loss.

PMID- 24564626
TI  - Rise/fall and plateau time optimization for cervical vestibular-evoked myogenic
      potential elicited by short tone bursts of 500 Hz.
AB  - OBJECTIVE: Literature on clinical utility of cervical vestibular-evoked myogenic
      potential (cVEMP) has been increasing rapidly, though not without inconsistencies
      in spite of involving similar populations. Close examination of methods across
      studies exposed the use of variable stimulus parameters, especially rise/fall
      time (R/FT) and plateau time (PT) as the possible reason. However the effect of
      variation in R/FT and PT on cVEMP response parameters has been largely uncharted.
      DESIGN: The study aimed at evaluating the impact of R/FT and PT on cVEMPs
      elicited by 500-Hz short tone-bursts (STBs) at 95 dB nHL using R/FT from 1 to 4
      ms and PT from 0 to 3 ms. STUDY SAMPLE: 30 healthy individuals with normal audio
      vestibular system. RESULTS: Significant prolongation of latencies with increasing
      R/FT and PT (p < 0.05) was noticed. The amplitude however varied significantly
      only for some R/FTs and PTs. R/FT of 2 ms, in combination with 1-ms PT, produced
      large amplitudes with lowest variability in amplitude and latency parameters.
      CONCLUSIONS: R/FT of 2 ms along with PT of 1 ms formed a good amalgamation and
      could be considered optimum for clinical recording of cVEMPs elicited by 500-Hz
      STBs, although slight deviances in these parameters might not impact the outcome
      significantly.

PMID- 24564628
TI  - Graphene oxide-based amplified fluorescent biosensor for Hg(2+) detection through
      hybridization chain reactions.
AB  - We report a graphene oxide (GO)-based fluorescent sensor for Hg(2+) detection in
      aqueous solutions by using hybridization chain reactions (HCRs). GO is used as an
      adsorption material for capturing single-stranded DNA and an efficient
      fluorescence quencher for reducing the background signal. In the detection
      strategy, two hairpin probes and a helper DNA are employed. Without Hg(2+), they
      are adsorbed by the GO and the fluorescence of one of the hairpin probes is
      quenched. In the presence of Hg(2+), the HCRs between the two hairpin probes are
      initiated by Hg(2+) with the aid of the helper DNA through T-Hg(2+)-T
      coordination chemistry. The double-stranded DNA products of the HCRs are released
      by the GO and the fluorescence is recovered. The detection limit of the sensing
      method is 0.3 nM, which is sufficiently sensitive for practical applications. The
      sensing system also exhibits high selectivity against other divalent metal ions,
      and the application of the sensor for drinking water shows that the proposed
      method works well for real samples. 

PMID- 24564627
TI  - A nucleosomal approach to inferring causal relationships of histone
      modifications.
AB  - MOTIVATION: Histone proteins are subject to various posttranslational
      modifications (PTMs). Elucidating their functional relationships is crucial
      toward understanding many biological processes. Bayesian network (BN)-based
      approaches have shown the advantage of revealing causal relationships, rather
      than simple cooccurrences, of PTMs. Previous works employing BNs to infer causal
      relationships of PTMs require that all confounders should be included. This
      assumption, however, is unavoidably violated given the fact that several
      modifications are often regulated by a common but unobserved factor. An existing
      non-parametric method can be applied to tackle the problem but the complexity and
      inflexibility make it impractical. RESULTS: We propose a novel BN-based method to
      infer causal relationships of histone modifications. First, from the evidence
      that nucleosome organization in vivo significantly affects the activities of PTM
      regulators working on chromatin substrate, hidden confounders of PTMs are
      selectively introduced by an information-theoretic criterion. Causal
      relationships are then inferred from a network model of both PTMs and the derived
      confounders. Application on human epigenomic data shows the advantage of the
      proposed method, in terms of computational performance and support from
      literature. Requiring less strict data assumptions also makes it more practical.
      Interestingly, analysis of the most significant relationships suggests that the
      proposed method can recover biologically relevant causal effects between histone
      modifications, which should be important for future investigation of histone
      crosstalk.

PMID- 24564629
TI  - Hydroxylation of organic polymer surface: method and application.
AB  - It may be hardly believable that inert C-H bonds on a polymeric material surface
      could be quickly and efficiently transformed into C-OH by a simple and mild way.
      Thanks to the approaches developed recently, it is now possible to transform
      surface H atoms of a polymeric substrate into monolayer OH groups by a
      simple/mild photochemical reaction. Herein the method and application of this
      small-molecular interfacial chemistry is highlighted. The existence of hydroxyl
      groups on material surfaces not only determines the physical and chemical
      properties of materials but also provides effective reaction sites for
      postsynthetic sequential modification to fulfill the requirements of various
      applications. However, organic synthetic materials based on petroleum, especially
      polyolefins comprise mainly C and H atoms and thus present serious surface
      problems due to low surface energy and inertness in reactivity. These limitations
      make it challenging to perform postsynthetic surface sequential chemical
      derivatization toward enhanced functionalities and properties and also cause
      serious interfacial problems when bonding or integrating polymer substrates with
      natural or inorganic materials. Polymer surface hydroxylation based on direct
      conversion of C-H bonds on polymer surfaces is thus of significant importance for
      academic and practical industrial applications. Although highly active research
      results have reported on small-molecular C-H bond activation in solution (thus
      homogeneous), most of them, featuring the use of a variety of transition metals
      as catalysts, present a slow reaction rate, a low atom economy and an obvious
      environmental pollution. In sharp contrast to these conventional C-H activation
      strategies, the present Spotlight describes a universal confined photocatalytic
      oxidation (CPO) system that is able to directly convert polymer surface C-H bonds
      to C-OSO3(-) and, subsequently, to C-OH through a simple hydrolysis. Generally
      speaking, these newly implanted hydroxyl groups preserve their own reactivity
      toward other complementary compounds, thus creating a novel base with distinct
      surface properties. Thanks to this functionalized platform, a wide range of
      organic, inorganic and metal materials have been attached to conventional organic
      polymer substrates through the rational engineering of surface molecular
      templates from small functional groups to macromolecules. It is expected that the
      proposed novel CPO method and its versatile usages in advanced material
      applications will offer new opportunities for a variety of scientific
      communities, especially for those working on surface/interface modulation. 

PMID- 24564630
TI  - Lipoprotein lipase activity is favoured by peritoneal dialysis compared to
      hemodialysis.
AB  - BACKGROUND: The lipoprotein lipase (LPL) pool is reduced by 50% in patients on
      hemodialysis (HD). LPL release by tinzaparin has not been investigated for
      peritoneal dialysis (PD). Therefore, the aim of this study was to investigate if
      tinzaparin differently alters the pool of LPL and triglyceride levels of patients
      on HD versus PD. MATERIALS AND METHODS: Thirty-two patients on chronic PD or HD
      were matched to nearest age and gender. In order to release and thereby estimate
      the endothelial pool of LPL, all patients received a bolus of tinzaparin (75
      units/kg). Blood samples were drawn for analysis of LPL activity and
      triglycerides (TG) between the groups. RESULTS: The peak level of LPL released at
      40 min after tinzaparin was similar in PD and HD patients. At 180 min, a slightly
      higher median level of LPL activity was noted in the PD patients (6.1 mU/mL (n =
      6) versus 3.4 mU/mL (n = 16), p = 0.005). The TG concentration in plasma at 40
      min was reduced relatively more in the PD patients than in the HD patients (p <
      0.05). At 180 min, TG had returned to start levels in HD patients while they were
      still lowered in PD patients. CONCLUSIONS: The negative effect of uraemia on the
      LPL pool in HD patients, known from other studies, here is shown to be similar in
      PD patients. Tinzaparin administration releases the LPL pool during each HD but
      does not cause an exhaustion of the LPL system over time. In contrast to HD, the
      LPL pool is not altered during PD.

PMID- 24564631
TI  - Adipocytokine concentrations in children with different types of beta
      thalassemia.
AB  - BACKGROUND: Beta-thalassemia is an inherited blood disorder. It results from the
      impaired production of beta-globin chains, leading to a relative excess of alpha
      globin chains. Clinical severity separates this disease into three main subtypes:
      beta- thalassemia major, beta-thalassemia intermedia and beta-thalassemia minor,
      the former two being clinically more significant. Inflammatory processes may play
      an important role in some of the complications of thalassemia. Adipose tissue is
      one of the most important endocrine and secretory organs that release
      adipocytokines like adiponectin, resistin and visfatin. AIM: The aim of our study
      was to analyze adipocytokine concentrations (adiponectin, resistin and visfatin)
      in different types of beta-thalassemia patients and determine any possible
      correlations with disease severity. METHODS: We recruited 29 patients who were
      transfusion-dependent beta-thalassemia-major patients, 17 patients with beta
      thalassemia intermedia, 30 beta-thalassemia minor patients. The control group
      consisted of 30 healthy children. Anthropometric measurements, complete blood
      count, biochemical parameters, serum concentrations of adiponectin, resistin,
      visfatin were performed for all subjects. RESULTS: Resistin and visfatin
      concentrations were significantly higher in beta-thalassemia minor patients than
      in controls. Adiponetin, resistin and visfatin concentrations were significantly
      higher in both beta-thalassemia intermedia and major patients than in controls.
      The concentrations of adiponectin, resistin and visfatin were significantly
      higher in both beta-thalassemia intermedia and major patients than in beta
      thalassemia minor patients. There was no significant difference between beta
      thalassemia intermedia and beta-thalassemia major patients for adipocytokines
      concentrations. CONCLUSION: We speculate that these adipocytokines may play a
      role in the development of complications in beta-thalassaemia.

PMID- 24564632
TI  - Natriuretic peptides in the evaluation of syncope in children and adolescents.
AB  - INTRODUCTION: Natriuretic peptides have an increasing role in assessing
      cardiovascular conditions. The number of papers addressing their role in the
      evaluation of children with syncope of unclear etiology is sparse. The aim of
      this study was to determine whether measuring atrial natriuretic peptide (ANP)
      and the inactive form, N-terminal prohormone of brain natriuretic peptide (NT
      proBNP) concentration in children admitted due to differential diagnosis of
      syncope can be helpful in establishing the most probable cause of this condition.
      METHODS: The study included 88 patients between 9 and 18 years of age
      hospitalized due to syncope. The control group comprised 25 healthy children. In
      order to identify the cause of syncope, children with this condition were
      subjected to cardiologic and neurologic evaluation, and ANP and NT-proBNP
      concentrations were determined. RESULTS: The syncope group and the controls did
      not differ significantly in terms of natriuretic peptides concentrations.
      Similarly, no significant intergroup differences in natriuretic peptide
      concentrations were documented between children representing various types of
      response to the tilt test, and between the subgroups of patients with syncope of
      various origins. CONCLUSION: Analysis of natriuretic peptides concentrations in
      children with syncope does not result in unambiguous findings that would enable
      establishing accurate diagnosis.

PMID- 24564633
TI  - Association of alkaline phosphatase with isolated coronary artery ectasia.
AB  - BACKGROUND: It has been shown that alkaline phosphatase (ALP) is a reliable
      marker for cardiovascular events and mortality. However, there is no data
      available regarding the association of ALP with isolated coronary artery ectasia
      (CAE). The aim of the present study was to assess the serum ALP activity in
      isolated CAE. METHODS: Seventy-nine patients with isolated CAE (59 males; mean
      age, 52 +/- 12 years) and 88 age- and gender-matched normal subjects (73 males;
      mean age, 52 +/- 7 years) were enrolled. Baseline characteristics were recorded
      in both groups and serum ALP activity were compared between the two groups.
      RESULTS: Patients with angiography-proved isolated CAE had significantly higher
      serum ALP activity compared with angiographic normal controls (72.41 +/- 29.97
      vs. 59.27 +/- 14.46, p < 0.001). In the multivariate analysis, increased ALP (OR
      = 1.037, 95% CI 1.017-1.057, p < 0.001) were independent predictors for the
      presence of isolated CAE. A cut-off of >= 66.5 U/L of ALP activity measured on
      admission had a 60.8% sensitivity and 75.0% specificity in predicting isolated
      CAE by receiver operating characteristic (ROC) curve analysis. CONCLUSION: Our
      data firstly demonstrated that serum ALP activity, a readily available clinical
      laboratory value, was associated with the presence of isolated CAE.

PMID- 24564634
TI  - Comparison of atorvastatin, pitavastatin and rosuvastatin for residual
      cardiovascular risk using non-fasting blood sampling.
AB  - BACKGROUND: Low-density lipoprotein cholesterol (LDL-C) is a major cardiovascular
      risk. However, some patients show symptoms of coronary heart disease (CHD) even
      though their LDL-C is strictly controlled. Therefore, it is important to treat
      other risk factors. METHODS: Some 129 outpatients with dyslipidemia who were
      treated with either atorvastatin 10 mg/day (ATO), pitavastatin 2 mg/day (PIT), or
      rosuvastatin 2.5 mg/day (ROS) were enrolled. After informed consent was obtained,
      these patients were switched to another statin. Lipid profiles and lipoprotein
      fraction by polyacrylamide gel electrophoresis (PAGE) were compared between
      before and after 3 months of treatment with non-fasting blood sample. RESULTS:
      LDL-C did not show any significant changes after switching and was maintained
      around 2.59 mmol/L in all groups. High-density lipoprotein cholesterol (HDL-C)
      was significantly increased in group ATO->PIT (1.43->1.54 mmol/L, p = 0.0010) and
      ROS->PIT (1.46->1.57 mmol/L, p = 0.0004), and was significantly decreased in
      group PIT->ATO (1.44->1.36 mmol/L, p = 0.0290). Apolipoprotein A-I (Apo A-I) and
      preheparin lipoprotein lipase (LPL) mass showed similar changes in HDL-C. Changes
      in HDL-C showed a significant positive correlation with those in Apo A-I and
      preheparin LPL mass, and a little but significant negative correlation with
      changes in Lp(a) and intermediate density lipoprotein (IDL) fraction.
      CONCLUSIONS: ATO, PIT, and ROS have comparable effect on LDL-C lowering. Changes
      in HDL-C were similar to those in Apo A-I and preheparin LPL mass, and PIT was
      the most effective treatment in increasing HDL-C, Apo A-I, and preheparin LPL
      mass.

PMID- 24564635
TI  - NETTAB 2012 on "Integrated Bio-Search".
AB  - The NETTAB 2012 workshop, held in Como on November 14-16, 2012, was devoted to
      "Integrated Bio-Search", that is to technologies, methods, architectures, systems
      and applications for searching, retrieving, integrating and analyzing data,
      information, and knowledge with the aim of answering complex bio-medical
      molecular questions, i.e. some of the most challenging issues in bioinformatics
      today. It brought together about 80 researchers working in the field of
      Bioinformatics, Computational Biology, Biology, Computer Science and Engineering.
      More than 50 scientific contributions, including keynote and tutorial talks, oral
      communications, posters and software demonstrations, were presented at the
      workshop. This preface provides a brief overview of the workshop and shortly
      introduces the peer-reviewed manuscripts that were accepted for publication in
      this Supplement. 

PMID- 24564636
TI  - Predicting mild traumatic brain injury patients at risk of persistent symptoms in
      the Emergency Department.
AB  - OBJECTIVE: To identify factors that can predict which emergency department (ED)
      patients with mTBI are likely to develop persistent post-concussion symptoms
      (PPCS). DESIGN: A matched case-control study was conducted at a Level 1 trauma
      centre between June 2006 and July 2009. Patients diagnosed with mTBI in the ED
      and diagnosed at a concussion management programme with at least one PPCS (85
      cases) were compared to patients diagnosed with mTBI in the ED (340 controls) to
      determine if factors assessed at the time of ED presentation could predict
      patients likely to develop persistent symptoms. RESULTS: Multivariable
      hierarchical logistic regression with variables indicating increased risk for
      PPCS (prior mTBI, history of depression, history of anxiety, multiple injury,
      forgetfulness/poor memory, noise sensitivity, or light sensitivity) resulted in a
      final predictive model including prior mTBI, history of anxiety,
      forgetfulness/poor memory and light sensitivity. The final model had a
      specificity of 87.9% and a sensitivity of 69.9%. CONCLUSIONS: A strong prediction
      model to identify those ED patients with mTBI at risk for PPCS was developed and
      could be easily implemented in the ED; therefore, helping to target those
      patients who would potentially benefit from close follow-up.

PMID- 24564637
TI  - Molecular pathway identification using biological network-regularized logistic
      models.
AB  - BACKGROUND: Selecting genes and pathways indicative of disease is a central
      problem in computational biology. This problem is especially challenging when
      parsing multi-dimensional genomic data. A number of tools, such as L1-norm based
      regularization and its extensions elastic net and fused lasso, have been
      introduced to deal with this challenge. However, these approaches tend to ignore
      the vast amount of a priori biological network information curated in the
      literature. RESULTS: We propose the use of graph Laplacian regularized logistic
      regression to integrate biological networks into disease classification and
      pathway association problems. Simulation studies demonstrate that the performance
      of the proposed algorithm is superior to elastic net and lasso analyses. Utility
      of this algorithm is also validated by its ability to reliably differentiate
      breast cancer subtypes using a large breast cancer dataset recently generated by
      the Cancer Genome Atlas (TCGA) consortium. Many of the protein-protein
      interaction modules identified by our approach are further supported by evidence
      published in the literature. Source code of the proposed algorithm is freely
      available at http://www.github.com/zhandong/Logit-Lapnet. CONCLUSION: Logistic
      regression with graph Laplacian regularization is an effective algorithm for
      identifying key pathways and modules associated with disease subtypes. With the
      rapid expansion of our knowledge of biological regulatory networks, this approach
      will become more accurate and increasingly useful for mining transcriptomic, epi
      genomic, and other types of genome wide association studies.

PMID- 24564638
TI  - A computational pipeline for identifying kinetic motifs to aid in the design and
      improvement of synthetic gene circuits.
AB  - BACKGROUND: An increasing number of genetic components are available in several
      depositories of such components to facilitate synthetic biology research, but
      picking out those that will allow a designed circuit to achieve the specified
      function still requires multiple cycles of testing. Here, we addressed this
      problem by developing a computational pipeline to mathematically simulate a gene
      circuit for a comprehensive range and combination of the kinetic parameters of
      the biological components that constitute the gene circuit. RESULTS: We showed
      that, using a well-studied transcriptional repression cascade as an example, the
      sets of kinetic parameters that could produce the specified system dynamics of
      the gene circuit formed clusters of recurrent combinations, referred to as
      kinetic motifs, which appear to be associated with both the specific topology and
      specified dynamics of the circuit. Furthermore, the use of the resulting
      "handbook" of performance-ranked kinetic motifs in finding suitable circuit
      components was illustrated in two application scenarios. CONCLUSIONS: These
      results show that the computational pipeline developed here can provide a
      rational-based guide to aid in the design and improvement of synthetic gene
      circuits.

PMID- 24564641
TI  - Optical coherence tomography features of POEMS syndrome and Castleman disease
      associated papillopathy.
AB  - PURPOSE: To report ocular symptoms and optical coherence tomography (OCT)
      features of polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy,
      and skin changes (POEMS) syndrome. METHODS: Case report of two Caucasian patients
      with POEMS, one of whom also had multicentric Castleman disease. RESULTS: Both
      patients presented with edema on both optic disks, bilateral macular edema was
      seen in case 1, and peripapillary choroidal neovascularization was seen on the
      right side in case 2. OCT confirmed papilledema involving all retinal layers,
      with additional bilateral peripapillary serous retinal detachment involving the
      macula in both cases, and peripapillary CNV in case 2. Changes in retinal nerve
      fiber layer thickness, total peripapillary retinal thickness, and macular
      detachment were followed with OCT over the course of the disease and after
      administration of systemic therapy. CONCLUSION: OCT examination of the optic
      nerve head and the macula has an important additional role in the diagnosis and
      follow-up of POEMS syndrome and Castleman disease.

PMID- 24564639
TI  - Relationship between modeling technique and reported outcomes: case studies in
      models for the treatment of schizophrenia.
AB  - Complex modeling techniques such as discrete-event simulation and simpler Markov
      or decision-tree models have been used to estimate the cost-effectiveness of
      treatment for chronic diseases such as schizophrenia. A systematic literature
      review of MEDLINE, EconLit, Embase, and the Cochrane Library identified
      schizophrenia modeling studies presenting incremental cost-effectiveness ratios.
      The relationship between modeling technique used and reported outcomes was
      examined. Fifty-four studies reporting results of 69 pairs of drug comparisons
      were identified. Of the paired-drug comparisons, 27 were conducted in at least
      two studies; in 14 of the 27, the results agreed (i.e., drug A cost-effective
      compared with drug B) despite differences in modeling techniques. Thirteen of the
      27 paired-drug comparisons had contradictory study results even when the same
      modeling technique was used. Different modeling techniques did not appear to
      explain different findings about cost-effectiveness. 

PMID- 24564642
TI  - Residual confounding explains the association between high parity and child
      mortality.
AB  - BACKGROUND: This study used data from recent Demographic and Health Surveys (DHS)
      to examine the impact of high parity on under-five and neonatal mortality. The
      analyses used various techniques to attempt eliminating selection issues,
      including stratification of analyses by mothers' completed fertility. METHODS: We
      analyzed DHS datasets from 47 low- and middle-income countries. We only used data
      from women who were age 35 or older at the time of survey to have a measure of
      their completed fertility. We ran log-binominal regression by country to
      calculate relative risk between parity and both under-five and neonatal
      mortality, controlled for wealth quintile, maternal education, urban versus rural
      residence, maternal age at first birth, calendar year (to control for possible
      time trends), and birth interval. We then controlled for maternal background
      characteristics even further by using mothers' completed fertility as a proxy
      measure. RESULTS: We found a statistically significant association between high
      parity and child mortality. However, this association is most likely not
      physiological, and can be largely attributed to the difference in background
      characteristics of mothers who complete reproduction with high fertility versus
      low fertility. Children of high completed fertility mothers have statistically
      significantly increased risk of death compared to children of low completed
      fertility mothers at every birth order, even after controlling for available
      confounders (i.e. among children of birth order 1, adjusted RR of under-five
      mortality 1.58, 95% CI: 1.42, 1.76). There appears to be residual confounders
      that put children of high completed fertility mothers at higher risk, regardless
      of birth order. When we examined the association between parity and under-five
      mortality among mothers with high completed fertility, it remained statistically
      significant, but negligible in magnitude (i.e. adjusted RR of under-five
      mortality 1.03, 95% CI: 1.02-1.05). CONCLUSIONS: Our analyses strongly suggest
      that the observed increased risk of mortality associated with high parity births
      is not driven by a physiological link between parity and mortality. We found that
      at each birth order, children born to women who have high fertility at the end of
      their reproductive period are at significantly higher mortality risk than
      children of mothers who have low fertility, even after adjusting for available
      confounders. With each unit increase in birth order, a larger proportion of
      births at the population level belongs to mothers with these adverse
      characteristics correlated with high fertility. Hence it appears as if mortality
      rates go up with increasing parity, but not for physiological reasons.

PMID- 24564644
TI  - Disentangling homeologous contigs in allo-tetraploid assembly: application to
      durum wheat.
AB  - BACKGROUND: Using Next Generation Sequencing, SNP discovery is relatively easy on
      diploid species and still hampered in polyploid species by the confusion due to
      homeology. We develop HomeoSplitter; a fast and effective solution to split
      original contigs obtained by RNAseq into two homeologous sequences. It uses the
      differential expression of the two homeologous genes in the RNA. We verify that
      the new sequences are closer to the diploid progenitors of the allopolyploid
      species than the original contig. By remapping original reads on these new
      sequences, we also verify that the number of valuable detected SNPs has
      significantly increased. RESULTS: HomeoSplitter is a fast and effective solution
      to disentangle homeologous sequences based on a maximum likelihood optimization.
      On a benchmark set of 2,505 clusters containing homologous sequences of urartu,
      speltoides and durum, HomeoSplitter was efficient to build sequences closer to
      the diploid references and increased the number of valuable SNPs from 188 out of
      1,360 SNPs detected when mapping the reads on the de novo durum assembly to 762
      out of 1,620 SNPs when mapping on HomeoSplitter contigs. CONCLUSIONS: The
      HomeoSplitter program is freely available at
      http://bioweb.supagro.inra.fr/homeoSplitter/. This work provides a practical
      solution to the complex problem of disentangling homeologous transcripts in allo
      tetraploids, which further allows an improved SNP detection.

PMID- 24564645
TI  - Nasal carriage of methicillin resistant staphylococci.
AB  - Coagulase-negative staphylococci (CoNS) are believed to function as reservoirs,
      as well as possible sources of staphylococcal chromosome cassette mec (SCCmec) to
      Staphylococcus aureus, but the frequency, preferred partners, and factors
      promoting SCCmec transfer are not known. Such postulated in vivo genetic transfer
      events are likely to occur at anatomical sites such as the normal nasal mucosa,
      which is known to be colonized by both CoNS and coagulase positive staphylococci.
      In this study, we characterized S. aureus and CoNS strains colonizing the
      anterior nares of 67 patients in Denmark. A total of 54 patients (80%) were
      colonized with staphylococci that included nine different species identified by
      internal transcribed spacer PCR (ITS-PCR) and 16S RNA sequencing. The highest
      rates of colonization were found for S. epidermidis (58%) and S. aureus (39%).
      Methicillin resistance was present in S. aureus (53%), S. epidermidis (53%), S.
      haemolyticus (33%), and S. hominis (62%). Genetic backgrounds were characterized
      by spa typing for S. aureus and by pulsed-field gel electrophoresis for CoNS.
      SCCmec typing showed that SCCmec type IV (2B) was the most common in the entire
      collection (65%). Carriage of multiple species was detected in 20 patients (30%),
      16 of whom were colonized with both S. aureus and S. epidermidis. In two cases,
      simultaneous carriage of different methicillin resistant species was detected.
      However, the strains carried different SCCmec types. Additional studies in the
      same epidemiological settings are warranted to identify interspecific genetic
      events that involve the acquisition of SCCmec by S. aureus. 

PMID- 24564643
TI  - Polarizable empirical force field for hexopyranose monosaccharides based on the
      classical Drude oscillator.
AB  - A polarizable empirical force field based on the classical Drude oscillator is
      presented for the hexopyranose form of selected monosaccharides. Parameter
      optimization targeted quantum mechanical (QM) dipole moments, solute-water
      interaction energies, vibrational frequencies, and conformational energies.
      Validation of the model was based on experimental data on crystals, densities of
      aqueous-sugar solutions, diffusion constants of glucose, and rotational
      preferences of the exocylic hydroxymethyl of d-glucose and d-galactose in aqueous
      solution as well as additional QM data. Notably, the final model involves a
      single electrostatic model for all sixteen diastereomers of the monosaccharides,
      indicating the transferability of the polarizable model. The presented parameters
      are anticipated to lay the foundation for a comprehensive polarizable force field
      for saccharides that will be compatible with the polarizable Drude parameters for
      lipids and proteins, allowing for simulations of glycolipids and glycoproteins. 

PMID- 24564646
TI  - Systematic review of probiotics for the treatment of community-acquired acute
      diarrhea in children.
AB  - BACKGROUND: Oral rehydration salts (ORS), zinc, and continued feeding are the
      recommended treatments for community-acquired acute diarrhea among young
      children. However, probiotics are becoming increasingly popular treatments for
      diarrhea in some countries. We sought to estimate the effect of probiotics on
      diarrhea morbidity and mortality in children < 5 years of age. METHODS: We
      conducted a systematic review of randomized controlled trials to estimate the
      effect of probiotic microorganisms for the treatment of community-acquired acute
      diarrhea in children. Data were abstracted into a standardized table and study
      quality was assessed using the Child Health Epidemiology Reference Group (CHERG)
      adaption of the GRADE technique. We measured the relative effect of probiotic
      treatment in addition to recommended rehydration on hospitalizations, duration
      and severity. We then calculated the average percent difference for all
      continuous outcomes and performed a meta-analysis for discrete outcomes. RESULTS:
      We identified 8 studies for inclusion in the final database. No studies reported
      diarrhea mortality and overall the evidence was low to moderate quality.
      Probiotics reduced diarrhea duration by 14.0% (95% CI: 3.8-24.2%) and stool
      frequency on the second day of treatment by 13.1% (95% CI: 0.8 - 25.3%). There
      was no effect on the risk of diarrhea hospitalizations. CONCLUSION: Probiotics
      may be efficacious in reducing diarrhea duration and stool frequency during a
      diarrhea episode. However, only few studies have been conducted in low-income
      countries and none used zinc (the current recommendation) thus additional
      research is needed to understand the effect of probiotics as adjunct therapy for
      diarrhea among children in developing countries.

PMID- 24564647
TI  - Extracting rate changes in transcriptional regulation from MEDLINE abstracts.
AB  - BACKGROUND: Time delays are important factors that are often neglected in gene
      regulatory network (GRN) inference models. Validating time delays from knowledge
      bases is a challenge since the vast majority of biological databases do not
      record temporal information of gene regulations. Biological knowledge and facts
      on gene regulations are typically extracted from bio-literature with specialized
      methods that depend on the regulation task. In this paper, we mine evidences for
      time delays related to the transcriptional regulation of yeast from the PubMed
      abstracts. RESULTS: Since the vast majority of abstracts lack quantitative time
      information, we can only collect qualitative evidences of time delays.
      Specifically, the speed-up or delay in transcriptional regulation rate can
      provide evidences for time delays (shorter or longer) in GRN. Thus, we focus on
      deriving events related to rate changes in transcriptional regulation. A corpus
      of yeast regulation related abstracts was manually labeled with such events. In
      order to capture these events automatically, we create an ontology of sub
      processes that are likely to result in transcription rate changes by combining
      textual patterns and biological knowledge. We also propose effective feature
      extraction methods based on the created ontology to identify the direct evidences
      with specific details of these events. Our ontologies outperform existing state
      of-the-art gene regulation ontologies in the automatic rule learning method
      applied to our corpus. The proposed deterministic ontology rule-based method can
      achieve comparable performance to the automatic rule learning method based on
      decision trees. This demonstrates the effectiveness of our ontology in
      identifying rate-changing events. We also tested the effectiveness of the
      proposed feature mining methods on detecting direct evidence of events.
      Experimental results show that the machine learning method on these features
      achieves an F1-score of 71.43%. CONCLUSIONS: The manually labeled corpus of
      events relating to rate changes in transcriptional regulation for yeast is
      available in https://sites.google.com/site/wentingntu/data. The created
      ontologies summarized both biological causes of rate changes in transcriptional
      regulation and corresponding positive and negative textual patterns from the
      corpus. They are demonstrated to be effective in identifying rate-changing
      events, which shows the benefits of combining textual patterns and biological
      knowledge on extracting complex biological events.

PMID- 24564649
TI  - Facile bottom-up synthesis of coronene-based 3-fold symmetrical and highly
      substituted nanographenes from simple aromatics.
AB  - A facile and efficient self-sorting assemble (CSA) strategy has been paved for
      bottom-up construction of the 3-fold symmetrical and highly substituted hexa-cata
      hexabenzocoronenes (c-HBCs), the trithieno analogues, and larger disc-shaped PAHs
      from simple chemicals using benzylic carbons as tenon joints and a novel FeCl3
      mediated AAA process as a key step. The structures of the as-prepared c-HBCs and
      related NGs were clearly identified by spectral analyses and X-ray
      crystallographic studies. Moreover, these can be envisaged to serve as new
      launching platforms for the construction of larger and more complex pi-conjugated
      molecules and supramolecular architectures because of the modifiable and
      symmetrical decorations. 

PMID- 24564650
TI  - Yet another decennium of the Institute of Physiology: a dynamic interplay of
      innovative approaches and 60 years of tradition.
AB  - I am pleased to introduce this special issue of Physiological Research published
      on the occasion of the 60th anniversary of the Institute of Physiology. It is
      only a second issue of this kind, the previous one being Physiological Research
      53 (Suppl. 1) 2004. Since then, the Institute contributed its expertise to modern
      fields of physiology such as cardiovascular physiology, neurophysiology, energy
      metabolism, membrane transport, chronobiology, as well as relevant methodology.
      Diverse local and international collaboration has augmented such effort, as
      summarized in the attached Synopsis outlining the most significant achievements
      of Institute's departments during the past ten years. I very much hope that
      achievements of this kind will become Institute's tradition justifying at least
      equally optimistic forthcoming special issues in the decades to come. 

PMID- 24564651
TI  - Recent progress in the genetics of spontaneously hypertensive rats.
AB  - The spontaneously hypertensive rat (SHR) is the most widely used animal model of
      essential hypertension and accompanying metabolic disturbances. Recent advances
      in sequencing of genomes of BN-Lx and SHR progenitors of the BXH/HXB recombinant
      inbred (RI) strains as well as accumulation of multiple data sets of intermediary
      phenotypes in the RI strains, including mRNA and microRNA abundance, quantitative
      metabolomics, proteomics, methylomics or histone modifications, will make it
      possible to systematically search for genetic variants involved in regulation of
      gene expression and in the etiology of complex pathophysiological traits. New
      advances in manipulation of the rat genome, including efficient transgenesis and
      gene targeting, will enable in vivo functional analyses of selected candidate
      genes to identify QTL at the molecular level or to provide insight into
      mechanisms whereby targeted genes affect pathophysiological traits in the SHR. 

PMID- 24564648
TI  - A comparison of electrospun polymers reveals poly(3-hydroxybutyrate) fiber as a
      superior scaffold for cardiac repair.
AB  - The development of biomaterials for myocardial tissue engineering requires a
      careful assessment of their performance with regards to functionality and
      biocompatibility, including the immune response. Poly(3-hydroxybutyrate) (PHB),
      poly(e-caprolactone) (PCL), silk, poly-lactic acid (PLA), and polyamide (PA)
      scaffolds were generated by electrospinning, and cell compatibility in vitro, and
      immune response and cardiac function in vitro and in vivo were compared with a
      noncrosslinked collagen membrane (Col) control material. Results showed that cell
      adhesion and growth of mesenchymal stem cells, cardiomyocytes, and cardiac
      fibroblasts in vitro was dependent on the polymer substrate, with PHB and PCL
      polymers permitting the greatest adhesion/growth of cells. Additionally, polymer
      substrates triggered unique expression profiles of anti- and pro-inflammatory
      cytokines in human peripheral blood mononuclear cells. Implantation of PCL, silk,
      PLA, and PA patches on the epicardial surface of healthy rats induced a classical
      foreign body reaction pattern, with encapsulation of polymer fibers and induction
      of the nonspecific immune response, whereas Col and PHB patches were
      progressively degraded. When implanted on infarcted rat heart, Col, PCL, and PHB
      reduced negative remodeling, but only PHB induced significant angiogenesis.
      Importantly, Col and PHB modified the inflammatory response to an M2 macrophage
      phenotype in cardiac tissue, indicating a more beneficial reparative process and
      remodeling. Collectively, these results identify PHB as a superior substrate for
      cardiac repair. 

PMID- 24564652
TI  - Effects of long-term thyroid hormone level alterations, n-3 polyunsaturated fatty
      acid supplementation and statin administration in rats.
AB  - Thyroid hormones (THs) play multiple roles in the organism and alterations of
      their levels can result in many pathological changes. Currently, we use
      hyperthyroid and hypothyroid rats as "models of a diseased organism" and analyze
      whether n-3 polyunsaturated fatty acids (n-3 PUFA) administration can ameliorate
      TH-induced pathophysiological changes. We investigate myosin heavy chain
      composition, calsequestrin levels, changes in cardiac tissue remodeling and cell
      to-cell communication, expression of protein kinases, mitochondrial functions,
      oxidative stress markers and cell death, changes in serum lipid levels,
      activities of key enzymes of thyroid hormone metabolism, activity of
      acetylcholine esterase and membrane anisotropy, as well as mobile behavior and
      thermal sensitivity. Additionally we also mention our pilot experiments dealing
      with the effect of statin administration on skeletal muscles and sensory
      functions. As THs and n-3 PUFA possess multiple sites of potential action, we
      hope that our complex research will contribute to a better understanding of their
      actions, which can be useful in the treatment of different pathophysiological
      events including cardiac insufficiency in humans. 

PMID- 24564653
TI  - Development of radiometric assays for quantification of enzyme activities of the
      key enzymes of thyroid hormones metabolism.
AB  - We newly elaborated and adapted several radiometric enzyme assays for the
      determination of activities of the key enzymes engaged in the biosynthesis
      (thyroid peroxidase, TPO) and metabolic transformations (conjugating enzymes and
      iodothyronine deiodinases, IDs) of thyroid hormones (THs) in the thyroid gland
      and in peripheral tissues, especially in white adipose tissue (WAT). We also
      elaborated novel, reliable radiometric methods for extremely sensitive
      determination of enzyme activities of IDs of types 1, 2 and 3 in microsomal
      fractions of different rat and human tissues, as well as in homogenates of
      cultured mammalian cells. The use of optimized TLC separation of radioactive
      products from the unconsumed substrates and film-less autoradiography of
      radiochromatograms, taking advantage of storage phosphor screens, enabled us to
      determine IDs enzyme activities as low as 10(-18) katals. In studies of the
      interaction of fluoxetine (Fluox) with the metabolism of THs, we applied adapted
      radiometric enzyme assays for iodothyronine sulfotransferases (ST) and uridine 5'
      diphospho-glucuronyltransferase (UDP-GT). Fluox is the most frequently used
      representative of a new group of non-tricyclic antidepressant drugs--selective
      serotonin re-uptake inhibitors. We used the elaborated assays for quantification
      the effects of Fluox and for the assessment of the degree of potential induction
      of rat liver ST and/or UDP-GT enzyme activities by Fluox alone or in combination
      with T(3). Furthermore, we studied possible changes in IDs activities in murine
      adipose tissue under the conditions that promoted either tissue hypertrophy
      (obesogenic treatment) or involution (caloric restriction), and in response to
      leptin, using our newly developed radiometric enzyme assays for IDs. Our results
      suggest that deiodinase D1 has a functional role in WAT, with D1 possibly being
      involved in the control of adipose tissue metabolism and/or accumulation of the
      tissue. Significant positive correlation between specific enzyme activity of D1
      in WAT and plasma leptin levels was found. The newly developed and adapted
      radiometric enzyme assays proved to be very useful tools for studies of factors
      modulating THs metabolism, not only in model animals but also in clinical studies
      of human obesity.

PMID- 24564654
TI  - Proteomics of human teeth and saliva.
AB  - Teeth have been a focus of interest for many centuries--due to medical problems
      with them. They are the hardest part of the human body and are composed of three
      mineralized parts--enamel, dentin and cementum, together with the soft pulp.
      However, saliva also has a significant impact on tooth quality. Proteomic
      research of human teeth is now accelerating, and it includes all parts of the
      tooth. Some methodological problems still need to be overcome in this research
      field--mainly connected with calcified tissues. This review will provide an
      overview of the current state of research with focus on the individual parts of
      the tooth and pellicle layer as well as saliva. These proteomic results can help
      not only stomatology in terms of early diagnosis, identifying risk factors, and
      systematic control.

PMID- 24564655
TI  - Mechanisms of the 14-3-3 protein function: regulation of protein function through
      conformational modulation.
AB  - Many aspects of protein function regulation require specific protein-protein
      interactions to carry out the exact biochemical and cellular functions. The
      highly conserved members of the 14-3-3 protein family mediate such interactions
      and through binding to hundreds of other proteins provide multitude of regulatory
      functions, thus playing key roles in many cellular processes. The 14-3-3 protein
      binding can affect the function of the target protein in many ways including the
      modulation of its enzyme activity, its subcellular localization, its structure
      and stability, or its molecular interactions. In this minireview, we focus on
      mechanisms of the 14-3-3 protein-dependent regulation of three important 14-3-3
      binding partners: yeast neutral trehalase Nth1, regulator of G-protein signaling
      3 (RGS3), and phosducin. 

PMID- 24564656
TI  - Opioid-receptor (OR) signaling cascades in rat cerebral cortex and model cell
      lines: the role of plasma membrane structure.
AB  - Large number of extracellular signals is received by plasma membrane receptors
      which, upon activation, transduce information into the target cell interior via
      trimeric G-proteins (GPCRs) and induce activation or inhibition of adenylyl
      cyclase enzyme activity (AC). Receptors for opioid drugs such as morphine (micro
      OR, delta-OR and kappa-OR) belong to rhodopsin family of GPCRs. Our recent
      results indicated a specific up-regulation of AC I (8-fold) and AC II (2.5-fold)
      in plasma membranes (PM) isolated from rat brain cortex exposed to increasing
      doses of morphine (10-50 mg/kg) for 10 days. Increase of ACI and ACII represented
      the specific effect as the amount of ACIII-ACIX, prototypical PM marker Na, K
      ATPase and trimeric G-protein alpha and beta subunits was unchanged. The up
      regulation of ACI and ACII faded away after 20 days since the last dose of
      morphine. Proteomic analysis of these PM indicated that the brain cortex of
      morphine-treated animals cannot be regarded as being adapted to this drug because
      significant up-regulation of proteins functionally related to oxidative stress
      and alteration of brain energy metabolism occurred. The number of delta-OR was
      increased 2-fold and their sensitivity to monovalent cations was altered.
      Characterization of delta-OR-G-protein coupling in model HEK293 cell line
      indicated high ability of lithium to support affinity of delta-OR response to
      agonist stimulation. Our studies of PM structure and function in context with
      desensitization of GPCRs action were extended by data indicating participation of
      cholesterol-enriched membrane domains in agonist-specific internalization of
      delta-OR. In HEK293 cells stably expressing delta-OR-G(i)1alpha fusion protein,
      depletion of PM cholesterol was associated with the decrease in affinity of G
      protein response to agonist stimulation, whereas maximum response was unchanged.
      Hydrophobic interior of isolated PM became more "fluid", chaotically organized
      and accessible to water molecules. Validity of this conclusion was supported by
      the analysis of an immediate PM environment of cholesterol molecules in living
      delta-OR-G(i)1alpha-HEK293 cells by fluorescent probes 22- and 25-NBD
      cholesterol. The alteration of plasma membrane structure by cholesterol depletion
      made the membrane more hydrated. Understanding of the positive and negative
      feedback regulatory loops among different OR-initiated signaling cascades (micro
      , delta-, and kappa-OR) is crucial for understanding of the long-term mechanisms
      of drug addiction as the decrease in functional activity of micro-OR may be
      compensated by increase of delta-OR and/or kappa-OR signaling. 

PMID- 24564657
TI  - Outline of therapeutic interventions with muscarinic receptor-mediated
      transmission.
AB  - Muscarinc receptor-mediated signaling takes part in many physiological functions
      ranging from complex higher nervous activity to vegetative responses. Specificity
      of action of the natural muscarinic agonist acetylcholine is effected by action
      on five muscarinic receptor subtypes with particular tissue and cellular
      localization, and coupling preference with different G-proteins and their
      signaling pathways. In addition to physiological roles it is also implicated in
      pathologic events like promotion of carcinoma cells growth, early pathogenesis of
      neurodegenerative diseases in the central nervous system like Alzheimer's disease
      and Parkinson's disease, schizophrenia, intoxications resulting in drug
      addiction, or overactive bladder in the periphery. All of these disturbances
      demonstrate involvement of specific muscarinic receptor subtypes and point to the
      importance to develop selective pharmacotherapeutic interventions. Because of the
      high homology of the orthosteric binding site of muscarinic receptor subtypes
      there is virtually no subtype selective agonist that binds to this site.
      Activation of specific receptor subtypes may be achieved by developing allosteric
      modulators of acetylcholine binding, since ectopic binding domains on the
      receptor are less conserved compared to the orthosteric site. Potentiation of the
      effects of acetylcholine by allosteric modulators would be beneficial in cases
      where acetylcholine release is reduced due to pathological conditions. When
      presynaptic function is severely compromised, the utilization of ectopic agonists
      can be a thinkable solution.

PMID- 24564658
TI  - The interaction of calcium entry and calcium sensitization in the control of
      vascular tone and blood pressure of normotensive and hypertensive rats.
AB  - Increased systemic vascular resistance is responsible for blood pressure (BP)
      elevation in most forms of human or experimental hypertension. The enhanced
      contractility of structurally remodeled resistance arterioles is mediated by
      enhanced calcium entry (through L type voltage-dependent calcium channels - L
      VDCC) and/or augmented calcium sensitization (mediated by RhoA/Rho kinase
      pathway). It is rather difficult to evaluate separately the role of these two
      pathways in BP control because BP response to the blockade of either pathway is
      always dependent on the concomitant activity of the complementary pathway.
      Moreover, vasoconstrictor systems enhance the activity of both pathways, while
      vasodilators attenuate them. The basal fasudil-sensitive calcium sensitization
      determined in rats deprived of endogenous renin-angiotensin system (RAS) and
      sympathetic nervous system (SNS) in which calcium entry was dose-dependently
      increased by L-VDCC opener BAY K8644, is smaller in spontaneously hypertensive
      rats (SHR) than in normotensive Wistar-Kyoto (WKY) rats. In contrast, if
      endogenous RAS and SNS were present in intact rats, fasudil caused a greater BP
      fall in SHR than WKY rats. Our in vivo experiments indicated that the endogenous
      pressor systems (RAS and SNS) augment calcium sensitization mediated by RhoA/Rho
      kinase pathway, whereas the endogenous vasodilator systems (such as nitric oxide)
      attenuate this pathway. However, the modulation of calcium entry and calcium
      sensitization by nitric oxide is strain-dependent because NO deficiency
      significantly augments low calcium entry in WKY and low calcium sensitization in
      SHR. Further in vivo and in vitro experiments should clarify the
      interrelationships between endogenous vasoactive systems and the contribution of
      calcium entry and/or calcium sensitization to BP maintenance in various forms of
      experimental hypertension. 

PMID- 24564659
TI  - Structure, function, and pharmacology of NMDA receptor channels.
AB  - NMDA receptors have received much attention over the last few decades, due to
      their role in many types of neural plasticity on the one hand, and their
      involvement in excitotoxicity on the other hand. There is great interest in
      developing clinically relevant NMDA receptor antagonists that would block
      excitotoxic NMDA receptor activation, without interfering with NMDA receptor
      function needed for normal synaptic transmission and plasticity. This review
      summarizes current understanding of the structure of NMDA receptors and the
      mechanisms of NMDA receptor activation and modulation, with special attention
      given to data describing the properties of various types of NMDA receptor
      inhibition. Our recent analyses point to certain neurosteroids as NMDA receptor
      inhibitors with desirable properties. Specifically, these compounds show use
      dependent but voltage-independent block, that is predicted to preferentially
      target excessive tonic NMDA receptor activation. Importantly, neurosteroids are
      also characterized by use-independent unblock, compatible with minimal disruption
      of normal synaptic transmission. Thus, neurosteroids are a promising class of
      NMDA receptor modulators that may lead to the development of neuroprotective
      drugs with optimal therapeutic profiles. 

PMID- 24564660
TI  - Gain-of-function mutations in the transient receptor potential channels TRPV1 and
      TRPA1: how painful?
AB  - Gain-of-function (GOF) mutations in ion channels are rare events, which lead to
      increased agonist sensitivity or altered gating properties, and may render the
      channel constitutively active. Uncovering and following characterization of such
      mutants contribute substantially to the understanding of the molecular basis of
      ion channel functioning. Here we give an overview of some GOF mutants in
      polymodal ion channels specifically involved in transduction of painful stimuli-
      TRPV1 and TRPA1, which are scrutinized by scientists due to their important role
      in development of some pathological pain states. Remarkably, a substitution of
      single amino acid in the S4-S5 region of TRPA1 (N855S) has been recently
      associated with familial episodic pain syndrome. This mutation increases chemical
      sensitivity of TRPA1, but leaves the voltage sensitivity unchanged. On the other
      hand, mutations in the analogous region of TRPV1 (R557K and G563S) severely
      affect all aspects of channel activation and lead to spontaneous activity.
      Comparison of the effects induced by mutations in homologous positions in
      different TRP receptors (or more generally in other distantly related ion
      channels) may elucidate the gating mechanisms conserved during evolution.

PMID- 24564661
TI  - Allosteric modulation of ligand gated ion channels by ivermectin.
AB  - Ivermectin acts as a positive allosteric regulator of several ligand-gated
      channels including the glutamate-gated chloride channel (GluCl), gamma
      aminobutyric acid type-A receptor, glycine receptor, neuronal alpha7-nicotinic
      receptor and purinergic P2X4 receptor. In most of the ivermectin-sensitive
      channels, the effects of ivermectin include the potentiation of agonist-induced
      currents at low concentrations and channel opening at higher concentrations.
      Based on mutagenesis, electrophysiological recordings and functional analysis of
      chimeras between ivermectin-sensitive and ivermectin-insensitive receptors, it
      has been concluded that ivermectin acts by insertion between transmembrane
      helices. The three-dimensional structure of C. elegans GluCl complexed with
      ivermectin has revealed the details of the ivermectin-binding site, however, no
      generic motif of amino acids could accurately predict ivermectin binding site for
      other ligand gated channels. Here, we will review what is currently known about
      ivermectin binding and modulation of Cys-loop receptor family of ligand-gated ion
      channels and what are the critical structural determinants underlying
      potentiation of the P2X4 receptor channel. 

PMID- 24564662
TI  - Update on the role of spinal cord TRPV1 receptors in pain modulation.
AB  - The structure, expression and function of the transient receptor potential
      vanilloid 1 (TRPV1) receptor were intensively studied since the cloning in 1997
      and TRPV1 receptors are now considered to act as transducers and molecular
      integrators of nociceptive stimuli in the periphery. In contrast, spinal TRPV1
      receptors were studied less extensively and their role in pain modulation is
      still not fully understood. This short review is a follow up on our previous
      summary in this area (Spicarova and Palecek 2008). The aim was to review
      preferentially the most recent findings concerning the role of the spinal TRPV1
      receptors, published within the last five years. The update is given on the
      expression and function of the spinal TRPV1 receptors, their activation by
      endogenous agonists, interaction between the endocannabinoid and endovanillod
      system and possible role of the spinal TRPV1 receptors in pathological pain
      states. There is now mounting evidence that TRPV1 receptors may be an important
      element in modulation of nociceptive information at the spinal cord level and
      represent an interesting target for analgesic therapy. 

PMID- 24564663
TI  - Spatial navigation: implications for animal models, drug development and human
      studies.
AB  - Spatial navigation and memory is considered to be a part of the declarative
      memory system and it is widely used as an animal model of human declarative
      memory. However, spatial tests typically involve only static settings, despite
      the dynamic nature of the real world. Animals, as well as people constantly need
      to interact with moving objects, other subjects or even with entire moving
      environments (flowing water, running stairway). Therefore, we design novel
      spatial tests in dynamic environments to study brain mechanisms of spatial
      processing in more natural settings with an interdisciplinary approach including
      neuropharmacology. We also translate data from neuropharmacological studies and
      animal models into development of novel therapeutic approaches to
      neuropsychiatric disorders and more sensitive screening tests for impairments of
      memory, thought, and behavior. 

PMID- 24564664
TI  - Polysaccharides as cell carriers for tissue engineering: the use of cellulose in
      vascular wall reconstruction.
AB  - Polysaccharides are long carbohydrate molecules of monosaccharide units joined
      together by glycosidic bonds. These biological polymers have emerged as promising
      materials for tissue engineering due to their biocompatibility, mostly good
      availability and tailorable properties. This complex group of biomolecules can be
      classified using several criteria, such as chemical composition (homo- and
      heteropolysaccharides), structure (linear and branched), function in the organism
      (structural, storage and secreted polysaccharides), or source (animals, plants,
      microorganisms). Polysaccharides most widely used in tissue engineering include
      starch, cellulose, chitosan, pectins, alginate, agar, dextran, pullulan, gellan,
      xanthan and glycosaminoglycans. Polysaccharides have been applied for engineering
      and regeneration of practically all tissues, though mostly at the experimental
      level. Polysaccharides have been tested for engineering of blood vessels,
      myocardium, heart valves, bone, articular and tracheal cartilage, intervertebral
      discs, menisci, skin, liver, skeletal muscle, neural tissue, urinary bladder, and
      also for encapsulation and delivery of pancreatic islets and ovarian follicles.
      For these purposes, polysaccharides have been applied in various forms, such as
      injectable hydrogels or porous and fibrous scaffolds, and often in combination
      with other natural or synthetic polymers or inorganic nanoparticles. The immune
      response evoked by polysaccharides is usually mild, and can be reduced by
      purifying the material or by choosing appropriate crosslinking agents. 

PMID- 24564665
TI  - 3D microscopic imaging and evaluation of tubular tissue architecture.
AB  - 3D microscopy and image analysis provide reliable measurements of length,
      branching, density, tortuosity and orientation of tubular structures in
      biological samples. We present a survey of methods for analysis of large samples
      by measurement of local differences in geometrical characteristics. The methods
      are demonstrated on the structure of the capillary bed in a rat brain. 

PMID- 24564666
TI  - Nuclear genetic defects of mitochondrial ATP synthase.
AB  - Disorders of ATP synthase, the key enzyme of mitochondrial energy provision
      belong to the most severe metabolic diseases presenting as early-onset
      mitochondrial encephalo-cardiomyopathies. Up to now, mutations in four nuclear
      genes were associated with isolated deficiency of ATP synthase. Two of them,
      ATP5A1 and ATP5E encode enzyme's structural subunits alpha and epsilon,
      respectively, while the other two ATPAF2 and TMEM70 encode specific ancillary
      factors that facilitate the biogenesis of ATP synthase. All these defects share a
      similar biochemical phenotype with pronounced decrease in the content of fully
      assembled and functional ATP synthase complex. However, substantial differences
      can be found in their frequency, molecular mechanism of pathogenesis, clinical
      manifestation as well as the course of the disease progression. While for TMEM70
      the number of reported patients as well as spectrum of the mutations is steadily
      increasing, mutations in ATP5A1, ATP5E and ATPAF2 genes are very rare.
      Apparently, TMEM70 gene is highly prone to mutagenesis and this type of a rare
      mitochondrial disease has a rather frequent incidence. Here we present overview
      of individual reported cases of nuclear mutations in ATP synthase and discuss,
      how their analysis can improve our understanding of the enzyme biogenesis. 

PMID- 24564668
TI  - Why do we have Purkinje fibers deep in our heart?
AB  - Purkinje fibers were the first discovered component of the cardiac conduction
      system. Originally described in sheep in 1839 as pale subendocardial cells, they
      were found to be present, although with different morphology, in all mammalian
      and avian hearts. Here we review differences in their appearance and extent in
      different species, summarize the current state of knowledge of their function,
      and provide an update on markers for these cells. Special emphasis is given to
      popular model species and human anatomy. 

PMID- 24564667
TI  - Antioxidant and regulatory role of mitochondrial uncoupling protein UCP2 in
      pancreatic beta-cells.
AB  - Research on brown adipose tissue and its hallmark protein, mitochondrial
      uncoupling protein UCP1, has been conducted for half a century and has been
      traditionally studied in the Institute of Physiology (AS CR, Prague), likewise
      UCP2 residing in multiple tissues for the last two decades. Our group has
      significantly contributed to the elucidation of UCP uncoupling mechanism, fully
      dependent on free fatty acids (FFAs) within the inner mitochondrial membrane. Now
      we review UCP2 physiological roles emphasizing its roles in pancreatic beta
      cells, such as antioxidant role, possible tuning of redox homeostasis
      (consequently UCP2 participation in redox regulations), and fine regulation of
      glucose-stimulated insulin secretion (GSIS). For example, NADPH has been firmly
      established as being a modulator of GSIS and since UCP2 may influence redox
      homeostasis, it likely affects NADPH levels. We also point out the role of
      phospholipase iPLA2 isoform gamma in providing FFAs for the UCP2 antioxidant
      function. Such initiation of mild uncoupling hypothetically precedes lipotoxicity
      in pancreatic beta-cells until it reaches the pathological threshold, after which
      the antioxidant role of UCP2 can be no more cell-protective, for example due to
      oxidative stress-accumulated mutations in mtDNA. These mechanisms, together with
      impaired autocrine insulin function belong to important causes of Type 2 diabetes
      etiology. 

PMID- 24564669
TI  - The effect of n-3 fatty acids on glucose homeostasis and insulin sensitivity.
AB  - Type 2 diabetes (T2D) as well as cardiovascular disease (CVD) represent major
      complications of obesity and associated metabolic disorders (metabolic syndrome).
      This review focuses on the effects of long-chain n-3 polyunsaturated fatty acids
      (omega-3) on insulin sensitivity and glucose homeostasis, which are improved by
      omega-3 in many animal models of metabolic syndrome, but remain frequently
      unaffected in humans. Here we focus on: (i) mechanistic aspects of omega-3
      action, reflecting also our experiments in dietary obese mice; and (ii) recent
      studies analysing omega-3's effects in various categories of human subjects. Most
      animal experiments document beneficial effects of omega-3 on insulin sensitivity
      and glucose metabolism even under conditions of established obesity and insulin
      resistance. Besides positive results obtained in both cross-sectional and
      prospective cohort studies on healthy human populations, also some intervention
      studies in prediabetic subjects document amelioration of impaired glucose
      homeostasis by omega-3. However, the use of omega-3 to reduce a risk of new-onset
      diabetes in prediabetic subjects still remains to be further characterized. The
      results of a majority of clinical trials performed in T2D patients suggest that
      omega-3 have none or marginal effects on metabolic control, while effectively
      reducing hypertriglyceridemia in these patients. Despite most of the recent
      randomized clinical trials do not support the role of omega-3 in secondary
      prevention of CVD, this issue remains still controversial. Combined interventions
      using omega-3 and antidiabetic or hypolipidemic drugs should be further explored
      and considered for treatment of patients with T2D and other diseases. 

PMID- 24564670
TI  - Spatially resolved energy transfer in patterned colloidal quantum dot
      heterostructures.
AB  - Spatial uniformity is a key consideration in high-resolution displays and light
      emitting structures fabricated from colloidal quantum dots (QDs). We report
      spatially and spectrally resolved transient photoluminescence measurements of
      laterally patterned QD heterostructures. We show, using a microcontact printing
      technique, that spatially uniform energy transfer can be achieved in a QD donor
      acceptor bilayer system, highlighting the promising potential of colloidal QDs as
      flexible photonic components in next-generation optoelectronic technologies. 

PMID- 24564671
TI  - Assembly of nanoparticles at liquid interfaces: crowding and ordering.
AB  - Experiments with the self-assembly of nanoparticles at liquid interfaces suggest
      that cooperative and slow dynamical processes due to particle crowding at the
      interface govern the adsorption and properties of the final assembly. Here we
      report a numerical approach to studying nonequilibrium adsorption, which
      elucidates these experimental observations. The analysis of particle
      rearrangements shows that local ordering processes are directly related to
      adsorption events at high interface coverage. Interestingly, this feature and the
      mechanism coupling local ordering to adsorption do not seem to change
      qualitatively upon increasing particle size polydispersity, although the latter
      changes the interface microstructure and its final properties. Our results
      indicate how adsorption kinetics can be used for the fabrication of 2D
      nanocomposites with controlled microstructure. 

PMID- 24564674
TI  - Shale gas development: a smart regulation framework.
AB  - Advances in directional drilling and hydraulic fracturing have sparked a natural
      gas boom from shale formations in the United States. Regulators face a rapidly
      changing industry comprised of hundreds of players, operating tens of thousands
      of wells across 30 states. They are often challenged to respond by budget cuts, a
      brain drain to industry, regulations designed for conventional gas developments,
      insufficient information, and deeply polarized debates about hydraulic fracturing
      and its regulation. As a result, shale gas governance remains a halting patchwork
      of rules, undermining opportunities to effectively characterize and mitigate
      development risk. The situation is dynamic, with research and incremental
      regulatory advances underway. Into this mix, we offer the CO/RE framework-
      characterization of risk, optimization of mitigation strategies, regulation, and
      enforcement--to design tailored governance strategies. We then apply CO/RE to
      three types of shale gas risks, to illustrate its potential utility to
      regulators.

PMID- 24564672
TI  - The discovery of asunaprevir (BMS-650032), an orally efficacious NS3 protease
      inhibitor for the treatment of hepatitis C virus infection.
AB  - The discovery of asunaprevir (BMS-650032, 24) is described. This tripeptidic
      acylsulfonamide inhibitor of the NS3/4A enzyme is currently in phase III clinical
      trials for the treatment of hepatitis C virus infection. The discovery of 24 was
      enabled by employing an isolated rabbit heart model to screen for the
      cardiovascular (CV) liabilities (changes to HR and SNRT) that were responsible
      for the discontinuation of an earlier lead from this chemical series, BMS-605339
      (1), from clinical trials. The structure-activity relationships (SARs) developed
      with respect to CV effects established that small structural changes to the P2*
      subsite of the molecule had a significant impact on the CV profile of a given
      compound. The antiviral activity, preclincial PK profile, and toxicology studies
      in rat and dog supported clinical development of BMS-650032 (24). 

PMID- 24564673
TI  - Ser119 phosphorylation modulates the activity and conformation of PRRXL1, a
      homeodomain transcription factor.
AB  - PRRXL1 [paired related homeobox-like 1; also known as DRG11 (dorsal root ganglia
      11)] is a paired-like homeodomain transcription factor expressed in DRG and dSC
      (dorsal spinal cord) nociceptive neurons. PRRXL1 is crucial for the establishment
      and maintenance of nociceptive circuitry, as Prrxl1(-/-) mice present neuronal
      loss, reduced pain sensitivity and failure to thrive. In the present study, we
      show that PRRXL1 is highly phosphorylated in vivo, and that its multiple band
      pattern on electrophoretic analysis is the result of different phosphorylation
      states. PRRXL1 phosphorylation appears to be differentially regulated along the
      dSC and DRG development and it is mapped to two functional domains. One region
      comprises amino acids 107-143, whereas the other one encompasses amino acids 227
      263 and displays repressor activity. Using an immunoprecipitation-MS approach,
      two phosphorylation sites were identified, Ser119 and Ser238. Phosphorylation at
      Ser119 is shown to be determinant for PRRXL1 conformation and transcriptional
      activity. Ser119 phosphorylation is thus proposed as a mechanism for regulating
      PRRXL1 function and conformation during nociceptive system development.

PMID- 24564675
TI  - The team approach to managing dental implant complications: the periodontist's
      point of view.
AB  - Implant-related complications are a fact of life among practitioners who place or
      restore implants. They occur for a variety of reasons with varying consequences.
      Those classified as minor complications are most easily corrected and may have
      little impact on the course of treatment, but severe complications can have
      serious consequence in expense, complexity, and ultimate success. Many severe
      complications may be irreversible, leaving the patient with less desirable
      esthetic options, or worse, permanent disability in terms of speech and function.
      While various members of the dental team may have different points of view,
      implant complications are a concern to all. Successful results require
      comprehensive care, collaborative treatment, and knowledge of dental implant
      complications. Therefore, it is in the best interest of the patient that all
      involved in treatment be aware of the different types of complications that can
      be experienced and learn how to work together as a team to achieve successful
      outcomes. 

PMID- 24564676
TI  - The team approach to managing dental implant complications: strategies for
      treating peri-implantitis.
AB  - Practitioners who are knowledgeable about the risk factors identified by the
      Consensus Report of the Sixth European Workshop on Periodontology and who are
      trained in techniques to eliminate or reduce them may be able to significantly
      improve long-term implant outcomes. A careful review of the literature suggests
      that this will include treatment planning, restoring a patient to periodontal
      heath before initiating care, appropriate implant selection, complete cement
      removal, and diligent recordkeeping that will track changes and enable early
      intervention should complications arise. In the case of the biologic complication
      of peri-implantitis, recent reports suggest that regenerative care may restore
      implants back to health. 

PMID- 24564677
TI  - Implant complications: biomechanical and esthetic considerations--a
      prosthodontist's perspective.
AB  - Implant placement has continued to gain acceptance as a viable solution for the
      treatment of missing teeth, serving as an alternative to dentures or bridges.
      However, clinicians must be aware of and capable of handling complications that
      may accompany the placement of dental implants. Complications can range from
      prosthetic problems stemming from misalignment of implants, to fixed removable
      prosthesis-related complications, to screw-connection impediments. This article
      describes and illustrates how a multidisciplinary team approach can be employed
      to optimize implant treatment planning to successfully overcome these issues. 

PMID- 24564678
TI  - Managing esthetic challenges with anterior implants. Part 1: midfacial recession
      defects from etiology to resolution.
AB  - Dilemmas accompanying esthetic zone implants frequently involve a dehiscence type
      defect of the midfacial tissues. The challenge to the surgical-restorative
      implant team is to understand the etiology associated with such defects and the
      treatment options that can be offered lending to predictable outcomes. Etiologic
      factors are: 1) poor implant spatial positioning; 2) incorrect abutment contour;
      3) excessive implant diameter; 4) horizontal biologic width formation; and 5)
      periodontal phenotype. Remediation treatment can involve: 1) burying the implant
      and allowing the soft tissues to heal naturally over the implant with a surgical
      cover screw known as implant decoronation; 2) augmentation of the soft tissues
      with a connective tissue graft, if needed; 3) stage 2 uncovering of the implant:
      and 4) controlling the abutment-crown contour appropriately with flat or even
      undercontour to maintain the soft tissues in a stable and healthy position long
      term. 

PMID- 24564679
TI  - Peri-implant disease and cemented implant restorations: a multifactorial
      etiology.
AB  - As cemented implant restorations have grown in popularity, so has the incidence
      of peri-implant disease. The association between implant restorations, cement,
      and this disease, however, remains somewhat unclear. This article examines
      factors that may contribute to peri-implant disease, including biology, implant
      depth, restoration depth, and implant material properties, and considers
      potential causes of the disease involving residual cement. Guidance on how to
      prevent this problem from occurring is provided. 

PMID- 24564680
TI  - Accumulation of CTCF-binding sites drives expression divergence between tandemly
      duplicated genes in humans.
AB  - BACKGROUND: During eukaryotic genome evolution, tandem gene duplication is the
      most frequent event giving rise to clustered gene families. However, how
      expression divergence between tandemly duplicated genes has emerged and
      maintained remain unclear. In particular, it is unknown if epigenetic regulators
      have been involved in the process. RESULTS: We demonstrate that CCCTC-binding
      factor (CTCF), the master epigenetic regulator and the only known insulator
      protein in humans, has played a predominant role in generating divergence in both
      expression profiles and expression levels between adjacent paralogs in the human
      genome. This phenomenon was not observed for non-paralogous adjacent genes. After
      tandem duplication events, CTCF-binding sites gradually accumulate between
      paralogs. This trend was more prominent for genes involved in particular
      functions. CONCLUSIONS: The accumulation of CTCF-binding sites drives expression
      divergence of tandemly duplicated genes. This process is likely targeted by
      natural selection. Our study reveals the importance of CTCF to the evolution of
      animal diversity and complexity.

PMID- 24564681
TI  - Efficacy of prenatal ultrasonography in diagnosing urogenital developmental
      anomalies in newborns.
AB  - BACKGROUND: Showing a prevalence rate of 0.5-0.8%, urogenital malformations
      discovered in newborns is regarded relatively common. The aim of this study is to
      examine the efficacy of ultrasound diagnostics in detecting developmental
      disorders in the urogenital system. METHODS: We have processed the prenatal
      sonographic and postnatal clinical details of 175 urogenital abnormalities in 140
      newborns delivered with urogenital malformation according to EUROCAT
      recommendations over a 5-year period between 2006 and 2010. The patients were
      divided into three groups; Group 1: prenatal sonography and postnatal
      examinations yielded fully identical results. Group 2: postnatally detected
      urogenital changes were partially discovered in prenatal investigations. Group 3:
      prenatal sonography failed to detect the urogenital malformation identified in
      postnatal examinations. Urogenital changes representing part of certain multiple
      disorders associated with chromosomal aberration were investigated separately.
      RESULTS: Prenatal sonographic diagnosis and postnatal results completely
      coincided in 45%, i.e. 63/140 of cases in newborns delivered with urogenital
      developmental disorders. In 34/140 cases (24%), discovery was partial, while in
      43/140 patients (31%), no urogenital malformation was detected prenatally. No
      associated malformations were observed in 108 cases, in 57 of which (53%), the
      results of prenatal ultrasonography and postnatal examinations showed complete
      coincidence. Prenatally, urogenital changes were found in 11 patients (10%),
      whereas no urogenital disorders were diagnosed in 40 cases (37%) by
      investigations prior to birth. Urogenital disorders were found to represent part
      of multiple malformations in a total of 28 cases as follows: prenatal diagnosis
      of urogenital malformation and the findings of postnatal examinations completely
      coincided in three patients (11%), partial coincidence was found in 22 newborns
      (79%) and in another three patients (11%), the disorder was not detected
      prenatally. In four newborns, chromosomal aberration was associated with the
      urogenital disorder; 45,X karyotype was detected in two patients, trisomy 9 and
      trisomy 18 were found in one case each. CONCLUSION: In approximately half of the
      cases, postnatally diagnosed abnormalities coincided with the prenatally
      discovered fetal urogenital developmental disorders. The results have confirmed
      that ultrasonography plays an important role in diagnosing urogenital
      malformations but it fails to detect all of the urogenital developmental
      abnormalities.

PMID- 24564682
TI  - Simultaneous inferences based on empirical Bayes methods and false discovery
      rates ineQTL data analysis.
AB  - BACKGROUND: Genome-wide association studies (GWAS) have identified hundreds of
      genetic variants associated with complex human diseases, clinical conditions and
      traits. Genetic mapping of expression quantitative trait loci (eQTLs) is
      providing us with novel functional effects of thousands of single nucleotide
      polymorphisms (SNPs). In a classical quantitative trail loci (QTL) mapping
      problem multiple tests are done to assess whether one trait is associated with a
      number of loci. In contrast to QTL studies, thousands of traits are measured
      alongwith thousands of gene expressions in an eQTL study. For such a study, a
      huge number of tests have to be performed (~10(6)). This extreme multiplicity
      gives rise to many computational and statistical problems. In this paper we have
      tried to address these issues using two closely related inferential approaches:
      an empirical Bayes method that bears the Bayesian flavor without having much a
      priori knowledge and the frequentist method of false discovery rates. A three
      component t-mixture model has been used for the parametric empirical Bayes (PEB)
      method. Inferences have been obtained using Expectation/Conditional Maximization
      Either (ECME) algorithm. A simulation study has also been performed and has been
      compared with a nonparametric empirical Bayes (NPEB) alternative. RESULTS: The
      results show that PEB has an edge over NPEB. The proposed methodology has been
      applied to human liver cohort (LHC) data. Our method enables to discover more
      significant SNPs with FDR<10% compared to the previous study done by Yang et al.
      (Genome Research, 2010). CONCLUSIONS: In contrast to previously available methods
      based on p-values, the empirical Bayes method uses local false discovery rate
      (lfdr) as the threshold. This method controls false positive rate.

PMID- 24564683
TI  - Novel amplex red oxidases based on noncanonical DNA structures: property studies
      and applications in microRNA detection.
AB  - G-triplex has recently been identified as a new secondary structure in G-rich
      sequences. However, its functions and biological roles remain largely unknown.
      This study first developed two kinds of Amplex Red oxidases, which were based on
      relatively new G-triplex structure and a common G-quadruplex one. A collection of
      DNA binding assays including circular dichroism (CD) spectroscopy, a CD melting
      assay, and a UV titration study were used to determine the G-triplex structure of
      G3 oligomer. The low intrinsic oxidative activity of hemin was significantly
      enhanced using G-triplex or G-quadruplex. Only one key guanine deletion from the
      G3 oligomer or G4 one could result in a much decreased Amplex Red oxidation
      activity. To the best of our knowledge, this is the first case reporting direct
      use of air as the oxidant for fluorescence generation based on DNAzyme
      strategies. Further mechanism studies demonstrated an involvement of on-site H2O2
      generation from O2 and water and a following oxidation of Amplex Red to
      resorufin, causing a fluorescence enhancement. Furthermore, the newly developed
      oxidases have been effectively used in microRNA detection, using only one biotin
      labeled probe and one small-molecule substrate. The conjugation of a target DNA
      to the G-triplex- or G-quadruplex-forming sequence enabled one to produce G
      triplex or G-quadruplex by endonuclease in the presence of a slight amount of
      miRNA and amplify the signal of fluorescence from the oxidation of Amplex Red.
      Our findings of novel Amplex Red oxidases could potentially be used in a wide
      range of applications. 

PMID- 24564684
TI  - Genome-wide structural modelling of TCR-pMHC interactions.
AB  - BACKGROUND: The adaptive immune response is antigen-specific and triggered by
      pathogen recognition through T cells. Although the interactions and mechanisms of
      TCR-peptide-MHC (TCR-pMHC) have been studied over three decades, the biological
      basis for these processes remains controversial. As an increasing number of high
      throughput binding epitopes and available TCR-pMHC complex structures, a fast
      genome-wide structural modelling of TCR-pMHC interactions is an emergent task for
      understanding immune interactions and developing peptide vaccines. RESULTS: We
      first constructed the PPI matrices and iMatrix, using 621 non-redundant PPI
      interfaces and 398 non-redundant antigen-antibody interfaces, respectively, for
      modelling the MHC-peptide and TCR-peptide interfaces, respectively. The iMatrix
      consists of four knowledge-based scoring matrices to evaluate the hydrogen bonds
      and van der Waals forces between sidechains or backbones, respectively. The
      predicted energies of iMatrix are high correlated (Pearson's correlation
      coefficient is 0.6) to 70 experimental free energies on antigen-antibody
      interfaces. To further investigate iMatrix and PPI matrices, we inferred the
      701,897 potential peptide antigens with significant statistic from 389 pathogen
      genomes and modelled the TCR-pMHC interactions using available TCR-pMHC complex
      structures. These identified peptide antigens keep hydrogen-bond energies and
      consensus interactions and our TCR-pMHC models can provide detailed interacting
      models and crucial binding regions. CONCLUSIONS: Experimental results demonstrate
      that our method can achieve high precision for predicting binding affinity and
      potential peptide antigens. We believe that iMatrix and our template-based method
      can be useful for the binding mechanisms of TCR-pMHC complexes and peptide
      vaccine designs.

PMID- 24564686
TI  - Variations in the prevalence of metabolic syndrome in adolescents according to
      different criteria used for diagnosis: which definition should be chosen for this
      age group?
AB  - BACKGROUND: Despite the increasing prevalence of metabolic syndrome in
      adolescents, there is no consensus for its diagnosis. METHODS: A cross-sectional
      study was conducted to compare the prevalence of metabolic syndrome in
      adolescents by different definitions, evaluate their concordance, and suggest
      which definition to apply in this population. A total of 851 adolescents between
      10 and 18 years of age were evaluated. Anthropometric (weight, height, waist
      circumference), biochemical (glucose, lipid profile), and blood pressure data
      were taken. The prevalence of metabolic syndrome was determined by the
      definitions of the International Diabetes Federation (IDF) and four published
      studies by Cook et al., de Ferranti et al., Agudelo et al., and Ford et al.
      Concordance was determined according to the kappa index. RESULTS: The prevalence
      of metabolic syndrome was 0.9%, 3.8%, 4.1%, 10.5%, and 11.4%, according to the
      IDF, Cook et al., Ford et al., Agudelo et al., and de Ferranti et al.
      definitions, respectively. The most prevalent components were
      hypertriglyceridemia and low high-density lipoprotein cholesterol, whereas the
      least prevalent components were abdominal obesity and hyperglycemia. The highest
      concordance was found between the definitions by Cook et al. and Ford et al.
      (kappa=0.92), whereas the greatest discordance was between the de Ferranti et al.
      and IDF definitions (kappa=0.14). CONCLUSIONS: Metabolic syndrome and its
      components were conditions present in the adolescents of this study. In this
      population, with a high prevalence of dyslipidemia and a lower prevalence of
      abdominal obesity and hyperglycemia, the recommendation to diagnose metabolic
      syndrome would be that used by Ford et al.

PMID- 24564685
TI  - Dietary management of childhood diarrhea in low- and middle-income countries: a
      systematic review.
AB  - BACKGROUND: Current WHO guidelines on the management and treatment of diarrhea in
      children strongly recommend continued feeding alongside the administration of
      oral rehydration solution and zinc therapy, but there remains some debate
      regarding the optimal diet or dietary ingredients for feeding children with
      diarrhea. METHODS: We conducted a systematic search for all published randomized
      controlled trials evaluating food-based interventions among children under five
      years old with diarrhea in low- and middle-income countries. We classified 29
      eligible studies into one or more comparisons: reduced versus regular lactose
      liquid feeds, lactose-free versus lactose-containing liquid feeds, lactose-free
      liquid feeds versus lactose-containing mixed diets, and commercial/specialized
      ingredients versus home-available ingredients. We used all available outcome data
      to conduct random-effects meta-analyses to estimate the average effect of each
      intervention on diarrhea duration, stool output, weight gain and treatment
      failure risk for studies on acute and persistent diarrhea separately. RESULTS:
      Evidence of low-to-moderate quality suggests that among children with acute
      diarrhea, diluting or fermenting lactose-containing liquid feeds does not affect
      any outcome when compared with an ordinary lactose-containing liquid feeds. In
      contrast, moderate quality evidence suggests that lactose-free liquid feeds
      reduce duration and the risk of treatment failure compared to lactose-containing
      liquid feeds in acute diarrhea. Only limited evidence of low quality was
      available to assess either of these two approaches in persistent diarrhea, or to
      assess lactose-free liquid feeds compared to lactose-containing mixed diets in
      either acute or persistent diarrhea. For commercially prepared or specialized
      ingredients compared to home-available ingredients, we found low-to-moderate
      quality evidence of no effect on any outcome in either acute or persistent
      diarrhea, though when we restricted these analyses to studies where both
      intervention and control diets were lactose-free, weight gain in children with
      acute diarrhea was shown to be greater among those fed with a home-available
      diet. CONCLUSIONS: Among children in low- and middle-income countries, where the
      dual burden of diarrhea and malnutrition is greatest and where access to
      proprietary formulas and specialized ingredients is limited, the use of locally
      available age-appropriate foods should be promoted for the majority of acute
      diarrhea cases. Lactose intolerance is an important complication in some cases,
      but even among those children for whom lactose avoidance may be necessary,
      nutritionally complete diets comprised of locally available ingredients can be
      used at least as effectively as commercial preparations or specialized
      ingredients. These same conclusions may also apply to the dietary management of
      children with persistent diarrhea, but the evidence remains limited.

PMID- 24564687
TI  - Late toxicity following craniospinal radiation for early-stage medulloblastoma.
AB  - BACKGROUND: The purpose of this study is to review late toxicity following
      craniospinal radiation for early-stage medulloblastoma. MATERIAL AND METHODS:
      Between 1963 and 2008, 53 children with stage M0 (n = 50) or M1 (n = 3)
      medulloblastoma were treated at our institution. The median age at diagnosis was
      7.1 years (range 1.2-18.5). The median craniospinal irradiation (CSI) dose was
      28.8 Gy (range 21.8-38.4). The median total dose, including boost, was 54 Gy
      (range 42.4-64.8 Gy). Since 1963, the CSI dose has been incrementally lowered and
      the high-risk boost volume reduced. Twenty-one patients (40%) received
      chemotherapy in their initial management, including 12 who received concurrent
      chemotherapy. Late sequelae were evaluated by analyzing medical records and
      conducting phone interviews with surviving patients and/or care-takers.
      Complications were graded using the NCI Common Terminology Criteria for Adverse
      Events, version 4.0. RESULTS: The median follow-up for all patients was 15.4
      years (range 0.4-44.4) and for living patients it was 24 years (range 5.6-44.4).
      The overall survival, cause-specific survival, and progression-free survival
      rates at 10 years were 67%, 67%, and 71%, respectively. Sixteen patients (41% of
      patients who survived five years or more) developed grade 3 + toxicity; 15 of
      these 16 patients received a CSI dose > 23.4 Gy. The most common grade 3 +
      toxicities for long-term survivors are hearing impairment requiring intervention
      (20.5%) and cognitive impairment (18%) prohibiting independent living. Four
      patients developed secondary (non-skin) malignancies, including three
      meningiomas, one rhabdomyosarcoma, and one glioblastoma multiforme. Three
      patients (5.6%) died from treatment complications, including radionecrosis,
      severe cerebral edema, and fatal secondary malignancy. CONCLUSION: Ongoing
      institutional and cooperative group efforts to minimize radiation exposure are
      justified given the high rate of serious toxicity observed in our long-term
      survivors. Follow-up through long-term multidisciplinary clinics is important and
      warranted for all patients exposed to radiotherapy in childhood.

PMID- 24564689
TI  - Forward. The art of hearing conservation.

PMID- 24564688
TI  - Auditory risk estimates for youth target shooting.
AB  - OBJECTIVE: To characterize the impulse noise exposure and auditory risk for youth
      recreational firearm users engaged in outdoor target shooting events. The youth
      shooting positions are typically standing or sitting at a table, which places the
      firearm closer to the ground or reflective surface when compared to adult
      shooters. DESIGN: Acoustic characteristics were examined and the auditory risk
      estimates were evaluated using contemporary damage-risk criteria for unprotected
      adult listeners and the 120-dB peak limit suggested by the World Health
      Organization (1999) for children. STUDY SAMPLE: Impulses were generated by 26
      firearm/ammunition configurations representing rifles, shotguns, and pistols used
      by youth. Measurements were obtained relative to a youth shooter's left ear.
      RESULTS: All firearms generated peak levels that exceeded the 120 dB peak limit
      suggested by the WHO for children. In general, shooting from the seated position
      over a tabletop increases the peak levels, LAeq8 and reduces the unprotected
      maximum permissible exposures (MPEs) for both rifles and pistols. Pistols pose
      the greatest auditory risk when fired over a tabletop. CONCLUSION: Youth should
      utilize smaller caliber weapons, preferably from the standing position, and
      always wear hearing protection whenever engaging in shooting activities to reduce
      the risk for auditory damage.

PMID- 24564690
TI  - Shooting habits of youth recreational firearm users.
AB  - OBJECTIVE: This study surveyed youth recreational firearm users (YRFUs) regarding
      shooting habits, reported use of hearing protection devices (HPDs), self-assessed
      auditory status, and attitudes about firearm noise and hearing loss. DESIGN: A
      descriptive study using a 28-item survey administered by personal interview.
      STUDY SAMPLE: Two-hundred and ten youth aged 10 to 17 years responded. RESULTS:
      Seventy-eight percent of those surveyed began shooting before the age of ten. The
      majority reported using large caliber firearms capable of rapid fire for both
      hunting and target practice. Most youths in this study were not aware of, and
      therefore, were not utilizing HPDs specifically designed for the shooting sports.
      Ten percent of subjects reported constant tinnitus and 45% notice tinnitus
      occurred or worsened after shooting. Although the majority of YRFUs reported good
      or perfect hearing, a small percentage (4-5%) of youth reported having only
      'fair" hearing. CONCLUSION: YRFUs are putting themselves at risk beginning at a
      young age for noise-induced hearing loss (NIHL) and tinnitus based on self
      reported shooting habits and inconsistent use of HPDs during both target practice
      and hunting activities. This research highlights the need for early education and
      intervention efforts to minimize the risk of NIHL in youth.

PMID- 24564691
TI  - Effectiveness of the Brazilian version of the Dangerous Decibels((r)) educational
      program.
AB  - OBJECTIVE: To evaluate the effectiveness of a Brazilian version of the Dangerous
      Decibels((r)) educational program in increasing students' knowledge and
      positively changing their attitudes and intended behaviors related to NIHL
      prevention and to decrease exposures to loud sounds and the barriers related to
      hearing protective strategies (HPS). DESIGN: This is a prospective longitudinal
      controlled study. STUDY SAMPLE: Third to fifth graders (n = 220) filled out a
      baseline questionnaire; participated in a 60 minutes Dangerous Decibels((r))
      classroom presentation; answered a follow-up questionnaire immediately after the
      presentation; worked with their teachers on an activity booklet about hearing
      health ten weeks later; and filled out a three-months follow-up questionnaire.
      Students that did not receive health hearing education served as a control group
      (n = 51). A mixed analysis of variance was performed, with time as the within
      subjects independent variable, and the intervention as the between-subjects
      independent variable. RESULTS: The study group exhibited significant short- and
      long-term improvements in knowledge, attitudes, and intended behavior related to
      NIHL and acoustic trauma prevention, and in decreased exposures to loud sounds
      and barriers to the use of hearing protective strategies. CONCLUSIONS: This study
      demonstrated the effectiveness of a Brazilian version of the Dangerous Decibels
      classroom program with an additional supplementary workbook intervention.

PMID- 24564692
TI  - Warfighter auditory situation awareness: effects of augmented hearing
      protection/enhancement devices and TCAPS for military ground combat applications.
AB  - OBJECTIVE: To determine the effects of current hearing protection/enhancement
      devices (HPEDs) and tactical communications and protection systems (TCAPS) on
      auditory detection and identification of three critical military signals
      associated with potential "threats." DESIGN: Utilizing a 6 * 3 within-subject
      experimental design, 24 normal-hearing Virginia Tech Reserve Officer Training
      Corps (ROTC) cadets and active duty soldiers participated. STUDY SAMPLE: Five
      HPEDS and TCAP devices plus the open ear were tested. On each trial, either
      wearing a device or with open ears, subjects walked along a 3000-foot line of
      discrete distance markers toward the auditory threat, which was not visible but
      still within line-of-sight over flat terrain, stopping to listen when instructed.
      On approach to the threat, the linear distance at first detection was measured,
      followed by a continued approach until positive identification occurred. Then the
      subject reversed direction, retreating away from the threat until detection was
      lost. RESULTS: ANOVA and post hoc tests were applied to determine statistically
      significant differences among HPEDs, TCAPS, and the open ear on the objective
      detection and identification distance measures. CONCLUSIONS: The results have
      serious implications for selection of HPDs, HPEDs, and TCAPS for applications
      where preservation of auditory situational awareness via the fundamental
      detection and identification tasks are essential.

PMID- 24564693
TI  - Short-term variability of pure-tone thresholds obtained with TDH-39P earphones.
AB  - OBJECTIVE: To estimate the short-term variability and correlates of variability
      in pure-tone thresholds obtained using audiometric equipment designed for
      occupational use, and to examine the justification for excluding 8 kHz as a
      mandatory threshold in occupational hearing conservation programs. METHOD: Pure
      tone thresholds and other hearing-related tests (e.g. noise dosimetry, otoscopy,
      middle-ear assessment) were conducted with a group of 527 adults between 20 and
      69 years of age. Five measurement visits were completed by participants within 14
      days. RESULTS: The 50% critical difference boundaries were - 5 and 0 dB at 4 kHz
      and below and - 5 and 5 dB at 6 and 8 kHz. The likelihood of spurious notches due
      to test-retest variability was substantially lower than the likelihood of failing
      to detect a notched configuration when present. Correlates of variability
      included stimulus frequency, baseline threshold, acoustic reflectance of the ear,
      average noise exposure during the previous eight hours, age, and the tester's
      level of education in audiology. CONCLUSION: The short-term variability in 8-kHz
      pure-tone thresholds obtained with the TDH-39P earphone was slightly greater than
      at other frequencies, but this difference was not large enough to justify the
      disadvantages stemming from the inability to detect a 6-kHz notch.

PMID- 24564695
TI  - Noise and age-related hearing loss: a study of 40 123 gold miners in South
      Africa.
AB  - OBJECTIVE AND DESIGN: This retrospective cohort study aimed to describe the
      differential effect of noise exposure and age-related hearing loss in a large
      sample of gold miners in South Africa. STUDY SAMPLE: Audiological data of 40 123
      South African mine workers were investigated. Data of a non-noise-exposed control
      group (n = 6162) and group exposed to underground noise (>= 85 dB A (TWA) (n = 33
      961) were included. Within these two larger noise-exposed groups two homogenous
      exposure groups (HEG) were also selected for analyses, namely the driller group
      (n = 4399) and the administration group (administrative workers) (n = 2211).
      Participants were categorized in terms of noise exposure, age, and race. RESULTS:
      Significantly different thresholds (worse for underground noise group) with
      respect to the median for all frequencies after adjusting for age was evident
      between the noise-exposed and control groups (ANCOVA). The largest differences in
      hearing thresholds between the noise-exposed and control groups were observed at
      3 and 4 kHz in the age group 36 to 45 years. Administration and driller group
      differed significantly (driller group worse results) with respect to the mean
      LFA512 and HFA346 after adjusting for age (ANCOVA). Black males had significantly
      better high-frequency hearing compared with white male counterparts but
      significantly worse low-frequency hearing. CONCLUSION: Age was the most important
      influence on hearing thresholds for the noise and control groups. Race was shown
      to be a very significant factor determining susceptibility to NIHL and ARHL.

PMID- 24564694
TI  - Temporary threshold shift after impulse-noise during video game play: laboratory
      data.
AB  - OBJECTIVE: Prevention of temporary threshold shift (TTS) after laboratory-based
      exposure to pure-tones, broadband noise, and narrowband noise signals has been
      achieved, but prevention of TTS under these experimental conditions may not
      accurately reflect protection against hearing loss following impulse noise. This
      study used a controlled laboratory-based TTS paradigm that incorporated impulsive
      stimuli into the exposure protocol; development of this model could provide a
      novel platform for assessing proposed therapeutics. DESIGN: Participants played a
      video game that delivered gunfire-like sound through headphones as part of a
      target practice game. Effects were measured using audiometric threshold
      evaluations and distortion product otoacoustic emissions (DPOAEs). The sound
      level and number of impulses presented were sequentially increased throughout the
      study. STUDY SAMPLE: Participants were normal-hearing students at the University
      of Florida who provided written informed consent prior to participation. RESULTS:
      TTS was not reliably induced by any of the exposure conditions assessed here.
      However, there was significant individual variability, and a subset of subjects
      showed TTS under some exposure conditions. CONCLUSIONS: A subset of participants
      demonstrated reliable threshold shifts under some conditions. Additional
      experiments are needed to better understand and optimize stimulus parameters that
      influence TTS after simulated impulse noise.

PMID- 24564696
TI  - Methods for evaluating temporal trends in noise exposure.
AB  - OBJECTIVE: Hearing conservation programs have been mandatory in many US
      industries since 1983. Since then, three program elements (audiometric testing,
      hearing protection, and training) have been the focus of much research. By
      comparison, little has been done on noise exposure evaluation. DESIGN: Temporal
      trends in time weighted average (TWA) exposures and the fraction of measurements
      exceeding 85 dBA were evaluated by facility, by exposure group within facility,
      and by individual worker within facility. STUDY SAMPLE: A large dataset (> 10 000
      measurements over 20 years) from eight facilities operated by a multinational
      aluminum manufacturing company was studied. RESULTS: Overall, exposures declined
      across locations over the study period. Several facilities demonstrated
      substantial reductions in exposure, and the results of mean noise levels and
      exceedance fractions generally showed good agreement. The results of analyses at
      the individual level diverged with analyses by facility and exposure group within
      facility, suggesting that individual-level analyses, while challenging, may
      provide important information not available from coarser levels of analysis.
      CONCLUSIONS: Validated metrics are needed to allow for assessment of temporal
      trends in noise exposure. Such metrics will improve our ability to characterize,
      in a standardized manner, efforts to reduce noise-induced hearing loss.

PMID- 24564697
TI  - Interventions to prevent occupational noise-induced hearing loss: a Cochrane
      systematic review.
AB  - OBJECTIVE: To assess the effectiveness of interventions for preventing
      occupational noise exposure or hearing loss compared to no intervention or
      alternative interventions. DESIGN: We searched biomedical databases up to 25
      January 2012 for randomized controlled trials (RCT), controlled before-after
      studies and interrupted time-series of hearing loss prevention among workers
      exposed to noise. STUDY SAMPLE: We included 19 studies with 82 794 participants
      evaluating effects of hearing loss prevention programs (HLPP). The overall
      quality of studies was low to very low, as rated using the GRADE approach.
      RESULTS: One study of stricter legislation showed a favorable effect on noise
      levels. Three studies, of which two RCTs, did not find an effect of a HLPP. Four
      studies showed that better use of hearing protection devices in HLPPs decreased
      the risk of hearing loss. In four other studies, workers in a HLPP still had a
      0.5 dB greater hearing loss at 4 kHz (95% CI - 0.5 to 1.7) than non-exposed
      workers. In two similar studies there was a substantial risk of hearing loss in
      spite of a HLPP. CONCLUSIONS: Stricter enforcement of legislation and better
      implementation of HLPPs can reduce noise levels in workplaces. Better evaluations
      of technical interventions and long-term effects are needed.

PMID- 24564698
TI  - Neuropsychological and physiological correlates of fatigue following traumatic
      brain injury.
AB  - BACKGROUND: Fatigue is a common and debilitating phenomenon experienced by
      individuals with traumatic brain injury (TBI) that can negatively influence rate
      and extent of functional recovery by reducing participation in brain injury
      rehabilitation services and increasing maladaptive lifestyle practices. The
      underlying mechanisms of TBI-related fatigue are not entirely understood and
      focused research on symptom reduction or prevention is limited. REVIEW: The
      current review of the literature suggests that the aetiology of TBI-related
      fatigue can be viewed as a multifactorial and complex model impacting
      physiological systems (i.e. endocrine, skeletal muscle and cardiorespiratory)
      that can be directly or indirectly influenced by neuropsychological correlates
      including cognitive and psychological impairment. Distinguishing central from
      peripheral fatigue is helpful in this regard. Potential therapeutic strategies
      and pharmacological agents to help alleviate fatigue in this patient population
      are discussed.

PMID- 24564701
TI  - Validity of a Non-Speech Dynamic Assessment of Phonemic Awareness via the
      Alphabetic Principle.
AB  - Most assessments of phonemic awareness require speech responses and cannot be
      used with individuals with severe speech impairments who may use augmentative and
      alternative communication (AAC). This study investigated the reliability and
      construct validity of the Dynamic Assessment of Phonemic Awareness via the
      Alphabetic Principle (DAPA-AP), which does not require speech. In all, 17 adults
      with mild to moderate intellectual disabilities completed the DAPA-AP, a letter
      sound knowledge task, four measures of phonological awareness, and two reading
      assessments. Results indicated the DAPA-AP was both a reliable and valid
      assessment of phonemic awareness for this sample. Consequently, the DAPA-AP
      represents an important step in developing phonemic awareness assessments that
      have the potential to be suitable for use with a wide range of individuals,
      including those with SSI.

PMID- 24564700
TI  - In vitro characterization of bacterial and chloroplast Hsp70 systems reveals an
      evolutionary optimization of the co-chaperones for their Hsp70 partner.
AB  - The chloroplast Hsp70 (heat-shock protein of 70 kDa) system involved in protein
      folding in Chlamydomonas reinhardtii consists of HSP70B, the DnaJ homologue CDJ1
      and the GrpE-type nucleotide-exchange factor CGE1. The finding that HSP70B needs
      to be co-expressed with HEP2 (Hsp70 escort protein 2) to become functional
      allowed the reconstitution of the chloroplast Hsp70 system in vitro and
      comparison with the homologous Escherichia coli system. Both systems support
      luciferase refolding and display ATPase and holdase activities. Steady-state
      activities are low and strongly stimulated by the co-chaperones, whose
      concentrations need to be balanced to optimally support luciferase refolding.
      Although the co-chaperones of either system generally stimulate ATPase and
      folding-assistance activities of the other, luciferase refolding is reduced ~10
      fold and <2-fold if either Hsp70 is supplemented with the foreign DnaJ and GrpE
      protein respectively, suggesting an evolutionary specialization of the co
      chaperones for their Hsp70 partner. Distinct features are that HSP70B's steady
      state ATPase exhibits ~20-fold higher values for Vmax and Km and that the HSP70B
      system displays a ~6-fold higher folding assistance on denatured luciferase.
      Although truncating up to 16 N-terminal amino acids of CGE1 does not affect
      HSP70B's general ATPase and folding-assistance activities in the physiological
      temperature range, further deletions hampering dimerization of CGE1 via its N
      terminal coiled coil do. 

PMID- 24564702
TI  - N-terminal protein tails act as aggregation protective entropic bristles: the
      SUMO case.
AB  - The formation of beta-sheet enriched amyloid fibrils constitutes the hallmark of
      many diseases but is also an intrinsic property of polypeptide chains in general,
      because the formation of compact globular proteins comes at the expense of an
      inherent sequential aggregation propensity. In this context, identification of
      strategies that enable proteins to remain functional and soluble in the cell has
      become a central issue in chemical biology. We show here, using human SUMO
      proteins as a model system, that the recurrent presence of disordered tails
      flanking globular domains might constitute yet another of these protective
      strategies. These short, disordered, and highly soluble protein segments would
      act as intramolecular entropic bristles, reducing the overall protein intrinsic
      aggregation propensity and favoring thus the attainment and maintenance of
      functional conformations. 

PMID- 24564703
TI  - Palladium-silver-activated ZnO surface: highly selective methane sensor at
      reasonably low operating temperature.
AB  - Metal oxide semiconductors (MOS) are well known as reducing gas sensors. However,
      their selectivity and operating temperature have major limitations. Most of them
      show cross sensitivity and the operating temperatures are also relatively higher
      than the value reported here. To resolve these problems, here, we report the use
      of palladium-silver (70-30%) activated ZnO thin films as a highly selective
      methane sensor at low operating temperature (~100  degrees C). Porous ZnO thin
      films were deposited on fluorine-doped tin oxide (FTO)-coated glass substrates by
      galvanic technique. X-ray diffraction showed polycrystalline nature of the films,
      whereas the morphological analyses (field emission scanning electron microscopy)
      showed flake like growth of the grains mainly on xy plane with high surface
      roughness (107 nm). Pd-Ag (70-30%) alloy was deposited on such ZnO films by e
      beam evaporation technique with three different patterns, namely, random dots,
      ultrathin (~1 nm) layer and thin (~5 nm) layer as the activation layer. ZnO films
      with Pd-Ag dotted pattern were found show high selectivity towards methane (with
      respect to H2S and CO) and sensitivity (~80%) at a comparatively low operating
      temperature of about 100 degrees C. This type of sensor was found to have higher
      methane selectivity in comparison to other commercially available reducing gas
      sensor. 

PMID- 24564699
TI  - Cellular phenotype and extracellular vesicles: basic and clinical considerations.
AB  - Early work on platelet and erythrocyte vesicles interpreted the phenomena as a
      discard of material from cells. Subsequently, vesicles were studied as possible
      vaccines and, most recently, there has been a focus on the effects of vesicles on
      cell fate. Recent studies have indicated that extracellular vesicles, previously
      referred to as microvesicles or exosomes, have the capacity to change the
      phenotype of neighboring cells. Extensive work has shown that vesicles derived
      from either the lung or liver can enter bone marrow cells (this is a
      prerequisite) and alter their fate toward that of the originating liver and lung
      tissue. Lung vesicles interacted with bone marrow cells result in the bone marrow
      cells expressing surfactants A-D, Clara cell protein, and aquaporin-5 mRNA. In a
      similar vein, liver-derived vesicles induce albumin mRNA in target marrow cells.
      The vesicles contain protein, mRNA, microRNA, and noncoding RNA and variably some
      DNA. This genetic package is delivered to cells and alters the phenotype. Further
      studies have shown that initially the altered phenotype is due to the transfer of
      mRNA and a transcriptional modulator, but long-term epigenetic changes are
      induced through transfer of a transcriptional factor, and the mRNA is rapidly
      degraded in the cell. Studies on the capacity of vesicles to restore injured
      tissue have been quite informative. Mesenchymal stem cell-derived vesicles are
      able to reverse the injury to the damaged liver and kidney. Other studies have
      shown that mesenchymal stem cell-derived vesicles can reverse radiation toxicity
      of bone marrow stem cells. Extracellular vesicles offer an intriguing strategy
      for treating a number of diseases characterized by tissue injury. 

PMID- 24564704
TI  - Random forests on Hadoop for genome-wide association studies of multivariate
      neuroimaging phenotypes.
AB  - MOTIVATION: Multivariate quantitative traits arise naturally in recent
      neuroimaging genetics studies, in which both structural and functional
      variability of the human brain is measured non-invasively through techniques such
      as magnetic resonance imaging (MRI). There is growing interest in detecting
      genetic variants associated with such multivariate traits, especially in genome
      wide studies. Random forests (RFs) classifiers, which are ensembles of decision
      trees, are amongst the best performing machine learning algorithms and have been
      successfully employed for the prioritisation of genetic variants in case-control
      studies. RFs can also be applied to produce gene rankings in association studies
      with multivariate quantitative traits, and to estimate genetic similarities
      measures that are predictive of the trait. However, in studies involving hundreds
      of thousands of SNPs and high-dimensional traits, a very large ensemble of trees
      must be inferred from the data in order to obtain reliable rankings, which makes
      the application of these algorithms computationally prohibitive. RESULTS: We have
      developed a parallel version of the RF algorithm for regression and genetic
      similarity learning tasks in large-scale population genetic association studies
      involving multivariate traits, called PaRFR (Parallel Random Forest Regression).
      Our implementation takes advantage of the MapReduce programming model and is
      deployed on Hadoop, an open-source software framework that supports data
      intensive distributed applications. Notable speed-ups are obtained by introducing
      a distance-based criterion for node splitting in the tree estimation process.
      PaRFR has been applied to a genome-wide association study on Alzheimer's disease
      (AD) in which the quantitative trait consists of a high-dimensional neuroimaging
      phenotype describing longitudinal changes in the human brain structure. PaRFR
      provides a ranking of SNPs associated to this trait, and produces pair-wise
      measures of genetic proximity that can be directly compared to pair-wise measures
      of phenotypic proximity. Several known AD-related variants have been identified,
      including APOE4 and TOMM40. We also present experimental evidence supporting the
      hypothesis of a linear relationship between the number of top-ranked mutated
      states, or frequent mutation patterns, and an indicator of disease severity.
      AVAILABILITY: The Java codes are freely available at
      http://www2.imperial.ac.uk/~gmontana.

PMID- 24564705
TI  - Electroactive layer-by-layer plasmonic architectures based on Au nanorods.
AB  - Nanostructured films based on Au nanorods (NRs) have been obtained by layer-by
      layer (LbL) assembly driven by electrostatic interaction between metal
      nanoparticles and polyelectrolytes. Multilayer films have been fabricated by
      using LbL assembly of poly(sodium styrenesulfonate) (PSS) and positively charged
      Au NRs on a polyelectrolyte-modified substrate. The effect of fabrication
      parameters, including the nature of the substrate, the polyelectrolyte initial
      anchoring layer, and the number of layers has been investigated by means of UV
      vis absorbance spectroscopy and atomic force microscopy (AFM). The results
      demonstrated the dependence of morphology and plasmonic features in the
      multilayered nanostructured architectures from the nature of the anchoring
      polyelectrolyte on the substrate, the number of layers, and the kind of NR mutual
      assembly. In addition, a study of the electrochemical activity at the
      solid/liquid interface has been carried out in order to assess charge transport
      through the NR multilayer by using two molecular probes in solution, namely,
      potassium ferricyanide, a common and well-established redox mediator with
      reversible behavior, and cytochrome C, a robust model redox protein. The
      presented systematic study of the immobilization of Au NRs opens the venue to
      several application areas, such as (bio)chemical sensing. 

PMID- 24564707
TI  - Modeling the mechanism of coagulum formation in dispersions.
AB  - The stability of colloidal dispersions is of crucial importance because the
      properties of dispersions are strongly affected by the degree of coagulation.
      Whereas the coagulation kinetics for quiescent (i.e., nonstirred) and diluted
      systems is well-established, the behavior of concentrated dispersions subjected
      to shear is still not fully understood. We employ the discrete element method
      (DEM) for the simulation of coagulation of concentrated colloidal dispersions.
      Normal forces between interacting particles are described by a combination of the
      Derjaguin, Landau, Verwey, and Overbeek (DLVO) and Johnson, Kendall, and Roberts
      (JKR) theories. We show that, in accordance with the expectations, the
      coagulation behavior depends strongly on the particle volume fraction, the
      surface potential, and the shear rate. Moreover, we demonstrate that the doublet
      formation rate is insufficient for the description of the coagulation kinetics
      and that the detailed DEM model is able to explain the autocatalytic nature of
      the coagulation of stabilized dispersions subjected to shear. With no adjustable
      parameters we are able to provide semiquantitative predictions of the coagulation
      behavior in the high-shear regions for a broad range of particle volume
      fractions. The results obtained using the DEM model can provide valuable
      guidelines for the operation of industrial dispersion processes. 

PMID- 24564706
TI  - Finishing bacterial genome assemblies with Mix.
AB  - MOTIVATION: Among challenges that hamper reaping the benefits of genome assembly
      are both unfinished assemblies and the ensuing experimental costs. First,
      numerous software solutions for genome de novo assembly are available, each
      having its advantages and drawbacks, without clear guidelines as to how to choose
      among them. Second, these solutions produce draft assemblies that often require a
      resource intensive finishing phase. METHODS: In this paper we address these two
      aspects by developing Mix , a tool that mixes two or more draft assemblies,
      without relying on a reference genome and having the goal to reduce contig
      fragmentation and thus speed-up genome finishing. The proposed algorithm builds
      an extension graph where vertices represent extremities of contigs and edges
      represent existing alignments between these extremities. These alignment edges
      are used for contig extension. The resulting output assembly corresponds to a set
      of paths in the extension graph that maximizes the cumulative contig length.
      RESULTS: We evaluate the performance of Mix on bacterial NGS data from the GAGE-B
      study and apply it to newly sequenced Mycoplasma genomes. Resulting final
      assemblies demonstrate a significant improvement in the overall assembly quality.
      In particular, Mix is consistent by providing better overall quality results even
      when the choice is guided solely by standard assembly statistics, as is the case
      for de novo projects. AVAILABILITY: Mix is implemented in Python and is available
      at https://github.com/cbib/MIX, novel data for our Mycoplasma study is available
      at http://services.cbib.u-bordeaux2.fr/mix/.

PMID- 24564708
TI  - Informed public choices for low-carbon electricity portfolios using a computer
      decision tool.
AB  - Reducing CO2 emissions from the electricity sector will likely require policies
      that encourage the widespread deployment of a diverse mix of low-carbon
      electricity generation technologies. Public discourse informs such policies. To
      make informed decisions and to productively engage in public discourse, citizens
      need to understand the trade-offs between electricity technologies proposed for
      widespread deployment. Building on previous paper-and-pencil studies, we
      developed a computer tool that aimed to help nonexperts make informed decisions
      about the challenges faced in achieving a low-carbon energy future. We report on
      an initial usability study of this interactive computer tool. After providing
      participants with comparative and balanced information about 10 electricity
      technologies, we asked them to design a low-carbon electricity portfolio.
      Participants used the interactive computer tool, which constrained portfolio
      designs to be realistic and yield low CO2 emissions. As they changed their
      portfolios, the tool updated information about projected CO2 emissions,
      electricity costs, and specific environmental impacts. As in the previous paper
      and-pencil studies, most participants designed diverse portfolios that included
      energy efficiency, nuclear, coal with carbon capture and sequestration, natural
      gas, and wind. Our results suggest that participants understood the tool and used
      it consistently. The tool may be downloaded from http://cedmcenter.org/tools-for
      cedm/informing-the-public-about-low-carbon-technologies/ . 

PMID- 24564709
TI  - Special issue in honor of Professor Otto Sticher.

PMID- 24564710
TI  - Towards integrative gene functional similarity measurement.
AB  - BACKGROUND: In Gene Ontology, the "Molecular Function" (MF) categorization is a
      widely used knowledge framework for gene function comparison and prediction. Its
      structure and annotation provide a convenient way to compare gene functional
      similarities at the molecular level. The existing gene similarity measures,
      however, solely rely on one or few aspects of MF without utilizing all the rich
      information available including structure, annotation, common terms, lowest
      common parents. RESULTS: We introduce a rank-based gene semantic similarity
      measure called InteGO by synergistically integrating the state-of-the-art gene-to
      gene similarity measures. By integrating three GO based seed measures, InteGO
      significantly improves the performance by about two-fold in all the three species
      studied (yeast, Arabidopsis and human). CONCLUSIONS: InteGO is a systematic and
      novel method to study gene functional associations. The software and description
      are available at http://www.msu.edu/~jinchen/InteGO.

PMID- 24564711
TI  - The proteomics of prostate cancer exosomes.
AB  - Exosomes and other microvesicles are emerging as rich reservoirs of tumor
      specific proteins and biomarkers for cancer detection and progression. For
      prostate cancer, exosomes secreted by the prostate can be isolated from prostatic
      secretions, seminal fluid, tissue, urine or blood for further proteomic analysis.
      Structurally, prostate-derived exosomes are distinct in size, membrane
      composition and specific prostate protein content, potentially providing a novel
      and easily isolatable source of biomarkers from clinical biofluids. The key to
      these isolation strategies will be the targeting of specific prostatic proteins
      expressed in these exosomes, thus requiring detailed proteomic characterizations.
      A summary of ongoing efforts to characterize the proteome of these unique
      prostate cancer-associated exosomes and their potential applications for use in
      biomarker assays is presented. 

PMID- 24564712
TI  - Single nanowire light-emitting diodes using uniaxial and coaxial InGaN/GaN
      multiple quantum wells synthesized by metalorganic chemical vapor deposition.
AB  - We report the controlled synthesis of InGaN/GaN multiple quantum well (MQW)
      uniaxial (c-plane) and coaxial (m-plane) nanowire (NW) heterostructures by
      metalorganic chemical vapor deposition. Two kinds of heterostructure NW light
      emitting diodes (LEDs) have been fabricated: (1) 10 pairs of InGaN/GaN MQW layers
      in the c-plane on the top of n-GaN NWs where Mg-doped p-GaN NW is axially grown
      (2) p-GaN/10 pairs of InGaN/GaN shell structure were surrounded by n-GaN core.
      Here, we discuss a comparative analysis based on the m-plane and the c-plane
      oriented InGaN/GaN MQW NW arrays. High-resolution transmission electron
      microscopy studies revealed that the barrier and the well structures of MQW were
      observed to be substantially clear with regular intervals while the interface
      regions were extremely sharp. The c-plane and m-plane oriented MQW single NW was
      utilized for the parallel assembly fabrication of the LEDs via a focused ion
      beam. The polarization induced effects on the c-plane and m-plane oriented MQW
      NWs were precisely compared via power dependence electroluminescence. The
      electrical properties of m-plane NWs exhibited superior characteristics than that
      of c-plane NWs owing to the absence of piezoelectric polarization fields.
      According to this study, high-quality m-plane coaxial NWs can be utilized for the
      realization of high-brightness LEDs. 

PMID- 24564713
TI  - Exploring the association between short/long preceding birth intervals and child
      mortality: using reference birth interval children of the same mother as
      comparison.
AB  - BACKGROUND: This study used data from recent Demographic and Health Surveys (DHS)
      to examine the impact of short or long preceding birth intervals on neonatal and
      under-five mortality. In order to minimize the effect of selection issues, we
      examined child mortality outcomes of the same mother, comparing short or long
      interval births against births with what had previously been considered optimal
      intervals. METHODS: We analyzed 47 DHS datasets from low- and middle-income
      countries. For each dataset, we compared neonatal and under-five mortality of
      short preceding interval births (<18 months, <24 months) to reference interval
      births (24-<60 months) of a mother, using conditional logistic regression
      matching on the mother. We also conducted the same matched analysis for long (>=
      60 months, >= 72 months) preceding interval births. These associations were then
      meta-analyzed. We also stratified the analyses by mothers' completed fertility
      (fertility at end of reproductive period) to assess whether maternal
      characteristics highly correlated with completed fertility modify the association
      between birth interval and child mortality. RESULTS: Children with shorter
      preceding intervals had increased odds of both neonatal (<24 months, OR: 1.61,
      95% CI: 1.52-1.70) and under-five mortality (<24 months, OR: 1.48, 95% CI: 1.40
      1.56). When the associations were stratified by the mothers' completed fertility,
      the impact of short intervals was greatly reduced or eliminated for low fertility
      mothers. In contrast, mortality associations became stronger for children of high
      fertility mothers. However, when the births of high fertility mothers were
      limited to birth orders 2-4, the associations were comparable to those of low
      fertility mothers. Longer preceding birth intervals had lower odds of mortality
      than reference intervals (i.e. under-5 mortality for >= 60 months, OR 0.59, 95%
      CI: 0.52-0.67). This effect was also mediated by mothers' completed fertility;
      there was a strong protective effect of longer birth intervals for the high
      fertility mothers but not for low fertility mothers. CONCLUSIONS: These analyses
      reproduced findings reported in previous literature that shorter birth intervals
      are associated with higher child mortality. However the negative impact of short
      birth intervals may only occur in high parity births. Reproductive health
      interventions that seek to lengthen birth intervals may have larger impact by
      targeting women with high parity. This finding is consistent with the concept of
      maternal depletion as the underlying cause of increased adverse child outcomes
      associated with shorter birth intervals.

PMID- 24564715
TI  - Three-dimensional carbon interdigitated electrode arrays for redox-amplification.
AB  - Three-dimensional (3D) carbon interdigitated electrode arrays (IDEAs) were
      fabricated using inexpensive, conventional, UV photolithography of SU-8 with
      modified exposure and post exposure bake settings followed by pyrolysis in an
      inert environment. The sensor performance was investigated as a function of both
      the IDEA digit width/gap ratio and digit height under flow and no flow
      conditions. We demonstrated a gradual increase in redox amplification with an
      increase in the IDEA digit width/gap ratio. The highest amplification of 37 was
      obtained for a width/gap ratio of 1.58 and for an electrode height of 1.1 MUm.
      Redox amplification also increases significantly with an increase in the IDEA
      height, from a factor of 9 at a 0.22 MUm digit height to a factor of 37 at a 1.1
      MUm height. The effect of potential sweep rates on redox amplification was also
      investigated. As the sweep rate was decreased from 50 mV/s to 5 mV/s, the
      collection efficiency increased from 0.92 to 0.97, whereas the amplification
      increased from 7 to 25. Under flow conditions, the amplification decreases
      substantially as the cycling of the redox species is impeded by convection,
      resulting in a drop in collection efficiency. The highest amplification of 37
      dropped to 4 for the same electrode at a flow rate of 500 nL/s. Under flow, redox
      amplification increased with an increase in the IDEA height. 

PMID- 24564714
TI  - A tool for mapping Single Nucleotide Polymorphisms using Graphics Processing
      Units.
AB  - BACKGROUND: Single Nucleotide Polymorphism (SNP) genotyping analysis is very
      susceptible to SNPs chromosomal position errors. As it is known, SNPs mapping
      data are provided along the SNP arrays without any necessary information to
      assess in advance their accuracy. Moreover, these mapping data are related to a
      given build of a genome and need to be updated when a new build is available. As
      a consequence, researchers often plan to remap SNPs with the aim to obtain more
      up-to-date SNPs chromosomal positions. In this work, we present G-SNPM a GPU
      (Graphics Processing Unit) based tool to map SNPs on a genome. METHODS: G-SNPM is
      a tool that maps a short sequence representative of a SNP against a reference DNA
      sequence in order to find the physical position of the SNP in that sequence. In G
      SNPM each SNP is mapped on its related chromosome by means of an automatic three
      stage pipeline. In the first stage, G-SNPM uses the GPU-based short-read mapping
      tool SOAP3-dp to parallel align on a reference chromosome its related sequences
      representative of a SNP. In the second stage G-SNPM uses another short-read
      mapping tool to remap the sequences unaligned or ambiguously aligned by SOAP3-dp
      (in this stage SHRiMP2 is used, which exploits specialized vector computing
      hardware to speed-up the dynamic programming algorithm of Smith-Waterman). In the
      last stage, G-SNPM analyzes the alignments obtained by SOAP3-dp and SHRiMP2 to
      identify the absolute position of each SNP. RESULTS AND CONCLUSIONS: To assess G
      SNPM, we used it to remap the SNPs of some commercial chips. Experimental results
      shown that G-SNPM has been able to remap without ambiguity almost all SNPs. Based
      on modern GPUs, G-SNPM provides fast mappings without worsening the accuracy of
      the results. G-SNPM can be used to deal with specialized Genome Wide Association
      Studies (GWAS), as well as in annotation tasks that require to update the SNP
      mapping probes.

PMID- 24564716
TI  - Progressive Cone Dysfunction and Geographic Atrophy of the Macula in Late Stage
      Autosomal Dominant Vitreoretinochoroidopathy (ADVIRC).
AB  - Autosomal dominant vitreoretinochoroidopathy (ADVIRC) is a rare inherited ocular
      disease associated with distinct mutations in the BEST1 gene. Typically, patients
      have only mild visual impairment, and rarely do patients have moderate or severe
      visual impairment, often as a result of vitreous hemorrhage. We now describe
      progressive central macular atrophy and cone dysfunction leading to visual loss
      in an elderly ADVIRC patient 33 years after initial presentation. 

PMID- 24564717
TI  - Enhancing enzyme stability by construction of polymer-enzyme conjugate micelles
      for decontamination of organophosphate agents.
AB  - Enhancing the stability of enzymes under different working environments is
      essential if the potential of enzyme-based applications is to be realized for
      nanomedicine, sensing and molecular diagnostics, and chemical and biological
      decontamination. In this study, we focus on the enzyme, organophosphorus
      hydrolase (OPH), which has shown great promise for the nontoxic and noncorrosive
      decontamination of organophosphate agents (OPs) as well as for therapeutics as a
      catalytic bioscavanger against nerve gas poisoning. We describe a facile approach
      to stabilize OPH using covalent conjugation with the amphiphilic block copolymer,
      Pluronic F127, leading to the formation of F127-OPH conjugate micelles, with the
      OPH on the micelle corona. SDS-PAGE and MALDI-TOF confirmed the successful
      conjugation, and transmission electron microscopy (TEM) and dynamic light
      scattering (DLS) revealed ~100 nm size micelles. The conjugates showed
      significantly enhanced stability and higher activity compared to the unconjugated
      OPH when tested (i) in aqueous solutions at room temperature, (ii) in aqueous
      solutions at higher temperatures, (iii) after multiple freeze/thaw treatments,
      (iv) after lyophilization, and (v) in the presence of organic solvents. The F127
      OPH conjugates also decontaminated paraoxon (introduced as a chemical agent
      simulant) on a polystyrene film surface and on a CARC (Chemical Agent Resistant
      Coating) test panel more rapidly and to a larger extent compared to free OPH. We
      speculate that, in the F127-OPH conjugates (both in the micellar form as well as
      in the unaggregated conjugate), the polypropylene oxide block of the copolymer
      interacts with the surface of the OPH and this confinement of the OPH reduces the
      potential for enzyme denaturation and provides robustness to OPH at different
      working environments. The use of such polymer-enzyme conjugate micelles with
      improved enzyme stability opens up new opportunities for numerous civilian and
      Warfighter applications. 

PMID- 24564718
TI  - Spectral probabilities of top-down tandem mass spectra.
AB  - BACKGROUND: In mass spectrometry-based proteomics, the statistical significance
      of a peptide-spectrum or protein-spectrum match is an important indicator of the
      correctness of the peptide or protein identification. In bottom-up mass
      spectrometry, probabilistic models, such as the generating function method, have
      been successfully applied to compute the statistical significance of peptide
      spectrum matches for short peptides containing no post-translational
      modifications. As top-down mass spectrometry, which often identifies intact
      proteins with post-translational modifications, becomes available in many
      laboratories, the estimation of statistical significance of top-down protein
      identification results has come into great demand. RESULTS: In this paper, we
      study an extended generating function method for accurately computing the
      statistical significance of protein-spectrum matches with post-translational
      modifications. Experiments show that the extended generating function method
      achieves high accuracy in computing spectral probabilities and false discovery
      rates. CONCLUSIONS: The extended generating function method is a non-trivial
      extension of the generating function method for bottom-up mass spectrometry. It
      can be used to choose the correct protein-spectrum match from several candidate
      protein-spectrum matches for a spectrum, as well as separate correct protein
      spectrum matches from incorrect ones identified from a large number of tandem
      mass spectra.

PMID- 24564719
TI  - Structural analysis of the novel influenza A (H7N9) viral Neuraminidase
      interactions with current approved neuraminidase inhibitors Oseltamivir,
      Zanamivir, and Peramivir in the presence of mutation R289K.
AB  - BACKGROUND: Since late March 2013, there has been another global health concern
      with a sudden wave of flu infections by a novel strain of avian influenza A
      (H7N9) virus in China. To-date, there have been more than 100 infections with 23
      deaths. It is more worrying as this viral strain has never been detected in
      humans and only been found to be of low-pathogenicity. Currently, there are 3
      effective neuraminidase inhibitors for this H7N9 virus strain, i.e. oseltamivir,
      zanamivir, and peramivir. These drugs have been used for treatment of the H7N9
      influenza in China. However, how these inhibitors work and affect the binding
      cavity of the novel H7N9 neuraminidase in the presence of potential mutations has
      not been disclosed. In our study, we investigate steric effects and subsequently
      show the conformational restraints of the inhibitor-binding site of the non
      mutated and mutated H7N9 neuraminidase structures to different drug compounds.
      RESULTS: Combination of molecular docking and Molecular Dynamics simulation
      reveal that zanamivir forms more favorable and stable complex than oseltamivir
      and peramivir when binding to the active site of the H7N9 neuraminidase. And it
      is likely that the novel influenza A (H7N9) virus adopts a higher probability to
      acquire resistance to peramivir than the other two inhibitors. Conformational
      changes induced by the mutation R289K causes loss of number of hydrogen bonds
      between the inhibitors and the H7N9 viral neuraminidase in 2 out of 3 complexes.
      In addition, our results of binding-affinity relationships of the 3 inhibitors
      with the viral neuraminidase proteins of previous pandemics (H1N1, H5N1) and the
      current novel H7N9 reflected the extent of binding effectiveness of the 3
      inhibitors to the novel H7N9 neuraminidase. CONCLUSIONS: The results are novel
      and specific for the A/Hangzhou/1/2013(H7N9) influenza strain. Furthermore, the
      protocol could be useful for further drug-binding analysis and prediction of
      future viral mutations to which the virus evolves through adaptation and acquires
      resistance to the current available drugs.

PMID- 24564721
TI  - Linking high parity and maternal and child mortality: what is the impact of lower
      health services coverage among higher order births?
AB  - BACKGROUND: A number of data sets show that high parity births are associated
      with higher child mortality than low parity births. The reasons for this
      relationship are not clear. In this paper we investigate whether high parity is
      associated with lower coverage of key health interventions that might lead to
      increased mortality. METHODS: We used DHS data from 10 high fertility countries
      to examine the relationship between parity and coverage for 8 child health
      intervention and 9 maternal health interventions. We also used the LiST model to
      estimate the effect on maternal and child mortality of the lower coverage
      associated with high parity births. RESULTS: Our results show a significant
      relationship between coverage of maternal and child health services and birth
      order, even when controlling for poverty. The association between coverage and
      parity for maternal health interventions was more consistently significant across
      countries all countries, while for child health interventions there were fewer
      overall significant relationships and more variation both between and within
      countries. The differences in coverage between children of parity 3 and those of
      parity 6 are large enough to account for a 12% difference in the under-five
      mortality rate and a 22% difference in maternal mortality ratio in the countries
      studied. CONCLUSIONS: This study shows that coverage of key health interventions
      is lower for high parity children and the pattern is consistent across countries.
      This could be a partial explanation for the higher mortality rates associated
      with high parity. Actions to address this gap could help reduce the higher
      mortality experienced by high parity birth.

PMID- 24564722
TI  - Solo surgery--early results of robot-assisted three-dimensional laparoscopic
      hysterectomy.
AB  - OBJECTIVE: Report of our initial experience in laparoscopic hysterectomy by a
      solo surgeon using a robotic camera system with three-dimensional visualisation.
      MATERIAL AND METHODS: This novel device (Einstein Vision(r), B. Braun, Aesculap
      AG, Tuttlingen, Germany) (EV) was used for laparoscopic supracervical
      hysterectomy (LASH) performed by one surgeon. Demographic data, clinical and
      surgical parameters were evaluated. Our first 22 cases, performed between June
      and November 2012, were compared with a cohort of 22 age-matched controls who
      underwent two-dimensional LASH performed by the same surgeon with a second
      surgeon assisting. RESULTS: Compared to standard two-dimensional laparoscopic
      hysterectomy, there were no significant differences regarding duration of
      surgery, hospital stay, blood loss or incidence of complications. The number of
      trocars used was significantly higher in the control group (p <.0001). All
      hysterectomies in the treatment group were performed without assistance of a
      second physician. CONCLUSION: Robot-assisted solo surgery laparoscopic
      hysterectomy is a feasible and safe procedure. Duration of surgery, hospital
      stay, blood loss, and complication rates are comparable to a conventional
      laparoscopic hysterectomy.

PMID- 24564723
TI  - Binocular training reduces amblyopic visual acuity impairment.
AB  - Amblyopia is the most common cause of monocular visual impairment. Patching,
      which is modestly effective, is the current treatment of amblyopia in children.
      There is no clinically approved treatment for adults. The present study is a
      clinical trial (non-sham controlled and non-randomized) that assessed the
      efficacy of binocular training for improvement of the visual acuity in children
      and adults with amblyopia. Twenty-two amblyopic subjects ranging in age from 5 to
      73 (mean: 36.2) years for whom patching and/or surgical treatments did not
      correct their visual impairment completed an average of 14.5 sessions of
      binocular training over a period of 4 to 6 weeks. Random dot kinematograms were
      presented dichoptically to the two eyes and the participants' task was to
      identify the direction of motion of the targets. Mean visual acuity improvement
      was 0.34 LogMAR (range: 0.1-0.58 LogMAR) and was shown to persist 6 months
      following the cessation of binocular training. Our study provides results in a
      large number of patients that confirm the clinical effectiveness of binocular
      training as a treatment for amblyopia in improving visual acuity in both children
      and adults. Moreover, this study is the first to demonstrate that the
      improvements in visual function were maintained for 6 months in the absence of
      any additional treatment.

PMID- 24564724
TI  - The results of Brown syndrome surgery with superior oblique split tendon
      lengthening.
AB  - PURPOSE: To report the surgical outcome of superior oblique tendon split
      lengthening for management of patients with severe type of congenital Brown
      syndrome. Brown syndrome is characterized by hypotropia in primary position and
      limitation of elevation in adduction more than -4. MATERIALS AND METHODS:
      Fourteen consecutive patients with severe congenital Brown syndrome underwent
      superior oblique split lengthening surgery (10 mm). The amount of hypotropia in
      primary gaze and the degree of elevation in adduction were compared before and
      after the surgery. Any surgical complications were also recorded. RESULTS:
      Surgery was performed on 15 eyes in 11 female and 3 male subjects. Mean
      postoperative follow-up time was 12.93 +/- 1.79 months (ranging from 10 to 16
      months). Average hypotropia in primary gaze improved from 16.2 +/- 5.5 prism
      diopters (range: 10-25 prism diopters) preoperatively to 5.9 +/- 4.0 prism
      diopters (range: 0-18 prism diopters) postoperatively recorded at final follow-up
      examination (p < 0.001). The limitation in adduction improved from -7.2 +/- 4.5
      (range: -6 to -8) preoperatively to -1.8 +/- 1.3 (range: zero to -5)
      postoperatively (p < 0.001). No surgical complications were noted. CONCLUSION:
      Superior oblique split lengthening has a significant effect on reducing primary
      gaze hypotropia and improving elevation in adduction. This technique should be
      considered for the treatment of patients with severe congenital Brown syndrome.

PMID- 24564725
TI  - The accuracy of the plusoptiX for measuring pupillary distance.
AB  - INTRODUCTION: The plusoptiX photoscreener provides a number of measurements,
      including an estimate of inter-pupillary distance. We compare the plusoptiX
      photoscreening measurements of pupillary distance to that of an experienced
      optician in order to measure the accuracy of this reading. METHODS: A
      retrospective chart review was done on 731 patients ranging in age from 1 to 16
      years. Of these, 256 patients had both a plusoptiX photoscreening and a pupillary
      distance measurement by one of our office opticians. RESULTS: Of the 236 patients
      evaluated, 142 were orthophoric, 97 were esotropic, and 17 were exotropic. The
      mean absolute difference for the entire group between the two measurements was
      0.3 mm. For the orthophoric patients, this metric was 0.3 mm, while for the
      esotropic patients it was 0.8 mm. There were too few exotropic patients to obtain
      reliable statistics. CONCLUSIONS: Although the average difference between the
      optician's measurements and those provided by the plusoptiX was within 0.5 mm for
      orthophoric patients, the variability of the measurements provided by the
      plusoptiX was too great to permit us to recommend the device as an alternative to
      the optician for routinely dispensing spectacles.

PMID- 24564726
TI  - Standardising reported outcomes of surgery for intermittent exotropia--a
      systematic literature review.
AB  - BACKGROUND: Intermittent exotropia (IXT) is one of the most common strabismus
      entities worldwide, but it remains poorly understood. Investigators differ
      regarding which parameters should be used to characterize IXT and to evaluate
      interventions. Surgery is an established treatment option but problems can arise
      when comparing surgical effectiveness if there is a wide range of different
      outcome measures that can be used. This study aimed to assess the extent of
      standardization of reported outcomes in studies of surgery for IXT. METHODS: With
      institutional R&D committee approval, we conducted, according to a predefined
      protocol, a systematic literature review of outcomes of surgery for IXT published
      in the last 10 years. The databases used were Medline and EMBASE. Two analysts
      independently performed the searches. The separate lists were then compared and
      collated to maximize our return rate for included papers and allow evaluation of
      our strategies. RESULTS: Fifty-six studies met our inclusion criteria. Thirty-two
      were retrospective and twenty-four prospective. Outcome measures varied widely
      between studies and variously included ocular alignment, stereopsis, visual
      acuity, re-operation rate, and postoperative drift. Even for ocular alignment,
      there was no agreed definition of postoperative success. Time frames for
      assessing outcomes ranged from two months to two years after surgery.
      CONCLUSIONS: The lack of harmony in outcome reporting for studies of surgery for
      IXT is counterproductive. We suggest 4 core outcomes for all future studies,
      which have already been incorporated into two current randomized trials:
      alignment, near stereoacuity, control score, and quality of life score.

PMID- 24564727
TI  - The physiologist Ewald Hering (1834-1918): Curriculum vitae.

PMID- 24564729
TI  - An unusual case of gingival enlargement: peripheral odontogenic fibroma.
AB  - The peripheral odontogenic fibroma (POdF) is an uncommon gingival enlargement. It
      is a benign, unencapsulated exophytic gingival mass, which is composed of fibrous
      connective tissue associated with various amounts of calcifications and islands
      of odontogenic epithelium.The lesion is usually firm to palpation and non-tender,
      and it could be mistaken for other more common exophytic gingival lesions, such
      as peripheral ossifying fibroma, pyogenic granuloma, or peripheral giant cell
      granuloma. Therefore, a histopathologic examination is necessary for accurate
      diagnosis. This article presents a well-documented case of POdF and a review of
      the literature in regards to its diagnostic features, treatment modalities, and
      recurrence. 

PMID- 24564728
TI  - Breastfeeding for reducing the risk of pneumonia morbidity and mortality in
      children under two: a systematic literature review and meta-analysis.
AB  - BACKGROUND: Suboptimal breastfeeding practices among infants and young children
      <24 months of age are associated with elevated risk of pneumonia morbidity and
      mortality. We conducted a systematic review and meta-analysis to quantify the
      protective effects of breastfeeding exposure against pneumonia incidence,
      prevalence, hospitalizations and mortality. METHODS: We conducted a systematic
      literature review of studies assessing the risk of selected pneumonia morbidity
      and mortality outcomes by varying levels of breastfeeding exposure among infants
      and young children <24 months of age. We used random effects meta-analyses to
      generate pooled effect estimates by outcome, age and exposure level. RESULTS:
      Suboptimal breastfeeding elevated the risk of pneumonia morbidity and mortality
      outcomes across age groups. In particular, pneumonia mortality was higher among
      not breastfed compared to exclusively breastfed infants 0-5 months of age (RR:
      14.97; 95% CI: 0.67-332.74) and among not breastfed compared to breastfed infants
      and young children 6-23 months of age (RR: 1.92; 95% CI: 0.79-4.68). CONCLUSIONS:
      Our results highlight the importance of breastfeeding during the first 23 months
      of life as a key intervention for reducing pneumonia morbidity and mortality.

PMID- 24564730
TI  - Maxillofacial prosthetics: history to modern applications. Part 2--Speech and
      swallow prostheses.
AB  - Speech and swallow difficulties can arise from a variety of causes. Regardless of
      etiology, many of the problems can be solved by the fabrication of a speech or
      swallow prosthesis. Considering the relatively large patient population affected
      by these disorders, there is limited awareness of maxillofacial prosthetic
      solutions among the general dental and medical communities. A brief history of
      speech and swallow prostheses is presented along with recommendations for
      diagnosis and referral. 

PMID- 24564731
TI  - Reconstructing the modular recombination history of Staphylococcus aureus phages.
AB  - BACKGROUND: Viruses that infect bacteria, called phages, are well-known for their
      extreme mosaicism, in which an individual genome shares many different parts with
      many others. The mechanisms for creating these mosaics are largely unknown but
      are believed to be recombinations, either illegitimate, or partly homologous. In
      order to reconstruct the history of these recombinations, we need to identify the
      positions where recombinations may have occurred, and develop algorithms to
      generate and explore the possible reconstructions. RESULTS: We first show that,
      provided that their gene order is co-linear, genomes of phages can be aligned,
      even if large parts of their sequences lack any detectable similarity and are
      annotated hypothetical proteins. We give such an alignment for 31 Staphylococcus
      aureus phage genomes, and algorithms that can be used in any similar context.
      These alignments provide the datasets needed for a combinatorial study of
      recombinations. We next reconstruct the most likely recombination history of the
      set of 31 phages, under the hypothesis that recombinations are partly homologous.
      This history relies on the computational identification of missing phages.
      CONCLUSIONS: This first combinatorial study of modular recombinations acts as a
      proof of concept. We show that alignments of whole genomes are feasible for large
      sets of phages, and that this representation yields data that can be used to
      reconstruct parts of the evolutionary history of these organisms.

PMID- 24564732
TI  - The Risa R/Bioconductor package: integrative data analysis from experimental
      metadata and back again.
AB  - BACKGROUND: The ISA-Tab format and software suite have been developed to break
      the silo effect induced by technology-specific formats for a variety of data
      types and to better support experimental metadata tracking. Experimentalists
      seldom use a single technique to monitor biological signals. Providing a multi
      purpose, pragmatic and accessible format that abstracts away common constructs
      for describing Investigations, Studies and Assays, ISA is increasingly popular.
      To attract further interest towards the format and extend support to ensure
      reproducible research and reusable data, we present the Risa package, which
      delivers a central component to support the ISA format by enabling effortless
      integration with R, the popular, open source data crunching environment. RESULTS:
      The Risa package bridges the gap between the metadata collection and curation in
      an ISA-compliant way and the data analysis using the widely used statistical
      computing environment R. The package offers functionality for: i) parsing ISA-Tab
      datasets into R objects, ii) augmenting annotation with extra metadata not
      explicitly stated in the ISA syntax; iii) interfacing with domain specific R
      packages iv) suggesting potentially useful R packages available in Bioconductor
      for subsequent processing of the experimental data described in the ISA format;
      and finally v) saving back to ISA-Tab files augmented with analysis specific
      metadata from R. We demonstrate these features by presenting use cases for mass
      spectrometry data and DNA microarray data. CONCLUSIONS: The Risa package is open
      source (with LGPL license) and freely available through Bioconductor. By making
      Risa available, we aim to facilitate the task of processing experimental data,
      encouraging a uniform representation of experimental information and results
      while delivering tools for ensuring traceability and provenance tracking.
      SOFTWARE AVAILABILITY: The Risa package is available since Bioconductor 2.11
      (version 1.0.0) and version 1.2.1 appeared in Bioconductor 2.12, both along with
      documentation and examples. The latest version of the code is at the development
      branch in Bioconductor and can also be accessed from GitHub
      https://github.com/ISA-tools/Risa, where the issue tracker allows users to report
      bugs or feature requests.

PMID- 24564734
TI  - Edge oxidation effect of chemical-vapor-deposition-grown graphene
      nanoconstriction.
AB  - The edge oxidation effects of chemical-vapor-deposition-grown graphene devices
      with nanoconstrictions of different sizes are presented. The effects of edge
      oxidation on the doping level of a nanoconstriction graphene device were
      identified by Raman spectroscopy and using the back-gate-voltage-dependent
      resistance. Strong p-type doping was observed as the size of nanoconstriction
      decreased. The Dirac point of the graphene device shifted toward positive
      voltage, and the positions of the G and 2D peaks in Raman spectroscopy shifted
      toward a higher wave number, indicating the p-type doping effect of the graphene
      device. p-type doping was lifted by deep-ultraviolet light illumination under a
      nitrogen atmosphere at room temperature. p-type doping was restored by deep
      ultraviolet light illumination under an oxygen atmosphere at room temperature.
      Edge oxidation in the narrow structures explains the origin of the p-type doping
      effect widely observed in graphene nanodevices. 

PMID- 24564735
TI  - pH-dependent transport of metal cations in porous media.
AB  - We study the effect of pH-dependent adsorption and hydrodynamic dispersion on
      cation transport through a reactive porous medium with a hydrophilic surface. We
      investigate how competitive adsorption between a proton and a metal (which in
      some situations of practical interest may also be a radionuclide) can facilitate
      the migration of a certain fraction of the latter. We performed laboratory
      experiments using a chromatographic column filled with silica beads coated with
      iron oxide and flooded initially with an acidic solution (pH ~ 3) and then with
      an alkaline solution (pH > 7) containing either sodium, potassium, lithium,
      calcium, magnesium, or barium. The composition of each injected solution was
      chosen to represent one of two possible theoretical predictions, either a
      retarded shock and a fast pulse, that is, traveling at the interstitial fluid
      velocity, or only a retarded shock. Highly resolved breakthrough curves measured
      with inline ion chromatography allowed us to observe in all cases agreement with
      theoretical predictions, including numerous observations of a fast pulse. The
      fast pulse is the result of the interaction between pH-dependent adsorption and
      hydrodynamic dispersion and has previously been observed in systems with
      strontium. Here, we show the fast pulse arises also in the case of other cations
      allowing a generalization of the physical mechanism underlying this phenomenon
      and consideration of it as a new fast transport behavior. A one-dimensional
      reactive transport model for an incompressible fluid was developed combining
      surface complexation with mass conservation equations for a solute and the
      acidity (difference between the total proton and hydroxide concentration). In all
      cases, the model agrees with the measurements capturing the underlying physics of
      the overall transport behavior. Our results suggest that the interplay between pH
      dependent adsorption and hydrodynamic dispersion can give rise to the rapid
      migration of metals through reactive porous media with potential effects on, for
      example, the performance of subsurface engineering infrastructures for pollutant
      containment, the mobilization of metal contaminants by brine acidified upon
      contact with CO2 during geologic carbon storage, and the chromatographic
      separation processes in industrial applications. 

PMID- 24564733
TI  - Coffee component hydroxyl hydroquinone (HHQ) as a putative ligand for PPAR gamma
      and implications in breast cancer.
AB  - BACKGROUND: Coffee contains several compounds that have the potential to
      influence breast cancer risk and survival. However, epidemiologic data on the
      relation between coffee compounds and breast cancer survival are sparse and
      inconsistent. RESULTS: We show that coffee component HHQ has significant
      apoptotic effect on MDA-MB-231 and MCF-7 cells in vitro, and that ROS generation,
      change in mitochondrial membrane permeability, upregulation of Bax and Caspase-8
      as well as down regulation of PGK1 and PKM2 expression may be important apoptosis
      inducing mechanisms. The results suggest that PPARgamma ligands may serve as
      potential therapeutic agents for breast cancer therapy. HHQ was also validated as
      a ligand for PPARgamma by docking procedure. CONCLUSION: This is the first report
      on the anti-breast cancer (in vitro) activity of HHQ.

PMID- 24564737
TI  - Putative biomarkers and therapeutic targets associated with radiation resistance.
AB  - Radiation therapy plays an important role in the management of malignant tumors,
      however, the problem of radiation resistance resulting in tumor recurrences after
      treatment is still unsolved. The emergence of novel biomarkers to predict cancer
      cell insensitivity to ionizing radiation could help to improve therapy results in
      cancer patients receiving radiation therapy. The proteomic approach could be
      effectively used to identify proteins associated with cancer radiation
      resistance. It is generally believed that radiation resistance could be
      associated with cancer stem cell persistence within the tumor. Therefore,
      determination of the molecular characteristics of cancer stem cells could provide
      additional possibilities to discover novel biomarkers to predict radiation
      resistance in cancer patients. This review addresses proteome-based findings that
      could be used for further biomarker identification and preclinical and clinical
      validation.

PMID- 24564739
TI  - A rapid one-step fabrication of patternable superhydrophobic surfaces driven by
      Marangoni instability.
AB  - We present a facile and inexpensive approach without any fluorinated chemistry to
      create superhydrophobic surface with exceptional liquid repellency,
      transportation of oil, selective capture of oil, optical bar code, and self
      cleaning. Here we show experimentally that the control of evaporation is
      important and can be used to form superhydrophobic surface driven by Marangoni
      instability: the method involves in-situ photopolymerization in the presence of a
      volatile solvent and porous PDMS cover to afford superhydrophobic surfaces with
      the desired combination of micro- and nanoscale roughness. The porous PDMS cover
      significantly affects Marangoni convection of coating fluid, inducing composition
      gradients at the same time. In addition, the change of concentration of ethanol
      is able to produce versatile surfaces from hydrophilic to superhydrophobic and as
      a consequence to determine contact angles as well as roughness factors. In
      conclusion, the control of evaporation under the polymerization provides a
      convenient parameter to fabricate the superhydrophobic surface, without
      application of fluorinated chemistry and the elegant nanofabrication technique. 

PMID- 24564736
TI  - Post genome-wide association studies functional characterization of prostate
      cancer risk loci.
AB  - BACKGROUND: Over the last decade, genome-wide association studies (GWAS) have
      discovered many risk associated single nucleotide polymorphisms (SNPs) of
      prostate cancer (PCa). However, the majority of the associated PCa SNPs,
      including those in linkage disequilibrium (LD) blocks, are generally not located
      in protein coding regions. The systematical investigation of the functional roles
      of these SNPs, especially the non-coding SNPs, becomes very necessary and helpful
      to the understanding of the molecular mechanism of PCa. RESULTS: In this work, we
      proposed a comprehensive framework at network level to integrate the SNP
      annotation, target gene assignment, gene ontology (GO) classification, pathway
      enrichment analysis and regulatory network reconstruction to illustrate the
      molecular functions of PCa associated SNPs. By LD expansion, we first identified
      1828 LD SNPs using 49 reported GWAS SNPs as a start. We carefully annotated these
      1828 LD SNPs via either UCSC known genes, UCSC regulation elements, or expression
      Quantitative Trait Loci (eQTL) data. As a result, we found 1154 SNPs were
      functionally annotated and obtained 205 unique PCa genes for further enrichment
      analysis. The enriched GO biological processes and pathways were found mainly
      related to regulation of cell death, apoptosis, cell proliferation, and metabolic
      process, which have been proved essential to cancer development. We constructed
      PCa genes specific transcription regulatory networks, finding several important
      genetic regulators for PCa, such as IGF-1/IGF-2 receptors, SP1, CREB1, and
      androgen receptor (AR). CONCLUSIONS: A comprehensive framework was proposed for
      integrative and systematic analysis of PCa SNPs, the analysis can provide
      essential information for the understanding of the regulatory function of GWAS
      SNPs in PCa, and will facilitate the discovery of novel candidate biomarkers for
      diagnosis and prognosis of PCa.

PMID- 24564740
TI  - Assessment of oculomotor control and balance post-concussion: a preliminary study
      for a novel approach to concussion management.
AB  - PRIMARY OBJECTIVE: Balance disturbances occur in ~30% of concussion injuries,
      with vestibular dysfunction reported as the main contributor. However, few have
      studied oculomotor control post-concussion to assess vestibular dysfunction.
      RESEARCH DESIGN: The current research measured the differences in oculomotor
      control between athletes post-concussion (PC) and athletes without concussion
      (NC) during an active balance control task. METHODS: Nine PC and nine NC athletes
      wore a monocular eye tracking device, while balance tests were performed using
      the Nintendo WiiFit(r) soccer heading game. Average game scores, eye deviations
      from centre (Gaze Deviations) and gaze fixation (Percentage Time on Centre) were
      measured. RESULTS: PC made significantly greater Gaze Deviations from centre
      compared to NC (p < 0.001), however Percentage Time on Centre and game scores
      were not significantly different between groups. Correlations between gaze and
      balance within groups revealed a significant positive correlation in NC, while a
      significant negative correlation in PC. CONCLUSIONS: Results from this
      exploratory examination of oculomotor behaviour post-concussion revealed
      significant differences in gaze stability between athletes with a concussion and
      those without, suggesting vestibular involvement post-concussion. Assessment of
      oculomotor control during balance activities may provide further insight into
      dysfunction of the vestibular system following a concussion injury.

PMID- 24564741
TI  - Electric-field control of ferromagnetism in Mn-doped ZnO nanowires.
AB  - In this Letter, the electric-field control of ferromagnetism was demonstrated in
      a back-gated Mn-doped ZnO (Mn-ZnO) nanowire (NW) field-effect transistor (FET).
      The ZnO NWs were synthesized by a thermal evaporation method, and the Mn doping
      of 1 atom % was subsequently carried out in a MBE system using a gas-phase
      surface diffusion process. Detailed structural analysis confirmed the single
      crystallinity of Mn-ZnO NWs and excluded the presence of any precipitates or
      secondary phases. For the transistor, the field-effect mobility and n-type
      carrier concentration were estimated to be 0.65 cm(2)/V.s and 6.82 * 10(18) cm(
      3), respectively. The magnetic hysteresis curves measured under different
      temperatures (T = 10-350 K) clearly demonstrate the presence of ferromagnetism
      above room temperature. It suggests that the effect of quantum confinements in
      NWs improves Tc, and meanwhile minimizes crystalline defects. The
      magnetoresistace (MR) of a single Mn-ZnO NW was observed up to 50 K. Most
      importantly, the gate modulation of the MR ratio was up to 2.5 % at 1.9 K, which
      implies the electric-field control of ferromagnetism in a single Mn-ZnO NW. 

PMID- 24564742
TI  - Highly sensitive low-background fluorescent probes for imaging of nitric oxide in
      cells and tissues.
AB  - Small-molecule fluorescent probes in combination with fluorescent microscopy can
      be a powerful tool to provide real-time detection and high spatiotemporal
      resolution of transient molecules in cells and bodies. For the design of
      fluorescent probes for transient molecule imaging, high detection sensitivity is
      crucial. In this report, two new fluorescent probes, 8-(3,4-diaminophenyl)-4,4
      difluoro-4-bora-3a,4a-diaza-di(1,2-dihydro)naphtho[b,g]-s-indacene (DANPBO-H) and
      8-(3,4-diaminophenyl)-1,7-dimethyl-4,4-difluoro-4-bora-3a,4a-diaza-di(1,2
      dihydro)naphtho[b,g]-s-indacene (DANPBO-M), have been developed for nitric oxide
      (NO) imaging. The detection sensitivity has been efficiently improved by use of
      these probes through increasing NO detection signals and decreasing background
      fluorescence. Fluorescence in the far-red region is enhanced by 400- and 550-fold
      after reaction with NO is achieved and remains stable for at least 24 h under the
      irradiation of xenon lamp. Excitation and emission wavelengths longer than 600 nm
      and excellent intracellular retention of these probes and their NO products
      create dark background inside and outside cells and tissues. What is more, the
      excellent intracellular retention of these compounds is obtained by their strong
      lipophilicity, which is a novel design concept diametrically opposite to the
      traditional approaches. The high sensitivity and dark background make DANPBO-H
      and DANPBO-M competitive for NO imaging in cells and tissues. The lipophilicity
      based intracellular retention mechanism as a design strategy has great potential
      in the development of fluorescent probes for bioimaging. 

PMID- 24564743
TI  - Determination of phosphine in plant materials: method optimization and validation
      in interlaboratory comparison tests.
AB  - The optimization and validation of a method for the determination of phosphine in
      plant materials are described. The method is based on headspace sampling over the
      sample heated in 5% sulfuric acid. Critical factors such as sample amount,
      equilibration conditions, method of quantitation, and matrix effects are
      discussed, and validation data are presented. Grinding of coarse samples does not
      lead to lower results and is a prerequisite for standard addition experiments,
      which present the most reliable approach for quantitation because of notable
      matrix effects. Two interlaboratory comparisons showed that results varied
      considerably and that an uncertainty of measurement of about 50% has to be
      assessed. Flame photometric and mass spectrometric detection gave similar
      results. The proposed method is well reproducible within one laboratory, and
      results from the authors' laboratories using different injection and detection
      techniques are very close to each other. The considerable variation in the
      interlaboratory comparison shows that this analysis is still challenging in
      practice and further proficiency testing is needed. 

PMID- 24564744
TI  - Prediction of heterotrimeric protein complexes by two-phase learning using
      neighboring kernels.
AB  - BACKGROUND: Protein complexes play important roles in biological systems such as
      gene regulatory networks and metabolic pathways. Most methods for predicting
      protein complexes try to find protein complexes with size more than three. It,
      however, is known that protein complexes with smaller sizes occupy a large part
      of whole complexes for several species. In our previous work, we developed a
      method with several feature space mappings and the domain composition kernel for
      prediction of heterodimeric protein complexes, which outperforms existing
      methods. RESULTS: We propose methods for prediction of heterotrimeric protein
      complexes by extending techniques in the previous work on the basis of the idea
      that most heterotrimeric protein complexes are not likely to share the same
      protein with each other. We make use of the discriminant function in support
      vector machines (SVMs), and design novel feature space mappings for the second
      phase. As the second classifier, we examine SVMs and relevance vector machines
      (RVMs). We perform 10-fold cross-validation computational experiments. The
      results suggest that our proposed two-phase methods and SVM with the extended
      features outperform the existing method NWE, which was reported to outperform
      other existing methods such as MCL, MCODE, DPClus, CMC, COACH, RRW, and PPSampler
      for prediction of heterotrimeric protein complexes. CONCLUSIONS: We propose two
      phase prediction methods with the extended features, the domain composition
      kernel, SVMs and RVMs. The two-phase method with the extended features and the
      domain composition kernel using SVM as the second classifier is particularly
      useful for prediction of heterotrimeric protein complexes.

PMID- 24564745
TI  - Influence of HumDN1 VNTR polymorphism on DNASE1 expression in systemic lupus
      erythematosus and rheumatoid arthritis.
AB  - The purpose of this study was to analyze the effect of the HumDN1 VNTR
      polymorphism on DNASE1 mRNA expression and enzyme activity in lupus (SLE) and
      rheumatoid arthritis (RA) compared to healthy control (HC). Kuwait subjects (n =
      500) matched by age/gender/ethnicity were genotyped by fragment-analysis. DNASE1
      expression was analysed using quantitative Real-Time-PCR and sera from subjects
      were screened for DNase1 reduction activity by ELISA. Allele and genotype
      distribution of HumDN1 VNTR revealed a significant association with
      susceptibility to SLE and RA (p < 0.05, OR > 1). Relative expression analysis
      revealed a significant increase in DNASE1 mRNA in SLE (p = 0.0001) and RA (p =
      0.002) compared to HC. Stratification of subjects revealed, increased DNASE1
      expression in SLE with 5/5 (p = 0.0001), 3/4 (p = 0.0001) and 3/5 genotype (p =
      0.01). A reduction in DNASE1 expression was specifically observed in SLE with 4,4
      genotype (p = 0.0004). RA patients with 3/4 genotype (p = 0.02) showed a
      significant increase in DNASE1 expression. Similarly a significant association
      was observed between DNase1 reduction activity and SLE (p = 0.0001). SLE patients
      with 3,4 (p = 0.0001) and 5,5 genotype (p = 0.0001) showed increased DNase1
      reduction activity, while a lack of association was observed with RA. The present
      study is the first to reveal the effect of HumDN1 VNTR on DNASE1 expression in
      SLE and RA.

PMID- 24564738
TI  - ALS Multicenter Cohort Study of Oxidative Stress (ALS COSMOS): study methodology,
      recruitment, and baseline demographic and disease characteristics.
AB  - Abstract In a multicenter study of newly diagnosed ALS patients without a
      reported family history of ALS, we are prospectively investigating whether
      markers of oxidative stress (OS) are associated with disease progression. Methods
      utilize an extensive structured telephone interview ascertaining environmental,
      lifestyle, dietary and psychological risk factors associated with OS. Detailed
      assessments were performed at baseline and at 3-6 month intervals during the
      ensuing 30 months. Our biorepository includes DNA, plasma, urine, and skin. Three
      hundred and fifty-five patients were recruited. Subjects were enrolled over a 36
      month period at 16 sites. To meet the target number of subjects, the recruitment
      period was prolonged and additional sites were included. Results showed that
      demographic and disease characteristics were similar between 477 eligible/non
      enrolled and enrolled patients, the only difference being type of health
      insurance among enrolled patients. Sites were divided into three groups by the
      number of enrolled subjects. Comparing these three groups, the Columbia site had
      fewer 'definite ALS' diagnoses. This is the first prospective, interdisciplinary,
      in-depth, multicenter epidemiological investigation of OS related to ALS
      progression and has been accomplished by an aggressive recruitment process. The
      baseline demographic and disease features of the study sample are now fully
      characterized. 

PMID- 24564746
TI  - Maternal positioning to correct occipito-posterior fetal position in labour: a
      randomised controlled trial.
AB  - BACKGROUND: The occipito-posterior (OP) fetal head position during the first
      stage of labour occurs in 10-34% of cephalic presentations. Most will spontaneous
      rotate in anterior position before delivery, but 5-8% of all births will persist
      in OP position for the third stage of labour. Previous observations have shown
      that this can lead to an increase of complications, such as an abnormally long
      labour, maternal and fetal exhaustion, instrumental delivery, severe perineal
      tears, and emergency caesarean section. Usual care in the case of diagnosis of OP
      position is an expectant management. However, maternal postural techniques have
      been reported to promote the anterior position of the fetal head for delivery. A
      Cochrane review reported that these maternal positions are well accepted by women
      and reduce back pain. However, the low sample size of included studies did not
      allow concluding on their efficacy on delivery outcomes, particularly those
      related to persistent OP position. Our objective is to evaluate the efficacy of
      maternal position in the management of OP position during the first stage of
      labour. METHODS/DESIGN: A randomised clinical trial is ongoing in the maternity
      unit of the Geneva University Hospitals, Geneva, Switzerland. The unit is the
      largest in Switzerland with 4,000 births/year. The trial will involve 438 women
      with a fetus in OP position, confirmed by sonography, during the first stage of
      the labour. The main outcome measure is the position of the fetal head, diagnosed
      by ultrasound one hour after randomisation. DISCUSSION: It is important to
      evaluate the efficacy of maternal position to correct fetal OP position during
      the first stage of the labour. Although these positions seem to be well accepted
      by women and appear easy to implement in the delivery room, the sample size of
      the last randomised clinical trial published in 2005 to evaluate this
      intervention had insufficient power to demonstrate clear evidence of
      effectiveness. If the technique demonstrates efficacy, it would reduce the
      physical and psychological consequences of complications at birth related to
      persistent OP position. TRIAL REGISTRATION: ClinicalTrials.gov,
      http://www.clinicaltrials.gov: (no. NCT01291355).

PMID- 24564747
TI  - Validity, reliability, and responsiveness of the Self-reported Foot and Ankle
      Score (SEFAS) in forefoot, hindfoot, and ankle disorders.
AB  - BACKGROUND AND PURPOSE: The self-reported foot and ankle score (SEFAS) is a
      questionnaire designed to evaluate disorders of the foot and ankle, but it is
      only validated for arthritis in the ankle. We validated SEFAS in patients with
      forefoot, midfoot, hindfoot, and ankle disorders. PATIENTS AND METHODS: 118
      patients with forefoot disorders and 106 patients with hindfoot or ankle
      disorders completed the SEFAS, the foot and ankle outcome score (FAOS), SF-36,
      and EQ-5D before surgery. We evaluated construct validity for SEFAS versus FAOS,
      SF-36, and EQ-5D; floor and ceiling effects; test-retest reliability (ICC);
      internal consistency; and agreement. Responsiveness was evaluated by effect size
      (ES) and standardized response mean (SRM) 6 months after surgery. The analyses
      were done separately in patients with forefoot disorders and hindfoot/ankle
      disorders. RESULTS: Comparing SEFAS to the other scores, convergent validity
      (when correlating foot-specific questions) and divergent validity (when
      correlating foot-specific and general questions) were confirmed. SEFAS had no
      floor and ceiling effects. In patients with forefoot disorders, ICC was 0.92 (CI:
      0.85-0.96), Cronbach's alpha was 0.84, ES was 1.29, and SRM was 1.27. In patients
      with hindfoot or ankle disorders, ICC was 0.93 (CI: 0.88-0.96), Cronbach's alpha
      was 0.86, ES was 1.05, and SRM was 0.99. INTERPRETATION: SEFAS has acceptable
      validity, reliability, and responsiveness in patients with various forefoot,
      hindfoot, and ankle disorders. SEFAS is therefore an appropriate patient-
      reported outcome measure (PROM) for these patients, even in national registries.

PMID- 24564748
TI  - Efficacy of a novel PCR- and microarray-based method in diagnosis of a prosthetic
      joint infection.
AB  - BACKGROUND AND PURPOSE: Polymerase chain reaction (PCR) methods enable detection
      and species identification of many pathogens. We assessed the efficacy of a new
      PCR and microarray-based platform for detection of bacteria in prosthetic joint
      infections (PJIs). METHODS: This prospective study involved 61 suspected PJIs in
      hip and knee prostheses and 20 negative controls. 142 samples were analyzed by
      Prove-it Bone and Joint assay. The laboratory staff conducting the Prove-it
      analysis were not aware of the results of microbiological culture and clinical
      findings. The results of the analysis were compared with diagnosis of PJIs
      defined according to the Musculoskeletal Infection Society (MSIS) criteria and
      with the results of microbiological culture. RESULTS: 38 of 61 suspected PJIs met
      the definition of PJI according to the MSIS criteria. Of the 38 patients, the PCR
      detected bacteria in 31 whereas bacterial culture was positive in 28 patients. 15
      of the PJI patients were undergoing antimicrobial treatment as the samples for
      analysis were obtained. When antimicrobial treatment had lasted 4 days or more,
      PCR detected bacteria in 6 of the 9 patients, but positive cultures were noted in
      only 2 of the 9 patients. All PCR results for the controls were negative. Of the
      61 suspected PJIs, there were false-positive PCR results in 6 cases.
      INTERPRETATION: The Prove-it assay was helpful in PJI diagnostics during ongoing
      antimicrobial treatment. Without preceding treatment with antimicrobials, PCR and
      microarray-based assay did not appear to give any additional information over
      culture.

PMID- 24564749
TI  - The effect of femoral offset modification on gait after total hip arthroplasty.
AB  - BACKGROUND AND PURPOSE: A decrease of 15% in femoral offset (FO) has been
      reported to generate a weakness of the abductor muscle, but this has not been
      directly linked to an alteration of gait. Our hypothesis was that this 15%
      decrease in FO may also generate a clinically detectable alteration in the gait.
      PATIENTS AND METHODS: We performed a prospective comparative study on 28 patients
      who underwent total hip arthroplasty (THA) for unilateral primary osteoarthritis.
      The 3D hip anatomy was analyzed preoperatively and postoperatively. 3 groups were
      defined according to the alteration in FO following surgery: a minimum decrease
      of 15% (9 patients), restored (14), and a minimum increase of 15% (5). A gait
      analysis was performed at 1-year follow-up using an ambulatory device. Each limb
      was compared to the contralateral healthy limb. RESULTS: In contrast to the
      "restored" group and the "increased" group, in the "decreased" group there was a
      statistically significant asymmetry between sides, with reduced range of motion
      and a lower maximal swing speed on the operated side. INTERPRETATION: A decrease
      in FO of 15% or more after THA leads to an alteration in the gait. We recommend 3
      D preoperative planning because the FO may be underestimated by up to 20% on
      radiographs and it may therefore not be restored, with clinical consequences.

PMID- 24564751
TI  - Hierarchical structure and physicochemical properties of plasticized chitosan.
AB  - Plasticized chitosan with hierarchical structure, including multiple length scale
      structural units, was prepared by a "melt"-based method, that is,
      thermomechanical mixing, as opposed to the usual casting-evaporation procedure.
      Chitosan was successfully plasticized by thermomechanical mixing in the presence
      of concentrated lactic acid and glycerol using a batch mixer. Different
      plasticization formulations were compared in this study, in which concentrated
      lactic acid was used as protonation agent as well as plasticizer. The
      microstructure of thermomechanically plasticized chitosan was investigated by X
      ray diffraction, scanning electron microscopy, and optical microscopy. With
      increasing amount of additional plasticizers (glycerol or water), the
      crystallinity of the plasticized chitosan decreased from 63.7% for the original
      chitosan powder to almost zero for the sample plasticized with additional water.
      Salt linkage between lactic acid molecules and amino side chains of chitosan was
      confirmed by FTIR spectroscopy: the lactic acid molecules expanded the space
      between the chitosan molecules of the crystalline phase. In the presence of other
      plasticizers (glycerol and water), various levels of structural units including
      an amorphous phase, nanofibrils, nanofibril clusters, and microfibers were
      produced under mechanical shear and thermal energy and identified for the first
      time. The thermal and thermomechanical properties of the plasticized chitosan
      were measured by thermogravimetric analysis, differential scanning calorimetric,
      and DMA. These properties were correlated with the different levels of
      microstructure, including multiple structural units. 

PMID- 24564750
TI  - A single topical dose of erythropoietin applied on a collagen carrier enhances
      calvarial bone healing in pigs.
AB  - BACKGROUND AND PURPOSE: The osteogenic potency of erythropoietin (EPO) has been
      documented. However, its efficacy in a large-animal model has not yet been
      investigated; nor has a clinically safe dosage. The purpose of this study was to
      overcome such limitations of previous studies and thereby pave the way for
      possible clinical application. Our hypothesis was that EPO increases calvarial
      bone healing compared to a saline control in the same subject. METHODS: We used a
      porcine calvarial defect model. In each of 18 pigs, 6 cylindrical defects
      (diameter: 1 cm; height: 1 cm) were drilled, allowing 3 pairwise comparisons.
      Treatment consisted of either 900 IU/mL EPO or an equal volume of saline in
      combination with either autograft, a collagen carrier, or a polycaprolactone
      (PCL) scaffold. After an observation time of 5 weeks, the primary outcome (bone
      volume fraction (BV/TV)) was assessed with high-resolution quantitative computed
      tomography. Secondary outcome measures were histomorphometry and blood samples.
      RESULTS: The median BV/TV ratio of the EPO-treated collagen group was 1.06 (CI:
      1.02-1.11) relative to the saline-treated collagen group. Histomorphometry showed
      a similar median effect size, but it did not reach statistical significance.
      Autograft treatment had excellent healing potential and was able to completely
      regenerate the bone defect independently of EPO treatment. Bony ingrowth into the
      PCL scaffold was sparse, both with and without EPO. Neither a substantial
      systemic effect nor adverse events were observed. The number of blood vessels was
      similar in EPO-treated defects and saline-treated defects. INTERPRETATION:
      Topical administration of EPO on a collagen carrier moderately increased bone
      healing. The dosing regime was safe, and could have possible application in the
      clinical setting. However, in order to increase the clinical relevance, a more
      potent but still clinically safe dose should be investigated.

PMID- 24564752
TI  - Bridging the gap between preventive and restorative dentistry: identification of
      caries risk factors and strategies for minimizing risk.
AB  - Following the introduction of CAMBRA (Caries Management by Risk Assessment) in
      2007, a number of recommendations for office protocols were introduced, and many
      companies have formulated products and procedures for implementing CAMBRA. As a
      result, the implementation of a caries management program can be confounding and
      overwhelming to a dental practitioner. Understanding risk factors as they
      contribute to the caries process can help mitigate confusion and guide the
      practitioner when selecting materials for their practice. Ultimately, knowing how
      the risk factors play a role in the progression of dental caries will lead to
      appropriate risk management and product recommendations. The purpose of this
      article is to discuss the contribution of risk factors to the caries process and
      to introduce strategies that restorative dentists can utilize to minimize caries
      risk. 

PMID- 24564753
TI  - The dentist's role in diagnosis and treatment of halitosis.
AB  - Halitosis, or oral malodor, affects 50 percent of the adult population. Dental
      professionals can be a key resource for patients seeking treatment. It is
      important that dentists and hygienists are able to appropriately diagnose
      halitosis and understand the various etiologies that cause this condition before
      deciding on an individualized treatment plan. The aim of this article is to
      review the etiologies of and methods to diagnose halitosis. Various treatment
      options are described, including an individualized plan and indications for
      referral to other healthcare professionals. 

PMID- 24564754
TI  - One abutment-one time: the negative effect of uncontrolled abutment margin depths
      and excess cement--a case report.
AB  - It has been reported that repeated connection and disconnection of transmucosal
      components stimulates apical repositioning of the soft tissues and marginal bone
      resorption. Limiting the number of times this occurs may be beneficial. A new
      treatment concept called one abutment one time describes the placement of the
      definitive abutment at the time of surgery. This case highlights the
      susceptibility of excess cement residue associated with this concept and
      unesthetic outcome even when meticulous surgical correction is attempted. 

PMID- 24564755
TI  - "Training teeth": transitional resin bonding for diagnostic purposes.
AB  - Despite the best diagnostic efforts, the etiology of a patient's dental disease
      may remain elusive. Without knowing the underlying disease factors, predictable
      outcomes are difficult to obtain. This case report describes the diagnosis and
      treatment of a patient who felt embarrassed by the appearance of his smile and
      was desperately seeking a solution. Despite meticulous data collection and a
      systematic diagnostic approach, the disease etiology could not be determined. It
      was, therefore, decided to treat the patient with non-invasive transitional
      directly bonded composite to road test his new teeth. In this way, a
      determination could be made as to whether they would function successfully over
      time. 

PMID- 24564756
TI  - Retrieval of a defective cement-retained implant prosthesis.
AB  - As the popularity of cement-retained implant prosthetics grows, so, too, does the
      need for retreatment. The predictable removal of cement-retained implant crowns
      has often proven difficult due to a multitude of variables, including locating
      the access and stripped screws. The techniques discussed in this article address
      these issues, thus simplifying the retreatment process. 

PMID- 24564757
TI  - Adhesive dentistry: 2013 and into the future.
AB  - With the recent founding of the International Academy for Adhesive Dentistry
      (IAAD), scientific research, commercially available products, and clinically
      proven protocols will be brought together with the dental profession. 

PMID- 24564758
TI  - Mapping proteins in the presence of paralogs using units of coevolution.
AB  - BACKGROUND: We study the problem of mapping proteins between two protein families
      in the presence of paralogs. This problem occurs as a difficult subproblem in
      coevolution-based computational approaches for protein-protein interaction
      prediction. RESULTS: Similar to prior approaches, our method is based on the idea
      that coevolution implies equal rates of sequence evolution among the interacting
      proteins, and we provide a first attempt to quantify this notion in a formal
      statistical manner. We call the units that are central to this quantification
      scheme the units of coevolution. A unit consists of two mapped protein pairs and
      its score quantifies the coevolution of the pairs. This quantification allows us
      to provide a maximum likelihood formulation of the paralog mapping problem and to
      cast it into a binary quadratic programming formulation. CONCLUSION: CUPID, our
      software tool based on a Lagrangian relaxation of this formulation, makes it, for
      the first time, possible to compute state-of-the-art quality pairings in a few
      minutes of runtime. In summary, we suggest a novel alternative to the earlier
      available approaches, which is statistically sound and computationally feasible.

PMID- 24564760
TI  - Distilling structure in Taverna scientific workflows: a refactoring approach.
AB  - BACKGROUND: Scientific workflows management systems are increasingly used to
      specify and manage bioinformatics experiments. Their programming model appeals to
      bioinformaticians, who can use them to easily specify complex data processing
      pipelines. Such a model is underpinned by a graph structure, where nodes
      represent bioinformatics tasks and links represent the dataflow. The complexity
      of such graph structures is increasing over time, with possible impacts on
      scientific workflows reuse. In this work, we propose effective methods for
      workflow design, with a focus on the Taverna model. We argue that one of the
      contributing factors for the difficulties in reuse is the presence of "anti
      patterns", a term broadly used in program design, to indicate the use of
      idiomatic forms that lead to over-complicated design. The main contribution of
      this work is a method for automatically detecting such anti-patterns, and
      replacing them with different patterns which result in a reduction in the
      workflow's overall structural complexity. Rewriting workflows in this way will be
      beneficial both in terms of user experience (easier design and maintenance), and
      in terms of operational efficiency (easier to manage, and sometimes to exploit
      the latent parallelism amongst the tasks). RESULTS: We have conducted a thorough
      study of the workflows structures available in Taverna, with the aim of finding
      out workflow fragments whose structure could be made simpler without altering the
      workflow semantics. We provide four contributions. Firstly, we identify a set of
      anti-patterns that contribute to the structural workflow complexity. Secondly, we
      design a series of refactoring transformations to replace each anti-pattern by a
      new semantically-equivalent pattern with less redundancy and simplified
      structure. Thirdly, we introduce a distilling algorithm that takes in a workflow
      and produces a distilled semantically-equivalent workflow. Lastly, we provide an
      implementation of our refactoring approach that we evaluate on both the public
      Taverna workflows and on a private collection of workflows from the BioVel
      project. CONCLUSION: We have designed and implemented an approach to improving
      workflow structure by way of rewriting preserving workflow semantics. Future work
      includes considering our refactoring approach during the phase of workflow design
      and proposing guidelines for designing distilled workflows.

PMID- 24564759
TI  - Ischemia modified albumin increase indicating cardiac damage after experimental
      subarachnoid hemorrhage.
AB  - BACKGROUND: Cardiac complications are often developed after subarachnoid
      hemorrhage (SAH) and may cause sudden death of the patient. There are reports in
      the literature addressing ischemia modified albumin (IMA) as an early and useful
      marker in the diagnosis of ischemic heart events. The aim of this study is to
      evaluate serum IMA by using the albumin cobalt binding (ACB) test in the first,
      second, and seventh days of experimental SAH in rats.Twenty-eight Wistar albino
      rats were divided into four groups each consisting of seven animals. These were
      classified as control group, 1st, 2nd and 7th day SAH groups. SAH was done by
      transclival basilar artery puncture. Blood samples were collected under
      anesthesia from the left ventricles of the heart using the cardiac puncture
      method for IMA measurement. Histopathological examinations were performed on the
      heart and lung tissues. Albumin with by colorimetric, creatine kinase (CK),
      aspartate aminotransferase (AST), lactate dehydrogenase (LDH) were determined on
      an automatic analyser using the enzymatic method. IMA using by ACB test was
      detected with spectrophotometer. RESULTS: Serum IMA (p = 0.044) in seventh day of
      SAH were higher compared to the control group. Total injury scores of heart and
      lung tissue, also myocytolysis at day 7 were significantly higher than control
      group (p = 0.001, p = 0.001, p = 0.001), day 1 (p = 0.001, p = 0.001, p = 0.001)
      and day 2 (p = 0.001, p = 0.007, p = 0.001). A positive correlation between IMA -
      myocytolysis (r = 0.48, p = 0.008), and between IMA - heart tissue total injury
      score (r = 0.41, p = 0.029) was found. CONCLUSION: The results revealed that
      increased serum IMA may be related to myocardial stress after SAH.

PMID- 24564761
TI  - Feasibility and validity of the structured attention module among economically
      disadvantaged preschool-age children.
AB  - Rooted in the theory of attention put forth by Mirsky, Anthony, Duncan, Ahearn,
      and Kellam (1991), the Structured Attention Module (SAM) is a developmentally
      sensitive, computer-based performance task designed specifically to assess
      sustained selective attention among 3- to 6-year-old children. The current study
      addressed the feasibility and validity of the SAM among 64 economically
      disadvantaged preschool-age children (mean age = 58 months; 55% female); a
      population known to be at risk for attention problems and adverse math
      performance outcomes. Feasibility was demonstrated by high completion rates and
      strong associations between SAM performance and age. Principal Factor Analysis
      with rotation produced robust support for a three-factor model (Accuracy, Speed,
      and Endurance) of SAM performance, which largely corresponded with existing
      theorized models of selective and sustained attention. Construct validity was
      evidenced by positive correlations between SAM Composite scores and all three SAM
      factors and IQ, and between SAM Accuracy and sequential memory. Value-added
      predictive validity was not confirmed through main effects of SAM on math
      performance above and beyond age and IQ; however, significant interactions by
      child sex were observed: Accuracy and Endurance both interacted with child sex to
      predict math performance. In both cases, the SAM factors predicted math
      performance more strongly for girls than for boys. There were no overall sex
      differences in SAM performance. In sum, the current findings suggest that
      interindividual variation in sustained selective attention, and potentially other
      aspects of attention and executive function, among young, high-risk children can
      be captured validly with developmentally sensitive measures.

PMID- 24564762
TI  - Identifying conserved protein complexes between species by constructing interolog
      networks.
AB  - BACKGROUND: Protein complexes conserved across species indicate processes that
      are core to cellular machinery (e.g. cell-cycle or DNA damage-repair complexes
      conserved across human and yeast). While numerous computational methods have been
      devised to identify complexes from the protein interaction (PPI) networks of
      individual species, these are severely limited by noise and errors (false
      positives) in currently available datasets. Our analysis using human and yeast
      PPI networks revealed that these methods missed several important complexes
      including those conserved between the two species (e.g. the MLH1-MSH2-PMS2-PCNA
      mismatch-repair complex). Here, we note that much of the functionalities of yeast
      complexes have been conserved in human complexes not only through sequence
      conservation of proteins but also of critical functional domains. Therefore,
      integrating information of domain conservation might throw further light on
      conservation patterns between yeast and human complexes. RESULTS: We identify
      conserved complexes by constructing an interolog network (IN) leveraging on the
      functional conservation of proteins between species through domain conservation
      (from Ensembl) in addition to sequence similarity. We employ 'state-of-the-art'
      methods to cluster the interolog network, and map these clusters back to the
      original PPI networks to identify complexes conserved between the species.
      Evaluation of our IN-based approach (called COCIN) on human and yeast interaction
      data identifies several additional complexes (76% recall) compared to direct
      complex detection from the original PINs (54% recall). Our analysis revealed that
      the IN-construction removes several non-conserved interactions many of which are
      false positives, thereby improving complex prediction. In fact removing non
      conserved interactions from the original PINs also resulted in higher number of
      conserved complexes, thereby validating our IN-based approach. These complexes
      included the mismatch repair complex, MLH1-MSH2-PMS2-PCNA, and other important
      ones namely, RNA polymerase-II, EIF3 and MCM complexes, all of which constitute
      core cellular processes known to be conserved across the two species.
      CONCLUSIONS: Our method based on integrating domain conservation and sequence
      similarity to construct interolog networks helps to identify considerably more
      conserved complexes between the PPI networks from two species compared to direct
      complex prediction from the PPI networks. We observe from our experiments that
      protein complexes are not conserved from yeast to human in a straightforward way,
      that is, it is not the case that a yeast complex is a (proper) sub-set of a human
      complex with a few additional proteins present in the human complex. Instead
      complexes have evolved multifold with considerable re-organization of proteins
      and re-distribution of their functions across complexes. This finding can have
      significant implications on attempts to extrapolate other kinds of relationships
      such as synthetic lethality from yeast to human, for example in the
      identification of novel cancer targets. AVAILABILITY:
      http://www.comp.nus.edu.sg/~leonghw/COCIN/.

PMID- 24564763
TI  - Calculating the diffusive flux of persistent organic pollutants between sediments
      and the water column on the Palos Verdes shelf superfund site using polymeric
      passive samplers.
AB  - Passive samplers were deployed to the seafloor at a marine Superfund site on the
      Palos Verdes Shelf, California, USA, and used to determine water concentrations
      of persistent organic pollutants (POPs) in the surface sediments and near-bottom
      water. A model of Fickian diffusion across a thin water boundary layer at the
      sediment-water interface was used to calculate flux of contaminants due to
      molecular diffusion. Concentrations at four stations were used to calculate the
      flux of DDE, DDD, DDMU, and selected PCB congeners from sediments to the water
      column. Three passive sampling materials were compared: PE strips, POM strips,
      and SPME fibers. Performance reference compounds (PRCs) were used with PE and POM
      to correct for incomplete equilibration, and the resulting POP concentrations,
      determined by each material, agreed within 1 order of magnitude. SPME fibers,
      without PRC corrections, produced values that were generally much lower (1 to 2
      orders of magnitude) than those measured using PE and POM, indicating that SPME
      may not have been fully equilibrated with waters being sampled. In addition,
      diffusive fluxes measured using PE strips at stations outside of a pilot remedial
      sand cap area were similar to those measured at a station inside the capped area:
      240 to 260 ng cm(-2) y(-1) for p,p'-DDE. The largest diffusive fluxes of POPs
      were calculated at station 8C, the site where the highest sediment concentrations
      have been measured in the past, 1100 ng cm(-2) y(-1) for p,p'-DDE. 

PMID- 24564765
TI  - Physicochemical properties of collagen solutions cross-linked by glutaraldehyde.
AB  - The physicochemical properties of collagen solutions (5 mg/ml) cross-linked by
      various amounts of glutaraldehyde (GTA) [GTA/collagen (w/w) = 0-0.5] under acidic
      condition (pH 4.00) were examined. Based on the results of the determination of
      residual amino group content, sodium dodecyl sulphate-polyacrylamide gel
      electrophoresis, dynamic rheological measurements, differential scanning
      calorimetry and atomic force microscopy (AFM), it was proved that the collagen
      solutions possessed strikingly different physicochemical properties depending on
      the amount of GTA. At low GTA amounts [GTA/collagen (w/w) <= 0.1], the residual
      amino group contents of the cross-linked collagens decreased largely from 100% to
      32.76%, accompanied by an increase in the molecular weight. Additionally,
      increases of the fiber diameter and the values of G', G" and eta* were measured,
      while the thermal denaturation temperature (Td) did not change visibly and the
      fluidity of collagen samples was still retained with increasing the GTA amount.
      When the ratio of GTA to collagen exceeded 0.1, although the residual amino group
      content only decreased by ~8.2%, the cross-linked collagen solution [GTA/collagen
      (w/w) = 0.3] displayed a clear loss of flow and a sudden rise (~2.0  degrees C)
      of the Td value compared to the uncross-linked collagen solution, probably
      illustrating that the collagen solution was converted into a gel with mature
      network structure-containing nuclei observed in AFM image. It was conjectured
      that the physicochemical properties of the collagen solutions might be in
      connection with the cross-linking between collagen molecules from the same
      aggregate or different aggregates.

PMID- 24564766
TI  - Attention deficit hyperactivity disorder as a risk factor for concussions in NCAA
      division-I athletes.
AB  - OBJECTIVE: Sports-related concussions are associated with both acute and long
      term consequences. Past work has identified novel risk factors and modifiers for
      concussions, including mood and neuropsychiatric disorders. Attention Deficit
      Hyperactivity Disorder (ADHD) is a common neuropsychiatric disorder that may also
      contribute to concussion risk, although no study has examined this possibility.
      METHODS: One hundred and thirty-nine NCAA Division-I athletes at Kent State
      University (KSU) self-reported a history of prior concussion and diagnostic
      history of ADHD as part of a larger concussion management programme at KSU.
      RESULTS: ADHD was prevalent (10.1%) and 18.0% of the sample reported a prior
      history of at least one concussion injury. 50.4% of athletes with ADHD reported a
      history of at least one prior concussion vs 14.4% of athletes without ADHD, which
      represented a significant difference (p < 0.01). Analyses showed that athletes
      with ADHD were more likely to report a past history of concussions than those
      without ADHD (F (1,133) = 4.31, p = 0.04). CONCLUSION: ADHD is prevalent in NCAA
      Division-I athletes and associated with history of past concussions. If
      replicated, these findings could have important implications in the prevention
      and management of concussions in athletes with ADHD.

PMID- 24564764
TI  - Control of household air pollution for child survival: estimates for intervention
      impacts.
AB  - BACKGROUND: Exposure to household air pollution (HAP) from cooking with solid
      fuels affects 2.8 billion people in developing countries, including children and
      pregnant women. The aim of this review is to propose intervention estimates for
      child survival outcomes linked to HAP. METHODS: Systematic reviews with meta
      analysis were conducted for ages 0-59 months, for child pneumonia, adverse
      pregnancy outcomes, stunting and all-cause mortality. Evidence for each outcome
      was assessed against Bradford-Hill viewpoints, and GRADE used for certainty about
      intervention effect size for which all odds ratios (OR) are presented as
      protective effects. RESULTS: Reviews found evidence linking HAP exposure with
      child ALRI, low birth weight (LBW), stillbirth, preterm birth, stunting and all
      cause mortality. Most studies were observational and rated low/very low in GRADE
      despite strong causal evidence for some outcomes; only one randomised trial was
      eligible.Intervention effect (OR) estimates of 0.64 (95% CI: 0.55, 0.75) for
      ALRI, 0.71 (0.65, 0.79) for LBW and 0.66 (0.54, 0.81) for stillbirth are
      proposed, specific outcomes for which causal evidence was sufficient. Exposure
      response evidence suggests this is a conservative estimate for ALRI risk
      reduction expected with sustained, low exposure. Statistically significant
      protective ORs were also found for stunting [OR=0.79 (0.70, 0.89)], and in one
      study of pre-term birth [OR=0.70 (0.54, 0.90)], indicating these outcomes would
      also likely be reduced. Five studies of all-cause mortality had an OR of 0.79
      (0.70, 0.89), but heterogenity precludes a reliable estimate for mortality
      impact. Although interventions including clean fuels and improved solid fuel
      stoves are available and can deliver low exposure levels, significant challenges
      remain in achieving sustained use at scale among low-income households.
      CONCLUSIONS: Reducing exposure to HAP could substantially reduce the risk of
      several child survival outcomes, including fatal pneumonia, and the proposed
      effects could be achieved by interventions delivering low exposures. Larger
      impacts are anticipated if WHO air quality guidelines are met. To achieve these
      benefits, clean fuels should be adopted where possible, and for other households
      the most effective solid fuel stoves promoted. To strengthen evidence, new
      studies with thorough exposure assessment are required, along with evaluation of
      the longer-term acceptance and impacts of interventions.

PMID- 24564767
TI  - Investigation of change in surface area and grain size of cadmium titanate
      nanofibers upon annealing and their effect on oxygen sensing.
AB  - We have investigated the phase changes in CdTiO3 nanofibers as the annealing
      temperature of nanofibers was increased from 600 to 1200  degrees C. The
      nanofibers annealed at 600  degrees C were ilmenite with a very small amount of
      CdO. Upon annealing at 950  degrees C, CdO was completely removed. Annealing at
      1000  degrees C yielded pure perovskite nanofibers, and at temperatures above
      1100  degrees C rutile TiO2 nanofibers were obtained. Brunauer-Emmett-Teller
      (BET) analysis showed that with increase in annealing temperature the surface
      area of nanofibers was decreased. The nanofibers annealed at 600  degrees C have
      the higher surface area of ~9.41 m(2)/g. Then oxygen sensors using CdTiO3
      nanofibers annealed at 600  degrees C (ilmenite) and 1000  degrees C (perovskite)
      were fabricated. The sensitivity of the ilmenite nanofibers sensor was 2 times
      than that of the perovskite nanofibers sensor. The response and recovery times
      were 120 and 23 s, respectively, for the ilmenite nanofibers sensor, whereas
      response and recovery times were 156 and 50 s, respectively, for the perovskite
      nanofibers sensor. Better oxygen characteristics of ilmenite nanofibers are
      attributed to their large surface area and porosity. Therefore, we believe that
      ilmenite CdTiO3 nanofibers are potential candidates to develop practical oxygen
      sensors. 

PMID- 24564768
TI  - Angiotensin-converting enzyme 2 is subject to post-transcriptional regulation by
      miR-421.
AB  - ACE2 (angiotensin converting enzyme 2) plays a critical role in the local tissue
      RAS (renin-angiotensin system) by hydrolysing the potent hypertensive and
      mitogenic peptide AngII (angiotensin II). Changes in the levels of ACE2 have been
      observed in a number of pathologies, including cardiovascular disease, but little
      is known of the mechanisms regulating its expression. In the present study,
      therefore, the potential role of miRNAs in the regulation of ACE2 expression in
      primary human cardiac myofibroblasts was examined. Putative miRNA-binding sites
      were identified in the 3'-UTR of the ACE2 transcript using online prediction
      algorithms. Two of these, miR-200b and miR-421, were selected for further
      analysis. A reporter system using the 3'-UTR of ACE2 fused to the coding region
      of firefly luciferase was used to determine the functionality of the identified
      binding sites in vitro. This identified miR-421, but not miR-200b, as a potential
      regulator of ACE2. The ability of miR-421, an miRNA implicated in the development
      of thrombosis, to down-regulate ACE2 expression was subsequently confirmed by
      Western blot analysis of both primary cardiac myofibroblasts and transformed
      cells transfected with a synthetic miR-421 precursor. Real-time PCR analysis of
      miR-421 revealed widespread expression in human tissues. miR-421 levels in
      cardiac myofibroblasts showed significant inter-patient variability, in keeping
      with the variability of ACE2 expression we have observed previously. In
      conclusion, the present study is the first to demonstrate that ACE2 may be
      subject to post-transcriptional regulation and reveals a novel potential
      therapeutic target, miR-421, which could be exploited to modulate ACE2 expression
      in disease. 

PMID- 24564769
TI  - CD11b+ DCs rediscovered: implications for vaccination.
AB  - Dendritic cells (DCs) are potent antigen sensing and presenting cells, able to
      both initiate and orchestrate complex immune responses. DCs are optimally
      equipped to recognize pathogens, as well as self-antigens and vaccine components,
      and instruct the type, magnitude and specificity of the ensuing immunity.
      However, the DC population is remarkably heterogeneous and consists of multiple
      subsets with different ontogeny, differentiation and functional specializations.
      Therefore, a deeper understanding of DC subset biology is fundamental for the
      development and implementation of innovative vaccination strategies. 

PMID- 24564771
TI  - Combined experimental and computational investigations of rhodium- and ruthenium
      catalyzed C-H functionalization of pyrazoles with alkynes.
AB  - Detailed experimental and computational studies are reported on the mechanism of
      the coupling of alkynes with 3-arylpyrazoles at [Rh(MeCN)3Cp*][PF6]2 and [RuCl2(p
      cymene)]2 catalysts. Density functional theory (DFT) calculations indicate a
      mechanism involving sequential N-H and C-H bond activation, HOAc/alkyne exchange,
      migratory insertion, and C-N reductive coupling. For rhodium, C-H bond activation
      is a two-step process comprising kappa(2)-kappa(1) displacement of acetate to
      give an agostic intermediate which then undergoes C-H bond cleavage via proton
      transfer to acetate. For the reaction of 3-phenyl-5-methylpyrazole with 4-octyne
      k(H)/k(D) = 2.7 +/- 0.5 indicating that C-H bond cleavage is rate limiting in
      this case. However, H/D exchange studies, both with and without added alkyne,
      suggest that the migratory insertion transition state is close in energy to that
      for C-H bond cleavage. In order to model this result correctly, the DFT
      calculations must employ the full experimental system and include a treatment of
      dispersion effects. A significantly higher overall barrier to catalysis is
      computed at {Ru(p-cymene)} for which the rate-limiting process remains C-H
      activation. However, this is now a one-step process corresponding to the kappa(2)
      kappa(1) displacement of acetate and so is still consistent with the lack of a
      significant experimental isotope effect (k(H)/k(D) = 1.1 +/- 0.2).

PMID- 24564770
TI  - Time to initiation of breastfeeding and neonatal mortality and morbidity: a
      systematic review.
AB  - BACKGROUND: Early breastfeeding is defined as the initiation of breastfeeding
      within twenty four hours of birth. While the benefits of breastfeeding have been
      known for decades, only recently has the role of time to initiation of
      breastfeeding in neonatal mortality and morbidity been assessed. OBJECTIVE: To
      review the evidence for early breastfeeding initiation practices and to estimate
      the association between timing and neonatal outcomes. METHODS: We systematically
      reviewed multiple databases from 1963 to 2011. Standardized abstraction tables
      were used and quality was assessed for each study utilizing the Grading of
      Recommendations Assessment, Development and Evaluation (GRADE) methodology. Three
      meta-analyses were conducted for mortality among babies surviving to 48 hours.
      RESULTS: We identified 18 studies reporting a direct association between early
      breastfeeding initiation and neonatal mortality and morbidity outcomes. The
      results of random effects analyses of data from 3 studies (from 5 publications)
      demonstrated lower risks of all-cause neonatal mortality among all live births
      (RR = 0.56 [95% CI: 0.40 - 0.79]) and among low birth weight babies (RR=0.58 [95%
      CI: 0.43 - 0.78]), and infection-related neonatal mortality (RR = 0.55 [95% CI:
      0.36 - 0.84]). Among exclusively breastfed infants, all-cause mortality risk did
      not differ between early and late initiators (RR = 0.69 [95% CI: 0.27 - 1.75]).
      CONCLUSIONS: This review demonstrates that early breastfeeding initiation is a
      simple intervention that has the potential to significantly improve neonatal
      outcomes and should be universally recommended. Significant gaps in knowledge are
      highlighted, revealing a need to prioritize additional high quality studies that
      further clarify the specific cause of death, as well as providing improved
      understanding of the independent or combined effects of early initiation and
      breastfeeding patterns.

PMID- 24564772
TI  - Use of gel electrophoresis and Raman spectroscopy to characterize the effect of
      the electronic structure of single-walled carbon nanotubes on cellular uptake.
AB  - It is well-known that the uptake of single-walled carbon nanotubes (SWNTs) by
      living cells depends on factors such as SWNT length and surface chemistry.
      Surprisingly, little is known about whether the electronic structure of a SWNT
      influences uptake. One reason for this has been the lack of methods to measure
      the uptake of SWNTs by cell populations. Previously, we developed a rapid,
      sensitive, and label-free sodium dodecyl sulfate (SDS)-polyacrylamide gel
      electrophoresis (PAGE) method for measuring the amount of SWNTs in lysates
      prepared from cultured cells ( Wang et al. Anal. Chem. 2009 , 81 , 2944 ).
      Herein, we describe the use of SDS-PAGE and microprobe Raman spectroscopy to
      detect and distinguish the electronic structure of SWNTs internalized by
      mammalian cells. Using normal rat kidney (NRK) cells and SWNTs dispersed with
      bovine serum albumin (BSA), we demonstrate that the method can detect both
      metallic and semiconducting SWNTs in lysates of cells that had internalized BSA
      SWNTs and that the uptake of BSA-SWNTs by NRK cells is not influenced by SWNT
      electronic structure. 

PMID- 24564773
TI  - [Familiar Mediterranean fever in Czech Republic].
AB  - Familiar Mediterranean fever (FMF) is a well defined autosomal recessive disease
      occurring mostly in Mediterranean regions. Here we present the experience from
      one center from Czech Republic, where we follow 4 families with patients with
      genetically proven FMF. Three out of these 4 families cluster to one limited
      region in Moravia, in the heart of Europe, without any linkage to Mediterranean
      origin. Furthermore, majority of these patients are heterozygots presenting with
      well defined typical clinical symptoms. Potential pseudodominant inheritance
      and/or epigenetic and environmental factors might influence clinical presentation
      of the disease.

PMID- 24564774
TI  - [Familial Mediterranean fever - clinical picture, diagnosis and treatment].
AB  - Familial mediterranean fever (FMF) is the most prevalent genetically determined
      autoinflammatory disease. FMF significantly decreases the quality of life and
      limits life expectancy due to the development of amyloidosis in affected
      individuals. Prevalence of FMF is highest in the south-eastern Mediterraneans. In
      other parts of the world, its occurance is often restricted to high-risk ethnic
      goups. In Central Europe, experience with FMF is scarse. As for Slovakia, we have
      reported the first cases of FMF in ethnic Slovaks only recently. Along with their
      complicated fates, this has lead us to compile a comprehensive overview of the
      clinical picture, diagnosis and treatment of this elusive disease. Hereby we hope
      to be able to promote the awareness about this disease and possibly aid the
      diagnosis in new patients.

PMID- 24564775
TI  - [Food intake regulation - 2nd part].
AB  - The review article summarizes the principles of hedonic regulation of food intake
      which represents the food intake independent on the maintenance of homeostasis.
      The theory describing hedonic regulation, so called Incentive Salience Theory,
      comprises three major processes: liking (positive attribution to food stimulus),
      wanting (motivation to gain it) and learning (identification of these stimuli and
      distinguishing them from those connected with aversive reaction). Neuronal reward
      circuits are the anatomical and functional substrates of hedonic regulation. They
      react to gustatory and olfactory (or visual) stimuli associated with food intake.
      A food item is preferred in case its consumption is connected with a pleasant
      feeling thus promoting the behavioural reaction. The probability of this reaction
      after repetitive exposure to such a stimulus is increased (learned preference).
      On the contrary, learned aversion after repetitive exposure is connected with
      avoidance of a food item associated with a negative feeling. Main mediators of
      hedonic regulation are endocannabinoids, opioids and monoamines (dopamine,
      serotonin). Dopamine in dorsal striatum via D2 receptors generates food
      motivation as a key means of survival, however in ventral striatum (nucleus
      accumbens) is responsible for motivation to food bringing pleasure. Serotonin via
      its receptors 5-HT1A a T-HT2C decreases intake of palatable food. It plays a
      significant role in the pathogenesis of eating disorders, particularly mental
      anorexia. There, a food restriction represents a kind of automedication to
      constitutionally pathologically increased serotonin levels. Detailed
      understanding of processes regulating food intake is a key to new pharmacological
      interventions in eating disorders.

PMID- 24564776
TI  - [Vitamin D in relation to head and neck cancer].
AB  - Vitamin D was lately introduced as the important anti-cancer agent with
      therapeutic potential to be used in prevention and therapy of malignant tumors.
      Head and neck squamous cell cancer (HNSCC) is the sixth most common cancer in the
      world. Prognosis of this cancer is in most patients poor. In attempts to improve
      therapy of this cancer, contemporary research is focused on extension of the
      etiological and pathobiological aspects of cancerogenesis of HNSCC. This fact
      provoked us to summarize present scientific knowledge about etiopathological,
      chemopreventive and therapeutic role of vitamin D in head and neck squamous
      cancer and outline the direction of further research in this interesting and from
      clinical point of view important field. Key words: head and neck squamous cell
      carcinoma - anti-tumor effect - vitamin D. 

PMID- 24564777
TI  - [International guidelines for management of severe sepsis and septic shock 2012 -
      comment].
AB  - Sepsis is one of the leading and grossly under recognized cause of death in the
      world. If not recognized early and treated promptly, sepsis leads to septic
      shock, multiorgan failure and death. This article summarizes recently updated
      international guidelines for management of severe sepsis and septic shock.

PMID- 24564778
TI  - [The emerging pathogenesis-based strategies for treating sepsis].
AB  - The cornerstones of therapy for sepsis and septic shock remain the prompt and
      adequate hemodynamic resuscitation, administration of antibiotics that target the
      pathogen, removal or drainage of an infected source and organ support. Despite
      adequate treatment and advanced life-support, the mortality remains high.
      However, the development of adjunctive anti-sepsis therapies has been
      challenging, with more than 30 unsuccessful drug trials. Fortunately, recent
      advances in our understanding of the sepsis pathophysiology revealed new
      pathogenic paradigms, and, thus, provided new exciting therapeutic concepts. In
      this review, we briefly discuss emerging pathogenesis-based strategies for
      treating severe sepsis and septic shock.

PMID- 24564779
TI  - [Effect of alcohol consumption on cardiac electrophysiology].
AB  - Potentially arrhythmogenic changes of the cardiac electrical properties induced
      by the alcohol consumption may be based both on the direct action of ethanol and
      its metabolites, acetaldehyde and acetate, on cardiac ionic channels and
      carriers, and on the indirect effect mediated namely by the released
      catecholamines, pH changes or electrolyte imbalance. Abnormalities in the cardiac
      function and structure may individually contribute as well. Owing to the
      deficient information and complexity of the concurrent factors, the concrete
      arrhythmogenic mechanism remains unclear. This review shows a comprehensive view
      on the current knowledge in the arrhythmias observed in relation to the alcohol
      consumption and in changes of electrical properties of the cardiac tissue under
      the effect of ethanol and its metabolites. Possible factors contributing to the
      genesis of arrhythmias related to the alcohol consumption are briefly discussed.

PMID- 24564780
TI  - [Familial Mediterranean fever - first experiences in Slovakia].
AB  - Familial Mediterranean fever (FMF) is the most prevalent genetically determined
      autoinflammatory disease. FMF significantly decreases the quality of life and
      limits life expectancy due to the development of amyloidosis in affected
      individuals. Prevalence of FMF is highest in the south-eastern Mediterraneans. In
      other parts of the world, its occurance is often restricted to high-risk ethnic
      groups. In Central Europe, experience with FMF is scarse to none, as in the case
      of Slovakia, where no cases have been reported, so far. Herein we report the
      first five patients (3 adults and 2 children, 4 native Slovaks) in whom the
      diagnosis of FMF could be confirmed in Slovakia. Our experience demonstrates that
      FMF does occur in low-risk populations in Central Europe. Due to low prevalence
      and lack of experience, FMF diagnosis may be significantly delayed (4.5-30 years)
      and undiagnosed cases are to be expected in our population.

PMID- 24564781
TI  - Electronic conductivity of films of electroflocculated 2 nm iridium oxide
      nanoparticles.
AB  - The electronic conductivity of films of iridium oxide (IrO(x)) composed of ca. 2
      nm nanoparticles (NPs) is strongly dependent on the film oxidation state. The
      Ir(IV)O(x) NPs can be electrochemically converted to several oxidation states,
      ranging from Ir(III) to Ir(V) oxides. The NP films exhibit a very high apparent
      conductivity, e.g., 10(-2) S cm(-1), when the NPs are in the oxidized +4/+5
      state. When the film is fully reduced to its Ir(III) state, the apparent
      conductivity falls to 10(-6) S cm(-1).

PMID- 24564782
TI  - Control of the morphology of lipid layers by substrate surface chemistry.
AB  - In this study, surface coatings were used to control the morphology of the
      deposited lipid layers during vesicle spreading, i.e., to control if liposomes
      self-assemble on a surface into a supported lipid bilayer or a supported
      vesicular layer. The influence of the properties of the surface coating on
      formation of the deposited lipid layer was studied with quartz crystal
      microbalance and two-wavelength multiparametric surface plasmon resonance
      techniques. Control of lipid self-assembly on the surface was achieved by two
      different types of soft substrate materials, i.e., dextran and thiolated
      polyethylene glycol, functionalized with hydrophobic linkers for capturing the
      lipid layer. The low-molecular-weight dextran-based surface promoted formation of
      supported lipid bilayers, while the thiolated polyethylene glycol-based surface
      promoted supported vesicular layer formation. A silicon dioxide surface was used
      as a reference surface in both measurement techniques. In addition to promoting
      supported lipid bilayer formation of known lipid mixtures, the dextran surface
      also promoted supported lipid bilayer formation of vesicles containing the cell
      membrane extract of human hepatoblastoma cells. The new dextran-based surface was
      also capable of protecting the supported lipid bilayer against dehydration when
      exposed to a constant flow of air. The well-established quartz crystal
      microbalance technique was effective in determining the morphology of the formed
      lipid layer, while the two-wavelength surface plasmon resonance analysis enabled
      further complementary characterization of the adsorbed supported lipid bilayers
      and supported vesicular layers. 

PMID- 24564783
TI  - The Public's views of mental health in pregnant and postpartum women: a
      population-based study.
AB  - BACKGROUND: We used population-based data to determine the public's views of
      prenatal and postnatal mental health and to identify predictors of those views.
      METHODS: A computer-assisted telephone survey was conducted by the Population
      Health Laboratory (University of Alberta) with a random sample of participants
      from the province of Alberta, Canada. Respondents were eligible to participate if
      they were: 1) >=18 years; and 2) contacted by direct dialing. Questions were
      drawn from the Perinatal Depression Monitor, an Australian population-based
      survey on perinatal mental health; additional questions were developed and tested
      to reflect the Canadian context. Descriptive and multivariable regression
      analyses were conducted. RESULTS: Among the 1207 respondents, 74.7% had post
      secondary education, 16.3% were in childbearing years, and over half (57.4%)
      reported knowing a woman who had experienced postpartum depression. Significantly
      more respondents had high levels of knowledge of postnatal (87.4%) than prenatal
      (70.5%) mental health (p < .01). Only 26.6% of respondents accurately identified
      that prenatal anxiety/depression could negatively impact child development.
      Personal knowledge of a woman with postpartum depression was a significant
      predictor of prenatal and postnatal mental health knowledge. CONCLUSIONS: While
      the public's knowledge of postnatal mental health is high, knowledge regarding
      prenatal mental health and its influence on child development is limited.
      Strategies for improving perinatal mental health literacy should target these
      knowledge deficits.

PMID- 24564784
TI  - A comprehensive genetic map of sugarcane that provides enhanced map coverage and
      integrates high-throughput Diversity Array Technology (DArT) markers.
AB  - BACKGROUND: Sugarcane genetic mapping has lagged behind other crops due to its
      complex autopolyploid genome structure. Modern sugarcane cultivars have from 110
      120 chromosomes and are in general interspecific hybrids between two species with
      different basic chromosome numbers: Saccharum officinarum (2n = 80) with a basic
      chromosome number of 10 and S. spontaneum (2n = 40-128) with a basic chromosome
      number of 8. The first maps that were constructed utilised the single dose (SD)
      markers generated using RFLP, more recent maps generated using AFLP and SSRs
      provided at most 60% genome coverage. Diversity Array Technology (DArT) markers
      are high throughput allowing greater numbers of markers to be generated. RESULTS:
      Progeny from a cross between a sugarcane variety Q165 and a S. officinarum
      accession IJ76-514 were used to generate 2467 SD markers. A genetic map of Q165
      was generated containing 2267 markers, These markers formed 160 linkage groups
      (LGs) of which 147 could be placed using allelic information into the eight basic
      homology groups (HGs) of sugarcane. The HGs contained from 13 to 23 LGs and from
      204 to 475 markers with a total map length of 9774.4 cM and an average density of
      one marker every 4.3 cM. Each homology group contained on average 280 markers of
      which 43% were DArT markers 31% AFLP, 16% SSRs and 6% SNP markers. The multi
      allelic SSR and SNP markers were used to place the LGs into HGs. CONCLUSIONS: The
      DArT array has allowed us to generate and map a larger number of markers than
      ever before and consequently to map a larger portion of the sugarcane genome.
      This larger number of markers has enabled 92% of the LGs to be placed into the 8
      HGs that represent the basic chromosome number of the ancestral species, S.
      spontaneum. There were two HGs (HG2 and 8) that contained larger numbers of LGs
      verifying the alignment of two sets of S. officinarum chromosomes with one set of
      S. spontaneum chromosomes and explaining the difference in basic chromosome
      number between the two ancestral species. There was also evidence of more complex
      structural differences between the two ancestral species.

PMID- 24564785
TI  - Redox centers evolution in phospho-olivine type (LiFe0.5Mn0.5 PO4) nanoplatelets
      with uniform cation distribution.
AB  - In phospho-olivine type structures with mixed cations (LiM1M2PO4), the octahedral
      M1 and M2 sites that dictate the degree of intersites order/disorder play a key
      role in determining their electrochemical redox potentials. In the case of
      LiFexMn1-xPO4, for example, in micrometer-sized particles synthesized via
      hydrothermal route, two separate redox centers corresponding to Fe(2+)/Fe(3+)
      (3.5 V vs Li/Li(+)) and Mn(2+)/Mn(3+) (4.1 V vs Li/Li(+)), due to the collective
      Mn-O-Fe interactions in the olivine lattice, are commonly observed in the
      electrochemical measurements. These two redox processes are directly reflected as
      two distinct peak potentials in cyclic voltammetry (CV) and equivalently as two
      voltage plateaus in their standard charge/discharge characteristics (in Li ion
      batteries). On the contrary, we observed a single broad peak in CV from
      LiFe0.5Mn0.5PO4 platelet-shaped (~10 nm thick) nanocrystals that we are reporting
      in this work. Structural and compositional analysis showed that in these
      nanoplatelets the cations (Fe, Mn) are rather homogeneously distributed in the
      lattice, which is apparently the reason for a synergetic effect on the redox
      potentials, in contrast to LiFe0.5Mn0.5PO4 samples obtained via hydrothermal
      routes. After a typical carbon-coating process in a reducing atmosphere (Ar/H2),
      these LiFe0.5Mn0.5PO4 nanoplatelets undergo a rearrangement of their cations into
      Mn-rich and Fe-rich domains. Only after such cation rearrangement (via
      segregation) in the nanocrystals, the redox processes evolved at two distinct
      potentials, corresponding to the standard Fe(2+)/Fe(3+) and Mn(2+)/Mn(3+) redox
      centers. Our experimental findings provide new insight into mixed-cation olivine
      structures in which the degree of cations mixing in the olivine lattice directly
      influences the redox potentials, which in turn determine their charge/discharge
      characteristics. 

PMID- 24564786
TI  - Fungal plant cell wall-degrading enzyme database: a platform for comparative and
      evolutionary genomics in fungi and Oomycetes.
AB  - BACKGROUND: Plant cell wall-degrading enzymes (PCWDEs) play significant roles
      throughout the fungal life including acquisition of nutrients and decomposition
      of plant cell walls. In addition, many of PCWDEs are also utilized by biofuel and
      pulp industries. In order to develop a comparative genomics platform focused in
      fungal PCWDEs and provide a resource for evolutionary studies, Fungal PCWDE
      Database (FPDB) is constructed (http://pcwde.riceblast.snu.ac.kr/). RESULTS: In
      order to archive fungal PCWDEs, 22 sequence profiles were constructed and
      searched on 328 genomes of fungi, Oomycetes, plants and animals. A total of 6,682
      putative genes encoding PCWDEs were predicted, showing differential distribution
      by their life styles, host ranges and taxonomy. Genes known to be involved in
      fungal pathogenicity, including polygalacturonase (PG) and pectin lyase, were
      enriched in plant pathogens. Furthermore, crop pathogens had more PCWDEs than
      those of rot fungi, implying that the PCWDEs analysed in this study are more
      needed for invading plant hosts than wood-decaying processes. Evolutionary
      analysis of PGs in 34 selected genomes revealed that gene duplication and loss
      events were mainly driven by taxonomic divergence and partly contributed by those
      events in species-level, especially in plant pathogens. CONCLUSIONS: The FPDB
      would provide a fungi-specialized genomics platform, a resource for evolutionary
      studies of PCWDE gene families and extended analysis option by implementing
      Favorite, which is a data exchange and analysis hub built in Comparative Fungal
      Genomics Platform (CFGP 2.0; http://cfgp.snu.ac.kr/).

PMID- 24564787
TI  - Lack of association between the IL-13 C-1112T, G2044A polymorphisms and Graves'
      disease risk: evidence from a meta-analysis.
AB  - BACKGROUND: Previous studies have provided conflicting evidence implicating the
      IL-13 C-1112T and G2044A polymorphisms in Graves' disease (GD) risk. We undertook
      a meta-analysis to address this issue. METHODS: The Medline, Pubmed and Web of
      Science databases were searched for published case-control studies investigating
      the relation of the IL-13 C-1112T and G2044A polymorphisms with GD risk. Data
      were extracted using standardized forms and odds ratios (OR) with 95% confidence
      intervals (CI) were calculated. RESULTS: Available data did not suggest an
      association between any of the two IL-13 polymorphisms and GD risk. For the C
      1112T polymorphism, the combined OR was 0.96 (95% CI: 0.77-1.19) for dominant
      model (TT+CT vs CC), 0.97 (95% CI: 0.69-1.38) for recessive model (TT vs CT+CC),
      and 0.97 (95% CI: 0.68-1.39) for homozygote model (TT vs CC). ORs for the G2044A
      polymorphism were similar. In subgroup analyses stratified by ethnicity, we also
      did not find associations between these two variants and GD risk in Asians or
      Caucasians. Sensitivity analyses by excluding each of the involved study in turn
      did not change the pooled results. CONCLUSION: The IL-13 C-1112T and G2044A
      polymorphisms are not associated with GD risk.

PMID- 24564788
TI  - Fibril formation from pea protein and subsequent gel formation.
AB  - The objective of this study was to characterize fibrillar aggregates made using
      pea proteins, to assemble formed fibrils into protein-based gels, and to study
      the rheological behavior of these gels. Micrometer-long fibrillar aggregates were
      observed after pea protein solutions had been heated for 20 h at pH 2.0.
      Following heating of pea proteins, it was observed that all of the proteins were
      hydrolyzed into peptides and that 50% of these peptides were assembled into
      fibrils. Changes on a structural level in pea proteins were studied using
      circular dichroism, transmission electron microscopy, and particle size analysis.
      During the fibril assembly process, an increase in aggregate size was observed,
      which coincided with an increase in thioflavin T binding, indicating the presence
      of beta-sheet aggregates. Fibrils made using pea proteins were more branched and
      curly. Gel formation of preformed fibrils was induced by slow acidification from
      pH 7.0 to a final pH of around pH 5.0. The ability of pea protein-based fibrillar
      gels to fracture during an amplitude sweep was comparable to those of soy protein
      and whey protein-based fibrillar gels, although gels prepared from fibrils made
      using pea protein and soy protein were weaker than those of whey protein. The
      findings show that fibrils can be prepared from pea protein, which can be
      incorporated into protein-based fibrillar gels.

PMID- 24564789
TI  - Protein folding in HP model on hexagonal lattices with diagonals.
AB  - Three dimensional structure prediction of a protein from its amino acid sequence,
      known as protein folding, is one of the most studied computational problem in
      bioinformatics and computational biology. Since, this is a hard problem, a number
      of simplified models have been proposed in literature to capture the essential
      properties of this problem. In this paper we introduce the hexagonal lattices
      with diagonals to handle the protein folding problem considering the well
      researched HP model. We give two approximation algorithms for protein folding on
      this lattice. Our first algorithm is a 5/3-approximation algorithm, which is
      based on the strategy of partitioning the entire protein sequence into two
      pieces. Our next algorithm is also based on partitioning approaches and improves
      upon the first algorithm.

PMID- 24564790
TI  - Engineering interaction between bone marrow derived endothelial cells and
      electrospun surfaces for artificial vascular graft applications.
AB  - The aim of this investigation was to understand and engineer the interactions
      between endothelial cells and the electrospun (ES) polyvinylidene fluoride-co
      hexafluoropropylene (PVDF-HFP) nanofiber surfaces and evaluate their potential
      for endothelialization. Elastomeric PVDF-HFP samples were electrospun to evaluate
      their potential use as small diameter artificial vascular graft scaffold (SDAVG)
      and compared with solvent cast (SC) PVDF-HFP films. We examined the consequences
      of fibrinogen adsorption onto the ES and SC samples for endothelialisation. Bone
      marrow derived endothelial cells (BMEC) of human origin were incubated with the
      test and control samples and their attachment, proliferation, and viability were
      examined. The nature of interaction of fibrinogen with SC and ES samples was
      investigated in detail using ELISA, XPS, and FTIR techniques. The pristine SC and
      ES PVDF-HFP samples displayed hydrophobic and ultrahydrophobic behavior and
      accordingly, exhibited minimal BMEC growth. Fibrinogen adsorbed SC samples did
      not significantly enhance endothelial cell binding or proliferation. In contrast,
      the fibrinogen adsorbed electrospun surfaces showed a clear ability to modulate
      endothelial cell behavior. This system also represents an ideal model system that
      enables us to understand the natural interaction between cells and their
      extracellular environment. The research reported shows potential of ES surfaces
      for artificial vascular graft applications. 

PMID- 24564791
TI  - QTREDS: a Ruby on Rails-based platform for omics laboratories.
AB  - BACKGROUND: In recent years, the experimental aspects of the laboratory
      activities have been growing in complexity in terms of amount and diversity of
      data produced, equipment used, of computer-based workflows needed to process and
      analyze the raw data generated. To enhance the level of quality control over the
      laboratory activities and efficiently handle the large amounts of data produced,
      a Laboratory Management Information System (LIMS) is highly-recommended. A LIMS
      is a complex software platform that helps researchers to have a complete
      knowledge of the laboratory activities at each step encouraging them to adopt
      good laboratory practices. RESULTS: We have designed and implemented Quality and
      TRacEability Data System--QTREDS, a software platform born to address the
      specific needs of the CRS4 Sequencing and Genotyping Platform (CSGP). The system
      written in the Ruby programming language and developed using the Rails framework
      is based on four main functional blocks: a sample handler, a workflow generator,
      an inventory management system and a user management system. The wizard-based
      sample handler allows to manage one or multiple samples at a time, tracking the
      path of each sample and providing a full chain of custody. The workflow generator
      encapsulates a user-friendly JavaScript-based visual tool that allows users to
      design customized workflows even for those without a technical background. With
      the inventory management system, reagents, laboratory glassware and consumables
      can be easily added through their barcodes and minimum stock levels can be
      controlled to avoid shortages of essential laboratory supplies. QTREDS provides a
      system for privileges management and authorizations to create different user
      roles, each with a well-defined access profile. CONCLUSIONS: Tracking and
      monitoring all the phases of the laboratory activities can help to identify and
      troubleshoot problems more quickly, reducing the risk of process failures and
      their related costs. QTREDS was designed to address the specific needs of the
      CSGP laboratory, where it has been successfully used for over a year, but thanks
      to its flexibility it can be easily adapted to other "omics" laboratories. The
      software is freely available for academic users from http://qtreds.crs4.it.

PMID- 24564792
TI  - Transient receptor potential melastatin (TRPM) channels mediate clozapine-induced
      phenotypes in Caenorhabditis elegans.
AB  - The molecular mechanisms of action of antipsychotic drugs (APDs) are not fully
      understood. Here, we characterize phenotypes of missense and knockout mutations
      in the Caenorhabditis elegans transient receptor potential melastatin (TRPM)
      channel ortholog gtl-2, a candidate APD target identified in a genome-wide RNAi
      (RNA interference) screen for Suppressors of Clozapine-induced Larval Arrest
      (scla genes). We then employ the developmental phenotypes of gtl-2(lf) mutants to
      validate our previous gtl-2(RNAi) result. GTL-2 acts in the excretory canal cell
      to regulate Mg(2+) homeostasis. Using exc (excretory canal abnormal) gene
      mutants, we demonstrate that excretory canal cell function is necessary for
      clozapine-induced developmental delay and lethality. Moreover, cell-specific
      promoter-driven expression studies reveal that GTL-2 function in the excretory
      canal cell is important for its role in the SCLA phenotype. We then investigate
      the mechanism by which GTL-2 function in the excretory canal cell impacts
      clozapine-induced phenotypes. gtl-2(lf) mutations cause hypermagnesemia, and we
      show that exposure of the wild-type strain to high Mg(2+) phenocopies gtl-2(lf)
      with respect to suppression of clozapine-induced developmental delay and
      lethality. Our results suggest that GTL-2 TRPM channel function in the excretory
      canal cell is important for clozapine's developmental effects. TRP channels are
      expressed in mammalian brain and are implicated in the pathogenesis of mental
      illnesses but have not been previously implicated in APD action.

PMID- 24564793
TI  - Obesity and body size perceptions in a Spanish Roma population.
AB  - BACKGROUND: Roma people are particularly vulnerable to developing overweight and
      obesity. Self-perception of body image may influence the prevalence of obesity in
      this ethnic minority. AIM: The objectives of this study are to estimate the
      prevalence of obesity, to analyse body size perceptions and preferences and to
      assess the relationship between body size perceptions and obesity in the Roma
      population. SUBJECTS AND METHODS: The analyses were carried out on 372 men, women
      and children from the Roma population residing in the Greater Bilbao region
      (Basque Country, Spain). In adults, a standard figural scale was used to analyse
      body size perceptions and preferences in this ethnic minority. RESULTS: Overall
      51.7% of adult and 24.4% of minor Roma individuals were obese. Both Roma men and
      women had inaccurate self-perceptions of their body size. Significant differences
      on body size perceptions were detected based on age, sex, nutritional status and
      socioeconomic characteristics. CONCLUSION: This Roma population presents one of
      the highest rates of obesity worldwide. Although a certain awareness of the
      correct weight status was appreciated, the inability of Roma individuals to see
      themselves as overweight or obese may be a significant factor on the high
      prevalence of obesity in this population.

PMID- 24564794
TI  - Agent based modeling of Treg-Teff cross regulation in relapsing-remitting
      multiple sclerosis.
AB  - BACKGROUND: Multiple sclerosis (MS) is a disease of central nervous system that
      causes the removal of fatty myelin sheath from axons of the brain and spinal
      cord. Autoimmunity plays an important role in this pathology outcome and body's
      own immune system attacks on the myelin sheath causing the damage. The etiology
      of the disease is partially understood and the response to treatment cannot
      easily be predicted. RESULTS: We presented the results obtained using 8
      genetically predisposed randomly chosen individuals reproducing both the absence
      and presence of malfunctions of the Teff-Treg cross-balancing mechanisms at a
      local level. For simulating the absence of a local malfunction we supposed that
      both Teff and Treg populations had similar maximum duplication rates. Results
      presented here suggest that presence of a genetic predisposition is not always a
      sufficient condition for developing the disease. Other conditions such as a
      breakdown of the mechanisms that regulate and allow peripheral tolerance should
      be involved. CONCLUSIONS: The presented model allows to capture the essential
      dynamics of relapsing-remitting MS despite its simplicity. It gave useful
      insights that support the hypothesis of a breakdown of Teff-Treg cross balancing
      mechanisms.

PMID- 24564796
TI  - The antibacterial and anti-biofouling performance of biogenic silver
      nanoparticles by Lactobacillus fermentum.
AB  - Biofouling is a major challenge in the water industry and public health. Silver
      nanoparticles (AgNPs) have excellent antimicrobial properties and are considered
      to be a promising anti-biofouling agent. A modified method was used to produce
      small sized and well-dispersed biogenic silver nanoparticles with a mean size of
      ~6 nm (Bio-Ag0-6) using Lactobacillus fermentum. The morphology, size
      distribution, zeta potential and oxidation state of the silver were
      systematically characterized. Determination of minimal inhibitory and
      bactericidal concentration results revealed that biogenic silver Bio-Ag(0-6) can
      effectively suppress the growth of the test bacteria. Additionally, the
      inhibition effects of Bio-Ag(0-6) on biofilm formation and on established
      biofilms were evaluated using P. aeruginosa (ATCC 27853) as the model bacterium.
      The results from microtiter plates and confocal laser scanning microscopy
      demonstrated that Bio-Ag(0-6) not only exhibited excellent antibacterial
      performance but also could control biofilm formation and induce detachment of the
      bulk of P. aeruginosa biofilms leaving a small residual matrix. 

PMID- 24564795
TI  - The effect of antiemetics in childhood gastroenteritis.
AB  - INTRODUCTION: Diarrheal diseases are the second leading cause of childhood
      morbidity and mortality in developing countries and an important cause of
      malnutrition. An estimated 0.75 million children below 5 years of age die from
      diarrhea. Vomiting associated with acute gastroenteritis (AGE) is a distressing
      symptom and limits the success of oral rehydration in AGE leading to an increased
      use of intravenous rehydration, prolonged emergency department stay and
      hospitalization. In this review we estimate the effect of antiemetics in
      gastroenteritis in children. METHODS: We conducted a systematic review of all the
      efficacy and effectiveness studies. We used a standardized abstraction and
      grading format and performed meta-analyses for all outcomes with more than two
      studies. The estimated effect of antiemetics was determined by applying the
      standard Child Health Epidemiology Reference Group (CHERG) rules. RESULTS: We
      included seven studies in the review. Antiemetics significantly reduced the
      incidence of vomiting and hospitalization by 54%. Antiemetics also significantly
      reduced the intravenous fluid requirements by 60%, while it had a non-significant
      effect on the ORT tolerance and revisit rates. CONCLUSION: Antiemetics are
      effective for the management of gastroenteritis in children and have the
      potential to decrease morbidity and mortality burden due to diarrhea, when
      introduced and scaled up.

PMID- 24564797
TI  - Film-coated matrix mini-tablets for the extended release of a water-soluble drug.
AB  - Extended release (ER) of water-soluble drugs from hydroxypropylmethylcellulose
      (HPMC) matrix mini-tablets (mini-matrices) is difficult to achieve due to the
      large surface area to volume ratio of the mini matrices. Therefore, the aims of
      this study were to control the release of a water-soluble drug (theophylline)
      from mini-matrices by applying ER ethylcellulose film coating (Surelease(r)), and
      to assess the effects of Surelease(r):pore former (Opadry(r)) ratio and coating
      load on release rates. Mini-matrices containing 40%w/w HPMC K100M CR were coated
      with 100:0, 85:15, 80:20, 75:25 or 70:30 Surelease(r):Opadry(r) to different
      coating weight gains (6-20%). Non-matrix mini-tablets were also produced and
      coated with 80:20 Surelease(r):Opadry(r) to different coating weight gains. At
      low coating weight gains, nonmatrix mini-tablets released the entire drug within
      0.5 h, while at high coating weight gains only a very small amount (<5%) of drug
      was released after 12 h. The gel formation of HPMC prevented disintegration of
      mini-matrices at low coating weight gains but contributed to rupture of the film
      even at high coating weight gains. As a result, drug release from mini-matrices
      was slower than that from nonmatrix mini-tablets at low coating weight gains, yet
      faster at high coating weight gains. An increase in the lag time of drug release
      from mini-matrices was observed as the concentration of Opadry(r) reduced or the
      coating weight gain increased. This study has demonstrated the possibility of
      extending the release of a water-soluble drug from HPMC mini-matrices by applying
      ER film coating with appropriate levels of pore former and coating weight gains
      to tailor the release rate. 

PMID- 24564798
TI  - Improved tumor targetability of Tat-conjugated PAMAM dendrimers as a novel
      nanosized anti-tumor drug carrier.
AB  - The generation 4-poly-amidoamine-dendrimers (PAMAM G4 dendrimer, P) was
      conjugated to Tat peptide (Tat, T), a cell-penetrating peptide, in search of an
      efficient anti-tumor drug delivery vehicle for cancer therapy. In this study, we
      synthesized BODIPY-labeled Tat-Conjugated PAMAM dendrimers (BPTs) as a novel
      nanosized anticancer drug carriers and systemically investigated their
      biodistribution and the tumor accumulation in Sarcoma 180-bearing mice. In
      addition, the uptake and the cytotoxicity to S180 cells of BPTs thereof were
      evaluated. The unmodified dendrimer (BP) showed a soon clearance from the blood
      stream and nonspecific accumulation in tumor. In contrast, the Tat-modified
      dendrimer, BPT(64) with appropriate particle size showed a better retention in
      blood and could be accumulated effectively in tumor tissue via the enhanced
      permeability and retention (EPR) effect. Moreover, BPTs with a high Tat
      modification rate was accumulated more effectively in tumor tissue. In vitro
      experiments, these BPTs displayed low cytotoxicity on S180 cells and high uptake
      to S180 cells. These findings indicate that the nanoparticulate system on the
      basis of Tat-conjugated PAMAM dendrimers is safer and effective in the
      concentration range (below 20 MUg/ml) to be used as a carrier of anti-tumor drugs
      for tumor targeting by intravenous administration. 

PMID- 24564799
TI  - Mannosylated solid lipid nanoparticles for lung-targeted delivery of Paclitaxel.
AB  - OBJECTIVE: The present study discusses paclitaxel (PTX)-loaded mannosylated-DSPE
      (Distearoyl-phosphatidyl-ethanolamine) solid lipid nanoparticles (M-SLNs) using
      mannose as a lectin receptor ligand conjugate for lung cancer targeting and to
      increase the anticancer activity of PTX against A549 lung's epithelial cancer
      cells. MATERIALS AND METHODS: The PTX-SLNs were prepared by solvent injection
      method and mannose was conjugated to the free amine group of stearylamine. The M
      SLNs obtained were characterized for their particle size, polydispersity index,
      zeta potential and morphology by transmission electron microscope. RESULTS: The M
      SLNs were spherical in shape with 254 +/- 2.3 nm average size, positive zeta
      potential (3.27 mV), 79.4 +/- 1.6 drug entrapment efficiency and showed the lower
      extent of drug release 40% over 48 h in vitro. Cytotoxicity study on A549 cell
      lines and biodistrubtion study of drug revealed that M-SLNs deliver a higher
      concentration of PTX as compared to PTX-SLNs in an alveolar cell site. DISCUSSION
      AND CONCLUSION: These results suggested that mannosylated M-SLNs are safe and
      potential vector for lung cancer targeting.

PMID- 24564801
TI  - Arsenite binding to sulfhydryl groups in the absence and presence of
      ferrihydrite: a model study.
AB  - Binding of arsenite (As(III)) to sulfhydryl groups (Sorg(-II)) plays a key role
      in As detoxification mechanisms of plants and microorganisms, As remediation
      techniques, and reduced environmental systems rich in natural organic matter.
      Here, we studied the formation of Sorg(-II)-As(III) complexes on a sulfhydryl
      model adsorbent (Ambersep GT74 resin) in the absence and presence of ferrihydrite
      as a competing mineral adsorbent under reducing conditions and tested their
      stability against oxidation in air. Adsorption of As(III) onto the resin was
      studied in the pH range 4.0-9.0. On the basis of As X-ray absorption spectroscopy
      (XAS) results, a surface complexation model describing the pH dependence of
      As(III) binding to the organic adsorbent was developed. Stability constants (log
      K) determined for dithio ((AmbS)2AsO(-)) and trithio ((AmbS)3As) surface
      complexes were 8.4 and 7.3, respectively. The ability of sulfhydryl ligands to
      compete with ferrihydrite for As(III) was tested in various anoxic mixtures of
      both adsorbents at pH 7.0. At a 1:1 ratio of their reactive binding sites, R-SH
      and =FeOH, both adsorbents possessed nearly identical affinities for As(III). The
      oxidation of Sorg(-II)-As(III) complexes in water vapor saturated air over 80
      days, monitored by As and S XAS, revealed that the complexed As(III) is
      stabilized against oxidation (t1/2 = 318 days). Our results thus document that
      sulfhydryl ligands are highly competitive As(III) complexing agents that can
      stabilize As in its reduced oxidation state even under prolonged oxidizing
      conditions. These findings are particularly relevant for organic S-rich
      semiterrestrial environments subject to periodic redox potential changes such as
      peatlands, marshes, and estuaries. 

PMID- 24564802
TI  - Surveillance of paediatric traumatic brain injuries using the NEISS: choosing an
      appropriate case definition.
AB  - OBJECTIVE: To evaluate the definition of traumatic brain injury (TBI) in the
      National Electronic Injury Surveillance System (NEISS) and compare TBI case
      ascertainment using NEISS vs. ICD-9-CM diagnosis coding. METHODS: Two data
      samples from a NEISS participating emergency department (ED) in 2008 were
      compared: (1) NEISS records meeting the recommended NEISS TBI definition and (2)
      Hospital ED records meeting the ICD-9-CM CDC recommended TBI definition. The
      sensitivity and positive predictive value were calculated for the NEISS
      definition using the ICD-9-CM definition as the gold standard. Further analyses
      were performed to describe cases characterized as TBIs in both datasets and to
      determine why some cases were not classified as TBIs in both datasets. RESULTS:
      There were 1834 TBI cases captured by the NEISS and 1836 TBI cases captured by
      the ICD-9-CM coded ED record, but only 1542 were eligible for inclusion in NEISS.
      There were 1403 cases classified as TBIs by both the NEISS and ICD-9-CM diagnosis
      codes. The NEISS TBI definition had a sensitivity of 91.0% (95% CI = 89.6-92.4%)
      and positive predictive value of 76.5% (95% CI = 74.6-78.4%). CONCLUSIONS: Using
      the NEISS TBI definition presented in this paper would standardize and improve
      the accuracy of TBI research using the NEISS.

PMID- 24564803
TI  - Enhancement of light emission from silicon by precisely tuning coupled localized
      surface plasmon resonance of a nanostructured platinum layer prepared by atomic
      layer deposition.
AB  - Plasmonic enhancement of photoluminescence from bulk silicon was achieved by
      spectrally tailoring coupled localized surface plasmon resonance (LSPR) in the
      Al2O3 cover/nanostructured platinum (nano-Pt)/Al2O3 spacer/silicon multilayer
      structures prepared by atomic layer deposition (ALD). Agreement between the
      simulation and experimental data indicates that the plasmonic activity originates
      from absorption enhancement due to coupled LSPR. Because of the optimized
      dielectric environment deposited by ALD around the nano-Pt layer, absorption of
      the multilayer structure was enhanced by the precise tuning of coupled LSPR to
      coincide with the excitation wavelength. This accurate plasmonic multilayer
      structure grown by ALD with high precision, tunability, uniformity, and
      reproducibility can be further applied in efficient light-emitting devices. 

PMID- 24564800
TI  - The associations of parity and maternal age with small-for-gestational-age,
      preterm, and neonatal and infant mortality: a meta-analysis.
AB  - BACKGROUND: Previous studies have reported on adverse neonatal outcomes
      associated with parity and maternal age. Many of these studies have relied on
      cross-sectional data, from which drawing causal inference is complex. We explore
      the associations between parity/maternal age and adverse neonatal outcomes using
      data from cohort studies conducted in low- and middle-income countries (LMIC).
      METHODS: Data from 14 cohort studies were included. Parity (nulliparous, parity 1
      2, parity >= 3) and maternal age (<18 years, 18-<35 years, >= 35 years)
      categories were matched with each other to create exposure categories, with those
      who are parity 1-2 and age 18-<35 years as the reference. Outcomes included small
      for-gestational-age (SGA), preterm, neonatal and infant mortality. Adjusted odds
      ratios (aOR) were calculated per study and meta-analyzed. RESULTS: Nulliparous,
      age <18 year women, compared with women who were parity 1-2 and age 18-<35 years
      had the highest odds of SGA (pooled adjusted OR: 1.80), preterm (pooled aOR:
      1.52), neonatal mortality (pooled aOR: 2.07), and infant mortality (pooled aOR:
      1.49). Increased odds were also noted for SGA and neonatal mortality for
      nulliparous/age 18-<35 years, preterm, neonatal, and infant mortality for parity
      >= 3/age 18-<35 years, and preterm and neonatal mortality for parity >= 3/>= 35
      years. CONCLUSIONS: Nulliparous women <18 years of age have the highest odds of
      adverse neonatal outcomes. Family planning has traditionally been the least
      successful in addressing young age as a risk factor; a renewed focus must be
      placed on finding effective interventions that delay age at first birth. Higher
      odds of adverse outcomes are also seen among parity >= 3 / age >= 35 mothers,
      suggesting that reproductive health interventions need to address the entirety of
      a woman's reproductive period. FUNDING: Funding was provided by the Bill &
      Melinda Gates Foundation (810-2054) by a grant to the US Fund for UNICEF to
      support the activities of the Child Health Epidemiology Reference Group.

PMID- 24564804
TI  - Numerical and experimental study of suspensions containing carbon blacks used as
      conductive additives in composite electrodes for lithium batteries.
AB  - Suspensions of carbon blacks and spherical carbon particles are studied
      experimentally and numerically to understand the role of the particle shape on
      the tendency to percolation. Two commercial carbon blacks and one lab-synthesized
      spherical carbon are used. The percolation thresholds in suspensions are
      experimentally determined by two complementary methods: impedance spectroscopy
      and rheology. Brownian dynamics simulations are performed to explain the
      experimental results taking into account the fractal shape of the aggregates in
      the carbon blacks. The results of Brownian dynamics simulations are in good
      agreement with the experimental results and allow one to explain the experimental
      behavior of suspensions. 

PMID- 24564805
TI  - Ambulatory clinical pharmacy specialty services: the Kaiser Permanente Colorado
      experience.

PMID- 24564806
TI  - Improving multiple sclerosis care: an analysis of the necessity for medication
      therapy management services among the patient population.

PMID- 24564807
TI  - Use of HMG-CoA reductase inhibitors in the HIV population: implications for
      individualized treatment selection.

PMID- 24564808
TI  - Implementation of a pharmacy-based adult vaccine benefit: recommendations for a
      commercial health plan benefit.
AB  - BACKGROUND: Although vaccination rates in children exceed 90% in the United
      States, adults are vaccinated at far lower rates. In order to address this issue,
      additional community immunizers are needed, and pharmacists are in an ideal
      position to fill this void. OBJECTIVES: To explore issues and barriers related to
      implementation of a pharmacy-based adult vaccine benefit and develop
      recommendations supporting a pathway for benefit expansion. METHODS: A literature
      review on the current environment surrounding pharmacy-based adult vaccinations
      and structured interviews were conducted to inform an expert panel meeting using
      a modified Delphi process (pre/post survey). The goal was to develop
      recommendations on how to improve access to adult vaccines. RESULTS: Findings
      suggest employers play a key role in requesting changes in benefit design to
      include pharmacy-based vaccinations. However, the lack of consistent
      communication between pharmacists and primary care providers remains a
      significant barrier. CONCLUSIONS: Pharmacy-based access to vaccinations improves
      patient access and benefits individuals and employers. In order to take advantage
      of this opportunity, pharmacists must be viewed within the broader context of
      preventative care, including pharmacy-based vaccinations.

PMID- 24564809
TI  - Analysis of costs to dispense prescriptions in independently owned, closed-door
      long-term care pharmacies.
AB  - BACKGROUND: The need for accurate calculation of long-term care (LTC) pharmacies'
      costs to dispense (CTD) has become more important as payers have moved toward
      reimbursement models based on pharmacies' actual acquisition cost for drug
      products and the Centers for Medicare Medicaid Services (CMS) has implemented
      requirements that LTC pharmacies must dispense prescriptions for certain branded
      drugs in 14-day-or-less quantities. OBJECTIVES: To (a) calculate the average cost
      that the typical independently owned, closed-door LTC pharmacy currently incurs
      to dispense and deliver a prescription to the resident of a client LTC facility
      and (b) estimate how CMS-mandated changes to a 14-day-or-less dispensing cycle
      would affect the typical LTC pharmacy's average CTD. METHODS: The data
      requirements and measurement model were developed by academic researchers in
      consultation with an industry advisory committee of independent LTC pharmacy
      owners. A survey instrument was constructed to collect financial and operating
      data required to calculate the CTD. Surveys were distributed via 3 dissemination
      channels to approximately 1,000 independently owned, closed-door LTC pharmacies.
      The National Community Pharmacists Association mailed surveys to their LTC
      members; 3 major national wholesalers distributed surveys to their LTC customers
      through their newsletters; and 3 LTC group purchasing organizations distributed
      the surveys to their members through emails, newsletters, mailings, and/or
      regional meetings. Each pharmacy's CTD was calculated by dividing total LTC
      dispensing-related ?costs by the total number of prescriptions dispensed.
      Dispensing-related costs included costs incurred to physically dispense and
      deliver prescriptions (e.g., dispensing pharmacists' and technicians' salaries
      and costs of medication containers) and costs incurred to support the dispensing
      function (e.g., salaries of delivery and medical records personnel). A model
      based on dispensing-related fixed, variable, and semivariable costs was developed
      to examine the impact of shorter dispensing cycles on LTC pharmacies' CTD. A
      prescription volume increase of 19% was assumed based on converting only solid
      oral branded drugs to short-cycle dispensing. RESULTS: A diverse sample of 64
      closed-door LTC pharmacies returned usable surveys. Sales from dispensing to LTC
      facilities accounted for more than 98% of total sales. Respondents indicated that
      they currently dispensed 23% of total doses in 14-day-or-less cycles and 76% in
      28-31 day cycles. Most pharmacies used automated medication packaging technology,
      heat and cold package sealers, bar code systems, sterile compounding hoods, LTC
      printers or labelers, and electronic prescribing. The median CTD was $13.54 with
      an interquartile range (25th to 75th percentiles) of $10.51 to $17.66. More than
      half of dispensing-related costs were from personnel expense, of which
      pharmacists and managers accounted for more than 40%. The results of the fixed
      and variable cost modeling suggested that converting solid oral brand-name drugs
      from 30-day to 14-day dispensing cycles would lower the median per prescription
      CTD to between $11.63 and $12.54, depending on the assumptions made about the
      effects of semivariable costs. However, this decrease in per prescription
      dispensing cost is dwarfed by an increase in total dispensing cost incurred by
      pharmacies that results from doubling the monthly volume of short-cycle
      prescriptions that must be dispensed. The result is that the typical LTC pharmacy
      in our sample incurred a CTD of $13.54 if the medication is dispensed in a 30-day
      cycle or $23.26 if the medication is dispensed in two 14-day cycles (at a cost of
      $11.63 for each cycle dispensed). CONCLUSIONS: Our results indicated a median CTD
      of $13.54 for the typical independently owned, closed-door LTC pharmacy. Moving
      to a shorter cycle would reduce pharmacies' average per-prescription CTD but
      would increase the number of prescriptions dispensed per month. Our results
      indicated that transitioning solid oral branded products to 14-day cycles would
      reduce the median CTD to a minimum of $11.63 but would increase total dispensing
      costs because each sold oral branded prescription would require twice the number
      of monthly dispensing events.

PMID- 24564810
TI  - The GRACE checklist for rating the quality of observational studies of
      comparative effectiveness: a tale of hope and caution.
AB  - BACKGROUND: While there is growing demand for information about comparative
      effectiveness (CE), there is substantial debate about whether and when
      observational studies have sufficient quality to support decision making.
      OBJECTIVE: To develop and test an item checklist that can be used to qualify
      those observational CE studies sufficiently rigorous in design and execution to
      contribute meaningfully to the evidence base for decision support. METHODS: An 11
      item checklist about data and methods (the GRACE checklist) was developed through
      literature review and consultation with experts from professional societies,
      payer groups, the private sector, and academia. Since no single gold standard
      exists for validation, checklist item responses were compared with 3 different
      types of external quality ratings (N=88 articles). The articles compared
      treatment effectiveness and/or safety of drugs, medical devices, and medical
      procedures. We validated checklist item responses 3 ways against external quality
      ratings, using published articles of observational CE or safety studies: (a)
      Systematic Review-quality assessment from a published systematic review; (b)
      Single Expert Review-quality assessment made according to the solicited "expert
      opinion" of a senior researcher; and (c) Concordant Expert Review-quality
      assessments from 2 experts for which there was concordance. Volunteers (N=113)
      from 5 continents completed 280 article assessments using the checklist. Positive
      and negative predictive values (PPV, NPV, respectively) of individual items were
      estimated to compare testers' assessments with those of experts. RESULTS: Taken
      as a whole, the scale had better NPV than PPV, for both data and methods. The
      most consistent predictor of quality relates to the validity of the primary
      outcomes measurement for the study purpose. Other consistent markers of quality
      relate to using concurrent comparators, minimizing the effects of bias by prudent
      choice of covariates, and using sensitivity analysis to test robustness of
      results. Concordance of expert opinion on the quality of the rated articles was
      52%; most checklist items performed better. CONCLUSIONS: The 11-item GRACE
      checklist provides guidance to help determine which observational studies of CE
      have used strong scientific methods and good data that are fit for purpose and
      merit consideration for decision making. The checklist contains a parsimonious
      set of elements that can be objectively assessed in published studies, and user
      testing shows that it can be successfully applied to studies of drugs, medical
      devices, and clinical and surgical interventions. Although no scoring is
      provided, study reports that rate relatively well across checklist items merit in
      depth examination to understand applicability, effect size, and likelihood of
      residual bias. The current testing and validation efforts did not achieve clear
      discrimination between studies fit for purpose and those not, but we have
      identified a critical, though remediable, limitation in our approach. Not
      specifying a specific granular decision for evaluation, or not identifying a
      single study objective in reports that included more than one, left reviewers
      with too broad an assessment challenge. We believe that future efforts will be
      more successful if reviewers are asked to focus on a specific objective or
      question. Despite the challenges encountered in this testing, an agreed upon set
      of assessment elements, checklists, or score cards is critical for the maturation
      of this field. Substantial resources will be expended on studies of real-world
      effectiveness, and if the rigor of these observational assessments cannot be
      assessed, then the impact of the studies will be suboptimal. Similarly, agreement
      on key elements of quality will ensure that budgets are appropriately directed
      toward those elements. Given the importance of this task and the lessons learned
      from these extensive efforts at validation and user testing, we are optimistic
      about the potential for improved assessments that can be used for diverse
      situations by people with a wide range of experience and training. Future testing
      would benefit by directing reviewers to address a single, granular research
      question, which would avoid problems that arose by using the checklist to
      evaluate multiple objectives, by using other types of validation test sets, and
      by employing further multivariate analysis to see if any combination or sequence
      of item responses has particularly high predictive validity.

PMID- 24564811
TI  - Barriers to mesalamine adherence in patients with inflammatory bowel disease: a
      qualitative analysis.
AB  - BACKGROUND: The causes for nonadherence to mesalamine in patients with
      inflammatory bowel disease (IBD) have been characterized using mostly indirect
      methods. Patient-reported barriers are lacking in this population. OBJECTIVE: To
      identify patient-reported barriers to mesalamine adherence through direct
      interviews. METHODS: Focus groups and one-on-one interviews were undertaken in
      adult patients with IBD. Transcripts from the focus groups and interviews were
      analyzed to identify themes and links between these themes, assisted by
      qualitative data software MaxQDA. RESULTS: Of 27 patients participating, 21 (78%)
      had ulcerative colitis, and 6 (22%) had Crohn's disease. Their self-reported
      adherence ranged from complete adherence (n = 3) to intermittent nonadherence (n
      = 24). Patients frequently indicated that they were resistant to taking
      medications for their condition. The barriers to adherence that emerged from
      interviews could be categorized under a number of themes: competing priorities,
      social stigma, refill inconvenience, costs, efficacy values, side effects, and
      pill characteristics. Efficacy values reported to influence adherence included
      doubts about efficacy, consequences of missed doses, and doubts about need for
      maintenance medication. Pill characteristics reported as barriers included pill
      size and pill frequency. Despite use of electronic prescribing, obtaining refills
      was reported as an obstacle to adherence in this cohort. Decanting of pills to
      multiple containers to increase accessibility was also reported. CONCLUSIONS:
      Patients with both ulcerative colitis and Crohn's disease report a number of
      common barriers to mesalamine adherence. Factors in medication-taking behavior
      and beliefs were reported in this study that may have implications for strategies
      to improve adherence by health care providers.

PMID- 24564812
TI  - Cost variability of suggested generic treatment alternatives under the Medicare
      Part D benefit.
AB  - BACKGROUND: The substitution of generic treatment alternatives for brand-name
      drugs is a strategy that can help lower Medicare beneficiary out-of-pocket costs.
      Beginning in 2011, Medicare beneficiaries reaching the coverage gap received a
      50% discount on the full drug cost of brand-name medications and a 7% discount on
      generic medications filled during the gap. This discount will increase until
      2020, when beneficiaries will be responsible for 25% of total drug costs during
      the coverage gap. OBJECTIVE: To examine the cost variability of brand and generic
      drugs within 4 therapeutic classes before and during the coverage gap for each
      2011 California stand-alone prescription drug plan (PDP) and prospective coverage
      gap costs in 2020 to determine the effects on beneficiary out-of-pocket drug
      costs. METHODS: Equivalent doses of brand and generic drugs in the following 4
      pharmacological classes were examined: angiotensin II receptor blockers (ARBs),
      bisphosphonates, HMG-CoA reductase inhibitors (statins), and proton pump
      inhibitors (PPIs). The full drug cost and patient copay/coinsurance amounts
      during initial coverage and the coverage gap of each drug was recorded based on
      information retrieved from the Medicare website. These drug cost data were
      recorded for 28 California PDPs. RESULTS: The highest cost difference between a
      brand medication and a Centers for Medicare Medicaid Services (CMS)-suggested
      generic treatment alternative varied between $110.53 and $195.49 at full cost and
      between $51.37 and $82.35 in the coverage gap. The lowest cost difference varied
      between $38.45 and $76.93 at full cost and between -$4.11 and $18.52 during the
      gap. CONCLUSION: Medicare beneficiaries can realize significant out-of-pocket
      cost savings for their drugs by taking CMS-suggested generic treatment
      alternatives. However, due to larger discounts on brand medications made
      available through recent changes reducing the coverage gap, the potential dollar
      savings by taking suggested generic treatment alternatives during the gap is less
      compelling and will decrease as subsidies increase.

PMID- 24564813
TI  - Lung density on high resolution computer tomography (HRCT) reflects degree of
      inflammation in smokers.
AB  - BACKGROUND: Smokers have increased cell concentration in the lower respiratory
      tract indicating a chronic inflammatory state, which in some individuals may lead
      to development of chronic obstructive pulmonary disease (COPD). Computer
      tomography (CT) imaging provides means of quantifying pulmonary structure and
      early signs of disease. We investigated whether lung density on high resolution
      CT differs between smokers and never-smokers and if this were associated to
      intensity of inflammation. METHODS: Forty smoking volunteers with normal
      pulmonary function, 40 healthy never-smokers and 40 patients with COPD of GOLD
      stage I-II, were included. Mean lung attenuation and percentage of pixels in the
      lung with attenuation between -750 and -900 HU (percentage higher density
      spectrum (%HDS)) were calculated on inspiratory CT-scans. Markers of systemic
      inflammation in blood and cell counts in bronchoalveolar lavage (BAL) fluid were
      recorded. RESULTS: Lung density expressed as %HDS was increased in smokers (44.0
      +/- 5.8%) compared to both never-smokers (38.3 +/- 5.8%) and patients with COPD
      (39.1 +/- 5.8%), (p < 0.001, for both). Females had denser lungs than males,
      which was dependent on body height. Cell concentration in BAL were correlated to
      lung density in smokers (r = 0.50, p < 0.001). CONCLUSIONS: Lung density on CT is
      associated with cell concentration in BAL in smokers and may mirror an
      inflammatory response in the lung. Gender difference in lung density is dependent
      on height. In COPD with emphysema, loss of lung tissue may counterbalance the
      expected increase in density due to inflammation. The findings may help to
      interpret high resolution CT in the context of smoking and gender and highlight
      the heterogeneity of structural changes in COPD.

PMID- 24564814
TI  - The dynamics of functional classes of plant genes in rediploidized ancient
      polyploids.
AB  - RESULTS: We measure the simultaneous dynamics of duplicate orthologous gene loss
      in rosids, in asterids, and in monocots, as influenced by biological functional
      class. This pan-angiosperm view confirms common tendencies and consistency
      through time for both ancient and more recent whole genome polyploidization
      events. CONCLUSIONS: The gene loss analysis represents an assessment of post
      polyploidization evolution, at the level of individual gene families within and
      across sister genomes. Functional analysis confirms universal trends previously
      reported for more recent plant polyploidy events: genes involved with regulation
      and responses were retained in multiple copies, while genes involved with
      metabolic and catalytic processes tended to lose copies, across all three groups
      of plants.To understand the particular evolutionary patterns of plant genomes,
      there is a need to systematically survey the fate of the subgenomes of polyploids
      fixed as whole genome duplicates, including patterns of retention of duplicate,
      triplicate, etc. genes.

PMID- 24564816
TI  - The variations in the IL1RL1 gene and susceptibility to preeclampsia.
AB  - The IL1RL1, which encodes at least three isoforms by alternative splicing, has
      been identified to be involved in the initiation and perpetuation of
      inflammation. In spite of being a main contributor of maternal and perinatal
      mortality, the mechanism responsible for the pathophysiology of preeclampsia has
      not yet been well addressed. To investigate the relationship between IL1RL1
      polymorphisms and preeclampsia risk, we identified the correlation between three
      tag SNPs (rs13017455, rs1420103 and rs17027006) in IL1RL1 with preeclampsia risk
      in a case-control study. A total of 214 cases and 208 controls were recruited to
      participate in this study. Genotypes of the three SNPs were determined with the
      use of polymerase chain reaction-restriction fragment length polymorphism assay.
      Significantly reduced preeclampsia risk was found to be associated with the CT
      genotype of rs13017455 (p = 0. 032, OR = 0. 66, 95% CI = 0.45-0.97) in
      overdominant model. Differences were particularly significant in the severe
      preeclampsia subgroup (p = 0.045, OR = 0.66, 95% CI = 0.44-0.99) and the early
      onset severe preeclampsia subgroup (p = 0.0097, OR = 0.47, 95% CI = 0.26-0.84).
      Significantly increased mild preeclampsia risk was observed associated with GG
      genotype of rs1420103 polymorphisms (p = 0.029, OR = 2.18, 95% CI = 1.09-4.34),
      while reducing late-onset severe preeclampsia susceptibility was associated with
      TT genotype of rs1420103 (p = 0.02, OR = 0.49, 95% CI = 0.26-0.92).

PMID- 24564815
TI  - Involvement of co-repressor LUH and the adapter proteins SLK1 and SLK2 in the
      regulation of abiotic stress response genes in Arabidopsis.
AB  - BACKGROUND: During abiotic stress many genes that are important for growth and
      adaptation to stress are expressed at elevated levels. However, the mechanisms
      that keep the stress responsive genes from expressing under non stress conditions
      remain elusive. Recent genetic characterization of the co-repressor
      LEUNIG_HOMOLOG (LUH) and transcriptional adaptor proteins SEUSS-LIKE1 (SLK1) and
      SLK2 have been proposed to function redundantly in diverse developmental
      processes; however their function in the abiotic stress response is unknown.
      Moreover, the molecular functions of LUH, SLK1 and SLK2 remain obscure. Here, we
      show the molecular function of LUH, SLK1 and SLK2 and the role of this complex in
      the abiotic stress response. RESULTS: The luh, slk1 and slk2 mutant plants shows
      enhanced tolerance to salt and osmotic stress conditions. SLK1 and SLK2 interact
      physically with the LUFS domain in LUH forming SLK1-LUH and SLK2-LUH co-repressor
      complexes to inhibit the transcription. LUH has repressor activity, whereas SLK1
      and SLK2 function as adaptors to recruit LUH, which in turn recruits histone
      deacetylase to the target sequences to repress transcription. The stress response
      genes RD20, MYB2 and NAC019 are expressed at elevated levels in the luh, slk1 and
      slk2 mutant plants. Furthermore, these stress response genes are associated with
      decreased nucleosome density and increased acetylation levels at H3K9 and H3K14
      in the luh, slk1 and slk2 mutant plants. CONCLUSIONS: Our results indicate that
      SLK1, SLK2 and LUH form a co-repressor complex. LUH represses by means of an
      epigenetic process involving histone modification to facilitate the condensation
      of chromatin thus preventing transcription at the target genes.

PMID- 24564818
TI  - Effects of repetitive transcranial magnetic stimulation and intensive
      occupational therapy on motor neuron excitability in poststroke hemiparetic
      patients: a neurophysiological investigation using F-wave parameters.
AB  - BACKGROUND: The combination protocol of repetitive transcranial magnetic
      stimulation (RTMS) and intensive occupational therapy (OT) improves motor
      function of the paretic upper limb in poststroke patients. However, the effect of
      RTMS/OT on motor neuron excitability remains to be investigated. The purpose of
      this study was to determine the effect of 15-day application of RTMS/OT on motor
      neuron excitability in such patients using neurophysiological studies including F
      wave parameter measurements. SUBJECTS AND METHODS: Ten poststroke patients with
      spastic upper limb hemiparesis were studied (mean age: 57.4 +/- 8.1 years, +/-
      SD). Patients were hospitalized for 15 days to receive RTMS/OT. One session of 40
      min low-frequency RTMS and two sessions of 120-min intensive OT were provided
      daily. Neurophysiological studies including F-wave parameters measurements were
      performed on the days of admission/discharge. Motor function and spasticity of
      the affected upper limb were evaluated on the same time points. RESULTS: RTMS/OT
      significantly improved motor function of the affected upper limb. RTMS/OT
      decreased the modified Ashworth scale (MAS) in the affected upper limb (p <
      0.05), but did not change F-wave frequency in either upper limb. However, both F
      mean/M ratio and F-max/M ratio significantly decreased in the affected upper limb
      (all p < 0.05). CONCLUSIONS: The 15-day protocol of LF-RTMS/OT produced
      significant reduction of motor neuron excitability. RTMS/OT can potentially
      produce significant reduction in upper limb spasticity in the affected upper
      limb, although this finding should be confirmed in a larger number of patients.

PMID- 24564817
TI  - Genetic dissection of Al tolerance QTLs in the maize genome by high density SNP
      scan.
AB  - BACKGROUND: Aluminum (Al) toxicity is an important limitation to food security in
      tropical and subtropical regions. High Al saturation on acid soils limits root
      development, reducing water and nutrient uptake. In addition to naturally
      occurring acid soils, agricultural practices may decrease soil pH, leading to
      yield losses due to Al toxicity. Elucidating the genetic and molecular mechanisms
      underlying maize Al tolerance is expected to accelerate the development of Al
      tolerant cultivars. RESULTS: Five genomic regions were significantly associated
      with Al tolerance, using 54,455 SNP markers in a recombinant inbred line
      population derived from Cateto Al237. Candidate genes co-localized with Al
      tolerance QTLs were further investigated. Near-isogenic lines (NILs) developed
      for ZmMATE2 were as Al-sensitive as the recurrent line, indicating that this
      candidate gene was not responsible for the Al tolerance QTL on chromosome 5,
      qALT5. However, ZmNrat1, a maize homolog to OsNrat1, which encodes an Al(3+)
      specific transporter previously implicated in rice Al tolerance, was mapped at
      ~40 Mbp from qALT5. We demonstrate for the first time that ZmNrat1 is
      preferentially expressed in maize root tips and is up-regulated by Al, similarly
      to OsNrat1 in rice, suggesting a role of this gene in maize Al tolerance. The
      strongest-effect QTL was mapped on chromosome 6 (qALT6), within a 0.5 Mbp region
      where three copies of the Al tolerance gene, ZmMATE1, were found in tandem
      configuration. qALT6 was shown to increase Al tolerance in maize; the qALT6-NILs
      carrying three copies of ZmMATE1 exhibited a two-fold increase in Al tolerance,
      and higher expression of ZmMATE1 compared to the Al sensitive recurrent parent.
      Interestingly, a new source of Al tolerance via ZmMATE1 was identified in a
      Brazilian elite line that showed high expression of ZmMATE1 but carries a single
      copy of ZmMATE1. CONCLUSIONS: High ZmMATE1 expression, controlled either by three
      copies of the target gene or by an unknown molecular mechanism, is responsible
      for Al tolerance mediated by qALT6. As Al tolerant alleles at qALT6 are rare in
      maize, marker-assisted introgression of this QTL is an important strategy to
      improve maize adaptation to acid soils worldwide.

PMID- 24564819
TI  - Optically active multilayer films based on chitosan and an azopolymer.
AB  - The layer-by-layer technique has been widely adopted for the fabrication of
      nanostructures with tailored properties. In this work, photoactive multilayer
      films consisting of alternating layers of chitosan and an azopolymer were
      developed by this method. Taking into account that pH is the factor controlling
      the charge of weak polyelectrolytes, the influence of this parameter on the
      structure and properties of the multilayer films was evaluated. Thus, different
      films were prepared by varying pH conditions as well as bilayer number. The
      morphology and properties of the films were analyzed by diverse advanced
      techniques, such as ultraviolet-visible spectroscopy, X-ray diffraction, and
      atomic force microscopy equipped with PeakForce QNM (Quantitative Nanomechanical
      Property Mapping). It was found that the thickness, roughness and elastic modulus
      of the developed multilayer films increased with the decrease of the chitosan
      solution pH and the increase of the bilayer number. Furthermore, induced
      birefringence measurements revealed that a higher level of photo-orientation was
      attained with the decrease of pH and the increase of bilayer number. 

PMID- 24564820
TI  - Modelling foetal growth in a bi-ethnic sample: results from the Born in Bradford
      (BiB) birth cohort.
AB  - BACKGROUND: Attempts to explain the increased risk for metabolic disorders
      observed in South Asians have focused on the "South Asian" phenotype at birth and
      subsequent post-natal growth, with little research on pre-natal growth. AIM: To
      identify whether divergent growth patterns exist for foetal weight, head (HC) and
      abdominal circumferences (AC) in a sample of Pakistani and White British
      foetuses. SUBJECTS AND METHODS: Models were based on 5553 (weight), 5154 (HC) and
      5099 (AC) foetuses from the Born in Bradford birth cohort. Fractional polynomials
      and mixed effects models were employed to determine growth patterns from ~15
      weeks of gestation-birth. RESULTS: Pakistani foetuses were significantly smaller
      and lighter as early as 20 weeks. However, there was no ethnic difference in the
      growth patterns of weight and HC. For AC, Pakistani foetuses displayed a trend
      for reduced growth in the final trimester. CONCLUSION: As the pattern of weight
      and HC growth was not significantly different during the period under
      investigation, the mechanism culminating in the reduced Pakistani size at birth
      may act earlier in gestation. Reduced AC growth in Pakistanis may represent
      reduced growth of the visceral organs, with consequences for post-natal liver
      metabolism and renal function.

PMID- 24564821
TI  - Factors influencing social and health outcomes after motor vehicle crash injury:
      an inception cohort study protocol.
AB  - BACKGROUND: There is growing evidence that health and social outcomes following
      motor vehicle crash injury are related to cognitive and emotional responses of
      the injured individual, as well as relationships between the injured individual
      and the compensation systems with which they interact. As most of this evidence
      comes from other states in Australia or overseas, investigation is therefore
      warranted to identify the key determinants of health and social outcomes
      following injury in the context of the New South Wales motor accident insurance
      scheme. METHODS/DESIGN: In this inception cohort study, 2400 participants, aged
      17 years or more, injured in a motor vehicle crash in New South Wales will be
      identified though hospital emergency departments, general and physiotherapy
      practitioners, police records and a government insurance regulator database.
      Participants will be initially contacted through mail. Baseline interviews will
      be conducted by telephone within 28 days of the injury and participants will be
      followed up with interviews at 6, 12 and 24 months post-injury. Health insurance
      and pharmaceutical prescription data will also be collected. DISCUSSION: The
      study results will report short and long term health and social outcomes in the
      study sample. Identification of factors associated with health and social
      outcomes following injury, including related compensation factors will provide
      evidence for improved service delivery, post-injury management, and inform policy
      development and reforms. TRIAL REGISTRATION: Australia New Zealand Clinical trial
      registry identification number--ACTRN12613000889752. Available at: ANZCTR
      Registered FISH Study.

PMID- 24564822
TI  - High prevalence of exposure to the child welfare system among street-involved
      youth in a Canadian setting: implications for policy and practice.
AB  - BACKGROUND: Street-involved youth are more likely to experience trauma and
      adverse events in childhood; however, little is known about exposure to the child
      welfare system among this vulnerable population. This study sought to examine the
      prevalence and correlates of being in government care among street-involved youth
      in Vancouver, Canada. METHODS: From September 2005 to November 2012, data were
      collected from the At-Risk Youth Study, a prospective cohort of street-involved
      youth aged 14-26 who use illicit drugs. Logistic regression analysis was employed
      to identify factors associated with a history of being in government care.
      RESULTS: Among our sample of 937 street-involved youth, 455 (49%) reported being
      in government care at some point in their childhood. In a multivariate analysis,
      Aboriginal ancestry (adjusted odds ratio [AOR] = 2.07; 95% confidence interval
      [CI]: 1.50-2.85), younger age at first "hard" substance use (AOR = 1.10; 95% CI:
      1.05-1.16), high school incompletion (AOR = 1.40; 95% CI: 1.00-1.95), having a
      parent that drank heavily or used illicit drugs (AOR = 1.48; 95% CI: 1.09-2.01),
      and experiencing physical abuse (AOR = 1.90; 95% CI: 1.22-2.96) were
      independently associated with exposure to the child welfare system. CONCLUSIONS:
      Youth with a history of being in government care appear to be at high-risk of
      adverse illicit substance-related behaviours. Evidence-based interventions are
      required to better support vulnerable children and youth with histories of being
      in the child welfare system, and prevent problematic substance use and street
      involvement among this population.

PMID- 24564823
TI  - Elucidation of bacteria found in car interiors and strategies to reduce the
      presence of potential pathogens.
AB  - The human microbiome is influenced by a number of factors, including
      environmental exposure to microbes. Because many humans spend a large amount of
      time in built environments, it can be expected that the microbial ecology of
      these environments will influence the human microbiome. In an attempt to further
      understand the microbial ecology of built environments, the microbiota of car
      interiors was analyzed using culture dependent and culture independent methods.
      While it was found that the number and type of bacteria varied widely among the
      cars and sites tested, Staphylococcus and Propionibacterium were nearly always
      the dominant genera found at the locations sampled. Because Staphylococcus is of
      particular concern to human health, the characteristics of this genus found in
      car interiors were investigated. Staphylococcus epidermidis, S. aureus, and S.
      warnerii were the most prevalent staphylococcal species found, and 22.6% of S.
      aureus strains isolated from shared community vehicles were resistant to
      methicillin. The reduction in the prevalence of pathogenic bacteria in cars by
      using silver-based antimicrobial surface coatings was also evaluated. Coatings
      containing 5% silver ion additives were applied to steering wheels, placed in
      cars for five months and were found to eliminate the presence of culturable
      pathogenic bacteria recovered from these sites relative to controls. Together,
      these results provide new insight into the microbiota found in an important built
      environment, the automobile, and potential strategies for controlling the
      presence of human pathogens. 

PMID- 24564824
TI  - Preparation and microscopy examination of alginate-poly-L-lysine-alginate
      microcapsules.
AB  - Ca-alginate-poly-l-lysine-alginate (APA-Ca) and Ba-alginate-poly-l-lysine
      alginate (APA-Ba) microcapsules were prepared and their thickness and surface
      were examined by light microscopy and scanning electron microscopy. Specifically,
      light microscopy with frozen section was used to visualize and quantify the
      thickness of APA membrane, and monitor temporal changes in the thickness of
      microcapsules during a month long culture in vitro. The section graph of APA
      microcapsule represents the accurate measurement of layer thickness of APA-Ca
      with diameter 900 +/- 100 and 500 +/- 100 MUm at 6.01 +/- 1.02 and 9.54 +/- 2.42
      MUm (p < 0.05), and layer thickness of APA-Ba with diameter 900 +/- 100 and 500
      +/- 100 MUm at 5.47 +/- 0.90 and 8.21 +/- 1.97 MUm (p < 0.05), regardless of the
      alginate composition used to generate the microcapsules. The microcapsule was
      stable during the culture for 30 days in vitro. Field emission scanning electron
      microscopy with freeze drying method was used to detect the surface and thickness
      of dried microcapsules. From the results, the outer surface of APA-Ca and APA-Ba
      membrane were smooth and dense, the film thickness of the APA-Ca was about 450
      690 nm, while the APA-Ba was approximately 335 nm. In vivo experiment, little
      significant difference was seen in the change of film thickness of microcapsules
      in intrapertioneal site for 30 days after transplantation (p > 0.05), except that
      the recovery of APA-Ba was higher than the APA-Ca microcapsules. The paper showed
      an easy method to prepare APA-Ca and APA-Ba, and examine their thickness and
      surface, which could be utilized to study other types of microcapsules.

PMID- 24564827
TI  - Analytical method evaluation and discovery of variation within maize varieties in
      the context of food safety: transcript profiling and metabolomics.
AB  - Profiling techniques such as microarrays, proteomics, and metabolomics are used
      widely to assess the overall effects of genetic background, environmental
      stimuli, growth stage, or transgene expression in plants. To assess the potential
      regulatory use of these techniques in agricultural biotechnology, we carried out
      microarray and metabolomic studies of 3 different tissues from 11 conventional
      maize varieties. We measured technical variations for both microarrays and
      metabolomics, compared results from individual plants and corresponding pooled
      samples, and documented variations detected among different varieties with
      individual plants or pooled samples. Both microarray and metabolomic technologies
      are reproducible and can be used to detect plant-to-plant and variety-to-variety
      differences. A pooling strategy lowered sample variations for both microarray and
      metabolomics while capturing variety-to-variety variation. However, unknown
      genomic sequences differing between maize varieties might hinder the application
      of microarrays. High-throughput metabolomics could be useful as a tool for the
      characterization of transgenic crops. However, researchers will have to take into
      consideration the impact on the detection and quantitation of a wide range of
      metabolites on experimental design as well as validation and interpretation of
      results. 

PMID- 24564826
TI  - Gene expression analysis of induced pluripotent stem cells from aneuploid
      chromosomal syndromes.
AB  - BACKGROUND: Human aneuploidy is the leading cause of early pregnancy loss, mental
      retardation, and multiple congenital anomalies. Due to the high mortality
      associated with aneuploidy, the pathophysiological mechanisms of aneuploidy
      syndrome remain largely unknown. Previous studies focused mostly on whether
      dosage compensation occurs, and the next generation transcriptomics sequencing
      technology RNA-seq is expected to eventually uncover the mechanisms of gene
      expression regulation and the related pathological phenotypes in human
      aneuploidy. RESULTS: Using next generation transcriptomics sequencing technology
      RNA-seq, we profiled the transcriptomes of four human aneuploid induced
      pluripotent stem cell (iPSC) lines generated from monosomy * (Turner syndrome),
      trisomy 8 (Warkany syndrome 2), trisomy 13 (Patau syndrome), and partial trisomy
      11:22 (Emanuel syndrome) as well as two umbilical cord matrix iPSC lines as
      euploid controls to examine how phenotypic abnormalities develop with aberrant
      karyotype. A total of 466 M (50-bp) reads were obtained from the six iPSC lines,
      and over 13,000 mRNAs were identified by gene annotation. Global analysis of gene
      expression profiles and functional analysis of differentially expressed (DE)
      genes were implemented. Over 5000 DE genes are determined between aneuploidy and
      euploid iPSCs respectively while 9 KEGG pathways are overlapped enriched in four
      aneuploidy samples. CONCLUSIONS: Our results demonstrate that the extra or
      missing chromosome has extensive effects on the whole transcriptome. Functional
      analysis of differentially expressed genes reveals that the genes most affected
      in aneuploid individuals are related to central nervous system development and
      tumorigenesis.

PMID- 24564828
TI  - The relationship between serum hypoxia-inducible factor 1alpha and coronary
      artery calcification in asymptomatic type 2 diabetic patients.
AB  - BACKGROUND: Hypoxia-inducible factor 1 (HIF-1), a master regulator of oxygen
      homeostasis, is a heterodimer consisting of HIF-1alpha and HIF-1beta subunits,
      and is implicated in calcification of cartilage and vasculature. The goal of this
      study was to determine the relationship between serum HIF-1alpha with coronary
      artery calcification (CAC) in patients with type 2 diabetes. METHODS: The
      subjects were 405 (262 males, 143 females, age 51.3 +/- 6.4 years) asymptomatic
      patients with type 2 diabetes mellitus. Serum HIF-1alpha and interleukin-6 (IL-6)
      levels were measured by ELISA. CAC scores were assessed by a 320-slice CT
      scanner. The subjects were divided into 4 quartiles depending on serum HIF-1alpha
      levels. RESULTS: Average serum HIF-1alpha was 184.4 +/- 66.7 pg/ml. Among
      patients with higher CAC scores, HIF-1alpha levels were also significantly
      increased (p <0.001). HIF-1alpha levels positively correlated with CRP, IL-6,
      UKPDS risk score, HbA1c, FBG, and CACS, but did not correlate with diabetes
      duration, age, and LDL. According to the multivariate analysis, HIF-1alpha levels
      significantly and independently predict the presence of CAC. ROC curve analysis
      showed that the serum HIF-1alpha level can predict the extent of CAC, but the
      specificity was lower than the traditional risk factors UKPDS and HbA1c.
      CONCLUSION: As a marker of hypoxia, serum HIF-1alpha level may be an independent
      risk factor for the presence of CAC. These findings indicate that elevated serum
      HIF-1alpha may be involved in vascular calcification in patients with type 2
      diabetes mellitus.

PMID- 24564829
TI  - Nanoscale packing differences in sphingomyelin and phosphatidylcholine revealed
      by BODIPY fluorescence in monolayers: physiological implications.
AB  - Phosphatidycholines (PC) with two saturated acyl chains (e.g., dipalmitoyl) mimic
      natural sphingomyelin (SM) by promoting raft formation in model membranes.
      However, sphingoid-based lipids, such as SM, rather than saturated-chain PCs have
      been implicated as key components of lipid rafts in biomembranes. These
      observations raise questions about the physical packing properties of the phase
      states that can be formed by these two major plasma membrane lipids with
      identical phosphocholine headgroups. To investigate, we developed a monolayer
      platform capable of monitoring changes in surface fluorescence by acquiring
      multiple spectra during measurement of a lipid force-area isotherm. We relied on
      the concentration-dependent emission changes of 4,4-difluoro-4-bora-3a,4a-diaza-s
      indacene (BODIPY)-labeled PC to detect nanoscale alterations in lipid packing and
      phase state induced by monolayer lateral compression. The BODIPY-PC probe
      contained an indacene ring with four symmetrically located methyl (Me)
      substituents to enhance localization to the lipid hydrocarbon region. Surface
      fluorescence spectra indicated changes in miscibility even when force-area
      isotherms showed no deviation from ideal mixing behavior in the surface pressure
      versus cross-sectional molecular area response. We detected slightly better
      mixing of Me4-BODIPY-8-PC with the fluid-like, liquid expanded phase of 1
      palmitoyl-2-oleoyl-PC compared to N-oleoyl-SM. Remarkably, in the gel-like,
      liquid condensed phase, Me4-BODIPY-8-PC mixed better with N-palmitoyl-SM than
      dipalmitoyl-PC, suggesting naturally abundant SMs with saturated acyl chains form
      gel-like lipid phase(s) with enhanced ability to accommodate deeply embedded
      components compared to dipalmitoyl-PC gel phase. The findings reveal a
      fundamental difference in the lateral packing properties of SM and PC that occurs
      even when their acyl chains match. 

PMID- 24564830
TI  - The Mother-Newborn Skin-to-Skin Contact Questionnaire (MSSCQ): development and
      psychometric evaluation among Iranian midwives.
AB  - BACKGROUND: Despite the benefits of mother-newborn skin-to-skin contact
      immediately after birth, it has not been universally implemented as routine care
      for healthy term neonates. Midwifes are the first person to contact the neonate
      after birth. However, there is evidence that many midwives do not perform mother
      newborn skin-to-skin contact. The aim of this study was to develop and
      psychometrically evaluate an instrument for measuring factors associated with
      mother-newborn skin-to-skin contact (MSSCQ) based on the PRECEDE-PROCEED model.
      METHODS: This was a two-phase qualitative and quantitative study. It was
      conducted during 2010 to 2012 in Tehran, Iran. In the qualitative part, 150
      midwives working in labor room participated in 19 focus group discussions in
      order to generate a preliminary item pool. Then, content and face validity were
      performed to provide a pre-final version of the questionnaire. In the
      quantitative phase, reliability (internal consistency and test-retest analysis),
      validity and factor analysis (both exploratory and confirmatory) were performed
      to assess psychometric properties of the instrument. RESULTS: A 120-item
      questionnaire was developed through the qualitative phase. It was reduced to an
      83-item after content validity. The exploratory factor analysis loaded fifteen
      factors and three constructs (predisposing, enabling and reinforcing) containing
      82 items (38, 18, and 26 statements, respectively) that jointly accounted for
      60.61% of observed variance. The Confirmatory factors analysis determined a model
      with appropriate fitness for the data. The Cronbach's alpha coefficient showed
      excellent internal consistency (alpha = 0.92), and test-retest of the scale with
      2-week intervals indicated an appropriate stability for the MSSCQ (ICC = 0.94).
      CONCLUSION: The Mother-Newborn Skin-to-Skin Contact Questionnaire (MSSCQ) is a
      reliable and valid theory-based measurement and now can be used in clinical
      practice, midwifery and nursing studies.

PMID- 24564831
TI  - Effect of oculomotor vision rehabilitation on the visual-evoked potential and
      visual attention in mild traumatic brain injury.
AB  - PRIMARY OBJECTIVE: The purpose of the experiment was to investigate the effect of
      oculomotor vision rehabilitation (OVR) on the visual-evoked potential (VEP) and
      visual attention in the mTBI population. RESEARCH DESIGN AND METHODS: Subjects (n
      = 7) were adults with a history of mild traumatic brain injury (mTBI). Each
      received 9 hours of OVR over a 6-week period. The effects of OVR on VEP amplitude
      and latency, the attention-related alpha band (8-13 Hz) power (uV(2)) and the
      clinical Visual Search and Attention Test (VSAT) were assessed before and after
      the OVR. RESULTS: After the OVR, the VEP amplitude increased and its variability
      decreased. There was no change in VEP latency, which was normal. Alpha band power
      increased, as did the VSAT score, following the OVR. CONCLUSIONS: The significant
      changes in most test parameters suggest that OVR affects the visual system at
      early visuo-cortical levels, as well as other pathways which are involved in
      visual attention.

PMID- 24564833
TI  - Thermal doping by vacancy formation in copper sulfide nanocrystal arrays.
AB  - A new approach for doping of Cu2S nanocrystal arrays using thermal treatment at
      moderate temperatures (T < 400 K) is presented. This thermal doping process
      yields conductance enhancement by 6 orders of magnitude. Local probe measurements
      prove this doping is an intraparticle effect and, moreover, tunneling
      spectroscopy data signify p-type doping. The doping mechanism is attributed to Cu
      vacancy formation, resulting in free holes. Thermal-doping temperature dependence
      exhibits an Arrhenius-like behavior, providing the vacancy formation energy of
      1.6 eV. The moderate temperature conditions for thermal doping unique to these
      nanocrystals allow patterned doping of nanocrystal films through local heating by
      a focused laser beam, toward fabrication of nanocrystal-based electronic devices.

PMID- 24564832
TI  - Organophosphate ester (OPE) flame retardants and plasticizers in the open
      Mediterranean and Black Seas atmosphere.
AB  - The presence of organophosphate ester (OPE) flame retardants and plasticizers has
      been confirmed for the first time in the atmosphere over the Mediterranean and
      Black Seas. Atmospheric aerosol samples were collected during two West-East
      oceanographic cruises across the Mediterranean and in the southwest Black Sea.
      This comprehensive assessment of baseline concentrations of aerosol phase OPEs,
      spatial distribution, and related deposition fluxes reveals levels ranging from
      0.4 to 6.0 ng m(-3) for the ?14OPEs and a lack of significant differences among
      sub-basins. Levels measured across the Mediterranean Sea and in the Black Sea are
      in the upper range or higher than those from previous reports for the marine
      atmosphere, presumably due to proximity to sources. From 13 to 260 tons of OPEs
      are estimated to be annually loaded to the Mediterranean Sea open waters from the
      atmosphere. Tris-(1-chloro-2-propyl)phosphate (TCPP) was the most abundant
      compound over the atmosphere of all the Mediterranean and Black Sea sub-basins,
      and therefore the chemical reaching surface waters at a higher extent by dry
      deposition. The atmospheric deposition fluxes of phosphorus due to OPE deposition
      is a significant fraction of known atmospheric inputs of new organic phosphorus
      (P), suggesting the relevant role that anthropogenic organic pollutants could
      play in the P cycle. 

PMID- 24564834
TI  - Computational systems biology in the big data era.
AB  - A report of the 6th IEEE International Conference on Systems Biology (IEEE
      ISB2012), 18-20 August, Xi'an, China. 

PMID- 24564835
TI  - The anti-adhesive mode of action of a purified mushroom (Lentinus edodes) extract
      with anticaries and antigingivitis properties in two oral bacterial phatogens.
AB  - BACKGROUND: In previous works we have shown that a low-molecular-mass (LMM)
      fraction from mushroom (Lentinus edodes) homogenate interferes with binding of
      Streptococcus mutans to hydroxyapatite and Prevotella intermedia to gingival
      cells. Additionally, inhibition of biofilm formation of both odonto- and
      periodonto-pathogenic bacteria and detachment from preformed biofilms have been
      described for this compound. Further purification of mushroom extract has been
      recently achieved and a sub-fraction (i.e. # 5) has been identified as containing
      the majority of the mentioned biological activities. The aim of this study was to
      characterise the bacterial receptors for the purified mushroom sub-fraction #5 in
      order to better elucidate the mode of action of this compound when interfering
      with bacterial adhesion to host surfaces or with bacteria-bacteria interactions
      in the biofilm state. METHODS: Candidate bacterial molecules to act as target of
      this compound were bacterial surface molecules involved in cell adhesion and
      biofilm formation, and, thus, we have considered cell wall associated proteins
      (CWPs), teichoic acid (TA) and lipoteichoic acid (LTA) of S. mutans, and outer
      membrane proteins (OMPs) and lipopolysaccharide (LPS) of P. intermedia. RESULTS:
      Fifteen S. mutans CWPs and TA were capable of binding sub-fraction #5, while LTA
      did not. As far as P. intermedia is concerned, we show that five OMPs interact
      with sub-fraction # 5. Capacity of binding to P. intermedia LPS was also studied
      but in this case negative results were obtained. CONCLUSIONS: Binding sub
      fraction # 5 to surface molecules of S. mutans or P. intermedia may result in
      inactivation of their physiological functions. As a whole, these results
      indicate, at molecular level, the bacterial surface alterations affecting
      adhesion and biofim formation. For these antimicrobial properties, the compound
      may find use in daily oral hygiene.

PMID- 24564837
TI  - Statistical tests to identify appropriate types of nucleotide sequence recoding
      in molecular phylogenetics.
AB  - BACKGROUND: Under a Markov model of evolution, recoding, or lumping, of the four
      nucleotides into fewer groups may permit analysis under simpler conditions but
      may unfortunately yield misleading results unless the evolutionary process of the
      recoded groups remains Markovian. If a Markov process is lumpable, then the
      evolutionary process of the recoded groups is Markovian. RESULTS: We consider
      stationary, reversible, and homogeneous Markov processes on two taxa and compare
      three tests for lumpability: one using an ad hoc test statistic, which is based
      on an index that is evaluated using a bootstrap approximation of its
      distribution; one that is based on a test proposed specifically for Markov
      chains; and one using a likelihood-ratio test. We show that the likelihood-ratio
      test is more powerful than the index test, which is more powerful than that based
      on the Markov chain test statistic. We also show that for stationary processes on
      binary trees with more than two taxa, the tests can be applied to all pairs.
      Finally, we show that if the process is lumpable, then estimates obtained under
      the recoded model agree with estimates obtained under the original model,
      whereas, if the process is not lumpable, then these estimates can differ
      substantially. We apply the new likelihood-ratio test for lumpability to two
      primate data sets, one with a mitochondrial origin and one with a nuclear origin.
      CONCLUSIONS: Recoding may result in biased phylogenetic estimates because the
      original evolutionary process is not lumpable. Accordingly, testing for
      lumpability should be done prior to phylogenetic analysis of recoded data.

PMID- 24564836
TI  - Breastfeeding promotion interventions and breastfeeding practices: a systematic
      review.
AB  - INTRODUCTION: Exclusive Breastfeeding (EBF) rates remain low in both low-income
      and high-income countries despite World Health Organization recommendations for
      EBF till 6 months. Breastfeeding has been shown to have a protective effect
      against gastrointestinal infections, among other benefits. Large-scale
      interventions focusing on educating mothers about breastfeeding have the
      potential to increase breastfeeding prevalence, especially EBF, up to recommended
      standards and also to decrease infant morbidity. METHODS: A systematic literature
      search was conducted for RCTs and quasi-experimental studies comparing
      breastfeeding education or support to routine care. The effect of interventions
      was observed for exclusive, predominant, partial and no breastfeeding rates. The
      time intervals of interest were day 1, <1 month, and 1 to 5 months. Outcome
      specific evidence was graded according to the Child Health Epidemiology Reference
      Group (CHERG) rules using the adapted Grading of Recommendations, Assessment,
      Development and Evaluation (GRADE) criteria and recommendations were made from
      studies in developing countries for inclusion into the Lives Saved Tool (LiST)
      model. RESULTS: After reviewing 4600 abstracts, 372 studies were selected for
      full text screening and 110 of these studies were finally included. Statistically
      significant increases in EBF rates as a result of breastfeeding promotion
      interventions were observed: 43% at day 1, 30% at <1 month, and 90% at 1-5
      months. Rates of 'no breastfeeding' reduced by 32% at 1 day, 30% at <1 month, and
      18% at 1-5 months. The effect of interventions on the rates of predominant and
      partial breastfeeding were non-significant. CONCLUSION: Breastfeeding education
      and/or support increased EBF rates and decreased no breastfeeding rates at birth,
      <1 month and 1-5 months. Combined individual and group counseling appeared to be
      superior to individual or group counseling alone. Interventions in developing
      countries had a greater impact than those in developed countries.

PMID- 24564839
TI  - HopDock: a probabilistic search algorithm for decoy sampling in protein-protein
      docking.
AB  - BACKGROUND: Elucidating the three-dimensional structure of a higher-order
      molecular assembly formed by interacting molecular units, a problem commonly
      known as docking, is central to unraveling the molecular basis of cellular
      activities. Though protein assemblies are ubiquitous in the cell, it is currently
      challenging to predict the native structure of a protein assembly in silico.
      METHODS: This work proposes HopDock, a novel search algorithm for protein-protein
      docking. HopDock efficiently obtains an ensemble of low-energy dimeric
      configurations, also known as decoys, that can be effectively used by ab-initio
      docking protocols. HopDock is based on the Basin Hopping (BH) framework which
      perturbs the structure of a dimeric configuration and then follows it up with an
      energy minimization to explicitly sample a local minimum of a chosen energy
      function. This process is repeated in order to sample consecutive energy minima
      in a trajectory-like fashion. HopDock employs both geometry and evolutionary
      conservation analysis to narrow down the interaction search space of interest for
      the purpose of efficiently obtaining a diverse decoy ensemble. RESULTS AND
      CONCLUSIONS: A detailed analysis and a comparative study on seventeen different
      dimers shows HopDock obtains a broad view of the energy surface near the native
      dimeric structure and samples many near-native configurations. The results show
      that HopDock has high sampling capability and can be employed to effectively
      obtain a large and diverse ensemble of decoy configurations that can then be
      further refined in greater structural detail in ab-initio docking protocols.

PMID- 24564840
TI  - Chromosome congression explained by nanoscale electrostatics.
AB  - Nanoscale electrostatic microtubule disassembly forces between positively charged
      molecules in kinetochores and negative charges on plus ends of microtubules have
      been implicated in poleward chromosome motions and may also contribute to
      antipoleward chromosome movements. We propose that chromosome congression can be
      understood in terms of antipoleward nanoscale electrostatic microtubule assembly
      forces between negatively charged microtubule plus ends and like-charged
      chromosome arms, acting in conjunction with poleward microtubule disassembly
      forces. Several other aspects of post-attachment prometaphase chromosome motions,
      as well as metaphase oscillations, are consistently explained within this
      framework. 

PMID- 24564838
TI  - Association of plasma sRAGE, but not esRAGE with lung function impairment in
      COPD.
AB  - RATIONALE: Plasma soluble Receptor for Advanced Glycation End Product (sRAGE) is
      considered as a biomarker in COPD. The contribution of endogenous sRAGE (esRAGE)
      to the pool of plasma sRAGE and the implication of both markers in COPD
      pathogenesis is however not clear yet. The aim of the current study was therefore
      to measure plasma levels of esRAGE comparative to total sRAGE in patients with
      COPD and a control group. Further, we established the relations of esRAGE and
      total sRAGE with disease specific characteristics such as lung function and DLCO,
      and with different circulating AGEs. METHODS: Plasma levels of esRAGE and sRAGE
      were measured in an 88 patients with COPD and in 55 healthy controls. FEV1
      (%predicted) and FEV1/VC (%) were measured in both groups; DLCO (%predicted) was
      measured in patients only. In this study population we previously reported that
      the AGE Nepsilon-(carboxymethyl) lysine (CML) was decreased, Nepsilon
      (carboxyethyl) lysine (CEL) increased and pentosidine was not different in plasma
      of COPD patients compared to controls. RESULTS: Plasma esRAGE (COPD: 533.9 +/-
      412.4, CONTROLS: 848.7 +/- 690.3 pg/ml; p = 0.000) was decreased in COPD compared
      to controls. No significant correlations were observed between plasma esRAGE
      levels and lung function parameters or plasma AGEs. A positive correlation was
      present between esRAGE and total sRAGE levels in the circulation. Confirming
      previous findings, total sRAGE (COPD: 512.6 +/- 403.8, CONTROLS: 1834 +/- 804.2
      pg/ml; p < 0.001) was lower in patients compared to controls and was positively
      correlated FEV1 (r = 0.235, p = 0.032), FEV1/VC (r = 0.218, p = 0.047), and DLCO
      (r = 0.308, p = 0.006). sRAGE furthermore did show a significant positive
      association with CML (r = 0.321, p = 0.003). CONCLUSION: Although plasma esRAGE
      is decreased in COPD patients compared to controls, only total sRAGE showed a
      significant and independent association with FEV1, FEV1/VC and DLCO, indicating
      that total sRAGE but not esRAGE may serve as marker of COPD disease state and
      severity.

PMID- 24564842
TI  - The dynamics of alternative pathways to compensatory substitution.
AB  - The role of epistatic interactions among loci is a central question in
      evolutionary biology and is increasingly relevant in the genomic age. While the
      population genetics of compensatory substitution have received considerable
      attention, most studies have focused on the case when natural selection is very
      strong against deleterious intermediates. In the biologically-plausible scenario
      of weak to moderate selection there exist two alternate pathways for compensatory
      substitution. In one pathway, a deleterious mutation becomes fixed prior to
      occurrence of the compensatory mutation. In the other, the two loci are
      simultaneously polymorphic. The rates of compensatory substitution along these
      two pathways and their relative probabilities are functions of the population
      size, selection strength, mutation rate, and recombination rate. In this paper
      these rates and path probabilities are derived analytically and verified using
      population genetic simulations. The expected time durations of these two paths
      are similar when selection is moderate, but not when selection is weak. The
      effect of recombination on the dynamics of the substitution process are explored
      using simulation. Using the derived rates, a phylogenetic substitution model of
      the compensatory evolution process is presented that could be used for inference
      of population genetic parameters from interspecific data. 

PMID- 24564843
TI  - Detection and classification of peaks in 5' cap RNA sequencing data.
AB  - BACKGROUND: The large-scale sequencing of 5' cap enriched cDNA promises to reveal
      the diversity of transcription initiation across entire genomes. The process of
      transcription is noisy, and there is often no single, exact start site. This
      creates the need for a fast and simple method of identifying transcription start
      peaks based on this type of data. Due to both biological and technical noise,
      many of the peaks seen are not real transcription initiation events.
      Classification of the observed peaks is an essential filtering step in the
      discovery of genuine initiation locations. RESULTS: We develop a two-stage
      approach consisting of a fast and simple algorithm based on a sliding window with
      Poisson null distribution for detecting the genomic locations of peaks, followed
      by a linear support vector machine classifier to distinguish between peaks which
      represent the initiation of transcription and peaks that do not. Comparison of
      classification performance to the best existing method based on whole genome
      segmentation showed comparable precision and improved recall. Internal features,
      which are intrinsic to the data and require no further experiments, had high
      precision and recall rates. Addition of pooled external data or matched RNA
      sequencing data resulted in gains of recall with equivalent precision.
      CONCLUSIONS: The Poisson sliding window model is an effective and fast way of
      taking the peak neighbourhood into account, and finding statistically significant
      peaks over a range of transcript expression values. It is orders of magnitude
      faster than doing whole genome segmentation. The support vector classification
      scheme has better precision and recall than existing methods. Integrating
      additional datasets is shown to provide minor gains in recall, in comparison to
      using only the cap-sequencing data.

PMID- 24564845
TI  - Polymorphism of costimulatory molecules (CTLA4, ICOS, PD.1 and CD28) and
      allogeneic hematopoietic stem cell transplantation in Iranian patients.
AB  - Costimulatory molecules are important factors determining the outcome of bone
      marrow transplant. Because the host ability in costimulatory molecule function
      may be affected by gene polymorphisms, the aim of the present study was to
      investigate the effect of CTLA4, ICOS, PD.1 and CD28 gene polymorphisms in
      outcome of bone marrow transplant patients. A total of 72 recipients were
      included in this study. CTLA4 (-1722, -1661, -318, +49), ICOS (+1720), CD28 (+17)
      and PD.1 (PD.1.3, PD.1.9) gene polymorphisms were evaluated by PCR-RFLP. The
      results showed that no differences in the distribution of all mentioned
      costimulatory molecules genotypes and alleles were observed in the Graft Versus
      Host Disease (GVHD) group compared to the non-GVHD group. After gender
      classification, there is a significant association between GA genotype (CTLA4
      1661) in male group with GVHD than without GVHD (p=0.03). Also, in this study we
      found significant associations between CC genotype and C allele of PD.1.9, and TT
      genotype and T allele of CD28 that had more frequency in grades 2-4 (p=0.04.
      p=0.02, p=0.01, p=0.003, respectively). Results indicate that the CC genotype and
      C allele of PD.1.9 and TT genotype and the T allele of CD28 are genetic risk
      factors for development of a severe grade of GVHD. This subject needs to be
      studied in different population.

PMID- 24564847
TI  - Ligand dissociation mediated charge transfer observed at colloidal W18O49
      nanoparticle interfaces.
AB  - Understanding charge transfer dynamics through the ligand shell of colloidal
      nanoparticles has been an important pursuit in solar energy conversion. While
      charge transport through ligand shells of nanoparticle films has been studied
      intensely in static dry and electrochemical systems, its influence on charge
      transfer kinetics in dispersed colloidal systems has received relatively less
      attention. This work reports the oxidation of amine passivated tungsten oxide
      nanoparticles by an organically soluble tris-(1,10-phenanthroline) iron(III)
      derivative. By following the rate of this oxidation optically via the production
      of the ferroin derivative under various reaction conditions and particle
      derivatizations, we are able to show that the fluxional ligand shells on
      dispersed, colloidal nanoparticles provide a separate and more facile pathway for
      charge transfer, in which the rate-limiting step for charge transfer is the
      ligand dissociation. Since such ligand shells are frequently required for
      nanoparticle stability, this observation has significant implications for
      colloidal nanoparticle photocatalysis. 

PMID- 24564844
TI  - Anemia and iron deficiency in COPD patients: prevalence and the effects of
      correction of the anemia with erythropoiesis stimulating agents and intravenous
      iron.
AB  - BACKGROUND: Little is known about iron deficiency (ID) and anemia in Chronic
      Obstructive Pulmonary Disease (COPD). The purposes of this study were: (i) To
      study the prevalence and treatment of anemia and ID in patients hospitalized with
      an exacerbation of COPD. (ii) to study the hematological responses and degree of
      dyspnea before and after correction of anemia with subcutaneous Erythropoiesis
      Stimulating Agents (ESAs) and intravenous (IV) iron therapy, in ambulatory anemic
      patients with both COPD and chronic kidney disease. METHODS: (i) We examined the
      hospital records of all patients with an acute exacerbation of COPD (AECOPD) to
      assess the investigation, prevalence, and treatment of anemia and ID. (ii) We
      treated 12 anemic COPD outpatients with the combination of ESAs and IV-iron,
      given once weekly for 5 weeks. One week later we measured the hematological
      response and the severity of dyspnea by Visual Analogue Scale (VAS). RESULTS: (i)
      Anemia and iron deficiency in hospitalized COPD patients: Of 107 consecutive
      patients hospitalized with an AECOPD, 47 (43.9%) were found to be anemic on
      admission. Two (3.3%) of the 60 non-anemic patients and 18 (38.3%) of the 47
      anemic patients had serum iron, percent transferrin saturation (%Tsat) and serum
      ferritin measured. All 18 (100%) anemic patients had ID, yet none had oral or IV
      iron subscribed before or during hospitalization, or at discharge. (ii)
      Intervention outpatient study: ID was found in 11 (91.7%) of the 12 anemic
      ambulatory patients. Hemoglobin (Hb), Hematocrit (Hct) and the VAS scale scores
      increased significantly with the ESAs and IV-iron treatment. There was a highly
      significant correlation between the ?Hb and ?VAS; rs = 0.71 p = 0.009 and between
      the ?Hct and ?VAS; rs = 0.8 p = 0.0014. CONCLUSIONS: ID is common in COPD
      patients but is rarely looked for or treated. Yet correction of the ID in COPD
      patients with ESAs and IV iron can improve the anemia, the ID, and may improve
      the dyspnea.

PMID- 24564841
TI  - Rational design for multifunctional non-liposomal lipid-based nanocarriers for
      cancer management: theory to practice.
AB  - Nanomedicines have gained more and more attention in cancer therapy thanks to
      their ability to enhance the tumour accumulation and the intracellular uptake of
      drugs while reducing their inactivation and toxicity. In parallel, nanocarriers
      have been successfully employed as diagnostic tools increasing imaging resolution
      holding great promises both in preclinical research and in clinical settings.
      Lipid-based nanocarriers are a class of biocompatible and biodegradable vehicles
      that provide advanced delivery of therapeutic and imaging agents, improving
      pharmacokinetic profile and safety. One of most promising engineering challenges
      is the design of innovative and versatile multifunctional targeted
      nanotechnologies for cancer treatment and diagnosis. This review aims to
      highlight rational approaches to design multifunctional non liposomal lipid-based
      nanocarriers providing an update of literature in this field. 

PMID- 24564848
TI  - Building a web-based tool to support clinical decisions in the control of
      Chlamydia trachomatis and Neisseria gonorrhoeae infections.
AB  - Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (GC) are the agents of two
      common, sexually transmitted diseases afflicting women in the United States
      (http://www.cdc.gov). We designed a novel web-based application that offers
      simple recommendations to help optimize medical outcomes with CT and GC
      prevention and control programs. This application takes population groups,
      prevalence rates, parameters for available screening assays and treatment
      regimens (costs, sensitivity, and specificity), as well as budget limits as
      inputs. Its output suggests optimal screening and treatment strategies for
      selected at-risk groups, commensurate with the clinic's budget allocation.
      Development of this tool illustrates how a clinical informatics application based
      on rigorous mathematics might have a significant impact on real-world clinical
      issues. 

PMID- 24564846
TI  - KCF-S: KEGG Chemical Function and Substructure for improved interpretability and
      prediction in chemical bioinformatics.
AB  - BACKGROUND: In order to develop hypothesis on unknown metabolic pathways,
      biochemists frequently rely on literature that uses a free-text format to
      describe functional groups or substructures. In computational chemistry or
      cheminformatics, molecules are typically represented by chemical descriptors,
      i.e., vectors that summarize information on its various properties. However, it
      is difficult to interpret these chemical descriptors since they are not directly
      linked to the terminology of functional groups or substructures that the
      biochemists use. METHODS: In this study, we used KEGG Chemical Function (KCF)
      format to computationally describe biochemical substructures in seven attributes
      that resemble biochemists' way of dealing with substructures. RESULTS: We
      established KCF-S (KCF-and-Substructures) format as an additional structural
      information of KCF. Applying KCF-S revealed the specific appearance of
      substructures from various datasets of molecules that describes the
      characteristics of the respective datasets. Structure-based clustering of
      molecules using KCF-S resulted the clusters in which molecular weights and
      structures were less diverse than those obtained by conventional chemical
      fingerprints. We further applied KCF-S to find the pairs of molecules that are
      possibly converted to each other in enzymatic reactions, and KCF-S clearly
      improved predictive performance than that presented previously. CONCLUSIONS: KCF
      S defines biochemical substructures with keeping interpretability, suggesting the
      potential to apply more studies on chemical bioinformatics. KCF and KCF-S can be
      automatically converted from Molfile format, enabling to deal with molecules from
      any data sources.

PMID- 24564849
TI  - Isotopic composition and distribution of plutonium in northern South China Sea
      sediments revealed continuous release and transport of Pu from the Marshall
      Islands.
AB  - The (239+240)Pu activities and (240)Pu/(239)Pu atom ratios in sediments of the
      northern South China Sea and its adjacent Pearl River Estuary were determined to
      examine the spatial and temporal variations of Pu inputs. We clarified that Pu in
      the study area is sourced from a combination of global fallout and close-in
      fallout from the Pacific Proving Grounds in the Marshall Islands where above
      ground nuclear weapons testing was carried out during the period of 1952-1958.
      The latter source dominated the Pu input in the 1950s, as evidenced by elevated
      (240)Pu/(239)Pu atom ratios (>0.30) in a dated sediment core. Even after the
      1950s, the Pacific Proving Grounds was still a dominant Pu source due to
      continuous transport of remobilized Pu from the Marshall Islands, about 4500 km
      away, along the North Equatorial Current followed by the transport of the
      Kuroshio current and its extension into the South China Sea through the Luzon
      Strait. Using a simple two end-member mixing model, we have quantified the
      contributions of Pu from the Pacific Proving Grounds to the northern South China
      Sea shelf and the Pearl River Estuary are 68% +/- 1% and 30% +/- 5%,
      respectively. This study also confirmed that there were no clear signals of Pu
      from the Fukushima Daiichi Nuclear Power Plant accident impacting the South China
      Sea. 

PMID- 24564850
TI  - The influence of working memory on the anger superiority effect.
AB  - The anger superiority effect shows that an angry face is detected more
      efficiently than a happy face. However, it is still controversial whether
      attentional allocation to angry faces is a bottom-up process or not. We
      investigated whether the anger superiority effect is influenced by top-down
      control, especially working memory (WM). Participants remembered a colour and
      then searched for differently coloured facial expressions. Just holding the
      colour information in WM did not modulate the anger superiority effect. However,
      when increasing the probabilities of trials in which the colour of a target face
      matched the colour held in WM, participants were inclined to direct attention to
      the target face regardless of the facial expression. Moreover, the knowledge of
      high probability of valid trials eliminated the anger superiority effect. These
      results suggest that the anger superiority effect is modulated by top-down
      effects of WM, the probability of events and expectancy about these
      probabilities. 

PMID- 24564852
TI  - Purple sweet potato (Ipomoea batatas L.) anthocyanins: preventive effect on acute
      and subacute alcoholic liver damage and dealcoholic effect.
AB  - This study aimed to investigate the dealcoholic effect and preventive effect of
      anthocyanins from purple sweet potato (PSPAs) on acute and subacute alcoholic
      liver damage (ALD). Seven-week-old male inbred mice were grouped into five
      groups: control group (without PSPAs and ethanol treatments), model group (with
      ethanol treatment only), low-dose group (50 mg PSPAs/kg body weight), middle-dose
      group (125 mg PSPAs/kg body weight), and high-dose group (375 mg PSPAs/kg body
      weight), and the mice in all groups were administered intragastrically.
      Biochemical parameters of serum and liver were determined, and the
      histopathological changes of liver tissue were also analyzed. Results showed that
      all tested parameters were ameliorated after consumption of PSPAs. Therefore,
      PSPAs have preventive effect on acute and subacute ALD. It is suggested that
      PSPAs could be used as a supplementary reagent during prophylactic and curative
      managements of ALD.

PMID- 24564853
TI  - A genetic tool to manipulate litter size.
AB  - INTRODUCTION: Experimental litter size manipulations are often not problem free.
      Typically conducted shortly after birth or oviposition, they do not account for
      the energy already invested into the production of the offspring. Such effects
      make it difficult to interpret the results from experimental litter size
      manipulations and therefore to study optimality of litter or clutch size, a long
      debated topic in evolutionary biology. RESULTS: We propose the use of a mating
      design based on a selfish genetic element, the t haplotype, to reduce litter size
      in an eutherian mammal, the house mouse. Most t haplotypes are recessive lethal
      and therefore lead to the death of all homozygous embryos. Litter sizes can be
      reduced by up to 50% by pairing a +/t female with a +/t male instead of a +/+
      male. CONCLUSIONS: This method allows litter size manipulation before birth
      without the use of invasive techniques, therefore providing an excellent tool for
      studying optimal litter size and ultimately helping to understand life history
      strategies.

PMID- 24564851
TI  - Social and health policies or interventions to tackle health inequalities in
      European cities: a scoping review.
AB  - BACKGROUND: Health inequalities can be tackled with appropriate health and social
      policies, involving all community groups and governments, from local to global.
      The objective of this study was to carry out a scoping review on social and
      health policies or interventions to tackle health inequalities in European cities
      published in scientific journals. METHODS: Scoping review. The search was done in
      "PubMed" and the "Sociological Abstracts" database and was limited to articles
      published between 1995 and 2011. The inclusion criteria were: interventions had
      to take place in European cities and they had to state the reduction of health
      inequalities among their objectives. RESULTS: A total of 54 papers were included,
      of which 35.2% used an experimental design, and 74.1% were carried out in the
      United Kingdom. The whole city was the setting in 27.8% of them and 44.4% were
      based on promoting healthy behaviours. Adults and children were the most frequent
      target population and half of the interventions had a universal approach and the
      other half a selective one. Half of the interventions were evaluated and showed
      positive results. CONCLUSIONS: Although health behaviours are not the main
      determinants of health inequalities, the majority of the selected documents were
      based on evaluations of interventions focusing on them.

PMID- 24564854
TI  - Free radical metabolism of methyleugenol and related compounds.
AB  - Methyleugenol, the methyl ether of eugenol, both of which are flavorant
      constituents of spices, has been listed by the National Toxicology Program's
      Report on Carcinogens as reasonably anticipated to be a human carcinogen. This
      finding is based on the observation of increased incidence of malignant tumors at
      multiple tissue sites in experimental animals of different species. By contrast,
      eugenol is not listed. In this study, we show that both methyleugenol and eugenol
      readily undergo peroxidative metabolism in vitro to form free radicals with large
      hyperfine interactions of the methylene allylic hydrogen atoms. These large
      hyperfine splittings indicate large electron densities adjacent to those hydrogen
      atoms. Methyleugenol undergoes autoxidation such that the commercial product
      contains 10-30 mg/L hydroperoxide and is capable of activating peroxidases
      without the presence of added hydrogen peroxide. Additionally, the hydroperoxide
      is not a good substrate for catalase, which demonstrates that these antioxidant
      defenses will not be effective in protecting against methyleugenol exposure.

PMID- 24564855
TI  - Collective prediction of protein functions from protein-protein interaction
      networks.
AB  - BACKGROUND: Automated assignment of functions to unknown proteins is one of the
      most important task in computational biology. The development of experimental
      methods for genome scale analysis of molecular interaction networks offers new
      ways to infer protein function from protein-protein interaction (PPI) network
      data. Existing techniques for collective classification (CC) usually increase
      accuracy for network data, wherein instances are interlinked with each other,
      using a large amount of labeled data for training. However, the labeled data are
      time-consuming and expensive to obtain. On the other hand, one can easily obtain
      large amount of unlabeled data. Thus, more sophisticated methods are needed to
      exploit the unlabeled data to increase prediction accuracy for protein function
      prediction. RESULTS: In this paper, we propose an effective Markov chain based CC
      algorithm (ICAM) to tackle the label deficiency problem in CC for interrelated
      proteins from PPI networks. Our idea is to model the problem using two distinct
      Markov chain classifiers to make separate predictions with regard to attribute
      features from protein data and relational features from relational information.
      The ICAM learning algorithm combines the results of the two classifiers to
      compute the ranks of labels to indicate the importance of a set of labels to an
      instance, and uses an ICA framework to iteratively refine the learning models for
      improving performance of protein function prediction from PPI networks in the
      paucity of labeled data. CONCLUSION: Experimental results on the real-world Yeast
      protein-protein interaction datasets show that our proposed ICAM method is better
      than the other ICA-type methods given limited labeled training data. This
      approach can serve as a valuable tool for the study of protein function
      prediction from PPI networks.

PMID- 24564856
TI  - Determinants of satisfaction 1 year after total hip arthroplasty: the role of
      expectations fulfilment.
AB  - BACKGROUND: Between 7% and 15% of patients are dissatisfied after total hip
      arthroplasty (THA). To assess predictors and postoperative determinants of
      satisfaction and expectation fulfilment one year after (THA). METHODS: Before THA
      surgery, 132 patients from three tertiary care centres and their surgeons were
      interviewed to assess their expectations using the Hospital for Special Surgery
      Total Hip Replacement Expectations Survey (THR survey). One year after surgery,
      patients (n = 123) were contacted by phone to complete a questionnaire on
      expectation fulfilment (THR survey), satisfaction, functional outcome (Womac),
      and health-related quality of life (SF 12). Univariate and multivariate analyses
      were performed. RESULTS: Preoperative predictors of satisfaction were a good
      mental wellbeing (adjusted OR 1.09 [1.02; 1.16], p = 0.01) and optimistic
      surgeons expectations (1.07 [1.01; 1.14], p = 0.02). The main postoperative
      determinant of satisfaction was the fulfilment of patient's expectations (1.08
      [1.04; 1.12], p < 0.001). Expectation fulfilment could be predicted before
      surgery by young age (regression coefficient -0.55 [-0.88; -0.21], p = 0.002),
      good physical function (-0.96 [-1.82; -0.10], p = 0.03) and good mental wellbeing
      (0.56 [0.14; 0.99], p = 0.01). Postoperative determinants of expectation
      fulfilment were functional outcome (-2.10 [-2.79; -1.42], p <0.001) and pain
      relief (-14.83 [-22.38; -7.29], p < 0.001). CONCLUSION: To improve patient
      satisfaction after THA, patients' expectations and their fulfilment need to be
      carefully addressed. Patients with low mental wellbeing or physical function
      should be identified and specifically informed on expected surgical outcome.
      Surgeons' expectations are predictive of satisfaction and information should aim
      to lower discrepancy between surgeons' and patients' expectations.

PMID- 24564857
TI  - Cell labeling with magnetic nanoparticles: opportunity for magnetic cell imaging
      and cell manipulation.
AB  - This tutorial describes a method of controlled cell labeling with citrate-coated
      ultra small superparamagnetic iron oxide nanoparticles. This method may provide
      basically all kinds of cells with sufficient magnetization to allow cell
      detection by high-resolution magnetic resonance imaging (MRI) and to enable
      potential magnetic manipulation. In order to efficiently exploit labeled cells,
      quantify the magnetic load and deliver or follow-up magnetic cells, we herein
      describe the main requirements that should be applied during the labeling
      procedure. Moreover we present some recommendations for cell detection and
      quantification by MRI and detail magnetic guiding on some real-case studies in
      vitro and in vivo. 

PMID- 24564858
TI  - HMPAS: Human Membrane Protein Analysis System.
AB  - BACKGROUND: Membrane proteins perform essential roles in diverse cellular
      functions and are regarded as major pharmaceutical targets. The significance of
      membrane proteins has led to the developing dozens of resources related with
      membrane proteins. However, most of these resources are built for specific well
      known membrane protein groups, making it difficult to find common and specific
      features of various membrane protein groups. METHODS: We collected human membrane
      proteins from the dispersed resources and predicted novel membrane protein
      candidates by using ortholog information and our membrane protein classifiers.
      The membrane proteins were classified according to the type of interaction with
      the membrane, subcellular localization, and molecular function. We also made new
      feature dataset to characterize the membrane proteins in various aspects
      including membrane protein topology, domain, biological process, disease, and
      drug. Moreover, protein structure and ICD-10-CM based integrated disease and drug
      information was newly included. To analyze the comprehensive information of
      membrane proteins, we implemented analysis tools to identify novel sequence and
      functional features of the classified membrane protein groups and to extract
      features from protein sequences. RESULTS: We constructed HMPAS with 28,509
      collected known membrane proteins and 8,076 newly predicted candidates. This
      system provides integrated information of human membrane proteins individually
      and in groups organized by 45 subcellular locations and 1,401 molecular
      functions. As a case study, we identified associations between the membrane
      proteins and diseases and present that membrane proteins are promising targets
      for diseases related with nervous system and circulatory system. A web-based
      interface of this system was constructed to facilitate researchers not only to
      retrieve organized information of individual proteins but also to use the tools
      to analyze the membrane proteins. CONCLUSIONS: HMPAS provides comprehensive
      information about human membrane proteins including specific features of certain
      membrane protein groups. In this system, user can acquire the information of
      individual proteins and specified groups focused on their conserved sequence
      features, involved cellular processes, and diseases. HMPAS may contribute as a
      valuable resource for the inference of novel cellular mechanisms and
      pharmaceutical targets associated with the human membrane proteins. HMPAS is
      freely available at http://fcode.kaist.ac.kr/hmpas.

PMID- 24564860
TI  - Separate electronic attenuation allowing a spin-component-scaled second-order
      Moller-Plesset theory to be effective for both thermochemistry and noncovalent
      interactions.
AB  - Spin-component-scaled (SCS) second-order Moller-Plesset perturbation theory (MP2)
      improves the treatment of thermochemistry and noncovalent interactions relative
      to MP2, although the optimal scaling coefficients are quite different for
      thermochemistry versus noncovalent interactions. This work reconciles these two
      different scaling regimes for SCS-MP2 by using two different length scales for
      electronic attenuation of the two spin components. The attenuation parameters and
      scaling coefficients are optimized in the aug-cc-pVTZ (aTZ) basis using the S66
      database of intermolecular interactions and the W4-11 database of
      thermochemistry. Transferability tests are performed for atomization energies and
      barrier heights, as well as on further test sets for inter- and intramolecular
      interactions. SCS dual-attenuated MP2 in the aTZ basis, SCS-MP2(2terfc, aTZ),
      performs similarly to SCS-MP2/aTZ for thermochemistry while frequently
      outperforming MP2 at the complete basis set limit (CBS) for nonbonded
      interactions. 

PMID- 24564862
TI  - Electron conductive and proton permeable vertically aligned carbon nanotube
      membranes.
AB  - We report the fabrication of membranes hundreds of micrometers thick that
      demonstrate efficient electron conduction and proton transport through vertically
      aligned arrays of multiwalled carbon nanotubes (NTs) impregnated by epoxy.
      Electrical transport was Ohmic with a conductivity of 495 mS cm(-1). Protons
      traversed the membrane through the NT bore with a current of 5.84 * 10(-6) A.
      Good electron and proton transport, chemical robustness, and simple fabrication
      suggest NT membranes have potential in artificial photosynthesis applications. 

PMID- 24564859
TI  - Co-expression network analysis identifies Spleen Tyrosine Kinase (SYK) as a
      candidate oncogenic driver in a subset of small-cell lung cancer.
AB  - BACKGROUND: Oncogenic mechanisms in small-cell lung cancer remain poorly
      understood leaving this tumor with the worst prognosis among all lung cancers.
      Unlike other cancer types, sequencing genomic approaches have been of limited
      success in small-cell lung cancer, i.e., no mutated oncogenes with potential
      driver characteristics have emerged, as it is the case for activating mutations
      of epidermal growth factor receptor in non-small-cell lung cancer. Differential
      gene expression analysis has also produced SCLC signatures with limited
      application, since they are generally not robust across datasets. Nonetheless,
      additional genomic approaches are warranted, due to the increasing availability
      of suitable small-cell lung cancer datasets. Gene co-expression network
      approaches are a recent and promising avenue, since they have been successful in
      identifying gene modules that drive phenotypic traits in several biological
      systems, including other cancer types. RESULTS: We derived an SCLC-specific
      classifier from weighted gene co-expression network analysis (WGCNA) of a lung
      cancer dataset. The classifier, termed SCLC-specific hub network (SSHN), robustly
      separates SCLC from other lung cancer types across multiple datasets and multiple
      platforms, including RNA-seq and shotgun proteomics. The classifier was also
      conserved in SCLC cell lines. SSHN is enriched for co-expressed signaling network
      hubs strongly associated with the SCLC phenotype. Twenty of these hubs are
      actionable kinases with oncogenic potential, among which spleen tyrosine kinase
      (SYK) exhibits one of the highest overall statistical associations to SCLC. In
      patient tissue microarrays and cell lines, SCLC can be separated into SYK
      positive and -negative. SYK siRNA decreases proliferation rate and increases cell
      death of SYK-positive SCLC cell lines, suggesting a role for SYK as an oncogenic
      driver in a subset of SCLC. CONCLUSIONS: SCLC treatment has thus far been limited
      to chemotherapy and radiation. Our WGCNA analysis identifies SYK both as a
      candidate biomarker to stratify SCLC patients and as a potential therapeutic
      target. In summary, WGCNA represents an alternative strategy to large scale
      sequencing for the identification of potential oncogenic drivers, based on a
      systems view of signaling networks. This strategy is especially useful in cancer
      types where no actionable mutations have emerged.

PMID- 24564861
TI  - A comparison of statistical methods for the detection of hepatocellular carcinoma
      based on serum biomarkers and clinical variables.
AB  - BACKGROUND: Currently, a surgical approach is the best curative treatment for
      those with hepatocellular carcinoma (HCC). However, this requires HCC detection
      and removal of the lesion at an early stage. Unfortunately, most cases of HCC are
      detected at an advanced stage because of the lack of accurate biomarkers that can
      be used in the surveillance of those at risk. It is believed that biomarkers that
      could detect HCC early will play an important role in the successful treatment of
      HCC. METHODS: In this study, we analyzed serum levels of alpha fetoprotein, Golgi
      protein, fucosylated alpha-1-anti-trypsin, and fucosylated kininogen from 113
      patients with cirrhosis and 164 serum samples from patients with cirrhosis plus
      HCC. We utilized two different methods, namely, stepwise penalized logistic
      regression (stepPLR) and model-based classification and regression trees (mob),
      along with the inclusion of clinical and demographic factors such as age and
      gender, to determine if these improved algorithms could be used to increase the
      detection of cancer. RESULTS AND DISCUSSION: The performance of multiple
      biomarkers was found to be better than that of individual biomarkers. Using
      several statistical methods, we were able to detect HCC in the background of
      cirrhosis with an area under the receiver operating characteristic curve of at
      least 0.95. stepPLR and mob demonstrated better predictive performance relative
      to logistic regression (LR), penalized LR and classification and regression trees
      (CART) used in our prior study based on three-fold cross-validation and leave one
      out cross-validation. In addition, mob provided unparalleled intuitive
      interpretation of results and potential cut-points for biomarker levels. The
      inclusion of age and gender improved the overall performance of both methods
      among all models considered, while the stratified male-only subset provided the
      best overall performance among all methods and models considered. CONCLUSIONS: In
      addition to multiple biomarkers, the incorporation of age and gender into
      statistical models significantly improved their predictive performance in the
      detection of HCC.

PMID- 24564864
TI  - Liver X receptor activation induces apoptosis of melanoma cell through caspase
      pathway.
AB  - Liver X receptors (LXRs) are nuclear receptors that function as ligand-activated
      transcription factors regulating lipid metabolism and inflammation. Recent
      discoveries found LXRs could regulate tumor growth in a variety of cancer cell
      lines. In this study, we investigated the effect of LXR activation on melanoma
      cell proliferation and apoptosis both in vitro and in vivo. Treatment of B16F10
      and A-375 melanoma cells with synthetic LXR agonist T0901317 significantly
      inhibited the proliferation of melanoma cells in vitro. Meanwhile, T0901317
      induced the apoptosis of B16F10 melanoma cells in a dose-dependent manner.
      Furthermore, western blot assay showed that the pro-apoptotic effect of T0901317
      on B16F10 melanoma cells was mediated through caspase-3 pathway. Oral
      administration of T0901317 inhibited the growth of B16F10 melanoma in C56BL/6
      mice. Altogether, this study demonstrates the critical role of LXRs in the
      regulation of melanoma growth and presents the LXR agonist T0901317 as a
      potential anti-melanoma agent. 

PMID- 24564863
TI  - Innovations in preclinical biology: ex vivo engineering of a human kidney tissue
      microperfusion system.
AB  - Kidney disease is a public health problem that affects more than 20 million
      people in the US adult population, yet little is understood about the impact of
      kidney disease on drug disposition. Consequently there is a critical need to be
      able to model the human kidney and other organ systems, to improve our
      understanding of drug efficacy, safety, and toxicity, especially during drug
      development. The kidneys in general, and the proximal tubule specifically, play a
      central role in the elimination of xenobiotics. With recent advances in molecular
      investigation, considerable information has been gathered regarding the substrate
      profiles of the individual transporters expressed in the proximal tubule.
      However, we have little knowledge of how these transporters coupled with
      intracellular enzymes and influenced by metabolic pathways form an efficient
      secretory and reabsorptive mechanism in the renal tubule. Proximal tubular
      secretion and reabsorption of xenobiotics is critically dependent on interactions
      with peritubular capillaries and the interstitium. We plan to robustly model the
      human kidney tubule interstitium, utilizing an ex vivo three-dimensional modular
      microphysiological system with human kidney-derived cells. The microphysiological
      system should accurately reflect human physiology, be usable to predict renal
      handling of xenobiotics, and should assess mechanisms of kidney injury, and the
      biological response to injury, from endogenous and exogenous intoxicants. 

PMID- 24564865
TI  - Diaryl and heteroaryl sulfides: synthesis via sulfenyl chlorides and evaluation
      as selective anti-breast-cancer agents.
AB  - A mild protocol for the synthesis of diaryl and heteroaryl sulfides is described.
      In a one-pot procedure, thiols are converted to sulfenyl chlorides and reacted
      with arylzinc reagents. This method tolerates functional groups including aryl
      fluorides and chlorides, ketones, as well as N-heterocycles including
      pyrimidines, imidazoles, tetrazoles, and oxadiazoles. Two compounds synthesized
      by this method exhibited selective activity against the MCF-7 breast cancer cell
      line in the micromolar range. 

PMID- 24564867
TI  - HSA: a heuristic splice alignment tool.
AB  - BACKGROUND: RNA-Seq methodology is a revolutionary transcriptomics sequencing
      technology, which is the representative of Next generation Sequencing (NGS). With
      the high throughput sequencing of RNA-Seq, we can acquire much more information
      like differential expression and novel splice variants from deep sequence
      analysis and data mining. But the short read length brings a great challenge to
      alignment, especially when the reads span two or more exons. METHODS: A two steps
      heuristic splice alignment tool is generated in this investigation. First, map
      raw reads to reference with unspliced aligner--BWA; second, split initial
      unmapped reads into three equal short reads (seeds), align each seed to the
      reference, filter hits, search possible split position of read and extend hits to
      a complete match. RESULTS: Compare with other splice alignment tools like
      SOAPsplice and Tophat2, HSA has a better performance in call rate and efficiency,
      but its results do not as accurate as the other software to some extent.
      CONCLUSIONS: HSA is an effective spliced aligner of RNA-Seq reads mapping, which
      is available at https://github.com/vlcc/HSA.

PMID- 24564866
TI  - Paederia foetida Linn. leaf extract: an antihyperlipidemic, antihyperglycaemic
      and antioxidant activity.
AB  - BACKGROUND: The primary objective of the present investigation is to evaluate the
      antidiabetic, antihyperlidemic and antioxidant activity of the methanolic extract
      of the Paederia foetida Linn. (PF) leaf extract in the streptozotocin induced
      diabetic rats. METHODS: Single intraperitoneal injection (IP) of streptozotocin
      (60 mg/kg body weight) was used for induction of diabetes is swiss albino (wistar
      strain) rats. The induction of diabetes was confirmed after 3 days as noticing
      the increase in blood sugar level of tested rats. PF at a once a daily dose of
      100 mg/kg, 250 mg/kg, 500 mg/kg, p.o. along with glibenclamide 10 mg/kg, p.o. was
      also given for 28 days. On the 28th day rats from all the groups fasted overnight
      fasted and the blood was collected from the puncturing the retro orbit of the eye
      under mild anesthetic condition. There collected blood sample was used to
      determine the antihyperlipidemic, hypoglycemic and antioxidant parameters.
      RESULTS: The oral acute toxicity studies did not show any toxic effect till the
      dose at 2000 mg/kg. While oral glucose tolerance test showed better glucose
      tolerance in tested rats. The statistical data indicated that the different dose
      of the PF significantly increased the body weight, hexokinase, plasma insulin,
      high density lipoprotein cholesterol, superoxide dismutase, catalase and
      glutathione peroxides. It also decreases the level of fasting blood glucose,
      total cholesterol, triglycerides, low density lipoprotein cholesterol, very low
      density lipoprotein cholesterol, malonaldehyde, glucose-6-phosphate, fructose-1-6
      biphosphate and glycated hemoglobin in STZ induced diabetic rats. The
      histopathology of STZ induce diabetic rats, as expected the test dose of PF
      extract considerably modulates the pathological condition of various vital organ
      viz. heart, kidney, liver, pancreas as shown in the histopathology examinations.
      CONCLUSIONS: Our investigation has clearly indicated that the leaf extract of
      Paederia foetida Linn. showed remarkable antihyperglycemic activity due to its
      possible systematic effect involving in the pancreatic and extra pancreatic
      mechanism. Forever, the antihyperlipidemic activity was exerted possible by
      lowering the higher level of lipid profile and decreasing the intercalated disc
      space in the heart. The antioxidant activity of extract was due to inhibition of
      lipid peroxidation and increasing the SOD, GPx and CAT. It was corroborate that
      the extract shown the Paederia foetida Linn leaves potential to be act as
      antidiabetic, antihyperlipidemic and antioxidant properties.

PMID- 24564868
TI  - A review of research on salivary biomarkers for oral cancer detection.
AB  - Using saliva for disease diagnostics and health surveillance is a promising
      approach as collecting saliva is relatively easy and non-invasive. Over the past
      two decades, using salivary biomarkers specifically for early cancer detection
      has attracted much research interest, especially for cancers occurring in the
      oral cavity and oropharynx, for which the five-year survival rate (62%) is still
      one of the lowest among all major human cancers. More than 90% of oral cancers
      are oral squamous cell carcinoma (OSCC) and the standard method for detection is
      through a comprehensive clinical examination by oral healthcare professionals.
      Despite the fact that the oral cavity is easily accessible, most OSCCs are not
      diagnosed until an advanced stage, which is believed to be the major reason for
      the low survival rate, and points to the urgent need for clinical diagnostic aids
      for early detection of OSCC. Thus, much research effort has been dedicated to
      investigating potential salivary biomarkers for OSCC, and more than 100 such
      biomarkers have been reported in the literature. However, some important issues
      and challenges have emerged that require solutions and further research in order
      to find reliable OSCC salivary biomarkers for clinical use. This review article
      provides an up-to-date list of potential OSCC salivary biomarkers reported as of
      the fall of 2013, and discusses those emerging issues. By raising the awareness
      of these issues on the part of both researchers and clinicians, it is hoped that
      reliable, specific and sensitive salivary biomarkers may be found soon-and not
      only biomarkers for early OSCC detection but also for detecting other types of
      cancers or even for monitoring non-cancerous disease activity. 

PMID- 24564870
TI  - Scalable prediction of compound-protein interactions using minwise hashing.
AB  - The identification of compound-protein interactions plays key roles in the drug
      development toward discovery of new drug leads and new therapeutic protein
      targets. There is therefore a strong incentive to develop new efficient methods
      for predicting compound-protein interactions on a genome-wide scale. In this
      paper we develop a novel chemogenomic method to make a scalable prediction of
      compound-protein interactions from heterogeneous biological data using minwise
      hashing. The proposed method mainly consists of two steps: 1) construction of new
      compact fingerprints for compound-protein pairs by an improved minwise hashing
      algorithm, and 2) application of a sparsity-induced classifier to the compact
      fingerprints. We test the proposed method on its ability to make a large-scale
      prediction of compound-protein interactions from compound substructure
      fingerprints and protein domain fingerprints, and show superior performance of
      the proposed method compared with the previous chemogenomic methods in terms of
      prediction accuracy, computational efficiency, and interpretability of the
      predictive model. All the previously developed methods are not computationally
      feasible for the full dataset consisting of about 200 millions of compound
      protein pairs. The proposed method is expected to be useful for virtual screening
      of a huge number of compounds against many protein targets. 

PMID- 24564869
TI  - Residue correlation networks in nuclear receptors reflect functional
      specialization and the formation of the nematode-specific P-box.
AB  - BACKGROUND: Nuclear receptors (NRs) are transcription factors which bind small
      hormones, whose evolutionary history and the presence of different functional
      surfaces makes them an interesting target for a correlation based analysis.
      RESULTS: Correlation analysis of ligand binding domains shows that correlated
      residue subsets arise from the differences between functional sites in different
      nuclear receptor subfamilies. For the DNA binding domain, particularly, the
      analysis shows that the main source of correlation comes from residues that
      regulate hormone response element specificity, and one of the conserved residue
      sub-sets arises due to the presence of an unusual sequence for the DNA binding
      motif known as P-box in nematodes, suggesting the existence of different DBD-DNA
      specificities in nuclear receptors. CONCLUSIONS: We conclude that DNA specificity
      and functional surface specialization has independently driven nuclear receptor
      evolution, and suggest possible binding modes for the class of divergent nuclear
      receptors in nematodes.

PMID- 24564872
TI  - Atmospheric emission inventory of hazardous trace elements from China's coal
      fired power plants--temporal trends and spatial variation characteristics.
AB  - Coal-fired power plants are the important sources of anthropogenic atmospheric
      releases of various hazardous trace elements (HTE) because a large quantity of
      emissions can cause wide dispersion and possible long-distance transportation. To
      obtain the temporal trends and spatial variation characteristics of various HTE
      discharged from coal-fired power plants of China, a multiple-year comprehensive
      emission inventory of HTE including Hg, As, Se, Pb, Cd, Cr, Ni, and Sb has been
      established for the period 2000-2010. Thanks to the cobenefit removal effects of
      conventional particulate matter/sulfur dioxide/nitrogen oxides (PM/SO2/NOx)
      control devices, emissions of these 8 toxic elements have shown a gradual decline
      since the peak in 2006. The total emissions of Hg, As, Se, Pb, Cd, Cr, Ni, and Sb
      are substantial and are estimated at about 118.54, 335.45, 459.4, 705.45, 13.34,
      505.03, 446.42, and 82.33 tons (t), respectively, in 2010. Shandong, Jiangsu,
      Shanxi, and Hebei always rank among the top ten provinces with the highest
      emissions. Further, future emissions for 2015 and 2020 are projected with
      scenario analysis. Advanced technologies and integrated management strategies to
      control HTE are in great need. 

PMID- 24564871
TI  - Satisfaction with life during pregnancy and early motherhood in first-time
      mothers of advanced age: a population-based longitudinal study.
AB  - BACKGROUND: The trend to delay motherhood to the age of 30 and beyond is
      established in most high-income countries but relatively little is known about
      potential effects on maternal emotional well-being. This study investigates
      satisfaction with life during pregnancy and the first three years of motherhood
      in women expecting their first baby at an advanced and very advanced age.
      METHODS: The study was based on the National Norwegian Mother and Child Cohort
      Study (MoBa) conducted by the Norwegian Institute of Public Health. Data on 18
      565 nulliparous women recruited in the second trimester 1999-2008 were used. Four
      questionnaires were completed: at around gestational weeks 17 and 30, and at six
      months and three years after the birth. Medical data were retrieved from the
      national Medical Birth Register. Advanced age was defined as 32-37 years, very
      advanced age as >=38 years and the reference group as 25-31 years. The
      distribution of satisfaction with life from age 25 to >=40 years was
      investigated, and the mean satisfaction with life at the four time points was
      estimated. Logistic regression analyses based on generalised estimation equations
      were used to investigate associations between advanced and very advanced age and
      satisfaction with life when controlling for socio-demographic factors. RESULTS:
      Satisfaction with life decreased from around age 28 to age 40 and beyond, when
      measured in gestational weeks 17 and 30, and at six months and three years after
      the birth. When comparing women of advanced and very advanced age with the
      reference group, satisfaction with life was slightly reduced in the two older age
      groups and most of all in women of very advanced age. Women of very advanced age
      had the lowest scores at all time points and this was most pronounced at three
      years after the birth. CONCLUSION: First-time mothers of advanced and very
      advanced age reported a slightly lower degree of satisfaction with life compared
      with the reference group of younger women, and the age-related effect was
      greatest when the child was three years of age.

PMID- 24564873
TI  - How women's sexual orientation guides accuracy of interpersonal judgements of
      other women.
AB  - This research examines how women's sexual orientation guides the accuracy of
      judgements of other women. One hundred ten judges (67 straight and 43 lesbian
      women) watched videotapes of 9 targets (4 straight and 5 lesbian) and made
      judgements about the targets' thoughts, emotions, personality, and sexual
      orientation. Accuracy scores were created for each judge by comparing judgements
      to criterion data gathered about targets. Straight judges were significantly more
      accurate at judging thoughts and marginally more accurate at judging emotions
      compared to lesbian judges. There were no significant differences in judging
      personality. Straight targets' thoughts and personality were more easily assessed
      than lesbian targets' while lesbians' emotions were more easily judged than
      straight targets'. Lesbian judges were more accurate at judging sexual
      orientation regardless of their tendency to categorize women as lesbian compared
      to straight judges. Findings support past research on the accurate perception of
      sexual orientation and contribute to understanding how sexual orientation guides
      person perception. 

PMID- 24564874
TI  - Ranking and compacting binding segments of protein families using aligned pattern
      clusters.
AB  - BACKGROUND: Discovering sequence patterns with variation can unveil functions of
      a protein family that are important for drug discovery. Exploring protein
      families using existing methods such as multiple sequence alignment is
      computationally expensive, thus pattern search, called motif finding in
      Bioinformatics, is used. However, at present, combinatorial algorithms result in
      large sets of solutions, and probabilistic models require a richer representation
      of the amino acid associations. To overcome these shortcomings, we present a
      method for ranking and compacting these solutions in a new representation
      referred to as Aligned Pattern Clusters (APCs). To tackle the problem of a large
      solution set, our method reveals a reduced set of candidate solutions without
      losing any information. To address the problem of representation, our method
      captures the amino acid associations and conservations of the aligned patterns.
      Our algorithm renders a set of APCs in which a set of patterns is discovered,
      pruned, aligned, and synthesized from the input sequences of a protein family.
      RESULTS: Our algorithm identifies the binding or other functional segments and
      their embedded residues which are important drug targets from the cytochrome c
      and the ubiquitin protein families taken from Unitprot. The results are
      independently confirmed by pFam's multiple sequence alignment. For cytochrome c
      protein the number of resulting patterns with variations are reduced by 76.62%
      from the number of original patterns without variations. Furthermore, all of the
      top four candidate APCs correspond to the binding segments with one of each of
      their conserved amino acid as the binding residue. The discovered proximal APCs
      agree with pFam and PROSITE results. Surprisingly, the distal binding site
      discovered by our algorithm is not discovered by pFam nor PROSITE, but confirmed
      by the three-dimensional cytochrome c structure. When applied to the ubiquitin
      protein family, our results agree with pFam and reveals six of the seven Lysine
      binding residues as conserved aligned columns with entropy redundancy measure of
      1.0. CONCLUSION: The discovery, ranking, reduction, and representation of a set
      of patterns is important to avert time-consuming and expensive simulations and
      experimentations during proteomic study and drug discovery.

PMID- 24564875
TI  - GeneTopics--interpretation of gene sets via literature-driven topic models.
AB  - BACKGROUND: Annotation of a set of genes is often accomplished through comparison
      to a library of labelled gene sets such as biological processes or canonical
      pathways. However, this approach might fail if the employed libraries are not up
      to date with the latest research, don't capture relevant biological themes or are
      curated at a different level of granularity than is required to appropriately
      analyze the input gene set. At the same time, the vast biomedical literature
      offers an unstructured repository of the latest research findings that can be
      tapped to provide thematic sub-groupings for any input gene set. METHODS: Our
      proposed method relies on a gene-specific text corpus and extracts commonalities
      between documents in an unsupervised manner using a topic model approach. We
      automatically determine the number of topics summarizing the corpus and calculate
      a gene relevancy score for each topic allowing us to eliminate non-specific
      topics. As a result we obtain a set of literature topics in which each topic is
      associated with a subset of the input genes providing directly interpretable
      keywords and corresponding documents for literature research. RESULTS: We
      validate our method based on labelled gene sets from the KEGG metabolic pathway
      collection and the genetic association database (GAD) and show that the approach
      is able to detect topics consistent with the labelled annotation. Furthermore, we
      discuss the results on three different types of experimentally derived gene sets,
      (1) differentially expressed genes from a cardiac hypertrophy experiment in mice,
      (2) altered transcript abundance in human pancreatic beta cells, and (3) genes
      implicated by GWA studies to be associated with metabolite levels in a healthy
      population. In all three cases, we are able to replicate findings from the
      original papers in a quick and semi-automated manner. CONCLUSIONS: Our approach
      provides a novel way of automatically generating meaningful annotations for gene
      sets that are directly tied to relevant articles in the literature. Extending a
      general topic model method, the approach introduced here establishes a workflow
      for the interpretation of gene sets generated from diverse experimental scenarios
      that can complement the classical approach of comparison to reference gene sets.

PMID- 24564876
TI  - Mild isoniazid-induced liver injury in humans is associated with an increase in
      Th17 cells and T cells producing IL-10.
AB  - Isoniazid (INH) remains a mainstay for the treatment of tuberculosis despite the
      fact that it can cause liver failure. The mechanism of INH-induced liver injury
      remains controversial. It had been proposed that the mechanism involves metabolic
      idiosyncrasy based on the observations that liver injury is not usually
      associated with fever, rash, or prompt increase in alanine aminotransferase (ALT)
      upon rechallenge. In the present study, we found that patients who were treated
      with INH because of a positive tuberculosis (TB) skin test and developed a small
      increase in ALT had an increase in Th17 cells as well as T cells that produce
      interleukin (IL)-10, which suggests stimulation of an adaptive immune response.
      Th17 cells are considered inflammatory and could be involved in causing the liver
      injury. IL-10 is considered anti-inflammatory and could be the reason that more
      serious liver injury did not occur. These changes were not observed in patients
      who did not have an increase in ALT. These are the first data to show a change in
      the T cell profile in patients with mild INH-induced liver injury; however, it is
      difficult to determine whether these changes were the cause or the result of the
      liver injury. Nevertheless, together with other studies, the data suggest that
      INH-induced liver injury is immune-mediated, with mild injury resulting in immune
      tolerance.

PMID- 24564878
TI  - Optimization of orange oil nanoemulsion formation by isothermal low-energy
      methods: influence of the oil phase, surfactant, and temperature.
AB  - Nanoemulsions are particularly suitable as a platform in the development of
      delivery systems for lipophilic functional agents. This study shows that
      transparent orange oil nanoemulsions can be fabricated using an isothermal low
      energy method (spontaneous emulsification), which offers the advantage of
      fabricating flavor oil delivery systems using rapid and simple processing
      operations. Orange oil nanoemulsions were formed spontaneously by titration of a
      mixture of orange oil, carrier oil [medium-chain triglyceride (MCT)], and non
      ionic surfactant (Tween) into an aqueous solution (5 mM citrate buffer at pH 3.5)
      with continuous stirring. The oil/emulsion ratio content was kept constant (10 wt
      %), while the surfactant/emulsion ratio (SER) was varied (2.5-20 wt %). Oil-phase
      composition (orange oil/MCT ratio), SER, and surfactant type all had an
      appreciable effect on nanoemulsion formation and stability. Transparent
      nanoemulsions could be formed under certain conditions: 20% surfactant (Tween 40,
      60, or 80) and 10% oil phase (4-6% orange oil + 6-4% MCT). Surfactant type and
      oil-phase composition also affected the thermal stability of the nanoemulsions.
      Most of the nanoemulsions broke down after thermal cycling (from 20 to 90 
      degrees C and back to 20  degrees C); however, one system remained transparent
      after thermal cycling: 20% Tween 80, 5% orange oil, and 5% MCT. The mean droplet
      size of these nanoemulsions increased over time, but the droplet growth rate was
      reduced appreciably after dilution. These results have important implications for
      the design and utilization of nanoemulsions as delivery systems in the food and
      other industries. 

PMID- 24564877
TI  - Decision aid for patients considering total knee arthroplasty with preference
      report for surgeons: a pilot randomized controlled trial.
AB  - BACKGROUND: To evaluate feasibility and potential effectiveness of a patient
      decision aid (PtDA) for patients and a preference report for surgeons to reduce
      wait times and improve decision quality in patients with osteoarthritis
      considering total knee replacement. METHODS: A prospective two-arm pilot
      randomized controlled trial. Patients with osteoarthritis were eligible if they
      understood English and were referred for surgical consultation about an initial
      total knee arthroplasty at a Canadian orthopaedic joint assessment clinic.
      Patients were randomized to the PtDA intervention or usual education. The
      intervention was an osteoarthritis PtDA for patients and a one-page preference
      report summarizing patients' clinical and decisional data for their surgeon. The
      main feasibility outcomes were rates of recruitment and questionnaire completion;
      the preliminary effectiveness outcomes were wait times and decision quality.
      RESULTS: Of 180 patients eligible for surgical consultation, 142 (79%) were
      recruited and randomized to the PtDA intervention (n = 71) or usual education (n
      = 71). Data collection yielded a 93% questionnaire completion rate with less than
      1% missing items. After one year, 13% of patients remained on the surgical wait
      list. The median time from referral to being off the wait list (censored using
      survival analysis techniques) was 33.4 weeks for the PtDA group (n = 69, 95% CI:
      26.0, 41.4) and 33.0 weeks for usual education (n = 71, 95% CI: 26.1, 39.9).
      Patients exposed to the PtDA had higher decision quality based on knowledge (71%
      versus 47%; p < 0.0001) and quality decision being an informed choice that is
      consistent with their values for option outcomes (56.4% versus 25.0%; p < 0.001).
      CONCLUSIONS: Recruitment of patients with osteoarthritis considering surgery and
      data collection were feasible. As some patients remained on the surgical waiting
      list after one year, follow-up should be extended to two years. Patients exposed
      to the PtDA achieved higher decision quality compared to those receiving usual
      education but there was no difference in wait for surgery. TRIALS REGISTRATION:
      ClinicalTrials.Gov NCT00743951.

PMID- 24564879
TI  - Implanted functional electrical stimulation: case report of a paraplegic patient
      with complete SCI after 9 years.
AB  - BACKGROUNDS: Experience of an implanted functional electrical stimulation
      neuroprosthesis (FES) associating 8-channel epimysial and 4-channel neural
      stimulations. The primary objective consisted in presenting clinical and
      technological experiences based on a 9-year follow-up of one patient implanted
      with this FES device. The secondary objective consisted in assessing resulting
      functional benefits. METHODS: One patient recruited in 1996 within the European
      Stand Up and Walk Project benefited from a 9-year follow-up with clinical and
      technological evaluations. RESULTS: The patient was still using the system nine
      years later making this a unique case, even when compared to other similar
      studies. The analysis of muscular response to FES underlined the great
      variability of stimulation thresholds evolution (-26% to +360%, mean +110%) and
      quality of the induced contraction. Three muscles out of five scored at least 4/5
      on the Medical Research Council scale, all stimulated via neural pathways. The
      patient used the system once a week for 6 years, up to 2006, due to lack of use,
      the FES-induced muscular response worsened even though the implant was properly
      functioning, leading to significant decline in gait performances (best 3.45 m/s
      on 2.9 m), due to muscle fatigue and loss of muscle mass. CONCLUSION: Two major
      issues arise: first the importance of muscle fatigue, underlining the relevance
      of muscle strength training, and second technological hurdles raising up the
      question of neural vs. epimysial FES. This advanced technology proves the concept
      of restoring lower limb motor functions in patients with spinal cord injury. The
      main features of the stimulation device remain stable even after long periods of
      inactivity, yet there is a real need for close clinical and technological
      monitoring.

PMID- 24564880
TI  - Plastic and elastic strain fields in GaAs/Si core-shell nanowires.
AB  - Thanks to their unique morphology, nanowires have enabled integration of
      materials in a way that was not possible before with thin film technology. In
      turn, this opens new avenues for applications in the areas of energy harvesting,
      electronics, and optoelectronics. This is particularly true for axial
      heterostructures, while core-shell systems are limited by the appearance of
      strain-induced dislocations. Even more challenging is the detection and
      understanding of these defects. We combine geometrical phase analysis with finite
      element strain simulations to quantify and determine the origin of the lattice
      distortion in core-shell nanowire structures. Such combination provides a
      powerful insight in the origin and characteristics of edge dislocations in such
      systems and quantifies their impact with the strain field map. We apply the
      method to heterostructures presenting single and mixed crystalline phase. Mixing
      crystalline phases along a nanowire turns out to be beneficial for reducing
      strain in mismatched core-shell structures. 

PMID- 24564882
TI  - Metabolic syndrome for sub-Saharan Africans diabetes with peripheral arterial
      disease: a case-control study.
AB  - BACKGROUND: Currently, there is no value for the definition of abdominal obesity
      by measuring waist circumference in the Sub-Saharan Africa. Several definitions
      of metabolic syndrome (MS) have disparities concerning use of waist
      circumference, including International Diabetes Federation (IDF), American Heart
      Association/National Heart, Lung and Blood Institute (AHA/NHLBI) and National
      Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATPIII)
      definitions. The aim of the study was to determine what value of waist
      circumference should be used and whether to use it as obligatory criterion in the
      metabolic syndrome in case of peripheral arterial disease (PAD). METHODS: We
      conducted a case-control study in Cameroon. We included patients with diabetic
      foot and type 2 diabetes and excluded those with an Ankle Brachial Index (ABI) >
      1.3. Cases were defined as patients with ABI <= 0.9 and controls with ABI > 0.9.
      The significant p value was < 0.05 and odds ratio (OR) with 95% confidence
      interval was used to measured risk for have PAD with MS. RESULTS: We included 19
      cases and 48 controls. The risk for having PAD with MS are for the IDF: OR = 4.7
      (1.4-15.1), p = 0.008, for the AHA/NHLBI: OR = 5.8 (1.5-22.5), p = 0.007, for the
      NCEP-ATPIII: OR = 1.8 (0.6-5.6), p = 0.286. CONCLUSION: Abdominal obesity should
      be defined according to the recommendations of the IDF and AHA/NHLBI and should
      not be an obligatory criterion in the definition of MS for research risk to have
      PAD on sub-Saharan Africa.

PMID- 24564881
TI  - Magnetic field-induced T cell receptor clustering by nanoparticles enhances T
      cell activation and stimulates antitumor activity.
AB  - Iron-dextran nanoparticles functionalized with T cell activating proteins have
      been used to study T cell receptor (TCR) signaling. However, nanoparticle
      triggering of membrane receptors is poorly understood and may be sensitive to
      physiologically regulated changes in TCR clustering that occur after T cell
      activation. Nano-aAPC bound 2-fold more TCR on activated T cells, which have
      clustered TCR, than on naive T cells, resulting in a lower threshold for
      activation. To enhance T cell activation, a magnetic field was used to drive
      aggregation of paramagnetic nano-aAPC, resulting in a doubling of TCR cluster
      size and increased T cell expansion in vitro and after adoptive transfer in vivo.
      T cells activated by nano-aAPC in a magnetic field inhibited growth of B16
      melanoma, showing that this novel approach, using magnetic field-enhanced nano
      aAPC stimulation, can generate large numbers of activated antigen-specific T
      cells and has clinically relevant applications for adoptive immunotherapy. 

PMID- 24564883
TI  - Cost-effectiveness analysis of vaccinating children in Malawi with RTS,S vaccines
      in comparison with long-lasting insecticide-treated nets.
AB  - BACKGROUND: New RTS,S malaria vaccines may soon be licensed, yet its cost
      effectiveness is unknown. Before the widespread introduction of RTS,S vaccines,
      cost-effectiveness studies are needed to help inform governments in resource-poor
      settings about how best to prioritize between the new vaccine and existing
      malaria interventions. METHODS: A Markov model simulated malaria progression in a
      hypothetical Malawian birth cohort. Parameters were based on published data.
      Three strategies were compared: no intervention, vaccination at one year, and
      long-lasting, insecticide-treated nets (LLINs) at birth. Both health service and
      societal perspectives were explored. Health outcomes were measured in disability
      adjusted life years (DALYs) averted and costed in 2012 US$. Incremental cost
      effectiveness ratios (ICERs) were calculated and extensive sensitivity analyses
      were conducted. Three times GDP per capita ($1,095) per DALY averted was used for
      a cost-effectiveness threshold, whilst one times GDP ($365) was considered 'very
      cost-effective'. RESULTS: From a societal perspective the vaccine strategy was
      dominant. It averted 0.11 more DALYs than LLINs and 0.372 more DALYs than the no
      intervention strategy per person, while costing $10.04 less than LLINs and $59.74
      less than no intervention. From a health service perspective the vaccine's ICER
      was $145.03 per DALY averted, and thus can be considered very cost-effective. The
      results were robust to changes in all variables except the vaccine and LLINs'
      duration of efficacy. Vaccines remained cost-effective even at the lowest assumed
      efficacy levels of 49.6% (mild malaria) and 14.2% (severe malaria), and the
      highest price of $15. However, from a societal perspective, if the vaccine
      duration efficacy was set below 2.69 years or the LLIN duration of efficacy was
      greater than 4.24 years then LLINs became the more cost-effective strategy.
      CONCLUSION: The results showed that vaccinating Malawian children with RTS,S
      vaccines was very cost-effective from both a societal and a health service
      perspective. This result was robust to changes in most variables, including
      vaccine price and vaccine efficacy, but was sensitive to the duration of efficacy
      of the vaccine and LLINs. Given the best evidence currently available, vaccines
      can be considered as a very cost-effective component of Malawi's future malaria
      control programmes. However, long-term follow-up studies on both interventions
      are needed.

PMID- 24564884
TI  - Conceptualization of molecular findings by mining gene annotations.
AB  - BACKGROUND: The Gene Ontology (GO) is an ontology representing molecular biology
      concepts related to genes and their products. Current annotations from the GO
      Consortium tend to be highly specific, and contemporary genome-scale studies
      often return a long list of genes of potential interest, such as genes in a
      cancer tumor that are differentially expressed than those found in normal tissue.
      It is therefore a challenging task to reveal, at a conceptual level, the major
      functional themes in which genes are involved. Presently, there is a need for
      tools capable of revealing such themes through mining and representing semantic
      information in an objective and quantitative manner. METHODS: In this study, we
      utilized the hierarchical organization of the GO to derive a more abstract
      representation of the major biological processes of a list of genes based on
      their annotations. We cast the task as follows: given a list of genes, identify
      non-disjoint, functionally coherent subsets, such that the functions of the genes
      in a subset are summarized by an informative GO term that accurately captures the
      semantic information of the original annotations. RESULTS: We evaluated different
      metrics for assessing information loss when merging GO terms, and different
      statistical schemes to assess the functional coherence of a set of genes. We
      found that the best discriminative power was achieved by using a combination of
      the information-content-based measure as the information-loss metric, and the
      graph-based statistics derived from a Steiner tree connecting genes in an
      augmented GO graph. CONCLUSIONS: Our methods provide an objective and
      quantitative approach to capturing the major directions of gene functions in a
      context-specific fashion.

PMID- 24564887
TI  - Fully automated protein complex prediction based on topological similarity and
      community structure.
AB  - To understand the function of protein complexes and their association with
      biological processes, a lot of studies have been done towards analyzing the
      protein-protein interaction (PPI) networks. However, the advancement in high
      throughput technology has resulted in a humongous amount of data for analysis.
      Moreover, high level of noise, sparseness, and skewness in degree distribution of
      PPI networks limits the performance of many clustering algorithms and further
      analysis of their interactions. 

PMID- 24564886
TI  - Characterizing dynamic regulatory programs in mouse lung development and their
      potential association with tumourigenesis via miRNA-TF-mRNA circuits.
AB  - BACKGROUND: In dynamic biological processes, genes, transcription factors(TF) and
      microRNAs(miRNAs) play vital regulation roles. Many researchers have focused on
      the transcription factors or miRNAs in transcriptional or post transcriptional
      stage, respectively. However, the transcriptional regulation and post
      transcriptional regulation is not isolated in the whole dynamic biological
      processes, there are few reserchers who have tried to consider the network
      composed by genes, miRNAs and TFs in this dynamic biological processes,
      especially in the mouse lung development. Moreover, it is widely acknowledged
      that cancer is a kind of developmental disorders, and some of pathways involved
      in tissue development might be also implicated in causing cancer. Although it has
      been found that many genes differentially expressed during mouse lung development
      are also differentially expressed in lung cancer, very little work has been
      reported to elucidate the combinational regulatory programs of such kind of
      associations. RESULTS: In order to investigate the association of transcriptional
      and post-transcriptional regulating activities in the mouse lung development, we
      define the significant triple relations among miRNAs, TFs and mRNAs as circuits.
      From the lung development time course data GSE21053, we mine 142610 circuit
      candidates including 96 TFs, 129 miRNAs and 13403 genes. After removing genes
      with little variation along different time points, we finally find 64760 circuit
      candidates, containing 8299 genes, 50 TFs, and 118 miRNAs in total. Further
      analysis on the circuits shows that the circuits vary in different stages of the
      lung development and play different roles. By investigating the circuits in the
      context of lung specific genes, we identify out the regulatory combinations for
      lung specific genes, as well as for those lung non-specific genes. Moreover, we
      show that the lung non-specific genes involved circuits are functionally related
      to the lung development. Noticing that some tissue developmental systems may be
      involved in tumourigenesis, we also check the cancer genes involved circuits,
      trying to find out their regulatory program, which would be useful for the
      research of lung cancer. CONCLUSIONS: The relevant transcriptional or post
      transcriptional factors and their roles involved in the mouse lung development
      are both changed greatly in different stages. By investigating the cancer genes
      involved circuits, we can find miRNAs/TFs playing important roles in tumour
      progression. Therefore, the miRNA-TF-mRNA circuits can be used in wide
      translational biomedicine studies, and can provide potential drug targets towards
      the treatment of lung cancer.

PMID- 24564885
TI  - Neurovascular unit on a chip: implications for translational applications.
AB  - The blood-brain barrier (BBB) dynamically controls exchange between the brain and
      the body, but this interaction cannot be studied directly in the intact human
      brain or sufficiently represented by animal models. Most existing in vitro BBB
      models do not include neurons and glia with other BBB elements and do not
      adequately predict drug efficacy and toxicity. Under the National Institutes of
      Health Microtissue Initiative, we are developing a three-dimensional,
      multicompartment, organotypic microphysiological system representative of a
      neurovascular unit of the brain. The neurovascular unit system will serve as a
      model to study interactions between the central nervous system neurons and the
      cerebral spinal fluid (CSF) compartment, all coupled to a realistic blood
      surrogate supply and venous return system that also incorporates circulating
      immune cells and the choroid plexus. Hence all three critical brain barriers will
      be recapitulated: blood-brain, brain-CSF, and blood-CSF. Primary and stem cell
      derived human cells will interact with a variety of agents to produce critical
      chemical communications across the BBB and between brain regions.
      Cytomegalovirus, a common herpesvirus, will be used as an initial model of
      infections regulated by the BBB. This novel technological platform, which
      combines innovative microfluidics, cell culture, analytical instruments,
      bioinformatics, control theory, neuroscience, and drug discovery, will replicate
      chemical communication, molecular trafficking, and inflammation in the brain. The
      platform will enable targeted and clinically relevant nutritional and
      pharmacologic interventions for or prevention of such chronic diseases as obesity
      and acute injury such as stroke, and will uncover potential adverse effects of
      drugs. If successful, this project will produce clinically useful technologies
      and reveal new insights into how the brain receives, modifies, and is affected by
      drugs, other neurotropic agents, and diseases. 

PMID- 24564889
TI  - The effects of cichorium intybus extract on the maturation and activity of
      dendritic cells.
AB  - BACKGROUND: Cichorium intybus is a medicinal plant commonly used in traditional
      medicine for its benefits in immune-madiated disorders. There are several
      evidences showing that C. intybus can modulate immune responses. In the present
      study we have investigated the effects of the ethanolic root extract of this
      plant on the immune system by targeting dendritic cells (DCs). For this purpose,
      phenotypic and functional maturity of murine DCs after treatment with the extract
      was analyzed by flow cytometry and mixed lymphocyte reaction (MLR) assay.
      RESULTS: C. intybus did not change the expression of CD40, CD86 and MHC-II
      molecules as important co-stimulatory markers on DCs compared to the control,
      indicating that it could not promote DCs phenotypic maturation. Treatment of DCs
      with lower concentrations of the extract resulted in an increased production of
      IL-12 by these cells with no change in IL-10 release. The capacity of treated DCs
      to stimulate allogenic T cells proliferation and cytokines secretion was examined
      in the co-cuture of these cells with T cells in MLR. C. intybus at higher
      concentrations inhibited proliferation of allogenic T cells and in lower
      concentrations changed the level of cytokines such that IL-4 decreased and IFN
      gamma increased. CONCLUSIONS: These results indicated that C. intybus extract at
      higher concentrations can inhibit T cell stimulating activity of DCs, whereas at
      lower concentrations can modulate cytokine secretion toward a Th1 pattern. These
      data may in part explain the traditional use of this plant in treatment of immune
      mediated disorders.

PMID- 24564888
TI  - Wnt modulates MCL1 to control cell survival in triple negative breast cancer.
AB  - BACKGROUND: Triple negative breast cancer (TNBC) has higher rates of recurrence
      and distant metastasis, and poorer outcome as compared to non-TNBC. Aberrant
      activation of WNT signaling has been detected in TNBC, which might be important
      for triggering oncogenic conversion of breast epithelial cell. Therefore, we
      directed our focus on identifying the WNT ligand and its underlying mechanism in
      TNBC cells. METHODS: We performed large-scale analysis of public microarray data
      to screen the WNT ligands and the clinical significance of the responsible ligand
      in TNBC. WNT5B was identified and its overexpression in TNBC was confirmed by
      immunohistochemistry staining, Western blot and ELISA. ShRNA was used to
      knockdown WNT5B expression (shWNT5B). Cellular functional alteration with shWNT5B
      treatment was determined by using wound healing assay, mammosphere assay; while
      cell cycle and apoptosis were examined by flowcytometry. Mitochondrial morphology
      was photographed by electron microscope. Biological change of mitochondria was
      detected by RT-PCR and oxygen consumption assay. Activation of WNT pathway and
      its downstream targets were evaluated by liciferase assay, immunohistochemistry
      staining and immunoblot analysis. Statistical methods used in the experiments
      besides microarray analysis was two-tailed t-test. RESULTS: WNT5B was elevated
      both in the tumor and the patients' serum. Suppression of WNT5B remarkably
      impaired cell growth, migration and mammosphere formation. Additionally, G0/G1
      cell cycle arrest and caspase-independent apoptosis was observed. Study of the
      possible mechanism indicated that these effects occurred through suppression of
      mitochondrial biogenesis, as evidenced by reduced mitochondrial DNA (MtDNA) and
      compromised oxidative phosphorylation (OXPHOS). In Vivo and in vitro data
      uncovered that WNT5B modulated mitochondrial physiology was mediated by MCL1,
      which was regulated by WNT/beta-catenin responsive gene, Myc. Clinic data
      analysis revealed that both WNT5B and MCL1 are associated with enhanced
      metastasis and decreased disease-free survival. CONCLUSIONS: All our findings
      suggested that WNT5B/MCL1 cascade is critical for TNBC and understanding its
      regulatory apparatus provided valuable insight into the pathogenesis of the tumor
      development and the guidance for targeting therapeutics.

PMID- 24564890
TI  - Viewpoint discrimination and contestation of ideas on its merits, leadership and
      organizational ethics: expanding the African bioethics agenda.
AB  - The 3rd Pan-African Ethics Human Rights and Medical Law (3rd EHRML) conference
      was held in Johannesburg on July 7, 2013, as part of the Africa Health Congress.
      The conference brought together bioethicists, researchers and scholars from South
      Africa, Zimbabwe, Kenya and Nigeria working in the field of bioethics as well as
      students and healthcare workers interested in learning about ethical issues
      confronting the African continent. The conference which ran with a theme of
      "Bioethical and legal perspectives in biomedical research and medical practice in
      Africa with a focus on: Informed consent, HIV-AIDS & Tuberculosis, leadership &
      organizational ethics, patients and healthcare workers rights," was designed to
      expand the dialogue on African bioethics beyond the traditional focus on research
      ethics and the ethical dilemmas surrounding the conduct of biomedical research in
      developing countries. This introductory article highlights some of areas of focus
      at the conference including issues of leadership, organizational ethics and
      patients and healthcare workers rights in Africa. We analyze the importance of
      free speech, public debate of issues, argumentation and the need to introduce the
      teaching and learning of ethics to students in Africa in accordance with UNESCO
      guidelines. This article also focuses on other challenges confronting Africa
      today from an ethical standpoint, including the issues of poor leadership and
      organizational ethics which are main contributors to the problems prevalent in
      African countries, such as poverty, poor education and healthcare delivery
      systems, terrorism, social inequities, infrastructural deficits and other forms
      of 'structural violence' confronting vulnerable African communities. We believe
      that each of the eight articles included in this supplement, which have been
      rigorously peer-reviewed are a good example of current research on bioethics in
      Africa, and explore some new directions towards broadening the African bioethics
      agenda as we move forward to a new dawn for Africa in the 21st century.

PMID- 24564891
TI  - Characterization of the nonlinear optical properties of nanocrystals by Hyper
      Rayleigh Scattering.
AB  - BACKGROUND: Harmonic Nanoparticles are a new family of exogenous markers for
      multiphoton imaging exerting optical contrast by second harmonic (SH) generation.
      In this tutorial, we present the application of Hyper-Rayleigh Scattering (HRS)
      for a quantitative assessment of the nonlinear optical properties of these
      particles and discuss the underlying theory and some crucial experimental
      aspects. METHODS: The second harmonic properties of BaTiO3, KNbO3, KiTiOPO4
      (KTP), LiNbO3 and ZnO nanocrystals (NCs) are investigated by HRS measurements
      after careful preparation and characterization of colloidal suspensions. RESULTS:
      A detailed analysis of the experimental results is presented with emphasis on the
      theoretical background and on the influence of some experimental parameters
      including the accurate determination of the nanocrystal size and concentration.
      The SH generation efficiency and averaged nonlinear optical coefficients are then
      derived and compared for six different types of NCs. CONCLUSIONS: After
      preparation of colloidal NC suspensions and careful examination of their size,
      concentration and possible aggregation state, HRS appears as a valuable tool to
      quantitatively assess the SH efficiency of noncentrosymmetric NCs. All the
      investigated nanomaterials show high SH conversion efficiencies, demonstrating a
      good potential for bio-labelling applications.

PMID- 24564893
TI  - The 6th Computational Structural Bioinformatics Workshop.
AB  - INTRODUCTION: The rapid accumulation of macromolecular structures presents a
      unique set of challenges and opportunities in the analysis, comparison, modeling,
      and prediction of macromolecular structures and interactions. The 6th
      Computational Structural Bioinformatics Workshop (CSBW) was held in Philadelphia
      on October 4, 2012. This issue includes eleven papers selected from the work
      presented at the CSBW of 2012. In "Four-body atomic potential for modeling
      protein-ligand binding affinity: application to enzyme-inhibitor binding energy
      prediction", a predictive model of free-energy was built to evaluate the binding
      between a protein and a ligand. In "Unbiased, scalable sampling of protein loop
      conformations from probabilistic priors", a new Markov chain Monte Carlo
      algorithm was proposed to generate unbiased conformations of closed protein loops
      from probabilistic priors. In "Enhancement of accuracy and efficiency for RNA
      secondary structure prediction by sequence segmentation and MapReduce", authors
      demonstrate an enhanced method by cutting a long RNA sequence into smaller chunks
      at strategically selected points, and distributing the tasks to multiple
      processors. In "A population-based evolutionary search approach to the multiple
      minima problem in de novo protein structure prediction", the authors present an
      evolutionary search algorithm to obtain a discrete representation of the protein
      energy surface in terms of an ensemble of conformations representing local energy
      minima. In "Estimating loop length from Cryo-EM images at medium resolutions",
      the authors developed a computational geometry method to simplify the points
      along the skeleton to measure loop length in 3D images. The paper "A conservation
      and rigidity based method for detecting critical protein residues" presents a
      method that combines the rigidity and the evolutionary conservation in detection
      of the critical residues. In "A conservation and biophysics guided stochastic
      approach to refining docked multimeric proteins", the authors introduce a
      refinement method that accepts complexes consisting of any number of monomeric
      units. In "Elucidating the ensemble of functionally-relevant transitions in
      protein systems with a robotics-inspired method," the authors present a robotics
      inspired tree-based method to sample energetically-credible conformational
      pathways connecting diverse functional states in multimodal proteins. The paper
      "An aggregate analysis of many predicted structures to reduce errors in protein
      structure comparison caused by conformational flexibility" applies protein
      structure prediction algorithms to enhance the classification of homologous
      proteins according to their binding preferences. In "DINC: A new AutoDock-based
      protocol for docking large ligands", an enhanced method was demonstrated for
      docking large ligands. The paper "Modeling protein conformational transitions by
      a combination of coarse-grained normal mode analysis and robotics-inspired
      methods" presents an efficient approach involving robotics concepts.

PMID- 24564892
TI  - Viral aetiology influenza like illnesses in Santa Cruz, Bolivia (2010-2012).
AB  - BACKGROUND: Acute respiratory infections represent a serious public health issue
      worldwide but virological aetiologies of Influenza Like Illnesses (ILIs) remain
      largely unknown in developing countries. This study represents the first attempt
      to characterise viral aetiologies of ILIs in Bolivia. METHODS: It was performed
      in Santa Cruz city from January 2010 to September 2012, based on 564 naso
      pharyngeal swabs collected in a National Reference Laboratory and real-time PCR
      techniques, viral cultures and phylogenetic analyses. RESULTS: 50.2% of samples
      were positive for at least one virus with influenza viruses (Flu A: ~15%; Flu B:
      ~9%), rhinoviruses (~8%), coronaviruses (~5%) and hRSV (~4%) being the most
      frequently identified. The pattern of viral infections varied according to age
      groups. The elucidation rate was the highest (>60%) amongst patients under 10 yo
      and the lowest (<40%) amongst patients >=60 yo. Nearly 3% of samples showed dual
      viral infections. Epidemiological peaks were associated with a predominant virus
      but generally included 30-50% of infections by different viruses. Unexpectedly,
      the frequency of influenza in the 0-4 yo population was very low and a complete
      hRSV eclipse occurred in 2011. Genetic analyses indicated that distinct
      evolutionary lineages of Flu A(H1N1)pdm2009, Flu A/H3N2 and Flu B have co
      circulated in Bolivia in the study period, originating from Central and North
      America, Europe, Asia and Australia. CONCLUSION: Our results emphasise the
      requirement for a reinforced epidemiological and genetic follow-up of influenza
      and other ILIs in Bolivia to further inform the preparation of vaccines used in
      the region, guide vaccination campaigns and improve the medical management of
      patients.

PMID- 24564894
TI  - An accountability framework to promote healthy food environments.
AB  - OBJECTIVE: To review the available literature on accountability frameworks to
      construct a framework that is relevant to voluntary partnerships between
      government and food industry stakeholders. DESIGN: Between November 2012 and May
      2013, a desk review of ten databases was conducted to identify principles,
      conceptual frameworks, underlying theories, and strengths and limitations of
      existing accountability frameworks for institutional performance to construct a
      new framework relevant to promoting healthy food environments. SETTING: Food
      policy contexts within high-income countries to address obesity and diet-related
      non-communicable diseases. SUBJECTS: Eligible resources (n 26) were reviewed and
      the guiding principles of fifteen interdisciplinary frameworks were used to
      construct a new accountability framework. RESULTS: Strengths included shared
      principles across existing frameworks, such as trust, inclusivity, transparency
      and verification; government leadership and good governance; public
      deliberations; independent bodies recognizing compliance and performance
      achievements; remedial actions to improve accountability systems; and capacity to
      manage conflicts of interest and settle disputes. Limitations of the three-step
      frameworks and 'mutual accountability' approach were an explicit absence of an
      empowered authority to hold all stakeholders to account for their performance.
      CONCLUSIONS: We propose a four-step accountability framework to guide government
      and food industry engagement to address unhealthy food environments as part of a
      broader government-led strategy to address obesity and diet-related non
      communicable diseases. An independent body develops clear objectives, a
      governance process and performance standards for all stakeholders to address
      unhealthy food environments. The empowered body takes account (assessment),
      shares the account (communication), holds to account (enforcement) and responds
      to the account (improvements).

PMID- 24564895
TI  - A new role for penicillin acylases: degradation of acyl homoserine lactone quorum
      sensing signals by Kluyvera citrophila penicillin G acylase.
AB  - Use of penicillin acylases for the production of semi-synthetic penicillins is
      well-known. Escherichia coli penicillin G acylase (EcPGA) has been extensively
      used for this purpose; however, Kluyvera citrophila penicillin G acylase (KcPGA)
      is assumed to be a better substitute, owing to its increased resilience to
      extreme pH conditions and ease of immobilization. In the present article we
      report a new dimension for the amidase activity of KcPGA by demonstrating its
      ability to cleave bacterial quorum sensing signal molecules, acyl homoserine
      lactones (AHL) with acyl chain length of 6-8 with or without oxo-substitution at
      third carbon position. Initial evidence of AHL degrading capability of KcPGA was
      obtained using CV026 based bioassay method. Kinetic studies performed at pH 8.0
      and 50  degrees C revealed 3-oxo-C6 HSL to be the best substrate for the enzyme
      with V(max) and K(m) values of 21.37+0.85 mM/h/mg of protein and 0.1+0.01 mM,
      respectively. C6 HSL was found to be the second best substrate with V(max) and
      K(m) value of 10.06+0.27 mM/h/mg of protein and 0.28+0.02 mM, respectively.
      Molecular modeling and docking studies performed on the active site of the enzyme
      support these findings by showing the fitting of AHLs perfectly within the
      hydrophobic pocket of the enzyme active site.

PMID- 24564898
TI  - Proteomic analysis of sulfur-nitrogen-carbon removal by Pseudomonas sp. C27 under
      micro-aeration condition.
AB  - Pseudomonas sp. C27 is a facultative autotrophic bacterium (FAB) that can
      effectively conduct mixotrophic and heterotrophic denitrifying sulfide removal
      (DSR) reactions under anaerobic condition using organic matters and sulfide as
      electron donors. Micro-aeration was proposed to enhance DSR reaction by FAB;
      however, there is no experimental proof on the effects of micro-aeration on
      capacity of denitrifying sulfide removal of FAB on proteomic levels. The proteome
      in total C27 cell extracts was observed by two-dimensional gel electrophoresis.
      Differentially expressed protein spots and specifically expressed protein spots
      were identified by MALDI TOF/TOF MS. We identified 55 microaerobic-responsive
      protein spots, representing 55 unique proteins. Hierarchical clustering analysis
      revealed that 75% of the proteins were up-regulated, and 5% of the proteins were
      specifically expressed under micro-aerobic conditions. These enzymes were mainly
      involved in membrane transport, protein folding and metabolism. The noted
      expression changes of the microaerobic-responsive proteins suggests that C27
      strain has a highly efficient enzyme system to conduct DSR reactions under micro
      aerobic condition. Additionally, micro-aeration can increase the rates of protein
      synthesis and cell growth, and enhance cell defensive system of the strain. 

PMID- 24564897
TI  - Effect of surface charge alteration on stability of L-asparaginase II from
      Escherichia sp.
AB  - Escherichia coli L-asparaginases have great significance in the treatment of
      leukemia. Consequently, there is considerable interest in engineering this enzyme
      for improving its stability. In this work, the effect of surface charge on the
      stability of the enzyme l-asparaginase II was studied by site-directed
      mutagenesis of the cloned ansB gene from Escherichia sp. Replacement of two
      positively charged residues (K139 and K207) on the surface loops with neutral and
      reverse charges resulted in altered thermo stability in designed variants.
      Neutral charge substitutions (K139A and K207A) retained greater tolerance and
      stability followed by negative charge substitutions (K139D and K207D) compared to
      control mutant K139R and wild enzyme. From the results, it was concluded that the
      optimization of surface charge contributed much to the thermal properties of
      proteins without affecting the structure.

PMID- 24564896
TI  - Co-expression of phosphoenolpyruvate carboxykinase and nicotinic acid
      phosphoribosyltransferase for succinate production in engineered Escherichia
      coli.
AB  - Succinate is not the dominant fermentation product from xylose in wild-type
      Escherichia coli K12. E. coli BA 203 is a lactate dehydrogenase (ldhA), pyruvate
      formate lyase (pflB), and phosphoenolpyruvate (PEP)-carboxylase (ppc) deletion
      strain. To increase succinate accumulation and reduce byproduct formation,
      engineered E. coli BA204, in which ATP-forming PEP-carboxykinase (PEPCK) is
      overexpressed in BA203, was constructed and produced 2.17-fold higher succinate
      yield. To further improve the biomass and the consumption rate of xylose,
      nicotinic acid phosphoribosyltransferase (NAPRTase), a rate limiting enzyme in
      the synthesis of NAD(H), was also overexpressed. Thus, co-expression of PEPCK and
      NAPRTase in recombinant E. coli BA209 was investigated. In BA209, the pck gene
      and the pncB gene each have a trc promoter, hence, both genes are well expressed.
      During a 72-h anaerobic fermentation in sealed bottles, the total concentration
      of NAD(H) in BA209 was 1.25-fold higher than that in BA204, and the NADH/NAD+
      ratio decreased from 0.28 to 0.11. During the exclusively anaerobic fermentation
      in a 3-L bioreactor, BA209 consumed 17.1 g L-1 xylose and produced 15.5 g L-1
      succinate. Furthermore, anaerobic fermentation of corn stalk hydrolysate
      contained 30.1 g L-1 xylose, 2.1 g L-1 glucose and 1.5 g L-1 arabinose, it
      produced a final succinate concentration of 17.2 g L-1 with a yield of 0.94 g g-1
      total sugars.

PMID- 24564899
TI  - An amperometric biosensor based on horseradish peroxidase immobilized onto maize
      tassel-multi-walled carbon nanotubes modified glassy carbon electrode for
      determination of heavy metal ions in aqueous solution.
AB  - A biosensor for trace metal ions based on horseradish peroxidase (HRP)
      immobilized on maize tassel-multiwalled carbon nanotube (MT-MWCNT) through
      electrostatic interactions is described herein. The biosensor was characterized
      using Fourier transform infrared (FTIR), UV-vis spectrometry, voltammetric and
      amperometric methods. The FTIR and UV-vis results inferred that HRP was not
      denatured during its immobilization on MT-MWCNT composite. The biosensing
      principle was based on the determination of the cathodic responses of the
      immobilized HRP to H2O2, before and after incubation in trace metal standard
      solutions. Under optimum conditions, the inhibition rates of trace metals were
      proportional to their concentrations in the range of 0.092-0.55 mg L-1, 0.068-2
      mg L-1 for Pb2+ and Cu2+ respectively. The limits of detection were 2.5 MUg L-1
      for Pb2+ and 4.2 MUg L-1 for Cu2+. Representative Dixon and Cornish-Bowden plots
      were used to deduce the mode of inhibition induced by the trace metal ions. The
      inhibition was reversible and mixed for both metal ions. Furthermore, the
      biosensor showed good stability, selectivity, repeatability and reproducibility.

PMID- 24564900
TI  - Effects of gas periodic stimulation on key enzyme activity in gas double-dynamic
      solid state fermentation (GDD-SSF).
AB  - The heat and mass transfer have been proved to be the important factors in air
      pressure pulsation for cellulase production. However, as process of enzyme
      secretion, the cellulase formation has not been studied in the view of
      microorganism metabolism and metabolic key enzyme activity under air pressure
      pulsation condition. Two fermentation methods in ATPase activity, cellulase
      productivity, weight lose rate and membrane permeability were systematically
      compared. Results indicated that gas double-dynamic solid state fermentation had
      no obviously effect on cell membrane permeability. However, the relation between
      ATPase activity and weight loss rate was linearly dependent with r=0.9784.
      Meanwhile, the results also implied that gas periodic stimulation had apparently
      strengthened microbial metabolism through increasing ATPase activity during gas
      double-dynamic solid state fermentation, resulting in motivating the production
      of cellulase by Trichoderma reesei YG3. Therefore, the increase of ATPase
      activity would be another crucial factor to strengthen fermentation process for
      cellulase production under gas double-dynamic solid state fermentation. 

PMID- 24564901
TI  - An ene reductase from Clavispora lusitaniae for asymmetric reduction of activated
      alkenes.
AB  - A putative ene reductase gene from Clavispora lusitaniae was heterologously
      overexpressed in Escherichia coli, and the encoded protein (ClER) was purified
      and characterized for its biocatalytic properties. This NADPH-dependent
      flavoprotein was identified with reduction activities toward a diverse range of
      activated alkenes including conjugated enones, enals, maleimide derivative and
      alpha,beta-unsaturated carboxylic esters. The purified ClER exhibited a
      relatively high activity of 7.3 U mg(prot)-1 for ketoisophorone while a
      remarkable catalytic efficiency (k(cat)/K(m)=810 s-1 mM-1) was obtained for 2
      methyl-cinnamaldehyde due to the high affinity. A series of prochiral activated
      alkenes were stereoselectively reduced by ClER furnishing the corresponding
      saturated products in up to 99% ee. The practical applicability of ClER was
      further evaluated for the production of (R)-levodione, a valuable chiral
      compound, from ketoisophorone. Using the crude enzyme of ClER and glucose
      dehydrogenase (GDH), 500 mM of ketoisophorone was efficiently converted to (R)
      levodione with excellent stereoselectivity (98% ee) within 1h. All these positive
      features demonstrate a high synthetic potential of ClER in the asymmetric
      reduction of activated alkenes.

PMID- 24564902
TI  - Characterization and site-directed mutagenesis of an alpha-galactosidase from the
      deep-sea bacterium Bacillus megaterium.
AB  - A novel gene (BmelA) (1323bp) encoding an alpha-galactosidase of 440 amino acids
      was cloned from the deep-sea bacterium Bacillus megaterium and the protein was
      expressed in Escherichia coli BL21 (DE3) with an estimated molecular mass of
      about 45 kDa by SDS-PAGE. The enzyme belongs to glycoside hydrolase family 4,
      with the highest identity (74%) to alpha-galactosidase Mel4A from Bacillus
      halodurans among the characterized alpha-galactosidases. The recombinant BmelA
      displayed its maximum activity at 35  degrees C and pH 8.5-9.0 in 50 mM Tris-HCl
      buffer, and could hydrolyze different substrates with the Km values against p
      nitrophenyl-alpha-D-galactopyranoside (pNP-alpha-Gal), raffinose and stachyose
      being 1.02+/-0.02, 2.24+/-0.11 and 3.42+/-0.17 mM, respectively. Besides, 4
      mutants (I38 V, I38A, I38F and Q84A) were obtained by site-directed mutagenesis
      based on molecular modeling and sequence alignment. The kinetic analysis
      indicated that mutants I38 V and I38A exhibited a 1.7- and 1.4-fold increase over
      the wild type enzyme in catalytic efficiency (k(cat)/K(m)) against pNP-alpha-Gal,
      respectively, while mutant I38F showed a 3.5-fold decrease against pNP-alpha-Gal
      and mutant Q84A almost completely lost its activity. All the results suggest that
      I38 and Q84 sites play a vital role in enzyme activity probably due to their
      steric and polar effects on the predicted "tunnel" structure and NAD+ binding to
      the enzyme.

PMID- 24564903
TI  - Identification of substrate-binding and selectivity-related residues of
      maltooligosyltrehalose synthase from the thermophilic archaeon Sulfolobus
      solfataricus ATCC 35092.
AB  - Maltooligosyltrehalose synthase (MTSase) is a key enzyme in the synthesis of
      trehalose. Computer simulations using AutoDock and NAMD were employed to assess
      the substrate-binding and selectivity-related residues of MTSase. We introduced
      mutations at residues D411, D610, and R614 to determine the substrate-binding
      residues of Sulfolobus solfataricus ATCC 35092 MTSase, and introduced mutations
      at residues P402, A406, and V426 to investigate the enzyme's selectivity-related
      residues. Kinetic studies of D411A, D610A, and R614A MTSases reveal significant
      reductions in catalytic efficiency and cause increase in the transition-state
      energy of mutant MTSases, indicating that residues D411, D610, and R614 form
      hydrogen bonds to the substrate. Compared with wild-type MTSase, the hydrolysis:
      transglycosylation selectivity ratio was significantly decreased for P402Q and
      significantly increased for A406S MTSases, while the ratio for V426T MTSase
      showed little change. The results suggest that P402 and A406 residues are
      selectivity-related. 

PMID- 24564904
TI  - Critical residues of class II PHA synthase for expanding the substrate
      specificity and enhancing the biosynthesis of polyhydroxyalkanoate.
AB  - This study describes protein model of type II Pseudomonas putida GPo1 synthase
      (PhaC1(Pp)) and using single or multiple points mutagenesis to identify the
      beneficial amino acid residues that change the PHA accumulation and the substrate
      chain-length specificity of type II PHA synthase. The P. putida GPp104 PHA- was
      used as a host for evaluating the substrate specificity and PHA yield of the
      mutated PhaC1(Pp). The evolved PhaC1(Pp) were coexpressed with beta-ketothiolase
      (phbA(Re)) and the acetoacetyl-CoA reductase (phbB(Re)) to supply sufficient
      short-chain length (R)-3-hydroxyacyl-CoA as a substrate. A single point mutation
      at L484V remarkably enhanced the monomer ratio of (R)-3-hydroxybutyrate in a PHA
      accumulation experiment. Saturation mutagenesis experiment at 484 concluded that
      Val is the most favorable amino acid in PhaC1(Pp) for incorporating (R)-3
      hydroxybutyrate unit synthesis. In addition, a single mutation at Q481M, S482G
      and A547V obviously increased PHA yields. Q481M and S482G enhanced the (R)-3
      hydroxyhexanoate monomer composition in the PHA accumulation by P. putida GPp104
      PHA-. This is the first data that spotlighted the important effect of Leu484 on
      substrate specificity of PHA synthase and Ala547 on the PHA accumulation.

PMID- 24564905
TI  - An approach for dynamical network reconstruction of simple network motifs.
AB  - BACKGROUND: One of the most important projects in the post-genome-era is the
      systemic identification of biological network. The almost of studies for network
      identification focused on the improvement of computational efficiency in large
      scale network inference of complex system with cyclic relations and few attempted
      have been done for answering practical problem occurred in real biological
      systems. In this study, we focused to evaluate inferring performance of our
      previously proposed method for inferring biological network on simple network
      motifs. RESULTS: We evaluated the network inferring accuracy and efficiency of
      our previously proposed network inferring algorithm, by using 6 kinds of repeated
      appearance of highly significant network motifs in the regulatory network of E.
      coli proposed by Shen-Orr et al and Herrgard et al, and 2 kinds of network motif
      in S. cerevisiae proposed by Lee et. al. As a result, our method could
      reconstruct about 40% of interactions in network motif from time-series data set.
      Moreover the introduction of time-series data of one-factor disrupted model could
      remarkably improved the performance of network inference. CONCLUSIONS: The
      results of network inference examination of E. coli network motif shows that our
      network inferring algorithm was able to apply to typical topology of biological
      network. A continuous examination of inferring well established network motif in
      biology would strengthen the applicability of our algorithm to the realistic
      biological network.

PMID- 24564906
TI  - Surveillance for antimicrobial drug resistance in under-resourced countries.
AB  - Antimicrobial drug resistance is usually not monitored in under-resourced
      countries because they lack surveillance networks, laboratory capacity, and
      appropriate diagnostics. This accelerating problem accounts for substantial
      number of excess deaths, especially among infants. Infections particularly
      affected by antimicrobial drug resistance include tuberculosis, malaria, severe
      acute respiratory infections, and sepsis caused by gram-negative bacteria.
      Nonetheless, mapping antimicrobial drug resistance is feasible in under-resourced
      countries, and lessons can be learned from previous successful efforts. Specimen
      shipping conditions, data standardization, absence of contamination, and adequate
      diagnostics must be ensured. As a first step toward solving this problem, we
      propose that a road map be created at the international level to strengthen
      antimicrobial resistance surveillance in under-resourced countries. This effort
      should include a research agenda; a map of existing networks and recommendations
      to unite them; and a communication plan for national, regional, and international
      organizations and funding agencies. 

PMID- 24564907
TI  - Are MEFV mutations susceptibility factors in enthesitis-related arthritis
      patients in the eastern Mediterranean?
AB  - OBJECTIVES: Enthesitis-related arthritis (ERA), is a complex genetic disease.
      Although HLA-B27 is well established, it does not explain all the genetic load in
      ERA. Familial Mediterranean fever (FMF), caused by mutations in the MEFV gene, is
      a frequent autoinflammatory disorder in the eastern Mediterranean. METHODS: We
      investigated the clinical and imaging features of 53 ERA patients, as well as the
      frequency of MEFV gene mutations in those who were HLA-B27 negative. RESULTS: The
      mean age of the patients was 13.3+/-2.2 years and 49 were boys. Peripheral
      arthritis was present in all and sacroiletis in 26 patients. Ultrasonography
      showed enthesitis in 6 patients of the tendons, whereas these were assessed to be
      normal by physical examination. Forty patients (75.5%) were positive for HLA-B27.
      MEFV analysis was performed for patients who were HLA-B27 negative. One patient
      refused MEFV analysis. 9 patients carried MEFV mutations: 2 patients were
      homozygous for M694V (both patients were subsequently started colchicine along
      with ERA treatment), 5 patients were heterozygous for M694V mutation, 1 patient
      was heterozygous for E148Q, and 1 patient was heterozygous for K695R mutation.
      None of the patients had features suggesting FMF at diagnosis of ERA; 1 patient
      subsequently developed typical FMF attacks. CONCLUSIONS: Our findings suggest
      that MEFV mutations may represent a susceptibility factor for ERA in the
      populations of the eastern Mediterranean.

PMID- 24564908
TI  - The important role of lipids in the epidermis and their role in the formation and
      maintenance of the cutaneous barrier.

PMID- 24564910
TI  - Synthesis of extended graphdiyne wires by vicinal surface templating.
AB  - Surface-assisted covalent synthesis currently evolves into an important approach
      for the fabrication of functional nanostructures at interfaces. Here, we employ
      scanning tunneling microscopy to investigate the homocoupling reaction of linear,
      terminal alkyne-functionalized polyphenylene building-blocks on noble metal
      surfaces under ultrahigh vacuum. On the flat Ag(111) surface, thermal activation
      triggers a variety of side-reactions resulting in irregularly branched polymeric
      networks. Upon alignment along the step-edges of the Ag(877) vicinal surface
      drastically improves the chemoselectivity of the linking process permitting the
      controlled synthesis of extended-graphdiyne wires with lengths reaching 30 nm.
      The ideal hydrocarbon scaffold is characterized by density functional theory as a
      1D, direct band gap semiconductor material with both HOMO and LUMO-derived bands
      promisingly isolated within the electronic structure. The templating approach
      should be applicable to related organic precursors and different reaction schemes
      thus bears general promise for the engineering of novel low-dimensional carbon
      based materials. 

PMID- 24564909
TI  - Dynamic protein interaction modules in human hepatocellular carcinoma
      progression.
AB  - BACKGROUND: Gene expression profiles have been frequently integrated with the
      human protein interactome to uncover functional modules under specific conditions
      like disease state. Beyond traditional differential expression analysis,
      differential co-expression analysis has emerged as a robust approach to reveal
      condition-specific network modules, with successful applications in a few human
      disease studies. Hepatocellular carcinoma (HCC), which is often interrelated with
      the Hepatitis C virus, typically develops through multiple stages. A
      comprehensive investigation of HCC progression-specific differential co
      expression modules may advance our understanding of HCC's pathophysiological
      mechanisms. RESULTS: Compared with differentially expressed genes, differentially
      co-expressed genes were found more likely enriched with Hepatitis C virus binding
      proteins and cancer-mutated genes, and they were clustered more densely in the
      human reference protein interaction network. These observations indicated that a
      differential co-expression approach could outperform the standard differential
      expression network analysis in searching for disease-related modules. We then
      proposed a differential co-expression network approach to uncover network modules
      involved in HCC development. Specifically, we discovered subnetworks that
      enriched differentially co-expressed gene pairs in each HCC transition stage, and
      further resolved modules with coherent co-expression change patterns over all HCC
      developmental stages. Our identified network modules were enriched with HCC
      related genes and implicated in cancer-related biological functions. In
      particular, APC and YWHAZ were highlighted as two most remarkable genes in the
      network modules, and their dynamic interaction partnership was resolved in HCC
      development. CONCLUSIONS: We demonstrated that integration of differential co
      expression with the protein interactome could outperform the traditional
      differential expression approach in discovering network modules of human
      diseases. In our application of this approach to HCC's gene expression data, we
      successfully identified subnetworks with marked differential co-expression in
      individual HCC stage transitions and network modules with coherent co-expression
      change patterns over all HCC developmental stages. Our results shed light on
      subtle HCC mechanisms, including temporal activation and dismissal of pivotal
      functions and dynamic interaction partnerships of key genes.

PMID- 24564911
TI  - Association of academic performance of premedical students to satisfaction and
      engagement in a short training program: a cross sectional study presenting gender
      differences.
AB  - BACKGROUND: It is important that students have a high academic engagement and
      satisfaction in order to have good academic achievement. No study measures
      association of these elements in a short training program. This study aimed to
      measure the correlation between academic achievement, satisfaction and engagement
      dimensions in a short training program among premedical students. METHODS: We
      carried out a cross sectional study, in August 2013, at Cercle d'Etudiants,
      Ingenieurs, Medecins et Professeurs de Lycee pour le Triomphe de l'Excellence
      (CEMPLEX) training center, a center which prepares students for the national
      common entrance examination into medical schools in Cameroon. We included all
      students attending this training center during last examination period. They were
      asked to fill out a questionnaire on paper. Academic engagement was measured
      using three dimensions: vigor, dedication and absorption. Satisfaction to
      lessons, for each learning subject was collected. Academic achievement was
      calculated using mean of the score of all learning subjects affected with their
      coefficient. Pearson coefficient (r) and multiple regression models were used to
      measure association. A p value < 0.05 was statistically significant. RESULTS: In
      total, 180 students were analyzed. In univariate linear analysis, we found
      correlation with academic achievement for vigor (r = 0.338, p = 0.006) and
      dedication (r = 0.287, p = 0.021) only in male students. In multiple regression
      linear analysis, academic engagement and satisfaction were correlated to academic
      achievement only in male students (R2 = 0.159, p = 0.035). No correlation was
      found in female students and in all students. The independent variables (vigor,
      dedication, absorption and satisfaction) explained 6.8-24.3% of the variance of
      academic achievement. CONCLUSION: It is only in male students that academic
      engagement and satisfaction to lessons are correlated to academic achievement in
      this short training program for premedical students and this correlation is weak.

PMID- 24564912
TI  - First case of a naturally acquired human infection with Plasmodium cynomolgi.
AB  - Since 1960, a total of seven species of monkey malaria have been reported as
      transmissible to man by mosquito bite: Plasmodium cynomolgi, Plasmodium
      brasilianum, Plasmodium eylesi, Plasmodium knowlesi, Plasmodium inui, Plasmodium
      schwetzi and Plasmodium simium. With the exception of P. knowlesi, none of the
      other species has been found to infect humans in nature. In this report, it is
      described the first known case of a naturally acquired P. cynomolgi malaria in
      humans.The patient was a 39-year-old woman from a malaria-free area with no
      previous history of malaria or travel to endemic areas. Initially, malaria was
      diagnosed and identified as Plasmodium malariae/P. knowlesi by microscopy in the
      Terengganu State Health Department. Thick and thin blood films stained with 10%
      Giemsa were performed for microscopy examination. Molecular species
      identification was performed at the Institute for Medical Research (IMR,
      Malaysia) and in the Malaria & Emerging Parasitic Diseases Laboratory (MAPELAB,
      Spain) using different nested PCR methods.Microscopic re-examination in the IMR
      showed characteristics of Plasmodium vivax and was confirmed by a nested PCR
      assay developed by Snounou et al. Instead, a different PCR assay plus sequencing
      performed at the MAPELAB confirmed that the patient was infected with P.
      cynomolgi and not with P. vivax.This is the first report of human P. cynomolgi
      infection acquired in a natural way, but there might be more undiagnosed or
      misdiagnosed cases, since P. cynomolgi is morphologically indistinguishable from
      P. vivax, and one of the most used PCR methods for malaria infection detection
      may identify a P. cynomolgi infection as P. vivax.Simian Plasmodium species may
      routinely infect humans in Southeast Asia. New diagnostic methods are necessary
      to distinguish between the human and monkey malaria species. Further
      epidemiological studies, incriminating also the mosquito vector(s), must be
      performed to know the relevance of cynomolgi malaria and its implication on human
      public health and in the control of human malaria.The zoonotic malaria cannot be
      ignored in view of increasing interactions between man and wild animals in the
      process of urbanization. 

PMID- 24564913
TI  - Divergent dysregulation of gene expression in murine models of fragile X syndrome
      and tuberous sclerosis.
AB  - BACKGROUND: Fragile X syndrome and tuberous sclerosis are genetic syndromes that
      both have a high rate of comorbidity with autism spectrum disorder (ASD). Several
      lines of evidence suggest that these two monogenic disorders may converge at a
      molecular level through the dysfunction of activity-dependent synaptic
      plasticity. METHODS: To explore the characteristics of transcriptomic changes in
      these monogenic disorders, we profiled genome-wide gene expression levels in
      cerebellum and blood from murine models of fragile X syndrome and tuberous
      sclerosis. RESULTS: Differentially expressed genes and enriched pathways were
      distinct for the two murine models examined, with the exception of immune
      response-related pathways. In the cerebellum of the Fmr1 knockout (Fmr1-KO)
      model, the neuroactive ligand receptor interaction pathway and gene sets
      associated with synaptic plasticity such as long-term potentiation, gap junction,
      and axon guidance were the most significantly perturbed pathways. The
      phosphatidylinositol signaling pathway was significantly dysregulated in both
      cerebellum and blood of Fmr1-KO mice. In Tsc2 heterozygous (+/-) mice, immune
      system-related pathways, genes encoding ribosomal proteins, and glycolipid
      metabolism pathways were significantly changed in both tissues. CONCLUSIONS: Our
      data suggest that distinct molecular pathways may be involved in ASD with known
      but different genetic causes and that blood gene expression profiles of Fmr1-KO
      and Tsc2+/- mice mirror some, but not all, of the perturbed molecular pathways in
      the brain.

PMID- 24564915
TI  - A combined approach for genome wide protein function annotation/prediction.
AB  - BACKGROUND: Today large scale genome sequencing technologies are uncovering an
      increasing amount of new genes and proteins, which remain uncharacterized.
      Experimental procedures for protein function prediction are low throughput by
      nature and thus can't be used to keep up with the rate at which new proteins are
      discovered. On the other hand, proteins are the prominent stakeholders in almost
      all biological processes, and therefore the need to precisely know their
      functions for a better understanding of the underlying biological mechanism is
      inevitable. The challenge of annotating uncharacterized proteins in functional
      genomics and biology in general motivates the use of computational techniques
      well orchestrated to accurately predict their functions. METHODS: We propose a
      computational flow for the functional annotation of a protein able to assign the
      most probable functions to a protein by aggregating heterogeneous information.
      Considered information include: protein motifs, protein sequence similarity, and
      protein homology data gathered from interacting proteins, combined with data from
      highly similar non-interacting proteins (hereinafter called Similactors).
      Moreover, to increase the predictive power of our model we also compute and
      integrate term specific relationships among functional terms based on Gene
      Ontology (GO). RESULTS: We tested our method on Saccharomyces Cerevisiae and Homo
      sapiens species proteins. The aggregation of different structural and functional
      evidence with GO relationships outperforms, in terms of precision and accuracy of
      prediction than the other methods reported in literature. The predicted precision
      and accuracy is 100% for more than half of the input set for both species;
      overall, we obtained 85.38% precision and 81.95% accuracy for Homo sapiens and
      79.73% precision and 80.06% accuracy for Saccharomyces Cerevisiae species
      proteins.

PMID- 24564914
TI  - The effect of ovarian puncture on the endocrine profile of PCOS patients who
      undergo IVM.
AB  - BACKGROUND: To examine whether ovarian puncture for immature oocyte retrieval and
      in-vitro maturation (IVM) has an effect on the endocrine profile of patients with
      polycystic ovary syndrome (PCOS). METHODS: Twenty-two consecutive patients with
      PCOS undergoing IVM treatment were included. Serum anti-Mullerian hormone (AMH),
      sex hormone-binding globulin (SHBG), total testosterone (TT) and luteinized
      hormone (LH) levels were analyzed at the start of the cycle, on the day of
      immature oocyte retrieval (OR) and at fixed intervals thereafter, for up to three
      months after OR. RESULTS: Five days after OR circulating AMH, TT, calculated free
      testosterone (FTc), and LH levels were significantly reduced and circulating SHBG
      was significantly increased. Two weeks after OR, TT, FTc and LH remained reduced,
      whereas circulating AMH and SHBG levels recovered to pre-puncture values. Three
      months after OR, all circulating hormone levels had recovered to baseline values.
      CONCLUSION: Ovarian puncture for the retrieval of immature oocytes and IVM in
      patients with PCOS has a significant impact on the ovarian endocrine profile, but
      this impact is brief and transient.

PMID- 24564916
TI  - A new approach to enhance the performance of decision tree for classifying gene
      expression data.
AB  - BACKGROUND: Gene expression data classification is a challenging task due to the
      large dimensionality and very small number of samples. Decision tree is one of
      the popular machine learning approaches to address such classification problems.
      However, the existing decision tree algorithms use a single gene feature at each
      node to split the data into its child nodes and hence might suffer from poor
      performance specially when classifying gene expression dataset. RESULTS: By using
      a new decision tree algorithm where, each node of the tree consists of more than
      one gene, we enhance the classification performance of traditional decision tree
      classifiers. Our method selects suitable genes that are combined using a linear
      function to form a derived composite feature. To determine the structure of the
      tree we use the area under the Receiver Operating Characteristics curve (AUC).
      Experimental analysis demonstrates higher classification accuracy using the new
      decision tree compared to the other existing decision trees in literature.
      CONCLUSION: We experimentally compare the effect of our scheme against other well
      known decision tree techniques. Experiments show that our algorithm can
      substantially boost the classification performance of the decision tree.

PMID- 24564917
TI  - Leadership and organizational ethics: the three dimensional African perspectives.
AB  - This paper addresses the past, present and future aspects of African leadership
      and organizational ethics that have, are and will be key for any organization to
      sustain its systems and structures. Organizational ethics revolves around written
      and/or unwritten guidelines, ethical values, principles, rules and standards,
      that are drawn from the harmonious coexistence with the biosphere and it is how
      these elements are applied that dictates the style of leadership and the ethical
      thinking of the leaders. Africa has a wide range of complexities which are
      compounded by, inter alia, tribal divisiveness, selfish leadership, wealth
      inequality, and massive unemployment. Africans tend to draw their leadership and
      ethical practices and reflections from the events in the environment with which
      they have interacted for many years. However, in order to fully address and
      understand the African perspective in leadership and organizational ethics, a
      broad comprehension of the African diverse and complex landscape is needed
      through unravelling of the three dimensional existence of the people. African
      ethics, developed over time, unifies organizations and leadership since it is
      part of life and is practised, sub-consciously or unconsciously, by the people as
      they transform from one practice to the other, and during intergenerational
      transitions. Globalization, liberalization, technological changes and
      advancement, and market changes are rapidly transforming the environment in which
      organizations operate. In such a situation, an effective and true leader cannot
      be rigid but should be flexible, with the ability to use different leadership
      styles whenever the situation calls for it. Only those leaders with a three
      dimensional perspective live inspiring lives, live with a cause and adopt
      organizational ethics and leadership styles that will stand the test of time.
      Despite Africa being the cradle of humankind, leadership and organizational
      ethics is still in its infancy and wanting, even with the new generation of young
      leaders. The future outlook of African organizational ethics and leadership is to
      be found in the intersection of changes in technology, life style, demographics
      and geopolitics with new trends emerging in global polity and economy. 

PMID- 24564918
TI  - Four-body atomic potential for modeling protein-ligand binding affinity:
      application to enzyme-inhibitor binding energy prediction.
AB  - BACKGROUND: Models that are capable of reliably predicting binding affinities for
      protein-ligand complexes play an important role the field of structure-guided
      drug design. METHODS: Here, we begin by applying the computational geometry
      technique of Delaunay tessellation to each set of atomic coordinates for over
      1400 diverse macromolecular structures, for the purpose of deriving a four-body
      statistical potential that serves as a topological scoring function. Next, we
      identify a second, independent set of three hundred protein-ligand complexes,
      having both high-resolution structures and known dissociation constants. Two
      thirds of these complexes are randomly selected to train a predictive model of
      binding affinity as follows: two tessellations are generated in each case, one
      for the entire complex and another strictly for the isolated protein without its
      bound ligand, and a topological score is computed for each tessellation with the
      four-body potential. Predicted protein-ligand binding affinity is then based on
      an empirically derived linear function of the difference between both topological
      scores, one that appropriately scales the value of this difference. RESULTS: A
      comparison between experimental and calculated binding affinity values over the
      two hundred complexes reveals a Pearson's correlation coefficient of r = 0.79
      with a standard error of SE = 1.98 kcal/mol. To validate the method, we similarly
      generated two tessellations for each of the remaining protein-ligand complexes,
      computed their topological scores and the difference between the two scores for
      each complex, and applied the previously derived linear transformation of this
      topological score difference to predict binding affinities. For these one hundred
      complexes, we again observe a correlation of r = 0.79 (SE = 1.93 kcal/mol)
      between known and calculated binding affinities. Applying our model to an
      independent test set of high-resolution structures for three hundred diverse
      enzyme-inhibitor complexes, each with an experimentally known inhibition
      constant, also yields a correlation of r = 0.79 (SE = 2.39 kcal/mol) between
      experimental and calculated binding energies. CONCLUSIONS: Lastly, we generate
      predictions with our model on a diverse test set of one hundred protein-ligand
      complexes previously used to benchmark 15 related methods, and our correlation of
      r = 0.66 between the calculated and experimental binding energies for this
      dataset exceeds those of the other approaches. Compared with these related
      prediction methods, our approach stands out based on salient features that
      include the reliability of our model, combined with the rapidity of the generated
      predictions, which are less than one second for an average sized complex.

PMID- 24564919
TI  - A 3D multiscale model of cancer stem cell in tumor development.
AB  - BACKGROUND: Recent reports indicate that a subgroup of tumor cells named cancer
      stem cells (CSCs) or tumor initiating cells (TICs) are responsible for tumor
      initiation, growth and drug resistance. This subgroup of tumor cells has self
      renewal capacity and could differentiate into heterogeneous tumor cell
      populations through asymmetric proliferation. The idea of CSC provides
      informative insights into tumor initiation, metastasis and treatment. However,
      the underlying mechanisms of CSCs regulating tumor behaviors are unclear due to
      the complex cancer system. To study the functions of CSCs in the complex tumor
      system, a few mathematical modeling studies have been proposed. Whereas, the
      effect of microenvironment (mE) factors, the behaviors of CSCs, progenitor tumor
      cells (PCs) and differentiated tumor cells (TCs), and the impact of CSC fraction
      and signaling heterogeneity, are not adequately explored yet. METHODS: In this
      study, a novel 3D multi-scale mathematical modeling is proposed to investigate
      the behaviors of CSCsin tumor progressions. The model integrates CSCs, PCs, and
      TCs together with a few essential mE factors. With this model, we simulated and
      investigated the tumor development and drug response under different CSC content
      and heterogeneity. RESULTS: The simulation results shown that the fraction of
      CSCs plays a critical role in driving the tumor progression and drug resistance.
      It is also showed that the pure chemo-drug treatment was not a successful
      treatment, as it resulted in a significant increase of the CSC fraction. It
      further shown that the self-renew heterogeneity of the initial CSC population is
      a cause of the heterogeneity of the derived tumors in terms of the CSC fraction
      and response to drug treatments. CONCLUSIONS: The proposed 3D multi-scale model
      provides a new tool for investigating the behaviors of CSC in CSC-initiated
      tumors, which enables scientists to investigate and generate testable hypotheses
      about CSCs in tumor development and drug response under different
      microenvironments and drug perturbations.

PMID- 24564921
TI  - Attrition of full-time faculty from schools of nursing with baccalaureate and
      graduate programs, 2010 to 2011.
AB  - The shortage of qualified faculty has been consistently reported as a major
      barrier impeding acceptance of all qualified applicants into nursing programs. In
      addition to faculty recruitment, the attrition of faculty is also a concern for
      schools of nursing. In this study, we found that nationally 11.8% of full-time
      faculty who worked in 2010 left their full-time jobs by 2011. Nearly half of
      total attrition, or 5.7% of full-time faculty members, were related to leaving
      for nonacademic nursing positions, whereas another 20% of attrition, or 2.4% of
      full-time faculty, resulted from retirement. Nearly 20% of faculty egressions, or
      2.2% of full-time faculty, was due to leaving for nursing administrative
      positions or full-time faculty positions in an academic setting. Leaving for part
      time faculty positions made up slightly more than 10% of faculty attrition or
      1.3% of full-time faculty. Our bivariate analysis identifies distinctive academic
      and demographic profiles of faculty who left full-time positions for different
      reasons, and our multivariate analysis further shows that different individual
      and institutional attributes are significantly associated with different types of
      attrition. 

PMID- 24564920
TI  - Building a microphysiological skin model from induced pluripotent stem cells.
AB  - The discovery of induced pluripotent stem cells (iPSCs) in 2006 was a major
      breakthrough for regenerative medicine. The establishment of patient-specific
      iPSCs has created the opportunity to model diseases in culture systems, with the
      potential to rapidly advance the drug discovery field. Current methods of drug
      discovery are inefficient, with a high proportion of drug candidates failing
      during clinical trials due to low efficacy and/or high toxicity. Many drugs fail
      toxicity testing during clinical trials, since the cells on which they have been
      tested do not adequately model three-dimensional tissues or their interaction
      with other organs in the body. There is a need to develop microphysiological
      systems that reliably represent both an intact tissue and also the interaction of
      a particular tissue with other systems throughout the body. As the port of entry
      for many drugs is via topical delivery, the skin is the first line of exposure,
      and also one of the first organs to demonstrate a reaction after systemic drug
      delivery. In this review, we discuss our strategy to develop a microphysiological
      system using iPSCs that recapitulates human skin for analyzing the interactions
      of drugs with the skin. 

PMID- 24564923
TI  - A networks method for ranking microRNA dysregulation in cancer.
AB  - BACKGROUND: Despite the lack of agreement on their exact roles, it is known that
      miRNAs contribute to cancer progression. Many studies utilize methods to detect
      differential regulation of miRNA expression. It is prohibitively expensive to
      examine all potentially dysregulated miRNAs and traditionally, researchers have
      focused their efforts on the most extremely dysregulated miRNAs. These methods
      may overlook the contribution of less differentially expressed but more
      functionally relevant miRNAs. The purpose of this study was to outline a method
      that not only utilizes differential expression but ranks miRNAs based on the
      functional relevance of their targets. This work uses a networks based approach
      to determine the sum node degree for all experimentally verified miRNA targets to
      identify potential regulators of prostate cancer initiation, progression and
      metastasis. RESULTS: Here, we present a method for identifying functionally
      relevant miRNAs that contribute to prostate cancer development. This paper shows
      that miRNAs preferentially regulate highly connected, central proteins within a
      protein-protein interaction network. Known targets of miRNAs differentially
      regulated during prostate cancer progression are enriched in pathways with known
      involvement in tumorigenesis. To demonstrate the applicability of our method, we
      utilized a unique model of prostate cancer progression to identify five miRNAs
      that may contribute to the oncogenic state of the cell. Three of these miRNAs
      have been shown by other studies to have a role in cancer but their exact role in
      prostate cancer remains undefined. CONCLUSION: Developing methods to determine
      which miRNAs to carry forward into biological and biochemical analyses is
      important as traditional approaches often overlook miRNAs that contribute to
      oncogenesis. Our method applied to a model of prostate cancer progression was
      able to identify miRNAs with roles in prostate cancer development.

PMID- 24564922
TI  - Evaluation of respiratory syncytial virus group A and B genotypes among
      nosocomial and community-acquired pediatric infections in Southern Brazil.
AB  - BACKGROUND: Respiratory syncytial virus (RSV) is the main cause of lower
      respiratory tract illness in children worldwide. Molecular analyses show two
      distinct RSV groups (A and B) that comprise different genotypes. This variability
      contributes to the capacity of RSV to cause yearly outbreaks. These RSV genotypes
      circulate within the community and within hospital wards. RSV is currently the
      leading cause of nosocomial respiratory tract infections in pediatric
      populations. The aim of this study was to evaluate the G protein gene diversity
      of RSV amplicons. METHODS: Nasopharyngeal aspirate samples were collected from
      children with nosocomial or community-acquired infections. Sixty-three RSV
      samples (21 nosocomial and 42 community-acquired) were evaluated and classified
      as RSV-A or RSV-B by real-time PCR. Sequencing of the second variable region of
      the G protein gene was performed to establish RSV phylogenetics. RESULTS: We
      observed co-circulation of RSV-A and RSV-B, with RSV-A as the predominant group.
      All nosocomial and community-acquired RSV-A samples were from the same
      phylogenetic group, comprising the NA1 genotype, and all RSV-B samples
      (nosocomial and community-acquired) were of the BA4 genotype. Therefore, in both
      RSV groups (nosocomial and community-acquired), the isolates belonged to only one
      genotype in circulation. CONCLUSIONS: This is the first study to describe
      circulation of the NA1 RSV genotype in Brazil. Furthermore, this study showed
      that the BA4 genotype remains in circulation. Deciphering worldwide RSV genetic
      variability will aid vaccine design and development.

PMID- 24564925
TI  - SMS messages increase adherence to rapid diagnostic test results among malaria
      patients: results from a pilot study in Nigeria.
AB  - BACKGROUND: The World Health Organization now recommends parasitological
      confirmation for malaria case management. Rapid diagnostic tests (RDTs) for
      malaria are an accurate and simple diagnostic to confirm parasite presence in
      blood. However, where they have been deployed, adherence to RDT results has been
      poor, especially when the test result is negative. Few studies have examined
      adherence to RDTs distributed or purchased through the private sector. METHODS:
      The Rapid Examination of Malaria and Evaluation of Diagnostic Information
      (REMEDI) study assessed the acceptability of and adherence to RDT results for
      patients seeking care from private sector drug retailers in two cities in Oyo
      State in south-west Nigeria. In total, 465 adult participants were enrolled upon
      exit from a participating drug shop having purchased anti-malaria drugs for
      themselves. Participants were given a free RDT and the appropriate treatment
      advice based on their RDT result. Short Message Service (SMS) text messages
      reiterating the treatment advice were sent to a randomly selected half of the
      participants one day after being tested. Participants were contacted via phone
      four days after the RDT was conducted to assess adherence to the RDT information
      and treatment advice. RESULTS: Adherence to RDT results was 14.3 percentage
      points (P-val <0.001) higher in the treatment group who were sent the SMS. The
      higher adherence in the treatment group was robust to several specification tests
      and the estimated difference in adherence ranged from 9.7 to 16.1 percentage
      points. Further, the higher adherence to the treatment advice was specific to the
      treatment advice for anti-malarial drugs and not other drugs purchased to treat
      malaria symptoms in the RDT-negative participants who bought both anti-malarial
      and symptom drugs. There was no difference in adherence for the RDT-positive
      participants who were sent the SMS. CONCLUSIONS: SMS text messages substantially
      increased adherence to RDT results for patients seeking care for malaria from
      privately owned drug retailers in Nigeria and may be a simple and cost-effective
      means for boosting adherence to RDT results if and when RDTs are introduced as a
      commercial retail product.

PMID- 24564924
TI  - Prediction of protein interaction types based on sequence and network features.
AB  - BACKGROUND: Protein interactions mediate a wide spectrum of functions in various
      cellular contexts. Functional versatility of protein complexes is due to a broad
      range of structural adaptations that determine their binding affinity, the number
      of interaction sites, and the lifetime. In terms of stability it has become
      customary to distinguish between obligate and non-obligate interactions dependent
      on whether or not the protomers can exist independently. In terms of spatio
      temporal control protein interactions can be either simultaneously possible (SP)
      or mutually exclusive (ME). In the former case a network hub interacts with
      several proteins at the same time, offering each of them a separate interface,
      while in the latter case the hub interacts with its partners one at a time via
      the same binding site. So far different types of interactions were distinguished
      based on the properties of the corresponding binding interfaces derived from
      known three-dimensional structures of protein complexes. RESULTS: Here we present
      PiType, an accurate 3D structure-independent computational method for classifying
      protein interactions into simultaneously possible (SP) and mutually exclusive
      (ME) as well as into obligate and non-obligate. Our classifier exploits features
      of the binding partners predicted from amino acid sequence, their functional
      similarity, and network topology. We find that the constituents of non-obligate
      complexes possess a higher degree of structural disorder, more short linear
      motifs, and lower functional similarity compared to obligate interaction partners
      while SP and ME interactions are characterized by significant differences in
      network topology. Each interaction type is associated with a distinct set of
      biological functions. Moreover, interactions within multi-protein complexes tend
      to be enriched in one type of interactions. CONCLUSION: PiType does not rely on
      atomic structures and is thus suitable for characterizing proteome-wide
      interaction datasets. It can also be used to identify sub-modules within protein
      complexes. PiType is available for download as a self-installing package from
      http://webclu.bio.wzw.tum.de/PiType/PiType.zip.

PMID- 24564926
TI  - Better primer design for metagenomics applications by increasing taxonomic
      distinguishability.
AB  - Current methods of understanding microbiome composition and structure rely on
      accurately estimating the number of distinct species and their relative
      abundance. Most of these methods require an efficient PCR whose forward and
      reverse primers bind well to the same, large number of identifiable species, and
      produce amplicons that are unique. It is therefore not surprising that currently
      used universal primers designed many years ago are not as efficient and fail to
      bind to recently cataloged species. We propose an automated general method of
      designing PCR primer pairs that abide by primer design rules and uses current
      sequence database as input. Since the method is automated, primers can be
      designed for targeted microbial species or updated as species are added or
      deleted from the database. In silico experiments and laboratory experiments
      confirm the efficacy of the newly designed primers for metagenomics applications.

PMID- 24564927
TI  - Hemoperitoneum in advanced abdominal pregnancy with a live baby: a case report.
AB  - BACKGROUND: Abdominal pregnancy is a rare condition which is usually missed
      during prenatal assessment particularly in settings lacking routine ultrasound
      surveillance. We report a case of abdominal pregnancy at 32 weeks, which is most
      likely to have been a tubal abortion with secondary implantation, leading to
      delivery of a healthy baby girl weighing 1.7 kg. CASE PRESENTATION: A 22-year-old
      woman, gravid 3 para 2 was referred to our centre from a district hospital with
      complaint of generalized abdominal pain and reduced fetal movements. Although the
      initial abdomino-pelvic ultrasound done at our centre was read as normal, there
      was subsequently a strong clinical suspicion of abdominal pregnancy, which was
      confirmed by a second ultrasound. The patient underwent laparotomy and was found
      to have an intact uterus with a viable fetus floating in the abdominal cavity
      without its amniotic sac and with hemoperitoneum of 1litre. The baby was
      extracted successfully; the placenta was found to be deeply implanted on the
      right cornual side extending to the fundus superiorly. Wedge resection of the
      cornual area and fundus was performed to remove the placenta. Intraoperatively,
      one unit of blood was transfused due to severe anemia prior to surgery. Both the
      mother and the baby were discharged home in good condition. CONCLUSION: Abdominal
      pregnancy can be missed prenatally even when an imaging (ultrasound) facility is
      available. Emphasis should be placed on clinical assessment and thorough
      evaluation of patients.

PMID- 24564928
TI  - Drought and epidemic typhus, central Mexico, 1655-1918.
AB  - Epidemic typhus is an infectious disease caused by the bacterium Rickettsia
      prowazekii and transmitted by body lice (Pediculus humanus corporis). This
      disease occurs where conditions are crowded and unsanitary. This disease
      accompanied war, famine, and poverty for centuries. Historical and proxy climate
      data indicate that drought was a major factor in the development of typhus
      epidemics in Mexico during 1655-1918. Evidence was found for 22 large typhus
      epidemics in central Mexico, and tree-ring chronologies were used to reconstruct
      moisture levels over central Mexico for the past 500 years. Below-average tree
      growth, reconstructed drought, and low crop yields occurred during 19 of these 22
      typhus epidemics. Historical documents describe how drought created large numbers
      of environmental refugees that fled the famine-stricken countryside for food
      relief in towns. These refugees often ended up in improvised shelters in which
      crowding encouraged conditions necessary for spread of typhus. 

PMID- 24564929
TI  - Discovery of metabolite biomarkers: flux analysis and reaction-reaction network
      approach.
AB  - BACKGROUND: Metabolism is a vital cellular process, and its malfunction can be a
      major contributor to many human diseases. Metabolites can serve as a metabolic
      disease biomarker. An detection of such biomarkers plays a significant role in
      the study of biochemical reaction and signaling networks. Early research mainly
      focused on the analysis of the metabolic networks. The issue of integrating
      metabolite networks with other available biological data to reveal the mechanics
      of disease-metabolite associations is an important and interesting challenge.
      RESULTS: In this article, we propose two new approaches for the identification of
      metabolic biomarkers with the incorporation of disease specific gene expression
      data and the genome-scale human metabolic network. The first approach is to
      compare the flux interval between the normal and disease sample so as to identify
      reaction biomarkers. The second one is based on the Reaction-Reaction Network
      (RRN) to reveal the significant reactions. These two approaches utilize reaction
      flux obtained by a Linear Programming (LP) based method that can contribute to
      the discovery of potential novel biomarkers. CONCLUSIONS: Biomarker
      identification is an important issue in studying biochemical reactions and
      signaling networks. Two efficient and effective computational methods are
      proposed for the identification of biomarkers in this article. Furthermore, the
      biomarkers found by our proposed methods are shown to be significant determinants
      for diabetes.

PMID- 24564931
TI  - Public health human resources: a comparative analysis of policy documents in two
      Canadian provinces.
AB  - BACKGROUND: Amidst concerns regarding the capacity of the public health system to
      respond rapidly and appropriately to threats such as pandemics and terrorism,
      along with changing population health needs, governments have focused on
      strengthening public health systems. A key factor in a robust public health
      system is its workforce. As part of a nationally funded study of public health
      renewal in Canada, a policy analysis was conducted to compare public health human
      resources-relevant documents in two Canadian provinces, British Columbia (BC) and
      Ontario (ON), as they each implement public health renewal activities. METHODS: A
      content analysis of policy and planning documents from government and public
      health-related organizations was conducted by a research team comprised of
      academics and government decision-makers. Documents published between 2003 and
      2011 were accessed (BC = 27; ON = 20); documents were either publicly available
      or internal to government and excerpted with permission. Documentary texts were
      deductively coded using a coding template developed by the researchers based on
      key health human resources concepts derived from two national policy documents.
      RESULTS: Documents in both provinces highlighted the importance of public health
      human resources planning and policies; this was particularly evident in early
      post-SARS documents. Key thematic areas of public health human resources
      identified were: education, training, and competencies; capacity; supply;
      intersectoral collaboration; leadership; public health planning context; and
      priority populations. Policy documents in both provinces discussed the importance
      of an educated, competent public health workforce with the appropriate skills and
      competencies for the effective and efficient delivery of public health services.
      CONCLUSION: This policy analysis identified progressive work on public health
      human resources policy and planning with early documents providing an inventory
      of issues to be addressed and later documents providing evidence of beginning
      policy development and implementation. While many similarities exist between the
      provinces, the context distinctive to each province has influenced and shaped how
      they have focused their public health human resources policies.

PMID- 24564930
TI  - Capturing changes in dietary patterns among older adults: a latent class analysis
      of an ageing Irish cohort.
AB  - OBJECTIVE: Data-driven approaches to dietary patterns are under-utilized; latent
      class analyses (LCA) are particularly rare. The present study used an LCA to
      identify subgroups of people with similar dietary patterns, explore changes in
      dietary patterns over a 10-year period and relate these dynamics to
      sociodemographic factors and health outcomes. DESIGN: The 1998 baseline and 2008
      follow-up of the Cork and Kerry Diabetes and Heart Disease Study. Diets were
      assessed with a standard FFQ. LCA, under the assumption of conditional
      independence, was used to identify mutually exclusive subgroups with different
      dietary patterns, based on food group consumption. SETTING: Republic of Ireland.
      SUBJECTS: Men and women aged 50-69 years at baseline (n 923) and at 10-year
      follow-up (n 320). RESULTS: Three dietary classes emerged: Western, Healthy and
      Low-Energy. Significant differences in demographic, lifestyle and health outcomes
      were associated with class membership. Between baseline and follow-up most people
      remained 'stable' in their dietary class. Most of those who changed class moved
      to the Healthy class. Higher education was associated with transition to a
      healthy diet; lower education was associated with stability in an unhealthy
      pattern. Transition to a healthy diet was associated with higher CVD risk factors
      at baseline: respondents were significantly more likely to be smokers, centrally
      obese and to have hypertension (non-significant). CONCLUSIONS: LCA is useful for
      exploring dietary patterns transitions. Understanding the predictors of
      longitudinal stability/transitions in dietary patterns will help target public
      health initiatives by identifying subgroups most/least likely to change and
      most/least likely to sustain a change.

PMID- 24564932
TI  - Evaluating the quality of informed consent and contemporary clinical practices by
      medical doctors in South Africa: an empirical study.
AB  - BACKGROUND: Informed consent is a legal and ethical doctrine derived from the
      principle of respect for autonomy. Generally two rights derived from autonomy are
      accorded legal protection. The constitutional right to bodily integrity followed
      by the right to bodily well-being, protected by professional negligence rules.
      Therefore healthcare professionals treating patients' without valid consent may
      be guilty of infringing patients' rights. Many challenges are experienced by
      doctors obtaining informed consent in complex multicultural societies like South
      Africa. These include different cultural ethos, multilingualism, poverty,
      education, unfamiliarity with libertarian rights based autonomy, and power
      asymmetry between doctors and patients. All of which could impact on the ability
      of doctors to obtain legally valid informed consent. METHODS: The objective of
      this study was to evaluate whether the quality of informed consent obtained by
      doctors practicing in South Africa is consistent with international ethical
      standards and local regulations. Responses from 946 participants including
      doctors, nurses and patients was analyzed, using a semi-structured self
      administered questionnaire and person triangulation in selected public hospitals
      in Durban, KwaZulu-Natal, South Africa. RESULTS: The median age of 168 doctors
      participating was 30 years with 51% females, 28% interns, 16% medical officers,
      26% registrars, 30% consultant/specialists. A broad range of clinical specialties
      were represented. Challenges to informed consent practice include language
      difficulties, lack of interpreters, workload, and time constraints. Doctors spent
      5-10 minutes on consent, disclosed most information required to patients, however
      knowledge of essential local laws was inadequate. Informed consent aggregate
      scores (ICAS) showed that interns/registrars scored lower than
      consultants/specialists. ICAS scores were statistically significant by specialty
      (p = 0.005), with radiologists and anaesthetists scoring lowest, while
      internists, GPs and obstetricians/gynaecologists scored highest. Comparative ICAS
      scores showed that professional nurses scored significantly lower than doctors (p
      <= 0.001). CONCLUSIONS: This study shows that though doctors had general
      knowledge of informed consent requirements, execution in practice was inadequate,
      with deficiency in knowledge of basic local laws and regulations. Remedying
      identified deficiencies may require a 'corps' of interpreters in local hospitals
      to assist doctors in dealing with language difficulties, and continuing education
      in medical law and ethics to improve informed consent practices and overall
      quality of healthcare service delivery.

PMID- 24564933
TI  - The separate impact of tight control schemes and disease activity on quality of
      life in patients with early rheumatoid arthritis: results from the CAMERA trials.
AB  - OBJECTIVES: To examine in patients with early rheumatoid arthritis (RA) whether
      quality of life (QoL), independently of disease activity, is affected by tight
      control treatment strategy schemes. METHODS: In the Computer Assisted Management
      in Early RA (CAMERA) trials, patients with early RA, disease duration <1 year, no
      prior use of DMARDs) had been randomised to a methotrexate (MTX)-based tight
      control strategy or usual care (CAMERA study) or to 10 mg/d prednisone or placebo
      both added from start to a MTX-based tight control strategy (CAMERA-II study). In
      either study, randomisation to the more intensive strategy resulted in lower
      disease activity. To assess QoL, the 'Influence of Rheumatic Diseases on General
      Health and Lifestyle' questionnaire (IRGL) was used. Baseline and 1- and/or 2
      year measurements were analysed with regression analyses with the IRGL
      (sub)scales as outcome variables and treatment strategy and disease activity
      assessing 28 joints (DAS28) as independent variables, correcting for baseline
      values of each scale and possible confounders (gender, age, rheumatoid factor
      status). RESULTS: There was no clear association between either of the treatment
      strategies and QoL, but a decrease in DAS28 was associated with improvement in
      the majority of QoL (sub)scales. CONCLUSIONS: No independent effect of the
      specific tight control strategies schemes on QoL was found, while there was a
      clear disease activity related effect. Thus frequent outpatient visits or the
      inclusion of prednisone in a tight control strategy did not negatively influence
      QoL.

PMID- 24564934
TI  - An aggregate analysis of many predicted structures to reduce errors in protein
      structure comparison caused by conformational flexibility.
AB  - BACKGROUND: Conformational flexibility creates errors in the comparison of
      protein structures. Even small changes in backbone or sidechain conformation can
      radically alter the shape of ligand binding cavities. These changes can cause
      structure comparison programs to overlook functionally related proteins with
      remote evolutionary similarities, and cause others to incorrectly conclude that
      closely related proteins have different binding preferences, when their
      specificities are actually similar. Towards the latter effort, this paper applies
      protein structure prediction algorithms to enhance the classification of
      homologous proteins according to their binding preferences, despite radical
      conformational differences. METHODS: Specifically, structure prediction
      algorithms can be used to "remodel" existing structures against the same
      template. This process can return proteins in very different conformations to
      similar, objectively comparable states. Operating on close homologs exploits the
      accuracy of structure predictions on closely related proteins, but structure
      prediction is often a nondeterministic process. Identical inputs can generate
      subtly different models with very different binding cavities that make structure
      comparison difficult. We present a first method to mitigate such errors, called
      "medial remodeling", that examines a large number of predicted structures to
      eliminate extreme models of the same binding cavity. RESULTS: Our results, on the
      enolase and tyrosine kinase superfamilies, demonstrate that remodeling can enable
      proteins in very different conformations to be returned to states that can be
      objectively compared. Structures that would have been erroneously classified as
      having different binding preferences were often correctly classified after
      remodeling, while structures that would have been correctly classified as having
      different binding preferences almost always remained distinct. The enolase
      superfamily, which exhibited less sequential diversity than the tyrosine kinase
      superfamily, was classified more accurately after remodeling than the tyrosine
      kinases. Medial remodeling reduced errors from models with unusual perturbations
      that distort the shape of the binding site, enhancing classification accuracy.
      CONCLUSIONS: This paper demonstrates that protein structure prediction can
      compensate for conformational variety in the comparison of protein-ligand binding
      sites. While protein structure prediction introduces new uncertainties into the
      structure comparison problem, our results indicate that unusual models can be
      ignored through an analysis of many models, using techniques like medial
      remodeling. These results point to applications of protein structure comparison
      that extend beyond existing crystal structures.

PMID- 24564935
TI  - Peptide identification based on fuzzy classification and clustering.
AB  - BACKGROUND: The sequence database searching has been the dominant method for
      peptide identification, in which a large number of peptide spectra generated from
      LC/MS/MS experiments are searched using a search engine against theoretical
      fragmentation spectra derived from a protein sequences database or a spectral
      library. Selecting trustworthy peptide spectrum matches (PSMs) remains a
      challenge. RESULTS: A novel scoring method named FC-Ranker is developed to assign
      a nonnegative weight to each target PSM based on the possibility of its being
      correct. Particularly, the scores of PSMs are updated by using a fuzzy SVM
      classification model and a fuzzy silhouette index iteratively. Trustworthy PSMs
      will be assigned high scores when the algorithm stops. CONCLUSIONS: Our
      experimental studies show that FC-Ranker outperforms other post-database search
      algorithms over a variety of datasets, and it can be extended to solve a general
      classification problem with uncertain labels.

PMID- 24564936
TI  - Neuropathology of the posteroinferior occipitotemporal gyrus in children with
      autism.
AB  - BACKGROUND: While most neuropathologic studies focus on regions involved in
      behavioral abnormalities in autism, it is also important to identify whether
      areas that appear functionally normal are devoid of pathologic alterations. In
      this study we analyzed the posteroinferior occipitotemporal gyrus, an
      extrastriate area not considered to be affected in autism. This area borders the
      fusiform gyrus, which is known to exhibit functional and cellular abnormalities
      in autism. FINDINGS: No studies have implicated posteroinferior occipitotemporal
      gyrus dysfunction in autism, leading us to hypothesize that neuropathology would
      not occur in this area. We indeed observed no significant differences in
      pyramidal neuron number or size in layers III, V, and VI in seven pairs of autism
      and controls. CONCLUSIONS: These findings are consistent with the hypothesis that
      neuropathology is unique to areas involved in stereotypies and social and
      emotional behaviors, and support the specificity of the localization of pathology
      in the fusiform gyrus.

PMID- 24564937
TI  - Muscovy duck reovirus p10.8 protein localizes to the nucleus via a
      nonconventional nuclear localization signal.
AB  - BACKGROUND: It was previously report that the first open reading frame of Muscovy
      duck reocvirus S4 gene encodes a 95-amino-acid protein, designed p10.8, which has
      no sequence similarity to other known proteins. Its amino acid sequence offers no
      clues about its function. RESULTS: Subcellular localization and nuclear import
      signal of p10.8 were characterized. We found that p10.8 protein localizes to the
      nucleus of infected and transfected cells, suggesting that p10.8 nuclear
      localization is not facilitated by viral infection or any other viral protein. A
      functional non-canonical nuclear localization signal (NLS) for p10.8 was
      identified and mapped to N-terminus residues 1-40. The NLS has the ability to
      retarget a large cytoplasmic protein to the nucleus. CONCLUSIONS: p10.8 imported
      into the nucleus might via a nonconventional signal nuclear signal.

PMID- 24564938
TI  - Human enteroids: preclinical models of non-inflammatory diarrhea.
AB  - Researchers need an available and easy-to-use model of the human intestine to
      better understand human intestinal physiology and pathophysiology of diseases,
      and to offer an enhanced platform for developing drug therapy. Our work employs
      human enteroids derived from each of the major intestinal sections to advance
      understanding of several diarrheal diseases, including those caused by cholera,
      rotavirus and enterohemorrhagic Escherichia coli. An enteroid bank is being
      established to facilitate comparison of segmental, developmental, and regulatory
      differences in transport proteins that can influence therapy efficacy. Basic
      characterization of major ion transport protein expression, localization and
      function in the human enteroid model sets the stage to study the effects of
      enteric infection at the transport level, as well as to monitor potential
      responses to pharmacological intervention. 

PMID- 24564939
TI  - mAPC-GibbsOS: an integrated approach for robust identification of gene regulatory
      networks.
AB  - BACKGROUND: Identification of cooperative gene regulatory network is an important
      topic for biological study especially in cancer research. Traditional approaches
      suffer from large noise in gene expression data and false positive connections in
      motif binding data; they also fail to identify the modularized structure of gene
      regulatory network. Methods that are capable of revealing underlying modularized
      structure and robust to noise and false positives are needed to be developed.
      RESULTS: We proposed and developed an integrated approach to identify gene
      regulatory networks, which consists of a novel clustering method (namely motif
      guided affinity propagation clustering (mAPC)) and a sampling based method
      (called Gibbs sampler based on outlier sum statistic (GibbsOS)). mAPC is used in
      the first step to obtain co-regulated gene modules by clustering genes with a
      similarity measurement taking into account both gene expression data and binding
      motif information. This clustering method can reduce the noise effect from
      microarray data to obtain modularized gene clusters. However, due to many false
      positives in motif binding data, some genes not regulated by certain
      transcription factors (TFs) will be falsely clustered with true target genes. To
      overcome this problem, GibbsOS is applied in the second step to refine each
      cluster for the identification of true target genes. In order to evaluate the
      performance of the proposed method, we generated simulation data under different
      signal-to-noise ratios and false positive ratios to test the method. The
      experimental results show an improved accuracy in terms of clustering and
      transcription factor identification. Moreover, an improved performance is
      demonstrated in target gene identification as compared with GibbsOS. Finally, we
      applied the proposed method to two breast cancer patient datasets to identify
      cooperative transcriptional regulatory networks associated with recurrence of
      breast cancer, as supported by their functional annotations. CONCLUSIONS: We have
      developed a two-step approach for gene regulatory network identification,
      featuring an integrated method to identify modularized regulatory structures and
      refine their target genes subsequently. Simulation studies have shown the
      robustness of the method against noise in gene expression data and false
      positives in motif binding data. The proposed method has been applied to two
      breast cancer gene expression datasets to infer the hidden regulation mechanisms.
      The experimental results demonstrate the efficacy of the method in identifying
      key regulatory networks related to the progression and recurrence of breast
      cancer.

PMID- 24564941
TI  - Stringent DDI-based prediction of H. sapiens-M. tuberculosis H37Rv protein
      protein interactions.
AB  - BACKGROUND: H. sapiens-M. tuberculosis H37Rv protein-protein interaction (PPI)
      data are very important information to illuminate the infection mechanism of M.
      tuberculosis H37Rv. But current H. sapiens-M. tuberculosis H37Rv PPI data are
      very scarce. This seriously limits the study of the interaction between this
      important pathogen and its host H. sapiens. Computational prediction of H.
      sapiens-M. tuberculosis H37Rv PPIs is an important strategy to fill in the gap.
      Domain-domain interaction (DDI) based prediction is one of the frequently used
      computational approaches in predicting both intra-species and inter-species PPIs.
      However, the performance of DDI-based host-pathogen PPI prediction has been
      rather limited. RESULTS: We develop a stringent DDI-based prediction approach
      with emphasis on (i) differences between the specific domain sequences on
      annotated regions of proteins under the same domain ID and (ii) calculation of
      the interaction strength of predicted PPIs based on the interacting residues in
      their interaction interfaces. We compare our stringent DDI-based approach to a
      conventional DDI-based approach for predicting PPIs based on gold standard intra
      species PPIs and coherent informative Gene Ontology terms assessment. The
      assessment results show that our stringent DDI-based approach achieves much
      better performance in predicting PPIs than the conventional approach. Using our
      stringent DDI-based approach, we have predicted a small set of reliable H.
      sapiens-M. tuberculosis H37Rv PPIs which could be very useful for a variety of
      related studies. We also analyze the H. sapiens-M. tuberculosis H37Rv PPIs
      predicted by our stringent DDI-based approach using cellular compartment
      distribution analysis, functional category enrichment analysis and pathway
      enrichment analysis. The analyses support the validity of our prediction result.
      Also, based on an analysis of the H. sapiens-M. tuberculosis H37Rv PPI network
      predicted by our stringent DDI-based approach, we have discovered some important
      properties of domains involved in host-pathogen PPIs. We find that both host and
      pathogen proteins involved in host-pathogen PPIs tend to have more domains than
      proteins involved in intra-species PPIs, and these domains have more interaction
      partners than domains on proteins involved in intra-species PPI. CONCLUSIONS: The
      stringent DDI-based prediction approach reported in this work provides a
      stringent strategy for predicting host-pathogen PPIs. It also performs better
      than a conventional DDI-based approach in predicting PPIs. We have predicted a
      small set of accurate H. sapiens-M. tuberculosis H37Rv PPIs which could be very
      useful for a variety of related studies.

PMID- 24564942
TI  - Boolean genetic network model for the control of C. elegans early embryonic cell
      cycles.
AB  - BACKGROUND: In Caenorhabditis elegans early embryo, cell cycles only have two
      phases: DNA synthesis and mitosis, which are different from the typical 4-phase
      cell cycle. Modeling this cell-cycle process into network can fill up the gap in
      C. elegans cell-cycle study and provide a thorough understanding on the cell
      cycle regulations and progressions at the network level. METHODS: In this paper,
      C. elegans early embryonic cell-cycle network has been constructed based on the
      knowledge of key regulators and their interactions from literature studies. A
      discrete dynamical Boolean model has been applied in computer simulations to
      study dynamical properties of this network. The cell-cycle network is compared
      with random networks and tested under several perturbations to analyze its
      robustness. To investigate whether our proposed network could explain biological
      experiment results, we have also compared the network simulation results with
      gene knock down experiment data. RESULTS: With the Boolean model, this study
      showed that the cell-cycle network was stable with a set of attractors (fixed
      points). A biological pathway was observed in the simulation, which corresponded
      to a whole cell-cycle progression. The C. elegans network was significantly
      robust when compared with random networks of the same size because there were
      less attractors and larger basins than random networks. Moreover, the network was
      also robust under perturbations with no significant change of the basin size. In
      addition, the smaller number of attractors and the shorter biological pathway
      from gene knock down network simulation interpreted the shorter cell-cycle
      lengths in mutant from the RNAi gene knock down experiment data. Hence, we
      demonstrated that the results in network simulation could be verified by the RNAi
      gene knock down experiment data. CONCLUSIONS: A C. elegans early embryonic cell
      cycles network was constructed and its properties were analyzed and compared with
      those of random networks. Computer simulation results provided biologically
      meaningful interpretations of RNAi gene knock down experiment data.

PMID- 24564944
TI  - Multi-task feature selection in microarray data by binary integer programming.
AB  - A major challenge in microarray classification is that the number of features is
      typically orders of magnitude larger than the number of examples. In this paper,
      we propose a novel feature filter algorithm to select the feature subset with
      maximal discriminative power and minimal redundancy by solving a quadratic
      objective function with binary integer constraints. To improve the computational
      efficiency, the binary integer constraints are relaxed and a low-rank
      approximation to the quadratic term is applied. The proposed feature selection
      algorithm was extended to solve multi-task microarray classification problems. We
      compared the single-task version of the proposed feature selection algorithm with
      9 existing feature selection methods on 4 benchmark microarray data sets. The
      empirical results show that the proposed method achieved the most accurate
      predictions overall. We also evaluated the multi-task version of the proposed
      algorithm on 8 multi-task microarray datasets. The multi-task feature selection
      algorithm resulted in significantly higher accuracy than when using the single
      task feature selection methods. 

PMID- 24564943
TI  - Eptifibatide-induced acute profound thrombocytopenia: a case report.
AB  - BACKGROUND: The interactions among cells or among cells and components of the
      extracellular matrix, is a crucial pathophysiological process involving some
      molecules collectively known as adhesion molecules (CAMs). Glycoprotein IIb /
      IIIa receptors are only restricted to blood platelets and they bind fibrinogen
      and adhesion proteins such as fibronectin, vitronectin, von Willebrand factor to
      form cross bridges between adjacent platelets. IIb/IIIa receptor antagonists are
      an object of intense research activity for target therapy worldwide during the
      last decades. Three GPIIb/IIIa inhibitors, abciximab, tirofiban, and
      eptifibatide, have been approved for clinical use. Profound thrombocytopenia is
      an uncommon but clinically important complication of glycoprotein IIb/IIIa
      inhibitors. CASE PRESENTATION: This case report discusses a forty-four-year-old
      male patient with acute coronary syndrome who underwent percutaneous coronary
      intervention and developed profound thrombocytopenia within 4 hours of first
      administration of eptifibatide. CONCLUSION: This report adds another case of
      eptifibatide-induced thrombocytopenia to the medical literature and endorses the
      importance of platelet count monitoring after initiating therapy with this agent.

PMID- 24564945
TI  - SPIC: a novel similarity metric for comparing transcription factor binding site
      motifs based on information contents.
AB  - BACKGROUND: Discovering transcription factor binding sites (TFBS) is one of
      primary challenges to decipher complex gene regulatory networks encrypted in a
      genome. A set of short DNA sequences identified by a transcription factor (TF) is
      known as a motif, which can be expressed accurately in matrix form such as a
      position-specific scoring matrix (PSSM) and a position frequency matrix. Very
      frequently, we need to query a motif in a database of motifs by seeking its
      similar motifs, merge similar TFBS motifs possibly identified by the same TF,
      separate irrelevant motifs, or filter out spurious motifs. Therefore, a novel
      metric is required to seize slight differences between irrelevant motifs and
      highlight the similarity between motifs of the same group in all these
      applications. While there are already several metrics for motif similarity
      proposed before, their performance is still far from satisfactory for these
      applications. METHODS: A novel metric has been proposed in this paper with name
      as SPIC (Similarity with Position Information Contents) for measuring the
      similarity between a column of a motif and a column of another motif. When
      defining this similarity score, we consider the likelihood that the column of the
      first motif's PFM can be produced by the column of the second motif's PSSM, and
      multiply the likelihood by the information content of the column of the second
      motif's PSSM, and vise versa. We evaluated the performance of SPIC combined with
      a local or a global alignment method having a function for affine gap penalty,
      for computing the similarity between two motifs. We also compared SPIC with seven
      existing state-of-the-arts metrics for their capability of clustering motifs from
      the same group and retrieving motifs from a database on three datasets. RESULTS:
      When used jointly with the Smith-Waterman local alignment method with an affine
      gap penalty function (gap open penalty is equal to 1, gap extension penalty is
      equal to 0.5), SPIC outperforms the seven existing state-of-the-art motif
      similarity metrics combined with their best alignments for matching motifs in
      database searches, and clustering the same TF's sub-motifs or distinguishing
      relevant ones from a miscellaneous group of motifs. CONCLUSIONS: We have
      developed a novel motif similarity metric that can more accurately match motifs
      in database searches, and more effectively cluster similar motifs and
      differentiate irrelevant motifs than do the other seven metrics we are aware of.

PMID- 24564946
TI  - Endothelial function, arterial wall mechanics and intima media thickness in
      juvenile idiopathic arthritis.
AB  - OBJECTIVES: Juvenile idiopathic arthritis (JIA) is a chronic inflammatory disease
      of children which might persist into adulthood. Systemic inflammation seen in
      adult RA patients has been shown to be associated with alteration in endothelial
      function, arterial wall mechanics and intima media thickness. Our study was
      planned to assess similar changes in JIA patients. METHODS: Thirty-one newly
      diagnosed JIA patients and a similar number of age- and sex-matched controls were
      enrolled in the study. Endothelial function was assessed by measuring flow
      mediated dilation and glyceryl trinitrate (GTN)-mediated dilation of the brachial
      artery. To assess arterial stiffness, various arterial wall mechanic parameters
      such as cross-sectional compliance, cross-sectional distensibility, shear stress
      and elastic modulus were derived. Intima media thickness of the common carotid
      artery was measured as a marker of subclinical atherosclerosis. RESULTS: The
      brachial artery diameter at rest was found to be slightly lower in the patients
      than controls (0.258 +/- 0.042 vs. 0.264 +/- 0.039; p=0.54). No significant
      difference was found in flow mediated dilation (17.71 +/- 9.26 vs. 16.31 +/-
      8.23; p=0.53), GTN mediated dilation (25.25 +/- 10.02 vs. 23.66 +/- 9.79; p=0.53)
      or FMD: GTN mediated dilation ratio (0.730 +/- 0.432 vs. 0.717 +/- 0.280; p=0.89)
      between the cases and controls. There was also no significant difference in
      carotid artery intima media thickness (0.065 +/- 0.0068 vs. 0.068 +/- 0.007;
      p=0.084) between cases and controls. Cases in different subsets of JIA were also
      analysed separately with regards to FMD, GTN mediated dilation and cIMT but no
      difference was found between cases in each subset and their controls. Cross
      sectional compliance was significantly lower in cases than controls (0.0016 +/-
      0.0005 vs. 0.002 +/- 0.001; p=0.034). Cross-sectional distensibility (0.009 +/-
      0.003 vs. 0.011 +/- 0.006; p=0.14) was also found to be lower whereas diastolic
      wall shear stress (299.9 +/- 47.08 vs. 294.9 +/- 59.5; p=0.72) and elastic
      modulus (1138.5 +/- 1085.8 vs. 911 +/- 453; p=0.19) were found to be higher in
      cases as compared to controls. But these differences were not statistically
      significant. When the subsets were analysed separately for vessel wall indices,
      cross-sectional compliance was found to be significantly lower in systemic
      arthritis patients as compared to controls. A high level of intra- and inter
      observer agreement was found for all the ultrasonographically evaluated
      parameters. CONCLUSIONS: Arterial wall indices were found altered in JIA patients
      indicating increased arterial stiffness. Larger studies are required to assess
      endothelial dysfunction, intima media thickness and arterial stiffness in each
      subset of JIA patients.

PMID- 24564947
TI  - Soluble factors secreted by differentiating embryonic stem cells stimulate
      exogenous cell proliferation and migration.
AB  - INTRODUCTION: Stem cells are being investigated as catalysts of tissue
      regeneration to either directly replace or promote cellularity lost as a result
      of traumatic injury or degenerative disease. In many reports, despite low numbers
      of stably integrated cells, the transient presence of cells delivered or
      recruited to sites of tissue remodeling globally benefits functional recovery.
      Such findings have motivated the need to determine how paracrine factors secreted
      from transplanted cells may be capable of positively impacting endogenous repair
      processes and somatic cell responses. METHODS: Embryonic stem cells were
      differentiated as embryoid bodies (EBs) in vitro and media conditioned by EBs
      were collected at different intervals of time. Gene and protein expression
      analysis of several different growth factors secreted by EBs were examined by
      polymerase chain reaction and enzyme-linked immunosorbent assay analysis,
      respectively, as a function of time. The proliferation and migration of
      fibroblasts and endothelial cells treated with EB conditioned media was examined
      compared with unconditioned and growth media controls. RESULTS: The expression of
      several growth factors, including bone morphogenic protein-4, insulin-like growth
      factors and vascular endothelial growth factor-A, increased during the course of
      embryonic stem cell (ESC) differentiation as EBs. Conditioned media collected
      from EBs at different stages of differentiation stimulated proliferation and
      migration of both fibroblasts and endothelial cells, based on 5-bromo-2'
      deoxyuridine incorporation and transwell assays, respectively. CONCLUSIONS:
      Overall, these results demonstrate that differentiating ESCs express increasing
      amounts of various growth factors over time that altogether are capable of
      stimulating mitogenic and motogenic activity of exogenous cell populations.

PMID- 24564948
TI  - Study participants incentives, compensation and reimbursement in resource
      constrained settings.
AB  - INTRODUCTION: Controversies still exists within the research fraternity on the
      form and level of incentives, compensation and reimbursement to study
      participants in resource-constrained settings. While most research activities
      contribute significantly to advancement of mankind, little has been considered in
      rewarding directly the research participants from resource-constrained areas.
      METHODS: A study was conducted in Zimbabwe to investigate views and expectations
      of various stakeholders on study participation incentives, compensation and
      reimbursement issues. Data was collected using various methods including a survey
      of about 1,008 parents/guardians of school children participating in various
      immunological cohort studies and parasitology surveys. Community advisory boards
      (CABs) at 9 of the sites were also consulted. Further, information was gathered
      during discussions held at a basic research ethics training workshop. The
      workshop had 45 participants that including 40 seasoned Zimbabwean researchers
      and 5 international research collaborators. RESULTS: About 90% (907) of the study
      participants and guardians expected compensation of reasonable value, in view of
      the researchers' value and comparison to other sites regardless of economic
      status of the community. During discussion with researchers at a basic ethics
      training workshop, about 80% (32) believed that decisions on level of
      compensation should be determined by the local research ethics committees. While,
      the few international research collaborators were of the opinion that
      compensation should be in accordance with local guidelines, and incentives should
      be in line with funding. Both the CAB members and study participants expressed
      that there should be a clear distinction between study incentive and compensation
      accorded to individual and community expectations on benefits from studies.
      However, CABs expressed that their suggestions on incentives and compensation are
      often moderated by the regulatory authorities who cite fear of unknown concerns.
      CONCLUSION: Overall, both personal and community benefits need to be considered
      collectively in future studies to be conducted in resource-constrained
      communities. There is projected fear that recruitment in future may be a
      challenge, now that almost every community, has somehow been reached and
      participated in some form of studies. A major concern on reimbursement,
      compensation or incentives should be internationally pegged regardless of
      different economic status of the individuals or communities where the study is to
      be conducted.

PMID- 24564950
TI  - Role of Waddlia chondrophila placental infection in miscarriage.
AB  - Waddlia chondrophila is an intracellular bacterium suspected to cause human and
      bovine abortion. We confirmed an association between antibodies against W.
      chondrophila and human miscarriage and identified this organism in placenta or
      genital tract of women who had had miscarriages. These results suggest a possible
      role of W. chondrophila infection in miscarriage. 

PMID- 24564951
TI  - Casting materials and their application in research and teaching.
AB  - From a biological point of view, casting refers to filling of anatomical and/or
      pathological spaces with extraneous material that reproduces a three-dimensional
      replica of the space. Casting may be accompanied by additional procedures such as
      corrosion, in which the soft tissue is digested out, leaving a clean cast, or the
      material may be mixed with radiopaque substances to allow x-ray photography or
      micro computed topography (uCT) scanning. Alternatively, clearing of the
      surrounding soft tissue increases transparency and allows visualization of the
      casted cavities. Combination of casting with tissue fixation allows anatomical
      dissection and didactic surgical procedures on the tissue. Casting materials fall
      into three categories namely, aqueous substances (India ink, Prussian blue ink),
      pliable materials (gelatins, latex, and silicone rubber), or hard materials
      (methyl methacrylates, polyurethanes, polyesters, and epoxy resins). Casting has
      proved invaluable in both teaching and research and many phenomenal biological
      processes have been discovered through casting. The choice of a particular
      material depends inter alia on the targeted use and the intended subsequent
      investigative procedures, such as dissection, microscopy, or uCT. The casting
      material needs to be pliable where anatomical and surgical manipulations are
      intended, and capillary-passable for ultrastructural investigations. 

PMID- 24564949
TI  - Levels and patterns of objectively-measured physical activity volume and
      intensity distribution in UK adolescents: the ROOTS study.
AB  - BACKGROUND: Few studies have quantified levels of habitual physical activity
      across the entire intensity range. We aimed to describe variability in total and
      intensity-specific physical activity levels in UK adolescents across gender,
      socio-demographic, temporal and body composition strata. METHODS: Physical
      activity energy expenditure and minutes per day (min/d) spent sedentary and in
      light, moderate, and vigorous intensity physical activity were assessed in 825
      adolescents from the ROOTS study (43.5% boys; mean age 15.0 +/- 0.30 years), by 4
      days of individually calibrated combined heart rate and movement sensing.
      Measurement days were classified as weekday or weekend and according to the three
      school terms: summer (April-July), autumn (September-December), and spring
      (January-March). Gender and age were self-reported and area-level SES determined
      by postcode data. Body composition was measured by anthropometry and bio
      electrical impedance. Variability in physical activity and sedentary time was
      analysed by linear multilevel modelling, and logistic multilevel regression was
      used to determine factors associated with physical inactivity (<60 min moderate
      to-vigorous intensity physical activity/d). RESULTS: During awake hours (15.8 +/-
      0.9 hrs/d), adolescents primarily engaged in light intensity physical activity
      (517 min/d) and sedentary time (364 min/d). Boys were consistently more
      physically active and less sedentary than girls, but gender differences were
      smaller at weekends, as activity levels in boys dropped more markedly when
      transitioning from weekday to weekend. Boys were more sedentary on both weekend
      days compared to during the week, whereas girls were more sedentary on Sunday but
      less sedentary on Saturday. In both genders light intensity physical activity was
      lower in spring, while moderate physical activity was lower in autumn and spring
      terms, compared to the summer term; sedentary time was also higher in spring than
      summer term. Adolescents with higher fatness engaged in less vigorous intensity
      physical activity. Factors associated with increased odds of physical inactivity
      were female gender, both weekend days in boys, and specifically Sunday in girls.
      CONCLUSIONS: Physical activity components vary by gender, temporal factors and
      body composition in UK adolescents. The available data indicate that in
      adolescence, girls should be the primary targets of interventions designed to
      increase physical activity levels.

PMID- 24564952
TI  - DINC: a new AutoDock-based protocol for docking large ligands.
AB  - BACKGROUND: Using the popular program AutoDock, computer-aided docking of small
      ligands with 6 or fewer rotatable bonds, is reasonably fast and accurate.
      However, docking large ligands using AutoDock's recommended standard docking
      protocol is less accurate and computationally slow. RESULTS: In our earlier work,
      we presented a novel AutoDock-based incremental protocol (DINC) that addresses
      the limitations of AutoDock's standard protocol by enabling improved docking of
      large ligands. Instead of docking a large ligand to a target protein in one
      single step as done in the standard protocol, our protocol docks the large ligand
      in increments. In this paper, we present three detailed examples of docking using
      DINC and compare the docking results with those obtained using AutoDock's
      standard protocol. We summarize the docking results from an extended docking
      study that was done on 73 protein-ligand complexes comprised of large ligands. We
      demonstrate not only that DINC is up to 2 orders of magnitude faster than
      AutoDock's standard protocol, but that it also achieves the speed-up without
      sacrificing docking accuracy. We also show that positional restraints can be
      applied to the large ligand using DINC: this is useful when computing a docked
      conformation of the ligand. Finally, we introduce a webserver for docking large
      ligands using DINC. CONCLUSIONS: Docking large ligands using DINC is
      significantly faster than AutoDock's standard protocol without any loss of
      accuracy. Therefore, DINC could be used as an alternative protocol for docking
      large ligands. DINC has been implemented as a webserver and is available at
      http://dinc.kavrakilab.org. Applications such as therapeutic drug design,
      rational vaccine design, and others involving large ligands could benefit from
      DINC and its webserver implementation.

PMID- 24564953
TI  - Toward a 3D model of human brain development for studying gene/environment
      interactions.
AB  - This project aims to establish and characterize an in vitro model of the
      developing human brain for the purpose of testing drugs and chemicals. To
      accurately assess risk, a model needs to recapitulate the complex interactions
      between different types of glial cells and neurons in a three-dimensional
      platform. Moreover, human cells are preferred over cells from rodents to
      eliminate cross-species differences in sensitivity to chemicals. Previously, we
      established conditions to culture rat primary cells as three-dimensional
      aggregates, which will be humanized and evaluated here with induced pluripotent
      stem cells (iPSCs). The use of iPSCs allows us to address gene/environment
      interactions as well as the potential of chemicals to interfere with epigenetic
      mechanisms. Additionally, iPSCs afford us the opportunity to study the effect of
      chemicals during very early stages of brain development. It is well recognized
      that assays for testing toxicity in the developing brain must consider
      differences in sensitivity and susceptibility that arise depending on the time of
      exposure. This model will reflect critical developmental processes such as
      proliferation, differentiation, lineage specification, migration, axonal growth,
      dendritic arborization and synaptogenesis, which will probably display
      differences in sensitivity to different types of chemicals. Functional endpoints
      will evaluate the complex cell-to-cell interactions that are affected in
      neurodevelopment through chemical perturbation, and the efficacy of drug
      intervention to prevent or reverse phenotypes. The model described is designed to
      assess developmental neurotoxicity effects on unique processes occurring during
      human brain development by leveraging human iPSCs from diverse genetic
      backgrounds, which can be differentiated into different cell types of the central
      nervous system. Our goal is to demonstrate the feasibility of the personalized
      model using iPSCs derived from individuals with neurodevelopmental disorders
      caused by known mutations and chromosomal aberrations. Notably, such a human
      brain model will be a versatile tool for more complex testing platforms and
      strategies as well as research into central nervous system physiology and
      pathology. 

PMID- 24564954
TI  - Epidemiological aspects of HCV infection in non-injecting drug users in the
      Brazilian state of Para, eastern Amazon.
AB  - BACKGROUND: Currently, sharing of drug paraphernalia is the main form of HCV
      transmission worldwide. In South America, consistent findings indicate that
      shared sniffing equipment is an important factor in the spread of HCV among non
      injecting drug users. Epidemiological data on the status of HCV infection in
      illicit drug users in the Amazon region are scarce, although reports of clinical
      cases of hepatitis or pathologies associated with HCV infection in other
      population groups are numerous. Thereby, this study investigated the prevalence,
      genotype frequency, and epidemiological factors associated with HCV infection in
      non-injecting drug users in the state of Para, eastern Amazon. RESULTS: During
      2008-2011, 300 non-injecting drug users attending drug-treatment centers
      participated in this study. Most non-injecting drug users were male (63.7%). The
      mean age was 32.5 years. The non-injecting drugs most consumed were: cannabis
      (15.6%), cocaine paste (21.3%), and oxi cocaine (25.7%). Tobacco (60.9%) and
      alcohol (79.4%) were also commonly consumed. One hundred six (35.1%; CI 95%: 29.8
      - 41.1) non-injecting drug users presented anti-HCV antibodies by EIA. The HCV
      RNA prevalence was 28.0% (95% CI: 20.6 - 35.8). Genotypes 1 (76.9%) and 3 (23.1%)
      of HCV have been identified. A multivariate analysis demonstrated that HCV
      infection was independently associated with the following factors: "age (>= 35
      years)", "tattoos", "use of a needle or syringe sterilized at home", "shared use
      of drug paraphernalia", "uses drugs for more than 5 years", and "use of drugs
      everyday". CONCLUSIONS: This study revealed a high prevalence of HCV infection in
      non-injecting drug users, and most infections are occasioned by genotype 1.
      Likely, HCV transmission is associated with the tattoos, the use of needle or
      syringe sterilized at home by people over the age of 35 years, and sharing, time
      and frequency of use of non-injecting drugs. These findings should serve as an
      incentive for the establishment of a program of Hepatitis C prevention and
      control by the local public-health authorities in order to develop effective
      policies and strategies for contain the spread of HCV infection.

PMID- 24564955
TI  - The role of electrostatic energy in prediction of obligate protein-protein
      interactions.
AB  - BACKGROUND: Prediction and analysis of protein-protein interactions (PPI) and
      specifically types of PPIs is an important problem in life science research
      because of the fundamental roles of PPIs in many biological processes in living
      cells. In addition, electrostatic interactions are important in understanding
      inter-molecular interactions, since they are long-range, and because of their
      influence in charged molecules. This is the main motivation for using
      electrostatic energy for prediction of PPI types. RESULTS: We propose a
      prediction model to analyze protein interaction types, namely obligate and non
      obligate, using electrostatic energy values as properties. The prediction
      approach uses electrostatic energy values for pairs of atoms and amino acids
      present in interfaces where the interaction occurs. The main features of the
      complexes are found and then the prediction is performed via several state-of-the
      art classification techniques, including linear dimensionality reduction (LDR),
      support vector machine (SVM), naive Bayes (NB) and k-nearest neighbor (k-NN). For
      an in-depth analysis of classification results, some other experiments were
      performed by varying the distance cutoffs between atom pairs of interacting
      chains, ranging from 5A to 13A. Moreover, several feature selection algorithms
      including gain ratio (GR), information gain (IG), chi-square (Chi2) and minimum
      redundancy maximum relevance (mRMR) are applied on the available datasets to
      obtain more discriminative pairs of atom types and amino acid types as features
      for prediction. CONCLUSIONS: Our results on two well-known datasets of obligate
      and non-obligate complexes confirm that electrostatic energy is an important
      property to predict obligate and non-obligate protein interaction types on the
      basis of all the experimental results, achieving accuracies of over 98%.
      Furthermore, a comparison performed by changing the distance cutoff demonstrates
      that the best values for prediction of PPI types using electrostatic energy range
      from 9A to 12A, which show that electrostatic interactions are long-range and
      cover a broader area in the interface. In addition, the results on using feature
      selection before prediction confirm that (a) a few pairs of atoms and amino acids
      are appropriate for prediction, and (b) prediction performance can be improved by
      eliminating irrelevant and noisy features and selecting the most discriminative
      ones.

PMID- 24564956
TI  - BRCA-Monet: a breast cancer specific drug treatment mode-of-action network for
      treatment effective prediction using large scale microarray database.
AB  - BACKGROUND: Connectivity map (cMap) is a recent developed dataset and algorithm
      for uncovering and understanding the treatment effect of small molecules on
      different cancer cell lines. It is widely used but there are still remaining
      challenges for accurate predictions. METHOD: Here, we propose BRCA-MoNet, a
      network of drug mode of action (MoA) specific to breast cancer, which is
      constructed based on the cMap dataset. A drug signature selection algorithm
      fitting the characteristic of cMap data, a quality control scheme as well as a
      novel query algorithm based on BRCA-MoNet are developed for more effective
      prediction of drug effects. RESULT: BRCA-MoNet was applied to three independent
      data sets obtained from the GEO database: Estrodial treated MCF7 cell line, BMS
      754807 treated MCF7 cell line, and a breast cancer patient microarray dataset. In
      the first case, BRCA-MoNet could identify drug MoAs likely to share same and
      reverse treatment effect. In the second case, the result demonstrated the
      potential of BRCA-MoNet to reposition drugs and predict treatment effects for
      drugs not in cMap data. In the third case, a possible procedure of personalized
      drug selection is showcased. CONCLUSIONS: The results clearly demonstrated that
      the proposed BRCA-MoNet approach can provide increased prediction power to cMap
      and thus will be useful for identification of new therapeutic candidates.

PMID- 24564957
TI  - Evidence for perennial malaria in rural and urban areas under the Sudanian
      climate of Kandi, Northeastern Benin.
AB  - BACKGROUND: In arid settings, droughts usually lead to periods of very low or no
      malaria transmission. However, in rural Kandi (Sonsoro) in northeastern Benin,
      several malaria cases are often diagnosed during dry seasons. The underlying
      factors accounting for this phenomenon remain unknown. METHODS: The entomological
      profile of Sonsoro has been studied compared to a location in urban Kandi
      (Gansosso) for a period of one year. During this period, Anopheles larval
      habitats were investigated and populations of Anopheles gambiae s.l. were sampled
      by human landing catches in both areas. Enzyme-linked immunosorbent assays
      (ELISA) for Plasmodium falciparum circumsporozoite protein (CSP) were conducted
      on vector specimens and the entomological inoculation rates (EIR) were determined
      per season (wet versus dry) in each area. In addition, during the severe drought
      period, Rapid Diagnostic Tests (RDTs) were conducted on school children under the
      age 10 years in these areas to provide a global view of drought-malaria
      prevalence and to perform a crossing with entomological data in Kandi. RESULTS:
      Overall, An. gambiae s.l. was particularly abundant in rural Kandi compared to
      the urban area with a significant decrease of vector density in both sites during
      the dry season. In this period, larval sampling data identified household water
      sources as potential breeding sites in urban and rural Kandi. We also observed a
      significant seasonal variation of the infectivity rate in both areas but for each
      period (season), the EIR was higher in the rural site than in the urban. Data of
      P. falciparum detection was the reflection of entomological findings. The drought
      malaria prevalence was 5.5 times higher in rural Kandi as compared to urban
      Kandi. The presence of a permanent water site and the low level of urbanization
      in rural Kandi were identified as a risk factor. CONCLUSION: Our data showed a
      high level of malaria transmission in the municipality of Kandi. Household water
      source plays an important role in maintaining the breeding of anopheles larvae
      and the malaria transmission in Kandi. In rural settings, the proximity to
      permanent water sites could probably be the aggravating factor.

PMID- 24564959
TI  - OMACC: an Optical-Map-Assisted Contig Connector for improving de novo genome
      assembly.
AB  - BACKGROUND: Genome sequencing and assembly are essential for revealing the
      secrets of life hidden in genomes. Because of repeats in most genomes, current
      programs collate sequencing data into a set of assembled sequences, called
      contigs, instead of a complete genome. Toward completing a genome, optical
      mapping is powerful in rendering the relative order of contigs on the genome,
      which is called scaffolding. However, connecting the neighboring contigs with
      nucleotide sequences requires further efforts. Nagarajian et al. have recently
      proposed a software module, FINISH, to close the gaps between contigs with other
      contig sequences after scaffolding contigs using an optical map. The results,
      however, are not yet satisfying. RESULTS: To increase the accuracy of contig
      connections, we develop OMACC, which carefully takes into account length
      information in optical maps. Specifically, it rescales optical map and applies
      length constraint for selecting the correct contig sequences for gap closure. In
      addition, it uses an advanced graph search algorithm to facilitate estimating the
      number of repeat copies within gaps between contigs. On both simulated and real
      datasets, OMACC achieves a <10% false gap-closing rate, three times lower than
      the ~27% false rate by FINISH, while maintaining a similar sensitivity.
      CONCLUSION: As optical mapping is becoming popular and repeats are the bottleneck
      of assembly, OMACC should benefit various downstream biological studies via
      accurately connecting contigs into a more complete genome. AVAILABILITY:
      http://140.116.235.124/~tliu/omacc.

PMID- 24564960
TI  - Association between PADI4 gene polymorphisms and anti-cyclic citrullinated
      peptide antibody positive rheumatoid arthritis in a large Chinese Han cohort.
AB  - OBJECTIVES: The present study was undertaken to investigate the association of
      peptidyl-arginine-deiminase type IV gene (PADI4) single nucleotide polymorphisms
      (SNPs) with rheumatoid arthritis (RA) susceptibility, and to determine whether
      there is any impact of PADI4 polymorphisms on RA subsets or phenotypes in a large
      Chinese Han cohort. METHODS: Two PADI4 SNPs (rs2240340 and rs1748033) were
      genotyped in 1216 Chinese Han RA patients and 1040 unaffected controls by TaqMan
      SNP Assays. Serum anti-CCP antibody and anti-PAD4 antibody levels were measured
      by ELISA. Bone destruction was scored by Sharp-van der Heijde scores (SHSs) of
      hands in 463 patients. RESULTS: The two SNPs rs2240340 and rs1748033 of PADI4
      showed strong association with RA susceptibility (OR=1.23, 95% CI 1.09-1.38,
      p=6.66*10-4; and OR=1.24, 95% CI 1.10-1.41, p=6.98*10-4, respectively). RA risk
      genotypes of PADI4 were specifically associated with anti-CCP positive RA
      (rs2240340: p=5.13*10-6; rs1748033: p=2.97*10-3, respectively). Furthermore,
      there was a trend association between PADI4 rs2240340 and radiographic severity,
      though it did not reach the statistic significance (p=0.088). CONCLUSIONS: Our
      data provide strong evidence that PADI4 polymorphisms are risk factors
      contributed to RA susceptibility, especially for anti-CCP positive RA, and may
      confer higher risk of RA radiographic severity in Chinese Han population.

PMID- 24564958
TI  - Variability in the common genetic architecture of social-communication spectrum
      phenotypes during childhood and adolescence.
AB  - BACKGROUND: Social-communication abilities are heritable traits, and their
      impairments overlap with the autism continuum. To characterise the genetic
      architecture of social-communication difficulties developmentally and identify
      genetic links with the autistic dimension, we conducted a genome-wide screen of
      social-communication problems at multiple time-points during childhood and
      adolescence. METHODS: Social-communication difficulties were ascertained at ages
      8, 11, 14 and 17 years in a UK population-based birth cohort (Avon Longitudinal
      Study of Parents and Children; N <= 5,628) using mother-reported Social
      Communication Disorder Checklist scores. Genome-wide Complex Trait Analysis
      (GCTA) was conducted for all phenotypes. The time-points with the highest GCTA
      heritability were subsequently analysed for single SNP association genome-wide.
      Type I error in the presence of measurement relatedness and the likelihood of
      observing SNP signals near known autism susceptibility loci (co-location) were
      assessed via large-scale, genome-wide permutations. Association signals (P <= 10
      5) were also followed up in Autism Genetic Resource Exchange pedigrees (N = 793)
      and the Autism Case Control cohort (Ncases/Ncontrols = 1,204/6,491). RESULTS:
      GCTA heritability was strongest in childhood (h2(8 years) = 0.24) and especially
      in later adolescence (h2(17 years) = 0.45), with a marked drop during early to
      middle adolescence (h2(11 years) = 0.16 and h2(14 years) = 0.08). Genome-wide
      screens at ages 8 and 17 years identified for the latter time-point evidence for
      association at 3p22.2 near SCN11A (rs4453791, P = 9.3 * 10-9; genome-wide
      empirical P = 0.011) and suggestive evidence at 20p12.3 at PLCB1 (rs3761168, P =
      7.9 * 10-8; genome-wide empirical P = 0.085). None of these signals contributed
      to risk for autism. However, the co-location of population-based signals and
      autism susceptibility loci harbouring rare mutations, such as PLCB1, is unlikely
      to be due to chance (genome-wide empirical Pco-location = 0.007). CONCLUSIONS:
      Our findings suggest that measurable common genetic effects for social
      communication difficulties vary developmentally and that these changes may affect
      detectable overlaps with the autism spectrum.

PMID- 24564961
TI  - Development of a brain MRI-based hidden Markov model for dementia recognition.
AB  - BACKGROUND: Dementia is an age-related cognitive decline which is indicated by an
      early degeneration of cortical and sub-cortical structures. Characterizing those
      morphological changes can help to understand the disease development and
      contribute to disease early prediction and prevention. But modeling that can best
      capture brain structural variability and can be valid in both disease
      classification and interpretation is extremely challenging. The current study
      aimed to establish a computational approach for modeling the magnetic resonance
      imaging (MRI)-based structural complexity of the brain using the framework of
      hidden Markov models (HMMs) for dementia recognition. METHODS: Regularity
      dimension and semi-variogram were used to extract structural features of the
      brains, and vector quantization method was applied to convert extracted feature
      vectors to prototype vectors. The output VQ indices were then utilized to
      estimate parameters for HMMs. To validate its accuracy and robustness,
      experiments were carried out on individuals who were characterized as non
      demented and mild Alzheimer's diseased. Four HMMs were constructed based on the
      cohort of non-demented young, middle-aged, elder and demented elder subjects
      separately. Classification was carried out using a data set including both non
      demented and demented individuals with a wide age range. RESULTS: The proposed
      HMMs have succeeded in recognition of individual who has mild Alzheimer's disease
      and achieved a better classification accuracy compared to other related works
      using different classifiers. Results have shown the ability of the proposed
      modeling for recognition of early dementia. CONCLUSION: The findings from this
      research will allow individual classification to support the early diagnosis and
      prediction of dementia. By using the brain MRI-based HMMs developed in our
      proposed research, it will be more efficient, robust and can be easily used by
      clinicians as a computer-aid tool for validating imaging bio-markers for early
      prediction of dementia.

PMID- 24564962
TI  - Highly precise protein-protein interaction prediction based on consensus between
      template-based and de novo docking methods.
AB  - BACKGROUND: Elucidation of protein-protein interaction (PPI) networks is
      important for understanding disease mechanisms and for drug discovery. Tertiary
      structure-based in silico PPI prediction methods have been developed with two
      typical approaches: a method based on template matching with known protein
      structures and a method based on de novo protein docking. However, the template
      based method has a narrow applicable range because of its use of template
      information, and the de novo docking based method does not have good prediction
      performance. In addition, both of these in silico prediction methods have
      insufficient precision, and require validation of the predicted PPIs by
      biological experiments, leading to considerable expenditure; therefore, PPI
      prediction methods with greater precision are needed. RESULTS: We have proposed a
      new structure-based PPI prediction method by combining template-based prediction
      and de novo docking prediction. When we applied the method to the human apoptosis
      signaling pathway, we obtained a precision value of 0.333, which is higher than
      that achieved using conventional methods (0.231 for PRISM, a template-based
      method, and 0.145 for MEGADOCK, a non-template-based method), while maintaining
      an F-measure value (0.285) comparable to that obtained using conventional methods
      (0.296 for PRISM, and 0.220 for MEGADOCK). CONCLUSIONS: Our consensus method
      successfully predicted a PPI network with greater precision than conventional
      template/non-template methods, which may thus reduce the cost of validation by
      laboratory experiments for confirming novel PPIs from predicted PPIs. Therefore,
      our method may serve as an aid for promoting interactome analysis.

PMID- 24564963
TI  - Promyelocytic leukemia zinc-finger induction signs mesenchymal stem cell
      commitment: identification of a key marker for stemness maintenance?
AB  - INTRODUCTION: Mesenchymal stem cells (MSCs) are an attractive cell source for
      cartilage and bone tissue engineering given their ability to differentiate into
      chondrocytes and osteoblasts. However, the common origin of these two specialized
      cell types raised the question about the identification of regulatory pathways
      determining the differentiation fate of MSCs into chondrocyte or osteoblast.
      METHODS: Chondrogenesis, osteoblastogenesis, and adipogenesis of human and mouse
      MSC were induced by using specific inductive culture conditions. Expression of
      promyelocytic leukemia zinc-finger (PLZF) or differentiation markers in MSCs was
      determined by RT-qPCR. PLZF-expressing MSC were implanted in a mouse
      osteochondral defect model and the neotissue was analyzed by routine histology
      and microcomputed tomography. RESULTS: We found out that PLZF is not expressed in
      MSCs and its expression at early stages of MSC differentiation is the mark of
      their commitment toward the three main lineages. PLZF acts as an upstream
      regulator of both Sox9 and Runx2, and its overexpression in MSC enhances
      chondrogenesis and osteogenesis while it inhibits adipogenesis. In vivo,
      implantation of PLZF-expressing MSC in mice with full-thickness osteochondral
      defects resulted in the formation of a reparative tissue resembling cartilage and
      bone. CONCLUSIONS: Our findings demonstrate that absence of PLZF is required for
      stemness maintenance and its expression is an early event at the onset of MSC
      commitment during the differentiation processes of the three main lineages.

PMID- 24564964
TI  - Modeling protein conformational transitions by a combination of coarse-grained
      normal mode analysis and robotics-inspired methods.
AB  - BACKGROUND: Obtaining atomic-scale information about large-amplitude
      conformational transitions in proteins is a challenging problem for both
      experimental and computational methods. Such information is, however, important
      for understanding the mechanisms of interaction of many proteins. METHODS: This
      paper presents a computationally efficient approach, combining methods
      originating from robotics and computational biophysics, to model protein
      conformational transitions. The ability of normal mode analysis to predict
      directions of collective, large-amplitude motions is applied to bias the
      conformational exploration performed by a motion planning algorithm. To reduce
      the dimension of the problem, normal modes are computed for a coarse-grained
      elastic network model built on short fragments of three residues. Nevertheless,
      the validity of intermediate conformations is checked using the all-atom model,
      which is accurately reconstructed from the coarse-grained one using closed-form
      inverse kinematics. RESULTS: Tests on a set of ten proteins demonstrate the
      ability of the method to model conformational transitions of proteins within a
      few hours of computing time on a single processor. These results also show that
      the computing time scales linearly with the protein size, independently of the
      protein topology. Further experiments on adenylate kinase show that main features
      of the transition between the open and closed conformations of this protein are
      well captured in the computed path. CONCLUSIONS: The proposed method enables the
      simulation of large-amplitude conformational transitions in proteins using very
      few computational resources. The resulting paths are a first approximation that
      can directly provide important information on the molecular mechanisms involved
      in the conformational transition. This approximation can be subsequently refined
      and analyzed using state-of-the-art energy models and molecular modeling methods.

PMID- 24564965
TI  - Modeling inflammation and oxidative stress in gastrointestinal disease
      development using novel organotypic culture systems.
AB  - Gastroesophageal reflux disease (GERD), Barrett's esophagus (BE), graft-versus
      host disease (GVHD), and inflammatory bowel diseases such as ulcerative colitis
      and Crohn's disease are common human gastrointestinal diseases that share
      inflammation as a key driver for their development. A general outcome resulting
      from these chronic inflammatory conditions is increased oxidative stress.
      Oxidative stress is caused by the generation of reactive oxygen and nitrogen
      species that are part of the normal inflammatory response, but are also capable
      of damaging cellular DNA, protein, and organelles. Damage to DNA can include DNA
      strand breaks, point mutations due to DNA adducts, as well as alterations in
      methylation patterns leading to activation of oncogenes or inactivation of tumor
      suppressors. There are a number of significant long-term consequences associated
      with chronic oxidative stress, most notably cancer. Infiltrating immune cells and
      stromal components of tissue including fibroblasts contribute to dynamic changes
      occurring in tissue related to disease development. Immune cells can potentiate
      oxidative stress, and fibroblasts have the capacity to contribute to advanced
      growth and proliferation of the epithelium and any resultant cancers. Disease
      models for GERD, BE, GVHD, and ulcerative colitis based on three-dimensional
      human cell and tissue culture systems that recapitulate in vivo growth and
      differentiation in inflammatory-associated microphysiological environments would
      enhance our understanding of disease progression and improve our ability to test
      for disease-prevention strategies. The development of physiologically relevant,
      human cell-based culture systems is therefore a major focus of our research.
      These novel models will be of enormous value, allowing us to test hypotheses and
      advance our understanding of these disorders, and will have a translational
      impact allowing us to more rapidly develop therapeutic and chemopreventive
      agents. In summary, this work to develop advanced human cell-based models of
      inflammatory conditions will greatly improve our ability to study, prevent, and
      treat GERD, BE, GVHD, and inflammatory bowel disease. The work will also foster
      the development of novel therapeutic and preventive strategies that will improve
      patient care for these important clinical conditions. 

PMID- 24564966
TI  - Prediction of protein-RNA residue-base contacts using two-dimensional conditional
      random field with the lasso.
AB  - BACKGROUND: To uncover molecular functions and networks in biological cellular
      systems, it is important to dissect interactions between proteins and RNAs. Many
      studies have been performed to investigate and analyze interactions between
      protein amino acid residues and RNA bases. In terms of interactions between
      residues in proteins, it is generally accepted that an amino acid residue at
      interacting sites has coevolved together with the partner residue in order to
      keep the interaction between residues in proteins. Based on this hypothesis, in
      our previous study to identify residue-residue contact pairs in interacting
      proteins, we made calculations of mutual information (M I) between amino acid
      residues from some multiple sequence alignment of homologous proteins, and
      combined it with a discriminative random field (DRF) approach, which is a special
      type of conditional random fields (CRFs) and has been proved useful for the
      purpose of extracting distinguishing areas from a photograph in the image
      processing field. Recently, the evolutionary correlation of interactions between
      residues and DNA bases has also been found in certain transcription factors and
      the DNA-binding sites. RESULTS: In this paper, we employ more generic two
      dimensional CRFs than such DRFs to predict interactions between protein amino
      acid residues and RNA bases. In addition, we introduce labels representing kinds
      of amino acids and bases as local features of a CRF. Furthermore, we examine the
      utility of L1-norm regularization (lasso) for the CRF. For evaluation of our
      method, we use residue-base interactions between several Pfam domains and Rfam
      entries, conduct cross-validation, and calculate the average AUC (Area under ROC
      Curve) score. The results suggest that our CRF-based method using mutual
      information and labels with the lasso is useful for further improving the
      performance, especially provided that the features of CRF are successfully
      reduced by the lasso approach. CONCLUSIONS: We propose simple and generic two
      dimensional CRF models using labels and mutual information with the lasso. Use of
      the CRF-based method in combination with the lasso is particularly useful for
      predicting the residue-base contacts in protein-RNA interactions.

PMID- 24564967
TI  - Mimivirus circulation among wild and domestic mammals, Amazon Region, Brazil.
AB  - To investigate circulation of mimiviruses in the Amazon Region of Brazil, we
      surveyed 513 serum samples from domestic and wild mammals. Neutralizing
      antibodies were detected in 15 sample pools, and mimivirus DNA was detected in 9
      pools of serum from capuchin monkeys and in 16 pools of serum from cattle. 

PMID- 24564969
TI  - X-ray energy-dispersive spectrometry during in situ liquid cell studies using an
      analytical electron microscope.
AB  - The use of analytical spectroscopies during scanning/transmission electron
      microscope (S/TEM) investigations of micro- and nano-scale structures has become
      a routine technique in the arsenal of tools available to today's materials
      researchers. Essential to implementation and successful application of
      spectroscopy to characterization is the integration of numerous technologies,
      which include electron optics, specimen holders, and associated detectors. While
      this combination has been achieved in many instrument configurations, the
      integration of X-ray energy-dispersive spectroscopy and in situ liquid
      environmental cells in the S/TEM has to date been elusive. In this work we
      present the successful incorporation/modifications to a system that achieves this
      functionality for analytical electron microscopy. 

PMID- 24564968
TI  - Global medicine: is it ethical or morally justifiable for doctors and other
      healthcare workers to go on strike?
AB  - BACKGROUND: Doctor and healthcare worker (HCW) strikes are a global phenomenon
      with the potential to negatively impact on the quality of healthcare services and
      the doctor-patient relationship. Strikes are a legitimate deadlock breaking
      mechanism employed when labour negotiations have reached an impasse during
      collective bargaining. Striking doctors usually have a moral dilemma between
      adherence to the Hippocratic tenets of the medical profession and fiduciary
      obligation to patients. In such circumstances the ethical principles of respect
      for autonomy, justice and beneficence all come into conflict, whereby doctors
      struggle with their role as ordinary employees who are rightfully entitled to a
      just wage for just work versus their moral obligations to patients and society.
      DISCUSSION: It has been argued that to deny any group of workers, including
      "essential workers" the right to strike is akin to enslavement which is ethically
      and morally indefensible. While HCW strikes occur globally, the impact appears
      more severe in developing countries challenged by poorer socio-economic
      circumstances, embedded infrastructural deficiencies, and lack of viable
      alternative means of obtaining healthcare. These communities appear to satisfy
      the criteria for vulnerability and may be deserving of special ethical
      consideration when doctor and HCW strikes are contemplated. SUMMARY: The right to
      strike is considered a fundamental right whose derogation would be inimical to
      the proper functioning of employer/employee collective bargaining in democratic
      societies. Motivations for HCW strikes include the natural pressure to fulfil
      human needs and the paradigm shift in modern medical practice, from self
      employment and benevolent paternalism, to managed healthcare and consumer rights.
      Minimizing the incidence and impact of HCW strikes will require an ethical
      approach from all stakeholders, and recognition that all parties have an equal
      moral obligation to serve the best interests of society. Employers should
      implement legitimate collective bargaining agreements in a timely manner and high
      handed actions such as mass-firing of striking HCWs, or unjustifiable
      disciplinary action by regulators should be avoided. Minimum service level
      agreements should be implemented to mitigate the impact of HCW strikes on
      indigent populations. Striking employees including HCWs should also desist from
      making unrealistic wage demands which could bankrupt governments/employers or
      hamper provision of other equally important social services to the general
      population.

PMID- 24564970
TI  - Rapid sampling of local minima in protein energy surface and effective reduction
      through a multi-objective filter.
AB  - BACKGROUND: Many problems in protein modeling require obtaining a discrete
      representation of the protein conformational space as an ensemble of
      conformations. In ab-initio structure prediction, in particular, where the goal
      is to predict the native structure of a protein chain given its amino-acid
      sequence, the ensemble needs to satisfy energetic constraints. Given the
      thermodynamic hypothesis, an effective ensemble contains low-energy conformations
      which are similar to the native structure. The high-dimensionality of the
      conformational space and the ruggedness of the underlying energy surface
      currently make it very difficult to obtain such an ensemble. Recent studies have
      proposed that Basin Hopping is a promising probabilistic search framework to
      obtain a discrete representation of the protein energy surface in terms of local
      minima. Basin Hopping performs a series of structural perturbations followed by
      energy minimizations with the goal of hopping between nearby energy minima. This
      approach has been shown to be effective in obtaining conformations near the
      native structure for small systems. Recent work by us has extended this framework
      to larger systems through employment of the molecular fragment replacement
      technique, resulting in rapid sampling of large ensembles. METHODS: This paper
      investigates the algorithmic components in Basin Hopping to both understand and
      control their effect on the sampling of near-native minima. Realizing that such
      an ensemble is reduced before further refinement in full ab-initio protocols, we
      take an additional step and analyze the quality of the ensemble retained by
      ensemble reduction techniques. We propose a novel multi-objective technique based
      on the Pareto front to filter the ensemble of sampled local minima. RESULTS AND
      CONCLUSIONS: We show that controlling the magnitude of the perturbation allows
      directly controlling the distance between consecutively-sampled local minima and,
      in turn, steering the exploration towards conformations near the native
      structure. For the minimization step, we show that the addition of Metropolis
      Monte Carlo-based minimization is no more effective than a simple greedy search.
      Finally, we show that the size of the ensemble of sampled local minima can be
      effectively and efficiently reduced by a multi-objective filter to obtain a
      simpler representation of the probed energy surface.

PMID- 24564971
TI  - Is the relationship between the built environment and physical activity moderated
      by perceptions of crime and safety?
AB  - BACKGROUND: Direct relationships between safety concerns and physical activity
      have been inconsistently patterned in the literature. To tease out these
      relationships, crime, pedestrian, and traffic safety were examined as moderators
      of built environment associations with physical activity. METHODS: Exploratory
      analyses used two cross-sectional studies of 2068 adults ages 20-65 and 718
      seniors ages 66+ with similar designs and measures. The studies were conducted in
      the Baltimore, Maryland-Washington, DC and Seattle-King County, Washington
      regions during 2001-2005 (adults) and 2005-2008 (seniors). Participants were
      recruited from areas selected to sample high- and low- income and walkability.
      Independent variables perceived crime, traffic, and pedestrian safety were
      measured using scales from validated instruments. A GIS-based walkability index
      was calculated for a street-network buffer around each participant's home
      address. Outcomes were total physical activity measured using accelerometers and
      transportation and leisure walking measured with validated self-reports (IPAQ
      long). Mixed effects regression models were conducted separately for each sample.
      RESULTS: Of 36 interactions evaluated across both studies, only 5 were
      significant (p< .05). Significant interactions did not consistently support a
      pattern of highest physical activity when safety was rated high and environments
      were favorable. There was not consistent evidence that safety concerns reduced
      the beneficial effects of favorable environments on physical activity. Only
      pedestrian safety showed evidence of a consistent main effect with physical
      activity outcomes, possibly because pedestrian safety items (e.g., crosswalks,
      sidewalks) were not as subjective as those on the crime and traffic safety
      scales. CONCLUSIONS: Clear relationships between crime, pedestrian, and traffic
      safety with physical activity levels remain elusive. The development of more
      precise safety variables and the use of neighborhood-specific physical activity
      outcomes may help to elucidate these relationships.

PMID- 24564972
TI  - iSVP: an integrated structural variant calling pipeline from high-throughput
      sequencing data.
AB  - BACKGROUND: Structural variations (SVs), such as insertions, deletions,
      inversions, and duplications, are a common feature in human genomes, and a number
      of studies have reported that such SVs are associated with human diseases.
      Although the progress of next generation sequencing (NGS) technologies has led to
      the discovery of a large number of SVs, accurate and genome-wide detection of SVs
      remains challenging. Thus far, various calling algorithms based on NGS data have
      been proposed. However, their strategies are diverse and there is no tool able to
      detect a full range of SVs accurately. RESULTS: We focused on evaluating the
      performance of existing deletion calling algorithms for various spanning ranges
      from low- to high-coverage simulation data. The simulation data was generated
      from a whole genome sequence with artificial SVs constructed based on the
      distribution of variants obtained from the 1000 Genomes Project. From the
      simulation analysis, deletion calls of various deletion sizes were obtained with
      each caller, and it was found that the performance was quite different according
      to the type of algorithms and targeting deletion size. Based on these results, we
      propose an integrated structural variant calling pipeline (iSVP) that combines
      existing methods with a newly devised filtering and merging processes. It
      achieved highly accurate deletion calling with >90% precision and >90% recall on
      the 30* read data for a broad range of size. We applied iSVP to the whole-genome
      sequence data of a CEU HapMap sample, and detected a large number of deletions,
      including notable peaks around 300 bp and 6,000 bp, which corresponded to Alus
      and long interspersed nuclear elements, respectively. In addition, many of the
      predicted deletions were highly consistent with experimentally validated ones by
      other studies. CONCLUSIONS: We present iSVP, a new deletion calling pipeline to
      obtain a genome-wide landscape of deletions in a highly accurate manner. From
      simulation and real data analysis, we show that iSVP is broadly applicable to
      human whole-genome sequencing data, which will elucidate relationships between
      SVs across genomes and associated diseases or biological functions.

PMID- 24564973
TI  - Mass type-specific sparse representation for mass classification in computer
      aided detection on mammograms.
AB  - BACKGROUND: Breast cancer is the leading cause of both incidence and mortality in
      women population. For this reason, much research effort has been devoted to
      develop Computer-Aided Detection (CAD) systems for early detection of the breast
      cancers on mammograms. In this paper, we propose a new and novel dictionary
      configuration underpinning sparse representation based classification (SRC). The
      key idea of the proposed algorithm is to improve the sparsity in terms of mass
      margins for the purpose of improving classification performance in CAD systems.
      METHODS: The aim of the proposed SRC framework is to construct separate
      dictionaries according to the types of mass margins. The underlying idea behind
      our method is that the separated dictionaries can enhance the sparsity of mass
      class (true-positive), leading to an improved performance for differentiating
      mammographic masses from normal tissues (false-positive). When a mass sample is
      given for classification, the sparse solutions based on corresponding
      dictionaries are separately solved and combined at score level. Experiments have
      been performed on both database (DB) named as Digital Database for Screening
      Mammography (DDSM) and clinical Full Field Digital Mammogram (FFDM) DBs. In our
      experiments, sparsity concentration in the true class (SCTC) and area under the
      Receiver operating characteristic (ROC) curve (AUC) were measured for the
      comparison between the proposed method and a conventional single dictionary based
      approach. In addition, a support vector machine (SVM) was used for comparing our
      method with state-of-the-arts classifier extensively used for mass
      classification. RESULTS: Comparing with the conventional single dictionary
      configuration, the proposed approach is able to improve SCTC of up to 13.9% and
      23.6% on DDSM and FFDM DBs, respectively. Moreover, the proposed method is able
      to improve AUC with 8.2% and 22.1% on DDSM and FFDM DBs, respectively. Comparing
      to SVM classifier, the proposed method improves AUC with 2.9% and 11.6% on DDSM
      and FFDM DBs, respectively. CONCLUSIONS: The proposed dictionary configuration is
      found to well improve the sparsity of dictionaries, resulting in an enhanced
      classification performance. Moreover, the results show that the proposed method
      is better than conventional SVM classifier for classifying breast masses subject
      to various margins from normal tissues.

PMID- 24564974
TI  - Diabetes in Algeria and challenges for health policy: a literature review of
      prevalence, cost, management and outcomes of diabetes and its complications.
AB  - BACKGROUND: Diabetes has become an increasingly prevalent and severe public
      health issue in Algeria. This article investigates the prevalence, the cost and
      the management of this disease. Its first objective is to better understand the
      burden (both from an epidemiological and economic perspective) and management of
      diabetes. The second objective is to understand the health policy strategy
      adopted by Algeria in order to respond to the disease. METHODS: We conducted a
      literature review of prevalence, costs, management and outcomes of diabetes and
      its complications. This was complemented by data compilations and results of
      expert consultations. RESULTS: The epidemiology of diabetes is continually
      evolving and is becoming more problematic. The national evidence suggests that
      the prevalence of diabetes in Algeria has increased from 6.8% in 1990 to 12.29%
      in 2005, but is quite higher among certain groups and areas of the country. This
      disease affects all population groups, especially 35-70 year olds, who constitute
      a large segment of the working population. There are very few estimates of the
      cost of diabetes. These include a 1998 study on the total cost of type 1 diabetes
      (USD 11.6 million, which, inflated to 2013 value, totals to USD 16.6 million), a
      study on the cost of complications in 2010 (at 2013 value, ranging from USD 141
      for first-year treatment of peripheral vascular disease to USD 30,441 for first
      year cost of renal transplantation) and the 2013 IDF estimates of total cost of
      type 1 and type 2 diabetes (USD 513 million). CONCLUSIONS: As the prevalence of
      diabetes continues to increase, the financial burden will increasingly weigh
      heavily on social security resources and the government budget. Future priorities
      must focus on empowering general practitioners in treating type 2 diabetes,
      improving screening of diabetes and its complications, tackling the growing
      obesity epidemic, strengthening health information systems and implementing the
      national diabetes prevention and control plan.

PMID- 24564975
TI  - A novel approach to minimize false discovery rate in genome-wide data analysis.
AB  - BACKGROUND: High-throughput technologies, such as DNA microarray, have
      significantly advanced biological and biomedical research by enabling researchers
      to carry out genome-wide screens. One critical task in analyzing genome-wide
      datasets is to control the false discovery rate (FDR) so that the proportion of
      false positive features among those called significant is restrained. Recently a
      number of FDR control methods have been proposed and widely practiced, such as
      the Benjamini-Hochberg approach, the Storey approach and Significant Analysis of
      Microarrays (SAM). METHODS: This paper presents a straight-forward yet powerful
      FDR control method termed miFDR, which aims to minimize FDR when calling a fixed
      number of significant features. We theoretically proved that the strategy used by
      miFDR is able to find the optimal number of significant features when the desired
      FDR is fixed. RESULTS: We compared miFDR with the BH approach, the Storey
      approach and SAM on both simulated datasets and public DNA microarray datasets.
      The results demonstrated that miFDR outperforms others by identifying more
      significant features under the same FDR cut-offs. Literature search showed that
      many genes called only by miFDR are indeed relevant to the underlying biology of
      interest. CONCLUSIONS: FDR has been widely applied to analyzing high-throughput
      datasets allowed for rapid discoveries. Under the same FDR threshold, miFDR is
      capable to identify more significant features than its competitors at a
      compatible level of complexity. Therefore, it can potentially generate great
      impacts on biological and biomedical research. AVAILABILITY: If interested,
      please contact the authors for getting miFDR.

PMID- 24564977
TI  - Adaptive bandwidth kernel density estimation for next-generation sequencing data.
AB  - BACKGROUND: High-throughput sequencing experiments can be viewed as measuring
      some sort of a "genomic signal" that may represent a biological event such as the
      binding of a transcription factor to the genome, locations of chromatin
      modifications, or even a background or control condition. Numerous algorithms
      have been developed to extract different kinds of information from such data.
      However, there has been very little focus on the reconstruction of the genomic
      signal itself. Such reconstructions may be useful for a variety of purposes
      ranging from simple visualization of the signals to sophisticated comparison of
      different datasets. METHODS: Here, we propose that adaptive-bandwidth kernel
      density estimators are well-suited for genomic signal reconstructions. This class
      of estimators is a natural extension of the fixed-bandwidth estimators that have
      been employed in several existing ChIP-Seq analysis programs. RESULTS: Using a
      set of ChIP-Seq datasets from the ENCODE project, we show that adaptive-bandwidth
      estimators have greater accuracy at signal reconstruction compared to fixed
      bandwidth estimators, and that they have significant advantages in terms of
      visualization as well. For both fixed and adaptive-bandwidth schemes, we
      demonstrate that smoothing parameters can be set automatically using a held-out
      set of tuning data. We also carry out a computational complexity analysis of the
      different schemes and confirm through experimentation that the necessary
      computations can be readily carried out on a modern workstation without any
      significant issues.

PMID- 24564976
TI  - Computational drug repositioning through heterogeneous network clustering.
AB  - BACKGROUND: Given the costly and time consuming process and high attrition rates
      in drug discovery and development, drug repositioning or drug repurposing is
      considered as a viable strategy both to replenish the drying out drug pipelines
      and to surmount the innovation gap. Although there is a growing recognition that
      mechanistic relationships from molecular to systems level should be integrated
      into drug discovery paradigms, relatively few studies have integrated information
      about heterogeneous networks into computational drug-repositioning candidate
      discovery platforms. RESULTS: Using known disease-gene and drug-target
      relationships from the KEGG database, we built a weighted disease and drug
      heterogeneous network. The nodes represent drugs or diseases while the edges
      represent shared gene, biological process, pathway, phenotype or a combination of
      these features. We clustered this weighted network to identify modules and then
      assembled all possible drug-disease pairs (putative drug repositioning
      candidates) from these modules. We validated our predictions by testing their
      robustness and evaluated them by their overlap with drug indications that were
      either reported in published literature or investigated in clinical trials.
      CONCLUSIONS: Previous computational approaches for drug repositioning focused
      either on drug-drug and disease-disease similarity approaches whereas we have
      taken a more holistic approach by considering drug-disease relationships also.
      Further, we considered not only gene but also other features to build the disease
      drug networks. Despite the relative simplicity of our approach, based on the
      robustness analyses and the overlap of some of our predictions with drug
      indications that are under investigation, we believe our approach could
      complement the current computational approaches for drug repositioning candidate
      discovery.

PMID- 24564978
TI  - Cloning and characterization of chitinases from interior spruce and lodgepole
      pine.
AB  - Chitinases have been implicated in the defence of conifers against insects and
      pathogens. cDNA for six chitinases were cloned from interior spruce (Picea glauca
      x engelmannii) and four from lodgepole pine (Pinus contorta). The cloned interior
      spruce chitinases were annotated class I PgeChia1-1 and PgeChia1-2, class II
      PgeChia2-1, class IV PgeChia4-1, and class VII PgeChia7-1 and PgeChia7-2;
      lodgepole pine chitinases were annotated class I PcChia1-1, class IV PcChia4-1,
      and class VII PcChia7-1 and PcChia7-2. Chitinases were expressed in Escherichia
      coli with maltose-binding-protein tags and soluble proteins purified. Functional
      characterization demonstrated chitinolytic activity for the three class I
      chitinases PgeChia1-1, PgeChia1-2 and PcChia1-1. Transcript analysis established
      strong induction of most of the tested chitinases, including all three class I
      chitinases, in interior spruce and lodgepole pine in response to inoculation with
      bark beetle associated fungi (Leptographium abietinum and Grosmannia clavigera)
      and in interior spruce in response to weevil (Pissodes strobi) feeding. Evidence
      of chitinolytic activity and inducibility by fungal and insect attack support the
      involvement of these chitinases in conifer defense. 

PMID- 24564979
TI  - Mapping of the complement C9 binding domain on Trichinella spiralis paramyosin.
AB  - BACKGROUND: Trichinellosis is an important foodborne zoonosis that is distributed
      worldwide. Trichinella spiralis may evade host complement-mediated attack by
      expressing complement inhibitory proteins, such as paramyosin (Pmy). Previous
      studies have shown that Trichinella spiralis paramyosin (Ts-Pmy) is able to bind
      to the human complement component C9 to inhibit the complement activation and
      protect the parasite from complement-mediated attack. Further determination of
      the complement-binding domain on Ts-pmy will enable us to better understand the
      Ts-Pmy's biofunction in the immune evasion and provide feasible approach to
      develop epitope-based subunit vaccine against trichinellosis. METHODS: The
      complement C9 binding region on Ts-Pmy was determined by expression of overlapped
      fragments of Ts-Pmy and their binding activities to C9. The exact binding site
      was further narrowed-down to a 14-amino acid peptide at C-terminus using
      synthesized peptides with different size of amino acid sequence. The C9
      complement-binding of the 14-amino acid peptide and its interference in the C9
      polymerization and the complement-mediated lysis of rabbit erythrocytes was
      investigated. RESULTS: The protein interaction between human C9 and native Ts-Pmy
      was further confirmed by immunoprecipitation with T. spiralis lysates. The
      fragmental expression and C9 binding assays identified that the binding region of
      Ts-Pmy to C9 is located within 831-885 of Ts-Pmy C-terminus. The exact binding
      site on Ts-Pmy to C9 was narrowed down to 14 amino acid residues (866Val-879Met)
      by using different sizes of synthesized peptides. In the presence of the
      synthesized 14-amino acid peptide, human C9 polymerization and the hemolytic
      activity of the human complement was inhibited. CONCLUSIONS: Our results revealed
      the precise molecular basis for T. spiralis to produce Ts-Pmy as an
      immunomodulator to evade the attack of the host complement system as a survival
      mechanism.

PMID- 24564980
TI  - SAVI: a statistical algorithm for variant frequency identification.
AB  - BACKGROUND: Many problems in biomedical research can be posed as a comparison
      between related samples (healthy vs. disease, subtypes of the same disease,
      longitudinal data representing the progression of a disease, etc). In the cases
      in which the distinction has a genetic or epigenetic basis, next-generation
      sequencing technologies have become a major tool for obtaining the difference
      between the samples. A commonly occurring application is the identification of
      somatic mutations occurring in tumor tissue samples driving a single cell to
      expand clonally. In this case, the progression of the disease can be traced
      through the trajectory of the frequency of the oncogenic alleles. Thus obtaining
      precise estimates of the frequency of abnormal alleles at various stages of the
      disease is paramount to understanding the processes driving it. Although the
      procedure is conceptually simple, technical difficulties arise due to
      inhomogeneous samples, existence of competing subclonal populations, and
      systematic and non-systematic errors introduced by the sequencing technologies.
      RESULTS: We present a method, Statistical Algorithm for Variant Frequency
      Identification (SAVI), to estimate the frequency of alleles in a set of samples.
      The method employs Bayesian analysis and uses an iterative procedure to derive
      empirical priors. The approach allows for the comparison of allele frequencies
      across several samples, e.g. normal/tumor pairs and more complex experimental
      designs comparing multiple samples in tumor progression, as well as analyzing
      sequencing data from RNA sequencing experiments. CONCLUSIONS: Analyzing
      sequencing data through estimating allele frequencies using empirical Bayes
      methods is a powerful complement to the ever-increasing throughput of the
      sequencing technologies.

PMID- 24564981
TI  - The association of antiphospholipid antibodies with cardiopulmonary
      manifestations of systemic sclerosis.
AB  - OBJECTIVES: To determine the prevalence and correlates of antiphospholipid
      antibodies (APLA) in systemic sclerosis (SSc). METHODS: Nine hundred and forty
      SSc patients were tested for APLA using an ELISA assay at recruitment. Clinical
      manifestations were defined as present, if ever present from SSc diagnosis.
      Logistic regression analysis was used to determine the associations of APLA.
      RESULTS: One or more types of APLA were present in 226 (24.0%) patients.
      Anticardiolipin (ACA) IgG (ACA-IgG) antibodies were associated with right heart
      catheter-diagnosed pulmonary arterial hypertension (PAH), with higher titres
      corresponding with a higher likelihood of PAH (moderate titre (20-39 U/ml) ACA
      IgG odds ratio [OR] 1.70, 95% CI: 1.01-2.93, p=0.047; high titre (>40 U/ml) ACA
      IgG OR 4.60, 95% CI:1.02-20.8, p=0.047). Both ACA-IgM (OR 2.04, 95% CI: 1.4-3.0,
      p<0.0001) and ACA-IgG (OR 1.84, 95% CI: 1.2-2.8, p=0.005) were associated with
      interstitial lung disease (ILD). Increasing ACA-IgM and IgG titres were
      associated with increased likelihood of ILD. ACA-IgG was a marker of coexistent
      pulmonary hypertension and ILD (ILD-PH) (OR 2.10, 95% CI: 1.1-4.2, p=0.036). We
      also found an association between ACA-IgG and digital ulcers (OR 1.76, 95% CI:
      1.16-2.67, p=0.008) and ACA-IgM and Raynaud's phenomenon (OR 2.39, 95% CI: 1.08
      5.27, p=0.031). There was no association between APLA and SSc disease subtype,
      peak skin score, presence of other autoantibodies, mortality or other disease
      manifestations. CONCLUSIONS: The association of APLA with PAH, ILD, ILD-PH,
      Raynaud's phenomenon and digital ulcers suggests that endothelial abnormalities
      and small vessel thrombosis may be important in the pathogenesis of these disease
      features.

PMID- 24564982
TI  - Stigmatization of people living with HIV/AIDS by healthcare workers at a tertiary
      hospital in KwaZulu-Natal, South Africa: a cross-sectional descriptive study.
AB  - BACKGROUND: The issue of stigma is very important in the battle against HIV/AIDS
      in Africa since it may affect patient attendance at healthcare centres for
      obtaining antiretroviral (ARV) medications and regular medical check-ups.
      Stigmatization creates an unnecessary culture of secrecy and silence based on
      ignorance and fear of victimization. This study was designed to determine if
      there is external stigmatization of people living with HIV and AIDS (PLWHA) by
      health care workers (HCWs) at a tertiary hospital in KwaZulu-Natal (KZN)
      province, South Africa. The study investigated the impact of knowledge of
      HIV/AIDS by HCWs on treatment of patients, as well as the comfort level and
      attitude of HCWs when rendering care to PLWHA. METHODS: A descriptive cross
      sectional study was designed to collect data using an anonymous self-administered
      structured questionnaire from 334 HCWs. The study was conducted in clinical
      departments of a large multidisciplinary 922-bed tertiary care teaching hospital
      in Durban, KZN. RESULTS: Overall HCWs had an above average knowledge about
      HIV/AIDS although some gaps in knowledge were identified. Tests of statistical
      significance showed that there was association between level of education and
      knowledge of HIV/AIDs (p <= 0.001); occupation and knowledge of HIV/AIDS (p <=
      0.001); and gender and knowledge of HIV/AIDS (p = 0.004). Test for comfort level
      was only significant for gender, with males showing more comfort and empathy when
      dealing with PLWHA (p = 0.003). The study also revealed that patients were
      sometimes tested for HIV without informed consent before surgery, due to fear of
      being infected, and there was some gossiping about patients' HIV status by HCWs,
      thereby compromising patient confidentiality. The majority of HCWs showed a
      willingness to report incidents of stigmatization and discrimination to higher
      authorities, for better monitoring and control. CONCLUSIONS: Although knowledge,
      attitude and comfort level of HCWs taking care of PLWHA was above average,
      enforcement of existing antidiscrimination laws and continuing education in
      medical ethics and healthcare law, would greatly improve the performance of HCWs
      taking care of PLWHAs. More psychological support and counselling should be
      provided to HCWs, to further reduce the impact of stigmatization and
      discrimination against PLWHA.

PMID- 24564984
TI  - Reducing the cesarean delivery rates for breech presentations: administration of
      spinal anesthesia facilitates manipulation to cephalic presentation, but is it
      cost saving?
AB  - BACKGROUND: External cephalic version (ECV) is infrequently performed and 98% of
      breech presenting fetuses are delivered surgically. Neuraxial analgesia can
      increase the success rate of ECV significantly, potentially reducing cesarean
      delivery rates for breech presentation. The current study aims to determine
      whether the additional cost to the hospital of spinal anesthesia for ECV is
      offset by cost savings generated by reduced cesarean delivery. METHODS: In our
      tertiary hospital, three variables manpower, disposables, and fixed costs were
      calculated for ECV, ECV plus anesthetic doses of spinal block, vaginal delivery
      and cesarean delivery. Total procedure costs were compared for possible delivery
      pathways. Manpower data were obtained from management payroll, fixed costs by
      calculating cost/lifetime usage rate and disposables were micro-costed in 2008,
      expressed in 2013 NIS. RESULTS: Cesarean delivery is the most expensive option,
      11670.54 NIS and vaginal delivery following successful ECV under spinal block
      costs 5497.2 NIS. ECV alone costs 960.21 NIS, ECV plus spinal anesthesia costs
      1386.97 NIS. The highest individual cost items for vaginal, cesarean delivery and
      ECV were for manpower. Expensive fixed costs for cesarean delivery included
      operating room trays and postnatal hospitalization (minimum 3 days). ECV with
      spinal block is cheaper due to lower expected cesarean delivery rate and its
      lower associated costs. CONCLUSIONS: The additional cost of the spinal anesthesia
      is offset by increased success rates for the ECV procedure resulting in reduction
      in the cesarean delivery rate.

PMID- 24564985
TI  - Gaussian process regression model for normalization of LC-MS data using scan
      level information.
AB  - BACKGROUND: Differences in sample collection, biomolecule extraction, and
      instrument variability introduce bias to data generated by liquid chromatography
      coupled with mass spectrometry (LC-MS). Normalization is used to address these
      issues. In this paper, we introduce a new normalization method using the Gaussian
      process regression model (GPRM) that utilizes information from individual scans
      within an extracted ion chromatogram (EIC) of a peak. The proposed method is
      particularly applicable for normalization based on analysis order of LC-MS runs.
      Our method uses measurement variabilities estimated through LC-MS data acquired
      from quality control samples to correct for bias caused by instrument drift.
      Maximum likelihood approach is used to find the optimal parameters for the fitted
      GPRM. We review several normalization methods and compare their performance with
      GPRM. RESULTS: To evaluate the performance of different normalization methods, we
      consider LC-MS data from a study where metabolomic approach is utilized to
      discover biomarkers for liver cancer. The LC-MS data were acquired by analysis of
      sera from liver cancer patients and cirrhotic controls. In addition, LC-MS runs
      from a quality control (QC) sample are included to assess the run to run
      variability and to evaluate the ability of various normalization method in
      reducing this undesired variability. Also, ANOVA models are applied to the
      normalized LC-MS data to identify ions with intensity measurements that are
      significantly different between cases and controls. CONCLUSIONS: One of the
      challenges in using label-free LC-MS for quantitation of biomolecules is
      systematic bias in measurements. Several normalization methods have been
      introduced to overcome this issue, but there is no universally applicable
      approach at the present time. Each data set should be carefully examined to
      determine the most appropriate normalization method. We review here several
      existing methods and introduce the GPRM for normalization of LC-MS data. Through
      our in-house data set, we show that the GPRM outperforms other normalization
      methods considered here, in terms of decreasing the variability of ion
      intensities among quality control runs.

PMID- 24564983
TI  - Enhancement of accuracy and efficiency for RNA secondary structure prediction by
      sequence segmentation and MapReduce.
AB  - BACKGROUND: Ribonucleic acid (RNA) molecules play important roles in many
      biological processes including gene expression and regulation. Their secondary
      structures are crucial for the RNA functionality, and the prediction of the
      secondary structures is widely studied. Our previous research shows that cutting
      long sequences into shorter chunks, predicting secondary structures of the chunks
      independently using thermodynamic methods, and reconstructing the entire
      secondary structure from the predicted chunk structures can yield better accuracy
      than predicting the secondary structure using the RNA sequence as a whole. The
      chunking, prediction, and reconstruction processes can use different methods and
      parameters, some of which produce more accurate predictions than others. In this
      paper, we study the prediction accuracy and efficiency of three different
      chunking methods using seven popular secondary structure prediction programs that
      apply to two datasets of RNA with known secondary structures, which include both
      pseudoknotted and non-pseudoknotted sequences, as well as a family of viral
      genome RNAs whose structures have not been predicted before. Our modularized
      MapReduce framework based on Hadoop allows us to study the problem in a parallel
      and robust environment. RESULTS: On average, the maximum accuracy retention
      values are larger than one for our chunking methods and the seven prediction
      programs over 50 non-pseudoknotted sequences, meaning that the secondary
      structure predicted using chunking is more similar to the real structure than the
      secondary structure predicted by using the whole sequence. We observe similar
      results for the 23 pseudoknotted sequences, except for the NUPACK program using
      the centered chunking method. The performance analysis for 14 long RNA sequences
      from the Nodaviridae virus family outlines how the coarse-grained mapping of
      chunking and predictions in the MapReduce framework exhibits shorter turnaround
      times for short RNA sequences. However, as the lengths of the RNA sequences
      increase, the fine-grained mapping can surpass the coarse-grained mapping in
      performance. CONCLUSIONS: By using our MapReduce framework together with
      statistical analysis on the accuracy retention results, we observe how the
      inversion-based chunking methods can outperform predictions using the whole
      sequence. Our chunk-based approach also enables us to predict secondary
      structures for very long RNA sequences, which is not feasible with traditional
      methods alone.

PMID- 24564987
TI  - Human Wharton's jelly mesenchymal stem cells promote skin wound healing through
      paracrine signaling.
AB  - INTRODUCTION: The prevalence of nonhealing wounds is predicted to increase due to
      the growing aging population. Despite the use of novel skin substitutes and wound
      dressings, poorly vascularized wound niches impair wound repair. Mesenchymal stem
      cells (MSCs) have been reported to provide paracrine signals to promote wound
      healing, but the effect of human Wharton's jelly-derived MSCs (WJ-MSCs) has not
      yet been described in human normal skin. METHODS: Human WJ-MSCs and normal skin
      fibroblasts were isolated from donated umbilical cords and normal adult human
      skin. Fibroblasts were treated with WJ-MSC-conditioned medium (WJ-MSC-CM) or
      nonconditioned medium. RESULTS: Expression of genes involved in re
      epithelialization (transforming growth factor-beta2), neovascularization (hypoxia
      inducible factor-1alpha) and fibroproliferation (plasminogen activator inhibitor
      1) was upregulated in WJ-MSC-CM-treated fibroblasts (P<=0.05). WJ-MSC-CM enhanced
      normal skin fibroblast proliferation (P<=0.001) and migration (P<=0.05), and
      promoted wound healing in an excisional full-thickness skin murine model.
      CONCLUSIONS: Under our experimental conditions, WJ-MSCs enhanced skin wound
      healing in an in vivo mouse model.

PMID- 24564988
TI  - Immuno-electron microscopy of primary cell cultures from genetically modified
      animals in liquid by atmospheric scanning electron microscopy.
AB  - High-throughput immuno-electron microscopy is required to capture the protein
      protein interactions realizing physiological functions. Atmospheric scanning
      electron microscopy (ASEM) allows in situ correlative light and electron
      microscopy of samples in liquid in an open atmospheric environment. Cells are
      cultured in a few milliliters of medium directly in the ASEM dish, which can be
      coated and transferred to an incubator as required. Here, cells were imaged by
      optical or fluorescence microscopy, and at high resolution by gold-labeled immuno
      ASEM, sometimes with additional metal staining. Axonal partitioning of neurons
      was correlated with specific cytoskeletal structures, including microtubules,
      using primary-culture neurons from wild type Drosophila, and the involvement of
      ankyrin in the formation of the intra-axonal segmentation boundary was studied
      using neurons from an ankyrin-deficient mutant. Rubella virus replication
      producing anti-double-stranded RNA was captured at the host cell's plasma
      membrane. Fas receptosome formation was associated with clathrin internalization
      near the surface of primitive endoderm cells. Positively charged Nanogold clearly
      revealed the cell outlines of primitive endoderm cells, and the cell division of
      lactic acid bacteria. Based on these experiments, ASEM promises to allow the
      study of protein interactions in various complexes in a natural environment of
      aqueous liquid in the near future. 

PMID- 24564990
TI  - Low adenosine triphosphate activity in CD4+ cells predicts infection in patients
      with lupus nephritis.
AB  - OBJECTIVES: The ImmuKnow (Cylex) assay has been reported to predict the risk of
      infection in some diseases; however, it is uncertain whether ImmuKnow can predict
      the risk of infection in lupus nephritis (LN) patients receiving
      immunosuppressive therapy. METHODS: The ImmuKnow Immune Cell Function Assay
      (Cylex, Inc., Columbia, MD, USA) was applied to measure the activity of CD4+ T
      cells, as a marker of global immune-competence. The correlation between changes
      in T cell activation and the relative risk of over-immunosuppression as well as
      infection was studied. The amount of adenosine triphosphate (ATP) produced by
      CD4+ T cells in response to phytohemagglutinin (PHA) was measured for 74 LN
      patients without infection, 22 LN patients with severe infection (i.e. required
      hospitalisation), and 28 healthy controls. RESULTS: No correlation was found
      between the ATP level and systemic lupus erythematosus (SLE) activity. The mean
      ATP level was significantly lower in LN patients with infection than that in
      healthy controls (p<0.01) and non-infected LN patients (p<0.01). The mean ATP
      level in non-infected LN patients was not significantly different compared to
      healthy controls. A cut-off ATP value of 300 ng/mL predicted infection in LN
      patients with a specificity of 77% and a sensitivity of 77%. Multi-variable
      partial correlation coefficient between the ATP assay and severe infection was r
      =-0.040, p<0.001; CRP was r=0.962, p<0.001. CONCLUSIONS: The ImmuKnow assay may
      be effective in identifying an increased risk of infection in LN patients but is
      not correlated with SLE activity. Combined CRP value will increase the diagnostic
      rate of severe infection in SLE. Larger studies are required to establish
      clinical advantages of this assay in SLE treatment.

PMID- 24564989
TI  - Gene and isoform expression signatures associated with tumor stage in kidney
      renal clear cell carcinoma.
AB  - BACKGROUND: Identification of expression alternations between early and late
      stage cancers is helpful for understanding cancer development and progression.
      Much research has been done focusing on stage-dependent gene expression profiles.
      In contrast, relatively fewer studies on isoform expression profiles have been
      performed due to the difficulty of quantification and noisy splicing. Here we
      conducted both gene- and isoform-level analysis on RNA-seq data of 234 stage I
      and 81 stage IV kidney renal clear cell carcinoma patients, aiming to uncover the
      stage-dependent expression signatures and investigate the advantage of isoform
      expression profiling for identifying advanced stage cancers and predicting
      clinical outcome. RESULTS: Both gene and isoform expression signatures are useful
      for distinguishing cancer stages. They provide common and unique information
      associated with cancer progression and metastasis. Combining gene and isoform
      signatures even improves the classification performance and reveals additional
      important biological processes, such as angiogenesis and TGF--beta signaling
      pathway. Moreover, expression abundance of a number of genes and isoforms is
      predictive of the risk of cancer death in an independent dataset, such as gene
      and isoform expression of ITPKA, the expression of a functional important isoform
      of UPS19. CONCLUSION: Isoform expression profiling provides unique and important
      information which cannot be detected by gene expression profiles. Combining gene
      and isoform expression signatures helps to identify advanced stage cancers,
      predict clinical outcome, and present a comprehensive view of cancer development
      and progression.

PMID- 24564991
TI  - [Chronic myeloid leukemia treatment and human immunodeficiency virus infection].

PMID- 24564992
TI  - [Gitelman's syndrome: a wolf in sheep's clothing].

PMID- 24564993
TI  - Natural history of venous thromboembolism in patients from the Mediterranean
      region. A systematic review.
AB  - BACKGROUND: Patients with cardiovascular diseases living in the Mediterranean
      area have a better outcome than those in other parts of the world, but it is not
      known whether these differences also occur with venous thromboembolism (VTE).
      METHODS: We searched the Medline and EMBASE databases to identify clinical trials
      and cohort studies of patients with VTE who had been treated with anticoagulant
      therapy for 3 months. Two reviewers independently extracted the data in a
      standardized manner. A total of 24 studies that included 7,225 patients (2,414
      from the Mediterranean region and 4,811 from other regions) were analyzed.
      RESULTS: The patients from the Mediterranean area were predominately women and
      older, and the idiopathic VTE was less frequent than in other regions. Compared
      with patients from other regions, patients from the Mediterranean region had an
      increased rate of recurrent deep vein thrombosis (4.35% vs. 2.68%; odds ratio
      [OR], 1.65; 95% confidence interval [95% CI] 1.27-2.15), fatal recurrent VTE
      (0.75% vs. 0.35%; OR, 2.11; 95% CI 1.09-4.12) and fatal bleeding (0.25% vs.
      0.06%; odds ratio: 3.99; 95% CI 1.00-16.0). The case-fatality rate (CFR) for
      recurrent VTE was 12.8% (95% CI 7.99-19.1) in the Mediterranean region and 8.41%
      (5.15-12.9) in other areas. The CFR for major bleeding was 11.3% (95% CI 4.72
      22.1) and 3.22% (95% CI 0.83-8.53), respectively. CONCLUSIONS: Compared to other
      regions, patients with VTE from the Mediterranean region have greater mortality
      during the first 3 months of treatment due to a greater incidence of recurrent
      VTE and severe hemorrhaging.

PMID- 24564994
TI  - Crimean-Congo hemorrhagic fever among health care workers, Turkey.
AB  - We investigated 9 cases of Crimean-Congo hemorrhagic fever (1 fatal, 2
      asymptomatic) among health care workers in Turkey. Needlestick injuries were
      reported for 4 workers. Eight received ribavirin. In addition to standard
      precautions, airborne infection isolation precautions are essential during
      aerosol-generating procedures. For postexposure prophylaxis and therapy,
      ribavirin should be given. 

PMID- 24564995
TI  - Three-dimensional osteochondral microtissue to model pathogenesis of
      osteoarthritis.
AB  - Osteoarthritis (OA), the most prevalent form of arthritis, affects up to 15% of
      the adult population and is principally characterized by degeneration of the
      articular cartilage component of the joint, often with accompanying subchondral
      bone lesions. Understanding the mechanisms underlying the pathogenesis of OA is
      important for the rational development of disease-modifying OA drugs. While most
      studies on OA have focused on the investigation of either the cartilage or the
      bone component of the articular joint, the osteochondral complex represents a
      more physiologically relevant target because the disease ultimately is a disorder
      of osteochondral integrity and function. In our current investigation, we are
      constructing an in vitro three-dimensional microsystem that models the structure
      and biology of the osteochondral complex of the articular joint. Osteogenic and
      chondrogenic tissue components are produced using adult human mesenchymal stem
      cells derived from bone marrow and adipose seeded within biomaterial scaffolds
      photostereolithographically fabricated with defined internal architecture. A
      three-dimensional-printed, perfusion-ready container platform with dimensions to
      fit into a 96-well culture plate format is designed to house and maintain the
      osteochondral microsystem that has the following features: an anatomic
      cartilage/bone biphasic structure with a functional interface; all tissue
      components derived from a single adult mesenchymal stem cell source to eliminate
      possible age/tissue-type incompatibility; individual compartments to constitute
      separate microenvironment for the synovial and osseous components; accessible
      individual compartments that may be controlled and regulated via the introduction
      of bioactive agents or candidate effector cells, and tissue/medium sampling and
      compositional assays; and compatibility with the application of mechanical load
      and perturbation. The consequences of mechanical injury, exposure to inflammatory
      cytokines, and compromised bone quality on degenerative changes in the cartilage
      component are examined in the osteochondral microsystem as a first step towards
      its eventual application as an improved and high-throughput in vitro model for
      prediction of efficacy, safety, bioavailability, and toxicology outcomes for
      candidate disease-modifying OA drugs. 

PMID- 24564997
TI  - MicroRNA identification using linear dimensionality reduction with explicit
      feature mapping.
AB  - BACKGROUND: microRNAs are a class of small RNAs, about 20 nt long, which regulate
      cellular processes in animals and plants. Identifying microRNAs is one of the
      most important tasks in gene regulation studies. The main features used for
      identifying these tiny molecules are those in hairpin secondary structures of pre
      microRNA. RESULTS: A new classifier is employed to identify precursor microRNAs
      from both pseudo hairpins and other non-coding RNAs. This classifier achieves a
      geometric mean Gm = 92.20% with just three features and 92.91% with seven
      features. CONCLUSION: This study shows that linear dimensionality reduction
      combined with explicit feature mapping, namely miLDR-EM, achieves high
      performance in classification of microRNAs from other sequences. Also, explicitly
      mapping data onto a high dimensional space could be a useful alternative to
      kernel-based methods for large datasets with a small number of features.
      Moreover, we demonstrate that microRNAs can be accurately identified by just
      using three properties that involve minimum free energy.

PMID- 24564996
TI  - Circulating MMP11 and specific antibody immune response in breast and prostate
      cancer patients.
AB  - BACKGROUND: Tumor Associated Antigens are characterized by spontaneous immune
      response in cancer patients as a consequence of overexpression and epitope
      presentation on MHC class I/II machinery. Matrix Metalloprotease 11 (MMP11)
      expression has been associated with poor prognosis for several cancer types,
      including breast and prostate cancer. METHODS: MMP11 expression was determined by
      immunoistochemistry in breast and prostate cancer samples. Circulating MMP11
      protein as well as the spontaneous immune responses against MMP11 were analyzed
      in a set of breast and prostate cancer patients. RESULTS: In plasma samples MMP11
      protein was present in 5/13 breast cancer patients and in 1/12 prostate cancer
      patients. An antibody response was observed in 7/13 breast cancer patients and in
      3/12 prostate cancer patients. CONCLUSIONS: These findings further suggest MMP11
      as a promising biomarker for these tumor types and a suitable target for cancer
      immunotherapy strategies.

PMID- 24564998
TI  - Joint effect of alexithymia and mood on the categorization of nonverbal emotional
      vocalizations.
AB  - The role of stable factors, such as alexithymia (i.e., difficulties identifying
      and expressing feelings, externally oriented cognitive style), or temporary
      factors, such as affective states (mood), on emotion perception has been widely
      investigated in the literature. However, little is known about the separate or
      joint effect of the alexithymia level and affective states (positive affectivity,
      negative affectivity) on the recognition of nonverbal emotional vocalizations
      (NEV) (e.g., laughs, cries, or sighs). In this study, participants had to
      categorize NEV communicating 10 emotions by selecting the correct verbal
      emotional label. Results show that the level of alexithymia is negatively
      correlated to the capacity to accurately categorize negative vocalizations, and
      more particularly sad NEV. On the other hand, negative affectivity appeared
      negatively correlated with the ability to accurately categorize NEV in general,
      and negative vocalizations in particular. After splitting the results by the
      alexithymia level (high vs. low scorers), significant associations between mood
      and accuracy rates were found in the group of high alexithymia scorers only.
      These findings support the idea that alexithymic features act across sensory
      modalities and suggest a mood-interference effect that would be stronger in those
      individuals. 

PMID- 24564999
TI  - Anhedonia in obsessive-compulsive disorder: beyond comorbid depression.
AB  - Obsessive-compulsive disorder (OCD) has been linked to reward dysfunctions,
      highlighting a possible role of anhedonia in OCD. Surprisingly, anhedonia in OCD
      has never been evaluated. Moreover, although nicotine typically has anti
      anhedonic effects, anecdotal reports suggest low prevalence rates of smoking in
      OCD. To address these two phenomena, 113 individuals with OCD completed a battery
      of questionnaires assessing symptom severity, anhedonia, and smoking. 28.3% of
      the sample met criteria for clinically significant anhedonia, which correlated
      with Y-BOCS scores (r=0.44), even when controlling for depressive symptoms. 13.3%
      of the sample endorsed current smoking, a lower rate than seen in psychiatric
      disorders (40-90%) and the general adult population (19%). Results highlight high
      rates of anhedonia and yet reduced prevalence of smoking in OCD. In contrast to
      the known positive association between anhedonia and smoking, a negative
      association emerged. Future research is needed to address the unique interface
      between anhedonia and reward responsiveness in OCD. Potential clinical
      implications are discussed. 

PMID- 24565000
TI  - Role of C-reactive protein in schizophrenia: an overview.
AB  - Over the years, schizophrenia is speculated to be associated with immune or
      inflammatory reactions mediated by cytokines. It is proposed that chronic
      inflammation might damage the micro-vascular system of brain and hamper cerebral
      blood flow. Scientific evidence suggests that an increase of stress hormone like
      norepinephrine may activate the inflammatory arm of the immune system and trigger
      the expression of genes that cause chronic, low-grade inflammation. Thus, studies
      were conducted to decipher the potentiality of CRP as a marker for inflammation
      in schizophrenia. This article reviews the findings of CRP in schizophrenia, and
      the limitations of the previous studies have been discussed. The importance of
      simultaneous study of CRP modulating cytokines and CRP gene polymorphism in the
      study of serum or plasma level of CRP has been emphasized. 

PMID- 24565001
TI  - Weighted set enrichment of gene expression data.
AB  - BACKGROUND: Sets of genes that are known to be associated with each other can be
      used to interpret microarray data. This gene set approach to microarray data
      analysis can illustrate patterns of gene expression which may be more informative
      than analyzing the expression of individual genes. Various statistical approaches
      exist for the analysis of gene sets. There are three main classes of these
      methods: over-representation analysis, functional class scoring, and pathway
      topology based methods. METHODS: We propose weighted hypergeometric and weighted
      chi-squared methods in order to assign a rank to the degree to which each gene
      participates in the enrichment. Each gene is assigned a weight determined by the
      absolute value of its log fold change, which is then raised to a certain power.
      The power value can be adjusted as needed. Datasets from the Gene Expression
      Omnibus are used to test the method. The significantly enriched pathways are
      validated through searching the literature in order to determine their relevance
      to the dataset. RESULTS: Although these methods detect fewer significantly
      enriched pathways, they can potentially produce more relevant results.
      Furthermore, we compare the results of different enrichment methods on a set of
      microarray studies all containing data from various rodent neuropathic pain
      models. DISCUSSION: Our method is able to produce more consistent results than
      other methods when evaluated on similar datasets. It can also potentially detect
      relevant pathways that are not identified by the standard methods. However, the
      lack of biological ground truth makes validating the method difficult.

PMID- 24565003
TI  - Antiproliferative effect of Canavalia brasiliensis lectin on B16F10 cells.
AB  - Lectins are proteins or glycoproteins with the ability to link to carbohydrates
      at the cell surface in a specific and reversible manner. Studies have showed that
      lectins are demonstrate immunomodulatory and antitumor agents. This study aims to
      evaluate the effect of lectin extracted from the seeds of Canavalia brasiliensis
      (ConBr) on murine melanoma B16F10 cells by analyzing cell viability, apoptosis
      index, cell migration, production of cytokines and nitric oxide (NO). Results
      showed that ConBr was able to reduce cell viability and thwart apoptosis, which
      could be observed by decrease in cell migration. ConBr also induced NO and IL-12
      synthesis. Altogether, these data demonstrate the potential of ConBr as a
      therapeutic agent for melanoma. 

PMID- 24565004
TI  - Clinical pharmacology of eating and not eating.
AB  - FDA approval of Belviq and Qsymia seems to suggest that novel pharmacological
      targets to modulate human abnormal eating behaviours are still to be identified.
      However, a renewed translational approach opens new avenues on eating disorders
      and female vulnerability, highlighting the role of our reward pathway in obesity
      and binge eating and leading to potential novel targets. Nevertheless, the 'food
      addiction' hypothesis is still causing much scientific debate. In this context
      the interest in the modulation of ghrelin pathway is still very high although, so
      far, only ghrelin agonism has confirmed its therapeutic potential in cachectic
      patients. Unfortunately, ghrelin modulation does not offer a therapeutic option
      for Anorexia Nervosa, where novel promising pharmacological treatments are still
      to be uncovered. 

PMID- 24565002
TI  - Inflammatory cytokines induce a reduction in E-cadherin expression and
      morphological changes in MDCK cells.
AB  - Epithelial-mesenchymal transition (EMT) is a fundamental phenomenon in organisms
      that occurs during gastrulation, wound healing, and cancer metastasis. Various
      cytokines induce EMT processes through complex mechanisms. Inflammatory
      cytokines, such as tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL
      6), induce EMT in human cell lines. However, whether inflammatory cytokines can
      affect EMT processes in canine cell lines remains unclear. In this study, we
      investigated the role of transforming growth factor beta (TGF-beta), TNF-alpha,
      and IL-6 in Madin-Darby canine kidney (MDCK) cells. We found that the
      localization of E-cadherin, a cell adhesion molecule, was shifted and that its
      expression was decreased. We also observed morphological changes in MDCK cells
      under persistent stimulation of inflammatory cytokines. Morphological changes in
      cells may occur during late stages of EMT processes; inflammatory cytokines may
      be important in these changes. 

PMID- 24565005
TI  - Clinical pharmacology in the development of new antidepressants: the challenges.
AB  - Given the lack of fundamental knowledge about the causes and pathophysiology of
      depression, it is a challenge for Phase I in antidepressant development to
      efficiently and thoroughly test new drugs. Initiation of Phase I should always be
      preceded by a careful consideration of what is known about the target and the
      molecule. While some early indicators of efficacy, such as the Emotional Test
      Battery, EEG markers, and fMRI correlates of anhedonia are available, further
      work is needed for their full incorporation in Phase I. Phase I studies of
      antidepressants should incorporate new measures and methods to the extent
      possible, and have the freedom to explore new hypotheses and move beyond the
      predetermined and inflexible study designs of traditional Phase I studies. 

PMID- 24565006
TI  - Multiple mechanisms have been tested in pain--how can we improve the chances of
      success?
AB  - Recent advances in understanding the pathophysiology of pain have led to a wealth
      of molecular targets for novel analgesic drugs and many clinical drug trials.
      There have been successes, like the gabapentinoids for neuropathic pain and
      calcium channel blockers for otherwise intractable pain states; and drugs which
      show promise in clinical trials, like nerve growth factor inhibitors and p38
      kinase inhibitors. Unfortunately there have also been a number of failures. We
      suggest factors which might predispose to success, for example some clinical
      precedence for the mechanism in pain or a genetic link for the mechanism, for
      example a mutation linked to a pain syndrome. We also stress the importance of
      demonstrating molecular target engagement with a novel compound and suggest pain
      biomarkers which can be used for mechanistic drug profiling. 

PMID- 24565008
TI  - Use of predictive models in CNS diseases.
AB  - Today the CNS drug development poses serious challenges for developers given the
      low probability of success and the disproportionately high investment costs. This
      review demonstrates how predictive models can provide quantitative criteria for
      increasing the efficiency of drug development in CNS. Predictive models can be
      applied to characterize, understand, and predict a drug's PK and PD behavior; to
      quantify uncertainty of information about that behavior; to identify factors that
      could affect the outcomes of a clinical trial through Clinical Trial Simulation
      (CTS), to identify prognostic factors that could affect the disease progression,
      to implement optimal and adaptive clinical trial and finally to control the level
      of placebo response by implementing study designs that minimizes the impact of
      placebo on study outcomes. 

PMID- 24565007
TI  - Preventing cognitive decline in preclinical Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a chronic neurodegenerative disease leading to
      cognitive decline, dementia, and ultimately death. Despite extensive R&D efforts,
      there are no diseases modifying treatments for AD available. The stage in which
      patients receive a clinical diagnosis of probable AD may be too late for disease
      modifying pharmacotherapy. Prevention strategies may be required to successfully
      tackle AD. Preclinical AD applies to over half of all healthy elderly subjects
      and manifests by signs of amyloid deposition and/or neuronal injury in the brain,
      preceding the stage in which symptoms of dementia, cognitive and functional
      impairment become observable. Prevention trials in preclinical AD require longer
      and larger clinical trials using biomarkers and cognitive endpoints, which
      requires collaboration across academia, government and industry. 

PMID- 24565009
TI  - Understanding the pharmacology of headache.
AB  - Migraine continues to be the most common of the debilitating headaches. Existing
      acute headache treatments are not always satisfactory, and current research is
      focussed on targeting neuroinflammatory pathways with drugs that are devoid of
      vascular action. Current prophylactic drugs are largely centred around
      antihypertensive, anticonvulsant and antidepressant drugs, although not all drugs
      of all sub-classes in these categories are effective. Selective agents which
      target the neuroinflammatory process including targets such as calcitonin gene
      related peptide, and PANNEXIN 1 may have clinical utility. 

PMID- 24565010
TI  - Understanding the pharmacology of stroke and multiple sclerosis through imaging.
AB  - Stroke and multiple sclerosis (MS) illustrate how clinical imaging can facilitate
      early phase drug development and most effective medicine use in the clinic.
      Imaging has enhanced understanding of the dynamics of evolution of disease
      pathophysiology, better defining treatment targets. Imaging measures can enable
      stratification of patients for clinical trials and for most cost-effective use in
      the clinic. In MS, imaging has allowed smaller Phase II clinical trials and
      contributed to medicine differentiation. It also has led to consideration of
      suppression of inflammation and neurodegeneration as meaningfully distinct
      pharmacodynamic concepts. Similar imaging measures can be used in preclinical and
      clinical studies. Testing translational pharmacological hypotheses using clinical
      imaging more explicitly could improve the success of the next generation of
      stroke therapeutics. 

PMID- 24565011
TI  - Pharmacologically, are smokers the same as non-smokers?
AB  - Growing evidence suggests that there are subpopulations of daily smokers ranging
      from light infrequent users to heavy daily users. In the present review we will
      investigate whether these differences can be explained by factors such as social
      context, responsiveness to environmental cues, personality traits, neurochemical
      and pharmacogenetic differences. We will also assess how controlled abstinence
      and free choice smoking paradigms in a human laboratory setting may help identify
      and characterize these differences and what can be learned from these models to
      accurately predict clinical efficacy in the later phase testing of new chemical
      entities for the treatment of smoking dependence. 

PMID- 24565012
TI  - Clinical pharmacology in neuroscience drug discovery: quo vadis?
AB  - Clinical Pharmacology in Neuroscience Drug Discovery in recent years has
      concentrated on First Time in Human safety and pharmacokinetics. The more
      traditional pharmacological research in humans has been reduced mainly as a
      response to the difficulty of developing human pharmacology models in
      neuroscience diseases. As a consequence, opportunities are being missed to aid in
      target selection and in target validation. The decision of big Pharma to reduce
      investment from the Neurosciences has had implications for clinical
      pharmacologists in this area. It remains to be seen whether academia, government
      laboratories and contract houses will respond to the challenge of carrying out
      increased Clinical Pharmacology in the Neurosciences. 

PMID- 24565013
TI  - Increasing pharmacological knowledge about human neurological and psychiatric
      disorders through functional neuroimaging and its application in drug discovery.
AB  - Functional imaging methods such as fMRI have been widely used to gain greater
      understanding of brain circuitry abnormalities in CNS disorders and their
      underlying neurochemical basis. Findings suggest that: (1) drugs with known
      clinical efficacy have consistent effects on disease relevant brain circuitry,
      (2) brain activation changes at baseline or early drug effects on brain activity
      can predict long-term efficacy; and (3) fMRI together with pharmacological
      challenges could serve as experimental models of disease phenotypes and be used
      for screening novel drugs. Together, these observations suggest that drug related
      modulation of disease relevant brain circuitry may serve as a promising
      biomarker/method for use in drug discovery to demonstrate target engagement,
      differential efficacy, dose-response relationships, and prediction of clinically
      relevant changes. 

PMID- 24565014
TI  - The role of human cognitive neuroscience in drug discovery for the dementias.
AB  - Cognitive dysfunction characterizes all the various forms of dementia. Evidence
      is accumulating that all of the progressive neurodegenerative dementias, such as
      Alzheimer's disease (AD), are preceded by years, if not decades, of pathological
      cognitive decline. The limited effectiveness of the four current medications
      registered for AD together with the failure of dozens of programmes over the last
      decade has influenced the decision to evaluate treatment at earlier stages of the
      disease; even before any cognitive symptoms have appeared. However, it has to be
      acknowledged that treating mild cognitive impairment (MCI) as a prodrome for AD
      has also had very limited success. Nonetheless a more important problem in MCI
      research, and dementia in general, has to be laid at the door of the limited
      effectiveness of the cognitive tests employed. This problem will become even more
      severe for the latest research direction of treating preclinical AD because such
      individuals will have levels of cognitive abilities which are in the normal
      range; and thus many of the scales currently used in dementia research will not
      be sufficiently demanding to identify change over time. This paper reviews and
      discusses the methodology and instruments available for research and clinical
      practice in this major area; with a focus on the challenges involved in test
      selection and evaluation. 

PMID- 24565015
TI  - Experiments with cocaine and heroin addicts--are they predictive?
AB  - Treating cocaine addiction using dopamine replacement strategies, treats
      withdrawal but not relapse. Experiments with diverse pharmacological agents shows
      involvement of multiple pharmacologies and new approaches are emerging to treat
      the drug seeking behaviour and craving associated with relapse. Neuropathological
      studies are showing structural and connectivity changes in the brain of addicts
      which appear permanent, making control of learned behaviours associated with
      these changes extremely challenging. Heroin addiction is treated successfully
      with opiate replacement strategies but relapse and switch to other drugs of abuse
      remains. Combination therapies are partially successful in treating co-abused
      substances but do little to the heroin relapse rate. As with cocaine, attention
      is shifting to understanding the neuropathological changes, particularly in the
      pre-frontal cortex and hippocampus. 

PMID- 24565016
TI  - New applications of disease genetics and pharmacogenetics to drug development.
AB  - TOMMORROW is a Phase III delay of onset clinical trial to determine whether low
      doses of pioglitazone, a molecule that induces mitochondrial doubling, delays the
      onset of MCI-AD in normal subjects treated with low dose compared to placebo.
      BOLD imaging studies in rodents and man were used to find the dose that increases
      oxygen consumption at central regions of the brain in higher proportion than
      activation of large corticol regions. The trial is made practical by the use of a
      pharmacogenetic algorithm based on TOMM40 and APOE genotypes and age to identify
      normal subjects at high risk of MCI-AD between the ages of 65-83 years within a
      five year follow-up period. 

PMID- 24565017
TI  - A computational method for predicting regulation of human microRNAs on the
      influenza virus genome.
AB  - BACKGROUND: While it has been suggested that host microRNAs (miRNAs) may
      downregulate viral gene expression as an antiviral defense mechanism, such a
      mechanism has not been explored in the influenza virus for human flu studies. As
      it is difficult to conduct related experiments on humans, computational studies
      can provide some insight. Although many computational tools have been designed
      for miRNA target prediction, there is a need for cross-species prediction,
      especially for predicting viral targets of human miRNAs. However, finding
      putative human miRNAs targeting influenza virus genome is still challenging.
      RESULTS: We developed machine-learning features and conducted comprehensive data
      training for predicting interactions between H1N1 genome segments and host miRNA.
      We defined our seed region as the first ten nucleotides from the 5' end of the
      miRNA to the 3' end of the miRNA and integrated various features including the
      number of consecutive matching bases in the seed region of 10 bases, a triplet
      feature in seed regions, thermodynamic energy, penalty of bulges and wobbles at
      binding sites, and the secondary structure of viral RNA for the prediction.
      CONCLUSIONS: Compared to general predictive models, our model fully takes into
      account the conservation patterns and features of viral RNA secondary structures,
      and greatly improves the prediction accuracy. Our model identified some key
      miRNAs including hsa-miR-489, hsa-miR-325, hsa-miR-876-3p and hsa-miR-2117, which
      target HA, PB2, MP and NS of H1N1, respectively. Our study provided an
      interesting hypothesis concerning the miRNA-based antiviral defense mechanism
      against influenza virus in human, i.e., the binding between human miRNA and viral
      RNAs may not result in gene silencing but rather may block the viral RNA
      replication.

PMID- 24565019
TI  - Complex realities: community engagement for a paediatric randomized controlled
      malaria vaccine trial in Kilifi, Kenya.
AB  - BACKGROUND: Community engagement (CE) is increasingly promoted for biomedical
      research conducted in resource poor settings for both intrinsic and instrumental
      purposes. Given the potential importance of CE, but also complexities and
      possibility of unexpected negative outcomes, there is need for more documentation
      of CE processes in practice. We share experiences of formal CE for a paediatric
      randomized controlled malaria vaccine trial conducted in three sites within
      Kilifi County, Kenya. METHODS: Social scientists independent of the trial held in
      depth individual interviews with trial researchers (n=5), community leaders (n=8)
      and parents (15 with enrolled children and 4 without); and group discussions with
      fieldworkers (n=6) and facility staff (n=2). We conducted a survey of
      participating households (n=200) and observed over 150 CE activities. RESULTS:
      The overall CE plan was similar across the three study sites, although less
      community-based information in site C. Majority perceived CE activities to clear
      pre-existing concerns and misconceptions; increase visibility, awareness of and
      trust in trial staff. Challenges included: some community leaders attempting to
      exert pressure on people to enrol; local wording in information sheets and
      consent forms feeding into serious anxieties about the trial; and concerns about
      reduced CE over time. Negative effects of these challenges were mitigated through
      changes to on-going CE activities, and final information sharing and consent
      being conducted individually by trained clinical staff. One year after enrolment,
      31% (n = 62) of participants' parents reported malaria prevention as the main aim
      of the activities their children were involved in, and 93% wanted their children
      to remain involved. CONCLUSION: The trial teams' goals for CE were relatively
      clear from the outset. Other actors' hopes and expectations (like higher
      allowances and future employment) were not openly discussed, but emerged over the
      course of engagements. Encouraging open discussion of all actors' intentions and
      goals from the outset takes time, risks raising expectations that cannot be met,
      and is complex. However, doing so in future similar trials may allow successes
      here to be built upon, and some challenges minimized or avoided. TRIAL
      REGISTRATION: ClinicalTrials.gov NCT00866619 (registration 19-Mar-2009).

PMID- 24565018
TI  - A novel mycobacterial Hsp70-containing fusion protein targeting mesothelin
      augments antitumor immunity and prolongs survival in murine models of ovarian
      cancer and mesothelioma.
AB  - BACKGROUND: Although dendritic cell (DC) vaccines are considered to be promising
      treatments for advanced cancer, their production and administration is costly and
      labor-intensive. We developed a novel immunotherapeutic agent that links a single
      chain antibody variable fragment (scFv) targeting mesothelin (MSLN), which is
      overexpressed on ovarian cancer and mesothelioma cells, to Mycobacterium
      tuberculosis (MTB) heat shock protein 70 (Hsp70), which is a potent immune
      activator that stimulates monocytes and DCs, enhances DC aggregation and
      maturation and improves cross-priming of T cells mediated by DCs. METHODS:
      Binding of this fusion protein with MSLN on the surface of tumor cells was
      measured by flow cytometry and fluorescence microscopy. The therapeutic efficacy
      of this fusion protein was evaluated in syngeneic and orthotopic mouse models of
      papillary ovarian cancer and malignant mesothelioma. Mice received 4
      intraperitoneal (i.p.) treatments with experimental or control proteins post i.p.
      injection of tumor cells. Ascites-free and overall survival time was measured.
      For the investigation of anti-tumor T-cell responses, a time-matched study was
      performed. Splenocytes were stimulated with peptides, and IFNgamma- or Granzyme B
      generating CD3+CD8+ T cells were detected by flow cytometry. To examine the role
      of CD8+ T cells in the antitumor effect, we performed in vivo CD8+ cell
      depletion. We further determined if the fusion protein increases DC maturation
      and improves antigen presentation as well as cross-presentation by DCs. RESULTS:
      We demonstrated in vitro that the scFvMTBHsp70 fusion protein bound to the tumor
      cells used in this study through the interaction of scFv with MSLN on the surface
      of these cells, and induced maturation of bone marrow-derived DCs. Use of this
      bifunctional fusion protein in both mouse models significantly enhanced survival
      and slowed tumor growth while augmenting tumor-specific CD8+ T-cell dependent
      immune responses. We also demonstrated in vitro and in vivo that the fusion
      protein enhanced antigen presentation and cross-presentation by targeting tumor
      antigens towards DCs. CONCLUSIONS: This new cancer immunotherapy has the
      potential to be cost-effective and broadly applicable to tumors that overexpress
      mesothelin.

PMID- 24565020
TI  - A population-based evolutionary search approach to the multiple minima problem in
      de novo protein structure prediction.
AB  - BACKGROUND: Elucidating the native structure of a protein molecule from its
      sequence of amino acids, a problem known as de novo structure prediction, is a
      long standing challenge in computational structural biology. Difficulties in
      silico arise due to the high dimensionality of the protein conformational space
      and the ruggedness of the associated energy surface. The issue of multiple minima
      is a particularly troublesome hallmark of energy surfaces probed with current
      energy functions. In contrast to the true energy surface, these surfaces are
      weakly-funneled and rich in comparably deep minima populated by non-native
      structures. For this reason, many algorithms seek to be inclusive and obtain a
      broad view of the low-energy regions through an ensemble of low-energy (decoy)
      conformations. Conformational diversity in this ensemble is key to increasing the
      likelihood that the native structure has been captured. METHODS: We propose an
      evolutionary search approach to address the multiple-minima problem in decoy
      sampling for de novo structure prediction. Two population-based evolutionary
      search algorithms are presented that follow the basic approach of treating
      conformations as individuals in an evolving population. Coarse graining and
      molecular fragment replacement are used to efficiently obtain protein-like child
      conformations from parents. Potential energy is used both to bias parent
      selection and determine which subset of parents and children will be retained in
      the evolving population. The effect on the decoy ensemble of sampling minima
      directly is measured by additionally mapping a conformation to its nearest local
      minimum before considering it for retainment. The resulting memetic algorithm
      thus evolves not just a population of conformations but a population of local
      minima. RESULTS AND CONCLUSIONS: Results show that both algorithms are effective
      in terms of sampling conformations in proximity of the known native structure.
      The additional minimization is shown to be key to enhancing sampling capability
      and obtaining a diverse ensemble of decoy conformations, circumventing premature
      convergence to sub-optimal regions in the conformational space, and approaching
      the native structure with proximity that is comparable to state-of-the-art decoy
      sampling methods. The results are shown to be robust and valid when using two
      representative state-of-the-art coarse-grained energy functions.

PMID- 24565021
TI  - Clinical verification of a clinical decision support system for ventilator
      weaning.
AB  - BACKGROUND: Weaning is typically regarded as a process of discontinuing
      mechanical ventilation in the daily practice of an intensive care unit (ICU).
      Among the ICU patients, 39%-40% need mechanical ventilator for sustaining their
      lives. The predictive rate of successful weaning achieved only 35-60% for
      decisions made by physicians. Clinical decision support systems (CDSSs) are
      promising in enhancing diagnostic performance and improve healthcare quality in
      clinical setting. To our knowledge, a prospective study has never been conducted
      to verify the effectiveness of the CDSS in ventilator weaning before. In this
      study, the CDSS capable of predicting weaning outcome and reducing duration of
      ventilator support for patients has been verified. METHODS: A total of 380
      patients admitted to the respiratory care center of the hospital were randomly
      assigned to either control or study group. In the control group, patients were
      weaned with traditional weaning method, while in the study group, patients were
      weaned with CDSS monitored by physicians. After excluding the patients who
      transferred to other hospitals, refused further treatments, or expired the
      admission period, data of 168 and 144 patients in the study and control groups,
      respectively, were used for analysis. RESULTS: The results show that a
      sensitivity of 87.7% has been achieved, which is significantly higher (p<0.01)
      than the weaning determined by physicians (sensitivity: 61.4%). Furthermore, the
      days using mechanical ventilator for the study group (38.41 +/- 3.35) is
      significantly (p<0.001) shorter than the control group (43.69 +/- 14.89), with a
      decrease of 5.2 days in average, resulting in a saving of healthcare cost of
      NT$45,000 (US$1,500) per patient in the current Taiwanese National Health
      Insurance setting. CONCLUSIONS: The CDSS is demonstrated to be effective in
      identifying the earliest time of ventilator weaning for patients to resume and
      sustain spontaneous breathing, thereby avoiding unnecessary prolonged ventilator
      use and decreasing healthcare cost.

PMID- 24565022
TI  - Maintaining respect and fairness in the usage of stored shared specimens.
AB  - BACKGROUND: Every year, research specimens are shipped from one institution to
      another as well as across national boundaries. A significant proportion of
      specimens move from poor to rich countries. Concerns are always raised on the
      future usage of the stored specimens shipped to research institutions from
      developing countries. Creating awareness of the processes is required in all
      sectors involved in biomedical research. To maintain fairness and respect in
      sharing biomedical specimens and research products requires safeguarding by
      Ethics Review Committees in both provider and recipient institutions. Training in
      basic ethical principles in research is required to all sectors involved in
      biomedical research so as to level up the research playing field. DISCUSSION: By
      agreeing to provide specimens, individuals and communities from whom samples are
      collected would have placed their trust and all ensuing up-keep of the specimens
      to the researchers. In most collaborative set-up, laid down material transfer
      agreements are negotiated and signed before the shipment of specimens.
      Researchers, research ethics committees (RECs) and institutions in the countries
      of origin are supposed to serve as overseers of the specimens. There is need to
      advocate for honesty in sample handling and sharing, and also need to oversee any
      written commitments by researchers, RECs and institutions at source as well as in
      recipient institution. Commitments from source RECs and Institutional Review
      Boards (IRBs) and in the receiving institution on overseeing the future usage of
      stored specimens are required; including the ultimate confirmation abiding by the
      agreement. Training in ethical issues pertaining to sample handling and
      biomedical research in general is essential at all levels of academic pursuit.
      While sharing of biological specimens and research data demands honesty and
      oversight by ethical regulatory agents from both institutions in developing
      country and recipient institutions in developed countries. CONCLUDING SUMMARY:
      Archiving of biological specimens requires reconsideration for the future of
      biomedical findings and scientific break-throughs. Biomedical ethical regulations
      still need to established clear viable regulations that have vision for the
      future of science through shared and archived samples. This discussion covers and
      proposes essential points that need to be considered in view of future
      generations and scientific break-throughs. The discussion is based on the
      experience of working in resource-limited settings, the local regulatory laws and
      the need to refine research regulations governing sharing and storage of
      specimens for the future of science.

PMID- 24565023
TI  - Endothelial specific delivery of siRNA.

PMID- 24565024
TI  - Coming out ahead: the cost effectiveness of external cephalic version using
      spinal anesthesia.
AB  - Breech presentation is encountered in 3 to 4% of term pregnancies and has been a
      significant driver of the increased rate of cesarean deliveries over the last 4
      decades. External cephalic version (ECV) is recommended at term by most
      professional organizations in an effort to reduce the prospect of cesarean
      deliveries. The authors propose the use of regional anesthesia to increase
      efficacy and reduce cost in the care of patients who undergo ECV in an effort to
      convert a breech presentation to a vertex counterpart. Despite emerging evidence
      of the advantages, obstacles to more comprehensive implementation of this
      approach continue to exist, which include patient acceptance, provider
      experience, and safety concerns. The addition of tocolytics and use of regional
      anesthesia for secondary ECV efforts have also been considered as options to
      increase success and reduce cost. This is a commentary on
      http://www.ijhpr.org/content/3/1/5. 

PMID- 24565025
TI  - Inferring transcription factor collaborations in gene regulatory networks.
AB  - BACKGROUND: Living cells are realized by complex gene expression programs that
      are moderated by regulatory proteins called transcription factors (TFs). The TFs
      control the differential expression of target genes in the context of
      transcriptional regulatory networks (TRNs), either individually or in groups.
      Deciphering the mechanisms of how the TFs control the expression of target genes
      is a challenging task, especially when multiple TFs collaboratively participate
      in the transcriptional regulation. RESULTS: We model the underlying regulatory
      interactions in terms of the directions (activation or repression) and their
      logical roles (necessary and/or sufficient) with a modified association rule
      mining approach, called mTRIM. The experiment on Yeast discovered 670 regulatory
      interactions, in which multiple TFs express their functions on common target
      genes collaboratively. The evaluation on yeast genetic interactions, TF knockouts
      and a synthetic dataset shows that our algorithm is significantly better than the
      existing ones. CONCLUSIONS: mTRIM is a novel method to infer TF collaborations in
      transcriptional regulation networks. mTRIM is available at
      http://www.msu.edu/~jinchen/mTRIM.

PMID- 24565026
TI  - Influenza A(H1N1)pdm09 virus infection in giant pandas, China.
AB  - We confirmed infection with influenza A(H1N1)pdm09 in giant pandas in China
      during 2009 by using virus isolation and serologic analysis methods. This finding
      extends the host range of influenza viruses and indicates a need for increased
      surveillance for and control of influenza viruses among giant pandas. 

PMID- 24565027
TI  - Novel alternative splicing isoform biomarkers identification from high-throughput
      plasma proteomics profiling of breast cancer.
AB  - BACKGROUND: In the biopharmaceutical industry, biomarkers define molecular
      taxonomies of patients and diseases and serve as surrogate endpoints in early
      phase drug trials. Molecular biomarkers can be much more sensitive than
      traditional lab tests. Discriminating disease biomarkers by traditional method
      such as DNA microarray has proved challenging. Alternative splicing isoform
      represents a new class of diagnostic biomarkers. Recent scientific evidence is
      demonstrating that the differentiation and quantification of individual
      alternative splicing isoforms could improve insights into disease diagnosis and
      management. Identifying and characterizing alternative splicing isoforms are
      essential to the study of molecular mechanisms and early detection of complex
      diseases such as breast cancer. However, there are limitations with traditional
      methods used for alternative splicing isoform determination such as transcriptome
      level, low level of coverage and poor focus on alternative splicing. RESULTS:
      Therefore, we presented a peptidomics approach to searching novel alternative
      splicing isoforms in clinical proteomics. Our results showed that the approach
      has significant potential in enabling discovery of new types of high-quality
      alternative splicing isoform biomarkers. CONCLUSIONS: We developed a peptidomics
      approach for the proteomics community to analyze, identify, and characterize
      alternative splicing isoforms from MS-based proteomics experiments with more
      coverage and exclusive focus on alternative splicing. The approach can help
      generate novel hypotheses on molecular risk factors and molecular mechanisms of
      cancer in early stage, leading to identification of potentially highly specific
      alternative splicing isoform biomarkers for early detection of cancer.

PMID- 24565028
TI  - PhosSA: Fast and accurate phosphorylation site assignment algorithm for mass
      spectrometry data.
AB  - Phosphorylation site assignment of high throughput tandem mass spectrometry (LC
      MS/MS) data is one of the most common and critical aspects of phosphoproteomics.
      Correctly assigning phosphorylated residues helps us understand their biological
      significance. The design of common search algorithms (such as Sequest, Mascot
      etc.) do not incorporate site assignment; therefore additional algorithms are
      essential to assign phosphorylation sites for mass spectrometry data. The main
      contribution of this study is the design and implementation of a linear time and
      space dynamic programming strategy for phosphorylation site assignment referred
      to as PhosSA. The proposed algorithm uses summation of peak intensities
      associated with theoretical spectra as an objective function. Quality control of
      the assigned sites is achieved using a post-processing redundancy criteria that
      indicates the signal-to-noise ratio properties of the fragmented spectra. The
      quality assessment of the algorithm was determined using experimentally generated
      data sets using synthetic peptides for which phosphorylation sites were known. We
      report that PhosSA was able to achieve a high degree of accuracy and sensitivity
      with all the experimentally generated mass spectrometry data sets. The
      implemented algorithm is shown to be extremely fast and scalable with increasing
      number of spectra (we report up to 0.5 million spectra/hour on a moderate
      workstation). The algorithm is designed to accept results from both Sequest and
      Mascot search engines. An executable is freely available at
      http://helixweb.nih.gov/ESBL/PhosSA/ for academic research purposes. 

PMID- 24565029
TI  - New parameters for identifying subclinical atherosclerosis in patients with
      primary Sjogren's syndrome: a pilot study.
AB  - OBJECTIVES: We investigated sub-clinical cardiovascular involvement in primary
      Sjogren's syndrome (pSS) patients by means of ADMA, coronary flow reserve (CFR),
      intima media thickness (cIMT), pulse wave velocity (PWV) and myocardial
      deformation. METHODS: The study involved 22 outpatients with pSS (6 males, 16
      females; mean age 60.14+/-7.81 years) and no documentable cardiovascular disease,
      and 22 age- and gender-matched controls. Dipyridamole transthoracic stress
      echocardiography was used to evaluate wall motion and CFR. A CFR value of <2.5
      was considered a sign of impaired coronary function. We also evaluated cIMT
      arterial stiffness PWV and plasma ADMA levels, and made a speckle tracking
      echocardiography (STE) analysis. RESULTS: All of the patients were affected by
      pSS. Although within the normal range, the patients' CFR was lower than that of
      the controls (median 2.70; IQR 2.40-2.90 vs. 3.20; IQR 3.06-3.33; p<0.0001),
      whereas their ADMA levels were significantly higher (median 0.81 MUM; IQR 0.79
      0.85 MUM vs. 0.54 MUM; IQR 0.52-0.58 MUM; p<0.0001). Both left and right PWV
      values were significantly higher in the patients than in the controls (median 8.8
      m/s right and 8.9 m/s left vs. 6.86 and 6.89 m/s), whereas QIMT was substantially
      similar in the two groups. CONCLUSIONS: Higher ADMA levels suggest the presence
      of endothelial dysfunction and sub-clinical atherosclerosis in pSS patients, even
      in the case of a normal CFR. This finding is supported by the PWV values, which
      were higher in the pSS patients. ADMA levels and PWV values may be useful markers
      for identifying early endothelial dysfunction in pSS patients.

PMID- 24565030
TI  - The immunological and clinical effects of mutated ras peptide vaccine in
      combination with IL-2, GM-CSF, or both in patients with solid tumors.
AB  - BACKGROUND: Mutant Ras oncogenes produce proteins that are unique to cancer cells
      and represent attractive targets for vaccine therapy. We have shown previously
      that vaccinating cancer patients with mutant ras peptides is feasible and capable
      of inducing a specific immune response against the relevant mutant proteins.
      Here, we tested the mutant ras peptide vaccine administered in combination with
      low dose interleukin-2 (IL-2) or/and granulocyte-macrophage colony-stimulating
      factor (GM-CSF) in order to enhance the vaccine immune response. METHODS: 5000
      MUg of the corresponding mutant ras peptide was given subcutaneously (SQ) along
      with IL-2 (Arm A), GM-CSF (Arm B) or both (Arm C). IL-2 was given SQ at 6.0
      million IU/m2/day starting at day 5, 5 days/week for 2 weeks. GM-CSF was given SQ
      in a dose of 100 MUg/day one day prior to each ras peptide vaccination for 4
      days. Vaccines were repeated every 5 weeks on arm A and C, and every 4 weeks on
      arm B, for a maximum of 15 cycles or until disease progression. RESULTS: We
      treated 53 advanced cancer patients (38 with colorectal, 11 with pancreatic, 1
      with common bile duct and 3 with lung) on 3 different arms (16 on arm A, 18 on
      arm B, and 19 on arm C). The median progression free survival (PFS) and overall
      survival (OS) was 3.6 and 16.9 months, respectively, for all patients evaluable
      for clinical response (n = 48). There was no difference in PFS or OS between the
      three arms (P = 0.73 and 0.99, respectively). Most adverse events were grade 1-2
      toxicities and resolved spontaneously. The vaccine induced an immune response to
      the relevant ras peptide in a total of 20 out of 37 evaluable patients (54%) by
      ELISPOT, proliferative assay, or both. While 92.3% of patients on arm B had a
      positive immune response, only 31% of patients on arm A and 36% of patients on
      arm C had positive immune responses (P = 0.003, Fisher's exact test).
      CONCLUSIONS: The reported data showed that IL-2 might have a negative effect on
      the specific immune response induced by the relevant mutant ras vaccine in
      patients with advanced cancer. This observation deserves further investigations.
      TRIAL REGISTRATION: NCI97C0141.

PMID- 24565031
TI  - 16S rRNA metagenome clustering and diversity estimation using locality sensitive
      hashing.
AB  - BACKGROUND: Advances in biotechnology have changed the manner of characterizing
      large populations of microbial communities that are ubiquitous across several
      environments."Metagenome" sequencing involves decoding the DNA of organisms co
      existing within ecosystems ranging from ocean, soil and human body. Several
      researchers are interested in metagenomics because it provides an insight into
      the complex biodiversity across several environments. Clinicians are using
      metagenomics to determine the role played by collection of microbial organisms
      within human body with respect to human health wellness and disease. RESULTS: We
      have developed an efficient and scalable, species richness estimation algorithm
      that uses locality sensitive hashing (LSH). Our algorithm achieves efficiency by
      approximating the pairwise sequence comparison operations using hashing and also
      incorporates matching of fixed-length, gapless subsequences criterion to improve
      the quality of sequence comparisons. We use LSH-based similarity function to
      cluster similar sequences and make individual groups, called operational
      taxonomic units (OTUs). We also compute different species diversity/richness
      metrics by utilizing OTU assignment results to further extend our analysis.
      CONCLUSION: The algorithm is evaluated on synthetic samples and eight targeted
      16S rRNA metagenome samples taken from seawater. We compare the performance of
      our algorithm with several competing diversity estimation algorithms. We show the
      benefits of our approach with respect to computational runtime and meaningful OTU
      assignments. We also demonstrate practical significance of the developed
      algorithm by comparing bacterial diversity and structure across different skin
      locations. WEBSITE: http://www.cs.gmu.edu/~mlbio/LSH-DIV.

PMID- 24565032
TI  - Novel method for visualizing water transport through phase-separated polymer
      films.
AB  - Drug release from oral pharmaceutical formulations can be modified by applying a
      polymeric coating film with controlled mass transport properties. Interaction of
      the coating film with water may crucially influence its composition and
      permeability to both water and drug. Understanding this interaction between film
      microstructure, wetting, and mass transport is important for the development of
      new coatings. We present a novel method for controlled wetting of polymer coating
      films in an environmental scanning electron microscope, providing direct visual
      information about the processes occurring as the film goes from dry to wet. Free
      films made of phase-separated blends of water-insoluble ethyl cellulose (EC) and
      water-soluble hydroxypropyl cellulose (HPC) were used as a model system, and the
      blend ratio was varied to study the effect on the water transport properties.
      Local variations in water transport through the EC/HPC films were directly
      observed, enabling the immediate analysis of the structure-mass transport
      relationships. The leaching of HPC could be studied by evaporating water from the
      films in situ. Significant differences were observed between films of varying
      composition. The method provides a valuable complement to the current approach of
      making distinct diffusion and microscopy experiments for studying the dynamic
      interaction of polymer films with water. 

PMID- 24565033
TI  - Takotsubo's cardiomyopathy in the preoperative period of an emergent abdominal
      surgical procedure.

PMID- 24565035
TI  - BiCluE - Exact and heuristic algorithms for weighted bi-cluster editing of
      biomedical data.
AB  - BACKGROUND: The explosion of biological data has dramatically reformed today's
      biology research. The biggest challenge to biologists and bioinformaticians is
      the integration and analysis of large quantity of data to provide meaningful
      insights. One major problem is the combined analysis of data from different
      types. Bi-cluster editing, as a special case of clustering, which partitions two
      different types of data simultaneously, might be used for several biomedical
      scenarios. However, the underlying algorithmic problem is NP-hard. RESULTS: Here
      we contribute with BiCluE, a software package designed to solve the weighted bi
      cluster editing problem. It implements (1) an exact algorithm based on fixed
      parameter tractability and (2) a polynomial-time greedy heuristics based on
      solving the hardest part, edge deletions, first. We evaluated its performance on
      artificial graphs. Afterwards we exemplarily applied our implementation on real
      world biomedical data, GWAS data in this case. BiCluE generally works on any kind
      of data types that can be modeled as (weighted or unweighted) bipartite graphs.
      CONCLUSIONS: To our knowledge, this is the first software package solving the
      weighted bi-cluster editing problem. BiCluE as well as the supplementary results
      are available online at http://biclue.mpi-inf.mpg.de.

PMID- 24565034
TI  - Identification of mutated core cancer modules by integrating somatic mutation,
      copy number variation, and gene expression data.
AB  - MOTIVATION: Understanding the molecular mechanisms underlying cancer is an
      important step for the effective diagnosis and treatment of cancer patients. With
      the huge volume of data from the large-scale cancer genomics projects, an open
      challenge is to distinguish driver mutations, pathways, and gene sets (or core
      modules) that contribute to cancer formation and progression from random
      passengers which accumulate in somatic cells but do not contribute to
      tumorigenesis. Due to mutational heterogeneity, current analyses are often
      restricted to known pathways and functional modules for enrichment of somatic
      mutations. Therefore, discovery of new pathways and functional modules is a
      pressing need. RESULTS: In this study, we propose a novel method to identify
      Mutated Core Modules in Cancer (iMCMC) without any prior information other than
      cancer genomic data from patients with tumors. This is a network-based approach
      in which three kinds of data are integrated: somatic mutations, copy number
      variations (CNVs), and gene expressions. Firstly, the first two datasets are
      merged to obtain a mutation matrix, based on which a weighted mutation network is
      constructed where the vertex weight corresponds to gene coverage and the edge
      weight corresponds to the mutual exclusivity between gene pairs. Similarly, a
      weighted expression network is generated from the expression matrix where the
      vertex and edge weights correspond to the influence of a gene mutation on other
      genes and the Pearson correlation of gene mutation-correlated expressions,
      respectively. Then an integrative network is obtained by further combining these
      two networks, and the most coherent subnetworks are identified by using an
      optimization model. Finally, we obtained the core modules for tumors by filtering
      with significance and exclusivity tests. We applied iMCMC to the Cancer Genome
      Atlas (TCGA) glioblastoma multiforme (GBM) and ovarian carcinoma data, and
      identified several mutated core modules, some of which are involved in known
      pathways. Most of the implicated genes are oncogenes or tumor suppressors
      previously reported to be related to carcinogenesis. As a comparison, we also
      performed iMCMC on two of the three kinds of data, i.e., the datasets combining
      somatic mutations with CNVs and secondly the datasets combining somatic mutations
      with gene expressions. The results indicate that gene expressions or CNVs indeed
      provide extra useful information to the original data for the identification of
      core modules in cancer. CONCLUSIONS: This study demonstrates the utility of our
      iMCMC by integrating multiple data sources to identify mutated core modules in
      cancer. In addition to presenting a generally applicable methodology, our
      findings provide several candidate pathways or core modules recurrently perturbed
      in GBM or ovarian carcinoma for further studies.

PMID- 24565036
TI  - Fat and epidermal cell suspension grafting: a new advanced one-step skin
      regeneration surgical technique.
AB  - BACKGROUND: Dystrophic skin scarring commonly occurs following skin cancer
      resections. In particular, the cosmetic outcome of skin graft reconstructions,
      following epidermoidal carcinoma removal, is generally poor due to wide marginal
      tumour excision, loss of subcutaneous tissues, and subsequent pigmented atrophic
      scarring of the graft coverage. Skin grafting sequelae need a three dimensional
      correction to restore either the epidermal layer or the dermal/subdermal volume
      and vascularization. METHODS: The surgeons combined CO2 laser ablation, subdermal
      lipofilling according to the Coleman's technique and epidermal cell suspension
      autografting to correct wide depressed and dyschromic facial scar. The Authors
      applied this new technique on three nasal skin cancer resected patients: two of
      them actually need a longer follow-up, the third patient, a 48 yr old caucasian
      male, presented a skin grafting scar due to sclerodermiform basal cell carcinoma
      removal. This case is reported discussing pre-intra and post-operative records up
      to a complete twelve months follow-up. RESULTS: Records at six and twelve months
      follow-up after surgery demonstrate a fully integrated skin graft and a good
      restoration of the treated area, presenting the same texture and pigmentation of
      the adjacent untreated skin. Optimal, stable three-dimensional skin cosmetic
      restoration was obtained in a single stage surgical procedure. CONCLUSION:
      Autologous non-cultured epidermal cell suspension transplantation on an epidermal
      laser ablated skin area, in combination with lipofilling subdermal
      reconstruction, appears to be an effective, simple and time-saving method to
      correct skin graft sequelae, in skin cancer patients. This new technique allows
      to restore a three-dimensional morphological structure of the treated area and to
      recover a natural appearance of the skin at the same time. The Authors believe
      that this technique can be safely used to treat any kind of dystrophic scarring.

PMID- 24565037
TI  - Length of residence, age and patterns of medicinal plant knowledge and use among
      women in the urban Amazon.
AB  - BACKGROUND: This paper explores patterns of women's medicinal plant knowledge and
      use in an urban area of the Brazilian Amazon. Specifically, this paper examines
      the relationship between a woman's age and her use and knowledge of medicinal
      plants. It also examines whether length of residence in three different areas of
      the Amazon is correlated with a woman's use and knowledge of medicinal plants.
      Two of the areas where respondents may have resided, the jungle/seringal and
      farms/colonias, are classified as rural. The third area (which all of the
      respondents resided in) was urban. METHODS: This paper utilizes survey data
      collected in Rio Branco, Brazil. Researchers administered the survey to 153
      households in the community of Bairro da Luz (a pseudonym). The survey collected
      data on phytotherapeutic knowledge, general phytotherapeutic practice, recent
      phytotherapeutic practice and demographic information on age and length of
      residence in the seringal, on a colonia, and in a city. Bivariate correlation
      coefficients were calculated to assess the inter-relationships among the key
      variables. Three dependent variables, two measuring general phytotherapeutic
      practice and one measuring phytotherapeutic knowledge were regressed on the
      demographic factors. RESULTS: The results demonstrate a relationship between a
      woman's age and medicinal plant use, but not between age and plant knowledge.
      Additionally, length of residence in an urban area and on a colonia/farm are not
      related to medicinal plant knowledge or use. However, length of residence in the
      seringal/jungle is positively correlated with both medicinal plant knowledge and
      use. CONCLUSIONS: The results reveal a vibrant tradition of medicinal plant use
      in Bairro da Luz. They also indicate that when it comes to place of residence and
      phytotherapy the meaningful distinction is not rural versus urban, it is seringal
      versus other locations. Finally, the results suggest that phytotherapeutic
      knowledge and use should be measured separately since one may not be an accurate
      proxy for the other.

PMID- 24565038
TI  - Novel in vitro respiratory models to study lung development, physiology,
      pathology and toxicology.
AB  - Detailed studies of lung pathology in patients during the course of development
      of acute lung injury or respiratory distress are limited, and in the past
      information related to lung-specific responses has been derived from the study of
      lungs from patients who died at autopsy or from animal models. Development of
      good in vitro human tissue models would help to bridge the gap in our current
      knowledge of lung responses and provide a better understanding of lung
      development, physiology and pathology. In vitro models of simple one-cell or two
      cell culture systems as well as complex multicellular lung analogs that reproduce
      defined components of specific human lung responses have already been realized. A
      benefit of current in vitro lung models is that hypotheses generated from review
      of data from human or animal disease studies can be tested directly in engineered
      human tissue models. Results of studies done using simple in vitro lung systems
      or more complex three-dimensional models have already been used to examine cell
      based responses, physiologic functions, pathologic changes and even drug toxicity
      or drug responses. In the future we will create models with specific genetic
      profiles to test the importance of single gene products or pathways of
      significance. Recent development of microfluidics-based models that support high
      throughput screening will allow early-stage toxicity testing in human systems and
      faster development of new and innovative medical products. Model design in the
      future will also allow for evaluation of multiple organ systems at once,
      providing a more holistic or whole-body approach to understanding human
      physiology and responses. 

PMID- 24565039
TI  - Testosterone is associated with self-employment among Australian men.
AB  - Testosterone has pronounced effects on men's physiological development and
      smaller, more nuanced, impacts on their economic behavior. In this study of 1199
      Australian adult males, we investigate the relationship between the self-employed
      and their serum testosterone levels. Because prior studies have identified that
      testosterone is a hormone that is responsive to external factors (e.g.
      competition, risk-taking), we explicitly control for omitted variable bias and
      reverse causality by using an instrumental variable approach. We use insulin as
      our primary instrument to account for endogeneity between testosterone and self
      employment. This is because prior research has identified a relationship between
      insulin and testosterone but not between insulin and self-employment. Our results
      show that there is a positive association between total testosterone and self
      employment. Robustness checks using bioavailable testosterone and another similar
      instrument (daily alcohol consumption) confirm this positive finding. 

PMID- 24565041
TI  - Estimating loop length from CryoEM images at medium resolutions.
AB  - BACKGROUND: De novo protein modeling approaches utilize 3-dimensional (3D) images
      derived from electron cryomicroscopy (CryoEM) experiments. The skeleton
      connecting two secondary structures such as alpha-helices represent the loop in
      the 3D image. The accuracy of the skeleton and of the detected secondary
      structures are critical in De novo modeling. It is important to measure the
      length along the skeleton accurately since the length can be used as a constraint
      in modeling the protein. RESULTS: We have developed a novel computational
      geometric approach to derive a simplified curve in order to estimate the loop
      length along the skeleton. The method was tested using fifty simulated density
      images of helix-loop-helix segments of atomic structures and eighteen
      experimentally derived density data from Electron Microscopy Data Bank (EMDB).
      The test using simulated density maps shows that it is possible to estimate
      within 0.5 A of the expected length for 48 of the 50 cases. The experiments,
      involving eighteen experimentally derived CryoEM images, show that twelve cases
      have error within 2 A. CONCLUSIONS: The tests using both simulated and
      experimentally derived images show that it is possible for our proposed method to
      estimate the loop length along the skeleton if the secondary structure elements,
      such as alpha-helices, can be detected accurately, and there is a continuous
      skeleton linking the alpha-helices.

PMID- 24565040
TI  - Development and characterization of mouse monoclonal antibodies reactive with
      chicken TL1A.
AB  - Tumor necrosis factor-like ligand 1A (TL1A) is a type II transmembrane protein
      predominantly expressed by endothelial cells that promotes the expansion of
      activated T cells and regulatory T cells, modulates inflammation, and regulates
      the production of a wide variety of T cell cytokines. However, there have not
      been any mAbs which specifically detect chTL1A and define its biochemical and
      immunological properties. So in this study, two mouse monoclonal antibodies
      (mAbs) which specifically detect chicken TL1A (chTL1A) were developed and
      characterized. Both mAbs identified a 32 kDa Escherichia coli-derived, poly
      histidine-tagged fusion protein by Western blot analysis. The mAbs identified
      TL1A-secreting cells in the chicken thymus, cecal tonsil, and bursa of Fabricius
      by immunocytochemistry, and were used to measure serum TL1A levels in normal and
      necrotic enteritis (NE)-afflicted chickens by antigen capture ELISA. These mAbs
      inhibited chTL1A-induced spleen lymphocyte proliferation, nitric oxide production
      by chicken macrophage cells (HD11), and blocked the cytotoxic effect of chTL1A
      against lymphoblastoid chicken B tumor cells (LSCC-RP9). These new mAbs that
      detect chTL1A will be important immune reagents for basic and applied research in
      poultry immunology.

PMID- 24565042
TI  - An automatic segmentation and classification framework for anti-nuclear antibody
      images.
AB  - Autoimmune disease is a disorder of immune system due to the over-reaction of
      lymphocytes against one's own body tissues. Anti-Nuclear Antibody (ANA) is an
      autoantibody produced by the immune system directed against the self body tissues
      or cells, which plays an important role in the diagnosis of autoimmune diseases.
      Indirect ImmunoFluorescence (IIF) method with HEp-2 cells provides the major
      screening method to detect ANA for the diagnosis of autoimmune diseases.
      Fluorescence patterns at present are usually examined laboriously by experienced
      physicians through manually inspecting the slides with the help of a microscope,
      which usually suffers from inter-observer variability that limits its
      reproducibility. Previous researches only provided simple segmentation methods
      and criterions for cell segmentation and recognition, but a fully automatic
      framework for the segmentation and recognition of HEp-2 cells had never been
      reported before. This study proposes a method based on the watershed algorithm to
      automatically detect the HEp-2 cells with different patterns. The experimental
      results show that the segmentation performance of the proposed method is
      satisfactory when evaluated with percent volume overlap (PVO: 89%). The
      classification performance using a SVM classifier designed based on the features
      calculated from the segmented cells achieves an average accuracy of 96.90%, which
      outperforms other methods presented in previous studies. The proposed method can
      be used to develop a computer-aided system to assist the physicians in the
      diagnosis of auto-immune diseases. 

PMID- 24565043
TI  - Pitfalls in computer housekeeping by doctors and nurses in KwaZulu-Natal: no
      malicious intent.
AB  - INTRODUCTION: Information and communication technologies are becoming an integral
      part of medical practice, research and administration and their use will grow as
      telemedicine and electronic medical record use become part of routine practice.
      Security in maintaining patient data is important and there is a statuary
      obligation to do so, but few health professionals have been trained on how to
      achieve this. There is no information on the use of computers and email by
      doctors and nurses in South Africa in the workplace and at home, and whether
      their current computer practices meets legal and ethical requirements. The aims
      of this study were to determine the use of computers by healthcare practitioners
      in the workplace and home; the use and approach to data storage, encryption and
      security of patient data and patient email; and the use of informed consent to
      transmit data by email. METHODS: A self-administered questionnaire was
      administered to 400 health care providers from the state and private health care
      sectors. The questionnaire covered computer use in the workplace and at home,
      sharing of computers, data encryption and storage, email use, encryption of
      emails and storage, and the use of informed consent for email communication.
      RESULTS: 193 doctors and 207 nurses in the private and public sectors completed
      the questionnaire. Forty (10%) of participants do not use a computer. A third of
      health professionals were the only users of computers at work or at home. One
      hundred and ninety-eight respondents (55%) did not know if the data on the
      computers were encrypted, 132 (36.7%) knew that the data were not encrypted and
      30 (8.3%) individuals knew that the data on the computers they were using were
      encrypted. Few doctors, 58 (16%), received emails from patients, with doctors
      more likely to receive emails from patients than nurses (p = 0.0025). Thirty-one
      percent of individuals did not respond to the emails. Emails were saved by 40
      (69%) recipients but only 5 (12.5%) doctors encrypted the messages, 19 (47.5%)
      individuals knowingly did not encrypt and 16 (40.0%) did not know if they
      encrypted the data. While 20% of health professionals have emailed patient data,
      but only 41.7% gained consent to do so. CONCLUSIONS: Most health professionals as
      sampled in South Africa are not compliant with the National Health Act or the
      Electronic Communications Transactions Act of South Africa or guidelines from
      regulatory bodies when managing patient data on computers. Many appear ignorant
      or lack the ability to comply with simple data security procedures.

PMID- 24565044
TI  - Staphylococcus delphini and methicillin-resistant S. pseudintermedius in horses,
      Canada.

PMID- 24565045
TI  - Israeli nurse practice environment characteristics, retention, and job
      satisfaction.
AB  - BACKGROUND: There is an international nursing shortage. Improving the practice
      environment has been shown to be a successful strategy against this phenomenon,
      as the practice environment is associated with retention and job satisfaction.
      The Israeli nurse practice environment has not been measured. The purpose of this
      study was to measure practice environment characteristics, retention and job
      satisfaction and to evaluate the association between these variables. METHODS: A
      demographic questionnaire, the Practice Environment Scale, and a Job Satisfaction
      Questionnaire were administered to Israeli acute and intensive care nurses
      working in 7 hospitals across the country. Retention was measured by intent to
      leave the organization and work experience. A convenience sample of registered
      nurses was obtained using a bi-phasic, stratified, cluster design. Data were
      collected based on the preferences of each unit, either distribution during
      various shifts or at staff meetings; or via staff mailboxes. Descriptive
      statistics were used to describe the sample and results of the questionnaires.
      Pearson Product Moment Correlations were used to determine significant
      associations among the variables. A multiple regression model was designed where
      the criterion variable was the practice environment. Analyses of variance
      determined differences between groups on nurse practice environment
      characteristics. RESULTS: 610 nurses reported moderate levels of practice
      environment characteristics, where the lowest scoring characteristic was
      'appropriate staffing and resources'. Approximately 9% of the sample reported
      their intention to leave and the level of job satisfaction was high. A
      statistically significant, negative, weak correlation was found between intention
      to leave and practice environment characteristics, with a moderate correlation
      between job satisfaction and practice environment characteristics. 'Appropriate
      staffing and resources' was the only characteristic found to be statistically
      different based on hospital size and geographic region. CONCLUSIONS: This study
      supports the international nature of the vicious cycle that includes a poor
      quality practice environment, decreased job satisfaction and low nurse retention.
      Despite the extreme nursing shortage in Israel, perceptions of the practice
      environment were similar to other countries. Policy makers and hospital managers
      should address the practice environment, in order to improve job satisfaction and
      increase retention.

PMID- 24565046
TI  - Comparison on extreme pathways reveals nature of different biological processes.
AB  - BACKGROUND: Constraint-based reconstruction and analysis (COBRA) is used for
      modeling genome-scale metabolic networks (MNs). In a COBRA model, extreme
      pathways (ExPas) are the edges of its conical solution space, which is formed by
      all viable steady-state flux distributions. ExPa analysis has been successfully
      applied to MNs to reveal their phenotypic capabilities and properties. Recently,
      the COBRA framework has been extended to transcriptional regulatory networks
      (TRNs) and transcriptional and translational networks (TTNs), so efforts are
      needed to determine whether ExPa analysis is also effective on these two types of
      networks. RESULTS: In this paper, the ExPas resulting from the COBRA models of
      E.coli's MN, TRN and TTN were horizontally compared from 5 aspects: (1) Total
      number and the ratio of their amount to reaction amount; (2) Length distribution;
      (3) Reaction participation; (4) Correlated reaction sets (CoSets); (5)
      interconnectivity degree. Significant discrepancies in above properties were
      observed during the comparison, which reveals the biological natures of different
      biological processes. Besides, by demonstrating the application of ExPa analysis
      on E.coli, we provide a practical guidance of an improved approach to compute
      ExPas on COBRA models of TRNs. CONCLUSIONS: ExPas of E.coli's MN, TRN and TTN
      have different properties, which are strongly connected with various biological
      natures of biochemical networks, such as topological structure, specificity and
      redundancy. Our study shows that ExPas are biologically meaningful on the newborn
      models and suggests the effectiveness of ExPa analysis on them.

PMID- 24565049
TI  - An effective and effecient peptide binding prediction approach for a broad set of
      HLA-DR molecules based on ordered weighted averaging of binding pocket profiles.
AB  - BACKGROUND: The immune system must detect a wide variety of microbial pathogens,
      such as viruses, bacteria, fungi and parasitic worms, to protect the host against
      disease. Antigenic peptides displayed by MHC II (class II Major
      Histocompatibility Complex) molecules is a pivotal process to activate CD4+ TH
      cells (Helper T cells). The activated TH cells can differentiate into effector
      cells which assist various cells in activating against pathogen invasion. Each
      MHC locus encodes a great number of allele variants. Yet this limited number of
      MHC molecules are required to display enormous number of antigenic peptides.
      Since the peptide binding measurements of MHC molecules by biochemical
      experiments are expensive, only a few of the MHC molecules have suffecient
      measured peptides. To perform accurate binding prediction for those MHC alleles
      without suffecient measured peptides, a number of computational algorithms were
      proposed in the last decades. RESULTS: Here, we propose a new MHC II binding
      prediction approach, OWA-PSSM, which is a significantly extended version of a
      well known method called TEPITOPE. The TEPITOPE method is able to perform
      prediction for only 50 MHC alleles, while OWA-PSSM is able to perform prediction
      for much more, up to 879 HLA-DR molecules. We evaluate the method on five
      benchmark datasets. The method is demonstrated to be the best one in identifying
      binding cores compared with several other popular state-of-the-art approaches.
      Meanwhile, the method performs comparably to the TEPITOPE and NetMHCIIpan2.0
      approaches in identifying HLA-DR epitopes and ligands, and it performs
      significantly better than TEPITOPEpan in the identification of HLA-DR ligands and
      MultiRTA in identifying HLA-DR T cell epitopes. CONCLUSIONS: The proposed
      approach OWA-PSSM is fast and robust in identifying ligands, epitopes and binding
      cores for up to 879 MHC II molecules.

PMID- 24565051
TI  - The life cycle of Sclerocollum saudii Al-Jahdali, 2010 (Acanthocephala:
      Palaeacanthocephala: Rhadinorhynchidae) in amphipod and fish hosts from the Red
      Sea.
AB  - The rhadinorhynchid Sclerocollum saudii Al-Jahdali, 2010 was found in the
      intestine of its type host, Siganus rivulatus Forsskal & Niebuhr, 1775, a siganid
      fish permanently resident in a lagoon within the mangrove swamps found on the
      Egyptian coast of the Gulf of Aqaba (between 28 degrees 7'N and 28 degrees 18'N).
      Larval forms of this acanthocephalan (acanthors, acanthellae and cystacanths)
      were only found in Megaluropus agilis Hoek, 1889 (Crustacea: Gammaridae), a
      benthic amphipod abundant on algae and seagrasses in the lagoon. So, this life
      cycle of S. saudii was elucidated under semi-natural conditions: embryonated eggs
      of S. saudii were directly ingested by the amphipod and hatched in its intestine;
      the released acanthor penetrated the intestinal epithelium in 12-18 h to reach
      the connective tissue serosa, where it remained for about 3 days, then penetrated
      the intestinal wall and remained attached to its outer surface for 4 days. It
      then detached and dropped free in the amphipod haemocoel and transformed into an
      oval acanthella, growing for 16 days to reach the cystacanth stage. The
      cystacanth at 46 days post-infection was infective to fish (excysted in its
      intestine as an active juvenile). Male and female juveniles reached maturity 17
      and 23 days post-infection. Recently copulated females first appeared 26 days
      post-infection and all females seemed to be copulated at 28 days post-infection;
      partially and fully gravid females first appeared 31 and 35 days post-infection.
      Mature males and fully gravid females started to die off naturally 31 and 43 days
      post-infection and were totally expelled from the fish intestine by 42 and 52
      days post-infection. The cycle was completed in 89 days and is similar to other
      known palaeacanthocephalan life cycles, but has its own characteristics.

PMID- 24565048
TI  - Identifying protein complexes based on density and modularity in protein-protein
      interaction network.
AB  - BACKGROUND: Identifying protein complexes is crucial to understanding principles
      of cellular organization and functional mechanisms. As many evidences have
      indicated that the subgraphs with high density or with high modularity in PPI
      network usually correspond to protein complexes, protein complexes detection
      methods based on PPI network focused on subgraph's density or its modularity in
      PPI network. However, dense subgraphs may have low modularity and subgraph with
      high modularity may have low density, which results that protein complexes may be
      subgraphs with low modularity or with low density in the PPI network. As the
      density-based methods are difficult to mine protein complexes with low density,
      and the modularity-based methods are difficult to mine protein complexes with low
      modularity, both two methods have limitation for identifying protein complexes
      with various density and modularity. RESULTS: To identify protein complexes with
      various density and modularity, including those have low density but high
      modularity and those have low modularity but high density, we define a novel
      subgraph's fitness, frho, as frho= (density)(rho*)(modularity)(1-rho), and
      propose a novel algorithm, named LF_PIN, to identify protein complexes by
      expanding seed edges to subgraphs with the local maximum fitness value.
      Experimental results of LF-PIN in S.cerevisiae show that compared with the
      results of fitness equal to density (rho = 1) or equal to modularity (rho = 0),
      the LF-PIN identifies known protein complexes more effectively when the fitness
      value is decided by both density and modularity (0<rho<1). Compared with the
      results of seven competing protein complex detection methods (CMC, Core
      Attachment, CPM, DPClus, HC-PIN, MCL, and NFC) in S.cerevisiae and E.coli, LF-PIN
      outperforms other seven methods in terms of matching with known complexes and
      functional enrichment. Moreover, LF-PIN has better performance in identifying
      protein complexes with low density or with low modularity. CONCLUSIONS: By
      considering both the density and the modularity, LF-PIN outperforms other protein
      complexes detection methods that only consider density or modularity, especially
      in identifying known protein complexes with low density or low modularity.

PMID- 24565050
TI  - Investigation of anti-cancer mechanisms by comparative analysis of naked mole rat
      and rat.
AB  - BACKGROUND: The naked mole rats (NMRs) are small-sized underground rodents with
      plenty of unusual traits. Their life expectancy can be up to thirty years, more
      than seven times longer than laboratory rat. Furthermore, they are resistant to
      both congenital and experimentally induced cancer genesis. These peculiar
      physiological and pathological characteristics allow them to become a suitable
      model for cancer and aging research. RESULTS: In this paper, we carried out a
      genome-wide comparative analysis of rat and NMR using the recently published
      genome sequence of NMR. First, we identified all the rat-NMR orthologous genes
      and specific genes within each of them. The expanded and contracted numbers of
      protein families in NMR were also analyzed when compared to rat. Seven cancer
      related protein families appeared to be significantly expanded, whereas several
      receptor families were found to be contracted in NMR. We then chose those rat
      genes that were inexistent in NMR and adopted KEGG pathway database to
      investigate the metabolic processes in which their proteins may be involved.
      These genes were significantly enriched in two rat cancer pathways, "Pathway in
      cancer" and "Bladder cancer". In the rat "Pathway in cancer", 9 out of 14 paths
      leading to evading apoptosis appeared to be affected in NMR. In addition, a
      significant number of other NMR-missing genes enriched in several cancer-related
      pathways have been known to be related to a variety of cancers, implying that
      many of them may be also related to tumorigenesis in mammals. Finally,
      investigation of sequence variations among orthologous proteins between rat and
      NMR revealed that significant fragment insertions/deletions within important
      functional domains were present in some NMR proteins, which might lead to
      expressional and/or functional changes of these genes in different species.
      CONCLUSIONS: Overall, this study provides insights into understanding the
      possible anti-cancer mechanisms of NMR as well as searching for new cancer
      related candidate genes.

PMID- 24565052
TI  - Metastable structures in Al thin films before the onset of corrosion pitting as
      observed using liquid cell transmission electron microscopy.
AB  - One of the fundamental challenges in understanding the early stages of corrosion
      pitting in metals protected with an oxide film is that there are relatively few
      techniques that can probe microstructure with sufficient resolution while
      maintaining a wet environment. Here, we demonstrate that microstructural changes
      in Al thin films caused by aqueous NaCl solutions of varying chloride
      concentrations can be directly observed using a liquid flow cell enclosed within
      a transmission electron microscope (TEM) holder. In the absence of chloride, Al
      thin films did not exhibit significant corrosion when immersed in de-ionized
      water for 2 days. However, introducing 0.01 M NaCl solutions led to extensive
      random formation of blisters over the sample surface, while 0.1 M NaCl solutions
      formed anomalous structures that were larger than the typical grain size.
      Immersion in 1.0 M NaCl solutions led to fractal corrosion consistent with
      previously reported studies of Al thin films using optical microscopy. These
      results show the potential of in situ liquid cell electron microscopy for probing
      the processes that take place before the onset of pitting and for correlating pit
      locations with the underlying microstructure of the material. 

PMID- 24565047
TI  - Good manufacturing practice-compliant isolation and culture of human umbilical
      cord blood-derived mesenchymal stem cells.
AB  - BACKGROUND: Mesenchymal stem cells (MSCs) are an attractive source of stem cells
      for clinical applications. These cells exhibit a multilineage differentiation
      potential and strong capacity for immune modulation. Thus, MSCs are widely used
      in cell therapy, tissue engineering, and immunotherapy. Because of important
      advantages, umbilical cord blood-derived MSCs (UCB-MSCs) have attracted interest
      for some time. However, the applications of UCB-MSCs are limited by the small
      number of recoverable UCB-MSCs and fetal bovine serum (FBS)-dependent expansion
      methods. Hence, this study aimed to establish a xenogenic and allogeneic
      supplement-free expansion protocol. METHODS: UCB was collected to prepare
      activated platelet-rich plasma (aPRP) and mononuclear cells (MNCs). aPRP was
      applied as a supplement in Iscove modified Dulbecco medium (IMDM) together with
      antibiotics. MNCs were cultured in complete IMDM with four concentrations of aPRP
      (2, 5, 7, or 10%) or 10% FBS as the control. The efficiency of the protocols was
      evaluated in terms of the number of adherent cells and their expansion, the
      percentage of successfully isolated cells in the primary culture, surface marker
      expression, and in vitro differentiation potential following expansion. RESULTS:
      The results showed that primary cultures with complete medium containing 10% aPRP
      exhibited the highest success, whereas expansion in complete medium containing 5%
      aPRP was suitable. UCB-MSCs isolated using this protocol maintained their
      immunophenotypes, multilineage differentiation potential, and did not form tumors
      when injected at a high dose into athymic nude mice. CONCLUSION: This technique
      provides a method to obtain UCB-MSCs compliant with good manufacturing practices
      for clinical application.

PMID- 24565053
TI  - PREAL: prediction of allergenic protein by maximum Relevance Minimum Redundancy
      (mRMR) feature selection.
AB  - BACKGROUND: Assessment of potential allergenicity of protein is necessary
      whenever transgenic proteins are introduced into the food chain. Bioinformatics
      approaches in allergen prediction have evolved appreciably in recent years to
      increase sophistication and performance. However, what are the critical features
      for protein's allergenicity have been not fully investigated yet. RESULTS: We
      presented a more comprehensive model in 128 features space for allergenic
      proteins prediction by integrating various properties of proteins, such as
      biochemical and physicochemical properties, sequential features and subcellular
      locations. The overall accuracy in the cross-validation reached 93.42% to 100%
      with our new method. Maximum Relevance Minimum Redundancy (mRMR) method and
      Incremental Feature Selection (IFS) procedure were applied to obtain which
      features are essential for allergenicity. Results of the performance comparisons
      showed the superior of our method to the existing methods used widely. More
      importantly, it was observed that the features of subcellular locations and amino
      acid composition played major roles in determining the allergenicity of proteins,
      particularly extracellular/cell surface and vacuole of the subcellular locations
      for wheat and soybean. To facilitate the allergen prediction, we implemented our
      computational method in a web application, which can be available at
      http://gmobl.sjtu.edu.cn/PREAL/index.php. CONCLUSIONS: Our new approach could
      improve the accuracy of allergen prediction. And the findings may provide novel
      insights for the mechanism of allergies.

PMID- 24565054
TI  - Traditional medicine applied by the Saraguro yachakkuna: a preliminary approach
      to the use of sacred and psychoactive plant species in the southern region of
      Ecuador.
AB  - BACKGROUND: During the colonial period, the indigenous saraguros maintained their
      traditions, knowledge, and practices to restore and preserve the health of their
      members. Unfortunately, many of their practices and medicinal resources have not
      been documented. In this study, we sought to document the traditional healers'
      (yachakkuna saraguros) knowledge about medicinal and psychoactive plants used in
      the mesas and in magical-religious rituals. The study was conducted under a
      technical and scientific cooperation agreement between the Universidad Tecnica
      Particular de Loja (UTPL), the Direccion Provincial de Salud de Loja (DPSL), and
      the Saraguro Healers Council (Consejo de Sanadores de Saraguro). METHODS: For the
      present study, the DPSL and Saraguro Healers Council selected the 10 yachakkuna
      most recognized for their knowledge and their use of sacred and psychoactive
      species. Ten interviews with the selected yachakkuna were conducted between 2010
      and 2011 to ascertain how the Saraguro traditional healing system is structured
      and to obtain a record of the sacred and medicinal plant species used to treat
      supernatural diseases and for psychoactive purposes. RESULTS: The present study
      describes the traditional health system in the Saraguro indigenous community
      located in southern Ecuador. It also describes the main empirical methods used to
      diagnose diseases: direct physical examination of the patient, observation of the
      patient's urine, documentation of the patient's pulse, limpia, palpation and
      visionary methods, including supernatural diseases (susto, vaho de agua, mal
      aire, mal hecho, shuka) and reports of the use of sacred and medicinal
      psychoactive plants, such as the San Pedro cactus (Echinopsis pachanoi), wandug
      (Brugmansia spp.), and tobacco (Nicotiana spp.). This study also describes the
      rituals (limpia, soplada) employed by the Saraguro yachakkuna to treat
      supernatural diseases. Finally, we report on the main plants used during limpia
      in the Saraguro community. CONCLUSION: The current traditional health system in
      the Saraguro community is the cultural expression of the Saraguros' presence as
      an Andean group in southern Ecuador: it represents their character as indigenous
      group, their ability to survive as a community despite strong external pressure,
      and the desire to maintain their ancient healing heritage.

PMID- 24565055
TI  - Hydrogen peroxide-independent production of alpha-alkenes by OleTJE P450 fatty
      acid decarboxylase.
AB  - BACKGROUND: Cytochrome P450 OleTJE from Jeotgalicoccus sp. ATCC 8456, a new
      member of the CYP152 peroxygenase family, was recently found to catalyze the
      unusual decarboxylation of long-chain fatty acids to form alpha-alkenes using
      H2O2 as the sole electron and oxygen donor. Because aliphatic alpha-alkenes are
      important chemicals that can be used as biofuels to replace fossil fuels, or for
      making lubricants, polymers and detergents, studies on OleTJE fatty acid
      decarboxylase are significant and may lead to commercial production of biogenic
      alpha-alkenes in the future, which are renewable and more environmentally
      friendly than petroleum-derived equivalents. RESULTS: We report the H2O2
      independent activity of OleTJE for the first time. In the presence of NADPH and
      O2, this P450 enzyme efficiently decarboxylates long-chain fatty acids (C12 to
      C20) in vitro when partnering with either the fused P450 reductase domain RhFRED
      from Rhodococcus sp. or the separate flavodoxin/flavodoxin reductase from
      Escherichia coli. In vivo, expression of OleTJE or OleTJE-RhFRED in different E.
      coli strains overproducing free fatty acids resulted in production of variant
      levels of multiple alpha-alkenes, with a highest total hydrocarbon titer of 97.6
      mg.l-1. CONCLUSIONS: The discovery of the H2O2-independent activity of OleTJE not
      only raises a number of fundamental questions on the monooxygenase-like mechanism
      of this peroxygenase, but also will direct the future metabolic engineering work
      toward improvement of O2/redox partner(s)/NADPH for overproduction of alpha
      alkenes by OleTJE.

PMID- 24565057
TI  - Kala-azar and post-kala-azar dermal leishmaniasis, Assam, India.

PMID- 24565056
TI  - CD8+T cell-specific induction of NKG2D receptor by doxorubicin plus interleukin
      12 and its contribution to CD8+T cell accumulation in tumors.
AB  - BACKGROUND: Increased infiltration of CD8+T cells into tumors has a positive
      impact on survival. Our previous study showed that doxorubicin (Dox) plus
      interleukin-12 (IL-12) boosted the accumulation of CD8+T cells in tumors and had
      a greater antitumor effect than did either agent alone. The purpose of this study
      was to determine the impact of NKG2D expression on CD8+T cell infiltration and
      antitumor efficacy. METHODS: Tumor-bearing mice were administered Dox, IL-12
      plasmid DNA, or both via intraperitoneal injection or intramuscular
      electroporation. The induction of NKG2D on CD8+T cells and other lymphocytes was
      analyzed via flow cytometry, and NKG2D-positive CD8+T cell-specific localization
      in tumors was determined by using immunofluorescence staining in various types of
      immune cell-depleted mice. RESULTS: The combination of Dox plus IL-12
      specifically increased expression of NKG2D in CD8+T cells but not in other types
      of immune cells, including NK cells, which naturally express NKG2D. This induced
      NKG2D expression in CD8+T cells was associated with increased accumulation of
      CD8+T cells in murine tumors. Administration of NKG2D-blocking antibody or CD8+T
      cell-depletion antibody abrogated the NKG2D+CD8+T cell detection in tumors,
      whereas administration of NK cell-depletion antibody had no effect. Increased
      NKG2D expression in CD8+T cells was associated with increased antitumor efficacy
      in vivo. CONCLUSION: We conclude that Dox plus IL-12 induces NKG2D in CD8+T cells
      in vivo and boosts NKG2D+CD8+T-dependent antitumor immune surveillance. This
      discovery reveals a novel mechanism for how chemoimmunotherapy synergistically
      promotes T cell-mediated antitumor immune surveillance.

PMID- 24565059
TI  - The genome of Clostridium difficile 5.3.
AB  - BACKGROUND: Clostridium difficile is the leading cause of infectious diarrhea in
      humans and responsible for large outbreaks of enteritis in neonatal pigs in both
      North America and Europe. Disease caused by C. difficile typically occurs during
      antibiotic therapy and its emergence over the past 40 years is linked with the
      widespread use of broad-spectrum antibiotics in both human and veterinary
      medicine. RESULTS: We sequenced the genome of Clostridium difficile 5.3 using the
      Illumina Nextera XT and MiSeq technologies. Assembly of the sequence data
      reconstructed a 4,009,318 bp genome in 27 scaffolds with an N50 of 786 kbp. The
      genome has extensive similarity to other sequenced C. difficile genomes, but also
      has several genes that are potentially related to virulence and pathogenicity
      that are not present in the reference C. difficile strain. CONCLUSION: Genome
      sequencing of human and animal isolates is needed to understand the molecular
      events driving the emergence of C. difficile as a gastrointestinal pathogen of
      humans and food animals and to better define its zoonotic potential.

PMID- 24565058
TI  - Two accurate sequence, structure, and phylogenetic template-based RNA alignment
      systems.
AB  - BACKGROUND: The analysis of RNA sequences, once a small niche field for a small
      collection of scientists whose primary emphasis was the structure and function of
      a few RNA molecules, has grown most significantly with the realizations that 1)
      RNA is implicated in many more functions within the cell, and 2) the analysis of
      ribosomal RNA sequences is revealing more about the microbial ecology within all
      biological and environmental systems. The accurate and rapid alignment of these
      RNA sequences is essential to decipher the maximum amount of information from
      this data. METHODS: Two computer systems that utilize the Gutell lab's RNA
      Comparative Analysis Database (rCAD) were developed to align sequences to an
      existing template alignment available at the Gutell lab's Comparative RNA Web
      (CRW) Site. Multiple dimensions of cross-indexed information are contained within
      the relational database--rCAD, including sequence alignments, the NCBI
      phylogenetic tree, and comparative secondary structure information for each
      aligned sequence. The first program, CRWAlign-1 creates a phylogenetic-based
      sequence profile for each column in the alignment. The second program, CRWAlign-2
      creates a profile based on phylogenetic, secondary structure, and sequence
      information. Both programs utilize their profiles to align new sequences into the
      template alignment. RESULTS: The accuracies of the two CRWAlign programs were
      compared with the best template-based rRNA alignment programs and the best de
      novo alignment programs. We have compared our programs with a total of eight
      alternative alignment methods on different sets of 16S rRNA alignments with
      sequence percent identities ranging from 50% to 100%. Both CRWAlign programs were
      superior to these other programs in accuracy and speed. CONCLUSIONS: Both
      CRWAlign programs can be used to align the very extensive amount of RNA
      sequencing that is generated due to the rapid next-generation sequencing
      technology. This latter technology is augmenting the new paradigm that RNA is
      intimately implicated in a significant number of functions within the cell. In
      addition, the use of bacterial 16S rRNA sequencing in the identification of the
      microbiome in many different environmental systems creates a need for rapid and
      highly accurate alignment of bacterial 16S rRNA sequences.

PMID- 24565060
TI  - Points mean prizes: priority points, preferential status and directed organ
      donation in Israel.
AB  - The introduction of Israel's new Organ Transplantation Act in 2010 has enabled
      the development of a unique priority point system aimed at motivating
      individual's to donate their organ. The priority point system rewards those who
      are willing to donate an organ with preferential status and an increased chance
      of receiving a donor organ, should they come to be in need of one. Preliminary
      evidence suggests it has considerable public support among Israelis, who appear
      willing to redress the challenge posed by those who are willing to accept an
      organ but not willing to donate. Since the Act's introduction Israel has
      witnessed record numbers signing donor cards and there has been a significant
      increase in the actual numbers of transplants.One aspect of the new Israeli
      system that has hitherto not much been considered is its tendency towards a
      communitarian model of organ donation and the implications this change in
      emphasis may have for the existing 'opt-in' model based upon autonomy and
      consent. Gil Siegel draws our attention to this aspect when he sets out his
      defence of a proposal he refers to as 'directed organ donation to other
      registered donors', which encourages community responsibility without affecting
      the established commitment to consent and individual freedom.This commentary
      provides a brief overview of the new Act and its priority point system. It also
      examines Siegel's proposal and considers the implications it may have for equity
      and justice, personal choice and dispositional authority. It is argued that
      although the proposal brings with it several inevitable hurdles for policy makers
      these are not insurmountable. Rather, its extraordinary potential to save life
      and avoid suffering should prompt urgent action at policy level. If such a scheme
      was successfully implemented in Israel it would represent a landmark change in
      organ donation and allocation policy, and set an example from which we all could
      learn. 

PMID- 24565061
TI  - A conservation and rigidity based method for detecting critical protein residues.
AB  - BACKGROUND: Certain amino acids in proteins play a critical role in determining
      their structural stability and function. Examples include flexible regions such
      as hinges which allow domain motion, and highly conserved residues on functional
      interfaces which allow interactions with other proteins. Detecting these regions
      can aid in the analysis and simulation of protein rigidity and conformational
      changes, and helps characterizing protein binding and docking. We present an
      analysis of critical residues in proteins using a combination of two
      complementary techniques. One method performs in-silico mutations and analyzes
      the protein's rigidity to infer the role of a point substitution to Glycine or
      Alanine. The other method uses evolutionary conservation to find functional
      interfaces in proteins. RESULTS: We applied the two methods to a dataset of
      proteins, including biomolecules with experimentally known critical residues as
      determined by the free energy of unfolding. Our results show that the combination
      of the two methods can detect the vast majority of critical residues in tested
      proteins. CONCLUSIONS: Our results show that the combination of the two methods
      has the potential to detect more information than each method separately. Future
      work will provide a confidence level for the criticalness of a residue to improve
      the accuracy of our method and eliminate false positives. Once the combined
      methods are integrated into one scoring function, it can be applied to other
      domains such as estimating functional interfaces.

PMID- 24565062
TI  - The involvement of melatonin in the clinical status of patients with fibromyalgia
      syndrome.
AB  - OBJECTIVES: The aim of this study was to evaluate the levels of 6
      sulphatoxymelatonin (6-SMT) in the urine of patients with fibromyalgia (FM) and
      correlate them with the score obtained by these patients in four clinical
      assessment instruments. METHODS: Fifty-eight women with primary FM and 39 healthy
      women matched for age and body mass index were included in the study sample. The
      levels of 6-SMT were evaluated in urine collected from 8 pm until 8 am the next
      day by the immunosorbent assay. For the clinical evaluation we used the
      Fibromyalgia Impact Questionnaire (FIQ); Pittsburg Sleep Quality Index (PSQI);
      Medical Outcomes Study 36-item Short-Form Health Survey (SF-36) and Satisfaction
      with Life Scale (SWLS). Data normality was assessed using the Kolmogorov-Smirnov
      test, the differences between groups by means of the Mann-Whitney test and
      correlation analysis by Spearman's correlation test. RESULTS: The levels of 6-SMT
      in the urine of patients with FM were significantly lower than those found in the
      urine of healthy controls. The score obtained by patients with FM was
      significantly different from the score achieved by the healthy controls in the
      four assessment tools. However, no significant correlation between urinary levels
      of 6-SMT and scores on assessment instruments was observed. CONCLUSIONS: The
      results of this study do not discard the involvement of melatonin in the
      pathophysiology of FM, but may suggest that changes in melatonin levels when
      associated with other neuroimmunoendocrine changes may impact directly and
      negatively on the manifestation of symptoms that make up the clinical picture of
      FM.

PMID- 24565063
TI  - HeLiVa platform: integrated heart-liver-vascular systems for drug testing in
      human health and disease.
AB  - Our project team is developing an integrated microphysiological platform with
      functionally connected vascular, liver and cardiac microtissues derived from a
      single line of human pluripotent stem cells. The platform enables functional
      representation of human physiology in conjunction with real-time biological
      readouts (via imaging and homologous reporters for all three cell phenotypes) and
      compatibility with high-throughput/high-content analysis. In this paper, we
      summarize progress made over the first year of the grant. 

PMID- 24565065
TI  - Paper patching of the tympanic membrane as a symptomatic treatment for patulous
      eustachian tube syndrome.
AB  - BACKGROUND: Application of one or several paper patches on the tympanic membrane
      can improve autophony and other symptoms in some patients with a patulous
      eustachian tube. METHOD: The charts of 21 patients treated for patulous
      eustachian tube syndrome between 2006 and 2011 were studied for subjective
      improvement of symptoms following the application of paper patches. RESULTS:
      Paper patching of the tympanic membrane provided symptomatic relief in 76.2 per
      cent of patients; relief was permanent in 50 per cent of these patients.
      CONCLUSION: Paper patching of the tympanic membrane is a simple and effective
      means of temporarily or permanently alleviating patulous eustachian tube syndrome
      symptoms. It is postulated that the patches decrease the admittance of low- to
      mid-frequency acoustic input at the tympanic membrane by increasing the stiffness
      of the tympanic membrane, thereby counteracting the middle-ear cushion effect
      caused by the open eustachian tube.

PMID- 24565064
TI  - Prioritizing protein complexes implicated in human diseases by network
      optimization.
AB  - BACKGROUND: The detection of associations between protein complexes and human
      inherited diseases is of great importance in understanding mechanisms of
      diseases. Dysfunctions of a protein complex are usually defined by its member
      disturbance and consequently result in certain diseases. Although individual
      disease proteins have been widely predicted, computational methods are still
      absent for systematically investigating disease-related protein complexes.
      RESULTS: We propose a method, MAXCOM, for the prioritization of candidate protein
      complexes. MAXCOM performs a maximum information flow algorithm to optimize
      relationships between a query disease and candidate protein complexes through a
      heterogeneous network that is constructed by combining protein-protein
      interactions and disease phenotypic similarities. Cross-validation experiments on
      539 protein complexes show that MAXCOM can rank 382 (70.87%) protein complexes at
      the top against protein complexes constructed at random. Permutation experiments
      further confirm that MAXCOM is robust to the network structure and parameters
      involved. We further analyze protein complexes ranked among top ten for breast
      cancer and demonstrate that the SWI/SNF complex is potentially associated with
      breast cancer. CONCLUSIONS: MAXCOM is an effective method for the discovery of
      disease-related protein complexes based on network optimization. The high
      performance and robustness of this approach can facilitate not only pathologic
      studies of diseases, but also the design of drugs targeting on multiple proteins.

PMID- 24565066
TI  - Caught in the act: endoscopic characterization of sessile serrated adenomas with
      dysplasia.

PMID- 24565067
TI  - Colonoscopy utilization and outcomes 2000 to 2011.
AB  - BACKGROUND: Understanding colonoscopy utilization and outcomes can help determine
      when the procedure is most effective. OBJECTIVE: To study trends in utilization
      and outcomes of colonoscopy in the United States from 2000 to 2011. DESIGN:
      Prospective collection of colonoscopy data. SETTING: A total of 84 adult diverse
      GI practices. PATIENTS: All adult patients receiving colonoscopy for any reason.
      INTERVENTION: Colonoscopy. MAIN OUTCOME MEASUREMENTS: Polyps >9 mm or suspected
      malignant tumor. RESULTS: We analyzed 1,372,838 reports. The most common reason
      for colonoscopy in patients aged <50 years is evaluation of symptoms such as
      irritable bowel syndrome (IBS) (28.7%) and bleeding or anemia (35.3%). In
      patients aged 50 to 74 years, colorectal cancer screening accounts for 42.9% of
      examinations. In patients aged >74 years, surveillance for cancer or polyps is
      the most common indication. The use of colonoscopy for average-risk screening
      increased nearly 3-fold during the study period. The prevalence of large polyps
      increases with age and is higher in men for every procedure indication. The
      prevalence of large polyps in patients with symptoms of IBS was lower than in
      those undergoing average-risk screening (odds ratio [OR] 0.85; 95% confidence
      interval [CI], 0.83-0.87). With increasing age, there was a shift from distal to
      proximal large polyps. The rate of proximal large polyps is higher in the black
      population compared with the white population (OR 1.19; 95% CI, 1.13-1.25).
      LIMITATIONS: In the absence of pathology data, use of surrogate as the main
      outcome. CONCLUSION: Colonoscopy utilization changed from 2000 to 2011, with an
      increase in primary screening. The proximal location of large polyps in the black
      population and with advancing age has implications for screening and
      surveillance.

PMID- 24565068
TI  - Increasing duodenal intraepithelial lymphocytosis found at upper endoscopy: time
      trends and associations.
AB  - BACKGROUND: Increased intraepithelial lymphocytosis (IEL) with preserved villous
      architecture is a common yet nonspecific finding on duodenal biopsies. OBJECTIVE:
      To study the change in frequency of isolated IEL on duodenal biopsy over time and
      determine whether previously reported disease associations have changed during
      that period. DESIGN: Retrospective study. SETTING: Single tertiary-care referral
      center. PATIENTS: Adults with a duodenal biopsy that showed normal villi and
      increased number of intraepithelial lymphocytes. INTERVENTION: Duodenal biopsy.
      Comprehensive electronic medical record search from January 1, 2000 through
      December 31, 2010. MAIN OUTCOME MEASUREMENTS: Demographic and clinical
      information. RESULTS: Of the 15,839 duodenal biopsies performed during the study
      period, 1105 (7.0%) had the histologic finding of interest. The odds of finding
      newly diagnosed celiac disease (CD) decreased by 0.9 on average during each year,
      whereas the odds of finding a non-celiac association increased by 1.12 times each
      year. Isolated increased IEL attributed to nonsteroidal anti-inflammatory drug
      (NSAID) use and small-intestine bacterial overgrowth (SIBO) increased by 1.06 and
      1.3 times, respectively, for each year on average. LIMITATIONS: Retrospective
      design, single center. CONCLUSION: During the years 2000 through 2010, there has
      been an increased frequency with which duodenal biopsies were noted to have
      isolated increased IEL. The odds of a diagnosis of CD accounting for this finding
      have been decreasing, whereas the odds of NSAID use and SIBO have been
      increasing. Although the finding of isolated increased IEL on duodenal biopsy
      warrants work-up for CD in all patients, further investigation for other possible
      causes, including NSAID use and SIBO, should be considered as well.

PMID- 24565069
TI  - Recurrent upper GI bleeding secondary to coil migration in a patient with known
      NSAID-induced peptic ulcer disease.

PMID- 24565070
TI  - Endoscopic placement of self-expandable metal stents for treatment of
      rectovaginal fistulas after colorectal resection for cancer.

PMID- 24565072
TI  - Effectiveness of a balloon catheter with a side hole for introducing a guidewire
      into an infected pancreatic pseudocyst.

PMID- 24565071
TI  - Positive correlation between endoscopist radiofrequency ablation volume and
      response rates in Barrett's esophagus.
AB  - BACKGROUND: Radiofrequency ablation (RFA) has become an accepted form of
      endoscopic treatment for Barrett's esophagus (BE), yet reported response rates
      are variable. There are no accepted quality measures for performing RFA, and
      provider-level characteristics may influence RFA outcomes. OBJECTIVE: To
      determine whether endoscopist RFA volume is associated with rates of complete
      remission of intestinal metaplasia (CRIM) after RFA in patients with BE. DESIGN:
      Retrospective analysis of longitudinal data. SETTING: Three tertiary-care medical
      centers. PATIENTS: Patients with BE treated with RFA. INTERVENTION RFA MAIN
      OUTCOME MEASUREMENTS: For each endoscopist, we recorded RFA volume, defined as
      the number of unique patients treated as well as corresponding CRIM rates. We
      calculated a Spearman correlation coefficient relating these 2 measures. RESULTS:
      We identified 417 patients with BE treated with RFA who had at least 1 post-RFA
      endoscopy with biopsies. A total of 73% of the cases had pretreatment histology
      of high-grade dysplasia or adenocarcinoma. The procedures were performed by 7
      endoscopists, who had a median RFA volume of 62 patients (range 20-188). The
      overall CRIM rate was 75.3% (provider range 62%-88%). The correlation between
      endoscopist RFA volume and CRIM rate was strong and significant (rho = 0.85; P =
      .014). In multivariable analysis, higher RFA volume was significantly associated
      with CRIM (P for trend .04). LIMITATIONS: Referral setting may limit
      generalizability. Limited number of endoscopists analyzed. CONCLUSION:
      Endoscopist RFA volume correlates with rates of successful BE eradication.
      Further studies are required to confirm these findings and to determine whether
      RFA volume is a valid predictor of treatment outcomes in BE.

PMID- 24565074
TI  - PPIRank - an advanced method for ranking protein-protein interations in TAP/MS
      data.
AB  - BACKGROUND: Tandem affinity purification coupled with mass-spectrometry (TAP/MS)
      analysis is a popular method for the identification of novel endogenous protein
      protein interactions (PPIs) in large-scale. Computational analysis of TAP/MS data
      is a critical step, particularly for high-throughput datasets, yet it remains
      challenging due to the noisy nature of TAP/MS data. RESULTS: We investigated
      several major TAP/MS data analysis methods for identifying PPIs, and developed an
      advanced method, which incorporates an improved statistical method to filter out
      false positives from the negative controls. Our method is named PPIRank that
      stands for PPI ranking in TAP/MS data. We compared PPIRank with several other
      existing methods in analyzing two pathway-specific TAP/MS PPI datasets from
      Drosophila. CONCLUSION: Experimental results show that PPIRank is more capable
      than other approaches in terms of identifying known interactions collected in the
      BioGRID PPI database. Specifically, PPIRank is able to capture more true
      interactions and simultaneously less false positives in both Insulin and Hippo
      pathways of Drosophila Melanogaster.

PMID- 24565073
TI  - Clinical outcomes of endoscopic submucosal dissection for superficial Barrett's
      adenocarcinoma.
AB  - BACKGROUND: Advances in diagnostic techniques have allowed early stage detection
      of superficial Barrett's adenocarcinoma (SBA) as well as resection by endoscopic
      submucosal dissection (ESD). Few reports exist, however, on the safety and
      efficacy of ESD for SBA. OBJECTIVE: To analyze outcomes of ESD for SBA in
      relation to clinicopathological features of the lesions. DESIGN: Retrospective
      study. SETTING: University hospital. PATIENTS: Twenty-three patients (21 men, 2
      women; mean age, 63 years) with 26 SBAs. INTERVENTION ESD MAIN OUTCOME
      MEASUREMENTS: We examined outcomes of ESD in relation to the clinicopathological
      features of SBAs. The main outcomes assessed were en bloc resection rate,
      operation time, adverse event rates, additional resection rate, and time between
      ESD and any recurrence. RESULTS: Twenty lesions (87%) derived from short-segment
      Barrett's esophagus, and 3 lesions (13%) derived from long-segment Barrett's
      esophagus. The majority of SBAs (54%) were located in the 0 to 3 o'clock
      circumferential quadrant. Median tumor size was 15 mm (range 5-60 mm).
      Macroscopic types were flat elevated (n = 13, 50%), depressed (n = 12, 46%), and
      protruded (n = 1, 4%). The SBAs appeared red (n = 23, 88%) or normally pale (n =
      3, 12%). Under magnifying narrow-band imaging, all SBAs showed an irregular
      mucosal pattern and an irregular vascular pattern. The endoscopic en bloc
      resection rate was 100% (26/26), and the pathological en bloc resection rate was
      85% (22/26). The median procedure time was 95 minutes (range, 30-210 minutes).
      Delayed bleeding occurred in 1 case, but there was no perforation. The SBAs were
      of the differentiated type (n = 25, 96%) or poorly differentiated type (n = 1,
      4%). The tumor had invaded the superficial muscularis mucosa (n = 3, 12%), lamina
      propria mucosa (n = 5, 19%, deep muscularis mucosa (n = 9, 34%), SM1 (n = 3,
      12%), and SM2 (n = 6, 23%). Additional surgical resection after ESD was performed
      in 9 cases, and there were no residual tumors, but 1 lymph node metastasis was
      found. There were no recurrent tumors; however, 1 metachronous adenocarcinoma was
      diagnosed 42 months after ESD. LIMITATIONS: Single-center, retrospective study.
      CONCLUSIONS: ESD appears to be a safe and effective treatment strategy for early
      stage SBA.

PMID- 24565075
TI  - Sirtuin 1 attenuates oxidative stress via upregulation of superoxide dismutase 2
      and catalase in astrocytes.
AB  - Sirtuin 1 (SIRT1) exerts a neuroprotective effect on various neurologic diseases.
      Here we investigated the protective functions of SIRT1 in astrocytes, which are
      the most abundant cells in the central nervous system. Upregulation of SIRT1
      suppressed the expression levels of pro-inflammatory cytokines and increased the
      expression levels of superoxide dismutase 2 and catalase. Inversely, inhibition
      of SIRT1 significantly increased the acetylation of forkhead box protein O4,
      decreased the expression levels of superoxide dismutase 2 and catalase, and
      increased the production of reactive oxygen species. Our data suggest that
      astrocytic SIRT1 may elicit neuroprotective effects through its anti-oxidative
      and anti-inflammatory functions. 

PMID- 24565076
TI  - Therapeutic potential of atorvastatin-modified dendritic cells in experimental
      autoimmune neuritis by decreased Th1/Th17 cytokines and up-regulated T regulatory
      cells and NKR-P1(+) cells.
AB  - Statins have pleiotropic effects which include anti-inflammatory and
      immunomodulatory effects. In the present study, dendritic cells treated with
      atorvastatin (statin-DCs) could be induced into tolerogenic DCs. Administration
      of these tolerogenic DCs ameliorated clinical symptoms in experimental autoimmune
      neuritis (EAN), which was associated with reduced number of inflammatory cells in
      sciatic nerves, inhibited CD4(+) T cells proliferation, down-regulated expression
      of co-stimulatory molecules (CD80 and CD86) and MHC class II, decreased levels of
      IFN-gamma, TNF-alpha and IL-17A, increased number of NKR-P1(+) cells (including
      NK and NKT cells), up-regulated number of Treg cells in lymph node MNC as well as
      increased Foxp3 expression in the thymus. These data indicated that statin-DCs
      could develop as a new therapeutic strategy to GBS in the future. 

PMID- 24565077
TI  - Communicating information about "what not to do" to consumers.
AB  - BACKGROUND: Americans devote more resources to health care than any other
      developed country, and yet they have worse health outcomes and less access. This
      creates a perfect set of opportunities for Consumer Reports, a nonprofit consumer
      advocacy and multimedia organization known for its focus on individual consumers
      in markets where significant amounts of misinformation is in play. Consumer
      Reports uses comparisons/ratings based on the best available data to "level" the
      market playing field. While our early efforts to inform consumers of overuse and
      underuse in health care were successful, we sensed there were opportunities to
      have greater impact. Over a 5-year period, with the help of many partners,
      Consumer Reports learned more about how to communicate "what not to do" to
      consumers, ultimately enhancing the effectiveness of this difficult message.
      ANALYSIS: Consumer Reports began an in-depth examination of the overuse of health
      services in 2010 with an exploratory review of the cognitive psychology
      literature. Lessons learned from this review were used in the presentation of
      subsequent ratings of heart disease and cancer screening tests. Surveys showed
      surprising gaps in the prevention/screening knowledge of healthy, low-risk
      Consumer Reports subscribers aged 40 to 60 years. Of these subscribers, 44%
      reported engaging in heart screening tests that received the lowest ratings from
      the U.S. Preventive Services Task Force and from Consumer Reports. At the same
      time professional societies and the ABIM (American Board of Internal Medicine)
      Foundation created Choosing Wisely(r), a campaign focused on identifying lists of
      health tests and treatments not to do. Consumer Reports joined the Choosing
      Wisely campaign as the consumer "translator" and organizer of a network of
      consumer organizations with access to tens of millions of consumers. Over the
      past year, Consumer Reports has conducted multiple qualitative evaluations of
      content related to overuse of health services. Ratings of cancer screening tests
      were released in 2013 in an article readers reported as one of the most heavily
      read articles in the magazine's recent history. CONCLUSIONS: Telling consumers
      that more is not better is not a popular or easy message to deliver. The message
      is most likely to be "sticky" but is best received if it comes from trusted
      sources (e.g., physicians), focuses on safety when justified, is communicated in
      plain language, and uses both mass media and individual consumer approaches.
      Changing the culture of health care in an era of health reform is an essential
      part of the transformation needed if we are to allocate finite resources fairly
      in hopefully fair markets while assuring that better quality products and
      services at lower prices dominate.

PMID- 24565078
TI  - Quantitative three-dimensional cardiovascular magnetic resonance myocardial
      perfusion imaging in systole and diastole.
AB  - BACKGROUND: Two-dimensional (2D) perfusion cardiovascular magnetic resonance
      (CMR) remains limited by a lack of complete myocardial coverage. Three
      dimensional (3D) perfusion CMR addresses this limitation and has recently been
      shown to be clinically feasible. However, the feasibility and potential clinical
      utility of quantitative 3D perfusion measurements, as already shown with 2D
      perfusion CMR and positron emission tomography, has yet to be evaluated. The
      influence of systolic or diastolic acquisition on myocardial blood flow (MBF)
      estimates, diagnostic accuracy and image quality is also unknown for 3D-perfusion
      CMR. The purpose of this study was to establish the feasibility of quantitative
      3D-perfusion CMR for the detection of coronary artery disease (CAD) and to
      compare systolic and diastolic estimates of MBF. METHODS: Thirty-five patients
      underwent 3D-perfusion CMR with data acquired at both end-systole and mid
      diastole. MBF and myocardial perfusion reserve (MPR) were estimated on a per
      patient and per territory basis by Fermi-constrained deconvolution. Significant
      CAD was defined as stenosis >=70% on quantitative coronary angiography. RESULTS:
      Twenty patients had significant CAD (involving 38 out of 105 territories). Stress
      MBF and MPR had a high diagnostic accuracy for the detection of CAD in both
      systole (area under curve [AUC]: 0.95 and 0.92, respectively) and diastole (AUC:
      0.95 and 0.94). There were no significant differences in the AUCs between systole
      and diastole (p values >0.05). At stress, diastolic MBF estimates were
      significantly greater than systolic estimates (no CAD: 3.21 +/- 0.50 vs. 2.75 +/-
      0.42 ml/g/min, p < 0.0001; CAD: 2.13 +/- 0.45 vs. 1.98 +/- 0.41 ml/g/min, p <
      0.0001); but at rest, there were no significant differences (p values >0.05).
      Image quality was higher in systole than diastole (median score 3 vs. 2, p =
      0.002). CONCLUSIONS: Quantitative 3D-perfusion CMR is feasible. Estimates of MBF
      are significantly different for systole and diastole at stress but diagnostic
      accuracy to detect CAD is high for both cardiac phases. Better image quality
      suggests that systolic data acquisition may be preferable.

PMID- 24565079
TI  - Metabolomic profiling of schizophrenia patients at risk for metabolic syndrome.
AB  - Second-generation antipsychotics (SGAs) are commonly used to treat schizophrenia.
      However, SGAs cause metabolic disturbances that can manifest as metabolic
      syndrome (MetS) in a subset of patients. The causes for these metabolic
      disturbances remain unclear. We performed a comprehensive metabolomic profiling
      of 60 schizophrenia patients undergoing treatment with SGAs that puts them at
      high (clozapine, olanzapine), medium (quetiapine, risperidone), or low
      (ziprasidone, aripiprazole) risk for developing MetS, compared to a cohort of 20
      healthy controls. Multiplex immunoassays were used to measure 13 metabolic
      hormones and adipokines in plasma. Mass spectrometry was used to determine levels
      of lipids and polar metabolites in 29 patients and 10 controls. We found that
      levels of insulin and tumor necrosis factor alpha (TNF-alpha) were significantly
      higher (p < 0.005) in patients at medium and high risk for MetS, compared to
      controls. These molecules are known to be increased in individuals with high body
      fat content and obesity. On the other hand, adiponectin, a molecule responsible
      for control of food intake and body weight, was significantly decreased in
      patients at medium and high risk for MetS (p < 0.005). Further, levels of
      dyacylglycerides (DG), tryacylglycerides (TG) and cholestenone were increased,
      whereas alpha-Ketoglutarate and malate, important mediators of the tricarboxylic
      acid (TCA) cycle, were significantly decreased in patients compared to controls.
      Our studies suggest that high- and medium-risk SGAs are associated with
      disruption of energy metabolism pathways. These findings may shed light on the
      molecular underpinnings of antipsychotic-induced MetS and aid in design of novel
      therapeutic approaches to reduce the side effects associated with these drugs. 

PMID- 24565081
TI  - A categorical network approach for discovering differentially expressed
      regulations in cancer.
AB  - BACKGROUND: The problem of efficient utilization of genome-wide expression
      profiles for identification and prediction of complex disease conditions is both
      important and challenging. Polygenic pathologies such as most types of cancer
      involve disregulation of many interacting genes which has prompted search for
      suitable statistical models for their representation. By accounting for changes
      in gene regulations between comparable conditions, graphical statistical models
      are expected to improve prediction precision. METHODS: In comparison problems
      with two or more experimental conditions, we represent the classes by categorical
      Bayesian networks that share one and the same graph structure but have class
      specific probability parameters. The graph structure is learned by a score-based
      procedure that maximizes the difference between class probabilities using a
      suitable measure of divergence. The proposed framework includes an indirect model
      selection by adhering to a principle of optimal class separation and identifies
      interactions presenting significant difference between the compared conditions.
      RESULTS: We evaluate the performance of the new model against some benchmark
      algorithms such as support vector machine, penalized linear regression and linear
      Gaussian networks. The classifiers are compared by prediction accuracy across 15
      different data sets from breast, lung, gastric and renal cancer studies. In
      addition to the demonstrated strong performance against the competitors, the
      proposed method is able to identify disease specific changes in gene regulations
      which are inaccessible by other approaches. The latter is illustrated by
      analyzing some gene interactions differentiating adenocarcinoma and squamous cell
      lung cancers.

PMID- 24565080
TI  - An international collaborative study to determine the prevalence of contagious
      caprine pleuropneumonia by monoclonal antibody-based cELISA.
AB  - BACKGROUND: Few serological tests are available for detecting antibodies against
      Mycoplasma capricolum subsp. capripneumoniae, the causal agent of contagious
      caprine pleuropneumonia (CCPP). The complement fixation test, the test prescribed
      for international trade purposes, uses a crude antigen that cross-reacts with all
      the other mycoplasma species of the "mycoides cluster" frequently infecting goat
      herds. The lack of a more specific test has been a real obstacle to the
      evaluation of the prevalence and economic impact of CCPP worldwide. A new
      competitive ELISA kit for CCPP, based on a previous blocking ELISA, was formatted
      at CIRAD and used to evaluate the prevalence of CCPP in some regions of Kenya,
      Ethiopia, Mauritius, Tajikistan and Pakistan in an international collaborative
      study. RESULTS: The strict specificity of the test was confirmed in CCPP-free
      goat herds exposed to other mycoplasma species of the "mycoides cluster".
      Prevalence studies were performed across the enzootic range of the disease in
      Africa and Asia. Seroprevalence was estimated at 14.6% in the Afar region of
      Ethiopia, whereas all the herds presented for CCPP vaccination in Kenya tested
      positive (individual seroprevalence varied from 6 to 90% within each herd). In
      Mauritius, where CCPP emerged in 2009, nine of 62 herds tested positive. In
      Central Asia, where the disease was confirmed only recently, no positive animals
      were detected in the Wakhan District of Afghanistan or across the border in
      neighboring areas of Tajikistan, whereas seroprevalence varied between 2.7% and
      44.2% in the other districts investigated and in northern Pakistan. The test was
      also used to monitor seroconversion in vaccinated animals. CONCLUSIONS: This
      newly formatted CCPP cELISA kit has retained the high specificity of the original
      kit. It can therefore be used to evaluate the prevalence of CCPP in countries or
      regions without vaccination programs. It could also be used to monitor the
      efficacy of vaccination campaigns as high-quality vaccines induce high rates of
      seroconversion.

PMID- 24565083
TI  - Guided waves dispersion equations for orthotropic multilayered pipes solved using
      standard finite elements code.
AB  - The dispersion curves for hollow multilayered cylinders are prerequisites in any
      practical guided waves application on such structures. The equations for
      homogeneous isotropic materials have been established more than 120 years ago.
      The difficulties in finding numerical solutions to analytic expressions remain
      considerable, especially if the materials are orthotropic visco-elastic as in the
      composites used for pipes in the last decades. Among other numerical techniques,
      the semi-analytical finite elements method has proven its capability of solving
      this problem. Two possibilities exist to model a finite elements eigenvalue
      problem: a two-dimensional cross-section model of the pipe or a radial segment
      model, intersecting the layers between the inner and the outer radius of the
      pipe. The last possibility is here adopted and distinct differential problems are
      deduced for longitudinal L(0,n), torsional T(0,n) and flexural F(m,n) modes.
      Eigenvalue problems are deduced for the three modes classes, offering explicit
      forms of each coefficient for the matrices used in an available general purpose
      finite elements code. Comparisons with existing solutions for pipes filled with
      non-linear viscoelastic fluid or visco-elastic coatings as well as for a fully
      orthotropic hollow cylinder are all proving the reliability and ease of use of
      this method.

PMID- 24565082
TI  - Identification of key regulators in glycogen utilization in E. coli based on the
      simulations from a hybrid functional Petri net model.
AB  - BACKGROUND: Glycogen and glucose are two sugar sources available during the lag
      phase of E. coli, but the mechanism that regulates their utilization is still
      unclear. METHODS: Attempting to unveil the relationship between glucose and
      glycogen, we propose an integrated hybrid functional Petri net (HFPN) model
      including glycolysis, PTS, glycogen metabolic pathway, and their internal
      regulatory systems. RESULTS AND CONCLUSIONS: By comparing known biological
      results to this model, basic necessary regulatory mechanism for utilizing glucose
      and glycogen were identified as a feedback circuit in which HPr and EIIAGlc play
      key roles. Based on this regulatory HFPN model, we discuss the process of
      glycogen utilization in E. coli in the context of a systematic understanding of
      carbohydrate metabolism.

PMID- 24565084
TI  - Septic arthritis caused by Streptococcus suis serotype 5 in pig farmer.

PMID- 24565086
TI  - Respiratory rate as a predictor of weaning failure from mechanical ventilation.
AB  - BACKGROUND AND OBJECTIVE: There is not an ideal predictor of weaning from
      mechanical ventilation (MV). In a large meta-analysis, despite methodological
      limitations, respiratory rate (RR) was considered a promising predictor. The aim
      of this study was to evaluate RR as a predictor of weaning failure from MV.
      METHODS: We prospectively evaluated 166 patients scheduled for weaning from MV.
      RR and other essential criteria for weaning were evaluated at an early stage of
      screening. Patients who met the essential screening criteria for weaning
      underwent spontaneous breathing trial. RR was compared with the following
      outcomes: weaning success/failure or extubation failure. RESULTS: Weaning success
      was present in 76.5% and weaning failure in 17.5% of patients. There were 6% of
      reintubations. The predictive power for RR weaning failure, RR best cut-off point
      > 24 breaths per minute (rpm), was: sensitivity 100%, specificity 85%, and
      accuracy 88% (ROC curve, p < 0.0001). Of the patients with weaning failure, 100%
      were identified by RR during screening (RR cut-off > 24 rpm). There were 15%
      false positives, weaning successes with RR > 24 rpm. CONCLUSION: RR was an
      effective predictor of weaning failure. The best cut-off point was RR > 24 rpm,
      which differed from those reported in the literature (35 and 38 rpm). Only 6% of
      patients were reintubated, but RR or other weaning criteria did not identify
      them.

PMID- 24565085
TI  - Stochastic modelling of biochemical systems of multi-step reactions using a
      simplified two-variable model.
AB  - BACKGROUND: A fundamental issue in systems biology is how to design simplified
      mathematical models for describing the dynamics of complex biochemical reaction
      systems. Among them, a key question is how to use simplified reactions to
      describe the chemical events of multi-step reactions that are ubiquitous in
      biochemistry and biophysics. To address this issue, a widely used approach in
      literature is to use one-step reaction to represent the multi-step chemical
      events. In recent years, a number of modelling methods have been designed to
      improve the accuracy of the one-step reaction method, including the use of
      reactions with time delay. However, our recent research results suggested that
      there are still deviations between the dynamics of delayed reactions and that of
      the multi-step reactions. Therefore, more sophisticated modelling methods are
      needed to accurately describe the complex biological systems in an efficient way.
      RESULTS: This work designs a two-variable model to simplify chemical events of
      multi-step reactions. In addition to the total molecule number of a species, we
      first introduce a new concept regarding the location of molecules in the multi
      step reactions, which is the second variable to represent the system dynamics.
      Then we propose a simulation algorithm to compute the probability for the firing
      of the last step reaction in the multi-step events. This probability function is
      evaluated using a deterministic model of ordinary differential equations and a
      stochastic model in the framework of the stochastic simulation algorithm. The
      efficiency of the proposed two-variable model is demonstrated by the realization
      of mRNA degradation process based on the experimentally measured data.
      CONCLUSIONS: Numerical results suggest that the proposed new two-variable model
      produces predictions that match the multi-step chemical reactions very well. The
      successful realization of the mRNA degradation dynamics indicates that the
      proposed method is a promising approach to reduce the complexity of biological
      systems.

PMID- 24565087
TI  - Malignant hyperthermia in Brazil: analysis of hotline activity in 2009.
AB  - BACKGROUND AND OBJECTIVES: Malignant hyperthermia (MH) is a pharmacogenetic
      disease that causes abnormal hypermetabolic reaction to halogenated anesthetics
      and/or depolarizing muscle relaxants. In Brazil, there is a hotline telephone
      service for MH since 1991, available 24 hours a day in Sao Paulo. This article
      analyzes the activity of the Brazilian hotline service for MH in 2009. METHODS:
      Prospective analysis of all phone calls made to the Brazilian hotline service for
      MH from January to December 2009. RESULTS: Twenty-two phone calls were received:
      21 from the South/Southeast region of Brazil and one from the North region.
      Fifteen calls were requests for general information about MH. Seven were about
      suspected MH acute episodes, two of which were not considered as MH. In five
      episodes compatible with MH, all patients received halogenated volatile
      anesthetics (2, isoflurane; 3, sevoflurane) and one also used succinylcholine;
      there were four men and one woman, with a mean age of 18 years (2-27). The
      problems described in the five MH episodes were tachycardia (5), increased
      expired carbon dioxide (4), hyperthermia (3), acidemia (1), rhabdomyolysis (1),
      and myoglobinuria (1). One patient received dantrolene. All five patients with MH
      episodes were follow-up in the intensive care unit and recovered without
      sequelae. Susceptibility to MH was later confirmed in two patients by in vitro
      muscle contracture test. CONCLUSIONS: The number of calls per year in the
      Brazilian hotline service for MH is still low. The characteristics of MH episode
      were similar to those reported in other countries. The knowledge of MH in Brazil
      needs to be increased.

PMID- 24565088
TI  - Volume replacement therapy during hip arthroplasty using hydroxyethyl starch
      (130/0.4) compared to lactated Ringer decreases allogeneic blood transfusion and
      postoperative infection.
AB  - BACKGROUND AND OBJECTIVES: Hydroxyethyl starch (HES) 130/0.4 is considered an
      effective plasma expander when compared to crystalloids. There is controversy
      around its superiority regarding hemodynamic optimization and about possible
      detrimental effects on coagulation. The aim of this study was to compare the
      effects of HES 130/0.4 to lactated Ringer solution during hip arthroplasty in
      adult patients under spinal anesthesia regarding intraoperative bleeding,
      hemodynamic parameters, coagulation profile, transfusion requirements and
      clinical outcomes. METHODS: In this randomized, controlled trial, 48 patients
      scheduled for hip arthroplasty with spinal anesthesia were randomized into two
      groups: 24 patients were allocated to receive a preload of 15 mL.kg(-1) of HES
      130/0.4 and 24 patients received a preload of 30 mL.kg(-1) lactated Ringer
      solution before surgery. Hemodynamic measurements, hemoglobin concentrations,
      biochemical parameters and coagulation tests were evaluated in three periods
      during surgical procedure. Patients received medical follow-up during their
      hospital stay and up to postoperative 30 days. Primary outcome was the
      requirement of red blood cell transfusion between groups during hospital stay.
      Secondary outcome were hemodynamic parameters, length of hospital stay, mortality
      and occurrence of clinical postoperative complications. RESULTS: Red blood cell
      transfusion was required in 17% of patients in the HES group and in 46% in the
      Ringer group (p = .029). Postoperative infections were more frequently observed
      in the Ringer group (17%) compared to the HES group (0), p = .037. There were no
      significant differences between groups in mortality, hospital length of stay and
      clinical complications other than infection. CONCLUSIONS: During hip
      arthroplasty, patients treated with hypervolemic hemodilution with hydroxyethyl
      starch 130/0.4 required less transfusion and presented lower infection rate
      compared to patients who received lactated Ringer.

PMID- 24565091
TI  - Three-year evaluation of nosocomial infection rates of the ICU.
AB  - BACKGROUND AND OBJECTIVES: Evaluating the incidence of nosocomial and invasive
      device-related infections enables the comparison of the health care associated
      infection (HAI) between the intensive care units of different hospitals and
      different units in the same hospital. MATERIAL AND METHODS: A retrospective
      surveillance study was performed to identify nosocomial infections, device
      related infections rates, and causal agents from January 2007 through December
      2010 in the Anesthesiology Intensive care unit (ICU). HAI were defined according
      to the CDC (Centers for Disease Control and Prevention) criteria, and invasive
      device-related infections were defined according to National Nosocomial Infection
      Surveillance System (NNIS) criteria. RESULTS: During a two-year period, 939
      patients were analyzed throughout a total of 7,892 patient- days. The rates of
      HAI were 53% in 2007, 29.15% in 2008, 28.85% in 2009 while 16.62% in 2010. Most
      common HAI was blood stream infection. The rate of soft tissue and skin infection
      was the second most common. Overall, the most common agents were Gram(-) 56.68%,
      Gram(+) 31.02% and Candida spp 12.3% among patients with nosocomial infections.
      CONCLUSIONS: The incidence of HAI in the ICU of our hospital was high, compared
      to the Turkish overall rates obtained at the Refik Saydam Center in 2007. When
      the rates of device-related infections between 2007 and 2008 were compared, they
      were higher in 2007. The rates of device- related infections were diminished in
      2008 to below-national mean rates by infection control measures. Since the rate
      of urinary catheter-related infections are still high, we should exert continuous
      efforts for infection control.

PMID- 24565090
TI  - Pharmacodynamic evaluation and physical/chemical analysis of two formulations of
      propofol used in target-controlled infusion.
AB  - BACKGROUND AND OBJECTIVES: There are several formulations of propofol available
      to the anesthesiologist for clinical use. The aim of this study was to analyze
      the physicochemical properties, pharmacodynamic effect, and pharmaceutical and
      clinical equivalence of the reference drug propofol as well as a similar
      formulation. METHOD: Sixteen volunteers were enrolled in this randomized, double
      blind, and paired study of Diprivan(r) and Propovan(r) formulations. Formulations
      were given as target-controlled infusion with target concentration of 3.0 MUg.mL(
      1) for 15 minutes. Variables studied were the area under the curve (AUC) of the
      bispectral index (BIS) graph regarding time, minimum BIS reached and time to
      reach it, and recovery time. The two formulations were sent to analysis of
      particle size of lipid emulsion, surface potential, and active principle
      quantification. RESULTS: There was no difference between the formulations when
      comparing AUC, minimum BIS reached and time to reach it. The similar formulation
      recovery time was lower compared to the reference formulation (eight and 10 min,
      respectively, p = 0.014). Mean particle size of lipid emulsion, surface
      potential, and active ingredient quantification were similar for both
      formulations. CONCLUSION: There was no clinically significant difference between
      the use of propofol, reference Diprivan(r), and the similar Propovan(r) during
      infusion. However, the recovery time was longer with the reference drug. Although
      analysis of both formulations studied show similar results regarding its
      physicochemical characterization, further studies should be conducted to justify
      this difference.

PMID- 24565092
TI  - Ropivacaine, articaine or combination of ropivacaine and articaine for epidural
      anesthesia in cesarean section: a randomized, prospective, double-blinded study.
AB  - BACKGROUND AND OBJECTIVES: Initiation of epidural anesthesia with long-lasting
      local anesthetics consumes a significant amount of time, which could be
      problematic in busy obstetric anesthesia suites. We have hypothesized that a
      combination of articaine and ropivacaine provides faster onset and even an early
      recovery of sensory-motor block characteristics. METHODS: Sixty term parturients
      scheduled to have elective cesarean section were randomly allocated into three
      groups to receive either 20 mL 2% articaine (Group A), 10 mL 2% articaine + 10 mL
      0.75% ropivacaine (Group AR) or 20 mL 0.75% ropivacaine (Group R) via lumbar
      epidural catheter. The onset time of sensory block to T10, T6 and maximum sensory
      block level, time to two segments regression from maximum sensory block level,
      onset time and duration of motor block were all recorded. Intraoperative and
      postoperative additional analgesic requirements were also recorded. RESULTS:
      Demographic data were similar. The onset times of sensorial block to T10 and T6
      were significantly shorter in Groups A and AR in comparison with Group R (p <
      0.05). The onset times of motor block were similar in all groups, but a more
      intense motor block was observed in Group R (p < 0.05). Two segments regression
      time and motor block durations were significantly shorter in Groups A and AR in
      comparison with Group R (p < 0.05). Intraoperative supplementary analgesic
      requirements were higher in Group A than in the other two groups (p < 0.05).
      CONCLUSION: A combination of 2% articaine and 0.75% ropivacaine for epidural
      anesthesia in a cesarean section should be preferred over epidural 0.75%
      ropivacaine alone.

PMID- 24565093
TI  - Hemostatic resuscitation in traumatic hemorrhagic shock: case report.
AB  - BACKGROUND AND OBJECTIVES: The aim of this paper is to report a case in which the
      damage control resuscitation (DCR) approach was successfully used to promote
      hemostatic resuscitation in a polytraumatized patient with severe hemorrhagic
      shock. CASE REPORT: Female patient, 32 years of age, with severe hemorrhagic
      shock due to polytrauma with hip fracture, who developed acidosis, coagulopathy,
      and hypothermia. During fluid resuscitation, the patient received blood products
      transfusion of fresh frozen plasma/packed red blood cells/platelet concentrate at
      a ratio of 1:1:1 and evolved intraoperatively with improvement in perfusion
      parameters without requiring vasoactive drugs. At the end of the operation, the
      patient was taken to the intensive care unit and discharged on the seventh
      postoperative day CONCLUSION: : The ideal management of traumatic hemorrhagic
      shock is not yet established, but the rapid control of bleeding and perfusion
      recovery and well-defined therapeutic protocols are fundamental to prevent
      progression of coagulopathy and refractory shock.

PMID- 24565094
TI  - Bronchial injury and pneumothorax after reintubation using an airway exchange
      catheter.
AB  - BACKGROUND AND OBJECTIVES: We report a case of pneumothorax caused by a bronchial
      perforation during a reintubation using an airway exchange catheter (AEC) in a
      patient with a head and neck cancer. CASE REPORT: A 53 year old man with
      oropharynx carcinoma was admitted to ICU for severe pneumonia and severe acute
      respiratory distress syndrome (ARDS). The patient was recognized as a difficult
      to-intubate patient and an endotracheal tube (ETT) was inserted through a
      bronchoscope. After one week of treatment, it was observed an endotracheal cuff
      perforation. Exchanging the endotracheal tube was necessary to achieve
      satisfactory pulmonary ventilation. An AEC Cook 14 was used to perform the
      reintubation. After reintubation, the patient presented a worsening in oxygen
      saturation and a chest radiography (CXR) revealed a large pneumothorax. A chest
      tube was inserted and we observed immediate improvement in oxygen saturation. A
      repeat CXR confirmed correct positioning of the chest tube and reexpansion of the
      right lung. A bronchoscopy performed showed a posterior laceration in the right
      main bronchus. The patient was extubated the following day. After four days, the
      chest tube was removed. A CXR performed a day after chest tube removal revealed a
      small right upper pneumothorax, but the patient remained asymptomatic.
      CONCLUSIONS: Airway exchange catheter is a valuable tool to handle with difficult
      to-intubate patients. Although the physicians generally focus their attention in
      avoid barotrauma--caused by oxygen supplement or jet ventilation through AEC-
      concern for insertion technique can minimize life threatening complications and
      increase the safety of AEC.

PMID- 24565095
TI  - Use of sugammadex in Strumpell-Lorrain disease: a report of two cases.
AB  - CONTENT: Strumpell-Lorrain disease--or familial spastic paraplegia (FSP)--is a
      rare hereditary neurological disorder, mainly characterized by variable degrees
      of stiffness and weakening of the muscles, with cognitive impairment, deafness,
      and ataxia in the more severe cases. We describe two female siblings with FSP
      programmed for cholecystectomy and subtotal colectomy, respectively, and also how
      we dealt with the anesthetic management in both cases and review the literature
      on this disease in relation to anesthesia.

PMID- 24565096
TI  - Anesthetics, cerebral protection and preconditioning.
AB  - BACKGROUND AND OBJECTIVES: Several studies demonstrate that cerebral
      preconditioning is a protective mechanism against a stressful situation.
      Preconditioning determinants are described, as well as the neuroprotection
      provided by anesthetic and non-anesthetics agents. CONTENT: Review based on the
      main articles addressing the pathophysiology of ischemia-reperfusion and neuronal
      injury and pharmacological and non-pharmacological factors (inflammation,
      glycemia, and temperature) related to the change in response to ischemia
      reperfusion, in addition to neuroprotection induced by anesthetic use.
      CONCLUSIONS: The brain has the ability to protect itself against ischemia when
      stimulated. The elucidation of this mechanism enables the application of
      preconditioning inducing substances (some anesthetics), other drugs, and non
      pharmacological measures, such as hypothermia, aimed at inducing tolerance to
      ischemic lesions.

PMID- 24565097
TI  - Neurotoxic effects of intrathecal magnesium sulphate.
AB  - BACKGROUND AND OBJECTIVES: To assess the potential neurotoxic effects at the
      ultrastructural level of magnesium sulfate administered intrathecally as a single
      or multi-dose. METHODS: Our study was conducted with 24 Sprague-Dawley rats that
      weighed 250-300 g. After a 4-hour fast, the rats were given 10 mg.kg(-1) xylazine
      chloride intraperitoneal and then randomly allocated into three groups. Group I
      (n = 8) received 0.9% normal saline, Group II (n = 8) was given one intrathecal
      injection of 0.02 mL of 15% magnesium sulphate, and Group III (n = 8) was given
      0.02 mL of 15% magnesium sulphate once a day for seven days. The injections were
      given within 0.40x50 mm from the lumbar area. After seven days, the animals were
      sacrificed under anesthesia with an aortic injection of 10% formaldehyde and
      their tissues were fixed. The medulla spinalis was then examined and
      histopathologically evaluated under an electron microscope. The Kruskal-Wallis
      test was used for statistical evaluation. A value of p < .05 was considered to be
      statistically significant. RESULTS: Significant neurodegeneration was detected in
      rats given single or repeated magnesium sulphate injections compared to the
      control group. The histopathological evaluation score of this group was also
      high. CONCLUSIONS: Based on electron microscopic examination, we found that
      intrathecal magnesium sulphate administration induced neurodegeneration.

PMID- 24565098
TI  - Pain management in burn patients.
AB  - BACKGROUND AND OBJECTIVES: Despite advances, inappropriate analgesic treatment
      for burn patients is still seen. The objective of this review was to collect data
      on pain management in burn patients. CONTENT: We reviewed the mechanisms of pain,
      burn patient assessment, as well as pharmacological and non-pharmacological
      treatment. CONCLUSION: Pain management in burn patients is still a challenge for
      the multidisciplinary team. Frequent and continuous evaluation of the patient's
      response is very important due to the various stages that the hospitalized burn
      patient goes through, as well as a combination therapy with analgesic and non
      pharmacological measures. Understanding the complexity of the pathophysiological,
      psychological, and biochemical changes a burn patient presents is the first step
      to achieve success in analgesic management.

PMID- 24565099
TI  - Anesthetic management of a patient with Brugada syndrome--the use of sugammadex
      in major abdominal surgery.

PMID- 24565100
TI  - Precipitation in Gallipoli: sugammadex / amiodarone & sugammadex / dobutamine &
      sugammadex / protamine.

PMID- 24565101
TI  - MicroRNA-26b suppresses the NF-kappaB signaling and enhances the chemosensitivity
      of hepatocellular carcinoma cells by targeting TAK1 and TAB3.
AB  - BACKGROUND: Abnormal activation of the NF-kappaB pathway is closely related to
      tumorigenesis and chemoresistance. Therefore, microRNAs that possess the NF
      kappaB inhibitory activity may provide novel targets for anti-cancer therapy. miR
      26 family members have been shown to be frequently downregulated in
      hepatocellular carcinoma (HCC) and correlated with the poor survival of HCC
      patients. To date, there is no report disclosing the regulatory role of miR-26 on
      the NF-kappaB pathway and its biological significance. METHODS: The effects of
      miR-26b on the NF-kappaB signaling pathway and the chemosensitivity of cancer
      cells were examined in two HCC cell lines, QGY-7703 and MHCC-97H, using both gain
      and loss-of-function studies. The correlation between miR-26b level and
      apoptosis rate was further investigated in clinical HCC specimens. RESULTS: Both
      TNFalpha and doxorubicin treatment activated the NF-kappaB signaling pathway in
      HCC cells. However, the restoration of miR-26b expression significantly inhibited
      the phosphorylation of IkappaBalpha and p65, blocked the nuclear translocation of
      NF-kappaB, reduced the NF-kappaB reporter activity, and consequently abrogated
      the expression of NF-kappaB target genes in TNFalpha or doxorubicin-treated HCC
      cells. Furthermore, the ectopic expression of miR-26b dramatically sensitized HCC
      cells to the doxorubicin-induced apoptosis, whereas the antagonism of miR-26b
      attenuated cell apoptosis. Consistently, the miR-26b level was positively
      correlated with the apoptosis rate in HCC tissues. Subsequent investigations
      revealed that miR-26b inhibited the expression of TAK1 and TAB3, two positive
      regulators of NF-kappaB pathway, by binding to their 3'-untranslated region.
      Moreover, knockdown of TAK1 or TAB3 phenocopied the effects of miR-26b
      overexpression. CONCLUSIONS: These data suggest that miR-26b suppresses NF-kappaB
      signaling and thereby sensitized HCC cells to the doxorubicin-induced apoptosis
      by inhibiting the expression of TAK1 and TAB3. Our findings highlight miR-26b as
      a potent inhibitor of the NF-kappaB pathway and an attractive target for cancer
      treatment.

PMID- 24565102
TI  - The effectiveness of interventions targeting specific out-of-home food outlets:
      protocol for a systematic review.
AB  - BACKGROUND: Eating out of the home has been associated with higher intakes of
      energy and fat and lower micronutrient intakes, as well as the development of
      obesity. Out-of-home food outlets (OHFOs) and the foods obtained from these
      outlets are an ideal target for interventions to improve diet and tackle obesity.
      This systematic review will explore the evidence for the effectiveness of
      promoting healthy behaviour through interventions that modify food practices in
      specific OHFOs. METHODS/DESIGN: We will search the databases MEDLINE, EMBASE,
      CINAHL, PsycINFO, ASSIA and the NHS Economic Evaluation Database for studies that
      have evaluated interventions conducted in an OHFO that aim to promote healthier
      menu offerings. OHFOs which are not openly accessible to the general public and
      supermarkets will be excluded. Included study designs will be randomised
      controlled trials, non-randomised controlled trials, controlled before-after
      studies, interrupted time series studies and evaluations of single interventions
      where outcome measures were assessed at least once pre and post-intervention
      (repeated measures studies). DISCUSSION: This systematic review aims to
      synthesise the available evidence with regard to interventions that aim to change
      specific OHFOs in order to promote healthier menu offerings. The findings of this
      review will provide information on the types of interventions that have been
      evaluated and the context in which they are set, and provide insights into what
      interventions, and intervention functions, are most effective in different OHFO
      settings, along with any important innovation, implementation and cost
      implications.The review has been registered with PROSPERO (registration no.
      CRD42013006931).

PMID- 24565103
TI  - Sheathed versus standard speculum for visualization of the cervix.
AB  - OBJECTIVE: To determine whether modifying a plastic speculum with a flexible
      sheath would improve visualization and decrease pain during vaginal examination.
      METHODS: We conducted a prospective randomized controlled trial of 136 women
      undergoing vaginal speculum examination at an outpatient obstetrics and
      gynecology faculty practice. Patients underwent examination via a standardized
      technique with either a medium-sized plastic speculum (standard) or an identical
      speculum modified with a flexible polypropylene sheath (sheathed). Investigators
      recorded the percentage of the cervix visualized. After speculum insertion,
      patients recorded pain using a 10-cm visual analog scale. RESULTS: There were no
      substantial demographic differences between the standard (n=67) and the sheathed
      (n=68) groups. Investigators were able to visualize a significantly greater
      percentage of the cervix using the sheathed speculum compared with the standard
      speculum (95.1%+/-8.2% vs. 78.2%+/-18.4%; P<0.001), representing a 21.6%
      improvement in visualization, and were able to visualize the entire cervix in 42
      (61.8%) patients when using the sheathed speculum compared with 11 (16.4%)
      patients undergoing standard speculum examination (P<0.001). Patients undergoing
      examination with the sheathed speculum reported a nonsignificant decrease in pain
      scores (1.0 vs 1.2; P=0.087). CONCLUSION: A sheathed speculum significantly
      improves visualization of the cervix, without compromising patient comfort.
      ClinicalTrials.gov:NCT01670630.

PMID- 24565104
TI  - Corbi: a new R package for biological network alignment and querying.
AB  - In the last decade, plenty of biological networks are built from the large scale
      experimental data produced by the rapidly developing high-throughput techniques
      as well as literature and other sources. But the huge amount of network data have
      not been fully utilized due to the limited biological network analysis tools. As
      a basic and essential bioinformatics method, biological network alignment and
      querying have been applied in many fields such as predicting new protein-protein
      interactions (PPI). Although many algorithms were published, the network
      alignment and querying problems are not solved satisfactorily. In this paper, we
      extended CNetQ, a novel network querying method based on the conditional random
      fields model, to solve network alignment problem, by adopting an iterative bi
      directional mapping strategy. The new method, called CNetA, was compared with
      other four methods on fifty simulated and three real PPI network alignment
      instances by using four structural and five biological measures. The
      computational experiments on the simulated data, which were generated from a
      biological network evolutionary model to validate the effectiveness of network
      alignment methods, show that CNetA gets the best accuracy in terms of both nodes
      and networks. For the real data, larger biological conserved subnetworks and
      larger connected subnetworks were identified, compared with the structural
      dominated methods and the biological-dominated methods, respectively, which
      suggests that CNetA can better balances the biological and structural
      similarities. Further, CNetQ and CNetA have been implemented in a new R package
      Corbi (http://doc.aporc.org/wiki/Corbi), and freely accessible and easy used web
      services for CNetQ and CNetA have also been constructed based on the R package.
      The simulated and real datasets used in this paper are available for downloading
      at http://doc.aporc.org/wiki/CNetA/. 

PMID- 24565105
TI  - Semi-supervised method for biomedical event extraction.
AB  - BACKGROUND: Biomedical extraction based on supervised machine learning still
      faces the problem that a limited labeled dataset does not saturate the learning
      method. Many supervised learning algorithms for bio-event extraction have been
      affected by the data sparseness. METHODS: In this study, a semi-supervised method
      for combining labeled data with large scale of unlabeled data is presented to
      improve the performance of biomedical event extraction. We propose a set of rich
      feature vector, including a variety of syntactic features and semantic features,
      such as N-gram features, walk subsequence features, predicate argument structure
      (PAS) features, especially some new features derived from a strategy named Event
      Feature Coupling Generalization (EFCG). The EFCG algorithm can create useful
      event recognition features by making use of the correlation between two sorts of
      original features explored from the labeled data, while the correlation is
      computed with the help of massive amounts of unlabeled data. This introduced EFCG
      approach aims to solve the data sparse problem caused by limited tagging corpus,
      and enables the new features to cover much more event related information with
      better generalization properties. RESULTS: The effectiveness of our event
      extraction system is evaluated on the datasets from the BioNLP Shared Task 2011
      and PubMed. Experimental results demonstrate the state-of-the-art performance in
      the fine-grained biomedical information extraction task. CONCLUSIONS: Limited
      labeled data could be combined with unlabeled data to tackle the data sparseness
      problem by means of our EFCG approach, and the classified capability of the model
      was enhanced through establishing a rich feature set by both labeled and
      unlabeled datasets. So this semi-supervised learning approach could go far
      towards improving the performance of the event extraction system. To the best of
      our knowledge, it was the first attempt at combining labeled and unlabeled data
      for tasks related biomedical event extraction.

PMID- 24565106
TI  - A conservation and biophysics guided stochastic approach to refining docked
      multimeric proteins.
AB  - BACKGROUND: We introduce a protein docking refinement method that accepts
      complexes consisting of any number of monomeric units. The method uses a scoring
      function based on a tight coupling between evolutionary conservation, geometry
      and physico-chemical interactions. Understanding the role of protein complexes in
      the basic biology of organisms heavily relies on the detection of protein
      complexes and their structures. Different computational docking methods are
      developed for this purpose, however, these methods are often not accurate and
      their results need to be further refined to improve the geometry and the energy
      of the resulting complexes. Also, despite the fact that complexes in nature often
      have more than two monomers, most docking methods focus on dimers since the
      computational complexity increases exponentially due to the addition of monomeric
      units. RESULTS: Our results show that the refinement scheme can efficiently
      handle complexes with more than two monomers by biasing the results towards
      complexes with native interactions, filtering out false positive results. Our
      refined complexes have better IRMSDs with respect to the known complexes and
      lower energies than those initial docked structures. CONCLUSIONS: Evolutionary
      conservation information allows us to bias our results towards possible
      functional interfaces, and the probabilistic selection scheme helps us to escape
      local energy minima. We aim to incorporate our refinement method in a larger
      framework which also enables docking of multimeric complexes given only monomeric
      structures.

PMID- 24565107
TI  - Genomic characterization of a Helicobacter pylori isolate from a patient with
      gastric cancer in China.
AB  - BACKGROUND: Helicobacter pylori is well known for its relationship with the
      occurrence of several severe gastric diseases. The mechanisms of pathogenesis
      triggered by H. pylori are less well known. In this study, we report the genome
      sequence and genomic characterizations of H. pylori strain HLJ039 that was
      isolated from a patient with gastric cancer in the Chinese province of
      Heilongjiang, where there is a high incidence of gastric cancer. To investigate
      potential genomic features that may be involved in pathogenesis of carcinoma, the
      genome was compared to three previously sequenced genomes in this area. RESULT:
      We obtained 42 contigs with a total length of 1,611,192 bp and predicted 1,687
      coding sequences. Compared to strains isolated from gastritis and ulcers in this
      area, 10 different regions were identified as being unique for HLJ039; they
      mainly encoded type II restriction-modification enzyme, type II m6A methylase,
      DNA-cytosine methyltransferase, DNA methylase, and hypothetical proteins. A
      unique 547-bp fragment sharing 93% identity with a hypothetical protein of
      Helicobacter cinaedi ATCC BAA-847 was not present in any other previous H. pylori
      strains. Phylogenetic analysis based on core genome single nucleotide
      polymorphisms shows that HLJ039 is defined as hspEAsia subgroup, which belongs to
      the hpEastAsia group. CONCLUSION: DNA methylations, variations of the genomic
      regions involved in restriction and modification systems, are the "hot" regions
      that may be related to the mechanism of H. pylori-induced gastric cancer. The
      genome sequence will provide useful information for the deep mining of potential
      mechanisms related to East Asian gastric cancer.

PMID- 24565108
TI  - CGPredictor: a systematic integrated analytic tool for mining and examining
      genome-scale cancer independent prognostic epigenetic marker panels.
AB  - BACKGROUND: Tumor biomarkers are potentially useful in several ways such as the
      identification of individuals at increased risk of developing cancer, in
      screening for early malignancies and in aiding cancer diagnoses; tumor biomarkers
      may also be used for determining prognosis, predicting therapeutic response,
      patient tracking following curative surgery for cancer and for monitoring
      therapy. Epigenetic alterations, especially aberrant DNA methylation, are
      recognized as common molecular alterations in a variety of tumors and also occur
      during the development of tumors. The Cancer Grade Predictor (CGPredictor) is an
      extendable package with functions designed to facilitate systematic integrated
      and rapid analysis of high-throughput methylation through the use of most self
      similarity subgroups of patients supported by various validating examinations
      with regarded to survival outcome to obtain the identity of the target predictor.
      RESULTS: We used high-grade serous ovarian cancer (HGSOC) and invasive breast
      carcinoma (BRCA) to demonstrate the usefulness of the CGPredictor package. The
      clustering results and the identity predictors worked well and efficiently in
      producing significant results after various tests were used to validate the
      usefulness of CGPredictor package. Also, some of the markers for either the HGSOC
      or BRCA marker panel have been previously reported to reveal significant results.
      Even when performed using a different platform with an independent large
      population BRCA dataset for validation, the identity predictor provided an
      accurate assessment of patient conditions and produced significant results.
      CONCLUSIONS: CGPredictor package is not a customized analysis tool designed
      specifically for the identification of only one or a few specific types of cancer
      but can be applied more broadly; moreover, the results indicate that the
      extracted predictors may worthy of consideration for further clinical testing to
      identify their potential usefulness for clinical molecular diagnosis and targeted
      treatments of patients with HGSOC and BRCA. So, the use of CGPredictor is
      feasible for examining the statistical significance of specific markers of
      interest and shows great potential for use with other types of cancers for cancer
      biomarker mining.

PMID- 24565109
TI  - Microphysiological systems and low-cost microfluidic platform with analytics.
AB  - A multiorgan, functional, human in vitro assay system or 'Body-on-a-Chip' would
      be of tremendous benefit to the drug discovery and toxicology industries, as well
      as providing a more biologically accurate model for the study of disease as well
      as applied and basic biological research. Here, we describe the advances our team
      has made towards this goal, as well as the most pertinent issues facing further
      development of these systems. Description is given of individual organ models
      with appropriate cellular functionality, and our efforts to produce human
      iterations of each using primary and stem cell sources for eventual incorporation
      into this system. Advancement of the 'Body-on-a-Chip' field is predicated on the
      availability of abundant sources of human cells, capable of full differentiation
      and maturation to adult phenotypes, for which researchers are largely dependent
      on stem cells. Although this level of maturation is not yet achievable in all
      cell types, the work of our group highlights the high level of functionality that
      can be achieved using current technology, for a wide variety of cell types. As
      availability of functional human cell types for in vitro culture increases, the
      potential to produce a multiorgan in vitro system capable of accurately
      reproducing acute and chronic human responses to chemical and pathological
      challenge in real time will also increase. 

PMID- 24565111
TI  - Acoustic shock controversies.
AB  - BACKGROUND: The diagnosis 'acoustic shock' has been made increasingly in the
      health care industry in recent years. This paper aims to question the validity of
      acoustic shock as an organic pathological entity. METHODS: The experiences of 16
      individuals diagnosed as having acoustic shock, within a medico-legal practice,
      are reviewed. RESULTS: The commonest symptom was otalgia, followed by noise
      sensitivity, tinnitus, hearing disturbance and dizziness. CONCLUSION: The
      presence of noise-limiting technology in the workplace, the variation in the
      nature of the acoustic incident involved (ranging from a shriek, through feedback
      noise, to a male voice), and the marked variation in the time of symptom onset
      (following the acoustic incident) all suggest that the condition termed acoustic
      shock is predominantly psychogenic. Cases of pseudohypacusis indicate that
      malingering is a factor in some cases. Clusters of acoustic shock events
      occurring in the same call centres suggest that hysteria may play a part. The
      condition is usually only seen when work-related issues are apparent.

PMID- 24565110
TI  - Hydrolyzed protein supplementation improves protein content and peroxidation of
      skeletal muscle by adjusting the plasma amino acid spectrums in rats after
      exhaustive swimming exercise: a pilot study.
AB  - BACKGROUND: This study was designed to evaluate the effects of hydrolyzed protein
      supplementation upon skeletal muscle total protein and peroxidation in rats
      following exhaustive swimming exercise. METHODS: Twenty-four rats were randomized
      to 4 experimental groups (n = 6 per group): control group fed standard diet
      without exercise (SD), exercise (EX), exercise plus standard diet for 72 hours
      (EX + SD), and exercise plus standard diet supplemented with hydrolyzed protein
      (2 g/kg/d) for 72 hours (EX + HP). Immediately following exercise, the EX group
      was euthanized for collecting plasma and skeletal muscle samples. The EX + SD and
      EX + HP groups were fed their respective diets for 72 hour still plasma and
      skeletal muscle collection. Skeletal muscle samples were used to measure levels
      of total protein (TP), malondialdehyde (MDA), and protein carbonyl (PC). Plasma
      samples were used to analyze the amino acids spectrum. RESULTS: Compared with the
      EX + SD, EX + HP presented the significantly increased TP (P = 0.02) and
      decreased MDA and PC levels (P = 0.035). MDA was negatively correlated with the
      methionine levels. Moreover, EX + HP maintained higher levels of plasmaleucine,
      isoleucine, and methionine than EX + SD, which may be associated with the
      increased skeletal muscle TP levels observed (P < 0.05). CONCLUSIONS: These
      results collectively suggest that hydrolyzed protein supplementation can improve
      skeletal muscle TP and ameliorate peroxidation damage in rats subjected to
      exhaustive exercise stress, which may be, at least in part, related with the
      maintenance of plasma leucine, isoleucine, and methionine levels.

PMID- 24565112
TI  - Palliative care in children with spinal muscular atrophy type I: What do they
      need?
AB  - OBJECTIVE: Our aim was to describe the clinical evolution and needs of children
      with spinal muscular atrophy type I treated in a domiciliary palliative care
      program. METHOD: We undertook a retrospective chart review of nine consecutive
      patients. Descriptions of the clinical and demographic profile of children with
      spinal muscular atrophy (SMA) type I were referred to a pediatric palliative care
      team (PPCT). RESULTS: Six males and three females were admitted to the PPCT, all
      before six months of age, except for one afflicted with SMA type I with
      respiratory distress. The median time of attention was 57 days (range 1-150). The
      domiciliary attention mainly consisted of respiratory care. The patient with SMA
      type I with respiratory distress required domiciliary mechanical ventilation by
      tracheotomy. In all cases, a nasogastric tube (NT) was indicated. As end-of-life
      care, eight required morphine to manage the dyspnea, four received it only by
      enteral (oral or NT) administration, and four received it first by enteral
      administration with continuous subcutaneous infusion (CSI) later. Three of the
      four patients with CSI also received benzodiazepines. While they were attended by
      the PPCT, none required hospital admission. All the patients died at home except
      for the one attended to for just one day. SIGNIFICANCE OF RESULTS: Domiciliary
      care for these patients is possible. The respiratory morbidity and its management
      are the main issues. Application of an NT is useful to maintain nutritional
      balance. Morphine administration is necessary to manage the dyspnea. Palliative
      sedation is not always necessary.

PMID- 24565115
TI  - Automated skin biopsy histopathological image annotation using multi-instance
      representation and learning.
AB  - With digitisation and the development of computer-aided diagnosis,
      histopathological image analysis has attracted considerable interest in recent
      years. In this article, we address the problem of the automated annotation of
      skin biopsy images, a special type of histopathological image analysis. In
      contrast to previous well-studied methods in histopathology, we propose a novel
      annotation method based on a multi-instance learning framework. The proposed
      framework first represents each skin biopsy image as a multi-instance sample
      using a graph cutting method, decomposing the image to a set of visually disjoint
      regions. Then, we construct two classification models using multi-instance
      learning algorithms, among which one provides determinate results and the other
      calculates a posterior probability. We evaluate the proposed annotation framework
      using a real dataset containing 6691 skin biopsy images, with 15 properties as
      target annotation terms. The results indicate that the proposed method is
      effective and medically acceptable. 

PMID- 24565116
TI  - Letter to the editor regarding "A questionnaire-based study on parental
      satisfaction with a universal newborn hearing screening program in Kuala Lumpur,
      Malaysia".

PMID- 24565113
TI  - Expression of glutathione, glutathione peroxidase and glutathione S-transferase
      pi in canine mammary tumors.
AB  - BACKGROUND: Glutathione (GSH) is one of the most important agents of the
      antioxidant defense system of the cell because, in conjunction with the enzymes
      glutathione peroxidase (GSH-Px) and glutathione S transferase pi (GSTpi), it
      plays a central role in the detoxification and biotransformation of
      chemotherapeutic drugs. This study evaluated the expression of GSH and the GSH-Px
      and GSTpi enzymes by immunohistochemistry in 30 canine mammary tumors, relating
      the clinicopathological parameters, clinical outcome and survival of the bitches.
      In an in vitro study, the expression of the genes glutamate cysteine ligase
      (GCLC) and glutathione synthetase (GSS) that synthesize GSH and GSH-Px gene were
      verified by qPCR and subjected to treatment with doxorubicin, to check the
      resistance of cancer cells to chemotherapy. RESULTS: The immunohistochemical
      expression of GSH, GSH-Px and GSTpi was compared with the clinical and
      pathological characteristics and the clinical outcome in the bitches, including
      metastasis and death.The results showed that high immunoexpression of GSH was
      correlated to the absence of tumor ulceration and was present in dogs without
      metastasis (P < 0.05). There was significant correlation of survival with the
      increase of GSH (P < 0.05). The expression of the GSH-Px and GSTpi enzymes showed
      no statistically significant correlation with the analyzed variables (p > 0.05).
      The analysis of the relative expression of genes responsible for the synthesis of
      GSH (GCLC and GSS) and GSH-Px by quantitative PCR was done with cultured cells of
      10 tumor fragments from dogs with mammary tumors.The culture cells showed a
      decrease in GCLC and GSS expression when compared with no treated cells (P <
      0.05). High GSH immunoexpression was associated with better clinical outcomes.
      CONCLUSION: Therefore, high expression of the GSH seems to play an important role
      in the clinical outcome of patients with mammary tumors and suggest its use as
      prognostic marker. The in vitro doxorubicin treatment significantly reduces the
      expression of GCLC and GSS genes so we can consider them to be candidates for
      predictive markers of therapeutic response in mammary cancer.

PMID- 24565114
TI  - Pathway-gene identification for pancreatic cancer survival via doubly regularized
      Cox regression.
AB  - BACKGROUND: Recent global genomic analyses identified 69 gene sets and 12 core
      signaling pathways genetically altered in pancreatic cancer, which is a highly
      malignant disease. A comprehensive understanding of the genetic signatures and
      signaling pathways that are directly correlated to pancreatic cancer survival
      will help cancer researchers to develop effective multi-gene targeted,
      personalized therapies for the pancreatic cancer patients at different stages. A
      previous work that applied a LASSO penalized regression method, which only
      considered individual genetic effects, identified 12 genes associated with
      pancreatic cancer survival. RESULTS: In this work, we integrate pathway
      information into pancreatic cancer survival analysis. We introduce and apply a
      doubly regularized Cox regression model to identify both genes and signaling
      pathways related to pancreatic cancer survival. CONCLUSIONS: Four signaling
      pathways, including Ion transport, immune phagocytosis, TGFbeta
      (spermatogenesis), regulation of DNA-dependent transcription pathways, and 15
      genes within the four pathways are identified and verified to be directly
      correlated to pancreatic cancer survival. Our findings can help cancer
      researchers design new strategies for the early detection and diagnosis of
      pancreatic cancer.

PMID- 24565117
TI  - Addressing tensions when popular media and evidence-based care collide.
AB  - BACKGROUND: Health care news stories have the potential to inform and educate
      news consumers and health-care consumers about the tradeoffs involved in health
      care decisions about treatments, tests, products, and procedures. These stories
      have the potential to influence not only individual decision making but also the
      broader public dialogue about health-care reform. For the past 7 years, a Web
      based project called http://HealthNewsReview.org has evaluated news stories to
      try to improve health-care journalism and the quality and flow of information to
      consumers. ANALYSIS: http://HealthNewsReview.org applies 10 standardized criteria
      to the review of news stories that include claims about medical interventions.
      Two or three reviewers evaluate each story. The team has evaluated more than
      1,800 stories by more than a dozen leading U.S. news organizations. About 70%
      have received unsatisfactory scores based on application of these criteria:
      reporting on costs, quantifying potential benefits, and quantifying potential
      harms. CONCLUSIONS: Inaccurate, imbalanced, incomplete news stories may drown out
      more careful scrutiny of the evidence by many influential news organizations.
      Unquestioned claims and assertions about the benefits of medical interventions
      are passed on to the American public daily by journalists who are supposed to vet
      independently any such claims. Communication about these issues is, in itself, a
      major health-policy issue.

PMID- 24565119
TI  - Tick-borne pathogens in northwestern California, USA.

PMID- 24565120
TI  - Good practice guidelines for biomarker discovery from array data: a case study
      for breast cancer prognosis.
AB  - BACKGROUND: Biomarker discovery holds the promise for advancing personalized
      medicine as the biomarkers can help match patients to optimal treatment to
      improve patient outcomes. However, serious concerns have been raised because very
      few molecular biomarkers or signatures discovered from high dimensional array
      data can be successfully validated and applied to clinical use. We propose good
      practice guidelines as well as a novel tool for biomarker discovery and use
      breast cancer prognosis as a case study to illustrate the proposed approach.
      RESULTS: We applied the proposed approach to a publicly available breast cancer
      prognosis dataset and identified small numbers of predictive markers for patient
      subpopulations stratified by clinical variables. Results from an independent
      cross-platform validation set show that our model compares favorably to other
      gene signature and clinical variable based prognostic tools. About half of the
      discovered candidate markers can individually achieve very good performance,
      which further demonstrate the high quality of feature selection. These candidate
      markers perform extremely well for young patient with estrogen receptor-positive,
      lymph node-negative early stage breast cancers, suggesting a distinct subset of
      these patients identified by these markers is actually at high risk of recurrence
      and may benefit from more aggressive treatment than current practice. CONCLUSION:
      The results show that by following good practice guidelines, we can identify
      highly predictive genes in high dimensional breast cancer array data. These
      predictive genes have been successfully validated using an independent cross
      platform dataset.

PMID- 24565121
TI  - Occupational fatigue: Impact on anesthesiologist's health and the safety of
      surgical patients.

PMID- 24565122
TI  - The effects of nitrous oxide on controlled hypotension during low flow
      anesthesia.
AB  - BACKGROUND AND OBJECTIVES: We investigated the effect of Nitrous Oxide (N2O) on
      controlled hypotension in low-flow isoflurane-dexmedetomidine anesthesia in terms
      of hemodynamics, anesthetic consumption, and costs. METHODS: We allocated forty
      patients randomly into two equal groups. We then maintained dexmedetomidine
      infusion (0.1 MUg.kg-1.min-1) for 10 minutes. Next, we continued it until the
      last 30 minutes of the operation at a dose of 0.7 MUg.kg(-1).hour(-1). We
      administered thiopental (4-6 mg. kg(-1)) and 0.08-0.12 mg.kg(-1) vecuronium
      bromide at induction for both groups. We used isoflurane (2%) for anesthesia
      maintenance. Group N received a 50% O2-N2O mixture and Group A received 50% O 
      air mixture as carrier gas. We started low-flow anesthesia (1 L.min(-1)) after a
      10-minute period of initial high flow (4.4 L.min(-1)). We recorded values for
      blood pressure, heart rate, peripheral O2 saturation, inspiratory isoflurane,
      expiratory isoflurane, inspiratory O2, expiratory O2, inspiratory N2O, expiratory
      N2O, inspiratory CO2, CO2 concentration after expiration, Minimum Alveolar
      Concentration. In addition, we determined the total consumption rate of fentanyl,
      dexmedetomidine and isoflurane as well as bleeding. RESULTS: In each group the
      heart rate decreased after dexmedetomidine loading. After intubation, values were
      higher for Group A at one, three, five, 10, and 15 minutes. After intubation, the
      patients reached desired hypotension values at minute five for Group N and at
      minute 20 for group A. MAC values were higher for Group N at minute one, three,
      five, 10, and 15 (p < 0.05). FiO2 values were high between minute five and 60 for
      Group A, while at minute 90 Group N values were higher (p < 0.05). Fi Iso
      (inspiratuvar isofluran) values were lower in Group N at minute 15 and 30 (p <
      0.05). CONCLUSION: By using dexmedetomidine instead of nitrous oxide in low flow
      isoflurane anesthesia, we attained desired MAP levels, sufficient anesthesia
      depth, hemodynamic stability and safe inspiration parameters. Dexmedetomidine
      infusion with medical air-oxygen as a carrier gas represents an alternative
      anesthetic technique.

PMID- 24565118
TI  - Transcriptional control of HIV latency: cellular signaling pathways, epigenetics,
      happenstance and the hope for a cure.
AB  - Replication-competent latent HIV-1 proviruses that persist in the genomes of a
      very small subset of resting memory T cells in infected individuals under life
      long antiretroviral therapy present a major barrier towards viral eradication.
      Multiple molecular mechanisms are required to repress the viral trans-activating
      factor Tat and disrupt the regulatory Tat feedback circuit leading to the
      establishment of the latent viral reservoir. In particular, latency is due to a
      combination of transcriptional silencing of proviruses via host epigenetic
      mechanisms and restrictions on the expression of P-TEFb, an essential co-factor
      for Tat. Induction of latent proviruses in the presence of antiretroviral therapy
      is expected to enable clearance of latently infected cells by viral cytopathic
      effects and host antiviral immune responses. An in-depth comprehensive
      understanding of the molecular control of HIV-1 transcription should inform the
      development of optimal combinatorial reactivation strategies that are intended to
      purge the latent viral reservoir. 

PMID- 24565123
TI  - Assessment of the effect of ketamine in combination with remifentanil on
      postoperative pain.
AB  - BACKGROUND AND OBJECTIVES: The combination of ketamine and remifentanil seems to
      be associated with better analgesia and duration. The aim of this study was to
      evaluate whether a ketamine- remifentanil combination promotes improved
      postoperative analgesia. METHODS: Prospective, randomized, double blind study of
      40 patients undergoing video laparoscopic cholecystectomy. Anesthesia was
      performed with remifentanil, propofol, atracurium, and 50% oxygen. Group 1 (GI)
      patients received remifentanil (0.4 mcg.kg(-1).min(-1)) and ketamine (5 mcg.kg(
      1).min(-1)) and Group 2 (G2) received remifentanil (0.4 mcg.kg(-1).min(-1)) and
      saline solution. Morphine 0.1 mg.kg(-1) was administered at the end of the
      procedure, and postoperative pain was treated with morphine via PCA. We evaluated
      the severity of postoperative pain by a numerical scale from zero to 10 during 24
      hours. We registered the time to the first analgesic supplementation, amount of
      morphine used in the first 24 hours, and adverse effects. RESULTS: There was a
      decrease in pain severity between extubation and other times evaluated in G1 and
      G2. There was no significant difference in pain intensity between the groups.
      There was no difference between G1 (22 +/- 24.9 min) and G2 (21.5 +/- 28.1 min)
      regarding time to first dose of morphine and dose supplement of morphine consumed
      in G1 (29 +/- 18.4 mg) and G2 (25.1 +/- 13.3 mg). CONCLUSION: The combination of
      ketamine (5 mcg.kg(-1).min(-1)) and remifentanil (0.4 mcg.kg(-1).min(-1)) for
      cholecystectomy did not alter the severity of postoperative pain, time to first
      analgesic supplementation or dose of morphine in 24 hours.

PMID- 24565124
TI  - Anti-nociceptive, analgesic and pathohistological effects of intrathecal
      dexmedetomidine and bupivacaine in rats.
AB  - BACKGROUND AND OBJECTIVES: This study investigates analgesic and nociceptive
      effects of adding dexmedetomidine to bupivacaine neuraxial anesthesia through
      Tail-flick (TF) and Hot-plate (HP) tests and the pathohistological changes on
      spinal nerves and nerve roots through light microscopy. METHODS: Forty
      anesthetized, male Sprague-Dawley rats were intrathecally catheterized. Basal
      values of TF and HP tests were measured before and after catheterization. Thirty
      six successfully catheterized rats were assigned to four groups. Group B received
      10 MUg bupivacaine, Group BD3 received 10 MUg bupivacaine + 3 MUg
      dexmedetomidine, Group BD10 received 10 MUg bupivacaine + 10 MUg dexmedetomidine
      and Control group received 10 MUL volume of artificial cerebrospinal fluid. TF
      and HP tests were performed between the 5(th) and 300(th) minutes of drug
      administration. Twenty-four hours after administration of drugs, rats were
      sacrificed and spinal cord and nerve roots were removed for pathological
      investigation. RESULTS: Baseline values of the TF and HP tests were not
      statistically different among the groups (6.8 +/- 0.15 s). TF and HP latencies in
      the Control group did not change significantly during the study. TF and HP test
      results showed that adding 3 and 10 MUg dexmedetomidine caused a dose- dependent
      increase in duration and amplitude of analgesic and nociceptive effect of
      bupivacaine (TF: 37.52 +/- 1.08%, 57.86 +/- 1.16% respectively, HP: 44.24 +/-
      1.15%, 68.43 +/- 1.24% respectively). CONCLUSIONS: There were no apparent
      pathohistological changes at least 24 hours after the intrathecal administration
      of a single dose of dexmedetomidine 3 MUg and 10 MUg. Dexmedetomidine added to
      bupivacaine for spinal block improves analgesia and prolongs block duration.

PMID- 24565125
TI  - Reinsertion of the stylet does not affect incidence of Post Dural Puncture
      Headaches (PDPH) after spinal anesthesia.
AB  - BACKGROUND AND OBJECTIVES: This study was conducted to investigate the effects of
      reinsertion of the stylet after a spinal anesthesia procedure on the Post Dural
      Puncture Headache (PDPH) METHODS: We have enrolled into this study 630 patients
      who were undergoing elective operations with spinal anesthesia and randomized
      them to Group A (stylet replacement before needle removal) and Group B (needle
      removal without stylet replacement). These patients were observed for the
      duration of 24 hours in the hospital and they were checked for PDPH on the 3(rd)
      and the 7(th) day of the study. RESULTS: Overall, the PDPH incidence was at 10.8%
      (68 patients). Thirty-three of these patients (10.5%) who were in Group A (stylet
      replacement before needle removal) and the other 35 patients (11.1%) who were in
      Group B (needle removal without stylet replacement) experienced PDPH. There was
      no significant difference between the two groups with respect to the PDPH.
      CONCLUSIONS: In contrary to the diagnostic lumbar puncture, reinsertion of the
      stylet after spinal anesthesia with 25-gauge Quincke needles does not reduce the
      incidence of PDPH.

PMID- 24565126
TI  - Relevance of routine testing in low-risk patients undergoing minor and medium
      surgical procedures.
AB  - BACKGROUND AND OBJECTIVES: Preoperative tests aim to reduce morbidity and
      mortality of surgical patients, cost of perioperative care, and preoperative
      anxiety. Clinical evaluation allows defining the need for additional tests and
      strategies to reduce the surgical-anesthetic risk. The aim of this study was to
      evaluate the benefit of routine preoperative testing of low-risk patients
      undergoing minor and medium surgical procedures. METHODS: A descriptive cross
      sectional study of 800 patients seen at the preanesthetic assessment department
      of Hospital Santo Antonio, Salvador, BA. Patients with physical status ASA I,
      aged 1-45 years and scheduled to undergo elective minor and medium surgeries were
      include in the study. We evaluated changes in blood count, coagulation profile,
      electrocardiogram, chest X-ray, blood sugar, kidney function, sodium and
      potassium levels, and eventual change in clinical approach occurring due to these
      changes. RESULTS: Of 800 patients evaluated, a blood count was performed in
      97.5%, coagulation in 89%t, electrocardiogram in 74.1%, chest X-ray in 62%,
      fasting glucose in 68%, serum urea and creatinine in 55.7%, and plasma levels of
      sodium and potassium in 10.1%. Of these 700 patients, 68 (9.71%) showed changes
      in preoperative routine tests and only 10 (14.7%) of the patients with abnormal
      tests had a preoperative modified approach (i.e., new tests ordered, referral to
      a specialist or surgery postponement). No surgery was suspended. CONCLUSION: We
      found that preoperative additional tests are excessively ordered, even for young
      patients with low surgical risk, with little or no interference in perioperative
      management. Laboratory tests, besides generating high and unnecessary costs, are
      not good standardized screening instruments for diseases.

PMID- 24565127
TI  - The effect of levobupivacaine and bupivacaine on QT, corrected QT (Qtc), and P
      wave dispersions in cesarean section.
AB  - BACKGROUND AND OBJECTIVES: In our study we aimed to investigate the effect of
      bupivacaine and levobupivacaine on QT, corrected QT (QTc), and P wave dispersion
      durations during spinal anesthesia in cesarean section. METHODS: Sixty
      parturients scheduled for elective cesarean section in ASA I-II risk groups were
      included in the study. Baseline electrocardiographic (ECG) records of the
      patients were obtained in the operation room. Heart rate (HR), non-invasive blood
      pressure (NIBP), peripheral oxygen saturation (SpO2) and respiration rates (RR)
      were recorded. Venous cannulation was performed with 18G cannula and fluid
      preload made with 10 mL.kg(-1). Lactated Ringer solution. After fluid preload,
      second ECG recordings were taken and the patients were randomly separated into
      two groups. Group B (n = 30) received 10mg of bupivacaine and Group L (n = 30)
      received 10mg of levobupivacaine for spinal anesthesia. ECG recordings were
      repeated at 1, 5 and 10 minutes after spinal block. HR, NIBP, SpO2, RR and
      sensory block levels were also recorded at the same time intervals. At
      predetermined time intervals of spinal anesthesia, P wave dispersion (Pwd), QT
      dispersion (QTd), and QTc dispersion (QTcd) durations were measured from ECG
      records. QT and QTc durations are calculated with Bazzett formula. RESULTS: There
      was no difference between two groups according to block levels, hemodynamic
      parameters, Pwd, QTd, QTc and QTcd durations. CONCLUSION: Bupivacaine and
      levobupivacaine may be preferred in spinal anesthesia in pregnant patients who
      have extended Pwd and QTcd preoperatively.

PMID- 24565128
TI  - The effect of head rotation on intraocular pressure in prone position: a
      randomized trial.
AB  - BACKGROUND AND OBJECTIVES: The increased intraocular pressure (IOP) - which
      decreases perfusion pressure on the optic nerve - increases by prone positioning
      (1). The aim of our study was to compare the effect of head rotation 45 degrees 
      laterally in prone position on the increase in IOP of upper placed and lower
      placed eyes in patients undergoing percutaneous nephrolithotomy (PCNL). METHODS:
      Forty-five patients were randomly divided into 2 Groups. IOP of the patients were
      recorded bilaterally in supine position before the operation had started.
      Patients were turned to prone position. The head was placed on a prone headrest
      without external direct compression to both eyes. Patients in Group I were kept
      in strictly neutral prone position where as patients in Group II were placed
      prone with their heads rotated 45 degrees  laterally to the right side. At the
      end of the operation, patients were turned to supine position and their IOP was
      measured immediately. RESULTS: There was no difference related to demographics,
      duration of surgery, blood loss and fluid input data. IOP values after surgery in
      prone position increased significantly compared to preoperative values in both
      groups (p < 0.05). After surgery in prone position IOP values of the upper
      positioned eyes in Group II were significantly lower than Group I and lower
      positioned eyes in Group II (p < 0.05). CONCLUSION: prone positioning increases
      IOP. In patients with prone position with a head rotation of 45 degrees 
      laterally, IOP in the upper positioned eye was significantly lower.

PMID- 24565129
TI  - Comparison of intravenous morphine, epidural morphine with/without bupivacaine or
      ropivacaine in postthoracotomy pain management with patient controlled analgesia
      technique.
AB  - BACKGROUND AND OBJECTIVES: The aim of this randomized, double-blinded,
      prospective study was to determine the effectiveness and side effects of
      intravenous or epidural use of morphine, bupivacaine or ropivacaine on post
      thoracotomy pain management. METHODS: Sixty patients undergoing elective
      thoracotomy procedure were randomly allocated into 4 groups by the sealed
      envelope technique. Group IVM, EM, EMB and EMR received patient controlled
      intravenous morphine, and epidural morphine, morphine-bupivacaine and morphine
      ropivacaine, respectively. Perioperative heart rate, blood pressure and oxygen
      saturation and postoperative pain at rest and during cough, side effects and
      rescue analgesic requirements were recorded at the 30(th) and 60(th) minutes and
      the 2(nd), 4(th), 6(th), 12(th), 24(th), 36(th), 48(th), and 72(nd) hour.
      RESULTS: Diclofenac sodium requirement during the study was lower in Group EM.
      Area under VAS-time curve was lower in Group EM compared to Group IVM, but
      similar to Group EMB and EMR. Pain scores at rest were higher at the 12, 24, 36,
      and 48(th) hour in Group IVM compared to Group EM. Pain scores at rest were
      higher at the 30(th) and 60(th) minutes in Group EM and Group IVM compared to
      Group EMB. Pain scores during cough at the 30(th) minute were higher in Group EM
      compared to Group EMB. There was no difference between Group IVM and Group EMR.
      CONCLUSIONS: Morphine used at the epidural route was found more effective than
      the intravenous route. While Group EM was more effective in the late period of
      postoperative, Group EMB was more effective in the early period. We concluded
      that epidural morphine was the most effective and preferred one.

PMID- 24565130
TI  - Anesthetic management of a pediatric patient with leigh syndrome.
AB  - BACKGROUND AND OBJECTIVES: Leigh syndrome (LS) is a rare disease caused by
      abnormalities of mitochondrial energy generation. The central nervous system is
      most frequently affected, with psychomotor underdevelopment, seizures, nystagmus,
      ophthalmoparesis, optic atrophy, ataxia, dystonia, or respiratory failure.
      Surgical and anesthetic procedures stimulate the tracheal irritability, and could
      exacerbate risks of aspiration, wheezing, breathing difficulties, gasping,
      hypoventilation, and apnea. CASE REPORT: We present the anesthetic management for
      a six-year-old boy with severe form of LS, involving repair of a femur fracture.
      Propofol and remifentanil were infused for general anesthesia. The patient was
      closely monitored during anesthesia and in the intensive care unit in the early
      postoperative period. CONCLUSIONS: Close intraoperative monitoring of patients,
      including invasive arterial blood pressure monitoring and frequently measuring
      the levels of blood gases, glucose, and lactate, made this procedure run
      smoothly. Intensive care and breathing support for the patient with LS, under
      sedation with an analgesic combination during the early postoperative period,
      minimized the stress response due to pain after surgery.

PMID- 24565131
TI  - Anesthetic approach of pregnant woman with cerebral arteriovenous malformation
      and subarachnoid hemorrhage during pregnancy: Case report.
AB  - BACKGROUND AND OBJECTIVES: Subarachnoid hemorrhage (SAH) during pregnancy is a
      rare event, and about half the cases are due to arteriovenous malformations
      (AVM). The authors describe the anesthetic approach of a 39 week pregnant patient
      scheduled for cesarean section, with a history of SAH due to AVM at 22 week
      gestation. CASE REPORT: 39 week pregnant patient, healthy prior to pregnancy,
      with a history of SAH at 22 week gestation, manifested by headache, vomiting, and
      dizziness without loss of consciousness or other deficits on admission to the
      emergency room. Magnetic resonance imaging (MRI) revealed a left frontal AVM.
      After a short hospital stay for stabilization and diagnosis, the final medical
      decision was to maintain the pregnancy and a multidisciplinary follow-up by
      neurosurgery and high-risk obstetric consultation. An elective cesarean section
      was performed at 39 weeks under epidural anesthesia. During the intraoperative
      period, an episode of hypotension rapidly reversed with phenylephrine occurred.
      The newborn Apgar score was 10/10. An epidural catheter was used for
      postoperative analgesia, also uneventful. CONCLUSIONS: There are very few
      published cases of anesthetic approach for pregnant women with symptomatic AVM.
      All decisions made by the multidisciplinary team, from choosing to continue the
      pregnancy to the ideal time for AVM intervention and type of anesthesia and
      analgesia, were weighted according to the risk of brain damage. Regarding the
      anesthetic procedure, the authors emphasize the need for hemodynamic stability.

PMID- 24565132
TI  - Occupational hazards and diseases related to the practice of anesthesiology.
AB  - BACKGROUND AND OBJECTIVES: The practice of anesthesiology is not without risks to
      the anesthesiologist. The operating room (OR), in which anesthesiologists spend
      most of their time, is regarded as an unhealthy workplace due to the potential
      risks it offers. In this review, we propose an analysis of the occupational
      hazards that anesthesiologists are exposed in their daily practice. CONTENT: We
      present a classification of risk and its relationship to occupational diseases.
      CONCLUSION: Control of occupational hazards to which anesthesiologists are
      exposed daily is necessary in order to develop an appropriate workplace and
      minimize risks to the good practice of anesthesiology. This contributes to
      decrease absenteeism, improve patients' care and quality of life of
      anesthesiologists.

PMID- 24565134
TI  - cGRNB: a web server for building combinatorial gene regulatory networks through
      integrated engineering of seed-matching sequence information and gene expression
      datasets.
AB  - BACKGROUND: We are witnessing rapid progress in the development of methodologies
      for building the combinatorial gene regulatory networks involving both TFs
      (Transcription Factors) and miRNAs (microRNAs). There are a few tools available
      to do these jobs but most of them are not easy to use and not accessible online.
      A web server is especially needed in order to allow users to upload experimental
      expression datasets and build combinatorial regulatory networks corresponding to
      their particular contexts. METHODS: In this work, we compiled putative TF-gene,
      miRNA-gene and TF-miRNA regulatory relationships from forward-engineering
      pipelines and curated them as built-in data libraries. We streamlined the R codes
      of our two separate forward-and-reverse engineering algorithms for combinatorial
      gene regulatory network construction and formalized them as two major functional
      modules. As a result, we released the cGRNB (combinatorial Gene Regulatory
      Networks Builder): a web server for constructing combinatorial gene regulatory
      networks through integrated engineering of seed-matching sequence information and
      gene expression datasets. The cGRNB enables two major network-building modules,
      one for MPGE (miRNA-perturbed gene expression) datasets and the other for
      parallel miRNA/mRNA expression datasets. A miRNA-centered two-layer combinatorial
      regulatory cascade is the output of the first module and a comprehensive genome
      wide network involving all three types of combinatorial regulations (TF-gene, TF
      miRNA, and miRNA-gene) are the output of the second module. CONCLUSIONS: In this
      article we propose cGRNB, a web server for building combinatorial gene regulatory
      networks through integrated engineering of seed-matching sequence information and
      gene expression datasets. Since parallel miRNA/mRNA expression datasets are
      rapidly accumulated by the advance of next-generation sequencing techniques,
      cGRNB will be very useful tool for researchers to build combinatorial gene
      regulatory networks based on expression datasets. The cGRNB web-server is free
      and available online at http://www.scbit.org/cgrnb.

PMID- 24565135
TI  - Do flexible alcohol trading hours reduce violence? A theory-based natural
      experiment in alcohol policy.
AB  - Alcohol-related violence is a pressing public health concern. In 2005, the
      government of England and Wales took a controversial approach to preventing
      violence by removing restrictions on opening hours for alcohol outlets, thus
      increasing the availability of alcohol. The policy aimed to remove fixed closing
      times, which it claimed was contributing to urban violence occurring at peak
      closing times. It proposed to reduce violence and disorder by installing systems
      of 'staggered closing times'. This policy was criticised for overlooking
      established public health principles prioritising the control of alcohol
      availability in the prevention of alcohol-related harm. In this study, we treated
      the removal of trading hour restrictions as a natural experiment to test
      competing theoretical principles about the relationship between alcohol
      availability and violence. Our study took place in the City of Manchester over a
      four-year period 2004-2008. Detailed trading records for over 600 alcohol outlets
      were obtained, as were police records for all violent incidents. We found
      considerable variation in the implementation of extended trading hours across the
      city, which affected area-level exposure of changes in alcohol availability and
      staggered closing times. To isolate the effect of these changes on violence, we
      performed a dose-response analysis to examine whether improved staggering of
      closing hours (or increased alcohol availability) was associated with decreases
      in violence. We found no evidence to support the government-proposed hypothesis
      that staggered closing reduces violence. We also found no support for the
      alternative hypothesis; that increase alcohol availability would result in
      increased violence. This study provides an example of how better evidence can be
      generated from natural experiments by placing added emphasis on theory, causal
      mechanisms and implementation science. 

PMID- 24565133
TI  - SNAI1 is critical for the aggressiveness of prostate cancer cells with low E
      cadherin.
AB  - BACKGROUND: A better molecular understanding of prostate carcinogenesis is
      warranted to devise novel targeted preventive and therapeutic strategies against
      prostate cancer (PCA), a major cause of mortality among men. Here, we examined
      the role of two epithelial-to-mesenchymal transition (EMT) regulators, the
      adherens junction protein E-cadherin and its transcriptional repressor SNAI1, in
      regulating the aggressiveness of PCA cells. METHODS: The growth rate of human
      prostate carcinoma PC3 cells with stable knock-down of E-cadherin (ShEC-PC3) and
      respective control cells (Sh-PC3) was compared in MTT and clonogenic assays in
      cell culture and in nude mouse xenograft model in vivo. Stemness of ShEC-PC3 and
      Sh-PC3 cells was analyzed in prostasphere assay. Western blotting and
      immunohistochemistry (IHC) were used to study protein expression changes
      following E-cadherin and SNAI1 knock-down. Small interfering RNA (siRNA)
      technique was employed to knock- down SNAI1 protein expression in ShEC-PC3 cells.
      RESULTS: ShEC-PC3 cells exerted higher proliferation rate both in cell culture
      and in athymic nude mice compared to Sh-PC3 cells. ShEC-PC3 cells also formed
      larger and a significantly higher number of prostaspheres suggesting an increase
      in the stem cell-like population with E-cadherin knock-down. Also, ShEC-PC3
      prostaspheres disintegration, in the presence of serum and attachment, generated
      a bigger mass of proliferating cells as compared to Sh-PC3 prostaspheres.
      Immunoblotting/IHC analyses showed that E-cadherin knock-down increases the
      expression of regulators/biomarkers for stemness (CD44, cleaved Notch1 and Egr-1)
      and EMT (Vimentin, pSrc-tyr416, Integrin beta3, beta-catenin, and NF-kappaB) in
      cell culture and xenograft tissues. The expression of several bone metastasis
      related molecules namely CXCR4, uPA, RANKL and RunX2 was also increased in ShEC
      PC3 cells. Importantly, we observed a remarkable increase in SNAI1 expression in
      cytoplasmic and nuclear fractions, prostaspheres and xenograft tissues of ShEC
      PC3 cells. Furthermore, SNAI1 knock-down by specific siRNA strongly inhibited the
      prostasphere formation, clonogenicity and invasiveness, and decreased the level
      of pSrc-tyr416, total Src and CD44 in ShEC-PC3 cells. Characterization of RWPE-1,
      WPE1-NA22, WPE1-NB14 and DU-145 cells further confirmed that low E-cadherin is
      associated with higher SNAI1 expression and prostasphere formation. CONCLUSIONS:
      Together, these results suggest that E-cadherin loss promotes SNAI1 expression
      that controls the aggressiveness of PCA cells.

PMID- 24565136
TI  - Mobilising "vulnerability" in the public health response to pandemic influenza.
AB  - Analysis of public health's growing interest in "vulnerability" has largely
      focused on health policy, with little interrogation of how vulnerability is being
      actively appropriated, countered, ignored or reworked by the publics whose health
      such policy is designed to protect. Once the assemblage of public health is
      understood as comprised of different forms of expertise and actors, including
      publics, addressing this gap matters. We examine the use of vulnerability in the
      specific context of pandemic influenza preparedness. Pandemic preparedness raises
      some familiar dilemmas for public health governance: how to engage with publics
      without fuelling social divisions and disruption; and whether to invoke publics
      as passive recipients of public health advice or to recognise publics as
      collective agents responding to the threat of pandemic influenza. Thus, we ask
      how the mobilisation of vulnerability connects with these dilemmas. To examine
      vulnerability in pandemic preparedness, two forms of qualitative data are
      analysed: 1) interviews and focus groups with "vulnerable" and "healthy" people
      (conducted 2011-12) discussing seasonal and pandemic influenza and; 2)
      international, Australian national and state level pandemic plans (1999-2013).
      Vulnerability is variously used in plans as a way to identify groups at
      particular risk of infection because of pre-existing clinical conditions, and as
      a free-floating social category that could apply to a broad range of people
      potentially involved in the social disruption a pandemic might entail. Our
      interview and focus group data indicate that healthy people rework the free
      floating extension of vulnerability, and that people designated vulnerable
      encounter an absence of any collective responsibility for the threat of pandemic
      influenza. Our analysis suggests that vulnerability's mobilisation in pandemic
      preparedness limits the connection between public health governance and its
      publics: here, the openness and unpredictability of people's collective agency is
      something to be tightly controlled by a government concerned with protecting
      people from themselves. 

PMID- 24565137
TI  - The spread of 'Post Abortion Syndrome' as social diagnosis.
AB  - This paper examines the content of Post Abortion Syndrome (PAS) claims, the
      social actors involved and how this social diagnosis bypassed professional
      dissent and diffused into public policy in the United States. Previous works on
      the spread of PAS focus on almost exclusively on anti-abortion think tanks and
      policymakers. Missing from these analyses, however, is an emphasis on the
      grassroots-level actions undertaken by evangelical crisis pregnancy center (CPC)
      activists in introducing and circulating PAS claims. The CPC movement introduced
      PAS claims and provided the fodder for anti-abortion think tanks to construct
      evidence of pro-life claims. Despite dissent from health professionals and
      academic researchers, CPC PAS claims successfully diffused into federal and state
      abortion policy. I draw upon Brown et al.'s social diagnosis framework and
      Armstrong's five-stage model of diagnosis development to frame this account. 

PMID- 24565138
TI  - Perceived Organizational Justice in Care Services: creation and multi-sample
      validation of a measure.
AB  - Organizational justice (OJ) perceptions predict attitudes and behaviors of
      customers and employees across a broad range of services. Although OJ has proven
      predictive power and relevance, it has rarely been studied in health care
      settings. This stems partially from the lack of a reliable and valid measure of
      patients' OJ in health care encounters. The objective here was to create and
      validate a measure of patients' OJ. With that purpose, a survey study with two
      sampling contexts - the U.S. and Spain - was carried out in order to provide a
      cross-national validation of the scale in two versions: English (Perceived
      Organizational Justice in Care Services, PJustCS) and Spanish (Percepcion de
      Justicia Organizacional en el Ambito Sanitario, PJustAS). Exploratory Factor
      Analysis (EFA) and Confirmatory Factor Analysis (CFA) were used to select the
      appropriate items in the final version of the instrument. Reliability and
      validity of the measure were tested. A total of 406 patients in the U.S. and 473
      patients in Spain participated. The measures used were the newly created scale of
      Perceived Organizational Justice in Care Services (PJustCS/PJustAS) and scales of
      patients' Satisfaction, Trust and Global Justice. Factor Analyses supported the
      four dimensional structure of the instrument for each group. Multigroup CFA
      substantiated invariant factor loadings and invariant structural models across
      both samples, hence, supporting that the instrument is applicable in its two
      versions: English and Spanish. Validation results showed expected positive
      relations of OJ with patients' satisfaction, trust in clinicians and global
      perceived justice. These results point out the importance of health care
      customers' perceived organizational justice in the explanation of health care
      dynamics. The scale has desirable psychometric properties and shows adequate
      validity, contributing to the potential development of the area. 

PMID- 24565139
TI  - Socioeconomic status and the incidence of child injuries in China.
AB  - Injuries are the major cause of morbidity among children and one of the leading
      causes of death for children ages 1-17 years in developing countries. Of
      particular importance is whether child injuries are equally distributed across
      all socioeconomic groups and the implications of this question for child injury
      prevention, but there is a lack of research on the relationship between
      socioeconomic status and risk of child injuries in developing countries,
      including China. This study used a provincially-representative, population-based
      sample of 98,385 Chinese children under age 18 to investigate the relationships
      between socioeconomic status (SES) and child injuries. Despite the lack of a SES
      gradient in the overall incidence of nonhospitalized injuries, evidence of SES
      disparity was found for the overall incidence of H/PD injuries (injuries
      resulting in hospitalization or permanent disability) and fatal injuries. The
      odds of getting injured in the poorest wealth quintile were about 1.3 and 3.5
      times greater than the odds found in the richest wealth quintile for H/PD and
      fatal injuries respectively. Further analyses showed that the associations
      between SES and injuries varied by type and severity of injury, and across
      different life stages. The findings have important implications for identifying
      at-risk populations and the optimal times for interventions to reduce different
      types and severity levels of child injuries. 

PMID- 24565140
TI  - Healthy migrant and salmon bias hypotheses: a study of health and internal
      migration in China.
AB  - The existing literature has often underscored the "healthy migrant" effect and
      the "salmon bias" in understanding the health of migrants. Nevertheless, direct
      evidence for these two hypotheses, particularly the "salmon bias," is limited.
      Using data from a national longitudinal survey conducted between 2003 and 2007 in
      China, we provide tests of these hypotheses in the case of internal migration in
      China. To examine the healthy migrant effect, we study how pre-migration self
      reported health is associated with an individual's decision to migrate and the
      distance of migration. To test the salmon bias hypothesis, we compare the self
      reported health of migrants who stay in destinations and who return or move
      closer to home villages. The results provide support for both hypotheses.
      Specifically, healthier individuals are more likely to migrate and to move
      further away from home. Among migrants, those with poorer health are more likely
      to return or to move closer to their origin communities. 

PMID- 24565141
TI  - Treatment seeking and health financing in selected poor urban neighbourhoods in
      India, Indonesia and Thailand.
AB  - This article presents a comparative analysis of socio-economic disparities in
      relation to treatment-seeking strategies and healthcare expenditures in poor
      neighbourhoods within larger health systems in four cities in India, Indonesia
      and Thailand. About 200 households in New Delhi, Bhubaneswar, Jogjakarta and
      Phitsanulok were repeatedly interviewed over 12 months to relate health problems
      with health seeking and health financing at household level. Quantitative data
      were complemented with ethnographic studies involving the same neighbourhoods and
      a number of private practitioners at each site. Within each site, the higher and
      lower income groups among the poor were compared. The lower income group was more
      likely than the higher income group to seek care from less qualified health
      providers and incur catastrophic health spending. The study recommends linking
      quality control mechanisms with universal health coverage (UHC) policies; to
      monitor the impact of UHC among the poorest; intervention research to reach the
      poorest with UHC; and inclusion of private providers without formal medical
      qualification in basic healthcare. 

PMID- 24565142
TI  - Health capabilities and diabetes self-management: the impact of economic, social,
      and cultural resources.
AB  - While the "social determinants of health" view compels us to explore how social
      structures shape health outcomes, it often ignores the role individual agency
      plays. In contrast, approaches that focus on individual choice and personal
      responsibility for health often overlook the influence of social structures.
      Amartya Sen's "capabilities" framework and its derivative the "health
      capabilities" (HC) approach attempts to accommodate both points of view,
      acknowledging that individuals function under social conditions over which they
      have little control, while also acting as agents in their own health and well
      being. This paper explores how economic, social, and cultural resources shape the
      health capability of people with diabetes, focusing specifically on dietary
      practices. Health capability and agency are central to dietary practices, while
      also being shaped by immediate and broader social conditions that can generate
      habits and a lifestyle that constrain dietary behaviors. From January 2011 to
      December 2012, we interviewed 45 people with diabetes from a primary care clinic
      in Ontario (Canada) to examine how their economic, social, and cultural resources
      combine to influence dietary practices relative to their condition. We classified
      respondents into low, medium, and high resource groups based on economic
      circumstances, and compared how economic resources, social relationships, health
      related knowledge and values combine to enhance or weaken health capability and
      dietary management. Economic, social, and cultural resources conspired to
      undermine dietary management among most in the low resource group, whereas social
      influences significantly influenced diet among many in the medium group. High
      resource respondents appeared most motivated to maintain a healthy diet, and also
      had the social and cultural resources to enable them to do so. Understanding the
      influence of all three types of resources is critical for constructing ways to
      enhance health capability, chronic disease self-management, and health. 

PMID- 24565144
TI  - Caregiving intensity and retirement status in Canada.
AB  - A number of OECD countries have implemented policies encouraging longer labour
      force participation in tandem with policies encouraging informal care provision
      in the community. To better understand how these policies may affect the
      available pool of caregivers and labour force participants, we need more evidence
      about how informal caregiving is related to retirement status and timing. We
      assessed the association between caregiving intensity and retirement status for
      individuals aged 55 to 69 using the Canadian 2007 General Social Survey, a cross
      sectional survey with 23,404 individuals. We used multinomial logistic
      regressions to determine whether providing different intensities of informal care
      (i.e. hours of weekly care) was significantly associated with the likelihood that
      an individual was fully retired, had retired and returned to work, had never
      retired and was working part-time or full-time, or was a labour market non
      participant. We found that higher intensity caregiving was associated with being
      fully retired (relative to working full-time) for men and women (relative risk
      ratios, 2.93 and 2.04, respectively). For women, high intensity caregiving was
      also associated with working part-time (1.84) and being a labour force non
      participant (1.99). Male and female high intensity caregivers were more likely to
      be retired before age 65. Our results highlight the importance of measuring
      caregiving intensity and multiple paths to retirement, which are often overlooked
      in the caregiving and retirement literature. They also indicate that a policy
      context encouraging both later retirement and more informal care may not be
      reasonable without flexible work arrangement options. 

PMID- 24565143
TI  - Pricing schemes for new drugs: a welfare analysis.
AB  - Drug price regulation is acquiring increasing significance in the investment
      choices of the pharmaceutical sector. The overall objective is to determine an
      optimal trade-off between the incentives for innovation, consumer protection, and
      value for money. However, price regulation is itself a source of distortion. In
      this study, we examine the welfare properties of listing through a bargaining
      process and value-based pricing schemes. The latter are superior instruments to
      uncertain listing processes for maximising total welfare, but the distribution of
      the benefits between consumers and the industry depends on rate of rebate chosen
      by the regulator. However, through an appropriate choice, it is always possible
      to define a value-based pricing scheme with risk sharing, which both consumers
      and the industry prefer to an uncertain bargaining process. 

PMID- 24565145
TI  - Quality of life instruments for economic evaluations in health and social care
      for older people: a systematic review.
AB  - Gaining health may not be the main goal of healthcare services aimed at older
      people, which may (also) seek to improve wellbeing. This emphasizes the need of
      finding appropriate outcome measures for economic evaluation of such services,
      particularly in long-term care, capturing more than only health-related quality
      of life (HrQol). This review assesses the usefulness of HrQol and wellbeing
      instruments for economic evaluations specifically aimed at older people, focusing
      on generic and preference-based questionnaires measuring wellbeing in particular.
      We systematically searched six databases and extracted instruments used to assess
      HrQol and wellbeing outcomes. Instruments were compared based on their usefulness
      for economic evaluation of services aimed at older people (dimensions measured,
      availability of utility scores, extent of validation). We identified 487 articles
      using 34 generic instruments: 22 wellbeing (two of which were preference-based)
      and 11 HrQol instruments. While standard HrQol instruments measure physical,
      social and psychological dimensions, wellbeing instruments contain additional
      dimensions such as purpose in life and achievement, security, and freedom. We
      found four promising wellbeing instruments for inclusion in economic evaluation:
      Ferrans and Powers QLI and the WHO-Qol OLD, ICECAP-O and the ASCOT. Ferrans and
      Powers QLI and the WHO-Qol OLD are widely validated but lack preference-weights
      while for ICECAP-O and the ASCOT preference-weights are available, but are less
      widely validated. Until preference-weights are available for the first two
      instruments, the ICECAP-O and the ASCOT currently appear to be the most useful
      instruments for economic evaluations in services aimed at older people. Their
      limitations are that (1) health dimensions may be captured only partially and (2)
      the instruments require further validation. Therefore, we currently recommend
      using the ICECAP-O or the ASCOT alongside the EQ-5D or SF-6D when evaluating
      interventions aimed at older people. 

PMID- 24565146
TI  - The interaction of family background and personal education on depressive
      symptoms in later life.
AB  - This study assesses the interaction between personal education and family
      background during childhood on depressive symptoms in later life by applying Ross
      & Mirowsky's resource substitution and structural amplification theory of health
      and education. OLS regression models are estimated using data from the "Survey of
      Health, Ageing and Retirement in Europe" (SHARE), which covers information on
      current social and health status as well as retrospective life histories from
      20,716 respondents aged 50 or older from thirteen European countries. Higher
      education helps to overcome the negative consequences of a poor family
      background. Since people from poor families are less likely to attain higher
      educational levels, they lack exactly the resource they need in order to overcome
      the negative consequences their non-prosperous background has on depressive
      symptoms. Thus, low family background and low personal education amplify each
      other. Examining the processes described by theory of resource substitution and
      structural amplification over different age groups from midlife to old-age
      suggests that the moderating effect of education remains constant over age among
      people coming from a poor family background. However, there is some evidence for
      a decrease with age in the buffering effect of a well-off family background on
      depressive symptoms among the low educated group. Furthermore, the educational
      gap in depression diverges with age among individuals originating from a well-off
      family background. Taken together the results cautiously allude to the conclusion
      that three processes - cumulative (dis-)advantage, age-as-leveler, and persistent
      inequalities - might take place. 

PMID- 24565147
TI  - Can mobile phones help control neglected tropical diseases? Experiences from
      Tanzania.
AB  - The increasing proliferation of mobiles offers possibilities for improving health
      systems in developing countries. A case in point is Tanzania which has piloted a
      mobile phone-based Management Information System (MIS) for the control of
      neglected tropical diseases (NTDs) where village health workers (VHWs) were given
      mobile phones with web-based software to test the feasibility of using frontline
      health workers to capture data at point of source. Based on qualitative case
      study research carried out in 2011, we found that providing mobile phones to VHWs
      has helped to increase the efficiency of routine work boosting the motivation and
      self-esteem of VHWs. However, despite these advantages, the information generated
      from the mobile phone-based NTD MIS has yet to be used to support decentralised
      decision-making. Even with improved technology and political will, the biggest
      hindrance to local usage of information for health planning is the lack of
      synthesised and analysed health information from the district and national levels
      to the villages. Without inculcating a culture of providing health information
      feedback to frontline workers and community organisations, the benefits of the
      intervention will be limited. If not addressed, this will mean that mobiles have
      maintained the one-way upward flow of information for NTD control and simply made
      reporting more hi-tech. 

PMID- 24565149
TI  - Selling patients and other metaphors: a discourse analysis of the interpretive
      frames that shape emergency department admission handoffs.
AB  - This paper reports a discourse analysis of the language doctors used as they
      talked about and engaged in patient handoffs between the emergency department
      (ED) and various inpatient services at one highly specialized academic tertiary
      teaching and referral hospital in the Midwest United States. Although interest in
      handoff improvement has grown considerably in recent years, progress has been
      hampered, perhaps in part, because of a widely used but limiting conceptual model
      of handoff as an information transmission. The purpose of the study reported here
      is to analyze the way doctors make sense of handoff interactions, including
      uncovering the interpretive frames they use, in order to provide empirical
      findings to expand conceptual models of handoff. All data reported were drawn
      from a two-year ethnographic study (2009-2011) and include semi-structured
      interviews (n = 48), non-participant observations (349 h), and recorded telephone
      handoff conversations (n = 48). A total of eighty-six individuals participated,
      including resident and attending doctors from the ED, internal medicine and
      surgical services, as well as hospital administrators. Findings are organized
      around four metaphors doctors used: sales, sports and games, packaging, and
      teamwork. Each metaphor, in turn, reveals an underlying interpretive frame that
      appears to be influenced by organizational and social structures and to shape the
      possibilities for action that doctors perceive. The four underlying interpretive
      frames are: handoff as persuasion, handoff as competition, handoff as expectation
      matching, and handoff as collaboration. Taken together, these interpretive frames
      highlight the complex, socially interactive nature of handoff and provide an
      empirical basis for grounding and enriching the conceptual model of handoff that
      guides research and practice improvement efforts. 

PMID- 24565148
TI  - Informal caregivers' hopes and expectations of a referral to a memory clinic.
AB  - Although only 20-50% of individuals with dementia are diagnosed, early diagnosis
      enables patients and families to access interventions and services, and plan for
      the future. The current study explored the experiences of rural family caregivers
      in the period leading up to a diagnostic assessment at a Canadian memory clinic,
      their hopes and expectations of the assessment, and their experiences in the six
      months following diagnosis. Using a longitudinal, retrospective and prospective
      qualitative research design, caregivers of 30 patients referred to the clinic
      were interviewed during the diagnostic assessment process and again six months
      after the diagnosis. Most caregivers reported first noticing symptoms two years
      prior to diagnosis. The pre-diagnostic interviews revealed a prevalent 'need to
      know' among caregivers that drove the help-seeking process. Caregivers hoped that
      the diagnosis would have the benefits of 'naming it,' 'accessing treatment,'
      'knowing what to expect,' and 'receiving guidance.' When asked six months later
      about the impact of the diagnosis, the main theme was 'acceptance and moving
      forward.' Caregivers reported that the diagnosis provided 'relief,' 'validation,'
      and 'improved access to services.' These findings can inform care practices of
      primary health care providers who represent the first point of contact regarding
      expectations and experiences of dementia-related diagnoses. 

PMID- 24565151
TI  - Governing healthcare: finding meaning in a clinical practice guideline for the
      management of non-specific low back pain.
AB  - Clinical practice guidelines produced by NICE - the National Institute for Health
      and Care Excellence - are seen as key mechanisms to regulate and standardise UK
      healthcare practice, but their development is known to be problematic, and their
      adoption and uptake variable. Examining what a guideline or health policy means
      to different audiences, and how it means something to those communities, provides
      new insight about interpretive discourses. In this paper we present a micro
      analysis of the response of healthcare professionals to publication of a single
      NICE guideline in 2009 which proposed a re-organisation of professional services
      for chronic non-specific low back pain. Adopting an interpretive approach, we
      seek to understand both the meaning of the guideline and the socio-political
      events associated with it. Drawing on archived policy documents related to the
      development and publication of the guideline, texts published in professional
      journals and on web-sites, and semi-structured interview data from professionals
      associated with the debate, we identify a key discourse that positions the
      management of chronic non-specific low back pain within physician jurisdiction.
      We examine the emergence of this discourse through policy-related symbolic
      artifacts taking the form of specific languages, objects and acts. This discourse
      effectively resisted and displaced the service reorganisation proposed by the
      guideline and, in so doing, ensured medical hegemony within practice and
      professional organisations concerned with the management of non-specific low back
      pain. 

PMID- 24565150
TI  - Does change in the neighborhood environment prevent obesity in older women?
AB  - Neighborhood environment is consistently associated with obesity; changes to
      modifiable aspects of the neighborhood environment may curb the growth of obesity
      in the US and other developed nations. However, currently the majority of studies
      are cross-sectional and thus not appropriate for evaluating causality. The goal
      of this study was to evaluate the effect of a neighborhood-changing intervention
      on changes in obesity among older women. Over the past 30 years the Portland,
      Oregon metropolitan region has made significant investments in plans, regulatory
      structures, and public facilities to reduce sprawl and increase compact growth
      centers, transit-oriented development approaches, and green space. We used
      geocoded residential addresses to link data on land-use mix, public transit
      access, street connectivity, and access to green space from four time points
      between 1986 and 2004, with longitudinal data on body mass index (BMI) from a
      cohort of 2003 community-dwelling women aged 66 years and older. Height and
      weight were measured at clinic visits. Women self-reported demographics, health
      habits, and chronic conditions, and self-rated their health. Neighborhood
      socioeconomic status was assessed from census data. Neighborhood walkability and
      access to green space improved over the 18-year study period. On average there
      was a non-significant mean weight loss in the cohort between baseline (mean age
      72.6 years) and the study's end (mean age 85.0 years). We observed no association
      between neighborhood built environment or change in built environment and BMI.
      Greater neighborhood socioeconomic status at baseline was independently
      associated with a healthier BMI at baseline, and protected against an age-related
      decline in BMI over time. BMI decreases with age reflect increased frailty,
      especially among older adults with complex morbidities. Future research should
      consider the influence of the neighborhood environment on additional relevant
      health outcomes and should include measures of the social environment in
      conjunction with built environment measures. 

PMID- 24565152
TI  - "She mixes her business": HIV transmission and acquisition risks among female
      migrants in western Kenya.
AB  - Migration and HIV research in sub-Saharan Africa has focused on HIV risks to male
      migrants, yet women's levels of participation in internal migration have met or
      exceeded those of men in the region. Moreover, studies that have examined HIV
      risks to female migrants found higher risk behavior and HIV prevalence among
      migrant compared to non-migrant women. However, little is known about the
      pathways through which participation in migration leads to higher risk behavior
      in women. This study aimed to characterize the contexts and processes that may
      facilitate HIV acquisition and transmission among migrant women in the Kisumu
      area of Nyanza Province, Kenya. We used qualitative methods, including 6 months
      of participant observation in women's common migration destinations and in-depth
      semi-structured interviews conducted with 15 male and 40 female migrants selected
      from these destinations. Gendered aspects of the migration process may be linked
      to the high risks of HIV observed in female migrants - in the circumstances that
      trigger migration, livelihood strategies available to female migrants, and social
      features of migration destinations. Migrations were often precipitated by
      household shocks due to changes in marital status (as when widowhood resulted in
      disinheritance) and gender-based violence. Many migrants engaged in transactional
      sex, of varying regularity, from clandestine to overt, to supplement earnings
      from informal sector trading. Migrant women are at high risk of HIV transmission
      and acquisition: the circumstances that drove migration may have also increased
      HIV infection risk at origin; and social contexts in destinations facilitate
      having multiple sexual partners and engaging in transactional sex. We propose a
      model for understanding the pathways through which migration contributes to HIV
      risks in women in high HIV prevalence areas in Africa, highlighting potential
      opportunities for primary and secondary HIV prevention at origins and
      destinations, and at key 'moments of vulnerability' in the migration process. 

PMID- 24565153
TI  - Implications for alcohol minimum unit pricing advocacy: what can we learn for
      public health from UK newsprint coverage of key claim-makers in the policy
      debate?
AB  - On May 24th 2012, Scotland passed the Alcohol (Minimum Pricing) Bill. Minimum
      unit pricing (MUP) is an intervention that raises the price of the cheapest
      alcohol to reduce alcohol consumption and related harms. There is a growing
      literature on industry's influence in policymaking and media representations of
      policies, but relatively little about frames used by key claim-makers in the
      public MUP policy debate. This study elucidates the dynamic interplay between key
      claim-makers to identify lessons for policy advocacy in the media in the UK and
      internationally. Content analysis was conducted on 262 articles from seven UK and
      three Scottish national newspapers between 1st May 2011 and 31st May 2012,
      retrieved from electronic databases. Advocates' and critics' constructions of the
      alcohol problem and MUP were examined. Advocates depicted the problem as
      primarily driven by cheap alcohol and marketing, while critics' constructions
      focused on youth binge drinkers and dependent drinkers. Advocates justified
      support by citing the intervention's targeted design, but critics denounced the
      policy as illegal, likely to encourage illicit trade, unsupported by evidence and
      likely to be ineffective, while harming the responsible majority, low-income
      consumers and businesses. Critics' arguments were consistent over time, and
      single statements often encompassed multiple rationales. This study presents
      advocates with several important lessons for promoting policies in the media.
      Firstly, it may be useful to shift focus away from young binge drinkers and heavy
      drinkers, towards population-level over-consumption. Secondly, advocates might
      focus on presenting the policy as part of a wider package of alcohol policies.
      Thirdly, emphasis on the success of recent public health policies could help
      portray the UK and Scotland as world leaders in tackling culturally embedded
      health and social problems through policy; highlighting past successes when
      presenting future policies may be a valuable tactic both within the UK and
      internationally. 

PMID- 24565155
TI  - Income inequality and sexually transmitted in the United States: who bears the
      burden?
AB  - Three causal processes have been proposed to explain associations between group
      income inequality and individual health outcomes, each of which implies health
      effects for different segments of the population. We present a novel conceptual
      and analytic framework for the quantitative evaluation of these pathways,
      assessing the contribution of: (i) absolute deprivation - affecting the poor in
      all settings - using family income; (ii) structural inequality - affecting all
      those in unequal settings - using the Gini coefficient; and (iii) relative
      deprivation - affecting only the poor in unequal settings - using the Yitzhaki
      index. We conceptualize relative deprivation as the interaction of absolute
      deprivation and structural inequality. We test our approach using hierarchical
      models of 11,183 individuals in the National Longitudinal Study of Adolescent
      Health (Add Health). We examine the relationship between school-level inequality
      and sexually transmitted infections (STI) - self-reported or laboratory-confirmed
      Chlamydia, Gonorrhoea or Trichomoniasis. Results suggest that increased poverty
      and inequality were both independently associated with STI diagnosis, and that
      being poor in an unequal community imposed an additional risk. However, the
      effects of inequality and relative deprivation were confounded by individuals'
      race/ethnicity. 

PMID- 24565154
TI  - Understanding motives for intravaginal practices amongst Tanzanian and Ugandan
      women at high risk of HIV infection: the embodiment of social and cultural norms
      and well-being.
AB  - Some types of intravaginal practices (IVP) may increase the risk for HIV
      acquisition. This is particularly worrisome for populations with dual high
      prevalence of HIV and IVP. Women involved in transactional sex are at increased
      risk for HIV infection in sub-Saharan Africa. Social, cultural and economic
      influences are strong drivers of IVP in this population. To explore this, we
      carried out a qualitative research study to investigate the drivers and
      motivations for using IVP within a large observational study of women at high
      risk of HIV in Tanzania and Uganda from September 2008 to September 2009. Of the
      201 women selected, 176 women took part in a semi-structured in-depth interview.
      Additionally, in Tanzania, eight focus group discussions among study participants
      and community members were carried out to obtain information on community norms
      and expectations. IVP were motivated by overlapping concerns with hygiene,
      morality, sexual pleasure, fertility, relationship security, and economic
      security. These motives were driven by the need to meet cultural and social
      expectations of womanhood, and at the same time attend to personal well-being.
      Among women involved in transactional sex in East Africa, interventions aimed at
      modifying or eliminating IVP should attend to local cultural and social norms as
      well as the individual as an agent of change. 

PMID- 24565156
TI  - Assessing the population-level impact of vouchers on access to health facility
      delivery for women in Kenya.
AB  - Although available evidence indicates that vouchers improve service utilization
      among the target populations, we do not know whether increased utilization
      results from improved access (new clients who would not have used services
      without the voucher) or from shifting clients from non-accredited to contracted
      service providers. This paper examines whether the safe motherhood voucher
      program in Kenya is associated with improved access to health facility delivery
      using information on births within two years preceding the survey in voucher and
      comparison sites. Data were collected in 2010-2011 and in 2012 among 2933 and
      3094 women aged 15-49 years reporting 962 and 1494 births within two years before
      the respective surveys. Analysis entails cross-tabulations and estimation of
      multilevel random-intercept logit models. The results show that the proportion of
      births occurring at home declined by more than 10 percentage points while the
      proportion of births delivered in health facilities increased by a similar margin
      over time in voucher sites. The increase in facility-based births occurred in
      both public and private health facilities. There was also a significant increase
      in the likelihood of facility-based delivery (odds ratios [OR]: 2.04; 95%
      confidence interval [CI]: 1.40-2.98 in the 2006 voucher arm; OR: 1.72; 95% CI:
      1.22-2.43 in the 2010-2011 voucher arm) in voucher sites over time. In contrast,
      there were no significant changes in the likelihood of facility-based delivery in
      the comparison arm over time. These findings suggest that the voucher program
      contributed to improved access to institutional delivery by shifting births from
      home to health facilities. However, available evidence from qualitative data
      shows that some women who purchased the vouchers did not use them because of high
      transportation costs to accredited facilities. The implication is that
      substantial improvements in service uptake could be achieved if the program
      subsidized transportation costs as well. 

PMID- 24565157
TI  - Health sector priority setting at meso-level in lower and middle income
      countries: lessons learned, available options and suggested steps.
AB  - Setting priority for health programming and budget allocation is an important
      issue, but there is little consensus on related processes. It is particularly
      relevant in low resource settings and at province- and district- or "meso-level",
      where contextual influences may be greater, information scarce and capacity
      lower. Although recent changes in disease epidemiology and health financing
      suggest even greater need to allocate resources effectively, the literature is
      relatively silent on evidence-based priority-setting in low and middle income
      countries (LMICs). We conducted a comprehensive review of the peer-reviewed and
      grey literature on health resource priority-setting in LMICs, focussing on meso
      level and the evidence-based priority-setting processes (PSPs) piloted or
      suggested there. Our objective was to assess PSPs according to whether they have
      influenced resource allocation and impacted the outcome indicators prioritised.
      An exhaustive search of the peer-reviewed and grey literature published in the
      last decade yielded 57 background articles and 75 reports related to priority
      setting at meso-level in LMICs. Although proponents of certain PSPs still
      advocate their use, other experts instead suggest broader elements to guide
      priority-setting. We conclude that currently no process can be confidently
      recommended for such settings. We also assessed the common reasons for failure at
      all levels of priority-setting and concluded further that local authorities
      should additionally consider contextual and systems limitations likely to prevent
      a satisfactory process and outcomes, particularly at meso-level. Recent
      literature proposes a list of related attributes and warning signs, and
      facilitated our preparation of a simple decision-tree or roadmap to help
      determine whether or not health systems issues should be improved in parallel to
      support for needed priority-setting; what elements of the PSP need improving;
      monitoring, and evaluation. Health priority-setting at meso-level in LMICs can
      involve common processes, but will often require additional attention to local
      health systems. 

PMID- 24565160
TI  - Structure fragmentation in Fe-based alloys by means of cyclic martensitic
      transformations of different types.
AB  - The effect of martensite transformations of different types on the misorientation
      of austenite crystalline lattice, which characterizes the degree of structure
      fragmentation, was investigated for Fe-Ni and Fe-Mn alloys. As a result of
      multiple face-centered cubic (f.c.c.)-body-centered cubic (b.c.c.)-f.c.c.
      transformations, an austenite single-crystalline specimen is transformed in a
      polycrystalline one due to progressive fragmentation. It was shown that the
      degree of fragmentation depends on the magnitude of volume change and the density
      of dislocations generated on martensitic transformations. 

PMID- 24565158
TI  - Elucidating the ensemble of functionally-relevant transitions in protein systems
      with a robotics-inspired method.
AB  - BACKGROUND: Many proteins tune their biological function by transitioning between
      different functional states, effectively acting as dynamic molecular machines.
      Detailed structural characterization of transition trajectories is central to
      understanding the relationship between protein dynamics and function.
      Computational approaches that build on the Molecular Dynamics framework are in
      principle able to model transition trajectories at great detail but also at
      considerable computational cost. Methods that delay consideration of dynamics and
      focus instead on elucidating energetically-credible conformational paths
      connecting two functionally-relevant structures provide a complementary approach.
      Effective sampling-based path planning methods originating in robotics have been
      recently proposed to produce conformational paths. These methods largely model
      short peptides or address large proteins by simplifying conformational space.
      METHODS: We propose a robotics-inspired method that connects two given structures
      of a protein by sampling conformational paths. The method focuses on small- to
      medium-size proteins, efficiently modeling structural deformations through the
      use of the molecular fragment replacement technique. In particular, the method
      grows a tree in conformational space rooted at the start structure, steering the
      tree to a goal region defined around the goal structure. We investigate various
      bias schemes over a progress coordinate for balance between coverage of
      conformational space and progress towards the goal. A geometric projection layer
      promotes path diversity. A reactive temperature scheme allows sampling of rare
      paths that cross energy barriers. RESULTS AND CONCLUSIONS: Experiments are
      conducted on small- to medium-size proteins of length up to 214 amino acids and
      with multiple known functionally-relevant states, some of which are more than 13A
      apart of each-other. Analysis reveals that the method effectively obtains
      conformational paths connecting structural states that are significantly
      different. A detailed analysis on the depth and breadth of the tree suggests that
      a soft global bias over the progress coordinate enhances sampling and results in
      higher path diversity. The explicit geometric projection layer that biases the
      exploration away from over-sampled regions further increases coverage, often
      improving proximity to the goal by forcing the exploration to find new paths. The
      reactive temperature scheme is shown effective in increasing path diversity,
      particularly in difficult structural transitions with known high-energy barriers.

PMID- 24565159
TI  - Shrinkage regression-based methods for microarray missing value imputation.
AB  - BACKGROUND: Missing values commonly occur in the microarray data, which usually
      contain more than 5% missing values with up to 90% of genes affected. Inaccurate
      missing value estimation results in reducing the power of downstream microarray
      data analyses. Many types of methods have been developed to estimate missing
      values. Among them, the regression-based methods are very popular and have been
      shown to perform better than the other types of methods in many testing
      microarray datasets. RESULTS: To further improve the performances of the
      regression-based methods, we propose shrinkage regression-based methods. Our
      methods take the advantage of the correlation structure in the microarray data
      and select similar genes for the target gene by Pearson correlation coefficients.
      Besides, our methods incorporate the least squares principle, utilize a shrinkage
      estimation approach to adjust the coefficients of the regression model, and then
      use the new coefficients to estimate missing values. Simulation results show that
      the proposed methods provide more accurate missing value estimation in six
      testing microarray datasets than the existing regression-based methods do.
      CONCLUSIONS: Imputation of missing values is a very important aspect of
      microarray data analyses because most of the downstream analyses require a
      complete dataset. Therefore, exploring accurate and efficient methods for
      estimating missing values has become an essential issue. Since our proposed
      shrinkage regression-based methods can provide accurate missing value estimation,
      they are competitive alternatives to the existing regression-based methods.

PMID- 24565161
TI  - What are the key challenges we face in kidney transplantation today?
AB  - Transplantation is more predictable than it was 20 to 30 years ago and innovation
      over the last 20 years has been rapid, delivering substantial short-term and
      medium-term improvements. The challenges ahead are to deliver improved results
      globally in the context of also preventing chronic disease and reducing the costs
      of treatment. Countries achieving the best rates of transplantation combine
      deceased and living donors and can transplant more than 50 people per annum per
      million population, so why can this not be achieved everywhere? The mortality
      rates have dropped, but they are still up to 10-fold worse than age- and sex
      matched controls, such that transplantation ages individuals by 30 years in terms
      of mortality risk. Cardiovascular disease, infection and malignancy remain the
      targets if mortality is to normalize. Graft survival rates will not change until
      the multiple injuries constituting chronic allograft dysfunction and the problems
      of recurrent disease can be brought to heel. Biomarkers may provide the next
      innovation to advance outcomes, but early experimental tolerance protocols
      implemented in clinical practice in at least three centers may deliver results
      more quickly. 

PMID- 24565162
TI  - Detecting overlapping protein complexes in PPI networks based on robustness.
AB  - BACKGROUND: Recently, large data sets of protein-protein interactions (PPI) which
      can be modeled as PPI networks are generated through high-throughput methods. And
      locally dense regions in PPI networks are very likely to be protein complexes.
      Since protein complexes play a key role in many biological processes, detecting
      protein complexes in PPI networks is one of important tasks in post-genomic era.
      However, PPI networks are often incomplete and noisy, which builds barriers to
      mining protein complexes. RESULTS: We propose a new and effective algorithm based
      on robustness to detect overlapping clusters as protein complexes in PPI
      networks. And in order to improve the accuracy of resulting clusters, our
      algorithm tries to reduce bad effects brought by noise in PPI networks. And in
      our algorithm, each new cluster begins from a seed and is expanded through adding
      qualified nodes from the cluster's neighbourhood nodes. Besides, in our
      algorithm, a new distance measurement method between a cluster K and a node in
      the neighbours of K is proposed as well. The performance of our algorithm is
      evaluated by applying it on two PPI networks which are Gavin network and Database
      of Interacting Proteins (DIP). The results show that our algorithm is better than
      Markov clustering algorithm (MCL), Clique Percolation method (CPM) and core
      attachment based method (CoAch) in terms of F-measure, co-localization and Gene
      Ontology (GO) semantic similarity. CONCLUSIONS: Our algorithm detects locally
      dense regions or clusters as protein complexes. The results show that protein
      complexes generated by our algorithm have better quality than those generated by
      some previous classic methods. Therefore, our algorithm is effective and useful.

PMID- 24565163
TI  - The National Institutes of Health Microphysiological Systems Program focuses on a
      critical challenge in the drug discovery pipeline.
AB  - The National Institutes of Health has partnered with the US Food and Drug
      Administration and the Defense Advanced Research Projects Agency to accelerate
      the development of human microphysiological systems (MPS) that address challenges
      faced in predictive toxicity assessment and efficacy analysis of new molecular
      entities during the preclinical phase of drug development. Use of human MPS could
      provide better models for predicting the efficacy of new molecular entities in
      clinical trials. It is also anticipated that improvements in predicting drug
      toxicities early in the drug development process through the use of MPS or human
      organs-on-a-chip will decrease the need to withdraw new therapies from the market
      and minimize or eliminate deaths due to unidentified drug toxicities. 

PMID- 24565164
TI  - Diagnosis and treatment of dementia: the fourth canadian consensus conference.

PMID- 24565165
TI  - Genes associated with genotype-specific DNA methylation in squamous cell
      carcinoma as candidate drug targets.
AB  - BACKGROUND: Aberrant DNA methylation is often associated with cancers. Thus,
      screening genes with cancer-associated aberrant DNA methylation is a useful
      method to identify candidate cancer-causing genes. Aberrant DNA methylation is
      also genotype dependent. Thus, the selection of genes with genotype-specific
      aberrant DNA methylation in cancers is potentially important for tailor-made
      medicine. The selected genes are important candidate drug targets. RESULTS: The
      recently proposed principal component analysis based selection of genes with
      aberrant DNA methylation was applied to genotype and DNA methylation patterns in
      squamous cell carcinoma measured using single nucleotide polymorphism (SNP)
      arrays. SNPs that are frequently found in cancers are usually highly methylated,
      and the genes that were selected using this method were reported previously to be
      related to cancers. Thus, genes with genotype-specific DNA methylation patterns
      will be good therapeutic candidates. The tertiary structures of the proteins
      encoded by the selected genes were successfully inferred using two profile-based
      protein structure servers, FAMS and Phyre2. Candidate drugs for three of these
      proteins, tyrosine kinase receptor (ALK), EGLN3 protein, and NUAK family SNF1
      like kinase 1 (NUAK1), were identified by ChooseLD. CONCLUSIONS: We detected
      genes with genotype-specific DNA methylation in squamous cell carcinoma that are
      candidate drug targets. Using in silico drug discovery, we successfully
      identified several candidate drugs for the ALK, EGLN3 and NUAK1 genes that
      displayed genotype-specific DNA methylation.

PMID- 24565166
TI  - Are cryptic species a problem for parasitological biological tagging for stock
      identification of aquatic organisms?
AB  - The effective use of biological tags in stock assessment relies on the reliable
      identification of the parasites concerned. This may be compromised if cryptic
      species are not recognized. Here we review what is known about cryptic species in
      aquatic hosts and its potential importance in this respect. Although strictly
      cryptic species may be considered as species which can be distinguished only by
      molecular data, we accept the far looser but more practical definition of species
      that cannot be readily distinguished morphologically. Cryptic species appear to
      have been identified most frequently as occurring in separate host species; this
      is heartening in that this has no significant impact on tagging studies. But
      cryptic species have occasionally been identified in single hosts sympatrically
      and are relatively common in geographically distinct populations of the same host
      species. Ignorance of both kinds of occurrences has the capacity to undermine the
      reliability of tagging analysis. We review in detail what is known of intra- and
      interspecific genetic variation over geographical ranges in the trematodes, based
      on recent molecular studies. Although the existence of cryptic species and
      evidence of intraspecific variability may appear daunting, we suspect that these
      complexities will add, and indeed have already added, to the sophistication of
      the information that can be derived from tagging studies.

PMID- 24565167
TI  - Association between traumatic events and post-traumatic stress disorder: results
      from the ESEMeD-Spain study.
AB  - BACKGROUND: The relative importance of traumatic events (TEs) in accounting for
      the social burden of post-traumatic stress disorder (PTSD) could vary according
      to cross-cultural factors. In that sense, no such studies have yet been conducted
      in the Spanish general population. The present study aims to determine the
      epidemiology of trauma and PTSD in a Spanish community sample using the randomly
      selected TEs method. METHODS: The European Study of the Epidemiology of Mental
      Disorders (ESEMeD)-Spain is a cross-sectional household survey of a
      representative sample of adult population. Lifetime prevalence of self-reported
      TEs and lifetime and 12-month prevalence of PTSD were evaluated using the World
      Health Organization (WHO) Composite International Diagnostic Interview. Reports
      of PTSD associated with randomly selected TEs were weighted by the individual
      level probabilities of TE selection to generate estimates of population-level
      PTSD risk associated with each TE. RESULTS: Road accident was the most commonly
      self-reported TE (14.1%). Sexual assault had the highest conditional risk of PTSD
      (16.5%). The TEs that contributed most to societal PTSD burden were unexpected
      death of a loved one (36.4% of all cases) and sexual assault (17.2%). Being
      female and having a low educational level were associated with low risk of
      overall TE exposure and being previously married was related to higher risk.
      Being female was related to high risk of PTSD after experiencing a TE.
      CONCLUSIONS: Having an accident is commonly reported among Spanish adults, but
      two TE are responsible for the highest burden associated with PTSD: the
      unexpected death of someone close and sexual assault. These results can help
      designing public health interventions to reduce the societal PTSD burden.

PMID- 24565168
TI  - Slipping during side-step cutting: anticipatory effects and familiarization.
AB  - The aim of the present study was to verify whether the expectation of
      perturbations while performing side-step cutting manoeuvres influences lower limb
      EMG activity, heel kinematics and ground reaction forces. Eighteen healthy men
      performed two sets of 90 degrees  side-step cutting manoeuvres. In the first set,
      10 unperturbed trials (Base) were performed while stepping over a moveable force
      platform. In the second set, subjects were informed about the random possibility
      of perturbations to balance throughout 32 trials, of which eight were perturbed
      (Pert, 10cm translation triggered at initial contact), and the others were
      "catch" trials (Catch). Center of mass velocity (CoMVEL), heel acceleration
      (HAC), ground reaction forces (GRF) and surface electromyography (EMG) from lower
      limb and trunk muscles were recorded for each trial. Surface EMG was analyzed
      prior to initial contact (PRE), during load acceptance (LA) and propulsion (PRP)
      periods of the stance phase. In addition, hamstrings-quadriceps co-contraction
      ratios (CCR) were calculated for these time-windows. The results showed no
      changes in CoMVEL, HAC, peak GRF and surface EMG PRE among conditions. However,
      during LA, there were increases in tibialis anterior EMG (30-50%) concomitant to
      reduced EMG for quadriceps muscles, gluteus and rectus abdominis for Catch and
      Pert conditions (15-40%). In addition, quadriceps EMG was still reduced during
      PRP (p<.05). Consequently, CCR was greater for Catch and Pert in comparison to
      Base (p<.05). These results suggest that there is modulation of muscle activity
      towards anticipating potential instability in the lower limb joints and assure
      safety to complete the task. 

PMID- 24565169
TI  - Factors associated with one year retention to methadone maintenance treatment
      program among patients with heroin dependence in China.
AB  - OBJECTIVE: The aim of this study was to evaluate the risk factors associated with
      dropout from Methadone Maintenance Treatment (MMT) clinics within a 1 year follow
      up cohort study in China. METHODS: A data analysis is to explore the adherence of
      MMT during one year from three hundred and twenty patients with heroin dependence
      at five clinics (3 in Shanghai, 2 in Kunming) in China. All participants were
      from the part of China-United States cooperation project entitled "Research about
      improving the compliance and efficacy of methadone maintenance treatment in
      China". Our data analysis includes the patients' attendance in the 6 months
      clinical study and the data in another 6 months afterward. The data of patients
      at baseline were collected with the Addiction Severity Index (ASI) which is a
      semi-structured questionnaire covering socio-demographic characteristics and drug
      use history. The one year attendance after recruitment at the clinics and daily
      dose were abstracted from the MMT clinic register system. The Cox proportional
      hazards model were used to explore the risk factor of dropout, defined as seven
      consecutive days without methadone. RESULTS: By the end of 1 year of treatment 86
      patients still remained in MMT without dropout (87% in Shanghai and 13% patients
      in Kunming). Over the entire 1-year period the median days of remaining in the
      program were 84 days (in Shanghai and Kunming were 317 days and 22 days).The
      factors associated with retention included age (HR=0.98, 95%C.I.:0.96-0.99,
      P=0.0062) and ASI alcohol scores (HR=5.72, 95%C.I.:1.49-21.92, P=0.0109) at
      baseline. CONCLUSION: One year retention of newly recruited patients with heroin
      dependence was related to age and ASI alcohol scores at baseline. The adherence
      is poorer for the patients who are young and having more serious alcohol
      problems.

PMID- 24565170
TI  - Candidatus Neoehrlichia mikurensis and Anaplasma phagocytophilum in urban
      hedgehogs.

PMID- 24565172
TI  - A simple model for predicting aluminum bound phosphorus formation and internal
      loading reduction in lakes after aluminum addition to lake sediment.
AB  - The conversion of mobile phosphorus (P) to aluminum bound P (Al-P) after addition
      of Al to over 300 sub-samples from 35 sediment cores collected from 20 lakes in
      the upper Midwest, United States was investigated in this study. Consistent
      relationships between mobile P reduction and Al-P formation were detected across
      a broad range of mobile sediment P contents (0.04-2.8 g P m(-2) cm(-1) or 0.083
      2.8 mg P g(-1)DW) and lake types. The conversion of mobile P to Al-P was
      dependent on the initial mobile sediment P content and the amount of Al added to
      the sediment. An empirical model was then developed to predict the formation of
      Al-P based on the amount of Al added relative to the initial mass of mobile P in
      the sediment. The results were compared to sediment collected from an Al treated
      lake and good agreement was found between the model and in-situ changes to
      sediment P fractions caused by Al treatment. The model developed in this study,
      unlike previous models with extreme, singular endpoints, allows for a continuum
      of estimates for mobile P conversion to Al-P, along with efficiency of P binding
      by Al, as Al dose varies. Model results can be used in conjunction with mobile
      sediment P based predictions for internal P loading to calculate an Al dose
      required to meet internal phosphorus loading goals for lake management and
      restoration without the need for expensive, time consuming Al additions to
      sediment.

PMID- 24565171
TI  - Combination therapy with ampicillin and azithromycin in an experimental
      pneumococcal pneumonia is bactericidal and effective in down regulating
      inflammation in mice.
AB  - OBJECTIVES: Emergence of multidrug resistance among Streptococcus pneumoniae
      (SP), has limited the available options used to treat infections caused by this
      organism. The objective of this study was to compare the role of monotherapy and
      combination therapy with ampicillin (AMP) and azithromycin (AZM) in eradicating
      bacterial burden and down regulating lung inflammation in a murine experimental
      pneumococcal infection model. METHODS: Balb/C mice were infected with 106 CFU of
      SP. Treatments with intravenous ampicillin (200 mg/kg) and azithromycin (50
      mg/kg) either alone or in combination was initiated 18 h post infection, animals
      were sacrificed from 0 - 6 h after initiation of treatment. AMP and AZM were
      quantified in serum by microbiological assay. Levels of TNF-alpha, IFN-gamma IL
      6, and IL-10 in serum and in lungs, along with myeloperoxidase, inflammatory cell
      count in broncho alveolar lavage fluid, COX-2 and histopathological changes in
      lungs were estimated. RESULTS: Combination therapy down regulated lung
      inflammation and accelerated bacterial clearance. This approach also
      significantly decreased TNF-alpha, IFN-gamma, IL-6 and increased IL-10 level in
      serum and lungs along with decreased myeloperoxidase, pulmonary vascular
      permeability, inflammatory cell numbers and COX-2 levels in lungs. CONCLUSIONS:
      Combinatorial therapy resulted in comparable bactericidal activity against the
      multi-drug resistant isolate and may represent an alternative dosing strategy,
      which may help to alleviate problems with pneumococcal pneumonia.

PMID- 24565173
TI  - Against conventional wisdom: when the public, the media, and medical practice
      collide.
AB  - BACKGROUND: In 2009, the U.S. Preventive Services Task Force released new
      mammography screening guidelines that sparked a torrent of criticism. The
      subsequent conflict was significant and pitted the Task Force against other
      health organizations, advocacy groups, the media, and the public at large. We
      argue that this controversy was driven by the systematic removal of uncertainty
      from science communication. To increase comprehension and adherence, health
      information communicators remove caveats, limitations, and hedging so science
      appears simple and more certain. This streamlining process is, in many instances,
      initiated by researchers as they engage in dissemination of their findings, and
      it is facilitated by public relations professionals, journalists, public health
      practitioners, and others whose tasks involve using the results from research for
      specific purposes. ANALYSIS: Uncertainty is removed from public communication
      because many communicators believe that it is difficult for people to process
      and/or that it is something the audience wants to avoid. Uncertainty management
      theory posits that people can find meaning and value in uncertainty. We define
      key terms relevant to uncertainty management, describe research on the processing
      of uncertainty, identify directions for future research, and offer
      recommendations for scientists, practitioners, and media professionals confronted
      with uncertain findings. CONCLUSIONS: Science is routinely simplified as it is
      prepared for public consumption. In line with the model of information overload,
      this practice may increase short-term adherence to recommendations at the expense
      of long-term message consistency and trust in science.

PMID- 24565174
TI  - A scalable method for discovering significant subnetworks.
AB  - BACKGROUND: Study of biological networks is an essential first step to understand
      the complex functions they govern in different organisms. The topology of
      interactions that define how biological networks operate is often determined
      through high-throughput experiments. Noisy nature of high-throughput experiments,
      however, can result in multiple alternative network topologies that explain this
      data equally well. One key step to resolve the differences is to identify the
      subnetworks which appear significantly more frequently in a biological network
      data set than expected. METHOD: We present a method named SiS (Significant
      Subnetworks) to find subnetworks with the largest probability to appear in a
      collection of biological networks. We define these subnetworks as the most
      probable subnetworks. SiS summarizes the interactions in the given collection of
      networks in a special template network. It uses the template network to guide the
      search for most probable subnetworks. It computes the lower and upper bound
      scores on how good the potential solutions are (i.e., the number of input
      networks that contain the subnetwork). As the search continues, it tightens the
      bound dynamically and prunes a massive number of unpromising solutions in that
      process. RESULTS AND CONCLUSIONS: Experiments on comprehensive data sets depict
      that the most probable subnetworks found by SiS in a large collection of networks
      are also very frequent as well. In metabolic network data set, we found that
      subnetworks in eukaryote are more conserved than those of prokaryote. SiS also
      scales well to large data sets and subnetworks and runs orders of magnitude
      faster than an existing method, MULE. Depending on the size of the subnetwork in
      the same data set, the running time of SiS ranges from a few seconds to minutes;
      MULE, on the other hand, runs either for hours or does not even finish in days.
      In human transcription regulatory network data set, SiS finds a large backbone
      subnetwork that appears frequently regardless of diverse cell types.

PMID- 24565175
TI  - Unbiased, scalable sampling of protein loop conformations from probabilistic
      priors.
AB  - BACKGROUND: Protein loops are flexible structures that are intimately tied to
      function, but understanding loop motion and generating loop conformation
      ensembles remain significant computational challenges. Discrete search techniques
      scale poorly to large loops, optimization and molecular dynamics techniques are
      prone to local minima, and inverse kinematics techniques can only incorporate
      structural preferences in adhoc fashion. This paper presents Sub-Loop Inverse
      Kinematics Monte Carlo (SLIKMC), a new Markov chain Monte Carlo algorithm for
      generating conformations of closed loops according to experimentally available,
      heterogeneous structural preferences. RESULTS: Our simulation experiments
      demonstrate that the method computes high-scoring conformations of large loops
      (>10 residues) orders of magnitude faster than standard Monte Carlo and discrete
      search techniques. Two new developments contribute to the scalability of the new
      method. First, structural preferences are specified via a probabilistic graphical
      model (PGM) that links conformation variables, spatial variables (e.g., atom
      positions), constraints and prior information in a unified framework. The method
      uses a sparse PGM that exploits locality of interactions between atoms and
      residues. Second, a novel method for sampling sub-loops is developed to generate
      statistically unbiased samples of probability densities restricted by loop
      closure constraints. CONCLUSION: Numerical experiments confirm that SLIKMC
      generates conformation ensembles that are statistically consistent with specified
      structural preferences. Protein conformations with 100+ residues are sampled on
      standard PC hardware in seconds. Application to proteins involved in ion-binding
      demonstrate its potential as a tool for loop ensemble generation and missing
      structure completion.

PMID- 24565178
TI  - The effects of a reminder of underwater trauma on behaviour and memory-related
      mechanisms in the rat dentate gyrus.
AB  - Intrusive re-experiencing is a core symptom in post-traumatic stress disorder
      (PTSD), often triggered by contextual cues associated with the trauma. It is not
      yet clear if intrusive re-experiencing is only the result, or whether it may
      contribute to the establishment of PTSD following acute stress. This study aimed
      at examining the impact of an underwater trauma (UWT) reminder on anxiety-like
      behaviour and on neuronal activity and plasticity in the hippocampus and the
      amygdala. Sprague-Dawley rats were exposed to UWT and 24 h later were re-exposed
      to the context. The effects on behaviour, activation of the amygdala (BLA) and
      dentate gyrus (DG), and on long-term potentiation (LTP) and local circuit
      activity (frequency-dependent inhibition (FDI) and paired-pulse inhibition (PPI))
      in the DG were assessed. The exposure to UWT by itself resulted in increased
      anxiety behaviour in the open field, together with increased PPI. Upon exposure
      to the UWT reminder, an additional increase in anxiety was also observed in the
      EPM and in FDI. Moreover, reminder exposure resulted in impaired DG LTP and a
      significant BLA extracellular-signal-regulated kinases (ERK) 2 activation. In
      conclusion, these observed effects of exposure to a trauma reminder, following
      the exposure to the initial trauma, might be associated with the progression of
      trauma-related pathologies and the development of related disorders. 

PMID- 24565177
TI  - ppiPre: predicting protein-protein interactions by combining heterogeneous
      features.
AB  - BACKGROUND: Protein-protein interactions (PPIs) are crucial in cellular
      processes. Since the current biological experimental techniques are time
      consuming and expensive, and the results suffer from the problems of
      incompleteness and noise, developing computational methods and software tools to
      predict PPIs is necessary. Although several approaches have been proposed, the
      species supported are often limited and additional data like homologous
      interactions in other species, protein sequence and protein expression are often
      required. And predictive abilities of different features for different kinds of
      PPI data have not been studied. RESULTS: In this paper, we propose ppiPre, an
      open-source framework for PPI analysis and prediction using a combination of
      heterogeneous features including three GO-based semantic similarities, one KEGG
      based co-pathway similarity and three topology-based similarities. It supports up
      to twenty species. Only the original PPI data and gold-standard PPI data are
      required from users. The experiments on binary and co-complex gold-standard yeast
      PPI data sets show that there exist big differences among the predictive
      abilities of different features on different kinds of PPI data sets. And the
      prediction performance on the two data sets shows that ppiPre is capable of
      handling PPI data in different kinds and sizes. ppiPre is implemented in the R
      language and is freely available on the CRAN (http://cran.r
      project.org/web/packages/ppiPre/). CONCLUSIONS: We applied our framework to both
      binary and co-complex gold-standard PPI data sets. The detailed analysis on three
      GO aspects suggests that different GO aspects should be used on different kinds
      of data sets, and that combining all the three aspects of GO often gets the best
      result. The analysis also shows that using only features based solely on the
      topology of the PPI network can get a very good result when predicting the co
      complex PPI data. ppiPre provides useful functions for analysing PPI data and can
      be used to predict PPIs for multiple species.

PMID- 24565179
TI  - Building additional complexity to in vitro-derived intestinal tissues.
AB  - Gastrointestinal (GI) disorders affect up to 25% of the US population. Common
      intestinal disorders include malabsorption, irritable bowel syndrome and fecal
      incontinence. Some GI disorders such as Hirschsprung's disease have a genetic
      basis and are associated with an absence or paucity of enteric nerves. Current
      treatment plans for GI disorders range from changes in diet to bowel resection,
      and there are very few drugs available that target the primary deficiencies in
      intestinal function such as controlled peristalsis. While animal models can
      recapitulate the broad range of intestinal pathologies of the GI tract, they are
      intrinsically complicated and of low throughput. Several in vitro systems have
      been established, and these range from epithelial enteroids to more complex
      organoids, which contain most intestinal cell types. One of the more complex
      organoid systems was derived from adult mouse intestines and contains functional
      enteric nerves and smooth muscle capable of peristalsis. Establishing an
      equivalent human intestinal system is challenging due to limited access and
      variable quality of human intestinal tissues. However, owing to recent advances,
      it is possible to differentiate human induced and embryonic pluripotent stem
      cells, collectively called pluripotent stem cells, into human intestinal
      organoids (HIOs) in vitro. Although HIOs contain a significant degree of
      epithelial and mesenchymal complexity, they lack enteric nerves and thus are
      unable to model the peristaltic movements of the gut. The goal of this review is
      to discuss approaches to generate complex in vitro systems that can be used to
      more comprehensively model common intestinal pathologies. New and more
      biologically complete human models of the intestine would allow for unprecedented
      studies of the cellular and molecular basis of normal and pathological gut
      function. Furthermore, fully functional HIOs could serve as a platform for
      preclinical drug studies to model absorption and efficacy. 

PMID- 24565180
TI  - The effect of distance on observed mortality, childhood pneumonia and vaccine
      efficacy in rural Gambia.
AB  - We investigated whether straight-line distance from residential compounds to
      healthcare facilities influenced mortality, the incidence of pneumonia and
      vaccine efficacy against pneumonia in rural Gambia. Clinical surveillance for
      pneumonia was conducted on 6938 children living in the catchment areas of the two
      largest healthcare facilities. Deaths were monitored by three-monthly home
      visits. Children living >5 km from the two largest healthcare facilities had a
      2.78 [95% confidence interval (CI) 1.74-4.43] times higher risk of all-cause
      mortality compared to children living within 2 km of these facilities. The
      observed rate of clinical and radiological pneumonia was lower in children living
      >5 km from these facilities compared to those living within 2 km [rate ratios
      0.65 (95% CI 0.57-0.73) and 0.74 (95% CI 0.55-0.98), respectively]. There was no
      association between distance and estimated pneumococcal vaccine efficacy.
      Geographical access to healthcare services is an important determinant of
      survival and pneumonia in children in rural Gambia.

PMID- 24565182
TI  - The biaxial mechanical behaviour of abdominal aortic aneurysm intraluminal
      thrombus: classification of morphology and the determination of layer and region
      specific properties.
AB  - Intraluminal thrombus (ILT) is present in 75% of clinically-relevant abdominal
      aortic aneurysms (AAAs) yet, despite much research effort, its role in AAA
      biomechanics remains unclear. The aim of this work is to further evaluate the
      biomechanics of ILT and determine if different ILT morphologies have varying
      mechanical properties. Biaxial mechanical tests were performed on ILT samples
      harvested from 19 patients undergoing open surgical repair. ILT were separated
      into luminal, medial and medial/abluminal layers. A total of 356 tests were
      performed and the Cauchy stress (sigma) and tangential modulus (TM) at a stretch
      ratio (lambda) of 1.14 were recorded for each test in both the circumferential
      (theta) and longitudinal (L) directions. Our data revealed three distinct types
      of ILT morphologies, each with a unique set of mechanical properties. All ILT
      layers were found to be isotropic and inhomogeneous. Type 1 (n=10) was a multi
      layered ILT (thick medial/abluminal layer) whose strength and stiffness decreased
      gradually from the luminal to the medial/abluminal layer. Type 2 (n=6) was a
      multi-layered ILT (thin/highly degraded medial/abluminal layer) whose strength
      and stiffness decreased abruptly between the luminal and medial/abluminal layer
      and Type 3 (n=3) is a single layered ILT with a lower strength and stiffness than
      Types 1 and 2. In a sub-study, we found the luminal layer to be stronger and
      stiffer in the posterior than the anterior region. This work provides further
      insights to the biomechanical behaviour of ILT and the use of our ILT
      classification may be useful in future studies. 

PMID- 24565181
TI  - Detection of type 2 diabetes related modules and genes based on epigenetic
      networks.
AB  - BACKGROUND: Type 2 diabetes (T2D) is one of the most common chronic metabolic
      diseases characterized by insulin resistance and the decrease of insulin
      secretion. Genetic variation can only explain part of the heritability of T2D, so
      there need new methods to detect the susceptibility genes of the disease.
      Epigenetics could establish the interface between the environmental factor and
      the T2D Pathological mechanism. RESULTS: Based on the network theory and by
      combining epigenetic characteristics with human interactome, the weighted human
      DNA methylation network (WMPN) was constructed, and a T2D-related subnetwork
      (TMSN) was obtained through T2D-related differentially methylated genes. It is
      found that TMSN had a T2D specific network structure that non-fatal metabolic
      disease causing genes were often located in the topological and functional
      periphery of network. Combined with chromatin modifications, the weighted
      chromatin modification network (WCPN) was built, and a T2D-related chromatin
      modification pattern subnetwork was obtained by the TMSN gene set. TCSN had a
      densely connected network community, indicating that TMSN and TCSN could
      represent a collection of T2D-related epigenetic dysregulated sub-pathways. Using
      the cumulative hypergeometric test, 24 interplay modules of DNA methylation and
      chromatin modifications were identified. By the analysis of gene expression in
      human T2D islet tissue, it is found that there existed genes with the variant
      expression level caused by the aberrant DNA methylation and (or) chromatin
      modifications, which might affect and promote the development of T2D.
      CONCLUSIONS: Here we have detected the potential interplay modules of DNA
      methylation and chromatin modifications for T2D. The study of T2D epigenetic
      networks provides a new way for understanding the pathogenic mechanism of T2D
      caused by epigenetic disorders.

PMID- 24565183
TI  - Predicting human walking gaits with a simple planar model.
AB  - Models of human walking with moderate complexity have the potential to accurately
      capture both joint kinematics and whole body energetics, thereby offering more
      simultaneous information than very simple models and less computational cost than
      very complex models. This work examines four- and six-link planar biped models
      with knees and rigid circular feet. The two differ in that the six-link model
      includes ankle joints. Stable periodic walking gaits are generated for both
      models using a hybrid zero dynamics-based control approach. To establish a
      baseline of how well the models can approximate normal human walking, gaits were
      optimized to match experimental human walking data, ranging in speed from very
      slow to very fast. The six-link model well matched the experimental step length,
      speed, and mean absolute power, while the four-link model did not, indicating
      that ankle work is a critical element in human walking models of this type.
      Beyond simply matching human data, the six-link model can be used in an
      optimization framework to predict normal human walking using a torque-squared
      objective function. The model well predicted experimental step length, joint
      motions, and mean absolute power over the full range of speeds. 

PMID- 24565184
TI  - CNRS School "Nanophysics for Health", 5-9 November 2012, Mittelwhir, France.
      Preface.

PMID- 24565200
TI  - The influence of mTOR inhibitors on immunity and the relationship to post
      transplant malignancy.
AB  - The known role of mammalian target of rapamycin (mTOR) in the immune response has
      been rapidly evolving, from what was once thought to be a simple
      immunosuppressive antiproliferative effect on T cells to a very complex central
      role that serves to integrate multiple signals given to T cells, B cells and
      antigen-presenting cells. The complexity of this topic is demonstrated by recent
      data suggesting that mTOR inhibition can either inhibit or promote certain
      aspects of immune responses, depending on the nature of the antigenic stimulus,
      and the environmental conditions cueing the cellular immunological players. There
      is even evidence that, under mTOR inhibition, an immune response to one foreign
      entity (for example, an organ transplant) may be simultaneously completely
      different to that of another (for example, tumour or microorganism). To
      understand how this might be possible, it is necessary to investigate the central
      role that mTOR seems to have in shaping the immune response. This review is aimed
      at examining how mTOR controls the development and function of key immune cells,
      and puts this information primarily in the context of organ transplant rejection
      and post-transplant malignancy. 

PMID- 24565201
TI  - TiO2 micro-flowers composed of nanotubes and their application to dye-sensitized
      solar cells.
AB  - TiO2 micro-flowers were made to bloom on Ti foil by the anodic oxidation of Ti
      protruding dots with a cylindrical shape. Arrays of the Ti-protruding dots were
      prepared by photolithography, which consisted of coating the photoresists,
      attaching a patterned mask, illuminating with UV light, etching the Ti surface by
      reactive ion etching (RIE), and stripping the photoresist on the Ti foil. The
      procedure for the blooming of the TiO2 micro-flowers was analyzed by field
      emission scanning electron microscopy (FESEM) as the anodizing time was
      increased. Photoelectrodes of dye-sensitized solar cells (DSCs) were fabricated
      using TiO2 micro-flowers. Bare TiO2 nanotube arrays were used for reference
      samples. The short-circuit current (Jsc) and the power conversion efficiency of
      the DSCs based on the TiO2 micro-flowers were 4.340 mA/cm2 and 1.517%,
      respectively. These values of DSCs based on TiO2 micro-flowers were higher than
      those of bare samples. The TiO2 micro-flowers had a larger surface area for dye
      adsorption compared to bare TiO2 nanotube arrays, resulting in improved Jsc
      characteristics. The structure of the TiO2 micro-flowers allowed it to adsorb
      dyes very effectively, also demonstrating the potential to achieve higher power
      conversion efficiency levels for DSCs compared to a bare TiO2 nanotube array
      structure and the conventional TiO2 nanoparticle structure. 

PMID- 24565202
TI  - Loss of the putative tumor suppressor protein spinophilin is associated with poor
      prognosis in head and neck cancer.
AB  - The putative tumor suppressor protein spinophilin has been recently involved in
      the pathogenesis of lung, liver, and other types of cancer. Previous studies also
      indicate that a loss of spinophilin in combination with functional impairment of
      p53 drives tumor progression. To date, no data exist about the role of
      spinophilin in head and neck squamous cell carcinoma (HNSCC). In the present
      study, we evaluated spinophilin and p53 expression by immunohistochemistry in 85
      patients with nonmetastatic HNSCC. Kaplan-Meier curves and multivariate Cox
      proportional models were used to define the prognostic relevance of spinophilin
      for patients with HNSCC. Overall, immunoreactivity for spinophilin was reduced in
      40 tumors (47%). Nine cases (10.5%) showed complete loss of spinophilin. Kaplan
      Meier curve analysis demonstrated that reduced spinophilin expression is
      associated with poor overall survival (P = .022). Concomitant analysis of
      spinophilin and p53 further showed that patients with reduced spinophilin
      expression and nuclear p53 staining have a significantly decreased overall
      survival (hazard ratio, 1.96; 95% confidence interval, 1.06-3.61; P = .030). In
      conclusion, the combination of reduced spinophilin expression and nuclear p53
      staining indicates a poor prognosis in HNSCC patients. Based on our results,
      spinophilin might play a previously unrecognized role in the pathogenesis of
      HNSCC. 

PMID- 24565203
TI  - Automatic classification of white regions in liver biopsies by supervised machine
      learning.
AB  - Automated assessment of histological features of non-alcoholic fatty liver
      disease (NAFLD) may reduce human variability and provide continuous rather than
      semiquantitative measurement of these features. As part of a larger effort, we
      perform automatic classification of steatosis, the cardinal feature of NAFLD, and
      other regions that manifest as white in images of hematoxylin and eosin-stained
      liver biopsy sections. These regions include macrosteatosis, central veins,
      portal veins, portal arteries, sinusoids and bile ducts. Digital images of
      hematoxylin and eosin-stained slides of 47 liver biopsies from patients with
      normal liver histology (n = 20) and NAFLD (n = 27) were obtained at 20*
      magnification. The images were analyzed using supervised machine learning
      classifiers created from annotations provided by two expert pathologists. The
      classification algorithm performs with 89% overall accuracy. It identified
      macrosteatosis, bile ducts, portal veins and sinusoids with high precision and
      recall (>= 82%). Identification of central veins and portal arteries was less
      robust but still good. The accuracy of the classifier in identifying
      macrosteatosis is the best reported. The accurate automated identification of
      macrosteatosis achieved with this algorithm has useful clinical and research
      related applications. The accurate detection of liver microscopic anatomical
      landmarks may facilitate important subsequent tasks, such as localization of
      other histological lesions according to liver microscopic anatomy.

PMID- 24565204
TI  - Immunoglobulin class switching to IgG4 in Warthin tumor and analysis of serum
      IgG4 levels and IgG4-positive plasma cells in the tumor.
AB  - We previously reported a case of immunoglobulin (Ig)G4-related immune
      inflammation in Warthin tumor. Increased serum IgG4 levels and tissue
      infiltration of IgG4-positive plasma cells are characteristics of IgG4-related
      disease (IgG4-RD), a newly emerging clinicopathological entity. However, the
      relationship between IgG4-RD and Warthin tumor remains to be elucidated. We aimed
      to investigate the involvement of systemic and local IgG4 production and class
      switch recombination in Warthin tumor. We examined serum IgG4 levels and also
      analyzed the involvement of IgG4-positive plasma cells in Warthin tumors (18
      cases) compared with those of pleomorphic adenomas (19 cases) as controls.
      Furthermore, in specimens of Warthin tumors (3 cases), pleomorphic adenomas (2
      cases), and IgG4-RDs (2 cases), we examined messenger RNA expression of
      activation-induced cytidine deaminase, IgG4 germline transcripts and productive
      IgG4 by reverse transcription polymerase chain reaction. Serum IgG4 levels were
      increased in 5 of 18 Warthin tumors and not in any of the 19 pleomorphic
      adenomas. Infiltration of IgG4-positive plasma cells was detected in 4 Warthin
      tumors and none in the pleomorphic adenomas. Moreover, activation-induced
      cytidine deaminase, IgG4 germline transcripts, and productive IgG4 messenger RNA
      were found to be expressed in 2 of 3 Warthin tumors as well as IgG4-RDs by
      reverse transcription polymerase chain reaction, but not in pleomorphic adenomas.
      In conclusion, immunoglobulin class switching to IgG4 may be involved in the
      pathogenesis of Warthin tumor, and it is possible that certain inflammatory
      background with an immune reaction is involved in the pathogenesis of Warthin
      tumor. 

PMID- 24565205
TI  - Multiple gastrointestinal stromal tumors with novel germline c-kit gene mutation,
      K642T, at exon 13.
AB  - Multiple gastrointestinal stromal tumors (GISTs) caused by germline c-kit gene
      mutations are an extremely rare autosomal dominant disorder. A 57-year-old
      Japanese woman was referred to a hospital for appetite loss and severe weight
      loss. She had 2 large abdominal masses around the stomach, which were surgically
      resected. Histological examination revealed that these tumors were GISTs.
      Multiple microscopic GISTs and diffuse hyperplasia of the interstitial cells of
      Cajal were also seen in the background gastric and small intestinal walls.
      Characteristically, the GISTs showed severe hyalinization with calcification and
      partial heterotopic ossification, which may have caused the patient's severe
      dysphagia. Mutational analysis of the c-kit gene revealed a substitution at codon
      642 in exon 13 (K642T) in the tumor, normal ileal mucosa and peripheral blood
      leukocytes, indicating that the mutation is in the germline. This is the first
      case of multiple GISTs with novel germline c-kit gene mutation at exon 13.

PMID- 24565206
TI  - Composite lymphoid neoplasm of B-cell and T-cell origins: a pathologic study of
      14 cases.
AB  - We retrospectively analyzed 14 composite lymphoma/lymphoid neoplasms (CL) of B
      cell/T-cell origins. These consisted of a spectrum of T-cell neoplasms in
      combination with different B-cell lymphomas/leukemias, with peripheral T-cell
      lymphoma and diffuse large B-cell lymphoma encountered most frequently for each
      respective neoplastic lineage. Histopathologic evaluation demonstrated 6 patterns
      of neoplastic distribution, including zone, inverted zone, diffuse mixed,
      regional/nodular mixed, compartmental, and segmental distributions. Four of 9
      cases studied were positive for Epstein-Barr virus, all with a mixed pattern,
      suggesting that this pattern may predict an Epstein-Barr virus association. None
      of 14 cases was considered CL at the initial histologic evaluation. Only 6
      (46.2%) of 13 cases had coexisting B-cell/T-cell neoplasms highlighted by
      immunohistochemistry, and the other 7 (53.8%) cases had 1 or both of the
      neoplastic components hidden. Flow cytometry detected both neoplastic lineages in
      4 (44%) but failed to detect a clonal B-cell population in 4 (44%) and missed
      neoplastic T cells in 1 (11.1%) of 9 cases. Molecular testing detected clonal
      rearrangement of IGH/K gene in 11 (84.6%) of 13 cases, and clonal rearrangement
      of the TCRG/B gene in 13 (92.9%) of 14 cases, including 8 with identical
      amplicons detected in separate samples. CLs of B-cell/T-cell origin are
      heterogeneous in subtype combination and topographic pattern, often with one of
      the components histologically occult. A multidisciplinary approach is emphasized
      to establish a definitive diagnosis in these challenging cases. 

PMID- 24565207
TI  - Penile intraepithelial neoplasia with pagetoid features: report of an unusual
      variant mimicking Paget disease.
AB  - Precancerous lesions of the penis frequently share the morphologic features of
      the invasive counterpart. We have recently subclassified penile intraepithelial
      neoplasia into differentiated, warty, and basaloid subtypes, each one with
      distinctive microscopic morphology. Nevertheless, in our experience, some cases
      depart from this classification scheme and show unusual morphologic features,
      hindering the proper diagnosis on routine morphology alone. Herein we present a
      case of penile intraepithelial neoplasia with a pagetoid growth pattern, closely
      mimicking Paget disease. We describe the necessary steps to reach the final
      diagnose, including the use of immunohistochemistry for cytokeratin (CK) 7, CK20,
      CK34betaE12, CAM 5.2, AE1/AE3, CEA, S100, Melan-A, and p63. We also discuss other
      differential diagnoses that should be considered such as malignant melanoma and
      urothelial carcinoma in situ with pagetoid spread and less common lesions such as
      pagetoid dyskeratosis, clear cell papulosis, and mucinous metaplasia. 

PMID- 24565208
TI  - Recurrent papillary urothelial neoplasm of low malignant potential. Subtle
      architectural disorder detected by quantitative analysis in DAXX-immunostained
      tissue sections.
AB  - The aim of the study was to identify subtle changes in the so-called
      architectural predominant order in nonrecurrent and recurrent papillary
      urothelial neoplasm of low malignant potential (PUNLMP). Quantitative analysis
      was performed with a software package written in LabVIEW (National Instruments,
      Austin, TX) in DAXX-immunostained tissue sections. Twelve cases of PUNLMP with
      papillary fronds sectioned lengthwise through the core were investigated and
      subdivided as follows: 7 nonrecurrent and 5 recurrent PUNLMP cases. Six cases of
      normal urothelium (NU) were included. When an epithelial thickness threshold is
      set at 108 MUm (ie, 400 pixels), there is a complete separation between NU and
      PUNLMP; however, nonrecurrent and recurrent cases fall in the same range of
      thickness. In setting a nuclear elongation factor threshold at 2.1, there are
      differences between the 2 PUNLMP groups, recurrent PUNLMP and NU cases, showing a
      somewhat similar proportion of elongated nuclei. The nuclear orientation
      separates nonrecurrent from recurrent PUNLMP groups; however, NU cases do not
      appear as a separate group from the 2 PUNLMP groups. In combining epithelial
      thickness, nuclear elongation, and orientation in a multivariate analysis, the 2
      PUNLMP groups appear separate between them and from NU. NU is less thickened than
      the 2 PUNLMP groups and shows a combination of elongated and less elongated
      nuclei. Elongated nuclei are more numerous in nonrecurrent PUNLMP, whereas the
      nuclei in recurrent PUNLMP are less elongated and less polarized than in the
      other group. Such finding can be used routinely to identify those PUNLMP patients
      who will have recurrence. 

PMID- 24565209
TI  - How research funding agencies support science integration into policy and
      practice: an international overview.
AB  - BACKGROUND: Funding agencies constitute one essential pillar for policy makers,
      researchers and health service delivery institutions. Such agencies are
      increasingly providing support for science implementation. In this paper, we
      investigate health research funding agencies and how they support the integration
      of science into policy, and of science into practice, and vice versa. METHODS: We
      selected six countries: Australia, The Netherlands, France, Canada, England and
      the United States. For 13 funding agencies, we compared their intentions to
      support, their actions related to science integration into policy and practice,
      and the reported benefits of this integration. We did a qualitative content
      analysis of the reports and information provided on the funding agencies'
      websites. RESULTS: Most funding agencies emphasized the importance of science
      integration into policy and practice in their strategic orientation, and stated
      how this integration was structured. Their funding activities were embedded in
      the push, pull, or linkage/exchange knowledge transfer model. However, few
      program funding efforts were based on all three models. The agencies reported
      more often on the benefits of integration on practice, rather than on policy.
      External programs that were funded largely covered science integration into
      policy and practice at the end of grant stage, while overlooking the initial
      stages. Finally, external funding actions were more prominent than internally
      initiated bridging activities and training activities on such integration.
      CONCLUSIONS: This paper contributes to research on science implementation because
      it goes beyond the two community model of researchers versus end users, to
      include funding agencies. Users of knowledge may be end users in health
      organizations like hospitals; civil servants assigned to decision making
      positions within funding agencies; civil servants outside of the Ministry of
      Health, such as the Ministry of the Environment; politicians deciding on health
      related legislation; or even university researchers whose work builds on previous
      research. This heterogeneous sample of users may require different user-specific
      mechanisms for research initiation, development and dissemination. This paper
      builds the foundation for further discussion on science implementation from the
      perspective of funding agencies in the health field. In general, case studies can
      help in identifying best practices for evidence-informed decision making.

PMID- 24565210
TI  - Dermoscopic features of pagetoid dyskeratosis of the palm.

PMID- 24565211
TI  - Ulnar entrapment neuropathy in patients with type 2 diabetes mellitus: an
      electrodiagnostic study.
AB  - AIMS: This study aimed to assess the prevalence and electrophysiological features
      of ulnar entrapment neuropathy in patients with type 2 diabetes mellitus (DM).
      METHODS: Nerve conduction studies (NCS) were performed in a sample of consecutive
      diabetic patients aged 25-75 years, referred by the Diabetology Unit. NCS of the
      median, ulnar, radial, peroneal and sural nerves were performed on the non
      dominant side. Median entrapment neuropathy at the wrist (MNW) and ulnar
      neuropathy at the elbow (UNE) and wrist (UNW) were diagnosed according to
      standard electrodiagnostic criteria. RESULTS: Sixty-four patients were enrolled,
      28 male (44%), average age 61, average DM duration 14.5 years. Polyneuropathy was
      diagnosed in 45 subjects (70%). UNE was detected in 22 patients (34%) (4 did not
      have polyneuropathy), in the abductor digiti minimi in 16, the first interosseus
      in 14 and in both in 8. UNW was detected in 7 (11%) subjects and MNW in 40 (63%).
      NCS alterations consistent with ulnar neuropathy were detected in a high
      proportion of patients (45%), suggesting that the ulnar nerve is very susceptible
      to focal entrapment in DM. CONCLUSIONS: Upper limb sensory and motor NCS,
      including motor conduction velocity across the elbow, should be considered in the
      staging of DM patients.

PMID- 24565212
TI  - Post-absorptive glucose lowering in normal healthy individuals: an
      epidemiological observation.
AB  - Post-absorptive glucose lowering (PALG) is observed in individuals with glucose
      intolerance and in healthy individuals. We report a prevalence of about 23% among
      healthy Asian Indians. Individuals with PALG are characterized by leaner
      phenotype, low body fat percentage, increased insulin sensitivity and higher
      fasting glucose levels.

PMID- 24565213
TI  - Trends in recorded capillary blood glucose and hypoglycaemia in hospitalised
      patients with diabetes.
AB  - AIMS: To utilise whole-system analysis of capillary glucose measurement results
      to examine trends in timing of glucose monitoring, and to investigate whether
      these timings are appropriate based on observed patterns of hypoglycaemia.
      METHODS: Near-patient capillary blood glucose results from eight acute hospitals
      collected over 57 months were analysed. Analysis of frequency of measurement, and
      measurements in the hypoglycaemic (<4mmol/l) and severe hypoglycaemic (<2.5mol/l)
      range per time of day was made. RESULTS: 3345241 capillary glucose measurements
      were analysed. 1657594 capillary blood glucose values were associated with 106624
      admissions in those categorised as having diabetes. Large peaks in frequency of
      glucose measurements occurred before meals, with the highest frequency of
      capillary glucose measurement activity being seen pre-breakfast. Overnight, an
      increase in measurement activity was seen each hour. This pattern was mirrored by
      frequency of measured hypoglycaemia. 27968 admissions (26.2%) were associated
      with at least one hypoglycaemic measurement. A greater proportion of measurements
      were within the hypoglycaemic range overnight with 61.7% of all hypoglycaemia
      between 2100 and 0900h, with peak risk of measured capillary glucose being
      hypoglycaemic between 0300 and 0400h. CONCLUSIONS: Hypoglycaemic is common with
      the greatest risk of hypoglycaemia overnight and a peak percentage of all
      readings taken being in the hypoglycaemic range between 0300 and 0400h.
      Measurement activity overnight was driven by routine, with patterns of proportion
      of measurements in the hypoglycaemic range indicating that there may be a
      significant burden of undiscovered hypoglycaemia in the patients not routinely
      checked overnight.

PMID- 24565215
TI  - Definitions of dementia and predementia states in Alzheimer's disease and
      vascular cognitive impairment: consensus from the Canadian conference on
      diagnosis of dementia.
AB  - There have been several newly proposed sets of diagnostic criteria for
      Alzheimer's disease/mild cognitive impairment, advanced by the National Institute
      of Aging/Alzheimer's Association working groups in 2011 and by the International
      Working Group in 2007 and 2010. These sets each aim to provide broader disease
      stage coverage with incorporation of disease biomarkers into the diagnostic
      process. They have focused particular attention on the earlier identification of
      disease with focus on the preclinical and predementia stages. This paper reviews
      these diagnostic criteria and provides 2012 consensus recommendations from the
      Canadian Consensus Conference on the Diagnosis and Treatment of Dementia on their
      applications in both clinical and research settings. 

PMID- 24565214
TI  - Collecting and analysing cost data for complex public health trials: reflections
      on practice.
AB  - BACKGROUND: Current guidelines for the conduct of cost-effectiveness analysis
      (CEA) are mainly applicable to facility-based interventions in high-income
      settings. Differences in the unit of analysis and the high cost of data
      collection can make these guidelines challenging to follow within public health
      trials in low- and middle- income settings. OBJECTIVE: This paper reflects on the
      challenges experienced within our own work and proposes solutions that may be
      useful to others attempting to collect, analyse, and compare cost data between
      public health research sites in low- and middle- income countries. DESIGN: We
      describe the generally accepted methods (norms) for collecting and analysing cost
      data in a single-site trial from the provider perspective. We then describe our
      own experience applying these methods within eight comparable cluster randomised,
      controlled, trials. We describe the strategies used to maximise adherence to the
      norm, highlight ways in which we deviated from the norm, and reflect on the
      learning and limitations that resulted. RESULTS: When the expenses incurred by a
      number of small research sites are used to estimate the cost-effectiveness of
      delivering an intervention on a national scale, then deciding which expenses
      constitute 'start-up' costs will be a nontrivial decision that may differ among
      sites. Similarly, the decision to include or exclude research or monitoring and
      evaluation costs can have a significant impact on the findings. We separated out
      research costs and argued that monitoring and evaluation costs should be reported
      as part of the total trial cost. The human resource constraints that we
      experienced are also likely to be common to other trials. As we did not have an
      economist in each site, we collaborated with key personnel at each site who were
      trained to use a standardised cost collection tool. This approach both
      accommodated our resource constraints and served as a knowledge sharing and
      capacity building process within the research teams. CONCLUSIONS: Given the
      practical reality of conducting randomised, controlled trials of public health
      interventions in low- and middle- income countries, it is not always possible to
      adhere to prescribed guidelines for the analysis of cost effectiveness.
      Compromises are frequently required as researchers seek a pragmatic balance
      between rigor and feasibility. There is no single solution to this tension but
      researchers are encouraged to be mindful of the limitations that accompany
      compromise, whilst being reassured that meaningful analyses can still be
      conducted with the resulting data.

PMID- 24565217
TI  - An effective evolutionary algorithm for protein folding on 3D FCC HP model by
      lattice rotation and generalized move sets.
AB  - BACKGROUND: Proteins are essential biological molecules which play vital roles in
      nearly all biological processes. It is the tertiary structure of a protein that
      determines its functions. Therefore the prediction of a protein's tertiary
      structure based on its primary amino acid sequence has long been the most
      important and challenging subject in biochemistry, molecular biology and
      biophysics. In the past, the HP lattice model was one of the ab initio methods
      that many researchers used to forecast the protein structure. Although these
      kinds of simplified methods could not achieve high resolution, they provided a
      macrocosm-optimized protein structure. The model has been employed to investigate
      general principles of protein folding, and plays an important role in the
      prediction of protein structures. METHODS: In this paper, we present an improved
      evolutionary algorithm for the protein folding problem. We study the problem on
      the 3D FCC lattice HP model which has been widely used in previous research. Our
      focus is to develop evolutionary algorithms (EA) which are robust, easy to
      implement and can handle various energy functions. We propose to combine three
      different local search methods, including lattice rotation for crossover, K-site
      move for mutation, and generalized pull move; these form our key components to
      improve previous EA-based approaches. RESULTS: We have carried out experiments
      over several data sets which were used in previous research. The results of the
      experiments show that our approach is able to find optimal conformations which
      were not found by previous EA-based approaches. CONCLUSIONS: We have investigated
      the geometric properties of the 3D FCC lattice and developed several local search
      techniques to improve traditional EA-based approaches to the protein folding
      problem. It is known that EA-based approaches are robust and can handle arbitrary
      energy functions. Our results further show that by extensive development of local
      searches, EA can also be very effective for finding optimal conformations on the
      3D FCC HP model. Furthermore, the local searches developed in this paper can be
      integrated with other approaches such as the Monte Carlo and Tabu searches to
      improve their performance.

PMID- 24565218
TI  - A novel two-layer SVM model in miRNA Drosha processing site detection.
AB  - BACKGROUND: MicroRNAs (miRNAs) are a large class of non-coding RNAs with
      important functions wide spread in animals, plants and viruses. Studies showed
      that an RNase III family member called Drosha recognizes most miRNAs, initiates
      their processing and determines the mature miRNAs. The Drosha processing sites
      identification will shed some light on both miRNA identification and
      understanding the mechanism of Drosha processing. METHODS: We developed a
      computational method for Drosha processing site predicting, named as DroshaPSP,
      which employs a two-layer mathematical model to integrate structure feature in
      the first layer and sequence features in the second layer. The performance of
      DroshaPSP was estimated by 5-fold cross-validation and measured by ACC
      (accuracy), Sn (sensitivity), Sp (specificity), P (precision) and MCC (Matthews
      correlation coefficient). RESULTS: The results of testing DroshaPSP on the miRNA
      data of Drosophila melanogaster indicated that the Sn, Sp, and MCC thereof reach
      to 0.86, 0.99 and 0.86 respectively. CONCLUSIONS: We found the Shannon entropy, a
      chemical kinetics feature, is a significant feature in telling the true sites
      among the nearby sites and improving the performance.

PMID- 24565216
TI  - Media, messages, and medication: strategies to reconcile what patients hear, what
      they want, and what they need from medications.
AB  - BACKGROUND: Over the past 30 years, patients' options for accessing information
      about prescription drugs have expanded dramatically. In this narrative review, we
      address four questions: (1) What information sources are patients exposed to, and
      are they paying attention? (2) Is the information they hear credible and
      accurate? (3) When patients ask for a prescription, what do they really want and
      need? Finally, (4) How can physicians reconcile what patients hear, want, and
      need? ANALYSIS: A critical synthesis of the literature is reported. Observations
      indicate that the public is generally aware of and attends to a growing body of
      health information resources, including traditional news media, advertising, and
      social networking. However, lay audiences often have no reliable way to assess
      the accuracy of health information found in the media, on the Internet, or in
      direct-to-consumer advertising. This inability to assess the information can lead
      to decision paralysis, with patients questioning what is known, what is knowable,
      and what their physicians know. Many patients have specific expectations for the
      care they wish to receive and have little difficulty making those expectations
      known. However, there are hazards in assuming that patients' expressed desires
      are direct reflections of their underlying wants or needs. In trying to reconcile
      patients' wants and needs for information about prescription medicines, a
      combination of policy and clinical initiatives may offer greater promise than
      either approach alone. CONCLUSIONS: Patients are bombarded by information about
      medicines. The problem is not a lack of information; rather, it is knowing what
      information to trust. Making sure patients get the medications they need and are
      prepared to take them safely requires a combination of policy and clinical
      interventions.

PMID- 24565219
TI  - Integrating fMRI and SNP data for biomarker identification for schizophrenia with
      a sparse representation based variable selection method.
AB  - BACKGROUND: In recent years, both single-nucleotide polymorphism (SNP) array and
      functional magnetic resonance imaging (fMRI) have been widely used for the study
      of schizophrenia (SCZ). In addition, a few studies have been reported integrating
      both SNPs data and fMRI data for comprehensive analysis. METHODS: In this study,
      a novel sparse representation based variable selection (SRVS) method has been
      proposed and tested on a simulation data set to demonstrate its multi-resolution
      properties. Then the SRVS method was applied to an integrative analysis of two
      different SCZ data sets, a Single-nucleotide polymorphism (SNP) data set and a
      functional resonance imaging (fMRI) data set, including 92 cases and 116
      controls. Biomarkers for the disease were identified and validated with a
      multivariate classification approach followed by a leave one out (LOO) cross
      validation. Then we compared the results with that of a previously reported
      sparse representation based feature selection method. RESULTS: Results showed
      that biomarkers from our proposed SRVS method gave significantly higher
      classification accuracy in discriminating SCZ patients from healthy controls than
      that of the previous reported sparse representation method. Furthermore, using
      biomarkers from both data sets led to better classification accuracy than using
      single type of biomarkers, which suggests the advantage of integrative analysis
      of different types of data. CONCLUSIONS: The proposed SRVS algorithm is effective
      in identifying significant biomarkers for complicated disease as SCZ. Integrating
      different types of data (e.g. SNP and fMRI data) may identify complementary
      biomarkers benefitting the diagnosis accuracy of the disease.

PMID- 24565220
TI  - Missing value imputation for microarray data: a comprehensive comparison study
      and a web tool.
AB  - BACKGROUND: Microarray data are usually peppered with missing values due to
      various reasons. However, most of the downstream analyses for microarray data
      require complete datasets. Therefore, accurate algorithms for missing value
      estimation are needed for improving the performance of microarray data analyses.
      Although many algorithms have been developed, there are many debates on the
      selection of the optimal algorithm. The studies about the performance comparison
      of different algorithms are still incomprehensive, especially in the number of
      benchmark datasets used, the number of algorithms compared, the rounds of
      simulation conducted, and the performance measures used. RESULTS: In this paper,
      we performed a comprehensive comparison by using (I) thirteen datasets, (II) nine
      algorithms, (III) 110 independent runs of simulation, and (IV) three types of
      measures to evaluate the performance of each imputation algorithm fairly. First,
      the effects of different types of microarray datasets on the performance of each
      imputation algorithm were evaluated. Second, we discussed whether the datasets
      from different species have different impact on the performance of different
      algorithms. To assess the performance of each algorithm fairly, all evaluations
      were performed using three types of measures. Our results indicate that the
      performance of an imputation algorithm mainly depends on the type of a dataset
      but not on the species where the samples come from. In addition to the
      statistical measure, two other measures with biological meanings are useful to
      reflect the impact of missing value imputation on the downstream data analyses.
      Our study suggests that local-least-squares-based methods are good choices to
      handle missing values for most of the microarray datasets. CONCLUSIONS: In this
      work, we carried out a comprehensive comparison of the algorithms for microarray
      missing value imputation. Based on such a comprehensive comparison, researchers
      could choose the optimal algorithm for their datasets easily. Moreover, new
      imputation algorithms could be compared with the existing algorithms using this
      comparison strategy as a standard protocol. In addition, to assist researchers in
      dealing with missing values easily, we built a web-based and easy-to-use
      imputation tool, MissVIA (http://cosbi.ee.ncku.edu.tw/MissVIA), which supports
      many imputation algorithms. Once users upload a real microarray dataset and
      choose the imputation algorithms, MissVIA will determine the optimal algorithm
      for the users' data through a series of simulations, and then the imputed results
      can be downloaded for the downstream data analyses.

PMID- 24565221
TI  - A randomized controlled trial of the efficacy and safety of twice-daily
      saxagliptin plus metformin combination therapy in patients with type 2 diabetes
      and inadequate glycemic control on metformin monotherapy.
AB  - BACKGROUND: To compare the safety and efficacy of saxagliptin 2.5 mg twice daily
      (BID) versus placebo add-on therapy to metformin immediate release (IR) in
      patients with type 2 diabetes and inadequate glycemic control with metformin
      alone. METHODS: This multicenter, 12-week, double-blind, parallel-group trial
      enrolled adult outpatients with type 2 diabetes (glycated hemoglobin [HbA1c] 7.0%
      10.0%) on stable metformin IR monotherapy (>=1500 mg, BID for >=8 weeks).
      Patients were randomized to double-blind saxagliptin 2.5 mg BID or placebo added
      on to metformin IR following a 2-week, single-blind, placebo add-on therapy lead
      in period. The primary end point was the change from baseline to week 12 in
      HbA1c. Key secondary end points included change from baseline to week 12 in
      fasting plasma glucose (FPG) and the proportion of patients achieving HbA1c <7.0%
      or HbA1c <= 6.5% at week 12. Efficacy was analyzed in all patients who received
      randomized study drug with >=1 postbaseline assessment. Safety was assessed in
      all treated patients. RESULTS: In total, 74 patients were randomized to double
      blind saxagliptin add-on therapy and 86 to placebo add-on therapy. At week 12,
      least-squares mean changes (95% CI) from baseline HbA1c (adjusted for baseline
      HbA1c) were significantly greater (P = 0.006) in the saxagliptin + metformin
      group -0.56% (-0.74% to -0.38%) versus the placebo + metformin group -0.22% (
      0.39% to -0.06%). Adjusted mean changes from baseline in FPG were numerically
      greater with saxagliptin versus placebo; the difference (95% CI) -9.5 mg/dL (
      21.7 to 2.7) was not statistically significant (P = 0.12). A numerically greater
      proportion of patients in the saxagliptin group than the placebo group achieved
      HbA1c < 7.0% (37.5% vs 24.2%) or HbA1c <=6.5% (24.6% vs 10.7%). There were no
      unexpected safety findings. Hypoglycemia occurred in 4 patients (5.4%) in the
      saxagliptin group and 1 patient (1.2%) in the placebo group; confirmed
      hypoglycemia (symptoms plus fingerstick glucose <=50 mg/dL) occurred in 1 patient
      in the placebo group. CONCLUSIONS: Addition of saxagliptin 2.5 mg BID to
      metformin therapy in patients with type 2 diabetes and inadequate glycemic
      control on metformin monotherapy reduced HbA1c compared with placebo added to
      metformin, with an adverse events profile similar to placebo and no unexpected
      safety findings. TRIAL REGISTRATION: ClinicalTrials.gov NCT00885378.

PMID- 24565222
TI  - Identifying novel glioma associated pathways based on systems biology level meta
      analysis.
AB  - BACKGROUND: With recent advances in microarray technology, including genomics,
      proteomics, and metabolomics, it brings a great challenge for integrating this "
      omics" data to analysis complex disease. Glioma is an extremely aggressive and
      lethal form of brain tumor, and thus the study of the molecule mechanism
      underlying glioma remains very important. To date, most studies focus on
      detecting the differentially expressed genes in glioma. However, the meta
      analysis for pathway analysis based on multiple microarray datasets has not been
      systematically pursued. RESULTS: In this study, we therefore developed a systems
      biology based approach by integrating three types of omics data to identify
      common pathways in glioma. Firstly, the meta-analysis has been performed to study
      the overlapping of signatures at different levels based on the microarray gene
      expression data of glioma. Among these gene expression datasets, 12 pathways were
      found in GeneGO database that shared by four stages. Then, microRNA expression
      profiles and ChIP-seq data were integrated for the further pathway enrichment
      analysis. As a result, we suggest 5 of these pathways could be served as putative
      pathways in glioma. Among them, the pathway of TGF-beta-dependent induction of
      EMT via SMAD is of particular importance. CONCLUSIONS: Our results demonstrate
      that the meta-analysis based on systems biology level provide a more useful
      approach to study the molecule mechanism of complex disease. The integration of
      different types of omics data, including gene expression microarrays, microRNA
      and ChIP-seq data, suggest some common pathways correlated with glioma. These
      findings will offer useful potential candidates for targeted therapeutic
      intervention of glioma.

PMID- 24565223
TI  - The occurrence and dominant controls on arsenic in the Newark and Gettysburg
      Basins.
AB  - Elevated arsenic (As) concentrations in groundwater and rocks have been found in
      crystalline and sedimentary aquifers from New England to Pennsylvania, USA. The
      arsenic geochemistry and water-rock interactions of the Northern Appalachian
      Mountains and the Newark Basin have been researched at length, however, little is
      known about arsenic in the Gettysburg Basin. Both the Newark and Gettysburg
      Basins were formed during the breakup of Pangea, sediment deposition occurred
      during the Triassic and lithologies are of similar depositional environment. We
      compile and review the work done in the Newark Basin and collect new samples in
      the Gettysburg Basin for comparison. The Gettysburg Basin has 18%-39% of rock
      samples with arsenic concentrations greater than the crustal average of 2 mg/kg,
      while the Newark Basin has 73% to 95% of rock samples above the crustal average.
      The strongest controls on arsenic in rocks of the Gettysburg Basin are the
      relationship between arsenic and iron and silicon concentrations while the
      strongest controls in the Newark Basin are the relationship between arsenic and
      iron and organic carbon concentrations. The groundwater arsenic concentrations
      follow similarly with 8-39% of water samples from the Gettysburg Basin above 10
      MUg/L and 24-54% of water samples from the Newark Basin above 10 MUg/L. The
      strongest controls on arsenic in water of the Gettysburg Basin are pH, alkalinity
      and silicon, while the strongest controls in the Newark Basin are pH and
      alkalinity.

PMID- 24565224
TI  - Concerning the manuscript "burnt sugarcane harvesting: particulate matter
      exposure and the effects on lung function, oxidative stress, and urinary 1
      hydroxypyrene".

PMID- 24565226
TI  - The value of personalized psychosocial interventions to address behavioral and
      psychological symptoms in people with dementia living in care home settings: a
      systematic review.
AB  - BACKGROUND: Several important systematic reviews and meta-analyses focusing on
      psychosocial interventions have been undertaken in the last decade. However, they
      have not focused specifically on the treatment of individual behavioral and
      psychological symptoms of dementia (BPSD) with personalized interventions. This
      updated systematic review will focus on studies reporting the effect of
      personalized psychosocial interventions on key BPSD in care homes. METHODS:
      Systematic review of the evidence for psychosocial interventions for BPSD,
      focusing on papers published between 2000 and 2012. All care home and nursing
      home studies including individual and cluster randomized controlled trials (RCTs)
      and pre-/post-test studies with control conditions were included. RESULTS: 641
      studies were identified, of which 40 fulfilled inclusion and exclusion criteria.
      There was good evidence to support the value of personalized pleasant activities
      with and without social interaction for the treatment of agitation, and
      reminiscence therapy to improve mood. The evidence for other therapies was more
      limited. CONCLUSIONS: There is a growing body of evidence indicating specific
      effects of different personalized psychosocial interventions on individual BPSD
      and mood outcomes.

PMID- 24565227
TI  - 'Single molecule': theory and experiments, an introduction.
AB  - At scales below micrometers, Brownian motion dictates most of the behaviors. The
      simple observation of a colloid is striking: a permanent and random motion is
      seen, whereas inertial forces play a negligible role. This Physics, where
      velocity is proportional to force, has opened new horizons in biology. The random
      feature is challenged in living systems where some proteins--molecular motors-
      have a directed motion whereas their passive behaviors of colloid should lead to
      a Brownian motion. Individual proteins, polymers of living matter such as DNA,
      RNA, actin or microtubules, molecular motors, all these objects can be viewed as
      chains of colloids. They are submitted to shocks from molecules of the solvent.
      Shapes taken by these biopolymers or dynamics imposed by motors can be measured
      and modeled from single molecules to their collective effects. Thanks to the
      development of experimental methods such as optical tweezers, Atomic Force
      Microscope (AFM), micropipettes, and quantitative fluorescence (such as Forster
      Resonance Energy Transfer, FRET), it is possible to manipulate these individual
      biomolecules in an unprecedented manner: experiments allow to probe the validity
      of models; and a new Physics has thereby emerged with original biological
      insights. Theories based on statistical mechanics are needed to explain behaviors
      of these systems. When force-extension curves of these molecules are extracted,
      the curves need to be fitted with models that predict the deformation of free
      objects or submitted to a force. When velocity of motors is altered, a
      quantitative analysis is required to explain the motions of individual molecules
      under external forces. This lecture will give some elements of introduction to
      the lectures of the session 'Nanophysics for Molecular Biology'.

PMID- 24565225
TI  - Design considerations for an integrated microphysiological muscle tissue for drug
      and tissue toxicity testing.
AB  - Microphysiological systems provide a tool to simulate normal and pathological
      function of organs for prolonged periods. These systems must incorporate the key
      functions of the individual organs and enable interactions among the
      corresponding microphysiological units. The relative size of different
      microphysiological organs and their flow rates are scaled in proportion to in
      vivo values. We have developed a microphysiological three-dimensional engineered
      human skeletal muscle system connected to a circulatory system that consists of a
      tissue-engineered blood vessel as part of a high-pressure arterial system. The
      engineered human skeletal muscle tissue reproduces key mechanical behaviors of
      skeletal muscle in vivo. Pulsatile flow is produced using a novel computer
      controlled magnetically activated ferrogel. The system is versatile and the
      muscle unit can be integrated with other organ systems. Periodic monitoring of
      biomechanical function provides a non-invasive assessment of the health of the
      tissue and a way to measure the response to drugs and toxins. 

PMID- 24565228
TI  - Social and organizational factors affecting implementation of evidence-informed
      practice in a public health department in Ontario: a network modelling approach.
AB  - OBJECTIVE: The objective of this study is to develop a statistical model to
      assess factors associated with information seeking in a Canadian public health
      department. METHODS: Managers and professional consultants of a public health
      department serving a large urban population named whom they turned to for help,
      whom they considered experts in evidence-informed practice, and whom they
      considered friends. Multilevel regression analysis and exponential random graph
      modeling were used to predict the formation of information seeking and expertise
      recognition connections by personal characteristics of the seeker and source, and
      the structural attributes of the social networks. RESULTS: The respondents were
      more likely to recognize the members of the supervisory/administrative division
      as experts. The extent to which an individual implemented evidence-based practice
      (EBP) principles in daily practice was a significant predictor of both being an
      information source and being recognized as expert by peers. Friendship was a
      significant predictor of both information seeking and expertise-recognition
      connections. CONCLUSION: The analysis showed a communication network segregated
      by organizational divisions. Managers were identified frequently as information
      sources, even though this is not a part of their formal role. Self-perceived
      implementation of EBP in practice was a significant predictor of being an
      information source or an expert, implying a positive atmosphere towards
      implementation of evidence-informed decision making in this public health
      organization. Results also implied that the perception of accessibility and trust
      were significant predictors of expertise recognition.

PMID- 24565229
TI  - Identifying disease associated genes by network propagation.
AB  - BACKGROUND: Genome-wide association studies have identified many individual genes
      associated with complex traits. However, pathway and network information have not
      been fully exploited in searches for genetic determinants, and including this
      information may increase our understanding of the underlying biology of common
      diseases. RESULTS: In this study, we propose a framework to address this problem
      in a principled way, with the underlying hypothesis that complex disease operates
      through multiple connected genes. Associations inferred from GWAS are translated
      into prior scores for vertices in a protein-protein interaction network, and
      these scores are propagated through the network. Permutation is used to select
      genes that are guilty-by-association and thus consistently obtain high scores
      after network propagation. We apply the approach to data of Crohn's disease and
      call candidate genes that have been reported by other independent GWAS, but not
      in the analysed data set. A prediction model based on these candidate genes show
      good predictive power as measured by Area Under the Receiver Operating Curve
      (AUC) in 10 fold cross-validations. CONCLUSIONS: Our network propagation method
      applied to a genome-wide association study increases association findings over
      other approaches.

PMID- 24565230
TI  - An improved sparse representation model with structural information for
      Multicolour Fluorescence In-Situ Hybridization (M-FISH) image classification.
AB  - BACKGROUND: Multicolour Fluorescence In-Situ Hybridization (M-FISH) images are
      employed for detecting chromosomal abnormalities such as chromosomal
      translocations, deletions, duplication and inversions. This technique uses mixed
      colours of fluorochromes to paint the whole chromosomes for rapid detection of
      chromosome rearrangements. The M-FISH data sets used in our research are obtained
      from microscopic scanning of a metaphase cell labelled with five different
      fluorochromes and a DAPI staining. The reliability of the technique lies in
      accurate classification of chromosomes (24 classes for male and 23 classes for
      female) from M-FISH images. However, due to imaging noise, mis-alignment between
      multiple channels and many other imaging problems, there is always a
      classification error, leading to wrong detection of chromosomal abnormalities.
      Therefore, how to accurately classify different types of chromosomes from M-FISH
      images becomes a challenging problem. METHODS: This paper presents a novel sparse
      representation model considering structural information for the classification of
      M-FISH images. In our previous work a sparse representation based classification
      model was proposed. This model employed only individual pixel information for the
      classification. With the structural information of neighbouring pixels as well as
      the information of themselves simultaneously, the novel approach extended the
      previous one to the regional case. Based on Orthogonal Matching Pursuit (OMP), we
      developed simultaneous OMP algorithm (SOMP) to derive an efficient solution of
      the improved sparse representation model by incorporating the structural
      information. RESULTS: The p-value of two models shows that the newly proposed
      model incorporating the structural information is significantly superior to our
      previous one. In addition, we evaluated the effect of several parameters, such as
      sparsity level, neighbourhood size, and training sample size, on the of the
      classification accuracy. CONCLUSIONS: The comparison with our previously used
      sparse model demonstrates that the improved sparse representation model is more
      effective than the previous one on the classification of the chromosome
      abnormalities.

PMID- 24565231
TI  - Conversion to mTOR-inhibitor-based immunosuppression: which patients and when?
AB  - Mammalian target of rapamycin (mTOR) inhibitors are currently considered an
      alternative immunosuppressive treatment that can prevent the nephrotoxicity,
      viral infections and malignancies that are associated with calcineurin inhibitor
      based immunosuppressive regimens. However, the side effects of mTOR-inhibitor
      based regimens lead to frequent treatment discontinuations, and not all patients
      seem to have the same benefits from conversion to mTOR inhibitors. This review
      focuses on long-term results of trials that have assessed early and late
      conversion to sirolimus or everolimus. The renal benefit of late conversion (>=1
      year post transplantation) is limited, except in patients with good renal
      function and without proteinuria. Early conversion to mTOR inhibitors in the
      first 6 months, in combination with mycophenolate mofetil, could be an
      appropriate strategy for maintenance therapy in renal transplant recipients with
      a low immunological risk after careful screening at the time of conversion. Good
      renal function (glomerular filtration rate >40 ml/ minute), weak proteinuria (<1
      g/day), an absence of previous acute rejection and subclinical rejection, and
      appearance of donor-specific anti-human leukocyte antigen antibodies appear to be
      the most important criteria in identifying patients for whom conversion to an
      mTOR inhibitor may improve renal function at 5 years. 

PMID- 24565232
TI  - Enhancing the separation performance of the first-generation silica monolith
      using active flow technology: parallel segmented flow mode of operation.
AB  - Active flow technology (AFT) columns are designed to minimise inefficient flow
      processes associated with the column wall and radial heterogeneity of the
      stationary phase bed. This study is the first to investigate AFT on an analytical
      scale 4.6mm internal diameter first-generation silica monolith. The performance
      was compared to a conventional first-generation silica monolith and it was
      observed that the AFT monolith had an increase in efficiency values that ranged
      from 15 to 111%; the trend demonstrating efficiency gains increasing as the
      volumetric flow to the detector was decreased, but with no loss in sensitivity. 

PMID- 24565233
TI  - Cucurbit[n]urils as a new class of stationary phases for gas chromatographic
      separations.
AB  - Cucurbit[n]urils (CBs) possess unique structures and physicochemical properties
      as well as excellent thermal stability. These characteristics concur to make them
      good candidates for stationary phases in capillary gas chromatographic (GC)
      separations. Herein, CB7 and CB8 in neat (CB7, CB8) and binary (CB7-CB8) forms
      were investigated for this purpose. After they were statically coated onto fused
      silica capillary columns, the CB columns were evaluated in terms of
      chromatographic parameters, separation performance, thermal stability and column
      repeatability. The columns had efficiencies ranging from 1060 to 2200 plates per
      meter determined by n-dodecane at 100 degrees C and exhibited nonpolar to weakly
      polar nature. These CBs columns showed good separation performance for a wide
      range of analytes such as n-alkanes, aromatic hydrocarbons, esters, aldehydes,
      ketones, alcohols and the Grob mixture, and exhibited nice peak shapes for
      analytes that are liable to peak-tailing in GC analysis. The results also proved
      the good column repeatability and thermal stability of the CB columns. No
      noticeable decreases in both retention times and resolution or appreciable
      baseline drift were observed after the columns were conditioned up to 250 degrees
      C (CB8 and CB7-CB8 columns) or 280 degrees C (CB7 column). This work demonstrates
      the promising future of CBs as a new class of GC stationary phase. To the best of
      our knowledge, this is the first report on using CB stationary phases in
      capillary GC separations. 

PMID- 24565234
TI  - Enantioseparation of beta(2)-amino acids on cinchona alkaloid-based zwitterionic
      chiral stationary phases. Structural and temperature effects.
AB  - The enantiomers of sixteen unusual beta(2)-amino acids were directly separated on
      chiral stationary phases containing quinine- or quinidine-based zwitterionic
      selectors. The effects of the mobile phase composition, the structure of the
      analyte and temperature on the separations were investigated. Experiments were
      performed at constant mobile phase compositions in the temperature range -5 to 55
      degrees C in order to study the effects of temperature, and thermodynamic
      parameters were estimated from plots of lnk or lnalpha vs. 1/T. Some mechanistic
      aspects of the chiral recognition process are discussed with respect to the
      structures of the analytes. It was found that the enantiomeric separations were
      in most cases enthalpically driven, but entropically driven separation was also
      observed. The sequence of elution of the enantiomers was determined in some
      cases. 

PMID- 24565235
TI  - Determination of phenolic compounds in honey using dispersive liquid-liquid
      microextraction.
AB  - Honey is a valuable functional food rich in phenolic compounds with a broad
      spectrum of biological activities. Analysis of the phenolic compounds in honey is
      a very promising tool for the quality control, the authentication and
      characterization of botanical origin, and the nutraceutical research. This work
      describes a novel approach for the rapid analysis of five phenolic acids and 10
      flavonoids in honey. Phenolic compounds were rapidly extracted and concentrated
      from diluted honey by dispersive liquid-liquid microextraction (DLLME) and then
      analyzed using high performance liquid chromatography with UV absorbance
      detection (HPLC-UV). Some important parameters, such as the nature and volume of
      extraction and dispersive solvents, pH and salt effect were carefully
      investigated and optimized to achieve the best extraction efficiency. Under the
      optimal conditions, an exhaustive extraction for twelve of the investigated
      analytes (recoveries >70%), with a precision (RSD<10%) highly acceptable for
      complex matrices, and detection and quantification limits at ppb levels (1.4-12
      and 4.7-40ngg(-1), respectively) were attained. The proposed method, compared
      with the most widely used method in the analysis of phenolic compounds in honey,
      provided similar or higher extraction efficiency, except in the case of the most
      hydrophilic phenolic acids. The capability of DLLME to the extraction of other
      honey phytochemicals, such as abscisic acid, was also demonstrated. The main
      advantages of developed method are the simplicity of operation, the rapidity to
      achieve a very high sample throughput and low cost. 

PMID- 24565236
TI  - Comparison of lornoxicam and fentanyl when added to lidocaine in intravenous
      regional anesthesia.
AB  - BACKGROUND AND OBJECTIVES: In this study, our goal was to compare intraoperative
      and postoperative analgesic effects of lornoxicam and fentanyl when added to
      lidocaine Intravenous Regional Anesthesia (IVRA) in a group of outpatients who
      underwent hand surgery. METHODS: This is a double blind randomized study. A total
      of 45 patients were included, randomized into three groups. Patients in Group I
      (L) received 3mg.kg(-1) of 2% lidocaine 40 mL; patients in Group II (LL) received
      3mg.kg(-1) lidocaine 38 mL + 2 mL lornoxicam; patients in Group III (LF) received
      3mg.kg(-1) lidocaine 38 mL + 2 mL fentanyl. Our primary outcome was first
      analgesic requirement time at postoperative period. RESULTS: Lornoxicam added to
      lidocaine IVRA increased the sensory block recovery time without increasing side
      effects and increased first analgesic requirement time at the postoperative
      period when compared to lidocaine IVRA (p < 0.001, p < 0.001 respectively) and
      fentanyl added to lidocaine IVRA (p < 0.001, p < 0.001 respectively). In
      addition, we also found that fentanyl decreased tourniquet pain (p < 0.01) when
      compared to lidocaine but showed similar analgesic effect with lornoxicam (p >
      0.05) although VAS scores related to tourniquet pain were lower in fentanyl
      group. Lornoxicam added to lidocaine IVRA was not superior to lidocaine IVRA in
      decreasing tourniquet pain. CONCLUSIONS: Addition of fentanyl to lidocaine IVRA
      seems to be superior to lidocaine IVRA and lornoxicam added to lidocaine IVRA
      groups in decreasing tourniquet pain at the expense of increasing side effects.
      However, lornoxicam did not increase side effects while providing intraoperative
      and postoperative analgesia. Therefore, lornoxicam could be more appropriate for
      clinical use.

PMID- 24565237
TI  - Association of pain catastrophizing with the incidence and severity of acute and
      persistent perineal pain after natural childbirth: longitudinal cohort study.
AB  - BACKGROUND AND OBJECTIVES: Vaginal birth delivery may result in acute and
      persistent perineal pain postpartum. This study evaluated the association between
      catastrophizing, a phenomenon of poor psychological adjustment to pain leading
      the individual to magnify the painful experience making it more intense, and the
      incidence and severity of perineal pain and its relationship to perineal trauma.
      METHOD: Cohort study conducted with pregnant women in labor. We used the pain
      catastrophizing scale during hospitalization and assessed the degree of perineal
      lesion and pain severity in the first 24 hours and after 8 weeks of delivery
      using a numerical pain scale. RESULTS: We evaluated 55 women, with acute pain
      reported by 69.1%, moderate/severe pain by 36.3%, and persistent pain by 14.5%.
      Catastrophizing mean score was 2.15 +/- 1.24. Catastrophizing patients showed a
      2.90 relative risk (RR) for perineal pain (95% CI: 1.08-7.75) and RR: 1.31 for
      developing persistent perineal pain (95% CI: 1.05-1.64). They also showed a RR:
      2.2 for developing acute and severe perineal pain (95% CI: 1.11-4.33).
      CONCLUSIONS: The incidence of acute and persistent perineal pain after vaginal
      delivery is high. Catastrophizing pregnant women are at increased risk for
      developing acute and persistent perineal pain, as well as severe pain. Perineal
      trauma increased the risk of persistent perineal pain.

PMID- 24565238
TI  - Comparative study related to cardiovascular safety between bupivacaine (S75-R25)
      and ropivacaine in brachial plexus block.
AB  - BACKGROUND AND OBJECTIVES: Bupivacaine is a first choice for regional anesthesia
      considering its effectiveness, long duration and less motor blockade. Bupivacaine
      (S75-R25) is a mixture of optical isomers containing 75% levobupivacaine (S-) and
      25% dextrobupivacaine (R+) created by a Brazilian pharmaceutical company. This
      investigation compared cardiac safety and efficacy of bupivacaine S75-R25 with
      vasoconstrictor and ropivacaine for brachial plexus blockade. METHODS: Patients
      were randomized to receive brachial plexus anesthesia with either bupivacaine S75
      R25 with epinephrine 1:200,000 (bupi) or ropivacaine (ropi), both at 0.50%, in 30
      mL solution. We registered a continuous Holter ECG throughout the procedure, as
      well as the Lovett scale of force in addition to monitoring (heart rate, pulse
      oximetry and non-invasive blood pressure). The incidence of adverse events was
      compared with the chi-square or Fisher test. RESULTS: We allocated forty-four
      patients into two groups. They did not show any difference related to age, weight
      or height, gender, as well as for surgical duration. Supraventricular arrhythmias
      were not different before or after the plexus blockade, independent of the local
      anesthetic chosen. Loss of sensitivity was faster for the bupivacaine group (23.1
      +/- 11.7 min) compared to the ropivacaine one (26.8 +/- 11.5 min), though not
      significant (p = 0.205, Student t). There was a reduction in the cardiac rate,
      observed during the twenty-four-hour Holter monitoring. CONCLUSIONS: This study
      showed similar efficacy between bupivacaine S75-R25 for brachial plexus blockade
      and ropivacaine, with similar incidences of supraventricular arrhythmias.

PMID- 24565239
TI  - Risk factors for perioperative complications in endoscopic surgery with
      irrigation.
AB  - BACKGROUND AND OBJECTIVES: Currently, endoscopic medicine is being increasingly
      used, albeit not without risks. Therefore, this study evaluated the factors
      associated with perioperative complications in endoscopic surgery with
      intraoperative irrigation. METHOD: A cohort study of six months duration.
      Patients aged >= 18 years undergoing endoscopic surgery with the use of
      irrigation fluids during the intraoperative period were included. Exclusion
      criteria were: use of diuretics, kidney failure, cognitive impairment,
      hyponatremia prior to surgery, pregnancy, and critically ill. The patients who
      presented with or without complications during the perioperative period were
      allocated into two groups. Complications evaluated were related to neurological,
      cardiovascular and renal changes, and perioperative bleeding. RESULTS: In total,
      181 patients were enrolled and 39 excluded; therefore, 142 patients met the study
      criteria. Patients with complications amounted to 21.8%, with higher prevalence
      in endoscopic prostate surgery, followed by hysteroscopy, bladder, knee, and
      shoulder arthroscopy (58.1%, 36.9%, 19.4%, 3.8%, 3.2% respectively). When
      comparing both groups, we found association with complications in univariate
      analysis: age, sex, smoking, heart disease, ASA, serum sodium at the end of
      surgery, total irrigation fluid administered, TURP, and hysteroscopy. However, in
      multiple regression analysis for complications, only age (OR = 1.048), serum
      sodium (OR = 0.962), and volume of irrigation fluid administered during surgery
      (OR = 1.001) were independent variables. CONCLUSION: The incidence of serious
      complications in endoscopic surgeries is high. Serum sodium at the end of the
      operation, amount of irrigation fluid, and age were strong independent factors
      associated with the problem. Thus, these factors must be taken into account in
      these surgeries.

PMID- 24565240
TI  - Ilioinguinal-iliohypogastric nerve block with intravenous dexketoprofen improves
      postoperative analgesia in abdominal hysterectomies.
AB  - BACKGROUND AND OBJECTIVE: In this study, our aim was to evaluate the effects of
      intravenous dexketoprofen trometamol with ilioinguinal and iliohypogastric nerve
      block on analgesic quality and morphine consumption after total abdominal
      hysterectomy operations. METHODS: We conducted this randomized controlled
      clinical study on 61 patients. The study was conducted in the operation room,
      post-anesthesia care unit, and inpatient clinic. We randomly grouped the 61
      patients into control group (group C), block group (group B) and dexketoprofen
      block group (group DB). Before the skin incision performed after anesthesia
      induction, we performed ilioinguinal iliohypogastric block (group C given saline
      and group P and DB given levobupivacaine). In contrast to group C and B, group DB
      was given dexketoprofen. We administered morphine analgesia to all patients by
      patient-controlled analgesia (PCA) during the postoperative 24 hours. We recorded
      Visual Analogue Scale (VAS), satisfaction scores, morphine consumption and side
      effects during postoperative 24 hours. RESULTS: We found the DB group's VAS
      scores to be lower than the control group and block group's (p < 0.05) values at
      postoperative 1(st), 2(nd), 6(th) and 12(th) hours. VAS scores of group C were
      higher than of group B at postoperative first 2 hours. Time to first PCA demand
      was longer, morphine consumption values were lower and satisfaction scores were
      higher in group DB than in the other two groups (p < 0.05). CONCLUSIONS:
      Ilioinguinal-iliohypogastric nerve block with IV dexketoprofen increases patient
      satisfaction by decreasing opioid consumption, increasing patient satisfaction,
      which suggests that dexketoprofen trometamol is an effective non-steroidal anti
      inflammatory analgesic in postoperative analgesia.

PMID- 24565241
TI  - Postoperative nausea and vomiting: Validation of the Portuguese version of the
      Postoperative Nausea and Vomiting Intensity Score.
AB  - BACKGROUND AND OBJECTIVES: The Postoperative Nausea and Vomiting (PONV) Intensity
      Scale was developed to define clinically important PONV. The aim of this study
      was to translate, retranslate and validate the PONV Intensity Scale for use in
      Portuguese Post Anesthetic Care Unit (PACU) settings. METHODS: The PONV Intensity
      Scale was translated and back-translated in accordance with available guidelines.
      The research team conducted an observational and cohort prospective study in a
      PACU. One-hundred fifty-seven adult patients admiited after surgery over three
      weeks were evaluated for PONV. Measurements included nausea visual analogic scale
      (VAS) at 6 and 24 hours, postoperatively. We assessed reliability and observer
      disagreement using interclass correlation (ICC) and Information-Based Measure of
      Disagreement (IBMD). We compared VAS scores between patients with clinically
      significant (>=50) and not significant (<50) PONV. RESULTS: Thirty-nine patients
      (25%) had PONV at 6 hours and 54 (34%) had PONV at 24 hours. Thirty-six and 54
      patients experienced nausea at 6 and 24 hours, respectively. Among patients with
      PONV, 6 patients (15%) and 9 patients (27%) had a clinically significant PONV
      intensity scale score at 6 and at 24 hours, respectively. The reliability was
      good both for PONV intensity scale score and for VAS and observer disagreement
      was slightly higher for VAS. The median nausea VAS scores were higher in patients
      with clinically significant PONV Intensity score. CONCLUSIONS: The PONV Intensity
      Scale appears to be an accurate and reliable assessment and monitoring instrument
      for PONV in the PACU settings.

PMID- 24565242
TI  - Preoperative evaluation: screening using a questionnaire.
AB  - BACKGROUND AND OBJECTIVE: Prior to elective surgery it is essential to know in
      advance the patient's clinical condition. The aim of this study was to compare
      the preoperative evaluation (POE) through questionnaire responses with
      preanesthetic evaluation by the anesthesiologist. METHOD: Prior to their
      preoperative evaluation, patients answered a questionnaire with information
      regarding age, weight, height, scheduled surgery, past medical and surgical
      history, allergies, medications and doses used, social history (illicit drugs,
      alcohol, smoking), functional capacity and exercise tolerance. Preoperative
      evaluation was performed by an anesthesiologist who had no access to the
      questionnaire data or knowledge about the research. The questionnaire data were
      compared with the preoperative evaluation by two independent investigators, in
      order to answer the questions: 1) Was the questionnaire evaluation effective -
      could the patient undergo surgery without the need for face-to-face consultation?
      2) Has been there any relevant information - ability to change the anesthetic
      approach - not assessed by the questionnaire, but assessed by the face-to-face
      consultation? 3) Has been there any information added by the health questionnaire
      that was missed by face-to-face consultation? For statistical analysis, the
      paired Student's t-test was used for parametric data and chi-square test for
      categorical data, with p < 0.05 considered significant. RESULTS: Of the 269
      eligible patients there was one refusal, and four agreed to participate but did
      not complete the questionnaire, in addition to 52 losses, totaling 212
      participants. Questionnaire data added to the consultation in 109 cases (51.4%).
      The screening questionnaire alone was effective for 144 patients (67.93%), with
      no need for consultation. The anesthesiologist evaluation referred patients for
      surgery on their first visit in 178 opportunities (84%). In the identification of
      cases of non-referral to surgery, the questionnaire showed a negative predictive
      value of 94.4%, positive predictive value of 38.2%, sensitivity of 76.5%, and
      specificity of 76.4%. Statistically significant (P < 0.05) clinical factors
      associated with non-referral to surgery were: age over 65 years, BMI > 30, low
      functional capacity, hypertension, diabetes mellitus, asthma, renal failure,
      hepatitis, and ischemic heart disease. CONCLUSION: The questionnaire was
      effective for screening patients who needed further evaluation and/or changes in
      treatment regimen prior to elective surgery. Moreover, the questionnaire added
      data not covered by clinical evaluation.

PMID- 24565243
TI  - Sedation-analgesia in elective colonoscopy: propofol-fentanyl versus propofol
      alfentanil.
AB  - BACKGROUND AND OBJECTIVES: Sedation-analgesia is recommended for comfortable
      colonoscopy procedures, which are invasive and can be painful. This study aimed
      to compare the combinations of propofol-alfentanil and propofol-fentanyl for
      sedation-analgesia in elective colonoscopy patients. METHODS: This prospective
      and randomized study was planned in ASA I-II groups and included 80 patients
      between the ages of 18 and 65 years. Sedation-analgesia induction was performed
      as 1 MUg.kg(-1) fentanyl, 1mg.kg(-1) propofol in the propofol-fentanyl group
      (Group PF) and 10 MUg.kg(-1) alfentanil, 1mg.kg(-1) propofol in the propofol
      alfentanil group (Group PA). Patients' scores were limited to 3-4 values on the
      Ramsey Sedation Scale (RSS) by 0.5mg.kg(-1) bolus additional doses of propofol in
      sedation-analgesia maintenance. We recorded demographical data, heart rate, mean
      arterial pressure (MAP), oxygen saturation of hemoglobin (SpO2), RSS value,
      colonoscopy time, total dose of propofol, complications, recovery time, and
      discharge time, as well as colonoscopist and patient satisfaction scores.
      RESULTS: MAP at the 15(th) minute in Group PA was significantly higher than in
      Group PF (p = 0.037). Group PA's beginning mean heart rate was higher than the
      mean heart rate at subsequent readings (p = 0.012, p = 0.002). The mean total
      propofol dose of Group PA was significantly higher than the total dose of Group
      PF (p = 0.028). The mean recovery time of Group PA was significantly longer than
      that of Group PF (p = 0.032). CONCLUSION: Fentanyl provides better operative
      conditions and reduces the need for additional propofol doses. These advantages
      cause a shorter recovery time. Therefore, propofol-fentanyl is superior to the
      propofol-alfentanil for sedation-analgesia in colonoscopy.

PMID- 24565244
TI  - Difficult airway intubation with flexible bronchoscope.
AB  - BACKGROUND AND OBJECTIVE: To describe the efficacy and safety of a flexible
      bronchoscopy intubation (FBI) protocol in patients with difficult airway. METHOD:
      We reviewed the medical records of patients diagnosed with difficult airway who
      underwent flexible bronchoscopy intubation under spontaneous ventilation and
      sedation with midazolam and fentanyl from March 2009 to December 2010. RESULTS:
      The study enrolled 102 patients, 69 (67.7%) men and 33 (32.3%) women, with a mean
      age of 44 years. FBI was performed in 59 patients (57.8%) with expected difficult
      airway in the operating room, in 39 patients (38.2%) in the Intensive Care Unit
      (ICU), and in 4 patients (3.9%) in the emergency room. Cough, decrease in
      transient oxygen saturation, and difficult progression of the cannula through the
      larynx were the main complications, but these factors did not prevent intubation.
      CONCLUSION: FBI according to the conscious sedation protocol with midazolam and
      fentanyl is effective and safe in the management of patients with difficult
      airway.

PMID- 24565245
TI  - Inadvertent venous air embolism during cesarean section: Collapsible intravenous
      fluid bags without self-sealing outlet have risks. Case report.
AB  - The anesthesiologist must be aware of the causes, diagnosis and treatment of
      venous air embolism and adopt the practice patterns to prevent its occurrence.
      Although venous air embolism is a known complication of cesarean section, we
      describe an unusual inattention that causes iatrogenic near fatal venous air
      embolism during a cesarean section under spinal anesthesia. One of the reasons
      for using self-collapsible intravenous (IV) infusion bags instead of conventional
      glass or plastic bottles is to take precaution against air embolism. We also
      demonstrated the risk of air embolism for two kinds of plastic collapsible
      intravenous fluid bags: polyvinyl chloride (PVC) and polypropylene-based. Fluid
      bags without self-sealing outlets pose a risk for air embolism if the closed
      system is broken down, while the flexibility of the bag limits the amount of air
      entry. PVC-based bags, which have more flexibility, have significantly less risk
      of air entry when IV administration set is disconnected from the outlet. Using a
      pressure bag for rapid infusion can be dangerous without checking and emptying
      all air from the IV bag.

PMID- 24565246
TI  - Anesthesia management in a child with osteogenesis imperfecta and epidural
      hemorrhage.
AB  - Osteogenesis Imperfecta (OI) results from gene mutation that causes defective or
      insufficient collagen formation. It may cause various anesthetic complications
      due to the difficulty in airway management, existence of spinal deformity,
      respiratory disorders, cardiac anomalies, thrombocyte function disorder, risk of
      hyperthermia, bacillary invagination, bone deformities and metabolic disorders.
      The anesthesia management of OI patients should be exercised with caution given
      certain risks of respiratory disorders. These risks are due to thorax deformity,
      bone fractures during moving or changing position, mandibular and cervical
      fractures related with intubation, difficult intubation and malignant
      hyperthermia. The anesthetic technique using Total Intravenous Anesthesia (TIVA)
      and laryngeal mask airway is suitable for pediatric patient care with OI.
      However, these techniques have not yet been reported as useful in neurosurgery
      case reports. In this study, we present the use of TIVA and ProSeal Laringeal
      Mask in a child with OI and epidural hemorrhage. We came to the conclusion that
      LMA and TIVA can safely be used in the anesthetic management of OI patients with
      severe anesthetic problems.

PMID- 24565247
TI  - Anesthesia for cesarean section in a patient with Guillain-Barre syndrome: Case
      report.
AB  - BACKGROUND AND OBJECTIVES: Guillain-Barre syndrome during pregnancy is considered
      a rare neurological complication, and there is no consensus in literature for
      anesthetic management for cesarean section in such patients. The objective of
      this paper is to report the case of a pregnant woman with Guillain-Barre syndrome
      undergoing cesarean section. CASE REPORT: Female patient, 22-year old, 35 weeks
      and 5 days of gestation, undergoing cesarean section, hospitalized, reporting
      decreased strength and lower limb paresthesias. Cerebrospinal fluid (CSF)
      analysis showed increased protein (304 mg.dL(-1)) without increased cellularity.
      The anesthetic technique used was general anesthesia induced with propofol (1.5
      mg.kg(-1)) and maintained with 2% sevoflurane in oxygen and fentanyl (3 MUg.kg(
      1)). The procedure was uneventful for both mother and neonate. The patient was
      discharged 10 days after admission, after progressive improvement of neurological
      symptoms. CONCLUSION: The anesthetic technique for pregnant women with Guillain
      Barre syndrome requiring cesarean section remains at the discretion of the
      anesthesiologist, who should be guided by the clinical conditions and
      comorbidities of each patient.

PMID- 24565248
TI  - The dissection of reinforced endotracheal tube internal wall causing
      intraoperative airway obstruction under general anesthesia. Case report.
AB  - Endotracheal intubation is performed to establish a secure airway. However, this
      carries its risks and obstruction of an endotracheal tube (ETT) is a potentially
      life-threatening event. We report two cases with an obstruction of the
      resterilized, single use, spiral, reinforced endotracheal tubes by dissection of
      the internal wall. As a conclusion, we suggest not reusing and resterilizing
      single tubes in these cases to avoid a complication like dissection of the
      internal wall of the tube, as this has been the main cause.

PMID- 24565249
TI  - Cephalic angulation of epidural needle insertion may be an important factor to
      safely approach the epidural space: A mathematical model.

PMID- 24565250
TI  - The harbinger of mortality in heart failure with preserved ejection fraction: do
      GDF-15 levels reflect tandem, deterministic effects of fibrosis and inflammation?

PMID- 24565251
TI  - Impaired cardiac function in metabolic syndrome.

PMID- 24565252
TI  - Specialist heart failure clinics must evolve to stay relevant.
AB  - The widespread acceptance of heart-failure (HF) clinics is based on studies with
      poor and poorly-described care. This led to HF-clinic proliferation, often with
      access for a small percentage of younger, healthier and generally affluent
      patients. This system fails to provide the essential timely access to specialist
      team consultation following hospital-discharge. Recent well-conducted randomized
      trials of HF-clinic care found no benefit over usual care. To provide optimal
      value, HF-clinics must evolve to devote resources to timely
      assessment/reassessment and close follow-up of selected high-risk/advanced HF
      patients, along with timely support of the primary-care team that will assure the
      bulk of routine HF care. 

PMID- 24565253
TI  - A novel approach to drug development in heart failure: towards personalized
      medicine.
AB  - Evidence-based treatment has succeeded in improving clinical outcomes in heart
      failure. Nevertheless, morbidity, mortality, and the economic burden associated
      with the syndrome remain unsatisfactorily high. Most landmark heart failure
      studies included broad study populations, and thus current recommendations
      dictate standardized, universal therapy. While most patients included in recent
      trials benefit from this background treatment, exceeding this already significant
      gain has proven to be a challenge. The early identification of responders and
      nonresponders to treatment could result in improved therapeutic effectiveness,
      while reduction of unnecessary exposure may limit harmful and unpleasant side
      effects. In this review, we examine the potential value of currently available
      information on differential responses to heart failure therapy-a first step
      toward personalized medicine in the management of heart failure. 

PMID- 24565254
TI  - Destination therapy with left ventricular assist devices: for whom and when?
AB  - Historically, cardiac transplantation is the only definitive therapy for
      mortality reduction, symptom reduction, and improved quality of life in advanced
      heart failure. Because of improvement in cardiovascular care there is now a
      growing number of patients such as the elderly and those with abundant
      comorbidity who are not eligible for cardiac transplant. Durable mechanical
      circulatory support is the new reality in the treatment of advanced heart failure
      in this population subset. The left ventricular assist device (LVAD) has evolved
      from humble origins as a short-term extracorporeal and pulsatile device into a
      durable intracorporeal continuous flow device capable of providing permanent
      support in the form of destination therapy (DT) LVAD. Data gathered from original
      landmark clinical trials including Randomized Evaluation of Mechanical Assistance
      for the Treatment of Congestive Heart Failure (REMATCH), and the Heart Mate II
      Trial, and the Interagency Registry for Mechanically Assisted Circulatory Support
      (INTERMACS) provide insight into the type of patient and the timing in which to
      consider DT LVAD therapy. There are a number individual patient warning signs and
      symptoms that predate clinical decline; thus, identifying individuals who might
      benefit from a DT LVAD strategy. The adverse event burden that accompanies DT
      LVAD therapy cannot be ignored when considering LVAD as an adjunct to ongoing
      medical therapy. Trends in patient selection regarding mechanical circulatory
      support continue to evolve along with the technology. As more clinical outcome
      data are gathered we will continue to refine our patient selection criteria and
      timing of implant. 

PMID- 24565255
TI  - Conceptual model for heart failure disease management.
AB  - The objective of this review is to propose a conceptual model for heart failure
      (HF) disease management (HFDM) and to define the components of an efficient HFDM
      plan in reference to this model. Articles that evaluated 1 or more of the
      following aspects of HFDM were reviewed: (1) outpatient clinic follow-up; (2)
      self-care interventions to enhance patient skills; and (3) remote evaluation of
      worsening HF either using structured telephone support (STS) or by monitoring
      device data (telemonitoring). The success of programs in reducing readmissions
      and mortality were mixed. Outpatient follow-up programs generally resulted in
      improved outcomes, including decreased readmissions. Based on 1 meta-analysis,
      specialty clinics improved outcomes and nonspecialty clinics did not. Results
      from self-care programs were inconsistent and might have been affected by patient
      cognitive status and educational level, and intervention intensity.
      Telemonitoring, despite initially promising meta-analyses demonstrating a
      decrease in the number and duration of HF-related readmissions and all-cause
      mortality rates at follow-up, has not been shown in randomized trials to
      consistently reduce readmissions or mortality. However, evidence from device
      monitoring trials in particular might have been influenced by technology and
      design issues that might be rectified in future trials. Results from the
      literature suggest that the ideal HFDM plan would include outpatient follow-up at
      an HF specialty clinic and continuous education to improve patient self-care. The
      end result of this plan would lead to better understanding on the part of the
      patient and improved patient ability to recognize and respond to signs of
      decompensation. 

PMID- 24565256
TI  - Risk stratification in acute heart failure.
AB  - Acute heart failure is a leading reason for emergency department visits, hospital
      admissions, and readmissions. Despite the high rate of hospitalization for heart
      failure and the high resource burden attributable to acute heart failure,
      limitations of clinical decisions have been demonstrated. Risk stratification
      methods might provide guidance to clinicians who care for patients with acute
      heart failure syndromes, and might improve decision-making in emergent care when
      decisions must be made quickly and accurately. Although many acute heart failure
      risk models have been developed in hospitalized cohorts to predict in-hospital
      mortality, there are fewer methods to enable prognostication broadly among all
      patients in a community-based setting. As validated predictive risk algorithms
      become increasingly accessible, they may be applied to select optimal therapies,
      determine how patients will be cared for in the emergency department, and improve
      decisions pertaining to patient disposition and follow-up. 

PMID- 24565257
TI  - Assessing the burden of hospitalized and community-care heart failure in Canada.
AB  - BACKGROUND: The surveillance of heart failure (HF) is currently conducted using
      either survey or hospital data, which have many limitations. Because Canada is
      collecting medical information in administrative health data, the present study
      seeks to propose methods for the national surveillance of HF using linked
      population-based data. METHODS: Linked administrative data from 5 Canadian
      provinces were analyzed to estimate prevalence, incidence, and mortality rates
      for persons with HF between 1996/1997 and 2008/2009 using 2 case definitions: (1)
      1 hospitalization with an HF diagnosis in any field (H_Any) and (2) 1
      hospitalization in any field or at least 2 physician claims within a 1-year
      period (H_Any_2P). One hospitalization with an HF diagnosis code in the most
      responsible diagnosis field (H_MR) was also compared. Rates were calculated for
      individuals aged >= 40 years. RESULTS: In 2008/2009, combining the 5 provinces
      (approximately 82% of Canada's total population), both age-standardized HF
      prevalence and incidence were underestimated by 39% and 33%, respectively, with
      H_Any when compared with H_Any_2P. Mortality was higher in patients with H_MR
      compared with H_Any. The degree of underestimation varied by province and by age,
      with older age groups presenting the largest differences. Prevalence estimates
      were stable over the years, especially for the H_Any_2P case definition.
      CONCLUSIONS: The prevalence and incidence of HF using inpatient data alone likely
      underestimates the population rates by at least 33%. The addition of physician
      claims data is likely to provide a more inclusive estimate of the burden of HF in
      Canada.

PMID- 24565258
TI  - Reduced endoplasmic reticulum stress might alter the course of heart failure via
      caspase-12 and JNK pathways.
AB  - BACKGROUND: Endoplasmic reticulum (ER) stress plays an important role in
      mediating ischemic heart cell death. The aim of this study was to investigate
      whether manipulation of a key factor of the ER stress pathway, eukaryotic
      translation initiation factor 2 subunit alpha (eIF2alpha), can change the natural
      history of heart failure (HF). METHODS: HF was induced using coronary artery
      ligation in adult rats and a selective eIF2alpha dephosphorylation inhibitor,
      salubrinal (Sal), was used. Thirty minutes after ligation, rats were randomly
      assigned to 3 groups: myocardial infarction (MI) plus placebo injections
      (dimethyl sulfoxide; n = 12), MI plus Sal injection (Sal; n = 12), and MI (HF; n
      = 12). Hemodynamic parameters were examined. Hearts were harvested for apoptosis
      assessment after 8 weeks of Sal treatment by terminal deoxynucleotidyl
      transferase deoxyuridine triphosphate nick end labelling and flow cytometric
      analysis. Hearts were harvested to determine ER chaperones by Western analysis,
      real-time polymerase chain reaction and immunohistochemical analysis. RESULTS:
      Cardiac function was significantly improved in Sal-treated rats. Apoptosis was
      reduced by Sal treatment. Glucose-regulated protein-78 and -94 were increased in
      HF but normalized by Sal treatment. HF caused a significant increase in eIF2alpha
      phosphorylation, which was further increased by Sal treatment, and caspase-12 and
      phospho-c-JUN NH2-terminal kinase were markedly increased in rats with HF alone
      but significantly reduced by Sal treatment. CONCLUSIONS: Our results suggest that
      reduction of ER stress and myocardial apoptosis through inhibition of eIF2alpha
      dephosphorylation might alter the natural history of HF, which might provide a
      new approach for its treatment.

PMID- 24565259
TI  - Integrating domain similarity to improve protein complexes identification in TAP
      MS data.
AB  - BACKGROUND: Detecting protein complexes in protein-protein interaction (PPI)
      networks plays an important role in improving our understanding of the dynamic of
      cellular organisation. However, protein interaction data generated by high
      throughput experiments such as yeast-two-hybrid (Y2H) and tandem affinity
      purification/mass-spectrometry (TAP-MS) are characterised by the presence of a
      significant number of false positives and false negatives. In recent years there
      has been a growing trend to incorporate diverse domain knowledge to support large
      scale analysis of PPI networks. METHODS: This paper presents a new algorithm, by
      incorporating Gene Ontology (GO) based semantic similarities, to detect protein
      complexes from PPI networks generated by TAP-MS. By taking co-complex relations
      in TAP-MS data into account, TAP-MS PPI networks are modelled as bipartite graph,
      where bait proteins consist of one set of nodes and prey proteins are on the
      other. Similarities between pairs of bait proteins are computed by considering
      both the topological features and GO-driven semantic similarities. Bait proteins
      are then grouped in to sets of clusters based on their pair-wise similarities to
      produce a set of 'seed' clusters. An expansion process is applied to each 'seed'
      cluster to recruit prey proteins which are significantly associated with the same
      set of bait proteins. Thus, completely identified protein complexes are then
      obtained. RESULTS: The proposed algorithm has been applied to real TAP-MS PPI
      networks. Fifteen quality measures have been employed to evaluate the quality of
      generated protein complexes. Experimental results show that the proposed
      algorithm has greatly improved the accuracy of identifying complexes and
      outperformed several state-of-the-art clustering algorithms. Moreover, by
      incorporating semantic similarity, the proposed algorithm is more robust to
      noises in the networks.

PMID- 24565261
TI  - Luminescence nanothermometry with alkyl-capped silicon nanoparticles dispersed in
      nonpolar liquids.
AB  - Silicon nanoparticles (Si NPs) with a diameter size ranging from 4 to 8 nm were
      successfully fabricated. They exhibit a visible photoluminescence (PL) due to the
      quantum confinement effect. Chemical functionalization of these Si NPs with alkyl
      groups allowed to homogeneously disperse them in nonpolar liquids (NPLs). In
      comparison to most of literature results for Si NPs, an important PL peak
      position variation with temperature (almost 1 meV/K) was obtained from 303 to 390
      K. The influence of the liquid viscosity on the peak positions is also presented.
      These variations are discussed considering energy transfer between nanoparticles.
      The high PL thermal sensitivity of the alkyl-capped Si NPs paves the way for
      their future application as nanothermometers. 

PMID- 24565260
TI  - Clinical applications of neuroimaging in patients with Alzheimer's disease: a
      review from the Fourth Canadian Consensus Conference on the Diagnosis and
      Treatment of Dementia 2012.
AB  - In May 2012, the Fourth Canadian Consensus Conference on the Diagnosis and
      Treatment of Dementia brought together in Montreal experts from around Canada to
      update Canadian recommendations for the diagnosis and management of patients with
      neurodegenerative conditions associated with deterioration of cognition. Multiple
      topics were discussed. The present paper is a highly condensed version of those
      recommendations that were produced to support discussions in the field of
      neuroimaging for clinical diagnosis of those conditions. 

PMID- 24565262
TI  - Rickettsia and vector biodiversity of spotted fever focus, Atlantic rain forest
      biome, Brazil.

PMID- 24565263
TI  - Psychosocial factors and attendance at a population-based mammography screening
      program in a cohort of Swedish women.
AB  - BACKGROUND: A better understanding of the factors that influence mammography
      screening attendance is needed to improve the effectiveness of these screening
      programs. The objective of the study was to examine whether psychosocial factors
      predicted attendance at a population-based invitational mammography screening
      program. METHODS: Data on cohabitation, social network/support, sense of control,
      and stress were obtained from the Malmo Diet and Cancer Cohort Study and linked
      to the Malmo mammography register in Sweden. We analyzed 11,409 women (age 44 to
      72) who were free of breast cancer at study entry (1992 to 1996). Mammography
      attendance was followed from cohort entry to December 31, 2009. Generalized
      Estimating Equations were used to account for repeated measures within subjects.
      Adjusted odds ratios (OR) and 95% confidence intervals (CI) are reported.
      RESULTS: Among 69,746 screening opportunities there were 5,552 (8%) cases of non
      attendance. Higher odds of non-attendance were found among women who lived alone
      (OR = 1.47 (1.33-1.63)) or with children only (OR = 1.52 (1.29-1.81)), had one
      childbirth (OR = 1.12 (1.01-1.24)) or three or more childbirths (OR = 1.34 (1.21
      1.48)), had low social participation (OR= 1.21 (1.10-1.31)), low sense of control
      (OR = 1.12 (1.02-1.23)), and experienced greater stress (OR = 1.24 (1.13-1.36)).
      CONCLUSIONS: Public health campaigns designed to optimize mammography screening
      attendance may benefit from giving more consideration of how to engage with women
      who are less socially involved.

PMID- 24565264
TI  - Theoretical aspects and modelling of cellular decision making, cell killing and
      information-processing in photodynamic therapy of cancer.
AB  - BACKGROUND: The aim of this report is to provide a mathematical model of the
      mechanism for making binary fate decisions about cell death or survival, during
      and after Photodynamic Therapy (PDT) treatment, and to supply the logical design
      for this decision mechanism as an application of rate distortion theory to the
      biochemical processing of information by the physical system of a cell. METHODS:
      Based on system biology models of the molecular interactions involved in the PDT
      processes previously established, and regarding a cellular decision-making system
      as a noisy communication channel, we use rate distortion theory to design a time
      dependent Blahut-Arimoto algorithm where the input is a stimulus vector composed
      of the time dependent concentrations of three PDT related cell death signaling
      molecules and the output is a cell fate decision. The molecular concentrations
      are determined by a group of rate equations. The basic steps are: initialize the
      probability of the cell fate decision, compute the conditional probability
      distribution that minimizes the mutual information between input and output,
      compute the cell probability of cell fate decision that minimizes the mutual
      information and repeat the last two steps until the probabilities converge.
      Advance to the next discrete time point and repeat the process. RESULTS: Based on
      the model from communication theory described in this work, and assuming that the
      activation of the death signal processing occurs when any of the molecular
      stimulants increases higher than a predefined threshold (50% of the maximum
      concentrations), for 1800s of treatment, the cell undergoes necrosis within the
      first 30 minutes with probability range 90.0%-99.99% and in the case of
      repair/survival, it goes through apoptosis within 3-4 hours with probability
      range 90.00%-99.00%. Although, there is no experimental validation of the model
      at this moment, it reproduces some patterns of survival ratios of predicted
      experimental data. CONCLUSIONS: Analytical modeling based on cell death signaling
      molecules has been shown to be an independent and useful tool for prediction of
      cell surviving response to PDT. The model can be adjusted to provide important
      insights for cellular response to other treatments such as hyperthermia, and
      diseases such as neurodegeneration.

PMID- 24565265
TI  - Inferring functional transcription factor-gene binding pairs by integrating
      transcription factor binding data with transcription factor knockout data.
AB  - BACKGROUND: Chromatin immunoprecipitation (ChIP) experiments are now the most
      comprehensive experimental approaches for mapping the binding of transcription
      factors (TFs) to their target genes. However, ChIP data alone is insufficient for
      identifying functional binding target genes of TFs for two reasons. First, there
      is an inherent high false positive/negative rate in ChIP-chip or ChIP-seq
      experiments. Second, binding signals in the ChIP data do not necessarily imply
      functionality. METHODS: It is known that ChIP-chip data and TF knockout (TFKO)
      data reveal complementary information on gene regulation. While ChIP-chip data
      can provide TF-gene binding pairs, TFKO data can provide TF-gene regulation
      pairs. Therefore, we propose a novel network approach for identifying functional
      TF-gene binding pairs by integrating the ChIP-chip data with the TFKO data. In
      our method, a TF-gene binding pair from the ChIP-chip data is regarded to be
      functional if it also has high confident curated TFKO TF-gene regulatory relation
      or deduced hypostatic TF-gene regulatory relation. RESULTS AND CONCLUSIONS: We
      first validated our method on a gathered ground truth set. Then we applied our
      method to the ChIP-chip data to identify functional TF-gene binding pairs. The
      biological significance of our identified functional TF-gene binding pairs was
      shown by assessing their functional enrichment, the prevalence of protein-protein
      interaction, and expression coherence. Our results outperformed the results of
      three existing methods across all measures. And our identified functional targets
      of TFs also showed statistical significance over the randomly assigned TF-gene
      pairs. We also showed that our method is dataset independent and can apply to
      ChIP-seq data and the E. coli genome. Finally, we provided an example showing the
      biological applicability of our notion.

PMID- 24565266
TI  - Usefulness of subclinical left ventricular midwall dysfunction to predict
      cardiovascular mortality in patients with type 2 diabetes mellitus.
AB  - In this study, we tested the hypothesis that impaired midwall shortening predicts
      cardiovascular (CV) mortality in patients with type 2 diabetes mellitus (DM). In
      patients with DM without overt cardiac disease, systolic left ventricular (LV)
      function analyzed by midwall shortening may be impaired although LV ejection
      fraction is preserved. Impaired midwall shortening is an early independent
      prognosticator of adverse clinical outcome in patients with arterial
      hypertension. We analyzed the echocardiographic data from 360 outpatients with DM
      collected during the years 1990 to 2007. Patients had no history or symptoms
      attributable to cardiac disease. Stress-corrected midwall shortening (sc-MS) was
      taken as index of systolic LV function and considered impaired if <89%. The study
      outcome was CV mortality. At baseline, impaired sc-MS was detected in 140
      patients (39%). During a mean follow-up period of 11 years, 54 patients (15%)
      died, 31 (8.6%) of them from CV causes. CV deaths occurred in 21 of 140 patients
      (15%) with impaired sc-MS and in 10 of 220 patients (4.5%) with normal sc-MS
      (p=0.006). Multivariate Cox regression analysis revealed that impaired sc-MS
      (hazard ratio 1.03, 95% confidence interval 1.01 to 1.08, p=0.039), together with
      lower estimated glomerular filtration rate (hazard ratio 0.96, 95% confidence
      interval 0.93 to 0.99, p=0.004), was independently associated with CV mortality
      even after adjustment for age, diabetes duration, hemoglobin A1c, left atrial
      diameter, and heart valve calcium. In conclusion, subclinical systolic LV
      dysfunction as measured by sc-MS occurs frequently in patients with DM without
      overt cardiac disease and independently predicts long-term CV mortality in such
      patients together with lower estimated glomerular filtration rate.

PMID- 24565267
TI  - Optimal conditions to rear phorid parasitoids (Diptera: Phoridae) of Atta
      vollenweideri and Acromyrmex lundii (Hymenoptera: Formicidae).
AB  - Phorid flies have been considered viable options for biological control of leaf
      cutter ants because they are highly specific to these hosts, producing direct
      mortality and also affecting the normal functioning of colonies. Designing
      protocols for mass rearing of these insects requires knowing the temperature and
      humidity conditions that optimize their development in terms of duration,
      survivorship and longevity of adults. We reared Apocephalus setitarsus Brown,
      Eibesfeldtphora trilobata Disney, and Myrmosicarius brandaoi Disney, which are
      specific leaf-cutter ant parasitoids of Atta vollenweideri Forel, and Apocephalus
      neivai Borgmeier and Myrmosicarius catharinensis Borgmeier, which are parasitoids
      of Acromyrmex lundii Guerin-Meneville. Phorids were maintained under one of five
      different rearing conditions, 20 degrees C high humidity (20HH), 24 degrees C low
      and high humidity (24LH and 24HH), and 28 degrees C low and high humidity (28LH
      and 28HH). Flies from all species could complete their development under all the
      conditions tested. As expected, the 20HH treatment significantly lengthened all
      developmental periods in all species, whereas the shortest duration was achieved
      under 28HH. Although pupal survivorship was highest at 24HH, the greatest
      longevity of adults was achieved at 20HH. Percentage of pupae obtained and pupal
      survivorship also exhibited the highest values at 24HH. The rearing efficiency
      index was highest for all species at 24HH. Therefore, we suggest this temperature
      and humidity combination as the most suitable for rearing these species, whereas
      the 20HH treatment is ideal for maintaining adults for longer periods, which
      would be advantageous for synchronizing matings and mass releases of adults in
      the field. 

PMID- 24565268
TI  - Incorporating patient and family preferences into evidence-based medicine.
AB  - BACKGROUND: Clinicians are encouraged to practice evidence-based medicine (EBM)
      as well as patient-centered medicine. At times, these paradigms seem to be
      mutually exclusive and difficult to reconcile. It can become even more
      challenging when trying to include the preferences of the patient's family
      members. This paper discusses the basis for this quandary, providing examples of
      the real-world impact it has on diagnosis-seeking and treatment decision-making
      behaviors and how it might inform implementation of EBM practices. ANALYSIS: To
      further explore the role of friends and family in health-care decision making and
      to understand how patients and families introduce other considerations that may
      or may not be congruent with a strictly EBM approach, data from two research
      studies that examined healthcare-seeking behaviors are presented. Both studies
      explore how family and friends not only can influence health-care decisions but
      also may be a source of conflict for the patient and/or clinician. CONCLUSIONS:
      Illness is a biological and social process. Clinicians who engage in EBM need to
      acknowledge the social and cultural factors that affect the health-care
      encounter, understand the important role of those factors in health-care decision
      making, and expand the paradigm of EBM to incorporate sociocultural influences
      more explicitly. Moreover, recognition of the influences family members and other
      caregivers have within the clinical encounter--by offering opinions and
      participating in treatment-related decision making--is needed and could lead to
      more efficient and effective health care.

PMID- 24565269
TI  - Long-term structured follow-up is essential after curative cancer treatment.

PMID- 24565271
TI  - In reply.

PMID- 24565270
TI  - Breast cancer in young women after treatment for Hodgkin's disease during
      childhood or adolescence--an observational study with up to 33-year follow-up.
AB  - BACKGROUND: The treatment of Hodgkin's disease (HD; also called Hodgkin's
      lymphoma) in children and adolescents with radiotherapy and chemotherapy leads to
      high survival rates but has a number of late effects. The most serious one is the
      development of a secondary malignant tumor, usually in the field that was
      irradiated. In women, breast cancer can arise in this way. METHOD: Data on the
      occurrence of secondary breast cancer (sBC) were collected from 590 women who
      were treated in five consecutive pediatric HD treatment studies in the years 1978
      1995 and then re-evaluated in a late follow-up study after a median interval of
      17.8 years (maximum, 33.7 years). Information was obtained from 1999 onward by
      written inquiry to the participants and their treating physicians. The cumulative
      incidence of sBC was calculated by the Gooley method. RESULTS: By July 2012, sBC
      had been diagnosed in 26 of 590 female HD patients; the breast cancer was in the
      irradiated field in 25 of these 26 patients. Their age at the time of treatment
      for HD was 9.9 to 16.2 years (the pubertal phase), and sBC was discovered with a
      median latency of 20.7 years after HD treatment (shortest latency, 14.3 years)
      and at a median age of 35.3 years (youngest age, 26.8 years). The radiation dose
      to the supradiaphragmatic fields ranged from 20 to 45 Gy. The cumulative
      incidence for sBC 30 years after treatment for HD was 19% (95% confidence
      interval, 12% to 29%). For women aged 25 to 45 in this series, the frequency of
      breast cancer was 24 times as high as in the corresponding normal population.
      CONCLUSION: Women who were treated for HD in childhood or adolescence have an
      increased risk of developing breast cancer as young adults. The risk is
      associated with prior radiotherapy and with the age at which it was administered
      (the pubertal phase). Because of these findings, a structured breast cancer
      screening project for this high-risk group has been initiated in collaboration
      with the German Consortium for Hereditary Breast and Ovarian Cancer (Deutsches
      Konsortium fur familiaren Brust- und Eierstockkrebs).

PMID- 24565272
TI  - The crucial role of molecular diagnostics.

PMID- 24565275
TI  - Incidental venous thromboembolism detected by PET-CT in patients with cancer:
      prevalence and impact on survival rate.
AB  - INTRODUCTION: People with cancer are at increased risk of incidental venous
      thromboembolism (VTE) and PET-CT imaging is commonly used in this population.
      However, the prevalence of incidental VTE detected by PET-CT in patients with
      cancer and its impact on survival are unknown. MATERIALS AND METHODS: This
      retrospective study was approved by the local Institutional Review Board. 1331
      consecutive adult patients with cancer who underwent PET-CT examination between
      2009 and 2012 were included in the study (mean age: 57 +/- 15 years). PET-CT
      reports were reviewed to identify patients with incidental VTE at the time of
      examination. Survival rates were assessed with Kaplan-Meier curves. The Cox
      proportional hazards model was used to determine the association between
      incidental VTE and overall survival, after controlling for clinical variables.
      RESULTS: Incidental VTE was detected in 19 patients (1.4%). Patients with
      genitourinary malignancies, colorectal cancer and lung cancer had the highest
      rates of incidental VTE at PET-CT. At multivariate analysis, incidental VTE
      detected by PET-CT was associated with worse overall survival independently of
      patient age, hospitalization status at time of PET-CT examination, and the
      presence of metastatic disease (Hazard ratio=2.03; 95% confidence interval=1.08
      3.81, p=0.028). CONCLUSION: Incidental VTE was detected in 1.4% of adult patients
      with cancer undergoing PET-CT imaging. Diagnosis of incidental VTE at PET-CT
      imaging was associated with worse overall survival in this population.

PMID- 24565273
TI  - Rhegmatogenous retinal detachment--an ophthalmologic emergency.
AB  - BACKGROUND: Rhegmatogenous retinal detachment is the most common retinological
      emergency threatening vision, with an incidence of 1 in 10 000 persons per year,
      corresponding to about 8000 new cases in Germany annually. Without treatment,
      blindness in the affected eye may result. METHOD: Selective review of the
      literature. RESULTS: Rhegmatogenous retinal detachment typically presents with
      the perception of light flashes, floaters, or a "dark curtain." In most cases,
      the retinal tear is a consequence of degeneration of the vitreous body.
      Epidemiologic studies have identified myopia and prior cataract surgery as the
      main risk factors. Persons in the sixth and seventh decades of life are most
      commonly affected. Rhegmatogenous retinal detachment is an emergency, and all
      patients should be seen by an ophthalmologist on the same day that symptoms
      arise. The treatment consists of scleral buckle, removal of the vitreous body
      (vitrectomy), or a combination of the two. Anatomical success rates are in the
      range of 85% to 90%. Vitrectomy is followed by lens opacification in more than
      70% of cases. The earlier the patient is seen by an ophthalmologist, the greater
      the chance that the macula is still attached, so that visual acuity can be
      preserved. CONCLUSION: Rhegmatogenous retinal detachment is among the main
      emergency indications in ophthalmology. In all such cases, an ophthalmologist
      must be consulted at once.

PMID- 24565274
TI  - All-human microphysical model of metastasis therapy.
AB  - The vast majority of cancer mortalities result from distant metastases. The
      metastatic microenvironment provides unique protection to ectopic tumors as the
      primary tumors often respond to specific agents. Although significant
      interventional progress has been made on primary tumors, the lack of relevant
      accessible model in vitro systems in which to study metastases has plagued
      metastatic therapeutic development--particularly among micrometastases. A real
      time, all-human model of metastatic seeding and cancer cells that recapitulate
      metastatic growth and can be probed in real time by a variety of measures and
      challenges would provide a critical window into the pathophysiology of metastasis
      and pharmacology of metastatic tumor resistance. To achieve this we are advancing
      our microscale bioreactor that incorporates human hepatocytes, human
      nonparenchymal liver cells, and human breast cancer cells to mimic the hepatic
      niche in three dimensions with functional tissue. This bioreactor is instrumented
      with oxygen sensors, micropumps capable of generating diurnally varying profiles
      of nutrients and hormones, while enabling real-time sampling. Since the liver is
      a major metastatic site for a wide variety of carcinomas and other tumors, this
      bioreactor uniquely allows us to more accurately recreate the human metastatic
      microenvironment and probe the paracrine effects between the liver parenchyma and
      metastatic cells. Further, as the liver is the principal site of xenobiotic
      metabolism, this reactor will help us investigate the chemotherapeutic response
      within a metabolically challenged liver microenvironment. This model is
      anticipated to yield markers of metastatic behavior and pharmacologic metabolism
      that will enable better clinical monitoring, and will guide the design of
      clinical studies to understand drug efficacy and safety in cancer therapeutics.
      This highly instrumented bioreactor format, hosting a growing tumor within a
      microenvironment and monitoring its responses, is readily transferable to other
      organs, giving this work impact beyond the liver.

PMID- 24565276
TI  - On control of singleton attractors in multiple Boolean networks: integer
      programming-based method.
AB  - BACKGROUND: Boolean network (BN) is a mathematical model for genetic network and
      control of genetic networks has become an important issue owing to their
      potential application in the field of drug discovery and treatment of intractable
      diseases. Early researches have focused primarily on the analysis of attractor
      control for a randomly generated BN. However, one may also consider how anti
      cancer drugs act in both normal and cancer cells. Thus, the development of
      controls for multiple BNs is an important and interesting challenge. RESULTS: In
      this article, we formulate three novel problems about attractor control for two
      BNs (i.e., normal cell and cancer cell). The first is about finding a control
      that can significantly damage cancer cells but has a limited damage to normal
      cells. The second is about finding a control for normal cells with a guaranteed
      damaging effect on cancer cells. Finally, we formulate a definition for finding a
      control for cancer cells with limited damaging effect on normal cells. We propose
      integer programming-based methods for solving these problems in a unified manner,
      and we conduct computational experiments to illustrate the efficiency and the
      effectiveness of our method for our multiple-BN control problems. CONCLUSIONS: We
      present three novel control problems for multiple BNs that are realistic control
      models for gene regulation networks and adopt an integer programming approach to
      address these problems. Experimental results indicate that our proposed method is
      useful and effective for moderate size BNs.

PMID- 24565279
TI  - Predicting ion specific capacitances of supercapacitors due to quantum ionic
      interactions.
AB  - A new theoretical framework is now available to help explain ion specific
      (Hofmeister) effects. All measurements in physical chemistry show ion
      specificity, inexplicable by classical electrostatic theories. These ignore ionic
      dispersion forces that change ionic adsorption. We explored ion specificity in
      supercapacitors using a modified Poisson-Boltzmann approach that includes ionic
      dispersion energies. We have applied ab initio quantum chemical methods to
      determine required ion sizes and ion polarisabilities. Our model represents
      graphite electrodes through their optical dielectric spectra. The electrolyte was
      1.2 M Li salt in propylene carbonate, using the common battery anions, PF6(-),
      BF4(-) and ClO4(-). We also investigated the perhalate series with BrO4(-) and
      IO4(-). The capacitance C=dsigma/dpsi was calculated from the predicted electrode
      surface charge sigma of each electrode with potential psi between electrodes.
      Compared to the purely electrostatic calculation, the capacitance of a positively
      charged graphite electrode was enhanced by more than 15%, with PF6(-) showing
      >50% increase in capacitance. IO4(-) provided minimal enhancement. The
      enhancement is due to adsorption of both anions and cations, driven by ionic
      dispersion forces. The Hofmeister series in the single-electrode capacitance was
      PF6(-)>BF4(-)>ClO4(-)>BrO4(-)>IO4(-) . When the graphite electrode was negatively
      charged, the perhalates provided almost no enhancement of capacitance, while PF6(
      ) and BF4(-) decreased capacitance by about 15%. Due to the asymmetric impact of
      nonelectrostatic ion interactions, the capacitances of positive and negative
      electrodes are not equal. The capacitance of a supercapacitor should therefore be
      reported as two values rather than one, similar to the matrix of mutual
      capacitances used in multielectrode devices.

PMID- 24565278
TI  - Heterogeneity of late-life depression: relationship with cognitive functioning.
AB  - BACKGROUND: Late-life depression is a heterogeneous disorder, whereby cognitive
      impairments are often observed. This study examines which clinical
      characteristics and symptom dimensions of late-life depression are especially
      impacting on specific cognitive domains. METHODS: Cross-sectional data of 378
      depressed and 132 non-depressed older adults between 60-93 years, from the
      Netherlands Study of Depression in Older adults (NESDO) were used. Depressed
      older adults were recruited from both inpatient and outpatient mental healthcare
      institutes and general practices, and diagnosed according to DSM-IV-TR criteria.
      Multivariable associations were examined with depression characteristics
      (severity, onset, comorbidity, psychotropic medication) and symptom dimensions as
      independent variables and cognitive domains (episodic memory, processing speed,
      interference control, working memory) as dependent variables. RESULTS: Late-life
      depression was associated with poorer cognitive functioning. Within depressed
      participants, higher severity of psychopathology and having a first depressive
      episode was associated with poorer cognitive functioning. The use of tricyclic
      antidepressants, serotonergic and noradrenergic working antidepressants, and
      benzodiazepines was associated with worse cognitive functioning. Higher scores on
      the mood dimension were associated with poorer working memory and processing
      speed, whereas higher scores on a motivational and apathy dimension were
      associated with poorer episodic memory and processing speed. CONCLUSIONS:
      Heterogeneity in late-life depression may lead to differences in cognitive
      functioning. Higher severity and having a first depressive episode was associated
      with worse cognitive performance. Additionally, different domains of cognitive
      functioning were associated with specific symptom dimensions. Our findings on the
      use of psychotropic medication suggest that close monitoring on cognitive side
      effects is needed.

PMID- 24565277
TI  - Single-molecule FRET of protein structure and dynamics - a primer.
AB  - Single-molecule spectroscopy has developed into a widely used method for probing
      the structure, dynamics, and mechanisms of biomolecular systems, especially in
      combination with Forster resonance energy transfer (FRET). In this introductory
      tutorial, essential concepts and methods will be outlined, from the FRET process
      and the basic considerations for sample preparation and instrumentation to some
      key elements of data analysis and photon statistics. Different approaches for
      obtaining dynamic information over a wide range of timescales will be explained
      and illustrated with examples, including the quantitative analysis of FRET
      efficiency histograms, correlation spectroscopy, fluorescence trajectories, and
      microfluidic mixing. 

PMID- 24565280
TI  - Using cascading Bloom filters to improve the memory usage for de Brujin graphs.
AB  - BACKGROUND: De Brujin graphs are widely used in bioinformatics for processing
      next-generation sequencing data. Due to a very large size of NGS datasets, it is
      essential to represent de Bruijn graphs compactly, and several approaches to this
      problem have been proposed recently. RESULTS: In this work, we show how to reduce
      the memory required by the data structure of Chikhi and Rizk (WABI'12) that
      represents de Brujin graphs using Bloom filters. Our method requires 30% to 40%
      less memory with respect to their method, with insignificant impact on
      construction time. At the same time, our experiments showed a better query time
      compared to the method of Chikhi and Rizk. CONCLUSION: The proposed data
      structure constitutes, to our knowledge, currently the most efficient practical
      representation of de Bruijn graphs.

PMID- 24565281
TI  - Detecting protein complexes from active protein interaction networks constructed
      with dynamic gene expression profiles.
AB  - BACKGROUND: Protein interaction networks (PINs) are known to be useful to detect
      protein complexes. However, most available PINs are static, which cannot reflect
      the dynamic changes in real networks. At present, some researchers have tried to
      construct dynamic networks by incorporating time-course (dynamic) gene expression
      data with PINs. However, the inevitable background noise exists in the gene
      expression array, which could degrade the quality of dynamic networkds.
      Therefore, it is needed to filter out contaminated gene expression data before
      further data integration and analysis. RESULTS: Firstly, we adopt a dynamic model
      based method to filter noisy data from dynamic expression profiles. Then a new
      method is proposed for identifying active proteins from dynamic gene expression
      profiles. An active protein at a time point is defined as the protein the
      expression level of whose corresponding gene at that time point is higher than a
      threshold determined by a standard variance involved threshold function.
      Furthermore, a noise-filtered active protein interaction network (NF-APIN) is
      constructed. To demonstrate the efficiency of our method, we detect protein
      complexes from the NF-APIN, compared with those from other dynamic PINs.
      CONCLUSION: A dynamic model based method can effectively filter out noises in
      dynamic gene expression data. Our method to compute a threshold for determining
      the active time points of noise-filtered genes can make the dynamic construction
      more accuracy and provide a high quality framework for network analysis, such as
      protein complex prediction.

PMID- 24565282
TI  - Private and public patients in public hospitals in Australia.
AB  - INTRODUCTION: The nature of the private-public mix in health insurance and in
      health care is a major issue in most health systems. OBJECTIVE: To compare the
      hospitalization characteristics of private and public patients hospitalized in
      public hospitals. METHODS: We focused on planned, overnight and same-day
      admissions, discharged during 2004-2005 from the public New South Wales
      hospitals, and run fixed-effects regressions in order to identify the effect of
      accommodation status (private/public) on the hospitalization characteristics.
      RESULTS: Private patients have one third less waiting days than public patients,
      and they are assigned higher urgency of admission. Length of stay and length of
      visit are both unrelated to the accommodation status, however, private patients
      tend to have more hours in ICU and more procedures performed during the
      hospitalization. In-hospital mortality and the number of transfers (wards) are
      not affected by the accommodation status. CONCLUSIONS: Private patients are
      treated differently than public patients in public hospitals, reinforcing the
      private health insurance-related inequity in inpatient care identified by others.
      Two health policy issues emerge from the findings: the role of private health
      insurance in the Australian socialized medicine system, and in particular, in the
      public hospitals; and the way public hospitals are reimbursed for private
      patients.

PMID- 24565284
TI  - Evaluation of canine and feline leishmaniasis by the association of blood
      culture, immunofluorescent antibody test and polymerase chain reaction.
AB  - BACKGROUND: This study aimed to evaluate the occurrence of Leishmania spp. in
      dogs and cats from Botucatu, Sao Paulo state, and Campo Grande, Mato Grosso do
      Sul state, Brazil, by the association of three diagnostic tests: blood culture in
      liver infusion tryptose medium, immunofluorescent antibody test and polymerase
      chain reaction. Fifty blood samples of dogs and cats from the Center for Zoonosis
      Control in Campo Grande, an area endemic for canine visceral leishmaniasis, were
      collected randomly, as well as canine and feline blood samples from the Municipal
      Kennel and Animal Protection Association in Botucatu, currently considered a
      transmission-free, non-endemic area. RESULTS: Of the 50 dog blood cultures from
      Botucatu, three (6%) were positive and of the 50 cats, two (4%) were positive. In
      Campo Grande, 29 dog blood cultures (58%) were positive and all (100%) cats
      negative by this test. Polymerase chain reaction detected Leishmania spp. in 100%
      of dog and cat samples from Botucatu but found all the cats from Campo Grande to
      be negative. On the other hand, 36 dogs from Campo Grande were positive (72%) by
      the same technique. Immunofluorescent antibody test in Botucatu found 100% of
      dogs and cats non-reactive, while in Campo Grande, it detected positivity in 32
      dogs (64%) and 15 cats (30%). CONCLUSIONS: The results show the importance of not
      only continuous epidemiological surveillance in areas not endemic for
      leishmaniasis, but also research for accurate diagnosis of this zoonosis.

PMID- 24565283
TI  - Optimising the use of mTOR inhibitors in renal transplantation.
AB  - Renal transplantation is the treatment of choice for end-stage renal failure.
      Although advances in immunosuppression have led to improvements in short-term
      outcomes, graft survival beyond 5 to 10 years has not improved. One of the major
      causes of late renal allograft failure is chronic allograft nephropathy, a
      component of which is nephrotoxicity from the use of calcineurin inhibitors
      (CNIs). In addition, premature patient death is a major limitation of renal
      transplantation and the major causes are cancer, cardiovascular disease and
      infection. CNI-free immunosuppressive regimens based on mammalian target of
      rapamycin (mTOR) inhibitors have been trial led over the last few years and have
      defined the rational use of these agents. Conversion from a CNI-based to an mTOR
      inhibitor-based regimen has been successful at improving renal function for a
      number of years after conversion, although long-term survival outcomes are still
      awaited. The studies suggest that the safest and most effective time to convert
      is between 1 and 6 months after transplant. In addition, mTOR-inhibitor-based
      regimens have been shown to be associated with lower rates of post-transplant
      malignancy and less cytomegalovirus infection, which may add further to the
      appeal of this approach. 

PMID- 24565286
TI  - Atypical Streptococcus suis in man, Argentina, 2013.

PMID- 24565287
TI  - Sparse representation approaches for the classification of high-dimensional
      biological data.
AB  - BACKGROUND: High-throughput genomic and proteomic data have important
      applications in medicine including prevention, diagnosis, treatment, and
      prognosis of diseases, and molecular biology, for example pathway identification.
      Many of such applications can be formulated to classification and dimension
      reduction problems in machine learning. There are computationally challenging
      issues with regards to accurately classifying such data, and which due to
      dimensionality, noise and redundancy, to name a few. The principle of sparse
      representation has been applied to analyzing high-dimensional biological data
      within the frameworks of clustering, classification, and dimension reduction
      approaches. However, the existing sparse representation methods are inefficient.
      The kernel extensions are not well addressed either. Moreover, the sparse
      representation techniques have not been comprehensively studied yet in
      bioinformatics. RESULTS: In this paper, a Bayesian treatment is presented on
      sparse representations. Various sparse coding and dictionary learning models are
      discussed. We propose fast parallel active-set optimization algorithm for each
      model. Kernel versions are devised based on their dimension-free property. These
      models are applied for classifying high-dimensional biological data. CONCLUSIONS:
      In our experiment, we compared our models with other methods on both accuracy and
      computing time. It is shown that our models can achieve satisfactory accuracy,
      and their performance are very efficient.

PMID- 24565285
TI  - Role of emerging neuroimaging modalities in patients with cognitive impairment: a
      review from the Canadian Consensus Conference on the Diagnosis and Treatment of
      Dementia 2012.
AB  - The Fourth Canadian Consensus Conference on the Diagnosis and Treatment of
      Dementia (CCCDTD4) was held 3 to 4 May 2012 in Montreal, Quebec, Canada. A group
      of neuroimaging experts were assigned the task of reviewing and summarizing the
      literature on clinical and research applications of different neuroimaging
      modalities in cognitive disorders. This paper summarizes the literature and
      recommendations made to the conference regarding the role of several emerging
      neuroimaging modalities in cognitive disorders. Functional magnetic resonance
      imaging (MRI), magnetic resonance spectroscopy, and diffusion tensor imaging are
      discussed in detail within this paper. Other emergent neuroimaging modalities
      such as positron emission tomography with novel ligands, high-field MRI, arterial
      spin labeling MRI and noncerebral blood flow single-photon emission computerized
      tomography are only discussed briefly. Neuroimaging modalities that were
      recommended at the CCCDTD4 for both clinical and research applications such as
      amyloid and flurodeoxyglucose positron emission tomography, computerized
      tomography and structural MRI are discussed in a separate paper by the same
      authors. A literature search was conducted using the PubMed database including
      articles in English that involved human subjects and covered the period from the
      last CCCDTD publication (CCCDTD3; January 2006) until April 2012. Search terms
      included the name of the specific modality, dementia, Alzheimer's disease, and
      mild cognitive impairment. A separate search used the same parameters but was
      restricted to review articles to identify recent evidence-based reviews. Case
      studies and small case series were not included. Papers representing current
      evidence were selected, reviewed, and summarized, and the results were presented
      at the CCCDTD4 meeting with recommendations regarding the utility of various
      neuroimaging modalities in cognitive disorders. The evidence was graded according
      to the Oxford Centre for Evidence Based Medicine guidelines. Due to the
      limitations of current evidence, the neuroimaging modalities discussed in this
      paper were not recommended for clinical investigation of patients presenting with
      cognitive impairment. However, in the research setting, each modality provides a
      unique contribution to the understanding of basic mechanisms and
      neuropathological markers of cognitive disorders, to the identification of
      markers for early detection and for the risk of conversion to dementia in the at
      risk populations, to the differentiation between different types of cognitive
      disorders, and to the identification of treatment targets and indicators of
      treatment response. In conclusion, for all of the neuroimaging modalities
      discussed in this paper, further studies are needed to establish diagnostic
      utility such as validity, reliability, and predictive and prognostic value. More
      multicenter studies are therefore needed with standardized image acquisition,
      experimental protocols, definition of the clinical population studied, larger
      numbers of participants, and longer duration of follow-up to allow
      generalizability of the results to the individual patient. 

PMID- 24565288
TI  - PPSampler2: predicting protein complexes more accurately and efficiently by
      sampling.
AB  - The problem of predicting sets of components of heteromeric protein complexes is
      a challenging problem in Systems Biology. There have been many tools proposed to
      predict those complexes. Among them, PPSampler, a protein complex prediction
      algorithm based on the Metropolis-Hastings algorithm, is reported to outperform
      other tools. In this work, we improve PPSampler by refining scoring functions and
      a proposal distribution used inside the algorithm so that predicted clusters are
      more accurate as well as the resulting algorithm runs faster. The new version is
      called PPSampler2. In computational experiments, PPSampler2 is shown to
      outperform other tools including PPSampler. The F-measure score of PPSampler2 is
      0.67, which is at least 26% higher than those of the other tools. In addition,
      about 82% of the predicted clusters that are unmatched with any known complexes
      are statistically significant on the biological process aspect of Gene Ontology.
      Furthermore, the running time is reduced to twenty minutes, which is 1/24 of that
      of PPSampler. 

PMID- 24565302
TI  - Comparison between continuous thoracic epidural and paravertebral blocks for
      postoperative analgesia in patients undergoing thoracotomy: Systematic review.
AB  - BACKGROUND AND OBJECTIVE: Thoracotomy is a procedure associated with
      postoperative severe pain. Epidural block (EB) is considered the gold standard
      for its control. Paravertebral block (PVB) is an option for the management of
      postoperative pain. The aim of this study was to evaluate by meta-analyses the
      effectiveness of continuous thoracic epidural and paravertebral blocks for pain
      management after thoracotomy and the incidence of adverse effects. METHOD: The
      study was conducted according to the Preferred Reporting Items for Systematic
      Reviews and Meta-Analyses (PRISMA) protocol. We analyzed primary (postoperative
      pain at rest) and secondary outcomes (urinary retention, nausea, vomiting,
      hypotension). We estimated the weighted mean difference for continuous variables
      and odds ratios for categorical variables. RESULTS: We included eight
      prospective, randomized, controlled studies. Meta-analysis showed no
      statistically significant differences between the two techniques regarding the
      outcomes of postoperative pain at rest at four, eight, 12, 16, 20, 24, 36, and 48
      hours. Incidence of urinary retention was higher in EP group (OR = 7.19, CI95 =
      1.87 to 27.7). The occurrence of hypotension was higher in PVB group (OR = 10.28,
      95 = 2.95 to 35.77). There was no statistically significant difference between
      both groups regarding the outcome nausea/vomiting (OR = 3.00, CI95 = 0.49 to
      18.45). CONCLUSION: There were no statistically significant differences in pain
      relief after thoracotomy between EB and PVB. PVB showed a lower incidence of side
      effects with reduced frequency of urinary retention and hypotension.

PMID- 24565289
TI  - APOE epsilon4 and the risk for Alzheimer disease and cognitive decline in African
      Americans and Yoruba.
AB  - BACKGROUND: There is little information on the association of the APOEe4 allele
      and AD risk in African populations. In previous analyses from the Indianapolis
      Ibadan dementia project, we have reported that APOE epsilon4 increased the risk
      for Alzheimer's disease (AD) in African Americans but not in Yoruba. This study
      represents a replication of this earlier work using enriched cohorts and
      extending the analysis to include cognitive decline. METHODS: In this
      longitudinal study of two community dwelling cohorts of elderly Yoruba and
      African Americans, APOE genotyping was conducted from blood samples taken on or
      before 2001 (1,871 African Americans & 2,200 Yoruba). Mean follow up time was 8.5
      years for African Americans and 8.8 years for Yoruba. The effects of
      heterozygosity or homozygosity of epsilon4 and of the possession of e4 on time to
      incident AD and on cognitive decline were determined using Cox's proportional
      hazards regression and mixed effects models. RESULTS: After adjusting for
      covariates, one or two copies of the APOE epsilon4 allele were significant risk
      factors for incident AD (p < 0.0001) and cognitive decline in the African
      American population (p < 0001). In the Yoruba, only homozygosity for APOE
      epsilon4 was a significant risk factor for AD (p = 0.0002) but not for cognitive
      decline (p = 0.2346), however, possession of an e4 allele was significant for
      both incident AD (p = 0.0489) and cognitive decline (p = 0.0425). CONCLUSIONS: In
      this large longitudinal comparative study, APOE epsilon4 had a significant, but
      weaker, effect on incident AD and on cognitive decline in Yoruba than in African
      Americans. The reasons for these differences remain unclear.

PMID- 24565293
TI  - Supplemental oxygen in elective cesarean section under spinal anesthesia: Handle
      the sword with care.
AB  - BACKGROUND AND OBJECTIVES: We aimed to investigate the effect of 21% and 40%
      oxygen supplementation on maternal and neonatal oxidative stress in elective
      cesarean section (CS) under spinal anesthesia. METHODS: Eighty term parturients
      undergoing elective CS under spinal anesthesia were enrolled in the study. We
      allocated patients randomly to breathe 21% (air group) or 40% (oxygen group)
      oxygen from the time of skin incision until the end of the operation. We
      collected maternal pre- and post-operative and umbilical artery (UA) blood
      samples. Total antioxidant capacity (TAC), total oxidant status (TOS) and the
      oxidative stress index (OSI) were measured. RESULTS: Age, weight, height, parity,
      gestation week, spinal-skin incision time, skin incision-delivery time, delivery
      time, operation time, 1(st) and 5(th) minutes Apgar scores, and birth weight were
      similar between the groups (p > 0.05 for all comparisons). There were no
      differences in preoperative TAC, TOS, or OSI levels between the groups (p > 0.05
      for all comparisons). Postoperative maternal TAC, TOS and OSI levels
      significantly increased in the oxygen group (p = 0.047, < 0.001 and 0.038,
      respectively); umbilical artery TAC levels significantly increased in the oxygen
      group (p = 0.003); and umbilical artery TOS and OSI levels significantly
      increased in the air group (p = 0.02 and < 0.001, respectively). CONCLUSIONS: The
      difference in impact on maternal and fetal oxidative stress of supplemental 40%
      compared to 21% oxygen mandates further large-scale studies that investigate the
      role of oxygen supplementation during elective CS under spinal anesthesia.

PMID- 24565304
TI  - Caryocar brasiliense supercritical CO2 extract possesses antimicrobial and
      antioxidant properties useful for personal care products.
AB  - BACKGROUND: The cosmetic and pharmaceutical industries have an increasing
      interest in replacing synthetic antimicrobials in dermatological products due to
      increased microbial resistance to conventional antimicrobial agents. Pequi
      (Caryocar brasiliense) is a native fruit tree of the Brazilian Cerrado,
      specifically used in cosmetics, in the food industry, and for medicinal purposes.
      Leishmanicidal and antifungal activities have been reported previously. This
      study was designed to evaluate the antimicrobial and antioxidant activities of a
      C. brasiliense extract obtained by supercritical CO2 extraction. METHODS: The
      minimum inhibitory concentrations (MICs) against Escherichia coli, Pseudomonas
      aeruginosa, and Staphylococcus aureus were determined by the classical
      microdilution method. Antiseptic activity against these organisms was evaluated
      by the plate diffusion method. The antioxidant potential of the extract was
      evaluated using a method based on the oxidation of 2,2'-azino-bis(3
      ethylbenzothiazoline-6-sulphonic acid) (ABTS). The extract's chemical profile was
      analyzed for the presence of alkaloids, saponins, anthraquinones, steroids,
      tannins, flavonoids, and phenolic compounds according to standard colorimetric
      methods. RESULTS: The C. brasiliense supercritical CO2 extract exhibits
      antimicrobial activity against all bacteria tested. It also possesses antioxidant
      activity, when compared to a vitamin E standard. CONCLUSIONS: The C. brasiliense
      supercritical CO2 extract may be useful for the development of personal care
      products, primarily for antiseptic skin products that inactivate, reduce,
      prevent, or arrest the growth of microorganisms with the inherent intent to
      mitigate or prevent disease as well as products that minimize damage caused by
      free radicals.

PMID- 24565305
TI  - Making decisions in a complex information environment: evidential preference and
      information we trust.
AB  - BACKGROUND: Informed decision making requires that those individuals making
      health and health-care decisions understand the advantages and disadvantages
      associated with particular health options. Research and theory suggest factors
      that contribute to the decision-making process: data on the likelihood of risks
      and benefits, level of certainty about outcomes, familiarity with the health
      issue, characteristics of information sources and presentation, and patient
      values and beliefs. As the health information environment increases in
      complexity, it becomes important to understand how interactions among information
      sources, family, and friends may affect the processing of health information and
      choices and their alignment with available evidence. ANALYSIS: This paper
      discusses the potential interactions among social networks, information sources
      and evidential preferences for health information as they influence health
      decisions. The role of family and friends who increasingly search for health
      information for others and the potential for information filtering influenced by
      second- or third-party attitudes and preferences is explored. Evidential
      preferences suggestive of the potential value of social math (creatively
      presented statistics) strategies for presenting data, the information-processing
      factors that may make personal experiences, anecdotes and testimonials that are
      often shared within social networks and may exert powerful influences on health
      decisions are examined in this article. CONCLUSIONS: The paper concludes with
      recommendations for revised health-communication practices, health professional
      training to improve patient understanding in the clinical encounter, and
      directions for future research. Simple, direct, and socially relevant
      communications that avoid conflicts with the values and beliefs of the
      individual, as well as those of the family and social network, are recommended.

PMID- 24565306
TI  - Introduction to alcohol studies: 75 years in review (Journal of Studies on
      Alcohol and Drugs, Supplement No. 17).

PMID- 24565307
TI  - The Journal of Studies on Alcohol and Drugs and the Rutgers Center of Alcohol
      Studies: a history of the evolution of alcohol research.
AB  - This article reviews the history of the Journal of Studies on Alcohol and Drugs
      as well as the Rutgers Center of Alcohol Studies. Each has its roots in the Yale
      Laboratory of Applied Physiology and the era shortly after the repeal of National
      Prohibition in the United States. The journal was founded as the Quarterly
      Journal of Studies on Alcohol in 1940 by Howard W. Haggard, M.D., director of the
      Yale Laboratory of Physiology. Alcohol, although not originally the sole focus of
      the laboratory, eventually became the main and then only focus. A Section of
      Alcohol Studies and later Center of Alcohol Studies formally became components of
      the laboratory. The faculty grew to include notable figures such as Elvin Morton
      Jellinek and Mark Keller, among other influential people who helped establish a
      modern, multidisciplinary, scientific approach to alcohol problems in the United
      States. The first alcohol education program, originally called the Summer Session
      of the School of Alcohol Studies, was also founded there in 1943. The center
      later moved to Rutgers University in New Jersey, becoming the Rutgers Center of
      Alcohol Studies in 1962. With it came the summer school and the Quarterly Journal
      of Studies on Alcohol, which in 1975 became the Journal of Studies on Alcohol.
      The journal again changed names in 2007, becoming the Journal of Studies on
      Alcohol and Drugs, reflecting an increasing focus among substance use researchers
      on drugs other than alcohol. This article discusses the influence of the journal
      and the center in the larger historical context of alcohol studies throughout the
      20th century to the modern day.

PMID- 24565308
TI  - A review of studies of drinking patterns in the United States since 1940.
AB  - OBJECTIVE: This article reviews changes in drinking patterns in the general U.S.
      population since the first appearance of the Quarterly Journal of Studies on
      Alcohol in June 1940. METHOD: Contents of the three iterations of the journal
      (Quarterly Journal of Studies on Alcohol, Journal of Studies on Alcohol, and
      Journal of Studies on Alcohol and Drugs) were reviewed along with additional
      prominent key articles on the subject known to the author. RESULTS: Early
      articles in the field tended to focus on alcoholics and alcoholism, usually with
      a biological emphasis. The earliest "scientific investigation" of drinking
      patterns that appeared in iterations of JSAD reported data based on a survey in
      1946, and the earliest report of trends in drinking patterns compared the 1946
      data with data from 1963. Since then, there have been numerous evaluations of
      drinking patterns in the general U.S. population. CONCLUSIONS: There have been
      major changes over the past 75 years in the manner in which drinking patterns are
      measured and summarized. Perhaps the biggest change was the introduction of
      probability sampling. Additional major changes continue to occur, responding to
      technological changes (e.g., the use of computers, cell phones, and broadband
      connections) in how people interact with their environment.

PMID- 24565310
TI  - Culture and alcohol use: historical and sociocultural themes from 75 years of
      alcohol research.
AB  - OBJECTIVE: For the period of almost 75 years, we examined the literature for
      studies regarding the influences of culture on alcohol use and misuse. METHOD:
      This review is a chronology of research articles published from 1940 to 2013.
      From a structured literature search with select criteria, 38 articles were
      identified and 34 reviewed. RESULTS: This analysis revealed a progression across
      this period of research from studies that began as descriptive ethnographic
      evaluations of one or more indigenous societies or cultural groups, evolving to
      studies using complex multivariate models to test cross-cultural effects in two
      or more cultural groups. Major findings across this period include the assertions
      that (a) a function of alcohol use may be to reduce anxiety, (b) certain cultural
      groups possess features of alcohol use that are not associated with negative
      consequences, (c) the disruptive effects of acculturative change and the
      stressors of new demands are associated with an increase in alcohol consumption,
      (d) cultural groups shape expectations about the effects of alcohol use and their
      definition of drunkenness, and (e) the hypothesized relationships of culture with
      alcohol use and misuse have been demonstrated in multivariate model analyses.
      CONCLUSIONS: Across this 75-year period, the early proposition that culture is an
      important and prominent correlate of alcohol use and misuse has persisted. Within
      the current era of alcohol studies, this proposition has been supported by
      multivariate model analyses. Thus, the proposition that culture might affect
      alcohol use remains prominent and is as relevant today as it was when it was
      first proposed nearly 75 years ago.

PMID- 24565309
TI  - College student drinking research from the 1940s to the future: where we have
      been and where we are going.
AB  - OBJECTIVE: College student drinking is not a new phenomenon, yet the field of
      research studying college student drinking is relatively young. In recognition of
      the 75th anniversary of what is now the Journal of Studies on Alcohol and Drugs,
      this article reviews the path from the first article to focus exclusively on
      college student drinking as the topic (published in 1945) to the current state of
      the science and attempts to look forward to the next steps in the field's
      research agenda. METHOD: Articles were selected by consensus of the authors from
      incarnations of the journal and other academic journals based on their relevance
      to the genesis of current best practices regarding college student drinking
      prevention. RESULTS: Major eras and themes include (a) early efforts to describe
      and understand college student drinking; (b) building foundations for prevention
      and intervention efforts in response to growing concerns about high-risk
      drinking; (c) the emergence of harm-reduction efforts, normative interventions,
      and efforts to document campus strategies; (d) efficacious prevention efforts and
      high-risk drinking; (e) the "Call to Action" Task Force Report from the National
      Institute on Alcohol Abuse and Alcoholism; and (f) updates to the science
      (including emerging technology). CONCLUSIONS: Understanding the rich history of
      science related to college drinking prevention should prepare and guide our field
      for the next 75 years of scientific advances, leading to even greater
      understanding of the etiology and topology of college student drinking as well as
      more effective methods to reduce alcohol-related harms.

PMID- 24565311
TI  - Seventy-five years of comorbidity research.
AB  - OBJECTIVE: As part of the 75th anniversary edition of the Journal of Studies on
      Alcohol and Drugs, this article reviews research on the relationship between
      mental disorders and substance use disorders ("comorbidity") from 1940--the
      journal's inception--to the present. METHOD: First, a survey of the titles and
      abstracts of all articles published in the journal was used to identify those
      articles pertaining to comorbidity. Seminal and representative works from this
      set of articles and a limited selection of articles from other journals were
      included in the review. RESULTS: The early psychosocial research emphasized
      psychoanalytic formulations of alcohol use as a defensive symptom, which informed
      the early experimental research on the tension-reducing properties of alcohol.
      The "cognitive revolution," occurring in the 1970s, enabled an expansion of the
      tension-reduction theory to include a central role for mental processes (e.g.,
      alcohol expectancies) in promoting drinking to cope with negative affectivity.
      The early clinical research characterized mental conditions commonly co-occurring
      with alcohol disorders and considered their etiological relationship to alcohol
      disorders. The "neo-Kraepelinian revolution" in psychiatry, which also occurred
      in the 1970s, infused the clinical comorbidity research with a more rigorous
      diagnostic technology and a range of biomedical research methodologies to study
      the mechanistic linkages of co-occurring disorders. CONCLUSIONS: Although a
      substantial quantity of scientific information on comorbidity has accumulated
      over the past 75 years, a standard model(s) of comorbidity has yet to congeal.
      Barriers and opportunities related to achieving this important goal are
      discussed.

PMID- 24565313
TI  - Psychosocial approaches to alcohol use disorders since 1940: a review.
AB  - OBJECTIVE: A review of psychosocial approaches to alcohol use disorders (AUDs)
      was performed to identify and contextualize trends in major treatment approaches
      and special populations and provide possible future directions for alcohol
      research. METHOD: The PsycINFO database was searched for peer-reviewed articles
      relevant to psychosocial approaches to AUDs for each decade since the 1940s,
      resulting in approximately 4,246 articles for review. Topics were included if
      they made up at least 4% of the relevant articles for any one decade. Nine
      treatment and seven special population topics were identified for the current
      review. RESULTS: Psychoanalytic/psychodynamic and aversion therapies were major
      topics in the 1940s and 1950s, but few articles have been published recently.
      Other topics have shown consistent representation in the literature, including
      criminal justice and military populations, self-help groups, group therapies,
      couples and family therapies, behavioral treatments and cognitive-behavioral
      therapy, and complementary/ alternative treatments. The majority of the specific
      population topics and two newer treatment approaches have appeared more recently
      in significant proportions, including adolescents, college students, women,
      ethnic minorities, and dually diagnosed populations; newer treatments include
      brief interventions and motivational interviewing approaches. CONCLUSIONS: The
      number of articles on psychosocial approaches to AUDs has been increasing since
      the 1940s. There have been recent surges in alcohol research on specific
      populations, an increase in the integration of alcohol treatment with primary
      care, and a continued emphasis on empirically supported and cost-effective
      treatments for AUDs; these trends likely will continue into the future.

PMID- 24565312
TI  - A brief history of research on the genetics of alcohol and other drug use
      disorders.
AB  - OBJECTIVE: This article reviews developments in research on genetic influences on
      alcohol and other drug use and disorders over the past 7 decades. METHOD: The
      author began with a review of the flow and content of articles published in the
      three iterations of the journal since 1940 and then used a PubMed search of
      genetics of alcohol and other drug-related topics to gain a broad overview of
      developments in this field. RESULTS: The literature demonstrates the rapid
      metamorphosis of genetic research from the ideas of Mendel to an understanding
      that the substance use disorders are complex, genetically influenced conditions
      where genes explain up to 60% of the picture. Most genes operate through
      additional intermediate characteristics, such as impulsivity and a low
      sensitivity to alcohol, some of which are substance specific and others related
      to substances in general. Using linkage, association, genome-wide association,
      and other modern methods, investigators have identified a diverse range of
      genetic variations that affect substance-related phenomena. CONCLUSIONS: Genetic
      studies regarding alcohol and other drug use and problems have grown dramatically
      in the past 75 years. We currently have a much more sophisticated understanding
      of these influences, and the rapid development of new methods has the promise of
      continuing what has been a solid contribution of important findings in recent
      years.

PMID- 24565315
TI  - Universal prevention for alcohol use disorders: 1940-2014.
AB  - OBJECTIVE: Universal prevention programs are intended to prevent or delay the
      onset of alcohol use disorders in the general population. This article reviews
      research on universal prevention programs for alcohol use published over the last
      75 years. METHOD: A literature search of studies published since the inception of
      the Journal of Studies on Alcohol and Drugs in 1940 revealed 66 manuscripts that
      addressed or reported the findings of universal prevention programs in that
      journal. Additional studies published elsewhere were also reviewed. RESULTS:
      Research on universal prevention programs can be divided into three eras:
      Identifying the need for prevention (1940-1970) and the first (1971-1990) and
      second (1991-2010) eras of universal prevention research. CONCLUSIONS: In the
      past 75 years, the field of universal prevention for alcohol use disorders has
      evolved from nonexistent to mature, replicating and enhancing effective
      strategies and identifying and learning from ineffective ones. The future
      provides unique opportunities to develop sophisticated strategies to enhance the
      efficacy of universal prevention programs.

PMID- 24565314
TI  - Pharmacotherapy of alcohol use disorders: seventy-five years of progress.
AB  - Modern pharmacotherapy for alcohol dependence has its roots in the failure of
      National Prohibition in the United States and the rise of the disease model of
      alcoholism (embodied in Alcoholics Anonymous). In 1948, disulfiram was the first
      medication approved by the U.S. Food and Drug Administration (FDA) to treat
      alcohol dependence, but its efficacy has not been supported by randomized
      controlled trials. In the 1960s, benzodiazepines replaced older treatments for
      alcohol withdrawal, but sedative and dependence-producing effects limit their
      utility in the postwithdrawal period. In the 1980s, the focus shifted to the
      treatment of co-occurring psychiatric disorders and medications that modify
      negative mood states, which contribute to relapse to heavy drinking. In the
      1990s, developments in neurobiology implicated specific neurotransmitter systems
      underlying alcohol's effects, culminating in the 1994 approval by the FDA of the
      opioid antagonist naltrexone to treat alcohol dependence. In 2006, the FDA
      approved a long-acting formulation of naltrexone. Recently, nalmefene, another
      opioid receptor antagonist, was approved in Europe for as-needed use to reduce
      heavy drinking. Acamprosate, an amino acid derivative, first approved in France
      in 1989, received FDA approval in 2004. However, the beneficial effects of the
      approved medications are only modestly greater than those of placebo, and their
      use is limited. Topiramate, currently under investigation for alcohol dependence,
      has greater efficacy but a variety of adverse effects. In addition to the
      identification of novel compounds, the future of alcohol dependence
      pharmacotherapy will depend on developments in pharmacogenetics, in which genetic
      variation that moderates treatment efficacy and adverse effects is used to
      personalize treatment.

PMID- 24565317
TI  - Case closed: research evidence on the positive public health impact of the age 21
      minimum legal drinking age in the United States.
AB  - OBJECTIVE: In 2006, the nonprofit organization Choose Responsibility called for
      repealing the 1984 National Minimum Drinking Age Act, which had led all 50 states
      to establish a minimum legal drinking age (MLDA) of 21 years, and allowing the
      states to lower their MLDA to 18 years. Two years later, the organization
      assembled a small group of college and university presidents (the Amethyst
      Initiative) to call publicly for a critical reexamination of the law. Public
      health and traffic safety experts responded to these efforts by generating new
      research on the age 21 MLDA, thus warranting an updated review of the literature.
      METHOD: This review focuses primarily on research published since 2006, when
      Choose Responsibility began its public relations campaign to lower the MLDA.
      RESULTS: Recent research on the age 21 MLDA has reinforced the position that the
      current law has served the nation well by reducing alcohol-related traffic
      crashes and alcohol consumption among youths, while also protecting drinkers from
      long-term negative outcomes they might experience in adulthood, including alcohol
      and other drug dependence, adverse birth outcomes, and suicide and homicide.
      CONCLUSIONS: The age 21 law saves lives and is unlikely to be overturned. College
      and university leaders need to put into effect workable policies, stricter
      enforcement, and other evidence-based prevention efforts that have been
      demonstrated to reduce underage drinking and alcohol-related problems on campus
      and are being applied successfully at prominent academic institutions.

PMID- 24565318
TI  - Seventy-five years of policy on alcohol problems: an American perspective.
AB  - OBJECTIVE: This article traces the evolution of alcohol-related social policy
      over the past 75 years. METHOD: The literature was reviewed and is critically
      discussed. RESULTS: The social history of alcohol policies over the last 75 years
      began with the scientific approach to alcohol in the 1930s and later shifted to a
      central interest in the disease of alcoholism. Beginning with the National
      Council on Alcoholism Education, advocates struggled to "mainstream" treatment
      for this disease into the health care system. Major steps included
      decriminalization of public intoxication, emphasis of the social respectability
      of persons with alcohol problems, development of a treatment system that was
      accompanied by health insurance coverage, and work-based programs to identify and
      attract employed patients with health insurance coverage. These structures were
      considerably altered by the War on Drugs, managed care, and the merger of drug
      and alcohol treatment. The Affordable Care Act, however, has the potential for
      achieving the mainstreaming goals for alcohol problems originally conceived in
      the early 1940s. CONCLUSIONS: Responsible involvement of the alcoholic beverage
      industry could greatly enhance current activities but is not likely to occur.
      Stigma persists in part because of associations with prevention and treatment of
      illegal drug use problems. The Affordable Care Act offers opportunities and
      challenges to the specialty of treating alcohol use disorders.

PMID- 24565319
TI  - Alcohol studies and science: trapped in the velvet cage of medical research? An
      editorial.
AB  - OBJECTIVE: This article offers the author's assessment of the progress in
      research on alcohol related to alcohol misuse and alcohol use disorders. METHOD:
      The historical background of alcohol-problem research is reviewed in the context
      of defining problems for study and the pattern by which research is funded.
      RESULTS: Progress in terms of cumulative research has been affected by the lack
      of central authority and the National Institutes of Health structure within which
      almost all funding for alcohol research in the United States has occurred.
      Problems are traced to the particular history and nature of alcohol-problem
      research, the continuing prominence of moral elements, and particular features of
      the treatment of alcohol use disorders. CONCLUSIONS: Although the scope of
      activity and production of publications in alcohol research has expanded greatly
      during the past 75 years, there is a potential shortfall in the cumulative
      research that has led to solutions to major problems associated with alcohol.

PMID- 24565316
TI  - A review of alcohol and other drug control policy research.
AB  - OBJECTIVE: This article provides a historical review of alcohol and other drug
      policy research and its impact on public health over the past 75 years. We begin
      our summary with the state of the field circa 1940 and trace the development
      across the subsequent decades. We summarize current thinking and suggest possible
      future directions the field of alcohol and other drug policy may take. Specific
      topics discussed include the minimum legal drinking age, pricing and taxation,
      hours and days of sale, outlet density, and privatization effects. The future of
      drug policy research is also considered. METHOD: A comprehensive search of the
      literature identified empirical studies, reviews, and commentaries of alcohol and
      other drug policy research published from 1940 to 2013 that contributed to the
      current state of the field. RESULTS: Our review demonstrates the historical
      emergence of alcohol problems as a public health issue over the early part of the
      20th century, the public health policy response to this issue, subsequent
      research, and current and future research trends. CONCLUSIONS: Alcohol and other
      drug policy research over the last several decades has made great strides in its
      empirical and theoretical sophistication of evaluating alcohol policy effects.
      This history is not only remarkable for its analytic complexity, but also for its
      conceptual sophistication.

PMID- 24565320
TI  - Quantitative profiling of bacteriocins present in dairy-free probiotic
      preparations of Lactobacillus acidophilus by nanoliquid chromatography-tandem
      mass spectrometry.
AB  - Bacteriocins are a heterogeneous group of ribosomally synthesized peptides or
      proteins with antimicrobial activity, produced predominantly by lactic acid
      bacteria, with potential applications as biopreservatives and probiotics. We
      describe here a novel strategy based on a bottom-up, shotgun proteomic approach
      using nanoliquid chromatography-tandem mass spectrometry (nanoLC-MS/MS) with
      multiple fragmentation techniques for the quantitative profiling of bacteriocins
      present in the probiotic preparations of Lactobacillus acidophilus. A direct LC
      MS/MS analysis with alternate collision-induced dissociation, high-energy
      collision dissociation, and electron-transfer dissociation fragmentation
      following a filter-assisted size-exclusion sample prefractionation has resulted
      in the identification of peptides belonging to 37 bacteriocins or related
      proteins. Peptides from lactacin F, helveticin J, lysin, avicin A, acidocin M,
      curvaticin FS47, and carocin D were predominant. The process of freeze drying
      under vacuum was observed to affect both the diversity and abundance of
      bacteriocins. Data acquisition using alternating complementary peptide
      fragmentation modes, especially electron-transfer dissociation, has significantly
      enhanced the peptide sequence coverage and number of bacteriocin peptides
      identified. Multi-enzyme proteolytic digestion was observed to increase the
      sample complexity and dynamic range, lowering the chances of detection of low
      abundant bacteriocin peptides by LC-MS/MS. An analytical platform integrating
      size exclusion prefractionation, nanoLC-MS/MS analysis with multiple
      fragmentation techniques, and data-dependent decision tree-driven bioinformatic
      data analysis is novel in bacteriocin research and suitable for the comprehensive
      bioanalysis of diverse, low-abundant bacteriocins in complex samples. 

PMID- 24565321
TI  - Improving corn silage quality in the top layer of farm bunker silos through the
      use of a next-generation barrier film with high impermeability to oxygen.
AB  - This study examined the effect on the fermentation, chemical, and microbiological
      quality of corn silage covered with a new-generation high oxygen barrier film
      (HOB) made with a special grade of ethylene-vinyl alcohol (EVOH) compared with a
      standard polyethylene film (PE). Two bunkers (farms 1 and 2) were divided into 2
      parts lengthwise so that half of the silo would be covered with PE film and the
      other with HOB film. Plastic net bags with fresh chopped corn were buried in the
      upper layer (close to and far from the wall) and in the central part of the
      bunkers. During spring-summer consumption, the bags were unloaded, weighed, and
      subsampled to analyze the dry matter (DM) content, neutral detergent fiber and
      starch contents, pH, lactic and monocarboxylic acids, yeast and mold counts,
      aerobic and anaerobic spore-former counts, and aerobic stability. We also
      determined the economic benefit of applying the novel covering. The top layer of
      silage conserved under the HOB film had a higher lactic acid content and lower
      pH; lower counts of yeasts, molds, and aerobic and anaerobic spore-formers;
      higher aerobic stability; and lower DM losses than the silage conserved under the
      PE film. The use of the HOB film prevented almost all of the silage in the upper
      layer from spoiling; only 2 out of 32 samples had a mold count >6log10 cfu/g.
      This led to a net economic gain when the HOB film was used on both farms due to
      the increased DM recovery and reduced labor time required to clean the upper
      layer, even though the HOB film cost about 2.3 times more than the PE film.
      Furthermore, use of the HOB film, which ensures a longer shelf life of silage
      during consumption, reduced the detrimental effect of yeasts, molds, and aerobic
      and anaerobic spore-formers on the nutritional and microbiological quality of the
      unloaded silage. 

PMID- 24565322
TI  - A dynamic mechanistic model of lactic acid metabolism in the rumen.
AB  - Current feed evaluation systems for ruminants are too imprecise to describe diets
      in terms of their acidosis risk. The dynamic mechanistic model described herein
      arises from the integration of a lactic acid (La) metabolism module into an
      extant model of whole-rumen function. The model was evaluated using published
      data from cows and sheep fed a range of diets or infused with various doses of
      La. The model performed well in simulating peak rumen La concentrations
      (coefficient of determination = 0.96; root mean square prediction error = 16.96%
      of observed mean), although frequency of sampling for the published data
      prevented a comprehensive comparison of prediction of time to peak La
      accumulation. The model showed a tendency for increased La accumulation following
      feeding of diets rich in nonstructural carbohydrates, although less-soluble
      starch sources such as corn tended to limit rumen La concentration. Simulated La
      absorption from the rumen remained low throughout the feeding cycle. The
      competition between bacteria and protozoa for rumen La suggests a variable
      contribution of protozoa to total La utilization. However, the model was unable
      to simulate the effects of defaunation on rumen La metabolism, indicating a need
      for a more detailed description of protozoal metabolism. The model could form the
      basis of a feed evaluation system with regard to rumen La metabolism. 

PMID- 24565323
TI  - Hot topic: Brown marmorated stink bug odor compounds do not transfer into milk by
      feeding bug-contaminated corn silage to lactating dairy cattle.
AB  - Brown marmorated stink bug (BMSB; Halyomorpha halys) is an emerging invasive
      species of grave concern to agriculture as a polyphagous plant pest with
      potential negative effects on the dairy industry. The purpose of this study was
      to determine the risk of including BMSB-contaminated silage in lactating dairy
      cow rations. First, 6 dairies, either highly infested (n=3; 30 to 100 bugs per
      stalk) or not infested (n=3), were sampled to assess the prevalence of bug
      secretion compounds tridecane (major component) and E-2-decenal (stink odor
      component) in silage and milk. Second, using wild BMSB, a mini-silo dose-response
      experiment (adding 100, 50, 25, 10, and 1 freshly crushed bugs/0.5kg of chopped
      corn) was conducted to assess the effect of ensiling on BMSB stink odor
      compounds. Finally, synthetic BMSB stink odor compounds (10g of tridecane and 5g
      of E-2-decenal) were ruminally infused twice daily over 3 d, and samples of milk,
      urine, and rumen fluid were collected to evaluate disposition. Bug stink odor
      compounds were sampled by solid-phase microextraction (SPME) and analyzed by gas
      chromatography-mass spectrometry (GC-MS). Milk production and feed composition
      were unaffected when BMSB-contaminated silage was fed. Moreover, no E-2-decenal
      was detected in silage or milk (detection threshold = 0.00125MUg/mL). The dose
      response of tridecane in mini-silo samples exhibited a linear relationship
      (R(2)=0.78) with the amount of BMSB added; however, E-2-decenal was completely
      decomposed and undetectable in spiked mini-silos after ensiling. Both synthetic
      secretion compounds infused into rumen were undetectable in all milk and urine
      samples. E-2-Decenal was not detectable in rumen fluid, whereas tridecane was
      detected only at 15 min postinfusion but not present thereafter. Feed intake was
      unaffected by infusion treatment and BMSB secretion compounds (E-2-decenal and
      tridecane) were not observed in milk. E-2-Decenal and tridecane from the
      metathoracic gland of BMSB are not able to contaminate milk either due to the
      ensiling process or because of metabolism within the rumen. Concern over BMSB
      stink odor compounds contaminating the fluid milk supply, even on highly infested
      farms, is not warranted. 

PMID- 24565324
TI  - Short communication: effects of systemic treatment with penethamate hydriodide on
      udder health and milk yields in dry primiparous Mediterranean buffaloes (Bubalus
      bubalis).
AB  - The effects of penethamate hydriodide (Mamyzin, Boehringer Ingelheim, Ingelheim,
      Germany) on udder health and milk yields were evaluated in primiparous
      Mediterranean buffaloes (Bubalus bubalis). An intramuscular administration of 10
      million international units was performed in 20 buffaloes at 7 d precalving
      (treatment group; TG), and 20 animals were enrolled as the control group (CG).
      Evening milk samplings were performed at 10, 30, and 60 d in milk (DIM). Somatic
      cell count (SCC) values were evaluated on composite milk samples, whereas
      bacteriological culture and California Mastitis Test were performed on quarter
      milk. Daily milk yields were recorded after all milkings. After 60 DIM, composite
      milk samples from each animal were collected for monthly SCC and bacteriological
      culture until drying off. Statistically significant differences were found
      between the prevalence of mastitic quarters in the 2 groups at 10 and 30 DIM, and
      between the incidence of mastitic animals during the examined period (TG: 4/20,
      20% vs. CG: 10/20, 50%). Even though lower and higher values of SCC and milk
      yields were found in TG during each sampling, statistically significant
      differences were only found at 30 (SCC) and 60 DIM (milk yields). In our study,
      the antibiotic administration precalving showed good bactericidal activity
      against the most common udder-specific pathogens that cause mastitis in
      primiparous Mediterranean buffaloes, and greater efficacy was observed at 10 and
      30 DIM compared with 60 DIM. Given the significant decrease in SCC and increase
      in yields achieved, use of this antibiotic could be economically beneficial in
      buffalo breeding. 

PMID- 24565325
TI  - Immunization against gonadotropin-releasing hormone in dairy cattle: antibody
      titers, ovarian function, hormonal levels, and reversibility.
AB  - Suppression of cyclic activity in cattle is often desired in alpine farming and
      for feedlot cattle not intended for breeding. A cattle-specific anti-GnRH
      vaccination (Bopriva, Zoetis Australia Ltd., West Ryde, Australia) is approved
      for use in heifers and bulls in New Zealand, Australia, Mexico, Brazil,
      Argentina, Turkey, and Peru. Eleven healthy, cyclic Swiss Fleckvieh cows were
      included in the study and vaccinated twice with Bopriva 4wk apart. Injection
      site, rectal body temperature, and heart and respiratory rates were recorded
      before and 3d following each vaccination. Blood samples were taken weekly for
      progesterone and estrogen analysis and to determine GnRH antibody titer. Ovaries
      were examined weekly, using ultrasound to count the number of follicles and
      identify the presence of a corpus luteum. Thirty weeks after the first
      vaccination, the cows were subjected to a controlled internal drug-releasing
      device-based Select-Synch treatment. The GnRH antibody titers increased after the
      second vaccination and peaked 2wk later. Estrogen levels were not influenced by
      vaccination, and progesterone level decreased in 7 of 11 cows up to 3wk after the
      second vaccination and remained low for 10 to 15wk following the second
      vaccination. The number of class I follicles (diameter <=5mm) was not influenced
      by vaccination, whereas the number of class II follicles (diameter 6-9mm)
      decreased between 7 and 16wk after the first vaccination. Class III follicles
      (diameter >9mm) were totally absent during this period in most cows. The median
      period until recurrence of class III follicles was 78d from the day of the second
      vaccination (95% confidence interval: 60-92d). After vaccination, all cows showed
      swelling and pain at the injection site, and these reactions subsided within 2wk.
      Body temperature and heart and respiratory rates increased after the first and
      second vaccinations and returned to normal values within 2d of each vaccination.
      The cows in our study were not observed to display estrus behavior until 30wk
      after the first vaccination. Therefore, a Select-Synch protocol was initiated at
      that time. Ten cows became pregnant after the first insemination (the remaining
      cow was reinseminated once until confirmed pregnancy). Bopriva induced a reliable
      and reversible suppression of reproductive cyclicity for more than 2mo. The best
      practical predictor for the length of the anestrus period was the absence of
      class III follicles. 

PMID- 24565326
TI  - Mechanics of proteins with a focus on atomic force microscopy.
AB  - The capacity of proteins to function relies on a balance between molecular
      stability to maintain their folded state and structural flexibility allowing
      conformational changes related to biological function. Among many others, four
      different examples can be chosen. The giant protein titin is stretched and can
      unfold during muscle contraction providing passive elasticity to muscle tissue;
      myoglobin adsorbs and releases oxygen molecules thank to conformational changes
      in its structure; the outer membrane protein G (OmpG) is a bacterial porin with a
      long and flexible loop that modulates gating; and the proton pump
      bacteriorhodopsin adapts its cytosolic half to allow proton pumping. All these
      conformational changes triggered either by chemical or by physical cues, require
      mechanical flexibility or elasticity of certain protein domains. While the
      methods to determine protein structure, X-ray crystallography above all, have
      been dramatically improved over the last decades, the number of tools that
      directly measure the mechanical flexibility of proteins and protein domains is
      still limited. In this tutorial, after a brief introduction to protein structure,
      we present some of the available techniques to estimate protein flexibility, then
      focusing on atomic force microscopy (AFM). We describe the principles of the
      technique and its various imaging and force spectroscopy modes of operation that
      allow probing the elasticity of proteins, protein domains and their surrounding
      environment. 

PMID- 24565327
TI  - Localization of apoptotic and proliferating cells and mRNA expression of caspases
      and Bcl-2 in gonads of chicken embryos.
AB  - The aim of the present study was to analyze participation of apoptosis and
      proliferation in gonadal development in the chicken embryo by: (1) localization
      of apoptotic (TUNEL) and proliferating (PCNA immunoassay) cells in male and
      female gonads and (2) examination of mRNA expression (RT-PCR) of caspase-3,
      caspase-6 and Bcl-2 in the ovary and testis during the second half of
      embryogenesis and in newly hatched chickens. Apoptotic cells were found in gonads
      of both sexes. At E18 the percentage of apoptotic cells (the apoptotic index, AI)
      in the ovarian medulla and the testis was lower (p<0.05) than in the ovarian
      cortex. In the ovarian medulla, the AI at E18 was lower (p<0.05) than on E12. In
      the testis, the AI was significantly lower (p<0.05) at E18 than at E15 and 1D.
      The percentage of proliferating cells (the proliferation index: PI) within the
      ovary significantly increased from E15 to 1D in the cortex, while proliferating
      cells in the medulla were detected only at E15. In the testis, the PI gradually
      increased from E12 to 1D. The mRNA expression of caspase-3 and -6 as well as Bcl
      2 was detected in male and female gonads at days 12 (E12), 15 (E15) and 18 (E18)
      of embryogenesis and the day after hatching (1D). The expression of all analyzed
      genes on E12 was significantly higher (p<0.05) in female than in male gonads.
      This difference was also observed at E15 and E18, but only for the caspase-6. The
      results obtained showed tissue- and sex-dependent differences in the number of
      apoptotic and proliferating cells as well as mRNA expression of caspase-3, -6 and
      Bcl-2 genes in the gonads of chicken embryos. Significant increase in the number
      of proliferating cells in the ovarian cortex and lack of these cells in the
      ovarian medulla (stages E12, E18, 1D) simultaneous with decrease in the intensity
      of apoptosis only in the medulla indicates that proliferation is the dominant
      process involved in the cortical development, which constitutes the majority of
      the functional structure of the fully developed ovary. No pronounced changes in
      the expression of apoptosis-related genes found during embryogenesis suggest that
      they cannot be considered as important indicators of gonad development. The
      molecular mechanisms of the regulation of balance between apoptosis and
      proliferation in developing avian gonads need to be further investigated. 

PMID- 24565328
TI  - Case report: atypical fungal obstruction of the left ventricular assist device
      outflow cannula.
AB  - We describe a very rare case of outflow cannula obstruction with fungal
      infectious thrombus formation. Discussion includes the etiology, diagnosis, and
      management of fungal infection complications related with long-term mechanical
      circulatory support. Left ventricular assist devices (LVADs) are increasingly
      used as bridge to transplant and permanent long-term therapy in the population
      with end-stage heart failure. Even though better clinical outcomes have been
      achieved with the newer-generation continuous-flow devices, infection
      complications are still a major risk for patients with continuous-flow LVAD
      implantation in long-term follow-up [Ann Thorac Surg 90:1270-1277, 2010]. Device
      related infections can be categorized as driveline infections, pump-pocket
      infections, and LVAD-associated endocarditis [Expert Rev Med Devices 8: 627-634,
      2011]. The microbiological profile is very heterogeneous; the most common
      pathogens are Staphylococcus, Pseudomonas, Streptococcus species, and Candida.
      Severe fungal infection may lead to dysfunction of the LVAD due to obstructive
      mass formation within the device. Due to the only anecdotal reports in the
      current literature, we present a very rare case of outflow fungal infectious
      thrombus formation leading to outflow cannula obstruction in patient with LVAD. 

PMID- 24565329
TI  - Job satisfaction of professional Irish dancers: implications for performer health
      and well-being.
AB  - This study investigates for the first time whether experienced former and current
      professional Irish dancers (PIDs) would recommend a career in Irish dance, and
      their perceived positive and negative attitudes toward this occupation. One
      hundred and sixty-five (71 current, 94 retired) PIDs participated in an online
      survey. Additional focus group interviews of six current and three retired PIDs
      were conducted to validate survey findings. PID comments were examined
      independently by the two investigators using thematic analysis and then cross
      indexed and coded into the most common positive and negative themes. Ninety-four
      percent of surveyed PIDs and 100% of focus group participants stated that they
      would recommend a career in professional Irish dance. The main positive
      attributes identified included the opportunity to travel and experience diverse
      cultures, the development of enduring friendships, the pursuit of a hobby as a
      financially lucrative career, evolving personal life skills, and the maintenance
      of good physical health and fitness. The main negative themes included the
      insecure and short-term nature of the career, physical consequences in terms of
      pain and injury, potentially damaging psychological consequences, and practical
      difficulties inherent in a touring lifestyle. The effects of dancer job
      satisfaction on health, wellbeing, and performance are discussed, and
      recommendations for company managers and dance captains are developed based on
      findings. 

PMID- 24565330
TI  - Injury in professional Irish dancers.
AB  - Despite the evolution of Irish dance to professional status in recent decades,
      only scant investigation of musculoskeletal pain and injury among professional
      Irish dancers (PIDs) has been undertaken. This study investigated the rate of
      injury and associated factors among 178 PIDs, using an online questionnaire. One
      hundred and thirty-seven PIDs (76.7%) reported a previous injury, with the foot
      (67.9%) and ankle (60.6%) most commonly affected. A mean career rate of 2.25
      injuries per dancer was computed. The majority of injuries were minor in nature,
      and almost half occurred midway through a tour. Sixty subjects (33.7%) reported
      that they often or always danced in pain. The main contributory factors to injury
      were accidents, fatigue or overwork, repetitive movements, and unsafe stages.
      Warm-up (98.8%) and cool-down (84.3%) were almost universally practised, with
      cross-training engaged in by 124 PIDs (74.7%). Popular treatments used to prevent
      and manage injuries were massage (N = 137, or 83.0% of PIDs), stretching (N =
      117, or 70.1%) and physiotherapy (N = 105, or 62.9%). There was a moderate level
      of psychological distress among the participants, with "interpersonal
      difficulties" and "tension with people" the main problems cited. PIDs who were
      older (p = 0.008) and more experienced (p = 0.002) reported missing a greater
      number of performances due to injury. There were no other significant
      relationships between injury and factors, including gender, frequency of dancing
      in pain, use of warm-up, cool-down, or cross-training. Further prospective
      studies of PIDs should consider both physical and biopsychosocial elements to
      generate an appropriate screening process to predict those at risk of injury. 

PMID- 24565331
TI  - Injuries in Irish dance.
AB  - Irish dance is growing in popularity and competitiveness; however, very little
      research has focused specifically on this genre of dance. The purpose of this
      study was to analyze the types of dance injuries incurred by Irish dancers. A
      chart review was performed to identify all injuries associated with Irish dance
      seen in the sports medicine or orthopaedic clinics at the investigators' hospital
      over an 11-year period. "Injury" was defined as any dance-related pain or
      disorder that led to evaluation in the clinics. Survey data were also collected
      from study participants. Ultimately, 255 patients from over 30 different schools
      of dance were seen with injuries directly related (726 clinic visits) or
      partially related (199 visits) to Irish dance. Participants ranged in age from 4
      to 47, with 95% (243/255) under the age of 19. These 255 patients received 437
      diagnoses. Almost 80% of the injuries (348/437) were attributable to overuse, and
      20.4% were acute and traumatic injuries (89/437). Ninety-five percent (95.9%) of
      injuries involved the hip or lower extremity. The most common sites were the foot
      (33.2%), ankle (22.7%), knee (19.7%), and hip (14.4%). Typical diagnoses were
      tendon injury (13.3%), apophysitis (11.4%), patellofemoral pain and instability
      (10.8%), stress injury (10.1%), and muscle injury (7.8%). The majority of
      traumatic injuries were seen in clinic within 3 weeks, but less than a quarter of
      overuse injuries were seen that quickly. The most common treatment, prescribed to
      84.3% of patients, was physical therapy and home exercises, and the majority of
      dancers (64.3%) were able to return to full dance activity after injury. 

PMID- 24565332
TI  - Performance on the Star Excursion Balance Test predicts functional turnout angle
      in pre-pubescent female dancers.
AB  - The purpose of this study was to determine if there was a predictive relationship
      between performance on the Star Excursion Balance Test (SEBT) and functional
      turnout angle (FTA) in prepubescent female dancers. Ten dance students, ages 5 to
      9 years (mean: 7.3 years), were recruited for this study. The SEBT required the
      subject to reach in the anterior, posterior-medial, and posteriorlateral
      directions with her free-limb foot while standing on the reference limb. A
      composite reach score was determined by calculating the sum of distance reached
      in the three directions and normalizing to leg length. The FTA was assessed in
      first position by measuring the angle of bisection between the second and third
      metatarsals and the midpoint of the calcaneus. Linear regression was used to
      determine if there was a predictive relationship between performance on the SEBT
      and FTA in this cohort. The subjects demonstrated a mean FTA of 90.3 degrees  +/-
      17.7 degrees . Composite reach on the dominant limb normalized to leg length
      (81.4 +/- 11.1%) during the SEBT was a significant predictor of FTA (r(2) = 0.49,
      p = 0.02), while performance on the non-dominant limb (81.9 +/- 10.8%) indicated
      a trend toward a predictive association (r(2) = 0.35, p = 0.07). A decreased
      composite reach score was predictive of decreased FTA. These measurements may
      serve as an important screening tool for identifying dancers at risk for lower
      extremity injury. 

PMID- 24565333
TI  - Spinous process apophysitis: a cause of low back pain following repetitive
      hyperextension in an adolescent female dancer.
AB  - We report a case of a 13-year-old female dancer with spinous process apophysitis
      following repetitive microtrauma during end-range hyperextension movements.
      Following appropriate rest and limitation of hyperextension, she was able to
      return to her previous level of training. It is important to recognize that
      numerous diagnostic possibilities arise when presented with a young dancer with
      back pain. The intention of this case report is to compare and contrast the
      pertinent clinical and radiologic findings of spinous process apophysitis and its
      more common and debilitating mimic, spondylolysis. The correct diagnosis is
      paramount in cases of this sort due to the variable treatment requirements of
      each disorder. 

PMID- 24565334
TI  - A study of the prescription and administration of sedative PRN medication to
      older adults at a secure hospital.
AB  - BACKGROUND: There is a paucity of research into PRN medication use in older
      psychiatric inpatients. This is an important topic given the risks of
      polypharmacy, adverse drug reactions, and high dose medication. METHOD: In 2013,
      we carried out a cross-sectional survey of the prescription and administration of
      sedative PRN medication to older adult inpatients on seven wards at a UK tertiary
      referral centre. We compared them with 242 patients of working age. RESULTS: Of
      the 92 patients studied, 56 (60.9%) were prescribed PRN sedation and 25 (27.2%)
      had received one or more doses in the previous fortnight. In total, 70 doses had
      been administered; all by mouth and all but one as single doses. Lorazepam was by
      far the most commonly prescribed and administered PRN drug. Agitation was the
      main indication, although violence was the most commonly cited reason for
      administration but documentation of antecedents, non-pharmacological strategies
      and outcome including side effects was uniformly poor with only 37 (52.9%) doses
      recorded in the case notes. Those with organic disorders were just as likely to
      receive PRN as those with functional illnesses. Patients very rarely actually
      received high dose antipsychotics or antipsychotic polypharmacy as a result of
      PRN prescriptions. Older patients were less likely than adults of working age to
      be prescribed PRN and dosages were smaller. CONCLUSION: Prospective studies of
      PRN prescription and administration are needed to better understand the reasons
      underpinning its use and to gain objective data upon its effectiveness or
      otherwise in this vulnerable patient group.

PMID- 24565335
TI  - Mathematical modeling of GATA-switching for regulating the differentiation of
      hematopoietic stem cell.
AB  - BACKGROUND: Hematopoiesis is a highly orchestrated developmental process that
      comprises various developmental stages of the hematopoietic stem cells (HSCs).
      During development, the decision to leave the self-renewing state and selection
      of a differentiation pathway is regulated by a number of transcription factors.
      Among them, genes GATA-1 and PU.1 form a core negative feedback module to
      regulate the genetic switching between the cell fate choices of HSCs. Although
      extensive experimental studies have revealed the mechanisms to regulate the
      expression of these two genes, it is still unclear how this simple module
      regulates the genetic switching. METHODS: In this work we proposed a mathematical
      model to study the mechanisms of the GATA-PU.1 gene network in the determination
      of HSC differentiation pathways. We incorporated the mechanisms of GATA switch
      into the module, and developed a mathematical model that comprises three genes
      GATA-1, GATA-2 and PU.1. In addition, a novel multiple-objective optimization
      method was designed to infer unknown parameters in the proposed model by
      realizing different experimental observations. A stochastic model was also
      designed to describe the critical function of noise, due to the small copy
      numbers of molecular species, in determining the differentiation pathways.
      RESULTS: The proposed deterministic model has successfully realized three stable
      steady states representing the priming and different progenitor cells as well as
      genetic switching between the genetic states under various experimental
      conditions. Using different values of GATA-1 synthesis rate for the GATA-1
      protein availability in the chromatin sites during the time period of GATA
      switch, stochastic simulations for the first time have realized different
      proportions of cells leading to different developmental pathways under various
      experimental conditions. CONCLUSIONS: Mathematical models provide testable
      predictions regarding the mechanisms and conditions for realizing different
      differentiation pathways of hematopoietic stem cells. This work represents the
      first attempt at using a discrete stochastic model to realize the decision of HSC
      differentiation pathways showing a multimodal distribution.

PMID- 24565336
TI  - A human pluripotent stem cell platform for assessing developmental neural
      toxicity screening.
AB  - A lack of affordable and effective testing and screening procedures mean
      surprisingly little is known about the health hazards of many of the tens of
      thousands of chemicals in use in the world today. The recent rise in the number
      of children affected by neurological disorders such as autism has stirred
      valuable debate about the role chemicals play in our daily life, highlighting the
      need for improved methods of assessing chemicals for developmental neural
      toxicity. 

PMID- 24565338
TI  - Identifying protein complexes with fuzzy machine learning model.
AB  - BACKGROUND: Many computational approaches have been developed to detect protein
      complexes from protein-protein interaction (PPI) networks. However, these PPI
      networks are always built from high-throughput experiments. The presence of
      unreliable interactions in PPI network makes this task very challenging. METHODS:
      In this study, we proposed a Genetic-Algorithm Fuzzy Naive Bayes (GAFNB) filter
      to classify the protein complexes from candidate subgraphs. It takes
      unreliability into consideration and tackles the presence of unreliable
      interactions in protein complex. We first got candidate protein complexes through
      existed popular methods. Each candidate protein complex is represented by 29
      graph features and 266 biological property based features. GAFNB model is then
      applied to classify the candidate complexes into positive or negative. RESULTS:
      Our evaluation indicates that the protein complex identification algorithms using
      the GAFNB model filtering outperform original ones. For evaluation of GAFNB
      model, we also compared the performance of GAFNB with Naive Bayes (NB). Results
      show that GAFNB performed better than NB. It indicates that a fuzzy model is more
      suitable when unreliability is present. CONCLUSIONS: We conclude that filtering
      candidate protein complexes with GAFNB model can improve the effectiveness of
      protein complex identification. It is necessary to consider the unreliability in
      this task.

PMID- 24565337
TI  - Inferring drug-disease associations from integration of chemical, genomic and
      phenotype data using network propagation.
AB  - BACKGROUND: During the last few years, the knowledge of drug, disease phenotype
      and protein has been rapidly accumulated and more and more scientists have been
      drawn the attention to inferring drug-disease associations by computational
      method. Development of an integrated approach for systematic discovering drug
      disease associations by those informational data is an important issue. METHODS:
      We combine three different networks of drug, genomic and disease phenotype and
      assign the weights to the edges from available experimental data and knowledge.
      Given a specific disease, we use our network propagation approach to infer the
      drug-disease associations. RESULTS: We apply prostate cancer and colorectal
      cancer as our test data. We use the manually curated drug-disease associations
      from comparative toxicogenomics database to be our benchmark. The ranked results
      show that our proposed method obtains higher specificity and sensitivity and
      clearly outperforms previous methods. Our result also show that our method with
      off-targets information gets higher performance than that with only primary drug
      targets in both test data. CONCLUSIONS: We clearly demonstrate the feasibility
      and benefits of using network-based analyses of chemical, genomic and phenotype
      data to reveal drug-disease associations. The potential associations inferred by
      our method provide new perspectives for toxicogenomics and drug reposition
      evaluation.

PMID- 24565340
TI  - Comparison of laryngeal mask airway supreme and laryngeal mask airway proseal for
      laryngopharyngeal trauma and postoperative morbidity in children.
AB  - BACKGROUND AND OBJECTIVES: Laryngeal mask airway (LMA), which has been used
      frequently in airway management, can cause laryngopharyngeal injury and
      morbidity. In this trial, we compare the macroscopic changes on laryngopharyngeal
      structures and the postoperative laryngopharyngeal morbidity by using LMA supreme
      with LMA proseal in children. METHODS: We divided patients into two groups. We
      inserted size three LMA proseal into the first group and size three LMA supreme
      into the second group. Before LMA insertion and after LMA removal, we performed
      direct laryngoscopy on the patients. We compared hyperemia, mucosal injury and
      blood staining on LMA removal, as well as insertion time, rate of success in
      gastric tube insertion on the first attempt, nausea, vomiting, and sore throat
      between the two groups. RESULTS: We recorded no significant differences between
      the two groups for mean operation time, sex, age, weight, rate of success in
      gastric tube insertion on first attempt, nausea, vomiting, sore throat and
      mucosal injury. Mean insertion time for the LMA proseal group was significantly
      longer than the LMA supreme group (p = 0.0001). The ratio of blood staining on
      LMA removal was significantly higher in the LMA proseal group than the LMA
      supreme group (p = 0.034). The patients with blood staining on LMA removal
      exhibited significantly more mucosal hyperemia and injury than the patients with
      clear LMA (p = 0.0001, p = 0.020). CONCLUSION: LMA supreme insertion is faster
      and easier than LMA proseal and causes less laryngopharyngeal injury than LMA
      proseal in children.

PMID- 24565339
TI  - Autoantibodies against MHC class I polypeptide-related sequence A are associated
      with increased risk of concomitant autoimmune diseases in celiac patients.
AB  - BACKGROUND: Overexpression of autologous proteins can lead to the formation of
      autoantibodies and autoimmune diseases. MHC class I polypeptide-related sequence
      A (MICA) is highly expressed in the enterocytes of patients with celiac disease,
      which arises in response to gluten. The aim of this study was to investigate anti
      MICA antibody formation in patients with celiac disease and its association with
      other autoimmune processes. METHODS: We tested serum samples from 383 patients
      with celiac disease, obtained before they took up a gluten-free diet, 428
      patients with diverse autoimmune diseases, and 200 controls for anti-MICA
      antibodies. All samples were also tested for anti-endomysium and anti
      transglutaminase antibodies. RESULTS: Antibodies against MICA were detected in
      samples from 41.7% of patients with celiac disease but in only 3.5% of those from
      controls (P <0.0001) and 8.2% from patients with autoimmune disease (P <0.0001).
      These antibodies disappeared after the instauration of a gluten-free diet. Anti
      MICA antibodies were significantly prevalent in younger patients (P <0.01). Fifty
      eight patients with celiac disease (15.1%) presented a concomitant autoimmune
      disease. Anti-MICA-positive patients had a higher risk of autoimmune disease than
      MICA antibody-negative patients (P <0.0001; odds ratio = 6.11). The risk was even
      higher when we also controlled for age (odds ratio = 11.69). Finally, we found
      that the associated risk of developing additional autoimmune diseases was 16 and
      10 times as high in pediatric patients and adults with anti-MICA, respectively,
      as in those without. CONCLUSIONS: The development of anti-MICA antibodies could
      be related to a gluten-containing diet, and seems to be involved in the
      development of autoimmune diseases in patients with celiac disease, especially
      younger ones.

PMID- 24565341
TI  - Delirium assessment in postoperative patients: Validation of the Portuguese
      version of the Nursing Delirium Screening Scale in critical care.
AB  - BACKGROUND AND OBJECTIVES: The aim of this study was to validate the Portuguese
      version of the Nursing Delirium Screening Scale (Nu-DESC) for use in critical
      care settings. METHODS: We simultaneously and independently evaluated all
      postoperative patients admitted to a surgical Intensive Care Unit (SICU) over a 1
      month period for delirium, using the Portuguese versions of both the Nu-DESC and
      the Intensive Care Delirium Screening Checklist (ICDSC) within 24 hours of
      admission by both the research staff physician and one bedside nurse. We
      determined the diagnostic accuracy of the Nu-DESC using sensitivity, specificity
      and ROC curve analyses. We assessed reliability between nurses and the research
      staff physician for Nu-DESC by intraclass correlation coefficient (ICC). We
      assessed agreement and reliability between Nu-DESC and ICDSC by overall and
      specific proportions of agreement and by kappa statistics. RESULTS: Based on the
      ICDSC, we diagnosed delirium in 12 of the 78 patients. Reliability between nurses
      and the staff physician for total Nu-DESC score was high. Agreement between
      nurses and staff physician in the delirium diagnosis was perfect. The proportion
      of overall agreement between Nu-DESC and ICDSC in the delirium diagnosis was 0.88
      and the kappa ranged from 0.79 to 0.93. Nu-DESC Sensitivity was 100 and
      specificity was 86%. CONCLUSIONS: The Portuguese version of the Nu-DESC appears
      to be an accurate and reliable assessment and monitoring instrument for delirium
      in critical care settings.

PMID- 24565342
TI  - Prospective, randomized clinical trial of laryngeal mask airway Supreme((r)) used
      in patients undergoing general anesthesia.
AB  - BACKGROUND AND OBJECTIVES: Supraglottic airway devices are increasingly used as
      an option to tracheal intubation for elective procedures of varying complexity.
      The aim of this study was to prospectively evaluate the clinical use of the
      laryngeal mask airway Supreme((r)) (LMAS) in patients undergoing elective breast
      surgery and compare it with endotracheal tube (ETT). METHODS: Sixty patients
      undergoing breast procedures under general anesthesia were randomly divided into
      two groups according to the device used (LMAS or ETT). Time of insertion, number
      of insertion attempts, hemodynamic response to insertion, presence of blood on
      the device used; and incidence of sore throat, dysphagia, nausea and vomiting
      were assessed postoperatively. RESULTS: There was no difference between groups
      regarding time of insertion, number of attempts for successful insertion, and
      presence of blood on the device. Heart rate and blood pressure after insertion
      were higher in ETT group. Incidence of sore throat and dysphagia was also higher
      in ETT group after two hours in the postoperative period. There was no difference
      regarding incidence and severity of complications evaluated after six hours
      postoperatively. CONCLUSIONS: The use of the LMAS technique to access airway
      during general anesthesia for elective breast surgery is as safe and effective as
      tracheal intubation, with the advantage of promoting smaller hemodynamic response
      during its management and lower incidence of sore throat and dysphagia in the
      first hours after surgery.

PMID- 24565343
TI  - The antimicrobial effects of ketamine combined with propofol: An in vitro study.
AB  - BACKGROUND AND OBJECTIVES: Ketamine and propofol are the general anesthetics that
      also have antimicrobial and microbial growth-promoting effects, respectively.
      Although these agents are frequently applied together during clinical use, there
      is no data about their total effect on microbial growth when combined. In this
      study, we investigated some organisms' growth in a ketamine and propofol mixture.
      METHOD: We used standard strains including Escherichia coli, Staphylococcus
      aureus, Pseudomonas aeruginosa, and Candida albicans in this study. Time-growth
      analysis was performed to assess microbial growth rates in 1% propofol.
      Antimicrobial activity of ketamine, alone and in propofol was studied with
      microdilution method. RESULTS: In propofol, studied strains grew from 10(3)-10(4)
      cfu/mL to >=10(5) cfu/mL concentrations within 8-16 hours depending on the type
      of organism. Minimal inhibitory concentration (MIC) and minimal bactericidal
      concentration (MBC) (for candida, minimal fungicidal concentration) of ketamine
      were determined as follows (MIC, MBC): E.coli 312.5, 312.5 MUg/mL; S.aureus 19.5,
      156 MUg/mL; P.aeruginosa 312.5, 625 MUg/mL; and C.albicans 156, 156 MUg/ml. In
      ketamine+propofol mixture, ketamine exhibited antimicrobial activity to E.coli,
      P.aeruginosa and C.albicans as MBCs at 1250, 625 and 625 MUg/mL, respectively.
      Growth of S. aureus was not inhibited in this mixture (ketamine
      concentration=1250 MUg/mL). CONCLUSION: Ketamine has sustained its antimicrobial
      activity in a dose-dependent manner against some organisms in propofol, which is
      a strong microbial growth-promoting solution. Combined use of ketamine and
      propofol in routine clinical application may reduce the risk of infection caused
      by accidental contamination. However, one must keep in mind that ketamine cannot
      reduce all pathogenic threats in propofol mixture.

PMID- 24565344
TI  - The growth of bacteria in infusion drugs: propofol 2% supports growth when
      remifentanil and pantoprazole do not.
AB  - BACKGROUND AND OBJECTIVES: Contamination risks of propofol 2%, remifentanil, and
      pantoprazole; and in vitro effects of these drugs on the growth of common
      infective agents in intensive care units were evaluated. METHODS: For detection
      of contamination risk, drugs were prepared ready to use under intensive care unit
      conditions, were tested. Effects of these three drugs on bacterial growth were
      also investigated. Drugs were prepared at the concentrations used in the
      intensive care unit and inoculated with common pathogens after which they were
      incubated at 4 degrees C, 22 degrees C and 36 degrees C. Subcultures were made at
      0, 2, 4 and 8h and colony counts were evaluated. Minimum inhibitory concentration
      values were determined for all drugs at 4 degrees C, 22 degrees C and 36 degrees
      C. RESULTS: No growth was observed in the drugs prepared in the intensive care
      unit. Propofol tended to support while remifentanil inhibited bacterial growth.
      Effect of pantoprozole differed according to the bacteria tested. None of the
      drugs showed antibacterial activity at the maximum concentrations which may be
      achieved in blood of the patients. CONCLUSION: Propofol strongly supports the
      growth of the microorganisms tested, although remifentanil and pantoprazole do
      not. Therefore, it is important to follow the strict aseptic techniques for the
      preparation of propofol.

PMID- 24565345
TI  - Impact of preanesthetic information on anxiety of parents and children.
AB  - BACKGROUND AND OBJECTIVES: Preoperative Anxiety is a negative factor in
      anesthetic and surgical experience. Among the strategies for reducing children's
      anxiety, non-pharmacological strategies are as important as the pharmacological
      ones, but its validity is still controversial. OBJECTIVES: The aim of this study
      was to verify if the information provided to guardians interferes with child
      anxiety. METHODS: 72 children, 4-8 years old, ASA I and II, undergoing elective
      surgical procedures and their guardians were randomly divided into two groups:
      control group (CG) = guardian received conventional information about anesthesia;
      informative group (IG) = guardian received an information leaflet about
      anesthesia. Children's anxiety was assessed using the modified Yale Preoperative
      Anxiety Scale (m-YPAS) on two occasions: at the surgical theater waiting room
      (WR) and at the operating room (OR). Parents' anxiety was assessed using the
      Hamilton Anxiety Scale (HAM-A) at the CT. RESULTS: There was no difference in
      demographic data between groups. The level of anxiety in children showed no
      difference between groups at two measured times. There was statistically
      significant difference in anxiety levels between WR and OR in both groups, p =
      0.0019 for CG and p < 0.0001 for GI, as well as the prevalence of anxiety for CG
      (38.9% WR and 69.4% OR, p = 0.0174) and GI (19.4% WR and 83.3% OR, p < 0.0001).
      The anxiety level of guardians did not differ between groups. CONCLUSION:
      Regardless of the quality of information provided to the guardians, the level and
      prevalence of anxiety in children were low at WR time and significantly increased
      at OR time.

PMID- 24565346
TI  - Femoral nerve block: Assessment of postoperative analgesia in arthroscopic
      anterior cruciate ligament reconstruction.
AB  - BACKGROUND AND OBJECTIVES: Knee anterior cruciate ligament reconstruction (ACLR)
      may be painful in the postoperative period. The primary objective of this study
      was to evaluate whether the use of femoral nerve block (FNB) associated with
      spinal anesthesia would improve the postoperative pain treatment in ACLR and the
      secondary objectives were to evaluate tramadol request and adverse events.
      METHOD: 53 patients were randomly divided into two groups: GA (n =26) received
      spinal anesthesia and GB (n = 27) received spinal anesthesia and FNB. All
      patients received multimodal analgesia and rescue analgesics could be requested
      anytime. Assessments were performed at 6, 12 and 24 hours. RESULTS: There was no
      difference between both groups regarding demographic and clinical- surgical
      variables. There was no difference between groups regarding pain intensity. Mean
      pain scores were higher at 12 hours in GA and there was no change in GB; 55.6% of
      patients reported moderate pain in GA and 53.8% mild pain in GB. There was no
      difference regarding tramadol request. There were no serious adverse events:
      80.8% of patients in GB had motor block of the thigh and two fell. CONCLUSIONS:
      Analgesia was more effective with the combination of spinal and FNB, which
      allowed better control of postoperative pain, assessed 12 hours after anesthesia.
      There was no difference in tramadol request. Patients in this study had no
      serious adverse events; however, one must be attentive to motor paralysis and the
      possibility of falling when FNB is performed.

PMID- 24565347
TI  - Comparative study between doses of intrathecal morphine for analgesia after
      caesarean.
AB  - BACKGROUND AND OBJECTIVES: Analgesia after caesarean section is important because
      postpartum women with pain have difficulty in mobility, which undermines
      breastfeeding. Intrathecal morphine provides adequate and prolonged analgesia
      after cesarean. The aim of this study was to compare the quality of analgesia
      provided by two doses of intrathecal morphine and its side effects in patients
      undergoing cesarean section. METHOD: The study included 123 pregnant women with
      gestational age over 38 weeks and scheduled for cesarean section. The women were
      randomly allocated into two groups to receive either 50 or 100 MUg of intrathecal
      morphine (Group 50/Group 100). All patients were intrathecally anesthetized with
      12 mg of 0.5% hyperbaric bupivacaine. Patients were assessed between the 9(th)
      and 11(th) hour and the 22(nd) and 24(th) hour after blockade for quality of
      analgesia, analgesic consumption, side effects, and main cause of discomfort in
      the first 24 hours after surgery. RESULTS: There was similarity between groups
      regarding anthropometric data and obstetric history. There was no statistical
      difference in pain intensity between groups. In both groups, pain was more
      intense in the first 12 hours after anesthesia (p < 0.001). Tramadol
      hydrochloride consumption and time to first dose were similar in both groups.
      Pruritus was the most common side effect, with statistically higher incidence in
      Group 100 (p = 0.026). CONCLUSIONS: Intrathecal morphine 50 MUg provides the same
      quality of analgesia as 100 MUg, with a lower incidence of side effects.

PMID- 24565348
TI  - Anesthesia for awake craniotomy: case report.
AB  - BACKGROUND AND OBJECTIVES: Some intracranial procedures are achievable with
      patients awake, however, there are challenges ranging from patient compliance to
      homeostasis. The aim of this study is to present a case of intracranial surgery
      for removal of a tumor in the left parietal lobe with the patient awake during
      the procedure. CASE REPORT: After patient selection and psychological
      preparation, the proposed excision of the left parietal lobe lesion in the waking
      state was clarified and accepted. Continuous infusion of propofol and
      remifentanil was administered to maintain a Ramsay score of 2-3. The bilateral
      scalp blockade was performed with ropivacaine. The Mayfield head fixation device
      was installed and drapes adjusted to maintain the airway and eyes accessible for
      mapping with electrical stimulation and tumor excision. For dura mater incision,
      a pad with 2% lidocaine was applied for 3 minutes. The surgery was uneventful.
      The patient was discharged on the seventh day of hospitalization without
      presenting complication. CONCLUSION: Although the maintenance of analgesia and
      hemodynamic stability was a challenge with the patient awake, the target
      controlled infusion of propofol provided the desired level of consciousness,
      remifentanil titrated analgesia and sedation without drug accumulation, and the
      blockade with ropivacaine provided satisfactory analgesia. We conclude that the
      anesthetic technique was satisfactory for our patient.

PMID- 24565349
TI  - Anesthetic approach for a clinical case of intravenous leiomyomatosis: Case
      report.
AB  - BACKGROUND AND OBJECTIVES: The aim of this study was to describe the anesthetic
      approach in a case of intravenous leiomyomatosis with invasion of the inferior
      vena cava and extension to the right atrium, successfully treated with surgical
      approach. CASE REPORT: Female patient, 45 years old, apparently stable until two
      weeks before the admission to the emergency department with complaints of fatigue
      and dyspnea. Echocardiogram was performed, which detected an intracardiac mass.
      Therefore, elective tumorectomy was performed in the vena cava-right atrium and
      right ventricle transition. Histological examination of the specimen suggested
      uterine leiomyoma. Subsequently, to assess the extent, computed tomography was
      done and showed extension to the inferior vena cava and left ovary. Hysterectomy,
      left adnexectomy and right salpingectomy, removal of intravenous leiomyoma, and
      permanent filter placement in the inferior vena cava were proposed. In this
      article, we describe the anesthetic approach with particular emphasis on the
      correction of fluid requirements, as well as postoperative evolution, and we
      highlight possible contributions to future approach of similar cases.
      CONCLUSIONS: Preoperative diagnosis of intravenous leiomyomatosis is extremely
      difficult. Treatment consists of surgical removal. This procedure involves major
      blood loss and, therefore, preoperative preparation was conditioned:
      intraoperative fluid therapy was central and invasive monitoring considered
      predominant to assist in fluid and electrolyte balance of the patient; the
      existence of a clinical laboratory accessible and with rapid response and blood
      gas assessment was crucial; the intensive care unit equipped with ventilator for
      postoperative care proved to be another requirement resulting from this case.

PMID- 24565350
TI  - Life-threatening airway obstruction due to upper airway edema and marked neck
      swelling after labor and delivery.
AB  - BACKGROUND AND OBJECTIVES: Airway changes generally occur in normal gravidas;
      however, these changes could cause critical situations in specific populations.
      OBJECTIVES: This article presents the case of a difficult airway patient that
      went into shock because of atonic bleeding after vaginal delivery for stillbirth.
      CASE REPORT: A 32-yr-old woman with atonic bleeding after vaginal delivery for
      stillbirth was transferred to our hospital. She manifested shock, and her
      respiratory condition was progressively deteriorating. Airway obstruction caused
      by neck swelling and pharyngolaryngeal edema was apparent. We tried tracheal
      intubation using direct and indirect laryngoscopes. However, it turned out that
      insertion of the laryngoscopic devices to the oral cavity was impossible. After
      several attempts using the TrachlightTM, successful intubation was finally made.
      After hysterectomy, she was admitted to the intensive care unit (ICU) and treated
      for five days. At discharge from the ICU, her Mallampati score was I-II. Her body
      weight decreased 60 kg to 51 kg during ICU stay. CONCLUSIONS: We believe that
      concomitant attacks of labor and delivery and fluid resuscitation probably
      worsened upper airway and neck edema enough to cause acute airway obstruction and
      difficult laryngoscopy.

PMID- 24565351
TI  - Case of anaphylaxis induced by rocuronium treated with sugammadex.

PMID- 24565352
TI  - Here/In this issue and there/abstract thinking: personalized psychiatry: are we
      almost there?

PMID- 24565353
TI  - National trends in juvenile competency to stand trial.

PMID- 24565354
TI  - Treating anxiety in youth: does maintenance treatment maintain?

PMID- 24565355
TI  - Emotion, sex, and the medial temporal lobe.

PMID- 24565356
TI  - Inflammation in children and adolescents with neuropsychiatric disorders: a
      systematic review.
AB  - OBJECTIVE: There has been rapid growth in research regarding inflammation in
      neuropsychiatric disorders as it relates to youth. We therefore set out to
      systematically review the literature on inflammation and neuropsychiatric
      disorders in children and adolescents. METHOD: A systematic review of the
      literature was performed according to the Preferred Reporting Items for
      Systematic Reviews and Meta-Analyses (PRISMA) statement. Studies were included if
      proinflammatory markers (PIMs) in children and/or adolescents with
      neuropsychiatric disorders were measured. RESULTS: Sixty-seven studies were
      included, involving 3,952 youth. Evidence for a proinflammatory state is
      strongest for autism spectrum disorders (ASD). PIMs are elevated in children and
      adolescents with major depressive disorder (MDD), bipolar disorder (BD), post
      traumatic stress disorder (PTSD), obsessive-compulsive disorder (OCD), Tourette's
      disorder (TD), attention-deficit/hyperactivity disorder (ADHD), and schizophrenia
      (SZ). However, the data are inconsistent. Evidence for specific PIMs is equivocal
      at this stage, although the findings in youth with MDD, BD, and PTSD converge
      with the extant adult literature in these areas. Definitive conclusions are
      limited by methodologic factors including cross-sectional and retrospective study
      design, between-study differences in specific markers and methods of analysis,
      small sample size, and other sources of heterogeneity. CONCLUSION: The literature
      regarding inflammation among children and adolescents with neuropsychiatric
      disorders represents nearly 4,000 youth. There is preliminary evidence for
      elevated markers of inflammation in this population. Larger, prospective studies
      are needed to realize the goal of inflammatory markers informing clinical
      practice. In the interim, present findings suggest that further examination of
      this topic is warranted.

PMID- 24565357
TI  - 24- and 36-week outcomes for the Child/Adolescent Anxiety Multimodal Study
      (CAMS).
AB  - OBJECTIVE: We report active treatment group differences on response and remission
      rates and changes in anxiety severity at weeks 24 and 36 for the Child/Adolescent
      Anxiety Multimodal Study (CAMS). METHOD: CAMS youth (N = 488; 74% <= 12 years of
      age) with DSM-IV separation, generalized, or social anxiety disorder were
      randomized to 12 weeks of cognitive-behavioral therapy (CBT), sertraline (SRT),
      CBT+SRT (COMB), or medication management/pill placebo (PBO). Responders attended
      6 monthly booster sessions in their assigned treatment arm; youth in COMB and SRT
      continued on their medication throughout this period. Efficacy of COMB, SRT, and
      CBT (n = 412) was assessed at 24 and 36 weeks postrandomization. Youth randomized
      to PBO (n = 76) were offered active CAMS treatment if nonresponsive at week 12 or
      over follow-up and were not included here. Independent evaluators blind to study
      condition assessed anxiety severity, functioning, and treatment response.
      Concomitant treatments were allowed but monitored over follow-up. RESULTS: The
      majority (>80%) of acute responders maintained positive response at both weeks 24
      and 36. Consistent with acute outcomes, COMB maintained advantage over CBT and
      SRT, which did not differ, on dimensional outcomes; the 3 treatments did not
      differ on most categorical outcomes over follow-up. Compared to COMB and CBT,
      youth in SRT obtained more concomitant psychosocial treatments, whereas those in
      SRT and CBT obtained more concomitant combined (medication plus psychosocial)
      treatment. CONCLUSIONS: COMB maintained advantage over CBT and SRT on some
      measures over follow-up, whereas the 2 monotherapies remained indistinguishable.
      The observed convergence of COMB and monotherapy may be related to greater use of
      concomitant treatment during follow-up among youth receiving the monotherapies,
      although other explanations are possible. Although outcomes were variable, most
      CAMS-treated youth experienced sustained treatment benefit. Clinical trial
      registration information-Child and Adolescent Anxiety Disorders (CAMS); URL:
      http://clinicaltrials.gov. Unique identifier: NCT00052078.

PMID- 24565359
TI  - Preschool environment and temperament as predictors of social and nonsocial
      anxiety disorders in middle adolescence.
AB  - OBJECTIVE: Of the few risk factors identified for the development of anxiety
      disorders, behavioral inhibition has received the strongest support. However,
      studies examining prediction of anxiety disorder from inhibition over time have
      not been extensive, and very few have assessed the impact of inhibition assessed
      early in life on anxiety in adolescence. METHOD: The current study assessed 3
      risk factors among 91 children when they were approximately 4 years of age, and
      determined anxiety diagnoses when the children were in midadolescence (mean age,
      15 years). Children were included in the study at preschool age if they scored
      high (n = 57) or low (n = 34) on behavioral inhibition. Maternal anxiousness and
      maternal attitudes toward the child were assessed at the same time. Diagnoses at
      age 15 years were categorized as social anxiety disorder or other anxiety
      disorders. RESULTS: Social anxiety disorder at age 15 years was predicted by both
      inhibition and maternal anxiousness at age 4 years, whereas other anxiety
      disorders were predicted only by maternal anxiousness. Almost 37% of inhibited
      preschool-aged children demonstrated social anxiety disorder at age 15, compared
      with 15% of uninhibited children. CONCLUSIONS: The results support a growing body
      of research pointing to the importance of behavioral inhibition as a risk for
      social anxiety well into adolescence, and also highlight maternal anxiousness as
      a more general risk across anxiety disorders.

PMID- 24565358
TI  - A follow-up study of maternal expressed emotion toward children with Attention
      Deficit/Hyperactivity Disorder (ADHD): relation with severity and persistence of
      ADHD and comorbidity.
AB  - OBJECTIVE: Attention-deficit/hyperactivity disorder (ADHD) is associated with
      conflicted parent-child relationships. The underlying mechanisms of this
      association are not yet fully understood. We investigated the cross-sectional and
      longitudinal relationships between externalizing psychopathology in children with
      ADHD, and expressed emotion (EE; warmth and criticism) and psychopathology in
      mothers. METHOD: In this 6-year follow-up study, 385 children with an ADHD
      combined subtype were included at baseline (mean, 11.5 years, 83.4% male), of
      which 285 children (74%) were available at follow-up (mean, 17.5 years, 83.5%
      male). At both time points, measures of child psychopathology (i.e., ADHD
      severity, oppositional, and conduct problems), maternal EE, and maternal
      psychopathology (i.e., ADHD and affective problems) were obtained. RESULTS: EE
      was not significantly correlated over time. At baseline, we found a nominally
      negative association (p <= .05) between maternal warmth and child ADHD severity.
      At follow-up, maternal criticism was significantly associated with child
      oppositional problems, and nominally with child conduct problems. Maternal warmth
      was nominally associated with child oppositional and conduct problems. These
      associations were independent of maternal psychopathology. No longitudinal
      associations were found between EE at baseline and child psychopathology at
      follow-up, or child psychopathology at baseline and EE at follow-up. CONCLUSIONS:
      The results support previous findings of cross-sectional associations between
      parental EE and child psychopathology. This, together with the finding that EE
      was not stable over 6 years, suggests that EE is a momentary state measure
      varying with contextual and developmental factors. EE does not appear to be a
      risk factor for later externalizing behavior in children with ADHD.

PMID- 24565360
TI  - Behavioral and cognitive characteristics of females and males with autism in the
      Simons Simplex Collection.
AB  - OBJECTIVE: To examine differences in behavioral symptoms and cognitive
      functioning between males and females with autism spectrum disorder (ASD).
      METHOD: We analyzed data from 2,418 probands with autism (304 females and 2,114
      males) included in the Simons Simplex Collection. Sex differences were evaluated
      across measures of autism symptoms, cognitive and motor functioning, adaptive
      behavior, and associated behavior problems. Measurement bias was examined using
      latent variable models of symptoms. Unadjusted and propensity-adjusted analyses
      were computed to ensure that sex differences were not due to unbalanced sampling.
      Moderator and mediator analyses evaluated whether sex differences were modified
      by clinical characteristics or were driven by cognitive ability. RESULTS: Females
      with ASD had greater social communication impairment, lower levels of restricted
      interests, lower cognitive ability, weaker adaptive skills, and greater
      externalizing problems relative to males. Symptom differences could not be
      accounted for by measurement differences, indicating that diagnostic instruments
      captured autism similarly in males and females. IQ reductions mediated greater
      social impairment and reduced adaptive behavior in females with ASD, but did not
      mediate reductions in restricted interests or increases in irritability.
      CONCLUSIONS: A specific female ASD phenotype is emerging that cannot be accounted
      for by differential symptom measurement. The present data suggest that the
      relatively low proportion of high-functioning females may reflect the effect of
      protective biological factors or may be due to under-identification. Additional
      carefully accrued samples are needed to confirm the present pattern and to
      evaluate whether observed sex ratios in high-functioning cases are reduced if
      female-specific indicators of restricted interests are included.

PMID- 24565361
TI  - Sex differences in the effect of puberty on hippocampal morphology.
AB  - OBJECTIVE: Puberty is the defining process of adolescence, and is accompanied by
      divergent trajectories of behavior and cognition for males and females. Here we
      examine whether sex differences exist in the effect of puberty on the morphology
      of the hippocampus and amygdala. METHOD: T1-weighted structural neuroimaging was
      performed in a sample of 524 pre- or postpubertal individuals ages 10 to 22
      years. Hippocampal and amygdala volume and shape were quantified using the
      Functional Magnetic Resonance Imaging of the Brain (FMRIB) Software Library (FSL)
      FIRST procedure and scaled by intracranial volume. The effects on regional volume
      of age, sex, puberty, and their interactions were examined using linear
      regression. Postpubertal sex differences were examined using a vertex analysis.
      RESULTS: Prepubertal males and females had similar hippocampal volumes, whereas
      postpubertal females had significantly larger bilateral hippocampi, resulting in
      a significant puberty-by-sex interaction even when controlling for age and age-by
      sex. This effect was regionally specific and was not apparent in the amygdala.
      Vertex analysis revealed that postpubertal differences were most prominent in the
      lateral aspect of the hippocampus bilaterally, corresponding to the CA1 subfield.
      CONCLUSIONS: These results establish that there are regionally specific sex
      differences in the effect of puberty on the hippocampus. These findings are
      relevant for the understanding of psychiatric disorders that have both
      hippocampal dysfunction and prominent gender disparities during adolescence.

PMID- 24565365
TI  - Small bowel obstruction in the virgin abdomen: the need for a mandatory
      laparotomy explored.
AB  - BACKGROUND: A laparotomy is still considered mandatory for patients without
      previous abdominal surgery presenting with a small bowel obstruction (SBO)
      because of a perceived high incidence of underlying lesions. However, there is no
      evidence in literature to support this assumption. We analyzed the etiology of
      SBO in this subgroup of patients to establish the need for a mandatory
      laparotomy. METHODS: A retrospective analysis was conducted over a 5-year period.
      Basic demographics, radiology results, operative findings, and outpatient
      investigations were analyzed. RESULTS: Of 689 patients presenting with an SBO, a
      total of 62 patients, 9.0%, had a virgin abdomen. A known underlying disease
      (inflammatory bowel disease, malignancy) was the cause in 13 patients. The
      remaining 49 patients had adhesions in 75.5% and a newly diagnosed malignancy in
      10.2% as a cause. CONCLUSIONS: Adhesions are by far the most likely cause of SBO
      in patients without previous abdominal surgery followed by a small number of
      newly diagnosed malignancies. Both prevalences are in equal proportion to
      patients with previous abdominal surgery. A trial of nonoperative management may
      therefore be justified.

PMID- 24565362
TI  - Abnormal amygdala functional connectivity associated with emotional lability in
      children with attention-deficit/hyperactivity disorder.
AB  - OBJECTIVE: A substantial proportion of children with attention
      deficit/hyperactivity disorder (ADHD) also display emotion regulation deficits
      manifesting as chronic irritability, severe temper outbursts, and aggression. The
      amygdala is implicated in emotion regulation, but its connectivity and relation
      to emotion regulation in ADHD has yet to be explored. The purpose of this study
      was to examine the relationship between intrinsic functional connectivity (iFC)
      of amygdala circuits and emotion regulation deficits in youth with ADHD. METHOD:
      Bilateral amygdala iFC was examined using functional magnetic resonance imaging
      in 63 children with ADHD, aged 6 to 13 years. First, we examined the relationship
      between amygdala IFC and parent ratings of emotional lability (EL) in children
      with ADHD. Second, we compared amygdala iFC across subgroups of children with
      ADHD and high EL (n = 18), ADHD and low EL (n = 20), and typically developing
      children (TDC), all with low EL (n = 19). RESULTS: Higher EL ratings were
      associated with greater positive iFC between the amygdala and rostral anterior
      cingulate cortex in youth with ADHD. EL scores were also negatively associated
      with iFC between bilateral amygdala and posterior insula/superior temporal gyrus.
      Patterns of amygdala-cortical iFC in ADHD participants with low EL were not
      different from the comparison group, and the effect sizes for these comparisons
      were smaller than those for the trend-level differences observed between the high
      EL and TDC groups. CONCLUSIONS: In children with ADHD and a range of EL, deficits
      in emotion regulation were associated with altered amygdala-cortical iFC. When
      comparing groups that differed on ADHD status but not EL, differences in amygdala
      iFC were small and nonsignificant, highlighting the specificity of this finding
      to emotional deficits, independent of other ADHD symptoms.

PMID- 24565363
TI  - White matter abnormalities and cognitive impairment in early-onset schizophrenia
      spectrum disorders.
AB  - OBJECTIVE: To characterize white matter abnormalities in adolescents with early
      onset schizophrenia (EOS) relative to 3 comparison groups (adolescents at
      clinical high risk for developing schizophrenia [CHR], adolescents with cannabis
      use disorder [CUD], and healthy controls [HC]), and to identify neurocognitive
      correlates of white matter abnormalities in EOS. METHOD: We used diffusion tensor
      imaging and tractography methods to examine fractional anisotropy (FA) of the
      cingulum bundle, superior longitudinal fasciculus, corticospinal tract (CST),
      inferior longitudinal fasciculus (ILF), inferior fronto-occipital fasciculus
      (IFOF), and uncinate fasciculus in adolescents with EOS (n = 55), CHR (n = 21),
      CUD (n = 31), and HC (n = 55). FA in tracts that were significantly altered in
      EOS was correlated with neurocognitive performance. RESULTS: EOS and CHR groups
      had significantly lower FA than HC in 4 tracts, namely, bilateral CST, left ILF,
      and left IFOF. CUD had lower FA than HC in left IFOF. Lower FA in left IFOF and
      left ILF predicted worse neurocognitive performance in EOS. CONCLUSIONS: This
      study identified white matter abnormalities of the left ILF and left IFOF as
      possible biomarkers of vulnerability for developing schizophrenia. Lower FA in
      these tracts may disrupt functioning of ventral visual and language streams,
      producing domain-specific neurocognitive deficits that interfere with higher
      order cognitive abilities.

PMID- 24565366
TI  - Efficient mining gapped sequential patterns for motifs in biological sequences.
AB  - BACKGROUND: Pattern mining for biological sequences is an important problem in
      bioinformatics and computational biology. Biological data mining yield impact in
      diverse biological fields, such as discovery of co-occurring biosequences, which
      is important for biological data analyses. The approaches of mining sequential
      patterns can discover all-length motifs of biological sequences. Nevertheless,
      traditional approaches of mining sequential patterns inefficiently mine DNA and
      protein data since the data have fewer letters and lengthy sequences.
      Furthermore, gap constraints are important in computational biology since they
      cope with irrelative regions, which are not conserved in evolution of biological
      sequences. RESULTS: We devise an approach to efficiently mine sequential patterns
      (motifs) with gap constraints in biological sequences. The approach is the Depth
      First Spelling algorithm for mining sequential patterns of biological sequences
      with Gap constraints (termed DFSG). CONCLUSIONS: PrefixSpan is one of the most
      efficient methods in traditional approaches of mining sequential patterns, and it
      is the basis of GenPrefixSpan. GenPrefixSpan is an approach built on PrefixSpan
      with gap constraints, and therefore we compare DFSG with GenPrefixSpan. In the
      experimental results, DFSG mines biological sequences much faster than
      GenPrefixSpan.

PMID- 24565368
TI  - Cutaneous leishmaniasis caused by Leishmania killicki, Algeria.

PMID- 24565369
TI  - Alemtuzumab induction therapy in solid organ transplantation.
AB  - Alemtuzumab (Campath) is a monoclonal antibody that has a profound lymphocyte
      depleting effect, targeting the CD52 antigen that is present on all lymphocytes.
      Alemtuzumab has been used for the treatment of chronic lymphocytic leukaemia and
      various autoimmune disorders, and has also shown potential as an induction agent
      in the prevention of rejection following solid organ transplantation. Alemtuzumab
      has been studied in randomised controlled trials and has demonstrated low levels
      of rejection in renal transplant recipients compared with other induction agents,
      albeit mainly in the early months following transplantation. Studies have shown
      that alemtuzumab enables the use of lower calcineurin inhibitor (CNI) maintenance
      drugs; however, this reduction in nephrotoxic immunosuppression has not
      consistently been matched by an improvement in renal function. The hypothesis has
      been suggested that alemtuzumab might allow the development of immunosuppressive
      regimens that avoid CNIs completely; studies have investigated the combination of
      alemtuzumab with mammalian target of rapamycin-inhibitor maintenance therapy,
      and, in particular, sirolimus. Initial studies with this combination showed that
      regimens of sirolimus alone and of sirolimus with mycophenolate mofetil were
      unsuccessful, with a high rate of rejection and complications. Subsequent studies
      have targeted the combination of alemtuzumab induction with a short course of a
      CNI, before switching to maintenance therapy with sirolimus. This regimen might
      combine good protection from acute cellular rejection and chronic nephrotoxicity.
      A randomised controlled trial has been established to study this regimen, with
      results pending. 

PMID- 24565367
TI  - Pharmacological recommendations for the symptomatic treatment of dementia: the
      Canadian Consensus Conference on the Diagnosis and Treatment of Dementia 2012.
AB  - BACKGROUND: While there have been no new medications approved for the treatment
      of Alzheimer's disease (AD) or other dementias in Canada since 2004, the Canadian
      Consensus Conference on the Diagnosis and Treatment of Dementia (CCCDTD) reviewed
      and updated the clinical practice guidelines on the pharmacological management of
      dementia that were published previously. METHODS: This review focused on the
      literature for the pharmacological treatment of dementia based on studies
      published since the third CCCDTD in 2006. A literature search of English-language
      medical databases was preformed for studies pertaining to the pharmacological
      treatment of AD and other dementias that examined the management of cognitive and
      functional impairment, as well as neuropsychiatric symptoms. All previous
      recommendations were reviewed, and only those that required updating based on new
      published studies were revised. Several new recommendations were also added.
      Recommendations were rated for quality of evidence and were approved by
      consensus. RESULTS: There were 15 revised or new recommendations approved by
      consensus. The revised recommendations included acknowledging that cholinesterase
      inhibitors (ChEIs) possess a class effect and any of the agents can be used for
      AD across the spectrum of severity and with co-existing cerebrovascular disease.
      There was insufficient evidence to recommend for or against the use of ChEIs in
      combination with memantine for the primary indication of treating
      neuropsychiatric symptoms, or for the treatment of vascular dementia.
      Recommendations for the discontinuation of cognitive enhancers were revised and
      clarified, as well as the risks associated with discontinuing these drugs. ChEIs
      were recommended as a treatment option for dementia with Parkinson's disease.
      Risks associated with use of antipsychotics for neuropsychiatric symptoms were
      strengthened, and guidelines regarding the use of antidepressants for affective
      disturbances in dementia were weakened, and are now considered an option but not
      a firm recommendation. Valproate was recommended not to be used, and there was
      insufficient evidence to recommend for or against the use of selective serotonin
      reuptake inhibitors or trazodone for the treatment of agitation and aggression.
      CONCLUSION: In spite of the lack of new therapeutic agents for the treatment of
      dementia, recent studies have helped to clarify and strengthen recommendations to
      optimize the pharmacological management of these illnesses.

PMID- 24565370
TI  - Multivariate generalized multifactor dimensionality reduction to detect gene-gene
      interactions.
AB  - BACKGROUND: Recently, one of the greatest challenges in genome-wide association
      studies is to detect gene-gene and/or gene-environment interactions for common
      complex human diseases. Ritchie et al. (2001) proposed multifactor dimensionality
      reduction (MDR) method for interaction analysis. MDR is a combinatorial approach
      to reduce multi-locus genotypes into high-risk and low-risk groups. Although MDR
      has been widely used for case-control studies with binary phenotypes, several
      extensions have been proposed. One of these methods, a generalized MDR (GMDR)
      proposed by Lou et al. (2007), allows adjusting for covariates and applying to
      both dichotomous and continuous phenotypes. GMDR uses the residual score of a
      generalized linear model of phenotypes to assign either high-risk or low-risk
      group, while MDR uses the ratio of cases to controls. METHODS: In this study, we
      propose multivariate GMDR, an extension of GMDR for multivariate phenotypes.
      Jointly analysing correlated multivariate phenotypes may have more power to
      detect susceptible genes and gene-gene interactions. We construct generalized
      estimating equations (GEE) with multivariate phenotypes to extend generalized
      linear models. Using the score vectors from GEE we discriminate high-risk from
      low-risk groups. We applied the multivariate GMDR method to the blood pressure
      data of the 7,546 subjects from the Korean Association Resource study: systolic
      blood pressure (SBP) and diastolic blood pressure (DBP). We compare the results
      of multivariate GMDR for SBP and DBP to the results from separate univariate GMDR
      for SBP and DBP, respectively. We also applied the multivariate GMDR method to
      the repeatedly measured hypertension status from 5,466 subjects and compared its
      result with those of univariate GMDR at each time point. RESULTS: Results from
      the univariate GMDR and multivariate GMDR in two-locus model with both blood
      pressures and hypertension phenotypes indicate best combinations of SNPs whose
      interaction has significant association with risk for high blood pressures or
      hypertension. Although the test balanced accuracy (BA) of multivariate analysis
      was not always greater than that of univariate analysis, the multivariate BAs
      were more stable with smaller standard deviations. CONCLUSIONS: In this study, we
      have developed multivariate GMDR method using GEE approach. It is useful to use
      multivariate GMDR with correlated multiple phenotypes of interests.

PMID- 24565371
TI  - Information visualisation for science and policy: engaging users and avoiding
      bias.
AB  - Visualisations and graphics are fundamental to studying complex subject matter.
      However, beyond acknowledging this value, scientists and science-policy
      programmes rarely consider how visualisations can enable discovery, create
      engaging and robust reporting, or support online resources. Producing accessible
      and unbiased visualisations from complicated, uncertain data requires expertise
      and knowledge from science, policy, computing, and design. However, visualisation
      is rarely found in our scientific training, organisations, or collaborations. As
      new policy programmes develop [e.g., the Intergovernmental Platform on
      Biodiversity and Ecosystem Services (IPBES)], we need information visualisation
      to permeate increasingly both the work of scientists and science policy. The
      alternative is increased potential for missed discoveries, miscommunications,
      and, at worst, creating a bias towards the research that is easiest to display. 

PMID- 24565372
TI  - Pressure ulcer prevention knowledge among Jordanian nurses: a cross- sectional
      study.
AB  - BACKGROUND: Pressure ulcer remains a significant problem in the healthcare
      system. In addition to the suffering it causes patients, it bears a growing
      financial burden. Although pressure ulcer prevention and care have improved in
      recent years, pressure ulcer still exists and occurs in both hospital and
      community settings. In Jordan, there are a handful of studies on pressure ulcer.
      This study aims to explore levels of knowledge and knowledge sources about
      pressure ulcer prevention, as well as barriers to implementing pressure ulcer
      prevention guidelines among Jordanian nurses. METHODS: Using a cross-sectional
      study design and a self-administered questionnaire, data was collected from 194
      baccalaureate and master's level staff nurses working in eight Jordanian
      hospitals. From September to October of 2011, their knowledge levels about
      pressure ulcer prevention and the sources of this knowledge were assessed, along
      with the barriers which reduce successful pressure ulcer care and
      prevention.ANOVA and t-test analysis were used to test the differences in nurses'
      knowledge according to participants' characteristics. Means, standard deviation,
      and frequencies were used to describe nurses' knowledge levels, knowledge
      sources, and barriers to pressure ulcer prevention. RESULTS: The majority (73%, n
      = 141) of nurses had inadequate knowledge about pressure ulcer prevention. The
      mean scores of the test for all participants was 10.84 out of 26 (SD = 2.3, range
      = 5-17), with the lowest score in themes related to PU etiology, preventive
      measures to reduce amount of pressure/shear, and risk assessment. In-service
      training was the second source of education on pressure ulcer, coming after
      university training. Shortage of staff and lack of time were the most frequently
      cited barriers to carrying out pressure ulcer risk assessment, documentation, and
      prevention. CONCLUSIONS: This study highlights concerns about Jordanian nurses'
      knowledge of pressure ulcer prevention. The results of the current study showed
      inadequate knowledge among Jordanian nurses about pressure ulcer prevention based
      on National Pressure Ulcer Advisory Panel guidelines. Also, the low level of
      nurses' pressure ulcer knowledge suggests poor dissemination of pressure ulcer
      knowledge in Jordan, a suggestion supported by the lack of relationship between
      years of experience and pressure ulcer knowledge.

PMID- 24565373
TI  - Emodin enhances osteogenesis and inhibits adipogenesis.
AB  - BACKGROUND: It has been suggested that the formation of osteoblasts in bone
      marrow is closely associated with adipogenesis, and the balance between
      osteogenesis and adipogenesis differentiation of MSCs (mesenchymal stem cells) is
      disrupted in osteoporosis. In order to improve the treatment of osteoporosis,
      available agents with roles of regulating the balance is highly desirable. Emodin
      is a natural anthraquinone derivative extracted from Chinese herbs, which have
      been used to treat bone diseases for thousands of years. However, the underlying
      molecular mechanisms of emodin in modulating osteogenesis and adipogenesis remain
      poorly understood. METHODS: The molecular mechanisms of emodin on the processes
      of osteogenesis and adipogenesis in ovariectomized mouse and BMSCs (bone marrow
      mesenchymal stem cells) have been studied. We have analyzed the effects of emodin
      in vivo and in vitro. Female ICR mice were assigned to three groups: sham group,
      ovariectomy group, emodin group. Efficacy was evaluated by H&E,
      immunohistochemical assay and Micro-CT. In vitro, we analyze the effect of emodin
      -at concentrations between 0.1 MUM and 10 MUM--on the processes of inducing
      osteogenesis and inhibiting adipogenesis in BMSCs by ALP, Oil red O staining,
      real time RT-PCR and western blot. RESULTS: As our experiment shows that emodin
      could increase the number of osteoblast, BMD (bone mineral density), BV/TV
      (trabecular bone volume fraction), Tb.N (trabecular number) and Conn.D
      (connectivity density) of OVX (ovariectomized) mice and decrease the bone marrow
      fat tissue and adipocytes. The genes and proteins expression of osteogenesis
      markers, such as Runx2, osterix, collagen type I, osteocalcin, or ALP were up
      regulated. While, the genes and proteins involved in adipogenesis, PPARgamma,
      C/EBPalpha and ap2 were down-regulated. CONCLUSION: It proves that emodin
      inhibits adipocyte differentiation and enhances osteoblast differentiation from
      BMSCs.

PMID- 24565375
TI  - Recreating the female reproductive tract in vitro using iPSC technology in a
      linked microfluidics environment.
AB  - The female reproductive tract produces hormones for reproductive function and
      cardiovascular, bone and sexual health; the tract supplies a finite number of
      gametes, and it supports fetal development. Diseases that affect each of the
      female reproductive tract organs, along with treatments that have direct,
      deleterious effects on the reproductive tract (for example, chemotherapeutics),
      are understudied due to the lack of model systems that phenocopy in vivo
      function. This review describes a path toward developing female reproductive
      tract mimics. The models use isolated primary support cells cultured onto a
      biological scaffold and within a microfluidic system to create a niche and
      support the desired differentiation of epithelia, germ and somatic cells from
      patient-derived induced pluripotent stem cells. Improving our fund of knowledge
      about reproductive tract biology and creating reproductive organs for patients
      who have lost gonadal, uterine or vaginal/ cervical function is a major step
      forward in women's health and an important advancement in personalized medicine. 

PMID- 24565374
TI  - Structure, assembly and dynamics of macromolecular complexes by single particle
      cryo-electron microscopy.
AB  - BACKGROUND: Proteins in their majority act rarely as single entities.
      Multisubunit macromolecular complexes are the actors in most of the cellular
      processes. These nanomachines are hold together by weak protein-protein
      interactions and undergo functionally important conformational changes. TFIID is
      such a multiprotein complex acting in eukaryotic transcription initiation. This
      complex is first to be recruited to the promoter of the genes and triggers the
      formation of the transcription preinitiation complex involving RNA polymerase II
      which leads to gene transcription. The exact role of TFIID in this process is not
      yet understood. METHODS: Last generation electron microscopes, improved data
      collection and new image analysis tools made it possible to obtain structural
      information of biological molecules at atomic resolution. Cryo-electron
      microscopy of vitrified samples visualizes proteins in a fully hydrated, close to
      native state. Molecular images are recorded at liquid nitrogen temperature in low
      electron dose conditions to reduce radiation damage. Digital image analysis of
      these noisy images aims at improving the signal-to-noise ratio, at separating
      distinct molecular views and at reconstructing a three-dimensional model of the
      biological particle. RESULTS: Using these methods we showed the early events of
      an activated transcription initiation process. We explored the interaction of the
      TFIID coactivator with the yeast Rap1 activator, the transcription factor TFIIA
      and the promoter DNA. We demonstrated that TFIID serves as an assembly platform
      for transient protein-protein interactions, which are essential for transcription
      initiation. CONCLUSIONS: Recent developments in electron microscopy have provided
      new insights into the structural organization and the dynamic reorganization of
      large macromolecular complexes. Examples of near-atomic resolutions exist but the
      molecular flexibility of macromolecular complexes remains the limiting factor in
      most case. Electron microscopy has the potential to provide both structural and
      dynamic information of biological assemblies in order to understand the molecular
      mechanisms of their functions.

PMID- 24565376
TI  - Joint clustering of protein interaction networks through Markov random walk.
AB  - Biological networks obtained by high-throughput profiling or human curation are
      typically noisy. For functional module identification, single network clustering
      algorithms may not yield accurate and robust results. In order to borrow
      information across multiple sources to alleviate such problems due to data
      quality, we propose a new joint network clustering algorithm ASModel in this
      paper. We construct an integrated network to combine network topological
      information based on protein-protein interaction (PPI) datasets and homological
      information introduced by constituent similarity between proteins across
      networks. A novel random walk strategy on the integrated network is developed for
      joint network clustering and an optimization problem is formulated by searching
      for low conductance sets defined on the derived transition matrix of the random
      walk, which fuses both topology and homology information. The optimization
      problem of joint clustering is solved by a derived spectral clustering algorithm.
      Network clustering using several state-of-the-art algorithms has been implemented
      to both PPI networks within the same species (two yeast PPI networks and two
      human PPI networks) and those from different species (a yeast PPI network and a
      human PPI network). Experimental results demonstrate that ASModel outperforms the
      existing single network clustering algorithms as well as another recent joint
      clustering algorithm in terms of complex prediction and Gene Ontology (GO)
      enrichment analysis. 

PMID- 24565377
TI  - Good days and bad days in dementia: a qualitative chart review of variable
      symptom expression.
AB  - BACKGROUND: Despite its importance in the lived experience of dementia, symptom
      fluctuation has been little studied outside Lewy body dementia. We aimed to
      characterize symptom fluctuation in patients with Alzheimer's disease (AD) and
      mixed dementia. METHODS: A qualitative analysis of health records that included
      notations on good days and bad days yielded 52 community-dwelling patients
      (women, n = 30; aged 39-91 years; mild dementia, n = 26, chiefly AD, n = 36).
      RESULTS: Good days/bad days were most often described as changes in the same core
      set of symptoms (e.g. less/more verbal repetition). In other cases, only good or
      only bad days were described (e.g., no bad days, better sense of humor on good
      days). Good days were typically associated with improved global cognition,
      function, interest, and initiation. Bad days were associated with frequent verbal
      repetition, poor memory, increased agitation and other disruptive behaviors.
      CONCLUSIONS: Clinically important variability in symptoms appears common in AD
      and mixed dementia. Even so, what makes a day "good" is not simply more (or less)
      of what makes a day "bad". Further investigation of the factors that facilitate
      or encourage good days and mitigate bad days may help improve quality of life for
      patients and caregivers.

PMID- 24565379
TI  - Postmortem diagnosis of invasive meningococcal disease.
AB  - We diagnosed invasive meningococcal disease by using immunohistochemical staining
      of embalmed tissue and PCR of vitreous humor from 2 men in New York City. Because
      vitreous humor is less subject than other body fluids to putrefaction, it is a
      good material for postmortem analysis. 

PMID- 24565381
TI  - Advancing data reuse in phyloinformatics using an ontology-driven Semantic Web
      approach.
AB  - Phylogenetic analyses can resolve historical relationships among genes, organisms
      or higher taxa. Understanding such relationships can elucidate a wide range of
      biological phenomena, including, for example, the importance of gene and genome
      duplications in the evolution of gene function, the role of adaptation as a
      driver of diversification, or the evolutionary consequences of biogeographic
      shifts. Phyloinformaticists are developing data standards, databases and
      communication protocols (e.g. Application Programming Interfaces, APIs) to extend
      the accessibility of gene trees, species trees, and the metadata necessary to
      interpret these trees, thus enabling researchers across the life sciences to
      reuse phylogenetic knowledge. Specifically, Semantic Web technologies are being
      developed to make phylogenetic knowledge interpretable by web agents, thereby
      enabling intelligently automated, high-throughput reuse of results generated by
      phylogenetic research. This manuscript describes an ontology-driven, semantic
      problem-solving environment for phylogenetic analyses and introduces artefacts
      that can promote phyloinformatic efforts to promote accessibility of trees and
      underlying metadata. PhylOnt is an extensible ontology with concepts describing
      tree types and tree building methodologies including estimation methods, models
      and programs. In addition we present the PhylAnt platform for annotating
      scientific articles and NeXML files with PhylOnt concepts. The novelty of this
      work is the annotation of NeXML files and phylogenetic related documents with
      PhylOnt Ontology. This approach advances data reuse in phyloinformatics. 

PMID- 24565378
TI  - Chronic stress enhances microglia activation and exacerbates death of nigral
      dopaminergic neurons under conditions of inflammation.
AB  - BACKGROUND: Parkinson's disease is an irreversible neurodegenerative disease
      linked to progressive movement disorders and is accompanied by an inflammatory
      reaction that is believed to contribute to its pathogenesis. Since sensitivity to
      inflammation is not the same in all brain structures, the aim of this work was to
      test whether physiological conditions as stress could enhance susceptibility to
      inflammation in the substantia nigra, where death of dopaminergic neurons takes
      place in Parkinson's disease. METHODS: To achieve our aim, we induced an
      inflammatory process in nonstressed and stressed rats (subject to a chronic
      variate stress) by a single intranigral injection of lipopolysaccharide, a potent
      proinflammogen. The effect of this treatment was evaluated on inflammatory
      markers as well as on neuronal and glial populations. RESULTS: Data showed a
      synergistic effect between inflammation and stress, thus resulting in higher
      microglial activation and expression of proinflammatory markers. More important,
      the higher inflammatory response seen in stressed animals was associated with a
      higher rate of death of dopaminergic neurons in the substantia nigra, the most
      characteristic feature seen in Parkinson's disease. This effect was dependent on
      glucocorticoids. CONCLUSIONS: Our data demonstrate that stress sensitises
      midbrain microglia to further inflammatory stimulus. This suggests that stress
      may be an important risk factor in the degenerative processes and symptoms of
      Parkinson's disease.

PMID- 24565382
TI  - M-Finder: Uncovering functionally associated proteins from interactome data
      integrated with GO annotations.
AB  - BACKGROUND: Protein-protein interactions (PPIs) play a key role in understanding
      the mechanisms of cellular processes. The availability of interactome data has
      catalyzed the development of computational approaches to elucidate functional
      behaviors of proteins on a system level. Gene Ontology (GO) and its annotations
      are a significant resource for functional characterization of proteins. Because
      of wide coverage, GO data have often been adopted as a benchmark for protein
      function prediction on the genomic scale. RESULTS: We propose a computational
      approach, called M-Finder, for functional association pattern mining. This method
      employs semantic analytics to integrate the genome-wide PPIs with GO data. We
      also introduce an interactive web application tool that visualizes a functional
      association network linked to a protein specified by a user. The proposed
      approach comprises two major components. First, the PPIs that have been generated
      by high-throughput methods are weighted in terms of their functional consistency
      using GO and its annotations. We assess two advanced semantic similarity metrics
      which quantify the functional association level of each interacting protein pair.
      We demonstrate that these measures outperform the other existing methods by
      evaluating their agreement to other biological features, such as sequence
      similarity, the presence of common Pfam domains, and core PPIs. Second, the
      information flow-based algorithm is employed to discover a set of proteins
      functionally associated with the protein in a query and their links efficiently.
      This algorithm reconstructs a functional association network of the query
      protein. The output network size can be flexibly determined by parameters.
      CONCLUSIONS: M-Finder provides a useful framework to investigate functional
      association patterns with any protein. This software will also allow users to
      perform further systematic analysis of a set of proteins for any specific
      function. It is available online at http://bionet.ecs.baylor.edu/mfinder.

PMID- 24565383
TI  - SBA recommendations for regional anesthesia safety in patients taking
      anticoagulants.

PMID- 24565384
TI  - Premedication with midazolam prior to caesarean section has no neonatal adverse
      effects.
AB  - Like all surgical patients, obstetric patients also feel operative stress and
      anxiety. This can be prevented by giving patients detailed information about
      their operation and with preoperative pharmacological medications. Because of
      depressive effects of sedatives on newborns, pharmacological medications are
      omitted, especially in obstetric patients. The literature contains few studies
      concerning preoperative midazolam use in Caesarian section (C/S) patients. Our
      aim in this study was to help patients undergoing C/S surgery. One group
      scheduled for elective C/S received midazolam 0.025 mg kg(-1) intravenously, the
      other received saline. Maternal anxiety was evaluated using Amsterdam
      Preoperative Anxiety and Information Scale (APAIS) scores, and newborns were
      evaluated using Apgar and the Neonatal Neurologic and Adaptive Capacity Score
      (NACS). In conclusion, patients receiving midazolam 0.025 mg kg(-1) as
      premedication had significantly low anxiety scores, without any adverse effects
      on the newborns. Midazolam can therefore safely be used as a premedicative agent
      in C/S surgery.

PMID- 24565385
TI  - Preoperative evaluation of the patient with pulmonary disease.
AB  - BACKGROUND AND OBJECTIVES: In daily clinical practice, pulmonary complications
      related to surgical procedure are common, increasing the morbidity and mortality
      of patients. Assessment of the risk of pulmonary complications is an important
      step in the preoperative evaluation. Thus, we review the most relevant aspects of
      preoperative assessment of the patient with lung disease. CONTENT: Pulmonary risk
      stratification depends on clinical symptoms and patient's physical status. Age,
      preexisting respiratory diseases, nutritional status, and continued medical
      treatment are usually more important than additional tests. Pulmonary function
      tests are of great relevance when high abdominal or thoracic procedures are
      scheduled, particularly when lung resection are considered. CONCLUSION:
      Understanding the perioperative evaluation of the potential risk for developing
      pulmonary complication allows the medical team to choose the adequate anesthetic
      technique and surgical and clinical care required by each patient, thereby
      reducing adverse respiratory outcomes.

PMID- 24565386
TI  - Do metoclopramide and ondansetrone alter mivacurium-induced neuromuscular
      blockade? - a randomised trial.
AB  - BACKGROUND: We aimed to investigate the effects of metoclopramide and
      ondansetrone on mivacurium neuromuscular blockade. METHODS: Seventy five, ASA I
      II patients, aged 18-65 and scheduled for elective surgery requiring tracheal
      intubation were included in the study. The patients received metoclopramide 10
      mg, ondansetrone 4 mg or normal saline 5 mL; group M, group O, group NS (n=25),
      respectively. Before anesthesia study drugs were administered in a volume of 5
      mL. The level of plasma cholinesterase were obtained before and 5 minutes after
      the administration of study drugs and 5 minutes after the administration of
      mivacurium. Onset time, T25, T75, T25-75, T90 levels were compared with each
      other and differences between each patients were investigated. After recording
      T90, the study was terminated and surgery was started. RESULTS: Onset time was
      significantly shorter in group M, than the other two groups. Onset time in group
      O was significantly shorter than in group NS. In Group M T25, T75, T90 and
      recovery indices were significantly greater than in Group NS (p<0.001). In Group
      O T25, T75 were greater than Group NS (p<0.01 and p<0.05, respectively). In Group
      M T75, T90 and emergence indices were significantly higher than Group O (p<0.001,
      p<0.01, p<0.001, respectively). In Groups M and O, plasma cholinesterase levels
      decreased significantly (p<0.001) after administration of study drugs and
      mivacurium. Plasma cholinesterase also was reduced in Group NS 5 minutes after
      the administration of mivacurium (p<0.001). CONCLUSION: Ondansetrone is believed
      to be more reliable agent than metoclopramide when used with mivacurium.

PMID- 24565387
TI  - Intravenous clonidine administration and its ability to reduce pulmonary arterial
      pressure in patients undergoing heart surgery.
AB  - OBJECTIVE: Evaluate the ability of clonidine to reduce pulmonary arterial
      pressure in patients with pulmonary hypertension undergoing heart surgery, either
      by reducing the pressure values from the direct measurement of pulmonary arterial
      pressure or by reducing or eliminating the need for intraoperative dobutamine and
      nitroprusside. METHOD: Randomized, double-blind, placebo-controlled, comparative
      study conducted in 30 patients with pulmonary arterial hypertension type 2
      undergoing cardiac surgery. Mean pulmonary arterial pressure and dosage of
      dobutamine and sodium nitroprusside were assessed four times: before intravenous
      administration of clonidine (2 MUg/kg) or placebo (T0), 30 min after tested
      treatment and before cardiopulmonary bypass (T1), immediately after CPB (T2), 10
      min after protamine injection (T3). RESULTS: There were no significant
      differences regarding mean pulmonary arterial pressure at any time of evaluation.
      There was no significant difference between groups regarding other variables,
      such as mean systemic arterial pressure, heart rate, total dose of dobutamine,
      total dose of sodium nitroprusside, and need for fentanyl. CONCLUSION: Data
      analysis from patients included in this study allows us to conclude that
      intravenous clonidine (2 MUg/kg) was not able to reduce the mean pulmonary
      arterial pressure in patients with pulmonary hypertension in group 2 (pulmonary
      venous hypertension), undergoing heart surgery, or reduce or eliminate the need
      for intraoperative administration of dobutamine and sodium nitroprusside.

PMID- 24565388
TI  - Determination of the minimum effective volume of 0.5% bupivacaine for ultrasound
      guided axillary brachial plexus block.
AB  - BACKGROUND AND OBJECTIVE: The use of ultrasound for needle correct placement and
      local anesthetic spread monitoring helped to reduce the volume of local
      anesthetic required for peripheral nerve blocks. There are few studies of the
      minimum effective volume of local anesthetic for axillary brachial plexus block.
      The aim of this study was to determine the minimum effective volume (VE90) of
      0.5% bupivacaine with epinephrine (1:200,000) for ultrasound guided ABPB. METHOD:
      Massey and Dixon's up-and-down method was used to calculate the minimum effective
      volume. The initial dose was 5 mL per nerve (radial, median, ulnar, and
      musculocutaneous). In case of blockade failure, the volume was increased to 0.5
      mL per nerve. A successful blockade resulted in decreased volume of 0.5 mL per
      nerve to the next patient. Successful blockade was defined as a motor block <=2,
      according to the modified Bromage scale; lack of thermal sensitivity; and
      response to pinprick. The achievement of five cases of failure followed by
      success cases was defined as criterion to complete the study. RESULTS: 19
      patients were included in the study. The minimum effective volume (VE90) of 0.5%
      bupivacaine with 1:200,000 epinephrine was 1.56 mL (95% CI, 0.99-3.5) per nerve.
      CONCLUSION: This study is in agreement with some other studies, which show that
      it is possible to achieve surgical anesthesia with low volumes of local
      anesthetic for ultrasound-guided peripheral nerve blocks.

PMID- 24565389
TI  - Indication of preoperative tests according to clinical criteria: need for
      supervision.
AB  - BACKGROUND AND OBJECTIVES: The indiscriminate order for additional tests on pre
      anesthetic evaluation is common in clinical practice, which entails additional
      costs and the possibility of false-positive results. The aim of this study was to
      analyze whether preoperative tests in elective surgeries are ordered according to
      clinical criteria and assess the unnecessary costs for the institution. METHODS:
      Evaluation of preoperative investigations in adult patients undergoing elective
      non-cardiac surgery. Tests were ordered by surgeons according to the Anesthesia
      Service protocol. Demographic data, physical status, comorbidities, and type of
      ordered supplementary examination were evaluated. The tests performed were
      compared with the indicated tests. The cost of screening was based on Datasus'
      table. RESULTS: 1063 patients were evaluated. It was found that 41.9% of the
      tests performed on patients classified as ASA-I were not indicated. In ASA II
      group, 442 tests (17.72%) were made unnecessarily. The ordered percentages of
      blood count, creatinine, coagulation profile, chest X-ray, and ECG were high in
      groups ASA I-II. Only 40 (5.25%) of the examinations made in ASA III group were
      not indicated. In ASA IV group, 22.5% of the required tests were not performed.
      We highlight an annual saving of 13% (R$ 1923.13) if tests were done according to
      the protocol. CONCLUSIONS: Preoperative tests are not always ordered according to
      clinical criteria, which results in higher costs for the institution.

PMID- 24565390
TI  - Effectiveness of the C-MAC video laryngoscope in the management of unexpected
      failed intubations.
AB  - BACKGROUND AND OBJECTIVES: The purpose of this study was to review the
      experiences of an anesthesiology department regarding the use of a C-MAC
      videolaryngoscope in unexpected failed intubation attempts. METHODS: Data were
      analyzed from 42 patients whose intubation attempts using Macintosh direct
      laryngoscopes had failed, and on whom a C-MAC videolaryngoscope was utilized as
      the primary rescue device. The success rate of C-MAC in intubation was assessed,
      and laryngeal views from both devices were compared. RESULTS: The Cormack and
      Lehane score was III in 41 patients, and IV in one patient, with the Macintosh
      laryngoscope, while Cormack and Lehane score was I in 27 patients, II in 14 and
      III in one with CMAC. Tracheal intubation with CMAC was successful on the first
      attempt in 36 patients (86%), and on the second attempt in 6 patients (14%). No
      complications were observed other than minor damage (blood on blade) in 8
      patients (19%). CONCLUSION: These data provide evidence for the clinical
      effectiveness of C-MAC videolaryngoscope in managing the unexpected failed
      intubations in routine anesthesia care. The C-MAC videolaryngoscope is efficient
      and safe as a primary rescue device in unexpected failed intubations.

PMID- 24565391
TI  - Can SupremeTM laryngeal mask airway be an alternative to endotracheal intubation
      in laparoscopic surgery?
AB  - BACKGROUND AND OBJECTIVES: In laparoscopic surgical procedures, experts recommend
      tracheal intubation for airway management. Laryngeal mask airway (LMA) can be a
      good alternative to intubation. In this case series, we aimed to examine the use
      of the SupremeTM LMA (SLMA) in laparoscopic surgical practice. METHODS: We
      planned the study for sixty patients between the ages of 18 and 60, who would
      undergo laparoscopic surgery. We recorded one, 15, 30, 45, and 60-minute
      peripheral O2 saturation (SpO2) and end-tidal carbon dioxide (EtCO2) values,
      heart rate and mean arterial blood pressure (MAP). We observed the duration of
      SLMA insertion, the rate of gastric tube applicability, whether nausea, vomiting,
      and coughing developed, and whether there was postoperative 1-hour sore throat.
      RESULTS: The initial EtCO2 mean was lower than the EtCO2 means of 15, 30, 45, and
      60 minutes (p < 0.0001) and the 15-minute EtCO2 mean was lower than other
      measured EtCO2 means. We observed the initial heart rate mean to be higher than
      the ones following the SLMA insertion, prior to the SLMA removal, and after the
      SLMA removal. The heart rate mean after the SLMA insertion was remarkably lower
      than the heart rate mean prior to the SLMA removal (p=0.013). The MAP after the
      SLMA insertion was lower than the initial MAP means, as well as the MAP averages
      prior to after the removal of SLMA (p=0.0001). CONCLUSION: SLMA can be a suitable
      alternative to intubation in laparoscopic surgical procedures in a group of
      selected patients.

PMID- 24565392
TI  - The use of laryngeal mask airway in tonsillectomies.

PMID- 24565393
TI  - The use of laryngeal mask airway in tonsillectomies. Reply to Alper Nabi Erkan.

PMID- 24565394
TI  - A framework for biomedical figure segmentation towards image-based document
      retrieval.
AB  - The figures included in many of the biomedical publications play an important
      role in understanding the biological experiments and facts described within.
      Recent studies have shown that it is possible to integrate the information that
      is extracted from figures in classical document classification and retrieval
      tasks in order to improve their accuracy. One important observation about the
      figures included in biomedical publications is that they are often composed of
      multiple subfigures or panels, each describing different methodologies or
      results. The use of these multimodal figures is a common practice in bioscience,
      as experimental results are graphically validated via multiple methodologies or
      procedures. Thus, for a better use of multimodal figures in document
      classification or retrieval tasks, as well as for providing the evidence source
      for derived assertions, it is important to automatically segment multimodal
      figures into subfigures and panels. This is a challenging task, however, as
      different panels can contain similar objects (i.e., barcharts and linecharts)
      with multiple layouts. Also, certain types of biomedical figures are text-heavy
      (e.g., DNA sequences and protein sequences images) and they differ from
      traditional images. As a result, classical image segmentation techniques based on
      low-level image features, such as edges or color, are not directly applicable to
      robustly partition multimodal figures into single modal panels. In this paper, we
      describe a robust solution for automatically identifying and segmenting unimodal
      panels from a multimodal figure. Our framework starts by robustly harvesting
      figure-caption pairs from biomedical articles. We base our approach on the
      observation that the document layout can be used to identify encoded figures and
      figure boundaries within PDF files. Taking into consideration the document layout
      allows us to correctly extract figures from the PDF document and associate their
      corresponding caption. We combine pixel-level representations of the extracted
      images with information gathered from their corresponding captions to estimate
      the number of panels in the figure. Thus, our approach simultaneously identifies
      the number of panels and the layout of figures. In order to evaluate the approach
      described here, we applied our system on documents containing protein-protein
      interactions (PPIs) and compared the results against a gold standard that was
      annotated by biologists. Experimental results showed that our automatic figure
      segmentation approach surpasses pure caption-based and image-based approaches,
      achieving a 96.64% accuracy. To allow for efficient retrieval of information, as
      well as to provide the basis for integration into document classification and
      retrieval systems among other, we further developed a web-based interface that
      lets users easily retrieve panels containing the terms specified in the user
      queries.

PMID- 24565395
TI  - Handheld ultrasound devices and the training conundrum: how to get to "seeing is
      believing".

PMID- 24565396
TI  - Left ventricular outflow tract velocities-all in context.

PMID- 24565397
TI  - Authors' reply.

PMID- 24565398
TI  - Heralding our legislative successes.

PMID- 24565400
TI  - The 25th Annual ASE Scientific Sessions-The Pediatric & Congenital Heart Disease
      Program Will Show You the Future and Celebrate Our Past.

PMID- 24565399
TI  - Ergonomics-taking care of yourself.

PMID- 24565401
TI  - Propensity score matching analysis of mechanical versus bioprosthetic tricuspid
      valve replacements.
AB  - BACKGROUND: Evidence for optimal prosthesis in the tricuspid position is lacking.
      We compared long-term results of tricuspid valve replacement (TVR) using
      mechanical and bioprosthetic valves. METHODS: From January 1994 to December 2012,
      224 patients (male to female ratio=55:169) underwent TVR. Mechanical TVR was
      performed in 121 patients (MTV group), and 103 patients underwent bioprosthetic
      TVR (BTV group). Patients in the BTV group were older and more frequently had
      hypertension than those in the MTV group. Propensity score matching was
      performed, and 66 patients were extracted from each group. Median follow-up
      duration was 73 (1 to 235) months. Operative results, long-term survival, and
      tricuspid valve-related events (TVRE) were compared. RESULTS: The ages of the
      propensity score-matched patients were 54.1+/-8.7 and 55.3+/-11.6 years in the
      MTV and BTV groups, respectively. Early mortality (n=9, 6.8%) and postoperative
      complications were similar between the propensity score-matched groups. The 10
      year overall survival and freedom from cardiac death rates were similar between
      the 2 matched groups (p=0.897 and p=0.893, respectively). Freedom rates from a
      composite of thromboembolism and bleeding were lower in the MTV group than in the
      BTV group (83.6% and 77.4% vs 89.5% and 89.5% at 5 and 10 years, respectively),
      although it was not statistically significant. The TVRE-free rates at 10 years
      were 54.8% and 53.6% in the MTV and BTV groups, respectively. CONCLUSIONS:
      Bioprosthetic valve replacement is a valid option for TVR in these relatively
      young patients because anticoagulation could be avoided without increasing the
      risks of long-term TVRE.

PMID- 24565403
TI  - Increased aorto-mitral curtain thickness independently predicts mortality in
      patients with radiation-associated cardiac disease undergoing cardiac surgery.
AB  - BACKGROUND: Thoracic radiation leads to radiation-associated cardiac disease
      (RACD), associated with substantial cardiac morbidity and mortality, often
      requiring complex cardiothoracic surgery. In patients with RACD, along with
      valvular lesions, the aorto-mitral curtain (AMC, junction between base of
      anterior mitral leaflet and aortic root) thickness is increased on transthoracic
      echocardiography. We sought to identify clinical and transthoracic
      echocardiography predictors of long-term mortality in patients with RACD.
      METHODS: We studied 173 patients with RACD (75% women, 63+/-14 years, 53% with
      breast cancer, 27% with Hodgkin lymphoma; mean time from radiation, 18+/-12
      years), who underwent cardiothoracic surgery (26% redo) between 2000 and 2003.
      Clinical, transthoracic echocardiography (along with AMC), and surgical variables
      were recorded. Preoperative EuroSCORE and all-cause mortality were recorded.
      RESULTS: Mean left ventricular ejection fraction, right systolic ventricular
      pressure, and AMC thickness were 0.49+/-0.13, 41+/-15 mm Hg, and 0.54+/-0.2 cm,
      respectively. Fifty-one percent of patients had II+ mitral regurgitation or
      greater, 29% patients had II+ aortic regurgitation or greater, 23% patients had
      severe aortic stenosis, and 34% patients had II+ tricuspid regurgitation or
      greater. In 7.6+/-3 years of follow-up, there were 95 (55%) deaths, with a 30-day
      mortality rate of only 7 (4%). Absence of beta-blockers (hazard ratio, 0.49; 95%
      confidence interval, 0.31 to 0.79), aspirin (hazard ratio, 0.53; 95% confidence
      interval, 0.33 to 0.84), higher EuroSCORE (hazard ratio, 1.11; 95% confidence
      interval, 1.02 to 1.21), and greater AMC thickness (hazard ratio, 5.75; 95%
      confidence interval, 1.57 to 21.03; all p<0.01) independently predicted
      mortality. Aorto-mitral curtain thickness of at least 0.6 cm was associated with
      significantly increased mortality. CONCLUSIONS: Patients with RACD undergoing
      cardiothoracic surgery have high long-term mortality, which is independently
      predicted by AMC thickness, a higher preoperative risk score, and lack of
      cardioprotective medications.

PMID- 24565402
TI  - Proteomic study reveals plasma protein changes in congenital heart diseases.
AB  - BACKGROUND: Congenital heart disease (CHD) is the most common birth defect in
      newborns. Plasma proteins may serve as indicators of disease and are a rich
      source for biomarker discovery, but little has been studied in CHD. We examined
      the hypothesis that plasma proteins may be altered and related to the pathologic
      changes of CHD. METHODS: Differential protein analysis was performed in the
      plasma of patients with tetralogy of Fallot, isolated ventricular septal defect,
      and normal controls by using two-dimensional electrophoresis and mass
      spectrometry. Candidate proteins that might be related to disease processes were
      further confirmed by enzyme-linked immunosorbent assay in the new samples (n=40).
      RESULTS: Identified were 18 differentially expressed protein spots and 10
      corresponding proteins or polypeptides. Among those, 2 downregulated proteins,
      gelsolin, ficolin-3, with significant clinical relevance, were further analyzed
      for validation. The plasma levels of gelsolin (76.30+/-4.42 vs 131.80+/-23.46
      MUg/mL in control; p=0.025, n=40 in each group) and ficolin-3 (4.93+/-0.36 vs
      10.58+/-1.58 MUg/mL in control; p=0.001, n=40 in each group) in tetralogy
      patients were significantly lower than those in normal controls. The ficolin-3
      plasma level was also lower in the patients with isolated VSD (5.55+/-0.34 vs
      10.58+/-1.58 MUg/mL in control MUg/mL; p=0.003, n=40 in each group). CONCLUSIONS:
      We used proteomic methods to demonstrate for the first time the plasma protein
      changes in CHD patients that may reveal the possible mechanisms for the prolonged
      bleeding time in tetralogy patients and the susceptibility to pulmonary
      infections in patients with CHDs. These findings have strong clinical
      implications.

PMID- 24565404
TI  - Prognostic analysis for survival after resections of localized primary cardiac
      sarcomas: a single-institution experience.
AB  - BACKGROUND: Primary cardiac sarcomas are rare diseases with a poor prognosis.
      This study aims to provide a prognostic analysis after different levels of
      resections of cardiac sarcomas. METHODS: Twenty-nine patients undergoing
      resections of primary cardiac sarcomas at the Zhongshan Hospital from September
      1995 to July 2012 were retrospectively reviewed. RESULTS: There were 15 women and
      14 men. The mean age was 41.0 years. The most common histologic type was
      angiosarcoma (28%). The median survival for the entire cohort was 17 months
      (range, 5 to 216 months). Patients with microscopically negative margin (R0)
      resections had a better median survival than those with microscopically positive
      margin (R1) resections (58 months versus 11 months; p<0.001). The median survival
      after an R1 resection was not different from that after a partial resection (12
      months; p=0.81). The median local recurrence-free survival after an R0 resection
      was longer than that after an R1 resection (36 months versus 6 months; p<0.001).
      Five patients who underwent R0 resections and repeated resections of local
      recurrences or metastases had the longest median survival of 72 months. None of
      the patients with R0 resections received adjuvant therapy. Multimodality
      treatment after R1 and partial resections slightly increased the survival.
      CONCLUSIONS: For nonmetastatic and localized primary cardiac sarcoma, an R0
      surgical resection of cardiac sarcomas should be performed. Aggressive surgical
      treatment or radiation therapy for local recurrence or metastasis prolongs the
      survival. Multimodality treatment is recommended after incomplete resections of
      cardiac sarcomas. The role of adjuvant chemotherapy after R0 resections is
      unclear.

PMID- 24565405
TI  - Prediction of major cardiovascular events after lung resection using a modified
      scoring system.
AB  - BACKGROUND: Cardiovascular complications occur in 10% to 15% of patients after
      major lung resection. We evaluated the utility of a revised scoring system
      (thoracic revised cardiac risk index; ThRCRI) in identifying patients at
      increased risk for major cardiovascular complications. METHODS: We analyzed
      outcomes from the Society of Thoracic Surgeons General Thoracic Database for the
      period 2003 to 2011 for elective major lung resection. The ThRCRI risk score was
      based on weighted values for serum creatinine, coronary artery disease,
      cerebrovascular disease, and extent of lung resection, and was stratified into
      the following 4 risk categories: 0 (A); 1 to 1.5 (B); 2 to 2.5 (C); and >2.5 (D).
      Major cardiovascular complications included myocardial infarction, adult
      respiratory distress syndrome, ventricular arrhythmia requiring treatment, and
      all-cause death. RESULTS: A total of 26,085 patients (mean age 65.4+/-11.4 years;
      51.3% men) underwent lobectomy (21,679; 83.2%), bilobectomy (1,446; 5.5%) or
      pneumonectomy (1,697; 6.5%). Major cardiovascular complications occurred in 1,125
      patients (4.3%). ThRCRI scores in patients without and with major cardiovascular
      complications were 0.6+/-0.9 and 1.1+/-1.1 (p<0.0001). Score categories yielded
      incremental risks of major cardiovascular complications (A: 2.9%; B: 5.8%; C:
      11.9%; D: 11.1%; p<0.0001). CONCLUSIONS: The ThRCRI score stratified risk
      moderately well for major postoperative cardiovascular events after major lung
      resection. Use of this scoring system might help in identifying patients who
      would benefit from additional preoperative evaluation and from closer
      perioperative monitoring.

PMID- 24565406
TI  - JAK3 inhibition: what potential for the future?
AB  - JAK3 inhibition with the CP-690,550 compound has an immunosuppressive potency in
      murine models, nonhuman primates and humans. This drug blocks STAT5 activation in
      most T-cell subpopulations but less effectively in T-regulator cells. In low to
      moderate risk human kidney transplant recipients, combined with mycophenolate
      mofetil, steroids and an induction with basiliximab, CP-690,550 proved as
      effective as calcineurin inhibitors with regard to prevention of acute rejection
      but better than calcineurin inhibitors with regard to preservation of kidney
      function and histology. However, at the same time, an increased incidence of
      overimmunosuppression consequences (cytomegalovirus, BK virus and
      lymphoproliferation) was observed and led to discontinuation of this specific
      drug development in kidney transplantation. 

PMID- 24565407
TI  - Knowledge translation: an overview and recommendations in relation to the Fourth
      Canadian Consensus Conference on the Diagnosis and Treatment of Dementia.
AB  - The growing population of persons with dementia in Canada and the provision of
      quality care for this population is an issue that no healthcare authority will
      escape. Physicians often view dementia as a difficult and time-consuming
      condition to diagnose and manage. Current evidence must be effectively
      transformed into usable recommendations for physicians; however, we know that use
      of evidence-based practice recommendations is a challenge in all realms of
      medical care, and failure to utilize these leads to less than optimal care for
      patients. Despite this expanding need for readily available resources, knowledge
      translation (KT) is often seen as a daunting, if not confusing, undertaking for
      researchers. Here we offer a brief introduction to the processes around KT,
      including terms and definitions, and outline some common KT frameworks including
      the knowledge to action cycle, the Promoting Action on Research Implementation in
      Health Services framework and the Consolidated Framework for Implementation
      Research. We also outline practical steps for planning and executing a KT
      strategy particularly around the implementation of recommendations for practice,
      and offer recommendations for KT planning in relation to the Fourth Canadian
      Consensus Conference on the Diagnosis and Treatment of Dementia. 

PMID- 24565409
TI  - Active enhancer positions can be accurately predicted from chromatin marks and
      collective sequence motif data.
AB  - BACKGROUND: Transcriptional regulation in multi-cellular organisms is a complex
      process involving multiple modular regulatory elements for each gene. Building
      whole-genome models of transcriptional networks requires mapping all relevant
      enhancers and then linking them to target genes. Previous methods of enhancer
      identification based either on sequence information or on epigenetic marks have
      different limitations stemming from incompleteness of each of these datasets
      taken separately. RESULTS: In this work we present a new approach for discovery
      of regulatory elements based on the combination of sequence motifs and epigenetic
      marks measured with ChIP-Seq. Our method uses supervised learning approaches to
      train a model describing the dependence of enhancer activity on sequence features
      and histone marks. Our results indicate that using combination of features
      provides superior results to previous approaches based on either one of the
      datasets. While histone modifications remain the dominant feature for accurate
      predictions, the models based on sequence motifs have advantages in their general
      applicability to different tissues. Additionally, we assess the relevance of
      different sequence motifs in prediction accuracy showing that even tissue
      specific enhancer activity depends on multiple motifs. CONCLUSIONS: Based on our
      results, we conclude that it is worthwhile to include sequence motif data into
      computational approaches to active enhancer prediction and also that classifiers
      trained on a specific set of enhancers can generalize with significant accuracy
      beyond the training set.

PMID- 24565408
TI  - Rift Valley fever in Kedougou, southeastern Senegal, 2012.

PMID- 24565410
TI  - Bacterial ligand stimulates TLR2-dependent chemokines of colon cell.
AB  - Shigella spp. are known to penetrate the colonic epithelial cells causing
      shigellosis, which results in production of convalescent antibodies against
      porin, the surface exposed major outer membrane protein. Porin has been
      categorized as primarily TLR2-ligand and here we validated its signaling
      procedure in colonic INT-407 cells simulating the host scenario. Porin up
      regulated TLR2 and -6 followed by TLR2.MYD88 complex formation suggesting direct
      involvement of MYD88 for downstream signaling. Translocation of NF-kappaB p65 and
      p50 subunits on to the nucleus indicates involvement of the transcription factor
      in signaling. Porin-induced TLR signaling specifically stimulated the pro
      inflammatory chemokine panel comprising of MIP-1alpha, MCP-1 and IL-8. Inhibition
      studies of TLR2 and NF-kappaB led to abrogation of the pro-inflammatory chemokine
      response, showing TLR-dependent signaling through NF-kappaB regulate gut
      activity. This work elucidates TLR2 not only scans pathogen-associated molecule
      but also has a direct role in maneuvering colon cell response. 

PMID- 24565411
TI  - Extraction of (129)I and (127)I via combustion from organic rich samples using
      (125)I as a quantitative tracer.
AB  - Iodine-129 ((129)I) is a biophilic, naturally occurring radioisotope (half-life:
      1.57 * 10(7) years) that has been released in large quantities by nuclear fuel
      reprocessing. This iodine has cycled throughout the globe and chiefly the
      northern hemisphere and can be found in a wide variety of environmental
      materials, particularly organic rich soil and organic matter. Extracting iodine
      reliably from solid samples has been done by a variety of methods, however,
      pyrohydrolysis has been the most widely used. There is a wide variation between
      existing pyrohydrolysis techniques and this raises questions about the
      quantitative recovery of iodine from method to method. In order to quantify
      iodine recovery from pyrohydrolysis we have spiked samples with an iodine-125
      radiotracer prior to combustion and trapping in an alkaline solution. Inorganic
      (125)I tracer was used as well as humic acid labeled with (125)I to simulate the
      behavior of (129)I and (127)I in complex organic substances and extract iodine
      regardless of how it is partitioned. Using these tracers we explored the effect
      on recovery of (125)I under a variety of combustion parameters. These include
      carrier gas flow rate and iodine volatilization temperature. We observed that the
      best recoveries of (125)I were at flow rates between 400 and 800 mL/min and most
      (125)I recoveries were above 85%. The experiment to determine the temperature at
      which iodine volatilizes from the sample showed two distinct trends for the
      release of iodine. One trend showed that most iodine is released at approximately
      525  degrees C, while the other trend showed that the samples needed to reach 800
      degrees C and remain there for at least an hour. These findings illustrate the
      usefulness and importance of using a quantitative recovery tracer for every
      iodine extraction. We then combusted and precipitated several Atlantic Ocean
      seaweed and standard reference materials for AMS analysis as AgI. The (129)I
      concentration of the seaweed ranged between 4.4-5.5 * 10(9) atoms/g and the
      (129)I/(127)I ratio was 2.3-2.9 * 10(-9), both of which compare well to published
      values for Atlantic seaweed. The results for the standard reference materials
      also agree with specified values indicating that this technique is reliable. By
      optimizing pyrohydrolysis conditions and testing the recovery of iodine with a
      (125)I tracer it is possible to quantify and maximize recovery from organic
      samples. This will allow for the investigation of variations in the (129)I
      concentration and (129)I/(127)I ratio with a high degree of precision in complex,
      organic rich samples. 

PMID- 24565412
TI  - Continuum descriptions of cytoskeletal dynamics.
AB  - This tutorial presents an introduction into continuum descriptions of
      cytoskeletal dynamics. In contrast to discrete models in which each molecule
      keeps its identity, such descriptions are given in terms of averaged quantities
      per unit volume like the number density of a certain molecule. Starting with a
      discrete description for the assembly dynamics of cytoskeletal filaments, we
      derive the continuity equation, which serves as the basis of many continuum
      theories. We illustrate the use of this approach with an investigation of
      spontaneous cytoskeletal polymerization waves. Such waves have by now been
      observed in various cell types and might help to orchestrate cytoskeletal
      dynamics during cell spreading and locomotion. Our analysis shows how processes
      at the scale of single molecules, namely, the nucleation of new filaments and
      filament treadmilling, can lead to the spontaneous appearance of coherent
      traveling waves on scales spanning many filament lengths. For readers less
      familiar with calculus, we include an informal introduction to the Taylor
      expansion. 

PMID- 24565413
TI  - Reduced long-term exercise capacity in young adults operated for ventricular
      septal defect.
AB  - BACKGROUND: Ventricular septal defects are normally closed in early childhood,
      and post-surgically the patients are considered as healthy and fit as their
      peers. However, data are inconsistent. We exercise-tested a cohort of ventricular
      septal defect-operated patients and a group of matched controls to evaluate long
      term physical fitness. METHODS: Cardiopulmonary exercise capacity was tested on
      an ergometer cycle in 30 patients and 30 healthy age and gender-matched controls.
      Pulmonary ventilation and gas exchange were simultaneously measured breath-by
      breath with Jaeger MasterScreen CPX(r) (CareFusion, San Diego, United States of
      America). During the test session, respiratory gas exchange was measured along
      with heart rate, blood pressure, and electrocardiogram. The endpoints were peak
      oxygen uptake, maximal workload, and ventilatory anaerobic threshold. The
      International Physical Activity Questionnaire and the SF-36 were applied for
      Health-Related Quality-of-Life assessment. RESULTS: Ventricular septal defect
      operated adults had a markedly lower peak oxygen uptake: mean 38.0(+/-8.2 ml
      O2/kg/minute) versus 47.9(+/-6.5 ml O2/kg/minute) in controls, p<0.01.
      Furthermore, ventilatory anaerobic threshold was impaired in ventricular septal
      defect patients: mean 25.3(+/-7.8 ml O2/kg/minute) versus 35.2(+/-7.7 ml
      O2/kg/minute) in controls, p<0.01. Maximal workload was reduced: mean 3.3(+/-0.7
      W/kg) versus 4.0(+/-0.5 W/kg) in the control group, p<0.01. Lastly, ventricular
      septal defect patients had a significantly lower peak heart rate: mean 182(+/-8.8
      beats/minute) versus 188(+/-9.0 beats/minute) in controls, p=0.03. Regarding
      Health-Related Quality of Life, the ventricular septal defect group had
      significantly lower scores in physical functioning, role physical, and social
      functioning. CONCLUSION: Young adults with a surgically closed ventricular septal
      defect had a markedly reduced cardiopulmonary exercise capacity and a lower peak
      heart rate compared with controls.

PMID- 24565414
TI  - Mixed scrub typhus genotype, Shandong, China, 2011.

PMID- 24565415
TI  - Human induced pluripotent stem cell-based microphysiological tissue models of
      myocardium and liver for drug development.
AB  - Drug discovery and development to date has relied on animal models, which are
      useful but are often expensive, slow, and fail to mimic human physiology. The
      discovery of human induced pluripotent stem (iPS) cells has led to the emergence
      of a new paradigm of drug screening using human and disease-specific organ-like
      cultures in a dish. Although classical static culture systems are useful for
      initial screening and toxicity testing, they lack the organization of
      differentiated iPS cells into microphysiological, organ-like structures deemed
      necessary for high-content analysis of candidate drugs. One promising approach to
      produce these organ-like structures is the use of advanced microfluidic systems,
      which can simulate tissue structure and function at a micron level, and can
      provide high-throughput testing of different compounds for therapeutic and
      diagnostic applications. Here, we provide a brief outline on the different
      approaches, which have been used to engineer in vitro tissue constructs of iPS
      cell-based myocardium and liver functions on chip. Combining these techniques
      with iPS cell biology has the potential of reducing the dependence on animal
      studies for drug toxicity and efficacy screening. 

PMID- 24565416
TI  - Rational/antiemotional behaviors in interpersonal relationships and the
      functional prognosis of patients with rheumatoid arthritis: a Japanese
      multicenter, longitudinal study.
AB  - BACKGROUND: The repression of negative emotions is a personality factor that
      received considerable attention in the 1950-60s as being relevant to the onset
      and course of rheumatoid arthritis (RA). Despite subsequent, repeated criticisms
      of the cross-sectional nature of the earlier studies, even to date few
      prospective studies have been reported on this issue. This multicenter study
      prospectively examined if "rational and antiemotional" behavior
      (antiemotionality), characterized by an extreme tendency to suppress emotional
      behaviors and to rationalize negative experiences in conflicting interpersonal
      situations, is associated with the functional prognosis of patients with RA.
      METHODS: 532 patients with RA who regularly visited one of eight
      hospitals/clinics in Japan in 2000 were recruited for study. All completed a self
      administered baseline questionnaire about lifestyle and psychosocial factors
      including antiemotionality. Two years after, 460 (mean age, 56.1 years; 54 men
      and 406 women) of 471 patients who continued to visit the clinics agreed to take
      the follow-up questionnaire. The functional status of the patients was evaluated
      by rheumatologists based on the ACR classification system. RESULTS: A multiple
      logistic regression model that included baseline demographic, disease
      activity/severity-related, therapeutic, and socioeconomic factors as covariates
      found a tendency toward higher antiemotionality to be related to poorer
      functional status at follow-up. This relationship was not explained by lifestyle
      factors. CONCLUSIONS: Antiemotionality may be a prognostic factor for the
      functional status of patients with RA. This finding sheds light on a seemingly
      forgotten issue in the care of patients with RA.

PMID- 24565417
TI  - On an ensemble algorithm for clustering cancer patient data.
AB  - BACKGROUND: The TNM staging system is based on three anatomic prognostic factors:
      Tumor, Lymph Node and Metastasis. However, cancer is no longer considered an
      anatomic disease. Therefore, the TNM should be expanded to accommodate new
      prognostic factors in order to increase the accuracy of estimating cancer patient
      outcome. The ensemble algorithm for clustering cancer data (EACCD) by Chen et al.
      reflects an effort to expand the TNM without changing its basic definitions.
      Though results on using EACCD have been reported, there has been no study on the
      analysis of the algorithm. In this report, we examine various aspects of EACCD
      using a large breast cancer patient dataset. We compared the output of EACCD with
      the corresponding survival curves, investigated the effect of different settings
      in EACCD, and compared EACCD with alternative clustering approaches. RESULTS:
      Using the basic T and N definitions, EACCD generated a dendrogram that shows a
      graphic relationship among the survival curves of the breast cancer patients. The
      dendrograms from EACCD are robust for large values of m (the number of runs in
      the learning step). When m is large, the dendrograms depend on the linkage
      functions. The statistical tests, however, employed in the learning step have
      minimal effect on the dendrogram for large m. In addition, if omitting the step
      for learning dissimilarity in EACCD, the resulting approaches can have a degraded
      performance. Furthermore, clustering only based on prognostic factors could
      generate misleading dendrograms, and direct use of partitioning techniques could
      lead to misleading assignments to clusters. CONCLUSIONS: When only the
      Partitioning Around Medoids (PAM) algorithm is involved in the step of learning
      dissimilarity, large values of m are required to obtain robust dendrograms, and
      for a large m EACCD can effectively cluster cancer patient data.

PMID- 24565419
TI  - Identification of b-/y-ions in MS/MS spectra using a two stage neural network.
AB  - Independent of the approach used, the ability to correctly interpret tandem MS
      data depends on the quality of the original spectra. Even in the case of the
      highest quality spectra, the majority of spectral peaks can not be reliably
      interpreted. The accuracy of sequencing algorithms can be improved by filtering
      out such 'noise' peaks. Preprocessing MS/MS spectra to select informative ion
      peaks increases accuracy and reduces the processing time. Intuitively, the mix of
      informative versus non-informative peaks has a direct effect on the quality and
      size of the resulting candidate peptide search space. As the number of selected
      peaks increases, the corresponding search space increases exponentially. If we
      select too few peaks then the ion-ladder interpretation of the spectrum will
      contain gaps that can only be explained by permutations of combinations of amino
      acids. This will result in a larger candidate peptide search space and poorer
      quality candidates. The dependency that peptide sequencing accuracy has on an
      initial peak selection regime makes this preprocessing step a crucial facet of
      any approach, whether de novo or not, to MS/MS spectra interpretation. 

PMID- 24565418
TI  - The effect of unhealthy beta-cells on insulin secretion in pancreatic islets.
AB  - BACKGROUND: Insulin secreted by pancreatic islet beta-cells is the principal
      regulating hormone of glucose metabolism and plays a key role in controlling
      glucose level in blood. Impairment of the pancreatic islet function may cause
      glucose to accumulate in blood, and result in diabetes mellitus. Recent studies
      have shown that mitochondrial dysfunction has a strong negative effect on insulin
      secretion. METHODS: In order to study the cause of dysfunction of pancreatic
      islets, a multiple cell model containing healthy and unhealthy cells is proposed
      based on an existing single cell model. A parameter that represents the function
      of mitochondria is modified for unhealthy cells. A 3-D hexagonal lattice
      structure is used to model the spatial differences among beta-cells in a
      pancreatic islet. The beta-cells in the model are connected through direct
      electrical connections between neighboring beta-cells. RESULTS: The simulation
      results show that the low ratio of total mitochondrial volume over cytoplasm
      volume per beta-cell is a main reason that causes some mitochondria to lose their
      function. The results also show that the overall insulin secretion will be
      seriously disrupted when more than 15% of the beta-cells in pancreatic islets
      become unhealthy. CONCLUSION: Analysis of the model shows that the insulin
      secretion can be reinstated by increasing the glucokinase level. This new
      discovery sheds light on antidiabetic medication.

PMID- 24565420
TI  - Anti-inflammatory response following uptake of apoptotic bodies by meningothelial
      cells.
AB  - BACKGROUND: Meningothelial cells (MECs) are the cellular components of the
      meninges. As such, they provide important barrier function for the central
      nervous system (CNS) building the interface between neuronal tissue and the
      cerebrospinal fluid (CSF), and are also part of the immune response of the CNS.
      METHODS: Human, immortalized MECs were analyzed by flow cytometry and confocal
      microscopy to study the uptake of apoptotic cells. Furthermore, cytokine and
      chemokine production by MECs was analyzed by cytokine array and ELISA. RESULTS:
      We found that MECs are highly active phagocytes able of ingesting and digesting
      large amounts of apoptotic cells. Furthermore, the uptake of apoptotic cells by
      MECs was immune suppressive via inhibiting the secretion of pro-inflammatory and
      chemoattractant cytokines and chemokines IL-6, IL-8, IL-16, MIF, and CXCL1, while
      increasing the secretion of anti-inflammatory IL-1 receptor antagonist by MECs.
      CONCLUSION: MECs respond with the secretion of anti-inflammatory cytokines and
      chemokines following the uptake of apoptotic cells potentially connecting these
      cells to processes important for the shut-down of immune responses in the brain.

PMID- 24565422
TI  - Surveillance of antimalarial drug resistance in China in the 1980s-1990s.
AB  - Since the successful preparation of the microplates and the medium for field
      application, the resistance degree and its geographical distribution of
      chloroquine-resistant Plasmodium falciparum, the fluctuation of the resistance
      degree of P. falciparum to chloroquine, and the sensitivity of the parasite to
      commonly used antimalarial drugs were investigated between 1980 and 2003 by the
      in vitro microtest and the in vivo four-week test recommended by the World Health
      Organization (WHO). The results indicated that chloroquine-resistant falciparum
      malaria was present in all eight provinces/autonomous regions endemic for
      falciparum malaria in China, and the resistance was high and widely distributed
      in the Hainan and Yunnan provinces. When the use of chloroquine was stopped or
      administered in a decreased quanity, the drug resistance gradually decreased. In
      Hainan and Yunnan, P. falciparum was still highly resistant to chloroquine,
      amodiaquine and piperaquine, and sensitive to pyronaridine and artemisinin
      derivatives, but the sensitivity was gradually reduced. Based on these results,
      principles and therapeutic regimens for antimalarial drug use in China were
      formulated, the use of the antimalarials which had already developed resistance
      was stopped or reduced, and recommendations to use artemisinin derivatives or
      compound pyronaridine to promote a rational use of antimalarials and strengthen
      malaria control were made. The results showed that malaria incidence had
      declined, and endemic areas of falciparum malaria have been gradually reducing
      since the mid-1980s. 

PMID- 24565421
TI  - Musculoskeletal disorder risk factors among nursing professionals in low resource
      settings: a cross-sectional study in Uganda.
AB  - BACKGROUND: Musculoskeletal disorders (MSD) constitute one of the main
      occupational hazards among health care workers. However, few epidemiological
      studies on work related MSD among nursing professionals have been carried out in
      Africa. The purpose of this study was to assess the work related musculoskeletal
      disorders and associated risk factors among nursing professionals in Uganda.
      METHODS: This was a cross-sectional study of MSD among 880 nursing professionals
      from five selected hospitals in Uganda. Data was collected using a questionnaire
      adapted from the Dutch Musculoskeletal and Nordic Musculoskeletal questionnaires.
      Descriptive (mean, standard deviation and percentages) and inferential (Chi
      square test and logistic regression analysis) statistics were used to analyse
      data. Alpha level was set at p < 0.05. RESULTS: A total of 741 completed
      questionnaires were analysed (response rate 85.4%). The average age of the
      respondents was 35.4 (SD 10.7) years and a majority were female (85.7%). The
      average working hours per week was 43.7 (SD 18.9 hours). The 12-month period
      prevalence of MSD at anybody site was 80.8%. The most common site of MSD was the
      lower back (61.9%). Significant risk factors for reported MSD included often
      working in a slightly bent posture (adjOR 2.25, 95% CI 1.20-4.26), often working
      in a slightly twisted posture for long (adjOR 1.97, 95% CI 1.03-3.77), mental
      exhaustion (adjOR 2.05, 95% CI 1.17-3.5), being absent from the work station for
      more than 6 months due to illness or an accident (adjO|R, 4.35, 95% CI 1.44
      13.08) and feeling rested after a break (adjOR 2.09, 95% CI 1.16-3.76).
      CONCLUSIONS: Musculoskeletal disorders affect more than 80% of nursing
      professionals in Uganda with the most commonly, affected site being the lower
      back. Significant risk factors for MSD include; being absent from the work
      station for more than 6 months due to illness or an accident, working in awkward
      postures, pushing/pulling of heavy loads and mental exhaustion. There is a need
      for greater advocacy, better working conditions and adoption of strategies to
      reduce occupational injuries.

PMID- 24565423
TI  - Concomitant multidrug-resistant pulmonary tuberculosis and susceptible
      tuberculous meningitis.

PMID- 24565424
TI  - Pertussis: a persistent cause of morbidity and mortality in young infants.
AB  - In 2012, a pertussis outbreak in Dallas County resulted in the deaths of 4
      children (3, unvaccinated; 2, <60 days of age). Despite recommendations that
      include immunization of women preferably during the third trimester of pregnancy
      or postpartum, household contacts ("cocooning"), and infants as early as 42 days
      of age, challenges in pertussis prevention remain. 

PMID- 24565426
TI  - The "glacier crevice" sign, from image to diagnosis.

PMID- 24565425
TI  - Effect of Hispanic ethnicity and language barriers on appendiceal perforation
      rates and imaging in children.
AB  - OBJECTIVE: To determine the association between Hispanic ethnicity and limited
      English proficiency (LEP) and the rates of appendiceal perforation and advanced
      radiologic imaging (computed tomography and ultrasound) in children with
      abdominal pain. STUDY DESIGN: We performed a secondary analysis of a prospective,
      cross-sectional, multicenter study of children aged 3-18 years presenting with
      abdominal pain concerning for appendicitis between March 2009 and April 2010 at
      10 tertiary care pediatric emergency departments in the US. Appendiceal
      perforation and advanced imaging rates were compared between ethnic and language
      proficiency groups using simple and multivariate regression models. RESULTS: Of
      2590 patients enrolled, 1001 (38%) had appendicitis, including 36% of non
      Hispanics and 44% of Hispanics. In multivariate modeling, Hispanics with LEP had
      a significantly greater odds of appendiceal perforation (OR, 1.44; 95% CI, 1.20
      1.74). Hispanics with LEP with appendiceal perforation of moderate clinical
      severity were less likely to undergo advanced imaging compared with English
      speaking non-Hispanics (OR, 0.64; 95% CI, 0.43-0.95). CONCLUSION: Hispanic
      ethnicity with LEP is an important risk factor for appendiceal perforation in
      pediatric patients brought to the emergency department with possible
      appendicitis. Among patients with moderate clinical severity, Hispanic ethnicity
      with LEP appears to be associated with lower imaging rates. This effect of
      English proficiency and Hispanic ethnicity warrants further investigation to
      understand and overcome barriers, which may lead to increased appendiceal
      perforation rates and differential diagnostic evaluation.

PMID- 24565429
TI  - The 30-minute standard: how fast is fast enough?

PMID- 24565430
TI  - Safe prevention of the primary cesarean delivery.
AB  - In 2011, 1 in 3 women who gave birth in the United States did so by cesarean
      delivery. Cesarean birth can be lifesaving for the fetus, the mother, or both in
      certain cases. However, the rapid increase in cesarean birth rates from 1996
      through 2011 without clear evidence of concomitant decreases in maternal or
      neonatal morbidity or mortality raises significant concern that cesarean delivery
      is overused. Variation in the rates of nulliparous, term, singleton, vertex
      cesarean births also indicates that clinical practice patterns affect the number
      of cesarean births performed. The most common indications for primary cesarean
      delivery include, in order of frequency, labor dystocia, abnormal or
      indeterminate (formerly, nonreassuring) fetal heart rate tracing, fetal
      malpresentation, multiple gestation, and suspected fetal macrosomia. Safe
      reduction of the rate of primary cesarean deliveries will require different
      approaches for each of these, as well as other, indications. For example, it may
      be necessary to revisit the definition of labor dystocia because recent data show
      that contemporary labor progresses at a rate substantially slower than what was
      historically taught. Additionally, improved and standardized fetal heart rate
      interpretation and management may have an effect. Increasing women's access to
      nonmedical interventions during labor, such as continuous labor and delivery
      support, also has been shown to reduce cesarean birth rates. External cephalic
      version for breech presentation and a trial of labor for women with twin
      gestations when the first twin is in cephalic presentation are other of several
      examples of interventions that can contribute to the safe lowering of the primary
      cesarean delivery rate. 

PMID- 24565432
TI  - The effect of a program to shorten the decision-to-delivery interval for emergent
      cesarean section on maternal and neonatal outcome.
AB  - OBJECTIVE: To study the effect of a departmental program designed to shorten the
      decision-to-delivery interval (DDI) for emergency cesarean section (ECS) for
      nonreassuring fetal heart rate (NRFHR) on maternal and neonatal outcome. STUDY
      DESIGN: A protocol for managing ECS that included documenting precise time
      intervals, identification of delaying obstacles and debriefing of each case, was
      implemented from March 2011. All women who delivered by ECS for NRFHR, as the
      only indication were included. Detailed information regarding DDI, maternal
      intraoperative and postoperative complications, and neonatal early outcomes were
      compared before (period-P1) (-27 months) and after (period 2) (+27 months)
      program implementation. RESULTS: During 54 months of study, 593 ECS DDI were
      included. Mean DDI decreased at period 2 (12.3 +/- 3.8 min, n = 301) compared
      with period 1 (21.7 +/- 9.1 min, n = 292), P < .001. Rate of cord pH <=7.1 and 5
      min Apgar score <=7 decreased at period 2 compared with period 1, P = .016 and P
      = .031, respectively. Worse composite neonatal outcome decreased at period 2
      compared with period 1, 15.6% vs 32.2%, respectively, P >= .001. Composite
      maternal outcome did not differ between the groups. Worse neonatal outcome was
      dependent on time period (period 1), odds ratio, 2.12; 95% confidence interval,
      1.27-3.55; P = .004 and on gestational age at delivery, odds ratio, 0.68; 95%
      confidence interval, 0.62-0.76; P < .001. CONCLUSION: Introduction of a
      management protocol to shorten DDI in ECS for NRFHR was associated with improved
      early neonatal outcome without change in maternal complications.

PMID- 24565431
TI  - Distinct cervical microRNA profiles are present in women destined to have a
      preterm birth.
AB  - OBJECTIVE: Although premature cervical remodeling is involved in preterm birth
      (PTB), the molecular pathways that are involved have not been elucidated fully.
      MicroRNAs (miRNAs) that are highly conserved single-stranded noncoding RNAs that
      play a crucial role in gene regulation have now been identified as important
      players in disease states. The objective of this study was to determine whether
      miRNA profiles in cervical cells are different in women who are destined to have
      a PTB compared with a term birth. STUDY DESIGN: A nested case-control study was
      performed. With the use of a noninvasive method, cervical cells were obtained at
      2 time points in pregnancy. The cervical cell miRNA expression profiles were
      compared between women who ultimately had a PTB (n = 10) compared with a term
      birth (n = 10). MiRNA expression profiles were created with the Affymetrix
      GeneChip miRNA Array. The data were analyzed with the Significance of Analysis of
      Microarrays and Principle Components Analyses. A false-discovery rate of 20% was
      used to determine the most differentially expressed miRNAs. Validation was
      performed with quantitative polymerase chain reaction. In vitro studies were
      performed to confirm expression and regulation of select miRNAs. RESULTS: With a
      false-discovery rate of 20% of the 5640 miRNAs that were analyzed on the array,
      99 miRNAs differed between those with a PTB vs a term birth. Qualitative
      polymerase chain reaction validated the array findings. In vitro studies
      confirmed expression of select miRNAs in cervical cells. CONCLUSION: MiRNA
      profiles in cervical cells may distinguish women who are at risk for PTB months
      before the outcome. With the large downstream effects of miRNAs on gene
      expression, these studies provide a new understanding of the processes that are
      involved in premature cervical remodeling and allow for the discovery of new
      therapeutic targets.

PMID- 24565433
TI  - Medicinal Extracts have a long tradition with human civilizations.

PMID- 24565434
TI  - [Pathogenesis of cataract after vitrectomy].
AB  - Cataract is the most common complication after vitrectomy. At first posterior
      subcapsular, it evolves into a nuclear type. A better understanding of the
      pathophysiologic mechanisms could help to develop strategies to prevent this
      complication. The main causative factors are oxidative stress, as evidenced by
      the persistence of an elevated partial pressure of oxygen in the lens after
      vitrectomy and the ionic changes in the lens. Mechanical factors may also be
      implicated: direct contact by gas tamponade or by silicone oil leads to
      desiccation cataract. The key of prevention of the formation of these cataracts
      is based on the reduction of oxidative stress. 

PMID- 24565435
TI  - [Scleritis as presenting sign of ciliary body melanoma].

PMID- 24565436
TI  - [Focal choroidal excavation: role of en-face OCT analysis and review of the
      literature].

PMID- 24565437
TI  - Functional approach to high-throughput plant growth analysis.
AB  - METHOD: Taking advantage of the current rapid development in imaging systems and
      computer vision algorithms, we present HPGA, a high-throughput phenotyping
      platform for plant growth modeling and functional analysis, which produces better
      understanding of energy distribution in regards of the balance between growth and
      defense. HPGA has two components, PAE (Plant Area Estimation) and GMA (Growth
      Modeling and Analysis). In PAE, by taking the complex leaf overlap problem into
      consideration, the area of every plant is measured from top-view images in four
      steps. Given the abundant measurements obtained with PAE, in the second module
      GMA, a nonlinear growth model is applied to generate growth curves, followed by
      functional data analysis. RESULTS: Experimental results on model plant
      Arabidopsis thaliana show that, compared to an existing approach, HPGA reduces
      the error rate of measuring plant area by half. The application of HPGA on the
      cfq mutant plants under fluctuating light reveals the correlation between low
      photosynthetic rates and small plant area (compared to wild type), which raises a
      hypothesis that knocking out cfq changes the sensitivity of the energy
      distribution under fluctuating light conditions to repress leaf growth.
      AVAILABILITY: HPGA is available at http://www.msu.edu/~jinchen/HPGA.

PMID- 24565438
TI  - Predicting beta-turns in proteins using support vector machines with fractional
      polynomials.
AB  - BACKGROUND: beta-turns are secondary structure type that have essential role in
      molecular recognition, protein folding, and stability. They are found to be the
      most common type of non-repetitive structures since 25% of amino acids in protein
      structures are situated on them. Their prediction is considered to be one of the
      crucial problems in bioinformatics and molecular biology, which can provide
      valuable insights and inputs for the fold recognition and drug design. RESULTS:
      We propose an approach that combines support vector machines (SVMs) and logistic
      regression (LR) in a hybrid prediction method, which we call (H-SVM-LR) to
      predict beta-turns in proteins. Fractional polynomials are used for LR modeling.
      We utilize position specific scoring matrices (PSSMs) and predicted secondary
      structure (PSS) as features. Our simulation studies show that H-SVM-LR achieves
      Qtotal of 82.87%, 82.84%, and 82.32% on the BT426, BT547, and BT823 datasets
      respectively. These values are the highest among other beta-turns prediction
      methods that are based on PSSMs and secondary structure information. H-SVM-LR
      also achieves favorable performance in predicting beta-turns as measured by the
      Matthew's correlation coefficient (MCC) on these datasets. Furthermore, H-SVM-LR
      shows good performance when considering shape strings as additional features.
      CONCLUSIONS: In this paper, we present a comprehensive approach for beta-turns
      prediction. Experiments show that our proposed approach achieves better
      performance compared to other competing prediction methods.

PMID- 24565439
TI  - A data-driven acute inflammation therapy.
AB  - Acute inflammation is a severe medical condition defined as an inflammatory
      response of the body to an infection. Its rapid progression requires quick and
      accurate decisions from clinicians. Inadequate and delayed decisions makes acute
      inflammation the 10th leading cause of death overall in United States with the
      estimated cost of treatment about $17 billion annually. However, despite the
      need, there are limited number of methods that could assist clinicians to
      determine optimal therapies for acute inflammation. We developed a data-driven
      method for suggesting optimal therapy by using machine learning model that is
      learned on historical patients' behaviors. To reduce both the risk of failure and
      the expense for clinical trials, our method is evaluated on a virtual patients
      generated by a mathematical model that emulates inflammatory response. In
      conducted experiments, acute inflammation was handled with two complimentary pro-
      and anti-inflammatory medications which adequate timing and doses are crucial for
      the successful outcome. Our experiments show that the dosage regimen assigned
      with our data-driven method significantly improves the percentage of healthy
      patients when compared to results by other methods used in clinical practice and
      found in literature. Our method saved 88% of patients that would otherwise die
      within a week, while the best method found in literature saved only 73% of
      patients. At the same time, our method used lower doses of medications than
      alternatives. In addition, our method achieved better results than alternatives
      when only incomplete or noisy measurements were available over time as well as it
      was less affected by therapy delay. The presented results provide strong evidence
      that models from the artificial intelligence community have a potential for
      development of personalized treatment strategies for acute inflammation. 

PMID- 24565440
TI  - Management of regional metastatic disease in head and neck cutaneous malignancy.
      2. Cutaneous malignant melanoma.
AB  - This is the second of 2 articles giving an overview of the current evidence for
      management of the neck and parotid in cutaneous cancers of the head and neck. We
      discuss cutaneous malignant melanoma and review the latest evidence for
      management of the regional nodes. 

PMID- 24565442
TI  - The impact of structural diversity and parameterization on maps of the protein
      universe.
AB  - BACKGROUND: Low dimensional maps of protein structure space (MPSS) provide a
      powerful global representation of all proteins. In such mappings structural
      relationships are depicted through spatial adjacency of points, each of which
      represents a molecule. MPSS can help in understanding the local and global
      topological characteristics of the structure space, as well as elucidate
      structure-function relationships within and between sets of proteins. A number of
      meta- and method-dependent parameters are involved in creating MPSS. However, at
      the state-of-the-art, a systematic investigation of the influence of these
      parameters on MPSS construction has yet to be carried out. Further, while
      specific cases in which MPSS out-perform pairwise distances for prediction of
      functional annotations have been noted, no general explanation for this
      phenomenon has yet been advanced. METHODS: We address the above questions within
      the technical context of creating MPSS by utilizing multidimensional scaling
      (MDS) for obtaining low-dimensional projections of structure alignment distances.
      RESULTS AND CONCLUSION: MDS is demonstrated as an effective method for
      construction of MPSS where related structures are co-located, even when their
      functional and evolutionary proximity cannot be deduced from distributions of
      pairwise comparisons alone. In particular, we show that MPSS exceed pairwise
      distance distributions in predictive capability for those annotations of shared
      function or origin which are characterized by a high level of structural
      diversity. We also determine the impact of the choice of structure alignment and
      MDS algorithms on the accuracy of such predictions.

PMID- 24565441
TI  - Intraclass correlation coefficients for cluster randomized trials in care
      pathways and usual care: hospital treatment for heart failure.
AB  - BACKGROUND: Cluster randomized trials are increasingly being used in healthcare
      evaluation to show the effectiveness of a specific intervention. Care pathways
      (CPs) are becoming a popular tool to improve the quality of health-care services
      provided to heart failure patients. In order to perform a well-designed cluster
      randomized trial to demonstrate the effectiveness of Usual care (UC) and CP in
      heart failure treatment, the intraclass correlation coefficient (ICC) should be
      available before conducting a trial to estimate the required sample size. This
      study reports ICCs for both demographical and outcome variables from cluster
      randomized trials of heart failure patients in UC and care pathways. METHODS: To
      calculate the degree of within-cluster dependence, the ICC and associated 95%
      confidence interval were calculated by a method based on analysis of variance.
      All analyses were performed in R software version 2.15.1. RESULTS: ICCs for
      baseline characteristics ranged from 0.025 to 0.058. The median value and
      interquartile range was 0.043 [0.026-0.052] for ICCs of baseline characteristics.
      Among baseline characteristics, the highest ICCs were found for admission by
      referral or admission from home (ICC = 0.058) and the disease severity at
      admission (ICC = 0.046). Corresponding ICCs for appropriateness of the stay,
      length of stay and hospitalization cost were 0.069, 0.063, and 0.001 in CP group
      and 0.203, 0.020, 0.046 for usual care, respectively. CONCLUSION: Reported values
      of ICCs from present care pathway trial and UC results for some common outcomes
      will be helpful for estimating sample size in future clustered randomized heart
      failure trials, in particular for the evaluation of care pathways.

PMID- 24565443
TI  - Arachidonic acid promotes migration and invasion through a PI3K/Akt-dependent
      pathway in MDA-MB-231 breast cancer cells.
AB  - Arachidonic acid (AA) is a common dietary n-6 cis polyunsaturated fatty acid that
      under physiological conditions is present in an esterified form in cell membrane
      phospholipids, however it might be present in the extracellular microenvironment.
      AA and its metabolites mediate FAK activation, adhesion and migration in MDA-MB
      231 breast cancer cells. However, it remains to be investigated whether AA
      promotes invasion and the signal transduction pathways involved in migration and
      invasion. Here, we demonstrate that AA induces Akt2 activation and invasion in
      MDA-MB-231 cells. Akt2 activation requires the activity of Src, EGFR, and PIK3,
      whereas migration and invasion require Akt, PI3K, EGFR and metalloproteinases
      activity. Moreover, AA also induces NFkappaB-DNA binding activity through a PI3K
      and Akt-dependent pathway. Our findings demonstrate, for the first time, that
      Akt/PI3K and EGFR pathways mediate migration and invasion induced by AA in MDA-MB
      231 breast cancer cells. 

PMID- 24565445
TI  - An integrated in vitro model of perfused tumor and cardiac tissue.
AB  - Cancer and cardiovascular disease remain the two leading causes of death in the
      United States. Progress in treatment to reduce morbidity and mortality will
      include the development of new drugs. Recent advances in induced pluripotent stem
      cell technology, tissue engineering, and microfabrication techniques have created
      a unique opportunity to develop three-dimensional (3D) microphysiological systems
      that more accurately reflect in vivo human biology when compared with two
      dimensional flat systems or animal models. Our group is working to develop 3D
      microphysiological systems using induced pluripotent stem cell technology that
      simulates the microcirculation, the cardiac muscle, and the solid tumor, and then
      to combine these systems into an integrated microphysiological system that
      simulates perfused cardiac muscle and solid tumor on a single platform. The
      platform will be initially validated to predict anti-cancer efficacy while
      minimizing cardiac muscle toxicity. A critical feature will be blood flow through
      a human microcirculation (capillaries and larger microvessels), which is
      necessary to overcome diffusion limitations of nutrients and waste products in
      realistic 3D cultures, and serves to integrate multiple organ systems. This is a
      necessary and critical feature of any platform that seeks to simulate integrated
      human organ systems. The results of our project should produce a new paradigm for
      efficient and accurate drug and toxicity screening, initially for anti-cancer
      drugs with minimal cardiac side effects, and a platform technology that can be
      eventually used to integrate multiple major organ systems of the human body. 

PMID- 24565444
TI  - A single mutation in the GSTe2 gene allows tracking of metabolically based
      insecticide resistance in a major malaria vector.
AB  - BACKGROUND: Metabolic resistance to insecticides is the biggest threat to the
      continued effectiveness of malaria vector control. However, its underlying
      molecular basis, crucial for successful resistance management, remains poorly
      characterized. RESULTS: Here, we demonstrate that the single amino acid change
      L119F in an upregulated glutathione S-transferase gene, GSTe2, confers high
      levels of metabolic resistance to DDT in the malaria vector Anopheles funestus.
      Genome-wide transcription analysis revealed that GSTe2 was the most over
      expressed detoxification gene in DDT and permethrin-resistant mosquitoes from
      Benin. Transgenic expression of GSTe2 in Drosophila melanogaster demonstrated
      that over-transcription of this gene alone confers DDT resistance and cross
      resistance to pyrethroids. Analysis of GSTe2 polymorphism established that the
      point mutation is tightly associated with metabolic resistance to DDT and its
      geographical distribution strongly correlates with DDT resistance patterns across
      Africa. Functional characterization of recombinant GSTe2 further supports the
      role of the L119F mutation, with the resistant allele being more efficient at
      metabolizing DDT than the susceptible one. Importantly, we also show that GSTe2
      directly metabolizes the pyrethroid permethrin. Structural analysis reveals that
      the mutation confers resistance by enlarging the GSTe2 DDT-binding cavity,
      leading to increased DDT access and metabolism. Furthermore, we show that GSTe2
      is under strong directional selection in resistant populations, and a restriction
      of gene flow is observed between African regions, enabling the prediction of the
      future spread of this resistance. CONCLUSIONS: This first DNA-based metabolic
      resistance marker in mosquitoes provides an essential tool to track the evolution
      of resistance and to design suitable resistance management strategies.

PMID- 24565446
TI  - Invasive fungal infections after natural disasters.
AB  - The link between natural disasters and subsequent fungal infections in disaster
      affected persons has been increasingly recognized. Fungal respiratory conditions
      associated with disasters include coccidioidomycosis, and fungi are among several
      organisms that can cause near-drowning pneumonia. Wound contamination with
      organic matter can lead to post-disaster skin and soft tissue fungal infections,
      notably mucormycosis. The role of climate change in the environmental growth,
      distribution, and dispersal mechanisms of pathogenic fungi is not fully
      understood; however, ongoing climate change could lead to increased disaster
      associated fungal infections. Fungal infections are an often-overlooked clinical
      and public health issue, and increased awareness by health care providers, public
      health professionals, and community members regarding disaster-associated fungal
      infections is needed. 

PMID- 24565447
TI  - Toll-like receptors in the depressed and suicide brain.
AB  - Abnormalities of the immune function in depression and suicide are based in part
      on the observation of increased levels of proinflammatory cytokines in the serum
      and postmortem brain of depressed and suicidal patients. We have examined if
      abnormalities of the innate immune receptors, known as Toll-like receptors
      (TLRs), in the brain are associated with depression and suicide, since the
      activation of these receptors results in production of cytokines. Of all the TLRs
      shown to be present in humans, TLR3 and TLR4 appear to be unique and important in
      brain function. We have determined the protein (by ELISA method) and mRNA
      expression (using qPCR) of TLR3 and TLR4 in the postmortem brain (dorsolateral
      prefrontal cortex [DLPFC]) of 22 depressed suicide victims, 11 non-depressed
      suicide victims, 12 depressed non-suicide subjects and 20 normal control
      subjects. We found that the mRNA expression of TLR3 and TLR4 was significantly
      increased in DLPFC of depressed suicide victims and in depressed non-suicide
      subjects, compared with controls. However, the protein expression of TLR3 and
      TLR4 was significantly increased in depressed suicide victims, but not in
      depressed non-suicide subjects compared with controls. The observed abnormalities
      of proinflammatory cytokines in the brain of suicide victims may be related to an
      abnormality of TLR3 and TLR4 over-expression. To our knowledge, this is the first
      study of TLRs in the brain of psychiatric subjects. 

PMID- 24565448
TI  - Anaplasma phagocytophilum antibodies in humans, Japan, 2010-2011.

PMID- 24565451
TI  - Asthma adherence management for the clinician.
AB  - BACKGROUND: Nonadherence to asthma treatment has been related to increased
      hospital and emergency care, morbidity, and unnecessary costs. Improving patient
      adherence is a key component to achieving optimal outcomes. OBJECTIVE: Review
      barriers, interventions, and communication skills shown to be effective in
      promoting asthma adherence. METHODS: Asthma adherence literature was reviewed.
      RESULTS: Sequential management principles to achieve adherence include the
      following: (1) measuring adherence, (2) identifying barriers that result in
      nonadherence, (3) using specific strategies to overcome barriers; and (4) using
      communication skills to enhance the delivery of selected strategies. CONCLUSION:
      Careful attention to adherence management principles may increase adherence,
      enhance outcomes, and reduce unnecessary morbidity and cost. The case described
      applies these principles and gives the reader a framework to review.

PMID- 24565452
TI  - When the chief complaint is (or should be) dyspnea in adults.
AB  - Dyspnea, "a subjective experience of breathing discomfort that consists of
      qualitatively distinct sensations that vary in intensity," is an important and
      challenging complaint associated with a wide variety of adverse clinical
      outcomes, including hospitalizations for chronic obstructive pulmonary disease
      and cardiac mortality. Although up to 85% of cases are caused by asthma, chronic
      obstructive pulmonary disease, interstitial lung disease, pneumonia, cardiac
      ischemia, congestive heart failure, or psychogenic disorders, a systematic
      approach can help to identity uncommon, but important, causes of dyspnea. In this
      review that includes clinical examples as well as a didactic review of currently
      available information, we suggest a step-wise approach to the evaluation of the
      adult patient with dyspnea. It is also important to avoid 3 possible pitfalls:
      accepting a cause for dyspnea in which the element identified is only part of a
      syndrome which includes that element; accepting a single cause for dyspnea when
      the cause is multifactorial; and failing to recognize a diagnosis and cause of
      dyspnea is incorrect and has been assumed without rigorous confirmation, when a
      patient with a specific diagnosis is referred for "failing to respond to
      treatment." 

PMID- 24565450
TI  - Severe asthma: an expanding and mounting clinical challenge.
AB  - Although all patients with asthma have variable airflow obstruction, airway
      inflammation, and bronchial hyperresponsiveness, some have disease that is severe
      in many aspects: persistent airflow obstruction, ongoing symptoms, increased
      frequency of exacerbations, and, most importantly, a diminished response to
      medications. A number of definitions have emerged to characterize the clinical
      features of severe asthma, but a central feature of this phenotype is the need
      for high doses of medications, especially corticosteroids, in attempts to achieve
      disease control. The prevalence of severe asthma is also undergoing reevaluation
      from the usual estimate of 10% to larger numbers on the basis of medication needs
      and the lack of disease control achieved. At present, the underlying mechanisms
      of severe asthma are not established but likely reflect a heterogeneous pattern,
      rather than a single unifying process. Guideline-directed treatment for severe
      asthma has limits with usual approaches centered on high doses of inhaled
      corticosteroids, long-acting beta-agonists, and trials with omalizumab, the
      monoclonal antibody to IgE. With the development of approaches to recognize
      asthma phenotypes with distinct pathogenesis and hence unique therapeutic
      targets, it is hoped that a personalized strategy in treatment directed toward
      disease-specific features will improve outcomes for this high-risk, severely
      affected population of patients. 

PMID- 24565453
TI  - Management of difficult-to-treat atopic dermatitis.
AB  - Atopic dermatitis is a complex disorder caused by the interplay between multiple
      genetic and environmental factors. Particularly in patients with severe disease,
      the effect is not just an itchy rash but also the secondary effects on the
      psychological well-being of the patient and their carers, particularly disturbed
      sleep. The aim of this review is to provide health care professionals with a
      holistic approach to the management of difficult-to-treat atopic dermatitis,
      defined as atopic dermatitis seemingly unresponsive to simple moisturizers and
      mild potency (classes VI and VII) topical corticosteroids. The critical
      importance of education and advice is emphasized, as is the seminal role of
      secondary bacterial infection and polyclonal T-cell activation in causing acute
      flares in patients with severe, generalized disease. In atypical cases or those
      that do not respond to treatment, alternative diagnoses should be considered. 

PMID- 24565454
TI  - Quality of life, health care utilization, and control in older adults with
      asthma.
AB  - BACKGROUND: Older adults with asthma have worse quality of life, asthma control
      and increased health care utilization than do healthy peers. Factors that
      contribute to this are currently unknown. OBJECTIVE: To identify demographic,
      psychological or physiologic characteristics associated with asthma quality of
      life, control and health care utilization in older adults. METHODS: By using a
      cross-sectional design, subjects older than 65 years with a history of physician
      diagnosed asthma were enrolled. Demographic, psychological and physiological
      characteristics (including spirometry, atopy testing and exhaled nitric oxide)
      were collected. Correlations between these factors and the mini Asthma Quality of
      Life Questionnaire, Asthma Control Questionnaire and health care utilization were
      assessed. RESULTS: Seventy subjects were enrolled in the study, with a mean age
      of 73.3 years and mean duration of asthma diagnosis of 28.5 years. Higher
      depression screening scores and self-reported depression were strongly correlated
      with poorer quality of life and asthma control after controlling for confounding
      effects through a regression model. In addition, worse overall functional status
      was correlated with poorer asthma quality of life (P < .01), presence of atopy
      was associated with decreased health care utilization (P < .01) and subjects who
      lived alone were more likely to have unscheduled visits to a physician's office
      (P = .06). CONCLUSIONS: Comorbid depression is strongly associated with poorer
      asthma quality of life and control in older adults. In addition, worse functional
      status and living alone may be associated with poorer outcomes. Screening for
      these conditions is important in the care of the elderly asthmatic population.

PMID- 24565455
TI  - Reassessment of omalizumab-dosing strategies and pharmacodynamics in inner-city
      children and adolescents.
AB  - BACKGROUND: Treatment regimens for omalizumab are guided by a dosing table that
      is based on total serum IgE and body weight. Limited data exist about onset and
      offset of omalizumab efficacy in children and adolescents or subgroups that most
      benefit from treatment. OBJECTIVES: Post hoc analyses were conducted to (1)
      examine patient characteristics of those eligible and ineligible for omalizumab,
      (2) describe onset of effect after initiation of omalizumab and offset of
      treatment effect after stopping therapy, and (3) determine whether the efficacy
      differs by age, asthma severity, dosing regimen, and prespecified biomarkers.
      METHODS: Inner-city children and adolescents with persistent allergic asthma were
      enrolled in the Inner-City Anti-IgE Therapy for Asthma trial that compared
      omalizumab with placebo added to guidelines-based therapy for 60 weeks. RESULTS:
      Two hundred ninety-three of 889 participants (33%) clinically suitable for
      omalizumab were ineligible for dosing according to a modified dosing table
      specifying IgE level and body weight criteria. Baseline symptoms were comparable
      among those eligible and ineligible to receive omalizumab, but other
      characteristics (rate of health care utilization and skin test results) differed.
      The time of onset of omalizumab effect was <30 days and time of offset was
      between 30 and 120 days. No difference in efficacy was noted by age or asthma
      severity, but high exhaled nitric oxide, blood eosinophils, and body mass index
      predicted efficacy. CONCLUSIONS: A significant portion of children and
      adolescents particularly suited for omalizumab because of asthma severity status
      may be ineligible due to IgE >1300 IU/mL. Omalizumab reduced asthma symptoms and
      exacerbations rapidly; features associated with efficacy can be identified to
      guide patient selection.

PMID- 24565457
TI  - Prospective evaluation of an anaphylaxis education mini-handout: the AAAAI
      Anaphylaxis Wallet Card.
AB  - BACKGROUND: Few anaphylaxis education materials have been prospectively evaluated
      in randomized controlled trials. OBJECTIVE: Our objective was to evaluate the
      American Academy of Allergy, Asthma & Immunology Anaphylaxis Wallet Card (AAAAI
      AWC) as an anaphylaxis education mini-handout for health care professionals.
      METHODS: We performed a randomized controlled study of the AAAAI-AWC with
      residents in general pediatrics at Miami Children's Hospital. Participants in the
      intervention group completed a pretest about anaphylaxis, heard a 3-minute
      PowerPoint presentation based on the AAAAI-AWC, reviewed the AAAAI-AWC, and
      discussed it with the presenter. After this, participants took a post-test
      immediately and a follow-up test 4 weeks later. Participants in the control group
      took the pretest, were handed an AAAAI-AWC, studied it briefly, then took the
      post-test immediately and the follow-up test 4 weeks later. RESULTS: Fifty-five
      residents participated. Regardless of the amount of time spent studying the AAAAI
      AWC, when the pretests were compared with the post-tests and follow-up tests,
      residents in both the intervention and control groups were more likely to
      recognize anaphylaxis symptoms (P < .05), name asthma as the most common comorbid
      disease in children with fatal or near-fatal anaphylaxis (P < .05), and recall
      the names of epinephrine auto injectors (P < .05) and the epinephrine doses
      available in these auto injectors (P < .05). When the pretests were compared with
      the post-tests and the follow-up tests, residents in the intervention group were
      more likely than controls to identify the body organ systems involved in severe
      or fatal anaphylaxis correctly (P < .05). CONCLUSION: The AAAAI-AWC is a
      practical, concise anaphylaxis education mini-handout for pediatric residents, a
      time-challenged group of health care professionals.

PMID- 24565458
TI  - International study of risk-mitigating factors and in-flight allergic reactions
      to peanut and tree nut.
AB  - BACKGROUND: Three studies have analyzed in-flight peanut/tree nut reactions,
      although the studies were conducted exclusively among Americans. OBJECTIVE: We
      studied the international in-flight experience and determined the efficacy of
      certain risk-mitigation strategies. METHODS: A 47-question on-line survey was
      distributed through the websites and social media outlets of the member
      organizations of the Food Allergy & Anaphylaxis Alliance. Both persons reporting
      an in-flight reaction and nonreactors were surveyed to assess details of air
      travel preparation and any reported reaction. Data were analyzed to determine the
      association among flying behaviors, reported reactions, and nationality. RESULTS:
      We found that 349 reactions were reported among 3273 respondents from 11
      countries; 13.3% received epinephrine as treatment. Flight crews were notified
      about 50.1% of reactions. Sixty-nine percent of all respondents reported making a
      preflight accommodation request, although just 55% of reactors did so compared
      with 71.6% of nonreactors (P < .001). Adjusted odds of epinephrine use were
      increased with reported gastrointestinal or cardiovascular symptoms or with
      notifying the crew. Passengers who requested any accommodation, requested a
      peanut/tree nut-free meal, wiped their tray table, avoided airline pillows or
      blankets, requested a buffer zone, requested other passengers not consume
      peanut/tree nut-containing products, or reported not consuming airline-provided
      food had significantly lower adjusted odds of reporting a reaction. CONCLUSIONS:
      In-flight peanut and tree nut reactions occur internationally. Epinephrine was
      sparsely used to treat reactions. We identified 8 risk-mitigating behaviors
      associated with lower odds of a reported reaction. Future study is necessary to
      further validate the effectiveness of these passenger-initiated risk-mitigating
      behaviors.

PMID- 24565459
TI  - Systemic contact dermatitis to ethanol.

PMID- 24565460
TI  - The basophil activation test identified carminic acid as an allergen inducing
      anaphylaxis.

PMID- 24565461
TI  - Cross-reactivity between royal jelly and Dermato-phagoides pteronyssinus.

PMID- 24565462
TI  - When to discontinue venom immunotherapy: the role of retesting to venom.

PMID- 24565466
TI  - Current drug development for antidepressants and ideas addressing downstream
      glutamate: the ketamine example.

PMID- 24565456
TI  - Biologic mechanisms of environmental tobacco smoke in children with poorly
      controlled asthma: results from a multicenter clinical trial.
AB  - BACKGROUND: Environmental tobacco smoke (ETS) negatively affects children with
      asthma. The prevalence of ETS exposure among children with poor asthma control
      may be changing. Importantly, the mechanisms by which ETS worsens asthma control
      are poorly understood. OBJECTIVE: We describe how ETS affects gastroesophageal
      reflux (GER), respiratory infections, and leukotriene production among children
      with poor asthma control. METHODS: We analyzed data from 306 children between 6
      and 17 years of age with poorly controlled asthma enrolled in a 6-month clinical
      trial. We evaluated prevalence and determinants of ETS exposure by interview,
      questionnaire, and urinary cotinine and the association of ETS exposure on
      leukotriene production, respiratory infections, GER, lung function, and asthma
      control. We used multivariable linear, logistic, and Poisson regressions to
      assess outcomes. RESULTS: ETS prevalence estimates ranged from 6% to 30%.
      Children with domestic indoor exposure had worse asthma control (c-Asthma Control
      Test, 17.8 vs 21.5; P = .04), worse FEV1 % predicted (84.1 vs 90.7; P = .02), and
      a trend for increased mean urinary leukotriene E4. ETS from any setting was
      associated with increased symptomatic respiratory infections (adjusted incidence
      rate ratio: 1.30; P = .02). However, children exposed to ETS did not have
      symptoms or pH probe results, suggestive of heightened GER. CONCLUSIONS: Domestic
      smoking exposure was associated with both higher rates of symptomatic respiratory
      infection and poorer asthma control despite generally intensive controller
      therapy. ETS exposure is common among asthmatic children with poor control and
      may worsen asthma control by promoting respiratory infections. Further
      investigation is required to elucidate ETS mechanisms in poor asthma control.

PMID- 24565465
TI  - Activity of 129 single-agent drugs in 228 phase I and II clinical trials in
      multiple myeloma.
AB  - BACKGROUND: More than 400 preclinical studies report >= 1 compound as cytotoxic
      to multiple myeloma (MM) cells; however, few of these agents became relevant in
      the clinic. Thus, the utility of such assays in predicting future clinical value
      is debatable. PATIENTS AND METHODS: We examined the application of early-phase
      trial experiences to predict future clinical adoption. We identified 129 drugs
      explored as single agents in 228 trials involving 7421 patients between 1961 and
      2013. RESULTS: All drugs in common use in MM (melphalan, dexamethasone,
      prednisone, cyclophosphamide, bendamustine, thalidomide, lenalidomide,
      pomalidomide, bortezomib, carfilzomib, and doxorubicin) demonstrated a best
      reported response rate of >= 22%. Older agents, including teniposide,
      fotemustine, paclitaxel, and interferon, also appear active by this criterion;
      however, if mean response rates from all reported trials for an agent are
      considered, then only drugs with a mean response rate of 15% partial response are
      in clinical use. CONCLUSION: Our analysis suggests that thresholds of 20% for
      best or 15% for mean response are highly predictive of future clinical success.
      Below these thresholds, no drug has yet reached regulatory approval or widespread
      use in the clinic. Thus, this benchmark provides 1 element of the framework for
      guiding choice of drugs for late-stage clinical testing.

PMID- 24565467
TI  - Alpine skiing injuries in Finland - a two-year retrospective study based on a
      questionnaire among Ski racers.
AB  - BACKGROUND: Alpine skiing is one of the most popular winter sports in the world.
      Nevertheless, it has always been associated with a high risk of injury. There are
      however, only a few studies that have examined the risk of injury of competitive
      skiers, especially of the junior ski racers. METHODS: The inclusion criterion was
      an injury in alpine skiing resulting in a pause in training longer than one week.
      Athletes of all ages were included. The study period was from the start of the
      season of 2008-2009 to end of the season of 2009-2010 (two years). RESULTS: The
      average annual number of ski racers in Finland was 661. There were 61 injuries
      (36 males with a median age of 14 years, 25 females with a median age of 14)
      fulfilling the inclusion criteria. Ligamentous knee injury was the most frequent
      (17) and lower leg fracture the second common (16) injury, respectively. There
      was a female dominance in the ACL injuries. Only one major abdominal injury and
      no major head injuries were observed. The overall training pause was 26 weeks
      after the ACL injury and 17 weeks after the lower leg fracture, respectively.
      CONCLUSION: The most common and most disabling injuries affect the knee and the
      lower leg. The high number of lower leg and ACL injuries is alarming. A
      continuous and careful monitoring of injuries needs to be established to assess
      this trend. A systematic review of injuries is the appropriate way to monitor the
      effects of changes made in terms of safety. The present retrospective two-year
      pilot study forms a base for a continuous alpine ski injury survey in Finland.

PMID- 24565470
TI  - Categorizing biomedicine images using novel image features and sparse coding
      representation.
AB  - BACKGROUND: Images embedded in biomedical publications carry rich information
      that often concisely summarize key hypotheses adopted, methods employed, or
      results obtained in a published study. Therefore, they offer valuable clues for
      understanding main content in a biomedical publication. Prior studies have
      pointed out the potential of mining images embedded in biomedical publications
      for automatically understanding and retrieving such images' associated source
      documents. Within the broad area of biomedical image processing, categorizing
      biomedical images is a fundamental step for building many advanced image
      analysis, retrieval, and mining applications. Similar to any automatic
      categorization effort, discriminative image features can provide the most crucial
      aid in the process. METHOD: We observe that many images embedded in biomedical
      publications carry versatile annotation text. Based on the locations of and the
      spatial relationships between these text elements in an image, we thus propose
      some novel image features for image categorization purpose, which quantitatively
      characterize the spatial positions and distributions of text elements inside a
      biomedical image. We further adopt a sparse coding representation (SCR) based
      technique to categorize images embedded in biomedical publications by leveraging
      our newly proposed image features. RESULTS: we randomly selected 990 images of
      the JPG format for use in our experiments where 310 images were used as training
      samples and the rest were used as the testing cases. We first segmented 310
      sample images following the our proposed procedure. This step produced a total of
      1035 sub-images. We then manually labeled all these sub-images according to the
      two-level hierarchical image taxonomy proposed by 1. Among our annotation
      results, 316 are microscopy images, 126 are gel electrophoresis images, 135 are
      line charts, 156 are bar charts, 52 are spot charts, 25 are tables, 70 are flow
      charts, and the remaining 155 images are of the type "others". A serial of
      experimental results are obtained. Firstly, each image categorizing results is
      presented, and next image categorizing performance indexes such as precision,
      recall, F-score, are all listed. Different features which include conventional
      image features and our proposed novel features indicate different categorizing
      performance, and the results are demonstrated. Thirdly, we conduct an accuracy
      comparison between support vector machine classification method and our proposed
      sparse representation classification method. At last, our proposed approach is
      compared with three peer classification method and experimental results verify
      our impressively improved performance. CONCLUSIONS: Compared with conventional
      image features that do not exploit characteristics regarding text positions and
      distributions inside images embedded in biomedical publications, our proposed
      image features coupled with the SR based representation model exhibit superior
      performance for classifying biomedical images as demonstrated in our comparative
      benchmark study.

PMID- 24565472
TI  - Glutathione S-transferase gene polymorphisms in celiac disease and their
      correlation with genomic instability phenotype.
AB  - BACKGROUND AND OBJECTIVE: Genomic instability and reduced glutathione S
      transferase (GST) activity have been identified as potential risk factors for
      malignant complications in celiac disease (CD). In this study, we assessed the
      possible influence of GST polymorphisms on genome instability phenotypes in a
      genetically characterised group of celiac patients from previous studies.
      METHODS: The deletion polymorphisms in GSTM1 and GSTT1 genes and the single
      nucleotide polymorphism GSTP1 c.313A>G were genotyped using PCR in a set of 20
      untreated adult patients with a known genomic instability phenotype and 69 age-
      and sex-matched healthy individuals. RESULTS: The frequencies of variant
      genotypes in patients were GSTM1-null (30%), GSTT1-null (5%), GSTP1-AG (60%) and
      GSTP1-GG (15%), and they showed no differences from controls. No significant
      differences were found in the genotype distribution based on telomere length.
      Cases with GSTM1-null genotype (83%) and microsatellite stability were more
      frequent than those with genomic instability. Moreover, carriers of GSTP1-variant
      genotype (73%) and stable phenotype were significantly increased compared to
      unstable patients (27%) (P=0.031). No differences were found according to the
      clinical-pathological characteristics of celiac cases. CONCLUSIONS: No
      association between GST polymorphic variants and celiac-associated genomic
      instability was proven in our cohort. Future studies should explore the
      usefulness of other biomarkers to distinguish celiac patients who are susceptible
      to cancer development.

PMID- 24565471
TI  - Reduced circulating sTWEAK levels are associated with metabolic syndrome in
      elderly individuals at high cardiovascular risk.
AB  - BACKGROUND: The circulating soluble TNF-like weak inducer of apoptosis (sTWEAK)
      is a cytokine that modulates inflammatory and atherogenic reactions related to
      cardiometabolic risk. We investigated the association between sTWEAK levels and
      metabolic syndrome (MetS) and its components in older subjects at high
      cardiovascular risk. METHODS: Cross-sectional analysis of 452 non-diabetic
      individuals (men and women aged 55-80 years) at high cardiovascular risk. MetS
      was defined by AHA/NHLBI and IDF criteria. Logistic regression analyses were used
      to estimate odds ratios (ORs) for MetS and its components by tertiles of serum
      sTWEAK concentrations measured by ELISA. RESULTS: sTWEAK concentrations were
      lower in subjects with MetS than in those without. In gender- and age-adjusted
      analyses, subjects in the lowest sTWEAK tertile had higher ORs for overall MetS
      [1.71 (95% CI, 1.07-2.72)] and its components abdominal obesity [2.01 (1.15
      3.52)], hyperglycemia [1.94 (1.20-3.11)], and hypertriglyceridemia [1.73 (1.05
      2.82)] than those in the upper tertile. These associations persisted after
      controlling for family history of diabetes and premature coronary heart disease,
      lifestyle, kidney function and other MetS components. sTWEAK concentrations
      decreased as the number of MetS components increased. Individuals in the lowest
      vs the upper sTWEAK tertile had an increased risk of disclosing greater number of
      MetS features. Adjusted ORs for individuals with 2 vs <=1, 3 vs <=1, and >=4 vs
      <= 1 MetS components were 2.60 (1.09-6.22), 2.83 (1.16-6.87) and 6.39 (2.42
      16.85), respectively. CONCLUSION: In older subjects at high cardiovascular risk,
      reduced sTWEAK levels are associated with MetS: abdominal obesity,
      hypertriglyceridemia and hyperglycemia are the main contributors to this
      association.

PMID- 24565473
TI  - New global midwifery initiatives and why 2014 should be a good year for women and
      newborns.

PMID- 24565469
TI  - Early-onset dementias: diagnostic and etiological considerations.
AB  - This paper summarizes the body of literature about early-onset dementia (EOD)
      that led to recommendations from the Fourth Canadian Consensus Conference on the
      Diagnosis and Treatment of Dementia. A broader differential diagnosis is required
      for EOD compared with late-onset dementia. Delays in diagnosis are common, and
      the social impact of EOD requires special care teams. The etiologies underlying
      EOD syndromes should take into account family history and comorbid diseases, such
      as cerebrovascular risk factors, that may influence the clinical presentation and
      age at onset. For example, although many EODs are more likely to have Mendelian
      genetic and/or metabolic causes, the presence of comorbidities may drive the
      individual at risk for late-onset dementia to manifest the symptoms at an earlier
      age, which contributes further to the observed heterogeneity and may confound
      diagnostic investigation. A personalized medicine approach to diagnosis should
      therefore be considered depending on the age at onset, clinical presentation, and
      comorbidities. Genetic counseling and testing as well as specialized biochemical
      screening are often required, especially in those under the age of 40 and in
      those with a family history of autosomal dominant or recessive disease. Novel
      treatments in the drug development pipeline for EOD, such as genetic forms of
      Alzheimer's disease, should target the specific pathogenic cascade implicated by
      the mutation or biochemical defect. 

PMID- 24565474
TI  - Clonal diversity, virulence-associated genes and antimicrobial resistance profile
      of Staphylococcus aureus isolates from nasal cavities and soft tissue infections
      in wild ruminants in Italian Alps.
AB  - Staphylococcus aureus is a commensal and a pathogenic bacterium that causes a
      wide variety of diseases in humans and animals with a high impact on public
      health and the livestock industry. S. aureus virulence pattern, antimicrobial
      resistance profile and host specialization are of great concern both in livestock
      and in companion animals. Concerning wild animals, S. aureus carriage and
      antimicrobial resistance profile has been recently investigated in free-ranging
      species both in aquatic and terrestrial environment. Here we report genotyping
      (spa typing, Multilocus Sequence Typing and SCCmec typing), virulence and
      antimicrobial resistance profile of four S. aureus isolated in Alpine chamois
      (Rupicapra r. rupicapra) and roe deer (Capreolus capreolus), euthanized due to
      walking impairment and signs of disorientation. S. aureus was isolated from nasal
      cavities in both wild ruminant species and in soft tissue infections in chamois.
      A marked S. aureus genetic heterogeneity was detected: spa type t1523, sequence
      type 45 (Clonal Complex 45), and spa type t1328, ST22 (CC22) from the nasal
      cavities and the liver of a chamois kid respectively, t1773, ST700 (CC130) from
      an adult chamois abscess, and a new sequence type, ST2712, belonging to CC97 from
      the roe deer nasal cavities. One of the main findings was the confirmation that
      the t1328, ST22 isolate, obtained from the liver of the chamois kid, was a
      methicillin-resistant S. aureus (MRSA) harbouring a SCCmec cassette type IV. The
      set of virulence marker and toxin genes investigated showed profiles
      characteristic of the S. aureus lineages detected, including those of the human
      adapted ST (CC) 22 and ST (CC) 45 isolates.

PMID- 24565475
TI  - High concentrations of myeloperoxidase in the equine uterus as an indicator of
      endometritis.
AB  - Intraluminal fluid and excessive abnormal hyperedema are regularly used for the
      diagnosis of endometritis in the mare, which is routinely confirmed by the
      presence of neutrophils on endometrial smears. Studies show a relation between
      neutrophils and myeloperoxidase (MPO), an enzyme contained in and released by
      neutrophils during degranulation or after cell lysis. This enzyme has been found
      in many fluids and tissues, and associated with different inflammatory
      pathologies in the horse. The aims of this study were to assess the presence and
      concentration of MPO in the equine uterus, and to investigate its relation with
      neutrophils, and other clinical signs of endometritis. Mares (n = 51) were
      evaluated for the presence of intraluminal fluid and excessive endometrial edema
      before breeding, and a small volume lavage and cytology samples were obtained.
      From 69 cycles, supernatant of the uterine flushes was analyzed with a specific
      equine MPO ELISA assay to measure MPO concentration. Cytology samples were used
      for the diagnosis of endometritis. Myeloperoxidase was present in the uterus of
      all estrus mares in highly variable concentrations. Myeloperoxidase
      concentrations were significantly (P < 0.05) higher in samples with positive
      cytologies and in the presence of intraluminal fluid. Occasionally, some samples
      with negative cytologies showed high MPO concentration, but the opposite was
      never observed. Cycles presenting hyperedema weren't associated with high
      concentration of MPO, intraluminal fluid, or positive cytology, making it a poor
      diagnostic tool of endometritis. 

PMID- 24565477
TI  - Chronic rhinosinusitis.
AB  - A 50-year-old woman with nonallergic rhinitis, asthma, and aspirin intolerance
      presented with worsening symptoms of nasal congestion, purulent drainage, and
      anosmia. Nasal polyps were visualized on anterior rhinoscopy, and there was
      evidence of chronic rhinosinusitis (CRS) on imaging studies during work-up for
      another medical condition. Over a 2-year period she had numerous bouts of acute
      exacerbations of CRS which required multiple courses of antibiotics; however, she
      was unwilling to undergo surgery to reduce polyp burden. She successfully
      underwent aspirin desensitization and experienced partial relief of symptoms with
      daily aspirin ingestion. Nasal obstruction is a common symptom that can result
      from multiple causes, including mucosal disorders (eg, allergic and nonallergic
      rhinitis, rhinosinusitis, sarcoid) and structural disorders (eg, nasal septal
      deviation, tumors, mucoceles). The various causes and work-up for nasal
      obstruction are discussed with emphasis placed on CRS, which is a prevalent
      disease characterized by inflammation of the nose and paranasal sinuses for a
      duration of >12 weeks. The different subtypes of CRS, including CRS with and
      without nasal polyps, allergic fungal rhinosinusitis, and aspirin-exacerbated
      respiratory disease, are discussed along with pathogenesis, diagnosis, and
      treatment options.

PMID- 24565476
TI  - Towards a three-dimensional microfluidic liver platform for predicting drug
      efficacy and toxicity in humans.
AB  - Although the process of drug development requires efficacy and toxicity testing
      in animals prior to human testing, animal models have limited ability to
      accurately predict human responses to xenobiotics and other insults. Societal
      pressures are also focusing on reduction of and, ultimately, replacement of
      animal testing. However, a variety of in vitro models, explored over the last
      decade, have not been powerful enough to replace animal models. New initiatives
      sponsored by several US federal agencies seek to address this problem by funding
      the development of physiologically relevant human organ models on microscopic
      chips. The eventual goal is to simulate a human-on-a-chip, by interconnecting the
      organ models, thereby replacing animal testing in drug discovery and development.
      As part of this initiative, we aim to build a three-dimensional human liver chip
      that mimics the acinus, the smallest functional unit of the liver, including its
      oxygen gradient. Our liver-on-a-chip platform will deliver a microfluidic three
      dimensional co-culture environment with stable synthetic and enzymatic function
      for at least 4 weeks. Sentinel cells that contain fluorescent biosensors will be
      integrated into the chip to provide multiplexed, real-time readouts of key liver
      functions and pathology. We are also developing a database to manage experimental
      data and harness external information to interpret the multimodal data and create
      a predictive platform. 

PMID- 24565478
TI  - Current and future directions in pediatric allergic rhinitis.
AB  - BACKGROUND: Allergic rhinitis (AR) is a common pediatric problem that
      significantly affects sleep, learning, performance, and quality of life. In
      addition, it is associated with significant comorbidities and complications.
      OBJECTIVE: The aim was to provide an update on the epidemiology, comorbidities,
      pathophysiology, current treatment, and future direction of pediatric AR.
      METHODS: Literature reviews in each of these areas were conducted, and the
      results were incorporated. RESULTS: The prevalence of AR is increasing in the
      pediatric population and is associated with significant morbidity, comorbidities,
      and complications. The mainstay of current treatment strategies includes allergen
      avoidance, pharmacotherapy, and allergen specific immunotherapy. CONCLUSIONS: In
      the future, diagnosis will be improved by microarrayed recombinant allergen
      testing and therapy will be expanded to include emerging treatments such as
      sublingual immunotherapy and combination products.

PMID- 24565479
TI  - Update on immune mechanisms associated with sublingual immunotherapy: practical
      implications for the clinician.
AB  - Sublingual immunotherapy (SLIT) is established as a safe and efficacious
      treatment for patients with type I respiratory allergies. The ability of SLIT to
      elicit antigen (allergen)-specific tolerance is linked to the peculiar biology of
      oral antigen-presenting cells. In the absence of danger signals, Langerhans
      cells, myeloid dendritic cells, and macrophages located in oral tissues, tonsils,
      and draining cervical lymph nodes are biased toward the induction of T(H)1 and IL
      10-producing CD4(+) regulatory T cells, thus supporting tolerance as opposed to
      inflammation. Sublingual administration does not lead to any detectable systemic
      exposure of intact allergens nor to IgE neosensitization. Oral tissues contain
      limited numbers of mast cells located in submucosal areas, thereby explaining the
      well-established safety profile of SLIT, with mostly local but rare systemic
      reactions. The induction of CD4(+) regulatory T cells and blocking anti
      inflammatory IgGs or IgAs are considered important for tolerance induction after
      SLIT. Specific molecular signatures associated with tolerogenic dendritic cells
      were recently reported during the onset of SLIT efficacy in the peripheral blood
      of patients exhibiting clinical benefit. Collectively, these observations confirm
      the induction of strong allergen-specific suppressive/tolerogenic immune
      responses during SLIT and pave the ground for the identification of biomarkers of
      efficacy. Practical implications of this emerging scientific knowledge are
      presented (1) to support the rational design of second-generation sublingual
      vaccines based on purified allergens, vector systems and/or adjuvants and (2) to
      help the clinician in decision making during his/her practice.

PMID- 24565480
TI  - Headache and facial pain: differential diagnosis and treatment.
AB  - Headaches affect 90% of the population sometime during their life. Most are
      benign and fleeting, some are serious and life-threatening, and others require
      ongoing medical consultation and treatment. A careful history and physical is
      necessary to establish a differential diagnosis and to guide the choice of
      testing to make an accurate diagnosis. The most common types of headaches are
      discussed in this review. They are divided into primary and secondary headache
      disorders as classified by the International Headache Society. Primary headache
      disorders include migraine without and with aura, cluster and tension-type
      headaches. Secondary headaches are those that occur as a result of some other
      disorder and include brain tumors, rhinosinusitis, diseases of intracranial and
      extracranial vasculature, and temporomandibular joint disease. 

PMID- 24565481
TI  - Treatment of patients with a history of penicillin allergy in a large tertiary
      care academic hospital.
AB  - BACKGROUND: Prescribing antibiotics to patients with a history of penicillin
      allergy is common in clinical practice. Opting for non-beta-lactam antibiotics
      has its inconveniences and is often unnecessary, because most of these patients
      are in fact not allergic. OBJECTIVE: This study aimed to determine how physicians
      in a large Canadian tertiary-care academic hospital without allergists on staff
      treat patients with a history of penicillin allergy. METHODS: A retrospective
      study was conducted during a 1-year period among all patients hospitalized in the
      intensive care unit, coronary care unit, and internal medicine wards. Files of
      patients with a record of penicillin allergy were reviewed to assess the need for
      antibiotics during their hospitalization and the decision-making process
      underlying the choice of antibiotic. The additional costs of alternative
      antibiotics were calculated. RESULTS: The files of 1738 patients admitted over a
      1-year period were hand reviewed. A history of penicillin allergy was found in
      172 patients (9.9%). The allergic reaction was described in only 30% of cases and
      left unmentioned in 20.7%. Beta-lactam antibiotics were used on 56 occasions
      despite a history of penicillin allergy. The use of alternative antibiotics in
      place of the beta-lactam standard of care carried an additional cost of $15,672
      Canadian. CONCLUSION: Alleged penicillin allergy is common among hospitalized
      patients and leads to substantial additional costs. Poor documentation of
      penicillin allergy likely reflects a lack of knowledge on this issue in the
      medical community, which impairs optimal treatment of these patients. Increased
      education on this matter is needed, and allergists on staff could be part of the
      solution.

PMID- 24565482
TI  - Safely diagnosing clinically significant penicillin allergy using only
      penicilloyl-poly-lysine, penicillin, and oral amoxicillin.
AB  - BACKGROUND: Penicillin skin testing is rarely used to undiagnose penicillin
      "allergy" in the United States, partially because of concern that commercially
      available materials are inadequate. OBJECTIVE: We determined whether skin testing
      with only commercially available penicilloyl-poly-lysine and penicillin followed
      by an oral amoxicillin challenge, if skin test-negative, can safely identify
      clinically significant penicillin allergy. METHODS: Five hundred sequential
      persons with positive history of penicillin "allergy" were evaluated by skin
      testing with penicilloyl-poly-lysine and penicillin between June 8, 2010, and
      March 29, 2012. All persons with negative skin tests were given an oral
      amoxicillin challenge and observed for 1 hour. RESULTS: Persons undergoing
      penicillin allergy testing were representative of all health plan members with
      penicillin allergy. Only 4 persons (0.8%; 95% CI, 0.32%-2.03%) had a positive
      skin test result. Only 4 persons (0.8%; 95% CI, 0.32%-2.03%) had an acute
      objective oral amoxicillin challenge reaction. Fifteen persons (3.0%; 95% CI,
      1.83%-4.98%) had subjective oral challenge reactions, either acute transient
      itching or dizziness. All were women and 11 (73.3%) had multiple drug intolerance
      syndrome. None had severe reactions or objective signs. These were not considered
      to be positive challenge reactions. Sixty-eight subjects (13.6%) who were
      negative on testing were exposed to 88 courses of penicillins during 90 days of
      follow-up. New reactions were reported after 4 courses (4.5%), 3 (75%) occurring
      in subjects with multiple drug intolerance syndrome. CONCLUSIONS: Penicillin skin
      testing, using only penicilloyl-poly-lysine and penicillin, followed by oral
      amoxicillin challenge, if negative, can safely identify clinically significant
      IgE-mediated penicillin allergy in patients who use health care in the United
      States at this time.

PMID- 24565483
TI  - The time for penicillin skin testing is here.

PMID- 24565484
TI  - Auvi-Q versus EpiPen: preferences of adults, caregivers, and children.
AB  - BACKGROUND: Auvi-Q is a novel epinephrine autoinjector (EAI) that provides audio
      and visual cues for patients at risk for life-threatening allergic reactions.
      OBJECTIVE: We tested the preference for Auvi-Q or EpiPen with regard to method of
      instruction, preference to carry, device size, and device shape. METHODS: This
      large, multicenter, simulated-use study evaluated whether adults (aged 18-65
      years), caregivers (parents/guardians aged 18-65 years of children aged 5-17
      years), and children (aged 11-17 years), with and without experience in using an
      EAI, had a preference for the current design of Auvi-Q or the current design of
      EpiPen. Participants were given a scenario that involved anaphylaxis and were
      instructed to simulate use of an EAI. They received and tested each device
      individually according to the randomization assignment. After testing both
      devices, they completed a survey to indicate their preference for Auvi-Q versus
      EpiPen. RESULTS: Among all 693 participants combined, Auvi-Q was preferred over
      EpiPen on all study end points (P < .001). For experienced and inexperienced
      participants in all 3 groups (adults, caregivers, and children), Auvi-Q was
      preferred over EpiPen for method of instruction, preference to carry, and device
      size (all P < .001). The preference for Auvi-Q device shape was not significant
      among experienced children (P = .10); however, it was significant for
      inexperienced children (P = .04) and highly significant for experienced and
      inexperienced adults and caregivers (P < .001). CONCLUSION: In this large
      multicenter, simulated-use study, Auvi-Q was preferred over EpiPen by experienced
      and inexperienced adults, caregivers, and children.

PMID- 24565485
TI  - Immediate allergic hypersensitivity to quinolones associates with neuromuscular
      blocking agent sensitization.
AB  - BACKGROUND: We identified a case of quinolone allergic hypersensitivity
      associated with quaternary ammonium (QA) sensitization, the allergic determinant
      of neuromuscular blocking agents (NMBAs). Concomitant sensitization to several
      chemically different drugs is rarely reported and raises the question of a
      nonfortuitous association. OBJECTIVE: We evaluated a potential association
      between quinolone immediate allergic hypersensitivity and NMBA sensitization.
      METHODS: QA-specific IgE detection was prospectively performed in 26 patients who
      presented an immediate hypersensitivity reaction to quinolones: 17 with a
      confirmed allergic hypersensitivity and 9 with allergic hypersensitivity not
      confirmed. We also included a control population of 88 outpatients without a
      history of quinolone or NMBA hypersensitivity. Patients with positive QA-specific
      IgE benefited from a NMBA allergologic workup. RESULTS: The prevalence of
      positive QA-specific IgE was significantly higher in patients with quinolone
      allergic hypersensitivity (9/17, 53%) compared with patients with allergic
      hypersensitivity not confirmed (1/9, 11%) than in controls (3/88, 3.4%). In the
      quinolone allergic population, ofloxacin elicited inhibition of the 4 positive QA
      specific IgE sera tested, in a dose-response manner. Among the 9 patients with
      positive QA-specific IgE, the QA sensitization (positivity of specific IgE) was
      confirmed by positive skin tests and/or basophil activation tests to at least 1
      NMBA in 5 of the 7 tested patients. CONCLUSION: We report here the first
      documentation of a high prevalence of QA sensitization in patients with quinolone
      allergic hypersensitivity. These results suggest a new way for NMBA
      sensitization. It thus seems appropriate to investigate NMBA sensitization when
      quinolone allergic hypersensitivity is diagnosed.

PMID- 24565486
TI  - Development and preliminary validation of the Adult Asthma Adherence
      QuestionnaireTM.
AB  - BACKGROUND: Asthma medication adherence is related to better asthma outcomes, but
      identification of suboptimal patient adherence behavior is not standardized in
      clinical settings. OBJECTIVE: [corrected] The purpose of this study was to
      develop a practical questionnaire that reflects nonadherence risk and identifies
      potential adherence barriers. METHODS: A questionnaire that included 20 potential
      adherence questions was completed by 420 adult patients with asthma who filled a
      prescription for an inhaled corticosteroid (ICS) and a short-acting beta agonist
      (SABA) in the previous 6 months. Questions without substantial floor or ceiling
      effects that were significantly related to self-reported low adherence or
      previous ICS canister dispensings were identified. Internal consistency
      reliability was tested by Cronbach alpha. Relationships of these questions to
      Asthma Control Test scores, future percent of days covered for ICS dispensings,
      and future asthma exacerbations and SABA dispensings were determined. RESULTS:
      Five final questions were identified: following "my medication plan," forgetting,
      not "needing" the medications, side effects, and cost. Low internal consistency
      reliability (<0.50) suggested items should not be summarized by a single score.
      All five questions were related to Asthma Control Test scores. Following the
      medication plan, forgetting, and not needing medication were significantly
      related to prospective percent of days covered. Side effects were related to
      subsequent SABA and oral corticosteroid dispensings, and cost was significantly
      related to oral corticosteroid dispensings. CONCLUSIONS: We identified five
      questions related to other measures of adherence and to asthma control that can
      be used clinically to identify patients at risk of nonadherence and the specific
      adherence barriers involved.

PMID- 24565487
TI  - Canadian allergists' and nonallergists' perception of epinephrine use and
      vaccination of persons with egg allergy.
AB  - BACKGROUND: Studies suggest knowledge gaps about epinephrine use and vaccination
      of persons with egg allergy. OBJECTIVE: We compared the perception of Canadian
      allergists and nonallergists on issues related to epinephrine use and vaccination
      of persons with egg allergy. METHODS: Canadian allergists, pediatricians, general
      practitioners/family physicians and emergency room physicians were recruited
      through medical associations and surveyed on these issues. Multivariate logistic
      regression models were used to identify determinants of specific responses.
      RESULTS: One-hundred fourteen allergists and 613 nonallergists participated. For
      most issues with accepted best practices, allergists were more likely to adhere
      to recommendations. Allergists versus nonallergists were more likely to recommend
      intramuscular epinephrine for anaphylaxis (odds ratio [OR] = 3.8; 95% CI, 1.43
      10.11). Older physicians (OR = 0.98; 95% CI, 0.97-0.99), Canadian-Paediatric
      Surveillance-Program participants (OR = 0.48; 95% CI, 0.24-0.96), family
      physicians (OR = 0.39; 95% CI, 0.16-0.96), and general practitioners (OR = 0.14;
      95% CI, 0.04-0.52) were less likely to recommend intramuscular use. However, in
      severe anaphylaxis, >25% of both groups would not give epinephrine for patients
      presenting with breathing difficulties or hypotension. Use of epinephrine for
      severe anaphylaxis was less likely in older physicians (OR = 0.97; 95% CI, 0.95
      0.99), female physicians (OR = 0.60; 95% CI, 0.39-0.89), and those practicing in
      Ontario (OR = 0.56; 95% CI, 0.36-0.86), Manitoba (OR = 0.42; 95% CI, 0.19-0.90),
      or Nova-Scotia (OR = 0.31; 95% CI, 0.12-0.78). Allergists (OR = 6.22; 95% CI,
      3.60-10.72) and physicians treating mainly children (OR = 3.41; 95% CI, 1.87
      6.25), or practicing in Quebec (OR = 1.68; 95% CI, 1.12-2.55) were more likely to
      recommend measles-mumps-rubella vaccination in a community facility. CONCLUSION:
      Knowledge gaps about mode and indications for epinephrine administration and
      vaccination policies need to be addressed in future education programs to ensure
      prompt epinephrine use and to avoid unnecessary restriction of vaccines.

PMID- 24565488
TI  - Aquagenic urticaria.

PMID- 24565489
TI  - Successful treatment of idiopathic angioedema with ecallantide.

PMID- 24565491
TI  - Gelatin-containing sweets can elicit anaphylaxis in a patient with sensitization
      to galactose-alpha-1,3-galactose.

PMID- 24565490
TI  - Seventeen-year-old girl hospitalized for localized swelling, pruritus,
      tenderness, and lymphatic streaking with eosinophilia.

PMID- 24565492
TI  - Nonrespiratory symptoms before loss of asthma control in children.

PMID- 24565493
TI  - Successful clarithromycin desensitization in a macrolide-sensitive pediatric
      patient.

PMID- 24565494
TI  - Caregivers' perspectives on timing the transfer of responsibilities for
      anaphylaxis recognition and treatment from adults to children and teenagers.

PMID- 24565495
TI  - Factors associated with decisions to step down asthma medications.

PMID- 24565497
TI  - Anaphylactic reaction to white-faced hornet sting and elevated baseline
      (asymptomatic) serum tryptase.

PMID- 24565500
TI  - MOABS: model based analysis of bisulfite sequencing data.
AB  - Bisulfite sequencing (BS-seq) is the gold standard for studying genome-wide DNA
      methylation. We developed MOABS to increase the speed, accuracy, statistical
      power and biological relevance of BS-seq data analysis. MOABS detects
      differential methylation with 10-fold coverage at single-CpG resolution based on
      a Beta-Binomial hierarchical model and is capable of processing two billion reads
      in 24 CPU hours. Here, using simulated and real BS-seq data, we demonstrate that
      MOABS outperforms other leading algorithms, such as Fisher's exact test and
      BSmooth. Furthermore, MOABS analysis can be easily extended to differential 5hmC
      analysis using RRBS and oxBS-seq. MOABS is available at
      http://code.google.com/p/moabs/. 

PMID- 24565501
TI  - Toxic plasma concentration of ropivacaine after a paravertebral block in a
      patient suffering from severe hypoalbuminemia.
AB  - A case of systemic ropivacaine toxicity from a continuous thoracic paravertebral
      block in an adult patient who received a lobectomy is presented. The catheter was
      placed by the surgeon. Eleven hours after the start of the infusion, the patient
      experienced an arrhythmia leading to death. The total venous plasma concentration
      of ropivacaine was high (3.2 MUg/mL). Furthermore, the patient had severe
      hypoalbuminemia (albumin 24 g/L), which resulted in the increase of the unbound
      ropivacaine plasma concentration that was responsible for the toxic side effects.

PMID- 24565503
TI  - A neural network approach to multi-biomarker panel discovery by high-throughput
      plasma proteomics profiling of breast cancer.
AB  - BACKGROUND: In the past several years, there has been increasing interest and
      enthusiasm in molecular biomarkers as tools for early detection of cancer. Liquid
      chromatography tandem mass spectrometry (LC/MS/MS) based plasma proteomics
      profiling technique is a promising technology platform to study candidate protein
      biomarkers for early detection of cancer. Factors such as inherent variability,
      protein detectability limitation, and peptide discovery biases among LC/MS/MS
      platforms have made the classification and prediction of proteomics profiles
      challenging. Developing proteomics data analysis methods to identify multi
      protein biomarker panels for breast cancer diagnosis based on neural networks
      provides hope for improving both the sensitivity and the specificity of candidate
      cancer biomarkers for early detection. RESULTS: In our previous method, we
      developed a Feed Forward Neural Network-based method to build the classifier for
      plasma samples of breast cancer and then applied the classifier to predict blind
      dataset of breast cancer. However, the optimal combination C* in our previous
      method was actually determined by applying the trained FFNN on the testing set
      with the combination. Therefore, in this paper, we applied a three way data split
      to the Feed Forward Neural Network for training, validation and testing based. We
      found that the prediction performance of the FFNN model based on the three way
      data split outperforms our previous method and the prediction performance is
      improved from (AUC = 0.8706, precision = 82.5%, accuracy = 82.5%, sensitivity =
      82.5%, specificity = 82.5% for the testing set) to (AUC = 0.895, precision =
      86.84%, accuracy = 85%, sensitivity = 82.5%, specificity = 87.5% for the testing
      set). CONCLUSIONS: Further pathway analysis showed that the top three five-marker
      panels are associated with complement and coagulation cascades, signaling,
      activation, and hemostasis, which are consistent with previous findings. We
      believe the new approach is a better solution for multi-biomarker panel discovery
      and it can be applied to other clinical proteomics.

PMID- 24565502
TI  - High-level relatedness among Mycobacterium abscessus subsp. massiliense strains
      from widely separated outbreaks.
AB  - Three recently sequenced strains isolated from patients during an outbreak of
      Mycobacterium abscessus subsp. massiliense infections at a cystic fibrosis center
      in the United States were compared with 6 strains from an outbreak at a cystic
      fibrosis center in the United Kingdom and worldwide strains. Strains from the 2
      cystic fibrosis outbreaks showed high-level relatedness with each other and major
      level relatedness with strains that caused soft tissue infections during an
      epidemic in Brazil. We identified unique single-nucleotide polymorphisms in
      cystic fibrosis and soft tissue outbreak strains, separate single-nucleotide
      polymorphisms only in cystic fibrosis outbreak strains, and unique genomic traits
      for each subset of isolates. Our findings highlight the necessity of identifying
      M. abscessus to the subspecies level and screening all cystic fibrosis isolates
      for relatedness to these outbreak strains. We propose 2 diagnostic strategies
      that use partial sequencing of rpoB and secA1 genes and a multilocus sequence
      typing protocol. 

PMID- 24565504
TI  - Ultrasound-guided placement of midline catheters in the surgical intensive care
      unit: a cost-effective proposal for timely central line removal.
AB  - BACKGROUND: The early removal of central intravenous (IV) catheters, as a means
      of reducing the incidence of central line-associated blood stream infections
      (CLABSI), remains a major health care initiative. However, attaining IV access in
      the surgical intensive care unit (SICU) can be quite difficult. We report the
      success of a novel, resident-driven program for the placement of ultrasound
      guided midline catheters in critically ill patients. MATERIALS AND METHODS: A
      prospective pilot study of 31 subjects admitted to the SICU from June to December
      2011 was performed. Intermediate-length (20 cm) midline catheters were placed by
      trained housestaff, under ultrasound guidance, into the basilic or cephalic
      veins. Procedural details including time to cannulation, complications, and costs
      were recorded. RESULTS: Successful placement was achieved in 96.8% (n = 30), with
      a mean follow-up of 9.8 +/- 5.6 (range 2-21) days. An average of 1.3 +/- 0.7
      (range 1-4) attempts with a median of 13.0 +/- 14.5 (range 0.5-68) minutes was
      required for successful venous cannulation. The most common site was the basilic
      vein (n = 23). Only minor complications were encountered; three catheters leaked
      at the insertion site and one patient developed phlebitis. No CLABSI occurred.
      The total procedure cost was $87 per catheter for the SICU team compared with
      $1500 per catheter when performed by an interventional radiologist. During the
      study period, a total of 283 central line days were avoided with an estimated
      cost savings of $13,614. CONCLUSIONS: Ultrasound-guided midline catheters placed
      by the housestaff are a cost-effective alternative for patients in the SICU with
      difficult IV access. Successful placement can help facilitate early central line
      removal and thus may reduce CLABSI rates.

PMID- 24565505
TI  - Loss of vagal tone aggravates systemic inflammation and cardiac impairment in
      endotoxemic rats.
AB  - BACKGROUND: During the course of sepsis, often myocardial depression with
      hemodynamic impairment occurs. Acetylcholine, the main transmitter of the
      parasympathetic Nervus vagus, has been shown to be of importance for the
      transmission of signals within the immune system and also for a variety of other
      functions throughout the organism. Hypothesizing a potential correlation between
      this dysfunction and hemodynamic impairment, we wanted to assess the impact of
      vagal stimulation on myocardial inflammation and function in a rat model of
      lipopolysaccharide (LPS)-induced septic shock. As the myocardial tissue is
      (sparsely) innervated by the N. vagus, there might be an important anti
      inflammatory effect in the heart, inhibiting proinflammatory gene expression in
      cardiomyocytes and improving cardiac function. MATERIALS AND METHODS: We
      performed stimulation of the right cervical branch of the N. vagus in
      vagotomized, endotoxemic (1 mg/kg body weight LPS, intravenously) rats.
      Hemodynamic parameters were assessed over time using a left ventricular pressure
      volume catheter. After the experiments, hearts and blood plasma were collected,
      and the expression of proinflammatory cytokines was measured using quantitative
      reverse transcription polymerase chain reaction and enzyme-linked immunosorbent
      assay. RESULTS: After vagotomy, the inflammatory response was aggravated,
      measurable by elevated cytokine levels in plasma and ventricular tissue. In
      concordance, cardiac impairment during septic shock was pronounced in these
      animals. To reverse both hemodynamic and immunologic effects of diminished vagal
      tone, even a brief stimulation of the N. vagus was enough during initial LPS
      infusion. CONCLUSIONS: Overall, the N. vagus might play a major role in
      maintaining hemodynamic stability and cardiac immune homeostasis during septic
      shock.

PMID- 24565506
TI  - Robotic versus laparoscopic total mesorectal excision for rectal cancer: a meta
      analysis.
AB  - BACKGROUND: Robotic surgery has been used successfully in many branches of
      surgery; but there is little evidence in the literature on its use in rectal
      cancer (RC). We conducted this meta-analysis that included randomized controlled
      trials and nonrandomized controlled trials of robotic total mesorectal excision
      (RTME) versus laparoscopic total mesorectal excision (LTME) to evaluate whether
      the safety and efficacy of RTME in patients with RC are equivalent to those of
      LTME. MATERIALS AND METHODS: Pubmed, Embase, Cochrane Library, Ovid, and Web of
      Science databases were searched. Studies clearly documenting a comparison of RTME
      with LTME for RC were selected. Operative and recovery outcomes, early
      postoperative morbidity, and oncological parameters were evaluated. RESULTS:
      Eight studies were identified that included 1229 patients in total, 554 (45.08%)
      in the RTME and 675 (54.92%) in the LTME. Meta-analysis suggested that the
      conversion rate to open surgery in RTME was significantly lower than in LTME (P =
      0.0004). There were no significant differences in operation time, estimated blood
      loss, recovery outcome, postoperative morbidity and mortality, length of hospital
      stay, and the oncological accuracy of resection and local recurrence between the
      two groups. The positive rate of circumferential resection margins (P = 0.04) and
      the incidence of erectile dysfunction (P = 0.002) were lower in RTME compared
      with LTME. CONCLUSIONS: RTME for RC is safe and feasible, and the short- and
      medium-term oncological and functional outcomes are equivalent or preferable to
      LTME. It may be an alternative treatment for RC. More multicenter randomized
      controlled trials investigating the long-term oncological and functional outcomes
      are required to determine the advantages of RTME over LTME in RC.

PMID- 24565509
TI  - Cyclospora spp. in drills, Bioko Island, Equatorial Guinea.

PMID- 24565507
TI  - GIPR expression in gastric and duodenal neuroendocrine tumors.
AB  - BACKGROUND: Compounds targeting somatostatin-receptor-type-2 (SSTR2) are useful
      for small bowel neuroendocrine tumor (SBNET) and pancreatic neuroendocrine tumor
      (PNET) imaging and treatment. We recently characterized expression of 13 cell
      surface receptor genes in SBNETs and PNETs, identifying three drug targets (GIPR,
      OXTR, and OPRK1). This study set out to characterize expression of this gene
      panel in the less common neuroendocrine tumors of the stomach and duodenum
      (gastric and duodenal neuroendocrine tumors [GDNETs]). METHODS: Primary tumors
      and adjacent normal tissue were collected at surgery, RNA was extracted, and
      expression of 13 target genes was determined by quantitative polymerase chain
      reaction. Expression was normalized to GAPDH and POLR2A internal control genes.
      Expression relative to normal tissue (ddCT) and absolute expression (dCT) were
      calculated. Wilcoxon tests compared median expression with false discovery rate
      correction for multiple comparisons. RESULTS: Gene expression was similar in two
      gastric and seven duodenal tumors, and these were analyzed together. Like SBNETs
      (n = 63) and PNETs (n = 51), GDNETs showed significant overexpression compared
      with normal tissue of BRS3, GIPR, GRM1, GPR113, OPRK1, and SSTR2 (P < 0.05 for
      all). Of these, SSTR2 had the highest absolute expression in GDNETs (median dCT
      4.0). Absolute expression of BRS3, GRM1, GPR113, and OPRK1 was significantly
      lower than SSTR2 in GDNETs (P < 0.05 for all), whereas expression of GIPR was
      similar to SSTR2 (median 4.3, P = 0.4). CONCLUSIONS: As in SBNETs and PNETs, GIPR
      shows absolute expression close to SSTR2 but has greater overexpression relative
      to normal tissue (21.1 versus 3.5-fold overexpression). We conclude that GIPR
      could provide an improved signal-to-noise ratio for imaging versus SSTR2 and
      represents a promising novel therapeutic target in GDNETs.

PMID- 24565508
TI  - Long-term diabetic response to gastric bypass.
AB  - BACKGROUND: As obesity and type II diabetes continue to rise, bariatric surgery
      offers a solution, but few long-term studies are available. The purpose of this
      study was to evaluate the long-term outcomes of diabetic patients after gastric
      bypass. MATERIALS AND METHODS: This was a retrospective cohort study of all
      diabetic patients undergoing gastric bypass at our institution, from 1998 to
      2012. Patients were compared by postoperative diabetic response to treatment
      (i.e., response = off oral medication/insulin versus refractory = on oral
      medication/insulin) and followed at 1-, 3-, 5-, and 10-y intervals. Continuous
      data were analyzed using Student t-test or Wilcoxon rank-sum test. Multivariable,
      Cox proportional hazard regression model was performed to compute diabetic cure
      ratios and 95% confidence intervals. RESULTS: A total of 2454 bariatric surgeries
      were performed at our institution during the time period. A total of 707 diabetic
      patients were selected by Current Procedural Terminology codes for gastric
      bypass. Mean follow-up was 2.1 y. Incidence of diabetic response was 56% (1 y),
      58% (3 y), 60% (5 y), and 44% (10 y). Postoperatively, responsive patients
      experienced greater percentage of total body weight loss (1 y [P < 0.0001], 3 y
      [P = 0.0087], and 5 y [P = 0.013]), and less hemoglobin A1c levels (1 y [P =
      0.035] and 3 y [P = 0.040]) at follow-up than refractory patients. Multivariable
      analysis revealed a significant, independent inverse trend in incidence of
      diabetic cure as both age and body mass index decreased (Ptrend = 0.0019 and
      <0.0001, respectively). In addition, degenerative joint disease was independently
      associated with responsive diabetes (cure ratio = 1.6 [95% confidence interval =
      1.1-2.2]). CONCLUSIONS: At follow-up, both groups in our study experienced
      substantial weight loss; however, a greater loss was observed among the response
      group. Further research is needed to evaluate methods for optimizing patient care
      preoperatively and improving patient follow-up.

PMID- 24565510
TI  - Correction: Efficiency of non-ionic surfactants - EDTA for treating TPH and heavy
      metals from contaminated soil.

PMID- 24565513
TI  - The impact of periventricular white matter lesions in patients with bipolar
      disorder type I - CORRIGENDUM.

PMID- 24565512
TI  - Warm ischemia time and postoperative complications after partial nephrectomy for
      renal cell carcinoma.
AB  - OBJECTIVE: To evaluate the correlations between PADUA and RENAL scores, WIT and
      postoperative complications in a cohort of patients who underwent elective open
      or minimally invasive nephron sparing surgery for renal cell carcinoma. MATERIAL
      AND METHODS: We analyzed 96 consecutive patients who underwent partial
      nephrectomy for renal cell carcinoma between 2004 and 2013 at our Institution.
      The Spearman test was used to compare categorical variables. For all statistical
      analyses, a two-sided P < .05 was considered statistically significant. RESULTS:
      The median (IQR) PADUA score was 7 (7-8) and the median (IQR) RENAL score was 7
      (6-8). The median (IQR) warm ischemia time was 14 min (8-20). Low grade and high
      grade postoperative complications were found in 27 (28.1%) and 6 (6.3%) patients,
      respectively. PADUA risk group categories significantly correlated with WIT > 20
      minutes and high grade postoperative complications, respectively (P = .04),
      regardless of the surgical approach. RENAL risk group categories significantly
      predicted longer hilar clamping time in our cohort (P = .04), but no
      statistically significant correlations with high grade postoperative
      complications were found. CONCLUSIONS: In our retrospective series nephrometric
      scores demonstrated to significantly predict longer warm ischemia time and higher
      postoperative complications, especially in those patients with more challenging
      and complex renal tumors. Therefore, when planning to perform partial
      nephrectomy, urologists should widely use these comprehensive tools.

PMID- 24565515
TI  - Introduction to principal components analysis.

PMID- 24565511
TI  - Identification of a BET family bromodomain/casein kinase II/TAF-containing
      complex as a regulator of mitotic condensin function.
AB  - Condensin is a central regulator of mitotic genome structure with mutants showing
      poorly condensed chromosomes and profound segregation defects. Here, we identify
      NCT, a complex comprising the Nrc1 BET-family tandem bromodomain protein
      (SPAC631.02), casein kinase II (CKII), and several TAFs, as a regulator of
      condensin function. We show that NCT and condensin bind similar genomic regions
      but only briefly colocalize during the periods of chromosome condensation and
      decondensation. This pattern of NCT binding at the core centromere, the region of
      maximal condensin enrichment, tracks the abundance of acetylated histone H4, as
      regulated by the Hat1-Mis16 acetyltransferase complex and recognized by the first
      Nrc1 bromodomain. Strikingly, mutants in NCT or Hat1-Mis16 restore the formation
      of segregation-competent chromosomes in cells containing defective condensin.
      These results are consistent with a model where NCT targets CKII to chromatin in
      a cell-cycle-directed manner in order to modulate the activity of condensin
      during chromosome condensation and decondensation.

PMID- 24565514
TI  - Fluid biomarkers for diagnosing dementia: rationale and the Canadian Consensus on
      Diagnosis and Treatment of Dementia recommendations for Canadian physicians.
AB  - Fluid biomarkers improve the diagnostic accuracy in dementia and provide an
      objective measure potentially useful as a therapeutic response in clinical
      trials. The role of fluid biomarkers in patient care is a rapidly evolving field.
      Here, we provide a review and recommendations regarding the use of fluid
      biomarkers in clinical practice as discussed at the Fourth Canadian Consensus
      Conference on the Diagnosis and Treatment of Dementia (CCCDTD4) convened in
      Montreal, 4 to 5 May 2012. At present, there is no consensus regarding the
      optimal methodology for conducting quantification of plasma amyloid-beta (Abeta)
      peptides. In addition, since there is insufficient evidence supporting clinical
      applications for plasma Abeta-peptide measures, the CCCDTD4 does not recommended
      plasma biomarkers either for primary care or for specialists. Evidence for CSF
      Abeta1-42, total tau and phosphorylated tau in the diagnosis of Alzheimer
      pathology is much stronger, and can be considered at the tertiary care level for
      selected cases to improve diagnostic certainty, particularly in those cases
      presenting atypical clinical features. 

PMID- 24565516
TI  - Spanish-Latin American multicenter study of attitudes toward organ donation among
      personnel from hospital healthcare centers.
AB  - INTRODUCTION: Hospital personnel are a group which has an influence on the
      opinion of the rest of the population about healthcare matters. Any unfavorable
      attitude of this group would be an obstacle to an increase in organ donation.
      OBJECTIVE: To analyze the attitude of hospital workers toward the donation of
      one's own organs in Spanish and Latin American hospitals and to determine the
      factors affecting this attitude. MATERIAL AND METHOD: Eleven hospitals from the
      "International Collaborative Donor Project" were selected, 3 in Spain, 5 in
      Mexico, 2 in Cuba and one in Costa Rica. A random sample was stratified by the
      type of service and job category. Attitude toward donation and transplantation
      was assessed using a validated survey. The questionnaire was completed
      anonymously and was self-administered. STATISTICAL ANALYSIS: Student's t-test,
      the chi2 test and logistic regression analysis. RESULTS: Of the 2,785 workers
      surveyed, 822 were from Spain, 1,595 from Mexico, 202 from Cuba and 166 from
      Costa Rica and 79% (n=2,191) were in favor of deceased organ donation. According
      to country, 94% (n=189) of Cubans were in favor, compared to 82% (n=1,313) of the
      Mexicans, 73% (n=121) of the Costa Ricans and 69% (n=568) of the Spanish
      (P<.001). In the multivariate analysis, the following variables had the most
      specific weight: 1) originating from Cuba (odds ratio=8.196; P<.001); 2) being a
      physician (OR= 2.544; P<.001); 3) performing a job related to transplantation (OR
      = 1.610; P=.005); 4) having discussed the subject of donation and transplantation
      within the family (OR= 3.690; P<.001); 5) having a partner with a favorable
      attitude toward donation and transplantation (OR= 3.289; P<.001); 6) a
      respondent's belief that his or her religion is in favor of donation and
      transplantation (OR= 3.021; P=.001); 7) not being concerned about the possible
      mutilation of the body after donation (OR= 2.994; P<.001); 8) the preference for
      other options apart from burial for treating the body after death (OR= 2.770;
      P<.001); and 9) acceptance of carrying out an autopsy if one were needed (OR=
      2.808; P<.001). CONCLUSIONS: Hospital personnel in Spanish and Latin American
      healthcare centers had a favorable attitude toward donation, although 21% of
      respondents were not in favor of donating. This attitude was more favorable among
      Latin American workers and was very much conditioned by job-related and
      psychosocial factors.

PMID- 24565517
TI  - Microvesicle-mediated delivery of transforming growth factor beta1 siRNA for the
      suppression of tumor growth in mice.
AB  - Cell-derived microvesicles (MVs) have been recently shown as an efficient carrier
      to deliver small RNAs into the target cells. In the present study, we
      characterized the inhibitory effect of TGF-beta1 siRNA delivered by mouse
      fibroblast L929 cell-derived MVs (L929 MVs) on the growth and metastasis of
      murine sarcomas 180 cells both in vitro and in vivo. We found that, comparing to
      the same concentration of free TGF-beta1 siRNA, TGF-beta1 siRNA delivered by L929
      MVs much more efficiently decreased the level of TGF-beta1 in the recipient tumor
      cells. Functionally, MVs containing TGF-beta1 siRNA significantly decreased the
      viability and migration of sarcomas 180 cells and promoted the apoptosis of tumor
      cells. Co-immunoprecipitation with Argonaute 2 (AGO2) via anti-AGO2 antibody
      indicated that the majority of TGF-beta1 siRNA in the MVs were associated with
      AGO2 complex. A tumor implantation mouse model further showed that intravenous
      injection of TGF-beta1 siRNA-containing MVs strongly suppressed TGF-beta1
      expression and TGF-beta1 signaling downstream in the implanted tumor cells, and
      thus inhibited the growth and lung metastases of tumor cells. In conclusion, our
      results collectively demonstrate that the delivery of therapeutic TGF-beta1 siRNA
      by cell-derived MVs provides an effective strategy to control tumor cell growth
      and metastasis. 

PMID- 24565519
TI  - PEGylated liposomes with NGR ligand and heat-activable cell-penetrating peptide
      doxorubicin conjugate for tumor-specific therapy.
AB  - Cell-penetrating peptides (CPPs) mediated tumor-oriented nanocarriers have been
      widely studied by researchers recently. However, applications of CPPs in vivo
      were usually hampered by their loss in untargeted tissues and enzymatic
      degradation. These shortfalls required strategies to camouflage CPPs before their
      arrival at the targeted site. In this work, we constructed a thermosensitive
      liposome (TSL) containing Asparagines-Glycine-Arginine (NGR) peptide as the
      targeting moiety and heat-activable cell-penetrating peptide-doxorubicin
      conjugate for enhancing specific cancer therapy. Different to the masking
      strategies of CPPs reported, CPPs existing in conjugation form of CPPs and
      doxorubicin (CPP-Dox) were hidden in TSL to cloak and protect CPPs. Meanwhile,
      NGR moiety and local tumor hyperthermia were utilized to achieve specific
      targeting of CPPs to the tumor. The nanocarrier (CPP-Dox/NGR-TSL) prepared in
      this work possessed suitable physiochemical properties such as small particle
      size of about 90 nm, high drug encapsulation efficiency of approximately 95%,
      good stability in the medium containing 10% fetal bovine serum (FBS) and so on.
      In vitro experiments on Human fibrosarcoma cells (HT-1080) and human breast
      adenocarcinoma cells (MCF-7) verified the specific targeting ability and enhanced
      intracellular drug delivery of the liposomes to HT-1080 cells. Furthermore,
      comparing with NGR-targeted TSL containing Dox (Dox/NGR-TSL), the results of
      intravenous administration showed CPP-Dox/NGR-TSL significantly inhibited tumor
      growth in nude mice xenografted HT-1080 tumors and excellent body safety. In
      conclusion, the nanocarrier constructed in this study would be a safe and
      efficiently drug delivery system for specific cancer treatment. 

PMID- 24565518
TI  - Modulation of matrix elasticity with PEG hydrogels to study melanoma drug
      responsiveness.
AB  - Metastatic melanoma is highly resistant to drug treatment, and the underlying
      mechanisms of this resistance remain unclear. Increased tissue stiffness is
      correlated with tumor progression, but whether increased tissue stiffness
      contributes to treatment resistance in melanoma is not known. To investigate the
      effect of substrate stiffness on melanoma cell treatment responsiveness, PEG
      hydrogels were utilized as a cell culture system to precisely vary matrix
      elasticity and investigate melanoma cell responses to a commercially available
      pharmacological inhibitor (PLX4032). The tensile moduli were varied between 0.6
      and 13.1 kPa (E) and the effects of PLX4032 on metabolic activity, apoptosis, and
      proliferation were evaluated on human cell lines derived from radial growth phase
      (WM35) and metastatic melanoma (A375). The A375 cells were found to be stiffness
      independent; matrix elasticity did not alter cell morphology or apoptosis with
      PLX4032 treatment. The WM35 cells, however, were more dependent on substrate
      modulus, displaying increased apoptosis and smaller focal adhesions on compliant
      substrates. Culturing melanoma cells on PEG hydrogels revealed stage-dependent
      responses to PLX4032 that would have otherwise been masked if cultured strictly
      on TCPS. These findings demonstrate the utility of PEG hydrogels as a versatile
      in vitro culture platform with which to investigate the molecular mechanisms of
      melanoma biology and treatment responsiveness. 

PMID- 24565520
TI  - iNGR-modified PEG-PLGA nanoparticles that recognize tumor vasculature and
      penetrate gliomas.
AB  - A major cross-cutting problem for glioma therapy is the poor extravasation and
      penetration of the payload drug in target glioma parenchyma. Here, to overcome
      these obstacles, a tumor vessel recognizing and tumor penetrating system is
      developed by functionalizating the poly (ethyleneglycol)-poly (L-lactic-co
      glycolic acid) nanoparticles with an iNGR moiety (iNGR-NP). The nanoparticulate
      formulation is expected to achieve specific deep penetration in the tumor tissue
      by initially binding to aminopeptidase N, with iNGR proteolytically cleaved to
      CRNGR, and then bind with neuropilin-1 to mediate deep penetration in the tumor
      parenchyma. iNGR-NP exhibits significantly enhanced cellular uptake in human
      umbilical vein endothelial cells, improves the anti-proliferation and anti-tube
      formation abilities of paclitaxel in vitro. Following intravenous administration,
      iNGR-NP present favorable pharmacokinetic and tumor homing profiles. Glioma
      distribution and penetration assays confirm that iNGR-NP achieve the highest
      accumulation and deepest penetration at the glioma sites. The anti-glioma
      efficacy of paclitaxel-loaded iNGR-NP is verified by its improved anti
      angiogenesis activity and the significantly prolonged survival time in mice
      bearing intracranial glioma. These evidences highlight the potential of iNGR
      decorated nanoparticles in overcoming the leading edge problem in anti-glioma
      drug delivery.

PMID- 24565521
TI  - Purification of human adipose-derived stem cells from fat tissues using PLGA/silk
      screen hybrid membranes.
AB  - The purification of human adipose-derived stem cells (hADSCs) from human adipose
      tissue cells (stromal vascular fraction) was investigated using membrane
      filtration through poly(lactide-co-glycolic acid)/silk screen hybrid membranes.
      Membrane filtration methods are attractive in regenerative medicine because they
      reduce the time required to purify hADSCs (i.e., less than 30 min) compared with
      conventional culture methods, which require 5-12 days. hADSCs expressing the
      mesenchymal stem cell markers CD44, CD73, and CD90 were concentrated in the
      permeation solution from the hybrid membranes. Expression of the surface markers
      CD44, CD73, and CD99 on the cells in the permeation solution from the hybrid
      membranes, which were obtained using 18 mL of feed solution containing 50 * 104
      cells, was statistically significantly higher than that of the primary adipose
      tissue cells, indicating that the hADSCs can be purified in the permeation
      solution by the membrane filtration method. Cells expressing the stem cell
      associated marker CD34 could be successfully isolated in the permeation solution,
      whereas CD34+ cells could not be purified by the conventional culture method. The
      hADSCs in the permeation solution demonstrated a superior capacity for osteogenic
      differentiation based on their alkali phosphatase activity, their osterix gene
      expression, and the results of mineralization analysis by Alizarin Red S and von
      Kossa staining compared with the cells from the suspension of human adipose
      tissue. These results suggest that the hADSCs capable of osteogenic
      differentiation preferentially permeate through the hybrid membranes.

PMID- 24565522
TI  - Cisplatin-alginate conjugate liposomes for targeted delivery to EGFR-positive
      ovarian cancer cells.
AB  - Systemic side effects and low aqueous solubility have limited the clinical use of
      cisplatin (CDDP) in ovarian carcinoma and have contributed to failures in
      developing effective drug delivery systems. In order to develop a novel drug
      delivery system with enhanced efficacy and minimal adverse effects, we exploited
      the properties of sodium alginate (SA) to synthesize CDDP-SA conjugate (CS),
      which is highly soluble and readily incorporated into liposomes (CS-PEG-Lip).
      Epidermal growth factor receptor (EGFR) is overexpressed in many ovarian cancers,
      therefore we modified EGF on the liposomes (CS-EGF-Lip) to specifically target
      EGFR-expressing tumors, thereby increasing the bioavailability and efficacy of
      CDDP. In vitro experiments confirmed that EGF-Lip selectively recognized EGFR
      positive SKOV3 cells and effectively penetrated tumor spheroids. We demonstrated
      that CS-EGF-Lip possessed satisfactory size distribution and exhibited
      significantly improved encapsulation and loading efficiency. Furthermore, CS-EGF
      Lip sustained release of CDDP in vitro, suggesting that CS-EGF-Lip may retain the
      antitumor activity of CDDP. Inhibition of proliferation and migration was also
      greater with CS-EGF-Lip compared to CDDP. In vivo xenograft experiments revealed
      that administration of CS-EGF-Lip enhanced delivery of CDDP into ovarian tumor
      tissues and improved the antitumor efficacy of CDDP, while reducing
      nephrotoxicity and body weight loss in mice. These results suggest that CS-EGF
      Lip may offer a promising strategy for CDDP delivery in the treatment of EGFR
      positive ovarian carcinoma or similar tumors, with enhanced efficacy and fewer
      adverse effects. 

PMID- 24565523
TI  - Spinal cord organotypic slice cultures for the study of regenerating motor axon
      interactions with 3D scaffolds.
AB  - Numerous in-vitro techniques exist for investigating the influence of 3D
      substrate topography on sensory axon growth. However, simple and cost-effective
      methods for studying post-natal motor axon interactions with such substrates are
      lacking. Here, spinal cord organotypic slice cultures (OSC) from post-natal day 7
      9 rat pups were presented with spinal nerve roots, or blocks of fibrin hydrogel
      or 3D microporous collagen scaffolds to investigate motor axon-substrate
      interactions. By 7-14 days, axons from motor neuronal pools extended into the
      explanted nerve roots, growing along Schwann cell processes and demonstrating a
      full range of axon-Schwann cell interactions, from simple ensheathment to
      concentric wrapping by Schwann cell processes and the formation of compact myelin
      within a basal lamina sheath. Extensive motor axon regeneration and all stages of
      axon-Schwann interactions were also supported within the longitudinally
      orientated microporous framework of the 3D collagen scaffold. In stark contrast,
      the simple fibrin hydrogel only supported axon growth and cell migration over its
      surface. The relative ease of demonstrating such motor axon regeneration through
      the microporous 3D framework by immunofluorescence, two-photon microscopy and
      transmission electron microscopy strongly supports the adoption of this technique
      for assaying the influence of substrate topography and functionalization in
      regenerative bioengineering. 

PMID- 24565524
TI  - Antibacterial effects and biocompatibility of titanium surfaces with graded
      silver incorporation in titania nanotubes.
AB  - Most commercial dental implants are made of titanium (Ti) because Ti possesses
      excellent properties such as osseointegration. However, many types of Ti products
      still suffer from insufficient antibacterial capability and bacterial infection
      after surgery remains one of the most common and intractable complications. In
      this study, a dual process encompassing anodization and silver plasma immersion
      ion implantation (Ag PIII) is utilized to produce titania nanotubes (TiO2-NTs)
      containing Ag at different sites and depths. The concentration and depth of the
      incorporated Ag can be tailored readily by changing the PIII parameters. The Ag
      embedded TiO2-NTs which retain the nanotubular morphology are capable of
      sterilizing oral pathogens as opposed to pure Ti plates and pristine TiO2-NTs.
      Biological assays indicate that the in vitro and in vivo biocompatibility of the
      sample plasma-implanted at a lower voltage of 0.5 kV (NT-Ag-0.5) is significantly
      compromised due to the large amount of surface Ag. On the other hand, the sample
      implanted at 1 kV (NT-Ag-1.0) exhibits unimpaired effects due to the smaller
      surface Ag accumulation. Sample NT-Ag-1.0 is further demonstrated to possess
      sustained antibacterial properties due to the large embedded depth of Ag and the
      technique and resulting materials have large potential in dental implants.

PMID- 24565525
TI  - Hyaluronic acid-chitosan nanoparticles for co-delivery of MiR-34a and doxorubicin
      in therapy against triple negative breast cancer.
AB  - Metastatic relapse, development of drug resistance in cancer cells and adverse
      side effects of chemotherapeutic agents are the major obstacles for effective
      chemotherapy against triple-negative breast cancer. To address these problems,
      miR-34a, a potent endogenous tumor suppressive molecule in breast cancer, was co
      encapsulated with doxorubicin (DOX) into hyaluronic acid (HA)-chitosan (CS)
      nanoparticles (NPs) and simultaneously delivered into breast cancer cells for
      improved therapeutic effects of drug. DOX-miR-34a co-loaded HA-CS NPs were
      successfully prepared through ionotropic gelation method in water. In vitro and
      in vivo experiments showed that miR-34a and DOX can be efficiently encapsulated
      into HA-CS NPs and delivered into tumor cells or tumor tissues and enhance anti
      tumor effects of DOX by suppressing the expression of non-pump resistance and
      anti-apoptosis proto-oncogene Bcl-2. In addition, intracellular restoration of
      miR-34a inhibited breast cancer cell migration via targeting Notch-1 signaling.
      The obtained data suggest that co-delivery of DOX and miR-34a could achieve
      synergistic effects on tumor suppression and nanosystem-based co-delivery of
      tumor suppressive miRNAs and chemotherapeutic agents may be a promising combined
      therapeutic strategy for enhanced anti-tumor therapy. 

PMID- 24565527
TI  - Inferring protein domains associated with drug side effects based on drug-target
      interaction network.
AB  - BACKGROUND: Most phenotypic effects of drugs are involved in the interactions
      between drugs and their target proteins, however, our knowledge about the
      molecular mechanism of the drug-target interactions is very limited. One of
      challenging issues in recent pharmaceutical science is to identify the underlying
      molecular features which govern drug-target interactions. RESULTS: In this paper,
      we make a systematic analysis of the correlation between drug side effects and
      protein domains, which we call "pharmacogenomic features," based on the drug
      target interaction network. We detect drug side effects and protein domains that
      appear jointly in known drug-target interactions, which is made possible by using
      classifiers with sparse models. It is shown that the inferred pharmacogenomic
      features can be used for predicting potential drug-target interactions. We also
      discuss advantages and limitations of the pharmacogenomic features, compared with
      the chemogenomic features that are the associations between drug chemical
      substructures and protein domains. CONCLUSION: The inferred side effect-domain
      association network is expected to be useful for estimating common drug side
      effects for different protein families and characteristic drug side effects for
      specific protein domains.

PMID- 24565528
TI  - Timing and predictors for urinary drainage in children with expectantly managed
      grade IV renal trauma.
AB  - PURPOSE: We determined which children sustaining blunt grade IV renal trauma are
      at greatest risk for failing nonoperative management and in what time frame they
      will likely present. MATERIALS AND METHODS: We retrospectively reviewed children
      presenting with nonvascular grade IV blunt renal trauma between 2003 and 2012. We
      compared characteristics on computerized tomography, reasons for intervention,
      type and timing of surgery, length of hospital stay and need for readmission
      between children undergoing early intervention (less than 72 hours after
      admission) and those managed conservatively (with any subsequent intervention
      undertaken more than 72 hours after admission). RESULTS: A total of 26 children
      were identified with nonvascular grade IV blunt renal trauma. Conservative
      management was attempted in 16 cases (62%). Seven of these patients (44%)
      required intervention (ureteral stent and/or percutaneous drain placement), with
      a mean time to intervention of 11 days. Collecting system clot and larger urinoma
      (1.45 cm in cases with successful and 4.29 cm in those with failed conservative
      management) significantly predicted failure of conservative management (p<0.05).
      Presence of dissociated renal fragments (57% vs 11%) and interpolar contrast
      extravasation (57% vs 0%) were increased in the early intervention group compared
      to the conservatively managed group (p>0.05), as was rehospitalization (43% vs
      0%), mean length of stay (7.9 vs 5.4 days) and transfusion (14% vs 0%, p>0.05).
      CONCLUSIONS: Collecting system hematoma and urinoma size significantly predicted
      failure of conservative management, with a mean time to intervention of 11 days.
      Children with failed conservative management had a greater incidence of
      dissociated renal fragments and interpolar extravasation. Early identification of
      these patients may decrease hospital readmissions, length of stay and prolonged
      morbidity.

PMID- 24565526
TI  - The role of spacer carbon chain in acidic functional monomers on the
      physicochemical properties of self-etch dental adhesives.
AB  - OBJECTIVES: To evaluate the effects of acidic functional monomers with different
      hydrophilicity and spacer carbon chain length on the degree of conversion (DC),
      wettability (contact angle), water sorption (WS) and ultimate tensile strength
      (UTS) of experimental one-step self-etch adhesives (1-SEAs). METHODS: A series of
      standard resin blends was prepared with each formulation containing 15mol% of
      each acidic monomer. The structural variations of the acidic monomers were MEP
      (spacer chain with 2 carbons), MDP (10-carbons), MDDP (12-carbons), MTEP (more
      hydrophilic polyether spacer) and CAP-P (intermediate hydrophilicity ester
      spacer). Dumbbell-shaped and disc specimens were prepared and tested for UTS and
      WS, respectively. DC was assessed by FTIR, while the wettability of each 1-SEA
      was evaluated on glass slides and flat dentine surfaces. Results were analysed
      with one-way ANOVA and Tukey's test (p<0.05). RESULTS: The outcomes showed lower
      UTS for CAP-P, control blend and MEP than MTEP, MDDP and MDP (p<0.05). The degree
      of conversion was statistically similar for all resins (p=0.122). On dentine, the
      wettability was higher (lower contact angle) with the most hydrophilic monomer
      MTEP. Higher WS was attained using MTEP. Different lengths of the spacer chains
      did not result in different wettability and WS (p>0.05). CONCLUSION: At similar
      molar percentage, different acidic functional monomers induced similar degree of
      conversion and different UTS when included in a 1-SEA. However, the inclusion of
      highly hydrophilic monomer may increase the wettability on dentine and the WS.

PMID- 24565529
TI  - Bilateral differences in gait mechanics following total ankle replacement: a two
      year longitudinal study.
AB  - BACKGROUND: Following total ankle replacement (TAR) patients demonstrate
      improvements in gait. The purpose of this study was to assess the changes in gait
      symmetry from a pre-operative assessment through two years following TAR.
      METHODS: Seventy-eight patients who received a primary TAR and had no
      contralateral pain were examined. Three-dimensional joint mechanics and ground
      reaction forces were collected during seven walking trials pre-operatively, and 1
      and 2-years post-operatively. Data was analyzed using a 2*3 repeated measures
      ANOVA to determine significant differences between limbs and across time points
      (alpha=0.05). FINDINGS: Walking speed improved from pre-operative to each post
      operative time point (P<.001; ES=1.5). Peak dorsiflexion was not changed across
      time or between sides, however, the dorsiflexion angle at heel strike was
      increased on the nonsurgical side (P=0.049; ES=0.32). Peak plantar flexion moment
      (P<.001; ES=.80), stance (P<.001; ES=.29) and step time (P<.001; ES=.41) were
      improved from pre-op to 1year post-surgery on the surgical side. Step (P<.001;
      ES=1.2) and stride length (P<.001; ES=1.2) demonstrated improvements across all
      time points, while the weight acceptance (P<.001; ES=.27) and propulsion ground
      reaction forces (P<.001; ES=.22) showed improvements between pre-op and 1year
      post-op. INTERPRETATION: The results of the study indicate that the patients are
      able to walk faster and demonstrate an improvement in gait symmetry; however,
      this improvement does not return the patient to a symmetric walking pattern by
      2years post-TAR.

PMID- 24565530
TI  - Etiological mechanisms of isolated pontine infarcts based on arterial territory
      involvement.
AB  - BACKGROUND: Pontine infarcts can be classified into four regions based on the
      vascular anatomy: anteromedial, anterolateral, lateral and posterior. The purpose
      of this study was to determine if different etiological mechanisms are
      responsible for these four types of pontine infarcts. METHODS: We studied
      consecutive patients within 7 days of symptom onset who had isolated pontine
      infarcts on diffusion-weighted imaging. The factors associated with infarct
      topography were determined by multivariate logistic regression analysis. RESULTS:
      A total of 205 patients were enrolled (78 women; mean age, 72 +/- 11 years). The
      distribution of the infarcts was anteromedial in 73%, anterolateral in 14%,
      lateral in 3% and posterior in 10%. In multivariate logistic regression analysis,
      major cardioembolic sources (odds ratio (OR), 4.17; 95% confidence interval (CI),
      1.21-14.1) and previous ischemic stroke (OR, 2.92; 95% CI, 1.09-7.89) were
      positively associated with lateral or posterior infarcts compared with
      anteromedial infarcts. In contrast, advanced age (OR, 0.55; 95% Cl, 0.35-0.81 per
      10-year increase), diabetes mellitus (OR, 0.31; 95% CI, 0.11-0.80) and basilar
      artery disease (OR, 0.27; 95% CI, 0.08-0.75) were negatively associated with
      lateral or posterior pontine infarcts. CONCLUSIONS: Baseline characteristics were
      significantly different among patients with isolated pontine infarcts in
      different topographic locations. Our results suggest that cardioembolism is
      relatively common in lateral or posterior pontine infarcts, whereas basilar
      artery atherosclerosis is more common in anteromedial infarcts.

PMID- 24565531
TI  - Potential release of in vivo trace metals from metallic medical implants in the
      human body: from ions to nanoparticles--a systematic analytical review.
AB  - Metal ion release from metallic materials, e.g. metallic alloys and pure metals,
      implanted into the human body in dental and orthopedic surgery is becoming a
      major cause for concern. This review briefly provides an overview of both
      metallic alloys and pure metals used in implant materials in dental and
      orthopedic surgery. Additionally, a short section is dedicated to important
      biomaterials and their corrosive behavior in both real solutions and various
      types of media that model human biological fluids and tissues. The present review
      gives an overview of analytical methods, techniques and different approaches
      applied to the measurement of in vivo trace metals released into body fluids and
      tissues from patients carrying metal-on-metal prostheses and metal dental
      implants. Reference levels of ion concentrations in body fluids and tissues that
      have been determined by a host of studies are compiled, reviewed and presented in
      this paper. Finally, a collection of published clinical data on in vivo released
      trace metals from metallic medical implants is included.

PMID- 24565532
TI  - The real-world prevalence of Takotsubo syndrome in patients with ST-elevation
      myocardial infarction: highly underestimated.

PMID- 24565533
TI  - Comparison of prognostic impact of absolute lymphocyte count, absolute monocyte
      count, absolute lymphocyte count/absolute monocyte count prognostic score and
      ratio in patients with diffuse large B cell lymphoma.
AB  - BACKGROUND: The combination of absolute lymphocyte count (ALC) and absolute
      monocyte count (AMC) at diagnosis has prognostic relevance in patients with
      diffuse large B cell lymphoma (DLBCL). AIMS: The present study was designed to
      investigate the prognostic significance of ALC and AMC and to determine whether
      ALC/AMC ratio or ALC/AMC prognostic score is better predictor of outcome in
      DLBCL. METHODS: We retrospectively analyzed the prognostic significance of ALC
      and AMC, ALC/AMC ratio and ALC/AMC prognostic score at diagnosis in 222 DLBCL
      patients treated with R-CHOP. RESULTS: ROC analysis showed that optimal cut-off
      values of AMC and ALC/AMC ratio with the best sensitivity and specificity were
      0.59*10(9)/L and 2.8, respectively. Cut-off of ALC was determined according to
      the literature data (1*10(9)/L). Low ALC, high AMC, low ALC/AMC ratio and high
      ALC/AMC prognostic score were in significant association with lower rate of
      therapy response and survival. In contrast, these parameters were not in
      significant correlation with relapse rate. The patients with low ALC, "high" AMC,
      low ALC/AMC ratio and high ALC/AMC prognostic score at diagnosis had
      significantly shorter EFS and OS. In multivariate analysis all tested parameters
      (ALC, AMC, ALC/AMC prognostic score and ALC/AMC ratio) are independent risk
      factors along with "bulky" disease and IPI. CONCLUSION: All tested parameters
      (ALC, AMC, ALC/AMC score and ALC/AMC ratio) may be useful prognostic factors in
      DLBCL patients. ALC/AMC score has a slight advantage as it allows the
      classification of patients into three prognostic groups. Further studies are
      needed to determine which of these parameters has the highest predictive value.

PMID- 24565534
TI  - Gastric adenomas in familial adenomatous polyposis are common, but subtle, and
      have a benign course.
AB  - BACKGROUND: Patients with familial adenomatous polyposis (FAP) are known to have
      an increased risk for gastric adenomas. The clinical features of gastric adenomas
      in FAP have not been well characterized, and there is a lack of standardized
      approaches to the management of these lesions. AIMS: To study the endoscopic
      appearance, risk factors, clinical course, and response to therapy of gastric
      adenomas in patients with FAP. METHODS: We retrospectively reviewed the records
      of 97 patients with FAP who underwent esophagogastroduodenoscopy (EGD) at Mayo
      Clinic (Florida, Rochester and Arizona) between 2004 and 2013. RESULTS: Nine
      patients (9%) had biopsy-proven gastric adenomas. Adenomas were located in the
      antrum (five patients), in the body and fundus in the setting of background
      fundic gland polyps (FGP) (three patients), and in the body not associated with
      FGP (one patient). Adenoma size was 3-40 mm and the number of adenomas per
      patient ranged from one to 20. Adenomas in the antrum were flat and subtle,
      whereas those in the gastric body or fundus were polypoid and difficult to
      differentiate from the cystic FGPs seen in patients with FAP. The performing
      endoscopists reported difficulty with identifying adenomas, and six patients had
      at least one EGD within the previous three years where gastric adenomas were not
      reported. Adenomas were classified as tubular in eight patients and tubulovillous
      in one patient. High grade dysplasia was noted in one patient. After a median
      follow-up of 63 months (interquartile range: 20-149 months), no patient in our
      entire cohort (with or without gastric adenomas) developed gastric cancer. The
      patients in whom gastric adenoma developed, compared to those without gastric
      adenoma, were more likely to be younger [36 +/- 12 vs. 48 +/- 15 years, p =
      0.02], have concomitant chronic gastritis [22% vs. 0%, p = 0.008], and have
      desmoid tumors [5 (56%) vs. 19 (22%), p = 0.04]. CONCLUSIONS: Gastric adenomas
      are not uncommon in patients with FAP and are often difficult to identify
      endoscopically. Endoscopists should have a high degree of suspicion for gastric
      adenomas in these patients and a low threshold to biopsy. Given the benign
      clinical course, recommended initial management is conservative with endoscopic
      therapy and periodic surveillance.

PMID- 24565535
TI  - Studies on decolorization of reactive blue 19 textile dye by Coprinus plicatilis.
AB  - BACKGROUND: Studies were carried on the decolorization of the textile dye
      reactive blue 19 (RB 19) by a novel isolate of Coprinus plicatilis (C.
      plicatilis) fungi. We describe an in vitro optimization process for
      decolorization and its behavior under different conditions of carbon and nitrogen
      sources, pH, temperature and substrate concentration. RESULTS: The optimal
      conditions for decolorization were obtained in media containing intermediate
      concentrations of ammonium oxalate and glucose (10 g/L) as nitrogen and carbon
      sources, respectively, at 26 degrees C and pH = 5.5. Maximum decolorization
      efficiency against RB 19 achieved in this study was around 99%. Ultra-violet and
      visible (UV-vis) spectrophotometric analyses, before and after decolorization,
      suggest that decolorization was due to biodegradation. CONCLUSIONS: This effect
      was associated with laccase enzyme displaying good tolerance to a wide range of
      pH values, salt concentrations and temperatures, suggesting a potential role for
      this organism in the remediation of real dye containing effluents. In conclusion,
      laccase activity in C. plicatilis was firstly described in this study.

PMID- 24565536
TI  - Food protein-induced enterocolitis syndrome (FPIES): current management
      strategies and review of the literature.
AB  - Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated
      gastrointestinal food hypersensitivity that manifests as profuse, repetitive
      vomiting, often with diarrhea, leading to acute dehydration and lethargy or
      weight loss and failure to thrive if chronic. FPIES is elicited most commonly by
      milk and soy proteins; however, rice, oat, and other solid foods may also elicit
      FPIES. Certain FPIES features overlap with food protein-induced enteropathy and
      proctocolitis, whereas others overlap with anaphylaxis. FPIES is not well
      recognized among pediatricians and emergency department physicians; the affected
      children are often mismanaged as having acute viral gastrointestinal illness,
      sepsis, or surgical disease, delaying diagnosis of FPIES for many months. The aim
      of this review is to provide case-driven presentation of the features of FPIES.
      Although randomized clinical trials on management options are missing, the
      relevant current literature and authors' experience are reviewed in detail. 

PMID- 24565537
TI  - Guidance for the nutrition management of gastrointestinal allergy in pediatrics.
AB  - Food allergies and their related elimination diets have been associated with an
      increased risk of inadequate nutrient intake and poor growth in the pediatric
      population. In recognition of these nutritional risks, the National Institute of
      Allergy and Infectious Diseases Guidelines for the Diagnosis and Management of
      Food Allergy in the United States recommend nutrition counseling and close growth
      monitoring for all children with food allergy. The care of children with
      gastrointestinal food allergic disorders can be complicated and is best performed
      with a structured approach in which medical and nutrition needs are addressed
      simultaneously. Children with gastrointestinal food allergy may be at greater
      nutritional risk because of decreased dietary intake. For these children, it is
      important to perform a comprehensive nutrition assessment to identify nutrition
      related problems and to develop and implement a plan that meets the patient's
      needs within the context of the elimination diet. We provide an overview of the
      nutritional risks and strategies to assess nutritional status in pediatric
      patients with gastrointestinal food allergy. 

PMID- 24565538
TI  - The management of eosinophilic esophagitis.
AB  - Eosinophilic esophagitis (EoE) is a clinicopathologic, chronic esophageal
      inflammatory disease resistant to acid suppressive therapy and is associated with
      variable symptoms indicative of upper gastrointestinal dysfunction. Per current
      guidelines established by The International Group of Eosinophil Researchers
      (TIGERS), the diagnosis is made in symptomatic patients after a biopsy that
      confirms a peak eosinophil level of >=15 eosinophils/high-powered field (HPF).
      The esophagus is distinguished by pronounced tissue eosinophilia in which dietary
      antigens are key inciting factors for disease pathogenesis; EoE being reversed by
      elimination of triggering food allergens suggests that the disease is mediated in
      part by allergic sensitization to foods. Moreover, experimental EoE in mice can
      be induced not only via food exposure but also via aeroallergen exposure.
      Consistent with an allergic etiology rather than an acid-induced esophagitis,
      swallowed glucocorticoids are effective for the treatment of EoE. Evaluation by
      an allergist is a recommended part of the diagnostic workup, especially for
      management of allergic comorbidities. Clinical practice for the evaluation of
      patients with EoE mainly relies on prick skin tests due to the ease and
      validation of these tests in the context of immediate hypersensitivity. However,
      both atopy patch testing and serum IgE testing have been used in EoE. Herein, we
      reviewed the basic clinical features of EoE with a focus on the approach to
      diagnosing causative food allergens and to dietary therapy. 

PMID- 24565539
TI  - Food protein-induced enterocolitis syndrome: insights from review of a large
      referral population.
AB  - BACKGROUND: Food protein-induced enterocolitis (FPIES) is a rare non-IgE mediated
      disease. Most studies have been limited in nature, with the largest cohort being
      66 patients. The most common foods that have been reported are milk and soy.
      OBJECTIVE: A retrospective chart review of patients seen in the Allergy Section
      at The Children's Hospital of Philadelphia with International Classification of
      Diseases Ninth Revision code of 558.3 (Allergic Gastroenteritis and Colitis)
      between 2007 and 2012 was conducted to identify patients with suspected FPIES.
      Diagnosis of FPIES was confirmed based on meeting clinical criteria of delayed
      reaction with pronounced vomiting and/or diarrhea. Data regarding patient
      characteristics and features of their reactions were collected for analysis and
      comparison with existing studies. RESULTS: A total of 462 cases were identified
      in our chart review. Patients had a similar demographic profile to the normal
      allergy patients seen in our clinic. The most common foods identified were milk
      (67%), soy (41%), rice (19%), oat (16%), and egg (11%). Patients had onset of
      FPIES to milk and soy around 7 months of age compared with 12 months of age for
      solid foods. FPIES reactions were identified to meats, tree nuts, peanuts,
      fruits, and vegetables; 70% of the patients reacted to one or two foods. Skin
      prick testing and atopy patch testing were not helpful in identifying the foods.
      CONCLUSION: FPIES reactions were seen more frequently than previously described.
      However, the presentation and clinical features were similar to previous reports.
      Milk- and soy-triggered FPIES were common, and 43.5% of patients who had a milk
      trigger reacted to soy. There is no laboratory test to identify foods that cause
      FPIES, and clinician-supervised oral food challenge is the only definitive test
      available.

PMID- 24565540
TI  - Relationship of dog- and cat-specific IgE and IgG4 levels to allergic symptoms on
      pet exposure.
AB  - BACKGROUND: Environmental allergens may induce the generation of allergen
      specific IgE (sIgE) and IgG4 (sIgG4). Some studies report an association of sIgG4
      to protection against allergic symptoms after exposure to the relevant allergen.
      OBJECTIVE: We examined the relationship of dog and cat sIgE and sIgG4 levels to
      self-reported allergic symptoms on pet contact. METHODS: Participants 18 years of
      age in the Detroit Childhood Allergy Study cohort were asked whether they
      experienced symptoms on exposure to cats and dogs. Serum was assayed for cat and
      dog sIgE and sIgG4. Geometric means, ratios of cat and dog sIgE, sIgG4, and
      ratios of sIgG4/sIgE were compared between symptomatic and asymptomatic teens
      with the use of Wilcoxon rank sum tests. Ratios of sIgG4/sIgE, adjusted for
      presence of sIgE (>=0.35 kU/mL), were analyzed with logistic regression. RESULTS:
      Data on 500 participants were analyzed. Compared with asymptomatic teens, teens
      symptomatic with cat exposure had higher cat sIgE, sIgG4, and lower ratio of
      sIgG4/sIgE. Teens symptomatic after dog exposure had higher dog sIgE levels and
      lower sIgG4/sIgE, but similar levels of sIgG4 compared with asymptomatic
      participants. Increasing cat and dog sIgG4/sIgE ratios were associated with a
      lower likelihood of reporting allergic symptoms (cat: adjusted odds ratio, 0.8;
      95% CI, 0.6-0.9; dog: adjusted odds ratio, 0.8; 95% CI, 0.7-1.0). CONCLUSION:
      sIgG4 levels to cat and dog allergens correlate with lower rates of pet-induced
      allergic symptoms when interpreted in the context of concomitant sIgE. However,
      sIgG4 appears to have little utility as an isolated marker to indicate that pet
      exposure will be well tolerated.

PMID- 24565541
TI  - Effectiveness of subcutaneous versus sublingual immunotherapy for the treatment
      of allergic rhinoconjunctivitis and asthma: a systematic review.
AB  - BACKGROUND: Allergen-specific immunotherapy is widely used in the management of
      patients with allergic rhinoconjunctivitis and asthma, but the best route of
      delivery is unclear. OBJECTIVE: We performed a systematic review of studies with
      head-to-head comparison of effectiveness and safety of subcutaneous immunotherapy
      (SCIT) and sublingual immunotherapy (SLIT) in the treatment of allergic
      rhinoconjunctivitis and asthma. METHODS: MEDLINE, Embase, and the Cochrane
      Central Register of Controlled Trials databases were searched through December
      21, 2012. We included English language randomized controlled trials that enrolled
      patients with allergic rhinoconjunctivitis and/or asthma with head-to-head
      comparisons of SCIT with SLIT. Paired reviewers extracted detailed information
      from included articles on standardized forms and assessed the risk of bias in
      each article. RESULTS: Eight trials compared the effectiveness and safety of SCIT
      and SLIT. The effectiveness of the 2 forms of immunotherapy in managing allergic
      asthma and rhinoconjunctivitis were reported in 4 and 6 clinical trials,
      respectively. Low-grade evidence supports greater effectiveness of SCIT than SLIT
      for asthma symptom reduction and also at reducing a combined measure of rhinitis
      symptoms and medication use. Moderate-grade evidence supports greater
      effectiveness of SCIT than SLIT for nasal and/or eye symptom reduction. All 8
      trials reported on adverse events with an episode of anaphylaxis reported in a
      child treated with SCIT. CONCLUSION: Our review provides low-grade evidence to
      support that SCIT is superior to SLIT for reduction in asthma symptoms and
      moderate-grade evidence for reduction of allergic rhinoconjunctivitis. Additional
      studies are required to strengthen this evidence base for clinical decision
      making.

PMID- 24565543
TI  - Racial and ethnic disparity in food allergy in the United States: a systematic
      review.
AB  - BACKGROUND: The prevalence of food allergy is rising among US children. Little is
      known about racial/ethnic disparities in food allergy. OBJECTIVE: We performed a
      systematic literature review to understand racial/ethnic disparities in food
      allergy in the United States. METHODS: We searched PubMed/MEDLINE, Embase, and
      Scopus for original data about racial/ethnic disparities in the diagnosis,
      prevalence, treatment, or clinical course of food allergy or sensitization, with
      a particular focus on black (African American) race. Articles were analyzed by
      study methodology, racial/ethnic composition, food allergy definition, outcomes,
      summary statistic used, and covariate adjustment. RESULTS: Twenty of 645
      identified articles met inclusion criteria. The studies used multiple differing
      criteria to define food allergy, including self-report, sensitization assessed by
      serum food-specific IgE to selected foods without corroborating history,
      discharge codes, clinic chart review, and event-reporting databases. None used
      oral food challenge. In 12 studies, black persons (primarily children) had
      significantly increased adjusted odds of food sensitization or significantly
      higher proportion or odds of food allergy by self-report, discharge codes, or
      clinic-based chart review than white children. Major differences in study
      methodology and reporting precluded calculation of a pooled estimate of effect.
      CONCLUSION: Sparse and methodologically limited data exist about racial/ethnic
      disparity in food allergy in the United States. Available data lack a common
      definition for food allergy and use indirect measures of allergy, not food
      challenge. Although data suggest an increased risk of food sensitization, self
      reported allergy, or clinic-based diagnosis of food allergy among black children,
      no definitive racial/ethnic disparity could be found among currently available
      studies.

PMID- 24565542
TI  - Short-acting beta-agonist use as a marker of current asthma control.
AB  - BACKGROUND: The relationship between current asthma symptoms and rescue
      bronchodilator (reliever) use is uncertain, leading to different recommendations
      about the preferred reliever metric to use when assessing asthma control. In a 6
      month randomized controlled trial of combination budesonide/formoterol as
      maintenance and reliever therapy versus combination budesonide/formoterol as
      maintenance treatment with albuterol as reliever, we measured inhaler use by
      electronic monitoring. OBJECTIVE: To determine the agreement between current
      asthma symptoms and different metrics of albuterol use for patients randomly
      assigned to maintenance budesonide/formoterol treatment. METHODS: Data on
      albuterol use were extracted for the 7-day period before visit 2 (at week 3) from
      150 adult patients with asthma. Current asthma symptoms were measured by Asthma
      Control Questionnaire-5 (ACQ-5) score at the clinic visit. RESULTS: The number of
      days of albuterol use, the average number of albuterol actuations/day, and the
      highest number of albuterol actuations/day in the 1-week period were all
      positively associated with ACQ-5 score (r = 0.41-0.45, P < .001) and had moderate
      discrimination for well-controlled and not well-controlled asthma (ACQ-5 scores
      <=0.75 and >=1.5, respectively), with receiver operator characteristic area under
      the curve of 0.80 to 0.82 and 0.70 to 0.77, respectively. Cut points of >=3 days
      of albuterol use, average albuterol use of >=1 actuation/day, and highest
      albuterol use of >=4 actuations/day in the 1-week period had 73% sensitivity and
      62% specificity, 78% sensitivity and 67% specificity, and 78% sensitivity and 66%
      specificity, respectively, for predicting an ACQ-5 >=1.5. CONCLUSION: Our
      findings support the use of the number of days of albuterol use, the average
      number of albuterol actuations per day, and the highest number of albuterol
      actuations per day over a 1-week period of observation as comparable markers of
      current asthma control.

PMID- 24565544
TI  - Vocal cord dysfunction as demonstrated by impulse oscillometry.
AB  - BACKGROUND: Vocal cord dysfunction (VCD) is a respiratory disorder characterized
      by inappropriate vocal cord adduction during inspiration. The diagnosis of VCD is
      challenging, because expected flow volume loop abnormalities are uncommonly
      noted, and laryngoscopy must be timed to coincide with symptoms. OBJECTIVE: We
      wanted to determine the potential role of impulse oscillometry (IOS) in the
      diagnosis of VCD. METHODS: We conducted an analysis of six patients in which the
      diagnosis of VCD was being considered as well as seven healthy subjects and five
      subjects with asthma. All were evaluated with IOS and spirometry, and patients
      underwent laryngoscopy. Two patients with suspected VCD who did not exhibit
      symptoms or abnormal pulmonary function at baseline underwent exercise challenge
      and repeat studies. One patient with suspected VCD underwent an additional
      irritant challenge. RESULTS: VCD was diagnosed by laryngoscopy in three of the
      six patients in whom the diagnosis of VCD was entertained. These three patients
      as a group all exhibited higher amplitude (mean, 9.3 cm H20/L/second) and more
      variable spikes (SD, 4.8 cm H20/L/second) on IOS impedance during inspiration,
      whereas the three patients in whom the diagnosis was not confirmed by endoscopy
      did not show these findings (mean, 2.0 cm H20/L/second; P < .0002; SD, 0.8 cm
      H20/L/second; P < .0001). This pattern was also not observed in the healthy
      volunteers (mean +/- SD, 1.8 +/- 0.7 cm H20/L/second) and patients with asthma at
      baseline (mean, 4.2 +/- 1.2 cm H20/L/second) or after exercise challenge (mean,
      1.5 +/- 0.5 cm H20/L/second). CONCLUSIONS: These findings support the conclusion
      that IOS displays a characteristic pattern in patients with VCD and thus may
      offer a rapid and noninvasive adjunct to the assessment and diagnosis of patients
      suspected to have this disorder.

PMID- 24565546
TI  - A child with allergic contact dermatitis due to para-phenylenediamine.

PMID- 24565545
TI  - The value of specific IgE to peanut and its component Ara h 2 in the diagnosis of
      peanut allergy.
AB  - BACKGROUND: To avoid unnecessary oral food challenges, which are time consuming,
      stressful, and risky, improved in vitro diagnostic methods for food allergy such
      as component resolved diagnostics are still under investigation. OBJECTIVE: To
      investigate the role of whole peanut- and peanut-component (Ara h 1, Ara h 2, Ara
      h 3, Ara h 6 and Ara h 8)-specific IgE levels in the diagnostic procedure of
      peanut allergy as well as the diagnostic properties of peanut-specific IgG and
      IgG4. METHODS: Sixty-one children underwent oral peanut challenge tests for
      diagnostic purposes irrespective of their peanut-specific IgE levels. Peanut
      specific serum IgE, IgG, and IgG4 levels were determined by ImmunoCAP FEIA and
      specific IgE against individual peanut proteins by Immuno Solid-phase Allergen
      Chip. RESULTS: Thirty-four of 61 patients (56%) had a peanut allergy. No
      significant difference was observed for peanut-specific IgG or peanut-specific
      IgG4 levels between patients who were allergic and tolerant patients, whereas
      peanut-specific IgE was significant higher in patients who were allergic than in
      tolerant patients (P < .005). Twenty-five of 61 children had peanut-specific IgE
      above a previously proposed cutoff level of 15 kUA/L; however, 7 of these 25
      children (28%) were clinically tolerant. Ara h 2-specific IgE was significantly
      lower in tolerant than in patients with allergies (P < .0001). Interestingly, 94%
      of the patients with peanut allergies showed IgE-binding to Ara h 2.
      Unfortunately, 26% of the sensitized but tolerant patients have shown IgE binding
      to Ara h 2 too. CONCLUSIONS: Neither the level of specific IgE to peanut nor to
      Ara h 2 was able to clearly distinguish patients with clinical relevant peanut
      allergy from those who were clinical tolerant in our population. As expected,
      peanut-specific IgG and IgG4 did not improve the diagnostic procedure.

PMID- 24565547
TI  - Foods with precautionary allergen labeling in Australia rarely contain detectable
      allergen.

PMID- 24565548
TI  - Treatment of postviral nonasthmatic cough with corticosteroids.

PMID- 24565549
TI  - A case of a false-positive screen for severe combined immunodeficiency in
      Pennsylvania, a state without statewide screening.

PMID- 24565550
TI  - Ceftazidime-induced drug reaction with eosinophilia and systemic symptoms (DRESS)
      complicated by hemophagocytic lymphohistiocytosis.

PMID- 24565551
TI  - Opportunistic infections in a patient with HIV and thymoma.

PMID- 24565552
TI  - Anaphylaxis to cat in a child with exclusive sensitivity to Fel d 1.

PMID- 24565553
TI  - Heating does not decrease immunogenicity of goat's and ewe's milk.

PMID- 24565554
TI  - Intolerance to sweet treats in a child.

PMID- 24565555
TI  - Re: does omitted history misrepresent OIT role for food allergy today?

PMID- 24565556
TI  - Reply: To PMID 24229817.

PMID- 24565559
TI  - Novel cetacean morbillivirus in Guiana dolphin, Brazil.

PMID- 24565561
TI  - SREBP-1c overexpression induces triglycerides accumulation through increasing
      lipid synthesis and decreasing lipid oxidation and VLDL assembly in bovine
      hepatocytes.
AB  - The natural incidence of fatty liver in ruminants is significantly higher than in
      monogastric animals. Fatty liver is associated with sterol regulatory element
      binding protein 1c (SREBP-1c). The aim of this study was to investigate the
      regulatory network effects of SREBP-1c on the lipid metabolic genes involved in
      fatty acid uptake, activation, oxidation, synthesis, and very low-density
      lipoprotein (VLDL) assembly in bovine hepatocytes. In vitro, bovine hepatocytes
      were transfected with an adenovirus-mediated SREBP-1c overexpression vector.
      SREBP-1c overexpression significantly up-regulated the expression and activity of
      the fatty acid uptake, activation, and synthesis enzymes: liver fatty acid
      binding protein, fatty acid translocase, acyl-CoA synthetase long-chain 1, acetyl
      CoA carboxylase 1, and fatty acid synthase, increasing triglyceride (TG)
      synthesis and accumulation. SREBP-1c overexpression down-regulated the expression
      and activity of the lipid oxidation enzymes: carnitine palmitoyltransferase 1 and
      carnitine palmitoyltransferase 2. Furthermore, the apolipoprotein B100 expression
      and microsomal triglyceride transfer protein activity were significantly
      decreased. SREBP-1c overexpression reduced lipid oxidation and VLDL synthesis,
      thereby decreasing TG disposal and export. Therefore, large amounts of TG
      accumulated in the bovine hepatocytes. Taken together, these results indicate
      that SREBP-1c overexpression increases lipid synthesis and decreases lipid
      oxidation and VLDL export, thereby inducing TG accumulation in bovine
      hepatocytes. 

PMID- 24565560
TI  - Regulation of the human cathelicidin antimicrobial peptide gene by 1alpha,25
      dihydroxyvitamin D3 in primary immune cells.
AB  - Production of the human cathelicidin antimicrobial peptide gene (hCAP18/LL-37),
      is regulated by 1alpha,25-dihydroxyvitamin D3 (1,25D3) and is critical in the
      killing of pathogens by innate immune cells. In addition, secreted LL-37 binds
      extracellular receptors and modulates the recruitment and activity of both innate
      and adaptive immune cells. Evidence suggests that during infections activated
      immune cells locally produce increased levels of 1,25D3 thus increasing
      production of hCAP18/LL-37. The relative expression levels of hCAP18/LL-37 among
      different immune cell types are not well characterized. The aim of this study was
      to determine the relative levels of hCAP18/LL-37 in human peripheral blood immune
      cells and determine to what extent 1,25D3 increased its expression in peripheral
      blood-derived cells. We show for the first time, a hierarchy of expression of
      hCAP18 in freshly isolated cells with low levels in lymphocytes, intermediate
      levels in monocytes and the highest levels found in neutrophils. In peripheral
      blood-derived cells, the highest levels of hCAP18 following treatment with 1,25D3
      were in macrophages, while comparatively lower levels were found in GM-CSF
      derived dendritic cells and osteoclasts. We also tested whether treatment with
      parathyroid hormone in combination with 1,25D3 would enhance hCAP18 induction as
      has been reported in skin cells, but we did not find enhancement in any immune
      cells tested. Our results indicate that hCAP18 is expressed at different levels
      according to cell type and lineage. Furthermore, potent induction of hCAP18 by
      1,25D3 in macrophages and dendritic cells may modulate functions of both innate
      and adaptive immune cells at sites of infection. 

PMID- 24565563
TI  - Combined administration of curcumin and gallic acid inhibits gallic acid-induced
      suppression of steroidogenesis, sperm output, antioxidant defenses and
      inflammatory responsive genes.
AB  - In this study, we investigated the effects of administration of gallic acid (Gal)
      with or without curcumin (Cur) on the sperm output, steroid level and antioxidant
      defenses in rat testis in vivo and the expression of inflammatory responsive
      genes in vitro. Male Wistar rats were divided randomly into four groups and given
      oral Gal (100mg/kg/day) and Cur (100mg/kg/day) alone or in combination for four
      weeks. The sperm quality was impaired following Gal treatment, while Cur
      prevented this and also improved the sperm count as well as the efficiency of
      sperm production (DSP/gm testis). The inhibitory effects of Gal on plasma
      testosterone level, glutathione levels, activities of glutathione peroxidase,
      catalase, superoxide dismutase and steroidogenic enzymes, 3beta-hydroxysteroid
      dehydrogenase (3beta-HSD) and 17beta-HSD in the rat testis was blocked by Cur.
      Interestingly, the level of testosterone and the activities of the steroidogenic
      enzymes were significantly increased after treatment with Cur alone.
      Malondialdehyde concentration was unchanged following Gal treatment, while a
      significant decrease in malondialdehyde level was observed following treatment
      with Cur alone or in combination with Gal. We further analyzed the effects of Cur
      and Gal (25-100 MUM) on the 93RS2 Sertoli cell-lines and observed that Cur
      blocked the Gal-induced suppression of inflammatory mediators such as TNF-alpha
      and IL-6, while Gal blocked the suppressive effect of Cur on IL-1alpha
      expression. Furthermore, the stimulatory or inhibitory effects of Gal on the
      expressions Tgf-beta1 and CD-14 was concentration-dependent and could be blocked
      by Cur. When cultures of primary Sertoli cells were exposed to both Cur and Gal
      for 24h, p-JNK/SAPK expression remain stable, whereas Gal-induced p-p65 (NF
      kappaB) expression and IkappaBalpha degradation was seen to be blocked by Cur but
      not Gal-induced expression of pERK1/2. Overall, Cur has stimulatory reproductive
      effects and could protect the testis from the toxic effects of Gal by mechanisms
      that could not be explained by its effects on the expressions of inflammatory
      cytokines but by its anti-oxidant properties.

PMID- 24565564
TI  - Identification of an anabolic selective androgen receptor modulator that actively
      induces death of androgen-independent prostate cancer cells.
AB  - Prostate cancer (PCa) initially responds to inhibition of androgen receptor (AR)
      signaling, but inevitably progresses to hormone ablation-resistant disease. Much
      effort is focused on optimizing this androgen deprivation strategy by improving
      hormone depletion and AR antagonism. However we found that bicalutamide, a
      clinically used antiandrogen, actually resembles a selective AR modulator (SARM),
      as it partially regulates 24% of endogenously 5alpha-dihydrotestosterone (DHT)
      responsive genes in AR(+) MDA-MB-453 breast cancer cells. These data suggested
      that passive blocking of all AR functions is not required for PCa therapy. Hence,
      we adopted an active strategy that calls for the development of novel SARMs,
      which induce a unique gene expression profile that is intolerable to PCa cells.
      Therefore, we screened 3000 SARMs for the ability to arrest the androgen
      independent growth of AR(+) 22Rv1 and LNCaP PCa cells but not AR(-) PC3 or DU145
      cells. We identified only one such compound; the 4-aza-steroid, MK-4541, a potent
      and selective SARM. MK-4541 induces caspase-3 activity and cell death in both
      androgen-independent, AR(+) PCa cell lines but spares AR(-) cells or AR(+) non
      PCa cells. This activity correlates with its promoter context- and cell-type
      dependent transcriptional effects. In rats, MK-4541 inhibits the trophic effects
      of DHT on the prostate, but not the levator ani muscle, and triggers an anabolic
      response in the periosteal compartment of bone. Therefore, MK-4541 has the
      potential to effectively manage prostatic hypertrophic diseases owing to its
      antitumor SARM-like mechanism, while simultaneously maintaining the anabolic
      benefits of natural androgens. 

PMID- 24565565
TI  - The selective glucocorticoid receptor modulator CORT108297 restores faulty
      hippocampal parameters in Wobbler and corticosterone-treated mice.
AB  - Mutant Wobbler mice are models for human amyotrophic lateral sclerosis (ALS). In
      addition to spinal cord degeneration, Wobbler mice show high levels of blood
      corticosterone, hyperactivity of the hypothalamic-pituitary-adrenal axis and
      abnormalities of the hippocampus. Hypersecretion of glucocorticoids increase
      hippocampus vulnerability, a process linked to an enriched content of
      glucocorticoid receptors (GR). Hence, we studied if a selective GR antagonist
      (CORT108297) with null affinity for other steroid receptors restored faulty
      hippocampus parameters of Wobbler mice. Three months old genotyped Wobbler mice
      received s.c. vehicle or CORT108297 during 4 days. We compared the response of
      doublecortin (DCX)+ neuroblasts in the subgranular layer of the dentate gyrus
      (DG), NeuN+ cells in the hilus of the DG, glial fibrillary acidic protein (GFAP)+
      astrocytes and the phenotype of Iba1+ microglia in CORT108297-treated and vehicle
      treated Wobblers. The number of DCX+ cells in Wobblers was lower than in control
      mice, whereas CORT108297 restored this parameter. After CORT108297 treatment,
      Wobblers showed diminished astrogliosis, and changed the phenotype of Iba1+
      microglia from an activated to a quiescent form. These changes occurred without
      alterations in the hypercorticosteronemia or the number of NeuN+ cells of the
      Wobblers. In a separate experiment employing control NFR/NFR mice, treatment with
      corticosterone for 5 days reduced DCX+ neuroblasts and induced astrocyte
      hypertrophy, whereas treatment with CORT108297 antagonized these effects.
      Normalization of neuronal progenitors, astrogliosis and microglial phenotype by
      CORT108297 indicates the usefulness of this antagonist to normalize hippocampus
      parameters of Wobbler mice. Thus, CORT108297 opens new therapeutic options for
      the brain abnormalities of ALS patients and hyperadrenocorticisms. 

PMID- 24565562
TI  - Estrogen signaling crosstalk: Implications for endocrine resistance in ovarian
      cancer.
AB  - Resistance to anti-estrogen therapies is a prominent challenge in the treatment
      of ovarian cancer. Tumors develop endocrine resistance by acquiring adaptations
      that help them rely on alternative oncogenic signaling cascades, which crosstalk
      with estrogen signaling pathways. An understanding of estrogen signaling
      crosstalk with these growth promoting cascades is essential in order to maximize
      efficacy of anti-estrogen treatments in ovarian cancer. Herein, we provide an
      overview of estrogen signaling in ovarian cancer and discuss the major challenges
      associated with anti-estrogen therapies. We also review what is currently known
      about how genomic and non-genomic estrogen signaling pathways crosstalk with
      several major oncogenic signaling cascades. The insights provided here illustrate
      existing strategies for targeting endocrine resistant ovarian tumors and may help
      identify new strategies to improve the treatment of this disease. 

PMID- 24565566
TI  - Pomegranate extracts impact the androgen biosynthesis pathways in prostate cancer
      models in vitro and in vivo.
AB  - Castration-resistant prostate cancer (CRPC) remains largely dependent on androgen
      receptor (AR). Residual tissue androgens are consistently detected within CRPC
      tumors and play a critical role in facilitating AR-mediated signaling pathways
      which lead to disease progression. Testosterone and dihydrotestosterone (DHT) are
      the major androgens detected in tumors. They are produced through three
      biosynthesis pathways: Delta(4), Delta(5), and backdoor pathways. Both androgens
      bind to and stimulate AR activation. The current study investigates the effects
      of pomegranate extracts (POM) and their ability to inhibit androgen biosynthesis
      using PCa cell lines (22RV1 and LNCaP) in vitro as well as the PTEN knockout
      mouse model representing prostate cancer. Steroids were extracted using ethyl
      acetate or solid phase extraction, and then analyzed by UPLC/MS/MS. The results
      showed that POM (0-12MUg/mL) reduced the production of testosterone, DHT, DHEA,
      androstenedione, androsterone, and pregnenolone in both cell lines. In addition
      our in vivo data supports this observation with a reduction in serum steroids
      determined after 20 weeks of POM treatment (0.17 g/L in drinking water). In
      accordance with these results, Western blotting of cell lysates and tPSA analysis
      determined that PSA was significantly decreased by the treatment of POM.
      Interestingly, AKR1C3 and AR levels were shown to be increased in both cell
      lines, perhaps as a negative feedback effect in response to steroid inhibition.
      Overall, these results provide mechanistic evidence to support the rationale for
      recent clinical reports describing efficacy of POM in CRPC patients.

PMID- 24565567
TI  - [PET and SPECT in epilepsy].
AB  - Epilepsy is one of the most frequent chronic neurological disorders, affecting 1
      2% of the population. Patients with complex partial drug resistant episodes may
      benefit from a surgical treatment consisting in the excision of the epileptogenic
      area. Localization of the epileptogenic area was classically performed with video
      EEG and magnetic resonance (MR). Recently, functional neuroimaging studies of
      Nuclear Medicine, positron emission tomography (PET) and single photon emission
      tomography (SPECT) have demonstrated their utility in the localization of the
      epileptogenic area prior to surgery. Ictal SPECT with brain perfusion tracers
      show an increase in blood flow in the initial ictal focus, while PET with (18)FDG
      demonstrates a decrease of glucose metabolism in the interictal functional
      deficit zone. In this review, the basic principles and methodological
      characteristics of the SPECT and PET in epilepsy are described. The ictal SPECT
      injection mechanism, different patterns of perfusion based on the time of ictal,
      postictal or interictal injection are detailed and the different diagnostic
      sensitivities of each one of these SPECT are reviewed. Different methods of
      analysis of the images with substraction and fusion systems with the MR are
      described. Similarly, the injection methodology, quantification and evaluation of
      the images of the PET in epilepsy are described. Finally, the main clinical
      indications of SPECT and PET in temporal and extratemporal epilepsy are detailed.

PMID- 24565568
TI  - Integration of automated morphological features resolves a distinct group of
      atypical chronic lymphocytic leukemias with chromosomal aberrations.
AB  - Automated morphological assessment of peripheral blood slides has become an
      important modality facilitating characterization and quantification of cells in a
      uniform, fast and robust manner. In this study, we evaluated the morphological
      diversity in peripheral blood films of 94 chronic lymphocytic leukemia (CLL)
      patients using the DM1200 CellaVision automated microscopy system. Aberrant
      lymphocytes and smudge cells were enumerated and correlated with CLL
      immunophenotype, chromosomal aberrations and prognostic parameters. Herein, we
      show that the percentages of aberrant and smudge cells was highly variable
      between patients and did not correlate with each other. Increased aberrant
      lymphocytes and fewer smudge cells were associated with an atypical
      immunophenotype including low expression of CD23, higher levels of FMC7 and
      bright surface levels of CD20. High fraction of aberrant lymphocytes also was
      associated with trisomy 12. These cells were predominantly of small/medium size,
      sometimes with cleft nuclei. No correlation was noted between aberrant or smudge
      cells and clinical stage, CD38, ZA70 or time to first treatment. Taken together,
      automated morphological analysis of peripheral blood leukocytes emerged as a
      powerful and robust tool for the quantitative morphological stratification of
      CLL. Integration of the automated morphological features discriminates between
      different CLL phenotypes and distinct chromosomal aberrations. 

PMID- 24565569
TI  - Synthesis of febrifugine derivatives and development of an effective and safe
      tetrahydroquinazoline-type antimalarial.
AB  - Febrifugine, a quinazoline alkaloid isolated from Dichroa febrifuga roots, shows
      powerful antimalarial activity against Plasmodium falciparum. Although the use of
      ferifugine as an antimalarial drug has been precluded because of its severe side
      effects, its potent antimalarial activity has stimulated medicinal chemists to
      pursue its derivatives instead, which may provide valuable leads for novel
      antimalarial drugs. In the present study, we synthesized new derivatives of
      febrifugine and evaluated their in vitro and in vivo antimalarial activities to
      develop antimalarials that are more effective and safer. As a result, we proposed
      tetrahydroquinazoline-type derivative as a safe and effective antimalarial
      candidate.

PMID- 24565570
TI  - Synthesis, neuronal activity and mechanisms of action of halogenated enaminones.
AB  - Due to the excellent anticonvulsant activity of previously synthesized
      halogenated enaminones, more disubstituted analogs were synthesized and evaluated
      in vitro. The new enaminones either had no effect, depressed, or enhanced
      population spike (PS) amplitude in the rat hippocampus in a concentration
      dependent manner. Structure-activity relationship (SAR) analysis indicated that
      compounds 21 and 25 (with dibromo substituents) were equipotent, and more potent
      than compound 2 (with dichloro substituents), with compound 25 being the most
      efficacious of all tested compounds. Both diiodo derivatives 30 and 31 tested
      produced no significant effect on PS. For PS depression, phenyl substitution on
      the cyclohexenone ring produced the most efficacious compound 25. PS depressing
      analogues also depressed evoked excitatory postsynaptic current (EPSC) and action
      potential firing frequency. Removal of phenyl or methyl group from position 6 on
      the cyclohexenone ring of enaminone esters produced compound 28 which exhibited
      pro-convulsant effects. There was no direct correlation between C log P values
      and anticonvulsant activity of the halogenated enaminones. The mechanisms of
      anticonvulsant activity were the indirect suppression of excitatory synaptic
      transmission by enhancing extracellular GABA, and the direct suppression of
      action potential firing of the neurons.

PMID- 24565571
TI  - Multifunctional compounds: smart molecules for multifactorial diseases.
AB  - Multifunctional compounds (MFCs) are designed broadly as hybrid or conjugated
      drugs or as chimeric drugs from two or more pharmacophores/drugs having specific
      pharmacological activities. These are capable of eliciting multiple
      pharmacological actions and have emerged as magic bullets in treatment of
      multifactorial diseases. Many research articles disclosing the development of
      such compounds for treatment of multifactorial diseases are published during last
      7 years. Some successful MFC candidates for multifactorial CNS disorders include
      ziprasidone, duloxetine, ladostigil and M-30 whereas sunitinib, lapatinib and
      synthetic oleandane triterpinoids are the successful MFC candidates for various
      cancers. Many more compounds derived from berberine, tacrine, artemisnin,
      quinine, NSAIDs, pralidoxine, donepezil, rivastigmine, curcumin and various
      antioxidants are under investigations for exploration of their multifunctional
      potential. In general, MFCs possess the advantages of reduced molecularity, no
      drug-drug interactions and improved pharmacokinetics and pharmacodynamics. A MFC
      derived from two or more different pharmacophores exerts its activities by
      interacting with respective receptors of its constituent pharmacophores. It may
      also exhibit additional binding interactions with the receptor sites that may be
      responsible for significantly improved or additional activities. The present
      review discusses various MFCs developed for specific class of disorders with an
      aim to provide an insight into the strategies in medicinal chemistry for
      development of such compounds.

PMID- 24565572
TI  - Amphiphilic cationic carbosilane-PEG dendrimers: synthesis and applications in
      gene therapy.
AB  - Here we synthesized carbosilane, generation 1 to 3, and PEG-based dendrons
      functionalized at the periphery with NHBoc groups and at the focal point with
      azide and alkyne moieties, respectively. The coupling of these two types of
      dendrons via click chemistry led to the formation of new hybrid dendrimers with
      two distinct moieties, the hydrophobic carbosilane and the hydrophilic PEG-based
      dendron. The protected dendrimers were transformed into cationic ammonium
      dendrimers. These unique amphiphilic dendrimers were studied as vectors for gene
      therapy against HIV in peripheral blood mononuclear cells (PBMC) and their
      performance was compared with that of a PEG-free carbosilane dendrimer. The
      presence of the PEG moiety afforded lower toxicities and evidenced a weaker
      interaction between dendrimers and siRNA when compared to the homodendrimer
      analogous. Both features, lower toxicity and lower dendriplex strength, are key
      properties for use of these vectors as carriers of nucleic material. 

PMID- 24565573
TI  - 4,5,6,7-Tetrahydro-isoxazolo-[4,5-c]-pyridines as a new class of cytotoxic Hsp90
      inhibitors.
AB  - Hsp90 is considered an interesting therapeutic target for anticancer drug
      development. Here we describe a new class of 4,5,6,7-tetrahydro-isoxazolo-[4,5-c]
      pyridine compounds. A small library of derivatives has been synthesized and
      investigated. Some reported compounds show interesting properties combining both
      notable binding to Hsp90 and potent cell growth inhibitory activity. N-5
      substitution with a 2,4 resorcinol carboxamide appears crucial for activity.
      Moreover, a derivative bearing a hydroxamic acid residue bound to C-3 amide
      portion was found to inhibit both Hsp90 and HDAC6.

PMID- 24565574
TI  - Exponential state estimation of Markovian jumping genetic regulatory networks
      with mode-dependent probabilistic time-varying delays.
AB  - In this paper, we investigate a problem of exponential state estimation for
      Markovian jumping genetic regulatory networks with mode-dependent probabilistic
      time-varying delays. A new type of mode-dependent probabilistic leakage time
      varying delay is considered. Given the probability distribution of the time
      delays, stochastic variables that satisfying Bernoulli random binary distribution
      are formulated to produce a new system which includes the information of the
      probability distribution. Under these circumstances, the state estimator is
      designed to estimate the true concentration of the mRNA and the protein of the
      GRNs. Based on Lyapunov-Krasovskii functional that includes new triple integral
      terms and decomposed integral intervals, delay-distribution-dependent exponential
      stability criteria are obtained in terms of linear matrix inequalities. Finally,
      a numerical example is provided to show the usefulness and effectiveness of the
      obtained results. 

PMID- 24565575
TI  - The "paradigm of abundance" in clinical oncology practice: a new agony and
      ecstasy?

PMID- 24565576
TI  - Reducing lung cancer mortality: 2014 update.

PMID- 24565578
TI  - Invasive and noninvasive advances in the staging of lung cancer.
AB  - Accurate staging of lung cancer is crucial to ensure the validity of lung cancer
      clinical research efforts and constitutes the cornerstone of the management of
      affected patients. The last decade has witnessed unprecedented technological
      advances allowing for more accurate and less invasive staging. In general, these
      techniques should be viewed as complementary rather than competitive, and
      indications, contraindications, and limitations of all staging techniques should
      be fully understood by providers involved with lung cancer patients. Noninvasive
      imaging techniques include chest computed tomography (CT) and positron emission
      tomography (PET). Invasive techniques can be nonsurgical such as needle-based
      techniques (endobronchial or endoscopic ultrasound) or surgical (mediastinoscopy
      and variants). The necessary multidisciplinary approach to lung cancer patients
      dictates that all stakeholders be familiar with the benefits and limitations of
      these newer techniques. 

PMID- 24565579
TI  - Genes and pathology of non-small cell lung carcinoma.
AB  - While histopathology has traditionally been the cornerstone of treatment
      decisions in the management of lung cancer patients, the complexity and
      heterogeneity of histological classification has had a limited impact in the
      routine practice of oncology. This has changed dramatically in the last few
      years, owing to discoveries of genomic aberrations and results of clinical trials
      of novel and targeted therapies. These discoveries have resulted in a new way of
      classifying non-small cell lung cancer (NSCLC), based on the occurrence of
      putative or proven driver and targetable genomic changes. The rapidity by which
      the landscape of mutation and genomic changes is being identified also has led to
      a new paradigm and approaches to pathological diagnosis of NSCLC. In this
      context, international consortia have proposed new classifications of lung
      adenocarcinoma and guidelines for molecular testing in lung cancer and have
      provided concrete recommendations on new ways to practice lung cancer pathology. 

PMID- 24565577
TI  - Estrongenic steroid hormones in lung cancer.
AB  - It is becoming increasingly clear that steroid hormones are involved in the
      biology of many organs outside the reproductive system. Evidence has been
      accumulating since the mid 1990s that the lung contains receptors for both
      estrogen and progesterone and that these hormones have some role in lung
      development, pulmonary inflammation, and lung cancer. The estrogen receptor beta
      (ERbeta) is the major ER expressed in lung tissues, while inflammatory cells
      capable of infiltrating the lung are reported to express both ERalpha and ERbeta.
      Although there is evidence in animals of preferential effects of ERbeta in the
      lungs of females, human lung tumors from males also contain ERbeta-positive cells
      and express aromatase, the enzyme that converts testosterone to estrogens. This
      review will discuss current literature findings on the role of the ERs and the
      progesterone receptor (PR), as well CYP19 (aromatase), the rate-limiting enzyme
      in the synthesis of estrogen, in lung cancer. 

PMID- 24565580
TI  - Early-stage non-small cell lung cancer: surgery, stereotactic radiosurgery, and
      individualized adjuvant therapy.
AB  - Despite cures in early stage (IA-IIB) non-small cell lung cancer (NSCLC), the 5
      year survival rate is only 36%-73%. Surgical resection via lobectomy is the
      treatment of choice in early-stage NSCLC, with the goal being complete anatomic
      resection of the tumor and mediastinal lymph node evaluation. Newer technologies,
      including the minimally invasive thoracoscopic approach and the many techniques
      available to stage the mediastinum, have introduced advantages over traditional
      approaches in achieving this goal. The advent of stereotactic ablative
      radiotherapy (SABR) has changed how we treat those patients who cannot undergo
      surgery secondary to comorbidities or patient preference. SABR allows for precise
      radiation delivery in a short course and at high doses. Adjuvant cisplatin-based
      chemotherapy is the standard of care for completely resected high-risk stage IB
      and stage II NSCLC based on a ~5% improvement in 5-year overall survival. The
      concept of customized adjuvant chemotherapy is emerging, and we will explore the
      potential value of targeting tumor mutations with available drugs (ie, epidermal
      growth factor receptor [EGFR] mutations with erlotinib), a strategy that for the
      moment should be restricted to clinical trials. 

PMID- 24565581
TI  - Radiation therapy as a backbone of treatment of locally advanced non-small cell
      lung cancer.
AB  - Locally advanced non-small cell lung cancer (LA-NSCLC) is a heterogeneous
      disease, encompassing stage IIIA, for which surgery in combination with
      chemotherapy and/or radiation therapy (RT) represents a potential treatment
      approach for select patients, and stage IIIB, for which chemoradiation represents
      the standard of care. Recent advances in systemic cytotoxic and molecularly
      targeted therapies coupled with technologic innovations in radiotherapy have the
      potential to improve outcomes for this patient population. Many ongoing clinical
      trials use specific genetic mutations or histologic status to determine the
      combination of targeted therapies and RT, as well as to determine the optimal
      chemoradiotherapy platforms. Additionally, use of modern RT techniques has
      improved outcomes for some patients with limited metastatic disease, thereby
      prompting further studies on how to best integrate aggressive management of
      oligometastases using RT with chemotherapeutic regimens. 

PMID- 24565582
TI  - Extending survival of stage IV non-small cell lung cancer.
AB  - Most of patients with newly diagnosed non-small cell lung cancer (NSCLC) present
      with locally advanced or metastatic disease. In this setting the goal of
      treatment is to prolong survival and to control disease- and treatment-related
      symptoms. Currently systemic cytotoxic chemotherapy remains the first-line
      treatment for most patients with stage IV NSCLC, but preferred treatments are now
      defined by histology and based on the presence of specific molecular
      abnormalities. In first-line the combination of platinum plus pemetrexed with or
      without bevacizumab is a reasonable choice in patients with non-squamous NSCLC.
      Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) as
      first-line therapy are the recommended for patients with EGFR-sensitizing
      mutations. A small-molecule TKI of anaplastic lymphoma kinase (ALK), crizotinib,
      showed pronounced clinical activity in the treatment of patients with NSCLC
      positive for EML4-ALK and it has rapidly entered into daily clinical practice.
      Currently no agents are specifically approved for the treatment of squamous cell
      carcinoma of the lung. Second-line treatments include docetaxel, pemetrexed, or
      erlotinib as single agents. There is a growing evidence that cytotoxics are
      better than EGFR-TKIs in EGFR wild-type patients. In the setting of the third
      line, the only approved agent is erlotinib. In elderly patients with good
      performance status (PS), doublet chemotherapy including platinum should not be
      excluded, especially for those patients 70-75 years of age without comorbidities.
      The better selection of patients, the identification of specific predictive
      biomarkers, a reasonable sequencing of all active and available treatments,
      including targeted therapies and cytotoxic, may significantly contribute to
      extend the natural history of stage IV NSCLC. 

PMID- 24565583
TI  - Chemotherapy and targeted therapeutics as maintenance of response in advanced non
      small cell lung cancer.
AB  - Non-small cell lung cancer (NSCLC) remains the most common cause of cancer
      related death in the United States. Survival for patients with advanced disease
      remains meager with standard platinum-based doublet therapy even given initially.
      Improved efficacy and tolerability of third-generation chemotherapies and small
      molecule inhibitors has prompted the evaluation of these agents in the
      maintenance setting in order to enhance current outcomes. Two separate strategies
      have evolved: the introduction of a non-cross-resistant drug immediately
      following first-line or induction chemotherapy (switch maintenance), or the
      continuation of the non-platinum partner initially introduced during induction
      (continuation maintenance). Here we review the available clinical trial data
      evaluating both maintenance strategies, and offer our assessment of their
      contemporary clinical implications and cost-effectiveness. 

PMID- 24565584
TI  - Targeting epidermal growth factor receptor in the management of lung cancer.
AB  - The epidermal growth factor receptor (EGFR) mutation is a potent oncogenic driver
      that accounts for carcinogenesis and tumor growth of pulmonary adenocarcinoma.
      Targeting EGFR with tyrosine kinase inhibitors (TKIs) is highly effective in
      terms of tumor response rate, progression-free survival (PFS), and quality of
      life. Multiple randomized studies have confirmed the superiority of EGFR TKIs
      over platinum-based chemotherapy and established EGFR TKIs as standard first-line
      therapy for patients with EGFR mutation-positive non-small cell lung cancer
      (NSCLC). However, almost all patients will develop resistance to EGFR TKIs and
      post progression therapy may include a combination of local therapy, systemic
      chemotherapy, and second-generation EGFR TKIs. 

PMID- 24565586
TI  - Immune checkpoint blockade: the hope for immunotherapy as a treatment of lung
      cancer?
AB  - Over the past 20 years, immunotherapy has not played a role in the treatment of
      lung cancer outside of clinical trials. Early trials with vaccines yielded
      promising results, but phase III trials have yet to show an improvement in
      survival. Recently, immune checkpoint pathway inhibitors have yielded exciting
      and consistent activity across this class of antibodies. However, phase III
      trials are now ongoing. Currently, the hope of bringing immunotherapy to lung
      cancer patients lies in this class of drugs. Only time will show us if these
      antibodies will yield an improvement in long-term survival. This review will
      focus on checkpoint pathway inhibitors that have completed early-phase trials. 

PMID- 24565588
TI  - High-risk myeloma: when to transplant-or not.

PMID- 24565585
TI  - Targeted therapies in non-small cell lung cancer: emerging oncogene targets
      following the success of epidermal growth factor receptor.
AB  - The diagnostic testing, treatment and prognosis of non-small cell lung cancer
      (NSCLC) has undergone a paradigm shift since the discovery of sensitizing
      mutations in the epidermal growth factor receptor (EGFR) gene in a subset of
      NSCLC patients. Several additional oncogenic mutations, including gene fusions
      and amplifications, have since been discovered, with a number of drugs that
      target each specific oncogene. This review focuses on oncogenes in NSCLC other
      than EGFR and their companion "targeted therapies." Particular emphasis is placed
      on the role of ALK, ROS1, RET, MET, BRAF, and HER2 in NSCLC. 

PMID- 24565587
TI  - Small cell lung cancer: therapies and targets.
AB  - Small cell lung cancer (SCLC) remains a fatal disease due to limited therapeutic
      options. Systemic chemotherapy is the bedrock of treatment for both the limited
      and extensive stages of the disease. However, the established management paradigm
      of platinum-based chemotherapy has reached an efficacy plateau. A modest survival
      improvement, approximately 5%, was witnessed with the addition of cranial or
      thoracic radiation to systemic chemotherapy. Other strategies to improve outcome
      of platinum-based chemotherapy in the last two decades have met with minimal
      success. The substitution of irinotecan for etoposide in the frontline treatment
      of SCLC achieved significant efficacy benefit in Japanese patients, but similar
      benefit could not be reproduced in other patient populations. Salvage treatment
      for recurrent or progressive SCLC is particularly challenging, where topotecan
      remains the only agent with regulatory approval to date. Ongoing evaluation of
      biologic agents targeting angiogenesis, sonic hedgehog pathway, DNA repair
      pathway, and immune checkpoint modulators hold some promise for improved outcome
      in SCLC. It is hoped that the coming decade will witness the application of new
      molecular biology and genomic research techniques to improve our understanding of
      SCLC biology and identification of molecular subsets that can be targeted
      appropriately using established and emerging biological agents similar to the
      accomplishments of the last decade with non-small cell lung cancer (NSCLC). 

PMID- 24565590
TI  - Evaluating hematuria: impact of guideline adherence on urologic cancer diagnosis.
AB  - PURPOSE: The purpose of this study was to assess physician adherence to 2001
      American Urological Association (AUA) guidelines for evaluating patients with
      asymptomatic hematuria and its impact on the diagnosis of urologic cancer.
      METHODS: In this institutional review board-approved retrospective study of
      patients with asymptomatic hematuria evaluated in a large academic health center
      in 2004 (allowing for long-term follow-up), we randomly selected 100 of 1771
      patients with asymptomatic hematuria (52 men; mean age 54 years; 58 microscopic,
      39 macroscopic, three unknown-type hematuria; median follow-up 89 months,
      interquartile range 33-97 months). Multivariate logistic regression assessed
      effects of age, sex, hematuria type, and physician specialty on guideline
      adherence, the primary outcome. Secondary outcome measures were variability in
      evaluation among physician specialists, and the proportion of patients developing
      urologic cancer. RESULTS: Only 36 of 100 patients had a guideline-adherent
      evaluation, of which 5 were diagnosed with urologic cancer (median 1 month, range
      0-11). No urologic cancers were diagnosed in 64 patients with nonadherent
      evaluations. Only evaluation by a urologist significantly predicted guideline
      adherence (P <.0001). Patients with gross hematuria more often underwent
      intravenous or computed tomography urography (P = .009); urologist evaluation
      more often led to intravenous or computed tomography urography (P <.0001),
      cystoscopy (P <.0001), cytology (P = .009), and guideline-adherent evaluation (P
      <.0001). CONCLUSIONS: Although most physicians did not adhere to 2001 AUA
      guidelines when evaluating patients with asymptomatic hematuria, no urologic
      cancers were diagnosed in patients without guideline-adherent evaluation, barring
      the possibility of occult cancers. Evaluation by a urologist was the only
      predictor of a guideline-adherent evaluation. Future studies are needed to
      determine the optimal evaluation of patients with asymptomatic hematuria.

PMID- 24565589
TI  - Hantavirus infections among overnight visitors to Yosemite National Park,
      California, USA, 2012.
AB  - In summer 2012, an outbreak of hantavirus infections occurred among overnight
      visitors to Yosemite National Park in California, USA. An investigation
      encompassing clinical, epidemiologic, laboratory, and environmental factors
      identified 10 cases among residents of 3 states. Eight case-patients experienced
      hantavirus pulmonary syndrome, of whom 5 required intensive care with ventilatory
      support and 3 died. Staying overnight in a signature tent cabin (9 case-patients)
      was significantly associated with becoming infected with hantavirus (p<0.001).
      Rodent nests and tunnels were observed in the foam insulation of the cabin walls.
      Rodent trapping in the implicated area resulted in high trap success rate (51%),
      and antibodies reactive to Sin Nombre virus were detected in 10 (14%) of 73
      captured deer mice. All signature tent cabins were closed and subsequently
      dismantled. Continuous public awareness and rodent control and exclusion are key
      measures in minimizing the risk for hantavirus infection in areas inhabited by
      deer mice. 

PMID- 24565591
TI  - Remote ischemic preconditioning and endothelial function in patients with acute
      myocardial infarction and primary PCI.
AB  - BACKGROUND: Remote ischemic preconditioning by transient limb ischemia reduces
      myocardial ischemia-reperfusion injury in patients undergoing percutaneous
      coronary intervention. The aim of the study we report here was to assess the
      effect of remote ischemic preconditioning on endothelial function in patients
      with acute myocardial infarction who underwent primary percutaneous coronary
      intervention. METHODS: Forty-eight patients with acute myocardial infarction were
      enrolled. All participants were randomly divided into 2 groups. In Group I (n =
      23), remote ischemic preconditioning was performed before primary percutaneous
      coronary intervention (intermittent arm ischemia-reperfusion through 4 cycles of
      5-minute inflation and 5-minute deflation of a blood-pressure cuff to 200 mm Hg).
      In Group II (n = 25), standard percutaneous coronary intervention without
      preconditioning was performed. We assessed endothelial function using the flow
      mediated dilation test on baseline, then within 1-3 hours after percutaneous
      coronary intervention, and again on days 2 and 7 after percutaneous coronary
      intervention. RESULTS: The brachial artery flow-mediated dilation results were
      significantly higher on the first day after primary percutaneous coronary
      intervention in the preconditioning group (Group I) than in the control group
      (Group II) (12.1% vs 0.0%, P = .03, and 11.1% vs 6.3%, P = .016, respectively),
      and this difference remained on the seventh day (12.3% vs 7.4%, P = .0005,
      respectively). CONCLUSION: We demonstrated for the first time that remote
      ischemic preconditioning before primary percutaneous coronary intervention
      significantly improves endothelial function in patients with acute myocardial
      infarction, and this effect remains constant for at least a week. We suppose that
      the improvement of endothelial function may be one of the possible explanations
      of the effect of remote ischemic preconditioning.

PMID- 24565592
TI  - Intravenous beta agonists and severe pediatric asthma exacerbation: time for a
      closer look at terbutaline?

PMID- 24565593
TI  - Effect of maternal omega3 fatty acid supplementation on infant allergy.

PMID- 24565594
TI  - T-cell biology in immunotherapy.
AB  - OBJECTIVE: This review discusses the current state of immunotherapy and how the
      CD4 T-cell response is pivotal in altering the allergic response. DATA SOURCES:
      PubMed literature review. STUDY SELECTIONS: Articles pertaining to subcutaneous,
      sublingual, and oral immunotherapies, with specific emphasis on those describing
      the T-cell response. RESULTS: Although many drugs are available that help
      ameliorate allergic symptoms, the only intervention that has proved to provide
      long-term benefit and modulation of disease is immunotherapy. Many routes of
      immunotherapy are being pursued, including subcutaneous, sublingual, and oral
      immunotherapies; however, subcutaneous immunotherapy has the historical record of
      leading to immune changes that alter the immune response at subsequent allergen
      exposure. These changes are mediated by the induction of peripherally derived T
      regulatory cells and appear to occur only after high-dose therapy for 3 to 5
      years. Newer methods of sublingual and oral immunotherapies are currently being
      investigated, but their efficacy is not yet on par with subcutaneous
      immunotherapy. CONCLUSION: The primary cells ultimately responsible for
      successful immunomodulation are CD4 T cells, specifically peripherally derived T
      regulatory cells.

PMID- 24565595
TI  - Long-term follow-up of IgE-mediated food allergy: determining persistence versus
      clinical tolerance.

PMID- 24565596
TI  - Lymphopenia induced by etanercept.

PMID- 24565597
TI  - Acquired C1 inhibitor deficiency: should we monitor for associated antibody
      deficiency?

PMID- 24565598
TI  - Radiocontrast-induced iodide sialadenopathy and neutrophilic dermatosis.

PMID- 24565599
TI  - On the cover-green ash.

PMID- 24565600
TI  - Initial characteristics and outcome of hospitalized patients with amiodarone
      pulmonary toxicity.
AB  - Amiodarone-induced pulmonary toxicity (APT) is a serious adverse event that can
      lead to death. The aims of our study are to determine factors associated with
      mortality and to describe outcome and sequelae of patients with APT. METHODS:
      Forty-six patients with APT were divided into two groups according to survival at
      day 90 for a clinical, functional, biological and radiological comparaison. We
      then evaluated the evolution of 15 survivors at a median of three months [1-6
      months] and/or 12 months [8-36 months]. RESULTS: Mortality of APT at day 90 was
      37% (17 patients) and was linked to the speed of onset of symptoms and a high
      HRCT alveolar score. Angiotensin system antagonist treatment was prescribed
      significantly more in the survival group (p = 0.042, HR 0.34 (95% CI 0.12-0.96)).
      In surviving patients, dyspnea, vital capacity and HRCT alveolar score improved
      significantly while HRCT fibrosis score deteriorated gradually during the first
      six months. At the end of the study, all the surviving patients presented
      functional and/or radiological sequelae. CONCLUSIONS: Severity of APT is linked
      to the extent and speed of onset of pulmonary damage. After the initial episode,
      the patients who survived improved slowly but with persistent sequelae.

PMID- 24565601
TI  - Observational study in severe asthmatic patients after discontinuation of
      omalizumab for good asthma control.
AB  - INTRODUCTION: Severe persistent asthma represents a major and costly public
      health issue. There is evidence that long-term treatment with omalizumab might
      have disease-modifying activity but data on the consequences of discontinuing
      treatment after a positive response are limited. The purpose of this study was to
      investigate-in real-life prescribing conditions-what happens when omalizumab is
      discontinued in patients with severe, persistent allergic asthma who have
      responded well to omalizumab treatment. METHODS: An observational, descriptive,
      cross-sectional, retrospective study to establish the time to loss of asthma
      control after the discontinuation of courses of omalizumab treatment of varying
      duration. RESULTS: 24 lung specialists reviewed data from 61 responder patients
      who had discontinued omalizumab after a mean duration of 22.7 +/- 13.1 [range:
      2.5; 59.5] months of treatment. Loss of asthma control was documented in 34
      patients (55.7%) with a median interval between discontinuation and loss of
      control of 13.0 months (mean 20.4 +/- 2.6 [95% CI: 8.3-28.1]). No correlation was
      detected between time to loss of control and duration of treatment, although
      control tended to be sustained for longer in patients whose response had been
      classified as "excellent" as opposed to "good" (median: 17.0 vs. 12.8 months;
      NS). DISCUSSION: The discontinuation of omalizumab was not associated with any
      rebound effect or exacerbation of the disease, and control was sustained
      throughout the follow-up period of at least 6 months in nearly half of all
      patients, including all of those who had been treated for 3.5 years or more.
      After the reintroduction of omalizumab, 4 out of 20 patients did not respond
      again.

PMID- 24565602
TI  - Determinants of exercise capacity in obese and non-obese COPD patients.
AB  - BACKGROUND: The effects of obesity in combination with chronic obstructive
      pulmonary disease (COPD) on exercise capacity are receiving increased attention.
      But, a comprehensive analysis of factors associated with aerobic capacity in
      obese COPD patients has not been performed. METHODS: Six-min walking test (6MWT)
      was performed in 251 COPD patients, and 159 of those also carried out an
      incremental cardiopulmonary exercise test (CPET) to evaluate exercise capacity.
      In all patients, anthropometrics, dyspnea and anxiety-depression scores, lung
      function, daily physical activity, co-morbidities and circulating inflammatory
      biomarkers were also assessed. Six-min walking distance (6MWD) and peak oxygen
      uptake (VO2 peak) during CPET were two primary outcome variables. RESULTS: 57% of
      the patients showed body mass index (BMI) < 30 kg/m2 (COPDN) and the remaining
      43% were obese with a BMI >= 30 kg/m2 (COPDO). In patients with COPDN, 6MWD
      showed independent negative associations with age, dyspnea score, sedentarism,
      depression scores and a positive relationship with arterial oxygenation; whereas
      in COPDO, 6MWD showed an inverse relationship with BMI. In COPDN, VO2 peak showed
      a negative association with age and positive relationships with both FEV1 and
      DLCO. However, in COPDO the dyspnea score was the strongest determinant of VO2
      peak. CONCLUSIONS: Obese and non-obese COPD patients show different determinants
      of aerobic capacity, including pulmonary and non-pulmonary factors that are also
      dependent on the type of exercise protocol. These results could be considered in
      the evaluation of obese patients with COPD.

PMID- 24565603
TI  - Neurofibromatosis type I with breast cancer: not only for women!
AB  - The association of neurofibromatosis type I with invasive male breast cancer is a
      rare clinical entity with only one case in literature reported in 1953. Women
      with NF1 are at risk of developing breast cancer and men also may be at risk but
      there is scarce data on the risk and association of NF1 with male breast cancer
      due to its rarity. Established clinical trials in male breast cancer patients are
      lacking and the results are extrapolated from female breast cancer patients. The
      treatment of male breast cancer is followed as per the guidelines of
      premenopausal female breast cancer and tamoxifen is the hormone treatment in
      them. Mendes et al suggests that silencing of NF1 gene confers resistance to
      tamoxifen. Our conclusions are that since NF1 is mutated or deleted in one third
      of sporadic breast cancers, its role as a molecular driver for treatment has to
      be further explored. 

PMID- 24565604
TI  - [Cost-per-responder analysis comparing romiplostim to rituximab in the treatment
      of adult primary immune thrombocytopenia in Spain].
AB  - BACKGROUND AND OBJECTIVE: Romiplostim, a thrombopoietin-receptor agonist, is
      approved for second-line use in idiopathic thrombocytopenic purpura (ITP)
      patients where surgery is contraindicated. Anti-CD20 rituximab, an
      immunosuppressant, is currently used off-label. This analysis compared the cost
      per responder for romiplostim versus rituximab in Spain. MATERIALS AND METHOD: A
      decision analytic model was constructed to estimate the 6-month cost per
      responding patient (achieving a platelet count>=50*10(9)/l) according to the most
      robust published data. A systematic literature review was performed to extract
      response rates from phase 3 randomized controlled trials. Romiplostim patients
      received weekly injections; rituximab patients received 4 weekly intravenous
      infusions. Medical resource costs were obtained from Spanish reimbursement lists.
      Treatment non-responders incurred bleeding-related event (BRE) management costs
      as reported in clinical trials. Medical resource utilization and clinical
      practice were based on Spanish treatment guidelines and validated by local
      clinical experts. RESULTS: The literature review identified phase 3 romiplostim
      trials with a response rate of 83%. Due to a lack of phase 3 controlled rituximab
      trials, a systematic review of studies was selected as the best source, reporting
      a response rate of 62.5%. The mean cost per patient for romiplostim was ?16,289
      and ?13,459 for rituximab. Rituximab resulted in a 10% higher cost per responder
      (?21,535 versus ?19,625 for romiplostim). Romiplostim use reduced drug
      administration, intravenous immunoglobulin, and bleeding-related costs compared
      to rituximab. CONCLUSIONS: Due to its high level of efficacy leading to lower BRE
      costs, romiplostim represents an efficient use of resources for adult ITP
      patients in the Spanish Healthcare System.

PMID- 24565605
TI  - Relative validity of micronutrient and fiber intake assessed with two new
      interactive meal- and Web-based food frequency questionnaires.
AB  - BACKGROUND: The meal- and Web-based food frequency questionnaires, Meal-Q and
      MiniMeal-Q, were developed for cost-efficient assessment of dietary intake in
      epidemiological studies. OBJECTIVE: The objective of this study was to evaluate
      the relative validity of micronutrient and fiber intake assessed with Meal-Q and
      MiniMeal-Q. The reproducibility of Meal-Q was also evaluated. METHODS: A total of
      163 volunteer men and women aged between 20 and 63 years were recruited from
      Stockholm County, Sweden. Assessment of micronutrient and fiber intake with the
      174-item Meal-Q was compared to a Web-based 7-day weighed food record (WFR). Two
      administered Meal-Q questionnaires were compared for reproducibility. The 126
      item MiniMeal-Q, developed after the validation study, was evaluated in a
      simulated validation by using truncated Meal-Q data. RESULTS: The study
      population consisted of approximately 80% women (129/163) with a mean age of 33
      years (SD 12) who were highly educated (130/163, 80% with >12 years of education)
      on average. Cross-classification of quartiles with the WFR placed 69% to 90% in
      the same/adjacent quartile for Meal-Q and 67% to 89% for MiniMeal-Q. Bland-Altman
      plots with the WFR and the questionnaires showed large variances and a trend of
      increasing underestimation with increasing intakes. Deattenuated and energy
      adjusted Spearman rank correlations between the questionnaires and the WFR were
      in the range rho=.25-.69, excluding sodium that was not statistically
      significant. Cross-classifications of quartiles of the 2 Meal-Q administrations
      placed 86% to 97% in the same/adjacent quartile. Intraclass correlation
      coefficients for energy-adjusted intakes were in the range of .50-.76.
      CONCLUSIONS: With the exception of sodium, this validation study demonstrates
      Meal-Q and MiniMeal-Q to be useful methods for ranking micronutrient and fiber
      intake in epidemiological studies with Web-based data collection.

PMID- 24565607
TI  - A case of Kawasaki's disease with extensive calcifications needing rotational
      atherectomy with a 2.5mm burr.
AB  - This case report demonstrates a unique strategy requiring a 2.5 mm burr to treat
      in-stent restenosis of an originally underexpanded stent, implanted in a heavily
      calcified lesion within a giant aneurysm by Kawasaki disease. Despite our
      procedural success, it should be emphasized that stent implantation in
      undilatable lesions should be avoided. When an angiographically calcified lesion
      within an ectatic segment is observed in a patient with Kawasaki disease, it is
      recommended that the operator evaluates in detail the severity and location of
      calcification using intravascular ultrasound imaging and pays meticulous
      attention to lesion preparation.

PMID- 24565606
TI  - Semi-quantitative analysis of changes in the plasma peptidome of Manduca sexta
      larvae and their correlation with the transcriptome variations upon immune
      challenge.
AB  - The tobacco hornworm, Manduca sexta, has been used as a biochemical model for
      studying insect physiological processes. While the transcriptomes of its fat
      body, hemocytes, midgut, and antennae have been examined in several studies,
      limited information is available for proteins in tissues, cells, or body fluids
      of this insect. In keeping pace with the M. sexta genome project, we launched a
      pilot study to identify differences in the peptidome of cell-free hemolymph
      samples from larvae injected with buffer or a mixture of bacteria. At 24 h after
      injection, plasma was collected and treated with 50% acetonitrile to precipitate
      large proteins. The supernatants, containing peptides (<25 kDa) and other stable
      proteins (>25 kDa), were digested with trypsin and analyzed by nano-liquid
      chromatography and nano-electrospray tandem mass spectrometry (nanoLC-MS/MS) on
      an LTQ Orbitrap XL mass spectrometer. Known M. sexta cDNA sequences and gene
      transcripts from the draft genome were translated in silico to generate a
      database of polypeptides (i.e. peptides and proteins) in this species. By
      searching the database, we identified 268 hemolymph polypeptides, 50 of which
      showed 1.67-200 fold abundance increases after the immune challenge, as judged by
      significant changes in normalized spectral counts between the control and induced
      plasma. These included a total of 33 antimicrobial peptides (attacins, cecropins,
      defensins, diapausins, gallerimycin, gloverin, lebocins, lysozymes), pattern
      recognition receptors, and proteinase inhibitors. Although there was no strong
      parallel (correlation coefficients: -0.13, 0.11, 0.39 and 0.62) between plasma
      peptide levels and their transcript levels in control or induced hemocytes or fat
      body, we observed the mRNA level changes in hemocytes and fat body concurred with
      their peptide level changes with correlation coefficients of 0.67 and 0.76,
      respectively. These data suggest that fat body contributed a significant portion
      of the plasma polypeptides involved in various aspects of innate immunity after
      the bacterial injection. 

PMID- 24565608
TI  - 2nd Congress on applied synthetic biology in Europe (Malaga, Spain, November
      2013).
AB  - The second meeting organised by the EFB on the advances of applied synthetic
      biology in Europe was held in Malaga, Spain in November 2013. The potential for
      the broad application of synthetic biology was reflected in the five sessions of
      this meeting: synthetic biology for healthcare applications, tools and
      technologies for synthetic biology, production of recombinant proteins, synthetic
      plant biology, and biofuels and other small molecules. Outcomes from the meeting
      were that synthetic biology offers methods for rapid development of new strains
      that will result in decreased production costs, sustainable chemical production
      and new medical applications. Additionally, it also introduced novel ways to
      produce sustainable energy and biofuels, to find new alternatives for
      bioremediation and resource recovery, and environmentally friendly foodstuff
      production. All the above-mentioned advances could enable biotechnology to solve
      some of the major problems of Society. However, while there are still limitations
      in terms of lacking tools, standardisation and suitable host organisms, this
      meeting has laid a foundation providing cutting-edge concepts and techniques to
      ultimately convert the potential of synthetic biology into practice. 

PMID- 24565609
TI  - Development of an improved variant of GH51 alpha-l-arabinofuranosidase from
      Pleurotus ostreatus by directed evolution.
AB  - In this study, the alpha-l-arabinofuranosidase from Pleurotus ostreatus was
      subjected to directed evolution by expressing a library of around 7000 randomly
      mutated variants by error prone Polymerase Chain Reaction. High-throughput
      screening of the library for the most active variants was performed by assaying
      activity towards p-nitrophenyl alpha-l-arabinofuranoside, and a variant with
      higher activity than the wild type was selected, purified and characterised. It
      exhibited a kcat of 7.3 *1 01 +/- 0.3 min-1, around 3-fold higher than that of
      the wild type (2.2 * 103 +/- 0.2 min-1), and a KM (0.54 +/- 0.0 6mM) 30% lower
      than that of the wild type (0.70 +/- 0.05 mM) towards this substrate. The mutant
      also showed improved catalytic properties towards pNP-beta-d-glucopyranoside
      (kcat of 50.85 +/- 0.21 min-1 versus 11.0 +/- 0.6 min-1) and it was shown able to
      hydrolyse larch arabinogalactan which is not recognised by the wild type. The
      mutant was also more active than the wild type towards arabinoxylan and was able
      to hydrolyse arabinan, which was not transformed by the wild type. The ability of
      rPoAbf F435Y/Y446F to hydrolyse these insoluble substrates expands its potential
      for application also to hemicelluloses, which in some types of pretreatment are
      recovered in solid fractions.

PMID- 24565610
TI  - Buruli ulcer in Liberia, 2012.

PMID- 24565611
TI  - Bringing your "A" game to urticaria and angioedema.

PMID- 24565612
TI  - Hereditary angioedema with normal C1-INH (HAE type III).
AB  - Hereditary angioedema (HAE) with normal C1 inhibitor (C1-INH), also known as HAE
      type III, is a familial condition only clinically recognized within the past
      three decades. Similar to HAE from C1-INH deficiency (HAE types I and II),
      affected individuals experience unpredictable angioedema episodes of the skin,
      gastrointestinal tract, and airway. Unique clinical features of HAE with normal
      C1-INH include the predominance of affected women, frequent exacerbation by
      estrogen, and a prominence of angioedema that involves the face and oropharynx.
      The underlying pathophysiology of HAE with normal C1-INH is poorly understood,
      but indirect evidence points to contact pathway dysregulation with bradykinin
      mediated angioedema. Currently, evaluation is complicated by a lack of
      confirmatory laboratory testing such that clinical criteria must often be used to
      make the diagnosis of HAE with normal C1-INH. Factor XII mutations have been
      identified in only a minority of persons affected by HAE with normal C1-INH,
      limiting the utility of such analysis. To date, no controlled clinical studies
      have examined the efficacy of therapeutic agents for HAE with normal C1-INH,
      although published evidence supports frequent clinical benefit with medications
      shown effective in HAE due to C1-INH deficiency. 

PMID- 24565613
TI  - Alternative agents in refractory chronic urticaria: evidence and considerations
      on their selection and use.
AB  - Patients with chronic urticaria (CU) who are refractory to antihistamines are
      frequently encountered by allergy specialists. Several alternative agents have
      been used to treat these patients; however, the evidence to support these agents
      is generally limited. This review focuses on some of the more commonly used
      alternative agents in refractory CU, including anti-inflammatory agents
      (montelukast, hydroxychloroquine, dapsone, sulfasalazine, methotrexate,
      colchicine), immunosuppressants (cyclosporine, tacrolimus, mycophenolate), and
      immunomodulatory agents (omalizumab, immune globulin). The evidence to support
      their use, dosing, potential toxicity, monitoring, and selection of these
      alternative agents is reviewed. Although numerous knowledge gaps exist for
      alternative agents in refractory CU, a rational, patient-based approach can be
      used with a goal of improving control and quality of life and minimizing adverse
      medication effects. 

PMID- 24565614
TI  - ACE inhibitor-induced angioedema.
AB  - Angiotensin-converting enzyme inhibitors (ACEI) are commonly prescribed for blood
      pressure control and renal protection. ACEI angioedema is a common problem in
      patients who are taking ACEI, although, in most cases, the disorder is self
      limited, and spontaneous episodes of apparently unprovoked angioedema stop with
      the discontinuation of the medication. In a subset of patients, hospitalization
      and even intubation are required for airway protection. The diagnosis is made
      clinically. There are no laboratory studies that establish the diagnosis.
      However, such investigations help exclude alternative diagnoses as the cause for
      the patient's presentation. Conventional treatment with regimens used to control
      allergic angioedema is ineffective in this condition. The mechanism of ACEI
      induced angioedema is thought to be related to its effect on the kallikrein-kinin
      system. Kallikrein is a protease that converts high-molecular-weight kininogens
      into kinins, primarily bradykinin. Medications recently developed, primarily
      icatibant and ecallantide, to control hereditary angioedema, a disorder also
      associated with kallikrein-kinin activation, have been used to treat ACEI
      angioedema with some success. The efficacy of these agents and their optimal use
      remains to be established by randomized and placebo controlled trials. 

PMID- 24565615
TI  - Adherence monitoring and e-health: how clinicians and researchers can use
      technology to promote inhaler adherence for asthma.
AB  - In the past decade, rapid technological developments have advanced electronic
      monitoring devices (EMD) for asthma inhalers beyond simple recording of
      actuations to providing adherence promotion features and detailed information
      about patterns of medication use. This article describes currently available
      EMDs, discusses their utility and limitations in assessing adherence, and
      describes the potential for EMD-based adherence promotion interventions in
      clinical settings. To date, the main use of EMDs has been in clinical research.
      In selected populations, simple EMD-based adherence interventions, delivered
      either through clinician-to-patient feedback about medication use or by direct-to
      patient reminders for missed doses, can significantly improve adherence. Further
      work is now needed to determine the impact of EMDs on clinical outcomes and their
      cost-effectiveness and feasibility for different clinical settings, including in
      disadvantaged populations. If this evidence can be provided, then the use of EMDs
      could expand into the management of asthma in populations with high health care
      costs, eg, severe asthma. In the future, medication monitoring could help
      distinguish poor treatment response from poor adherence, guide prescribing
      decisions, and prompt providers to discuss barriers to adherence; electronic
      health records may provide the gateway for integrating medication-use monitoring
      into digital chronic care management. 

PMID- 24565616
TI  - Allergy immunotherapy safety: location matters!
AB  - Allergy immunotherapy is a highly effective therapy that has been used in the
      treatment of allergic rhinitis, asthma, and venom allergy for over a century.
      Subcutaneous immunotherapy (SCIT) is currently the only US Food and Drug
      Administration approved form of allergy immunotherapy. In this commentary, we
      address the safety issues that surround the location of care of SCIT
      administration in a supervised medical facility versus in the home or other
      medically unsupervised facility. Although analysis of the data suggests that SCIT
      has an excellent safety profile, we believe that this safety is largely due to
      the safety measures that are implemented when SCIT is administered in a medically
      supervised setting with appropriate staff and equipment to immediately recognize
      and treat anaphylaxis. In the home or medically unsupervised setting, the
      preinjection health assessment may not be adequate and access to immediate
      emergency medical treatment is unlikely to occur. We strongly urge all health
      care providers to adhere to the current Allergy Immunotherapy Practice Parameter
      recommendations and that patients be appropriately assessed before and monitored
      after allergy immunotherapy injections in a medically supervised facility. 

PMID- 24565617
TI  - US Hereditary Angioedema Association Medical Advisory Board 2013 recommendations
      for the management of hereditary angioedema due to C1 inhibitor deficiency.
AB  - BACKGROUND: The treatment of hereditary angioedema (HAE) has undergone dramatic
      changes as newer medicines have become available in recent years. Optimal care of
      these patients requires a comprehensive management plan. Although several
      consensus papers have been published concerning the diagnosis and treatment of
      HAE, guidelines for a comprehensive management plan have not been developed.
      OBJECTIVE: To develop state-of-the-art recommendations for the treatment and
      management of HAE due to C1 inhibitor (C1INH) deficiency in the United States.
      METHODS: Members of the US Hereditary Angioedema Association Medical Advisory
      Board began by reviewing the literature concerning treatment of HAE. Preliminary
      recommendations were developed based on the literature review, discussions in a
      face-to-face meeting, and refinements in a series of drafts. Final
      recommendations reflect the unanimous consensus of the medical advisory board and
      the US Hereditary Angioedema Association leadership. RESULTS: Recommendations are
      provided regarding a comprehensive care plan for HAE, including the following:
      development of an overall management plan, treatment of angioedema attacks,
      prophylactic treatment, and patient monitoring. CONCLUSION: A comprehensive
      individualized management plan developed between an expert HAE physician and the
      patient, in collaboration with local medical providers and emergency departments,
      can provide patients with the best opportunity to lead a normal life.

PMID- 24565618
TI  - Pollen count and presentation of angiotensin-converting enzyme inhibitor
      associated angioedema.
AB  - BACKGROUND: The incidence of angiotensin-converting enzyme (ACE) inhibitor
      associated angioedema is increased in patients with seasonal allergies.
      OBJECTIVE: We tested the hypothesis that patients with ACE inhibitor-associated
      angioedema present during months when pollen counts are increased. METHODS:
      Cohort analysis examined the month of presentation of ACE inhibitor-associated
      angioedema and pollen counts in the ambulatory and hospital setting. Patients
      with ACE inhibitor-associated angioedema were ascertained through (1) an
      observational study of patients presenting to Vanderbilt University Medical
      Center, (2) patients presenting to the Marshfield Clinic and participating in the
      Marshfield Clinic Personalized Medicine Research Project, and (3) patients
      enrolled in The Ongoing Telmisartan Alone and in Combination with Ramipril Global
      Endpoint Trial (ONTARGET). Measurements include date of presentation of ACE
      inhibitor-associated angioedema, population exposure to ACE inhibitor by date,
      and local pollen counts by date. RESULTS: At Vanderbilt, the rate of angioedema
      was significantly associated with tree pollen months (P = .01 from chi(2) test).
      When separate analyses were conducted in patients with a history of seasonal
      allergies and patients without, the rate of ACE inhibitor-associated angioedema
      was increased during tree pollen months only in patients with a history of
      seasonal allergies (P = .002). In Marshfield, the rate of angioedema was
      significantly associated with ragweed pollen months (P = .025). In ONTARGET, a
      positive trend was observed between the ACE inhibitor-associated angioedema rate
      and grass season, although it was not statistically significant (P = .057).
      CONCLUSIONS: Patients with ACE inhibitor-associated angioedema are more likely to
      present with this adverse drug event during months when pollen counts are
      increased.

PMID- 24565619
TI  - Venom immunotherapy in patients with clonal mast cell disorders: efficacy,
      safety, and practical considerations.
AB  - BACKGROUND: A preferential association between systemic mastocytosis (SM) and
      hymenoptera allergy (HVA) has been observed. Patients with both diseases are at
      risk for more severe reactions, and venom immunotherapy (VIT) may represent a
      life-saving treatment, but the use of VIT in such patients raised concerns about
      its safety. OBJECTIVE: We evaluated a large population of patients with SM and
      HVA who received VIT. METHODS: This prospective study was performed in Italy and
      Spain. A diagnosis of SM and HVA and a VIT prescription were made according to
      international recommendations. The patients were carefully followed up during
      VIT, with special attention to field stings. RESULTS: A total of 84 patients (70
      men, 14 women; mean age 52.1 years) were included, 81% with grade IV reaction,
      91% with indolent SM. No difference was seen between the Italian and Spanish
      patients. There were 10 adverse reactions during the induction phase: 3 with the
      conventional induction and 7 with the rush-modified induction, none resulted in
      epinephrine administration and/or hospitalization. Fifty patients had one or more
      field re-sting (95 episodes), none during induction. The time elapsed from
      starting VIT and first re-sting was 2 months to 7 years, and the number of re
      stings per patient was 1-6. Of the 50 patients who were re-stung, 43 (86%)
      resulted in being fully protected. Seven patients had reactions, and the
      maintenance dose was safely increased to 200 mcg. The maintenance dose interval
      was not different between patients with and those without reactions at re-stings.
      CONCLUSION: VIT is well tolerated, safe, and effective in patients with SM.

PMID- 24565621
TI  - Carboplatin-, oxaliplatin-, and cisplatin-specific IgE: cross-reactivity and
      value in the diagnosis of carboplatin and oxaliplatin allergy.
AB  - BACKGROUND: The diagnosis of hypersensitivity reactions (HSR) to platins is based
      on the characterization of the reaction and the results of skin testing. Platins
      can be irritants when used in skin testing; therefore, in vitro testing may offer
      an alternative diagnostic tool. OBJECTIVE: To evaluate sensitivity and
      specificity of platin specific IgE (sIgE) in patients with HSRs and in controls.
      METHODS: Twenty-four patients with immediate HSR to platins were included
      (carboplatin, 12; oxaliplatin, 12): 19 women and 5 men (mean age, 61 years). The
      control group included 17 patients exposed to platin and with no HSR. Skin
      testing was performed on 22 patients. Carboplatin sIgE and oxaliplatin sIgE were
      measured in 24 patients and 17 controls; carboplatin sIgE was measured in 21
      patients. RESULTS: Skin test results were positive in 22 patients (carboplatin,
      12/12; oxaliplatin, 10/12). Seven of 12 patients sensitive to carboplatin (59%)
      had positive carboplatin sIgE, 2 also had positive cisplatin sIgE, and all had
      negative oxaliplatin sIgE; 9 of 12 patients sensitive to oxaliplatin (75%) had
      positive sIgE to oxaliplatin, 8 of 12 (67%) also had positive carboplatin and
      cisplatin sIgE, to which they had not been exposed. All 5 carboplatin controls
      had negative sIgE; 3 oxaliplatin controls (25%) had positive carboplatin sIgE,
      and 2 had positive oxaliplatin sIgE. CONCLUSION: Carboplatin sIgE is very
      specific but less sensitive. In contrast, oxaliplatin sIgE had higher sensitivity
      but lower specificity. Analysis of our data suggests that oxaliplatin exposure
      was more immunogenic. This could be clinically relevant because patients
      sensitized to carboplatin may be able to tolerate oxaliplatin, but patients
      sensitized to oxaliplatin may be at risk when exposed to carboplatin and
      cisplatin.

PMID- 24565620
TI  - The impact of peer support and mp3 messaging on adherence to inhaled
      corticosteroids in minority adolescents with asthma: a randomized, controlled
      trial.
AB  - BACKGROUND: Poor adherence to inhaled corticosteroids (ICS) is a critical risk
      factor contributing to asthma morbidity among low-income minority adolescents.
      OBJECTIVE: This trial tested whether peer support group meetings and peer asthma
      messages delivered via mp3 players improved adherence to ICS. METHODS: Low-income
      African American and/or Hispanic adolescents, ages 11-16 years old, with
      persistent asthma, and poor (<= 48%) adherence to prescription ICS during the 3
      week run-in were randomized to intervention or attention control groups (ATG) for
      the 10-week treatment. During treatment, the intervention arm subjects
      participated in weekly coping peer group support sessions and received mp3 peer
      recorded asthma messages that promoted adherence. The ATG participated in weekly
      meetings with a research assistant and received an equivalent number of mp3
      physician-recorded asthma messages. Adherence was measured by using self-report
      and the Doser CT, an electronic dose counter. The primary outcome was the
      difference in adherence at 10 weeks between the 2 arms. RESULTS: Thirty-four
      subjects were randomized to each arm. At 10 weeks, no statistical difference in
      objectively measured adherence could be detected between the 2 arms when
      adjusting for baseline adherence (P = .929). Adherence declined in both groups
      over the course of the active treatment period. In both study arms, self-reported
      adherence by participants was significantly higher than their objectively
      measured adherence at week 10 (P < .0001). CONCLUSION: Improving medication
      adherence in longitudinal studies is challenging. Peer support and mp3-delivered
      peer asthma messages may not be of sufficient dose to improve outcomes.

PMID- 24565622
TI  - The relationship between a specific IgE level and asthma outcomes: results from
      the 2005-2006 National Health and Nutrition Examination Survey.
AB  - BACKGROUND: Allergen exposure is associated with increased specific IgE (sIgE),
      and allergen exposure plus sensitization is predictive of asthma outcomes.
      However, it is not known if sIgE is predictive of asthma outcomes in the absence
      of exposure data. OBJECTIVE: To investigate whether IgE to indoor allergens is
      predictive of and has a dose-response relationship with asthma emergency
      department (ED) visits and wheeze. METHODS: In the 2005-2006 National Health and
      Nutrition Examination Survey, 351 children and 390 adults reported current
      asthma. Continuous sIgE to 9 indoor allergens were considered. Asthma morbidity
      in the past year was measured by wheezing. Health care utilization was defined as
      any asthma ED visits in the past year. RESULTS: Analyses were adjusted for race,
      age, education, poverty index ratio and (in adults) tobacco use. In children, ED
      visits were associated with cockroach (odds ratio [OR] 1.5 [95% CI, 1.1-2 .1),
      rat (OR 1.9 [95% CI, 1.2-2.8]), and Aspergillus (OR 1.6 [95% CI, 1.001-2.60]).
      Continuous Aspergillus (OR 1.5 [95% CI, 1.04-2.1), Alternaria (OR 1.4 [95% CI,
      1.1-1.6]), and total IgE (OR 1.2 [95% CI, 1.1-1.4]) were associated with wheeze
      in children. Adult ED visits were associated with sIgE for dust mites
      (Dermatophagoides pteronyssinus OR 1.6 [95% CI, 1.3-2.1]; Dermatophagoides
      farinae OR 1.6 [95% CI, 1.3-1.9]), total IgE (OR 1.4 [95% CI, 1.04- 1.9]), and
      the sum of sIgEs (OR 1.6 [95% CI, 1.2-2.2]). CONCLUSIONS: Sensitization to
      particular indoor environmental allergens was found to be a risk factor for
      wheeze and asthma ED visits. These outcomes increased as the concentration of
      sIgE to these allergens increased.

PMID- 24565624
TI  - Raising the bar for asthma care in the emergency department.

PMID- 24565625
TI  - Case of recurrent exophthalmos: angioedema versus idiopathic orbital pseudotumor.

PMID- 24565623
TI  - Quality of care for acute asthma in emergency departments in Japan: a multicenter
      observational study.
AB  - BACKGROUND: Little is known about the quality of acute asthma care in emergency
      departments (EDs) outside of North America. OBJECTIVE: We evaluated concordance
      of acute asthma management in Japanese EDs with recommendations in the 2007
      National Institutes of Health asthma guidelines and investigated whether
      guideline concordance was associated with risk of hospital admission. METHODS: We
      conducted a multicenter chart review study in 23 EDs across Japan. We identified
      ED patients aged 18 to 54 years with acute asthma between 2009 and 2011.
      Concordance with evidence-based guideline recommendations was evaluated by using
      item-by-item quality measures and composite concordance scores both at patient
      and ED levels. These scores ranged from 0 to 100. RESULTS: Among 1380 patients,
      the median age was 35 years and 11% were hospitalized. Overall guideline
      concordance score was suboptimal both at the patient level (mean +/- SD, 72 +/-
      14) and ED level (mean +/- SD, 72 +/- 6). Specifically, asthma care at the
      patient level was suboptimal in several areas: inhaled anticholinergics in ED
      (2%), systemic corticosteroid in ED (56%) and at discharge (36%), and peak flow
      assessment (9%). A multivariable model that adjusted for severity at presentation
      and several ED characteristics showed that higher guideline concordance was
      associated with significantly lower risk of hospital admission (odds ratio, 0.70
      per 10-unit increase in composite score; 95% CI, 0.62-0.79 per 10-unit increase
      in composite score). CONCLUSION: The management of acute asthma in Japanese EDs
      is suboptimal. Greater concordance with guideline-recommended management might
      reduce unnecessary hospitalizations. Knowledge translation initiatives are
      warranted to increase adherence with best practice in acute asthma management.

PMID- 24565626
TI  - Urticaria multiforme in an 18-year-old girl.

PMID- 24565627
TI  - Management of chronic idiopathic urticaria in childhood: are we on the same page?

PMID- 24565628
TI  - Implantable venous access device associated complications in patients with
      hereditary angioedema.

PMID- 24565629
TI  - IgE-mediated hypersensitivity to ondansetron and safe use of palonosetron.

PMID- 24565630
TI  - Natural resolution of peanut allergy: a 12-year longitudinal follow-up study.

PMID- 24565631
TI  - Cytokine gene expression profiling to help identify a safe antibiotic in a
      patient with drug rash with eosinophilia and systemic symptoms.

PMID- 24565632
TI  - Increased compound heterozygous filaggrin mutations in severe atopic dermatitis
      in the United States.

PMID- 24565633
TI  - Iatrogenic autoimmune progesterone dermatitis treated with a novel intramuscular
      progesterone desensitization protocol.

PMID- 24565634
TI  - Repeated episodes of anaphylaxis with normal serum tryptase but elevated levels
      of urinary prostaglandin D2.

PMID- 24565635
TI  - Doxycycline or oral corticosteroids for nasal polyps.
AB  - The study by Van Zele et al reports positive results for a randomized, double
      blind, placebo-controlled trial that used either 20 days of doxycycline (200 mg
      the first day, followed by 100 mg daily) or 20 days of a tapering schedule of
      methyl prednisolone (32 mg on days 1-5, 16 mg on days 6-10, and 8 mg on days 11
      20) for the treatment of nasal polyps. The primary end point was reduction in
      nasal polyp score which was graded 0 to 4 on each side, resulting in a score
      range of 0 to 8; the score was determined at baseline and weeks 1, 2, 4, 8, and
      12. Entry criteria required that the patient either have recurrent polyps after
      surgery or massive polyps (grade 3 or 4); the total polyp score in each of the 3
      groups averaged approximately 6. The patient population in this study was
      therefore at the severe end of the spectrum; results may not be generalizable to
      patients with milder disease.

PMID- 24565636
TI  - Re: Integrated research on the association between climate change and Bjerkandera
      allergy.

PMID- 24565637
TI  - Reply: To PMID 23687635.

PMID- 24565640
TI  - Taar1-mediated modulation of presynaptic dopaminergic neurotransmission: role of
      D2 dopamine autoreceptors.
AB  - Trace Amine-Associated Receptor 1 (TAAR1) is a G protein-coupled receptor (GPCR)
      expressed in several mammalian brain areas and activated by "trace amines" (TAs).
      TAs role is unknown; however, discovery of their receptors provided an
      opportunity to investigate their functions. In vivo evidence has indicated an
      inhibitory influence of TAAR1 on dopamine (DA) neurotransmission, presumably via
      modulation of dopamine transporter (DAT) or interaction with the D2 DA receptor
      and/or activation of inwardly rectifying K(+) channels. To elucidate the
      mechanisms of TAAR1-dependent modulation, we used TAAR1 knockout mice (TAAR1-KO),
      a TAAR1 agonist (RO5166017) and a TAAR1 antagonist (EPPTB) in a set of
      neurochemical experiments. Analysis of the tissue content of TAAR1-KO revealed
      increased level of the DA metabolite homovanillic acid (HVA), and in vivo
      microdialysis showed increased extracellular DA in the nucleus accumbens (NAcc)
      of TAAR1-KO. In fast scan cyclic voltammetry (FSCV) experiments, the evoked DA
      release was higher in the TAAR1-KO NAcc. Furthermore, the agonist RO5166017
      induced a decrease in the DA release in wild-type that could be prevented by the
      application of the TAAR1 antagonist EPPTB. No alterations in DA clearance, which
      are mediated by the DAT, were observed. To evaluate the interaction between TAAR1
      and D2 autoreceptors, we tested the autoreceptor-mediated dynamics. Only in wild
      type mice, the TAAR1 agonist was able to potentiate quinpirole-induced inhibitory
      effect on DA release. Furthermore, the short-term plasticity of DA release
      following paired pulses was decreased in TAAR1-KO, indicating less autoinhibition
      of D2 autoreceptors. These observations suggest a close interaction between TAAR1
      and the D2 autoreceptor regulation. 

PMID- 24565641
TI  - GSK-3/CREB pathway involved in the gx-50's effect on Alzheimer's disease.
AB  - Aggregation of amyloid-beta (Abeta) fragments is one of the major pathological
      hallmarks of Alzheimer's disease (AD). Our previous study has demonstrated that a
      novel compound named N-[2-(3, 4-dimethoxyphenyl) ethyl]-3-phenyl-acrylamide (gx
      50) can decrease the accumulation of Abeta oligomers in the cerebral cortex and
      improve the cognitive abilities in transgenic demented mice. To further study the
      mechanism of the neuroprotective effect of gx-50 against AD, we employed
      microarray to investigate the gene expression profile of the primary cultured
      neurons treated with gx-50 or/and Abeta. Microarray disclosed 351 genes
      associated with AD in the gx-50 plus Abeta treated group, out of the 22,523
      probes. 217 of the 351 genes were significantly up-regulated, 134 of them were
      down-regulated. The 351 genes were mainly involved in neurotransmission, signal
      transduction, nervous system development, protein phosphorylation, transcription
      and apoptosis. By the Onto-pathway analysis, a network involved two molecules -
      GSK-3, CREB and another two closely linked proteins - AKT, BDNF was discovered.
      The GSK/CREB pathway was further studied at the gene and protein level both in
      vivo and in vitro. Western blot and immunohistochemistry analysis showed that the
      gx-50 elevated the AKT phosphorylation and inhibited its downstream protein - GSK
      3's activity, then restored the CREB's transcriptional activity, and finally
      enhanced the expression of the CREB target gene - BDNF. In addition, the real
      time PCR results displayed the same tendency. In conclusion, studies in this
      research indicated that the gx-50 may improve the cognitive ability of AD via the
      GSK-3/CREB pathway. 

PMID- 24565642
TI  - Curcumol from Rhizoma Curcumae suppresses epileptic seizure by facilitation of
      GABA(A) receptors.
AB  - Rhizoma Curcumae is a common Chinese dietary spice used in South Asia and China
      for thousands of years. As the main extract, Rhizoma Curcumae oil has attracted a
      great interest due to its newly raised therapeutic activities including its
      pharmacological effects upon central nervous system such as neuroprotection,
      cognitive enhancement, and anti-seizure efficacy; however the molecular
      mechanisms and the target identification remain to be established. Here we
      characterize an inhibitory effect of curcumol, a major bioactive component of
      Rhizoma Curcumae oil, on the excitability of hippocampal neurons in culture, the
      basal locomotor activity of freely moving animals, and the chemically induced
      seizure activity in vivo. Electrophysiological recording showed that acute
      application of curcumol significantly facilitated the gamma-aminobutyric acid
      (GABA)-activated current in cultured mouse hippocampal neurons and in human
      embryonic kidney cells expressing alpha1- or alpha5-containing A type GABA
      (GABAA) receptors in a concentration-dependent manner. Measurement of tonic and
      miniature inhibitory postsynaptic GABAergic currents in hippocampal slices
      indicated that curcumol enhanced both forms of inhibition. In both
      pentylenetetrazole and kainate seizure models, curcumol suppressed epileptic
      activity in mice by prolonging the latency to clonic and tonic seizures and
      reducing the mortality as well as the susceptibility to seizure, presumably by
      facilitating the activation of GABAA receptors. Taken together, our results
      identified curcumol as a novel anti-seizure agent which inhibited neuronal
      excitability through enhancing GABAergic inhibition. 

PMID- 24565644
TI  - HT to HTO conversion and field experiments near Darlington Nuclear Power
      Generating Station (DNPGS) site.
AB  - The Canadian input parameters related to tritiated hydrogen gas (HT) used in
      tritium dose models are currently based on experiments performed at the Chalk
      River Laboratories (CRL) site in 1986, 1987 and 1994. There is uncertainty in how
      well other sites experiencing atmospheric HT releases are represented by these
      data. In order to address this uncertainty, HT to HTO conversion factors were
      evaluated at different locations near the Darlington Nuclear Power Generating
      Station (DNPGS) site using various experimental approaches. These were D2 gas
      exposure chamber experiments, atmospheric tritium measurements, and HTO and OBT
      measurements in vegetation and soil. In addition to these field experiments,
      chamber experiments were conducted using HT gas on field soil samples. The
      suggested Canadian input parameters for atmospheric tritium releases estimate the
      total fraction of HT oxidized in air and in soil, at the site, to be up to a
      maximum of 2.4%. Based on the more limited data obtained near DNPGS in early
      spring, this fraction would likely be closer to 0.5%. The result suggests that
      current parameters provide a conservative estimate for the DNPGS site. 

PMID- 24565643
TI  - Cinnabarinic acid, an endogenous agonist of type-4 metabotropic glutamate
      receptor, suppresses experimental autoimmune encephalomyelitis in mice.
AB  - Cinnabarinic acid (CA) is an endogenous metabolite of the kynurenine pathway
      which acts as an orthosteric agonist of type-4 metabotropic glutamate receptor
      (mGlu4). We now report that systemic administration of CA (0.1-10 mg/kg, i.p.)
      was highly protective against experimental autoimmune encephalomyelitis (EAE)
      induced by the myelin oligodendrocyte glycoprotein (MOG35-55) peptide, which
      models multiple sclerosis in mice. Full protection against EAE required daily
      injections of CA since the time of immunization, similarly to what reported for
      the mGlu4 enhancer N-phenyl-7-(hydroxyimino)cyclopropa[b]chromen-1acarboxamide
      (PHCCC). CA treatment boosted an immune response dominated by regulatory T (Treg)
      cells at the expenses of Th17 cells. In addition, exogenous CA enhanced
      endogenous CA formation in lymphocytes, suggesting the occurrence of a positive
      feedback loop sustaining immune tolerance. To examine whether activation of mGlu4
      could account for the protective activity of CA against EAE, we used mGlu4
      knockout mice. As expected, these mice displayed a more severe form of EAE in
      response to immunization. CA was still protective against EAE in mGlu4-deficient
      mice, although its action was significantly reduced both at high and low CA
      doses. This suggests that the action of CA against neuroinflammation involves
      multiple mechanisms including the activation of mGlu4. These data further suggest
      that CA is one possible bridge between activation of the kynurenine pathway and
      immune tolerance aimed at restraining neuroinflammation. 

PMID- 24565646
TI  - Traumatic injury of the thoracic aorta treated with stent-graft: is long-term CT
      angiography follow-up justified?
AB  - AIM: To report the results of long-term (>5 years) computed tomography (CT)
      angiography follow-up after thoracic endovascular aortic repair in patients with
      traumatic thoracic aortic injury. MATERIALS AND METHODS: All follow-up CT
      angiographies performed in patients with traumatic thoracic aorta injury treated
      by endovascular stent-graft between 2002 and 2008 were reviewed. Of the 14
      patients treated, seven patients had CT angiography follow-up examinations for
      more than 5 years. All patients were men with a mean age of 26 years. The Talent
      device was used in four patients and Gore TAG device in three patients. The mean
      device diameter and length were 24.6 mm and 103 mm, respectively. Follow-up
      included annual outpatient clinic surveillance and CT angiography examinations,
      which were reviewed for any device-related complications. The radiation effective
      dose was calculated from the CT dose report. RESULTS: Thirty-three CT
      examinations performed 64-110 months (mean 76) after stent-graft implementation
      were reviewed. The mean follow-up number of examinations per patient was 4.7
      (range 2-8). Intra-graft circular mural tissue at the distal part of the stent
      graft was seen in one patient. Stable lack of proximal device apposition was seen
      in all patients. No other radiological complications (e.g., aortic infection,
      dilatation, aneurysm or pseudoaneurysm, device struts breakage, migration,
      collapse, endoleak) were detected. None of the patients developed hypertension.
      The average effective dose was 77.01 mSv (range 34.11-128.84 mSv). CONCLUSION: CT
      angiography did not reveal any complications developing throughout the long-term
      follow-up. These results suggest that long-term CT angiography follow-up may not
      be required.

PMID- 24565645
TI  - Minimal diversity of drug-resistant Mycobacterium tuberculosis strains, South
      Africa.
AB  - Multidrug- (MDR) and extensively drug-resistant tuberculosis (XDR TB) are
      commonly associated with Beijing strains. However, in KwaZulu-Natal, South
      Africa, which has among the highest incidence and mortality for MDR and XDR TB,
      data suggest that non-Beijing strains are driving the epidemic. We conducted a
      retrospective study to characterize the strain prevalence among drug-susceptible,
      MDR, and XDR TB cases and determine associations between strain type and
      survival. Among 297 isolates from 2005-2006, 49 spoligotype patterns were found.
      Predominant strains were Beijing (ST1) among drug-susceptible isolates (27%),
      S/Quebec (ST34) in MDR TB (34%) and LAM4/KZN (ST60) in XDR TB (89%). More than
      90% of patients were HIV co-infected. MDR TB and XDR TB were independently
      associated with mortality, but TB strain type was not. We conclude that, although
      Beijing strain was common among drug-susceptible TB, other strains predominated
      among MDR TB and XDR TB cases. Drug-resistance was a stronger predictor of
      survival than strain type. 

PMID- 24565647
TI  - Applications of piezoelectric surgery in endodontic surgery: a literature review.
AB  - INTRODUCTION: Piezosurgery (piezoelectric bone surgery) devices were developed to
      cut bone atraumatically using ultrasonic vibrations and to provide an alternative
      to the mechanical and electrical instruments used in conventional oral surgery.
      Indications for piezosurgery are increasing in oral and maxillofacial surgery, as
      in other disciplines, such as endodontic surgery. Key features of piezosurgery
      instruments include their ability to selectively cut bone without damaging
      adjacent soft tissue, to provide a clear operative field, and to cut without
      generating heat. Although piezosurgery instruments can be used at most stages of
      endodontic surgery (osteotomy, root-end resection, and root-end preparation), no
      published data are available on the effect of piezosurgery on the outcomes of
      endodontic surgery. To our knowledge, no study has evaluated the effect of
      piezosurgery on root-end resection, and only 1 has investigated root-end
      morphology after retrograde cavity preparation using piezosurgery. METHODS: We
      conducted a search of the PubMed and Cochrane databases using appropriate terms
      and keywords related to the use and applications of piezoelectric surgery in
      endodontic surgery. A hand search also was conducted of issues published in the
      preceding 2 years of several journals. Two independent reviewers obtained and
      analyzed the full texts of the selected articles. RESULTS: A total of 121
      articles published between January 2000 and December 2013 were identified. This
      review summarizes the operating principles of piezoelectric devices and outlines
      the applications of piezosurgery in endodontic surgery using clinical examples.
      CONCLUSIONS: Piezosurgery is a promising technical modality with applications in
      several aspects of endodontic surgery, but further studies are necessary to
      determine the influence of piezosurgery on root-end resection and root-end
      preparation.

PMID- 24565648
TI  - Revascularization outcomes: a prospective analysis of 16 consecutive cases.
AB  - INTRODUCTION: Recent reviews lament the lack of evidence on the efficacy of
      regenerative procedures to induce further root maturation despite claims of a
      paradigm shift in the way infected, necrotic immature teeth with arrested root
      development can be endodontically treated. The majority of reports are either
      case series or successful case reports where nonstandardized images may make
      interpretation uncertain. METHODS: This prospective clinical study reports on
      preliminary outcomes of regenerative endodontic procedures carried out on 16
      teeth, 3 mandibular premolars and 13 traumatized central incisors, after 18-month
      reviews. Qualitative analysis of resolution of periapical radiolucencies and
      apical closure was undertaken. Quantitative analysis compared preoperative and
      recall radiographs by using a geometrical imaging program that calculated
      percentage changes in root length and dentin wall thickness. RESULTS: Qualitative
      assessment showed 90.3% resolution of the periapical radiolucency. Apical closure
      was assessed as incomplete in 47.2% and complete apical closure in 19.4% of
      cases. Quantitative assessment showed change in root length varying from -2.7% to
      25.3% and change for root dentin thickness of -1.9% to 72.6%. CONCLUSIONS:
      Patterns of continued root maturogenesis were variable at 18-month review.
      Reviews at 36 months showed continued root maturogenesis for 2 cases.
      Quantitative analysis can control for changes in angulation but may introduce
      other measurement errors. However, not all anterior teeth were suitable for
      TurboReg assessment because overlapping of the cementoenamel junctions and/or
      further eruption of teeth often precluded stable landmark positioning.
      Discoloration of the crown was a common consequence, with unaesthetic results in
      10 of the 16 cases.

PMID- 24565649
TI  - Beta-lactamic resistance profiles in Porphyromonas, Prevotella, and Parvimonas
      species isolated from acute endodontic infections.
AB  - INTRODUCTION: Susceptibility to beta-lactamic agents has changed among anaerobic
      isolates from acute endodontic infections. The aim of the present study was to
      determine the prevalence of the cfxA/cfxA2 gene in Prevotella spp., Porphyromonas
      spp., and Parviomonas micra strains and show its phenotypic expression. METHODS:
      Root canal samples from teeth with acute endodontic infections were collected and
      Porphyromonas, Prevotella, and Parvimonas micra strains were isolated and
      microbiologically identified with conventional culture techniques. The
      susceptibility of the isolates was determined by the minimum inhibitory
      concentration of benzylpenicillin, amoxicillin, and amoxicillin + clavulanate
      using the E-test method (AB BIODISK, Solna, Sweden). The presence of the
      cfxA/cfxA2 gene was determined through primer-specific polymerase chain reaction.
      The nitrocefin test was used to determine the expression of the lactamase enzyme.
      RESULTS: Prevotella disiens, Prevotella oralis, Porphyromonas gingivalis, and P.
      micra strains were susceptible to benzylpenicillin, amoxicillin, and amoxicillin
      + clavulanate. The cfxA/cfxA2 gene was detected in 2 of 29 isolates (6.9%).
      Simultaneous detection of the cfxA/cfxA2 gene and lactamase production was
      observed for 1 Prevotella buccalis strain. The gene was in 1 P. micra strain but
      was not expressed. Three strains were positive for lactamase production, but the
      cfxA/cfxA2 gene was not detected through polymerase chain reaction. CONCLUSIONS:
      There is a low prevalence of the cfxA/cfxA2 gene and its expression in
      Porphyromonas spp., Prevotella spp., and P. micra strains isolated from acute
      endodontic infections. Genetic and phenotypic screening must be performed
      simultaneously to best describe additional mechanisms involved in lactamic
      resistance for strict anaerobes.

PMID- 24565650
TI  - Evaluation of microsurgery with SuperEBA as root-end filling material for
      treating post-treatment endodontic disease: a 2-year retrospective study.
AB  - INTRODUCTION: This retrospective study assessed the effects of microsurgical
      treatment of post-treatment endodontic disease using SuperEBA (Bosworth, Skokie,
      IL) as the root-end filling material and evaluated the potential prognostic
      factors in relation to outcome. METHODS: Data were collected from patients
      diagnosed with post-treatment endodontic disease who then underwent endodontic
      microsurgery between April 2007 and October 2010. The effect was evaluated 2
      years after the operation. Surgical procedures were performed by a single
      endodontic specialist. After surgery, operation records were recorded including
      preoperative, intraoperative, and postoperative factors from the clinical and
      radiographic measures. For statistical analysis of the predisposing factors, the
      dependent variable was the dichotomous outcome (ie, success vs failure). RESULTS:
      Eighty-two patients with 101 treated teeth met the inclusion criteria. The recall
      rate was 87.2%. Of these microsurgically treated cases, the overall healing rate
      was 93.1%. At the 0.05 significance level, age, sex, tooth position, size of
      periapical radiolucency, biopsy result of periapical lesion, and presence of a
      sinus tract appeared to have no significant effects on the outcome (P > .05).
      CONCLUSIONS: Microsurgical endodontic treatment using SuperEBA as the root-end
      filling material is a favorable option for post-treatment endodontic disease.

PMID- 24565651
TI  - Evaluation of dental pulp sensibility tests in a clinical setting.
AB  - INTRODUCTION: The goal of this project was to evaluate the performance of dental
      pulp sensibility testing with Endo Ice (1,1,1,2-tetrafluoroethane) and an
      electric pulp tester (EPT) and to determine the effect of several variables on
      the reliability of these tests. METHODS: Data were collected from 656 patients
      seen in the University of Iowa College of Dentistry Endodontic graduate clinic.
      The results of pulpal sensibility tests, along with the tooth number, age, sex,
      number of restored surfaces, presence or absence of clinical or radiographic
      caries, and reported recent use of analgesic medications, were recorded. The
      presence of vital tissue within the pulp chamber was used to verify the
      diagnosis. RESULTS: The Endo Ice results showed accuracy, 0.904; sensitivity,
      0.916; specificity, 0.896; positive predictive value, 0.862; and negative
      predictive value, 0.937. The EPT results showed accuracy, 0.75; sensitivity,
      0.84; specificity, 0.74; positive predictive value, 0.58; and negative predictive
      value, 0.90. Patients aged 21-50 years exhibited a more accurate response to cold
      testing (P = .0043). Vital teeth with caries responded more accurately to cold
      testing (P = .0077). There was no statistically significant difference noted with
      any other variable examined. CONCLUSION: Pulpal sensibility testing with Endo Ice
      and EPT are accurate and reliable methods of determining pulpal vitality.
      Patients aged 21-50 exhibited a more accurate response to cold. Sex, tooth type,
      number of restored surfaces, presence of caries, and recent analgesic use did not
      significantly alter the results of pulpal sensibility testing in this study.

PMID- 24565652
TI  - Influence of apical periodontitis on the accuracy of 3 electronic root canal
      length measurement devices: an in vivo study.
AB  - INTRODUCTION: The aim of this in vivo study was to evaluate the influence of
      apical periodontitis (AP) on the accuracy of Dentaport ZX (J Morita, Kyoto,
      Japan), Raypex 5 (VDW, Munich, Germany), and i-Root (S-Denti, Seoul, Korea)
      electronic root canal length measurement devices (ERCLMDs). METHODS: Thirty-two
      single-rooted teeth scheduled for extraction, consisting of 16 teeth with AP and
      16 teeth with normal periapex (NP), were selected. The access cavity was
      prepared, and the coronal portion of the canal was flared. The electronic working
      length (EWL) was determined by each ERCLMD according to each manufacturer's
      instructions. Each tooth was extracted, and the actual working length (AWL) was
      determined by inserting a size 15 K-file until the tip could be seen at a
      position tangential to the major foramen and then 0.5 mm was subtracted from the
      measurement. The distance from the file tip (EWL) to the point 0.5 mm coronal to
      the major foramen (AWL) was calculated. Data were analyzed using the
      nonparametric Fisher exact test and the chi-square test. Statistical significance
      was set at P < .05. RESULTS: The accuracies of Dentaport ZX, Raypex 5, and i-Root
      within +/- 0.5 mm in the AP group were 93.8%, 81.3%, and 75.0%; they were 93.3%,
      86.7%, and 73.3% in the NP group, respectively. There were no significant
      differences between the accuracy of each device in the 2 groups (P > .05).
      Considering the 2 groups of AP and NP, there were no statistically significant
      differences in the accuracy of the ERCLMDs (P > .05). CONCLUSIONS: The presence
      of AP did not influence the accuracy of ERCLMDs.

PMID- 24565653
TI  - A comparative investigation of cone-beam computed tomography and periapical
      radiography in the diagnosis of a healthy periapex.
AB  - INTRODUCTION: This research aimed to compare the appearance of healthy periapical
      tissues on cone-beam computed tomography (CBCT) with periapical radiography and
      to measure the periodontal ligament (PDL) space on CBCT for teeth with healthy
      and necrotic pulps. METHODS: Patient records from specialist endodontic practices
      were examined for teeth that had a high-resolution (0.08-mm voxel) and small
      field-of-view CBCT scan, a periapical radiograph, and clinical pulp tests (CO2
      and electric pulp testing). The periapical regions of the CBCT scans and
      radiographs were scored individually by 2 calibrated, blinded examiners by using
      a modified CBCT-periapical index (CBCT-PAI) for both and represented as CBCT-PAI
      and PAI, respectively. The Fisher exact and chi(2) statistics tested the
      relationships between CBCT-PAI, PAI, and pulp status. RESULTS: Of 200 teeth
      included in the study, 166 showed clinical signs of pulpal health, and the CBCT
      PAI score was greater than the PAI in 72% (119 of 166), with a vital pulp likely
      to have a radiographic PDL space widening of 0-1 mm (P < .001). Although 2
      healthy teeth showed radiolucencies 2-4 mm on CBCT scan when the periapical
      radiograph showed none, a PDL space of greater than 1-2 mm was indicative of a
      necrotic pulp (P < .001). CONCLUSIONS: Teeth with necrotic pulps were more likely
      to have PDL widening, but the PDL space of a healthy tooth demonstrated
      significant variation when examined by CBCT. The radiographic interpretation of
      health and disease on CBCT must be further investigated before usage in outcome
      or epidemiologic investigations. This research questions the traditional
      radiographic interpretation of the PDL space.

PMID- 24565654
TI  - Age and timing of pulp extirpation as major factors associated with inflammatory
      root resorption in replanted permanent teeth.
AB  - INTRODUCTION: External root resorption (ERR) is a serious complication after
      replantation, and its progressive inflammatory and replacement forms are
      significant causes of tooth loss. This retrospective study aimed to evaluate the
      factors related to the occurrence of inflammatory ERR (IERR) and replacement ERR
      (RERR) shortly after permanent tooth replantation in patients treated at the
      Dental Trauma Clinic at the School of Dentistry, Federal University of Minas
      Gerais, Belo Horizonte, Brazil. METHODS: Case records and radiographs of 165
      patients were evaluated for the presence, type, and extension of ERR and its
      association with age and factors related to the management and acute treatment of
      the avulsed tooth by using the logistic regression model. RESULTS: The patient's
      age at the moment of trauma had a marked effect on the ERR prevalence and
      extension. The patients older than 16 years at the moment of trauma had less
      chance of developing IERR and RERR (77% and 87%, respectively) before the pulp
      extirpation, regardless of the extension of the resorption. The patients older
      than 11 years of age at the moment of trauma showed the lowest indices of IERR (P
      = .02). Each day that elapsed between the replantation and the pulp extirpation
      increased the risk of developing IERR and RERR by 1.2% and 1.1%, respectively,
      and also raised the risk of severe IERR by 0.5% per day. CONCLUSIONS: The risk of
      mature teeth developing severe IERR before the onset of endodontic therapy was
      directly affected by the timing of the pulpectomy and was inversely proportional
      to age. Systemic antibiotic therapy use had no effect on the occurrence and
      severity of IERR in mature teeth. The occurrence of RERR before the onset of
      endodontic treatment stimulates further investigations of the early human host
      response to trauma and subsequent infection.

PMID- 24565655
TI  - Effects of pulpectomy on the amount of root resorption during orthodontic tooth
      movement.
AB  - INTRODUCTION: Previous studies have revealed that orthodontic force affects
      dental pulp via the rupture of blood vessels and vacuolization of pulp tissues.
      We hypothesized that pulp tissues express inflammatory cytokines and regulators
      of odontoclast differentiation after excess orthodontic force. The purpose of
      this study was to investigate the effects of tensile force in human pulp cells
      and to measure inflammatory root resorption during tooth movement in pulpless rat
      teeth. METHODS: After cyclic tensile force application in human pulp cells, gene
      expression and protein concentration of macrophage colony-stimulating factor,
      receptor activator of nuclear factor kappa-B ligand, interleukin-1 beta, and
      tumor necrosis factor alpha were determined by real-time polymerase chain
      reaction and enzyme-linked immunoassay. Moreover, the role of the stretch
      activated channel was evaluated by gadolinium (Gd(3+)) treatment. The upper right
      first molars of 7-week Wistar rats were subjected to pulpectomy and root canal
      filling followed by mesial movement for 6 months. RESULTS: The expression of
      cytokine messenger RNAs and proteins in the experimental group peaked with
      loading at 10-kPa tensile force after 48 hours (P < .01). Gd(3+) reduced the
      expression of these cytokine messenger RNAs and protein concentrations (P < .01).
      The amount of inflammatory root resorption was significantly larger in the
      control teeth than the pulpectomized teeth (P < .05). CONCLUSIONS: This study
      shows that tensile forces in the pulp cells enhance the expression of various
      cytokines via the S-A channel, which may lead to inflammatory root resorption
      during tooth movement. It also suggests that root canal treatment is effective
      for progressive severe inflammatory root resorption during tooth movement.

PMID- 24565656
TI  - M2 macrophages participate in the biological tissue healing reaction to mineral
      trioxide aggregate.
AB  - INTRODUCTION: This study examined the protein and messenger RNA (mRNA) expression
      of molecules associated with M2 (wound healing) macrophages in mineral trioxide
      aggregate (MTA)-implanted rat subcutaneous tissue to elucidate the involvement of
      M2 macrophages in the connective tissue response to MTA. METHODS: Silicone tubes
      containing freshly mixed MTA or a calcium hydroxide cement (Life; Kerr, Romulus,
      MI) were subcutaneously implanted into the backs of Wistar rats. Solid silicone
      rods implanted in different animals served as controls. The specimens were then
      double immunostained for ED1 (CD68, a general macrophage marker) and ED2 (CD163,
      an M2 macrophage marker). Immunostaining for CD34 (a marker for vascularization
      and wound healing) was also performed. Expression levels of CD34, CD163, and
      mannose receptor c type 1 (an M2 macrophage marker) mRNAs were determined with
      real-time polymerase chain reaction. RESULTS: MTA-implanted subcutaneous tissues
      showed significant increases in the density of ED1+ED2+ macrophages beneath the
      implantation site and expression levels of CD163 and MMR mRNAs compared with Life
      implanted and control tissues. MTA-implanted subcutaneous tissues also showed a
      significant increase of CD34-immunostained areas and up-regulation of CD34 mRNAs
      compared with Life-implanted and control tissues. CONCLUSIONS: MTA implantation
      induced the accumulation of M2 macrophage marker (ED2)-expressing macrophages and
      enhanced the expression of M2 macrophage marker genes. MTA implantation also
      enhanced the expression of CD34, suggesting acceleration of the healing/tissue
      repair process. Taken together, biological connective tissue response to MTA may
      involve wound healing/tissue repair processes involving M2 macrophages.

PMID- 24565657
TI  - Methylation pattern of the CD14 and TLR2 genes in human dental pulp.
AB  - INTRODUCTION: Pattern recognition receptors, such as toll-like receptor 2 (TLR-2)
      and TLR-4, participate in the activation of immune cells by microorganisms in
      dental pulp. However, the expression levels of pattern recognition receptors can
      be modulated by epigenetic factors, especially DNA methylation. In this study,
      the methylation status of the TLR-2 and CD14 (TLR4 co-receptor) genes in healthy
      and inflamed human dental pulp was examined. METHODS: The Methyl-Profiler DNA
      Methylation qPCR Assay was used to verify the DNA methylation patterns. RESULTS:
      No differences in the methylation patterns were observed between the 2 groups.
      Most DNA was unmethylated in both groups. CONCLUSIONS: The hypomethylation of
      TLR2 and CD14 genes is a usual feature in human dental pulp.

PMID- 24565658
TI  - Gene expression and cytokine release during odontogenic differentiation of human
      dental pulp stem cells induced by 2 endodontic biomaterials.
AB  - INTRODUCTION: Mineral trioxide aggregate (MTA) and calcium-enriched mixture (CEM)
      have shown osteogenic/cementogenic/dentinogenic activities; however, their
      mechanism of action is not fully understood. We aimed to evaluate the effect of
      these biomaterials on odontogenic differentiation of human dental pulp stem cells
      (DPSCs). METHODS: Flow cytometry with stem cell markers for the confirmation of
      stemness and homogeneity was first performed. Then isolated DPSCs were seeded on
      prepared discs of MTA, CEM, differentiation medium (DM), and growth medium (GM)
      and incubated up to 14 days. Concentrations of transforming growth factor-beta1,
      bone morphogenetic protein (BMP)2, BMP4, and fibroblast growth factor 4 were
      measured at each interval using an enzyme-linked immunosorbent assay reader. Gene
      expression of dentin sialophosphoprotein, dentin matrix protein 1, and the
      cytokines were evaluated by reverse-transcription polymerase chain reaction. To
      evaluate the cell morphology, scanning electron micrographs were taken;
      mineralization potential was evaluated using alizarin red S staining. RESULTS:
      Scanning electron micrographs showed that DPSCs spread/adhered/proliferated
      similarly on MTA and CEM. On day 14, alizarin red S staining confirmed that
      mineralization occurred in all groups except GM. Expressions of dentin matrix
      protein 1 and dentin sialophosphoprotein genes were similar in the CEM, MTA, and
      DM groups; they were significantly higher compared with the GM group (P < .05). A
      greater amount of transforming growth factor-beta1 gene was expressed in MTA
      compared with the other groups (P < .05). However, the expression of fibroblast
      growth factor 4 and BMP2 genes was significantly greater in the CEM group (P <
      .05). In all the tested groups, the expression of BMP4 was less than GM (P <
      .01); however, CEM and DM were similar but more than MTA (P < .05).
      Concentrations of protein product detected using an enzyme-linked immunosorbent
      assay reader confirmed these gene expressions. CONCLUSIONS: MTA and CEM can
      induce osteo-/odontogenic-like phenotype differentiation of human DPSCs; however,
      they stimulate different gene expressions and growth factor release.

PMID- 24565659
TI  - The effect of SIRT6 on the odontoblastic potential of human dental pulp cells.
AB  - INTRODUCTION: The aim of this study was to investigate whether SIRT6 is expressed
      in human dental pulp as well as the effect of SIRT6 on proliferation and
      odontoblastic differentiation of human dental pulp cells (HDPCs). METHODS:
      Immunohistochemical and immunocytochemical assays were used to detect the
      expression of SIRT6 in human dental pulp tissue and HDPCs. To determine the
      effect of SIRT6 on odontoblast differentiation, HDPCs with loss (HDPCs SIRT6
      knockdown) and gain (HDPCs SIRT6 overexpression) of SIRT6 function were
      developed, and their proliferation ability was examined. Odontogenic
      differentiation of HDPCs was determined by alkaline phosphatase (ALP) activity,
      ALP-positive cell staining, alizarin red staining, and von Kossa staining.
      Mineralization-related genes, including ALP, dentin sialophosphoprotein (DSPP),
      and dentin matrix acidic phosphoprotein 1, were determined by real-time
      quantitative polymerase chain reaction. Western blot analysis was performed to
      detect the expression of DSPP protein. RESULTS: SIRT6 was found in the dental
      pulp tissue and HDPCs. SIRT6 knockdown decreased ALP activity in HDPCs; calcium
      nodule formation ability; and the expression of mineralization-related genes such
      as ALP, DSPP, and DMP1, whereas these were increased with the overexpression of
      SIRT6. CONCLUSIONS: SIRT6 is expressed in human dental pulp and participates in
      the odontoblast differentiation of HDPCs.

PMID- 24565660
TI  - Regenerative capacity of human dental pulp and apical papilla cells after
      treatment with a 3-antibiotic mixture.
AB  - INTRODUCTION: A 3-antibiotic combination (3Mix) has been widely used in
      regenerative endodontics. Recent studies recommend that a safe concentration of
      3Mix is in the range of 0.39 MUg/mL and 1 mg/mL because higher concentrations may
      limit tissue regeneration. The aim of this study was to determine the
      regenerative capacity of isolated human dental pulp cells (DPCs) and apical
      papilla cells (APCs) after a 7-day treatment with selected doses of 3Mix.
      METHODS: Primary human DPCs/APCs from the third passage were divided into control
      and experimental groups. In the control group, cells were cultured in regular
      complete media. In the experimental group, cells were cultured in complete media
      containing 0.39 MUg/mL or 1 mg/mL of 3Mix for 7 days. After the treatment period,
      the media were changed, and the cells were further tested for proliferation and
      differentiation potential. For cell proliferation, a colorimetric qualification
      of 3-[4, 5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide was used on
      days 1, 3, 5, and 7. For differentiation potential, a dentinogenic
      differentiation medium was added into treated cells and cultured for 7, 14, and
      21 days. Results were analyzed using quantitative alizarin red S staining and
      real-time reverse-transcription polymerase chain reaction. RESULTS: After 7 days
      of treatment, 100% cell death was discovered in the 1-mg/mL 3Mix group. The
      proliferative capacity of 0.39 MUg/mL 3Mix-treated DPCs and APCs was
      significantly lower than that of untreated cells at all time points (P < .05).
      Mineralized nodule formation was found both in the 3Mix-treated and control
      groups, but it was significantly less in the 3Mix-treated groups at 7, 14, and 21
      days (P < .01). Quantitative reverse-transcription polymerase chain reaction
      showed no statistically significant difference (95% confidence interval) in bone
      sialoprotein, alkaline phosphatase, and dentin matrix protein 1 gene expression
      in either 3Mix-treated DPCs or APCs compared with control groups. CONCLUSIONS:
      One milligram per milliliter of 3Mix had strong toxicity to DPCs/APCs when
      applied for 7 days, whereas 0.39 MUg/mL 3Mix showed no toxicity but still
      affected cell proliferation and mineralization potential. However, no differences
      in dentinogenic gene expressions were observed between the 3Mix-treated and
      untreated groups.

PMID- 24565661
TI  - Biodentine and mineral trioxide aggregate induce similar cellular responses in a
      fibroblast cell line.
AB  - INTRODUCTION: The aim of this study was to assess the cell viability and
      messenger RNA expression of interleukin (IL)-1alpha and IL-6 in 3T3 fibroblast
      cells when in direct contact with Biodentine (Septodont, Saint Maur de Fosses,
      France) and mineral trioxide aggregate (MTA). METHODS: Biodentine and MTA were
      coated onto coverslips and allowed to set. An uncoated coverslip and one coated
      with GC Fuji IX (GC Corporation, Tokyo, Japan) were used as controls. Coverslips
      were cultured with 3T3 fibroblast cells. Cell viability was assessed
      quantitatively using AlamarBlue dye (Serotec, Oxford, UK) after 3, 6, 24, and 72
      hours. Morphologic cell changes of 3T3 cells in contact with BD and MTA were
      observed by scanning electron microscopy, and cytokine expression was assessed at
      the messenger RNA level by semiquantitative reverse-transcription polymerase
      chain reaction after 3 and 24 hours of direct contact with the materials.
      RESULTS: Cells in contact with Biodentine and MTA showed similar viability to
      untreated control cells at all time points, with the exception of 6 hours when
      viability was decreased with both treatments. Examination by scanning electron
      microscopy revealed cells adhering to most of the Biodentine surface after 24
      hours. However, for MTA samples, significantly fewer cells were observed. The
      messenger RNA expression of IL-1alpha and IL-6 by cells in contact with
      Biodentine was similar to cells in contact with MTA. CONCLUSIONS: Biodentine and
      MTA showed similar cytotoxicity and induced a similar pattern of cytokine
      expression.

PMID- 24565662
TI  - In vitro particle image velocity measurements in a model root canal: flow around
      a polymer rotary finishing file.
AB  - INTRODUCTION: Root canal irrigation is vital to thorough debridement and
      disinfection, but the mechanisms that contribute to its effectiveness are complex
      and uncertain. Traditionally, studies in this area have relied on before-and
      after static comparisons to assess effectiveness, but new in situ tools are being
      developed to provide real-time assessments of irrigation. The aim in this work
      was to measure a cross section of the velocity field in the fluid flow around a
      polymer rotary finishing file in a model root canal. METHODS: Fluorescent
      microparticles were seeded into an optically accessible acrylic root canal model.
      A polymer rotary finishing file was activated in a static position. After laser
      excitation, fluorescence from the microparticles was imaged onto a frame-transfer
      camera. Two consecutive images were cross-correlated to provide a measurement of
      a projected, 2-dimensional velocity field. RESULTS: The method reveals that fluid
      velocities can be much higher than the velocity of the file because of the shape
      of the file. Furthermore, these high velocities are in the axial direction of the
      canal rather than only in the direct of motion of the file. CONCLUSIONS: Particle
      image velocimetry indicates that fluid velocities induced by the rotating file
      can be much larger than the speed of the file. Particle image velocimetry can
      provide qualitative insight and quantitative measurements that may be useful for
      validating computational fluid dynamic models and connecting clinical
      observations to physical explanations in dental research.

PMID- 24565663
TI  - Comparison of alternative image reformatting techniques in micro-computed
      tomography and tooth clearing for detailed canal morphology.
AB  - INTRODUCTION: Micro-computed tomography (MCT) shows detailed root canal
      morphology that is not seen with traditional tooth clearing. However, alternative
      image reformatting techniques in MCT involving 2-dimensional (2D) minimum
      intensity projection (MinIP) and 3-dimensional (3D) volume-rendering
      reconstruction have not been directly compared with clearing. The aim was to
      compare alternative image reformatting techniques in MCT with tooth clearing on
      the mesiobuccal (MB) root of maxillary first molars. METHODS: Eighteen maxillary
      first molar MB roots were scanned, and 2D MinIP and 3D volume-rendered images
      were reconstructed. Subsequently, the same MB roots were processed by traditional
      tooth clearing. Images from 2D, 3D, 2D + 3D, and clearing techniques were
      assessed by 4 endodontists to classify canal configuration and to identify fine
      anatomic structures such as accessory canals, intercanal communications, and
      loops. RESULTS: All image reformatting techniques in MCT showed detailed
      configurations and numerous fine structures, such that none were classified as
      simple type I or II canals; several were classified as types III and IV according
      to Weine classification or types IV, V, and VI according to Vertucci; and most
      were nonclassifiable because of their complexity. The clearing images showed less
      detail, few fine structures, and numerous type I canals. Classification of canal
      configuration was in 100% intraobserver agreement for all 18 roots visualized by
      any of the image reformatting techniques in MCT but for only 4 roots (22.2%)
      classified according to Weine and 6 (33.3%) classified according to Vertucci,
      when using the clearing technique. CONCLUSIONS: The combination of 2D MinIP and
      3D volume-rendered images showed the most detailed canal morphology and fine
      anatomic structures.

PMID- 24565664
TI  - Particle size changes in unsealed mineral trioxide aggregate powder.
AB  - INTRODUCTION: Mineral trioxide aggregate (MTA) is commonly supplied in 1-g
      packages of powder that are used by some clinicians across several treatments
      against the manufacturer's instructions. ProRoot MTA cannot be resealed after
      opening, whereas MTA Angelus has a resealable lid. This study assessed changes in
      particle size distribution once the packaging had been opened. METHODS: Fresh
      ProRoot MTA and MTA Angelus powder were analyzed by using laser diffraction and
      scanning electron microscopy and compared with powder from packages that had been
      opened once and kept in storage for 2 years. The ProRoot packet was folded over,
      whereas the MTA Angelus jar had the lid twisted back to its original position.
      RESULTS: After 2 years, ProRoot MTA powder showed a 6-fold increase in particle
      size (lower 10% from 1.13 to 4.37 MUm, median particle size from 1.99 to 12.87
      MUm, and upper 10% from 4.30 to 34.67 MUm), with an accompanying 50-fold change
      in particle surface area. MTA Angelus showed only a 2-fold increase in particle
      size (4.15 to 8.32 MUm, 12.72 to 23.79 MUm, and 42.66 to 47.91 MUm, respectively)
      and a 2-fold change in particle size surface area. CONCLUSIONS: MTA reacts with
      atmospheric moisture, causing an increase in particle size that may adversely
      affect the properties and shelf life of the material. Smaller particles have a
      greater predisposition to absorb moisture. Single-use systems are advised.

PMID- 24565665
TI  - Antimicrobial activity and cytotoxicity of 3 photosensitizers activated with blue
      light.
AB  - INTRODUCTION: Pulp repair is less likely to occur when dentin or pulpal tissue
      remains infected after caries excavation. Yet there are currently few options to
      kill residual bacteria without damaging resident cells. The current study has
      evaluated the effect of 3 blue light-activated chemicals on the viability of
      lactobacilli, odontoblast-like cells (MDPC-23), undifferentiated pulp cells
      (OD21), and human embryonic stem cells (hESC H1). METHODS: Bacteria were
      incubated for 15 minutes with curcumin, eosin Y, or rose bengal and then
      irradiated with blue light (240 seconds). Bacteria were labeled with LIVE/DEAD
      BacLight Bacterial Viability kit, and viability was assessed by fluorescence
      activated cell sorting. Cytotoxicity assays were performed on MDPC-23 cells,
      OD21, and hESC H1 cells grown in 24-well plates and exposed to the same
      photosensitizer-light combination. After 24 hours, cellular response was measured
      by using the methyl-thiazol-diphenyl-tetrazolium assay. Results were
      statistically analyzed by using one-way analysis of variance and Tukey multiple
      comparison intervals (alpha = 0.05). RESULTS: Bacterial viability was
      significantly reduced after exposure to different combinations of light and
      photosensitizers; mitochondrial activity of cultured cells remained unaffected
      when exposed to the same conditions, suggesting a good therapeutic index in
      vitro. CONCLUSIONS: Blue light-mediated disinfection is promising for the
      development of new treatment strategies designed to promote pulp repair after
      carious exposure.

PMID- 24565666
TI  - Acid and microhardness of mineral trioxide aggregate and mineral trioxide
      aggregate-like materials.
AB  - INTRODUCTION: The aim of this study was to compare the surface microhardness of
      BioAggregate, ProRoot MTA, and CEM Cement when exposed to an acidic environment
      or phosphate-buffered saline (PBS) as a synthetic tissue fluid. METHODS: Ninety
      cylindrical molds made of polymethyl methacrylate with an internal diameter of 6
      mm and height of 4 mm (according to ASTM E384 standard for microhardness tests)
      were fabricated and filled with BioAggregate (n = 30), tooth-colored ProRoot MTA
      (n = 30), or CEM Cement (n = 30). Each group was then divided into 3 subgroups of
      10 specimens consisting of those exposed to distilled water, exposed to PBS (pH =
      7.4), or exposed to butyric acid (pH = 5.4). After 1 week the Vickers surface
      microhardness test was performed. Statistical analysis included 2-way analysis of
      variance, followed by post hoc Dunnett T3 in cases with lack of homoscedasticity
      and Tukey honestly significant difference in cases with homoscedasticity.
      RESULTS: The indentations obtained from the CEM Cement specimens exposed to an
      acidic pH were not readable because of incomplete setting. There was a
      significant difference between the microhardness of the materials regardless of
      the environmental conditions (P < .001). In all the environmental conditions, MTA
      had significantly higher and CEM Cement had significantly lower microhardness
      values (P < .001). All experimental cements had significantly higher
      microhardness values when exposed to PBS (P < .001) and had significantly lower
      microhardness values when exposed to butyric acid (P < .001). CONCLUSIONS: The
      surface microhardness of BioAggregate, ProRoot MTA, and CEM Cement was reduced
      significantly by exposure to butyric acid and increased significantly by exposure
      to PBS. In all environmental conditions, MTA had significantly higher
      microhardness values.

PMID- 24565667
TI  - Color stability of white mineral trioxide aggregate in contact with hypochlorite
      solution.
AB  - INTRODUCTION: One of the uses of white mineral trioxide aggregate (MTA) is as an
      apical barrier in immature teeth. Although this treatment has been reported to
      have high success rates, a number of cases of discoloration have been noted. The
      aim of this research was to investigate the color stability of white MTA in
      contact with various solutions used in endodontics. METHODS: The change in color
      of white MTA after immersion in water, sodium hypochlorite, or hydrogen peroxide
      was assessed by viewing the color change on digital photographs and also by using
      a spectrophotometer. White MTA, white Portland cement, and bismuth oxide were
      assessed. The changes in the material after immersion in the different solutions
      were assessed by x-ray diffraction analysis and Fourier transform infrared
      spectroscopy. RESULTS: Immersion of white MTA and bismuth oxide in sodium
      hypochlorite resulted in the formation of a dark brown discoloration. This change
      was not observed in Portland cement. X-ray diffraction analysis and Fourier
      transform infrared analysis displayed the reduction of sodium hypochlorite in
      contact with bismuth oxide and MTA to sodium chloride. CONCLUSIONS: Contact of
      white MTA and other bismuth-containing materials with sodium hypochlorite
      solution should be avoided.

PMID- 24565668
TI  - Effect of various mixing and placement techniques on the flexural strength and
      porosity of mineral trioxide aggregate.
AB  - INTRODUCTION: The aim of this study was to evaluate the effect of mechanical and
      manual mixing as well as the effect of ultrasonic agitation during placement on
      the flexural strength and porosity of mineral trioxide aggregate (MTA). METHODS:
      White ProRoot MTA and white MTA Angelus were used. One gram of each powder was
      mixed with a 0.34-g aliquot of distilled water. Specimens were mixed either by
      mechanical mixing of capsules for 30 seconds at 4500 rpm or by a saturation
      technique and application of a condensation pressure of 3.22 MPa for 1 minute.
      The mixed slurries of all materials were loaded into 2 * 2 * 25 mm molds for
      testing flexural strength and 3 * 4 mm molds for evaluation of porosity. Half of
      the specimens were placed in the stainless steel molds by using indirect
      ultrasonic activation. All specimens were incubated for 4 days. Micro-computed
      tomography was used to determine the porosity of each specimen, and a 3-point
      bending test was used to evaluate flexural strength. Tukey honestly significant
      difference and independent t tests were carried out to compare the means at a
      significance level of P < .05. RESULTS: Irrespective of mixing and placement
      techniques applied, the flexural strength values of ProRoot MTA were
      significantly greater than those of MTA Angelus (P < .05). A medium negative
      correlation was found between flexural strength values and total porosity
      percentage. CONCLUSIONS: Although mechanical mixing of encapsulated cements was
      quicker and provided more consistent mixes, this technique along with ultrasonic
      agitation was not associated with a significant advantage in terms of flexural
      strength and total porosity over manual mixing.

PMID- 24565669
TI  - Comparison of the efficacy of Smear Clear with and without a canal brush in smear
      layer and debris removal from instrumented root canal using WaveOne versus
      ProTaper: a scanning electron microscopic study.
AB  - INTRODUCTION: The aim of this study was to compare by scanning electron
      microscopy the presence of smear layer and debris on root canal walls after
      preparation with the single-file system WaveOne (Dentsply Maillefer, Ballaigues,
      Switzerland) versus the rotary ProTaper system (Dentsply Maillefer, Ballaigues,
      Switzerland) under 2 final irrigant regimens. METHODS: Forty freshly extracted
      single-rooted human teeth were randomly divided into 4 groups (n = 10). The
      ProTaper and ProTaper and rotary CanalBrush (Coltene Whaledent GmbH+ Co KG,
      Langenau, Germany) groups were instrumented with the ProTaper system. Groups
      WaveOne and WaveOne and rotary CanalBrush were instrumented with the WaveOne
      system. The irrigant in all groups was 2 mL 5.25% sodium hypochlorite (NaOCl)
      solution, whereas the final irrigation after preparation in the ProTaper and
      WaveOne groups was 1 mL Smear Clear solution (Sybron Endo, Orange, CA) and then
      5.25% NaOCl applied with a plastic syringe, and in the ProTaper and rotary
      CanalBrush and WaveOne and rotary CanalBrush groups, it was 1 mL Smear Clear
      solution and then 5.25% NaOCl (rotary CanalBrush agitation). Roots were processed
      for scanning electron microscopic examination for debris and smear layer scoring.
      Data were statistically analyzed. RESULTS: All groups showed more efficient smear
      layer and debris removal coronally than in the middle and apical regions, whereas
      the mean total debris score and the mean smear layer score in all groups were
      less in the WaveOne and rotary CanalBrush groups than the ProTaper and rotary
      CanalBrush and the WaveOne and ProTaper groups. CONCLUSIONS: Using the rotary
      CanalBrush in canals prepared with WaveOne produced the cleanest canal walls, and
      the WaveOne system gave superior results compared with the ProTaper system.

PMID- 24565670
TI  - Effect of different final irrigation methods on the removal of calcium hydroxide
      from an artificial standardized groove in the apical third of root canals.
AB  - INTRODUCTION: The aim of this study was to compare the efficacy of conventional
      syringe, ultrasonic, EndoVac (Discus Dental, Culver City, CA), and Self-Adjusting
      File (SAF) (Re-Dent-Nova, Ra'nana, Israel) irrigation systems in removing calcium
      hydroxide (Ca[OH]2) from simulated root canal irregularities. METHODS: The root
      canals of 88 extracted single-rooted teeth were prepared using ProTaper rotary
      instruments (Dentsply Maillefer, Ballagiues, Switzerland) up to size F4. The
      roots were split longitudinally, and a standardized groove was prepared in the
      apical part of 1 segment. The root halves were reassembled, and Ca(OH)2
      medicament was placed into the root canals using a Lentulo spiral. The roots were
      randomly divided into 4 experimental groups and 2 control groups according to the
      different irrigation systems used: conventional syringe irrigation, continuous
      passive ultrasonic irrigation (PUI), EndoVac irrigation, and SAF irrigation. Each
      group was then divided into 2 subgroups (n = 10) according to the irrigation
      protocol: subgroup 1: 10 mL 2.5% NaOCl and subgroup 2: 10 mL 17% EDTA + 10 mL
      2.5% NaOCl. The amount of remaining medicament was evaluated under a
      stereomicroscope at 30* magnification using a 4-grade scoring system. The
      influences of the different Ca(OH)2 medicament removal methods and irrigation
      protocols were statistically evaluated using 2-way analysis of variance and Tukey
      post hoc tests. RESULTS: In the NaOCl-irrigated groups, PUI removed significantly
      more Ca(OH)2 medicament than the other techniques (P < .05). There was no
      significant difference among the other groups (P > .05). In the EDTA/NaOCl
      irrigated groups, the SAF and PUI removed significantly more Ca(OH)2 than the
      other techniques (P < .05). CONCLUSIONS: The use of the SAF system with the
      combination of EDTA and NaOCl enhanced Ca(OH)2 removal when compared with the use
      of only NaOCl irrigation with the SAF. Continuous PUI and SAF were more effective
      than EndoVac, and conventional syringe irrigation in the removal of the Ca(OH)2
      medicament from an artificial standardized groove in the apical part of the root
      canal.

PMID- 24565671
TI  - Orthokeratinized odontogenic cysts presenting as a periapical lesion: report of a
      case and literature review.
AB  - INTRODUCTION: Inflammatory cysts, granulomas, abscesses, and fibrous scars
      represent most periapical radiolucencies. However, other less common lesions,
      such as orthokeratinized odontogenic cysts (OOCs), can be found at this region,
      and they deserve to be discussed because the prognosis for an OOC is different
      from that expected for the ordinary inflammatory periapical diseases. METHODS: An
      interesting case of OOC associated with a nonvital tooth in a 40-year-old woman
      is described. After a previous clinical diagnosis of a radicular cyst, the tooth
      was extracted, and the lesion was enucleated and submitted to microscopy
      examination. RESULTS: Because of the detection of an orthokeratinized epithelium
      lining, a diagnosis of OOC was concluded. After 2 years of periodic follow-up, no
      signs of recurrence were detected. CONCLUSIONS: The presence of keratin in
      radicular lesions must be carefully evaluated to eliminate the diagnosis of
      lesions with more aggressive behavior, such as an OOC or even a keratocystic
      odontogenic tumor. Hence, histopathologic examination is mandatory to confirm the
      type of lesion and to differentiate other pathologic conditions, therefore
      establishing patients' prognoses precisely.

PMID- 24565672
TI  - Decontamination of chemical agents from drinking water infrastructure: a
      literature review and summary.
AB  - This report summarizes the current state of knowledge on the persistence of
      chemical contamination on drinking water infrastructure (such as pipes) along
      with information on decontamination should persistence occur. Decontamination
      options for drinking water infrastructure have been explored for some chemical
      contaminants, but important data gaps remain. In general, data on chemical
      persistence on drinking water infrastructure is available for inorganics such as
      arsenic and mercury, as well as select organics such as petroleum products,
      pesticides and rodenticides. Data specific to chemical warfare agents and
      pharmaceuticals was not found and data on toxins is scant. Future research
      suggestions focus on expanding the available chemical persistence data to other
      common drinking water infrastructure materials. Decontaminating agents that
      successfully removed persistent contamination from one infrastructure material
      should be used in further studies. Methods for sampling or extracting chemical
      agents from water infrastructure surfaces are needed. 

PMID- 24565673
TI  - Berry anthocyanins suppress the expression and secretion of proinflammatory
      mediators in macrophages by inhibiting nuclear translocation of NF-kappaB
      independent of NRF2-mediated mechanism.
AB  - The objectives of this study were to compare the anti-inflammatory effects of
      anthocyanins from blueberry (BBA), blackberry (BKA), and blackcurrant (BCA) and
      to determine the relationship between their antioxidant capacity and anti
      inflammatory effect in macrophages. Major anthocyanins in BBA, BKA and BCA were
      malvidin-3-glucoside (16%), cyanidin-3-glucoside (98%) and delphinidin-3
      rutinoside (44%), respectively. BKA showed higher total antioxidant capacity than
      BBA and BCA. RAW 264.7 macrophages were incubated with 0-20 MUg/ml of BBA, BKA
      and BCA, and subsequently activated by lipopolysaccharide (LPS) to measure
      proinflammatory cytokine production. Interleukin 1beta (IL-1beta) messenger RNA
      (mRNA) levels were significantly decreased by all berry anthocyanins at 10 MUg/ml
      or higher. Tumor necrosis factor alpha (TNFalpha) mRNA levels and secretion were
      also significantly decreased in LPS-treated macrophages. The levels of the
      repression were comparable for all berry anthocyanins. LPS-induced nuclear factor
      kappaB (NF-kappaB) p65 translocation to the nucleus was markedly attenuated by
      all of the berry anthocyanins. In bone marrow-derived macrophages (BMMs) from
      nuclear factor E2-related factor 2 wild-type (Nrf2(+/+)) mice, BBA, BKA and BCA
      significantly decreased cellular reactive oxygen species (ROS) levels with a
      concomitant decrease in IL-1beta mRNA levels upon LPS stimulation. However, in
      the BMM from Nrf2(-/-) mice, the anthocyanin fractions were able to significantly
      decrease IL-1beta mRNA despite the fact that ROS levels were not significantly
      affected. In conclusion, BBA, BKA and BCA exert their anti-inflammatory effects
      in macrophages, at least in part, by inhibiting nuclear translocation of NF
      kappaB independent of the NRF2-mediated pathways. 

PMID- 24565674
TI  - High-fructose diet leads to visceral adiposity and hypothalamic leptin resistance
      in male rats--do glucocorticoids play a role?
AB  - Fructose overconsumption has been involved in the genesis and progression of the
      metabolic syndrome. Hypothalamus and adipose tissue, major organs for control of
      food intake and energy metabolism, play crucial roles in metabolic homeostasis.
      We hypothesized that glucocorticoid signaling mediates the effects of a fructose
      enriched diet on visceral adiposity by acting on neuropeptide Y (NPY) in the
      hypothalamus and altering adipogenic transcription factors in the visceral
      adipose tissue. We analyzed the effects of 9-week consumption of 60% fructose
      solution on dyslipidemia, insulin and leptin sensitivity, and adipose tissue
      histology in male Wistar rats. Glucocorticoid signaling was assessed in both
      hypothalamus and visceral adipose tissue, while the levels of peroxisome
      proliferator-activated receptor gamma (PPARgamma), sterol regulatory element
      binding protein-1 (SREBP-1) and lipin-1, together with the levels of their target
      genes expression, were analyzed in the visceral adipose tissue. The results
      showed that long-term consumption of highly concentrated liquid fructose led to
      the development of visceral adiposity, elevated triglycerides and hypothalamic
      leptin resistance accompanied by stimulated glucocorticoid signaling and NPY mRNA
      elevation. Results from adipose tissue implied that fructose consumption shifted
      the balance between glucocorticoid receptor and adipogenic transcriptional
      factors (PPARgamma, SREBP-1 and lipin-1) in favor of adipogenesis judged by
      distinctly separated populations of small adipocytes observed in this tissue. In
      summary, we propose that high-fructose-diet-induced alterations of glucocorticoid
      signaling in both hypothalamus and adipose tissue result in enhanced
      adipogenesis, possibly serving as an adaptation to energy excess in order to
      limit deposition of fat in nonadipose tissues. 

PMID- 24565675
TI  - Dietary supplementation of aspartate enhances intestinal integrity and energy
      status in weanling piglets after lipopolysaccharide challenge.
AB  - The intestine has a high requirement for ATP to support its integrity, function
      and health, and thus, energy deficits in the intestinal mucosa may play a
      critical role in intestinal injury. Aspartate (Asp) is one of the major sources
      of ATP in mammalian enterocytes via mitochondrial oxidation. We hypothesized that
      dietary supplementation of Asp could attenuate lipopolysaccharide (LPS)-induced
      intestinal damage via modulation of intestinal energy status. Twenty-four
      weanling piglets were allotted to one of four treatments: (1) nonchallenged
      control, (2) LPS-challenged control, (3) LPS+0.5% Asp treatment, and (4) LPS+1.0%
      Asp treatment. On day 19, pigs were injected with saline or LPS. At 24 h
      postinjection, pigs were killed and intestinal samples were obtained. Asp
      attenuated LPS-induced intestinal damage indicated by greater villus height and
      villus height/crypt depth ratio as well as higher RNA/DNA and protein/DNA ratios.
      Asp improved intestinal function indicated by increased intestinal mucosal
      disaccharidase activities. Asp also improved intestinal energy status indicated
      by increased ATP, ADP and total adenine nucleotide contents, adenylate energy
      charge and decreased AMP/ATP ratio. In addition, Asp increased the activities of
      tricarboxylic acid cycle key enzymes including citrate synthase, isocitrate
      dehydrogenase and alpha-oxoglutarate dehydrogenase complex. Moreover, Asp down
      regulated mRNA expression of intestinal AMP-activated protein kinase alpha1
      (AMPKalpha1), AMPKalpha2, silent information regulator 1 (SIRT1) and peroxisome
      proliferator-activated receptor gamma coactivator-1alpha (PGC1alpha) and
      decreased intestinal AMPKalpha phosphorylation. These results indicate that Asp
      may alleviate LPS-induced intestinal damage and improve intestinal energy status.

PMID- 24565676
TI  - Tamoxifen compared to best supportive care in advanced hepatocelluar carcinoma: A
      retrospective matched-cohort study.
AB  - BACKGROUND: Hepatocelluar carcinoma (HCC) is a common cancer worldwide as well as
      in Egypt with hepatitis B and C, alcohol and aflatoxins being the commonest risk
      factors. Tamoxifen was initially reported to confer a marginal survival benefit
      in advanced HCC. However, later reports declined any benefit. OBJECTIVE: To study
      the impact of tamoxifen on overall survival (OS) compared to best supportive care
      (BSC) in Egyptian patients with advanced HCC. METHODS: This retrospective matched
      cohort study was conducted at Tanta Cancer Center (TCC), Egypt where 116 advanced
      HCC cases treated with tamoxifen were compared to TNM stage and Child-Pugh class
      matched 116 HCC cases who received BSC. RESULTS: The median OS in the tamoxifen
      group was 9.3 months (95% confidence interval [CI], 6.7-11.9 months) compared to
      8.7 months (95%CI, 6.8-10.6) in the BSC group (p=0.758). With univariate
      analyses, it was shown that absence of fatigue, Child-Pugh class A, single
      tumors, less advanced tumors (T2), and absence of metastases (M0), had
      significantly better OS than their counterparts. Multivariate analysis showed
      that absence of fatigue, Child-Pugh class A and T2 tumors were independent
      prognostic factors affecting OS. Tamoxifen produced partial response and clinical
      stabilization in one% and 16% of cases, respectively. The median PFS with
      tamoxifen was 7.2 months (95%CI, 5.2-9.5). CONCLUSIONS: Tamoxifen did not show
      any OS advantage in Egyptian patients with advanced HCC. Use of this drug is
      discouraged.

PMID- 24565677
TI  - Sorafenib for Egyptian patients with advanced hepatocellular carcinoma; single
      center experience.
AB  - BACKGROUND: According to the results of a number of phase 3 randomized studies,
      sorafenib is the only approved systemic therapy for advanced HCC; however the
      issue of high economic cost remains challenging; thus we have conducted this
      retrospective analysis of our HCC patients treated with sorafenib. METHODS: HCC
      patients treated at Ain Shams University Hospitals, in the period between 2010
      and 2012 were reviewed. Eligible patients were those who had received sorafenib
      for advanced HCC not eligible for or progressed after surgery or locoregional
      therapy. We investigated the impact of baseline clinicopathological factors (age,
      gender, child status, performance score, BCLC tumor stage, cause of chronic liver
      disease, median baseline alpha fetoprotein level and previous treatment received
      for HCC) on overall survival (OS) in an adjusted Cox regression model. RESULTS:
      41 patients were included in the analysis fulfilling the inclusion criteria. At a
      median follow up period of 13 months, the median PFS for the whole group was 4
      months; the median OS for the whole group is 6.25 months. Multivariate analysis
      identified three baseline characteristics that were prognostic indicators for
      overall survival: ECOG performance status (median OS for ECOG 1=7.01 months and
      for ECOG 2=3.03 months), Child-Pugh status (median OS for child A=12.04 months
      and for child B=5.23 months), and median baseline levels of alpha-fetoprotein.
      CONCLUSIONS: In limited resource countries like Egypt, we suggest that the use of
      sorafenib for the treatment of advanced HCC cases should be restricted to a
      highly selected subgroup of patients with good performance and child A.

PMID- 24565678
TI  - Basal cell hyperplasia (BCH) versus high grade prostatic intraepithelial
      neoplasia (HGPIN) in tiny prostatic needle biopsies: Unusual diagnostic dilemma.
AB  - BACKGROUND: Histopathological differentiation between BCH and HGPIN in prostatic
      needle biopsies is a diagnostic challenge. The gold standard for detection of
      HGPIN and BCH is histopathological examination; however subjectivity in
      interpretation and tiny volume of obtained tissue hamper reliable diagnosis.
      AIMS: The aim of this study was to assess usefulness of using the p63 and p504s
      to solve this problem. Although the use of p63 and p504s is now well established
      in differentiation between preneoplastic and neoplastic prostatic lesions, their
      usefulness in tiny tissue material is, however, not fully studied. METHODS: The
      study included a spectrum of 30 prostatic needle biopsies (5 BCH, 10 HGPIN, 10
      indefinite luminal proliferations where BCH and HGPIN could not be distinguished
      from each other and 5 adenocarcinomas). H&E stained sections were examined for
      histopathological features. Other sections were stained immunohistochemically
      with p63 and p504s. RESULTS: The mean age of patients was 69 (SD=7.6) years. PSA
      range was 1.3-2.7 ng/ml. Ultrasongraphic findings were unremarkable. All BCH
      showed p504s-/p63+ pattern, All HGPIN had p504s+/p63+ pattern while carcinomas
      were p504s+/p63-. After immunostaining combined with histopathological features;
      the 10 indefinite specimens could be diagnosed as 4 BCH and 6 HGPIN. The article
      explains how applying this staining pattern on the challenging specimens,
      combined with histopathological features, can be helpful in proper identification
      of prostatic proliferations.

PMID- 24565679
TI  - Age at diagnosis in women with non-metastatic breast cancer: Is it related to
      prognosis?
AB  - OBJECTIVE: Primary objective was to verify whether breast cancer patients aged
      less than 40 years at diagnosis have poorer prognosis than older patients.
      Secondary to assess prognostic factors influencing disease free survival.
      METHODS: 941 women were diagnosed with non-metastatic breast cancer at NCI, Cairo
      in 2003. Epidemiologic, clinico-pathological characteristics, treatment
      modalities and disease free survival were compared among the two age groups.
      Prognostic factors were evaluated for association with disease-free survival.
      RESULTS: One hundred-eighty-one patients (19.2%) were younger than 40 years and
      760 (80.8%) were older. Older women presented with higher rates of comorbidities
      and younger women presented with more hormone non-responsive tumors. Young women
      presented with larger tumors pT4=13.8% compared to 8.6% in older women, yet not
      significant. Young women were treated with more conservative surgery, more
      adjuvant chemotherapy and radiotherapy while older women with more radical
      mastectomies and more hormonal treatment. Recurrence rates were significantly
      higher among young women 44.2% compared to 34.5% in older women. Five year
      disease free survival in young women was 38.9% +/- 4.6% compared to 48.6% +/-
      2.5% with adjusted hazard ratio of 1.22 95% CI (0.91-1.64), p=0.19. Multivariate
      analyses identified positive axillary lymph nodes (pN2-pN3), larger tumor size
      (pT3-pT4), hypertension, lobular carcinoma type and lack of adjuvant systemic
      treatment as independent factors associated with poor DFS. CONCLUSION: Young
      women were not found to have poorer prognosis, yet they presented with more ER
      negative tumors. Most of women presented with advanced stage and young women had
      higher recurrence rates.

PMID- 24565680
TI  - Prognostic value of lymph node ratio in node-positive breast cancer in Egyptian
      patients.
AB  - BACKGROUND: Breast cancer in Egypt is the most common cancer among women and is
      the leading cause of cancer mortality. Traditionally, axillary lymph node
      involvement is considered among the most important prognostic factors in breast
      cancer. Nonetheless, accumulating evidence suggests that axillary lymph node
      ratio should be considered as an alternative to classical pN classification.
      MATERIALS AND METHODS: We performed a retrospective analysis of patients with
      operable node-positive breast cancer, to investigate the prognostic significance
      of axillary lymph node ratio. RESULTS: Five-hundred patients were considered
      eligible for the analysis. Median follow-up was 35 months (95% CI 32-37 months),
      the median disease-free survival (DFS) was 49 months (95% CI, 46.4-52.2 months).
      The classification of patients based on pN staging system failed to prognosticate
      DFS in the multivariate analysis. Conversely, grade 3 tumors, and the
      intermediate (>0.20 to <=0.65) and high (>0.65) LNR were the only variables that
      were independently associated with adverse DFS. The overall survival (OS) in this
      series was 69 months (95% CI 60-77). CONCLUSION: The analysis of outcome of
      patients with early breast cancer in Egypt identified the adverse prognostic
      effects of high tumor grade, ER negativity and intermediate and high LNR on DFS.
      If the utility of the LNR is validated in other studies, it may replace the use
      of absolute number of axillary lymph nodes.

PMID- 24565681
TI  - ERalpha and ERK1/2 MAP kinase expression in microdissected stromal and epithelial
      endometrial cells.
AB  - Our previous published data detected higher expression of total and active
      mitogen activated protein kinase (MAPK) in the epithelial vs. stromal cells of
      the endometrium. In the present work we compared the expression of ERK1/2 MAPK
      and estrogen receptor alpha (ERalpha) in epithelial versus stromal cells in
      benign human endometrial tissues. Laser capture microdissection was used to
      separate glandular epithelium and stromal cells from six frozen, proliferative
      phase endometrial specimens. Total and phosphorylated levels for ERK1/2 and
      ERalpha were measured by quantitation of signals from Western blots using
      specific antibodies against the active and total forms of ERK1/2 and against
      ERalpha. When the level of the proteins was quantitated and normalized to beta
      actin from microdissected stroma and epithelium, no significant difference was
      detected in the levels of these proteins between the two tissue compartments.
      There was a trend toward higher expression in the stroma vs. epithelium,
      respectively (active ERK1/2 0.45 +/- 0.17 vs. 0.2 +/- 0.65; total ERK1/2 0.54 +/-
      0.35 vs. 0.28 +/- 0.23; ERalpha 0.82 +/- 0.28 vs. 0.54 +/- 0.18; n=6). These data
      demonstrate that there are comparable levels of ERalpha (P=0.41), total ERK1/2
      (P=0.18) and active ERK1/2 (P=0.13) in the stroma and epithelium of proliferative
      phase endometrium with a trend toward higher expression of these proteins in the
      stromal compartment.

PMID- 24565682
TI  - Prognostic value of IDH1 mutations identified with PCR-RFLP assay in acute
      myeloid leukemia patients.
AB  - BACKGROUND: Somatic mutations in isocitrate dehydrogenase 1 (IDH1) gene occur
      frequently in primary brain tumors. Recently theses mutations were demonstrated
      in acute myeloid leukemia (AML). So far, assessment of these mutations relied on
      the DNA sequencing technique. AIM OF THE WORK: The aim of this study was to
      detect somatic mutations in IDH1 gene using mismatched primers suitable for
      endonuclease based detection, without the need for DNA sequencing, and to
      estimate its prognostic value, on patients with de novo AML. METHODS: Residual
      DNA extracted from pretreatment bone marrow (BM) samples of 100 patients with de
      novo AML was used. The polymerase chain reaction-restriction fragment length
      polymorphism method (PCR-RFLP) was adapted to IDH1gene, codon 132 mutations
      screening. RESULTS: The frequency of IDH1 mutations was 13%. In the non-acute
      promyelocytic leukemia group (non-APL), IDH1 mutations were significantly
      associated with FLT3-ITD negative patients (p=0.03). Patients with IDH1 mutations
      did not achieve complete remission (CR). There was a trend for shorter overall
      survival (OS) in patients with IDH1 mutation compared to those with wild type
      (p=0.08). CONCLUSION: IDH1 mutations are recurring genetic alterations in AML and
      they may have unfavorable impact on clinical outcome in adult AML. The PCR-RFLP
      method allows for a fast, inexpensive, and sensitive method for the detection of
      IDH1 mutations in AML.

PMID- 24565683
TI  - Primary mucinous adenocarcinoma of the renal pelvis with carcinoma in situ in the
      ureter.
AB  - Primary epithelial tumor of the renal pelvis is rare and only 100 cases are
      reported in the literature [1]. Histological examination of the tumor showed
      glands, cysts, and papillae lined by pseudostratified columnar epithelium with
      hyperchromatic nuclei. Scattered signet ring-type cells were also seen floating
      in large pools of extracellular mucin. Sections from the ureter showed a
      component of adenocarcinoma in situ. No invasive tumor was identified in ureteric
      tissue. One case was reported with carcinoma in situ of the ureter (2).
      Immunohistochemically: The tumor showed positivity for CK7, CK20, CK8/18, GATA-3,
      MSH-2, MSH-6, MLH-1, Ber-EP4, and S-100-P with focal positivity for CDX-2, weak
      positivity for PMS-2 and negativity in TTF-1 and Her-2. Molecular pathological
      analysis revealed microsatellite stability and without mutation in K-ras-gene.
      Thus, a diagnosis of mucinous adenocarcinoma of the renal pelvis with in situ
      adenocarcinoma of the ureter was made.

PMID- 24565684
TI  - [Significance of cardiovascular risk factors in persons of very advanced age:
      evidence, paradoxes and objectives].

PMID- 24565685
TI  - [Orthogeriatric activity in public hospitals of Castilla y Leon: description and
      review of the literature].
AB  - The benefits of the collaboration between orthopaedics and geriatrics in the
      management and care of elderly patients admitted with hip fracture have been
      widely demonstrated. A questionnaire was sent to all hospital geriatricians of
      Castilla y Leon in order to determine the characteristics this collaboration
      between orthopaedics and geriatrics in the public hospitals of Castilla y Leon.
      They were asked about the type of collaboration with orthopaedics in the care of
      the elderly patient admitted with hip fracture and details of the treatment of
      the complications. Most of the hospitals maintain a high level of orthogeriatric
      collaboration with geriatricians, and the geriatrician attends to most of the
      medical complications of these patients. The average hospital stay is 10 days,
      with a surgical delay of 3 days. Management of the most frequent clinical
      problems in hospitals of Castilla y Leon are detailed in this article, comparing
      them with the latest articles and current recommendations from clinical practice
      guides. 

PMID- 24565686
TI  - Utility of cell salvage in women undergoing abdominal myomectomy.
AB  - OBJECTIVE: We examined the use and cost of autologous blood cell salvage in women
      who undergo abdominal myomectomy. STUDY DESIGN: Patients who underwent abdominal
      myomectomy from 2007-2011 were identified. Use of the cell salvage system and
      reinfusion of autologous blood in women who had the system set-up were analyzed.
      Cost was examined by directly reported data. RESULTS: We identified 607 patients
      who underwent abdominal myomectomy. Four hundred twenty-five women (70%) had the
      set-up of the cell salvage system. Cell-salvaged blood was processed and
      reinfused into 85 of these subjects (20%). In a multivariable model, performance
      of myomectomy by a gynecologic-specific surgeon (odds ratio [OR], 2.14; 95%
      confidence interval [CI], 1.28-3.59), >5 myomas (OR, 2.49; 95% CI, 1.27-4.89),
      and larger uterine size statistically were associated significantly with cell
      salvage device set-up. Conversely, having a reproductive-endocrinology
      infertility specialist as the surgeon was associated with a significant reduction
      in cell-salvage system set-up (OR, 0.37; 95% CI, 0.21-0.66). For the women who
      had cell-salvage system set-up, uterine size of >15-19 weeks of gestation (OR,
      3.22; 95% CI, 1.56-8.95) or >=20 weeks of gestation (OR, 4.62; 95% CI, 1.45
      14.73), operating time of >120 minutes (OR, 3.98; 95% CI, 1.70-9.29), and
      intraoperative blood loss of >1000 mL (OR, 26.31; 95% CI, 10.49-65.99) were
      associated significantly with a higher incidence of reinfusion of cell-salvaged
      blood. CONCLUSION: The routine use of cell salvage in women who undergo abdominal
      myomectomy does not appear to be warranted. Cell-salvage set-up appears to be
      cost-effective only when reinfused, but clinical characteristics cannot predict
      accurately which women will require reinfusion of cell-salvaged blood.

PMID- 24565687
TI  - Traumatic brain injury, axonal injury and shaking in New Zealand sea lion pups.
AB  - Trauma is a common cause of death in neonatal New Zealand sea lion pups, and
      subadult male sea lions have been observed picking up and violently shaking some
      pups. In humans, axonal injury is a common result of traumatic brain injury, and
      can be due to direct trauma to axons or to ischaemic damage secondary to trauma.
      'Shaken baby syndrome', which has been described in human infants, is
      characterised by retinal and intracranial subdural haemorrhages, and has been
      associated with axonal injury to the brain, spinal cord and optic nerve. This
      study identifies mechanisms of traumatic brain injury in New Zealand sea lion
      pups, including impact injuries and shaking-type injuries, and identifies gross
      lesions of head trauma in 22/36 sea lion pups found dead at a breeding site in
      the Auckland Islands. Despite the high frequency of such gross lesions, only
      three of the pups had died of traumatic brain injury. Observational studies
      confirmed that shaking of pups occurred, but none were shown to die as a direct
      result of these shaking events. Axonal injury was evaluated in all 36 pup brains
      using beta-amyloid precursor protein immunohistochemistry. Immunoreactive axons
      were present in the brains of all pups examined including seven with vascular
      axonal injury and two with diffuse axonal injury, but the severity and pattern of
      injury was not reliably associated with death due to traumatic brain injury. No
      dead pups had the typical combination of gross lesions and immunohistochemical
      findings that would conform to descriptions of 'shaken baby syndrome'. Axonal
      injury was present in the optic nerves of most pups, irrespective of cause of
      death, but was associated with ischaemia rather than trauma. 

PMID- 24565688
TI  - Local injection of autologous bone marrow cells to regenerate muscle in patients
      with traumatic brachial plexus injury: a pilot study.
AB  - OBJECTIVES: Traumatic brachial plexus injury causes severe functional impairment
      of the arm. Elbow flexion is often affected. Nerve surgery or tendon transfers
      provide the only means to obtain improved elbow flexion. Unfortunately, the
      functionality of the arm often remains insufficient. Stem cell therapy could
      potentially improve muscle strength and avoid muscle-tendon transfer. This pilot
      study assesses the safety and regenerative potential of autologous bone marrow
      derived mononuclear cell injection in partially denervated biceps. METHODS: Nine
      brachial plexus patients with insufficient elbow flexion (i.e., partial
      denervation) received intramuscular escalating doses of autologous bone marrow
      derived mononuclear cells, combined with tendon transfers. Effect parameters
      included biceps biopsies, motor unit analysis on needle electromyography and
      computerised muscle tomography, before and after cell therapy. RESULTS: No
      adverse effects in vital signs, bone marrow aspiration sites, injection sites, or
      surgical wound were seen. After cell therapy there was a 52% decrease in muscle
      fibrosis (p = 0.01), an 80% increase in myofibre diameter (p = 0.007), a 50%
      increase in satellite cells (p = 0.045) and an 83% increase in capillary-to
      myofibre ratio (p < 0.001) was shown. CT analysis demonstrated a 48% decrease in
      mean muscle density (p = 0.009). Motor unit analysis showed a mean increase of
      36% in motor unit amplitude (p = 0.045), 22% increase in duration (p = 0.005) and
      29% increase in number of phases (p = 0.002). CONCLUSIONS: Mononuclear cell
      injection in partly denervated muscle of brachial plexus patients is safe. The
      results suggest enhanced muscle reinnervation and regeneration. Cite this
      article: Bone Joint Res 2014;3:38-47.

PMID- 24565689
TI  - Pleural effusion and sarcoidosis: an unusual combination.
AB  - Pleural involvement in sarcoidosis is uncommon and appears in several forms. To
      document the incidence and characteristics of pleural effusion in sarcoidosis
      patients, a review of the cases diagnosed in our centre between January 2001 and
      December 2012 was carried out. One hundred and ninety-five patients with
      sarcoidosis were identified; three (two men and one woman) presented with
      unilateral pleural effusion (1.5%): one in the right side and two in the left.
      Two were in stageii and one was in stageiv. The pleural fluid of the two patients
      who underwent thoracocentesis was predominantly lymphocytic. One of these
      patients presented chylothorax and the other had high CA-125levels. In general,
      these effusions are lymphocyte-rich, paucicellular, serous exudates (sometimes
      chylothorax) and contain proportionally higher levels of protein than LDH. Most
      cases are treated with corticosteroids, although it may resolve spontaneously. 

PMID- 24565690
TI  - Phenazinium dyes safranine O and phenosafranine induce self-structure in single
      stranded polyadenylic acid: structural and thermodynamic studies.
AB  - The interaction of phenazinium dyes, safranine O and phenosafranine with single
      stranded polyadenylic acid was studied using spectroscopic viscometric and
      calorimetric techniques. Both dyes bind to polyadenylic acid strongly with
      association constant of the order of 10(5)M(-1). Safranine O showed higher
      affinity over phenosafranine. The binding induced conformational changes in
      polyadenylic acid, but the extent of change was much higher with safranine O. The
      bound safranine O molecules acquired strong induced circular dichroism spectra
      compared to the weak induced circular dichroism of phenosafranine. Fluorescence
      polarization, iodide quenching, viscosity results and energy transfer from bases
      to bound dyes suggested intercalation of the dye molecules to polyadenylic acid
      structure. The binding was entropy driven in both the cases. Circular dichroism
      and optical melting studies revealed cooperative melting profiles for dye
      polyadenylic acid complexes that provided evidence for the formation of self
      structured polyadenylic acid on dye binding. This structural reorganization was
      further confirmed by differential scanning calorimetry results.

PMID- 24565691
TI  - Formation of bromate in sulfate radical based oxidation: mechanistic aspects and
      suppression by dissolved organic matter.
AB  - Sulfate radical based oxidation is discussed being a potential alternative to
      hydroxyl radical based oxidation for pollutant control in water treatment.
      However, formation of undesired by-products, has hardly been addressed in the
      current literature, which is an issue in other oxidative processes such as
      bromate formation in ozonation of bromide containing water (US-EPA and EU
      drinking water standard of bromate: 10 MUg L(-1)). Sulfate radicals react fast
      with bromide (k = 3.5 * 10(9) M(-1) s(-1)) which could also yield bromate as
      final product. The mechanism of bromate formation in aqueous solution in presence
      of sulfate radicals has been investigated in the present paper. Further
      experiments were performed in presence of humic acids and in surface water for
      investigating the relevance of bromate formation in context of pollutant control.
      The formation of bromate by sulfate radicals resembles the well described
      mechanism of the hydroxyl radical based bromate formation. In both cases
      hypobromous acid is a requisite intermediate. In presence of organic matter
      formation of bromate is effectively suppressed. That can be explained by
      formation of superoxide formed in the reaction of sulfate radicals plus aromatic
      moieties of organic matter, since superoxide reduces hypobromous acid yielding
      bromine atoms and bromide. Hence formation of bromate can be neglected in sulfate
      radical based oxidation at typical conditions of water treatment.

PMID- 24565692
TI  - Cellular responses in Bacillus thuringiensis CS33 during bacteriophage BtCS33
      infection.
AB  - Bacillus thuringiensis (Bt) has been widely used for 50years as a biopesticide
      for controlling insect pests. However, bacteriophage infection can cause failures
      in 50%-80% of the batches during Bt fermentation, resulting in severe losses. In
      the present work, the physiological and biochemical impacts of Bt strain CS33
      have been studied during bacteriophage infection. This study adopted a gel-based
      proteomics approach to probe the sequential changed proteins in phage-infected Bt
      cells. To phage, it depressed the host energy metabolism by suppressing the
      respiration chain, the TCA cycle, and the utilization of PHB on one hand; on the
      other hand, it hijacked the host translational machine for its own macromolecular
      synthesis. To host, superinfection exclusion might be triggered by the changes of
      S-layer protein and flagella related proteins, which were located on the cell
      surface and might play as the candidates for the phage recognition. More
      importantly, the growth rate, cell mass, and ICPs yield were significantly
      decreased. The low yield of ICPs was mainly due to the suppressed utilization of
      PHB granules. Further functional study on these altered proteins may lead to a
      better understanding of the pathogenic mechanisms and the identification of new
      targets for phage control. BIOLOGICAL SIGNIFICANCE: B. thuringiensis (Bt) has
      been widely used for 50years as a safe biopesticide for controlling agricultural
      and sanitary insect pests. However, bacteriophage infection can cause severe
      losses during B. thuringiensis fermentation. The processes and consequences of
      interactions between bacteriophage and Bt were still poorly understood, and the
      molecular mechanisms involved were more unknown. This study adopted a gel-based
      proteomics approach to probe the physiological and biochemical impacts of Bt
      strain CS33 after phage-infection. The interactions between phage BtCS33 and its
      host Bt strain CS33 occurred mainly on four aspects. First, phage synthesized its
      nucleic acids through metabolic regulation by increasing the amount of NDK.
      Second, it is reasonable to infer that a phage resistance or superinfection
      exclusion was triggered by several increased or decreased proteins (SLP, FliD,
      FlaB), which were located on the cell surface and might play as candidates for
      the phage recognition. Third, combining the decreased flavoproteins (SdhA and
      EtfB) and the down regulated Fe-S cluster biosynthesis pathway together, it can
      be suggested that the respiration chain was weakened after phage infection.
      Additionally, three key enzymes (AcnB, FumC and AdhA) involved in the TCA cycle
      were all decreased, indicating the TCA cycle was seriously inhibited after
      infection. Fourth, the growth rate, cell mass and ICPs yield of the host were
      significantly decreased. To the best of our knowledge, this work represents the
      first systematic study on the interactions of an insecticidal bacterium with its
      phage, and has contributed novel information to understand the molecular events
      in the important biological pesticide producer, B. thuringiensis, in response to
      phage challenge.

PMID- 24565693
TI  - Protective role of the mitochondrial Lon protease 1 in ochratoxin A-induced
      cytotoxicity in HEK293 cells.
AB  - Ochratoxin A (OTA) is a common kind of mycotoxin and food contaminant, which has
      various toxicological effects, especially nephrotoxicity. Our previous work about
      OTA-induced renal cytotoxicity indicated that mitochondrial Lon Protease 1
      (Lonp1) might play a protective role. Lonp1 is a multifunctional ATP-dependent
      protease which mainly participates in mitochondrial proteolysis and protein
      quality control. The study aimed at probing how Lonp1 functioned in OTA-induced
      renal cytotoxicity. By means of RNA interference, we down-regulated the
      expression of Lonp1 in HEK293 cells. Cell viability results revealed that cells
      with Lonp1 deficiency were more vulnerable to OTA. Then we identified
      differentially expressed proteins between Lonp1 knock-down cells and scrambled
      control both in the absence and presence of OTA, using iTRAQ-based quantitative
      proteomics approach. Thirty-four proteins were differentially expressed as a
      result of Lonp1 deficiency, while forty-four proteins were differentially
      expressed in response to both Lonp1 deficiency and OTA treatment. By function
      summary and pathway analysis, we presumed that Lonp1 realized its protective
      function in the resistance to OTA-induced renal cytotoxicity via 4 processes:
      defensing against OTA-induced oxidative stress in the mitochondria; regulating
      protein synthesis, modification and repair; maintaining the balance of
      carbohydrate metabolism; and assisting in mtDNA maintenance. BIOLOGICAL
      SIGNIFICANCE: OTA is a kind of mycotoxin that seriously threatens human health
      and has various toxicological effects. However, the mechanisms of its toxicity
      have not been exactly elucidated yet. The method of combination of RNAi and iTRAQ
      based quantitative proteomics paves the way to gain a better understanding of the
      toxicity mechanisms of OTA. The present study, for the first time, verified the
      protective role of Lonp1 in OTA-induced renal cytotoxicity and clarified the
      defensive mechanism. Proteomic changes in Lonp1 deficient cells induced by OTA
      added new knowledge to OTA cytotoxicity.

PMID- 24565694
TI  - Differential expression and glycosylation of proteins in the rat ileal epithelium
      in response to Echinostoma caproni infection.
AB  - Echinostoma caproni (Trematoda: Echinostomatidae) is an intestinal trematode that
      has been used as experimental model to investigate the factors determining the
      expulsion of intestinal helminths. We analyze the changes in the protein
      expression and glycosylation induced by E. caproni in Wistar rat, a host of low
      compatibility in which the parasites are rapidly rejected. To determine the
      changes in protein expression, two-dimensional difference gel electrophoresis was
      employed using protein extracts from the intestine of naive and infected rats.
      The patterns of glycosylation were analyzed by lectin blotting. Those spots
      showing differential expression or glycosylation were analyzed by mass
      spectrometry. A total of 33 protein spots differentially expressed were
      identified (26 were found to be over-expressed and 7 down-regulated). Moreover,
      E. caproni induced changes in the glycosylation status of 8 proteins that were
      successfully identified. Most of these proteins were related to the cytoskeleton
      and the maintenance of the functional integrity of the ileal epithelium. This
      suggests that the regeneration of the intestinal tissue is a major effector
      mechanism responsible for the early expulsion of this helminth. Furthermore,
      several proteins involved in the energy metabolism were also altered in the ileum
      of rats as a consequence of the E. caproni infection. BIOLOGICAL SIGNIFICANCE:
      Our analysis provides essential new insights in the factors determining the
      natural expulsion of intestinal parasitic helminths from their hosts. The results
      obtained contribute to a better understanding of the effective mechanisms
      involved in the defense against the intestinal helminths. The identification of
      proteins in the intestine that become modified in their expression or
      glycosylation in hosts in which the parasite is rapidly rejected may serve for
      the development of tools for the control of these infections.

PMID- 24565695
TI  - Improving the identification rate of data independent label-free quantitative
      proteomics experiments on non-model crops: a case study on apple fruit.
AB  - Complex peptide extracts from non-model crops are troublesome for proper
      identification and quantification. To increase the identification rate of label
      free DIA experiments of Braeburn apple a new workflow was developed where a DDA
      database was constructed and linked to the DIA data. At a first level, parent
      masses found in DIA were searched in the DDA database based on their mass to
      charge ratio and retention time; at a second level, masses of fragmentation ions
      were compared for each of the linked spectrum. Following this workflow, a tenfold
      increase of peptides was identified from a single DIA run. As proof of principle,
      the designed workflow was applied to determine the changes during a storage
      experiment, achieving a two-fold identification increase in the number of
      significant peptides. The corresponding protein families were divided into nine
      clusters, representing different time profiles of changes in abundances during
      storage. Up-regulated protein families already show a glimpse of important
      pathways affecting aging during long-term storage, such as ethylene synthesis,
      and responses to abiotic stresses and their influence on the central metabolism.
      BIOLOGICAL SIGNIFICANCE: Proteomics research on non-model crops causes additional
      difficulties in identifying the peptides present in, often complex, samples. This
      work proposes a new workflow to retrieve more identifications from a set of
      quantitative data, based on linking DIA and DDA data at two consecutive levels.
      As proof of principle, a storage experiment on Braeburn apple resulted in twice
      as much identified storage related peptides. Important proteins involved in
      central metabolism and stress are significantly up-regulated after long term
      storage. This article is part of a Special Issue entitled: Proteomics of non
      model organisms.

PMID- 24565696
TI  - Multiple information sources and consequences of conflicting information about
      medicine use during pregnancy: a multinational Internet-based survey.
AB  - BACKGROUND: A wide variety of information sources on medicines is available for
      pregnant women. When using multiple information sources, there is the risk that
      information will vary or even conflict. OBJECTIVE: The objective of this
      multinational study was to analyze the extent to which pregnant women use
      multiple information sources and the consequences of conflicting information, and
      to investigate which maternal sociodemographic, lifestyle, and medical factors
      were associated with these objectives. METHODS: An anonymous Internet-based
      questionnaire was made accessible during a period of 2 months, on 1 to 4 Internet
      websites used by pregnant women in 5 regions (Eastern Europe, Western Europe,
      Northern Europe, Americas, Australia). A total of 7092 responses were obtained
      (n=5090 pregnant women; n=2002 women with a child younger than 25 weeks).
      Descriptive statistics and logistic regression analysis were used. RESULTS: Of
      the respondents who stated that they needed information, 16.16% (655/4054) used
      one information source and 83.69% (3393/4054) used multiple information sources.
      Of respondents who used more than one information source, 22.62% (759/3355)
      stated that the information was conflicted. According to multivariate logistic
      regression analysis, factors significantly associated with experiencing conflict
      in medicine information included being a mother (OR 1.32, 95% CI 1.11-1.58),
      having university (OR 1.33, 95% CI 1.09-1.63) or other education (OR 1.49, 95% CI
      1.09-2.03), residing in Eastern Europe (OR 1.52, 95% CI 1.22-1.89) or Australia
      (OR 2.28, 95% CI 1.42-3.67), use of 3 (OR 1.29, 95% CI 1.04-1.60) or >4
      information sources (OR 1.82, 95% CI 1.49-2.23), and having >=2 chronic diseases
      (OR 1.49, 95% CI 1.18-1.89). Because of conflicting information, 43.61% (331/759)
      decided not to use medication during pregnancy, 30.30% (230/759) sought a new
      information source, 32.67% (248/759) chose to rely on one source and ignore the
      conflicting one, 25.03% (190/759) became anxious, and 2.64% (20/759) did nothing.
      Factors significantly associated with not using medication as a consequence of
      conflicting information were being pregnant (OR 1.75, 95% CI 1.28-2.41) or
      experiencing 3-4 health disorders (OR 1.99, 95% CI 1.10-3.58). Women with no
      chronic diseases were more likely not to take medicines than women with >=2
      chronic diseases (OR 2.22, 95% CI 1.47-3.45). Factors significantly associated
      with becoming anxious were >4 information sources (OR 2.67, 95% CI 1.70-4.18) and
      residing in Eastern Europe (OR 0.57, 95% CI 0.36-0.90). CONCLUSIONS: Almost all
      the pregnant women used multiple information sources when seeking information on
      taking medicines during pregnancy and one-fifth obtained conflicting information,
      leading to anxiety and the decision not to use the medication. Regional,
      educational, and chronic disease characteristics were associated with
      experiencing conflicting information and influenced the decision not to use
      medication or increased anxiety. Accurate and uniform teratology information
      should be made more available to the public.

PMID- 24565697
TI  - Outcomes of patients with metastatic renal cell carcinoma and end-stage renal
      disease receiving dialysis and targeted therapies: a single institution
      experience.
AB  - INTRODUCTION: Limited data are available regarding patients with renal cell
      carcinoma and ESRD treated with TTs. The objective of this study was to explore
      the tolerability and safety of TT in patients with mRCC and ESRD. PATIENTS AND
      METHODS: We retrospectively identified patients with mRCC and ESRD treated at the
      University of Texas M.D. Anderson Cancer Center from 2002 to 2012. Patient
      characteristics including demographic, histology, treatment, and adverse events
      are reported. Duration of treatment (TOT) was determined from date of drug
      initiation to discontinuation. Overall survival (OS) was determined from
      initiation of TT to death. Statistics are descriptive. RESULTS: Fourteen patients
      were identified. Ten patients had clear-cell histology and 4 had papillary
      histology. The median number of TTs per patient was 3 (range, 1-4) with median
      TOT of 28 months for all TTs. Eighty-eight percent of all toxicities were Grade 1
      to 2; no Grade 4 toxicities were noted. Treatment discontinuations included 3
      patients treated with sorafenib due to hand-foot syndrome, intolerable fatigue,
      and squamous cell skin cancer development; 2 patients treated with pazopanib due
      to intolerable fatigue and increased transaminase levels; and 1 patient treated
      with everolimus due to pneumonitis. Eight patients died from progressive disease.
      Median OS from initiation of TT was 28.5 months and 35 months from time of
      diagnosis. CONCLUSION: Toxicities were mild to moderate and consistent with those
      reported in previous studies. TTs appear to be safe, well tolerated and produce
      antitumor response in patients with mRCC and ESRD receiving dialysis.

PMID- 24565699
TI  - PKC-mediated HuD-GAP43 pathway activation in a mouse model of antiretroviral
      painful neuropathy.
AB  - Patients treated with nucleoside reverse transcriptase inhibitors (NRTIs) develop
      painful neuropathies that lead to discontinuation of antiretroviral therapy thus
      limiting viral suppression strategies. The mechanisms by which NRTIs contribute
      to the development of neuropathy are not known. In order to elucidate the
      mechanisms underlying this drug-induced neuropathy, we have characterized
      cellular events in the central nervous system following antiretroviral treatment.
      Systemic administration of the antiretroviral agent, 2',3'-dideoxycytidine (ddC)
      considerably increased the expression and phosphorylation of protein kinase C
      (PKC) gamma and E, enzymes highly involved in pain processes, within
      periaqueductal grey matter (PAG), and, to a lesser extent, within thalamus and
      prefrontal cortex. These events appeared in coincidence with thermal and
      mechanical allodynia, but PKC blockade did not prevent the antiretroviral-induced
      pain hypersensitivity, ruling out a major involvement of PKC in the ddC-induced
      nociceptive behaviour. An increased expression of GAP43, a marker of
      neuroregeneration, and decreased levels of ATF3, a marker of neuroregeneration,
      were detected in all brain areas. ddC treatment also increased the expression of
      HuD, a RNA-binding protein target of PKC known to stabilize GAP43 mRNA.
      Pharmacological blockade of PKC prevented HuD and GAP43 overexpression. Silencing
      of both PKCgamma and HuD reduced GAP43 levels in control mice and prevented the
      ddC-induced GAP43 enhanced expression. Present findings illustrate the presence
      of a supraspinal PKC-mediated HuD-GAP43 pathway activated by ddC. Based on our
      results, we speculate that antiretroviral drugs may recruit the HuD-GAP43
      pathway, potentially contributing to a response to the antiretroviral neuronal
      toxicity. 

PMID- 24565700
TI  - The variable in common variable immunodeficiency: a disease of complex
      phenotypes.
AB  - Common variable immunodeficiency (CVID) is the most common and clinically most
      important severe primary antibody deficiency and is characterized by low levels
      of IgG, IgA, and/or IgM, with a failure to produce specific antibodies. This
      diagnostic category represents a heterogeneous group of disorders, which present
      not only with acute and chronic infections but also with a range of inflammatory
      and autoimmune disorders as well as an increased incidence of lymphoma and other
      malignancies. Patients can now be categorized into distinct clinical phenotypes
      based on analysis of large cohort studies and be further stratified by
      immunologic laboratory testing. The biologic importance of this categorization is
      made clear by the 11-fold increase in mortality if even one of these phenotypes
      (cytopenias, lymphoproliferation, or enteropathy) is present. Limited progress in
      defining the underlying molecular causes has been made with known causative
      single gene defects accounting for only 3% of cases, and, for this and the
      reasons mentioned above, CVID remains resolute in its variability. This review
      provides a practical approach to risk stratification of these complex phenotypes
      by using current clinical categories and laboratory biomarkers. The effects of
      infection as well as inflammatory and autoimmune complications on different organ
      systems are discussed alongside strategies to reduce diagnostic delay. Recent
      developments in diagnostics and therapy are also explored. 

PMID- 24565698
TI  - Autologous mesenchymal stem cells produce concordant improvements in regional
      function, tissue perfusion, and fibrotic burden when administered to patients
      undergoing coronary artery bypass grafting: The Prospective Randomized Study of
      Mesenchymal Stem Cell Therapy in Patients Undergoing Cardiac Surgery (PROMETHEUS)
      trial.
AB  - RATIONALE: Although accumulating data support the efficacy of intramyocardial
      cell-based therapy to improve left ventricular (LV) function in patients with
      chronic ischemic cardiomyopathy undergoing CABG, the underlying mechanism and
      impact of cell injection site remain controversial. Mesenchymal stem cells (MSCs)
      improve LV structure and function through several effects including reducing
      fibrosis, neoangiogenesis, and neomyogenesis. OBJECTIVE: To test the hypothesis
      that the impact on cardiac structure and function after intramyocardial
      injections of autologous MSCs results from a concordance of prorecovery
      phenotypic effects. METHODS AND RESULTS: Six patients were injected with
      autologous MSCs into akinetic/hypokinetic myocardial territories not receiving
      bypass graft for clinical reasons. MRI was used to measure scar, perfusion, wall
      thickness, and contractility at baseline, at 3, 6, and 18 months and to compare
      structural and functional recovery in regions that received MSC injections alone,
      revascularization alone, or neither. A composite score of MRI variables was used
      to assess concordance of antifibrotic effects, perfusion, and contraction at
      different regions. After 18 months, subjects receiving MSCs exhibited increased
      LV ejection fraction (+9.4 +/- 1.7%, P=0.0002) and decreased scar mass (-47.5 +/-
      8.1%; P<0.0001) compared with baseline. MSC-injected segments had concordant
      reduction in scar size, perfusion, and contractile improvement (concordant score:
      2.93 +/- 0.07), whereas revascularized (0.5 +/- 0.21) and nontreated segments (
      0.07 +/- 0.34) demonstrated nonconcordant changes (P<0.0001 versus injected
      segments). CONCLUSIONS: Intramyocardial injection of autologous MSCs into
      akinetic yet nonrevascularized segments produces comprehensive regional
      functional restitution, which in turn drives improvement in global LV function.
      These findings, although inconclusive because of lack of placebo group, have
      important therapeutic and mechanistic hypothesis-generating implications.
      CLINICAL TRIAL REGISTRATION URL: http://clinicaltrials.gov/show/NCT00587990.
      Unique identifier: NCT00587990.

PMID- 24565702
TI  - Should therapeutic immunoglobulin be considered a generic product? An evidence
      based approach.
AB  - The increasing therapeutic use of intravenous immunoglobulin (IVIG) for an
      expanding range of indications, from immunodeficiency to autoimmune disease
      coupled with the availability of multiple products has prompted debate on whether
      IVIG products should be considered to be generic. Although the manufacturing
      process and associated excipients for individual products varies, all currently
      licensed IVIG products are composed predominantly of IgG (>95%) and comply with
      the quality standards of regulatory agencies. Because these products have a
      licence for a common group of indications, does that mean that all of them are
      equally efficacious in the treatment of the same disease? In vitro data and
      published evidence of head-to-head trials of IVIG in primary antibody deficiency,
      immune thrombocytopenic purpura, and chronic inflammatory demyelinating
      polyneuropathy suggest that different IVIG products are likely to be equally
      efficacious in terms of clinical efficacy. Consequently, it would be reasonable
      to consider IVIG products to be generic in terms of clinical outcomes. However,
      the lack of significant differences in clinical efficacy should not be used to
      justify frequent product changes on financial or nonclinical grounds because of
      the increased risk of adverse effects and difficulty in tracking a suspect
      product in the event of a future outbreak of IVIG-associated viral transmission. 

PMID- 24565701
TI  - Adverse effects of IgG therapy.
AB  - IgG is widely used for patients with immune deficiencies and in a broad range of
      autoimmune and inflammatory disorders. Up to 40% of intravenous infusions of IgG
      may be associated with adverse effects (AEs), which are mostly uncomfortable or
      unpleasant but often are not serious. The most common infusion-related AE is
      headache. More serious reactions, including true anaphylaxis and anaphylactoid
      reactions, occur less frequently. Most reactions are related to the rate of
      infusion and can be prevented or treated just by slowing the infusion rate.
      Medications such as nonsteroidal anti-inflammatory drugs, antihistamines, or
      corticosteroids also may be helpful in preventing or treating these common AEs.
      IgA deficiency with the potential of IgG or IgE antibodies against IgA increases
      the risk of some AEs but should not be viewed as a contraindication if IgG
      therapy is needed. Potentially serious AEs include renal dysfunction and/or
      failure, thromboembolic events, and acute hemolysis. These events usually are
      multifactorial, related to combinations of constituents in the IgG product as
      well as risk factors for the recipient. Awareness of these factors should allow
      minimization of the risks and consequences of these AEs. Subcutaneous IgG is
      absorbed more slowly into the circulation and has a lower incidence of AEs, but
      awareness and diligence are necessary whenever IgG is administered. 

PMID- 24565703
TI  - Antibiotic prophylaxis in primary immune deficiency disorders.
AB  - Long-term prophylactic antibiotics are being widely implemented as primary or
      adjunctive therapy in primary immune deficiencies. This practice has transformed
      clinical outcomes in the setting of chronic granulomatous disease, complement
      deficiencies, Mendelian susceptibility to mycobacterial disease, Wiskott-Aldrich
      syndrome, hyper-IgE syndrome, Toll signaling defects, and prevented Pneumocystis
      in patients with T-cell deficiencies. Yet, controlled trials are few in the
      context of primary antibody deficiency syndromes, and most of this practice has
      been extrapolated from data in patients who are immune competent and with
      recurrent acute otitis media, chronic rhinosinusitis, cystic fibrosis, and
      bronchiectasis. The paucity of guidelines on the subject is reflected in recent
      surveys among practicing immunologists that highlight differences of habit
      regarding this treatment. Such discrepancies reinforce the lack of standard
      protocols on the subject. This review will provide evidence for the use of
      antibiotic prophylaxis in various primary immune deficiency populations,
      especially highlighting the role antibiotic prophylaxis in primary antibody
      deficiency syndromes. We also discussed the relationship of long-term antibiotic
      use and the prevalence of resistant pathogens. Overall, examination of available
      data on the use of prophylactic antibiotics in antibody deficiency syndromes
      merit future investigation in well-designed multicenter prospective trials
      because this population has few other management options. 

PMID- 24565704
TI  - Thoracic duct injury resulting in abnormal newborn screen.
AB  - Measurement of T-cell receptor excision circles (TREC) in neonates has allowed
      for population-based screening of severe combined immunodeficiency and other
      disorders associated with T-cell lymphopenia. In addition to primary T-cell
      lymphopenic disorders, secondary causes of T-cell lymphopenia can be diagnosed
      with TREC analysis. We discuss the diagnostic evaluation of a patient with normal
      TREC analysis at birth that became abnormal after cardiac surgery. TREC analysis
      was performed by the Florida State Laboratory. Diagnostic evaluation and
      treatment were performed at All Children's Hospital, St Petersburg, Florida. We
      identified a 38-day-old female patient with thoracic duct injury, which caused
      chylothorax and chylous ascites diagnosed after an abnormal newborn screen.
      Chylothorax was secondary to thoracic duct injury after cardiac surgery and led
      to severe lymphopenia and hypogammaglobulinemia. Thoracic duct ligation led to
      improved lymphocyte counts and normalization of immunoglobulin levels. Secondary
      causes of lymphopenia are detected with TREC assay that lead to abnormal newborn
      screen results. Many secondary causes of lymphopenia can be acquired with normal
      initial newborn screens that become abnormal over time. 

PMID- 24565705
TI  - The diverse clinical features of chromosome 22q11.2 deletion syndrome (DiGeorge
      syndrome).
AB  - A 2-year-old boy with chromosome 22q11.2 deletion syndrome was referred for
      recurrent sinopulmonary infections. He was diagnosed shortly after birth by a
      fluorescence in situ hybridization test that was performed due to interrupted
      aortic arch type B. He had no hypocalcemia, and his recovery from cardiac repair
      was uneventful. He had difficulty feeding and gained weight slowly, but,
      otherwise, there were no concerns during his first year of life. At 15 months of
      age, he began to develop significant otitis media and bronchitis. He was
      hospitalized once for pneumonia at 18 months of age and has never been off
      antibiotics for more than 1 week since then. He has not had any previous
      immunologic evaluation. Recurrent sinopulmonary infections in a child with
      chromosome 22q11.2 deletion syndrome can have the same etiologies as in any other
      child. Atopy, anatomic issues, cystic fibrosis, and new environmental exposures
      could be considered in this setting. Early childhood can be problematic for
      patients with chromosome 22q11.2 deletion syndrome due to unfavorable drainage of
      the middle ear and sinuses. Atopy occurs at a higher frequency in 22q11.2
      deletion syndrome, and these children also have a higher rate of gastroesophageal
      reflux and aspiration than the general population. As would be appropriate for
      any child who presents with recurrent infections at 2 years of age, an
      immunologic evaluation should be performed. In this review, we will highlight
      recent findings and new data on the management of children and adults with
      chromosome 22q11.2 deletion syndrome. 

PMID- 24565707
TI  - Physician compliance with updated practice parameters for influenza vaccination
      in individuals with egg allergies.
AB  - BACKGROUND: Significant recent changes to the recommendations in providing
      trivalent seasonal influenza vaccine (TIV) to individuals with egg allergy were
      made, but their implementation has not been studied. OBJECTIVES: To investigate
      allergist-reported compliance with updated TIV administration guidelines for
      individuals with egg allergy. METHODS: A 22-question electronic survey was
      distributed via e-mail to American Academy of Allergy, Asthma, and Immunology
      members (allergists), which queried practice styles and attitudes that pertain to
      TIV administration to individuals with egg allergy. RESULTS: Only 1% of 895
      respondents believed that TIV should be contraindicated for individuals with egg
      allergy, 3.8% reported not administering TIV to individuals with egg allergy, and
      17% reported only administering TIV to individuals with mild egg allergy; 13.2%
      reported that risk-mitigating precautions (eg, vaccine skin testing, graded-dose
      challenges) were necessary. Postimplementation change compared with
      preimplementation change included less intradermal testing (30.6% vs 64.9%), less
      multistep desensitization (34.7% vs 65.3%), observing more patients for >30
      minutes after vaccination (79.1% vs 20.9%), administering TIV despite positive
      TIV skin tests (65.4% vs 34.6%) (all P < .001), but no significant reduction in
      performing TIV prick skin testing (46.2% vs 53.8%). Factors associated with not
      performing TIV skin testing included reading the guidelines (P = .028), academic
      practice (P < .01), and fewer years in practice (P < .01). Only 48.6% agreed that
      TIV can safely be administered in the primary care setting to individuals with
      egg allergy, and only 41.9% advised their patients accordingly. CONCLUSION: There
      were significant shifts in practice style over time concurrent with newly
      established guidelines, except for vaccine skin testing. Physician opinions are
      also concurrent with guideline changes. Although TIV administration guideline
      recommendations are being successfully implemented, greater adherence should be
      promoted.

PMID- 24565706
TI  - Food-induced anaphylaxis among commercially insured US adults: patient
      concordance with postdischarge care guidelines.
AB  - BACKGROUND: Food-induced anaphylaxis is a potentially life-threatening condition
      that frequently results in emergency department (ED) visits and/or
      hospitalization. Little information is available on patient compliance with
      recommended postdischarge anaphylaxis care. OBJECTIVE: To describe patient
      characteristics, concordance with recommended postdischarge care, and risk of
      repeated events among adults with an initial ED visit and/or hospitalization for
      food-induced anaphylaxis. METHODS: In this retrospective study of health care
      claims, adults with an ED visit and/or hospitalization for food-induced
      anaphylaxis were identified from the 2002-2008 Truven Health MarketScan Databases
      by using an expanded International Classification of Diseases, Ninth Revision,
      Clinical Modification diagnosis code algorithm. The first identified ED visit
      and/or hospitalization was the index event. Data from patients with continuous
      medical and prescription coverage for >=1 year before and after the index event
      were retained for analysis. Analyses included baseline demographic and clinical
      characteristics, postdischarge epinephrine autoinjector (EAI) prescription fills
      and allergist/immunologist visits, and repeated events in the 1-year postindex
      period. RESULTS: Patients (n = 1370) had a mean (SD) age of 44 +/- 15 years, 58%
      were women. Most (86%) were seen in the ED and/ discharged from the ED. Within 1
      year after discharge, 54% of adults had filled >=1 EAI prescription (71% within 1
      week) and 22% had >=1 allergist/immunologist visit (53% within 4 weeks). Overall,
      73 patients (5%) had evidence of a subsequent anaphylaxis-related ED visit and/or
      hospitalization 1 year after discharge. CONCLUSION: Concordance with recommended
      postdischarge anaphylaxis care was low among adults with food-induced
      anaphylaxis. Within 1 year after discharge, 54% of patients filled an EAI
      prescription and 22% consulted an allergist/immunologist.

PMID- 24565708
TI  - High-fidelity hybrid simulation of allergic emergencies demonstrates improved
      preparedness for office emergencies in pediatric allergy clinics.
AB  - BACKGROUND: Simulation models that used high-fidelity mannequins have shown
      promise in medical education, particularly for cases in which the event is
      uncommon. Allergy physicians encounter emergencies in their offices, and these
      can be the source of much trepidation. OBJECTIVE: To determine if case-based
      simulations with high-fidelity mannequins are effective in teaching and retention
      of emergency management team skills. METHODS: Allergy clinics were invited to
      Arkansas Children's Hospital Pediatric Understanding and Learning through
      Simulation Education center for a 1-day workshop to evaluate skills concerning
      the management of allergic emergencies. A Clinical Emergency Preparedness Team
      Performance Evaluation was developed to evaluate the competence of teams in
      several areas: leadership and/or role clarity, closed-loop communication, team
      support, situational awareness, and scenario-specific skills. Four cases, which
      focus on common allergic emergencies, were simulated by using high-fidelity
      mannequins and standardized patients. Teams were evaluated by multiple reviewers
      by using video recording and standardized scoring. Ten to 12 months after initial
      training, an unannounced in situ case was performed to determine retention of the
      skills training. RESULTS: Clinics showed significant improvements for role
      clarity, teamwork, situational awareness, and scenario-specific skills during the
      1-day workshop (all P < .003). Follow-up in situ scenarios 10-12 months later
      demonstrated retention of skills training at both clinics (all P <= .004).
      CONCLUSION: Clinical Emergency Preparedness Team Performance Evaluation scores
      demonstrated improved team management skills with simulation training in office
      emergencies. Significant recall of team emergency management skills was
      demonstrated months after the initial training.

PMID- 24565709
TI  - Overweight/obesity and risk of seasonal asthma exacerbations.
AB  - BACKGROUND: Obesity is associated with an increased risk for asthma
      exacerbations, but whether this risk is related to the season of exacerbation is
      not known. OBJECTIVE: To determine the relationship of increased body mass index
      (BMI) to the season of asthma exacerbation. METHODS: Study subjects were adult
      (aged 18-65 years) and children (aged 5-17 years) health plan members with
      persistent asthma in 2008 for whom a BMI measurement was available. BMI
      categories were normal (<25 kg/m(2)), overweight (25-29.9 kg/m(2)), and obese
      (>=30 kg/m(2)). Exacerbations were defined as oral corticosteroid dispensings
      linked to an asthma encounter in the spring, summer, fall, or winter of 2009.
      RESULTS: The cohort included 17,316 adults and 10,700 children. There was a
      significant (P < .05) linear increase with BMI category in the proportion of
      adults with exacerbations in every season and in the proportion of children with
      exacerbations during fall and winter. Relationships of overweight or obesity (vs
      normal weight) to fall and winter exacerbations remained significant in both
      adults and children after adjustment for sex and education. In a generalized
      estimating equation model, both BMI status and season (spring, fall, and winter)
      were related to exacerbations. Moreover, we noted a significant interaction in
      adults (P = .03) but not children (P = .97) of the BMI-exacerbation association
      by season (fall-winter vs spring-summer). CONCLUSION: Higher BMI values increased
      the risk for asthma exacerbations in adults and children with persistent asthma,
      particularly for fall-winter exacerbations in adults. Potential mechanisms for
      these findings, including vitamin D status, viral infections, and corticosteroid
      responsiveness, merit further study.

PMID- 24565710
TI  - Clinical characterization and IgE profiling of birch (Betula verrucosa)--allergic
      individuals suffering from allergic reactions to raw fruits and vegetables.
AB  - BACKGROUND: Hypersensitivity to raw fruits and vegetables is often associated
      with respiratory allergy to birch (Betula verrucosa) pollen and is considered to
      be the most prevalent form of food allergy in adults sensitized to birch pollen.
      OBJECTIVE: The aim of the study was to investigate the association of clinical
      allergy and IgE profiles in individuals with birch pollen allergy and
      hypersensitivity to raw fruits and vegetables. METHODS: A total of 59 adults with
      clinical and skin prick test confirmed birch pollen allergy were included in the
      study. All the subjects were interviewed by using a structured questionnaire and
      were examined in vivo by the open test, with the appropriate fruits and
      vegetables. ImmunoCAP and ImmunoCAP ISAC were used as in vitro diagnostics to
      assess sensitization profiles for each individual, and principal components
      analysis was used to analyze the IgE data sets. RESULTS: Of 59 individuals, 54
      (92%) had positive prick-prick test with raw potato, carrot, apple, and/or
      hazelnut, and the skin prick test was always positive when the corresponding skin
      challenge was defined as positive. Specific IgE in the ImmunoCAP and inhibition
      assays with rMal d 1 and rBet v 1 demonstrated that Bet v 1 is driving the
      sensitization against pathogenesis related-10 proteins. However, positive IgE in
      vitro results could not be used to predict clinical reactivity to raw fruits and
      vegetables. CONCLUSIONS: The present study showed that component-based IgE
      profiling does not enhance the diagnostic potential in case of pollen-food
      syndrome, which may be associated with other as yet unidentified components.

PMID- 24565711
TI  - Ara h 2 is the best predictor for peanut allergy in adults.
AB  - BACKGROUND: Specific IgE (sIgE) to Ara h 2 as a clinical predictor for peanut
      allergy in children has a diagnostic value comparable with a prediction model
      that contains sex, skin prick test (SPT), sIgE to peanut extract, and total IgE
      minus sIgE. In adults, the diagnostic value of peanut components has not yet been
      studied. OBJECTIVE: To validate a pediatric prediction model in an adult
      population; to define the diagnostic value of sIgE to peanut components. METHODS:
      Validation was performed by discrimination with an area under the receiver
      operating characteristic curve (AUC) and calibration with the Hosmer-Lemeshow
      test. The diagnostic value of the peanut components was assessed with the AUC.
      RESULTS: Validation of the pediatric model in 94 adults showed poor
      discrimination (AUC, 0.64) but good calibration (P = .48); sIgE to Ara h 2 was
      the best diagnostic predictor (AUC, 0.76). By using a cutoff value with a 100%
      positive predictive value (>=1.75 kU/L), 28% of patients could be diagnosed with
      100% accuracy. The highest negative predictive value was 63%. A higher negative
      predictive value could not be calculated for any other test. Although sIgE to Ara
      h 2 was significantly correlated with severity, it did not discriminate between
      mild and severe allergy in individual patients (AUC < 0.65). CONCLUSION: sIgE to
      Ara h 2 has the best discriminative ability of all diagnostic tests. It can
      accurately diagnose peanut allergy in 28% of patients but cannot be used to
      exclude a peanut allergy in an adult population.

PMID- 24565712
TI  - Anti-inflammatory treatment of atopic asthma guided by exhaled nitric oxide: a
      randomized, controlled trial.
AB  - BACKGROUND: Atopic asthma is characterized by Th2 cytokine-driven inflammation of
      the airway mucosa, which is signaled by the fraction of exhaled nitric oxide
      (FENO). OBJECTIVE: We tested whether an FENO-guided anti-inflammatory treatment
      algorithm could improve asthma-related quality of life and asthma symptom
      control, and reduce exacerbations in atopic asthmatics within primary care.
      METHODS: Altogether, 187 patients with asthma and who were nonsmokers (age range,
      18-64 years) with perennial allergy and who were on regular inhaled
      corticosteroid treatment were recruited at 17 primary health care centers,
      randomly assigned to 2 groups and followed up for 1 year. For the controls (n =
      88), FENO measurement was blinded to both operator and patient, and anti
      inflammatory treatment was adjusted according to usual care. In the active group
      (n = 93), treatment was adjusted according to FENO. Questionnaires on asthma
      related quality of life (Mini Asthma Quality of Life Questionnaire) and asthma
      control (Asthma Control Questionnaire) were completed, and asthma events were
      noted. RESULTS: The Asthma Control Questionnaire score change over 1 year
      improved significantly more in the FENO-guided group (-0.17 [interquartile range
      {IQR}, -0.67 to 0.17] vs 0 [-0.33 to 0.50]; P = .045), whereas the Mini Asthma
      Quality of Life Questionnaire score did not (0.23 [IQR, 0.07-0.73] vs 0.07 [IQR, 
      0.20 to 0.80]; P = .197). The change in Asthma Control Questionnaire was
      clinically important in subpopulations with poor control at baseline (P = .03).
      Furthermore, the exacerbation rate (exacerbations/patient/y) was reduced by
      almost 50% in the FENO-guided group (0.22 [CI, 0.14-0.34] vs 0.41 [CI, 0.29
      0.58]; P = .024). Mean overall inhaled corticosteroid use was similar in both
      groups (P = .95). CONCLUSION: Use of FENO to guide anti-inflammatory treatment
      within primary care significantly reduced the exacerbation rate and improved
      asthma symptom control without increasing overall inhaled corticosteroid use.

PMID- 24565713
TI  - Effects of mometasone, fluticasone, and montelukast on bone mineral density in
      adults with asthma.
AB  - BACKGROUND: Associations of inhaled corticosteroids (ICS) with bone mineral
      density (BMD) loss have not been characterized consistently. OBJECTIVE: This
      randomized, double-blind study assessed effects of mometasone furoate (MF)
      administered via dry powder inhaler on BMD of patients with persistent asthma.
      METHODS: Adults with mild-moderate persistent asthma who did not receive ICS for
      >=3 months were randomized to MF 400 MUg once daily (QD) in the evening (pm), MF
      200 MUg QD pm, montelukast sodium (ML) 10 mg QD pm, or fluticasone propionate
      (FP) 250 MUg twice daily. Included patients had 25-hydroxy vitamin D levels >=15
      ng/mL at baseline. All the patients received calcium and vitamin D supplements
      for daily use during the trial. Duplicate BMD scans were done at baseline, 6
      months, and 1 year. The mean percentage change in lumbar spine (LS) BMD from
      baseline to end point for MF 400 MUg versus ML 10 mg was the primary analysis.
      Changes from baseline in left total femur BMD and femoral neck BMD were secondary
      assessments. RESULTS: At the end point, mean LS BMD increased 0.9% (MF 400 MUg),
      1.2% (ML), 0.7% (MF 200 MUg), and 1.1% (FP), with no significant differences for
      MF 400 MUg versus ML (-0.3% [95% CI, -1.01 to 0.27]) for LS BMD. No significant
      differences among treatments occurred for changes in left total femur BMD; all
      were slight increases. Changes in femoral neck BMD were 0.4% (MF 400 MUg), -0.2%
      (ML), -0.2% (MF 200 MUg), and -0.4% (FP); only the difference between MF 400 MUg
      and FP was statistically significant (P = .044). CONCLUSION: No detrimental
      effects on lumbar BMD were observed after up to 1 year of treatment with MF in
      comparison with ML for patients who received calcium and vitamin D supplements.

PMID- 24565714
TI  - IgE and IgG binding patterns and T-cell recognition of Fel d 1 and non-Fel d 1
      cat allergens.
AB  - BACKGROUND: Cat allergy affects approximately 15% of the population and is a
      major risk factor for asthma. The relative importance of cat allergens other than
      Fel d 1 is not known. OBJECTIVE: To compare IgE and IgG antibody binding and T
      cell recognition of the major cat allergen Fel d 1 with other cat proteins with
      known IgE binding properties. METHODS: IgE, IgG1, and IgG4 antibody to Fel d 1,
      2, 3, 4, 7, 8, and the undesignated IgE binding proteins haptoglobin and S100A12
      were measured in the plasma of 96 individuals with cat allergy and 78 individuals
      without cat allergy. Cytokines were measured from T cells stimulated with the cat
      allergens. RESULTS: An allergen other than Fel d 1 had the highest IgE binding
      specificity for 35% of individuals with cat allergy, and it bound more than 50%
      of their IgE antibody in 70% of these sera. Fel d 4, 7, and 8 were identified as
      the main contributors to the non-Fel d 1 IgE binding response and elicited
      inflammatory Th2 cytokines to a similar degree as Fel d 1. As expected, the
      average percentage of IgE binding to Fel d 1 for individuals was 55%. IgG4
      binding to Fel d 1 was detected in both subjects with allergy (30%) and subjects
      without allergy (19%). IgG4 binding to the other allergens was less prevalent but
      was found for both groups. IgG1 antibody was not detected to any of the newly
      described cat proteins. CONCLUSION: Fel d 4, 7, and 8 are allergens that should
      be included in the diagnosis and investigation of cat allergy.

PMID- 24565716
TI  - The safety or risk of antihistamine use in pregnancy: reassuring data are helpful
      but not sufficient.

PMID- 24565715
TI  - Assessment of antihistamine use in early pregnancy and birth defects.
AB  - BACKGROUND: Several studies have reported an association between use of specific
      antihistamines in early pregnancy and certain specific birth defects. OBJECTIVE:
      To test 16 previously hypothesized associations between specific antihistamines
      and specific birth defects, and to identify possible new associations. METHODS:
      We used 1998-2010 data from the Slone Epidemiology Center Birth Defects Study, a
      multicenter case-control surveillance program of birth defects in North America.
      Mothers were interviewed within 6 months of delivery about demographic,
      reproductive, medical, and behavioral factors, and details on the use of
      prescription and nonprescription medications. We compared first trimester
      exposure to specific antihistamines between 13,213 infants with specific
      malformations and 6982 nonmalformed controls by using conditional logistic
      regression to estimate odds ratios and 95% confidence intervals (CIs), with
      adjustment for potential confounders, including indication for use. RESULTS:
      Overall, 13.7% of controls were exposed to antihistamines during the first
      trimester. The most commonly used medications were diphenhydramine (4.2%),
      loratadine (3.1%), doxylamine (1.9%), and chlorpheniramine (1.7%). When estimates
      were stable, none supported the previously hypothesized associations. Among more
      than 100 exploratory comparisons of other specific antihistamine-defect pairs, 14
      had odds ratios >=1.5, of which 6 had 95% CI bounds excluding 1.0 before but not
      after adjustment for multiple comparisons. CONCLUSION: Our findings do not
      provide meaningful support for previously posited associations between
      antihistamines and major congenital anomalies; at the same time, we identified
      associations that had not been previously suggested. We suspect that previous
      associations may be chance findings in the context of multiple comparisons, a
      situation that may also apply to our new findings.

PMID- 24565717
TI  - A 58-year-old man with respiratory insufficiency after a 50-year history of
      hypersensitivity pneumonitis and pulmonary Aspergillus infections.

PMID- 24565718
TI  - Prescribing trends of epinephrine autoinjectors within an urban population.

PMID- 24565719
TI  - Respiratory symptoms in children with Ehlers-Danlos syndrome.

PMID- 24565720
TI  - Omalizumab mitigates anaphylaxis during ultrarush honey bee venom immunotherapy
      in monoclonal mast cell activation syndrome.

PMID- 24565721
TI  - Atopy and the development of chronic rhinosinusitis in children with allergic
      rhinitis.

PMID- 24565722
TI  - Anatomic and anthropometric determinants of intramuscular versus subcutaneous
      administration in children with epinephrine autoinjectors.

PMID- 24565723
TI  - The use of a tapering dose of methylprednisolone for asthma exacerbations: is it
      adequate?

PMID- 24565724
TI  - Anaphylaxis to peanuts in a 16-year-old girl with birch pollen allergy and with
      monosensitization to Ara h 8.

PMID- 24565725
TI  - Pneumococcal meningitis in a patient with IL-1 receptor-associated kinase-4
      deficiency: a case of failed prophylaxis.

PMID- 24565726
TI  - Administration of intravenous immunoglobulin to a patient with
      hypogammaglobulinemia and anti-IgA antibodies.

PMID- 24565727
TI  - Intramuscular versus intravenous immunoglobulin replacement therapy and
      measurement of immunoglobulin levels during immunoglobulin replacement therapy.

PMID- 24565728
TI  - An alternative approach to the chronic refractory cough?

PMID- 24565729
TI  - On the question of the association between immediate hypersensitivity to
      quinolones and neuromuscular blocking drug sensitization.

PMID- 24565730
TI  - Reply: To PMID 24565485.

PMID- 24565733
TI  - Event-related potential responses to perceptual reversals are modulated by
      working memory load.
AB  - While viewing ambiguous figures, such as the Necker cube, the available
      perceptual interpretations alternate with one another. The role of higher level
      mechanisms in such reversals remains unclear. We tested whether perceptual
      reversals of discontinuously presented Necker cube pairs depend on working memory
      resources by manipulating cognitive load while recording event-related potentials
      (ERPs). The ERPs showed early enhancements of negativity, which were obtained in
      response to the first cube approximately 500 ms before perceived reversals. We
      found that working memory load influenced reversal-related brain responses in
      response to the second cube over occipital areas at the 150-300 ms post-stimulus
      and over central areas at P3 time window (300-500 ms), suggesting that it
      modulates intermediate visual processes. Interestingly, reversal rates remained
      unchanged by the working memory load. We propose that perceptual reversals in
      discontinuous presentation of ambiguous stimuli are governed by an early (well
      preceding pending reversals) mechanism, while the effects of load on the reversal
      related ERPs may reflect general top-down influences on visual processing,
      possibly mediated by the prefrontal cortex.

PMID- 24565735
TI  - Postplacental intrauterine device insertion at a teaching hospital.
AB  - OBJECTIVE: To determine whether postplacental intrauterine device (IUD) insertion
      can be safely and effectively performed within a teaching program. STUDY DESIGN:
      This was a prospective cohort of 177 subjects planning vaginal delivery enrolled
      antenatally who desired postplacental IUD insertion of either the copper T380A
      IUD or levonorgestrel IUS. Insertions were performed primarily by resident
      physicians following a training session. Follow-up included a 4- to 8-week visit
      and telephone calls at 3 and 6 months. RESULTS: Ninety-nine subjects underwent
      successful postplacental IUD insertion of 100 attempts. Seventeen expulsions
      (17%) were noted: 10 complete and 7 partial. The study identified no differences
      in outcome by training level; however, the study lacked statistical power to
      evaluate anything other than large differences. CONCLUSION: Postplacental IUD
      insertions can be safely and effectively performed within a training program.
      IMPLICATIONS: A training protocol may safely and feasibly be initiated among
      physicians, advanced practice clinicians or trainees with no prior experience
      with postplacental IUD insertion. By initiating this practice, access to highly
      effective contraception may increase for patients who have difficulty returning
      for a visit or otherwise receiving effective methods.

PMID- 24565734
TI  - Impaired perception of mnemonic oldness, but not mnemonic newness, after parietal
      lobe damage.
AB  - In studies of episodic memory retrieval, recognition paradigms are known to
      elicit robust activations in the inferior parietal lobe. However, damage to this
      region does not produce severe deficits in episodic memory performance as indexed
      by typical accuracy measures. Rather, because problems with memory confidence are
      frequently reported, the observed deficits may be best described as "metamemory"
      or subjective memory deficits. Here, we further investigated the inferior
      parietal lobe's role in recognition memory as well as metamemory. We tested the
      hypothesis that the inferior parietal lobe gauges the perceived oldness of items,
      given several neuroimaging findings suggesting that a portion of the left
      inferior parietal lobe is sensitive to perceived oldness. We tested two patients
      with bilateral parietal lobe lesions and matched controls on an old/new
      recognition task. From these data we constructed receiver operating
      characteristic (ROC) curves by fitting the data with the unequal-variance signal
      detection (UVSD) model. The results revealed no memory impairment in terms of
      patients' accuracy. However, patients exhibited lower hit rates and false alarms
      rates at high confidence levels. Further, patients and controls differed in how
      they set decision criteria for making recognition responses. Patients' decision
      criteria for "old" responses were shifted in a conservative fashion such that
      they were unwilling to endorse recognized target items with high levels of
      confidence. These findings provide constraints on models of inferior parietal
      lobe contributions to episodic memory retrieval.

PMID- 24565736
TI  - ACIDFORM: a review of the evidence.
AB  - OBJECTIVE: ACIDFORM is a candidate microbicide with spermicidal properties. A
      large Phase 3 trial is underway, and it is anticipated that this product will be
      approved for contraceptive use and marketed soon in the United States. The goal
      of this article is to critically review the evidence supporting the properties,
      safety profile and different uses of ACIDFORM gel. STUDY DESIGN: We searched
      PubMed and Medline for any published literature on ACIDFORM. RESULTS: ACIDFORM is
      an acidifying agent that works by lowering the vaginal pH to enhance the normal
      vaginal defenses. In addition to strong acid-buffering properties, ACIDFORM has
      high bioadhesive and viscosity-retaining properties. Several Phase 1 clinical
      trials have demonstrated the vaginal safety of ACIDFORM used alone or in
      combination with a diaphragm, although dose-dependent side effects appear to be
      present. Studies investigating the efficacy of ACIDFORM against sexually
      transmitted infections (STIs) are promising, but further trials are needed.
      CONCLUSIONS: The properties of ACIDFORM offer many advantages for use, either
      alone or in combination with another active ingredient, such as Tenofovir.
      Potential applications for ACIDFORM include use as a personal lubricant, a
      vaginal contraceptive (alone or with a barrier method) and a microbicidal product
      or as a formulation vehicle for an active ingredient. IMPLICATIONS: ACIDFORM is a
      candidate female-controlled vaginal preparation with microbicidal and spermicidal
      properties. A dual protection method could prevent unwanted pregnancies and
      reduce the risk of STI acquisition.

PMID- 24565737
TI  - Operational assessments of Sayana(r) Press provision in Senegal and Uganda.
AB  - OBJECTIVE: Sayana(r) Press (SP) is a unique injectable contraceptive (depot
      medroxyprogesterone acetate, or DMPA) administered subcutaneously in the
      Uniject(TM) injection system.(1) SP simplifies the injection process; it requires
      no assembly of components and is easily disposable. This new technology appears
      to be well suited for community-based delivery of injectable contraception. The
      study objective was to evaluate SP management and administration in low-resource
      settings, focusing on how the delivery logistics, administration time, storage
      and waste-management requirements compare to the traditional intramuscular DMPA
      injectable (DMPA IM). STUDY DESIGN: We conducted 58 semistructured interviews
      with clinic providers and community health workers in Senegal and Uganda to
      identify the merits, challenges and appeal of SP relative to DMPA IM. RESULTS:
      Providers identified logistical challenges with the management and administration
      of DMPA IM, including stock outs, transportation, storage constraints, and, in a
      few instances, waste disposal. Most providers (between 63% and 88%, depending on
      the logistics issue) do not expect SP to either aggravate or solve those
      problems. Some envisioned that SP could facilitate supply management (5%),
      storage (11%) and waste disposal (22%). The all-in-one packaging of SP was
      perceived to reduce the incidence of mismatched supplies (syringes and vials),
      and its smaller size was expected to ease space constraints and reduce the
      frequency of safety box incineration. CONCLUSION: Adding SP to the method mix is
      unlikely to have a profound impact on clinic operations but may lessen logistical
      problems related to supply, storage and waste management. IMPLICATIONS: Community
      health workers and clinic providers who administer SP may see some modest
      improvements in service delivery logistics. Particularly in settings where
      service delivery logistical challenges are more pronounced, offering SP may
      facilitate injectable contraceptive delivery.

PMID- 24565738
TI  - Use of drug-susceptibility testing for management of drug-resistant tuberculosis,
      Thailand, 2004-2008.
AB  - In 2004, routine use of culture and drug-susceptibility testing (DST) was
      implemented for persons in 5 Thailand provinces with a diagnosis of tuberculosis
      (TB). To determine if DST results were being used to guide treatment, we
      conducted a retrospective chart review for patients with rifampin-resistant or
      multidrug-resistant (MDR) TB during 2004-2008. A total of 208 patients were
      identified. Median time from clinical sample collection to physician review of
      DST results was 114 days. Only 5.8% of patients with MDR TB were empirically
      prescribed an appropriate regimen; an additional 31.3% received an appropriate
      regimen after DST results were reviewed. Most patients with rifampin -resistant
      or MDR TB had successful treatment outcomes. Patients with HIV co-infection and
      patients who were unmarried or had received category II treatment before DST
      results were reviewed had less successful outcomes. Overall, review of available
      DST results was delayed, and results were rarely used to improve treatment. 

PMID- 24565739
TI  - Kyrgyzstan - a virtual narco-state?
AB  - Numerous myths have surrounded the drug trade in Central Asia over the past two
      decades. Analysts writing on the issue and the law enforcement structures of the
      respective countries often have no complete and accurate information about the
      scale of the trade, the different groups involved and the role of drugs-related
      money in politics. Generally there are two dominating views: the first considers
      Kyrgyzstan to be a virtual narco-state and overstates the involvement of
      politicians and police officials; the alternative underestimates the role of
      state representatives, describes the smuggling as more decentralised and chaotic
      and emphasises the role of organised crime gangs and radical Islamic
      organisations. Based on the interviews in the field conducted in January-March
      2012, this paper analyses these alternative perspectives and the empirical
      evidence supporting these views. It highlights methodological problems relating
      to research on similar issues, elucidates networks of smuggling and their links
      with politics and reflects on complexities in addressing these challenges. 

PMID- 24565740
TI  - Re: Chen et al.: Publication times, impact factors, and advance online
      publication in ophthalmology journals (Ophthalmology 2013;120:1697-701).

PMID- 24565741
TI  - Re: Ramakrishnaiah et al.: Reliability of magnetic resonance imaging for the
      detection of hypopituitarism in children with optic nerve hypoplasia
      (Ophthalmology 2014;121:387-91).

PMID- 24565742
TI  - Microstructure of beta-zone parapapillary atrophy and rate of retinal nerve fiber
      layer thinning in primary open-angle glaucoma.
AB  - OBJECTIVE: To investigate whether the rate of retinal nerve fiber layer (RNFL)
      thinning differs according to the microstructure of beta-zone parapapillary
      atrophy (PPA) as evaluated by spectral-domain (SD) optical coherence tomography
      (OCT) in primary open-angle glaucoma (POAG). DESIGN: Prospective, observational,
      comparative study. PARTICIPANTS: A total of 195 eyes with POAG that had been
      evaluated by serial SD-OCT RNFL thickness measurements for >= 2 years. METHODS:
      On the basis of the extent of Bruch's membrane (BM) within the beta-zone PPA
      (area without retinal pigment epithelium [RPE]), as shown in the infrared fundus
      images, PPA was divided into PPA+BM (PPA with intact BM) and PPA-BM (PPA devoid
      of BM). Eyes were categorized into group A (having PPA+BM only, n=64), group B
      (having both PPA+BM and PPA-BM, n=58), group C (having PPA-BM only, n=32), and
      group D (without beta-zone PPA, n=41). The rate of progressive OCT RNFL thinning
      was determined by linear regression and compared between groups. Factors
      influencing the rate of RNFL thinning were evaluated, including age, sex, follow
      up duration, history of filtering surgery, baseline RNFL thickness, baseline
      intraocular pressure (IOP), mean IOP and IOP fluctuation during follow-up, PPA
      types, baseline PPA width, PPA width increase, axial length (AXL), central
      corneal thickness, and visual field mean deviation (MD). MAIN OUTCOME MEASURES:
      Rate of thinning of OCT RNFL thicknesses over time. RESULTS: Patients in groups B
      and C were significantly younger and more myopic, and had a greater AXL, than
      those in groups A and D (all P<0.001). The rate of global RNFL thinning was
      significantly faster in group A (-1.66 +/- 2.94 MUm/year) than in the other
      groups (group B, -0.87 +/- 1.28 MUm/year; group C, 0.20 +/- 1.86 MUm/year; group
      D, -0.28 +/- 1.74 MUm/year; P = 0.001). Multivariate regression showed a
      significant association of shorter follow-up period (P = 0.016), greater baseline
      global RNFL thickness (P = 0.035), type of beta-zone PPA (group A, P = 0.023),
      and greater baseline PPA+BM width (P = 0.034) with a faster rate of RNFL
      thinning. CONCLUSIONS: The rate of RNFL thinning differed according to the
      microstructure of beta-zone PPA. It was faster for eyes with beta-zone PPA with
      intact BM than for eyes without beta-zone PPA or with beta-zone PPA devoid of BM.

PMID- 24565743
TI  - Author reply: To PMID 23972277.

PMID- 24565744
TI  - Vision loss and hearing loss in painting and musical composition.
AB  - This article considers the impact of vision and hearing loss on great painters
      and musical composers. The visual work of Mary Cassatt, Georgia O'Keeffe, Edgar
      Degas, and Claude Monet all showed alterations as their vision failed. In
      contrast, Gabriel Faure, Bedrich Smetana, and Ludwig von Beethoven wrote many of
      their best compositions while totally deaf, and Georg Friedrich Handel and
      Frederick Delius struggled to compose late in life when they lost their vision
      (although their hearing remained excellent). There are 2 major distinctions
      between the role of vision and hearing for these artistic disciplines. First,
      there is a surrogate means of "hearing" music, through the musical score, which
      allows composers to write and edit music while totally deaf. The greatest problem
      with deafness for a skilled composer is interference from internal noise
      (tinnitus). There is no surrogate for vision to allow a painter to work when the
      subject is a blur or the colors on the canvas cannot be distinguished. Second,
      although the appreciation of art is visual and that of music is auditory, the
      transcription of both art and musical composition is visual. Thus, visual loss
      does pose a problem for a composer accustomed to working with good sight, because
      it disrupts habitual methods of writing and editing music. 

PMID- 24565745
TI  - Health care utilization and barriers experienced by individuals with spinal cord
      injury.
AB  - OBJECTIVES: To identify from whom individuals with spinal cord injury (SCI) seek
      health care, the percentage who receive preventative care screenings, and the
      frequency and types of barriers they encounter when accessing primary and
      specialty care services; and to examine how sociodemographic factors affect
      access to care and receipt of preventative screenings. DESIGN: Cross-sectional,
      observational study using an Internet-based survey. SETTING: Internet based.
      PARTICIPANTS: Adults (N=108) with SCI who use a wheelchair as their primary means
      of mobility in the community. INTERVENTIONS: Not applicable. MAIN OUTCOME
      MEASURES: Health care utilization during the past year, barriers encountered when
      accessing health care facilities, and receipt of routine care and preventative
      screenings. RESULTS: All but 1 participant had visited a primary care provider
      within the past 12 months, and 85% had had >= 1 visit to specialty care
      providers. Accessibility barriers were encountered during both primary care
      (91.1%) and specialty care (80.2%) visits; most barriers were clustered in the
      examination room. The most prevalent barriers were inaccessible examination
      tables (primary care=76.9%; specialty care=51.4%) and lack of transfer aids
      (primary care=69.4%; specialty care=60.8%). Most participants had not been
      weighed during their visit (89%) and had remained seated in their wheelchair
      during their examinations (85.2%). Over one third of individuals aged >= 50 years
      had not received a screening colonoscopy, 60% of women aged >= 50 years had not
      had a mammogram within the past year, 39.58% of women had not received a
      Papanicolaou smear within the previous 3 years, and only 45.37% of respondents
      had ever received bone density testing. CONCLUSIONS: Individuals with SCI face
      remediable obstacles to care and receive fewer preventative care screenings than
      their nondisabled counterparts. We recommend that clinics conduct Americans with
      Disabilities Act self-assessments, ensure that their clinical staff are properly
      trained in assisting individuals with mobility disabilities, and take a proactive
      approach in discussing preventative care screenings with their patients who have
      SCI.

PMID- 24565746
TI  - [Leuko-glycemic index as an in-hospital prognostic marker in patients with ST
      segment elevation myocardial infarction].
AB  - INTRODUCTION: Blood glucose and white blood cell count on admission have
      demonstrated prognostic significance in patients with myocardial infarction;
      leuko-glycemic index, a recently proposed marker, still lacks enough knowledge
      about its value. OBJECTIVES: To evaluate the leuko-glycemic index as a prognostic
      marker in patients with ST-segment elevation myocardial infarction. METHODS: A
      retrospective study was carried out in 128 patients with ST-segment elevation
      myocardial infarction, who were admitted between January 2009 and October 2010 in
      the Intensive Care Unit of the Hospital Dr. Celestino Hernandez Robau. Clinical
      and laboratory data were collected, including glucose and white blood cell count
      on admission, from which we calculated the leuko-glycemic index and we evaluated
      its prognostic value. RESULTS: Patients who had a poor outcome such as death,
      major cardiac complications and failed-thrombolysis, showed higher values of
      leuko-glycemic index (P<.01), which was correlated with several variables such as
      Killip class, and heart rate on admission (P=.000). We obtained a cutoff point of
      1.158, patients with higher values had 3 times higher probability of death and
      complications (odds ratio=3,0; IC 95%: 1,2-7,3; P=.005); so leuko-glycemic index
      was an independent predictor after multivariate analysis. CONCLUSIONS: The leuko
      glycemic index was associated with an increased occurrence of hospital
      complications, death and failed-thrombolysis; its pathological value was an
      independent predictor of in-hospital death and complications in the studied
      sample.

PMID- 24565747
TI  - The use of TALENs for nonhomologous end joining mutagenesis in silkworm and
      fruitfly.
AB  - Transcription activator-like effector nucleases (TALENs) are custom-made enzymes
      designed to cut double-stranded DNA at desired locations. The DNA breaks are
      repaired either by error-prone non-homologous end-joining (NHEJ) pathway or via
      homologous recombination requiring homologous DNA as a template for the repair.
      TALENs are used for site-specific mutagenesis in an extended range of organisms
      including insects. We will describe here a simple TALEN-based mutagenesis
      protocol suitable for the generation of germline mutations in Bombyx mori and
      Drosophila melanogaster. The protocol includes assembly of specific TAL modules,
      in vitro synthesis of TALEN RNAs, egg microinjection and mutation detection using
      PCR analysis. Our procedure allows a high frequency induction of NHEJ mutations,
      which often allows the reception of homozygous mutants already in the G1. 

PMID- 24565748
TI  - Effective identification of essential proteins based on priori knowledge, network
      topology and gene expressions.
AB  - Identification of essential proteins is very important for understanding the
      minimal requirements for cellular life and also necessary for a series of
      practical applications, such as drug design. With the advances in high throughput
      technologies, a large number of protein-protein interactions are available, which
      makes it possible to detect proteins' essentialities from the network level.
      Considering that most species already have a number of known essential proteins,
      we proposed a new priori knowledge-based scheme to discover new essential
      proteins from protein interaction networks. Based on the new scheme, two
      essential protein discovery algorithms, CPPK and CEPPK, were developed. CPPK
      predicts new essential proteins based on network topology and CEPPK detects new
      essential proteins by integrating network topology and gene expressions. The
      performances of CPPK and CEPPK were validated based on the protein interaction
      network of Saccharomyces cerevisiae. The experimental results showed that the
      priori knowledge of known essential proteins was effective for improving the
      predicted precision. The predicted precisions of CPPK and CEPPK clearly exceeded
      that of the other 10 previously proposed essential protein discovery methods:
      Degree Centrality (DC), Betweenness Centrality (BC), Closeness Centrality (CC),
      Subgraph Centrality (SC), Eigenvector Centrality (EC), Information Centrality
      (IC), Bottle Neck (BN), Density of Maximum Neighborhood Component (DMNC), Local
      Average Connectivity-based method (LAC), and Network Centrality (NC). Especially,
      CPPK achieved 40% improvement in precision over BC, CC, SC, EC, and BN, and CEPPK
      performed even better. CEPPK was also compared to four other methods (EPC, ORFL,
      PeC, and CoEWC) which were not node centralities and CEPPK was showed to achieve
      the best results. 

PMID- 24565749
TI  - Psychological and social outcome of epilepsy in well-functioning children and
      adolescents. A 10-year follow-up study.
AB  - BACKGROUND: From a population based study of epilepsy in Swedish children a
      subgroup designated well-functioning with an epilepsy diagnosis in 1997 was
      worked up from a medical point of view 10 years later. AIM: To describe the
      psychological and social outcome in this subgroup. METHODS: Thirty-one patients
      aged 11-22 years and their parents/partners responded to a questionnaire
      according to Achenbach System of Empirically Based Assessment (ASEBA) to evaluate
      behavioural and emotional problems, and social competence. RESULTS: Active
      epilepsy, diagnosed in 32%, was related to attention problems, somatic
      complaints, and school problems. Polytherapy, used in 16%, was related to
      attention problems and aggressive behaviour. School problems were found in six of
      seven children younger than 18 years. Internalizing, externalizing, and 'other'
      syndromes were found in 29% of the individuals, but a grouping of these syndromes
      in the clinical range only in two (6.5%), a girl with generalized tonic-clonic
      seizures alone, and a boy with structural focal epilepsy. Both had active
      epilepsy and were treated with polytherapy. All ten individuals with Rolandic
      epilepsy were classified as normal. The answers to the ASEBA questionnaire of
      individuals and parents/partners were inconsistent, and parents generally stated
      more problems than the individuals. SUMMARY: This 10-year follow-up study of
      psychological and social outcome in well-functioning children and adolescents
      with childhood onset epilepsy shows some emotional, behavioural, and social
      problems. Thus, early information to increase knowledge about epilepsy and
      associated psychological co-morbidities in order to decrease risk of low self
      esteem, social anxiety, and depression later in life is of importance.

PMID- 24565750
TI  - Delayed-enhancement magnetic resonance imaging at 3.0T using 0.15mmol/kg of
      contrast agent for the assessment of chronic myocardial infarction.
AB  - OBJECTIVE: A recent international, multicenter, double-blinded, randomized trial
      shows delayed-enhanced magnetic resonance imaging (DE-MRI) using contrast doses
      of >=0.2mmol/kg is effective in the detection and assessment of myocardial
      infarction (MI), and 0.1mmol/kg is not enough; intermediate doses between 0.1 and
      0.2mmol/kg have not been tested. The aim of this study was to prospectively test
      the performance of DE-MRI using 0.15mmol/kg of contrast agent for the detection
      of MI. MATERIALS AND METHODS: A total of 31 consecutive patients with chronic MI
      underwent DE-MRI at 3.0T using both 0.15mmol/kg and 0.2mmol/kg of contrast agent
      in random order and on separate days. Infarction segment and infarction size were
      compared on DE-MRI images using a 17-segment model. Bland-Altman analysis was
      used to analyze correlation and agreement between global infarct sizes. RESULTS:
      DE-MRI showed enhanced myocardium in all the 31 patients with chronic MI. There
      was no significant difference between the 0.15mmol/kg and 0.2mmol/kg images in
      all 31 patients based on the infarction segment (7.87+/-2.72 vs. 7.81+/-2.64,
      respectively; p=0.33). There was no significant difference between the infarction
      size obtained from 0.15mmol/kg acquisition and that from 0.2mmol/kg acquisition
      (16.3+/-7.8% vs. 16.4+/-7.9%, respectively; p=0.87). A strong correlation between
      the infarction size obtained from 0.15mmol/kg acquisition and that from
      0.2mmol/kg acquisition was indicated through Bland-Altman analysis. CONCLUSION:
      DE-MRI at 3.0T using 0.15mmol/kg of contrast agent is effective for the
      assessment of MI.

PMID- 24565751
TI  - Symptomatic atypical femoral fractures are related to underlying hip geometry.
AB  - The benefits of bisphosphonates are well documented, but prolonged use has been
      associated with atypical femur fractures. Radiographic markers for fracture
      predisposition could potentially aid in safer medication use. In this case
      control designed study, we compared hip radiographic parameters and the
      demographic characteristics of chronic bisphosphonate users who sustained an
      atypical femoral fracture with a group of chronic bisphosphonate users who did
      not sustain an atypical femur fracture and also a group who sustained an
      intertrochanteric hip fracture. Radiographic parameters included were neck-shaft
      angle (NSA), hip-axis length (HAL) and center-edge angle (CE). Multivariate
      regression was used to evaluate the relationship between radiographic measures
      and femur fracture. Receiver-operating characteristic analysis determined cut-off
      points for neck-shaft angle and risk of atypical femur fracture. Ultimately, pre
      fracture radiographs of 53 bisphosphonate users who developed atypical fracture
      were compared with 43 asymptomatic chronic bisphosphonate users and 64
      intertrochanteric fracture patients. Duration of bisphosphonate use did not
      statistically differ between users sustaining atypical fracture and those without
      fracture (7.9 [+/-3.5] vs. 7.7 [+/-3.3] years, p=0.7). Bisphosphonate users who
      fractured had acute/varus pre-fracture neck-shaft angles (p<0.001), shorter hip
      axis length (p<0.01), and narrower center-edge angles (p<0.01). Regression
      analysis revealed associations between neck-shaft angle (OR=0.89 [95% CI=0.81
      0.97; p=0.01), center edge angle (OR=0.89 [95% CI=0.80-0.99]; p=0.03), and BMI
      (OR=1.15 [95% CI=1.02-1.31; p=0.03) with fracture development. ROC curve analysis
      (AUC=0.67 [95% CI=0.56-0.79]) determined that a cut-off point for neck-shaft
      angle <128.3 degrees  yielded 69% sensitivity and 63% specificity for development
      of atypical femoral fracture. Ultimately, an acute/varus angle of the femoral
      neck, high BMI, and narrow center-edge angle were associated with development of
      atypical femur fracture in long-term bisphosphonate users. Patients on long-term
      bisphosphonates should be regularly radiographically evaluated in order to assess
      for potential risk of atypical fracture. 

PMID- 24565752
TI  - First assessment of classical swine fever marker vaccine candidate CP7_E2alf for
      oral immunization of wild boar under field conditions.
AB  - Oral vaccination against classical swine fever (CSF) is a potent tool to control
      disease outbreaks in wild boar. So far, vaccination campaigns have been carried
      out using live attenuated vaccines that do not allow serological differentiation
      of infected from vaccinated animals (DIVA). Although this drawback is acceptable
      for wild boar, the use of marker vaccines would facilitate studies on disease and
      vaccination dynamics. Recently, the CSF marker vaccine candidate CP7_E2alf was
      assessed for oral immunization under laboratory conditions. Promising results
      prompted efforts to study the vaccine candidate under field conditions and in
      bait formulation. In this context, two oral vaccination campaigns were carried
      out with CP7_E2alf bait vaccines in two areas called 'faunistic-hunting farms' in
      the region of Umbria, Italy. One campaign was conducted using single vaccination,
      the second with the routinely employed double vaccination strategy. Both
      campaigns were carried out before concerted hunting actions were performed. Bait
      uptake, vaccine virus detection and antibody responses were assessed along with
      inspections upon gutting. As a comparator, seven wild boar were hand-fed with
      baits under laboratory conditions. In the field, bait uptake ranged from 63.7% to
      98.7%, whereas antibody prevalence reached only 33.3-35.1%. The marker serology
      showed a strong influence of sample quality on the test outcome with a total of
      85% of samples being classified correctly. Vaccine virus was not detectable.
      Under hand feeding conditions, six out of seven wild boar took up at least one
      bait, and five of them showed detectable antibody levels seven weeks after
      vaccination. These results were supplemented by stability tests. Appropriate
      stability of vaccine virus was shown both under field and laboratory conditions.
      In total, most results were in line with our expectations. However, optimization
      of the DIVA assay has to be attempted in the future. 

PMID- 24565753
TI  - Attenuated strains of Mycobacterium avium subspecies paratuberculosis as vaccine
      candidates against Johne's disease.
AB  - Mycobacterium avium subspecies paratuberculosis (M. paratuberculosis) is the
      causative agent of Johne's disease in ruminants. Johne's disease has a severe
      economic impact on the dairy industry in the USA and worldwide. In an effort to
      combat this disease, we screened several transposon mutants that were attenuated
      in the murine model of paratuberculosis for the potential use as live attenuated
      vaccines. Using the murine model, two vaccine candidates (pgs1360, pgs3965 with
      mutations of fabG2_2 and umaA1, respectively) were at or below the limit of
      detection for tissue colonization suggesting their low level persistence and
      hence safety. Prior to challenge, both candidates induced a M. paratuberculosis
      specific IFN-gamma, an indication of eliciting cell-mediated immunity. Following
      challenge with a virulent strain of M. paratuberculosis, the two vaccine
      candidates significantly reduced bacterial colonization in organs with reduced
      histological scores compared to control animals. In addition, one of the vaccine
      candidates (pgs3965) also induced IL-17a, a cytokine associated with protective
      immunity in mycobacterial infection. Our analysis suggested that the pgs3965
      vaccine candidate is a potential live-attenuated vaccine that could be tested
      further in ruminant models of paratuberculosis. The analysis also validated our
      screening strategy to identify effective vaccine candidates against intracellular
      pathogens. 

PMID- 24565754
TI  - Generation and molecular characterization of a monoclonal antibody reactive with
      conserved epitope in sphingomyelinases D from Loxosceles spider venoms.
AB  - We report the production of a neutralizing monoclonal antibody able to recognize
      the venoms of three major medically important species of Loxosceles spiders in
      Brazil. The mAb was produced by immunization of mice with a toxic recombinant L.
      intermedia sphingomyelinase D {SMases D isoform (rLiD1)} [1] and screened by
      enzyme-linked immunosorbent assay (ELISA) using L. intermedia, L. laeta and L.
      gaucho venoms as antigens. One clone (LiD1mAb16) out of seventeen anti-rLiD1
      hybridomas was cross-reactive with the three whole Loxosceles venoms. 2D Western
      blot analysis indicated that LiD1mAb16 was capable of interacting with 34
      proteins of 29-36kDa in L. intermedia, 33 in L. gaucho and 27 in L. laeta venoms.
      The results of immunoassays with cellulose-bound peptides revealed that the
      LiD1mAb16 recognizes a highly conserved linear epitope localized in the catalytic
      region of SMases D toxins. The selected mAb displayed in vivo protective activity
      in rabbits after challenge with rLiD1. These results show the potential
      usefulness of monoclonal antibodies for future therapeutic approaches and also
      opens up the perspective of utilization of these antibodies for immunodiagnostic
      assays in loxoscelism. 

PMID- 24565755
TI  - Can the success of pneumococcal conjugate vaccines for the prevention of
      pneumococcal diseases in children be extrapolated to adults?
AB  - Before conjugate pneumococcal vaccines (PCVs) were introduced it was estimated
      that Streptococcus pneumoniae caused 500,000 cases of pneumonia, 50,000 cases of
      bacteremia and 3000 cases of meningitis annually in the United States in both
      children and adults. After 10 years of routine use of the 7-valent pneumococcal
      conjugate vaccine (PCV7) the incidence of vaccine-type pneumococcal diseases
      (PDs) had significantly decreased in vaccinated children (direct effect) and
      unvaccinated subjects of all ages (indirect effect). Second generation, higher
      valent PCVs, especially 13-valent (PCV13), routinely implemented since 2010, have
      reduced the incidence of PDs caused by the six additional non-PCV7 serotypes, in
      both vaccinated and unvaccinated subjects. The licence for this vaccine has
      recently been extended to include adults aged 18 to 49 in Europe. Although PCV13
      has an indirect effect on IPD in adults, this will probably not achieve the same
      level of disease control in adults and the elderly (especially those at high
      risk) as that obtained in vaccinated children. As highlighted in this paper,
      differences exist between children and adults for PD manifestations (incidence,
      morbidity and mortality) and serotypes isolated in nasopharyngeal carriage and
      diseases, so benefits from adult vaccination must be considered in this light.
      PCV13 induces an immune response in adults that is non-inferior for all serotypes
      common with the 23-valent plain polysaccharide vaccine that is currently
      recommended for adults and even superior for many serotypes. Although there is no
      evidence that this immune response translates to clinical efficacy in adults as
      seen in children, the results from a randomised trial in The Netherlands,
      expected in 2014, should provide the missing evidence. This evidence and
      efficient surveillance systems should provide the necessary data, essential for
      policy makers in their decisions on adult pneumococcal vaccination policies. 

PMID- 24565758
TI  - Acute phase endovascular intervention on a pseudoaneurysm formed due to rupture
      of an anterior communicating artery aneurysm.
AB  - A 79-year-old woman presented with a subarachnoid hemorrhage. Angiography
      revealed pseudoaneurysm formation due to rupture of a true saccular anterior
      communicating artery aneurysm. Coil embolization, limited to the true aneurysm,
      was performed successfully with a favorable clinical outcome. This procedure can
      be considered as an alternative treatment option for similar aneurysms in cases
      where surgical clipping is contraindicated. 

PMID- 24565756
TI  - Repression of glucocorticoid-stimulated angiopoietin-like 4 gene transcription by
      insulin.
AB  - Angiopoietin-like 4 (Angptl4) is a glucocorticoid receptor (GR) primary target
      gene in hepatocytes and adipocytes. It encodes a secreted protein that inhibits
      extracellular LPL and promotes adipocyte lipolysis. In Angptl4 null mice,
      glucocorticoid-induced adipocyte lipolysis and hepatic steatosis are compromised.
      Markedly, insulin suppressed glucocorticoid-induced Angptl4 transcription. To
      unravel the mechanism, we utilized small molecules to inhibit insulin signaling
      components and found that phosphatidylinositol 3-kinase and Akt were vital for
      the suppression in H4IIE cells. A forkhead box transcription factor response
      element (FRE) was found near the 15 bp Angptl4 glucocorticoid response element
      (GRE). Mutating the Angptl4 FRE significantly reduced glucocorticoid-induced
      reporter gene expression in cells. Moreover, chromatin immunoprecipitation
      revealed that GR and FoxO1 were recruited to Angptl4 GRE and FRE in a
      glucocorticoid-dependent manner, and cotreatment with insulin abolished both
      recruitments. Furthermore, in 24 h fasted mice, significant occupancy of GR and
      FoxO1 at the Angptl4 GRE and FRE was found in the liver. In contrast, both
      occupancies were diminished after 24 h refeeding. Finally, overexpression of
      dominant negative FoxO1 mutant abolished glucocorticoid-induced Angptl4
      expression, mimicking the insulin suppression. Overall, we demonstrate that both
      GR and FoxO1 are required for Angptl4 transcription activation, and that FoxO1
      negatively mediates the suppressive effect of insulin.

PMID- 24565759
TI  - Combined use of Solitaire FR and Penumbra devices for endovascular treatment of
      cerebral venous sinus thrombosis in a child.
AB  - A pre-teenager with newly diagnosed ulcerative colitis presented to an emergency
      department with acute headache, altered mental status and bilateral lower
      extremity weakness. Head CT demonstrated acute thrombus in the vein of Galen and
      straight sinus, and the patient was started on a heparin infusion. The patient
      clinically deteriorated and became unresponsive. In view of the rapid
      deterioration despite anticoagulation therapy, the patient was taken for
      endovascular treatment. A novel endovascular approach was performed with combined
      use of Solitaire FR and Penumbra devices to enhance access to the straight sinus
      and to limit intraprocedural blood loss. The post-treatment head CT demonstrated
      a decrease in hyperattenuation within the vein of Galen and straight sinus. The
      neurologic status improved within 24 h. The patient was discharged home with a
      normal neurologic examination.

PMID- 24565760
TI  - Mindfulness meditation: do-it-yourself medicalization of every moment.
AB  - This paper examines mindfulness as a popular and paradigmatic alternative healing
      practice within the context of contemporary medicalization trends. In recognition
      of the increasingly influential role popular media play in shaping ideas about
      illness and healing, what follows is a discursive analysis of bestselling
      mindfulness meditation self-help books and audio recordings by Jon Kabat-Zinn.
      The central and contradictory elements of this do-it-yourself healing practice as
      presented in these materials are best understood as aligned with medicalization
      trends for three principal reasons. First, mindfulness represents a significant
      expansion in the definition of disease beyond that advanced by mainstream
      medicine. Second, its etiological model intensifies the need for therapeutic
      surveillance and intervention. Third, by defining healing as a never-ending
      process, it permanently locates individuals within a disease-therapy cycle. In
      sum, the definition, cause, and treatment of disease as articulated by popular
      mindfulness resources expands the terrain of experiences and problems that are
      mediated by medical concepts. The case of mindfulness is a potent illustration of
      the changing character of medicalization itself. 

PMID- 24565757
TI  - BRCA1 is a novel regulator of metabolic function in skeletal muscle.
AB  - Breast cancer type 1 (BRCA1) susceptibility protein is expressed across multiple
      tissues including skeletal muscle. The overall objective of this investigation
      was to define a functional role for BRCA1 in skeletal muscle using a
      translational approach. For the first time in both mice and humans, we identified
      the presence of multiple isoforms of BRCA1 in skeletal muscle. In response to an
      acute bout of exercise, we found increases in the interaction between the native
      forms of BRCA1 and the phosphorylated form of acetyl-CoA carboxylase. Decreasing
      BRCA1 content using a shRNA approach in cultured primary human myotubes resulted
      in decreased oxygen consumption by the mitochondria and increased reactive oxygen
      species production. The decreased BRCA1 content also resulted in increased
      storage of intracellular lipid and reduced insulin signaling. These results
      indicate that BRCA1 plays a critical role in the regulation of metabolic function
      in skeletal muscle. Collectively, these data reveal BRCA1 as a novel target to
      consider in our understanding of metabolic function and risk for development of
      metabolic-based diseases. 

PMID- 24565761
TI  - Long-term consequences of female genital mutilation in a European context: self
      perceived health of FGM women compared to non-FGM women.
AB  - Female genital mutilation (FGM) concerns an estimated half a million women in
      Europe. The studies based in countries where migrant women have settled highlight
      the need for more accurate information on FGM health consequences, in a European
      health care context. Excision and Handicap (ExH) is a multi-centric survey based
      on case-control methodology and conducted in France to assess the long-term
      consequences of FGM, sampling both FGM and non-FGM adult women. The interviews
      were conducted in 74 mother-and-child health centres and hospital departments
      providing gynaecological and family planning services in five French regions. The
      two groups were compared on health indicators (self-perceived health, illnesses,
      symptoms) and functioning indicators (daily, sexual and reproductive life) for
      cases (n = 678) and controls (n = 1706). Multivariate logistic models highlighted
      FGM-related health problems. Among women living in France, FGM was significantly
      associated with poor health indicators: gynaecological and urinary infections (OR
      = 2.0), sleep disorders (OR = 1.4), intense pain (OR = 1.5), difficulties in
      daily life (OR = 1.5) and in sexual life (OR = 1.7) or tearing during childbirth
      (OR = 1.6). Our results suggest that, even in a favourable healthcare context,
      FGM exposes women to long-term health problems, including in areas neglected in
      previous research. They confirm the need to establish recommendations to help
      physicians understand these women's needs.

PMID- 24565762
TI  - Practical advances in drug hypersensitivity.

PMID- 24565763
TI  - Antibiotic allergies in children and adults: from clinical symptoms to skin
      testing diagnosis.
AB  - Hypersensitivity reactions to beta-lactam and non-beta-lactam antibiotics are
      commonly reported. They can be classified as immediate or nonimmediate according
      to the time interval between the last drug administration and their onset.
      Immediate reactions occur within 1 hour after the last drug administration and
      are manifested clinically by urticaria and/or angioedema, rhinitis, bronchospasm,
      and anaphylactic shock; they may be mediated by specific IgE-antibodies.
      Nonimmediate reactions occur more than 1 hour after the last drug administration.
      The most common manifestations are maculopapular exanthems; specific T
      lymphocytes may be involved in this type of manifestation. The diagnostic
      evaluation of hypersensitivity reactions to antibiotics is usually complex. The
      patient's history is fundamental; the allergic examination is based mainly on in
      vivo tests selected on the basis of the clinical features and the type of
      reaction, immediate or nonimmediate. Immediate reactions can be assessed by
      immediate-reading skin tests and, in selected cases, drug provocation tests.
      Nonimmediate reactions can be assessed by delayed-reading skin tests, patch
      tests, and drug provocation tests. However, skin tests have been well validated
      mainly for beta-lactams but less for other classes of antibiotics. 

PMID- 24565764
TI  - Indications, protocols, and outcomes of drug desensitizations for chemotherapy
      and monoclonal antibodies in adults and children.
AB  - Advances in the understanding of various malignancies and chronic inflammatory
      diseases has led to the development of better treatment options for prolonging
      patient survival and minimizing morbidity. The recognition of "first-line"
      chemotherapy and monoclonal agents for these conditions has given more urgency to
      the need to re-administer these drugs in cases of drug hypersensitivity
      reactions. Therefore, in these cases, not only is desensitization considered when
      there is no alternative therapy available but also when alternative treatments
      are considered therapeutically inferior and/or more toxic. In this article, we
      describe the steps involved in the evaluation of these patients, factors to
      consider before making a decision to desensitize, the implementation of
      desensitization protocols, and the outcomes of such procedures. 

PMID- 24565766
TI  - Accountable care organizations and the allergist: challenges and opportunities.
AB  - For decades, health care policy experts have wrestled with ways to solve problems
      of access, cost, and quality in US health care. The current consensus is that the
      solution to all three lies in changing financial incentives for providers and
      delivering care through integrated systems. The currently favored vehicle for
      this, both in the public and private sectors, is through Accountable Care
      Organizations (ACOs). Medicare has several models and has fostered rapid growth
      in the number of operative ACOs. At least an equal number of private ACOs are in
      operation. Whether or not these organizations will fulfill their promise is
      unknown but there is reason for cautious optimism. Allergists can and should be
      part of the process of this transformation in our health care system. They can be
      integral to helping these organizations save money by reducing hospitalizations
      and improving the quality of allergy and asthma care in the populations served.
      In order to accomplish this, allergists must become more involved in their
      medical communities and hospitals. 

PMID- 24565767
TI  - Oxaliplatin hypersensitivity: evaluation, implications of skin testing, and
      desensitization.
AB  - BACKGROUND: Oxaliplatin hypersensitivity (OXS) presents a challenge in the
      treatment of oxaliplatin-sensitive malignancies. OBJECTIVE: To analyze patient
      characteristics of patients with OXS, skin test results, and desensitization
      outcomes to optimize management. METHODS: Over 5 years, 48 patients with OXS were
      referred to the allergy/immunology unit at Massachusetts General Hospital. Their
      clinical reaction patterns were analyzed. Immediate hypersensitivity skin testing
      was used for risk stratification, and drug desensitizations were performed by
      using 3 related continuous intravenous protocols that were chosen based on
      clinical history, skin test reactivity, and the patients' previous
      desensitization outcomes. RESULTS: OXS occurred in both sexes, with mostly
      gastrointestinal-related tumors. Hypersensitivity reaction (HSR) onset had
      occurred during any course of therapy (course nos. 1-28), with a median onset at
      course no. 8. HSR to oxaliplatin was similar to those observed with cisplatin and
      carboplatin, including cutaneous, cardiovascular, pulmonary, and gastrointestinal
      symptoms. However, neurologic symptoms, including tingling, and systemic
      symptoms, including fever and chills, occurred more often in patients with OXS.
      Unique to OXS, 2 patients developed drug-induced thrombocytopenia; 1 patients
      also developed drug-induced hemolytic anemia. Skin testing was positive for the
      majority of patients with OXS (27/46 [59%]) and correlated with a greater
      likelihood of developing an HSR during subsequent desensitizations. We safely
      performed 200 desensitizations in 48 patients with OXS. CONCLUSION: OXS is common
      with much similarity to other platin agents but also have distinct differences in
      the onset of hypersensitivity, sex, tumor type, drug-induced hemolytic anemia,
      and drug-induced thrombocytopenia. Skin testing was helpful for risk
      stratification. All of the desensitizations were completed successfully.

PMID- 24565768
TI  - Retrospective study of drug-induced anaphylaxis treated in the emergency
      department or hospital: patient characteristics, management, and 1-year follow
      up.
AB  - BACKGROUND: Drugs are a common cause of anaphylaxis, which is potentially life
      threatening. OBJECTIVE: We sought to describe US patients with an emergency
      department (ED) visit or hospitalization for drug-induced anaphylaxis (DIA),
      including postdischarge follow-up care. METHODS: By using International
      Classification of Diseases, Ninth Revision codes in the MarketScan Database, we
      identified all patients with an ED visit and/or hospitalization for DIA between
      2002 and 2008 (index date = initial ED visit and/or hospitalization). Inclusion
      required continuous full insurance coverage >=1 year in the pre- and postindex
      period. We examined patient factors during the preindex period, characteristics
      of the index event, and outcomes during the postindex period. RESULTS: The cohort
      included 716 patients with an ED visit and/or hospitalization for DIA (mean age,
      48 years; 71% women). Most patients (71%) were managed in the ED, and only 8% of
      the patients with DIA treated in the ED received epinephrine. For those admitted,
      patients were hospitalized for a median of 3 days, and 41% spent time in the
      intensive care unit. Cardiorespiratory failure occurred in 5% of the patients in
      the ED and 23% of the patients who were hospitalized. The patients with a
      concomitant allergic condition were more likely to see an allergist/immunologist
      than those without a concomitant allergic condition, but 82% did not receive any
      subsequent care with an allergist/immunologist in the 1 year after the ED visit
      and/or hospitalization for DIA. CONCLUSION: Drugs are a common, yet under
      recognized, cause of anaphylaxis. Only a small number of patients with DIA
      received epinephrine in the ED or had subsequent care with an
      allergist/immunologist. These findings are novel and identify areas for
      improvement in the care of individuals with DIA.

PMID- 24565769
TI  - Successful outpatient graded administration of trimethoprim-sulfamethoxazole in
      patients without HIV and with a history of sulfonamide adverse drug reaction.
AB  - BACKGROUND: The outcomes of trimethoprim-sulfamethoxazole (TMP-SMX)
      desensitization have been widely reported in the HIV literature but less so in
      the non-HIV literature. OBJECTIVE: To evaluate the safety and efficacy of graded
      administration of TMP-SMX in patients without HIV and with a history of TMP-SMX
      adverse drug reaction (ADR). METHODS: A retrospective chart review, 2004-2012, of
      all the patients without HIV seen in the Division of Allergic Diseases and with a
      history of TMP-SMX ADR who underwent outpatient graded administration of TMP-SMX
      was conducted. The medical record was reviewed for age, sex, details of the
      initial ADR to TMP-SMX, an indication for TMP-SMX administration, and outcome.
      Patients also were contacted by telephone, and medical records were reviewed to
      determine long-term outcomes. RESULTS: Seventy-two patients (46 women [64%]; mean
      [SD] age, 57.7 +/- 13.89 years]) were included. The most common patient-reported
      reactions to TMP-SMX were rash 39 (54%), and hives 9 (13%). TMP-SMX
      administration was needed for the following indications: prophylaxis (62 [86%])
      and treatment of infection (10 [14%]). Forty-three of the patients (60%)
      underwent a 1-day TMP-SMX administration protocol. Thirty-five of the 43 (81%)
      underwent a 6-step (90 minutes to 6 hours) protocol and 7 of the 43 (16%)
      underwent a novel 14-step TMP-SMX protocol. Twenty-nine (40%) underwent a >1-day
      TMP-SMX administration protocol. Our overall success rate was 90% (mean duration
      of 11 months). Ninety-eight percent of the patients successfully completed a 1
      day graded administration protocol, and 76% successfully completed a >1-day
      protocol. TMP-SMX was stopped in 8 patients because of the ADR. CONCLUSION: We
      report the largest case series of successful outpatient graded administration of
      TMP-SMX with both 1-day and >1-day protocols, which have shown to be safe and
      well tolerated in patients without HIV and with a history of sulfonamide ADR.

PMID- 24565770
TI  - Change in asthma control over time: predictors and outcomes.
AB  - BACKGROUND: Maintenance of asthma control over time is a clear goal of national
      asthma guidelines, but few studies have addressed the natural history of asthma
      control over time. OBJECTIVE: To assess the impairment domain of asthma control
      over time in patients with persistent asthma and to determine predictors and
      consequences of controlled and uncontrolled asthma over time. METHODS: Patients
      18-56 years old with persistent asthma who completed baseline (November 2007) and
      follow-up asthma surveys (April, July, October 2008) were included in the study.
      The survey included the Asthma Control Test as well as questions regarding other
      patient and asthma characteristics. Health care utilization (pharmacy and
      exacerbations) for 2008 was obtained from administrative data. RESULTS: The
      baseline and first follow-up surveys were completed by 1267 patients, and all 4
      surveys were completed by 782 patients. Patients with well-controlled asthma at
      baseline were significantly more likely (P < .0001) to have well-controlled
      asthma over the following year (76.2%-80.4%) than patients with uncontrolled
      asthma at baseline (33.5%-36.9%). Patients whose asthma control improved over the
      first several months of follow-up experienced significantly (P < .05) fewer
      exacerbations over the subsequent year than patients with initially uncontrolled
      asthma who did not improve. CONCLUSION: Degree of asthma control at one point in
      time is strongly related to the achievement or maintenance of control and to
      asthma exacerbations over time. Patients with uncontrolled asthma, especially
      very poorly controlled asthma, should receive intensive management and follow-up
      in an attempt to achieve well-controlled asthma over time.

PMID- 24565765
TI  - Fever, rash, and systemic symptoms: understanding the role of virus and HLA in
      severe cutaneous drug allergy.
AB  - Drug hypersensitivity syndromes such as abacavir hypersensitivity and the severe
      cutaneous adverse drug reactions have been associated with significant short- and
      long-term morbidity and mortality. More recently, these immunologically mediated
      and previously unpredictable diseases have been shown to be associated with
      primarily class I but also class II HLA alleles. The case of the association of
      HLA-B*57:01 and abacavir hypersensitivity has created a translational roadmap for
      how this knowledge can be used in the clinic to prevent severe reactions.
      Although many hurdles exist to the widespread translation of such HLA screening
      approaches, our understanding of how drugs interact with the major
      histocompatibility complex has contributed to the discovery of new models that
      have provided considerable insights into the immunopathogenesis of severe
      cutaneous adverse drug reactions and other T-cell-mediated drug hypersensitivity
      syndromes. Future translation of this knowledge will facilitate the development
      of preclinical toxicity screening to significantly improve efficacy and safety of
      drug development and design. 

PMID- 24565771
TI  - A novel scoring system to distinguish vocal cord dysfunction from asthma.
AB  - BACKGROUND: Vocal cord dysfunction is often misdiagnosed and mistreated as
      asthma, which can lead to increased and unnecessary medication use and increased
      health care utilization. OBJECTIVE: To develop a valid scoring index that could
      help distinguish vocal cord dysfunction from asthma. METHODS: We compared the
      demographics, comorbidities, clinical symptoms, and symptom triggers of subjects
      with vocal cord dysfunction (n = 89) and those with asthma (n = 59). By using
      multivariable logistic regression, we identified distinguishing features
      associated with vocal cord dysfunction, which were weighted and used to generate
      a novel score. The scoring index also was tested in an independent sample with
      documented vocal cord dysfunction (n = 72). RESULTS: We identified symptoms of
      throat tightness and dysphonia, the absence of wheezing, and the presence of
      odors as a symptom trigger as key features of vocal cord dysfunction that
      distinguish it from asthma. We developed a weighted index based on these
      characteristics, the Pittsburgh Vocal Cord Dysfunction Index. By using a cutoff
      of >=4, this index had good sensitivity (0.83) and specificity (0.95) for the
      diagnosis of vocal cord dysfunction. The scoring index also performed reasonably
      well in the independent convenience sample with laryngoscopy-proven vocal cord
      dysfunction and accurately made the diagnosis in 77.8% of subjects. CONCLUSION:
      The Pittsburgh Vocal Cord Dysfunction Index is proposed as a simple, valid, and
      easy-to-use tool for diagnosing vocal cord dysfunction. If confirmed by a
      prospective evaluation in broader use, it may have significant clinical utility
      by facilitating a timely and accurate diagnosis of vocal cord dysfunction,
      thereby preventing misdiagnosis and mistreatment as asthma. Future prospective
      validation studies will need to be performed.

PMID- 24565772
TI  - The Mastocytosis Society survey on mast cell disorders: patient experiences and
      perceptions.
AB  - BACKGROUND: Mast cell diseases include mastocytosis and mast cell activation
      syndromes, some of which have been shown to involve clonal defects in mast cells
      that result in abnormal cellular proliferation or activation. Numerous clinical
      studies of mastocytosis have been published, but no population-based
      comprehensive surveys of patients in the United States have been identified. Few
      mast cell disease specialty centers exist in the United States, and awareness of
      these mast cell disorders is limited among nonspecialists. Accordingly,
      information concerning the experiences of the overall estimated population of
      these patients has been lacking. OBJECTIVE: To identify the experiences and
      perceptions of patients with mastocytosis, mast cell activation syndromes, and
      related disorders, The Mastocytosis Society (TMS), a US based patient advocacy,
      research, and education organization, conducted a survey of its members and other
      people known or suspected to be part of this patient population. METHODS: A Web
      based survey was publicized through clinics that treat these patients and through
      TMS's newsletter, Web site, and online blogs. Both online and paper copies of the
      questionnaire were provided, together with required statements of consent.
      RESULTS: The first results are presented for 420 patients. These results include
      demographics, diagnoses, symptoms, allergies, provoking factors of mast cell
      symptoms, and disease impact. CONCLUSION: Patients with mastocytosis and mast
      cell activation syndromes have provided clinical specialists, collaborators, and
      other patients with information to enable them to explore and deepen their
      understanding of the experiences and perceptions of people coping with these
      disorders.

PMID- 24565773
TI  - Escalating doses of C1 esterase inhibitor (CINRYZE) for prophylaxis in patients
      with hereditary angioedema.
AB  - BACKGROUND: Nanofiltered C1 inhibitor (human) is approved in the United States
      for routine prophylaxis of angioedema attacks in patients with hereditary
      angioedema, a rare disease caused by a deficiency of functional C1 inhibitor.
      OBJECTIVE: To assess the safety of escalating doses of nanofiltered C1 inhibitor
      (human) in patients who were not adequately controlled on the indicated dose
      (1000 U every 3 or 4 days). METHODS: Eligible patients had >1 attack/month over
      the 3 months before the trial. Doses were escalated to 1500 U every 3 or 4 days
      for 12 weeks, at which point, the patients were evaluated. If treatment was
      successful (<=1 attack/mo) or at the investigator's discretion, the patients
      entered a 3-month follow-up period. The patients with an average of >1
      attack/month were eligible for further escalation to 2000 U and then 2500 U.
      RESULTS: Twenty patients started at 1500 U; 13 were escalated to 2000 U, and 12
      were escalated to 2500 U. Eighteen patients reported adverse events. Two patients
      reported 4 serious adverse events (cerebral cystic hygroma, laryngeal angioedema
      attack, anemia, and bile duct stone) that were considered by investigators to be
      unrelated to treatment. Notably, there were no systemic thrombotic events or
      discontinuations due to adverse events. Fourteen patients were treated
      successfully (70%), continued to the follow-up period at the investigator's
      discretion, or experienced a reduction in attacks of >1.0/month. CONCLUSIONS:
      Dose escalation of nanofiltered C1 inhibitor (human) up to 2500 U was well
      tolerated and reduced attack frequency in the majority of patients.

PMID- 24565774
TI  - Trends in hospitalizations and mortality from asthma in Costa Rica over a 12- to
      15-year period.
AB  - BACKGROUND: Little is known about trends in morbidity and/or mortality due to
      asthma in Latin America. OBJECTIVE: To examine trends in hospitalizations and
      mortality due to asthma from 1997-2000 to 2011 in Costa Rica. METHODS: The rates
      of hospitalization due to asthma were calculated for each sex in 3 age groups
      from 1997 to 2011. The number of deaths due to asthma was first calculated for
      all groups and then for each sex in 3 age groups from 2000 to 2011. All analyses
      were conducted over the entire period and separately for the periods before and
      after a National Asthma Program (NAP) in 2003. Data also were available for
      prescriptions for beclomethasone since 2004. All analyses were conducted by using
      Epi Info. RESULTS: Substantial reductions were found in hospitalizations and
      deaths due to asthma in Costa Ricans (eg, from 25 deaths in 2000 to 5 deaths in
      2011). Although, the percentage decrement in the rates of hospitalization for
      asthma in subjects <20 years old was similar before and after the NAP, the
      reduction in both deaths due to asthma and rates of asthma hospitalizations in
      older subjects were more pronounced after the NAP, when prescriptions for
      beclomethasone were also increased by approximately 129%. CONCLUSION: In Costa
      Rica, there was a marked decrement in hospitalizations and mortality due to
      asthma from 1997-2000 to 2011. In younger subjects, this is likely due to
      guidelines that, since 1988, recommend inhaled corticosteroids for persistent
      asthma. In older adults, the NAP probably enhanced reductions in hospitalizations
      and deaths due to asthma through inhaled corticosteroid use.

PMID- 24565776
TI  - Oral immunotherapy for the treatment of peanut allergy: is it ready for prime
      time?

PMID- 24565775
TI  - Oral immunotherapy for peanut allergy: multipractice experience with epinephrine
      treated reactions.
AB  - BACKGROUND: Peanut allergy creates the risk of life-threatening anaphylaxis that
      can disrupt psychosocial development and family life. The avoidance management
      strategy often fails to prevent anaphylaxis and may contribute to social
      dysfunction. Peanut oral immunotherapy may address these problems, but there are
      safety concerns regarding implementation in clinical practice. OBJECTIVE: The
      purpose of this report is to communicate observations about the frequency of
      epinephrine-treated reactions during peanut oral immunotherapy in 5 different
      allergy/immunology practices. METHODS: Retrospective chart review of peanut oral
      immunotherapy performed in 5 clinical allergy practices. RESULTS: A total of 352
      treated patients received 240,351 doses of peanut, peanut butter, or peanut
      flour, and experienced 95 reactions that were treated with epinephrine. Only 3
      patients received 2 doses of epinephrine, and no patient required more intensive
      treatment. A total of 298 patients achieved the target maintenance dose for a
      success rate of 85%. CONCLUSION: Peanut oral immunotherapy carries a risk of
      systemic reactions. In the context of oral immunotherapy, those reactions were
      recognized and treated promptly. Peanut oral immunotherapy may be a suitable
      therapy for patients managed by qualified allergists/immunologists.

PMID- 24565777
TI  - A case of exuberant candidal onychomycosis in a child with hyper IgE syndrome.

PMID- 24565778
TI  - Successful rapid intravenous desensitization for radioiodine contrast allergy in
      a patient requiring urgent coronary angiography.

PMID- 24565779
TI  - Doxycycline desensitization for a suspected case of ehrlichiosis.

PMID- 24565780
TI  - Successful carboplatin desensitization by using omalizumab and paradoxical
      diminution of total IgE levels.

PMID- 24565782
TI  - Unexpected decrease in total IgE in a patient with allergic bronchopulmonary
      aspergillosis treated with omalizumab.

PMID- 24565781
TI  - Clinical and laboratory improvement after intravenous immunoglobulin in drug
      reaction with eosinophilia and systemic symptoms.

PMID- 24565784
TI  - Desensitization to chemotherapeutic agents.

PMID- 24565783
TI  - A pediatric case of chronic idiopathic urticaria induced by antihistamines.

PMID- 24565785
TI  - Omalizumab for chronic urticaria.

PMID- 24565788
TI  - Lazy random walks for superpixel segmentation.
AB  - We present a novel image superpixel segmentation approach using the proposed lazy
      random walk (LRW) algorithm in this paper. Our method begins with initializing
      the seed positions and runs the LRW algorithm on the input image to obtain the
      probabilities of each pixel. Then, the boundaries of initial superpixels are
      obtained according to the probabilities and the commute time. The initial
      superpixels are iteratively optimized by the new energy function, which is
      defined on the commute time and the texture measurement. Our LRW algorithm with
      self-loops has the merits of segmenting the weak boundaries and complicated
      texture regions very well by the new global probability maps and the commute time
      strategy. The performance of superpixel is improved by relocating the center
      positions of superpixels and dividing the large superpixels into small ones with
      the proposed optimization algorithm. The experimental results have demonstrated
      that our method achieves better performance than previous superpixel approaches.

PMID- 24565789
TI  - A unified data embedding and scrambling method.
AB  - Conventionally, data embedding techniques aim at maintaining high-output image
      quality so that the difference between the original and the embedded images is
      imperceptible to the naked eye. Recently, as a new trend, some researchers
      exploited reversible data embedding techniques to deliberately degrade image
      quality to a desirable level of distortion. In this paper, a unified data
      embedding-scrambling technique called UES is proposed to achieve two objectives
      simultaneously, namely, high payload and adaptive scalable quality degradation.
      First, a pixel intensity value prediction method called checkerboard-based
      prediction is proposed to accurately predict 75% of the pixels in the image based
      on the information obtained from 25% of the image. Then, the locations of the
      predicted pixels are vacated to embed information while degrading the image
      quality. Given a desirable quality (quantified in SSIM) for the output image, UES
      guides the embedding-scrambling algorithm to handle the exact number of pixels,
      i.e., the perceptual quality of the embedded-scrambled image can be controlled.
      In addition, the prediction errors are stored at a predetermined precision using
      the structure side information to perfectly reconstruct or approximate the
      original image. In particular, given a desirable SSIM value, the precision of the
      stored prediction errors can be adjusted to control the perceptual quality of the
      reconstructed image. Experimental results confirmed that UES is able to perfectly
      reconstruct or approximate the original image with SSIM value > 0.99 after
      completely degrading its perceptual quality while embedding at 7.001 bpp on
      average.

PMID- 24565790
TI  - Saliency prediction on stereoscopic videos.
AB  - We describe a new 3D saliency prediction model that accounts for diverse low
      level luminance, chrominance, motion, and depth attributes of 3D videos as well
      as high-level classifications of scenes by type. The model also accounts for
      perceptual factors, such as the nonuniform resolution of the human eye,
      stereoscopic limits imposed by Panum's fusional area, and the predicted degree of
      (dis) comfort felt, when viewing the 3D video. The high-level analysis involves
      classification of each 3D video scene by type with regard to estimated camera
      motion and the motions of objects in the videos. Decisions regarding the relative
      saliency of objects or regions are supported by data obtained through a series of
      eye-tracking experiments. The algorithm developed from the model elements
      operates by finding and segmenting salient 3D space-time regions in a video, then
      calculating the saliency strength of each segment using measured attributes of
      motion, disparity, texture, and the predicted degree of visual discomfort
      experienced. The saliency energy of both segmented objects and frames are
      weighted using models of human foveation and Panum's fusional area yielding a
      single predictor of 3D saliency.

PMID- 24565791
TI  - Progressive image denoising through hybrid graph Laplacian regularization: a
      unified framework.
AB  - Recovering images from corrupted observations is necessary for many real-world
      applications. In this paper, we propose a unified framework to perform
      progressive image recovery based on hybrid graph Laplacian regularized
      regression. We first construct a multiscale representation of the target image by
      Laplacian pyramid, then progressively recover the degraded image in the scale
      space from coarse to fine so that the sharp edges and texture can be eventually
      recovered. On one hand, within each scale, a graph Laplacian regularization model
      represented by implicit kernel is learned, which simultaneously minimizes the
      least square error on the measured samples and preserves the geometrical
      structure of the image data space. In this procedure, the intrinsic manifold
      structure is explicitly considered using both measured and unmeasured samples,
      and the nonlocal self-similarity property is utilized as a fruitful resource for
      abstracting a priori knowledge of the images. On the other hand, between two
      successive scales, the proposed model is extended to a projected high-dimensional
      feature space through explicit kernel mapping to describe the interscale
      correlation, in which the local structure regularity is learned and propagated
      from coarser to finer scales. In this way, the proposed algorithm gradually
      recovers more and more image details and edges, which could not been recovered in
      previous scale. We test our algorithm on one typical image recovery task: impulse
      noise removal. Experimental results on benchmark test images demonstrate that the
      proposed method achieves better performance than state-of-the-art algorithms.

PMID- 24565793
TI  - VDAC electronics: 2. A new, anaerobic mechanism of generation of the membrane
      potentials in mitochondria.
AB  - Mitochondrial hexokinase (HK) and creatine kinase (CK) known to form complexes
      with a voltage dependent anion channel (VDAC) have been reported to increase cell
      death resistance under hypoxia/anoxia. In this work we propose a new, non
      Mitchell mechanism of generation of the inner and outer membrane potentials at
      anaerobic conditions. The driving force is provided by the Gibbs free energy of
      the HK and CK reactions associated with the VDAC-HK and the ANT (adenine
      nucleotide translocator)-CK-VDAC complexes, respectively, both functioning as
      voltage generators. In the absence of oxygen, the cytosolic creatine phosphate
      can be directly used by the ANT-CK-VDAC contact sites to produce ATP from ADP in
      the mitochondrial matrix. After that, ATP released through the fraction of
      unbound ANTs in exchange for ADP is used in the mitochondrial intermembrane space
      by the outer membrane VDAC-HK electrogenic complexes to convert cytosolic glucose
      into glucose-6-phosphate. A simple computational model based on the application
      of Ohm's law to an equivalent electrical circuit showed a possibility of
      generation of the inner membrane potential up to -160mV, under certain
      conditions, and of relatively high outer membrane potential without wasting of
      ATP that normally leads to cell death. The calculated membrane potentials
      depended on the restriction of ATP/ADP diffusion in narrow cristae and through
      the cristae junctions. We suggest that high inner membrane potential and calcium
      extrusion from the mitochondrial intermembrane space by generated positive outer
      membrane potential prevent mitochondrial permeability transition, thus allowing
      the maintenance of mitochondrial integrity and cell survival in the absence of
      oxygen. 

PMID- 24565792
TI  - Effect of recurrent yohimbine on immediate and post-hoc behaviors, stress
      hormones, and energy homeostatic parameters.
AB  - Evidence from experimental models has suggested that acute activation of brain
      stress and anxiety pathways impacts subsequent behaviors that are mediated or
      modulated by limbic circuitry. There have been limited investigations of prior or
      chronic activation of these pathways on subsequent limbic-mediated behaviors. In
      this study, we tested whether recurrent administration of the anxiogenic compound
      yohimbine (YOH) could have post-injection effects on brain activation, stress
      hormones, and performance in sucrose self-administration and startle response
      paradigms. Rats received six injections across two weeks of either 2mg/kg YOH or
      saline. Behavioral evaluation confirmed the continued efficacy of the YOH
      regimen, and increased adrenal corticosterone (CORT) was observed. Several days
      following YOH or SAL administration, cFos, CORT and adrenocorticotropin hormone
      (ACTH), and behavioral performance were measured. cFos was elevated post-YOH in
      the hippocampus; ventral tegmental area/zona inserta; and central and medial
      nuclei of the amygdala. This activation is consistent with a sustained effect of
      YOH to activate fear and anxiety circuitries in the CNS. CORT but not ACTH was
      elevated in the YOH-rats following startle testing. Self-administration and
      startle tests suggested an increase of non-specific activity in the post-YOH
      rats; there was no increase in sucrose self-administration or startle response
      per se. Our findings suggest that recurrent YOH administration may prove a useful
      and reliable model for simulating recurrent stress/anxiety, and that enhancements
      to the paradigm such as higher or more frequent dosing of YOH could yield
      stronger or more extensive behavioral effects. 

PMID- 24565794
TI  - The effect of the chain length distribution of free fatty acids on the mixing
      properties of stratum corneum model membranes.
AB  - The stratum corneum (SC) plays a fundamental role in the barrier function of the
      skin. The SC consists of corneocytes embedded in a lipid matrix. The main lipid
      classes in the lipid matrix are ceramides (CERs), cholesterol (CHOL) and free
      fatty acids (FFAs). The aim of this study was to examine the effect of the chain
      length of FFAs on the thermotropic phase behavior and mixing properties of SC
      lipids. Fourier transform infrared spectroscopy and Raman imaging spectroscopy
      were used to study the mixing properties using either protonated or deuterated
      FFAs. We selected SC model lipid mixtures containing only a single CER, CHOL and
      either a single FFA or a mixture of FFAs mimicking the FFA SC composition. The
      single CER consists of a sphingoid base with 18 carbon atoms and an acyl chain
      with a chain length of 24 carbon atoms. When using lignoceric acid (24 carbon
      atoms) or a mixture of FFAs, the CER and FFAs participated in mixed crystals, but
      hydration of the mixtures induced a slight phase separation between CER and FFA.
      The mixed crystalline structures did not phase separate during storage even up to
      a time period of 3months. When using palmitic acid (16 carbon atoms), a slight
      phase separation was observed between FFA and CER. This phase separation was
      clearly enhanced during hydration and storage. In conclusion, the thermotropic
      phase behavior and the mixing properties of the SC lipid mixtures were shown to
      strongly depend on the chain length and chain length distribution of FFAs, while
      hydration enhanced the phase separation. 

PMID- 24565795
TI  - Studies on the regulation of lipid biosynthesis in plants: application of control
      analysis to soybean.
AB  - Although there is much knowledge of the enzymology (and genes coding the
      proteins) of lipid biosynthesis in higher plants, relatively little attention has
      been paid to regulation. We have demonstrated the important role for
      cholinephosphate cytidylyltransferase in the biosynthesis of the major extra
      plastidic membrane lipid, phosphatidylcholine. We followed this work by applying
      control analysis to light-induced fatty acid synthesis. This was the first such
      application to lipid synthesis in any organism. The data showed that acetyl-CoA
      carboxylase was very important, exerting about half of the total control. We then
      applied metabolic control analysis to lipid accumulation in important oil crops -
      oilpalm, olive, and rapeseed. Recent data with soybean show that the block of
      fatty acid biosynthesis reactions exerts somewhat more control (63%) than lipid
      assembly although both are clearly very important. These results suggest that
      gene stacks, targeting both parts of the overall lipid synthesis pathway will be
      needed to increase significantly oil yields in soybean. This article is part of a
      Special Issue entitled: Membrane Structure and Function: Relevance in the Cell's
      Physiology, Pathology and Therapy. 

PMID- 24565796
TI  - Comprehensive portrait of cholesterol containing oxidized membrane.
AB  - Biological membranes are under significant oxidative stress caused by reactive
      oxygen species mostly originating during cellular respiration. Double bonds of
      the unsaturated lipids are most prone to oxidation, which might lead to
      shortening of the oxidized chain and inserting of terminal either aldehyde or
      carboxylic group. Structural rearrangement of oxidized lipids, addressed already,
      is mainly associated with looping back of the hydrophilic terminal group. This
      contribution utilizing dual-focus fluorescence correlation spectroscopy and
      electron paramagnetic resonance as well as atomistic molecular dynamics
      simulations focuses on the overall changes of the membrane structural and
      dynamical properties once it becomes oxidized. Particularly, attention is paid to
      cholesterol rearrangement in the oxidized membrane revealing its preferable
      interaction with carbonyls of the oxidized chains. In this view cholesterol seems
      to have a tendency to repair, rather than condense, the bilayer. 

PMID- 24565798
TI  - The antibacterial properties and biocompatibility of a Ti-Cu sintered alloy for
      biomedical application.
AB  - The antibacterial activity, the cytotoxicity and the cell function of a sintered
      Ti-10 wt% Cu alloy were investigated in order to assess the suitability of the
      alloy for biomedical application. The antibacterial activity of the alloy was
      investigated by a plate-count method and the cytotoxicity was studied by
      examining the MG63 cell response by CCK8 assessment. The cell function was
      monitored by measuring the AKP activity. The Cu ion released from the Ti-Cu alloy
      was also measured by an inductively coupled plasma spectrometer at different
      immersion durations. The results show that the antibacterial rates of the alloy
      against Escherichia coli and Staphylococcus aureus increase with an increase in
      the incubation duration. After 7 h of incubation, the alloy showed an
      antibacterial rate of 91.66% against S. aureus and 99. 01% against E. coli. With
      a further extension of incubation time to 24 h, the antibacterial rate increased
      to 100% against S. aureus and 99.93% against E. coli. No cytotoxicity was
      observed on the alloy by a CKK8 test during three days of incubation in
      comparison with commercially available pure titanium (cp-Ti). AKP test results
      showed a significantly high AKP value (p = 0.001 < 0.01) on the Ti-Cu alloy on
      day 1. The Cu ion release was thought to contribute to the strong antibacterial
      property, but the Cu ion did not lead to cell cytotoxicity. Strong antibacterial
      activity and good cell biocompatibility suggest that the Ti-Cu alloy could reduce
      bacterial infection and have a potential application as an implant material.

PMID- 24565799
TI  - Humic substances interfere with phosphate removal by Lanthanum modified clay in
      controlling eutrophication.
AB  - The lanthanum (La) modified bentonite Phoslock((r)) has been proposed as
      dephosphatisation technique aiming at removing Filterable Reactive Phosphorus
      (FRP) from the water and blocking the release of FRP from the sediment. In the
      modified clay La is expected the active ingredient. We conducted controlled
      laboratory experiments to measure the FRP removal by Phoslock((r)) in the
      presence and absence of humic substances, as La complexation with humic
      substances might lower the effectiveness of La (Phoslock((r))) to bind FRP. The
      results of our study support the hypothesis that the presence of humic substances
      can interfere with the FRP removal by the La-modified bentonite. Both a short
      term (1 d) and long-term (42 d) experiment were in agreement with predictions
      derived from chemical equilibrium modelling and showed lower FRP removal in
      presence of humic substances. This implies that in DOC-rich inland waters the
      applicability of exclusively Phoslock((r)) as FRP binder should be met
      critically. In addition, we observed a strong increase of filterable La in
      presence of humic substances reaching in a week more than 270 MUg La l(-1) that
      would infer a violation of the Dutch La standard for surface water, which is 10.1
      MUg La l(-1). Hence, humic substances are an important factor that should be
      given attention when considering chemical FRP inactivation as they might play a
      substantial role in lowering the efficacy of metal-based FRP-sorbents, which
      makes measurements of humic substances (DOC) as well as controlled experiments
      vital. 

PMID- 24565797
TI  - Branched amphiphilic peptide capsules: cellular uptake and retention of
      encapsulated solutes.
AB  - Branched amphiphilic peptide capsules (BAPCs) are peptide nano-spheres comprised
      of equimolar proportions of two branched peptide sequences bis(FLIVI)-K-KKKK and
      bis(FLIVIGSII)-K-KKKK that self-assemble to form bilayer delimited capsules. In
      two recent publications we described the lipid analogous characteristics of our
      BAPCs, examined their initial assembly, mode of fusion, solute encapsulation, and
      resizing and delineated their capability to be maintained at a specific size by
      storing them at 4 degrees C. In this report we describe the stability, size
      limitations of encapsulation, cellular localization, retention and, bio
      distribution of the BAPCs in vivo. The ability of our constructs to retain alpha
      particle emitting radionuclides without any apparent leakage and their
      persistence in the peri-nuclear region of the cell for extended periods of time,
      coupled with their ease of preparation and potential tune-ability, makes them
      attractive as biocompatible carriers for targeted cancer therapy using particle
      emitting radioisotopes. This article is part of a Special Issue entitled:
      Interfacially Active Peptides and Proteins. Guest Editors: William C. Wimley and
      Kalina Hristova. 

PMID- 24565800
TI  - Removal of micropollutants during tertiary wastewater treatment by biofiltration:
      Role of nitrifiers and removal mechanisms.
AB  - The objective of this study was to determine the extent to which a suite of
      organic micropollutants (MPs) can be removed by biological filtration and the
      role of bioavailability and ammonia oxidizing microorganisms (AOMs) in the
      biodegradation process. During approximately one year, laboratory-scale columns
      with 8 min empty bed contact time (EBCT) and packed with anthracite as filter
      media were used for treating a tertiary effluent spiked with a broad range of MPs
      at a target concentration of 2 MUg L(-1). In parallel columns, aerobic biomass
      growth was inhibited by using either the biocide sodium azide (500 mg L(-1) NaN3)
      or allylthiourea (5 mg L(-1) ATU), specifically inhibiting nitrifying bacteria.
      Once the biomass had colonized the media, around 15% of the dissolved organic
      carbon (DOC) contained in the untreated tertiary effluent was removed by non
      inhibited columns. The removal of several MPs increased over time indicating the
      relevance of biological activity for the removal of MPs, while the negative
      control, the NaN3 inhibited column, showed no significant removal. Out of 33 MPs,
      19 were recalcitrant (<25%) to biodegradation under aerobic conditions with the
      others exhibiting a diverse range of removal efficiency up to 95%. Through
      inhibition by ATU it was shown that nitrifying bacteria were clearly having a
      role in the degradation of several MPs, whereas the removal of other MPs was not
      affected by the presence of the nitrification inhibitor. A relationship between
      the qualitative assessment of sorption of MPs on granular activated carbon (GAC)
      and their removal efficiency by biodegradation on anthracite was observed. This
      result suggested that the affinity of the MPs for GAC media could be a useful
      indicator of the bioavailability of compounds during biofiltration on anthracite.

PMID- 24565801
TI  - The bacteriological composition of biomass recovered by flushing an operational
      drinking water distribution system.
AB  - This study investigates the influence of pipe characteristics on the
      bacteriological composition of material mobilised from a drinking water
      distribution system (DWDS) and the impact of biofilm removal on water quality.
      Hydrants in a single UK Distribution Management Area (DMA) with both polyethylene
      and cast iron pipe sections were subjected to incremental increases in flow to
      mobilise material from the pipe walls. Turbidity was monitored during these
      operations and water samples were collected for physico-chemical and
      bacteriological analysis. DNA was extracted from the material mobilised into the
      bulk water before and during flushing. Bacterial tag-encoded 454 pyrosequencing
      was then used to characterize the bacterial communities present in this material.
      Turbidity values were high in the samples from cast iron pipes. Iron, aluminium,
      manganese and phosphate concentrations were found to correlate to observed
      turbidity. The bacterial community composition of the material mobilised from the
      pipes was significantly different between plastic and cast iron pipe sections (p
      < 0.5). High relative abundances of Alphaproteobacteria (23.3%), Clostridia
      (10.3%) and Actinobacteria (10.3%) were detected in the material removed from
      plastic pipes. Sequences related to Alphaproteobacteria (22.8%), Bacilli (16.6%),
      and Gammaproteobacteria (1.4%) were predominant in the samples obtained from cast
      iron pipes. The highest species richness and diversity were found in the samples
      from material mobilised from plastic pipes. Spirochaeta spp., Methylobacterium
      spp. Clostridium spp. and Desulfobacterium spp., were the most represented genera
      in the material obtained prior to and during the flushing of the plastic pipes.
      In cast iron pipes a high relative abundance of bacteria able to utilise
      different iron and manganese compounds were found such as Lysinibacillus spp.,
      Geobacillus spp. and Magnetobacterium spp. 

PMID- 24565802
TI  - Removal of multiple electron acceptors by pilot-scale, two-stage membrane biofilm
      reactors.
AB  - We studied the performance of a pilot-scale membrane biofilm reactor (MBfR)
      treating groundwater containing four electron acceptors: nitrate (NO3(-)),
      perchlorate (ClO4(-)), sulfate (SO4(2-)), and oxygen (O2). The treatment goal was
      to remove ClO4(-) from ~200 MUg/L to less than 6 MUg/L. The pilot system was
      operated as two MBfRs in series, and the positions of the lead and lag MBfRs were
      switched regularly. The lead MBfR removed at least 99% of the O2 and 63-88% of
      NO3(-), depending on loading conditions. The lag MBfR was where most of the ClO4(
      ) reduction occurred, and the effluent ClO4(-) concentration was driven to as low
      as 4 MUg/L, with most concentrations <=10 MUg/L. However, SO4(2-) reduction
      occurred in the lag MBfR when its NO3(-) + O2 flux was smaller than ~0.18 g
      H2/m(2)-d, and this was accompanied by a lower ClO4(-) flux. We were able to
      suppress SO4(2-) reduction by lowering the H2 pressure and increasing the NO3(-)
      + O2 flux. We also monitored the microbial community using the quantitative
      polymerase chain reaction targeting characteristic reductase genes. Due to
      regular position switching, the lead and lag MBfRs had similar microbial
      communities. Denitrifying bacteria dominated the biofilm when the NO3(-) + O2
      fluxes were highest, but sulfate-reducing bacteria became more important when
      SO4(2-) reduction was enhanced in the lag MBfR due to low NO3(-) + O2 flux. The
      practical two-stage strategy to achieve complete ClO4(-) and NO3(-) reduction
      while suppressing SO4(2-) reduction involved controlling the NO3(-) + O2 surface
      loading between 0.18 and 0.34 g H2/m(2)-d and using a low H2 pressure in the lag
      MBfR. 

PMID- 24565803
TI  - Hydrophilic fraction of natural organic matter causing irreversible fouling of
      microfiltration and ultrafiltration membranes.
AB  - Although membrane filtration is a promising technology in the field of drinking
      water treatment, persistent membrane fouling remains a major disadvantage. For
      more efficient operation, causative agents of membrane fouling need to be
      identified. Membrane fouling can be classified into physically reversible and
      irreversible fouling on basis of the removability of the foulants by physical
      cleaning. Four types of natural organic matter (NOM) in river water used as a
      source of drinking water were fractionated into hydrophobic and hydrophilic
      fractions, and their potential to develop irreversible membrane fouling was
      evaluated by a bench-scale filtration experiment together with spectroscopic and
      chromatographic analyses. In this study, only dissolved NOM was investigated
      without consideration of interactions of NOM fractions with particulate matter.
      Results demonstrated that despite identical total organic carbon (TOC), fouling
      development trends were significantly different between hydrophilic and
      hydrophobic fractions. The hydrophobic fractions did not increase membrane
      resistance, while the hydrophilic fractions caused severe loss of membrane
      permeability. These results were identical with the case when the calcium was
      added to hydrophobic and hydrophilic fractions. The largest difference in NOM
      characteristics between hydrophobic and hydrophilic fractions was the presence or
      absence of macromolecules; the primary constituent causing irreversible fouling
      was inferred to be "biopolymers", including carbohydrates and proteins. In
      addition, the results demonstrated that the extent of irreversible fouling was
      considerably different depending on the combination of membrane materials and NOM
      characteristics. Despite identical nominal pore size (0.1 MUm), a polyvinylidene
      fluoride (PVDF) membrane was found to be more rapidly fouled than a PE membrane.
      This is probably explained by the generation of strong hydrogen bonding between
      hydroxyl groups of biopolymers and fluorine of the PVDF membrane. On the basis of
      these findings, it was suggested that the higher fouling potential of the
      hydrophilic fraction of the dissolved NOMs from various natural water sources are
      mainly attributed to macromolecules, or biopolymers. 

PMID- 24565805
TI  - Morphological classification of bioaerosols from composting using scanning
      electron microscopy.
AB  - This research classifies the physical morphology (form and structure) of
      bioaerosols emitted from open windrow composting. Aggregation state, shape and
      size of the particles captured are reported alongside the implications for
      bioaerosol dispersal after release. Bioaerosol sampling took place at a
      composting facility using personal air filter samplers. Samples were analysed
      using scanning electron microscopy. Particles were released mainly as small (<1
      MUm) single, spherical cells, followed by larger (>1 MUm) single cells, with
      aggregates occurring in smaller proportions. Most aggregates consisted of
      clusters of 2-3 particles as opposed to chains, and were <10 MUm in size. No
      cells were attached to soil debris or wood particles. These small single cells or
      small aggregates are more likely to disperse further downwind from source, and
      cell viability may be reduced due to increased exposure to environmental factors.

PMID- 24565804
TI  - Microbial community structure and function of nitrobenzene reduction biocathode
      in response to carbon source switchover.
AB  - The stress of poised cathode potential condition and carbon source switchover for
      functional biocathode microbial community influences is poorly understood. Using
      high-throughput functional gene array (GeoChip v4.2) and Illumina 16S rRNA gene
      MiSeq sequencing, we investigated the phylogenetic and functional microbial
      community of the initial inoculum and biocathode for bioelectrochemical reduction
      of nitrobenzene to less toxic aniline in response to carbon source switchover
      (from organic glucose to inorganic bicarbonate). Selective transformation of
      nitrobenzene to aniline maintained in the bicarbonate fed biocathode although
      nitrobenzene reduction rate and aniline formation rate were significantly
      decreased compared to those of the glucose-fed biocathode. When the electrical
      circuit of the glucose-fed biocathode was disconnected, both rates of
      nitrobenzene reduction and of aniline formation were markedly decreased,
      confirming the essential role of an applied electric field for the enhancement of
      nitrobenzene reduction. The stress of poised cathode potential condition led to
      clear succession of microbial communities from the initial inoculum to biocathode
      and the carbon source switchover obviously changed the microbial community
      structure of biocathode. Most of the dominant genera were capable of reducing
      nitroaromatics to the corresponding aromatic amines regardless of the performance
      mode. Heterotrophic Enterococcus was dominant in the glucose-fed biocathode while
      autotrophic Paracoccus and Variovorax were dominant in the bicarbonate-fed
      biocathode. Relatively higher intensity of diverse multi-heme cytochrome c
      (putatively involved in electrons transfer) and carbon fixation genes was
      observed in the biocarbonate-fed biocathode, likely met the requirement of the
      energy conservation and maintained the nitrobenzene selective reduction
      capability after carbon source switchover. Extracellular pilin, which are
      important for biofilm formation and potential conductivity, had a higher gene
      abundance in the glucose-fed biocathode might explain the enhancement of electro
      catalysis activity for nitrobenzene reduction with glucose supply. Dominant
      nitroaromatics-reducing or electrochemically active bacteria and diverse
      functional genes related to electrons transfer and nitroaromatics reduction were
      associated with nitrobenzene reduction efficiency of biocathode communities in
      response to carbon source switchover. 

PMID- 24565806
TI  - Effect of a Kinect-based exercise game on improving executive cognitive
      performance in community-dwelling elderly: case control study.
AB  - BACKGROUND: Decrease of dual-task (DT) ability is known to be one of the risk
      factors for falls. We developed a new game concept, Dual-Task Tai Chi (DTTC),
      using Microsoft's motion-capture device Kinect, and demonstrated that the DTTC
      test can quantitatively evaluate various functions that are known risk factors
      for falling in elderly adults. Moreover, DT training has been attracting
      attention as a way to improve balance and DT ability. However, only a few studies
      have reported that it improves cognitive performance. OBJECTIVE: The purpose of
      this study was to demonstrate whether or not a 12-week program of DTTC training
      would effectively improve cognitive functions. METHODS: This study examined
      cognitive functions in community-dwelling older adults before and after 12 weeks
      of DTTC training (training group [TG]) or standardized training (control group
      [CG]). Primary end points were based on the difference in cognitive functions
      between the TG and the CG. Cognitive functions were evaluated using the trail
      making test (part A and part B) and verbal fluency test. RESULTS: A total of 41
      elderly individuals (TG: n=26, CG: n=15) participated in this study and their
      cognitive functions were assessed before and after DTTC training. Significant
      differences were observed between the two groups with significant group * time
      interactions for the executive cognitive function measure, the delta-trail-making
      test (part B-part A; F1,36=4.94, P=.03; TG: pre mean 48.8 [SD 43.9], post mean
      42.2 [SD 29.0]; CG: pre mean 49.5 [SD 51.8], post mean 64.9 [SD 54.7]).
      CONCLUSIONS: The results suggest that DTTC training is effective for improving
      executive cognitive functions. TRIAL REGISTRATION: Japan Medical Association
      Clinical Trial Registration Number: JMA-IIA00092;
      https://dbcentre3.jmacct.med.or.jp/jmactr/App/JMACTRS06/JMACTRS06.aspx?seqno=2682
      (Archived by WebCite at http://www.webcitation.org/6NRtOkZFh).

PMID- 24565807
TI  - Recruiting competent newly qualified nurses in the London region: An exploratory
      study.
AB  - AIM: This paper reports a study commissioned to address concerns that not all
      newly qualified nurses (NQNs) were perceived to be competent at the point of
      appointment to their first post. It seeks to understand how competence is
      interpreted in the context of selection and recruitment, and explore the
      different expectations and experiences of employing Trusts across the London
      region. BACKGROUND: Competence is a significant topic in nursing and there is
      much literature around the concept, what it means and how it relates to
      behaviours and values with no universally accepted definition. However, there
      appears to be little evidence about how competence is assessed in practice in the
      selection and recruitment of NQNs to their first post. METHODS: The study took a
      three-phase, mixed method approach including a literature review, an electronic
      survey to map current assessment and selection procedures, and focus groups to
      identify the competencies perceived essential by senior nurses. FINDINGS: Most
      Trusts reported assessing core competencies, and could report how they do this
      with respect to literacy and numeracy. Employers could describe what they
      required from NQNs, and how applicants both met and did not meet expectations.
      Several personal attributes were considered as important as key competences, but
      these are not described in the KSF or NMC frameworks, and it is not clear how
      these are assessed in selection processes. CONCLUSION: There appeared to be a
      large variation in the number and types of competence assessments being used for
      recruitment, with little consistency in the detail of the assessments, although
      broadly similar assessment exercises are used. There appears to be little
      evidence as to the validity of the measures being used and whether in fact they
      are measuring the competences that are being sought or considered most important.
      It would appear that practical skills are more easily assessable, but there is a
      lack of clarity regarding the assessment of those competences that are considered
      equally important but appear to be more elusive to assessment such as
      communication and teamwork. It is also unclear how a number of 'personal
      qualities' described as essential for NQNs are being assessed at recruitment.

PMID- 24565808
TI  - Factors influencing partnerships between higher education and healthcare.
AB  - OBJECTIVE: The aim of this study was to describe the factors influencing
      partnerships between higher education and healthcare. BACKGROUND: Partnerships
      have often been studied as organisations' internal processes or multi
      professional team activities. However, there has been less research on the
      partnership as a phenomenon between organisations and, until now, the research
      has mainly focused on experiences in the US and the UK. SETTING, PARTICIPANTS AND
      METHODS: The study was carried out in Finland. Staff from a university of applied
      sciences and a service unit for the elderly took part in nine focus group
      interviews (n=39) and produced self-evaluations based on diaries (n=13) and
      essays (n=24). The data were analysed by qualitative content analysis. RESULTS:
      The factors influencing partnerships were: a joint development target, agreeing
      on collaboration, providing resources for partnership, enhancing mutual
      understanding, sharing operational culture, commitment and participatory change
      management and communication. CONCLUSIONS: This study updates, and complements,
      previous reviews on factors influencing partnerships, by providing some new
      concepts and a new cultural perspective from Finland on a partnership between
      higher education and healthcare. The results provide information on factors that
      influence partnerships and develop and manage their sustainability.

PMID- 24565809
TI  - Functional expression of electron transport chain complexes in mouse rod outer
      segments.
AB  - Rod photoreceptors efficiently carry out phototransduction cascade, an
      energetically costly process. Our recent data in bovine rod outer segment (OS)
      demonstrated that ATP for phototransduction is produced by an extramitochondrial
      oxidative phosphorylation, thanks to the expression of the Electron Transport
      Chain (ETC) complexes and of F1Fo ATP synthase in disks. Here we have focused on
      mouse retinas, reporting the activity of ETC complexes I, II, IV assayed directly
      on unfixed mouse eye sections, as well as immunogold TEM analysis of fixed mouse
      eye sections to verify the presence of ND4L subunit of ETC complex I and subunit
      IV of ETC complex IV in rod OS. Data suggest the presence of functional ETC in
      mouse rod OS, like their bovine counterpart. The protocol here developed for in
      situ assay of the ETC complexes activity represents a reliable method for the
      detection of ETC dysfunction in mice models of retinal pathologies. In fact, the
      ETC is a major source of reactive oxygen intermediates, and oxidative stress,
      especially when ectopically expressed in the OS. In turn, oxidative stress
      contributes to many retinal pathologies, such as diabetic retinopathy, age
      related macular degeneration, photoreceptor death after retinal detachment and
      some forms of retinitis pigmentosa.

PMID- 24565810
TI  - Dynamic expression of novel and conserved microRNAs and their targets in diploid
      and tetraploid of Paulownia tomentosa.
AB  - MicroRNAs (miRNAs) play profound roles in plant growth and development by
      regulating gene expression. Tetraploid plants often have better physical
      characteristics and stress tolerance than their diploid progenitors, but the role
      of miRNAs in this superiority is unclear. Paulownia tomentosa, (Paulowniaceae) is
      attracting research attention in China because of its rapid development, wide
      distribution, and potential economic uses. To identify miRNAs at the
      transcriptional level in P. tomentosa, Illumina sequencing was used to sequence
      the libraries of diploid and tetraploid plants. Sequence analysis identified 37
      conserved miRNAs belonging to 14 miRNA families and 14 novel miRNAs belonging to
      seven miRNA families. Among the miRNAs, 16 conserved miRNAs from 11 families and
      five novel miRNAs were differentially expressed in the tetraploid and diploid;
      most were more strongly expressed in the former. The miRNA target genes and their
      functions were identified and discussed. The results showed that several P.
      tomentosa miRNAs may play important roles in the improved traits seen in
      tetraploids. This study provides a foundation for understanding the regulatory
      mechanisms of miRNAs in tetraploid trees.

PMID- 24565811
TI  - Ribonuclease binase decreases destructive changes of the liver and restores its
      regeneration potential in mouse lung carcinoma model.
AB  - The successful application of exogenous ribonucleases of different origin to
      suppress tumor growth allows one to consider them as perspective therapeutics for
      treatment of oncological diseases. An important aspect of the success of an anti
      cancer drug is low hepatotoxicity, which will reduce, if not eliminate entirely
      the undesirable side effects of treatment. Previously we have shown that
      ribonuclease from Bacillus intermedius (binase) exhibits high antitumor and
      antimetastatic activity in tumor models of different histological origin. In this
      work we studied hepatotoxic action of binase using mouse tumor model of Lewis
      lung carcinoma. Binase at doses of 0.1-1 mg/kg which produced effective
      suppression of tumor growth and metastasis, showed positive effect on the liver
      of tumor-bearing mice expressed in a significant reduction in the volume of
      destructive changes in the liver parenchyma and return to the normal level of the
      liver regenerative potential impaired due to endogenous intoxication and tumor
      burden.

PMID- 24565812
TI  - The repair of environmentally relevant DNA double strand breaks caused by high
      linear energy transfer irradiation--no simple task.
AB  - High linear energy transfer (LET) ionising radiation (IR) such as radon-derived
      alpha particles and high mass, high energy (HZE) particles of cosmic radiation
      are the predominant forms of IR to which humanity is exposed throughout life.
      High-LET forms of IR are established carcinogens relevant to human cancer, and
      their potent mutagenicity is believed, in part, to be due to a greater incidence
      of clustered DNA double strand breaks (DSBs) and associated lesions, as
      ionization events occur within a more confined genomic space. The repair of such
      DNA damage is now well-documented to occur with slower kinetics relative to that
      induced by low-LET IR, and to be more reliant upon homology-directed repair
      pathways. Underlying these phenomena is the relative inability of non-homologous
      end-joining (NHEJ) to adequately resolve high-LET IR-induced DSBs. Current
      findings suggest that the functionality of the DNA-dependent protein kinase (DNA
      PK), comprised of the Ku70-Ku80 heterodimer and the DNA-PK catalytic subunit (DNA
      PKcs), is particularly perturbed by high-LET IR-induced clustered DSBs, rendering
      DNA-PK dependent NHEJ less relevant to resolving these lesions. By contrast, the
      NHEJ-associated DNA processing endonuclease Artemis shows a greater relevance to
      high-LET IR-induced DSB repair. Here, we will review the cellular response to
      high-LET irradiation, the implications of the chronic, low-dose modality of this
      exposure and molecular pathways that respond to high-LET irradiation induced
      DSBs, with particular emphasis on NHEJ factors. 

PMID- 24565813
TI  - Auditory processing and sensory behaviours in children with autism spectrum
      disorders as revealed by mismatch negativity.
AB  - Sensory dysfunctions may underlie key characteristics in children with Autism
      Spectrum Disorders (ASD). The current study aimed to investigate auditory change
      detection in children with ASD in order to determine event-related potentials to
      meaningless and meaningful speech stimuli. 11 high functioning boys with a
      diagnosis of autism spectrum disorders (mean age=13.0; SD=1.08) and 11 typically
      developing boys (mean age=13.7; SD=1.5) participated in a mismatch negativity
      (MMN) paradigm. Results revealed that compared to TD controls, the children with
      ASD showed significantly reduced MMN responses to both words and pseudowords in
      the frontal regions of the brain and also a significant reduction in their
      activation for words in the Central Parietal regions. In order to test the
      relationship between sensory processing and auditory processing, children
      completed the Adult and Adolescent Sensory Profile. As predicted, the children
      with ASD showed more extreme sensory behaviours and were significantly higher
      than their typically developing controls across three of the sensory quadrants
      (sensory sensitivity, low registration and sensory avoidance). Importantly, only
      auditory sensory sensitivity was able to account for the differences displayed
      for words in the frontal and central parietal regions when controlling for the
      effect of group, revealing an inverse relationship of the higher sensory
      sensitivity scores the less activation in response for words. We discuss how the
      expression of sensory behaviours in ASD may result in deficient
      neurophysiological mechanisms underlying automatic language processing. 

PMID- 24565814
TI  - The clinical utility of the auditory P300 latency subcomponent event-related
      potential in preclinical diagnosis of patients with mild cognitive impairment and
      Alzheimer's disease.
AB  - The present meta-analysis investigated the clinical utility of the auditory P300
      latency event-related potential in differentiating patients with Alzheimer's
      disease (AD), patients with mild cognitive impairment (MCI), and unaffected
      controls. Effect size estimates were computed from mean P300 latency measurements
      at midline electrodes between patients and unaffected controls using the random
      effects restricted maximum likelihood model. The effects of clinical and ERP/EEG
      methological variables were assessed in a moderator analysis. P300 latency was
      found to be significantly prolonged in patients with AD (and MCI) compared to
      unaffected controls. Shortened P300 latencies were observed when comparing
      patients with MCI to patients with AD. Clinically relevant differences in P300
      latency effect sizes were associated with mean age, interstimulus interval,
      stimulus difference, target frequency, reference electrode, and sampling rate.
      The meta-analytic findings provide robust statistical evidence for the use of the
      auditory P300 latency subcomponent as a biological marker of prodromal AD. 

PMID- 24565816
TI  - High-intensity exercise training for the prevention of type 2 diabetes mellitus.
AB  - Aerobic exercise training and diet are recommended for the primary prevention of
      type 2 diabetes mellitus and cardiovascular disease. The American Diabetes
      Association (ADA) recommends that adults with prediabetes engage in >= 150
      minutes per week of moderate activity and target a 7% weight loss. However,
      traditional moderate-intensity (MI) exercise training programs are often
      difficult to sustain for prediabetic adults; a commonly cited barrier to physical
      activity in this population is the "lack of time" to exercise. When matched for
      total energy expenditure, high-intensity (HI) exercise training has a lower
      overall time commitment compared with traditional low-intensity (LI) or MI
      exercise training. Several recent studies comparing HI exercise training with LI
      and MI exercise training reported that HI exercise training improves skeletal
      muscle metabolic control and cardiovascular function in a comparable and/or
      superior way relative to LI and MI exercise training. Although patients can
      accrue all exercise benefits by performing LI or MI activities such as walking,
      HI activities represent a time-efficient alternative to meeting physical activity
      guidelines. High-intensity exercise training is a potent tool for improving
      cardiometabolic risk for prediabetic patients with limited time and may be
      prescribed when appropriate. 

PMID- 24565817
TI  - Exercising with peripheral or autonomic neuropathy: what health care providers
      and diabetic patients need to know.
AB  - Both peripheral and autonomic neuropathies are characterized by a progressive
      loss of nerve fiber function. Most peripheral neuropathy affects the extremities,
      particularly the lower legs and the feet, but also the hands, whereas damage to
      the autonomic nervous system may lead to imbalances between the sympathetic and
      parasympathetic nerve fibers that innervate the heart and blood vessels, as well
      as abnormalities in heart rate control and vascular dynamics. To prescribe or
      engage in exercise that is both safe and effective, health care providers and
      patients with diabetes mellitus need to increase their understanding of the
      pathophysiological nature of neuropathies and the physical activity hurdles that
      may arise from the presence of a neuropathy. With proper care and preventative
      measures, patients with diabetes mellitus that experience either type of
      neuropathy can benefit from regular participation in mild to moderate aerobic,
      resistance, and balance activities, assuming they take any potential alterations
      into account to ensure that exercise is safe and effective. 

PMID- 24565818
TI  - Monitoring capabilities of the Omron HJ-720ITC pedometer.
AB  - PURPOSE: The purpose of our study was to examine the monitoring capabilities of
      the Omron HJ-720ITC pedometer and determine the feasibility of using it in
      physical activity interventions. METHODS: Using data from an 8-week lifestyle
      intervention study, we tested the capabilities of the pedometer for recording
      physical activity data. Data from a total of 28 subjects were used in our
      analysis. The total number of patient steps per day was recorded over the
      duration of an intervention, as well as "aerobic steps per day" (ie, those taken
      at a cadence of > 60 steps per minute for >= 10 consecutive minutes). Daily wear
      time was computed in order to ascertain participant compliance in wearing the
      pedometer. In addition, aerobic steps per minute were computed, providing an
      assessment of activity intensity during continuous walking bouts. RESULTS: Total
      steps per day and aerobic steps per day increased from baseline assessment to
      Week 8. Participants exceeded 100 steps/minute for 89% of their aerobic minutes,
      suggesting that they were in the moderate-intensity range (3-6 metabolic
      equivalent tasks) when performing continuous bouts of walking (> 10 minutes).
      CONCLUSION: The new pedometer is a reasonably priced, wearable activity monitor
      that is feasible for use in clinical and research settings.

PMID- 24565819
TI  - Barefoot versus shoe running: from the past to the present.
AB  - INTRODUCTION: Barefoot running is not a new concept, but relatively few people
      choose to engage in barefoot running on a regular basis. Despite the
      technological developments in modern running footwear, as many as 79% of runners
      are injured every year. Although benefits of barefoot running have been proposed,
      there are also potential risks associated with it. OBJECTIVE: To review the
      evidence-based literature concerning barefoot/minimal footwear running and the
      implications for the practicing physician. MATERIALS AND METHODS: Multiple
      publications were reviewed using an electronic search of databases such as
      Medline, Cinahl, Embase, PubMed, and Cochrane Database from inception until
      August 30, 2013 using the search terms barefoot running, barefoot running
      biomechanics, and shoe vs. barefoot running. RESULTS: Ninety-six relevant
      articles were found. Most were reviews of biomechanical and kinematic studies.
      ANALYSIS: There are notable differences in gait and other parameters between
      barefoot running and shoe running. Based on these findings and much anecdotal
      evidence, one could conclude that barefoot runners should have fewer injuries,
      better performance, or both. Several athletic shoe companies have designed
      running shoes that attempt to mimic the barefoot condition, and thus garner the
      purported benefits of barefoot running. CONCLUSION: Although there is no evidence
      that confirms or refutes improved performance and reduced injuries in barefoot
      runners, many of the claimed disadvantages to barefoot running are not supported
      by the literature. Nonetheless, it seems that barefoot running may be an
      acceptable training method for athletes and coaches, as it may minimize the risks
      of injury.

PMID- 24565820
TI  - Cast-saw injuries: assessing blade-to-skin contact during cast removal. Does
      experience or education matter?
AB  - BACKGROUND: Cast-saw injuries are sustained during cast removal or splitting of a
      cast when a hot cast-saw blade touches the patient's skin inadvertently during
      cast removal. Other studies have evaluated risk factors associated with saw-blade
      temperature, however, none have documented the number and duration of blade-to
      skin contacts during cast removal. METHODS: Using a pediatric long-arm model
      capable of detecting cast-saw blade contact, we tested the ability of health care
      providers to apply and remove casts before and after a brief education module.
      The total number and duration of "touches" between the saw and the model's "skin"
      were recorded. Correlations between user "touches," and experience and
      comparisons between pre- and post-education "touches" were performed. RESULTS: Of
      the 18 study participants, 16 touched the model surface with the cast saw; 7 of
      the 18 participants maintained blade contact with the skin for > 1 second 22
      times during the testing process. Participants with less experience averaged 20
      (+/- 16) touches, whereas more experienced participants averaged 24 (+/- 19)
      touches (P = 0.7). Average number of touches was similar-before 22 (+/- 20) and
      after 25 (+/- 22); P = 0.5-participants completed an education module. No
      correlation between experience or participation in the education program was
      found with decreased number of blade-to-skin touches. CONCLUSION: Nearly all
      clinicians inadvertently contacted the underlying skin with the cast-saw blade.
      In our limited sample size, experience and education did not prevent this;
      therefore, minimizing time of contact and blade temperature may be more important
      factors in minimizing cast-saw injuries.

PMID- 24565821
TI  - Increased prevalence of atrial fibrillation in the endurance athlete: potential
      mechanisms and sport specificity.
AB  - Atrial fibrillation is a common, often symptomatic, and concerning arrhythmia
      that can lead to heart failure, decreased athletic tolerance, and thromboembolic
      events; it has also been associated with increased mortality. Although atrial
      fibrillation is an uncommon condition in younger and otherwise healthy people,
      recent emerging evidence indicates that endurance athletes may be at particularly
      high risk of developing atrial fibrillation. We review the evidence that atrial
      fibrillation is associated with intense endurance athletics and we also explore
      the mechanisms by which this may occur. Finally, we consider some of the options
      that are available to treat athletes who develop atrial fibrillation. 

PMID- 24565822
TI  - The approach to elbow pain in the pediatric and adolescent throwing athlete.
AB  - Elbow pain in pediatric throwing athletes can be very concerning and challenging
      to diagnose. Diagnosis involves determining whether the injury is chronic or
      acute in nature and the anatomical location of the pain. Physicians should be
      aware of the sport-specific forces that predispose athletes with immature
      skeletons to injury and should be familiar with the common presentations of these
      injuries. In order to narrow the diagnosis, physicians should gather a detailed
      history of how and when the pain occurred in addition to performing a thorough
      physical exam that includes tests, such as the modified milking maneuver and the
      moving valgus stress test. Appropriate imaging helps physicians to confirm the
      diagnosis and elucidates any associated pathology in patients. In most cases, the
      treatment given to patients is conservative and involves rest, ice, non-steroidal
      anti-inflammatory drugs for pain, and an appropriate physical therapy regimen
      with a progressive return to play when symptoms have resolved. When patients fail
      to respond to conservative treatment, surgical intervention may be needed.
      Knowing when to refer patients for orthopedic evaluation helps athletes return to
      play quickly and safely. 

PMID- 24565823
TI  - Changes in collegiate starting pitchers' range of motion after single game and
      season.
AB  - The relationship of changes in glenohumeral range of motion (ROM) in a pitcher's
      throwing shoulder to a single pitching episode is not well described, and the
      causes of such changes over a season are controversial. We hypothesized that in
      pitchers for a collegiate baseball team, external rotation (ER) would increase,
      internal rotation (IR) would decrease, total ROM would be maintained, and the
      glenohumeral IR deficit would worsen in starting pitchers' shoulders after single
      pitching episodes and after the season. Participants were 6 starting pitchers for
      all 25 home games from a Division III National Collegiate Athletic Association
      team during 1 regular spring season. One examiner measured glenohumeral ER, IR,
      and total ROM with the arm abducted 90 degrees  pregame before stretching or
      throwing and immediately postgame before shoulder icing. Bilateral measurements
      were obtained on supine pitchers via a long-arm goniometer and custom bubble
      inclinometer. Innings, pitch count, and types of pitches were recorded for
      possible associations with any glenohumeral motion changes. Paired t tests were
      used to compare dominant and nondominant glenohumeral differences in ROM
      (significance, P < 0.05). Compared with pregame values, single-start postgame
      glenohumeral ER significantly increased (7.9 degrees  +/- 2.2 degrees ), single
      start IR did not significantly change, and single-start total ROM significantly
      increased (7.4 degrees  +/- 3.4 degrees ). Compared with preseason values,
      postseason glenohumeral ER significantly increased (10.2 degrees  +/- 6.2 degrees
      ), IR significantly decreased (-17.8 degrees  +/- 6.7 degrees ), and total ROM
      significantly decreased (-7.7 degrees  +/- 5.2 degrees ). In the collegiate
      throwing shoulder, changes in ER and total ROM occurred after 1 episode of
      starting pitching, and changes in ER, IR, and total ROM occurred over the full
      season. There was no association between the ROM changes and innings pitched,
      pitch count, or types of pitches thrown. In conclusion, for collegiate pitchers,
      changes in glenohumeral ROM occur after single starts and over the season,
      suggesting that monitoring motion changes throughout the season may be
      beneficial. 

PMID- 24565824
TI  - A review of femoroacetabular impingement and hip arthroscopy in the athlete.
AB  - Femoroacetabular impingement (FAI) is increasingly recognized as a pathological
      condition of the hip in athletes. Although it is not always symptomatic, the bone
      structure leading to FAI and its associated pathology can result in significant
      pain and performance decline in athletes. Recognition of athletes with
      symptomatic FAI is of the utmost importance, as prompt treatment is necessary in
      order to maintain desired sports activity levels and preserve joint function.
      This review explores the recent evidence on the evaluation, recognition, and
      treatment of femoroacetabular impingement, and discusses conservative management,
      postoperative rehabilitation, and treatment in the pediatric and master athlete
      populations. 

PMID- 24565825
TI  - Exercise and ankle sprain injuries: a comprehensive review.
AB  - Ankle sprains are common in team sports and sports played on courts, and often
      result in structural and functional alterations that lead to a greater reinjury
      risk. Specific exercises are often used to promote neuromuscular improvements in
      the prevention and rehabilitation of ankle injuries. This literature review
      summarizes the neuromuscular characteristics of common ankle sprains and the
      effectiveness of exercise as an intervention for improving neuromuscular function
      and preventing reinjury. Our review found that appropriate exercise prescription
      can increase static and dynamic balance and decrease injury recurrence. In
      particular, the addition of dynamic activities in the exercise program can be
      beneficial because of the anticipatory postural adjustments identified as a key
      factor in the injury mechanism. 

PMID- 24565828
TI  - How we treat sickle hepatopathy and liver transplantation in adults.
AB  - Sickle cell disease (SCD) has evolved into a debilitating disorder with emerging
      end-organ damage. One of the organs affected is the liver, causing "sickle
      hepatopathy," an umbrella term for a variety of acute and chronic pathologies.
      Prevalence of liver dysfunction in SCD is unknown, with estimates of 10%.
      Dominant etiologies include gallstones, hepatic sequestration, viral hepatitis,
      and sickle cell intrahepatic cholestasis (SCIC). In addition, causes of liver
      disease outside SCD must be identified and managed. SCIC is an uncommon, severe
      subtype, with outcome of its acute form having vastly improved with exchange
      blood transfusion (EBT). In its chronic form, there is limited evidence for EBT
      programs as a therapeutic option. Liver transplantation may have a role in a
      subset of patients with minimal SCD-related other organ damage. In the
      transplantation setting, EBT is important to maintain a low hemoglobin S fraction
      peri- and posttransplantation. Liver dysfunction in SCD is likely to escalate as
      life span increases and patients incur incremental transfusional iron overload.
      Future work must concentrate on not only investigating the underlying
      pathogenesis, but also identifying in whom and when to intervene with the 2
      treatment modalities available: EBT and liver transplantation.

PMID- 24565826
TI  - Diagnosis and treatment of low back pain in the pediatric population.
AB  - Back pain in the pediatric population is a common complaint presenting to sports
      medicine clinics. There is a wide differential that should be considered,
      including mechanical, infectious, neoplastic, inflammatory, and amplified
      musculoskeletal pain. The history, pain quality, and examination are key
      components to help distinguish the etiologies of the pain and direct further
      evaluation. Laboratory investigations, including blood counts and inflammatory
      markers, can provide insight into the diagnosis. The HLA-B27 antigen can be
      helpful if a spondyloarthropathy is suspected. Imaging as clinically indicated
      typically begins with radiographs, and the use of MRI, CT, or bone scan can
      provide additional information. Proper diagnosis of back pain is important
      because prognosis and treatments are significantly different. We review the
      pertinent evaluation, differential diagnoses, and treatment of low back pain in
      the pediatric population. 

PMID- 24565827
TI  - Molecular mechanisms of neutrophil dysfunction in glycogen storage disease type
      Ib.
AB  - Glycogen storage disease type Ib (GSD-Ib) is an autosomal-recessive syndrome
      characterized by neutropenia and impaired glucose homeostasis resulting from a
      deficiency in the glucose-6-phosphate (G6P) transporter (G6PT). The underlying
      cause of GSD-Ib neutropenia is an enhanced neutrophil apoptosis, but patients
      also manifest neutrophil dysfunction of unknown etiology. Previously, we showed
      G6PT interacts with the enzyme glucose-6-phosphatase-beta (G6Pase-beta) to
      regulate the availability of G6P/glucose in neutrophils. A deficiency in G6Pase
      beta activity in neutrophils impairs both their energy homeostasis and function.
      We now show that G6PT-deficient neutrophils from GSD-Ib patients are similarly
      impaired. Their energy impairment is characterized by decreased glucose uptake
      and reduced levels of intracellular G6P, lactate, adenosine triphosphate, and
      reduced NAD phosphate, whereas functional impairment is reflected in reduced
      neutrophil respiratory burst, chemotaxis, and calcium mobilization. We further
      show that the mechanism of neutrophil dysfunction in GSD-Ib arises from
      activation of the hypoxia-inducible factor-1alpha/peroxisome-proliferators
      activated receptor-gamma pathway. 

PMID- 24565829
TI  - Renal morphology in cats with diabetes mellitus.
AB  - In humans, diabetes mellitus (DM) is an important cause of renal damage, with
      glomerular lesions being predominant. In cats, although diabetes is a common
      endocrinopathy, it is yet unknown whether it leads to renal damage. The aim of
      the study was to compare renal histologic features and parameters of renal
      function in diabetic cats against a control population matched for age, gender,
      breed, and body weight. Thirty-two diabetic and 20 control cats were included.
      Kidney sections from paraffin-embedded kidney samples were stained and examined
      with optical microscopy to identify glomerular, tubulointerstitial, and vascular
      lesions and to assess their frequency and severity. Serum creatinine and urea
      concentrations were also compared. Glomerular lesions were observed in 29 cats
      overall, with mesangial matrix increase being more common (19 cats).
      Tubulointerstitial lesions were observed in 42 cats, including lymphocytic
      infiltration (29), fibrosis (22), or tubular necrosis (21). Vascular lesions were
      observed in 5 cases. The frequency and severity of histologic lesions did not
      differ between diabetic and control cats; however, among diabetics, those that
      survived longer after diagnosis had more glomerular and vascular lesions. Serum
      creatinine and urea concentrations were similar between groups; in diabetic cats
      median creatinine was 109 MUmol/l (range, 51-1200) and urea was 12 mmol/l (range,
      4-63), and in controls creatinine was 126 MUmol/l (range, 50-875) and urea 11
      mmol/l (range, 3-80). The results suggest that DM in cats does not lead to
      microscopically detectable kidney lesions or clinically relevant renal
      dysfunction. The authors hypothesize that the short life expectancy of diabetic
      cats may be the main reason for the difference from human diabetics. 

PMID- 24565830
TI  - Cellular sources of tenascin-C in canine mammary carcinomas.
AB  - Tenascin-C (Tn-C) is an extracellular matrix glycoprotein implicated in the
      progression of several human cancers. In canine mammary carcinomas, accumulation
      of Tn-C has been recognized in 3 different areas: regions of proliferating
      myoepithelial cells in complex carcinoma, basement membrane zone in low-grade
      simple carcinoma, and reactive stroma in high-grade simple carcinoma. To identify
      the Tn-C synthesizing cells in these areas, we utilized double-labeling
      immunohistochemistry, branched DNA in situ hybridization, and in situ
      hybridization-immunohistochemistry double-labeling techniques. In complex
      carcinomas, Tn-C was generated by proliferating myoepithelial cells. Tn-C in low
      grade simple carcinomas was also derived from myoepithelial cells existing as a
      basal monolayer. However, stromal Tn-C in high-grade carcinomas was mainly
      synthesized by fibroblasts/myofibroblasts, similar to human breast cancer. Thus,
      the origin of Tn-C in canine mammary carcinomas differs between low- and high
      grade malignancies. The role of myoepithelial cell-generated Tn-C is not yet
      understood. 

PMID- 24565831
TI  - Bone speed of sound throughout lifetime assessed with quantitative ultrasound in
      a Mexican population.
AB  - The purpose of this study was to assess the bone speed of sound (SoS) through
      lifetime of a large Mexican population sample by determining the SoS from the
      radius and tibia using quantitative ultrasound (QUS). This is a cross-sectional
      evaluation of participants in the Mexican Health Workers Cohort Study. QUS
      measurements were performed using Sunlight Omnisense 8000P; Z- and T-scores were
      calculated for both sexes at the distal third of the radius and midshaft tibia,
      both on the nondominant side. A locally weighted regression smoothing scatterplot
      model was used to identify different phases of bone accretion and loss. A total
      of 9128 participants aged 1-75 yr were measured with QUS. Bone SoS accretion
      began 5 yr earlier in girls than boys (p<0.05). Maximal SoS or peak bone SoS was
      noted at 28 yr in the radius and at 22 yr in the tibia. Postmenopausal women (45
      50 yr) showed significant SOS decrease at both sites (p<0.05) compared with men.
      Using the locally weighted regression smoothing scatterplot model, we found 5
      different phases that constitute the biological development of bone over the life
      course, from ages 1-6, 7-12, 12-25, 25-50, and 50-75 yr (p<0.05). Our study shows
      the age- and sex-dependent changes and different phases of bone development
      expressed by SoS measurements of the radius and tibia. The values reported in
      this study can be used as a reference for urban Mexican population.

PMID- 24565832
TI  - Evaluation of the potential of antipsychotic agents to induce catalepsy in rats:
      assessment of a new, commercially available, semi-automated instrument.
AB  - Haloperidol induced catalepsy was determined using the classic bar test and a new
      MED Associates Catalepsy Test Chamber instrument. The dose that produced an
      adverse effect in 50% of rats (AED50) for haloperidol was calculated using the
      instrument data as 0.29 mg/kg. Hand scoring of the video recordings gave AED50
      values of 0.30 and 0.31 mg/kg, both well within the 95% CL of the instrument
      data. Clozapine was also evaluated and catalepsy was not detected up to 40 mg/kg.
      No significant difference was found between the instrument and hand scoring data.
      The instrument was useful for testing haloperidol and clozapine, relieving much
      of the tedium and variability experienced without its use. It was especially
      valuable at measuring shorter time periods, where the researcher cannot react as
      quickly. Finally, olanzapine was also evaluated. However, clenched forepaws and
      hind paws prevented the use of the instrument alone at higher doses. A backup
      stopwatch was used for the bar test in these cases. Some of the advantages and
      limitations are discussed. Results are also compared to the crossed-legs position
      (CLP) test for all three antipsychotics. While haloperidol gave similar results
      at all concentrations tested, clozapine deviated significantly at the highest
      dose (40 mg/kg) displaying catalepsy in the CLP test but not in the bar test.
      Olanzapine displayed catalepsy in rats significantly different from vehicle at 40
      mg/kg in both the bar and CLP tests. However, the CLP test may be more suited to
      compounds with gripping problems which prevent the consistent grasping of the
      bar. Overall, the instrument was found to be a useful aid in conducting the bar
      test for catalepsy. The CLP test was found to complement the bar test under
      certain conditions and could provide additional data that might be missed by the
      bar test for compounds producing grasping problems.

PMID- 24565833
TI  - Selection against glycosylation sites in potential target proteins of the general
      HMWC N-glycosyltransferase in Haemophilus influenzae.
AB  - The HMWABC system of non-typeable Haemophilus influenzae (NTHi) encodes the HMWA
      adhesin glycoprotein, which is glycosylated by the HMWC glycosyltransferase. HMWC
      is a cytoplasmic N-glycosyltransferase, homologues of which are widespread in the
      Pasteurellaceae. We developed an assay for nonbiased detection of glycoproteins
      in NTHi based on metabolic engineering of the Leloir pathway and growth in media
      containing radiolabelled monosaccharides. The only glycoprotein identified in
      NTHi by this assay was HMWA. However, glycoproteomic analyses ex vivo in
      Escherichia coli showed that HMWC of NTHi was a general glycosyltransferase
      capable of glycosylating selected asparagines in proteins other than its HMWA
      substrate, including Asn78 in E. coli 30S ribosomal protein S5. The equivalent
      residue in S5 homologues in H. influenzae or other sequenced Pasteurellaceae
      genomes is not asparagine, and these organisms also showed significantly fewer
      than expected potential sites of glycosylation in general. Expression of active
      HMWC in E. coli resulted in growth inhibition compared with expression of
      inactive enzyme, consistent with glycosylation by HMWC detrimentally affecting
      the function of some E. coli proteins. Together, this supports the presence of a
      selective pressure in the Pasteurellaceae against glycosylation sites that would
      be modified by the general N-glycosyltransferase activity of HMWC. 

PMID- 24565834
TI  - Modulation of endoplasmic reticulum (ER) stress-induced autophagy by C/EBP
      homologous protein (CHOP) and inositol-requiring enzyme 1alpha (IRE1alpha) in
      human colon cancer cells.
AB  - To explore the relationship between UPR and autophagy in intestinal epithelial
      cells, we investigated whether autophagy was induced by endoplasmic reticulum
      (ER) stress in colon cancer cell lines. We demonstrated that autophagy was
      induced by ER stress in HT29, SW480, and Caco-2 cells. In these cells, inositol
      requiring enzyme1alpha (IRE1alpha) and C/EBP homologous protein (CHOP) were
      involved in the ER stress-autophagy pathway, and CHOP was a regulator of
      IRE1alpha protein expression. Our findings suggest that CHOP promotes IRE1alpha
      and autophagy especially in ER stress conditions. This study will provide
      important insights into the disclosure of the ER stress-autophagy pathway. 

PMID- 24565835
TI  - Zinc protects cyclophosphamide-induced testicular damage in rat: involvement of
      metallothionein, tesmin and Nrf2.
AB  - The role of zinc (Zn) in the protection of germ cells against testicular
      toxicants has long been elucidated, but the exact molecular mechanisms have not
      yet been explored. Cyclophosphamide (CP), one of the most commonly used
      anticancer drugs survived ages of treatment, but the unwanted toxicity limits its
      clinical usage. The present investigation was aimed to explore the role of Zn and
      its associated pathways in CP-induced testicular toxicity in S.D. rat. CP was
      administered in saline 30 mg/kg 5* weekly for 3 weeks (total dose of 450 mg/kg)
      by i.p. route, while Zn was supplemented by oral route at the doses of 1, 3,
      10mg/kg/day for 3 weeks. CP significantly reduced Zn levels in serum and testes,
      body and testicular weight, sperm count and motility, spermiogenic cells, plasma
      testosterone and significantly increased the oxidative stress, sperm head
      abnormalities, sperm DNA damage with decreased chromatin and acrosome integrity;
      while Zn supplementation ameliorated the same. The present results demonstrated
      that Zn supplementation protected against CP-induced testicular damages by
      modulating metallothionein (MT), tesmin and Nrf2 associated pathways. Thus Zn
      supplementation during anticancer therapy might be potentially beneficial in
      reducing the off target effects associated with oxidative stress.

PMID- 24565836
TI  - Pax3 function is required specifically for inner ear structures with melanogenic
      fates.
AB  - Pax3 mutations result in malformed inner ears in Splotch mutant mice and hearing
      loss in humans with Waardenburg's syndrome type I. In the inner ear, Pax3 is
      thought to be involved mainly in the development of neural crest. However, recent
      studies have shown that Pax3-expressing cells contribute extensively to multiple
      inner ear structures, some of which were considered to be derived from the otic
      epithelium. To examine the specific functions of Pax3 during inner ear
      development, fate mapping of Pax3 lineage was performed in the presence or
      absence of functional Pax3 proteins using Pax3(Cre) knock-in mice bred to Rosa26
      reporter (R26R) line. beta-gal-positive cells were widely distributed in
      Pax3(Cre/+); R26R inner ears at embryonic day (E) 15.5, including the
      endolymphatic duct, common crus, cristae, maculae, cochleovestibular ganglion,
      and stria vascularis. In the absence of Pax3 in Pax3(Cre/Cre); R26R inner ears,
      beta-gal-positive cells disappeared from regions with melanocytes such as the
      stria vascularis of the cochlea and dark cells in the vestibule. Consistently,
      the expression of Dct, a melanoblast marker, was also absent in the mutant inner
      ears. However, when examined at E11.5, beta-gal positive cells were present in
      Pax3(Cre/Cre) mutant otocysts, whereas Dct expression was absent, suggesting that
      Pax3 lineage with a melanogenic fate migrated to the inner ear, yet failed to
      differentiate and survive without Pax3 function. Gross inner ear morphology was
      generally normal in Pax3(Cre/Cre) mutants, unless neural tube defects extended to
      the cranial region. Taken together, these results suggest that despite the
      extensive contribution of Pax3-expressing cells to multiple inner ear tissues,
      Pax3 function is required specifically for inner ear components with melanogenic
      fates. 

PMID- 24565837
TI  - Saikosaponin C inhibits lipopolysaccharide-induced apoptosis by suppressing
      caspase-3 activation and subsequent degradation of focal adhesion kinase in human
      umbilical vein endothelial cells.
AB  - Bacterial lipopolysaccharide (LPS) is an important mediator of inflammation and a
      potent inducer of endothelial cell damage and apoptosis. In this study, we
      investigated the protective effects of saikosaponin C (SSc), one of the active
      ingredients produced by the traditional Chinese herb, Radix Bupleuri, against LPS
      induced apoptosis in human umbilical endothelial cells (HUVECs). LPS triggered
      caspase-3 activation, which was found to be important in LPS-induced HUVEC
      apoptosis. Inhibition of caspase-3 also inhibited LPS-induced degradation of
      focal adhesion kinase (FAK), indicating that caspase-3 is important in LPS
      mediated FAK degradation as well as in apoptosis in HUVECs. SSc significantly
      inhibited LPS-induced apoptotic cell death in HUVECs through the selective
      suppression of caspase-3. SSc was also shown to rescue LPS-induced FAK
      degradation and other cell adhesion signals. Furthermore, the protective effects
      of SSc against LPS-induced apoptosis were abolished upon pretreatment with a FAK
      inhibitor, highlighting the importance of FAK in SSc activity. Taken together,
      these results show that SSc efficiently inhibited LPS-induced apoptotic cell
      death via inhibition of caspase-3 activation and caspase-3-mediated-FAK
      degradation. Therefore, SSc represents a promising therapeutic candidate for the
      treatment of vascular endothelial cell injury and cellular dysfunction. 

PMID- 24565838
TI  - SAW1 is required for SDSA double-strand break repair in S. cerevisiae.
AB  - SAW1, coding for Saw1, is required for single-strand annealing (SSA) DNA double
      strand break (DSB) repair in Saccharomycescerevisiae. Saw1 physically associates
      with Rad1 and Rad52 and recruits the Rad1-Rad10 endonuclease. Herein we show by
      fluorescence microscopy that SAW1 is similarly required for recruitment of Rad10
      to sites of Synthesis-Dependent Strand Annealing (SDSA) and associates with sites
      of SDSA repair in a manner temporally overlapped with Rad10. The magnitude of
      induction of colocalized Saw1-CFP/Rad10-YFP/DSB-RFP foci in SDSA is more dramatic
      in S and G2 phase cells than in M phase, consistent with the known mechanism of
      SDSA. We observed a substantial fraction of foci in which Rad10 was localized to
      the repair site without Saw1, but few DSB sites that contained Saw1 without
      Rad10. Together these data are consistent with a model in which Saw1 recruits
      Rad1-Rad10 to SDSA sites, possibly even binding as a protein-protein complex, but
      departs the repair site in advance of Rad1-Rad10. 

PMID- 24565839
TI  - p53 down-regulates SETDB1 gene expression during paclitaxel induced-cell death.
AB  - Paclitaxel (PTX) is a chemotherapeutic drug which induces tubulin stability and
      regulates expression of death related genes in human cancer cells. Its anticancer
      mechanism is well known, however its effects on chromatin remodeling factors are
      poorly understood. In this study, we examine if PTX affects expression of SETDB1
      HMTase during cell death. PTX induces cell death via G2/M arrest in human lung
      cancer cells. PTX treatment induces the p53 protein, but down-regulates
      expression of SETDB1 at the transcriptional level as well as the protein level.
      SETDB1 promoter activity is increased to approximately 30-fold in normal
      condition, but the activity is significantly inhibited in the PTX treated group.
      In addition, p53 transfection inhibits SETDB1 promoter activity. The p53 protein
      directly binds to proximal region of the SETDB1 promoter, and H3K9me3 occupancy
      in this region also increased in the presence of p53. Immunoprecipitation
      experiment showed interaction of p53 and SUV39H1, suggesting that association of
      p53 and SUV39H1 is responsible for increased H3K9me3 occupancy and transcription
      repression of SETDB1. This result demonstrates that PTX down-regulates SETDB1
      gene expression in a p53 dependent manner, and p53 might participate in
      heterochromatic repression on the promoter regions of SETDB1. 

PMID- 24565840
TI  - Effects of miR-31 on the osteogenesis of human mesenchymal stem cells.
AB  - Exploring the molecular mechanisms that regulate the osteogenesis of human
      mesenchymal stem cells (hMSCs) will bring us more efficient methods for improving
      the treatment of bone-related diseases. In this study, we analyzed the effects of
      miR-31 on the osteogenesis of hMSCs. The overexpression of miR-31 repressed the
      osteogenesis of hMSCs, whereas the downregulation enhanced this process. SATB2
      was testified to be a direct target of miR-31, and its effects on the
      osteogenesis were also described. Most importantly, the knockdown of SATB2
      attenuated miR-31's osteogenic effects. Taken together, our findings suggest that
      miR-31 regulates the osteogenesis of hMSCs by targeting SATB2. 

PMID- 24565841
TI  - Activation of matrix metalloproteinase-26 by HOXA10 promotes embryo adhesion in
      vitro.
AB  - Successful embryonic implantation requires an effective maternal-embryonic
      molecular dialogue. However, the detailed mechanisms of epithelial-embryo
      adhesion remain poorly understood. Here, we report that matrix metalloproteinase
      26 (MMP-26) is a novel downstream target gene of homeobox a 10 (HOXA10) in human
      endometrial cells. HOXA10 binds directly to a conserved TTAT unit (-442 to -439)
      located within the 5' regulatory region of the MMP-26 gene and regulates the
      expression and secretion of MMP-26 in a concentration-dependent manner. Moreover,
      the adenovirus-mediated overexpression of MMP-26 in Ishikawa cells markedly
      increased BeWo spheroid adhesion. An antibody blocking assay further demonstrated
      that the promotion of BeWo spheroid adhesion by HOXA10 and MMP-26 was
      significantly inhibited by pre-treatment with a specific antibody against MMP-26.
      These results demonstrate that the HOXA10-mediated expression of MMP-26 promotes
      embryo adhesion during the process of embryonic implantation. 

PMID- 24565842
TI  - Fibroblast growth factor receptor 4 promotes progression and correlates to poor
      prognosis in cholangiocarcinoma.
AB  - Fibroblast growth factor receptor 4 (FGFR4) is related to poor prognosis of
      several cancers, but the correlation between FGFR4 expression and
      cholangiocarcinoma (CCA) has not been well elucidated. We investigated the
      expression of FGFR4 in 83 intrahepatic cholangiocarcinomas (IHCCs), 75 perihilar
      cholangiocarcinomas (PHCCs) and 41 distal cholangiocarcinomas (DCCs) by
      immunohistochemistry (IHC), and subsequently evaluated association of FGFR4 with
      clinicopathologic parameters and survival rate. The rate of FGFR4 higher
      expression was 61.4% (51/83) in IHCCs, 53.3% (40/75) in PHCCs and 56.1% (23/41)
      in DCCs. FGFR4 expression was significantly related to poor prognosis of IHCC
      (P=0.002) and PHCC (P=0.019) with univariate analysis, and also identified as an
      independent prognostic factor in IHCC (P=0.045) and PHCC (P=0.049) with
      multivariate analysis. Additionally, with functional assays in vitro, we found
      FGFR4 can induce proliferation, invasion and epithelial-mesenchymal transition
      (EMT) of CCA cell lines with FGF19 stimulation. Moreover, FGFR4 inhibitor AP24354
      can suppress proliferation, invasion and induce apoptosis of CCA cells. In
      conclusion, FGFR4 expression can be identified as a significant independent
      prognostic biomarker of IHCC and PHCC. FGFR4 played a pivotal role in
      proliferation, invasion and EMT of CCA. FGFR4 inhibitor can suppress
      proliferation, invasion and induce apoptosis of CCA, indicating that FGFR4 may
      act as a potential therapeutic target. 

PMID- 24565843
TI  - Activation of alpha adrenergic and muscarinic receptors modifies early glucose
      suppression of cytoplasmic Ca(2+) in pancreatic beta-cells.
AB  - Elevation of glucose induces transient inhibition of insulin release by lowering
      cytoplasmic Ca(2+) ([Ca(2+)]i) below baseline in pancreatic beta-cells. The
      period of [Ca(2+)]i decrease (phase 0) coincides with increased glucagon release
      and is therefore the starting point for antisynchronous pulses of insulin and
      glucagon. We now examine if activation of adrenergic alpha2A and muscarinic M3
      receptors affects the initial [Ca(2+)]i response to increase of glucose from 3 to
      20mM in beta-cells situated in mouse islets. In the absence of receptor
      stimulation the elevation of glucose lowered [Ca(2+)]i during 90-120 s followed
      by rise due to opening of voltage-dependent Ca(2+) channels. The period of
      [Ca(2+)]i decrease was prolonged by activation of the alpha2A adrenergic
      receptors (1 MUM epinephrine or 100 nM clonidine) and shortened by stimulation of
      the muscarinic M3 receptors (0.1 MUM acetylcholine). The latter effect was
      mimicked by the Na/K pump inhibitor ouabain (10-100 MUM). The results indicate
      that prolonged initial decrease (phase 0) is followed by slow [Ca(2+)]i rise and
      shorter decrease followed by fast rise. It is concluded that the period of
      initial decrease of [Ca(2+)]i regulates the subsequent beta-cell response to
      glucose.

PMID- 24565844
TI  - Inhibitory effect of p53 on mitochondrial content and function during
      adipogenesis.
AB  - The p53 protein is known as a guardian of the genome and is involved in energy
      metabolism. Since the metabolic system is uniquely regulated in each tissue, we
      have anticipated that p53 also would play differential roles in each tissue. In
      this study, we focused on the functions of p53 in white adipose tissue
      (adipocytes) and skeletal muscle (myotubes), which are important peripheral
      tissues involved in energy metabolism. We found that in 3T3-L1 preadipocytes, but
      not in C2C12 myoblasts, p53 stabilization or overexpression downregulates the
      expression of Ppargc1a, a master regulator of mitochondrial biogenesis. Next, by
      using p53-knockdown C2C12 myotubes or 3T3-L1 preadipocytes, we further examined
      the relationship between p53 and mitochondrial regulation. In C2C12 myoblasts,
      p53 knockdown did not significantly affect Ppargc1a expression and mtDNA, but did
      suppress differentiation to myotubes, as previously reported. However, in 3T3-L1
      preadipocytes and mouse embryonic fibroblasts, p53 downregulation enhanced both
      differentiation into adipocytes and mitochondrial DNA content. Furthermore, p53
      depleted 3T3-L1 cells showed increase in mitochondrial proteins and enhancement
      of both Citrate Synthase and Complex IV activities during adipogenesis. These
      results show that p53 differentially regulates cell differentiation and
      mitochondrial biogenesis between adipocytes and myotubes, and provide evidence
      that p53 is an inhibitory factor of mitochondrial regulation in adipocyte
      lineage. 

PMID- 24565845
TI  - The progression of comorbidity in IL-18 transgenic chronic obstructive pulmonary
      disease mice model.
AB  - Patients with severe COPD are known to have comorbidities such as emaciation, cor
      pulmonale and right heart failure, muscle weakness, hyperlipemia, diabetes
      mellitus, osteoporosis, muscle atrophy, arterial sclerosis, hypertension, and
      depression. Therefore, treatment for COPD needs to focus on these comorbidities
      as well as the lungs. We previously reported a new mouse model of COPD utilizing
      the human surfactant protein C promoter SP-C to drive the expression of mature
      mouse IL-18 cDNA; constitutive IL-18 overproduction in the lungs of transgenic
      (Tg) mice induces severe emphysematous change, dilatation of the right ventricle,
      and mild pulmonary hypertension with aging. In the present study, we evaluated
      the progression of comorbidity in our COPD model. In female Tg mice, significant
      weight loss was observed at 16 weeks and beyond, when compared with control wild
      type (WT) mice. This weight loss was suppressed in IL-13-deficient (knockout; KO)
      Tg mice. Muscle weight and bone mineral density were significantly decreased in
      aged Tg mice relative to control WT and IL-13 KO Tg mice. The aged Tg mice also
      showed impaired glucose tolerance. IL-18 and IL-13 may play important roles in
      the pathogenesis of comorbidity in COPD patients.

PMID- 24565846
TI  - TCP10L acts as a tumor suppressor by inhibiting cell proliferation in
      hepatocellular carcinoma.
AB  - TCP10L (T-complex 10 (mouse)-like) has been identified as a liver and testis
      specific gene. Although a potential transcriptional suppression function of
      TCP10L has been reported previously, biological function of this gene still
      remains largely elusive. In this study, we reported for the first time that
      TCP10L was significantly down-regulated in clinical hepatocellular carcinoma
      (HCC) samples when compared to the corresponding non-tumorous liver tissues.
      Furthermore, TCP10L expression was highly correlated with advanced cases
      exceeding the Milan criteria. Overexpression of TCP10L in HCC cells suppressed
      colony formation, inhibited cell cycle progression through G0/G1 phase, and
      attenuated cell growth in vivo. Consistently, silencing of TCP10L promoted cell
      cycle progression and cell growth. Therefore, our study has revealed a novel
      suppressor role of TCP10L in HCC, by inhibiting proliferation of HCC cells, which
      may facilitate the diagnosis and molecular therapy in HCC. 

PMID- 24565848
TI  - Direct identification of mycobacteria from culture media using a multiplex real
      time PCR assay: report on its application in a clinical laboratory in a region of
      high tuberculosis endemicity.
AB  - There are few commercial assays that easily and correctly identify the
      mycobacteria from culture in a clinical laboratory with a high workload. Thus, we
      developed and evaluated a scheme for the identification of mycobacteria using a
      multiplex real-time PCR assay and report on its application in our laboratory.
      The scheme consisted of 3 stepwise PCRs. Mycobacterium tuberculosis complex (MTC)
      and nontuberculous mycobacteria (NTM) were differentially detected in the step 1
      PCR, and the NTM species were identified in the step 2 and 3 PCRs. Over the 1.5
      year study period, 1136 isolates of MTC and 618 isolates of NTM were detected,
      and the species of 608 (98.4%) of the 618 NTM isolates were identified. We
      conclude that the established scheme is a very useful diagnostic approach for the
      rapid and accurate identification of MTC and clinically relevant NTM in a
      clinical laboratory in a region where tuberculosis is endemic. 

PMID- 24565847
TI  - A novel exendin-4 human serum albumin fusion protein, E2HSA, with an extended
      half-life and good glucoregulatory effect in healthy rhesus monkeys.
AB  - Glucagon-like peptide-1 (GLP-1) has attracted considerable research interest in
      terms of the treatment of type 2 diabetes due to their multiple glucoregulatory
      functions. However, the short half-life, rapid inactivation by dipeptidyl
      peptidase-IV (DPP-IV) and excretion, limits the therapeutic potential of the
      native incretin hormone. Therefore, efforts are being made to develop the long
      acting incretin mimetics via modifying its structure. Here we report a novel
      recombinant exendin-4 human serum albumin fusion protein E2HSA with HSA molecule
      extends their circulatory half-life in vivo while still retaining exendin-4
      biological activity and therapeutic properties. In vitro comparisons of E2HSA and
      exendin-4 showed similar insulinotropic activity on rat pancreatic islets and GLP
      1R-dependent biological activity on RIN-m5F cells, although E2HSA was less potent
      than exendin-4. E2HSA had a terminal elimation half-life of approximate 54 h in
      healthy rhesus monkeys. Furthermore, E2HSA could reduce postprandial glucose
      excursion and control fasting glucose level, dose-dependent suppress food intake.
      Improvement in glucose-dependent insulin secretion and control serum glucose
      excursions were observed during hyperglycemic clamp test (18 h) and oral glucose
      tolerance test (42 h) respectively. Thus the improved physiological
      characterization of E2HSA make it a new potent anti-diabetic drug for type 2
      diabetes therapy.

PMID- 24565849
TI  - Reduction of linezolid-associated thrombocytopenia by the dose adjustment based
      on the risk factors such as basal platelet count and body weight.
AB  - The aim of the present study was to evaluate the efficacy of dose modification
      based on the risk factor for linezolid-induced thrombocytopenia. A multivariate
      logistic regression analysis performed in the observational study showed that low
      body weight of <55 kg (odds ratio [OR]: 33.2, 95% confidence interval [CI]: 2.16
      510.1, P = 0.012) and the baseline platelet count of <200 * 10(3)/mm(3) (OR:
      24.9, 95% CI: 1.53-404.7, P = 0.024) were found to be risk factors for linezolid
      induced thrombocytopenia. In the subsequent intervention study, in which daily
      dose of linezolid was set to 20 mg/kg in patients with either one of the risk
      factors or 1200 mg in those without any risk factor, the onset of
      thrombocytopenia was significantly prolonged in the intervention study group (P =
      0.043), without reducing clinical efficacy. These findings suggest that dose
      adjustment of linezolid is effective in preventing thrombocytopenia without
      reducing its clinical efficacy in patients having risk factors. 

PMID- 24565850
TI  - Comparison of a conventional and nested PCR for diagnostic confirmation and
      genotyping of Orientia tsutsugamushi.
AB  - A nested polymerase chain reaction (PCR) targeting the 56-kDa antigen gene is
      currently the most commonly used molecular technique for confirmation of scrub
      typhus and genotyping of Orientia tsutsugamushi. In this study, we have compared
      the commonly used nested PCR (N-PCR) with a single-step conventional PCR (C-PCR)
      for amplification and genotyping. Eschar samples collected from 24 patients with
      scrub typhus confirmed by IgM enzyme-linked immunosorbent assay were used for DNA
      extraction following which amplifications were carried out using nested and C-PCR
      methods. The amplicons were sequenced and compared to other sequences in the
      database using BLAST. Conventional PCR showed a high positivity rate of 95.8%
      compared to the 75% observed using N-PCR. On sequence analysis, the N-PCR
      amplified region showed more variation among strains than the C-PCR amplified
      region. The C-PCR, which is more economical, provided faster and better results
      compared to N-PCR. 

PMID- 24565851
TI  - vanA-containing E. faecium isolates of clonal complex CC17 in clinical and
      environmental samples in a Tunisian hospital.
AB  - Twenty-eight vancomycin (VA)-resistant enterococci isolated from different
      patients (n = 16) and also from the environment (n = 12) were recovered in a
      Tunisian military hospital during 2012-2013. The mechanisms of resistance to VA
      and to other antibiotics as well as the presence of esp and hyl virulence genes
      were determined in these isolates by PCR, being their clonal relationship
      analyzed by pulsed-field gel electrophoresis (PFGE). VA resistance mechanisms
      detected were as follows (species-patient/environment): vanA (Enterococcus
      faecium, 13/5), vanC1 (Enterococcus gallinarum, 3/0), and vanC2 (Enterococcus
      casseliflavus, 0/7). Most of the VA-resistant enterococci presented a
      multiresistance phenotype and harbored different resistance genes (erm(B),
      tet(M), tet(L), ant(6)-Ia, aac(6')-aph(2"), aph(3')-IIIa, and catA). The PFGE
      revealed the presence of 3 clones (A, B, C) and 1 closely related pattern (A1)
      among the 13 vanA-containing E. faecium isolates of patients showing 11 of them
      the A-A1 patterns. The clone A was also detected in all 5 environmental vanA
      containing E. faecium isolates. Strains did not contain esp or hyl virulence
      genes. Multilocus sequence typing was performed in 4 E. faecium isolates
      representative of the 4 detected pulsotypes (A, A1, B, and C), and 2 different
      sequence types were identified (ST18 and ST80), both of them included in clonal
      complex CC17. These strains contained the IS16 element and showed ampicillin and
      ciprofloxacin resistance. VA resistance could be an emerging problem in Tunisia,
      and this is one of the first cases described so far in this country. 

PMID- 24565852
TI  - Mediator of RNA polymerase II transcription subunit 19 promotes osteosarcoma
      growth and metastasis and associates with prognosis.
AB  - Osteosarcoma (OS) is the most common primary malignant tumour of bone. Nearly 30
      40% of OS patients have a poor prognosis despite multimodal treatments. Because
      the carcinogenesis of OS remains unclear, the identification of new oncogenes
      that control the tumourigenesis and progression of OS is crucial for developing
      new therapies. Here, we found that the expression of Mediator of RNA polymerase
      II transcription subunit 19 (Med19) was increased in OS samples from patients
      compared to normal bone tissues. Cyclin D1 and cyclin B1 are upregulated in Med19
      positive OS tissues. Importantly, among 97 OS patients of Enneking stage IIB or
      IIIB, Med19 expression was correlated with metastasis (P<0.05) and poor prognosis
      (P<0.01). Med19 knockdown significantly induced growth inhibition, reduced colony
      forming ability and suppressed migration in the OS cell lines Saos-2 and U2OS,
      along with the downregulated expression of cyclin D1 and cyclin B1. Med19
      knockdown also induced apoptosis in Saos-2 cells via induction of caspase-3 and
      poly ADP-ribose polymerase (PARP). In addition, Med19 knockdown significantly
      suppressed tumour growth in an OS xenograft nude mouse model via suppression of
      cyclin D1 and cyclin B1. Simultaneously, Med19 downregulation decreased the
      expression of Ki67 and proliferating cell nuclear antigen (PCNA) in tumour
      samples from OS xenograft nude mice. Med19 depletion remarkably reduced tumour
      metastasis in a model of OS metastatic spreading. Taken together, our data
      suggest that Med19 acts as an oncogene in OS via a possible cyclin D1/cyclin B1
      modulation pathway. 

PMID- 24565853
TI  - Overexpression of CMET is associated with signal transducer and activator of
      transcription 3 activation and diminished prognosis in oesophageal adenocarcinoma
      but not in squamous cell carcinoma.
AB  - BACKGROUND: Inhibition of cMet is a promising therapeutic approach in human
      cancer, but few data in oesophageal cancer exist. METHODS: Expression of
      mesenchymal-epithelial transition factor (cMet), epidermal growth factor receptor
      (EGFR) and phosphatase and tensin homologue (PTEN) were investigated
      immunohistochemically in 246 oesophageal carcinomas (128 adenocarcinomas (AC);
      118 squamous cell carcinomas (SCC)) and corresponding metastases in a subset of
      AC (n=42). Data on phosphorylated signal transducer and activator of
      transcription 3 (pSTAT3) and HER2 expression and on lymphovascular invasion (LVI)
      of tumour cells were available from previous studies. RESULTS: Overexpression of
      cMet was seen in 44 (34.4%) of AC, and nine (7.6%) of SCC (p<0.001, Chi square
      test). In AC but not in SCC, cMet expression correlated with EGFR expression
      (p<0.001, Chi square test), pSTAT3 expression (p=0.01, Chi square tests) and LVI
      of tumour cells (p<0.001, Chi square test). Overexpression of cMet was associated
      with shorter disease free, disease specific and overall survival of AC patients
      (p<0.05, Cox regression, respectively). All cMet positive ACs in which metastases
      were investigated had also cMet positive lymph node and distant metastases, but
      25% of cMet negative primary tumours showed cMet positive lymph node and 33%
      distant metastases. CONCLUSIONS: CMet plays no relevant role in most oesophageal
      SCC. In contrast, cMet overexpression seems to be a key oncogene in about 35% of
      oesophageal AC, representing a highly promising therapeutic target and prognostic
      factor.

PMID- 24565854
TI  - Poor prognosis and advanced clinicopathological features of clear cell renal cell
      carcinoma (ccRCC) are associated with cytoplasmic subcellular localisation of
      Hypoxia inducible factor-2alpha.
AB  - BACKGROUND: Pre-clinical studies have implicated hypoxia inducible factor (HIF)
      2alpha as an important oncogene for clear cell renal cell carcinoma (ccRCC).
      Generally considered to act as a nuclear transcription factor, a recent study has
      also implicated HIF-2alpha as a protein translational initiation complex function
      within the cytoplasm (Uniacke et al., 2012). We hypothesised that both the
      absolute expression as well as the sub-cellular localisation of HIF-2alpha would
      predict clinicopathological features and cancer specific survival (CSS) in ccRCC.
      METHODS: A tissue microarray (TMA) study was conducted on three hundred and eight
      ccRCC patients. Survival differences were investigated with the log rank test and
      associations with CSS with uni- and multivariate Cox regression analyses.
      Recursive partition tree analysis was used to identify relevant cutoff values.
      RESULTS: High HIF-2alpha nuclear (N) (cutoff >32%) expression was associated with
      smaller tumour sizes (p=0.002) and lower Fuhrman grades (p=0.044), whereas
      tumours with high cytoplasmic (C) HIF-2alpha (>0%) more often had positive lymph
      nodes (p=0.004), distant metastases (p=0.021) and higher Fuhrman grades
      (p<0.0001). After adjustment for TNM stage, Eastern Cooperative Oncology Group
      performance status (ECOG PS), and Fuhrman grade, both continuous (p<0.0001) and
      dichotomised (p<0.0001) HIF-2alpha C variables remained significant predictors of
      CSS, while neither HIF-2alpha N variable was retained. CONCLUSION: Our
      investigation supports that HIF-2alpha may have a unique tumour promoter role in
      the cytoplasm. This preliminary finding justifies further experimental and
      mechanistic studies that examine the biological functions of HIF-2alpha when
      located in the cytoplasm.

PMID- 24565856
TI  - Extensor tendon entrapment after a Galeazzi-type paediatric fracture.

PMID- 24565857
TI  - Timed Sollerman hand function test for analysis of hand function in normal
      volunteers.
AB  - This study describes the development and application of the timed Sollerman hand
      function test in normal volunteers and the effect of age, gender, dominance and
      handedness on hand function. A total of 100 volunteers (50 men and 50 women) aged
      between 20 to 70 years were asked to complete the Sollerman hand function test.
      We measured the time taken to complete the 20 tasks using seven grips. Volunteers
      completed the tasks a mean of 20 seconds quicker with the dominant than with the
      nondominant hand. Individuals who are strongly right-handed showed a pronounced
      difference taking less time with the dominant hand. Women took less time to
      complete all tasks in age groups 30 to 40 years, than women in age groups 20 to
      30 years and beyond 40 years using the dominant hand. Men also showed worsening
      performance with age. The centile curves of the total time taken to complete all
      20 Sollerman tasks between the ages of 20 to 70 years will allow investigators to
      adjust their findings for age before attributing observed differences to disease
      or its treatment. 

PMID- 24565855
TI  - Phosphorous-containing polymers for regenerative medicine.
AB  - Disease and injury have resulted in a large, unmet need for functional tissue
      replacements. Polymeric scaffolds can be used to deliver cells and bioactive
      signals to address this need for regenerating damaged tissue. Phosphorous
      containing polymers have been implemented to improve and accelerate the formation
      of native tissue both by mimicking the native role of phosphorous groups in the
      body and by attachment of other bioactive molecules. This manuscript reviews the
      synthesis, properties, and performance of phosphorous-containing polymers that
      can be useful in regenerative medicine applications. 

PMID- 24565858
TI  - Using the internet to seek information about genetic and rare diseases: a case
      study comparing data from 2006 and 2011.
AB  - BACKGROUND: The Genetic and Rare Disease Information Center (GARD) is a major
      provider of Web-based information on genetic and rare diseases. Little is known
      about the type of Web-based information individuals seek about genetic and rare
      diseases or their reasons for seeking. OBJECTIVE: The objective of this paper is
      to describe the types of Web-based information sought about genetic and rare
      diseases and the reasons for seeking it from GARD by examining inquiries from
      2006 and 2011. METHODS: There were 278 English-language email and Web-based
      inquiries posed to GARD by lay individuals (ie, patients, parents, and
      relatives), which were randomly selected from inquiries in 2006 (n=68) and 2011
      (n=210) and examined using content analysis. RESULTS: Most often in both years,
      individuals sought basic disease information (51/68, 75.0% and 132/210, 62.8%;
      P=.067) and information about treatment (17/51, 33.3% and 62/132, 47.0%; P=.095).
      Specifically, inquirers requested information about their disease prognosis
      (6/51, 11.8% and 23/132, 17.4%; P=.347) and made requests for specialists (8/68,
      11.8% and 31/210, 14.8%; P=.536). In both 2006 and 2011, a substantial subset of
      inquirers requested information related to undiagnosed symptoms, representing
      16.2% (11/68) and 11.9% (25/210; P=.362) of inquiries, respectively. Inquirers
      were significantly more likely to have seen a health care provider before
      contacting GARD (99/210, 47.1% vs 20/68, 29.4%; P=.010) and to ask about clinical
      research studies in 2011 than in 2006 (24/210, 11.4% vs 2/68, 2.9%; P=.037). In
      the 2011 data set, the majority of the inquirers were women (201/210, 95.7%). In
      our 2006 sample, men were the majority source of inquiries (54/68, 79.4%).
      CONCLUSIONS: Findings from this study indicate that lay people contacting a
      genetic and rare disease information center most often seek information about
      disease prognosis, finding a specialist, and obtaining a diagnosis for symptoms.
      Unique characteristics of individuals searching the Internet for genetic and rare
      diseases information, includes a growing interest in participating in clinical
      research studies and a desire to supplement or better understand information
      discussed during a visit with a health care provider. These efforts represent
      advancements in patient self-advocacy.

PMID- 24565859
TI  - Application of the maximum cumulative ratio (MCR) as a screening tool for the
      evaluation of mixtures in residential indoor air.
AB  - The maximum cumulative ratio (MCR) method allows the categorisation of mixtures
      according to whether the mixture is of concern for toxicity and if so whether
      this is driven by one substance or multiple substances. The aim of the present
      study was to explore, by application of the MCR approach, whether health risks
      due to indoor air pollution are dominated by one substance or are due to
      concurrent exposure to various substances. Analysis was undertaken on monitoring
      data of four European indoor studies (giving five datasets), involving 1800
      records of indoor air or personal exposure. Application of the MCR methodology
      requires knowledge of the concentrations of chemicals in a mixture together with
      health-based reference values for those chemicals. For this evaluation, single
      substance health-based reference values (RVs) were selected through a structured
      review process. The MCR analysis found high variability in the proportion of
      samples of concern for mixture toxicity. The fraction of samples in these groups
      of concern varied from 2% (Flemish schools) to 77% (EXPOLIS, Basel, indoor), the
      variation being due not only to the variation in indoor air contaminant levels
      across the studies but also to other factors such as differences in number and
      type of substances monitored, analytical performance, and choice of RVs. However,
      in 4 out of the 5 datasets, a considerable proportion of cases were found where a
      chemical-by-chemical approach failed to identify the need for the investigation
      of combined risk assessment. Although the MCR methodology applied in the current
      study provides no consideration of commonality of endpoints, it provides a tool
      for discrimination between those mixtures requiring further combined risk
      assessment and those for which a single-substance assessment is sufficient. 

PMID- 24565860
TI  - Utility of specific biomarkers to assess safety of swine manure for
      biofertilizing purposes.
AB  - Swine production is an important economic activity in Brazil, and there is
      interest in the development of clean production mechanisms to support sustainable
      agro-industrial activities. The biomass derived from swine manure has good
      potential to be used as a biofertilizer due to its high nutrient concentration.
      However, the land application of manure should be based on safety parameters such
      as the presence of pathogens that can potentially infect animals and people. This
      study was designed to assess the presence of porcine circovirus-2 (PCV2), porcine
      adenovirus (PAdV), rotavirus-A (RV-A) and Salmonella spp. in liquid manure, as
      well the infectivity of two genotypes of circovirus-2 (PCV2a and PCV2b) present
      in liquid manure. Three swine farms were evaluated: 1) a nursery production farm
      (manure analyzed before and after anaerobic biodigestion), 2) a grow-finish
      production farm (analyzed before and after anaerobic biodigestion), and 3) a
      second grow-finish production farm (raw manure-affluent). PCV2, PAdV and RV-A
      were present before and after anaerobic biodigestion (either affluent or
      effluent) at all farms. Salmonella spp. were detected at farm 1 (affluent and
      effluent) and farm 3 (raw manure-affluent) but not farm 2 (affluent and
      effluent). When the ability of the anaerobic biodigestion process to reduce viral
      concentration was evaluated, no significant reduction was observed (P>0.05). Both
      the PCV2a and PCV2b genotypes were detected, suggesting viral co-infection in
      swine production. The results revealed infectious PCV2 even after anaerobic
      biodigestion treatment. The presence of Salmonella spp. and enteric viruses,
      especially infectious PCV2, in the final effluent from the anaerobic biodigester
      system suggests that the process is inefficient for pathogen inactivation. Due to
      the prevalence and infectivity of PCV2 and considering the successful use of
      molecular methods coupled to cell culture for detecting infectious PCV2, we
      suggest that this virus can be used as a bioindicator in swine manure treatment
      systems to check the efficiency of pathogen inactivation and ensure the
      production of safe biofertilizers from swine manure.

PMID- 24565861
TI  - Dissipation of sulfamethoxazole in pasture soils as affected by soil and
      environmental factors.
AB  - The dissipation of sulfamethoxazole (SMO) antibiotic in three different soils was
      investigated through laboratory incubation studies. The experiments were
      conducted under different incubation conditions such as initial chemical
      concentration, soil depth, temperature, and with sterilisation. The results
      indicate that SMO dissipated rapidly in New Zealand pasture soils, and the 50%
      dissipation times (DT50) in Hamilton, Te Kowhai and Horotiu soils under non
      sterile conditions were 9.24, 4.3 and 13.33 days respectively. During the
      incubation period for each sampling event the soil dehydrogenase activity (DHA)
      and the variation in microbial community were monitored thorough phospholipid
      fatty acid extraction analysis (PLFA). The DHA data correlated well with the
      dissipation rate constants of SMO antibiotic, an increase in the DHA activity
      resulted in faster antibiotic dissipation. The PLFA analysis was indicative of
      higher bacterial presence as compared to fungal community, highlighting the type
      of microbial community responsible for dissipation. The results indicate that
      with increasing soil depth, SMO dissipation in soil was slower (except for
      Horotiu) while with increase in temperature the antibiotic loss was faster, and
      was noticeable in all the soils. Both the degree of biological activity and the
      temperature of the soil influenced overall SMO dissipation. SMO is not likely to
      persist more than 5-6 months in all three soils suggesting that natural
      biodegradation may be sufficient for the removal of these contaminants from the
      soil. Its dissipation in sterile soils indicated abiotic factors such as strong
      sorption onto soil components to play a role in the dissipation of SMO.

PMID- 24565862
TI  - River-aquifer interactions and their relationship to stygofauna assemblages: a
      case study of the Gwydir River alluvial aquifer (New South Wales, Australia).
AB  - In contrast to surface water ecosystems, groundwater ecosystems are usually
      considered to have relatively stable conditions and physically inert
      environments. However, many groundwater ecosystems undergo substantial changes
      through space and time, related to fluxes in groundwater flow, exchange and
      nutrient imports. In this study we used hydrochemical data to: 1) determine the
      different hydrogeological conditions in an alluvial system, the shallow Gwydir
      River alluvial aquifer (located in Northern New South Wales, Australia); and 2)
      analyze the relationship between hydrochemical conditions and the composition of
      stygofauna assemblages in the aquifer. Using hydrochemical modeling and
      multivariate analyses, four main hydrogeological situations were defined as
      occurring in the aquifer. Bores were classified as having either a high, low or
      no influence from or exchange with the river. The latter group was further
      subdivided into those of low and high salinity. Further analysis combining the
      biological and hydrochemical data identified two main groups of samples. The
      first group was composed mainly of samples related to the aquifer groundwater
      which had higher richness and abundance of fauna compared to samples in the
      second group which was comprised of samples affected by stream water leakage and
      samples related to the highest salinities. These results suggest that more stable
      conditions (mainly related to steadier groundwater head levels) and lower nitrate
      concentrations promoted a more diverse and abundant stygofauna community. 

PMID- 24565863
TI  - Histone deacetylase 3 modulates Tbx5 activity to regulate early cardiogenesis.
AB  - Congenital heart defects often result from improper differentiation of cardiac
      progenitor cells. Although transcription factors involved in cardiac progenitor
      cell differentiation have been described, the associated chromatin modifiers in
      this process remain largely unknown. Here we show that mouse embryos lacking the
      chromatin-modifying enzyme histone deacetylase 3 (Hdac3) in cardiac progenitor
      cells exhibit precocious cardiomyocyte differentiation, severe cardiac
      developmental defects, upregulation of Tbx5 target genes and embryonic lethality.
      Hdac3 physically interacts with Tbx5 and modulates its acetylation to repress
      Tbx5-dependent activation of cardiomyocyte lineage-specific genes. These findings
      reveal that Hdac3 plays a critical role in cardiac progenitor cells to regulate
      early cardiogenesis. 

PMID- 24565864
TI  - CRB2 acts as a modifying factor of CRB1-related retinal dystrophies in mice.
AB  - Mutations in the CRB1 gene lead to retinal dystrophies ranging from Leber
      congenital amaurosis (LCA) to early-onset retinitis pigmentosa (RP), due to
      developmental defects or loss of adhesion between photoreceptors and Muller glia
      cells, respectively. Whereas over 150 mutations have been found, no clear
      genotype-phenotype correlation has been established. Mouse Crb1 knockout retinas
      show a mild phenotype limited to the inferior quadrant, whereas Crb2 knockout
      retinas display a severe degeneration throughout the retina mimicking the
      phenotype observed in RP patients associated with CRB1 mutations. Crb1Crb2 double
      mutant retinas have severe developmental defects similar to the phenotype
      observed in LCA patients associated with CRB1 mutations. Therefore, CRB2 is a
      candidate modifying gene of human CRB1-related retinal dystrophy. In this study,
      we studied the cellular localization of CRB1 and CRB2 in human retina and tested
      the influence of the Crb2 gene allele on Crb1-retinal dystrophies in mice. We
      found that in contrast to mice, in the human retina CRB1 protein was expressed at
      the subapical region in photoreceptors and Muller glia cells, and CRB2 only in
      Muller glia cells. Genetic ablation of one allele of Crb2 in heterozygote Crb1(+/
      ) retinas induced a mild retinal phenotype, but in homozygote Crb1 knockout mice
      lead to an early and severe phenotype limited to the entire inferior retina. Our
      data provide mechanistic insight for CRB1-related LCA and RP. 

PMID- 24565865
TI  - Analysis of non-synonymous-coding variants of Parkinson's disease-related
      pathogenic and susceptibility genes in East Asian populations.
AB  - To evaluate the contribution of non-synonymous-coding variants of known familial
      and genome-wide association studies (GWAS)-linked genes for Parkinson's disease
      (PD) to PD risk in the East Asian population, we sequenced all the coding exons
      of 39 PD-related disease genes and evaluated the accumulation of rare non
      synonymous-coding variants in 375 early-onset PD cases and 399 controls. We also
      genotyped 782 non-synonymous-coding variants of these genes in 710 late-onset PD
      cases and 9046 population controls. Significant enrichment of LRRK2 variants was
      observed in both early- and late-onset PD (odds ratio = 1.58; 95% confidence
      interval = 1.29-1.93; P = 8.05 * 10(-6)). Moderate enrichment was also observed
      in FGF20, MCCC1, GBA and ITGA8. Half of the rare variants anticipated to cause
      loss of function of these genes were present in healthy controls. Overall, non
      synonymous-coding variants of known familial and GWAS-linked genes appear to make
      a limited contribution to PD risk, suggesting that clinical sequencing of these
      genes will provide limited information for risk prediction and molecular
      diagnosis. 

PMID- 24565866
TI  - Unveiling the degradative route of the V247M alpha-sarcoglycan mutant responsible
      for LGMD-2D.
AB  - Many membrane and secretory proteins that fail to pass quality control in the
      endoplasmic reticulum (ER) are dislocated into the cytosol and degraded by the
      proteasome. In applying rigid rules, however, quality control sometimes
      discharges proteins that, even though defective, retain their function. The
      unnecessary removal of such proteins represents the pathogenetic hallmark of
      diverse genetic diseases, in the case of DeltaF508 mutant of cystic fibrosis
      transmembrane conductance regulator being probably the best known example.
      Recently, the inappropriate proteasomal degradation of skeletal muscle
      sarcoglycans (alpha, beta, gamma and delta) with missense mutation has been
      proposed to be at the bases of mild-to-severe forms of limb girdle muscular
      dystrophy (LGMD) known as type 2D, 2E, 2C and 2F, respectively. The quality
      control pathway responsible for sarcoglycan mutant disposal, however, is so far
      unexplored. Here we reveal key components of the degradative route of V247M alpha
      sarcoglycan mutant, the second most frequently reported mutation in LGMD-2D. The
      disclosure of the pathway, which is led by the E3 ligases HRD1 and RFP2, permits
      to identify new potential druggable targets of a disease for which no effective
      therapy is at present available. Notably, we show that the pharmacological
      inhibition of HRD1 activity rescues the expression of V247-alpha-sarcoglycan both
      in a heterologous cell model and in myotubes derived from a LGMD-2D patient
      carrying the L31P/V247M mutations. This represents the first evidence that the
      activity of E3 ligases, the enzymes in charge of mutant fate, can be eligible for
      drug interventions to treat sarcoglycanopathy. 

PMID- 24565867
TI  - A piggyBac insertion disrupts Foxl2 expression that mimics BPES syndrome in mice.
AB  - Blepharophimosis, ptosis, epicanthus inversus syndrome (BPES) is an autosomal
      dominant genetic disorder characterized by small palpebral fissures and other
      craniofacial malformations, often with (type I) but could also without (type II)
      premature ovarian failure. While mutations of the forkhead transcription factor
      FOXL2 are associated with and likely be responsible for many BPES cases, how
      FOXL2 affects craniofacial development remain to be understood. Through a large
      scale piggyBac (PB) insertion mutagenesis, we have identified a mouse mutant
      carrying a PB insertion ~160 kb upstream of the transcription start site (TSS) of
      Foxl2. The insertion reduces, but not eliminates, the expression of Foxl2. This
      mutant, but not its revertant, displays BPES-like conditions such as midface
      hypoplasia, eyelid abnormalities and female subfertility. Further analysis
      indicates that the mutation does not affect mandible, but causes premature fusion
      of the premaxilla-maxilla suture, smaller premaxilla and malformed maxilla during
      midface development. We further identified an evolutionarily conserved fragment
      near the insertion site and observed enhancer activity of this element in tissue
      culture cells. Analyses using DNase I hypersensitivity assay and chromosome
      conformation capture assay in developing maxillary and periocular tissues suggest
      that the DNA region near the insertion site likely interacts with Foxl2 TSS.
      Therefore, this mutant presents an excellent animal model for mechanistic study
      of BPES and regulation of Foxl2. 

PMID- 24565868
TI  - I know how you felt last night, or do I? Self- and external ratings of emotions
      in REM sleep dreams.
AB  - We investigated whether inconsistencies in previous studies regarding emotional
      experiences in dreams derive from whether dream emotions are self-rated or
      externally evaluated. Seventeen subjects were monitored with polysomnography in
      the sleep laboratory and awakened from every rapid eye movement (REM) sleep stage
      5 min after the onset of the stage. Upon awakening, participants gave an oral
      dream report and rated their dream emotions using the modified Differential
      Emotions Scale, whereas external judges rated the participants' emotions
      expressed in the dream reports, using the same scale. The two approaches produced
      diverging results. Self-ratings, as compared to external ratings, resulted in
      greater estimates of (a) emotional dreams; (b) positively valenced dreams; (c)
      positive and negative emotions per dream; and (d) various discrete emotions
      represented in dreams. The results suggest that this is mostly due to the
      underrepresentation of positive emotions in dream reports. Possible reasons for
      this discrepancy are discussed.

PMID- 24565869
TI  - Safety of inhaled (Tobi(r)) and intravenous tobramycin in young children with
      cystic fibrosis.
AB  - BACKGROUND: Use of inhaled tobramycin therapy for treatment of Pseudomonas
      aeruginosa infections in young children with cystic fibrosis (CF) is increasing.
      Safety data for pre-school children are sparse. METHODS: The aim of this study
      was to assess the safety of tobramycin solution for inhalation (TOBI(r)-TSI)
      administered twice daily for 2 months/course concurrently to intravenous (IV)
      tobramycin during P. aeruginosa eradication therapy in children (0-5 years).
      Audiological assessment and estimation of glomerular filtration rate (GFR) was
      measured prior to any exposure and end of the study. RESULTS: Data were available
      from 142 patients who were either never exposed to aminoglycosides (n=39),
      exposed to IV aminoglycosides only (n=36) or exposed to IV+TSI (n=67). Median
      exposure to TSI was 113 days [59, 119]. Comparison of effects on audiometry
      results and GFR, showed no detectable difference between the groups. CONCLUSIONS:
      Use of TSI and IV tobramycin in pre-school children with CF was not associated
      with detectable renal toxicity or ototoxicity.

PMID- 24565870
TI  - Bijective transformation circular codes and nucleotide exchanging RNA
      transcription.
AB  - The C(3) self-complementary circular code X identified in genes of prokaryotes
      and eukaryotes is a set of 20 trinucleotides enabling reading frame retrieval and
      maintenance, i.e. a framing code (Arques and Michel, 1996; Michel, 2012, 2013).
      Some mitochondrial RNAs correspond to DNA sequences when RNA transcription
      systematically exchanges between nucleotides (Seligmann, 2013a,b). We study here
      the 23 bijective transformation codes PiX of X which may code nucleotide
      exchanging RNA transcription as suggested by this mitochondrial observation. The
      23 bijective transformation codes PiX are C(3) trinucleotide circular codes,
      seven of them are also self-complementary. Furthermore, several correlations are
      observed between the Reading Frame Retrieval (RFR) probability of bijective
      transformation codes PiX and the different biological properties of PiX related
      to their numbers of RNAs in GenBank's EST database, their polymerization rate,
      their number of amino acids and the chirality of amino acids they code. Results
      suggest that the circular code X with the functions of reading frame retrieval
      and maintenance in regular RNA transcription, may also have, through its
      bijective transformation codes PiX, the same functions in nucleotide exchanging
      RNA transcription. Associations with properties such as amino acid chirality
      suggest that the RFR of X and its bijective transformations molded the origins of
      the genetic code's machinery. 

PMID- 24565871
TI  - Differences in the mobility of Cd, Cu, Pb and Zn during composting of two types
      of household bio-waste collected in four seasons.
AB  - The objective of this study was to evaluate the mobility of Cd, Cu, Pb and Zn
      during 3 different compost aeration rates of household bio-waste, originating in
      urban settlement (U-bio-waste) and family house buildings (F-bio-waste). The
      first two weeks, when the thermophilic composting phase became, the highest
      decline of exchangeable content was recorded. After 12 weeks of composting, lower
      exchangeable content was found in the case of U-bio-waste composts than F-bio
      waste composts, despite higher loss of fresh mass. The order of fractions in both
      final composts was as follows: residual>oxidizable>reducible>exchangeable. The
      exchangeable portion of total content in final composts decreased in this order:
      Zn (17%), Cd (11%), Pb (4%) and Cu (3%). Regarding the low exchangeable content
      of heavy metals and high-quality organic matter, these types of composts could be
      used not only as fertilizer, but for remediation of metals contaminated land.

PMID- 24565872
TI  - Effects of plant biomass on denitrifying genes in subsurface-flow constructed
      wetlands.
AB  - The effect of Typha latifolia and its litter on density and abundance of three
      denitrifying genes (nirS, nirK and nosZ) were investigated in six laboratory
      scale SSF CW microcosms. Results showed that the copy numbers of nirS, nirK and
      nosZ in wetland microcosms were ranged between 10(8)-10(9), 10(6)-10(7) and 10(7)
      10(8) copies g(-1), respectively. The presence of T. latifolia encouraged the
      growth of nirK containing bacteria. Addition of cattail litter could greatly
      stimulate the growth of bacteria containing nirS and nosZ gene. Path analysis
      illustrated that the presence of plants and litters had no significant direct
      impact on denitrifying genes, while it affected the denitrifying genes via
      alteration of dissolved oxygen and carbon sources. 

PMID- 24565873
TI  - Biosorbents for recovery of precious metals.
AB  - Biosorption is a promising technology not only for the removal of heavy metals
      and dyes but also for the recovery of precious metals (PMs) from solution phases.
      The biosorptive recovery of PMs from waste solutions and secondary resources is
      recently getting paid attractive attention because their price is increasing or
      fluctuating, their available deposit is limited and maldistributed, and high-tech
      industries need more consumption of PMs. The biosorbents for recovery of PMs
      require specifications which differ from those for the treatment of wastewaters
      containing heavy metals and dyes. In this review, the previous works on
      biosorbents and biosorption for recovery of PMs were summarized. Especially, we
      discuss and suggest the required specifications of biosorbents for recovery of
      PMs and strategies to give the required properties to the biosorbents. We believe
      this review will provide useful information to scientists and engineers and hope
      to give insights into this research frontier. 

PMID- 24565874
TI  - Enzymatic electrosynthesis of formate through CO2 sequestration/reduction in a
      bioelectrochemical system (BES).
AB  - Bioelectrochemical system (BES) was operated using the enzyme formate
      dehydrogenase as catalyst at cathode in its free form for the reduction of CO2
      into formic acid. Electrosynthesis of formic acid was higher at an operational
      voltage of -1V vs. Ag/AgCl (9.37mgL(-1) CO2) compared to operation at -0.8V
      (4.73mgL(-1) CO2) which was strongly supported by the reduction catalytic
      current. Voltammograms also depicted a reversible redox peak throughout operation
      at -1V, indicating NAD(+) recycling for proton transfer from the source to CO2.
      Saturation of the product was observed after 45min of enzyme addition and then
      reversibility commenced, depicting a lower and stable formic acid concentration
      throughout the subsequent time of operation. Stability of the enzyme activity
      after immobilization on the electrode and product yield will be studied further. 

PMID- 24565875
TI  - Bioremoval and recovery of Cd(II) by Pseudoalteromonas sp. SCSE709-6: Comparative
      study on growing and grown cells.
AB  - Comparison of the bioremoval and recovery of Cd(II) by growing and grown marine
      bacterium Pseudoalteromonas sp. SCSE709-6 was performed in batch systems.
      Bioremoval with growing cells (Sorption I) showed better performance at low
      Cd(II) concentrations, whereas bioremoval with grown cells (Sorption II) had
      significant advantages in both removal efficiency and time consumption at high
      Cd(II) concentrations. The optimal pH was higher for Sorption I than for Sorption
      II for achieving the maximum Cd(II) removal efficiency. Complete desorption was
      achieved using either Na2EDTA or HNO3 as eluent. Cd(II) adsorbed on grown cells
      had higher tendency to be desorbed. Na2EDTA was a preferable eluent for the
      recycling biomaterials, whereas HNO3 performed better for the final security
      disposal of sludge. For Sorption II, both Langmuir and Freundlich isotherms well
      explained the biosorption behavior, and the pseudo-second-order model better
      expressed biosorption and desorption kinetics. 

PMID- 24565877
TI  - Separation of lignocelluloses from spent liquor of NSSC pulping process via
      adsorption.
AB  - Hemicelluloses and lignin present in the spent liquor (SL) of neutral sulfite
      semichemical (NSSC) pulping process can potentially be converted into value-added
      products such as furfural, hydroxymethylfurfural, levulinic acid, phenols and
      adhesives. However, the direct conversion of hemicelluloses and lignin of SL into
      value-added products is uneconomical due to the dilute nature of the SL. To have
      a feasible downstream process for utilizing lignocelluloses of SL, the
      lignocelluloses should initially be separated from the SL. In this study, an
      adsorption process (via applying activated carbon) was considered for isolating
      the dissolved lignin and hemicelluloses from the SL of an NSSC pulping process.
      Under the optimal conditions of pH, SL/AC weight ratio, time and temperature of
      5.7, 30, 360 min and 30  degrees C, the maximum lignin and hemicellulose
      adsorptions were 0.33 and 0.25 g/g on AC. The chemical oxygen demand (COD) and
      turbidity of the SL were decreased by 11% and 39%, respectively, as a result of
      lignocellulose adsorption on AC. Also, the incineration behavior of the SL
      treated AC was studied with a thermo-gravimetric analysis (TGA). 

PMID- 24565878
TI  - Values of decentralized systems that avoid investments in idle capacity within
      the wastewater sector: a theoretical justification.
AB  - In this work, the values of decentralized (onsite) systems that avoid investments
      in idle capacity within wastewater plans are quantitatively justified using the
      specific net present value (SNPV) approach. SNPV is a currently proposed
      criterion in environmental engineering economics that is defined as the net
      present value of the cost per unit of service or per population equivalent (PE).
      The SNPV approach was reintroduced with bugs fixed and then applied to the
      economic analysis of the capital and operating costs of one-stage completed
      central plants, stage-expanded central plants, and decentralized treatment
      facilities. The results show that under a demand growth scenario, the central
      plant will inevitably reach idle capacity, which can be reduced by a staged
      expansion. However, the staged expansion plan will lose the economies of scale
      and, hence, is only viable under projections of a low or moderate price inflation
      rate or high demand growth rate. Onsite treatment systems can theoretically
      achieve 100% utilization. Assuming that the capital costs per PE of the onsite
      and central systems are equal, the former is economically favorable in most cases
      of price inflation as a result of its cost saving on idle capacity. Onsite
      treatment systems can be viable even though their capital expenditures per PE are
      higher than that of a comparable centralized option as to a capital investment.
      This finding suggests wide opening of onsite technology choices. Use of the SNPV
      showed that average operating expenses of centralized plants decrease as demand
      growth rates increase as a benefit of economies of scale, whereas those of onsite
      treatment systems depend only on price inflation. Semi-decentralized systems
      feature both the financial advantage of the onsite system (capital investment)
      and the superiority of centralized systems (operation and maintenance); thus, it
      is worth consideration. The results of this study illustrate not only the value
      of decentralized systems but also the value of the SNPV approach in the planning
      of wastewater services, especially in areas undergoing high demand growth. 

PMID- 24565879
TI  - Myocardial infarction in a young man due to coronary artery aneurysms after an
      undiagnosed Kawasaki disease.
AB  - BACKGROUND: Kawasaki disease usually affects infants and young children. It often
      goes unrecognized in adults due to varying symptoms and lack of definite
      diagnostic criteria. OBJECTIVES: To describe the potential for acute myocardial
      infarction as a complication of antecedent Kawasaki Disease (KD). CASE REPORT: We
      describe a case of a 19-year-old man who presented to the Emergency Department
      (ED) with an acute myocardial infarction that was subsequently determined to be
      the result of previously untreated KD. CONCLUSION: Kawasaki disease can cause
      coronary complications in a teenager. A high level of suspicion in the ED can
      help in proper management of these patients.

PMID- 24565880
TI  - Emphysematous vasitis misdiagnosed as strangulated inguinal hernia.

PMID- 24565881
TI  - Health, emergency department use, and early identification of young children
      exposed to trauma.
AB  - BACKGROUND: Childhood trauma is an important public health problem with
      financial, physical health, and mental health repercussions. Emergency
      departments (EDs) are often the first point of contact for many young children
      affected by emotionally or psychologically traumatic events (e.g., neglect,
      separation from primary caregiver, maltreatment, witness to domestic violence
      within the family, natural disasters). STUDY OBJECTIVES: Describe the prevalence
      of physical health symptoms, ED use, and health-related problems in young
      children (birth through 5 years) affected by trauma, and to predict whether or
      not children experiencing trauma are more likely to be affected by health-related
      problems. METHODS: Community-based, cross-sectional survey of 208 young children.
      Traumatic events were assessed by the Traumatic Events Screening Inventory -
      Parent Report Revised. Child health symptoms and health-related problems were
      measured using the Caregiver Information Questionnaire, developed by ORC Macro
      (Atlanta, GA). RESULTS: Seventy-two percent of children had experienced at least
      one type of traumatic event. Children exposed to trauma were also experiencing
      recent health-related events, including visits to the ED (32.2%) and the doctor
      (76.9%) for physical health symptoms, and recurring physical health problems
      (40.4%). Children previously exposed to high levels of trauma (four or more types
      of events) were 2.9 times more likely to report having had recently visited the
      ED for health purposes. CONCLUSIONS: Preventing recurrent trauma or recognizing
      early trauma exposure is difficult, but essential if long-term negative
      consequences are to be mitigated or prevented. Within EDs, there are missed
      opportunities for identification and intervention for trauma-exposed children, as
      well as great potential for expanding primary and secondary prevention of
      maltreatment-associated illness, injury, and mortality.

PMID- 24565882
TI  - Adverse drug event nonrecognition in emergency departments: an exploratory study
      on factors related to patients and drugs.
AB  - BACKGROUND: Many adverse drug events (ADEs) are not identified by emergency
      physicians. Research has been done to study risk factors for ADEs and help
      emergency physicians diagnose ADEs. However, no research has specifically
      examined the causes underlying a lack of attribution of ADEs to medications in
      emergency department (ED) patients. OBJECTIVE: We conducted an exploratory study
      in a medical ED to search for the factors associated with ADE nonrecognition that
      are related to ED patients and ADEs. METHODS: We conducted an observational study
      in the medical ED of a French tertiary care hospital between January and December
      2009. The study focused on all ADEs, whether or not they were related to the
      patient's chief complaint. ADEs were identified by an expert physician and
      pharmacist based on National Electronic Injury Surveillance System criteria. An
      ADE was considered "attributed" if any evidence of ADE suspicion, ADE diagnosis,
      or ADE management was documented on ED charts. Factors associated with ADE
      nonrecognition were identified using multiple logistic regression analysis.
      RESULTS: Of the 465 included patients, 90 experienced an ADE at ED visit (19.4%;
      95% confidence interval [CI] 15.9%-23.2%). Emergency physicians correctly
      recognized 36 of these cases (40.0%; 95% CI 29.8%-50.9%). On multivariate
      analysis, ADE nonrecognition was significantly associated with the following
      variables: nonrelation between the ADE and the patient's chief complaint; daily
      prescription of four drugs or more; and hospitalization ADE severity category.
      CONCLUSIONS: Our results emphasize the importance of searching for ADEs in
      patients with daily polypharmacy or whose chief complaint does not seem to be
      drug related.

PMID- 24565883
TI  - Invisible ingested foreign body: aluminum can top.

PMID- 24565884
TI  - Hourly rounding in the pediatric emergency department: patient and family safety
      and satisfaction rounds.
AB  - BACKGROUND: Methods of increasing patient and family involvement in and
      understanding of their medical care are plentiful, and hourly rounding
      specifically has shown benefit in several clinical settings. Although the
      approach has shown a variety of advantages in other areas, its use in urgent care
      pediatric settings is not well described. OBJECTIVES: This study evaluates the
      institution of patient satisfaction and safety rounding ("hourly rounding") in
      the pediatric emergency department (ED) setting. METHODS: Hourly rounding was
      instituted in a tertiary care, urban pediatric ED using a formal mnemonic, after
      staff education, training, and observation to ensure standardization of approach.
      Pre- and postintervention data were collected, including frequency and type of
      nursing call bell usage, family discharge opinion survey, and vendor-collected
      survey results. RESULTS: Two weeks of nursing call bell activation data and 200
      pre- and postintervention family discharge opinion surveys were collected, evenly
      divided between pre- and postimplementation data. Call bell activations prior to
      and after hourly rounding institution were 102 and 150 respectively, with
      accidental activations comprising the majority. Additionally, vendor-collected
      patient satisfaction data were analyzed. There were no changes in patient scoring
      when pre- and postimplementation data were compared. CONCLUSIONS: This model of
      hourly rounding shows no measurable improvement in patient satisfaction or
      provider-patient communication using call bell data, family discharge opinion
      surveys, or vendor-collected patient satisfaction data. Further studies may be
      indicated to identify different methods of analyzing the effects of this method,
      and to examine alternative methods of improving these outcomes in the pediatric
      ED setting.

PMID- 24565885
TI  - Synthetic cathinones ("bath salts").
AB  - BACKGROUND: Synthetic cathinones are popularly referred to in the media as "bath
      salts." Through the direct and indirect activation of the sympathetic nervous
      system, smoking, snorting, or injecting synthetic cathinones can result in
      tachycardia, hypertension, hyperthermia, myocardial infarction, and death.
      OBJECTIVE: The chemical structures and names of bath salts identified by the Ohio
      Attorney General's Bureau of Criminal Investigation are presented. Based on their
      common pharmacophores, we review the history, pharmacology, toxicology, detection
      methods, and clinical implications of synthetic cathinones. Through the
      integration of this information, the pharmacological basis for the management of
      patients using synthetic cathinones is presented. DISCUSSION: Synthetic
      cathinones activate central serotonergic and dopaminergic systems contributing to
      acute psychosis and the peripheral activation of the sympathetic nervous system.
      The overstimulation of the sympathetic nervous system contributes to the many
      toxicities reported with bath salt use. The pharmacological basis for managing
      these patients is targeted at attenuating the activation of these systems.
      CONCLUSIONS: Treatment of patients presenting after using bath salts should be
      focused on reducing agitation and psychosis and supporting renal perfusion. The
      majority of successfully treated synthetic cathinones cases have used
      benzodiazepines and antipsychotics along with general supportive care.

PMID- 24565886
TI  - Retention of insulin-like growth factor I bioactivity during the fabrication of
      sintered polymeric scaffolds.
AB  - The use of growth factors in tissue engineering offers an added benefit to
      cartilage regeneration. Growth factors, such as insulin-like growth factor I (IGF
      I), increase cell proliferation and can therefore decrease the time it takes for
      cartilage tissue to regrow. In this study, IGF-I was released from poly(lactic-co
      glycolic acid) (PLGA) scaffolds that were designed to have a decreased burst
      release often associated with tissue engineering scaffolds. The scaffolds were
      fabricated from IGF-I-loaded PLGA microspheres prepared by a double emulsion
      (W1/O/W2) technique. The microspheres were then compressed, sintered at 49 
      degrees C and salt leached. The bioactivity of soluble IGF-I was verified after
      being heat treated at 37, 43, 45, 49 and 60  degrees C. Additionally, the
      bioactivity of IGF-I was confirmed after being released from the sintered
      scaffolds. The triphasic release lasted 120 days resulting in 20%, 55% and 25% of
      the IGF-I being released during days 1-3, 4-58 and 59-120, respectively. Seeding
      bone marrow cells directly onto the IGF-I-loaded scaffolds showed an increase in
      cell proliferation, based on DNA content, leading to increased glycosaminoglycan
      production. The present results demonstrated that IGF-I remains active after
      being incorporated into heat-treated scaffolds, further enhancing tissue
      regeneration possibilities.

PMID- 24565887
TI  - URAM scale for functional assessment in Dupuytren's disease: a comparative study
      of its properties.
AB  - OBJECTIVE: To test the convergent validity and ease of use of the Unite
      Rhumatologique des Affections de la Main (URAM) scale for patients with
      Dupuytren's disease. METHODS: Patients were prospectively included. We compared
      the convergent validity of the URAM scale, the Cochin Hand Function Scale (CHFS)
      and the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire, in terms
      of their correlation with the Tubiana score and self-assessed disability on a
      visual analog scale (VAS). Pearson's correlation was used for the convergent
      validity study. The response time for questionnaire completion was the outcome
      for ease of implementation. RESULTS: We included 53 patients with Dupuytren's
      disease in the convergent validity study and 30 other patients with the disease
      in the time-response assessment. The URAM scale showed strong convergence with
      the Tubiana scale (r=0.64) and self-assessed disability on a VAS (r=0.69).
      Convergence with the Tubiana and self-assessed disability was higher for the URAM
      scale than the CHFS or DASH questionnaire. The mean [SD] response time was
      shorter for the URAM scale than the CHFS or DASH questionnaire (42 [20] vs 71
      [35] and 103 [59] s, respectively, P<0.0001). CONCLUSIONS: The results reinforce
      the psychometric merits of the URAM scale. Furthermore, the response time for
      assessing disability was shorter with the URAM scale than the CHFS or DASH
      questionnaire. This evidence supports the high recommendation for the use of the
      URAM scale in clinical practice and clinical studies to assess disability in
      Dupuytren's disease.

PMID- 24565888
TI  - Serum uric acid and cardiovascular risk: state of the art and perspectives.
AB  - Hyperuricaemia is commonly found in subjects with cardiovascular disease, but its
      role as risk factor is very controversial. Although several studies reported
      serum uric acid as a marker of an underlying pathophysiological process, other
      studies hypothesis a potential causal link between serum uric acid and
      cardiovascular diseases. Some studies suggest that uric acid is biologically
      active and may have an atherogenesis role in development of cardiovascular
      diseases, although the mechanisms are not fully understood. Other studies have
      shown that uric acid can independently predict the development of some
      cardiovascular risk factors such as hypertension and metabolic syndrome, as well
      as myocardial infarction and stroke. The relations between serum uric acid and
      established cardiovascular risk factors are complex, and these latter could be
      considered as confounding factors. In this report, we review the inextricably
      link of serum uric acid to known cardiovascular risk factors, and we describe the
      possible mechanisms and potential causative role between serum uric acid and
      cardiovascular events in the general population, in subjects with cardiovascular
      risk factors and in those with pre-existing cardiovascular diseases. Limited
      information however is available concerning the impact of urate-lowering
      treatments on cardiovascular events, whereas only a positive therapeutic trial
      could give definite answers to the difficult problem of causality of uric acid in
      relation to cardiovascular risk. Thus, it is time to propose the design of a
      therapeutic trial, integrating cardiologists and rheumatologists, in order to
      further decrease cardiovascular risk.

PMID- 24565889
TI  - Endothelial dysfunction in joint disease.
AB  - Inflammatory joint diseases and autoimmune diseases with joint manifestations are
      associated with premature and accelerated atherogenesis. Patients with rheumatoid
      arthritis (RA) have a 5- to 10-year decrease in life expectancy compared to the
      general population, and those exhibiting extraarticular manifestations have the
      greatest excess mortality. RA is now established as an independent cardiovascular
      risk factor. Complex interactions linking conventional cardiovascular risk
      factors, systemic inflammation, and vascular function may explain the increased
      cardiovascular risk among RA patients. Endothelial dysfunction is now recognized
      as both the key step in early atherogenesis and a contributor to atheroma plaque
      progression at later stages. Endothelial dysfunction is defined as impaired
      endothelium-dependent blood-vessel dilation in response to a stimulus. The
      underlying mechanisms remain speculative. Over the last decade, a role for
      endothelial dysfunction in the cardiovascular complications of inflammatory joint
      disease has been hypothesized and several maintenance drugs targeting this
      phenomenon have been tested, with promising results.

PMID- 24565890
TI  - Identification of organic acids as potential biomarkers in the urine of autistic
      children using gas chromatography/mass spectrometry.
AB  - There is a need to identify metabolic phenotypes in autism as they might each
      require unique approaches to prevention. Biological markers can help define
      autism subtypes and reveal potential therapeutic targets. The aim of the study
      was to identify alterations of small molecular weight compounds and to find
      potential biomarkers. Gas chromatography/mass spectrometry was employed to
      evaluate major metabolic changes in low molecular weight urine metabolites of 14
      children with autism spectrum disorders vs. 10 non-autistic subjects. The results
      prove the usefulness of an identified set of 21 endogenous compounds (including
      14 organic acids), whose levels are changed in diseased children. Gas
      chromatography/mass spectrometry method combined with multivariate statistical
      analysis techniques provide an efficient way of depicting metabolic perturbations
      of diseases, and may potentially be applicable as a novel strategy for the
      noninvasive diagnosis and treatment of autism. 

PMID- 24565891
TI  - Habitual dietary intake impacts on the lipidomic profile.
AB  - Reliable dietary assessments are essential when attempting to understand the
      complex links between diet and health. Traditional methods for collecting dietary
      exposure can be unreliable, therefore there is an increasing interest in
      identifying biomarkers to provide a more accurate measurement. Metabolomics is a
      technology that offers great promise in this area. The aim of this study was to
      use a multivariate statistical strategy to link lipidomic patterns with dietary
      data in an attempt to identify dietary biomarkers. We assessed the relationship
      between lipidomic profiles and dietary data in volunteers (n=34) from the
      Metabolic Challenge Study (MECHE). Principal component analysis (PCA), linear
      regression and receiver operating characteristic (ROC) analysis were used to (1)
      reduce the lipidomic data into lipid patterns (LPs), (2) investigate
      relationships between these patterns and dietary data and (3) identify biomarkers
      of dietary intake. Our study identified a total of 6 novel LPs. LP1 was highly
      predictive of dietary fat intake (area under the curve AUC=0.82). A random forest
      (RF) classification model used to discriminate between low and high consumers
      resulted with an error rate of >10%, with a panel of six metabolites identified
      as the most predictive. LP4 was highly predictive of alcohol intake (AUC=0.81)
      with lysophosphatidylcholine alkyl C18:0 (LPCeC18:0) identified as a potential
      biomarker of alcohol consumption. LP6 had a reasonably good ability to predict
      dietary fish intake (AUC=0.76), with lysophosphatidylethanolamine acyl C18:2
      (LPEaC18:2) phoshatidylethanolamine diaclyl C38:4 (PEaaC38:4) identified as
      potential biomarkers. The identification of these LPs and specific biomarkers
      will help in better classifying a persons dietary intake and in turn will improve
      the assessment of the relationship between diet and disease. Linking these LPs
      and specific biomarkers with health parameters will be an important future step. 

PMID- 24565892
TI  - Update on primary sclerosing cholangitis genetics.
AB  - PURPOSE OF REVIEW: The pathogenesis of primary sclerosing cholangitis (PSC)
      involves heritable factors. This review summarizes the recent genetic studies and
      discusses the implications of identified risk loci. RECENT FINDINGS: A total of
      16 PSC susceptibility loci have been identified in genome-wide association
      studies and related study designs. At least 33 additional loci are involved in
      what is increasingly acknowledged to represent a general pool of genetic risk
      loci for immune-mediated diseases. One important group of genes is part of well
      characterized immune pathways (e.g. interleukin 2 signaling), whereas for other
      loci the relationship to PSC pathophysiology is less evident. Importantly, the
      loci collectively account for only 7.3% of overall PSC liability, thus pointing
      to a large contribution from environmental factors to PSC development. The
      individual PSC risk genes cannot be interpreted within a simple cause-effect
      model used for monogenic traits, but need to be explored for their individual
      biological correlates, preferably in a disease context. To some extent, as
      exemplified for the human leukocyte antigen and FUT2 associations, genetic
      findings may guide the discovery of interacting and co-occuring environmental
      susceptibility factors. SUMMARY: Multiple PSC susceptibility loci are now
      available for exploration in experimental model systems and patient-centered
      research.

PMID- 24565893
TI  - A co culture approach show that polyamine turnover is affected during
      inflammation in Atlantic salmon immune and liver cells and that arginine and LPS
      exerts opposite effects on p38MAPK signaling.
AB  - This study assess which pathways and molecular processes are affected by exposing
      salmon head kidney cells or liver cells to arginine supplementation above the
      established requirements for growth support. In addition to the conventional mono
      cultures of liver and head kidney cells, co cultures of the two cell types were
      included in the experimental set up. Responses due to elevated levels of arginine
      were measured during inflammatory (lipopolysaccharide/LPS) and non -inflammatory
      conditions. LPS up regulated the genes involved in polyamine turnover; ODC
      (ornithine decarboxylase), SSAT (spermidine/spermine-N1-acetyltransferase) and
      SAMdc (S-adenosyl methionine decarboxylase) in head kidney cells when co cultured
      with liver cells. Regardless of treatment, liver cells in co culture up regulated
      ODC and down regulated SSAT when compared to liver mono cultures. This suggests
      that polyamines have anti-inflammatory properties and that both salmon liver
      cells and immune cells seem to be involved in this process. The transcription of
      C/EBP beta/CCAAT, increased during inflammation in all cultures except for liver
      mono cultures. The observed up regulation of this gene may be linked to glucose
      transport due to the highly variable glucose concentrations found in the cell
      media. PPARalpha transcription was also increased in liver cells when receiving
      signals from head kidney cells. Gene transcription of Interleukin 1beta (IL
      1beta), Interleukin-8 (IL-8), cyclooxygenase 2 (COX2) and CD83 were elevated
      during LPS treatment in all the head kidney cell cultures while arginine
      supplementation reduced IL-1beta and IL-8 transcription in liver cells co
      cultured with head kidney cells. This is probably connected to p38MAPK signaling
      as arginine seem to affect p38MAPK signaling contrary to the LPS induced p38MAPK
      signaling, suggesting anti-inflammatory effects of arginine/arginine metabolites.
      This paper shows that co culturing these two cell types reveals the connection
      between metabolism and inflammation, suggesting different pathways and candidate
      biomarkers to be further explored. 

PMID- 24565894
TI  - Cloning and expression analyses of interferon regulatory factor (IRF) 3 and 7
      genes in European eel, Anguilla anguilla with the identification of genes
      involved in IFN production.
AB  - Interferon regulatory factor (IRF) 3 and IRF7 have been identified as regulators
      of type I interferon (IFN) gene expression in mammals. In the present study, the
      two genes were cloned and characterized in the European eel, Anguilla anguilla.
      The full-length cDNA sequence of IRF3 and IRF7 in the European eel, named as
      AaIRF3 and AaIRF7 consists of 2879 and 2419 bp respectively. Multiple alignments
      showed that the two IRFs have a highly conserved DNA binding domain (DBD) in the
      N terminus, with the characteristic motif containing five tryptophan residues,
      which is a feature present in their mammalian homologues. But, IRF7 has only four
      of the five residues in other species of fish. The expression of AaIRF3 and
      AaIRF7 both displayed an obvious dose-dependent manner following
      polyinosinic:polycytidylic acid (PolyI:C) challenge. In vivo expression analysis
      showed that the mRNA level of AaIRF3 and AaIRF7 was significantly up-regulated in
      response to PolyI:C stimulation in all examined tissues/organs except in muscle,
      with a lower level of increase observed in response to lipopolysaccharide (LPS)
      challenge and Edwardsiella tarda infection, indicating that AaIRF3 and AaIRF7 may
      be more likely involved in antiviral immune response. In addition, some pattern
      recognition receptors genes related with the production of type I IFNs and those
      genes in response to type I IFNs were identified in the European eel genome
      database, indicating a relatively conserved system in the production of type I
      IFN and its signalling in the European eel. 

PMID- 24565895
TI  - Preclinical pharmacology of FL442, a novel nonsteroidal androgen receptor
      modulator.
AB  - The preclinical profiles of two most potent compounds of our recently published
      cycloalkane[d]isoxazole pharmacophore-based androgen receptor (AR) modulators,
      FL442 (4-(3a,4,5,6,7,7a-hexahydro-benzo[d]isoxazol-3-yl)-2
      (trifluoromethyl)benzonitrile) and its nitro analog FL425 (3-(4-nitro-3
      (trifluoromethyl)phenyl)-3a,4,5,6,7,7a-hexahydrobenzo[d]isoxazole), were explored
      to evaluate their druggability for the treatment of AR dependent prostate cancer.
      The studies revealed that both compounds are selective to AR over other closely
      related steroid hormone receptors and that FL442 exhibits equal inhibition
      efficiency towards the androgen-responsive LNCaP prostate cancer cell line as the
      most widely used antiandrogen bicalutamide and the more recently discovered
      enzalutamide. Notably, FL442 maintains antiandrogenic activity with enzalutamide
      activated AR mutant F876L. In contrast to bicalutamide, FL442 does not stimulate
      the VCaP prostate cancer cells which express elevated levels of the AR.
      Distribution analyses showed that [(14)CN]FL442 accumulates strongly in the mouse
      prostate. In spite of its low plasma concentration obtained by intraperitoneal
      administration, FL442 significantly inhibited LNCaP xenograft tumor growth. These
      findings provide a preclinical proof for FL442 as a promising AR targeted
      candidate for a further optimization. 

PMID- 24565896
TI  - (1)H NMR metabolic profiling analysis offers evaluation of Nilestriol treatment
      in ovariectomised rats.
AB  - Nilestriol (NIL) has been applied to treat menopausal dysfunctions, yet its
      mechanism has remained unknown. To understand the relationship between the
      changes in homeostatic metabolites and ovarian oestrogen deficiency syndromes
      after NIL treatment, proton Nuclear Magnetic Resonance ((1)H NMR)-based
      metabonomic technologies were used to analyse a rat model of oestrogen
      deficiency. An orthogonal partial least-squares regression (OPLS) differentiation
      model was used on 12-week metabolic analyses of ovariectomised (OVX) rats treated
      or mock treated with NIL. Furthermore, data analysis using Chenomx software
      quantified results to identify the most significantly altered metabolite
      concentrations, allowing for metabolic explanations of the effects of NIL
      therapies. In this study, PLS results revealed that there are considerably
      distinct differences between treatment groups. Additionally, a total of 45
      metabolites shown to have a high variation between groups were selected for
      target quantification. Using a one-way LSD ANOVA analysis, 32 metabolite
      concentrations were significantly altered in the OVX group. A total of 21
      metabolites were altered significantly in the NIL-treatment group but later
      returned to normal. According to the OPLS VIP calculation, the metabolites most
      affected by NIL treatment were mostly involved in insulin resistance. In
      addition, abnormal concentration changes in lactate in the NIL-treatment group
      and 3-indoxylsulfate in the OVX group were observed. To our knowledge, this study
      is the first to address the molecular mechanism of NIL from a metabonomic
      perspective, and, more specifically, to establish a catalogue of endo-molecular
      changes effected by NIL in the regulation of oestrogen deficiency disorder. 

PMID- 24565897
TI  - Carboxyl-terminal multi-site phosphorylation regulates internalization and
      desensitization of the human sst2 somatostatin receptor.
AB  - The somatostatin receptor 2 (sst2) is the pharmacological target of somatostatin
      analogs that are widely used in the diagnosis and treatment of human
      neuroendocrine tumors. We have recently shown that the stable somatostatin
      analogs octreotide and pasireotide (SOM230) stimulate distinct patterns of sst2
      receptor phosphorylation and internalization. Like somatostatin, octreotide
      promotes the phosphorylation of at least six carboxyl-terminal serine and
      threonine residues namely S341, S343, T353, T354, T356 and T359, which in turn
      leads to a robust receptor endocytosis. Unlike somatostatin, pasireotide
      stimulates a selective phosphorylation of S341 and S343 of the human sst2
      receptor followed by a partial receptor internalization. Here, we show that
      exchange of S341 and S343 by alanine is sufficient to block pasireotide-driven
      internalization, whereas mutation of T353, T354, T356 and T359 to alanine is
      required to strongly inhibited both octreotide- and somatostatin-induced
      internalization. Yet, combined mutation of T353, T354, T356 and T359 is not
      sufficient to prevent somatostatin-driven beta-arrestin mobilization and receptor
      desensitization. Replacement of all fourteen carboxyl-terminal serine and
      threonine residues by alanine completely abrogates sst2 receptor internalization
      and beta-arrestin mobilization in HEK293 cells. Together, our findings
      demonstrate for the first time that agonist-selective sst2 receptor
      internalization is regulated by multi-site phosphorylation of its carboxyl
      terminal tail. 

PMID- 24565898
TI  - Covalent TiO(2)/pectin microspheres with Fe(3)O(4) nanoparticles for magnetic
      field-modulated drug delivery.
AB  - Covalent TiO(2)-co-pectin microspheres containing Fe(3)O(4) nanoparticles were
      developed through an ultrasound-induced crosslinking/polymerization reaction
      between the glycidyl methacrylate from vinyl groups in TiO(2) and in pectin. zeta
      potentials became less negative in the nanostructured microspheres, caused by the
      presence of both inorganic particles in the negatively charged pectin. The
      nanostructured pectin microspheres showed an amoxicillin release rate slower than
      that of pure pectin microspheres. The proposed microspheres were found to be a
      sustained release system of amoxicillin in the acid medium. Furthermore, the
      antibiotic release may be modulated by exposition of the microspheres to a remote
      magnetic field. In practical terms, the nanostructured microspheres could deliver
      a larger proportion of their initial load to specific site of action. The
      cytotoxic concentrations for 50% of VERO cells (CC(50)), calculated as the
      concentration required to reduce cell viability by 50% after 72h of incubation,
      for pectin-only microspheres and nanostructured pectin microspheres were 217.7+/
      6.5 and 121.5+/-4.9MUgmL(-1), respectively. The obtained CC(50) values indicated
      acceptable cytotoxic levels for an incubation period of 72h, showing that the
      pectin microspheres have a great pharmacological potential for uses in biological
      environments, even after the introduction of both Fe(3)O(4) and TiO(2).

PMID- 24565899
TI  - Chronotherapeutic delivery of hydroxypropylmethylcellulose based mini-tablets: an
      in vitro-in vivo correlation.
AB  - The purpose of the study was to develop and internally validate a nonlinear in
      vitro-in vivo correlation model for a chronotherapeutically programmed HPMC based
      propranolol HCl (PHCl) mini-tablet. A simple and sensitive HPLC method was
      developed for the determination of PHCl content in rabbit plasma. The influence
      of tri-sodium citrate (TSC) on release behaviour was investigated through in
      vitro dissolution and in vivo absorption. Linear and nonlinear (quadratic, cubic,
      sigmoid functions) deconvolution based in vitro-in vivo correlation (IVIVC)
      models were developed using in vitro dissolution data and bioavailability
      profile. Prediction errors were investigated for Cmax and AUC in the light of US
      FDA guidelines for average percent prediction error. Release rate indicated that
      TSC was directly proportional to its concentration in the formulation. In vitro
      optimized formulation showed nearly 4.5h lag time and 5.24 +/- 1.74% drug
      releases in initial 4.5h following rapid release 97.11 +/- 1.87% in 6h. The
      deconvolution based IVIVC model appeared to be curvilinear for all three
      pulsatile formulations. Among various functions investigated the model using
      cubic function showed a better correlation (r>0.99) and satisfies the US FDA
      guidelines for average percent prediction error of less than 10%.

PMID- 24565900
TI  - Complexation of sodium caseinate with gum tragacanth: Effect of various species
      and rheology of coacervates.
AB  - We investigated complex coacervation of sodium caseinate/Astragalus rahensis
      (A.r) as a function of pH with light scattering, spectrophotometry, and viscosity
      measurements. Interestingly, sodium caseinate/A.r displayed five structural
      transitions; pH 7.00 to pH ~5.40: no interaction occurred, pH ~5.40 to pH ~4.80:
      initiation of the formation of primary soluble complexes, pH ~4.80 to ~4.30:
      formation of interpolymer complexes, pH ~4.30 to ~4.02: optimum coacervation and
      pH ~4.02 to ~2.50: suppression of coacervation. In addition, rheological
      properties of sodium caseinate/A.r coacervates were studied at various pH values.
      A much higher storage modulus (G') than loss modulus (G") for all sodium
      caseinate/A.r coacervates suggests the formation of highly interconnected gel
      like network structures with mainly elastic behaviour. Moreover, sodium
      caseinate/A.r coacervates at all pH values exhibited a shear thinning behaviour
      across the entire shear rate range investigated. Effects of different species of
      gum tragacanth on the interactions with sodium caseinate have been scarcely
      studied. Our study showed that systems containing various species (A.r, soluble
      fraction of A.r and Astragalus gossypinus (A.g)) had different critical pH values
      and particle sizes during complex coacervation, which could be due to different
      ratio of soluble to insoluble fractions and uronic acid content of various
      species. 

PMID- 24565901
TI  - Is presence of nuchal umbilical cord an indication for cesarean delivery?

PMID- 24565902
TI  - More children are being treated on adult psychiatric wards, investigation shows.

PMID- 24565903
TI  - IL-1 and TNF-alpha regulation of aryl hydrocarbon receptor (AhR) expression in
      HSY human salivary cells.
AB  - OBJECTIVES: Recent findings demonstrate that nuclear receptor - aryl hydrocarbon
      receptor (AhR) may play an important role in the pathogenesis of Sjogren's
      syndrome (SS) via involvement in Epstein-Barr virus reactivation. In that study a
      reporter system was used. Therefore, it was decided to define AhR expression in
      human salivary cell line (HSY) and its functional regulators. DESIGN: The
      expression and functional regulation of AhR was studied in HSY cells. The cells
      were incubated with dioxin (TCDD) - AhR model inducer, IL-1 and TNF-alpha. qRT
      PCR was applied to assess the expression of AHR, AHRR (AhR repressor), ARNT (AhR
      nuclear translocator) as well as AhR dependent genes: CYP1A1 and CYP1B1.
      Enzymatic activity of CYP1A1 and CYP1B1 was evaluated using luciferin-labelled
      CYPs substrate. RESULTS: In general, dioxin did not significantly influence the
      expression of AHR and ARNT, but reduced AHRR level. AhR dependent gene
      expression, i.e. CYP1A1 and CYP1B1 increased gradually with TCDD incubation time.
      TNF-alpha significantly induced AHR along with CYP1A1 and CYP1B1 expression. IL
      1beta did not affect AHR expression, and had minimal effects on CYP1 mRNA levels.
      Exposure of HSY cells to TCDD resulted in time-dependent induction of CYP1A1 and
      CYP1B1 enzymatic activity. CONCLUSIONS: This study documents functional
      expression of AhR in HSY as well as induction of AhR and its dependent genes by
      TNF-alpha.

PMID- 24565904
TI  - The synthesis of 4,7-disubstituted-2H-benzo[b][1,4]-oxazin-3(4H)-ones using
      Smiles rearrangement and their in vitro evaluation as platelet aggregation
      inhibitors.
AB  - A series of novel benzo[b][1,4]oxazin-3(4H)-one derivatives were synthesized as
      platelet aggregation inhibitors for structure-activity relationships (SAR)
      analysis. The synthetic pattern, involved Smiles rearrangement for the
      preparation of benzoxazine, was proven to be more efficient than the conventional
      methods. Biological evaluation demonstrated that among all the synthesized
      compounds, compound 9u (IC50=9.20MUM) exhibited the most potent inhibition
      activity compared with aspirin, the positive control (IC50=7.07MUM). Molecular
      docking revealed that these set of compounds could be the GPIIb/IIIa antagonist
      for that they could be situated in the binding site of GPIIb/IIIa receptor quite
      well. 

PMID- 24565905
TI  - Synthesis and antitumor activities of novel dipeptide derivatives derived from
      dehydroabietic acid.
AB  - A series of dipeptide derivatives from dehydroabietic acid were designed and
      synthesized as novel antitumor agents. The antitumor activities screening
      indicated that many compounds showed moderate to high levels of inhibition
      activities against NCI-H460, HepG2, SK-OV-3, BEL-7404, HeLa and HCT-116 cancer
      cell lines and that some displayed more potent inhibitory activities than
      commercial anticancer drug 5-fluorouracil. The mechanism of representative
      compound 7b was studied by AO/EB staining, Hoechst 33258 staining, JC-1
      mitochondrial membrane potential staining, TUNEL assay, DNA ladder assay and flow
      cytometry, which exhibited that the compound could induce apoptosis in HeLa
      cells. Further investigation showed that compound 7b induced apoptosis of HeLa
      cells through a mitochondrial pathway. 

PMID- 24565906
TI  - Assessment of freestanding membranes prepared from Antheraea pernyi silk fibroin
      as a potential vehicle for corneal epithelial cell transplantation.
AB  - Freestanding membranes created from Bombyx mori silk fibroin (BMSF) offer a
      potential vehicle for corneal cell transplantation since they are transparent and
      support the growth of human corneal epithelial (HCE) cells. Fibroin derived from
      the wild silkworm Antheraea pernyi (APSF) might provide a superior material by
      virtue of containing putative cell-attachment sites that are absent from BMSF.
      Thus we have investigated the feasibility of producing transparent, freestanding
      membranes from APSF and have analysed the behaviour of HCE cells on this
      material. No significant differences in cell numbers or phenotype were observed
      in short term HCE cell cultures established on either fibroin. Production of
      transparent freestanding APSF membranes, however, proved to be problematic as
      cast solutions of APSF were more prone to becoming opaque, displayed
      significantly lower permeability and were more brittle than BMSF-membranes.
      Cultures of HCE cells established on either membrane developed a normal
      stratified morphology with cytokeratin pair 3/12 being immuno-localized to the
      superficial layers. We conclude that while it is feasible to produce transparent
      freestanding membranes from APSF, the technical difficulties associated with this
      biomaterial, along with an absence of enhanced cell growth, currently favour the
      continued development of BMSF as a preferred vehicle for corneal cell
      transplantation. Nevertheless, it remains possible that refinement of techniques
      for processing APSF might yet lead to improvements in the handling properties and
      performance of this material. 

PMID- 24565908
TI  - Novel action modality of the diterpenoid anisomelic acid causes depletion of E6
      and E7 viral oncoproteins in HPV-transformed cervical carcinoma cells.
AB  - Cervical cancer, the second most common malignancy among women, is mainly caused
      by human papilloma virus (HPV) infection. In HPV-positive cervical cancer cells,
      the activity of p53 and the induction of p21 are inhibited by the HPV
      oncoproteins E6 and E7. Therefore, blocking the activity of E6 and E7 would serve
      as an important therapeutic target in these cancer cells. In this study,
      anisomelic acid (AA), a natural compound belonging to the same diterpenoid family
      of bioactive compounds as taxol, was found to deplete the E6 and E7 proteins in
      HPV-positive cervical cancer cells. Consequently, p53 and the p53-responsive
      gene, p21, were dramatically induced, leading to G2/M-phase cell cycle arrest. AA
      mediated cell cycle arrest and p21 expression were canceled when p53 was down
      regulated by p53-shRNA. AA also induced p53-independent intrinsic apoptosis by
      depletion of the cellular inhibitor of apoptosis protein 2 (cIAP2) whose
      proteosomal degradation is inhibited by E6. The in ovo chick embryo
      chorioallantoic membrane (CAM) assay showed that anisomelic acid inhibited the
      tumor growth of the cervical cancer SiHa cells. AA is revealed to hold a novel
      action modality based on specific targeting of the HPV oncoproteins, which
      restores p53-mediated growth arrest and induces apoptosis by terminating E6
      mediated cIAP2 stabilization. 

PMID- 24565907
TI  - The potential of heparanase as a therapeutic target in cancer.
AB  - Heparanase has generated substantial interest as therapeutic target for antitumor
      therapy, because its activity is implicated in malignant behavior of cancer cells
      and in tumor progression. Increased heparanase expression was found in numerous
      tumor types and correlates with poor prognosis. Heparanase, an endoglucuronidase
      responsible for heparan sulfate cleavage, regulates the structure and function of
      heparan sulfate proteoglycans, leading to disassembly of the extracellular
      matrix. The action of heparanase is involved in multiple regulatory events
      related, among other effects, to augmented bioavailability of growth factors and
      cytokines. Inhibitors of heparanase suppress tumor growth, angiogenesis and
      metastasis by modulating growth factor-mediated signaling, ECM barrier function
      and cell interactions in the tumor microenvironment. Therefore, targeting
      heparanase has potential implications for anti-tumor, anti-angiogenic and anti
      inflammatory therapies. Current approaches for heparanase inhibition include
      development of chemically modified heparins, small molecule inhibitors and
      neutralizing antibodies. The available evidence supports the emerging utility of
      heparanase inhibition as a promising antitumor strategy, specifically in rational
      combination with other agents. The recent studies with compounds designed to
      block heparanase (e.g., modified heparins) provide a rational basis for their
      therapeutic application and optimization. 

PMID- 24565909
TI  - Discovery of 3-(4-hydroxybenzyl)-1-(thiophen-2-yl)chromeno[2,3-c]pyrrol-9(2H)-one
      as a phosphodiesterase-5 inhibitor and its complex crystal structure.
AB  - Phosphodiesterase-5 (PDE5) inhibitors have been approved for the treatment of
      erectile dysfunction and pulmonary hypertension, but enthusiasm on discovery of
      PDE5 inhibitors continues for their potential new applications. Reported here is
      discovery of a series of new PDE5 inhibitors by structure-based design, molecular
      docking, chemical synthesis, and enzymatic characterization. The best compound, 3
      (4-hydroxybenzyl)-1-(thiophen-2-yl)chromeno[2,3-c]pyrrol-9(2H)-one (57), has an
      IC50 of 17 nM against the PDE5 catalytic domain and good selectivity over other
      PDE families. The crystal structure of the PDE5 catalytic domain in complex with
      57 was determined at 2A resolution and showed that 57 occupies the same pocket as
      other PDE5 inhibitors, but has a different binding pattern in detail. On the
      basis of the binding pattern of 57, a novel scaffold can be proposed as a
      candidate of PDE inhibitors.

PMID- 24565911
TI  - Development of a modified sampling and calculation method for isotope plasma
      clearance assessment of the glomerular filtration rate in patients with cirrhosis
      and ascites.

PMID- 24565912
TI  - Response to the letter about 'Development of a modified sampling and calculation
      method for isotope plasma clearance assessment of glomerular filtration rate in
      patients with cirrhosis and ascites'.

PMID- 24565910
TI  - Telatinib reverses chemotherapeutic multidrug resistance mediated by ABCG2 efflux
      transporter in vitro and in vivo.
AB  - Multidrug resistance (MDR) is a phenomenon where cancer cells become
      simultaneously resistant to anticancer drugs with different structures and
      mechanisms of action. MDR has been shown to be associated with overexpression of
      ATP-binding cassette (ABC) transporters. Here, we report that telatinib, a small
      molecule tyrosine kinase inhibitor, enhances the anticancer activity of ABCG2
      substrate anticancer drugs by inhibiting ABCG2 efflux transporter activity. Co
      incubation of ABCG2-overexpressing drug resistant cell lines with telatinib and
      ABCG2 substrate anticancer drugs significantly reduced cellular viability,
      whereas telatinib alone did not significantly affect drug sensitive and drug
      resistant cell lines. Telatinib at 1 MUM did not significantly alter the
      expression of ABCG2 in ABCG2-overexpressing cell lines. Telatinib at 1 MUM
      significantly enhanced the intracellular accumulation of [(3)H]-mitoxantrone (MX)
      in ABCG2-overexpressing cell lines. In addition, telatinib at 1 MUM significantly
      reduced the rate of [(3)H]-MX efflux from ABCG2-overexpressing cells.
      Furthermore, telatinib significantly inhibited ABCG2-mediated transport of [(3)H]
      E217betaG in ABCG2 overexpressing membrane vesicles. Telatinib stimulated the
      ATPase activity of ABCG2 in a concentration-dependent manner, indicating that
      telatinib might be a substrate of ABCG2. Binding interactions of telatinib were
      found to be in transmembrane region of homology modeled human ABCG2. In addition,
      telatinib (15 mg/kg) with doxorubicin (1.8 mg/kg) significantly decreased the
      growth rate and tumor size of ABCG2 overexpressing tumors in a xenograft nude
      mouse model. These results, provided that they can be translated to humans,
      suggesting that telatinib, in combination with specific ABCG2 substrate drugs may
      be useful in treating tumors that overexpress ABCG2.

PMID- 24565914
TI  - Anatomical study of the ligamentous attachments and articular surfaces of the
      trapeziometacarpal joint. Consequences on surgical management of its
      osteoarthrosis.
AB  - In the goal to optimize conservative surgical techniques of the
      trapeziometacarpal joint in cases of moderate osteoarthritis, we have defined the
      relationships between the ligamentous attachments and the articular surfaces onto
      the trapezium and the first metacarpal bone on the one hand, and the dorsovolar
      and the transverse diameters of the articular surfaces on the other hand. Thirty
      six trapeziometacarpal joints (from 18 fresh cadavers) were studied. They were
      separated into two groups depending on the macroscopic assessment of chondral
      disease. Group A included stages I to III (no osteoarthritis or moderate
      osteoarthritis), group B included stages IV (major cartilage destruction). The
      dorsovolar and transverse sizes of the articular surfaces were measured.
      Dorsoradial ligament (DRL), posterior oblique ligament (POL), intermetacarpal
      ligament (IML), ulnar collateral ligament (UCL) and anterior oblique ligament
      (AOL) were dissected and the distance between their attachments and the articular
      surfaces were measured. Group A included 17 joints (71% males) and group B
      included 19 joints (95% females). For the first metacarpal bone, the average
      ratio between the dorsovolar diameter and the transverse diameter of metacarpal
      articular surfaces was significantly higher in group B and the average distance
      between the ligamentous attachments and the articular surface was more than two
      millimeters, except for the DRL in group B. For the trapezium, only the posterior
      ligaments (DRL and POL) of group A were inserted at a mean distance more than two
      millimeters from the articular surfaces. Dorsovolar length of the metacarpal
      articular surface was higher for osteoarthritis cases. This difference can be
      explained by the existence of a palmar osteophyte that was always found in stage
      IV. Describing a map of the ligamentous attachment distance from the articular
      surface could help surgeons to avoid the ligamentous injury during minimal
      osteochondral resection. 

PMID- 24565915
TI  - Polymer optoelectronic structures for retinal prosthesis.
AB  - This commentary highlights the effectiveness of optoelectronic properties of
      polymer semiconductors based on recent results emerging from our laboratory,
      where these materials are explored as artificial receptors for interfacing with
      the visual systems. Organic semiconductors based polymer layers in contact with
      physiological media exhibit interesting photophysical features, which mimic
      certain natural photoreceptors, including those in the retina. The availability
      of such optoelectronic materials opens up a gateway to utilize these structures
      as neuronal interfaces for stimulating retinal ganglion cells. In a recently
      reported work entitled "A polymer optoelectronic interface provides visual cues
      to a blind retina," we utilized a specific configuration of a polymer
      semiconductor device structure to elicit neuronal activity in a blind retina upon
      photoexcitation. The elicited neuronal signals were found to have several
      features that followed the optoelectronic response of the polymer film. More
      importantly, the polymer-induced retinal response resembled the natural response
      of the retina to photoexcitation. These observations open up a promising material
      alternative for artificial retina applications. 

PMID- 24565916
TI  - Intra-muscular location in soft tissue sarcomas: impact on oncologic outcome.
AB  - BACKGROUND: Soft tissue sarcoma (STS) of intra-muscular location is confined
      within well-defined barrier, amenable to easier surgical resection. It is
      generally assumed that STS of intra-muscular location would have favorable
      outcomes compared to those of inter-muscular location. However, no clear evidence
      on this assumption can be found. This study examined if intra-muscular location
      of STS would have favorable effect on oncologic outcomes. METHODS: Among the 161
      patients treated for previously untreated, non-metastatic and deep-seated STS,
      extra-compartmental tumors (65) or tumors that spread beyond the muscle of origin
      (23) were excluded. Remaining 73 patients were classified into two groups
      according to tumor location; intra-muscular group (confined within muscle of
      origin, n = 32) and inter-muscular group (located between muscles, n = 41).
      RESULTS: Two patients (6.3%) in intra-muscular group developed local recurrence
      whereas 10 patients (24.3%) developed local recurrence in inter-muscular group (p
      = 0.056). Patients in intra-muscular group showed significantly better local
      recurrence-free survival than those in inter-muscular group (p = 0.029). However,
      there was no significant difference in development of metastasis (p = 0.143) nor
      disease-specific survival (p = 0.106). CONCLUSIONS: Our study indicates that STS
      of intra-muscular location is associated with better local control. Whether this
      advantage is due to its biological property or surgical resectability remains to
      be elucidated.

PMID- 24565917
TI  - Autophagy in the endocrine glands.
AB  - Autophagy is an important cellular process involving the degradation of
      intracellular components. Its regulation is complex and while there are many
      methods available, there is currently no single effective way of detecting and
      monitoring autophagy. It has several cellular functions that are conserved
      throughout the body, as well as a variety of different physiological roles
      depending on the context of its occurrence in the body. Autophagy is also
      involved in the pathology of a wide range of diseases. Within the endocrine
      system, autophagy has both its traditional conserved functions and specific
      functions. In the endocrine glands, autophagy plays a critical role in
      controlling intracellular hormone levels. In peptide-secreting cells of glands
      such as the pituitary gland, crinophagy, a specific form of autophagy, targets
      the secretory granules to control the levels of stored hormone. In steroid
      secreting cells of glands such as the testes and adrenal gland, autophagy targets
      the steroid-producing organelles. The dysregulation of autophagy in the endocrine
      glands leads to several different endocrine diseases such as diabetes and
      infertility. This review aims to clarify the known roles of autophagy in the
      physiology of the endocrine system, as well as in various endocrine diseases. 

PMID- 24565918
TI  - Scar-free wound healing and regeneration in amphibians: immunological influences
      on regenerative success.
AB  - Salamanders and frogs are distinct orders of Amphibians with very different
      immune systems during adult life, exhibiting varying potential for scar free
      repair and regeneration. While salamanders can regenerate a range of body parts
      throughout all stages of life, regeneration is restricted to early stages of frog
      development. Comparison of these two closely related amphibian orders provides
      insights into the immunological influences on wound repair, and the different
      strategies that have evolved either to limit infection or to facilitate efficient
      regeneration. After injury, cells of the immune system are responsible for the
      removal of damaged cells and providing a cohort of important growth factors and
      signaling molecules. Immune cells not only regulate new vessel growth important
      for supplying essential nutrients to damaged tissue but, modulate the
      extracellular matrix environment by regulating fibroblasts and the scarring
      response. The profile of immune cell infiltration and their interaction with
      local tissue immune cells directly influences many aspects of the wound healing
      outcomes and can facilitate or prevent regeneration. Evidence is emerging that
      the transition from wound healing to regeneration is reliant on immune cell
      engagement and that the success of regeneration in amphibians may depend on
      complex interactions between stem cell progenitors and immune cell subsets. The
      potential immunological barriers to mammalian regeneration are discussed with
      implications for the successful delivery of stem cell therapeutic strategies in
      patients. 

PMID- 24565920
TI  - How does protein misfolding in the endoplasmic reticulum affect lipid metabolism
      in the liver?
AB  - PURPOSE OF REVIEW: The endoplasmic reticulum (ER) maintains cellular metabolic
      homeostasis by coordinating protein synthesis, secretion activities, lipid
      biosynthesis and calcium (Ca2+) storage. In this review, we will discuss how
      altered ER homeostasis contributes to dysregulation of hepatic lipid metabolism
      and contributes to liver-associated metabolic diseases. RECENT FINDINGS:
      Perturbed ER functions or accumulation of unfolded protein in the ER leads to the
      activation of the unfolded protein response (UPR) to protect the cell from ER
      stress. Recent findings pinpoint the key regulatory role of the UPR in hepatic
      lipid metabolism and demonstrate the potential causal mechanism of ER stress in
      metabolic dysregulation including diabetes and obesity. SUMMARY: A wide range of
      factors can alter the protein-folding environment in the ER of hepatocytes and
      contribute to dysregulation of hepatic lipid metabolism and liver disease. The
      UPR constitutes a series of adaptive programs that preserve ER protein-folding
      environment and maintain hepatic lipid homeostasis. Signaling components of the
      UPR are emerging as potential targets for intervention and treatment of human
      liver-associated metabolic diseases.

PMID- 24565922
TI  - Programmed necrosis in microbial pathogenesis.
AB  - Programmed cell death is an important facet of host-pathogen interactions.
      Although apoptosis has long been implicated as the major form of programmed cell
      death in host defense, the past decade has seen the emergence of other forms of
      regulated death, including programmed necrosis. While the molecular mechanisms of
      programmed necrosis continue to be unveiled, an increasing number of viral and
      bacterial pathogens induce this form of death in host cells, with important
      consequences for infection, control, and pathogenesis. Moreover, pathogen
      strategies to manipulate or utilize this pathway are now being discovered. In
      this review, we focus on a variety of viral and bacterial pathogens where a role
      for programmed necrosis is starting to be appreciated. In particular, we focus on
      the mechanistic details of how the host or the pathogen might appropriate this
      pathway for its own benefit. 

PMID- 24565921
TI  - Comparative gene identification-58/alpha/beta hydrolase domain 5: more than just
      an adipose triglyceride lipase activator?
AB  - PURPOSE OF REVIEW: Comparative gene identification-58 (CGI-58) is a lipid droplet
      associated protein that controls intracellular triglyceride levels by its ability
      to activate adipose triglyceride lipase (ATGL). Additionally, CGI-58 was
      described to exhibit lysophosphatidic acid acyl transferase (LPAAT) activity.
      This review focuses on the significance of CGI-58 in energy metabolism in adipose
      and nonadipose tissue. RECENT FINDINGS: Recent studies with transgenic and CGI-58
      deficient mouse strains underscored the importance of CGI-58 as a regulator of
      intracellular energy homeostasis by modulating ATGL-driven triglyceride
      hydrolysis. In accordance with this function, mice and humans that lack CGI-58
      accumulate triglyceride in multiple tissues. Additionally, CGI-58-deficient mice
      develop an ATGL-independent severe skin barrier defect and die soon after birth.
      Although the premature death prevented a phenotypical characterization of adult
      global CGI-58 knockout mice, the characterization of mice with tissue-specific
      CGI-58 deficiency revealed new insights into its role in neutral lipid and energy
      metabolism. Concerning the ATGL-independent function of CGI-58, a recently
      identified LPAAT activity for CGI-58 was shown to be involved in the generation
      of signaling molecules regulating inflammatory processes and insulin action.
      SUMMARY: Although the function of CGI-58 in the catabolism of cellular
      triglyceride depots via ATGL is well established, further studies are required to
      consolidate the function of CGI-58 as LPAAT and to clarify the involvement of CGI
      58 in the metabolism of skin lipids.

PMID- 24565923
TI  - Supramodal processing optimizes visual perceptual learning and plasticity.
AB  - Multisensory interactions are ubiquitous in cortex and it has been suggested that
      sensory cortices may be supramodal i.e. capable of functional selectivity
      irrespective of the sensory modality of inputs (Pascual-Leone and Hamilton, 2001;
      Renier et al., 2013; Ricciardi and Pietrini, 2011; Voss and Zatorre, 2012). Here,
      we asked whether learning to discriminate visual coherence could benefit from
      supramodal processing. To this end, three groups of participants were briefly
      trained to discriminate which of a red or green intermixed population of random
      dot-kinematograms (RDKs) was most coherent in a visual display while being
      recorded with magnetoencephalography (MEG). During training, participants heard
      no sound (V), congruent acoustic textures (AV) or auditory noise (AVn);
      importantly, congruent acoustic textures shared the temporal statistics - i.e.
      coherence - of visual RDKs. After training, the AV group significantly
      outperformed participants trained in V and AVn although they were not aware of
      their progress. In pre- and post-training blocks, all participants were tested
      without sound and with the same set of RDKs. When contrasting MEG data collected
      in these experimental blocks, selective differences were observed in the dynamic
      pattern and the cortical loci responsive to visual RDKs. First and common to all
      three groups, vlPFC showed selectivity to the learned coherence levels whereas
      selectivity in visual motion area hMT+ was only seen for the AV group. Second and
      solely for the AV group, activity in multisensory cortices (mSTS, pSTS)
      correlated with post-training performances; additionally, the latencies of these
      effects suggested feedback from vlPFC to hMT+ possibly mediated by temporal
      cortices in AV and AVn groups. Altogether, we interpret our results in the
      context of the Reverse Hierarchy Theory of learning (Ahissar and Hochstein, 2004)
      in which supramodal processing optimizes visual perceptual learning by
      capitalizing on sensory-invariant representations - here, global coherence levels
      across sensory modalities.

PMID- 24565924
TI  - Cross-reactive antibody responses to the novel avian influenza A H7N9 virus in
      Shanghai adults.

PMID- 24565925
TI  - Testosterone enhances functional recovery after stroke through promotion of
      antioxidant defenses, BDNF levels and neurogenesis in male rats.
AB  - It is reported that circulating testosterone levels decrease after cerebral
      ischemia. The aim of this study was to evaluate the effects of testosterone on
      oxidative stress, brain-derived neurotrophic factor (BDNF) levels, neurogenesis,
      histological damage and sensorimotor recovery in a castrated male rat model of
      focal cerebral ischemia. Animals were divided into four groups. For all animals,
      castrations were conducted 7 days before transient middle cerebral artery
      occlusion (MCAO) was done and cerebral ischemia was induced. The first group
      served as sham. Second was MCAO group and received vehicle only, third was MCAO
      group that was post-treated with testosterone and the fourth was MCAO group post
      treated with testosterone and flutamide. Treatment only with testosterone
      significantly weakened oxidative stress and increased BDNF levels and
      sensorimotor recovery during a 10 days period. Rats receiving testosterone
      demonstrated a significant reduction in infarct volume and a significant increase
      in neurogenesis on 10th day after focal cerebral ischemia. Our results for the
      first time showed a potential advantageous effect of testosterone after cerebral
      ischemia in male rats, which was probably mediated by promoting antioxidant
      defenses, BDNF levels and neurogenesis. 

PMID- 24565926
TI  - Functional organization of intrinsic connectivity networks in Chinese-chess
      experts.
AB  - The functional architecture of the human brain has been extensively described in
      terms of functional connectivity networks, detected from the low-frequency
      coherent neuronal fluctuations during a resting state condition. Accumulating
      evidence suggests that the overall organization of functional connectivity
      networks is associated with individual differences in cognitive performance and
      prior experience. Such an association raises the question of how cognitive
      expertise exerts an influence on the topological properties of large-scale
      functional networks. To address this question, we examined the overall
      organization of brain functional networks in 20 grandmaster and master level
      Chinese-chess players (GM/M) and twenty novice players, by means of resting-state
      functional connectivity and graph theoretical analyses. We found that, relative
      to novices, functional connectivity was increased in GM/Ms between basal ganglia,
      thalamus, hippocampus, and several parietal and temporal areas, suggesting the
      influence of cognitive expertise on intrinsic connectivity networks associated
      with learning and memory. Furthermore, we observed economical small-world
      topology in the whole-brain functional connectivity networks in both groups, but
      GM/Ms exhibited significantly increased values of normalized clustering
      coefficient which resulted in increased small-world topology. These findings
      suggest an association between the functional organization of brain networks and
      individual differences in cognitive expertise, which might provide further
      evidence of the mechanisms underlying expert behavior. 

PMID- 24565927
TI  - Umbilical cord blood cells regulate the differentiation of endogenous neural stem
      cells in hypoxic ischemic neonatal rats via the hedgehog signaling pathway.
AB  - Transplantation of umbilical cord blood mononuclear cells (UCBMC) promotes the
      proliferation of endogenous neural stem cells (NSCs), but it has been unclear
      whether the proliferating NSCs can differentiate into mature neural cells.
      Therefore, we explored the effects of UCBMC transplantation on the
      differentiation of endogenous NSCs and their underlying mechanisms. Seven-day-old
      Sprague-Dawley rats underwent left carotid ligation followed by hypoxic stress.
      UCBMC were transplanted 24h after hypoxia ischemia (HI). BrdU/beta
      tubulin/HNA/DAPI, BrdU/GFAP/HNA/DAPI, Ngn1/DAPI, and BMP4/DAPI were measured by
      immunofluorescence staining; Shh, Gli1, Ngn1, and BMP4 proteins were measured by
      western-blot analysis 28 days after transplantation. More newborn neurons and
      fewer astrocytes were observed in the HI+UCBMC group, its neuronal percentage was
      higher, and glial percentage was lower compared with the N+UCBMC (P<0.05) and
      HI+PBS groups (P<0.01), while fewer newborn neurons and more newborn astrocytes
      were found in the HI+cyclopamine (an antagonist of the hedgehog protein)+UCBMC
      group compared with the HI+UCBMC group (P<0.01). The expression of Shh, Gli1, and
      Ngn1 proteins was higher and BMP4 protein was lower in the HI+UCBMC compared with
      the HI+PBS group (P<0.01) and the HI+cyclopamine+UCBMC group (P<0.01). Linear
      regression analysis showed that the differentiation of NSCs correlated with
      expression of Ngn1 and BMP4 proteins (P<0.01). In conclusion, UCBMC promote
      neuronal differentiation and reduce glial differentiation in hypoxic ischemic
      neonatal rats via the hedgehog signaling pathway. 

PMID- 24565929
TI  - A functionalized phosphonate-rich organosilica layered hybrid material (PSLM)
      fabricated through a mild process for heavy metal uptake.
AB  - A phosphonate-rich organosilica layered hybrid material (PSLM) made of 3
      (trihydroxysilyl)propyl methylphosphonate, monosodium salt, as the single silica
      source, has been obtained from its aqueous solution through a xerogel process and
      mild thermal aging. The method is simple, affording bulk quantities of powdered
      PSLM in a single-step. The hybrid is stable in water and possesses a high content
      of phosphonate groups fixed on the solid matrix. In addition, PSLM shows good
      thermal stability, which exceeds 300 degrees C in air. The material was
      characterized using SEM, TEM, XRD, FT-IR and TGA techniques. Potentiometric
      titrations show that PSLM bears high-surface density of phosphonate groups (3
      mmol g(-1)). As a result, the material displays high metal uptake capacity for
      heavy metal ions such as Cu(2+) (2.72mmolg(-1)), Pb(2+) (1.67 mmol g(-1)) and
      Cd(2+) (1.00 mmol g(-1)) at neutral pH values e.g. the pH of natural waters.
      Detailed theoretical modeling using a Surface Complexation Model combined with
      Electron Paramagnetic Resonance (EPR) spectroscopy shows that the surface
      distribution of surface bound Cu(2+) ions is rather homogeneous e.g. copper
      binding phosphonate sites are arranged in average distances 5-8A.

PMID- 24565930
TI  - Quality and generation rate of solid residues in the boiler of a waste-to-energy
      plant.
AB  - The Danish waste management system relies significantly on waste-to-energy (WtE)
      plants. The ash produced at the energy recovery section (boiler ash) is
      classified as hazardous waste, and is commonly mixed with fly ash and air
      pollution control residues before disposal. In this study, a detailed
      characterization of boiler ash from a Danish grate-based mass burn type WtE was
      performed, to evaluate the potential for improving ash management. Samples were
      collected at 10 different points along the boiler's convective part, and analysed
      for grain size distribution, content of inorganic elements, polychlorinated
      dibenzo-p-dioxins and dibenzofurans (PCDD and PCDF), and leaching of metals. For
      all samples, PCDD and PCDF levels were below regulatory limits, while high pH
      values and leaching of e.g. Cl were critical. No significant differences were
      found between boiler ash from individual sections of the boiler, in terms of
      total content and leaching, indicating that separate management of individual ash
      fractions may not provide significant benefits. 

PMID- 24565931
TI  - Cultivation of Nannochloropsis salina in municipal wastewater or digester
      centrate.
AB  - Meaningful use of biofuels for transportation depends on utilization of water
      from non-traditional, non-potable resources. Here it is hypothesized that (i)
      reclaimed wastewater or nutrient-rich side streams derived from municipal
      wastewater treatment are suitable for that purpose and (ii) use of those waters
      for algal growth can promote water quality through nutrient management.
      Experiments showed that metals levels in municipal wastewaters are unlikely to
      inhibit algal growth and lipid production, at least by metals tolerant microalgae
      like Nannochloropsis salina. Cells grew without inhibition in treated municipal
      wastewater or centrate derived from wastewater treatment at additions up to 75
      percent v/v in their normal growth medium minus nitrogen and phosphorus. Although
      wastewater provides a suitable nutrient source for algal growth, not enough
      municipal wastewater is available to support a meaningful biofuels industry
      without efficient water recycling and nutrient recovery/reuse from spent algae. 

PMID- 24565932
TI  - An arabinogalactan from flowers of Chrysanthemum morifolium: structural and
      bioactivity studies.
AB  - A water-soluble polysaccharide (P2) with a molecular weight of 1.7*10(5)Da was
      isolated from the hot aqueous extract of flowers of the Chrysanthemum morifolium.
      It was homogeneous for there was only a symmetrical peak on the spectrum of high
      performance gel permeation chromatography. Monosaccharide analysis revealed that
      P2 is an arabinogalactan containing arabinose (38.4% w/w), galactose (58.8% w/w),
      and glucose (2.8% w/w) in a ratio of 1:1.53:0.07. The GC-MS results of the
      derived alditol acetates from the permethylated P2 showed some separate peaks
      corresponding to (1->6)-linked Gal, (1->3,6)-linked Gal, terminal Ara, (1->5)
      linked Ara, and (1->3,5)-linked Ara units in a molar ratio of nearly
      1.12:1.90:1.84:0.35:0.12. Terminal Glc unit also existed in a trace amount. (1)H,
      (13)C, DEPT-135 and 2D NMR (including HMQC and HMBC), as well as graded acid
      hydrolysis experiment, indicated that the core structure features include a
      backbone chain consisting of (1->6)-linked and (1->3,6)-linked Galp residues.
      Side chains which were composed of terminal Glcp, terminal, (1->5)-linked and (1
      >3,5)-linked Araf residues were located at position 3. Additionally, P2 showed
      good immunological activity as it significantly enhanced splenocyte proliferation
      in relatively low 25 and 50MUg/mL doses. However, P2 showed little effects of
      thymocyte proliferation, indicating that it may have two modes of action. 

PMID- 24565928
TI  - Spatio-temporal processing of words and nonwords: hemispheric laterality and
      acute alcohol intoxication.
AB  - This study examined neurofunctional correlates of reading by modulating semantic,
      lexical, and orthographic attributes of letter strings. It compared the spatio
      temporal activity patterns elicited by real words (RW), pseudowords,
      orthographically regular, pronounceable nonwords (PN) that carry no meaning, and
      orthographically illegal, nonpronounceable nonwords (NN). A double-duty lexical
      decision paradigm instructed participants to detect RW while ignoring nonwords
      and to additionally respond to words that refer to animals (AW). Healthy social
      drinkers (N=22) participated in both alcohol (0.6 g/kg ethanol for men, 0.55 g/kg
      for women) and placebo conditions in a counterbalanced design. Whole-head MEG
      signals were analyzed with an anatomically-constrained MEG method. Simultaneously
      acquired ERPs confirm previous evidence. Spatio-temporal MEG estimates to RW and
      PN are consistent with the highly replicable left-lateralized ventral visual
      processing stream. However, the PN elicit weaker activity than other stimuli
      starting at ~230 ms and extending to the M400 (magnetic equivalent of N400) in
      the left lateral temporal area, indicating their reduced access to lexicosemantic
      stores. In contrast, the NN uniquely engage the right hemisphere during the M400.
      Increased demands on lexicosemantic access imposed by AW result in greater
      activity in the left temporal cortex starting at ~230 ms and persisting through
      the M400 and response preparation stages. Alcohol intoxication strongly
      attenuates early visual responses occipito-temporally overall. Subsequently,
      alcohol selectively affects the left prefrontal cortex as a function of
      orthographic and semantic dimensions, suggesting that it modulates the dynamics
      of the lexicosemantic processing in a top-down manner, by increasing difficulty
      of semantic retrieval.

PMID- 24565934
TI  - [Multicentric prospective randomized study evaluating the interest of
      intravaginal electro-stimulation at home for urinary incontinence after prior
      perineal reeducation. Interim analysis].
AB  - OBJECTIVES: Perineal reeducation of stress urinary incontinence is beneficial in
      80% of cases. However, patients have to perform self-retraining exercises of the
      perineal muscles at home, in order to maintain the benefit of the physiotherapy.
      The aim of this study is to assess the benefit of GYNEFFIK((r)), a perineal
      electro-stimulator, during this home-care phase. PATIENTS AND METHODS: Women with
      stress urinary incontinence (UI) or with mixed UI (composed predominantly of
      stress UI) that responded to physiotherapy were included in this study in two
      parallel groups. The groups followed a self-reeducation program, with or without
      GYNEFFIK((r)) electro-stimulation sessions. The comparison of the two groups was
      based on the rate of women for whom the benefit of the initial perineal
      reeducation was maintained (defined as non-worsening ICIQ and Ditrovie scales'
      score). RESULTS: According to the protocol, an interim analysis was performed on
      95 patients (i.e. almost half of the expected sample size) who had had at least
      one evaluation under treatment, among which 44 patients had finished the study.
      The therapeutic benefit of the initial perineal reeducation was maintained in
      87.8% of the GYNEFFIK((r)) patient group, while it was maintained in 52.2%
      (P=0.0001) in the usual care group (i.e. who did not use electro-stimulation).
      DISCUSSION AND CONCLUSION: Likewise, patient had a more favorable subjective
      impression when using GYNEFFIK((r)) (83.7% versus 60.0% in the usual care group)
      as they felt that they improved during the study. In the GYNEFFIK((r)) group, no
      increase in symptoms was reported, whereas almost one out of five patients in the
      usual care group felt that their condition had worsened.

PMID- 24565935
TI  - [J. Boujenah and P. Madelenat in reply to Demers et al].

PMID- 24565933
TI  - Early life stress disrupts social behavior and prefrontal cortex parvalbumin
      interneurons at an earlier time-point in females than in males.
AB  - Early life stress exposure (ELS) yields risk for psychiatric disorders that might
      occur though a population-specific mechanism that impacts prefrontal cortical
      development. Sex differences in ELS effects are largely unknown and are also
      essential to understand social and cognitive development. ELS can cause
      dysfunction within parvalbumin (PVB)-containing inhibitory interneurons in the
      prefrontal cortex and in several prefrontal cortex-mediated behaviors including
      social interaction. Social behavior deficits are often the earliest observed
      changes in psychiatric disorders, therefore the time-course and causation of
      social interaction deficits after ELS are important to determine. PVB interneuron
      dysfunction can disrupt social behavior, and has been correlated in males with
      elevated markers of oxidative stress and inflammation, such as cyclooxygenase-2
      after ELS. Here, we measured the effects of maternal separation ELS on social
      interaction behaviors in males and females. Prefrontal cortex PVB and
      cyclooxygenase-2 were also measured in juveniles and adolescents using Western
      blots. ELS led to social interaction alterations earlier in females than males.
      Sexually dimorphic behavioral changes were consistent with prefrontal cortex PVB
      loss after ELS. PVB levels were decreased in ELS-exposed juvenile females, while
      males exposed to ELS do not display parvalbumin decreases until adolescence.
      Early behavioral and PVB changes in females did not appear to be mediated through
      cyclooxygenase-2, since levels were not affected in ELS females. Therefore, these
      data suggest that ELS affects males and females differently and with distinct
      developmental profiles. 

PMID- 24565936
TI  - The impact of human activities on land use and land cover changes and
      environmental processes in the Gorce Mountains (Western Polish Carpathians) in
      the past 50 years.
AB  - The role of human impact on the natural environment was studied in the Jaszcze
      and Jamne catchments in the Gorce Mountains (Western Polish Carpathians).
      Analysis of land use and land cover changes using GIS techniques and cartographic
      materials between 1954 and 2004 indicates an increase in forest area by 11.5% and
      18.5%, respectively, at the expense of arable land and grassland areas.
      Agricultural abandonment often occurred on steep slopes (above 10 degrees ) with
      skeletal (shallow) soils at higher elevations (above 800 m a.s.l.). In addition,
      the density of dirt roads decreased from 6.97 km/km(2) in 1981 to 4.3 km/km(2) in
      2008. In former agricultural areas, long expanses of terraces have either
      disappeared or experienced shallow mass movements. The statistical reports and
      questionnaire survey indicate reduced income from farm activities in this region.
      As a result of LULC changes and stream transformation, the Jaszcze and Jamne
      stream channels were shortened, straightened, and narrowed, with tendency to
      incision estimated at 1 cm per year over the past 40 years. The changes observed
      in the environment under human impact, accelerated following 1989, are
      representative of the Western Polish Carpathians.

PMID- 24565937
TI  - Woman with schizophrenia is judged to have mental capacity to decide on
      amputation.

PMID- 24565939
TI  - HARP preferentially co-purifies with RPA bound to DNA-PK and blocks RPA
      phosphorylation.
AB  - The HepA-related protein (HARP/SMARCAL1) is an ATP-dependent annealing helicase
      that is capable of rewinding DNA structures that are stably unwound due to
      binding of the single-stranded DNA (ssDNA)-binding protein Replication Protein A
      (RPA). HARP has been implicated in maintaining genome integrity through its role
      in DNA replication and repair, two processes that generate RPA-coated ssDNA. In
      addition, mutations in HARP cause a rare disease known as Schimke immuno-osseous
      dysplasia. In this study, we purified HARP containing complexes with the goal of
      identifying the predominant factors that stably associate with HARP. We found
      that HARP preferentially interacts with RPA molecules that are bound to the DNA
      dependent protein kinase (DNA-PK). We also found that RPA is phosphorylated by
      DNA-PK in vitro, while the RPA-HARP complexes are not. Our results suggest that,
      in addition to its annealing helicase activity, which eliminates the natural
      binding substrate for RPA, HARP blocks the phosphorylation of RPA by DNA-PK. 

PMID- 24565940
TI  - Measurement and comparison of tibial posterior slope angle in different methods
      based on three-dimensional reconstruction.
AB  - BACKGROUND: The tibial posterior slope (PTS) is an important parameter for
      sagittal alignment which is associated with postoperative range of motion.
      However, the variations of different population subsets and different referential
      axes are still uncertain. METHODS: In this study, 80 healthy people from South
      China were recruited and measured on three-dimensional reconstruction of CT, with
      application of three referential axes, the proximal tibial long axis, the
      anterior and posterior cortices. RESULTS: The averages and standard deviations of
      medial PTS (MPTS) in the three methods were 8.43+/-3.06, 11.45+/-2.82 and 6.31+/
      3.24, separately. The results of lateral PTS (LPTS) were 7.56+/-2.51, 10.17+/
      2.42 and 5.22+/-2.59. There was no significant difference between the male and
      the female, and the two sides of one body. The results of the three axes varied
      but correlated with each other significantly. Through comparison it was found
      that, MPTS/LPTS of people from South China were different from the published data
      of other countries. CONCLUSIONS: Although PTS change markedly according to the
      reference axis, they show significant correlations with each other, and may be
      used safely. There are differences associated with races, but not gender nor the
      two sides of the body. CLINICAL RELEVANCE: The results of the study provided
      references for the reconstruction of the knee PTS, if the differences of
      reference axes, races and genders were considered.

PMID- 24565941
TI  - Brain structural maturation and the foundations of cognitive behavioral
      development.
AB  - PURPOSE OF REVIEW: Thorough knowledge of normal neural foundations for cognitive
      behavioral development is fundamental to understand the mechanisms of both
      neurodevelopmental disorders and normal adaptation. This review aims at
      identifying the trends in MRI studies published within the last 18 months
      illuminating maturational structural brain foundations for normal cognitive
      behavioral development. RECENT FINDINGS: Development is coordinated within
      neurocognitive systems, with predictable functional correlates. There is great
      individual variability within the normal range. Relationships between brain and
      cognitive variance at any given age are moderate, and appear to be of a complex
      and dynamic nature. Importantly, current studies point to a dimensional component
      to cognitive and behavioral psychopathology in which differences among healthy
      and clinical developmental groups exist along a continuum. Finally, factors
      influencing and detectable in early development are likely to have lifespan
      consequences. SUMMARY: Brain development is highly coordinated, but the normal
      individual variation at any given age is substantial. Relationships between brain
      and cognitive measures are typically moderate and may fluctuate with age. A
      dimensional component to neural foundations for multiple developmental disorders
      makes the study of normal individual brain differences in development even more
      important to understand both normal and clinical cognitive behavioral outcomes
      throughout life.

PMID- 24565943
TI  - [Halothane at a liquid state in the ventilatory circuit: a rare incident of
      anesthesia].

PMID- 24565942
TI  - The developmental transcriptome of the human brain: implications for
      neurodevelopmental disorders.
AB  - PURPOSE OF REVIEW: Recent characterizations of the transcriptome of the
      developing human brain by several groups have generated comprehensive datasets on
      coding and noncoding RNAs that will be instrumental for illuminating the
      underlying biology of complex neurodevelopmental disorders. This review
      summarizes recent studies successfully utilizing these data to increase our
      understanding of the molecular mechanisms of pathogenesis. RECENT FINDINGS:
      Several approaches have successfully integrated developmental transcriptome data
      with gene discovery to generate testable hypotheses about when and where in the
      developing human brain disease-associated genes converge. Specifically, these
      include the projection neurons in the prefrontal and primary motor--somatosensory
      cortex during mid-fetal development in autism spectrum disorder and the frontal
      cortex during fetal development in schizophrenia. SUMMARY: Developmental
      transcriptome data is a key to interpreting disease-associated mutations and
      transcriptional changes. Novel approaches integrating the spatial and temporal
      dimensions of these data have increased our understanding of when and where
      disease occurs. Refinement of spatial and temporal properties and expanding these
      findings to other neurodevelopmental disorders will provide critical insights for
      understanding disease biology.

PMID- 24565944
TI  - [Guidelines for nutrition support in critically ill patient].

PMID- 24565945
TI  - [Which is the legal risk associated with day surgery for the anaesthesiologist?].

PMID- 24565946
TI  - [Perioperative hemodynamic optimization by a closed loop system: the
      anesthesiologist must remain in control!].

PMID- 24565947
TI  - Glycine propionyl l-carnitine attenuates d-Galactosamine induced fulminant
      hepatic failure in wistar rats.
AB  - Glycine propionyl l-carnitine (GPLC) is a propionyl ester of carnitine that
      includes an additional glycine component. The present study evaluated
      hepatoprotective effect of GPLC in d-Galactosamine (d-GalN) induced fulminant
      hepatic failure. Rats were intraperitonially administered d-GalN (700mg/kgBW).
      GPLC was given as a pre-treatment (35mg/kgBW/day) for 1month followed by a single
      dose of d-GalN on the 31st day. d-GalN administration resulted in increased
      mortality and serum ALT and AST activities. These increases were significantly
      attenuated by GPLC. d-GalN treatment increased hepatic lipid peroxidation and a
      decrease in reduced glutathione content was observed. GPLC pre-treatment
      significantly decreased lipid peroxidation and augmented the level of GSH. d-GalN
      increased the circulating level of TNF-alpha and ATM-Kinase and MAP-Kinase
      expression. GPLC supplementation inhibited the increase in serum TNF-alpha and
      ATM-Kinase and MAP-Kinase expression. d-GalN treatment increased the level of Bax
      and Caspase-3 m-RNA while as a decline was observed in Bcl2 m-RNA. GPLC prevented
      the increase in Caspase-3 and Bax m-RNA and at the same time augmented the
      expression of Bcl2 m-RNA. Our findings suggest that GPLC alleviates d-GalN
      induced liver injury by strengthening antioxidative defense system and reducing
      apoptotic signalling pathways. 

PMID- 24565948
TI  - Evolution and biogeography of gymnosperms.
AB  - Living gymnosperms comprise only a little more than 1000 species, but represent
      four of the five main lineages of seed plants, including cycads, ginkgos,
      gnetophytes and conifers. This group has huge ecological and economic value, and
      has drawn great interest from the scientific community. Here we review recent
      advances in our understanding of gymnosperm evolution and biogeography, including
      phylogenetic relationships at different taxonomic levels, patterns of species
      diversification, roles of vicariance and dispersal in development of
      intercontinental disjunctions, modes of molecular evolution in different genomes
      and lineages, and mechanisms underlying the formation of large nuclear genomes.
      It is particularly interesting that increasing evidence supports a sister
      relationship between Gnetales and Pinaceae (the Gnepine hypothesis) and the
      contribution of recent radiations to present species diversity, and that
      expansion of retrotransposons is responsible for the large and complex nuclear
      genome of gymnosperms. In addition, multiple coniferous genera such as Picea very
      likely originated in North America and migrated into the Old World, further
      indicating that the center of diversity is not necessarily the place of origin.
      The Bering Land Bridge acted as an important pathway for dispersal of gymnosperms
      in the Northern Hemisphere. Moreover, the genome sequences of conifers provide an
      unprecedented opportunity and an important platform for the evolutionary studies
      of gymnosperms, and will also shed new light on evolution of many important gene
      families and biological pathways in seed plants. 

PMID- 24565949
TI  - Assessing competencies: an evaluation of ASTD's Certified Professional in
      Learning and Performance (CPLP) designation.
AB  - The American Society of Training and Development's (ASTD) Certified Professional
      in Learning and Performance (CPLP) program is purported to be based on the ASTD's
      competency model, a model which outlines foundational competencies, roles, and
      areas of expertise in the field of training and performance improvement. This
      study seeks to uncover the relationship between the competency model and the CPLP
      knowledge exam questions and work product submissions (two of the major
      instruments used to test for competency of CPLP applicants). A mixed qualitative
      quantitative approach is used to identify themes, quantify relationships, and
      assess questions and guidelines. Multiple raters independently analyzed the data
      and identified key themes, and Fleiss' Kappa coefficient was used in measuring
      inter-rater agreement. The study concludes that several discrepancies exist
      between the competency model and the knowledge exam and work product submission
      guidelines. Recommendations are given for possible improvement of the CPLP
      program. 

PMID- 24565950
TI  - Polychemotherapy or gemcitabine in advanced pancreatic cancer: a meta-analysis.
AB  - BACKGROUND: Gemcitabine monotherapy is the cornerstone of treatment for advanced
      pancreatic cancer. To date, no clear survival benefit has been found when
      combination chemotherapy has been compared with gemcitabine alone, except in a
      few studies. This meta-analysis compared the efficacy of polychemotherapy with
      gemcitabine alone in advanced pancreatic cancer. METHODS: Randomised trials
      comparing combination chemotherapy with gemcitabine alone were identified through
      electronic searches of PubMed, EMBASE, Web of Science, and the Cochrane Central
      Register of Controlled Trials. Overall survival, reported as the hazard ratio at
      the 95% confidence interval, was the primary outcome measure. RESULTS: 29 trials
      (19 phase III and 10 small randomised trials) that included 8421 patients were
      identified. Overall, polychemotherapy significantly improved overall survival
      (hazard ratio=0.87; 95% CI, 0.81-0.93; P<0.0001), progression-free survival
      (hazard ratio=0.77; 95% CI, 0.70-0.84; P<0.00001), and response rate (risk
      ratio=1.71; 95% CI, 1.42-2.07; P<0.00001) compared with gemcitabine alone.
      CONCLUSIONS: Compared with gemcitabine monotherapy, combinations of two or more
      drugs (particularly those with novel agents or associated with >20% response
      rates and triplets) improved outcomes and response rate in advanced pancreatic
      cancer, and they could be considered a new standard of care in advanced settings.

PMID- 24565951
TI  - Progress in assessing animal welfare in relation to new legislation:
      opportunities for behavioural researchers.
AB  - Recent revisions to international legislation and guidelines on the care and use
      of animals in research and testing emphasise the importance of minimising
      suffering and improving welfare. Achieving this requires effective systems for
      recognising, recording, analysing and assessing animal behaviour, in order to
      identify relevant indicators of pain, suffering, distress or lasting harm so that
      any suffering can be rapidly recognised and ameliorated. Behavioural researchers
      can assist by disseminating information on developments in techniques and
      approaches for recognising, observing, monitoring, analysing and interpreting
      behaviour, both within their own facilities and more widely. They can also help
      to facilitate better welfare assessment by continuing to develop systems for
      measuring behaviours - including indicators of positive welfare - while also
      ensuring that harms within behavioural research are minimised. 

PMID- 24565952
TI  - Genetic architecture of naturally occurring quantitative traits in plants: an
      updated synthesis.
AB  - Deciphering the genetic and molecular bases of quantitative variation is a long
      standing challenge in plant biology because it is essential for understanding
      evolution and for accelerating plant breeding. Recent multi-trait analyses at
      different phenotypic levels are uncovering the pleiotropy and the genetic
      regulation underlying high-level complex traits. Thus, the number of known causal
      loci, genes and nucleotide polymorphisms is expanding. Current plant causal
      catalogs contain ~400 genes and natural polymorphisms revealing several
      dysfunctional allelic series that involve multiple mutations. In addition,
      repeated evolution of quantitative traits mediated by large effect alleles is
      found across plant phylogeny. Finally, systematic analyses of genetic and
      environmental interactions are beginning to elucidate the molecular mechanisms of
      relevant interactions. 

PMID- 24565954
TI  - Comment on Corbett et al. entitled "Acupuncture and other physical treatments for
      the relief of pain due to osteoarthritis of the knee: network meta-analysis".

PMID- 24565953
TI  - Osteoarthritis and the rule of halves.
AB  - BACKGROUND: Symptomatic osteoarthritis poses a major challenge to primary health
      care but no studies have related accessing primary care ('detection'), receiving
      recommended treatments ('treatment'), and achieving adequate control ('control').
      OBJECTIVE: To provide estimates of detection, treatment, and control within a
      single population adapting the approach used to determine a Rule of Halves for
      other long-term conditions. SETTING: General population. PARTICIPANTS: 400 adults
      aged 50+ years with prevalent symptomatic knee osteoarthritis. DESIGN:
      Prospective cohort with baseline questionnaire, clinical assessment, and plain
      radiographs, and questionnaire follow-up at 18 and 36 months and linkage to
      primary care medical records. OUTCOME MEASURES: 'Detection' was defined as at
      least one musculoskeletal knee-related GP consultation between baseline and 36
      months. 'Treatment' was self-reported use of at least one recommended treatment
      or physiotherapy/hospital specialist referral for their knee problem at all three
      measurement points. Pain was 'controlled' if characteristic pain intensity <5 out
      of 10 on at least two occasions. RESULTS: In 221 cases (55.3%; 95%CI: 50.4, 60.1)
      there was evidence that the current problem had been detected in general
      practice. Of those detected, 164 (74.2% (68.4, 80.0)) were receiving one or more
      of the recommended treatments at all three measurement points. Of those detected
      and treated, 45 (27.4% (20.5, 34.3)) had symptoms under control on at least two
      occasions. Using narrower definitions resulted in substantially lower estimates.
      CONCLUSION: Osteoarthritis care does not conform to a Rule of Halves. Symptom
      control is low among those accessing health care and receiving treatment.

PMID- 24565957
TI  - Ethics of facial transplantation revisited.
AB  - PURPOSE OF REVIEW: There have been 26 cases of facial transplantation reported,
      and three deaths, 11.5%. Mortality raises the issue of risk versus benefit for
      face transplantation, a procedure intended to improve quality of life, rather
      than saving life. Thus, one of the most innovative surgical procedures has opened
      the debate on the ethical, legal, and philosophical aspects of face
      transplantation. RECENT FINDINGS: Morbidity in face transplant recipients
      includes infections and metabolic consequences. No graft loss caused by technical
      failure, hyperacute, or chronic graft rejection or graft-versus-host disease has
      been reported. One case of posttransplant lymphoproliferative disorder, 3.45% and
      one case of lymphoma in an HIV-positive recipient were reported. Psychological
      issues in candidates can include chronic pain, mood disorders, preexisting
      psychotic disorders, post-traumatic stress disorder (PTSD), and substance abuse.
      SUMMARY: Early publications on ethical aspects of face transplantation focused
      mainly on informed consent. Many other ethical issues have been identified,
      including lack of coercion, donor family consent and confidentiality, respect for
      the integrity of the donor's body, and financial promotion of the recipient and
      transplant team, as well as the cost to society for such a highly technical
      procedure, requiring lifelong immunosuppression.

PMID- 24565955
TI  - Serum biomarkers of bone metabolism in castration-resistant prostate cancer
      patients with skeletal metastases: results from SWOG 0421.
AB  - BACKGROUND: Prior studies suggest that elevated markers of bone turnover are
      prognostic for poor survival in castration-resistant prostate cancer (CRPC). The
      predictive role of these markers relative to bone-targeted therapy is unknown. We
      prospectively evaluated the prognostic and predictive value of bone biomarkers in
      sera from CRPC patients treated on a placebo-controlled phase III trial of
      docetaxel with or without the bone targeted endothelin-A receptor antagonist
      atrasentan (SWOG S0421). METHODS: Markers for bone resorption (N-telopeptide and
      pyridinoline) and formation (C-terminal collagen propeptide and bone alkaline
      phosphatase) were assayed in pretreatment and serial sera. Cox proportional
      hazards regression models were fit for overall survival. Models were fit with
      main effects for marker levels and with/without terms for marker-treatment
      interaction, adjusted for clinical variables, to assess the prognostic and
      predictive value of atrasentan. Analysis was adjusted for multiple comparisons.
      Two-sided P values were calculated using the Wald test. RESULTS: Sera from 778
      patients were analyzed. Elevated baseline levels of each of the markers were
      associated with worse survival (P < .001). Increasing marker levels by week nine
      of therapy were also associated with subsequent poor survival (P < .001).
      Patients with the highest marker levels (upper 25th percentile for all markers)
      not only had a poor prognosis (hazard ratio [HR] = 4.3; 95% confidence interval
      [CI] = 2.41 to 7.65; P < .001) but also had a survival benefit from atrasentan
      (HR = 0.33; 95% CI = 0.15 to 0.71; median survival = 13 [atrasentan] vs 5 months
      [placebo]; P interaction = .005). CONCLUSIONS: Serum bone metabolism markers have
      statistically significant independent prognostic value in CRPC. Importantly, a
      small group of patients (6%) with highly elevated markers of bone turnover appear
      to preferentially benefit from atrasentan therapy.

PMID- 24565956
TI  - A prospective study of macrophage inhibitory cytokine-1 (MIC-1/GDF15) and risk of
      colorectal cancer.
AB  - BACKGROUND: Chronic inflammation plays a role in the development of colorectal
      cancer (CRC). The novel plasma inflammatory biomarker macrophage inhibitory
      cytokine-1 (MIC-1, GDF15) may have a direct mechanistic role in colorectal
      carcinogenesis. METHODS: We conducted a prospective, nested, case-control study
      of incident CRC among men and women who provided a prediagnostic blood specimen.
      We used an enzyme-linked immunosorbent assay to measure MIC-1 and examined
      associations between quintiles of MIC-1 and CRC using logistic regression
      adjusted for matching factors (age and date of blood draw), risk factors, and
      other plasma inflammatory markers. We also assessed the relationship between MIC
      1 levels and prostaglandin-endoperoxide synthase 2 (PTGS2)/cyclooxygenase-2 (COX
      2) enzyme status in tumors with available tissue for analysis. All statistical
      tests were two-sided. RESULTS: Compared with men and women within the lowest
      quintile of plasma MIC-1, the multivariable relative risk (RR) for CRC was 1.93
      (95% confidence interval [CI] = 1.27 to 2.94) for the highest quintile (P linear
      trend = .004). In an exploratory analysis, we found that among individuals with
      high plasma MIC-1 levels (quintiles 2-5), compared with nonuse, regular use of
      aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) was associated with a
      lower risk of PTGS2-positive CRC (multivariable RR = 0.60; 95% confidence
      interval = 0.41 to 0.88) but not PTGS2-negative CRC (multivariable RR = 1.21; 95%
      CI = 0.71 to 2.07). In contrast, among individuals with low MIC-1 levels
      (quintile 1), aspirin and NSAID use was not associated with a lower risk of PTGS2
      positive CRC (multivariable RR = 0.57; 95% CI = 0.21 to 1.54) or PTGS2-negative
      CRC (multivariable RR = 1.41; 95% CI = 0.47 to 4.23). CONCLUSIONS: Our results
      support an association between higher levels of circulating MIC-1 (GDF15) and
      CRC. Aspirin/NSAID use appeared to lower risk of PTGS2-positive cancers,
      particularly among individuals with high levels of circulating MIC-1.

PMID- 24565958
TI  - Impact of brain death on ischemia/reperfusion injury in liver transplantation.
AB  - PURPOSE OF REVIEW: In liver transplantation, the ischemia/reperfusion injury
      (IRI) is influenced by factors related to graft quality, organ procurement and
      the transplant procedure itself. However, in brain-dead donors, the process of
      death itself also thoroughly affects organ damage through breakdown of the
      autonomous nervous system and subsequent massive cytokine release. This review
      highlights the actual knowledge on these proinflammatory effects of brain death
      on IRI in liver transplantation. RECENT FINDINGS: Brain death affects IRI either
      through hemodynamical or molecular effects with proinflammatory activation.
      Immunological effects are mainly mediated through Kupffer cell activation,
      leading to TNF-alpha and TLR4 amplification. Proinflammatory cytokines such as
      interleukin (IL)-6, IL-10, TNF-beta and MIP-1alpha are released, together with
      activation of the innate immune system via natural killer cells and natural
      killer T cells, which promote organ damage and activation of fibrosis.
      Preprocurement treatment regimens attempt to hamper inflammatory response by the
      application of methylprednisolone or thymoglobulin to the donor. Selective P
      selectin antagonism resulted in improved function in marginal liver grafts.
      Inhaled nitric oxide was found to reduce apoptosis in liver grafts. Other
      medications like the immunosuppressant tacrolimus produced conflicting results
      regarding organ protection. Furthermore, improved organ storage after procurement
      - such as machine perfusion - can diminish effects of IRI in a clinical setting.
      SUMMARY: Brain death plays a fundamental role in the regulation of molecular
      markers triggering inflammation and IRI-related tissue damage in liver
      transplants. Although several treatment options have reached clinical
      application, to date, the effects of brain death during donor conditioning and
      organ procurement remain relevant for organ function and survival.

PMID- 24565959
TI  - Procurement for visceral organ transplantation: where to cannulate and how to
      perfuse?
AB  - PURPOSE OF REVIEW: Despite significant improvements in visceral organ
      transplantation over the last few decades, some technical aspects of organ
      harvesting remain controversial. The purpose of this article is to review and
      summarize the latest literature on how to perfuse in multiorgan procurement.
      RECENT FINDINGS: Few prospective studies have analyzed and compared technical
      aspects of harvesting such as cannulation (aortic-only versus dual aortic and
      portal flush), flush rates and volumes as well as flush pressures (high pressure
      vs. gravity). However, these and most data available from additional
      retrospective and experimental studies do not clearly support one harvesting
      technique over another. SUMMARY: Currently, because of lack of superiority data,
      no clear guidelines exist on what cannulation techniques to apply during organ
      procurements in visceral organ transplantation. Additional prospective trials are
      needed to clarify these questions.

PMID- 24565960
TI  - Lens culinaris agglutinin-reactive alpha-fetoprotein decline after transcatheter
      arterial chemoembolization in patients with hepatocellular carcinoma predicts
      survival.
AB  - BACKGROUND: Lens culinaris agglutinin-reactive alpha-fetoprotein (AFP-L3) is a
      fucosylated fraction of AFP that is highly specific for hepatocellular carcinoma
      (HCC). We studied the relationship between AFP-L3 response and treatment outcome
      in terms of radiologic response and overall survival in patients undergoing
      transcatheter arterial chemoembolization (TACE). METHODS: We retrospectively
      analyzed 152 patients with advanced HCC undergoing TACE. Serum AFP-L3 and AFP
      levels were measured simultaneously with a novel lectin dual-label time-resolved
      immunofluorometric assay (lectin dual-label TRFIA). AFP-L3 response was defined
      as a >=20% reduction in AFP-L3 level after a minimum of 2 cycles of chemotherapy.
      RESULTS: A total of 47 AFP-L3 responders had improved median overall survival of
      42.9 months compared with 15.4 months in nonresponders (P<0.0001), and AFP-L3
      response was strongly associated with radiologic response (P<0.0001). The
      combination of AFP-L3 response and serum AFP response provided further prognostic
      information. On multivariate analysis, the prognostic value of AFP-L3 response
      was independent of maximum tumor diameter and BCLC stage. CONCLUSION: A
      significant reduction in AFP-L3 in patients with advanced HCC is an important
      predictor of survival. Achieving an AFP-L3 response should be one of the
      therapeutic intents of TACE.

PMID- 24565961
TI  - Airway obstruction after the development of Hashimoto's thyroiditis.

PMID- 24565962
TI  - New cytotoxic compounds from flowers of Lawsonia inermis L.
AB  - Three new compounds, a bicoumarin A (1), a biflavonoid A (2), and a biquinone A
      (3), as well as 12 other known compounds, were isolated from the flower of
      Lawsonia inermis L. The structures were elucidated by spectral analysis and new
      compounds 2 and 3 then were further confirmed by ECD calculations and single
      crystal X-ray diffraction crystallography respectively. The cytotoxicity of the
      compounds against four cancer cell lines, including MCF-7, Hela, HCT-116, and HT
      29 were evaluated using MTT assay. The IC50 values of compounds 3 and 5 against
      MCF-7, Hela, HCT-116, and HT-29 were 2.24, 1.42, 24.29, and 7.02 MUM and 6.1,
      2.44, 5.58, and 10.21 MUM respectively. The two compounds exhibited stronger
      inhibitory activities than the positive control 5-fluorouracil (IC50=7.34, 11.50,
      36.17, 18.83 MUM) against the four tested cell lines. These results demonstrated
      that compounds from the flowers of L. inermis L. showed cytotoxic activity on MCF
      7, Hela, HCT-116, and HT-29 cell lines.

PMID- 24565963
TI  - Sesquiterpene lactones from Mikania micrantha and Mikania cordifolia and their
      cytotoxic and anti-inflammatory evaluation.
AB  - The guaianolide 8-epi-mikanokryptin (1) and the melampolide 11Hbeta-11,13
      dihydromicrantholide (2) along with known sesquiterpene lactones (3-13) and other
      constituents were isolated from the aerial parts of different populations of
      Mikania micrantha and Mikania cordifolia collected in several states of Mexico.
      The relative and absolute configurations of 1 were determined by X-ray
      diffraction and CD analysis, respectively. Considering the (1)H and (13)C NMR
      chemical shift similarities and the H-H coupling constant values, a [(1)D(14),
      (15)D5] conformation was established for micrantholides (2, 8-13). We tested
      nearly all the sesquiterpene lactones for antiproliferative activity in human
      cancer cell lines, and they exhibited moderate activity. Additionally, in a mouse
      ear model of edema induced by TPA, the anti-inflammatory activities were
      marginal. 

PMID- 24565964
TI  - Unreliability of the use of thyroglobulin concentration in postmortem blood
      samples in forensic diagnosis.
AB  - Previous studies have reported that the concentration of thyroglobulin (Tg) in
      heart blood is high in cases of asphyxia by neck compression such as hanging,
      strangulation, and throttling and in those with traumatic injuries to the head.
      However, we have experienced cases in which we observed high Tg concentrations
      without such findings. Therefore, we analyzed the influence of postmortem changes
      on Tg concentration. Of 253 forensic autopsies conducted at our institution, we
      analyzed 44 cases without the findings presumed to increase Tg concentration. We
      collected right heart blood (RHB) and left heart blood (LHB) separately and
      measured Tg concentrations in each. The Tg concentration of the RHB in 19 (43%)
      cases and that of the LHB in 10 (23%) cases was higher than the standard value
      (200ng/ml) obtained in previous studies. In some cases, we found large
      differences between the Tg concentrations of RHB and LHB. We suggest that Tg
      concentration can increase above the standard value and that a difference between
      the Tg concentration of RHB and LHB arises as a result of postmortem changes.
      Consequently, if there is a large difference between the Tg concentration of RHB
      and LHB, the concentration of Tg should not be used as a basis for forensic
      diagnosis. 

PMID- 24565965
TI  - Genetic analysis of 17 Y-chromosomal STR loci of Chinese Tujia ethnic group
      residing in Youyang Region of Southern China.
AB  - Y-STR haplotype data were obtained in a population sample of 197 unrelated
      healthy male individuals of Chinese Tujia ethnic minority group residing in an
      autonomous county of Southern China using 17 Y-chromosome STR markers. A total of
      197 haplotypes were identified in the set of Y-STR loci. The overall haplotype
      diversity for the Tujia population at 17 Y-STR loci was 1.0000+/-0.0005. Genetic
      distance was estimated between this population and other 14 Chinese populations
      including Paiwan and Atayal populations of Taiwan, and Southern Han, Dong, Jing,
      Miao, Yao, Zhuang, Yi, Maonan, She, Hui, Sala, and Tibetan ethnic groups. The
      results demonstrated that the 17 Y-STR loci analyzed were highly polymorphic in
      Tujia ethnic group examined and hence useful for forensic cases, paternity
      testing, and population genetic studies. 

PMID- 24565966
TI  - Re: Delila Gasi Tandefelt, Joost L. Boormans, Hetty A. van der Korput, Guido W.
      Jenster, Jan Trapman. A 36-gene signature predicts clinical progression in a
      subgroup of ERG-positive prostate cancers. Eur Urol 2013;64:941-50.

PMID- 24565967
TI  - Re: Anna Bill-Axelson, Hans Garmo, Lars Holmberg, et al. Long-term distress after
      radical prostatectomy versus watchful waiting in prostate cancer: a longitudinal
      study from the Scandinavian Prostate Cancer Group-4 randomized clinical trial.
      Eur Urol 2013;64:920-8.

PMID- 24565968
TI  - Polyphenols bearing cinnamaldehyde scaffold showing cell growth inhibitory
      effects on the cisplatin-resistant A2780/Cis ovarian cancer cells.
AB  - Ovarian carcinoma remains the most lethal among gynecological cancers.
      Chemoresistance is a clinical problem that severely limits treatment success. To
      identify potent anticancer agents against the cisplatin-resistant human ovarian
      cancer cell line A2780/Cis, 26 polyphenols bearing a cinnamaldehyde scaffold were
      synthesized. Structural differences in their inhibitory effect on clonogenicity
      of A2780/Cis cells were elucidated using comparative molecular field analysis and
      comparative molecular similarity indices analysis. Structural conditions required
      for increased inhibitory activity can be derived based on the analysis of their
      contour maps. The two most active compounds (16 and 19) were selected and further
      characterized their biological activities. We found that compounds 16 and 19
      trigger cell cycle arrest at the G2/M phase and apoptotic cell death in cisplatin
      resistant A2780/Cis human ovarian cancer cells. The molecular mechanism of
      compound 16 was elucidated using in vitro aurora A kinase assay, and the binding
      mode between the compound 16 and aurora A kinase was interpreted using in silico
      docking experiments. The findings obtained here may help us develop novel plant
      derived polyphenols used for potent chemotherapeutic agents. In conclusion,
      compounds 16 and 19 could be used as promising lead compounds for the development
      of novel anticancer therapies in the treatment of cisplatin-resistant ovarian
      cancers. 

PMID- 24565969
TI  - Design, synthesis and biological evaluation of novel 6-alkenylamides substituted
      of 4-anilinothieno[2,3-d]pyrimidines as irreversible epidermal growth factor
      receptor inhibitors.
AB  - A novel series of 6-alkenylamides of 4-anilinothieno[2,3-d]pyrimidine derivatives
      was designed, synthesized and evaluated as irreversible inhibitors of the
      epidermal growth factor receptor (EGFR). Most of the compounds exhibited good
      potency against EGFR wild type (EGFR wt) and EGFR T790M/L858R. Among these, the
      half-maximal inhibitory concentration (IC50) values of 17 compounds against EGFR
      wt were less than 0.020MUM, and those of 12 compounds were less than 0.010MUM.
      The IC50 values of 10 compounds against EGFR T790M/L858R were less than 0.005MUM.
      Compounds 8l, 9n, 9o, 9q and 9v almost completely blocked the phosphorylation of
      EGFR in the A431 cell line at 1MUM. Compounds 8l, 9n, 9o, 9q and 9v blocked the
      autophosphorylation of EGFR in NCI-H1975 cells at high concentration (1MUM), and
      compound 8l was confirmed to be an irreversible inhibitor through the dilution
      method. 

PMID- 24565970
TI  - Stereoselective preparation of pyridoxal 1,2,3,4-tetrahydro-beta-carboline
      derivatives and the influence of their absolute and relative configuration on the
      proliferation of the malaria parasite Plasmodium falciparum.
AB  - We have selectively synthesized by Pictet-Spengler condensation of tryptophan and
      pyridoxal the four stereoisomers of a pyridoxal beta-carboline derivative that
      was designed to inhibit the proliferation of Plasmodium falciparum. Biological
      investigation of the four compounds revealed that they all inhibit the growth of
      P. falciparum. With an IC50 value of 8 +/- 1 MUM, the highest inhibitory effect
      on the proliferation of the parasite was found for the 1,3-trans-substituted
      tetrahydro-beta-carboline that was obtained from d-tryptophan. Lower activity was
      found for its enantiomer, while the two diastereomeric cis-products were markedly
      less effective. Apparently a distinct spacial orientation of the carboxyl group
      of the substituted tetrahydropyridine unit of the compounds is needed for high
      activity, while the absolute configuration of the molecules is of lesser
      importance.

PMID- 24565971
TI  - Study of anti-fibrillogenic activity of iron(II) clathrochelates.
AB  - The macrocyclic compounds mono- and bis-iron(II) clathrochelates were firstly
      studied as potential anti-fibrillogenic agents using fluorescent inhibitory
      assay, atomic force microscopy and flow cytometry. It is shown that presence of
      the clathrochelates leads to the change in kinetics of insulin fibrillization
      reaction and reduces the amount of formed fibrils (up to 70%). The nature of
      ribbed substituent could determine the activity of clathrochelates-the higher
      inhibitory effect is observed for compounds containing carboxybenzenesulfide
      groups, while the inhibitory properties only slightly depend on the size of
      complex species. The mono- and bis-clathrochelate derivatives of meta
      mercaptobenzoic acid have close values of IC50 namely 16 +/- 2 and 24 +/- 5 MUM,
      respectively. The presence of clathrochelates decreases the fibril diameter from
      5-12 nm for free insulin fibrils to 3-8 nm for these formed in the clathrochelate
      presence, it also prevents the lateral aggregation of mature fibrils and
      formation of superfibrillar clusters. However the addition of clathrochelate
      results in more heterogeneous (both by size and structure) insulin aggregates
      population as compared to the free insulin. This way, cage complexes-iron(II)
      clathrochelates are proposed as efficient agents able to suppress the protein
      aggregation processes.

PMID- 24565972
TI  - Development of novel tetrahydrothieno[2,3-c]pyridine-3-carboxamide based
      Mycobacterium tuberculosis pantothenate synthetase inhibitors: molecular
      hybridization from known antimycobacterial leads.
AB  - Twenty six 2,6-disubstituted 4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3
      carboxamide derivatives were designed by molecular hybridization approach using
      and synthesized from piperidin-4-one by five step synthesis. Compounds were
      evaluated for Mycobacterium tuberculosis (MTB) pantothenate synthetase (PS)
      inhibition study, in vitro activities against MTB, cytotoxicity against RAW 264.7
      cell line. Among the compounds, 6-(4-nitrophenylsulfonyl)-2-(5-nitrothiophene-2
      carboxamido)-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carboxamide (11) was found
      to be the most active compound with IC50 of 5.87 +/- 0.12 MUM against MTB PS,
      inhibited MTB with MIC of 9.28 MUM and it was non-cytotoxic at 50 MUM. The
      binding affinity of the most potent inhibitor 11 was further confirmed
      biophysically through differential scanning fluorimetry.

PMID- 24565974
TI  - On the importance of statistics in breath analysis--hope or curse?

PMID- 24565976
TI  - Ray Wu as Fifth Business: Deconstructing collective memory in the history of DNA
      sequencing.
AB  - The concept of 'Fifth Business' is used to analyze a minority standpoint and
      bring serious attention to the role of scientists who play a galvanizing role in
      a science but for multiple reasons appear less prominently in more common
      recounts of any particular development. Biochemist Ray Wu (1928-2008) published a
      DNA sequencing experiment in March 1970 using DNA polymerase catalysis and
      specific nucleotide labeling, both of which are foundational to general
      sequencing methods today. The scant mention of Wu's work from textbooks, research
      articles, and other accounts of DNA sequencing calls into question how scientific
      collective memory forms. This alternative history seeks to understand why a key
      figure in nucleic acid sequence analysis has remained less visibly connected or
      peripheral to solidifying narratives about the history of DNA sequencing. The
      study resists predictable dismissals of Wu's work in order to seriously examine
      the formation of his nucleic acid sequence analysis research program and how he
      shared his knowledge of sequencing during a period of rapid advancement in the
      field. An analysis of Wu's work on sequencing the cohesive ends of lambda
      bacteriophage in the 1960s and 1970s exemplifies how a variety of individuals and
      groups attempted to develop protocol for sequencing the order of nucleotide base
      pairs comprising DNA. This historical examination of the sociality of scientific
      research suggests a way to understand how Wu and others contributed to the very
      collective memory of DNA sequencing that Wu eventually tried to repair. The study
      of Wu, who was a Chinese immigrant to the United States, provides a foundation
      for further critical scholarship on the heterogeneous histories of Asian American
      bioscientists, the sociality of their scientific works, and how the resulting
      knowledge produced is preserved, if not evenly, in a scientific field's
      collective memory.

PMID- 24565973
TI  - T cell interleukin-15 surface expression in chimpanzees infected with human
      immunodeficiency virus.
AB  - Interleukin-15 (IL-15) contributes to natural killer cell development and immune
      regulation. However, IL-15 and interferon-gamma (IFN-gamma) production are
      significantly reduced during progression to AIDS. We have previously reported
      that HIV infected chimpanzees (Pan troglodytes) express CD3-CD8+ IFN-gamma+
      natural killer (NK) cells with an inverse correlation to plasma HIV viral load.
      To expand on our initial study, we examined a larger population of HIV infected
      chimpanzees (n=10). Whole blood flow cytometry analyses showed that recombinant
      gp120 (rgp120) or recombinant IL-15 induces specific CD3-CD8+ IFN-gamma+ NK cells
      at higher levels than CD3+CD8+ IFN-gamma+ T cells in HIV infected specimens.
      Interestingly, peripheral blood T cells exhibited 0.5-3% IL-15 surface Tcell/NKT
      cell phenotypes, and rIL-15 stimulation significantly (P<0.007) up-regulated
      CD4+CD25+ T cell expression. Importantly, these data demonstrate novel T cell
      interleukin-15 expression and indicate a plausible regulatory mechanism for this
      cell-type during viral infection. 

PMID- 24565978
TI  - [Primary varicella infection in an immunocompetent patient resulting in severe
      pneumonia and meningoencephalitis].

PMID- 24565977
TI  - Coadministration of antigen-conjugated and free CpG: effects of in vitro and in
      vivo interactions in a murine model.
AB  - CpG oligodeoxynucleotides (CpG) are widely studied as promising adjuvants in
      vaccines against a range of diseases including infection, cancer or allergy.
      Conjugating antigen to CpG has been shown to potentiate the adjuvant effect via
      enhancing antigen uptake and danger signaling by the very same cell. In the
      present study, using biotinylated CpG and streptavidin as a model system, we
      demonstrate that CpG motif containing free and antigen-conjugated
      oligonucleotides do not compete in terms of cell activation via TLR9, but do
      compete for cellular uptake. Antigen-conjugated CpG enhances cellular association
      and uptake of the antigen by antigen-presenting cells (APC) and T cells. Free CpG
      efficiently competes with antigen-CpG conjugates in BMDC and T cells, but shows
      weak or no competition in B cells that have higher TLR9 expression. Vaccination
      with antigen-conjugated CpG or with a mixture of antigen and CpG elevates the
      level of antigen-specific antibodies but co-administration of CpG-antigen
      conjugates and free CpG adversely effects immunogenicity. These observations may
      help optimize CpG-based vaccine formulation. 

PMID- 24565979
TI  - Quantifying transitions in response allocation with change point analysis in
      concurrent chains.
AB  - Research based on the matching law has demonstrated empirically that the physical
      and temporal properties of the events, the context in which they occur and the
      signals that mark them in space and time all contribute to response allocation.
      When the physical or temporal properties of different outcomes change in ways
      that affect their relative value, the ratio of responses to each outcome adjusts
      with time and exposure to the new contingency. Five pigeons pecked in concurrent
      chain schedules with fixed-interval terminal links. Terminal-link schedules were
      changed each session. In most sessions, response allocation was initially
      indifferent to terminal-link schedules but shifted to favor the initial link
      associated with the shorter terminal link. As a first step to disambiguating
      response allocation in transition from stable response allocation, transition
      durations were interpolated from change points in cumulative response plots. The
      relation between transition duration and absolute log immediacy ratio was
      negative: the number of initial links until the shift occurred was longer when
      terminal-link schedules were relatively similar than when they were relatively
      different. 

PMID- 24565980
TI  - A comparative analysis of auditory perception in humans and songbirds: a modular
      approach.
AB  - We propose that a relatively small number of perceptual skills underlie human
      perception of music and speech. Humans and songbirds share a number of features
      in the development of their auditory communication systems. These similarities
      invite comparisons between species in their auditory perceptual skills. Here, we
      summarized our experimental comparisons between humans (and other mammals) and
      songbirds (and other birds) in their use of pitch height and pitch chroma
      perception and discuss similarities and differences in other auditory perceptual
      abilities of these species. Specifically, we introduced a functional modular
      view, using pitch chroma and pitch height perception as examples, as a
      theoretical framework for the comparative study of auditory perception and
      perhaps all of the study of comparative cognition. We also contrasted phylogeny
      and adaptation as causal mechanisms in comparative cognition using examples from
      auditory perception. 

PMID- 24565981
TI  - Influence of trait anxiety on the effects of acute stress on learning and
      retention of the passive avoidance task in male and female mice.
AB  - The influence of anxiety on the effects of acute stress for the acquisition and
      retention of passive avoidance conditioned task was evaluated in male and female
      mice. Animals were categorized as high-, medium-, and low-anxiety according to
      their performance in the elevated plus-maze test. Subsequently, half of the mice
      in each group were exposed to an acute stressor and assayed in an aversive
      conditioning test two days later. Exposure to restraint stress before inhibitory
      avoidance conditioning had a differential impact on the conditioned response of
      males and females according to their trait anxiety. The acute stressor
      significantly altered the conditioned response of mice with a high-anxiety level.
      The long-term effect of the stressor varied for each sex; high-anxiety stressed
      males showed an enhanced conditioned response with respect to their controls,
      whereas high-anxiety stressed females presented an impaired performance. These
      results lead us to believe that the characterization of individuality is an
      important factor in understanding the interaction between stress and memory for
      each sex; the trait anxiety of our animals modulated the effects of stress on the
      conditioned response so that males and females performed in contrasting manners
      to the same environmental stimuli and experimental conditions. 

PMID- 24565982
TI  - A good time to leave?: the sunk time effect in pigeons.
AB  - Persistence in a losing course of action due to prior investments of time, known
      as the sunk time effect, has seldom been studied in nonhuman animals. On every
      trial in the present study, pigeons were required to choose between two response
      keys. Responses on one key produced food after a short fixed interval (FI) of
      time on some trials, or on other trials, no food (Extinction) after a longer
      time. FI and Extinction trials were not differently signaled, were equiprobable,
      and alternated randomly. Responses on a second Escape key allowed the pigeon to
      terminate the current trial and start a new one. The optimal behavior was for
      pigeons to peck the escape key once the duration equivalent to the short FI had
      elapsed without reward. Durations of the short FI and the longer Extinction
      schedules were varied over conditions. In some conditions, the pigeons
      suboptimally responded through the Extinction interval, thus committing the sunk
      time effect. The absolute duration of the short FI had no effect on the choice
      between persisting and escaping. Instead, the ratio of FI and Extinction
      durations determined the likelihood of persistence during extinction. 

PMID- 24565983
TI  - Refining risk stratification for locoregional failure after chemoradiotherapy in
      human papillomavirus-associated oropharyngeal cancer.
AB  - BACKGROUND: To determine whether the addition of molecular and imaging biomarkers
      to established clinical risk factors could help predict locoregional failure
      (LRF) after chemoradiation in human papillomavirus (HPV)-related (+)
      oropharyngeal cancer (OPC) and improve patient selection for locoregional
      treatment de-intensification. METHODS: HPV status was determined for 198
      consecutive patients with stage III/IV OPC treated with definitive chemoradiation
      from 5/2003 to 10/2010. The impact of pre-therapy epidermal growth factor
      receptor (EGFR) overexpression; imaging biomarkers including primary tumor and
      nodal maximum standardized uptake values on FDG-PET, gross tumor volumes, and
      matted nodes; and clinical factors on LRF (including residual disease at adjuvant
      neck dissection) was assessed. RESULTS: Primary tumors were HPV+ in 184 patients
      and HPV-negative in 14. EGFR overexpression was related to HPV-negative status
      and was univariately associated with LRF in the overall population, but was
      neither retained in the multivariate model after adjustment for HPV status, nor
      associated with LRF in HPV+ patients. Similarly, imaging biomarkers were
      univariately associated with LRF, but correlated with T-stage and/or N-stage and
      did not remain predictive in HPV+ patients after adjustment for T4- and N3
      stages, which were the only significant predictors of LRF on multivariate
      analysis. Among HPV+ patients with non-T4- or N3-stages, only minimal smoking was
      associated with decreased LRF. CONCLUSIONS: The prognostic impact of EGFR
      overexpression and imaging biomarkers on LRF was predominantly related to their
      association with HPV-negative status and T- or N-stage, respectively. Among HPV+
      OPC patients treated with uniform chemoradiation, only T4-stage, N3-stage, and
      smoking contributed to risk-stratification for LRF.

PMID- 24565985
TI  - [Acute abdomen secondary to appendiceal intussusception].
AB  - Appendiceal intussusception is a rare condition that can occur at any age. Only a
      few cases have been reported, and most are found during surgery. The therapeutic
      approach is usually surgical, ranging from an appendectomy to a hemicolectomy,
      primarily for biopsy and to rule out possible malignancy. Three cases of children
      under 14 years who underwent surgery for acute abdominal pain located in the
      right iliac fossa are presented; one with preoperative diagnosis by ultrasound,
      and the other two with positive intraoperative findings of intussusception of the
      cecal appendix, with acute appendicitis being histologically confirmed. 

PMID- 24565986
TI  - [Swyer-James-MacLeod syndrome. Two case reports and a clinical review].

PMID- 24565984
TI  - Down regulation of RhoC by microRNA-138 results in de-activation of FAK, Src and
      Erk1/2 signaling pathway in head and neck squamous cell carcinoma.
AB  - OBJECTIVE: RhoC a pro-metastatic oncogene is constitutively active in many head
      and neck squamous cell carcinomas. MicroRNA-138 which possesses a documented
      tumor suppressor function can bind to the 3'UTR of RhoC mRNA and inhibit its
      activity. We hypothesize that miR-138 can inhibit the function of RhoC and
      consequently the activation of downstream target molecules involve in the
      signaling cascade. For this reason we investigated the role of miR-138 in HNSCC.
      METHODS: In vitro studies were carried out to evaluate the role of miR-138 in
      HNSCC cell lines and in primary tumors obtained from HNSCC patients. Real time RT
      PCR, Western blot, cell motility, invasion and colony formation assays were
      performed according to standard procedures. RESULTS: Data obtained by G-LISA and
      real time PCR shows an inverse correlation between RhoC expression and miR-138 in
      HNSCC cell lines. Additionally, we obtained a similar pattern of RhoC and miR-138
      expression in primary tumors from HNSCC patients. Over expression of miR-138 in
      HNSCC lines showed down regulation of RhoC, as well as a decrease in cell
      motility, invasion colony and stress fiber formation. Furthermore, a significant
      down regulation was observed for FAK, Src and Erk(1/2) upon miR-138
      overexpression. CONCLUSION: These findings strongly suggest that the inhibition
      of RhoC can be achieved by over expressing miR-138, which further attenuates the
      downstream signaling cascade leading to cancer progression and survival.
      Moreover, this study for the first time shows that down regulation of FAK, Src
      and Erk(1/2) by miR-138 overexpression is due to inhibition of RhoC in HNSCC.

PMID- 24565987
TI  - [Minor phenotypic variants in patients with acute lymphoblastic leukemia from
      west Mexico].
AB  - INTRODUCTION: Acute lymphoblastic leukemia (ALL) has been associated with an
      excess of minor phenotypic variants (MPV), including common variants and minor
      anomalies, indicative of an altered phenogenesis. The objective of the study was
      to determine the association between MPV and ALL. PATIENTS AND METHODS: In a
      hospital based case-control study, we studied 120 children with ALL (including
      standard and high risk) and 120 healthy children as a control group, matched for
      age and sex, seen in the Hospital Civil de Guadalajara Dr. Juan I. Menchaca
      (Guadalajara, Mexico). In both groups, 28 anthropometric measurements were made,
      as well as a systematic search for 405 MPV, through a physical examination.
      Adjusted odds ratio was estimated (aOR) with its intervening variables by
      logistic regression. The confidence interval was 95% (95%CI). RESULTS:
      Anthropometric signs associated with ALL were: long upper segment (aOR= 2.19,
      95%CI: 1.01-4.76), broad jaw (aOR= 2.62, 95%CI: 1.29-5.30), narrow ears (aOR=
      6.22, 95%CI: 2.60-14.85), and increase in internipple distance (aOR= 2.53, 95%CI:
      1.07-5.98). The hypoplasia mesofacial, broad forehead, small nose, short
      columella, narrow ears, telethelia, Sydney crease (SC), Greek type feet and cafe
      au-lait spots (CALS), had a 3 to 17 times higher frequency in children with ALL.
      By number, an association was found from >=4 MPV (aOR= 2.14, 95%CI: 1.25-3.66,
      P=.004). CONCLUSIONS: From >=4 MPV, an association was found with ALL, suggesting
      prenatal factors in phenogenesis and leukemogenesis. CALS and SC were confirmed
      as MPV in children with ALL.

PMID- 24565988
TI  - Tools to assess tissue quality.
AB  - Biospecimen science has recognized the importance of tissue quality for accurate
      molecular and biomarker analysis and efforts are made to standardize tissue
      procurement, processing and storage conditions of tissue samples. At the same
      time the field has emphasized the lack of standardization of processes between
      different laboratories, the variability inherent in the analytical phase and the
      lack of control over the pre-analytical phase of tissue processing. The problem
      extends back into tissue samples in biorepositories, which are often decades old
      and where documentation about tissue processing might not be available. This
      review highlights pre-analytical variations in tissue handling, processing,
      fixation and storage and emphasizes the effects of these variables on nucleic
      acids and proteins in harvested tissue. Finally current tools for quality control
      regarding molecular or biomarker analysis are summarized and discussed. 

PMID- 24565989
TI  - Indian parliament votes to increase access to morphine.

PMID- 24565990
TI  - High level of serum soluble interleukin-2 receptor at transplantation predicts
      poor outcome of allogeneic stem cell transplantation for adult T cell leukemia.
AB  - The prognosis for adult T cell leukemia/lymphoma (ATL) is very poor, and only
      allogeneic hematopoietic stem cell transplantation (allo-SCT) has been considered
      to be a curative treatment for ATL. In this study, we retrospectively analyzed
      data for patients who had received allo-SCT for ATL in Hokkaido, the northernmost
      island of Japan, to determine prognostic factors. Fifty-six patients with a
      median age of 57 years received allo-SCT. Twenty-eight (50.0%) patients had acute
      type and 22 (46.4%) had lymphoma type. Twenty-three (41.1%) patients received
      allo-SCT in complete remission (CR), whereas the others were in non-CR. Seventeen
      (30.4%) patients received myeloablative conditioning and the others received
      reduced-intensity conditioning. With a median follow-up period of 48 months
      (range, 17 to 134 months), 1-year overall survival (OS) and 5-year OS rates were
      55.4% and 46.1%, respectively. The survival curve reached a plateau at 22 months
      after stem cell transplantation (SCT). Male sex, high level of serum soluble
      interleukin-2 receptor (sIL-2R) at SCT, and non-CR at SCT were determined to be
      significant risk factors for OS. A high level of sIL-2R at SCT was a risk factor
      for poor OS in patients with non-CR at SCT by univariate analysis (P = .02), and
      it remained significant after adjustment by sex (hazard ratio, 2.73 [95%
      confidence interval, 1.07 to 7.90]). A high level of sIL-2R at SCT was also
      determined to be a risk factor for disease progression (P = .02). This region
      wide study showed encouraging results for survival after allo-SCT for ATL and
      demonstrated for the first time that a high level of sIL-2R at SCT predicts worse
      SCT outcome.

PMID- 24565991
TI  - Targeting the IL17 pathway for the prevention of graft-versus-host disease.
AB  - Graft-versus-host disease (GVHD) is still a major complication of allogeneic stem
      cell transplantation (allo-SCT). The pathophysiology of GVHD is a multistep
      process initiated by tissue damage and proinflammatory cytokine cascades induced
      by the pretransplantation conditioning therapy. This eventually results in Th1
      driven tissue damage. However, increasing evidence indicates the involvement of
      IL17-producing T cells in GVHD pathogenesis. Both CD4(+) and CD8(+) IL17
      producing T cells are suspected of initiating the Th1 response and aggravating
      tissue inflammation, resulting in full-blown GVHD. In this review, we discuss the
      involvement of IL17-producing T cells in GVHD and the factors involved in their
      expansion, differentiation, and activation. Different dendritic cell (DC)
      subsets, such as plasmacytoid DCs and DC NK lectin group receptor 1(+) myeloid
      DCs have the capability to stimulate Th/Tc17 responses through the release of
      cytokines. Pivotal cytokines include IL1beta, IL6, IL23, and TGFbeta, which are
      known to drive differentiation and expansion of IL17-producing T cells, and these
      cytokines are highly elevated in patients after allo-SCT. Potent activators of
      these DC subsets are motifs that are released upon tissue damage and microbial
      exposure during allo-SCT. These motifs aggravate the Th/Tc17 response via the
      activation of various pathogen recognition receptors, thereby initiating and
      perpetuating GVHD. A more comprehensive understanding of the factors and DC
      subsets driving the IL17 pathway will result in developing and testing novel
      therapeutic approaches for the prevention of GVHD.

PMID- 24565993
TI  - Preparative regimen dosing for hematopoietic stem cell transplantation in
      patients with chronic kidney disease: analysis of the literature and
      recommendations.
AB  - Hematopoietic stem cell transplantation (HSCT) is a potentially life-saving
      therapy that has traditionally been associated with high treatment-related
      mortality due to direct regimen toxicity and a high incidence of graft-versus
      host disease. Historically, pre-existing renal insufficiency has been considered
      an exclusion criterion for transplantation. The advent of nonmyeloablative
      conditioning regimens as a less toxic modality for treatment has made HSCT more
      accessible to elderly patients and patients with comorbidities, such as renal
      impairment. However, there is no clear standard for how to dose preparative
      regimens for patients with chronic renal impairment who undergo HSCT. This
      article serves as a review of the current literature to provide dosing
      recommendations for commonly used preparative agents in the setting of chronic
      kidney disease, with the aim of providing optimal dosing for this patient
      population. 

PMID- 24565994
TI  - Natural radioactivity in drinking underground waters in Upper Silesia and solid
      wastes produced during treatment.
AB  - Content of (226)Ra, (228)Ra and uranium isotopes in waters from subsurface
      aquifers was studied. The sampling points were chosen for having the elevated
      natural content of iron and manganese. Measurements of radium were made by LSC,
      while uranium was measured by alpha spectrometry. Waste sludge was measured by
      gamma spectrometry and three-stage BCR sequential extraction was performed. Radon
      activity concentration in the air at water treatment plants was determined and
      dose adsorbed by staff was calculated. 

PMID- 24565992
TI  - Late cardiovascular complications after hematopoietic cell transplantation.
AB  - The authors sought to better understand the combined effects of pretransplant,
      transplant, and post-transplant factors in determining risks of serious
      cardiovascular disease after hematopoietic cell transplantation (HCT).
      Hospitalizations and deaths associated with serious cardiovascular outcomes were
      identified among 1379 Washington State residents who received HCT (57% allogeneic
      and 43% autologous) at a single center from 1985 to 2005, survived >= 2 years,
      and followed through 2008. Using a nested case-cohort design, relationships
      (hazard ratios [HRs]) between potential risk factors and outcomes were examined
      among affected survivors and a randomly selected subcohort (N = 509). After 7.0
      years of median follow-up (range, 2.0 to 23.7), the 10-year cumulative incidence
      of ischemic heart disease, cardiomyopathy, stroke, and all-cause cardiovascular
      death was 3.8%, 6.0%, 3.5%, and 3.7%, respectively. In multivariable analysis,
      increased pretransplant anthracycline was associated with cardiomyopathy. Active
      chronic graft-versus-host disease was associated with cardiovascular death (HR,
      4.0; 95% confidence interval, 1.1 to 14.7); risk was otherwise similar between
      autologous versus allogeneic HCT recipients. Independent of therapeutic
      exposures, pretransplant smoking, hypertension, dyslipidemia, diabetes, and
      obesity conferred additional risk of all outcomes except stroke (HR >= 1.5 for
      each additional risk factor, P < .03). Hypertension and dyslipidemia at 1 year
      with persistence of these conditions 2 or more years after HCT also were
      associated with independent risks of multiple outcomes. HCT survivors with
      preexisting or newly developed and persistent cardiovascular risk factors remain
      at greater risk of subsequent serious cardiovascular disease compared with other
      survivors, independent of chemo- and radiotherapy exposures. These survivors
      should receive appropriate follow-up and be considered for primary intervention.

PMID- 24565995
TI  - Family-based association study of ciliary neurotrophic factor receptor and
      norepinephrine transporter genes in attention-deficit hyperactivity disorder.

PMID- 24565997
TI  - A practical approach to the theoretical models to calculate NO parameters of the
      respiratory system.
AB  - Expired nitric oxide (NO) is used as a biomarker in different respiratory
      diseases. The recommended flow rate of 50 mL s-1 (F(E)NO0.05) does not reveal
      from where in the lung NO production originated. Theoretical models of NO
      transfer from the respiratory system, linear or nonlinear approaches, have
      therefore been developed and applied. These models can estimate NO from distal
      lung (alveolar NO) and airways (bronchial flux). The aim of this study was to
      show the limitation in exhaled flow rate for the theoretical models of NO
      production in the respiratory system, linear and nonlinear models. Subjects (n =
      32) exhaled at eight different flow rates between 10-350 mL s-1 for the
      theoretical protocols. Additional subjects (n = 32) exhaled at tree flow rates
      (20, 100 and 350 mL s-1) for the clinical protocol. When alveolar NO is
      calculated using high flow rates with the linear model, correction for axial back
      diffusion becomes negligible, -0.04 ppb and bronchial flux enhanced by 1.27. With
      Hogman and Merilainen algorithm (nonlinear model) the corrections factors can be
      understood to be embedded, and the flow rates to be used are <=20, 100 and >=350
      mL s-1. Applying these flow rates in a clinical setting any F(E)NO can be
      calculated necessitating fewer exhalations. Hence, measured F(E)NO0.05 12.9 (7.2
      18.7) ppb and calculated 12.9 (6.8-18.7) ppb. In conclusion, the only possibility
      to avoid inconsistencies between research groups is to use the measured NO values
      as such in modelling, and apply tight quality control to accuracies in both NO
      concentration and exhaled flow measurements.

PMID- 24565999
TI  - Cloning of the genome of a goose parvovirus vaccine strain SYG61v and rescue of
      infectious virions from recombinant plasmid in embryonated goose eggs.
AB  - The SYG61v is an attenuated goose parvovirus (GPV) that has been used as a
      vaccine strain in China. The genome of SYG61v was sequenced to attempt to
      identify the genetic basis for the attenuation of this strain. The entire genome
      consists of 5102 nucleotides (nts), with four nt deletions compared to that of
      virulent strain B. The inverted terminal repeats (ITR) are 442 nts in length, of
      which 360 nts form a stem region, and 43 nts constitute the bubble region.
      Although mutations were observed throughout the ITR, no mismatch was found in the
      stem. Alignment with other pathogenic GPV strains (B, 82-0321, 06-0329, and YZ99
      5) indicated that there are 10 and 11 amino acid mutations in the Rep1 and VP1
      proteins of SYG61v, respectively. The complete genome of SYG61v was cloned into
      the pBluescript II vector and an infectious plasmid pSYG61v was generated.
      Infectious progeny virus was successfully rescued through transfection of the
      plasmid pSYG61v in embryonated goose eggs and yielded viral titers similar to its
      parental virus, as evaluated by ELD50. 

PMID- 24565998
TI  - Loss of Hand2 in a population of Periostin lineage cells results in pronounced
      bradycardia and neonatal death.
AB  - The Periostin Cre (Postn-Cre) lineage includes endocardial and neural crest
      derived mesenchymal cells of the cardiac cushions, neural crest-derived
      components of the sympathetic and enteric nervous systems, and cardiac
      fibroblasts. In this study, we use the Postn-Cre transgenic allele to
      conditionally ablate Hand2 (H2CKO). We find that Postn-Cre H2CKOs die shortly
      after birth despite a lack of obvious cardiac structural defects. To ascertain
      the cause of death, we performed a detailed comparison of the Postn-Cre lineage
      and Hand2 expression at mid and late stages of embryonic development. Gene
      expression analyses demonstrate that Postn-Cre ablates Hand2 from the adrenal
      medulla as well as the sphenopalatine ganglia of the head. In both cases, Hand2
      loss-of-function dramatically reduces expression of Dopamine Beta Hydroxylase
      (Dbh), a gene encoding a crucial catecholaminergic biosynthetic enzyme.
      Expression of the genes Tyrosine Hydroxylase (Th) and Phenylethanolamine N
      methyltransferase (Pnmt), which also encode essential catecholaminergic enzymes,
      were severely reduced in postnatal adrenal glands. Electrocardiograms demonstrate
      that 3-day postnatal Postn-Cre H2CKO pups exhibit sinus bradycardia. In
      conjunction with the aforementioned gene expression analyses, these results
      strongly suggest that the observed postnatal lethality occurs due to a
      catecholamine deficiency and subsequent heart failure. 

PMID- 24566000
TI  - Sensitive detection of Tomato ringspot virus by real-time TaqMan RT-PCR targeting
      the highly conserved 3'-UTR region.
AB  - A real-time TaqMan RT-PCR assay was developed for the rapid and sensitive
      detection of Tomato ringspot virus (ToRSV), an important plant virus which
      infects a wide range of fruit and ornamental crops. Primers and a probe were
      designed based on the highly conserved 3'-untranslated region (UTR) sequences of
      ToRSV, to amplify a 182bp fragment of this region of RNA-1 and RNA-2. The assay
      was demonstrated to reliably amplify all ToRSV isolates tested. The detection
      limit was estimated to be about 12 copies of the ToRSV target region. No
      amplification was observed from the RNA of other nepoviruses or healthy host
      species. A comparison with a published conventional RT-PCR and a SYBR-based qRT
      PCR indicated that both of the published assays lacked reliability and
      sensitivity, as neither were able to amplify all ToRSV isolates tested, and both
      were approximately 1000 times less sensitive than the novel TaqMan real-time
      assay. This TaqMan real-time assay was tested using four different reagent kits
      and was shown to be robust and stable, with no significant differences in
      sensitivity between kits. It is expected that the implementation of this TaqMan
      real-time RT-PCR assay will facilitate efficient phytosanitary certification of
      nursery stock requiring testing for ToRSV by regulatory agencies, and will also
      have wider uses for the general detection of ToRSV in a range of hosts. 

PMID- 24566001
TI  - Focal changes in diffusivity on apparent diffusion coefficient MR imaging and
      amino acid uptake on PET do not colocalize in nonenhancing low-grade gliomas.
AB  - Low-grade gliomas (LGGs) may harbor malignant foci, which are characterized by
      increased tumor cellularity and angiogenesis. We used diffusion-weighted MR
      imaging (apparent diffusion coefficient [ADC]) and PET with the amino acid O-(2
      (18)F-fluorethyl)-L-tyrosine ((18)F-FET) to search for focal changes of diffusion
      (ADC) and amino acid uptake and to investigate whether focal changes in these
      parameters colocalize within LGGs. METHODS: We retrospectively selected 18
      patients with nonenhancing LGG. All patients had undergone (18)F-FET PET and MR
      imaging for preoperative evaluation or for therapy monitoring in recurrent or
      progressive LGG. Region-of-interest analysis was performed to compare (18)F-FET
      uptake and ADC values in areas with focal intratumoral maximum metabolic activity
      and diffusion restriction and between tumor and normal brain. (18)F-FET uptake
      was normalized to the mean cerebellar uptake (ratio). ADC values were also
      compared with the (18)F-FET uptake on a voxel-by-voxel basis across the whole
      tumor. RESULTS: The mean focal maximum (mean +/- SD, 1.69 +/- 0.85) and global
      (18)F-FET uptake in tumors (1.14 +/- 0.41) exceeded that of normal cortex (0.85
      +/- 0.09) and cerebrospinal fluid (0.82 +/- 0.20). ADC values in the area with
      most restricted diffusion (1.07 +/- 0.22 * 10(-3) mm(2)/s) and in the whole tumor
      (1.38 +/- 0.27 * 10(-3) mm(2)/s) were in the range between normal cortex (0.73 +/
      0.06 * 10(-3) mm(2)/s) and cerebrospinal fluid (2.84 +/- 0.09 * 10(-3) mm(2)/s).
      (18)F-FET uptake did not correlate with corresponding (colocalizing) ADC values,
      either in the area with focal maximum metabolic activity or in the area with most
      restricted diffusion or in the whole tumor. CONCLUSION: There is no congruency
      between (18)F-FET uptake and diffusivity in nonenhancing LGG. Diffusion
      restriction in these tumors most likely represents changes in brain and tumor
      cell densities as well as alteration of water distribution and is probably not
      directly correlated with the density of tumor cells.

PMID- 24566002
TI  - Radiosynthesis and in vivo evaluation of novel radioligands for PET imaging of
      cerebral 5-HT7 receptors.
AB  - The serotonin (5-hydroxytryptamine [5-EtaTau]) 7 receptor (5-HT7R) is the most
      recently discovered 5-HT receptor, and its physiologic and possible
      pathophysiologic roles are not fully elucidated. So far, no suitable 5-HT7R PET
      radioligand is available, thus limiting the investigation of this receptor in the
      living brain. Here, we present the radiosynthesis and in vivo evaluation of Cimbi
      712 (3-{4-[4-(4-methylphenyl)piperazine-1-yl]butyl}p-1,3-dihydro-2H-indol-2-one)
      and Cimbi-717 (3-{4-[4-(3-methoxyphenyl)piperazine-1-yl]butyl}-1,3-dihydro-2H
      indol-2-one) as selective 5-HT7R PET radioligands in the pig brain. The 5-HT7R
      distribution in the postmortem pig brain is also assessed. METHODS: In vitro
      autoradiography with the 5-HT7R selective radioligand (3)H-labeled (R)-3-(2-(2-(4
      methylpiperidin-1-yl)ethyl)pyrrolidine-1-sulfonyl)phenol (SB-269970) was
      performed on pig brain sections to establish the 5-HT7R binding distribution.
      Radiolabeling of 5-HT7R selective compounds was performed in an automated
      synthesis module in which we conducted either palladium-mediated cross coupling
      ((11)C-Cimbi-712) or conventional O-methylation ((11)C-Cimbi-717) using (11)C-MeI
      and (11)C-MeOTf, respectively. After intravenous injection of the radioligands in
      Danish Landrace pigs, the in vivo brain distribution of the ligands was studied.
      Specific binding of (11)C-Cimbi-712 and (11)C-Cimbi717 to 5-HT7R was investigated
      by intravenous administration of SB-269970 before a second PET scan. RESULTS:
      High 5-HT7R density was found in the thalamus and cortical regions of the pig
      brain by autoradiography. The radiosynthesis of both radioligands succeeded after
      optimization efforts (radiochemical yield, ~20%-30% at the end of synthesis).
      Time-activity curves of (11)C-Cimbi-712 and (11)C-Cimbi-717 showed high brain
      uptake and distribution according to 5-HT7R distribution, but the tracer kinetics
      of (11)C-Cimbi-717 were faster than (11)C-Cimbi-712. Both radioligands were
      specific for 5-HT7R, as binding could be blocked by pretreatment with SB-269970
      for (11)C-Cimbi-717 in a dose-dependent fashion. For (11)C-Cimbi-717,
      nondisplaceable binding potentials of 6.4 +/- 1.2 (n = 6) were calculated in the
      thalamus. CONCLUSION: Both (11)C-Cimbi-712 and (11)C-Cimbi-717 generated a
      specific binding in accordance with 5-HT7R distribution and are potential PET
      radioligands for 5-HT7R. (11)C-Cimbi-717 is the better candidate because of the
      more reversible tracer kinetics, and this radioligand showed a dose-dependent
      decline in cerebral binding after receptor blockade. Thus, (11)C-Cimbi-717 is
      currently the most promising radioligand for investigation of 5-HT7R binding in
      the living human brain.

PMID- 24566003
TI  - Interim 18F-FDG PET SUVmax reduction is superior to visual analysis in predicting
      outcome early in Hodgkin lymphoma patients.
AB  - PET performed after 2 cycles of chemotherapy (PET2) allows prediction of outcome
      in most patients with Hodgkin lymphoma (HL). Visual analysis using a 5-point
      scale was proposed to assess PET response, but a semiquantitative approach using
      maximum standardized uptake value (SUVmax) reduction between baseline and interim
      PET was shown to be superior to the 5-point scale in patients with diffuse large
      B-cell lymphoma and may also improve the accuracy of interim PET interpretation
      in HL. To compare the clinical usefulness of both methods in HL patients, we
      analyzed PET2 according to visual and DeltaSUVmax criteria in a retrospective
      single-center study. METHODS: From 2007 to 2010, 59 consecutive patients with a
      first diagnosis of HL were treated with 4-8 cycles of anthracycline-based
      chemotherapy. Radiotherapy was performed in 19 responding patients with localized
      disease. PET was done at baseline (PET0) and after 2 cycles of chemotherapy, and
      treatment was not modified according to the PET2 result. PET2 was interpreted
      using the 5-point scale (positivity for score 4 or 5). The SUVmax reduction
      between PET0 and PET2 (DeltaSUVmax) was computed for all patients, and patients
      with a DeltaSUVmax greater than 71% were considered good responders. RESULTS:
      When the 5-point scale was used, 46 patients (78%) achieved a negative PET2
      result, 7 of whom failed treatment (negative predictive value, 85%). Forty-nine
      patients (83%) had a DeltaSUVmax greater than 71%, 6 of whom failed treatment
      (negative predictive value, 88%). The PET2 positive predictive value was
      significantly better for DeltaSUVmax (70%) than for the 5-point scale (46%). When
      DeltaSUVmax was used, 6 (46%) of the 13 PET2-positive patients could be
      reclassified as good responders. Although visual PET2 positivity was related to a
      lower 4-y progression-free survival (45%) compared with PET2 negativity (81%, P <
      0.002), DeltaSUVmax (>71 vs <=71%) was more accurate for identifying patients
      with different 4-y progression-free survivals (82% vs. 30%; P < 0.0001). In
      multivariate analysis using the international prognosis score and DeltaSUVmax as
      covariates, DeltaSUVmax remained the unique independent predictor for progression
      free survival (P = 0.0001; relative risk, 8.1). CONCLUSION: Semiquantitative
      analysis was more accurate than visual analysis based on the 5-point scale to
      interpret PET2 and predict the outcome of HL patients. These encouraging results
      warrant further confirmation in larger and prospective series.

PMID- 24566004
TI  - Combined effects of collagen type I alpha1 (COL1A1) Sp1 polymorphism and
      osteoporosis risk factors on bone mineral density in Turkish postmenopausal
      women.
AB  - Identification of risk factors for osteoporosis has been essential for
      understanding the development of osteoporosis. The collagen type I alpha1
      (COL1A1) gene is suggested to be implicated in reduced bone mineral density (BMD)
      in osteoporosis. In the present study, the investigation of the effects of Sp1
      polymorphic variants of COL1A1 gene on BMD values, and the determination of the
      association between COL1A1 Sp1 gene variants and osteoporosis risk factors in the
      context of gene-environment interaction in Turkish postmenopausal women were
      aimed. For the detection of COL1A1 Sp1 polymorphism, PCR-RFLP techniques have
      been used. BMD for lumbar spine (L1-L4) and hip (femoral neck and total hip) was
      measured by DXA. This study was carried out using a sample of 254 postmenopausal
      women. We observed a trend decrease in BMD values in the subjects with "ss"
      genotype having lower BMD of lumbar spine, femoral neck and total hip than those
      with "SS" and "Ss" genotype, however the differences did not reach statistical
      significance (P>0.05). We also found that the frequencies of the BMD under mean
      values at the femoral neck (57.5%) and total hip (76.2%) increased considerably
      in the subjects carrying "Ss/ss" genotypes in combination of having family
      history of osteoporosis (61.5% for femoral neck) and smoking history (90.0% for
      total hip). This population-based study indicates that COL1A1 Sp1 polymorphism
      may contribute to the development of osteoporosis in combination of osteoporosis
      risk factors in Turkish postmenopausal women. 

PMID- 24566005
TI  - Cloning, characterization, and heterologous expression of a novel
      glucosyltransferase gene from sophorolipid-producing Candida bombicola.
AB  - Candida bombicola is well-studied for the production of a biosurfactant, the
      sophorolipids. In this paper, the cloning of a glucosyltransferase gene using
      polymerase-chain-reaction (PCR) technique is described. Degenerative primer-pairs
      were first designed based on the highly conserved amino-acid sequences of several
      selected yeast glucosyltransferases. Using these primers, an amplified sequence
      (amplicon) of 700 base-pair from C. bombicola was obtained and subsequently
      sequenced. Based on the sequence of this amplicon, additional target-specific PCR
      primers were designed for use in subsequent rounds of 3'- and 5'-extension using
      DNA walking technique to eventually obtain a C. bombicola genomic sequence
      containing an open-reading-frame putatively identified as a glucosyltransferase
      (gtf-1). The gene was subcloned in Saccharomyces cerevisiae for expression and
      functional characterization. Quantitative RT-PCR confirmed the expression of gtf
      1 in the recombinant S. cerevisiae. In vitro assay with the sonicated cells of
      the recombinant yeast confirms the presence of glucosylation activity on sterol
      and hydroxy fatty acid substrates. This study reports for the first time the
      cloning and characterization of a broad-specificity lipid glucosylation gene from
      C. bombicola, and the functional activity of its gene product. 

PMID- 24566007
TI  - When children are better (or at least more open-minded) learners than adults:
      developmental differences in learning the forms of causal relationships.
AB  - Children learn causal relationships quickly and make far-reaching causal
      inferences from what they observe. Acquiring abstract causal principles that
      allow generalization across different causal relationships could support these
      abilities. We examine children's ability to acquire abstract knowledge about the
      forms of causal relationships and show that in some cases they learn better than
      adults. Adults and 4- and 5-year-old children saw events suggesting that a causal
      relationship took one of two different forms, and their generalization to a new
      set of objects was then tested. One form was a more typical disjunctive
      relationship; the other was a more unusual conjunctive relationship. Participants
      were asked to both judge the causal efficacy of the objects and to design actions
      to generate or prevent an effect. Our results show that children can learn the
      abstract properties of causal relationships using only a handful of events.
      Moreover, children were more likely than adults to generalize the unusual
      conjunctive relationship, suggesting that they are less biased by prior
      assumptions and pay more attention to current evidence. These results are
      consistent with the predictions of a hierarchical Bayesian model. 

PMID- 24566006
TI  - Anti-amyloidogenic effects of ID1201, the ethanolic extract of the fruits of
      Melia toosendan, through activation of the phosphatidylinositol 3-kinase/Akt
      pathway.
AB  - Amyloid beta (Abeta) peptides, which are generated from amyloid precursor protein
      (APP), are thought to play a major role in the pathogenesis of Alzheimer's
      disease (AD). This study investigated the anti-amyloidogenic effects of the
      ethanolic extract of Meliae Fructus (ID1201) using human embryonic kidney 293
      cells with stably expressed human wild-type or Swedish mutant APP695 and beta
      secretase 1. ID1201 treatment enhanced the non-amyloidogenic metabolism of APP;
      increases in soluble APPalpha levels and decreases in soluble APPbeta and Abeta
      levels resulted from the alpha-secretase activation through the
      phosphatidylinositol 3-kinase (PI3K)/Akt pathway. In addition, ID1201-treated
      5*familial AD (FAD) mice with 5 mutations in APP and presenilin 1 showed reduced
      levels of Abeta and amyloid plaques in the brain relative to those of 5*FAD mice
      with vehicle treatments. These results indicate that ID1201 possesses anti
      amyloidogenic effects via the activation of the PI3K/Akt pathway, suggesting that
      it is a potential therapeutic agent for AD. 

PMID- 24566008
TI  - Early inhaled nitric oxide at high dose enhances rat lung development after
      birth.
AB  - RATIONAL: Inhaled nitric oxide (NO) is frequently administered to full term and
      preterm newborns in various clinical settings in order to alleviate pulmonary
      hypertension whilst improving oxygenation. However, the physiological effect of
      NO on early postnatal lung development has not yet been clearly described. We
      therefore investigated whether NO administered by inhalation affects lung
      development at early postnatal life. METHODS: Pregnant rats were placed in a
      chamber containing 5 ppm (iNO-5 ppm group) and 20 ppm NO (iNO-20 ppm group),
      started from the last day of their pregnancy in order to keep rat pups under
      ambient NO from birth to 7 days postnatal. Control animals were kept at room air
      and all rat pups were sacrificed at postnatal day 7 and day 14. RESULTS: Lung-to
      body weight and wet-to-dry lung weight ratios did not significantly differ among
      3 groups at postnatal day 7 and day 14. Vascular volume densities (Vv) in both NO
      groups (5 and 20 ppm) were higher than controls (P<0.05; P<0.001). Pulmonary
      vessel number was significantly increased in iNO-20 ppm group. Radial alveolar
      counts (RAC) and mean linear intercepts (MLI) markedly increased (consistent with
      increased alveolarization) in iNO-20 ppm group. This was associated with
      upregulation of VEGF/VEGFR-2, MT1-MMP/MMP2 and HO-1 protein expression in iNO-20
      ppm group. CONCLUSIONS: We concluded that inhaled NO at 20 ppm enhanced lung
      development possibly through increased expression of HO-1, VEGF/VEGFR-2, and MMP2
      at early stage of postnatal rat life.

PMID- 24566010
TI  - Atherosclerosis of coronary blood vessels - local or systemic inflamation?
AB  - The presence of atherosclerotic lesions in the blood vessels is a predisposition
      for the development and occurrence of acute ischaemic attacks. Bigger
      atherosclerotic lesions in the coronary blood vessels cause lumen occlusion,
      which is a cause of acute myocardial infarction. Endothelial dysfunction is
      defined as an ability of the endothelium to produce vasorelaxing nitric oxide
      (NO), or deregulation of the other vasoactive substances, such as angiotensin II
      and endothelin [13]. This definition describes endothelial dysfunction as an
      improper vasomotor constriction of the vessel, that leads to lumen occlusion of
      the already existing atherosclerotic lesions. According to the modern model, the
      development of atherosclerotic plaque and inappropriate endothelial NO production
      have a synergistic role in patho-physiological and molecular processes in the
      blood vessels [14]. Lesions in the coronary arteries are deposits of huge
      quantities of foamy cells and fibrous plaques. The thin fibrous plaques are 10
      20% of the total plaque population and are the cause of 80-90% of clinical cases
      due to their ability to rupture [48]. According to all the results from published
      studies by far, it has been pointed out that the plaque stability, not the
      absolute size influences the rupture potential. Elucidating the risk factors that
      may modify in the atherogenesis and the consequent atherothrombic effect is the
      first step to this goal.

PMID- 24566009
TI  - Hepatitis C virus (HCV)-specific memory B-cell responses in transiently and
      chronically infected HIV positive individuals.
AB  - BACKGROUND: Antibody responses to hepatitis C virus (HCV) occur delayed and
      overly decline after viral clearance indicating that the B-cell response to HCV
      is abnormal. Virus-specific memory B-cells have recently been found in infected
      individuals, but the viral exposure requirements for the generation of these
      cells is unknown. OBJECTIVES: The primary goal of this study was to quantify and
      compare the HCV-specific memory B-cell response between chronic and resolved HCV
      infected individuals. A secondary goal was to examine if HIV-specific memory B
      cell responses are maintained during HCV co-infection. STUDY DESIGN: HCV core
      protein- and HIV-specific memory B-cell responses were examined in HIV/HCV
      infected individuals treated 4-30 weeks after HCV diagnosis. Memory B-cell
      frequencies were compared between chronically and transiently infected
      individuals. RESULTS: Chronically infected individuals had vigorous HCV-specific
      memory B-cell responses and antibodies, whereas subjects with transient viremia
      showed low or undetectable virus-specific B-cell responses. In addition,
      chronically HIV/HCV-infected subjects had robust HIV-specific memory B-cell
      responses. CONCLUSIONS: Whereas chronic HCV infection induces virus-specific
      antibodies and memory B-cells, transient infection in individuals with sustained
      viral response to therapy does not stimulate a durable HCV-specific B-cell
      response indicating that the formation of long-lived virus-specific B-cells is
      suppressed in the early phase of infection. This may contribute to the inability
      to spontaneously clear HCV infection.

PMID- 24566011
TI  - Transradial approach as first choice for stenting of chronic total occlusion of
      iliac and femoral superficial artery.
AB  - The transradial approach (TRA) for treatment of aortoiliac occlusive disease
      (AIOD) is nowdays a more common approach than several years ago. This is due to
      less post-procedural bleeding complications and its impact on mortality. The main
      reason for the growing interest in the TRA is because of the safety profile of
      this access. Peripheral arterial disease (PAD) is a growing phenomenon. It is a
      common circulatory problem in which narrowed arteries reduce blood flow to lower
      extremities due to atherosclerotic arterial lesions. According to the Trans
      Atlantic Inter-Society Consensus on the Management of Peripheral Arterial Disease
      (TASC II), an endovascular approach is recommended in type A and B lesions, and
      an open surgical approach for type C and D lesions. The aim of the study is to
      put the accent on the advantages of the transradial approach (TRA) versus the
      transfemoral approach (TFA), its safety and efficacy in treating peripheral
      arterial disease (PAD) even in type C and D lesions, in well and properly
      selected patients on whom it may be performed, and to evaluate the outcomes of
      transradial iliac stenting (TRAIS), attempting to increase the demand for the new
      devices and tools for its treatment. These improvements will exclude some
      disadvantages and limitations of TRA in the field of endovascular peripheral
      interventions (distance from the puncture site to the lesion location, bigger
      support, thinner devices). Despite difficult lesions, TASC C/D, the overall
      primary procedural and technical success rate was 100%. The ankle brachial index
      (ABI) significantly improved from a mean of 0.46 to 0.90 and 0.94 on the six
      months follow-up. Angiographic estimated residual stenosis was 0%. No minor or
      major complications (haematoma, distal emboli, vessel dissection, rupture, death)
      were documented. The primary patency rate was 100% for the iliac and for the SFA.
      The secondary patency rate after 6 months follow-up was also 100%. Transradial
      access might be recommended as the first-choice vascular access site for
      interventions on the iliac, and even proximal femoral territories. This technique
      is still limited by the lack of adequate equipment. This issue should be overcome
      in the future.

PMID- 24566012
TI  - Total dialysate calcium effects on calcium balance during dialysis.
AB  - INTRODUCTION: Total dialysate calcium concentration has an important influence on
      calcium metabolism in bicarbonate high-flux dialysis. The aim of the study is to
      investigate the influence of different dialysate calcium concentrations on serum
      concentration of ionised calcium and on the balance of total dialysate calcium.
      MATERIALS AND METHODS: A total of 20 stable aneuric patients on chronic
      bicarbonate high-flux haemodialysis with a frequency of 4 hours, 3 times per week
      with two different concentrations of total dialysate calcium (tdCa) were included
      in the study. Dialysis in the first session was performed with total dialysate
      calcium of 1.25 mmol/L, and at the next session with dialysate calcium of 1.5
      mmol/L. The serum concentrations of total and ionized calcium were determined
      before and after each dialysis session. The balance of total dialysate calcium
      was measured on the dialysate side. RESULTS: Serum concentration of total calcium
      before and after haemodialysis did not show any significant difference in HD with
      a total dialysate calcium of 1.25 mmol/L (2.40 +/- 0.19 mmol/L before HD and 2.46
      +/- 0.15 mmol/L after HD). Serum ionized calcium in HD with tdCa 1.25
      significantly decreased after HD (1.16 +/- 0.09 mmol/L before HD to 1.08 +/- 0.04
      mmol/after HD, p < 0.05). The total serum calcium significantly increased after
      HD in comparison to HD with tdCa of 1.5 mmol/L (2.40 +/- 0.15 mmol/L to 2.65 +/-
      0.16 mmol/L, p < 0.05). The concentration of serum ionized calcium did not
      increase significantly in HD with tdCa 1.50 mmol/L (1.16 +/- 0.08 mmol/L to 1.20
      +/- 0.05 mmol/L). Average values of total dialysate calcium balance (gradient of
      diffusion between dialysate and patient) were negative in tdCa 1.25 (1.38 +/-
      0.08 mmol/L versus 1.48 +/- 0.43 mmol/L), but in HD with tdCa 1.5 were slightly
      positive (1.56 +/- 0.07 mmol/L versus 1.52 +/- 0.07). CONCLUSION: The use of
      total dialysate calcium of 1.5 mmol/L is beneficial because balance values of
      total dialysate calcium are slightly positive, but serum concentration of ionized
      calcium stays in the normal range.

PMID- 24566013
TI  - Are Macedonian chronic patients alexithymic?
AB  - Psychological factors have been supposed as an important link in the chain of
      pathogenesis and the course of many diseases, especially stress-related ones. The
      field of psychosomatics is concerned with the study of the mind / body relations
      and, in this context, to the assessment of the influence of psychological factors
      on bodily changes and, consequently, with the development of illness.
      Alexithymia, the inability to identify or label emotions, has been shown to be
      associated with patients with many chronic conditions. The study was performed to
      obtain a) normal values of TAS-20 in Macedonian healthy people and b) to compare
      the results with a groups of chronic patients. In this study, TAS-20 was applied
      as a measure of alexithymia. It was concluded that the alexithymia construct is a
      permanent personality trait related to neurobiological brain specifics. The
      construct is important for both, either as a trigger or as the conesquence of the
      illness. Patients with chronic diseases are more alexithymic than healthy people.
      In our research alexithymia has been confirmed in patients with cancer,
      rheumatoid arthritis and dialyzed patients as well as in patients after
      myocardial infarction. An alexithymia construct can influence the prognosis and
      outcome of the chronic disease. Anyhow, the psychological support for mediating
      alexithymia should be included in the therapeutic protocols of all chronic
      patients.

PMID- 24566014
TI  - Multivariable model consisting of clinical and biological markers for time to
      first treatment in CLL patients: Preliminary results from single centre
      experience.
AB  - INTRODUCTION: The clinical course for patients with chronic lymphocytic leukaemia
      (CLL) is extremely heterogeneous; one of the most important challenges in the
      clinical management of these patients is the decision on initiating their
      treatment, but there is no available prognostic system that will resolve this
      issue. Usually, criteria for active disease are used to initiate therapy.
      Recently, some authors have proposed prognostic models, scoring systems involving
      a set of clinical and biological risk factors and estimates of individual patient
      survivals. Here, we report our initial results from a study designed to evaluate
      the statistical association of the distinct clinical and biological parameters
      with the prognosis and time to initiating treatment for patients with CLL.
      MATERIAL AND METHODS: Our study incorporated 100 consecutive, treatment naive CLL
      patients. In each patient all traditional laboratory, clinical and biological
      prognostic factors were evaluated at their first visit to our Institution. We
      then combined the following independent characteristics: age, beta-2
      microglobulin, absolute lymphocyte count, sex, Rai stage, and number of involved
      lymph node groups, which are included in some of the already published CLL
      prognostics index, in association with the CD38 expression and mutational status
      of the immunoglobulin heavy chain gene variable region (IGVH). Further, we
      correlated those factors by multivariable analysis with time to first treatment.
      This multivariable model was used to develop a nomogram-a weighted tool to
      calculate 5- and 10-year survival probability and estimate median time to first
      treatment (TFT). RESULTS: According to the prognostic index, a classification
      tree was built that identified three subsets of patients whose scores were 1-3
      (low risk - 32 pts - 32%), 4-7 (intermediate risk - 48 pts - 48%) and > 8 (high
      risk - 20 pts - 20%). Estimated median survival in the low risk subset of
      patients is 141 years, and 10.7 and 4.6 years respectively in the intermediate
      and high risk subsets of patients. Projected survival in respectively low,
      intermediate and high-risk groups are 100%, 100%, 25%, and 43%, 34%, 25% at 5
      years and 10 years, respectively. Also, statistical analyses showed that among
      other things CD38 expression and unmutated IGHV mutation status are associated
      with a shorter time to first treatment. CONCLUSION: Our prognostic model that
      combines and correlates the distinct clinical and biological markers of CLL
      patients enables identification of patients who are at high risk of progression.
      This prognostic model may facilitate the clinical decision for initiating
      treatment.

PMID- 24566015
TI  - Epidemiological analysis of progression-free survival (PFS) and overall survival
      (OS) in non-small-cell lung cancer patients in Republic of Macedonia.
AB  - Lung cancer represents the leading cause of cancer mortality worldwide,
      accounting for ~1.2 million deaths each year. Improving survival in lung cancer
      is a major challenge for modern oncology considering that 5-year survival remains
      < 15%, across all stages of the disease with < 7% of patients alive 10 years
      after diagnosis. About 85% to 90% of lung cancers are non-small-cell lung cancer
      (NSCLC). Lung cancer is the leading cause of cancer-related mortality in
      Macedonia with more than 900 newly diagnosed lung cancer patients per year. The
      motive for undertaking the study was precisely the lack of adequate statistical
      data on treatment outcomes and survival rates of non-smal-cell lung cancer
      patients in the country. The main goal was to provide an assessment of
      progression-free survival and overall survival in NSCLC patients treated at UCRO
      Skopje, over the past three years: 2009-2011. The research represents a follow-up
      study. The study was based on filling in forms for an epidemiological analysis of
      PFS and OS in NSCLC patients. These forms contain demographic, clinical and
      histological data, as well as dates of diagnosis, treatment initiation and
      outcomes. Data were collected from patient files for a period of three years
      (2009-2011), collected through the registration of each NSCLC patient treated in
      the period of the investigation. The statistical series were analysed by
      determining the ratio, proportions, chi-square and Student t-test and survival
      analysis. The study included 1002 patients with NSCLC treated at the UCRO, of
      whom 859 were males and 137 were females, and 0.6% missing data for gender. The
      average age of patients was 60.4 +/- 9.0 y., min. of 19 y., max. of 85 y. Most of
      the patients were smokers- 86.9%. The dominant stage in NSCLC was stage IV, with
      36.3%, followed by IIIA 17.5%, stages IIIB and IIB with 13.6% and so on. In the
      examined group of patients the most common subtype was 56.9% with planocellular,
      28.2% with adenocarcinoma, large-cell with 7.7% and missing / no closer subtype
      7.2%. Median survival from diagnosis to the last check-up/death was 6.2 m. 25% of
      patients with NSCLC from diagnosis to the last check-up/death died in the first
      2.5 m and 25% survived more than 11.1 m. Median survival from treatment outset to
      the last check-up/death was 5.4 m. 25% of patients with NSCLC survived for two
      months from the outset of treatment to the last check-up/death and 25% survived
      for more than 10.8 m. In the course of the study we found that the median
      survival in 2009, 2010 and 2011 differed from the diagnosis to the last
      control/death. In 2009, median survival was 7.5 m and we registered a
      statistically significantly longer survival compared to 2010 - 6.1 m, and 2011 -
      5.4 m. Similar data and conclusions were received in calculating the survival
      from therapy to the last check-up/death. Median survival in 2009 was 6.2 m and
      this is a statistically significant longer survival compared with 2010 (5.9 m)
      and 2011 (4.6 m). The results indicate that compared with international data
      patients with NSCLC had a shorter life of survival.We hope that this study will
      help to improve the future treatment of non-small-cell lung cancer patients
      through optimizing the treatment for every single patient, which will help in
      longer patient survival. Precise determination of these data provides for a
      proper selection of the best treatment option and optimized therapy for every
      patient.

PMID- 24566016
TI  - Computed tomography or magnetic resonance imaging - our experiences in
      determining preoperative TNM staging of bladder cancer.
AB  - Bladder cancer is the ninth most common cancer diagnosis worldwide. Early
      detection of bladder cancer is important, since up to 47% of bladder cancer
      related deaths might be avoided. AIM: To show our experience in determining the
      staging of bladder cancer with multidetector computed tomography (MDCT) and
      magnetic resonance imaging (MRI), making comparison of stage accuracy with
      contrast enhanced MDCT, conventional MR imaging and dynamic contrast-enhanced MR
      imaging on the one hand and pathoistological diagnoses after transurethral
      resection of the non-muscle invasive bladder cancers or radical cystectomy for
      patients with muscle-invasive bladder cancers. MATERIALS AND METHODS: Ninety
      patients with histologically proved bladder cancer were prospectively examined
      with MDCT, conventional and dynamic MR imaging before tumour resection. RESULTS:
      Staging was correct in 55.6% with CT, 56.7% with conventional MRI and in 86.7%
      with dynamic MRI, which was highly significant compared with CT and conventional
      MRI. Overestimation for superficial tumors was high with CT (31.25%) and
      conventional MR imaging (25%), but was significantly reduced with dynamic MR
      imaging (8.3%). The percentages of underestimation in surgically proved invasive
      tumours (pT2- pT4) were lowest with dynamic MR imaging. CONCLUSION: CT and MR
      imaging are less accurate in the evaluation of the depth of mural invasion and
      for both techniques overstaging is the most frequent error. Dynamic contrast
      enhanced MRI with 87% of accuracy, 8.3% overestimation for superficial tumours
      and lowest underestimation for invasive tumours, make this imaging considerably
      more accurate.

PMID- 24566017
TI  - Impact of socio-demographic factors on the delayed diagnosis and advanced stage
      presentation of patients with invasive cervical cancer in Macedonia.
AB  - AIM: The study aims to establish certain socio-demographic factors associated
      with delayed presentation (i.e. advanced stage at diagnosis) in patients with
      invasive cervical cancer in Macedonia. MATERIALS AND METHODS: The cross-sectional
      study was conducted with patients already diagnosed and treated for invasive
      cancer of the uterine cervix who came in for their regular annual check-up at the
      University Radiotherapy and Oncology Clinic, Medical Faculty, Ss. Cyril and
      Methodius University in Skopje, Macedonia. The data were collected by
      interviewing the participants using a standardized questionnaire. RESULTS: A
      total of 115 patients were recruited in the study. Eight of them were excluded
      from further analysis due to incomplete data. Close to 72% of the patients
      analysed presented with advanced stage disease, while 28.04% of the patients were
      diagnosed with early stage disease. The univariate analysis and Chi-square
      statistics showed that the patients had a higher probability of being diagnosed
      with advanced stage disease if they had a low monthly income (p = 0.01), had
      lower degrees of education (p < 0.001), had an unsatisfactory level of genital
      hygiene (p < 0.001) and had no family history of invasive cervical cancer in
      first degree female relatives (p = 0.003). DISCUSSION: The results from the study
      could be utilized to identify the population at risk which should be targeted for
      implementation of specialized educational programmes for familiarizing the
      population with the nature of the disease which in turn would increase the level
      of consciousness as a step towards implementing a national screening programme.

PMID- 24566018
TI  - Comparative analysis of diagnostic methods in meniscal lesions.
AB  - The aim of this study is to determine the accuracy of clinical and MRI diagnosis
      in comparison with arthroscopy for detection of meniscal lesions. Also, to answer
      if MRI diagnosis impacts on the decision of the surgeon for the choice of
      treatment (operative or conservative). MATERIAL AND METHODS: We examined 70
      patients with knee injuries. Clinical diagnosis was established using the case
      history of the patient and positive clinical tests for meniscal injuries
      (McMurray and Aplay). All patients underwent MRI on a 1.5 T magnet for MRI
      diagnosis. This was followed by arthroscopy for final diagnosis. Clinical and MRI
      diagnoses were correlated with the arthroscopic diagnosis which was used as a
      gold standard. RESULTS: Of 70 patients with knee injuries, 55 had a clinical
      diagnosis of meniscal lesions out of whom 44 patients had a medial meniscal
      lesion and 11 had a lateral meniscal lesion. Arthroscopy confirmed the clinical
      diagnosis in 32 patients (72.72%) (44 vs 32) in medial meniscal lesion, and 8
      patients (72.7%) (11 vs 8) with a lateral meniscal lesion. In MRI diagnosis of 56
      patients with medial meniscal lesion arthroscopy confirmed the diagnosis in 34
      patients (60.7%) (56 vs 34) and pf 10 patients with lateral meniscal lesion
      arthroscopy confirmed the diagnosis in 6 patients (60%) (10 vs 6). The
      sensitivity, specificity, PPV and NPV of clinical diagnosis versus MRI for medial
      meniscus were (79.9% vs 79.5%); (58.1% vs 38.1%); (69.8% vs 69.6%); (69.2% vs
      69.2%). The sensitivity, specificity, PPV and NPV of clinical diagnosis versus
      MRI for lateral meniscus were (50% vs 40%); (92.7% vs 92.7%); (63.6% vs 60%);
      (87.9% vs 85.5%). CONCLUSIONS: Carefully performed clinical examination can give
      an equal or better diagnosis of meniscal lesions in comparison with MRI
      diagnosis. Any experienced orthopaedic surgeon can trust his clinical diagnosis
      as an indication of arthroscopy. When the clinical diagnosis is established, with
      no doubts due to positivity of the clinical tests, the MRI is not essential. In
      suspected cases where there is a dilemma, MRI is very helpful in making a
      decision for arthroscopy. The diagnostic accuracy of clinical and MRI diagnosis
      of meniscal lesions is high. Their reliability in diagnosing meniscal lesions is
      evident. lesion, clinical diagnosis, MRI, arthroscopy.

PMID- 24566019
TI  - Oral findings in end-stage renal disease.
AB  - The aim of the study was to analyse and compare the most frequent clinical oral
      symptoms, signs and lesions at end-stage renal disease (ESRD), before kidney
      transplantation (BKT) and after kidney transplantation (AKT). A total of 35
      subjects with ESRD were included, 19 in group A (BKT) and 16 in group B (AKT).
      Oral lesions were classified according to referent clinical diagnostic criteria:
      Serum albumins, urea, creatinine and salivary urea, creatinine uremic acid were
      determined by standard biochemical spectrophotometric methods (Human, Germany).
      For serum albumin concentration measurement (g/L) the method of bromcresol green
      assay was used while serum and salivary uric acid determination (umol/L) was
      performed according the uricase/PAP method. Serum creatinine concentration was
      measured (umol/L) with the Jaffe kinetics method, without deproteinization. Oral
      signs, symptoms and lesions were higher in group A: metallic taste (O.R. = 6.61/
      +/- 95% CI : 1.13 < O.R. < 38.69), dry mouth (O.R. = 30/ +/- 95% CI : 3.15 < O.R.
      < 285.71), uremic stomatitis (O.R. = 6.5/ +/- 95% CI : 1.47 < O.R. < 28.80 and
      coated tongue (O.R. = 11.73/ +/- 95% CI : 2.31 < O.R. < 59.54). On the other
      hand, in group B, gingival enlargement (O.R. = 59.5/ +/- 95% CI : 7.41 < O.R. <
      478.05) was more common. High statistically significant differences were recorded
      between group A and B for dry mouth and gingival enlargement (p > 0.001). Blood
      urea, creatinine and albumin levels, as well as salivary urea creatinine and
      uraemic acid values, were significantly higher in group A. Chances of the
      appearance of all symptoms, clinical signs and lesions, except gingival
      enlargement, were greater in group A as against group B. Some of our findings
      correspond with the stage of the disease and some with the use of medicaments in
      treatment.

PMID- 24566020
TI  - Anxiety and personality characteristics in children undergoing dental
      interventions.
AB  - Anxiety about and fear of dental treatment have been recognized as sources of
      problems in the management of child dental patients. It has been suggested that
      some individuals who are fearful of or anxious about dental treatment have a
      constitutional vulnerability to anxiety disorders as is evidenced by the presence
      of multiple fears, generalized anxiety or panic disorders. Concerning the child
      population, maternal anxiety is considered to be a major factor affecting the
      behaviour of young children expecting dental intervention. The aim of the study
      was to the measure general anxiety of children undergoing dental intervention and
      to compare it with some personality characteristics, such as psychopathology,
      extroversion and neuroticism. The evaluated sample comprises 50 children (31
      girls and 19 boys), randomly selected at the University Dental Hospital, Skopje.
      The mean age for girls was 11.4 (+/- 2.4) years, and for boys 10.7 (+/- 2.6)
      years. Two psychometric instruments were used: the General Anxiety Scale for
      Children (GASC) and the Eysenck Personality Questionnaire (EPQ). The study
      confirms the presence of a high anxiety level (evaluated with GASC) among all
      children undergoing dental intervention. It also confirmed differences in anxiety
      scores between girls and boys, girls having higher scores for anxiety.
      Personality characteristics (evaluated with EPQ) showed low psychopathological
      traits, moderate extroversion and neuroticism, but accentuated insincerity
      (evaluated with L scale). L scales are lower with increasing age, but P scores
      rise with age, which could be related to puberty. No correlation was found
      between personality traits (obtained scores for EPQ) and anxiety except for
      neuroticism, which is positively correlated with the level of anxiety. In the
      management of dental anxiety some response measures (psychological support,
      biofeedback, and relaxation techniques) are recommended.

PMID- 24566021
TI  - Technology and the use of acrylics for provisional dentine protection.
AB  - Acrylics are compounds polymerized from monomers of acrylic, metacrylic acid or
      acrylonitrates. The purpose of this paper is to present the technology and use of
      acrylics for provisional dentine protection in the practice of dental
      prosthodontics. For this reason, we followed 120 clinical cases from the everyday
      clinical practice, divided into 4 groups of 30 patients who needed prosthetic
      reconstruction. The first group included cases in which we applied celluloid
      crowns for dentine protection, for the second group we used acrylic teeth from a
      set of teeth for complete dentures; in the third and fourth groups the
      fabrication was done with the system of an impression matrix and the acrylic
      resin block technique respectively. In all the examined patients, the gingival
      index by Silness and Loe and the vitality of the dental pulp were verified
      clinically, after preparation and 8 days from the placement of the provisional
      crown. The value for dental sensitivity measured after preparation was 2.59, and
      8 days after the placement of the provisional crown it bwas 3.1. From these
      results we can conclude that after the 8th day from the placement of the
      provisional crown, there was an adaptation period, characterized by a decrease in
      the painful sensations. The value of the Silness and Loe gingival index measured
      after the preparation was 1.34, and 8 days from the placement of the provisional
      crown was 0.94. The results inclined us to the fact that the provisional acrylic
      crowns facilitated the reparation of the periodontal tissue.

PMID- 24566022
TI  - Doctors and lecturers from Macedonia elected for the first time to the Faculty of
      Medicine in Skopje in the period 1955-60.
AB  - AIM: To present a group of young doctors from Macedonia who were elected as
      lecturers at the Faculty of Medicine in Skopje, Macedonia, in the period 1955-60.
      METHOD: A retrospective study based on archive materials, encyclopaedias and
      jubilee publications of the Faculty of Medicine and Faculty of Dentistry in
      Skopje, other relevant sources of information, and a review of the relevant
      literature. RESULTS: The Faculty of Medicine in Skopje was founded in 1947 and
      the first meeting of the Teachers' Council of the Faculty was held on March 17,
      1947. The first generation of 153 students was enrolled in the autumn of 1947 and
      the first lecture was delivered on November 3, 1947. Besides 15 doctors from
      Macedonia - faculty staff, who had been appointed in the period from 1947-54 and
      contributed to the establishment and initial development of the Faculty of
      Medicine in Skopje, an additional group of 23 lecturers from Macedonia was
      elected in the period from 1955-60. Those 38 pioneers and coryphaei of medicine
      in Macedonia played important roles in the establishing and/or further
      development of a number of the faculty departments/chairs, institutes and clinics
      within the newly established Faculty of Medicine in Skopje in 1947 and in the
      first 10-15 years of its initial development, until 1960 and later. CONCLUSION:
      The Faculty of Medicine in Skopje, founded in 1947, played a crucial role in the
      education of medical professionals, in improving the poor health status of the
      population and the overall further development of the health system and provision
      of health care to the population of Macedonia. The contribution of the second
      group of 23 doctors and lecturers from Macedonia in furthering the development of
      the Faculty of Medicine in Skopje, during the 1950s and later, was very
      important.

PMID- 24566023
TI  - US thyroid cancer rates are epidemic of diagnosis not disease, study says.

PMID- 24566024
TI  - [Idiopathic pulmonary fibrosis: diagnosis and treatment in 2013].
AB  - Idiopathic pulmonary fibrosis (IPF), the etiopathogeny of which is still unknown,
      is the most frequent and severe of idiopathic interstitial pneumonias. It
      progressively leads, sometimes more acutely when exacerbations occur, to a
      restrictive respiratory insufficiency. Its prognosis is very dark with a median
      survival of 3-5 years. No treatment so far has been curative. Its diagnostic and
      therapeutic management has been greatly improved due to the technical progress in
      terms of high-resolution tomodensitometry, to the availability of new drugs with
      a real antifibrotic potential and to the production of international
      recommendations. The diagnosis is reached in 2/3 of IPF patients presenting with
      a typical usual interstitial pneumonitis (UIP) CT-scan pattern. It requires a
      videothoracoscopic biopsy in the remaining patients. Multidisciplinary
      discussions are key to a proper diagnosis of IPF. Pirfenidone is presently the
      only drug with a real antifibrotic potential in mild to moderate forms of the
      disease (FVC>50% and DLCO>35% predicted). The other ones have proved either
      inefficient or toxic. It is highly recommended to include patients in innovative
      targeted protocols. Non-pharmacological management of these patients comprises
      long-term oxygen therapy, pulmonary rehabilitation and overall lung
      transplantation. Pulmonary hypertension, to be detected regularly during the
      follow-up, is associated to a dark prognosis. No specific treatment is efficient
      in this context. Several comorbidities, particularly frequent in IPF, should be
      treated when present: gastro-oesophageal reflux, obstructive sleep apnea,
      emphysema. The particular high frequency of bronchopulmonary cancer should be
      highlighted. 

PMID- 24566025
TI  - [Therapeutic impact of molecular diagnosis in metastatic non-small cell lung
      cancer: targeted therapies in 2013].
AB  - Recent advances in the molecular characterization of metastatic unresectable lung
      cancers have markedly improved the management of patients. Today, molecular tests
      should be performed routinely in all patients with non-squamous non-small cell
      lung cancer, and in case of squamous cell carcinoma occurring in a non-smoker. In
      the presence of EGFR mutation or ALK rearrangement, specific inhibitors have
      shown superior efficacy to chemotherapy in first-line treatment for anti-EGFR
      (erlotinib and gefitinib) and in second-line treatment for anti-ALK (crizotinib).
      We will report the most recent clinical trials that aimed to identify effective
      therapeutic alternatives in case of acquired resistance to first-generation
      inhibitors (erlotinib, gefitnib, crizotinib), which inevitably occur in a median
      of 11-13 months at the first line setting and 7 months at the second line
      setting. Finally, we will describe more recently known molecular alterations such
      as ROS1 or RET rearrangements and HER2, BRAF, PIK3CA, DDR2 mutations. Some of
      these alterations are already elegible for dedicated targeted therapies within
      clinical trials or temporary use authorization (ATU). 

PMID- 24566026
TI  - [Diaphragmatic palsy and dysfunction: from physiology to surgery].
AB  - The clinical presentations of diaphragm dysfunctions vary according to etiologies
      and unilateral or bilateral diseases. Elevation of the hemidiaphragm from
      peripheral origins, the most frequent situation, requires a surgical treatment
      only in case of major functional impact. Complete morphological and functional
      analyses of the neuromuscular chain and respiratory tests allow the best
      selection of patients to be operated. The surgical procedure may be proposed only
      when the diaphragm dysfunction is permanent and irreversible. Diaphragm plication
      for eventration through a short lateral thoracotomy, or sometimes by
      videothoracoscopy, is the only procedure for retensioning the hemidiaphragm. This
      leads to a decompression of intrathoracic organs and a repositioning of abdominal
      organs without effect on the hemidiaphragm active contraction. Morbidity and
      mortality rates after diaphragm plication are very low, more due to the patient's
      general condition than to surgery itself. Functional improvements after
      retensioning for most patients with excellent long-term results validate this
      procedure for symptomatic patients. In case of bilateral diseases, very few
      bilateral diaphragm plications have been reported. Some patients with diaphragm
      paralyses from central origins become permanently dependent on mechanical
      ventilation whereas their lungs, muscles and nerves are intact. In patients
      selected by rigorous neuromuscular tests, a phrenic pacing may be proposed to
      wean them from respirator. Two main indications have been validated: high-level
      tetraplegia above C3 and congenital alveolar hypoventilation from central origin.
      After progressive reconditioning of the diaphragm muscles following phrenic
      pacing at thoracic level, more than 90% of patients can be weaned from respirator
      within a few weeks. This weaning improves the quality of life with more
      physiological breathing, restored olfaction, better sleep and better speech. The
      positive impact of diaphragm stimulation has also been evaluated in other
      degenerative neurological diseases, particularly the amyotrophic lateral
      sclerosis. For either central or peripheral diaphragm dysfunctions, a successful
      surgical treatment lies on a strict preoperative selection of patients.

PMID- 24566027
TI  - [Massive hemoptysis following thoracic aortic rupture: an advancing field].
AB  - We report the case of a 57-year-old woman who presented with massive hemoptysis
      and thoracic pain 3 years after the endovascular treatment of a thoracic aortic
      aneurysm. Emergency work up revealed the presence of an endoleak, leading to the
      pressurization of the aneurysm sac and its subsequent rupture into the lung
      parenchyma. The discussion includes presentation, clinical course, diagnosis,
      complications and new therapeutic options in the management of a massive
      hemoptysis secondary to aortic rupture. All together, the case and discussion
      highlight the classical rules of critical care and the recent advances in
      endovascular treatment of thoracic aortic rupture. 

PMID- 24566028
TI  - [Typical pulmonary carcinoid tumor: evolution, related prognostic factors and
      lymphadenectomy indications].
AB  - The bronchopulmonary typical carcinoid tumors are often considered as non
      metastatic neoplasia. The appearance of metastases is observed in 10% of the
      cases. We detail here studies based on the identification of the risk factors of
      metastases occurrence to adapt the lung surgery and lymph node dissection to the
      individual patient risk. 

PMID- 24566029
TI  - [Pediatric lung transplantation in Broussais-HEGP: a 23-year experience (1990
      2013)].
AB  - INTRODUCTION: Pediatric lung transplantations (LTx) remains a small part of LTx
      performed worldwide. The majority of these Tx concerns young adolescents,
      transplantations in infants being anecdotic. We conducted a retrospective study
      of LTx in children and adolescents in one center in Paris from the beginning of
      the 90's to 2013. METHODS: Data from Broussais then HEGP were collected
      retrospectively from 1990 to 2013: 380 LTx were reported in 368 patients
      including 111 LTx performed among children from 5 to 18 years of age (30%).
      RESULTS: One hundred and eleven patients received 121 LTx: 86 bilateral LTx, 13
      combined lung-liver, 3 monopulmonary, 5 heart-lung and 4 combined heart-lung
      liver Tx. Eighty-eight percent of the patients had cystic fibrosis. Median age
      was 14 years, weight 34 kg and height 144 cm. Median age of donors was 27 years,
      weight 60 kg and height 167 cm. Conditional survival for children was not
      different than adults: 72% at one year, 42% at 5 years, 37% at 10 years and 26%
      at 15 years. There was not overall early mortality after transplantation. Era
      graft survival was significantly higher after year 2000 (53% at 5 years vs 32%
      P=0.03). CONCLUSION: Lung transplantation among children under 18 years have
      similar outcome to those of adult patients.

PMID- 24566030
TI  - [Impact of induction therapies on pathology and outcome after surgical resection
      of non-small lung cancer: a 30-year experience of 859 patients].
AB  - The management of localized non-small cell lung cancer (NSCLC) has been modified
      over the last decades, with induction therapies being increasingly recommended as
      a prerequisite to surgical resection. However, the relative impact of chemo- and
      chemoradiotherapy on tumours' pathology and patients' survival is still
      discussed. METHODS: We set a retrospective study including every patient who
      underwent surgical resection for NSCLC in 2 French centres from 1980 to 2009. We
      then compared the tumours' pathology and patients' survival according to the use
      of induction chemotherapy (group 1) or induction chemoradiotherapy (group 2).
      RESULTS: There were 733 patients in group 1 and 126 patients in group 2. In group
      1, 669 patients (91%) had platinum-based chemotherapy, for 2 to 3 cycles in 564
      cases (77%). In group 2, chemoradiotheray was concomitant in 68 patients (54%),
      and sequential in 58 patients (46%). As compared with group 1, group 2 was
      characterized by younger age (mean 59.8+/-9.5 vs 56.4+/-9.6, respectively,
      P<.001), a higher rate of tumours deemed unresectable before induction treatment
      (25% vs 44%, P<.001), and a higher proportion of T4 (25% vs 44%, P<.001) or N2
      diseases (56% vs 69%, P=.005). The type of resection, postoperative
      complications, and postoperative mortality were not significantly different
      between groups. On final pathologic report, as compared with group 1, there were
      more N0 and N1 disease in group 2 (N0: 43% vs 58%, P=.002; N1: 22% vs 10%,
      P=.002) while the rate of N2 disease was comparable (34% vs 32%, P=ns). The
      median, 5-, and 10-year survivals were 28 months, 35%, and 21% for group 1, and
      29 months, 36%, and 23% for group 2, respectively (P=ns). CONCLUSION: As compared
      with induction chemotherapy, induction chemoradiotherapy was performed in more
      advanced NSCLC, and resulted in better downstaging, similar postoperative course,
      and comparable long-term outcome after surgical resection.

PMID- 24566031
TI  - [Lymphatic spread of lung cancer: anatomical lymph node chains unchained in
      zones].
AB  - Lung cancer is characterized by its lymphophilia. Its metastatic spread mainly
      occurs by tumor cells lymphatic drainage into the blood circulation. Initially,
      the lymph node TNM classification was based on clinical and therapeutic
      considerations, particularly concerning N2 involvement. The goals were to avoid
      futile exploratory thoracotomies without lung resection, to provide more accurate
      data from mediastinoscopy, and to take into account the radiation therapy fields.
      Since 1997, the international lymph node classification was more used to analyse
      the disparities within N1 and N2 groups. However, this attempt did not succeed in
      clarifying the lymphatic metastazing process, and was not progressing any more.
      Anatomy not being considered, it did not permit to grasp the anatomical and
      physiological significances of N2 and N3 involvement. In effect, this
      classification is now confined in zones and is lacking the anatomical and
      physiological descriptions that characterise the lymphatic pathways draining the
      lungs and their tumoral pathology. The stations proposed in numbers in
      cartographies should have gained in accuracy and in prognostic value if they had
      been expressed in their anatomical counterparts. 

PMID- 24566032
TI  - [New techniques in thoracic radiation therapy].
AB  - Advanced technologies have led to an improvement of target volume delineation and
      a higher accuracy in dose delivery. Stereotactic body radiotherapy, intensity
      modulated radiotherapy and respiratory gating allow new therapeutic perspectives
      along with an improvement of the therapeutic ratio. Ongoing trials aim to show
      the magnitude of gains in patient care with technical improvements. 

PMID- 24566033
TI  - [Lung cancer with heart failure--a cardiac and thoracic surgeon's collaboration].
AB  - Surgical resection is a validated therapeutic option for selected cases of
      pulmonary tumors invading the important mediastinal structures (caval vein,
      atrium, aorta or supra-aortic trunks). Here, we present a patient with a necrosed
      pulmonary tumor invading the left atrium, causing cardiac insufficiency. A
      complete surgical resection under extracorporeal circulation was performed by the
      thoracic and cardiac teams. Admitted in a bed-ridden state, the patient was
      discharged completely rehabilitated on postoperative day 13. He survived 1 year
      at home with a good quality of life. 

PMID- 24566034
TI  - [Venous thromboembolism and cancer].
AB  - Incidence of venous thromboembolism (VTE) is high in patients with cancer and
      varies with the type, the stage and the histologic type of the cancer but also
      with some anticancer therapies and patient related risk factors. Therapeutic
      trials on long-term prophylaxis have not provided convincing results. In patients
      with established VTE, the risk of recurrence and bleeding is high. Although
      prolonged treatment with low molecular weight heparin (LMWH) is more efficient
      than vitamin K antagonists in patients with VTE and cancer, it is already
      associated with a risk of recurrence which is much higher than in non-cancer
      patients. The nature of the treatment to be administered after the initial six
      months, which is often required in this context and the treatment of recurrent
      VTE during anticoagulant treatment are still debated. Some long-standing data
      suggest that LMWH could play an adjuvant role as specific anticancer treatment.
      These data have still not been confirmed in clinical trials but several studies
      in different cancer types are ongoing. 

PMID- 24566035
TI  - [Molecular profiling of non-small cell lung cancer].
AB  - The management of locally advanced and metastatic non-small cell lung cancer has
      been revolutionized thanks to recent progress in pathology and molecular biology.
      The first molecular subgroup is defined by activating mutations of the epidermal
      growth factor receptor (EGFR), and a dramatic response to specific tyrosine
      kinase inhibitors. Since then, multiple genetic alterations (KRAS, HER2, BRAF,
      PIK3CA, ALK, ROS, RET...) have been identified as potential target of novel
      therapies, and molecular profiling has become common practice. This review focus
      on the molecular alterations associated with non-small cell lung cancer,
      including molecular profiling and response to targeted therapies. 

PMID- 24566036
TI  - [Lymphatic extension and lymphangiogenesis in non-small cell lung cancer].
AB  - Lymph node metastasis is a major adverse prognostic factor of malignant tumors,
      including non-small cell lung carcinoma (NSCLC). However the characterization of
      tumor associated lymphatic vessels and lymphangiogenic mediators in NSCLC are
      recent and their prognostic role is debated. Lymphatic vascular invasion (LVI)
      appears like a robust adverse prognostic factor when reported in NSCLC. This
      parameter should be better standardized and could be of use in adjuvant therapy
      indications. Moreover, anti-lymphangiogenesis therapies are currently under
      investigation and may become part of the anti-cancer strategy. 

PMID- 24566037
TI  - A novel method of multi-parameter measurements for the mouse retina in vivo using
      optical coherence tomography.

PMID- 24566038
TI  - Pulmonary sustained release of insulin from microparticles composed of
      polyelectrolyte layer-by-layer assembly.
AB  - The present study tests the hypothesis that layer-by-layer (LbL) nanoassembly of
      thin polyelectrolyte films on insulin particles provides sustained release of the
      drug after pulmonary delivery. LbL insulin microparticles were formulated using
      cationic and anionic polyelectrolytes. The microparticles were characterized for
      particle size, particle morphology, zeta potential and in vitro release. The
      pharmacokinetics and pharmacodynamics of drug were assessed by measuring serum
      insulin and glucose levels after intrapulmonary administration in rats.
      Bronchoalveolar lavage (BAL) and evans blue (EB) extravasation studies were
      performed to investigate the cellular or biochemical changes in the lungs caused
      by formulation administration. The mass median aerodynamic diameter (MMAD) of the
      insulin microparticles was 2.7 MUm. Confocal image of the formulation particles
      confirmed the polyelectrolyte deposition around the insulin particles. Zeta
      potential measurements showed that there was charge reversal after each layering.
      Pulmonary administered LbL insulin formulation resulted in sustained serum
      insulin levels and concomitant decrease in serum glucose levels. The BAL and EB
      extravasation studies showed that the LbL insulin formulation did not elicit
      significant increase in marker enzymes activities compared to control group.
      These results demonstrate that the sustained release of insulin could be achieved
      using LbL nanoassembly around the insulin particles.

PMID- 24566040
TI  - Consolidated conversion of protein waste into biofuels and ammonia using Bacillus
      subtilis.
AB  - The non-recyclable use of nitrogen fertilizers in microbial production of fuels
      and chemicals remains environmentally detrimental. Conversion of protein wastes
      into biofuels and ammonia by engineering nitrogen flux in Escherichia coli has
      been demonstrated as a method to reclaim reduced-nitrogen and curb its
      environmental deposition. However, protein biomass requires a proteolysis process
      before it can be taken up and converted by any microbe. Here, we metabolically
      engineered Bacillus subtilis to hydrolyze polypeptides through its secreted
      proteases and to convert amino acids into advanced biofuels and ammonia
      fertilizer. Redirection of B. subtilis metabolism for amino-acid conversion
      required inactivation of the branched-chain amino-acid (BCAA) global regulator
      CodY. Additionally, the lipoamide acyltransferase (bkdB) was deleted to prevent
      conversion of branched-chain 2-keto acids into their acyl-CoA derivatives. With
      these deletions and heterologous expression of a keto-acid decarboxylase and an
      alcohol dehydrogenase, the final strain produced biofuels and ammonia from an
      amino-acid media with 18.9% and 46.6% of the maximum theoretical yield. The
      process was also demonstrated on several waste proteins. The results demonstrate
      the feasibility of direct microbial conversion of polypeptides into sustainable
      products. 

PMID- 24566041
TI  - Development of Halomonas TD01 as a host for open production of chemicals.
AB  - Genetic engineering of Halomonas spp. was seldom reported due to the difficulty
      of genetic manipulation and lack of molecular biology tools. Halomonas TD01 can
      grow in a continuous and unsterile process without other microbial
      contaminations. It can be therefore exploited for economic production of
      chemicals. Here, Halomonas TD01 was metabolically engineered using the gene
      knockout procedure based on markerless gene replacement stimulated by double
      strand breaks in the chromosome. When gene encoding 2-methylcitrate synthase in
      Halomonas TD01 was deleted, the conversion efficiency of propionic acid to 3
      hydroxyvalerate (3HV) monomer fraction in random PHBV copolymers of 3
      hydroxybutyrate (3HB) and 3HV was increased from around 10% to almost 100%, as a
      result, cells were grown to accumulate 70% PHBV in dry weight (CDW) consisting of
      12mol% 3HV from 0.5g/L propionic acid in glucose mineral medium. Furthermore,
      successful deletions on three PHA depolymerases eliminate the possible influence
      of PHA depolymerases on PHA degradation in the complicated industrial
      fermentation process even though significant enhanced PHA content was not
      observed. In two 500L pilot-scale fermentor studies lasting 70h, the above
      engineered Halomonas TD01 grew to 112g/L CDW containing 70wt% P3HB, and to 80g/L
      CDW with 70wt% P(3HB-co-8mol% 3HV) in the presence of propionic acid. The cells
      grown in shake flasks even accumulated close to 92% PHB in CDW with a significant
      increase of glucose to PHB conversion efficiency from around 30% to 42% after 48h
      cultivation when pyridine nucleotide transhydrogenase was overexpressed.
      Halomonas TD01 was also engineered for producing a PHA regulatory protein PhaR
      which is a robust biosurfactant. 

PMID- 24566042
TI  - Electron dose dependence of signal-to-noise ratio, atom contrast and resolution
      in transmission electron microscope images.
AB  - In order to achieve the highest resolution in aberration-corrected (AC) high
      resolution transmission electron microscopy (HRTEM) images, high electron doses
      are required which only a few samples can withstand. In this paper we perform
      dose-dependent AC-HRTEM image calculations, and study the dependence of the
      signal-to-noise ratio, atom contrast and resolution on electron dose and
      sampling. We introduce dose-dependent contrast, which can be used to evaluate the
      visibility of objects under different dose conditions. Based on our calculations,
      we determine optimum samplings for high and low electron dose imaging conditions.

PMID- 24566039
TI  - Assessment of the exhalation kinetics of volatile cancer biomarkers based on
      their physicochemical properties.
AB  - The current review provides an assessment of the exhalation kinetics of volatile
      organic compounds (VOCs) that have been linked with cancer. Towards this end, we
      evaluate various physicochemical properties, such as 'breath:air' and 'blood:fat'
      partition coefficients, of 112 VOCs that have been suggested over the past decade
      as potential markers of cancer. With these data, we show that the cancer VOC
      concentrations in the blood and in the fat span over 12 and 8 orders of
      magnitude, respectively, in order to provide a specific counterpart concentration
      in the exhaled breath (e.g., 1 ppb). This finding suggests that these 112
      different compounds have different storage compartments in the body and that
      their exhalation kinetics depends on one or a combination of the following
      factors: (i) the VOC concentrations in different parts of the body; (ii) the VOC
      synthesis and metabolism rates; (iii) the partition coefficients between
      tissue(s), blood and air; and (iv) the VOCs' diffusion constants. Based on this
      analysis, we discuss how this knowledge allows modeling and simulating the
      behavior of a specific VOC under different sampling protocols (with and without
      exertion of effort). We end this review by a brief discussion on the potential
      role of these scenarios in screening and therapeutic monitoring of cancer. 

PMID- 24566043
TI  - Beyond the N400: complementary access to early neural correlates of novel
      metaphor comprehension using combined electrophysiological and haemodynamic
      measurements.
AB  - The simultaneous application of different neuroimaging methods combining high
      temporal and spatial resolution can uniquely contribute to current issues and
      open questions in the field of pragmatic language perception. In the present
      study, comprehension of novel metaphors was investigated using near-infrared
      spectroscopy (NIRS) combined with the simultaneous acquisition of
      electroencephalography (EEG)/event-related potentials (ERPs). For the first time,
      we investigated the effects of figurative language on early electrophysiological
      markers (P200, N400) and their functional relationship to cortical haemodynamic
      responses within the language network (Broca's area, Wernicke's area). To this
      end, 20 healthy subjects judged 120 sentences with respect to their
      meaningfulness, whereby phrases were either literal, metaphoric, or meaningless.
      Our results indicated a metaphor-specific P200 reduction and a linear increase of
      N400 amplitudes from literal over metaphoric to meaningless sentences. Moreover,
      there were metaphor related effects on haemodynamic responses accessed with NIRS,
      especially within the left lateral frontal cortex (Broca's area). Significant
      correlations between electrophysiological and haemodynamic responses indicated
      that P200 reductions during metaphor comprehension were associated with an
      increased recruitment of neural activity within left Wernicke's area, indicating
      a link between variations in neural activity and haemodynamic changes within
      Wernicke's area. This link may reflect processes related to interindividual
      differences regarding the ability to classify novel metaphors. The present study
      underlines the usefulness of simultaneous NIRS measurements in language paradigms
      - especially for investigating the functional significance of neurophysiological
      markers that have so far been rarely examined - as these measurements are easily
      and efficiently realizable and allow for a complementary examination of neural
      activity and associated metabolic changes in cortical areas. 

PMID- 24566044
TI  - Physiological alterations in Bradybaena similaris (Stylommatophora:
      Bradybaenidae) induced by the entomopathogenic nematode Heterorhabditis indica
      (Rhabditida: Heterorhabditidae) strain LPP1.
AB  - Heterorhabditis is a nematode found in the soil that is used as an important
      biological control agent against various organisms. However, few studies have
      been performed of its use against snails and the present study is the first to
      investigate the effect of experimental exposure of Bradybaena similaris to
      Heterorhabditis indica LPP1. Two groups of 16 snails were formed: the control
      group (not exposed) and the treatment, which was exposed for three weeks to
      infective juveniles (J3) of H. indica LPP1. The entire experiment was conducted
      in duplicate, using a total of 64 snails. After this period, the snails were
      dissected to collect the hemolymph to evaluate the possible physiological
      alterations, namely total proteins, uric acid and hemolymph urea, as well as the
      activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST)
      as a result of the infection. The terrariums were analyzed on alternate days
      throughout the experiment to count the dead snails. Intense proteolysis was
      observed in the infected snails. An increase in the level of uric acid and
      reduction of the hemolymph urea content indicated that the infection by H. indica
      results in the inversion of the excretion pattern of the host snail. Variations
      in the aminotransferase activities were also observed, with the infected group
      presenting significantly higher values (p<0.05) than the control group for both
      ALT and AST. The exposure to H. indica LPP1 caused 55% mortality, with the
      highest rate observed in the first week after exposure (30%). These results
      suggest that the use of H. indica LPP1 is a feasible alternative for the
      biological control of B. similaris. 

PMID- 24566045
TI  - Assessing and mapping spatial associations among oral cancer mortality rates,
      concentrations of heavy metals in soil, and land use types based on multiple
      scale data.
AB  - In this study, a deconvolution procedure was used to create a variogram of oral
      cancer (OC) rates. Based on the variogram, area-to-point (ATP) Poisson kriging
      and p-field simulation were used to downscale and simulate, respectively, the OC
      rate data for Taiwan from the district scale to a 1 km * 1 km grid scale. Local
      cluster analysis (LCA) of OC mortality rates was then performed to identify OC
      mortality rate hot spots based on the downscaled and the p-field-simulated OC
      mortality maps. The relationship between OC mortality and land use was studied by
      overlapping the maps of the downscaled OC mortality, the LCA results, and the
      land uses. One thousand simulations were performed to quantify local and spatial
      uncertainties in the LCA to identify OC mortality hot spots. The scatter plots
      and Spearman's rank correlation yielded the relationship between OC mortality and
      concentrations of the seven metals in the 1 km cell grid. The correlation
      analysis results for the 1 km scale revealed a weak correlation between OC
      mortality rate and concentrations of the seven studied heavy metals in soil.
      Accordingly, the heavy metal concentrations in soil are not major determinants of
      OC mortality rates at the 1 km scale at which soils were sampled. The LCA
      statistical results for local indicator of spatial association (LISA) revealed
      that the sites with high probability of high-high (high value surrounded by high
      values) OC mortality at the 1 km grid scale were clustered in southern, eastern,
      and mid-western Taiwan. The number of such sites was also significantly higher on
      agricultural land and in urban regions than on land with other uses. The proposed
      approach can be used to downscale and evaluate uncertainty in mortality data from
      a coarse scale to a fine scale at which useful additional information can be
      obtained for assessing and managing land use and risk. 

PMID- 24566046
TI  - Climate-related hazards: a method for global assessment of urban and rural
      population exposure to cyclones, droughts, and floods.
AB  - Global climate change (GCC) has led to increased focus on the occurrence of, and
      preparation for, climate-related extremes and hazards. Population exposure, the
      relative likelihood that a person in a given location was exposed to a given
      hazard event(s) in a given period of time, was the outcome for this analysis. Our
      objectives were to develop a method for estimating the population exposure at the
      country level to the climate-related hazards cyclone, drought, and flood; develop
      a method that readily allows the addition of better datasets to an automated
      model; differentiate population exposure of urban and rural populations; and
      calculate and present the results of exposure scores and ranking of countries
      based on the country-wide, urban, and rural population exposures to cyclone,
      drought, and flood. Gridded global datasets on cyclone, drought and flood
      occurrence as well as population density were combined and analysis was carried
      out using ArcGIS. Results presented include global maps of ranked country-level
      population exposure to cyclone, drought, flood and multiple hazards. Analyses by
      geography and human development index (HDI) are also included. The results and
      analyses of this exposure assessment have implications for country-level
      adaptation. It can also be used to help prioritize aid decisions and allocation
      of adaptation resources between countries and within a country. This model is
      designed to allow flexibility in applying cyclone, drought and flood exposure to
      a range of outcomes and adaptation measures. 

PMID- 24566047
TI  - Risk factors of CVD mortality among the elderly in Beijing, 1992 - 2009: an 18
      year cohort study.
AB  - Few researchers have examined the effects of multiple risk factors of
      cardiovascular disease (CVD) mortality simultaneously. This study was to
      determine the associations of combined lifestyle and other factors with CVD
      mortality among the elderly (n = 3,257), in Beijing, China, through data mining
      of the Beijing Longitudinal Study of Aging (BLSA). BLSA is a representative
      cohort study from 1992 to 2009, hosted by Xuan Wu Hospital. Competing risk
      survival analysis was conducted to explore the association between risk factors
      and CVD mortality. The factors focused mainly on lifestyle, physical condition,
      and the model was adjusted for age and gender. There were 273 of the 1,068
      recorded deaths caused by CVD among the 2010 participants. Living in a suburban
      area (HR = 0.614, 95% CI: 0.410-0.921) was associated with lower CVD mortality.
      Increasing age (66-75: HR = 1.511, 95% CI: 1.111-2.055; >= 76: HR = 1.847, 95%
      CI: 1.256-2.717), high blood pressure (HR = 1.407, 95% CI: 1.031-1.920), frequent
      consumption of meat (HR = 1.559, 95% CI: 1.079-2.254) and physical inactivity (p
      = 0.046) were associated with higher CVD mortality. The study provides an
      instructional foundation for the control and prevention of CVD in Beijing, China.

PMID- 24566048
TI  - Recent evidence regarding triclosan and cancer risk.
AB  - Triclosan is a broad-spectrum antibacterial commonly used in cosmetics,
      dentifrices, and other consumer products. The compound's widespread use in
      consumer products and its detection in breast milk, urine, and serum have raised
      concerns regarding its potential association with various human health outcomes.
      Recent evidence suggests that triclosan may play a role in cancer development,
      perhaps through its estrogenicity or ability to inhibit fatty acid synthesis. Our
      aims here are to review studies of human exposure levels, to evaluate the results
      of studies examining the effects of triclosan on cancer development, and to
      suggest possible directions for future research.

PMID- 24566049
TI  - Indicators for tracking European vulnerabilities to the risks of infectious
      disease transmission due to climate change.
AB  - A wide range of infectious diseases may change their geographic range,
      seasonality and incidence due to climate change, but there is limited research
      exploring health vulnerabilities to climate change. In order to address this gap,
      pan-European vulnerability indices were developed for 2035 and 2055, based upon
      the definition vulnerability = impact/adaptive capacity. Future impacts were
      projected based upon changes in temperature and precipitation patterns, whilst
      adaptive capacity was developed from the results of a previous pan-European
      study. The results were plotted via ArcGISTM to EU regional (NUTS2) levels for
      2035 and 2055 and ranked according to quintiles. The models demonstrate regional
      variations with respect to projected climate-related infectious disease
      challenges that they will face, and with respect to projected vulnerabilities
      after accounting for regional adaptive capacities. Regions with higher adaptive
      capacities, such as in Scandinavia and central Europe, will likely be better able
      to offset any climate change impacts and are thus generally less vulnerable than
      areas with lower adaptive capacities. The indices developed here provide public
      health planners with information to guide prioritisation of activities aimed at
      strengthening regional preparedness for the health impacts of climate change.
      There are, however, many limitations and uncertainties when modeling health
      vulnerabilities. To further advance the field, the importance of variables such
      as coping capacity and governance should be better accounted for, and there is
      the need to systematically collect and analyse the interlinkages between the
      numerous and ever-expanding environmental, socioeconomic, demographic and
      epidemiologic datasets so as to promote the public health capacity to detect,
      forecast, and prepare for the health threats due to climate change. 

PMID- 24566050
TI  - Pupillometry in Chinese female patients with depression: a pilot study.
AB  - The pupillary responses to light in patients with depression and normal controls
      were evaluated among Chinese females. Four parameters related to the pupil were
      assessed using a video-based pupillometer. The results showed that there were
      significant differences in the pupil area in the darkness and the pupil area at
      the peak of constriction between depressed patients and normal controls. 

PMID- 24566052
TI  - Evaluation of health care system reform in Hubei Province, China.
AB  - This study established a set of indicators for and evaluated the effects of
      health care system reform in Hubei Province (China) from 2009 to 2011 with the
      purpose of providing guidance to policy-makers regarding health care system
      reform. The resulting indicators are based on the "Result Chain" logic model and
      include the following four domains: Inputs and Processes, Outputs, Outcomes and
      Impact. Health care system reform was evaluated using the weighted TOPSIS and
      weighted Rank Sum Ratio methods. Ultimately, the study established a set of
      indicators including four grade-1 indicators, 16 grade-2 indicators and 76 grade
      3 indicators. The effects of the reforms increased year by year from 2009 to 2011
      in Hubei Province. The health status of urban and rural populations and the
      accessibility, equity and quality of health services in Hubei Province were
      improved after the reforms. This sub-national case can be considered an example
      of a useful approach to the evaluation of the effects of health care system
      reform, one that could potentially be applied in other provinces or nationally. 

PMID- 24566051
TI  - Exploring powered wheelchair users and their caregivers' perspectives on
      potential intelligent power wheelchair use: a qualitative study.
AB  - Power wheelchairs (PWCs) can have a positive impact on user well-being, self
      esteem, pain, activity and participation. Newly developed intelligent power
      wheelchairs (IPWs), allowing autonomous or collaboratively-controlled navigation,
      could enhance mobility of individuals not able to use, or having difficulty
      using, standard PWCs. The objective of this study was to explore the perspectives
      of PWC users (PWUs) and their caregivers regarding if and how IPWs could impact
      on current challenges faced by PWUs, as well as inform current development of
      IPWs. A qualitative exploratory study using individual interviews was conducted
      with PWUs (n = 12) and caregivers (n = 4). A semi-structured interview guide and
      video were used to facilitate informed discussion regarding IPWs. Thematic
      analysis revealed three main themes: (1) "challenging situations that may be
      overcome by an IPW" described how the IPW features of obstacle avoidance, path
      following, and target following could alleviate PWUs' identified mobility
      difficulties; (2) "cautious optimism concerning IPW use revealed participants"
      addresses concerns regarding using an IPW as well as technological suggestions;
      (3) "defining the potential IPW user" revealed characteristics of PWUs that would
      benefit from IPW use. Findings indicate how IPW use may help overcome PWC
      difficulties and confirm the importance of user input in the ongoing development
      of IPWs. 

PMID- 24566053
TI  - Monitoring the transmission of Schistosoma japonicum in potential risk regions of
      China, 2008 - 2012.
AB  - Schistosomiasis japonica, caused by Schistosoma japonicum infection, remains a
      major public health concern in China, and the geographical distribution of this
      neglected tropical disease is limited to regions where Oncomelania hupensis, the
      intermediate host of the causative parasite, is detected. The purpose of this
      study was to monitor the transmission of S. japonicum in potential risk regions
      of China during the period from 2008 through 2012. To monitor the transmission,
      10 fixed surveillance sites and 30 mobile sentinel sites were selected in 10
      counties of four provinces, namely Anhui, Jiangsu, Chongqing and Hubei. There
      were 8, 9, 6, 2 and 3 cases infected with S. japonicum detected in the 30 mobile
      sentinel sites during the 5-year study period, while 27 subjects were positive
      for the antibody-based serum test in the 10 fixed sentinel sites; however, no
      infection was found. In addition, neither local nor imported livestock were found
      to be infected. No O. hupensis snails were detected in either the fixed
      surveillance or the mobile sentinel sites; however, the snail host was found to
      survive and reproduce at Chaohu Lake, inferring the potential of transmission of
      the disease. It is suggested that the continuous surveillance of schistosomiasis
      japonica should be carried out in both the endemic foci and potential risk
      regions of China, and an active, sensitive system to respond the potential risk
      of transmission seems justified. 

PMID- 24566054
TI  - Assessment of unsuspected exposure to drugs of abuse in children from a
      Mediterranean city by hair testing.
AB  - Hair testing was used to investigate the prevalence of unsuspected exposure to
      drugs of abuse in a group of children presenting to an urban paediatric emergency
      department without suggestive signs or symptoms. Hair samples were obtained from
      114 children between 24 months and 10 years of age attending the emergency room
      of Hospital del Mar in Barcelona, Spain. Hair samples from the accompanying
      parent were also collected. The samples were analyzed for the presence of
      opiates, cocaine, amphetamines, and cannabinoids by ultra-performance liquid
      chromatography-tandem mass spectrometry. Parental sociodemographics and possible
      drug of abuse history were recorded. Hair samples from twenty-three children
      (20.1%) were positive for cocaine (concentration range 0.15-3.81 ng/mg hair),
      those of thirteen children (11.4%) to cannabinoids (D9-THC concentration range
      0.05-0.54 ng/mg hair), with four samples positive to codeine (0.1-0.25 ng/mg
      hair), one positive for 2.09 ng methadone per mg hair and one to 6-MAM (0.42
      ng/mg hair) and morphine (0. 15 ng/mg hair) . In 69.5 and 69.2% of the positive
      cocaine and cannabinoids cases respectively, drugs was also found in the hair of
      accompanying parent. Parental sociodemographics were not associated with children
      exposure to drugs of abuse. However, the behavioural patterns with potential
      harmful effects for the child's health (e.g., tobacco smoking, cannabis,
      benzodiazepines and/or antidepressants use) were significantly higher in the
      parents of exposed children. In the light of the obtained results (28% overall
      children exposure to drugs of abuse) and in agreement with 2009 unsuspected 23%
      cocaine exposure in pre-school children from the same hospital, we support
      general hair screening to disclose exposure to drugs of abuse in children from
      risky environments to provide the basis for specific social and health
      interventions. 

PMID- 24566056
TI  - The relation between scores on noise annoyance and noise disturbed sleep in a
      public health survey.
AB  - The relation between responses to survey questions on noise annoyance and self
      reported sleep disturbance has been analysed to gain insight in its dependency on
      noise source or noise type and on individual characteristics. The results show a
      high correlation between responses (scores 0-10) with Pearson's correlation
      coefficient close to 0.8 for respondents who report hearing the source. At the
      same level of annoyance, scooters and neighbours are associated with more sleep
      disturbance, air and road traffic with less. The relation between Annoyance (A)
      and Sleep Disturbance (SD) is also significantly related to age, the use of
      sleeping drugs, and living alone. However, the differences in the A-SD relations
      with respect to source and characteristic are small. Noise-related sleep
      disturbance is associated more strongly to noise annoyance than it is to noise
      exposure. For transportation noise both scores are more often equal when the
      annoyance score is 7 or higher; this change in scoring behaviour could be an
      indication for a change to severe annoyance. 

PMID- 24566055
TI  - Environmental arsenic exposure and microbiota in induced sputum.
AB  - Arsenic exposure from drinking water is associated with adverse respiratory
      outcomes, but it is unknown whether arsenic affects pulmonary microbiota. This
      exploratory study assessed the effect of exposure to arsenic in drinking water on
      bacterial diversity in the respiratory tract of non-smokers. Induced sputum was
      collected from 10 subjects with moderate mean household water arsenic
      concentration (21.1 +/- 6.4 ppb) and 10 subjects with low household water arsenic
      (2.4 +/- 0.8 ppb). To assess microbiota in sputum, the V6 hypervariable region
      amplicons of bacterial 16s rRNA genes were sequenced using the Ion Torrent
      Personal Genome Machine. Microbial community differences between arsenic exposure
      groups were evaluated using QIIME and Metastats. A total of 3,920,441 sequence
      reads, ranging from 37,935 to 508,787 per sample for 316 chips after QIIME
      quality filtering, were taxonomically classified into 142 individual genera and
      five phyla. Firmicutes (22%), Proteobacteria (17%) and Bacteriodetes (12%) were
      the main phyla in all samples, with Neisseriaceae (15%), Prevotellaceae (12%) and
      Veillonellacea (7%) being most common at the genus level. Some genera, including
      Gemella, Lactobacillales, Streptococcus, Neisseria and Pasteurellaceae were
      elevated in the moderate arsenic exposure group, while Rothia, Prevotella,
      Prevotellaceae Fusobacterium and Neisseriaceae were decreased, although none of
      these differences was statistically significant. Future studies with more
      participants and a greater range of arsenic exposure are needed to further
      elucidate the effects of drinking water arsenic consumption on respiratory
      microbiota. 

PMID- 24566057
TI  - Potential for improved glycemic control with dietary Momordica charantia in
      patients with insulin resistance and pre-diabetes.
AB  - Bitter Melon (Momordica charantia) is a widely used traditional remedy for
      hyperglycemia. While the medicinal properties of this plant have been studied
      extensively using in vitro and animal models, the clinical efficacy and safety in
      humans is largely unknown. This review discusses the benefits and limitations of
      bitter melon supplementation in the context of epidemic levels of insulin
      resistance and pre-diabetes throughout the world. 

PMID- 24566058
TI  - Pre-hospital ECG E-transmission for patients with suspected myocardial infarction
      in the highlands of Scotland.
AB  - Patients with ST elevation myocardial infarction (STEMI) require prompt
      treatment, best done by primary percutaneous coronary intervention (PPCI).
      However, for patients unable to receive PPCI, immediate pre-hospital thrombolysis
      (PHT) is the best alternative. Evidence indicates that diagnostic and management
      support for staff increases the use of PHT. This study aimed to describe the
      patient demographics and management of patients, to determine any potential inter
      area differences in referral rates to the ECG e-transmission service and to
      explore the views and experiences of key staff involved in ECG e-transmission
      within NHS Highland. Data from 2,025 patient episodes of ECG e-transmission
      identified a statistically significant geographical variation in ECG e
      transmission and PHT delivery. Scottish Ambulance Service (SAS) staff were more
      likely than GPs to deliver PHT overall, however, GPs were more likely to deliver
      in remote areas. Interviews with six Cardiac Care Unit (CCU) nurses and six SAS
      staff highlighted their positive views of ECG e-transmission, citing perceived
      benefits to patients and interprofessional relationships. Poor access to network
      signal was noted to be a barrier to engaging in the system. This study has
      demonstrated that a specialist triage service based on e-transmission of ECGs in
      patients with suspected STEMI can be implemented in a diverse geographical
      setting. Work is needed to ensure equity of the service for all patients. 

PMID- 24566061
TI  - Attentional bias to activity of different parts of the body in children with
      functional abdominal pain: an experimental study.
AB  - OBJECTIVES: To investigate whether children with functional abdominal pain (FAP)
      show an attentional bias for their bodily activity, and whether receiving
      information about bodily activity influenced perception of bodily sensations.
      METHODS: A total of 30 children with FAP and 30 healthy children performed a dot
      probe task, in which they were shown sham pictures about their bodily activity.
      RESULTS: Contrary to our hypotheses, no attentional bias for gut activity was
      found in either group. However, children with FAP were slower than healthy
      children on all supraliminal gut-activity trials, suggesting that pictures of gut
      activity distracted children with FAP from the task they were performing. Both
      groups showed an attention bias away from supraliminal pictures about heart
      activity. As hypothesized, more children with FAP than healthy children reported
      increases in pain after the experiment. CONCLUSIONS: Children with FAP seemed
      more strongly influenced by information about gut activity than healthy children.
      The present study should be replicated for intervention purposes.

PMID- 24566060
TI  - Distribution of cells responsive to 5-HT6 receptor antagonist-induced hypophagia.
AB  - The central 5-hydroxytryptamine (5-HT; serotonin) system is well established as
      an important regulator of appetite and continues to remain a focus of obesity
      research. While much emphasis has focussed on the 5-HT(2C) receptor (5-HT(2C)R)
      in 5-HT's anorectic effect, pharmacological manipulation of the 5-HT6 receptor (5
      HT6R) also reduces appetite and body weight and may be amenable to obesity
      treatment. However, the neurological circuits that underlie 5-HT6R-induced
      hypophagia remain to be identified. Using c-fos immunoreactivity (FOS-IR) as a
      marker of neuronal activation, here we mapped the neuroanatomical targets
      activated by an anorectic dose of the 5-HT6R antagonist SB-399885 throughout the
      brain. Furthermore, we quantified SB-399855 activated cells within brain
      appetitive nuclei, the hypothalamus, dorsal raphe nucleus (DRN) and nucleus of
      the solitary tract (NTS). Our results reveal that 5-HT6R antagonist-induced
      hypophagia is associated with significantly increased neuronal activation in two
      nuclei with an established role in the central control of appetite, the
      paraventricular nucleus of the hypothalamus (PVH) and the NTS. In contrast, no
      changes in FOS-IR were observed between treatment groups within other
      hypothalamic nuclei or DRN. The data presented here provide a first insight into
      the neural circuitry underlying 5-HT6R antagonist-induced appetite suppression
      and highlight the PVH and NTS in the coordination of 5-HT6R hypophagia.

PMID- 24566059
TI  - Impulsive choice and anxiety-like behavior in adult rats exposed to chronic
      intermittent ethanol during adolescence and adulthood.
AB  - Binge drinking during adolescence and adulthood may have differential long-term
      effects on the brain. We investigated the long-term effects of chronic
      intermittent ethanol (CIE) exposure during adolescence and adulthood on
      impulsivity and anxiety-like behavior. Adolescent (adolescent-exposed) and adult
      (adult-exposed) rats were exposed to CIE/water on postnatal days (PND) 28-53 and
      PND146-171, respectively, and a 4-day ethanol/water binge on PND181-184 and
      PND271-274, respectively. During withdrawal from CIE and 4-day binge exposures,
      anxiety-like behavior and arousal were measured in the light-potentiated startle
      (LPS) and acoustic startle (ASR) procedures, respectively. Impulsive choice was
      evaluated in the delay discounting task (DDT) at baseline and after ethanol
      challenges. Independent of age, ASR and LPS were decreased during withdrawal from
      CIE exposure. In contrast, LPS was increased in adult-exposed, but not adolescent
      exposed, rats during withdrawal from the 4-day ethanol binge. CIE exposure had no
      effect on preference for the large delayed reward at baseline, independent of
      age. During DDT acquisition, CIE-exposed, compared with water-exposed rats,
      omitted more responses, independent of age, suggesting the CIE-induced disruption
      of cognitive processes. Ethanol challenges decreased preference for the large
      reward in younger adolescent-exposed rats but had no effect in older adult
      exposed rats, independent of previous CIE/water exposure. Taken together, the
      present studies demonstrate that CIE withdrawal-induced decreases in anxiety and
      arousal were not age-specific. CIE exposure had no long-term effects on baseline
      impulsive choice. Subsequent ethanol exposure produced age-dependent effects on
      impulsivity (increased impulsivity in younger adolescent-exposed rats) and
      anxiety-like behavior (increased anxiety-like behavior in older adult-exposed
      rats). 

PMID- 24566062
TI  - Where the PIP is the implant?
AB  - A 51-year-old woman, who had previous breast augmentation and a video-assisted
      thoracoscopic wedge resection of the lung, underwent breast implant replacement
      of Poly Implant Protheses (PIP) due to a loss of volume on the right side of the
      chest. During this procedure, no implant was found in the right subpectoral
      space; however, a large defect was observed in the fifth intercostal space. A
      computed tomography scan of the chest indicated a circular entity in the right
      pleural cavity, which was confirmed to be the lost implant during a subsequent
      video-assisted thoracoscopic surgery (VATS). 

PMID- 24566063
TI  - The role of proximal pulleys in preventing tendon bowstringing: pulley rupture
      and tendon bowstringing.
AB  - PURPOSE: The aim of this study was to investigate factors that contribute to
      tendon bowstringing at the proximal phalanx. We hypothesised that: (1) a partial
      rupture of the A2 pulley leads to significant bowstringing, (2) the location of
      the A2 rupture, starting proximally or distally, influences bowstringing, (3) an
      additional A3 pulley rupture causes a significant increase in bowstringing
      following a complete A2 pulley rupture and (4) the skin and tendon sheath may
      prevent bowstringing in A2 and A3 pulley ruptures. METHODS: Index, middle and
      ring fingers of eight freshly frozen cadaver arms were used. A loading device
      pulled with 100 N force was attached to the flexor digitorum profundus (FDP). The
      flexor digitorum superficialis (FDS) was preloaded with 5 N. Bowstringing was
      measured and quantified by the size of the area between the FDP tendon and the
      proximal phalanx over a distance of 5 mm with ultrasonography (US). RESULTS: US
      images showed that already a 30% excision of the A2 pulley resulted in
      significant bowstringing. In addition, a partial distal incision of the A2 pulley
      showed significantly more bowstringing compared to a partial proximal incision.
      Additional A3 pulley incision and excision of the proximal tendon sheath did not
      increase bowstringing. Subsequently, removing the skin did increase the
      bowstringing significantly. CONCLUSION: A partial A2 pulley rupture causes a
      significant bowstringing. A partial rupture of the A2 pulley at the distal rim of
      the A2 pulley resulted in more bowstringing than a partial rupture at the
      proximal rim.

PMID- 24566065
TI  - Nonsteroidal anti-inflammatory drugs and the heart.

PMID- 24566066
TI  - Duplex ultrasound in the diagnosis of lower-extremity deep venous thrombosis.

PMID- 24566067
TI  - ECG response: February 25, 2014.

PMID- 24566068
TI  - Neoatherosclerosis after paclitaxel-coated balloon angioplasty for in-stent
      restenosis.

PMID- 24566069
TI  - Fluttering thrombus in patent foramen ovale with paradoxical and cerebral
      embolism.

PMID- 24566071
TI  - Letter by Carnero-Alcazar et al regarding article, "Quantification of incomplete
      revascularization and its association with five-year mortality in the Synergy
      Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery
      (SYNTAX) Trial: validation of the residual SYNTAX Score".

PMID- 24566072
TI  - Response to letter regarding article, "Quantification of incomplete
      revascularization and its association with five-year mortality in the Synergy
      Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery
      (SYNTAX) Trial: validation of the residual SYNTAX Score".

PMID- 24566074
TI  - Evaluation of nociceptive Adelta- and C-fiber dysfunction with lidocaine using
      intraepidermal electrical stimulation.
AB  - OBJECTIVE: To investigate whether intraepidermal electrical stimulation (IES) can
      evaluate nociceptive Adelta- and C-fiber dysfunctions of an experimental model of
      small-fiber neuropathy (SFN) with transdermal lidocaine. METHODS: Lidocaine tape
      or placebo was applied to the dorsum of the feet in 14 healthy subjects. Reaction
      time (RT), sensory threshold, and evoked potentials (EPs) were measured using IES
      before, and 30 and 60 min after lidocaine/placebo application. RESULTS: All
      subjects felt pricking sensations following Adelta-fiber stimulation, and light
      painful sensations such as pricking, tingling, or burning following C-fiber
      stimulation using IES. RT was divided bimodally between Adelta- and C-fiber
      stimulations. At 30 min, lidocaine increased the sensory threshold and decreased
      the amplitude of EPs in both fiber stimulations. At 60 min, lidocaine's effects
      were greater for C fibers than for Adelta fibers. The sensory threshold and
      amplitude of EPs were unchanged among placebo sessions. CONCLUSIONS: IES
      demonstrated differential effects of transdermal lidocaine on nociceptive Adelta
      and C fibers, and elucidated the pathophysiology of the experimental model of
      SFN. SIGNIFICANCE: IES has advantages in terms of cost, convenience, and
      invasiveness. It may have potential for a clinical tool to elucidate the
      pathophysiology of patients with SFN, including the differences between Adelta
      and C fibers.

PMID- 24566075
TI  - Most people know little about the Affordable Care Act's provisions, US study
      finds.

PMID- 24566076
TI  - Post-Vietnam military herbicide exposures in UC-123 Agent Orange spray aircraft.
AB  - BACKGROUND: During the Vietnam War, approximately 20 million gallons of
      herbicides, including ~10.5 million gallons of dioxin-contaminated Agent Orange,
      were sprayed by about 34 UC-123 aircraft that were subsequently returned to the
      United States, without decontamination or testing, to three Air Force reserve
      units for transport operations (~1971-1982). In 1996, observed dioxin
      contamination led to withdrawal of these UC-123s from public auction and to their
      smelting in 2009. Current Air Force and Department of Veterans Affairs policies
      stipulate that "dried residues" of chemical herbicides and dioxin had not lead to
      meaningful exposures to flight crew and maintenance personnel, who are thus
      ineligible for Agent Orange-related benefits or medical examinations and
      treatment. Sparse monitoring data are available for analysis. METHODS: Three
      complementary approaches for modeling potential exposures to dioxin in the post
      Vietnam war aircraft were employed: (1) using 1994 and 2009 Air Force surface
      wipe data to model personnel exposures and to estimate dioxin body burden for
      dermal-oral exposure for dried residues using modified generic US Environmental
      Protection Agency intake algorithms; (2) comparing 1979 Air Force 2,4-
      dichlorophenoxyacetic acid and 2,4-5-trichlorophenoxyacetic acid air samples to
      saturated vapor pressure concentrations to estimate potential dioxin exposure
      through inhalation, ingestion and skin contact with contaminated air and dust;
      and (3) applying emission models for semivolatile organic compounds from
      contaminated surfaces to estimate airborne contamination. RESULTS: Model (1):
      Body-burden estimates for dermal-oral exposure were 0.92 and 5.4pg/kg body-weight
      day for flight crew and maintainers. The surface wipe concentrations were nearly
      two orders of magnitude greater than the US Army guidance level. Model (2):
      measured airborne concentrations were at least five times greater than saturated
      vapor pressure, yielding dioxin estimates that ranged from 13.2-27.0pg/m(3), thus
      supporting the likelihood of dioxin dust adsorption. Model (3): Theoretical
      models yielded consistent estimates to Model 2, 11-49pg/m(3), where the range
      reflects differences in experimental value of dioxin vapor pressure and surface
      area used. Model (3) results also support airborne contamination and dioxin dust
      adsorption. CONCLUSIONS: Inhalation, ingestion and skin absorption in aircrew and
      maintainers were likely to have occurred during post-Vietnam use of the aircraft
      based on the use of three complementary models. Measured and modeled values for
      dioxin exceeded several available guidelines. Deposition-aerosolization
      redeposition homeostasis of semivolatile organic compound contaminants,
      particularly dioxin, is likely to have continually existed within the aircraft.
      Current Air Force and Department of Veterans Affairs policies are not consistent
      with the available industrial hygiene measurements or with the widely accepted
      models for semivolatile organic compounds.

PMID- 24566077
TI  - [Pelvic reconstructions after bone tumor resection].
AB  - The three more frequent primitive malignant bone tumour which concerned the iliac
      bone are chondrosarcoma, following Ewing sarcoma and osteosarcoma. Wide resection
      remains the most important part of the treatment associated with chemotherapy for
      osteosarcoma and the Ewing sarcoma. Iliac wing resections and obdurate ring don't
      required reconstruction. However, acetabular resections and iliac wing resection
      with disruption of the pelvic ring required reconstruction to provide acceptable
      functional result. Acetabular reconstruction remains high technical demanding
      challenge. After isolated acetabular resection or associated to obdurate ring,
      our usual method of reconstruction is homolateral proximal femoral autograft and
      total hip prosthesis but it is possible to also used : saddle prosthesis, Mac
      Minn prosthesis with auto or allograft, modular prosthesis or custom made
      prosthesis, massive allograft with or without prosthesis and femoro-ilac
      arthrodesis. After resection of the iliac wing plus acetabulum, reconstruction
      can be performed by femoro-obturatrice and femora-sacral arthrodesis, homolateral
      proximal femoral autograft and prosthesis, femoral medialisation, massive
      allograft and massive allograft. Carcinological results are lesser than resection
      for distal limb tumor, local recurrence rate range 17 to 45%. Functional results
      after Iliac wing and obdurate ring are good. However, acetabular reconstruction
      provide uncertain functional results. The lesser results arrive after hemipelvic
      or acetabular and iliac wing resection-reconstruction, especially when gluteus
      muscles were also resected. The most favourable results arrive after isolated
      acetabular or acetabular plus obturateur ring resection-reconstruction.

PMID- 24566078
TI  - Revisiting the relationship between blood pressure and insulin-like growth factor
      1.
AB  - Conflicting evidence exists on the relationship between blood pressure (BP) and
      insulin-like growth factor-1 (IGF-1). We reviewed available articles and pooled
      extrapolated regression coefficients for the association between BP and total IGF
      1 as reported in the literature and included additional data from 912 individuals
      from the general population. We identified 20 studies including 11 704 subjects.
      We also measured total IGF-1, insulin-like binding protein-3, and BP in 912 black
      and white men and women from South Africa (aged 20-70 years). When plotting
      positive and negative weighed regression coefficients (29 data points) against
      IGF-1, we found a significant positive relationship (r=0.31; P<0.001; n=11 704)
      intercepting the 0 point at 191 ng/mL IGF-1, suggesting an inverse BP/IGF-1
      relationship in low IGF-1 conditions, and a positive relationship in overtly high
      IGF-1 conditions. In conclusion, our findings suggest that the relationship
      between BP and IGF-1 is dependent on, or related to, IGF-1 concentrations, as an
      expression of direct or reverse causality. Low IGF-1 bioavailability (associated
      with aging and vascular deterioration), resistance to IGF-1, and the complex
      interplay between IGF-1 and other vasoactive hormones could mask the
      vasoprotective functions of IGF-1 in cross-sectional studies or could modify
      their functions in prospective studies. 

PMID- 24566079
TI  - Should more significance be granted to medication response to antihypertensives
      in patients with resistant hypertension?

PMID- 24566080
TI  - Is hypertension associated with an accelerated aging of the brain?

PMID- 24566081
TI  - Endothelial cell mineralocorticoid receptors regulate deoxycorticosterone/salt
      mediated cardiac remodeling and vascular reactivity but not blood pressure.
AB  - Recent studies have identified novel pathological roles for mineralocorticoid
      receptors (MR) in specific cell types in cardiovascular disease. The mechanisms
      by which MR promotes inflammation and fibrosis involve multiple cell-specific
      events. To identify the role of MR in endothelial cells (EC-MR), the current
      study explored the vascular responses to aldosterone in wild-type (WT) and EC
      null mice (EC-MRKO). Nitric oxide function was impaired in the thoracic aorta and
      mesenteric arteries of aldosterone-treated WT mice. Although endothelial nitric
      oxide function was equivalently impaired in the mesenteric arteries of
      aldosterone-treated EC-MRKO mice, endothelial function was unaffected in the
      aorta, suggesting a differential role for EC-MR depending on the vascular bed.
      Second, the contribution of EC-MR to cardiovascular inflammation, fibrosis, and
      hypertension was determined in WT and EC-MRKO treated with
      deoxycorticosterone/salt for 8 days or 8 weeks. At 8 days, loss of EC-MR
      prevented macrophage infiltration and the expression of proinflammatory genes in
      the myocardium. Increased cardiac fibrosis was not detected in either genotype at
      this time, mRNA levels of profibrotic genes were significantly lower in EC-MRKO
      mice versus WT. At 8 weeks, deoxycorticosterone/salt treatment increased
      macrophage recruitment and proinflammatory gene expression in WT but not in EC
      MRKO. Collagen deposition and connective tissue growth factor expression were
      significantly reduced in EC-MRKO versus WT. Interestingly, systolic blood
      pressure was equivalently elevated in deoxycorticosterone/salt treated WT and EC
      MRKO. Our data demonstrate that (1) EC-MR signaling contributes to vascular
      nitric oxide function in large conduit arteries but not in resistance vessels and
      (2) an independent role for EC-MR in the inflammatory and profibrotic response to
      deoxycorticosterone/salt. 

PMID- 24566082
TI  - Implementation of rapid cortisol during adrenal vein sampling.

PMID- 24566083
TI  - Endothelial cell mineralocorticoid receptors: turning cardiovascular risk factors
      into cardiovascular dysfunction.

PMID- 24566084
TI  - Repeated-dose liver micronucleus assay of mitomycin C in young adult rats.
AB  - The repeated-dose liver micronucleus (RDLMN) assay has been previously reported
      to be effective for the detection of hepatocarcinogens and suitable for general
      toxicology studies. A collaborative study was conducted to evaluate whether this
      RDLMN assay using young adult rats without collagenase perfusion of the liver can
      be used to detect genotoxic carcinogens. In this study, we performed the RDLMN
      assay in young adult rats that received intraperitoneal injections of 0.25, 0.5
      or 1.0mg/kg/day of mitomycin C (MMC) for 14 and 28 days. The micronucleus
      induction in the bone marrow was concurrently measured, and a histopathological
      examination of the liver was conducted. The results revealed that the frequency
      of micronucleated hepatocytes (MNHEPs) was significantly increased in all of the
      treatment groups. However, the highest occurrence of MNHEPs was observed in the
      low-dose treatment group in both the 14- and the 28-day study periods. In
      addition, histopathological changes indicating hepatotoxicity were not observed
      even in the group that received the highest dose of MMC. There was no change in
      the frequency of metaphase hepatocytes in any of the treatment groups compared
      with our facility's background data. However, the frequency of proliferating
      hepatocytes, as assessed by Ki-67 positivity, was decreased at the highest dose,
      as was the frequency of MNHEPs. Therefore, the decreased induction of MNHEPs in
      the high-dose groups might be explained by suppression of hepatocyte cell
      division. In contrast, the frequency of micronucleated immature erythrocytes in
      the bone marrow significantly increased in a dose-dependent manner in all of the
      treatment groups in both study periods. Repeated treatment of MMC induced
      micronuclei in the liver. These results suggest that the novel RDLMN assay can be
      used to detect MMC genotoxicity in the liver. 

PMID- 24566085
TI  - Retinoic acid stabilizes antigen-specific regulatory T-cell function in
      autoimmune hepatitis type 2.
AB  - Imbalance between effector and regulatory T-cells (Treg) underlies the loss of
      immune-tolerance to self-antigens in autoimmune disease. In autoimmune hepatitis
      type 2 (AIH-2), effector CD4 T-cell immune responses to cytochrome P450IID6
      (CYP2D6) are permitted by numerically and functionally impaired Treg. Restoration
      of CYP2D6-specific Treg in AIH-2 would enable control over effectors sharing the
      same antigen specificity, leading to re-establishment of immune-tolerance. We
      have previously developed a protocol for generating antigen-specific Treg through
      co-culture with semi-mature dendritic cells presenting CYP2D6 peptides. In this
      study, we aimed to explore phenotypic and functional features of patient Treg
      compared to health, to test Treg stability under pro-inflammatory conditions, and
      to investigate the potential benefit of supplementation with all-trans-retinoic
      acid (RA) or rapamycin (RP), agents proven to enhance Treg function. We show that
      antigen-specific Treg from patients have comparable phenotypic and functional
      features to those from healthy controls, suppressing both proliferation and pro
      inflammatory cytokine production by effector cells. Treg exposure to inflammatory
      challenge results in decreased suppressive function and up-regulation of
      Th1/Th2/Th17 transcription factors both in health and AIH-2. The increase of Th1
      and Th17 transcription factors is limited by addition of RA in controls and Th1
      expression is decreased by RP in patients. Importantly, inflammation-induced
      decrease in Treg function is also abrogated by RA/RP in health and RA in
      patients. Our data provide important information for the optimization of
      protocols aiming at generating antigen-specific Treg for treatment of autoimmune
      disease and for understanding their biology upon pro-inflammatory challenge and
      RP/RA supplementation. 

PMID- 24566086
TI  - Analysis of covalent flavinylation using thermostable succinate dehydrogenase
      from Thermus thermophilus and Sulfolobus tokodaii lacking SdhE homologs.
AB  - Recent studies have indicated that post-translational flavinylation of succinate
      dehydrogenase subunit A (SdhA) in eukaryotes and bacteria require the chaperone
      like proteins Sdh5 and SdhE, respectively. How does covalent flavinylation occur
      in prokaryotes, which lack SdhE homologs? In this study, I showed that covalent
      flavinylation in two hyperthermophilic bacteria/archaea lacking SdhE, Thermus
      thermophilus and Sulfolobus tokodaii, requires heat and dicarboxylic acid. These
      thermophilic bacteria/archaea inhabit hot environments and are said to be
      genetically far removed from mesophilic bacteria which possess SdhE. Since
      mesophilic bacteria have been effective at covalent bonding in temperate
      environments, they may have caused the evolution of SdhE. 

PMID- 24566087
TI  - Sufficiently and insufficiently active lesbian, bisexual, and questioning female
      college students: sociodemographic factors among two age cohorts.
AB  - BACKGROUND: As rates of inactivity in the United States increase, the proportion
      of adults who are overweight in the United States continues to grow with
      concurrent increases in risk of weight-related morbidity and mortality. Sparse
      data are available on physical activity and weight in college-age sexual minority
      females, and none examine this relationship by age. To address this gap, we
      examined two age cohorts of female college students who self-identified as
      lesbian, bisexual, and questioning (LBQ), to 1) explore the relationship between
      physical activity, weight, and sociodemographic factors and 2) identify
      characteristics associated with sufficient physical activity in college females.
      METHODS: Data were from the 2010 American College Health Association National
      College Health Assessment survey. Descriptive statistics and chi-square tests
      were used to describe LBQ college women by age cohort (<=23 years, typical age
      vs. >=24 years, mature age) and physical activity level (sufficiently active vs.
      insufficiently active). Odds ratio and 95% confidence intervals from logistic
      regression were used to estimate the likelihood of meeting the physical activity
      guidelines. FINDINGS: Only one out of three LBQ college women report meeting the
      national physical activity guidelines. Characteristics of typical age and mature
      age LBQ college women varied by physical activity level. In a logistic regression
      model of LBQ college women, two characteristics increased the likelihood of being
      sufficiently activity: Reporting very good/excellent health and self-describing
      as "about the right weight." Three characteristics decreased the likelihood: Self
      describing as "very overweight," reporting action taken toward weight as "do
      nothing," and current smoking. CONCLUSIONS: With only one out of three LBQ
      college women meeting the national physical activity guidelines, interventions to
      increase physical activity, improve fitness, and potentially reduce unhealthy
      weight gain must start early to prevent the morbidity and mortality associated
      with inactivity.

PMID- 24566090
TI  - Central auditory function of deafness genes.
AB  - The highly variable benefit of hearing devices is a serious challenge in auditory
      rehabilitation. Various factors contribute to this phenomenon such as the
      diversity in ear defects, the different extent of auditory nerve hypoplasia, the
      age of intervention, and cognitive abilities. Recent analyses indicate that, in
      addition, central auditory functions of deafness genes have to be considered in
      this context. Since reduced neuronal activity acts as the common denominator in
      deafness, it is widely assumed that peripheral deafness influences development
      and function of the central auditory system in a stereotypical manner. However,
      functional characterization of transgenic mice with mutated deafness genes
      demonstrated gene-specific abnormalities in the central auditory system as well.
      A frequent function of deafness genes in the central auditory system is supported
      by a genome-wide expression study that revealed significant enrichment of these
      genes in the transcriptome of the auditory brainstem compared to the entire
      brain. Here, we will summarize current knowledge of the diverse central auditory
      functions of deafness genes. We furthermore propose the intimately interwoven
      gene regulatory networks governing development of the otic placode and the
      hindbrain as a mechanistic explanation for the widespread expression of these
      genes beyond the cochlea. We conclude that better knowledge of central auditory
      dysfunction caused by genetic alterations in deafness genes is required. In
      combination with improved genetic diagnostics becoming currently available
      through novel sequencing technologies, this information will likely contribute to
      better outcome prediction of hearing devices. 

PMID- 24566089
TI  - Structural determinants for the ouabain-stimulated increase in Na-K ATPase
      activity.
AB  - Recent studies suggest that at low concentrations, ouabain increases Na-K ATPase
      and NHE1 activity and activates the Src signaling cascade in proximal tubule
      cells. Our laboratory demonstrated that low concentrations of ouabain increase
      blood pressure in rats. We hypothesize that ouabain-induced increase in blood
      pressure and Na-K ATPase activity requires NHE1 activity and association. To test
      this hypothesis we treated rats with ouabain (1MUgkg body wt(-1)day(-1)) for
      9days in the presence or absence of the NHE1 inhibitor, zoniporide. Ouabain
      stimulated a significant increase in blood pressure which was prevented by
      zoniporide. Using NHE1-expressing Human Kidney cells 2 (HK2), 8 (HK8) and 11
      (HK11) and Mouse Kidney cells from Wild type (WT) and NHE1 knock-out mice (SWE)
      cell lines, we show that ouabain stimulated Na-K ATPase activity and surface
      expression in a Src-dependent manner in NHE1-expressing cells but not in NHE1
      deplete cells. Zoniporide prevented ouabain-induced stimulation of (86)Rb uptake
      in the NHE1-expressing cells. FRET and TIRF microscopy showed that ouabain
      increased association between GFP-NHE1 and mCherry-Na-K ATPase transfected into
      NHE1-deficient SWE cells. Mutational analysis demonstrated that the caveolin
      binding motif (CBM) of Na-K ATPase alpha1 is required for translocation of both
      Na-K ATPase alpha1 and NHE1 to the basolateral membrane. Mutations in activity or
      scaffold domains of NHE1 resulted in loss of ouabain-mediated regulation of Na-K
      ATPase. These results support that NHE1 is required for the ouabain-induced
      increase in blood pressure, and that the caveolin binding motif of Na-K ATPase
      alpha1 as well as the activity and scaffolding domains of NHE1 are required for
      their functional association. 

PMID- 24566088
TI  - Glucagon induces translocation of glucokinase from the cytoplasm to the nucleus
      of hepatocytes by transfer between 6-phosphofructo 2-kinase/fructose 2,6
      bisphosphatase-2 and the glucokinase regulatory protein.
AB  - Glucokinase activity is a major determinant of hepatic glucose metabolism and
      blood glucose homeostasis. Liver glucokinase activity is regulated acutely by
      adaptive translocation between the nucleus and the cytoplasm through binding and
      dissociation from its regulatory protein (GKRP) in the nucleus. Whilst the effect
      of glucose on this mechanism is well established, the role of hormones in
      regulating glucokinase location and its interaction with binding proteins remains
      unsettled. Here we show that treatment of rat hepatocytes with 25mM glucose
      caused decreased binding of glucokinase to GKRP, translocation from the nucleus
      and increased binding to 6-phosphofructo 2-kinase/fructose 2,6 bisphosphatase-2
      (PFK2/FBPase2) in the cytoplasm. Glucagon caused dissociation of glucokinase from
      PFK2/FBPase2, concomitant with phosphorylation of PFK2/FBPase2 on Ser-32, uptake
      of glucokinase into the nucleus and increased interaction with GKRP. Two novel
      glucagon receptor antagonists attenuated the action of glucagon. This establishes
      an unequivocal role for hormonal control of glucokinase translocation. Given that
      glucagon excess contributes to the pathogenesis of diabetes, glucagon may play a
      role in the defect in glucokinase translocation and activity evident in animal
      models and human diabetes. 

PMID- 24566091
TI  - Insertion site and sealing technique affect residual hearing and tissue formation
      after cochlear implantation.
AB  - Tissue formation around the electrode array of a cochlear implant has been
      suggested to influence preservation of residual hearing as well as electrical
      hearing performance of implanted subjects. Further, inhomogeneity in the
      electrical properties of the scala tympani shape the electrical field and affect
      current spread. Intracochlear trauma due to electrode insertion and the insertion
      site itself are commonly seen as triggers for the tissue formation. The present
      study investigates whether the insertion site, round window membrane (RWM) vs.
      cochleostomy (CS), or the sealing material, no seal vs. muscle graft vs.
      carboxylate cement, have an influence on the amount of fibrous tissue and/or new
      bone formation after CI implantation in the guinea pig. Hearing thresholds were
      determined by auditory brainstem response (ABR) measurements prior to
      implantation and after 28 days. The amount of tissue formation was quantified by
      evaluation of microscopic images obtained by a grinding/polishing procedure to
      keep the CI in place during histological processing. An insertion via the round
      window membrane resulted after 28 days in less tissue formation in the no seal
      and muscle seal condition compared to the cochleostomy approach. Between these
      two sealing techniques there was no difference. Sealing the cochlea with
      carboxylate cement resulted always in a strong new bone formation and almost
      total loss of residual hearing. The amount of tissue formation and the hearing
      loss correlated at 1-8 kHz. Consequently, the use of carboxylate cement as a
      sealing material in cochlear implantation should be avoided even in animal
      studies, whereas sealing the insertion site with a muscle graft did not induce an
      additional tissue growth compared to omitting a seal. For hearing preservation
      the round window approach should be used.

PMID- 24566092
TI  - Effects of diet-matrix on volatile organic compounds in breath in diet-induced
      obese mice.
AB  - Breath gas analysis in humans proved successful in identifying disease states and
      assessing metabolic functions in a non-invasive way. While many studies report
      diagnostic capability using volatile organic compounds (VOC) in breath, the inter
      individual variability even in healthy human cohorts is rather large and not
      completely understood in its biochemical origin. Laboratory mice are the
      predominant animal model system for human disorders and are analysed under highly
      standardized and controlled conditions. We established a novel setup to monitor
      VOCs as biomarkers for disease in the breath gas of non-anesthetized, non
      restrained mice using a proton transfer reaction mass spectrometer with time of
      flight detection. In this study, we implemented breath gas analysis in a dietary
      intervention study in C57BL/6J mice with the aim to assess the variability in VOC
      signatures due to a change in the diet matrix. Mice were fed a standard
      laboratory chow and then exposed to four semi-purified low- or high-fat diets for
      four weeks. Random forest (RF++) was used to identify VOCs that specifically
      respond to the diet matrix change. Interestingly, we found that the change from a
      chow diet to semi-purified diets resulted in a considerable drop of several VOC
      levels. Our results suggest that the diet matrix impacts VOC signatures and the
      underlying metabolic functions and may be one source of variability in exhaled
      volatiles. 

PMID- 24566093
TI  - Formulated extract from multiple citrus peels impairs dendritic cell functions
      and attenuates allergic contact hypersensitivity.
AB  - It has been reported that gold lotion (GL), a formulated product made from the
      peels of six citrus fruits, has many pharmacological properties, such as anti
      tumor, antioxidant, and anti-inflammatory activities. In this study, we
      investigated the immunomodulatory effect of GL on lipopolysaccharide (LPS)
      stimulated mouse bone marrow-derived DC maturation and function. Our experimental
      results have shown that GL significantly impaired the pro-inflammatory cytokine
      and chemokine secretion, suppressed the expression of major histocompatibility
      complex class I/II and costimulatory molecules (CD40, CD80 and CD86), increased
      phagocytic capacity, and reduced propensity to stimulate the autologous CD4(+)
      and CD8(+) T cell proliferation of LPS-induced DCs. Furthermore, we found that
      oral administration of GL attenuated the 2,4-Dinitro-1-fluorobenzene induced
      contact hypersensitivity (CHS) in animal models. Subsequently, our molecular
      mechanism studies showed that GL interfered with LPS-induced MAPK-JNK, p38
      phosphorylation and nuclear translocation of NF-kappaB p65. In an essence, these
      findings are the first report to provide new insight in the immunopharmacological
      role of GL in terms of its effects on DC. 

PMID- 24566094
TI  - HLA-B*35: 05 is a protective allele with a unique structure among HIV-1 CRF01_AE
      infected Thais, in whom the B*57 frequency is low.
AB  - OBJECTIVE: To identify protective human leukocyte antigen (HLA) alleles in an HIV
      infected south-east Asian population, in whom HLA-B*57 prevalence is lower than
      other ethnic groups, and HIV-1 CRF01_AE is the dominant circulating subtype.
      DESIGN: Cross-sectional study of Thai patients with chronic HIV infection.
      METHODS: Five hundred and fifty-seven HIV-1 CRF01_AE-infected Thais were
      recruited. Their HLA type and viral load were determined to statistically analyze
      the association of each allele in viral control. In-silico molecular dynamics was
      also used to evaluate the effect of HLA structure variants on epitope binding.
      RESULTS: HLA-B*35:05 was identified as the most protective allele (P=0.003,
      q=0.17), along with HLA-B*57:01 (P=0.044, q=0.31). Structurally, HLA-B*35:05
      belonged to the HLA-B*35-PY group of HLA-B*35 alleles; however, unlike the other
      HLA-B*35 alleles that carry Arg (R) at residue 97, it has unique sequences at
      T94, L95, and S97, located within the peptide-binding groove. Analysis of the
      three-dimensional HLA structure and molecular dynamics indicates that S97 in HLA
      B*35:05 leads to less flexibility in the groove, and shorter distances between
      the alpha-helixes compared with the disease-susceptible HLA-B*35-PY allele, HLA
      B*35:01. CONCLUSION: These data indicate the existence of a protective effect of
      HLA-B*57 across ethnic groups and highlight HLA-B*35:05 as an allele uniquely
      protective in subtype CRF01_AE-infected Thais. The divergence of HLA-B*35:05 from
      conventional HLA-B*35-PY structural sequences at the peptide-binding groove is
      consistent with previous studies that have identified HLA residue 97 as strongly
      influential in shaping HLA impact on immune control of HIV, and that a more
      restricted peptide-binding motif may be associated with improved control.

PMID- 24566095
TI  - Plasma plasminogen activator inhibitor-1 predicts myocardial infarction in HIV-1
      infected individuals.
AB  - OBJECTIVES: Biomarkers of endothelial dysfunction, inflammation and coagulation
      are associated with atherosclerosis and cardiovascular disease, but their
      association and possible predictive value remain controversial among HIV-1
      infected individuals. We sought to investigate the association of seven
      biomarkers with first-time myocardial infarction (MI) in an HIV-1-infected
      population. DESIGN: A matched case-control study of 54 cases and 54 controls.
      METHODS: We compared 54 HIV-1-infected patients with verified first-time MI and
      54 HIV-1-infected controls matched for age, duration of antiretroviral therapy,
      sex, smoking and no known cardiovascular disease. Levels of high-sensitivity C
      reactive protein, soluble endothelial selectin, soluble vascular cell adhesion
      molecule, soluble intercellular adhesion molecule, matrix metalloprotease 9,
      myeloperoxidase, and plasminogen activator inhibitor 1 (PAI-1) were measured
      using a Luminex assay in plasma samples from routine visits both 12 and 2 months
      prior to the case patient's MI. RESULTS: The two groups had similar HIV
      characteristics and traditional cardiovascular risk factors. In univariate
      analysis, PAI-1 levels were associated with MI, whereas none of the other markers
      showed any association.In multivariate analyses adjusting for the D:A:D risk
      score, HIV viral load and high-sensitivity C-reactive protein, PAI-1 levels in
      the highest quartile were associated with a six to seven-fold increased risk of
      MI in both samples. CONCLUSION: High levels of PAI-1 were associated with risk of
      first-time MI in HIV-1-infected individuals independently of cardiovascular risk
      factors, HIV parameters and antiretroviral therapy. Therefore PAI-1 may be used
      for risk stratification and prediction of CHD, but further studies are needed.

PMID- 24566097
TI  - Earlier initiation of ART and further decline in mother-to-child HIV transmission
      rates, 2000-2011.
AB  - OBJECTIVES: To analyze mother-to-child HIV transmission (MTCT) rates over time in
      light of changes in management, demographic, and pregnancy characteristics.
      DESIGN: Population-based surveillance data on diagnosed HIV-positive women and
      their infants are routinely collected in the UK and Ireland. METHODS: A total of
      12486 singleton pregnancies delivered in 2000-2011 were analyzed. HIV infection
      status was available for 11515 infants (92.2%). RESULTS: The rate of MTCT
      declined from 2.1% (17/816) in 2000-2001 to 0.46% (nine of 1975, 95% confidence
      interval: 0.21-0.86%) in 2010-2011 (trend, P=0.01), because of a combination of
      factors including earlier initiation of antenatal combination antiretroviral
      therapy (cART). Excluding 63 infants who were breastfed or acquired HIV
      postnatally, MTCT risk was significantly higher for all modes of delivery in
      women with viral load of 50-399  copies/ml (1.0%, 14/1349), compared with viral
      load of less than 50 copies/ml (0.09%, six of 6347, P<0.001). Among the former
      (viral load 50-399 copies/ml), the risk of MTCT was 0.26% (two of 777) following
      elective cesarean section and 1.1% (two of 188) following planned vaginal
      delivery (P=0.17), excluding in-utero transmissions. MTCT probability declined
      rapidly with each additional week of treatment initially, followed by a slower
      decline up to about 15 weeks of cART, with substantial differences by baseline
      viral load. CONCLUSION: MTCT rates in the UK and Ireland have continued to
      decline since 2006, reaching an all-time low of 5 per 1000 in 2010-2011. This was
      primarily because of a reduction in transmissions associated with late initiation
      or nonreceipt of antenatal cART, and an increase in the proportion of women on
      cART at conception.

PMID- 24566098
TI  - The effect of transient conditions on synovial fluid protein aggregation
      lubrication.
AB  - Little is known about the prevailing lubrication mechanisms in artificial
      articular joints and the way in which these mechanisms determine implant
      performance. The authors propose that interfacial film formation is determined by
      rheological changes local to the contact and is driven by aggregation of synovial
      fluid proteins within the contact inlet region. A direct relationship between
      contact film thickness and size of the protein aggregation within the inlet
      region has been observed. In this paper the latest experimental observations of
      the protein aggregation mechanism are presented for conditions which more closely
      mimic joint kinematics and loading. Lubricant films were measured for a series of
      bovine calf serum solutions for CoCrMo femoral component sliding against a glass
      disc. An optical interferometric apparatus was employed to study the effects of
      transient motion on lubricant film formation. Central film thickness was measured
      as a function of time for a series of transient entrainment conditions; start-up
      motion, steady-state and non-steady-state uni-directional sliding, and bi
      directional sliding. The size of the inlet aggregations was found to be dependent
      upon the type of transient condition. Thick protective protein films were
      observed to build up within the main contact region for all uni-directional
      tests. In contrast the inlet aggregation was not observed for bi-directional
      tests. Contact film thickness and wear was found to be directly proportional to
      the presence of the inlet protein phase. The inlet phase and contact films were
      found to be fragile when disrupted by surface scratches or subjected to reversal
      of the sliding direction. 

PMID- 24566099
TI  - Improving the diffusion of safety initiatives in community sport.
AB  - OBJECTIVES: The "Mayday Safety Procedure" (MSP) is included in the Australian
      Rugby Union (ARU) Medical and Safety Recommendations and the mandatory SmartRugby
      training for coaches. Previous research indicates that translating the Mayday
      Safety Procedure into practice among community rugby coaches is challenging. This
      study investigated whether Mayday Safety Procedure translation could be enhanced
      by systematically planning and implementing a range of theory-informed and
      context-specific diffusion strategies. DESIGN: A controlled before-and-after
      study. METHODS: Coaches of senior community rugby teams in five zones in New
      South Wales (Australia) were invited to complete a questionnaire about their
      Mayday Safety Procedure knowledge and practice at the end of the 2010 and 2011
      rugby seasons. During 2011, coaches in the intervention zone were exposed to a
      range of strategies to promote Mayday Safety Procedure diffusion which were
      planned by following Step 5 of the Intervention Mapping protocol. Coaches in the
      other four zones were exposed to usual strategies to promote Mayday Safety
      Procedure diffusion. RESULTS: Using the RE-AIM evaluation framework,
      statistically significant improvements were found among intervention zone coaches
      in: knowledge of most Mayday Safety Procedure key criteria; the number of coaches
      recognising their zone policy requiring them to train players in the Mayday
      Safety Procedure; frequency of provision of Mayday Safety Procedure training to
      players; coach perceptions of the quality of Mayday Safety Procedure training for
      players; and in confidence that referees could implement the Mayday Safety
      Procedure during a game if required. CONCLUSIONS: The findings suggest that the
      translation of injury prevention policy into community practice can be enhanced
      by developing and implementing a theory-informed, context-specific diffusion
      plan, undertaken in partnership with key stakeholders.

PMID- 24566100
TI  - Smoking cessation, maintenance, and relapse experiences among pregnant and
      postpartum adolescents: a qualitative analysis.
AB  - PURPOSE: To understand the experiences and processes of smoking cessation,
      maintenance, and relapse for pregnant and postpartum adolescents, whose
      perspectives and needs might be different from other age groups. METHODS: We
      conducted in-depth semistructured interviews with 52 pregnant and postpartum
      adolescents using tools of grounded theory analysis. RESULTS: Spontaneous smoking
      cessation during pregnancy was reported by most participants. This was generally
      explained as resulting from knowledge about the harmful effects of tobacco on the
      fetus, intense emotional reactions to this knowledge, or unpleasant tobacco- and
      pregnancy-related physical symptoms. Relapses were common, however. Most
      participants experienced guilt when they relapsed during pregnancy. Postpartum
      relapse was less fraught, as many participants no longer considered their smoking
      to negatively affect their infants. This was found even among adolescents who
      were breastfeeding. Participants who did maintain cessation postpartum typically
      reported support from smoke-free families and environments. CONCLUSIONS: The
      results of this study suggest a constellation of protective factors that
      contribute to smoking cessation and maintenance during and after pregnancy, as
      well as risk factors that contribute to temporary or permanent relapses. These
      results can inform future research and interventions on tobacco prevention among
      pregnant and postpartum adolescents. Several promising strategies for
      intervention development are discussed.

PMID- 24566096
TI  - Decline in locomotor functions over time in HIV-infected patients.
AB  - OBJECTIVES: To assess changes in locomotor function in HIV-infected patients and
      to evaluate the determinants of variations in lower limb muscle performance.
      DESIGN: Longitudinal study within the ANRS CO3 Aquitaine Cohort. METHODS:
      Standardized locomotor tests, including global functional capacity [6-min walk
      distance (6MWD)] and lower limb muscle performance tests [five times sit-to-stand
      (5STS) test], were performed in HIV-infected adults at baseline and 2-year follow
      up. Evolution of performances and determinants of 5STS time were studied in
      linear mixed-effects models. RESULTS: At baseline (354 patients, 90% on
      antiretroviral treatment), median 5STS time was 9.8 s and 6MWD 549 m. Poorer
      performances were associated with falls, reported by 12% of 178 patients at
      follow-up. Estimated mean deterioration was +0.24 s/year (P < 10) for 5STS time
      and -11 m/year (P < 10) for 6MWD. In multivariable analyses, older age was
      associated with worse baseline 5STS time (+0.47 s/10-year age increase; P = 10),
      but not with further deterioration. Deterioration was greater in prior injecting
      drug users compared to others (difference in slope +0.62 s/year; P = 0.04). 5STS
      time at any time point was worse in patients with history of cerebral AIDS
      conditions (+2.47 s; P < 10) and diabetes (+0.95 s; P = 0.02) than in others. No
      significant associations were found for antiretroviral treatment type, viral load
      or CD4 cell count. CONCLUSION: Compared to published data from healthy persons of
      similar age, baseline 5STS time and 6MWD were poorer in HIV-infected adults and
      associated with subsequent falls. Test performances deteriorated further over
      time. Age, diabetes, neurologic complications and injection drug use, rather than
      virologic factors, contribute to variations in lower limb muscle performance.

PMID- 24566101
TI  - Hepatitis C genotype 3: a tough match for interferon-free regimens.

PMID- 24566102
TI  - Deciphering the spectrum of low-grade hepatic encephalopathy in clinical
      practice.

PMID- 24566103
TI  - DCo(H2)ding the metabolic functions of SIRT1 in the intestine.

PMID- 24566104
TI  - What is the preferred approach to performing endoscopic retrograde
      cholangiopancreatography in patients with Roux-en-Y gastric bypass anatomy?

PMID- 24566105
TI  - The view of Barrett's esophagus from across the pond.

PMID- 24566106
TI  - Magic wand and crystal ball for primary sclerosing cholangitis.

PMID- 24566107
TI  - Potential role of the vitamin D receptor in control of cholesterol levels.

PMID- 24566108
TI  - IBD genetics: focus on (dys) regulation in immune cells and the epithelium.

PMID- 24566109
TI  - A vibrational spectroscopic study of the arsenate minerals cobaltkoritnigite and
      koritnigite.
AB  - Raman spectra of two well-defined types of cobaltkoritnigite and koritnigite
      crystals were recorded and interpreted. Significant differences in the Raman
      spectra of cobaltkoritnigite and koritnigite were observed. Observed Raman bands
      were attributed to the (AsO3OH)(2-) stretching and bending vibrations, stretching
      and bending vibrations of water molecules and hydroxyl ions. Both Raman and
      infrared spectra of cobaltkoritnigite identify bands which are attributable to
      phosphate and hydrogen phosphate anions proving some substitution of phosphate
      for arsenate in the structure of cobaltkoritnigite. The O-H?O hydrogen bond
      lengths in the crystal structure of koritnigite were inferred from the Raman
      spectra and compared with those derived from the X-ray single crystal refinement.
      The presence of (AsO3OH)(2-) units in the crystal structure of cobaltkoritnigite
      and koritnigite was proved from the Raman spectra which supports the conclusions
      of the X-ray structure analysis.

PMID- 24566111
TI  - Spectral and crystal studies on 5-(ethoxycarbonylmethoxy)-9
      (phenylazo)benzaldoxime: DFT approach.
AB  - 5-(Ethoxycarbonylmethoxy)-9-(phenylazo)benzaldoxime was synthesized from
      arylazosalicylaldehyde and characterized by IR, (1)H and (13)C NMR spectroscopy.
      The crystal structure of title compound was determined by X-ray crystallography.
      Single crystal data reveal trans configuration of aromatic rings about N=N bond
      and the two rings are nearly coplanar and oxime group adopts E configuration. The
      conformation of title compound was determined theoretically and N-O rotational
      barrier was also computed theoretically. HOMO-LUMO energies polarizability,
      hyperpolarizability, natural bond orbital (NBO), atom in molecule (AIM) analysis
      and atomic charges were also calculated theoretically according to density
      functional theory (DFT) method and analyzed.

PMID- 24566110
TI  - Crystal structure, DFT and HF calculations and radical scavenging activities of
      (E)-4,6-dibromo-3-methoxy-2-[(3-methoxyphenylimino)methyl]phenol.
AB  - In this study, (E)-4,6-dibromo-3-methoxy-2-[(3-methoxyphenylimino)methyl]phenol
      has been synthesized and characterized by using X-ray technique and FT-IR
      experimentally and using B3LYP/6-31G(d,p) and HF/6-31G(d,p) methods
      theoretically. The intermolecular and intramolecular interactions of the title
      compound have been determined according to X-ray results. The molecular geometry,
      vibrational frequencies of the title compound in the ground state have been
      calculated using the density functional B3LYP and HF method with the 6-31G(d,p)
      basis set and calculated bond parameters and vibrational frequencies values show
      good agreement with experimental values. Theoretical and experimental results
      show that tautomeric form of the structure is phenol-imine form. Besides HOMO
      LUMO energy gap, molecular electrostatic potential map were performed at B3LYP/6
      31G(d,p) level. It is worthy note of that, the free radical scavenging activities
      of the title compound were assessed using DPPH, DMPD(+), and ABTS(+) assays. The
      obtained results show that the title compound has effective DPPH (SC50 2.61+/
      0.09 MUg/mL), DMPD(+) (SC50 2.82+/-0.14 MUg/mL), and ABTS(+) (SC50 4.91+/-0.18
      MUg/mL) radical scavenging activities when compared with standard antioxidants
      (BHA, rutin, and trolox).

PMID- 24566112
TI  - Growth and characterization of an organic single crystal: 2-[2-(4-diethylamino
      phenyl)-vinyl]-1-methyl-pyridinium iodide.
AB  - Optically transparent crystal of the organic salt DEASI (2-[2-(4-Diethylamino
      phenyl)-vinyl]-1-methyl-pyridinium iodide) has been synthesized by using
      knoevenagel condensation reaction method. The synthesized material has been
      purified by successfully recrystallization process. Single crystals of DEASI have
      been grown by slow evaporation technique at room temperature. The solubility of
      the title material has been determined at different temperature in
      acetonitrile/methanol mixture. The cell parameters and crystallinity of the title
      crystal were determined by single crystal XRD. The powder diffraction was carried
      out to study the reflection plane of the grown crystal and diffraction peaks were
      indexed. The presence of different functional groups in the crystal was confirmed
      by Fourier transform infrared (FTIR) analysis. (1)H NMR spectrum was recorded to
      confirm the presence of hydrogen nuclei in the synthesized material. The optical
      property of the title crystal was studied by UV-Vis-NIR spectroscopic analysis.
      The melting point and thermal property of DEASI were studied using TGA/DSC
      technique. The Vicker's hardness (Hv) was carried out to know the category. The
      dielectric constant and dielectric loss of the compound decreases with an
      increase in frequencies. Chemical etching studies showed that the DEASI grows in
      the two dimensional growth mechanisms. The Kurtz-Perry powder second harmonic
      generation (SHG) test has done for title crystal. 

PMID- 24566113
TI  - Nano Mg(1-x)Ni(x)Al2O4 spinel pigments for advanced applications.
AB  - Nano Mg(1-x)Ni(x)Al2O4 spinel pigments were synthesized via polymeric combustion
      technique upon heat treatment at 210  degrees C. Citric acid in the presence of
      ethylene glycol polymer, with mass ratio of 60:40, was successfully used as a
      host network for the synthesis process. The obtained spinel was calcined at
      different temperatures; 300-1200 degrees C and investigated by thermal analysis
      (TG-DTG/DTA), X-ray powder diffraction (XRD), Fourier transform infrared
      spectroscopy (FT-IR), transmission electron microscopy (TEM), and scanning
      electron microscopy (SEM). UV-Vis and diffuse reflectance spectroscopy (DRS)
      using CIE-Lab/parameters methods have been used for color measurements. The
      addition of colored pigment on different types of glazes was studied. The results
      revealed that NiMgAl2O4 spinel beside MgNiO phases were crystallized with
      particle sizes of 9-21 nm at 600  degrees C and 52-180 nm at 1200  degrees C. All
      prepared samples exhibited green to pale green colors due to the inclusion of
      Ni(2+) inside the spinel structure. The pale green color intensity increased with
      increasing calcination temperature. The prepared pigment was suitable to convert
      commercial and opaque glazes to color product to be used in different
      applications.

PMID- 24566114
TI  - Immobilization of bacterial S-layer proteins from Caulobacter crescentus on iron
      oxide-based nanocomposite: synthesis and spectroscopic characterization of
      zincite-coated Fe2O3 nanoparticles.
AB  - Zinc oxide was coated on Fe2O3 nanoparticles using sol-gel spin-coating.
      Caulobacter crescentus have a crystalline surface layer (S-layer), which consist
      of one protein or glycoprotein species. The immobilization of bacterial S-layers
      obtained from C. crescentus on zincite-coated nanoparticles of iron oxide was
      investigated. The SDS PAGE results of S-layers isolated from C. crescentus showed
      the weight of 50 KDa. Nanoparticles of the Fe2O3 and zinc oxide were synthesized
      by a sol-gel technique. Fe2O3 nanoparticles with an average size of 50 nm were
      successfully prepared by the proper deposition of zinc oxide onto iron oxide
      nanoparticles surface annealed at 450  degrees C. The samples were characterized
      by field-emission scanning electron microscope (FESEM), atomic force microscopy
      (AFM), powder X-ray diffraction (XRD) and Fourier-transform infrared spectroscopy
      (FT-IR).

PMID- 24566115
TI  - Rapid identification of illegal synthetic adulterants in herbal anti-diabetic
      medicines using near infrared spectroscopy.
AB  - We created a rapid detection procedure for identifying herbal medicines illegally
      adulterated with synthetic drugs using near infrared spectroscopy. This procedure
      includes a reverse correlation coefficient method (RCCM) and comparison of
      characteristic peaks. Moreover, we made improvements to the RCCM based on new
      strategies for threshold settings. Any tested herbal medicine must meet two
      criteria to be identified with our procedure as adulterated. First, the
      correlation coefficient between the tested sample and the reference must be
      greater than the RCCM threshold. Next, the NIR spectrum of the tested sample must
      contain the same characteristic peaks as the reference. In this study, four pure
      synthetic anti-diabetic drugs (i.e., metformin, gliclazide, glibenclamide and
      glimepiride), 174 batches of laboratory samples and 127 batches of herbal anti
      diabetic medicines were used to construct and validate the procedure. The
      accuracy of this procedure was greater than 80%. Our data suggest that this
      protocol is a rapid screening tool to identify synthetic drug adulterants in
      herbal medicines on the market. 

PMID- 24566116
TI  - Ruthenium(II) bipyridine complexes bearing quinoline-azoimine (NN'N") tridentate
      ligands: synthesis, spectral characterization, electrochemical properties and
      single-crystal X-ray structure analysis.
AB  - Four octahedral ruthenium(II) azoimine-quinoline complexes having the general
      molecular formula [Ru(II)(L-Y)(bpy)Cl](PF6) {L-Y=YC6H4N=NC(COCH3)=NC9H6N, Y=H
      (1), CH3 (2), Br (3), NO2 (4) and bpy=2,2'-bipyrdine} were synthesized. The
      azoimine-quinoline based ligands behave as NN'N" tridentate donors and
      coordinated to ruthenium via azo-N', imine-N' and quinolone-N" nitrogen atoms.
      The composition of the complexes has been established by elemental analysis,
      spectral methods (FT-IR, electronic, (1)H NMR, UV/Vis and electrochemical (cyclic
      voltammetry) techniques. The crystal structure of complex 1 is reported. The
      Ru(II) oxidation state is greatly stabilized by the novel tridentate ligands,
      showing Ru(III/II) couples ranging from 0.93-1.27 V vs. Cp2Fe/Cp2Fe(+). The
      absorption spectrum of 1 in dichloromethane was modeled by time-dependent density
      functional theory (TD-DFT).

PMID- 24566117
TI  - Solvent influence on the excited states of the oxo form of barbituric acid and
      the mechanisms of the out-of-plane non-radiative elongation of the N-H bond: a
      comparative theoretical and experimental study.
AB  - The solvent influence on the excited states, emission and absorption energies of
      the oxo for of barbituric acid was studied with experimental (UV and fluorescence
      spectra) and theoretical methods. The excited-state reaction paths of the out-pf
      plane elongation of the N-H bond of the oxo form of barbituric acid were also
      investigated (TD DFT level) to the conical intersections mediating internal
      conversions to the ground state. The (1)nsigma* excited state was found to be the
      driven electronic state. We found that the increase of the polarity of the
      solvent reduces the (1)nsigma* excited state decay rate through a non-planar
      conical intersection and increases its energy. Thus, solvents with higher
      polarity disfavor the non-radiative decay through conical intersections.

PMID- 24566118
TI  - Investigation on the interaction of pyrene with bovine serum albumin using
      spectroscopic methods.
AB  - This paper was designed to investigate the interaction of pyrene with bovine
      serum albumin (BSA) under physiological condition by spectroscopic methods.
      Spectroscopic analysis of the emission quenching revealed that the quenching
      mechanism of BSA by pyrene was static. The binding sites and constants of pyrene
      BSA complex were observed to be 1.20 and 2.63*10(6) L mol(-1) at 298 K,
      respectively. The enthalpy change (DeltaH) and entropy change (DeltaS) revealed
      that van der Waals forces and hydrogen bonds stabilized the pyrene-BSA complex.
      Energy transfer from tryptophan to pyrene occurred by a FRET (fluorescence
      resonance energy transfer) mechanism, and the distance (r=2.72 nm) had been
      determined. The results of synchronous, three-dimensional fluorescence, and
      circular dichroism spectra showed that the pyrene induced conformational changes
      of BSA.

PMID- 24566119
TI  - Chemometric quality inspection control of pyrantel pamoate, febantel and
      praziquantel in veterinary tablets by mid infrared spectroscopy.
AB  - This paper describes the development and validation of a new multivariate
      calibration method based on diffuse reflectance mid infrared spectroscopy for
      direct and simultaneous determination of three veterinary pharmaceutical drugs,
      pyrantel pamoate, praziquantel and febantel, in commercial tablets. The best
      synergy interval partial least squares (siPLS) model was obtained by selecting
      three spectral regions, 3715-3150, 2865-2583, and 2298-1733 cm(-1), preprocessed
      by first derivative and Savitzky-Golay smoothing followed by mean centering. This
      model was built with five latent variables and provided root mean square errors
      of prediction (RMSEP) equal or lower than 0.69 mg per 100 mg of powder for the
      three analytes. The method was validated according the appropriate regulations
      through the estimate of figures of merit, such as trueness, precision, linearity,
      analytical sensitivity, bias and residual prediction deviation (RPD). Then, it
      was applied to three different veterinary pharmaceutical formulations found in
      the Brazilian market, in a situation of multi-product calibration, since the
      excipient composition of these commercial products, which was not known a priori,
      was modeled by an experimental design that scanned the likely content range of
      the possible constituents. The results were verified with high performance liquid
      chromatography with diode array detection (HPLC-DAD) and high performance liquid
      chromatography-tandem mass spectrometry (HPLC-MS/MS) and were in agreement with
      the predicted values at 95% confidence level. The developed method presented the
      advantages of being simple, rapid, solvent free, and about ten times faster than
      the HPLC ones.

PMID- 24566120
TI  - Exploring DNA binding and nucleolytic activity of few 4-aminoantipyrine based
      amino acid Schiff base complexes: a comparative approach.
AB  - A series of novel Co(II), Cu(II), Ni(II) and Zn(II) complexes were synthesized
      from Schiff base(s), obtained by the condensation of 4-aminoantipyrine with
      furfural and amino acid (glycine(L1)/alanine(L2)/valine(L3)) and respective
      metal(II) chloride. Their structural features and other properties were explored
      from the analytical and spectral methods. The binding behaviors of the complexes
      to calf thymus DNA were investigated by absorption spectra, viscosity
      measurements and cyclic voltammetry. The intrinsic binding constants for the
      above synthesized complexes are found to be in the order of 10(2) to 10(5)
      indicating that most of the synthesized complexes are good intercalators. The
      binding constant values (Kb) clearly indicate that valine Schiff-base complexes
      have more intercalating ability than alanine and glycine Schiff-base complexes.
      The results indicate that the complexes bind to DNA through intercalation and act
      as efficient cleaving agents. The in vitro antibacterial and antifungal assay
      indicates that these complexes are good antimicrobial agents against various
      pathogens. The IC50 values of [Ni(L1)2] and [Zn(L1)2] complexes imply that these
      complexes have preferable ability to scavenge hydroxyl radical. 

PMID- 24566121
TI  - Cutaneous mucormycosis in a patient with acute lymphocytic leukemia.

PMID- 24566122
TI  - Hypothalamus-pituitary axis: an obligatory target for endocannabinoids to inhibit
      steroidogenesis in frog testis.
AB  - Endocannabinoids - primarily anandamide (AEA) and 2-arachidonoylglycerol (2-AG) -
      are lipophilic molecules that bind to cannabinoid receptors (CB1 and CB2). They
      affect neuroendocrine activity inhibiting gonadotropin releasing hormone (GnRH)
      secretion and testosterone production in rodents, through a molecular mechanism
      supposed to be hypothalamus dependent. In order to investigate such a role, we
      choose the seasonal breeder, the anuran amphibian Rana esculenta, an experimental
      model in which components of the endocannabinoid system have been characterized.
      In February, at the onset of a new spermatogenetic wave, we carried out in vitro
      incubations of frog testis with AEA, at 10(-9)M dose. Such a treatment had no
      effect on the expression of cytochrome P450 17alpha hydroxylase/17,20 lyase
      (cyp17) nor 3-beta-hydroxysteroid dehydrogenase/Delta-5-4 isomerase (3beta-HSD),
      key enzymes of steroidogenesis. To understand whether or not the functionality of
      the hypothalamus-pituitary axis could be essential to support the role of
      endocannabinoids in steroidogenesis, frogs were injected with AEA, at 10(-8)M
      dose. Differently from in vitro experiment, the in vivo administration of AEA
      reduced the expression of cyp17 and 3beta-HSD. Whereas the effect on 3beta-HSD
      was counteracted by SR141716A (Rimonabant) - a selective antagonist of CB1, thus
      indicating a CB1 dependent modulation - the effect on cyp17 was not, suggesting a
      possible involvement of receptors other than CB1, probably the type-1 vanilloid
      receptor (TRPV1), since AEA works as an endocannabinoid and an endovanilloid as
      well. In conclusion our results indicate that endocannabinoids, via CB1, inhibit
      the expression of 3beta-HSD in frog testis travelling along the hypothalamus
      pituitary axis. 

PMID- 24566124
TI  - Are plants used for skin care in South Africa fully explored?
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: South Africa is an important focal point of
      botanical diversity, and although many plant species have been used since ancient
      times in ethnomedicine, only a few species have hitherto been fully investigated
      scientifically. A large proportion of the South African population use
      traditional medicines for their physical and psychological health needs. Many
      medicinal plants have recently gained popularity as ingredient in cosmetic
      formulations based on their ethnomedicinal values and many cosmetic products sold
      in stores are of natural origin. The present review discusses the
      ethnopharmacological values, pharmacological and toxicological evidence of 117
      plant species grown in South Africa, which are used traditionally for skin care
      purposes. Special focus was on their traditional use for many skin disorders in
      order to identify their therapeutic potential, the state of ethnopharmacological
      knowledge and special emphasis has been on areas which require further research.
      MATERIALS AND METHODS: The information regarding all 117 plant species mentioned
      was extracted from Sci-Finder, Science direct, Medline and Google Scholar. All
      the available relevant data for medicinal plants was collated from literature
      review articles from the 19th century to early 2013. RESULTS: The extracts from
      different parts of plants exhibited significant pharmacological properties,
      proving significant skin care potentials. Special emphasis was on those plant
      species which still need further exploration and these have been documented
      separately. CONCLUSIONS: Despite the immense use of plants in ethnomedicine for
      skin care, limited research has been done on the activity of the crude extracts
      and very little on the active constituents. Consequently, almost 35 out of the
      117 species are totally unexplored in the area of skin care. This investigation
      would be of interest to a broad readership including those researchers working in
      this field. The plant species namely: Greyia flanaganii, Sideroxylon inerme,
      Sclerocarya birrea, Calodendrum capense, Hyaenanche globosa, Harpephyllum
      caffrum, Ximenia americana, Leucosidea sericea Artemisia afra, and six Aloe
      species have been scientifically validated by our research group for skin
      hyperpigmentation problems.

PMID- 24566123
TI  - Intermittent cocaine self-administration produces sensitization of stimulant
      effects at the dopamine transporter.
AB  - Previous literature investigating neurobiological adaptations following cocaine
      self-administration has shown that high, continuous levels of cocaine intake
      (long access; LgA) results in reduced potency of cocaine at the dopamine
      transporter (DAT), whereas an intermittent pattern of cocaine administration
      (intermittent access; IntA) results in sensitization of cocaine potency at the
      DAT. Here, we aimed to determine whether these changes are specific to cocaine or
      translate to other psychostimulants. Psychostimulant potency was assessed by fast
      scan cyclic voltammetry in brain slices containing the nucleus accumbens
      following IntA, short access, and LgA cocaine self-administration, as well as in
      brain slices from naive animals. We assessed the potency of amphetamine (a
      releaser), and methylphenidate (a DAT blocker, MPH). MPH was selected because it
      is functionally similar to cocaine and structurally related to amphetamine. We
      found that MPH and amphetamine potencies were increased following IntA, whereas
      neither was changed following LgA or short access cocaine self-administration.
      Therefore, whereas LgA-induced tolerance at the DAT is specific to cocaine as
      shown in previous work, the sensitizing effects of IntA apply to cocaine, MPH,
      and amphetamine. This demonstrates that the pattern with which cocaine is
      administered is important in determining the neurochemical consequences of not
      only cocaine effects but potential cross-sensitization/cross-tolerance effects of
      other psychostimulants as well. 

PMID- 24566125
TI  - Proteomic analysis of the urine of Dirofilaria immitis infected dogs.
AB  - Canine cardiopulmonary dirofilariosis caused by Dirofilaria immitis habitually
      develops as a chronic disease affecting pulmonary arteries, lung parenchyma and
      heart. Other organs like kidneys can also be involved. Renal pathology is a
      consequence of glomerulonephritis whose main sign is proteinuria. The aim of the
      present work is to identify proteins excreted in the urine of D. immitis infected
      dogs showing proteinuria, and the possible contribution of their loss to
      heartworm disease. Proteinuria is higher in microfilaremic (mf+) than in
      amicrofilaremic (mf-) dogs. Using bidimensional electrophoresis and mass
      spectrometry 9 different proteins from Canis lupus familiaris in the urine of
      both mf- and mf+ dogs were identified (serotransferrin isoform 6, serum albumin
      precursor, albumin, immunoglobulin gamma heavy chain D, apolipoprotein A-I,
      immunoglobulin lambda-like polypeptide 5-like, arginine esterase precursor,
      inmunoglobulin gamma heavy chain B and hemoglobin subunit alpha). Furthermore, 3
      additional proteins were identified only in the urine of mf+ dogs, corresponding
      to dog fibrinogen alpha chain and immunoglobulin gamma heavy chain A and actin 2
      homologous to a protein of Brugia malayi. The loss of these proteins and other in
      the urine of D. immitis infected dogs could affect the general condition of
      parasitized dogs through the interference in the cholesterol metabolism and O2
      transport, among other mechanisms.

PMID- 24566126
TI  - Lungworms of the genus Troglostrongylus (Strongylida: Crenosomatidae): neglected
      parasites for domestic cats.
AB  - Feline lungworms belonging to the Troglostrongylus genus have been neglected for
      a long time. However, recent reports of Troglostrongylus brevior and
      Troglostrongylus subcrenatus in domestic cats have stimulated the interest of the
      scientific community on these lungworms. Troglostrongylus spp. have an indirect
      life cycle, which overlaps that of the better known Aelurostrongylus abstrusus.
      Nonetheless, adult worms of both genera have a distinct morphology and
      localization within the respiratory system of definitive hosts and, potentially,
      a different epidemiology and pathogenicity. As copromicroscopy has a low
      specificity for metastrongyloids due to the similarities of first-stage larvae,
      specific morphometrical keys and/or PCR diagnostic tools are advocated.
      Accordingly, more clinical studies and necropsy data are needed to elucidate the
      impact of Troglostrongylus spp. on the health of domestic cats. This article
      reviews current information on Troglostrongylus spp. as well as data on their
      occurrence in Europe and reports specific key morphological characters for the
      identification of adults and larvae, which is important to refine their diagnosis
      and for a better understanding of the feline lungworm infections. 

PMID- 24566127
TI  - Combination anthelmintics effectively control ML-resistant parasites; a real
      world case history.
AB  - Routine investigation into an ill-thrift situation with grazing cattle led to the
      discovery of the first reported case of macrocyclic lactone (ML) resistance in
      cattle in the USA. Research revealed that resistant parasites were originating on
      pastures in southeastern USA and were not an anomalous resident population on
      Wisconsin pastures. Prior to using anthelmintics in combination, ML-resistant
      Cooperia and Haemonchus spp. were shown to survive treatment with single-active
      MLs and were being transported in shipped cattle and seeding summer grazing
      pastures. Treatment and management strategies implemented in 2011 and 2012
      suggested that ML-surviving parasites were introduced into the conditioning
      facility and surviving treatment with ML. Data also demonstrated the use of
      combination ML+oral levamisole was highly effective in minimizing the transport
      of ML-surviving parasites from southeastern USA to Wisconsin pastures. The value
      of fecal egg count monitoring and PCR evaluation of nematode species under
      production conditions are confirmed. 

PMID- 24566128
TI  - Echinococcus canadensis (G7) and Echinococcus granulosus sensu stricto (G1) in
      swine of southern Brazil.
AB  - The cystic echinococcosis (CE) is an important zoonotic disease caused by the
      parasite Echinococcus spp. In Brazil, this parasite is present in Rio Grande do
      Sul (RS) state, border with Argentina and Uruguay, causing several damages to
      human and animal health. This study aimed to identify Echinococcus spp. in
      hydatid cysts of swine and evaluate the similarity of the genotypes through the
      phylogenetic analysis. A total of 3,101,992 swine were slaughtered in the
      central/northern region of RS/Brazil, during 2008-2012. Five isolates were
      characterized as hydatid cyst by molecular analysis, based on the mitochondrial
      gene cytochrome c oxidase subunit I (cox-I). The genotypes E. granulosus sensu
      stricto (G1) (n=2) and E. canadensis (G7) (n=3) were identified in the hydatid
      cysts. The swine represents a potential intermediate host for different genotypes
      of Echinococcus spp., besides it can contribute to the perpetuation of the
      parasite's life cycle in rural areas. 

PMID- 24566129
TI  - Evaluation of the compartment bag test for the detection of Escherichia coli in
      water.
AB  - AIMS: Annually, more than 2 million diarrheal disease deaths can be attributed to
      the lack of access to water, sanitation and hygiene. These deaths occur mostly in
      developing countries where water quality testing resources are limited. Several
      tests are currently used to detect and quantify Escherichia coli and other fecal
      bacteria in drinking water; however they can be expensive, complex, and
      technically demanding. There is a need for a simple, reliable, low-cost water
      quality test that can be used in resource limited settings. Therefore, the
      purpose of this research was to perform a rigorous evaluation of the recently
      developed compartment bag test for detection and quantification of E. coli
      against the standard method of membrane filtration. METHODS AND RESULTS: A total
      of 270 water samples were collected from forty-five various naturally
      contaminated water sources around metro-Atlanta from August 2011 through April
      2012. Samples were processed using the compartment bag test and membrane
      filtration with mI agar. Concentrations of E. coli were significantly correlated
      with a correlation coefficient of 0.904 (95% CI 0.859-0.950). Sensitivity and
      specificity were 94.9% and 96.6%, respectively. CONCLUSIONS: These results
      suggest that the compartment bag test produces results consistent with those
      produced by membrane filtration on mI agar. Based upon its performance, the
      compartment bag test has the potential to be used as a reliable, affordable
      drinking water quality test where other microbial water quality testing resources
      are not readily available.

PMID- 24566130
TI  - A new method for the preservation of axenic fungal cultures.
AB  - Microbiological work requires a reliable source of cultures that are not only
      well defined and taxonomically determined, but are also adequately preserved
      without changes in their morphological, physiological and genetic traits. Here we
      describe an easy, cost effective and rapid method for reliably preserving
      filamentous fungi on cellophane pieces at -80 degrees C for use in laboratory
      culture collections. 

PMID- 24566131
TI  - Low dose effects of ionizing radiation on normal tissue stem cells.
AB  - In recent years, there has been growing evidence for the involvement of stem
      cells in cancer initiation. As a result of their long life span, stem cells may
      have an increased propensity to accumulate genetic damage relative to
      differentiated cells. Therefore, stem cells of normal tissues may be important
      targets for radiation-induced carcinogenesis. Knowledge of the effects of
      ionizing radiation (IR) on normal stem cells and on the processes involved in
      carcinogenesis is very limited. The influence of high doses of IR (>5Gy) on
      proliferation, cell cycle and induction of senescence has been demonstrated in
      stem cells. There have been limited studies of the effects of moderate (0.5-5Gy)
      and low doses (<0.5Gy) of IR on stem cells however, the effect of low dose IR (LD
      IR) on normal stem cells as possible targets for radiation-induced carcinogenesis
      has not been studied in any depth. There may also be important parallels between
      stem cell responses and those of cancer stem cells, which may highlight potential
      key common mechanisms of their response and radiosensitivity. This review will
      provide an overview of the current knowledge of radiation-induced effects on
      normal stem cells, with particular focus on low and moderate doses of IR.

PMID- 24566132
TI  - UK paediatrician is criticised over handling of baby's death.

PMID- 24566133
TI  - Role of vesicular trafficking in skeletal dynamics.
AB  - Vesicular trafficking is critical for the function of bone cells, exemplified by
      bone diseases such as osteopetrosis, which frequently results from defects in
      this process. Recent work has further dissected the role of the endolysosomal
      system in both bone formation by osteoblasts and bone resorption by osteoclasts.
      This pathway also plays an important role in the communication between these and
      other cells in bone, through trafficking and degradation of growth factors and
      their receptors, and microvesicle release. In addition, a crucial role for
      autophagy in bone remodelling and bone disease is beginning to emerge. These
      insights into the molecular control of bone remodelling raise the possibility of
      developing novel therapeutics for bone diseases designed to target specific
      aspects of this process. 

PMID- 24566134
TI  - Residual gas analyzer mass spectrometry for human breath analysis: a new tool for
      the non-invasive diagnosis of Helicobacter pylori infection.
AB  - A residual gas analyzer (RGA) coupled with a high vacuum chamber is described for
      the non-invasive diagnosis of the Helicobacter pylori (H. pylori) infection
      through 13C-urea breath analysis. The present RGA-based mass spectrometry (MS)
      method is capable of measuring high-precision 13CO2 isotope enrichments in
      exhaled breath samples from individuals harboring the H. pylori infection. The
      system exhibited 100% diagnostic sensitivity, and 93% specificity alongside
      positive and negative predictive values of 95% and 100%, respectively, compared
      with invasive endoscopy-based biopsy tests. A statistically sound diagnostic cut
      off value for the presence of H. pylori was determined to be 3.00/00 using a
      receiver operating characteristic curve analysis. The diagnostic accuracy and
      validity of the results are also supported by optical off-axis integrated cavity
      output spectroscopy measurements. The delta13(DOB)C0/00 values of both methods
      correlated well (R2 = 0.9973 at 30 min). The RGA-based instrumental setup
      described here is simple, robust, easy-to-use and more portable and cost
      effective compared to all other currently available detection methods, thus
      making it a new point-of-care medical diagnostic tool for the purpose of large
      scale screening of the H. pylori infection in real time. The RGA-MS technique
      should have broad applicability for 13C-breath tests in a wide range of
      biomedical research and clinical diagnostics for many other diseases and
      metabolic disorders.

PMID- 24566135
TI  - Soluble calreticulin induces tumor necrosis factor-alpha (TNF-alpha) and
      interleukin (IL)-6 production by macrophages through mitogen-activated protein
      kinase (MAPK) and NFkappaB signaling pathways.
AB  - We have recently reported that soluble calreticulin (CRT) accumulates in the sera
      of patients with rheumatoid arthritis or systemic lupus erythematosus. Moreover,
      following self-oligomerization, soluble recombinant CRT (rCRT) polypeptides
      exhibit potent immunostimulatory activities including macrophage activation in
      vitro and antibody induction in vivo. This study was designed to further
      investigate the underlying molecular mechanisms for soluble CRT-induced
      macrophage activation. Treatment of murine macrophages with oligomerized rCRT
      (OrCRT) led to (i) TNF-alpha and IL-6 transcription and protein expression
      without affecting intracellular mRNA stability; and (ii) IkappaBalpha
      degradation, NFkappaB phosphorylation and sustained MAPK phosphorylation in
      cells. Inhibition of IKK and JNK in macrophages substantially abrogated
      production of TNF-alpha and IL-6 induced by OrCRT, while ERK suppression only
      reduced IL-6 expression in parallel experiments. In vitro, fucoidan, a scavenger
      receptor A (SRA)-specific ligand, significantly reduced the uptake of FITC
      labeled OrCRT by macrophages and subsequent MAPK and NFkappaB activation, thereby
      suggesting SRA as one of the potential cell surface receptors for soluble CRT.
      Together, these data indicate that soluble CRT in oligomerized form could play a
      pathogenic role in autoimmune diseases through induction of pro-inflammatory
      cytokines (e.g., TNF-alpha and IL-6) by macrophages via MAPK-NFkappaB signaling
      pathway. 

PMID- 24566136
TI  - Three basic residues of intracellular loop 3 of the beta-1 adrenergic receptor
      are required for golgin-160-dependent trafficking.
AB  - Golgin-160 is a member of the golgin family of proteins, which have been
      implicated in the maintenance of Golgi structure and in vesicle tethering. Golgin
      160 is atypical; it promotes post-Golgi trafficking of specific cargo proteins,
      including the beta-1 adrenergic receptor (beta1AR), a G protein-coupled receptor.
      Here we show that golgin-160 binds directly to the third intracellular loop of
      beta1AR and that this binding depends on three basic residues in this loop.
      Mutation of the basic residues does not affect trafficking of beta1AR from the
      endoplasmic reticulum through the Golgi complex, but results in reduced steady
      state levels at the plasma membrane. We hypothesize that golgin-160 promotes
      incorporation of beta1AR into specific transport carriers at the trans-Golgi
      network to ensure efficient delivery to the cell surface. These results add to
      our understanding of the biogenesis of beta1AR, and suggest a novel point of
      regulation for its delivery to the plasma membrane. 

PMID- 24566137
TI  - HuR and TIA1/TIAL1 are involved in regulation of alternative splicing of SIRT1
      pre-mRNA.
AB  - SIRT1 is a pleiotropic protein that plays critical and multifunctional roles in
      metabolism, senescence, longevity, stress-responses, and cancer, and has become
      an important therapeutic target across a range of diseases. Recent research
      demonstrated that SIRT1 pre-mRNA undergoes alternative splicing to produce
      different isoforms, such as SIRT1 full-length and SIRT1-?Exon8 variants. Previous
      studies revealed these SIRT1 mRNA splice variants convey different
      characteristics and functions to the protein, which may in turn explain the
      multifunctional roles of SIRT1. However, the mechanisms underlying the regulation
      of SIRT1 alternative splicing remain to be elucidated. Our objective is to search
      for new pathways that regulate of SIRT1 alternative splicing. Here we describe
      experiments showing that HuR and TIA1/TIAL1, two kinds of RNA-binding proteins,
      were involved in the regulation of alternative splicing of SIRT1 pre-mRNA under
      normal and stress circumstances: HuR increased SIRT1-?Exon8 by promoting SIRT1
      exon 8 exclusion, whereas TIA1/TIAL1 inhibition of the exon 8 exclusion led to a
      decrease in SIRT1-?Exon8 mRNA levels. This study provides novel insight into how
      the alternative splicing of SIRT1 pre-mRNA is regulated, which has fundamental
      implications for understanding the critical and multifunctional roles of SIRT1. 

PMID- 24566138
TI  - Shape and site dependent in vivo degradation of Mg-Zn pins in rabbit femoral
      condyle.
AB  - A type of specially designed pin model of Mg-Zn alloy was implanted into the full
      thickness of lesions of New Zealand rabbits' femoral condyles. The recovery
      progress, outer surface healing and in vivo degradation were characterized by
      various methods including radiographs, Micro-CT scan with surface rendering, SEM
      (scanning electron microscope) with EDX (Energy Dispersive X-ray analysis) and so
      on. The in vivo results suggested that a few but not sufficient bridges for
      holding force were formed between the bone and the implant if there was a
      preexisting gap between them. The rapid degradation of the implantation in the
      condyle would result in the appearance of cavities. Morphological evaluation of
      the specially designed pins indicated that the cusp was the most vulnerable part
      during degradation. Furthermore, different implantation sites with distinct
      components and biological functions can lead to different degradation rates of Mg
      Zn alloy. The rate of Mg-Zn alloy decreases in the following order: implantation
      into soft tissue, less trabecular bone, more trabecular bone, and cortical bone.
      Because of the complexities of in vivo degradation, it is necessary for the
      design of biomedical Mg-Zn devices to take into consideration the implantation
      sites used in clinics. 

PMID- 24566140
TI  - Autophagic cell death and cancer.
AB  - Programmed cell death (PCD) is a crucial process required for the normal
      development and physiology of metazoans. The three major mechanisms that induce
      PCD are called type I (apoptosis), type II (autophagic cell death), and type III
      (necrotic cell death). Dysfunctional PCD leads to diseases such as cancer and
      neurodegeneration. Although apoptosis is the most common form of PCD, recent
      studies have provided evidence that there are other forms of cell death. One of
      such cell death is autophagic cell death, which occurs via the activation of
      autophagy. The present review summarizes recent knowledge about autophagic cell
      death and discusses the relationship with tumorigenesis. 

PMID- 24566139
TI  - A genotoxic stress-responsive miRNA, miR-574-3p, delays cell growth by
      suppressing the enhancer of rudimentary homolog gene in vitro.
AB  - MicroRNA (miRNA) is a type of non-coding RNA that regulates the expression of its
      target genes by interacting with the complementary sequence of the target mRNA
      molecules. Recent evidence has shown that genotoxic stress induces miRNA
      expression, but the target genes involved and role in cellular responses remain
      unclear. We examined the role of miRNA in the cellular response to X-ray
      irradiation by studying the expression profiles of radio-responsive miRNAs and
      their target genes in cultured human cell lines. We found that expression of miR
      574-3p was induced in the lung cancer cell line A549 by X-ray irradiation.
      Overexpression of miR-574-3p caused delayed growth in A549 cells. A predicted
      target site was detected in the 3'-untranslated region of the enhancer of the
      rudimentary homolog (ERH) gene, and transfected cells showed an interaction
      between the luciferase reporter containing the target sequences and miR-574-3p.
      Overexpression of miR-574-3p suppressed ERH protein production and delayed cell
      growth. This delay was confirmed by knockdown of ERH expression. Our study
      suggests that miR-574-3p may contribute to the regulation of the cell cycle in
      response to X-ray irradiation via suppression of ERH protein production. 

PMID- 24566142
TI  - Dynamin-related protein 1 inhibitors protect against ischemic toxicity through
      attenuating mitochondrial Ca2+ uptake from endoplasmic reticulum store in PC12
      cells.
AB  - Intracellular calcium homeostasis disorder and mitochondrial dysfunction are
      involved in many acute and chronic brain diseases, including ischemic brain
      injury. An imbalance in mitochondrial fission and fusion is one of the most
      important structural abnormalities found in a large number of mitochondrial
      dysfunction related diseases. Here, we investigated the effects of mitochondrial
      division inhibitor A (mdivi A) and mdivi B, two small molecule inhibitors of
      mitochondrial fission protein dunamin-related protein 1 (Drp-1), in neuronal
      injury induced by oxygen-glucose deprivation (OGD) in PC12 cells. We found that
      mdivi A and mdivi B inhibited OGD-induced neuronal injury through attenuating
      apoptotic cell death. These two inhibitors also preserved mitochondrial function,
      as evidenced by reduced reactive oxygen species (ROS) generation and cytochrome c
      release, as well as prevented loss of mitochondrial membrane potential (MMP).
      Moreover, mdivi A and mdivi B significantly suppressed mitochondrial Ca(2+)
      uptake, but had no effect on cytoplasmic Ca(2+) after OGD injury. The results of
      calcium imaging and immunofluorescence staining showed that Drp-1 inhibitors
      attenuated endoplasmic reticulum (ER) Ca(2+) release and prevented ER
      morphological changes induced by OGD. These results demonstrate that Drp-1
      inhibitors protect against ischemic neuronal injury through inhibiting
      mitochondrial Ca(2+) uptake from the ER store and attenuating mitochondrial
      dysfunction.

PMID- 24566141
TI  - Evodiamine induces apoptosis and enhances TRAIL-induced apoptosis in human
      bladder cancer cells through mTOR/S6K1-mediated downregulation of Mcl-1.
AB  - The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), either alone
      or in combination with other anti-cancer agents, has been considered as a new
      strategy for anti-cancer therapy. In this study, we demonstrated that evodiamine,
      a quinolone alkaloid isolated from the fruit of Evodia fructus, induced apoptosis
      and enhanced TRAIL-induced apoptosis in human bladder cancer cells. To elucidate
      the underlying mechanism, we found that evodiamine significantly reduced the
      protein levels of Mcl-1 in 253J and T24 bladder cancer cells, and overexpression
      of this molecule attenuated the apoptosis induced by evodiamine alone, or in
      combination with TRAIL. Further experiments revealed that evodiamine did not
      affect the mRNA level, proteasomal degradation and protein stability of Mcl-1. On
      the other hand, evodiamine inhibited the mTOR/S6K1 pathway, which usually
      regulates protein translation; moreover, knockdown of S6K1 with small interfering
      RNA (siRNA) effectively reduced Mcl-1 levels, indicating evodiamine downregulates
      c-FLIP through inhibition of mTOR/S6K1 pathway. Taken together, our results
      indicate that evodiamine induces apoptosis and enhances TRAIL-induced apoptosis
      possibly through mTOR/S6K1-mediated downregulation of Mcl-1; furthermore, these
      findings provide a rationale for the combined application of evodiamine with
      TRAIL in the treatment of bladder cancer. 

PMID- 24566143
TI  - Pattern recognition techniques applied to the study of leishmanial glyceraldehyde
      3-phosphate dehydrogenase inhibition.
AB  - Chemometric pattern recognition techniques were employed in order to obtain
      Structure-Activity Relationship (SAR) models relating the structures of a series
      of adenosine compounds to the affinity for glyceraldehyde 3-phosphate
      dehydrogenase of Leishmania mexicana (LmGAPDH). A training set of 49 compounds
      was used to build the models and the best ones were obtained with one geometrical
      and four electronic descriptors. Classification models were externally validated
      by predictions for a test set of 14 compounds not used in the model building
      process. Results of good quality were obtained, as verified by the correct
      classifications achieved. Moreover, the results are in good agreement with
      previous SAR studies on these molecules, to such an extent that we can suggest
      that these findings may help in further investigations on ligands of LmGAPDH
      capable of improving treatment of leishmaniasis. 

PMID- 24566144
TI  - A new pepstatin-insensitive thermopsin-like protease overproduced in peptide-rich
      cultures of Sulfolobus solfataricus.
AB  - In this study, we gain insight into the extracellular proteolytic system of
      Sulfolobus solfataricus grown on proteinaceous substrates, providing further
      evidence that acidic proteases were specifically produced in response to peptide
      rich media. The main proteolytic component was the previously isolated SsMTP
      (Sulfolobus solfataricus multi-domain thermopsin-like protease), while the less
      abundant (named SsMTP-1) one was purified, characterized and identified as the
      sso1175 gene-product. The protein revealed a multi-domain organization shared
      with the cognate SsMTP with a catalytic domain followed by several tandemly
      repeated motifs. Moreover, both enzymes were found spread across the
      Crenarchaeota phylum and belonging to the thermopsin family, although segregated
      into diverse phylogenetic clusters. SsMTP-1 showed a 75-kDa molecular mass and
      was stable in the temperature range 50-90  degrees C, with optimal activity at 70
      degrees C and pH 2.0. Serine, metallo and aspartic protease inhibitors did not
      affect the enzyme activity, designating SsMTP-1 as a new member of the pepstatin
      insensitive aspartic protease family. The peptide-bond-specificity of SsMTP-1 in
      the cleavage of the oxidized insulin B chain was uncommon amongst thermopsins,
      suggesting that it could play a distinct, but cooperative role in the protein
      degradation machinery. Interestingly, predictions of the transmembrane protein
      topology of SsMTP and SsMTP-1 strongly suggest a possible contribution in signal
      transduction pathways. 

PMID- 24566145
TI  - Prediction of protein-protein interaction with pairwise kernel support vector
      machine.
AB  - Protein-protein interactions (PPIs) play a key role in many cellular processes.
      Unfortunately, the experimental methods currently used to identify PPIs are both
      time-consuming and expensive. These obstacles could be overcome by developing
      computational approaches to predict PPIs. Here, we report two methods of amino
      acids feature extraction: (i) distance frequency with PCA reducing the dimension
      (DFPCA) and (ii) amino acid index distribution (AAID) representing the protein
      sequences. In order to obtain the most robust and reliable results for PPI
      prediction, pairwise kernel function and support vector machines (SVM) were
      employed to avoid the concatenation order of two feature vectors generated with
      two proteins. The highest prediction accuracies of AAID and DFPCA were 94% and
      93.96%, respectively, using the 10 CV test, and the results of pairwise radial
      basis kernel function are considerably improved over those based on radial basis
      kernel function. Overall, the PPI prediction tool, termed PPI-PKSVM, which is
      freely available at http://159.226.118.31/PPI/index.html, promises to become
      useful in such areas as bio-analysis and drug development. 

PMID- 24566147
TI  - Rationalization of activity cliffs of a sulfonamide inhibitor of DNA
      methyltransferases with induced-fit docking.
AB  - Inhibitors of human DNA methyltransferases (DNMT) are of increasing interest to
      develop novel epi-drugs for the treatment of cancer and other diseases. As the
      number of compounds with reported DNMT inhibition is increasing, molecular
      docking is shedding light to elucidate their mechanism of action and further
      interpret structure-activity relationships. Herein, we present a structure-based
      rationalization of the activity of SW155246, a distinct sulfonamide compound
      recently reported as an inhibitor of human DNMT1 obtained from high-throughput
      screening. We used flexible and induce-fit docking to develop a binding model of
      SW155246 with a crystallographic structure of human DNMT1. Results were in
      excellent agreement with experimental information providing a three-dimensional
      structural interpretation of 'activity cliffs', e.g., analogues of SW155246 with
      a high structural similarity to the sulfonamide compound, but with no activity in
      the enzymatic assay. 

PMID- 24566146
TI  - The neuroprotective role of acupuncture and activation of the BDNF signaling
      pathway.
AB  - Recent studies have been conducted to examine the neuroprotective effects of
      acupuncture in many neurological disorders. Although the neuroprotective effects
      of acupuncture has been linked to changes in signaling pathways, accumulating
      evidence suggest the participation of endogenous biological mediators, such as
      the neurotrophin (NT) family of proteins, specifically, the brain derived
      neurotrophic factor (BDNF). Accordingly, acupuncture can inhibit
      neurodegeneration via expression and activation of BDNF. Moreover, recent studies
      have reported that acupuncture can increase ATP levels at local stimulated
      points. We have also demonstrated that acupuncture could activate monocytes and
      increase the expression of BDNF via the stimulation of ATP. The purpose of this
      article is to review the recent findings and ongoing studies on the
      neuroprotective roles of acupuncture and therapeutic implications of acupuncture
      induced activation of BDNF and its signaling pathway. 

PMID- 24566148
TI  - miR-137: a new player in schizophrenia.
AB  - Schizophrenia is a complex genetic disease and characterized by affective,
      cognitive, neuromorphological, and molecular abnormalities that may have a
      neurodevelopmental origin. MicroRNAs (miRNAs) are critical to neurodevelopment
      and adult neuronal processes by modulating the activity of multiple genes within
      biological networks. MiR-137 as a brain-enriched microRNA, plays important roles
      in regulating embryonic neural stem cells (NSCs) fate determination, neuronal
      proliferation and differentiation, and synaptic maturation. Its dysregulation
      causes changes in the gene expression regulation network of the nervous system,
      thus inducing mental disorders. Recently, miR-137 has been confirmed as a gene
      related to schizophrenia susceptibility. In the following review, we summarize
      the expression pattern, epigenetic regulation and functions of miR-137. A more
      complete picture of the miR-137, which is dysregulated in psychiatric illness,
      may improve our understanding of the molecular mechanisms underlying
      schizophrenia. 

PMID- 24566149
TI  - Characterization of Bactrocera dorsalis serine proteases and evidence for their
      indirect role in insecticide tolerance.
AB  - The oriental fruit fly Bactrocera dorsalis (Hendel) causes devastating losses to
      agricultural crops world-wide and is considered to be an economically important
      pest. Little is known about the digestive enzymes such as serine proteases (SPs)
      in B. dorsalis, which are important both for energy supply and mitigation of
      fitness cost associated with insecticide tolerance. In this study, we identified
      five SP genes in the midgut of B. dorsalis, and the alignments of their deduced
      amino acid sequences revealed the presence of motifs conserved in the SP
      superfamily. Phylogenetic analyses with known SPs from other insect species
      suggested that three of them were trypsin-like proteases. Analyses of the
      expression profiles among the different developmental stages showed that all five
      genes were most abundant in larvae than in other stages. When larvae were
      continuously fed on diet containing 0.33 MUg/g beta-Cypermethrin, expression of
      all five genes were upregulated in the midgut but the larval development was
      delayed. Biochemical assays were consistent with the increased protease activity
      exhibited by SPs in the midgut after treatment with beta-Cypermethrin. Taken
      together, these findings provide evidence for the hypothesis that enhanced SP
      activity may play an indirect role in relieving the toxicity stress of
      insecticide in B. dorsalis. 

PMID- 24566150
TI  - Novel microwave-assisted synthesis of the immunomodulator organotellurium
      compound ammonium trichloro(dioxoethylene-O,O')tellurate (AS101).
AB  - Ammonium trichloro[1,2-ethanediolato-O,O']-tellurate (AS101) is the most
      important synthetic Te compound from the standpoint of its biological activity.
      It is a potent immunomodulator with a variety of potential therapeutic
      applications and antitumoral action in several preclinical and clinical studies.
      An experimental design has been used to develop and optimize a novel microwave
      assisted synthesis (MAOS) of the AS101. In comparison to the results observed in
      the literature, refluxing Te(IV) chloride and ethylene glycol in acetonitrile
      (Method A), or by refluxing Te(IV) chloride and ammonium chloride in ethylene
      glycol (Method B), it was found that the developed methods in the present work
      are an effective alternative, because although performance slightly decreases
      compared to conventional procedures (75% vs. 79% by Method A, and 45% vs. 51% by
      Method B), reaction times decreased from 4 h to 30 min and from 4 h to 10 min, by
      Methods A and B respectively. MAOS is proving to be of value in the rapid
      synthesis of compounds with new and improved biological activities, specially
      based on the benefit of its shorter reaction times. 

PMID- 24566151
TI  - Expression of PHB2 in rat brain cortex following traumatic brain injury.
AB  - Prohibitin2 (PHB2) is a ubiquitous, evolutionarily strongly conserved protein. It
      is one of the components of the prohibitin complex, which comprises two highly
      homologous subunits, PHB1 and PHB2. PHB2 is present in various cellular
      compartments including the nucleus and mitochondria. Recent studies have
      identified PHB2 as a multifunctional protein that controls cell proliferation,
      apoptosis, cristae morphogenesis and the functional integrity of mitochondria.
      However its distribution and function in the central nervous system (CNS) are not
      well understood. In this study, we examined PHB2 expression and cellular
      localization in rats after acute traumatic brain injury (TBI). Western Blot
      analysis showed PHB2 level was significantly enhanced at five days after injury
      compared to control, and then declined during the following days. The protein
      expression of PHB2 was further analyzed by immunohistochemistry. In comparison to
      contralateral cerebral cortex, we observed a highly significant accumulation of
      PHB2 at the ipsilateral brain. Immunofluorescence double-labeling showed that
      PHB2 was co-expressed with NeuN, GFAP. Besides, PHB2 also colocalized with
      activated caspase-3 and PCNA. To further investigate the function of PHB2,
      primary cultured astrocytes and the neuronal cell line PC12 were employed to
      establish a proliferation model and an apoptosis model, respectively, to simulate
      the cell activity after TBI to a certain degree. Knocking down PHB2 by siRNA
      partly increased the apoptosis level of PC12 stimulated by H2O2. While the PHB2
      was interrupted by siRNA, the proliferation level of primary cultured astrocytes
      was inhibited notably than that in the control group. Together with our data, we
      hypothesized that PHB2 might play an important role in CNS pathophysiology after
      TBI. 

PMID- 24566152
TI  - The glutathione peroxidase gene family in Thellungiella salsuginea: genome-wide
      identification, classification, and gene and protein expression analysis under
      stress conditions.
AB  - Glutathione peroxidases (GPX) catalyze the reduction of H2O2 or organic
      hydroperoxides to water or corresponding alcohols using reduced glutathione,
      which plays an essential role in ROS (reactive oxygen species) homeostasis and
      stress signaling. Thellungiella salsuginea (Eutrema salsugineum), a relative of
      Arabidopsis thaliana, displays an extremely high level of tolerance to salt,
      drought, cold and oxidative stresses. The enzymatic antioxidant systems may
      contribute to the stress tolerance of T. salsuginea. In the present study, we
      aimed at understanding the roles of the antioxidant enzymes in T. salsuginea by
      focusing on the GPX family. We identified the eight GPX genes in T. salsuginea,
      and the structure of the N-terminal domains indicated their putative
      chloroplastic, mitochondrial and cytoplasmic location. The exon-intron
      organization of these genes exhibited a conserved pattern among plant GPX genes.
      Multiple environmental stresses and hormone response related cis-acting elements
      were predicted in the promoters of TsGPX genes. The gene and protein expression
      profiles of TsGPXs in response to high level of salinity and osmotic stresses, in
      leaves and roots of T. salsuginea were investigated using real-time RT-PCR and
      western blotting analysis. Our result showed that different members of the GPX
      gene family were coordinately regulated under specific environmental stress
      conditions, and supported the important roles of TsGPXs in salt and drought
      stress response in T. salsuginea. 

PMID- 24566155
TI  - Language, again.

PMID- 24566154
TI  - The stomach cancer pooling (StoP) project: study design and presentation.
AB  - Gastric cancer affects about one million people per year worldwide, being the
      second leading cause of cancer mortality. The study of its etiology remains
      therefore a global issue as it may allow the identification of major targets,
      besides eradication of Helicobacter pylori infection, for primary prevention. It
      has however received little attention, given its comparatively low incidence in
      most high-income countries. We introduce a consortium of epidemiological
      investigations named the 'Stomach cancer Pooling (StoP) Project'. Twenty-two
      studies agreed to participate, for a total of over 9000 cases and 23 000
      controls. Twenty studies have already shared the original data set. Of the
      patients, 40% are from Asia, 43% from Europe, and 17% from North America; 34% are
      women and 66% men; the median age is 61 years; 56% are from population-based case
      control studies, 41% from hospital-based ones, and 3% from nested case-control
      studies derived from cohort investigations. Biological samples are available from
      12 studies. The aim of the StoP Project is to analyze the role of lifestyle and
      genetic determinants in the etiology of gastric cancer through pooled analyses of
      individual-level data. The uniquely large data set will allow us to define and
      quantify the main effects of each risk factor of interest, including a number of
      infrequent habits, and to adequately address associations in subgroups of the
      population, as well as interaction within and between environmental and genetic
      factors. Further, we will carry out separate analyses according to different
      histotypes and subsites of gastric cancer, to identify potential different risk
      patterns and etiological characteristics. 

PMID- 24566153
TI  - C2-ceramide induces cell death and protective autophagy in head and neck squamous
      cell carcinoma cells.
AB  - Ceramides are second messengers involved in several intracellular processes in
      cancer cells, amongst others. The aim of this study was to evaluate the anti
      tumor efficacy of C2-ceramide (C2-Cer; N-acetyl-D-sphingosine) by investigating
      cell death and autophagy in head and neck squamous cell carcinoma (HNSCC) cells.
      C2-Cer showed concentration-dependent cytotoxicity in HN4 and HN30 cell lines. It
      simultaneously induced caspase-3-independent apoptosis and programmed necrosis.
      C2-Cer markedly increased the expression level of microtubule-associated protein
      1 light chain 3B (LC3B) type II associated with protective autophagy. An
      autophagy inhibitor enhanced C2-Cer-mediated cytotoxicity, while a programmed
      necrosis inhibitor produced the opposite effect. Furthermore, C2-Cer up-regulated
      the phosphorylation of extracellular signal-regulated kinase 1/2, but down
      regulated its downstream substrate phospho-mammalian target of rapamycin (p-mTOR)
      during the autophagy process. These results suggested that C2-Cer exerts anti
      tumor effects by inducing programmed apoptosis and necrosis in HNSCC, and these
      cytotoxic effects are enhanced by an autophagy inhibitor. 

PMID- 24566156
TI  - Should a child be discharged from a pediatric practice if the parent refuses
      immunizations?

PMID- 24566159
TI  - Factors affecting Israeli women's decision whether to donate cord blood.
AB  - PURPOSE: To examine whether Israeli mothers' intention to donate cord blood can
      be predicted using the Theory of Planned Behavior (TPB). STUDY DESIGN AND
      METHODS: A descriptive correlation study, employing the TPB. A questionnaire
      constructed based on a literature review of research on cord blood donation and
      on the TPB was administered to 207 Israeli women of childbearing age. RESULTS:
      Behavioral attitudes (women's total appraisal of cord blood donation), subjective
      norms (women's perception of the opinion of significant others regarding the
      specific behavior), and perceived behavioral control (women's total appraisal of
      their control of the behavior and perceived ease or difficulty of cord blood
      donation) were found to predict women's intention to donate cord blood. CLINICAL
      IMPLICATIONS: Since behavioral attitudes, subjective norms, and behavioral
      control can predict cord blood donations, it is important for the medical and
      nursing staff to understand and use these concepts if they hope to obtain women's
      cooperation concerning cord blood donation. Nurses should receive education on
      the subject of cord blood donation, increasing their awareness. It is possible
      that this could lead to a rise in such donations in the future. Both mothers and
      fathers should be consulted about the option of donating cord blood.

PMID- 24566160
TI  - Developing a perinatal memory-making program at a children's hospital.
AB  - Most pregnancies are a time of joy and anticipation, but unfortunately there are
      families who instead suffer one of life's most difficult events: a perinatal
      loss. Although grief processes have some common aspects, grief over a child can
      be especially intense, and those grieving such a loss have unique needs. One of
      the things that nurses can do to assist families in these situations is to assist
      them by creating memories of their child to help ease perinatal grief. This
      article describes the Precious Prints Project, a perinatal memory-making program
      designed to comfort families grieving the loss of a child. We discuss the
      development and implementation of this project, explore the literature, and show
      the strategies used to address the challenges encountered. 

PMID- 24566162
TI  - Perceptions of care in women sent home in latent labor.
AB  - PURPOSE: To assess perceptions of care from woman discharged from an obstetrical
      (OB) triage unit or a labor and delivery unit with a diagnosis of false or latent
      labor in order to determine factors that may increase or decrease the woman's
      satisfaction with care. STUDY DESIGN: Descriptive, convenience sample. METHODS:
      One hundred low-income pregnant women at term presenting for care in latent labor
      consented to participate in a telephone survey. The survey was based on the
      relevant research about care of women in early labor and the Donabedian quality
      improvement framework assessing structure, process, and outcomes of care.
      RESULTS: Forty-one percent of women did not want to be discharged home in latent
      labor. Common reasons included women stating they were in too much pain or they
      were living too far from the birth setting. Eating, drinking, and comfort
      measures were the most common measures women cited that would have made them feel
      better when in the hospital. A reoccurring response from women was their desire
      for very clear and specific written instructions about how to stay comfortable at
      home and when to return to the hospital. CLINICAL IMPLICATIONS: Comfort measures
      in the birth setting, including in triage, should include a variety of options
      including ambulation and oral nutrition. Detailed and specific written
      instructions about early labor and staying comfortable while at home have value
      for women in this survey regarding their perceptions of care. Results from this
      survey of low-income women suggest that a subset of women in latent labor just do
      not want to go home and this may be related to having too much pain and/or travel
      distance to the hospital. Hospital birth settings also have an opportunity to
      create a care environment that provides services and embodies attributes that
      women report as important for their satisfaction with care in latent labor.

PMID- 24566164
TI  - Nutrition as we age.

PMID- 24566165
TI  - Mobile technology for parent tracking of child health.

PMID- 24566166
TI  - Global health literacy.

PMID- 24566168
TI  - Unintended retained foreign objects after surgery and other invasive procedures.

PMID- 24566169
TI  - Specific changes of gut commensal microbiota and TLRs during indomethacin-induced
      acute intestinal inflammation in rats.
AB  - BACKGROUND AND AIMS: Gut microbiota is a contributing factor in the development
      and maintenance of intestinal inflammation, although precise cause-effect
      relationships have not been established. We assessed spontaneous changes of gut
      commensal microbiota and toll-like receptors (TLRs)-mediated host-bacterial
      interactions in a model of indomethacin-induced acute enteritis in rats. METHODS:
      Male Spague-Dawley rats, maintained under conventional conditions, were used.
      Enteritis was induced by systemic indomethacin administration. During the acute
      phase of inflammation, animals were euthanized and ileal and ceco-colonic changes
      evaluated. Inflammation was assessed through disease activity parameters
      (clinical signs, macroscopic/microscopic scores and tissue levels of inflammatory
      markers). Microbiota (ileal and ceco-colonic) was characterized using fluorescent
      in situ hybridization (FISH) and analysis of 16s rDNA polymorphism. Host
      bacterial interactions were assessed evaluating the ratio of bacterial adherence
      to the intestinal wall (FISH) and expression of TLRs 2 and 4 (RT-PCR). RESULTS:
      After indomethacin, disease activity parameters increased, suggesting an active
      inflammation. Total bacterial counts were similar in vehicle- or indomethacin
      treated animals. However, during inflammation the relative composition of the
      microbiota was altered. This dysbiotic state was characterized by an increase in
      the counts of Bacteroides spp., Enterobacteriaceae (in ileum and cecum-colon) and
      Clostridium spp. (in ileum). Bacterial wall adherence significantly increased
      during inflammation. In animals with enteritis, TLR-2 and -4 were up-regulated
      both in the ileum and the ceco-colonic region. CONCLUSIONS: Gut inflammation
      implies qualitative changes in GCM, with simultaneous alterations in host
      bacterial interactions. These observations further support a potential role for
      gut microbiota in the pathophysiology of intestinal inflammation.

PMID- 24566170
TI  - A prospective evaluation of the predictive value of faecal calprotectin in
      quiescent Crohn's disease.
AB  - BACKGROUND: Faecal calprotectin (FC) is a non-invasive marker of gastrointestinal
      inflammation. AIM: To determine whether higher FC levels in individuals with
      quiescent Crohn's disease are associated with clinical relapse over the ensuing
      12 months. METHODS: A single centre prospective study was undertaken in Crohn's
      disease patients in clinical remission. The receiver operating characteristic
      (ROC) curve for the primary endpoint of clinical relapse by 12 months, based on
      FC at baseline, was calculated. Kaplan-Meier curves of time to relapse were based
      on the resulting optimal FC cutoff for predicting relapse. RESULTS: Of 97
      patients recruited, 92 were either followed up for 12 months without relapsing,
      or reached the primary endpoint within that period. Of these, 10 (11%) relapsed
      by 12 months. Median FC was lower for non-relapsers, 96 MUg/g (IQR 39-237), than
      for relapsers, 414 MUg/g (IQR 259-590), (p=0.005). The area under the ROC curve
      to predict relapse using FC was 77.4%. An optimal cutoff FC value of 240 MUg/g to
      predict relapse had sensitivity of 80.0% and specificity of 74.4%. Negative
      predictive value was 96.8% and positive predictive value was 27.6%, FC >=240
      MUg/g was associated with likelihood of relapse by 12-months 12.18 (95% CI 2.55
      58.2) times higher than lower values (p=0.002). CONCLUSIONS: In this prospective
      dataset, FC is a useful tool to help identify quiescent Crohn's disease patients
      at a low risk of relapse over the ensuing 12 months. FC of 240 MUg/g was the
      optimal cutoff in this cohort.

PMID- 24566171
TI  - First report of KPC-2 Carbapenemase-producing Klebsiella pneumoniae in Japan.
AB  - We investigated a novel Japanese isolate of sequence type 11 (ST11), the
      Klebsiella pneumoniae carbapenemase-2 (KPC-2)-producing K. pneumoniae strain
      Kp3018, which was previously obtained from a patient treated at a Brazilian
      hospital. This strain was resistant to various antibiotic classes, including
      carbapenems, and harbored the gene blaKPC-2, which was present on the
      transferable plasmid of ca. 190 kb, in addition to the blaCTX-M-15 gene.
      Furthermore, the ca. 2.3-kb sequences (ISKpn8-blaKPC-2-ISKpn6-like), encompassing
      blaKPC-2, were found to be similar to those of K. pneumoniae strains from China. 

PMID- 24566172
TI  - Doripenem, gentamicin, and colistin, alone and in combinations, against
      gentamicin-susceptible, KPC-producing Klebsiella pneumoniae strains with various
      ompK36 genotypes.
AB  - Gentamicin doses of 2 and 10 MUg/ml were bactericidal against 64% and 100%,
      respectively, of gentamicin-susceptible KPC-2-producing Klebsiella pneumoniae
      strains. Treatment with the combination of doripenem (8 MUg/ml) plus colistin (2
      MUg/ml) was inferior to treatment with gentamicin (2 MUg/ml), doripenem
      gentamicin, gentamicin-colistin, and doripenem-gentamicin-colistin against
      strains with glycine and aspartic acid insertions in OpmK36 porin at amino acid
      (aa) positions 134 and 135 (n = 9). Doripenem-colistin was comparable to other 2-
      or 3-drug regimens and superior to single drugs against wild-type/minor ompK36
      mutants (n = 5). An algorithm incorporating ompK36 genotypes and susceptibility
      to gentamicin and doripenem may predict antimicrobial activity against KPC
      producing K. pneumoniae. 

PMID- 24566173
TI  - Agp2p, the plasma membrane transregulator of polyamine uptake, regulates the
      antifungal activities of the plant defensin NaD1 and other cationic peptides.
AB  - Cationic antifungal peptides (AFPs) act through a variety of mechanisms but share
      the common feature of interacting with the fungal cell surface. NaD1, a defensin
      from Nicotiana alata, has potent antifungal activity against a variety of fungi
      of both hyphal and yeast morphologies. The mechanism of action of NaD1 occurs via
      three steps: binding to the fungal cell surface, permeabilization of the plasma
      membrane, and internalization and interaction with intracellular targets to
      induce fungal cell death. The targets at each of these three stages have yet to
      be defined. In this study, the screening of a Saccharomyces cerevisiae deletion
      collection led to the identification of Agp2p as a regulator of the potency of
      NaD1. Agp2p is a plasma membrane protein that regulates the transport of
      polyamines and other molecules, many of which carry a positive charge. Cells
      lacking the agp2 gene were more resistant to NaD1, and this resistance was
      accompanied by a decreased uptake of defensin. Agp2p senses and regulates the
      uptake of the polyamine spermidine, and competitive inhibition of the antifungal
      activity of NaD1 by spermidine was observed in both S. cerevisiae and the plant
      pathogen Fusarium oxysporum. The resistance of agp2Delta cells to other cationic
      antifungal peptides and decreased binding of the cationic protein cytochrome c to
      agp2Delta cells compared to that of wild-type cells have led to a proposed
      mechanism of resistance whereby the deletion of agp2 leads to an increase in
      positively charged molecules at the cell surface that repels cationic antifungal
      peptides. 

PMID- 24566174
TI  - NBTI 5463 is a novel bacterial type II topoisomerase inhibitor with activity
      against gram-negative bacteria and in vivo efficacy.
AB  - The need for new antibiotics that address serious Gram-negative infections is
      well recognized. Our efforts with a series of novel bacterial type II
      topoisomerase inhibitors (NBTIs) led to the discovery of NBTI 5463, an agent with
      improved activity over other NBTIs against Gram-negative bacteria, in particular
      against Pseudomonas aeruginosa (F. Reck, D. E. Ehmann, T. J. Dougherty, J. V.
      Newman, S. Hopkins, G. Stone, N. Agrawal, P. Ciaccio, J. McNulty, H. Barthlow, J.
      O'Donnell, K. Goteti, J. Breen, J. Comita-Prevoir, M. Cornebise, M. Cronin, C. J.
      Eyermann, B. Geng, G. R. Carr, L. Pandarinathan, X. Tang, A. Cottone, L. Zhao, N.
      Bezdenejnih-Snyder, submitted for publication). In the present work, NBTI 5463
      demonstrated promising activity against a broad range of Gram-negative pathogens.
      In contrast to fluoroquinolones, the compound did not form a double-strand DNA
      cleavable complex with Escherichia coli DNA gyrase and DNA, but it was a potent
      inhibitor of both DNA gyrase and E. coli topoisomerase IV catalytic activities.
      In studies with P. aeruginosa, NBTI 5463 was bactericidal. Resistant mutants
      arose at a low rate, and the mutations were found exclusively in the nfxB gene, a
      regulator of the MexCD-OprJ efflux system. Levofloxacin-selected resistance
      mutations in GyrA did not result in decreased susceptibility to NBTI 5463. Animal
      infection studies demonstrated that NBTI 5463 was efficacious in mouse models of
      lung, thigh, and ascending urinary tract infections. 

PMID- 24566175
TI  - Fluoroquinolone-resistant Escherichia coli sequence type 131 isolates causing
      bloodstream infections in a canadian region with a centralized laboratory system:
      rapid emergence of the H30-Rx sublineage.
AB  - A population-based surveillance study was designed to describe the clinical
      features and characteristics of sequence type 131 (ST131) and its H30 and H30-Rx
      sublineages among fluoroquinolone-resistant (FQ-R) Escherichia coli isolates that
      caused bloodstream infections (BSIs) in a Canadian region with a centralized
      laboratory system over an 11-year period (2000 to 2010). Nonrepeat isolates from
      true incident cases were included. Established PCR methods were used to define
      ST131, its H30 and H30-Rx sublineages, extended-spectrum beta-lactamase and AmpC
      production, and plasmid-mediated quinolone resistance determinants. A total of
      677 Calgary residents with incident BSIs due to FQ-R E. coli were identified; the
      majority presented with health care-associated upper urinary tract infections
      (UTIs). There was a rise in FQ-R over the 11-year period because of an increase
      in ST131 toward the end of the study period (2008 to 2010) that was due to a
      rapid influx of the H30-Rx sublineage. We identified the association of H30-Rx
      with primary sepsis, upper UTIs as a complication of prostate biopsies, multidrug
      resistance, and the presence of blaCTX-M-15 and aac(6')-lb-cr. E. coli ST131 H30
      Rx has established itself as a major drug-resistant sublineage in Calgary, posing
      an important new public health threat within our region. We urgently need well
      designed epidemiological and molecular studies to further understand the dynamics
      of transmission, risk factors, and reservoirs of H30-Rx. 

PMID- 24566176
TI  - Complete nucleotide sequences of two blaKPC-2-bearing IncN Plasmids isolated from
      sequence type 442 Klebsiella pneumoniae clinical strains four years apart.
AB  - We sequenced the oldest blaKPC-2-bearing plasmid isolated in Brazil and another
      plasmid also carried by a Klebsiella pneumoniae strain of sequence type 442
      (ST442), isolated 52 months later. Both plasmids present an IncN backbone and few
      acquired regions. Because the 2005 plasmid presented deletions and a truncated
      gene within Tn4401b compared to the 2009 plasmid, we can thus infer that IncN
      blaKPC-2-bearing plasmids pFCF1305 and pFCF3SP had a common ancestor circulating
      in Brazil prior to May 2005. 

PMID- 24566177
TI  - Identification of CMY-2-type cephalosporinases in clinical isolates of
      Enterobacteriaceae by MALDI-TOF MS.
AB  - This study exploited the possibility to detect Citrobacter freundii-derived CMY-2
      like cephalosporinases in Enterobacteriaceae clinical isolates using matrix
      assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF
      MS). Periplasmic proteins were prepared using a modified sucrose method and
      analyzed by MALDI-TOF MS. A ca. 39,850-m/z peak, confirmed to represent a C.
      freundii-like beta-lactamase by in-gel tryptic digestion followed by MALDI
      TOF/TOF MS, was observed only in CMY-producing isolates. We have also shown the
      potential of the assay to detect ACC- and DHA-like AmpC-type beta-lactamases. 

PMID- 24566178
TI  - Pharmacokinetic and safety analyses of tenofovir and tenofovir-emtricitabine
      vaginal tablets in pigtailed macaques.
AB  - Vaginal rapidly disintegrating tablets (RDTs) containing tenofovir (TFV) or TFV
      and emtricitabine (FTC) were evaluated for safety and pharmacokinetics in
      pigtailed macaques. Two separate animal groups (n = 4) received TFV (10 mg) or
      TFV-FTC (10 mg each) RDTs, administered near the cervix. A third group (n = 4)
      received 1 ml TFV gel. Blood plasma, vaginal tissue biopsy specimens, and vaginal
      fluids were collected before and after product application at 0, 0.5, 1, 4, and
      24 h. A disintegration time of <30 min following vaginal application of the RDTs
      was noted, with negligible effects on local inflammatory cytokines, vaginal pH,
      and microflora. TFV pharmacokinetics were generally similar for both RDTs and
      gel, with peak median concentrations in vaginal tissues and vaginal secretions
      being on the order of 10(4) to 10(5) ng/g (147 to 571 MUM) and 10(6) ng/g (12 to
      34 mM), respectively, at 1 to 4 h postdose. At 24 h, however, TFV vaginal tissue
      levels were more sustained after RDT dosing, with median TFV concentrations being
      approximately 1 log higher than those with gel dosing. FTC pharmacokinetics after
      combination RDT dosing were similar to those of TFV, with peak median vaginal
      tissue and fluid levels being on the order of 10(4) ng/g (374 MUM) and 10(6) ng/g
      (32 mM), respectively, at 1 h postdose with levels in fluid remaining high at 24
      h. RDTs are a promising alternative vaginal dosage form, delivering TFV and/or
      FTC at levels that would be considered inhibitory to simian-human
      immunodeficiency virus in the macaque vaginal microenvironment over a 24-h
      period. 

PMID- 24566180
TI  - N-acylated derivatives of sulfamethoxazole and sulfafurazole inhibit
      intracellular growth of Chlamydia trachomatis.
AB  - Antibacterial compounds with novel modes of action are needed for management of
      bacterial infections. Here we describe a high-content screen of 9,800 compounds
      identifying acylated sulfonamides as novel growth inhibitors of the sexually
      transmitted pathogen Chlamydia trachomatis. The effect was bactericidal and
      distinct from that of sulfonamide antibiotics, as para-aminobenzoic acid did not
      reduce efficacy. Chemical inhibitors play an important role in Chlamydia research
      as probes of potential targets and as drug development starting points. 

PMID- 24566179
TI  - Plant-derived decapeptide OSIP108 interferes with Candida albicans biofilm
      formation without affecting cell viability.
AB  - We previously identified a decapeptide from the model plant Arabidopsis thaliana,
      OSIP108, which is induced upon fungal pathogen infection. In this study, we
      demonstrated that OSIP108 interferes with biofilm formation of the fungal
      pathogen Candida albicans without affecting the viability or growth of C.
      albicans cells. OSIP108 displayed no cytotoxicity against various human cell
      lines. Furthermore, OSIP108 enhanced the activity of the antifungal agents
      amphotericin B and caspofungin in vitro and in vivo in a Caenorhabditis elegans
      C. albicans biofilm infection model. These data point to the potential use of
      OSIP108 in combination therapy with conventional antifungal agents. In a first
      attempt to unravel its mode of action, we screened a library of 137 homozygous C.
      albicans mutants, affected in genes encoding cell wall proteins or transcription
      factors important for biofilm formation, for altered OSIP108 sensitivity. We
      identified 9 OSIP108-tolerant C. albicans mutants that were defective in either
      components important for cell wall integrity or the yeast-to-hypha transition. In
      line with these findings, we demonstrated that OSIP108 activates the C. albicans
      cell wall integrity pathway and that its antibiofilm activity can be blocked by
      compounds inhibiting the yeast-to-hypha transition. Furthermore, we found that
      OSIP108 is predominantly localized at the C. albicans cell surface. These data
      point to interference of OSIP108 with cell wall-related processes of C. albicans,
      resulting in impaired biofilm formation. 

PMID- 24566181
TI  - Characterization of blaOXA-143 variants in Acinetobacter baumannii and
      Acinetobacter pittii.
AB  - The acquired carbapenem-hydrolyzing oxacillinase (OXA) OXA-143 has thus far been
      detected only in Acinetobacter baumannii isolates from Brazil. The aim of this
      study was to characterize three OXA-143 variants: OXA-231 and OXA-253 from
      carbapenem-resistant A. baumannii isolates and OXA-255 in a carbapenem
      susceptible Acinetobacter pittii isolate originating from Brazil, Honduras, and
      the United States, respectively. The 5' rapid amplification of cDNA ends (RACE)
      technique identified the same transcription initiation site for all blaOXA-143
      like genes and revealed differences in the putative promoter regions. However,
      all cloned OXA-143 variants conferred carbapenem resistance on A. baumannii ATCC
      17978 and OXA-255 conferred carbapenem resistance on A. pittii SH024, which was
      correlated with blaOXA-255 gene expression. This is the first description of OXA
      143-like outside A. baumannii. Detection of OXA-143-like in the United States and
      Honduras indicates its dissemination through the American continent. 

PMID- 24566182
TI  - The emergence of linezolid resistance among Enterococci in intestinal microbiota
      of treated patients is unrelated to individual pharmacokinetic characteristics.
AB  - Linezolid is an antimicrobial agent for the treatment of multiresistant Gram
      positive infections. We assessed the impact of linezolid on the microbiota and
      the emergence of resistance and investigated its relationship with plasma
      pharmacokinetics of the antibiotic. Twenty-eight patients were treated for the
      first time with linezolid administered orally (n = 17) or parenterally (n = 11)
      at 600 mg twice a day. Linezolid plasma pharmacokinetic analysis was performed on
      day 7. Colonization by fecal enterococci, pharyngeal streptococci, and nasal
      staphylococci were assessed using selective media with or without supplemental
      linezolid. The resistance to linezolid was characterized. The treatment led to a
      decrease of enterococci, staphylococci, and streptococci in the fecal (P = 0.03),
      nasal, and pharyngeal (P < 0.01) microbiotas. The appearance of resistant strains
      was observed only in enterococci from the fecal microbiota between the 7th and
      21st days of treatment in four patients (14.3%). The resistance was mainly due
      for the first time to the mutation G2447T in the 23S rRNA gene. No
      pharmacokinetic parameters were significantly different between the patients,
      regardless of the appearance of resistance. The emergence of linezolid resistance
      during treatment was observed only in the intestinal microbiota and unrelated to
      pharmacokinetic parameters. However, colonization by Gram-positive bacteria was
      reduced as a result of treatment in all microbiotas. 

PMID- 24566183
TI  - Intrapulmonary posaconazole penetration at the infection site in an
      immunosuppressed murine model of invasive pulmonary aspergillosis receiving oral
      prophylactic regimens.
AB  - Adequate penetration to the infection/colonization site is crucial to attain
      optimal efficacy of posaconazole against Aspergillus fumigatus diseases. We
      evaluated posaconazole exposure in pulmonary epithelial lining fluid (ELF) in a
      murine model of invasive pulmonary aspergillosis. The posaconazole exposure (area
      under the plasma concentration-time curve from time zero to 24 h postinfusion
      [AUC0-24]) in ELF was 20% to 31% of that in plasma for total drug after the third
      dose, and the relationship between plasma and ELF exposure was linear (r(2) =
      0.97, P = 0.016). 

PMID- 24566184
TI  - Novel liquid chromatography-tandem mass spectrometry method for simultaneous
      detection of anti-HIV drugs Lopinavir, Ritonavir, and Tenofovir in plasma.
AB  - For HIV infection, anti-HIV drug combinations are typically used as highly active
      antiretroviral therapy (HAART), intended to maximize viral suppression. Three
      drugs used frequently in combination are the protease inhibitors lopinavir and
      ritonavir and the nucleotide reverse transcriptase inhibitor tenofovir. We have
      successfully developed a simple, efficient, and sensitive method to
      simultaneously extract and determine the concentrations of lopinavir, ritonavir,
      and tenofovir in plasma samples. The plasma extractions were performed using a
      liquid-liquid extraction followed by protein precipitation of the remaining
      aqueous layer. The collected fractions were combined, dried, and reconstituted in
      the mobile phase. The drugs were quantified using liquid chromatography coupled
      with tandem mass spectrometry. The assay was applied to a study of plasma drug
      levels in two primates (Macaca nemestrina). The bioanalytical assay was optimized
      and validated to exhibit a high extraction efficiency and good sensitivity and
      reproducibility. When the assay was applied in a primate study, all three drugs
      could be detected in plasma within minutes of subcutaneous dosing. This validated
      assay will be useful for evaluation of drug concentrations in an efficient,
      selective, and sensitive manner. 

PMID- 24566185
TI  - Fitness costs for Influenza B viruses carrying neuraminidase inhibitor-resistant
      substitutions: underscoring the importance of E119A and H274Y.
AB  - Influenza B viruses cause annual outbreaks of respiratory illness in humans and
      are increasingly recognized as a major cause of influenza-associated pediatric
      mortality. Neuraminidase (NA) inhibitors (NAIs) are the only available therapy
      for patients infected with influenza B viruses, and the potential emergence of
      NAI-resistant viruses is a public health concern. The NA substitutions located
      within the enzyme active site could not only reduce NAI susceptibility of
      influenza B virus but also affect virus fitness. In this study, we investigated
      the effect of single NA substitutions on the fitness of influenza
      B/Yamanashi/166/1998 viruses (Yamagata lineage). We generated recombinant viruses
      containing either wild-type (WT) NA or NA with a substitution in the catalytic
      (R371K) or framework (E119A, D198E, D198Y, I222T, H274Y, and N294S) residues. We
      assessed NAI susceptibility, NA biochemical properties, NA protein expression,
      and virus replication in vitro and in differentiated normal human bronchial
      epithelial (NHBE) cells. Our results showed that four NA substitutions (D198E,
      I222T, H274Y, and N294S) conferred reduced inhibition by oseltamivir and three
      (E119A, D198Y, and R371K) conferred highly reduced inhibition by oseltamivir,
      zanamivir, and peramivir. All NA substitutions, except for D198Y and R371K, were
      genetically stable after seven passages in MDCK cells. Cell surface NA protein
      expression was significantly increased by H274Y and N294S substitutions. Viruses
      with the E119A, I222T, H274Y, or N294S substitution were not attenuated in
      replication efficiency in vitro or in NHBE cells. Overall, viruses with the E119A
      or H274Y NA substitution possess fitness comparable to NAI-susceptible virus, and
      the acquisition of these substitutions by influenza B viruses should be closely
      monitored. 

PMID- 24566186
TI  - Activities of fluconazole, caspofungin, anidulafungin, and amphotericin B on
      planktonic and biofilm Candida species determined by microcalorimetry.
AB  - We investigated the activities of fluconazole, caspofungin, anidulafungin, and
      amphotericin B against Candida species in planktonic form and biofilms using a
      highly sensitive assay measuring growth-related heat production
      (microcalorimetry). C. albicans, C. glabrata, C. krusei, and C. parapsilosis were
      tested, and MICs were determined by the broth microdilution method. The
      antifungal activities were determined by isothermal microcalorimetry at 37
      degrees C in RPMI 1640. For planktonic Candida, heat flow was measured in the
      presence of antifungal dilutions for 24 h. Candida biofilm was formed on porous
      glass beads for 24 h and exposed to serial dilutions of antifungals for 24 h, and
      heat flow was measured for 48 h. The minimum heat inhibitory concentration (MHIC)
      was defined as the lowest antifungal concentration reducing the heat flow peak by
      >=50% (>=90% for amphotericin B) at 24 h for planktonic Candida and at 48 h for
      Candida biofilms (measured also at 24 h). Fluconazole (planktonic MHICs, 0.25 to
      >512 MUg/ml) and amphotericin B (planktonic MHICs, 0.25 to 1 MUg/ml) showed
      higher MHICs than anidulafungin (planktonic MHICs, 0.015 to 0.5 MUg/ml) and
      caspofungin (planktonic MHICs, 0.125 to 0.5 MUg/ml). Against Candida species in
      biofilms, fluconazole's activity was reduced by >1,000-fold compared to its
      activity against the planktonic counterparts, whereas echinocandins and
      amphotericin B mainly preserved their activities. Fluconazole induced growth of
      planktonic C. krusei at sub-MICs. At high concentrations of caspofungin (>4
      MUg/ml), paradoxical growth of planktonic C. albicans and C. glabrata was
      observed. Microcalorimetry enabled real-time evaluation of antifungal activities
      against planktonic and biofilm Candida organisms. It can be used in the future to
      evaluate new antifungals and antifungal combinations and to study resistant
      strains. 

PMID- 24566188
TI  - Identification of Cryptosporidium parvum active chemical series by Repurposing
      the open access malaria box.
AB  - The apicomplexan parasites Cryptosporidium parvum and Cryptosporidium hominis are
      major etiologic agents of human cryptosporidiosis. The infection is typically
      self-limited in immunocompetent adults, but it can cause chronic fulminant
      diarrhea in immunocompromised patients and malnutrition and stunting in children.
      Nitazoxanide, the current standard of care for cryptosporidiosis, is only
      partially efficacious for children and is no more effective than a placebo for
      AIDS patients. Unfortunately, financial obstacles to drug discovery for diseases
      that disproportionately affect low-income countries and technical limitations
      associated with studies of Cryptosporidium biology impede the development of
      better drugs for treating cryptosporidiosis. Using a cell-based high-throughput
      screen, we queried the Medicines for Malaria Venture (MMV) Open Access Malaria
      Box for activity against C. parvum. We identified 3 novel chemical series derived
      from the quinolin-8-ol, allopurinol-based, and 2,4-diamino-quinazoline chemical
      scaffolds that exhibited submicromolar potency against C. parvum. Potency was
      conserved in a subset of compounds from each scaffold with varied physicochemical
      properties, and two of the scaffolds identified exhibit more rapid inhibition of
      C. parvum growth than nitazoxanide, making them excellent candidates for further
      development. The 2,4-diamino-quinazoline and allopurinol-based compounds were
      also potent growth inhibitors of the related apicomplexan parasite Toxoplasma
      gondii, and a good correlation was observed in the relative activities of the
      compounds in the allopurinol-based series against T. gondii and C. parvum. Taken
      together, these data illustrate the utility of the Open Access Malaria Box as a
      source of both potential leads for drug development and chemical probes to
      elucidate basic biological processes in C. parvum and other apicomplexan
      parasites. 

PMID- 24566189
TI  - Activity of host antimicrobials against multidrug-resistant Acinetobacter
      baumannii acquiring colistin resistance through loss of lipopolysaccharide.
AB  - Acinetobacter baumannii can acquire resistance to the cationic peptide antibiotic
      colistin through complete loss of lipopolysaccharide (LPS) expression. The
      activities of the host cationic antimicrobials LL-37 and human lysozyme against
      multidrug-resistant clinical isolates of A. baumannii that acquired colistin
      resistance through lipopolysaccharide loss were characterized. We demonstrate
      that LL-37 has activity against strains lacking lipopolysaccharide that is
      similar to that of their colistin-sensitive parent strains, whereas human
      lysozyme has increased activity against colistin-resistant strains lacking LPS. 

PMID- 24566187
TI  - In vitro assessment and multicenter cohort study of comparative nephrotoxicity
      rates associated with colistimethate versus polymyxin B therapy.
AB  - Despite concerns of nephrotoxicity, polymyxin antibiotics often remain the only
      susceptible agents for multidrug-resistant (MDR) Gram-negative bacteria. Colistin
      has been more commonly used clinically due to a perceived safety benefit. We
      compared the nephrotoxicity of colistin to polymyxin B. The in vitro cytotoxicity
      of colistin was compared to polymyxin B in two mammalian renal cell lines. To
      validate the clinical relevance of the findings, we evaluated adult patients with
      normal renal function who received a minimum of 72 h of polymyxin therapy in a
      multicenter study. The primary outcome was the prevalence of nephrotoxicity, as
      defined by the RIFLE (risk, injury, failure, loss, end-stage kidney disease)
      criteria. Colistin exhibited an in vitro cytotoxicity profile similar to
      polymyxin B. A total of 225 patients (121 receiving colistimethate, 104 receiving
      polymyxin B) were evaluated. Independent risk factors for colistimethate
      associated nephrotoxicity included age (odds ratio [OR], 1.04; 95% confidence
      interval [CI], 1.00 to 1.07; P = 0.03), duration of therapy (OR 1.08; 95% CI,
      1.02 to 1.15; P = 0.02), and daily dose by ideal body weight (OR 1.40; 95% CI,
      1.05 to 1.88; P = 0.02). In contrast, cystic fibrosis was found to be a
      protective factor in patients who received colistimethate (OR, 0.03; 95% CI,
      0.001 to 0.79; P = 0.04). In a matched analysis based on the risk factors
      identified (n = 76), the prevalence of nephrotoxicity was higher with
      colistimethate than with polymyxin B (55.3% versus 21.1%; P = 0.004). Polymyxin B
      was not found to be more nephrotoxic than colistin and may be the preferred
      polymyxin for MDR infections. A prospective study comparing the two polymyxins
      directly is warranted. 

PMID- 24566192
TI  - Histopathological and molecular insights into the ovicidal activities of two
      entomopathogenic fungi against two-spotted spider mite.
AB  - Entomopathogenic fungi can infect and kill spider mite eggs but their ovicidal
      activities are poorly understood. Here we gain histopathogenical and molecular
      insights into the ovicidal activities of Beauveria bassiana and Isaria
      fumosorosea against the two-spotted spider mite, Tetranychus urticae. Scanning
      electronic microscopy indicated successful adhesion and germination of fungal
      conidia on egg shell at 24h post-spray (HPS). Germ tubes of both fungi could
      penetrate into egg shell with penetration pegs at 48 HPS. Interestingly, the germ
      tubes of B. bassiana may elongate on egg surface to locate appropriate sites for
      penetration, acting as 'searching' hyphae. Aside from the normal penetration, the
      germ tubes of I. fumosorosea can be completely or partially embedded into egg
      shell for a distance of extension, forming shell humps. Light microscopy of
      ultrathin sections of infected eggs showed shrunken (affected) or disrupted
      embryos at 48-96 HPS despite little effect on egg cleavage at 24 HPS. However,
      distinguishable hyphal cells were hardly found inside the embryos lacking oxygen
      although fungal outgrowths were abundant on unhatched (killed) eggs. In PCR with
      specific probes, the 18S rDNA signals of B. bassiana (412 bp) and I. fumosorosea
      (454 bp) in the DNA extracts from surface-cleaned mite eggs increased at 0-96
      HPS, confirming fungal colonization in the infected eggs. We consider that the
      colonization on shell surface and underside could rely upon extending hyphae for
      uptake of egg nutrition, resulting in embryo disruption. Our observations add
      knowledge to microbial control of spider mites.

PMID- 24566191
TI  - Areospora rohanae n.gen. n.sp. (Microsporidia; Areosporiidae n. fam.) elicits
      multi-nucleate giant-cell formation in southern king crab (Lithodes santolla).
AB  - This paper utilises histological, ultrastructure and molecular phylogenetic data
      to describe a novel genus and species (Areospora rohanae n.gen., n.sp.) within
      the phylum Microsporidia. Phylogenetic and morphological distinction from other
      known lineages within the phylum also provide strong support for erection of a
      new family (Areosporiidae n. fam) to contain the parasite. Recognised via lesions
      observed by workers in king crab processing facilities in southern Chile, the
      parasite elicits giant cell formation in infected crabs. Merogony within
      haemocytes and fixed phagocytes proceeds apparent fusion of infected cells to
      produce multinucleate syncitia in which further development of the parasite
      occurs. Subsequent recruitment of adjacent cells within the haemal spaces of the
      hepatopancreas, the podocytes of the gill, and particularly in the subcuticular
      connective tissues, characterises the pathogenesis of A. rohanae. In late stages
      of infection, significant remodelling of the subcuticular tissues corresponds to
      the clinical lesions observed within processing plants. Sporogony of A. rohanae
      also occurs within the syncitial cytoplasm and culminates in production of
      bizarre spores, ornamented with distinctive tubular bristles. Spores occur in
      sets of 8 within a sporophorous vesicle. The description of A. rohanae offers
      considerable insight into the pathogenesis of giant-cell forming Microsporidia,
      signifies a new lineage of giant-cell forming Microsporidia in marine hosts, and
      may reflect emergence of a commercially-significant pathogen in the southern
      ocean Lithodes santolla fishery. 

PMID- 24566193
TI  - Arterial stiffness and blood flow adaptations following eight weeks of resistance
      exercise training in young and older women.
AB  - Resistance training is recommended for all adults of both sexes. The arterial
      stiffness and limb blood flow responses to resistance training in young and older
      women have not been well-studied. The purpose of this study was to examine
      arterial stiffness and blood flow adaptations to high-intensity resistance
      exercise training in young and older women. Young (aged 18-25) and older (aged 50
      64) women performed full-body high-intensity resistance exercise three times per
      week for eight weeks. The following measurements were performed twice prior to
      training and once following training: carotid to femoral and femoral to tibialis
      posterior pulse wave velocity (PWV), blood pressure, heart rate, resting forearm
      blood flow and forearm reactive hyperemia. Data was analyzed by ANOVAs with alpha
      set at 0.05. Correlations were also examined between changes in arterial
      stiffness and baseline arterial stiffness values. Older subjects had higher
      carotid-femoral PWV than younger subjects. No significant effects were found for
      femoral-tibialis posterior PWV or for resting forearm blood flow. Changes in
      carotid-femoral and femoral-tibialis posterior PWV correlated significantly with
      their respective baseline values. Older subjects increased peak forearm blood
      flow while young subjects showed no change. Total hyperemia increased
      significantly in both groups. In conclusion, in both young and older women, eight
      weeks of high-intensity resistance training appeared to improve microvascular
      forearm function while not changing carotid-femoral or femoral-tibialis posterior
      arterial stiffness. However, a large degree of individual variation was found and
      arterial stiffness adaptations appeared positively related to the initial
      stiffness values. 

PMID- 24566194
TI  - Automated patient-specific classification of long-term Electroencephalography.
AB  - This paper presents a novel systematic approach for patient-specific
      classification of long-term Electroencephalography (EEG). The goal is to extract
      the seizure sections with a high accuracy to ease the Neurologist's burden of
      inspecting such long-term EEG data. We aim to achieve this using the minimum
      feedback from the Neurologist. To accomplish this, we use the majority of the
      state-of-the-art features proposed in this domain for evolving a collective
      network of binary classifiers (CNBC) using multi-dimensional particle swarm
      optimization (MD PSO). Multiple CNBCs are then used to form a CNBC ensemble (CNBC
      E), which aggregates epileptic seizure frames from the classification map of each
      CNBC in order to maximize the sensitivity rate. Finally, a morphological filter
      forms the final epileptic segments while filtering out the outliers in the form
      of classification noise. The proposed system is fully generic, which does not
      require any a priori information about the patient such as the list of relevant
      EEG channels. The results of the classification experiments, which are performed
      over the benchmark CHB-MIT scalp long-term EEG database show that the proposed
      system can achieve all the aforementioned objectives and exhibits a significantly
      superior performance compared to several other state-of-the-art methods. Using a
      limited training dataset that is formed by less than 2 min of seizure and 24 min
      of non-seizure data on the average taken from the early 25% section of the EEG
      record of each patient, the proposed system establishes an average sensitivity
      rate above 89% along with an average specificity rate above 93% over the test
      set.

PMID- 24566190
TI  - Polyethylene glycol-based hydrogels for controlled release of the antimicrobial
      subtilosin for prophylaxis of bacterial vaginosis.
AB  - Current treatment options for bacterial vaginosis (BV) have been shown to be
      inadequate at preventing recurrence and do not provide protection against
      associated infections, such as that with HIV. This study examines the feasibility
      of incorporating the antimicrobial peptide subtilosin within covalently cross
      linked polyethylene glycol (PEG)-based hydrogels for vaginal administration. The
      PEG-based hydrogels (4% and 6% [wt/vol]) provided a two-phase release of
      subtilosin, with an initial rapid release rate of 4.0 MUg/h (0 to 12 h) followed
      by a slow, sustained release rate of 0.26 MUg/h (12 to 120 h). The subtilosin
      containing hydrogels inhibited the growth of the major BV-associated pathogen
      Gardnerella vaginalis with a reduction of 8 log10 CFU/ml with hydrogels
      containing >=15 MUg entrapped subtilosin. In addition, the growth of four common
      species of vaginal lactobacilli was not significantly inhibited in the presence
      of the subtilosin-containing hydrogels. The above findings demonstrate the
      potential application of vaginal subtilosin-containing hydrogels for prophylaxis
      of BV. 

PMID- 24566196
TI  - Giant superior vena-cava aneurysm after Glenn surgery: a new complication of the
      Glenn procedure.

PMID- 24566195
TI  - Longitudinal trajectories of sensation seeking, risk taking propensity, and
      impulsivity across early to middle adolescence.
AB  - Adolescent substance use and abuse show associations with increases in
      disinhibitory constructs, including sensation seeking, risk taking propensity,
      and impulsivity. However, the longitudinal trajectories of these constructs from
      early to middle adolescence remain largely unknown. Thus, the current study
      examined these developmental trajectories in 277 adolescents (Mage=11.00 at Wave
      1), over five consecutive yearly waves. Controlling for age, Hierarchical Linear
      Modeling analyses showed that sensation seeking increased linearly, whereas risk
      taking propensity and impulsivity demonstrated curvilinear changes. Specifically,
      risk taking propensity increased in the first four waves of assessment but did
      not evidence changes at the last assessment wave. Impulsivity, on the other hand
      peaked at wave four before subsequently declining. A comparison between females
      and males and Black and White adolescents suggested that these groups'
      trajectories were similar. Black adolescents' sensation seeking trajectory
      differed from adolescents who belonged to the "Other" racial group (i.e.,
      adolescents who neither self-identified as Black or White). Generally, the study
      findings replicate and extend earlier work indicating that these risk factors
      increase across early adolescence and begin to level-off during middle
      adolescence. The importance of understanding the natural course of these core
      constructs is of great importance for directing future relevant prevention and
      intervention work. 

PMID- 24566197
TI  - Correlation between methyltetrahydrofolate reductase (MTHFR) polymorphisms and
      isolated patent ductus arteriosus in Taiwan.
AB  - BACKGROUND: Methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C gene
      polymorphisms are associated with the risk of patent ductus arteriosus (PDA)
      congenital heart defects. This study aimed to determine the association of these
      polymorphisms in patients with isolated PDA and in non-PDA patients group without
      congenital heart disease. METHODS: This retrospective case-controlled study was
      undertaken in 17 patients with isolated PDA and a control non-PDA group
      consisting of 34 subjects without congenital heart disease. MTHFR gene
      polymorphisms were analysed using polymerase chain reaction-restriction fragment
      length polymorphism (PCR-RFLP). In addition, the genotype distribution of the
      MTHFR gene was compared among different ethnicities using the HapMap database.
      RESULTS: In contrast to the MTHFR C677T polymorphism, differences in the MTHFR
      A1298C genotype were observed between the two groups (P=0.002); a greater
      proportion of the PDA patients had the MTHFR 1298CC and 1298AA genotypes as
      compared to the non-PDA control group. After merging the data obtained from the
      Taiwanese participants with that from the HapMap database, genetic diversity of
      the MTHFR 1298AA genotype was observed. CONCLUSIONS: Thus, the MTHFR A1298C
      polymorphism is associated with isolated PDA in Taiwan. Larger studies are
      necessary to evaluate the prognostic value of determining MTHFR polymorphism in
      PDA.

PMID- 24566198
TI  - Valve design and paravalvular aortic regurgitation: new insights from the French
      registry.

PMID- 24566199
TI  - Postprocedural aortic regurgitation in balloon-expandable and self-expandable
      transcatheter aortic valve replacement procedures: analysis of predictors and
      impact on long-term mortality: insights from the FRANCE2 Registry.
AB  - BACKGROUND: Significant postprocedural aortic regurgitation (AR) is observed in
      10% to 20% of cases after transcatheter aortic valve replacement (TAVR). The
      prognostic value and the predictors of such a complication in balloon-expandable
      (BE) and self-expandable (SE) TAVR remain unclear. METHODS AND RESULTS: TAVR was
      performed in 3195 consecutive patients at 34 hospitals. Postprocedural
      transthoracic echocardiography was performed in 2769 (92%) patients of the
      eligible population, and these patients constituted the study group. Median
      follow-up was 306 days (Q1-Q3=178-490). BE and SE devices were implanted in 67.6%
      (n=1872) and 32.4% (n=897). Delivery was femoral (75.3%) or nonfemoral (24.7%). A
      postprocedural AR>=grade 2 was observed in 15.8% and was more frequent in SE
      (21.5%) than in BE-TAVR (13.0%, P=0.0001). Extensive multivariable analysis
      confirmed that the use of a SE device was one of the most powerful independent
      predictors of postprocedural AR>=grade 2. For BE-TAVR, 8 independent predictors
      of postprocedural AR>=grade 2 were identified including femoral delivery
      (P=0.04), larger aortic annulus (P=0.0004), and smaller prosthesis diameter
      (P=0.0001). For SE-TAVR, 2 independent predictors were identified including
      femoral delivery(P=0.0001). Aortic annulus and prosthesis diameter were not
      predictors of postprocedural AR for SE-TAVR. A postprocedural AR>=grade 2, but
      not a postprocedural AR=grade 1, was a strong independent predictor of 1-year
      mortality for BE (hazard ratio=2.50; P=0.0001) and SE-TAVR (hazard ratio=2.11;
      P=0.0001). Although postprocedural AR>=grade 2 was well tolerated in patients
      with AR>=grade 2 at baseline (1-year mortality=7%), it was associated with a very
      high mortality in other subgroups: renal failure (43%), AR<grade 2 at baseline
      (31%), low transaortic gradient (35%), or nonfemoral delivery (45%). CONCLUSIONS:
      Postprocedural AR>=grade 2 was observed in 15.8% of successful TAVR and was the
      strongest independent predictor of 1-year mortality. The use of the SE device was
      a powerful independent predictor of postprocedural AR>=grade 2.

PMID- 24566200
TI  - Depression as a risk factor for poor prognosis among patients with acute coronary
      syndrome: systematic review and recommendations: a scientific statement from the
      American Heart Association.
AB  - BACKGROUND: Although prospective studies, systematic reviews, and meta-analyses
      have documented an association between depression and increased morbidity and
      mortality in a variety of cardiac populations, depression has not yet achieved
      formal recognition as a risk factor for poor prognosis in patients with acute
      coronary syndrome by the American Heart Association and other health
      organizations. The purpose of this scientific statement is to review available
      evidence and recommend whether depression should be elevated to the status of a
      risk factor for patients with acute coronary syndrome. METHODS AND RESULTS:
      Writing group members were approved by the American Heart Association's
      Scientific Statement and Manuscript Oversight Committees. A systematic literature
      review on depression and adverse medical outcomes after acute coronary syndrome
      was conducted that included all-cause mortality, cardiac mortality, and composite
      outcomes for mortality and nonfatal events. The review assessed the strength,
      consistency, independence, and generalizability of the published studies. A total
      of 53 individual studies (32 reported on associations with all-cause mortality,
      12 on cardiac mortality, and 22 on composite outcomes) and 4 meta-analyses met
      inclusion criteria. There was heterogeneity across studies in terms of the
      demographic composition of study samples, definition and measurement of
      depression, length of follow-up, and covariates included in the multivariable
      models. Despite limitations in some individual studies, our review identified
      generally consistent associations between depression and adverse outcomes.
      CONCLUSIONS: Despite the heterogeneity of published studies included in this
      review, the preponderance of evidence supports the recommendation that the
      American Heart Association should elevate depression to the status of a risk
      factor for adverse medical outcomes in patients with acute coronary syndrome.

PMID- 24566201
TI  - Effect of phosphomimetic mutations on the C-terminal sensitivity of glycine
      transporter GlyT1 to calpain.
AB  - Previously, we found that the C-terminus of the glycine transporter GlyT1 loses
      the most of its epitopes during pathological calcium increase in rodent
      synaptosomes but that the more internal epitopes are spared. We also found that
      epitope immunoreactivity likely decreases via both phosphorylation and calpain
      mediated proteolysis. Here we show that the predicted phosphomimetic mutation
      S605D fully blocks the adjacent (T602/T603) internal calpain cleavage in the
      mouse GlyT1b C-terminal fusion protein, but that the neutral S605A mutation does
      not. Consistent with this, the phophomimetic mutation, but not the neutral
      mutation, significantly protected the internal GlyT1 C-terminal antiGlyT1C603-626
      epitopes against calpain when introduced into tissue culture expressed GlyT1b.
      Because similar effects can be obtained using phosphatase inhibitors, it may be
      that phosphorylation of S605 protects the GlyT1 C-terminal sequences from calpain
      cleavage in vivo. 

PMID- 24566202
TI  - Serum levels of mannose-binding lectin in systemic sclerosis: a possible
      contribution to the initiation of skin sclerosis in the diffuse cutaneous
      subtype.

PMID- 24566204
TI  - Multi-capillary column-ion mobility spectrometer (MCC-IMS) breath analysis in
      ventilated rats: a model with the feasibility of long-term measurements.
AB  - Rats are commonly used in medical research as they enable a high grade of
      standardization. The exhalome of ventilated rats has not as yet been investigated
      using an ion mobility spectrometer coupled with a multi-capillary column (MCC
      IMS). As a first step, a rat model has to be established to measure potential
      biomarkers in the exhale with long-term settings, allowing constant and
      continuous analysis of exhaled air in time series. Therefore, eight animals were
      anaesthetized, prepared and ventilated for 1 h. A total of 73 peaks were directly
      detected with the IMS chromatogram. Thirty five of them were assigned to the
      ventilator system and 38 to the animals. Peak intensity varied within three
      measurements. The intensity of analytes of individual rats varied by a factor of
      up to 18. This new model will also enable continuous measurements of volatile
      organic compounds (VOCs) from rat's breath in long-term experiments. It is hoped
      that, in the future, variability and progression of VOCs can be monitored in
      different models of diseases using this set-up.

PMID- 24566205
TI  - More foundation trusts are missing targets, finds regulator.

PMID- 24566203
TI  - Treatment by asenapine for 5 weeks decreases weight and triglycerides levels of
      Wistar rats.

PMID- 24566206
TI  - Bilateral adrenal masses in a patient in remission from acute myelomonocytic
      leukemia.

PMID- 24566207
TI  - Female pelvic medicine and reconstructive surgery: the next decade.

PMID- 24566208
TI  - Neuroanatomy, neurophysiology, and dysfunction of the female lower urinary tract:
      a review.
AB  - The 2 major functions of the lower urinary tract are the storage and emptying of
      urine. These processes are controlled by complex neurophysiologic mechanisms and
      are subject to injury and disease. When there is disruption of the neurologic
      control centers, dysfunction of the lower urinary tract may occur. This is
      sometimes referred to as the "neurogenic bladder." The manifestation of
      dysfunction depends on the level of injury and severity of disruption. Patients
      with lesions above the spinal cord often have detrusor overactivity with no
      disruption in detrusor-sphincter coordination. Patients with well-defined
      suprasacral spinal cord injuries usually present with intact reflex detrusor
      activity but have detrusor sphincter dyssynergia, whereas injuries to or below
      the sacral spinal cord usually lead to persistent detrusor areflexia. A complete
      gynecologic, urologic, and neurologic examination should be performed when
      evaluating patients with neurologic lower urinary tract dysfunction. In addition,
      urodynamic studies and neurophysiologic testing can be used in certain
      circumstances to help establish diagnosis or to achieve better understanding of a
      patient's vesicourethral functioning. In the management of neurogenic lower
      urinary tract dysfunction, the primary goal is improvement of a patient's quality
      of life. Second to this is the prevention of chronic damage to the bladder and
      kidneys, which can lead to worsening impairment and symptoms. Treatment is often
      multifactorial, including behavioral modifications, bladder training programs,
      and pharmacotherapy. Surgical procedures are often a last resort option for
      management. An understanding of the basic neurophysiologic mechanisms of the
      lower urinary tract can guide providers in their evaluation and treatment of
      patients who present with lower urinary tract disorders. As neurologic diseases
      progress, voiding function often changes or worsens, necessitating a good
      understanding of the underlying physiology in question. 

PMID- 24566209
TI  - Training community gynecologists to perform intraoperative cystoscopy: a
      competency-based training experience.
AB  - OBJECTIVE: This study aimed to pilot a cystoscopy training program for community
      gynecologists that is validated by posttraining examination. METHODS: Twenty
      eight gynecologists were trained to perform cystoscopy using a competency-based
      training approach. Baseline information included years in practice and number of
      incontinence procedures and/or cystoscopies performed per month. Three 5-hour
      workshops were administered that included applied practice. After learners
      individually trained until they felt comfortable with their skills on a model,
      they were individually tested on a cadaver. Performance was evaluated with 2
      instruments, namely, a task-specific checklist and a global rating scale based on
      the objective structured assessment of technical skill model. Failure was defined
      as inability to independently complete elements of the task-specific checklist
      for cystoscopic examination. Likert-type self-report scales were used during
      pretesting and posttesting, assessing confidence to perform component tasks for
      diagnostic cystoscopy. RESULTS: Twenty-four of 28 trainees successfully performed
      a systematic cadaveric bladder examination during the primary posttest. After
      debriefing, the 4 trainees who initially failed successfully performed cystoscopy
      during a second trial. Median age was 51 years and median time in practice was
      19.5 years. All participants reported high confidence in identifying ureteral
      injury at the course's conclusion. CONCLUSIONS: A task-specific training program
      can successfully improve the confidence and skill of community gynecologists to
      perform intraoperative diagnostic cystoscopy. Professionals may not be able to
      define when they have received enough instruction in terms of hands-on training
      with models, before acquisition of technical skills. Formal evaluation of
      technical skills is recommended after training to ensure competence.

PMID- 24566210
TI  - Robotic sacrocolpopexy performance and cumulative summation analysis.
AB  - OBJECTIVES: This study aimed to apply Cumulative Summation (CUSUM) analysis as a
      tool to monitor robotic sacrocolpopexy (RSCP) proficiency over time. METHODS: A
      retrospective analysis of all women who underwent RSCP between September of 2008
      and December of 2011 at the University of North Carolina at Chapel Hill. The
      performance for 2 attending surgeons was analyzed sequentially over time.
      Intraoperative complications such as genitourinary or gastrointestinal tract
      injury, conversion to laparotomy, pulmonary embolus, hemorrhage, and blood
      transfusion, were identified by International Classification of Diseases, Ninth
      Revision and Current Procedural Terminology codes. A successful outcome was
      defined as no intraoperative complications. The target value of success was set
      at less than 10% complications. CUSUM analysis was then sequentially applied to
      all RSCP cases for 2 attending surgeons. RESULTS: Over 27 months, 169 RSCPs were
      performed. The first surgeon performed 107 RSCPs and the second surgeon performed
      62 RSCPs with 8 (7.4%) and 3 (4.9%) intraoperative complications, respectively.
      Total complications included 7 (4.1%) cystotomies, 2 (1.2%) vaginal lacerations,
      1 (0.6%) blood transfusion, and 1 (0.6%) bowel perforation. A CUSUM graph was
      created for each surgeon. CONCLUSIONS: CUSUM analysis was successfully applied to
      monitor RSCP proficiency. Such testing of individual successive procedural
      outcomes with CUSUM may offer an objective tool to aid in physician self
      assessment.

PMID- 24566211
TI  - Prospective cohort study of bowel function after robotic sacrocolpopexy.
AB  - OBJECTIVE: This study aimed to determine bowel function changes 12 months after
      robotic sacrocolpopexy. METHODS: We performed a single-center prospective cohort
      study evaluating bowel function 12 months after robotic sacrocolpopexy between
      2007 and 2011. Bowel function symptoms were measured by the Colorectal-Anal
      Distress Inventory, Short Form 8 (CRADI-8). Specific impacts on quality of life
      with regard to bowel function were evaluated using the Colorectal-Anal Impact
      Questionnaire, Short Form 7 (CRAIQ-7). "Splinting to defecate" was defined as any
      positive response to question 4 of the Pelvic Floor Distress Inventory-20 which
      reads, "do you ever have to push on the vagina or around the rectum to have or
      complete a bowel movement?." Lastly, patients were grouped according to
      perineorrhaphy versus no perineorrhaphy and bowel function scores were examined.
      RESULTS: Of 423 consecutive patients who underwent robotic sacrocolpopexy at our
      institution, 393 (93%) completed a 12-month follow-up. Mean CRADI-8 scores at
      baseline and 12 months were 21.1 (20) and 7.3 (11), respectively (P < 0.0001).
      Mean CRAIQ-7 scores at baseline and 12 months were 11.1 (20) and 2.4 (9),
      respectively (P < 0.0001). Preoperatively, 152 patients reported a need to splint
      the vagina or perineum to complete a bowel movement. At 12 months, 70% reported
      complete resolution of "splinting." Con comitant perineorrhaphy was performed on
      87 patients and there were no differences in 12-month CRADI-8 or CRAIQ-7 scores
      between groups. CONCLUSIONS: Robotic sacrocolpopexy was associated with
      significant improvements in bowel function as measured by CRADI-8 as well as
      improvements in impact on quality of life as measured by CRAIQ-7.

PMID- 24566212
TI  - Is postoperative bowel function related to posterior compartment prolapse repair?
AB  - OBJECTIVES: This study aimed to assess how posterior repair (PR) affects change
      in bowel function in women undergoing anterior/apical surgery for prolapse.
      METHODS: We performed a retrospective cohort study of women undergoing prolapse
      surgery. Our 2 cohorts were women who underwent anterior/apical prolapse surgery
      either with or without a PR. All women completed the short form of the Colorectal
      Anal Distress Inventory (CRADI-8) preoperatively and 6 weeks postoperatively. We
      compared change in CRADI-8 scores between those who received PR versus those who
      did not. RESULTS: Among 238 women who underwent anterior/apical prolapse surgery,
      61 (26%) underwent PR, whereas 177 (74%) did not undergo PR. There were no
      significant differences in mean CRADI-8 scores at baseline or postoperatively,
      and scores improved significantly in both groups [baseline scores 23.2 (20.2) for
      PR vs 18.2 (19.3) for no PR, P = 0.12; postoperative scores 5.0 (10.5) for PR vs
      8.4 (15.4) for no PR, P = 0.08]. For our primary outcome, we identified a
      significantly larger margin of symptom improvement in those who underwent PR
      compared to those who did not [mean CRADI-8 change scores 18.2 (20.1) for PR vs
      9.9 (18.6) for no PR, P < 0.01]. In a linear regression model assessing
      postoperative CRADI-8 scores, women who underwent PR scored 4.9 points lower on
      the postoperative CRADI-8, suggesting more improvement in bowel-related symptoms,
      compared to those who did not undergo PR (95% confidence interval, 1.0, 8.8, P =
      0.02). CONCLUSIONS: Women undergoing surgery for anterior/apical prolapse
      demonstrated significant improvements in bowel symptoms after surgery. Those
      receiving concomitant PR had a significantly greater margin of improvement.

PMID- 24566213
TI  - The impact of pessary use on bowel symptoms: one-year outcomes.
AB  - OBJECTIVES: The literature states that patients with pelvic organ prolapse have a
      higher prevalence of bothersome bowel symptoms and that surgical correction of
      prolapse may improve bowel function. There is limited knowledge regarding the
      impact of pessary use on bowel function in patients with prolapse. The aim of
      this study was to evaluate if there is a change in bowel symptoms in patients
      with prolapse treated with a vaginal pessary. METHODS: Women who presented for
      pessary insertion completed the validated questionnaires on the bowel symptom
      severity and on the effect of bowel symptoms on the quality of life at baseline
      and again at 12 months of continuous pessary use. Inferential statistics
      comprised Student t test for evaluating differences in continuous Gaussian data
      between groups and paired t tests were used to evaluate differences among
      subjects between the baseline and 12 months of use. RESULTS: One hundred four
      women participated in the original study, and 43 had complete data for analysis.
      Women who completed 12 months of pessary use reported significant improvements in
      both bowel-related symptoms and bowel-related quality of life (95% confidence
      interval of the difference 1.6-11.4 and 2.0-14.0, respectively). Patients who
      completed the 12-month follow-up were significantly older and more likely to have
      stage 3 or 4 prolapse than noncompleters, but there were no differences in body
      mass index, race, history of prior prolapse surgery, or menopause status.
      CONCLUSIONS: In women with prolapse, the use of a pessary is associated with a
      decrease in complaints related to bowel symptoms.

PMID- 24566215
TI  - Goals, symptoms, signs, and treatments among women with pelvic floor disorders.
AB  - OBJECTIVE: This study aimed to identify associations between patient-centered
      goals and pelvic floor measures and treatment choice. METHODS: A retrospective
      study of women seen for a pelvic floor disorder by a single surgeon in a
      specialty clinic from January 2008 to December 2009 was done. Goals were
      categorized as information-seeking, improving across any of 6 pelvic floor
      symptom categories, and "other." Pelvic floor symptom burden was determined using
      validated surveys. Health-related quality of life (HRQoL) and vaginal Pelvic
      Organ Prolapse Quantification points were assessed. Correlations of goals with
      symptom burden, HRQoL, and anatomic severity and surgical versus nonoperative
      care were determined. RESULTS: Ninety patients met inclusion criteria. The mean
      (SD) age was 56 (14) years, with 67% younger than 65 years; 23.3% of the patients
      reported a surgery treatment preference; 30.7% had at least 1 Pelvic Organ
      Prolapse Quantification point greater than or equal to 1 cm. A single goal was
      reported by 18% of patients with 28%, 37%, 14%, and 3.3% reporting 2, 3, 4, or 5
      goals. Goals reflected symptom burden for bowel and bladder complaints, whereas a
      cosmetic goal seems to reflect both prolapse symptoms and impact as well as
      measurably altered anatomy. Goals related to sexual function reflected overall
      mental HRQoL but not symptoms or anatomy. Women with an activity-based goal
      preferred surgery but the low number of patients who chose surgery did allow
      statistical significance. CONCLUSIONS: There are not always correlations between
      a patient's therapeutic goals and subjective and objective assessments of the
      pelvic floor or treatment choice.

PMID- 24566214
TI  - Characterization of pain after inside-out transobturator midurethral sling.
AB  - OBJECTIVES: This study aimed to evaluate the prevalence, severity, duration, and
      location of pain after transobturator midurethral sling. METHODS: We evaluated
      patients who underwent inside-out transobturator sling from March 2011 through
      February 2013. Presence of pelvic girdle pain, its severity, and location were
      documented preoperatively and at 2- and 6-week postoperative visits. Pain
      severity was measured on a scale of 1 to 10, with 10 being the "worst imaginable"
      pain. RESULTS: Of the 130 women analyzed, the median age was 50.0 years
      (interquartile range, 44.0-62.0). Thirty-nine percent of women reported
      preoperative pain, mostly mild with a median score of 1.0 (1.0-5.0). The most
      common sites of postoperative-onset pain were the lateral leg, medial leg, groin,
      and low back. Women reporting preoperative pain were not more likely to report
      postoperative-onset pain than women without preoperative pain (P = 0.42). Twelve
      percent of women at 2 weeks and 0.8% at 6 weeks reported severe postoperative
      onset pain. Women reporting postoperative-onset pain were equally likely to be
      satisfied with the procedure as those without pain at 2 (P = 0.76) and 6 (P =
      0.74) weeks. CONCLUSIONS: Women undergoing transobturator sling commonly report
      preoperative pain. An expected postoperative increase in pain generally resolved
      by the sixth postoperative week. The lateral leg was the most common site of
      pain. Postoperative-onset pain was not associated with decreased patient
      satisfaction.

PMID- 24566216
TI  - Lung collapse secondary to mucus plug in a gynecologic patient after
      reconstructive pelvic surgery.
AB  - This is the case of a 45-year-old woman with a history of asthma and smoking who
      developed complete left lung and right upper lobe collapse secondary to mucus
      plugs that developed immediately postoperatively after an uncomplicated
      reconstructive pelvic surgery. This rare intraoperative complication was
      successfully treated in the recovery room with bedside fiber-optic bronchoscopy.
      This resulted in complete resolution of her pulmonary findings within 24 hours of
      bronchoscopy. 

PMID- 24566217
TI  - Unanticipated uterine pathologic finding after morcellation during robotic
      assisted supracervical hysterectomy and cervicosacropexy for uterine prolapse.
AB  - BACKGROUND: Identification of occult malignancy after intra-abdominal
      morcellation at the time of robotic-assisted supracervical hysterectomy and
      cervicosacropexy for uterine prolapse may lead to challenging postoperative
      management and leads one to question the need for preoperative evaluation. CASES:
      We present 2 cases of occult endometrial carcinoma after robotic-assisted
      supracervical hysterectomy and cervicosacropexy with intra-abdominal uterine
      morcellation from January 2008 to December 2010. A total of 63 patients underwent
      the stated surgical procedure with 2 patients (3.17%) found to have abnormal
      uterine pathologic finding with International Federation of Gynecology and
      Obstetrics grade 1 endometrial adenocarcinoma. Both cases occurred in
      asymptomatic postmenopausal patients without risk factors for endometrial cancer,
      including no history of postmenopausal bleeding or hormone replacement therapy.
      Owing to intraoperative uterine morcellation and cervical retention, appropriate
      postoperative management was controversial and problematic. Each patient was
      referred to gynecologic oncology. To date, both patients are without evidence of
      residual disease. CONCLUSION: Owing to the risk of occult uterine pathologic
      finding and complicated postoperative management, preoperative endometrial
      assessment should be considered on all postmenopausal patients undergoing intra
      abdominal uterine morcellation, regardless of risk factors.

PMID- 24566218
TI  - Vaginal trachelectomy following laparoscopic supracervical hysterectomy and
      sacrocervicopexy.
AB  - BACKGROUND: Current evidence supports cervical preservation at the time of
      abdominal prolapse repair using synthetic mesh to minimize vaginal mesh
      extrusion. This report aims to describe management of benign cervical disease
      following laparoscopic sacrocervicopexy including successful trachelectomy
      performed vaginally. CASE: A 70-year-old sexually active woman presented with
      symptomatic pelvic organ prolapse and stress urinary incontinence. Her
      Papanicolaou smears over several years were unremarkable, and she had a benign
      endocervical polyp removed in the office 3 months before surgery. She underwent
      an uncomplicated robotic-assisted laparoscopic supracervical hysterectomy and
      sacrocervicopexy. She presented 8 months after surgery with persistent vaginal
      spotting after intercourse and was found to have a recurrent endocervical polyp.
      Ultimately, she underwent uncomplicated trachelectomy performed vaginally with
      resolution of her symptoms. CONCLUSIONS: Retention of the cervix at the time of
      mesh-augmented abdominal prolapse repairs introduces a unique set of evaluation
      and management considerations for benign cervical disease. Trachelectomy
      performed vaginally was successful and uncomplicated in this case.

PMID- 24566219
TI  - Minimally invasive management of retropubic bleeding and hematoma evacuation
      after a TVT Secur or mini-sling procedure.
AB  - BACKGROUND: Retropubic hematomas may complicate up to 4.1% of tension-free
      vaginal tape (TVT) procedures in the surgical treatment of stress urinary
      incontinence. Symptomatic or expanding hematomas often require intervention,
      usually accomplished through an abdominal incision. CASE: A 43-year-old woman
      underwent transvaginal management of venous bleeding and evacuation of a 1500-mL
      retropubic hematoma after a TVT Secur or "mini-sling" procedure. CONCLUSIONS:
      Significant bleeding can complicate even the least invasive surgical approach to
      treat stress urinary incontinence. Transvaginal evacuation of a symptomatic
      retropubic hematoma with instillation of a hemostatic agent may be a safe
      alternative to laparotomy in a hemodynamically stable patient.

PMID- 24566220
TI  - The use of a Google search in the diagnosis of a rare condition.
AB  - BACKGROUND: This study aims to describe the use of the Internet in aiding the
      diagnosis of a rare lower urinary tract finding in a primiparous woman. METHODS:
      A case of bladder schistosomiasis was reviewed. RESULTS: After the referral from
      the obstetrics service with a bladder lesion noted on dating ultrasound, an
      asymptomatic primipara with 9 weeks of gestational age presented for cystoscopy.
      A polypoid lesion was noted, and suspected diagnosis of schistosomiasis was made
      using a Google image search. Urine cytologic evaluation confirmed the diagnosis,
      and the patient was treated without need for further invasive testing or bladder
      biopsy. CONCLUSIONS: The usefulness of Internet searches and other electronic
      resources should be appreciated in the diagnosis of rare conditions.

PMID- 24566222
TI  - Halitosis management by the general dental practitioner--results of an
      international consensus workshop.
AB  - Clinical investigations on patients suffering from halitosis clearly reveal that
      in the vast majority of cases the source for an offensive breath odor can be
      found within the oral cavity (90%). Based on these studies, the main sources for
      intra-oral halitosis where tongue coating, gingivitis/periodontitis or a
      combination of the two. Thus, it is perfectly logical that general dental
      practitioners (GDPs) should be able to manage intra-oral halitosis under the
      conditions found in a normal dental practice. However, GDPs who are interested in
      diagnosing and treating halitosis are challenged to incorporate scientifically
      based strategies for use in their clinics. Therefore, the present paper
      summarizes the results of a consensus workshop of international authorities held
      with the aim to reach a consensus on general guidelines on how to assess and
      diagnose patients' breath odor concerns and general guidelines on regimens for
      the treatment of halitosis. 

PMID- 24566223
TI  - Human coronavirus NL63 replication is cyclophilin A-dependent and inhibited by
      non-immunosuppressive cyclosporine A-derivatives including Alisporivir.
AB  - Until recently, there were no effective drugs available blocking coronavirus
      (CoV) infection in humans and animals. We have shown before that CsA and FK506
      inhibit coronavirus replication (Carbajo-Lozoya, J., Muller, M.A., Kallies, S.,
      Thiel, V., Drosten, C., von Brunn, A. Replication of human coronaviruses SARS
      CoV, HCoV-NL63 and HCoV-229E is inhibited by the drug FK506. Virus Res. 2012;
      Pfefferle, S., Schopf, J., Kogl, M., Friedel, C., Muller, M.A., Stellberger, T.,
      von Dall'Armi, E., Herzog, P., Kallies, S., Niemeyer, D., Ditt, V., Kuri, T.,
      Zust, R., Schwarz, F., Zimmer, R., Steffen, I., Weber, F., Thiel, V., Herrler,
      G., Thiel, H.-J., Schwegmann-Webetaels, C., Pohlmann, S., Haas, J., Drosten, C.
      and von Brunn, A. The SARS-Coronavirus-host interactome: identification of
      cyclophilins as target for pan-Coronavirus inhibitors. PLoS Pathog., 2011). Here
      we demonstrate that CsD Alisporivir, NIM811 as well as novel non
      immunosuppressive derivatives of CsA and FK506 strongly inhibit the growth of
      human coronavirus HCoV-NL63 at low micromolar, non-cytotoxic concentrations in
      cell culture. We show by qPCR analysis that virus replication is diminished up to
      four orders of magnitude to background levels. Knockdown of the cellular
      Cyclophilin A (CypA/PPIA) gene in Caco-2 cells prevents replication of HCoV-NL63,
      suggesting that CypA is required for virus replication. Collectively, our results
      uncover Cyclophilin A as a host target for CoV infection and provide new
      strategies for urgently needed therapeutic approaches. 

PMID- 24566224
TI  - Institute of Medicine's Global Forum on Innovation in Health Professional
      Education.

PMID- 24566221
TI  - beta-Adrenergic receptor-mediated transactivation of epidermal growth factor
      receptor decreases cardiomyocyte apoptosis through differential subcellular
      activation of ERK1/2 and Akt.
AB  - beta-Adrenergic receptor (betaAR)-mediated transactivation of epidermal growth
      factor receptor (EGFR) has been shown to relay pro-survival effects via unknown
      mechanisms. We hypothesized that acute betaAR-mediated EGFR transactivation in
      the heart promotes differential subcellular activation of ERK1/2 and Akt,
      promoting cell survival through modulation of apoptosis. C57BL/6 mice underwent
      acute i.p. injection with isoproterenol (ISO)+/-AG 1478 (EGFR antagonist) to
      assess the impact of betaAR-mediated EGFR transactivation on the phosphorylation
      of ERK1/2 (P-ERK1/2) and Akt (P-Akt) in distinct cardiac subcellular fractions.
      Increased P-ERK1/2 and P-Akt were observed in cytosolic, plasma membrane and
      nuclear fractions following ISO stimulation. Whereas the P-ERK1/2 response was
      EGFR-sensitive in all fractions, the P-Akt response was EGFR-sensitive only in
      the plasma membrane and nucleus, results confirmed in primary rat neonatal
      cardiomyocytes (RNCM). betaAR-mediated EGFR-transactivation also decreased
      apoptosis in serum-depleted RNCM, as measured via TUNEL as well as caspase 3
      activity/cleavage, which were sensitive to the inhibition of either ERK1/2
      (PD184352) or Akt (LY-294002) signaling. Caspase 3 activity/cleavage was also
      sensitive to the inhibition of transcription, which, with an increase in nuclear
      P-ERK1/2 and P-Akt in response to ISO, suggested that betaAR-mediated EGFR
      transactivation may regulate apoptotic gene transcription. An Apoptosis PCR Array
      identified tnfsf10 (TRAIL) to be altered by ISO in an EGFR-sensitive manner,
      results confirmed via RT-PCR and ELISA measurement of both membrane-bound and
      soluble cardiomyocyte TRAIL levels. betaAR-mediated EGFR transactivation induces
      differential subcellular activation of ERK1/2 and Akt leading to increased cell
      survival through the modulation of caspase 3 activity and apoptotic gene
      expression in cardiomyocytes. 

PMID- 24566226
TI  - Bilateral jugular paragangliomas: a rare cause of raised intracranial pressure.

PMID- 24566225
TI  - Summary of evidence-based guideline update: prevention of stroke in nonvalvular
      atrial fibrillation: report of the Guideline Development Subcommittee of the
      American Academy of Neurology.
AB  - OBJECTIVE: To update the 1998 American Academy of Neurology practice parameter on
      stroke prevention in nonvalvular atrial fibrillation (NVAF). How often do various
      technologies identify previously undetected NVAF? Which therapies reduce ischemic
      stroke risk with the least risk of hemorrhage, including intracranial hemorrhage?
      The complete guideline on which this summary is based is available as an online
      data supplement to this article. METHODS: Systematic literature review; modified
      Delphi process recommendation formulation. MAJOR CONCLUSIONS: In patients with
      recent cryptogenic stroke, cardiac rhythm monitoring probably detects occult
      NVAF. In patients with NVAF, dabigatran, rivaroxaban, and apixaban are probably
      at least as effective as warfarin in preventing stroke and have a lower risk of
      intracranial hemorrhage. Triflusal plus acenocoumarol is likely more effective
      than acenocoumarol alone in reducing stroke risk. Clopidogrel plus aspirin is
      probably less effective than warfarin in preventing stroke and has a lower risk
      of intracranial bleeding. Clopidogrel plus aspirin as compared with aspirin alone
      probably reduces stroke risk but increases the risk of major hemorrhage. Apixaban
      is likely more effective than aspirin for decreasing stroke risk and has a
      bleeding risk similar to that of aspirin. MAJOR RECOMMENDATIONS: Clinicians might
      obtain outpatient cardiac rhythm studies in patients with cryptogenic stroke to
      identify patients with occult NVAF (Level C) and should routinely offer
      anticoagulation to patients with NVAF and a history of TIA/stroke (Level B).
      Specific patient considerations will inform anticoagulant selection in patients
      with NVAF judged to need anticoagulation.

PMID- 24566227
TI  - When is a global health program global?

PMID- 24566228
TI  - Education research: changing practice: residents' adoption of the atraumatic
      lumbar puncture needle.

PMID- 24566229
TI  - Mystery case: eyelid myoclonia with absences in an adult patient.

PMID- 24566230
TI  - Clinical reasoning: a 49-year-old man with fever and proximal weakness of his
      arms.

PMID- 24566231
TI  - Teaching video neuroimages: orofacial dyskinesia and oral ulceration due to
      involuntary biting in neuroacanthocytosis.

PMID- 24566232
TI  - Taking epilepsy medications consistently: why it makes a difference.

PMID- 24566234
TI  - Is sleep-disordered breathing associated with miscarriages? An emerging
      hypothesis.
AB  - Sleep-disordered breathing (SDB) is a common disorder that has numerous medical
      consequences including cardiovascular morbidity. The clinical presentation in
      women is frequently vague, leading to its under-recognition in this population.
      Sleep is known to influence several female hormonal cycles including estrogen,
      progesterone, prolactin, luteinizing hormone (LH), and follicle stimulating
      hormone (FSH); consequently, sleep disruption may have adverse effects on female
      health including pregnancy. Miscarriage, defined as the loss of a pregnancy in
      the first trimester, occurs in one in four pregnancies; in up to half of cases,
      the cause may be unknown. Risk factors for miscarriage include increased age,
      increased weight, and a history of polycystic ovarian syndrome, all of which are
      also risk factors for SDB. Since SDB is frequently accompanied by sleep
      fragmentation and intermittent hypoxemia, we speculate that these factors may
      contribute to miscarriage risk. If this is the case, then treatment of SDB may be
      a possible intervention for subsequent pregnancies. 

PMID- 24566235
TI  - Meningismus in children with chronic headache is most likely due to streptococcal
      infection.
AB  - We previously found that 97% of children diagnosed with chronic tension-type
      headaches had meningismus. In the present study, we investigate the relationship
      between streptococcal infection and meningismus in children suffering from
      chronic headaches. Six hundred and forty children suffering from idiopathic
      chronic headaches were examined by a neurologist in an outpatient setting.
      Antistreptolysin titer (ASOT) was determined from blood samples taken from all
      the children. Meningismus was diagnosed in 337 patients. Patients were divided
      into two groups: 337 children (Group 1) with meningismus with an increased ASOT
      (200-1790 IU/ml) in 264 children (78%), and 303 children (Group 2) without
      meningismus with an increased ASOT (200-1030 IU/ml) in 117 children (39%). We
      report herein that a majority of children with headaches associated with
      meningismus, had evidence of a streptococcal infection when compared to a non
      meningismus group. We postulate that streptococcal infection may play an
      important role in the etiology of meningismus-positive chronic headaches in
      children.

PMID- 24566233
TI  - Utilization rates of implantable cardioverter-defibrillators for primary
      prevention of sudden cardiac death: a 2012 calculation for a midwestern health
      referral region.
AB  - BACKGROUND: Utilization rates (URs) for implantable cardioverter-defibrillators
      (ICDs) for primary prevention of sudden cardiac death (PPSCD) are lacking in the
      community. OBJECTIVE: The purpose of this study was to establish the ICD UR in
      central Indiana. METHODS: A query run on 2 hospitals in a health information
      exchange database in Indianapolis identified patients between 2011 and 2012 with
      left ventricular ejection fraction (EF) <=0.35. ICD eligibility and utilization
      were determined from chart review. RESULTS: We identified 1863 patients with at
      least 1 low EF study. Two cohorts were analyzed: 1672 patients without and 191
      patients with International Classification of Diseases, Ninth Revision, Clinical
      Modification procedure code 37.94 for ICD placement. We manually reviewed a
      stratified (by hospital) random sample of 300 patients from the no-ICD procedure
      code cohort and found that 48 (16%) had no ICD but had class I indications for
      ICD. Eight of 300 (2.7%) actually had ICD implantation for PPSCD. Review of all
      191 patients in the ICD procedure code cohort identified 70 with ICD implantation
      for PPSCD. The ICD UR (ratio between patients with ICD for PPSCD and all with
      indication) was 38% overall (95% confidence interval [CI] 28%-49%). URs were 48%
      for males (95% CI 34%-61%), 21% for females (95% CI 16%-26%, P = .0002 vs males),
      40% for whites (95% CI 27%-53%), and 37% for blacks (95% CI 28%-46%, P = .66 vs
      whites). CONCLUSION: ICD UR is 38% among patients meeting class I indications,
      suggesting further opportunities for improving guideline compliance. This study
      also illustrates limitations in calculating ICD UR using large electronic
      repositories without hands-on chart review.

PMID- 24566236
TI  - Stress-induced gastrointestinal motility is responsible for epileptic
      susceptibility.
AB  - In order to explain observations linking epileptic EEG patterns (3 Hz spike wave
      complexes and beta-gamma activity of 25-40 Hz) and the involuntary slow wave of
      the gut (3 c/min) and colonic contractile electrical complexes (25-40 c/min), the
      physiological and pathological electrographic patterns recorded from different
      anatomical structures were compared. The similarities in shape and pattern
      provided the basis to hypothesise that these waves exist as a continuum
      associated with different cell types and that stress induces high-force
      involuntary tonic contractions and resistance to the segmental rhythmic
      contractions of the gut's circular muscles. As a consequence, electrographic
      patterns with a waveform of 3 c/min and 25-40 c/min are organised in the
      periphery and transmitted to the central nervous system via visceral afferents
      with the same shape. The electrical interactions between the adjacent neurons of
      the enteric network, as well as between the interconnected gut/brain neuronal
      circuits, facilitate synchronisation of neuronal activity by the frequencies of
      the stress-induced patterns. In this way, the peripherally organised
      electrographic patterns actively participate in creating epileptic susceptibility
      with expressed gut symptoms.

PMID- 24566237
TI  - The European Standard Series and its additions: are they of any use in 2013?
AB  - This study has two purposes:--to know whether the European standard series is
      still the key reference when it comes to contact dermatitis, i.e., are its
      components still the most frequently involved allergens in contact dermatitis
      nowadays?--to assess the results of the European standard series among French and
      Belgian dermatologists/allergists as, so far, most of them have failed to provide
      statistical data within the European community of allergists/dermatologists. 18
      participants from 2 dermatology and allergy centres in Belgium and 11 centres in
      France collected their results from 3,073 patients tested in 2011. They assessed
      the relevance of some tests as well as that of the standard series and additional
      series to establish an etiological diagnosis of contact dermatitis. These
      results, together with the history of the European standard series, have shown
      that some allergens are obsolete and that others should be included in a new
      standard series for which we are making a few suggestions.

PMID- 24566238
TI  - Screening for metabolic syndrome in older patients with severe mental illness.
AB  - OBJECTIVE: To evaluate metabolic screening of elderly patients with severe mental
      illness (SMI) in terms of newly detected metabolic abnormalities. METHODS:
      Prospective evaluation of the metabolic screening outcome data of 100 consecutive
      elderly outpatients with SMI, all with universal access to health services. We
      gathered data on previous diagnoses of hypertension, diabetes, and dyslipidemia
      and assessed metabolic syndrome parameters. The findings were compared with those
      from a group of 124 healthy elderly. RESULTS: In our patients with SMI (mean age:
      69 years; 52% bipolar disorder, 48% schizophrenia), the frequency of metabolic
      syndrome was not higher compared with the healthy elderly. However, in 51% of the
      SMI sample, metabolic screening detected at least one metabolic abnormality in a
      patient with no prior history for that specific parameter. CONCLUSION:
      Implementing routine screening for metabolic syndrome in elderly patients with
      SMI may reveal substantial rates of previously undetected metabolic
      abnormalities.

PMID- 24566239
TI  - Prevalence and correlates of renal disease in older lithium users: a population
      based study.
AB  - OBJECTIVE: Lithium is an important treatment for mood disorders, but concern
      about its association with renal disease has contributed to its limited use,
      particularly in older adults. Because high-quality evidence examining renal
      disease in this population is lacking, this study aims to quantify the prevalence
      and identify clinical correlates of renal disease in geriatric lithium users.
      METHODS: In a population-based cross-sectional study on 2,480 lithium users aged
      70 or more years, the authors searched the provincial administrative health data
      from Ontario, Canada between April 1, 2005 and March 31, 2011. Prevalence of
      chronic kidney disease (CKD), acute kidney injury (AKI), and nephrogenic diabetes
      insipidus (NDI) was measured using International Classification of Diseases,
      Tenth Revision codes. Logistic regression analyses were used to identify
      independent correlates of renal disease. RESULTS: The 6-year prevalence rates of
      CKD, AKI, and NDI were 13.9%, 1.3%, and 3.0%, respectively. Hypertension (odds
      ratio [OR]: 2.05; 95% confidence interval [CI]: 1.50-2.79), diabetes mellitus
      (OR: 1.86; 95% CI: 1.45-2.38), ischemic heart disease (OR: 1.65; 95% CI: 1.24
      2.20), NDI (OR: 2.54; 95% CI: 1.47-4.40), AKI (OR: 11.7; 95% CI: 5.26-26.1),
      lithium use for more than 2 years (OR: 1.71; 95% CI: 1.05-2.81), loop diuretic
      use (OR: 1.74; 95% CI: 1.26-2.41), hydrochlorothiazide use (OR: 1.48; 95% CI:
      1.07-2.05), and atypical antipsychotic use (OR: 1.49; 95% CI: 1.17-1.89) were all
      independently associated with CKD. CONCLUSION: Older lithium users have high
      rates of CKD. Lithium use duration was independently associated with CKD.
      Longitudinal studies including individuals without lithium exposure will be
      necessary to confirm whether lithium is indeed a risk factor for CKD in older
      adults.

PMID- 24566240
TI  - Daily stressors and adult day service use by family caregivers: effects on
      depressive symptoms, positive mood, and dehydroepiandrosterone-sulfate.
AB  - OBJECTIVE: This study examines effects of daily use of adult day service (ADS)
      programs by caregivers of individuals with dementia (IWD) on a salivary biomarker
      of stress reactivity, dehydroepiandrosterone-sulfate (DHEA-S), and whether these
      effects on DHEA-S are associated with daily variability in positive mood and
      depressive symptoms. METHODS: We used a daily diary design of 8 consecutive days
      with alternation of intervention (ADS) and nonintervention days to evaluate
      within- and between-person effects of the intervention. Family caregivers (N =
      151) of IWD who were using ADS were interviewed daily by telephone at home.
      Saliva samples were collected from caregivers five times a day for 8 consecutive
      days and were assayed for DHEA-S. Daily telephone interviews assessed daily
      stressors and mood. RESULTS: DHEA-S levels were significantly higher on days
      after ADS use. Daily DHEA-S levels covaried significantly with daily positive
      mood but not with depressive symptoms. CONCLUSION: These results demonstrate an
      association of ADS use by family caregivers and higher DHEA-S levels on the next
      day. Prior research has found that higher DHEA-S levels are protective against
      the physiologic damaging effects of stressor exposure and may reduce risks of
      illness. Regular use of ADS may help reduce depletion of DHEA-S and allow the
      body to mount a protective and restorative response to the physiologic demands of
      caregiving. To our knowledge, this is the first study to examine DHEA-S levels
      across the day in connection with an intervention that affected daily exposure to
      stressors.

PMID- 24566241
TI  - Expression, stabilization and purification of membrane proteins via diverse
      protein synthesis systems and detergents involving cell-free associated with self
      assembly peptide surfactants.
AB  - G-protein coupled receptors (GPCRs) are involved in regulating most of
      physiological actions and metabolism in the bodies, which have become most
      frequently addressed therapeutic targets for various disorders and diseases.
      Purified GPCR-based drug discoveries have become routine that approaches to
      structural study, novel biophysical and biochemical function analyses. However,
      several bottlenecks that GPCR-directed drugs need to conquer the problems
      including overexpression, solubilization, and purification as well as
      stabilization. The breakthroughs are to obtain efficient protein yield and
      stabilize their functional conformation which are both urgently requiring of
      effective protein synthesis system methods and optimal surfactants. Cell-free
      protein synthesis system is superior to the high yields and post-translation
      modifications, and early signs of self-assembly peptide detergents also emerged
      to superiority in purification of membrane proteins. We herein focus several
      predominant protein synthesis systems and surfactants involving the novel peptide
      detergents, and uncover the advantages of cell-free protein synthesis system with
      self-assembling peptide detergents in purification of functional GPCRs. This
      review is useful to further study in membrane proteins as well as the new drug
      exploration. 

PMID- 24566243
TI  - Comparison of the effects of 0.03 and 0.05 mg/kg midazolam with placebo on
      prevention of emergence agitation in children having strabismus surgery.
AB  - BACKGROUND: Midazolam has been widely studied for preventing emergence agitation.
      The authors previously reported that in children with sevoflurane anesthesia,
      intravenous administration of midazolam (0.05 mg/kg) before the end of surgery
      reduced the incidence of emergence agitation but prolonged the emergence time.
      This study was designed to test the hypothesis that a lower midazolam dose could
      suppress emergence agitation with minimal disturbance of the emergence time in
      children with sevoflurane anesthesia. METHODS: In this randomized, double-blind,
      placebo-controlled trial, 90 children (1 to 13 yr of age) having strabismus
      surgery were randomized to 1:1:1 to receive 0.03 mg/kg of midazolam, 0.05 mg/kg
      of midazolam, or saline just before the end of surgery. The primary outcome, the
      incidence of emergence agitation, was evaluated by using the pediatric anesthesia
      emergence delirium scale and the four-point agitation scale. The secondary
      outcome was time to emergence, defined as the time from sevoflurane
      discontinuation to the time to extubation. RESULTS: The incidence of emergence
      agitation was lower in patients given 0.03 mg/kg of midazolam (5 of 30, 16.7%)
      and patients given 0.05 mg/kg of midazolam (5 of 30, 16.7%) compared with that in
      patients given saline (13/of 30, 43.3%; P = 0.036 each). The emergence time was
      longer in patients given 0.05 mg/kg of midazolam (17.1 +/- 3.4 min, mean +/- SD)
      compared with that in patients given 0.03 mg/kg of midazolam (14.1 +/- 3.6 min; P
      = 0.0009) or saline (12.8 +/- 4.1 min; P = 0.0003). CONCLUSION: Intravenous
      administration of 0.03 mg/kg of midazolam just before the end of surgery reduces
      emergence agitation without delaying the emergence time in children having
      strabismus surgery with sevoflurane anesthesia.

PMID- 24566242
TI  - The role of efference copy in striatal learning.
AB  - Reinforcement learning requires the convergence of signals representing context,
      action, and reward. While models of basal ganglia function have well-founded
      hypotheses about the neural origin of signals representing context and reward,
      the function and origin of signals representing action are less clear. Recent
      findings suggest that exploratory or variable behaviors are initiated by a wide
      array of 'action-generating' circuits in the midbrain, brainstem, and cortex.
      Thus, in order to learn, the striatum must incorporate an efference copy of
      action decisions made in these action-generating circuits. Here we review several
      recent neural models of reinforcement learning that emphasize the role of
      efference copy signals. Also described are ideas about how these signals might be
      integrated with inputs signaling context and reward. 

PMID- 24566244
TI  - A response surface model approach for continuous measures of hypnotic and
      analgesic effect during sevoflurane-remifentanil interaction: quantifying the
      pharmacodynamic shift evoked by stimulation.
AB  - BACKGROUND: The authors studied the interaction between sevoflurane and
      remifentanil on bispectral index (BIS), state entropy (SE), response entropy
      (RE), Composite Variability Index, and Surgical Pleth Index, by using a response
      surface methodology. The authors also studied the influence of stimulation on
      this interaction. METHODS: Forty patients received combined concentrations of
      remifentanil (0 to 12 ng/ml) and sevoflurane (0.5 to 3.5 vol%) according to a
      crisscross design (160 concentration pairs). During pseudo-steady-state
      anesthesia, the pharmacodynamic measures were obtained before and after a series
      of noxious and nonnoxious stimulations. For the "prestimulation" and
      "poststimulation" BIS, SE, RE, Composite Variability Index, and Surgical Pleth
      Index, interaction models were applied to find the best fit, by using NONMEM
      7.2.0. (Icon Development Solutions, Hanover, MD). RESULTS: The authors found an
      additive interaction between sevoflurane and remifentanil on BIS, SE, and RE. For
      Composite Variability Index, a moderate synergism was found. The comparison of
      pre- and poststimulation data revealed a shift of C50SEVO for BIS, SE, and RE,
      with a consistent increase of 0.3 vol%. The Surgical Pleth Index data did not
      result in plausible parameter estimates, neither before nor after stimulation.
      CONCLUSIONS: By combining pre- and poststimulation data, interaction models for
      BIS, SE, and RE demonstrate a consistent influence of "stimulation" on the
      pharmacodynamic relationship between sevoflurane and remifentanil. Significant
      population variability exists for Composite Variability Index and Surgical Pleth
      Index.

PMID- 24566245
TI  - Tiny colored lights.

PMID- 24566246
TI  - Leadership, safety climate, and continuous quality improvement: impact on process
      quality and patient safety.
AB  - BACKGROUND: Successful amelioration of medical errors represents a significant
      problem in the health care industry. There is a need for greater understanding of
      the factors that lead to improved process quality and patient safety outcomes in
      hospitals. PURPOSE: We present a research model that shows how transformational
      leadership, safety climate, and continuous quality improvement (CQI) initiatives
      are related to objective quality and patient safety outcome measures.
      METHODOLOGY/APPROACH: The proposed framework is tested using structural equation
      modeling, based on data collected for 204 hospitals, and supplemented with
      objective outcome data from the Centers for Medicare and Medicaid Services.
      FINDINGS: The results provide empirical evidence that a safety climate, which is
      connected to the chief executive officer's transformational leadership style, is
      related to CQI initiatives, which are linked to improved process quality. A
      unique finding of this study is that, although CQI initiatives are positively
      associated with improved process quality, they are also associated with higher
      hospital-acquired condition rates, a measure of patient safety. Likewise, safety
      climate is directly related to improved patient safety outcomes. PRACTICAL
      IMPLICATIONS: The notion that patient safety climate and CQI initiatives are not
      interchangeable or universally beneficial is an important contribution to the
      literature. The results confirm the importance of using CQI to effectively
      enhance process quality in hospitals, and patient safety climate to improve
      patient safety outcomes. The overall pattern of findings suggests that
      simultaneous implementation of CQI initiatives and patient safety climate
      produces greater combined benefits.

PMID- 24566248
TI  - The influence of facility design and human resource management on health care
      professionals.
AB  - BACKGROUND: Cost control of health care services is a strategic concern for
      organizations. To lower costs, some organizations reduce staffing levels.
      However, this may not be worth the trade-off, as the quality of services will
      likely be reduced, morale among health care providers tends to suffer, and
      patient satisfaction is likely to decline. PURPOSE: The potential synergy between
      human resource management and facility design and operation was investigated to
      achieve the goal of providing cost containment strategies without sacrificing the
      quality of services and the commitment of employees. METHODOLOGY: About 700
      health care professionals from 10 acute-care hospitals participated in this cross
      sectional study. The authors used structural equation modeling to test whether
      employees' evaluations of their physical work environment and human resource
      practices were significantly associated with lower job-related anxiety, higher
      job satisfaction, and higher organizational commitment. FINDINGS: The analysis
      found that employees' evaluations of their physical work environment and human
      resource practices influenced their job-related feelings and attitudes. Perceived
      organizational support mediated this relationship. The study also found a small
      but positive interaction effect between the physical work environment and human
      resource practices. The influence of physical work environment was small, mainly
      because of the high predictive value of human resource practices and strong
      confounding variables included in the analysis. This study specifically showed
      the role of facility design in reducing job-related anxiety among caregivers.
      PRACTICE IMPLICATIONS: Preliminary evidence is provided that facility design can
      be used as a managerial tool for improving job-related attitudes and feelings of
      employees and earning their commitment. Providing a healthy and safe work
      environment can be perceived by employees as an indication that the organization
      respects them and cares about their well-being, which might be reciprocated with
      higher levels of motivation and commitment toward the organization.

PMID- 24566247
TI  - Testing a theoretical model of clinical nurses' intent to stay.
AB  - BACKGROUND: Published theoretical models of nurses' intent to stay (ITS) report
      inconsistent outcomes, and not all hypothesized models have been adequately
      tested. Research has focused on cognitive rather than emotional determinants of
      nurses' ITS. PURPOSE: The aim of this study was to empirically verify a complex
      theoretical model of nurses' ITS that includes both affective and cognitive
      determinants and to explore the influence of relational leadership on staff
      nurses' ITS. METHODOLOGY: The study was a correlational, mixed-method,
      nonexperimental design. A subsample of the Quality Work Environment Study survey
      data 2009 (n = 415 nurses) was used to test our theoretical model of clinical
      nurses' ITS as a structural equation model. RESULTS: The model explained 63% of
      variance in ITS. Organizational commitment, empowerment, and desire to stay were
      the model concepts with the strongest effects on nurses' ITS. Leadership
      practices indirectly influenced ITS. PRACTICE IMPLICATIONS: How nurses evaluate
      and respond to their work environment is both an emotional and rational process.
      Health care organizations need to be cognizant of the influence that nurses'
      feelings and views of their work setting have on their intention decisions and
      integrate that knowledge into the development of retention strategies. Leadership
      practices play an important role in staff nurses' perceptions of the workplace.
      Identifying the mechanisms by which leadership influences staff nurses'
      intentions to stay presents additional focus areas for developing retention
      strategies.

PMID- 24566250
TI  - Delivery system characteristics and their association with quality and costs of
      care: implications for accountable care organizations.
AB  - BACKGROUND: Implementation of accountable care organizations (ACOs) is currently
      underway, but there is limited empirical evidence on the merits of the ACO model.
      PURPOSE: The aim was to study the associations between delivery system
      characteristics and ACO competencies, including centralization strategies to
      manage organizations, hospital integration with physicians and outpatient
      facilities, health information technology, infrastructure to monitor community
      health and report quality, and risk-adjusted 30-day all-cause mortality and case
      mixed-adjusted inpatient costs for the Medicare population. METHODOLOGY: Panel
      data (2006-2009) were assembled from Florida and multiple sources: inpatient
      hospital discharge, vital statistics, the American Hospital Association, the
      Healthcare Information and Management Systems Society, and other databases. We
      applied a panel study design, controlling for hospital and market
      characteristics. PRINCIPAL FINDINGS: Hospitals that were in centralized health
      systems or became more centralized over the study period had significantly larger
      reductions in mortality compared with hospitals that remained freestanding.
      Surprisingly, tightly integrated hospital-physician arrangements were associated
      with increased mortality; as such, hospitals may wish to proceed cautiously when
      developing specific types of alignment with local physician organizations. We
      observed no statistically significant differences in the growth rate of costs
      across hospitals in any of the health systems studied relative to freestanding
      hospitals. Although we observed quality improvement in some organizational types,
      these outcome improvements were not coupled with the additional desired objective
      of lower cost growth. This implies that additional changes not present during our
      study period, potentially changes in provider payment approaches, are essential
      for achieving the ACO objectives of higher quality of care at lower costs.
      PRACTICE IMPLICATIONS: Provider organizations implementing ACOs should consider
      centralizing service delivery as a viable strategy to improve quality of care,
      although the strategy did not result in lower cost growth.

PMID- 24566249
TI  - Determinants of hospital fall rate trajectory groups: a longitudinal assessment
      of nurse staffing and organizational characteristics.
AB  - BACKGROUND: Patient falls in acute care hospitals represent a significant patient
      safety concern. Although cross-sectional studies have shown that fall rates vary
      widely between acute care hospitals, it is not clear whether hospital fall rates
      remain consistent over time. PURPOSE: The aim of this study was to determine
      whether hospitals can be categorized into fall rate trajectory groups over time
      and to identify nurse staffing and hospital characteristics associated with
      hospital fall rate trajectory groups. METHODOLOGY/APPROACH: We conducted a 54
      month (July 2006-December 2010) longitudinal study of U.S. acute care general
      hospitals participating in the National Database for Nursing Quality Indicators
      (2007). We used latent class growth modeling to categorize hospitals into groups
      based on their long-term fall rates. Nurse staffing and hospital characteristics
      associated with membership in the highest hospital fall rate group were
      identified using logistic regression. FINDINGS: A sample of 1,529 hospitals (mean
      fall rate of 3.65 per 1,000 patient days) contributed data to the analysis.
      Latent class growth modeling findings classified hospital into three groups based
      on fall rate trajectories: consistently high (mean fall rate of 4.96 per 1,000
      patient days), consistently medium (mean fall rate of 3.63 per 1,000 patient
      days), and consistently low (mean fall rate of 2.50 per 1,000 patient days).
      Hospitals with higher total nurse staffing (odds ratio [OR] = 0.92, 95%
      confidence interval [CI] [0.85, 0.99]), Magnet status (OR = 0.49, 95% CI [0.35,
      0.70]), and bed size greater than 300 beds (OR = 0.70, 95% CI [0.51, 0.94]) were
      significantly less likely to be categorized in the "consistently high" fall rate
      group. PRACTICE IMPLICATIONS: Over this 54-month period, hospitals were
      categorized into three groups based on long-term fall rates. Hospital-level
      factors differed among these three groups. This suggests that there may be
      hospitals in which "best practices" for fall prevention might be identified. In
      addition, administrators may be able to reduce fall rates by maintaining greater
      nurse staffing ratios as well as fostering an environment consistent with that of
      Magnet hospitals.

PMID- 24566251
TI  - Bullying among nursing staff: relationship with psychological/behavioral
      responses of nurses and medical errors.
AB  - AIM: The aim of this article is to examine the relationship between three types
      of bullying (person-related, work-related, and physically intimidating) with two
      types of outcomes (psychological/behavioral responses of nurses and medical
      errors). In addition, it investigates if the three types of bullying behaviors
      vary with age or gender of nurses and if the extent of bullying varies across
      different facilities in an institution. BACKGROUND: Nurses play an integral role
      in achieving safe and effective health care. To ensure nurses are functioning at
      their optimal level, health care organizations need to reduce negative components
      that impact nurses' job performance and their mental and physical health.
      Mitigating bullying from the workplace may be necessary to create and maintain a
      high-performing, caring, and safe hospital culture. METHODS: Using an internal e
      mail system, an e-mail requesting the participants to complete the questionnaire
      on Survey Monkey was sent to a sample of 1,078 nurses employed across three
      facilities at a university hospital system in the Midwest. Two hundred forty-one
      completed questionnaires were received with a response rate of 23%. Bullying was
      measured utilizing the Negative Acts Questionnaire-Revised (NAQ-R). Outcomes
      (psychological/behavioral responses of nurses and medical errors) were measured
      using Rosenstein and O'Daniel's (2008) modified scales. RESULTS: Person-related
      bullying showed significant positive relationships with psychological/behavioral
      responses and medical errors. Work-related bullying showed a significant positive
      relationship with psychological/behavioral responses, but not with medical
      errors. Physically intimidating bullying did not show a significant relationship
      to either outcome. Whereas person-related bullying was found to be negatively
      associated with age of nurses, physically intimidating bullying was positively
      associated with age. Male nurses experienced higher work-related bullying than
      female nurses. CONCLUSION: Findings from this study suggest that bullying
      behaviors exist and affect psychological/behavioral responses of nurses such as
      stress and anxiety and medical errors. Health care organizations should identify
      bullying behaviors and implement bullying prevention strategies to reduce those
      behaviors and the adverse effects that they may have on psychological/behavioral
      responses of nurses and medical errors.

PMID- 24566253
TI  - Path integration and coordinate systems.

PMID- 24566252
TI  - From strategy to action: how top managers' support increases middle managers'
      commitment to innovation implementation in health care organizations.
AB  - BACKGROUND: Evidence suggests that top managers' support influences middle
      managers' commitment to innovation implementation. What remains unclear is how
      top managers' support influences middle managers' commitment. Results may be used
      to improve dismal rates of innovation implementation. METHODS: We used a mixed
      method sequential design. We surveyed (n = 120) and interviewed (n = 16) middle
      managers implementing an innovation intended to reduce health disparities in 120
      U.S. health centers to assess whether top managers' support directly influences
      middle managers' commitment; by allocating implementation policies and practices;
      or by moderating the influence of implementation policies and practices on middle
      managers' commitment. For quantitative analyses, multivariable regression
      assessed direct and moderated effects; a mediation model assessed mediating
      effects. We used template analysis to assess qualitative data. FINDINGS: We found
      support for each hypothesized relationship: Results suggest that top managers
      increase middle managers' commitment by directly conveying to middle managers
      that innovation implementation is an organizational priority (beta = 0.37, p =
      .09); allocating implementation policies and practices including performance
      reviews, human resources, training, and funding (bootstrapped estimate for
      performance reviews = 0.09; 95% confidence interval [0.03, 0.17]); and
      encouraging middle managers to leverage performance reviews and human resources
      to achieve innovation implementation. PRACTICE IMPLICATIONS: Top managers can
      demonstrate their support directly by conveying to middle managers that an
      initiative is an organizational priority, allocating implementation policies and
      practices such as human resources and funding to facilitate innovation
      implementation, and convincing middle managers that innovation implementation is
      possible using available implementation policies and practices. Middle managers
      may maximize the influence of top managers' support on their commitment by
      communicating with top managers about what kind of support would be most
      effective in increasing their commitment to innovation implementation.

PMID- 24566254
TI  - Nanocrystal-based per-oral itraconazole delivery: superior in vitro dissolution
      enhancement versus Sporanox(r) is not realized in in vivo drug absorption.
AB  - Nanoscience holds true promise in enabling efficient formulation development and
      in vivo delivery of poorly water soluble drugs. The objective of this study was
      to formulate solid oral nanocrystal delivery systems of itraconazole, and thus
      enhance the oral bioavailability of the very poorly soluble drug. Nanocrystal
      suspensions were prepared by a rapid wet milling technique, after which the
      suspensions were transformed into solid dosage forms by both freeze drying and
      granulating. Finally, the obtained nanocrystalline powders were capsule-packed as
      well as compacted to tablets. After in vitro analysis, the formulations
      (nanocrystal suspension (NPs), freeze dried NPs, granulated NPs) were tested in
      vivo in a rat model, and compared with commercial itraconazole formulation
      (Sporanox). Importantly, the results indicated rapid dissolution of the
      nanocrystalline itraconazole with enhanced bioavailability compared to physical
      mixture. Drug dissolution in vitro was immediate from NPs and freeze dried
      powder, and differed significantly from the marketed product (P=0.004 and 0.002,
      correspondingly) until 30min. Freeze drying was detected to be especially
      advantageous for the solid dosage forms. It is possible to maintain the original
      character of the nanocrystals, e.g. rapid dissolution, even after tableting of
      the nanocrystalline powders. Interestingly, the marketed product out-performed
      the nanocrystalline formulations in vivo, even though the nanocrystals provided
      reasonable bioavailability of itraconazole absorption as well. The efficient in
      vitro dissolution enhancement of the nanocrystalline formulations compared to
      Sporanox(r) was not realized in in vivo drug absorption. 

PMID- 24566255
TI  - Native chemical ligation for conversion of sequence-defined oligomers into
      targeted pDNA and siRNA carriers.
AB  - Native chemical ligation (NCL) was established for the conversion of sequence
      defined oligomers of different topologies into targeted and PEG shielded pDNA and
      siRNA carriers. From an existing library of non-targeted oligoethanamino amides,
      six oligomers containing N-terminal cysteines were selected as cationic cores, to
      which monodisperse polyethylene glycol (PEG) containing terminal folic acid as
      targeting ligand (or terminal alanine as targeting negative control ligand) were
      attached by NCL. Ligated conjugates plus controls (in sum 18 oligomers) were
      evaluated for pDNA or siRNA gene delivery. Biophysical characteristics including
      nucleic acid binding in the absence or presence of serum, as well as biological
      activities in cellular uptake and gene transfer (or gene silencing, respectively)
      were determined. In most cases, the folic acid-PEG-ligated oligomers displayed a
      strongly improved cellular binding, uptake and gene transfer into receptor
      positive KB cells as compared to the alanine-PEG controls. Changing the
      topological structures by increasing the number of cationic arms, adding tyrosine
      trimers as polyplex stabilizing domains, or histidines facilitating endosomal
      escape resulted in beneficial gene transfer characteristics. The screen revealed
      different requirements for pDNA and siRNA delivery. A folate-PEG ligated
      histidinylated four-arm oligomer was most effective for pDNA delivery but
      inactive for siRNA, whereas a folate-PEG-ligated three-arm oligomer with tyrosine
      trimer modifications was most effective in siRNA mediated gene silencing. The
      results demonstrate the site-selective NCL reaction as powerful method to modify
      existing oligomers. Thus multifunctional targeted carriers can be obtained with
      ease and used to identify lead structures for subsequent in vivo delivery. 

PMID- 24566256
TI  - Quantitative evaluation of the improvement in the pharmacokinetics of a nucleic
      acid drug delivery system by dynamic PET imaging with (18)F-incorporated
      oligodeoxynucleotides.
AB  - Recently, we demonstrated the utility of positron emission tomography (PET)
      imaging-based pharmacokinetic evaluation studies for preclinical experiments and
      microdose clinical trials, mainly focused on low molecular weight compounds. In
      order to investigate the pharmacokinetics of nucleic acid drugs and their drug
      delivery systems (DDSs) in vivo by using PET imaging, we developed a novel and
      efficient method for radiolabeling oligodeoxynucleotides with the positron
      emitting radionuclide (18)F (stoichiometry-focused Huisgen-type (18)F labeling).
      By using this method, we succeeded in synthesizing a variety of (18)F-labeled
      oligodeoxynucleotides with not only phosphodiesters (PO) in natural forms, but
      also phosphorothioate (PS) and bridged nucleic acid (BNA) in artificial forms,
      and then performed PET studies and radioactive metabolite analyses of these (18)F
      labeled oligodeoxynucleotides. The tissue-distribution and dynamic changes in
      radioactivity showed significantly different profiles between these antisense
      oligodeoxynucleotides. The radioactivity of (18)F-labeled PO-DNA and PO-BNA
      rapidly accumulated in the kidneys and liver and then moved to the renal medulla,
      ureter, bladder, and intestine. However, the radioactivity of (18)F-labeled PS
      DNA and PS-BNA, possessing PS backbone structures, was retained in the blood for
      relatively long periods and then gradually accumulated in the liver and kidneys.
      The metabolite analysis showed that (18)F-labeled PO-DNA rapidly degraded by 5min
      and (18)F-labeled PO-BNA gradually degraded over time by 60min. Conversely, (18)F
      labeled PS-DNA and PS-BNA were shown to be much more stable. To demonstrate the
      usefulness of the PET imaging technique for evaluating the improved targeting
      potential of the DDS, we designed and synthesized a cholesterol-modified
      oligodeoxynucleotide, that we developed as an antisense nucleic acid drug against
      proprotein convertase subtilisin/kexin type 9 (PCSK9) for hypercholesterolemia
      therapy, and evaluated its pharmacokinetics using PET imaging. As expected, the
      (18)F-labeled cholesterol-modified PS-BNA-type oligodeoxynucleotide showed much
      higher and more rapid accumulation in the delivery target organ, that is, the
      liver, which encourages us to develop this drug. These results suggest that
      dynamic PET studies using (18)F-incorporated oligodeoxynucleotide synthesized by
      stoichiometry-focused Huisgen-type labeling is useful for quantitative
      pharmacokinetic evaluation of nucleic acid drugs and their delivery systems. 

PMID- 24566258
TI  - Organoleptic assessment of halitosis for dental professionals--general
      recommendations.
AB  - An organoleptic assessment of an odor is defined as a method that can measure the
      strength of target odors and expresses the value in terms of a point or number
      with reference to a pre-defined organoleptic scale. Organoleptic assessments are
      performed using different scales and are used widely in industry (e.g. for
      measuring the effectiveness of anti-odor agents), in research (to discover
      relationships between bad breath and microbiology of the tongue, or the
      generation of particular volatile compounds), but it is also a prerequisite for
      the diagnosis of halitosis in individual patients required before directing
      appropriate treatment. An organoleptic assessment of halitosis patients may be
      carried out in specialized institutions but--based on the fact that in most cases
      the odor originates from oral structures--also by dental professionals including
      general dental practitioners (GDPs). Thus, this paper describes the scientific
      background for recommendations on how a GDP or dental hygienist or general
      practitioner with cases of bad breath should use organoleptic methods as a valid
      approach to assess malodor in patients, with a view to diagnosis and treatment,
      and subsequent treatment monitoring.

PMID- 24566259
TI  - French journal calls for domperidone to be withdrawn.

PMID- 24566260
TI  - Quantification of tau in cerebrospinal fluid by immunoaffinity enrichment and
      tandem mass spectrometry.
AB  - BACKGROUND: Cerebrospinal fluid (CSF) tau is a common biomarker for Alzheimer
      disease (AD). Measurements of tau have historically been performed using
      immunoassays. Given the molecular diversity of tau in CSF, the selectivity of
      these immunoassays has often been questioned. Therefore, we aimed to develop an
      analytically sensitive and selective immunoaffinity liquid chromatography-tandem
      mass spectrometry (LC-MS/MS) (IA-MS) assay. METHODS: IA-MS sample analysis
      involved the addition of an internal standard, immunoaffinity purification of tau
      using a tau monoclonal antibody coupled to magnetic beads, trypsin digestion, and
      quantification of a surrogate tau peptide by LC-MS/MS using a Waters Trizaic
      nanoTile ultraperformance LC microfluidic device. Further characterization of tau
      peptides was performed by full-scan MS using a Thermo Orbitrap LC-MS. CSF samples
      from a cohort of age-matched controls and patients with AD were analyzed by the
      IA-MS method as well as a commercially available immunoassay. RESULTS: The IA-MS
      assay had intra- and interassay imprecision values of 3.2% to 8.1% CV and 7.8% to
      18.9% C, respectively, a mean recovery of 106%, and a limit of quantification of
      0.25 pmol/L and was able to quantify tau concentrations in all human specimens
      tested. The IA-MS assay showed a correlation of R(2) = 0.950 against a total-tau
      immunoassay. In patients with AD, tau was increased approximately 2-fold.
      CONCLUSIONS: Combining immunoaffinity enrichment with microflow LC-MS/MS analysis
      is an effective approach for the development of a highly selective assay to
      measure total tau and, potentially, other posttranslationally modified forms of
      tau in CSF.

PMID- 24566257
TI  - Re-examining class-I presentation and the DRiP hypothesis.
AB  - MHC class I molecules present peptides derived from intracellular proteins,
      enabling immune surveillance by CD8(+) T cells and the elimination of virus
      infected and cancerous cells. It has been argued that the dominant source of MHC
      class I-presented peptides is through proteasomal degradation of newly
      synthesized defective proteins, termed defective ribosomal products (DRiPs).
      Here, we critically examine the DRiP hypothesis and discuss recent studies
      indicating that antigenic peptides are generated from the entire proteome and not
      just from failures in protein synthesis or folding. 

PMID- 24566261
TI  - Tanjungides A and B: new antitumoral bromoindole derived compounds from Diazona
      cf formosa. isolation and total synthesis.
AB  - Tanjungides A (1) (Z isomer) and B (2) (E isomer), two novel dibrominated indole
      enamides, have been isolated from the tunicate Diazona cf formosa. Their
      structures were determined by spectroscopic methods including HRMS, and extensive
      1D and 2D NMR. The stereochemistry of the cyclised cystine present in both
      compounds was determined by Marfey's analysis after chemical degradation and
      hydrolysis. We also report the first total synthesis of these compounds using
      methyl 1H-indole-3-carboxylate as starting material and a linear sequence of 11
      chemical steps. Tanjungides A and B exhibit significant cytotoxicity against
      human tumor cell lines. 

PMID- 24566262
TI  - The marine sponge-derived inorganic polymers, biosilica and polyphosphate, as
      morphogenetically active matrices/scaffolds for the differentiation of human
      multipotent stromal cells: potential application in 3D printing and distraction
      osteogenesis.
AB  - The two marine inorganic polymers, biosilica (BS), enzymatically synthesized from
      ortho-silicate, and polyphosphate (polyP), a likewise enzymatically synthesized
      polymer consisting of 10 to >100 phosphate residues linked by high-energy
      phosphoanhydride bonds, have previously been shown to display a morphogenetic
      effect on osteoblasts. In the present study, the effect of these polymers on the
      differential differentiation of human multipotent stromal cells (hMSC),
      mesenchymal stem cells, that had been encapsulated into beads of the
      biocompatible plant polymer alginate, was studied. The differentiation of the
      hMSCs in the alginate beads was directed either to the osteogenic cell lineage by
      exposure to an osteogenic medium (mineralization activation cocktail;
      differentiation into osteoblasts) or to the chondrogenic cell lineage by
      incubating in chondrocyte differentiation medium (triggering chondrocyte
      maturation). Both biosilica and polyP, applied as Ca2+ salts, were found to
      induce an increased mineralization in osteogenic cells; these inorganic polymers
      display also morphogenetic potential. The effects were substantiated by gene
      expression studies, which revealed that biosilica and polyP strongly and
      significantly increase the expression of bone morphogenetic protein 2 (BMP-2) and
      alkaline phosphatase (ALP) in osteogenic cells, which was significantly more
      pronounced in osteogenic versus chondrogenic cells. A differential effect of the
      two polymers was seen on the expression of the two collagen types, I and II.
      While collagen Type I is highly expressed in osteogenic cells, but not in
      chondrogenic cells after exposure to biosilica or polyP, the upregulation of the
      steady-state level of collagen Type II transcripts in chondrogenic cells is
      comparably stronger than in osteogenic cells. It is concluded that the two
      polymers, biosilica and polyP, are morphogenetically active additives for the
      otherwise biologically inert alginate polymer. It is proposed that alginate,
      supplemented with polyP and/or biosilica, is a suitable biomaterial that promotes
      the growth and differentiation of hMSCs and might be beneficial for application
      in 3D tissue printing of hMSCs and for the delivery of hMSCs in fractures,
      surgically created during distraction osteogenesis.

PMID- 24566263
TI  - Krempfielins N-P, New anti-inflammatory eunicellins from a Taiwanese soft coral
      Cladiella krempfi.
AB  - Three new eunicellin-type diterpenoids, krempfielins N-P (1-3), were isolated
      from a Taiwanese soft coral Cladiella krempfi. The structures of the new
      metabolites were elucidated by extensive spectroscopic analysis and by comparison
      with spectroscopic data of related known compounds. Compound 3 exhibited activity
      to inhibit superoxide anion generation. Both 1 and 3, in particular 1, were shown
      to display significant anti-inflammatory activity by inhibiting the elastase
      release in FMLP/CB-induced human neutrophils. 

PMID- 24566265
TI  - Behaviour, attitudes and awareness concerning sun exposure in adolescents on the
      Costa del Sol.
AB  - BACKGROUND: A history of sunburn and cumulative sun exposure during adolescence
      are the most important risk factors for the development of skin cancer. Skin
      cancer can be prevented by reducing sun exposure, particularly during
      adolescence, which is precisely the age group that could best benefit from
      primary prevention campaigns. OBJECTIVE: To determine the behaviour, attitudes
      and understanding of adolescents concerning sun exposure. METHODS: This cross
      sectional descriptive study undertaken during 2011 included secondary school
      adolescents from randomly selected schools on the Costa del Sol, southern Spain.
      A validated beachside questionnaire was used to record data on demographics, skin
      colour, phototype, sun exposure habits, sunburns, practices, attitudes and
      knowledge about the sun. RESULTS: The study involved 270 students, aged 14-17
      years, from 11 schools; 50.4% were female, 43.7% were aged 14 years, and 85.9%
      were Spanish. Most had a light skin colour (49.3%) and phototypes III (42.2%) or
      IV (34.8%). Most (71%) went to the beach on more than 16 days and 74.4% had had
      sunburn the previous summer. Sun cream was used by 47.8% and 1.1% wore long
      sleeves or trousers. Concerning attitudes, 60.7% stated they felt better when
      they were tanned, and concerning understanding, most were aware of the harmful
      effects of the sun on the skin. CONCLUSION: Adolescents comprise a special risk
      group with a positive attitude towards tanning. Further studies are required to
      assess educational stategies in order to reduce the desire to have a suntan, and
      improve sun protection practices and habits targeted at this age group.

PMID- 24566266
TI  - Comparison of different solid-phase extraction materials for the determination of
      fluoroquinolones in chicken plasma by LC-MS/MS.
AB  - Fluoroquinolones are synthetic antibiotics which are frequently used in
      veterinary medicine e.g. for the treatment of poultry. Their specific importance
      is based on the fact that they are regarded as antibiotics of last resort because
      of their broad spectrum of action against Gram-negative and -positive bacteria.
      Here, a new and sensitive method for the simultaneous determination of four
      fluoroquinolones (marbofloxacin, ciprofloxacin, enrofloxacin and difloxacin) in
      chicken plasma by LC-MS/MS was developed. Solid-phase extraction was chosen for
      sample preparation because a selective sample clean-up is combined with an
      effective extraction. Various solid-phase extraction materials including polymer
      based reversed-phase, silica-based reversed-phase and mixed-mode sorbents were
      compared. Selection criteria were analyte recovery, sample extract purity and
      economical aspects (analysis time and elution solvent volume). Best recoveries
      and minimized elution solvent volumes were achieved using polymeric reversed
      phase cartridges. However, post-column infusion experiments revealed that the
      analysis is influenced by co-eluting matrix components. Hence, a combination of a
      mixed-mode anion-exchange cartridge and a mixed-mode cation-exchange cartridge
      was used as final extraction method. This method yield slightly lower analyte
      recoveries compared to polymeric-reversed-phase cartridges but exhibit no matrix
      effects. Recoveries of spiked chicken plasma ranged from 61.9% to 84.8% with an
      inter-day precision of generally less than 12%. LODs are between 0.03 and
      0.05MUg/L; LOQs are between 0.08 and 0.16MUg/L. Maximum plasma concentrations of
      chickens medicated with an enrofloxacin dosage of 3mg/kg bodyweight were
      38.9MUg/L for enrofloxacin and 3.3MUg/L for its main metabolite ciprofloxacin. 

PMID- 24566267
TI  - Hollow fiber liquid-phase microextraction combined with ultra-high performance
      liquid chromatography-tandem mass spectrometry for the simultaneous determination
      of naloxone, buprenorphine and norbuprenorphine in human plasma.
AB  - A hollow fiber liquid phase microextraction (HF-LPME) combined with ultra-high
      performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method
      was developed for the extraction and determination of naloxone (NLX),
      buprenorphine (BP) and its major metabolite norbuprenorphine (NBP) in human
      plasma. The optimum extraction conditions of HF-LPME were: the porous of
      polyvinylidene fluoride (PVDF) hollow fiber was full of component solvent (1
      octanol/chloroform/toluene, 2/4/4), the pH of donor phase was 8.7, the extraction
      time was 30min and stirring speed was 1000 revolutions per minute (rpm). The
      UHPLC-MS/MS method was performed with Waters ACQUITY UPLCTM BEH C18, 50mm*2.1mm,
      1.7MUm, using methanol-0.2%formic acid as mobile phase with a gradient elution at
      a flow rate of 0.25mL/min. The target compounds were detected under a tandem
      quadrupole mass spectrometer in positive electrospray ionization (ESI) mode, then
      analyzed in multiple reaction monitoring (MRM) mode and the isotope internal
      standard method was used for quantification. The results showed that linearities
      were in the range of 0.1-25ng/mL (R>0.996). The limits of detection (LOD) of
      BP/NBP/NLX were 0.05/0.05/0.025ng/mL and the limits of quantitation (LOQ) of
      BP/NBP/NLX were 0.1/0.1/0.05ng/mL, respectively. The spiked recoveries were in
      the range of 92.1-106.0% with relative standard deviation (RSD) values were less
      than 15%. This method was simple, inexpensive, sensitive and has been
      successfully used to quantify plasma samples from patients included in a clinical
      pharmacogenetic study. 

PMID- 24566268
TI  - Iriflophenone-3-C-glucoside from Cyclopia genistoides: isolation and quantitative
      comparison of antioxidant capacity with mangiferin and isomangiferin using on
      line HPLC antioxidant assays.
AB  - The benzophenone, iriflophenone-3-C-glucoside, was isolated from Cyclopia
      genistoides using a combination of fluid-fluid extraction, high performance
      counter-current chromatography (HPCCC) and semi-preparative high performance
      liquid chromatography (HPLC). The microplate oxygen radical absorbance capacity
      (ORAC) assay, with fluorescein as probe, was adapted for use in an on-line HPLC
      configuration. The method was validated using a mixture of authentic standards
      including iriflophenone-3-C-glucoside, and the xanthones, mangiferin and
      isomangiferin. Trolox (6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid)
      was included in the mixture for calculation of Trolox equivalent antioxidant
      capacity (TEAC) values. Using the on-line HPLC-ORAC assay, as well as 2,2
      diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azinobis-(3-ethylbenzothiazoline-6
      sulfonic acid) (ABTS(+)) on-line assays, the antioxidant activity of
      iriflophenone-3-C-glucoside and isomangiferin was demonstrated for the first
      time. Iriflophenone-3-C-glucoside presented no radical scavenging ability against
      DPPH, but scavenged ABTS(+) and peroxyl radicals (TEACABTS of 1.04 and TEACORAC
      of 3.61). Isomangiferin showed slightly lower antioxidant capacity than
      mangiferin against DPPH (TEACDPPH of 0.57 vs. 0.62), but higher capacity against
      ABTS(+) (TEACABTS of 1.82 vs. 1.67) and peroxyl radical (TEACORAC of 4.14 vs.
      3.69) than mangiferin. The on-line HPLC-ORAC assay was shown to be more sensitive
      for radical scavengers, but at the same time less selective for rapid radical
      scavengers than the DPPH assay. 

PMID- 24566269
TI  - In vitro microbial culture models and their application in drug development.
AB  - Drug development faces its nemesis in the form of drug resistance. The rate of
      bacterial resistance to antibiotics, or tumor resistance to chemotherapy
      decisively depends on the surrounding heterogeneous tissue. However, in vitro
      drug testing is almost exclusively done in well stirred, homogeneous
      environments. Recent advancements in microfluidics and microfabrication introduce
      opportunities to develop in vitro culture models that mimic the complex in vivo
      tissue environment. In this review, we will first discuss the design principles
      underlying such models. Then we will demonstrate two types of microfluidic
      devices that combine stressor gradients, cell motility, large population of
      competing/cooperative cells and time varying dosage of drugs. By incorporating
      ideas from how natural selection and evolution move drug resistance forward, we
      show that drug resistance can occur at much greater rates than in well-stirred
      environments. Finally, we will discuss the future direction of in vitro microbial
      culture models and how to extend the lessons learned from microbial systems to
      eukaryotic cells. 

PMID- 24566271
TI  - Toxicity of carboxylated carbon nanotubes in endothelial cells is attenuated by
      stimulation of the autophagic flux with the release of nanomaterial in autophagic
      vesicles.
AB  - Carbon nanotubes (CNTs) exhibit a number of unique properties that make them
      attractive for various nanomedicine applications including their intravascular
      use. Therefore, the vascular toxicity of CNTs is a critical safety concern and
      methods of CNTs toxicity modulation are of great interest. Here, we report that
      carboxylated multiwalled carbon nanotubes (MWCNTs) induce a decrease in viability
      of cultured human umbilical vein endothelial cells (HUVECs) associated with the
      profound accumulation of autophagosomes. This autophagosome accumulation was mTOR
      kinase independent and was caused by blockade of the autophagic flux rather than
      by activation of autophagy. Stimulation of the autophagic flux with 1nmol/L
      bafilomycin A1 attenuated the cytotoxicity of carboxylated MWCNTs in HUVECs and
      was associated with the extracellular release of the nanomaterial in autophagic
      microvesicles. Thus, pharmacological stimulation of the autophagic flux may
      represent a new method of cytoprotection against toxic effects of nanomaterials.
      FROM THE CLINICAL EDITOR: This study investigates the mechanisms of toxicity of
      multiwalled carbon nanutubes on human endothelial cells, concluding that
      pharmacological stimulation of autophagic flux may represent a new method of
      cytoprotection against the toxic effects of these nanomaterials.

PMID- 24566270
TI  - Lipid-polymer nanoparticles encapsulating curcumin for modulating the vascular
      deposition of breast cancer cells.
AB  - Vascular adhesion and endothelial transmigration are critical steps in the
      establishment of distant metastasis by circulating tumor cells (CTCs). Also,
      vascular inflammation plays a pivotal role in steering CTCs out of the blood
      stream. Here, long circulating lipid-polymer nanoparticles encapsulating curcumin
      (NANOCurc) are proposed for modulating the vascular deposition of CTCs. Upon
      treatment with NANOCurc, the adhesion propensity of highly metastatic breast
      cancer cells (MDA-MB-231) onto TNF-alpha stimulated endothelial cells (HUVECs)
      reduces by ~70%, in a capillary flow. Remarkably, the CTCs vascular deposition
      already reduces up to ~50% by treating solely the inflamed HUVECs. The CTCs
      arrest is mediated by the interaction between ICAM-1 on HUVECs and MUC-1 on
      cancer cells, and moderate doses of curcumin down-regulate the expression of both
      molecules. This suggests that NANOCurc could prevent metastasis and limit the
      progression of the disease by modulating vascular inflammation and impairing the
      CTCs arrest. FROM THE CLINICAL EDITOR: In this novel study, lipid nanoparticles
      encapsulating curcumin were able to prevent metastasis formation and limited the
      progression of the disease by modulating vascular inflammation and impairing the
      circulating tumor cells' arrest as a result of down-regulation of ICAM1 and MUC1
      in a highly metastatic breast cancer cell line model.

PMID- 24566272
TI  - Activation of multiple signaling pathways during the differentiation of
      mesenchymal stem cells cultured in a silicon nanowire microenvironment.
AB  - Mesenchymal stem cells (MSC) offer an optimal source for bone tissue engineering
      due to their capability of undergoing multilineage differentiation, where the
      mechanical properties of the microenvironment of MSCs are vital for osteochondral
      formation. However, the mechanisms of how mechanical and microenvironmental cues
      control osteogenesis and chondrogenesis are yet to be elucidated. In this study,
      we investigated the effects of vertically aligned silicon nanowire (SiNW) array
      on the differentiation of MSCs and the associated molecular mechanisms involved
      in osteogenesis and chandrogenesis. The results showed that the microenvironment
      of SiNW array activated a number of mechanosensitive pathways (including
      Integrin, TGF-beta/BMP, Akt, MAPK, Insulin, and Wnt pathways) in MSCs, which
      converged to stimulate the osteogenesis and chondrogenesis via the Ras-Raf-MEK
      ERK cascade. FROM THE CLINICAL EDITOR: This study reports on the mechanisms and
      microenvironmental influence of osteogenesis and chondrogenesis by mesenchymal
      stem cells interacting with vertically aligned silicon nanowire scaffolds.

PMID- 24566273
TI  - Nanopore film based enrichment and quantification of low abundance hepcidin from
      human bodily fluids.
AB  - Endogenous peptides that represent biological and pathological information of
      disease have attracted interest for diagnosis. However, the extraction of those
      low abundance peptides is still a challenge because of the complexity of human
      bodily fluids (HBF). Hepcidin, a peptide hormone, has been recognized as a
      biomarker for iron-related diseases. There is no rapid and reliable way to enrich
      them from HBF. Here we describe a peptide extraction approach based on nanoporous
      silica thin films to successfully detect hepcidin from HBF. Cooperative functions
      of nanopore to biomolecule, including capillary adsorption, size-exclusion and
      electrostatic interaction, were systematically investigated to immobilize the
      target peptide. To promote this new approach to clinical practices, we further
      applied it to successfully assay the hepcidin levels in HBF provided by healthy
      volunteers and patients suffering from inflammation. Our finding provides a high
      throughput, rapid, label-free and cost-effective detection method for capturing
      and quantifying low abundance peptides from HBF. FROM THE CLINICAL EDITOR:
      Diagnosing diseases with low concentration peptide biomarkers remains
      challenging. This team of authors describes a peptide extraction approach based
      on nanoporous silica thin films to successfully detect low concentrations of
      hepcidin from human body fluids collected from 119 healthy volunteers and 19
      inflammation patients.

PMID- 24566275
TI  - Anti-angiogenic effect of bare titanium dioxide nanoparticles on pathologic
      neovascularization without unbearable toxicity.
AB  - Local application requires fewer nanoparticles than systemic delivery to achieve
      effective concentration. In this study, we investigated the potential toxicity
      and efficacy of bare titanium dioxide (TiO2) nanoparticles by local
      administration into the eye. Mono-disperse, 20nm-size TiO2 nanoparticles did not
      affect the viability of retinal constituent cells within certain range of
      concentrations (~1.30MUg/mL). Furthermore, local delivery of TiO2 nanoparticles
      did not induce any significant toxicity at the level of gene expression and
      histologic integrity in the retina of C57BL/6 mice. Interestingly, at the low
      concentration (130ng/mL) without definite toxicity, these nanoparticles
      suppressed in vitro angiogenesis processes and in vivo retinal neovascularization
      in oxygen-induced retinopathy mice when they are administered intravitreally.
      Taken together, our results demonstrate that even TiO2 nanoparticles can be
      safely utilized for the treatment of retinal diseases at the adequate
      concentration levels, especially through local administration. FROM THE CLINICAL
      EDITOR: In this paper the local application of titanium dioxide is described as a
      local treatment for retinal diseases associated with neovascularization. While
      these nanoparticles have known systemic toxicity, this work demonstrates that
      when applied locally in a mouse model, they can be used without observable
      toxicity even in their native forms.

PMID- 24566274
TI  - Local hyperthermia treatment of tumors induces CD8(+) T cell-mediated resistance
      against distal and secondary tumors.
AB  - Combinatorial use of iron oxide nanoparticles (IONPs) and an alternating magnetic
      field (AMF) can induce local hyperthermia in tumors in a controlled and uniform
      manner. Heating B16 primary tumors at 43 degrees C for 30 min activated dendritic
      cells (DCs) and subsequently CD8(+) T cells in the draining lymph node (dLN) and
      conferred resistance against rechallenge with B16 (but not unrelated Lewis Lung
      carcinoma) given 7 days post hyperthermia on both the primary tumor side and the
      contralateral side in a CD8(+) T cell-dependent manner. Mice with heated primary
      tumors also resisted rechallenge given 30 days post hyperthermia. Mice with
      larger heated primary tumors had greater resistance to secondary tumors. No
      rechallenge resistance occurred when tumors were heated at 45 degrees C. Our
      results demonstrate the promising potential of local hyperthermia treatment
      applied to identified tumors in inducing anti-tumor immune responses that reduce
      the risk of recurrence and metastasis. FROM THE CLINICAL EDITOR: Local heating of
      tumors via iron oxide NPs and an alternating magnetic field led to activation of
      anti-cancer CD8 T cells, which resulted in resistance against re-challenge and
      greater resistance to secondary tumors. Similar local heating-based strategies
      may become an important weapon in enhancing tumor elimination via a naturally
      existing but attenuated immune response.

PMID- 24566276
TI  - Nanoparticle targeting to diseased vasculature for imaging and therapy.
AB  - Significant challenges remain in targeting drugs to diseased vasculature; most
      important being rapid blood flow with high shear, limited availability of stable
      targets, and heterogeneity and recycling of cellular markers. We developed
      nanoparticles (NPs) to target degraded elastic lamina, a consistent pathological
      feature in vascular diseases. In-vitro organ and cell culture experiments
      demonstrated that these NPs were not taken up by cells, but instead retained
      within the extracellular space; NP binding was proportional to the extent of
      elastic lamina damage. With three well-established rodent models of vascular
      diseases such as aortic aneurysm (calcium chloride mediated aortic injury in
      rats), atherosclerosis (fat-fed apoE-/- mice), and vascular calcification
      (warfarin + vitamin K injections in rats), we show precise NPs spatial targeting
      to degraded vascular elastic lamina while sparing healthy vasculature when NPs
      were delivered systemically. Nanoparticle targeting degraded elastic lamina is
      attractive to deliver therapeutic or imaging agents to the diseased vasculature.
      FROM THE CLINICAL EDITOR: This novel work focuses on nanoparticle targeting of
      degraded elastic lamina in a variety of diseases, including atherosclerosis,
      vascular calcification, and aneurysm formation, and demonstrates the feasibility
      to deliver therapeutic or imaging agents to the diseased vasculature.

PMID- 24566278
TI  - The arrest of drivers under the influence as a predictor of subsequent social
      disadvantage and death.
AB  - BACKGROUND: The association between DUI (driving under the influence) and
      disadvantaged social background has been shown in cross-sectional studies, but
      less is known about the processes behind this phenomenon. We aimed to examine the
      effect of DUI arrest on subsequent social disadvantage in Finland during 1993
      2006 to provide more understanding about the dynamics of DUI and marginalization
      and to study DUI arrest as a potential point of intervention. METHODS: In this
      longitudinal, register-based study the Register of DUI suspects (n=68894) was
      linked with the Employment Register. An age- and gender-matched reference
      population (n=67740) was drawn from the general Finnish population. A multi-state
      model was used to estimate the transition intensities between three different
      states (advantaged social status/disadvantaged social status/death) among three
      different DUI groups (alcohol only, prescription drugs, illicit drugs). RESULTS:
      Compared to references, the movement of DUI suspects between different social
      states was more dynamic in that they were more likely to either move to a
      disadvantaged social state or to an improved status (except DUI suspects using
      prescription drugs). A DUI's relative risk of death compared to references was
      high, especially if currently in advantaged social status. The effect of DUI did
      not diminish over time. CONCLUSIONS: Driving under the influence is associated
      with an increased long-term risk for social disadvantage. DUI arrest could serve
      as an opportunity for intervention in the marginalization process.

PMID- 24566277
TI  - A steroid-mimicking nanomaterial that mediates inhibition of human lung mast cell
      responses.
AB  - Water-soluble fullerenes can be engineered to regulate activation of mast cells
      (MC) and control MC-driven diseases in vivo. To further understand their anti
      inflammatory mechanisms a C70-based fullerene conjugated to four myo-inositol
      molecules (C70-I) was examined in vitro for its effects on the signaling pathways
      leading to mediator release from human lung MC. The C70-I fullerene stabilizes MC
      and acts synergistically with long-acting beta2-adrenergic receptor agonists
      (LABA) to enhance inhibition of MC mediator release through FcepsilonRI
      simulation. The inhibition was paralleled by the upregulation of dual-specificity
      phosphatase one (DUSP1) gene and protein levels. Concomitantly, increases in MAPK
      were blunted in C70-I treated cells. The increase in DUSP1 expression was due to
      the ability of C70-I to prevent the ubiquitination and degradation of DUSP1.
      These findings identify a mechanism of how fullerenes inhibit inflammatory
      mediator release from MC and suggest they could potentially be an alternative
      therapy for steroid resistant asthmatics. FROM THE CLINICAL EDITOR: This study
      investigates the role and mechanism of action of fullerenes in deactivating mast
      cell-based inflammation, paving the way to the development of a novel, non
      steroid therapy in reactive airway disease.

PMID- 24566279
TI  - Genetic algorithm-artificial neural network and adaptive neuro-fuzzy inference
      system modeling of antibacterial activity of annatto dye on Salmonella
      enteritidis.
AB  - Annatto is commonly used as a coloring agent in the food industry and has
      antimicrobial and antioxidant properties. In this study, genetic algorithm
      artificial neural network (GA-ANN) and adaptive neuro-fuzzy inference system
      (ANFIS) models were used to predict the effect of annatto dye on Salmonella
      enteritidis in mayonnaise. The GA-ANN and ANFIS were fed with 3 inputs of annatto
      dye concentration (0, 0.1, 0.2 and 0.4%), storage temperature (4 and 25 degrees
      C) and storage time (1-20 days) for prediction of S. enteritidis population. Both
      models were trained with experimental data. The results showed that the annatto
      dye was able to reduce of S. enteritidis and its effect was stronger at 25
      degrees C than 4 degrees C. The developed GA-ANN, which included 8 hidden
      neurons, could predict S. enteritidis population with correlation coefficient of
      0.999. The overall agreement between ANFIS predictions and experimental data was
      also very good (r=0.998). Sensitivity analysis results showed that storage
      temperature was the most sensitive factor for prediction of S. enteritidis
      population. 

PMID- 24566280
TI  - Are statewide restaurant and bar smoking bans associated with reduced cigarette
      smoking among those with mental illness?
AB  - BACKGROUND: Smoke-free air laws have effectively reduced cigarette consumption at
      the population level; however, the influence of these policies on smoking among
      those with mental illness is unclear. We examined whether associations between
      statewide restaurant/bar smoking bans and cigarette smoking varied by psychiatric
      diagnoses and gender. METHODS: We analyzed data from the National Epidemiologic
      Survey on Alcohol and Related Conditions (NESARC, Wave 1: 2001-2002; Wave 2: 2004
      2005; n = 7,317 smokers). All analyses were stratified by gender. We examined
      whether tobacco cessation was associated with the interaction between ban
      implementation and Wave 1 psychiatric diagnoses (alcohol use disorder [AUD],
      anxiety disorder [AD], or mood disorder), adjusting for relevant covariates.
      Among those who continued to use tobacco at Wave 2, we examined associations
      between Wave 2 cigarettes per day (CPD) and the diagnoses * ban interactions,
      controlling for Wave 1 CPD and other relevant covariates. RESULTS: Among men with
      an AUD and women with an AD, ban implementation was associated with 6% and 10%
      greater probability of tobacco cessation at Wave 2, respectively. Among men in
      the overall sample, ban implementation was associated with smoking 0.8 fewer CPD
      at Wave 2. Associations with CPD were nonsignificant among women. Interactions
      between ban implementation and psychiatric diagnoses were also nonsignificant
      when examining CPD, suggesting consistent reductions in CPD among men but not
      among women. CONCLUSIONS: This study provided the first evidence that statewide
      restaurant/bar smoking bans may be associated with reduced smoking among those
      with select psychiatric conditions.

PMID- 24566282
TI  - Anti-tuberculosis treatment enhances the production of IL-22 through reducing the
      frequencies of regulatory B cell.
AB  - IL-22 has been suggested to play an important role in immune response against
      Mycobacterium tuberculosis infection. However, the exact role of IL-22 in human
      tuberculosis (TB) infection remains unclear and the regulatory mechanism of IL-22
      response in human TB is unknown. In this study, we observed that successful anti
      tuberculosis treatment induced an enhanced and sustained M. tuberculosis antigen
      specific IL-22 response, correlated with the decrease of the frequencies of
      CD19(+)CD5(+)CD1d(+) regulatory B cells. We also found that depletion of CD19(+)
      B cells significantly enhanced M. tuberculosis antigen-specific IL-22 production
      by peripheral blood mononuclear cells. More importantly, we observed that
      purified CD19(+) B cells, and more efficiently, CD19(+)CD5(+)CD1d(+) regulatory B
      cells, suppressed IL-22 production. In summary, we showed here for the first time
      that effective anti-tuberculosis treatment restores M. tuberculosis antigen
      specific IL-22 response through a novel mechanism by reducing the frequencies of
      CD19(+)CD5(+)CD1d(+) regulatory B cells in human TB. 

PMID- 24566283
TI  - Differentiation of human mononuclear phagocytes increases their innate response
      to Mycobacterium tuberculosis infection.
AB  - The heterogeneity of mononuclear phagocytes, partially explained by cell
      differentiation, influences the activation of innate responses. It has been
      reported that Mycobacterium tuberculosis inhibits monocyte differentiation into
      either dendritic cells or macrophages. To evaluate whether the activation of
      effector mechanisms against M. tuberculosis differ between less and more
      differentiated mononuclear phagocytes, we compared monocytes differentiated in
      vitro for 24 h (MON24) and 120 h (MDM120) infected with M. tuberculosis H37Rv,
      H37Ra and the clinical isolate UT127 at different multiplicity of infection.
      MDM120 phagocytosed more M. tuberculosis, inhibited mycobacterial growth and did
      not die in response to the infection, compared with MON24. In contrast, MON24
      become Annexin V and Propidium iodide positive after 36 h of M. tuberculosis
      infection. Although, there were striking differences between MON24 and MDM120,
      there were also some differences in the response to the mycobacterial strains
      used. Finally, in MDM120 infected with M. tuberculosis H37Rv, a lower percentage
      of mycobacterial phagosomes accumulated transferrin and a higher percentage co
      localized with cathelicidin than in MON24. These results demonstrate that innate
      responses induced by M. tuberculosis depends upon the stage of differentiation of
      mononuclear phagocytes and support that terminally differentiated cells are more
      efficient anti-mycobacterial effectors than the less differentiated ones. 

PMID- 24566281
TI  - In vitro evaluation of the antiviral activity of the synthetic epigallocatechin
      gallate analog-epigallocatechin gallate (EGCG) palmitate against porcine
      reproductive and respiratory syndrome virus.
AB  - In this study, epigallocatechin gallate (EGCG) palmitate was synthesized and its
      anti-porcine reproductive and respiratory syndrome virus (PRRSV) activity was
      studied. Specifically, EGCG palmitate was evaluated for its ability to inhibit
      PRRSV infection in MARC-145 cells when administered as pre-, post-, or co
      treatment. EGCG and ribavirin were used as controls. The results showed that a
      50% cytotoxic concentration (CC50) of EGCG, EGCG palmitate, and ribavirin was
      achieved at 2,359.71, 431.42, and 94.06 MUM, respectively. All three drugs
      inhibited PRRSV in a dose-dependent manner regardless of the treatment protocol.
      EGCG palmitate exhibited higher cytotoxicity than EGCG, but lower cytotoxicity
      than ribavirin. EGCG palmitate anti-PRRSV activity was significantly higher than
      that of EGCG and ribavirin, both as pre-treatment and post-treatment. Under the
      former conditions and a tissue culture infectious dose of 10 and 100, the
      selectivity index (SI) of EGCG palmitate in the inhibition of PRRSV was 3.8 and
      2.9 times higher than that of ribavirin when administered as a pre-treatment,
      while the SI of EGCG palmitate in the inhibition of PRRSV was 3.0 and 1.9 times
      higher than ribavirin when administered as a post-treatment. Therefore, EGCG
      palmitate is potentially effective as an anti-PRRSV agent and thus of interest to
      the pharmaceutical industry. 

PMID- 24566284
TI  - Mycobacterium tuberculosis-specific polyfunctional cytotoxic CD8+ T cells express
      CD69.
AB  - Increasing evidences in animals and humans suggest that CD8(+) T cells contribute
      significantly to immune defenses against Mycobacterium tuberculosis (Mtb). In the
      present study, we found that without any stimulation, CD8(+) T cells in pleural
      fluid cells (PFCs) expressed significantly higher levels of CD69 than PBMCs from
      patients with tuberculous pleurisy (TBP). CD8(+)CD69(+) T cells expressed
      significantly higher levels of CD45RO and HLA-DR and lower levels of CD45RA than
      CD8(+)CD69(-) T cells, demonstrating that CD8(+)CD69(+) T cells were activated
      memory cells. Furthermore, we found higher expression of CCR6 and lower
      expression of CCR7 and CD62L on CD8(+)CD69(+) T cells compared with CD8(+)CD69(-)
      T cells, suggesting that the expression of CCR6 and reduced expression of CCR7
      and CD62L might facilitate the migration of circulating CD8(+)CD69(+) T cells
      into tuberculous pleural space. Importantly, following stimulation with culture
      filtrate protein of 10 kDa (CFP10) peptides, CD8(+)CD69(+) T cells but not
      CD8(+)CD69(-) T cells expressed CD107a/b, IFN-gamma and TNF-alpha, demonstrating
      that CD8(+)CD69(+) T cells were MTB-specific cells. In addition, the majority of
      CD8(+)CD69(+) T cells were dominated by polyfunctional T cells. In summary, we
      demonstrated that CD69 as a useful marker for MTB-specific CD8(+) T cells in PFCs
      from patients with TBP enabled a direct ex vivo estimation of the quantity, as
      well as the quality, of MTB-specific CD8(+) responses. 

PMID- 24566285
TI  - Molecular characterization of Mycobacterium tuberculosis isolates from elephants
      of Nepal.
AB  - Mycobacterium tuberculosis was cultured from the lung tissues of 3 captive
      elephants in Nepal that died with extensive lung lesions. Spoligotyping, TbD1
      detection and multi-locus variable number of tandem repeat analysis (MLVA)
      results suggested 3 isolates belonged to a specific lineage of Indo-Oceanic
      clade, EAI5 SIT 138. One of the elephant isolates had a new synonymous single
      nucleotide polymorphism (SNP) T231C in the gyrA sequence, and the same SNP was
      also found in human isolates in Nepal. MLVA results and transfer history of the
      elephants suggested that 2 of them might be infected with M. tuberculosis from
      the same source. These findings indicated the source of M. tuberculosis infection
      of those elephants were local residents, presumably their handlers. Further
      investigation including detailed genotyping of elephant and human isolates is
      needed to clarify the infection route and eventually prevent the transmission of
      tuberculosis to susceptible hosts. 

PMID- 24566286
TI  - Fluid mechanics relevant to flow through pretreatment of cellulosic biomass.
AB  - The present study investigates fluid mechanical properties of cellulosic
      feedstocks relevant to flow through (FT) pretreatment for biological conversion
      of cellulosic biomass. The results inform identifying conditions for which FT
      pretreatment can be implemented in a practical context. Measurements of pressure
      drop across packed beds, viscous compaction and water absorption are reported for
      milled and not milled sugarcane bagasse, switchgrass and poplar, and important
      factors impacting viscous flow are deduced. Using biomass knife-milled to pass
      through a 2mm sieve, the observed pressure drop was highest for bagasse,
      intermediate for switchgrass and lowest for poplar. The highest pressure drop was
      associated with the presence of more fine particles, greater viscous compaction
      and the degree of water absorption. Using bagasse without particle size
      reduction, the instability of the reactor during pretreatment above 140kg/m(3)
      sets an upper bound on the allowable concentration for continuous stable flow. 

PMID- 24566287
TI  - Characterization of microbial current production as a function of microbe
      electrode-interaction.
AB  - Microbe-electrode-interactions are keys for microbial fuel cell technology.
      Nevertheless, standard measurement routines to analyze the interplay of microbial
      physiology and material characteristics have not been introduced yet. In this
      study, graphite anodes with varying surface properties were evaluated using pure
      cultures of Shewanella oneidensis and Geobacter sulfurreducens, as well as
      defined and undefined mixed cultures. The evaluation routine consisted of a
      galvanostatic period, a current sweep and an evaluation of population density.
      The results show that surface area correlates only to a certain extent with
      population density and anode performance. Furthermore, the study highlights a
      strain-specific microbe-electrode-interaction, which is affected by the
      introduction of another microorganism. Moreover, evidence is provided for the
      possibility of translating results from pure culture to undefined mixed species
      experiments. This is the first study on microbe-electrode-interaction that
      systematically integrates and compares electrochemical and biological data. 

PMID- 24566289
TI  - Added value of dual-energy computed tomography versus single-energy computed
      tomography in assessing ferromagnetic properties of ballistic projectiles:
      implications for magnetic resonance imaging of gunshot victims.
AB  - OBJECTIVE: The objective of this study was to assess the discriminative power of
      dual-energy computed tomography (DECT) versus single-energy CT (SECT) to
      distinguish between ferromagnetic and non-ferromagnetic ballistic projectiles to
      improve safety regarding magnetic resonance (MR) imaging studies in patients with
      retained projectiles. MATERIALS AND METHODS: Twenty-seven ballistic projectiles
      including 25 bullets (diameter, 3-15 mm) and 2 shotgun pellets (2 mm each) were
      examined in an anthropomorphic chest phantom using 128-section dual-source CT.
      Data acquisition was performed with tube voltages set at 80, 100, 120, and 140
      kV(p). Two readers independently assessed CT numbers of the projectile's core on
      images reconstructed with an extended CT scale. Dual-energy indices (DEIs) were
      calculated from both 80-/140-kV(p) and 100-/140-kV(p) pairs; receiver operating
      characteristics curves were fitted to assess ferromagnetic properties by means of
      CT numbers and DEI. RESULTS: Nine (33%) of the projectiles were ferromagnetic; 18
      were nonferromagnetic (67%). Interreader and intrareader correlations of CT
      number measurements were excellent (intraclass correlation coefficients, >0.906;
      P<0.001). The DEI calculated from both 80/140 and 100/140 kV(p) were
      significantly (P<0.05) different between the ferromagnetic and non-ferromagnetic
      projectiles. The area under the curve (AUC) was 0.75 and 0.8 for the tube voltage
      pairs of 80/140 and 100/140 kV(p) (P<0.05; 95% confidence interval, 0.57-0.94 and
      0.62-0.97, respectively) to differentiate between the ferromagnetic and non
      ferromagnetic ballistic projectiles; which increased to 0.83 and 0.85 when
      shotgun pellets were excluded from the analysis. The AUC for SECT was 0.69 and
      0.73 (80 and 100 kV[p], respectively). CONCLUSIONS: Measurements of DECT combined
      with an extended CT scale allow for the discrimination of projectiles with non
      ferromagnetic from those with ferromagnetic properties in an anthropomorphic
      chest phantom with a higher AUC compared with SECT. This study indicates that
      DECT may have the potential to contribute to MR safety and allow for MR imaging
      of patients with retained projectiles. However, further studies are necessary
      before this concept may be used to triage clinical patients before MR.

PMID- 24566290
TI  - High permittivity dielectric pads improve high spatial resolution magnetic
      resonance imaging of the inner ear at 7 T.
AB  - OBJECTIVES: The objective of this study was to evaluate the use of dielectric
      pads for improving high spatial resolution imaging of the inner ear at 7 T.
      MATERIALS AND METHODS: Two sets of dielectric pads were designed using
      electromagnetic simulations and implemented using a deuterated suspension of
      barium titanate. Their effect on transmit efficiency, contrast homogeneity, and
      diagnostic image quality was evaluated in vivo (N = 10). In addition, their
      effect on the specific absorption rate was evaluated numerically. RESULTS:
      Statistically significant improvements (P < 0.001) in several measures of the
      image quality were obtained by using dielectric pads. The dielectric pads lead to
      an increase in the transmit efficiency and uniformity at the location of the
      inner ear, which is reflected in both an increased contrast homogeneity and an
      increased diagnostic value. Simulations show that the dielectric pads do not
      increase the peak local specific absorption rate. CONCLUSIONS: Using
      geometrically tailored dielectric pads enables high spatial resolution magnetic
      resonance imaging of the human inner ear at 7 T. The high spatial resolution
      improves the depiction of the fine inner ear structures, showing the benefit of
      magnetic resonance imaging at ultrahigh fields.

PMID- 24566288
TI  - Evaluation of intrarenal oxygenation in iodinated contrast-induced acute kidney
      injury-susceptible rats by blood oxygen level-dependent magnetic resonance
      imaging.
AB  - OBJECTIVES: The objectives of this study were to evaluate differences in
      intrarenal oxygenation as assessed by blood oxygen level-dependent (BOLD)
      magnetic resonance imaging in contrast-induced acute kidney injury (CIAKI)
      susceptible rats when using 4 contrast media with different physicochemical
      properties and to demonstrate the feasibility of acquiring urinary neutrophil
      gelatinase-associated lipocalin (NGAL) levels as a marker of CIAKI in this model.
      MATERIALS AND METHODS: Our institutional animal care and use committee approved
      the study. Sixty-six Sprague-Dawley rats were divided into CIAKI-susceptible
      groups (received nitric oxide synthase inhibitor N-nitro-L-arginine methyl ester
      [10 mg/kg] and cycloxygenase inhibitor indomethacin [10mg/kg]) and control groups
      (received saline instead). One of the 4 iodinated contrast agents (iothalamate,
      iohexol, ioxaglate, or iodixanol) was then administered (1600-mg organic iodine
      per kilogram of body weight). Multiple blood oxygen level-dependent magnetic
      resonance images were acquired on a Siemens 3.0-T scanner using a multiple
      gradient recalled echo sequence at baseline, after N-nitro-L-arginine methyl
      ester (or saline), indomethacin (or saline), and iodinated contrast agent (or
      placebo). R2* (R2*=1/T2*) maps were generated inline on the scanner. A mixed
      effects growth curve model with first-order autoregressive variance-covariance
      was used to analyze the temporal data. Urinary NGAL, a marker of kidney injury
      (unlike serum creatinine), was measured 4 hours after contrast injection in the 2
      subgroups. RESULTS: Differences in blood oxygen level-dependent magnetic
      resonance imaging results between the contrast media were observed in all 4 renal
      regions. However, the inner stripe of the outer medulla (ISOM) showed the most
      pronounced changes in the CIAKI-susceptible group and R2* increased significantly
      (P<0.01) over time with all 4 contrast media. In the control groups, only
      iodixanol showed an increase in R2* (P<0.05) over time. There was an agreement
      between increases in NGAL and R2* values in ISOM. CONCLUSIONS: In rats
      susceptible to CIAKI, those receiving contrast media had significant increases in
      R2* in renal ISOM compared with those receiving placebo. The agreement between
      NGAL and R2* values in the ISOM suggests that the observed immediate increase in
      R2* after contrast injection may be the earliest biomarker of renal injury.
      Further studies are necessary to establish threshold values of R2* associated
      with acute kidney injury and address the specificity of R2* to renal oxygenation
      status.

PMID- 24566291
TI  - Optimization of magnetization-prepared 3-dimensional fluid attenuated inversion
      recovery imaging for lesion detection at 7 T.
AB  - PURPOSE: The aim of this study was to optimize the 3-dimensional (3D) fluid
      attenuated inversion recovery (FLAIR) pulse sequence for isotropic high-spatial
      resolution imaging of white matter (WM) and cortical lesions at 7 T. MATERIALS
      AND METHODS: We added a magnetization-prepared (MP) FLAIR module to a Cube 3D
      fast spin echo sequence and optimized the refocusing flip angle train using
      extended phase graph simulations, taking into account image contrast, specific
      absorption rate (SAR), and signal-to-noise ratio (SNR) as well as T1/T2 values of
      the different species of interest (WM, grey matter, lesions) at 7 T. We also
      effected improved preparation homogeneity at 7 T by redesigning the refocusing
      pulse used in the MP segments. Two sets of refocusing flip angle trains-(a) an
      SNR-optimal and (b) a contrast-optimal set-were derived and used to scan 7
      patients with Alzheimer disease/cognitive impairment and 7 patients with multiple
      sclerosis. Conventional constant refocusing flip MP-FLAIR images were also
      acquired for comparison. Lesion SNR, contrast, and lesion count were compared
      between the 2 optimized and the standard FLAIR sequences. RESULTS: Whole brain
      coverage with 0.8 mm isotropic spatial resolution in ~5-minute scan times was
      achieved using the optimized 3D FLAIR sequences at clinically acceptable SAR
      levels. The SNR efficiency of the SNR-optimal sequence was significantly better
      than that of conventional constant refocusing flip MP-FLAIR sequence, whereas the
      scan time was reduced more than 2-fold (~5 vs >10 minutes). The contrast
      efficiency of the contrast-optimal sequence was comparable with that of the
      constant refocusing flip sequence. Lesion load ascertained by lesion counting was
      not significantly different among the sequences. CONCLUSION: Magnetization
      prepared FLAIR-Cube with refocusing flip angle trains optimized for SNR and
      contrast can be used to characterize WM and cortical lesions at 7 T with 0.8 mm
      isotropic resolution in short scan times and without SAR penalty.

PMID- 24566293
TI  - Instrumental assessment of halitosis for the general dental practitioner.
AB  - At the moment there are no clear protocols for the assessment of bad breath. An
      organoleptic evaluation is still the reference. To date there are several tools
      available to detect and quantify specific compounds related to halitosis. This
      paper reviews the available information on three sulphur monitors (OralChromaTM
      (CHM-1), Halimeter(r) and Breathtron(r)), in order to suggest guidance for the
      general dental practitioner. All three devices showed an acceptable correlation
      with organoleptic scores. The Halimeter(r) and Breathtron(r) seem the most
      appropriate devices for a general dental practitioner, because they are easy to
      handle. Because of its capacity of distinguishing between different sulphur
      compounds and due to its time-consuming and complicated use, the OralChromaTM
      (CHM-1) seems more suitable in a research environment. 

PMID- 24566294
TI  - Is the consistency more important than the ingredients for steroid treatment in
      eosinophilic esophagitis?

PMID- 24566292
TI  - Improved diagnostic accuracy with multiparametric magnetic resonance imaging of
      the breast using dynamic contrast-enhanced magnetic resonance imaging, diffusion
      weighted imaging, and 3-dimensional proton magnetic resonance spectroscopic
      imaging.
AB  - INTRODUCTION: The purpose of this study was to compare the diagnostic accuracy of
      dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) as a single
      parameter to multiparametric (MP) MRI with 2 (DCE MRI and diffusion-weighted
      imaging [DWI]) and 3 (DCE MRI, DWI, and 3-dimensional proton magnetic resonance
      spectroscopic imaging [3D H-MRSI]) parameters in breast cancer diagnosis.
      MATERIALS AND METHODS: This prospective study was approved by the institutional
      review board. Written informed consent was obtained in all patients. One hundred
      thirteen female patients (mean age, 52 years; range, 22-86 years) with an imaging
      abnormality (Breast Imaging Reporting and Data System 0, 4-5) were included in
      this study. Multiparametric MRI of the breast at 3 T with DCE MRI, DWI, and 3D H
      MRSI was performed. The likelihood of malignancy was assessed for DCE MRI and MP
      MRI with 2 (DCE MRI and DWI) and 3 (DCE MRI, DWI, and 3D H-MRSI) parameters
      separately. Histopathology was used as the standard of reference. Appropriate
      statistical tests were used to assess sensitivity, specificity, and diagnostic
      accuracy for each assessment combination. RESULTS: There were 74 malignant and 39
      benign breast lesions. Multiparametric MRI with 3 MRI parameters yielded
      significantly higher areas under the curve (0.936) in comparison with DCE MRI
      alone (0.814) (P<0.001). Multiparametric MRI with just 2 parameters at 3 T did
      not yield higher areas under the curve (0.808) than did DCE MRI alone (0.814).
      Multiparametric MRI with 3 parameters resulted in elimination of false-negative
      lesions and significantly reduced the false-positives ones (P=0.002).
      CONCLUSIONS: Multiparametric MRI with 3 parameters increases the diagnostic
      accuracy of breast cancer in comparison with DCE-MRI alone and MP MRI with 2
      parameters.

PMID- 24566296
TI  - Permanganate diffusion and reaction in sedimentary rocks.
AB  - In situ chemical oxidation using permanganate has frequently been used to treat
      chlorinated solvents in fractured bedrock aquifers. However, in systems where
      matrix back-diffusion is an important process, the ability of the oxidant to
      migrate and treat target contaminants within the rock matrix will likely
      determine the overall effectiveness of this remedial approach. In this study, a
      series of diffusion experiments were performed to measure the permanganate
      diffusion and reaction in four different types of sedimentary rocks (dark gray
      mudstone, light gray mudstone, red sandstone, and tan sandstone). Results showed
      that, within the experimental time frame (~2 months), oxidant migration into the
      rock was limited to distances less than 500 MUm. The observed diffusivities for
      permanganate into the rock matrices ranged from 5.3 * 10(-13) to 1.3 * 10(-11)
      cm(2)/s. These values were reasonably predicted by accounting for both the rock
      oxidant demand and the effective diffusivity of the rock. Various Mn minerals
      formed as surface coatings from reduction of permanganate coupled with oxidation
      of total organic carbon (TOC), and the nature of the formed Mn minerals was
      dependent upon the rock type. Post-treatment tracer testing showed that these Mn
      mineral coatings had a negligible impact on diffusion through the rock. Overall,
      our results showed that the extent of permanganate diffusion and reaction
      depended on rock properties, including porosity, mineralogy, and organic carbon.
      These results have important implications for our understanding of long-term
      organic contaminant remediation in sedimentary rocks using permanganate.

PMID- 24566298
TI  - Scholarship and zeitgeist.

PMID- 24566297
TI  - Fibromyalgia.

PMID- 24566299
TI  - What can ICD-11 be that DSM-5 cannot?

PMID- 24566295
TI  - Eosinophilic esophagitis.
AB  - OBJECTIVE: To review the understanding of the pathogenesis of eosinophilic
      esophagitis (EoE) and the role of the immune system in the disease process. DATA
      SOURCES: Peer-reviewed articles on EoE from PubMed searching for "Eosinophilic
      Esophagitis and fibrosis" in the period of 1995 to 2013. STUDY SELECTIONS:
      Studies on the clinical and immunologic features, pathogenesis, and management of
      EoE. RESULTS: Recent work has revealed that thymic stromal lymphopoietin and
      basophil have an increased role in the pathogenesis of disease. Additional
      understanding on the role of fibrosis in EoE is emerging. CONCLUSION: The
      incidence of EoE is increasing like most atopic disease. Similar to other
      allergic diseases, EoE is treated with topical steroids and/or allergen
      avoidance.

PMID- 24566300
TI  - Effects of platelet-rich plasma on wrinkles and skin tone in Asian lower eyelid
      skin: preliminary results from a prospective, randomised, split-face trial.

PMID- 24566301
TI  - Two new bidesmoside triterpenoid saponins from the seeds of Momordica charantia
      L.
AB  - Two new bidesmoside triterpenoid saponins which were identifed as 28-O-beta-D
      xylopyranosyl(1->3)-beta-D-xylopyranosyl(1->4)-alpha-L-rhamnopyranosyl(1->2)
      [alpha-L-rhamno-pyranosyl(1->3)]-beta-D-fucopyranosyl gypsogenin 3-O-beta-D
      glucopyranosyl (1->2)-beta-D-glucopyranosiduronic acid (C1) and 28-O-beta-D
      xylopyranosyl(1->4)-alpha-L-rhamnopyranosyl (1->2)-[alpha-L-rhamnopyranosyl(1
      >3)]-beta-D-fucopyranosyl gypsogenin 3-O-beta-D-gluco-pyranosyl(1->2)-beta-D
      glucopyranosiduronic acid (C2) were isolated together with two known compounds
      from the seeds of Momordica charantia L. Their structures were elucidated by the
      combination of mass spectrometry (MS), one and two-dimensional NMR experiments
      and chemical reactions. 

PMID- 24566302
TI  - In silico studies of quinoxaline-2-carboxamide 1,4-di-n-oxide derivatives as
      antimycobacterial agents.
AB  - Molecular modelling studies were performed on some previously reported novel
      quinoxaline-2-carboxamide 1,4-di-N-oxide derivatives (series 1-9). Using the
      LigandScout program, a pharmacophore model was developed to further optimize the
      antimycobacterial activity of this series of compounds. Using the Dock6 program,
      docking studies were performed in order to investigate the mode of binding of
      these compounds. The molecular modeling study allowed us to confirm the
      preferential binding mode of these quinoxaline-2-carboxamide 1,4-di-N-oxide
      derivatives inside the active site. The obtained binding mode was as same as that
      of the novobiocin X-ray structure. 

PMID- 24566303
TI  - On tuning the fluorescence emission of porphyrin free bases bonded to the pore
      walls of organo-modified silica.
AB  - A sol-gel methodology has been duly developed in order to perform a controlled
      covalent coupling of tetrapyrrole macrocycles (e.g., porphyrins, phthalocyanines,
      naphthalocyanines, chlorophyll, etc.) to the pores of metal oxide networks. The
      resulting absorption and emission spectra intensities in the UV-VIS-NIR range
      have been found to depend on the polarity existing inside the pores of the
      network; in turn, this polarization can be tuned through the attachment of
      organic substituents to the tetrapyrrrole macrocycles before bonding them to the
      pore network. The paper shows clear evidence of the real possibility of
      maximizing fluorescence emissions from metal-free bases of substituted
      tetraphenylporphyrins, especially when these molecules are bonded to the walls of
      functionalized silica surfaces via the attachment of alkyl or aryl groups arising
      from the addition of organo-modified alkoxides. 

PMID- 24566304
TI  - Addition of bases to the 5'-end of human telomeric DNA: influences on thermal
      stability and energetics of unfolding.
AB  - Telomeric DNA has been intensely investigated for its role in chromosome
      protection, aging, cell death, and disease. In humans the telomeric tandem repeat
      (TTAGGG)n is found at the ends of chromosomes and provides a novel target for the
      development of new drugs in the treatment of age related diseases such as cancer.
      These telomeric sequences show slight sequence variations from species to
      species; however, each contains repeats of 3 to 4 guanines allowing the G-rich
      strands to fold into compact and stable nuclease resistant conformations referred
      to as G-quadruplexes. The focus of this manuscript is to examine the effects of
      5'-nucleotides flanking the human telomeric core sequence 5'-AGGG(TTAGGG) 3-3' (h
      Tel22). Our studies reveal that the addition of the 5'-flanking nucleotides (5'
      T, and 5'-TT) results in significant changes to the thermodynamic stability of
      the G-quadruplex structure. Our data indicate that the observed changes in
      stability are associated with changes in the number of bound waters resulting
      from the addition of 5'-flanking nucleotides to the h-Tel22 sequence as well as
      possible intermolecular interactions of the 5' overhang with the core structure. 

PMID- 24566305
TI  - Carnosinases, their substrates and diseases.
AB  - Carnosinases are Xaa-His dipeptidases that play diverse functions throughout all
      kingdoms of life. Human isoforms of carnosinase (CN1 and CN2) under appropriate
      conditions catalyze the hydrolysis of the dipeptides carnosine (beta-alanyl-L
      histidine) and homocarnosine (gamma-aminobutyryl-L-histidine). Alterations of
      serum carnosinase (CN1) activity has been associated with several pathological
      conditions, such as neurological disorders, chronic diseases and cancer. For this
      reason the use of carnosinase levels as a biomarker in cerebrospinal fluid (CSF)
      has been questioned. The hydrolysis of imidazole-related dipeptides in
      prokaryotes and eukaryotes is also catalyzed by aminoacyl-histidine dipeptidases
      like PepD (EC 3.4.13.3), PepV (EC 3.4.13.19) and anserinase (EC 3.4.13.5). The
      review deals with the structure and function of this class of enzymes in
      physiological and pathological conditions. The main substrates of these enzymes,
      i.e., carnosine, homocarnosine and anserine (beta-alanyl-3-methyl-L-histidine)
      will also be described. 

PMID- 24566306
TI  - Fatty acids from pool lipids as possible precursors of the male marking pheromone
      in bumblebees.
AB  - Triacylglycerols (TGs) stored in the fat bodies of bumblebee males have a species
      specific composition. The striking structural similarities between TG fatty acids
      (FAs) and components of the male marking pheromone in certain species led to the
      hypothesis that FAs may serve as precursors in pheromone biosynthesis. Here, we
      analysed TGs from B. ruderatus, B. bohemicus, and B. campestris. Nonadec-9-ene
      and icos-15-en-1-ol are the main components of B. ruderatus labial gland
      secretion, forming up to 92% of the gland extract. The corresponding icos-11-enic
      and icos-15-enic acids were found in TGs at levels higher than usual for
      bumblebee species. We found similar relationships in B. campestris and B.
      bohemicus. These results suggest that FAs might be precursors of aliphatic
      compounds in the male pheromones. Furthermore, we report for the first time the
      pheromone structure of B. ruderatus males. 

PMID- 24566307
TI  - Influence of extractive solvents on lipid and fatty acids content of edible
      freshwater algal and seaweed products, the green Microalga Chlorella kessleri and
      the Cyanobacterium Spirulina platensis.
AB  - Total lipid contents of green (Chlorella pyrenoidosa, C), red (Porphyra tenera,
      N; Palmaria palmata, D), and brown (Laminaria japonica, K; Eisenia bicyclis, A;
      Undaria pinnatifida, W, WI; Hizikia fusiformis, H) commercial edible algal and
      cyanobacterial (Spirulina platensis, S) products, and autotrophically cultivated
      samples of the green microalga Chlorella kessleri (CK) and the cyanobacterium
      Spirulina platensis (SP) were determined using a solvent mixture of
      methanol/chloroform/water (1:2:1, v/v/v, solvent I) and n-hexane (solvent II).
      Total lipid contents ranged from 0.64% (II) to 18.02% (I) by dry weight and the
      highest total lipid content was observed in the autotrophically cultivated
      cyanobacterium Spirulina platensis. Solvent mixture I was found to be more
      effective than solvent II. Fatty acids were determined by gas chromatography of
      their methyl esters (% of total FAMEs). Generally, the predominant fatty acids
      (all results for extractions with solvent mixture I) were saturated palmitic acid
      (C16:0; 24.64%-65.49%), monounsaturated oleic acid (C18:1(n-9); 2.79%-26.45%),
      polyunsaturated linoleic acid (C18:2(n-6); 0.71%-36.38%), alpha-linolenic acid
      (C18:3(n-3); 0.00%-21.29%), gamma-linolenic acid (C18:3(n-6); 1.94%-17.36%), and
      arachidonic acid (C20:4(n-6); 0.00%-15.37%). The highest content of omega-3 fatty
      acids (21.29%) was determined in Chlorella pyrenoidosa using solvent I, while
      conversely, the highest content of omega-6 fatty acids (41.42%) was observed in
      Chlorella kessleri using the same solvent. 

PMID- 24566308
TI  - Edge-termination and core-modification effects of hexagonal nanosheet graphene.
AB  - Optimized geometries and electronic structures of two different hexagonal
      grapheme nanosheets (HGNSs), with armchair (n-A-HGNS, n = 3-11) and zigzag (n-Z
      HGNS, n = 1-8) edges have been calculated by using the GGA/PBE method implemented
      in the SIESTA package, with the DZP basis set, where n represents the number of
      peripheral rings. The computed HOMO-LUMO energy gap (Eg = ELUMO - EHOMO)
      decreases for fully H-terminated A- and Z-HGNSs with increasing n, i.e., with
      increasing nanosheet size and ppi-orbitals being widely delocalized over the
      sheet surface. The full terminations, calculated with various functional groups,
      including the electron-withdrawing (F-, Cl-, and CN-) and -donating (OH-, and SH
      ) substitutions, were addressed. Significant lowering of EHOMO and ELUMO was
      obtained for CN-terminated HGNS as compared to those for H-terminated ones due to
      the mesomeric effect. The calculated Eg value decreases with increasing n for all
      terminations, whereby for the SH-termination in HGNS, the termination effect
      becomes less significant with increasing n. Further, the calculation results for
      stabilities of HGNS oxides support the tendency toward the oxidative reactivity
      at the edge site of the sheet, which shows most pronounced C-C bond length
      alternation, by chemical modification. Physical properties of HGNSs with various
      numbers of the core-defects, which can be obtained by strong oxidation, were also
      investigated. Their structures can change drastically from planar to saddle-like
      shapes. These conformations could be used as stationary phases with controlled
      interaction in the separation methods such as HPLC and the other chemical
      analysis techniques. 

PMID- 24566309
TI  - Functional properties of a cysteine proteinase from pineapple fruit with improved
      resistance to fungal pathogens in Arabidopsis thaliana.
AB  - In plant cells, many cysteine proteinases (CPs) are synthesized as precursors in
      the endoplasmic reticulum, and then are subject to post-translational
      modifications to form the active mature proteinases. They participate in various
      cellular and physiological functions. Here, AcCP2, a CP from pineapple fruit
      (Ananas comosus L.) belonging to the C1A subfamily is analyzed based on the
      molecular modeling and homology alignment. Transcripts of AcCP2 can be detected
      in the different parts of fruits (particularly outer sarcocarps), and gradually
      increased during fruit development until maturity. To analyze the substrate
      specificity of AcCP2, the recombinant protein was overexpressed and purified from
      Pichia pastoris. The precursor of purified AcCP2 can be processed to a 25 kDa
      active form after acid treatment (pH 4.3). Its optimum proteolytic activity to Bz
      Phe-Val-Arg-NH-Mec is at neutral pH. In addition, the overexpression of AcCP2
      gene in Arabidopsis thaliana can improve the resistance to fungal pathogen of
      Botrytis cinerea. These data indicate that AcCP2 is a multifunctional proteinase,
      and its expression could cause fruit developmental characteristics of pineapple
      and resistance responses in transgenic Arabidopsis plants. 

PMID- 24566311
TI  - Ultrafast internal conversion of aromatic molecules studied by photoelectron
      spectroscopy using Sub-20 fs laser pulses.
AB  - This article describes our recent experimental studies on internal conversion via
      a conical intersection using photoelectron spectroscopy. Ultrafast S2(pipi*)
      S1(npi*) internal conversion in pyrazine is observed in real time using sub-20 fs
      deep ultraviolet pulses (264 and 198 nm). While the photoelectron kinetic energy
      distribution does not exhibit a clear signature of internal conversion, the
      photoelectron angular anisotropy unambiguously reveals the sudden change of
      electron configuration upon internal conversion. An explanation is presented as
      to why these two observables have different sensitivities to internal conversion.
      The 198 nm probe photon energy is insufficient for covering the entire Franck
      Condon envelopes upon photoionization from S2/S1 to D1/D0. A vacuum ultraviolet
      free electron laser (SCSS) producing 161 nm radiation is employed to solve this
      problem, while its pulse-to-pulse timing jitter limits the time resolution to
      about 1 ps. The S2-S1 internal conversion is revisited using the sub-20 fs 159 nm
      pulse created by filamentation four-wave mixing. Conical intersections between
      D1(pi-1) and D0(n-1) and also between the Rydberg state with a D1 ion core and
      that with a D0 ion core of pyrazine are studied by He(I) photoelectron
      spectroscopy, pulsed field ionization photoelectron spectroscopy and one-color
      resonance-enhanced multiphoton ionization spectroscopy. Finally, ultrafast
      S2(pipi*)-S1(pipi*) internal conversion in benzene and toluene are compared with
      pyrazine. 

PMID- 24566310
TI  - Endotoxin molecule lipopolysaccharide-induced zebrafish inflammation model: a
      novel screening method for anti-inflammatory drugs.
AB  - Lipopolysaccharide (LPS), an endotoxin molecule, has been used to induce
      inflammatory responses. In this study, LPS was used to establish an in vivo
      inflammation model in zebrafish for drug screening. We present an experimental
      method that conveniently and rapidly assesses the anti-inflammatory properties of
      drugs. The yolks of 3-day post-fertilization (dpf) larvae were injected with 0.5
      mg/mL LPS to induce fatal inflammation. After LPS stimulation, macrophages were
      tracked by NR and SB staining and neutrophil migration was observed using the
      MPO:GFP line. Larval mortality was used as the primary end-point. Expression
      levels of key cytokines involved in the inflammatory response including IL-1beta,
      IL-6, and TNF-alpha, were measured using quantitative reverse transcription
      polymerase chain reaction (RT-PCR). Macrophages and neutrophils were both
      recruited to the LPS-injected site during the inflammatory response. Mortality
      was increased by LPS in a dose-dependent manner within 48 h. Analyses of IL
      1beta, IL-6, and TNF-alpha expression levels revealed the upregulation of the
      inflammatory response in the LPS-injected larvae. Further, the anti-inflammatory
      activity of chlorogenic acid (CA) was evaluated in this zebrafish model to screen
      for anti-inflammatory drugs. A preliminary result showed that CA revealed a
      similar effect as the corticosteroid dexamethasone (DEX), which was used as a
      positive control, by inhibiting macrophage and neutrophil recruitment to the LPS
      site and improving survival. Our results suggest that this zebrafish screening
      model could be applied to study inflammation-mediated diseases. Moreover, the
      Traditional Chinese Medicine CA displays potential anti-inflammatory activity. 

PMID- 24566312
TI  - A tractable and efficient one-pot synthesis of 5'-Azido-5'-deoxyribonucleosides.
AB  - Synthetic routes to 5'-azidoribonucleosides are reported for adenosine, cytidine,
      guanosine, and uridine, resulting in a widely applicable one-pot methodology for
      the synthesis of these and related compounds. The target compounds are
      appropriate as precursors in a variety of purposive syntheses, as the synthetic
      and therapeutic relevance of azido- and amino-modified nucleosides is expansive.
      Furthermore, in the conversion of alcohols to azides, these methods offer a
      tractable alternative to the Mitsunobu and other more difficult reactions. 

PMID- 24566313
TI  - Preparation and in vitro evaluation of glycyrrhetinic acid-modified curcumin
      loaded nanostructured lipid carriers.
AB  - Curcumin, a phenolic antioxidant compound derived from the rhizome of the
      turmeric plant Curcuma longa, has proven to be a modulator of intracellular
      signaling pathways that control cancer cell growth, inflammation, invasion and
      apoptosis, revealing its anticancer potential. In this study, a Glycyrrhetinic
      Acid-Modified Curcumin-Loaded Nanostructured Lipid Carrier (Cur-GA-PEG-NLC) was
      prepared by the film ultrasound method to improve the tumor-targeting ability.
      The drug content was detected by an UV spectrophotometry method. The
      encapsulation efficiency of curcumin in the nanostructured lipid carriers (NLCs)
      was determined using a mini-column centrifugation method. The encapsulation
      efficiency for various Cur-GA-PEG-NLC was within the range of 90.06%-95.31% and
      particle size was between 123.1 nm and 132.7 nm. An in vitro MTT assay showed
      that Cur-GA10%-PEG-NLC had significantly high cellular uptake and cytotoxicity
      against HepG2 cells compared with other groups. 

PMID- 24566314
TI  - Clinical application of microRNA testing in neuroendocrine tumors of the
      gastrointestinal tract.
AB  - It is well documented that dysregulation of microRNAs is a hallmark of human
      cancers. Thus, this family of small non-coding regulatory molecules represents an
      excellent source of sensitive biomarkers. Unique microRNAs expression profiles
      have been associated with different types and subsets of gastrointestinal tumors
      including gastroenteropancreatic neuroendocrine tumors (GEP-NETs). GEP-NETs are a
      heterogeneous group of epithelial neoplasms with neuroendocrine differentiation.
      At present, early detection and surgical resection of GEP-NETs represent the best
      chance for a cure. Thus, clinically useful biomarkers for GEP-NETs that strongly
      correlate with early detection are urgently needed. The purpose of this review is
      to summarize the role of miRNAs in GEP-NET carcinogenesis and their possible use
      as novel diagnostic, prognostic and predictive biomarkers. 

PMID- 24566315
TI  - Novel lycorine derivatives as anticancer agents: synthesis and in vitro
      biological evaluation.
AB  - Lycorine, which is the most abundant alkaloid isolated from the Amaryllidaceae
      family of plants, reportedly exhibits promising anticancer activities. Herein, a
      series of novel lycorine derivatives were synthesized and evaluated for their in
      vitro inhibitory activities against seven different cancer cell lines, including
      A549, HCT116, SK-OV-3, NCI-H460, K562, MCF-7 and HL-60. The results indicated
      that compounds bearing diverse amine substituents at the C-2 position
      demonstrated good anticancer activities. The selectivity towards different cancer
      cell lines of the synthesized derivatives is discussed. 

PMID- 24566316
TI  - Pharmacophore generation from a drug-like core molecule surrounded by a library
      peptide via the 10BASEd-T on bacteriophage T7.
AB  - We have achieved site-specific conjugation of several haloacetamide derivatives
      into designated cysteines on bacteriophage T7-displayed peptides, which are fused
      to T7 capsid protein gp10. This easiest gp10 based-thioetherification (10BASEd-T)
      undergoes almost quantitatively like a click reaction without side reaction or
      loss of phage infectivity. The post-translational modification yield, as well as
      the site-specificity, is quantitatively analyzed by a fluorescent densitometric
      analysis after gel electrophoresis. The detailed structure of the modified
      peptide on phage is identified with tandem mass spectrometry. Construction of
      such a peptide-fused phage library possessing non-natural core structures will be
      useful for future drug discovery. For this aim, we propose a novel concept of
      pharmacophore generation from a drug-like molecule (i.e., salicylic acid)
      conjugated with surrounding randomized peptides. By using the hybrid library,
      streptavidin-specific binders are isolated through four rounds of biopanning. 

PMID- 24566317
TI  - Effects of honey and its mechanisms of action on the development and progression
      of cancer.
AB  - Honey is a natural product known for its varied biological or pharmacological
      activities-ranging from anti-inflammatory, antioxidant, antibacterial,
      antihypertensive to hypoglycemic effects. This review article focuses on the role
      of honey in modulating the development and progression of tumors or cancers. It
      reviews available evidence (some of which is very recent) with regards to the
      antimetastatic, antiproliferative and anticancer effects of honey in various
      forms of cancer. These effects of honey have been thoroughly investigated in
      certain cancers such as breast, liver and colorectal cancer cell lines. In
      contrast, limited but promising data are available for other forms of cancers
      including prostate, bladder, endometrial, kidney, skin, cervical, oral and bone
      cancer cells. The article also underscores the various possible mechanisms by
      which honey may inhibit growth and proliferation of tumors or cancers. These
      include regulation of cell cycle, activation of mitochondrial pathway, induction
      of mitochondrial outer membrane permeabilization, induction of apoptosis,
      modulation of oxidative stress, amelioration of inflammation, modulation of
      insulin signaling and inhibition of angiogenesis. Honey is highly cytotoxic
      against tumor or cancer cells while it is non-cytotoxic to normal cells. The data
      indicate that honey can inhibit carcinogenesis by modulating the molecular
      processes of initiation, promotion, and progression stages. Thus, it may serve as
      a potential and promising anticancer agent which warrants further experimental
      and clinical studies. 

PMID- 24566318
TI  - Synthesis and antiproliferative activity of some novel triazole derivatives from
      dehydroabietic acid.
AB  - Dehydroabietic acid (DHA) is a naturally occurring diterpene with different and
      relevant biological activities. Previous studies have shown that some DHA
      derivatives display antiproliferative activity. However, the reported compounds
      did not include triazole derivatives. Starting from DHA (8,11,13-abietatrien-18
      oic acid), and its alcohol dehydroabietinol (8,11,13-abietatrien-18-ol), four
      alkyl esters were prepared. The alkyl terpenes were treated with different
      aromatic azides to synthesize hybrid compounds using click chemistry. Some 16 new
      DHA hybrids were thus synthesized and their structures were confirmed by
      spectroscopic and spectrometric means. The antiproliferative activity of the new
      compounds was assessed towards human cell lines, namely normal lung fibroblasts
      (MRC-5), gastric epithelial adenocarcinoma (AGS), lung cancer (SK-MES-1) and
      bladder carcinoma (J82) cells. Better antiproliferative effect was found for
      compound 5, with an IC50 of 6.1 MUM and selectivity on SK-MES-1 cells. Under the
      same experimental conditions, the IC50 of etoposide, was 1.83 uM. 

PMID- 24566319
TI  - Skullcap (Scutellaria baicalensis) extract and its active compound, wogonin,
      inhibit ovalbumin-induced Th2-mediated response.
AB  - Skullcap (Scutellaria baicalensis) has been widely used as a dietary ingredient
      and traditional herbal medicine owing to its anti-inflammatory and anticancer
      properties. In this study, we investigated the anti-allergic effects of skullcap
      and its active compounds, focusing on T cell-mediated responses ex vivo and in
      vivo. Splenocytes from mice sensitized with ovalbumin (OVA) were isolated for
      analyses of cytokine production and cell viability. Mice sensitized with OVA were
      orally administered skullcap or wogonin for 16 days, and then immunoglobulin (Ig)
      and cytokine levels were measured by enzyme-linked immunosorbent assays.
      Treatment with skullcap significantly inhibited interleukin (IL)-4 production
      without reduction of cell viability. Moreover, wogonin, but not baicalin and
      baicalein, suppressed IL-4 and interferon-gamma production. In vivo, skullcap and
      wogonin downregulated OVA-induced Th2 immune responses, especially IgE and IL-5
      prediction. Wogonin as an active component of skullcap may be applied as a
      therapeutic agent for IgE- and IL-5-mediated allergic disorders. 

PMID- 24566320
TI  - In vivo and in vitro anti-tumor effects of fungal extracts.
AB  - Fungal extracts are extensively used as nutritional supplements in Far-Eastern
      Asia. In this study, we aimed to evaluate the anti-cancer activities of some
      different fungal species against different cancer cell lines. The water or
      ethanol extracts of Fomitopsis pinicola (F. pinicola), Ganoderma sinense,
      Fomitopsis officinalis, Polyporus melanopus, and Taiwanofungus camphorates were
      used to evaluate the anti-cancer activities in various cancer cells. We found
      that all of the fungi ethanol extracts used in this study exert anti-cancer
      activities in vitro, whereas water extracts show lower inhibitory activities as
      determined by 3-(4,5-methylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays.
      Among the tested fungi species, F. pinicola ethanol extract exerts the most
      significant anti-cancer activity (growth inhibitory ratio 82.8%, p < 0.001) by
      increasing cell apoptosis. Moreover, F. pinicola ethanol extract significantly
      decreased tumor size (tumor growth inhibitory ratio 54%, p < 0.05) and increased
      the lifespan in mice bearing sarcoma-180 tumors. Taken together, this is the
      first study indicating the anti-tumor effect of F. pinicola in vivo and in vitro.
      F. pinicola ethanol extract induces cell apoptosis to exert a significant anti
      tumor activity, with potential to be a new alternative anti-tumor medicine. 

PMID- 24566321
TI  - Synthesis, spectroscopic and theoretical studies of new quasi-podands from bile
      acid derivatives linked by 1,2,3-triazole rings.
AB  - A novel method for the synthesis of bile acid derivatives has been developed
      using "click chemistry". Intermolecular 1,3-dipolar cycloaddition of the
      propargyl ester of bile acids and azide groups of 1,3,5-tris(azidomethyl)benzene
      gave a new quasi-podands with 1,2,3-triazole rings. The structures of the
      products were confirmed by spectral (1H-NMR, 13C-NMR, and FT-IR) analysis, mass
      spectrometry and PM5 semiempirical methods. Estimation of the pharmacotherapeutic
      potential has been accomplished for synthesized compounds on the basis of
      Prediction of Activity Spectra for Substances (PASS). 

PMID- 24566323
TI  - Inhibition of human cytochrome P450 enzymes by Bacopa monnieri standardized
      extract and constituents.
AB  - Bacopa monnieri and the constituents of this plant, especially bacosides, possess
      various neuropharmacological properties. Like drugs, some herbal extracts and the
      constituents of their extracts alter cytochrome P450 (CYP) enzymes, causing
      potential herb-drug interactions. The effects of Bacopa monnieri standardized
      extract and the bacosides from the extract on five major CYP isoforms in vitro
      were analyzed using a luminescent CYP recombinant human enzyme assay. B. monnieri
      extract exhibited non-competitive inhibition of CYP2C19 (IC50/Ki = 23.67/9.5
      ug/mL), CYP2C9 (36.49/12.5 ug/mL), CYP1A2 (52.20/25.1 ug/mL); competitive
      inhibition of CYP3A4 (83.95/14.5 ug/mL) and weak inhibition of CYP2D6 (IC50 =
      2061.50 ug/mL). However, the bacosides showed negligible inhibition of the same
      isoforms. B. monnieri, which is orally administered, has a higher concentration
      in the gut than the liver; therefore, this herb could exhibit stronger inhibition
      of intestinal CYPs than hepatic CYPs. At an estimated gut concentration of 600
      ug/mL (based on a daily dosage of 300 mg/day), B. monnieri reduced the catalytic
      activities of CYP3A4, CYP2C9 and CYP2C19 to less than 10% compared to the total
      activity (without inhibitor = 100%). These findings suggest that B. monnieri
      extract could contribute to herb-drug interactions when orally co-administered
      with drugs metabolized by CYP1A2, CYP3A4, CYP2C9 and CYP2C19. 

PMID- 24566322
TI  - Synthetic Fosmidomycin analogues with altered chelating moieties do not inhibit 1
      deoxy-d-xylulose 5-phosphate Reductoisomerase or Plasmodium falciparum growth in
      vitro.
AB  - Fourteen new fosmidomycin analogues with altered metal chelating groups were
      prepared and evaluated for inhibition of E. coli Dxr, M. tuberculosis Dxr and the
      growth of P. falciparum K1 in human erythrocytes. None of the synthesized
      compounds showed activity against either enzyme or the Plasmodia. This study
      further underlines the importance of the hydroxamate functionality and
      illustrates that identifying effective alternative bidentate ligands for this
      target enzyme is challenging. 

PMID- 24566324
TI  - Glycosylation of a newly functionalized orthoester derivative.
AB  - Tandem glycosylation of the 6-O-Fmoc-substituted benzyl orthoester derivative 2a
      was carried out in moderate yields by electrogenerated acid (EGA). The Fmoc group
      was effectively removed under mild basic conditions, and the product was
      submitted to the subsequent glycosylation. 

PMID- 24566325
TI  - Triptolide induces s phase arrest and apoptosis in gallbladder cancer cells.
AB  - Gallbladder carcinoma is the most common malignancy of the biliary tract, with a
      very low 5-year survival rate and extremely poor prognosis. Thus, new effective
      treatments and drugs are urgently needed for the treatment of this malignancy. In
      this study, for the first time we investigated the effects of triptolide on
      gallbladder cancer cells and identified the mechanisms underlying its potential
      anticancer effects. The MTT assay showed that triptolide decreased cell viability
      in a dose- and time-dependent manner. The results of the colony formation assay
      indicated that triptolide strongly suppressed colony formation ability in GBC-SD
      and SGC-996 cells. Flow cytometric analysis revealed that triptolide induced S
      phase arrest in gallbladder cancer cells. In addition, triptolide induced
      apoptosis, as shown by the results of annexin V/propidium iodide double-staining
      and Hoechst 33342 staining. Furthermore, triptolide decreased mitochondrial
      membrane potential (DeltaPsim) in a dose-dependent manner. Finally, western blot
      analysis of triptolide-treated cells revealed the activation of caspase-3,
      caspase-9, PARP, and Bcl-2; this result demonstrated that triptolide induced
      apoptosis in gallbladder cancer cells by regulating apoptosis-related protein
      expression, and suggests that triptolide may be a promising drug to treat
      gallbladder carcinoma. 

PMID- 24566326
TI  - Three new tetranorditerpenes from aerial parts of acerola cherry (Malpighia
      emarginata).
AB  - Acerola cherry is a world famous fruit which contains abundant antioxidants such
      as vitamin C, anthocyanins, flavonoids, and phenolics. However, studies
      concerning bioactivity components from aerial parts of acerola (Malpighia
      emarginata) are scarce. In view of this, we have examined the constituents of
      aerial parts of acerola, and three new tetranorditerpenes acerolanins A-C (1-3)
      with a rare 2H-benz[e]inden-2-one substructure were isolated. Their structures
      were determined on the basis of spectral studies and acerolanin C was confirmed
      by X-ray crystallographic analysis. Furthermore, three new compounds have been
      studied for their cytotoxic activity. 

PMID- 24566327
TI  - Synthesis of a new class of Pyridazin-3-one and 2-amino-5-arylazopyridine
      derivatives and their utility in the synthesis of fused azines.
AB  - A general route for the synthesis of a novel class of pyridazin-3-one derivatives
      3 by the reaction in acetic anhydride between 3-oxo-2-arylhydrazonopropanals 1
      and some active methylene compounds like p-nitrophenylacetic acid and cyanoacetic
      acid was established. Under these conditions the pyridazin-3-one derivatives 3
      were formed as the sole isolable products in excellent yield. The 6-acetyl-3
      oxopyridazine derivative 3l was reacted with DMF-DMA to afford the corresponding
      enaminone derivative 4, which reacts with a variety of aminoazoles to afford the
      corresponding azolo[1,5-a]pyrimidine derivatives 5-7. Also, in order to explore
      the viability and generality of a recently uncovered reaction between 3-oxo-2
      arylhydrazonopropanals and active methylene compounds, a variety of 2-amino-6
      aryl-5-arylazo-3-aroylpyridines 16-19 were prepared by reacting 3-oxo-2
      arylhydrazonopropanals with miscellaneous active methylene compounds like 3-oxo-3
      phenylpropionitrile, hetaroylacetonitriles and cyanoacetamides. These 2
      aminopyridine derivatives undergo smooth reactions with cyanoacetic acid that led
      to the formation in high yield of a new class of 1,8-naphthyridine derivatives
      24. The structures of all new substances prepared in this investigation were
      determined by the different analytical spectroscopic methods, in addition to the
      X-ray crystallographic analysis. 

PMID- 24566328
TI  - Discovery of novel c-Met inhibitors bearing a 3-carboxyl piperidin-2-one
      scaffold.
AB  - A series of compounds containing a novel 3-carboxypiperidin-2-one scaffold based
      on the lead structure BMS-777607 were designed, synthesized and evaluated for
      their c-Met kinase inhibition and cytotoxicity against MKN45 cancer cell lines.
      The results indicated that five compounds exhibited significant inhibitory effect
      on c-Met with IC50 values of 8.6-81 nM and four compounds showed potent
      inhibitory activity against MKN45 cell proliferation, with IC50s ranging from
      0.57-16 MUM. 

PMID- 24566329
TI  - Comparative diagnostic techniques for cryptosporidium infection.
AB  - Diarrhoea caused by Cryptosporidium is usually mild in immune competent
      individuals but severe in the young and those with underlying disease leading to
      compromised immunity. The conventional diagnosis of Cryptosporidium requires
      observation of the infective oocysts however, their tiny size yields indistinct
      results, thus limiting the effectiveness of the conventional diagnostic
      technique, modified Ziehl-Neelsen (ZN) differential staining. Consequent to the
      abovementioned limitation, ZN staining, sandwich antigen detection enzyme linked
      immunosorbent assay (sad-ELISA) and a direct polymerase chain reaction (PCR)
      assay techniques were evaluated for diagnostic efficacy. Stool samples were
      collected from 180 consenting adult patients attending outpatient and inpatient
      clinics at Victoria Hospital, Alice, Eastern Cape Province of South Africa.
      Subjects were stratified as; 35 HIV-positive and diarrhoeagenic, 125 HIV-negative
      diarrhoeagenic and 20 apparently healthy controls. Cryptosporidium incidence
      following diagnostic techniques were 13 (37.1%; ZN staining), 26 (74.3%; sad
      ELISA) and 23 (65.7%; PCR), respectively, among HIV-positive diarrhoeagenic
      patients and 34 (27.2%; ZN staining), 96 (76.8%; sad-ELISA) and 89 (71.2%; PCR)
      among HIV-negative diarrhoeagenic patients. Sensitivity, specificity and
      predictive values of the diagnostic techniques' efficiency were: sensitivity:
      46.2% (HIV-positive) and 32.3% (HIV-negative) against the ZN technique and 96.9%
      against sad-ELISA and PCR, respectively, for both HIV-positive and -negative
      patients; specificity was 88.9% (HIV-positive) and 96.6% (HIV-negative) against
      the ZN technique. Lastly, the predictive values were 92.3% (HIV-positive) and
      96.9% (HIV-negative), respectively, following ZN staining. The sad-ELISA
      technique proved more suitable for the determination of the presence of
      Cryptosporidium oocysts. The high incidence of Cryptosporidium in HIV-positive
      subjects as compared to the HIV-negative population accentuates the significance
      of cryptosporidiosis diagnosis in the treatment and management of HIV cases. 

PMID- 24566330
TI  - Characteristics, composition and oxidative stability of Lannea microcarpa seed
      and seed oil.
AB  - The proximate composition of seeds and main physicochemical properties and
      thermal stability of oil extracted from Lannea microcarpa seeds were evaluated.
      The percentage composition of the seeds was: ash (3.11%), crude oil (64.90%),
      protein (21.14%), total carbohydrate (10.85%) and moisture (3.24%).
      Physicochemical properties of the oil were: refractive index, 1.473; melting
      point, 22.60 degrees C; saponification value, 194.23 mg of KOH/g of oil; iodine
      value, 61.33 g of I2/100 g of oil; acid value, 1.21 mg of KOH/g of oil; peroxide
      value, 1.48 meq of O2/kg of oil and oxidative stability index, 43.20 h. Oleic
      (43.45%), palmitic (34.45%), linoleic (11.20%) and stearic (8.35%) acids were the
      most dominant fatty acids. Triacylglycerols with equivalent carbon number (ECN)
      48 and ECN 46 were dominant (46.96% and 37.31%, respectively). The major
      triacylglycerol constituents were palmitoyl diolein (POO) (21.23%), followed by
      dipalmitoyl olein (POP) (16.47%), palmitoyl linoleyl olein (PLO) (12.03%),
      dipalmitoyl linolein (PLP) (10.85%) and dioleoyl linolein (LOO) (9.30%). The
      total polyphenol and tocopherol contents were 1.39 mg GAE g-1 DW and 578.56 ppm,
      respectively. gamma-Tocopherol was the major tocopherol (437.23 ppm). These
      analytical results indicated that the L. microcarpa seed oil could be used as a
      frying oil and in the cosmetic industry. 

PMID- 24566331
TI  - Synthesis and biological evaluation of substituted desloratadines as potent
      arginine vasopressin V2 receptor antagonists.
AB  - Twenty-one non-peptide substituted desloratadine class compounds were synthesized
      as novel arginine vasopressin receptor antagonists from desloratadine via
      successive acylation, reduction and acylation reactions. Their structures were
      characterized by 1H-NMR and HRMS, their biological activity was evaluated by in
      vitro and in vivo studies. The in vitro binding assay and cAMP accumulation assay
      indicated that these compounds are potent selective V2 receptor antagonists.
      Among them compounds 1n, 1t and 1v exhibited both high affinity and promising
      selectivity for V2 receptors. The in vivo diuretic assay demonstrated that 1t
      presented remarkable diuretic activity. In conclusion, 1t is a potent novel AVP
      V2 receptor antagonist candidate. 

PMID- 24566332
TI  - A systematic review of organ motion and image-guided strategies in external beam
      radiotherapy for cervical cancer.
AB  - Advanced radiotherapy techniques, such as intensity-modulated radiotherapy
      (IMRT), may significantly benefit cervical cancer patients, in terms of reducing
      late toxicity and potentiating dose escalation. Given the steep dose gradients
      around the planning target volume (PTV) with IMRT planning, internal movement of
      organs during treatment may cause geographical miss of the target and unnecessary
      organs at risk (OAR) inclusion into high dose regions. It is therefore important
      to consider the extent and patterns of organ motion and to investigate potential
      image-guided radiotherapy (IGRT) solutions before implementing IMRT for cervical
      cancer. A systematic literature search was carried out using Medline, Embase,
      Cochrane Library, Web of Science, Cinahl and Pubmed. Database-appropriate search
      strategies were developed based upon terms for uterine neoplasms, IGRT, organ
      motion and target volume. In total, 448 studies were identified and screened to
      find 39 relevant studies, 12 of which were abstracts. These studies show that
      within the target volume for cervical cancer radiotherapy, uterine motion is
      greater than cervical. Uterine motion is predominantly influenced by bladder
      filling, cervical motion by rectal filling. Organ motion patterns are patient
      specific, with some having very little (5 mm) and others having much larger
      shifts (40 mm) of the target volume. Population-based clinical target volume
      (CTV)-PTV margins would be large (up to 4 cm around the uterus), resulting in
      unnecessary OAR inclusion within the PTV, reducing the benefits of IMRT.
      Potential solutions include anisotropic margins with increased margins in the
      anteroposterior and superoinferior directions, or greater PTV margins around the
      uterine fundus than the cervix. As pelvic organ motion seems to be patient
      specific, individualised PTV margins and adaptive IGRT strategies have also been
      recommended to ensure target volume coverage while increasing OAR sparing.
      Although these strategies are promising, they need significant validation before
      they can be adopted into clinical practice. 

PMID- 24566333
TI  - Simultaneous determination of five free and total flavonoids in rat plasma by
      ultra HPLC-MS/MS and its application to a comparative pharmacokinetic study in
      normal and hyperlipidemic rats.
AB  - A simple and rapid ultra-high performance liquid chromatography-tandem mass
      spectrometry (uHPLC-MS/MS) method has been developed for the simultaneous
      determination of five free flavonoids (amentoflavone, isorhamnetin, naringenin,
      kaempferol and quercetin) and their total (free and conjugated) forms, and to
      compare the pharmacokinetics of these active ingredients in normal and
      hyperlipidemic rats. The free and total forms of these flavonoids were extracted
      by liquid-liquid extraction with ethyl acetate. The conjugated flavonoids were
      deconjugated by the enzyme beta-Glucuronidase and Sulfatase. Chromatographic
      separation was accomplished on a ZORBAX Eclipse XDB-C8 USP L7 column using
      gradient elution. Detection was performed on a 4000Q uHPLC-MS/MS system from AB
      Sciex using negative ion mode in the multiple reaction monitoring (MRM) mode. The
      lower limits of quantification were 2.0-5.0ng/mL for all the analytes. Intra-day
      and inter-day precision were less than 15% and accuracy ranged from -9.3% to
      11.0%, and the mean extraction recoveries of analytes and internal standard (IS)
      from rat plasma were all more than 81.7%. The validated method was successfully
      applied to a comparative pharmacokinetic study of five free and total analytes in
      rat plasma. The results indicated that the absorption of five total flavonoids in
      hyperlipidemia group were significantly higher than those in normal group with
      similar concentration-time curves. 

PMID- 24566335
TI  - Prevalence of undiagnosed chronic thromboembolic pulmonary hypertension after
      pulmonary embolism.
AB  - Chronic thromboembolic pulmonary hypertension is associated with adverse
      prognosis. Early diagnosis is important to better identify patients who would
      benefit from a well established therapeutic strategy. The purpose of our study
      was to evaluate long-term incidence of undiagnosed chronic thromboembolic
      pulmonary hypertension after acute pulmonary embolism and the utility of a long
      term follow-up including an echocardiographic-based screening programme to early
      detect this disease. We evaluated retrospectively 282 patients discharged from
      the 'Maggiore della Carita' Hospital, Universita del Piemonte Orientale, Novara,
      Italy, with diagnosis of acute pulmonary embolism between November 2006 and
      October 2009. One hundred and eleven patients underwent a clinical late
      echocardiographic screening programme after the acute event. Patients with
      suspected pulmonary hypertension based on echocardiographic evidence of systolic
      pulmonary artery pressure of at least 40  mmHg underwent complete work-up for
      chronic thromboembolic pulmonary hypertension assessment, including ventilation
      perfusion lung scintigraphy and right heart catheterization. One hundred and
      eleven patients were included in the study. Pulmonary hypertension was suspected
      in 15 patients; five patients had chronic thromboembolic pulmonary hypertension
      confirmed by ventilation-perfusion lung scintigraphy, right heart catheterization
      and pulmonary angiography. Two patients with clinical class functionally advanced
      underwent surgical pulmonary endarterectomy and two asymptomatic patients
      underwent medical treatment. The prevalence of undiagnosed chronic thromboembolic
      pulmonary hypertension was 4.5%. Chronic thromboembolic pulmonary hypertension is
      a serious disease with a poor prognosis if not treated early. Surgical treatment
      is decisive. After surgery, the majority of patients have a substantial
      improvement in their functional status and in haemodynamic variables. Many
      patients are asymptomatic. Implementation of screening programmes may be helpful
      for an early diagnosis and early proper therapy.

PMID- 24566334
TI  - Characterization of metabolic profile of honokiol in rat feces using liquid
      chromatography coupled with quadrupole time-of-flight tandem mass spectrometry
      and (13)C stable isotope labeling.
AB  - As fecal excretion is one of important routes of elimination of drugs and their
      metabolites, it is indispensable to investigate the metabolites in feces for more
      comprehensive information on biotransformation in vivo. In this study, a
      sensitive and reliable approach based on ultra-performance liquid
      chromatography/quadrupole-time-of-flight-mass spectrometry (UHPLC-Q-TOF-MS) was
      applied to characterize the metabolic profile of honokiol in rat feces after the
      administration of an equimolar mixture of honokiol and [(13)C6]-labeled honokiol.
      Totally 42 metabolites were discovered and tentatively identified in rat feces
      samples, 26 metabolites were first reported, including two novel classes of
      metabolites, methylated and dimeric metabolites of honokiol. Moreover, this study
      provided basic comparative data on the metabolites in rat plasma, feces and
      urine, which gave better understanding of the metabolic fate of honokiol in vivo.

PMID- 24566337
TI  - A case of persistent dizziness after travel.
AB  - Although vertigo is a common complaint with patients presenting to an ED, some
      uncommon causes also must be considered. This report focuses on a woman who
      developed sudden-onset vertigo with associated mental status changes after a long
      distance flight. Her symptoms were consistent with mal de debarquement syndrome,
      an uncommon cause of vestibular dysfunction. 

PMID- 24566336
TI  - The T-cell-dependent antibody response assay in nonclinical studies of
      pharmaceuticals and chemicals: study design, data analysis, interpretation.
AB  - The T-cell-dependent antibody response (TDAR) assay is a measure of immune
      function that is dependent upon the effectiveness of multiple immune processes,
      including antigen uptake and presentation, T cell help, B cell activation, and
      antibody production. It is used for risk and safety assessments, in conjunction
      with other toxicologic assessments, by the chemical and pharmaceutical
      industries, and research and regulatory agencies. It is also employed to evaluate
      investigational drug efficacy in animal pharmacology studies, provide evidence of
      biological impact in clinical trials, and evaluate immune function in patients
      with primary or secondary immunodeficiency diseases. Various immunization
      schemes, analytical methods, approaches to data analysis, and data
      interpretations are in use. This manuscript summarizes some recommended practices
      for the conduct and interpretation of the assay in animal studies. 

PMID- 24566339
TI  - What are extended-spectrum beta-lactamases?
AB  - The emergence and spread of extended-spectrum beta-lactamases (ESBLs) in Gram
      negative bacteria pose important challenges for clinicians, as management options
      for these organisms are limited. The emergence of ESBL-producing Gram-negative
      bacteria is one of the most significant epidemiologic changes in infectious
      diseases during recent years. Failure to treat with an antibiotic active against
      ESBL-producing organisms is associated with increased patient morbidity and
      mortality. Carbapenems are considered the primary antibacterials for infections
      caused by ESBL-producing organisms but their overuse poses significant cause for
      concern. 

PMID- 24566340
TI  - What is this streaky rash?

PMID- 24566342
TI  - A woman with sensory deficits, paresthesias, and ataxia.
AB  - Multiple sclerosis (MS) is a demyelinating and inflammatory disease that is
      thought to be autoimmune in nature. MS typically affects young women ages 20 to
      40 years, but late-onset MS (after age 50 years) is more prevalent than
      previously thought. Between 4% and 9% of patients with MS have symptoms onset
      after age 50 years. 

PMID- 24566343
TI  - Supply of physician assistants: 2013-2026.
AB  - As part of healthcare reform, physician assistants (PAs) are needed to help
      mitigate the physician shortage in the United States. This requires understanding
      the population of clinically active PAs for accurate prediction purposes. An
      inventory projection model of PAs drew on historical trends, the PA stock,
      graduation estimates, retirement trends, and PA intent to retire data. A new
      source of licensed health professionals, Provider 360 Database, was obtained to
      augment association information. Program growth and graduate projections
      indicated an annual 4.7% trend in new entrants to the workforce, offset by annual
      attrition estimates of 2.9%. As of 2013, there were 84,064 licensed PAs in the
      United States. The stock and flow equation conservatively predicts the supply of
      PAs to be 125,847 by 2026. Although the number of clinically active PAs is
      projected to increase at least by half by 2026, substantial gaps remain in
      understanding career trends and early attrition influences. Furthermore,
      education production could be constrained by inadequate clinical training sites
      and scarcity of faculty. 

PMID- 24566344
TI  - Persistent hip pain despite normal radiographs.
AB  - Acetabular fractures are frequently missed on plain view radiographs of the hip
      and pelvis. A high degree of clinical suspicion for an acetabular fracture should
      be maintained in any patient with persistent traumatic hip, pelvic, or buttock
      pain, and inability to ambulate. 

PMID- 24566345
TI  - Acute pericarditis.

PMID- 24566346
TI  - The role of primary care physician assistants in managing chronic hepatitis B.
AB  - This article informs physician assistants of an algorithm designed for primary
      care practice to guide the screening of patients for hepatitis B virus infection.
      The algorithm also provides guidance on evaluation, follow-up, and referral of
      patients who screen positive. The algorithm is a synthesis of several published,
      evidence-based practice guidelines and reports. 

PMID- 24566347
TI  - An unusual case of female abdominal pain.

PMID- 24566348
TI  - Splints.

PMID- 24566349
TI  - Generalised electrographic seizures presenting as perioral myoclonia.
AB  - A 41-year-old man, during a neurological consultation, reported "chin twitching"
      over a period of a week, which was diagnosed as intermittent perioral myoclonia.
      With only one tonic-clonic seizure seven years before, he had mentioned several
      episodes of chin twitching over the years. In the clinic, there were intermittent
      chin movements without apparent confusion, as he was able to provide a complete
      history and was fully oriented with intact memory. His video-EEG showed paroxysms
      of polyspike and slow-wave activity, with the longest burst-free interval being
      20 seconds. Discharges were maximal over the fronto-central regions, correlating
      with the chin myoclonus. He was able to tap his hand continuously, and remained
      alert. The case represents an atypical presentation of idiopathic generalised
      epilepsy without manifestation of absence or limb myoclonus. Although juvenile
      myoclonic epilepsy and other idiopathic epilepsies are rarely associated with
      perioral myoclonia, this sign was the principal clinical feature for this
      patient. Oral treatment with levetiracetam resolved his seizures.

PMID- 24566350
TI  - Clean water and sanitation in developing areas lacking conventional power.
AB  - Progress in providing clean water and sanitation throughout the developing world
      has been steady and encouraging, even though UN Millennium Development Goals will
      not be completely met. A number of important lessons have been learned along the
      way with respect to point-of-use water treatment and sanitation devices that are
      appropriate for deployment in remote areas where power and clean water are not
      available. Here, prominent point-of-use treatment systems are compared in terms
      of disinfection capability, durability and cost, and lessons learned regarding
      the provision of improved sanitation are reviewed.

PMID- 24566351
TI  - Striving for success in sanitation, hygiene, and water supply.
AB  - An estimated 800,000 people do not have access to improved water sources, and 2.5
      billion are without access to improved sanitation. As a result, an estimated 1800
      children under 5 years of age die every day from preventable diseases related to
      water, sanitation & hygiene; more are ill or stunted. To sustainably improve
      people's health, actors in the water sector at all levels should use flexible,
      integrated approaches focused on behavior change and service delivery. Approaches
      and technologies should be as simple as possible while still protecting human
      health and the environment. Remember, it's not just about the toilet.

PMID- 24566352
TI  - Nanotechnology in environmental remediation: degradation of volatile organic
      compounds (VOCs) over visible-light-active nanostructured materials.
AB  - Volatile organic compounds (VOCs) are major pollutants and are considered to be
      one of the most important contaminants generated by human beings living in urban
      and industrial areas. Methyl tert-butyl ether (MTBE) is a VOC that has been
      widely used as a gasoline additive to reduce VOC emissions from motor vehicles.
      However, new gasoline additives like MTBE are having negative environmental
      impacts. Recent survey reports clearly show that groundwater is often polluted
      owing to leakage of petroleum products from underground storage tanks. MTBE is
      highly soluble in water (e.g., 0.35-0.71 M) and has been detected at high
      concentrations in groundwater. The presence of MTBE in groundwater poses a
      potential health problem. The documented effects of MTBE exposure are headaches,
      vomiting, diarrhea, fever, cough, muscle aches, sleepiness, disorientation,
      dizziness, and skin and eye irritation. To address these problems, photocatalytic
      treatment is the preferred treatment for polluted water. In the present work, a
      simple and template-free solution phase synthesis method has been developed for
      the preparation of novel cadmium sulfide (CdS) hollow microspheres using cadmium
      nitrate and thioacetamide precursors. The synthesized products have been
      characterized by a variety of methods, including X-ray powder diffraction, high
      resolution scanning electron microscopy (HR-SEM), X-ray photoelectron
      spectroscopy, and UV-visible diffused reflectance spectroscopy. The HR-SEM
      measurements revealed the spherical morphology of the CdS microspheres, which
      evolved by the oriented aggregation of the primary CdS nanocrystals. Furthermore,
      studies of photocatalytic activity revealed that the synthesized CdS hollow
      microspheres exhibit an excellent photocatalytic performance in rapidly degrading
      MTBE in aqueous solution under visible light illumination. These results suggest
      that CdS microspheres will be an interesting candidate for photocatalytic
      detoxification studies under visible light radiation.

PMID- 24566353
TI  - Combating infectious diseases in the Pacific Islands: sentinel surveillance,
      environmental health, and geospatial tools.
AB  - Infectious diseases are responsible for significant disease burden in the Pacific
      Islands. Environmental drivers of disease transmission and public health
      challenges vary between diseases, at times of emergence versus outbreaks, and
      also during the last stages of elimination where prevalence is low. In order to
      more effectively combat infectious diseases in the region, innovative approaches
      such as sentinel surveillance, environmental monitoring, the use of geospatial
      tools should be explored.

PMID- 24566354
TI  - Fine particles characterization in residential homes located in different
      microenvironment of India.
AB  - Aerosol Spectrometer was used for monitoring the indoor and outdoor mass
      concentration of fine PM2.5, PM1.0, PM0.5 and PM0.25 in homes, located in urban,
      roadside and rural area of Agra city located in the north central part of India.
      For chemical characterization samples are collected with medium volume sampler on
      PTFE filters. The collected filters were extracted in an ultrasonic extractor for
      the determination of water soluble ions. Concentrations for F-, Cl-, NO3-, and
      SO42- were determined by ion chromatography. Na+, K+, Ca2+, Ba+, and Mg2+
      determined by Atomic Absorption Spectrometer. The trends of particulate mass
      concentration indoors were rural>roadside>urban and for outdoors were
      roadside>rural>urban. PM2.5 concentration in our results exceeded WHO guidelines
      by 8-10 times for outdoor and by 7-9 times for the indoor environment during the
      collection period. Water soluble species ranged from 60% to 92% (Avg 72%, SD 13%)
      for PM2.5 total mass. The total sum of ionic concentrations in PM2.5 follow the
      same trend as that by mass concentration. The average I/O ratios are found to be
      higher in PM2.5 particles at rural and roadside sites indicating additional
      sources indoors at these sites.

PMID- 24566355
TI  - Respiratory health risk assessment of children living close to industrial areas
      in Indonesia.
AB  - Industrial areas are considered to have higher risk of air pollution impact
      especially to children living close to the industry. Two separate industrial
      areas in Indonesia were compared. The first location was in the area of coal
      transportation activity in South Kalimantan, and the second location was in the
      area of Bogor, West Java where used battery processing industry was often found.
      Fifty children (boys and girls, aged 6-15 years) were involved in South
      Kalimantan whereas in West Java there were 48 children (boys and girls, aged 10
      12 years) involved. The control groups were also studied in both areas. Predicted
      average daily intake (ADD) of respirable particulate was estimated and
      respiratory function was measured using spirometer. The study showed that the
      PM2.5 concentration in industrial area was 3 times higher than those found in the
      control location. As a result, the predicted ADD of particulate of children
      living close to industry in South Kalimantan was 25.45+/-10.55 ug/kg.day whereas
      in West Java, the ADD was 1.5 times higher. For both studied area, boys'
      respirable particulate intake was shown to have higher intake than those in
      girls. Lung function of children revealed that more than 68% of children in the
      coal transportation area had decreased pulmonary function. The study also noted
      that some children in West Java had indicated an obstructive and restrictive
      respiratory condition. The risk of girls having mild lung disease was found to be
      1.3 times greater than those in the control group whereas in boys, the risk was
      1.9 times than those in control area. Respiratory function of children in West
      Java study area was considered to worsen by the higher Pb emission from used
      battery processing activity.

PMID- 24566356
TI  - Chemical exposure and respiratory health of children in an industrial setting.
AB  - BACKGROUND: Parental exposures to chemicals, and the interplay between chemical
      exposures in utero and in infancy leading to respiratory disease in childhood,
      are not yet fully understood. In this study we investigated the impact of
      chemical exposures to the parent in occupational settings and to the child in the
      home and children's respiratory health. METHODS: A cross-sectional study of lung
      function and respiratory health was conducted in primary school children in the
      Kwinana industrial area, south of Perth, Western Australia. Respiratory health
      was assessed using a standardized questionnaire and lung function was measured
      using the forced oscillation technique before and after inhaling 200 MUg of
      salbutamol. Univariate logistic regression models were used to explore the
      relationship between the child's respiratory health (asthma, lung function,
      bronchodilator response) and exposures to ceramics, dry cleaning fluid,
      electroplating fluid, glues, leather, fabrics, dyes, insecticides, plastics,
      metal cleaning fluid, petrol, paint, photochemicals, electric wiring, machining,
      welding, X-rays, cleaning products, nail products, and "other exposures". The
      impact of cigarette smoking in the home and family history on respiratory health
      were also investigated. RESULTS: No associations were found between parental
      occupational exposures or child's exposures in the home and respiratory health.
      Significant associations were observed between current smoking in the home and
      cigarette exposure in the first year of life and poor respiratory health in the
      children. CONCLUSION: We found no strong evidence of main effects of occupational
      exposures in impairing the respiratory health of primary school-aged children.

PMID- 24566357
TI  - Cesarean section and placental disorders in subsequent pregnancies--a meta
      analysis.
AB  - BACKGROUND: Despite an increase in the number of cesarean deliveries conducted
      worldwide, meta-analyses on the long-term effect of cesarean section (CS) on
      subsequent placental disorders are sparse. OBJECTIVE: To examine the association
      between CS and three major types of placental disorders (placental abruption,
      placenta previa, and placenta accreta with its variants increta/percreta) in
      subsequent pregnancies. SEARCH STRATEGY: We followed the MOOSE consensus
      statement for meta-analyses of observational studies and searched the PubMed
      database for observational studies published between January 1990 and July 2011
      for examining the association between CS and placental disorders in subsequent
      pregnancies, without focusing on the effect of increasing number of CSs.
      SELECTION CRITERIA: We included studies which provided adjusted measures of
      association for multiparous singleton-pregnant women with one of the three
      outcomes and information about prior mode of delivery. DATA COLLECTION AND
      ANALYSIS: Five cohort and 11 case-control studies met the inclusion criteria for
      this meta-analysis. We combined the results of the included cohort and case
      control studies as no significant heterogeneity was found across the studies.
      MAIN RESULTS: The calculated summary odds ratio was 1.47 (95% confidence
      interval, CI: 1.44-1.51) for placenta previa, 1.96 (95% CI: 1.41-2.74) for
      placenta accreta, and 1.38 (95% CI: 1.35-1.41) for placental abruption.
      CONCLUSION: In this meta-analysis, cesarean delivery appeared as a consistently
      reported risk factor for all three major forms of placental disorders in
      subsequent pregnancies.

PMID- 24566359
TI  - Neonatal diabetes in an infant of diabetic mother: same novel INS missense
      mutation in the mother and her offspring.
AB  - Neonatal diabetes is defined as an uncontrolled hyperglycemic state occurring
      within the first 6 months of life. It is a rare disease with an incidence of 1 to
      90,000-250,000. It is usually a disease of genetic origin in which insulin gene
      mutations play the main role in the disease process. A baby, born to a mother who
      had previously been diagnosed with type 1 diabetes mellitus at 14 months of age,
      had a high blood sugar level within the first few hours after birth and was
      subsequently diagnosed as having neonatal diabetes mellitus. Baby and mother were
      identified as having a novel heterozygous insulin missense mutation, p.C109R.
      Difficulties occurred in both follow-up and feeding of the baby. Without the
      addition of the mother's milk, an appropriate calorie milk formula and isophane
      insulin were used for the baby during follow-up. Multiple mechanisms are
      responsible in the pathogenesis of neonatal diabetes mellitus. Insulin gene
      mutations are one of the factors in the development of neonatal diabetes
      mellitus. If a resistant hyperglycemic state persists for a long time among
      babies, especially in those with intrauterine growth retardation whose mothers
      are diabetic, the baby concerned should be followed-up carefully for the
      development of neonatal diabetes mellitus.

PMID- 24566358
TI  - Effect of magnesium sulfate and nifedipine on the risk of developing pulmonary
      edema in preterm births.
AB  - OBJECTIVE: To evaluate the risk of developing pulmonary edema in women exposed to
      nifedipine, magnesium sulfate (MgSO4), or both in a preterm setting. STUDY
      DESIGN: We carried out a retrospective case-control study at a large tertiary
      care center from 2007 to 2012. Cases of pulmonary edema were age, and gestational
      age matched to controls at a ratio of 1 case to 4 controls. Logistic regression
      analysis was used to estimate the effect of nifedipine and/or MgSO4 on the
      development of pulmonary edema while controlling for predetermined confounding
      variables. Stepwise logistic regression analysis was used to evaluate additional
      risk factors of pulmonary edema. RESULTS: A total of 150 charts were reviewed (28
      cases and 122 controls). Nifedipine did not increase the odds of developing
      pulmonary edema [adjusted odds ratio (OR)=1.22 (confidence interval (CI) 0.50,
      3.01), P=0.67], whereas exposure to MgSO4, or both MgSO4 and nifedipine,
      significantly increased the risk of developing pulmonary edema [adjusted OR=3.91
      (CI 1.44, 10.65), P=0.008 and adjusted OR=4.75 (CI 1.15, 19.71), P=0.032,
      respectively]. In the stratified analysis, this association persisted even in
      nonpreeclamptic women [nifedipine: adjusted OR=0.91 (CI 0.33, 2.52), P=0.852;
      MgSO4: adjusted OR=3.51 (CI 1.26, 9.76), P=0.016; both: adjusted OR=3.39 (0.76,
      15.07), P=0.108]. Other independent risk factors for pulmonary edema were multi
      fetal pregnancy, azithromycin, and erythromycin administration. CONCLUSION: MgSO4
      treatment is strongly associated with the development of pulmonary edema when
      used either as a tocolytic agent or for seizure prophylaxis. In light of the
      availability of safer alternatives, MgSO4 should be used for tocolysis only in
      cases whereby the benefits clearly outweigh the risks.

PMID- 24566360
TI  - Evaluation of insulin resistance and metabolic syndrome in a group of obese Czech
      children.
AB  - OBJECTIVE: The study aimed to determine the incidence of metabolic syndrome (MS)
      in a group of Czech obese children, to evaluate the incidence of insulin
      resistance according to HOMA-IR in this group, and to consider the diagnostic
      value of HOMA-IR in early MS detection in obese children using the logistic
      regression models for analyzing the relations between HOMA IR and MS. SUBJECTS
      AND METHODS: Anthropometric and laboratory examinations were performed in a group
      of 274 obese children aged 10-17 years. RESULTS: MS was established in 102
      subjects (37%). The presence of insulin resistance according to HOMA-IR >3.16 was
      ascertained in 53% of the subjects. HOMA-IR limit was exceeded by 70% in the MS
      (+) group and by 43% in children in the MS (-) (p<0.0001) category. CONCLUSION:
      The relatively high incidence of insulin resistance in obese children without MS
      questions the prevailing diagnostic criteria of, perhaps, falsely excluding some
      cases of, MS.

PMID- 24566361
TI  - Possible roles of astrocytes in estrogen neuroprotection during cerebral
      ischemia.
AB  - 17beta-Estradiol (E2), one of female sex hormones, has well-documented
      neuroprotective effects in a variety of clinical and experimental disorders of
      the central cerebral ischemia, including stroke and neurodegenerative diseases.
      The cellular mechanisms that underlie these protective effects of E2 are
      uncertain because a number of different cell types express estrogen receptors in
      the central nervous system. Astrocytes are the most abundant cells in the central
      nervous system and provide structural and nutritive support of neurons. They
      interact with neurons by cross-talk, both physiologically and pathologically.
      Proper astrocyte function is particularly important for neuronal survival under
      ischemic conditions. Dysfunction of astrocytes resulting from ischemia
      significantly influences the responses of other brain cells to injury. Recent
      studies demonstrate that estrogen receptors are expressed in astrocytes,
      indicating that E2 may exert multiple regulatory actions on astrocytes. Cerebral
      ischemia induced changes in the expression of estrogen receptors in astrocytes.
      In the present review, we summarize the data in support of possible roles for
      astrocytes in the mediation of neuroprotection by E2 against cerebral ischemia.

PMID- 24566362
TI  - Synapses need coordination to learn motor skills.
AB  - Experience-dependent remodeling of synaptic structure and function underlies
      information storage in the mammalian central nervous system. Although
      accumulating evidence suggests synergistic roles of long-term depression (LTD)
      and long-term potentiation (LTP) in cerebellar motor learning, their structural
      correlates and operational mechanisms have not been clearly addressed. A recent
      three-dimensional electron microscopic study provides insight for a potential
      complementary interplay between LTP and LTD in local dendritic segments of
      Purkinje cells of motor skill-trained animals. Complex motor skill training
      induced strengthening of a subset of parallel fiber synapses onto Purkinje cells
      by forming multiple-synapse boutons (MSBs) contacting spine pairs arising from
      the same dendrite, whereas MSB-neighboring synapses were weakened by reducing the
      size of the postsynaptic density. Here, we discuss these orchestrated structural
      modifications of neighboring synapses that may sharpen synaptic weight contrast
      in local dendritic segments, leading to enhanced signal-to-noise ratio for
      optimal motor skill retention.

PMID- 24566363
TI  - Why calcium channel blockers could be an elite choice in the treatment of
      Alzheimer's disease: a comprehensive review of evidences.
AB  - The universality and vitality of calcium ions are implicit from its diverse
      physiological functions, from regulation of enzymes to synaptic plasticity and
      memory. However, overloading of these ions could result in life-threatening
      degenerative disorders. Calcium channels, which are involved in the transport of
      calcium ions, are targeted and blocked to prevent its overload, favoring vascular
      relaxation. Besides this primary action, calcium channel blockers (CCBs) also
      genuinely exhibit cognitive-enhancing abilities and reduce the risk of dementia,
      especially of Alzheimer's type. Alzheimer's disease (AD) is triggered by the
      disruption of calcium homeostasis, which underlies the observed progressive
      cognitive decline that occurs in this neurodegenerative disorder. Fortunately,
      CCB is expected to offer neuroprotection and additionally demonstrate
      antiamyloid, antitau, antiphospholipase, antiplatelet, antioxidant, and anti
      inflammatory activity, a solitary solution to all the subcellular physiological
      complications that are observed in AD. Therefore, the aim of this review was to
      unearth the prospective of CCB against cognitive frailty with a sole purpose of
      elucidating CCB as cognitive enhancers, which could find its use as a drug in
      prevention or treatment of AD.

PMID- 24566364
TI  - Method-specific differences in beta-isomerised carboxy-terminal cross-linking
      telopeptide of type I collagen and procollagen type I amino-terminal propeptide
      using two fully automated immunoassays.

PMID- 24566365
TI  - A statistical basis for harmonization of thyroid stimulating hormone immunoassays
      using a robust factor analysis model.
AB  - BACKGROUND: Between-method equivalence ideally is achieved by calibration against
      an SI-traceable reference measurement procedure. For measurement of thyroid
      stimulating hormone (TSH), it is unlikely to accomplish this goal in mid-term.
      Therefore, we investigated a statistical alternative based on a factor analysis
      (FA) model. METHODS: The FA model was applied to TSH results for 94 samples
      generated by 14 immunoassays (concentration range: 0.0005-78 mIU/L). The dataset
      did not fulfill the assumption of a homogeneous sample from an elliptically
      symmetric distribution, and, therefore, required standardization prior to
      application of the FA model. As outliers and missing values also occurred, the
      key quantities of the FA model had to be estimated with a method that can handle
      these complications. We selected a robust alternating regressions (RAR) method,
      which replaces in the minimization criterion of the fitting process the squared
      differences between results xij and model fit x^ij ${?hat x_{ij}}$ by a weighted
      absolute difference. The weights are adaptively determined in successive
      regressions, which down weighs the outliers. The weights for missing values are
      set to zero. RESULTS: The quality of the estimated targets was reflected by their
      central position in the distributions, and description of the relationship
      between results and targets by a simple two-parameter regression equation with
      high correlation coefficients and low SDs of the percentage-residuals.
      Mathematical recalibration eliminated the method differences and improved the
      between-method CV from 11% to 6%. CONCLUSIONS: RAR applied to a multimethod
      comparison dataset hampered by outliers and missing values, is fit to the purpose
      of harmonization.

PMID- 24566366
TI  - Digoxin overdose--an accurate method for determining free digoxin concentrations
      on general chemistry analysers post DigiFab treatment.

PMID- 24566367
TI  - Evaluation of Calfast(r) immunochromatographic quantitative assay for the
      measurement of calprotectin in faeces.

PMID- 24566368
TI  - Combined light chain immunofixation to detect monoclonal gammopathy: a comparison
      to standard electrophoresis in serum and urine.
AB  - BACKGROUND: The purpose of this study was to evaluate a combined kappa and lambda
      light chain immunofixation (CLIF) as a screening tool to detect monoclonal
      immunoglobulins in serum and urine. A secondary aim was to investigate the impact
      on workflow and reagent utilisation of a systematic implementation of CLIF in
      addition to routine protein electrophoresis (PE) on all samples. METHODS: Light
      chain antisera (kappa and lambda) were mixed in a 1:1 ratio and loaded in the
      same sequence as the PE to create a superimposable image. RESULTS: The CLIF
      procedure agreed significantly better with standard immunofixation procedures in
      the serum and urine. In 33 (22%) new patients and in 114 (15%) follow-up patients
      CLIF detected a band missed by PE in serum. In 34 (4.5%) of previously
      categorised cases the monoclonal band was below the detection limit of CLIF in
      serum, but still detectable by conventional immunofixation electrophoresis. In
      one case (0.7%) a band in a urine specimen was missed by CLIF compared to 70
      (49%) missed by PE. After the systematic introduction of CLIF turn-around-times
      (TATs) and utilisation of laboratory consumables decreased significantly
      (p<0.001). CONCLUSIONS: A systematic implementation of CLIF led to the detection
      of monoclonal bands missed by PE with an improvement in TATs and a decrease in
      cost.

PMID- 24566369
TI  - Locally efficient estimation of marginal treatment effects when outcomes are
      correlated: is the prize worth the chase?
AB  - Semiparametric methods have been developed to increase efficiency of inferences
      in randomized trials by incorporating baseline covariates. Locally efficient
      estimators of marginal treatment effects, which achieve minimum variance under an
      assumed model, are available for settings in which outcomes are independent. The
      value of the pursuit of locally efficient estimators in other settings, such as
      when outcomes are multivariate, is often debated. We derive and evaluate
      semiparametric locally efficient estimators of marginal mean treatment effects
      when outcomes are correlated; such outcomes occur in randomized studies with
      clustered or repeated-measures responses. The resulting estimating equations
      modify existing generalized estimating equations (GEE) by identifying the
      efficient score under a mean model for marginal effects when data contain
      baseline covariates. Locally efficient estimators are implemented for
      longitudinal data with continuous outcomes and clustered data with binary
      outcomes. Methods are illustrated through application to AIDS Clinical Trial
      Group Study 398, a longitudinal randomized clinical trial that compared the
      effects of various protease inhibitors in HIV-positive subjects who had
      experienced antiretroviral therapy failure. In addition, extensive simulation
      studies characterize settings in which locally efficient estimators result in
      efficiency gains over suboptimal estimators and assess their feasibility in
      practice.

PMID- 24566370
TI  - Variance and covariance heterogeneity analysis for detection of metabolites
      associated with cadmium exposure.
AB  - In this study, we propose a novel statistical framework for detecting progressive
      changes in molecular traits as response to a pathogenic stimulus. In particular,
      we propose to employ Bayesian hierarchical models to analyse changes in mean
      level, variance and correlation of metabolic traits in relation to covariates. To
      illustrate our approach we investigate changes in urinary metabolic traits in
      response to cadmium exposure, a toxic environmental pollutant. With the
      application of the proposed approach, previously unreported variations in the
      metabolism of urinary metabolites in relation to urinary cadmium were identified.
      Our analysis highlights the potential effect of urinary cadmium on the variance
      and correlation of a number of metabolites involved in the metabolism of choline
      as well as changes in urinary alanine. The results illustrate the potential of
      the proposed approach to investigate the gradual effect of pathogenic stimulus in
      molecular traits.

PMID- 24566371
TI  - Mitochondria and cytoplasmic male sterility in plants.
AB  - Mitochondria are essential organelles in cells not only because they supply over
      90% of the cell's energy but also because their dysfunction is associated with
      disease. Owing to the importance of mitochondria, there are many questions about
      mitochondria that must be answered. Cytoplasmic male sterility (CMS) is a
      mysterious natural phenomenon, and the mechanism of the origin of CMS is unknown.
      Despite successful utilization of CMS and restoration of fertility (Rf) in
      practice, the underlying mechanisms of these processes remain elusive. This
      review summarizes the genes involved in CMS and Rf, with a special focus on
      recent studies reporting the mechanisms of the CMS and Rf pathways, and concludes
      with potential working models. 

PMID- 24566372
TI  - Plant mitochondria under a variety of temperature stress conditions.
AB  - The biogenesis of plant mitochondria is a multistep process that depends on a
      concerted expression of mitochondrial and nuclear genes. The balance between
      different steps of this process, embracing various fluctuations in mitochondrial
      transcriptome and proteome, may be affected by diverse temperature treatments. A
      plethora of genes with altered expression during the acting of these stimuli were
      identified and their expression characterized, including those encoding for
      classical components of energy dissipating system. Selected aspects of current
      interest, regarding the functioning of plant mitochondria under cold and heat
      stresses, are highlighted. 

PMID- 24566373
TI  - Determination of critical assembly absolute power using post-irradiation
      activation measurement of week-lived fission products.
AB  - The work presents a detailed comparison of calculated and experimentally
      determined net peak areas of longer-living fission products after 100 h
      irradiation on a reactor with power of ~630 W and several days cooling.
      Specifically the nuclides studied are (140)Ba, (103)Ru, (131)I, (141)Ce, (95)Zr.
      The good agreement between the calculated and measured net peak areas, which is
      better than in determination using short lived (92)Sr, is reported. The
      experiment was conducted on the VVER-1000 mock-up installed on the LR-0 reactor.
      The Monte Carlo approach has been used for calculations. The influence of
      different data libraries on results of calculation is discussed as well.

PMID- 24566374
TI  - Giant magnetic anisotropy and tunnelling of the magnetization in Li2(Li(1
      x)Fe(x))N.
AB  - Large magnetic anisotropy and coercivity are key properties of functional
      magnetic materials and are generally associated with rare earth elements. Here we
      show an extreme, uniaxial magnetic anisotropy and the emergence of magnetic
      hysteresis in Li2(Li(1-x)Fe(x))N. An extrapolated, magnetic anisotropy field of
      220 T and a coercivity field of over 11 T at 2 K outperform all known hard
      ferromagnets and single-molecular magnets. Steps in the hysteresis loops and
      relaxation phenomena in striking similarity to single-molecular magnets are
      particularly pronounced for x?1 and indicate the presence of nanoscale magnetic
      centres. Quantum tunnelling, in the form of temperature-independent relaxation
      and coercivity, deviation from Arrhenius behaviour and blocking of the
      relaxation, dominates the magnetic properties up to 10 K. The simple crystal
      structure, the availability of large single crystals and the ability to vary the
      Fe concentration make Li2(Li(1-x)Fe(x))N an ideal model system to study
      macroscopic quantum effects at elevated temperatures and also a basis for novel
      functional magnetic materials.

PMID- 24566375
TI  - Detection of radioactive fragments in patients after radiological or nuclear
      emergencies using computed tomography and digital radiography.
AB  - A comparison has been carried out between standard-dose computed tomography, non
      diagnostic computed tomography and digital radiography with respect to their
      suitability for detecting radioactive fragments associated with nuclear or
      radiological events such as debris from radiological dispersal devices. The
      purpose was to investigate if radiographic imaging is justified for the detection
      and localisation of radioactive fragments in affected patients. Fragments of
      uranium (U), copper (Cu), iron (Fe) and volcanic ash with effective diameters
      ranging from (approximately) 100 to 700 MUm were selected. The fragments were
      positioned at two different locations on an anatomical torso phantom and images
      were produced with standard-dose CT, non-diagnostic CT and digital radiography.
      Capsules with radionuclides of (137)Cs, (60)Co and (99m)Tc were also positioned
      in the phantom and the effective doses were estimated for radionuclide exposures
      as well as for standard-dose CT, non-diagnostic CT and digital radiography. For
      standard-dose CT and digital radiography, U, Cu and Fe fragments were detected in
      sizes down to 100-180, 250-300 and 300-400 MUm respectively. For the non
      diagnostic CT the results were 180-250 MUm (for U), 300-400 MUm (for Cu) and 400
      500 MUm (for Fe). The effective dose from the standard-dose CT, non-diagnostic CT
      and digital radiography was 5.6, 1.9 and 0.76 mSv. Corresponding doses from
      (137)Co, (60)Co and (99m)Tc positioned at the site of fragments were in the range
      of 0.07-0.1, 0.32-0.45 and 0.08-0.09 mSv per MBq during 24 h. We conclude that,
      for a number of gamma emitters with activity levels on the order of magnitude of
      megabecquerel, imaging using ionising radiation can be justified since the
      effective dose from the radionuclides will exceed the dose from the radiological
      examination.

PMID- 24566376
TI  - Upper tract changes in patients with neurogenic bladder and sustained pressures
      >40 cm following bladder neck surgery without augmentation.
AB  - OBJECTIVE: We report new hydronephrosis or VUR (vesicoureteral reflux) in
      patients with end filling pressures >40 cm for at least 1 year after bladder neck
      surgery without augmentation for neurogenic incontinence. MATERIALS: Consecutive
      children with neurogenic sphincteric incompetency had bladder neck surgery
      without augmentation. Postoperative renal sonography and fluoroscopic urodynamics
      were done at 6 months, 12 months, and then annually. Those with sustained end
      fill pressures >40 cm for >= 1 year were included as participants in the study.
      RESULTS: Of 79 patients, 17 (22%) had end fill pressures >40 cm for at least 1
      year despite anticholinergics, with follow-up a mean of 39 months. New
      hydronephrosis or VUR developed in six (35%). All new hydronephrosis resolved
      with medical treatment, as did two out of three new VUR cases. The other patient
      with VUR had successful Dx/HA (dextranomer hyaluronic acid) injection.
      CONCLUSIONS: Despite sustained pressures >40 cm, upper tract changes developed in
      only 35% of patients, and resolved with medical management or minimally invasive
      interventions. End pressures should not be used as an independent indication for
      augmentation.

PMID- 24566377
TI  - Effect of diabetic osteoblasts on osteogenic differentiation of human umbilical
      cord mesenchymal stem cells.
AB  - BACKGROUND: This study was aimed to investigate whether osteoblasts from diabetic
      patients have a promoting effect on osteogenesis of human umbilical cord
      mesenchymal stem cells (HUMSCs). METHODS: HUMSCs were co-cultured with
      osteoblasts of diabetic and non-diabetic patients. Morphological appearance and
      cytochemical characteristics of the non-diabetic osteoblasts and diabetic
      osteoblasts were observed by hematoxylin-eosin staining, type I collagen protein
      expression, alkaline phosphatase (ALP) staining and Alizarin Red S staining. Cell
      viability, type I collagen protein expression, ALP activity and osteocalcin mRNA
      expression in HUMSCs were investigated. RESULTS: Compared with negative control
      group, the cell proliferation, type I collagen protein expression, ALP activity
      and osteocalcin mRNA were increased in HUMSCs co-cultured with diabetic and non
      diabetic osteoblasts (P<0.05). There was no statistically significant difference
      in the HUMSCs cell proliferation, type I collagen protein expression, ALP
      activity and osteocalcin mRNA between the non-diabetic and diabetic group (P
      >0.05). CONCLUSIONS: Similar to osteoblasts from non-diabetic patients,
      osteoblasts from diabetic patients also have the ability to promote HUMSCs
      proliferation, and leading to HUMSCs exhibit some characteristic of osteoblasts.

PMID- 24566378
TI  - Effect of inelastic shear stress at the interfaces in the material with a
      unidirectional fibrous structure on the SIF for a crack in the fiber and the
      energy absorbed at fiber fracture.
AB  - The paper suggests considering the presence of inelastic shear mechanisms in the
      direction of the maximum tensile stress and the absence of these mechanisms in
      the other directions as the main feature of a structural material of biological
      origin. A "cracked fiber in tube" model is used for the study of the effect of
      interface cohesive strength on the stress intensity factor (SIF) for a crack in
      the fiber and on the energy absorbed under inelastic shear at the interface of
      fibers at their fracture. The values of the cohesive strength of the interface
      between the fibers and the distance between the cracks in the fiber at which the
      maximum energy is absorbed at material fracture at the stage of the crack growth
      in the fibers are obtained. This stage precedes the pullout process of the
      completely fractured fibers. 

PMID- 24566379
TI  - Understanding mechanisms and factors related to implant fixation; a model study
      of removal torque.
AB  - Osseointegration is a prerequisite for achieving a stable long-term fixation and
      load-bearing capacity of bone anchored implants. Removal torque measurements are
      often used experimentally to evaluate the fixation of osseointegrated screw
      shaped implants. However, a detailed understanding of the way different factors
      influence the result of removal torque measurements is lacking. The present study
      aims to identify the main factors contributing to anchorage. Individual factors
      important for implant fixation were identified using a model system with an
      experimental design in which cylindrical or screw-shaped samples were embedded in
      thermosetting polymers, in order to eliminate biological variation. Within the
      limits of the present study, it is concluded that surface topography and the
      mechanical properties of the medium surrounding the implant affect the maximum
      removal torque. In addition to displaying effects individually, these factors
      demonstrate interplay between them. The rotational speed was found not to
      influence the removal torque measurements within the investigated range. 

PMID- 24566380
TI  - Computational micromechanics of bioabsorbable magnesium stents.
AB  - Magnesium alloys are a promising candidate material for an emerging generation of
      absorbable metal stents. Due to its hexagonal-close-packed lattice structure and
      tendency to undergo twinning, the deformation behaviour of magnesium is quite
      different to that of conventional stent materials, such as stainless steel 316L
      and cobalt chromium L605. In particular, magnesium exhibits asymmetric plastic
      behaviour (i.e. different yield behaviours in tension and compression) and has
      lower ductility than these conventional alloys. In the on-going development of
      absorbable metal stents it is important to assess how the unique behaviour of
      magnesium affects device performance. The mechanical behaviour of magnesium stent
      struts is investigated in this study using computational micromechanics, based on
      finite element analysis and crystal plasticity theory. The plastic deformation in
      tension and bending of textured and non-textured magnesium stent struts with
      different numbers of grains through the strut dimension is investigated. It is
      predicted that, unlike 316L and L605, the failure risk and load bearing capacity
      of magnesium stent struts during expansion is not strongly affected by the number
      of grains across the strut dimensions; however texturing, which may be introduced
      and controlled in the manufacturing process, is predicted to have a significant
      influence on these measures of strut performance. 

PMID- 24566381
TI  - Mechanical behavior of regular open-cell porous biomaterials made of diamond
      lattice unit cells.
AB  - Cellular structures with highly controlled micro-architectures are promising
      materials for orthopedic applications that require bone-substituting biomaterials
      or implants. The availability of additive manufacturing techniques has enabled
      manufacturing of biomaterials made of one or multiple types of unit cells. The
      diamond lattice unit cell is one of the relatively new types of unit cells that
      are used in manufacturing of regular porous biomaterials. As opposed to many
      other types of unit cells, there is currently no analytical solution that could
      be used for prediction of the mechanical properties of cellular structures made
      of the diamond lattice unit cells. In this paper, we present new analytical
      solutions and closed-form relationships for predicting the elastic modulus,
      Poisson's ratio, critical buckling load, and yield (plateau) stress of cellular
      structures made of the diamond lattice unit cell. The mechanical properties
      predicted using the analytical solutions are compared with those obtained using
      finite element models. A number of solid and porous titanium (Ti6Al4V) specimens
      were manufactured using selective laser melting. A series of experiments were
      then performed to determine the mechanical properties of the matrix material and
      cellular structures. The experimentally measured mechanical properties were
      compared with those obtained using analytical solutions and finite element (FE)
      models. It has been shown that, for small apparent density values, the mechanical
      properties obtained using analytical and numerical solutions are in agreement
      with each other and with experimental observations. The properties estimated
      using an analytical solution based on the Euler-Bernoulli theory markedly
      deviated from experimental results for large apparent density values. The
      mechanical properties estimated using FE models and another analytical solution
      based on the Timoshenko beam theory better matched the experimental observations.

PMID- 24566382
TI  - Time-dependent fracture toughness of cornea.
AB  - The fracture and time-dependent properties of cornea are very important for the
      development of corneal scaffolds and prostheses. However, there has been no
      systematic study of cornea fracture; time-dependent behavior of cornea has never
      been investigated in a fracture context. In this work, fracture toughness of
      cornea was characterized by trouser tear tests, and time-dependent properties of
      cornea were examined by stress-relaxation and uniaxial tensile tests. Control
      experiments were performed on a photoelastic rubber sheet. Corneal fracture
      resistance was found to be strain-rate dependent, with values ranging from 3.39+/
      0.57 to 5.40+/-0.48kJm(-2) over strain rates from 3 to 300mmmin(-1). Results from
      stress-relaxation tests confirmed that cornea is a nonlinear viscoelastic
      material. The cornea behaved closer to a viscous fluid at small strain but became
      relatively more elastic at larger strain. Although cornea properties are greatly
      dependent on time, the stress-strain responses of cornea were found to be
      insensitive to the strain rate when subjected to tensile loading. 

PMID- 24566383
TI  - Hertzian contact response and damage tolerance of dental ceramics.
AB  - OBJECTIVES: To determine the contact response and damage tolerance or strength
      degradation of a range of dental CAD/CAM ceramic materials including novel
      polymer-infiltrated-ceramic-network (PICN) materials by means of spherical
      indentations at various loads and indenter radii. METHODS: The seven tested
      materials included Mark II, PICN test materials 1 and 2, In-Ceram Alumina, VM 9,
      In-Ceram YZ (Vita Zahnfabrik, Bad Saeckingen, Germany) and IPS e.max CAD,
      (Ivoclar Vivadent, Schaan, Liechtenstein). To evaluate the damage tolerance and
      role of indenter size, indentations with tungsten carbide spheres (0.5mm and
      1.25mm radius) were placed on bending bars with varying loads (1.96-1000N). The
      indented bending bars were subsequently loaded to fracture in three-point
      bending. The contact induced damage was analyzed by light microscopy (LM) and
      SEM. The spherical contact response was measured on polished surfaces. RESULTS:
      The initial strengths for the individual materials were found to reduce above
      specific indentation loads, which were a function of the indenter radius.
      Employing a 0.5mm radius sphere resulted in the following strength degrading
      loads and ordering of materials: VM9 (98N)<MarkII-PICN1 (147N)<ICAlumina-e.maxCAD
      (300N)<PICN2-YTZP (500N). For the materials indented with the 1.25mm sphere,
      higher loads were required for the onset of strength degradation: VM9
      (190N)<MarkII (300N)<PICN1 (400N)<e.maxCAD (500N)<ICAlumina (700N)<PICN2
      (1000N)<YTZP (above 1000N). Two different damage modes were observed by SEM and
      LM - brittle cone cracking and plastic deformation. The PICN materials exhibited
      elastic-plastic behavior with creep. In contrast YTZP showed entirely elastic
      behavior upon loading with both spheres. SIGNIFICANCE: This study aims to emulate
      the likely clinical behavior of contact loading by opposing cusps to dental
      restorative ceramic materials by utilizing spherical indentations at various
      loads and sphere diameters.

PMID- 24566384
TI  - Natural history of comorbid orofacial pain among women with vestibulodynia.
AB  - OBJECTIVES: We evaluated the stability of the comorbidity between vulvodynia and
      orofacial pain (OFP) and its associated clinical characteristics over a 2-year
      follow-up period. MATERIALS AND METHODS: In an earlier study of vestibulodynia
      patients, we administered questionnaires assessing demographic data, self
      reported pain, anxiety, somatic awareness, and presence of signs and symptoms
      suggestive of clinical and subclinical OFP. The present study readministered the
      same surveys to a subset of the original cohort after a 2-year follow-up period.
      RESULTS: Of the 138 women in the previous study, 71 (51%) agreed to participate
      in the present study. We confirmed our earlier findings that (1) OFP is a highly
      prevalent (66%) condition among women with vestibulodynia, and (2) compared with
      women with no OFP symptoms, those with OFP symptoms experience higher levels of
      anxiety (P=0.005) and somatic awareness (P<0.001). Although OFP symptoms showed
      improvement in many of the vestibulodynia patients (33%) with OFP symptoms at
      baseline, 13% had either developed new symptoms or transitioned from subclinical
      to clinical OFP classification. Intercourse-related pain decreased in 69% of
      patients and increased in 24% of patients. Consistent with our earlier report, we
      did not observe significant differences with respect to demographics or severity
      of pain during intercourse among the subgroups. DISCUSSION: OFP is a common
      comorbidity among women with vestibulodynia, although the presence of OFP can
      vary over time. The comorbidity between vestibulodynia and OFP suggests that
      common underlying mechanisms may mediate both conditions.

PMID- 24566387
TI  - Increased sleep fragmentation in experimental autoimmune encephalomyelitis.
AB  - Sleep disturbance in patients with multiple sclerosis is prevalent and has
      multifactorial causes. In mice with experimental autoimmune encephalomyelitis
      (EAE), a model of multiple sclerosis, we determined the dynamic changes of sleep
      architecture and the interactions between sleep changes and EAE symptoms. The
      changes of sleep patterns were mainly reflected by altered sleep stage
      distribution and increased sleep fragmentation. Increased waking and decreased
      non-rapid eye movement sleep occurred after EAE onset and persisted through the
      symptomatic phase. There also was increased sleep state transition, indicating a
      reduction of sleep cohesiveness. Furthermore, the extent of sleep fragmentation
      correlated with the severity of disease. This is the first study of sleep
      characteristics in EAE mice demarcating specific changes related to the
      autoimmune disorder without confounding factors such as psychosocial impact and
      treatment effects. The reduction of sleep efficiency and cohesiveness supports
      the notion that enhancing sleep might facilitate the recovery of mice from EAE,
      pertinent to the multimodality treatment of multiple sclerosis. 

PMID- 24566385
TI  - In-depth conversation: spectrum and kinetics of neuroimmune afferent pathways.
AB  - Since my last review on neuroimmune communication afferents in 2008, this area
      has witnessed substantial growth. At a basic science level, numerous new and
      exciting phenomena have been described, adding both depth and complexity to the
      crosstalk between the immune system and the nervous system. At a translational
      level, accumulating evidence indicates neuroimmune interaction could be a
      contributing factor for many disease states, as well as an effective
      physiological mechanism that coordinates the activities of these two systems in
      healthy individuals or during tissue distress. Furthermore, new evidence suggests
      neuroimmune interactions are inherently dynamic: varying activities in either the
      nervous system or the immune system could impact interactions between them. In
      this review I will attempt to integrate multifarious, and sometimes disparate,
      findings into a modified conceptual framework that describes the concordance of
      neuroimmune communication through the cooperative connection between these two
      systems and the dysfunction that may arise when their inappropriate crosstalk
      occurs. 

PMID- 24566386
TI  - Maternal immune activation leads to activated inflammatory macrophages in
      offspring.
AB  - Several epidemiological studies have shown an association between infection or
      inflammation during pregnancy and increased risk of autism in the child. In
      addition, animal models have illustrated that maternal inflammation during
      gestation can cause autism-relevant behaviors in the offspring; so called
      maternal immune activation (MIA) models. More recently, permanent changes in T
      cell cytokine responses were reported in children with autism and in offspring of
      MIA mice; however, the cytokine responses of other immune cell populations have
      not been thoroughly investigated in these MIA models. Similar to changes in T
      cell function, we hypothesized that following MIA, offspring will have long-term
      changes in macrophage function. To test this theory, we utilized the poly (I:C)
      MIA mouse model in C57BL/6J mice and examined macrophage cytokine production in
      adult offspring. Pregnant dams were given either a single injection of 20mg/kg
      polyinosinic-polycytidylic acid, poly (I:C), or saline delivered
      intraperitoneally on gestational day 12.5. When offspring of poly (I:C) treated
      dams reached 10weeks of age, femurs were collected and bone marrow-derived
      macrophages were generated. Cytokine production was measured in bone marrow
      derived macrophages incubated for 24h in either growth media alone, LPS, IL
      4/LPS, or IFN-gamma/LPS. Following stimulation with LPS alone, or the combination
      of IFN-gamma/LPS, macrophages from offspring of poly (I:C) treated dams produced
      higher levels of IL-12(p40) (p<0.04) suggesting an increased M1 polarization. In
      addition, even without the presence of a polarizing cytokine or LPS stimulus,
      macrophages from offspring of poly (I:C) treated dams exhibited a higher
      production of CCL3 (p=0.05). Moreover, CCL3 levels were further increased when
      stimulated with LPS, or polarized with either IL-4/LPS or IFN-gamma/LPS (p<0.05)
      suggesting a general increase in production of this chemokine. Collectively,
      these data suggest that MIA can produce lasting changes in macrophage function
      that are sustained into adulthood. 

PMID- 24566388
TI  - The essential role of TNIK gene amplification in gastric cancer growth.
AB  - Traf2- and Nck-interacting kinase (TNIK) is one of the germinal center kinase
      family members involved in cytoskeleton organization and neuronal dendrite
      extension. Emerging evidence supports that TNIK is essential for activation of
      WNT signaling pathway in colon cancer growth. To search for novel genetic
      aberrations that drive carcinogenesis, we performed microarray-based comparative
      hybridization assay for gene copy number variations in primary tumor samples. Our
      data showed that TNIK gene was amplified in 7% (8/106) of Chinese gastric cancer
      patients. Theses amplifications were confirmed by fluorescence in situ
      hybridization analysis. PAMC82 human gastric cancer and T47D human breast cancer
      cell lines with TNIK amplification were identified to further understand the
      function of TNIK gene amplification. RNA-interference-mediated silencing of TNIK
      resulted in significant inhibition of cell growth and induction of cell death in
      TNIK-amplified, but not in TNIK-non-amplified, cell lines tested. This selective
      sensitivity to the TNIK inhibition was also observed under the effect of a small
      molecule TNIK inhibitor. Furthermore, our data indicated that TNIK's role in
      gastric cancer growth was not dependent on Wnt signaling but rather was involved
      in AKT activation and cell autophagy. Together, our results suggest that TNIK is
      a novel therapeutic target in gastric cancer and TNIK amplification can be
      potentially used for patient selection. 

PMID- 24566389
TI  - Adulteration of Ginkgo biloba products and a simple method to improve its
      detection.
AB  - Extracts of ginkgo (Ginkgo biloba) leaf are widely available worldwide in herbal
      medicinal products, dietary supplements, botanicals and complementary medicines,
      and several pharmacopoeias contain monographs for ginkgo leaf, leaf extract and
      finished products. Being a high-value botanical commodity, ginkgo extracts may be
      the subject of economically motivated adulteration. We analysed eight ginkgo leaf
      retail products purchased in Australia and Denmark and found compelling evidence
      of adulteration with flavonol aglycones in three of these. The same three
      products also contained genistein, an isoflavone that does not occur in ginkgo
      leaf. Although the United States Pharmacopeia - National Formulary (USP-NF) and
      the British and European Pharmacopoeias stipulate a required range for flavonol
      glycosides in ginkgo extract, the prescribed assays quantify flavonol aglycones.
      This means that these pharmacopoeial methods are not capable of detecting
      adulteration of ginkgo extract with free flavonol aglycones. We propose a simple
      modification of the USP-NF method that addresses this problem: by assaying for
      flavonol aglycones pre and post hydrolysis the content of flavonol glycosides can
      be accurately estimated via a simple calculation. We also recommend a maximum
      limit be set for free flavonol aglycones in ginkgo extract. 

PMID- 24566391
TI  - Role of plaque calcification regulators osteoprotegerin and matrix Gla-proteins
      in stable angina and acute myocardial infarction.
AB  - AIM: To assess serum levels of the plaque calcification regulators
      osteoprotegerin (OPG) and Matrix Gla-proteins (MGP) in individuals with stable
      angina and acute myocardial infarction submitted to coronary angiography and
      their relation to coronary artery disease burden. METHODS: The study included 40
      individuals affected by ST-elevation myocardial infarction (STEMI) and 40
      individuals with stable angina who all underwent coronary angiography, with
      evaluation of the extent of coronary artery disease by Syntax Score calculation
      and measurement of serum OPG and MGP levels. Osteoporosis was excluded by femoral
      and vertebral computerized bone mineralometry. RESULTS: Serum OPG and MGP levels
      were respectively 3.87 +/- 1.07 pmol/l and 6.80 +/- 2.43 nmol/l in the stable
      angina group, 7.57 +/- 1.5 pmol/l and 7.18 +/- 1.93 nmol/l in the STEMI group (P
      < 0.01 and P = 0.33, respectively). Pearson correlation coefficient for OPG and
      Syntax Score, MGP and Syntax score was respectively 0.79 (P < 0.01) and 0.18 (P =
      0.22) in the stable angina group, -0.03 (P = 0.43) and 0.10 (P = 0.5) in the
      STEMI group.Serum OPG and MGP levels were respectively 5.52 +/- 1.02 pmol/l and
      7.56 +/- 1.42 nmol/l in diabetics, 4.3 +/- 0.8 pmol/l and 6.52 +/- 1.14 nmol/l in
      nondiabetics (P < 0.05; P < 0.05). CONCLUSION: OPG, in a relatively small group
      of patients with stable angina, correlates proportionally with the extent of
      coronary artery disease (CAD), as evaluated by the Syntax Score. Higher serum OPG
      levels can be observed in individuals with STEMI regardless of CAD burden. As for
      MGP, a potential role as marker of plaque calcification remains unproven.

PMID- 24566390
TI  - Histamine H3 receptors aggravate cerebral ischaemic injury by histamine
      independent mechanisms.
AB  - The role of the histamine H3 receptor (H3R) in cerebral ischaemia/reperfusion
      (I/R) injury remains unknown. Here we show that H3R expression is upregulated
      after I/R in two mouse models. H3R antagonists and H3R knockout attenuate I/R
      injury, which is reversed by an H3R-selective agonist. Interestingly, H1R and H2R
      antagonists, a histidine decarboxylase (HDC) inhibitor and HDC knockout all fail
      to compromise the protection by H3R blockade. H3R blockade inhibits mTOR
      phosphorylation and reinforces autophagy. The neuroprotection by H3R antagonism
      is reversed by 3-methyladenine and siRNA for Atg7, and is diminished in Atg5-/-
      mouse embryonic fibroblasts. Furthermore, the peptide Tat-H3R(CT414-436), which
      blocks CLIC4 binding with H3Rs, or siRNA for CLIC4, further increases I/R-induced
      autophagy and protects against I/R injury. Therefore, H3R promotes I/R injury
      while its antagonism protects against ischaemic injury via histamine-independent
      mechanisms that involve suppressing H3R/CLIC4 binding-activated autophagy,
      suggesting that H3R inhibition is a therapeutic target for cerebral ischaemia.

PMID- 24566393
TI  - Hypoxia, not hypercapnia, induces cardiorespiratory failure in rats.
AB  - Mechanical respiratory loads induce cardiorespiratory failure, presumably by
      increasing O2 demand concurrently with decreases in O2 availability (decreased
      PaO2). We tested the hypothesis that asphyxia alone can cause cardiorespiratory
      failure ("failure") in pentobarbital-anesthetized rats. We also tested the
      hypothesis that hypoxia, not hypercapnia, is responsible by supplying
      supplemental O2 during mechanical loading in a separate group of rats. Asphyxia
      (mean PaO2 and PaCO2 of 43 and 69mmHg, respectively) resulted in failure, evident
      as a slowing of mean respiratory frequency (133-83breaths/min) and a sudden and
      large drop in mean arterial pressure (71-47mmHg), after 214+/-66min (n=16; range
      117-355min). Neither respiratory drive nor heart rate decreased, indicating that
      failure was peripheral, not central. Of 8 rats tested after 3h of asphyxia for
      the presence in blood of cardiac troponin T, all were positive. In an additional
      6 rats, normocapnic hypoxia (mean PaCO2 and PaO2 were 39+/-2.2 and 41+/-3.1mmHg,
      respectively) caused failure after an average 205min (range 181-275min), no
      different from that of asphyxic rats. In the 6 rats that breathed O2 during an
      initially moderate inspiratory resistive load, endurances exceeded 7h (failure
      occurring only because we increased the load after 6h) and tracheal pressure and
      left ventricular dP/dt were maintained despite supercarbia (PaCO2>150mmHg). Thus,
      asphyxia alone can induce failure, the failure is due to hypoxia, not
      hypercapnia, and hypercapnia has minimal effects on cardiac and respiratory
      muscle function in the presence of hyperoxia. 

PMID- 24566394
TI  - Inflammatory myofibroblastic tumor mimicking gastric gastrointestinal stromal
      tumor on 18F-FDG PET/CT.
AB  - A 59-year-old man underwent abdominal CT for evaluation of weight loss and
      generalized weakness. A large mass protruding from the lesser curvature of the
      stomach suggestive of gastrointestinal stromal tumor was demonstrated. F-FDG
      PET/CT showed hypermetabolic activity in the gastric mass. Mass excision and
      wedge resection were performed, and the diagnosis of inflammatory myofibroblastic
      tumor was confirmed. 

PMID- 24566392
TI  - Learning to breathe: habituation of Hering-Breuer inflation reflex emerges with
      postnatal brainstem maturation.
AB  - The Hering-Breuer (HBR) reflex is considered a major regulatory feedback for the
      generation and patterning of respiratory activity. While HBR is important in
      neonates, its significance in adults is controversial. Previous experiments that
      investigated the plasticity of entrainment of the respiratory rhythm by vagal
      input demonstrated postnatal changes in HBR plasticity. Here we analyzed
      postnatal changes in the plasticity of HBR by mimicking the classic lung
      inflation tests with repetitive tonic vagal stimulation across different
      postnatal stages in an in situ perfused brainstem preparation of rat. The study
      shows that neonates stereotypically exhibit HBR stimulus-dependent prolongation
      of expiration while juvenile preparations (>postnatal day 16) showed significant
      habituation of HBR following repetitive stimulation. Subsequent experiments
      employing physiological lung inflation tests in situ confirmed HBR habituation in
      juveniles. We conclude that postnatal emergence of HBR habituation explains the
      weak contribution and high activation threshold of HBR in the regulation of
      eupnea. 

PMID- 24566395
TI  - Serial FDG PET/CT in autoimmune encephalitis with faciobrachial dystonic
      seizures.
AB  - Autoimmune encephalitis (AE) is increasingly recognized as a nonparaneoplastic
      disorder with autoantibodies to neuronal proteins. Although MRI is frequently
      unremarkable, PET imaging might contribute to identification of affected brain
      regions in distinct AE. We report on serial FDG PET in a 72-year-old man with
      particular AE subtype, with potassium channel complex antibodies and prodromal
      stage with dystonic seizures. Serial FDG PET/CT revealed that besides limbic
      structures, basal ganglia are centrally involved and presumably play a key role
      in the generation of dystonic seizures. 

PMID- 24566396
TI  - Neuronal correlates of clinical asymmetry in progressive supranuclear palsy.
AB  - PURPOSE: Progressive supranuclear palsy (PSP) is characterized by a symmetric
      hypokinetic syndrome with early falls and vertical supranuclear gaze palsy.
      However, clinically asymmetric manifestations occur, resembling idiopathic
      Parkinson disease or corticobasal degeneration. The aim of this study was to
      determine the neuronal correlates of patients suffering from PSP with a
      lateralized disease manifestation (hemi-PSP) in comparison to patients with
      symmetric clinical presentation (symPSP) and corticobasal degeneration. METHODS:
      Twenty-three patients with PSP and 8 patients with corticobasal degeneration
      according to standard diagnostic criteria underwent F-fluorodeoxyglucose (FDG)
      PET scans to assess disease-specific patterns of regional cerebral glucose
      metabolism reflecting neuronal activity. Group differences were analyzed by
      statistical parametric mapping and region-of-interest analyses. RESULTS:
      Clinically, 14 patients presented with symPSP while 9 patients were considered as
      hemi-PSP. Patients with symPSP or hemi-PSP showed similar bilateral medial
      frontal hypometabolism compared to corticobasal degeneration patients. In
      contrast, corticobasal degeneration patients exhibited a prominent parietal
      hypometabolism compared to both symPSP and hemi-PSP patients. SymPSP patients
      showed no significant hypometabolism compared to hemi-PSP, whereas hemi-PSP
      patients presented with significant hypometabolism of the motor thalamus, middle
      cingulate gyrus, and sensorimotor cortex contralateral to the most affected body
      side compared to symPSP patients. CONCLUSIONS: The present study demonstrates
      that a more pronounced and asymmetric involvement of cortical and subcortical
      motor areas is associated with a lateralized disease manifestation of PSP.
      Furthermore, these findings strongly suggest that FDG PET imaging may assist the
      challenging clinical differentiation between hemi-PSP and corticobasal
      degeneration by depicting disease-specific patterns of regional cerebral glucose
      metabolism.

PMID- 24566397
TI  - In vivo and in vitro evidence of somatostatin receptors expression in a
      dedifferentiated retroperitoneal liposarcoma.
AB  - A 62-year-old patient presented with mildly elevated catecholamines and an
      abdominal painless mass. Abdominal CT revealed an 18 * 12 cm tumor in the right
      retroperitoneum with intense contrast enhancement. Somatostatin receptor
      scintigraphy (SRS) showed pathologic uptake by the lesion. Given the suspicion of
      paraganglioma, the patient was referred to surgery for tumor removal.
      Surprisingly, the histopathological examination revealed a dedifferentiated
      liposarcoma. Somatostatin receptors of type 2 were identified and quantified by
      reverse transcription polymerase chain reaction. The unexpected presentation of
      our patient draws clinicians' attention when performing diagnostic procedure for
      retroperitoneal lesions, even though hormone secretion and positive SRS strongly
      suggest paraganglioma. 

PMID- 24566398
TI  - Paget sarcoma of the pelvic bone with widespread metastatic disease on
      radiography, CT, MRI, and 18F-FDG PET/CT with pathologic correlation.
AB  - We report a case of Paget sarcoma of the left superior pubic ramus and
      disseminated metastatic disease in a 70-year-old man. Paget disease of the left
      hemipelvis with malignant degeneration in the region of the left superior pubic
      ramus was initially diagnosed on radiographs. Subsequent CT, MRI, PET/CT imaging,
      and CT-guided biopsy confirmed the diagnosis and showed extensive left-sided
      pelvic and abdominal lymphadenopathy with widespread metastatic disease to liver,
      spleen, and lungs. 

PMID- 24566399
TI  - Lymphoma and tuberculosis: temporal evolution of dual pathology on sequential 18F
      FDG PET/CT.
AB  - Tuberculosis can often be seen in patients undergoing chemotherapy for lymphoma,
      especially in endemic countries. As both tuberculosis and lymphoma can lead to
      hypermetabolic lesions of F-FDG PET/CT, a diagnostic dilemma often ensues. We
      present the sequential F-FDG PET/CT images of a 22-year-old female patient with
      Hodgkin lymphoma who developed tuberculosis and later relapse of lymphoma. These
      images present the temporal evaluation of the dual pathology on F-FDG PET/CT. 

PMID- 24566400
TI  - Focal splenic FDG uptake in a patient with Kala-Azar (visceral leishmaniasis).
AB  - We present a woman with a history of Gaucher disease and secondary portal
      hypertension. She went to hospital for treatment of resistant fever without
      apparent cause. A conventional study of fever of unknown origin did not show any
      pathology. For this reason, she was referred to our department for a PET/CT,
      which did not demonstrate a cause for the fever. Two months after, she was
      admitted again in hospital for fever recurrence. A new PET/CT showed FDG avid
      hypodense splenic lesions, suspicious for infection. Splenectomy was performed
      and histopathologic analysis demonstrated intracellular organisms compatible with
      Leishmania. 

PMID- 24566401
TI  - 18F-FDG PET/CT superscan in prostate cancer.
AB  - F-FDG PET/CT of a patient with inflammatory lower back pain reveals diffuse bony
      metastases, similar to the "superscan" found on a Tc-methylene diphosphonate
      scintigraphy, and also demonstrates a prostatic lesion which appears to be a
      poorly differentiated prostate adenocarcinoma. 

PMID- 24566402
TI  - 18FDG PET/CT findings in the unusual urachal adenocarcinoma.
AB  - A 48-year-old woman presented with a hard, painless mass in the left lower
      quadrant and no other significant complaint. Laboratory tests, including those
      for tumor markers, showed no significant abnormal value. CT showed an
      extraperitoneal mixed solid and cystic mass in the anterior abdominal wall,
      located anterocranial to and in close contact with the bladder. Percutaneous
      biopsy findings were compatible with adenocarcinoma of unknown origin. PET/CT
      showed increased 18FDG uptake on the mass and no evidence of disease at other
      sites. The patient underwent tumor resection, and the pathological diagnosis was
      moderately differentiated urachal adenocarcinoma.

PMID- 24566403
TI  - Diuretic 68Ga DOTANOC PET/CT in imaging of bladder paraganglioma.
AB  - Urinary bladder paragangliomas are exceedingly rare tumors. A 22-year-old woman
      with bladder paraganglioma underwent Ga DOTANOC PET/CT for proper localization of
      the primary tumor and to rule out locoregional and distant metastases. Ga DOTANOC
      avid bladder mass was detected with no other abnormal site of radiotracer uptake
      elsewhere. Although radioactive urine can mask urinary paragangliomas, diuretic
      method can aid tumor detection by Ga DOTANOC PET/CT. 

PMID- 24566404
TI  - Ivory vertebra on 18F-sodium fluoride scan: an old sign in a new modality.
AB  - We report a case of ivory vertebra on 18F-sodium fluoride. A prostate cancer
      patient had a 18F-sodium fluoride PET scan to evaluate overall spread of disease.
      In addition to other findings of metastatic disease, the patient had an ivory
      vertebra.

PMID- 24566405
TI  - Appearance of extraosseous pelvic Ewing sarcoma on triphasic bone scan.
AB  - A 24-year-old man with extraosseous Ewing sarcoma in the pelvis underwent a
      triphasic bone scintigraphy to rule out bone metastases and local bone
      infiltration before chemotherapy. The bone scintigraphy showed tracer uptake in
      the tumor in all 3 phases. 

PMID- 24566406
TI  - Asymptomatic solitary cerebral metastasis from papillary carcinoma thyroid: 131I
      SPECT/CT for accurate staging.
AB  - Isolated asymptomatic brain metastasis in papillary carcinoma thyroid (PCT) is
      extremely rare. We here present such a case of a 48-year-old woman with PCT.
      SPECT/CT localized the 131I radiotracer concentration seen on whole-body scan in
      this patient to the right posterior parietal cortex, suggesting brain metastasis.
      Contrast-enhanced MRI and 18F-FDG PET/CT confirmed the diagnosis and the patient
      was taken for gamma-knife radiosurgery. 131I SPECT/CT in this case accurately
      restaged the patient by detecting asymptomatic isolated brain metastasis and
      correctly directed the management strategy.

PMID- 24566407
TI  - 68Ga DOTANOC PET/CT in primary neuroendocrine tumor of the breast.
AB  - Primary neuroendocrine tumor (NET) of the breast is very rare. We present a case
      of a pathologically confirmed, primary breast NET in a 49-year-old woman with
      68Ga DOTANOC PET/CT imaging findings. 68Ga DOTANOC PET/CT revealed somatostatin
      receptors expressing active lesions in primary right breast NET with metastases
      to multiple bilateral axillary and right cervical lymph nodes, bilateral lungs,
      and multiple skeletal sites.

PMID- 24566408
TI  - Lower incidence of postpartum thyrotoxicosis in women with Graves disease treated
      by radioiodine therapy than by subtotal thyroidectomy or with antithyroid drugs.
AB  - PURPOSE OF THE REPORT: The incidence of postpartum thyrotoxicosis (PT) in Graves
      disease (GD) patients treated with antithyroid drugs (ATDs) is higher than in the
      general population, but the incidence of PT among GD patients who had been
      treated with radioiodine (RI) or by subtotal thyroidectomy before their pregnancy
      is not well known. SUBJECTS AND METHODS: We reviewed the cases of women with GD
      who had become pregnant, and we selected the 188 women who had undergone RI
      therapy before the pregnancy and the 148 women who had undergone subtotal
      thyroidectomy for GD before the pregnancy as the subjects of this study. The ATD
      subjects were 107 women with GD who had become pregnant after being treated with
      ATDs alone before their pregnancy and were in remission before and throughout the
      pregnancy. RESULTS: The overall incidence of PT was 2.1% (4/188) in the RI group,
      23.6% (35/148) in the subtotal thyroidectomy group, and 55.1% (59/107) in the ATD
      group. There were no cases of permanent thyrotoxicosis in the RI group.
      CONCLUSIONS: The incidence of PT among women with GD who have undergone RI
      therapy before their pregnancy was significantly low compared to thyroidectomy
      group and ATD group. This finding is interesting because the incidence of PT in
      the RI group was lower than subtotal thyroidectomy group even though thyroid
      volume had been greatly reduced by thyroidectomy. RI treatment is recommended in
      the choice of treatment for childbearing-age women as regards the risk of
      postpartum recurrence.

PMID- 24566409
TI  - Restaging clear cell renal carcinoma with 18F-FDG PET/CT.
AB  - AIM: The aim of our retrospective study was to assess the usefulness of F-FDG
      PET/CT in the restaging of clear cell renal cell carcinoma (RCC) patients.
      PATIENTS AND METHODS: Sixty-nine patients (median age = 62 years; range = 36-86
      years) affected by clear cell RCC (TNM at staging: T1, 42 patients; T2, 13
      patients; T3, 11 patients; T4, 3 patients; Fuhrman grade: G2, 47 patients; G3, 20
      patients; G4, 2 patients) underwent whole-body F-FDG PET/CT to restage the
      disease after nephrectomy for clinical or radiological suspicion of metastases.
      Areas of abnormal uptake at PET/CT were classified, taking the liver uptake as
      reference, as follows: 1 = faint uptake, lower than liver; 2 = moderate uptake,
      equal to liver; and 3 = high uptake, higher than liver. Validation of F-FDG
      PET/CT results was established by (1) biopsy (23 patients) and (2) other imaging
      modalities (addressed BS; c.e.CT; MRI; F-fluoride PET/CT; subsequent F-FDG
      PET/CT), and/or clinical and radiological follow-up of 12 months (46 patients).
      RESULTS: F-FDG PET/CT was positive in 42 patients and negative in 27 patients.
      Sixteen patients presented single lesions and 26 patients presented multiple
      localizations of the disease. On a patient basis, 40 patients resulted true
      positive, 2 patient false positive, 23 patients true negative, and 4 patients
      false negative. Sensitivity, specificity, accuracy, positive predictive value,
      and negative predictive value were 90%, 92%, 91%, 95%, and 85%, respectively. On
      a lesion basis, PET/CT detected 114 areas of abnormal uptake in 42 positive
      patients of which 112 resulted to be true positive. FDG uptake of the true
      positive lesions resulted to be high in 83 cases, moderate in 17 lesions, and
      finally faint in 12 lesions. CONCLUSIONS: F-FDG PET/CT demonstrated a good
      sensitivity in the restaging of clear cell RCC. Most of the lesions showed
      intense activity. According to our results, it seems that the use of F-FDG PET/CT
      in the restaging of RCC is feasible because the number of false-negative cases is
      limited.

PMID- 24566410
TI  - 18F NaF brain metastasis uptake in a patient with melanoma.
AB  - A 57-year-old man with a history of metastatic melanoma and sclerotic bone
      lesions seen on CT was referred for F NaF PET/CT evaluation of active skeletal
      metastases. While the bone lesions had no uptake and were therefore thought to
      represent sequela of previously treated disease, an unexpected area of F NaF
      uptake was identified in the left temporal lobe. Concurrent contrast-enhanced
      brain MRI re-demonstrated a large metastasis, also seen on previous MRI scans
      done at another institution. 

PMID- 24566411
TI  - 18F-DOPA, a clinically available PET tracer to study brain inflammation?
AB  - We report 2 cases of suspected low-grade glioma with positive 18F
      fluorodihydroxyphenylalanine (18F-FDOPA) PET scan, and histological diagnosis of
      brain inflammation corresponding to an acute disseminated encephalomyelitis
      (ADEM) and to a neurosarcoidosis. It has been shown that this amino-acid PET
      radiotracer serves to evaluate tumoral proliferation related to the metabolism of
      L-amino-acid transporters, and that inflammation may also contribute to the
      tumoral uptake. This report suggests it may serve to study brain inflammation.

PMID- 24566412
TI  - A large pelvic soft tissue mass implied by subtle bone scan findings.
AB  - An 18-year-old man with alveolar rhabdomyosarcoma and osseous metastases
      underwent bone scintigraphy to monitor the effect of chemotherapy. The images
      showed significant improvement of bone lesions. However, the scan revealed a
      vertically shaped urinary bladder and diffused increased activity in the genital
      region. A diagnostic pelvic CT was subsequently performed, which showed a
      thickened bladder wall, an ill-defined pelvic mass, and extensive subcutaneous
      edema in the genital region. 

PMID- 24566413
TI  - Tips for a physician in getting the right job, part x: preparation and
      appearance.
AB  - Preparation for a job interview is very helpful in building up the applicant's
      self-confidence and having the interview go well. One aspect of interviewing is
      the appearance of the applicant. Appearance is a very important factor in the
      overall impression the candidate makes on the interviewers. This article gives a
      number of pointers about preparation and discusses the subject of interviewee
      appearance in depth. 

PMID- 24566414
TI  - Isolated nasal tip metastasis from esophageal squamous cell carcinoma.
AB  - Cutaneous metastatic tumors to the nasal tip are very rare. A 74-year-old woman
      presented with progressive dysphagia for 4 months and a painless red violaceous
      nodule in the nasal tip for the last 6 weeks. Gastroendoscopy showed
      midesophageal wall thickening, which corresponded to esophageal squamous cell
      carcinoma confirmed by endoscopic biopsy. F-FDG PET/CT showed intense FDG uptake
      of the esophageal carcinoma (SUVmax, 19.0) and the nasal tip nodule (SUVmax,
      29.1). The patient underwent biopsy of the nasal tip nodule. Nasal tip metastasis
      from the esophageal squamous cell carcinoma was confirmed by pathologic
      examination. 

PMID- 24566415
TI  - Crossed cerebellar hypermetabolism demonstrated by FDG PET.
AB  - Crossed cerebellar hypometabolism on 18F-FDG PET has been well described.
      However, crossed cerebellar hypermetabolism is rare. We described a case of
      crossed cerebellar hypermetabolism in a middle-aged woman. The patient underwent
      FDG PET to assess epileptogenic focus during her subclinical seizure episode,
      which was shown on video electroencephalography. The crossed cerebellar
      hypermetabolism was no longer visualized when her subclinical seizure was
      controlled.

PMID- 24566416
TI  - Proposal of a new acquisition protocol for bladder cancer visualization with 18F
      FDG PET/CT.
AB  - F-FDG PET/CT has a limited role in the evaluation of locoregional bladder cancer
      because of the interference of radioactive urine. Methods proposed to overcome
      interference are based on F-FDG washout and include late images after voiding,
      catheterization, bladder irrigation, and forced diuresis. We performed a very
      early F-FDG PET/CT acquisition of the pelvic region in a man with bladder cancer
      with wall invasion in order to evaluate the feasibility and usefulness of this
      method to visualize bladder cancer. Early images revealed a pathologic
      accumulation of the tracer in the posterior left wall of the bladder that was
      thickened on the CT images. 

PMID- 24566417
TI  - Increased 131I accumulation in the polyacrylamide hydrophilic gel used for breast
      augmentation.
AB  - A 37-year-old woman with papillary thyroid cancer received repeat 131I therapy.
      The first posttherapy scan revealed only activity in the neck. However, both the
      second and third posttherapy scans showed intense activity in the anterior lower
      chest bilaterally, suggestive of breast uptake. However, the SPECT/CT images
      demonstrated that the iodine activity was not located in the breast tissue.
      Instead, the activity was inside the polyacrylamide hydrophilic gels she received
      10 years ago for breast augmentation.

PMID- 24566418
TI  - Double tongues.
AB  - A 1-year-old Chinese boy presented with a mass at the base of his tongue with
      dysphagia. The distal end of the lesion could be put out of his mouth, making a
      "double tongue" appearance. Before surgery, serum test showed euthyroidism.
      Thyroid scintigraphy showed good function of the orthotopic thyroid, yet no
      uptake by the lesion, excluding ectopic thyroid. En bloc resection was performed.
      Histopathology demonstrated aberrant salivary tissues. Our case indicates that
      differential diagnosis between ectopic salivary tissues and ectopic thyroid
      should be borne in mind when treating patients with double tongues. 

PMID- 24566419
TI  - Follicular thyroid carcinoma metastasis to the internal jugular vein demonstrated
      by 131I SPECT/CT.
AB  - Cervical uptake detected by 131I whole body scintigraphy (131I-WBS) may be due to
      thyroid remnants or loco-regional metastases. We describe a patient with
      follicular carcinoma submitted to total thyroidectomy. 131I-WBS showed left
      cervical linear uptake and focal areas of uptake in the abdomen and pelvis.
      SPECT/CT images demonstrated a potential thrombus in the left jugular vein
      (confirmed by doppler neck ultrasound and MRI) as well as bone metastases. The
      patient was submitted to thrombectomy and histopathology confirmed metastasis of
      follicular carcinoma.

PMID- 24566420
TI  - Pericardial mucinous adenocarcinoma on 18F-FDG PET/CT.
AB  - A 56-year-old woman presented a history of left chest discomfort for 6 months. A
      prior CT revealed pericardial thickening, and malignancy cannot be excluded. For
      this reason, an FDG PET/CT scan was performed, which revealed abnormal activity
      inside the pericardium. The pathologic examination results after surgery
      demonstrated a mucinous adenocarcinoma. 

PMID- 24566421
TI  - Prenatal Bisphenol A exposure delays the development of the male rat mammary
      gland.
AB  - Our aims were to evaluate whether exposure to Bisphenol A (BPA) modifies the
      development of the male rat mammary gland (MG) and to evaluate whether this
      modification is gender specific. From gestational day 9, pregnant rats were
      exposed either subcutaneously to 0, 25 or 250MUg BPA/kgbw/day until parturition
      or orally to 0 and 64MUg BPA/kgbw/day until weaning. MG development was analyzed
      on postnatal days (PND) 5, 15 and 30. On PND30, steroid hormone receptor
      expression and mammary growth were also evaluated. On PND30, the exposure to
      64BPA and 250BPA induced a delay in male MG development, evidenced by reduced
      ductal growth, decreased number of terminal structures and lower expression of
      androgen receptor (AR). In contrast, female mammary ductal growth was altered
      only by 250BPA. Regardless of the administration route and length of the exposure
      period, BPA induced a delay in MG development and modified AR expression in
      prepubertal male rats. 

PMID- 24566424
TI  - Drugs for type 2 diabetes.

PMID- 24566422
TI  - Evolution of sexually dimorphic longevity in humans.
AB  - Why do humans live longer than other higher primates? Why do women live longer
      than men? What is the significance of the menopause? Answers to these questions
      may be sought by reference to the mechanisms by which human aging might have
      evolved. Here, an evolutionary hypothesis is presented that could answer all
      three questions, based on the following suppositions. First, that the evolution
      of increased human longevity was driven by increased late-life reproduction by
      men in polygynous primordial societies. Second, that the lack of a corresponding
      increase in female reproductive lifespan reflects evolutionary constraint on late
      life oocyte production. Third, that antagonistic pleiotropy acting on androgen
      generated secondary sexual characteristics in men increased reproductive success
      earlier in life, but shortened lifespan. That the gender gap in aging is
      attributable to androgens appears more likely given a recent report of
      exceptional longevity in eunuchs. Yet androgen depletion therapy, now used to
      treat prostatic hyperplasia, appears to accelerate other aspects of aging (e.g.
      cardiovascular disease). One possibility is that low levels of androgens
      throughout life reduces aging rate, but late-life androgen depletion does not. 

PMID- 24566423
TI  - Ursolic acid and its natural derivative corosolic acid suppress the proliferation
      of APC-mutated colon cancer cells through promotion of beta-catenin degradation.
AB  - Ursolic acid (UA) and corosolic acid (CA), naturally occurring pentacyclic
      triterpene acids, exhibit antiproliferative activities against various cancer
      cells, but a clear chemopreventive mechanism of these triterpenoids in colon
      cancer cells remains to be answered. Here we used a cell-based reporter system
      for detection of beta-catenin response transcription (CRT) to identify UA as an
      antagonist of the Wnt/beta-catenin pathway. UA promoted the degradation of
      intracellular beta-catenin that was accompanied by its N-terminal phosphorylation
      at Ser33/37/Thr41 residues, marking it for proteasomal degradation. Consistently,
      UA down-regulated the intracellular beta-catenin level in colon cancer cells with
      inactivating mutations of adenomatous polyposis coli (APC). In addition, UA
      repressed the expression of beta-catenin/T-cell factor (TCF)-dependent genes,
      thereby inhibiting cell proliferation in colon cancer cells. The functional group
      analysis revealed that the major structural requirements for UA-mediated beta
      catenin degradation are a carboxyl group at position 17 and a methyl group at
      position 19. Notably, CA (2alpha-hydroxyursolic acid) was also found to decrease
      the level of intracellular beta-catenin and to suppress the growth of APC-mutated
      colon cancer cells. Our findings suggest that UA and CA exert their anticancer
      activities against colon cancer cells by promoting the N-terminal phosphorylation
      and subsequent proteasomal degradation of beta-catenin. 

PMID- 24566425
TI  - Mesh fistulation into the rectum after laparoscopic ventral mesh rectopexy.
AB  - INTRODUCTION: Laparoscopic ventral mesh rectopexy (LVMR) is an effective method
      of management of functional disorders of the rectum including symptomatic rectal
      intussusception, and obstructed defaecation. Despite the technical demands of the
      procedure and common use of foreign body (mesh), the incidence of mesh related
      severe complications of the rectum is very low. PRESENTATION OF CASE: A 63 year
      old woman presented with recurrent pelvic sepsis following a mesh rectopexy.
      Investigations revealed fistulation of the mesh into the rectum. She was treated
      with an anterior resection. DISCUSSION: The intraoperative findings and
      management of the complication are described. Risk factors for mesh attrition and
      fistulation are also discussed. CONCLUSION: Chronic sepsis may lead to 'late'
      fistulation after mesh rectopexy.

PMID- 24566426
TI  - Upper cervical spinal cord gunshot injury without bone destruction.
AB  - INTRODUCTION: This report describes a rare case of the gunshot injury of the
      spine and spinal cord. PRESENTATION OF CASE: A rare case of the bullet lodged
      intra-durally in the upper cervical region without damaging the vertebrae or the
      spinal cord. The bullet was removed as microneurosurgical and duraplasty was
      performed. DISCUSSION: Surgical management of the gunshot wounds of the spine and
      spinal cord is not widely advocated and controversial. CONCLUSION: Advances in
      microneurosurgical instrumentation and microscopic techniques may open up a new
      era of surgical treatment of spinal cord gunshot wounds.

PMID- 24566427
TI  - Schistosomiasis as a rare cause of recurrent acute appendicitis - A case report.
AB  - INTRODUCTION: We are presenting a case of schistosomiasis in a 41 year old lady
      who presented with right iliac fossa pain for 3 years. The pain worsened and the
      frequency increased in the last 3 months prior to referral. The ultrasound was
      unremarkable. Her bowel habits were normal and there was no vomiting. There was
      no blood in the stool or in the urine. PRESENTATION OF CASE: The abdomen was soft
      except on deep palpation. There was slight tenderness in the right lower
      quadrant. A repeat ultrasound was unremarkable. The full blood count was within
      the normal range. A diagnosis of recurrent acute appendicitis was made and an
      interval appendicectomy was performed. DISCUSSION: Histopathology results
      revealed schistosomiasis of the appendix. There was no acute inflammation but
      there was fibrous obliteration of the distal lumen of the appendix and reactive
      lymphoid hyperplasia. CONCLUSION: This is the first case in a country with
      relatively clean drinking water. There are no irrigation schemes but there are
      seasonal rivers and streams. The patient admits to swimming in these streams
      during childhood. Clinical features of schistosomiasis were not elicited.

PMID- 24566428
TI  - Pedicled omental and split skin graft in the reconstruction of the anterior
      abdominal wall.
AB  - INTRODUCTION: The POSSG is a pedicled graft based on either the right or left
      gastro-epiploic arteries. It is used with a dual mesh in reconstruction of full
      thickness defects of anterior abdominal wall and covered by skin grafts.
      PRESENTATION OF CASE: A recurrent malignant peripheral nerve sheath tumor (MPNST)
      of the anterior abdominal wall was excised leaving a large defect. The POSSG was
      used for reconstruction. A large dual mesh was placed to close the defect in the
      abdominal wall by suturing it to the remnant rim of abdominal muscles. The
      omental pedicle was brought through a keyhole in the mesh, spread out over the
      mesh, sutured and covered by split skin grafts. The final graft take was 90
      percent. DISCUSSION: The POSSG can be used to reconstruct any size of anterior
      abdominal wall defects due to the malleable nature of omentum. Its prerequisite
      however is a dual mesh like PROCEED. The POSSG helps keep the more complex
      musculofasciocutaneous flaps as lifeboats. It can be used singly where multiple
      musculofasciocutaneous flaps would otherwise have been required. It can be used
      in patients with poor prognosis of underlying malignancy. It may be used by
      general surgeons due to familiarity with anatomy of the relevant structures and
      lack of need for microsurgical skill. CONCLUSION: The POSSG can be used in
      reconstruction of abdominal wall defects of any size by general surgeons.

PMID- 24566433
TI  - Night owl women are similar to men in their relationship orientation, risk-taking
      propensities, and cortisol levels: Implications for the adaptive significance and
      evolution of eveningness.
AB  - Individual differences in morningness/eveningness are relatively stable over time
      and, in part, genetically based. The night-owl pattern is more prevalent in men
      than in women, particularly after puberty and before women reach menopause. It
      has been suggested that eveningness evolved relatively recently in human
      evolutionary history and that this trait may be advantageous to individuals
      pursuing short-term mating strategies. Consistent with this hypothesis,
      eveningness is associated with extraversion, novelty-seeking, and in males, with
      a higher number of sexual partners. In this study, I investigated whether
      eveningness is associated with short-term relationship orientation, higher risk
      taking, and higher testosterone or cortisol. Both female and male night-owls were
      more likely to be single than in long-term relationships than early morning
      individuals. Eveningness was associated with higher risk-taking in women but not
      in men; this association was not testosterone-dependent but mediated by cortisol.
      Female night-owls had average cortisol profiles and risk-taking tendencies more
      similar to those of males than to those of early-morning females. Taken together,
      these findings provide some support to the hypothesis that eveningness is
      associated with psychological and behavioral traits that are instrumental in
      short-term mating strategies, with the evidence being stronger for women than for
      men.

PMID- 24566434
TI  - A high-dose Shiitake mushroom increases hepatic accumulation of triacylglycerol
      in rats fed a high-fat diet: underlying mechanism.
AB  - Shiitake mushroom have been shown to have health benefits including lowering
      plasma lipids and preventing body weight gain. However, their underlying
      mechanisms are largely unknown. The study aim was to assess the potential
      underlying mechanism of Shiitake mushrooms in lowering plasma triacylglycerol
      (TAG) in rats fed a high fat diet (HFD). Forty Wistar rats were divided into
      control group were given HFD and treatment group were fed HFD, enriched with
      Shiitake mushroom powder at a low dose (LD-M): 0.7%, medium dose (MD-M): 2%, or
      high dose (HD-M): 6% (wt:wt) for six weeks. Diets were isocaloric containing ~50%
      energy from fat. After six weeks' dietary intervention, the rats were sacrificed,
      and blood and tissue samples were collected. The HD-M group showed a
      significantly higher ratio of liver weight to 100 g body weight (p < 0.05), a
      more severe hepatic steatosis marker, such as hepatocyte ballooning (p < 0.0001),
      and more liver triacylglycerol content than LD-M and MD-M (p < 0.05). HD-M also
      showed a significantly decreased ratio of phosphatidylcholine (PC) to
      phosphatidylethanolamine (PE) compared to HFD (p < 0.05), however, there were no
      differences compared to HD-M and MD-M. Our results also showed a positive
      association between the dosage, liver TAG, and liver ballooning histology. A
      negative association was found between the mushroom dosage and the ratio of liver
      PC to PE. This study showed the mechanism of how high-dose Shiitake mushroom (HD
      M) prevents obesity by increasing TAG accumulation in the liver, rather than
      adipose tissue. 

PMID- 24566436
TI  - Characterization of oilseed lipids from "DHA-producing Camelina sativa": a new
      transformed land plant containing long-chain omega-3 oils.
AB  - New and sustainable sources of long-chain (LC, >=C20) omega-3 oils containing DHA
      (docosahexaenoic acid, 22:6omega3) are required to meet increasing demands. The
      lipid content of the oilseed of a novel transgenic, DHA-producing land plant,
      Camelina sativa, containing microalgal genes able to produce LC omega-3 oils,
      contained 36% lipid by weight with triacylglycerols (TAG) as the major lipid
      class in hexane extracts (96% of total lipid). Subsequent chloroform-methanol
      (CM) extraction recovered further lipid (~50% polar lipid, comprising glycolipids
      and phospholipids) and residual TAG. The main phospholipid species were
      phosphatidyl choline and phosphatidyl ethanolamine. The % DHA was: 6.8% (of total
      fatty acids) in the TAG-rich hexane extract and 4.2% in the polar lipid-rich CM
      extract. The relative level of ALA (alpha-linolenic acid, 18:3omega3) in DHA
      camelina seed was higher than the control. Major sterols in both DHA- and control
      camelina seeds were: sitosterol, campesterol, cholesterol, brassicasterol and
      isofucosterol. C16-C22 fatty alcohols, including iso-branched and odd-chain
      alcohols were present, including high levels of iso-17:0, 17:0 and 19:0. Other
      alcohols present were: 16:0, iso-18:0, 18:0 and 18:1 and the proportions varied
      between the hexane and CM extracts. These iso-branched odd-chain fatty alcohols,
      to our knowledge, have not been previously reported. These components may be
      derived from wax esters, or free fatty alcohols.

PMID- 24566437
TI  - Nutrients utilization in obese individuals with and without hypertriglyceridemia.
AB  - BACKGROUND: Low fat utilization is linked to weight gain and to the presence of
      certain atherosclerosis markers. It is not clear whether the presence of
      hyperlipidemia can further affect nutrients utilization. The main objective of
      this study was to investigate the fasting fuel utilization of obese subjects
      suffering from hypertriglyceridemia, and to compare it with that of individuals
      that are solely obese. METHOD: We recruited 20 obese individuals with
      hypertriglyceridemia and 20 matched individuals not affected by
      hypertriglyceridemia. The fuel utilization (respiratory quotient) was measured by
      respiratory gas exchange, by Indirect Calorimetry. RESULTS: There was a
      significant difference in fuel utilization and HDL-cholesterol between cases and
      controls (respiratory quotient 0.89 +/- 0.07 vs. 0.84 +/- 0.06; p = 0.020
      respectively). The univariate and multivariate linear regression analysis
      confirmed that hypertrygliceridemia was positively correlated to the respiratory
      quotient (p = 0.035). CONCLUSION: obese subjects with hypertriglyceridemia had a
      higher respiratory quotient in comparison to unaffected subjects. This could
      suggest a limitation in the beta-oxidation mechanisms; this could actually imply
      that fatty acids may be redirected from oxidation to reesterification into
      triglycerides. The study could suggest the presence of different mechanisms
      unrelated to obesity and also a potential new therapeutic target for
      hypertriglyceridemia management.

PMID- 24566435
TI  - Vitamin D deficiency in India: prevalence, causalities and interventions.
AB  - Vitamin D deficiency prevails in epidemic proportions all over the Indian
      subcontinent, with a prevalence of 70%-100% in the general population. In India,
      widely consumed food items such as dairy products are rarely fortified with
      vitamin D. Indian socioreligious and cultural practices do not facilitate
      adequate sun exposure, thereby negating potential benefits of plentiful sunshine.
      Consequently, subclinical vitamin D deficiency is highly prevalent in both urban
      and rural settings, and across all socioeconomic and geographic strata. Vitamin D
      deficiency is likely to play an important role in the very high prevalence of
      rickets, osteoporosis, cardiovascular diseases, diabetes, cancer and infections
      such as tuberculosis in India. Fortification of staple foods with vitamin D is
      the most viable population based strategy to achieve vitamin D sufficiency.
      Unfortunately, even in advanced countries like USA and Canada, food fortification
      strategies with vitamin D have been only partially effective and have largely
      failed to attain vitamin D sufficiency. This article reviews the status of
      vitamin D nutrition in the Indian subcontinent and also the underlying causes for
      this epidemic. Implementation of population based educational and interventional
      strategies to combat this scourge require recognition of vitamin D deficiency as
      a public health problem by the governing bodies so that healthcare funds can be
      allocated appropriately. 

PMID- 24566439
TI  - Prevalence of dietary supplement use in healthy pre-school Chinese children in
      Australia and China.
AB  - There is a growing use of dietary supplements in many countries including China.
      This study aimed to document the prevalence of dietary supplements use and
      characteristics of Chinese pre-school children using dietary supplements in
      Australia and China. A survey was carried out in Perth, Western Australia of 237
      mothers with children under five years old and 2079 in Chengdu and Wuhan, China.
      A total of 22.6% and 32.4% of the Chinese children were taking dietary
      supplements in Australia and China, respectively. In China, the most commonly
      used dietary supplements were calcium (58.5%) and zinc (40.4%), while in
      Australia, the most frequently used types were multi-vitamins/minerals (46.2%)
      and fish oil (42.3%). In Australia, "not working", "never breastfeed", "higher
      education level of the mother" and "older age of the child" were associated with
      dietary supplement use in children. In China, being unwell and "having higher
      household income" were significantly related to dietary supplement usage. Because
      of the unknown effects of many supplements on growth and development and the
      potential for adverse drug interactions, parents should exercise caution when
      giving their infants or young children dietary supplements. Wherever possible it
      is preferable to achieve nutrient intakes from a varied diet rather than from
      supplements. 

PMID- 24566438
TI  - Omega-3 index and cardiovascular health.
AB  - Recent large trials with eicosapentaenoic acid (EPA) and docosahexaenoic acid
      (DHA) in the cardiovascular field did not demonstrate a beneficial effect in
      terms of reductions of clinical endpoints like total mortality, sudden cardiac
      arrest or other major adverse cardiac events. Pertinent guidelines do not
      uniformly recommend EPA + DHA for cardiac patients. In contrast, in epidemiologic
      findings, higher blood levels of EPA + DHA were consistently associated with a
      lower risk for the endpoints mentioned. Because of low biological and analytical
      variability, a standardized analytical procedure, a large database and for other
      reasons, blood levels of EPA + DHA are frequently assessed in erythrocytes, using
      the HS-Omega-3 Index(r) methodology. A low Omega-3 Index fulfills the current
      criteria for a novel cardiovascular risk factor. Neutral results of intervention
      trials can be explained by issues of bioavailability and trial design that
      surfaced after the trials were initiated. In the future, incorporating the Omega
      3 Index into trial designs by recruiting participants with a low Omega-3 Index
      and treating them within a pre-specified target range (e.g., 8%-11%), will make
      more efficient trials possible and provide clearer answers to the questions asked
      than previously possible. 

PMID- 24566440
TI  - Montmorency cherries reduce the oxidative stress and inflammatory responses to
      repeated days high-intensity stochastic cycling.
AB  - This investigation examined the impact of Montmorency tart cherry concentrate
      (MC) on physiological indices of oxidative stress, inflammation and muscle damage
      across 3 days simulated road cycle racing. Trained cyclists (n = 16) were divided
      into equal groups and consumed 30 mL of MC or placebo (PLA), twice per day for
      seven consecutive days. A simulated, high-intensity, stochastic road cycling
      trial, lasting 109 min, was completed on days 5, 6 and 7. Oxidative stress and
      inflammation were measured from blood samples collected at baseline and
      immediately pre- and post-trial on days 5, 6 and 7. Analyses for lipid
      hydroperoxides (LOOH), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF
      alpha), interleukin-8 (IL-8), interleukin-1-beta (IL-1-beta), high-sensitivity C
      reactive protein (hsCRP) and creatine kinase (CK) were conducted. LOOH (p <
      0.01), IL-6 (p < 0.05) and hsCRP (p < 0.05) responses to trials were lower in the
      MC group versus PLA. No group or interaction effects were found for the other
      markers. The attenuated oxidative and inflammatory responses suggest MC may be
      efficacious in combating post-exercise oxidative and inflammatory cascades that
      can contribute to cellular disruption. Additionally, we demonstrate direct
      application for MC in repeated days cycling and conceivably other sporting
      scenario's where back-to-back performances are required. 

PMID- 24566442
TI  - Estimated levels of gluten incidentally present in a Canadian gluten-free diet.
AB  - Avoiding exposure to gluten is currently the only effective treatment for celiac
      disease. However, the evidence suggests that for most affected individuals,
      exposure to less than 10 mg/day is unlikely to cause histological changes to the
      intestinal mucosa. The daily diet of people with celiac disease does not rely
      solely on gluten-free pre-packaged foods, but also on naturally gluten-free
      grains (e.g., rice, buckwheat, ...) and foods with grain-derived ingredients
      (i.e., flour and starches) used for cooking and baking at home. The objective of
      this study was to estimate the level of incidental gluten potentially present in
      gluten-free diets from a Canadian perspective. We have conducted gluten exposure
      estimations from grain-containing foods and foods with grain-derived ingredients,
      taking into consideration the various rates of food consumption by different sex
      and age groups. These estimates have concluded that if gluten was present at
      levels not exceeding 20 ppm, exposure to gluten would remain below 10 mg per day
      for all age groups studied. However, in reality the level of gluten found in
      naturally gluten-free ingredients is not static and there may be some concerns
      related to the flours made from naturally gluten-free cereal grains. It was found
      that those containing a higher level of fiber and that are frequently used to
      prepare daily foods by individuals with celiac disease could be a concern. For
      this category of products, only the flours and starches labelled "gluten-free"
      should be used for home-made preparations. 

PMID- 24566443
TI  - Meat consumption as a risk factor for type 2 diabetes.
AB  - Disease risk factors identified in epidemiological studies serve as important
      public health tools, helping clinicians identify individuals who may benefit from
      more aggressive screening or risk-modification procedures, allowing policymakers
      to prioritize intervention programs, and encouraging at-risk individuals to
      modify behavior and improve their health. These factors have been based primarily
      on evidence from cross-sectional and prospective studies, as most do not lend
      themselves to randomized trials. While some risk factors are not modifiable,
      eating habits are subject to change through both individual action and broader
      policy initiatives. Meat consumption has been frequently investigated as a
      variable associated with diabetes risk, but it has not yet been described as a
      diabetes risk factor. In this article, we evaluate the evidence supporting the
      use of meat consumption as a clinically useful risk factor for type 2 diabetes,
      based on studies evaluating the risks associated with meat consumption as a
      categorical dietary characteristic (i.e., meat consumption versus no meat
      consumption), as a scalar variable (i.e., gradations of meat consumption), or as
      part of a broader dietary pattern. 

PMID- 24566444
TI  - Supplement timing of cranberry extract plays a key role in promoting
      Caenorhabditis elegans healthspan.
AB  - Consumption of nutraceuticals is a major and potent dietary intervention for
      delaying aging. As the timing of administration is critical for the efficacy of
      bioactive compounds in medicine, the effectiveness of nutraceuticals may also be
      dramatically affected by the timing of supplementation. Cranberry exact (CBE),
      rich in polyphenols, is consumed as a nutraceutical, and possesses anti-aging
      properties. Here, we examined the influence of timing on the beneficial effects
      of CBE supplementation in C. elegans. The prolongevity effect of CBE in different
      aged worms, young adults, middle-age adults, and aged adults, was determined.
      Early-start intervention with CBE prolonged the remaining lifespan of worms of
      different ages more robustly than late-start intervention. The effectiveness of
      CBE on stress responses and physiological behaviors in different aged worms was
      also investigated. The early-start intervention prominently promoted motility and
      resistance to heat shocks and V. cholera infection, especially in aged worms.
      Together, these findings suggest that the timing of CBE supplementation
      critically influences its beneficial effects on C. elegans lifespan and
      healthspan. It is of interest to further investigate whether the similar results
      would occur in humans. 

PMID- 24566445
TI  - Specialty bias in treatment recommendations and quality of life among radiation
      oncologists and urologists for localized prostate cancer.
AB  - BACKGROUND: Given the importance of physician attitudes about different
      treatments and the quality of life (QOL) in prostate cancer, we performed a
      national survey of specialists to assess treatment recommendations and
      perceptions of treatment-related survival and QOL. METHODS: We mailed a self
      administered survey instrument to a random sample of 1366 specialists in the U.S.
      Respondents were asked for treatment recommendations and survival that varied by
      PSA levels and Gleason scores and estimate QOL outcomes. Pearson's chi-square and
      multivariable regression models were used to test for differences in each
      outcome. RESULTS: Response rates were similar for radiation oncologists (52.6%)
      and urologists (52.3%; P=0.92). Across all risk strata, urologists were more
      likely to recommend surgery than were radiation oncologists, for conditions
      ranging from PSA>20 and Gleason score 8-10 (35.2 vs. 0.2%; P<0.001) to PSA 4-10
      and Gleason score 7 (87.5 vs. 20.9%; P<0.001). Radiation oncologists were also
      more likely to recommend radiation therapy relative to urologists (all P<0.001).
      From low- to high-risk prostate cancer, radiation oncologists and urologists
      perceived their treatment as being better for improving survival (all P<0.001).
      Each specialty also viewed their treatment as having less urinary incontinence
      (all P<0.001). CONCLUSIONS: Radiation oncologists and urologists both prefer the
      treatment modalities they offer, perceive them to be more effective and to lead
      to a better QOL. Patients may be receiving biased information, and a truly
      informed consent process with shared decision-making may be possible only if they
      are evaluated by both specialties before deciding upon a treatment course.

PMID- 24566446
TI  - Chemical toxicity and radiological health detriment associated with the
      inhalation of various enrichments of uranium.
AB  - The occupational risks associated with the chemical toxicity of uranium can be
      overlooked during the processing, handling and storage of the material, as the
      radioactivity of the material is often used alone to assess the health
      consequences of exposure to uranium compounds. This note provides a summary of
      the current United Kingdom occupational standards for uranium based on radiation
      dose and/or chemical toxicity with a particular focus on intake via inhalation. A
      simple model is subsequently presented to allow a comparison to be drawn between
      the occupational exposure standard for chemical toxicity and radiological dose
      limit. Using these data a set of suggested limits on occupational exposure to
      airborne uranium is proposed that indicate where the legal annual radiological
      dose limit for workers or the Health and Safety Executive occupational exposure
      standard for chemical toxicity are at risk of being breached. 

PMID- 24566441
TI  - Cocoa polyphenols and inflammatory markers of cardiovascular disease.
AB  - Epidemiological studies have demonstrated the beneficial effect of plant-derived
      food intake in reducing the risk of cardiovascular disease (CVD). The potential
      bioactivity of cocoa and its polyphenolic components in modulating cardiovascular
      health is now being studied worldwide and continues to grow at a rapid pace. In
      fact, the high polyphenol content of cocoa is of particular interest from the
      nutritional and pharmacological viewpoints. Cocoa polyphenols are shown to
      possess a range of cardiovascular-protective properties, and can play a
      meaningful role through modulating different inflammatory markers involved in
      atherosclerosis. Accumulated evidence on related anti-inflammatory effects of
      cocoa polyphenols is summarized in the present review. 

PMID- 24566448
TI  - What should a case-finding tool for dysphagia in long term care residents with
      dementia look like?

PMID- 24566447
TI  - Delirium superimposed on dementia strongly predicts worse outcomes in older
      rehabilitation inpatients.
AB  - OBJECTIVE: Delirium superimposed on dementia (DSD) is common in many settings.
      Nonetheless, little is known about the association between DSD and clinical
      outcomes. The study aim was to evaluate the association between DSD and related
      adverse outcomes at discharge from rehabilitation and at 1-year follow-up in
      older inpatients undergoing rehabilitation. DESIGN: Prospective cohort study.
      SETTING: Hospital rehabilitation unit. PARTICIPANTS: A total of 2642 patients
      aged 65 years or older admitted between January 2002 and December 2006.
      MEASUREMENTS: Dementia predating rehabilitation admission was detected by DSM-III
      R criteria. Delirium was diagnosed with the DSM-IV-TR. The primary outcome was
      that of walking dependence (Barthel Index mobility subitem score of <15) captured
      as a trajectory from discharge to 1-year follow-up. A mixed-effects multivariate
      logistic regression model was used to analyze the association between DSD and
      outcome, after adjusting for relevant covariates. Secondary outcomes were
      institutionalization and mortality at 1-year follow-up, and logistic regression
      models were used to analyze these associations. RESULTS: The median age was 77
      years (interquartile range: 71-83). The prevalence of DSD was 8%, and the
      prevalence of delirium and dementia alone were 4% and 22%, respectively. DSD at
      admission was found to be significantly associated with almost a 15-fold increase
      in the odds of walking dependence (odds ratio [OR] 15.5; 95% Confidence Interval
      [CI] 5.6-42.7; P < .01). DSD was also significantly associated with a fivefold
      increase in the risk of institutionalization (OR 5.0; 95% CI 2.8-8.9; P < .01)
      and an almost twofold increase in the risk of mortality (OR 1.8; 95% CI 1.1-2.8;
      P = .01). CONCLUSIONS: DSD is a strong predictor of functional dependence,
      institutionalization, and mortality in older patients admitted to a
      rehabilitation setting, suggesting that strategies to detect DSD routinely in
      practice should be developed and DSD should be included in prognostic models of
      health care.

PMID- 24566451
TI  - The dynamic surface tension of atmospheric aerosol surfactants reveals new
      aspects of cloud activation.
AB  - The activation of aerosol particles into cloud droplets in the Earth's atmosphere
      is both a key process for the climate budget and a main source of uncertainty.
      Its investigation is facing major experimental challenges, as no technique can
      measure the main driving parameters, the Raoult's term and surface tension,
      sigma, for sub-micron atmospheric particles. In addition, the surfactant fraction
      of atmospheric aerosols could not be isolated until recently. Here we present the
      first dynamic investigation of the total surfactant fraction of atmospheric
      aerosols, evidencing adsorption barriers that limit their gradient (partitioning)
      in particles and should enhance their cloud-forming efficiency compared with
      current models. The results also show that the equilibration time of surfactants
      in sub-micron atmospheric particles should be beyond the detection of most on
      line instruments. Such instrumental and theoretical shortcomings would be
      consistent with atmospheric and laboratory observations and could have limited
      the understanding of cloud activation until now. 

PMID- 24566449
TI  - Exploring the role of muscle mass, obesity, and age in the relationship between
      muscle quality and physical function.
AB  - BACKGROUND: Divergent conclusions emerge from the literature regarding the
      relationship between muscle quality (defined as muscle strength per unit of
      muscle mass) and physical function. These contrasted results may be due to the
      influence of factors such as age, obesity, and muscle mass itself. Consequently,
      the aim of the present study was to explore the role of these factors in the
      relationship between muscle quality (MQ) and physical function. METHODS: Data are
      from 312 individuals (97 men and 215 women) aged 50 years and older. Body
      composition (dual energy X-ray absorptiometry) and knee extension strength of the
      right leg (1 repetition maximum) were assessed. Appendicular lean body mass index
      (AppLBMI) and MQ (knee extension strength /right leg lean mass) were calculated.
      A composite score of physical function was created based on the timed up-and-go,
      alternate step, sit-to-stand, and balance tests. RESULTS: MQ was significantly
      associated with physical function when AppLBMI (beta = 0.179; P = .004) and body
      mass index (BMI) (beta = 0.178; P = .003), but not age (beta = 0.065; P = .26),
      were included in regression analysis. AppLBMI (beta = 0.221; P < .001), BMI (beta
      = 0.234; P < .001), and age (beta = 0.134; P = .018) significantly interacted
      with MQ to determine physical function. CONCLUSIONS: Our results show that muscle
      mass, obesity, and age influence the relationship between MQ and physical
      function, suggesting that these factors should be taken into account when
      interpreting MQ. Even so, higher levels of MQ were associated with higher
      physical function scores. Nutritional and physical activity interventions may be
      designed in this regard.

PMID- 24566453
TI  - Editorial. This journal has evolved over many decades.

PMID- 24566454
TI  - Commentary on Lee et al. Osteophyte excision without cyst excision for a mucous
      cyst of the finger.

PMID- 24566452
TI  - The implication of frailty on preoperative risk assessment.
AB  - PURPOSE OF REVIEW: Frailty, a state of decreased homeostatic reserve, is
      characterized by dysregulation across multiple physiologic and molecular
      pathways. It is particularly relevant to the perioperative period, during which
      patients are subject to high levels of stress and inflammation. This review aims
      to familiarize the anesthesiologist with the most current concepts regarding
      frailty and its emerging role in preoperative assessment and risk stratification.
      RECENT FINDINGS: Current literature has established frailty as a significant
      predictor of operative complications, institutionalization, and death among
      elderly surgical patients. A variety of scoring systems have been proposed to
      preoperatively identify and assess frail patients, though they differ in their
      clinical utility and prognostic ability. Additionally, evidence suggests an
      evolving potential for preoperative intervention and modification of the frailty
      syndrome. SUMMARY: The elderly are medically complex and heterogeneous with
      respect to operative risk. Recent advances in the concept of frailty provide an
      evidence-based framework to guide the anesthesiologist in the perioperative
      management, evaluation, and risk stratification of older surgical patients.

PMID- 24566455
TI  - Re: del Pinal F. Editorial: I have a dream ... reflex sympathetic dystrophy (RSD
      or Complex Regional Pain Syndrome - CRPS I) does not exist. J Hand Surg Eur.
      2013, 38: 595-7.

PMID- 24566457
TI  - Notice of dual publication.

PMID- 24566456
TI  - Harold E. Kleinert MD October 7, 1921-September 28, 2013.

PMID- 24566460
TI  - The role of besifloxacin in the treatment of bacterial conjunctivitis.
AB  - OBJECTIVE: To evaluate the role of besifloxacin in bacterial conjunctivitis
      treatment. DATA SOURCES: Searches were made on MEDLINE/PubMed and EMBASE (January
      2007 to January 2014) using the terms besifloxacin and Besivance. References from
      these publications were reviewed for additional resources. Additional information
      was collected from Bausch & Lomb, the manufacturer of Besivance;
      www.clinicaltrials.gov; and American Academy of Ophthalmology. STUDY SELECTION
      AND DATA EXTRACTION: English-language documents were reviewed for pharmacology,
      pharmacokinetics, efficacy, and safety, with priority on clinical trials. DATA
      SYNTHESIS: Three large randomized controlled clinical trials established the
      safety and efficacy of besifloxacin ophthalmic suspension 0.6% compared with
      placebo or active comparator (moxifloxacin ophthalmic solution 0.5%) given 3
      times a day for 5 days for acute bacterial conjunctivitis (BC) treatment.
      Compared with placebo, besifloxacin had clinically superior bacterial eradication
      rates and was noninferior to moxifloxacin. Besifloxacin was compared with placebo
      in 2 randomized, placebo-controlled trials, dosed twice a day for 3 days.
      Superior efficacy was seen compared with placebo, which supports the shorter
      dosing schedule. Ophthalmic besifloxacin is well tolerated; the most common
      adverse effect (conjunctival redness) occurred in 2% of patients. Adverse effects
      in 1% to 2% of patients included blurred vision, eye pain, eye irritation, eye
      pruritus, and headache. CONCLUSION: Besifloxacin 0.6% ophthalmic suspension 3
      times a day for 5 days is safe and effective for BC. Twice-a-day dosing for 3
      days was also effective-a simplified regimen compared with other
      fluoroquinolones. Disadvantages include price and lack of a generic. Further
      evaluation is needed to evaluate comparative efficacy among other ocular
      fluoroquinolones and unlabeled uses.

PMID- 24566461
TI  - Topiramate for migraine prophylaxis in pediatric patients.
AB  - OBJECTIVE: To evaluate the currently published data pertaining to the efficacy
      and safety of topiramate for prophylaxis of classic and common migraine in
      pediatric patients. DATA SOURCES: The literature was identified via PubMed
      (through April 2013) and Iowa Drug Information System (through April 2013).
      References from identified articles were also reviewed. STUDY SELECTION AND DATA
      EXTRACTION: Data were included from studies of efficacy and safety in pediatric
      patients experiencing migraine (with or without aura), as defined by the
      International Headache Society. Studies including patients with more specific
      types of migraine, such as basilar migraine, were excluded. DATA SYNTHESIS: Eight
      publicatons were identified, including 3 randomized controlled trials (RCTs), a
      subgroup analysis, and 4 observational studies. These studies reported a decrease
      in headache frequency ranging from 63% to 100% for doses of 100 mg/d and 65% for
      200 mg/d. Response to therapy, defined as >=50% reduction in migraine rate, was
      also reported in 83% to 95% of patients receiving topiramate. Topiramate is
      generally well tolerated. Adverse effects were dose related and included
      paresthesias, weight loss, and cognitive adverse effects. CONCLUSION: Topiramate
      is an effective and well-tolerated prophylactic therapy for use in pediatric
      migraine patients. Doses of 100 and 200 mg/d (1.47-2.0 mg/kg/d) effectively
      decrease the frequency of migraine headaches, with 100 mg/d providing optimal
      benefit-to-risk ratio. Additional randomized, double-blind, placebo-controlled
      studies are needed to determine the impact of the drug on quality-of-life
      outcomes, such as school function, and migraine severity and duration.

PMID- 24566463
TI  - Role of calcitonin gene-related peptide in cardioprotection of short-term and
      long-term exercise preconditioning.
AB  - PURPOSE: To examine the role of calcitonin gene-related peptide (CGRP) in
      cardioprotection of short-term and long-term exercise preconditioning (EP).
      METHODS: Male Sprague-Dawley rats were, respectively, subjected to continuous
      intermittent treadmill training 3 days or 3 weeks as short-term or long-term EP
      protocols. The myocardial injury induced by isoproterenol (ISO) was performed 24
      hours after short-term and long-term EP. The myocardial injury was evaluated in
      terms of the serum cardiac troponin levels and the hematoxylin-basic fuchsin
      picric acid staining. Additionally, serum CGRP levels, CGRP expression in the
      dorsal root ganglion (DRG), and heart were analyzed as possible mechanisms to
      explain short-term and long-term EP-induced cardioprotection. RESULTS: Both short
      term and long-term EP markedly attenuated the isoproterenol-induced myocardial
      ischemia with lower serum cardiac troponin levels. Short-term EP does not alter
      serum CGRP levels and CGRP expression in the DRG and heart. Long-term EP
      significantly increases serum CGRP levels and CGRP expression in the DRG and
      heart. CONCLUSIONS: The results indicate that short-term EP does not increase the
      synthesis and release of CGRP. Therefore, the cardioprotective effect of short
      term EP does not involve CGRP adaptation. Furthermore, long-term EP increases
      CGRP synthesis in the DRG and promotes CGRP release in the blood and heart.
      Hence, CGRP may play an important role in the cardioprotective effect of long
      term EP.

PMID- 24566464
TI  - Optimal duration of dual antiplatelet therapy after drug-eluting stent
      implantation: a meta-analysis of 3 randomized controlled trials.
AB  - PURPOSE: The optimal duration of dual antiplatelet therapy (DAPT) after drug
      eluting stent (DES) implantation is still unclear. We conducted a meta-analysis
      of randomized trials to assess the optimal duration of DAPT after DES
      implantation. METHODS: Articles were identified through a literature search of
      EMBASE, Pubmed, Europubmed, and the Cochrane Library until November 2013. Data
      were independently extracted by 2 reviewers. A random effect model was used to
      calculate the pooled odds ratios (ORs) with 95% confidence intervals (CIs) of the
      clinical outcomes concerned. RESULTS: Three randomized controlled trials with
      zotarolimus- or everolimus-eluting stents and 6679 patients were included. There
      were no significant differences between short-term DAPT and standard-term DAPT in
      the comparison of incidences of cardiac death (OR, 0.84; 95% CI, 0.53-1.35; P =
      0.48), myocardial infarction (OR, 1.21; 95% CI, 0.83-1.75; P = 0.32), stent
      thrombosis (OR, 1.30; 95% CI, 0.50-3.39; P = 0.59), and target vessel
      revascularization (OR, 1.16; 95% CI, 0.89-1.52; P = 0.26). Short-term DAPT did
      not increase the risk of all-cause death (OR, 0.86; 95% CI, 0.59-1.26; P = 0.44),
      cerebrovascular accidents (OR, 0.88; 95% CI, 0.421.81; P = 0.72), and major
      bleeding events (OR, 0.59; 95% CI, 0.30-1.15; P = 0.12). CONCLUSIONS: The results
      indicate that short-term DAPT do not increase the risk of cardiac death,
      myocardial infarction, stent thrombosis, target vessel revascularization, major
      bleeding, cerebrovascular accidents, and all-cause death at 12 months after
      implantation of DES compared with current standard-term DAPT. However, only 3
      studies with second generation of DES are included in this meta-analysis. Further
      well-designed studies are still needed.

PMID- 24566462
TI  - PP2 prevents beta-adrenergic stimulation of cardiac pacemaker activity.
AB  - One of the main strategies for cancer therapy is to use tyrosine kinase
      inhibitors for inhibiting tumor proliferation. Increasing evidence has
      demonstrated the potential risks of cardiac arrhythmias (such as prolonged QT
      interval) of these drugs. We report here that a widely used selective inhibitor
      of Src tyrosine kinases, 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4
      d]pyrimidine (PP2), can inhibit and prevent beta-adrenergic stimulation of
      cardiac pacemaker activity. First, in dissected rat sinus node, PP2 inhibited and
      prevented the isoproterenol-induced increase of spontaneous beating rate. Second,
      in isolated rat sinus node myocytes, PP2 suppressed the hyperpolarization
      activated "funny" current (traditionally called cardiac pacemaker current, I(f))
      by negatively shifting the activation curve and decelerating activation kinetics.
      Third, in isolated rat sinus node myocytes, PP2 decreased the Src kinase
      activity, the cell surface expression, and tyrosine phosphorylation of
      hyperpolarization-activated, cyclic nucleotide-modulated channel 4 (HCN4) channel
      proteins. Finally, in human embryonic kidney 293 cells overexpressing recombinant
      human HCN4 channels, PP2 reversed the enhancement of HCN4 channels by
      isoproterenol and inhibited 573x, a cyclic adenosine momophosphate-insensitive
      human HCN4 mutant. These results demonstrated that inhibition of Src kinase
      activity in heart by PP2 decreased and prevented beta-adrenergic stimulation of
      cardiac pacemaker activity. These effects are mediated, at least partially, by a
      cAMP-independent attenuation of channel activity and cell surface expression of
      HCN4, the main channel protein that controls the heart rate.

PMID- 24566465
TI  - Predictive value of intrahepatic hepatitis B virus covalently closed circular DNA
      and total DNA in patients with acute hepatitis B and patients with chronic
      hepatitis B receiving anti-viral treatment.
AB  - This study aimed to investigate the persistence and predictive values of
      intrahepatic (IH) hepatitis B virus (HBV) covalently closed circular DNA (cccDNA)
      and total DNA (tDNA) in patients with acute hepatitis B (AHB) and patients with
      chronic hepatitis B (CHB) receiving anti-viral treatment. The levels of IH cccDNA
      and tDNA, serum HBV DNA, hepatitis B surface antigen (HBsAg), hepatitis B e
      antigen (HBeAg) and alanine aminotransferase (ALT) were detected in 11 patients
      with AHB and 46 patients with CHB who were receiving anti-viral treatment, among
      whom 21 had primary treatment failure, 11 achieved virological response (VR) and
      15 achieved VR and HBsAg seroclearance. The median IH cccDNA and tDNA levels in
      the patients with AHB (0.002 copies/cell and 0.04 copies/cell, respectively) were
      significantly lower than those in the patients with CHB. In the patients with
      CHB, the median IH cccDNA level among individuals who achieved VR and HBsAg
      seroclearance (0.012 copies/cell) was significantly lower than that in those who
      had failed primary treatment (4.18 copies/cell, P<0.0001) but not that in those
      who achieved solely VR (0.039 copies/cell, P=0.169). The median IH tDNA level in
      patients with CHB who achevied VR and HBsAg seroclearance (0.096 copies/cell) was
      significantly lower than that in those who failed primary treatment (371
      copies/cell, P<0.0001) and those who achieved solely VR (1.62 copies/cell,
      P=0.001). No significant difference was observed in the area under the receiver
      operating characteristic (ROC) curve, which was used to predict the likelihood of
      achieving VR and HBsAg seroclearance, between IH tDNA and IH cccDNA levels (0.96
      and 0.88, respectively; P>0.10). IH cccDNA levels were shown to be positively
      correlated with serum ALT (P=0.024), HBeAg (P=0.001) and IH tDNA levels
      (P<0.0001), but not with serum HBV DNA (P=0.12) and HBsAg levels in either HBeAg
      positive (P=0.84) or in HBeAg-negative (P=0.146) patients. In conclusion, IH
      cccDNA may persist in patients with AHB and patients with CHB who acheive VR and
      HBsAg seroclearance following anti-viral treatment. Furthermore, IH cccDNA and
      tDNA may have potential in predicting successful therapeutic response in patients
      with CHB who receive anti-viral treatment.

PMID- 24566467
TI  - Phase II multicenter study of docetaxel and bevacizumab with or without
      trastuzumab as first-line treatment for patients with metastatic breast cancer.
AB  - BACKGROUND: Adding bevacizumab to docetaxel or paclitaxel in the first-line
      improves the progression-free survival (PFS) of metastatic breast cancer (MBC)
      patients. Docetaxel has been studied with bevacizumab at the maximally tolerated
      dose of 100 mg/m(2). We investigated the effects of combining bevacizumab with
      docetaxel (75 mg/m(2)) with or without trastuzumab for human epidermal growth
      factor receptor 2-positive (HER2(+)) and HER2-negative (HER2(-)) patients,
      respectively. PATIENTS AND METHODS: We conducted a phase II study, stratified by
      HER2 status, of patients with locally advanced breast cancer or MBC who had
      received no prior chemotherapy for metastatic disease and showed no evidence or
      history of central nervous system metastases. Stratum 1 (HER2(-)) treatment
      consisted of bevacizumab (15 mg/kg) followed by docetaxel (75 mg/m(2))
      administered every 3 weeks; stratum 2 (HER2(+)) treatment was the same as that of
      stratum 1 with the addition of trastuzumab (8 mg/kg loading dose on day 2 of
      cycle 1, and 6 mg/kg on day 1 of all subsequent cycles). RESULTS: The trial
      accrued 73 patients (stratum 1, 52 patients; stratum 2, 21 patients). The most
      common grade 3 or 4 adverse event (all strata) was fatigue (stratum 1, 11.5%;
      stratum 2, 10%). The incidence of grade 3 hypertension was 6% for stratum 1 and
      5% for stratum 2. The median PFS was 8.4 months (95% CI, 5.2-10.4 months) in
      stratum 1; the median PFS in stratum 2 was 13.3 months (95% CI, 11.9-35.4
      months). The overall response rate for stratum 1was 58% and for stratum 2 was
      81%, and the clinical benefit rates were 67% and 81%, respectively. CONCLUSION:
      In first-line treatment of MBC, adding docetaxel (75 mg/m(2)) to bevacizumab
      administered every 3 weeks in HER2(-) patients, and docetaxel plus trastuzumab
      plus bevacizumab treatment in HER2(+) patients are feasible and safe, with high
      response rates and promising PFS compared with those of bevacizumab-naive
      historic controls.

PMID- 24566469
TI  - Inhibition of myeloperoxidase- and neutrophil-mediated oxidant production by
      tetraethyl and tetramethyl nitroxides.
AB  - The powerful oxidant HOCl (hypochlorous acid and its corresponding anion, (-)OCl)
      generated by the myeloperoxidase (MPO)-H2O2-Cl(-) system of activated leukocytes
      is strongly associated with multiple human inflammatory diseases; consequently
      there is considerable interest in inhibition of this enzyme. Nitroxides are
      established antioxidants of low toxicity that can attenuate oxidation in animal
      models, with this ascribed to superoxide dismutase or radical-scavenging
      activities. We have shown (M.D. Rees et al., Biochem. J. 421, 79-86, 2009) that
      nitroxides, including 4-amino-TEMPO (4-amino-2,2,6,6-tetramethylpiperidin-1
      yloxyl radical), are potent inhibitors of HOCl formation by isolated MPO and
      activated neutrophils, with IC50 values of ~1 and ~6 uM respectively. The utility
      of tetramethyl-substituted nitroxides is, however, limited by their rapid
      reduction by biological reductants. The corresponding tetraethyl-substituted
      nitroxides have, however, been reported to be less susceptible to reduction. In
      this study we show that the tetraethyl species were reduced less rapidly than the
      tetramethyl species by both human plasma (89-99% decreased rate of reduction) and
      activated human neutrophils (62-75% decreased rate). The tetraethyl-substituted
      nitroxides retained their ability to inhibit HOCl production by MPO and activated
      neutrophils with IC50 values in the low-micromolar range; in some cases
      inhibition was enhanced compared to tetramethyl substitution. Nitroxides with
      rigid structures (fused oxaspiro rings) were, however, inactive. Overall, these
      data indicate that tetraethyl-substituted nitroxides are potent inhibitors of
      oxidant formation by MPO, with longer plasma and cellular half-lives compared to
      the tetramethyl species, potentially allowing lower doses to be employed.

PMID- 24566468
TI  - Cytotoxic effects of 15d-PGJ2 against osteosarcoma through ROS-mediated AKT and
      cell cycle inhibition.
AB  - Polo-like kinase 1 (PLK1), a critical cell cycle regulator, has been identified
      as a potential target in osteosarcoma (OS). 15-deoxy-Delta12, 14-prostaglandin J2
      (15d-PGJ2), a prostaglandin derivative, has shown its anti-tumor activity by
      inducing apoptosis through reactive oxygen species (ROS)-mediated inactivation of
      v-akt, a murine thymoma viral oncogene homolog, (AKT) in cancer cells. In the
      study analyzing its effects on arthritis, 15d-PGJ2 mediated shear-induced
      chondrocyte apoptosis via protein kinase A (PKA)-dependent regulation of PLK1. In
      this study, the cytotoxic effect and mechanism underlying 15d-PGJ2 effects
      against OS were explored using OS cell lines. 15d-PGJ2 induced significant G2/M
      arrest, and exerted time- and dose-dependent cytotoxic effects against all OS
      cell lines. Western blot analysis showed that both AKT and PKA-PLK1 were down
      regulated in OS cell lines after treatment with 15d-PGJ2. In addition,
      transfection of constitutively active AKT or PLK1 partially rescued cells from
      15d-PGJ2-induced apoptosis, suggesting crucial roles for both pathways in the
      anti-cancer effects of 15d-PGJ2. Moreover, ROS generation was found treatment
      with 15d-PGJ2, and its cytotoxic effect could be reversed with N-acetyl-l
      cysteine. Furthermore, inhibition of JNK partially rescued 15d-PGJ2 cytotoxicity.
      Thus, ROS-mediated JNK activation may contribute to apoptosis through down
      regulation of the p-Akt and PKA-PLK1 pathways. 15d-PGJ2 is a potential
      therapeutic agent for OS, exerting cytotoxicity mediated through both AKT and PKA
      PLK1 inhibition, and these results form the basis for further analysis of its
      role in animal studies and clinical applications. 

PMID- 24566470
TI  - GPx8 peroxidase prevents leakage of H2O2 from the endoplasmic reticulum.
AB  - Unbalanced endoplasmic reticulum (ER) homeostasis (ER stress) leads to increased
      generation of reactive oxygen species (ROS). Disulfide-bond formation in the ER
      by Ero1 family oxidases produces hydrogen peroxide (H2O2) and thereby constitutes
      one potential source of ER-stress-induced ROS. However, we demonstrate that
      Ero1alpha-derived H2O2 is rapidly cleared by glutathione peroxidase (GPx) 8. In
      293 cells, GPx8 and reduced/activated forms of Ero1alpha co-reside in the rough
      ER subdomain. Loss of GPx8 causes ER stress, leakage of Ero1alpha-derived H2O2 to
      the cytosol, and cell death. In contrast, peroxiredoxin (Prx) IV, another H2O2
      detoxifying rough ER enzyme, does not protect from Ero1alpha-mediated toxicity,
      as is currently proposed. Only when Ero1alpha-catalyzed H2O2 production is
      artificially maximized can PrxIV participate in its reduction. We conclude that
      the peroxidase activity of the described Ero1alpha-GPx8 complex prevents
      diffusion of Ero1alpha-derived H2O2 within and out of the rough ER. Along with
      the induction of GPX8 in ER-stressed cells, these findings question a ubiquitous
      role of Ero1alpha as a producer of cytoplasmic ROS under ER stress. 

PMID- 24566471
TI  - Expression and interaction of small heat shock proteins (sHsps) in rice in
      response to heat stress.
AB  - The inherent immobility of rice (Oryza sativa L.) limited their abilities to
      avoid heat stress and required them to contend with heat stress through innate
      defense abilities in which heat shock proteins played important roles. In this
      study, Hsp26.7, Hsp23.2, Hsp17.9A, Hsp17.4 and Hsp16.9A were up-regulated in
      Nipponbare during seedling and anthesis stages in response to heat stress.
      Subsequently, the expressing levels of these five sHsps in the heat-tolerant rice
      cultivar, Co39, were all significantly higher than that in the heat-susceptible
      rice cultivar, Azucena. This indicated that the expressive level of these five
      sHsps was positively related to the ability of rice plants to avoid heat stress.
      Thus, the expression level of these five sHsps can be regarded as bio-markers for
      screening rice cultivars with different abilities to avoid heat stress. Hsp18.1,
      Hsp17.9A, Hsp17.7 and Hsp16.9A, in the three rice cultivars under heat stress
      were found to be involved in one protein complex by Native-PAGE, and the
      interactions of Hsp18.1 and Hsp 17.7, Hsp18.1 and Hsp 17.9A, and Hsp17.7 and
      Hsp16.9A were further validated by yeast 2-hybridization. Pull down assay also
      confirmed the interaction between Hsp17.7 and Hsp16.9A in rice under heat stress.
      In conclusion, the up-regulation of the 5 sHsps is a key step for rice to
      tolerate heat stress, after that some sHsps assembled into a large hetero
      oligomeric complex. In addition, through protein-protein interaction, Hsp101
      regulated thiamine biosynthesis, and Hsp82 homology affected nitrogen metabolism,
      while Hsp81-1 were involved in the maintenance of sugar or starch synthesis in
      rice plants under heat stress. These results provide new insight into the
      regulatory mechanism of sHsps in rice. 

PMID- 24566472
TI  - Biochemical characterisation of glyceraldehyde 3-phosphate dehydrogenase (GAPDH)
      from the liver fluke, Fasciola hepatica.
AB  - Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) catalyses one of the two steps
      in glycolysis which generate the reduced coenzyme NADH. This reaction precedes
      the two ATP generating steps. Thus, inhibition of GAPDH will lead to
      substantially reduced energy generation. Consequently, there has been
      considerable interest in developing GAPDH inhibitors as anti-cancer and anti
      parasitic agents. Here, we describe the biochemical characterisation of GAPDH
      from the common liver fluke Fasciola hepatica (FhGAPDH). The primary sequence of
      FhGAPDH is similar to that from other trematodes and the predicted structure
      shows high similarity to those from other animals including the mammalian hosts.
      FhGAPDH lacks a binding pocket which has been exploited in the design of novel
      antitrypanosomal compounds. The protein can be expressed in, and purified from
      Escherichia coli; the recombinant protein was active and showed no cooperativity
      towards glyceraldehyde 3-phosphate as a substrate. In the absence of ligands,
      FhGAPDH was a mixture of homodimers and tetramers, as judged by protein-protein
      crosslinking and analytical gel filtration. The addition of either NAD+ or
      glyceraldehyde 3-phosphate shifted this equilibrium towards a compact dimer.
      Thermal scanning fluorimetry demonstrated that this form was considerably more
      stable than the unliganded one. These responses to ligand binding differ from
      those seen in mammalian enzymes. These differences could be exploited in the
      discovery of reagents which selectively disrupt the function of FhGAPDH.

PMID- 24566473
TI  - A mechanical nanogate based on a carbon nanotube for reversible control of ion
      conduction.
AB  - Control of mass transport through nanochannels is of critical importance in many
      nanoscale devices and nanofiltration membranes. The gates in biological channels,
      which control the transport of substances across cell membranes, can provide
      inspiration for this purpose. Gates in many biological channels are formed by a
      constriction ringed with hydrophobic residues which can prevent ion conduction
      even when they are not completely physically occluded. In this work, we use
      molecular dynamics simulations to design a nanogate inspired by this hydrophobic
      gating mechanism. Deforming a carbon nanotube (12,12) with an external force can
      form a hydrophobic constriction in the centre of the tube that controls ion
      conduction. The simulation results show that increasing the magnitude of the
      applied force narrows the constriction and lowers the fluxes of K(+) and Cl(-)
      found under an electric field. With the exerted force larger than 5 nN, the
      constriction blocks the conduction of K(+) and Cl(-) due to partial dehydration
      while allowing for a noticeable water flux. Ion conduction can revert back to the
      unperturbed level upon force retraction, suggesting the reversibility of the
      nanogate. The force can be exerted by available experimental facilities, such as
      atomic force microscope (AFM) tips. It is found that partial dehydration in a
      continuous water-filled hydrophobic constriction is enough to close the channel,
      while full dewetting is not necessarily required. This mechanically deformed
      nanogate has many potential applications, such as a valve in nanofluidic systems
      to reversibly control ion conduction and a high-performance nanomachine for
      desalination and water treatment. 

PMID- 24566475
TI  - An analysis of a large dataset on immigrant integration in Spain. The statistical
      mechanics perspective on social action.
AB  - How does immigrant integration in a country change with immigration density?
      Guided by a statistical mechanics perspective we propose a novel approach to this
      problem. The analysis focuses on classical integration quantifiers such as the
      percentage of jobs (temporary and permanent) given to immigrants, mixed
      marriages, and newborns with parents of mixed origin. We find that the average
      values of different quantifiers may exhibit either linear or non-linear growth on
      immigrant density and we suggest that social action, a concept identified by Max
      Weber, causes the observed non-linearity. Using the statistical mechanics notion
      of interaction to quantitatively emulate social action, a unified mathematical
      model for integration is proposed and it is shown to explain both growth
      behaviors observed. The linear theory instead, ignoring the possibility of
      interaction effects would underestimate the quantifiers up to 30% when immigrant
      densities are low, and overestimate them as much when densities are high. The
      capacity to quantitatively isolate different types of integration mechanisms
      makes our framework a suitable tool in the quest for more efficient integration
      policies. 

PMID- 24566474
TI  - Vitamin, mineral, and multivitamin supplements for the primary prevention of
      cardiovascular disease and cancer: U.S. Preventive services Task Force
      recommendation statement.
AB  - DESCRIPTION: Update of the 2003 U.S. Preventive Services Task Force (USPSTF)
      recommendation on vitamin supplementation to prevent cardiovascular disease and
      cancer. METHODS: The USPSTF reviewed the evidence on the efficacy of multivitamin
      or mineral supplements in the general adult population for the prevention of
      cardiovascular disease and cancer. POPULATION: This recommendation applies to
      healthy adults without special nutritional needs (typically aged 50 years or
      older). It does not apply to children, women who are pregnant or may become
      pregnant, or persons who are chronically ill or hospitalized or have a known
      nutritional deficiency. RECOMMENDATION: The USPSTF concludes that the current
      evidence is insufficient to assess the balance of benefits and harms of
      multivitamins for the prevention of cardiovascular disease or cancer. (I
      statement). The USPSTF concludes that the current evidence is insufficient to
      assess the balance of benefits and harms of single- or paired-nutrient
      supplements (except beta-carotene and vitamin E) for the prevention of
      cardiovascular disease or cancer. (I statement). The USPSTF recommends against
      beta-carotene or vitamin E supplements for the prevention of cardiovascular
      disease or cancer. (D recommendation).

PMID- 24566476
TI  - A case of symptomatic mass in the right iliac fossa: a Bermuda Triangle which
      often lies the right diagnosis.
AB  - Disease of the iliac fossa can often be accompanied by non-specific symptoms and
      some of these are exclusively caused by the compression of bulky masses of other
      neighboring structures. In young women a differential diagnosis is a non trivial
      task as several possible causes have to be taken into account. Thus,
      intraligamentary tumors, which are extremely rare finding, are frequently
      confused with uterus, ovary or intestinal tumors. Even if myomas are the most
      benign tumors of the female genital tract, broad ligament leiomyomas are an
      unusual finding in women of reproductive age. These tumors are often asymptomatic
      until they reach a volume likely to cause symptoms related to the mass pressure.
      An accurate patient's anamnesis and examination serve as a guide to further
      examinations. Ultrasound is the first line imaging as it can show ovarian or
      other pelvic mass and doesn't involve exposure to radiations in young patients,
      who can be pregnant. We describe the clinical presentation and imaging features
      of a broad ligament leiomyoma, which presented as an inguinal mass in a patient
      with a right iliac fossa pain. We also report our diagnostic process performing
      the differential diagnosis with other potential pathologies of RIF. In these
      cases, a preoperative disease classification discriminating the benign or
      malignant tumor nature is closely linked to the proper patient management.

PMID- 24566477
TI  - The impact of the pre-procedural hemodynamic assessment in transcatheter aortic
      valve replacement.

PMID- 24566478
TI  - Successful use of a cryoablation sheath for closure of problematic atrial septal
      defect.

PMID- 24566479
TI  - Cardiac arrest and ventricular tachycardia from coronary embolism: an unusual
      presentation of infective endocarditis.

PMID- 24566480
TI  - A rare cause of congestive heart failure after seven years of open heart surgery:
      Organized intrapericardial hematoma.

PMID- 24566481
TI  - A case of radial arteriovenous fistula during coronary angiography.

PMID- 24566482
TI  - An invitation for rethinking about gamma-glutamyltransferase and its association
      with coronary collaterals.

PMID- 24566483
TI  - Right ventricular functions in obstructive nasal polyposis.

PMID- 24566484
TI  - Does bilirubin level have an effect on cardiac parameters?

PMID- 24566485
TI  - Real-time three dimensional transesophageal echocardiography has an incremental
      value in delineation of paravalvular leakages.

PMID- 24566486
TI  - Industry compliant health care provider: accepting defeat.

PMID- 24566487
TI  - Can white blood cell count be used as a predictor of atrial fibrillation
      following cardiac surgery? A short literature review.

PMID- 24566488
TI  - Optical coherence tomography imaging of intrastent neointimal bridge caused by
      semicircumferencial dissection after drug eluting balloon dilatation of instent
      restenosis of sapheneous venous graft.

PMID- 24566489
TI  - Aortic saddle embolism caused by right ventricle thrombus in a 2-year-old girl
      with Ebstein anomaly and Glenn shunt.

PMID- 24566490
TI  - Change in electrocardiography after cardiopulmoner resuscitation.

PMID- 24566492
TI  - Urogynecology digest : presented by Omar F. Duenas-Garcia.

PMID- 24566493
TI  - Vulvar anatomy and labia minoraplasty.
AB  - AIM OF VIDEO/INTRODUCTION: Female genital cosmetic surgery is performed for
      aesthetic reasons as well as for medical and functional indications, such as
      congenital labia minora hypertrophy. The purpose of this video is to teach vulvar
      anatomy and review labia minorplasty techniques. METHODS: We demonstrate one
      technique in this video. CONCLUSIONS: There are a variety of different techniques
      for labia minorplasty. When deciding the most appropriate technique to use, the
      patient's goals must be considered.

PMID- 24566494
TI  - Mesh retraction correlates with vaginal pain and overactive bladder symptoms
      after anterior vaginal mesh repair: reply to comment by Jacquetin.

PMID- 24566495
TI  - Mesh retraction correlates with vaginal pain and overactive bladder symptoms
      after anterior vaginal mesh repair: comment on Rogowski et al.

PMID- 24566496
TI  - NF-Y inactivation causes atypical neurodegeneration characterized by ubiquitin
      and p62 accumulation and endoplasmic reticulum disorganization.
AB  - Nuclear transcription factor-Y (NF-Y), a key regulator of cell-cycle progression,
      often loses its activity during differentiation into nonproliferative cells. In
      contrast, NF-Y is still active in mature, differentiated neurons, although its
      neuronal significance remains obscure. Here we show that conditional deletion of
      the subunit NF-YA in postmitotic mouse neurons induces progressive
      neurodegeneration with distinctive ubiquitin/p62 pathology; these proteins are
      not incorporated into filamentous inclusion but co-accumulated with insoluble
      membrane proteins broadly on endoplasmic reticulum (ER). The degeneration also
      accompanies drastic ER disorganization, that is, an aberrant increase in ribosome
      free ER in the perinuclear region, without inducing ER stress response. We
      further perform chromatin immunoprecipitation and identify several NF-Y
      physiological targets including Grp94 potentially involved in ER disorganization.
      We propose that NF-Y is involved in a unique regulation mechanism of ER
      organization in mature neurons and its disruption causes previously undescribed
      novel neuropathology accompanying abnormal ubiquitin/p62 accumulation. 

PMID- 24566498
TI  - Epirubicin directly promotes hepatitis B virus (HBV) replication in stable HBV
      expressing cell lines: a novel mechanism of HBV reactivation following anticancer
      chemotherapy.
AB  - Chronic hepatitis B virus (HBV) infection is a worldwide problem and HBV
      reactivation following anticancer chemotherapy has become an emerging clinical
      challenge. However, the mechanisms of HBV reactivation following chemotherapy
      remain unclear. Epirubicin is an anthracycline drug used in chemotherapy to treat
      numerous types of malignancy, including breast cancer, acute leukemia, malignant
      lymphoma, lung cancer, ovarian cancer and stomach cancer. Epirubicin acts by
      intercalating DNA strands and inhibiting DNA and RNA synthesis. In this study, it
      was demonstrated that epirubicin directly upregulated the levels of in vitro HBV
      replication in a concentration-dependent manner. Exposure to epirubicin for 24 h
      induced >11- and 6-fold increases in the levels of intracellular and secreted HBV
      DNA, respectively. In concordance with the elevated levels of HBV DNA, the
      expression levels of HBV pregenomic RNA, intracellular HBV surface and HBV core
      antigens, and secreted HBV e antigen were significantly increased by treatment
      with 0.5 uM epirubicin. Notably, epirubicin promoted cellular excretion of HBV
      nucleocapsids, which are closely associated with the pathological effects of HBV,
      including acute liver failure. In conclusion, epirubicin exhibited a direct
      stimulatory effect on HBV replication and this may be a novel mechanism of HBV
      reactivation following cytotoxic anticancer chemotherapy.

PMID- 24566499
TI  - Diagnosis and Treatment of Venous Malformations. Consensus Document of the
      International Union of Phlebology (IUP): updated 2013.
AB  - Venous malformations (VMs) are the most common vascular developmental anomalies
      (birth defects) . These defects are caused by developmental arrest of the venous
      system during various stages of embryogenesis. VMs remain a difficult diagnostic
      and therapeutic challenge due to the wide range of clinical presentations,
      unpredictable clinical course, erratic response to the treatment with high
      recurrence/ persistence rates, high morbidity following non-specific conventional
      treatment, and confusing terminology. The Consensus Panel reviewed the recent
      scientific literature up to the year 2013 to update a previous IUP Consensus
      (2009) on the same subject. ISSVA Classification with special merits for the
      differentiation between the congenital vascular malformation (CVM) and vascular
      tumors was reinforced with an additional review on syndrome-based classification.
      A "modified" Hamburg classification was adopted to emphasize the importance of
      extratruncular vs. truncular sub-types of VMs. This incorporated the
      embryological ongm, morphological differences, unique characteristics, prognosis
      and recurrence rates of VMs based on this embryological classification. The
      definition and classification of VMs were strengthened with the addition of
      angiographic data that determines the hemodynamic characteristics, the anatomical
      pattern of draining veins and hence the risk of complication following
      sclerotherapy. The hemolymphatic malformations, a combined condition
      incorporating LMs and other CVMs, were illustrated as a separate topic to
      differentiate from isolated VMs and to rectify the existing confusion with name
      based eponyms such as Klippei-Trenaunay syndrome. Contemporary concepts on VMs
      were updated with new data including genetic findings linked to the etiology of
      CVMs and chronic cerebrospinal venous insufficiency. Besides, newly established
      information on coagulopathy including the role of D-Dimer was thoroughly reviewed
      to provide guidelines on investigations and anticoagulation therapy in the
      management of VMs. Congenital vascular bone syndrome resulting in angio-osteo
      hyper/hypotrophy and (lateral) marginal vein was separately reviewed. Background
      data on arterio-venous malformations was included to differentiate this anomaly
      from syndromebased VMs. For the treatment, a new section on laser therapy and
      also a practical guideline for follow up assessment were added to strengthen the
      management principle of the multidisciplinary approach. All other therapeutic
      modalities were thoroughly updated to accommodate a changing concept through the
      years.

PMID- 24566500
TI  - Quality of live as measured by the CIVQ 20. Questionnaire following oral
      mesoglycan treatment of patients with chronic venous disease.
AB  - AIM: Several studies have demonstrated the effective antithrombotic action of
      mesoglycan to treat chronic venous disease (CVD). The study aimed to assess
      clinical and quality of life (QoL) (CIVIQ 20 questionnaire) improvements in
      mesoglycan-treated patients with clinical, etiological, anatomical and
      pathophysiological (CEAP) stages 2 and 3. METHODS: The open, multicentre,
      uncontrolled, observational, prospective study involved treating patients with 50
      mg x 2/day mesoglycan for 2 months and measuring improvement to lower-limb edema
      and QoL in the Global, Physical, Pain, Psychological, and Social Dimensions of
      the Chronic Venous Disease Quality-of-Life Questionnaire (CIVIQ 20) at the first,
      baseline visit (V1), at the end of treatment (V2) and 2 (V3) and 4 months after
      treatment completion (V4). At the last visit (V4), patient disease status was
      assessed objectively (by the treating physician) and subjectively (by the
      patient). The study population was divided into three groups: 1) patients with
      only varicose veins; 2) patients with only lower-limb edema; 3) patients with
      varicose veins and edema (ITT population). RESULTS: Seventy-five centers enrolled
      1066 patients (ITT population); 914 patients completed the study. Mesoglycan
      treatment produced significant improvement of edema and lower-limb circumference
      at every visit, in both patients with edema alone and those with edema and
      varicose veins (paired sample t-test P<0.001). QoL improved significantly in all
      questionnaire dimensions in all three patient groups even after treatment was
      concluded (V2). Improvement continued up to the end of the study observation
      period (V4) (paired sample t-test P<0.001). Objective clinical improvement of the
      underlying CVD was found in 76.82% of patients with varicose veins alone, in
      82.83% of patients with edema alone, and in 76.7% of patients with varicose veins
      and edema. Patients' own subjective assessment of improvement was 82.0%, 79.39%
      and 79.39% respectively for the three groups. CONCLUSION: Results showed
      mesoglycan treatment to improve QoL significantly in patients with CVD as
      measured by a specific questionnaire like the CIVIQ 20. The extent of average
      edema reduction observed at the last visit (4 months after the end of drug
      treatment), suggests mesoglycan might have an etiological role, modifying the
      physiological factors underlying CVD and not just affording temporary improvement
      of symptoms.

PMID- 24566502
TI  - Psychiatry on trial: the Norway 2011 massacre.
AB  - On July 22, 2011, Anders Breivik, a Norwegian citizen, detonated a fertilizer
      bomb near government buildings in Oslo, killing eight people, and then proceeded
      to a nearby island where the Labor Party was holding a youth camp. There, he
      killed 69 people before being arrested. Just before these events, he posted a
      "compendium" on the Web explaining his actions and encouraging others to do
      likewise. Much of the ensuing media coverage and trial focused on whether he was
      sane and whether he had a psychiatric diagnosis. One team of court-appointed
      psychiatrists found him to be psychotic with a diagnosis of paranoid
      schizophrenia and legally insane. A second team found him neither psychotic nor
      schizophrenic and, thus, legally sane. Their contrary opinions were not
      reconciled by observing his behavior in court. We discuss why experienced
      psychiatrists reached such fundamentally opposing diagnostic conclusions about a
      "home-grown" terrorist holding extreme political views. 

PMID- 24566501
TI  - Digestive enzymes of two brachyuran and two anomuran land crabs from Christmas
      Island, Indian Ocean.
AB  - The digestive ability of four sympatric land crabs species (the gecarcinids,
      Gecarcoidea natalis and Discoplax celeste and the anomurans, Birgus latro and
      Coenobita perlatus) was examined by determining the activity of their digestive
      enzymes. The gecarcinids are detritivores that consume mainly leaf litter; the
      robber crab, B. latro, is an omnivore that preferentially consumes items high in
      lipid, carbohydrate and/or protein; C. perlatus is also an omnivore/detritivore.
      All species possess protease, lipase and amylase activity for hydrolysing
      ubiquitous protein, lipid and storage polysaccharides (glycogen and starch).
      Similarly all species possess enzymes such as N-acetyl-beta-D-glucosaminidase,
      the cellulases, endo-beta-1,4-glucanase and beta-glucohydrolase and
      hemicellulases, lichenase and laminarinase for the respective hydrolysis of
      structural substrates chitin, cellulose and hemicelluloses, lichenan and
      laminarin. Except for the enzyme activities of C. perlatus, enzyme activity could
      not be correlated to dietary preference. Perhaps others factors such as olfactory
      and locomotor ability and metabolic status may determine the observed dietary
      preferences. The digestive fluid of C. perlatus possessed higher endo-beta-1,4
      glucanase, lichenase and laminarinase activities compared to that of the other
      species. Thus, C. perlatus may be efficient at digestion of cellulose and
      hemicellulose within plant material. Zymography indicated that the majority of
      protease, lipase, phosphatase, amylase, endo-beta-1,4-glucanase, beta
      glucohydrolase and N-acetyl-beta-D-glucosaminidase isozymes were common to all
      species, and hence were inherited from a common aquatic ancestor. Differences
      were observed for the phosphatase, lipase and endo-beta-1,4-glucanase isozymes.
      These differences are discussed in relation to phylogeny and possible evolution
      to cope with the adoption of a terrestrial diet. 

PMID- 24566503
TI  - The therapeutic relationship after psychiatric admission.
AB  - The therapeutic relationship is one of the most central and important factors in
      the treatment of mental health disorders. A better therapeutic relationship is
      associated with service engagement, medication adherence, and satisfaction with
      services. This study aimed to compare the demographic and clinical factors
      associated with the therapeutic relationship in voluntarily and involuntarily
      admitted psychiatric service users. We found that individuals who had been
      admitted involuntarily, who had a diagnosis of a psychotic disorder, and who
      reported higher levels of perceived pressures on admission were more likely to
      have a poorer therapeutic relationship with their consultant psychiatrist.
      Greater levels of insight and treatment satisfaction, together with higher levels
      of procedural justice experienced on admission, were associated with a better
      therapeutic relationship. We found that the level of perceived coercion on
      admission was not related to the therapeutic relationship. Targeted interventions
      to improve the therapeutic relationship, particularly for involuntarily admitted
      service users, are discussed. 

PMID- 24566504
TI  - Psychiatric symptoms moderate the effects of mental illness self-management in a
      randomized controlled trial.
AB  - Depression has been shown to moderate the effects of physical illness self
      management (ISM) programs. We attempted to replicate these findings for a mental
      ISM intervention. Outpatients with serious mental illness (N = 428) from eight
      Tennessee communities were randomly assigned to receive a peer-led self
      management intervention called Building Recovery of Individual Dreams and Goals
      Through Education and Support or services as usual. Psychiatric symptoms were
      assessed with the Brief Symptom Inventory; the outcome of personal empowerment
      was measured by the Empowerment Scale. Intent-to-treat analysis using mixed
      effects random regression found significant interaction effects between study
      condition and three moderating symptom profiles. Empowerment was greater for the
      intervention participants with high levels of depressive symptoms, anxiety
      symptoms, and general symptom distress than for the experimental participants
      with low symptom levels and the control subjects with high or low levels of
      symptoms. These results shed light on how mental ISM programs operate and ways
      these can be improved. 

PMID- 24566505
TI  - Labor migration and mental health in Cambodia: a qualitative study.
AB  - Labor migration is thought to have significant mental and physical health
      impacts, given the risks for exploitation and abuse of migrant workers,
      particularly among those in semiskilled and unskilled positions, although
      empirical data are limited. This qualitative study, conducted in July 2010 in
      Banteay Meanchey Province, Cambodia, focused on psychosocial and mental health
      signs and symptoms associated with labor migration among Cambodian migrant
      workers to Thailand. Two qualitative methods identified a number of mental health
      problems faced by Cambodian migrant workers in Thailand, including the presence
      of anxiety and depression-like problems among this population, described in local
      terminology as pibak chet (sadness), keut chreun (thinking too much), and khval
      khvay khnong chet (worry in heart). Key informants revealed the extent to which
      psychosocial well-being is associated with conditions of poverty, including debt
      and lack of access to basic services. 

PMID- 24566506
TI  - Congolese and Somali beliefs about mental health services.
AB  - Despite high levels of traumatic exposure, refugees often do not seek mental
      health services upon resettlement. The purpose of this study was to examine both
      concepts of mental illness in addition to attitudes and beliefs about treatment
      as well as potential barriers to accessing mental health services. To that end,
      qualitative research was done using focus groups with Congolese and Somali men
      and women in the United States (n = 48) in addition to a community survey with
      women from those communities (n = 296) administered by staff of a community-based
      organization. Mental health concerns, although identified, were often dealt with
      first in the communities themselves with the help of family or friends. Great
      emphasis was placed on their respective communities of faith. The actual role of
      mental health professionals was not well understood, and there was apparent
      hesitancy to use services, which also relates to issues of stigma. 

PMID- 24566507
TI  - Social cognition and levels of personality organization in patients with
      somatoform disorders: a case-control study.
AB  - Social cognition and its association with level of personality organization (PO)
      were examined in 163 patients with severe somatoform disorders (SFDs) and 151
      psychiatric (PSA) control patients. Social cognition was measured with the Social
      Cognition and Object Relations Scale, which assessed both affective and cognitive
      facets of social cognition. Levels of PO were assessed using theory-driven
      profiles of the Dutch Short Form of the Minnesota Multiphasic Personality
      Inventory (MMPI). The SFD patients exhibited impairments in the cognitive facets
      of social cognition but not more so than the PSA controls. The results for the
      affective aspects indicated that the SFD patients exhibited lower levels of
      emotional investment yet higher affect tone in interactions than the PSA
      controls. In contrast to the control group, level of PO was not associated with
      social cognition in SFD. Together, the results indicated that impairments in
      complexity of mental representations are not specific to SFD patients, yet
      impairments in emotional investment may be specific to SFD. 

PMID- 24566508
TI  - Discrimination and social anxiety disorder among African-Americans, Caribbean
      blacks, and non-Hispanic whites.
AB  - The present study investigated the relationship between discrimination and social
      anxiety disorder (SAD) in a sample of African-Americans, Caribbean blacks, and
      non-Hispanic whites using the National Survey of American Life, the most
      comprehensive study of psychopathology among American blacks to date (N = 6082).
      Previous work has highlighted a strong association between discrimination and
      mental health symptoms (Keith, Lincoln, Taylor, and Jackson [Sex Roles 62:48-59,
      ]; Kessler, Mickelson, and Williams [J Health Soc Behav 40:208-230, 1999]; Soto,
      Dawson-Andoh, and BeLue [J Anxiety Disord 25:258-265, ]). However, few studies
      have examined the effects of particular types of discrimination on specific
      anxiety disorders or among different black subgroups. In this study, logistic
      regression analyses indicated that everyday but not major experiences of
      discrimination are associated with SAD for African-Americans, Caribbean blacks,
      and non-Hispanic whites. This study adds to the extant literature by
      demonstrating that specific types of discrimination may be uniquely associated
      with SAD for different ethnic/racial groups. 

PMID- 24566509
TI  - Health service and medication use among veterans with persistent postconcussive
      symptoms.
AB  - Persistent postconcussive symptoms (PPCS) are noted when a series of cognitive,
      emotional, and somatosensory complaints persist for months after a concussion.
      Clinical management of PPCS can be challenging in the veteran population because
      of the nonspecific nature of symptoms and co-occurrence with affective
      disturbances such as posttraumatic stress disorder (PTSD) and chronic pain. In
      this study, we compared health service and medication use patterns in a sample of
      421 veterans with PPCS with an age-matched cohort of case controls. The results
      suggest that the veterans with PPCS showed high rates of medical and mental
      health service utilization during a mean treatment period of 2 years. Although
      chronic pain commonly co-occurs with PPCS in veterans, service use and medication
      prescribing trends seem to have been influenced more by the presence of PTSD than
      chronic pain. Our findings reinforce the overlap among PPCS, PTSD, and chronic
      pain and demonstrate the complexity inherent in treating these conditions in
      veterans. 

PMID- 24566511
TI  - Risk taking in adolescents with attention deficit hyperactivity disorder on a
      probabilistic choice task.
AB  - Risk taking is commonly attributed to individuals with attention deficit
      hyperactivity disorder (ADHD). This study investigated whether adolescents with
      ADHD would choose to take greater risks on a probabilistic task in which
      contingencies are explicitly presented. Adolescents with and without ADHD, aged
      13 to 18 years, performed a modified version of the Cambridge Gambling Task. The
      subjects with ADHD risked smaller sums and chose the unfavorable outcomes more
      frequently than did the controls but had the same speed of decision and risk
      adjustment. The results indicate that their poor decisions were not due to
      impulsivity or insensitivity to the concept of probability and that increased
      risk taking is not always associated with ADHD. Moreover, in situations that do
      not demand learning of contingencies, ADHD may be associated with decreased,
      rather than increased, risk taking. 

PMID- 24566510
TI  - Mental health service use among trauma-exposed adults: a mixed-methods study.
AB  - Research findings indicate that many urban trauma-exposed individuals do not
      access needed mental health care; therefore, it is critical to identify factors
      associated with the use of mental health services for this group. This study used
      a mixed-methods approach to examine predictors of mental health service use and
      barriers to care. Quantitative findings showed that significantly more adults who
      were male and black with a lower education and income did not report current
      mental health service use. After controlling for covariates, individuals with
      lower trauma exposure (odds ratio [OR], 0.7; 95% confidence interval [CI], 0.5
      0.9) and higher depression symptom scores (OR, 1.0; 95% CI, 1.0-1.1) were
      significantly more likely to report current mental health service use.
      Qualitative findings indicated that fear, low mental health literacy,
      helplessness, and psychosocial issues were identified as barriers to mental
      health treatment. Implications for treatment and future research are discussed. 

PMID- 24566512
TI  - Cognitive subdomain responses to galantamine in Alzheimer's disease.
AB  - We investigated the effects of galantamine on cognitive subdomains in Alzheimer's
      disease (AD). Sixty-six patients with mild-to-moderate AD received open-label
      galantamine for 52 weeks. Cognitive function was measured using the Korean
      version of the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog
      K). Response to galantamine was defined as "improvement or no deterioration" on
      the total scores of the ADAS-cog-K at 26 weeks. In the overall intent-to-treat
      sample, we found less cognitive decline during 26 and 52 weeks than the expected
      untreated course as predicted by Stern's equation. The operationally defined
      response rate at 26 weeks was 66.7%. The responders differed significantly from
      the nonresponders only in the memory and language domains but not in the domains
      of praxis or frontal/executive function or in secondary outcome measures of
      neuropsychiatric symptoms and activities of daily living. The subdomain analysis
      revealed an effect of galantamine on preservation of memory that was not apparent
      in the overall analysis. Failure to achieve responder status by 26 weeks was
      associated with no further possibility of response. 

PMID- 24566513
TI  - Heart failure: a complex clinical process interpreted by systems biology approach
      and network medicine.
AB  - Systems biology is founded on the principles of integrative computational
      analysis and on the data from genetic and molecular components. The integration
      of biological components produces interacting networks, modules and phenotypes
      with remarkable applications in the field of clinical medicine. The evolving
      concept of network medicine gives a more precise picture of the intrinsic
      complexity of failing myocardium and its clinical consequences. The present
      review is focused on the impact of network cardiology in explaining the
      progressive nature of the clinical syndrome of heart failure. The failing
      myocardium and the subsequent clinical syndrome of heart failure disclose a
      dynamical and non-linear system with a progressive picture of clinical
      deterioration. The classical description of heart failure is based on tissue
      pathology and clinical presentation, and lately on specific genetic and molecular
      modifications. This characterization of heart failure has significant limitations
      to recognize preclinical disease features and to explain the progressive nature
      of the syndrome. Systems biology detects and evaluates specific networks from
      molecular, cellular and tissue elements, and assesses their influence on the
      appearance of clinical phenotypes. The classical reductive concept of heart
      failure is inadequate to provide data for molecular dysfunctions or defective
      coordination of the interconnected network components that are central to the
      genesis and clinical deterioration of heart failure. In heart failure, the
      recognition of molecular targets within the complex networks will increase the
      conceptual basis of pharmacology and the identification of novel biomarkers and
      at the same time will accelerate the discovery of new drugs. 

PMID- 24566514
TI  - Renal denervation.
AB  - Severe hypertension, resistant to conventional antihypertensive medications, is
      associated with major adverse cardiovascular and cerebrovascular events and renal
      insufficiency. Renal sympathetic nerve over-activity frequently accompanies
      essential hypertension. Catheter-based renal sympathetic denervation leads to a
      reduction in renal and overall sympathetic nerve activity and improvement in
      blood pressure in the setting of severe resistant hypertension. In the following,
      we review the role of the renal sympathetic nervous system in blood pressure
      control and recent clinical experience with renal denervation. Furthermore,
      potential beneficial effects on diabetes control, obstructive sleep apnea, atrial
      and ventricular arrhythmias are discussed. 

PMID- 24566515
TI  - Approach to cases with resistant hypertension.
AB  - Resistant hypertension is defined as blood pressure that remains above 140/90 mm
      Hg despite the concurrent use of optimal dose of 3 antihypertensive agents of
      different classes. Ideally, 1 of these 3 agents should be a diuretic agent. The
      etiology of resistance hypertension is multifactorial. Successful treatment
      requires identification and reversal of lifestyle factors (obesity, dietary salt
      intake, alcohol intake, lack of adherence to prescribed medicines, and
      interfering substances), and to exclude the presence of pseudoresistance. Once
      confounding factors have been ruled out, evaluation for potentially treatable
      secondary causes of hypertension should be considered. Most forms of secondary
      hypertension are related with adrenal or renal disorders such as primary
      hyperaldosteronism and renovascular disease. Although, obstructive sleep apnea
      syndrome is not a typical cause of secondary hypertension, it is commonly present
      in resistant hypertension. Diagnostic workup and management of resistant
      hypertension were discussed in different clinical presentations. 

PMID- 24566516
TI  - Evaluation of pulmonary vascular resistance and vasoreactivity testing with
      oxygen in children with congenital heart disease and pulmonary arterial
      hypertension.

PMID- 24566517
TI  - IL-10R1 (Ser138Gly) functional polymorphism is associated with acute myocardial
      infarction in Tunisian patients.

PMID- 24566518
TI  - Almanac 2013: acute coronary syndromes.
AB  - Unstable coronary artery plaque is the most common underlying cause of acute
      coronary syndromes (ACS) and can manifest as unstable angina, non-ST segment
      elevation infarction (NSTE-ACS), and ST elevation myocardial infarction (STEMI),
      but can also manifest as sudden cardiac arrest due to ischaemia induced
      tachyarrhythmias. ACS mortality has decreased significantly over the last few
      years, especially from the more extreme manifestations of ACS, STEMI, and cardiac
      arrest. This trend is likely to continue based on recent therapeutic progress
      which includes novel antiplatelet agents such as prasugrel, ticagrelor, and
      cangrelor.

PMID- 24566519
TI  - Antenatal acetaminophen use and attention-deficit/hyperactivity disorder: an
      interesting observed association but too early to infer causality.

PMID- 24566520
TI  - Phosphatases and kinases as regulators of the endothelial barrier function.
AB  - The endothelial layer of blood vessels controls the passage of cells and solutes
      from the blood into the surrounding tissue. Crucial for this regulation is the
      integrity of endothelial cell-cell junctions. Various molecular mechanisms
      control junctional integrity of the endothelial layer including GTPases,
      modulation of the actomyosin cytoskeleton and phosphorylation and
      dephosphorylation of junctional proteins. Several kinases and phosphatases have
      been identified that are good candidates for the regulation of the endothelial
      barrier function. For some of them, in vivo evidence has recently been presented
      that highlights their importance in either the regulation of vascular
      permeability or leukocyte extravasation. This review will summarize current
      knowledge about the regulation of endothelial junctions by kinases and
      phosphatases. In particular, the role of the endothelial specific phosphatase VE
      PTP in the context of endothelial cell contact stability will be highlighted. 

PMID- 24566521
TI  - Design of prodrugs to enhance colonic absorption by increasing lipophilicity and
      blocking ionization.
AB  - Prodrugs are chemistry-enabled drug delivery modifications of active molecules
      designed to enhance their pharmacokinetic, pharmacodynamic and/or
      biopharmaceutical properties. Ideally, prodrugs are efficiently converted in
      vivo, through chemical or enzymatic transformations, to the active parent
      molecule. The goal of this work is to enhance the colonic absorption of a drug
      molecule with a short half-life via a prodrug approach to deliver sustained
      plasma exposure and enable once daily (QD) dosing. The compound has poor
      absorption in the colon and by the addition of a promoiety to block the
      ionization of the molecule as well as increase lipophilicity, the relative
      colonic absorption increased from 9% to 40% in the retrograde dog colonic model.
      A combination of acceptable solubility and stability in the gastrointestinal
      tract (GI) as well as permeability was used to select suitable prodrugs to
      optimize colonic absorption. 

PMID- 24566522
TI  - Au@Pt nanostructures: a novel photothermal conversion agent for cancer therapy.
AB  - Due to aspect ratio dependent localized surface plasmon resonance (SPR), gold
      nanorods (Au NRs) can be tuned to have a strong absorption in the near infrared
      region (NIR) and convert light to heat energy, which shows promises in cancer
      photothermal therapy. In this study, we introduced another more efficient NIR
      photothermal agent, Au nanorods coated with a shell of Pt nanodots (Au@Pt
      nanostructures). After surface modification with Pt dots, the Au@Pt nanostructure
      became a more efficient photothermal therapy agent as verified both in vitro and
      in vivo. To clarify the mechanism, we assessed the interaction between the MDA-MB
      231 cells with Au@Pt or Au NRs. Results showed that the slightly higher uptake
      and the reduced sensitivity of the longitudinal SPR band on the intracellular
      aggregate state may contribute to the better photothermal efficiency for Au@Pt
      NRs. The theoretical studies further confirmed that the Au@Pt nanostructure
      itself exhibited better photothermal efficiency compared to Au NRs. These
      advantages make the Au@Pt nanostructure a more attractive and effective agent for
      cancer photothermal therapy than general Au NRs. 

PMID- 24566523
TI  - The modulation of grain boundary barrier in ZnMgO/ZnO heterostructure by surface
      polar liquid.
AB  - Modulation of grain boundary barrier in ZnO layer by polar liquid, was
      investigated in ZnMgO/ZnO heterostructures grown by plasma-assisted molecular
      beam epitaxy. Traditionally, surface adsorbates can only affect the surface atoms
      or surface electronic states. However, it was found that the electronic
      conduction property of ZnO far from the surface could be tailored obviously by
      the polar liquid adsorbed on the ZnMgO surface. Physically, this phenomenon is
      supposed to be caused by the electrostatical couple between the liquid polarity
      and the grain boundary barrier in the ZnO layer through crystal polarization
      field. 

PMID- 24566526
TI  - Microgels on-demand.
AB  - Three-dimensional (3D) hydrogel structures are finding use in fundamental studies
      of self-assembly, rheology, and 3D cell culture. Most techniques for 3D hydrogel
      formation are 'single pot', in which gels are not addressable after formation.
      For many applications, it would be useful to be able to form arrays of gels
      bearing mixtures of constituents and/or formed from composites of different gel
      materials. Here, in response to this challenge, we introduce a digital
      microfluidic method for 'on-demand' formation of arrays of microgels bearing
      arbitrary contents and shapes. On formation of the gels, each microgel is
      individually addressable for reagent delivery and analysis. We demonstrate the
      utility of the method for 3D cell culture and higher-order tissue formation by
      implementing the first sub-microlitre recapitulation of 3D kidney
      epithelialization. We anticipate this platform will enable new research that can
      exploit the flexible nature of this technique for forming and addressing arrays
      of hydrogels with unique geometries and contents. 

PMID- 24566528
TI  - Heavily-doped colloidal semiconductor and metal oxide nanocrystals: an emerging
      new class of plasmonic nanomaterials.
AB  - The creation and study of non-metallic nanomaterials that exhibit localized
      surface plasmon resonance (LSPR) interactions with light is a rapidly growing
      field of research. These doped nanocrystals, mainly self-doped semiconductor
      nanocrystals (NCs) and extrinsically-doped metal oxide NCs, have extremely high
      concentrations of free charge carriers, which allows them to exhibit LSPR at near
      infrared (NIR) wavelengths. In this tutorial review, we discuss recent progress
      in developing and synthesizing doped semiconductor and metal oxide nanocrystals
      with LSPR, and in studying the optical properties of these plasmonic
      nanocrystals. We go on to discuss their growing potential for advancing
      biomedical and optoelectronic applications. 

PMID- 24566524
TI  - Prenatal methamphetamine exposure and neurodevelopmental outcomes in children
      from 1 to 3 years.
AB  - BACKGROUND: Despite the evidence that women world-wide are using methamphetamine
      (MA) during pregnancy little is known about the neurodevelopment of their
      children. DESIGN: The controlled, prospective longitudinal New Zealand (NZ)
      Infant Development, Environment and Lifestyle (IDEAL) study was carried out in
      Auckland, NZ. Participants were 103 children exposed to MA prenatally and 107 who
      were not exposed. The Mental Developmental Index (MDI) and the Psychomotor
      Developmental Index (PDI) of the Bayley Scales of Infant Development, Second
      Edition (BSID-II) measured cognitive and motor performances at ages 1, 2 and 3,
      and the Peabody Developmental Motor Scale, Second Edition (PDMS-II) measured
      gross and fine motor performances at 1 and 3. Measures of the child's environment
      included the Home Observation of Measurement of the Environment and the Maternal
      Lifestyle Interview. The Substance Use Inventory measured maternal drug use.
      RESULTS: After controlling for other drug use and contextual factors, prenatal MA
      exposure was associated with poorer motor performance at 1 and 2 years on the
      BSID-II. No differences were observed for cognitive development (MDI). Relative
      to non-MA exposed children, longitudinal scores on the PDI and the gross motor
      scale of the PDMS-2 were 4.3 and 3.2 points lower, respectively. Being male and
      of Maori descent predicted lower cognitive scores (MDI) and being male predicted
      lower fine motor scores (PDMS-2). CONCLUSIONS: Prenatal exposure to MA was
      associated with delayed gross motor development over the first 3 years, but not
      with cognitive development. However, being male and of Maori descent were both
      associated with poorer cognitive outcomes. Males in general did more poorly on
      tasks related to fine motor development.

PMID- 24566527
TI  - Visuospatial working memory in 7- to 12-year-old children with disruptive
      behavior disorders.
AB  - Very little evidence exists on working memory (WM) deficits in children with
      disruptive behavior disorders such as Oppositional Defiant Disorder (ODD) or
      Conduct Disorder (CD). We evaluated the function of visuospatial WM in patients
      (n = 26) with ODD/CD compared with age- and gender-matched controls (n = 26)
      while controlling for the comorbid diagnosis of Attention-Deficit/Hyperactivity
      Disorder (ADHD) in patients. The patients were diagnosed by Kiddie-SADS-PL
      interview, psychiatric symptoms were measured using Child Behavior Checklist and
      Teacher Report Form. WM was measured by computer-based visuospatial n-back tasks
      with three difficulty levels. Incorrect responses (reflecting WM performance) in
      all WM tasks were significantly higher in patients with ODD/CD than in controls.
      Both patient subgroups, ODD/CD + ADHD and ODD/CD alone, had WM deficits compared
      with controls. These results suggest that children with ODD/CD have visuospatial
      WM deficits that are not accounted for by comorbid ADHD.

PMID- 24566529
TI  - Maternal and paternal satisfaction in the delivery room: a cross-sectional
      comparative study.
AB  - OBJECTIVES: Maternal satisfaction during the birthing process has been well
      documented, whereas little is known about the fathers' birth experiences. Our
      objective was to evaluate and compare the birth satisfaction of mothers and
      fathers. DESIGN: Comparative cross-sectional study. SETTING: Number of
      participating centres: one level III maternity centre (2813 births in 2011) in
      Sherbrooke, Quebec, Canada. PARTICIPANTS: 200 mothers and 200 accompanying
      fathers/mother's partner recruited 12-24 h after the birth over a 6-week period.
      PRIMARY AND SECONDARY OUTCOME MEASURES: The Birth Satisfaction Scale (BSS) was
      used for the mother, and it was adapted to the father's perspective. Paired
      samples t tests were used for comparing mothers and fathers for the BSS global
      and thematic scores. Multiple linear regressions (forward stepwise method) were
      made to identify predicting factors of mothers' and fathers' satisfaction.
      RESULTS: Global satisfaction scores for mothers (115.5/150) and fathers
      (114.4/150) were relatively high and similar (p=0.116). The analysis of subthemes
      showed that more distress during childbirth was reported by mothers (p<0.001),
      while less support (p<0.001) and care satisfaction (p<0.001) were reported by
      fathers. The use of epidural anaesthesia during vaginal birth was the sole
      concordant lower satisfaction predictor. For mothers, other satisfaction
      predictors were labour length, tearing and type of anaesthesia used in caesarean
      section. For fathers, lower satisfaction predictors were instrumental delivery,
      primary caesarean delivery and infant's distress factors after caesarean section.
      CONCLUSIONS: This study highlights differences in mothers' and fathers' birth
      satisfaction and in their predictors. It is thus important to take into account
      the birth experience of each parent and to support parents accordingly by
      adapting care provision surrounding childbirth. More research on this topic from
      the prenatal to the postnatal period is suggested, as it might have an impact on
      parents' satisfaction and on early parenthood experience.

PMID- 24566531
TI  - Diagnostic values of soluble mesothelin-related peptides for malignant pleural
      mesothelioma: updated meta-analysis.
AB  - OBJECTIVE: Although the values of soluble mesothelin-related peptides (SMRPs),
      including mesothelin and megakaryocyte potentiating factor, in serum and/or
      pleural fluid for diagnosing malignant pleural mesothelioma (MPM) have been
      extensively studied, the exact diagnostic accuracy of these SMRPs remains
      controversial. The purpose of the present meta-analysis is to update the overall
      diagnostic accuracy of SMRPs in serum and, furthermore, to establish diagnostic
      accuracy of SMRPs in pleural fluid for MPM. DESIGN: Systematic review and meta
      analysis. METHODS: A total of 30 articles of diagnostic studies were included in
      the current meta-analysis. Sensitivity, specificity and other measures of
      accuracy of SMRPs in serum and pleural fluid for the diagnosis of MPM were pooled
      using random effects models. Summary receiver operating characteristic curves
      were used to summarise overall test performance. RESULTS: The summary estimates
      of sensitivity, specificity, positive likelihood ratio, negative likelihood ratio
      and diagnostic OR were 0.61, 0.87, 5.71, 0.43 and 14.43, respectively, for serum
      and 0.79, 0.85, 4.78, 0.30 and 19.50, respectively, for pleural fluid. It was
      also found that megakaryocyte potentiating factor in serum had a superior
      diagnostic accuracy compared with mesothelin for MPM. CONCLUSIONS: SMRPs in both
      serum and pleural fluid are helpful markers for diagnosing MPM with similar
      diagnostic accuracy. The negative results of SMRP determinations are not
      sufficient to exclude non-MPM, and the positive test results indicate that
      further invasive diagnostic steps might be necessary for the diagnosis of MPM.

PMID- 24566532
TI  - Depression and resilience in women with HIV and early life stress: does trauma
      play a mediating role? A cross-sectional study.
AB  - OBJECTIVES: The present study sought to assess the relationship between
      depressive symptomatology and resilience among women infected with HIV and to
      investigate whether trauma exposure (childhood trauma, other discrete lifetime
      traumatic events) or the presence of post-traumatic stress symptomatology
      mediated this relationship. DESIGN: Cross-sectional study. SETTING: Western Cape,
      South Africa. PARTICIPANTS: A convenience sample of 95 women infected with HIV in
      peri-urban communities in the Western Cape, South Africa. All women had exposure
      to moderate-to-severe childhood trauma as determined by the Childhood Trauma
      Questionnaire. PRIMARY AND SECONDARY OUTCOME MEASURES: We examined the
      relationship between depressive symptomatology and resilience (the Connor
      Davidson Resilience Scale) and investigated whether trauma exposure or the
      presence of post-traumatic stress symptomatology mediated this relationship
      through the Sobel test for mediation and PLS path analysis. RESULTS: There was a
      significant negative correlation between depressive symptomatology and resilience
      (p=<0.01). PLS path analysis revealed a significant direct effect between
      depression and resilience. On the Sobel test for mediation, distal (childhood
      trauma) and proximal traumatic events did not significantly mediate this
      association (p=> 0.05). However, post-traumatic stress symptomatology
      significantly mediated the relationship between depression and resilience in
      trauma-exposed women living with HIV. CONCLUSIONS: In the present study, higher
      levels of resilience were associated with lower levels of self-reported
      depression. Although causal inferences are not possible, this suggests that in
      this sample, resilience may act as protective factor against the development of
      clinical depression. The results also indicate that post-traumatic stress
      symptoms (PTSS), which are highly prevalent in HIV-infected and trauma exposed
      individuals and often comorbid with depression, may further explain and account
      for this relationship. Further investigation is required to determine whether
      early identification and treatment of PTSS in this population may ameliorate the
      onset and persistence of major depression.

PMID- 24566535
TI  - Assessment and optimization of autophagy monitoring methods in Arabidopsis roots
      indicate direct fusion of autophagosomes with vacuoles.
AB  - Autophagy is a degradation pathway that recycles cell materials upon encountering
      stress conditions or during specific developmental processes. To better
      understand the physiological roles of autophagy, proper monitoring methods are
      very important. In mammals and yeast, monitoring of autophagy is often performed
      with a green fluorescent protein (GFP)-ATG8 fusion protein or with acidotropic
      dyes such as monodansylcadaverine (MDC) and LysoTracker Red (LTR). To evaluate
      these monitoring methods, here we examined these systems by inducing autophagy in
      Arabidopsis thaliana roots as a model for monitoring autophagy in planta. Under
      carbon- and nitrogen-starved conditions, the number and size of vesicles labeled
      by GFP-ATG8 was increased for several hours and then gradually decreased to a
      level higher than that observed before the start of the experiment. We also
      observed the disappearance of GFP-ATG8-labeled vesicles after treatment with
      wortmannin, a phosphatidylinositol 3-kinase inhibitor known as an autophagy
      inhibitor, showing that the GFP-ATG8 transgenic line constitutes an excellent
      method for monitoring autophagy. These data were compared with plants stained
      with MDC and LTR. There was no appreciable MDC/LTR staining of small organelles
      in the root under the induction of autophagy. Some vesicles were eventually
      observed in the root tip only, but co-localization experiments, as well as
      experiments with autophagy-deficient atg mutants, provided the evidence that
      these structures were located in the vacuole and were not manifestly
      autophagosomes and/or autolysosomes. Extreme caution should therefore be used
      when monitoring autophagy with the aid of MDC/LTR. Additionally, our observations
      strongly suggest that autophagosomes fuse directly to vacuoles in Arabidopsis
      roots. 

PMID- 24566537
TI  - Effect of angiotensin I-converting enzyme and alpha-actinin-3 gene polymorphisms
      on sport performance.
AB  - Genetic polymorphism is considered to be associated with human physical
      performance. The angiotensin I-converting enzyme insertion/deletion (ACE I/D) and
      the alpha-actinin-3 gene (ACTN3) R577X polymorphisms have been widely
      investigated for such associations, and functional ACE I/D and ACTN3 R577X
      polymorphisms have been associated with sprinter performance. The aim of this
      study was to determine the effect of these polymorphisms on sport performance
      among 37 elite athletes and 37 healthy controls. The ACE II genotype was
      identified in 32.43% of the control group and 8.11% of elite athletes, the DD
      genotype in 37.84% of the control group and 51.35% of the elite athletes, and the
      ID genotype in 29.73% of the control group and 40.54% of the elite athletes. With
      regard to the ACTN3 gene, the XX genotype, which confers an advantage for
      endurance activities, was identified in 10.81% of the control group and 35.14% of
      the elite athletes. The XX genotype was observed more frequently than the RR
      genotype (advantageous for sprinting), which was identified in 2.70% of the
      control group and 10.81% of elite athletes. The RX genotype (observed in 86.48%
      of the control group and in 54.05% of the elite athletes) was the most common
      genotype of the individuals in the present study. The study showed that ACTN3 and
      ACE gene polymorphisms have an effect on muscle power; however, larger studies
      are required.

PMID- 24566538
TI  - Dorsal vascularized grafting for scaphoid nonunion: a comparison of two surgical
      techniques.
AB  - OBJECTIVES: To compare the radiographic and functional outcomes of 2 surgical
      techniques for treating scaphoid nonunion. DESIGN: Randomized prospective study.
      PATIENTS/PARTICIPANTS: Researchers assessed the outcomes every 2 weeks until bone
      healing and at discharge. INTERVENTIONS: (1) Vascularized bone grafting (VBG)
      using the 1, 2 intercompartmental suprareticular artery and (2) a distal radius
      nonvascularized bone graft. MAIN OUTCOMES/INTERVENTIONS: Time to union (primary),
      union rate, and functional outcomes. RESULTS: Seventy-five patients were followed
      for 29 months; 2 were lost to final follow-up. Both groups had similar baseline
      characteristics. The VBG group reached bone union earlier by 12 days (P = 0.002),
      but union rates were similar (P = 0.312). There was also less ulnar deviation in
      the VBG group (P = 0.03). There were no other differences between either
      intervention groups. CONCLUSIONS: Although the VBG group attained earlier union,
      this may not be clinically meaningful, nor justify the greater technical
      difficulty and use of resources associated with this intervention. LEVEL OF
      EVIDENCE: Therapeutic Level II. See instructions for authors for a complete
      description of levels of evidence.

PMID- 24566536
TI  - Singlet oxygen production by PSII under light stress: mechanism, detection and
      the protective role of beta-carotene.
AB  - In this review, I outline the indirect evidence for the formation of singlet
      oxygen ((1)O(2)) obtained from experiments with the isolated PSII reaction center
      complex. I also review the methods we used to measure singlet oxygen directly,
      including luminescence at 1,270 nm, both steady state and time resolved. Other
      methods we used were histidine-catalyzed molecular oxygen uptake (enabling
      (1)O(2) yield measurements), and dye bleaching and difference absorption
      spectroscopy to identify where quenchers of (1)O(2) can access this toxic
      species. We also demonstrated the protective behavior of carotenoids bound within
      Chl-protein complexes which bring about a substantial amount of (1)O(2) quenching
      within the reaction center complex. Finally, I describe how these techniques have
      been used and expanded in research on photoinhibition and on the role of (1)O(2)
      as a signaling molecule in instigating cellular responses to various stress
      factors. I also discuss the current views on the role of (1)O(2) as a signaling
      molecule and the distance it might be able to travel within cells.

PMID- 24566539
TI  - A special issue on 'Cancer'.

PMID- 24566540
TI  - Gastrointestinal hormones and the dialogue between gut and brain.
AB  - The landmark discovery by Bayliss and Starling in 1902 of the first hormone,
      secretin, emerged from earlier observations that a response (pancreatic
      secretion) following a stimulus (intestinal acidification) occurred after section
      of the relevant afferent nerve pathway. Nearly 80 years elapsed before it became
      clear that visceral afferent neurons could themselves also be targets for gut and
      other hormones. The action of gut hormones on vagal afferent neurons is now
      recognised to be an early step in controlling nutrient delivery to the intestine
      by regulating food intake and gastric emptying. Interest in these mechanisms has
      grown rapidly in view of the alarming global increase in obesity. Several of the
      gut hormones (cholecystokinin (CCK); peptide YY3-36 (PYY3-36); glucagon-like
      peptide-1 (GLP-1)) excite vagal afferent neurons to activate an ascending pathway
      leading to inhibition of food intake. Conversely others, e.g. ghrelin, that are
      released in the inter-digestive period, inhibit vagal afferent neurons leading to
      increased food intake. Nutrient status determines the neurochemical phenotype of
      vagal afferent neurons by regulating a switch between states that promote
      orexigenic or anorexigenic signalling through mechanisms mediated, at least
      partly, by CCK. Gut-brain signalling is also influenced by leptin, by gut
      inflammation and by shifts in the gut microbiota including those that occur in
      obesity. Moreover, there is emerging evidence that diet-induced obesity locks the
      phenotype of vagal afferent neurons in a state similar to that normally occurring
      during fasting. Vagal afferent neurons are therefore early integrators of
      peripheral signals underling homeostatic mechanisms controlling nutrient intake.
      They may also provide new targets in developing treatments for obesity and
      feeding disorders.

PMID- 24566541
TI  - In vivo and in vitro biophysical properties of hair cells from the lateral line
      and inner ear of developing and adult zebrafish.
AB  - Hair cells detect and process sound and movement information, and transmit this
      with remarkable precision and efficiency to afferent neurons via specialized
      ribbon synapses. The zebrafish is emerging as a powerful model for genetic
      analysis of hair cell development and function both in vitro and in vivo.
      However, the full exploitation of the zebrafish is currently limited by the
      difficulty in obtaining systematic electrophysiological recordings from hair
      cells under physiological recording conditions. Thus, the biophysical properties
      of developing and adult zebrafish hair cells are largely unknown. We investigated
      potassium and calcium currents, voltage responses and synaptic activity in hair
      cells from the lateral line and inner ear in vivo and using near-physiological in
      vitro recordings. We found that the basolateral current profile of hair cells
      from the lateral line becomes more segregated with age, and that cells positioned
      in the centre of the neuromast show more mature characteristics and those towards
      the edge retain a more immature phenotype. The proportion of mature-like hair
      cells within a given neuromast increased with zebrafish development. Hair cells
      from the inner ear showed a developmental change in current profile between the
      juvenile and adult stages. In lateral line hair cells from juvenile zebrafish,
      exocytosis also became more efficient and required less calcium for vesicle
      fusion. In hair cells from mature zebrafish, the biophysical characteristics of
      ion channels and exocytosis resembled those of hair cells from other lower
      vertebrates and, to some extent, those in the immature mammalian vestibular and
      auditory systems. We show that although the zebrafish provides a suitable animal
      model for studies on hair cell physiology, it is advisable to consider that the
      age at which the majority of hair cells acquire a mature-type configuration is
      reached only in the juvenile lateral line and in the inner ear from >2 months
      after hatching.

PMID- 24566544
TI  - Ondansetron for acute gastroenteritis: a failure of knowledge translation.

PMID- 24566542
TI  - A 'calcium capacitor' shapes cholinergic inhibition of cochlear hair cells.
AB  - Efferent cholinergic neurons project from the brainstem to inhibit sensory hair
      cells of the vertebrate inner ear. This inhibitory synapse combines the activity
      of an unusual class of ionotropic cholinergic receptor with that of nearby
      calcium-dependent potassium channels to shunt and hyperpolarize the hair cell.
      Postsynaptic calcium signalling is constrained by a thin near-membrane cistern
      that is co-extensive with the efferent terminal contacts. The postsynaptic
      cistern may play an essential role in calcium homeostasis, serving as sink or
      source, depending on ongoing activity and the degree of buffer saturation.
      Release of calcium from postsynaptic stores leads to a process of retrograde
      facilitation via the synthesis of nitric oxide in the hair cell. Activity
      dependent synaptic modification may contribute to changes in hair cell
      innervation that occur during development, and in the aged or damaged cochlea. 

PMID- 24566545
TI  - Chemical imaging of artificial fingerprints by desorption electro-flow focusing
      ionization mass spectrometry.
AB  - Desorption electro-flow focusing ionization (DEFFI) mass spectrometry was used to
      image chemical distributions of endogenous, e.g., fatty acids, and trace
      exogenous compounds, e.g., explosives, narcotics and lotions, in deposited and
      lifted artificial fingerprints, directly from forensic lift tape. An artificial
      fingerprint mold and synthetic fingerprint material were incorporated for the
      controlled deposition of material for technique demonstration and evaluation. 

PMID- 24566543
TI  - Adaptive changes in the motor cortex during and after longterm forelimb
      immobilization in adult rats.
AB  - Experimental and clinical studies have attempted to evaluate the changes in
      cortical activity seen after immobilization-induced longterm sensorimotor
      restriction, although results remain controversial. We used intracortical
      microstimulation (ICMS), which provides topographic movement representations of
      the motor areas in both hemispheres with optimal spatial characterization,
      combined with behavioural testing to unravel the effects of limb immobilization
      on movement representations in the rat primary motor cortex (M1). Unilateral
      forelimb immobilization in rats was achieved by casting the entire limb and
      leaving the cast in place for 15 or 30 days. Changes in M1 were bilateral and
      specific for the forelimb area, but were stronger in the contralateral-to-cast
      hemisphere. The threshold current required to evoke forelimb movement increased
      progressively over the period in cast, whereas the forelimb area size decreased
      and the non-excitable area size increased. Casting resulted in a redistribution
      of proximal/distal movement representations: proximal forelimb representation
      increased, whereas distal representation decreased in size. ICMS after cast
      removal showed a reversal of changes, which remained partial at 15 days. Local
      application of the GABAA-antagonist bicuculline revealed the impairment of
      cortical synaptic connectivity in the forelimb area during the period of cast and
      for up to 15 days after cast removal. Six days of rehabilitation using a rotarod
      performance protocol after cast removal did not advance map size normalization in
      the contralateral-to-cast M1 and enabled the cortical output towards the distal
      forelimb only in sites that had maintained their excitability. These results are
      relevant to our understanding of adult M1 plasticity during and after
      sensorimotor deprivation, and to new approaches to conditions that require
      longterm limb immobilization.

PMID- 24566546
TI  - The anti-inflammatory and antioxidant effects of pravastatin and nebivolol in rat
      aorta.
AB  - OBJECTIVE: The aim of this study was to investigate the effects of pravastatin
      and nebivolol in the atherosclerotic process including inflammation and oxidative
      stress in rat aorta. METHODS: This experimental randomized controlled study
      comprised of 35 Wistar albino rats. Nomega-nitro-L-arginine methyl ester (L-NAME)
      - induced vascular inflammation and arteriosclerosis were treated with both of
      the pharmacologic agents. All were divided into 5 equal groups: the control,
      group I: L-NAME -15 days, group II: L-NAME 30+ nebivolol, group III: L-NAME -30+
      pravastatin, group IV: L-NAME - 30 days. Serum ceruloplasmin, uric acid, total
      antioxidant capacity (TAC), total cholesterol (T.Chol), low density lipoprotein
      (LDL), high density lipoprotein (HDL), triglyceride (TG) were analyzed. Medial
      thickening and leukocyte infiltration status were examined histopathologically.
      The results were compared with control group and with each other using Kruskal
      Wallis and Mann-Whitney U test. RESULTS: Pravastatin diminished the rise of
      ceruloplasmin, which was taken as an index of inflammation (p=0.002). Pravastatin
      and nebivolol decreased the L-NAME induced oxidative stress (p =0.001, 0.002,
      respectively). Nebivolol diminished the rise of LDL (p=0.04). Pravastatin lowered
      T.Chol, LDL and TG levels (p=0.001, 0.008, 0.040, respectively). HDL values were
      not changed significantly. CONCLUSION: In conclusion, 15 days of statin therapy
      attenuated vascular inflammation and lowered the rised lipid levels (LDL,
      T.cholesterol and TG). Both the nebivolol and pravastatin exhibited antioxidant
      property. These documented beneficial effects of both of the drugs may improve
      the clinical outcomes of patients with hypertension or hyperlipidemia by
      additional studies.

PMID- 24566547
TI  - Effects of valsartan treatment on serum ghrelin level and left ventricular mass
      index in patients with untreated primary hypertension.
AB  - OBJECTIVE: In the present study, left ventricular hypertrophy and serum ghrelin
      concentration in patients with primary hypertension and effects of angiotensin
      receptor blocker valsartan on these parameters were determined. METHODS: Thirty
      seven patients and 30 age and body mass index matched healthy controls were
      followed up prospectively. Serum ghrelin level was measured by enzyme immunoassay
      (EIA). Left ventricular mass was determined by transthoracic echocardiography.
      Left ventricular mass index (LVMI) was calculated by dividing the left
      ventricular mass to body surface area. All patients were started treatment with
      oral valsartan 80 mg. Follow-up visits were performed every 4 weeks, and the
      dosage was doubled in subjects with insufficient blood pressure reduction. At the
      end of the 12th week all measurements were repeated in the patient group. All
      data were recorded in the computer using SPSS for Windows software. Mann-Whitney
      U, Student t, Wilcoxon and t tests were used for statistical analyses. RESULTS:
      At baseline, mean serum ghrelin level was significantly lower in the patients
      group (14.9 ng/mL) compared to healthy controls (42.1 ng/mL) (p<0.05). After a 12
      week antihypertensive treatment of patients, serum ghrelin concentration
      increased while LVMI decreased (p<0.05, for both). No significant correlation was
      found between Delta-ghrelin level and Delta-LVMI (r=0.155, p=0.368). CONCLUSION:
      Low circulating level of ghrelin in patients with hypertension and its increase
      after antihypertensive treatment suggest that this peptide need to be explored in
      the mechanism and complications of hypertension.

PMID- 24566549
TI  - Beta-myosin heavy-chain mutations R403QLW, V606M, K615N and R663H in patients
      with hypertrophic cardiomyopathy.
AB  - OBJECTIVE: Hypertrophic cardiomyopathy (HCM) is a disease of the myocardium with
      an autosomal-dominant pattern of inheritance mainly caused by single heterozygous
      mutations in sarcomere genes. In this study we aimed to detect the presence of
      R403QLW, V606M, K615N, and R663H mutations in beta-myosin heavy-chain gene (MYH7)
      and figure out the genotype-phenotype correlations in Turkish patients with HCM.
      METHODS: This case-control study based on genotype-phenotype correlation included
      69 patients (mean age, years: 50+/-13.16) diagnosed with HCM constituting the
      study group and 50 healthy individuals (mean age, years: 52+/-1.4) constituting
      the control group. DNA was extracted from peripheral blood and the genotyping of
      mutations was performed by real-time PCR technique and high resolution melting
      analysis. Associations between categoric variables were determined using chi
      square tests. Differences between two groups were compared with unpaired
      Student's t-test for continuous variables. RESULTS: None of the patients in the
      HCM group were carrying the index mutations. One healthy individual was found to
      be heterozygous for the R663H mutation with mildly abnormal IVS and LVPW
      thickness. The allele frequency for R663H (G>A) mutation was found to be 0.01% in
      control group. CONCLUSION: We performed a mutational screening of 6 HCM
      associated mutations in 69 Turkish HCM patients (not previously studied except
      R403Q). There was no significant difference in the prevalence of the mutations
      between the patients with HCM and the healthy controls (p>0.05).

PMID- 24566550
TI  - Association of P wave dispersion and left ventricular diastolic dysfunction in
      non-dipper and dipper hypertensive patients.
AB  - OBJECTIVE: Objective of this study was to investigate the correlation between P
      wave dispersion and left ventricular diastolic function, which are associated
      with the increased cardiovascular events in patients with dipper and non-dipper
      hypertensive (HT). METHODS: Eighty sex and age matched patients with dipper and
      non-dipper HT, and 40 control subject were included in this observational cross
      sectional study. P wave dispersion was measured through electrocardiography
      obtained during the admission. The left ventricular LV ejection fraction was
      measured using the modified Simpson's rule by echocardiography. In addition,
      diastolic parameters including E/A rate, deceleration time (DT) and isovolumetric
      relaxation time (IVRT) were recorded. Independent samples Bonferroni, Scheffe and
      Tamhane tests and correlation test (Spearman and Pearson) were used for
      statistical analysis. RESULTS: P wave dispersion was found to be significantly
      increased in the non-dipper than in the dipper group (56.0+/-5.6 vs. 49.1+/-5.3,
      p<0.001). Pmax duration was found significantly higher (115.1+/-5.6 vs. 111.1+/
      5.8, p=0.003) and Pmin duration significantly lower (59.0+/-5.6 vs. 62.3+/-5.3,
      p=0.009) in the non-dippers. Correlation analysis demonstrated presence of
      moderate but significant correlation between P-wave dispersion and left
      ventricular mass index (r=0.412, p=0.011), IVRT (r=0.290 p=0.009), DT (r=0.210,
      p=0.052) and interventricular septum thickness (r=0.230 p=0.04). CONCLUSION: P
      wave dispersion and P Max were found to be significantly increased and P min
      significantly decreased in the non-dipper HT patients compared to the dipper HT
      patients. P-wave dispersion is associated with left ventricular dysfunction in
      non-dipper and dipper HT.

PMID- 24566551
TI  - Effect of left ventricular diastolic dysfunction on left atrial appendage
      function and thrombotic potential in nonvalvular atrial fibrillation.
AB  - OBJECTIVE: We aimed to investigate effects of left ventricular diastolic
      dysfunction on left atrial appendage functions, spontaneous echo contrast and
      thrombus formation in patients with nonvalvular atrial fibrillation. METHODS: In
      58 patients with chronic nonvalvular atrial fibrilation and preserved left
      ventricular systolic function, left atrial appendage functions, left atrial
      spontaneous echo contrast grading and left ventricular diastolic functions were
      evaluated using transthoracic and transoesophageal echocardiogram. Patients
      divided in two groups: Group D (n=30): Patients with diastolic dysfunction, Group
      N (n=28): Patients without diastolic dysfunction. Categorical variables in two
      groups were evaluated with Pearson's chi-square or Fisher's exact test. The
      significance of the lineer correlation between the degree of spontaneous echo
      contrast (SEC) and clinical measurements was evaluated with Spearman's
      correlation analysis. RESULTS: Peak pulmonary vein D velocity of the Group D was
      significantly higher than the Group N (p=0.006). However, left atrial appendage
      emptying velocity, left atrial appendage lateral wall velocity, peak pulmonary
      vein S, pulmonary vein S/D ratio were found to be significantly lower in Group D
      (p=0.028, p<0.001, p<0.001; p<0.001). Statistically significant negative
      correlation was found between SEC in left atrium and left atrial appendage
      emptying, filling, pulmonary vein S/D levels and lateral wall velocities
      respectively (r=-0.438, r=-0.328, r=-0.233, r=-0.447). Left atrial appendage
      emptying, filling, pulmonary vein S/D levels and lateral wall velocities were
      significantly lower in SEC 2-3-4 than SEC 1 (p=0.003, p=0.029, p<0.001, p=0.002).
      CONCLUSION: In patients with nonvalvular atrial fibrillation and preserved left
      ventricular ejection fraction, left atrial appendage functions are decreased in
      patients with left ventricular diastolic dysfunction. Left ventricular diastolic
      dysfunction may constitute a potential risk for formation of thrombus and stroke.

PMID- 24566552
TI  - The effect of long-term continuous positive airway pressure treatment on systolic
      and diastolic function in patients with obstructive sleep apnoea syndrome: a five
      year observational study.
AB  - OBJECTIVE: Evaluation of the long-term effects of continuous positive airway
      presure (CPAP) on mean heart rate and left ventricular systolic and diastolic
      parameters in obstructive sleep apnea syndrome (OSAS) using conventional and
      tissue Doppler techniques. METHODS: This prospective cohort study is designed to
      evaluate the long-term effects of CPAP treatments in normotensive OSAS patients.
      Initially 40 patients aged from eighteen to fifty five with documented OSAS
      syndrome were evaluated within one month of CPAP treatment. All had high self
      reported compliance with treatment. From the latter, 21 patients with
      uninterrupted CPAP therapy (for at least 5 years, 5 hours per day) were included
      in the study and further evaluated with treatment. The left ventricular systolic
      function was assessed on apical four- chamber view using modified Simpson method
      and diastolic function was evaluated with classic transmitral pulsed and tissue
      Doppler techniques. Paired t test and Wilcoxon signed rank test had been used to
      compare the clinical and echocardiography data before and after treatment period.
      RESULTS: A comparison of values assessed after one month and after 5 years of
      CPAP therapy, revealed a significant increase in the acceleration time(AT) Em/Am
      ratio and ejection time (ET) (AT: p=0.04; Em/Am ratio p=0.03 ET: p=0.04) while a
      significant decrease was observed on deceleration time (DT), isovolumetric
      relaxation time (IRT), myocardial performance index (MPI), mitral regurgitation
      (MR) and 24 hour mean heart rate (HR) in all subjects (DT: p=0.02; IVRT: p=0,04;
      MPI: p=0,01; MR: p<=0.001; HR: p=0.004). CONCLUSION: We observed a significant
      improvement in the left ventricular systolic and diastolic function and a
      significant decrease of 24-hour heart rate and mitral regurgitation with
      unchanged ejection fraction of the left ventricle with long-term CPAP treatment
      similar to short-term treatment studies. The long-term maintenance of the
      beneficial effect of CPAP throughout the 5 year long-term treatment can be one of
      the pathophysiologic mechanisms that may explain the decrease of cardiovascular
      mortality observed with long-term CPAP therapy in OSAS patients.

PMID- 24566553
TI  - Prognostic significance of sICAM-1 and sVCAM-1 molecules for cardiac surgery in
      pediatric patients with pulmonary hypertension.
AB  - OBJECTIVE: To investigate preoperative and postoperative blood levels of soluble
      intercellular and vascular cell adhesion molecules (sICAM-1, sVCAM-1) in patients
      with and without pulmonary hypertension (PAH) due to congenital heart disease and
      left to right (L-R) shunt and to determine whether these molecules can be used as
      reliable prognostic markers of endothelial activity to predict surgical outcomes.
      METHODS: In this observational prospective cohort study; 42 patients, operated
      for L-R shunt were divided into three groups. Group 1: L-R shunt without PAH,
      Group 2: L-R shunt with PAH, Group 3: L-R shunt with PAH and postoperative low
      cardiac output syndrome (LCOS). Their sICAM-1 and sVCAM-1 levels were measured
      preoperatively (sICAM-0, sVCAM-0) and on the first (sICAM-1, sVCAM-1) and fifth
      postoperative days (sICAM-2, sVCAM-2).ROC curve for various cut-off levels of
      sICAM 0, sVCAM 0 in differentiating PAH patients with and without LCOS. RESULTS:
      In Group 3, sICAM-0 and sVCAM-2 levels were higher than Group 1 and 2. The ROC
      curve demonstrated a significant association between sICAM-0 in patients with L-R
      shunt and PAH (Group 2 and 3) and the development of LCOS (area under the curve:
      0.98, p<0.01 and 0.97, p<0.01, respectively). At a sICAM 0 concentration >359
      ng/mL, there was a sensitivity of 90% and specificity of 95% for identification
      of LCOS in patients with L-R shunt and PAH (AUC: 0.98, 95% CI: 0.95-1.02,
      p<0.01).CONCLUSION: High preoperative sICAM-1 molecule may be used to predict
      postoperative dichotomous outcome in patients with PAH associated with L-R shunt.

PMID- 24566554
TI  - Diagnostic accuracy of Doppler ultrasonography for assessment of internal
      thoracic artery graft patency.
AB  - OBJECTIVE: The main purpose of this study was to assess the patency of left
      internal thoracic artery (LITA) graft by using color Doppler ultrasonography
      (CDUSG) and furthermore to determine the sensitivity and specificity of CDUSG for
      patency by using coronary angiography as the reference standard. METHODS: This
      study is an observational cohort study on diagnostic accuracy that was held
      between August 2008 and October 2009. CDUSG was performed in 138 consecutive
      patients who had angina symptom or positive ischemic findings following coronary
      artery bypass surgery. LITA blood flow velocity at peak-systole (PSV), diastole
      (PDV) and end-diastole (EDV) was recorded. All patients were also assessed by
      coronary angiography for LITA graft patency. Statistical analysis was performed
      by using independent samples t-test, Mann-Whitney U test, chi-square test and
      receiver operating curve analyses (ROC). RESULTS: Seventy-eight of all patients
      had functional LITA grafts and 59 patients had dysfunctional LITA grafts
      according to CDUSG-derived parameters, whereas we cannot conclude about one
      patient's LITA graft functionality. The LITA grafts were visualized
      angiographically in all cases. Of all 138 patients, 60 patients had dysfunctional
      LITA grafts after angiographic evaluation. The ROC analyses showed that PDV
      (AUC=0.899, 95% CI 0.844 to 0.953; p<0.001) and EDV (AUC=0.900; 95% CI 0.847 to
      0.953; p<0.001) values were also strongly associated with graft functionality. We
      found out that CDUSG predicts LITA graft functionality with a sensitivity and
      specificity of 100% and 98.4% respectively. The accuracy of the CDUSG was
      calculated as 99.3%. CONCLUSION: CDUSG is a reliable non-invasive method for
      assessment of LITA graft patency.

PMID- 24566555
TI  - Almanac 2013: heart failure.

PMID- 24566556
TI  - Filamentous Escherichia coli cells swimming in tapered microcapillaries.
AB  - This study analyzed the swimming characteristics of filamentous Escherichia coli
      cells inside tapered capillaries with a diameter decreasing from 700 MUm to 4 MUm
      and a mean body length of 27.8 MUm +/- 11.9 MUm. Cells that were pre-oriented
      towards the narrower diameter section of the tapered capillary swam with high
      directional persistence, following conical-helix trajectories along the capillary
      wall. The confinement of the tapered capillary significantly diminished the mean
      swimming speed of filamentous cells when compared to their unrestricted mean
      swimming speed. The cell body rotation of individual filamentous bacteria
      decreased along the tapered direction, likely due to increased steric
      interactions with the capillary wall. Filamentous cells that swam under imposed
      flow rates ranging from 0.2 MUl/min to 0.8 MUl/min showed positive rheotaxis
      inside the 150 MUm-350 MUm diameter region of the tapered capillary. Depending on
      the imposed flow rate, none of the bacteria could advance beyond a critical
      diameter in the tapered capillary. This critical diameter is likely to be the
      position of the maximum shear rate they can tolerate without being flushed away.
      This work showed experimental evidence of how a simple flow constriction such as
      a tapered tube forms a hydrodynamic barrier that can deter the advance of
      bacterial rheotaxis. 

PMID- 24566557
TI  - Image transport through a disordered optical fibre mediated by transverse
      Anderson localization.
AB  - Transverse Anderson localization of light allows localized optical-beam-transport
      through a transversely disordered and longitudinally invariant medium. Its
      successful implementation in disordered optical fibres recently resulted in the
      propagation of localized beams of radii comparable to that of conventional
      optical fibres. Here we demonstrate optical image transport using transverse
      Anderson localization of light. The image transport quality obtained in the
      polymer disordered optical fibre is comparable to or better than some of the best
      commercially available multicore image fibres with less pixelation and higher
      contrast. It is argued that considerable improvement in image transport quality
      can be obtained in a disordered fibre made from a glass matrix with near
      wavelength-size randomly distributed air-holes with an air-hole fill-fraction of
      50%. Our results open the way to device-level implementation of the transverse
      Anderson localization of light with potential applications in biological and
      medical imaging. 

PMID- 24566558
TI  - Copper beaten skull in X-linked hypophosphataemic rickets.

PMID- 24566559
TI  - Homelessness, behavioral health disorders and intimate partner violence: barriers
      to services for women.
AB  - Homeless women comprise a significant portion of the homeless population and may
      encounter multiple life stressors including mental illness, substance abuse, and
      trauma. Women who are homeless may experience difficulty gaining access to
      resources such as shelter and health care. In addition, the interaction of
      behavioral health problems with intimate partner violence (IPV) may create
      extraordinary barriers to their engagement in services. This paper explores the
      co-occurrence of homelessness, behavioral health problems, and IPV and lessons
      learned through a gender-specific homeless services program designed to reach
      women who are unengaged in traditional services. Recommendations for providing
      gender-responsive services are discussed. 

PMID- 24566560
TI  - A 12-week weight reduction intervention for overweight individuals taking
      antipsychotic medications.
AB  - People taking antipsychotic medications are at increased risk for obesity,
      diabetes, and early mortality. Few weight loss interventions have targeted this
      population. Thirty-six individuals were randomized to an evidence-based 12-week
      weight loss intervention (PREMIER with DASH diet, n = 18) or to usual care (n =
      18) in this feasibility trial. Average attendance was 8.6 of 12 sessions. Intent
      to-treat analyses of covariance, adjusted for baseline weight, showed significant
      changes in weight: Mean weight in intervention participants declined from 213.3
      to 206.6 pounds, while control participants' weight was unchanged. It is possible
      to recruit, assess, intervene with, and retain participants taking antipsychotic
      medications in a dietary and exercise lifestyle change trial. Participants
      reported high levels of satisfaction with the intervention. 

PMID- 24566562
TI  - Alopecia in genetic diseases.
AB  - Congenital abnormalities of the hair shaft are conditions in most cases linked to
      chemical, biochemical, and morphological alterations, genetically determined.
      These alterations may be associated with a larger array of symptoms, as mentioned
      above, or may occur isolated. The number of genes involved and their penetration
      are responsible for the mode of transmission, severity, and phenotypic expression
      of the disease. Furthermore, in some cases, these abnormalities can be considered
      true pathognomonic markers of disease. Within this disorder, two groups are
      classically identified: with increased fragility of the hair shaft and without
      increased fragility. Congenital abnormalities of the hair shaft that present an
      increased fragility of hair include: Trichorrhexis nodosa congenita,
      Trichoschisis, Trichorrhexis invaginata, Trichothiodystrophy, Trichoclasia, Pili
      torti, Monilethrix and Loose anagen syndrome; while the alterations that are not
      associated with a greater fragility of the hair are: Pili annulati, Longitudinal
      grooves, Uncombable hair syndrome (Pili trianguli et canaliculi), Woolly hair,
      Woolly hair with dominant inheritance, Familial recessive woolly hair and Woolly
      hair nevus. 

PMID- 24566561
TI  - Functional transformations of bile acid transporters induced by high-affinity
      macromolecules.
AB  - Apical sodium-dependent bile acid transporters (ASBT) are the intestinal
      transporters that form intermediate complexes with substrates and its
      conformational change drives the movement of substrates across the cell membrane.
      However, membrane-based intestinal transporters are confined to the transport of
      only small molecular substrates. Here, we propose a new strategy that uses high
      affinity binding macromolecular substrates to functionally transform the membrane
      transporters so that they behave like receptors, ultimately allowing the apical
      basal transport of bound macromolecules. Bile acid based macromolecular
      substrates were synthesized and allowed to interact with ASBT.
      ASBT/macromolecular substrate complexes were rapidly internalized in vesicles,
      localized in early endosomes, dissociated and escaped the vesicular transport
      while binding of cytoplasmic ileal bile acid binding proteins cause exocytosis of
      macromolecules and prevented entry into lysosomes. This newly found
      transformation process of ASBT suggests a new transport mechanism that could aid
      in further utilization of ASBT to mediate oral macromolecular drug delivery. 

PMID- 24566563
TI  - Androgenetic alopecia.
AB  - Androgenetic alopecia (AGA) is the most common form of alopecia, affecting up to
      80% of men and 50% of women in the course of their life. AGA is caused by a
      progressive reduction in the diameter, length and pigmentation of the hair. Hair
      thinning results from the effects of the testosterone metabolite
      dehydrotestosterone (DHT) on androgen-sensitive hair follicles. In women, AGA
      produces diffuse thinning of the crown region with maintenance of the frontal
      hairline (Ludwig pattern AGA). In premenopausal women, AGA can be a sign of
      hyperandrogenism, together with hirsutism and acnes. Male pattern is
      characterized by bitemporal recession of the frontal hairline, followed by
      diffuse thinning at the vertex. Today, scalp dermoscopy is used routinely in
      patients with androgenetic alopecia, as it facilitates the diagnosis and
      differential diagnosis with other diseases, allows staging of severity, and
      allows you to monitor the progress of the disease in time and response to
      treatment. AGA is a progressive disease that tends to worsen with time. Medical
      treatment of AGA includes topical minoxidil, antiandrogen agents, 5-alpha
      reductase inhibitors. 

PMID- 24566564
TI  - Alopecia Areata: news on diagnosis, pathogenesis and treatment.
AB  - This review focuses on recent changes in the clinical, pathogenetic and
      therapeutic developments with regards to Alopecia Areata. Some new clinical forms
      and some phenomena have been described for the first time in recent years.
      Several phenomena previously observed such as the Renbok, the Koebner and the
      possibility that an exclamation mark hair can resume its physiological growth
      have been confirmed. The pathogenetic role of cytotoxic cells is increasingly
      evident, as well as the deficit of cells and the factors regulating the
      autoimmune response. The concept of immune privilege of the hair follicle has had
      further confirmation and have been identified some of the molecular mechanisms
      such as the expression of the receptors for killer lymphocytes on the
      trichokeratinocytes of the Outer Root Sheat. There is a renewed interest on the
      possible role of mast cell as a key element in the acute and chronic phases of
      the disease. New therapies are focused on the inhibition of the killer cells
      directed against antigens not yet fully specified of the hair follicle and on the
      restoration of the immune privilege of this structure. Alopecia Areata is a
      disease with high emotional impact, able to reduce the quality of life of
      patients and their family entourage. It is often frustrating for those affected
      and for the therapists due to its evolution quite unpredictable and the mixed
      response to the few validated therapies. Investment in research originate almost
      exclusively from voluntary associations of patients, which need to be known and
      supported.

PMID- 24566565
TI  - Telogen effluvium revisited.
AB  - Telogen effluvium (TE) is heterogeneous disorder. It can be classified into three
      main categories: the premature teloptosis, the collective teloptosis and the
      premature entry into telogen. The last category can be divided in three types:
      the drug induced TE, TE due to dietary deficiencies and the "autoimmune" TE.
      Despite this heterogeneity, the large majority of TE that arrive at the
      dermatologist's observation pertain to the autoimmune type, featuring a standard
      presentation. The typical patient is a woman claiming to have always had a "full
      head of hair" and reporting her hair to come out suddenly "by the handful".
      Usually, she is accurate about the date of onset of her shedding. She is in good
      health, without signs of anorexia nor nutrient deficiencies. She admits to having
      been in an anxious state for some months, and felt, occasionally or not, a
      painful or burning sensation at the scalp (trichodynia). Usually, the course of
      the disorder is chronic but intermittent, with apparent remissions being
      irregularly intermitted by relapses. The shed hairs do not exhibit telogen roots,
      but mostly exogen ones. This distinct entity, shares some analogies with alopecia
      areata, including the triggering role of emotional stress, trichodynia and the
      frequent association with Hashimoto's thyroiditis. Methods to assess its severity
      and to monitor treatment are described. In the absence of a documented
      etiopathogenesis, no treatment can be endorsed, but a course of topical
      corticosteroids could be tried. 

PMID- 24566566
TI  - Hair loss in infancy.
AB  - Hair diseases represent a significant portion of cases seen by pediatric
      dermatologists although hair has always been a secondary aspect in pediatricians
      and dermatologists training, on the erroneous basis that there is not much
      information extractable from it. Dermatologists are in the enviable situation of
      being able to study many disorders with simple diagnostic techniques. The hair is
      easily accessible to examination but, paradoxically, this approach is often
      disregarded by non-dermatologist. This paper has been written on the purpose of
      trying to serve in the diagnostic process of daily practice, and trying to help,
      for example, to distinguish between certain acquired and some genetically
      determined hair diseases. We will focus on all the data that can be obtained from
      our patients' hair and try to help on using the messages given by hair for each
      patient. Quite often it is extremely hard to distinguish between abnormality and
      normality in neonatal hair aspects. We will specially focus in the most common
      physiological changes that may mislead to an incorrect diagnosis. Specific
      treatment for those hair diseases that do have one, and basic general approach to
      improve the cosmetic appearance of hair, will be also be discussed for those hair
      disturbances that do not have a specific treatment. 

PMID- 24566567
TI  - Hair loss in autoimmune systemic diseases.
AB  - Hair loss is commonly seen in autoimmune diseases. In pemphigus, although scalp
      involvement is common, hair loss is rarely reported. In classical bullous
      pemphigoid, alopecia is not reported while it is described in the Brusting-Perry
      variant of bullous pemphigoid and in epidermolysis bullosa acquisita. In these
      two diseases alopecia is cicatricial. In connective tissue diseases, in lupus
      erythematosus (LE) hair loss is frequent; in particular in LE there are two types
      of alopecia: non scarring and scarring alopecia. The non scarring form is a
      finding of acute systemic LE and the scarring form develops when a typical
      discoid lesion is located on the scalp. In dermatomyositis alopecia is usually
      non scarring and generalized. In scleroderma, alopecia is associated with en
      coupe de sabre morphea. 

PMID- 24566568
TI  - Trichoscopy: an update.
AB  - Hair and scalp disorders represent a substantial complaint in most
      dermatologists' daily practice. Trichoscopy is a simple and easy-to-perform
      technique that has been utilized for diagnosis and management of these patients.
      The interest for this technique had increased in the last years, and knowledge
      had expanded. This article reviews the most important dermoscopic patterns in
      normal Caucasian and African scalp, as well as in the most common trichological
      conditions. 

PMID- 24566569
TI  - Additional methods for diagnosing alopecia and appraising their severity.
AB  - The clinical diagnosis of hair diseases should be supported by objective
      techniques. In fact many methods are able to make advantage in some genetic
      syndromes with the aid of the microscope or to assess the severity of hair loss,
      or to distinguish a true disease from a visionary complaint of the patient. More
      commonly qualitative and quantitative methods are useful to distinguish
      androgenetic alopecia from telogen effluvium, or to recognize mild and initial
      cicatricial alopecias or the association of different forms of hair diseases. It
      is mandatory however the importance of the standardization of these technique in
      addition to identification of the normal values. Other techniques are essential
      to monitoring the effect of therapies for hair growth. Some of these methods are
      classified in non-invasive (pull test, wash test, daily count, phototrichogram),
      semi-invasive (trichogram and unit area trichogram) and invasive (biopsy). 

PMID- 24566570
TI  - Treatment for alopecia.
AB  - Satisfactory, evidence-based medicine regimen for treating alopecia are available
      in literature only regarding alopecia areata and androgenetic alopecia. About all
      the other kinds of alopecia, recommendations for therapy are still based upon the
      literature review, expert opinion, personal experience, expected adverse effects,
      and some pragmatic considerations such as the cost and the patient's compliance.
      Cicatricial alopecia is one of the most difficult challenges for dermatologists,
      because it is uncommon, its etiopathogenesis is not completely understood and
      there is no best therapy approach. Moreover, in Italy, most of the drugs
      mentioned below are not always available. Finally, therapies for hair disorders
      are long treatment and not always lead to a good improvement. 

PMID- 24566571
TI  - Topical use of phytotherapic cream (Capilen(r) cream) to prevent radiodermatitis
      in breast cancer: a prospective historically controlled clinical study.
AB  - AIM: The purpose of this study was to evaluate the ability of a topical
      phytotherapic product (Capilen(r) cream) to limit acute radiodermitis and delay
      the use of corticosteroids in patients with breast cancer (BC). METHODS: From
      January 2012 to August 2012, 30 consecutive patients, undergoing radiotherapy
      with adjuvant intent, were invited to use Capilen(r) cream two times daily two
      weeks before and during radiotherapy. An historical group was used as an external
      control. Acute skin toxicity was scored weekly according to RTOG/EORTC criteria.
      Time of occurrence of acute skin toxicity was taken as endpoint. RESULTS:
      Compliance was good. Overall, no significative statistical difference was
      observed in rate of acute radiation dermatitis, 46.7% in experimental arm versus
      63.3% in the historical control group, although only 3.3% of Capilen(r) cream
      treated patients had a G3 acute radiation dermatitis versus 10% of the control
      group. A delay in the onset of radition dermatitis in patients treated with
      Capilen(r) cream (P=0.04) was showed. CONCLUSION: Our findings suggested that
      Capilen(r) cream plays a role in reducing acute radiation dermatitis in breast
      cancer patients treated with adjuvant radiotherapy. Further evidence is needed to
      confirm these results.

PMID- 24566572
TI  - Dermo Beta Brachytherapy with 188Re in extramammary Paget's disease.
AB  - AIM: Extramammary Paget's disease (EMPD) is a rare neoplastic pathology involving
      the vulva, scrotum, and perianal areas, and it is characterized by a slow and
      insidious course. EMPD may also be associated with internal malignancy, and its
      clinical presentation features long-standing pruritic lesions, eczema-like,
      refractory to any therapy. The pathogenesis is unclear, and univocal
      standardization of treatment is yet to be determined. As regard to the patients
      who suffer from it, women are more often affected than men. The therapeutic
      approach depends on the extent of involvement; wide surgical excision is the
      first choice among treatments, but other forms of therapy, alone or in
      combination, include imiquimod 5%, photodynamic therapy, Mohs surgery as well as
      external beam radiotherapy and Brachytherapy. In the present paper a new
      therapeutic alternative is proposed: Dermo-Beta-Brachytherapy (DBBT) with 188Re.
      METHODS: Five patients with EMPD, one secondary and four primary cases, have been
      treated by Brachytherapy with DBBT. This therapy has been successfully used for
      non-melanocytic skin tumors and basically consists in the topical application of
      a specially designed, tailor-made mould containing a radioactive beta-emitting
      isotope, rhenium-188. RESULTS: The patients healed completely, after one session
      in one case and after two sessions in four cases, with 34 months mean follow-up.
      CONCLUSION: Brachyterapy could represent a new alternative therapy, instead than
      invasive treatments as surgery and conventional radiotherapy, capable to treat
      EMPD independently of its extension, with aesthetic and functional satisfactory
      results.

PMID- 24566573
TI  - Vitiligo, NB-UVB and tacrolimus: our experience in Naples.
AB  - AIM: The aim of the present study was to evaluate the efficacy and safety of
      narrowband UVB (NB-UVB) compared with tacrolimus ointment 0.1% in patients with
      bilateral vitiligo. METHODS: In this comparative study, four groups of patients
      were randomized. Each group was composed by 12 patients with bilateral vitiligo;
      in each group, every patient was irradiated with NB-UVB (length: 311 nm) twice a
      week for 9 months and applied tacrolimus ointment 0.1% twice a day on the other
      area in the same period. Before starting therapy and after 3, 6 and 9 months of
      therapy, a clinical and photographic evaluation of percentage of repigmentation
      was performed and Dermatology Life Quality Index Questionnaire was fulfilled.
      RESULTS: A repigmentation at least partial occurred in 71% of patients after 36
      weeks of treatment with tacrolimus ointment 0.1%; in the whole sample, 14
      patients (29%) showed no repigmentation at all, with 2 of them discontinuing the
      therapy because of side effects (erythema and folliculitis-like manifestations).
      A homogeneous repigmentation at least partial occurred in 69% of patients after
      36 weeks of treatment with NB-UVB; in the whole sample 15 patients (31%) showed
      no repigmentation at all, with 1 of them discontinuing the therapy because of
      side effects. CONCLUSION: The present study confirmed that the efficacy of NB-UVB
      phototherapy in vitiligo is comparable to tacrolimus ointment 0.1% therapy. On
      the basis of our study, we may suggest tacrolimus ointment 0.1% as an alternative
      to NB-UVB therapy for treating vitiligo.

PMID- 24566574
TI  - Costs of therapy with biologics in the treatment of moderate to severe plaque
      psoriasis in the context of the Italian health-care system.
AB  - AIM: Biologics were introduced as innovative and effective therapies for the
      treatment of moderate-to severe psoriasis. However, in the Italian context there
      are no comparative cost-effectiveness analyses of all biologics currently
      approved for psoriasis by the European Medicines Agency (EMA). This study
      estimates whether the cost of ustekinumab (meant as cost of drug therapies and
      monitoring) is lower, similar to or higher than that of anti-TNF-alpha. METHODS:
      The incremental cost-effectiveness ratio (ICER) and the cost-effectiveness ratio
      (CER) in terms of cost for patients achieving 75% improvement in PASI (PASI 75)
      were calculated. The analysis, both during the first 52 weeks, including
      induction and in maintenance period is based on efficacy data taken from single
      studies. The costs, based on official source, are calculated in the perspective
      of National Health Service (SSN). RESULTS: Ustekinumab has the lowest cost for
      responder, resulting always cost-effective and, in some case, cost saving in the
      baseline scenario at 52 weeks and in maintenance period. CONCLUSION: Ustekinumab
      seems to be the most favorable biologic in term of cost per PASI 75 responder for
      the treatment of psoriasis and it is cost-effective in all scenarios analyzed.
      Further cost-effectiveness evaluations based on data of use of long-term
      treatment with biologics in clinical practice, are necessary to support this
      results.

PMID- 24566575
TI  - Radiation therapy for recalcitrant pyoderma gangrenosum.
AB  - Pyoderma gangrenosum is a rare neutrophilic dermatosis, often associated with
      underlying systemic diseases. Treatment usually consists of topics and sometimes
      systemic immunosuppression. We present the case of a 32-year-old female patient
      undergoing radiation therapy for extensive recalcitrant pyoderma gangrenosum in
      which immunosuppressive measures were ineffective to control the disease.
      Treatment outcome was favourable with only mild side effects in the irradiated
      areas. Localized radiation therapy hence is a potential effective palliation for
      refractory cases of pyoderma gangrenosum, or patients unfit to undergo aggressive
      systemic immunosuppression. 

PMID- 24566576
TI  - Comparison of efficacy of 5% potassium hydroxide solution versus cryotherapy in
      the treatment of male genital wart: a randomized clinical trial.

PMID- 24566577
TI  - Penicillin as a therapeutic option in the treatment of in-hospital erysipelas.

PMID- 24566578
TI  - Prescription size and adherence in the management of psoriasis: is the more, the
      better?

PMID- 24566579
TI  - Acneiform eruption due to vitamin B12: a problem still unsolved.

PMID- 24566580
TI  - Pilar sheath acanthoma simulating basal cell carcinoma.

PMID- 24566581
TI  - A case of scrotal superficial basal cell carcinoma caused by chronic arsenic
      exposure.

PMID- 24566582
TI  - Kaposi's sarcoma induced by quinapril.

PMID- 24566583
TI  - Vitamin D status of schoolchildren in Northern Algeria, seasonal variations and
      determinants of vitamin D deficiency.
AB  - There are no published data on the vitamin D status of children living in North
      Africa. In 435 healthy Algerian children 5-15 years old, we found that vitamin D
      insufficiency (serum 25-hydroxyvitamin D (25OHD) <50 nmol/L) was frequent,
      especially in winter. Low vitamin D status was associated with increased
      parathyroid hormone (PTH) and leg deformation INTRODUCTION: As there are no
      published data on the vitamin D status of children living in North Africa, we
      evaluated the 25OHD concentration of healthy Algerian children at the end of
      summer and at the end of winter. As secondary objectives, we studied the various
      determinants of vitamin D status and the PTH-25OHD relationship in these
      subjects. METHODS: Four hundred thirty-five children 5-15 years old were examined
      and had a blood sample in September 2010. Of them, 408 were sampled again in
      March 2011. RESULTS: Median 25OHD concentration in the whole group was 71.4
      nmol/L in September and 52.9 nmol/L in March. In September, 58.4, 29.9, and 8.1%
      had a 25OHD concentration below 75, 50, and 30 nmol/L respectively. In March,
      these percentages increased to 65.2, 41.4, and 17.4% for the 75, 50, and 30
      nmol/L threshold, respectively. In multivariate analysis, older age, darker skin
      phototype, low daily vitamin D and calcium intake, poor socioeconomic status, and
      short daily sun exposure remained significantly associated with a 25OHD <50
      nmol/L at both visits. In 72 (16.6%) children, genu varum/valgum was present.
      Compared to the 363 children without leg deformation, they presented more
      frequently with the risk factors of vitamin D insufficiency. They also had lower
      25OHD concentrations and higher PTH and tALP. Serum PTH and 25OHD concentrations
      were negatively and significantly correlated (r = -0.43; p < 0.001) without a
      25OHD threshold above which PTH does not decrease anymore. CONCLUSION: Despite a
      sunny environment, vitamin D insufficiency is frequent in healthy Algerian
      children.

PMID- 24566584
TI  - Comparison of interactive voice response, patient mailing, and mailed registry to
      encourage screening for osteoporosis: a randomized controlled trial.
AB  - Guidelines recommend screening for osteoporosis with bone mineral density (BMD)
      testing in menopausal women, particularly those with additional risk factors for
      fracture. Many eligible women remain unscreened. This randomized study
      demonstrates that a single outreach interactive voice response phone call
      improves rates of BMD screening among high-risk women age 50-64. INTRODUCTION:
      Osteoporotic fractures are a major cause of disability and mortality. Guidelines
      recommend screening with BMD for menopausal women, particularly those with
      additional risk factors for fracture. However, many women remain unscreened. We
      examined whether telephonic interactive voice response (IVR) or patient mailing
      could increase rates of BMD testing in high risk, menopausal women. METHODS: We
      studied 4,685 women age 50-64 years within a not-for-profit health plan in the
      United States. All women had risk factors for developing osteoporosis and no
      prior BMD testing or treatment for osteoporosis. Patients were randomly allocated
      to usual care, usual care plus IVR, or usual care plus mailed educational
      materials. To avoid contamination, patients within a single primary care
      physician practice were randomized to receive the same intervention. The primary
      endpoint was BMD testing at 12 months. Secondary outcomes included BMD testing at
      6 months and medication use at 12 months. RESULTS: Mean age was 57 years.
      Baseline demographic and clinical characteristics were similar across the three
      study groups. In adjusted analyses, the incidence of BMD screening was 24.6% in
      the IVR group compared with 18.6% in the usual care group (P < 0.001). There was
      no difference between the patient mailing group and the usual care group (P =
      0.3). CONCLUSIONS: In this large community-based randomized trial of high risk,
      menopausal women age 50-64, IVR, but not patient mailing, improved rates of BMD
      screening. IVR remains a viable strategy to incorporate in population screening
      interventions.

PMID- 24566585
TI  - Additive effects of antiresorptive agents and exercise on lumbar spine bone
      mineral density in adults with low bone mass: a meta-analysis.
AB  - INTRODUCTION: Exercise has been recommended to increase bone mass and prevent
      osteoporosis. While current treatment of osteoporosis mainly involves the use of
      antiresorptive agents, it is unclear whether there are any additive effects in
      improving bone mass when antiresorptive agents and exercise are jointly used.
      METHODS: A structured and comprehensive search of databases was undertaken along
      with hand searching of key journals and reference lists. The combined
      interventions of antiresorptive agents and exercise were examined for their
      additive effects on lumbar spine bone mineral density (BMD) among adults with low
      bone mass. Trial quality was assessed using the Jadad quality score. Study
      outcomes for analysis, absolute change (grams per square centimeter) or relative
      change (in percent) in BMD, at the lumbar spine were compared by calculating
      standardized mean difference (SMD) using fixed and random effect models. RESULTS:
      Seven randomized controlled trials (RCT) met the predetermined inclusion
      criteria. The increase in lumbar spine BMD of the combined-intervention group was
      significantly greater than that of the antiresorptive agent-alone group (fixed
      effect model: SMD = 0.55; 95% confidence interval (CI) = 0.36, 0.75; overall
      effect Z-value = 5.51; p < 0.00001). Subgroup analyses also showed consistent
      results. Methodological quality of most included studies was scored 3 by the
      Jadad criterion, and publication bias was slight according to funnel plots.
      CONCLUSION: It was found that combining antiresorptive agents with exercise had
      additive effects on improving lumbar spine bone mass gains in adults with low
      bone mass. To verify the additive effects further, more RCTs with longer duration
      and larger sample sizes are needed.

PMID- 24566586
TI  - Alendronate, a bisphosphonate, increased upper and lower gastrointestinal
      bleeding: risk factor analysis from a nationwide population-based study.
AB  - Patients receiving alendronate for osteoporosis carry a significantly higher risk
      of developing upper gastrointestinal bleeding (GIB) and lower GIB (hazard ratio
      1.32 and 1.84, respectively) after adjusting for potential confounding factors
      such as age, gender, co-morbidity, and some medications. The risk factors
      associated with GIB were further analyzed. INTRODUCTION: Patients receiving
      alendronate, a type of bisphosphonate, for osteoporosis have a higher risk of
      developing upper gastrointestinal bleeding (UGIB). Whether patients receiving
      alendronate also have a higher risk of lower gastrointestinal bleeding (LGIB) has
      not been studied. In this study, we investigated the association between GIB and
      alendronate use and to identify the possible risk factors of GIB among
      alendronate users. METHODS: Using the National Health Insurance (NHI) Research
      Database of Taiwan, 3,000 alendronate users and 12,000 age-, sex-, and enrollment
      time-matched controls were extracted for analysis from a cohort data set of
      1,000,000 randomly sampled subjects. Cox proportional hazard regression models
      were used to identify the risk factors for UGIB and LGIB in all enrollees and
      alendronate users after adjustments for age, gender, comorbidity (hypertension,
      diabetes mellitus, coronary heart disease, heart failure, chronic renal disease,
      chronic obstructive pulmonary disease, peptic ulcer, and cirrhosis), and
      medications (nonsteroidal anti-inflammatory drugs [NSAIDs], aspirin, steroids,
      clopidogrel, ticlopidine, warfarin, and selective serotonin reuptake inhibitors).
      RESULTS: During a median of 1.30-year follow-up, patients receiving alendronate
      had significant higher risk of UGIB and LGIB after adjusting for age, gender, and
      potential confounding factors such as comorbidity and medications. Age, chronic
      renal disease, NSAID, and clopidogrel use may be independent risk factors for
      UGIB among alendronate users. Age, male gender, clopidogrel, and ticlopidine use
      may be independent risk factors for LGIB among alendronate users. CONCLUSION:
      Patients receiving alendronates seemed to carry a higher risk for UGIB and LGIB,
      respectively, after adjustment for age, sex, underlying comorbidity, and certain
      medications.

PMID- 24566587
TI  - Antidepressant use and 10-year incident fracture risk: the population-based
      Canadian Multicentre Osteoporosis Study (CaMoS).
AB  - We used data from a large, prospective Canadian cohort to assess the association
      between selective serotonin reuptake inhibitors (SSRIs) and serotonin and
      noradrenaline reuptake inhibitors (SNRIs) and fracture. We found an increased
      risk of fractures in individuals who used SSRI or SNRI, even after controlling
      for multiple risk factors. INTRODUCTION: Previous studies have suggested an
      association between SSRIs and increasing risk of fragility fractures. However,
      the majority of these studies were not long-term analyses or were performed using
      administrative data and, thus, could not fully control for potential confounders.
      We sought to determine whether the use of SSRIs and SNRIs is associated with
      increased risk of fragility fracture, in adults aged 50 + . METHODS: We used data
      from the Canadian Multicentre Osteoporosis Study (CaMos), a prospective randomly
      selected population-based community cohort; our analyses focused on subjects aged
      50+. Time to event methodology was used to assess the association between
      SSRI/SNRI use, modeled time-dependently, and fragility fracture. RESULTS: Among
      6,645 subjects, 192 (2.9%) were using SSRIs or/and SNRIs at baseline. During the
      10-year study period, 978 (14.7%) participants experienced at least one fragility
      fracture. In our main analysis, SSRI/SNRI use was associated with increased risk
      of fragility fracture (hazard ratio (HR), 1.88; 95% confidence intervals (CI),
      1.48-2.39). After controlling for multiple risk factors, including Charlson
      score, previous falls, and bone mineral density hip and lumbar bone density, the
      adjusted HR for current SSRI/SNRI use remained elevated (HR, 1.68; 95% CI, 1.32
      2.14). CONCLUSIONS: Our results lend additional support to an association between
      SSRI/SNRI use and fragility fractures. Given the high prevalence of
      antidepressants use, and the impact of fractures on health, our findings may have
      a significant clinical impact.

PMID- 24566588
TI  - Accuracy of trabecular structure by HR-pQCT compared to gold standard MUCT in the
      radius and tibia of patients with osteoporosis and long-term bisphosphonate
      therapy.
AB  - Despite an increasing use of high-resolution peripheral quantitative computed
      tomography (HR-pQCT) to evaluate bone morphology in vivo, there are reservations
      about its applicability in patients with osteoporosis and antiresorptive therapy.
      This study shows that HR-pQCT provides acceptable in vivo accuracy for bone
      volume fraction (BV/TV) in patients with osteoporosis and bisphosphonate (BP)
      treatment. INTRODUCTION: The primary aim was to analyze agreement of trabecular
      structure between HR-pQCT and gold standard microtomography (MUCT) in patients
      with osteoporosis and long-term BP therapy. METHODS: In the BioAsset study, we
      analyzed cadaver radii and tibiae of 34 postmenopausal females (81.1 +/- 7.1
      years) with osteoporosis (no BP n = 22, 1-5 years BP n = 5, >5 years BP n = 7).
      Two HR-pQCT protocols (patient-mode and MUCT-mode) were compared with gold
      standard MUCT after image registration. Undecalcified histological sections were
      obtained to quantify nonmineralized bone matrix. Bland-Altman plots illustrated
      methodological agreement. Multiple regression analysis was used to test for
      variables associated with method agreement. RESULTS: In the radius and tibia,
      patient-mode HR-pQCT derived indices including bone volume fraction, trabecular
      number, and trabecular separation correlated well with gold standard MUCT (R(2) =
      0.78 - 0.88) except for trabecular thickness (R(2) = 0.11). Bland-Altman plots
      illustrated adequate agreement for bone volume fraction. Lower agreement of
      trabecular number and trabecular separation improved with decreasing structural
      impairment at the tibia only. Trabecular thickness was not appropriately assessed
      with HR-pQCT at both skeletal sites. Higher agreement for bone volume fraction
      was associated with increasing tissue mineral density in the tibia. CONCLUSIONS:
      HR-pQCT provides acceptable in vivo accuracy for BV/TV in patients with
      osteoporosis and BP treatment. Higher TMD was associated with higher BV/TV
      accuracy in vivo. Overall, methodological agreement got less accurate with
      increasing structural impairment in the tibia.

PMID- 24566590
TI  - Lower heart rate in the early postoperative period does not correlate with long
      term outcomes after repair of type A acute aortic dissection.
AB  - Little evidence exists regarding the need for a reduction in postoperative heart
      rate after repair of type A acute aortic dissection. This single-center
      retrospective study was conducted to determine if lower heart rate during the
      early postoperative phase is associated with improved long-term outcomes after
      surgery for patients with type A acute aortic dissection. We reviewed 434
      patients who underwent aortic repair between 1990 and 2011. Based on the average
      heart rate on postoperative days 1, 3, 5, and 7, 434 patients were divided into
      four groups, less than 70, 70-79, 80-89, and greater than 90 beats per minute.
      The mean age was 63.3 +/- 12.1 years. During a median follow-up of 52 months
      (range 16-102), 10-year survival in all groups was 67%, and the 10-year aortic
      event-free rate was 79%. The probability of survival and being aortic event-free
      using Kaplan-Meier estimates reveal that there is no significant difference when
      stratified by heart rate. Cox proportional regression analysis for 10-year
      mortality shows that significant predictors of mortality are age [Hazard Ratio
      (HR) 1.04; 95% confidence interval (CI) 1.07-1.06; p = 0.001] and perioperative
      stroke (HR 2.30; 95% CI 1.18-4.50; p = 0.024). Neither stratified heart rate
      around the time of surgery nor beta-blocker use at the time of discharge was
      significant. There is no association between stratified heart rate in the
      perioperative period with long-term outcomes after repair of type A acute aortic
      dissection. These findings need clarification with further clinical trials.

PMID- 24566591
TI  - Summary of clinical practice guidelines for acute kidney injury.
AB  - Clinical practice guidelines are intended to standardize the diagnosis and
      treatment of diseases in order to improve both patient outcomes and resource
      utilization, using evidence-based criteria. As recently as a decade ago, there
      was no agreed upon definition of acute kidney injury (AKI), making it difficult
      to conduct proper clinical studies on the epidemiology and treatment of the
      disorder. Following the advent of the Risk, Injury, Failure, Loss, and End-stage
      (RIFLE) criteria for defining AKI, several guidelines for the diagnosis and
      management of AKI have been developed. In our review, we present a narrative
      description and comparison of the major published guidelines. Overall, there has
      been significant agreement among the various guidelines, and each seems well
      reasoned and clinically useful. Perhaps the most striking conclusion upon review
      of the various guidelines is the limited scope of knowledge about optimal
      management of patients with AKI. 

PMID- 24566589
TI  - Prognostic impact of regional arterial stiffness in hypertensive patients.
AB  - Many reports have shown that brachial-ankle pulse wave velocity (baPWV) and
      carotid-femoral PWV are prognostic factors for cardiovascular diseases. We
      evaluated heart-carotid PWV, heart-femoral PWV (hfPWV), and femoral-ankle PWV
      (faPWV) using carotid and femoral sensors. Our objectives were to reveal
      correlations among PWVs and to determine the clinical importance of the
      respective PWVs in predicting the cardiovascular events. This prospective cohort
      study included 338 patients with essential hypertension (mean age 61.3 +/- 0.7,
      mean follow-up period 6.5 +/- 0.1 years) whose regional PWVs were measured.
      Primary end points were stroke, cardiovascular diseases (CVD), and death. Kaplan
      Meier analysis showed that subjects with higher faPWV and baPWV had a
      significantly higher incidence of stroke (p = 0.0288 and 0.0277, respectively),
      subjects with higher hfPWV had a significantly higher incidence of CVD (p =
      0.0212), subjects with higher baPWV and hfPWV had a significantly higher
      incidence of stroke + CVD (p = 0.0070 and 0.0463, respectively), and subjects
      with higher baPWV had a significantly higher mortality rate (p = 0.0367). Cox
      proportional hazard model revealed that baPWV was a significant risk factor for
      stroke + CVD after adjustment for traditional risk factors (relative risk: 14.50,
      p = 0.0288). Higher baPWV may be a risk factor for stroke and CVD, but the
      prognostic impact of regional PWVs is still unclear in patients with
      hypertension. 

PMID- 24566592
TI  - Canadian health care institution resource utilization resulting from skeletal
      related events.
AB  - PURPOSE: We describe the types of major institution health care resources
      consumed as a result of skeletal-related events (SREs) [ie, pathological
      fracture, bone surgery, radiation to bone, spinal cord compression]. METHODS: A
      retrospective multicenter chart review of cancer patients with bone metastases
      who experienced SREs was conducted. Patients with multiple SREs occurring during
      the same hospitalization within 21 days of each other were grouped into SRE
      clusters. RESULTS: We reviewed 156 patient charts from 4 Canadian institutions,
      accounting for 358 SREs and 259 SRE clusters. Of the total patients, 63%
      experienced 1 SRE; 19%, 2 SREs; 10%, 3 SREs; and 8%, >= 4 events. Health care
      resource utilization was captured for >= 90 days following each SRE: 54% of all
      SRE events resulted in an inpatient stay; 34% in an emergency visit; 85% of SREs
      required the use of diagnostic procedures (including radiography, magnetic
      resonance imaging, Computerized Axial Tomography scans, and radio scans); 57%
      required radiation treatment; 34% required a surgical procedure; 35% received
      outpatient treatment visits (ie, physiotherapy or occupational therapy). Bone
      surgery and spinal cord compression were more often associated with
      hospitalization than were other SRE types. Spinal cord compression was associated
      with the greatest number of inpatients stays (1.09 per SRE), longest duration of
      hospital stay (mean 26.18 days per SRE), and more outpatient visits, relative to
      other SRE types. CONCLUSION: Results of our Canadian retrospective study clearly
      demonstrate that SREs occur in cancer patients and each SRE is associated with
      considerable institutional consumption of health care resources.

PMID- 24566593
TI  - Clinical pearls in perioperative medicine.
AB  - At the 2001 annual meeting of the American College of Physicians (ACP), a new and
      innovative teaching format, the "Clinical Pearls" session, was introduced.
      Clinical Pearls sessions were designed to teach physicians using clinical cases.
      The session format involves specialty speakers presenting a number of short cases
      to a physician audience. Each case is followed by a multiple-choice question,
      answered by each attendee using an electronic audience-response system. After a
      summary of the answer distribution is shown, the correct answer is displayed and
      the speaker discusses important teaching points and clarifies why one answer is
      most clinically appropriate. Each case presentation ends with 1 or 2 "Clinical
      Pearls," defined as a practical teaching point, supported by the literature, and
      generally not well known to most internists. The Clinical Pearls sessions are
      consistently one the most popular and well attended sessions at the American
      College of Physicians' national meeting each year. Herein, we present the
      Clinical Pearls in Perioperative Medicine, presented at the ACP National Meeting
      in San Francisco, California, April 11-13, 2013. 

PMID- 24566594
TI  - The Massachusetts General Hospital Pulmonary Embolism Response Team (MGH PERT):
      creation of a multidisciplinary program to improve care of patients with massive
      and submassive pulmonary embolism.
AB  - New and innovative tools have emerged for the treatment of massive and submassive
      pulmonary embolism (PE). These novel treatments, when considered alongside
      existing therapy, such as anticoagulation, systemic intravenous thrombolysis, and
      open surgical pulmonary embolectomy, have the potential to improve patient
      outcomes. However, data comparing different treatment modalities are sparse, and
      guidelines provide only general advice for their use. Treatment decisions rest on
      clinician expertise and institutional resources. Because various medical and
      surgical specialties offer different perspectives and expertise, a
      multidisciplinary approach to patients with massive and submassive PE is
      required. To address this need, we created a novel multidisciplinary program -
      the Massachusetts General Hospital (MGH) Pulmonary Embolism Response Team (PERT) 
      which brings together multiple specialists to rapidly evaluate intermediate- and
      high-risk patients with PE, formulate a treatment plan, and mobilize the
      necessary resources to provide the highest level of care. Development of a
      clinical, educational, and research infrastructure, as well as the creation of a
      national PERT consortium, will make our experience available to other
      institutions and serve as a platform for future studies to improve the care of
      complex patients with massive and submassive PE. 

PMID- 24566595
TI  - Perioperative management of target-specific oral anticoagulants.
AB  - Target-specific oral anticoagulants (TSOACs), which offer rapid onset and more
      predictable pharmacokinetics/dynamics compared with vitamin K antagonists, are
      rapidly growing in number and approved indications. At least 1 in 10 Americans
      receiving outpatient anticoagulant therapy requires interruption of
      anticoagulation for an invasive procedure annually, and management of these new
      agents in the perioperative setting is made challenging by difficulty measuring
      anticoagulant effect and the lack of effective reversal. Surgical planning must
      account for individual patient risks for bleeding and thrombosis, the type of
      procedure, and expected drug clearance. Based upon these considerations, a
      perioperative plan encompassing timing of TSOAC cessation and resumption, as well
      as bridging therapy, if needed, can be developed. Perioperative strategies remain
      largely predicated on extrapolations from pharmacokinetics and expert opinion,
      though a growing body of literature is providing greater guidance in this
      important area. 

PMID- 24566596
TI  - Transitional care clinic for uninsured and medicaid-covered patients with
      diabetes mellitus discharged from the hospital: a pilot quality improvement
      study.
AB  - Transitioning from the inpatient to outpatient setting is often a problematic
      aspect of diabetes mellitus (DM) care. Different factors during hospitalization
      may adversely affect glycemic control in patients, who are frequently discharged
      on regimens that differ markedly from prehospitalization outpatient regimens.
      Moreover, the discharge recommendations may not have been tested adequately
      during a relatively short hospital length of stay and pose a significant threat
      to patient safety upon discharge. Our pilot study evaluated the effect on
      hospital utilization of the transitional care clinic (TCC), where patients with
      DM are seen within 2 to 5 days of hospital discharge. One hundred patients with
      DM, who were either medically indigent (no insurance or Medicaid and no primary
      care providers) or covered by Medicaid, and who did not have a primary care
      provider, were randomized into either a control or an intervention group upon
      discharge from the hospital. Subjects from the intervention group (n = 50) were
      seen in the TCC. All subjects were contacted 90 days after discharge to collect
      information about emergency department visits and readmissions. Thirteen subjects
      from the control group and 13 from the intervention group visited the emergency
      department within 90 days of discharge. Fourteen control subjects (28%) and 10
      intervention patients (20%) were rehospitalized for various medical conditions
      during the follow-up period (P = not significant). Among patients originally
      admitted for DM-related issues, 6 of 14 in the control group (42.9%) and 2 out of
      16 in the intervention group (12.5%) were readmitted during follow-up (P < 0.05).
      We conclude that the TCC may be effective for the prevention of
      rehospitalizations in indigent patients admitted for DM-related problems and who
      did not have primary care providers. The benefit of the TCC was not seen when
      patients with DM were admitted for other medical problems. Larger randomized
      controlled trials are needed to confirm this preliminary finding. 

PMID- 24566597
TI  - A systematic approach to the preoperative medical evaluation of adults.
AB  - The number, age, and medical complexity of patients undergoing elective
      noncardiac surgery is rising worldwide. Internists, family physicians, and
      midlevel providers asked to perform preoperative medical evaluations. However,
      lack of consensus has led to wide variation in practice in what is included and
      addressed in these evaluations, and the efficacy of these assessments has been
      debated. The intended purpose of the evaluation seems to be universally accepted
      as aiming to assess and identify risks associated with the patient's comorbid
      medical conditions and the specific surgical procedure. The goal is to minimize
      those risks. Herein, we propose a systematic approach to the preoperative medical
      evaluation based on the best available evidence and expert opinion, with an
      emphasis on identifying all potentially pertinent patient- and surgery-specific
      risk factors. 

PMID- 24566598
TI  - New health care measures: emphasis on better management of postsurgical pain and
      postoperative nausea and vomiting.
AB  - Value-based purchasing and the Hospital Consumer Assessment of Healthcare
      Providers and Systems are tying patient-centric measures to reimbursements.
      Hospitals should be particularly concerned about management of postoperative pain
      and control of postoperative nausea and vomiting (PONV), known to adversely
      impact overall patient satisfaction. Anesthesiologists are likely to be on the
      frontlines of these transitions. Although postoperative pain is not always
      effectively managed, clinicians have the pharmacological tools and guidelines for
      better pain control. Considerable work has been done in PONV to better identify
      high-risk patients and effective prophylactic agents. Postoperative pain control
      and preventing PONV are two relatively straightforward ways to respond to new
      quality metrics. The aim of this review is to raise practitioner awareness of
      these new quality metrics and provide an overview of the current tools and
      methods used to improve postoperative pain control and PONV. 

PMID- 24566599
TI  - Efficacy of ceftaroline fosamil for bacteremia associated with community-acquired
      bacterial pneumonia.
AB  - OBJECTIVES: Few publications of prospective studies have described patient
      outcomes in community-acquired bacterial pneumonia (CABP)-associated bacteremia.
      Our objective, in performing this subgroup analysis, was to assess outcomes in
      subjects with CABP-associated bacteremia in 2 randomized, double-blind clinical
      studies comparing treatment with ceftaroline fosamil versus ceftriaxone. METHODS:
      Our analysis summarizes baseline subject demographics, distribution of baseline
      pathogens isolated from blood cultures, clinical response rates at Day 4, and
      clinical cure rates at end of therapy and test of cure (8 to 15 days after end of
      therapy) in subjects with bacteremic CABP in the ceFtarOline Community-acquired
      pneUmonia trial vS ceftriaxone in hospitalized patients (FOCUS) studies. RESULTS:
      In the FOCUS studies, 23 of 614 patients in the ceftaroline fosamil-treated group
      and 22 of 614 patients in the ceftriaxone-treated group had CABP-associated
      bacteremia. Baseline demographics were similar between groups. Streptococcus
      pneumoniae was the most common baseline bloodstream isolate. For subjects with
      CABP-associated bacteremia, clinical response/cure rates were similar at Day 4
      (60.9% vs 59.1%), end of therapy (69.6% vs 72.7%), and test of cure (69.6% vs
      68.2%) for ceftaroline fosamil and ceftriaxone, respectively. CONCLUSIONS: In
      subjects with CABP-associated bacteremia, ceftaroline fosamil demonstrated
      similar clinical outcomes at Day 4, end of therapy, and test of cure compared
      with ceftriaxone.

PMID- 24566600
TI  - Chronic obstructive pulmonary disease: clinical review and update on consensus
      guidelines.
AB  - In the last 2 decades, chronic obstructive pulmonary disease (COPD) has been
      increasingly recognized as a major public health problem. Since the introduction
      of the Global Initiative for Chronic Obstructive Lung Disease in 1998, growing
      interest in the pathogenesis and management of patients with COPD has led to
      notable improvements in patient care and quality of life. Despite greater
      awareness of this common preventable disease and major therapeutic advances
      during this period, the global impact of COPD remains strikingly large. We
      provide an evidence-based clinical review on COPD, with a focus on internists as
      the target audience. 

PMID- 24566601
TI  - Prevention of cardiovascular disease: updating the immensity of the challenge and
      the role of risk factors.
AB  - Despite remarkable decreases in the mortality of coronary heart disease, there is
      concern that continued high levels of cardiovascular risk in the population may
      reverse these gains. By 2015, the prevalence of cardiovascular disease in the
      United States will be 37.8%. Obesity, hypertension, dyslipidemia, diabetes
      mellitus (DM), metabolic syndrome, and inflammation are the primary components
      driving cardiovascular risk. Approximately 70% of adults are overweight or obese,
      yet diet quality continues to deteriorate and authoritative information is
      insufficiently promoted. More than half of US adults have lipid abnormalities;
      27% of US adults have high values of low-density lipoprotein cholesterol, 23%
      have low values of high-density lipoprotein cholesterol concentrations, and 30%
      have high triglyceride levels. Approximately 34% of adults have hypertension; 40%
      of these adults are unaware of the diagnosis. In patients with hypertension who
      are treated, 54% remain uncontrolled. The prevalence of hypertension in elderly
      patients has increased from 35% to 41%. In addition, 30% of adults have
      prehypertension. The burden of hypertension alone accounts for approximately 1000
      deaths per day. Trends in the prevalence of glucose intolerance are similar. The
      prevalence of DM is approximately 12%, with 27% of cases remaining undiagnosed.
      Thirty-five percent of US adults aged > 20 years have prediabetes and 7.3% of
      adults are unaware of the diagnosis. If the present trends continue, 1 in 3 of US
      adults will have DM by 2050. Participation in exercise has been low and a
      "straight line" for > 2 decades. Accelerometer data indicate that individuals who
      attain minimal exercise goals are only a fraction of the often quoted levels of >
      35%. Control of risk factors in primary prevention, although improved, remains
      decidedly incomplete. Lowering the burden of cardiovascular risk factors at the
      population level has been exceptionally difficult. For reasons outlined, the
      solution to this problem is multifaceted and extends well beyond the delivery of
      medical care into the structure of society and the environment. 

PMID- 24566602
TI  - Impact of a pharmacy-based glucose management program on glycemic control in an
      inpatient general medicine population.
AB  - OBJECTIVE: A pharmacy-based glucose management program was evaluated to determine
      whether improved glycemic control could be achieved in an inpatient general
      medicine patient population. METHODS: A retrospective chart review of 151
      patients with blood glucose (BG) values outside the range of 70 to 180 mg/dL
      within a 24-hour period was conducted. Observations for the baseline group with
      no pharmacy program in place were collected from admissions during July 2010 and
      for the intervention group in October 2010. The primary goal of the study was to
      determine if the pharmacy program improved patient days within the BG range of 70
      to 250 mg/dL. The odds of poor glycemic control for patients in the intervention
      versus baseline groups were assessed by multivariate generalized estimating
      equations. These methods were also used to assess patient characteristics
      associated with poor glycemic control. RESULTS: No evidence was observed that the
      pharmacy program decreased the number of days spent out of the targeted blood
      glucose range (70-250 mg/dL; odds ratio, 1.08; 95% CI, 0.88-1.24). However, the
      subgroup of patients whose admission BG was < 200 mg/dL (49% of the intervention
      group) experienced a significant reduction in days spent out of the BG range (70
      250 mg/dL; odds ratio, 0.42; 95% CI, 0.22-0.82). No improvement in glycemic
      control was observed in patients with an admission BG >= 200 mg/dL; these
      patients had more disease- and social-related factors associated with poor
      glycemic control. CONCLUSION: The primary finding of this analysis was that there
      was no global benefit of the pharmacy-based glucose management program for
      improving BG values compared with usual care. Patients whose admission glucose
      was < 200 mg/dL experienced improvement in glycemic control in the pharmacy-based
      program. Maintaining the BG level of the remaining patients was generally more
      complicated from a disease-state and social perspective and patients experienced
      no improvement. These patients may require a more intense, multidisciplinary
      approach that is better matched to the constellation of factors responsible for
      their condition.

PMID- 24566603
TI  - Korean Youth Risk Behavior Surveillance Survey: Association Between Part-time
      Employment and Suicide Attempts.
AB  - This study investigated the association between in-school students' part-time
      work and 1-year suicide attempts in Korea. The authors analyzed Korean Youth Risk
      Behavior Surveillance data (2008), which included 75 238 samples that represent
      Korean middle and high school students. Multiple logistic regression analysis was
      performed to investigate the association between part-time work and suicide
      attempt during the past 1 year, controlled by sociodemographic, school-related,
      lifestyle, and psychological factors. Among high school students, there was no
      association between part-time work and suicide attempts. However, part-time work
      was associated with suicide attempts significantly among middle school students
      (odds ratio = 1.59; 95% confidence interval = 1.37-1.83). Despite the limitation
      that details of the part-time work were not included in this study, it was found
      that middle school students' part-time work may increase suicide attempts, and
      the circumstances of Korean adolescents' employment, especially that of younger
      adolescents, would need to be reconsidered to prevent their suicide attempts. 

PMID- 24566604
TI  - The relationship between healthy lifestyle and hospital utilization among adults
      with diabetes: results from a national cohort in Taiwan.
AB  - The aim of this study was to investigate whether adopting healthy lifestyle
      habits, such as engaging in leisure time physical activity (LTPA), adopting
      recommended dietary patterns, and not smoking, are associated with reduced
      hospitalizations over 1 year among adults with diabetes. We analyzed data from a
      national sample of people aged 18 years and above with self-reported physician
      diagnosed diabetes (n = 664) through linkage to the 2001 National Health
      Interview Survey in Taiwan and the 2002 National Health Insurance claims data.
      Multivariate analysis showed that participants reporting greater than 150 min/wk
      of moderate-intensity activity had a significantly lower chance for
      hospitalization (odds ratio = 0.52; 95% confidence interval [CI] = 0.27-0.98),
      fewer admissions (incidence rate ratio [IRR] = 0.58; 95% CI = 0.33-1.00), and
      fewer hospital bed days (IRR = 0.42; 95% CI = 0.20-0.92) compared with inactive
      individuals. Diet control and smoking status did not significantly predict
      hospital use after controlling for other factors. Our findings indicate that
      increased LTPA results in reduced hospitalization among adults with diabetes. 

PMID- 24566605
TI  - Utilization of the Local Government Health Insurance Scheme (JKA) for Maternal
      Health Services Among Women Living in Underdeveloped Areas of Aceh Province,
      Indonesia.
AB  - Aceh province of Indonesia created its own health coverage scheme called Jaminan
      Kesehatan Aceh (JKA) to cover Aceh's populations who were not registered under
      insurance for the poor (Jamkesmas). This study aims to compare the utilization
      rate of maternal health care (MHC) services and contraceptive prevalence rate
      (CPR) before JKA, during the transition period, and after JKA had been
      established. A cross-sectional household survey was conducted from June 2011 to
      July 2012. Utilization of MHC services and CPR during the 3 periods was assessed
      using a questionnaire. The Mantel-Haenszel chi(2) test was used to examine the
      association between period and coverage. Generalized estimating equations (GEEs)
      were used to examine utilization and type of service, period of service, and type
      of scheme. Coverage of utilization of skilled birth attendants significantly
      improved among the JKA holders (odds ratio = 1.84; 95% confidence interval = 1.18
      2.89). JKA, thus, has shown its positive impact. 

PMID- 24566606
TI  - HPV16E7 silencing enhances susceptibility of CaSki cells to natural killer cells.
AB  - The aim of the present study was to investigate the cytotoxicity of natural
      killer (NK) cells to CaSki cells following knockdown of the E7 protein of the
      human papillomavirus type 16 (HPV16E7). Recombinant adenovirus-short hairpin-E7
      protein of the human panillomavirus type 16 (Ad-sh-HPV16E7) was constructed and
      used to infect CaSki cells. The expression of HPV16E7 in CaSki cells was assessed
      using western blot analysis. The expression of cell surface molecule major
      histocompatibility complex-I (MHC-I) in CaSki cells infected with Ad-sh-HPV16E7
      was examined using flow cytometry. The cytotoxicity of NK cells isolated and
      expanded from healthy volunteers on Ad-sh-HPV16E7-infected CaSki cells was
      assessed using the lactate dehydrogenase (LDH) release assay. Ad-sh-HPV16E7 was
      successfully constructed and able to inhibit HPV16E7 the expression in CaSki
      cells. The expression of major histocompa-tibility complex I (MHC-I), a surface
      molecule, in CaSki cells was increased after infection with Ad-sh-HPV16E7.
      Compared with the controls, the cytotoxicity of NK cells on CaSki cells, which
      were infected with Ad-sh-HPV16E7, was decreased (p<0.05). In conclusion, HPV16E7
      suppresses the expression of MHC-I on CaSki cells to evade cytotoxic T-cell (CTL)
      response. However, it was possible to enhance the cytotoxicity of expanded NK
      cells to cervical cancer cells or HPV16-infected cells in vitro, indicating that
      NK cells may be used for immunotherapy of cervical cancer.

PMID- 24566607
TI  - Differences among estimates of critical power and anaerobic work capacity derived
      from five mathematical models and the three-minute all-out test.
AB  - Estimates of critical power (CP) and anaerobic work capacity (AWC) from the power
      output vs. time relationship have been derived from various mathematical models.
      The purpose of this study was to examine estimates of CP and AWC from the
      multiple work bout, 2- and 3-parameter models, and those from the 3-minute all
      out CP (CP3min) test. Nine college-aged subjects performed a maximal incremental
      test to determine the peak oxygen consumption rate and the gas exchange
      threshold. On separate days, each subject completed 4 randomly ordered constant
      power output rides to exhaustion to estimate CP and AWC from 5 regression models
      (2 linear, 2 nonlinear, and 1 exponential). During the final visit, CP and AWC
      were estimated from the CP3min test. The nonlinear 3-parameter (Nonlinear-3)
      model produced the lowest estimate of CP. The exponential (EXP) model and the
      CP3min test were not statistically different and produced the highest estimates
      of CP. Critical power estimated from the Nonlinear-3 model was 14% less than
      those from the EXP model and the CP3min test and 4-6% less than those from the
      linear models. Furthermore, the Nonlinear-3 and nonlinear 2-parameter (Nonlinear
      2) models produced significantly greater estimates of AWC than did the linear
      models and CP3min. The current findings suggested that the Nonlinear-3 model may
      provide estimates of CP and AWC that more accurately reflect the asymptote of the
      power output vs. time relationship, the demarcation of the heavy and severe
      exercise intensity domains, and anaerobic capabilities than will the linear
      models and CP3min test.

PMID- 24566608
TI  - Firefighter health and fitness assessment: a call to action.
AB  - Sudden cardiac deaths experienced by firefighters in the line of duty account for
      the largest proportion of deaths annually. Several fire service standards for
      fitness and wellness have been recommended but currently only 30% of U.S. fire
      departments are implementing programs for this purpose. The Department of
      Homeland Security Science and Technology Directorate has initiated the
      Physiological Health Assessment System for Emergency Responders (PHASER) program
      aiming to reduce these line-of-duty deaths through an integration of medical
      science and sensor technologies. Confirming previous reports, PHASER
      comprehensive risk assessment has identified lack of physical fitness with
      propensity for overexertion as a major modifiable risk factor. We sought to
      determine if current levels of fitness and cardiovascular disease (CVD) risk
      factors in a contemporary cohort of firefighters were better than those reported
      over the past 30 years. Fifty-one firefighters from a Southern California
      department were characterized for physical fitness and CVD risk factors using
      standard measures. Overall, physical fitness and risk factors were not different
      from previous reports of firefighter fitness and most subjects did not achieve
      recommended fitness standards. Considering the lack of widespread implementation
      of wellness/fitness programs in the U.S. fire service together with our findings
      that low physical fitness and the presence of CVD risk factors persist, we issue
      a call to action among health and fitness professionals to assist the fire
      service in implementing programs for firefighters that improve fitness and reduce
      CVD risk factors. Fitness professionals should be empowered to work with fire
      departments lending their expertise to guide programs that achieve these
      objectives, which may then lead to reduced incidence of sudden cardiac death or
      stroke.

PMID- 24566610
TI  - How much do soldiers know about the morphine they carry on operations? A
      questionnaire study of knowledge and understanding of the morphine auto-injector
      on Op HERRICK 17.
AB  - INTRODUCTION: Morphine auto-injectors are issued to all British soldiers on
      operations in Afghanistan who deploy forward of Camp Bastion, the main British
      base. Previous studies have reviewed the effectiveness of various pre-hospital
      analgesics, but there is no record of the knowledge and confidence of the
      relatively medically untrained soldiers who carry and use intramuscular morphine
      on the battlefield. The aim of this study was to assess soldiers' knowledge and
      confidence of the morphine auto-injector with a view to guiding further training.
      METHODS: Structured questionnaire distributed to soldiers in two patrol bases in
      Helmand Province during Op HERRICK 17. RESULTS: 232 questionnaires were completed
      by a range of ranks and trades. 100% had received mandatory training on the auto
      injector and over 70% had received more advanced training. Confidence in using
      the auto-injector was high, with 47% rating their confidence level as 10/10.
      Overall, factual knowledge was good with the mean score for the questionnaire
      being 7.9/10; 95% of respondents knew how to document the use of morphine and 79%
      knew when a second dose could safely be administered. Some misunderstanding of
      contraindications was revealed: 9% of answers were incorrect, and 47% wrongly
      answered that administering morphine to a patient changes the triage category.
      CONCLUSIONS: The majority of soldiers received far more than the minimum required
      training on the use of the morphine auto-injector. Confidence in using the device
      is high and generally knowledge is good. The authors suggest that deployed
      medical personnel in forward locations maintain regular training to soldiers on
      the morphine auto-injector in order to ensure that casualties receive analgesia
      appropriately and promptly.

PMID- 24566611
TI  - A pillared-layered zincoborate with an anionic network containing unprecedented
      zinc oxide chains.
AB  - A semiconducting zincoborate with a pillared-layered structure, has been prepared
      under solvothermal conditions, showing the first example of an inorganic-organic
      hybrid zincoborate with an anionic network based on the interesting zinc oxide
      chains linked by boron atoms and B3O7H2 clusters, which are further pillared by
      diamine molecules to form the 3-D framework. 

PMID- 24566612
TI  - Immediate effects of electroacupuncture and manual acupuncture on pain, mobility
      and muscle strength in patients with knee osteoarthritis: a randomised controlled
      trial.
AB  - OBJECTIVE: To compare the immediate effects of electroacupuncture and manual
      acupuncture on pain, mobility and muscle strength in patients with knee
      osteoarthritis. METHODS: Sixty patients with knee osteoarthritis, with a pain
      intensity of >=2 on the pain Numerical Rating Scale, were included. The patients
      were randomised into two groups: manual acupuncture and electroacupuncture. Pain
      intensity, degree of dysfunction (Timed Up and Go (TUG) test), maximal voluntary
      isometric contraction and pressure pain threshold were assessed before and after
      a single session of manual acupuncture or electroacupuncture treatments. RESULTS:
      Both groups showed a significant reduction in pain intensity (p<0.001) and time
      to run the TUG test after the acupuncture treatment (p=0.005 for the manual
      acupuncture group and p=0.002 for the electroacupuncture group). There were no
      differences between the groups regarding pain intensity (p=0.25), TUG test
      (p=0.70), maximum voluntary isometric contraction (p=0.43) or pressure pain
      threshold (p=0.27). CONCLUSIONS: This study found no difference between the
      immediate effects of a single session of manual acupuncture and
      electroacupuncture on pain, muscle strength and mobility in patients with knee
      osteoarthritis. TRIAL REGISTRATION NUMBER: RBR-9TCN2X.

PMID- 24566613
TI  - Impact of increasing ondansetron use on clinical outcomes in children with
      gastroenteritis.
AB  - IMPORTANCE: Ondansetron hydrochloride use in children with gastroenteritis is
      increasing rapidly; however, little is known about its impact on outcomes.
      OBJECTIVE: To determine whether increasing emergency department ondansetron use
      has resulted in a reduction in intravenous rehydration rates. DESIGN, SETTING,
      AND PARTICIPANTS: Retrospective observational analysis of eligible visits
      included in the Pediatric Health Information System administrative database.
      Eligible institutions included 18 emergency departments geographically
      distributed across the United States, and participants included 804,000 patients
      aged 0 to 18 years who were diagnosed as having gastroenteritis in an emergency
      department at an eligible participating institution between January 1, 2002, and
      December 31, 2011. INTERVENTIONS: The presence or absence of oral ondansetron
      administration was identified for each patient through database review. Visits
      were categorized based on institutional ondansetron use: low (<5% administered
      ondansetron), medium (5%-25%), or high (>25%). MAIN OUTCOMES AND MEASURES: We
      conducted hospital-level analyses of the associations between ondansetron use and
      3 outcomes: intravenous rehydration (primary), hospitalization, and emergency
      department revisits within 3 days. Time-series regression models were used,
      adjusting for demographic characteristics, laboratory testing, diagnostic
      imaging, and rotavirus infection. RESULTS: A total of 804,000 eligible patient
      visits were identified. Oral ondansetron use increased from a median
      institutional rate of 0.11% (interquartile range, 0.04%-0.44%) of patient visits
      in 2002 to 42.2% (interquartile range, 37.5%-49.1%) in 2011 (P < .001).
      Intravenous rehydration was administered to 43,413 of 232,706 children (18.7%)
      during the low ondansetron period compared with 59,450 of 334,264 (17.8%) during
      the high ondansetron period (adjusted percentage change = -0.33%; 95% CI, -1.86%
      to 1.20%). During the transition from low to high ondansetron use, we observed no
      change in the hospitalization rate (adjusted percentage change = -0.33%; 95% CI, 
      0.95% to 0.29%), but emergency department revisits decreased (adjusted percentage
      change = -0.31%; 95% CI, -0.49% to -0.13%). The change in all 3 outcomes varied
      widely between low and high ondansetron use categories at an institutional level.
      Oral ondansetron was provided to 13.5% (95% CI, 13.3% to 13.7%) of children
      administered intravenous rehydration. CONCLUSIONS AND RELEVANCE: Although
      ondansetron use increased during the study period, intravenous rehydration rates
      were unchanged. Most children administered intravenous fluids did not receive
      oral ondansetron. Our findings highlight the need to focus efforts to administer
      ondansetron to children at greatest risk for oral rehydration failure.

PMID- 24566614
TI  - Pharmacokinetic simulations to explore dissolution criteria of BCS I and III
      biowaivers with and without MDR-1 efflux transporter.
AB  - In this study, a pharmacokinetic simulation model was used to explore the
      dissolution acceptance criteria for BCS I and III biowaivers and to examine the
      risk of MDR-1 efflux transporter on bioequivalence of substrates. The
      compartmental absorption and transit (CAT) model with one- or two systemic
      compartments was used. The parameter values used in the simulations were based on
      the pharmacokinetics of existing 70 BCS I and III drugs. Based on the simulations
      BCS I drug products with Tmax of >0.9 h, both dissolution criteria "very rapid"
      and "rapid and similar" were acceptable. For rapidly absorbed and distributed BCS
      I drug products with Tmax of 0.6-0.9 h, the dissolution criterion "very rapid" is
      preferred. If Tmax is less than 0.6 h there is a risk of bioinequivalence for the
      BCS I drug products regardless of the dissolution criteria. Based on the
      simulations, all BCS III drug products were good biowaiver candidates with both
      dissolution criteria. Almost all the BCS III drug products (>89%) and many BCS I
      products (9-57%) showed risks of bioinequivalence, if an excipient in either
      product inhibits MDR1-efflux transport of the drug. To eliminate these risks
      excipients with prior use in bioequivalent products should be used for MDR-1
      efflux substrates.

PMID- 24566616
TI  - Maximizing the catalytic function of hydrogen spillover in platinum-encapsulated
      aluminosilicates with controlled nanostructures.
AB  - Hydrogen spillover has been studied for several decades, but its nature,
      catalytic functions and even its existence remain topics of vigorous debate. This
      is a consequence of the lack of model catalysts that can provide direct evidences
      of the existence of hydrogen spillover and simplify the catalytic interpretation.
      Here we use platinum encapsulated in a dense aluminosilicate matrix with
      controlled diffusional properties and surface hydroxyl concentrations to
      elucidate the catalytic functions of hydrogen spillover. The catalytic
      investigation and theoretical modelling show that surface hydroxyls, presumably
      Bronsted acids, are crucial for utilizing the catalytic functions of hydrogen
      spillover on the aluminosilicate surface. The catalysts with optimized
      nanostructure show remarkable activities in hydro-/dehydrogenation, but virtually
      no activity for hydrogenolysis. This distinct chemoselectivity may be beneficial
      in industrially important hydroconversions such as propane dehydrogenation to
      propylene because the undesired hydrogenolysis pathway producing light
      hydrocarbons of low value (methane and ethane) is greatly suppressed. 

PMID- 24566615
TI  - Immunosuppressive agent leflunomide: a SWNTs-immobilized dihydroortate
      dehydrogenase inhibitory effect and computational study of its adsorption
      properties on zigzag single walled (6,0) carbon and boron nitride nanotubes as
      controlled drug delivery devices.
AB  - Leflunomide [HWA 486 or RS-34821, 5-methyl-N-(4trifluoromethylphenyl)-4-isoxazole
      carboximide] is an immunosuppressive agent effective in the treatment of
      rheumatoid arthritis. Dihydroortate dehydrogenase (DHODH, EC 1.3.3.1)
      immobilization on the nanotubes was carried out and biochemical characterization
      of free and immobilized enzyme was determined. In comparison with free enzyme,
      the immobilized DHODH showed improved stability and reusability for investigation
      of inhibition pattern of drugs such as leflunomide. The experimental data showed
      that, DHODH was inhibited by the active metabolite of leflunomide (RS-61980) with
      a Ki and KI of 0.82 and 0.06 mM, respectively. Results exhibited mixed-type
      inhibition kinetics towards dihydroorotate as a substrate in the free and
      immobilized enzyme. Furthermore, the behavior of anticancer drug leflunomide
      adsorbed on the external surface of zigzag single walled (6,0) carbon and boron
      nitride nanotubes (SWCNT and SWBNNT) was studied by means of DFT calculations at
      the B3LYP/6-31G(*) level of theory. The larger adsorption energies and charges
      transfer showed that the adsorption of leflunomide onto SWBNNT is more stable
      than that the adsorption of leflunomide onto SWCNT. Frontier molecular orbitals
      (HOMO and LUMO) suggest that adsorption of leflunomide onto SWBNNT behave as
      charge transfer compounds with leflunomide as an electron donor and SWBNNT as an
      electron acceptor. Thus, nanotubes (NTs) have been proposed and actively explored
      as multipurpose innovative carriers for drug delivery and diagnostic application.
      The AIM theory has been also applied to analyze the properties of the bond
      critical points: their electron densities and their laplacians. Also, the natural
      bond orbital (NBO) calculations were performed to derive natural atomic orbital
      occupancies, and partial charges of the interacting atoms in the equilibrium tube
      molecule distance.

PMID- 24566617
TI  - Immunomodulatory glycan lacto-N-fucopentaose III requires clathrin-mediated
      endocytosis to induce alternative activation of antigen-presenting cells.
AB  - The mechanism of alternative activation of antigen-presenting cells (APCs) is
      largely unknown. Lacto-N-fucopentaose III (LNFPIII) is a biologically conserved
      pentasaccharide that contains the Lewis(x) trisaccharide. LNFPIII conjugates and
      schistosome egg antigens, which contain the Lewis(x) trisaccharide, drive
      alternative activation of APCs and induce anti-inflammatory responses in vivo,
      preventing inflammation-based diseases, including psoriasis, transplant organ
      rejection, and metabolic disease. In this study, we show that LNFPIII conjugates
      and schistosome egg antigens interact with APCs via a receptor-mediated process,
      requiring internalization of these molecules through a clathrin/dynamin-dependent
      but caveolus-independent endocytic pathway. Using inhibitors/small interfering
      RNA (siRNA) against dynamin and clathrin, we show for the first time that
      endocytosis of Lewis(x)-containing glycans is required to drive alternative
      maturation of antigen-presenting cells and Th2 immune responses. We identified
      mouse SIGNR-1 as a cell surface receptor for LNFPIII conjugates. Elimination of
      SIGNR-1 showed no effect on uptake of LNFPIII conjugates, suggesting that other
      receptors bind to and facilitate uptake of LNFPIII conjugates. We demonstrate
      that disruption of actin filaments partially prevented the entry of LNFPIII
      conjugates into APCs and that LNFPIII colocalizes with both early and late
      endosomal markers and follows the classical endosomal pathway leading to lysosome
      maturation. The results of this study show that the ability of LNFPIII to induce
      alternative activation utilizes a receptor-mediated process that requires a
      dynamin-dependent endocytosis. Thus, key steps have been defined in the
      previously unknown mechanism of alternative activation that ultimately leads to
      induction of anti-inflammatory responses. 

PMID- 24566618
TI  - Protection of human podocytes from shiga toxin 2-induced phosphorylation of
      mitogen-activated protein kinases and apoptosis by human serum amyloid P
      component.
AB  - Hemolytic uremic syndrome (HUS) is mainly induced by Shiga toxin 2 (Stx2)
      producing Escherichia coli. Proteinuria can occur in the early phase of the
      disease, and its persistence determines the renal prognosis. Stx2 may injure
      podocytes and induce proteinuria. Human serum amyloid P component (SAP), a member
      of the pentraxin family, has been shown to protect against Stx2-induced lethality
      in mice in vivo, presumably by specific binding to the toxin. We therefore tested
      the hypothesis that SAP can protect against Stx2-induced injury of human
      podocytes. To elucidate the mechanisms underlying podocyte injury in HUS
      associated proteinuria, we assessed Stx2-induced activation of mitogen-activated
      protein kinases (MAPKs) and apoptosis in immortalized human podocytes and
      evaluated the impact of SAP on Stx2-induced damage. Human podocytes express Stx2
      binding globotriaosylceramide 3. Stx2 applied to cultured podocytes was
      internalized and then activated p38alpha MAPK and c-Jun N-terminal kinase (JNK),
      important signaling steps in cell differentiation and apoptosis. Stx2 also
      activated caspase 3, resulting in an increased level of apoptosis. Coincubation
      of podocytes with SAP and Stx2 mitigated the effects of Stx2 and induced
      upregulation of antiapoptotic Bcl2. These data suggest that podocytes are a
      target of Stx2 and that SAP protects podocytes against Stx2-induced injury. SAP
      may therefore be a useful therapeutic option. 

PMID- 24566619
TI  - Neurons are host cells for Mycobacterium tuberculosis.
AB  - Mycobacterium tuberculosis infection of the central nervous system is thought to
      be initiated once the bacilli have breached the blood brain barrier and are
      phagocytosed, primarily by microglial cells. In this study, the interactions of
      M. tuberculosis with neurons in vitro and in vivo were investigated. The data
      obtained demonstrate that neurons can act as host cells for M. tuberculosis. M.
      tuberculosis bacilli were internalized by murine neuronal cultured cells in a
      time-dependent manner after exposure, with superior uptake by HT22 cells compared
      to Neuro-2a cells (17.7% versus 9.8%). Internalization of M. tuberculosis bacilli
      by human SK-N-SH cultured neurons suggested the clinical relevance of the
      findings. Moreover, primary murine hippocampus-derived neuronal cultures could
      similarly internalize M. tuberculosis. Internalized M. tuberculosis bacilli
      represented a productive infection with retention of bacterial viability and
      replicative potential, increasing 2- to 4-fold within 48 h. M. tuberculosis
      bacillus infection of neurons was confirmed in vivo in the brains of C57BL/6 mice
      after intracerebral challenge. This study, therefore, demonstrates neurons as
      potential new target cells for M. tuberculosis within the central nervous system.

PMID- 24566620
TI  - B-cell responses to pregnancy-restricted and -unrestricted Plasmodium falciparum
      erythrocyte membrane protein 1 antigens in Ghanaian women naturally exposed to
      malaria parasites.
AB  - Protective immunity to Plasmodium falciparum malaria acquired after natural
      exposure is largely antibody mediated. IgG-specific P. falciparum EMP1 (PfEMP1)
      proteins on the infected erythrocyte surface are particularly important. The
      transient antibody responses and the slowly acquired protective immunity probably
      reflect the clonal antigenic variation and allelic polymorphism of PfEMP1.
      However, it is likely that other immune-evasive mechanisms are also involved,
      such as interference with formation and maintenance of immunological memory. We
      measured PfEMP1-specific antibody levels by enzyme-linked immunosorbent assay
      (ELISA) and memory B-cell frequencies by enzyme-linked immunosorbent spot
      (ELISPOT) assay in a cohort of P. falciparum-exposed nonpregnant Ghanaian women.
      The antigens used were a VAR2CSA-type PfEMP1 (IT4VAR04) with expression
      restricted to parasites infecting the placenta, as well as two commonly
      recognized PfEMP1 proteins (HB3VAR06 and IT4VAR60) implicated in rosetting and
      not pregnancy restricted. This enabled, for the first time, a direct comparison
      in the same individuals of immune responses specific for a clinically important
      parasite antigen expressed only during well-defined periods (pregnancy) to
      responses specific for comparable antigens expressed independent of pregnancy.
      Our data indicate that PfEMP1-specific B-cell memory is adequately acquired even
      when antigen exposure is infrequent (e.g., VAR2CSA-type PfEMP1). Furthermore,
      immunological memory specific for VAR2CSA-type PfEMP1 can be maintained for many
      years without antigen reexposure and after circulating antigen-specific IgG has
      disappeared. The study provides evidence that natural exposure to P. falciparum
      leads to formation of durable B-cell immunity to clinically important PfEMP1
      antigens. This has encouraging implications for current efforts to develop PfEMP1
      based vaccines. 

PMID- 24566621
TI  - Escherichia coli pathotypes occupy distinct niches in the mouse intestine.
AB  - Since the first step of the infection process is colonization of the host, it is
      important to understand how Escherichia coli pathogens successfully colonize the
      intestine. We previously showed that enterohemorrhagic O157:H7 strain E. coli
      EDL933 colonizes a niche in the streptomycin-treated mouse intestine that is
      distinct from that of human commensal strains, which explains how E. coli EDL933
      overcomes colonization resistance imparted by some, but not all, commensal E.
      coli strains. Here we sought to determine if other E. coli pathogens use a
      similar strategy. We found that uropathogenic E. coli CFT073 and enteropathogenic
      E. coli E2348/69 occupy intestinal niches that are distinct from that of E. coli
      EDL933. In contrast, two enterohemorrhagic strains, E. coli EDL933 and E. coli
      Sakai, occupy the same niche, suggesting that strategies to prevent colonization
      by a given pathotype should be effective against other strains of the same
      pathotype. However, we found that a combination of commensal E. coli strains that
      can prevent colonization by E. coli EDL933 did not prevent colonization by E.
      coli CFT073 or E. coli E2348/69. Our results indicate that development of
      probiotics to target multiple E. coli pathotypes will be problematic, as the
      factors that govern niche occupation and hence stable colonization vary
      significantly among strains. 

PMID- 24566622
TI  - Diverse Toll-like receptors mediate cytokine production by Fusobacterium
      nucleatum and Aggregatibacter actinomycetemcomitans in macrophages.
AB  - Toll-like receptors (TLRs) orchestrate a repertoire of immune responses in
      macrophages against various pathogens. Fusobacterium nucleatum and
      Aggregatibacter actinomycetemcomitans are two important periodontal pathogens. In
      the present study, we investigated TLR signaling regulating cytokine production
      of macrophages in response to F. nucleatum and A. actinomycetemcomitans. TLR2 and
      TLR4 are redundant in the production of cytokines (interleukin-6 [IL-6] and tumor
      necrosis factor alpha [TNF-alpha]) in F. nucleatum- and A. actinomycetemcomitans
      infected macrophages. The production of cytokines by macrophages in response to
      F. nucleatum and A. actinomycetemcomitans infection was impaired in MyD88
      deficient macrophages. Moreover, cytokine concentrations were lower in MyD88
      deficient macrophages than in TLR2/TLR4 (TLR2/4) double-deficient cells. An
      endosomal TLR inhibitor, chloroquine, reduced cytokine production in TLR2/4
      deficient macrophages in response to F. nucleatum and A. actinomycetemcomitans,
      and DNA from F. nucleatum or A. actinomycetemcomitans induced IL-6 production in
      bone marrow-derived macrophages (BMDMs), which was abolished by chloroquine.
      Western blot analysis revealed that TLR2/4 and MyD88 were required for optimal
      activation of NF-kappaB and mitogen-activated protein kinases (MAPKs) in
      macrophages in response to F. nucleatum and A. actinomycetemcomitans, with
      different kinetics. An inhibitor assay showed that NF-kappaB and all MAPKs (p38,
      extracellular signal-regulated kinase [ERK], and Jun N-terminal protein kinase
      [JNK]) mediate F. nucleatum-induced production of cytokines in macrophages,
      whereas NF-kappaB and p38, but not ERK and JNK, are involved in A.
      actinomycetemcomitans-mediated cytokine production. These findings suggest that
      multiple TLRs may participate in the cytokine production of macrophages against
      periodontal bacteria. 

PMID- 24566623
TI  - Inflammatory bone loss in experimental periodontitis induced by Aggregatibacter
      actinomycetemcomitans in interleukin-1 receptor antagonist knockout mice.
AB  - The interleukin-1 receptor antagonist (IL-1Ra) binds to IL-1 receptors and
      inhibits IL-1 activity. However, it is not clear whether IL-1Ra plays a
      protective role in periodontal disease. This study was undertaken to compare
      experimental periodontitis induced by Aggregatibacter actinomycetemcomitans in IL
      1Ra knockout (KO) mice and wild-type (WT) mice. Computed tomography (CT) analysis
      and hematoxylin-and-eosin (H&E) and tartrate-resistant acid phosphatase (TRAP)
      staining were performed. In addition, osteoblasts were isolated; the mRNA
      expression of relevant genes was assessed by real-time quantitative PCR (qPCR);
      and calcification was detected by Alizarin Red staining. Infected IL-1Ra KO mice
      exhibited elevated (P, <0.05) levels of antibody against A.
      actinomycetemcomitans, bone loss in furcation areas, and alveolar fenestrations.
      Moreover, protein for tumor necrosis factor alpha (TNF-alpha) and IL-6, mRNA for
      macrophage colony-stimulating factor (M-CSF), and receptor activator of NF-kappaB
      ligand (RANKL) in IL-1Ra KO mouse osteoblasts stimulated with A.
      actinomycetemcomitans were increased (P, <0.05) compared to in WT mice. Alkaline
      phosphatase (ALP), bone sialoprotein (BSP), osteocalcin (OCN)/bone gla protein
      (BGP), and runt-related gene 2 (Runx2) mRNA levels were decreased (P, <0.05). IL
      1alpha mRNA expression was increased, and calcification was not observed, in IL-1
      Ra KO mouse osteoblasts. In brief, IL-1Ra deficiency promoted the expression of
      inflammatory cytokines beyond IL-1 and altered the expression of genes involved
      in bone resorption in A. actinomycetemcomitans-infected osteoblasts. Alterations
      consistent with rapid bone loss in infected IL-Ra KO mice were also observed for
      genes expressed in bone formation and calcification. In short, these data suggest
      that IL-1Ra may serve as a potential therapeutic drug for periodontal disease. 

PMID- 24566625
TI  - Attenuation of intestinal inflammation in interleukin-10-deficient mice infected
      with Citrobacter rodentium.
AB  - Interleukin-10 (IL-10) curtails immune responses to microbial infection and
      autoantigens and contributes to intestinal immune homeostasis, yet administration
      of IL-10 has not been effective at attenuating chronic intestinal inflammatory
      conditions, suggesting that its immune functions may be context dependent. To
      gain a broader understanding of the importance of IL-10 in controlling mucosal
      immune responses to infectious challenges, we employed the murine attaching and
      effacing pathogen Citrobacter rodentium, which colonizes primarily the surfaces
      of the cecum and colon and causes transient mucosal inflammation driven by Th17
      and Th1 T helper cells. Infection induced macrophage and dendritic cell
      production of IL-10, which diminished antibacterial host defenses, because IL-10
      deficient mice cleared infection faster than wild-type controls. In parallel, the
      mice had less acute infection-associated colitis and resolved it more rapidly
      than controls. Importantly, transient C. rodentium infection protected IL-10
      deficient mice against the later development of spontaneous colitis that normally
      occurs with aging in these mice. Genome-wide expression studies revealed that IL
      10 deficiency was associated with downregulation of proinflammatory pathways but
      increased expression of the anti-inflammatory cytokine IL-27 in response to
      infection. IL-27 was found to suppress in vitro Th17 and, to a lesser degree, Th1
      differentiation independent of IL-10. Furthermore, neutralization of IL-27
      resulted in more severe colitis in infected IL-10-deficient mice. Together, these
      findings indicate that IL-10 is dispensable for resolving C. rodentium-associated
      colitis and further suggest that IL-27 may be a critical factor for controlling
      intestinal inflammation and Th17 and Th1 development by IL-10-independent
      mechanisms. 

PMID- 24566624
TI  - Genetic variation on the BAT1-NFKBIL1-LTA region of major histocompatibility
      complex class III associates with periodontitis.
AB  - Periodontitis is a chronic inflammatory disease with a multifactorial etiology.
      We investigated whether human major histocompatibility complex (MHC)
      polymorphisms (6p21.3) are associated with periodontal parameters. Parogene 1
      population samples (n = 169) were analyzed with 13,245 single nucleotide
      polymorphisms (SNPs) of the MHC region. Eighteen selected SNPs (P <= 0.001) were
      replicated in Parogene 2 population samples (n = 339) and the Health 2000 Survey
      (n = 1,420). All subjects had a detailed clinical and radiographic oral health
      examination. Serum lymphotoxin-alpha (LTA) concentrations were measured in the
      Parogene populations, and the protein was detected in inflamed periodontal
      tissue. In the Parogene 1 population, 10 SNPs were associated with periodontal
      parameters. The strongest associations emerged from the parameters bleeding on
      probing (BOP) and a probing pocket depth (PPD) of >=6 mm with the genes BAT1,
      NFKBIL1, and LTA. Six SNPs, rs11796, rs3130059, rs2239527, rs2071591, rs909253,
      and rs1041981 (r(2), >=0.92), constituted a risk haplotype. In the Parogene 1
      population, the haplotype had the strongest association with the parameter BOP, a
      PPD of >=6 mm, and severe periodontitis with odds ratios (95% confidence
      intervals) of 2.63 (2.21 to 3.20), 2.90 (2.37 to 3.52), and 3.10 (1.63 to 5.98),
      respectively. These results were replicated in the other two populations. High
      serum LTA concentrations in the Parogene population were associated with the
      periodontitis risk alleles of the LTA SNPs (rs909253 and rs1041981) of the
      haplotype. In addition, the protein was expressed in inflamed gingival connective
      tissue. We identified a novel BAT1-NFKBIL1-LTA haplotype as a significant
      contributor to the risk of periodontitis. The genetic polymorphisms in the MHC
      class III region may be functionally important in periodontitis susceptibility. 

PMID- 24566627
TI  - Invasion of oral and aortic tissues by oral spirochete Treponema denticola in
      ApoE(-/-) mice causally links periodontal disease and atherosclerosis.
AB  - Treponema denticola is a predominantly subgingival oral spirochete closely
      associated with periodontal disease and has been detected in atherosclerosis.
      This study was designed to evaluate causative links between periodontal disease
      induced by chronic oral T. denticola infection and atherosclerosis in
      hyperlipidemic ApoE(-/-) mice. ApoE(-/-) mice (n = 24) were orally infected with
      T. denticola ATCC 35404 and were euthanized after 12 and 24 weeks. T. denticola
      genomic DNA was detected in oral plaque samples, indicating colonization of the
      oral cavity. Infection elicited significantly (P = 0.0172) higher IgG antibody
      levels and enhanced intrabony defects than sham infection. T. denticola-infected
      mice had higher levels of horizontal alveolar bone resorption than sham-infected
      mice and an associated significant increase in aortic plaque area (P <= 0.05).
      Increased atherosclerotic plaque correlated with reduced serum nitric oxide (NO)
      levels and increased serum-oxidized low-density lipoprotein (LDL) levels compared
      to those of sham-infected mice. T. denticola infection altered the expression of
      genes known to be involved in atherosclerotic development, including the
      leukocyte/endothelial cell adhesion gene (Thbs4), the connective tissue growth
      factor gene (Ctgf), and the selectin-E gene (Sele). Fluorescent in situ
      hybridization (FISH) revealed T. denticola clusters in both gingival and aortic
      tissue of infected mice. This is the first study examining the potential
      causative role of chronic T. denticola periodontal infection and vascular
      atherosclerosis in vivo in hyperlipidemic ApoE(-/-) mice. T. denticola is closely
      associated with periodontal disease and the rapid progression of atheroma in
      ApoE(-/-) mice. These studies confirm a causal link for active oral T. denticola
      infection with both atheroma and periodontal disease. 

PMID- 24566626
TI  - DhhP, a cyclic di-AMP phosphodiesterase of Borrelia burgdorferi, is essential for
      cell growth and virulence.
AB  - Cyclic di-AMP (c-di-AMP) is a recently discovered second messenger in bacteria.
      Most of work on c-di-AMP signaling has been done in Gram-positive bacteria,
      firmicutes, and actinobacteria, where c-di-AMP signaling pathways affect
      potassium transport, cell wall structure, and antibiotic resistance. Little is
      known about c-di-AMP signaling in other bacteria. Borrelia burgdorferi, the
      causative agent of Lyme disease, is a spirochete that has a Gram-negative dual
      membrane. In this study, we demonstrated that B. burgdorferi BB0619, a DHH-DHHA1
      domain protein (herein designated DhhP), functions as c-di-AMP phosphodiesterase.
      Recombinant DhhP hydrolyzed c-di-AMP to pApA in a Mn(2+)- or Mg(2+)-dependent
      manner. In contrast to c-di-AMP phosphodiesterases reported thus far, DhhP
      appears to be essential for B. burgdorferi growth both in vitro and in the
      mammalian host. Inactivation of the chromosomal dhhP gene could be achieved only
      in the presence of a plasmid-encoded inducible dhhP gene. The conditional dhhP
      mutant had a dramatic increase in intracellular c-di-AMP level in comparison to
      the isogenic wild-type strain. Unlike what has been observed in Gram-positive
      bacteria, elevated cellular c-di-AMP in B. burgdorferi did not result in an
      increased resistance to beta-lactamase antibiotics, suggesting that c-di-AMP's
      functions in spirochetes differ from those in Gram-positive bacteria. In
      addition, the dhhP mutant was defective in induction of the sigma(S) factor,
      RpoS, and the RpoS-dependent outer membrane virulence factor OspC, which uncovers
      an important role of c-di-AMP in B. burgdorferi virulence. 

PMID- 24566628
TI  - An ethA-ethR-deficient Mycobacterium bovis BCG mutant displays increased
      adherence to mammalian cells and greater persistence in vivo, which correlate
      with altered mycolic acid composition.
AB  - Tuberculosis remains a major worldwide epidemic because of its sole etiological
      agent, Mycobacterium tuberculosis. Ethionamide (ETH) is one of the major
      antitubercular drugs used to treat infections with multidrug-resistant M.
      tuberculosis strains. ETH is a prodrug that requires activation within the
      mycobacterial cell; its bioactivation involves the ethA-ethR locus, which encodes
      the monooxygenase EthA, while EthR is a transcriptional regulator that binds to
      the intergenic promoter region of the ethA-ethR locus. While most studies have
      focused on the role of EthA-EthR in ETH bioactivation, its physiological role in
      mycobacteria has remained elusive, although a role in bacterial cell
      detoxification has been proposed. Moreover, the importance of EthA-EthR in vivo
      has never been reported on. Here we constructed and characterized an EthA-EthR
      deficient mutant of Mycobacterium bovis BCG. Our results indicate that absence of
      the ethA-ethR locus led to greater persistence of M. bovis BCG in the mouse model
      of mycobacterial infection, which correlated with greater adherence to mammalian
      cells. Furthermore, analysis of cell wall lipid composition by thin-layer
      chromatography and mass spectrometry revealed differences between the ethA-ethR
      KO mutant and the parental strain in the relative amounts of alpha- and keto
      mycolates. Therefore, we propose here that M. bovis BCG ethA-ethR is involved in
      the cell wall-bound mycolate profile, which impacts mycobacterial adherence
      properties and in vivo persistence. This study thus provides some experimental
      clues to the possible physiological role of ethA-ethR and proposes that this
      locus is a novel factor involved in the modulation of mycobacterial virulence. 

PMID- 24566631
TI  - Driving-simulator-based test on the effectiveness of auditory red-light running
      vehicle warning system based on time-to-collision sensor.
AB  - The collision avoidance warning system is an emerging technology designed to
      assist drivers in avoiding red-light running (RLR) collisions at intersections.
      The aim of this paper is to evaluate the effect of auditory warning information
      on collision avoidance behaviors in the RLR pre-crash scenarios and further to
      examine the casual relationships among the relevant factors. A driving-simulator
      based experiment was designed and conducted with 50 participants. The data from
      the experiments were analyzed by approaches of ANOVA and structural equation
      modeling (SEM). The collisions avoidance related variables were measured in terms
      of brake reaction time (BRT), maximum deceleration and lane deviation in this
      study. It was found that the collision avoidance warning system can result in
      smaller collision rates compared to the without-warning condition and lead to
      shorter reaction times, larger maximum deceleration and less lane deviation.
      Furthermore, the SEM analysis illustrate that the audio warning information in
      fact has both direct and indirect effect on occurrence of collisions, and the
      indirect effect plays a more important role on collision avoidance than the
      direct effect. Essentially, the auditory warning information can assist drivers
      in detecting the RLR vehicles in a timely manner, thus providing drivers more
      adequate time and space to decelerate to avoid collisions with the conflicting
      vehicles. 

PMID- 24566629
TI  - Symbiotic relationship between Streptococcus mutans and Candida albicans
      synergizes virulence of plaque biofilms in vivo.
AB  - Streptococcus mutans is often cited as the main bacterial pathogen in dental
      caries, particularly in early-childhood caries (ECC). S. mutans may not act
      alone; Candida albicans cells are frequently detected along with heavy infection
      by S. mutans in plaque biofilms from ECC-affected children. It remains to be
      elucidated whether this association is involved in the enhancement of biofilm
      virulence. We showed that the ability of these organisms together to form
      biofilms is enhanced in vitro and in vivo. The presence of C. albicans augments
      the production of exopolysaccharides (EPS), such that cospecies biofilms accrue
      more biomass and harbor more viable S. mutans cells than single-species biofilms.
      The resulting 3-dimensional biofilm architecture displays sizeable S. mutans
      microcolonies surrounded by fungal cells, which are enmeshed in a dense EPS-rich
      matrix. Using a rodent model, we explored the implications of this cross-kingdom
      interaction for the pathogenesis of dental caries. Coinfected animals displayed
      higher levels of infection and microbial carriage within plaque biofilms than
      animals infected with either species alone. Furthermore, coinfection
      synergistically enhanced biofilm virulence, leading to aggressive onset of the
      disease with rampant carious lesions. Our in vitro data also revealed that
      glucosyltransferase-derived EPS is a key mediator of cospecies biofilm
      development and that coexistence with C. albicans induces the expression of
      virulence genes in S. mutans (e.g., gtfB, fabM). We also found that Candida
      derived beta1,3-glucans contribute to the EPS matrix structure, while fungal
      mannan and beta-glucan provide sites for GtfB binding and activity. Altogether,
      we demonstrate a novel mutualistic bacterium-fungus relationship that occurs at a
      clinically relevant site to amplify the severity of a ubiquitous infectious
      disease. 

PMID- 24566632
TI  - Sparse representations-based super-resolution of key-frames extracted from frames
      sequences generated by a visual sensor network.
AB  - Visual sensor networks (VSNs) usually generate a low-resolution (LR) frame
      sequence due to energy and processing constraints. These LR-frames are not very
      appropriate for use in certain surveillance applications. It is very important to
      enhance the resolution of the captured LR-frames using resolution enhancement
      schemes. In this paper, an effective framework for a super-resolution (SR) scheme
      is proposed that enhances the resolution of LR key-frames extracted from frame
      sequences captured by visual-sensors. In a VSN, a visual processing hub (VPH)
      collects a huge amount of visual data from camera sensors. In the proposed
      framework, at the VPH, key-frames are extracted using our recent key-frame
      extraction technique and are streamed to the base station (BS) after compression.
      A novel effective SR scheme is applied at BS to produce a high-resolution (HR)
      output from the received key-frames. The proposed SR scheme uses optimized
      orthogonal matching pursuit (OOMP) for sparse-representation recovery in SR. OOMP
      does better in terms of detecting true sparsity than orthogonal matching pursuit
      (OMP). This property of the OOMP helps produce a HR image which is closer to the
      original image. The K-SVD dictionary learning procedure is incorporated for
      dictionary learning. Batch-OMP improves the dictionary learning process by
      removing the limitation in handling a large set of observed signals. Experimental
      results validate the effectiveness of the proposed scheme and show its
      superiority over other state-of-the-art schemes. 

PMID- 24566630
TI  - Host inflammatory response inhibits Escherichia coli O157:H7 adhesion to gut
      epithelium through augmentation of mucin expression.
AB  - Escherichia coli O157:H7, a major Shiga toxin-producing pathogen, has a low
      infectious dose and causes serious illness in humans. The gastrointestinal tract
      of cattle is the primary reservoir of E. coli O157:H7, and thus, it is critical
      to eliminate or reduce E. coli O157:H7 gut colonization. Given that E. coli
      O157:H7 produces effectors that attenuate inflammatory signaling, we hypothesized
      that the host inflammatory response acts to perturb E. coli O157:H7 intestinal
      colonization. Tumor necrosis factor alpha (TNF-alpha) treatment of HT-29 cells
      resulted in increased expression of inflammatory cytokine interleukin 1beta (IL
      1beta), IL-8, and TNF-alpha genes and increased IL-8 protein and resulted in
      decreased adhesion of E. coli O157:H7. Similarly, E. coli O157:H7 adhesion to
      cattle colonic explants was reduced by TNF-alpha treatment. Irrespective of the
      presence of E. coli O157:H7, TNF-alpha enhanced activation of p65, the key
      mediator of NF-kappaB inflammatory signaling, whereas E. coli O157:H7 infection
      suppressed this pathway by inhibiting p65 activation in HT-29 cells. To further
      explore the mechanisms linking the inflammatory response to attenuated E. coli
      O157:H7 adhesion, mucin 2 (MUC2) expression was analyzed, considering that the
      intestinal mucus layer is the first defense against enteric pathogens and MUC2 is
      the major secretory mucin in the intestine. MUC2 expression in HT-29 cells was
      increased by TNF-alpha treatment and by E. coli O157:H7 infection. However,
      reducing mucin expression by blocking mitogen-activated protein kinase (MAPK)
      extracellular signal-regulated protein kinases 1/2 (ERK1/2) and/or
      phosphatidylinositol 3-kinase (PI3K)/Akt signaling increased E. coli O157:H7
      adherence to HT-29 cells. These data suggest that the inflammatory cytokine
      response acts to protect host epithelial cells against E. coli O157:H7
      colonization, at least in part, by promoting mucin production. 

PMID- 24566633
TI  - Description of an advantageous optical label-free biosensing interferometric read
      out method to measure biological species.
AB  - In this article we report a new, simple, and reliable optical read-out detection
      method able to assess Rotavirus present in human sera as well as in the viral
      pollution sources. It is based on the interference of two interferometers used as
      biophotonic transducers. The method significantly improves the optical label-free
      biosensing response measuring both, the concentration of the AgR and its
      corresponding size. Two different immunoassays were carried out: Bovine Serum
      Albumin (BSA), and the recognition by its antibody (anti-BSA); and Rotavirus
      (AgR) and the recognition by its antibody (anti-AgR). In the cases studied, and
      using as model interferometer a simple Fabry-Perot transducer, we demonstrate a
      biosensing enhancement of two orders of magnitude in the Limit of Detection
      (LoD). In fact, this read-out optical method may have significant implications to
      enhance other optical label-free photonic transducers reported in the scientific
      literature. 

PMID- 24566634
TI  - Feature point descriptors: infrared and visible spectra.
AB  - This manuscript evaluates the behavior of classical feature point descriptors
      when they are used in images from long-wave infrared spectral band and compare
      them with the results obtained in the visible spectrum. Robustness to changes in
      rotation, scaling, blur, and additive noise are analyzed using a state of the art
      framework. Experimental results using a cross-spectral outdoor image data set are
      presented and conclusions from these experiments are given. 

PMID- 24566635
TI  - An analysis of the precision and reliability of the leap motion sensor and its
      suitability for static and dynamic tracking.
AB  - We present the results of an evaluation of the performance of the Leap Motion
      Controller with the aid of a professional, high-precision, fast motion tracking
      system. A set of static and dynamic measurements was performed with different
      numbers of tracking objects and configurations. For the static measurements, a
      plastic arm model simulating a human arm was used. A set of 37 reference
      locations was selected to cover the controller's sensory space. For the dynamic
      measurements, a special V-shaped tool, consisting of two tracking objects
      maintaining a constant distance between them, was created to simulate two human
      fingers. In the static scenario, the standard deviation was less than 0.5 mm. The
      linear correlation revealed a significant increase in the standard deviation when
      moving away from the controller. The results of the dynamic scenario revealed the
      inconsistent performance of the controller, with a significant drop in accuracy
      for samples taken more than 250 mm above the controller's surface. The Leap
      Motion Controller undoubtedly represents a revolutionary input device for gesture
      based human-computer interaction; however, due to its rather limited sensory
      space and inconsistent sampling frequency, in its current configuration it cannot
      currently be used as a professional tracking system. 

PMID- 24566636
TI  - Wavelet-based watermarking and compression for ECG signals with verification
      evaluation.
AB  - In the current open society and with the growth of human rights, people are more
      and more concerned about the privacy of their information and other important
      data. This study makes use of electrocardiography (ECG) data in order to protect
      individual information. An ECG signal can not only be used to analyze disease,
      but also to provide crucial biometric information for identification and
      authentication. In this study, we propose a new idea of integrating
      electrocardiogram watermarking and compression approach, which has never been
      researched before. ECG watermarking can ensure the confidentiality and
      reliability of a user's data while reducing the amount of data. In the
      evaluation, we apply the embedding capacity, bit error rate (BER), signal-to
      noise ratio (SNR), compression ratio (CR), and compressed-signal to noise ratio
      (CNR) methods to assess the proposed algorithm. After comprehensive evaluation
      the final results show that our algorithm is robust and feasible. 

PMID- 24566637
TI  - DNA-aptamers binding aminoglycoside antibiotics.
AB  - Aptamers are short, single stranded DNA or RNA oligonucleotides that are able to
      bind specifically and with high affinity to their non-nucleic acid target
      molecules. This binding reaction enables their application as biorecognition
      elements in biosensors and assays. As antibiotic residues pose a problem
      contributing to the emergence of antibiotic-resistant pathogens and thereby
      reducing the effectiveness of the drug to fight human infections, we selected
      aptamers targeted against the aminoglycoside antibiotic kanamycin A with the aim
      of constructing a robust and functional assay that can be used for water
      analysis. With this work we show that aptamers that were derived from a Capture
      SELEX procedure targeting against kanamycin A also display binding to related
      aminoglycoside antibiotics. The binding patterns differ among all tested aptamers
      so that there are highly substance specific aptamers and more group specific
      aptamers binding to a different variety of aminoglycoside antibiotics. Also the
      region of the aminoglycoside antibiotics responsible for aptamer binding can be
      estimated. Affinities of the different aptamers for their target substance,
      kanamycin A, are measured with different approaches and are in the micromolar
      range. Finally, the proof of principle of an assay for detection of kanamycin A
      in a real water sample is given. 

PMID- 24566638
TI  - A population model for predicting the successful establishment of introduced bird
      species.
AB  - One of the strongest generalities in invasion biology is the positive
      relationship between probability of establishment and the numbers of individuals
      introduced. Nevertheless, a number of significant questions remain regarding: (1)
      the relative importance of different processes during introduction (e.g.,
      demographic, environmental, and genetic stochasticity, and Allee effects); (2)
      the relative effects of propagule pressure (e.g., number of introductions, size
      of introductions, and lag between introductions); and (3) different life history
      characteristics of the species themselves. Here, we adopt an individual-based
      simulation modeling approach to explore a range of such details in the
      relationship between establishment success and numbers of individuals introduced.
      Our models are developed for typical exotic bird introductions, for which the
      relationship between probability of establishment and the numbers of individuals
      introduced has been particularly well documented. For both short-lived and long
      lived species, probability of establishment decreased across multiple
      introductions (compared with a single introduction of the same total size), and
      this decrease was greater when inbreeding depression was included. Sensitivity
      analyses revealed four predictors that together accounted for >95% of model
      performance. Of these, R 0 (the average number of daughters produced per female
      over her lifetime) and propagule pressure were of primary importance, while
      random environmental effects and inbreeding depression exerted lesser influence.
      Initial founder size is undoubtedly going to be important for ensuring the
      persistence of introduced populations. However, we found the demographic traits,
      which influence how introduced individuals behave, to have the greatest effect on
      establishment success.

PMID- 24566639
TI  - Parasite modification of predator functional response.
AB  - Parasite alteration of the host (predator) functional response provides a
      mechanism by which parasites can alter predator-prey population dynamics and
      stability. We tested the hypothesis that parasitic infection of a crab
      (Eurypanopeus depressus) by a rhizocephalan barnacle (Loxothylacus panopei) can
      modify the crab's functional response to mussel (Brachidontes exustus) prey and
      investigated behavioral mechanisms behind a potential change in the response.
      Infection dramatically reduced mussel consumption by crabs across mussel
      densities, resulting in a decreased attack rate parameter and a nearly eightfold
      reduction in maximum consumption (i.e. the asymptote, or inverse of the handling
      time parameter) in a type II functional response model. To test whether increased
      handling time of infected crabs drove the decrease in maximum consumption rate,
      we independently measured handling time through observation. Infection had no
      effect on handling time and thus could not explain the reduction in consumption.
      Infection did, however, increase the time that it took crabs to begin handling
      prey after the start of the handling time experiment. Furthermore, crabs
      harboring relatively larger parasites remained inactive longer before making
      contact with prey. This behavioral modification likely contributed to the reduced
      mussel consumption of infected crabs. A field survey revealed that 20% of crabs
      inhabiting oyster reefs at the study site (North Inlet estuary, Georgetown, South
      Carolina, USA) are infected by the barnacle parasite, indicating that parasite
      infection could have a substantial effect on the population level crab-mussel
      interaction.

PMID- 24566640
TI  - Characterization of cost with respect to nutritional upshift in the media
      composition along with sublethal doses of transcriptional and translational
      inhibitor.
AB  - Expression of unnecessary proteins is known to reduce the growth rate of
      Escherichia coli. This reduction in growth rate, due to the diversion of cellular
      resources from making essential proteins, is called cost. Cellular resources
      depend upon the macromolecular content of the cell. Cost phenomenon lies in the
      process of transcription and translation. The effect of an upshift in the
      nutritional content of the medium on the cost process of natural lac proteins is
      not looked upon. Which process of gene expression, transcription, or translation
      is more important for the cost process is not clear. The current study indicated
      that cost process is not associated with the upshift mechanism. Cost process was
      not observed in presence of rifampicin but was detected in existence of
      chloramphenicol. The current study will help in better understanding of the cost
      process. 

PMID- 24566641
TI  - Improving access to lung cancer treatment in northern Canada: the role of oral
      molecularly targeted agents.

PMID- 24566644
TI  - Consent to publish is a matter of trust.

PMID- 24566645
TI  - Address extreme violence in Central African Republic now: MSF.

PMID- 24566643
TI  - Prevalence of and risk factors for persistent postoperative nonanginal pain after
      cardiac surgery: a 2-year prospective multicentre study.
AB  - BACKGROUND: Persistent postoperative pain continues to be an underrecognized
      complication. We examined the prevalence of and risk factors for this type of
      pain after cardiac surgery. METHODS: We enrolled patients scheduled for coronary
      artery bypass grafting or valve replacement, or both, from Feb. 8, 2005, to Sept.
      1, 2009. Validated measures were used to assess (a) preoperative anxiety and
      depression, tendency to catastrophize in the face of pain, health-related quality
      of life and presence of persistent pain; (b) pain intensity and interference in
      the first postoperative week; and (c) presence and intensity of persistent
      postoperative pain at 3, 6, 12 and 24 months after surgery. The primary outcome
      was the presence of persistent postoperative pain during 24 months of follow-up.
      RESULTS: A total of 1247 patients completed the preoperative assessment. Follow
      up retention rates at 3 and 24 months were 84% and 78%, respectively. The
      prevalence of persistent postoperative pain decreased significantly over time,
      from 40.1% at 3 months to 22.1% at 6 months, 16.5% at 12 months and 9.5% at 24
      months; the pain was rated as moderate to severe in 3.6% at 24 months. Acute
      postoperative pain predicted both the presence and severity of persistent
      postoperative pain. The more intense the pain during the first week after surgery
      and the more it interfered with functioning, the more likely the patients were to
      report persistent postoperative pain. Pre-existing persistent pain and increased
      preoperative anxiety also predicted the presence of persistent postoperative
      pain. INTERPRETATION: Persistent postoperative pain of nonanginal origin after
      cardiac surgery affected a substantial proportion of the study population. Future
      research is needed to determine whether interventions to modify certain risk
      factors, such as preoperative anxiety and the severity of pain before and
      immediately after surgery, may help to minimize or prevent persistent
      postoperative pain.

PMID- 24566646
TI  - Chikungunya fever in Canada: fever and polyarthritis in a returned traveller.

PMID- 24566647
TI  - National summit on physician employment finds no quick fixes for specialist job
      shortages.

PMID- 24566649
TI  - US stroke guidelines provoke mixed reaction.

PMID- 24566650
TI  - Canada needs a "dialogue about death," says CMA president.

PMID- 24566652
TI  - Carpal tunnel syndrome.

PMID- 24566651
TI  - Sjogren syndrome.

PMID- 24566653
TI  - [Informed consent of the surgical patient].
AB  - The article analyses the consequences of the paradigm shift in the surgical
      practice in the last fifty years. The earlier, paternalistic physician-patient
      relationship has been replaced by an equal one, which is based on informing the
      patient and involving him or her in the treatment decisions. This shift did not
      happen uniformly in various medical subspecialties. In this respect, surgery is
      more conservative than general medicine. The article analyses the most frequent
      problems of informing patients, and examines the major elements of information,
      together with their technical conditions in surgery. It reflects on specifics of
      surgical information disclosure and conditions of refusing medical interventions.

PMID- 24566654
TI  - [Gastrointestinal locations of primary melanoma].
AB  - Primary gastrointestinal melanomas, part of the mucosal melanoma group, are
      uncommon. They constitute about five percent of all melanomas and most of them
      are located in the rectum (3 percent of all melanomas). The prognosis is poor,
      overall 5-year survival in rectal melanoma is 10-20 percent. We present three of
      our cases. The first case - a 68-year-old male patient - was operated on for
      histologically proved rectal melanoma. Three years after radical excision and
      oncological treatment a metastasis of the primary tumor was diagnosed in the
      stomach. Total gastrectomy was performed, followed by oncological treatment. In
      the second case of a 59-year-old male patient an appendectomy was performed for
      symptoms of appendicitis. The histopathological examination revealed melanoma of
      the appendix. Further investigations revealed the primary tumor in the stomach
      and metastases in the lungs as well. The third case - an 82-year-old female
      patient - was investigated for frequent defecations, mucus in stool and fecal
      incontinence. Primary melanoma was proved in the lower third of the rectum with
      multiple hepatic metastases. These three cases in our practice are remarkable for
      the rarity of the disease, and in two cases the presence of both the primary
      tumor and the metastasis were located in the gastrointestinal tract. 

PMID- 24566655
TI  - [TEO: minimally invasive surgery of the rectum. A short review].
AB  - The equipment and technique of transanal endoscopic microsurgery was developed by
      Buess in the early 80s. The technique was more refined, and the indication was
      widened since then. Excellent oncological results can be achieved with good
      patient selection with this less invasive technique and the complication rate is
      very low in contrast to conventional techniques. Nowadays the transanal
      endoscopic microsurgery is the "gold standard" in the treatment of benign lesions
      and low risk T1 cancer of the rectum. 

PMID- 24566656
TI  - [Autoimmune pancreatitis mimicking pancreatic tumor].
AB  - Autoimmune pancreatitis (AIP) is a rare disease of unknown pathomechanism. AIP
      belongs to the IgG4-related disease family and responds well to steroids,
      although the relapse rate can reach up to 20-30%. Differentiation of AIP from the
      more common pancreatic cancer can be very challenging. About 20% of autoimmune
      pancreatitis is diagnosed postoperatively during final histological examination.
      While each of diagnostic investigations provide some additional information
      towards definitive diagnosis, the question still remains whether it is possible
      to prevent unnecessary pancreatic resection. We demonstrate the differential
      diagnostic opportunities when we present our case as well as discuss the
      literature data of this condition. In conclusion, we think that in case of a
      focal pancreatic lesion AIP should always be considered. 

PMID- 24566658
TI  - [Sentinel lymph nodes in breast cancer: some thoughts on the past and on the
      future in connection with the clinical practice at the Uzsoki Street Hospital].

PMID- 24566661
TI  - A prospective study on inflammatory parameters in obese patients after sleeve
      gastrectomy.
AB  - Different hormones and peptides involved in inflammation have been studied in and
      related to obesity. The aim of our work is to assess the variations of different
      molecules related to inflammation in obese patients during the first year
      following sleeve gastrectomy. This was a prospective study on patients who
      underwent sleeve gastrectomy. The variations in different clinical,
      anthropometric, and analytical parameters related to inflammation were determined
      and analysed in all patients at the preoperative visit and at the first and fifth
      days, first and sixth months, and 1 year following surgery. We enrolled 20
      patients to the study. The median body mass index (BMI) before intervention was
      48.5 kg/m2. With respect to comorbidities, 70% of the patients had obstructive
      sleep apnoea syndrome (OSA), 65% high blood pressure, 45% dyslipidaemia, and 40%
      diabetes mellitus (DM). The median percentage of BMI lost (%BMIL) 1 year after
      the intervention was 71%. The dyslipidaemia healing or improvement rate was 100%,
      whereas it was 87.5% for diabetes, 84.6% for hypertension, and 57.1% for OSA.
      During the 1-year postintervention period, the average levels of adiponectin
      increased, although not significantly, whereas those of leptin significantly
      decreased. In addition, the blood levels of MCP-1, IL-6, CRP, ferritin, and PAI-1
      significantly decreased in that period. Sleeve gastrectomy is a surgical
      technique that is associated with improvements in body weight and comorbid
      conditions from the first postoperative months, which lead to significant
      variations in the levels of different inflammation-related parameters and a
      decrease in the levels of leptin, IL-6, CRP, MCP-1, ferritin, and serpin (PAI-1).

PMID- 24566663
TI  - Lessons learned: challenges in applying current constraints on research on
      chimpanzees to other animals.
AB  - The Institute of Medicine (IOM) Committee on the Necessity of the Use of
      Chimpanzees in Biomedical and Behavioral Research made a series of
      recommendations that, as of an announcement on June 26, 2013, the National
      Institutes of Health (NIH) is turning into implemented guidelines. Many
      advocates, including some researchers and scholars, have suggested that the
      Committee's recommendations could be applied successfully to other animal
      species. This article examines, from my perspective as the IOM Committee's chair,
      some of the most important features of the Committee's work, addresses whether
      chimpanzees represent a special or unique case for the purpose of research
      policy, and suggests an approach for evaluating the applicability of the
      Committee's recommendations for other animal species used in research. I first
      present my perspective on the features of the Committee's work that influenced
      its approach and conclusions. I then argue that despite the fact that chimpanzees
      represent a somewhat unique case for restricted research use, their case still
      offers important lessons for policy regarding the use of other species. Finally,
      I offer some observations regarding the recommendations and implications of the
      report from the NIH Working Group charged with crafting guidelines for
      implementing the IOM Committee's recommendations. 

PMID- 24566662
TI  - Short-term outcomes of laparoscopic single anastomosis gastric bypass (LSAGB) for
      the treatment of type 2 diabetes in lower BMI (<30 kg/m(2)) patients.
AB  - BACKGROUND: Bariatric surgery is an efficient procedure for remission of type 2
      diabetes (T2DM) in morbid obesity. However, in Asian countries, mean body mass
      index (BMI) of T2DM patients is about 25 kg/m(2). Various data on patients
      undergoing gastric bypass surgery showed that control of T2DM after surgery
      occurs rapidly and somewhat independent to weight loss. We hypothesized that in
      non-obese patients with T2DM, the glycemic control would be achieved as a
      consequence of gastric bypass surgery. METHODS: From September 2009, the 172
      patients have had laparoscopic single anastomosis gastric bypass (LSAGB) surgery.
      Among them, 107 patients have been followed up more than 1 year. We analyzed the
      dataset of these patients. Values related to diabetes were measured before and 1,
      2, and 3 years after the surgery. RESULTS: The mean BMI decreased during the
      first year after the surgery but plateaued after that. The mean glycosylated
      hemoglobin level decreased continuously. The mean fasting and postglucose loading
      plasma glucose level also decreased. CONCLUSION: After LSAGB surgery in non-obese
      T2DM patients, the control of T2DM was possible safely and effectively. However,
      longer follow-up with matched control group is essential.

PMID- 24566664
TI  - Liquid filament instability due to stretch-induced phase separation in polymer
      solutions: Liquid filament instability.
AB  - The instability in a jet of a viscoelastic semidilute entangled polymer solution
      under high stretching is discussed. Initially the jet is stable due to solution
      elasticity stopping the fluctuation growth. The modeling shows that a jet
      stretching results in a radial gradient in the polymer distribution: the polymer
      is concentrated in the jet centre, whereas the solvent is remaining near the
      surface. This viscous liquid shell demonstrates Raleigh-type instability
      resulting in the formation of individual droplets on the oriented filament. All
      process stages were observed experimentally. 

PMID- 24566665
TI  - Low symmetry tetrahedral nematic liquid crystal phases: Ambidextrous chirality
      and ambidextrous helicity.
AB  - We discuss the symmetry properties as well as the dynamic behavior of various non
      polar nematic liquid crystal phases with tetrahedral order. We concentrate on
      systems that show biaxial nematic order coexisting with octupolar (tetrahedral)
      order. Non-polar examples are phases with D2 and S4 symmetries, which can be
      characterized as biaxial nematics lacking inversion symmetry. It is this
      combination that allows for new features in the statics and dynamics of these
      phases. The D2-symmetric phase is chiral, even for achiral molecules, and shows
      ambidextrous chirality in all three preferred directions. The achiral S4
      symmetric phase allows for ambidextrous helicity, similar to the higher-symmetric
      D2d-symmetric phase. Such phases are candidates for nematic phases made from
      banana-shaped molecules. 

PMID- 24566666
TI  - Polysaccharide-gold nanocluster supramolecular conjugates as a versatile platform
      for the targeted delivery of anticancer drugs.
AB  - Through the high affinity of the beta-cyclodextrin (beta-CD) cavity for
      adamantane moieties, novel polysaccharide-gold nanocluster supramolecular
      conjugates (HACD-AuNPs) were successfully constructed from gold nanoparticles
      (AuNPs) bearing adamantane moieties and cyclodextrin-grafted hyaluronic acid
      (HACD). Due to their porous structure, the supramolecular conjugates could serve
      as a versatile and biocompatible platform for the loading and delivery of various
      anticancer drugs, such as doxorubicin hydrochloride (DOX), paclitaxel (PTX),
      camptothecin (CPT), irinotecan hydrochloride (CPT-11), and topotecan
      hydrochloride (TPT), by taking advantage of the controlled
      association/dissociation of drug molecules from the cavities formed by the HACD
      skeletons and AuNPs cores as well as by harnessing the efficient targeting of
      cancer cells by hyaluronic acid. Significantly, the release of anticancer drugs
      from the drug@HACD-AuNPs system was pH-responsive, with more efficient release
      occurring under a mildly acidic environment, such as that in a cancer cell.
      Taking the anticancer drug DOX as an example, cell viability experiments revealed
      that the DOX@HACD-AuNPs system exhibited similar tumor cell inhibition abilities
      but lower toxicity than free DOX due to the hyaluronic acid reporter-mediated
      endocytosis. Therefore, the HACD-AuNPs supramolecular conjugates may possess
      great potential for the targeted delivery of anticancer drugs. 

PMID- 24566667
TI  - Multifactorial interaction of growth factors on Penaeus monodon lymphoid cells
      and the impact of IGFs in DNA synthesis and metabolic activity in vitro.
AB  - Development of continuous cell lines from shrimp is essential to investigate
      viral pathogens. Unfortunately, there is no valid cell line developed from
      crustaceans in general and shrimps in particular to address this issue. Lack of
      information on the requirements of cells in vitro limits the success of
      developing a cell line, where the microenvironment of a cell culture, provided by
      the growth medium, is of prime importance. Screening and optimization of growth
      medium components based on statistical experimental designs have been widely used
      for improving the efficacy of cell culture media. Accordingly, we applied
      Plackett-Burman design and response surface methodology to study multifactorial
      interactions between the growth factors in shrimp cell culture medium and to
      identify the most important ones for growth of lymphoid cell culture from Penaeus
      monodon. The statistical screening and optimization indicated that insulin like
      growth factor-I (IGF-I) and insulin like growth factor-II (IGF-II) at
      concentrations of 100 and 150 ng ml(-1), respectively, could significantly
      influence the metabolic activity and DNA synthesis of the lymphoid cells. An
      increase of 53 % metabolic activity and 24.8 % DNA synthesis could be obtained,
      which suggested that IGF-I and IGF-II had critical roles in metabolic activity
      and DNA synthesis of shrimp lymphoid cells. 

PMID- 24566669
TI  - Diagnostic serum glycosylation profile in patients with intellectual disability
      as a result of MAN1B1 deficiency.
AB  - Congenital disorders of glycosylation comprise a group of genetic defects with a
      high frequency of intellectual disability, caused by deficient glycosylation of
      proteins and lipids. The molecular basis of the majority of the congenital
      disorders of glycosylation type I subtypes, localized in the cytosol and
      endoplasmic reticulum, has been solved. However, elucidation of causative genes
      for defective Golgi glycosylation (congenital disorders of glycosylation type II)
      remains challenging because of a lack of sufficiently specific diagnostic serum
      methods. In a single patient with intellectual disability, whole-exome sequencing
      revealed MAN1B1 as congenital disorder of glycosylation type II candidate gene. A
      novel mass spectrometry method was applied for high-resolution glycoprofiling of
      intact plasma transferrin. A highly characteristic glycosylation signature was
      observed with hybrid type N-glycans, in agreement with deficient mannosidase
      activity. The speed and robustness of the method allowed subsequent screening in
      a cohort of 100 patients with congenital disorder of glycosylation type II, which
      revealed the characteristic glycosylation profile of MAN1B1-congenital disorder
      of glycosylation in 11 additional patients. Abnormal hybrid type N-glycans were
      also observed in the glycoprofiles of total serum proteins, of enriched
      immunoglobulins and of alpha1-antitrypsin in variable amounts. Sanger sequencing
      revealed MAN1B1 mutations in all patients, including severe truncating mutations
      and amino acid substitutions in the alpha-mannosidase catalytic site. Clinically,
      this group of patients was characterized by intellectual disability and delayed
      motor and speech development. In addition, variable dysmorphic features were
      noted, with truncal obesity and macrocephaly in ~65% of patients. In summary,
      MAN1B1 deficiency appeared to be a frequent cause in our cohort of patients with
      unsolved congenital disorder of glycosylation type II. Our method for analysis of
      intact transferrin provides a rapid test to detect MAN1B1-deficient patients
      within congenital disorder of glycosylation type II cohorts and can be used as
      efficient diagnostic method to identify MAN1B1-deficient patients in intellectual
      disability cohorts. In addition, it provides a functional confirmation of MAN1B1
      mutations as identified by next-generation sequencing in individuals with
      intellectual disability. 

PMID- 24566670
TI  - Resting state functional MRI in Parkinson's disease: the impact of deep brain
      stimulation on 'effective' connectivity.
AB  - Depleted of dopamine, the dynamics of the parkinsonian brain impact on both
      'action' and 'resting' motor behaviour. Deep brain stimulation has become an
      established means of managing these symptoms, although its mechanisms of action
      remain unclear. Non-invasive characterizations of induced brain responses, and
      the effective connectivity underlying them, generally appeals to dynamic causal
      modelling of neuroimaging data. When the brain is at rest, however, this sort of
      characterization has been limited to correlations (functional connectivity). In
      this work, we model the 'effective' connectivity underlying low frequency blood
      oxygen level-dependent fluctuations in the resting Parkinsonian motor network
      disclosing the distributed effects of deep brain stimulation on cortico
      subcortical connections. Specifically, we show that subthalamic nucleus deep
      brain stimulation modulates all the major components of the motor cortico-striato
      thalamo-cortical loop, including the cortico-striatal, thalamo-cortical, direct
      and indirect basal ganglia pathways, and the hyperdirect subthalamic nucleus
      projections. The strength of effective subthalamic nucleus afferents and
      efferents were reduced by stimulation, whereas cortico-striatal, thalamo-cortical
      and direct pathways were strengthened. Remarkably, regression analysis revealed
      that the hyperdirect, direct, and basal ganglia afferents to the subthalamic
      nucleus predicted clinical status and therapeutic response to deep brain
      stimulation; however, suppression of the sensitivity of the subthalamic nucleus
      to its hyperdirect afferents by deep brain stimulation may subvert the clinical
      efficacy of deep brain stimulation. Our findings highlight the distributed
      effects of stimulation on the resting motor network and provide a framework for
      analysing effective connectivity in resting state functional MRI with strong a
      priori hypotheses. 

PMID- 24566671
TI  - Leukoencephalopathy with brainstem and spinal cord involvement and lactate
      elevation: clinical and genetic characterization and target for therapy.
AB  - Leukoencephalopathy with brainstem and spinal cord involvement and lactate
      elevation is a disorder caused by recessive mutations in the gene DARS2, which
      encodes mitochondrial aspartyl-tRNA synthetase. Recent observations indicate that
      the phenotypic range of the disease is much wider than initially thought.
      Currently, no treatment is available. The aims of our study were (i) to explore a
      possible genotype-phenotype correlation; and (ii) to identify potential
      therapeutic agents that modulate the splice site mutations in intron 2 of DARS2,
      present in almost all patients. A cross-sectional observational study was
      performed in 78 patients with two DARS2 mutations in the Amsterdam and Helsinki
      databases up to December 2012. Clinical information was collected via
      questionnaires. An inventory was made of the DARS2 mutations in these patients
      and those previously published. An assay was developed to assess mitochondrial
      aspartyl-tRNA synthetase enzyme activity in cells. Using a fluorescence reporter
      system we screened for drugs that modulate DARS2 splicing. Clinical information
      of 66 patients was obtained. The clinical severity varied from infantile onset,
      rapidly fatal disease to adult onset, slow and mild disease. The most common
      phenotype was characterized by childhood onset and slow neurological
      deterioration. Full wheelchair dependency was rare and usually began in
      adulthood. In total, 60 different DARS2 mutations were identified, 13 of which
      have not been reported before. Except for 4 of 42 cases published by others, all
      patients were compound heterozygous. Ninety-four per cent of the patients had a
      splice site mutation in intron 2. The groups of patients sharing the same two
      mutations were too small for formal assessment of genotype-phenotype correlation.
      However, some combinations of mutations were consistently associated with a mild
      phenotype. The mitochondrial aspartyl-tRNA synthetase activity was strongly
      reduced in patient cells. Among the compounds screened, cantharidin was
      identified as the most potent modulator of DARS2 splicing. In conclusion, the
      phenotypic spectrum of leukoencephalopathy with brainstem and spinal cord
      involvement and lactate elevation is wide, but most often the disease has a
      relatively slow and mild course. The available evidence suggests that the
      genotype influences the phenotype, but because of the high number of private
      mutations, larger numbers of patients are necessary to confirm this. The activity
      of mitochondrial aspartyl-tRNA synthetase is significantly reduced in patient
      cells. A compound screen established a 'proof of principle' that the splice site
      mutation can be influenced. This finding is promising for future therapeutic
      strategies. 

PMID- 24566673
TI  - Pharmacological evaluation for anticancer and immune activities of a novel
      polysaccharide isolated from Boletus speciosus Frost.
AB  - The fungal polysaccharides have been revealed to exhibit a variety of biological
      activities, including antitumor, immune-stimulation and antioxidation activities.
      In the present study, the immune and anticancer activities of a novel
      polysaccharide, BSF-A, isolated from Boletus speciosus Frost was investigated.
      The inhibitory rate of S180 tumors in mice treated with 40 mg/kg BSF-A reached
      62.449%, which was the highest rate from the three doses administered; this may
      be comparable to mannatide. The antitumor activity of BSF-A is commonly
      considered to be a consequence of the stimulation of the cell-mediated immune
      response, as it may significantly promote the macrophage cells in the dose range
      of 100-400 ug/ml in vitro. The levels of the cytokines, IL-6, IL-1beta and TNF
      alpha, and nitric oxide, induced by BSF-A treatment at varying concentrations in
      the macrophage cells were similar to the levels in the cells treated with
      lipopolysaccharide. There was weak expression of the TNF-alpha, IL-6, IL-1beta
      and inducible nitric oxide synthase mRNA in the untreated macrophages, but this
      increased significantly in a dose-dependent manner in the BSF-A-treated cells.
      BSF-A also had a time- and dose-dependent effect on the growth inhibition of the
      Hep-2 cells, with the concentration of 400 ug/ml having the highest inhibitory
      rate. A quantitative PCR array analysis of the gene expression profiles indicated
      that BSF-A had anticancer activities that affected cell apoptosis in the Hep-2
      cells. The results obtained in the present study indicated that the purified
      polysaccharide of Boletus speciosus Frost is a potential source of natural
      anticancer substances.

PMID- 24566674
TI  - Suprasellar pilocytic astrocytoma: one national centre's experience.
AB  - INTRODUCTION: Pilocytic astrocytomas in the supratentorial compartment make up 20
      % of all brain tumours in children with only 5 % of these arising in the
      suprasellar region. Optic pathway gliomas or suprasellar gliomas are often seen
      in neurofibromatosis type 1 (NF1) patients. Given their location, suprasellar
      pilocytic astrocytomas are challenging to manage surgically with high morbidity
      rates from surgical resection. We assess our cohort of patients with suprasellar
      pilocytic astrocytoma and document our experience. METHOD: A retrospective review
      of patients diagnosed with suprasellar glioma between 2000-October 2012. We
      included patients diagnosed with optic pathway glioma based on radiological
      features (with or without biopsy) and those who had a biopsy confirming pilocytic
      astrocytoma. RESULTS: Fifty-three patients included (sporadic tumours 24 and NF1
      related 29). Fifteen sporadic and four NF1 patients were biopsied. Twelve
      sporadic and 13 NF1 patients were initially treated with chemotherapy while only
      1 patient had radiotherapy initially. Progression was noted in 58 % of the
      sporadic group and 24 % of the NF1 group. The only significant factor for
      progression was NF1 status (p = 0.026). CONCLUSION: Management should be guided
      by individual patient circumstance. In our cohort, chemotherapy did not
      significantly improve progression free survival; however, NF1 status
      significantly correlated with the decreased progression.

PMID- 24566675
TI  - Comparison of ultrasound and magnetic resonance imaging in the prenatal diagnosis
      of Apert syndrome: report of a case.
AB  - BACKGROUND: The birth prevalence of Apert syndrome is estimated at 1:64,500 and
      accounts for about 4.5 % of all craniosynostosis with a male/female ratio equal
      to 1:1. It is associated to allelic mutations in the fibroblast growth factor
      receptor 2 (FGFR2) gene. Majority cases are sporadic. Prenatal ultrasound
      diagnosis is based on the detection of abnormal cranial shape, midfacial
      hypoplasia and bilateral syndactyly of hands and feet, hypertelorism, and
      exorbitism. Other abnormalities includes central nervous system anomalies,
      congenital heart diseases, cleft palate, and urogenital diseases. CASE REPORT: A
      37-year-old Caucasian woman, gravida 2, para 1, was referred to our center of
      Prenatal Diagnosis for routine ultrasound at 21 weeks of gestation. We detected
      irregular head shape, dolicocephaly, prominent forehead, bilateral mild
      ventriculomegaly, suspicion of partial agenesis of the corpus callosum,
      hypertelorism, and midfacial hypoplasia, with a depressed nasal bridge and
      syndactyly, prompting a suspicion for Apert syndrome. Magnetic resonance excluded
      agenesis of corpus callosum and confirmed bilateral mild ventriculomegaly. A
      follow-up ultrasound, performed at 23 weeks, confirmed the anomalies showed in
      the previous scan. An amniocentesis was performed. The results showed a normal
      male karyotype, while the molecular genetic test confirmed a mutation in FGFR2
      gene. Fetus macroscopic analysis showed compatible features. CONCLUSIONS: Our
      case underlines the complementary role of ultrasound and magnetic resonance
      imaging in the early prenatal diagnosis of Apert syndrome.

PMID- 24566672
TI  - Disordered amyloidogenic peptides may insert into the membrane and assemble into
      common cyclic structural motifs.
AB  - Aggregation of disordered amyloidogenic peptides into oligomers is the causative
      agent of amyloid-related diseases. In solution, disordered protein states are
      characterized by heterogeneous ensembles. Among these, beta-rich conformers self
      assemble via a conformational selection mechanism to form energetically-favored
      cross-beta structures, regardless of their precise sequences. These disordered
      peptides can also penetrate the membrane, and electrophysiological data indicate
      that they form ion-conducting channels. Based on these and additional data,
      including imaging and molecular dynamics simulations of a range of amyloid
      peptides, Alzheimer's amyloid-beta (Abeta) peptide, its disease-related variants
      with point mutations and N-terminal truncated species, other amyloidogenic
      peptides, as well as a cytolytic peptide and a synthetic gel-forming peptide, we
      suggest that disordered amyloidogenic peptides can also present a common motif in
      the membrane. The motif consists of curved, moon-like beta-rich oligomers
      associated into annular organizations. The motif is favored in the lipid bilayer
      since it permits hydrophobic side chains to face and interact with the membrane
      and the charged/polar residues to face the solvated channel pores. Such channels
      are toxic since their pores allow uncontrolled leakage of ions into/out of the
      cell, destabilizing cellular ionic homeostasis. Here we detail Abeta, whose
      aggregation is associated with Alzheimer's disease (AD) and for which there are
      the most abundant data. AD is a protein misfolding disease characterized by a
      build-up of Abeta peptide as senile plaques, neurodegeneration, and memory loss.
      Excessively produced Abeta peptides may directly induce cellular toxicity, even
      without the involvement of membrane receptors through Abeta peptide-plasma
      membrane interactions. 

PMID- 24566676
TI  - Prevalence of resistant occipital lobe epilepsy associated with celiac disease in
      children.
AB  - PURPOSE: Celiac disease (CD) is a chronic, inflammatory autoimmune disorder
      caused by intolerance to ingested gluten. Increased frequency of CD has been
      reported in occipital lobe epilepsy. The aim of the present study is to
      investigate the frequency of CD among children followed up due to epilepsy and
      diagnosed with epileptic activity in the occipital lobe in at least one
      electroencephalography (EEG) test. METHODS: For this research, 90 pediatric
      epilepsy patients with epileptic activity in the occipital lobe were enrolled in
      the study group, while the control group comprised of 100 healthy children. In
      addition to the EEG examination, tissue transglutaminase (tTG) antibody was
      determined on duodenal biopsy. RESULTS: None of the healthy children in the
      control group was positive in terms of the tTG antibody test used to scan CD. In
      the group with epileptic activity in the occipital lobe, two patients out of 90
      were tTG antibody positive. The seroprevalence was 1/45 (2.22 %) in this group.
      These two patients were diagnosed with CD based on the endoscopic duodenal
      biopsy. In these patients, the seizures were uncontrollable through monotherapy.
      CONCLUSIONS: Our results showed that the prevalence of CD is observed to be
      higher than the normal population among the patients with occipital lobe
      epilepsy. This type of seizure disorder seems to be more resistant to
      monotherapy, compared with other types of occipital epilepsy. Therefore,
      screening for CD is recommended in children with resistant epileptic activity in
      the occipital lobe.

PMID- 24566677
TI  - Acetaminophen use during pregnancy, behavioral problems, and hyperkinetic
      disorders.
AB  - IMPORTANCE: Acetaminophen (paracetamol) is the most commonly used medication for
      pain and fever during pregnancy in many countries. Research data suggest that
      acetaminophen is a hormone disruptor, and abnormal hormonal exposures in
      pregnancy may influence fetal brain development. OBJECTIVE: To evaluate whether
      prenatal exposure to acetaminophen increases the risk for developing attention
      deficit/hyperactivity disorder (ADHD)-like behavioral problems or hyperkinetic
      disorders (HKDs) in children. DESIGN, SETTING, AND PARTICIPANTS: We studied
      64,322 live-born children and mothers enrolled in the Danish National Birth
      Cohort during 1996-2002. EXPOSURES: Acetaminophen use during pregnancy was
      assessed prospectively via 3 computer-assisted telephone interviews during
      pregnancy and 6 months after child birth. MAIN OUTCOMES AND MEASURES: To
      ascertain outcome information we used (1) parental reports of behavioral problems
      in children 7 years of age using the Strengths and Difficulties Questionnaire;
      (2) retrieved HKD diagnoses from the Danish National Hospital Registry or the
      Danish Psychiatric Central Registry prior to 2011; and (3) identified ADHD
      prescriptions (mainly Ritalin) for children from the Danish Prescription
      Registry. We estimated hazard ratios for receiving an HKD diagnosis or using ADHD
      medications and risk ratios for behavioral problems in children after prenatal
      exposure to acetaminophen. RESULTS: More than half of all mothers reported
      acetaminophen use while pregnant. Children whose mothers used acetaminophen
      during pregnancy were at higher risk for receiving a hospital diagnosis of HKD
      (hazard ratio = 1.37; 95% CI, 1.19-1.59), use of ADHD medications (hazard ratio =
      1.29; 95% CI, 1.15-1.44), or having ADHD-like behaviors at age 7 years (risk
      ratio = 1.13; 95% CI, 1.01-1.27). Stronger associations were observed with use in
      more than 1 trimester during pregnancy, and exposure response trends were found
      with increasing frequency of acetaminophen use during gestation for all outcomes
      (ie, HKD diagnosis, ADHD medication use, and ADHD-like behaviors; P trend <
      .001). Results did not appear to be confounded by maternal inflammation,
      infection during pregnancy, the mother's mental health problems, or other
      potential confounders we evaluated. CONCLUSIONS AND RELEVANCE: Maternal
      acetaminophen use during pregnancy is associated with a higher risk for HKDs and
      ADHD-like behaviors in children. Because the exposure and outcome are frequent,
      these results are of public health relevance but further investigations are
      needed.

PMID- 24566678
TI  - A facile mechanophore functionalization of an amphiphilic block copolymer towards
      remote ultrasound and redox dual stimulus responsiveness.
AB  - Two different site-specific cleavage mechanisms for copolymer micelles under
      ultrasound and redox were confirmed. The finding that ultrasound induced
      mechanochemical cleavage of central ester bonds can open up a new way in the
      design of novel ultrasound responsive copolymer micelles for drug release. 

PMID- 24566679
TI  - Genome-wide methylation changes are associated with muscle fiber density and drip
      loss in male three-yellow chickens.
AB  - In eukaryotes, DNA methylation is an important epigenetic modification involved
      in gene expression regulation. Meat quality traits are complicated traits that
      are controlled by many genes. Changes in the methylation levels of certain genes
      controlling meat quality traits will inevitably affect their expression levels,
      thereby affecting meat quality. The objectives of this study were to investigate
      the differences in the DNA methylation level in pectoral muscle tissues using
      fluorescent-labeled methylation sensitive amplified polymorphism and their
      relationships with meat quality traits in three-yellow chickens. The results
      showed that the differences in the DNA methylation level had a highly significant
      effect on muscle fiber density and drip loss (P<0.01). However, no significant
      correlations were found between the DNA methylation levels and the other
      investigated traits (P>0.05).

PMID- 24566680
TI  - Molecular cloning and expression analysis of inhibitor of growth protein 3 (ING3)
      in the Manila clam, Ruditapes philippinarum.
AB  - Inhibitor of growth protein 3 (ING3), a new member of ING family, is involved in
      the regulation of various processes. In this study, a full-length cDNA of ING3
      (named as RpING3) was cloned from the gill of Ruditapes philippinarum by rapid
      amplification of cDNA ends method for the first time. The cDNA obtained was 1442
      bp exclusive of poly (A) residues with a 1248 bp open reading frame encoding 415
      amino acids. The RpING3 protein has a calculated molecular weight of 46.59 kDa
      and isoelectric point of 6.62. Two conserved motif and some functional sites were
      found. Tissue distribution analysis of the RpING3 mRNA revealed that the RpING3
      expression level was much higher in gill and digestive gland while lower in
      mantle, foot and adductor muscle. The temporal expression of RpING3 in digestive
      gland after lead exposure was recorded by quantitative real-time PCR. The result
      showed that RpING3 was rapidly up-regulated at 6 h post-exposure and reached
      tenfold of the control group. These results suggest that RpING3 dependent
      signaling pathway is present in Manila clam and RpING3 may play important roles
      in protecting cells from heavy metal damage in R. philippinarum.

PMID- 24566681
TI  - Role of RASSF1A promoter methylation in the pathogenesis of hepatocellular
      carcinoma: a meta-analysis of 21 cohort studies.
AB  - We carried out the current meta-analysis aiming to comprehensively assess the
      potential role of RASSF1A aberrant promoter methylation in the pathogenesis of
      hepatocellular carcinoma (HCC). A range of electronic databases were searched:
      Web of Science (1945-2013), the Cochrane Library Database (Issue 12, 2013),
      PubMed (1966-2013), EMBASE (1980-2013), CINAHL (1982-2013) and the Chinese
      Biomedical Database (CBM) (1982-2013) without language restrictions. Meta
      analysis was conducted using the STATA 12.0 software. Crude risk difference (RD)
      with their 95% confidence interval (95% CI) was calculated. In the present meta
      analysis, 21 clinical cohort studies with a total of 1,205 HCC patients were
      included. The results of our meta-analysis illustrated that the frequency of
      RASSF1A promoter methylation in cancer tissues were significantly higher than
      those of normal, adjacent and benign tissues (cancer tissues vs. normal tissues:
      RD = 0.63, 95% CI 0.53-0.73, P < 0.001; cancer tissues vs. adjacent tissues: RD =
      0.43, 95% CI 0.33-0.53, P < 0.001; cancer tissues vs. benign tissues: RD = 0.48,
      95% CI 038-0.58, P < 0.001; respectively). Further subgroup by ethnicity
      demonstrated that RASSF1A aberrant promoter methylation was correlated with the
      pathogenesis of HCC among both Asians and Caucasians (all P < 0.05). The current
      meta-analysis suggests that RASSF1A aberrant promoter methylation may be
      implicated in the pathogenesis of HCC. Thus, detection of RASSF1A promoter
      methylation may be a helpful and valuable biomarker for diagnosis and prognosis
      of HCC.

PMID- 24566682
TI  - Studies on the role of neutralizing antibodies against envelope genes in
      resolving HCV pseudo-particles infection.
AB  - Characterization of antibodies targeting the attachment and entry of the viral
      particles into host cells is important for studding antibody mediated
      neutralization. Antibodies against the envelope glycoproteins (EGP) have
      neutralizing capacity and can prevent HCV infections. System based on HCV pseudo
      typed-particles (HCVpp) stably expressing EGP can be used for screening of HCV
      anti envelope neutralizing antibodies in the serum of patients with acute and
      chronic HCV infections. The aim of the current study was to check HCVpp as a
      useful tool for the detection of anti-HCV envelope antibodies in the serum of HCV
      infected patients and to test the binding potential of these antiviral molecules
      to EGP of HCV 3a. Previously developed HCVpp harboring unmodified glycoproteins
      from local isolates in 293T cell line were used in this study. HCVpp were pre
      incubated with different concentrations of anti E1 antibody and different E2
      antibodies to check antiviral activity. Further we used serum samples with
      low/medium (<=800,000 IU/mL), and high (>800,000 IU/mL) viral titer from chronic
      HCV male and female patients. Infection was done in Huh-7 cells for 1 h at 37 oC.
      Infectivity was checked through Luciferase assay. Considerable decrease in HCVpp
      infectivity with anti-envelope antibodies was observed in dose dependent manner.
      Maximum inhibition was seen when 5 ug/ml of monoclonal anti E1 antibody used.
      Further increase in concentration exhibited no decrease in infectivity which
      suggests that other factors are also involved in causing infection. Various well
      characterized E2-specific monoclonal antibodies (mAbs) have been screened for
      their capability to reduce infection in Huh-7 cells. Three of the four mAbs
      specific for the E2 had no effect on the infectivity of HCVpp. Confirmation
      sensitive antibody H53 showed maximum inhibition of infectivity. HCV ELISA
      positive samples from both male and female patients were used to neutralize the
      HCVpp. The neutralizing antibody response was observed in both males and females
      patients and do not assemble the rapidly evolving HCV envelope glycoproteins.
      That is why in spite the presence of neutralizing antibodies in the blood they
      fail to resolve infections. Moreover E1 antibodies insignificantly (>0.05)
      inhibit HCVpp infectivity while E2 antibodies significantly (<0.05) inhibit HCVpp
      infection. Based on the results of this study it is concluded that anti-envelope
      antibodies particularly the anti-E2 could be extremely valuable for
      characterizing the humoral immune response to HCV and for evaluating the
      potential for developing passive and active immunization for hepatitis C along
      with interferon therapy.

PMID- 24566683
TI  - Associations of polymorphisms in GHRL, GHSR, and IGF1R genes with feed efficiency
      in chickens.
AB  - The ghrelin (GHRL), ghrelin receptor (GHSR), and insulin-like growth factor 1
      receptor (IGF1R) genes have crucial effects on body weight (BW), body weight gain
      (BWG), feed intake (FI), and feed conversion ratio (FCR) in many species.
      However, few studies on associations of GHRL, GHSR, and IGF1R with BWG, FI, and
      FCR have been reported in chickens. In this study, 16 SNPs in GHRL, GHSR, and
      IGF1R genes were genotyped by matrix-assisted laser desorption/ionization time-of
      flight mass spectrometry (MALDI-TOF MS). The objective of this study was to
      examine the associations of GHRL, GHSR, and IGF1R genes polymorphisms with BW at
      49 days (BW49) and 70 days (BW70) of age, BWG, FI, and FCR in the interval in two
      yellow meat-type populations with a total of 724 birds. The results showed that
      rs15675067 of GHRL was significantly associated with BW70, BWG, and FCR (P <
      0.05). For GHSR, rs16675844 had significant effects on FI and FCR (P < 0.01), and
      that rs14678932 showed significant association with BWG and FI (P < 0.05).
      Rs14011780 of IGF1R was strongly associated with BW49, BW70, and FCR (P < 0.05).
      Furthermore, haplotypes based on three SNPs of rs14986828, rs15675067, and
      rs15675065 in GHRL were significantly associated with BW70 and FCR (P < 0.05).
      Meanwhile, a three-SNP haplotype comprising rs14011783, rs14011780, and
      rs14011776 in IGF1R showed significant effects on BW49, BW70, and FCR (P < 0.05).
      Therefore, it was concluded that the identified SNPs and analyzed haplotypes in
      this study might be useful for broiler breeding programs.

PMID- 24566684
TI  - Aberrant promoter methylation of RASSF1A gene may be correlated with colorectal
      carcinogenesis: a meta-analysis.
AB  - We conducted a meta-analysis of cohort studies to evaluate the potential role of
      RASSF1A promoter methylation in colorectal carcinogenesis. A range of electronic
      databases were searched: PubMed (1966-2013), the Cochrane Library Database (Issue
      12, 2013), EMBASE (1980-2013), CINAHL (1982-2013), Web of Science (1945-2013) and
      the Chinese Biomedical Database (CBM) (1982-2013) without language restrictions.
      Meta-analysis was conducted using the STATA 12.0 software. Crude odds ratio (OR)
      with 95% confidence interval (95% CI) was calculated. Eleven clinical cohort
      studies with a total of 1,505 colorectal cancer (CRC) patients that met all
      inclusion criteria were included in our meta-analysis. The results of our meta
      analysis revealed that the frequency of RASSF1A promoter methylation was strongly
      correlated with clinical stage (OR = 1.69, 95% CI 1.16-2.44, P = 0.006),
      histological grade (OR = 1.92, 95% CI 1.22-3.04, P = 0.005) and distant
      metastasis (OR = 2.59, 95% CI 1.46-4.60, P = 0.037) of CRC patients. However, we
      observed no positive correlations of RASSF1A promoter methylation with gender (OR
      = 1.04, 95% CI 0.74-1.46, P = 0.842), age (OR = 1.70, 95% CI 0.98-2.93, P =
      0.057) and lymph node metastasis (OR = 1.65, 95% CI 0.87-3.14, P = 0.127) of CRC
      patients. Further subgroup analysis by ethnicity demonstrated that RASSF1A
      promoter methylation was correlated with clinicopathological characteristics of
      CRC patients among Asians (clinical stage: OR = 2.55, 95% CI 1.55-4.20, P <
      0.001; histological grade: OR = 2.70, 95% CI 1.44-5.06, P = 0.002; lymph node
      metastasis: OR = 4.09, 95% CI 1.49-11.26, P = 0.006; distant metastasis: OR =
      5.38, 95% CI 1.73-16.70, P = 0.004), but not among Caucasians and Africans (all P
      > 0.05). Our meta-analysis has shown positive correlations between aberrant
      promoter methylation of RASSF1A gene and clinicopathological characteristics of
      CRC patients, especially among Asians.

PMID- 24566685
TI  - Regulatory effect of AMP-activated protein kinase on pulmonary hypertension
      induced by chronic hypoxia in rats: in vivo and in vitro studies.
AB  - Activation of AMP-activated protein kinase (AMPK) plays an important role in
      cardiovascular protection. It can inhibit arterial smooth muscle cell
      proliferation and cardiac fibroblast collagen synthesis induced by anoxia.
      However, the role of AMPK-dependent signalling cascades in the pulmonary vascular
      system is currently unknown. This study aims to determine the effects of AMPK on
      pulmonary hypertension and pulmonary vessel remodelling induced by hypoxia in
      rats using in vivo and in vitro studies. In vivo study: pulmonary hypertension,
      right ventricular hypertrophy and pulmonary vascular remodelling were found in
      hypoxic rats. Meanwhile, AMPKalpha1 and phosphorylated AMPKalpha1 were increased
      markedly in pulmonary arterioles and lung tissues. Mean pulmonary arterial
      pressure, index of right ventricular hypertrophy and parameters of pulmonary
      vascular remodelling, including vessel wall area/total area, density of nuclei in
      medial smooth muscle cells, and thickness of the medial smooth muscle cell layer
      were markedly suppressed by AICAR, an AMPK agonist. In vitro study: the
      expression of AMPKalpha1 and phosphorylated AMPKalpha1 was increased in pulmonary
      artery smooth muscle cells (PASMCs) under hypoxic conditions. The effects of
      PASMC proliferation stimulated by hypoxia were reinforced by treatment with
      Compound C, an AMPK inhibitor. AICAR inhibited the proliferation of PASMCs
      stimulated by hypoxia. These findings suggest that AMPK is involved in the
      formation of hypoxia-induced pulmonary hypertension and pulmonary vessel
      remodelling. Up-regulating AMPK can contribute to decreasing pulmonary vessel
      remodelling and pulmonary hypertension induced by hypoxia. 

PMID- 24566686
TI  - Human leukocyte antigen (HLA)-C polymorphisms are associated with a decreased
      risk of rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is an autoimmune rheumatological disease thought to
      have substantial genetic contributions. Several genetic factors involved in the
      susceptibility to psoriasis and psoriatic arthritis (PsA) have been identified
      with genome-wide association studies, including human leukocyte antigen (HLA)-C,
      junction adhesion molecule 2 (JAM2) and REL. Psoriasis and PsA may share many
      features in common with RA. We hypothesized that this polymorphism may contribute
      to RA susceptibility in a Chinese population. We studied HLA-C rs10484554 C/T,
      HLA-C rs12212594 T/C, HLA-C rs12191877 C/T, JAM2 rs2829866 A/T and REL rs702873
      G/A polymorphisms in 520 patients with RA and 520 controls in a Chinese
      population. HLA-C rs12191877 C/T polymorphism was in complete linkage
      disequilibrium (LD) (D' = 1.0, r (2) = 1.0) with HLA-C rs10484554 C/T
      polymorphism. When the HLA-C rs10484554 CC homozygote genotype was used as the
      reference group, the TT/CT genotypes were associated with a significantly
      decreased risk for RA (adjusted OR = 0.72, 95% CI = 0.52-0.99, p = 0.044). We
      found that the HLA-C rs12191877 C/T polymorphism was also associated with a
      decreased risk of RA. HLA-C rs12212594 T/C, JAM2 rs2829866 A/T and REL rs702873
      G/A polymorphisms were not associated with the risk of RA. These results provide
      evidence that HLA-C polymorphisms are associated with a decreased risk of RA.

PMID- 24566687
TI  - Gene structure and identification of minimal promoter of Pou2 expressed in
      spermatogonial cells of rohu carp, Labeo rohita.
AB  - Mammalian Pou5f1 is a known transcriptional regulator involving maintenance of
      embryonic and spermatogonial stem cells. Little is known about teleost Pou2, an
      ortholog of mammalian Pou5f1. Evidences of discrepancy in expression pattern
      between fish species were documented. To better understand, we have cloned and
      characterized Pou2 gene of farmed rohu carp, Labeo rohita. It contained five
      exons with an open reading frame of 1419 bp long, translatable to 472 aa. A
      bipartite DNA binding domain termed POU domain, comprising of POU-specific and
      POU-homeo sub-domains, was identified. Rohu Pou2 is highly conserved with
      zebrafish counterpart, as evidenced by 92% overall sequence identity of deduced
      protein. The POU domain remained highly conserved (showing more than 90%
      identities) within fish species. Even though there is a divergence between Pou2
      and Pou5f1, the common POU-specific domain remained conserved throughout
      eukaryotes indicating their possible involvements in common trans-activation
      pathway(s) between mammals and non-mammals. In support, we have provided evidence
      that Pou2 is indeed abundantly expressed in proliferating rohu spermatogonial
      cells and hence participates in stem cell maintenance. Its mRNA accumulation in
      the ovary supported about its maternal transmission with possible regulatory
      roles during embryogenesis. The 5'-flanking region (~2.7 kb) of rohu Pou2 was
      sequenced and computational analysis detected several putative regulatory
      elements. These elements have been conserved among fish species analysed.
      Luciferase assay identified a mammalian-type 'TATA-less promoter' capable of
      driving Pou2 gene transcription. These findings will help for future studies in
      elucidating participatory role of fish Pou2 in male germ cell development.

PMID- 24566688
TI  - Deletion of late cornified envelope genes, LCE3C_LCE3B-del, is not associated
      with psoriatic arthritis in Tunisian patients.
AB  - A deletion of two genes from the late cornified envelope (LCE), LCE3B and LCE3C
      within epidermal differentiation complex on chromosome 1 was shown to be
      associated with both psoriasis and psoriatic arthritis (PsA) in several
      populations. To assess whether this deletion may contribute to the genetic
      predisposition to PsA in Tunisia, a total of 73 patients with PsA and 120 healthy
      matched controls were screened for the deletion, LCE3C_LCE3B-del, and its tag
      SNP, rs4112788. We also evaluated a possible relationship between PSORS1 and
      LCE3C_LCE3B-del through genotyping two proxy markers to HLA-C (rs12191877 and
      rs2073048). Our results did not provide evidence for association between the
      LCE3C_LCE3B-del nor the rs4112788 and the PsA. Similarly, no significant
      epistatic effect was observed. Our data suggest that The LCE deletion, previously
      identified in patients with psoriasis, is not of a major importance in the
      development of PsA in Tunisian patients supporting the current perception that
      different genetic risk factors contribute to skin and joint disease. However,
      these results need to be confirmed by additional large-scale studies of Tunisian
      PsA patients and controls. 

PMID- 24566689
TI  - The over-expression of Chrysanthemum crassum CcSOS1 improves the salinity
      tolerance of chrysanthemum.
AB  - Soil salinity represents a major constraint on plant growth. Here, we report that
      the over-expression of the Chrysanthemum crassum plasma membrane Na(+)/H(+)
      antiporter gene CcSOS1, driven by the CaMV 35S promoter, improved the salinity
      tolerance of chrysanthemum 'Jinba'. In salinity-stressed transgenic plants, both
      the proportion of the leaf area suffering damage and the electrical conductivity
      of the leaf were lower in the transgenic lines than in salinity-stressed wild
      type plants. After a 6 day exposure to 200 mM NaCl, the leaf content of both
      chlorophyll (a+b) and proline was higher in the transgenic than in the wild type
      plants. The activity of both superoxide dismutase and peroxidase was higher in
      the transgenic than in the wild type plants throughout the period of NaCl stress.
      The transgenic plants had a stronger control over the ingress of Na(+) into the
      plant, particularly with respect to the youngest leaves, and so maintained a more
      favorable K(+)/Na(+) ratio. The result suggests that a possible strategy for
      improving the salinity tolerance of chrysanthemum could target the restriction of
      Na(+) accumulation. This study is the first to report the transgenic expression
      of a Na(+) efflux carrier in chrysanthemum.

PMID- 24566690
TI  - GSTP1 Ile105Val polymorphism is associated with lung cancer risk among Asian
      population and smokers: an updated meta-analysis.
AB  - Many studies have examined the association between the GSTP1 Ile105Val (rs 1695)
      gene polymorphism and lung cancer risk in various populations, but their results
      have been inconsistent. To assess this relationship more precisely, a meta
      analysis was performed. The PubMed and CNKI database was searched for case
      control studies published up to July 2012. Data were extracted and pooled odds
      ratios (OR) with 95% confidence intervals (CI) were calculated. Ultimately, 42
      studies, comprising 12,304 lung cancer cases and 15,729 controls were included.
      Overall, for G allele carriers (GA + GG) versus homozygote AA, the pooled OR was
      1.05 (95% CI 0.99-1.10 P = 0.092 for heterogeneity), for GG versus AA the pooled
      OR was 1.04 (95% CI 0.96-1.12 P = 0.084 for heterogeneity). In the stratified
      analysis by ethnicity, gender, histological types of lung cancer and smoking
      status, a significant association was found in Asians and smokers, not in
      Caucasian or mixed population, Male, Female population, lung AC, SCC, SCLC or non
      smokers. Publication bias was found by using the funnel plot and Egger's test.
      Overall, there is no evidence showing a significant correlation between GSTP1
      Ile105Val gene polymorphism and lung cancer risk in overall population, however
      stratified analysis by ethnicity, histology, gender and smoking status, it
      correlate with increased lung cancer susceptibility among Asians and smokers.

PMID- 24566691
TI  - Protective effect of ellagic acid against TCDD-induced renal oxidative stress:
      modulation of CYP1A1 activity and antioxidant defense mechanisms.
AB  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) belongs to toxicologically important
      class of poly halogenated aromatic hydrocarbons and produce wide variety of
      adverse effects in humans. The present study investigated the protective effect
      of ellagic acid, a natural polyphenolic compound against TCDD-induced
      nephrotoxicity in Wistar rats. TCDD-induced nephrotoxicity was reflected in
      marked changes in the histology of kidney, increase in levels of kidney markers
      (serum urea, serum creatinine) and lipid peroxides. A significant increase in
      activity of phase I enzyme CYP1A1 with concomitant decline in the activities of
      phase II enzymes [non-enzymic antioxidant and various enzymic antioxidants such
      as superoxide dismutase, catalase, glutathione peroxidase, glutathione-s
      transferase] was also observed. In addition, TCDD treated rats showed alterations
      in ATPase enzyme activities such as Na(+) K(+)-ATPase, Mg(2+) ATPase and Ca(2+)
      ATPase. Oral pre-treatment with ellagic acid prevented TCDD-induced alterations
      in levels of kidney markers. Ellagic acid pre-treatment significantly
      counteracted TCDD-induced oxidative stress by decreasing CYP1A1 activity and
      enhancing the antioxidant status. Furthermore, ellagic acid restored TCDD-induced
      histopathological changes and alterations in ATPase enzyme activities. The
      results of the present study show that significant protective effect rendered by
      ellagic acid against TCDD-induced nephrotoxicity might be attributed to its
      antioxidant potential. 

PMID- 24566694
TI  - [Editor's commentary. Rare diseases in Hungary].

PMID- 24566692
TI  - Isolation, classification and transcription profiles of the AP2/ERF transcription
      factor superfamily in citrus.
AB  - The AP2/ERF gene family encodes plant-specific transcription factors. In model
      plants, AP2/ERF genes have been shown to be expressed in response to
      developmental and environmental stimuli, and many function downstream of the
      ethylene, biotic, and abiotic stress signaling pathways. In citrus, ethylene is
      effective in regulation citrus fruit quality, such as degreening and aroma.
      However, information about the citrus AP2/ERF family is limited, and would
      enhance our understanding of fruit responses to environmental stress, fruit
      development and quality. CitAP2/ERF genes were isolated using the citrus genome
      database, and their expression patterns analyzed by real-time PCR using various
      orange organs and samples from a fruit developmental series. 126 sequences with
      homologies to AP2/ERF proteins were identified from the citrus genome, and, on
      the basis of their structure and sequence, assigned to the ERF family (102), AP2
      family (18), RAV family (4) and Soloist (2). MEME motif analysis predicted the
      defining AP2/ERF domain and EAR repressor domains. Analysis of transcript
      accumulation in Citrus sinensis cv. 'Newhall' indicated that CitAP2/ERF genes
      show organ-specific and temporal expression, and provided a framework for
      understanding the transcriptional regulatory roles of AP2/ERF gene family members
      in citrus. Hierarchical cluster analysis and t tests identified regulators that
      potentially function during orange fruit growth and development. 

PMID- 24566693
TI  - Molecular characterization of cotton C-repeat/dehydration-responsive element
      binding factor genes that are involved in response to cold stress.
AB  - Low temperature, drought and salinity are major abiotic stresses that influence
      survival, productivity and geographical distribution of many important crops
      across the globe. The C-repeat/dehydration-responsive element binding
      transcription factors (CBF/DREB) are important proteins involved in response to
      abiotic stresses in plants. In this study, twenty-one CBF genes were identified
      in cotton (Gossypium hirsutum) by bioinformatic approach. The twenty-one CBF
      genes (named as GhCBF1--GhCBF21) were characterized to encode proteins that share
      high similarity with those plant cold stress-related CBF proteins, which contain
      the classic AP2 domain of 58 amino acid residues. Phylogenetic analysis revealed
      that the isolated cotton CBF genes can be classified into 4 groups: GhCBF I,
      GhCBF II, GhCBF III and GhCBF IV. RT-PCR analysis indicated that GhCBF genes were
      up-regulated in cotton plants under cold stress. Furthermore, four GhCBF genes
      were up-regulated in cotton under salinity and drought treatments. Our data
      provided valuable information for further exploring the roles of the CBF genes in
      cotton development and in response to cold stress.

PMID- 24566695
TI  - [Hungarian national plan and strategy for rare diseases].
AB  - The rarity of low prevalence diseases and the lack of information, research,
      diagnosis, treatment and expert availability may mean that the people affected do
      not benefit from the health resources and services they need. Rare diseases are
      considered to have little impact on society as a whole, yet they pose serious
      difficulties for sufferers and their families. By the end of the last century,
      two robust achievements in science and technology, i.e. the biotechnological and
      informatics revolutions, have created a real base for global approach to rare
      diseases by coordinating the capacities for health care, biomedical research and
      drug development and pooling the very limited resources available both nationally
      and transnationally. The European Commission has taken a number of actions which
      help patients and professionals to share expertise and information across borders
      with the objective of reducing the number of people suffering from these types of
      diseases. These actions together form the legal basis of the European Union
      policy on rare diseases. Orphan or rare diseases are now one of the priorities in
      the public health programmes in European Union. In 2009, the document "European
      Union Council Recommendation on an action in the field of rare diseases" was
      released with the main goal to provide national health authorities with
      supporting tools for the development and implementation of national plans and
      strategies for rare diseases by the end of 2013. This recommendation adopted by
      European Union Member States, allows common policy guidelines to be shared
      everywhere in Europe. By September 2013 the Hungarian National Plan for Rare
      Diseases, a health policy strategy until 2020 was finalized. The present report
      gives a short view on the document.

PMID- 24566696
TI  - [Rare diseases and their patient organization: the Hungarian Federation of People
      with Rare and Congenital Diseases].
AB  - The aim of the author is to discuss special issues of rare diseases, with
      emphasis on circumstances present in Hungary, including those leading to the
      foundation of the non-governmental organization, the Hungarian Federation of
      People with Rare and Congenital Diseases. The author briefly reviews the most
      important findings of current international surveys which have been performed
      with or without the involvement of member associations of the Hungarian
      Federation of People with Rare and Congenital Diseases. At the level of medical
      and social services in Hungary, it is still "incidental" to get to the
      appropriate expert or centre providing the diagnosis or treatment. It is
      difficult to find the still very few existing services due to the lack of
      suitable "pathways" and referrals. There are long delays in obtaining the first
      appointment, resulting in vulnerability and inequality along the regions. The
      overall consequence is the insufficiency or lack of access to medical and social
      services. There are also difficulties related to the supply of orphan medication
      and the long duration of hospitalization. At the level of patient organizations
      financial scarcity and uncertainty are typical, combined with inappropriate
      infrastructural background and human resources. The poor quality of organization
      of patient bodies along with insufficient cooperation among them are
      characteristic as well. The author concludes that a National Plan or Strategy is
      needed to improve the current fragmentation of services which would enable
      patients and health, social and educational professionals to provide and use the
      best care in the practice. This would ensure all patients with rare diseases to
      be diagnosed within a possible shortest time allowing access to the care and
      support needed in time resulting in a decrease in burden of families and society.

PMID- 24566697
TI  - [Adult-onset rare diseases].
AB  - The present paper is focusing on rare diseases manifesting in late childhood or
      adulthood. A part of these syndromes are not of genetic origin, such as
      relatively or absolutely rare infections, autoimmune diseases, tumours, or
      diseases due to rare environmental toxic agents. In addition, even a large
      proportion of genetic disorders may develop in adulthood or may have adult forms
      as well, affecting are almost each medical specialization. Examples are storage
      disorders (e.g. adult form of Tay-Sachs disease, Gaucher-disease), enzyme
      deficiencies (e.g. ornithin-transcarbamylase deficiency of the urea cycle
      disorders), rare thrombophilias (e.g. homozygous factor V. Leiden mutation,
      antithrombin deficiency), or some rare monogenic disorders such as Huntington
      chorea and many others. It is now generally accepted that at least half of the 6
      8000 "rare diseases" belong either to the scope of adult-care (e.g. internal
      medicine, neurology), or to "age-neutral" specialities such as ophtalmology,
      dermatology etc.).

PMID- 24566698
TI  - [Clinical and genetic characteristics of craniosynostosis].
AB  - Craniosynostosis is caused by premature fusion of one or more cranial sutures
      leading to deformity of the cranium. Depending on the type and number of the
      sutures involved and the order of their fusion, different forms of deformities
      may develop. Two main types of craniosynostosis can be distinguished: non
      syndromic (isolated) and syndromic forms. In the latter group the cranial
      deformity is usually associated with dysmorphic features, limb anomalies and
      other symptoms while in non-syndromic form the cranial deformity can be seen
      only. The type and severity of associated anomalies in the syndromic form are
      different. Early fusion of sutures can be caused by both environmental and
      genetic factors. In the present paper the authors aim to review the clinical
      features and genetic background of craniosynostosis focusing on some common
      syndromes.

PMID- 24566699
TI  - [Results of clinical and genetic diagnosis of rare diseases in the Eastern region
      of Hungary (2007-2013)].
AB  - INTRODUCTION: 80% of rare diseases have a genetic origin, and 50% manifest
      themselves as congenital anomalies. Their adequate health care includes early
      recognition of genetic anomalies and prevention of recurrence. AIM: The aims of
      the authors were to provide correct diagnoses to patients with multiple
      congenital anomalies with or without mental retardation attending to the
      outpatient clinic of the Clinical Genetics Center at the University of Debrecen
      in the time interval between August 1, 2007 and March 31, 2013, establish the
      possibility of prenatal diagnosis, assess the distribution of different genetic
      mechanisms in the background of rare genetic diseases, compare them with
      international data, and develop an algorithm for the diagnostic approach of rare
      genetic diseases applicable in Hungary. METHOD: Clinical data and genetic results
      of patients were evaluated, and patients were categorized into one of the ten
      proposed etiological groups, based on which the distribution of genetic causes
      was defined. RESULTS: Clinical diagnosis was achieved in 64.3% of patients,
      confirmed genetic diagnosis in 37.8%, while 35.7% of patients remained
      undiagnosed. Several dysmorphic syndromes and metabolic disorders were first
      diagnosed in Hungary, two of which unique in the literature. CONCLUSIONS: In the
      centre of the authors the diagnostic effectiveness of chromosome aberrations
      exceeds the international standards, that of known microdeletions and dysmorphic
      syndromes meets international data, and the genetic diagnosis of mendelian
      disorders and submicroscopic copy number changes remain below international
      figures.

PMID- 24566700
TI  - [Identifying rare genomic disorders with array comparative genomic hybridization
      in Hungary].
AB  - INTRODUCTION: In the past decade the study of genomic disorders has received more
      interest. Array comparative genome hybridization is a widely spread diagnostic
      method in the research of genomic disorders. This method was implemented in the
      laboratory of the authors in 2012. AIM: This molecular cytogenetic method was
      first used to examine patients with complex developmental disorders in whom no
      genetic background was identified by traditional methods. METHOD: The authors
      complemented traditional diagnostic methods with array comparative genome
      hybridization, which has not been used in routine diagnostics in Hungary so far.
      RESULTS: Using this novel method the authors were able to identify genomic
      alterations in 7 out of 18 patients with complex developmental disorders. They
      found de novo alterations in 6 out of 7 patients, which were most likely
      causative in the development of the phenotype, while in one case they detected a
      familial genomic alteration. This method helped the authors to determine the
      breakpoint of genomic variation in their patients and delineate the affected
      genes contributing to the phenotype. CONCLUSIONS: These results call attention to
      the usefulness of next generation diagnostic methods available in the laboratory
      of the authors.

PMID- 24566701
TI  - [Deletion 15q26 syndrome].
AB  - The association of short stature, microcephaly, congenital cardiac anomaly and
      intellectual deficit should always raise the suspicion of chromosomal etiology.
      If G-banded karyotyping fails to detect large chromosomal aberrations, array
      comparative genomic hybridization (array CGH) should be performed to screen for
      submicroscopic pathological copy number changes. The authors present a six-year
      old girl whose symptoms arose from a 4.1 Mb loss in the 15q26.2-26.3 telomeric
      region. The syndrome is characterized by a resistance to the insulin-like growth
      factor 1 - in our case the increased level of the insulin-like growth factor 1
      together with the persistent longitudinal growth failure was an important finding
      and differential diagnostic feature. A brief overview of the literature is
      provided.

PMID- 24566702
TI  - Examining variations in hospital productivity in the English NHS.
AB  - OBJECTIVES: Numerous papers have measured hospital efficiency, mainly using a
      technique known as data envelopment analysis (DEA). A shortcoming of this
      technique is that the number of outputs for each hospital generally outstrips the
      number of hospitals. In this paper, we propose an alternative approach, involving
      the use of explicit weights to combine diverse outputs into a single index,
      thereby avoiding the need for DEA. METHODS: Hospital productivity is measured as
      the ratio of outputs to inputs. Outputs capture quantity and quality of care for
      hospital patients; inputs include staff, equipment, and capital resources applied
      to patient care. Ordinary least squares regression is used to analyse why output
      and productivity varies between hospitals. We assess whether results are
      sensitive to consideration of quality. RESULTS: Hospital productivity varies
      substantially across hospitals but is highly correlated year on year. Allowing
      for quality has little impact on relative productivity. We find that productivity
      is lower in hospitals with greater financial autonomy, and where a large
      proportion of income derives from education, research and development, and
      training activities. Hospitals treating greater proportions of children or
      elderly patients also tend to be less productive. CONCLUSIONS: We have set out a
      means of assessing hospital productivity that captures their multiple outputs and
      inputs. We find substantial variation in productivity among English hospitals,
      suggesting scope for productivity improvement.

PMID- 24566703
TI  - Financial catastrophe and poverty impacts of out-of-pocket health payments in
      Turkey.
AB  - OBJECTIVE: To determine the prevalence of catastrophic health payments, examine
      the determinants of catastrophic expenditures, and assess the poverty impact of
      out-of-pocket (OOP) payments. METHODS: Data came from the 2004 to 2010 Household
      Budget Survey. Catastrophic health spending was defined by health payments as
      percentage of household consumption expenditures and capacity to pay at a set of
      thresholds. The poverty impact was evaluated by poverty head counts and poverty
      gaps before and after OOP health payments. RESULTS: The percentage of households
      that catastrophically spent their consumption expenditure and capacity to pay
      increased from 2004 to 2010, regardless of the threshold used. Households with a
      share of more than 40% health spending in both consumption expenditure and
      capacity to pay accounted for less than 1% across years. However, when a series
      of potential confounders were taken into account, the study found statistically
      significantly increased risk for the lowest threshold and decreased risk for the
      highest threshold in 2010 relative to the base year. Household income, size,
      education, senior and under 5-year-old members, health insurance, disabled
      members, payment for inpatient care and settlement were also statistically
      significant predictors of catastrophic health spending. Overall, poverty head
      counts were below 1%. Poverty gaps reached a maximum of 0.098%, with an overall
      increase in 2010 compared to 2004. CONCLUSIONS: Catastrophe and poverty increased
      from 2004 to 2010. However, given that the realization of some recent policies
      will affect the financial burden of OOP payments on households, the findings of
      this study need to be replicated.

PMID- 24566705
TI  - A phase II study of pralatrexate with vitamin B12 and folic acid supplementation
      for previously treated recurrent and/or metastatic head and neck squamous cell
      cancer.
AB  - BACKGROUND: Pralatrexate (Fotolyn(TM); Allos Therapeutics Inc.) is an antifolate
      dihydrofolate reductase (DHFR) inhibitor. We conducted a phase II study of
      pralatrexate with folic acid and B12 supplementation in patients with recurrent
      and/or metastatic head and neck squamous cell cancer (R/M HNSCC). PATIENTS AND
      METHODS: This was a single-arm, Simon optimal two stage phase II study. Patients
      with R/M HNSCC previously treated with chemotherapy were eligible. The study was
      initiated with a dosing schedule of pralatrexate 190 mg/m(2) biweekly on a 4-week
      cycle with vitamin supplementation. Due to toxicity concerns, the dosing was
      modified to 30 mg/m(2) weekly for 3 weeks in a 4-week cycle with vitamin
      supplementation. Radiologic imaging was to be obtained about every 2 cycles.
      RESULTS: Thirteen subjects were enrolled; 12 were treated. Seven of the twelve
      patients had previously received >=2 lines of chemotherapy. The most common grade
      3 toxicity was mucositis (3 patients). Seven patients did not complete two cycles
      of therapy due to progression of disease (4), toxicity (1), death (1), and
      withdrawal of consent (1). Two deaths occurred: one due to disease progression
      and the other was an unwitnessed event that was possibly related to pralatrexate.
      No clinical activity was observed. The median overall survival was 3.1 months.
      The study was closed early due to lack of efficacy. CONCLUSIONS: Pralatrexate
      does not possess clinical activity against previously treated R/M HNSCC.
      Evaluation of pralatrexate in other clinical settings of HNSCC management with
      special considerations for drug toxicity may be warranted.

PMID- 24566707
TI  - Cost saving associated with implementing a stepwise approach to HLA typing of
      related donors before hematopoietic SCT.

PMID- 24566706
TI  - PF-03446962, a fully-human monoclonal antibody against transforming growth-factor
      beta (TGFbeta) receptor ALK1, in pre-treated patients with urothelial cancer: an
      open label, single-group, phase 2 trial.
AB  - Despite a compelling preclinical rationale for the use of anti-angiogenic drugs
      in urothelial cancer (UC), short-living responses have been observed in clinical
      trials. PF-03446962 is a novel monoclonal antibody against Activin Receptor-Like
      Kinase-1 (ALK1), a type I subclass of the TGFbeta receptor, with dose-dependent
      anti-angiogenic activity. An open label, single-group, phase 2 trial of PF
      03446962 was conducted in salvage setting. Patients failing at least one
      chemotherapy regimen were eligible. Design provided PF-03446962 10 mg/Kg
      intravenously fortnightly until disease progression (PD) or unacceptable
      toxicity. Two-month progression-free survival (PFS) was the primary endpoint. The
      trial was registered with ClinicalTrials.gov, number NCT01620970. Fourteen
      patients were enrolled from October 2012 to July 2013. Median age was 64 years
      (interquartile range [IQR]: 58.2-69.5), 9 patients had a Bellmunt score of 1-2,
      median number of prior drugs was 3. One stable disease and 13 PD were recorded
      and the study met the futility stopping rule of interim analysis. Median PFS was
      1.8 months (95 %CI, 1.4-2.0). After a median follow up of 7.4 months (IQR 4.5
      10.9), 8 patients are alive. Median overall survival (OS) was 8 months (95 %CI,
      2.9-not estimable). Most common toxicities were thrombocytopenia (G1-2 in 5
      cases, persistent G3 in one, with 3 dose delays and 1 dose interruption), fatigue
      and abdominal pain (G1-2 in 4 cases each). Impairment of quality of life (ESAS
      score) was observed as well as an increase from baseline to +2 month median
      levels of vascular endothelial growth factor (VEGF) and interleukin-8. PF
      03446962 had no activity as single drug in refractory UC and we do not recommend
      further investigation outside of the combination with agents targeting the VEGF
      receptor axis.

PMID- 24566708
TI  - Donor-derived CD4(+)/CCR7(+) T-cell partial selective depletion does not alter
      acquired anti-infective immunity.
AB  - In previous studies, we observed that a high proportion of donor-derived CD4(+) T
      cells expressing the chemokine receptor 7 (CCR7) was a major determinant of acute
      GVHD, without interfering with the incidence of other post-transplant outcomes,
      especially relapse and nonrelapse mortality rates. Here, we investigated in vitro
      the impact of partially selective CD4(+)/CCR7(+) T lymphocytes on acquired anti
      infective immune response in 10 donors who underwent G-CSF-primed PBSC
      collection. Similar quantitative and functional proliferative reactions were
      observed in lymphocyte cultures in the presence of adenovirus and pp65 Ags with
      unmanipulated and partially depleted donor samples. No responses were observed in
      the presence of human T-cell lymphotropic virus type 1 used as a negative
      control. These results complete the proof of concept needed to build a clinical
      trial investigating partially selective CD4(+)/CCR7(+) T cell-depleted allo-SCT. 

PMID- 24566709
TI  - Impact of extracorporeal photopheresis on skin scores and quality of life in
      patients with steroid-refractory chronic GVHD.
AB  - There are few prospective studies evaluating the role of extracorporeal
      photopheresis (ECP) in chronic GVHD (cGVHD) and only occasional reports of the
      effect of ECP on patients' quality of life (QoL). We report a single-centre
      prospective study of patients undergoing fortnightly ECP for moderate or severe
      cGVHD. Response was assessed after 6 months of treatment using NIH scoring
      criteria and reduction in immunosuppression. QoL assessments were undertaken at
      baseline and at 6 months using the chronic GVHD symptom scale (cGVHD SS) and
      dermatology life quality index (DLQI). An intention-to-treat analysis showed that
      19/38 (50%) of patients had a complete or partial response. Twenty-seven out of
      38 patients completed 6 months of ECP treatment and 70% (19/27) had a complete or
      partial response. Eighty per cent of patients who completed 6 months of ECP
      treatment had a reduction in immunosuppression dose. A subset of patients
      completed QoL questionnaires. Seventeen out of 18 patients (94%) showed an
      improvement in scores. The mean cGVHD SS and mean DLQI score were both
      significantly lower after 6 months of ECP (22 compared with 36, P=0.012 and 3.4
      compared with 6.9, P=0.009, respectively). This study confirms that ECP can lead
      to objective clinical responses and, in addition, may lead to an improvement in
      QoL in cGVHD. 

PMID- 24566710
TI  - Risk factors for thrombotic microangiopathy in allogeneic hematopoietic stem cell
      recipients receiving GVHD prophylaxis with tacrolimus plus MTX or sirolimus.
AB  - Transplantation-associated thrombotic microangiopathy (TA-TMA) is a feared
      complication of allogeneic hematopoietic SCT (HSCT) owing to its high mortality
      rate. The use of calcineurin inhibitors or sirolimus (SIR) for GVHD prophylaxis
      has been suggested as a potential risk factor. However, the impact of tacrolimus
      (TAC) and SIR combinations on the increased risk of TA-TMA is currently not well
      defined. We retrospectively analyzed the incidence of TA-TMA in 102 allogeneic
      HSCT recipients who consecutively received TAC plus SIR (TAC/SIR) (n=68) or plus
      MTX (TAC/MTX)+/-ATG (n=34) for GVHD prophylaxis. No significant differences were
      observed in the incidence of TA-TMA between patients receiving TAC/SIR vs
      TAC/MTX+/-ATG (7.4% vs 8.8%, P=0.8). Only grade III-IV acute GVHD, previous HSCT
      and serum levels of TAC >25 ng/mL were associated with a greater risk of TA-TMA.
      Patients developing TA-TMA have significantly poorer survival (P<0.001); however,
      TA-TMA ceased to be an independent prognostic factor when it was included in a
      multivariate model. In conclusion, the combination of TAC/SIR does not appear to
      pose a higher risk of TA-TMA. By contrast, we identified three different risk
      groups for developing TA-TMA. 

PMID- 24566713
TI  - Infused neutrophil dose and haematopoietic recovery in patients undergoing
      autologous transplantation.

PMID- 24566711
TI  - Apoptotic signaling through Fas and TNF receptors ameliorates GVHD in mobilized
      peripheral blood grafts.
AB  - Mobilized peripheral blood (mPB) is a prevalent source of hematopoietic
      progenitors for transplantation; however, allogeneic and haploidentical
      transplants are often accompanied by severe GVHD. Following the observation that
      murine GVHD is ameliorated by pretransplant donor cell exposure to Fas-ligand
      (FasL) without host-specific sensitization, we assessed the susceptibility of mPB
      cells to spontaneous and receptor-induced apoptosis as a possible approach to
      GVHD prophylaxis. Short incubation for 4 h resulted in spontaneous apoptosis of
      50% of the T and B lymphocytes and 60% myeloid cells. Although expression of Fas
      and TNF-R1 was proportionate to fractional apoptosis, cell death was dominated by
      spontaneous apoptosis. Functional assays revealed that the death receptors
      modulated mPB graft composition as compared with incubation in medium, without
      detectable quantitative variations. Removal of dead cells increased the frequency
      of mPB myeloid progenitors (P<0.001 vs medium), and recipients of mPB exposed to
      death ligands displayed reduced GVHD (P<0.01 vs medium) and improved survival
      following lipopolysacharide stimulation. mPB grafts exposed to the apoptotic
      challenge retained SCID reconstituting potential and graft versus tumor activity.
      These data emphasize that short-term exposure of mPB grafts to an apoptotic
      challenge is effective in reduction of GVHD effector activity. 

PMID- 24566714
TI  - Carrier localization and electronic phase separation in a doped spin-orbit-driven
      Mott phase in Sr3(Ir(1-x)Ru(x))2O7.
AB  - Interest in many strongly spin-orbit-coupled 5d-transition metal oxide insulators
      stems from mapping their electronic structures to a J(eff)=1/2 Mott phase. One of
      the hopes is to establish their Mott parent states and explore these systems'
      potential of realizing novel electronic states upon carrier doping. However, once
      doped, little is understood regarding the role of their reduced Coulomb
      interaction U relative to their strongly correlated 3d-electron cousins. Here we
      show that, upon hole-doping a candidate J(eff)=1/2 Mott insulator, carriers
      remain localized within a nanoscale phase-separated ground state. A percolative
      metal-insulator transition occurs with interplay between localized and itinerant
      regions, stabilizing an antiferromagnetic metallic phase beyond the critical
      region. Our results demonstrate a surprising parallel between doped 5d- and 3d
      electron Mott systems and suggest either through the near-degeneracy of nearby
      electronic phases or direct carrier localization that U is essential to the
      carrier response of this doped spin-orbit Mott insulator.

PMID- 24566712
TI  - Haploidentical SCT: the mechanisms underlying the crossing of HLA barriers.
AB  - Research on the different mechanisms for crossing HLA barriers has progressed
      over the past 10 years. General outlines have come into view for a solution to
      this issue and are often presented as 'haploidentical SCT' immunology. In this
      review, we discuss several mechanisms that have recently been described in ex
      vivo and in vivo settings that can either avoid GVHD or promote hematopoietic
      reconstitution in haploidentical settings. The host and donor T-cell responses to
      allogeneic HLA molecules are a fundamental obstacle to the successful application
      of haploidentical transplantation, which results in unacceptably high incidences
      of GVHD and graft rejection. Thus, the T-cell response is a central factor in the
      establishment of a novel haploidentical transplant protocol with superior
      outcomes. 

PMID- 24566716
TI  - Fixing the mirrors: a feasibility study of the effects of dance movement therapy
      on young adults with autism spectrum disorder.
AB  - From the 1970s on, case studies reported the effectiveness of therapeutic
      mirroring in movement with children with autism spectrum disorder. In this
      feasibility study, we tested a dance movement therapy intervention based on
      mirroring in movement in a population of 31 young adults with autism spectrum
      disorder (mainly high-functioning and Asperger's syndrome) with the aim to
      increase body awareness, social skills, self-other distinction, empathy, and well
      being. We employed a manualized dance movement therapy intervention implemented
      in hourly sessions once a week for 7 weeks. The treatment group (n = 16) and the
      no-intervention control group (n = 15) were matched by sex, age, and symptom
      severity. Participants did not participate in any other therapies for the
      duration of the study. After the treatment, participants in the intervention
      group reported improved well-being, improved body awareness, improved self-other
      distinction, and increased social skills. The dance movement therapy-based
      mirroring approach seemed to address more primary developmental aspects of autism
      than the presently prevailing theory-of-mind approach. Results suggest that dance
      movement therapy can be an effective and feasible therapy approach for autism
      spectrum disorder, while future randomized control trials with bigger samples are
      needed. 

PMID- 24566717
TI  - The influence of maternal language responsiveness on the expressive speech
      production of children with autism spectrum disorders: a microanalysis of mother
      child play interactions.
AB  - Adult responsiveness is related to language development both in young typically
      developing children and in children with autism spectrum disorders, such that
      parents who use more responsive language with their children have children who
      develop better language skills over time. This study used a micro-analytic
      technique to examine how two facets of maternal utterances, relationship to child
      focus of attention and degree of demandingness, influenced the immediate use of
      appropriate expressive language of preschool-aged children with autism spectrum
      disorders (n = 28) and toddlers with typical development (n = 16) within a
      naturalistic mother-child play session. Mothers' use of follow-in demanding
      language was most likely to elicit appropriate expressive speech in both children
      with autism spectrum disorders and children with typical development. For
      children with autism spectrum disorders, but not children with typical
      development, mothers' use of orienting cues conferred an additional benefit for
      expressive speech production. These findings are consistent with the naturalistic
      behavioral intervention philosophy and suggest that following a child's lead
      while prompting for language is likely to elicit speech production in children
      with autism spectrum disorders and children with typical development.
      Furthermore, using orienting cues may help children with autism spectrum
      disorders to verbally respond. 

PMID- 24566718
TI  - Building and optimizing a virus-specific T cell receptor library for targeted
      immunotherapy in viral infections.
AB  - Restoration of antigen-specific T cell immunity has the potential to clear
      persistent viral infection. T cell receptor (TCR) gene therapy can reconstitute
      CD8 T cell immunity in chronic patients. We cloned 10 virus-specific TCRs
      targeting 5 different viruses, causing chronic and acute infection. All 10 TCR
      genetic constructs were optimized for expression using a P2A sequence, codon
      optimization and the addition of a non-native disulfide bond. However, maximum
      TCR expression was only achieved after establishing the optimal orientation of
      the alpha and beta chains in the expression cassette; 9/10 TCRs favored the beta
      P2A-alpha orientation over alpha-P2A-beta. Optimal TCR expression was associated
      with a significant increase in the frequency of IFN-gamma+ T cells. In addition,
      activating cells for transduction in the presence of Toll-like receptor ligands
      further enhanced IFN-gamma production. Thus, we have built a virus-specific TCR
      library that has potential for therapeutic intervention in chronic viral
      infection or virus-related cancers. 

PMID- 24566719
TI  - Dose error from deviation of dwell time and source position for high dose-rate
      192Ir in remote afterloading system.
AB  - The influence of deviations in dwell times and source positions for (192)Ir HDR
      RALS was investigated. The potential dose errors for various kinds of
      brachytherapy procedures were evaluated. The deviations of dwell time DeltaT of a
      (192)Ir HDR source for the various dwell times were measured with a well-type
      ionization chamber. The deviations of source position DeltaP were measured with
      two methods. One is to measure actual source position using a check ruler device.
      The other is to analyze peak distances from radiographic film irradiated with 20
      mm gap between the dwell positions. The composite dose errors were calculated
      using Gaussian distribution with DeltaT and DeltaP as 1sigma of the measurements.
      Dose errors depend on dwell time and distance from the point of interest to the
      dwell position. To evaluate the dose error in clinical practice, dwell times and
      point of interest distances were obtained from actual treatment plans involving
      cylinder, tandem-ovoid, tandem-ovoid with interstitial needles, multiple
      interstitial needles, and surface-mold applicators. The DeltaT and DeltaP were 32
      ms (maximum for various dwell times) and 0.12 mm (ruler), 0.11 mm (radiographic
      film). The multiple interstitial needles represent the highest dose error of 2%,
      while the others represent less than approximately 1%. Potential dose error due
      to dwell time and source position deviation can depend on kinds of brachytherapy
      techniques. In all cases, the multiple interstitial needles is most susceptible.

PMID- 24566720
TI  - Long-term pathological and immunohistochemical features in the liver after
      intraoperative whole-liver irradiation in rats.
AB  - Radiation therapy (RT) has become particularly important recently for treatment
      of liver tumors, but there are few experimental investigations pertaining to
      radiation-induced liver injuries over long-term follow-up periods. Thus, the
      present study examined pathological liver features over a 10-month period using
      an intraoperative whole-liver irradiation model. Liver function tests were
      performed in blood samples, whereas cell death, cell proliferation, and fibrotic
      changes were evaluated pathologically in liver tissues, which were collected from
      irradiated rats 24 h, 1, 2, 4 and 40 weeks following administration of single
      irradiation doses of 0 (control), 15 or 30 Gy. The impaired liver function,
      increased hepatocyte number, and decreased apoptotic cell proportion observed in
      the 15 Gy group, but not the 30 Gy group, returned to control group levels after
      40 weeks; however, the Ki-67 indexes in the 15 Gy group were still higher than
      those in the control group after 40 weeks. Azan staining showed a fibrotic
      pattern in the irradiated liver in the 30 Gy group only, but the expression
      levels of alpha smooth muscle actin (alpha-SMA) and transforming growth factor
      beta 1 (TGF-beta1) in both the 15 and 30 Gy groups were significantly higher than
      those in the control group (P < 0.05). There were differences in the pathological
      features of the irradiated livers between the 15 Gy and 30 Gy groups, but TGF
      beta1 and alpha-SMA expression patterns supported the gradual progression of
      radiation-induced liver fibrosis in both groups. These findings will be useful in
      the future development of protective drugs for radiation-induced liver injury.

PMID- 24566721
TI  - Dose-volume histogram parameters of high-dose-rate brachytherapy for Stage I-II
      cervical cancer (<=4cm) arising from a small-sized uterus treated with a point A
      dose-reduced plan.
AB  - We investigated the rectal dose-sparing effect and tumor control of a point A
      dose-reduced plan in patients with Stage I-II cervical cancer (<=4 cm) arising
      from a small-sized uterus. Between October 2008 and August 2011, 19 patients with
      Stage I-II cervical cancer (<=4 cm) were treated with external beam radiotherapy
      (EBRT) for the pelvis and CT-guided brachytherapy. Seven patients were treated
      with brachytherapy with standard loading of source-dwell positions and a fraction
      dose of 6 Gy at point A (conventional brachy-plan). The other 12 patients with a
      small uterus close to the rectum or small intestine were treated with
      brachytherapy with a point A dose-reduction to match D2cc of the rectum and <6 Gy
      as the dose constraint ('point A dose-reduced plan') instead of the 6-Gy plan at
      point A ('tentative 6-Gy plan'). The total doses from EBRT and brachytherapy were
      added up and normalized to a biological equivalent dose of 2 Gy per fraction
      (EQD2). The median doses to the high-risk clinical target volume (HR-CTV) D90 in
      the conventional brachy-plan, tentative 6-Gy plan and point A dose-reduced plan
      were 62 GyEQD2, 80 GyEQD2 and 64 GyEQD2, respectively. The median doses of rectal
      D2cc in the corresponding three plans were 42 GyEQD2, 62 GyEQD2 and 51 GyEQD2,
      respectively. With a median follow-up period of 35 months, three patients
      developed Grade-1 late rectal complications and no patients developed local
      recurrence. Our preliminary results suggested that CT-guided brachytherapy using
      an individualized point A dose-reduced plan might be useful for reducing late
      rectal complications while maintaining primary tumor control.

PMID- 24566723
TI  - Gender identity shows a high correlation with Prader score in patients with
      disorders of sex development (DSD) presenting in mid childhood.
AB  - OBJECTIVE: In developing countries like Bangladesh, delayed presentation for
      disorders of sex development (DSD) is common, and provides some special problems
      for management. There remains significant controversy about appropriate sex
      assignment in this group. We aimed, therefore, to assess gender identity (GI) in
      50 consecutive patients with DSD presenting to a referral centre in Chittagong,
      Bangladesh, and correlate it with Prader score, to see if the latter could be
      used to predict GI. METHODS: A cross-sectional, case-control study of 50
      consecutive children with DSD and 50 children with vascular anomalies was
      conducted in the Pediatric Surgical Clinic, Chittagong Medical College and
      Hospital. After informed consent, patients and controls provided oral answers to
      a GI questionnaire and had a detailed history and physical examination. Sex-typed
      activities were assessed by observations of a structured toy play and the child's
      selection of a toy to keep. Both patients and parents then completed the Child
      Game Participation Questionnaire. RESULTS: There were no differences in age (2-16
      years, mean 8.74) between controls and DSD patients (11 46, XX DSD, 32 46, XY
      DSD, 4 MGD, 3 ovo-testicular DSD). Fifteen of the DSD patients (30 %) came from
      consanguineous marriages and only 2 of the control patients had consanguinity of
      their parents. For the 13-question GI interview, there was no overall difference
      between DSD cases and controls. For the 46, XX DSD subgroup, there was a
      significantly higher score (11.1 +/- 7.1) compared with control girls (4.5 +/-
      4.7) (p < 0.05), while for DSD and control boys, there was a positive correlation
      with age and GI (p < 0.01). Prader score correlated with GI score in both control
      (r = 0.91) and DSD patients (r = 0.75) (p < 0.01), DSD girls played significantly
      less with girls' toys than controls (p < 0.01), but there was no differences for
      the boys. Composite scores on GI and gender-related behaviour correlated with
      Prader score for DSD patients (r = 0.61) (p < 0.01). CONCLUSION: This study
      supports the view that GI and gender-role behaviour should be assessed routinely
      in DSD patients presenting after the neonatal period, so that sex assignment is
      in accordance with behaviour. Prader scores showed a good correlation with GI and
      gender role behaviour.

PMID- 24566722
TI  - Asynchronous activation of calcium and potassium currents by isoproterenol in
      canine ventricular myocytes.
AB  - Adrenergic activation of L-type Ca(2+) and various K(+) currents is a crucial
      mechanism of cardiac adaptation; however, it may carry a substantial
      proarrhythmic risk as well. The aim of the present work was to study the timing
      of activation of Ca(2+) and K(+) currents in isolated canine ventricular cells in
      response to exposure to isoproterenol (ISO). Whole cell configuration of the
      patch-clamp technique in either conventional voltage clamp or action potential
      voltage clamp modes were used to monitor I(Ca), I(Ks), and I(Kr), while action
      potentials were recorded using sharp microelectrodes. ISO (10 nM) elevated the
      plateau potential and shortened action potential duration (APD) in subepicardial
      and mid-myocardial cells, which effects were associated with multifold
      enhancement of I(Ca) and I(Ks) and moderate stimulation of I(Kr). The ISO-induced
      plateau shift and I(Ca) increase developed faster than the shortening of APD and
      stimulation of I(Ks) and I(Kr). Blockade of beta1-adrenoceptors (using 300 nM CGP
      20712A) converted the ISO-induced shortening of APD to lengthening, decreased its
      latency, and reduced the plateau shift. In contrast, blockade of beta2
      adrenoceptors (by 50 nM ICI 118,551) augmented the APD-shortening effect and
      increased the latency of plateau shift without altering its magnitude. All
      effects of ISO were prevented by simultaneous blockade of both receptor types.
      Inhibition of phosphodiesterases decreased the differences observed in the turn
      on of the ISO-induced plateau shift and APD shortening. ISO-induced activation of
      I(Ca) is turned on faster than the stimulation of I(Ks) and I(Kr) in canine
      ventricular cells due to the involvement of different adrenergic pathways and
      compartmentalization.

PMID- 24566724
TI  - Is there a need for bacterial endocarditis prophylaxis in patients undergoing
      urological procedures?
AB  - Heart valve repair or replacement is a serious problem.The focused update on
      infective endocarditis of American College of Cardiology/American Heart
      Association 2008 (ACC/AHA guidelines) and Guidelines on the prevention,
      diagnosis, and treatment of infective endocarditis (new version 2009) of the
      European Society of Cardiology (ESC guidelines) describe prophylaxis against
      infective endocarditis as not recommended for urinary tract procedures in the
      absence of active infection. A statistical association has been recently shown
      between urological procedures and the development of infective endocarditis. New
      evidences concerning infective endocarditis due to Actinobaculum schaalii,
      Neisseria gonorrhoeae, Streptococcus agalactiae, Enterococcus faecalis,
      Pseudomonas aeruginosa, Aerococci and Staphylococcus aureus, and new findings
      indicate there is a need for bacterial endocarditis prophylaxis in patients
      undergoing urological procedures especially in elderly patients and in cancer and
      immunocompromised patients, to avoid serious consequences. 

PMID- 24566725
TI  - Is there a need for bacterial endocarditis prophylaxis in patients undergoing
      gastrointestinal endoscopy?
AB  - Heart valve repair or replacement is a serious problem. Patients can benefit from
      an open dialogue between both cardiologists and gastroenterologists for the
      optimal effective patients care. The focused update on infective endocarditis of
      the American College of Cardiology/American Heart Association 2008 (ACC/AHA
      guidelines) and guidelines on the prevention, diagnosis, and treatment of
      infective endocarditis (new version 2009) of the European Society of Cardiology
      (ESC guidelines) describe prophylaxis against infective endocarditis (IE) as not
      recommended for gastroscopy and colonoscopy in the absence of active infection
      but increasing evidence suggests that the role of IE antibiotic prophylaxis
      remains a dark side of the cardio-oncology prevention. New evidences concerning
      infective endocarditis due to Streptococcus bovis, Streptococcus agalactiae,
      Enterococcus faecalis, Enterococcus faecium, Enterococcus durans, and new
      findings indicate that there is a need for bacterial endocarditis prophylaxis in
      patients undergoing gastrointestinal endoscopy especially in elderly patients and
      in cancer and immunocompromised patients, to avoid serious consequences. 

PMID- 24566726
TI  - Expression of beta-amyloid precursor protein in refractory epilepsy.
AB  - beta-amyloid precursor protein (beta-APP), also known as Abeta peptide, has a key
      role in the pathogenesis of Alzheimer's disease, and is also likely to be
      involved in the development of refractory epilepsy. The mechanism behind the
      association between beta-APP and refractory epilepsy remains to be elucidated.
      The aim of the present study was to examine the levels of APP mRNA and beta-APP
      protein in patients with refractory epilepsy. Tissue samples were obtained from
      patients with chronic pharmacoresistant epilepsy who underwent surgery. Levels of
      APP mRNA and beta-APP protein in epileptic temporal lobe and hippocampal tissue
      were assessed using quantitative polymerase chain reaction, immunohistochemistry
      and immunofluorescence. The expression levels of protein significantly increased
      in the temporal cortex and the hippocampus of the patients with epilepsy. beta
      APP may thus contribute to the pathogenesis of refractory epilepsy.

PMID- 24566727
TI  - Time from cardiac catheterization to cardiac surgery: a risk factor for acute
      kidney injury?.
AB  - OBJECTIVES: Acute kidney injury can occur after cardiac catheterization and
      cardiac surgery. The negative effects of the contrast media and cardiopulmonary
      bypass on renal function may be additive when performed in close succession. The
      results in the literature are, however, conflicting. METHODS: Preoperative,
      operative, perioperative and postoperative variables of 573 consecutive adult
      patients who underwent cardiac surgery on cardiopulmonary bypass were collected
      prospectively. Acute kidney injury (AKI) was defined according to the Acute
      Kidney Injury Network criteria based on changes in serum creatinine level within
      48 h of surgery. RESULTS: Acute kidney injury was detected in 233 patients (41%).
      In a multivariate analysis, older age (P = 0.01), longer cardiopulmonary bypass
      time (P = 0.003), lower preoperative haematocrit level (P = 0.02) and higher body
      mass index (P = 0.001) were found to be independently associated with development
      of acute kidney injury. Analysis of the time from cardiac catheterization to
      surgery by logistic regression modelling did not show any significant change in
      the risk of acute kidney injury. Risk related to time from catheterization to
      surgery was not increased even in the patients with elevated preprocedural
      creatinine levels (>106 MUmol l(-1); P = 0.23), left ventricular dysfunction
      (ejection fraction <40%; P = 0.19) and older age (>=70 years; P = 0.86).
      CONCLUSIONS: The time from cardiac catheterization to cardiac surgery is not a
      risk factor for the development of postoperative acute kidney injury even in
      patients with other risk factors. Surgical intervention should not be delayed in
      emergency or urgent cases. The optimization of renal function seems to be the
      correct strategy in clinically stable patients with risk factors for acute kidney
      injury.

PMID- 24566729
TI  - Organ damage and hepatic lipid accumulation in carp (Cyprinus carpio L.) after
      feed-borne exposure to the mycotoxin, deoxynivalenol (DON).
AB  - Deoxynivalenol (DON) frequently contaminates animal feed, including fish feed
      used in aquaculture. This study intends to further investigate the effects of DON
      on carp (Cyprinus carpio L.) at concentrations representative for commercial fish
      feeds. Experimental feeding with 352, 619 or 953 MUg DON kg(-1) feed resulted in
      unaltered growth performance of fish during six weeks of experimentation, but
      increased lipid peroxidation was observed in liver, head kidney and spleen after
      feeding of fish with the highest DON concentration. These effects of DON were
      mostly reversible by two weeks of feeding the uncontaminated control diet.
      Histopathological scoring revealed increased liver damage in DON-treated fish,
      which persisted even after the recovery phase. At the highest DON concentration,
      significantly more fat, and consequently, increased energy content, was found in
      whole fish body homogenates. This suggests that DON affects nutrient metabolism
      in carp. Changes of lactate dehydrogenase (LDH) activity in kidneys and muscle
      and high lactate levels in serum indicate an effect of DON on anaerobic
      metabolism. Serum albumin was reduced by feeding the medium and a high dosage of
      DON, probably due to the ribotoxic action of DON. Thus, the present study
      provides evidence of the effects of DON on liver function and metabolism.

PMID- 24566730
TI  - Identification of suitable qPCR reference genes in leaves of Brassica oleracea
      under abiotic stresses.
AB  - Real-time quantitative PCR is nowadays a standard method to study gene expression
      variations in various samples and experimental conditions. However, to interpret
      results accurately, data normalization with appropriate reference genes appears
      to be crucial. The present study describes the identification and the validation
      of suitable reference genes in Brassica oleracea leaves. Expression stability of
      eight candidates was tested following drought and cold abiotic stresses by using
      three different softwares (BestKeeper, NormFinder and geNorm). Four genes
      (BolC.TUB6, BolC.SAND1, BolC.UBQ2 and BolC.TBP1) emerged as the most stable
      across the tested conditions. Further gene expression analysis of a drought- and
      a cold-responsive gene (BolC.DREB2A and BolC.ELIP, respectively), confirmed the
      stability and the reliability of the identified reference genes when used for
      normalization in the leaves of B. oleracea. These four genes were finally tested
      upon a benzene exposure and all appeared to be useful reference genes along this
      toxicological condition. These results provide a good starting point for future
      studies involving gene expression measurement on leaves of B. oleracea exposed to
      environmental modifications. 

PMID- 24566732
TI  - Extensive cerebral microhemorrhages caused by acute disseminated intravascular
      coagulation secondary to sepsis.

PMID- 24566731
TI  - Risk of atrial fibrillation, stroke, and death after radiofrequency catheter
      ablation of typical atrial flutter.
AB  - OBJECTIVE: The purpose of this study was to assess the incidence, predictors, and
      prognostic clinical impact of atrial fibrillation (AF) over time after
      cavotricuspid isthmus (CTI) ablation of typical atrial flutter (AFL). METHODS:
      This was a follow-up observational study using 408 patients who underwent CTI AFL
      ablation between 1998 and 2010. The relationships between the different
      predictors and the outcomes (AF, stroke, and death) were modeled by means of
      multistate Cox model analyses. RESULTS: The incident rate of AF per 100 person
      years during follow-up was 10.2 (95 % CI 8.7-11.8). Prior AF and chronic
      obstructive pulmonary disease (COPD) were the only independent variables to
      predict AF occurrence in the population. Their hazard ratios (HRs) were 2.55 (95
      % CI 1.84-3.52) and 1.56 (95 % CI 1.08-2.27), respectively. Patients who
      transitioned to AF had an increased risk of death by an HR of 2.82 (95 % CI 1.88
      4.70) and an increased risk of stroke by an HR of 2.93 (95 % CI 1.12-8.90). Age,
      COPD, and heart failure (HF) were predictive factors of death by HRs of 1.05 (95
      % CI 1.00-1.08), 2.85 (95 % CI 1.39-5.83), and 2.72 (95 % CI 1.15-6.40),
      respectively. Age, smoking, COPD, and HF were predictive factors of death in the
      group of patients with AF during follow-up. HRs were 1.07 (95 % CI 1.02-1.12),
      2.55 (95 % CI 1.55-4.21), 7.60 (95 % CI 3.01-19.16), and 3.07 (95 % CI 1.18
      7.95), respectively. CONCLUSIONS: The transition to AF after CTI AFL ablation was
      high during a long-term follow-up period and maintained over time. Prior AF and
      COPD were the primary predictors of transition to AF after CTI AFL ablation.
      Patients who transitioned to AF had an increased risk of stroke and a more than
      twofold mortality rate. These clinical implications make it necessary to
      investigate AF after CTI ablation.

PMID- 24566728
TI  - Tetrodotoxin: chemistry, toxicity, source, distribution and detection.
AB  - Tetrodotoxin (TTX) is a naturally occurring toxin that has been responsible for
      human intoxications and fatalities. Its usual route of toxicity is via the
      ingestion of contaminated puffer fish which are a culinary delicacy, especially
      in Japan. TTX was believed to be confined to regions of South East Asia, but
      recent studies have demonstrated that the toxin has spread to regions in the
      Pacific and the Mediterranean. There is no known antidote to TTX which is a
      powerful sodium channel inhibitor. This review aims to collect pertinent
      information available to date on TTX and its analogues with a special emphasis on
      the structure, aetiology, distribution, effects and the analytical methods
      employed for its detection. 

PMID- 24566733
TI  - Aspirin decreases systemic exposure to clopidogrel through modulation of P
      glycoprotein but does not alter its antithrombotic activity.
AB  - Decreased oral clopidogrel absorption caused by induction of intestinal
      permeability glycoprotein (P-gp) expression after aspirin administration was
      observed in rats. This study evaluated the effect of aspirin coadministration on
      the pharmacokinetics/pharmacodynamics of clopidogrel in humans. A single 75-mg
      dose of clopidogrel was orally administered before and after 2 and 4 weeks of
      once-daily 100-mg aspirin administration in 18 healthy volunteers who were
      recruited based on CYP2C19 and PON1 genotypes. Plasma concentrations of
      clopidogrel and its active metabolite, H4, and relative platelet inhibition (RPI)
      were determined. The P-gp microRNA miR-27a increased by up to 7.67-fold (P =
      0.004) and the clopidogrel area under the concentration-time curve (AUC)
      decreased by 14% (P > 0.05), but the AUC of H4 remained unchanged and RPI
      increased by up to 15% (P = 0.002) after aspirin administration. These findings
      indicate low-dose aspirin coadministration may decrease clopidogrel
      bioavailability but does not decrease its efficacy. 

PMID- 24566734
TI  - Association analysis of genetic polymorphisms in genes related to sunitinib
      pharmacokinetics, specifically clearance of sunitinib and SU12662.
AB  - Interpatient variability in the pharmacokinetics (PK) of sunitinib is high.
      Single nucleotide polymorphisms (SNPs) in PK candidate genes have been associated
      with the efficacy and toxicity of sunitinib, but whether these SNPs truly affect
      the PK of sunitinib remains to be elucidated. This multicenter study involving
      114 patients investigated whether these SNPs and haplotypes in genes encoding
      metabolizing enzymes or efflux transporters are associated with the clearance of
      sunitinib and its active metabolite SU12662. SNPs were tested as covariates in a
      population PK model. From univariate analysis, we found that the SNPs in CYP3A4,
      CYP3A5, and ABCB1 were associated with the clearance of both sunitinib and
      SU12662. In multivariate analysis, CYP3A4*22 was found to be eliminated last with
      an effect size of -22.5% on clearance. Observed effect sizes are below the
      interindividual variability in clearance and are therefore too limited to
      directly guide individual dosing of sunitinib. 

PMID- 24566735
TI  - Magnetic nanosensors optimized for rapid and reversible self-assembly.
AB  - Magnetic nanoparticle-based sensors for MRI have been accelerated to a timescale
      of seconds using densely-functionalized particles of small size. Parameters that
      increase response rates also result in large nuclear magnetic relaxation rate and
      light scattering changes, allowing signals to be detected almost immediately
      after changes in calcium concentration. 

PMID- 24566737
TI  - Microstructural percolation assisted breakthrough of trade-off between strength
      and ductility in CuZr-based metallic glass composites.
AB  - As two important mechanical properties, strength and ductility generally tend to
      be muturally exclusive in conventional engineering materials. The breakthrough of
      such a trade-off has been potentiated by the recently developed CuZr-based bulk
      metallic glass (BMG) composites ductilized by a shape memory CuZr(B2) phase. Here
      the microstructural dependences of tensile properties for the CuZr-based BMG
      composites were elucidated qualitatively and modeled quantitatively, and the
      underlying mechanisms were unraveled. Through the microstructural percolation
      induced by matching the length scales of particle size and interparticle spacing,
      a notable breakthrough was achieved in the composites that the general conflicts
      between strength and ductility can be defeated. This study is expected to greatly
      aid in the microstructural design and tailoring for improved properties of BMG
      composites. It also has implications for the development of strong and ductile
      materials in the future. 

PMID- 24566739
TI  - Speed and accuracy of a point of care web-based knowledge resource for
      clinicians: a controlled crossover trial.
AB  - BACKGROUND: Effective knowledge translation at the point of care requires that
      clinicians quickly find correct answers to clinical questions, and that they have
      appropriate confidence in their answers. Web-based knowledge resources can
      facilitate this process. OBJECTIVE: The objective of our study was to evaluate a
      novel Web-based knowledge resource in comparison with other available Web-based
      resources, using outcomes of accuracy, time, and confidence. METHODS: We
      conducted a controlled, crossover trial involving 59 practicing clinicians. Each
      participant answered questions related to two clinical scenarios. For one
      scenario, participants used a locally developed Web-based resource, and for the
      second scenario, they used other self-selected Web-based resources. The local
      knowledge resource ("AskMayoExpert") was designed to provide very concise
      evidence-based answers to commonly asked clinical questions. Outcomes included
      time to a correct response with at least 80% confidence (primary outcome),
      accuracy, time, and confidence. RESULTS: Answers were more often accurate when
      using the local resource than when using other Web-based resources, with odds
      ratio 6.2 (95% CI 2.6-14.5; P<.001) when averaged across scenarios. Time to find
      an answer was faster, and confidence in that answer was consistently higher, for
      the local resource (P<.001). Overconfidence was also less frequent with the local
      resource. In a time-to-event analysis, the chance of responding correctly with at
      least 80% confidence was 2.5 times greater when using the local resource than
      with other resources (95% CI 1.6-3.8; P<.001). CONCLUSIONS: Clinicians using a
      Web-based knowledge resource designed to provide quick, concise answers at the
      point of care found answers with greater accuracy and confidence than when using
      other self-selected Web-based resources. Further study to improve the design and
      implementation of knowledge resources may improve point of care learning.

PMID- 24566736
TI  - Practical guidelines for therapeutic drug monitoring of anticancer tyrosine
      kinase inhibitors: focus on the pharmacokinetic targets.
AB  - There is accumulating evidence for potential benefits of therapeutic drug
      monitoring (TDM) in the treatment of cancer with tyrosine kinase inhibitors
      (TKIs). Relationships between exposure and response (efficacy/toxicity) have been
      established for several TKIs. For example, the pharmacokinetic targets for
      efficacy of imatinib, sunitinib and pazopanib have been defined as trough plasma
      concentrations (Ctrough) of >1,000, >50 and >20,000 ng/mL for selected
      indications, respectively. Dose adjustment based on pharmacokinetic targets could
      therefore increase response rates and duration. Furthermore, with appropriate
      target concentrations defined, excessive side effects in patients using the
      current fixed dosing strategy may be prevented. This review provides a practical
      guideline for TDM for the currently approved TKIs at 28 February 2013. The focus
      of this article is on the elaboration of exposure and response relationships of
      TKIs with proposed pharmacokinetic targets, mainly Ctrough, and further on the
      interpretation of the pharmacokinetic targets with recommendations for dose
      titrations.

PMID- 24566740
TI  - The use of ancillary techniques to aid colonoscope insertion.
AB  - BACKGROUND: There is more to a high-quality colonoscopy than reaching the cecum
      or finding adenomas. Gentle insertion involves ancillary techniques, some of
      which are impossible in patients receiving deep sedation. The aim of this study
      was to assess the importance of ancillary techniques in achieving a comfortable,
      complete colonoscopy. METHODS: This was a prospective study of 500 consecutive
      outpatient colonoscopies performed by a single endoscopist. During the procedure,
      note was taken of various ancillary techniques used to facilitate insertion:
      turning the patient, patient holding their breath, abdominal pressure. The
      success of these techniques in helping scope advancement was also noted. After
      the procedure the patient was asked to rate the severity of their pain and their
      degree of satisfaction with the examination. RESULTS: A total of 238 women and
      262 men participated in the study, and colonoscopy was complete in 96.2 and
      98.5%, respectively. Overall, 97% of patients received versed alone (average dose
      2 mg), and 3% received a narcotic (average dose 46 U). Average pain score was 3.9
      on a scale of 1 (least pain) to 10 (worst pain), and average satisfaction with
      the procedure as a whole was 9.5 on a similar scale. Ancillary techniques of
      holding breath, directed abdominal pressure, and turning to the left, right, and
      prone were used in 46, 56, 17, 23, and 4% of examinations, respectively. Each
      technique was effective in helping insertion in over 70% of cases. Turning the
      patient was also used to clear stool, open the colon, or facilitate polypectomy
      in another 33 cases. Multiple techniques were used in 49% of patients.
      CONCLUSION: The use of ancillary techniques to facilitate colonoscope insertion
      helps avoid the expense and potential side effects of deep sedation.

PMID- 24566741
TI  - A safe method of vaginal longitudinal morcellation of bulky uterus with
      endometrial cancer in a bag at laparoscopy.
AB  - BACKGROUND: Total laparoscopic hysterectomy (TLH) is becoming an increasingly
      popular treatment in endometrial cancer. Intra-abdominal or vaginal uterus
      morcellation are well described and routinely practiced techniques in removing a
      benign bulky uterus but contraindicated in endometrial cancer. In malignancy, the
      uterus needs to be removed intact to avoid intraperitoneal spillage of the
      endometrial cancer cells, and a uterine size of 12 gestational weeks (g.w.) or
      larger has been considered a contraindication for the laparoscopic approach. The
      aim of our study was to evaluate the feasibility and safety of a sealed vaginal
      morcellation technique in a bag for endometrial cancer laparoscopic treatment.
      METHODS: We prospectively scheduled 12 patients affected by endometrial cancer
      with uterus bigger than 12 g.w. for endometrial cancer laparoscopic treatment.
      After performing TLH, a sterile plastic wrapping bag was inserted by a 12 mm
      camera port by rolling it onto the blunt probe. The uterus was covered from the
      fundus to the cervix, placing the free edges of the bag down into the manipulator
      cup with two blunt graspers. The specimen completely covered by the bag was then
      pushed down under direct laparoscopic vision through colpotomy and pulled out
      from the vagina. The uterus was morcellated by the vaginal route. RESULTS: All
      patients underwent laparoscopic treatment with vaginal uterine morcellation. The
      mean uterus weight was 290.8 +/- 79.7 g with a mean morcellation operative time
      of 12.1 min. All vaginal morcellations were completed successfully. All patients
      were without evidence of local or distant recurrence at the median follow-up time
      of 18 months. CONCLUSIONS: This technique allows the surgeon to morcellate a
      bulky uterus in cases of endometrial cancer and reduces the chance of neoplastic
      cell spillage during debulking at TLH. Vaginal morcellation following oncologic
      rules permits a rapid uterine extraction and may avoid a number of unnecessary
      laparotomies.

PMID- 24566742
TI  - A novel endoscopic fluorescent clip visible with near-infrared imaging during
      laparoscopic surgery in a porcine model.
AB  - BACKGROUND: In gastrointestinal cancer surgery, particularly in early cancer,
      accurate tumor localization is important in order to determine the extent of
      resection. In laparoscopic surgery, because of the inability to palpate the
      lesion, the most prevalent method of localization is endoscopic tattooing.
      However, complicated maneuvering makes it difficult to control local dye
      spreading and dye leakage into the intraperitoneal cavity. A simpler, safe method
      is needed. In this study, we developed a novel method for applying fluorescence
      coated endoscopic clips to visualize locations inside the colon during
      laparoscopic surgery. We tested the procedure in an in vivo porcine model and
      with ex vivo human colon tissues. METHODS: Bovine serum albumin was conjugated to
      indocyanine green or the succinimidyl ester CFTM 790 to form a pasty mixture,
      which was used to coat the front ends of endoscopic clips. The fluorescence
      coated clips were endoscopically placed on the mucosal surface of a porcine
      colon. Using an Olympus near-infrared laparoscopy system, we attempted to
      identify the fluorescent clips from the outer, serosal side of the porcine colon
      during laparoscopic surgery in vivo. The clips were also evaluated using ex vivo
      human colon tissues. RESULTS: After placing two clips on the inner, mucosal
      surface of the porcine colon, we used near-infrared laparoscopy to view them from
      the outer, serosal surface of the colon in real time during in vivo laparoscopic
      surgery. We also identified the fluorescence-coated clips through human colon
      tissues in an ex vivo study. CONCLUSIONS: We developed a novel, fluorescence
      coated clip that can be placed endoscopically for rapid, exact localization of
      colonic lesions. The clips were successfully visualized with near-infrared
      fluorescence imaging during laparoscopic surgery in an in vivo porcine model and
      in ex vivo human colon tissues.

PMID- 24566743
TI  - Roux-En-Y Fistulo-Jejunostomy as a salvage procedure in patients with post-sleeve
      gastrectomy fistula.
AB  - BACKGROUND: Sleeve gastrectomy (SG) is currently the most common bariatric
      procedure in France. It achieves both adequate excess weight loss and significant
      reduction of comorbidities. However, leak is still the most common complication
      after SG. Nevertheless, its risk of occurrence is <3% in specialized centers. Its
      management is difficult, long, and challenging. Although the procedure is
      commonly endoscopic and nonoperative, the management of post-SG fistulas could
      sometimes be surgical, including peritoneal lavage, abscess drainage, disrupted
      staple line suturing, resleeve, gastric bypass, or total gastrectomy. Roux-en-Y
      fistulojejunostomy (RYFJ) has been described as a salvage option. In this study,
      we report the early results of RYFJ for post-SG fistula, emphasizing indications,
      operative technique, and short-term outcome. METHODS: Between January 2007 and
      December 2012, we treated 62 patients with post-SG fistula. Before surgery, intra
      abdominal or thoracic abscesses or collections were either excluded or treated by
      computed tomographic scan-guided drainage or even surgery. Endoscopic stenting
      was then attempted. After optimization of the nutritional status in case of
      failure of endoscopic measures, some of the patients underwent RYFJ. RESULTS:
      Between January 2007 and December 2012, a total of 21 patients (16 women and 5
      men) had RYFJ for post-SG fistula. Mean age was 47 years (range, 22-59 years).
      Procedures were performed laparoscopically in all but 3 cases. The rate of
      secondary conversion to laparotomy was 11.1%. The was no mortality. The
      postoperative morbidity rate was less than 5%. The rate of fistula control was
      eventually 100%. CONCLUSIONS: RYFJ is a safe and feasible salvage procedure for
      the treatment of patients with post-SG fistula. Longer outcome analysis is,
      however, needed especially regarding the physiological and metabolic behavior of
      the procedure.

PMID- 24566744
TI  - Near-infrared (NIR) perfusion angiography in minimally invasive colorectal
      surgery.
AB  - BACKGROUND: Anastomotic leakage is a devastating complication of colorectal
      surgery. However, there is no technology indicative of in situ perfusion of a
      laparoscopic colorectal anastomosis. METHODS: We detail the use of near-infrared
      (NIR) laparoscopy (PinPoint System, NOVADAQ, Canada) in association with
      fluorophore [indocyanine green (ICG), 2.5 mg/ml] injection in 30 consecutive
      patients who underwent elective minimally invasive colorectal resection using the
      simultaneous appearance of the cecum or distal ileum as positive control.
      RESULTS: The median (range) age of the patients was 64 (40-81) years with a
      median (range) BMI of 26.7 (20-35.5) kg/m(2). Twenty-four patients had left-sided
      resections (including six low anterior resections) and six had right-sided
      resections. Of the total, 25 operations were cancer resections and five were for
      benign disease [either diverticular strictures (n = 3) or Crohn's disease (n =
      2)]. A high-quality intraoperative ICG angiogram was achieved in 29/30 patients.
      After ICG injection, median (range) time to perfusion fluorescence was 35 (15-45)
      s. Median (range) added time for the technique was 5 (3-9) min. Anastomotic
      perfusion was documented as satisfactory in every successful case and encouraged
      avoidance of defunctioning stomas in three patients with low anastomoses. There
      were no postoperative anastomotic leaks. CONCLUSION: Perfusion angiography of
      colorectal anastomosis at the time of their laparoscopic construction is feasible
      and readily achievable with minimal added intraoperative time. Further work is
      required to determine optimum sensitivity and threshold levels for assessment of
      perfusion sufficiency, in particular with regard to anastomotic viability.

PMID- 24566745
TI  - Safety of elective laparoscopic cholecystectomy in patients on dialysis: an
      analysis of the ACS NSQIP database.
AB  - BACKGROUND: Laparoscopic cholecystectomy (LC) remains one of the most frequently
      performed surgical procedures. The safety of LC in patients with renal disease is
      unclear. The postoperative outcomes of elective LC in patients on dialysis were
      studied and risk factors associated with longer length of stay and mortality were
      sought. METHODS: Patients who underwent LC between the dates of 1 January 2007
      and 31 December 2010 at all hospitals in North America participating in the
      American College of Surgeons National Surgical Quality Improvement Project were
      reviewed. Data from 80,995 patients were collected, and the patients on dialysis
      (N = 512) were separated and compared with those of patients not on dialysis (N =
      80,483). RESULTS: Postoperative complications for patients on and not on
      dialysis, respectively, included mortality (4.1 vs. 0.2%, p < 0.001), myocardial
      infarction (0.8 vs. 0.1%, p = 0.002), pneumonia (2.3 vs. 0.4%, p < 0.001), sepsis
      (3.1 vs. 0.4%, p < 0.001), and return to operating room (4.3 vs. 1.0%, p <
      0.001). In patients on dialysis, multivariate analysis was used to identify risk
      factors, including congestive heart failure and prior cardiac surgery as
      significant independent predictors of longer length of stay and mortality.
      CONCLUSION: Patients on dialysis who undergo LC should be carefully selected due
      to the significantly higher complication and mortality rate. Several predictors
      of longer length of stay and mortality were identified that can determine which
      patients on dialysis are good candidates for LC.

PMID- 24566746
TI  - Laparoscopic resections and ENCODE-guided genomics to advance surgery and
      oncology.

PMID- 24566747
TI  - Lower rate of colonoscopic perforation: 110,785 patients of colonoscopy performed
      by colorectal surgeons in a large teaching hospital in China.
AB  - BACKGROUND: Colonoscopic perforation (CP) has a low incidence rate. However, with
      the extensive use of colonoscopy, even low incidence rates should be evaluated to
      identify and address risks. Information on CP is quite limited in China.
      OBJECTIVE: Our study aimed to determine the frequency of CP in colonoscopies
      performed by surgeons at a large teaching hospital in China over a 12-year
      period. METHODS: A retrospective review of medical records was performed for all
      patients who had CPs from 1 January 2000 to 31 December 2012. Iatrogenic
      perforations were identified mainly by abdominal X-ray or computed tomography
      scan. Follow-up information of adverse events post-colonoscopy was identified
      from the colorectal surgery database of our hospital. Patients' demographic data,
      colonoscopy procedure information, location of perforation, treatment, and
      outcome were recorded. RESULTS: A total of 110,785 diagnostic and therapeutic
      colonoscopy procedures were performed (86,800 diagnostic cases and 23,985
      therapeutic cases) within the 12-year study period. A total of 14 incidents
      (0.012%) of CP were reported (seven males and seven females), of which nine cases
      occurred during diagnostic colonoscopy (0.01%) and five after therapeutic
      colonoscopy (three polypectomy cases, one endoscopic mucosal resection, and one
      endoscopic mucosal dissection). Mean patient age was 67.14 years. One case of CP
      (7.14%) after colonoscopy polypectomy was treated using curative colonoscopy
      endoclips. Other patients underwent operations: six cases (46.15%) of primary
      repair, four cases (28.57%) of resection with anastomosis, and two cases (15.38%)
      of resection without anastomosis. No obvious perforation was found in one patient
      (7.69%). Surgeons attempted to treat one case laparoscopically but eventually
      resorted to open surgery. The postoperative course was uncomplicated in eight
      cases (57.14%) and complicated in six cases (42.86%) but without mortality.
      CONCLUSION: CP is a serious but rare complication of colonoscopy. A perforation
      risk of 0.012% was found in our study. The optimal management of CP remains
      controversial. Treatment for CP should be individualized according to the
      patient's condition, related devices, and surgical skills of endoscopists or
      surgeons. Selective measures such as colonoscopy without intravenous sedation and
      decrease of loop formation can effectively reduce rates of perforation.

PMID- 24566748
TI  - Long-term and surgical outcomes of laparoscopic surgery for gastric
      gastrointestinal stromal tumors.
AB  - BACKGROUND: Gastrointestinal stromal tumors (GISTs) are the most common
      mesenchymal neoplasms of the gastrointestinal tract. Surgical resection with a
      free margin is the gold standard treatment for these lesions. OBJECTIVE: The aim
      of this study was to evaluate the feasibility of performing laparoscopic
      resection for gastric GIST from the viewpoint of operative and long-term
      oncological outcomes. METHODS: Between 2005 and 2011, a total of 78 consecutive
      patients undergoing laparoscopic resection of gastric GISTs were enrolled in a
      retrospective single-center study. Patient and tumor characteristics, surgical
      procedures, risk classification, postoperative complications, mortality,
      recurrence, and survival time were collected from a database, and the descriptive
      statistics were estimated. RESULTS: Patients (N = 78; 32 males and 46 females)
      with a median age of 63 years (range 31-82) were evaluated. The tumors were
      located at the cardia (10.3%), upper stomach (59.0%), middle stomach (23.1), and
      lower stomach (7.7%). The mean size of the tumors was 34.7 +/- 12.1 mm. The
      laparoscopic procedures included wedge resection (92.3%), such as laparoscopy and
      endoscopy cooperative surgery (51.3%), and gastrectomy (7.7%). All cases
      exhibited a pathologically negative margin. The mean operative time was 147.5 +/-
      63.8 min, and the mean estimated amount of blood loss was 17.8 +/- 47.9 ml. The
      mean length of hospitalization was 9.4 +/- 12.8 days. The incidence of
      perioperative complications higher than grade III was 2.6%, including two cases
      of anastomotic leakage. Regarding risk classification, low, intermediate and high
      were observed in 61, 6, and 11 cases, respectively. During a mean follow-up
      period of 45.3 +/- 18.5 months, one patient experienced local recurrence in the
      omentum. Meanwhile, four patients died due to other diseases; all other patients
      survived. CONCLUSIONS: Adequate oncologic resection was achieved in all cases.
      Laparoscopic surgery is a feasible option for gastric GISTs <5 cm.

PMID- 24566749
TI  - Transvaginal specimen extraction versus conventional minilaparotomy after
      laparoscopic anterior resection for colorectal cancer: mid-term results of a case
      matched study.
AB  - BACKGROUND: Although the vagina is considered a viable route during laparoscopic
      surgery, a number of concerns have led to a need to demonstrate the safety of a
      transvaginal approach in colorectal surgery. However, the data for transvaginal
      access in left-sided colorectal cancer are extremely limited, and no study has
      compared the clinical outcomes with a conventional laparoscopic procedure.
      OBJECTIVE: We compared the clinical outcomes of totally laparoscopic anterior
      resection with transvaginal specimen extraction (TVSE) with those of the
      conventional laparoscopic approach with minilaparotomy (LAP) for anastomosis
      construction and specimen retrieval in left-sided colorectal cancer. METHODS:
      Fifty-eight patients underwent TVSE between October 2006 and July 2011 and were
      matched by age, surgery date, tumor location, and tumor stage with patients who
      underwent conventional LAP for left-sided colorectal cancer. RESULTS: Operative
      time was significantly longer in the TVSE group (149.3 +/- 39.8 vs. 131.9 +/-
      41.4 min; p = 0.023). Patients in the TVSE group experienced less pain (pain
      score 4.9 +/- 1.6 vs. 5.8 +/- 1.9; p = 0.008), shorter time to passage of flatus
      (2.2 +/- 1.1 vs. 2.7 +/- 1.2 days; p = 0.026), and higher satisfaction with the
      cosmetic results (cosmetic score 8.0 +/- 1.4 vs. 6.3 +/- 1.5; p = 0.001). More
      endolinear staplers for rectal transection were used in the LAP group (1.2 +/-
      0.5 vs. 1.1 +/- 0.2; p = 0.021). Overall morbidities were similar in both groups;
      however, three wound infections only occurred in the LAP group. After a median
      follow-up of 34.4 (range 11-60) months, no transvaginal access-site recurrence
      occurred. The 3-year disease-free survival was similar between groups (91.5 vs.
      90.8%; p = 0.746). CONCLUSIONS: Transvaginal access after totally laparoscopic
      anterior resection is safe and feasible for left-sided colorectal cancer in
      selected patients with better short-term outcomes.

PMID- 24566750
TI  - Recurrences are common after endoscopic ampullectomy for adenoma in the familial
      adenomatous polyposis (FAP) syndrome.
AB  - BACKGROUND: Endoscopic ampullectomy is increasingly performed in patients with
      familial adenomatous polyposis (FAP)-associated ampullary adenomas. We sought to
      define the procedure-associated morbidities and long-term outcomes. METHODS: We
      performed a retrospective chart review of patients with FAP who underwent
      endoscopic ampullectomy at two tertiary institutions between 1999 and 2010. The
      severity of duodenal polyposis was classified according to Spigelman's
      classification. RESULTS: Of 26 FAP patients who underwent endoscopic
      ampullectomy, 21 arose in the setting of Spigelman's stage II duodenal polyposis.
      Adverse events associated with endoscopic ampullectomy included acute
      pancreatitis (19.2%), abdominal pain (7.6%), and bleeding (3.8%). The mean
      resected adenoma size was 0.99 +/- 0.34 cm. Three adenomas (12.0%) contained foci
      of high-grade dysplasia. Follow-up data were available for 24 patients. The mean
      follow-up duration was 84.5 +/- 36.2 months. Adenoma recurrence was observed in
      14 patients (58.3%; 14/24) at a mean of 38.3 months after initial ampullectomy.
      Adenomas >=10 mm recurred more frequently than smaller adenomas (76.9 vs. 36.4%;
      p = 0.002). Positive margins were not associated with higher recurrence rates. No
      cancers were observed during long-term follow-up. Three patients underwent a
      Whipple procedure, but none was performed for a recurrent ampullary adenoma.
      CONCLUSIONS: Endoscopic ampullectomy in FAP can be performed safely. Because
      ampullary adenomas frequently recur after endoscopic ampullectomy, close
      surveillance is essential. Smaller tumors are less likely to recur, suggesting a
      benefit for early recognition of these lesions.

PMID- 24566751
TI  - Visualization of subcapsular hepatic malignancy by indocyanine-green fluorescence
      imaging during laparoscopic hepatectomy.
AB  - BACKGROUND: Although laparoscopic hepatectomy has increasingly been used to treat
      cancers in the liver, the accuracy of intraoperative diagnosis may be inferior to
      that of open surgery because the ability to visualize and palpate the liver
      surface during laparoscopy is relatively limited. Fluorescence imaging has the
      potential to provide a simple compensatory diagnostic tool for identification of
      cancers in the liver during laparoscopic hepatectomy. METHODS: In 17 patients who
      were to undergo laparoscopic hepatectomy, 0.5 mg/kg body weight of indocyanine
      green (ICG) was administered intravenously within the 2 weeks prior to surgery.
      Intraoperatively, a laparoscopic fluorescence imaging system obtained
      fluorescence images of its surfaces during mobilization of the liver. RESULTS: In
      all, 16 hepatocellular carcinomas (HCCs) and 16 liver metastases (LMs) were
      resected. Of these, laparoscopic ICG fluorescence imaging identified 12 HCCs
      (75%) and 11 LMs (69%) on the liver surfaces distributed over Couinaud's segments
      1-8, including the 17 tumors that had not been identified by visual inspections
      of normal color images. The 23 tumors that were identified by fluorescence
      imaging were located closer to the liver surfaces than another nine tumors that
      were not identified by fluorescence imaging (median [range] depth 1 [0-5] vs. 11
      [8-30] mm; p < 0.001). CONCLUSIONS: Like palpation during open hepatectomy,
      laparoscopic ICG fluorescence imaging enables real-time identification of
      subcapsular liver cancers, thus facilitating estimation of the required extent of
      hepatic mobilization and determination of the location of an appropriate hepatic
      transection line.

PMID- 24566752
TI  - Physiological characterization of ATP-citrate lyase in Aspergillus niger.
AB  - Acetyl-CoA, an important molecule in cellular metabolism, is generated in
      multiple subcellular compartments and mainly used for energy production,
      biosynthesis of a diverse set of molecules, and protein acetylation. In
      eukaryotes, cytosolic acetyl-CoA is derived mainly from the conversion of citrate
      and CoA by ATP-citrate lyase. Here, we describe the targeted deletions of acl1
      and acl2, two tandem divergently transcribed genes encoding subunits of ATP
      citrate lyase in Aspergillus niger. We show that loss of acl1 or/and acl2 results
      in a significant decrease of acetyl-CoA and citric acid levels in these mutants,
      concomitant with diminished vegetative growth, decreased pigmentation, reduced
      asexual conidiogenesis, and delayed conidial germination. Exogenous addition of
      acetate repaired the defects of acl-deficient strains in growth and conidial
      germination but not pigmentation and conidiogenesis. We demonstrate that both
      Acl1 and Acl2 subunits are required to form a functional ATP-citrate lyase in A.
      niger. First, deletion of acl1 or/and acl2 resulted in similar defects in growth
      and development. Second, enzyme activity assays revealed that loss of either acl1
      or acl2 gene resulted in loss of ATP-citrate lyase activity. Third, in vitro
      enzyme assays using bacterially expressed 6His-tagged Acl protein revealed that
      only the complex of Acl1 and Acl2 showed ATP-citrate lyase activity, no enzyme
      activities were detected with the individual protein. Fourth, EGFP-Acl1 and
      mCherry-Acl2 proteins were co-localized in the cytosol. Thus, acl1 and acl2
      coordinately modulate the cytoplasmic acetyl-CoA levels to regulate growth,
      development, and citric acid synthesis in A. niger. 

PMID- 24566753
TI  - Irisin does not mediate resistance training-induced alterations in resting
      metabolic rate.
AB  - PURPOSE: This study aimed to investigate the effects of a 6-month preventive
      resistance training program on resting metabolic rate (RMR) and its associations
      with fat-free mass (FFM) and the newly described myokine irisin as two potential
      mechanistic links between exercise training and RMR. METHODS: In a randomized
      controlled trial, 74 sedentary healthy male and female participants either
      completed 6 months of high-repetition resistance training 3 d.wk in accordance
      with the American College of Sports Medicine recommendations (RT: n = 37; 47 +/-
      7 yr; body mass index, 25.0 +/- 3.4 kg.m) or served as controls (CO: n = 37; 50
      +/- 7 yr; body mass index, 24.2 +/- 3.2 kg.m). Strength (one-repetition maximum),
      RMR (indirect calorimetry), body fat (caliper method), and serum irisin
      concentration (enzyme-linked immunosorbent assay) were measured before and after
      6 months of training. RESULTS: Training led to an increase in strength (one
      repetition maximum leg press, 16% +/- 7%; P < 0.001). RMR increased in RT (1671
      +/- 356 vs 1843 +/- 385 kcal.d, P < 0.001) but not in CO (1587 +/- 285 vs 1602 +/
      294 kcal.d, P = 0.97; group-time interaction, P < 0.01). Body weight (RT, -0.5
      +/- 2.4 kg; CO, 0.1 +/- 2.3 kg), body fat percentage (RT, -1.1% +/- 2.5%; CO, 
      0.7% +/- 2.9%), and FFM (RT, 0.4 +/- 2.1 kg; CO, 0.6 +/- 1.9 kg) did not develop
      differently between groups (group-time interaction: P = 0.29, P = 0.54, and P =
      0.59, respectively). Serum irisin concentration increased in CO (70.8 +/- 83.4
      ng.mL, P < 0.001) but not in RT (22.4 +/- 92.6 ng.mL, P = 0.67; group-time
      interaction, P < 0.01). The change in RMR was not associated with the change in
      FFM (r = -0.11, P = 0.36) or irisin (r = -0.004, P = 0.97). CONCLUSIONS:
      Preventive resistance training elicits an increase in RMR. However, in contrast
      to currently discussed hypotheses, this increase does not seem to be mediated by
      training-induced changes in FFM or circulating irisin concentration, which casts
      doubt in the meaning of irisin for human energy balance.

PMID- 24566754
TI  - Outcome of neonatal chylous effusions: what do you tell the parents? A 10-year
      experience in a community hospital.
AB  - OBJECTIVE: The aim of the study was to describe our cases of neonatal chylous
      effusions and their outcomes and attempt to identify prognostic factors that can
      aid in the counseling of parents of future patients. PATIENTS AND METHODS: A
      retrospective chart review was conducted on all patients with a diagnosis of
      chylous effusions admitted to our 16-bed community level-3 neonatal intensive
      care unit (NICU) between June 2003 and November 2013. RESULTS: A total of 10
      patients were identified: of these 10 patients, 3 survived and 6 expired. One
      patient was transferred out and was lost to follow-up. Two-thirds of the
      survivors had only one site of chylous effusion. The six mortalities were all of
      gestational age (GA) < 34 weeks; five of the six were low birth weight (LBW) and
      all six had anasarca/hydrops, two or more sites of chylous effusions, or a
      genetic syndrome/chromosomal abnormality. The incidence of chylous effusions was
      0.03% of all births and these patients constituted 0.37% of the inborn admissions
      to the NICU. CONCLUSIONS: This case series represents a large number of patients
      considering its single-center community setting. It is prudent to communicate a
      very guarded prognosis when counseling parents of neonates with chylous
      effusions. Multiple chylous effusions, hydrops, GA < 34 weeks, LBW, or an
      accompanying genetic syndrome appear to confer worse prognosis.

PMID- 24566755
TI  - Fetal fibronectin versus cervical length as predictors of preterm birth in twin
      pregnancy with or without 17-hydroxyprogesterone caproate.
AB  - OBJECTIVE: The objective of this study was to compare cervicovaginal fetal
      fibronectin (FFN) versus transvaginal sonographic cervical length as predictors
      of preterm birth in twin pregnancy and to test whether 17-hydroxyprogesterone
      caproate (17OHPc) modifies the predictive value of FFN. STUDY DESIGN: Secondary
      analysis of a randomized trial of 17OHPc versus placebo in dichorionic-diamniotic
      twins, analyzing the subset with screening FFN (N = 198) and/or cervical length
      (N = 214) at 24 to 26 weeks of gestation. RESULTS: Positive FFN was found in 7%,
      cervical length <= 25 mm in 8%, and both positive FFN and cervical length <= 25
      mm in 3%. Birth < 32, < 34, and < 37 weeks occurred in 8, 30, and 67%,
      respectively. In logistic regression analysis controlling for FFN, cervical
      length, prior preterm birth, and treatment group, positive FFN was significantly
      associated with birth < 30 and < 32 weeks (odds ratio 55.0 [95% confidence
      interval 5.2-582], 18.1 [3.3-99], respectively, p < 0.001 for both) but cervical
      length <= 25 mm was not (odds ratio 0.1 [0.002-1.6], 0.6 [0.1-4.3]). CONCLUSION:
      Positive FFN was stronger than cervical length <= 25 mm in predicting early
      preterm birth in twins, regardless of 17OHPc use. Treatment with 17OHPc did not
      appear to alter the predictive value of FFN.

PMID- 24566756
TI  - Perfusion index variability in preterm infants treated with two different natural
      surfactants for respiratory distress syndrome.
AB  - OBJECTIVE: The objective of this study was to compare the perfusion index (PI)
      variability in premature infants with respiratory distress syndrome (RDS)
      following administration of two different natural surfactant preparations. STUDY
      DESIGN: This was a prospective study on 92 preterm infants with RDS. Patients
      were randomized into two groups. Group 1 (n = 46) received beractant; Group 2 (n
      = 46) received poractant alfa. Oxygen saturation, PI, and heart rate were
      measured by Masimo Rainbow SET Radical-7 pulse oximeter (Masimo Corp., Irvine,
      CA) before and after surfactant. The effects of the two treatment regimens on PI
      and oxygenation were compared. RESULTS: Repeated doses were more needed in
      beractant group (p = 0.04). Median oxygenation index (OI) before surfactant were
      similar, but improvement in OI was more prominent at 6th hour of surfactant in
      Group 2 (p = 0.001). Both groups had similar preductal PI values before
      surfactant. PI was higher at 6th hour of surfactant in Group 2 (p = 0.001).
      Pulmonary hemorrhage, intraventricular hemorrhage, patent ductus arteriosus,
      necrotizing enterocolitis, and mortality were more frequent in infants whose PI
      values lower than 0.7 within the first 5 days of life (p = 0.001). CONCLUSION:
      Poractant alfa resulted in more prominent improvement in PI and OI. Low PI values
      measured at early postnatal period may predict poor clinical outcome in preterm
      infants with RDS.

PMID- 24566757
TI  - Genotypic and phenotypic characterization of invasive neonatal Escherichia coli
      clinical isolates.
AB  - OBJECTIVES: The objective of this study was to describe the clinical
      characteristics of neonates with Escherichia coli bacteremia and the antibiotic
      resistance pattern of the bacterial isolates. We assessed the isolates' genetic
      relatedness and virulence phenotypic characteristics in vitro. STUDY DESIGN: A
      total of 24 neonates with E. coli bacteremia were identified prospectively in a
      tertiary-care hospital. Clinical and antibiotic resistance data were
      investigated. The E. coli isolates were analyzed by multilocus sequence typing
      (MLST); the presence of the K1 capsule and their ability to invade intestinal
      epithelial cells were also assessed. RESULTS: Most newborns were very low birth
      weight infants. Overall, 75% of the isolates were ampicillin resistant and 17%
      were gentamicin and tobramycin nonsusceptible. MLST determined sequence types 95
      and 131 (ST95 and ST131) predominated, with ST131 becoming significantly more
      prevalent recently. The K1 capsule was present in 50% of the isolates. ST131
      isolates and those producing bacteremia in newborns younger than 7 days showed a
      highly invasive phenotype. CONCLUSION: Resistance to antibiotics currently used
      empirically to treat newborns is present in bacteremia-producing E. coli. Clonal
      spread among newborns of multidrug-resistant E. coli is possible; therefore,
      continued surveillance is needed. Identification of additional virulence factors
      associated with increased invasion in neonatal E. coli strains is important and
      further studies are warranted.

PMID- 24566758
TI  - Educating tomorrow's chemists.

PMID- 24566759
TI  - Surface plasmon resonance applications in clinical analysis.
AB  - In the last 20 years, surface plasmon resonance (SPR) and its advancement with
      imaging (SPRi) emerged as a suitable and reliable platform in clinical analysis
      for label-free, sensitive, and real-time monitoring of biomolecular interactions.
      Thus, we report in this review the state of the art of clinical target detection
      with SPR-based biosensors in complex matrices (e.g., serum, saliva, blood, and
      urine) as well as in standard solution when innovative approaches or advanced
      instrumentations were employed for improved detection. The principles of SPR
      based biosensors are summarized first, focusing on the physical properties of the
      transducer, on the assays design, on the immobilization chemistry, and on new
      trends for implementing system analytical performances (e.g., coupling with
      nanoparticles (NPs). Then we critically review the detection of analytes of
      interest in molecular diagnostics, such as hormones (relevant also for anti
      doping control) and biomarkers of interest in inflammatory, cancer, and heart
      failure diseases. Antibody detection is reported in relation to immune disorder
      diagnostics. Subsequently, nucleic acid targets are considered for revealing
      genetic diseases (e.g., point mutation and single nucleotides polymorphism, SNPs)
      as well as new emerging clinical markers (microRNA) and for pathogen detection.
      Finally, examples of pathogen detection by immunosensing were also analyzed. A
      parallel comparison with the reference methods was duly made, indicating the
      progress brought about by SPR technologies in clinical routine analysis.

PMID- 24566760
TI  - Ultrafast quantitation of six quinolones in water samples by second-order
      capillary electrophoresis data modeling with multivariate curve resolution
      alternating least squares.
AB  - This paper presents the development of a capillary electrophoresis method with
      diode array detector coupled to multivariate curve resolution-alternating least
      squares (MCR-ALS) to conduct the resolution and quantitation of a mixture of six
      quinolones in the presence of several unexpected components. Overlapping of time
      profiles between analytes and water matrix interferences were mathematically
      solved by data modeling with the well-known MCR-ALS algorithm. With the aim of
      overcoming the drawback originated by two compounds with similar spectra, a
      special strategy was implemented to model the complete electropherogram instead
      of dividing the data in the region as usually performed in previous works. The
      method was first applied to quantitate analytes in standard mixtures which were
      randomly prepared in ultrapure water. Then, tap water samples spiked with several
      interferences were analyzed. Recoveries between 76.7 and 125 % and limits of
      detection between 5 and 18 MUg L(-1) were achieved.

PMID- 24566761
TI  - Improving the stability and optical properties of germanane via one-step covalent
      methyl-termination.
AB  - Two-dimensional van der Waals materials have shown great promise for a variety of
      electronic, optoelectronic, sensing and energy conversion applications. Since
      almost every atom in these two-dimensional crystals is exposed to the surface,
      covalent surface termination could provide a powerful method for the controlled
      tuning of material properties. Here we demonstrate a facile, one-step metathesis
      approach that directly converts CaGe2 crystals into mm-sized crystals of methyl
      terminated germanane (GeCH3). Replacing --H termination in GeH with --CH3
      increases the band gap by ~0.1 eV to 1.7 eV, and produces band edge fluorescence
      with a quantum yield of ~0.2%, with little dependence on layer thickness.
      Furthermore, the thermal stability of GeCH3 has been increased to 250  degrees C
      compared with 75  degrees C for GeH. This one-step metathesis approach should be
      applicable for accessing new families of two-dimensional van der Waals lattices
      that feature precise organic terminations and with enhanced optoelectronic
      properties.

PMID- 24566762
TI  - Isolation and identification of enteroviruses from sewage and sewage-contaminated
      water in Lagos, Nigeria.
AB  - Studies have confirmed silent circulation of enteroviruses in the environment
      even in the absence of associated clinical conditions in the community. In this
      light, 26 samples of sewage and sewage-contaminated water serving selected high
      risk communities in Lagos Nigeria were examined between June and September 2010.
      To concentrate virus particles in the sample, 480 MUL of each sample was
      centrifuged at 3,000 rpm for 1 h at 4  degrees C. Subsequently, pellets were
      pooled, chloroform treated and further centrifuged at 1,500 rpm for 20 min at 4 
      degrees C. The water phase (concentrate) was then collected and stored at -20 
      degrees C. The concentrates were subsequently inoculated into RD and L20B cell
      lines. Recovered isolates were identified by real-time RT-PCR (rRT-PCR),
      serotyping, VP1 amplification, sequencing and phylogenetic analysis. Overall, 9
      (34.6%) of the samples showed characteristic enterovirus cytopathic effect in RD
      cell line and were subsequently confirmed by pan-enterovirus rRT-PCR. The
      isolates were further identified by serotyping to include three E7, one E11 and
      one E13 isolates whilst four isolates were untypable. Further characterisation by
      VP1 sequencing confirmed the results of serotyping and rRT-PCR for all but
      isolate E13. Also, the four previously untypable isolates were identified to
      include two E19, one E20 and one E7 by VP1 sequencing. Results of the study
      confirmed circulation of Sub-Saharan Africa-specific enterovirus clades in the
      region, provide information on their molecular epidemiology and emphasise the
      need to combine methods of identification to enhance enterovirus surveillance.

PMID- 24566764
TI  - Large genomic rearrangement of BRCA1 and BRCA2 genes in familial breast cancer
      patients in Korea.
AB  - We screened large genomic rearrangements of the BRCA1 and BRCA2 genes in Korean,
      familial breast cancer patients. Multiplex ligation-dependent probe amplification
      assay was used to identify BRCA1 and BRCA2 genomic rearrangements in 226 Korean
      familial breast cancer patients with risk factors for BRCA1 and BRCA2 mutations,
      who previously tested negative for point mutations in the two genes. We
      identified only one large deletion (c.4186-1593_4676-1465del) in BRCA1. No large
      rearrangements were found in BRCA2. Our result indicates that large genomic
      rearrangement in the BRCA1 and BRCA2 genes does not seem like a major determinant
      of breast cancer susceptibility in the Korean population. A large-scale study
      needs to validate our result in Korea. 

PMID- 24566763
TI  - Circadian melatonin rhythm and excessive daytime sleepiness in Parkinson disease.
AB  - IMPORTANCE: Diurnal fluctuations of motor and nonmotor symptoms and a high
      prevalence of sleep-wake disturbances in Parkinson disease (PD) suggest a role of
      the circadian system in the modulation of these symptoms. However, surprisingly
      little is known regarding circadian function in PD and whether circadian
      dysfunction is involved in the development of sleep-wake disturbances in PD.
      OBJECTIVE: To determine the relationship between the timing and amplitude of the
      24-hour melatonin rhythm, a marker of endogenous circadian rhythmicity, with self
      reported sleep quality, the severity of daytime sleepiness, and disease metrics.
      DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional study from January 1, 2009,
      through December 31, 2012, of 20 patients with PD receiving stable dopaminergic
      therapy and 15 age-matched control participants. Both groups underwent blood
      sampling for the measurement of serum melatonin levels at 30-minute intervals for
      24 hours under modified constant routine conditions at the Parkinson's Disease
      and Movement Disorders Center of Northwestern University. INTERVENTIONS: Twenty
      four hour monitoring of serum melatonin secretion. MAIN OUTCOMES AND MEASURES:
      Clinical and demographic data, self-reported measures of sleep quality
      (Pittsburgh Sleep Quality Index) and daytime sleepiness (Epworth Sleepiness
      Scale), and circadian markers of the melatonin rhythm, including the amplitude,
      area under the curve (AUC), and phase of the 24-hour rhythm. RESULTS: Patients
      with PD had blunted circadian rhythms of melatonin secretion compared with
      controls; the amplitude of the melatonin rhythm and the 24-hour AUC for
      circulating melatonin levels were significantly lower in PD patients (P < .001).
      Markers of the circadian phase were not significantly different between the 2
      groups. Compared with PD patients without excessive daytime sleepiness, patients
      with excessive daytime sleepiness (Epworth Sleepiness Scale score >=10) had a
      significantly lower amplitude of the melatonin rhythm and 24-hour melatonin AUC
      (P = .001). Disease duration, Unified Parkinson's Disease Rating Scale scores,
      levodopa equivalent dose, and global Pittsburgh Sleep Quality Index score in the
      PD group were not significantly related to measures of the melatonin circadian
      rhythm. CONCLUSIONS AND RELEVANCE: Circadian dysfunction may underlie excessive
      sleepiness in PD. The nature of this association needs to be explored further in
      longitudinal studies. Approaches aimed to strengthen circadian function, such as
      timed exposure to bright light and exercise, might serve as complementary
      therapies for the nonmotor manifestations of PD.

PMID- 24566765
TI  - Impact of MRI head placement on glioma response assessment.
AB  - Diagnosis of progressive disease or (partial) response during tumor treatment is
      based on manual size estimates of enhancing tumor area: an expert measures two
      perpendicular diameters of the enhancing tumor region in a single MRI slice with
      the largest enhancing area. This paper analyzes the reliability of the area
      measure with respect to head placement in the MRI scanner and compares it with 3D
      volume measures in a dataset of eight subjects (5-7 follow-up scans each) with
      high-grade glioma. We show that the manual area measure is highly sensitive to
      head position changes, with a root mean squared error of 22%, compared to volume
      estimates with less than 5% error. In our simulated study using the 2D manual
      measurements, the majority of subjects would have been incorrectly diagnosed with
      progressive disease without any true anatomical changes. These results highlight
      the urgent need for revised and more reliable response assessment criteria, for
      example, based on increased slice resolution, 3D volume analysis and percent
      change computation with respect to an average of patient specific longitudinal
      measurements instead of a single measurement to define progression or response.

PMID- 24566766
TI  - Exploring the benefits and challenges of establishing a DRI-like process for
      bioactives.
AB  - Bioactives can be defined as: "Constituents in foods or dietary supplements,
      other than those needed to meet basic human nutritional needs, which are
      responsible for changes in health status" (Office of Disease Prevention and
      Health Promotion, Office of Public Health and Science, Department of Health and
      Human Services in Fed Reg 69:55821-55822, 2004). Although traditional nutrients,
      such as vitamins, minerals, protein, essential fatty acids and essential amino
      acids, have dietary reference intake (DRI) values, there is no such evaluative
      process for bioactives. For certain classes of bioactives, substantial scientific
      evidence exists to validate a relationship between their intake and enhanced
      health conditions or reduced risk of disease. In addition, the study of
      bioactives and their relationship to disease risk is a growing area of research
      supported by government, academic institutions, and food and supplement
      manufacturers. Importantly, consumers are purchasing foods containing bioactives,
      yet there is no evaluative process in place to let the public know how strong the
      science is behind the benefits or the quantitative amounts needed to achieve
      these beneficial health effects. This conference, Bioactives: Qualitative
      Nutrient Reference Values for Life-stage Groups?, explored why it is important to
      have a DRI-like process for bioactives and challenges for establishing such a
      process. 

PMID- 24566769
TI  - Coordination polymers of organic polymers synthesized via photopolymerization of
      single crystals: two-dimensional hydrogen bonding layers with amazing shock
      absorbing nature.
AB  - Crystalline coordination polymers of organic polymers (CPOPs) were synthesized
      via photopolymerization of Ag(I) coordination polymers of dienes which have a
      self-templating nature due to the formation of N-H...O hydrogen bonded layers.
      The shock absorbing nature of the H-bonded layer facilitated the SCSC [2+2]
      transformation upon irradiation to produce CPOPs.

PMID- 24566768
TI  - Role of the local bone renin-angiotensin system in steroid-induced osteonecrosis
      in rabbits.
AB  - The specific pathogenesis of steroid-induced osteonecrosis (ON) is yet to be
      elucidated and until recently effective prophylactic therapies have not been
      available. The local renin-angiotensin system (RAS) exists in the bone and has an
      important role in local bone regulation. However, to the best of our knowledge,
      the interrelation between local bone RAS and steroid-induced ON is yet to be
      investigated. In the present study, 45 rabbits were injected with a single
      intramuscular dose of 20 mg/kg methylprednisolone acetate (MPA) and were
      sacrificed 1 (group A), 2 (group B) and 3 (group C) weeks subsequent to MPA
      administration (n=15 per group). Ten rabbits were used as a control group (group
      N). The presence or absence of ON in the bilateral femoral heads was examined
      histopathologically. The mRNA and protein expression of components of the RAS,
      including angiotensin II (Ang II), angiotensin converting enzyme (ACE) and Ang II
      type 1 (AT1) and Ang II type 2 (AT2) receptors, were detected in the bone.
      Significant changes in Ang II, ACE, and AT1 and AT2 receptor expression were
      observed in the bone of the rabbits in the different groups. Moreover, the
      expression of Ang II and ACE was highest one week subsequent to administration of
      the glucocorticoid methylprednisolone and the expression of the AT1 and AT2
      receptors was highest two weeks following methylprednisolone administration. ON
      occurs most significantly at three weeks following the administration of MPA in
      this animal model, thus the changes in Ang II, ACE and AT1 and AT2 receptor
      expression preceded this. The present study found that ON was strongly associated
      with the activation of the local bone RAS in rabbits.

PMID- 24566767
TI  - Oilseeds ameliorate metabolic parameters in male mice, while contained lignans
      inhibit 3T3-L1 adipocyte differentiation in vitro.
AB  - PURPOSE AND BACKGROUND: The focus was directed to the study of two of the most
      lignan-rich food sources: sesame and flaxseeds. Recent epidemiological and
      experimental evidences suggesting that these foods may improve metabolic
      functions underlying metabolic syndrome (MetS). METHODS: To characterize the
      effect of these oilseeds on metabolic functions, we conducted an experimental
      study aimed at preventing adiposity and metabolic imbalance in a mouse model of
      high-fat diet (HFD)-induced MetS. Statistical analysis was performed by two-way
      analysis of variance test followed by post hoc Bonferroni analysis. RESULTS: We
      studied the effect of the oilseeds sesame and flaxseed on metabolic parameters in
      mice on a HFD. When the HFD was integrated with 20% of sesame or flaxseed flours,
      the mice showed a decrease in body fat, already at day 15, from time 0. The size
      of the adipocytes was smaller in epididymal fat, liver steatosis was inhibited,
      and insulin sensitivity was higher in mice on the supplemented diets. The
      supplemented diets also resulted in a significant increase in the serum levels of
      the lignan metabolites enterodiol and enterolactone compared with the controls.
      The expression of genes associated with the inflammatory response, glucose
      metabolism, adipose metabolism and nuclear receptor were altered by the oilseed
      supplemented diets. Some of the most abundant lignans in these oilseeds were
      studied in 3T3-L1 preadipocyte cells and were effective in inhibiting adipocyte
      differentiation at the minimal dose of 1 nM. CONCLUSIONS: The consumption of
      sesame and flaxseed may be beneficial to decrease metabolic parameters that are
      generally altered in MetS.

PMID- 24566770
TI  - Beadex affects gastric emptying in Drosophila.

PMID- 24566773
TI  - The challenges and unresolved dilemmas of prematurity.

PMID- 24566771
TI  - High-resolution melting analysis for accurate detection of BRAF mutations: a
      systematic review and meta-analysis.
AB  - The high-resolution melting curve analysis (HRMA) might be a good alternative
      method for rapid detection of BRAF mutations. However, the accuracy of HRMA in
      detection of BRAF mutations has not been systematically evaluated. We performed a
      systematic review and meta-analysis involving 1324 samples from 14 separate
      studies. The overall sensitivity of HRMA was 0.99 (95% confidence interval (CI) =
      0.75-0.82), and the overall specificity was very high at 0.99 (95% CI = 0.94
      0.98). The values for the pooled positive likelihood ratio, negative likelihood
      ratio, and diagnostic odds ratio were 68.01 (95% CI = 25.33-182.64), 0.06 (95% CI
      = 0.03-0.11), and 1263.76 (95% CI = 393.91-4064.39), respectively. The summary
      receiver operating characteristic curve for the same data shows an area of 1.00
      and a Q* value of 0.97. The high sensitivity and specificity, simplicity, low
      cost, less labor or time and rapid turnaround make HRMA a good alternative method
      for rapid detection of BRAF mutations in the clinical practice.

PMID- 24566774
TI  - High frequency ventilation in neonatology: twenty years later.

PMID- 24566772
TI  - Is prevention a realistic goal for schizophrenia?
AB  - Over the past 2 decades, increased efforts have focused on identifying those at
      genetic or clinical risk for psychosis and promoting interventions that may alter
      the onset or trajectory of schizophrenia. We review studies published between
      2010-2013 that: (1) investigate at-risk states for psychosis in larger
      epidemiological studies; (2) identify causes of certain clinical presentations of
      the schizophrenia phenotype and (3) investigate focused and multidisciplinary
      approaches to treat early clinical symptoms. The article places these recent
      studies within the context of prior research and the concept of potential
      measures to prevent or ameliorate the onset of psychosis. 

PMID- 24566775
TI  - Correlation between the educational environment and burn-out syndrome in
      residency programs at a university hospital.
AB  - INTRODUCTION: The educational environment (EE) is related to satisfaction and
      achievement. A high prevalence of professional burnout (BO) syndrome has been
      reported in the residency. The objective of this study was to evaluate the
      correlation between EE and the presence of burnout in residency programs at a
      university hospital. POPULATION AND METHODS: Residents from five programs at
      Hospital Italiano de Buenos Aires were evaluated. The following items were
      recorded: specialty, year of residency, sex, nationality and coexistence. The
      Postgraduate Hospital Education Environment Measure (PHEEM) that evaluates
      autonomy, teaching and social support, was used to measure EE. Burnout was
      measured with the Maslach Burnout Inventory (MBI) that evaluates exhaustion,
      depersonalization, and personal accomplishment. RESULTS: Ninety two residents
      participated. The mean EE was 106.8 (more positive than negative environment).
      Out of the evaluated residents, 19.6% showed burnout. There were significant
      differences in the EE between the populations with and without burnout; mean
      values: 98.7 vs. 108.8 (p= 0.0056). A negative significant correlation was
      observed between EE and exhaustion (r= -0.24) and EE and depersonalization (r= 
      0.35) and a positive significant correlation was found between EE and personal
      accomplishment (r= 0.44). In the same sense, a greater correlation was observed
      between burnout and PHEEM autonomy subscale (r= -0.58; -0.41 and 0.46,
      respectively). CONCLUSIONS: In the residency, a significant correlation was found
      between the EE and burnout (reverse with exhaustion and depersonalization, and
      direct with personal accomplishment). This correlation had greater strength and
      the same sense for items evaluating autonomy.

PMID- 24566776
TI  - Physical exercise, energy expenditure and tobacco consumption in adolescents from
      Murcia (Spain).
AB  - INTRODUCTION: Physical and sports activity is essential for a healthy lifestyle
      and is considered a prevention factor for several harmful habits on health. The
      purpose of this study was to establish the relationship between the level of
      physical activity, energy expenditure and tobacco consumption among adolescent
      students. POPULATION AND METHODS: Adolescent students aged 14 to 17 years old
      from the province of Murcia were included. Their level of physical activity was
      assessed using the International Physical Activity Questionnaire, and smoking was
      evaluated using the Youth Risk Behavior Surveillance. RESULTS: Out of 344
      adolescents, 20.3% were overweight and 5.8%, obese. Of the total, 44.2% reported
      being active on a regular basis, while 55.8% were irregularly active or inactive.
      The level of physical exercise was higher among boys than girls. Tobacco was
      consumed by 20.3% of the sample, but no significant differences were observed
      based on sex. The highest energy expenditure from physical activity was
      positively associated with non consumption of tobacco. CONCLUSIONS: Among
      adolescents, a higher level of physical activity and a higher energy expenditure
      are positively associated with non consumption of tobacco.

PMID- 24566777
TI  - Implementation of a health-related quality of life questionnaire for children and
      adolescents with celiac disease.
AB  - INTRODUCTION: Measuring health-related quality of life inpatients with celiac
      disease allows a comprehensive approach. OBJECTIVE: To assess the implementation
      and sensitivity to change of the Argentine version of the CDDUX disease-specific
      questionnaire to measure health-related quality of life in children and
      adolescents. METHODS: Descriptive, observational, longitudinal and prospective
      study. Participants were 8 to 18 year old children and adolescents with celiac
      disease, their parents or legal guardians and their gastroenterologists. The
      CDDUX questionnaire was used to assess health-related quality of life, and
      sensitivity to change was evaluated using the variation in the score obtained on
      two different occasions and a scale of change perception from the patient's and
      his/her parent's standpoint. The questionnaire implementation was appraised using
      a strength and weakness form completed by patients, parents and
      gastroenterologists. RESULTS: The first interview was conducted among 118
      child/parent dyads who completed the CDDUX and recorded their experience; 102
      completed the questionnaire on two occasions. Total scores were higher the second
      time (p = 0.009 and 0.003, respectively). There was consistency between the
      perception of change expressed by the child/adolescent and the father/ mother,
      and the difference in the CDDUX score obtained at different consultations (p <
      0.001). Standardized effect size: 0.52 for children/adolescents, and 0.45 for
      parents. A 64% agreement was observed among the opinions of children/ adolescents
      and their parent'' opinion (kappa 0.20), and a 51% agreement was found among them
      and their gastroenterologists (kappa 0.10) in terms of change between
      consultations (better, the same, or worse).Gastroenterologists also recorded
      their experience with the CDDUX. They agreed that it was satisfactory and useful.
      CONCLUSIONS: The CDDUX questionnaire demonstrated test-retest stability and
      sensitivity to change. Different opinions were obtained regarding change in
      children/adolescents health-related quality of life, with a better agreement
      among children/adolescents and their parents than among them and their
      physicians. The CDDUX questionnaire has been accepted by children/adolescents,
      their parents and gastroenterologists.

PMID- 24566778
TI  - Epidemiology of Bordetella pertussis in a children's hospital.
AB  - INTRODUCTION: Pertussis or whooping cough continues to be a major cause of
      morbidity and mortality in infants younger than 1 year old. OBJECTIVES: To
      describe the clinical and epidemiological profile of Bordetella pertussis and to
      analyze the factors associated with confirmation by PCR and case fatality rate.
      MATERIAL AND METHODS: Prospective, cohort study conducted between December 2003
      and December 2011. The study included children seen at the Hospital de Ninos
      Ricardo Gutierrez suspected of pertussis. The factors associated with
      confirmation by PCR and the case fatality rate by relative risk (RR) with a 95%
      confidence interval were studied. RESULTS: Six hundred and twenty patients with a
      38% of positive cases (236/620) were included, 3 cases were confirmed by
      epidemiological link. Confirmed cases (239) showed a seasonal pattern from
      September through February, a median age of 3 months old, and 89% had received
      less than three vaccine doses. Eighty six percent of patients were hospitalized:
      their median length of stay was 7 days. A total of 99% of patients were eu
      trophic, 98% were immunocompetent and 17.5% required intensive care. The clinical
      presentation was analyzed in 480 patients. Of them, 38% (184) had a positive PCR
      result and their symptoms were: 96.2%, cough; 76.5%, paroxysmal cough; 57.9%
      cyanosis; 55.7%, respiratory distress; 29%, fever; 22.4%, apnea; 21.9%, vomiting
      after coughing. A multivariate analysis identified the following as independent
      predictors associated with confirmation of pertussis by PCR: paroxysmal cough (OR
      2.52: 1.50-4.22; p= 0.000) and leukocytosis upon admission >20 000 white blood
      cells/mm3 (OR 7.96: 4.82-13.17; p= 0.000); having developed fever reduced the
      chance of having a positive PCR result (OR 0.47: 0.29-0.77; p= 0.003). The case
      fatality rate for hospitalized patients was 6.8%. Leukocytosis >30 000 white
      blood cells/mm3 was a predictor of fatality (RR 6.7: 1.88-23.9; p= 0.001).
      CONCLUSIONS: Confirmed cases were mostly infants younger than 1 year old who were
      healthy before and who had not completed their primary immunization schedule.
      Paroxysmal cough and leukocytosis were associated with PCR diagnosis, while
      leukocytosis was a predictor of mortality.

PMID- 24566780
TI  - Visual design: a step towards multicultural health care.
AB  - Standing at the crossroads of anthropology, communication, industrial design and
      new technology theories, this article describes the communication challenges
      posed during hospital emergencies resulting from linguistic and cultural
      differences between health care professionals and patients. In order to overcome
      communication barriers, the proposal of a visual solution was analyzed. Likewise,
      the problem was studied based on the concepts of perception, comprehension,
      interpretation and graphic representation according to visual culture and
      semiotics theories. One hundred and ffty images showing symptoms were analyzed in
      order to identify a pluricultural iconographic code. Results enabled to develop a
      list of design criteria and create the application: "My Symptoms Translator" as
      an option to overcome verbal language barriers and cultural differences. 

PMID- 24566779
TI  - [Clinical diagnosis of Kabuki syndrome: phenotype and associated abnormalities in
      two new cases].
AB  - Kabuki syndrome is a genetic entity with multiple anomalies associated with
      intellectual disability. The clinical diagnosis is based on typical facial
      features, minor skeletal abnormalities, finger pads, and postnatal growth
      deficit. Other findings may include congenital heart disease, genitourinary
      anomalies, oral clefts, anal atresia, increased susceptibility to infections,
      autoimmune and endocrine disease and hearing loss. The objective of this paper is
      to describe two patients with clinical diagnosis of Kabuki syndrome, highlighting
      the phenotypic findings and associated malformations.

PMID- 24566781
TI  - Empathic orientation among medical students from three universities in
      Barranquilla, Colombia and one university in the Dominican Republic.
AB  - OBJECTIVE: To compare empathic orientation among medical students from three
      schools of medicine in Colombia and one in the Dominican Republic. MATERIAL AND
      METHODS: Empathic orientation of medical students was measured using the
      Jefferson Scale of Physician Empathy (JSPE), Spanish version for students (the
      "S" version) validated in Mexico and Chile, and culturally adapted to Colombia
      and the Dominican Republic. Data were compared using a three-factor analysis of
      variance (model III) and a discriminant analysis. RESULTS: No differences in
      empathic orientation were observed among courses and between sexes, but
      differences were found in schools of medicine considered as a unit in each
      studied country. CONCLUSIONS: Empathic orientation levels tend to reduce as
      courses advance. This was observed in both male and female students and in all
      schools analyzed.

PMID- 24566782
TI  - Morbidity and mortality rates for childhood cancer in Argentina: 2006-2008.
AB  - INTRODUCTION: Childhood cancer is a serious public health problem in any country
      given the large number of years of life lost in an early manner. OBJECTIVE: To
      describe morbidity and mortality rates for cancer in Argentinean children and
      adolescents younger than 15 years old in the 2006-2008 three year period. Method.
      Specific mortality rates and incidence rates per million inhabitants were
      analyzed in children and adolescents younger than 15 years old by type of tumor
      and gender. Vital statistics data were used based on the databases provided by
      the Statistics and Health Information Department of the Ministry of Health of
      Argentina and the population of 0-14 year old children estimated by the National
      Statistics and Censuses Institute of Argentina (Instituto Nacional de
      Estadisticas y Censos, INDEC). In relation to morbidity data, the information
      published by the Argentine Hospital Oncopediatric Registry (Registro
      Oncopediatrico Hospitalario Argentino, ROHA) was used. RESULTS: Mortality rate
      from malignancies was 43.8 per million (3.5% of total deaths in this age group)
      and the incidence rate was 123.7 per million. Leukemia had the highest specific
      mortality rate (14.9 per million), followed by tumors in the central nervous
      system (12.7 per million). The highest incidence rates were also registered for
      these tumors (45.2 and 15.5 per million, respectively). CONCLUSIONS: Mortality
      from malignancies accounted for 3.5% of deaths in children and adolescents
      younger than 15 years old in Argentina. Leukemia and tumors in the central
      nervous system had the highest specific mortality and incidence rates.

PMID- 24566783
TI  - [The patient-centered hospital management].

PMID- 24566784
TI  - [Implicit cognition: a factor to consider in medical education].

PMID- 24566785
TI  - Vulvovaginitis in a pediatric population: relationship among etiologic agents,
      age and Tanner staging of breast development.
AB  - INTRODUCTION: Vulvovaginitis accounts for 25% of all pediatric gynecology
      consultations. OBJECTIVE: To assess the etiology of vulvovaginitis based on age
      and Tanner staging of breast development. MATERIAL AND METHODS: Descriptive,
      cross-sectional study conducted between January 1st and December 31st, 2011.
      Patients with vulvovaginitis were assessed based on two outcome measures: age
      group (GI: 0 to 8.9 years old, GII: 9 to 15.9 years old, and GIII: 16 to 18 years
      old), and the Tanner staging of breast development (I, II-III, IV-V). Results.
      Two hundred and twenty-nine patients were included, 78 girls in the GI group, 134
      in the GII group, and 17 in the GIII group; 81 girls were classified as TI, 36 as
      TII-III, and 112 as TIV-V based on Tanner staging. Shigella and Oxyuris were the
      most commonly found etiologic agents in younger girls. Candida albicans, other
      Candida species, Gardnerella and Ureaplasma urealyticum were the germs most
      commonly observed in older patients. Oxyuris was predominant in prepubertal
      girls, while Candida albicans, in postpubertal girls. CONCLUSIONS: Hormonal
      influence was more relevant than the patient's age in terms of vulvovaginitis
      etiology.

PMID- 24566786
TI  - Human bocavirus respiratory infection in infants in Cordoba, Argentina.
AB  - It has been suggested that human bocavirus (HBoV) is related to acute respiratory
      infection (ARI) in children (prevalence: 0.9% to 33%) although clinical
      characteristics have not been clearly established yet. OBJECTIVES: To identify
      the presence of HBoV in patients with ARI hospitalized in Hospital de Ninos de
      Cordoba and describe cases without co-infection. METHOD: HBoV screening was done
      by traditional PCR. Specimens to be screened were obtained from nasal secretions
      of 222 children under 2 years of age hospitalized due to an ARI during 2011.
      Demographic, clinical and radiological data were recorded. RESULTS: Fifteen HBoV+
      patients (6.8%) were identified. Their median age was 3.5 months (range: 1-22),
      7/15 in co-infection (5 respiratory syncytial virus, 1 parainfuenza-3, 1
      Bordetella pertussis). Cases without co-infection: pneumonia 5/8, bronchiolitis
      3/8; two required intermediate care, 7/8 oxygen therapy, 7/8 bronchodilators, 6/8
      antibiotics; associated disease 1/8 (microcephalus/heart disease). CONCLUSIONS:
      HBoV was identified in 15 out of 222 children (6.8%); the diagnosis of pneumonia
      was predominant without severe cases nor complications upon discharge.

PMID- 24566787
TI  - [Severe laryngitis associated to gastroesophageal reflux].
AB  - There is a strong association between gastroesophageal reflux and
      pharyngolaryngeal reflux as factors leading to respiratory disease, manifested as
      dysphonia, wheezing, coughing, recurrent laryngitis, bronchial obstruction,
      laryngospasm and apparent life-threatening events (ALTEs). These manifestations
      can be mild or severe and may sometimes put the patient's life at risk. We
      present two cases of patients with severe laryngitis who required endotracheal
      intubation, one of which underwent tracheostomy. The diagnostic methods and their
      limitations and the patients outcomes are described. 

PMID- 24566789
TI  - [Growth hormone treatment update].
AB  - Short stature in children is a common cause for referral to pediatric
      endocrinologists, corresponding most times to normal variants of growth.
      Initially growth hormone therapy was circumscribed to children presenting growth
      hormone deficiency. Since the production of recombinant human hormone its use had
      spread to other pathologies.

PMID- 24566788
TI  - [Inadvertent adolescent pregnancy: a sentinel analysis].
AB  - A sentinel event is an unexpected occurrence involving death or serious physical
      or psychological injury, or the risk thereof.The sentinel event identified was
      undiagnosed adolescent pregnancy before the indication of potentially harmful
      treatments or diagnostic methods. The team performed a root -cause analysis where
      the following causes were identified: a) Paediatrician bias: not thinking about
      adolescent sexual behaviour, incomplete questionnaires, insufficient training in
      adolescent interviews. b) Social factors: legal issues, ambiguous contraceptive
      recommendations. c) Hospital factors: lack of guidelines for counselling
      adolescents. d) Host risk factors: cultural barriers, lack of confidence.
      Regardless of any previous negative pregnancy test results, any time that a new
      potentially harmful procedure is indicated in a fertile female patient, a test of
      pregnancy diagnosed might be performed.

PMID- 24566790
TI  - [Skin and soft tissue infections in children: consensus on diagnosis and
      treatment].
AB  - Skin and soft tissue infections are a common reason for consultation in primary
      health care centers. Data from the local epidemiology of these infections are
      rare, but Staphylococcus aureus and Streptococcus pyogenes are known to be the
      major etiologic agents. The appearance in recent years of community-originated
      strains of methicillin-resistant S. aureus and erythromycin-resistant pyogenes
      raises controversy in the choice of initial empirical treatment. This national
      consensus is for pediatricians, dermatologists, infectiologists and other health
      professionals. It is about clinical management, especially the diagnosis and
      treatment of community-originated skin and soft tissue infections in
      immunocompetent patients under the age of 19.

PMID- 24566791
TI  - [Dandy Walker malformation].

PMID- 24566792
TI  - [Mail of the Pediatrics Society of Argentina].

PMID- 24566793
TI  - [Aspiration syndrome due to laryngeal cleft in an infant].
AB  - Aspiration is the passage of food content and endogenous secretions into the
      airway. Anatomical, neuromuscular or functional anomalies are among the major
      causes. The laryngeal cleft is a rare congenital anomaly that should be
      considered in the differential diagnosis of aspiration syndrome in neonates and
      infants. The main symptoms are stridor, recurrent respiratory infections and
      cyanotic crisis, cough and choking during feeding. The diagnosis is confirmed by
      endoscopic examination. The therapeutic behaviour will depend on the extent of
      the cleft, among other factors. We describe the clinical manifestations,
      diagnostic methods and treatment of an infant with this disease, and we emphasize
      the need for recognition of swallowing disorders in children in order to
      establish an accurate diagnosis and appropriate treatment to prevent and avoid
      malnutrition as well as a severe and potentially irreversible lung compromise.

PMID- 24566794
TI  - [Congenital myotonic dystrophy in a Neonatal Intensive Care Unit: case series].
AB  - Steinert myotonic dystrophy is a multisystemic disease, autosomal dominant, with
      a wide spectrum of severity and clinical manifestations. The most severe form is
      one that manifests in the neonatal period, called congenital myotonic dystrophy.
      This condition is distinguished by overall hypotonia at birth and respiratory
      function compromise. Complications are frequent, mainly psychomotor development
      delay, growth failure, food difficulties and constipation. It is associated with
      a poor prognosis, with an overall mortality of up to 50% of severely affected
      children. We present five patients with congenital myotonic dystrophy in order to
      describe clinical manifestations, diagnosis, treatment and prognosis. Existing
      data in the literature on psychomotor development, complications and prognosis of
      survivors with congenital myotonic dystrophy are scarce. In our case studies, we
      have found significant chronic psychomotor limitations.

PMID- 24566795
TI  - [Delayed diagnosis of juvenile Huntington's diseases: case report].
AB  - Huntington's disease is a neurodegenerative disease that is clinically manifested
      as mood and personality changes, loss of cognitive functions and choreiform
      movements. The pattern of inheritance is autosomic dominant. It is due to the
      gradual expansion of a cytosine, adenine, guanine trinucleotide in a gene that
      codifies the protein Huntington. The molecular diagnosis must be performed to
      confirm the diagnosis. Genetic counseling must be carefully done due to the high
      suicide risk among these patients. We present the case of a fourteen-year-old
      male with a severe disease, poor social support and an unclear pattern of
      inheritance. 

PMID- 24566796
TI  - [Imperforate hymen as a cause of abdominal pain in adolescents: a case report].
AB  - The imperforate hymen is a congenital anomaly of the female genital development.
      This is a rare pathology with an estimated incidence of 0.1% in female newborns.
      In many cases, the diagnosis goes unnoticed until puberty, debuting with cyclical
      abdominal pain in adolescents who have not submitted menarche. Diagnosis is based
      on history and physical examination, although additional tests, especially the
      ultrasound that allows to confirm clinical diagnosis and to exclude other genital
      malformations. We report a case of a 13-year-old that was diagnosed after
      consulting several times for recurrent abdominal pain.

PMID- 24566797
TI  - [Intracardiac persistence of pericatheter fibrin sheath in a newborn: case
      report].
AB  - One of the complications related to central venous catheters is the so-called
      "fibrin sheath or sleeve", the persistence of this structure after central venous
      catheter removal is uncommon, especially within a cardiac chamber. A neonate with
      symptoms of infection and portal vein thrombosis with suspected umbilical
      catheter fragment retained in right atrium was consulted for possible removal by
      catheterization. Prior to the procedure, the echocardiography findings guided us
      to the diagnosis of persistent fibrin sheath. The procedure was discontinued and
      the patient received anticoagulant therapy and antibiotics. In our case,
      echocardiography was useful in confirming the diagnosis of retained fibrin sheath
      and rule out the presence of residual central venous catheter after its removal,
      thereby avoiding an unnecessary and invasive procedure.

PMID- 24566798
TI  - Of hammers and screws: renin-angiotensin-aldosterone system inhibition to prevent
      atrial fibrillation in patients with hypertension.

PMID- 24566800
TI  - Asymmetric transfer of sound localization learning between indistinguishable
      interaural cues.
AB  - Learning in perceptual tasks is typically highly specific to the trained stimulus
      parameters. However, can learning be specific to a stimulus parameter that is
      perceptually indistinguishable from another? We assessed this question using a
      perceived sound location task in which the perceived sound location was created
      through either an interaural time difference (ITD) cue or an interaural level
      difference (ILD) cue. We used the same transient, broadband sound (clicks) for
      both cues, and after training on one of the cues, listeners switched cue mid
      session. This allowed us to assess cue specificity or transfer when the
      subjectively unnoticed cue switch occurred. One group of listeners improved their
      ITD performance as a function of training, but deteriorated in performance when
      switching to ILD in mid training session. Another group of listeners started with
      ILD training; their improved performance level did not deteriorate as they
      switched to the ITD cue. This transfer asymmetry was not hypothesized, and we
      therefore extended our study with a second data collection. Both the training
      effect and the transfer asymmetry remained after the second data collection. Our
      results indicate (a) listeners can improve both their ITD and ILD performance for
      click sounds, extending previous findings on tones; (b) learning can be specific
      to a stimulus parameter that is indistinguishable from another, as ITD learning
      did not transfer to ILD performance; but (c) ILD learning can transfer to ITD
      performance. This transfer asymmetry may have occurred because of how ITD and ILD
      are coded in early brainstem areas. 

PMID- 24566799
TI  - Effect of imatinib as add-on therapy on echocardiographic measures of right
      ventricular function in patients with significant pulmonary arterial
      hypertension.
AB  - AIMS: Imatinib mesylate, as add-on therapy in patients with pulmonary arterial
      hypertension (PAH) who remain inadequately treated despite receiving at least two
      PAH-specific drugs, improves exercise capacity and haemodynamics. We evaluated
      whether 24 weeks of add-on therapy with imatinib compared with placebo also
      improves right ventricular (RV) function assessed by echocardiography. METHODS
      AND RESULTS: Echocardiograms were obtained at baseline, 12 weeks, and 24 weeks in
      74 patients randomized to imatinib or placebo in the Imatinib in Pulmonary
      arterial hypertension, a Randomized Efficacy Study (IMPRES) trial. Right
      ventricular function was assessed by tissue Doppler tricuspid annular peak
      systolic velocity (TA S'), tricuspid annular plane systolic excursion (TAPSE), RV
      Tei index, and RV fractional area change. Between-treatment-group differences in
      the changes from baseline to week-24 were assessed using an ANCOVA with the last
      observation carried forward. At week-24 patients randomized to imatinib
      demonstrated greater improvements in TA S' (1.6 +/- 2.3 imatinib vs. 0.5 +/- 2.4
      cm/s placebo, P = 0.007) and RV Tei index (-0.11 +/- 0.18 imatinib vs. 0.05 +/-
      0.18 placebo, P = 0.005) compared with placebo, but not in TAPSE (0.07 +/- 0.44
      imatinib vs. 0.03 +/- 0.32 cm placebo, P = 0.08). Imatinib therapy was also
      associated with significant reduction in peak tricuspid regurgitation velocity,
      increase in LV size, and improvement in LV early diastolic relaxation velocity.
      CONCLUSIONS: Among patients with advanced PAH who remain symptomatic on at least
      two PAH-specific drugs, treatment with imatinib compared with placebo is
      associated with significant improvements in echocardiographic measures of RV
      function, in addition to LV size and LV early diastolic relaxation. CLINICAL
      TRIAL REGISTRATION: NCT00902174 (Clinicaltrials.gov).

PMID- 24566801
TI  - Responses towards a dying adult group member in a wild New World monkey.
AB  - Compassionate caretaking behaviour towards dying adult group members has been
      reported as being unique to humans and chimpanzees. Here we describe in detail
      the reaction of a wild dominant male common marmoset, a neotropical primate, to
      the accidental death of the dominant female of its group. The male exhibited
      behaviours towards the dying female that resembled those of chimpanzees and
      humans. The long-term relationship between the dominant pair (which lasted at
      least 3.5 years) and their social status in the group may have contributed to the
      male's behavioural response. The male prevented young individuals from
      approaching the dying female, behaviour previously observed in chimpanzees. The
      data provide an interesting insight into compassionate caretaking behaviours in
      New World primates as well as the pair-bond systems of common marmosets. These
      are rare observations, and thus their detailed descriptions are essential if we
      are to create a comparative and enhanced understanding of human and nonhuman
      primate thanatology.

PMID- 24566804
TI  - Juglans mandshurica Maxim extracts exhibit antitumor activity on HeLa cells in
      vitro.
AB  - The present study examined the potential application of Juglans mandshurica Maxim
      extracts (HT) for cancer therapy by assessing their anti-proliferative activity,
      reduction of telomerase activity, induction of apoptosis and cell cycle arrest in
      S phase in HeLa cells. From the perspective of using HT as a herbal medicine,
      photomicroscopy and florescent microscopy techniques were utilized to
      characterize the effect of the extracts on telomerase activity and cell
      morphology. Flow cytometry was employed to study apoptosis and cell cycle of HeLa
      cells, and DNA laddering was performed. The results showed that HT inhibited cell
      proliferation and telomerase activity, induced apoptosis and caused S phase
      arrest of HeLa cells in vitro. HT inhibited HeLa cell proliferation
      significantly, and the highest inhibition rate was 83.7%. A trap-silver staining
      assay showed that HT was capable of markedly decreasing telomerase activity of
      HeLa cells and this inhibition was enhanced in a time- and dose-dependent manner.
      Results of a Hoechst 33258 staining assay showed that HeLa cells treated by HT
      induced cell death. Through DNA agarose gel electrophoresis, DNA ladders of HeLa
      cells treated with HT were observed, indicating apoptosis. In conclusion, the
      present study demonstrated that HT exhibited anti-tumor effects comprising the
      inhibition of growth and telomerase activity as well as apoptosis and cell cycle
      arrest in HeLa cells.

PMID- 24566803
TI  - Ethanol alters local cellular levels of (3alpha,5alpha)-3-hydroxypregnan-20-one
      (3alpha,5alpha-THP) independent of the adrenals in subcortical brain regions.
AB  - The neuroactive steroid (3alpha,5alpha)-3-hydroxypregnan-20-one (3alpha,5alpha
      THP or allopregnanolone) is a positive modulator of GABAA receptors synthesized
      in the brain, adrenal glands, and gonads. In rats, ethanol activates the
      hypothalamic-pituitary-adrenal axis and elevates 3alpha,5alpha-THP in plasma,
      cerebral cortex, and hippocampus. In vivo, these effects are dependent on both
      the pituitary and adrenal glands. In vitro, however, ethanol locally increases
      3alpha,5alpha-THP in hippocampal slices, in the absence of adrenal influence.
      Therefore, it is not known whether ethanol can change local brain levels of
      3alpha,5alpha-THP in vivo, independent of the adrenals. To directly address this
      controversy, we administered ethanol (2 g/kg) or saline to rats that underwent
      adrenalectomy (ADX) or received sham surgery and performed immunohistochemistry
      for 3alpha,5alpha-THP. In the medial prefrontal cortex (mPFC), ethanol increased
      3alpha,5alpha-THP after sham surgery, compared with saline controls, with no
      ethanol-induced change in 3alpha,5alpha-THP following ADX. In subcortical
      regions, 3alpha,5alpha-THP was increased independent of adrenals in the CA1
      pyramidal cell layer, dentate gyrus polymorphic layer, bed nucleus of the stria
      terminalis, and paraventricular nucleus of the hypothalamus. Furthermore, ethanol
      decreased 3alpha,5alpha-THP labeling in the nucleus accumbens shore and central
      nucleus of the amygdala, independent of the adrenal glands. These data indicate
      that ethanol dynamically regulates local 3alpha,5alpha-THP levels in several
      subcortical regions; however, the adrenal glands contribute to 3alpha,5alpha-THP
      elevations in the mPFC. Using double immunofluorescent labeling we determined
      that adrenal dependence of 3alpha,5alpha-THP induction by ethanol is not due to a
      lack of colocalization of 3alpha,5alpha-THP with the cholesterol transporters
      steroidogenic acute regulatory protein (StAR) or translocator protein (TSPO).

PMID- 24566805
TI  - Strikingly poor CD8+ T-cell immunogenicity of vaccinia virus strain MVA in BALB/c
      mice.
AB  - Vaccinia virus (VACV) strain MVA is a highly attenuated vector for vaccines that
      is being explored in clinical trials. We compared the CD8(+) T-cell
      immunogenicity of MVA with that of a virulent laboratory strain of VACV (strain
      WR) in BALB/c mice by examining epitope-specific responses as well as estimating
      the total number of activated CD8(+) T cells, irrespective of specificity. We
      found that MVA elicited total CD8(+) T-cell responses that were reduced by at
      least 20-fold compared with strain WR in BALB/c mice. In C57Bl/6 mice, we also
      found a substantial difference in immunogenicity between these VACV strains, but
      it was more modest at around fivefold. Of note, the size of responses to the
      virulent WR virus was similar in both strains of mice suggesting that BALB/c mice
      can mount robust CD8(+) T-cell responses to VACV. Although the data for total
      responses clearly showed that MVA overall is poorly immunogenic in BALB/c mice,
      we found one epitope for which strong responses were made irrespective of virus
      strain. Therefore, in the context of a vaccine, some recombinant epitopes may
      have similar immunogenicity when expressed from MVA and other strains of VACV,
      but we would expect these to be exceptions. These data show clearly the
      substantial difference in immunogenicity between MVA and virulent VACV strains
      and suggest that the impact of host genetics on responses to attenuated vaccine
      vectors like MVA requires more consideration. 

PMID- 24566806
TI  - Growing a professional network to over 3000 members in less than 4 years:
      evaluation of InspireNet, British Columbia's virtual nursing health services
      research network.
AB  - BACKGROUND: Use of Web 2.0 and social media technologies has become a new area of
      research among health professionals. Much of this work has focused on the use of
      technologies for health self-management and the ways technologies support
      communication between care providers and consumers. This paper addresses a new
      use of technology in providing a platform for health professionals to support
      professional development, increase knowledge utilization, and promote
      formal/informal professional communication. Specifically, we report on factors
      necessary to attract and sustain health professionals' use of a network designed
      to increase nurses' interest in and use of health services research and to
      support knowledge utilization activities in British Columbia, Canada. OBJECTIVE:
      "InspireNet", a virtual professional network for health professionals, is a
      living laboratory permitting documentation of when and how professionals take up
      Web 2.0 and social media. Ongoing evaluation documents our experiences in
      establishing, operating, and evaluating this network. METHODS: Overall evaluation
      methods included (1) tracking website use, (2) conducting two member surveys, and
      (3) soliciting member feedback through focus groups and interviews with those who
      participated in electronic communities of practice (eCoPs) and other
      stakeholders. These data have been used to learn about the types of support that
      seem relevant to network growth. RESULTS: Network growth exceeded all
      expectations. Members engaged with varying aspects of the network's virtual
      technologies, such as teams of professionals sharing a common interest, research
      teams conducting their work, and instructional webinars open to network members.
      Members used wikis, blogs, and discussion groups to support professional work, as
      well as a members' database with contact information and areas of interest. The
      database is accessed approximately 10 times per day. InspireNet public blog posts
      are accessed roughly 500 times each. At the time of writing, 21 research teams
      conduct their work virtually using the InspireNet platform; 10 topic-based Action
      Teams meet to address issues of mutual concern. Nursing and other health
      professionals, even those who rated themselves as computer literate, required
      significant mentoring and support in their efforts to adopt their practice to a
      virtual environment. There was a steep learning curve for professionals to learn
      to work in a virtual environment and to benefit from the available technologies.
      CONCLUSIONS: Virtual professional networks can be positioned to make a
      significant contribution to ongoing professional practice and to creating
      environments supportive of information sharing, mentoring, and learning across
      geographical boundaries. Nonetheless, creation of a Web 2.0 and social media
      platform is not sufficient, in and of itself, to attract or sustain a vibrant
      community of professionals interested in improving their practice. Essential
      support includes instruction in the use of Web-based activities and time
      management, a biweekly e-Newsletter, regular communication from leaders, and an
      annual face-to-face conference.

PMID- 24566808
TI  - Copper-catalyzed tandem oxidative cyclization of cinnamamides with benzyl
      hydrocarbons through cross-dehydrogenative coupling.
AB  - The copper-catalyzed tandem oxidative cyclization of cinnamamides with benzyl
      hydrocarbons through the direct cross-dehydrogenative coupling of sp(3) and sp(2)
      C-H bonds has been developed. Satisfactorily, ethers, alcohols and alkanes could
      also be used instead of benzyl hydrocarbons in this transformation, which allows
      rapid access to diverse dihydroquinolinones in one step. 

PMID- 24566809
TI  - [Human exposures to veterinary medicines reported to the Poisons Information
      Centre Erfurt from 2003 to 2012].
AB  - AIM OF THE STUDY: The purpose of this study was to get information on all human
      exposures to veterinary medicines (HEVM) reported to the Poisons Information
      Centre (PIC) over a 10-year period. METHODS: A retrospective analysis of all HEVM
      was undertaken and a comparison was made to all human exposures (HE) registered
      by the PIC from the beginning of 2003 to the end of 2012 according to
      frequencies, circumstances of exposure, symptom severity, age groups, and
      substances involved in HEVM. RESULTS: In total, 389 cases of HEVM with 409
      veterinary medicines were registered (0.30% of all HE, 360 monoexposures). The
      relative frequency of children and adults in HEVM (children: 52.4%, adults:
      46.0%) and all HE (children: 48.7%, adults 48.7%) was the same with significant
      (p<0.05) differences in some age subgroups. The portion of accidental exposures
      was significantly (p<0.05) higher in HEVM (83.3%) than in all exposures (59.3%),
      whereas the portion of suicidal exposures was significantly (p<0.05) lower (HEVM:
      6.4%, all exposures: 23.6%). Most frequent veterinary medicines (ATCvet) in HEVM
      were antiparasitic substances, insecticides and repellents (n=185), substances
      for the nervous system (n=48), substances for the cardiovascular system (n=35),
      and immunologicals (n=35). HEVM mostly resulted in no or mild symptoms (83.8%)
      and rarely in moderate (10/389, 2.6%) or even severe symptoms (5/389, 1.3%). In 4
      of 5 cases of HEVM with severe symptoms, veterinary surgeons used products for
      animal euthanasia (n=3) or methadone (n=1). Once, self-medication with
      anthelmintics for several days by a goatherd resulted in transient blindness.
      CONCLUSIONS: In comparison to other HE, HEVM are rare. Most accidental HEVM in
      laymen result only in none to mild symptoms. If veterinary surgeons, however,
      swallow or inject products for animal euthanasia or opioids in suicidal
      intention, severe symptoms can be expected.

PMID- 24566807
TI  - Switching from natalizumab to fingolimod in multiple sclerosis: a French
      prospective study.
AB  - IMPORTANCE: The safety and efficacy of switching from natalizumab to fingolimod
      have not yet been evaluated in a large cohort of patients with multiple sclerosis
      (MS) to our knowledge. OBJECTIVE: To collect data from patients with MS switching
      from natalizumab to fingolimod. DESIGN, SETTING, AND PARTICIPANTS: The Enquete
      Nationale sur l'Introduction du Fingolimod en Relais au Natalizumab (ENIGM)
      study, a survey-based, observational multicenter cohort study among MS tertiary
      referral centers. Participants were patients for whom a switch from natalizumab
      to fingolimod was planned. Clinical data were collected on natalizumab treatment,
      duration and management of the washout period (WP), and relapse or adverse events
      during the WP and after the initiation of fingolimod. MAIN OUTCOMES AND MEASURES:
      Occurrence of MS relapse during the WP or during a 6-month follow-up period after
      the initiation of fingolimod. RESULTS: Thirty-six French MS tertiary referral
      centers participated. In total, 333 patients with MS switched from natalizumab to
      fingolimod after a mean of 31 natalizumab infusions (female to male ratio, 2.36;
      mean age, 41 years; and Expanded Disability Status Scale score at the initiation
      of natalizumab, 3.6). Seventy-one percent were seropositive for the JC
      polyomavirus. The Expanded Disability Status Scale score remained stable for
      patients receiving natalizumab. Twenty-seven percent of patients relapsed during
      the WP. A WP shorter than 3 months was associated with a lower risk of relapse
      (odds ratio, 0.23; P = .001) and with less disease activity before natalizumab
      initiation (P = .03). Patients who stopped natalizumab because of poor tolerance
      or lack of efficacy also had a higher risk of relapse (odds ratio, 3.20; P =
      .004). Twenty percent of patients relapsed during the first 6 months of
      fingolimod therapy. Three percent stopped fingolimod for efficacy, tolerance, or
      compliance issues. In the multivariate analysis, the occurrence of relapse during
      the WP was the only significant prognostic factor for relapse during fingolimod
      therapy (odds ratio, 3.80; P = .05). CONCLUSIONS AND RELEVANCE: In this study,
      switching from natalizumab to fingolimod was associated with a risk of MS
      reactivation during the WP or shortly after fingolimod initiation. The WP should
      be shorter than 3 months.

PMID- 24566811
TI  - Needle-related ultrasound artifacts and their importance in anaesthetic practice.
AB  - Real-time ultrasound guidance for any intervention relies on visualization of
      needle advancement towards a target. Unfortunately, correct identification of the
      needle tip is not straightforward, as artifacts always distort the image. The
      ultrasonic appearance of the needle is often degraded by reverberation, comet
      tail, side-lobe, beam-width, or bayonet artifacts, which can easily confuse an
      unprepared operator. Furthermore, the typical needle image, that is, a dot or a
      straight line (out-of-plane and in-plane approaches, respectively), is also a
      result of artifacts that hide the real dimensions of the needle. Knowledge and
      correct interpretation of these artifacts is important for safe practice and is
      paramount to success when precise needle manipulation is mandatory, for example,
      when the target is small. In this review, authors discuss the most important
      needle-related artifacts and provide a physical explanation focusing on
      implications for everyday practice. Recent advances that allow increased needle
      visualization and reduction of artifacts are also discussed. 

PMID- 24566810
TI  - Fabrication of magneto-controlled moveable architecture to develop reusable
      electrochemical biosensors.
AB  - Electrochemical biosensors have been studied intensively for several decades.
      Numerous sensing concepts and related interface architectures have been
      developed. However, all such architectures suffer a trade-off: simple
      architectures favour usability, whereas complex architectures favour better
      performance. To overcome this problem, we propose a novel concept by introducing
      a magneto-controlled moveable architecture (MCMA) instead of the conventional
      surface-fixed architecture. As a model, human breast cancer cells were used in
      this study. The results showed that a detection range from 100 to 1 * 10(6) cells
      could be achieved. Moreover, the whole detection cycle, including the measurement
      and the regeneration, could be completed in only 2 min. Thus, usability and
      excellent performance can be achieved in a single biosensor. 

PMID- 24566813
TI  - Barriers to medication adherence and its relationship with outcomes in pediatric
      dialysis patients.
AB  - BACKGROUND: Medication adherence is a major factor determining outcome in
      children with chronic disease. Children with end-stage renal disease are
      challenged with requirements for renal replacement therapy in addition to
      complicated medication regimens. METHODS: We assessed barriers to medication
      adherence in 22 pediatric patients receiving chronic dialysis [63.6 %
      hemodialysis (HD), 36.4 % peritoneal dialysis (PD); age 15.9 +/- 0.7 years,
      dialysis vintage 31.6 +/- 6.5 months]. Adherence was assessed by a 16-question
      survey with a maximum score (difficulty) of 64. RESULTS: The overall mean
      adherence score was 30.9 +/- 2.4 (range 16-49; median  27.5). There was a trend
      for lower adherence scores in patients on HD (27.5 +/- 2.9) compared to those on
      PD (36.8 +/- 3.7) (p = 0.06). Compared to HD patients, the mean score/question
      was significantly higher in PD patients (1.7 +/- 0.2 vs. 2.4 +/- 0.2,
      respectively; p = 0.006). Of the 16 questions, HD and PD patients gave a mean
      response of <=1.2 for five and zero questions, respectively. Neither gender, age
      nor dialysis vintage was related to adherence scores. There was also a trend for
      adherence scores to be higher in females (35.6 +/- 3.7) than in males (27.5 +/-
      2.9) (p = 0.1), but this difference did not reach statistical significance.
      Markers of mineral bone disease were similar in HD and PD patients. Among all
      targets in HD and PD patients combined, there was no relationship between
      adherence scores and number of targets reached (r = -0.09, p = 0.7). CONCLUSION:
      There are many barriers to medication adherence in pediatric patients receiving
      dialysis. In our patient group the difficulties were more evident in patients
      receiving PD than in those receiving HD.

PMID- 24566812
TI  - The long-term complications of the inherited tubulopathies: an adult perspective.
AB  - The inherited tubulopathies are lifelong disorders and their clinical features
      and complications may present quite different challenges in adulthood from those
      in childhood. In this review we outline the pathophysiology and documented
      complications (including the late and unusual) of the monogenic tubulopathies
      from the perspective of the adult nephrologist. 

PMID- 24566815
TI  - Increasing utilization of neoadjuvant chemotherapy for muscle-invasive bladder
      cancer in the United States.
AB  - The treatment and management of advanced urothelial carcinoma of the bladder is a
      considerable therapeutic challenge. Prospective, randomized clinical trial data
      demonstrate a survival advantage for those patients who receive chemotherapy
      prior to radical cystectomy. Despite the overall survival benefits, results from
      both institutional and administrative datasets suggest that historical use of a
      neoadjuvant chemotherapy paradigm is remarkably low. This review will evaluate
      the recent trends in pre-operative chemotherapy utilization that suggest small,
      but progressively increased use-currently on the order of 20 % of radical
      cystectomy patients. Additionally, this analysis will explore the various
      processes and structural barriers that preclude its receipt such as patient age
      and comorbidity, as well as physician preference, delay to potentially curable
      surgery, geographic region, distance to treatment facility, and socioeconomic
      status.

PMID- 24566814
TI  - Rosiglitazone synergizes the neuroprotective effects of valproic acid against
      quinolinic acid-induced neurotoxicity in rats: targeting PPARgamma and HDAC
      pathways.
AB  - Huntington's disease (HD) is an autosomal dominant progressive neurodegenerative
      disorder which affects medium spiny GABAergic neurons mainly in the striatum.
      Oxidative damage, neuro-inflammation, apoptosis, protein aggregation, and
      signaling of neurotrophic factors are some of the common cellular pathways
      involved in HD. Quinolinic acid (QA) causes excitotoxicity by stimulating N
      methyl-D-aspartate receptors via calcium overload leading to neurodegeneration.
      Neuroprotective potential of peroxisome proliferator activated receptor-gamma
      (PPARgamma) agonists and histone deacetylase (HDAC) inhibitors have been well
      documented in experimental models of neurodegenerative disorders; however, their
      exact mechanisms are not clear. Therefore, present study has been designed to
      explore possible neuroprotective mechanism of valproic acid (VPA) and its
      interaction with rosiglitazone against QA induced HD-like symptoms in rats.
      Single bilateral intrastriatal QA (200 nmol/2 MUl saline) administration
      significantly caused motor incoordination, memory impairment, oxidative damage,
      mitochondrial dysfunction (complex I, II, II and IV), cellular alterations [tumor
      necrosis factor-alpha (TNF-alpha), caspase-3, brain derived neurotrophic factor,
      acetylcholinesterase], and striatal neurodegeneration as compared to sham group.
      Treatment with rosiglitazone (5, 10 mg/kg) and VPA (100, 200 mg/kg) for 21 days
      significantly attenuated these behavioral, biochemical, and cellular alterations
      as compared to control (QA 200 nmol) group. However, VPA (100 mg/kg) treatment in
      combination with rosiglitazone (5 mg/kg) for 21 days synergized their
      neuroprotective effect, which was significant as compared to their effects per se
      in QA-treated animals. The present study provides an evidence of possible
      interplay of PPARgamma agonists and HDAC inhibitors as a novel therapeutic
      strategy in the management of HD.

PMID- 24566816
TI  - Diabetes. Solving human beta-cell development--what does the mouse say?
AB  - A genetic analysis of patients with permanent neonatal diabetes mellitus has
      revealed functional conservation of transcription factors critical for beta-cell
      development in both mouse and man. This finding supports the use of mice for
      modelling human disease but also highlights the need for additional human
      specific studies of beta-cell function.

PMID- 24566818
TI  - The changing face of the hospice industry: what really matters?

PMID- 24566817
TI  - Expert consensus document: A consensus on the medical treatment of acromegaly.
AB  - In March 2013, the Acromegaly Consensus Group met to revise and update guidelines
      for the medical treatment of acromegaly. The meeting comprised experts skilled in
      the medical management of acromegaly. The group considered treatment goals
      covering biochemical, clinical and tumour volume outcomes, and the place in
      guidelines of somatostatin receptor ligands, growth hormone receptor antagonists
      and dopamine agonists, and alternative modalities for treatment including
      combination therapy and novel treatments. This document represents the
      conclusions of the workshop consensus. 

PMID- 24566819
TI  - Intravitreal injection of bevacizumab for retinopathy of prematurity.
AB  - PURPOSE: To evaluate the outcomes of intravitreal injection of bevacizumab (IVB)
      for retinopathy of prematurity (ROP). METHODS: IVB was selected to be the first
      treatment for type 1 ROP in 8 eyes (4 patients). Bevacizumab (0.25 mg/eye) was
      injected into the vitreous cavity under either general anesthesia or sedation.
      Fundus photography and fluorescein angiography were performed before the IVB. One
      infant was observed to the age of 1 year 6 months, the second to 1 year 9 months,
      the third to 1 year 10 months, and the fourth to 2 years 0 month. RESULTS: Before
      the IVB, 6 eyes (3 patients) had ROP in zone II and 2 eyes (one patient) had ROP
      in zone I. The 3 infants with ROP in zone II weighed 652, 476, and 579 g with
      gestational ages of 24, 27, and 24 weeks at birth, respectively. The infant with
      ROP in zone I weighed 972 g with a gestational age of 26 weeks at birth. IVB was
      performed at postmenstrual ages of 33-37 weeks. The IVB was effective in all eyes
      with ROP in zone II and additional treatment was not required, whereas vitreous
      hemorrhage and cataract were found at 19 weeks and 5 months after the initial IVB
      in the two eyes with ROP in zone I. These two eyes required additional IVB, laser
      photocoagulation, and surgery. CONCLUSIONS: Our findings suggest that eyes with
      type 1 ROP in zone II can be treated with IVB. Further studies are needed with a
      larger number of eyes.

PMID- 24566820
TI  - Surviving and thriving with cancer using a Web-based health behavior change
      intervention: randomized controlled trial.
AB  - BACKGROUND: Given the substantial improvements in cancer screening and cancer
      treatment in the United States, millions of adult cancer survivors live for years
      following their initial cancer diagnosis and treatment. However, latent side
      effects can occur and some symptoms can be alleviated or managed effectively via
      changes in lifestyle behaviors. OBJECTIVE: The purpose of this study was to test
      the effectiveness of a six-week Web-based multiple health behavior change program
      for adult survivors. METHODS: Participants (n=352) were recruited from oncology
      clinics, a tumor registry, as well as through online mechanisms, such as Facebook
      and the Association of Cancer Online Resources (ACOR). Cancer survivors were
      eligible if they had completed their primary cancer treatment from 4 weeks to 5
      years before enrollment. Participants were randomly assigned to the Web-based
      program or a delayed-treatment control condition. RESULTS: In total, 303
      survivors completed the follow-up survey (six months after completion of the
      baseline survey) and participants in the Web-based intervention condition had
      significantly greater reductions in insomnia and greater increases in minutes per
      week of vigorous exercise and stretching compared to controls. There were no
      significant changes in fruit and vegetable consumption or other outcomes.
      CONCLUSIONS: The Web-based intervention impacted insomnia and exercise; however,
      a majority of the sample met or exceeded national recommendations for health
      behaviors and were not suffering from depression or fatigue at baseline. Thus,
      the survivors were very healthy and well-adjusted upon entry and their ability to
      make substantial health behavior changes may have been limited. Future work is
      discussed, with emphasis placed on ways in which Web-based interventions can be
      more specifically analyzed for benefit, such as in regard to social networking.
      TRIAL REGISTRATION: Clinicaltrials.gov NCT00962494;
      http://www.clinicaltrials.gov/ct2/show/NCT00962494 (Archived by WebCite at
      http://www.webcitation.org/6NIv8Dc6Q).

PMID- 24566821
TI  - Performance of a clinical decision support system and of clinical pharmacists in
      preventing drug-drug interactions on a geriatric ward.
AB  - BACKGROUND: Drug-drug interactions (DDIs) can lead to adverse drug events and
      compromise patient safety. Two common approaches to reduce these interactions in
      hospital practice are the use of clinical decision support systems and
      interventions by clinical pharmacists. OBJECTIVE: To compare the performance of
      both approaches with the main objective of learning from one approach to improve
      the other. SETTING: Acute geriatric ward in a university hospital. METHODS:
      Prospective single-centre, cohort study of patients admitted to the geriatric
      ward. An independent pharmacist compared the clinical decision support alerts
      with the DDIs identified by clinical pharmacists and evaluated their
      interventions. Contextual factors used by the clinical pharmacists for evaluation
      of the clinical relevance were analysed. Adverse drug events related to DDIs were
      investigated and the causality was evaluated by a clinical pharmacologist based
      on validated criteria. MAIN OUTCOME MEASURE: Number of alerts, interventions and
      the acceptance rates. RESULTS: Fifty patients followed by the clinical
      pharmacists, were included. The clinical pharmacists identified 240 DDIs (median
      of 3.5 per patient) and advised a therapy change for 16 of which 13 (81.2 %) were
      accepted and three (18.8 %) were not. The decision support system generated only
      six alerts of which none were accepted by the physicians. Thirty-seven adverse
      drug events were identified for 29 patients that could be related to 55 DDIs. For
      two interactions the causality was evaluated as certain, for 31 as likely, for
      ten as possible and for 12 as unlikely. Mainly intermediate level interactions
      were related to adverse drug events. Contextual factors taken into account by the
      clinical pharmacists for evaluation of the interactions were blood pressure,
      international normalised ratio, heart rate, potassium level and glycemia.
      Additionally, the clinical pharmacists looked at individual administration
      intervals and drug sequence to determine the clinical relevance of the
      interactions. CONCLUSION: Clinical pharmacists performed better than the decision
      support system mainly because the system screened only for high level DDIs and
      because of the low specificity of the alerts. This specificity can be increased
      by including contextual factors into the logic and by defining appropriate
      screening intervals that take into account the sequence in which the drugs are
      given.

PMID- 24566824
TI  - In psoriasis, levels of hope and quality of life are linked.
AB  - Psychological resources such as hope have been suggested to positively influence
      quality of life (QoL) in chronic disorders. Here, we determined hope levels of
      psoriasis vulgaris in-patients and analyzed their relation to QoL. A total of 60
      (29 male) patients were assessed for their QoL with a generic tool (WHOQOL-BREF)
      and a skin disease-specific instrument, the Dermatology Life Quality Index
      (DLQI). Hope levels were determined by use of the Basic Hope Inventory. We found
      a positive correlation between hope and all domains of WHOQOL-BREF (physical: r =
      0.446, p = 0.000; psychological r = 0.464, p = 0.000; social r = 0.302, p =
      0.019; environmental r = 0.480, p = 0000; and global r = 0.501, p = 0.000) and a
      negative correlation with DLQI (r = -0.281, p = 0.030) indicating higher QoL in
      patients with high hope. Hope was not correlated with disease severity or
      duration. Hope may play a substantial role in preventing QoL impairment in
      psoriasis. Psychotherapeutic interventions aimed at strengthening hope could
      improve QoL in this condition. 

PMID- 24566825
TI  - BMI-1 is important in bufalin-induced apoptosis of K562 cells.
AB  - The purpose of this study was to analyze the effects of bufalin on the gene
      expression of K562 cells and on the expression of BMI-1 pathway constituents in
      K562 cell apoptosis. K562 cells were treated with bufalin, and the inhibition
      rate and apoptosis were detected by an MTT assay, flow cytometry and a microarray
      assay. BMI-1, p16INK4a and p14ARF were examined by quantitative polymerase chain
      reaction (qPCR). Bufalin induced significant changes in the gene expression of
      the K562 cells; 4296 genes were differentially expressed, 2185 were upregulated
      and 2111 were downregulated. The most upregulated genes were associated with
      transcription regulation, while the most downregulated genes were associated with
      the non-coding RNA metabolic processes and DNA repair. qPCR analysis demonstrated
      that BMI-1 was overexpressed in the K562 cells. Bufalin is able to downregulate
      BMI-1 expression levels in K562 cells prematurely and cause an increase in the
      expression levels of p16INK4a and p14ARF. Moreover, bufalin downregulated BCR/ABL
      expression levels in a time-dependent manner, and the expression of BCR/ABL was
      not associated with the upregulation or downregulation of BMI-1 expression.
      Bufalin may induce K562 cell apoptosis by downregulating BMI-1 expression levels
      and accordingly upregulating the expression levels of p16INK4a and p14ARF.
      Bufalin may also induce K562 cell apoptosis via downregulating BCR/ABL expression
      levels, and this pathway may be independent of the BMI-1 pathway.

PMID- 24566823
TI  - Cloning and expression of prostaglandin E2 receptor subtype 1 (ep 1 ) in
      Bostrichthys sinensis.
AB  - Our previous studies suggested that prostaglandin E2 (PGE2) is a putative sex
      pheromone in Chinese black sleeper Bostrichthys sinensis, a fish species that
      inhabits intertidal zones and mates and spawns inside a muddy burrow. We found
      immunoreactivities of PGE2 receptor subtypes (Ep1-3) expressed in the olfactory
      sac, but only Ep1 presented higher density of immunoreactivity in mature fish
      than that in immature fish in both sexes. To gain a better understanding of the
      underlying molecular mechanism for the detection of PGE2 in the olfactory system,
      we cloned an ep 1 cDNA from the adult olfactory sac. The open-reading frame of
      the ep 1 consisted of 1,134-bp nucleotides that encoded a 378-amino acid-long
      protein with a seven-transmembrane domain, typical for the G protein-coupled
      receptors superfamily. Expression of ep 1 mRNA was observed in all tissues
      examined, with higher levels obtained in the olfactory sacs and testes. The
      expression of ep 1 mRNA in the olfactory sacs and gonads was significantly higher
      in both sexes of mature fish than in those of immature ones. Taken together, our
      results suggested that Ep1, which is highly expressed in the olfactory sacs and
      gonads of mature fish, is important for the control of reproduction and may be
      involved in PGE2-initiated spawning behavior in B. sinensis. 

PMID- 24566822
TI  - Characterization of the Dmrt1 gene in the black rockfish Sebastes schlegeli
      revealed a remarkable sex-dimorphic expression.
AB  - The Dmrt genes encode a large family of transcription factors with a conserved
      zinc finger-like DNA-binding DM domain. The function of Dmrt1, one of the family
      members, in sexual development has been well studied in invertebrates and
      vertebrates. In the present study, the full-length cDNA of Dmrt1 was isolated
      from the testis of Sebastes schlegeli. The full-length cDNA of S. schlegeli Dmrt1
      (SsDmrt1) was 1,587 bp and contained a 189-bp 5' UTR, a 489-bp 3' UTR and a 909
      bp open reading frame, which encoded 302 amino acids with a conserved DM domain
      and an male-specific motif domain. Phylogenetic analysis showed the evolutionary
      relationships of SsDmrt1 with other known Dmrt genes in fish and tetrapods.
      Several transcriptional factor-binding sites in the 5' promoter were identified
      that might regulate SsDmrt1 expression. Quantitative real-time PCR analysis
      indicated that SsDmrt1 was expressed in all of the inspected larval developmental
      stages from 1 to 35 days after birth and that the level of expression gradually
      decreased. The expression of SsDmrt1 in adult gonads was sexually dimorphic with
      extremely high expression in the testis, but very low expression in the ovary. No
      expression was detected in other tissues. Using in situ hybridization, we
      demonstrated that SsDmrt1 was specifically expressed in the germ cells of both
      the testis and the ovary. Thus, our results suggest that SsDmrt1 may have an
      important role in the differentiation of both the testis and the ovary of S.
      schlegeli. 

PMID- 24566826
TI  - Expanding the clinical phenotype associated with ELOVL4 mutation: study of a
      large French-Canadian family with autosomal dominant spinocerebellar ataxia and
      erythrokeratodermia.
AB  - IMPORTANCE: The autosomal dominant spinocerebellar ataxias (SCAs) are a complex
      group of neurodegenerative disorders with significant genetic heterogeneity.
      Despite the identification of 20 SCA genes, the cause of the disorder in a
      significant proportion of families with SCA remains unexplained. In 1972, a
      French-Canadian family segregating a combination of SCA and erythrokeratodermia
      variabilis (EKV) in an autosomal dominant fashion was described. OBJECTIVE: To
      map and identify the causative gene in this large family with SCA and EKV using a
      combination of linkage analysis and whole-exome sequencing. DESIGN, SETTING, AND
      PARTICIPANTS: A total of 32 individuals from the family have undergone complete
      neurologic and dermatologic examinations. MAIN OUTCOMES AND MEASURES: Mutations
      in ELOVL4 have been reported in families with macular degeneration. Recently,
      homozygous mutations were found in patients with ichthyosis, spastic paraplegia,
      and severe neurodevelopmental defects. In the present study, we report on a
      heterozygote mutation in ELOVL4 in affected individuals from the family with SCA
      and EKV. The mutation segregates with a milder phenotype consisting of early
      onset patches of erythema and hyperkeratosis, as well as SCA manifesting in the
      fourth or fifth decade of life. RESULTS: We describe the mapping and the
      identification of a c.504G>C transversion in ELOVL4 resulting in the p.L168F
      substitution. We also provide clinical characterization of the phenotypes in 19
      mutation carriers. CONCLUSIONS AND RELEVANCE: We report, to our knowledge, the
      first mutation in ELOVL4 that is associated with SCA and EKV. This gene encodes a
      member of the elongase family, which is responsible for the elongation of very
      long-chain fatty acids (at least 26 carbons). These fatty acids participate in a
      wide variety of physiological functions, including skin barrier formation and
      peroxisome beta-oxidation. Overall, these results provide additional insight into
      the pathogenesis of these complex neurodegenerative disorders.

PMID- 24566827
TI  - Actinoplanes lutulentus sp. nov., isolated from mucky soil in China.
AB  - A novel actinomycete, designated strain NEAU-GRX6T, was isolated from mucky soil
      collected from a stream of Jinlong Mountain in Harbin, Heilongjiang Province,
      north China, and characterized using a polyphasic approach. The isolate formed
      irregular sporangia containing motile sporangiospores on the substrate mycelium.
      The whole-cell sugars were xylose, glucose and galactose. The predominant
      menaquinones were MK-9(H6), MK-10(H4) and MK-9(H4). The major fatty acids were
      C16:0, C15:0, C18:1omega9c, C17:1omega7c and C18:0. The phospholipids were
      diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol and
      phosphatidylinositol. The DNA G+C content was 67 mol%. 16S rRNA gene sequence
      similarity studies showed that strain NEAU-GRX6T belonged to the genus
      Actinoplanes, being most closely related to Actinoplanes palleronii IFO 14916T
      (97.80% similarity) and Actinoplanes missouriensis NBRC 102363T (97.76%).
      However, the low observed levels of DNA-DNA relatedness allowed the isolate to be
      differentiated from the above-mentioned species of the genus Actinoplanes.
      Moreover, strain NEAU-GRX6T could also be distinguished from A. palleronii IFO
      14916T and A. missouriensis NBRC 102363T by phenotypic characteristics.
      Therefore, it is proposed that strain NEAU-GRX6T represents a novel species of
      the genus Actinoplanes, for which the name Actinoplanes lutulentus sp. nov. is
      proposed. The type strain is strain NEAU-GRX6T (=CGMCC 4.7090T=DSM 45883T).

PMID- 24566828
TI  - Starmerella aceti f.a., sp. nov., an ascomycetous yeast species isolated from
      fungus garden of the leafcutter ant Acromyrmex balzani.
AB  - A novel yeast species was recovered from the fungus garden of the leaf-cutting
      ant Acromyrmex balzani (Hymenoptera: Formicidae). The growth of the novel yeast
      species is limited by its ability to metabolize only a few carbon and nitrogenous
      compounds. A remarkable characteristic of this strain is the vigorous growth in 1
      % acetic acid. Sequence analysis of the D1/D2 domains of the LSU rRNA gene showed
      that the novel species belongs to the Starmerella clade and is phenotypically and
      genetically divergent from currently recognized species in this clade. Described
      here as Starmerella aceti f.a., sp. nov., it differs by 37 nucleotide
      substitutions in the D1/D2 region from Starmerella jinningensis CBS 11864(T), the
      most closely related species. The type strain of Starmerella aceti sp. nov. is TO
      125(T) ( = CBMAI 1594(T) = CBS 13086(T)). 

PMID- 24566829
TI  - Aestuariispira insulae gen. nov., sp. nov., a lipolytic bacterium isolated from a
      tidal flat.
AB  - A Gram-stain-negative, non-motile, aerobic, curved-to-spiral-rod-shaped
      bacterium, designated AH-MY2(T), was isolated from a tidal flat on Aphae island
      in the sea to the south-west of South Korea, and its taxonomic position was
      investigated using a polyphasic taxonomic approach. Strain AH-MY2(T) grew
      optimally at 30  degrees C, at pH 7.0-8.0 and in the presence of 2.0% (w/v) NaCl.
      Neighbour-joining, maximum-likelihood and maximum-parsimony phylogenetic trees
      based on 16S rRNA gene sequences showed that strain AH-MY2(T) clustered with the
      type strain of Terasakiella pusilla and that this cluster joined the clade
      comprising the type strains of species of the genus Thalassospira. Strain AH
      MY2(T) exhibited 16S rRNA gene sequence similarity values of 90.6% to the type
      strain of Terasakiella pusilla and of less than 91.0% to the type strains of
      other species with validly published names. Strain AH-MY2(T) contained Q-10 as
      the predominant ubiquinone and C(18 : 1)omega7c as the major fatty acid. The
      major polar lipids detected in strain AH-MY2(T) were phosphatidylglycerol,
      phosphatidylethanolamine, two unidentified aminolipids and one unidentified
      glycolipid. The DNA G+C content of strain AH-MY2(T) was 56.0 mol%. The
      phylogenetic data and differential chemotaxonomic and other phenotypic properties
      revealed that strain AH-MY2(T) represented a novel genus and species within the
      family Rhodospirillaceae of the class Alphaproteobacteria, for which the name
      Aestuariispira insulae gen. nov., sp. nov. is proposed. The type strain of
      Aestuariispira insulae is AH-MY2(T) ( = KCTC 32577(T) = CECT 8488(T)).

PMID- 24566830
TI  - Macrocyclic arylopeptoids--a novel type of cyclic N-alkylated aromatic
      oligoamides forming nanotubular assemblies.
AB  - The head-to-tail conversion of linear arylopeptoids (oligomeric N-substituted
      aminomethyl benzamides) into the derived novel macrocycles has enabled the first
      X-ray structures of arylopeptoid constructs and the identification of well
      defined architectures in solution. 

PMID- 24566831
TI  - Positron acceleration in a hollow plasma channel up to TeV regime.
AB  - Nowadays, human's understanding of the fundamental physics is somehow limited by
      the energy that our high energy accelerators can afford. Up to 4 TeV protons are
      realized in the Large Hadron Collider (LHC). Leptons, such as electrons and
      positrons, however gained energies of about 100 GeV or less. Multi-TeV lepton
      accelerators are still lacking due to the relatively low acceleration gradient of
      conventional methods, which may induce unbearable cost. On the other hand,
      plasmas have shown extraordinary potential in accelerating electrons and ions,
      providing orders of magnitude higher acceleration fields of 10-100 GV/m. In such
      context, we propose a plasma-based high-energy lepton accelerator, in which a
      weakly focusing plasma structure is formed near the beam axis. The structure
      preserves the emittance of the accelerated beam and produces low radiation
      losses. Moreover, the structure allows for a considerable decrease of the witness
      energy spread at the driver depletion stage. 

PMID- 24566833
TI  - A case of successful percutaneous transluminal septal myocardial ablation for
      heart failure due to severe left ventricular outflow obstruction with
      Monckeberg's arteriosclerosis, manifested after aortic valvular replacement.
AB  - Although percutaneous transluminal septal myocardial ablation (PTSMA) has been
      the established treatment of symptomatic patients with hypertrophic obstructive
      cardiomyopathy (HOCM), the efficacy for specific HOCM is not elucidated. We
      report a successful case of PTSMA for heart failure with severe left ventricular
      outflow tract (LVOT) obstruction due to sigmoid-shaped interventricular septum
      and diffuse left ventricular hypertrophy with Monckeberg's arteriosclerosis and
      aortic valvular stenosis. While the PTSMA relieved LVOT obstruction and symptoms
      in the acute phase, the modest recurrence was confirmed 6 months later, which is
      rare in the case of idiopathic HOCM. The possible mechanisms of LVOT obstruction
      and recurrence are discussed.

PMID- 24566832
TI  - Treatment of functional motor disorders.
AB  - OPINION STATEMENT: For the treatment of functional motor disorder, we recommend a
      three-stage approach. Firstly, patients must be assessed and given an unambiguous
      diagnosis, with an explanation that helps them understand that they have a
      genuine disorder, with the potential for reversibility. A key ingredient is
      allowing the patients to describe all of their symptoms as well as their ideas
      about what may be wrong. The patient should clearly understand that the positive
      diagnosis is based on the presence of typical signs (e.g., Hoover's sign for
      paralysis, entrainment test for tremor) that, in and of themselves, indicate the
      potential for reversibility. We suggest an approach that avoids the assumption
      that psychological stressors in the patient's life are causing the symptoms. The
      symptoms themselves are often the main stressor. Insisting that there must be
      others often leads to a frustrated doctor and an angry patient. Rather, at this
      initial stage, we encourage exploration of mechanisms - e.g., triggering of
      symptoms by pain, injury, or dissociation - and a discussion of how symptoms
      manifest as "abnormal motor programs" in the nervous system.Secondly, further
      time spent exploring the diagnosis, treating comorbidity, and, in the context of
      a multidisciplinary team, experimenting with altered movements and behaviors may
      benefit some patients, without the need for more complex intervention.Thirdly,
      some patients do require more complex treatment, often with a combination of
      physical rehabilitation and psychological treatments. Hypnosis, sedation, and
      transcranial magnetic stimulation may have a role in select patients.Finally,
      although they have confidence in the diagnosis, many patients do not respond to
      treatment. Ultimately, however, patients with functional motor disorder may have
      much greater potential for recovery than health professionals often consider.

PMID- 24566834
TI  - Short- and mid-term results of balloon angioplasty for renal artery fibromuscular
      dysplasia.
AB  - This study aimed to evaluate short- and mid-term outcomes of percutaneous
      transluminal renal artery angioplasty (PTRA) in patients with symptomatic renal
      artery stenosis caused by renal artery fibromuscular dysplasia (RAFMD).
      Retrospective analysis of 22 patients with RAFMD who were performed PTRA between
      2006 and 2012. These patients underwent PTRA due to poorly controlled
      hypertension. Pre- and post-PTRA blood pressure (BP) measurements and renal
      function were evaluated. Freedom from events (restenosis, repeat intervention,
      renal failure, and recurrent hypertension) was investigated using life table
      analysis. Twenty-two patients (54.5% women, mean age 39.2 years) with 24 renal
      arteries underwent PTRA. The technical success rate was 100%. The mean systolic
      BP decreased from 155.9 +/- 14.7 to 138.3 +/- 9.41 mmHg (P = 0.00004), and the
      mean diastolic BP decreased from 99.0 +/- 11.5 to 88.0 +/- 7.19 mmHg (P =
      0.0043). Rates of freedom from recurrent or worsening hypertension, defined by
      >140 mmHg systolic BP and >90 mmHg diastolic BP, were 89.4, 89.4, 81.3, and 71.1%
      at 1, 2, 3, and 4 years, respectively. Restenosis-free rates were 90.0, 83.6,
      73.4, and 61.9%, respectively. No patient underwent repeat intervention and renal
      failure. PTRA is a durable modality for treating RAFMD with favorable short- and
      mid-term clinical outcomes.

PMID- 24566835
TI  - [Optimising the rehabilitation discharge report of the German statutory pension
      insurance: the recipients' and users' perspectives].
AB  - BACKGROUND: Given the significance of documentation and information transfer in
      the health-care system as well as new technological options, there is a need for
      continuously modifying and enhancing the pension insurance's rehabilitation
      discharge report while taking into account the benefits and expenses associated
      with it. Among the regular discharge report recipients/users are general
      practitioners, medical specialists, socio-medical consultants of the German
      pension insurance and other health-care providers and funding agencies (e. g.,
      statutory health insurance, federal labour agency), external socio-medical
      consultants, judges in charge of social legislation issues, pension insurance
      administrators, and rehabilitation quality assurance officials. In the context of
      a broader project on the optimisation of the pension insurance's rehabilitation
      discharge report, the specific needs and interests of its recipients/users as
      well as suggestions concerning the improvement of structure and content of the
      discharge report were assessed. METHOD: Discharge report recipients/users were
      asked via questionnaire to indicate how frequently they use certain information
      from the report for their work. They were also asked to state objections/areas of
      concern and sugges-tions for improvement. RESULTS: 400 recipients/users filled in
      the questionnaire. More than half of the respondents considered the discharge
      report too long. Sugges-tions for shortening the report centred on avoiding
      redundancies and including standardised response items instead of free text
      passages. User groups differed with regard to the content that should be subject
      to reductions. CONCLUSIONS: The non-representative sample notwithstanding, the
      survey's results have rendered important starting points for optimising the
      statutory pension insurance's discharge report.

PMID- 24566836
TI  - [GP medication prioritisation in older patients with multiple comorbidities
      recently discharged from hospital: a case-based bottom-up approach].
AB  - INTRODUCTION: After the hospital discharge of older patients with multiple
      morbidities, GPs are often faced with the task of prioritising the patients' drug
      regimens so as to reduce the risk of overmedication. AIM: How do GPs prioritise
      such medications in multimorbid elderly patients at the transition between
      inpatient and home care? The experience by the GPs is documented in typical case
      vignettes. METHOD: 44 GPs in Sachsen-Anhalt were recruited--they were engaged in
      focus group discussions and interviewed using semi-standardised questionnaires.
      Typical case vignettes were developed, relevant to the everyday care that elderly
      patients would typically receive from their GPs with respect to their drug
      optimisation. RESULTS: According to the results of the focus groups, the
      following issues affect GPs' decisions: drug and patient safety, their own
      competence in the health system, patient health literacy, evidence base,
      communication between secondary and primary care (and their respective influences
      on each other). When considering individual cases, patient safety, patient
      wishes, and quality of life were central. This is demonstrated by the drug
      dispositions of one exemplary case vignette. CONCLUSIONS: GPs do prioritise drug
      regimens with rational criteria. Initial problem delineation, process
      documentation and the design of a transferable product are interlinking steps in
      the development of case vignettes. Care issues of drug therapy in elderly
      patients with multiple morbidities should be investigated further with larger
      representative samples in order to clarify whether the criteria used here are
      applied contextually or consistently. Embedding case vignettes into further
      education concepts is also likely to be useful.

PMID- 24566837
TI  - [Impact of characteristics related to patients and interventions on revenues and
      costs of hospitals].
AB  - Since introduction of the German refined DRG system, the, in relation to other
      countries, relatively long hospital stay has been reduced significantly. The
      analyses presented here examine the hypothesis that only few impact factors allow
      for good hospital management and that length of stay is a performance indicator.
      The analyses were based on remuneration data of 20 German hospitals for 2007
      2009, comprising details of 963 923 patient cases, and cost data for 2007-2010.
      Using simple and multiple linear regressions, the impact of hospital length of
      stay and case-based factors on case mix index (CMI) and cost categories were
      explained. The variance of the case mix index was best explained by the length of
      hospital stay, showing an adjusted regression coefficient beta=0.488 (p<0.001),
      followed by the number of coded procedures (beta=0.35, p<0.001). Other predictors
      played a minor role. The regression coefficient was higher for conservative (non
      operative) than for surgery (operative) departments. In the regression on costs,
      the length of hospital stay explained the variance of total costs by beta=0.391
      (p<0.001), among these personnel costs of the nursing staff correlated most
      highly (beta=0.595, p<0.001). The analyses confirm the working hypothesis with
      length of stay impacting CMI and costs most significantly. Treatment effort and
      complexity level, mortality rate, patient age or gender are well discussed
      factors but their joint impact on the CMI is minor. Consequently, cockpits for
      operational length of stay management comprising key data and ratios should be
      introduced on the department level.

PMID- 24566838
TI  - [Accessibility of organ cancer centres: is there already nation-wide coverage in
      Germany?].
AB  - INTRODUCTION: For several years, health care providers and health policy have
      been establishing certified cancer treatment centres. Although certification is
      not required by law, a comprehensive and close to home medical care in certified
      centres is required for all patients with cancer. We analysed whether Germany
      already provides a spatially inclusive and comprehensive supply with certified
      centres for the most common cancers for women and men. METHODS: Based on the
      central place concept "coverage" is defined as accessibility within 30 min by car
      for over 90% of the population. Using a software-supported route searching
      procedure we calculated 30- and 60-minutes-driving time zones around all breast
      and prostate cancre centers. We aggregated the population shares of all 5 digit
      postcode areas within the defined driving time zone and compared these areas to
      those outside the radius. The results are depicted as cartographic information.
      RESULTS: Nationwide 84% of the female populations over 18 years can reach the
      next breast centre within 30 min by car. In particular in the states of
      Mecklenburg-Western Pomerania and Brandenburg several areas do not provide
      sufficient access to breast centres. Using a travel time threshold of 60 min
      leads to an accessibility rate of 99%. 56% of the male population have access to
      a prostate cancer centre within half an hour by car. Again, the biggest coverage
      problems exist especially in eastern Germany. Within a radius of 60 min, the
      accessibility of prostate cancer centres increases to 94%. CONCLUSIONS: In
      Germany, some regions do not provide a spatially inclusive and comprehensive
      supply with organ cancer centers. However, it must be remembered that
      comprehensive access to care cannot be pursued as the only goal of health policy.
      Instead, the trade-off between justice, health and patients' interests and
      economic performance and adequate funding must be considered.

PMID- 24566839
TI  - [Professional self-perception, resources, stress and job satisfaction of
      psychologists in rehabilitation centres].
AB  - OBJECTIVE: Psychologists from rehabilitation centres were surveyed about their
      current job situation. Following areas were included: (a) professional self
      perception, (b) occupational resources and stress, (c) job satisfaction. METHODS:
      A nationwide survey of psychologists of all rehabilitation centres in Germany was
      conducted. Overall, 1,461 rehabilitation centres of all specialties were
      contacted in writing, of which 623 psychologists participated in the survey. Some
      of the results can be compared with reference data from previous surveys.
      RESULTS: The professional self-perception has hardly changed over the last 10
      years. Counselling and psychotherapy in one-to-one sessions and group
      interventions still play an essential role. Overall, job satisfaction and
      resources are high. General job satisfaction can be best predicted by career
      opportunities and opportunities for qualification. CONCLUSIONS: The results of
      the study indicate which resources should be strengthened in order to enhance job
      satisfaction of psychologists in medical rehabilitation. Particular thought
      should be given to improving career opportunities for psychologists in
      rehabilitation centres.

PMID- 24566840
TI  - [Complementary and alternative medicine in the German outpatient setting: extent,
      structure and reasons for provision].
AB  - BACKGROUND: Research on complementary and alternative medicine (CAM) has mainly
      focused on CAM utilisation by patients. Fewer studies have analysed extent and
      structure of CAM provision or the reasons why physicians offer CAM as a
      therapeutic option in the outpatient setting. METHODS: A standardised
      questionnaire was developed addressing reasons and patterns of CAM provision. The
      questionnaire was sent by post to 2,396 general practitioners and specialists in
      9 selected German districts. 553 physicians participated in the survey (23%).
      RESULTS: 63% of the respondents (n=350) answered that they had provided some sort
      of CAM to their patients within a period of 12 months preceding the study. The
      most frequently provided methods were acupuncture/traditional Chinese medicine,
      herbal remedies and homeopathy. In the sample, 90% of the orthopaedists were CAM
      providers, the highest rate among the participating disciplines. Several reasons
      for offering CAM were identified: conviction of therapeutic effectiveness
      regarding the patient's situation (68%), aspects of therapeutic freedom (47%) or
      less harmful side effects than conventional therapies (34%). 6% provide CAM for
      monetary reasons. CONCLUSION: Findings suggest that the provision of CAM is
      widespread in the German outpatient setting. However, it has to be taken into
      account that a selection bias may apply which may lead to an overestimation of
      CAM provision. Doctors' reasons to offer CAM are manifold; therapeutic reasons
      seem to outweigh economic motives.

PMID- 24566841
TI  - [Relevance of personal contextual factors of the ICF for use in practical social
      medicine and rehabilitation].
AB  - Personal contextual factors play an essential part in the model of the
      International Classification of Functioning, Disability and Health (ICF). The WHO
      has not yet classified personal factors for global use although they impact on
      the functioning of persons positively or negatively. In 2010, the ICF working
      group of the German Society of Social Medicine and Prevention (DGSMP) presented a
      proposal for the classification of personal factors into 72 categories previously
      arranged in 6 chapters. Now a positioning paper has been added in order to
      stimulate a discussion about the fourth component of the ICF, to contribute
      towards a broader and common understanding about the nature of personal factors
      and to incite a dialogue among all those involved in health care as well as those
      people with or with-out health problems in order to gain a comprehensive
      perspective about a person's condition.

PMID- 24566843
TI  - Answer to: letter to the editor titled Is telemedicine a worldwide trend?

PMID- 24566845
TI  - Chromosome biology: genetic reunification.

PMID- 24566844
TI  - Social media and rating sites as tools to understanding quality of care: a
      scoping review.
AB  - BACKGROUND: Insight into the quality of health care is important for any
      stakeholder including patients, professionals, and governments. In light of a
      patient-centered approach, it is essential to assess the quality of health care
      from a patient's perspective, which is commonly done with surveys or focus
      groups. Unfortunately, these "traditional" methods have significant limitations
      that include social desirability bias, a time lag between experience and
      measurement, and difficulty reaching large groups of people. Information on
      social media could be of value to overcoming these limitations, since these new
      media are easy to use and are used by the majority of the population.
      Furthermore, an increasing number of people share health care experiences online
      or rate the quality of their health care provider on physician rating sites. The
      question is whether this information is relevant to determining or predicting the
      quality of health care. OBJECTIVE: The goal of our research was to systematically
      analyze the relation between information shared on social media and quality of
      care. METHODS: We performed a scoping review with the following goals: (1) to map
      the literature on the association between social media and quality of care, (2)
      to identify different mechanisms of this relationship, and (3) to determine a
      more detailed agenda for this relatively new research area. A recognized scoping
      review methodology was used. We developed a search strategy based on four themes:
      social media, patient experience, quality, and health care. Four online
      scientific databases were searched, articles were screened, and data extracted.
      Results related to the research question were described and categorized according
      to type of social media. Furthermore, national and international stakeholders
      were consulted throughout the study, to discuss and interpret results. RESULTS:
      Twenty-nine articles were included, of which 21 were concerned with health care
      rating sites. Several studies indicate a relationship between information on
      social media and quality of health care. However, some drawbacks exist,
      especially regarding the use of rating sites. For example, since rating is
      anonymous, rating values are not risk adjusted and therefore vulnerable to fraud.
      Also, ratings are often based on only a few reviews and are predominantly
      positive. Furthermore, people providing feedback on health care via social media
      are presumably not always representative for the patient population. CONCLUSIONS:
      Social media and particularly rating sites are an interesting new source of
      information about quality of care from the patient's perspective. This new source
      should be used to complement traditional methods, since measuring quality of care
      via social media has other, but not less serious, limitations. Future research
      should explore whether social media are suitable in practice for patients, health
      insurers, and governments to help them judge the quality performance of
      professionals and organizations.

PMID- 24566842
TI  - Managing patients with psoriatic disease: the diagnosis and pharmacologic
      treatment of psoriatic arthritis in patients with psoriasis.
AB  - Psoriatic arthritis (PsA) is a chronic, systemic inflammatory disease. Up to 40 %
      of patients with psoriasis will go on to develop PsA, usually within 5-10 years
      of cutaneous disease onset. Both conditions share common pathogenic mechanisms
      involving genetic and environmental factors. Because psoriasis is typically
      present for years before PsA-related joint symptoms emerge, dermatologists are in
      a unique position to detect PsA earlier in the disease process through regular,
      routine screening of psoriasis patients. Distinguishing clinical features of PsA
      include co-occurrence of psoriatic skin lesions and nail dystrophy, as well as
      dactylitis and enthesitis. Patients with PsA are usually seronegative for
      rheumatoid factor, and radiographs may reveal unique features such as juxta
      articular new bone formation and pencil-in-cup deformity. Early treatment of PsA
      with disease-modifying anti-rheumatic drugs has the potential to slow disease
      progression and maintain patient quality of life. Optimally, a single therapeutic
      agent will control both the skin and joint psoriatic symptoms. A number of
      traditional treatments used to manage psoriasis, such as methotrexate and
      cyclosporine, are also effective for PsA, but these agents are often inadequately
      effective, temporary in benefit and associated with significant safety concerns.
      Biologic anti-tumour necrosis factor agents, such as etanercept, infliximab and
      adalimumab, are effective for treating patients who have both psoriasis and PsA.
      However, a substantial number of patients may lose efficacy, have adverse effects
      or find intravenous or subcutaneous administration inconvenient. Emerging oral
      treatments, including phosphodiesterase 4 inhibitors, such as apremilast, and new
      biologics targeting interleukin-17, such as secukinumab, brodalumab and
      ixekizumab, have shown encouraging clinical results in the treatment of psoriasis
      and/or PsA. Active and regular collaboration of dermatologists with
      rheumatologists in managing patients who have psoriasis and PsA is likely to
      yield more optimal control of psoriatic dermal and joint symptoms, and improve
      long-term patient outcomes. 

PMID- 24566846
TI  - Mung bean decreases plasma cholesterol by up-regulation of CYP7A1.
AB  - Our results affirmed that supplementation of 1 or 2% mung bean could decrease
      plasma total cholesterol and triacylglycerol level. Mung bean increased mRNA 3
      hydroxy-3-methyl-glutaryl-coenzyme A reductase. Most importantly, mung bean
      increased not only the protein level of cholesterol-7alpha-hydroxylase (CYP7A1)
      but also mRNA CYP7A1. It was concluded that the hypocholesterolemic activity of
      mung bean was most probable mediated by enhancement of bile acid excretion and up
      regulation of CYP7A1.

PMID- 24566847
TI  - Long-term results of the Ross operation: an 18-year single institutional
      experience.
AB  - OBJECTIVES: The purpose of the study was to assess the 18-year outcome of the
      Ross operation (RO), with emphasis on survival, reoperations, and late function
      of the pulmonary autografts (PAs) and the right-sided pulmonary allografts.
      METHODS: Between May 1995 to July 2013, 414 patients with a mean age (mean +/-
      standard deviation) of 30.8 +/- 13.1 years were submitted to an RO with the root
      replacement (n = 356) or the inclusion (n = 58) technique. The most prevalent
      aetiology was bicuspid valve (n = 206, 49.8%). Patients were divided in four
      groups depending on the type of allograft used on the right side. The mean follow
      up was 8.2 +/- 5.2 years and was 97.7% complete. In addition to longitudinal
      outcomes determined by means of the Kaplan-Meier analysis, log-rank test and Cox
      regression analysis were used to identify predictors of valve failure. RESULTS:
      The early mortality rate was 2.7% and the late survival rate was 89.3% at 15
      years, similar to an age- and sex-matched population. There were 22 reoperations
      on the PA (90.7% freedom at 15 years) and 15 on the pulmonary allografts (92.5%
      freedom at 15 years). The freedom rate from more than mild aortic insufficiency
      (AI) was 73.1% at 15 years. Thirty-three patients presented with a late root
      diameter >45 mm, corresponding to a freedom rate of 72.4% at 15 years. Patients
      with AI and a dilated annulus, especially males, are at greater risk for these
      complications. Among the right-sided allografts, fresh decellularized allografts
      showed significantly superior freedom from structural valve dysfunction.
      CONCLUSIONS: The RO was associated with excellent long-term survival and low
      incidence of reoperations up to 15 years. Male patients with AI and dilated
      annulus are at increased risk for late insufficiency and root dilatation. Fresh
      decellularized allografts presented the best results for reconstruction of the
      right ventricular outflow tract.

PMID- 24566848
TI  - Reoperation for neoaortic root pathology after the arterial switch operation.
AB  - OBJECTIVES: To evaluate incidence and results of surgical intervention for
      neoaortic root pathology following arterial switch operation (ASO) for
      transposition of the great arteries (TGA). METHODS: Between April 1996 and August
      2013, 12 patients underwent reoperation for neoaortic root dilatation (ARD)
      and/or neoaortic valve regurgitation (AR). Maximal aortic sinus and annulus
      diameter Z-scores were recorded. Original diagnoses were TGA/IVS (6),
      TGA/ventricular septal defect (VSD) (4) and Taussig-Bing anomaly (2) with ASO at
      a median age of 0.1 (range: 0-10.6) years. Age at ASO, VSD and complex TGA were
      reviewed as possible risk factors for reoperation. RESULTS: Twelve patients with
      tricuspid neoaortic valves underwent 15 root operations; indications were root
      dilatation (4) and root dilatation with AR (8). Median age was 18.0 (3.0-29.0)
      years at first reoperation. Median aortic root Z-score at reoperation was 6.33
      (range: 3.84-12.15). Procedures were: Bentall procedure (6), aortic valve
      replacement (2), neoaortic valve plasty (1), supracoronary tube (1) and switch
      back operation (2). Mean follow-up was 7.0 +/- 5.7 years and complete. No
      mortality occurred. One patient had two reoperations for late endocarditis.
      Technical difficulties were encountered related to specific anatomy post-ASO
      concerning coronary anatomy, poor exposure and thin-walled aorta at the site of
      pulmonary artery bifurcation after Lecompte manoeuvre. Valve sparing surgery
      seemed not feasible due to specific anatomy of the neoaortic root and valve. No
      risk factors for reoperation could be identified. CONCLUSIONS: After ASO, surgery
      for neoaortic root pathology may become necessary when follow-up is long enough
      and regardless of primary diagnosis or other risk factors. Redo neoaortic surgery
      can be performed with low risk taking into account the specific technical
      difficulties.

PMID- 24566849
TI  - Surgical management of pulmonary adenocarcinoma presenting as a pure ground-glass
      nodule.
AB  - OBJECTIVES: With recent advances in radiology, the detection of ground-glass
      nodules (GGNs) has become increasingly common. However, there still is no
      consensus on management, especially on the need for systemic lymph node (LN)
      dissection. The purpose of this study was to evaluate the surgical outcomes on
      the basis of the extent of resection of the primary lesion and mediastinal LN
      dissection and to carefully suggest appropriate treatment strategies in the
      patients with pulmonary adenocarcinoma presenting as pure ground-glass opacities.
      METHODS: From January 2006 to December 2010, 1267 patients with pulmonary
      adenocarcinoma, including adenocarcinoma in situ, underwent curative-intent
      surgical resection. Among these patients, pure GGNs were confirmed in 48 patients
      on preoperative chest computed tomography (CT) by an experienced radiologist, and
      42 underwent systemic LN dissection or sampling. We retrospectively reviewed the
      perioperative data and postoperative outcomes. RESULTS: The median age of the
      patients was 56 (range, 35-78) years, and 26 (54.2%) patients were male. The
      median size of the nodules was 12 (5-30) mm, and 8 (16.7%) had multiple lesions
      at the time of operation. The median duration between the initial diagnosis and
      operation was 4 (0-45) months. Preoperative positron emission tomography/CT was
      taken in 36 (75.0%) patients, which showed no significant metabolic uptake. For
      curative resection, lobectomy was performed in 32 (66.7%) patients, segmentectomy
      in 4, and wedge resection in 12. Clear resection margins were reported in all
      patients. Forty-two patients underwent systemic mediastinal LN dissection or
      sampling, and the median number of dissected LNs was 23 (7-53). No LN was
      reported as positive for malignancy. The median follow-up duration after the
      first operation was 39 (23-77) months, and there were no cases of late mortality,
      local recurrence or nodal recurrence. Recurrent GGNs have been developed in 6
      (12.5%) patients. CONCLUSIONS: For pure GGNs, limited resection can be performed
      when complete resection is obtained, as it was sufficient for cure and especially
      because there is high probability of multiple lesions. We were unable to
      demonstrate any additional therapeutic benefit with mediastinal LN dissection in
      patients with pure GGNs.

PMID- 24566850
TI  - Is sacrifying the phrenic nerve during thymoma resection worthwhile?
AB  - OBJECTIVES: Locally advanced thymoma can often involve the phrenic nerve (PN) due
      to its location on the mediastinal pleura. However, en bloc resection including
      the PN may cause severe postoperative complications, especially in myasthenia
      gravis patients. The aim of the study was to determine whether a PN involved
      could be spared during thymoma resection. METHODS: A retrospective study was
      conducted on patients who underwent resection of Masaoka Stage III and IV
      thymomas adherent, on digital palpation, to at least one PN in our institution
      between 1998 and 2012. An en bloc resection of the tumour with the invaded PN was
      performed unless patients with no preoperative PN paralysis had: both PN
      involved, compromised preoperative lung function, severe myasthenia gravis,
      severe comorbidities or minimal PN involvement (PN adherent to the edge of the
      tumour). All patients received postoperative radiation therapy. RESULTS: There
      were 114 patients with a mean age of 57 years (range, 28-84). PN was spared in 73
      patients (64%) and removed in 41 (36%). Sixty-five patients had Masaoka Stage III
      (57%) and 49 had Stage IV (43%); these were similar between both groups. On
      permanent histology, 6 (15%) of the resected PN were not involved, whereas a
      permanent postoperative PN palsy was found in 4 (5.4%) patients where the PN was
      spared. Postoperative mortality and morbidity were 0 and 15% in the spared group
      and 2.4 and 9.7% in the resected group, respectively (P = 0.56). Recurrence rate
      was significantly higher in the spared group (39.5 vs 19.5%; P = 0.02) but the 5
      year disease-free survival rates (53.6 vs 66.8%, P = 0.14) and overall 5-year
      survival (85 vs 88%, P = 0.6) were not significantly different between the spared
      and resected-PN groups, respectively. CONCLUSIONS: Sparing the PN during thymoma
      resection achieved good long-term and disease-free survivals in high-risk
      patients comparable with en bloc PN resection. However, it carried a higher risk
      of recurrence despite adjuvant radiation therapy.

PMID- 24566851
TI  - c-Jun transactivates Puma gene expression to promote osteoarthritis.
AB  - Osteoarthritis (OA) is a chronic degenerative joint disorder in which genetic,
      hormonal, mechanical and ageing factors affect its progression. Current studies
      are focusing on chondrocytes as a key mediator of OA at a cellular level.
      however, the mechanism underlying chondrocyte apoptosis remains unclear. PUMA is
      a pro-apoptotic member of the BH3-only subgroup of the Bcl-2 family and is
      involved in a large number of physiological and pathological processes. In the
      present study, we examined whether PUMA has a role in IL-1beta-induced apoptosis
      and whether the c-Jun N-terminal kinase (JNK)/c-Jun pathway mediates the
      induction of PUMA, thus contributing to chondrocyte apoptosis. The results
      demonstrated an increase in PUMA protein and mRNA levels in cultured mouse
      chondrocytes following 4 h of IL-1beta treatment. Furthermore, this upregulation
      of PUMA was critical for chondrocyte apoptosis as knockdown of PUMA using PUMA
      specific siRNA significantly reduced apoptosis in cultured cells. Upon
      pharmacological inhibition of the JNK/c-Jun pathway with CE11004 or SP600125, the
      expression of PUMA was notably suppressed with a concomitant decrease in
      apoptosis observed in IL-1beta-treated chondrocytes. Also, immunohistochemical
      studies revealed that the PUMA and c-Jun proteins were upregulated in
      chondrocytes from the articular cartilage of OA patients. Together, these data
      suggest a role for PUMA and the JNK/c-Jun pathway in the regulation of
      chondrocyte apoptosis during OA.

PMID- 24566852
TI  - Treating hypertension in the elderly: should the risk of falls be part of the
      equation?

PMID- 24566853
TI  - Inhibition of stearoyl-CoA desaturase-1 in differentiating 3T3-L1 preadipocytes
      upregulates elongase 6 and downregulates genes affecting triacylglycerol
      synthesis.
AB  - BACKGROUND: Stearoyl-CoA desaturase-1 (SCD1) is rate limiting for the conversion
      of saturated fatty acids palmitate (16:0) and stearate (18:0) to monounsaturated
      fatty acids palmitoleate (16:1n7) and oleate (18:1n9), respectively. Given that
      reduced SCD1 activity is associated with improved insulin sensitivity and
      decreased body weight, there is considerable interest to elucidate the role of
      this enzyme in adipocytes. During adipogenesis, SCD1 levels increase
      concomitantly with the accumulation of triacylglycerol (TG); however, the extent
      to which reduced SCD1 activity can influence TG synthesis and metabolic pathways
      in differentiating adipocytes remains relatively unexplored. OBJECTIVE: The aim
      of this work was to delineate how reduced SCD1 activity affects gene expression,
      protein content and cellular fatty acids in differentiating murine preadipocytes.
      METHODS: 3T3-L1 preadipocytes were treated with an SCD1 inhibitor (10 nM)
      throughout differentiation. After 7 days, global gene expression, protein content
      and fatty acid profiles were examined using microarrays, western blotting and gas
      chromatography, respectively. RESULTS: SCD1 inhibition increased the abundance of
      16:0 and 18:0 (45% and 194%, respectively) and decreased 16:1n7 and 18:1n7 (61%
      and 35%, respectively) in differentiated preadipocytes. Interestingly, 18:1n9
      levels increased by 61%. The augmented 18:0 suggested a possible increase in
      elongase activity. Elongase 6 (Elovl6) gene expression was increased 2.8-fold (P
      = 0.04); however, changes were not detected for ELOVL6 protein content.
      Microarray analysis revealed that genes affecting TG synthesis were downregulated
      with SCD1 inhibition, which coincided with a 33% decrease in cellular TG content.
      CONCLUSION: These results provide new mechanistic insight into the role of SCD1
      as a regulator of fatty acid profiles and TG synthesis in adipocytes, and
      reinforce that modulating SCD1 activity may help reduce the risk of obesity
      related complications.

PMID- 24566856
TI  - Regional therapies for advanced cancer.

PMID- 24566854
TI  - 4beta-Hydroxywithanolide E isolated from Physalis pruinosa calyx decreases
      inflammatory responses by inhibiting the NF-kappaB signaling in diabetic mouse
      adipose tissue.
AB  - BACKGROUND: Chronic inflammation in adipose tissue together with obesity induces
      insulin resistance. Inhibitors of chronic inflammation in adipose tissue can be a
      potent candidate for the treatment of diabetes; however, only a few compounds
      have been discovered so far. The objective of this study was to find a novel
      inhibitor that can suppress the inflammatory response in adipose tissue and to
      elucidate the intracellular signaling mechanisms of the compound. METHODS: To
      find the active compounds, we established an assay system to evaluate the
      inhibition of induced MCP-1 production in adipocyte/macrophage coculture in a
      plant extract library. The active compound was isolated by performing high
      performance liquid chromatography (HPLC) and was determined as 4beta
      hydroxywithanolide E (4betaHWE) by nuclear magnetic resonance (NMR) and mass
      spectroscopy (MS) spectral analyses. The effect of 4betaHWE on inflammation in
      adipose tissue was assessed with adipocyte culture and db/db mice. RESULTS:
      During the screening process, Physalis pruinosa calyx extract was found to
      inhibit production of MCP-1 in coculture strongly. 4betaHWE belongs to the
      withanolide family of compounds, and it has the strongest MCP-1 production
      inhibitory effect and lowest toxicity than any other withanolides in coculture.
      Its anti-inflammatory effect was partially dependent on the attenuation of NF
      kappaB signaling in adipocyte. Moreover, in vivo experiments showed that the oral
      administration of 4betaHWE to db/db mice resulted in the inhibition of macrophage
      invasion and cytokine expression in adipose tissue after 2 weeks of treatment;
      improved the plasma adiponectin, non-esterified fatty acids and MCP-1
      concentrations; and increased glucose tolerance after 3 to 4 weeks of treatment.
      CONCLUSIONS: These results suggest that 4betaHWE has anti-inflammatory effect via
      inhibition of NF-kappaB activation in adipocyte. Moreover, the attenuation of
      inflammation in adipocyte has an effect on the inhibition of macrophage
      accumulation in obese adipose tissue. Consequently, 4betaHWE improves impaired
      glucose tolerance. Thus, 4betaHWE is a useful natural anti-inflammatory compound
      to attenuate progression of diabetes and obesity.

PMID- 24566857
TI  - Prognostic significance of epithelial-mesenchymal transition of extracapsular
      spread tumors in lymph node metastases of head and neck cancer.
AB  - BACKGROUND AND PURPOSE: The extracapsular spread (ECS) of lymph node metastasis
      (LNM) reflects tumor aggressiveness and is associated with poor survival and risk
      of distant metastasis. In this study, we aimed to explore the prognostic
      significance of epithelial-mesenchymal transition (EMT) of ECS tumors in LNM of
      head and neck cancers. METHODS: We collected LNM samples from head and neck
      cancer patients (follow-up >2 years) and made 20 ECS(-): ECS(+) pairs (1:2) of
      LNM (N = 60), matched by the primary sites and by T and N classifications.
      Immunostaining of cytokeratin, E-cadherin, vimentin, and CD31 were performed and
      quantified to determine the epithelial-mesenchymal transition percent (EMT%),
      defined as vimentin(+)/cytokeratin(+) area of ECS. Univariate and multivariable
      analyses of clinic-pathologic factors, including EMT% of ECS, were conducted to
      identify the significant prognosticators. In addition, the anatomical
      relationship between CD31 vessels and ECS tumors was analyzed. RESULTS: Rather
      than the presence of ECS in LNM, higher EMT% (>50 %) of ECS strongly correlated
      with the worse overall and disease-free survival and had more frequent recurrence
      and distant dissemination in their clinical courses. ECS tumors intermingled
      closely with Ki-67(-) CD31(+) non-proliferating perinodal blood vessels.
      Particularly, vimentin(+) ECS areas exhibited a higher density of CD31(+)
      perinodal vessels than did vimentin(-) ECS. CONCLUSION: High EMT scores of ECS
      tumors in LNM predict an unfavorable prognosis and systemic dissemination more
      accurately than the simple presence of ECS in LNM in head and neck cancer
      patients.

PMID- 24566858
TI  - Atypia of undetermined significance in thyroid fine-needle aspiration cytology:
      prediction of malignancy by US and comparison of methods for further management.
AB  - BACKGROUND: Further management for thyroid nodules with cytological atypia of
      undetermined significance (AUS) has made controversial conclusions. The aim of
      this study was to evaluate the most reliable ultrasonography (US) findings to
      predict malignancy in thyroid nodules with AUS, and to compare inconclusive rates
      of repeat fine-needle aspiration (rFNA) and core needle biopsy (CNB) in nodules
      with AUS. METHODS: We retrospectively reviewed cases of thyroid nodules with AUS
      from 8,421 US-guided fine-needle aspirations in our institution between 2010 and
      2012. Nodules were confirmed either surgically or followed-up for at least 1 year
      and were compared based on nodule size, US findings, and US diagnosis to predict
      malignancy. Inconclusive rates of rFNA and CNB after initial AUS were compared.
      RESULTS: The incidence of AUS in all thyroid nodules was 3.2 % (273 of 8,421).
      Malignancies were identified in 42.1 % (64 of 152) nodules with surgery or
      sufficient follow-up. In univariate analysis, not-oval to round shape, irregular
      margin, taller-than-wide orientation, hypoechogenicity, marked hypoechogenicity,
      microcalcifications, and malignant US diagnosis were more frequent in actual
      malignancies (p < 0.05). In multivariate analysis, hypoechogenicity, marked
      hypoechogenicity, and malignant US diagnosis were significantly more frequent in
      malignancies (p < 0.05). With respect to further management of AUS, the
      inconclusive rate of CNB (17.6 %, 6/34) was significantly lower than that of rFNA
      (37.3 %; 44 of 118) (p = 0.032). CONCLUSIONS: Nodule echogenicity and US
      diagnosis can be predictive factors of malignancies for the thyroid nodules with
      cytological AUS. The CNB is more useful than rFNA for reducing the frequency of
      inconclusive results after initial AUS.

PMID- 24566855
TI  - Epigenetics and human obesity.
AB  - BACKGROUND: Recent technological advances in epigenome profiling have led to an
      increasing number of studies investigating the role of the epigenome in obesity.
      There is also evidence that environmental exposures during early life can induce
      persistent alterations in the epigenome, which may lead to an increased risk of
      obesity later in life. METHOD: This paper provides a systematic review of studies
      investigating the association between obesity and either global, site-specific or
      genome-wide methylation of DNA. Studies on the impact of pre- and postnatal
      interventions on methylation and obesity are also reviewed. We discuss
      outstanding questions, and introduce EpiSCOPE, a multidisciplinary research
      program aimed at increasing the understanding of epigenetic changes in emergence
      of obesity. RESULTS: An electronic search for relevant articles, published
      between September 2008 and September 2013 was performed. From the 319 articles
      identified, 46 studies were included and reviewed. The studies provided no
      consistent evidence for a relationship between global methylation and obesity.
      The studies did identify multiple obesity-associated differentially methylated
      sites, mainly in blood cells. Extensive, but small, alterations in methylation at
      specific sites were observed in weight loss intervention studies, and several
      associations between methylation marks at birth and later life obesity were
      found. CONCLUSIONS: Overall, significant progress has been made in the field of
      epigenetics and obesity and the first potential epigenetic markers for obesity
      that could be detected at birth have been identified. Eventually this may help in
      predicting an individual's obesity risk at a young age and opens possibilities
      for introducing targeted prevention strategies. It has also become clear that
      several epigenetic marks are modifiable, by changing the exposure in utero, but
      also by lifestyle changes in adult life, which implies that there is the
      potential for interventions to be introduced in postnatal life to modify
      unfavourable epigenomic profiles.

PMID- 24566859
TI  - Can there be a place for intraoperative salvaged blood in spine tumor surgery?
AB  - BACKGROUND: Intraoperative cell salvage (IOCS) has been used in musculoskeletal
      surgery extensively. However, it has never found its place in musculoskeletal
      oncologic surgery. We have conducted the first-ever study to evaluate the
      feasibility of IOCS in combination with a leucocyte-depletion filter (LDF) in
      metastatic spine tumor surgery. This was to pave the path for use of IOCS-LDF in
      musculoskeletal oncologic surgery. METHODS: Patients with a known primary
      epithelial tumor, who were offered surgery for metastatic spinal disease, were
      recruited. Blood samples were collected at three different stages during the
      surgery: from the operative field before IOCS processing, after IOCS processing,
      and after IOCS-LDF processing. Three separate samples (5 mL each) were taken at
      each stage. Samples were examined using immunohistochemical monoclonal antibodies
      to identify tumor cells of epithelial origin. RESULTS: Of 30 patients in the
      study, 6 were excluded for not fulfilling the inclusion criteria, leaving 24
      patients. Malignant tumor cells were detected in the samples from the operative
      field before IOCS processing in eight patients and in the samples from the
      transfusion bag after IOCS processing in three patients. No viable malignant cell
      was detectable in any of the blood samples after passage through both IOCS and
      LDF. CONCLUSIONS: The findings support the notion that the IOCS-LDF combination
      works effectively in eliminating tumor cells from salvaged blood, so this
      technique can be applied successfully in spine tumor surgery. This concept can
      then further be extended to whole musculoskeletal tumor surgery and other
      oncologic surgeries with further appropriate clinical studies.

PMID- 24566860
TI  - Identification of the sentinel node by ultrasonography in patients with breast
      cancer.
AB  - BACKGROUND: Identification of the sentinel node (SN) in patients with breast
      cancer is done by tracking a radioactive tracer, a vital dye, or both, as the
      marker(s) reach the axilla. Replacing this method with ultrasonographic (US)
      recognition of the SN could eventually spare patients the need for systemic
      anesthesia, permit minimally invasive outpatient biopsy of the node, and allow
      the formulation of a precise therapeutic plan before a definitive surgical
      procedure. METHODS: Eighty-eight axillae of 84 patients with a histologic
      diagnosis of breast cancer were studied by injecting the subareolar area of the
      affected breast(s) with technetium 99 and an iron preparation before the planned
      surgical procedure and SN biopsy. An axillary US scan was performed in all
      patients before the injection of the markers. After induction of anesthesia, the
      SN was identified, needle-localized, and extracted under US guidance.
      Confirmation that the SN was retrieved was established by concordance with the
      audible gamma signal, unless there was none. All extracted nodes had iron stains
      performed. RESULTS: All except three of the SNs were identified with US after the
      iron marker was injected, and all except six were identified by their radioactive
      signal. One of the SNs undetected on US was identified by its radioactive tracer,
      and the other two, although seen on US, had neither a gamma signal nor concordant
      iron deposits. All other SNs identified with US had a concordant audible signal
      when there was one, and all had concordant iron deposits on microscopy. Of the
      six SNs without a gamma signal, three without preincision activity were
      identified with US; three with neither a preincision nor an ex vivo signal were
      seen with US, but two of these were the SNs without a concordant iron deposit.
      CONCLUSIONS: Using an iron preparation, the SN in patients with breast cancer can
      be identified with US with an accuracy equal to and perhaps better than that
      achieved with a radioactive tracer. These findings may change the current
      diagnostic model and affect the therapeutic algorithm of breast cancer patients.

PMID- 24566861
TI  - Expressions of hypoxia-inducible factor-1 and epithelial cell adhesion molecule
      are linked with aggressive local recurrence of hepatocellular carcinoma after
      radiofrequency ablation therapy.
AB  - BACKGROUND: Radiofrequency ablation (RFA) is a widely used therapy for
      hepatocellular carcinoma (HCC). Several reports have demonstrated the aggressive
      local recurrence of HCC after RFA, suggesting that induction of further malignant
      transformation of HCC has occurred. METHODS: Eighty-eight (88) patients with HCC
      who underwent hepatic resection were included in this study. Hepatectomy was
      indicated for local recurrence of HCC after RFA (n = 10, RFA group) and for HCC
      without prior RFA (n = 78, non-RFA group). Clinicopathological data and the
      patient's prognosis after hepatectomy were compared between the two groups.
      Expression levels of hypoxia-inducible factor-1 (HIF-1), epithelial cell adhesion
      molecule (EpCAM), CD44, and vascular endothelial growth factor messenger RNA
      (mRNA) in the tumor tissues were also examined. RESULTS: The RFA group showed
      higher frequency of portal vein invasion and less tumor differentiation compared
      with the non-RFA group (p < 0.05). Overall and disease-free survival rates in the
      RFA group were significantly worse than those in the non-RFA group (p < 0.05).
      HIF-1 and EpCAM mRNA expression levels in the RFA group were significantly higher
      than those in the non-RFA group (p < 0.05). CONCLUSIONS: These results suggest
      that local HCC recurrence after RFA shows an aggressive tumor phenotype and poor
      prognosis through the enhanced expressions of HIF-1 and EpCAM in the residual HCC
      tumors after insufficient or sub-lethal treatment by RFA.

PMID- 24566862
TI  - Quality of surgery for stage III colon cancer: comparison between England,
      Germany, and Japan.
AB  - BACKGROUND: A number of studies have demonstrated that lymph node metastasis is a
      poor prognostic factor in colon cancer. Advances of surgical procedure have
      improved the outcomes of colon cancer treatment. The aim of this study was to
      compare the characteristics of surgery for stage III colon cancer between
      England, Germany, and Japan. METHODS: Using the data of patients with colon
      cancer from one English, one German, and two Japanese centers, the
      characteristics of clinicopathologic features were compared. Conventional
      surgery, complete mesocolic excision (CME) with central vascular ligation, and D3
      lymph node dissection were performed in England, Germany, and Japan,
      respectively. RESULTS: Nineteen English, 26 German, and 60 Japanese patients were
      enrolled. There was no difference in tumor location, pT, and pN factors among the
      three groups. The length of resected bowel and the area of resected mesentery of
      the English and CME specimens were significantly greater than those of the D3
      specimens (P < 0.0001 and P < 0.0001, respectively), whereas the length of the
      vascular tie to the bowel wall was similar between the CME and D3 specimens (P =
      0.87), which was longer than that of the English specimens. The number of lymph
      nodes retrieved in the CME specimens was greatest among three groups (P <
      0.0001), although the number of positive nodes was comparable (P = 0.64). The
      rates of mesocolic plane surgery in the English, CME, and D3 specimens were 47.4,
      88.5, and 71.7 %, respectively (P = 0.022). CONCLUSIONS: Three types of surgery
      for colon cancer differed in terms of the length of the resected bowel and the
      area of mesentery, although the length of the vascular tie to the bowel wall was
      similar between CME and D3 specimens. The high rates of mesocolic plane surgery
      were demonstrated in the CME and D3 specimens.

PMID- 24566863
TI  - EpCAM, a potential therapeutic target for esophageal squamous cell carcinoma.
AB  - BACKGROUND: Molecular-targeted drugs are not available for esophageal squamous
      cell carcinoma (ESCC), which has a poor prognosis. We investigated the
      clinicopathological significance of epithelial cell adhesion molecule (EpCAM)
      expression and the utility of EpCAM as a potential therapeutic target. METHODS:
      The relationship between EpCAM expression and clinicopathological factors was
      examined by immunohistochemistry in 74 patients with resectable ESCC. A total of
      ten ESCC cell lines were analyzed for EpCAM expression. The effects of EpCAM
      knockdown in TE4, TE10, and TE14 cells were examined with regard to cell
      proliferation and gene expression in vitro and tumor growth in vivo. The
      antitumor effect of catumaxomab in ESCC cell lines was examined. RESULTS: EpCAM
      overexpression was associated with poor survival in ESCC patients (P = 0.026).
      Multivariate Cox regression analysis showed that EpCAM overexpression was a
      significant and independent prognostic factor for surgically treated ESCC (P =
      0.004). TE4 and TE10 cells showed high EpCAM expression, in contrast to TE14.
      EpCAM siRNA knockdown in TE4 and TE10 cells downregulated CCND1 and CCNE2 and
      suppressed cell proliferation. Low EpCAM expression reduced tumorigenesis; TE4
      cells initiated tumorigenesis in seven of the ten mice injected, whereas shRNA
      knockdown resulted in smaller tumors in two of ten mice at 6 weeks after
      transplantation. Concentration- and time-dependent antitumor effects of
      catumaxomab were observed in TE4 and TE10 cells. CONCLUSIONS: EpCAM
      overexpression is an independent prognostic factor for surgically treated ESCC.
      EpCAM contributes to cell proliferation and tumorigenesis and may be a useful
      therapeutic target for ESCC.

PMID- 24566864
TI  - CD8+ and FOXP3+ tumor-infiltrating T cells before and after chemoradiotherapy for
      rectal cancer.
AB  - BACKGROUND: CD8+ cytotoxic T cells and forkhead box P3 (FOXP3)+ regulatory T
      cells are major players in tumor immunity. Increased CD8+ tumor-infiltrating
      lymphocytes (TILs) and high CD8/FOXP3 TIL ratios are associated with improved
      survival. Neoadjuvant chemoradiotherapy (CRT) can result in tumor regression;
      however, immunomodulation during CRT for rectal cancer has not been thoroughly
      assessed. We investigated whether neoadjuvant CRT altered the in situ immune cell
      population and clinical implications of TIL accumulation before and after CRT.
      METHODS: We recruited 93 rectal cancer patients who underwent neoadjuvant CRT and
      radical resection. Pretreatment biopsy and post-CRT resected specimens were
      immunostained for CD8 and FOXP3, and the densities of stromal (STL) and
      intraepithelial (IEL) immunopositive TILs were determined separately. In
      addition, 54 patients with resections but without neoadjuvant CRT were enrolled
      for comparison. RESULTS: CD8+ STL density doubled after CRT (average counts: 92
      vs. 230 per microscopic field using a 20 * objective lens; P < 0.0001), whereas
      FOXP3+ STL counts remained stable (109 vs. 109). Compared with non-CRT cases, CRT
      increased CD8+ STL density. Multivariate analyses demonstrated that high post-CRT
      CD8 + STL density was associated with better prognosis (5-year recurrence-free
      survival: 87.5 vs. 57.8 %; P = 0.0058) and that a high pretreatment CD8/FOXP3 IEL
      ratio was a predictor of favorable tumor regression (P = 0.0029). CONCLUSIONS:
      Favorable anticancer immunity occurred after CRT for rectal cancer by altering
      TIL subsets. A high CD8/FOXP3 IEL ratio before CRT and a high CD8+ STL density
      after CRT were associated with a favorable clinical outcome.

PMID- 24566865
TI  - Comparison of the therapeutic outcomes between surgical resection and
      percutaneous ablation for small hepatocellular carcinoma.
AB  - There seems to be a consensus in regard to the initial treatment of small
      hepatocellular carcinomas (HCCs): either percutaneous ablation or liver resection
      should be selected. Liver resection provides for excellent local control, which
      is one of the most important factors to be considered in the treatment of HCC.
      However, percutaneous ablation has the advantage of less invasiveness, which
      allows for repeated sessions of ablation. However, there has been a longstanding
      debate on which of the two therapeutic modalities might be superior in individual
      cases with various tumor-related and liver function factors. Although it is
      practically difficult to conduct randomized controlled trials (RCTs) to compare
      these two therapeutic modalities, there have been four RCTs published in English,
      which we focus on in this review article. We discuss the aforementioned unsolved
      problem according to the results of these RCTs, in addition to the results of a
      large-scale cohort study and the recommendations of clinical practice guidelines.

PMID- 24566866
TI  - Diagnostic performance of cerebrospinal fluid total tau and phosphorylated tau in
      Creutzfeldt-Jakob disease: results from the Swedish Mortality Registry.
AB  - IMPORTANCE: Identifying a clinical distinction between the invariably lethal
      prion disease Creutzfeldt-Jakob disease (CJD) and nonprion rapidly progressive
      dementias is important and sometimes difficult; thus, reliable tools for
      diagnosis are in great demand. OBJECTIVE: To test the diagnostic performance of
      dementia cerebrospinal fluid (CSF) biomarkers total tau (T-tau), phosphorylated
      tau (P-tau), and the T-tau to P-tau ratio for CJD by analyzing the results from a
      large database of routine clinical samples in combination with diagnosis
      information from the Swedish Mortality Registry. DESIGN, SETTING, AND
      PARTICIPANTS: This was a retrospective cohort study. We cross-referenced the
      Swedish Mortality Registry with a data set of CSF measurements of T-tau and P-tau
      performed in routine clinical testing at the Clinical Neurochemistry Laboratory
      of the Sahlgrenska University Hospital, which serves most of Sweden. The data set
      consisted of 9765 deceased individuals with CSF measures, including 93 with CJD,
      with 52 autopsy-verified samples (56%). MAIN OUTCOMES AND MEASURES: For each
      patient, T-tau and P-tau levels in CSF were measured and the T-tau to P-tau ratio
      was calculated. Biomarker levels (adjusted for age and sex) were analyzed in
      relation to the recorded cause of death and time of death. We specifically tested
      a previously defined CJD biomarker profile (T-tau >1400 ng/L and T-tau to P-tau
      ratio >25). RESULTS: Patients who died of CJD had elevated CSF T-tau levels and T
      tau to P-tau ratio, but not elevated CSF P-tau levels, compared with patients who
      died of Alzheimer disease (AD) and other dementias. The previously defined
      biomarker profile had a specificity of 99.0%, a sensitivity of 78.5%, and a
      positive likelihood ratio of 79.9. When tested against common differential
      diagnoses, the sensitivity, specificity, and positive likelihood ratio of this
      profile was 78.5%, 99.6%, and 196.6, respectively, in relation to AD and 78.5%,
      99.3%, and 109.3, respectively, in relation to other dementias. In CJD
      individuals (n = 30) with repeated measurements, but not in those with AD (n =
      242) or other dementias (n = 258), T-tau levels and T-tau to P-tau ratios
      increased over time. CONCLUSIONS AND RELEVANCE: In this routine clinical setting,
      the combination of increased T-tau levels and increased T-tau to P-tau ratios in
      CJD patients has a very high specificity against important differential diagnoses
      to CJD and may serve as a clinically useful diagnostic test.

PMID- 24566867
TI  - Context-selective death of acute myeloid leukemia cells triggered by the novel
      hybrid retinoid-HDAC inhibitor MC2392.
AB  - HDAC inhibitors (HDACi) are widely used in the clinic to sensitize tumorigenic
      cells for treatment with other anticancer compounds. The major drawback of HDACi
      is the broad inhibition of the plethora of HDAC-containing complexes. In acute
      promyelocytic leukemia (APL), repression by the PML-RARalpha oncofusion protein
      is mediated by an HDAC-containing complex that can be dissociated by
      pharmacologic doses of all trans retinoic acid (ATRA) inducing differentiation
      and cell death at the expense of side effects and recurrence. We hypothesized
      that the context-specific close physical proximity of a retinoid and HDACi
      binding protein in the repressive PML-RARalpha-HDAC complex may permit selective
      targeting by a hybrid molecule of ATRA with a 2-aminoanilide tail of the HDAC
      inhibitor MS-275, yielding MC2392. We show that MC2392 elicits weak ATRA and
      essentially no HDACi activity in vitro or in vivo. Genome-wide epigenetic
      analyses revealed that in NB4 cells expressing PML-RARalpha, MC2392 induces
      changes in H3 acetylation at a small subset of PML-RARalpha-binding sites. RNA
      seq reveals that MC2392 alters expression of a number of stress-responsive and
      apoptotic genes. Concordantly, MC2392 induced rapid and massive, caspase-8
      dependent cell death accompanied by RIP1 induction and ROS production. Solid and
      leukemic tumors are not affected by MC2392, but expression of PML-RARalpha
      conveys efficient MC2392-induced cell death. Our data suggest a model in which
      MC2392 binds to the RARalpha moiety and selectively inhibits the HDACs resident
      in the repressive complex responsible for the transcriptional impairment in APLs.
      Our findings provide proof-of-principle of the concept of a context-dependent
      targeted therapy.

PMID- 24566869
TI  - An interatomic potential for saturated hydrocarbons based on the modified
      embedded-atom method.
AB  - In this work, we developed an interatomic potential for saturated hydrocarbons
      using the modified embedded-atom method (MEAM), a reactive semi-empirical many
      body potential based on density functional theory and pair potentials. We
      parameterized the potential by fitting to a large experimental and first
      principles (FP) database consisting of (1) bond distances, bond angles, and
      atomization energies at 0 K of a homologous series of alkanes and their select
      isomers from methane to n-octane, (2) the potential energy curves of H2, CH, and
      C2 diatomics, (3) the potential energy curves of hydrogen, methane, ethane, and
      propane dimers, i.e., (H2)2, (CH4)2, (C2H6)2, and (C3H8)2, respectively, and (4)
      pressure-volume-temperature (PVT) data of a dense high-pressure methane system
      with the density of 0.5534 g cc(-1). We compared the atomization energies and
      geometries of a range of linear alkanes, cycloalkanes, and free radicals
      calculated from the MEAM potential to those calculated by other commonly used
      reactive potentials for hydrocarbons, i.e., second-generation reactive empirical
      bond order (REBO) and reactive force field (ReaxFF). MEAM reproduced the
      experimental and/or FP data with accuracy comparable to or better than REBO or
      ReaxFF. The experimental PVT data for a relatively large series of methane,
      ethane, propane, and butane systems with different densities were predicted
      reasonably well by the MEAM potential. Although the MEAM formalism has been
      applied to atomic systems with predominantly metallic bonding in the past, the
      current work demonstrates the promising extension of the MEAM potential to
      covalently bonded molecular systems, specifically saturated hydrocarbons and
      saturated hydrocarbon-based polymers. The MEAM potential has already been
      parameterized for a large number of metallic unary, binary, ternary, carbide,
      nitride, and hydride systems, and extending it to saturated hydrocarbons provides
      a reliable and transferable potential for atomistic/molecular studies of complex
      material phenomena involving hydrocarbon-metal or polymer-metal interfaces,
      polymer-metal nanocomposites, fracture and failure in hydrocarbon-based polymers,
      etc. The latter is especially true since MEAM is a reactive potential that allows
      for dynamic bond formation and bond breaking during simulation. Our results show
      that MEAM predicts the energetics of two major chemical reactions for saturated
      hydrocarbons, i.e., breaking a C-C and a C-H bond, reasonably well. However, the
      current parameterization does not accurately reproduce the energetics and
      structures of unsaturated hydrocarbons and, therefore, should not be applied to
      such systems. 

PMID- 24566868
TI  - RSF1 is a positive regulator of NF-kappaB-induced gene expression required for
      ovarian cancer chemoresistance.
AB  - Overexpression or amplification of the RSF1 gene has been associated with poor
      prognosis in various human cancers, including ovarian cancer. In previous work,
      RSF1 was identified as an amplified gene that facilitated the development of
      paclitaxel-resistant ovarian cancer. In the present study, we further
      demonstrated that RSF1 expression inversely correlated with paclitaxel response
      in patients with ovarian cancer and the mouse xenograft model. In addition, RSF1
      overexpressing paclitaxel-resistant ovarian cancer cell lines were found to
      express elevated levels of genes regulated by NF-kappaB, including some involved
      with the evasion of apoptosis (CFLAR, XIAP, BCL2, and BCL2L1) and inflammation
      (PTGS2). In addition, ectopic expression of RSF1 using Tet-off inducible SKOV3
      cells significantly enhanced NF-kappaB-dependent gene expression and
      transcriptional activation of NF-kappaB. An RSF1 knockdown using short hairpin
      RNAs suppressed these same pathways. Moreover, pretreatment with NF-kappaB
      inhibitors or downregulation of NF-kappaB-regulated gene expression considerably
      enhanced paclitaxel sensitivity in RSF1-overexpressing OVCAR3 and/or RSF1-induced
      SKOV3 cells. A coimmunoprecipitation assay revealed that RSF1 interacts with NF
      kappaB and CREB-binding protein, a ubiquitous coactivator for NF-kappaB.
      Recruitment of RSF1 to the NF-kappaB binding element in the PTGS2 and XIAP
      promoters was demonstrated by the chromatin immunoprecipitation assay.
      Furthermore, hSNF2H, a well-known binding partner of RSF1, was partially involved
      in the interaction between RSF1 and NF-kappaB. Taken together, these data suggest
      that RSF1 may function as a coactivator for NF-kappaB, consequently augmenting
      expression of genes necessary for the development of chemoresistance in ovarian
      cancer cells.

PMID- 24566870
TI  - Prevention and treatment of oral mucositis in patients with head and neck cancer
      treated with (chemo) radiation: report of an Italian survey.
AB  - PURPOSE: There is a limited number of therapies with a high level of
      recommendations for mucositis, while several strategies are currently employed
      with a limited evidence for efficacy. A national survey among Italian oncologists
      who treat head and neck cancer (HNC) was conducted in order to assess the most
      common preventive and therapeutic protocols (including nutritional support and
      pain control) for oral mucositis (OM) in patients undergoing chemoradiotherapy.
      METHODS: From September to November 2012, a nationwide electronic survey with 21
      focused items was proposed to chemotherapy and radiotherapy centers. RESULTS: We
      collected 111 answers. Common Terminology Criteria for Adverse Events (CTCAE)
      scale is employed by 55% of the physicians in assessing mucosal toxicity. The
      most relevant predictive factors for OM development are considered smoke, alcohol
      use, planned radiotherapy, and concurrent use of radiosensitizing chemotherapy.
      Prophylactic gastrostomy is adopted in <10% of the patients. Preventive
      antibiotics or antimycotics are prescribed by 46% of the responders (mainly local
      or systemic antimycotic drugs). Alkalinizing mouthwashes or coating agents are
      frequently adopted (70% of the cases). Among therapeutic interventions, systemic
      fluconazole is administered by 80% of the physicians. Pain is mainly treated by
      weak followed by strong opioids. CONCLUSIONS: A variety of preventive and
      therapeutic protocols for OM exists among the participating Italian centers, with
      some uniformity in respect to nutritional support, use of antimycotic and
      painkillers. There is an urgent need for well-conducted clinical trials aimed at
      assessing the best choices for OM prevention and treatment in HNC.

PMID- 24566871
TI  - Mineral dust and NOx promote the conversion of SO2 to sulfate in heavy pollution
      days.
AB  - Haze in China has been increasing in frequency of occurrence as well as the area
      of the affected region. Here, we report on a new mechanism of haze formation, in
      which coexistence with NOx can reduce the environmental capacity for SO2, leading
      to rapid conversion of SO2 to sulfate because NO2 and SO2 have a synergistic
      effect when they react on the surface of mineral dust. Monitoring data from five
      severe haze episodes in January of 2013 in the Beijing-Tianjin-Hebei regions
      agreed very well with the laboratory simulation. The combined air pollution of
      motor vehicle exhaust and coal-fired flue gases greatly reduced the atmospheric
      environmental capacity for SO2, and the formation of sulfate was found to be a
      main reason for the growth of fine particles, which led to the occurrence of
      haze. These results indicate that the impact of motor vehicle exhaust on the
      atmospheric environment might be underestimated. 

PMID- 24566872
TI  - ISS groups: are we speaking the same language?
AB  - BACKGROUND: Despite ISS being a widely accepted tool for measuring injury
      severity, many researchers and practitioners use different partition of ISS into
      severity groups. The lack of uniformity in ISS use inhibits proper comparisons
      between different studies. Creation of ISS group boundaries based on single AIS
      value squares and their sums was proposed in 1988 during Major Trauma Study
      (MTOS) in the USA, but was not validated by analysis of large databases. METHODS:
      A validation study analysing 316,944 patients in the Israeli National Trauma
      registry (INTR) and 249,150 patients in the American National Trauma Data Bases
      (NTDB). A binary algorithm (Classification and Regression Trees (CART)) was used
      to detect the most significantly different ISS groups and was also applied to
      original MTOS data. RESULTS: The division of ISS into groups by the CART
      algorithm was identical in both Trauma Registries and very similar to original
      division in the MTOS. For most samples, the recommended groups are 1-8, 9-14, 16
      24 and 25-75, while in very large samples or in studies specifically targeting
      critical patients there is a possibility to divide the last group into 25-48 and
      50-75 groups, with an option for further division into 50-66 and 75 groups.
      CONCLUSIONS: Using a statistical analysis of two very large databases of trauma
      patients, we have found that partitioning of ISS into groups based on their
      association with patient mortality enables us to establish clear cut-off points
      for these groups. We propose that the suggested partition of ISS into severity
      groups would be adopted as a standard in order to have a common language when
      discussing injury severity.

PMID- 24566873
TI  - Modulation of LPS-stimulated pulmonary inflammation by Borneol in murine acute
      lung injury model.
AB  - The object of our study is to investigate the protective effects of Borneol on
      lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. To determine
      the effects of Borneol on the histopathological changes in mice with ALI,
      inflammatory cell count in bronchoalveolar lavage fluid (BALF) and lung wet/dry
      weight ratio were measured in LPS-challenged mice, and lung histopathologic
      changes observed via paraffin section were assessed. Next, cytokine production
      induced by LPS in BALF and RAW 264.7 cells was measured by enzyme-linked
      imunosorbent assay (ELISA). To further study the mechanism of Borneol-protective
      effects on ALI, nuclear factor-kappaB (NF-kappaB) and mitogen-activated protein
      kinases (MAPKs) pathways were investigated. In the present study, Borneol
      obviously alleviated pulmonary inflammation by reducing inflammatory
      infiltration, histopathological changes, descended cytokine production, and
      pulmonary edema initiated by LPS. Furthermore, Borneol significantly suppressed
      phosphorylation of NF-kappaB/P65, IkappaBa, p38, JNK, and ERK. Taken together,
      our results suggest that Borneol suppressed inflammatory responses in LPS-induced
      acute lung injury through inhibition of the NF-kappaB and MAPKs signaling
      pathways. Borneol may be a promising potential preventive agent for acute lung
      injury treatment. 

PMID- 24566875
TI  - [Phonation onset and simultaneous activation of non-larynx related muscles].
AB  - BACKGROUND: Various voice therapy techniques include not only phonation exercises
      but also measure to regulate tonus of non-larynx related muscles. This is based
      on the belief that the use of non-laryngeal muscles may affect laryngeal muscle
      action during phonation onset und phonation. Here we raised the question if
      indeed a well defined activation of muscles distant to the larynx may effect
      phonation onset time and the vibratory cycles following thereafter. METHOD:
      Prospective partly randomized single center pilot study with 8 healthy
      volunteers. Analysed variables were time of phonation onset and closed quotient
      (Qx) derived via electroglottgraphy. According to a randomization protocol
      volunteers had to press a training device (  +  condition) or to keep the hand
      quiet ( - condition). RESULTS: Comparism of both conditions did not reveal any
      significant difference, however Qx tended to be higher in the  +  condition.
      DISCUSSION: The data presented here does not confirm that activation of hand
      muscles influences phonation onset time. However the preceding vibratory cycles
      may be altered towards a higher tone of intralaryngeal muscles regulating vocal
      fold tension. Further studies including more volunteers or patients with
      functional voice disorders and protocols employing the activation of other muscle
      groups are warranted in order to shed more light into the interrelationship
      between larynx and other muscle activation during phonation.

PMID- 24566876
TI  - Intentional non-adherence to medications by older adults.
AB  - 'The extent to which an individual's medication-taking behaviour and/or execution
      of lifestyle changes, corresponds with agreed recommendations from a healthcare
      provider', is a highly complex behaviour, defined as adherence. However,
      intentional non-adherence is regularly observed and results in negative outcomes
      for patients along with increased healthcare provision costs. Whilst this is a
      consistent issue amongst adults of all ages, the burden of chronic disease is
      greatest amongst older adults. As a result, the absolute prevalence of
      intentional non-adherence is increased in this population. This non-systematic
      review of intentional non-adherence to medication highlights the extent of the
      problem amongst older adults. It notes that age, per se, is not a contributory
      factor in intentionally non-adherent behaviours. Moreover, it describes the
      difference in methodology required to identify such behaviours in contrast to
      reports of non-adherence in general: the use of focus groups, semi-structured,
      one-to-one interviews and questionnaires as opposed to pill counts, electronic
      medication monitors and analysis of prescription refill rates. Using Leventhal's
      Common-Sense Model of Self-Regulation, it emphasizes six key factors that may
      contribute to intentional non-adherence amongst older adults: illness beliefs,
      the perceived risks (e.g. dependence, adverse effects), benefits and necessity of
      potential treatments, the patient-practitioner relationship, inter-current
      physical and mental illnesses, financial constraints and
      pharmaceutical/pharmacological issues (poly-pharmacy/regimen complexity). It
      describes the current evidence for each of these aspects and notes the paucity of
      data validating Leventhal's model in this regard. It also reports on
      interventions that may address these issues and explicitly acknowledges the lack
      of evidence-based interventions available to healthcare practitioners. As a
      result, it highlights five key areas that require urgent research amongst older
      adults: (1) the overlap between intentional and unintentional non-adherence,
      particularly amongst those who may be frail or isolated; (2) the potential
      correlation between symptomatic benefit and intentional vs. unintentional non
      adherence to medication; (3) an evaluation of the source of prescribing (i.e. a
      long-standing provider vs. an acute episode of care) and the patient-prescriber
      relationship as determinants of intentional and unintentional non-adherence; (4)
      the decision-making processes leading to selective intentional non-adherence
      amongst older adults with multiple medical problems; and (5) the development and
      evaluation of interventions designed to reduce intentional non-adherence,
      specifically addressing each of the aspects listed above. 

PMID- 24566874
TI  - Overexpression of Fas and FasL is associated with infectious complications and
      severity of experimental severe acute pancreatitis by promoting apoptosis of
      lymphocytes.
AB  - This study investigated the relationship of Fas and Fas ligand (FasL) expression
      and apoptosis of lymphocytes in relation to the pathogenic immune response and
      infectious complications observed in experimental severe acute pancreatitis in
      mice. Forty male Balb/c mice were randomly divided into control, mild (MAP), and
      severe acute pancreatitis (SAP) groups. Overexpression of Fas/FasL messenger
      ribonucleic acid (mRNA) and protein was observed in spleen-derived lymphocytes in
      SAP (p < 0.01). Apoptosis of these resulted in a depletion of circulating
      lymphocytes in this group (p < 0.05). A further significant change in the SAP
      group with infectious complications was observed. A positive relationship was
      found between the Fas/FasL expression and lymphocyte apoptosis, and negative
      relationships were observed between Fas/FasL expression and CD4(+) and CD19(+)
      lymphocytes and the CD4(+)/CD8(+) ratio in SAP mice (p < 0.01). The results
      suggest that the overexpression of Fas/FasL is associated with infectious
      complications and severity of experimental severe acute pancreatitis by promoting
      apoptosis of lymphocytes. 

PMID- 24566879
TI  - Coeliac disease. Missing villi? The search for coeliac disease in the Asia
      Pacific region.
AB  - Epidemiology studies have shown an ~1% prevalence of coeliac disease in Europe,
      North America, the Middle East and South America, but the prevalence in the Asia
      Pacific region remains relatively unknown. Now, Makharia et al. have proposed
      much needed recommendations to help tackle the problem of coeliac disease in this
      region.

PMID- 24566877
TI  - Reduction of potentially inappropriate medications using the STOPP criteria in
      frail older inpatients: a randomised controlled study.
AB  - BACKGROUND: Hospital admissions may provide an opportunity to discontinue
      potentially inappropriate medications (PIMs) in older patients. Little is known
      about the effect of using the Screening Tool of Older People's potentially
      inappropriate Prescriptions (STOPP) in this context. This study aimed to test the
      hypothesis that specific STOPP recommendations from an inpatient geriatric
      consultation team (IGCT) to the hospital physician leads to reductions in PIMs
      for patients at discharge. METHODS: This was a randomised controlled study in 146
      frail inpatients (in 2011). The intervention consisted of STOPP recommendations
      made by the IGCT to ward physicians to discontinue PIMs, in addition to the
      standard geriatric advice. RESULTS: Intervention (n = 74) and control (n = 72)
      groups were similar in terms of patient characteristics (median age 85 years;
      median number of daily drugs, seven) and PIM distribution (68 and 57 PIMs in 53
      and 51 % of patients, respectively). At discharge, the reduction in PIMs was
      twice as high for the intervention group as for the control group (39.7 and 19.3
      %, respectively; p = 0.013). The proportion of patients who still had one or more
      PIM at discharge did not differ between groups. In the 50 patients followed-up a
      year later, the majority of PIMs that had been stopped during hospitalisation had
      not been restarted after discharge (17/28; 61 %). The clinical relevance of PIMs
      identified at baseline in those patients was considered major (29 %), moderate
      (37 %), minor (5 %), deleterious (8 %), or not assessed (11 %). Discontinuation
      rate was not associated with clinical importance. CONCLUSION: Specific STOPP
      recommendations provided to hospital physicians doubled the reduction of PIMs at
      discharge in frail older inpatients. To further improve the appropriateness of
      prescribing in older patients, clinicians should focus on the STOPP criteria that
      are of major clinical importance, and general practitioners should be actively
      involved.

PMID- 24566878
TI  - Use of benzodiazepines and association with falls in older people admitted to
      hospital: a prospective cohort study.
AB  - BACKGROUND: Hypnosedatives are commonly prescribed for anxiety and sleep
      problems. Changes in pharmacokinetics and pharmacodynamics of benzodiazepines
      (BZDs) during ageing may increase their potential to cause adverse outcomes.
      OBJECTIVE: This study aimed to investigate the use of BZDs in acute care settings
      and explore their association with falls. METHODS: A prospective cohort study was
      undertaken of patients aged over 70 years consecutively admitted to 11 acute care
      hospitals in Australia. Data were collected using the interRAI Acute Care
      assessment tool. Falls were recorded prospectively (in hospital) and
      retrospectively (in the 90 days prior to admission). RESULTS: Of 1,412 patients,
      146 (10.3 %) were taking BZDs at admission and 155 (11.3 %) at discharge.
      Incidence rates of in-hospital fallers for users and non-users of BZDs were not
      statistically different [incidence rate ratio 1.03, 95 % confidence interval (CI)
      0.58-1.82]. There was also no significant association between benzodiazepine use
      at admission and history of falls in the previous 90 days compared with non
      users. However, patients on diazepam were significantly more likely to have a
      history of falls than all other benzodiazepine users (70.8 vs. 36.1 %; p =
      0.002), particularly when compared with oxazepam users (70.8 vs. 25.0 %; p <
      0.001). Adjusting for confounders, use of diazepam at admission was positively
      associated with a history of falls compared with all other benzodiazepine users
      (odds ratio 3.0; 95 % CI 1.1-8.5; p = 0.036). CONCLUSIONS: Different BZDs may
      vary in their propensity to predispose to falls, with diazepam having the
      strongest association. The selection of particular BZDs for older patients should
      be carefully evaluated.

PMID- 24566880
TI  - NAFLD. Metabolic make-up of NASH: from fat and sugar to amino acids.
AB  - NAFLD is regarded unquestionably as one of the components of the metabolic
      syndrome. Hence, metabolic perturbations occurring in the fatty liver become a
      systemic metabolic derangement. The phenotypic switching from fatty liver to NASH
      entails a reprogramming of liver metabolism to fit a stressful metabolic
      environment.

PMID- 24566881
TI  - A "SYDE" effect of hierarchical phosphorylation: possible relevance to the cystic
      fibrosis basic defect.
AB  - The motif "SYDE", incorporating the protein kinase CK2 consensus sequence (S-x-x
      E) has been found to be phosphorylated at both its serine and tyrosine residues
      in several proteins. Of special interest is the case of cystic fibrosis
      Transmembrane-conductance Regulator (CFTR), where this motif is close to the
      residue (F508), whose deletion is the by far commonest cause of cystic fibrosis.
      Intriguingly, however, CFTR S511 cannot be phosphorylated by CK2 to any
      appreciable extent. Using a number of peptide substrates encompassing the CFTR
      "SYDE" site we have recently shown that: (1) failure of CK2 to phosphorylate the
      S(511)YDE motif is due to the presence of Y512; (2) CK2 readily phosphorylates
      S511 if Y512 is replaced by a phospho-tyrosine; (3) the Src family protein
      tyrosine kinase Lyn phosphorylates Y512 in a manner that is enhanced by the
      deletion of F508. These data, in conjunction with the recent observation that by
      inhibiting CK2 the degradation of F508delCFTR is reduced, lead us to hypothesize
      that the hierarchical phosphorylation of the motif SYDE by the concerted action
      of protein tyrosine kinases and CK2 is one of the mechanisms that cooperate to
      the premature degradation of F508delCFTR. 

PMID- 24566882
TI  - Impact of cone dystrophy-related mutations in GCAP1 on a kinetic model of
      phototransduction.
AB  - Cone dystrophy-related mutations in guanylate cyclase-activating protein 1
      (GCAP1) are known to cause severe disturbance of their Ca(2+)-sensing properties
      affecting also their regulatory modes. However, crucial biochemical properties of
      mutant GCAP1 forms have not been fully elucidated and regulatory parameters of
      GCAP1 mutants have not been considered within the context of a comprehensive
      description of the phototransduction cascade kinetics. We investigated therefore
      the structure-function relationships of four dystrophy-relevant point mutations
      in GCAP1 harboring the following amino acid substitutions: E89K, D100E, L151F,
      and G159V. All mutations decrease the catalytic efficiency in regulating the
      target guanylate cyclase and decrease the affinity of Ca(2+)-binding in at least
      one, but in most cases two EF-hand Ca(2+)-binding sites. Although the wild type
      and mutants of GCAP1 displayed large differences in Ca(2+)-binding and
      regulation, circular dichroism (CD) spectroscopy revealed that all proteins
      preserved an intact secondary and tertiary structure with a significant
      rearrangement of the aromatic residues upon binding of Ca(2+). To gain insight
      into the dynamic changes of cyclic GMP levels in a photoreceptor cell, we
      incorporated parameters describing the regulation of target guanylate cyclase by
      GCAP1 mutants into a comprehensive kinetic model of phototransduction. Modeling
      led us to conclude that the contribution of GCAP1 to the dynamic synthesis of
      cyclic GMP in rod cells would depend on the expression level of the wild-type
      form. Although the synthesis rate controlled by GCAP1 remains at a constant
      level, in the case of high expression levels of cone-dystrophy GCAP1 mutants it
      would not contribute at all to shaping the cGMP rate, which becomes dynamically
      regulated solely by the other present Ca(2+)-sensor GCAP2. 

PMID- 24566884
TI  - The second eradication: rinderpest.
AB  - The eradication of rinderpest virus was less celebrated than the eradication of
      smallpox virus. However, this is only the second campaign to eradicate a virus
      worldwide which is successful. This gives the opportunity to recall how important
      rinderpest had been these past centuries for farmers and for public health. 

PMID- 24566883
TI  - Objective versus subjective measurements of palatine tonsil size in adult
      patients with obstructive sleep apnea/hypopnea syndrome.
AB  - The objective of this study was to evaluate the relationship between subjective
      and objective tonsil size measurements in adult patients with obstructive sleep
      apnea/hypopnea syndrome (OSAHS) and compare the tonsil size measurements with the
      severity of disease. Fifty-one adult patients (46 males and 5 females) who failed
      continuous positive airway pressure therapy and underwent OSAHS surgery were
      recruited. Physical examinations, subjective tonsil size grading preoperatively,
      and objective tonsil measurements including size (length, width, and height),
      weight and volume immediately after surgery were recorded. The results showed
      significant positive correlations between subjective tonsil size grading and all
      the parameters of the objective tonsil measurements (p < 0.05). When comparing
      the subjective and objective tonsil measurements with the polysomnographic
      parameters, the subjective grading was significantly correlated with snoring
      index (p < 0.05) but showed only borderline correlation with apnea/hypopnea
      index. However, the objective tonsil measurements were significantly correlated
      with both snoring index and apnea/hypopnea index (both p < 0.05). Although the
      subjective tonsil size grading reflected the objective tonsil measurements, the
      objective tonsil measurements were more meaningful in predicting the severity of
      OSAHS.

PMID- 24566885
TI  - [Evoluting form of cancrum oris, about 55 cases collected at the Academic
      Hospital Yalgado Ouedraogo of Ouagadougou].
AB  - The cancrum oris is still an up to date disease in our environment. The death
      rate and the after effects of this disease make all together the main interest of
      this survey. In a retrospective survey carried out from January 2003 to December
      2012, we colligated 55 cases of progressive cancrum oris followed at the
      stomatological and maxillofacial surgery at the Academic Hospital Yalgado
      OUEDRAOGO. On the epidemiological level, we noticed an impact of 5.5 cases per
      year. The average age of our patients was about 7.64 with a sex ratio of 1.03.
      Most of the patients were from an underprivileged family (96.4%). On the clinical
      level, we noticed that most of the patients consulted only after the gangrene had
      fallen (89.1%) and were seriously affected (67.3%) with a bad oral and dental
      hygiene (38.1%). The attacks were mainly jugal (25%) and labial (24.1%). The
      cancrum oris was in most of the cases associated to broncho pneumonitis, malaria
      and to HIV infection (31.37%). For the medical treatment, we focused on
      resuscitation, re nutrition, hydro electrolytic rebalancing and antibiotherapy.
      The surgical treatment was essentially made on the affected areas, controlled
      skinning and most often followed by sequestrectomy. 81.8% of the patients
      recovered completely from the infection, 60% had after effect injuries. We
      recorded a death rate of 14.5%. In order to overcome this disease we need both
      national and international support.

PMID- 24566886
TI  - Shattering the glass ceiling.

PMID- 24566887
TI  - The level of agreement between child self-reports and parent proxy-reports of
      health-related quality of life in boys with Duchenne muscular dystrophy.
AB  - PURPOSE: To investigate the level of agreement between child self-reports and
      parent proxy-reports of the health-related quality of life (HRQoL) in boys with
      Duchenne muscular dystrophy (DMD) using both classical test theory (CTT) and
      Rasch analysis. METHODS: A total of 63 boys with DMD and their parents completed
      the pediatric quality of life inventory version 4.0 child self-report and parent
      proxy-report of HRQoL, respectively. The data were analyzed using both the CTT
      (scale-score level) and Rasch analysis (item-level). RESULTS: The intraclass
      correlation coefficient (ICC, scale-score level) between children and parents
      showed good to moderate agreement, although parents consistently underestimated
      their child HRQoL. In Rasch analysis (item-level), 1 out of 8 items was
      significantly different between children and parents in the physical health
      scale. Also, 3 out of 15 items were significantly different between those two
      groups in the psychosocial health scale. CONCLUSIONS: By applying both scale
      score and item-level analyses, our study seeks to broaden the understanding of
      the discrepancy of the ratings between child self-reports and parent proxy
      reports. The findings could provide further information about the decision-making
      process when selecting therapy and care programs.

PMID- 24566888
TI  - Performance characteristics of broth-only cultures after revision total joint
      arthroplasty.
AB  - BACKGROUND: Surgeons frequently obtain intraoperative cultures at the time of
      revision total joint arthroplasty. The use of broth or liquid medium before
      applying the sample to the agar medium may be associated with contamination and
      false-positive cultures; however, the degree to which this is the case is not
      known. QUESTIONS/PURPOSES: We (1) calculated the performance characteristics of
      broth-only cultures (sensitivity, specificity, positive predictive value, and
      negative predictive value) and (2) characterized the organisms identified in
      broth to determine whether a specific organism showed increased proclivity for
      true-positive periprosthetic joint infection (PJI). METHODS: A single-institution
      retrospective chart review was performed on 257 revision total joint
      arthroplasties from 2009 through 2010. One hundred ninety (74%) had cultures for
      review. All culture results, as well as treatment, if any, were documented and
      patients were followed for a minimum of 1 year for evidence of PJI. Cultures were
      measured as either positive from the broth only or broth negative. The true
      diagnosis of infection was determined by the Musculoskeletal Infection Society
      criteria during the preoperative workup or postoperatively at 1 year for purposes
      of calculating the performance characteristics of the broth-only culture.
      RESULTS: The sensitivity, specificity, positive predictive value, and negative
      predictive value were 19%, 88%, 13%, and 92%, respectively. The most common
      organism identified was coagulase-negative Staphylococcus (16 of 24 cases, 67%).
      Coagulase-negative Staphylococcus was present in all three true-positive cases;
      however, it was also found in 13 of the false-positive cases. CONCLUSIONS: The
      broth-only positive cultures showed poor sensitivity and positive predictive
      value but good specificity and negative predictive value. The good specificity
      indicates that it can help to rule in the presence of PJI; however, the poor
      sensitivity makes broth-only culture an unreliable screening test. We recommend
      that broth-only culture results be carefully scrutinized and decisions on the
      diagnosis and treatment of infection should be based specifically on the
      Musculoskeletal Infection Society criteria. LEVEL OF EVIDENCE: Level IV,
      diagnostic study. See Instructions for Authors for a complete description of
      levels of evidence.

PMID- 24566889
TI  - What risk factors predict usage of gastrocsoleus recession during tibial
      lengthening?
AB  - BACKGROUND: Tibial lengthening is frequently associated with gastrocsoleus
      contracture and some patients are treated surgically. However, the risk factors
      associated with gastrocsoleus contracture severe enough to warrant surgery during
      tibial lengthening and the consistency with which gastrocsoleus recession (GSR)
      results in a plantigrade foot in this setting have not been well defined.
      QUESTIONS/PURPOSES: We compared patients treated with or without GSR during
      tibial lengthening with respect to (1) clinical risk factors triggering GSR use,
      (2) ROM gains and patient-reported outcomes, and (3) complications after GSR.
      METHODS: Between 2002 and 2011, 95 patients underwent tibial lengthenings
      excluding those associated with bone loss; 82 (83%) were available for a minimum
      followup of 1 year. According to our clinical algorithm, we performed GSR when
      patients had equinus contractures of greater than 10 degrees  while lengthening
      or greater than 0 degrees  before or after lengthening. Forty-one patients
      underwent GSR and 41 did not. Univariate analysis was performed to assess
      independent associations between surgical characteristics and likelihood of
      undergoing GSR. A multivariate regression model and receiver operating
      characteristic curves were generated to adjust for confounders and to establish
      risk factors and any threshold for undergoing GSR. Chart review determined ROM,
      patient-reported outcomes, and complications. RESULTS: Amount and percentage of
      lengthening, age, and etiology were risk factors for GSR. Patients with
      lengthening of greater than 42 mm (odds ratio [OR]: 4.13; 95% CI: 1.82, 9.40; p =
      0.001), lengthening of greater than 13% of lengthening (OR: 3.88; 95% CI: 1.66,
      9.11; p = 0.001), and congenital etiology (OR: 1.90; 95% CI: 0.86, 4.15; p =
      0.109) were more likely to undergo GSR. Adjusting for all other variables,
      increased amount lengthened (adjusted OR: 1.05; 95% CI: 1.02, 1.07; p < 0.001)
      and age (adjusted OR: 1.02; 95% CI: 0.99, 1.05; p = 0.131) were associated with
      undergoing GSR. Patients gained 24 degrees  of ankle dorsiflexion after GSR. Self
      reported functional outcomes were similar between patients with or without GSR.
      Complications included stretch injury to the posterior tibial nerve leading to
      temporary and partial loss of plantar sensation in two patients. CONCLUSIONS:
      Dorsiflexion was maintained and/or restored similarly among patients with or
      without GSR when treated under our algorithm. Functional compromise was not seen
      after GSR. Identification of patients at risk will help surgeons indicate
      patients for surgery. Acute dorsiflexion should be avoided to minimize risk of
      injury to the posterior tibial nerve. LEVEL OF EVIDENCE: Level IV, therapeutic
      study. See Instructions for Authors for a complete description of levels of
      evidence.

PMID- 24566890
TI  - High methodologic quality but poor applicability: assessment of the AAOS
      guidelines using the AGREE II instrument.
AB  - BACKGROUND: The American Academy of Orthopaedic Surgeons (AAOS) is a globally
      recognized leader in musculoskeletal and orthopaedic education. Clinical
      guidelines are one important focus of the AAOS' educational efforts. Although
      their recommendations sometimes generate controversy, a critical appraisal of the
      overall quality of these guidelines has not, to our knowledge, been reported.
      QUESTIONS/PURPOSES: We wished to assess the overall quality of the AAOS
      guidelines using the AGREE II (Advancing Guideline Development, Reporting and
      Evaluation in Health Care) instrument. METHODS: All 14 guidelines available on
      the AAOS website as of August 2, 2013 were evaluated. Appraisal was performed by
      three reviewers, independently, using the AGREE II instrument. This is an
      internationally recognized and validated assessment tool for evaluating guideline
      quality. Interrater reliability was calculated and descriptive statistics were
      performed. Strong interrater reliability was shown using a Spearman's Rho test
      (correlation coefficient >= 0.95). RESULTS: The overall results for AGREE II
      domains across all 14 guidelines were: scope and purpose (median score, 95%),
      stakeholder involvement (median score, 83%), rigor of development (median score,
      94%), clarity of presentation (median score, 92%), applicability (median score,
      48%), and editorial independence (median score, 79%). CONCLUSIONS: This study
      showed that the overall quality of the AAOS guidelines is high, however their
      applicability was found to be poor. The value of guidelines that have a high
      quality but that are difficult for clinicians to implement is questionable.
      Numerous suggestions have been proposed to improve applicability including;
      health economist involvement in guideline production, implementation of pilot
      studies and audit to monitor uptake of the guidelines and clinician feedback
      sessions and barrier analysis studies. Future AAOS guidelines should consider and
      implement steps that can improve their applicability.

PMID- 24566891
TI  - Posterior tibial tendon transfer improves function for foot drop after knee
      dislocation.
AB  - BACKGROUND: Knee dislocation may be associated with an injury to the common
      peroneal nerve with a subsequent foot drop. Previous studies have demonstrated
      good functional results after posterior tibial tendon transfer in patients with
      foot drop. No studies, to our knowledge, have focused exclusively on knee
      dislocation as the cause of common peroneal nerve injury leading to foot drop.
      QUESTIONS/PURPOSES: We determined the percentage of patients developing common
      peroneal nerve paresis after knee dislocation, the symptom improvement rate in
      these patients, and patient-reported outcomes (American Orthopaedic Foot and
      Ankle Society [AOFAS] ankle-hindfoot score), ankle dorsiflexion strength, and ROM
      in patients with no symptom improvement treated with posterior tibial tendon
      transfer. METHODS: Two hundred forty-seven patients with knee dislocation,
      defined as an injury to both the ACL and PCL with an additional injury to the
      lateral and/or medial ligaments (Schenck Classification II to IV), were
      registered in a single institution's database between 1996 and 2011. The database
      was queried for the frequency of documented injuries to the common peroneal nerve
      and, among those, the frequency of spontaneous resolution after this injury.
      Patients demonstrating no active dorsiflexion 12 months after injury generally
      were offered posterior tibial tendon transfer. Postoperatively, patients were
      evaluated for AOFAS score, ankle dorsiflexion strength, and ROM. RESULTS: Forty
      three patients (17%) had a common peroneal nerve paresis at admission. At 1-year
      followup, 15 of 43 patients (35%) had experienced symptom improvement. One
      patient experienced spontaneous improvement later than 1 year after injury. One
      patient was lost to followup. A below-knee amputation was performed in one
      patient due to the initial trauma. Seven patients were satisfied with their
      function using a brace or had medical contraindications to surgical treatment,
      while four patients refused the proposed operation with a tendon transfer,
      leaving 14 patients treated with posterior tibial tendon transfer. In the 12
      patients available for evaluation, mean AOFAS score was 91 of 100. Mean (+/- SD)
      dorsiflexion strength was 118 (+/- 55) Nm on the operated side and 284 (+/- 94)
      Nm on the unaffected side (p < 0.001). Mean ROM was 67 degrees  (+/- 15 degrees )
      on the operated side and 93 degrees  (+/- 14 degrees ) on the unaffected side (p
      < 0.001). CONCLUSIONS: Based on these findings, we recommend posterior tibial
      tendon transfer for treatment of foot drop that persists at least 1 year after
      knee dislocation. LEVEL OF EVIDENCE: Level IV, therapeutic study. See
      Instructions for Authors for a complete description of levels of evidence.

PMID- 24566893
TI  - Interfacial charge separation in Cu2O/RuO(x) as a visible light driven CO2
      reduction catalyst.
AB  - We employ transient absorption spectroscopy to record the absorption spectrum of
      photogenerated charge carriers in Cu2O. We have found that CO2 reduction in Cu2O
      is limited by fast electron-hole recombination. The deposition of RuOx
      nanoparticles on Cu2O results in a twofold increased yield of long-lived
      electrons, indicating partially reduced electron-hole recombination losses. This
      observation correlates with an approximately sixfold increase in the yield of CO2
      reduction to CO. 

PMID- 24566892
TI  - Listr1 locus regulates innate immunity against Listeria monocytogenes infection
      in the mouse liver possibly through Cxcl11 polymorphism.
AB  - Inbred stains of mice display differential susceptibility to infection with the
      common foodborne pathogen Listeria monocytogenes (Lm). Previously, Listr1 and
      Listr2, two genetic loci that control differential sensitivity to Lm infection
      between BALB/cByJ and C57BL/6ByJ mice, were identified. To analyze the role of
      Listr1 in innate immune responses, we employed congenic mice (C.B6By-Listr1/Rag2
      (-/-) ) bearing the C57BL/6ByJ-derived Listr1 locus on a BALB/c-Rag2 (-/-)
      background. Consistent with the results of a previous genetic analysis, the
      congenic mice showed increased susceptibility to Lm infection. The bacterial
      burden in the liver between the congenic and control lines was significantly
      different (P < 0.05) from 24 h postinfection with Lm. Analysis of genes within
      the Listr1 locus identified a frameshift mutation in the Cxcl11 gene of the
      C57BL/6 strain that prevents production of the mature chemokine CXCL11. No
      differences in inflammatory cell infiltration or cells expressing CXCR3 and CXCR7
      which are the receptors of CXCL11 occurred because of CXCL11 deficiency in the
      congenic mice spleens. However, these mice lacked a distinct population of
      CD14(+) positive resident mononuclear cells that express intermediate levels of
      CXCR3 and CXCR7 in the liver. There were fewer microabscesses in the liver of
      CXCL11-deficient mice during the early stage of infection, which is consistent
      with their decreased ability to resist Lm. Our results, when taken together, show
      that the Listr1 locus plays an important role in early control of Lm infection in
      the mouse liver and that Cxcl11 is a candidate gene for disease severity within
      this locus. 

PMID- 24566896
TI  - Setting a research agenda for ductal carcinoma in situ that meets the current
      need for change.

PMID- 24566895
TI  - Potential application of in vivo imaging of impaired lymphatic duct to evaluate
      the severity of pressure ulcer in mouse model.
AB  - Ischemia-reperfusion (IR) injury is a cause of pressure ulcer. However, a
      mechanism underlying the IR injury-induced lymphatic vessel damage remains
      unclear. We investigated the alterations of structure and function of lymphatic
      ducts in a mouse cutaneous IR model. And we suggested a new method for evaluating
      the severity of pressure ulcer. Immunohistochemistry showed that lymphatic ducts
      were totally vanished by IR injury, while blood vessels were relatively
      preserved. The production of harmful reactive oxygen species (ROS) was increased
      in injured tissue. In vitro study showed a high vulnerability of lymphatic
      endothelial cells to ROS. Then we evaluated the impaired lymphatic drainage using
      an in vivo imaging system for intradermally injected indocyanine green (ICG). The
      dysfunction of ICG drainage positively correlated with the severity of subsequent
      cutaneous changes. Quantification of the lymphatic duct dysfunction by this
      imaging system could be a useful strategy to estimate the severity of pressure
      ulcer. 

PMID- 24566894
TI  - Tumor cell plasticity: the challenge to catch a moving target.
AB  - Every cancer cell is "different"--within one and the same tumor, between
      different lesions originating from the same tumor, among different patients
      suffering from the same tumor type, and certainly between different tumor types.
      The complexity of tumor development, with its genetic, phenotypic and functional
      heterogeneity and plasticity within tumors and between primary tumors and
      metastases, underlies the unpredictable influences and stimuli of a tumor
      associated inflammatory microenvironment, immune response, mechanical and
      metabolic stress, therapy-induced inflammation or interaction with microbiota.
      The stochastic and context dependent nature of these factors accounts for the
      difficulties to investigate the impact of resulting cell plasticity on tumor
      development, and justifies the challenge to prevent tumor recurrence. The
      emerging concept of cell plasticity and reciprocity (to change the phenotype by
      processing signals from the environment) throws more light on the actual
      complexity of tumor heterogeneity than can be expected solely from a
      unidirectional, classical cancer stem cell (CSC) model. To date, it remains
      widely unclear to what extent cell plasticity impacts tumor development, and it
      is difficult to assess by current methods. As a high tumor plasticity is likely
      to predict a poor outcome for patients, the future therapeutic challenge will be
      the development of personalized treatment strategies to predict and finally
      prevent cell plasticity in patients.

PMID- 24566897
TI  - Less common genotype variants of TP53 polymorphisms are associated with poor
      outcome in adult patients with adrenocortical carcinoma.
AB  - CONTEXT: The Li-Fraumeni tumor syndrome is strongly associated with
      adrenocortical carcinoma (ACC) and is caused by germline mutations in TP53 in 70%
      of cases. Also, TP53 polymorphisms have been shown to influence both cancer risk
      and clinical outcome in several tumor entities. We, therefore, investigated TP53
      polymorphisms in a cohort of adult patients with ACC. OBJECTIVE: Evaluation of
      the role of TP53 polymorphisms in adult patients with ACC. SUBJECTS AND METHODS:
      Peripheral blood for DNA extraction was collected from 72 ACC patients.
      Polymorphism analysis was carried out by amplification and sequencing of exons
      and adjacent intron sections of TP53. Results were correlated with clinical data
      and the distribution of the polymorphisms was compared with published Caucasian
      control groups. RESULTS: Compared with control groups, genotype frequencies of
      analyzed TP53 polymorphisms among ACC patients were significantly different in
      three out of four polymorphisms: IVS2+38G>C (G/G, P=0.0248), IVS3ins16
      (NoIns/NoIns, P<0.0001; NoIns/Ins, P<0.0001), and IVS6+62A>G (G/G, P<0.0001; G/A,
      P<0.0001). Overall, the survival of ACC patients, which harbored at least one of
      the less frequent genotype variants of four analyzed polymorphisms (n=23), was
      significantly inferior (median survival: 81.0 months in patients with the common
      homozygous genotypes vs 20.0 months in patients with the less frequent genotypes,
      HR 2.56, 95% CI 1.66-7.07; P=0.001). These results were confirmed by
      multivariable regression analysis (HR 2.84, 95% CI 1.52-7.17; P=0.037).
      CONCLUSION: Some TP53 polymorphisms seem to influence overall survival in ACC
      patients. This effect was observed for a combination of polymorphic changes
      rather than for single polymorphisms.

PMID- 24566898
TI  - OCT-1 overexpression is associated with poor prognosis in patients with well
      differentiated gastric cancer.
AB  - Octamer transcription factor-1 (OCT-1) is a well-known transcription factor that
      is reportedly overexpressed in intestinal metaplasia and gastric carcinoma in the
      intestine. In this study, we investigated OCT-1 overexpression as a prognostic
      factor for gastric cancer. The association between OCT-1 overexpression (detected
      using immunohistochemistry) and clinicopathological features including survival
      was evaluated. In vitro gain-of-function approaches were utilized to assess the
      function of OCT-1 in malignancy. Analysis of OCT-1 expression in patients with
      gastric cancer with well-differentiated carcinoma as per the World Health
      Organization classification showed that OCT-1 overexpression was correlated with
      advanced tumor invasion (58.8 % of patients with advanced tumor invasion vs. 21.2
      % of patients with early tumor invasion; p<0.01), lymph node metastasis (63.9 %
      of patients with metastasis vs. 24.1 % of those without; p=0.015), and cancer
      recurrence (83.3 % of patients with recurrence vs. 25.4 % of those without;
      p<0.01), as well as a lower survival rate (62.8 vs. 87.9 Mo; p<0.01). However,
      there were no significant differences in the levels of OCT-1 expression in
      gastric cancer patients with other carcinoma types (p>0.05). Furthermore, we
      found that the proliferation rate of OCT-1-overexpressing MKN-45 cells was higher
      than that of the control cells. OCT-1 overexpression may be a marker for poor
      prognosis in patients with well-differentiated gastric adenocarcinoma.

PMID- 24566899
TI  - ARID1A is downregulated in non-small cell lung cancer and regulates cell
      proliferation and apoptosis.
AB  - ARID1A (AT-rich interactive domain 1A) is a key member of the SWI/SNF chromatin
      modeling complex, and the gene has emerged as a tumor suppressor in various human
      cancers. In the present study, we investigated the expression and clinical
      significance of ARID1A in non-small cell lung cancer (NSCLC). We found that
      ARID1A expression was decreased in NSCLC tissues compared with normal bronchial
      epithelium and was significantly correlated with nodal metastasis, tumor, node,
      metastasis (TNM) stage, and poor differentiation. ARID1A expression was lower in
      lung cancer cell lines than normal bronchial epithelial HBE cell line. We also
      explored the involvement of ARID1A in biological behavior of lung cancer cell
      lines. ARID1A depletion by small interfering RNA (siRNA) in H460 and H1299 cell
      lines promoted proliferation, colony formation ability, and inhibited paclitaxel
      induced apoptosis. Furthermore, we identified that ARID1A regulated several cell
      cycle and apoptosis-related targets such as cyclin D1 and Bcl-2. In addition, the
      activity of Akt phosphorylation was also enhanced after ARID1A depletion. In
      conclusion, our data suggested that ARID1A may serve as an important tumor
      suppressor in NSCLC. 

PMID- 24566900
TI  - TRIM31 is downregulated in non-small cell lung cancer and serves as a potential
      tumor suppressor.
AB  - The present study aims to investigate expression pattern and biological roles of
      TRIM31 in human non-small cell lung cancer (NSCLC). We examined TRIM31 expression
      in 116 NSCLC tissues and 20 corresponding normal lung tissues by
      immumohistochemistry. We found TRIM31 downregulation in 47 out of 116 (40.5 %)
      cancer samples, which correlated with tumor status (p=0.0132), advanced p-TNM
      stage (p=0.001), and nodal metastasis (p=0.0382). TRIM31 expression was lower in
      lung cancer cell lines than normal bronchial cell line HBE. Transfection of
      TRIM31 plasmid was performed in H157 and H1299 cells. TRIM31 overexpression
      inhibited cell growth rate and colony formation ability in both cell lines. In
      addition, expression of cell cycle regulator cyclin D1 and cyclin E were
      decreased after TRIM31 transfection. In conclusion, TRIM31 might serve as a tumor
      suppressor in non-small cell lung cancer.

PMID- 24566901
TI  - Minocycline upregulates pro-survival genes and downregulates pro-apoptotic genes
      in experimental glaucoma.
AB  - PURPOSE: Minocycline, a second-generation tetracycline with anti-inflammatory and
      anti-apoptotic properties, was reported to be neuroprotective in experimental
      glaucoma and optic nerve transection as well as in other neurodegenerative
      diseases. The purpose of this study was to investigate the mechanism underlying
      that neuroprotective effect in murine glaucoma. METHODS: Elevated intraocular
      pressure was induced in 159 rats by the translimbal photocoagulation laser model.
      Minocycline 22 mg/kg or saline was injected intraperitoneally starting 3 days
      before the induction of glaucoma, and continued daily until the animals were
      sacrificed. The effect of minocycline on gene expression was evaluated using a
      quantitative polymerase chain reaction (PCR) array for apoptosis. The involvement
      of selected pro-apoptotic, pro-survival, and inflammatory genes was further
      analyzed by quantitative real-time PCR at multiple time points.
      Immunohistochemistry was used to study the effect of minocycline on microglial
      activation and to localize Bcl-2 changes. RESULTS: Minocycline significantly
      increased the anti-apoptotic gene Bcl-2 expression at day 8 and day 14 after the
      induction of glaucoma (p = 0.04 and p = 0.03 respectively), and decreased IL-18
      expression in the retina at day 14 and day 30 (p = 0.04 and p < 0.001
      respectively). PCR arrays suggested that additional genes were affected by
      minocycline, including Tp53bp2, TRAF4, osteoprotegerin, caspase 1 and 4, and
      members of the tumor necrosis factor superfamily. Additionally, minocycline
      decreased the amount of activated microglia in glaucomatous eyes. CONCLUSIONS:
      These results suggest that minocycline upregulates pro-survival genes and
      downregulates apoptotic genes, thus shifting the balance toward the anti
      apoptotic side in experimental glaucoma.

PMID- 24566902
TI  - Prevalence of age-related macular degeneration in a large European cohort:
      results from the population-based Gutenberg Health Study.
AB  - BACKGROUND: The aim of this study was to describe the sex- and age-specific
      prevalence of age-related macular degeneration (AMD) and its correlation with
      urban or rural residence in a large and relatively young European cohort.
      METHODS: We evaluated fundus photographs from participants in the Gutenberg
      Health Study (GHS), a population-based, prospective, observational, single-centre
      study in the Rhineland-Palatine region in midwestern Germany. The participants
      were 35-74 years of age at enrolment. The fundus images were classified as
      described in the Rotterdam Study and were graded independently by two experienced
      ophthalmologists (CK and UBK) based on the presence of hard and soft drusen,
      retinal pigmentary abnormalities, and signs of atrophic or neovascular age
      related macular generation (AMD). RESULTS: Photographs from 4,340 participants
      were available for grading. Small, hard drusen (<63 MUm, stages 0b and 0c) were
      present in 37.4% of participants (95% confidence interval [CI], stage 0b, 31.6%
      [30.3-33.7]; stage 0c, 5.8% [5.1-6.5]). Early AMD (soft drusen, pigmentary
      abnormalities, stages 1-3) was present in 3.8% of individuals in the youngest age
      group (35-44 years) (95% CI, stage 1a, 0.4% [0.3-0.5%]; stage 1b, 3.2% [2.9
      3.5%]; stage 2a, 0.1% [0.1-0.2%]; stage 2b, 0% [0-0.0%]; stage 3, 0.1% [0.1
      0.2%]), whereas late AMD (stages 4a and 4b) did not appear in the youngest age
      group. In all age groups, signs of early AMD were detected in 11.9% of
      individuals (stage 1a, 2.1% [1.7-2.6]; stage 1b, 8.0% [7.2-8.8]; stage 2a, 1.0%
      [0.7-1.3]; stage 2b, 0.5% [0.3-0.7]; stage 3, 0.3% [0.2-0.6]). Late AMD
      (geographic atrophy or neovascular AMD) was found in 0.2% of individuals (stage
      4a, 0.1 % [0.0-0.2]; stage 4b, 0.1% [0.0-0.2]). AMD increased significantly with
      age (odds ratio [OR], 1.09; 95% CI, 1.08-1.10). Sex, iris colour, and residence
      (rural vs. urban) were not associated with different rates of AMD. CONCLUSIONS:
      In this study, the prevalence of AMD increased dramatically with age; however,
      although AMD is usually thought to occur after age 50, signs of early AMD were
      found in 3.8% of individuals in the youngest age group (younger than 45 years).
      This population-based sample is the first to provide substantial epidemiologic
      data from a large German cohort, including data on macular degeneration in
      younger age groups and incidence data after recall.

PMID- 24566903
TI  - The efficacy of autologous serum eye drops for severe dry eye syndrome: a
      randomized double-blind crossover study.
AB  - BACKGROUND: To evaluate the efficacy of autologous serum (AS) eye drops for the
      symptomatic relief of severe dry eye syndrome (DES), as compared to conventional
      preservative-free artificial tears (PFAT). METHODS: This prospective double-blind
      randomized crossover study used the Ocular Surface Disease Index (OSDI), tear
      film break-up time (TBUT), Schirmer's Test, and OXFORD Scale at baseline and
      after each of two 1-month treatment periods to measure the effect of 20 % diluted
      AS eye drops vs. PFAT in 20 consecutive severe DES patients that were refractory
      to conventional treatment. RESULTS: The study included 20 (18 female and two
      male) severe DES patients (40 eyes). Significantly higher TBUT (P < 0.001,
      Wilcoxon signed-rank test) and a greater decrease in OSDI score (55.18 % decrease
      in the AS treatment group vs. 19.50 % decrease in the PFAT treatment group) (P <
      0.001, Student's paired samples t-test) were observed in the AS treatment group
      after 1 month of treatment. There wasn't a significant difference in Schirmer's
      test and OXFORD conjunctival and corneal vital dying grading scores between the
      two treatment groups after 1 month of treatment (P > 0.05 [Mann-Whitney U test]).
      CONCLUSIONS: AS eye drops were more effective than conventional eye drops for
      improving tear film stability and subjective comfort in patients with severe DES.

PMID- 24566904
TI  - Effect of optical panel distance in a photobioreactor for nutrient removal and
      cultivation of microalgae.
AB  - The aim of present investigation is to assess the effect of illumination area and
      distance of an optical panel (OP) on the growth of microalgae with simultaneous
      removal of nutrients. Four different distances of OPs were used i.e. 225 mm OP
      (Run 1), 150 mm OP (Run 2), 112.5 mm OP (Run 3) and 90 mm distance OP (Run 4) in
      the photobioreactor (PBR) operations. The PBR was equipped with an OP and
      operated with a total volume of 37-l. A batch culture was prepared using an
      initial cell concentration of 1.12 +/- 0.05 g l(-1). The experiments were
      conducted at neutral pH (7.2 +/- 0.3) under dark and light cycles of 8 and 16 h,
      respectively. The diffuse light intensity was recorded as 91, 93, 95 and 98% for
      Run 1, Run 2, Run 3 and Run 4, respectively, at a 300 mm depth level in the PBR.
      The chlorophyll content per cell was found to be an average of 701, 721, 785 and
      808 fg for Run 1, Run 2, Run 3 and Run 4, respectively. High chlorophyll content
      per cell and diffuse light intensity was observed for Run 4 compared to other
      fractions. However, Run 3 sample possessed approximately 10.51% higher biomass
      growth along with 15.22% chemical oxygen demand, 18.15% total nitrogen 2.37% NH4
      N, 15.1% total phosphorus and 15.05% PO4-P more removal than the Run 1. These
      findings suggest that in terms of economic consideration and efficiency of
      nutrients removal, Run 3 is found to be more effective than other samples.
      Moreover, an enhanced growth of Chlorella vulgaris could further be utilized as a
      potential biodiesel source.

PMID- 24566905
TI  - Immune tolerance: mind the gap.

PMID- 24566906
TI  - Tumour immunology: turning macrophages on, off and on again.

PMID- 24566908
TI  - Mucosal immunology: fungal monopoly promotes allergy.

PMID- 24566914
TI  - Intestinal epithelial cells: regulators of barrier function and immune
      homeostasis.
AB  - The abundance of innate and adaptive immune cells that reside together with
      trillions of beneficial commensal microorganisms in the mammalian
      gastrointestinal tract requires barrier and regulatory mechanisms that conserve
      host-microbial interactions and tissue homeostasis. This homeostasis depends on
      the diverse functions of intestinal epithelial cells (IECs), which include the
      physical segregation of commensal bacteria and the integration of microbial
      signals. Hence, IECs are crucial mediators of intestinal homeostasis that enable
      the establishment of an immunological environment permissive to colonization by
      commensal bacteria. In this Review, we provide a comprehensive overview of how
      IECs maintain host-commensal microbial relationships and immune cell homeostasis
      in the intestine. 

PMID- 24566918
TI  - [Standard pO2 for differentiation of primary and secondary hypoxemia].

PMID- 24566915
TI  - Liver fibrosis and repair: immune regulation of wound healing in a solid organ.
AB  - Fibrosis is a highly conserved and co-ordinated protective response to tissue
      injury. The interaction of multiple pathways, molecules and systems determines
      whether fibrosis is self-limiting and homeostatic, or whether it is uncontrolled
      and excessive. Immune cells have been identified as key players in this fibrotic
      cascade, with the capacity to exert either injury-inducing or repair-promoting
      effects. A multi-organ approach was recently suggested to identify the core and
      regulatory pathways in fibrosis, with the aim of integrating the wealth of
      information emerging from basic fibrosis research. In this Review, we focus on
      recent advances in liver fibrosis research as a paradigm for wound healing in
      solid organs and the role of the immune system in regulating and balancing this
      response. 

PMID- 24566919
TI  - [Psychotropic agents in emergency medicine].
AB  - The aim of these two CME articles Psychotropic agents in emergency medicine and
      Psychopharmacotherapy in emergency medicine is to give an overview of drugs and
      their indications in the context of emergency psychiatry. Most relevant for
      prehospital care are benzodiazepines and antipsychotics, like lorazepam,
      diazepam, and haloperidol. But even newer antipsychotics could be suitable for
      emergency medicine. The efficacy of some of the newer antipsychotics, so-called
      atypical antipsychotics, has been studied in emergency psychiatric departments.
      The evidence whether these drugs provide the required efficacy, universality and
      safety profile in emergency medicine, in comparison to, for example, haloperidol,
      is presented in the following article. 

PMID- 24566920
TI  - A freshwater bacterial strain, Shewanella sp. Lzh-2, isolated from Lake Taihu and
      its two algicidal active substances, hexahydropyrrolo[1,2-a]pyrazine-1,4-dione
      and 2, 3-indolinedione.
AB  - Cyanobacterial blooms have become a serious problem in Lake Taihu during the last
      20 years, and Microcystis aeruginosa and Synechococcus sp. are the two dominant
      species in cyanobacterial blooms of Lake Taihu. A freshwater bacterial strain,
      Shewanella sp. Lzh-2, with strong algicidal properties against harmful
      cyanobacteria was isolated from Lake Taihu. Two substances with algicidal
      activity secreted extracellularly by Shewanella sp. Lzh-2, S-2A and S-2B, were
      purified from the bacterial culture of strain Lzh-2 using ethyl acetate
      extraction, column chromatography, and high performance liquid chromatography
      (HPLC) in turn. The substances S-2A and S-2B were identified as
      hexahydropyrrolo[1,2-a]pyrazine-1,4-dione and 2, 3-indolinedione (isatin),
      respectively, based on liquid chromatography-mass spectrometry (LC-MS), gas
      chromatography-mass spectrometry (GC-MS), and hydrogen-nuclear magnetic resonance
      (H-NMR) analyses, making this the first report of their algicidal activity toward
      cyanobacteria. S-2A (hexahydropyrrolo[1,2-a]pyrazine-1,4-dione) had no algicidal
      effects against Synechococcus sp. BN60, but had a high level of algicidal
      activity against M. aeruginosa 9110. The LD50 value of S-2A against M. aeruginosa
      9110 was 5.7 MUg/ml. S-2B (2, 3-indolinedione) showed a potent algicidal effect
      against both M. aeruginosa 9110 and Synechococcus sp. BN60, and the LD50 value of
      S-2B against M. aeruginosa 9110 and Synechococcus sp. BN60 was 12.5 and 34.2
      MUg/ml, respectively. Obvious morphological changes in M. aeruginosa 9110 and
      Synechococcus sp. BN60 were observed after they were exposed to S-2A (or S-2B)
      for 24 h. Approximately, the algicidal activity, the concentration of S-2A and S
      2B, and the cell density of Lzh-2 were positively related to each other during
      the cocultivation process. Overall, these findings increase our knowledge about
      algicidal substances secreted by algicidal bacteria and indicate that strain Lzh
      2 and its two algicidal substances have the potential for use as a bio-agent in
      controlling cyanobacterial blooms in Lake Taihu.

PMID- 24566921
TI  - Unusual site-specific DNA integration into the highly active pseudo-attB of the
      Streptomyces albus J1074 genome.
AB  - The phiC31-encoded recombination system has become a widely used tool for genetic
      analysis of streptomycetes, gene therapy and generation of transgenic animals.
      However, the application of this system, even in the context of its natural host
      genus, Streptomyces, may require a specific approach for each species. In this
      study, we have identified a novel pseudo-attB site, called pseB4, for integration
      of vectors using the phiC31 system. More than 90 % of clones contained two copies
      of pSET152- or pOJ436-based cosmids, after their introduction into S. albus. The
      efficiency of the integration of phiC31-based vectors into pseB4 is therefore
      comparable to that of the integration into attB. Moreover, in contrast with
      integration into the native attB, integration into pseB4 is not polar and does
      not require a complementary sequence in the TT-core region. Furthermore, an
      analysis of conjugation frequency revealed mutual inhibition of plasmid
      integration into either site when both the attB and pseB4 sites were present in
      the genome. 

PMID- 24566916
TI  - Regulation of immune responses by extracellular vesicles.
AB  - Extracellular vesicles, including exosomes, are small membrane vesicles derived
      from multivesicular bodies or from the plasma membrane. Most, if not all, cell
      types release extracellular vesicles, which then enter the bodily fluids. These
      vesicles contain a subset of proteins, lipids and nucleic acids that are derived
      from the parent cell. It is thought that extracellular vesicles have important
      roles in intercellular communication, both locally and systemically, as they
      transfer their contents, including proteins, lipids and RNAs, between cells.
      Extracellular vesicles are involved in numerous physiological processes, and
      vesicles from both non-immune and immune cells have important roles in immune
      regulation. Moreover, extracellular vesicle-based therapeutics are being
      developed and clinically tested for the treatment of inflammatory diseases,
      autoimmune disorders and cancer. Given the tremendous therapeutic potential of
      extracellular vesicles, this Review focuses on their role in modulating immune
      responses, as well as their potential therapeutic applications. 

PMID- 24566922
TI  - Representation of women as authors, reviewers, editors in chief, and editorial
      board members at 6 general medical journals in 2010 and 2011.

PMID- 24566924
TI  - Critically ill patients with influenza A(H1N1)pdm09 virus infection in 2014.

PMID- 24566925
TI  - Influence of different processing treatments on the detectability of nucleic acid
      and protein targets in transgenic soybean meal.
AB  - Influences of dry heating, wet heating, and extrusion on the degradation of DNA
      and protein from transgenic soybean meal (TSM) were analyzed using qualitative
      PCR, quantitative real-time PCR (qPCR), indirect enzyme-linked immunosorbent
      assay (iELISA), and Western blot. The 414-bp Lectin gene was thoroughly degraded
      after dry heating between 75 and 90  degrees C for 30 min, wet heating, and
      extrusion at 165  degrees C with 39 % moisture content. The 483-bp CP4-EPSPS gene
      was not detected after dry heating, wet heating, and extrusion at 120  degrees C
      with 39 % moisture content. The degradation ratios of both Lectin and CP4-EPSPS
      genes increased from 0.4 to 92.1 % and 6.1 to 84.0 % as temperatures rose from 90
      to 165  degrees C. iELISA results of the extruded TSM showed that the CP4-EPSPS
      protein content was reduced from 4.19 to 0.54 % as temperatures rose from 90 to
      150  degrees C and was not detectable at 165  degrees C. Western blot results
      also showed the degradation of CP4-CPSPS protein after extrusion. Our results
      showed that temperature played an essential role in DNA and protein degradation,
      and the content of genetically modified organism (GMO) products may be changed
      after processing and could not reflect the initial content of the products. 

PMID- 24566926
TI  - Biological real-time reaction calorimeter studies for the production of
      penicillin G acylase from Bacillus badius.
AB  - Penicillin G acylase (PGA) is a commercially important enzyme that cleaves
      penicillin G to 6-amino penicillanic acid (6-APA) and phenyl acetic acid (PAA).
      The strain Bacillus badius has been identified as potential producer of PGA. A
      detailed calorimetric investigation on PGA production was carried out to enable
      generation of thermokinetic data possible for commercial application. Reaction
      calorimetric studies coupled with respirometric studies suggested that enzyme
      activity of the species B. badius was calorimetrically traceable. Three phases of
      growth were distinctly noticeable in the metabolic heat-time curve. Increase in
      enzymatic activity with restricted growth confirmed intracellular nature of the
      production process. The estimated heat yields due to biomass growth, 10.026 kJ/g,
      substrate consumption 22.761 kJ/g, and oxygen uptake 383 +/- 10 kJ/mol helped to
      understand the energetic of the organism under study. Low oxycalorific
      coefficient confirmed the existence of fermentation-coupled metabolism of B.
      badius.

PMID- 24566927
TI  - Extraction and immobilization of SA-alpha-2,6-Gal receptors on magnetic
      nanoparticles to study receptor stability and interaction with Sambucus nigra
      lectin.
AB  - The interaction between influenza virus hemagglutinins and host cell with
      terminal sialic acid linked receptors, SA-alpha-2,6-Gal for human strains is
      important to obtain insights into this infectious disease. Sambucus nigra lectin
      has high affinity for SA-alpha-2,6-Gal receptors. The goals of this work were: to
      extract the SA-alpha-2,6-Gal receptors from porcine airways; to perform receptors
      immobilization and study their storage stability; and to determine some
      parameters of interaction between the receptor and S. nigra lectin. The receptor
      isolation was monitored by means of bound sialic acid (BSAc) detection. A major
      band of protein at 66.7 kDa was clearly visible in SDS-PAGE assay. Eighty-one
      percent of isolated glycoproteins were immobilized on magnetic nanoparticles. The
      kinetics of BSAc storage stability at 4  degrees C was approximated as the first
      order reaction with kinetic constant and half-life estimated as 0.062 day(-1) and
      11.2 days, respectively. The dissociation constant (K d) calculated from
      Scatchard's plot was 2.47 * 10(-7) M, and the receptor concentration was equal to
      7.92 * 10(-5) M. Procedure for N-SA-alpha-2,6-Gal -receptors extraction based on
      their affinity to S. nigra lectin with magnetic nanoparticles, and their
      immobilization in active form, was not described previously, and may have wide
      application in designing biosensors or virus removal from areas or contaminated
      samples.

PMID- 24566928
TI  - Measurement of ultrasonic attenuation in diabetic neuropathic sciatic nerves for
      diagnostic and therapeutic applications.
AB  - Measurements of ultrasonic attenuation in the sciatic nerves of rats were
      performed to verify the feasibility of ultrasound diagnosis of peripheral
      neuropathy and to avoid damage to the nerves caused by overheating in pain
      management applications. A rat model of diabetic peripheral neuropathy was
      established. The proximal-segment and middle-segment sciatic nerves of control
      and neuropathic rats were dissected for the attenuation measurement. Two
      commercial ultrasound transducers and a self-developed experimental platform were
      used in the measurements. Using H&E staining and transmission electron (TE)
      microscopy, morphological analysis of the control and neuropathic nerves was
      performed to determine the relationship between attenuation and the histology of
      the nerves. The experimental results showed that the attenuation coefficients of
      the control, second-week, fourth-week, and eighth-week neuropathic nerves were 
      6.68 +/- 0.50, -5.61 +/- 0.34, -6.27 +/- 0.40, and -7.10 +/- 0.35 dB/cm at 2.68
      MHz, respectively. The respective values at 7.50 MHz were -14.96 +/- 0.79, -12.65
      +/- 0.28, -13.98 +/- 1.07, and -16.00 +/- 0.54 dB/cm. The changes in the
      attenuation coefficients were significantly different among the second-week,
      fourth-week, and eighth-week DN nerves. Additionally, the ultrasonic attenuation
      coefficient of the rat sciatic nerve was fourfold that of the cat brain and cow
      liver and twofold that of human muscle.

PMID- 24566923
TI  - Risk as an attribute in discrete choice experiments: a systematic review of the
      literature.
AB  - BACKGROUND: Discrete choice experiments (DCEs) are used to elicit preferences of
      current and future patients and healthcare professionals about how they value
      different aspects of healthcare. Risk is an integral part of most healthcare
      decisions. Despite the use of risk attributes in DCEs consistently being
      highlighted as an area for further research, current methods of incorporating
      risk attributes in DCEs have not been reviewed explicitly. OBJECTIVES: This study
      aimed to systematically identify published healthcare DCEs that incorporated a
      risk attribute, summarise and appraise methods used to present and analyse risk
      attributes, and recommend best practice regarding including, analysing and
      transparently reporting the methodology supporting risk attributes in future
      DCEs. DATA SOURCES: The Web of Science, MEDLINE, EMBASE, PsycINFO and Econlit
      databases were searched on 18 April 2013 for DCEs that included a risk attribute
      published since 1995, and on 23 April 2013 to identify studies assessing risk
      communication in the general (non-DCE) health literature. STUDY ELIGIBILITY
      CRITERIA: Healthcare-related DCEs with a risk attribute mentioned or suggested in
      the title/abstract were obtained and retained in the final review if a risk
      attribute meeting our definition was included. STUDY APPRAISAL AND SYNTHESIS
      METHODS: Extracted data were tabulated and critically appraised to summarise the
      quality of reporting, and the format, presentation and interpretation of the risk
      attribute were summarised. RESULTS: This review identified 117 healthcare DCEs
      that incorporated at least one risk attribute. Whilst there was some evidence of
      good practice incorporated into the presentation of risk attributes, little
      evidence was found that developing methods and recommendations from other
      disciplines about effective methods and validation of risk communication were
      systematically applied to DCEs. In general, the reviewed DCE studies did not
      thoroughly report the methodology supporting the explanation of risk in training
      materials, the impact of framing risk, or exploring the validity of risk
      communication. LIMITATIONS: The primary limitation of this review was that the
      methods underlying presentation, format and analysis of risk attributes could
      only be appraised to the extent that they were reported. CONCLUSIONS:
      Improvements in reporting and transparency of risk presentation from conception
      to the analysis of DCEs are needed. To define best practice, further research is
      needed to test how the process of communicating risk affects the way in which
      people value risk attributes in DCEs.

PMID- 24566929
TI  - In reply: is airwayscope more effective than Macintosh laryngoscope?

PMID- 24566930
TI  - Is airwayscope more effective than Macintosh laryngoscope?

PMID- 24566931
TI  - A systems biology approach to identify intelligence quotient score-related
      genomic regions, and pathways relevant to potential therapeutic treatments.
AB  - Although the intelligence quotient (IQ) is the most popular intelligence test in
      the world, little is known about the underlying biological mechanisms that lead
      to the differences in human. To improve our understanding of cognitive processes
      and identify potential biomarkers, we conducted a comprehensive investigation of
      158 IQ-related genes selected from the literature. A genomic distribution
      analysis demonstrated that IQ-related genes were enriched in seven regions of
      chromosome 7 and the X chromosome. In addition, these genes were enriched in
      target lists of seven transcription factors and sixteen microRNAs. Using a
      network-based approach, we further reconstructed an IQ-related pathway from known
      human pathway interaction data. Based on this reconstructed pathway, we
      incorporated enriched drugs and described the importance of dopamine and
      norepinephrine systems in IQ-related biological process. These findings not only
      reveal several testable genes and processes related to IQ scores, but also have
      potential therapeutic implications for IQ-related mental disorders. 

PMID- 24566932
TI  - Na+/H+ exchanger-1 reduces podocyte injury caused by endoplasmic reticulum stress
      via autophagy activation.
AB  - Podocyte injury has a critical role in the pathogenesis of proteinuria. Induction
      of endoplasmic reticulum (ER) stress is thought to lead to podocyte injury;
      however, no effective strategy for reducing ER stress-induced injury has been
      identified. We investigated specific mechanisms for reducing podocyte injury
      caused by ER stress. We found that the induction of ER stress in podocytes was
      related to cytoskeleton injury and increased proteinuria, which was associated
      with autophagy activation and downregulation of Na(+)/H(+) exchanger-1 (NHE-1) in
      the rat model of passive Heymann nephritis. Using mouse podocyte cells (MPCs), we
      showed that ER stress could lead to podocyte injury accompanied by autophagy
      activation, and the disturbance of autophagy aggravated cytoskeleton loss under
      conditions of ER stress. The balance between autophagy activation and ER stress
      was critical to podocyte survival, in which the efficiency of autophagy could
      have a pivotal role. Strikingly, the overexpression and small interfering RNA
      knockdown of NHE-1 results suggested that NHE-1 exerts a protective effect by
      reducing the loss of synaptopodin in MPCs exposed to ER stress. This protective
      mechanism involves NHE-1 activation of autophagy via the PI3K/Akt pathway to
      reduce ER stress injury in podocytes. This mechanism may provide a new pathway to
      prevent podocyte injury. 

PMID- 24566934
TI  - Reality and revisionism: new evidence for Andrew C Ivy's claim to authorship of
      the Nuremberg Code.

PMID- 24566935
TI  - The development of equivalence as a mechanism to improve prison healthcare.

PMID- 24566933
TI  - Metabolically induced liver inflammation leads to NASH and differs from LPS- or
      IL-1beta-induced chronic inflammation.
AB  - The nature of the chronic inflammatory component that drives the development of
      non-alcoholic steatohepatitis (NASH) is unclear and possible inflammatory
      triggers have not been investigated systematically. We examined the effect of non
      metabolic triggers (lipopolysaccharide (LPS), interleukin-1beta (IL-1beta),
      administered by slow-release minipumps) and metabolic dietary triggers
      (carbohydrate, cholesterol) of inflammation on the progression of bland liver
      steatosis (BS) to NASH. Transgenic APOE3*Leiden.huCETP (APOE3L.CETP) mice fed a
      high-fat diet (HFD) developed BS after 10 weeks. Then, inflammatory triggers were
      superimposed or not (control) for six more weeks. Mouse livers were analyzed with
      particular emphasis on hallmarks of inflammation which were defined in human
      liver biopsies with and without NASH. Livers of HFD-treated control mice remained
      steatotic and did not progress to NASH. All four inflammatory triggers activated
      hepatic nuclear factor-kappaB (NF-kappaB) significantly and comparably (>=5
      fold). However, HFD+LPS or HFD+IL-1beta did not induce a NASH-like phenotype and
      caused intrahepatic accumulation of almost exclusively mononuclear cells. By
      contrast, mice treated with metabolic triggers developed NASH, characterized by
      enhanced steatosis, hepatocellular hypertrophy, and formation of mixed-type
      inflammatory foci containing myeloperoxidase-positive granulocytes (neutrophils)
      as well as mononuclear cells, essentially as observed in human NASH. Specific for
      the metabolic inducers was an activation of the proinflammatory transcription
      factor activator protein-1 (AP-1), neutrophil infiltration, and induction of risk
      factors associated with human NASH, that is, dyslipidemia (by cholesterol) and
      insulin resistance (by carbohydrate). In conclusion, HFD feeding followed by NF
      kappaB activation per se (LPS, IL-1beta) does not promote the transition from BS
      to NASH. HFD feeding followed by metabolically evoked inflammation induces
      additional inflammatory components (neutrophils, AP-1 pathway) and causes NASH. 

PMID- 24566936
TI  - NHS Scotland reduces the postcode lottery for hip arthroplasty: an ecological
      study of the impact of waiting time initiatives.
AB  - OBJECTIVES: Following the election of the Labour government in 1997, policies
      were developed in England to reduce waiting times for NHS treatment with
      commitments to reduce health inequalities. Similar policies were adopted in
      Scotland but with less emphasis on the use of the private sector to deliver NHS
      treatments than in England. This study uses routinely collected NHS Scotland data
      to analyse geographical and socioeconomic inequalities in elective hip
      arthroplasty treatment before and after the introduction of the waiting time
      initiatives in Scotland in 2003. DESIGN: Ecological study design. SETTING:
      Scotland. PARTICIPANTS: NHS-funded patients receiving elective hip arthroplasty
      delivered by the NHS and private hospitals between 1 April 1998 and 31 March
      2008. MAIN OUTCOME MEASURES: Directly standardised treatment rates and incidence
      rate ratios calculated using Poisson regression. RESULTS: There was a 42%
      increase in NHS-funded hip arthroplasties carried out in Scotland from 4095 in
      2002-2003 (1 April 2002-31 March 2003) to 5829 in 2007-2008. There is evidence of
      a statistically significant reduction in geographical inequality (likelihood
      ratio test p < 0.001) but no evidence of any statistically significant change in
      socioeconomic inequality (p = 0.108), comparing the 5 years after 1 April 2003
      with the 5 years before 1 April 2003. The number of NHS-funded hip arthroplasties
      undertaken privately rose from 1.1% in 2002-2003 to 2.9% in 2007-2008, whereas
      the NHS Golden Jubilee National Hospital increased its share from 3.3% to 10.6%
      over the same period. CONCLUSIONS: The reduction in geographical inequality, or
      'postcode lottery', in hip arthroplasty treatment in Scotland may be due to
      increased NHS capacity, in particular the development of the NHS Golden Jubilee
      National Hospital in Clydebank, Greater Glasgow as a dedicated centre to reduce
      surgery waiting times.

PMID- 24566937
TI  - Examining the clinical correlates of autism spectrum disorder in youth by
      ascertainment source.
AB  - To examine whether presentation of autism spectrum disorder (ASD) and associated
      patterns of psychiatric comorbidity and dysfunction vary by referral source. ASD
      youth referred to a specialized ambulatory program for ASD (N = 143) were
      compared to ASD youth referred to a general child psychiatry clinic (N = 217).
      More ASD clinic youth met criteria for a more robust form of ASD (autistic
      disorder); more youth referred to the psychiatry clinic met criteria for broader
      spectrum ASD (pervasive developmental disorder not otherwise specified). General
      psychiatry clinic youth with ASD suffered from a greater burden of
      psychopathologies and higher levels of dysfunction. The presentation of ASD in
      psychiatrically referred youth differs between general and ASD-specialized
      clinics, though both referral populations have high levels of comorbidity and
      dysfunction.

PMID- 24566938
TI  - Molecular biomarkers of epileptogenesis.
AB  - Epileptogenesis, a process leading to a reduced threshold for seizures after
      transient brain insults, as well as the mechanisms underlying the propensity to
      generate spontaneous epileptic seizures, are highly dynamic processes. Biomarkers
      -objective measures of biological processes--would be excellent tools for
      monitoring epileptogenesis and the dynamics of increased seizure propensity, as
      well as the potential to interfere, for example pharmacologically, with these key
      pathological aspects of epilepsy. Molecular biomarkers have revolutionized
      therapies, as well as response prediction and monitoring of therapies in other
      biomedical fields. However, high-impact molecular biomarkers are still not
      available in the context of epilepsy. Several factors, such as the large
      heterogeneity of epileptic syndromes and their underlying pathological patterns,
      as well as the limited availability of tissue samples, represent a particular
      challenge to the development of molecular biomarkers in epileptogenesis and
      epilepsy. However, substantial technical progress has been made recently with
      respect to biomarker characterization and monitoring by large throughput analysis
      on the genomic, mRNA, and proteomic levels, starting from minute amounts of brain
      tissue or body fluids, for example cerebrospinal fluid, blood, serum, or plasma.
      Given the substantial cellular- and network-level functional pathophysiology
      involved in epilepsy, it may be beneficial in the future to combine molecular
      analysis with other methods, such as imaging and electrophysiological biomarkers.

PMID- 24566939
TI  - Genetic biomarkers in epilepsy.
AB  - The identification of valid biomarkers for outcome prediction of diseases and
      improvement of drug response, as well as avoidance of side effects is an emerging
      field of interest in medicine. The concept of individualized therapy is becoming
      increasingly important in the treatment of patients with epilepsy, as predictive
      markers for disease prognosis and treatment outcome are still limited. Currently,
      the clinical decision process for selection of an antiepileptic drug (AED) is
      predominately based on the patient's epileptic syndrome and side effect profiles
      of the AEDs, but not on effectiveness data. Although standard dosages of AEDs are
      used, supplemented, in part, by therapeutic monitoring, the response of an
      individual patient to a specific AED is generally unpredictable, and the standard
      care of patients in antiepileptic treatment is more or less based on trial and
      error. Therefore, there is an urgent need for valid predictive biomarkers to
      guide patient-tailored individualized treatment strategies in epilepsy, a
      research area that is still in its infancy. This review focuses on genomic
      factors as part of an individual concept for AED therapy summarizing examples
      that influence the prognosis of the disease and the response to AEDs, including
      side effects. 

PMID- 24566941
TI  - [Placement of a central venous catheter in cases of persistent left superior vena
      cava].
AB  - This article presents a case report on the placement of a central venous catheter
      (CVC) in a patient with an unknown persistent left superior vena cava (PLSVC).
      Normally, PLSVCs remain asymptomatic but can be associated with disastrous
      consequences for the patient during placement of a CVC particularly due to
      vascular perforation and pulmonary injury. A PLSCV is particularly common in
      association with congenital heart defects; however, otherwise healthy patients
      can also be affected. As the presence of a PLSCV is normally unknown special
      attention must be paid in every patient during placement of a CVC. 

PMID- 24566940
TI  - Autoimmune epilepsies.
AB  - In patients with immune-associated disorders of the gray central nervous system
      matter (including recurrent seizures), antibodies against intracellular antigens
      have been discovered since the 1980s/1990s. In recent years, new antibodies
      against surface antigens have also been discovered. In two respects, these
      antibodies are even more interesting than the ones to intracellular antigens as,
      first, they promise a better response to immunotherapy; and, second, these
      antibodies contribute greatly to the understanding of the disease mechanisms.
      Whereas in encephalitides with antibodies against intracellular antigens, a
      cytotoxic T-cell-mediated response seems to be responsible for neuronal cell
      loss, in encephalitides with autoantibodies against surface antigens these
      antibodies are probably the relevant pathogenic agents in the associated disease
      conditions. On the one hand, antibodies to the NR1 subunit of N-methyl-D
      aspartate receptors have been suggested to cause internalization and loss of
      these receptors without any cell destruction. This mechanism can explain the
      reversible functional effects caused by these antibodies. On the other hand,
      antibody- and complement-mediated destructive, and the irreversible effects of
      antibodies against the voltage-gated potassium channel antigens have been noted.
      These emerging findings make it plausible that immunological therapies,
      preferably early after characterization of the antibodies, offer opportunities to
      restore the health of affected patients. 

PMID- 24566942
TI  - Circulating microRNA testing for the early diagnosis and follow-up of colorectal
      cancer patients.
AB  - Early detection of colorectal cancer (CRC) is key for prevention and the ability
      to impact long-term survival of CRC patients. However, the compliance rate of
      recommended colonoscopy for the population aged from 50 to 75 years is only 50-75
      % in the US. A highly sensitive and specific non-invasive test is needed to
      enhance CRC management. As for late-stage patients, a non-invasive prognostic
      biomarker is also critical for improving patient treatment protocols. The
      discovery that non-coding microRNAs (miRNAs) are stable in body fluids such as
      plasma, serum and exosomes presents the opportunity to develop novel strategies,
      taking advantage of circulating miRNAs as early diagnostic biomarkers of CRC. The
      goal of using circulating miRNA-based prognostic biomarkers for CRC patients has
      been pursued extensively. In this review, we will try to cover the major recent
      advancements at the frontier of this research area. 

PMID- 24566943
TI  - Association of Rho-kinase 1 (ROCK1) gene polymorphisms with Behcet's disease.
AB  - BACKGROUND AND OBJECTIVE: Behcet's disease (BD) is a chronic inflammatory
      vasculitis presenting with flares and silent periods usually between 15 and 40
      years of age. The aim of this study was to evaluate the possible association
      between Rho-kinase 1 (ROCK1) gene polymorphisms and patients with BD in a Turkish
      population. METHODS: A total of 192 BD patients and 255 healthy controls of
      similar age and sex were enrolled in this study. Polymorphisms were analyzed in
      genomic DNA using a BioMark HD dynamic array system. RESULTS: In the presence of
      CC genotype for rs73963110, CT genotype for rs111874856 (Val355Ile), and TC
      genotype for rs112130712 (Lys1054Arg) polymorphisms, the risk of BD increased
      12.13-, 15.05-, and 16.28-fold, respectively (p < 0.0001). There was a lower
      frequency of the GA genotype of the rs112108028 (Pro1164Leu) polymorphisms in BD
      (10.3 %) compared with controls (39.7 %; p < 0.0001). Marked associations between
      these polymorphisms and the manifestations of BD were recorded. CONCLUSION: This
      is the first study to show that ROCK1 gene polymorphisms may have a significant
      impact on susceptibility to BD.

PMID- 24566944
TI  - Demineralization after balloon kyphoplasty with calcium phosphate cement: a
      histological evaluation in ten patients.
AB  - PURPOSE: Balloon kyphoplasty (BKP) with calcium phosphate cement (CPC) is
      increasingly being used for spinal surgery in younger patients. In routinely
      performed follow-up CT scans we observed considerable areas of demineralization
      in CPC processed vertebrae in several patients. To rule out infections or
      inflammations histological examinations were planned for these patients. METHODS:
      Ten patients (23-54 years; six men) with significant demineralization areas in CT
      scans after CPC balloon kyphoplasty were selected. Punch biopsies from these
      areas were taken in local anesthesia using a biopsy needle. One half of the
      specimen was decalcified and embedded in paraffin, and sections were examined
      histologically using hematoxylin and eosin, Van Gieson, and trichrome staining.
      The second half of the specimen was cast directly in methyl methacrylate and
      sections were examined by Paragon and von Kossa/Safranin staining. Stained slides
      were viewed under light microscopy. RESULTS: Bone-punch specimens were taken at
      17.5 months (mean) after BKP with CPC. In most cases, the cement was well
      surrounded by newly formed lamellar bone with very tight connections between the
      cement and new bone. Unmineralized areas were observed sporadically at the cement
      surface and adjacent to the implant. There were no pronounced signs of
      inflammation or osteolysis of adjacent bone. No complications were observed
      during or following patients' biopsy procedures. CONCLUSIONS: CPC demonstrated
      good biocompatibility and osseointegration in clinical use, with no evidence of
      inflammation or osteonecrosis. Demineralized areas in CT scans could be a result
      of remodeling of the cancellous bone in vertebral bodies.

PMID- 24566946
TI  - Interventions for preventing the spread of infestation in close contacts of
      people with scabies.
AB  - BACKGROUND: Scabies, caused by Sarcoptes scabiei variety hominis or the human
      itch mite, is a common parasitic infection. While anyone can become infected, it
      causes significant morbidity in immunocompromised hosts and it spreads easily
      between human hosts where there is overcrowding or poor sanitation. The most
      common symptom reported is itch which is worse at night. As the symptoms are
      attributed to an allergic reaction to the mite, symptoms usually develop between
      four to six weeks after primary infection. Therefore, people may be infected for
      some time prior to developing symptoms. During this time, while asymptomatic,
      they may spread infection to others they are in close contact with. Consequently,
      it is usually recommended that when an index case is being treated, others who
      have been in close contact with the index case should also be provided with
      treatment. OBJECTIVES: To assess the effects of prophylactic interventions for
      contacts of people with scabies to prevent infestation in the contacts. SEARCH
      METHODS: We searched electronic databases (Cochrane Occupational Safety and
      Health Review Group Specialised Register, CENTRAL (The Cochrane Library), MEDLINE
      (Ovid), Pubmed, EMBASE, LILACS, CINAHL, OpenGrey and WHO ICTRP) up to November
      2013. SELECTION CRITERIA: Randomised controlled trials (RCTs) or cluster RCTs
      which compared prophylactic interventions which were given to contacts of index
      cases with scabies infestation. Interventions could be compared to each other, or
      to placebo or to no treatment. Both drug treatments and non-drug treatments were
      acceptable. DATA COLLECTION AND ANALYSIS: Two authors intended to extract
      dichotomous data (developed infection or did not develop infection) for the
      effects of interventions and report this as risk ratios with 95% confidence
      intervals. We intended to report any adverse outcomes similarly. MAIN RESULTS: We
      did not include any trials in this review. Out of 29 potentially-relevant
      studies, we excluded 16 RCTs as the data for the contacts were either not
      reported or were reported only in combination with the outcomes for the index
      cases. We excluded a further 11 studies as they were not RCTs. We also excluded
      one study as not all subjects were examined at baseline and follow-up, and
      another as it was a case study. AUTHORS' CONCLUSIONS: The effects of providing
      prophylactic treatments for contacts of people with scabies to prevent
      infestation are unknown. We need well-designed RCTs of the use of prophylactic
      measures to prevent the transmission of scabies conducted with people who had the
      opportunity for prolonged skin contact with an index case, such as family
      members, healthcare workers or residential care personnel, within the previous
      six weeks.

PMID- 24566945
TI  - Which isolated sperm abnormality is most related to sperm DNA damage in men
      presenting for infertility evaluation.
AB  - BACKGROUND: Sperm DNA damage is common in infertile men and is associated with
      poor semen parameters but the impact of an isolated sperm abnormality on sperm
      DNA damage has not been studied. OBJECTIVE: To evaluate sperm DNA damage in a
      large cohort of infertile men with isolated sperm defects. DESIGN, SETTING AND
      PARTICIPANTS: Retrospective study of 1084 consecutive, non-azoospermic infertile
      men with an isolated sperm defect: isolated oligozoospermia (iOligo), isolated
      asthenozoospermia (iAstheno) or isolated teratozoospermia (iTerato). OUTCOME
      MEASUREMENTS AND STATISTICAL ANALYSIS: We examined and compared clinical
      parameters, conventional semen parameters and %sperm DNA fragmentation (%SDF,
      assessed by flow cytometry-based Terminal deoxynucleotidyl transferase-mediated
      dUTP Nick End-Labeling assay) in the three groups of men. RESULTS AND
      LIMITATIONS: The mean (+/-SD) %SDF was significantly higher in the iAstheno
      compared to the iOligo and iTerato groups (25.0 +/- 14.0 vs. 19.2 +/- 11.6 and
      20.7 +/- 12.1 %, respectively, P < 0.0001). Similarly, the proportion of men with
      high %SDF (>30 %) was significantly higher in the iAstheno compared to the iOligo
      and iTerato groups (31 % vs. 18 % and 19 %, respectively, P < 0.0001). In the
      group of 713 men with iAstheno, %SDF was positively correlated with paternal age
      (r = 0.20, P < 0.0001) and inversely correlated with %progressive motility (r = 
      0.18, P < 0.0001). In the subset of 218 men with iTerato, %SDF was also
      positively correlated with paternal age (r = 0.15, P = 0.018) and inversely
      correlated with %progressive motility (r = -0.26, P = 0.0001). CONCLUSIONS: In
      this large cohort of infertile men with isolated sperm abnormalities, we have
      found that the sperm DNA fragmentation level is highest in the men with sperm
      motility defects and that 31 % of these men have high levels of sperm DNA
      fragmentation. The data indicate that poor motility is the sperm parameter
      abnormality most closely related to sperm DNA damage.

PMID- 24566947
TI  - Vegetarian diets and blood pressure: a meta-analysis.
AB  - IMPORTANCE Previous studies have suggested an association between vegetarian
      diets and lower blood pressure (BP), but the relationship is not well
      established. OBJECTIVE To conduct a systematic review and meta-analysis of
      controlled clinical trials and observational studies that have examined the
      association between vegetarian diets and BP. DATA SOURCES MEDLINE and Web of
      Science were searched for articles published in English from 1946 to October 2013
      and from 1900 to November 2013, respectively. STUDY SELECTION All studies met the
      inclusion criteria of the use of (1) participants older than 20 years, (2)
      vegetarian diets as an exposure or intervention, (3) mean difference in BP as an
      outcome, and (4) a controlled trial or observational study design. In addition,
      none met the exclusion criteria of (1) use of twin participants, (2) use of
      multiple interventions, (3) reporting only categorical BP data, or (4) reliance
      on case series or case reports. DATA EXTRACTION AND SYNTHESIS Data collected
      included study design, baseline characteristics of the study population, dietary
      data, and outcomes. The data were pooled using a random-effects model. MAIN
      OUTCOMES AND MEASURES Net differences in systolic and diastolic BP associated
      with the consumption of vegetarian diets were assessed. RESULTS Of the 258
      studies identified, 7 clinical trials and 32 observational studies met the
      inclusion criteria. In the 7 controlled trials (a total of 311 participants; mean
      age, 44.5 years), consumption of vegetarian diets was associated with a reduction
      in mean systolic BP (-4.8 mm Hg; 95% CI, -6.6 to -3.1; P < .001; I2 = 0; P = .45
      for heterogeneity) and diastolic BP (-2.2 mm Hg; 95% CI, -3.5 to -1.0; P < .001;
      I2 = 0; P = .43 for heterogeneity) compared with the consumption of omnivorous
      diets. In the 32 observational studies (a total of 21,604 participants; mean age,
      46.6 years), consumption of vegetarian diets was associated with lower mean
      systolic BP (-6.9 mm Hg; 95% CI, -9.1 to -4.7; P < .001; I2 = 91.4; P < .001 for
      heterogeneity) and diastolic BP (-4.7 mm Hg; 95% CI, -6.3 to -3.1; P < .001; I2 =
      92.6; P < .001 for heterogeneity) compared with the consumption of omnivorous
      diets. CONCLUSIONS AND RELEVANCE Consumption of vegetarian diets is associated
      with lower BP. Such diets could be a useful nonpharmacologic means for reducing
      BP.

PMID- 24566948
TI  - Is the detection rate of 18F-choline PET/CT influenced by androgen-deprivation
      therapy?
AB  - PURPOSE: To evaluate if the detection rate (DR) of (18)F-choline (18F-CH) PET/CT
      is influenced by androgen-deprivation therapy (ADT) in patients with prostate
      cancer (PC) already treated with radical intent and presenting biochemical
      relapse. MATERIALS AND METHODS: We have retrospectively evaluated (18)F-CH PET/CT
      scans of 325 consecutive PC patients enrolled in the period November 2009 to
      December 2012 previously treated with radical intent and referred to our centre
      to perform (18)F-CH PET/CT for biochemical relapse. Two different groups of
      patients were evaluated. group A included the whole sample of 325 patients (mean
      age 70 years, range: 49-86) who presented trigger PSA between 0.1 and 80 ng/ml
      (mean 5.5 ng/ml), and group B included 187 patients (mean age 70 years, range 49
      86) with medium-low levels of trigger PSA ranging between 0.5 and 5 ng/ml (mean
      PSA 2.1 ng/ml); group B was chosen in order to obtain a more homogeneous group of
      patients in terms of PSA values also excluding both very low and very high PSA
      levels avoiding the "a priori" higher probability of negative or positive PET
      scan, respectively. At the time of examination, 139 patients from group A and 72
      patients from group B were under ADT: these patients were considered to be
      hormone-resistant PC patients because from their oncologic history (>18 months)
      an increase of PSA levels emerged despite the ongoing ADT. The relationship
      between (18)F-CH PET/CT findings and possible clinical predictors was
      investigated using both univariate and multivariate binary logistic regression
      analyses, including trigger PSA and ADT. RESULTS: Considering the whole
      population, overall DR of (18)F-CH PET was 58.2 % (189/325 patients). In the
      whole sample of patients (group A), both at the univariate and multivariate
      logistic regression analysis, trigger PSA and ADT were significantly correlated
      with the DR of (18)F-CH PET (p < 0.05). Moreover, the DR in patients under ADT
      (mean PSA 7.8 ng/ml) was higher than in patients not under ADT (mean PSA 3.9
      ng/ml), (DR was 70.5 % and 48.9 %, respectively; p < 0.001), therefore,
      demonstrating the existence of a significant correlation between the DR of (18)F
      CH PET and ADT. In group B patients only trigger PSA resulted a reliable
      predictor of the (18)F-CH positivity, since ADT was not correlated to the DR of
      (18)F-CH PET (p = 0.061). Also in group B the DR of (18)F-CH PET in patients
      under ADT was higher than in patients not under ADT (65.3 % and 51.3 %,
      respectively) but the difference was not significant without a statistically
      significant correlation in the Mann Whitney test (p = 0.456) therefore,
      suggesting the lack of correlation between DR (18)F-CH PET/CT and ADT.
      CONCLUSION: Similarly to previous published studies, in our series the overall DR
      of (18)F-CH PET/CT was 58 % and was significantly correlated to trigger PSA. The
      most important finding of the present study is that ADT does not negatively
      influence DR of (18)F-CH PET/CT in PC patients with biochemical relapse;
      therefore, it can be suggested that it is not necessary to withdraw ADT before
      performing (18)F-CH PET/CT.

PMID- 24566950
TI  - Radiolabelled apoptotic probe may be a vehicle for a novel multimodality
      radionuclide tumour therapy.

PMID- 24566949
TI  - Cross sectional PET study of cerebral adenosine A1 receptors in premanifest and
      manifest Huntington's disease.
AB  - PURPOSE: To study cerebral adenosine receptors (AR) in premanifest and manifest
      stages of Huntington's disease (HD). METHODS: We quantified the cerebral binding
      potential (BP ND) of the A1AR in carriers of the HD CAG trinucleotide repeat
      expansion using the radioligand [(18) F]CPFPX and PET. Four groups were
      investigated: (i) premanifest individuals far (preHD-A; n = 7) or (ii) near
      (preHD-B; n = 6) to the predicted symptom onset, (iii) manifest HD patients (n =
      8), and (iv) controls (n = 36). RESULTS: Cerebral A1AR values of preHD-A subjects
      were generally higher than those of controls (by up to 31%, p < .01, in the
      thalamus on average). Across stages a successive reduction of A1AR BPND was
      observed to the levels of controls in preHD-B and undercutting controls in
      manifest HD by down to 25%, p < .01, in the caudatus and amygdala. There was a
      strong correlation between A1AR BP ND and years to onset. Before onset of HD, the
      assumed annual rates of change of A1AR density were -1.2% in the caudatus, -1.7%
      in the thalamus and -3.4% in the amygdala, while the corresponding volume losses
      amounted to 0.6%, 0.1% and 0.2%, respectively. CONCLUSIONS: Adenosine receptors
      switch from supra to subnormal levels during phenoconversion of HD. This
      differential regulation may play a role in the pathophysiology of altered energy
      metabolism.

PMID- 24566951
TI  - T1 mapping in ischaemic heart disease.
AB  - A unique feature of cardiac magnetic resonance is its ability to characterize
      myocardium. Proton relaxation times, T1, T2, and T2* are a reflection of the
      composition of individual tissues, and change in the presence of disease.
      Research into T1 mapping has largely been focused in the study of
      cardiomyopathies, but T1 mapping also shows huge potential in the study of
      ischaemic heart disease. In fact, the first cardiac T1 maps were used to
      characterize myocardial infarction. Robust high-resolution myocardial T1 mapping
      is now available for use as a clinical tool. This quantitative technique is
      simple to perform and analyse, minimally subjective, and highly reproducible.
      This review aims to summarize the present state of research on the topic, and to
      show the clinical potential of this method to aid the diagnosis and treatment of
      patients with ischaemic heart disease. 

PMID- 24566952
TI  - A new paradigm of neuromuscular electrical stimulation for the quadriceps femoris
      muscle.
AB  - PURPOSE: Neuromuscular electrical stimulation (NMES) with large electrodes and
      multiple current pathways (m-NMES) has recently been proposed as a valid
      alternative to conventional NMES (c-NMES) for quadriceps muscle (re)training. The
      main aim of this study was to compare discomfort, evoked force and fatigue
      between m-NMES and c-NMES of the quadriceps femoris muscle in healthy subjects.
      METHODS: Ten healthy subjects completed two experimental sessions (c-NMES and m
      NMES), that were randomly presented in a cross-over design. Maximal electrically
      evoked force at pain threshold, self-reported discomfort at different levels of
      evoked force, and fatigue-induced force declines during and following a series of
      20 NMES contractions were compared between c-NMES and m-NMES. RESULTS: m-NMES
      resulted in greater evoked force (P < 0.05) and lower discomfort in comparison to
      c-NMES (P < 0.05-0.001), but fatigue time course and magnitude did not differ
      between the two conditions. CONCLUSIONS: The use of quadriceps m-NMES appears
      legitimate for (re)training purposes because it generated stronger contractions
      and was less discomfortable than c-NMES (due to multiple current pathways and/or
      lower current density with larger electrodes).

PMID- 24566953
TI  - Glomerular disease: frequency of podocyte-related gene mutations in FSGS.

PMID- 24566954
TI  - Transplantation: pulsatile perfusion-time for a prospective trial.
AB  - Pulsatile perfusion is increasingly being used to preserve kidneys harvested from
      non-standard-criteria donors. Indeed, retrospective analyses have shown that
      machine preservation is associated with reduced rates of delayed graft function.
      However, well-designed prospective clinical trials are needed to evaluate its
      impact on organ discard, rejection, long-term graft function, and cost.

PMID- 24566955
TI  - Anaemia: mutations in C5 explain eculizumab resistance.

PMID- 24566956
TI  - Hypertension: treatment-resistant hypertension - a risk factor for ESRD.

PMID- 24566957
TI  - Tracking of cell nuclei for assessment of in vitro uptake kinetics in ultrasound
      mediated drug delivery using fibered confocal fluorescence microscopy.
AB  - PURPOSE: Previously, we demonstrated the feasibility to monitor ultrasound
      mediated uptake of a cell-impermeable model drug in real time with fibered
      confocal fluorescence microscopy. Here, we present a complete post-processing
      methodology, which corrects for cell displacements, to improve the accuracy of
      pharmacokinetic parameter estimation. PROCEDURES: Nucleus detection was performed
      based on the radial symmetry transform algorithm. Cell tracking used an iterative
      closest point approach. Pharmacokinetic parameters were calculated by fitting a
      two-compartment model to the time-intensity curves of individual cells. RESULTS:
      Cells were tracked successfully, improving time-intensity curve accuracy and
      pharmacokinetic parameter estimation. With tracking, 93 % of the 370 nuclei
      showed a fluorescence signal variation that was well-described by a two
      compartment model. In addition, parameter distributions were narrower, thus
      increasing precision. CONCLUSIONS: Dedicated image analysis was implemented and
      enabled studying ultrasound-mediated model drug uptake kinetics in hundreds of
      cells per experiment, using fiber-based confocal fluorescence microscopy.

PMID- 24566958
TI  - Artifact removal in photoacoustic section imaging by combining an integrating
      cylindrical detector with model-based reconstruction.
AB  - Photoacoustic section imaging reveals optically absorbing structures within a
      thin slice of an object. It requires measuring acoustic waves excited by
      absorption of short laser pulses with a cylindrical acoustic lens detector
      rotating around the object. Owing to the finite detector size and its limited
      depth of focus, various artifacts arise, seen as distortions within the imaging
      slice and cross-talk from neighboring areas of the object. The presented solution
      aims at avoiding these artifacts by a special design of the sensor and by use of
      a model-based reconstruction algorithm that improves section images by
      incorporating information from neighboring sections. The integrating property of
      the cylindrical detector, which exceeds in direction of the cylinder axis the
      size of the imaged object, avoids the lateral blurring that normally results from
      the finite width of a small detector. Applying a maximum likelihood
      reconstruction method for the inversion of the imaging system matrix to the
      temporal pressure signals yields line projections of the initial energy
      distribution, from which section images are obtained by applying the inverse
      Radon transform. By using data from few sections, a significant reduction of
      artifacts related to the imperfections of the sensor is demonstrated both in
      simulations and in phantom experiments.

PMID- 24566959
TI  - New Ediacara fossils preserved in marine limestone and their ecological
      implications.
AB  - Ediacara fossils are central to our understanding of animal evolution on the eve
      of the Cambrian explosion, because some of them likely represent stem-group
      marine animals. However, some of the iconic Ediacara fossils have also been
      interpreted as terrestrial lichens or microbial colonies. Our ability to test
      these hypotheses is limited by a taphonomic bias that most Ediacara fossils are
      preserved in sandstones and siltstones. Here we report several iconic Ediacara
      fossils and an annulated tubular fossil (reconstructed as an erect epibenthic
      organism with uniserial arranged modular units), from marine limestone of the 551
      541 Ma Dengying Formation in South China. These fossils significantly expand the
      ecological ranges of several key Ediacara taxa and support that they are marine
      organisms rather than terrestrial lichens or microbial colonies. Their close
      association with abundant bilaterian burrows also indicates that they could
      tolerate and may have survived moderate levels of bioturbation. 

PMID- 24566960
TI  - Electrical inhomogeneity in left ventricular hypertrophy.
AB  - Recent studies designed to assess the relationship between aortic compliance and
      heterogeneity of heart electrical activity has shown that hypertrophy aggravates
      repolarization disturbances in the myocardium. Numerous mechanisms of electrical
      instability and inhomogeneity associated with left ventricular hypertrophy are
      now under investigation. Most of the studies have been found to be focused on
      ventricular Gradient, QT dispersion, amplitudes of isointegral maps during
      ventricular repolarization, abnormally low-QRST areas, dispersion of the QT
      interval, and spatial QRS-T(angle). These studies point to marked repolarization
      abnormalities in left ventricular hypertrophy and the dispersion of the QT
      interval as a valuable index for inhomogeneity of repolarization and the
      subsequent heart rate variability. The heart rate-corrected QT dispersion and QT
      apex dispersion seem to be significantly longer in the patients with left
      ventricular hypertrophy than in normal individuals. The review study has also
      identified QRST isointegral map as a valuable technique in assessment of the
      electro-cardiac events in LVH.

PMID- 24566961
TI  - TLR4 single nucleotide polymorphisms (SNPs) associated with Salmonella shedding
      in pigs.
AB  - Toll-like receptor 4 (TLR4) is a key factor in the innate immune recognition of
      lipopolysaccharide (LPS) from Gram-negative bacteria. Previous studies from our
      group identified differences in the expression profile of TLR4 and genes affected
      by the TLR4 signaling pathway among pigs that shed varying levels of Salmonella,
      a Gram-negative bacterium. Therefore, genetic variation in this gene may be
      involved with the host's immune response to bacterial infections. The current
      study screened for single nucleotide polymorphisms (SNPs) in the TLR4 gene and
      tested their association with Salmonella fecal shedding. Pigs (n = 117) were
      intranasally challenged at 7 weeks of age with 1 * 10(9) CFU of S. Typhimurium
      chi4232 and were classified as low or persistent Salmonella shedders based on the
      levels of Salmonella being excreted in fecal material. Salmonella fecal shedding
      was determined by quantitative bacteriology on days 2, 7, 14, and 20/21 post
      exposure, and the cumulative levels of Salmonella were calculated to identify the
      low (n = 20) and persistent (n = 20) Salmonella shedder pigs. From those 40
      animals, the TLR4 region was sequenced, and 18 single nucleotide polymorphisms
      (SNPs) in TLR4 were identified. Twelve SNPs have been previously described and
      six are novel SNPs of which five are in the 5' untranslated region and one is in
      intron 2. Single marker association test identified 13 SNPs associated with the
      qualitative trait of Salmonella fecal shedding, and seven of those SNPs were also
      associated with a quantitative measurement of fecal shedding (P < 0.05). Using a
      stepwise regression process, a haplotype composed of SNPs rs80787918 and
      rs80907449 (P <= 4.0 * 10(-3)) spanning a region of 4.9 Kb was identified,
      thereby providing additional information of the influence of those SNPs on
      Salmonella fecal shedding in pigs. 

PMID- 24566964
TI  - LCP distal ulna plate fixation of irreducible or unstable distal ulna fractures
      associated with distal radius fracture.
AB  - PURPOSE: The advent of locking compression plate (LCP) has provided convenient
      and secure fixation of distal ulna fractures. This study was performed to
      evaluate the functional and clinical outcomes following LCP distal ulna plate
      fixation of irreducible or unstable distal ulna fractures with concomitant distal
      radius fractures. METHODS: Retrospective review of 17 patients who had been
      treated with LCP distal ulna plates for distal ulna fractures was performed. The
      average age of the patients was 58.9 years (range 21-87 years), and the mean
      follow-up period was 15 months (range 12-20 months). This study consisted of
      eleven fractures involving metaphysis and six ulna styloid base fractures.
      Fracture union, radiologic parameters, stability of the distal radioulnar joint
      (DRUJ), and functional outcomes, including ROM, grip strength, and functional
      scores were evaluated. RESULTS: All patients showed bony union, the average
      radial height was 10.5 mm, and the ulnar variance was 0.8 mm on final
      radiographs. None of the patients had instability of the DRUJ compared with the
      opposite wrist, and the subluxation ratio was within normal range on the follow
      up CT scan. There were 6 excellent and 11 good cases according to Sarmiento's
      modified wrist score at the last follow-up. CONCLUSIONS: Locking compression
      plate distal ulna plate fixation of irreducible or unstable distal ulna fractures
      after stabilization of concomitant distal radius fractures showed favorable
      results in union, alignment, and functional outcomes and therefore could be one
      of the recommendable implant options for distal ulna fractures.

PMID- 24566965
TI  - Interpretation and reporting multiparametric prostate MRI: a primer for residents
      and novices.
AB  - Multiparametric MRI has developed as a tool for prostate cancer lesion detection,
      characterization, staging, surveillance, and imaging of local recurrence. Given
      the disease frequency and the growing importance of imaging, as reliance on PSA
      declines, radiologists involved in prostate MRI imaging must become proficient
      with the fundamentals of multiparametric prostate MRI (T2WI, DWI, DCE-MRI, and MR
      spectroscopy). Interpretation and reporting must yield accuracy, consistency, and
      add value to clinical care. This review provides a primer to novices and trainees
      learning about multiparametric prostate MRI. MRI technique is presented along
      with the use of particular MRI sequences. Relevant prostate anatomy is outlined
      and imaging features of prostate cancer with staging are discussed. Finally
      structured reporting is introduced, and some limitations of prostate MRI are
      discussed. 

PMID- 24566962
TI  - The application of genome-wide SNP genotyping methods in studies on livestock
      genomes.
AB  - Animal genomics is currently undergoing dynamic development, which is driven by
      the flourishing of high-throughput genome analysis methods. Recently, a large
      number of animals has been genotyped with the use of whole-genome genotyping
      assays in the course of genomic selection programmes. The results of such
      genotyping can also be used for studies on different aspects of livestock genome
      functioning and diversity. In this article, we review the recent literature
      concentrating on various aspects of animal genomics, including studies on linkage
      disequilibrium, runs of homozygosity, selection signatures, copy number variation
      and genetic differentiation of animal populations. Our work is aimed at providing
      insight into certain achievements of animal genomics and to arouse interest in
      basic research on the complexity and structure of the genomes of livestock. 

PMID- 24566966
TI  - Assessment of instream foam formation and quantification of foam in effluents.
AB  - Although the foam formation on surface waters nowadays is not comparable with the
      foam "mountains" in the 1970s, it still is an issue of water quality concern. A
      drawback in the discussion is the lack of methods to assess instream foam
      formation and foam emitted by point sources. Foam formation on a transboundary
      river in Austria led to an intensive study resulting in two parameters to
      quantify instream and emitted foam. Foam potential is introduced as emission
      parameter that is defined as flow rate of river water, which can foam due to an
      effluent's discharge. The foam index (FI) represents a parameter to assess the
      foam on the river and allows a semi-quantitative differentiation between the
      varying foaming conditions. This publication will present the developed methods
      and show some results to prove their accuracy and applicability. 

PMID- 24566967
TI  - Occurrence and abundance of tetracycline, sulfonamide resistance genes, and class
      1 integron in five wastewater treatment plants.
AB  - To understand the transport and fate of antibiotic resistance genes in wastewater
      treatment plants, 12 resistance genes (ten tetracycline resistance genes, two
      sulfonamides genes) and class 1 integron gene (intI1) were studied in five
      wastewater treatment plants with different treatment processes and different
      sewage sources. Among these resistance genes, sulfonamides genes (sul1 and sul2)
      were of the most prevalent genes with detection frequency of 100%. The effluent
      water contained fewer types of resistance genes than the influent in most
      selected plants. The abundance of five quantified resistance genes (tetG, tetW,
      tetX, sul1, and intI1) decreased in effluent of plants treating domestic or
      industrial wastewater with anaerobic/aerobic or membrane bioreactor (MBR)
      technologies, but tetG, tetX, sul1, and intI1 increased along the treatment units
      of plants treating vitamin C production wastewater by anaerobic/aerobic
      technology. In plant treating cephalosporins production wastewater by
      UASB/aerobic process, the quantities of tetG, tetX, and sul1 first decreased in
      anaerobic effluent water but then increased in aerobic effluent water.

PMID- 24566968
TI  - A comparative study of metal pollution and potential eco-risk in the sediment of
      Chaohu Lake (China) based on total concentration and chemical speciation.
AB  - Total and extractable concentrations of Cu, Pb, and Zn were determined in surface
      sediments of west Chaohu Lake (China) by HCl-HNO3-HF-HClO4 digestion and an
      optimized BCR sequential extraction procedure, respectively. The metal pollution
      was evaluated by the enrichment factor approach, and the potential eco-risk was
      evaluated by the sediment quality guideline (SQG) and risk assessment code (RAC)
      assessments. The results indicated that both total and extractable metal
      concentrations were highly variable and were affected by sediment properties,
      even though the sediments were predominantly composed of <63-MUm particles
      (>89%). Enrichment factors of the metals based on the total and extractable
      concentrations all showed higher values in the northern lake area and decreasing
      values towards the south. This distribution indicated an input of anthropogenic
      metals via the Nanfei River. Anthropogenic Cu, Pb, and Zn in surface sediments
      showed comparable values for each metal based on the total and extractable
      concentrations, suggesting that anthropogenic Cu, Pb, and Zn resided
      predominantly in the extractable fractions. Sediment Cu had low eco-risk, and Pb
      and Zn had medium eco-risk by the SQG assessment, whereas the eco-risk rankings
      of Cu, Pb, and Zn were medium, low, and low-high, respectively, by the RAC
      assessment. Referencing to the labile (dilute acid soluble) metal concentrations,
      we deduced that the eco-risk of Cu may be largely overestimated by the RAC
      assessment, and the eco-risk of Pb may be largely overestimated by the SQG
      assessment. Overall, sediments Cu and Pb may pose low eco-risk, and Zn may pose
      low-high eco-risk.

PMID- 24566969
TI  - Facile synthesis of magnetic ZnFe2O4-reduced graphene oxide hybrid and its photo
      Fenton-like behavior under visible iradiation.
AB  - A magnetic ZnFe2O4-reduced graphene oxide (rGO) hybrid was successfully developed
      as a heterogeneous catalyst for photo-Fenton-like decolorization of various dyes
      using peroxymonosulfate (PMS) as an oxidant under visible light irradiation.
      Through an in situ chemical deposition and reduction, ZnFe2O4 nanoparticles (NPs)
      with an average size of 23.7 nm were anchored uniformly on rGO sheets to form a
      ZnFe2O4-rGO hybrid. The catalytic activities in oxidative decomposition of
      organic dyes were evaluated. The reaction kinetics, effect of ion species and
      strength, catalytic stability, degradation mechanism, as well as the roles of
      ZnFe2O4 and graphene were also studied. ZnFe2O4-rGO showed to be a promising
      photocatalyst with magnetism for the oxidative degradation of aqueous organic
      pollutants and simple separation. The combination of ZnFe2O4 NPs with graphene
      sheets leads to a much higher catalytic activity than pure ZnFe2O4. Graphene
      acted as not only a support and stabilizer for ZnFe2O4 to prevent them from
      aggregation, largely improving the charge separation in the hybrid material, but
      also a catalyst for activating PMS to produce sulfate radicals at the same time.
      The ZnFe2O4-rGO hybrid exhibited stable performance without losing activity after
      five successive runs. 

PMID- 24566970
TI  - Determination of picogram quantities of chlortoluron in soil samples by luminol
      chitosan chemiluminescence system.
AB  - Based on the enhancing effect of chitosan (CS) on luminol-dissolved oxygen
      chemiluminescence (CL) reaction, a flow injection (FI) luminol-CS CL system was
      established. It was found that the increase of CL intensity was proportional to
      the concentrations of CS ranging from 0.7 to 10.0 MUmol l(-1). In the presence of
      chlortoluron (CTU), the CL intensity of luminol-CS system could be obviously
      inhibited and the decrements of CL intensity were linearly proportional to the
      logarithm of CTU concentrations ranging from 0.01 to 70.0 ng ml(-1), giving the
      limit of detection 3.0 pg ml(-1) (3sigma). At a flow rate of 2.0 ml min(-1), the
      whole process including sampling and washing could be accomplished within 36 s,
      offering a sample throughput of 100 h(-1). The proposed FI-CL method was
      successfully applied to the determination of CTU in soil samples with recoveries
      ranging from 95.0 % to 105.3 % and the relative standard deviations (RSDs) of
      less than 4.0 %.

PMID- 24566971
TI  - High levels of activity of bats at gold mining water bodies: implications for
      compliance with the International Cyanide Management Code.
AB  - Wildlife and livestock are known to visit and interact with tailings dam and
      other wastewater impoundments at gold mines. When cyanide concentrations within
      these water bodies exceed a critical toxicity threshold, significant cyanide
      related mortality events can occur in wildlife. Highly mobile taxa such as birds
      are particularly susceptible to cyanide toxicosis. Nocturnally active bats have
      similar access to uncovered wastewater impoundments as birds; however, cyanide
      toxicosis risks to bats remain ambiguous. This study investigated activity of
      bats in the airspace above two water bodies at an Australian gold mine, to assess
      the extent to which bats use these water bodies and hence are at potential risk
      of exposure to cyanide. Bat activity was present on most nights sampled during
      the 16-month survey period, although it was highly variable across nights and
      months. Therefore, despite the artificial nature of wastewater impoundments at
      gold mines, these structures present attractive habitats to bats. As tailings
      slurry and supernatant pooling within the tailings dam were consistently well
      below the industry protective concentration limit of 50 mg/L weak acid
      dissociable (WAD) cyanide, wastewater solutions stored within the tailings dam
      posed a minimal risk of cyanide toxicosis for wildlife, including bats. This
      study showed that passively recorded bat echolocation call data provides evidence
      of the presence and relative activity of bats above water bodies at mine sites.
      Furthermore, echolocation buzz calls recorded in the airspace directly above
      water provide indirect evidence of foraging and/or drinking. Both echolocation
      monitoring and systematic sampling of cyanide concentration in open wastewater
      impoundments can be incorporated into a gold mine risk-assessment model in order
      to evaluate the risk of bat exposure to cyanide. In relation to risk minimisation
      management practices, the most effective mechanism for preventing cyanide
      toxicosis to wildlife, including bats, is capping the concentration of cyanide in
      tailings discharged to open impoundments at 50 mg/L WAD. 

PMID- 24566977
TI  - Social media in health professional education: a student perspective on user
      levels and prospective applications.
AB  - Social Networking Sites (SNS) have seen exponential growth in recent years. The
      high utilisation of SNS by tertiary students makes them an attractive tool for
      educational institutions. This study aims to identify health professional
      students' use and behaviours with SNS, including students' perspectives on
      potential applications within health professional curricula. Students enrolled in
      an undergraduate physiotherapy program were invited to take part in an anonymous,
      online questionnaire at the end of 2012. The survey consisted of 20 items,
      gathering demographic data, information on current use of SNS, and opinions
      regarding the application of SNS into education. Both quantitative and
      qualitative data were gathered. A total of 142 students, from all years of study,
      completed the online questionnaire. Only two participants were not current users
      of social media. Facebook and YouTube had been utilised for educational purposes
      by 97 and 60 % of participants respectively; 85 % believed that SNS could benefit
      their learning experience. Only five respondents were not interested in following
      peers, academic staff, clinicians or professional associations on Facebook. Four
      key themes emerged: peer collaboration, need for separation between personal and
      professional realms, complimentary learning and enhanced communication. Students
      wish to make educational connections via SNS, yet expressed a strong desire to
      maintain privacy, and a distinction between personal and professional lives.
      Educational utilisation of SNS may improve communication speed and accessibility.
      Any educator involvement should be viewed with caution.

PMID- 24566975
TI  - CaV2.2 channel cell surface expression is regulated by the light chain 1 (LC1) of
      the microtubule-associated protein B (MAP1B) via UBE2L3-mediated ubiquitination
      and degradation.
AB  - Microtubule-associated protein B is a cytoskeleton protein consisting of heavy
      and light (LC) chains that play important roles in the regulation of neuronal
      morphogenesis and function. LC1 is also well known to interact with diverse
      ionotropic receptors at postsynapse. Much less is known, however, regarding the
      role of LC1 at presynaptic level where voltage-gated N-type Ca(2+) channels
      couple membrane depolarization to neurotransmitter release. Here, we investigated
      whether LC1 interacts with the N-type channels. Co-localization analysis revealed
      spatial proximity of the two proteins in hippocampal neurons. The interaction
      between LC1 and the N-type channel was demonstrated using co-immunoprecipitation
      experiments and in vitro pull-down assays. Detailed biochemical analysis
      suggested that the interaction occurs through the N-terminal of LC1 and the C
      terminal of the pore-forming CaValpha1 subunit of the channels. Patch-clamp
      studies in HEK-293 cells revealed a significant decrease in N-type currents upon
      LC1 expression, without apparent changes in kinetics. Recordings performed in the
      presence of MG132 prevented the actions of LC1 suggesting enhanced channel
      proteasomal degradation. Interestingly, using the yeast two-hybrid system and
      immunoprecipitation assays in HEK-293 cells, we revealed an interaction between
      LC1 and the ubiquitin-conjugating enzyme UBE2L3. Furthermore, we found that the
      LC1/UBE2L3 complex could interact with the N-type channels, suggesting that LC1
      may act as a scaffold protein to increase UBE2L3-mediated channel ubiquitination.
      Together these results revealed a novel functional coupling between LC1 and the N
      type channels. 

PMID- 24566978
TI  - Enhanced photocatalytic performance of TiO2-ZnO hybrid nanostructures.
AB  - We studied the photocatalytic properties of rational designed TiO2-ZnO hybrid
      nanostructures, which were fabricated by the site-specific deposition of
      amorphous TiO2 on the tips of ZnO nanorods. Compared with the pure components of
      ZnO nanorods and amorphous TiO2 nanoparticles, these TiO2-ZnO hybrid
      nanostructures demonstrated a higher catalytic activity. The strong green
      emission quenching observed from photoluminescence of TiO2-ZnO hybrid
      nanostructures implied an enhanced charge transfer/separation process resulting
      from the novel type II heterostructures with fine interfaces. The catalytic
      performance of annealing products with different TiO2 phase varied with the
      annealing temperatures. This is attributed to the combinational changes in Eg of
      the TiO2 phase, the specific surface area and the quantity of surface hydroxyl
      groups. 

PMID- 24566976
TI  - Gene therapies for arrhythmias in heart failure.
AB  - In this article, we review recent advances in our understanding of arrhythmia
      mechanisms in the failing heart. We focus on changes in repolarization,
      conduction, and intracellular calcium cycling because of their importance to the
      vast majority of clinical arrhythmias in heart failure. We highlight recent
      efforts to combat arrhythmias using gene-based approaches that target ion
      channel, gap junction, and calcium cycling proteins. We further discuss the
      advantages and limitations associated with individual approaches. 

PMID- 24566980
TI  - Artery of Percheron infarction as an unusual cause of coma: three cases and
      literature review.
AB  - OBJECTIVE: Stroke due to occlusion of the artery of Percheron (AOP), an uncommon
      anatomic variant supplying the bilateral medial thalami, may raise diagnostic
      challenges and cause life-threatening symptoms. Our objective here was to detail
      the features and outcomes in three patients who required intensive care unit
      (ICU) admission and to review the relevant literature. METHODS: Description of
      three cases and literature review based on a 1973-2013 PubMed search. RESULTS:
      Three patients were admitted to our ICU with sudden-onset coma and respiratory
      and cardiovascular dysfunctions requiring endotracheal mechanical ventilation.
      Focal neurological deficits, ophthalmological signs (abnormal light reflexes
      and/or ocular motility and/or ptosis), and neuropsychological abnormalities were
      variably combined. Initial CT scan was normal. Cerebral MRI demonstrated
      bilateral paramedian thalamic infarction, with extension to the cerebral
      peduncles in two patients. Consciousness improved rapidly and time to extubation
      was 1-4 days. All three patients were discharged alive from the hospital and two
      had good 1-year functional outcomes. Similar clinical features and outcomes were
      recorded in the 117 patients identified in the literature, of whom ten required
      ICU admission. CONCLUSIONS: Bilateral paramedian thalamic stroke due to AOP
      occlusion can be life threatening. The early diagnosis relies on MRI with
      magnetic resonance angiography. Recovery of consciousness is usually rapid and
      mortality is low, warranting full-code ICU management.

PMID- 24566979
TI  - Intraventricular fibrinolysis has no effects on shunt dependency and functional
      outcome in endovascular-treated aneurysmal SAH.
AB  - BACKGROUND: Intraventricular fibrinolysis (IVF) in subarachnoid hemorrhage (SAH)
      is an emerging strategy aiming to hasten clot lysis, treat hydrocephalus, and
      reduce permanent shunt rates. Because of clinical heterogeneity of investigated
      patient effects of IVF on permanent shunt incidence and functional outcome are
      widely debated. The present study is the first to investigate solely endovascular
      treated SAH patients. METHODS: Overall, 88 consecutive patients with aneurysmal
      SAH requiring external ventricular drain placement and endovascular aneurysm
      closure were included. Functional outcome and shunt dependency were assessed 90
      days after event. A matched controlled sub-analysis was carried out to
      investigate the effects of IVF treatment (n = 14; matching criteria: age, neuro
      status and imaging). Multivariate modeling was performed to identify independent
      predictors for permanent shunt dependency. RESULTS: In IVF-patients neurological
      status was significantly poorer [Hunt&Hess: IVF = 4(3-5) vs. non-IVF = 3(1-5); p
      = 0.035] and the extent of ventricular hemorrhage was increased [Graeb Score: IVF
      = 7(6-8) vs. non-IVF = 3(1-4); p <= 0.001]. Consecutive matched controlled sub
      analysis revealed no significant therapeutic effect of IVF with respect to shunt
      dependency rate and functional outcome. Multivariate analysis revealed Graeb
      score [OR = 1.34(1.02-1.76); p = 0.035] and sepsis [OR = 11.23(2.28-55.27); p =
      0.003] as independent predictors for shunt dependency, whereas IVF did not exert
      significant effects (p = 0.820). CONCLUSIONS: In endovascular-treated SAH
      patients IVF neither reduced permanent shunt dependency nor influenced functional
      outcome. Despite established effects on intraventricular clot resolution IVF
      appears less powerful in SAH as compared to ICH. Given the reported positive
      effects of lumbar drainage (LD) in SAH, a prospective analysis of a combined
      treatment approach of IVF and subsequent lumbar drain sOeems warranted aiming to
      reduce permanent shunting and improve functional outcome.

PMID- 24566981
TI  - Neurocritical care in Germany: need for guidance.

PMID- 24566982
TI  - The management of hip fracture in the older population. Joint position statement
      by Gruppo Italiano Ortogeriatria (GIOG).
AB  - This document is a Joint Position Statement by Gruppo Italiano di OrtoGeriatria
      (GIOG) supported by Societa Italiana di Gerontologia e Geriatria (SIGG), and
      Associazione Italiana Psicogeriatria (AIP) on management of hip fracture older
      patients. Orthogeriatric care is at present the best model of care to improve
      results in older patients after hip fracture. The implementation of
      orthogeriatric model of care, based on the collaboration between orthopaedic
      surgeons and geriatricians, must take into account the local availability of
      resources and facilities and should be integrated into the local context. At the
      same time the programme must be based on the best available evidences and planned
      following accepted quality standards that ensure the efficacy of the
      intervention. The position paper focused on eight quality standards for the
      management of hip fracture older patients in orthogeriatric model of care. The
      GIOG promotes the development of a clinic database with the aim of obtaining a
      qualitative improvement in the management of hip fracture. 

PMID- 24566983
TI  - Increased risk of acute cardiovascular events after partner bereavement: a
      matched cohort study.
AB  - IMPORTANCE The period immediately after bereavement has been reported as a time
      of increased risk of cardiovascular events. However, this risk has not been well
      quantified, and few large population studies have examined partner bereavement.
      OBJECTIVE To compare the rate of cardiovascular events between older individuals
      whose partner dies with those of a matched control group of individuals whose
      partner was still alive on the same day. DESIGN, SETTING, AND PARTICIPANTS
      Matched cohort study using a UK primary care database containing availale data of
      401 general practices from February 2005 through September 2012. In all, 30 447
      individuals aged 60 to 89 years at study initiation who experienced partner
      bereavement during follow-up were matched by age, sex, and general practice with
      the nonbereaved control group (n = 83 588) at the time of bereavement. EXPOSURES
      Partner bereavement. MAIN OUTCOMES AND MEASURES The primary outcome was
      occurrence of a fatal or nonfatal myocardial infarction (MI) or stroke within 30
      days of bereavement. Secondary outcomes were non-MI acute coronary syndrome and
      pulmonary embolism. All outcomes were compared between the groups during
      prespecified periods after bereavement (30, 90, and 365 days). Incidence rate
      ratios (IRRs) from a conditional Poisson model were adjusted for age, smoking
      status, deprivation, and history of cardiovascular disease. RESULTS Within 30
      days of their partner's death, 50 of the bereaved group (0.16%) experienced an MI
      or a stroke compared with 67 of the matched nonbereaved controls (0.08%) during
      the same period (IRR, 2.20 [95% CI, 1.52-3.15]). The increased risk was seen in
      bereaved men and women and attenuated after 30 days. For individual outcomes, the
      increased risk was found separately for MI (IRR, 2.14 [95% CI, 1.20-3.81]) and
      stroke (2.40 [1.22-4.71]). Associations with rarer events were also seen after
      bereavement, including elevated risk of non-MI acute coronary syndrome (IRR, 2.20
      [95% CI, 1.12-4.29]) and pulmonary embolism (2.37 [1.18-4.75]) in the first 90
      days. CONCLUSIONS AND RELEVANCE This study provides further evidence that the
      death of a partner is associated with a range of major cardiovascular events in
      the immediate weeks and months after bereavement. Understanding psychosocial
      factors associated with acute cardiovascular events may provide opportunities for
      prevention and improved clinical care. 

PMID- 24566985
TI  - Bacterial spores survive electrospray charging and desolvation.
AB  - The survivability of Bacillus subtilis spores and vegetative Escherichia coli
      cells after electrospray from aqueous suspension was tested using mobility
      experiments at atmospheric pressure. E. coli did not survive electrospray
      charging and desolvation, but B. subtilis did. Experimental conditions ensured
      that any surviving bacteria were de-agglomerated, desolvated, and electrically
      charged. Based on mobility measurements, B. subtilis spores survived even with
      2,000-20,000 positive charges. B. subtilis was also found to survive introduction
      into vacuum after either positive or negative electrospray. Attempts to measure
      the charge distribution of viable B. subtilis spores using electrostatic
      deflection in vacuum were inconclusive; however, viable spores with low charge
      states (less than 42 positive or less than 26 negative charges) were observed. 

PMID- 24566986
TI  - Prediction and stratification of upper limb function and self-care in acute
      cervical spinal cord injury with the graded redefined assessment of strength,
      sensibility, and prehension (GRASSP).
AB  - BACKGROUND: There is inherent heterogeneity within individuals suffering from
      cervical spinal cord injury (SCI), and early prediction of upper limb function
      and self-care is challenging. As a result, considerable uncertainty exists
      regarding the prediction of functional outcome following cervical SCI within 1
      year of injury. OBJECTIVE: To evaluate the value of Graded Redefined Assessment
      of Strength, Sensibility, and Prehension (GRASSP) in predicting upper limb
      function and self-care outcomes in individuals with cervical SCI. METHOD: A
      prospective longitudinal multicenter study was performed. Data from the GRASSP,
      the Spinal Cord Independence Measure (SCIM III), and the American Spinal Injury
      Association (ASIA) Impairment Scale were recorded at 1, 6, and 12 months after
      cervical SCI. For prediction of functional outcome at 6 and 12 months, a logistic
      regression model, receiver operating characteristics (ROC), and unbiased
      recursive partitioning conditional inference tree (URP-CTREE) were used with 8
      different predictor variables. RESULTS: Logistic regression analysis, ROC
      analysis, and URP-CTREE all revealed that the strength subtest within GRASSP is
      the strongest predictor for upper limb function and self-care outcomes. URP-CTREE
      provides useful information on the distribution of different outcomes in acute
      cervical SCI and can be used to predict cohorts with homogeneous outcomes.
      CONCLUSION: The GRASSP at 1 month can accurately predict upper limb function and
      self-care outcomes even in a heterogeneous group of individuals across a wide
      spectrum of neurological recovery. The application of URP-CTREE can reveal the
      distribution of outcome categories and, based on this, inform trial protocols
      with respect to outcomes analysis and patient stratification.

PMID- 24566984
TI  - Inhibition of receptor signaling and of glioblastoma-derived tumor growth by a
      novel PDGFRbeta aptamer.
AB  - Platelet-derived growth factor receptor beta (PDGFRbeta) is a cell-surface
      tyrosine kinase receptor implicated in several cellular processes including
      proliferation, migration, and angiogenesis. It represents a compelling
      therapeutic target in many human tumors, including glioma. A number of tyrosine
      kinase inhibitors under development as antitumor agents have been found to
      inhibit PDGFRbeta. However, they are not selective as they present multiple
      tyrosine kinase targets. Here, we report a novel PDGFRbeta-specific antagonist
      represented by a nuclease-resistant RNA-aptamer, named Gint4.T. This aptamer is
      able to specifically bind to the human PDGFRbeta ectodomain (Kd: 9.6 nmol/l)
      causing a strong inhibition of ligand-dependent receptor activation and of
      downstream signaling in cell lines and primary cultures of human glioblastoma
      cells. Moreover, Gint4.T aptamer drastically inhibits cell migration and
      proliferation, induces differentiation, and blocks tumor growth in vivo. In
      addition, Gint4.T aptamer prevents PDGFRbeta heterodimerization with and
      resultant transactivation of epidermal growth factor receptor. As a result, the
      combination of Gint4.T and an epidermal growth factor receptor-targeted aptamer
      is better at slowing tumor growth than either single aptamer alone. These
      findings reveal Gint4.T as a PDGFRbeta-drug candidate with translational
      potential. 

PMID- 24566987
TI  - Illusory touch temporarily improves sensation in areas of chronic numbness: a
      brief communication.
AB  - BACKGROUND: Creating the visual illusion of touch can improve tactile perception
      in healthy subjects. OBJECTIVE: We were interested in seeing if creating the
      illusion of touch in an insensate area could improve sensation in that area.
      METHODS: Fourteen people with chronic numbness participated in a randomized
      crossover experiment. The 4 conditions were the following: (a) stimulation over
      the unaffected limb with mirror visual feedback (experimental condition), (b)
      stimulation over the affected limb with mirror visual feedback, (c) stimulation
      over the unaffected limb without mirror visual feedback, and (d) stimulation over
      the affected limb without mirror visual feedback. Participants were assessed
      before and after each condition using the Ten-Test and mechanical detection
      thresholds. Data were analyzed using linear mixed models. RESULT: Only the
      experimental condition produced a change in the Ten-Test (mean difference = -1.1;
      95% confidence interval = -1.8 to -0.4; P = .003), corresponding to a 24%
      improvement in sensation. No differences were observed for any condition in
      mechanical detection thresholds. CONCLUSION: Creating the illusion of touch may
      improve sensory function in areas of chronic numbness. This preliminary finding
      adds to the growing body of evidence supporting the use of techniques that
      directly target cortical function in people with peripheral nerve injury.

PMID- 24566988
TI  - Origin plasticity during budding yeast DNA replication in vitro.
AB  - The separation of DNA replication origin licensing and activation in the cell
      cycle is essential for genome stability across generations in eukaryotic cells.
      Pre-replicative complexes (pre-RCs) license origins by loading Mcm2-7 complexes
      in inactive form around DNA. During origin firing in S phase, replisomes assemble
      around the activated Mcm2-7 DNA helicase. Budding yeast pre-RCs have previously
      been reconstituted in vitro with purified proteins. Here, we show that
      reconstituted pre-RCs support replication of plasmid DNA in yeast cell extracts
      in a reaction that exhibits hallmarks of cellular replication initiation. Plasmid
      replication in vitro results in the generation of covalently closed circular
      daughter molecules, indicating that the system recapitulates the initiation,
      elongation, and termination stages of DNA replication. Unexpectedly, yeast origin
      DNA is not strictly required for DNA replication in vitro, as heterologous DNA
      sequences could support replication of plasmid molecules. Our findings support
      the notion that epigenetic mechanisms are important for determining replication
      origin sites in budding yeast, highlighting mechanistic principles of replication
      origin specification that are common among eukaryotes. 

PMID- 24566990
TI  - The effects of standard electrical PV isolation vs. "pace and ablate" on ATP
      provoked PV reconnections.
AB  - BACKGROUND: Catheter ablation procedures for atrial fibrillation (AF) often
      involve circumferential pulmonary vein isolation (PVI). Lack of reliable
      identification of conduction gaps along the ablation line necessitates additional
      ablation within previous lesion sets. We conducted a retrospective comparative
      study to determine the best PVI strategy for prevention of PV reconnections.
      METHODS AND RESULTS: We compared the outcomes of PVI performed in two groups of
      patients with AF: those in whom a three-dimensional mapping system and irrigated
      tip radiofrequency catheter were used to electrically isolate the ipsilateral PVs
      (31 patients, electrical isolation group) and those in whom "pace and ablate" was
      performed in the PV antra until pacing at 10 mA and 2 ms no longer captured the
      atrial myocardium along the ablation line (31 patients, pace and ablate group). A
      bolus administration of 30 mg of adenosine triphosphate (ATP) revealed dormant PV
      reconnections more frequently in the electrical isolation group than in the pace
      and ablate group (28 [90%] of 31 patients vs. 16 [52%] of 31 patients, p =
      0.0005). After re-isolation of the sites of dormant PV conduction, the post
      ablation recurrence rates at 1 year were similar (26 vs. 26%, p = 1.000).
      CONCLUSION: Electrical PVI can usually be achieved without complete
      circumferential ablation. However, the isolated PVs often show dormant
      conduction. These findings support the hypothesis that reversible tissue injury
      contributes to PVI that may be acute but not necessarily durable. Similar
      outcomes between the two ablation strategies suggest that ATP provocation tests
      remain necessary to unmask dormant PV conduction.

PMID- 24566989
TI  - Prereplicative complexes assembled in vitro support origin-dependent and
      independent DNA replication.
AB  - Eukaryotic DNA replication initiates from multiple replication origins. To ensure
      each origin fires just once per cell cycle, initiation is divided into two
      biochemically discrete steps: the Mcm2-7 helicase is first loaded into
      prereplicative complexes (pre-RCs) as an inactive double hexamer by the origin
      recognition complex (ORC), Cdt1 and Cdc6; the helicase is then activated by a set
      of "firing factors." Here, we show that plasmids containing pre-RCs assembled
      with purified proteins support complete and semi-conservative replication in
      extracts from budding yeast cells overexpressing firing factors. Replication
      requires cyclin-dependent kinase (CDK) and Dbf4-dependent kinase (DDK). DDK
      phosphorylation of Mcm2-7 does not by itself promote separation of the double
      hexamer, but is required for the recruitment of firing factors and replisome
      components in the extract. Plasmid replication does not require a functional
      replication origin; however, in the presence of competitor DNA and limiting ORC
      concentrations, replication becomes origin-dependent in this system. These
      experiments indicate that Mcm2-7 double hexamers can be precursors of replication
      and provide insight into the nature of eukaryotic DNA replication origins. 

PMID- 24566991
TI  - Effect of supervised exercise training on musculoskeletal symptoms and function
      in patients with type 2 diabetes: the Italian Diabetes Exercise Study (IDES).
AB  - Musculoskeletal disorders are common in subjects with type 2 diabetes mellitus
      (T2DM) and may represent a barrier to physical activity (PA). In the Italian
      Diabetes and Exercise Study, we assessed whether a strategy aimed at minimizing
      the risk of injury and worsening of musculoskeletal symptoms favors participation
      in exercise training and results in improvements in joint-specific functional
      scores, along with amelioration of metabolic profile. Sedentary patients with
      T2DM (n = 606) from 22 outpatient diabetes clinics were randomized to twice-a
      week supervised aerobic and resistance training plus exercise counseling (EXE)
      versus counseling alone (CON) for 12 months. Musculoskeletal symptoms were
      evaluated at baseline in the entire cohort by the use of a self-reported
      questionnaire in order to design tailored exercise programs with exclusion of
      painful segments, and validated joint-specific scores were calculated at the end
      of study in a subgroup of CON (n = 65) and EXE subjects (n = 62). Musculoskeletal
      symptoms were present in more than 3/4 of EXE and CON subjects. Yet, volumes of
      non-supervised PA were high, whereas dropout rates and adverse events were low in
      both groups. Moreover, in the EXE group, no difference was observed between
      patients with and without symptoms in session attendance and PA/exercise volume.
      Scores for symptoms and functional status of limbs and spine were significantly
      better in EXE than in CON subjects and correlated with PA/exercise volume and
      improvements in fitness parameters. Preliminary evaluation of musculoskeletal
      symptoms is useful in favoring compliance with supervised training programs and
      obtaining significant benefits to the functional status of the involved joints. 

PMID- 24566992
TI  - Effect of tibial drill-guide angle on the mechanical environment at bone tunnel
      aperture after anatomic single-bundle anterior cruciate ligament reconstruction.
AB  - PURPOSE: The tibial drill-guide angle in anterior cruciate ligament (ACL)
      reconstruction influences the tunnel placement and graft-tunnel force, and is
      potentially associated with post-operative tunnel widening. This study aimed to
      examine the effect of the drill-guide angle on the stress redistribution at the
      tibial tunnel aperture after anatomic single-bundle ACL reconstruction. METHODS:
      A validated finite element model of human knee joint was used. The tibial tunnel
      with drill-guide angle ranging from 30 degrees  to 75 degrees  was investigated.
      The post-operative stress redistribution in tibia under the compressive, valgus,
      rotational and complex loadings was analysed. RESULTS: Compressive loading played
      a leading role on the stress redistribution at intra-articular tibial tunnel
      aperture. After ACL reconstruction, stress concentration occurred in the anterior
      and posterior regions of tunnel aperture while stress reduction occurred in the
      lateral and posteromedial regions under the compressive loading. Stress
      redistribution was partially alleviated by using the drill-guide angle ranging
      from 55 degrees  to 65 degrees . CONCLUSIONS: The present study quantified the
      effect of bone tunnel drill-guide angle on the post-operative stress
      redistribution. This phenomenon potentially contributed to tunnel widening. A
      tunnel drill-guide angle ranging from 55 degrees  to 65 degrees  was proposed
      based on the biomechanical rationale. It could serve as a helpful surgical guide
      for ACL reconstruction.

PMID- 24566993
TI  - From pericytes to perivascular tumours: correlation between pathology, stem cell
      biology, and tissue engineering.
AB  - PURPOSE: Pericytes were once thought only to aid in angiogenesis and blood
      pressure control. Gradually, the known functions of pericytes and other
      perivascular stem cells (PSC) have broadly increased. The following review
      article will summarize the known functions and importance of pericytes across
      disciplines of pathology, stem cell biology, and tissue engineering. METHODS: A
      literature review was performed for studies examining the importance of pericytes
      in pathology, stem cell biology, and tissue engineering. RESULTS: The importance
      of pericytes most prominently includes the identification of the perivascular
      identity of mesenchymal stem cells (or MSC). Now, pericytes and other PSC are
      known to display surface markers and multilineage differentiation potential of
      MSC. Accordingly, interest in the purification and use of PSC for mesenchymal
      tissue formation and regeneration has increased. Significant demonstration of in
      vivo efficacy in bone and muscle regeneration has been made in laboratory
      animals. Contemporaneously with the uncovering of an MSC identity for pericytes,
      investigators in tumour biology have found biologically relevant roles for
      pericytes in tumor formation, lymphovascular invasion, and perivascular tumor
      spread. As well, the contribution of pericytes to perivascular tumors has been
      examined (and debated), including glomus tumour, myopericytoma and solitary
      fibrous tumour/hemangiopericytoma. In addition, an expanding recognition of
      pericyte mimicry and perivascular tumour invasion has occurred, encompassing
      common malignancies of the brain and skin. CONCLUSIONS: In summary, pericytes
      have a wide range of roles in health and disease. Pericytes are being
      increasingly studied for their role in tumour formation, growth and invasion.
      Likewise, the application of pericytes/PSC for mesenchymal tissue engineering is
      an expanding field of interest.

PMID- 24566994
TI  - Ageing-related cardiomyocyte functional decline is sex and angiotensin II
      dependent.
AB  - Clinically, heart failure is an age-dependent pathological phenomenon and
      displays sex-specific characteristics. The renin-angiotensin system mediates
      cardiac pathology in heart failure. This study investigated the sexually
      dimorphic functional effects of ageing combined with angiotensin II (AngII) on
      cardiac muscle cell function, twitch and Ca(2+)-handling characteristics of
      isolated cardiomyocytes from young (~13 weeks) and aged (~87 weeks) adult wild
      type (WT) and AngII-transgenic (TG) mice. We hypothesised that AngII-induced
      contractile impairment would be exacerbated in aged female cardiomyocytes and
      linked to Ca(2+)-handling disturbances. AngII-induced cardiomyocyte hypertrophy
      was evident in young adult mice of both sexes and accentuated by age (aged adult
      ~21-23 % increases in cell length relative to WT). In female AngII-TG mice,
      ageing was associated with suppressed cardiomyocyte contractility (% shortening,
      maximum rate of shortening, maximum rate of relaxation). This was associated with
      delayed cytosolic Ca(2+) removal during twitch relaxation (Tau ~20 % increase
      relative to young adult female WT), and myofilament responsiveness to Ca(2+) was
      maintained. In contrast, aged AngII-TG male cardiomyocytes exhibited peak
      shortening equivalent to young TG; yet, myofilament Ca(2+) responsiveness was
      profoundly reduced with ageing. Increased pro-arrhythmogenic spontaneous activity
      was evident with age and cardiac AngII overexpression in male mice (42-55 % of
      myocytes) but relatively suppressed in female aged transgenic mice. Female
      myocytes with elevated AngII appear more susceptible to an age-related
      contractile deficit, whereas male AngII-TG myocytes preserve contractile function
      with age but exhibit desensitisation of myofilaments to Ca(2+) and a heightened
      vulnerability to arrhythmic activity. These findings support the contention that
      sex-specific therapies are required for the treatment of age-progressive heart
      failure.

PMID- 24566996
TI  - Nesting habits shape feeding preferences and predatory behavior in an ant genus.
AB  - We tested if nesting habits influence ant feeding preferences and predatory
      behavior in the monophyletic genus Pseudomyrmex (Pseudomyrmecinae) which
      comprises terrestrial and arboreal species, and, among the latter, plant-ants
      which are obligate inhabitants of myrmecophytes (i.e., plants sheltering so
      called plant-ants in hollow structures). A cafeteria experiment revealed that the
      diet of ground-nesting Pseudomyrmex consists mostly of prey and that of arboreal
      species consists mostly of sugary substances, whereas the plant-ants discarded
      all the food we provided. Workers forage solitarily, detecting prey from a
      distance thanks to their hypertrophied eyes. Approach is followed by antennal
      contact, seizure, and the manipulation of the prey to sting it under its thorax
      (next to the ventral nerve cord). Arboreal species were not more efficient at
      capturing prey than were ground-nesting species. A large worker size favors prey
      capture. Workers from ground- and arboreal-nesting species show several uncommon
      behavioral traits, each known in different ant genera from different subfamilies:
      leaping abilities, the use of surface tension strengths to transport liquids,
      short-range recruitment followed by conflicts between nestmates, the consumption
      of the prey's hemolymph, and the retrieval of entire prey or pieces of prey after
      having cut it up. Yet, we never noted group ambushing. We also confirmed that
      Pseudomyrmex plant-ants live in a kind of food autarky as they feed only on
      rewards produced by their host myrmecophyte, or on honeydew produced by the
      hemipterans they attend and possibly on the fungi they cultivate. 

PMID- 24566997
TI  - Assembly and loss of the polar flagellum in plant-associated methylobacteria.
AB  - On the leaf surfaces of numerous plant species, inclusive of sunflower
      (Helianthus annuus L.), pink-pigmented, methanol-consuming, phytohormone
      secreting prokaryotes of the genus Methylobacterium have been detected. However,
      neither the roles, nor the exact mode of colonization of these epiphytic microbes
      have been explored in detail. Using germ-free sunflower seeds, we document that,
      during the first days of seedling development, methylobacteria exert no promotive
      effect on organ growth. Since the microbes are evenly distributed over the outer
      surface of the above-ground phytosphere, we analyzed the behavior of populations
      taken from two bacterial strains that were cultivated as solid, biofilm-like
      clones on agar plates in different aqueous environments (Methylobacterium
      mesophilicum and M. marchantiae, respectively). After transfer into liquid
      medium, the rod-shaped, immobile methylobacteria assembled a flagellum and
      developed into planktonic microbes that were motile. During the linear phase of
      microbial growth in liquid cultures, the percentage of swimming, flagellated
      bacteria reached a maximum, and thereafter declined. In stationary populations,
      living, immotile bacteria, and isolated flagella were observed. Hence,
      methylobacteria that live in a biofilm, transferred into aqueous environments,
      assemble a flagellum that is lost when cell density has reached a maximum. This
      swimming motility, which appeared during ontogenetic development within growing
      microbial populations, may be a means to colonize the moist outer surfaces of
      leaves. 

PMID- 24566998
TI  - Genetics: Exome sequencing sheds light on hereditary spastic paraplegia.

PMID- 24567007
TI  - Lymphoepithelioma-like carcinoma of the stomach with incidental gastrointestinal
      stromal tumor (GIST)--a rare synchrony of two tumors.

PMID- 24567008
TI  - Soft plasmons with stretchable spectroscopic response based on thermally
      patterned gold nanoparticles.
AB  - Flexible photonic crystals are attractive devices owing to their multifold
      tunable parameters additionally introduced by soft substrates or by
      nanostructured, nano-doped, or nano-embedded soft matters. This not only extends
      significantly the intrinsic functions of photonic crystals, but also facilitates
      easy integration of the photonic crystal device into various optoelectronic and
      sensing systems. So far, flexible metallic photonic structures have been
      constructed on micrometer scales with complex fabrication procedures. Much
      simpler and more reproducible methods are expected to achieve such metamaterials
      in large scales and at low costs. In address to these challenges, we developed a
      straightforward approach to create soft plasmonic photonic crystals consisting of
      gold nanolines arranged on stretchable substrates with nanoscale periods,
      centimeter-scale areas, and high reproducibility using annealed gold nanoparticle
      colloids. 

PMID- 24567009
TI  - Off-label use of drugs in children.
AB  - The passage of the Best Pharmaceuticals for Children Act and the Pediatric
      Research Equity Act has collectively resulted in an improvement in rational
      prescribing for children, including more than 500 labeling changes. However, off
      label drug use remains an important public health issue for infants, children,
      and adolescents, because an overwhelming number of drugs still have no
      information in the labeling for use in pediatrics. The purpose of off-label use
      is to benefit the individual patient. Practitioners use their professional
      judgment to determine these uses. As such, the term "off-label" does not imply an
      improper, illegal, contraindicated, or investigational use. Therapeutic decision
      making must always rely on the best available evidence and the importance of the
      benefit for the individual patient. 

PMID- 24567010
TI  - Epidemiology of male genital abnormalities: a population study.
AB  - BACKGROUND: We conducted genital health wellness screens in male kindergarten
      children between the ages of 3 and 6 years to assess the incidence of congenital
      abnormalities and their treatment. METHODS: We performed genital examinations on
      2241 male children in 8 kindergartens. We screened for 4 conditions: phimosis,
      hypospadias, cryptorchidism, and hydrocele/hernia. We assessed the incidence of
      these conditions and the effectiveness or lack of their treatment. RESULTS: Among
      this sample, 55.5% children aged 3 to 4 years and 44.1% aged 5 to 6 years were
      found to have persistent phimosis. The circumcision rate, excluding those
      performed in conjunction with hypospadias repair, was 2.8%, but it carried a 3.2%
      complication rate. There was a lower incidence of hypospadias and cryptorchidism
      than reported in the literature at 0.2% and 0.4%, respectively. Our hypospadias
      repair rate was 60%, with a success rate of 66.7%. Our cryptorchidism repair rate
      was only 25%, and all repairs were performed above the age of 5 years. Incidence
      of hydrocele and hernias was 1.2%, and our treatment rate was 46.2%. Finally, we
      found high incidence of keloid formation, 73.3%, associated with inguinal
      incision. CONCLUSIONS: There was high prevalence of phimosis in Chinese boys, a
      natural physiologic condition, up to age 6. There appeared to be lower incidences
      of hypospadias and cryptorchidism in our screened population. However, there were
      opportunities for us to improve the diagnosis and treatment of these 2
      conditions. Our hydrocele/hernia incidence was on par with literature, but we had
      a lower treatment rate. Finally, we found a high incidence of keloid formation
      associated with inguinal incision.

PMID- 24567012
TI  - 2014 recommendations for pediatric preventive health care.

PMID- 24567011
TI  - Vaccine financing from the perspective of primary care physicians.
AB  - OBJECTIVES: Because of high purchase costs of newer vaccines, financial risk to
      private vaccination providers has increased. We assessed among pediatricians and
      family physicians satisfaction with insurance payment for vaccine purchase and
      administration by payer type, the proportion who have considered discontinuing
      provision of all childhood vaccines for financial reasons, and strategies used
      for handling uncertainty about insurance coverage when new vaccines first become
      available. METHODS: A national survey among private pediatricians and family
      physicians April to September 2011. RESULTS: Response rates were 69% (190/277)
      for pediatricians and 70% (181/260) for family physicians. Level of
      dissatisfaction varied significantly by payer type for payment for vaccine
      administration (Medicaid, 63%; Children's Health Insurance Program, 56%; managed
      care organizations, 48%; preferred provider organizations, 38%; fee for service,
      37%; P < .001), but not for payment for vaccine purchase (health maintenance
      organization or managed care organization, 52%; Child Health Insurance Program,
      47%; preferred provider organization, 45%; fee for service, 41%; P = .11). Ten
      percent of physicians had seriously considered discontinuing providing all
      childhood vaccines to privately insured patients because of cost issues. The most
      commonly used strategy for handling uncertainty about insurance coverage for new
      vaccines was to inform parents that they may be billed for the vaccine; 67% of
      physicians reported using 3 or more strategies to handle this uncertainty.
      CONCLUSIONS: Many primary care physicians are dissatisfied with payment for
      vaccine purchase and administration from third-party payers, particularly public
      insurance for vaccine administration. Physicians report a variety of strategies
      for dealing with the uncertainty of insurance coverage for new vaccines.

PMID- 24567014
TI  - Systematic review and meta-analyses: fever in pregnancy and health impacts in the
      offspring.
AB  - BACKGROUND AND OBJECTIVE: Fever during pregnancy has been suspected to harm the
      developing fetus. However, until now, no systematic analysis of the available
      evidence has been undertaken to assess the impact of maternal fever on health
      outcomes in the child. The goal of this study was to systematically review
      evidence from epidemiologic studies on adverse health outcomes of the offspring
      in relation to exposure to maternal fever during pregnancy. METHODS: Systematic
      searches in PubMed, Web of Science, and the Cochrane Library were performed by
      using Medical Subject Headings, Boolean operators, and truncation, and references
      of references were reviewed. Cohort and case-control studies addressing health
      outcomes of prenatal fever exposure in humans were eligible for inclusion.
      Studies with no direct reference to fever, studies in selected populations (eg,
      preterm births), and studies published before 1990 were excluded. RESULTS: The
      available literature supported an increased risk of adverse offspring health in
      association with fever during pregnancy. The strongest evidence was available for
      neural tube defects, congenital heart defects, and oral clefts, in which meta
      analyses suggested between a 1.5- and nearly 3-fold increased risk with fever
      exposure in the first trimester. We did not find strong evidence of a dose
      response relationship, but there was some evidence that antipyretic medications
      may have a protective effect when used in relation to febrile episodes.
      CONCLUSIONS: We found substantial evidence to support the contention that
      maternal fever during pregnancy may negatively affect offspring health. The
      harmful effects seemed to cover both short- and longer-term health outcomes;
      however, for several outcomes, the evidence was insufficient to judge any
      association.

PMID- 24567015
TI  - AAP principles concerning retail-based clinics.
AB  - The American Academy of Pediatrics views retail-based clinics (RBCs) as an
      inappropriate source of primary care for pediatric patients, as they fragment
      medical care and are detrimental to the medical home concept of longitudinal and
      coordinated care. This statement updates the original 2006 American Academy of
      Pediatrics statement on RBCs, which flatly opposed these sites as appropriate for
      pediatric care, discussing the shift in RBC focus and comparing attributes of
      RBCs with those of the pediatric medical home. 

PMID- 24567016
TI  - Psychosocial support for youth living with HIV.
AB  - This clinical report provides guidance for the pediatrician in addressing the
      psychosocial needs of adolescents and young adults living with HIV, which can
      improve linkage to care and adherence to life-saving antiretroviral (ARV)
      therapy. Recent national case surveillance data for youth (defined here as
      adolescents and young adults 13 to 24 years of age) revealed that the burden of
      HIV/AIDS fell most heavily and disproportionately on African American youth,
      particularly males having sex with males. To effectively increase linkage to care
      and sustain adherence to therapy, interventions should address the immediate
      drivers of ARV compliance and also address factors that provide broader social
      and structural support for HIV-infected adolescents and young adults.
      Interventions should address psychosocial development, including lack of future
      orientation, inadequate educational attainment and limited health literacy,
      failure to focus on the long-term consequences of near-term risk behaviors, and
      coping ability. Associated challenges are closely linked to the structural
      environment. Individual case management is essential to linkage to and retention
      in care, ARV adherence, and management of associated comorbidities. Integrating
      these skills into pediatric and adolescent HIV practice in a medical home setting
      is critical, given the alarming increase in new HIV infections in youth in the
      United States. 

PMID- 24567018
TI  - Arterial hypertension and posterior reversible cerebral edema syndrome induced by
      risperidone.
AB  - Posterior reversible cerebral edema syndrome is a generally reversible neurologic
      condition that is diagnosed based on distinctive clinical and radiologic
      findings. The condition, which is mostly associated with severe arterial
      hypertension, has also been reported to be induced by several medications. We
      made the diagnosis of hypertension with posterior reversible cerebral edema
      syndrome in a lean 12-year-old girl treated with the second-generation
      antipsychotic risperidone. We applied the Naranjo Adverse Drug Reaction
      Probability Scale and the World Health Organization-Uppsala Monitoring Centre
      system for causality assessment to the present case. Both scales indicated that a
      relationship to risperidone was likely. Second-generation antipsychotic agents
      may occasionally induce an increase in blood pressure even in the absence of
      overweight. Given this possibility, we recommend routine monitoring of blood
      pressure during therapy with these agents. 

PMID- 24567019
TI  - A health policy lesson learned, or not.

PMID- 24567017
TI  - Long-term outcomes of adolescents with juvenile-onset fibromyalgia in early
      adulthood.
AB  - OBJECTIVE: This prospective longitudinal study examined the long-term physical
      and psychosocial outcomes of adolescents with juvenile-onset fibromyalgia (JFM),
      compared with healthy control subjects, into early adulthood. METHODS: Adolescent
      patients with JFM initially seen at a pediatric rheumatology clinic (n = 94) and
      age- and gender-matched healthy control subjects (n = 33) completed online
      measures of demographic characteristics, pain, physical functioning, mood
      symptoms, and health care utilization at ~6 years' follow-up (mean age: 21
      years). A standard in-person tender-point examination was conducted. RESULTS:
      Patients with JFM had significantly higher pain (P < .001), poorer physical
      function (P < .001), greater anxiety (P < .001) and depressive symptoms (P <
      .001), and more medical visits (P < .001)than control subjects. The majority
      (>80%) of JFM patients continued to experience fibromyalgia symptoms into early
      adulthood, and 51.1% of the JFM sample met American College of Rheumatology
      criteria for adult fibromyalgia at follow-up. Patients with JFM were more likely
      than control subjects to be married and less likely to obtain a college
      education. CONCLUSIONS: Adolescent patients with JFM have a high likelihood of
      continued fibromyalgia symptoms into young adulthood. Those who met criteria for
      fibromyalgia in adulthood exhibited the highest levels of physical and emotional
      impairment. Emerging differences in educational attainment and marital status
      were also found in the JFM group. JFM is likely to be a long-term condition for
      many patients, and this study for the first time describes the wide-ranging
      impact of JFM on a variety of physical and psychosocial outcomes that seem to
      diverge from their same-age peers.

PMID- 24567020
TI  - Growth patterns of large for gestational age children up to age 4 years.
AB  - OBJECTIVE: To determine how growth of large for gestational age (LGA) preterm
      (PT) children was affected by their PT birth and their LGA status. METHODS: This
      is a community-based cohort study of 1302 PT and 489 full-term (FT) children,
      born 2002 and 2003. RESULTS: We found that growth in height, weight, and head
      circumference of LGA PT children was well balanced during infancy and that only
      weight gain accelerated during subsequent years. This led to high BMIs comparable
      to those of LGA FT children. Being born both LGA and PT resulted in a median
      growth at the age of 4 years that was 0.1 SD lower for weight (P = .44), 0.1 SD
      lower for height (P = .48), and 0.5 SD lower for head circumference compared with
      LGA FT counterparts (P = .016), whereas BMI at age 4 years was equal. Compared
      with appropriate for gestational age (AGA) PT children, these measures for LGA PT
      children were 0.9 SD, 0.6 SD, and 0.4 SD (all P < .001) higher, respectively.
      That led to the BMI of LGA PT children at age 4 years being significantly higher
      (0.9 points, i.e., 0.7 SD) than that of AGA PT and also higher (0.6 points, i.e.,
      0.4 SD) than that of AGA FT children. CONCLUSIONS: The growth patterns of LGA PT
      born children are distinctly different from other PT or FT children. In
      particular, we found substantially greater weight gains and relatively higher
      BMIs among them, which added to their already increased metabolic risks based on
      their gestational age.

PMID- 24567021
TI  - Use of electronic medical record-enhanced checklist and electronic dashboard to
      decrease CLABSIs.
AB  - OBJECTIVES: We hypothesized that a checklist enhanced by the electronic medical
      record and a unit-wide dashboard would improve compliance with an evidence-based,
      pediatric-specific catheter care bundle and decrease central line-associated
      bloodstream infections (CLABSI). METHODS: We performed a cohort study with
      historical controls that included all patients with a central venous catheter in
      a 24-bed PICU in an academic children's hospital. Postintervention CLABSI rates,
      compliance with bundle elements, and staff perceptions of communication were
      evaluated and compared with preintervention data. RESULTS: CLABSI rates decreased
      from 2.6 CLABSIs per 1000 line-days before intervention to 0.7 CLABSIs per 1000
      line-days after intervention. Analysis of specific bundle elements demonstrated
      increased daily documentation of line necessity from 30% to 73% (P < .001),
      increased compliance with dressing changes from 87% to 90% (P = .003), increased
      compliance with cap changes from 87% to 93% (P < .001), increased compliance with
      port needle changes from 69% to 95% (P < .001), but decreased compliance with
      insertion bundle documentation from 67% to 62% (P = .001). Changes in the care
      plan were made during review of the electronic medical record checklist on 39% of
      patient rounds episodes. CONCLUSIONS: Use of an electronic medical record
      enhanced CLABSI prevention checklist coupled with a unit-wide real-time display
      of adherence was associated with increased compliance with evidence-based
      catheter care and sustained decrease in CLABSI rates. These data underscore the
      potential for computerized interventions to promote compliance with proven best
      practices and prevent patient harm.

PMID- 24567022
TI  - Feasibility of critical congenital heart disease newborn screening at moderate
      altitude.
AB  - BACKGROUND AND OBJECTIVE: Consensus guidelines have recommended newborn pulse
      oximetry screening for critical congenital heart disease (CCHD). Given that
      newborn oxygen saturations are generally lower at higher altitudes, the American
      Academy of Pediatrics and others recommend additional evaluation of the screening
      algorithm at altitude. Our objective was to evaluate the feasibility of newborn
      pulse-oximetry CCHD screening at moderate altitude (Aurora, CO; 1694 m). We
      hypothesized the overall failure rate would be significantly higher compared with
      published controls. METHODS: We enrolled 1003 consecutive infants at >=35 weeks'
      gestation in a prospective observational study. The nationally recommended
      protocol for CCHD screening was adhered to with the exceptions of no reflex
      echocardiograms being performed and providers being informed of results only if
      saturations were less than predefined critical values. RESULTS: There were 1003
      infants enrolled, and 988 completed the screen. The overall failure rate for
      completed screenings was 1.1% (95% confidence interval: 0.6%-2.0%). The first 500
      infants had 1.6% fail, and the last 503 infants had 0.6% fail. Among infants who
      failed screening, 73% failed secondary to saturations <90%, whereas saturations
      between 90% and 94%, persistently >3% difference, and multiple criteria were each
      responsible for 9% of failures. Overall, 1.6% of all infants had incomplete
      screening and had not passed at the time the test was stopped. CONCLUSIONS: Pulse
      oximetry screening failure rates at moderate altitude are significantly higher
      than at sea level. Larger studies with alternative algorithms are warranted at
      moderate altitudes.

PMID- 24567023
TI  - Safety of medical interventions in children versus adults.
AB  - OBJECTIVE: Compare the risk of harm from pharmacologic interventions in pediatric
      versus adult randomized controlled trials (RCTs). METHODS: We used systematic
      reviews from the Cochrane Database of Systematic Reviews. We considered
      separately 7 categories of harms/harm-related end points: severe harms,
      withdrawals due to harms, any harm, organ system-level harms, specific harms,
      withdrawals for any reason, and mortality. Systematic reviews with quantitative
      synthesis from at least 1 adult and 1 pediatric RCT for any of those end points
      were eligible. We calculated the summary odds ratio (experimental versus control
      intervention) in adult and pediatric trials/meta-analysis; the relative odds
      ratio (ROR) in adults versus children per meta-analysis; and the summary ROR
      (sROR) across all meta-analyses for each end point. ROR <1 means that the
      experimental intervention fared worse in children than adults. RESULTS: We
      identified 176 meta-analyses for 52 types of harms/harm-related end points with
      669 adult and 184 pediatric RCTs. Of those, 165 had sufficient data for ROR
      estimation. sRORs showed statistically significant discrepancy between adults and
      children only for headache (sROR 0.82; 95% confidence interval 0.70-0.96).
      Nominally significant discrepancies for specific harms were identified in 12 of
      165 meta-analyses (RORs <1 in 7, ROR >1 in 5). In 36% of meta-analyses, the ROR
      estimates suggested twofold or greater differences between children and adults,
      and the 95% confidence intervals could exclude twofold differences only in 18% of
      meta-analyses. CONCLUSIONS: Available evidence on harms/harm-related end points
      from pharmacologic interventions has large uncertainty. Extrapolation of evidence
      from adults to children may be tenuous. Some clinically important discrepancies
      were identified.

PMID- 24567025
TI  - Meglitinide analogues in adolescent patients with HNF1A-MODY (MODY 3).
AB  - For pediatric patients with hepatocyte nuclear factor-1A (HNF1A)-maturity-onset
      diabetes of the young (MODY 3), treatment with sulfonylureas is recommended. In
      adults with HNF1A-MODY, meglitinide analogues achieve lower postprandial glucose
      levels and pose a lower risk of delayed hypoglycemia compared with sulfonylureas.
      This therapy has not yet been reviewed in pediatric patients. We report on
      meglitinide analogue treatment in 3 adolescents with HNF1A-MODY. Case 1 (14-year
      old girl) was diagnosed asymptomatically but had an hemoglobin A1c (HbA1c) level
      of 7.4%; her father had been recently diagnosed with HNF1A-MODY. With
      repaglinide, her HbA1c level decreased to 5.5%, with no hypoglycemic episodes.
      Case 2 (14-year-old boy) was diagnosed incidentally with glucosuria (HbA1c level:
      7.0%) and was treated with insulin. After the HNF1A-MODY diagnosis, he was
      switched to glibenclamide. Due to several hypoglycemic episodes, treatment was
      changed to nateglinide and his HbA1c level decreased to 6.2% with no further
      hypoglycemic episodes. Case 3 (11-year-old girl) presented with polyuria and
      polydipsia (HbA1c level: 10.1%) and was initially treated with insulin. After the
      HNF1A-MODY diagnosis, treatment was changed to repaglinide. She was obese (BMI:
      28.8 kg/m(2); z-score: +2.2), and glucose control with repaglinide alone was
      insufficient. Therefore, neutral protamine Hagedorn insulin (0.27 U/kg per day)
      was added. With this combination therapy, her HbA1c level decreased to 8.2%. The
      use of meglitinides in these 3 adolescent patients was well tolerated and
      effective. Furthermore, hypoglycemic episodes were rare compared with treatment
      with insulin or sulfonylureas. We therefore suggest considering meglitinides as
      the primary oral treatment option for adolescents suffering from HNF1A-MODY. 

PMID- 24567024
TI  - Variation in congenital heart surgery costs across hospitals.
AB  - BACKGROUND: A better understanding of costs associated with common and resource
      intense conditions such as congenital heart disease has become increasingly
      important as children's hospitals face growing pressure to both improve quality
      and reduce costs. We linked clinical information from a large registry with
      resource utilization data from an administrative data set to describe costs for
      common congenital cardiac operations and assess variation across hospitals.
      METHODS: Using linked data from The Society of Thoracic Surgeons and Pediatric
      Health Information Systems Databases (2006-2010), estimated costs/case for 9
      operations of varying complexity were calculated. Between-hospital variation in
      cost and associated factors were assessed by using Bayesian methods, adjusting
      for important patient characteristics. RESULTS: Of 12,718 operations (27
      hospitals) included, median cost/case increased with operation complexity (atrial
      septal defect repair, [$25,499] to Norwood operation, [$165,168]). Significant
      between-hospital variation (up to ninefold) in adjusted cost was observed across
      operations. Differences in length of stay (LOS) and complication rates explained
      an average of 28% of between-hospital cost variation. For the Norwood operation,
      high versus low cost hospitals had an average LOS of 50.8 vs. 31.8 days and a
      major complication rate of 50% vs. 25.3%. High volume hospitals had lower costs
      for the most complex operations. CONCLUSIONS: This study establishes benchmarks
      for hospital costs for common congenital heart operations and demonstrates wide
      variability across hospitals related in part to differences in LOS and
      complication rates. These data may be useful in designing initiatives aimed at
      both improving quality of care and reducing cost.

PMID- 24567026
TI  - Emergency contraception: addendum.

PMID- 24567027
TI  - Clinical utility of PCR for common viruses in acute respiratory illness.
AB  - BACKGROUND: Acute respiratory illness (ARI) accounts for a large proportion of
      all visits to pediatric health facilities. Quantitative real-time polymerase
      chain reaction (qPCR) analyses allow sensitive detection of viral nucleic acids,
      but it is not clear to what extent specific viruses contribute to disease because
      many viruses have been detected in asymptomatic children. Better understanding of
      how to interpret viral findings is important to reduce unnecessary use of
      antibiotics. OBJECTIVE: To compare viral qPCR findings from children with ARI
      versus asymptomatic control subjects. METHODS: Nasopharyngeal aspirates were
      collected from children aged <=5 years with ARI and from individually matched,
      asymptomatic, population-based control subjects during a noninfluenza season.
      Samples were analyzed by using qPCR for 16 viruses. RESULTS: Respiratory viruses
      were detected in 72.3% of the case patients (n = 151) and 35.4% of the control
      subjects (n = 74) (P = .001). Rhinovirus was the most common finding in both case
      patients and control subjects (47.9% and 21.5%, respectively), with a population
      attributable proportion of 0.39 (95% confidence interval: 0.01 to 0.62).
      Metapneumovirus, parainfluenza viruses, and respiratory syncytial virus were
      highly overrepresented in case patients. Bocavirus was associated with ARI even
      after adjustment for coinfections with other viruses and was associated with
      severe disease. Enterovirus and coronavirus were equally common in case patients
      and control subjects. CONCLUSIONS: qPCR detection of respiratory syncytial virus,
      metapneumovirus, or parainfluenza viruses in children with ARI is likely to be
      causative of disease; detection of several other respiratory viruses must be
      interpreted with caution due to high detection rates in asymptomatic children.

PMID- 24567028
TI  - Rehabilitation for improving automobile driving after stroke.
AB  - BACKGROUND: Interventions to improve driving ability after stroke, including
      driving simulation and retraining visual skills, have limited evaluation of their
      effectiveness to guide policy and practice. OBJECTIVES: To determine whether any
      intervention, with the specific aim of maximising driving skills, improves the
      driving performance of people after stroke. SEARCH METHODS: We searched the
      Cochrane Stroke Group Trials register (August 2013), the Cochrane Central
      Register of Controlled Trials (The Cochrane Library 2012, Issue 3), MEDLINE (1950
      to October 2013), EMBASE (1980 to October 2013), and six additional databases. To
      identify further published, unpublished and ongoing trials, we handsearched
      relevant journals and conference proceedings, searched trials and research
      registers, checked reference lists and contacted key researchers in the area.
      SELECTION CRITERIA: Randomised controlled trials (RCTs), quasi-randomised trials
      and cluster studies of rehabilitation interventions, with the specific aim of
      maximising driving skills or with an outcome of assessing driving skills in
      adults after stroke. The primary outcome of interest was the performance in an on
      road assessment after training. SECONDARY OUTCOMES included assessments of
      vision, cognition and driving behaviour. DATA COLLECTION AND ANALYSIS: Two review
      authors independently selected trials based on pre-defined inclusion criteria,
      extracted the data and assessed risk of bias. A third review author moderated
      disagreements as required. The review authors contacted all investigators to
      obtain missing information. MAIN RESULTS: We included four trials involving 245
      participants in the review. Study sample sizes were generally small, and
      interventions, controls and outcome measures varied, and thus it was
      inappropriate to pool studies. Included studies were at a low risk of bias for
      the majority of domains, with a high/unclear risk of bias identified in the areas
      of: performance (participants not blinded to allocation), and attrition
      (incomplete outcome data due to withdrawal) bias. Intervention approaches
      included the contextual approach of driving simulation and underlying skill
      development approach, including the retraining of speed of visual processing and
      visual motor skills. The studies were conducted with people who were relatively
      young and the timing after stroke was varied. PRIMARY OUTCOME: there was no clear
      evidence of improved on-road scores immediately after training in any of the four
      studies, or at six months (mean difference 15 points on the Test Ride for
      Investigating Practical Fitness to Drive - Belgian version, 95% confidence
      intervals (CI) 4.56 to 34.56, P value = 0.15, one study, 83 participants).
      SECONDARY OUTCOMES: road sign recognition was better in people who underwent
      training compared with control (mean difference 1.69 points on the Road Sign
      Recognition Task of the Stroke Driver Screening Assessment, 95% CI 0.51 to 2.87,
      P value = 0.007, one study, 73 participants). Significant findings were in favour
      of a simulator-based driving rehabilitation programme (based on one study with 73
      participants) but these results should be interpreted with caution as they were
      based on a single study. Adverse effects were not reported. There was
      insufficient evidence to draw conclusions on the effects on vision, other
      measures of cognition, motor and functional activities, and driving behaviour
      with the intervention. AUTHORS' CONCLUSIONS: There was insufficient evidence to
      reach conclusions about the use of rehabilitation to improve on-road driving
      skills after stroke. We found limited evidence that the use of a driving
      simulator may be beneficial in improving visuocognitive abilities, such as road
      sign recognition that are related to driving. Moreover, we were unable to find
      any RCTs that evaluated on-road driving lessons as an intervention. At present,
      it is unclear which impairments that influence driving ability after stroke are
      amenable to rehabilitation, and whether the contextual or remedial approaches, or
      a combination of both, are more efficacious.

PMID- 24567029
TI  - Differential transcriptional regulation of L-ascorbic acid content in peel and
      pulp of citrus fruits during development and maturation.
AB  - Citrus fruits are an important source of ascorbic acid (AsA) for human nutrition,
      but the main pathways involved in its biosynthesis and their regulation are still
      not fully characterized. To study the transcriptional regulation of AsA
      accumulation, expression levels of 13 genes involved in AsA biosynthesis, 5 in
      recycling and 5 in degradation were analyzed in peel and pulp of fruit of two
      varieties with different AsA concentration: Navel orange (Citrus sinensis) and
      Satsuma mandarin (Citrus unshiu). AsA accumulation in peel and pulp correlated
      with the transcriptional profiling of the L-galactose pathway genes, and the myo
      inositol pathway appeared to be also relevant in the peel of immature-green
      orange. Differences in AsA content between varieties were associated with
      differential gene expression of GDP-mannose pyrophosphorylase (GMP), GDP-L
      galactose phosphorylase (GGP) and L-galactose-1-phosphate phosphatase (GPP), myo
      inositol oxygenase in peel, and GGP and GPP in pulp. Relative expressions of
      monodehydroascorbate reductase 3 (MDHAR3) and dehydroascorbate reductase1 (DHAR1)
      correlated with AsA accumulation during development and ripening in peel and
      pulp, respectively, and were more highly expressed in the variety with higher AsA
      contents. Collectively, results indicated a differential regulation of AsA
      concentration in peel and pulp of citrus fruits that may change during the
      different stages of fruit development. The L-galactose pathway appears to be
      predominant in both tissues, but AsA concentration is regulated by complex
      mechanisms in which degradation and recycling also play important roles. 

PMID- 24567032
TI  - The University of Hawaii/University of Indonesia collaboration to build and
      sustain a child psychiatric workforce.
AB  - The authors describe the University of Hawaii/University of Indonesia
      collaboration, which introduced the specialty of child psychiatry to Indonesia in
      the early 1970s via a specially designed program, based in Hawaii, for five
      jointly selected Indonesian psychiatrists. All five graduates remained in
      Indonesia to practice and establish their own training program, which has since
      trained all of the "newer generation," such that there are currently 40 child and
      adolescent psychiatrists in Indonesia. Since 2009, collaboration between the two
      institutions has been renewed and modernized through videoteleconferencing,
      jointly conducted with teaching sessions. The authors present this program as an
      example of a collaboration that developed the local workforce and that has
      utilized modern technology in international, bidirectionally beneficial
      education. 

PMID- 24567031
TI  - Relationship-specific condom attitudes predict condom use among STD clinic
      patients with both primary and non-primary partners.
AB  - Although condom use differs by partner type (i.e., primary vs. non-primary
      partner), attitudes towards condom use are typically measured without
      consideration of partner type. This study investigated the predictive utility of
      condom attitudes measured separately by partner type. Participants were 270
      patients (37 % women, 72 % Black) recruited from a publicly-funded STD clinic who
      reported having both primary and non-primary partners. They completed a
      computerized survey assessing relationship-specific condom attitudes by partner
      type, condom attitudes related to pleasure and respect, and condom use with
      primary and non-primary partners. Participants reported more positive
      relationship-specific condom attitudes with a non-primary versus primary partner.
      When considering pleasure-related, respect-related, and relationship-specific
      condom attitudes simultaneously, only relationship-specific condom attitudes
      predicted unprotected sex, with both primary and non-primary partners. In
      general, pleasure and respect-related condom attitudes did not predict
      unprotected sex; however, pleasure-related attitudes predicted unprotected sex
      with a non-primary partner for men. Future research should assess relationship
      specific condom attitudes. Sexual risk reduction interventions that address
      interpersonal consequences of condom use in both primary and non-primary
      relationships should be a priority.

PMID- 24567033
TI  - Transforming neuroscience education in psychiatry.

PMID- 24567030
TI  - Regional brain distribution of translocator protein using [(11)C]DPA-713 PET in
      individuals infected with HIV.
AB  - Imaging the brain distribution of translocator protein (TSPO), a putative
      biomarker for glial cell activation and neuroinflammation, may inform management
      of individuals infected with HIV by uncovering regional abnormalities related to
      neurocognitive deficits and enable non-invasive therapeutic monitoring. Using the
      second-generation TSPO-targeted radiotracer, [(11)C]DPA-713, we conducted a
      positron emission tomography (PET) study to compare the brains of 12 healthy
      human subjects to those of 23 individuals with HIV who were effectively treated
      with combination antiretroviral therapy (cART). Compared to PET data from age
      matched healthy control subjects, [(11)C]DPA-713 PET of individuals infected with
      HIV demonstrated significantly higher volume-of-distribution (VT) ratios in white
      matter, cingulate cortex, and supramarginal gyrus, relative to overall gray
      matter VT, suggesting localized glial cell activation in susceptible regions.
      Regional TSPO abnormalities were evident within a sub-cohort of neuro
      asymptomatic HIV subjects, and an increase in the VT ratio within frontal cortex
      was specifically linked to individuals affected with HIV-associated dementia.
      These findings were enabled by employing a gray matter normalization approach for
      PET data quantification, which improved test-retest reproducibility, intra-class
      correlation within the healthy control cohort, and sensitivity of uncovering
      abnormal regional findings. 

PMID- 24567035
TI  - Toll-like receptor 2 promotes bacterial clearance during the initial stage of
      pulmonary infection with Acinetobacter baumannii.
AB  - Toll-like receptor 2 (TLR2) has been identified as a sensor for bacterial
      lipoprotein. To determine the role of TLR2 in host defense against Acinetobacter
      baumannii infection, wild-type (WT) and TLR2-deficient mice were infected
      intranasally with A. baumannii. Body weight, cytokine and chemokine levels in
      bronchoalveolar (BAL) fluid and lung histopathology were examined. Body weight
      changes in TLR2-deficient mice were comparable to those of WT mice throughout the
      experimental period. However, TLR2-deficient mice exhibited an increased
      bacterial load in the lungs and increased levels of interleukin-6 and chemokine
      (C-X-C motif) ligand 2 in BAL fluids compared with WT mice 1 day after infection.
      Histopathological features of lung tissue in WT and TLR2-deficient mice were
      comparable between WT and TLR2-deficient mice. Results of the present study
      demonstrate that TLR2 may have a minimal role in the host defense against A.
      baumannii at the early stages of infection.

PMID- 24567037
TI  - Non-assisted versus neuro-navigated and XperCT-guided external ventricular
      catheter placement: a comparative cadaver study.
AB  - BACKGROUND AND PURPOSE: Accurate placement of an external ventricular drain (EVD)
      for the treatment of hydrocephalus is of paramount importance for its
      functionality and in order to minimize morbidity and complications. The aim of
      this study was to compare two different drain insertion assistance tools with the
      traditional free-hand anatomical landmark method, and to measure efficacy, safety
      and precision. METHODS: Ten cadaver heads were prepared by opening large bone
      windows centered on Kocher's points on both sides. Nineteen physicians, divided
      in two groups (trainees and board certified neurosurgeons) performed EVD
      insertions. The target for the ventricular drain tip was the ipsilateral foramen
      of Monro. Each participant inserted the external ventricular catheter in three
      different ways: 1) free-hand by anatomical landmarks, 2) neuronavigation-assisted
      (NN), and 3) XperCT-guided (XCT). The number of ventricular hits and dangerous
      trajectories; time to proceed; radiation exposure of patients and physicians;
      distance of the catheter tip to target and size of deviations projected in the
      orthogonal plans were measured and compared. RESULTS: Insertion using XCT
      increased the probability of ventricular puncture from 69.2 to 90.2 % (p = 0.02).
      Non-assisted placements were significantly less precise (catheter tip to target
      distance 14.3 +/- 7.4 mm versus 9.6 +/- 7.2 mm, p = 0.0003). The insertion time
      to proceed increased from 3.04 +/- 2.06 min. to 7.3 +/- 3.6 min. (p < 0.001). The
      X-ray exposure for XCT was 32.23 mSv, but could be reduced to 13.9 mSv if
      patients were initially imaged in the hybrid-operating suite. No supplementary
      radiation exposure is needed for NN if patients are imaged according to a
      navigation protocol initially. CONCLUSION: This ex vivo study demonstrates a
      significantly improved accuracy and safety using either NN or XCT-assisted
      methods. Therefore, efforts should be undertaken to implement these new
      technologies into daily clinical practice. However, the accuracy versus urgency
      of an EVD placement has to be balanced, as the image-guided insertion technique
      will implicate a longer preparation time due to a specific image acquisition and
      trajectory planning.

PMID- 24567036
TI  - Antihypertensive medications and serious fall injuries in a nationally
      representative sample of older adults.
AB  - IMPORTANCE The effect of serious injuries, such as hip fracture and head injury,
      on mortality and function is comparable to that of cardiovascular events.
      Concerns have been raised about the risk of fall injuries in older adults taking
      antihypertensive medications. The low risk of fall injuries reported in clinical
      trials of healthy older adults may not reflect the risk in older adults with
      multiple chronic conditions. OBJECTIVE To determine whether antihypertensive
      medication use was associated with experiencing a serious fall injury in a
      nationally representative sample of older adults. DESIGN, PARTICIPANTS, AND
      SETTING Competing risk analysis as performed with propensity score adjustment and
      matching in the nationally representative Medicare Current Beneficiary Survey
      cohort during a 3-year follow-up through 2009. Participants included 4961
      community-living adults older than 70 years with hypertension. EXPOSURES
      Antihypertensive medication intensity based on the standardized daily dose for
      each antihypertensive medication class that participants used. MAIN OUTCOMES AND
      MEASURES Serious fall injuries, including hip and other major fractures,
      traumatic brain injuries, and joint dislocations, ascertained through Centers for
      Medicare & Medicaid Services claims. RESULTS Of the 4961 participants, 14.1%
      received no antihypertensive medications; 54.6% were in the moderate-intensity
      and 31.3% in the high-intensity antihypertensive groups. During follow-up, 446
      participants (9.0%) experienced serious fall injuries, and 837 (16.9%) died. The
      adjusted hazard ratios for serious fall injury were 1.40 (95% CI, 1.03-1.90) in
      the moderate-intensity and 1.28 (95% CI, 0.91-1.80) in the high-intensity
      antihypertensive groups compared with nonusers. Although the difference in
      adjusted hazard ratios across the groups did not reach statistical significance,
      results were similar in the propensity score-matched subcohort. Among 503
      participants with a previous fall injury, the adjusted hazard ratios were 2.17
      (95% CI, 0.98-4.80) for the moderate-intensity and 2.31 (95% CI, 1.01-5.29) for
      the high-intensity antihypertensive groups. CONCLUSIONS AND RELEVANCE
      Antihypertensive medications were associated with an increased risk of serious
      fall injuries, particularly among those with previous fall injuries. The
      potential harms vs benefits of antihypertensive medications should be weighed in
      deciding to continue treatment with antihypertensive medications in older adults
      with multiple chronic conditions. 

PMID- 24567039
TI  - Planar Mobius aromatic pentalenes incorporating 16 and 18 valence electron
      osmiums.
AB  - Aromaticity, a highly stabilizing feature of molecules with delocalized electrons
      in closed circuits, is generally restricted to 'Huckel' systems with 4n+2 mobile
      electrons. Although the Mobius concept extends the principle of aromaticity to 4n
      mobile electron species, the rare known examples have complex, twisted topologies
      whose extension is unlikely. Here we report the realization of osmapentalenes,
      the first planar Mobius aromatic complexes with 16 and 18 valence electron
      transition metals. The Mobius aromaticity of these osmapentalenes, documented by
      X-ray structural, magnetic and theoretical analyses, demonstrates the basis of
      the aromaticity of the parent osmapentalynes. All these osmapentalenes are formed
      by both electrophilic and nucleophilic reactions of the in-plane pi component of
      the same carbyne carbon, illustrating ambiphilic carbyne reactivity, which is
      seldom observed in transition metal chemistry. Our results widen the scope of
      Mobius aromaticity dramatically and open prospects for the generalization of
      planar Mobius aromatic chemistry. 

PMID- 24567040
TI  - Unfolding a design rule for microparticle buffering and dropping in microring
      resonator-based add-drop devices.
AB  - We propose an intuitive and quantitative design rule to determine the
      microparticle transport processes, including buffering and dropping, on microring
      resonator-based add-drop devices at cavity resonances in an integrated
      optofluidic chip. The design rule uses the splitting ratio, S, of the optical
      field intensity at the microring feedback-arc just after the output-coupling
      region to that at the drop-waveguide as a figure-of-merit for particle transport
      to determine between particle buffering (S > 1) and dropping (S < 1). The
      particle transport, however, becomes probabilistic in the case that S is close to
      1. The S factor thus provides a clearer physical criterion for determining the
      particle transport processes compared to the cavity quality (Q) factor. We
      experimentally investigate this design rule on four different devices with
      different design parameters on a silicon nitride-on-silica substrate, and show
      that the particle transport behaviours of 2.2 MUm- and 0.8 MUm-sized polystyrene
      particles are consistent with the S values extracted from the transmission
      spectra. Our numerical simulations of the four devices suggest that the S values
      extracted from the simulated transmission spectra are consistent with those
      extracted from the simulated mode-field intensity distributions. We calculate the
      optical force field using Maxwell stress tensor and an effective microdisk model
      to relate the S values to the particle transport processes. We further
      experimentally demonstrate the viability of the design rule by switching between
      deterministic particle buffering and probabilistic particle transport processes
      by switching the polarization modes. 

PMID- 24567038
TI  - Repeated cocaine treatment enhances HIV-1 Tat-induced cortical excitability via
      over-activation of L-type calcium channels.
AB  - The prefrontal cortex (PFC) is dysregulated in neuroAIDS and during cocaine
      abuse. Repeated cocaine treatment upregulates voltage gated L-type Ca(2+)
      channels in pyramidal neurons within the rat medial PFC (mPFC). L-type Ca(2+)
      channels are also upregulated by the HIV-1 neurotoxic protein, Tat, but the role
      of Tat in pyramidal cell function is unknown. This represents a major knowledge
      gap as PFC pyramidal neurons are important mediators of behaviors that are
      disrupted in neuroAIDS and by chronic cocaine exposure. To determine if L-channel
      mediated Ca(2+) dysregulation in mPFC pyramidal neurons are a common
      neuropathogenic site for Tat and chronic cocaine, we evaluated the
      electrophysiological effects of recombinant Tat on these neurons in forebrain
      slices taken from rats 1-3 days after five, once-daily treatments of cocaine (15
      mg/kg, ip) or saline. In saline-treated rats, bath-applied Tat facilitated
      membrane depolarization and firing. Ca(2+) influx was increased (indicated by
      prolonged Ca(2+) spikes) with low concentrations of Tat (10-40nM), but reduced by
      higher concentrations (80-160nM), the latter likely reflecting dysfunction
      associated with excessive excitation. Tat-mediated effects were detected during
      NMDA/AMPA receptor blockade, and abolished by blocking activated L-channels with
      diltiazem. In neurons from cocaine-treated rats, the Tat-induced effects on
      evoked firing and Ca(2+) spikes were significantly enhanced above that obtained
      with Tat in slices from saline-treated rats. Thus, glutamatergic receptor
      independent over-activation of L-channels contributed to the Tat-induced hyper
      reactivity of mPFC pyramidal neurons to excitatory stimuli, which was exacerbated
      in rats repeatedly exposed to cocaine. Such effects may contribute to the
      exaggerated neuropathology reported for HIV(+) cocaine-abusing individuals. 

PMID- 24567041
TI  - Environmental contamination, product contamination and workers exposure using a
      robotic system for antineoplastic drug preparation.
AB  - Environmental contamination, product contamination and technicians exposure were
      measured following preparation of iv bags with cyclophosphamide using the robotic
      system CytoCare. Wipe samples were taken inside CytoCare, in the clean room
      environment, from vials, and prepared iv bags including ports and analysed for
      contamination with cyclophosphamide. Contamination with cyclophosphamide was also
      measured in environmental air and on the technicians hands and gloves used for
      handling the drugs. Exposure of the technicians to cyclophosphamide was measured
      by analysis of cyclophosphamide in urine. Contamination with cyclophosphamide was
      mainly observed inside CytoCare, before preparation, after preparation and after
      daily routine cleaning. Contamination outside CytoCare was incidentally found.
      All vials with reconstituted cyclophosphamide entering CytoCare were contaminated
      on the outside but vials with powdered cyclophosphamide were not contaminated on
      the outside. Contaminated bags entering CytoCare were also contaminated after
      preparation but non-contaminated bags were not contaminated after preparation.
      Cyclophosphamide was detected on the ports of all prepared bags. Almost all outer
      pairs of gloves used for preparation and daily routine cleaning were contaminated
      with cyclophosphamide. Cyclophosphamide was not found on the inner pairs of
      gloves and on the hands of the technicians. Cyclophosphamide was not detected in
      the stationary and personal air samples and in the urine samples of the
      technicians. CytoCare enables the preparation of cyclophosphamide with low levels
      of environmental contamination and product contamination and no measurable
      exposure of the technicians. 

PMID- 24567042
TI  - The surgeon's limited responsibility in the operating room.

PMID- 24567043
TI  - Commentaries on data published by Riggio et al. and discussion by Otterburn on
      locoregional risk following mastectomy after lipofilling.

PMID- 24567044
TI  - An aesthetic approach to the anterior cranial fossa: the endoscopic transadnexal
      transorbital roof method.
AB  - BACKGROUND: This case report describes a transadnexal transorbital roof approach
      to the anterior cranial fossa to treat an epidural abscess in a patient who had
      previously undergone extensive craniofacial reconstruction secondary to fibrous
      dysplasia. A standard frontal craniotomy or even a supraciliary craniotomy would
      have been burdensome due to the positioning of the porous polyethylene implant as
      well as extensive scar tissue and adhesions from prior surgical procedures.
      METHODS: We performed a retrospective review of the case of a 15-year-old male
      with an epidural abscess treated at a university hospital. RESULTS: The patient
      tolerated the procedure well with no postoperative complications. Surgical
      operative time was approximately 1.5 h with minimal blood loss and the patient
      was discharged on postoperative day 2. Six weeks after antibiotic therapy
      (intravenous ampicillin/sulbactam, 2,000 mg q.i.d. for 6 days total), an MRI
      showed complete resolution of the epidural abscess. At that time the patient had
      no visual changes, extraocular muscle dysfunction, headaches, periorbital
      cellulitis, or further seizures and is on no antiepileptic therapy. CONCLUSION:
      Minimally invasive approaches to treat complex problems in certain circumstances
      can yield excellent results and limit morbidity encountered by more extensive
      procedures. In the future, more formal studies with a larger subset of patients
      will help determine what role these approaches will ultimately have. 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- 24567045
TI  - Use of transcutaneous ultrasound for lipolysis and skin tightening: a review.
AB  - Several ultrasonic devices have recently been investigated for their ability to
      decrease areas of focal adiposity and tighten small areas of the skin. Studies
      show that ultrasound technology offers a safe, reliable, and predictable means to
      sculpt the body of nonobese patients, but its efficacy remains uncertain.
      Although most studies claim statistically significant results, the clinical
      significance of ultrasound technology has yet to be determined. Most studies use
      waist circumference measurements to determine statistical significance and
      efficacy. The majority of the current studies also have a relatively a short
      follow-up period of 3 months. More studies are needed to assess the true efficacy
      of ultrasound technology using more reliable measurements such as diagnostic
      ultrasound and computed tomography (CT) imaging and to include a follow-up period
      longer than 6 months to obtain more valid results. LEVEL OF EVIDENCE III: This
      journal requires that authors assign a level of evidence to each article. For a
      full description of these Evidence-Based Medicine ratings, please refer to the
      Table of Contents or the online Instructions to Authors www.springer.com/00266 .

PMID- 24567046
TI  - Circadian release of male-specific components of the greater date moth, Aphomia
      (Arenipses) sabella, using sequential SPME/GC/MS analysis.
AB  - The greater date moth (GDM), Aphomia sabella Hampson (Lepidoptera: Pyralidae:
      Galleriinae), is a serious pest of date palms, Phoenix dactylifera. The release
      of volatiles from both males and females was investigated using sequential
      SPME/GC/MS analysis. Males release a complex mixture of compounds in a circadian
      rhythm during the night between 03:00 and 05:00 hr. Six compounds were
      identified: benzaldehyde, sulcatol (6-methyl-5-hepten-2-ol), geranyl acetone [(E)
      6,10-dimethyl-5,9-undecadien-2-one], phenylacetaldehyde, 2-phenylpropenal, and
      (R)-fuscumol [(R)-(E)-6, 10-dimethyl-5, 9-undecadien-2-ol]. Benzaldehyde,
      sulcatol, and geranyl acetone were found only in trace amounts. These compounds
      were in glands located in the forewing of males only. Small amounts of acetoin
      and 2,3-butanediol were found sporadically in the SPME/GC/MS analyses of
      volatiles from females, and these compounds probably originate from
      microorganisms. This is the first finding of a circadian release of male-specific
      compounds in moths. GC/EAD analyses with synthetic standards of compounds
      released by males showed that the female antenna is stimulated by all six
      compounds, while the male antenna responded only to phenylacetaldehyde. A
      possible pheromonal role for the male-specific compounds is suggested by the
      circadian rhythm of their release and the EAD response of females to them.
      However, trapping tests with the main male-specific compounds in screen cages in
      the laboratory or in the field did not reveal any significant behavioral
      responses from females or males. Copulation in the laboratory was observed only
      in the presence of date palm tissue, thus suggesting that sexual communication
      and mating of GDM moths probably occurs in the crown of date palms.

PMID- 24567048
TI  - Assessing attachment in the school years: the application of the Dynamic
      Maturational Model of Attachment to the coding of a child attachment interview
      with community and looked-after children.
AB  - BACKGROUND: This article reports on the analysis of a Child Attachment Interview
      using the Dynamic Maturational Model (DMM) of attachment coding system developed
      by Crittenden for use with the Adult Attachment Interview (AAI). The aim of the
      study was to see if the two coders could classify the child interviews using the
      DMM-AAI approach and produce the range of DMM attachment strategies to be
      expected from previous research and the literature. METHODS: Two coders
      independently classified interviews with 41 children aged between 6 and 13 years
      with an average age of 9.8 years. In total, 24 of the children were from a local
      authority middle school (the community children) and 17 were in foster care
      (looked-after children). RESULTS: The full array of DMM strategies was
      identified, with significant differences between the community and looked-after
      children in terms of attachment security and lack of resolution of loss and
      trauma. There was 100% agreement between coders on secure versus insecure
      attachment patterns, a Kappa of .910 for the full range of DMM attachment
      strategies and Kappas of between .655 and .773 for unresolved loss, trauma and
      depression. Discussion focuses on the strengths and deficits of the use of the
      DMM compared with other published work on child attachment interviews, the use of
      interviews to assess post-traumatic stress disorder in children and the
      implications of defensive attachment strategies for services offered to looked
      after children.

PMID- 24567047
TI  - Bayesian QTL analyses using pedigreed families of an outcrossing species, with
      application to fruit firmness in apple.
AB  - KEY MESSAGE: Proof of concept of Bayesian integrated QTL analyses across pedigree
      related families from breeding programs of an outbreeding species. Results
      include QTL confidence intervals, individuals' genotype probabilities and genomic
      breeding values. Bayesian QTL linkage mapping approaches offer the flexibility to
      study multiple full sib families with known pedigrees simultaneously. Such a
      joint analysis increases the probability of detecting these quantitative trait
      loci (QTL) and provide insight of the magnitude of QTL across different genetic
      backgrounds. Here, we present an improved Bayesian multi-QTL pedigree-based
      approach on an outcrossing species using progenies with different (complex)
      genetic relationships. Different modeling assumptions were studied in the QTL
      analyses, i.e., the a priori expected number of QTL varied and polygenic effects
      were considered. The inferences include number of QTL, additive QTL effect sizes
      and supporting credible intervals, posterior probabilities of QTL genotypes for
      all individuals in the dataset, and QTL-based as well as genome-wide breeding
      values. All these features have been implemented in the FlexQTL(TM) software. We
      analyzed fruit firmness in a large apple dataset that comprised 1,347 individuals
      forming 27 full sib families and their known ancestral pedigrees, with genotypes
      for 87 SSR markers on 17 chromosomes. We report strong or positive evidence for
      14 QTL for fruit firmness on eight chromosomes, validating our approach as
      several of these QTL were reported previously, though dispersed over a series of
      studies based on single mapping populations. Interpretation of linked QTL was
      possible via individuals' QTL genotypes. The correlation between the genomic
      breeding values and phenotypes was on average 90 %, but varied with the number of
      detected QTL in a family. The detailed posterior knowledge on QTL of potential
      parents is critical for the efficiency of marker-assisted breeding.

PMID- 24567051
TI  - Evidence for external forcing of the Atlantic Multidecadal Oscillation since
      termination of the Little Ice Age.
AB  - The Atlantic Multidecadal Oscillation (AMO) represents a significant driver of
      Northern Hemisphere climate, but the forcing mechanisms pacing the AMO remain
      poorly understood. Here we use the available proxy records to investigate the
      influence of solar and volcanic forcing on the AMO over the last ~450 years. The
      evidence suggests that external forcing played a dominant role in pacing the AMO
      after termination of the Little Ice Age (LIA; ca. 1400-1800), with an
      instantaneous impact on mid-latitude sea-surface temperatures that spread across
      the North Atlantic over the ensuing ~5 years. In contrast, the role of external
      forcing was more ambiguous during the LIA. Our study further suggests that the
      Atlantic Meridional Overturning Circulation is important for linking external
      forcing with North Atlantic sea-surface temperatures, a conjecture that
      reconciles two opposing theories concerning the origin of the AMO. 

PMID- 24567049
TI  - Hyperthyroidism is a risk factor for developing adhesive capsulitis of the
      shoulder: a nationwide longitudinal population-based study.
AB  - The purpose of this study was to investigate the prevalence and risk of adhesive
      capsulitis among hyperthyroidism patients. The data were obtained from the
      Longitudinal Health Insurance Database 2005 (LHID 2005) in Taiwan, using 1
      million participants and a prospective population-based 7-year cohort study of
      survival analysis. The ambulatory-care claim records of patients diagnosed
      according to the International Classification of Diseases, Ninth Revision,
      Clinical Modification (ICD-9-CM) codes relating to hyperthyroidism between
      January 1, 2004 and December 31, 2007, were obtained. The prevalence and the
      adjusted hazard ratio (HR) of adhesive capsulitis among hyperthyroid patients and
      the control group were estimated. Of 4472 hyperthyroid patients, 162 (671/100,000
      person-years) experienced adhesive capsulitis during the 24,122 person-year
      follow-up period. The crude HR of stroke was 1.26 (95% confidence interval [CI],
      1.06 to 1.49), which was larger than that of the control group. The adjusted HR
      of developing adhesive capsulitis was 1.22 (95% CI, 1.03 to 1.45) for
      hyperthyroid patients during the 7-year follow-up period, which achieved
      statistical significance. The results of our large-scale longitudinal population
      based study indicated that hyperthyroidism is an independent risk factor of
      developing adhesive capsulitis.

PMID- 24567052
TI  - Community engagement as a process and an outcome of developing culturally
      grounded health communication interventions: an example from the DECIDE project.
AB  - Community engagement is a process often used in developing effective health
      communication interventions, especially in traditionally underserved cultural
      contexts. While the potentially positive outcomes of community engagement are
      well established, the communication processes that result in engagement with
      cultural groups are less apparent. The focus on the outcomes of engagement at the
      expense of describing how engagement occurs makes it difficult for methods to be
      improved upon and replicated by future studies. The purpose of the current
      manuscript is to illustrate the process of achieving community engagement through
      the development of a culturally grounded health communication intervention. We
      offer practical suggestions for implementing community engagement principles, as
      well as the benefits and challenges inherent in this approach to research. Key
      points are illustrated using examples from the DECIDE Project, a culturally
      grounded intervention for improving communication about clinical trials in the
      medically underserved Appalachian region. 

PMID- 24567053
TI  - Adherence compounds in embryo transfer media for assisted reproductive
      technologies.
AB  - BACKGROUND: This is an update of a Cochrane review first published in The
      Cochrane Library (2010, Issue 7).To increase the success rate of assisted
      reproductive technologies (ART), adherence compounds such as hyaluronic acid (HA)
      and fibrin sealant have been introduced into subfertility management. Adherence
      compounds are added to the embryo transfer medium to increase the likelihood of
      embryo implantation, with the potential for higher clinical pregnancy and live
      birth rates. OBJECTIVES: To determine whether embryo transfer media containing
      adherence compounds improved live birth and pregnancy rates in ART cycles. SEARCH
      METHODS: The Menstrual Disorders and Subfertility Group Trials Register, the
      Cochrane Central Register of Controlled Trials (CENTRAL) and MEDLINE, EMBASE and
      PsycINFO electronic databases were searched (up to 13 November 2013) to look for
      publications that described randomised controlled trials on the addition of
      adherence compounds to embryo transfer media. Furthermore, reference lists of all
      obtained studies were checked, and conference abstracts were handsearched.
      SELECTION CRITERIA: Only truly randomised controlled trials comparing embryo
      transfer media containing functional (e.g. 0.5 mg/ml HA) concentrations of
      adherence compounds versus transfer media containing low or no concentrations of
      adherence compounds were included. The adherence compounds that were identified
      for evaluation were HA and fibrin sealant. DATA COLLECTION AND ANALYSIS: Two
      review authors selected trials for inclusion according to the above criteria,
      after which two review authors independently extracted the data for subsequent
      analysis. Statistical analysis was performed in accordance with the guidelines
      developed by The Cochrane Collaboration. MAIN RESULTS: Seventeen studies with a
      total of 3898 participants were analysed. One studied fibrin sealant, and the
      other 16 studied HA. No evidence was found of a treatment effect of fibrin
      sealant as an adherence compound. For HA, evidence of a positive treatment effect
      was identified in the six trials that reported live birth rates (odds ratio (OR)
      1.41, 95% confidence interval (CI) 1.17 to 1.69; six RCTs, N = 1950, I(2) = 0%,
      moderate-quality evidence). Furthermore, the 14 trials reporting clinical
      pregnancy rates showed evidence of treatment benefit when embryos were
      transferred in media containing functional concentrations of HA (OR 1.39, 95% CI
      1.21 to 1.60; 14 RCTs, N = 3452, I(2) = 46%, moderate-quality evidence) as
      compared with low or no use of HA. The multiple pregnancy rate (OR 1.86, 95% CI
      1.49 to 2.31; five RCTs, N = 1951, I(2) = 0%, moderate-quality evidence) was
      significantly increased in the high HA group, but no significant differences in
      adverse event rates were found (OR 0.74, 95% CI 0.49 to 1.12; four RCTs, N =
      1525, I(2) = 0%, moderate-quality evidence). AUTHORS' CONCLUSIONS: Evidence
      suggests improved clinical pregnancy and live birth rates with the use of
      functional concentrations of HA as an adherence compound in ART cycles. However,
      the evidence obtained is of moderate quality. The increase in multiple pregnancy
      rate may be the result of use of a combination of an adherence compound and a
      policy of transferring more than one embryo. Further studies of adherence
      compounds with single embryo transfer need to be undertaken.

PMID- 24567055
TI  - Progesterone alters Nogo-A, GFAP and GAP-43 expression in a rat model of
      traumatic brain injury.
AB  - Previous studies have demonstrated that progesterone has neuroprotective effects
      in the central nervous system (CNS) following traumatic brain injury (TBI).
      Numerous cellular mechanisms have been reported to be important in the
      neuroprotective effects of progesterone, including the reduction of edema,
      inflammation and apoptosis, and the inhibition of oxidative stress. However, the
      effect of progesterone on neuronal protection following TBI remains unclear. The
      present study aimed to investigate the effects of progesterone on the expression
      of Nogo-A, an inhibitor of axonal growth, glial fibrillary acidic protein (GFAP),
      a main component of the glial scar and growth-associated protein-43 (GAP-43), a
      signaling molecule in neuronal growth in TBI rats. The TBI model was produced by
      the weight drop method. In total, 75 rats were assigned to three groups: the sham
      group, TBI group with vehicle treatment and TBI group with progesterone
      treatment. The protein expression of Nogo-A, GFAP and GAP-43 in the cortex and
      the hippocampus was examined by immunocytochemistry. TBI rats significantly
      increased the expression of Nogo-A, GFAP, and GAP-43 at 1, 3, 7 and 14 days post
      injury. Progesterone significantly decreased the expression of Nogo-A and GFAP,
      and upregulated the GAP-43 protein. Our findings suggested that progesterone
      promotes neuroprotection following TBI by inhibiting the expression of Nogo-A and
      GFAP, and increasing GAP-43 expression.

PMID- 24567058
TI  - Osteoarthritis: blocking cartilage damage in a rat model of OA by intra-articular
      injection of an amniotic membrane allograft.

PMID- 24567059
TI  - Osteoarthritis: circulating miRNAs-early osteoarthritis biomarkers?

PMID- 24567056
TI  - Polymorphisms of HIF1A gene are associated with prognosis of early stage non
      small-cell lung cancer patients after surgery.
AB  - Hypoxia-inducible factor 1alpha (HIF1alpha) activates the transcription of genes
      that are involved in angiogenesis and cell survival. Over-expression of HIF1alpha
      caused by intratumoral hypoxia and its genetic alterations are associated with
      increased mortality in several cancer types including non-small-cell lung cancer
      (NSCLC). The aim of this study was to investigate the predictive role of single
      nucleotide polymorphisms (SNPs) in HIF1A gene in NSCLC outcomes. We genotyped two
      functional SNPs (rs2057482 and rs2301113) in HIF1A gene and assessed their
      associations with clinicopathological parameters and prognosis of 494 NSCLC
      patients by Cox proportional hazard model. There was no significant association
      between the SNPs and clinical outcomes of NSCLC for overall analysis. However, in
      stratified analysis for NSCLC patients at early stage (I/II), we observed a
      protective effect conferred by variant genotype of rs2057482 on overall survival
      (OS) (HR 0.42, 95% CI 0.22-0.80) and recurrence-free survival (RFS) (HR 0.60, 95
      % CI 0.36-0.97) in a dominant model. Additionally, multivariate Cox analysis
      based on dominant model indicated that significant increased death and recurrence
      risks were observed in patients with early T-stage (T1 and T2) tumors, who
      carrying variant-containing genotype of rs2301113, as well as in patients without
      lymph node involvement (N0 stage) for rs2057482. Genetic variations on HIF1A gene
      are significantly associated with NSCLC outcomes in patients with early stage
      disease.

PMID- 24567057
TI  - Evaluation of histidine-rich glycoprotein tissue RNA and serum protein as novel
      markers for breast cancer.
AB  - Advances in the field of breast cancer (BC) biomarkers discovery facilitate
      diagnosis and treatment of BC in its pre-invasive state. While the genetic tissue
      markers are making significant advances in understanding the molecular basis of
      BC, serum has long been considered a rich source for biomarkers. So, integrated
      genomic and proteomic strategies play a huge role in the analytical validation of
      BC biomarkers and represent a true milestone in the areas of diagnostics and
      personalized medicine. This study included 60 cases (BC), 30 patients with
      fibroadenoma and 30 healthy women. Histidine-rich glycoprotein RNA (HRG) tissue
      expression was analyzed through gene expression-based outcome for breast cancer
      online algorithm (GOBO) bioinformatic analysis. To confirm our informatics
      analysis, HRG RNA was detected in breast tissue samples by RT-PCR, and HRG serum
      protein was estimated by ELISA. GOBO analysis revealed increased HRG RNA
      expression in all subtypes of BC with relative higher expression in basal subtype
      and grade 2. We confirmed these findings by HRG tissue RNA with 71.7% sensitivity
      and 93.3% specificity. HRG serum protein was 86.7% sensitivity and 80%
      specificity. HRG tissue RNA and serum protein could be considered as promising
      novel markers for prediction of BC prognosis.

PMID- 24567061
TI  - Genetics: a new interpretation of genetic studies in RA.
AB  - Understanding the genetics of rheumatoid arthritis (RA) is complex, multiple
      genes and environmental factors are involved. A new multicentre genetic study
      summarizes the fundamental gene polymorphisms, pathways and cell types that are
      related to RA and, based on this analysis, proposes new targets for RA drug
      treatments.

PMID- 24567066
TI  - Cu-mediated enamide formation in the total synthesis of complex peptide natural
      products.
AB  - Cu-mediated C(sp(2))-N bond formation has received intense interest recently, and
      has been applied to the total synthesis of a wide variety of structurally complex
      natural products. This review covers the synthetic assembly of peptide natural
      products in which Cu-mediated enamide formation is the key transformation. The
      total syntheses of cyclopeptide alkaloids, pacidamycin D, and yaku'amide A
      exemplify the versatility of the Cu-catalyzed cross-coupling reaction in
      comparison to other synthetic methods.

PMID- 24567054
TI  - Prenatal antidepressant exposure: clinical and preclinical findings.
AB  - Pharmacological treatment of any maternal illness during pregnancy warrants
      consideration of the consequences of the illness and/or medication for both the
      mother and unborn child. In the case of major depressive disorder, which affects
      up to 10-20% of pregnant women, the deleterious effects of untreated depression
      on the offspring can be profound and long lasting. Progress has been made in our
      understanding of the mechanism(s) of action of antidepressants, fetal exposure to
      these medications, and serotonin's role in development. New technologies and
      careful study designs have enabled the accurate sampling of maternal serum,
      breast milk, umbilical cord serum, and infant serum psychotropic medication
      concentrations to characterize the magnitude of placental transfer and exposure
      through human breast milk. Despite this progress, the extant clinical literature
      is largely composed of case series, population-based patient registry data that
      are reliant on nonobjective means and retrospective recall to determine both
      medication and maternal depression exposure, and limited inclusion of suitable
      control groups for maternal depression. Conclusions drawn from such studies often
      fail to incorporate embryology/neurotransmitter ontogeny, appropriate gestational
      windows, or a critical discussion of statistically versus clinically significant.
      Similarly, preclinical studies have predominantly relied on dosing models,
      leading to exposures that may not be clinically relevant. The elucidation of a
      defined teratological effect or mechanism, if any, has yet to be conclusively
      demonstrated. The extant literature indicates that, in many cases, the benefits
      of antidepressant use during pregnancy for a depressed pregnant woman may
      outweigh potential risks. 

PMID- 24567065
TI  - Pain and the context.
AB  - Pain is a sensory and emotional experience that is substantially modulated by
      psychological, social and contextual factors. Research now indicates that the
      influence of these factors is even more powerful than expected and involves the
      therapeutic response to analgesic drugs as well as the pain experience itself,
      which in some circumstances can even be a form of reward. Different experimental
      approaches and models, both in the laboratory and in the clinical setting, have
      been used to better characterize and understand the complex neurobiology of pain
      modulation. These approaches include placebo analgesia, nocebo hyperalgesia,
      hidden administration of analgesics, and the manipulation of the pain-reward
      relationship. Overall, these studies show that different neurochemical systems
      are activated in different positive and negative contexts. Moreover, pain can
      activate reward mechanisms when experienced within contexts that have special
      positive meaning. Because routine medical practice usually takes place in
      contexts that use different rituals, these neurobiological insights might have
      profound clinical implications.

PMID- 24567067
TI  - Investigating the role of transferrin in the distribution of iron, manganese,
      copper, and zinc.
AB  - The essential role of transferrin in mammalian iron metabolism is firmly
      established. Integral to our understanding of transferrin, studies in
      hypotransferrinemic mice, a model of inherited transferrin deficiency, have
      demonstrated that transferrin is essential for iron delivery for erythropoiesis
      and in the regulation of expression of hepcidin, a hormone that inhibits
      macrophage and enterocyte iron efflux. Here we investigate a potential role for
      transferrin in the distribution of three other physiologic metals, manganese,
      copper, and zinc. We first assessed metal content in transferrin-rich fractions
      of wild-type mouse sera and demonstrate that although both iron and manganese
      cofractionated predominantly with transferrin, the absolute levels of manganese
      are several orders of magnitude lower than those of iron. We next measured metal
      content in multiple tissues in wild-type and hypotransferrinemic mice of various
      ages. Tissue metal imbalances were severe for iron and minimal to moderate for
      some metals in some tissues in hypotransferrinemic mice. Metal levels measured in
      a transferrin-replete yet hepcidin-deficient and iron-loaded mouse strain
      suggested that the observed imbalances in tissue copper, zinc, and manganese
      levels were not all specific to hypotransferrinemic mice or caused directly by
      transferrin deficiency. Overall, our results suggest that transferrin does not
      have a primary role in the distribution of manganese, copper, or zinc to tissues
      and that the abnormalities observed in tissue manganese levels are not
      attributable to a direct role for transferrin in manganese metabolism but rather
      are attributable to an indirect effect of transferrin deficiency on hepcidin
      expression and/or iron metabolism.

PMID- 24567068
TI  - Shoulder biomechanics and the success of translational research.
AB  - In 2009, the International Shoulder Group (ISG) had the opportunity to propose to
      the readers of Medical and Biological Engineering and Computing a Special Issue
      on shoulder biomechanics. At that time, we pointed out that the field was
      evolving to include more applied research. After 4 years, we can confirm that
      impression: 10 out of 12 papers included in this second Special Issue deal with
      clinical related questions, through theoretical and experimental methodologies.
      This demonstrates that the translational research at the base of ISG foundation
      in 1989 is effective. We think that the papers of this issue will have an impact
      on clinics in general and on the treatment of work-related injuries and diseases
      in particular. Based on the statistics of the Italian Workers' Compensation
      Authority (INAIL), injuries at the shoulder are first in terms of average
      duration of "temporary total disability to work". Moreover, occupational diseases
      at the shoulder in the industrial and services sector represented 16 % of all
      occupational diseases in 2012, i.e., 46 % of those related to the upper limb.
      These data stress the need for specific interventions, with the contribution of
      both researchers and policy makers. Starting from the papers included here, we
      would encourage additional efforts on: (1) quantitative analysis of shoulder
      loading during tasks associated with musculoskeletal injuries, and ways to reduce
      that loading, (2) simple and effective tools to improve the diagnosis and outcome
      assessment of motion-related shoulder diseases, and (3) the development of
      rehabilitation treatments focused on occupational tasks, taking advantage of
      state-of-the-art biofeedback technologies, and exploiting the power of
      biomechanical models for muscle force prediction. 

PMID- 24567070
TI  - Setting Win Limits: An Alternative Approach to "Responsible Gambling"?
AB  - Social scientists, governments, and the casino industry have all emphasized the
      need for casino patrons to "gamble responsibly." Strategies for responsible
      gambling include self-imposed time limits and loss limits on gambling. Such
      strategies help prevent people from losing more than they can afford and may help
      prevent excessive gambling behavior. Yet, loss limits also make it more likely
      that casino patrons leave when they are losing. Oddly, the literature makes no
      mention of "win limits" as a potential approach to responsible gambling. A win
      limit would be similar to a loss limit, except the gambler would leave the casino
      upon reaching a pre-set level of winnings. We anticipate that a self-imposed win
      limit will reduce the gambler's average loss and, by default, also reduce the
      casino's profit. We test the effect of a self-imposed win limit by running slot
      machine simulations in which the treatment group of players has self-imposed and
      self-enforced win and loss limits, while the control group has a self-imposed
      loss limit or no limit. We find that the results conform to our expectations: the
      win limit results in improved player performance and reduced casino profits.
      Additional research is needed, however, to determine whether win limits could be
      a useful component of a responsible gambling strategy. 

PMID- 24567071
TI  - A method for spatially explicit representation of sub-watershed sediment yield,
      Southern California, USA.
AB  - We present here a method to integrate geologic, topographic, and land-cover data
      in a geographic information system to provide a fine-scale, spatially explicit
      prediction of sediment yield to support management applications. The method is
      fundamentally qualitative but can be quantified using preexisting sediment-yield
      data, where available, to verify predictions using other independent data sets.
      In the 674-km(2) Sespe Creek watershed of southern California, 30 unique
      "geomorphic landscape units" (GLUs, defined by relatively homogenous areas of
      geology, hillslope gradient, and land cover) provide a framework for
      discriminating relative rates of sediment yield across this landscape. Field
      observations define three broad groupings of GLUs that are well-associated with
      types, relative magnitudes, and rates of erosion processes. These relative rates
      were then quantified using sediment-removal data from nearby debris basins, which
      allow relatively low-precision but robust calculations of both local and whole
      watershed sediment yields, based on the key assumption that minimal sediment
      storage throughout most of the watershed supports near-equivalency of long-term
      rates of hillslope sediment production and watershed sediment yield. The accuracy
      of these calculations can be independently assessed using geologically inferred
      uplift rates and integrated suspended sediment measurements from mainstem Sespe
      Creek, which indicate watershed-averaged erosion rates between about 0.6-1.0 mm
      year(-1) and corresponding sediment yields of about 2 * 10(3) t km(-2) year(-1).
      A spatially explicit representation of sediment production is particularly useful
      in a region where wildfires, rapid urban development, and the downstream delivery
      of upstream sediment loads are critical drivers of both geomorphic processes and
      land-use management. 

PMID- 24567069
TI  - Proteomics and diabetic nephropathy: what have we learned from a decade of
      clinical proteomics studies?
AB  - Diabetic nephropathy (DN) has become the most frequent cause of chronic kidney
      disease worldwide due to the constant increase of the incidence of type 2
      diabetes mellitus in developed and developing countries. The understanding of the
      pathophysiological mechanisms of human diseases through a large-scale
      characterization of the protein content of a biological sample is the key feature
      of the proteomics approach to the study of human disease. We discuss the main
      results of over 10 years of tissue and urine proteomics studies applied to DN in
      order to understand how far we have come and how far we still have to go before
      obtaining a full comprehension of the molecular mechanisms involved in the
      pathogenesis of DN and identifying reliable biomarkers for accurate management of
      patients.

PMID- 24567072
TI  - Mitochondrially targeted ZFNs for selective degradation of pathogenic
      mitochondrial genomes bearing large-scale deletions or point mutations.
AB  - We designed and engineered mitochondrially targeted obligate heterodimeric zinc
      finger nucleases (mtZFNs) for site-specific elimination of pathogenic human
      mitochondrial DNA (mtDNA). We used mtZFNs to target and cleave mtDNA harbouring
      the m.8993T>G point mutation associated with neuropathy, ataxia, retinitis
      pigmentosa (NARP) and the "common deletion" (CD), a 4977-bp repeat-flanked
      deletion associated with adult-onset chronic progressive external ophthalmoplegia
      and, less frequently, Kearns-Sayre and Pearson's marrow pancreas syndromes.
      Expression of mtZFNs led to a reduction in mutant mtDNA haplotype load, and
      subsequent repopulation of wild-type mtDNA restored mitochondrial respiratory
      function in a CD cybrid cell model. This study constitutes proof-of-principle
      that, through heteroplasmy manipulation, delivery of site-specific nuclease
      activity to mitochondria can alleviate a severe biochemical phenotype in primary
      mitochondrial disease arising from deleted mtDNA species. 

PMID- 24567074
TI  - Intraoperative Monitoring of Hearing Improvement during Ossiculoplasty by Laser
      Doppler Vibrometry, Auditory Brainstem Responses, and Electrocochleography.

PMID- 24567073
TI  - Metabolic crosstalk between the heart and liver impacts familial hypertrophic
      cardiomyopathy.
AB  - Familial hypertrophic cardiomyopathy (HCM) is largely caused by dominant
      mutations in genes encoding cardiac sarcomeric proteins, and it is etiologically
      distinct from secondary cardiomyopathies resulting from pressure/volume overload
      and neurohormonal or inflammatory stimuli. Here, we demonstrate that decreased
      left ventricular contractile function in male, but not female, HCM mice is
      associated with reduced fatty acid translocase (CD36) and AMP-activated protein
      kinase (AMPK) activity. As a result, the levels of myocardial ATP and
      triglyceride (TG) content are reduced, while the levels of oleic acid and TG in
      circulating very low density lipoproteins (VLDLs) and liver are increased. With
      time, these metabolic changes culminate in enhanced glucose production in male
      HCM mice. Remarkably, restoration of ventricular TG and ATP deficits via AMPK
      agonism as well as inhibition of gluconeogenesis improves ventricular
      architecture and function. These data underscore the importance of the systemic
      effects of a primary genetic heart disease to other organs and provide insight
      into potentially novel therapeutic interventions for HCM. 

PMID- 24567075
TI  - Do monkeys choose to choose?
AB  - Both empirical and anecdotal evidence supports the idea that choice is preferred
      by humans. Previous research has demonstrated that this preference extends to
      nonhuman animals, but it remains largely unknown whether animals will actively
      seek out or prefer opportunities to choose. Here we explored the issue of whether
      capuchin and rhesus monkeys choose to choose. We used a modified version of the
      SELECT task-a computer program in which monkeys can choose the order of
      completion of various psychomotor and cognitive tasks. In the present
      experiments, each trial began with a choice between two icons, one of which
      allowed the monkey to select the order of task completion, and the other of which
      led to the assignment of a task order by the computer. In either case, subjects
      still had to complete the same number of tasks and the same number of task
      trials. The tasks were relatively easy, and the monkeys responded correctly on
      most trials. Thus, global reinforcement rates were approximately equated across
      conditions. The only difference was whether the monkey chose the task order or it
      was assigned, thus isolating the act of choosing. Given sufficient experience
      with the task icons, all monkeys showed a significant preference for choice when
      the alternative was a randomly assigned order of tasks. To a lesser extent, some
      of the monkeys maintained a preference for choice over a preferred, but computer
      assigned, task order that was yoked to their own previous choice selection. The
      results indicated that monkeys prefer to choose when all other aspects of the
      task are equated. 

PMID- 24567076
TI  - National hospice survey results: for-profit status, community engagement, and
      service.
AB  - IMPORTANCE The impact of the substantial growth in for-profit hospices in the
      United States on quality and hospice access has been intensely debated, yet
      little is known about how for-profit and nonprofit hospices differ in activities
      beyond service delivery. OBJECTIVE To determine the association between hospice
      ownership and (1) provision of community benefits, (2) setting and timing of the
      hospice population served, and (3) community outreach. DESIGN, SETTING, AND
      PARTICIPANTS Cross-sectional survey (the National Hospice Survey), conducted from
      September 2008 through November 2009, of a national random sample of 591 Medicare
      certified hospices operating throughout the United States. EXPOSURES For-profit
      or nonprofit hospice ownership. MAIN OUTCOMES AND MEASURES Provision of community
      benefits; setting and timing of the hospice population served; and community
      outreach. RESULTS A total of 591 hospices completed our survey (84% response
      rate). For-profit hospices were less likely than nonprofit hospices to provide
      community benefits including serving as training sites (55% vs 82%; adjusted
      relative risk [ARR], 0.67 [95% CI, 0.59-0.76]), conducting research (18% vs 23%;
      ARR, 0.67 [95% CI, 0.46-0.99]), and providing charity care (80% vs 82%; ARR, 0.88
      [95% CI, 0.80-0.96]). For-profit compared with nonprofit hospices cared for a
      larger proportion of patients with longer expected hospice stays including those
      in nursing homes (30% vs 25%; P = .009). For-profit hospices were more likely to
      exceed Medicare's aggregate annual cap (22% vs 4%; ARR, 3.66 [95% CI, 2.02-6.63])
      and had a higher patient disenrollment rate (10% vs 6%; P < .001). For-profit
      were more likely than nonprofit hospices to engage in outreach to low-income
      communities (61% vs 46%; ARR, 1.23 [95% CI, 1.05-1.44]) and minority communities
      (59% vs 48%; ARR, 1.18 [95% CI, 1.02-1.38]) and less likely to partner with
      oncology centers (25% vs 33%; ARR, 0.59 [95% CI, 0.44-0.80]). CONCLUSIONS AND
      RELEVANCE Ownership-related differences are apparent among hospices in community
      benefits, population served, and community outreach. Although Medicare's
      aggregate annual cap may curb the incentive to focus on long-stay hospice
      patients, additional regulatory measures such as public reporting of hospice
      disenrollment rates should be considered as the share of for-profit hospices in
      the United States continues to increase. 

PMID- 24567077
TI  - Influence of the number of topologically interacting neighbors on swarm dynamics.
AB  - Recent empirical and theoretical works on collective behaviors based on a
      topological interaction are beginning to offer some explanations as for the
      physical reasons behind the selection of a particular number of nearest neighbors
      locally affecting each individual's dynamics. Recently, flocking starlings have
      been shown to topologically interact with a very specific number of neighbors,
      between six to eight, while metric-free interactions were found to govern human
      crowd dynamics. Here, we use network- and graph-theoretic approaches combined
      with a dynamical model of locally interacting self-propelled particles to study
      how the consensus reaching process and its dynamics are influenced by the number
      k of topological neighbors. Specifically, we prove exactly that, in the absence
      of noise, consensus is always attained with a speed to consensus strictly
      increasing with k. The analysis of both speed and time to consensus reveals that,
      irrespective of the swarm size, a value of k ~ 10 speeds up the rate of
      convergence to consensus to levels close to the one of the optimal all-to-all
      interaction signaling. Furthermore, this effect is found to be more pronounced in
      the presence of environmental noise. 

PMID- 24567078
TI  - Functions and mechanisms of intermittent negative pressure for osteogenesis in
      human bone marrow mesenchymal stem cells.
AB  - The present study aimed to determine the mechanism by which low-intensity
      intermittent negative pressure affects the differentiation and proliferation of
      human mesenchymal stem cells (MSCs). Alkaline phosphatase (ALP) activity, type I
      collagen and vascular endothelial growth factor (VEGF) were detected to analyze
      differentiation. MTT and flow cytometry were employed to measure proliferation
      and apoptosis. Western blot analysis was used to examine endoplasmic reticulum
      (ER) stress-associated factors. This study was divided into two groups, including
      a normal group (without any treatment) and vacuum group (treated with a vacuum).
      There was a significant decrease in the proliferation of cells in the vacuum
      group. The number of cells in S phase was reduced significantly, while the rate
      of apoptosis and the activity of ALP were markedly increased under vacuum
      conditions. Expression of collagen type I and VEGF was significantly increased,
      and the ratio of osteoprotegrin to osteoprotegrin ligand was decreased
      significantly in the vacuum group. ER stress-associated proteins, p-PRKR-like ER
      kinase, inositol-requiring enzyme 1 and cleaved activating transcription factor
      6, as well as the downstream factors, were activated when treated with negative
      pressure. In conclusion, treatment with low-intensity and intermittent negative
      pressure may inhibit the proliferation of MSCs and trigger ER stress-associated
      cellular apoptosis, further enhancing osteogenesis activity and inducing
      differentiation to osteoblasts.

PMID- 24567079
TI  - Pseudomonas sihuiensis sp. nov., isolated from a forest soil in South China.
AB  - A Gram-stain negative, motile, rod-shaped bacterium, designated strain WM-2(T),
      was isolated from a forest soil in Sihui City, South China, and characterized by
      means of a polyphasic approach. Growth occurred with 0-5 % (w/v) NaCl (optimum 0
      1 %) and at pH 5.0-10.5 (optimum pH 8.5) and 4-40  degrees C (optimum 30  degrees
      C) in Luria-Bertani medium. Comparative 16S rRNA gene sequence analyses showed
      that strain WM-2(T) is a member of the genus Pseudomonas and most closely related
      to P. guguanensis, P. oleovorans subsp. lubricantis, P. toyotomiensis, P.
      alcaliphila and P. mendocina with 97.1-96.6 % sequence similarities. In terms of
      gyrB and rpoB gene sequences, strain WM-2(T) showed the highest similarity with
      the type strains of the species P. toyotomiensis and P. alcaliphila. The DNA-DNA
      relatedness values of strain WM-2(T) with P. guguanensis and P. oleovorans subsp.
      lubricantis was 48.7 and 37.2 %, respectively. Chemotaxonomic characteristics
      (the main ubiquinone Q-9, major fatty acids C18:1 omega7c/C18:1 omega6c, C16:0
      and C16:1 omega7c/C16:1 omega6c and DNA G+C content 65.2 +/- 0.7 mol%) were
      similar to those of members of the genus Pseudomonas. Polar lipids consisted of
      diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, an
      unknown aminophospholipid, an unknown phospholipid and five unknown lipids.
      According to the results of polyphasic analyses, strain WM-2(T) represents a
      novel species in the genus Pseudomonas, for which the name Pseudomonas sihuiensis
      sp. nov. is proposed. The type strain is WM-2(T) (=KCTC 32246(T)=CGMCC
      1.12407(T)).

PMID- 24567081
TI  - Examining construct and predictive validity of the Health-IT Usability Evaluation
      Scale: confirmatory factor analysis and structural equation modeling results.
AB  - BACKGROUND: In a previous study, we developed the Health Information Technology
      Usability Evaluation Scale (Health-ITUES), which is designed to support
      customization at the item level. Such customization matches the specific
      tasks/expectations of a health IT system while retaining comparability at the
      construct level, and provides evidence of its factorial validity and internal
      consistency reliability through exploratory factor analysis. OBJECTIVE: In this
      study, we advanced the development of Health-ITUES to examine its construct
      validity and predictive validity. METHODS: The health IT system studied was a web
      based communication system that supported nurse staffing and scheduling. Using
      Health-ITUES, we conducted a cross-sectional study to evaluate users' perception
      toward the web-based communication system after system implementation. We
      examined Health-ITUES's construct validity through first and second order
      confirmatory factor analysis (CFA), and its predictive validity via structural
      equation modeling (SEM). RESULTS: The sample comprised 541 staff nurses in two
      healthcare organizations. The CFA (n=165) showed that a general usability factor
      accounted for 78.1%, 93.4%, 51.0%, and 39.9% of the explained variance in
      'Quality of Work Life', 'Perceived Usefulness', 'Perceived Ease of Use', and
      'User Control', respectively. The SEM (n=541) supported the predictive validity
      of Health-ITUES, explaining 64% of the variance in intention for system use.
      CONCLUSIONS: The results of CFA and SEM provide additional evidence for the
      construct and predictive validity of Health-ITUES. The customizability of Health
      ITUES has the potential to support comparisons at the construct level, while
      allowing variation at the item level. We also illustrate application of Health
      ITUES across stages of system development.

PMID- 24567082
TI  - Expression patterns of c-Fos early gene and phosphorylated ERK in the rat brain
      following 1-h immobilization stress: concomitant changes induced in association
      with stress-related sleep rebound.
AB  - An immobilization stress (IS) of 1 h applied at the beginning of the dark phase
      is followed by a sleep rebound. During the restraint, serotonin released by the
      dorsal raphe nucleus within the arcuate area stimulates the availability of
      corticotropin-like intermediate lobe peptide (CLIP or ACTH18-39). Three hours
      after the restraint, CLIP, through its hypnogenic properties, contributes to the
      sleep rebound that follows the IS. Here, we immunohistochemically evaluated
      protein expression of the immediate early gene, c-Fos and phosphorylated
      extracellular signal-regulated kinase (p-ERK) in hypothalamic (preoptic area
      [POA], paraventricular nucleus [PVN], arcuate nucleus [ARC]) and brain stem
      (dorsal raphe [DR], locus coeruleus [LC]) nuclei involved in the acute response
      to stress and the subsequent stress-related sleep rebound (recovery period).
      Immediately after the 1-h restraint, c-Fos and p-ERK expression increased in all
      structures studied, particularly in PVN and LC. Three hours later, the number of
      p-ERK- and c-Fos-positive neurons was reduced in PVN and LC (p < 0.001) as well
      as in DR (p < 0.01) compared to control animals. In contrast, both c-Fos and p
      ERK expression in POA neurons (p < 0.01) and c-Fos expression in ARC neurons (p <
      0.001) were increased 3 h after the IS. The marked activation observed in PVN and
      LC nucleus immediately after the IS confirms that these structures are clearly
      reactive to stress. However, the high activity observed in POA and ARC neurons
      during the recovery period, not described to date, highlights the particular part
      played by these structures in the stress-related sleep rebound. An unbalance in
      the above processes may contribute to pathological outcomes, such as anxiety and
      depression.

PMID- 24567084
TI  - Dispersion and characterization of arc discharge single-walled carbon nanotubes-
      towards conducting transparent films.
AB  - This study addresses a combination of a well-developed and mild dispersion method
      and high-quality arc discharge single-walled carbon nanotubes (SWCNTs) as
      starting materials. Thus, we advance in fabrication of transparent, conducting
      films with extraordinary low material loss during SWCNT processing. The starting
      material was characterized by means of thermogravimetric analysis, high
      resolution transmission electron microscopy and Raman spectroscopy. The quality
      of the starting material and produced dispersions was evaluated by ultraviolet
      and visible light absorption spectroscopy and Raman spectroscopy. A transparent
      conductive film was fabricated by drop-casting, whereas films were obtained with
      electrical to optical conductivity ratios (sigmaDC/sigmaOp) as high as 2.2,
      combined with a loss of nanotube material during processing well below 20 wt%.
      High pressure carbon monoxide conversion (HiPCO) SWCNTs, which are very well
      described in the literature, were used for comparison. 

PMID- 24567080
TI  - Roseivivax atlanticus sp. nov., isolated from surface seawater of the Atlantic
      Ocean.
AB  - A taxonomic study was carried out on strain 22II-S10s(T), which was isolated from
      the surface seawater of the Atlantic Ocean. The bacterium was found to be Gram
      negative, oxidase and catalase positive, rod shaped and motile by subpolar
      flagella. The isolate was capable of gelatine hydrolysis but unable to reduce
      nitrate to nitrite or degrade Tween 80 or aesculin. Growth was observed at
      salinities of 0.5-18 % (optimum, 2-12 %), at pH of 3-10 (optimum, 7) and at
      temperatures of 10-41  degrees C (optimum 28  degrees C). Phylogenetic analysis
      based on 16S rRNA gene sequences indicated that strain 22II-S10s(T) belongs to
      the genus Roseivivax, with highest sequence similarity to Roseivivax halodurans
      JCM 10272(T) (97.2 %), followed by Roseivivax isoporae LMG 25204(T) (97.0 %);
      other species of genus Roseivivax shared 95.2-96.7 % sequence similarity. The DNA
      DNA hybridization estimate values between strain 22II-S10s(T) and the two type
      strains (R. halodurans JCM 10272(T) and R. isoporae LMG 25204(T)) were 22.00 and
      21.40 %. The principal fatty acids were identified as Summed Feature 8 (C18:1
      omega7c/omega6c) (67.4 %), C18:0 (7.2 %), C19:0 cyclo omega8c (7.1 %), C18:1
      omega7c 11-methyl (6.8 %) and C16:0 (5.9 %). The respiratory quinone was
      determined to be Q-10 (100 %). Phosphatidylcholine, phosphatidylethanolamine,
      phosphatidylglycerol, an aminolipid, a glycolipid and three phospholipids were
      present. The G+C content of the chromosomal DNA was determined to be 67.5 mol%.
      The combined genotypic and phenotypic data show that strain 22II-S10s(T)
      represents a novel species within the genus Roseivivax, for which the name
      Roseivivax atlanticus sp. nov. is proposed, with the type strain 22II-S10s(T) (=
      MCCC 1A09150(T) = LMG 27156(T)). 

PMID- 24567085
TI  - Prostate cancer: The role of local therapy for metastatic prostate cancer.

PMID- 24567086
TI  - Penile cancer: Developments in sentinel lymph node biopsy for penile cancer.

PMID- 24567087
TI  - Bladder cancer: Potentially fewer minor complications with RARC than ORC but at
      what cost?

PMID- 24567088
TI  - Kidney cancer: Intratumoral differences analysed.

PMID- 24567089
TI  - Paediatrics: to screen or not to screen--the role of VCUG in infant UTI.

PMID- 24567090
TI  - Bladder cancer: Genetic studies mark change in fortune for bladder cancer.

PMID- 24567092
TI  - General in vitro caspase assay procedures.
AB  - One of the most valuable tools that have been developed for the study of
      apoptosis is the availability of recombinant active caspases. The determination
      of caspase substrate preference, the design of sensitive substrates and potent
      inhibitors, the resolution of caspase structures, the elucidation of their
      activation mechanisms, and the identification of their substrates were made
      possible by the availability of sufficient amounts of enzymatically pure
      caspases. The current chapter describes at length the expression, purification,
      and basic enzymatic characterization of apoptotic caspases. 

PMID- 24567091
TI  - Efficacy of systemic thrombolysis within 4.5 h from stroke symptom onset: a
      single-centre clinical and diffusion-perfusion 3T MRI study.
AB  - PURPOSE: The efficacy of thrombolytic treatment with recombinant tissue
      plasminogen activator (rt-PA) within 3 h from stroke onset has been extensively
      supported by randomised placebo-controlled multicentre trials. In our single
      centre study, we investigated the efficacy of intravenous (IV) administration of
      rt-PA within 4.5 h of stroke onset, in terms of clinical and radiological
      outcome, using a 3T magnetic resonance (MR) scanner in a cohort of patients
      similar to that of multicentre clinical trials. MATERIALS AND METHODS:
      Consecutive patients treated with IV rt-PA were compared with an historical
      cohort of untreated patients (controls). Inclusion criteria were: (1) infarction
      of the middle cerebral artery territory, (2) eligibility for IV rt-PA treatment,
      and (3) 3T perfusion- and diffusion-weighted MR imaging and MR angiography
      performed within 4.5 h and repeated after 5-7 days. Stroke severity was assessed
      with the National Institutes of Health Stroke Scale (NIHSS). Growth of the DWI
      lesion, saved hypoperfused tissue, and clinical outcome was assessed and compared
      in treated patients and controls. RESULTS: Forty-three patients treated with rt
      PA and 69 controls were eligible for the analysis. Treated patients showed higher
      percentages of saved hypoperfused tissue (75 vs. 40 %; p = 0.009), vessel
      recanalisation (65 vs. 27.5%; p = 0.003), and haemorrhagic transformation (21 vs.
      7%; p = 0.004), without any clinically significant haemorrhages. Furthermore,
      treated patients had a significant improvement of NIHSS at 24 h (p < 0.001), at
      discharge (p <= 0.001), and at the 3-month clinical evaluation (p < 0.001), while
      similar rates of both treated patients and controls achieved a 3-month modified
      Rankin scale <= 2 (62 and 65%; p = 0.7). CONCLUSION: Treatment with IV rt-PA
      within 4.5 h of stroke onset preserves a significant amount of brain tissue from
      final infarction, and increases the possibility of early and late clinical
      improvement.

PMID- 24567093
TI  - Positional scanning substrate combinatorial library (PS-SCL) approach to define
      caspase substrate specificity.
AB  - Positional scanning substrate combinatorial library (PS-SCL) is a powerful tool
      for studying substrate specificity of proteolytic enzymes. Here, we describe the
      protocol for analyzing S4-S2 pockets preferences of caspases using PS-SCL.
      Additionally, we describe procedures for the identification of optimal substrates
      sequence after PS-SCL, solid phase synthesis, and purification of selected
      fluorogenic substrates, as well as their kinetic analysis. 

PMID- 24567094
TI  - Global identification of caspase substrates using PROTOMAP (protein topography
      and migration analysis platform).
AB  - Delineation of the natural substrate scope of proteases is important for
      understanding the functions of proteolytic pathways in physiology and disease.
      Herein we describe the protocol for PROTOMAP, a technique that combines SDS-PAGE
      with tandem mass spectrometry to globally identify shifts in protein migration
      indicative of proteolytic processing. When applied to cells undergoing apoptosis,
      this unbiased global method provides a snapshot of the topography and magnitude
      of proteolytic events associated with programmed cell death. 

PMID- 24567095
TI  - Caspase-2 protocols.
AB  - Caspase-2 has been shown to function in apoptosis and in some non-apoptotic
      pathways, including tumor suppression and aging. Caspase-2 has some unique
      features and is the only caspase that constitutively localizes to the nucleus,
      although its nuclear function remains unknown. During apoptosis signaling,
      caspase-2 rapidly homodimerizes, which leads to its activation and proteolytic
      processing. The activation of caspase-2 can be measured by assessing its
      dimerization and/or cleavage of the caspase-2 zymogen and its substrates. This
      chapter outlines commonly used methods to purify recombinant caspase-2 and assess
      its activity and function in vitro and in cultured cells or tissue extracts. 

PMID- 24567096
TI  - Caspase-14 protocols.
AB  - Unlike other caspase family members, caspase-14 shows restricted expression,
      being found mostly in epidermis and its appendages. It has been suggested that
      caspase-14 is not involved in apoptosis or inflammation, but participates in
      keratinocyte terminal differentiation. Its activation occurs at the corneocyte
      formation. In previous work, we have purified active caspase-14 from human
      corneocyte extracts. In addition, we have clarified activation mechanism of
      caspase-14, where kallikrein-related peptidase 7 (KLK7) generates an intermediate
      form from procaspase-14 and this form finally converts procaspase-14 to active,
      mature caspase-14. Here we describe techniques for measurement of caspase-14
      activity using synthetic substrate, purification of caspase-14 from corneocyte
      extract, preparation of constitutively active caspase-14 and specific antibody,
      quantification of total and active caspase-14 in corneocyte extracts using ELISA,
      as well as methods for caspase-14 activation and its visualization by
      immunohistochemistry. 

PMID- 24567097
TI  - Caspase protocols in Caenorhabditis elegans.
AB  - Caenorhabditis elegans genome has four genes (ced-3, csp-1, csp-2, and csp-3)
      encoding caspase-like proteins. Among these four proteins, CED-3 is the most well
      known cell-killing caspase. Elucidation of the role of CED-3 as a central
      component of the apoptotic pathway in C. elegans has contributed to the
      understanding of the more complex apoptosis network in mammals and in other
      metazoa. In the highly conserved pathway of programmed cell death in C. elegans,
      CED-3 functions at the terminal step of this cell-killing pathway. Identification
      of CED-3 caspase substrates is essential for bridging the gaps between CED-3
      activation and various downstream cell death execution events. If a protein is
      cleaved by CED-3 in vitro, this protein could be a potential CED-3 substrate in
      vivo. Here, we describe the method for purification of active CED-3 caspase. We
      will also describe in vitro assays for determining CED-3 proteolytic activity,
      CED-3 substrates, and CED-3 cleavage sites in the substrates. 

PMID- 24567098
TI  - Detecting caspase activity in Drosophila larval imaginal discs.
AB  - Caspases are a highly specialized class of cell death proteases. Since they are
      synthesized as inactive full-length zymogens, activation--at least of effector
      caspases and to some extent also of initiator caspases-requires a proteolytic
      cleavage event, generating a large and a small subunit, two of each forming the
      active caspase. The proteolytic cleavage event generates neo-epitopes at both the
      C-terminus of the large subunit and the N-terminus of the small subunit. The
      cleaved Caspase-3 (CC3) antibody was raised against the neo-epitope of the large
      subunit and thus detects only cleaved, but not full-length, Caspase-3. Although
      raised against human cleaved Caspase-3, the CC3 antibody cross-reacts in other
      species and detects cleaved caspases, most notably DrICE and Dcp-1, in
      Drosophila. This protocol describes the procedure for use of the CC3 antibody to
      detect caspase activity in larval imaginal discs in Drosophila.

PMID- 24567099
TI  - Methods for the study of caspase activation in the Xenopus laevis oocyte and egg
      extract.
AB  - The study of apoptosis and caspases has advanced greatly over recent decades.
      Studies conducted in the Xenopus laevis egg extract and oocyte model system have
      significantly contributed to these advances. Twenty years ago, Newmeyer and
      colleagues first showed that the X. laevis egg extract, when incubated at room
      temperature, reconstituted the key molecular events of cellular apoptosis
      including cytochrome c release, nuclear condensation, internucleosomal
      fragmentation, and caspase activation. The biochemical tractability of the egg
      extract system allows for robust study of apoptotic events and caspase
      activation. Its nature as a cell-free extract system allows substrates to be very
      simply added by pipette, and their effects on apoptosis and caspase activation
      and their placement in the apoptotic signaling pathway (e.g., pre- or post
      mitochondrial) are subsequently very simply studied using the techniques
      described in this chapter. Also described in this chapter are assays that allow
      the study of caspase activation in intact oocytes, another valuable tool
      available when using the X. laevis model organism. Overall, the X. laevis egg
      extract/oocyte model is a robust, efficient, and biochemically tractable system
      that is ideal for the study of apoptosis and caspase activation. 

PMID- 24567101
TI  - Measurement of caspase activation in mammalian cell cultures.
AB  - The majority of caspases, cysteine-dependent aspartate-directed proteases, being
      in their activated state are involved in regulation of apoptosis by cleaving
      protein substrates harboring specific target motifs. Basically all biochemical
      and morphological changes in an apoptotic cell, including cell shrinkage,
      chromatin condensation, DNA fragmentation, and plasma membrane blebbing, are
      consequence of caspase-mediated proteolysis. Thus, uncovering activities of
      unique caspases are key determinants of the apoptotic process. This chapter
      describes a set of experimental protocols available for characterization,
      quantification and inhibition of caspase activities in mammalian cell cultures,
      including immunoblotting, usage of synthetic substrates, flow cytometry, and
      microscopic techniques. 

PMID- 24567100
TI  - Caspase protocols in mice.
AB  - Members of the caspase family of proteases are evolutionarily conserved cysteine
      proteases that play a crucial role as the central executioners of the apoptotic
      pathway. Since the discovery of caspases, many methods have been developed to
      detect their activation and are widely used in basic and clinical studies. In a
      mouse tissue, caspase activation can be monitored by cleavage of caspase-specific
      synthetic substrates and by detecting cleaved caspase by western blot analysis of
      the tissue extract. In tissue sections, active caspase can be detected by
      immunostaining using specific antibodies to the active caspase. In addition,
      among the myriads of caspase-specific substrates known so far, cleaved fragments
      produced by caspases from the substrates such as PARP, lamin A, and cytokeratin
      18 can be monitored in tissue sections by immunostaining as well as western blots
      of tissue extracts. In general, more than one method should be used to ascertain
      detection of activation of caspases in a mouse tissue. 

PMID- 24567102
TI  - Detection and measurement of paracaspase MALT1 activity.
AB  - The paracaspase MALT1 is a Cys-dependent, Arg-specific protease that plays an
      essential role in the activation and proliferation of lymphocytes during the
      immune response. Oncogenic activation of MALT1 is associated with the development
      of specific forms of B-cell lymphomas. Through specific cleavage of its
      substrates, MALT1 controls various aspects of lymphocyte activation, including
      the activation of transcriptional pathways, the stabilization of mRNAs, and an
      increase in cellular adhesion. In lymphocytes, the activity of MALT1 is tightly
      controlled by its inducible monoubiquitination, which promotes the dimerization
      of MALT1. Here, we describe both in vitro and in vivo assays that have been
      developed to assess MALT1 activity. 

PMID- 24567103
TI  - Leishmania metacaspase: an arginine-specific peptidase.
AB  - The purpose of this chapter is to give insights into metacaspase of Leishmania
      protozoan parasites as arginine-specific cysteine peptidase. The physiological
      role of metacaspase in Leishmania is still a matter of debate, whereas its
      peptidase enzymatic activity has been well characterized. Among the different
      possible expression systems, metacaspase-deficient yeast cells (Deltayca1) have
      been instrumental in studying the activity of Leishmania major metacaspase
      (LmjMCA). Here, we describe techniques for purification of LmjMCA and its
      activity measurement, providing a platform for further identification of LmjMCA
      substrates. 

PMID- 24567104
TI  - Purification, characterization, and crystallization of Trypanosoma metacaspases.
AB  - Metacaspases are cysteine peptidases found in trypanosomes but absent in mammals,
      and despite being distantly related to the mammalian caspases they show
      significant disparity in their cellular and enzymatic functions. The genome of
      the parasitic protozoa Trypanosoma brucei (the causative agent of African
      sleeping sickness) encodes five metacaspases: TbMCA1-TbMCA5. Of these TbMCA2,
      TbMCA3, and TbMCA5 are active cysteine peptidases expressed in the bloodstream
      form of the parasite. To investigate the structure-function relationship of the
      trypanosome metacaspases and the structural basis for their divergence from the
      caspases, paracaspases, and other Clan CD cysteine peptidases (or vice versa), we
      purified and characterized TbMCA2 and determined the three-dimensional structure
      of an inactive mutant using X-ray crystallography. The methods presented in this
      chapter describe the recombinant expression of active TbMCA2 and inactive
      TbMCA2(C213A). The protocols produce large amounts of recombinant protein for use
      in structural, biochemical, and kinetic studies and include detailed information
      on how to produce diffraction quality crystals of TbMCA2(C213A). 

PMID- 24567105
TI  - Monitoring the proteostasis function of the Saccharomyces cerevisiae metacaspase
      Yca1.
AB  - The functional versatility of metacaspase proteases has been established by
      reports of their involvement in non-apoptotic cellular processes, in addition to
      their canonical role in apoptosis/programmed cell death. While the budding yeast
      metacaspase Yca1 has been well characterized for its role in cell death
      regulation, more recent examinations suggest that the protease may be involved in
      key processes that increase survival and fitness. More specifically, examinations
      suggest that Yca1 is central to maintaining cellular proteostasis as it interacts
      with major components involved in protein biosynthesis and functions to limit
      aggregate deposition. Here, we describe the methods utilized to analyze the role
      Yca1 in proteostasis. 

PMID- 24567106
TI  - Plant metacaspase activation and activity.
AB  - Metacaspases are essential for cell death regulation in plants. Further
      understanding of biochemistry of metacaspases and their molecular function in
      plant biology requires a set of robust methods for detection of metacaspase
      activation and quantitative analysis of corresponding proteolytic activity. Here
      we describe methods for purification of recombinant metacaspases, measurement of
      enzymatic activity of recombinant and endogenous metacaspases in vitro and in
      cell lysates, respectively, and finally detection of metacaspase activation in
      vivo. Additionally, an in vitro metacaspase protein substrate cleavage assay
      based on the cell-free production of substrate protein followed by proteolysis
      with recombinant metacaspase is presented. These methods have been originally
      developed for type II metacaspases from Arabidopsis and Norway spruce (Picea
      abies), but they can be used as templates for type I metacaspases, as well as for
      type II metacaspases from other species. 

PMID- 24567107
TI  - Preparation of Arabidopsis thaliana seedling proteomes for identifying
      metacaspase substrates by N-terminal COFRADIC.
AB  - Proteome-wide discovery of in vivo metacaspase substrates can be obtained by
      positional proteomics approaches such as N-terminal COFRADIC, for example by
      comparing the N-terminal proteomes (or N-terminomes) of wild-type plants to
      transgenic plants not expressing a given metacaspase. In this chapter we describe
      a protocol for the preparation of plant tissue proteomes, including differential
      isotopic labelling allowing for a comparison of in vivo N-terminomes that serves
      as the starting point for N-terminal COFRADIC studies. 

PMID- 24567108
TI  - The benzaldehyde oxidation paradox explained by the interception of peroxy
      radical by benzyl alcohol.
AB  - Benzaldehyde readily undergoes autoxidation to form benzoic acid on exposure to
      air at room temperature. Yet it can be formed in high yield from, for example,
      benzyl alcohol by oxidation using a variety of procedures and catalysts. Here we
      report the evidence to resolve this apparent paradox. It is confirmed that benzyl
      alcohol (and a number of other alcohols), even at low concentrations in
      benzaldehyde, inhibits the autoxidation. Furthermore we report on the structural
      features required for inhibition. Electron paramagnetic resonance spin trapping
      experiments demonstrate that benzyl alcohol intercepts, by hydrogen atom
      transfer, the benzoylperoxy radicals that play a key role in benzaldehyde
      autoxidation. A similar inhibition effect has also been observed for the
      aliphatic octanal/1-octanol system. 

PMID- 24567112
TI  - Correcting the correction of conditional recency slopes.
AB  - Farrell (Journal of Experimental Psychology: Learning, Memory, and Cognition, 36,
      324-347, 2010) presented some analyses of free recall data that suggest that
      recency items initially become more accessible as recall progresses, in contrast
      to the assumptions of temporal drift models. Moran and Goshen-Gottstein (2013)
      present some challenges to Farrell's (2010) analyses of the change in conditional
      recency across output position in free recall. Simulations using a very basic
      free recall model that controls conditional recency across recall show that
      Farrell's (2010) analyses are not substantially biased, while the procedure
      proposed by Moran and Goshen-Gottstein introduces a substantial underestimation
      of the true slopes. The null slopes observed in immediate recall by Moran and
      Goshen-Gottstein are not informative of the true slopes characterizing the data.
      Accordingly, Farrell's (2010) results continue to present a challenge to temporal
      drift models.

PMID- 24567111
TI  - Astragalosides attenuate learning and memory impairment in rats following
      ischemia-reperfusion injury.
AB  - Astragalosides (ASTs) have been traditionally used in the treatment of various
      cardiovascular and cerebrovascular diseases. The aim of the present study was to
      investigate the neuroprotective effects of AST on learning and memory following
      focal cerebral ischemia/reperfusion in a rat model. A Morris water maze was used
      to measure the effect of AST on learning and memory impairments. A histological
      examination and Hoechst 33258 staining was used to observe the neuronal changes
      and apoptosis in the hippocampus. The activity of phospho-extracellular signal
      regulated kinases (p-ERK), p-c-Jun N-terminal kinases (JNK) and p-Akt was
      measured by western blotting. The data revealed that AST improved the rats
      learning and memory abilities, attenuated neuronal cells apoptosis, increased the
      expression of p-ERK and p-Akt, and decreased the expression of p-JNK. These
      findings indicated that AST has protective effects that may be correlated with
      the inhibition of neuronal cell apoptosis and the regulation of p-ERK, p-Akt and
      p-JNK expression.

PMID- 24567113
TI  - Carboranes.

PMID- 24567110
TI  - Lipid transport in the lactating mammary gland.
AB  - Mammalian cells depend on phospholipid (PL) and fatty acid (FA) transport to
      maintain membrane structure and organization, and to fuel and regulate cellular
      functions. In mammary glands of lactating animals, copious milk secretion,
      including large quantities of lipid in some species, requires adaptation and
      integration of PL and FA synthesis and transport processes to meet secretion
      demands. At present few details exist about how these processes are regulated
      within the mammary gland. However, recent advances in our understanding of the
      structural and molecular biology of membrane systems and cellular lipid
      trafficking provide insights into the mechanisms underlying the regulation and
      integration of PL and FA transport processes the lactating mammary gland. This
      review discusses the PL and FA transport processes required to maintain the
      structural integrity and organization of the mammary gland and support its
      secretory functions within the context of current molecular and cellular models
      of their regulation.

PMID- 24567114
TI  - Dual roles of cadaverine-producing Pseudomonas sp. on Microcystis spp. in hyper
      eutrophic water.
AB  - A bacterium isolated from Lake Taihu was identified as Pseudomonas sp. A3CT,
      which performed different effects on Microcystis spp. Growth of Microcystis flos
      aquae and Microcystis aeruginosa was assessed in co-culture with A3CT to
      determine the stimulatory or inhibitory effects on these toxic, bloom-forming
      Microcystis strains. Results demonstrated that the impacts of A3CT were species
      specific. A3CT promoted the growth of M. aeruginosa but inhibited growth of M.
      flos-aquae. To investigate the cause of this phenomenon, the chemical composition
      of A3CT exudates and the impact of exposure to A3CT exudates on the two
      Microcystis species were determined. Results suggested that the observed
      differential growth responses of the two microalgae to A3CT exposure might be
      related to two components in A3CT exudates NH4 (+) and cadaverine. Growth
      stimulation of M. aeruginosa by A3CT was significantly related to NH4 (+)
      concentration. Cadaverine possibly acted as a growth inhibitor of M. flos-aquae.
      The different effects of cadaverine on growth of the two Microcystis strains
      suggested that A3CT might play a role in intrageneric succession patterns
      observed during Microcystis blooms in Lake Taihu.

PMID- 24567109
TI  - Nutrient transport in the mammary gland: calcium, trace minerals and water
      soluble vitamins.
AB  - Milk nutrients are secreted by epithelial cells in the alveoli of the mammary
      gland by several complex and highly coordinated systems. Many of these nutrients
      are transported from the blood to the milk via transcellular pathways that
      involve the concerted activity of transport proteins on the apical and
      basolateral membranes of mammary epithelial cells. In this review, we focus on
      transport mechanisms that contribute to the secretion of calcium, trace minerals
      and water soluble vitamins into milk with particular focus on the role of
      transporters of the SLC series as well as calcium transport proteins (ion
      channels and pumps). Numerous members of the SLC family are involved in the
      regulation of essential nutrients in the milk, such as the divalent metal
      transporter-1 (SLC11A2), ferroportin-1 (SLC40A1) and the copper transporter CTR1
      (SLC31A1). A deeper understanding of the physiology and pathophysiology of these
      transporters will be of great value for drug discovery and treatment of breast
      diseases.

PMID- 24567115
TI  - Prioritization of research addressing antipsychotics for adolescents and young
      adults with bipolar disorder.
AB  - Despite a paucity of high-quality evidence about benefits and harms,
      antipsychotic medication use among adolescents and young adults with bipolar
      disorder is increasing. The Patient-Centered Outcomes Research Institute tasked
      the Duke Evidence Synthesis Group with creating a prioritized agenda for research
      in this area that would incorporate the perspectives of relevant stakeholders. We
      identified a list of potential evidence gaps by reviewing existing literature and
      engaged a diverse group of 9 stakeholders to expand and refine this list. Using a
      forced-ranking prioritization method, stakeholders prioritized 10 of 23 potential
      evidence gaps as the most pressing for future research. These evidence gaps
      relate to 3 areas: the comparative effectiveness of intervention strategies, the
      effect of antipsychotics on patient-centered outcomes, and the influence of
      various patient characteristics on antipsychotic effectiveness. In addition to
      presenting these findings, we suggest appropriate study designs for addressing
      the stakeholder-prioritized research questions. 

PMID- 24567117
TI  - Ophthalmoplegic migraine: from questions to answers.
AB  - INTRODUCTION: The International Classification of Headache Disorders classifies
      ophthalmoplegic migraine (OM) under "cranial neuralgias and central causes of
      facial pain." OM is diagnosed when all the following criteria are satisfied: A.
      At least two attacks fulfilling criterion B. B. Migraine-like headache
      accompanied or followed within four days of its onset by paresis of one or more
      of the III, IV and/or VI cranial nerves. C. Parasellar orbital fissure and
      posterior fossa lesions ruled out by appropriate investigations. In children the
      syndrome is rare and magnetic resonance (MR) shows strongly enhancing thickened
      nerve at the root entry zone (REZ). METHOD: The authors review the literature
      focusing on pathogenesis theories. RESULTS: The authors suggest that ischemic
      reversible breakdown of the blood-nerve barrier is the most probable cause of OM
      and to include MR findings in the hallmarks of the disease. CONCLUSION: OM is the
      same disease in adulthood and childhood, even if in adults the MR imaging
      findings are negative. In the authors' opinion, OM should be classified as
      migraine.

PMID- 24567118
TI  - Subclinical cerebellar dysfunction in patients with migraine: evidence from
      eyeblink conditioning.
AB  - BACKGROUND: Clinical findings suggest cerebellar dysfunction in patients with
      migraine. Eyeblink classical conditioning (EBCC) is a simple form of associative
      learning which depends on the integrity of the cerebellum. The aim of this study
      was to assess whether EBCC is disturbed in patients with migraine. METHODS: A
      delay conditioning paradigm was used in the headache-free interval in 32 female
      patients with migraine, in 24 of them without (MwoA) and eight with aura (MwA),
      and in 32 age-matched female controls. As primary outcome measure acquisition and
      as secondary outcome measures timing and extinction of conditioned eyeblink
      responses (CR) were assessed. RESULTS: CR acquisition was significantly reduced
      in all migraine patients (mean total CR incidence 35.2 +/- 22.1%) compared to
      controls (54.7 +/- 21.3%; p < 0.001; Bonferroni-corrected p level < 0.025) and in
      MwA patients (19.9 +/- 20.2%) compared to matched controls (58.2 +/- 27.0%; p =
      0.006) but not in MwoA patients (40.3 +/- 20.6%) compared to matched controls
      (53.6 +/- 19.7%; p = 0.028; Bonferroni-corrected p level < 0.0166). Decrease of
      CR incidences in MwA patients was not significantly different compared to MwoA
      patients (p = 0.021; Bonferroni-corrected p level < 0.0166). CR timing and
      extinction was not affected in migraine patients. CONCLUSIONS: Reduced
      acquisition of CRs in the cohort of female patients studied here supports
      findings of a cerebellar dysfunction in migraine.

PMID- 24567120
TI  - A comprehensive functional and clinical analysis of ABCC2 and its impact on
      treatment response to carbamazepine.
AB  - At the blood-brain barrier, overexpression of the drug efflux transporter ABCC2
      (also known as MRP2) has been proposed as a mechanism for impaired carbamazepine
      (CBZ) treatment response in epilepsy. However, investigation of the impact of
      ABCC2 polymorphisms on CBZ treatment efficacy has produced conflicting and
      inconclusive results. A series of in vitro cell efflux and plasma membrane
      vesicle uptake assays were undertaken to investigate whether CBZ was an ABCC2
      substrate. In addition, the effect of three common ABCC2 polymorphisms, -24C>T,
      c.1249G>A and c.3972C>T, on the efficacy of CBZ in epilepsy (assessed using the
      clinical end points time to first seizure and time to 12-month remission from the
      SANAD (Standard and New Antiepileptic Drugs) trial) was determined. CBZ was found
      not to be a substrate for human ABCC2 in vitro. Clinically, no significant
      association was observed for the ABCC2 genetic variants and CBZ treatment
      outcomes. This comprehensive analysis does not support a role for ABCC2 in CBZ
      treatment efficacy. 

PMID- 24567121
TI  - Instant gelation synthesis of 3D porous MoS2@C nanocomposites for lithium ion
      batteries.
AB  - Three-dimensional (3D) nanoporous architectures, possessing high surface area,
      massive pores, and excellent structural stability, are highly desirable for many
      applications including catalysts and electrode materials in lithium ion
      batteries. However, the preparation of such materials remains a major challenge.
      Here, we introduce a novel method, instant gelation, for the synthesis of such
      materials. The as-prepared porous 3D MoS2@C nanocomposites, with layered MoS2
      clusters or strips ingrained in porous and conductive 3D carbon matrix, indeed
      showed excellent electrochemical performance when applied as anode materials for
      lithium ion batteries. Its interconnected carbon network ensures good
      conductivity and fast electron transport; the micro-, and mesoporous nature
      effectively shortens the lithium ion diffusion path and provides room necessary
      for volume expansion. The large specific surface area is beneficial for a better
      contact between electrode materials and electrolyte. 

PMID- 24567122
TI  - Improved expression of recombinant human factor IX by co-expression of GGCX, VKOR
      and furin.
AB  - Recombinant human FIX concentrates (rhFIX) are essential in the treatment and
      prevention of bleeding in the bleeding disorder haemophilia B. However, due to
      the complex nature of FIX production yields are low which leads to high treatment
      costs. Here we report the production of rhFIX with substantially higher yield by
      co-expressing human FIX with GGCX (gamma-glutamyl carboxylase), VKOR (vitamin K
      epoxide reductase) and furin (paired basic amino acid cleaving enzyme) in Chinese
      hamster ovary (CHO) cells. Our results show that controlled co-expression of GGCX
      with FIX is critical to obtain high rhFIX titre, and, that co-expression of VKOR
      further increased the yield of active rhFIX. Furin co-expression improved
      processing of the leader peptide of rhFIX but had a minor effect on yield of
      active rhFIX. The optimal expression level of GGCX was surprisingly low and
      required unusual engineering of expression vector elements. For VKOR and furin
      the control of expression was less critical and could be achieved by standard
      vector element. Using our expression vectors an rhFIX-producing clone with an
      expression level of up to 30 mg/L of active rhFIX was obtained. In addition an
      efficient single step purification method was developed to obtain pure and active
      rhFIX with up to 94% yield.

PMID- 24567119
TI  - Body fluid cytokine levels in mild cognitive impairment and Alzheimer's disease:
      a comparative overview.
AB  - This article gives a comprehensive overview of cytokine and other inflammation
      associated protein levels in plasma, serum and cerebrospinal fluid (CSF) of
      patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI). We
      reviewed 118 research articles published between 1989 and 2013 to compare the
      reported levels of 66 cytokines and other proteins related to regulation and
      signaling in inflammation in the blood or CSF obtained from MCI and AD patients.
      Several cytokines are evidently regulated in (neuro-) inflammatory processes
      associated with neurodegenerative disorders. Others do not display changes in the
      blood or CSF during disease progression. However, many reports on cytokine levels
      in MCI or AD are controversial or inconclusive, particularly those which provide
      data on frequently investigated cytokines like tumor necrosis factor alpha (TNF
      alpha) or interleukin-6 (IL-6). The levels of several cytokines are possible
      indicators of neuroinflammation in AD. Some of them might increase steadily
      during disease progression or temporarily at the time of MCI to AD conversion.
      Furthermore, elevated body fluid cytokine levels may correlate with an increased
      risk of conversion from MCI to AD. Yet, research results are conflicting. To
      overcome interindividual variances and to obtain a more definite description of
      cytokine regulation and function in neurodegeneration, a high degree of
      methodical standardization and patients collective characterization, together
      with longitudinal sampling over years is essential. 

PMID- 24567123
TI  - Modulation of adipose tissue lipolysis and body weight by high-density
      lipoproteins in mice.
AB  - BACKGROUND: Obesity is associated with reduced levels of circulating high-density
      lipoproteins (HDLs) and its major protein, apolipoprotein (apo) A-I. As a result
      of the role of HDL and apoA-I in cellular lipid transport, low HDL and apoA-I may
      contribute directly to establishing or maintaining the obese condition. METHODS:
      To test this, male C57BL/6 wild-type (WT), apoA-I deficient (apoA-I(-/-)) and
      apoA-I transgenic (apoA-I(tg/tg)) mice were fed obesogenic diets (ODs) and
      monitored for several clinical parameters. We also performed cell culture
      studies. RESULTS: ApoA-I(-/-) mice gained significantly more body weight and body
      fat than WT mice over 20 weeks despite their reduced food intake. During a
      caloric restriction regime imposed on OD-fed mice, apoA-I deficiency
      significantly inhibited the loss of body fat as compared with WT mice. Reduced
      body fat loss with caloric restriction in apoA-I(-/-) mice was associated with
      blunted stimulated adipose tissue lipolysis as verified by decreased levels of
      phosphorylated hormone-sensitive lipase (p-HSL) and lipolytic enzyme mRNA. In
      contrast to apoA-I(-/-) mice, apoA-I(tg/tg) mice gained relatively less weight
      than WT mice, consistent with other reports. ApoA-I(tg/tg) mice showed increased
      adipose tissue lipolysis, verified by increased levels of p-HSL and lipolytic
      enzyme mRNA. In cell culture studies, HDL and apoA-I specifically increased
      catecholamine-induced lipolysis possibly through modulating the adipocyte plasma
      membrane cholesterol content. CONCLUSIONS: Thus, apoA-I and HDL contribute to
      modulating body fat content by controlling the extent of lipolysis. ApoA-I and
      HDL are key components of lipid metabolism in adipose tissue and constitute new
      therapeutic targets in obesity.

PMID- 24567124
TI  - Comparative genomics analysis of Lactobacillus species associated with weight
      gain or weight protection.
AB  - BACKGROUND: Some Lactobacillus species are associated with obesity and weight
      gain while others are associated with weight loss. Lactobacillus spp. and
      bifidobacteria represent a major bacterial population of the small intestine
      where lipids and simple carbohydrates are absorbed, particularly in the duodenum
      and jejunum. The objective of this study was to identify Lactobacillus spp.
      proteins involved in carbohydrate and lipid metabolism associated with weight
      modifications. METHODS: We examined a total of 13 complete genomes belonging to
      seven different Lactobacillus spp. previously associated with weight gain or
      weight protection. We combined the data obtained from the Rapid Annotation using
      Subsystem Technology, Batch CD-Search and Gene Ontology to classify gene function
      in each genome. RESULTS: We observed major differences between the two groups of
      genomes. Weight gain-associated Lactobacillus spp. appear to lack enzymes
      involved in the catabolism of fructose, defense against oxidative stress and the
      synthesis of dextrin, L-rhamnose and acetate. Weight protection-associated
      Lactobacillus spp. encoded a significant gene amount of glucose permease.
      Regarding lipid metabolism, thiolases were only encoded in the genome of weight
      gain-associated Lactobacillus spp. In addition, we identified 18 different types
      of bacteriocins in the studied genomes, and weight gain-associated Lactobacillus
      spp. encoded more bacteriocins than weight protection-associated Lactobacillus
      spp. CONCLUSIONS: The results of this study revealed that weight protection
      associated Lactobacillus spp. have developed defense mechanisms for enhanced
      glycolysis and defense against oxidative stress. Weight gain-associated
      Lactobacillus spp. possess a limited ability to breakdown fructose or glucose and
      might reduce ileal brake effects.

PMID- 24567125
TI  - Higher baseline irisin concentrations are associated with greater reductions in
      glycemia and insulinemia after weight loss in obese subjects.
AB  - Irisin is assumed to be a relevant link between muscle and weight maintenance as
      well as to mediate exercise benefits on health. The aim of this study was to
      assess the possible associations between irisin levels and glucose homeostasis in
      obese subjects with metabolic syndrome (MetS) following an energy-restricted
      treatment. Ninety-six adults with excessive body weight and MetS features
      underwent a hypocaloric dietary pattern for 8 weeks, within the RESMENA
      randomized controlled trial (www.clinicaltrials.gov; NCT01087086). After the
      intervention, dietary restriction significantly reduced body weight and evidenced
      a dietary-induced decrease in circulating levels of irisin in parallel with
      improvements on glucose homeostasis markers. Interestingly, participants with
      higher irisin values at baseline (above the median) showed a greater reduction on
      glucose (P=0.022) and insulin (P=0.021) concentrations as well as on the
      homeostasis model assessment index (P=0.008) and triglycerides (P=0.006) after
      the dietary intervention, compared with those presenting low-irisin baseline
      values (below the median). Interestingly, a positive correlation between irisin
      and carbohydrate intake was found at the end of the experimental period. In
      conclusion, irisin appears to be involved in glucose metabolism regulation after
      a dietary-induced weight loss. 

PMID- 24567126
TI  - Can floral display size compensate for Allee effects caused by low population
      abundance and density in Synthyris bullii (Plantaginaceae), a rare species?
AB  - PREMISE OF THE STUDY: Conservation seeks to address the issues of small
      population size, and the reproductive limitations confronting these populations.
      Sparse, small plant populations often suffer Allee effects such as pollinator
      limitation. However, some studies show that plants in sparse populations
      experience reduced resource competition. As a result, these plants may produce
      larger floral displays, which are also predicted to attract pollinators. The
      negative impacts from reduced floral quantity may thus be offset by improved
      floral quality. METHODS: In a 2-yr field study, population abundance and density
      were quantified for 24 populations of Synthyris bullii (Plantaginaceae), a rare
      prairie endemic. In each population, data were collected on inflorescence size,
      fruit/seed set, and seed germination. KEY RESULTS: Inflorescence size had a
      positive relationship with population inflorescence abundance and density. Fruit
      set and germination responded positively to floral quality (i.e., flower
      density). In comparison, seed set showed a positive relationship with only floral
      quantity (i.e., population abundance). CONCLUSIONS: Contrary to our predictions,
      inflorescence size and population size were not inversely related. While
      attractive floral displays in sparse populations potentially compensate in terms
      of fruit set, population abundance nevertheless plays an important role in seed
      set. Because floral quality and quantity differ in their ability to explain
      reproductive outcomes, studies should examine reproduction at several stages,
      otherwise the impacts of population size may be overlooked. Allee effects
      manifesting at a critical stage of reproduction, such as seed production, may act
      as a bottleneck impeding successful recruitment.

PMID- 24567127
TI  - Sexual reproduction of Japanese knotweed (Fallopia japonica s.l.) at its northern
      distribution limit: new evidence of the effect of climate warming on an invasive
      species.
AB  - PREMISE OF THE STUDY: In response to climate warming, plant species may shift
      their distribution northward, but such a process is slow and hard to detect.
      Alternatively, phenological changes (earlier flowering) are expected as first
      adaptations for populations located near their distribution limit. That could be
      the case for the invasive Japanese knotweed (Fallopia japonica s.l., including
      the hybrid Bohemian knotweed F. *bohemica). We hypothesized that climate warming
      now allows the species to produce viable seeds in the northernmost populations.
      METHODS: Seeds were collected along a 550 km long transect in Quebec, Canada, and
      tested for germination. The genetic diversity of a population was determined
      using polymorphic microsatellite markers to verify whether the species is
      actually producing new individuals through sexual reproduction. KEY RESULTS:
      Japanese knotweed produces, in Quebec, a large number of seeds with a high
      germination rate (up to 93%). The geographical limit for viable seed production
      in North America has been extended to Quebec City, about 500 km north of the
      formerly reported limit. Bohemian knotweeds are genetically diverse, while true
      Japanese knotweeds all share a common multilocus genotype. This suggests that
      Bohemian knotweed stands mostly arose from seed, while true Japanese knotweeds
      result only from the propagation of rhizome or stem fragments. CONCLUSIONS: The
      effect of climate change is already palpable on the phenology of invasive plant
      species at their northern distribution limit. Bohemian knotweed, which until
      recently was rare in Quebec, could rapidly spread in the near future with the
      help of an additional diaspore type (seeds).

PMID- 24567129
TI  - Current status and future prospects of drug delivery systems.
AB  - This is an overview of the current drug delivery systems (DDS) starting with
      various routes of drug administration. Various drug formulations are then
      described as well as devices used for drug delivery and targeted drug delivery.
      There has been a considerable increase in the number of new biotechnology-based
      therapeutics. Most of these are proteins and peptides, and their delivery
      presents special challenges. Cell and gene therapies are sophisticated methods of
      delivery of therapeutics. Nanoparticles are considered to be important in
      refining drug delivery; they can be pharmaceuticals as well as diagnostics.
      Refinements in drug delivery will facilitate the development of personalized
      medicine in which targeted drug delivery will play an important role. There is
      discussion about the ideal DDS, commercial aspects, challenges, and future
      prospects. 

PMID- 24567128
TI  - Effect of superoxide dismutase-entrapped liposomes and protein transduction
      domain-superoxide dismutase on human umbilical vein endothelial cells.
AB  - Superoxide dismutases (SOD) are able to remove the superoxide anion free radicals
      produced by environmental stress and thereby protect cells from being injured by
      reactive oxygen species. However, SOD is unable to transduce automatically across
      cell membranes. Protein transduction domains (PTDs) are peptides able to mediate
      protein delivery into cells and were first observed in the HIV-1 Tat protein. In
      the present study, PTD (RKKRRQRRR) was fused to Dunaliella salina (Ds)MnSOD to
      form PTD-DsMnSOD. This was inserted into pET32a to construct the recombinant
      plasmid pET32a-PTD-DsMnSOD and transduced into E. coli BL21(DE3) to obtain
      purified PTD-DsMnSOD proteins. Liposome-encapsulated proteins are also able to
      cross cell membranes. In this study, DsMnSOD proteins were purified and
      encapsulated by liposomes. The obtained MnSOD, PTD-MnSOD and liposome MnSOD were
      used to protect human umbilical vein endothelial cells (HUVECs) from injury under
      oxygen pressure. A cell counting kit 8 was used to test the survival rate of
      HUVECs and results indicated that the protective effect of MnSOD was limited
      compared with that of PTD-MnSOD and liposome MnSOD. Thus, PTD and liposomes
      exhibited improved effects when MnSOD was present in cells.

PMID- 24567130
TI  - A method for screening mitochondrial fusogenic envelopes for use in mitochondrial
      drug delivery.
AB  - Various types of mitochondrial dysfunctions have been implicated in a variety of
      human diseases. This suggests that mitochondria would be promising therapeutic
      drug targets and mitochondrial therapy would be expected to be useful for the
      treatment of various diseases. We have already reported the development of a MITO
      Porter, a liposome-based nano-carrier that delivers its cargo to mitochondria via
      a membrane-fusion mechanism. In our strategy for delivering cargos to
      mitochondria using a MITO-Porter, the carriers must fuse with the organelle
      membrane. Here we report on methodology for screening various types of lipid
      envelopes that have the potential for fusing with a mitochondrial membrane. The
      method involves monitoring the cancellation of fluorescence resonance energy
      transfer (FRET) and evaluating membrane fusion between the carriers and
      mitochondria in living cells by FRET analysis using a spectral imaging
      fluorescent microscopy system.

PMID- 24567131
TI  - Ultrasound-directed, site-specific gene delivery.
AB  - With the implementation of gene therapy looming in the near term, an effective
      delivery system using noninvasive, nonviral-mediated methods appears as an
      attractive option. This novel platform technology uses gas-filled, ultrasound
      directed acoustic microspheres for both diagnostic imaging and therapy and yet
      may provide a key component for future success in the pursuit of single-gene
      replacement therapy. 

PMID- 24567132
TI  - Synthesis of thermoresponsive polymers for drug delivery.
AB  - A protocol for synthesizing thermosensitive copolymers of N-isopropylacrylamide
      (NIPAM) and N-vinylpyrrolidone (VP), cross-linked with N,N'-methylene-bis
      acrylamide (MBA) has been described in this chapter. The copolymers have been
      formed at different concentrations of NIPAM and VP and at two different
      temperatures (70  degrees C and 30  degrees C). The lower critical solution
      temperature (LCST) of the samples has been measured, and the size of the
      particles formed with the highest concentration of NIPAM and lowest concentration
      of VP (MG1 and NG1) has been measured at three different temperatures of 25 
      degrees C, 35  degrees C, and 37  degrees C. Both MG1 and NG1 showed the lowest
      size at 37  degrees C. The MG1 and NG1 samples were further characterized using
      TEM and SEM. The MG1 particles were subsequently used for protein drug delivery,
      using BSA as a model. The release profile showed the best fit with the zero-order
      model. Finally, cytotoxicity studies of the synthesized MG1 and NG1 particles
      were carried out, using in vitro MTT assay, so as to determine the overall
      biocompatibility of the materials.

PMID- 24567133
TI  - Recombinant stem cells as carriers for cancer gene therapy.
AB  - Recent studies have shown the ability of mesenchymal stem cells (MSCs) to migrate
      toward and engraft into the tumor sites, which provides a potential for their use
      as carriers for cancer gene therapy. Here, we describe the strategies of using
      MSCs as carriers for cancer gene therapy using a nonviral transfection method. 

PMID- 24567134
TI  - Microfluidic-based manufacture of siRNA-lipid nanoparticles for therapeutic
      applications.
AB  - A simple, efficient, and scalable manufacturing technique is required for
      developing siRNA-lipid nanoparticles (siRNA-LNP) for therapeutic applications. In
      this chapter we describe a novel microfluidic-based manufacturing process for the
      rapid manufacture of siRNA-LNP, together with protocols for characterizing the
      size, polydispersity, RNA encapsulation efficiency, RNA concentration, and total
      lipid concentration of the resultant nanoparticles. 

PMID- 24567135
TI  - Microneedle-iontophoresis combinations for enhanced transdermal drug delivery.
AB  - It has recently been proposed that the combination of skin barrier impairment
      using microneedles (MNs) coupled with iontophoresis (ITP) may broaden the range
      of drugs suitable for transdermal delivery as well as enabling the rate of
      delivery to be achieved with precise electronic control. However, few reports
      exist on the combination of ITP with in situ drug-loaded polymeric MN delivery
      systems. Our in vitro permeation studies revealed that MN enhances transdermal
      drug delivery. The combination of dissolving MN and ITP did not further enhance
      the extent of delivery of the low molecular weight drug ibuprofen sodium after
      short application periods. However, the extent of peptide/protein delivery was
      significantly enhanced when ITP was used in combination with hydrogel-forming MN
      arrays. As such, hydrogel-forming MN arrays show promise for the electrically
      controlled transdermal delivery of biomacromolecules in a simple, one-step
      approach, though further technical developments will be necessary before patient
      benefit is realized.

PMID- 24567136
TI  - Polymer nanoparticle-based controlled pulmonary drug delivery.
AB  - The development of novel formulations for controlled pulmonary drug delivery
      purposes has gained remarkable interest in medicine. Although nanomedicine
      represents attractive concepts for the treatment of numerous systemic diseases,
      scant information is available on the controlled drug release characteristics of
      colloidal formulations following lung administration, which might be attributed
      to the lack of methods to follow their absorption and distribution behavior in
      the pulmonary environment.In this chapter, we describe the methods of preparation
      and characterization of drug-loaded polymeric nanoparticles prepared from
      biodegradable charge-modified branched polyesters, aerosolization of the
      nanosuspensions using a vibrating-mesh nebulizer, and evaluation of the pulmonary
      pharmacokinetics (i.e., absorption and distribution characteristics) of the
      nanoscale drug delivery vehicles following aerosol delivery to the airspace of an
      isolated lung model. The disclosed methodology may contribute to the design of
      advanced colloids for the treatment of respiratory disorders. 

PMID- 24567138
TI  - Self-assembling peptide-based delivery of therapeutics for myocardial infarction.
AB  - Drug and cell delivery systems could be modulated to serve as instructive
      microenvironments in regenerative medicine. Towards this end, several synthetic
      biomaterials have been developed to mimic the natural extracellular matrix (ECM)
      for therapeutic use. These include synthetic polymers, decellularized ECM, self
      assembling polymers, and cell-responsive hydrogels with varied applications.
      Here, we describe the development of a self-assembling peptide hydrogel and its
      potential use as a cell and growth factor delivery vehicle to the infarcted heart
      in a rodent model of myocardial infarction.

PMID- 24567137
TI  - Antibody labeling with radioiodine and radiometals.
AB  - Antibodies have been conjugated to radionuclides for various in vitro and in vivo
      applications. Radiolabeled antibodies have been used in clinics and research for
      diagnostic applications both in vitro as reagents in bioassays and in vivo as
      imaging agents. Further, radiolabeled antibodies are used as direct therapeutic
      agents for cancer radioimmunotherapy or as tracers for studying the
      pharmacokinetics and biodistribution of therapeutic antibodies. Antibodies are
      labeled with radiohalogens or radiometals, and the choice of candidate
      radionuclides for a given application is dictated by their emission range and
      half-life. The conjugation chemistry for the coupling of MAbs with the
      radiometals requires a chelator, whereas radiohalogens can be incorporated
      directly in the antibody backbone. In this chapter, we describe the commonly used
      methods for radiolabeling and characterizing the antibodies most commonly used
      radiohalogens (125I/131I) and radiometals (177Lu/99mTc).

PMID- 24567139
TI  - Applications of chitosan nanoparticles in drug delivery.
AB  - We have reviewed the binding affinities of several antitumor drugs doxorubicin
      (Dox), N-(trifluoroacetyl) doxorubicin (FDox), tamoxifen (Tam), 4
      hydroxytamoxifen (4-Hydroxytam), and endoxifen (Endox) with chitosan
      nanoparticles of different sizes (chitosan-15, chitosan-100, and chitosan-200 KD)
      in order to evaluate the efficacy of chitosan nanocarriers in drug delivery
      systems. Spectroscopic and molecular modeling studies showed the binding sites
      and the stability of drug-polymer complexes. Drug-chitosan complexation occurred
      via hydrophobic and hydrophilic contacts as well as H-bonding network. Chitosan
      100 KD was the more effective drug carrier than the chitosan-15 and chitosan-200
      KD.

PMID- 24567140
TI  - A method for evaluating nanoparticle transport through the blood-brain barrier in
      vitro.
AB  - Blood-brain barrier (BBB) represents a formidable barrier for many therapeutic
      drugs to enter the brain tissue. The development of new strategies for enhancing
      drug delivery to the brain is of great importance in diagnostics and therapeutics
      of central nervous system (CNS) diseases. In this context, nanoparticles are an
      emerging class of drug delivery systems that can be easily tailored to deliver
      drugs to various compartments of the body, including the brain. To identify,
      characterize, and validate novel nanoparticles applicable to brain delivery, in
      vitro BBB model systems have been developed. In this work, we describe a method
      to screen nanoparticles with variable size and surface functionalization in order
      to define the physicochemical characteristics underlying the design of
      nanoparticles that are able to efficiently cross the BBB. 

PMID- 24567141
TI  - Bacterial systems for gene delivery to systemic tumors.
AB  - Certain bacteria have emerged as biological gene vectors with natural tumor
      specificity, capable of specifically delivering genes or gene products to the
      tumor environment when intravenously (i.v.) administered to rodent models. Here,
      we describe procedures for studying this phenomenon in vitro and in vivo for both
      invasive and noninvasive bacteria suitable for exploitation as tumor-specific
      therapeutic delivery vehicles, due to their ability to replicate specifically
      within tumors and/or mediate bacterial-mediated transfer of plasmid DNA to
      mammalian cells (bactofection).

PMID- 24567142
TI  - Synthesis of a smart nanovehicle for targeting liver.
AB  - A protocol for the synthesis of a smart drug delivery system based on gold
      nanoparticles has been described in this chapter. The synthesized drug delivery
      system has been shown to release the bioactive material in response to an
      intracellular stimulus (glutathione concentration gradient) and hence shown to
      behave in an intelligent manner. Gold nanoparticles have been employed as the
      core material with the surface functionalities of thiolated PEG. PEG owing to its
      non-immunogenicity and non-antigenicity would impart considerable stability and
      longer in vivo circulation time to the gold nanoparticles. The end groups of PEG
      chains have been derivatized with functional groups like aldehyde (-CHO) and
      amine (-NH2) which could behave as flexible arms for the attachment of "target
      specific ligands" and other bioactive substances. Lactose, a liver targeting
      ligand, has been employed as the target specific moiety. A Coumarin derivative
      has been synthesized and used as the model fluorescent tag as well as a linker to
      examine the glutathione-mediated release through fluorescence spectroscopy and
      for the conjugation of bioactive molecules, respectively. A check for the
      cytocompatibility of the synthesized nanovehicle on the cultured mammalian cell
      lines has also been carried out. Finally, in the latter parts of the chapter
      (mimicking the in vivo conditions), time-dependent in vitro release of the model
      fluorescent moiety has also been analyzed at different glutathione
      concentrations.

PMID- 24567143
TI  - Intranasal delivery of chitosan-siRNA nanoparticle formulation to the brain.
AB  - Neurodegeneration is characterized by a progressive loss of neuron structure and
      function. Most neurodegenerative diseases progress slowly over the time. There is
      currently no cure available for any neurodegenerative disease, and the existing
      therapeutic interventions only alleviate the symptoms of the disease. The
      advances in the drug discovery research have come to a halt with a lack of
      effective means to deliver drugs at the targeted site. In addition, the route of
      delivering the drugs is equally important as most invasive techniques lead to
      postoperative complications. This chapter focuses on a non-invasive, intranasal
      mode of therapeutic delivery using nanoparticles, which is currently being
      explored. The intranasal route of delivery is a well-established route to deliver
      drugs via the olfactory and trigeminal neuronal pathways. It is known to be the
      fastest and most effective way to bypass the blood-brain barrier to reach the
      central nervous system. The presented chapter highlights the method of intranasal
      delivery in mice using chitosan-siRNA nanoparticle formulation, under mild
      anesthesia and the identification of successful siRNA delivery in the brain
      tissues, through histology and other well-established laboratory protocols. 

PMID- 24567144
TI  - Intrathecal delivery of analgesics.
AB  - Targeted intrathecal (IT) drug delivery systems (IDDS) are an option in
      algorithms for the treatment of patients with moderate to severe chronic
      refractory pain when more conservative options fail. This therapy is well
      established and supported by several publications. It has shown efficacy and is
      an important tool for the treatment of spasticity, and both cancer and
      nonmalignant pain. Recent technological advances, new therapeutic applications,
      reported complications, and the costs as well as maintenance required for this
      therapy require the need to stay up-to-date about new recommendations that may
      improve outcomes. This chapter reviews all technological issues regarding IDDS
      implantation with follow-up, and pharmacological recommendations published during
      recent years that provide evidence-based decision making process in the
      management of chronic pain and spasticity in patients.

PMID- 24567145
TI  - ALK5 inhibition blocks TGFbeta-induced CCN1 expression in human foreskin
      fibroblasts.
AB  - The potent profibrotic cytokine TGFbeta induces connective tissue growth factor
      (CCN2/CTGF) is induced in fibroblasts in a fashion sensitive to SB-431542, a
      specific pharmacological inhibitor of TGFbeta type I receptor (ALK5). In several
      cell types, TGFbeta induces CCN1 but suppresses CCN3, which opposes CCN1/CCN2
      activities. However, whether SB-431542 alters TGFbeta-induced CCN1 or CCN3 in
      human foreskin fibroblasts in unclear. Here we show that TGFbeta induces CCN1 but
      suppresses CCN3 expression in human foreskin fibroblasts in a SB-431542-sensitive
      fashion. These results emphasize that CCN1/CCN2 and CCN3 are reciprocally
      regulated and support the notion that blocking ALK5 or addition of CCN3 may be
      useful anti-fibrotic approaches. 

PMID- 24567146
TI  - Prioritization of research addressing management strategies for ductal carcinoma
      in situ.
AB  - Ductal carcinoma in situ is a common finding in women having mammography
      screening, and there is considerable uncertainty about the balance of harms and
      benefits of different management options. This article outlines the process for
      developing a prioritized research agenda for the Patient-Centered Outcomes
      Research Institute as informed by a diverse group of stakeholders on the
      management of ductal carcinoma in situ. Evidence gaps were identified by
      reviewing existing literature and engaging diverse stakeholders to refine these
      gaps. Stakeholders ranked evidence gaps by importance from their perspectives
      using a forced-ranking prioritization method. PubMed was searched for relevant
      recent studies, and ClinicalTrials.gov was searched for relevant ongoing trials
      for the 10 highest-ranked evidence gaps. Strengths and limitations of different
      study designs were assessed to address gaps. Stakeholders prioritized evidence
      gaps related to incorporation of patient-centered outcomes into future research,
      development of better methods to predict risk for invasive cancer, evaluation of
      a strategy of active surveillance, and testing of decision-making tools. The
      degree to which prioritized evidence gaps may have already been addressed is
      uncertain because a comprehensive systematic review has not been done. 

PMID- 24567147
TI  - Capturing peripersonal spatial neglect: an electronic method to quantify
      visuospatial processes.
AB  - Computerized as well as paper-and-pencil tasks are applied in mapping
      visuospatial neglect in experimental research and clinical practice. This article
      presents a new kind of computer-based assessment method, using an electronic pen
      display and user-friendly software. The approach is tailored to specific spatial
      processes and highlights the usefulness of a pen display in neglect patients. The
      advantages of the introduced method are illustrated by a recently designed
      battery of classic, as well as new, types of tests. The development of the
      appropriate stimuli and the assorted scoring systems is addressed, as well as the
      resulting types of task implementation and data generation. The diagnostic value
      of the different visuospatial neglect tests is demonstrated by comparative
      analyses between a neglect group and a control group. Among the benefits of the
      proposed assessment method are (1) the opportunity to perform standardized
      repeated measurements to quantify recovery, (2) online performance monitoring,
      (3) flexible employment, (4) the collection of exact data over a short period,
      and (5) the easy availability of more refined quantitative as well as interesting
      qualitative information, especially as compared to classic or paper-and-pencil
      tasks. To indicate that this method also lends itself well to measures for
      treatment procedures, an illustration is given with respect to specific
      measurements during prism adaptation. The tasks of the Visuospatial Neglect Test
      Battery and the prism adaptation measures are illustrated by a case study. The
      outlined applications are discussed with respect to experimental as well as
      clinical purposes. 

PMID- 24567148
TI  - Short answer question case series: ventilatory considerations in a patient with
      morbid headache.

PMID- 24567149
TI  - Top 10 mobile apps in emergency medicine.
AB  - Mobile apps are increasingly being used at the bedside as a part of clinical
      care. With almost 300 emergency medicine-related apps available in the Apple App
      Store, it can be overwhelming deciding which are most useful for emergency
      department providers. A Top 10 list of apps is highlighted which illustrate the
      many ways that quality apps can positively impact the care of emergency
      department patients.

PMID- 24567150
TI  - Mechanistic insights into mode of actions of novel oligopeptidase B inhibitors
      for combating leishmaniasis.
AB  - Leishmaniasis is an endemic disease caused by infection with one of several
      different species of protozoan parasite Leishmania. Oligopeptidase B (OPB) is a
      serine peptidase which plays a vital role in survival of the Leishmania parasite
      in the host (human) macrophage and help in attaining complete virulence.
      Inhibition of this peptidase would check the parasite growth inside the host
      organism and would thus control its infection. Lack of efficient and cheap drugs
      has led to an urgent need for development of new anti-leishmanial drugs and this
      study is a step forward in this direction. Using a structure-based approach we
      virtually screened a large naturally-occurring compound library against OPB and
      subjected two top scoring compounds with high binding affinity to molecular
      dynamics simulations which showed a stable RMSD trajectory. The first compound
      COP (Glide score: -13.183) was found stable for 15 ns at RMSD of 2.5 A while the
      second compound TOA (Glide score: -10.308) was stable for 8 ns at RMSD of 1.5 A.
      The screened compounds interacted with some crucial residues of OPB such as COP
      interacted with Ser577 and His697 (part of the catalytic triad), Tyr499
      (responsible for substrate stability), Arg576 (conserved in protozoan family) and
      Arg664 (plays a role in stabilization of the bound inhibitor). TOA also
      interacted with Glu669 (conserved in protozoan family) in addition to the
      residues interacted with COA. These interactions are crucial for OPB inhibition.
      This study identified naturally-occurring compound leads against OPB with good
      binding affinity and low toxicity to human cells. 

PMID- 24567152
TI  - The influence of anharmonic and solvent effects on the theoretical vibrational
      spectra of the guanine-cytosine base pairs in Watson-Crick and Hoogsteen
      configurations.
AB  - The theoretical IR and Raman spectra of the guanine-cytosine DNA base pairs in
      Watson-Crick and Hoogsteen configurations were computed using DFT method with M06
      2X meta-hybrid GGA exchange-correlation functional, including the anharmonic
      corrections and solvent effects. The results for harmonic frequencies and their
      anharmonic corrections were compared with our previously calculated values
      obtained with the B3PW91 hybrid GGA functional. Significant differences were
      obtained for the anharmonic corrections calculated with the two different DFT
      functionals, especially for the stretching modes, while the corresponding
      harmonic frequencies did not differ considerable. For the Hoogtseen case the H+
      vibration between the G-C base pair can be characterized as an asymmetric Duffing
      oscillator and therefore unrealistic anharmonic corrections for normal modes
      where this proton vibration is involved have been obtained. The spectral
      modification due to the anharmonic corrections, solvent effects and the influence
      of sugar-phosphate group for the Watson-Crick and Hoogsteen base pair
      configurations, respectively, were also discussed. For the Watson-Crick case also
      the influence of the stacking interaction on the theoretical IR and Raman spectra
      was analyzed. Including the anharmonic correction in our normal mode analysis is
      essential if one wants to obtain correct assignments of the theoretical frequency
      values as compared with the experimental spectra.

PMID- 24567151
TI  - Targeted studies on the interaction of nicotine and morin molecules with amyloid
      beta-protein.
AB  - Alzheimer's disease (AD) is a neurodegenerative disorder that occurs due to
      progressive deposition of amyloid beta-protein (Abeta) in the brain. Stable
      conformations of solvated Abeta1-42 protein were predicted by molecular dynamics
      (MD) simulation using the OPLSAA force field. The seven residue peptide (Lys-Leu
      Val-Phe-Phe-Ala-Glu) Abeta16-22 associated with AD was studied and reported in
      this paper. Since effective therapeutic agents have not yet been studied in
      detail, attention has focused on the use of natural products as effective anti
      aggregation compounds, targeting the Abeta1-42 protein directly. Experimental and
      theoretical investigation suggests that some compounds extracted from natural
      products might be useful, but detailed insights into the mechanism by which they
      might act remains elusive. The molecules nicotine and morin are found in
      cigarettes and beverages. Here, we report the results of interaction studies of
      these compounds at each hydrophobic residue of Abeta16-22 peptide using the
      hybrid ONIOM (B3LYP/6-31G**:UFF) method. It was found that interaction with
      nicotine produced higher deformation in the Abeta16-22 peptide than interaction
      with morin. MD simulation studies revealed that interaction of the nicotine
      molecule with the beta-sheet of Abeta16-22 peptide transforms the beta-sheet to
      an alpha-helical structure, which helps prohibit the aggregation of Abeta
      protein.

PMID- 24567153
TI  - ReaxFF molecular dynamics simulations of the initial pyrolysis mechanism of
      unsaturated triglyceride.
AB  - To understand the impact of C = C double bonds in acyl chains of unsaturated
      triglycerides on the reaction mechanism and product composition in their initial
      pyrolysis process, ReaxFF molecular dynamics simulations were carried out using a
      molecular model, trilinolenin, at temperatures of 2000, 2250, and 2500 K.
      Analyses indicated that the observed pyrolysis mechanisms of unsaturated
      triglyceride are nearly identical to the saturated triglyceride, and the
      pyrolysis products also include alkanes, alkenes, alkadienes, aromatics,
      oxygenated species, CO2, and H2. The formation of intermediates and products is a
      sequential process. Three C--O bonds in trilinolenin molecule are usually
      successive dissociated first, leading to the formation of unsaturated C3H5.
      radical and straight-chain C18H29O2. (RCOO.) radicals. Following that, the
      deoxygenated alkenyl chain is produced through decarboxylation of RCOO . radicals
      with consequent release of CO2. The resulting hydrocarbon radicals undergo a
      variety of disproportionation, isomerization, and hydrogen-transfer reactions,
      yielding straight and branched-chain hydrocarbons. It was found that the scission
      of C--O bond and decarboxylation should preferentially occur before the cleavage
      of the C--C bond beta to the C = C bond in the initial decomposition process of
      unsaturated trilinolenin. In addition, the formation of cyclic hydrocarbons could
      proceed through intramolecular cyclization mechanisms, including non-radical
      electrocyclic, biradical cyclization and cyclization of alkenyl radical, which
      are inconsistent with previously proposed bimolecular Diels-Alder addition
      mechanisms. More rapid pyrolysis of trilinolenin would occur at higher
      temperatures without significantly affecting the apparent reaction mechanisms of
      trilinolenin pyrolysis in the considered temperature range. Aromatic ring
      structures are observed to be stable after formation and do not decay within the
      500 ps simulation period.

PMID- 24567154
TI  - A theoretical study on ascorbic acid dissociation in water clusters.
AB  - Dissociation of ascorbic acid in water has been studied by using a cluster model.
      It was examined by density functional theory (DFT) with the V3LYP, M06, and
      wB97XD functionals and a 6-311++G(d,p) basis set. The thermodynamic and kinetic
      characteristics of proton transfer from ascorbic acid molecule to water clusters
      were calculated as well as the equilibrium constants (pK a ) for the related
      processes. The used functionals in the DFT method together with continuum solvent
      models provided results close to the experimental data for the dissociation
      constant of ascorbic acid in aqueous solution. 

PMID- 24567155
TI  - Quantum chemical DFT study of the interaction between molecular oxygen and FeN4
      complexes, and effect of the macrocyclic ligand.
AB  - Density functional theory (DFT) was used to examine the interaction between
      molecular oxygen (O2) and macrocyclic iron complexes of the type FeN4 during the
      formation of FeN4--O2 adducts. In order to understand how this interaction is
      affected by different macrocyclic ligands, O2 was bonded to iron
      tetraaza[14]annulene (FeTAA), iron-tetramethyl-tetraaza[14]annulene (FeTMTAA),
      iron-hexamethyl-tetraaza[14]annulene (FeHMTAA), iron dibenzotetraaza[14]annulene
      (FeDBTAA), and two iron-tetramethyl-dibenzotetraaza[14]annulene complexes
      (FeTMDBTAA1, FeTMDBTAA2). The ground state for FeN4-O2 adducts was the open-shell
      singlet. Analysis of the factors influencing the O2 bonding process showed that
      different macrocyclic ligands yielded adducts with differences in O--O and Fe--O2
      bond lengths, total charge over the O2 fragment, O--O vibrational frequency, and
      spin density in the O2 fragment. A smaller energy gap between the alpha-HOMO of
      the FeN4 complexes and the beta-LUMO of O2 increased the interaction between the
      complex and the O2 molecule. The order of activity was FeDBTAA < FeTMDBTAA2 <
      FeTMDBTAA1 < FeTAA < FeTMTAA < FeHMTAA.

PMID- 24567156
TI  - Encapsulation of alkyl and aryl derivatives of quaternary ammonium cations within
      cucurbit[n]uril (n = 6,7) and their inverted diastereomers: density functional
      investigations.
AB  - Electronic structure, vibrational frequencies, and 1H chemical shifts of
      inclusion complexes between CB[n] (n = 6,7) or their inverted iCB[n] diastereomer
      hosts and quaternary diammonium viz., 1,6-hexyldiammonium (HDA) or p
      xylyldiammonium (XYL) cationic guests are obtained from the density functional
      calculations. The interaction of CB[n] or iCB[n] with HDA (guest) conduce
      inclusion complexes in which the guest attains gauche conformation within the
      host cavity. The lowest energy XYL complexes of CB[6] or iCB[6] are comprised of
      one ammonium group orienting parallel to aromatic ring. The CB[7] or iCB[7]
      complexes of XYL on the other hand, reveal ammonium group(s) perpendicular to
      aromatic ring of the guest. The ureido C=O and N--H stretching vibrations on
      complexation engender frequency down-shift in the calculated spectra. This can be
      attributed to C--H-- --O and N--H-- --O interactions in the complex. The
      inverting of glycouril unit in iCB[n] renders a frequency shift (12 cm-1) for the
      C=O stretching in the opposite direction. Molecular electron density topography
      and natural bond orbital analyses have been used to explain the direction of
      frequency shifts. Calculated 1H NMR reveal that guest protons within the host
      cavity not participating in hydrogen bonding interactions, exhibit shielded
      signals compared to isolated XYL or HDA. Likewise the inverted protons in the
      iCB[6]-XYL complex led to up-field signals in calculated 1H NMR as a result of C
      H-- -pi interactions.

PMID- 24567157
TI  - Effect of protonation and hydrogen bonding on 2, 4, 6-substituted pyrimidine and
      its salt complex-experimental and theoretical evidence.
AB  - Quantum molecular simulations of chemical systems can provide detailed
      information that is often inaccessible to direct experimental measurement.
      Pyrimidine is an interesting pi-electron heterocyclic aromatic system which acts
      as the building block of many nucleic acid bases. The hydrogen bonds associated
      with the 2, 4, and 6-substituted pyrimidine and its hydrogen sulfate anion are
      considered for this current work. The experimental and computational evidence for
      the strength of these intra and intermolecular hydrogen are determined using
      vibrational spectra and quantum chemical calculations. Thus the effect of
      hydrogen bonding on the title compound is studied using its geometrical
      parameters, interaction energies, and vibrational spectra. Aromaticity and charge
      transfer studies have been performed to ascertain the aromatic behavior of the
      molecule. The PES scan studies have been done by varying the bond length to
      ascertain the protonation process of the compound. The IR spectral red shift
      (~100 cm-1), blue shift (~97 cm-1) and broadening of the polar stretching peaks
      shows the inter and intramolecular hydrogen bonding strength. Bond length
      alternation of proton donors along with the enormous interaction energies (~0.5
      150 kJ mol-1) between the lone pair and proton donors provides clear evidence for
      this hydrogen bonding. The charge transfer due to the methyl substitutions which
      enhances the possibility of hydrogen bonding has been discussed. The main scope
      of this work is to study the protonation and hydrogen bonding associated with
      charge transfer which has great effect on the 2-amino-4, 6-dimethyl pyrimidinium
      hydrogen sulfate (ADHS) molecule.

PMID- 24567158
TI  - 3D-dynamic representation of DNA sequences.
AB  - A new 3D graphical representation of DNA sequences is introduced. This
      representation is called 3D-dynamic representation. It is a generalization of the
      2D-dynamic dynamic representation. The sequences are represented by sets of
      "material points" in the 3D space. The resulting 3D-dynamic graphs are treated as
      rigid bodies. The descriptors characterizing the graphs are analogous to the ones
      used in the classical dynamics. The classification diagrams derived from this
      representation are presented and discussed. Due to the third dimension, "the
      history of the graph" can be recognized graphically because the 3D-dynamic graph
      does not overlap with itself. Specific parts of the graphs correspond to specific
      parts of the sequence. This feature is essential for graphical comparisons of the
      sequences. Numerically, both 2D and 3D approaches are of high quality. In
      particular, a difference in a single base between two sequences can be identified
      and correctly described (one can identify which base) by both 2D and 3D methods. 

PMID- 24567159
TI  - Small cobalt clusters encapsulated inside Si30C30 nanocages: electronic and
      magnetic properties.
AB  - We investigated the structural, electronic, and magnetic properties of small
      Co(n) clusters (n = 2-6) when they were endohedrally doped into Si30C30 nanocages
      using ab initio calculations based on density functional theory. Two different
      spin-polarized functionals based on the generalized gradient and local density
      approximations were used to characterize Co(n)@Si30C30. It was found that the
      Co(n) clusters encapsulated inside Si30C30 nanocages can form stable structures
      due to their significant binding energies. Among the various encapsulated
      clusters studied, the Co4 cluster was the most stable in a Si30C30 nanocage. We
      also found that the magnetic moments of the clusters decreased during the
      encapsulation process due to substantial hybridization between the cobalt cluster
      and the Si30C30 nanocage structure, although the encaged Co2 cluster presented
      somewhat different behavior. It was found that significant magnetic moments are
      induced in the wall of the nanocage, and that Co(n)@Si30C30 presents higher total
      magnetic moments than Co(n)@C60.

PMID- 24567160
TI  - Theoretical study of absorption of 2,2,6,6-tetramethylpiperidine-1-oxoammonium
      cation (TEMPO) on TiO2(110) rutile surface.
AB  - We present a theoretical study of the adsorption of 2,2,6,6-tetramethylpiperidine
      1-oxoammonium cation (TEMPO) onto the TiO2(110) surface rutile, investigating its
      bonding nature, electron properties and structural stability. Based on the
      results obtained with the PBE0/def2-SVP method, natural bond orbital (NBO)
      analysis suggests a bond order for the O--O bond in complexes 5 and 6, of 0.25
      and 0.88, respectively. We also described NBOs for the main interactions of the
      TiO2-TEMPO complexes.

PMID- 24567161
TI  - Theoretical study of the solvent effect on the aromaticity of benzene: a NICS
      analysis.
AB  - Nucleus-independent chemical shift (NICS) quantities for benzene-benzene and
      benzene-water species were obtained and are discussed in gas phase and in
      solution. Besides standard polarizable continuum model (PCM) calculations,
      sequential Monte Carlo/quantum mechanics (S-MC/QM) were also performed. Benzene
      was shown to be slightly more aromatic in condensate phase when we considered the
      average solvent configuration (ASEC) approach with explicit molecules. 

PMID- 24567162
TI  - Homology modeling, molecular dynamics and atomic level interaction study of snake
      venom 5' nucleotidase.
AB  - 5' Nucleotidase (5' NUC) is a ubiquitously distributed enzyme known to be present
      in snake venoms (SV) that is responsible primarily for causing dysregulation of
      physiological homeostasis in humans by inducing anticoagulant effects and by
      inhibiting platelet aggregation. It is also known to act synergistically with
      other toxins to exert a more pronounced anti-coagulant effect during
      envenomation. Its structural and functional role is not yet ascertained clearly.
      The 3D structure of snake venom 5' nucleotidase (SV-5' NUC) is not yet known and
      was predicted by us for the first time using a comparative homology modeling
      approach using Demansia vestigiata protein sequence. The accuracy and stability
      of the predicted SV-5' NUC structure were validated using several computational
      approaches. Key interactions of SV-5' NUC were studied using experimental
      studies/molecular docking analysis of the inhibitors vanillin, vanillic acid and
      maltol. All these inhibitors were found to dock favorably following
      pharmacologically relevant absorption, distribution, metabolism and excretion
      (ADME) profiles. Further, atomic level docking interaction studies using
      inhibitors of the SV-5' NUC active site revealed amino acid residues Y65 and T72
      as important for inhibitor-(SV-5' NUC) interactions. Our in silico analysis is in
      good agreement with experimental inhibition results of SV-5' NUC with vanillin,
      vanillic acid and maltol. The present study should therefore play a guiding role
      in the experimental design of new SV-5' NUC inhibitors for snake bite management.
      We also identified a few pharmacophoric features essential for SV-5' NUC
      inhibitory activity that can be utilized further for the discovery of putative
      anti-venom agents of therapeutic value for snake bite management. 

PMID- 24567163
TI  - Scytonin, a novel cyanobacterial photoprotective pigment: calculations of Raman
      spectroscopic biosignatures.
AB  - The Raman spectrum of scytonin, a novel derivative of the parent scytonemin, is
      predicted from DFT calculations of the most stable, lowest energy, conformational
      structure. The diagnostic importance of this study relates to the spectral
      ability to discriminate between scytonemin and its derivatives alone or in
      admixture with geological matrices from identified characteristic Raman spectral
      signatures. The successful interpretation of biosignatures from a wide range of
      cyanobacterial extremophilic colonization in terrestrial and extraterrestrial
      scenarios is a fundamental requirement of the evaluation of robotic spectroscopic
      instrumentation in search for life missions. Scytonemin is produced exclusively
      by cyanobacterial colonies in environmentally stressed habitats and is widely
      recognized as a key target biomarker molecule in this enterprise. Here, the
      detailed theoretical analysis of the structure of scytonin enables a protocol to
      be established for the recognition of characteristic bands in its Raman spectrum
      and to accomplish the successful differentiation between scytonin and scytonemin
      as well as other scytonemin derivatives such as the dimethoxy and tetramethoxy
      compounds that have been isolated from cyanobacterial colonies but which have not
      yet been characterized spectroscopically. The results of this study will
      facilitate an extension of the database capability for miniaturized Raman
      spectrometers which will be carried on board search for life robotic missions to
      Mars, Europa, and Titan. 

PMID- 24567164
TI  - Peanut-like MnO@C core-shell composites as anode electrodes for high-performance
      lithium ion batteries.
AB  - Peanut-like MnO@C core-shell composites with an internal carbon network (P-MnO@C)
      were prepared via an in situ synchronous graphitization and reduction process.
      These P-MnO@C composites exhibit high specific capacity and rate capability, good
      stability and excellent long-term cycling life for application in lithium ion
      batteries. 

PMID- 24567165
TI  - Cross-gender social normative effects for violence in middle school: do girls
      carry a social multiplier effect for at-risk boys?
AB  - A social multiplier effect is a social interaction in which the behavior of a
      person in a social network varies with the normative behavior of others in the
      network, also known as an endogenous interaction. Policies and intervention
      efforts can harness social multiplier effects because, in theory, interventions
      on a subset of individuals will have "spillover effects" on other individuals in
      the network. This study investigates potential social multiplier effects for
      violence in middle schools, and whether there is evidence for a social multiplier
      effect transmitted from girls to boys. Three years of longitudinal data (2003
      2005) from Project Northland Chicago were used to investigate this question, with
      a sample consisting of youth in Grades 6 through 8 in 61 Chicago Public Schools
      (N = 4,233 at Grade 6, N = 3,771 at Grade 7, and N = 3,793 at Grade 8). The
      sample was 49.3% female, and primarily African American (41.9%) and Latino/a
      (28.7%), with smaller proportions of whites (12.9%), Asians (5.2%) and other
      ethnicities. Results from two sets of regression models estimating the effects of
      20th (low), 50th (average), and 80th (high) percentile scores for girls and boys
      on levels of violence in each gender group revealed evidence for social
      multiplier effects. Specifically, boys and girls were both influenced by social
      multiplier effects within their own gender group, and boys were also affected by
      normative violence scores among girls, typically those of the best-behaved (20th
      percentile) girls. The finding that girls may have positive social influence on
      boys' levels of violent behavior extends prior findings of beneficial social
      effects of girls on boys in the domains of education and risky driving. Further,
      this social normative effect presents a potential opportunity to improve school
      based intervention efforts for reducing violence among youth by leveraging girls
      as carriers of a social multiplier effect for reduced violence in the middle
      school environmental context, particularly among boys, who are at greater risk.

PMID- 24567167
TI  - A longitudinal study of risk factors for repeated sexual coercion and assault in
      U.S. College men.
AB  - The purpose of the current study was to understand the prevalence, severity, and
      predictors of repeated sexual coercion and assault (SCA) in a non-criminal
      sample. Participants were 795 college men who were surveyed at the end of each of
      their 4 years in college. Participants completed self-report inventories once per
      year for 4 years. Measures assessed demographics, adverse childhood experiences,
      offense characteristics, antisocial personality characteristics, attitudes
      towards women and forced sex, perceived social norms, sexual behavior, and
      substance use. Results indicated that, among the 238 participants who reported at
      least once incident of SCA, 68 % engaged in repeated SCA, with repeat offenders
      engaging in aggressive acts of higher severity that began at an earlier age. A
      multinomial logistic regression model compared single and repeat offenders to non
      perpetrators. Both single and repeat offenders endorsed more risky behaviors and
      sexually aggressive beliefs than non-perpetrators. Single offenders were higher
      on childhood adversity than non-perpetrators and repeat offenders were higher on
      antisocial personality traits than non-perpetrators. A second multivariate model
      compared single offenders to repeat offenders. Repeat offenders scored higher
      than single offenders on risky behaviors, sexually aggressive beliefs, and
      antisocial traits. Findings highlight the high prevalence of repeated SCA in
      young adults, the need for interventions that decrease rape supportive attitudes
      and risky substance use, and the importance of expanding models of sexual
      recidivism to include multiple risk factors. 

PMID- 24567166
TI  - At-risk depressive symptoms and alcohol use trajectories in adolescence: a person
      centred analysis of co-occurrence.
AB  - Long-term longitudinal studies that examine whether there are distinct
      trajectories of at-risk depressive symptoms and alcohol use across the high
      school years (e.g., high co-occurrence) are rare in normative samples of
      adolescent boys and girls; yet, this assessment is of critical importance for
      developing effective prevention and intervention strategies. Moreover, the role
      of self-regulation and novelty-seeking behavior in differentiating among distinct
      subgroups of adolescents is not clear. To address these gaps, the present study
      sought to identify subgroups of adolescent boys and girls that indicated at-risk
      trajectories across the high school years for both depressive symptoms and
      alcohol use, and examined the role of delay of gratification and novelty seeking
      at baseline in differentiating among the subgroups. Canadian adolescents (N =
      4,412; 49 % female) were surveyed at four time points (grades 9, 10, 11, and 12).
      Parallel process latent class growth analyses revealed four distinct subgroups
      for both boys and girls, encompassing high co-occurrence, depressive symptoms
      only, alcohol use only, and low co-occurrence. Across gender, delay of
      gratification at baseline differentiated among the four subgroups, with the High
      Co-Occurrence Group group scoring the lowest and the Low Co-Occurrence Group the
      highest. Lower novelty-seeking scores at baseline were associated more with being
      in the Depressive Symptoms Only Group relative to the other groups, particularly
      the Alcohol Use Only Group for boys. Thus, delay of gratification and novelty
      seeking may be useful in identifying youth at risk for co-occurring depressive
      symptoms and alcohol use trajectories, as well as at-risk trajectories for only
      one of these behaviors.

PMID- 24567168
TI  - Click-evoked otoacoustic emissions in children and adolescents with gender
      identity disorder.
AB  - Click-evoked otoacoustic emissions (CEOAEs) are echo-like sounds that are
      produced by the inner ear in response to click-stimuli. CEOAEs generally have a
      higher amplitude in women compared to men and neonates already show a similar sex
      difference in CEOAEs. Weaker responses in males are proposed to originate from
      elevated levels of testosterone during perinatal sexual differentiation.
      Therefore, CEOAEs may be used as a retrospective indicator of someone's perinatal
      androgen environment. Individuals diagnosed with Gender Identity Disorder (GID),
      according to DSM-IV-TR, are characterized by a strong identification with the
      other gender and discomfort about their natal sex. Although the etiology of GID
      is far from established, it is hypothesized that atypical levels of sex steroids
      during a critical period of sexual differentiation of the brain might play a
      role. In the present study, we compared CEOAEs in treatment-naive children and
      adolescents with early-onset GID (24 natal boys, 23 natal girls) and control
      subjects (65 boys, 62 girls). We replicated the sex difference in CEOAE response
      amplitude in the control group. This sex difference, however, was not present in
      the GID groups. Boys with GID showed stronger, more female-typical CEOAEs whereas
      girls with GID did not differ in emission strength compared to control girls.
      Based on the assumption that CEOAE amplitude can be seen as an index of relative
      androgen exposure, our results provide some evidence for the idea that boys with
      GID may have been exposed to lower amounts of androgen during early development
      in comparison to control boys. 

PMID- 24567170
TI  - "Vein involvement during pancreaticoduodenectomy: is there a need for
      redefinition of borderline resectable disease": a commentary on the article
      published by Kelly et al. In the Journal of Gastrointestinal Surgery 17:1209
      (2013).

PMID- 24567169
TI  - Optimization of an amplification protocol for misfolded proteins by using relaxed
      control.
AB  - We investigate an optimal control problem which arises in the optimization of an
      amplification technique for misfolded proteins. The improvement of this technique
      may play a role in the detection of prion diseases. The model consists in a
      linear system of differential equations with a nonlinear control. The appearance
      of oscillations in the numerical simulations is understood by using the Perron
      and Floquet eigenvalue theory for nonnegative irreducible matrices. Then to
      overcome the unsolvability of the optimal control, we relax the problem. In the
      two dimensional case, we solve explicitly the optimal relaxed control problem
      when the final time is large enough. 

PMID- 24567171
TI  - Omental flap for hepatic artery coverage during liver transplantation.
AB  - In 1994, a technique of omental flap interposition to cover the celiac and
      mesenteric vessels after pancreaticoduodenectomy was described. It aimed to
      isolate the pancreatic anastomosis from the vessels dissected during
      pancreaticoduodenectomy. In liver transplantation (LT), the omental flap was
      initially used to reduce the risk of hepatic artery (HA) kinking. Currently, we
      use this technique to cover the dissected HA, reducing the consequences of
      postoperative biliary fistula (BF), particularly the risk of postoperative
      complications (thrombosis/bleeding). We describe this technique adding a simple
      modification consisting of covering the HA with an omental flap after completion
      of the biliary anastomosis. We performed LT with an omental flap to cover the HA
      vessels in 62 (55 %) of the 112 consecutive patients who underwent LT between
      January 2012 and July 2013. No postoperative deaths occurred. The rate of BF was
      9.7 % (six cases). In the omental flap series, no postoperative thrombosis, HA
      pseudoaneurysm, or complications occurred. In the six cases of BF, the dissected
      HAs were completely isolated from the biloma. This simple technique has no
      specific morbidity; it isolates the HA from the biliary anastomosis and therefore
      may reduce the risk of severe postoperative HA complications after LT.

PMID- 24567172
TI  - Comparative effects of chlorhexidine and essential oils containing mouth rinse on
      stem cells cultured on a titanium surface.
AB  - Chlorhexidine (CHX) and Listerine (LIS), an essential oil compound, are the two
      commonly used adjunctive agents for mechanical debridement, for reducing the
      bacterial load in the treatment of peri-implant inflammation. However,
      antimicrobial agents have been reported to be cytotoxic to the alveolar bone
      cells and gingival epithelial cells. The present study was performed to examine
      the effects of antiseptics CHX and LIS, on the morphology and proliferation of
      stem cells. Stem cells derived from the buccal fat pad were grown on machined
      titanium discs. Each disc was immersed in CHX or LIS for 30 sec, 1.5 min or 4.5
      min. Cell morphology was evaluated with a confocal laser microscope and the
      viability of the cells was quantitatively analyzed with the cell counting kit-8
      (CCK-8). The untreated cells attached to the titanium discs demonstrated well
      organized actin cytoskeletons. No marked alterations in the cytoskeletal
      organization were observed in any of the treated groups. The treatment with CHX
      and LIS of the titanium discs decreased the viability of the cells grown on the
      treated discs (P<0.05). The stem cells derived from the buccal fat pad were
      sensitive to CHX and LIS, and a reduction in cellular viability was observed when
      these agents were applied to the discs for 30 sec. Further studies are required
      to determine the optimal application time and concentration of this antimicrobial
      agent for maximizing the reduction of the bacterial load and minimizing the
      cytotoxicity to the surrounding cells.

PMID- 24567173
TI  - Dietary flavonoid and proanthocyanidin intakes and prostate cancer risk in a
      prospective cohort of US men.
AB  - Higher dietary intakes of flavonoids and proanthocyanidins have been associated
      with a lower risk of several cancers. Few prospective epidemiologic studies have
      examined individual flavonoids and proanthocyanidins in relation to prostate
      cancer. We examined these associations in a prospective US cohort of 43,268 men
      with a mean age of 70 years who completed detailed self-administered
      questionnaires in 1999-2000. During a mean follow-up of 7.8 years, 3,974 total
      prostate cancers, including 567 high-grade cases and 362 advanced cases, were
      ascertained. Cox proportional hazards regression models were used to calculate
      multivariable-adjusted relative risks and 95% confidence intervals. Residual
      energy-adjusted total flavonoids (for fifth quintile vs. first quintile, relative
      risk = 1.11, 95% confidence interval: 1.01, 1.23; P for trend = 0.02) and several
      subclasses were positively associated with overall prostate cancer risk, mostly
      limited to the top quintile and the first 2 years of follow-up. The associations
      for total flavonoids, flavan-3-ols, and proanthocyanidins with high-grade
      prostate cancer risk varied by follow-up time. During follow-up from 2002 to
      2009, we observed suggestive inverse trends with higher total flavonoids (P for
      trend = 0.05) and proanthocyanidins (P for trend = 0.04) with high-grade prostate
      cancer, but not with advanced prostate cancer. Although evidence is limited, a
      possible role of total flavonoids and proanthocyanidins in prostate cancer tumor
      progression deserves further study. 

PMID- 24567174
TI  - Wolff-Parkinson-White syndrome in congenital rubella syndrome.

PMID- 24567175
TI  - Summaries for patients. Vitamin, mineral, and multivitamin supplements to prevent
      cardiovascular disease and cancer: recommendations from the U.S. Preventive
      Services Task Force.

PMID- 24567176
TI  - [Acute and overuse injuries of the shoulder in sports].
AB  - BACKGROUND: During sports the shoulder complex is exposed to considerable load
      especially where throwing is important and various pathological changes can
      occur. In the last two decades the shoulder in athletes has become a special term
      in clinical sports medicine METHODS: Selective literature review in PubMed and
      consideration of personal experience, research results as well as national and
      international recommendations RESULTS: In general acute lesions of the shoulder
      caused by sudden sport injuries, such as traumatic luxation, acromioclavicular
      (AC) joint disruption, traumatic tendon ruptures, labral lesions, cartilage
      defects and fractures have to be distinguished from chronic or long-standing
      pathologies due to recurrent microtrauma, such as overuse bursitis and
      tendinitis, as well as secondary forms of impingement along with rotator cuff
      tears and labral lesions. Besides common pathological changes that can be
      observed in almost all overhead-sports, there are also injuries that are more
      sport-specific due to the particular load profile in each sport. These injuries
      are especially common in racquet and throwing sports (e.g. golf, tennis, handball
      and volleyball) as well as in individual and artistic sports (e.g. swimming,
      gymnastics, dancing and rowing), contact and extreme sports (e.g. judo, mixed
      martial arts, bodybuilding, weightlifting, motocross and downhill mountain
      biking). CONCLUSION: Knowledge about sport-specific load profiles as well as
      about the variety of treatment options is crucial for successful treatment of
      these injuries.

PMID- 24567177
TI  - Evaluation of antioxidative/oxidative status and prolidase parameters in cases of
      inguinal hernia with joint hypermobility syndrome.
AB  - PURPOSE: Most previous reports have shown that the basic mechanism of inguinal
      hernia involves insufficient collagen strength and metabolism. The aim of this
      study was to evaluate whether joint hypermobility is involved in the development
      of inguinal hernia in children and to investigate oxidative stress parameters and
      prolidase activity in tissue samples from children with inguinal hernia. METHODS:
      This cross-sectional study involving 41 patients (age, 6.36 +/- 2.96 years) with
      inguinal hernia treated in the pediatric surgery department of our institution
      and 40 age- and sex-matched controls (age, 6.02 +/- 3.13 years) was performed
      from May to December 2011. Joint hypermobility was assessed using the Beighton
      criteria in all patients. Hernia sacs were analyzed with respect to the total
      antioxidative/oxidative status and prolidase activity. The patients were divided
      into two groups (inguinal hernia with and without hypermobility) according to a
      Beighton score cut-off of >=6. RESULTS: A total of 81 subjects aged 3-10 years
      participated. The ratio of joint hypermobility was significantly higher in
      patients than in controls (p = 0.01). The prolidase activity, total oxidant
      status, and oxidative stress index were higher in tissue samples from patients
      with joint hypermobility (p < 0.001). CONCLUSIONS: Our results show that joint
      hypermobility syndrome is associated with inguinal hernia in children and that
      increased prolidase activity and oxidative stress in tissue samples from patients
      with joint hypermobility syndrome are related to collagen tissue damage and
      turnover.

PMID- 24567178
TI  - The inhibitory effect of a new scFv/tP protein as siRNA delivery system to target
      hWAPL in cervical carcinoma.
AB  - Targeted immunotherapy has become a popular research topic in cancer. The
      development and metastasis of cervical carcinoma are closely related to epidermal
      growth factor (EGF) and EGF-1 receptor (EGFR). We successfully constructed a
      single-chain human anti-EGFR antibody (scFv) and truncated protamine (tP) fusion
      protein (scFV/tP) expression vector using overlap extension PCR. Enzyme-linked
      immunosorbent assay and gel shift assay showed that the fusion protein retained
      the DNA and antigen-binding activity of the original antibody. Using the non
      viral scFv/tP vector as a delivery tool, small interfering RNA (siRNA) of the
      human wings apart-like gene (hWAPL) was effectively transfected into cervical
      cancer HeLa cells. The hWAPL mRNA expression levels were reduced by 97.23% in
      contrast with control cells, and the proliferation capability declined by 66.71%,
      indicating significant inhibition. The present results provide a novel strategy
      for targeted gene therapy and siRNA therapy of EGFR-positive cervical cancers.

PMID- 24567179
TI  - Poland syndrome involving the left hemithorax with dextrocardia and herniation of
      the spleen.
AB  - Poland syndrome is characterised by unilateral absence of the large pectoral
      muscle, ipsilateral symbrachydactyly and occasionally other malformations of the
      anterior chest wall and breast. The condition is more frequent among men and
      usually occurs on the right hemithorax in the unilateral form. This case is
      unique because we believe it is a rare case of Poland syndrome involving the left
      hemithorax along with dextrocardia and herniation of the spleen from the left
      subcostal region. 

PMID- 24567181
TI  - Disseminated tuberculosis manifesting as cholestasis in a patient with AIDS: a
      presentation to remember.
AB  - A 48-year-old man of Indian descent and chronic untreated HIV infection presented
      with a 3-week history of persistent fever, jaundice and a subacute 10-pound
      weight loss. His presentation was notable for a painless cholestatic jaundice. An
      extensive evaluation was pursued around cholestasis and liver disease, with a
      resulting unremarkable workup for viral, bacterial and tick borne infectious
      aetiologies. A CT scan of the abdomen fortuitously revealed incidental pleural
      effusions and a subsequent CT scan of the chest demonstrated miliary infiltrates,
      suspicious for disseminated tuberculosis (TB). The diagnosis was confirmed by
      GeneXpert PCR and culture of induced sputa, which were positive for Mycobacterium
      tuberculosis. We have highlighted this unusual presentation of disseminated TB,
      manifesting initially as cholestasis in a patient with AIDS. 

PMID- 24567182
TI  - A clue in a colour? EBUS-TBNA in the analysis of isolated mediastinal
      lymphadenopathy.
AB  - A 52-year-old female patient with a background history of malignant melanoma was
      referred to the interventional pulmonology unit at Galway University Hospital for
      the investigation of possible intrathoracic recurrence. A CT of the thorax (CT
      thorax) demonstrated mediastinal lymphadenopathy at position 4R, right
      paratracheal region. An endobronchial ultrasound (EBUS) revealed multiple
      enlarged lymph nodes at station 4R. The nodes were heterogeneous with solid and
      cystic elements. Endobronchial ultrasound-guided transbronchial needle aspiration
      (EBUS-TBNA) obtained a black material consistent with malignant melanoma.
      Multiple TBNA samples were obtained and the diagnosis was confirmed
      pathologically by the presence of multiple epithelioid pigmented cells on cell
      block analysis. This case report emphasises the value of EBUS in the assessment
      of metastatic disease and, in particular, how the gross appearance of the sample
      can be suggestive of the diagnosis. 

PMID- 24567183
TI  - Internal herniation through a defect in the transverse mesocolon.
AB  - Internal hernias are rare, constituting 5.8% of all intestinal obstruction cases.
      Congenital transverse mesocolon hernias in adults are specifically rare. We
      hereby present a case of an adult female presenting with acute intestinal
      obstruction. Her CT scan showed classic signs of internal herniations: 'Whirlpool
      sign', crowding of bowel loops in the upper compartment and the absence of caecum
      from the Right Iliac Fossa. At operation, she was found to have a congenital
      defect in the transverse mesocolon, through which have herniated the terminal
      ileum, caecum and the proximal half of the ascending colon. They have furthermore
      rotated 360 degrees  about the axis of the pedicle forming a volvulus. The bowel
      was viable. The herniated bowel was derotated, and reduced through the defect,
      the defect was closed with polydioxanone sutures, and the caecum and ascending
      colon was fixed to the lateral abdominal wall. 

PMID- 24567184
TI  - Congenital giant male anterior urethral diverticulum with calculi.
AB  - Urethral diverticulum is a sac-like outpouching of urethral mucosa. It may be
      anterior or posterior according to anatomical locations. It is less common in men
      than in women. It can be congenital or acquired. Anterior urethral diverticula
      are usually congenital as compared to majority of posterior diverticula which are
      acquired. The most common aetiologies of male acquired diverticula are stricture,
      abscess, trauma or post-hypospadias repair. We report a case of congenital giant
      anterior urethral diverticulum with a calculus which has been managed
      successfully with surgical excision and repair in two layers. 

PMID- 24567185
TI  - Pneumoperitoneum and pneumatosis cystoides intestinalis (PCI) following
      chemotherapy in an adolescent with Hodgkin's lymphoma.

PMID- 24567186
TI  - Functional analysis of three novel cell lines derived from human papillary
      thyroid carcinomas with three different clinical courses.
AB  - Papillary thyroid carcinoma (PTC) is the most frequent thyroid carcinoma. PTC
      cell lines have been of considerable value in studying aspects of thyroid cancer,
      such as gene expression, cell proliferation, and differentiation. Here we report
      three novel PTC lines established from three patients with different backgrounds.
      Case 1 was a 38-year-old woman with PTC in the right thyroid lobe, with no
      metastasis. The cell line was established from the resection sample and named D
      PTC. The cell line consisted of epithelial cells with few lysosomes and showed a
      pavement structure and follicular formation at confluency. There was a little
      pilling up. The secretion of free thyroxin (fT4) and thyroglobulin (Tg) was
      increased by TSH, or GH and IGF-I treatment. Case 2 was a 22-year-old woman with
      PTC initially in the right thyroid lobe, but 4 years after the right lobe
      resection, PTC metastasis was observed in left lobe. The cell line was
      established from a sample of the second resection and named UD-PTC. This cell
      line consisted of small epithelial cells with evident lysosomes and exhibited
      floating cell clusters. The secretion of fT4 and Tg was slightly increased by
      TSH, or GH and IGF-I treatment. Case 3 was an 85-year-old man with PTC and with
      acromegaly. Metastasis was observed at cervical lymph nodes. The cell line was
      derived from the metastasis region and named A-PTC. This cell line consisted of
      small epithelial cells and many lysosomes. The cells frequently showed pilling
      up. The secretion of fT4 and Tg was significantly increased by GH and IGF-I
      treatment. We have established three PTC cell lines with substantial variation in
      their phenotype. The cell lines may be useful for thyroid cancer research. 

PMID- 24567187
TI  - The Arabidopsis CALLOSE DEFECTIVE MICROSPORE1 gene is required for male fertility
      through regulating callose metabolism during microsporogenesis.
AB  - During angiosperm microsporogenesis, callose serves as a temporary wall to
      separate microsporocytes and newly formed microspores in the tetrad. Abnormal
      callose deposition and dissolution can lead to degeneration of developing
      microspores. However, genes and their regulation in callose metabolism during
      microsporogenesis still remain largely unclear. Here, we demonstrated that the
      Arabidopsis (Arabidopsis thaliana) CALLOSE DEFECTIVE MICROSPORE1 (CDM1) gene,
      encoding a tandem CCCH-type zinc finger protein, plays an important role in
      regulation of callose metabolism in male meiocytes and in integrity of newly
      formed microspores. First, quantitative reverse transcription PCR and in situ
      hybridization analyses showed that the CDM1 gene was highly expressed in
      meiocytes and the tapetum from anther stages 4 to 7. In addition, a transfer DNA
      insertional cdm1 mutant was completely male sterile. Moreover, light microscopy
      of anther sections revealed that microspores in the mutant anther were initiated,
      and then degenerated soon afterward with callose deposition defects, eventually
      leading to male sterility. Furthermore, transmission electron microscopy
      demonstrated that pollen exine formation was severely affected in the cdm1
      mutant. Finally, we found that the cdm1 mutation affected the expression of
      callose synthesis genes (CALLOSE SYNTHASE5 and CALLOSE SYNTHASE12) and potential
      callase-related genes (A6 and MYB80), as well as three other putative beta-1,3
      glucanase genes. Therefore, we propose that the CDM1 gene regulates callose
      metabolism during microsporogenesis, thereby promoting Arabidopsis male
      fertility. 

PMID- 24567188
TI  - Origin of beta-carotene-rich plastoglobuli in Dunaliella bardawil.
AB  - The halotolerant microalgae Dunaliella bardawil accumulates under nitrogen
      deprivation two types of lipid droplets: plastoglobuli rich in beta-carotene
      (betaC-plastoglobuli) and cytoplasmatic lipid droplets (CLDs). We describe the
      isolation, composition, and origin of these lipid droplets. Plastoglobuli contain
      beta-carotene, phytoene, and galactolipids missing in CLDs. The two preparations
      contain different lipid-associated proteins: major lipid droplet protein in CLD
      and the Prorich carotene globule protein in betaC-plastoglobuli. The compositions
      of triglyceride (TAG) molecular species, total fatty acids, and sn-1+3 and sn-2
      positions in the two lipid pools are similar, except for a small increase in
      palmitic acid in plastoglobuli, suggesting a common origin. The formation of CLD
      TAG precedes that of betaC-plastoglobuli, reaching a maximum after 48 h of
      nitrogen deprivation and then decreasing. Palmitic acid incorporation kinetics
      indicated that, at early stages of nitrogen deprivation, CLD TAG is synthesized
      mostly from newly formed fatty acids, whereas in betaC-plastoglobuli, a large
      part of TAG is produced from fatty acids of preformed membrane lipids. Electron
      microscopic analyses revealed that CLDs adhere to chloroplast envelope membranes
      concomitant with appearance of small betaC-plastoglobuli within the chloroplast.
      Based on these results, we propose that CLDs in D. bardawil are produced in the
      endoplasmatic reticulum, whereas betaC-plastoglobuli are made, in part, from
      hydrolysis of chloroplast membrane lipids and in part, by a continual transfer of
      TAG or fatty acids derived from CLD. 

PMID- 24567189
TI  - Arabidopsis VASCULAR-RELATED UNKNOWN PROTEIN1 regulates xylem development and
      growth by a conserved mechanism that modulates hormone signaling.
AB  - Despite a strict conservation of the vascular tissues in vascular plants
      (tracheophytes), our understanding of the genetic basis underlying the
      differentiation of secondary cell wall-containing cells in the xylem of
      tracheophytes is still far from complete. Using coexpression analysis and
      phylogenetic conservation across sequenced tracheophyte genomes, we identified a
      number of Arabidopsis (Arabidopsis thaliana) genes of unknown function whose
      expression is correlated with secondary cell wall deposition. Among these, the
      Arabidopsis VASCULAR-RELATED UNKNOWN PROTEIN1 (VUP1) gene encodes a predicted
      protein of 24 kD with no annotated functional domains but containing domains that
      are highly conserved in tracheophytes. Here, we show that the VUP1 expression
      pattern, determined by promoter-beta-glucuronidase reporter gene expression, is
      associated with vascular tissues, while vup1 loss-of-function mutants exhibit
      collapsed morphology of xylem vessel cells. Constitutive overexpression of VUP1
      caused dramatic and pleiotropic developmental defects, including severe dwarfism,
      dark green leaves, reduced apical dominance, and altered photomorphogenesis,
      resembling brassinosteroid-deficient mutants. Constitutive overexpression of VUP
      homologs from multiple tracheophyte species induced similar defects. Whole-genome
      transcriptome analysis revealed that overexpression of VUP1 represses the
      expression of many brassinosteroid- and auxin-responsive genes. Additionally,
      deletion constructs and site-directed mutagenesis were used to identify critical
      domains and amino acids required for VUP1 function. Altogether, our data suggest
      a conserved role for VUP1 in regulating secondary wall formation during vascular
      development by tissue- or cell-specific modulation of hormone signaling pathways.

PMID- 24567190
TI  - Histone H2B monoubiquitination is involved in regulating the dynamics of
      microtubules during the defense response to Verticillium dahliae toxins in
      Arabidopsis.
AB  - Histone H2B monoubiquitination (H2Bub) is being recognized as a regulatory
      mechanism that controls a range of cellular processes in plants, but the
      molecular mechanisms of H2Bub that are involved in responses to biotic stress are
      largely unknown. In this study, we used wild-type and H2Bub loss-of-function
      mutations of Arabidopsis (Arabidopsis thaliana) to elucidate which of its
      mechanisms are involved in the regulation of the plant's defense response to
      Verticillium dahliae (Vd) toxins. We demonstrate that the depolymerization of the
      cortical microtubules (MTs) was different in the wild type and the mutants in the
      response to Vd toxins. The loss-of-function alleles of HISTONE
      MONOUBIQUITINATION1 and HISTONE MONOUBIQUITINATION2 mutations present a weaker
      depolymerization of the MTs, and protein tyrosine phosphorylation plays a
      critical role in the regulation of the dynamics of MTs. Moreover, H2Bub is a
      positive regulator of the gene expression of protein tyrosine phosphatases. These
      findings provide direct evidence for H2Bub as an important modification with
      regulatory roles in the defense against Vd toxins and demonstrate that H2Bub is
      involved in modulating the dynamics of MTs, likely through the protein tyrosine
      phosphatase-mediated signaling pathway. 

PMID- 24567192
TI  - Nearly lattice matched all wurtzite CdSe/ZnTe type II core-shell nanowires with
      epitaxial interfaces for photovoltaics.
AB  - Achieving a high-quality interface is of great importance in core-shell nanowire
      solar cells, as it significantly inhibits interfacial recombination and thus
      improves the photovoltaic performance. Combining thermal evaporation of CdSe and
      pulsed laser deposition of ZnTe, we successfully synthesized nearly lattice
      matched all wurtzite CdSe/ZnTe core-shell nanowires on silicon substrates.
      Comprehensive morphological and structural characterizations revealed that a
      wurtzite ZnTe shell layer epitaxially grows over a wurtzite CdSe core nanowire
      with an abrupt interface. Further optical studies confirmed a high-quality
      interface and demonstrated efficient charge separation induced by the type-II
      band alignment. A representative photovoltaic device has been demonstrated and
      yielded an energy-conversion efficiency of 1.7% which can be further improved by
      surface passivation. The all-wurtzite core-shell nanowire with an epitaxial
      interface offers an attractive platform to explore the piezo-phototronic effect
      and promises an efficient hybrid nano-sized, energy harvesting system. 

PMID- 24567191
TI  - The Solanum lycopersicum Zinc Finger2 cysteine-2/histidine-2 repressor-like
      transcription factor regulates development and tolerance to salinity in tomato
      and Arabidopsis.
AB  - The zinc finger superfamily includes transcription factors that regulate multiple
      aspects of plant development and were recently shown to regulate abiotic stress
      tolerance. Cultivated tomato (Solanum lycopersicum Zinc Finger2 [SIZF2]) is a
      cysteine-2/histidine-2-type zinc finger transcription factor bearing an ERF
      associated amphiphilic repression domain and binding to the ACGTCAGTG sequence
      containing two AGT core motifs. SlZF2 is ubiquitously expressed during plant
      development, and is rapidly induced by sodium chloride, drought, and potassium
      chloride treatments. Its ectopic expression in Arabidopsis (Arabidopsis thaliana)
      and tomato impaired development and influenced leaf and flower shape, while
      causing a general stress visible by anthocyanin and malonyldialdehyde
      accumulation. SlZF2 enhanced salt sensitivity in Arabidopsis, whereas SlZF2
      delayed senescence and improved tomato salt tolerance, particularly by
      maintaining photosynthesis and increasing polyamine biosynthesis, in salt-treated
      hydroponic cultures (125 mm sodium chloride, 20 d). SlZF2 may be involved in
      abscisic acid (ABA) biosynthesis/signaling, because SlZF2 is rapidly induced by
      ABA treatment and 35S::SlZF2 tomatoes accumulate more ABA than wild-type plants.
      Transcriptome analysis of 35S::SlZF2 revealed that SlZF2 both increased and
      reduced expression of a comparable number of genes involved in various
      physiological processes such as photosynthesis, polyamine biosynthesis, and
      hormone (notably ABA) biosynthesis/signaling. Involvement of these different
      metabolic pathways in salt stress tolerance is discussed. 

PMID- 24567193
TI  - Factors associated with persistent poorly controlled diabetes mellitus: clues to
      improving management in patients with resistant poor control.
AB  - OBJECTIVES: Patients with persistent poorly controlled diabetes mellitus (PPDM),
      defined as an uninterrupted hemoglobin A1c >8.0% for >=1 year despite standard
      care, are at high risk for complications. Additional research to define patient
      factors associated with PPDM could suggest barriers to improvement in this group
      and inform the development of targeted strategies to address these patients'
      resistant diabetes. METHODS: We analyzed patients with type 2 diabetes from a
      multi-site randomized trial. We characterized patients with PPDM relative to
      other patients using detailed survey data and multivariable modeling. RESULTS: Of
      963 patients, 118 (12%) had PPDM, 265 (28%) were intermittently poorly
      controlled, and 580 (60%) were well-controlled. Patients with PPDM had younger
      age, earlier diabetes diagnosis, insulin use, higher antihypertensive burden,
      higher low-density lipoprotein cholesterol, and lower statin use relative to well
      controlled patients. Among patients with objective adherence data (Veterans
      Affairs patients), a larger oral diabetes medication refill gap was associated
      with PPDM. DISCUSSION: Strategies are needed to target-specific barriers to
      improvement among patients whose diabetes is resistant to standard diabetes care.
      Our data suggest that strategies for targeting PPDM should accommodate younger
      patients' lifestyles, include medication management for insulin titration and
      comorbid disease conditions, and address barriers to self-management adherence.

PMID- 24567194
TI  - Women's accounts of help-seeking in early rheumatoid arthritis from symptom onset
      to diagnosis.
AB  - BACKGROUND: As interest in gender and health grows, the notion that women are
      more likely than men to consult doctors is increasingly undermined as more
      complex understandings of help seeking and gender emerge. While men's reluctance
      to seek help is associated with practices of masculinities, there has been less
      consideration of women's help-seeking practices. Rheumatoid arthritis (RA) is a
      chronic disease that predominantly affects women and requires prompt treatment
      but considerable patient-based delays persist along the care pathway. This paper
      examines women's accounts of help seeking in early RA from symptom onset to
      diagnosis. METHODS: We conducted in-depth interviews with 37 women with RA <12
      months in Canada. Analysis was based on a constant comparison, thematic approach
      informed by narrative analysis. RESULTS: The women's accounts featured masculine
      practices associated with men's help-seeking. The women presented such behaviours
      as relational, e.g. rooted in family socialisation and a determination to
      maintain roles and 'normal' life. DISCUSSION: Our findings raise questions about
      how far notions of gender operate to differentiate men and women's help seeking
      and may indicate more similarities than differences. Recognising this has
      implications for policy and practice initiatives for both men and women.

PMID- 24567195
TI  - Barriers and facilitators to self-care communication during medical appointments
      in the United States for adults with type 2 diabetes.
AB  - OBJECTIVE: Diabetes self-care is challenging and requires effective patient
      provider communication to achieve optimal treatment outcomes. This study explored
      perceptions of barriers and facilitators to diabetes self-care communication
      during medical appointments. DESIGN: Qualitative study using in-depth interviews
      with a semistructured interview guide. PARTICIPANTS: Thirty-four patients with
      type 2 diabetes and 19 physicians who treat type 2 diabetes. RESULTS: Physicians
      described some patients as reluctant to discuss their self-care behaviors
      primarily because of fear of being judged, guilt, and shame. Similarly, patients
      described reluctant communication resulting from fear of being judged and shame,
      particularly shame surrounding food intake and weight. Physicians and patients
      recommended trust, nonjudgmental acceptance, open/honest communication, and
      providing patients hope for living with diabetes as important factors for
      improving self-care communication. Further, patients stressed the clinical
      benefits of physicians directly addressing poor self-care behaviors while
      physicians described having few strategies to address these difficulties.
      CONCLUSIONS: Physician-patient self-care communication barriers included
      patients' reluctance to discuss self-care behaviors and physicians' perceptions
      of few options to address this reluctance. Treatment recommendations stressed the
      importance of establishing trusting, nonjudgmental and open patient-provider
      communication for optimal diabetes treatment. Medical education is needed to
      improve physicians' strategies for addressing self-care communication during
      medical appointments.

PMID- 24567196
TI  - Primary breast tumor-derived cellular models: characterization of tumorigenic,
      metastatic, and cancer-associated fibroblasts in dissociated tumor (DT) cultures.
AB  - Our goal was to establish primary cultures from dissociation of breast tumors in
      order to provide cellular models that may better recapitulate breast cancer
      pathogenesis and the metastatic process. Here, we report the characterization of
      six cellular models derived from the dissociation of primary breast tumor
      specimens, referred to as "dissociated tumor (DT) cells." In vitro, DT cells were
      characterized by proliferation assays, colony formation assays, protein, and gene
      expression profiling, including PAM50 predictor analysis. In vivo, tumorigenic
      and metastatic potential of DT cultures was assessed in NOD/SCID and NSG mice.
      These cellular models differ from recently developed patient-derived xenograft
      models in that they can be used for both in vitro and in vivo studies. PAM50
      predictor analysis showed DT cultures similar to their paired primary tumor and
      as belonging to the basal and Her2-enriched subtypes. In vivo, three DT cultures
      are tumorigenic in NOD/SCID and NSG mice, and one of these is metastatic to lymph
      nodes and lung after orthotopic inoculation into the mammary fat pad, without
      excision of the primary tumor. Three DT cultures comprised of cancer-associated
      fibroblasts (CAFs) were isolated from luminal A, Her2-enriched, and basal primary
      tumors. Among the DT cells are those that are tumorigenic and metastatic in
      immunosuppressed mice, offering novel cellular models of ER-negative breast
      cancer subtypes. A group of CAFs provide tumor subtype-specific components of the
      tumor microenvironment (TME). Altogether, these DT cultures provide closer-to
      primary cellular models for the study of breast cancer pathogenesis, metastasis,
      and TME. 

PMID- 24567197
TI  - Should we screen BRCA1 mutation carriers only with MRI? A multicenter study.
AB  - BRCA1 mutation carriers are offered screening with MRI and mammography. Aim of
      the study was to investigate the additional value of digital mammography over MRI
      screening. BRCA1 mutation carriers, who developed breast cancer since the
      introduction of digital mammography between January 2003 and March 2013, were
      included. The images and reports were reviewed in order to assess whether the
      breast cancers were screen-detected or interval cancers and whether they were
      visible on mammography and MRI, using the breast imaging and data system
      classification allocated at the time of diagnosis. In 93 BRCA1 mutation carriers
      who underwent screening with MRI and mammography, 82 invasive breast cancers and
      12 ductal carcinomas in situ (DCIS) were found. Screening sensitivity was 95.7 %
      (90/94). MRI detected 88 of 94 breast cancers (sensitivity 93.6 %), and
      mammography detected 48 breast cancers (sensitivity 51.1 %) (two-sided p <
      0.001). Forty-two malignancies were detected only by MRI (42/94 = 44.7 %). Two
      DCIS were detected only with mammography (2/94 = 2.1 %) concerning a grade 3 in a
      50-year-old patient and a grade 2 in a 67-year-old patient. Four interval cancers
      occurred (4/94 = 4.3 %), all grade 3 triple negative invasive ductal carcinomas.
      In conclusion, digital mammography added only 2 % to the breast cancer detection
      in BRCA1 patients. There was no benefit of additional mammography in women below
      age 40. Given the potential risk of radiation-induced breast cancer in young
      mutation carriers, we propose to screen BRCA1 mutation carriers yearly with MRI
      from age 25 onwards and to start with mammographic screening not earlier than age
      40.

PMID- 24567198
TI  - Surgical management of breast cancer in BRCA-mutation carriers: a systematic
      review and meta-analysis.
AB  - This meta-analysis investigates the oncological safety of breast-conserving
      therapy BCT in BRCA-mutation carriers and the risk for contralateral breast
      cancer (CBC) compared with non-carriers, potential risk factors for ipsilateral
      breast recurrence (IBR) or CBC and grades these factors based on the level of
      evidence. A PubMed search was conducted through April 2013 to identify studies
      that described the risk for IBR and CBC after BCT in BRCA-mutation carriers
      versus non-carriers as well as studies that investigated risk factors for IBR and
      CBC in BRCA-mutation carriers. Results were summarized using meta-analysis when
      sufficient studies were available. Ten studies investigated the oncological
      safety of BCT in BRCA-mutation carriers versus non-carriers. There was no
      significant difference in IBR between carriers and controls (RR 1.45, 95 % CI
      0.98-2.14). However, a significant higher risk for IBR in BRCA-mutation carriers
      was observed in studies with a median follow-up >=7 years (RR 1.51, 95 % CI 1.15
      1.98). CBCs were significantly greater in carriers versus controls (RR 3.56, 95 %
      CI 2.50-5.08). Use of adjuvant chemotherapy and oophorectomy were associated with
      a significantly lower risk for IBR in BRCA-mutation carriers. Three factors were
      associated with a lower risk for CBC in BRCA-mutation carriers: oophorectomy, use
      of tamoxifen, and age at first breast cancer. Based on current evidence, the use
      of BCT in BRCA-mutation carriers can be considered a reasonable option since it
      does not seem to increase the risk for IBR. However, several aspects should be
      taken into account before the final decision-making.

PMID- 24567199
TI  - Health care contacts in the year before suicide death.
AB  - BACKGROUND: Suicide prevention is a public health priority, but no data on the
      health care individuals receive prior to death are available from large
      representative United States population samples. OBJECTIVE: To investigate
      variation in the types and timing of health services received in the year prior
      to suicide, and determine whether a mental health condition was diagnosed.
      DESIGN: Longitudinal study from 2000 to 2010 within eight Mental Health Research
      Network health care systems serving eight states. PARTICIPANTS: In all, 5,894
      individuals who died by suicide, and were health plan members in the year before
      death. MAIN MEASURES: Health system contacts in the year before death. Medical
      record, insurance claim, and mortality records were linked via the Virtual Data
      Warehouse, a federated data system at each site. KEY RESULTS: Nearly all
      individuals received health care in the year prior to death (83 %), but half did
      not have a mental health diagnosis. Only 24 % had a mental health diagnosis in
      the 4-week period prior to death. Medical specialty and primary care visits
      without a mental health diagnosis were the most common visit types. The
      individuals more likely to make a visit in the year prior to death (p < 0.05)
      tended to be women, individuals of older age (65+ years), those where the
      neighborhood income was over $40,000 and 25 % were college graduates, and those
      who died by non-violent means. CONCLUSIONS: This study indicates that
      opportunities for suicide prevention exist in primary care and medical settings,
      where most individuals receive services prior to death. Efforts may target
      improved identification of mental illness and suicidal ideation, as a large
      proportion may remain undiagnosed at death.

PMID- 24567200
TI  - Predictors of primary care management of depression in the Veterans Affairs
      healthcare system.
AB  - BACKGROUND: Primary care providers (PCPs) vary in skills to effectively treat
      depression. Key features of evidence-based collaborative care models (CCMs)
      include the availability of depression care managers (DCMs) and mental health
      specialists (MHSs) in primary care. Little is known, however, about the
      relationships between PCP characteristics, CCM features, and PCP depression care.
      OBJECTIVE: To assess relationships between various CCM features, PCP
      characteristics, and PCP depression management. DESIGN: Cross-sectional analysis
      of a provider survey. PARTICIPANTS: 180 PCPs in eight VA sites nationwide. MAIN
      MEASURES: Independent variables included scales measuring comfort and difficulty
      with depression care; collaboration with a MHS; self-reported depression
      caseload; availability of a collocated MHS, and co-management with a DCM or MHS.
      Covariates included provider type and gender. For outcomes, we assessed PCP self
      reported performance of key depression management behaviors in primary care in
      the past 6 months. KEY RESULTS: Response rate was 52 % overall, with 47 %
      attending physicians, 34 % residents, and 19 % nurse practitioners and physician
      assistants. Half (52 %) reported greater than eight veterans with depression in
      their panels and a MHS collocated in primary care (50 %). Seven of the eight
      clinics had a DCM. In multivariable analysis, significant predictors for PCP
      depression management included comfort, difficulty, co-management with MHSs and
      numbers of veterans with depression in their panels. CONCLUSIONS: PCPs who felt
      greater ease and comfort in managing depression, co-managed with MHSs, and
      reported higher depression caseloads, were more likely to report performing
      depression management behaviors. Neither a collocated MHS, collaborating with a
      MHS, nor co-managing with a DCM independently predicted PCP depression
      management. Because the success of collaborative care for depression depends on
      the ability and willingness of PCPs to engage in managing depression themselves,
      along with other providers, more research is necessary to understand how to
      engage PCPs in depression management.

PMID- 24567202
TI  - Translating the hemoglobin A1C with more easily understood feedback: a randomized
      controlled trial.
AB  - INTRODUCTION: Previous work has indicated that for patients with diabetes, there
      is value in understanding glycemic control. Despite these findings, patient
      understanding of the hemoglobin A1C value (A1C) is notably poor. In this study,
      we test the effect of two alternative communication formats of the A1C on
      improving glycemic control among patients with poorly controlled diabetes.
      METHODS: 177 patients with poorly controlled diabetes were randomized to one of
      three study arms that varied in the information they received: (1) a "diabetes
      report card" containing individualized information about glycemic control for
      each participant with letter grades ranging from A to F; (2) a "report card"
      containing a face whose emotion reflected current glycemic control; or (3) a
      "report card" with glycemic control expressed with the A1C value (standard arm).
      The primary study outcome was change in A1C at 6 months. Secondary outcomes
      included changes in participant perceptions of their glycemic control. RESULTS:
      The average A1C for enrolled participants was 9.9 % (S.D. 1.7) and did not differ
      significantly among study arms. We noted no significant differences in change in
      A1C at 6 months between the standard and experimental arms. Using multiple
      imputation to account for missing A1C values, the changes in A1C for the letter
      grade, face, and standard arms were -0.55 % (-1.15, 0.05), -0.89 % (-1.49, 
      0.29), and -0.74 % (-1.51, 0.029), respectively (p = 0.67 for control vs. grade,
      p = 0.76 for control vs. face). DISCUSSION: Feedback to patients with poorly
      controlled diabetes in the form of letter grades and faces did not differentially
      impact glycemic control at 6 months or participant perceptions of current
      control. These efforts to improve communication and patient understanding of
      disease management targets need further refinement to significantly impact
      diabetes outcomes. CLINICAL TRIAL ID: NCT01143870.

PMID- 24567201
TI  - Trends and quality of care in outpatient visits to generalist and specialist
      physicians delivering primary care in the United States, 1997-2010.
AB  - BACKGROUND: Although many specialists serve as primary care physicians (PCPs),
      the type of patients they serve, the range of services they provide, and the
      quality of care they deliver is uncertain. OBJECTIVE: To describe trends in
      patient, physician, and visit characteristics, and compare visit-based quality
      for visits to generalists and specialists self-identified as PCPs. DESIGN: Cross
      sectional study and time trend analysis. DATA: Nationally representative sample
      of visits to office-based physicians from the National Ambulatory Medical Care
      Survey, 1997-2010. MAIN MEASURES: Proportions of primary care visits to
      generalist and specialists, patient characteristics, principal diagnoses, and
      quality. KEY RESULTS: Among 84,041 visits to self-identified PCPs representing an
      estimated 4.0 billion visits, 91.5 % were to generalists, 5.9 % were to medical
      specialists and 2.6 % were to obstetrician/gynecologists. The proportion of PCP
      visits to generalists increased from 88.4 % in 1997 to 92.4 % in 2010, but
      decreased for medical specialists from 8.0 % to 4.8 %, p = 0.04). The proportion
      of medical specialist visits in which the physician self-identified as the
      patient's PCP decreased from 30.6 % in 1997 to 9.8 % in 2010 (p < 0.01). Medical
      specialist PCPs take care of older patients (mean age 61 years), and dedicate
      most of their visits to chronic disease management (51.0 %), while generalist
      PCPs see younger patients (mean age 55.4 years) most commonly for new problems
      (40.5 %). Obstetrician/gynecologists self-identified as PCPs see younger patients
      (mean age 38.3 p < 0.01), primarily for preventive care (54.0 %, p < 0.01).
      Quality of care for cardiovascular disease was better in visits to cardiologists
      than in visits to generalists, but was similar or better in visits to generalists
      compared to visits to other medical specialists. CONCLUSIONS: Medical specialists
      are less frequently serving as PCPs for their patients over time. Generalist,
      medical specialist, and obstetrician/gynecologist PCPs serve different primary
      care roles for different populations. Delivery redesign efforts must account for
      the evolving role of generalist and specialist PCPs in the delivery of primary
      care.

PMID- 24567205
TI  - Obtaining gametes and embryos of ascidians.
AB  - Ascidians are basal chordates that have become increasingly important for
      understanding chordate evolution. They comprise three orders. In the orders
      Phlebobranchia and Stolidobranchia, most species freely spawn eggs and sperm,
      whereas members of the order Aplousobranchia form colonies that brood their eggs
      and broadcast sperm. In the two free spawning orders, eggs and sperm are easily
      obtained for in vitro fertilizations. In the third order, slices of colonies
      yield gametes and embryos of all stages. Methods are described for obtaining
      gametes, performing fertilizations, and culturing embryos. Also included are
      methods for removing follicle cells and vitelline coats from oocytes.

PMID- 24567204
TI  - Culturing larvae of marine invertebrates.
AB  - Larvae of marine invertebrates cultured in the laboratory experience conditions
      that they do not encounter in nature, but development and survival to metamorphic
      competence can be obtained in such cultures. This protocol emphasizes simple
      methods suitable for a wide variety of larvae. Culturing larvae requires seawater
      of adequate quality and temperature within the tolerated range. Beyond that,
      feeding larvae require appropriate food, but a few kinds of algae and animals are
      sufficient as food for diverse larvae. Nontoxic materials include glass, many
      plastics, hot-melt glue, and some solvents, once evaporated. Cleaners that do not
      leave toxic residues after rinsing include dilute hydrochloric or acetic acid,
      sodium hypochlorite (commercial bleach), and ethanol. Materials that can leave
      toxic residues, such as formaldehyde, glutaraldehyde, detergents, and hand
      lotions, should be avoided, especially with batch cultures that lack continuously
      renewed water. Reverse filtration can be used to change water gently at varying
      frequencies, depending on temperature and the kinds of food that are provided.
      Bacterial growth can be limited by antibiotics, but antibiotics are often
      unnecessary. Survival and growth are increased by low concentrations of larvae
      and stirring of large or dense cultures. One method of stirring large numbers of
      containers is a rack of motor-driven paddles. Most of the methods and materials
      are inexpensive and portable. If necessary, a room within a few hours of the sea
      could be temporarily equipped for larval culture. 

PMID- 24567203
TI  - Analysis of randomized controlled trials in Rheumatology International from 1981
      to 2012: methodological assessment.
AB  - The aim of the study is to assess the methodological quality of randomized
      controlled trials (RCTs) published in Rheumatology International (RI) by using
      three types of analytical tools. MEDLINE was used to extract RCTs from original
      articles published in the RI from 1981 (vol. 1) to 2012 (vol. 32). The
      relationship between the number of articles and RCTs with time and that between
      various factors and the quality of RCTs were analyzed. To analyze the
      methodological quality of the RCTs, the time period was divided into several
      sections and three tools were applied (e.g., the Jadad scale, van Tulder scale,
      and Cochrane Collaboration Risk of Bias Tool). The number of RCTs published
      gradually increased with time significantly (p < 0.001). The differences in RCT
      quality scores by each method in the publication years evaluated were not
      statistically significant, but RCTs that included descriptions of allocation
      concealment methods had received institutional review board (IRB) approval, and
      that conducted in the multicenter had significantly higher-quality scores than
      other studies. In conclusion, although the number of RCTs published in RI since
      its publishing in 1981 has increased with time, but no qualitative improvement of
      RCT was observed over time. It is necessary to improve the reporting of
      concealment of allocation, generation of randomization sequences, design of
      blinded studies, and obtaining IRB approval, all of which are criteria of high
      quality RCTs.

PMID- 24567206
TI  - Artificial seawater culture of the gastropod Crepidula fornicata for studies of
      larval settlement and metamorphosis.
AB  - The slipper limpet, Crepidula fornicata, is a gastropod mollusc of growing
      importance as a research model in developmental biology and as an invasive
      organism. The large (>1 mm) veliger larvae of this species are well suited for
      neuroethological investigations of settlement and metamorphosis. In this chapter,
      methods are described for conditioning adult broodstock, growing microalgal food
      for larvae, and culturing larvae to metamorphic competence in artificial
      seawater. A protocol is also presented for obtaining electrophysiological
      recordings of ciliary arrest spikes from intact, behaving larvae, as putative
      neural correlates of larval settlement.

PMID- 24567207
TI  - Trichoplax adhaerens, an enigmatic basal metazoan with potential.
AB  - Trichoplax adhaerens is an enigmatic basal animal with an extraordinarily simple
      morphological organization and surprisingly complex behaviors. Basic
      morphological, molecular and behavioral work is essential to better understand
      the unique and curious life style of these organisms. We provide basic
      instructions on how Trichoplax can be cultured and studied in the laboratory
      emphasizing behavioral and cellular aspects. 

PMID- 24567208
TI  - Rearing gymnolaemate bryozoan larvae for cellular and molecular analyses.
AB  - Gymnolaemates represent the largest group of extant bryozoans, having more than
      3,000 described species. Gymnolaemates display a diverse array of reproductive
      and developmental patterns including planktotrophy, lecithotrophy, and
      matrotrophy. The larvae of gymnolaemates have been broadly grouped into three
      types, cyphonautes (shelled, feeding), pseudocyphonautes (shelled, nonfeeding),
      and coronate (unshelled, nonfeeding), although each group is heterogeneous and
      probably includes various morphologies that are largely undescribed. Here,
      methods for rearing bryozoan colonies and larvae are presented.

PMID- 24567209
TI  - An invertebrate embryologist's guide to routine processing of confocal images.
AB  - It is almost impossible to use a confocal microscope without encountering the
      need to transform the raw data through image processing. Adherence to a set of
      straightforward guidelines will help ensure that image manipulations are both
      credible and repeatable. Meanwhile, attention to optimal data collection
      parameters will greatly simplify image processing, not only for convenience but
      for quality and credibility as well. Here I describe how to conduct routine
      confocal image processing tasks, including creating 3D animations or stereo
      images, false coloring or merging channels, background suppression, and
      compressing movie files for display.

PMID- 24567210
TI  - TEM analyses of chaetognath reproductive organs.
AB  - Transmission electron microscopy (TEM) enables analysis of subcellular
      organization. It is especially useful for describing the diverse array of cell
      types in the gonads and embryos of marine invertebrates. Here, I describe methods
      for preserving and embedding the reproductive organs of marine arrow worms for
      TEM, including procedures for staining thick sections for light microscopy and
      thin sections for TEM. 

PMID- 24567211
TI  - SEM analysis of marine invertebrate gametes.
AB  - Scanning electron microscopy (SEM) enables a close-up investigation of
      topographical features at the cellular level down to a resolution of about 3 nm.
      In terms of gametes this allows for examination of minute surface details and
      changes that occur during fertilization. Sometimes these features are hidden from
      view and must be carefully exposed during preparation in order to be made visible
      in the SEM. This chapter describes methods that can reveal surface details of
      gametes for observation, as well as fix them permanently, while keeping fixation
      artifacts to a minimum. 

PMID- 24567212
TI  - Imaging neural development in embryonic and larval sea urchins.
AB  - Imaging is a critical tool in neuroscience, and our understanding of the
      structure and function of sea urchin nervous systems owes much to this approach.
      In particular, studies of neural development have been facilitated by methods
      that enable the accurate identification of specific types of neurons. Here we
      describe methods that have been successfully employed to study neural development
      in sea urchin embryos. Altering gene expression in part of an embryo is
      facilitated by injection of reagents into individual blastomeres, which enables
      studies of cell autonomous effects and single embryo rescue experiments. The
      simultaneous localization of an in situ RNA hybridization probe and a cell type
      specific antigen has enabled studies of gene expression in specific types of
      neurons. Fixatives and antibodies can be capricious; thus, we provide data on
      preservation of antigens with commonly used fixatives and buffers.

PMID- 24567213
TI  - Preparation and use of sea urchin egg homogenates.
AB  - Cell homogenates provide a simple and yet powerful means of investigating the
      actions of Ca(2+)-mobilizing second messengers and their target Ca(2+) stores.
      The sea urchin egg homogenate is particularly useful and almost unique in
      retaining robust Ca(2+) responses to all three major messengers, i.e., inositol
      1,4,5-trisphosphate (IP3), cyclic ADP-ribose, and nicotinic acid adenine
      dinucleotide phosphate (NAADP) (Lee and Aarhus. J Biol Chem 270: 2152-2172,
      1995). It is not only invaluable for probing the pharmacology and mechanism of
      action of these messengers, but can also be used to assay Ca(2+) uptake
      mechanisms (Churchill et al. Cell 111: 703-708, 2002), second messenger
      production (Morgan et al. Methods in cADPR and NAADP research. In: Putney JW Jr
      (ed) Methods in calcium signalling, CRC: Boca Raton, FL, 2006), and dynamics of
      luminal pH (pHL) changes within acidic Ca(2+) stores (Lee and Epel. Dev Biol 98:
      446-454, 1983; Morgan and Galione. Biochem J 402: 301-310, 2007). Here, we detail
      the protocols for preparing and using egg homogenates, wherein eggs are shed and
      collected into artificial sea water (ASW), dejellied, washed several times in
      Ca(2+)-free ASW, and then finally washed and resuspended in an intracellular-like
      medium. Homogenization is effected with a Dounce glass tissue homogenizer (at 50
      % (v/v)) and aliquots frozen and stored at -80  degrees C. For Ca(2+) (or pHL)
      measurements, homogenate is thawed and sequentially diluted in an intracellular
      like medium and the fluorescence of Ca(2+)- or pHL-sensitive dyes monitored in a
      standard fluorimeter or plate-reader.

PMID- 24567214
TI  - Microinjection and 4D fluorescence imaging in the eggs and embryos of the
      ascidian Phallusia mammillata.
AB  - Time-lapse 4D imaging of fluorescently tagged proteins to follow the dynamics of
      cellular structures (chromosomes, microtubules, actin, centrosomes, cortical
      structures like the CAB in ascidians, etc.) combined with targeted gene knockdown
      during embryonic development is a powerful technique to understand the mechanisms
      of embryonic development. The eggs and embryos of the primitive marine chordate
      Phallusia mammillata are an excellent model system for combining live cell
      imaging with gene knockdown experiments. Here we describe simple methods for
      microinjecting Phallusia eggs with mRNA encoding fluorescent fusion proteins
      combined with 4D time-lapse imaging techniques we use to follow all of embryonic
      development from the egg to late tailbud stage.

PMID- 24567215
TI  - Isolating specific embryonic cells of the sea urchin by FACS.
AB  - Isolating cells based on specific gene expression enables a focused biochemical
      and molecular analysis. While cultured cells and hematopoietic cells, for
      example, are routinely isolated by fluorescence activated cell sorting (FACS),
      early embryonic cells are a relatively untapped source for FACS applications
      often because the embryos of many animals are quite limiting. Furthermore, many
      applications require genetic model organisms in which cells can be labeled by
      fluorescent transgenes, or antibodies against cell surface antigens. Here we
      define conditions in the sea urchin embryo for isolation of embryonic cells based
      on expression of specific proteins. We use the sea urchin embryo for which a
      nearly unlimited supply of embryonic cells is available and demonstrate the
      conditions for separation of the embryo into single cells, fixation of the cells
      for antibody penetration into the cells, and conditions for FACS of a rare cell
      type in the embryo. This protocol may be adapted for analysis of mRNA, chromatin,
      protein, or carbohydrates and depends only on the probe availability for the cell
      of interest. We anticipate that this protocol will be broadly applicable to
      embryos of other species. 

PMID- 24567216
TI  - Biotinylation of oocyte cell surface proteins of the starfish Patiria miniata.
AB  - Understanding the signal transduction processes that occur during oocyte
      maturation and fertilization requires knowledge of the constituent proteins from
      the cell surface to relevant intracellular compartments. To identify starfish
      oocyte and egg cell surface proteins, a biotinylation method was adapted from
      prior protocols using B cells, leukocytes, mouse oocytes, and sea urchin eggs
      (Cole et al. Mol Immunol 24:699-705, 1987; Flaherty and Swann NJ. Mol Reprod Dev
      35:285-292, 1993; Haley and Wessel. Dev Biol 272:191-202, 2004; Hurley et al. J
      Immunol Methods 85:195-202, 1985). This method utilizes the water-soluble Sulfo
      NHS-Biotin, which does not cross the egg plasma membrane. The process of
      biotinylation does not appear to have any effect on the process of oocyte
      maturation or fertilization. Furthermore, it can be used with either vitelline
      intact or vitelline-free oocytes and allows the proteins to be visualized
      successfully through immunoblotting, immunoprecipitation, or by scanning confocal
      microscopy.

PMID- 24567217
TI  - Perturbations to the hedgehog pathway in sea urchin embryos.
AB  - The Hedgehog pathway has been shown to be an important developmental signaling
      pathway in many organisms (Ingham and McMahon. Genes Dev 15:3059-3087, 2001).
      Recently that work has been extended to developing echinoderm embryos (Walton et
      al. Dev Biol 331(1):26-37, 2009). Here we describe several methods to perturb the
      Hedgehog signaling pathway in the sea urchin. These include microinjection of
      Morpholinos and mRNA constructs as well as treatments with small molecule
      inhibitors. Finally we provide simple methods for assaying Hedgehog phenotypes in
      the sea urchin embryo.

PMID- 24567218
TI  - Regulation of DNA synthesis at the first cell cycle in the sea urchin in vivo.
AB  - Using fluorescent and non-fluorescent recombinant proteins has proved to be a
      very successful technique for following postfertilization events, in both male
      and female pronuclei during the first cell cycle of sea urchin in vivo. Proteins
      and dyes are introduced by microinjection into the unfertilized egg, and their
      function can be monitored by fluorescence or confocal/two-photon (2P) and
      transmitted light microscopy after insemination. Here, we describe expression and
      purification of GFP/RFP-tagged proteins involved in regulation of DNA
      replication. We also explain the techniques used to introduce recombinant
      proteins and fluorescent tubulin into sea urchin eggs and embryos. 

PMID- 24567219
TI  - Immunoblotting analyses of changes in protein phosphorylations during oocyte
      maturation in marine nemertean worms.
AB  - Immunoblotting analyses combined with phospho-specific antibodies can provide a
      powerful means for assessing protein activity states in various cellular
      extracts. This chapter describes a traditional, film-based immunoblotting method
      for monitoring the phosphorylation status of proteins in marine nemertean oocytes
      undergoing maturation. Similarly, with minor modifications, the protocol could
      potentially be applied to a wider variety of cellular processes and extract types
      that might be analyzed in other investigations of marine invertebrate
      development.

PMID- 24567221
TI  - A 96-well plate format for detection of marine zooplankton with the sandwich
      hybridization assay.
AB  - The sandwich hybridization assay (SHA) is a ribosomal RNA (rRNA) targeted
      molecular method used to detect specific target organisms from diverse
      communities found in environmental water samples. This sensitive, robust assay is
      particularly useful for detecting zooplankton, including copepod grazers or
      reproductive propagules from broadcast spawning invertebrates. Herein, I describe
      the most basic application of this flexible methodology-a 96-well plate format
      for analysis of water samples in the laboratory. A microarray format SHA is also
      available and uses the same basic chemistry for remote, robotically mediated, in
      situ target detection. Traditionally produced only in the laboratory,
      preassembled SHA reagents and consumables are now also available for purchase.

PMID- 24567220
TI  - Multicolor labeling in developmental gene regulatory network analysis.
AB  - The sea urchin embryo is an important model system for developmental gene
      regulatory network (GRN) analysis. This chapter describes the use of multicolor
      fluorescent in situ hybridization (FISH) as well as a combination of FISH and
      immunohistochemistry in sea urchin embryonic GRN studies. The methods presented
      here can be applied to a variety of experimental settings where accurate spatial
      resolution of multiple gene products is required for constructing a developmental
      GRN. 

PMID- 24567222
TI  - Isolation and assessment of signaling proteins from synchronized cultures during
      egg activation and through the egg-to-embryo transition in sea urchins.
AB  - Sea urchins are an excellent model system for investigating fertilization
      mechanisms and fundamental cell biological phenomenon such as release from
      quiescence, cell division, secretion, and basic signal transduction. The ease of
      gamete collection, fertilization, and culture is complemented by exquisite
      developmental synchronicity and the ability to carry out both large-scale
      biochemical studies and single-cell experiments. In particular, fertilization in
      echinoderms serves as a paradigm for a digital signaling event-a one-time only
      switch that launches the egg into the developmental pathway. Sperm-induced egg
      activation is dependent on the release of calcium from internal stores and
      subsequent effects on a myriad of cellular events such as exocytosis,
      cytoskeletal remodeling, and cell cycle reentry. Here we describe methods to
      investigate individual signaling proteins as well as global proteomic and
      phosphoproteomic changes involved in the initial steps of egg activation through
      the egg-to-embryo transition.

PMID- 24567223
TI  - Tools for sea urchin genomic analysis.
AB  - The Sea Urchin Genome Project Web site, SpBase ( http://SpBase.org ), in
      association with a suite of publicly available sequence comparison tools provides
      a platform from which to analyze genes and genomic sequences of sea urchin. This
      information system is specifically designed to support laboratory bench studies
      in cell and molecular biology. In particular these tools and datasets have
      supported the description of the gene regulatory networks of the purple sea
      urchin S. purpuratus. This chapter details methods to undertake in the first
      steps to find genes and noncoding regulatory sequences for further analysis.

PMID- 24567224
TI  - Antibody inhibition of protein activity in starfish oocytes.
AB  - Antibodies are widely utilized in cell and molecule biology for immunoblots,
      immunostaining, immunoprecipitation, immunoaffinity purification, and
      immunoassay. Some antibodies can be used for in vivo inhibition experiments.
      These antibodies bind to their target molecules and neutralize their functions,
      providing functional information in the study of their biological role. Here, we
      describe our methods for obtaining inhibitory antibodies against desired
      proteins. We then describe in the starfish oocyte system how to inhibit a target
      protein, even in the nucleus, by injection of antibody into the cytoplasm, and
      how to evaluate antibody inhibition of cell cycle regulators in small numbers of
      oocytes. 

PMID- 24567225
TI  - Immunophotoaffinity labeling of the binding proteins for 1-methyladenine, an
      oocyte maturation-inducing hormone of starfish.
AB  - Starfish oocytes are naturally arrested at the prophase stage of the first
      meiotic division and resume meiosis in response to 1-methyladenine (1-MeAde), the
      oocyte maturation-inducing hormone of starfish. Putative receptors for 1-MeAde
      have not yet been characterized biochemically, although the specific binding of 1
      MeAde to the isolated cortices of starfish oocytes was reported so far. Based on
      the structure-activity relationship of 1-MeAde analogs, we have designed a
      photoaffinity labeling reagent. The photoaffinity labeling of oocyte membrane
      fractions, followed by immunoblotting analysis with anti-1-MeAde antibody,
      results in the detection of an almost single protein band. This 1-MeAde-binding
      protein might be a possible candidate of the maturation-inducing hormone receptor
      of starfish.

PMID- 24567227
TI  - Early cognitive and physical rehabilitation: one step towards improving post
      critical illness outcomes.

PMID- 24567228
TI  - An anterior chest wall abscess penetrating the pleural cavity.

PMID- 24567226
TI  - Brain-derived neurotrophic factor: its impact upon neuroplasticity and
      neuroplasticity inducing transcranial brain stimulation protocols.
AB  - Val66Met (rs6265) is a gene variation, a single nucleotide polymorphism (SNP) in
      the brain-derived neurotrophic factor (BDNF) gene that codes for the protein
      BDNF. The substitution of Met for Val occurs at position 66 in the pro-region of
      the BDNF gene and is responsible for altered activity-dependent release and
      recruitment of BDNF in neurons. This is believed to manifest itself in an altered
      ability in neuroplasticity induction and an increased predisposition toward a
      number of neurological disorders. Many studies using neuroplasticity-inducing
      protocols have investigated the impact of the BDNF polymorphism on cortical
      modulation and plasticity; however, the results are partly contradictory and
      dependent on the paradigm used in a given study. The aim of this review is to
      summarize recent knowledge on the relationship of this BDNF SNP and
      neuroplasticity. 

PMID- 24567231
TI  - If a man needs a gynecologist, will he be able to find one?

PMID- 24567230
TI  - Haplotype-based study of the association of alcohol and acetaldehyde-metabolising
      genes with alcohol dependence (with or without comorbid anxiety symptoms) in a
      Cape Mixed Ancestry population.
AB  - Alcohol dependence (AD) has a large heritable component. Genetic variation in
      genes involved in the absorption and elimination of ethanol have been associated
      with AD. However, some of these polymorphisms are not present in an African
      population. Previous studies have reported that a type of AD which is
      characterized by anxious behaviour may be a genetically specific subtype of AD.
      We investigated whether variation in genes encoding cytochrome P450 2E1 (CYP2E1)
      or acetaldehyde-metabolising enzymes (ALDH1A1, ALDH2) might alter the risk of AD,
      with and without symptoms of anxiety, in a Cape population with mixed ancestry.
      Eighty case control pairs (one with AD, one without AD) were recruited and
      individually matched for potential confounders. Genotype data were available for
      29 single-nucleotide polymorphisms (SNPs) across the three genes. Linkage
      disequilibrium D' values were evaluated for all pairwise comparisons. Allele and
      haplotype frequencies were compared between cases and controls using a chi2 test.
      The ACAG haplotype in block 4 of the ALDH1A1 gene provided evidence of an
      association with AD (p = 0.03) and weak evidence of an association with AD
      without symptoms of anxiety (p = 0.06). When a genetic score was constructed
      using SNPs showing nominal evidence of association with AD, every extra risk
      allele increased the odds of AD by 35% (OR 1.35, 95% CI 1.08, 1.68, p = 0.008)
      and the odds of having AD with anxiety symptoms increased by 53% (OR 1.53, 95% CI
      1.14, 2.05, p = 0.004). Although our results are supported by previous studies in
      other populations, they must be interpreted with caution due to the small sample
      size and the potential influence of population stratification.

PMID- 24567232
TI  - A quantitative method to evaluate the donor corneal tissue quality used in a
      comparative study between two hypothermic preservation media.
AB  - To standardize a new evaluation technique for calculating the overall quality
      (OQ) of the donor cornea and validate it using a comparative study of corneas
      preserved in Optisol-GS and Cornea Cold(r). Thirty pairs of donor corneas were
      selected for a 4 week in vitro comparative study using masked observers.
      Physiological parameters like thickness, transparency, viable endothelial cell
      density (VECD) and morphology were transformed to numerical range (0-4) to obtain
      the OQ. Microbiological examination was performed using Bactec instrument.
      Students t test showed statistically better results (p < 0.05) from week 3 for
      thickness, week 2 for transparency and week 1 for morphology and VECD;
      statistical significance (p < 0.05) was found for OQ from week 2 for the corneas
      preserved in Cornea Cold(r) compared to Optisol-GS. Epithelial quality was
      similar regardless of the medium. Microbiological examination showed absence of
      aerobic and anaerobic microorganisms in both media. OQ method is efficient,
      consistent and easy, now validated for comparative studies. Further refinement is
      necessary for its use at eye-banks, bio-banks and research or transplantation
      purposes. Cornea Cold(r) is a promising hypothermic corneal storage medium with
      preservation time <=21 days. This permits higher flexibility, evaluation
      accuracy, longer duration for surgical preparation and ease of transportation.

PMID- 24567229
TI  - Brain edema in acute liver failure: mechanisms and concepts.
AB  - Brain edema and associated increase in intracranial pressure continue to be
      lethal complications of acute liver failure (ALF). Abundant evidence suggests
      that the edema in ALF is largely cytotoxic brought about by swelling of
      astrocytes. Elevated blood and brain ammonia levels have been strongly implicated
      in the development of the brain edema. Additionally, inflammation and sepsis have
      been shown to contribute to the astrocyte swelling/brain edema in the setting of
      ALF. We posit that ammonia initiates a number of signaling events, including
      oxidative/nitrative stress (ONS), the mitochondrial permeability transition
      (mPT), activation of the transcription factor (NF-kappaB) and signaling kinases,
      all of which have been shown to contribute to the mechanism of astrocyte
      swelling. All of these factors also impact ion-transporters, including Na(+),
      K(+), Cl(-) cotransporter and the sulfonylurea receptor 1, as well as the water
      channel protein aquaporin-4 resulting in a perturbation of cellular ion and water
      homeostasis, ultimately resulting in astrocyte swelling/brain edema. All of these
      events are also potentiated by inflammation. This article reviews contemporary
      knowledge regarding mechanisms of astrocyte swelling/brain edema formation which
      hopefully will facilitate the identification of therapeutic targets capable of
      mitigating the brain edema associated with ALF. 

PMID- 24567233
TI  - Safety, tolerability, and feasibility of antifungal prophylaxis with micafungin
      at 2 mg/kg daily in pediatric patients undergoing allogeneic hematopoietic stem
      cell transplantation.
AB  - INTRODUCTION: Micafungin (MCFG) is used for the prophylaxis of invasive fungal
      disease (IFD) after allogeneic hematopoietic stem cell transplantation (HSCT).
      However, the safety, efficacy, or optimal dosage/blood levels as prophylaxis is
      uncertain in pediatric HSCT-patients. METHODS: We prophylactically administered
      MCFG at 2 mg/kg once daily to 38 children and adolescents undergoing allogeneic
      HSCT. RESULTS: During MCFG prophylaxis, infusion reactions or adverse events
      (grades 2-5) related to MCFG use were not found in all the patients. Thus, MCFG
      prophylaxis was not discontinued and other antifungal agents were not added
      except for 2 patients in whom probable or possible IFDs developed (completion
      rate, 94.7 %). To elucidate the influence of HSCT-related complications/drugs on
      blood concentration of MCFG, we determined the plasma trough and peak levels in
      13 and 10 among 38 patients, respectively. The mean trough and peak levels were
      3.04 +/- 1.21 MUg/mL (569 samples) and 9.63 +/- 3.62 MUg/mL (44 samples),
      respectively. The peak levels were moderately correlated to the trough levels (R
      (2) = 0.466). In a patient, the trough level of MCFG transiently increased up to
      10.21 MUg/mL during hepatic dysfunction due to acute graft-versus-host disease.
      The MCFG trough levels strongly correlated with T-Bil value (R (2) = 0.894).
      There was no relationship between the trough levels of MCFG and the circulating
      concentrations of tacrolimus (R (2) = 0.040). Additionally, MCFG levels were not
      influenced by treatment with cyclophosphamide or corticosteroids. CONCLUSIONS:
      Prophylaxis with MCFG at 2 mg/kg once daily may be safe, tolerable, and feasible
      in pediatric HSCT-patients.

PMID- 24567234
TI  - Titania nanobundle networks as dye-sensitized solar cell photoanodes.
AB  - Quasi-one-dimensional (1D) titania nanobundles were synthesized via a
      hydrothermal method and used to print random network nanostructured films. These
      films are shown to be ideally suited for application as photoanodes in dye
      sensitized solar cells (DSCs) as they have a higher porosity compared to the
      traditional 1D nanostructured TiO2 materials. Devices constructed using the N719
      dye and iodide/triiodide as the redox mediator in the electrolyte yielded energy
      conversion efficiencies (eta = 6.1 +/- 0.2%), which were marginally lower than
      for devices made with the commonly used P25 titania films (eta = 6.3 +/- 0.1%)
      under one sun simulated solar radiation. Application of an electrolyte based on
      the [Co(bpy)3](2+/3+) redox couple and the MK2 organic sensitizer resulted in
      higher efficiencies (eta = 7.70 +/- 0.1%) than for the P25 devices (eta = 6.3 +/-
      0.3%). Each performance parameter (short circuit current density, open circuit
      voltage and fill factor) was higher for the TiO2 nanobundle devices than those
      for the P25-based devices. The results of electrochemical impedance spectroscopy
      (EIS), intensity-modulated photovoltage spectroscopy (IMVS), and dye-loading
      measurements indicated that the better performance of TiO2 nanobundle devices
      with cobalt electrolytes correlates with higher porosity, relatively fast
      electron transport and more efficient suppression of electron recombination. A
      faster rate of diffusion of the cobalt complexes through the highly porous TiO2
      nanobundle network is proposed to contribute to the enhanced device efficiency. 

PMID- 24567235
TI  - Impact of sirolimus-eluting stent fractures without early cardiac events on long
      term clinical outcomes: a multislice computed tomography study.
AB  - OBJECTIVES: This study sought to evaluate the impact of sirolimus-eluting stent
      (SES) fractures on long-term clinical outcomes using multislice computed
      tomography (MSCT). METHODS: In this study, 528 patients undergoing 6- to 18-month
      follow-up 64-slice MSCT after SES implantation without early clinical events were
      followed clinically (the median follow-up interval was 4.6 years). A CT-detected
      stent fracture was defined as a complete gap with Hounsfield units (HU) <300 at
      the site of separation. The major adverse cardiac events (MACEs), including
      cardiac death, stent thrombosis, and target lesion revascularisation, were
      compared according to the presence of stent fracture. RESULTS: Stent fractures
      were observed in 39 patients (7.4 %). MACEs were more common in patients with CT
      detected stent fractures than in those without (46 % vs. 7 %, p < 0.01).
      Univariate Cox regression analysis indicated a significant relationship between
      MACE and stent fracture [hazard ratio (HR) 7.65; p < 0.01], age (HR 1.03; p =
      0.04), stent length (HR 1.03; p < 0.01), diabetes mellitus (HR 1.77; p = 0.04),
      and chronic total occlusion (HR 2.54; p = 0.01). In the multivariate model, stent
      fracture (HR 5.36; p < 0.01) and age (HR 1.03; p = 0.04) remained significant
      predictors of MACE. CONCLUSIONS: An SES fracture detected by MSCT without early
      clinical events was associated with long-term clinical adverse events. KEY
      POINTS: * Long-term outcomes of sirolimus-eluting stent fracture have not been
      fully clarified. * MSCT could detect stent fracture with high accuracy. *
      Sirolimus-eluting stent fracture detected by MSCT was associated with long-term
      adverse events.

PMID- 24567236
TI  - Author reply: To PMID 23362021.

PMID- 24567237
TI  - Effectiveness of remote monitoring of cardiac implantable electronic devices in
      detection and treatment of clinical and device-related cardiovascular events in
      daily practice: the HomeGuide Registry.

PMID- 24567238
TI  - The enthesopathy of celiac patients: effects of gluten-free diet.
AB  - Celiac disease (CD) is a gluten-sensitive enthesopathy occurring in genetically
      predisposed individuals that is caused by a permanent intolerance to gluten. The
      major environmental factor associated with the risk of developing celiac-related
      complications is persistent exposure to dietary gluten. The aim of this study was
      to determine the prevalence of lower limb enthesopathy in CD patients at first
      diagnosis compared with CD patients on a gluten-free diet (GFD). Fifty-five
      untreated CD patients (group A) and 55 CD patients on a GFD from at least 1 year
      (group B), matched for age and sex, attending gastroenterology outpatient clinic
      of the University Federico II of Naples, were enrolled in this study. All
      patients underwent clinical and ultrasonography examination. Among group A, 27
      (49.8 %) patients presented at least one entheseal alteration as compared with 15
      patients (27.2 %) of group B (prevalence rate ratio 1.83, I.C. 95 % = 0.48-7.01;
      p < 0.001). The Glasgow ultrasound enthesitis scoring system (GUESS) was
      significantly higher in patients of group A than in patients of group B. In
      conclusion, our study shows that enthesopathy is more frequent in untreated CD
      subjects with positive anti-tissue transglutaminase antibodies title, as compared
      to those on GFD and absence of serum anti-tissue transglutaminase antibodies
      title. 

PMID- 24567239
TI  - X-linked agammaglobulinemia combined with juvenile idiopathic arthritis and
      invasive Klebsiella pneumoniae polyarticular septic arthritis.
AB  - X-linked agammaglobulinemia (XLA) is a primary immunodeficiency disease caused by
      mutations in the Bruton's tyrosine kinase (BTK) gene. XLA can also present in
      combination with juvenile idiopathic arthritis (JIA), the major chronic
      rheumatologic disease in children. We report herein the first known case of a
      juvenile patient diagnosed with XLA combined with JIA that later developed into
      invasive Klebsiella pneumoniae polyarticular septic polyarthritis. An additional
      comprehensive review of XLA combined with JIA and invasive K. pneumoniae septic
      arthritis is also presented. XLA was identified by the detection of BTK mutations
      while the diagnosis of JIA was established by clinical and laboratory
      assessments. Septic arthritis caused by invasive K. pneumoniae was confirmed by
      culturing of the synovia and gene detection of the isolates. Invasive K.
      pneumoniae infections can not only result in liver abscesses but also septic
      arthritis, although this is rare. XLA combined with JIA may contribute to
      invasive K. pneumoniae infection. 

PMID- 24567240
TI  - Mean platelet volume as an indicator of disease activity in juvenile SLE.
AB  - The aim of the study was to assess mean platelet volume (MPV) in children with
      systemic lupus erythematosus (SLE) at the active and inactive stages. Twenty
      children with SLE and 30 age- and gender-matched controls were enrolled.
      Demographic data, SLE disease activity index (SLEDAI), erythrocyte sedimentation
      rate (ESR), C-reactive protein (CRP), MPV, complement 3 (C3), complement 4 (C4),
      urine protein (Up), and urine creatinine (Ucr) values upon reactivation and
      remission phases were recorded. MPV was statistically higher in patients than in
      controls and significantly increased in active phase compared to inactive phase
      (p = 0.001). A MPV level of 8.4 fL was determined as predictive cutoff value of
      activation of SLE (sensitivity 75 %, specificity 90 %). MPV was positively
      correlated with SLEDAI (p = 0.01, r = 0.55), ESR (p = 0.01, r = 0.45), CRP (p =
      0.04, r = 0.24), and Up/Ucr (p = 0.01, r = 0.45) and negatively correlated with
      C3 (p = 0.02, r = -0.36), albumin (p = 0.01, r = -0.63), and Hb (p = 0.01, r = 
      0.48). There was not any significant association between MPV and the histological
      classification of lupus nephritis (p = 0.65). MPV might be used as an early
      indicator of reactivation in children with SLE. MPV seemed to be more accurate
      than ESR, CRP, and C3 for monitoring the disease activity in SLE. 

PMID- 24567245
TI  - Unintentional injury hospitalizations and socio-economic status in areas with a
      high percentage of First Nations identity residents.
AB  - BACKGROUND: Few national studies of hospitalizations due to injuries among the
      First Nations population have been conducted. DATA AND METHODS: Based on
      2004/2005 to 2009/2010 data from the Discharge Abstract Database, this study
      examines associations between unintentional injury hospitalizations, socio
      economic status and location relative to an urban core in Dissemination Areas
      (DAs) with a high percentage of First Nations identity residents versus a low
      percentage of Aboriginal identity residents. RESULTS: Unintentional injury
      hospitalization rates were higher in the less affluent and the most remote DAs.
      When DAs with the same socio-economic status and location were compared, the risk
      of hospitalizations was greater in high-percentage First Nations identity DAs
      relative to low-percentage Aboriginal identity DAs. INTERPRETATION: Socio
      economic conditions and remote location accounted for some, but not all, of the
      differences in unintentional injury hospitalizations between high-percentage
      First Nations identity and low-percentage Aboriginal identity DAs. This suggests
      that characteristics not measured in this analysis--such as environmental,
      behavioural or other factors--play an additional role in DA-level unintentional
      injury hospitalization risk.

PMID- 24567246
TI  - Estimating relative survival for cancer: An analysis of bias introduced by
      outdated life tables.
AB  - BACKGROUND: Relative survival analyses of cancer data often incorporate outdated
      information about expected survival when current information is not readily
      available. The assumption is that any bias introduced into the estimation of
      expected survival, and hence, into the estimate of relative survival, will be
      negligible. However, empirical studies of potential bias have yet to be
      published. DATA AND METHODS: Data are from the Canadian Cancer Registry with
      mortality follow-up through record linkage to the Canadian Vital Statistics Death
      Database. Period method relative survival ratios (RSRs) for 2005-2007 were
      derived using life tables centred on the 2006 Census of Population to estimate
      expected survival. The analysis was repeated using life tables from 5 and 10
      years earlier. RESULTS: Deriving expected survival from life tables 5 years out
      of date resulted in increases in RSRs for all cancers. These increases became
      greater with lengthening survival duration. For example, increases in 1-, 5- and
      10-year RSRs were 0.2, 0.8 and 1.7 percentage units, respectively, for all
      cancers combined. Increases in 5-year survival were highest for prostate (2.0)
      and bladder cancer (1.6); among males (1.2); and among people aged 75 to 99 at
      diagnosis (1.9). Differences were approximately double when life tables 10 years
      out of date were used. INTERPRETATION: The use of historical rather than current
      expected survival data in calculating RSRs for cancer may lead to consequential
      overestimation of survival.

PMID- 24567247
TI  - Suicidality among preadolescent maltreated children in foster care.
AB  - This study sought to determine the prevalence of suicidal ideation, plans, and
      attempts among 515 preadolescent (aged 9-11 years) maltreated children who
      entered foster care within the prior year. Over a quarter (26.4%) of the children
      had a history of suicidality according to their own and/or their caregiver's
      report, 4.1% of whom were imminently suicidal. In bivariate analyses, children at
      higher risk of suicidality tended to be younger, non-Hispanic, abused, and to
      have experienced multiple types of maltreatment, more referrals to child welfare,
      more household transitions, and a longer length of time in foster care. There
      were no gender differences. Multiple regression analyses found physical abuse and
      chronicity of maltreatment to be the most robust predictors of suicidality. It is
      critically important that these high-risk children are screened for suicidality
      before adolescence and that caregivers and professionals are informed of their
      risk status so that they may implement mental health treatment, monitoring, and
      harm reduction measures. 

PMID- 24567248
TI  - Birth prevalence of congenital cytomegalovirus among infants of HIV-infected
      women on prenatal antiretroviral prophylaxis in South Africa.
AB  - BACKGROUND: A high rate of congenital cytomegalovirus (CMV) has been documented
      in human immunodeficiency virus (HIV)-exposed infants in industrialized settings,
      both in the pre- and post-highly active antiretroviral therapy (HAART) era. Only
      limited data on the birth prevalence of congenital CMV among infants of HIV
      infected women on prenatal antiretroviral (ARV) prophylaxis are available from
      sub-Saharan Africa, despite a high prevalence of both infections. We evaluated
      the prevalence of congenital CMV in HIV-exposed infants in the Western Cape,
      South Africa. METHODS: HIV-infected mothers were recruited in the immediate
      postnatal period at a referral maternity hospital between April and October 2012.
      Maternal and infant clinical data and newborn saliva swabs were collected. Saliva
      swabs were assayed by real-time polymerase chain reaction for CMV. Data were
      analyzed using univariate and multivariate logistic regression analyses to
      determine specific demographic, maternal, and newborn characteristics associated
      with congenital CMV. RESULTS: CMV was detected in 22 of 748 newborn saliva swabs
      (2.9%; 95% confidence interval [CI], 1.9%-4.4%). Overall, 96% of mothers used
      prenatal ARV prophylaxis (prenatal zidovudine, 43.9%; HAART, 52.1%). Maternal
      age, gestational age, prematurity (<37 weeks' gestation), type of ARV
      prophylaxis, length of ARV prophylaxis, birth weight, small for gestational age,
      and infant feeding choice were not significantly different between CMV-infected
      and -uninfected infants. Maternal CD4 count <200 cells/MUL during pregnancy was
      independently associated with congenital CMV (adjusted odds ratio, 2.9; 95% CI,
      1.2-7.3). A negative correlation between CMV load in saliva and maternal CD4
      count was observed (r = -0.495, n = 22, P = .019). CONCLUSIONS: The birth
      prevalence of congenital CMV was high despite prenatal ARV prophylaxis, and was
      associated with advanced maternal immunosuppression.

PMID- 24567249
TI  - Mortality associated with seasonal and pandemic influenza and respiratory
      syncytial virus among children <5 years of age in a high HIV prevalence setting-
      South Africa, 1998-2009.
AB  - BACKGROUND: There are few published data describing the mortality burden
      associated with influenza and respiratory syncytial virus (RSV) infection in
      children in low- and middle-income countries and particularly from Africa and
      settings with high prevalence of human immunodeficiency virus (HIV). METHODS: We
      modeled the excess mortality attributable to influenza (seasonal and pandemic)
      and RSV infection by applying Poisson regression models to monthly all
      respiratory and pneumonia and influenza deaths, using national influenza and RSV
      laboratory surveillance data as covariates. In addition, we estimated the
      seasonal influenza- and RSV-associated deaths among HIV-infected and -uninfected
      children using Poisson regression models that incorporated HIV prevalence and
      highly active antiretroviral therapy coverage as covariates. RESULTS: In children
      <5 years of age, the mean annual numbers of seasonal influenza- and RSV
      associated all-respiratory deaths were 452 (8 per 100 000 person-years [PY]) and
      546 (10 per 100 000 PY), respectively. Infants <1 year of age experienced higher
      mortality rates compared with children 1-4 years of age for both influenza (22 vs
      5 per 100 000 PY) and RSV (35 vs 4 per 100 000 PY). HIV-infected compared with
      HIV-uninfected children <5 years of age were at increased risk of death
      associated with influenza (age-adjusted relative risk [aRR], 11.5; 95% confidence
      interval [CI], 9.6-12.6) and RSV (aRR, 8.1; 95% CI, 6.9-9.3) infection. In 2009,
      we estimated 549 (11 per 100 000 PY) all-respiratory influenza A(H1N1)pdm09
      associated deaths among children aged <5 years. CONCLUSIONS: Our findings support
      increased research efforts to guide and prioritize interventions such as
      influenza vaccination and HIV prevention in low- and middle-income countries with
      high HIV prevalence such as South Africa.

PMID- 24567250
TI  - Higher incidence of bone stress injuries with increasing female athlete triad
      related risk factors: a prospective multisite study of exercising girls and
      women.
AB  - BACKGROUND: Identifying the risk factors associated with a bone stress injury
      (BSI), including stress reactions and stress fractures, may aid in targeting
      those at increased risk and in formulating prevention guidelines for exercising
      girls and women. PURPOSE: To evaluate the effect of single or combined risk
      factors as defined by the female athlete triad-a syndrome involving 3
      interrelated spectrums consisting of energy availability, menstrual function, and
      bone mass-with the incidence of BSIs in a multicenter prospective sample of 4
      cohorts of physically active girls and women. STUDY DESIGN: Cohort study; Level
      of evidence, 3. METHODS: At baseline, participants' (N = 259; mean age, 18.1 +/-
      0.3 years) anthropometric characteristics, eating attitudes and behaviors,
      menstrual function, sports participation or exercise activity, and pathological
      weight control behaviors were assessed. Dual-energy x-ray absorptiometry (DXA)
      measured the bone mass of the whole body, total hip, femoral neck, lumbar spine,
      and body composition. Participants were followed prospectively for the occurrence
      of injuries; those injuries confirmed by a physician were recorded. RESULTS:
      Twenty-eight participants (10.8%) incurred a BSI. Forty-six percent of those who
      had >=12 h/wk of purposeful exercise, a bone mineral density (BMD) Z score <-1.0,
      and who exhibited 3 to 4 of the following: BMI <21.0 kg/m2, oligo- or amenorrhea,
      elevated dietary restraint, and/or participation in a leanness sport
      exercise/activity at baseline, incurred a BSI during the prospective study
      period. Single factors significantly (P < .05) associated with the development of
      a BSI included >=12 h/wk of purposeful exercise (14.7%), BMI <21.0 kg/m2 (15.3%),
      and low bone mass (BMD Z score <-1.0; 21.0%). The strongest 2- and 3-variable
      combined risk factors were low BMD (Z score <-1.0) + >=12 h/wk of exercise, with
      29.7% incurring a BSI (odds ratio [OR], 5.1; 95% CI, 2.2-12.1), and >=12 h/wk of
      exercise + leanness sport/activity + dietary restraint, with 46.2% incurring a
      BSI (OR, 8.7; 95% CI, 2.7-28.3). CONCLUSION: In the sample, which included female
      adolescents and young adults participating in competitive or recreational
      exercise activities, the risk of BSIs increased from approximately 15% to 20% for
      significant single risk factors to 30% to 50% for significant combined female
      athlete triad-related risk factor variables. These data support the notion that
      the cumulative risk for BSIs increases as the number of Triad-related risk
      factors accumulates.

PMID- 24567251
TI  - Pediatric sports injuries: a comparison of males versus females.
AB  - BACKGROUND: There is still much that we do not know about differences in sports
      injuries between young male and female athletes and the factors that may increase
      the risk for injuries in this regard. PURPOSE: To describe and compare
      differences between males and females in pediatric sports-related injuries. STUDY
      DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: A retrospective
      chart review was performed using a 5% random sampling (N = 2133) of medical
      records of children aged 5 to 17 years seen over 10 years in a sports medicine
      clinic at a large academic pediatric hospital. Information was collected and
      analyzed on age, sex, height, weight, injury type (overuse vs acute/traumatic),
      location of injury, and sports involvement. RESULTS: Overall, female athletes had
      a higher percentage of overuse injuries (62.5%) compared with traumatic injuries
      (37.5%); the opposite was seen in male athletes (41.9% vs. 58.2%, respectively; P
      < .001). Looking at specific areas of injury, female athletes sustained more
      injuries to the lower extremity (65.8%) and spine (11.3%) as compared with male
      athletes (53.7% and 8.2%, respectively). Male patients had a greater percentage
      of injuries to the upper extremity (29.8%) as compared with female patients
      (15.1%). The type of hip/pelvis injuries differed greatly by sex, with females
      sustaining more overuse (90.9%) and soft tissue injuries (75.3%) versus males,
      who suffered injuries that tended to be traumatic (58.3%) and bony (55.6%) in
      nature. Males were more likely than females to participate in team and
      contact/collision sports. The percentage of females with patellofemoral knee pain
      was approximately 3 times greater than that of males (14.3% vs. 4.0%,
      respectively; P < .001). Males were twice as likely as females to be diagnosed
      with osteochondritis dissecans (8.6% vs. 4.3%, respectively; P < .001) and
      fractures (19.5% vs. 8.2%, respectively; P < .001). The percentage of males and
      females who sustained an anterior cruciate ligament injury was almost equal
      (10.0% and 8.9%, respectively; P = .369). CONCLUSION: Sports injuries in young
      males and females differed by injury type, diagnosis, and body area. These
      results may be related to the referral patterns unique to the division of the
      hospital, including a high number of female dancers. Further investigation is
      required to better understand the injury risk in pediatric male and female
      athletes.

PMID- 24567253
TI  - Back to the bedside: the role of bedside teaching in the modern era.

PMID- 24567252
TI  - Hidden lesions of the posterior horn of the medial meniscus: a systematic
      arthroscopic exploration of the concealed portion of the knee.
AB  - BACKGROUND: Anterior cruciate ligament (ACL) tears are frequently associated with
      meniscal lesions. Despite improvements in meniscal repair techniques, failure
      rates remain significant, especially for the posterior horn of the medial
      meniscus. PURPOSE: To determine whether a systematic arthroscopic exploration of
      the posterior horn of the medial meniscus with an additional posteromedial portal
      is useful to identify otherwise unrecognized lesions. STUDY DESIGN: Case series;
      Level of evidence, 4. METHODS: In a consecutive series of 302 ACL
      reconstructions, a systematic arthroscopic exploration of the posterior horn of
      the medial meniscus was performed. The first stage of the exploration was
      achieved through anterior visualization via a standard anterolateral portal. In
      the second stage, the posterior horn of the medial meniscus was visualized
      posteriorly via the anterolateral portal with the scope positioned deep in the
      notch. In the third stage, the posterior horn was probed through an additional
      posteromedial portal. A chi2 test and logistic regression analysis were performed
      to determine if the time from injury to surgery was associated with the meniscal
      tear pattern. RESULTS: A medial meniscal tear was diagnosed in 125 of the 302
      patients (41.4%). Seventy-five lesions (60%) located in the meniscal body were
      diagnosed at the first stage of the arthroscopic exploration. Fifty lesions
      located in the ramp area were diagnosed: 29 (23.2%) at the second stage and 21
      lesions (16.8%) at the third stage after minimal debridement of the superficial
      soft tissue layer. The latter type of lesion is called a "hidden lesion."
      Altogether, the prevalence of ramp lesions in this population was 40%. Meniscal
      body lesions (odds ratio, 2.6; 95% confidence interval, 1.18-5.18; P < .02) were
      found to be significantly correlated with a longer delay between injury and
      surgery. CONCLUSION: Posterior visualization and posteromedial probing of the
      posterior horn of the medial meniscus can help in discovering a higher rate of
      lesions that could be easily missed through a standard anterior exploration. In
      numerous cases, these lesions were "hidden" under a membrane-like tissue and were
      discovered after minimal debridement through a posteromedial portal.

PMID- 24567254
TI  - Reflections on having a 'calling' as a medical doctor.

PMID- 24567255
TI  - Effects of Kaixin Jieyu Decoction () on behavior, monoamine neurotransmitter
      levels, and serotonin receptor subtype expression in the brain of a rat
      depression model.
AB  - OBJECTIVE: To determine the mechanisms underlying the anti-depressant effects of
      Kaixin Jieyu Decoction (, KJD) by investigating the effects of KJD on behavior,
      monoamine neurotransmitter levels, and serotonin (5-HT) receptor subtype
      expression in the brain in a rat model of depression. METHODS: The rat depression
      model was established using chronic unpredictable mild stress (CUMS). Forty-eight
      Sprague Dawley rats were randomly divided into control, depression model (CUMS),
      CUMS+KJD (7.7 g/kg(-1).d(-1) of crude drug), and CUMS+fluoxetine (2.4 mg/kg(
      1).d(-1)) groups (n=12 in each group), and the treatments lasted for 21 days. We
      regularly evaluated body weight, sucrose consumption, and horizontal and vertical
      activity scores in open-field tests. The content of the monoamine
      neurotransmitters 5-HT, norepinephrine (NE), and dopamine (DA) and the DA
      metabolite homovanillic acid in the cerebral cortex, and 5-HT1A and 5-HT2A
      receptor mRNA in the cerebral cortex and the hippocampus, were determined
      respectively by high-performance liquid chromatography-coularray electrochemical
      detector and real-time polymerase chain reaction. RESULTS: Compared with the
      control group, CUMS rats showed a variety of depression-like behavioral changes,
      including a significant reduction in body weight, sucrose consumption, and
      horizontal and vertical activity scores in open-field tests (P<0.05 or P<0.01),
      and a significant decrease in 5-HT and NE levels and 5-HT2A receptor mRNA
      expression. In contrast, they showed a significant increase in 5-HT1A receptor
      mRNA expression in the cerebral cortex. In the hippocampus, 5-HT1A receptor mRNA
      expression was lower whereas 5-HT2A receptor mRNA expression was higher than in
      the control group (P<0.05 or P<0.01). Treatment with KJD or fluoxetine partially
      attenuated these changes (P<0.05 or P<0.01). CONCLUSION: KJD could normalize the
      levels of 5-HT and NE and adjust the balance of 5-HT1A and 5-HT2A receptor
      expression in rat cerebrum, and this may be one of mechanisms of antidepressant
      effects of KJD.

PMID- 24567258
TI  - Basal cell carcinoma of the axilla: review of the world literature.
AB  - Basal cell carcinoma (BCC) of the axilla is rare; indeed, 70 axillary BCCs have
      been described in 69 patients. Using the PubMed database, an extensive literature
      search was performed on BCC, axilla, and axillary. Relevant papers were reviewed
      and the characteristics of individuals with BCC of the axilla were summarized.
      The calculated prevalence of axillary BCC was 0.17%. They occurred predominantly
      in Caucasians. The majority of patients had no obvious BCC-associated risk
      factors. They were observed 1.2 times more often in men than in women and twice
      as often in the right axilla than the left axilla. They frequently presented as
      an asymptomatic nodule; however, associated features have included elongation of
      the tumor along the axillary skin lines, ulceration, and pigmentation. The
      axillary tumor was typically associated with either the superficial or the
      nodular histologic subtype of BCC. The prognosis for these patients was usually
      excellent following complete removal or destruction of the tumor. In conclusion,
      axillary BCC is a rare clinical variant of this type of skin cancer that usually
      presents as an asymptomatic nodule in an individual who does not have any
      traditional risk factors for this malignancy. The cancer was typically associated
      with a non-aggressive histologic subtype. Recurrence or metastasis was uncommon
      following treatment of the primary tumor.

PMID- 24567257
TI  - Neuroethology of male courtship in Drosophila: from the gene to behavior.
AB  - Neurogenetic analyses in the fruit fly Drosophila melanogaster revealed that
      gendered behaviors, including courtship, are underpinned by sexually dimorphic
      neural circuitries, whose development is directed in a sex-specific manner by
      transcription factor genes, fruitless (fru) and doublesex (dsx), two core members
      composing the sex-determination cascade. Via chromatin modification the Fru
      proteins translated specifically in the male nervous system lead the fru
      expressing neurons to take on the male fate, as manifested by their male-specific
      survival or male-specific neurite formations. One such male-specific neuron
      group, P1, was shown to be activated when the male taps the female abdomen.
      Moreover, when artificially activated, P1 neurons are sufficient to induce the
      entire repertoire of the male courtship ritual. These studies provide a
      conceptual framework for understanding how the genetic code for innate behavior
      can be embodied in the neuronal substrate. 

PMID- 24567259
TI  - Forty years of haematopoietic stem cell transplantation: a review of the Basel
      experience.
AB  - The purpose of this study was to examine changes in haematopoietic stem cell
      transplant (HSCT) characteristics and outcome in our combined paediatric and
      adult programme over the past four decades, since its implementation in 1973. The
      total number of transplant procedures rose from 109 in the first decade (1973-82)
      to 939 in the last decade (2003-12). Transplant characteristics changed
      significantly over time: patient age increased, peripheral blood largely replaced
      bone marrow as stem cell source, unrelated donors became an alternative to
      matched siblings, and patients are increasingly transplanted in more advanced
      disease stages. Advances such as improved supportive care and histocompatibility
      typing resulted in a steady decrease of transplant-related mortality after
      allogeneic HSCT (43% in the first decade, 22% in the last decade). Despite this,
      unadjusted survival rates were stable in the last three decades for allogeneic
      HSCT (approximately 50% 5-year survival) and in the last two decades for
      autologous HSCT (approximately 60% 5-year survival). After adjustment for
      covariates such as donor type, age and stage, the relative risk of treatment
      failure continuously dropped (for allogeneic HSCT: first decade 1.0, second
      decade 0.58, third decade 0.51, last decade 0.41). Collectively, these data
      suggest that improvements in peri- and post-transplant care have allowed
      considerable extension of transplant indications without having a negative impact
      on outcome.

PMID- 24567261
TI  - The cost effectiveness of biologic therapy for the treatment of chronic plaque
      psoriasis in real practice settings in Italy.
AB  - BACKGROUND AND OBJECTIVES: Biologic therapies are considered to be cost effective
      by leading Health Technology Assessment (HTA) agencies and, therefore, eligible
      for reimbursement by public health services. However, biologic therapies entail
      sizable incremental costs and, besides, have a considerable financial impact that
      in Italy amounts to 13.7 % of the national health service's pharmaceutical
      expenditure. In the reimbursability decision process, an important role is played
      by both the drug efficacy data observed in pre-licensing RCTs and the economic
      modelling assumptions, as they give evidence on cost effectiveness. The
      administration of therapies in real practice settings is likely to produce a
      significant deviation from the results predicted by the models, theoretically
      outweighing the assumption on which the decision process is founded. This is a
      matter of concern for public health services and, consequently, an interesting
      topic to investigate. METHODS: To overcome the lack of knowledge concerning the
      actual cost effectiveness of biologic therapies for the treatment of plaque
      psoriasis in the clinical practice setting in Italy, an observational study was
      conducted in 12 specialist centres on patients switching to biologic therapy
      within a 6-month enrolment window. RESULTS: The study confirms in clinical
      practice the efficacy of the switch to biologic therapies, analysed using a
      number of clinical [Psoriasis Area and Severity Index (PASI), pain visual
      analogue scale (VAS) and itching VAS] and quality-of-life parameters. A general
      health-related quality of life (HR-QOL) improvement, with a 0.23 quality-adjusted
      life-year (QALY) mean gain per patient, has been reported in the 6-month
      observation period. The direct medical costs to treat plaque psoriasis with
      biologic therapies amount to <euro>15,073.7 per year (prior to their enrolment,
      the same patients cost <euro>2,166.2 on an annual basis). After the switch to
      biologic agents, the cost per QALY during the first year of treatment amounts to
      <euro>28,656.3. CONCLUSION: At least in the short-term, the clinical practice of
      the specialised Italian centres taking part in the study confirms that switching
      patients to a biologic drug produces an incremental cost-effectiveness ratio
      comparable with the values predicted by the HTA bodies.

PMID- 24567263
TI  - Drift, evolution, and divergence in biologics and biosimilars manufacturing.
AB  - Biological medicines (biologics) are produced in living cells and purified in
      complex, multi-step processes. Compared with chemically synthesized small
      molecule drugs, biologics are more sensitive to changes in manufacturing
      conditions. Process and product consistency should be founded on rigorous design
      and control of manufacturing processes, but consistency is ultimately ensured
      through robust quality systems. Even a minor change in any component of a quality
      system could lead to product drift, evolution, and divergence, which may impact
      the quality, safety, efficacy, and/or interchangeability of biologics. Unintended
      or unexplained deviations in manufacturing processes can lead to excursions in
      product attributes (i.e., drift). Well-managed quality systems can help detect
      and mitigate drift. Occasionally, quality attributes could shift outside of
      established acceptable ranges as the result of a known manufacturing change
      (defined here as evolution). Such changes should be studied extensively for
      effects on product safety and efficacy. With the advent of biosimilars, similar
      biologics will be produced by multiple manufacturers with different quality
      systems. Different patterns of product drift and evolution could contribute, over
      time, to clinically meaningful differences among biologics, including among
      originator products across regions and among originator products and biosimilar
      products, a process defined here as divergence. Manufacturers and policymakers
      can minimize the potential impact of divergence by establishing robust
      pharmacovigilance systems; requiring distinguishable names for all biologics,
      including both originator products and biosimilars; adhering to high standards
      for designations of interchangeability; and ensuring that patient medical records
      accurately reflect the specific biologic dispensed, especially if the biologic
      could be sourced from multiple manufacturers.

PMID- 24567262
TI  - Attenuation of carbon tetrachloride-induced hepatic injury with curcumin-loaded
      solid lipid nanoparticles.
AB  - BACKGROUND AND OBJECTIVES: Curcumin, an established pleiotropic agent, has
      potential for hepatoprotection owing to its powerful antioxidant, anti
      inflammatory, and antifibrogenic properties. However, its poor bioavailability
      limits its use in therapeutics. In this study, we aimed to package curcumin into
      solid lipid nanoparticles (C-SLNs) to improve its bioavailability and compare the
      efficacy of C-SLNs with that of free curcumin and silymarin, a well-established
      hepatoprotectant in clinical use, against carbon tetrachloride (CCl4)-induced
      hepatic injury in rats, post-induction. A self-recovery group to which no
      treatment was given was also employed for quantifying self-healing of hepatic
      tissue, if any. MATERIAL AND METHODS: C-SLNs (particle size 147.6 nm), prepared
      using a microemulsification technique, were administered to rats post-treatment
      with CCl4 (1 ml/kg body weight [BW] twice weekly for 2 weeks, followed by 1.5
      ml/kg BW twice weekly for the subsequent 2 weeks). The extent of liver damage and
      repair in terms of histopathology and levels of alanine aminotransferase (ALT),
      aspartate aminotransferase (AST), oxidative stress markers (malondialdehyde,
      superoxide dismutase, and reduced glutathione) and a pro-inflammatory response
      marker, tumor necrosis factor (TNF)-alpha, were determined in both the CCl4 group
      and the treatment groups. RESULTS: C-SLNs (12.5 mg/kg) significantly (p < 0.001
      0.005) attenuated histopathological changes and oxidative stress, and also
      decreased induction of ALT, AST, and TNF-alpha in comparison with free curcumin
      (100 mg/kg), silymarin (25 mg/kg), and self-recovery groups. CONCLUSION: Curcumin
      could be used as a therapeutic agent for hepatic disorders, provided it is loaded
      into a suitable delivery system.

PMID- 24567260
TI  - Dysregulation of microRNAs and their association in the pathogenesis of T-cell
      lymphoma/leukemias.
AB  - MicroRNAs (miRNAs) are non-coding regulatory RNAs consisting of 20-24
      nucleotides. Over 4,500 miRNAs have been identified in humans, and it is known
      that nearly all human protein-encoding genes can be controlled by miRNAs in both
      healthy and malignant cells. Abnormal miRNA expression is known to occur in many
      cancers, including in malignant lymphomas (MLs). Detailed genome-wide miRNA
      expression analysis has been performed in various ML subtypes, and these analyses
      have led to the discovery of subtype-specific miRNA alterations. Actually, in B
      cell lymphomas, several miRNAs have been used as prognostic markers, and their
      targets are for new agents for ML therapy. Successful studies for delineating
      miRNA functions in B-cell lymphomas lead us to hypothesize that miRNA
      dysregulation may also be deeply associated with the pathogenesis of T-cell
      lymphomas. Indeed, studies for delineating essential miRNAs have been conduced
      against comparatively well-defined T-cell lymphoma entities. In this review, we
      describe several key miRNAs and their targets in distinct T-cell lymphoma subsets
      and their roles in their pathogenesis, studies of which will lead to new
      therapeutic strategies against T-cell lymphomas. 

PMID- 24567264
TI  - Purification, characterization and plasma half-life of PEGylated soluble
      recombinant non-HA-binding CD44.
AB  - BACKGROUND AND OBJECTIVES: The aim of this study was to increase the serum half
      life of recombinant CD44 hyaluronan (HA) binding domain by PEGylation. We have
      previously found that recombinant soluble CD44 HA binding domain (CD44HABD) and
      its non-HA-binding triple mutant CD44HABD(R41AY78SY79S) (CD44-3MUT) inhibits
      angiogenesis and subcutaneous tumor growth. However, this ~12 kDa recombinant
      protein displays a high serum clearance rate. METHODS: Here, we report the
      purification of monomeric CD44-3MUT from urea solubilized inclusion bodies using
      weak anion exchange chromatography and gel filtration. To increase the serum
      residence time of CD44-3MUT we PEGylated the resulting protein using 20 kDa
      methoxy-PEG-propionaldehyde. RESULTS: PEGylation of CD44-3MUT prolonged its in
      vivo serum half-life about 70-fold from 0.03 to 1.8 hours. Along with extended
      plasma residence time, PEGylation also increased the systemic exposure. By cell
      impedance assay we confirmed that PEGylated CD44-3MUT maintained its in vitro
      function. The results from the impedance assay additionally demonstrate that the
      CD44-3MUT effect on endothelial cells is mediated by vimentin. CONCLUSIONS: In
      summary, we have developed a purification protocol for large-scale production of
      CD44-3MUT and generated a PEGylated form of CD44-3MUT. HA binding domain of
      CD44(CD44HABD) and its modified non-HA binding form (CD44-3MUT) inhibit
      angiogenesis and tumor growth in vivo without disturbing HA-binding functions.
      CD44-3MUT has been PEGylated for use as a new type of anti-angiogenic human drug.
      PEGylation of CD44-3MUT improved pharmacokinetic properties but retains its
      functional activity.

PMID- 24567265
TI  - Targeting the PI3K/Akt/mTOR pathway in malignancy: rationale and clinical
      outlook.
AB  - The phosphatidylinositol 3-kinase (PI3K) pathway, including major downstream
      effectors Akt and mammalian target of rapamycin (mTOR), plays a critical role in
      malignant transformation and subsequent processes of growth, proliferation, and
      metastases. Not surprisingly, the PI3K/Akt/mTOR pathway has emerged as an
      attractive drug target and numerous agents directed against various elements of
      the pathway are currently in clinical development. While early clinical trials
      with the first generations of these agents have shown limited single-agent
      efficacy, efforts are now focused on the development of more specific inhibitors,
      patient selection strategies, and combinational approaches. In this review, we
      discuss the PI3K/Akt/mTOR pathway in cancer, the rationale for its emergence as a
      therapeutic target, and progress thus far in the clinical development of
      inhibitors targeting its various elements.

PMID- 24567266
TI  - Medical students' career expectations and interest in opting for a surgical
      career.
AB  - BACKGROUND: Whilst surgery will face an imminent workforce shortage, an
      increasing majority of students decide against a surgical career. This study
      evaluated the current career expectations of medical students and tested a hands
      on virtual reality (VR) intervention as a tool to increase their interest in
      surgery. METHODS: Randomly selected medical students of the University of Basel
      received a short questionnaire to rank their interest in five different
      postgraduate working environments prior to a lecture. After the lecture they
      participated in a hands-on VR demonstration. Thereafter an online questionnaire
      regarding workplace expectations, surgery and VR was sent to the students.
      RESULTS: The online questionnaire response rate was 87% (225/258). Before using
      the VR intervention, a nonsurgical career was preferred by the majority of
      students, followed by a surgical career, cross-disciplinary specialties, research
      and, finally, nonclinical work. Surgery (n = 99, 44%) and emergency medicine (n =
      111, 49%) were rated as incompatible with a good work-life balance. Further
      drawbacks to surgery were apprehension of competitive mentality, unclear career
      perspectives and longer working hours. The VR intervention had limited impact on
      re-ranking the five working sectors and slightly increased the students' interest
      in surgery. CONCLUSION: Students' work environment expectations, their declining
      interest in a surgical career and the increasing need for surgeons represent
      challenges for surgical societies to address, in order to improve the
      attractiveness of surgery amongst students. VR sessions may be integrated as part
      of the actions required to improve students' interest in a surgical career and
      should be further evaluated within controlled study designs.

PMID- 24567267
TI  - Is the osteopathic medical profession prepared for a radiologic or nuclear
      incident?

PMID- 24567268
TI  - Osteopathic manipulative treatment in tarsal somatic dysfunction: a case study.

PMID- 24567269
TI  - Preliminary findings on the use of osteopathic manipulative treatment: outcomes
      during the formation of the practice-based research network, DO-Touch.NET.
AB  - CONTEXT: Few studies have assessed the use of osteopathic manipulative treatment
      (OMT) and subsequent patient-reported outcomes. OBJECTIVE: To assess the current
      use of OMT and associated patient-reported outcomes. DESIGN: A retrospective
      medical record review and a prospective observational study. SETTING: Two
      university-based sites and their clinics associated with the practice-based
      research network DO-Touch.NET. PARTICIPANTS: Patients aged 18 years or older who
      received OMT. MAIN OUTCOME MEASURES: Medical records from 2007 were
      retrospectively reviewed to identify conditions being managed with OMT. From 2008
      to 2010, patients were recruited before seeing their physicians. Questionnaires
      were distributed to patients and physicians, and information including
      demographics, chief complaints, symptom severity, current and past treatments,
      interference of symptoms with quality of life, physical examination findings,
      diagnoses, OMT performed, and immediate patient response to OMT was collected. A
      subset of patients provided data on symptom severity and frequency and other
      treatments daily for the 7 days after OMT. On day 7, symptom interference with
      quality of life was reassessed. RESULTS: Retrospective data were collected from
      2569 office visits, and prospective data were collected from 299 office visits
      (patient age range, 18-93 years). In the medical record review, 17 of the top 25
      diagnoses (68%) were related to musculoskeletal conditions. In the prospective
      study, 18 of the top 24 medical diagnoses (75%) were related to musculoskeletal
      conditions. Immediately after OMT, patients at 271 of 296 office visits (92%)
      felt better or much better; those at 5 (<2%) felt worse. After 7 days, patients
      at 126 of 175 office visits (72%) felt better or much better, and those at 10
      (6%) felt worse. Average and worst symptom severity decreased until post-OMT days
      4 and 5, respectively, when severity leveled off. There was decreased
      interference of symptoms with quality of life from before OMT to 7 days after OMT
      in usual/general activities, sleep, mood, and relationships (all P<=.05).
      CONCLUSION: These preliminary results suggest that for adults, OMT is
      predominantly used for managing musculoskeletal pain conditions and is effective
      for short-term symptom relief. Continued surveillance of DO-Touch.NET member
      practice outcomes may help identify priorities for osteopathic research and
      define evidence-based standards for OMT practice and training.

PMID- 24567270
TI  - Vestibular dysfunction in patients with chronic pain or underlying neurologic
      disorders.
AB  - CONTEXT: Individuals with vestibular dysfunction are at increased risk for
      falling. In addition, vestibular dysfunction is associated with chronic pain,
      which could present a serious public health concern as approximately 43% of US
      adults have chronic pain. OBJECTIVE: To assess the incidence of vestibular
      dysfunction in patients receiving medication for chronic, noncancer pain or other
      underlying neurologic disorders and to determine associated follow-up therapeutic
      and diagnostic recommendations. METHODS: The authors conducted a retrospective
      medical record review of consecutive patients who were treated in their private
      neuroscience practice with medications for chronic pain or underlying neurologic
      disorders in 2011. All patients underwent a series of tests using
      videonystagmography for the assessment of vestibular function. Test results and
      recommendations for therapy and additional testing were obtained. RESULTS:
      Medical records of 124 patients (78 women, 46 men) were reviewed. Vestibular
      deficits were detected in 83 patients (66.9%). Patient ages ranged from 29
      through 72 years, with a mean age of 50.7 years for women and 52.5 years for men.
      Physician-recommended therapy and follow-up testing were as follows: 32 patients
      (38.6%), neurologic examination and possible magnetic resonance (MR) imaging or
      computed tomography (CT) of the brain; 26 patients (31.3%), vestibular
      rehabilitation therapy only; 22 patients (26.5%), vestibular and related balance
      function rehabilitation therapy, further neurologic examination, and possible MR
      imaging or CT; 2 patients (2.4%), balance-function rehabilitation therapy and
      specialized internal auditory canal high-magnification MR imaging or CT to assess
      for acoustic neuroma; and 1 patient (1.2%), specialized internal auditory canal
      high-magnification MR imaging or CT to evaluate for possible intracanalicular
      acoustic neuroma. CONCLUSION: Patients being treated with medications for
      chronic, noncancer pain or other underlying neurologic disorders may have a
      higher-than-average incidence of vestibular dysfunction. Baseline assessment and
      monitoring of the vestibular apparatus may be indicated for these patients.

PMID- 24567271
TI  - Qualitative evaluation of osteopathic manipulative therapy in a patient with
      gastroesophageal reflux disease: a brief report.
AB  - CONTEXT: Gastroesophageal reflux disease (GERD) is a chronic condition that
      affects a growing number of people and is currently among the most common
      disorders seen in clinical practice. OBJECTIVE: To develop a protocol for the
      management of GERD with osteopathic manipulative therapy (OMTh) applied to the
      diaphragm and esophagus, and to evaluate the protocol's effectiveness using the
      quality of life scale (QS-GERD) for the disease. METHODS: In this single-blinded
      prospective study, an OMTh protocol focusing on the diaphragm and esophagus was
      applied to a single patient, who had received a diagnosis of GERD 4 years
      previously. Outcomes were measured using the QS-GERD, which has a total possible
      score ranging from 0 to 45 (the lower the score, the better the quality of life)
      and a level of satisfaction from very satisfied to incapacitated. The OMTh
      protocol was applied at 3 sessions (initial session, second session 1 week after
      the first, and third session 2 weeks after the second), and the patient completed
      the QS-GERD 4 times (before the first session, before the third session, and 2
      and 4 weeks after the third session). RESULTS: The OMTh protocol was administered
      without adverse events, and the patient reported positive outcomes after the
      third session. The QS-GERD showed a score improvement from 13 of 45 to 4 of 45.
      CONCLUSION: The results in the present report show that OMTh applied to the
      diaphragm and esophagus may improve symptoms of GERD and should be added to the
      somatovisceral approach to the care of patients with this condition.

PMID- 24567272
TI  - Management of ionizing radiation injuries and illnesses, part 1: physics,
      radiation protection, and radiation instrumentation.
AB  - Ionizing radiation injuries and illnesses are exceedingly rare; therefore, most
      physicians have never managed such conditions. When confronted with a possible
      radiation injury or illness, most physicians must seek specialty consultation.
      Protection of responders, health care workers, and patients is an absolute
      priority for the delivery of medical care. Management of ionizing radiation
      injuries and illnesses, as well as radiation protection, requires a basic
      understanding of physics. Also, to provide a greater measure of safety when
      working with radioactive materials, instrumentation for detection and
      identification of radiation is needed. Because any health care professional could
      face a radiation emergency, it is imperative that all institutions have emergency
      response plans in place before an incident occurs. The present article is an
      introduction to basic physics, ionizing radiation, radiation protection, and
      radiation instrumentation, and it provides a basis for management of the
      consequences of a radiologic or nuclear incident. 

PMID- 24567273
TI  - The "doctor of osteopathy": expanding the scope of practice.
AB  - This article-the third in a 6-part series-examines the status of the DO degree in
      the first 3 decades of the 20th century. This time was an era when osteopathic
      practitioners established other colleges, developed state and national
      organizations, upgraded the length and breadth of curricula, and sought to secure
      licensure laws commensurate with their expanded education. During this period,
      osteopathic practitioners debated whether the DO degree was the most appropriate
      degree for their colleges to award or whether the MD degree alone or in
      conjunction with the DO degree better signified to lawmakers and the public their
      expanded academic training. At the end of this period it appeared likely that the
      DO degree would continue to be the sole designation by which osteopathic
      physicians would identify themselves in continuing their fight to obtain further
      legal rights and privileges. 

PMID- 24567274
TI  - Digoxin as a treatment for patients with idiopathic intracranial hypertension.
AB  - Idiopathic intracranial hypertension (IIH)-sometimes called pseudotumor cerebri
      is a neurologic condition distinguished by any of the following symptoms:
      headache, increased cerebrospinal fluid pressure, papilledema, vision loss,
      diplopia, tinnitus, deafness, nausea and vomiting, or sixth nerve palsy. Medical
      and surgical management options are available for patients with IIH. The authors
      report a case of IIH that was successfully resolved with digoxin after standard
      avenues of therapy were exhausted. 

PMID- 24567275
TI  - Longus colli tendinitis.

PMID- 24567276
TI  - A different view of the Middle East.

PMID- 24567277
TI  - Tiotropium use in pediatric patients with asthma or chronic cough: a case series.

PMID- 24567278
TI  - Long-term efficacy of OROS(r) hydromorphone combined with pregabalin for chronic
      non-cancer neuropathic pain.
AB  - BACKGROUND AND OBJECTIVES: Treatment for chronic non-cancer neuropathic pain can
      be complicated by side effects and drug interactions. Combining opioid analgesics
      and calcium channel modulators may overcome these and improve efficacy. The
      objective of the present study was to evaluate the efficacy and safety of OROS(r)
      hydromorphone combined with pregabalin in patients with chronic non-cancer
      neuropathic pain. METHODS: This retrospective observational study was conducted
      on clinical records from patients aged >=18 years with chronic non-cancer
      neuropathic [>4 on the Douleur Neuropathique en 4 questions (DN4) scale] pain of
      >=6 months duration, with severe intensity [>4 on the Numerical Rating Scale
      (NRS); range 0-10], who attended all visits and had >=12 months of follow-up at
      the Tor Vergata University Polyclinic Hospital, from November 2008 to February
      2011. Patients received an oral combination of OROS(r) hydromorphone and
      pregabalin. Pain was evaluated at each visit (months 1, 3, 6, 9, and 12) using
      the NRS and DN4 scale; Patients' Global Impression of Change (PGIC) was
      administered at months 1, 6, and 12. Dosage and side effects were recorded at
      each visit. RESULTS: Of 1,292 patients (32 % men, mean +/- SD age 67.6 +/- 11.9
      years), 1,126 attended all visits. Seventeen percent (n = 224) had purely
      neuropathic pain. Initial mean dosage was 6.06 +/- 2.00 mg/day for OROS(r)
      hydromorphone, 113.02 +/- 21.94 mg/day for pregabalin. Dosages increased up to
      month 6, and returned to near initial dosages at month 12 (range 4-120 mg/day for
      OROS(r) hydromorphone; 75-600 mg/day for pregabalin). NRS pain scores (mean +/-
      standard deviation) were 7.25 +/- 1.34 at baseline and 1.85 +/- 1.36 at 12 months
      (p < 0.0001); DN4 scores were 6.19 +/- 1.65 at baseline, reduced to 1.84 +/- 1.25
      at 12 months (p < 0.0001), reductions of 74.4 and 70.2 %, respectively. More than
      90 % of patients had a >=50 % score reduction on both scales after 12 months. The
      PGIC scale showed that >75 % of patients felt improvement at 1 month, increasing
      to 91 % and 93 % at 6 and 12 months. The incidence of side effects was similar
      between elderly (aged >65 years) and younger subjects; there were no cases of
      addiction. CONCLUSIONS: The OROS(r) hydromorphone and pregabalin combination was
      efficacious for chronic non-cancer neuropathic pain and well tolerated, providing
      significant pain reduction without the risk of addiction and with a good
      tolerability profile, regardless of age.

PMID- 24567279
TI  - Pharmacokinetics of lacosamide and omeprazole coadministration in healthy
      volunteers: results from a phase I, randomized, crossover trial.
AB  - BACKGROUND: The antiepileptic drug lacosamide has a low potential for drug-drug
      interactions, but is a substrate and moderate inhibitor of the cytochrome P450
      (CYP) enzyme CYP2C19. OBJECTIVE: This phase I, randomized, open-label, two-way
      crossover trial evaluated the pharmacokinetic effects of lacosamide and
      omeprazole coadministration. METHODS: Healthy, White, male volunteers (n = 36)
      who were not poor metabolizers of CYP2C19 were randomized to treatment A (single
      dose 40 mg omeprazole on days 1 and 8 together with 6 days of multiple-dose
      lacosamide [200-600 mg/day] on days 3-8) and treatment B (single doses of 300 mg
      lacosamide on days 1 and 8 with 7 days of 40 mg/day omeprazole on days 3-9) in
      pseudorandom order, separated by a >= 7-day washout period. Area under the
      concentration-time curve (AUC) and peak concentration (C(max)) were the primary
      pharmacokinetic parameters measured for lacosamide or omeprazole administered
      alone (reference) or in combination (test). Bioequivalence was determined if the
      90 % confidence interval (CI) of the ratio (test/reference) fell within the
      acceptance range of 0.8-1.25. RESULTS: The point estimates (90 % CI) of the ratio
      of omeprazole + lacosamide coadministered versus omeprazole alone for AUC (1.098
      [0.996-1.209]) and C(max) (1.105 [0.979-1.247]) fell within the acceptance range
      for bioequivalence. The point estimates (90 % CI) of the ratio of lacosamide +
      omeprazole coadministration versus lacosamide alone also fell within the
      acceptance range for bioequivalence (AUC 1.133 [1.102-1.165]); C(max) 0.996
      (0.947-1.047). CONCLUSION: Steady-state lacosamide did not influence omeprazole
      single-dose pharmacokinetics, and multiple-dose omeprazole did not influence
      lacosamide single-dose pharmacokinetics.

PMID- 24567280
TI  - Cost effectiveness of fesoterodine and tolterodine for the treatment of
      overactive bladder with urge urinary incontinence in Spain and Finland.
AB  - BACKGROUND: Overactive bladder is a prevalent condition worldwide that is
      associated with a considerable burden, both on the patient and on society.
      OBJECTIVE: Our objective was to assess the economic value of fesoterodine
      compared with tolterodine extended release (ER) for the treatment of overactive
      bladder (OAB) with urge urinary incontinence (UUI) in Spain and Finland. METHODS:
      A decision-tree economic model estimated the 52-week costs and quality-adjusted
      life-years (QALYs) of OAB/UUI patients initiating treatment with fesoterodine 4
      mg/day or tolterodine ER. Individuals were evaluated for treatment response (UUI
      fewer than one episode/day) and persistence at weeks 4, 12, and 24. Titration
      from fesoterodine 4 mg/day to 8 mg/day was permitted at week 4. At week 12, non
      responders discontinued treatment permanently. Efficacy, discontinuation, and
      utility data were derived from four clinical trials of fesoterodine. OAB-related
      costs, including physician visits, laboratory tests, incontinence pads, and
      comorbidities (fracture, skin infection, urinary tract infections, depression,
      and nursing home) were also included. RESULTS: A total of 19.5 % and 18.0 % of
      fesoterodine and tolterodine ER patients remained on treatment until week 52,
      respectively. QALYs were higher with fesoterodine than tolterodine ER (0.762 vs.
      0.760). In Spain, fesoterodine treatment had higher total costs than (generic)
      tolterodine ER (?6,697 vs. 6,597), resulting in a cost of ?15,633/QALY gained. In
      Finland, fesoterodine was cost saving relative to (non-generic) tolterodine ER
      (?7,885 vs. 8,024). Sensitivity analysis confirmed that these findings were
      robust to the expected price decrease for generic tolterodine ER in Finland.
      CONCLUSION: Fesoterodine is cost effective or cost saving relative to tolterodine
      ER for the treatment of OAB with UUI in two European countries. Payers and
      prescribers should consider a broad scope of costs to make informed cost
      conscious choices of antimuscarinic treatment.

PMID- 24567281
TI  - Evaluation of quality of life following placement of self-expanding plastic
      stents as a bridge to surgery in patients receiving neoadjuvant therapy for
      esophageal cancer.
AB  - PURPOSE: To determine whether self-expanding plastic stent (SEPS) placement
      significantly improves quality of life and maintains optimal nutrition while
      allowing full-dose neoadjuvant therapy (NAT) in patients with esophageal cancer.
      PATIENTS AND METHODS: A prospective, dual-institution, single-arm, phase II
      (http://ClinicalTrials.gov: NCT00727376) evaluation of esophageal cancer patients
      undergoing NAT prior to resection. All patients had a self-expanding polymer
      stent placed prior to NAT. The European Organisation for Research and Treatment
      of Cancer QLQ-C30 and QLQ-OG25, Functional Assessment of Cancer Therapy-Anorexia,
      and Functional Assessment of Cancer Therapy-General surveys were administered
      prior to stenting, within 1 week post-stent placement, and at the completion of
      neoadjuvant therapy. RESULTS: Fifty-two patients were enrolled; 3 (5.8%) had
      stent migrations requiring replacement. There were no instances of esophageal
      erosion or perforation. All patients received some form of neoadjuvant therapy.
      Thirty-six (69%) received chemoradiation; 34 (93%) of these patients received the
      planned dose of chemotherapy, and 27 (75%) received the full planned dose of
      radiotherapy. There were 16 (31%) patients receiving chemotherapy alone; 12 (74%)
      of patients in the chemotherapy-alone group completed the planned dose of
      therapy. CONCLUSION: Placement of SEPS appears to provide significant improvement
      in quality of life related to dysphagia and eating restriction in patients with
      esophageal cancer undergoing neoadjuvant therapy. Consideration of SEPS instead
      of percutaneous feeding tube should be initiated as a first line in dysphagia
      palliation and NAT nutritional support.

PMID- 24567282
TI  - The European Cancer Patient's Bill of Rights: action steps for success.

PMID- 24567284
TI  - [Tract sealing techniques in percutaneous nephrolitholapaxy].
AB  - Since the introduction of the percutanous nephrolitholapaxy (PNL), the
      instruments as well as the technique have experienced a tremendous modification.
      The miniaturisation of the instruments has led to a decreased hospital stay,
      reduced analgetic use as well as an extension of the indication for PNL. A
      nephrostomy tube was normally inserted to prevent urinoma and to provoke renal
      haemostasis. In 1997, the necessity for the regular use of a nephrostomy tube was
      first questioned. In a prospective study, the nephrostomy tube was successfully
      omitted in 50 selected patients. Since then, increasingly, the nephrostomy tube
      is omitted. Alternatively, different haemostatic substances are used for renal
      tract closure. The necessity for the use of these agents is still unclear. 

PMID- 24567283
TI  - Clinical features, management, and prognosis of an international series of 161
      patients with limited-stage diffuse large B-cell lymphoma of the bone (the IELSG
      14 study).
AB  - INTRODUCTION: The clinical features, management, and prognosis of stage I-II
      diffuse large B-cell lymphoma of the bone (PB-DLBCL) included in an international
      database of 499 lymphoma patients with skeletal involvement were reviewed.
      METHODS: HIV-negative patients (n = 161) with diffuse large B-cell lymphoma of
      the bone (PB-DLBCL) after complete staging workup were considered. The primary
      objective of this study was to identify the most effective treatment modality;
      the secondary objectives were to define the contribution of irradiation fields
      and doses and the pattern of relapse. RESULTS: Median age was 55 years (range, 18
      99 years), with a male/female ratio of 1:2; 141 (87%) patients had stage I, 14
      (9%) had B symptoms, 37 (23%) had bulky lesion, 54 (33%) showed elevated lactate
      dehydrogenase serum levels, and 25 (15%) had fracture. Thirteen (8%) patients
      received chemotherapy alone, 23 (14%) received radiotherapy alone, and 125 (78%)
      received both treatments. The response to the first-line treatment was complete
      in 131 of 152 assessed patients (complete response rate, 86%; 95% confidence
      interval [CI], 81%-91%) and partial in 7, with an overall response rate of 91%
      (95% CI, 87%-95%). At a median follow-up of 54 months (range, 3-218), 107 (67%)
      patients remained relapse-free, with a 5-year progression-free survival of 68%
      (SE: 4). Four (2.5%) patients had meningeal relapse; 119 patients were alive (113
      disease-free), with a 5-year overall survival of 75% (SE: 4). Patients managed
      with primary chemotherapy, whether followed by radiotherapy or not, had a
      significantly better outcome than patients treated with primary radiotherapy,
      whether followed by chemotherapy or not. The addition of consolidative
      radiotherapy after primary chemotherapy was not associated with improved outcome;
      doses >36 Gy and the irradiation of the whole affected bone were not associated
      with better outcome. CONCLUSION: Patients with PB-DLBCL exhibit a favorable
      prognosis when treated with primary anthracycline-based chemotherapy whether
      followed by radiotherapy or not. In patients treated with chemoradiotherapy, the
      use of larger radiation fields and doses is not associated with better outcome.
      Central nervous system dissemination is a rare event in PB-DLBCL patients.

PMID- 24567285
TI  - Development of a method for the determination of total bisphenol a at trace
      levels in human blood and urine and elucidation of factors influencing method
      accuracy and sensitivity.
AB  - This publication describes a method for the determination of total bisphenol A
      (BPA and conjugated BPA) following enzyme hydrolysis and is intended as a
      companion to our previously developed analytical method for the determination of
      free BPA (the aglycone) in human blood and urine using high-performance liquid
      chromatography-tandem mass spectrometry ( 1). That free BPA method provided a
      means to account for and/or eliminate background contamination and demonstrated
      accuracy and reproducibility in both matrices fortified with BPA or a surrogate
      analyte ((13)C BPA) at a low method quantitation limit (MQL) of 0.1-0.2 ng/mL. In
      contrast to the free BPA method results and based on stringent accuracy,
      precision and confirmation criteria set for the MQLs of the method developed for
      total BPA, the MQL achieved in blood was 1.020-2.550 and 0.510-1.020 ng/mL in
      urine. These data showed higher MQLs than the desired MQLs of 0.5 ng/mL (blood)
      and 0.2 ng/mL (urine) with increased variability between analyses which
      demonstrates the importance of generating method validation data with each
      analysis. In contrast, the MQL achieved for (13)C BPA-G (monoglucuronide as a
      surrogate analyte in blood was 0.2-0.5 and 0.2 ng/mL in urine illustrating that
      the method is capable of meeting lower MQL requirements if the contribution from
      exogenous BPA can be well controlled. This method for the determination total BPA
      in human blood and urine is intended to be used in conjunction with the free BPA
      method ( 1) to obtain accurate and complete BPA biomonitoring data to support
      human exposure assessments. 

PMID- 24567286
TI  - Methyl methacrylate levels in orthopedic surgery: comparison of two conventional
      vacuum mixing systems.
AB  - Poly-methyl methacrylate bone cements contain methyl methacrylate (MMA), which is
      known for its sensitizing and toxic properties. Therefore, in most European
      countries and in the USA, guidelines or regulations exist for occupational
      exposures. The use of vacuum mixing systems can significantly reduce airborne MMA
      concentrations during bone setting. Our goal was to test two commonly used vacuum
      mixing systems (Palamix((r)) and Optivac((r))) using Palacos((r)) R bone cement
      for their effectiveness at preventing MMA vapor release in a series of
      standardized trials in a laboratory as well as in an operating theatre. MMA was
      quantified every second over a period of 3 min using a photoionization detector
      (MiniRAE((r)) 3000) device positioned in the breathing area of the user.
      Significant differences in MMA mean vapor concentrations over 180 s were observed
      in the two experimental spaces, with the highest mean concentrations (7.61 and
      7.98 ppm for Palamix((r)) and Optivac((r)), respectively) observed in a
      laboratory with nine air changes per hour and the lowest average concentrations
      (1.06 and 1.12 ppm for Palamix((r)) and Optivac((r)), respectively) in an
      operating theatre with laminar flow ventilation and 22 air changes per hour. No
      significant differences in overall MMA concentrations were found between the two
      vacuum mixing systems in either location. Though, differences were found between
      both systems during single mixing phases. Thus, typical handling of MMA in
      orthopedic procedures must be seen as not harmful as concentrations do not reach
      the short-term exposure limit of 100 ppm. Additionally, laminar airflow seems to
      have an influence on lowering MMA concentrations in operation theatres.

PMID- 24567287
TI  - 'SWeRF-a method for estimating the relevant fine particle fraction in bulk
      materials for classification and labelling purposes' by Pensis, Luetzenkirchen,
      and Friede.

PMID- 24567289
TI  - Economic valuation of the mortality benefits of a regulation on SO2 in 20
      European cities.
AB  - BACKGROUND: Since the 1970s, legislation has led to progress in tackling several
      air pollutants. We quantify the annual monetary benefits resulting from
      reductions in mortality from the year 2000 onwards following the implementation
      of three European Commission regulations to reduce the sulphur content in liquid
      fuels for vehicles. METHODS: We first compute premature deaths attributable to
      these implementations for 20 European cities in the Aphekom project by using a
      two-stage health impact assessment method. We then justify our choice to only
      consider mortality effects as short-term effects. We rely on European studies
      when selecting the central value of a life-year estimate (? 2005 86 600) used to
      compute the monetary benefits for each of the cities. We also conduct an
      independent sensitivity analysis as well as an integrated uncertainty analysis
      that simultaneously accounts for uncertainties concerning epidemiology and
      economic valuation. RESULTS: The implementation of these regulations is estimated
      to have postponed 2212 (95% confidence interval: 772-3663) deaths per year
      attributable to reductions in sulphur dioxide for the 20 European cities, from
      the year 2000 onwards. We obtained annual mortality benefits related to the
      implementation of the European regulation on sulphur dioxide of ? 2005 191.6
      million (95% confidence interval: ? 2005 66.9-? 2005 317.2). CONCLUSION: Our
      approach is conservative in restricting to mortality effects and to short-term
      benefits only, thus only providing the lower-bound estimate. Our findings
      underline the health and monetary benefits to be obtained from implementing
      effective European policies on air pollution and ensuring compliance with them
      over time.

PMID- 24567290
TI  - Association between economic fluctuations and road mortality in OECD countries.
AB  - Using longitudinal data from 32 Organization for Economic Co-operation and
      Development (OECD) countries (1970-2010), this article investigates association
      between annual variations in road mortality and the economic fluctuations. Two
      regression models (fixed-effects and random-coefficients) were adopted for
      estimation. The cross-country data analyses suggested that road mortality is pro
      cyclical and that the cyclicality is symmetric. Based on data from 32 OECD
      countries, an increase of on average 1% in economic growth is associated with a
      1.1% increase in road mortality, and vice versa. 

PMID- 24567288
TI  - Recruiting Chinese Americans into cancer screening intervention trials:
      strategies and outcomes.
AB  - BACKGROUND: Cancer is the leading cause of death among Asian Americans. While
      Asian Americans are the fastest growing minority population in the United States,
      they are underrepresented in cancer research and report poor adherence to cancer
      screening guidelines. PURPOSE: This study utilized data from two large randomized
      intervention trials to evaluate strategies to recruit first-generation Chinese
      American immigrants from community settings and Chinese American physician
      practices. Findings will inform effective strategies for promoting Asian American
      participation in cancer control research. METHODS: Chinese Americans who were non
      adherent to annual mammography screening guidelines (Study 1 with 664 immigrant
      women > 40 years of age) and to colorectal cancer screening guidelines (Study 2
      with 455 immigrants > 50 years of age) were enrolled from the greater Washington
      DC, New York City (NYC), and Philadelphia (PA) areas. Both studies trained
      bilingual staff to enroll Chinese-speaking participants with the aid of
      linguistically appropriate fliers and brochures to obtain consent. Study 1
      adopted community approaches and worked with community organizations to enroll
      participants. Study 2 randomly selected potential participants through 24 Chinese
      American primary-care physician offices, and mailed letters from physicians to
      enroll patients, followed by telephone calls from research staff. The success of
      recruitment approaches was assessed by yield rates based on number of
      participants approached, ineligible, and consented. RESULTS: Most participants
      (70%) of Study 1 were enrolled through in-person community approaches (e.g.,
      Chinese schools, stores, health fairs, and personal networks). The final yield of
      specific venues differed widely (6% to 100%) due to various proportions of
      ineligible subjects (2%-64%) and refusals (0%-92%). The Study 2 recruitment
      approach (physician letter followed by telephone calls) had different outcomes in
      two geographic areas, partially due to differences in demographic characteristics
      in the DC and NYC/PA areas. The community approaches enrolled more recent
      immigrants and uninsured Chinese Americans than the physician and telephone call
      approach (p < .001). Enrollment cost is provided to inform future research
      studies. LIMITATIONS: Our recruitment outcomes might not be generalizable to all
      Chinese Americans or other Asian American populations because they may vary by
      study protocols (e.g., length of trials), target populations (i.e., eligibility
      criteria), and available resources. CONCLUSIONS: Use of multiple culturally
      relevant strategies (e.g., building trusting relationships through face-to-face
      enrollment, use of bilingual and bicultural staff, use of a physician letter, and
      employing linguistically appropriate materials) was crucial for successfully
      recruiting a large number of Chinese Americans in community and clinical
      settings. Our data demonstrate that substantial effort is required for
      recruitment; studies need to budget for this effort to ensure the inclusion of
      Asian Americans in health research.

PMID- 24567291
TI  - The beliefs about pros and cons of drinking and intention to change among
      hazardous and moderate alcohol users: a population-based cross-sectional study.
AB  - BACKGROUND: Fundamental to supporting hazardous alcohol users are the rationales
      for reducing alcohol intake highlighted by the users themselves. This study
      analyses the relative importance of beliefs about pros and cons of drinking in
      relation to having an intention to reduce intake among both hazardous and
      moderate alcohol users. METHODS: Intention to change was assessed in a
      representative sample of Stockholm's population (n = 4278, response rate 56.5%).
      Alcohol use was assessed using the Alcohol Use Disorders Identification Test
      measure. A decisional balance inventory was used to examine various beliefs about
      the pros and cons of drinking, which covered affect changes, social gains and
      losses, and possible adverse effects. Independent correlations were determined by
      logistic regression using a backward exclusion procedure (P > 0.05). RESULTS:
      Higher ratings of importance were generally related to intent, whether or not the
      contrast was with having no intent or already having made a reduction. This was
      especially true for hazardous users. Only two beliefs were independently
      correlated with change among hazardous users: 'Drinking could get me addicted'
      and 'Drinking makes me more relaxed/less tense' (pseudo-R2 < 0.1). Among moderate
      users, there was no uniform pattern in the relationships. CONCLUSIONS:
      Unexpectedly, hazardous users with an intent to change rated pro arguments as
      more important than those with no intent to change. Of the investigated pros and
      cons, only a few were independently related to intention to change drinking
      behaviour. These arguments provide interesting topics in consultations. Little
      support was found for any rational decision making behind the intention to reduce
      alcohol intake.

PMID- 24567292
TI  - The relation between psychosocial risk factors and cause-specific long-term
      sickness absence.
AB  - BACKGROUND: The aim was to study the impact of psychosocial risk factors on long
      term sickness absence due to mental health problems (LSA-MH) or musculoskeletal
      disorders (LSA-MSD) in 2983 Belgian middle-aged workers. METHODS: Data were
      collected from 1372 male and 1611 female workers in the Belstress III study.
      Considered psychosocial risk factors were job demands, job control, social
      support, job strain, efforts, rewards, effort-reward imbalance and bullying.
      Prospective registered sickness absence data were collected during 12 months
      follow-up; the causes for long-term sickness absence episodes of at least 15
      consecutive days were obtained by contacting the general practitioner of the
      worker. Multiple logistic regression models were used to investigate the
      relationship between the psychosocial risk factors and LSA-MH and LSA-MSD.
      RESULTS: Higher levels of rewards at baseline were independently and
      significantly associated with a lower risk for LSA-MH. Higher levels of control
      were associated with a lower risk for LSA-MSD during follow-up. Higher job
      demands and efforts were significantly related to a lower risk for LSA-MSD.
      Finally, bullying was significantly and independently related to both LSA-MH and
      LSA-MSD during the follow-up period. CONCLUSIONS: These results suggest that
      psychosocial risk factors are related to LSA-MH and LSA-MSD, of which especially
      bullying seems to be a potent stressor.

PMID- 24567293
TI  - Geographical and climatic factors and depression risk in the SUN project.
AB  - BACKGROUND: Depression incidence has been related with seasonal periodicity and
      climate. The aim of the study was to estimate the possible association between
      depression and specific meteorological factors, namely temperature, light and
      rain. METHODS: In total, 13,938 participants from the SUN (Seguimiento
      Universidad de Navarra) cohort study were included in the analysis. Subjects were
      classified according to daily mean temperature, number of daylight hours and
      amount of rain, by year, at their geographical area of residence, data supplied
      by the Spanish Agency of Meteorology. Participants were considered as incident
      cases of depression whenever they reported a physician diagnosis of depression or
      the use of antidepressant medication in any of the follow-up questionnaires. Cox
      regression models were fit to assess the relationship between climatic and
      geographical factors and the incidence of depression. RESULTS: Male subjects
      living in the south and centre areas of Spain showed a higher risk to develop
      depression compared with those living in the north area (hazard ratio = 1.6, 95%
      CI = 1.16-2.23 and hazard ratio = 1.41, 95% CI = 1.06-1.87, respectively).
      Moreover, among males, a direct association between the number of daily light
      hours and mean temperature and the risk of depression was also found. For men,
      living in rainy areas was associated with a lower risk of developing depression.
      CONCLUSION: Our results suggest that climate-depression relationship is more
      complex than previously thought, and strongly different between men and women.

PMID- 24567294
TI  - A balancing act? Work-life balance, health and well-being in European welfare
      states.
AB  - BACKGROUND: Recent analyses have shown that adverse psychosocial working
      conditions, such as job strain and effort-reward imbalance, vary by country and
      welfare state regimes. Another work-related factor with potential impact on
      health is a poor work-life balance. The aims of this study are to determine the
      association between a poor work-life balance and poor health across a variety of
      European countries and to explore the variation of work-life balance between
      European countries. METHODS: Data from the 2010 European Working Conditions
      Survey were used with 24,096 employees in 27 European countries. Work-life
      balance is measured with a question on the fit between working hours and family
      or social commitments. The WHO-5 well-being index and self-rated general health
      are used as health indicators. Logistic multilevel models were calculated to
      assess the association between work-life balance and health indicators and to
      explore the between-country variation of a poor work-life balance. RESULTS:
      Employees reporting a poor work-life balance reported more health problems (Poor
      well-being: OR = 2.06, 95% CI = 1.83-2.31; Poor self-rated health: OR = 2.00, 95%
      CI = 1.84-2.17). The associations were very similar for men and women. A
      considerable part of the between-country variation of work-life balance is
      explained by working hours, working time regulations and welfare state regimes.
      The best overall work-life balance is reported by Scandinavian men and women.
      CONCLUSION: This study provides some evidence on the public health impact of a
      poor work-life balance and that working time regulations and welfare state
      characteristics can influence the work-life balance of employees.

PMID- 24567295
TI  - Unemployment and mental health scarring during the life course.
AB  - BACKGROUND: There has been little research on the long-term relationship between
      unemployment experiences and mental health over the life course. This article
      investigates the relationship between youth unemployment as well as that of
      unemployment experiences during later periods and mental health at ages 16, 21,
      30 and 42 years. METHODS: The study makes use of the 'Northern Swedish Cohort'
      (NSC), a 27-year prospective cohort study. The cohort, investigated at ages 16,
      18, 21, 30 and 42 years, consisted of all graduates from compulsory school in an
      industrial town in Sweden. Of the original 1083 participants, 94.3% of those
      still alive were still participating at the 27-year follow up. Mental health,
      measured through a three-item index of nervous symptoms, depressive symptoms and
      sleeping problems, was analysed using a repeated measures linear mixed models
      approach using ages 16, 21, 30 and 43 years. Unemployment exposure was measured
      as exposure to at least a 6-month spell during three periods; 18-21, 21-30 and 30
      42 years. RESULTS: Youth unemployment was shown to be significantly connected
      with poorer mental health at all three target ages, 21, 30 and 42 years. Later
      singular unemployment experiences did not appear to have the same long-term
      negative effects. There was however an accumulation in poorer mental health among
      respondents with unemployment experiences during two, and even more so three, of
      the periods. CONCLUSION: There are long-term mental health scarring effects of
      exposure to youth unemployment and multiple exposure to unemployment during the
      life course.

PMID- 24567296
TI  - Carbon in airway macrophages from children with asthma.
AB  - BACKGROUND: Airway macrophage (AM) phagocytosis is impaired in severe asthma.
      Prostaglandin (PG) E2 and D2 are increased in severe asthma and suppress AM
      phagocytic function in vitro. In this study, we sought evidence for PG-mediated
      impairment of phagocytosis of inhalable carbonaceous particulate matter (PM) by
      AM in children with severe asthma compared with mild asthmatics and healthy
      controls. METHODS: AM were obtained from children with asthma and healthy
      controls using induced sputum. AM carbon area (MUm(2)) was assessed by image
      analysis. In a subgroup of asthmatics, urinary PGE2 and PGD2 metabolites were
      measured by high-performance liquid chromatography, and PM exposure at the home
      address was modelled. Phagocytosis of PM by human monocyte-derived macrophages
      and rat AM was assessed in vitro by image analysis. RESULTS: AM carbon was 51%
      lower in children with moderate-to-severe asthma (n=36) compared with mild
      asthmatics (n=12, p<0.01) and healthy controls (n=47, p<0.01). There was no
      association between modelled PM exposure and AM carbon in 33 asthmatics who had a
      urine sample, but there was an inverse association between AM carbon and urinary
      metabolites of PGE2 and D2 (n=33, rs=-0.40, p<0.05, and rs=-0.44, p<0.01). PGE2
      10(-6) M, but not PGD2 10(-6) M, suppressed phagocytosis of PM10 by human
      macrophages in vitro (p<0.05 vs control). PGE2 10(-6) M also suppressed
      phagocytosis of PM10 by rat AM in vitro (p<0.01 vs control). CONCLUSIONS:
      Phagocytosis of inhaled carbonaceous PM by AMs is impaired in severe asthma. PGE2
      may contribute to impaired AM phagocytic function in severe asthma.

PMID- 24567298
TI  - Prenatal exposure to decabrominated diphenyl ether impairs learning ability by
      altering neural stem cell viability, apoptosis, and differentiation in rat
      hippocampus.
AB  - Background:Polybrominated diphenyl ether (PBDE) levels in children and teenagers
      were higher than those of the adults and the highest levels were found in infants
      and toddlers. 2,2',3,3',4,4',5,5',6,6'-Decabrominated diphenyl ether (BDE-209)
      readily crosses the placental barrier and produces toxicity in the developing
      fetus, particularly to the developing brain.Objectives:This present study aims to
      investigate the potential effects of prenatal BDE-209 exposure on regulation of
      neurogenesis and learning function in an experimental rat model.Methods:Pregnant
      rats received BDE-209 (10, 30, or 50 mg kg-1 day-1) or vehicle (arachis oil)
      through gastric gavage from gestation day 1 to 14 (n = 10 per group). The
      embryonic hippocampal neural stem cells (NSCs) from five pregnant rats in each
      group were collected on day 14 and cultured in vitro to determine the cell
      viability, apoptosis, and differentiation of NSCs using cell counting kit 8
      assay, flow cytometry, and immunofluorescence staining, respectively. In total,
      20 male offspring on postnatal day 25 from each group were chosen to evaluate
      learning ability using a Morris water navigation task assay.Results:The data
      showed that prenatal exposure to BDE-209 decreased cell viability and
      differentiation of NSCs but promoted apoptosis in a dose-dependent manner.
      Prenatal BDE-209 exposure also impaired rat-learning acquisition in a dose
      dependent manner.Conclusions:Prenatal BDE-209 exposure impairs rat-learning
      acquisition, possibly by affecting neurogenesis in the hippocampus during
      embryonic development.

PMID- 24567297
TI  - Systemic but not topical TRAIL-expressing mesenchymal stem cells reduce tumour
      growth in malignant mesothelioma.
AB  - Malignant pleural mesothelioma is a rare but devastating cancer of the pleural
      lining with no effective treatment. The tumour is often diffusely spread
      throughout the chest cavity, making surgical resection difficult, while systemic
      chemotherapy offers limited benefit. Bone marrow-derived mesenchymal stem cells
      (MSCs) home to and incorporate into tumour stroma, making them good candidates to
      deliver anticancer therapies. Tumour necrosis factor-related apoptosis-inducing
      ligand (TRAIL) is a pro-apoptotic molecule that selectively induces apoptosis in
      cancer cells, leaving healthy cells unaffected. We hypothesised that human MSCs
      expressing TRAIL (MSCTRAIL) would home to an in vivo model of malignant pleural
      mesothelioma and reduce tumour growth. Human MSCs transduced with a lentiviral
      vector encoding TRAIL were shown in vitro to kill multiple malignant mesothelioma
      cell lines as predicted by sensitivity to recombinant TRAIL (rTRAIL). In vivo MSC
      homing was delineated using dual fluorescence and bioluminescent imaging, and we
      observed that higher levels of MSC engraftment occur after intravenous delivery
      compared with intrapleural delivery of MSCs. Finally, we show that intravenous
      delivery of MSCTRAIL results in a reduction in malignant pleural mesothelioma
      tumour growth in vivo via an increase in tumour cell apoptosis. 

PMID- 24567300
TI  - Variation in size of laryngoscope blades used in preterm newborns.

PMID- 24567299
TI  - Do adipose tissue-derived mesenchymal stem cells ameliorate Parkinson's disease
      in rat model?
AB  - Parkinson's disease (PD) is a common neurodegenerative disorder in middle-aged
      and elderly people. This study aimed to elucidate the role of mesenchymal stem
      cells (MSCs) in management of PD in ovariectomized rat model. MSCs were excised
      from adipose tissue of both the omentum and the inguinal fat pad of male rats,
      grown, and propagated in culture; then characterized morphologically; and by the
      detection of surface markers gene expression. In this study, 40 ovariectomized
      animals were classified into 5 groups; group 1 was ovariectomized control, groups
      2 to 5 were subcutaneously administered with rotenone for 14 days after 1 month
      of ovariectomy for induction of PD. Group 2 was left untreated; groups 3, 4, and
      5 were treated with Sinemet((r)), Cerebrolysin((r)), and a single dose of adipose
      tissue-derived MSCs (ADMSCs), respectively. Y-chromosome gene (sry) was assessed
      by polymerase chain reaction (PCR) in brain tissue of the female rats. Serum
      transforming growth factor beta (TGF-beta), monocyte chemoattractant protein 1
      (MCP-1), and brain-derived neurotrophic factor (BDNF) levels were assayed using
      enzyme-linked immunosorbent assay technique. Brain dopamine level was assayed
      fluorometrically, while brain tyrosine hydroxylase (TH) gene expression was
      detected by semiquantitative real-time PCR. The PD group showed significant
      increase in serum TGF-beta and MCP-1 levels associated with significant decrease
      in serum BDNF, brain dopamine, and brain TH gene expression levels. In contrast,
      all treatments produce significant decrease in serum TGF-beta and MCP-1 levels in
      concomitant with significant increase in serum BDNF, brain dopamine, and brain TH
      gene expression levels. In conclusion, the observed improvements in the studied
      biomarkers due to ADMSCs infusion might be attributed to their immunomodulatory,
      anti-inflammatory, and neurotrophic effects. 

PMID- 24567301
TI  - Smoking-related warning messages formulated as questions positively influence
      short-term smoking behaviour.
AB  - Research demonstrated that by reformulating smoking warnings into questions,
      defensive responses in smokers are reduced and smoking-related risk perception
      increases. We explored whether these positive outcomes can be generalised to
      actual behaviour. Participants saw either a movie presenting subheadings with
      smoking-related questions or statements. Afterwards, the time was measured until
      participants lit their first cigarette. Smokers who were presented with questions
      about the harms of smoking waited longer before lighting up a cigarette than
      smokers who were presented with statements. Presenting questions instead of the
      statements seems to be an effective means to prolonging smokers' abstinence. 

PMID- 24567302
TI  - How can core self-evaluations influence job burnout? The key roles of
      organizational commitment and job satisfaction.
AB  - This study aimed to explore how core self-evaluations influenced job burnout and
      mainly focused on the confirmation of the mediator roles of organizational
      commitment and job satisfaction. A total of 583 female nurses accomplished the
      Core Self-Evaluation Scale, Organizational Commitment Scale, Minnesota
      Satisfaction Questionnaire, and Maslach Burnout Inventory-General Survey. The
      results revealed that core self-evaluations, organizational commitment, job
      satisfaction, and job burnout were significantly correlated with each other.
      Structural equation modeling indicated that core self-evaluations can
      significantly influence job burnout and are completely mediated by organizational
      commitment and job satisfaction. 

PMID- 24567303
TI  - Attributing heart attack and stroke to "Old Age": Implications for subsequent
      health outcomes among older adults.
AB  - This study assessed the extent to which older adults attribute a recent heart
      attack/stroke to "old age," and examined consequences for subsequent lifestyle
      behavior and health-care service utilization. Community-dwelling adults (N = 57,
      ages 73-98 years) were interviewed about their heart attack/stroke, and an
      objective health registry provided data on health-care utilization over a 3-year
      period. Endorsement of "old age" as a cause of heart attack/stroke negatively
      predicted lifestyle behavior change, and positively predicted frequency of
      physician visits and likelihood of hospitalization over the subsequent 3 years.
      Findings suggest the importance of considering "old age" attributions in the
      context of cardiovascular health events. 

PMID- 24567304
TI  - The histone modification H3K27me3 is retained after gene duplication and
      correlates with conserved noncoding sequences in Arabidopsis.
AB  - The histone modification H3K27me3 is involved in repression of transcription and
      plays a crucial role in developmental transitions in both animals and plants. It
      is deposited by PRC2 (Polycomb repressive complex 2), a conserved protein
      complex. In Arabidopsis thaliana, H3K27me3 is found at 15% of all genes. These
      tend to encode transcription factors and other regulators important for
      development. However, it is not known how PRC2 is recruited to target loci nor
      how this set of target genes arose during Arabidopsis evolution. To resolve the
      latter, we integrated A. thaliana gene families with five independent genome-wide
      H3K27me3 data sets. Gene families were either significantly enriched or depleted
      of H3K27me3, showing a strong impact of shared ancestry to H3K27me3 distribution.
      To quantify this, we performed ancestral state reconstruction of H3K27me3 on
      phylogenetic trees of gene families. The set of H3K27me3-marked genes changed
      less than expected by chance, suggesting that H3K27me3 was retained after gene
      duplication. This retention suggests that the PRC2-recruiting signal could be
      encoded in the DNA and also conserved among certain duplicated genes. Indeed,
      H3K27me3-marked genes were overrepresented among paralogs sharing conserved
      noncoding sequences (CNSs) that are enriched with transcription factor binding
      sites. The association of upstream CNSs with H3K27me3-marked genes represents the
      first genome-wide connection between H3K27me3 and potential regulatory elements
      in plants. Thus, we propose that CNSs likely function as part of the PRC2
      recruitment in plants. 

PMID- 24567305
TI  - Serial gene losses and foreign DNA underlie size and sequence variation in the
      plastid genomes of diatoms.
AB  - Photosynthesis by diatoms accounts for roughly one-fifth of global primary
      production, but despite this, relatively little is known about their plastid
      genomes. We report the completely sequenced plastid genomes for eight
      phylogenetically diverse diatoms and show them to be variable in size, gene and
      foreign sequence content, and gene order. The genomes contain a core set of 122
      protein-coding genes, with 15 additional genes exhibiting complex patterns of 1)
      gene losses at varying phylogenetic scales, 2) functional transfers to the
      nucleus, 3) gene duplication, divergence, and differential retention of paralogs,
      and 4) acquisitions of putatively functional recombinase genes from resident
      plasmids. The newly sequenced genomes also contain several previously unreported
      genes, highlighting how poorly characterized diatom plastid genomes are overall.
      Genome size variation reflects major expansions of the inverted repeat region in
      some cases but, more commonly, large-scale expansions of intergenic regions, many
      of which contain unique open reading frames of likely foreign origin. Although
      many gene clusters are conserved across species, rearrangements appear to be
      frequent in most lineages. 

PMID- 24567307
TI  - Presenting quality data to vulnerable groups: charts, summaries or behavioral
      economic nudges?
AB  - OBJECTIVES: Despite the increased focus on health care consumers' active choice,
      not enough is known about how to best facilitate the choice process. We sought to
      assess methods of improving this process for vulnerable consumers in the United
      States by testing alternatives that emphasize insights from behavioral economics,
      or 'nudges'. METHODS: We performed a hypothetical choice experiment where
      subjects were randomized to one of five experimental conditions and asked to
      choose a health center (location where they would receive all their care). The
      conditions presented the same information about health centers in different ways,
      including graphically as a chart, via written summary and using behavioral
      economics, 'nudging' consumers toward particular choices. We hypothesized that
      these 'nudges' might help simplify the choice process. Our primary outcomes
      focused on the health center chosen and whether consumers were willing to accept
      'nudges'. RESULTS: We found that consumer choice was influenced by the method of
      presentation and the majority of consumers accepted the health center they were
      'nudged' towards. CONCLUSIONS: Consumers were accepting of choices grounded in
      insights from behavioral economics and further consideration should be given to
      their role in patient choice.

PMID- 24567306
TI  - The evolution of the GPCR signaling system in eukaryotes: modularity,
      conservation, and the transition to metazoan multicellularity.
AB  - The G-protein-coupled receptor (GPCR) signaling system is one of the main
      signaling pathways in eukaryotes. Here, we analyze the evolutionary history of
      all its components, from receptors to regulators, to gain a broad picture of its
      system-level evolution. Using eukaryotic genomes covering most lineages sampled
      to date, we find that the various components of the GPCR signaling pathway
      evolved independently, highlighting the modular nature of this system. Our data
      show that some GPCR families, G proteins, and regulators of G proteins
      diversified through lineage-specific diversifications and recurrent domain
      shuffling. Moreover, most of the gene families involved in the GPCR signaling
      system were already present in the last common ancestor of eukaryotes.
      Furthermore, we show that the unicellular ancestor of Metazoa already had most of
      the cytoplasmic components of the GPCR signaling system, including, remarkably,
      all the G protein alpha subunits, which are typical of metazoans. Thus, we show
      how the transition to multicellularity involved conservation of the signaling
      transduction machinery, as well as a burst of receptor diversification to cope
      with the new multicellular necessities. 

PMID- 24567310
TI  - High cost is the primary barrier reported by physicians who prescribe vaccines
      not included in India's Universal Immunization Program.
AB  - Haemophilus influenzae type B (Hib) vaccine, pneumococcal conjugate vaccine (PCV)
      and rotavirus (RV) vaccine are available in the private market in India, but,
      except for Hib in eight states, are not included in India's Universal
      Immunization Program (UIP). Pediatricians were surveyed about administering non
      UIP vaccines. Most give these vaccines to some of their patients (73-83%,
      depending on vaccine), but few give them to all patients (7-18%). High cost was
      the most frequently cited barrier (93-96%). Only 10-12% of respondents had
      concerns about the efficacy of PCV or RV vaccine, and concerns about Hib vaccine
      efficacy or any vaccine safety issues were rare (1-3%). Practice varied by type
      of healthcare facility, with pediatricians at government hospitals least likely
      to administer non-UIP vaccines. Support for the inclusion of all three in the UIP
      was high (83-95%). Including Hib vaccine, PCV and RV vaccine in India's UIP would
      be supported by pediatricians and help eliminate the current barrier of high cost
      of these immunizations. 

PMID- 24567308
TI  - Tempo and mode of regulatory evolution in Drosophila.
AB  - Genetic changes affecting gene expression contribute to phenotypic divergence;
      thus, understanding how regulatory networks controlling gene expression change
      over time is critical for understanding evolution. Prior studies of expression
      differences within and between species have identified properties of regulatory
      divergence, but technical and biological differences among these studies make it
      difficult to assess the generality of these properties or to understand how
      regulatory changes accumulate with divergence time. Here, we address these issues
      by comparing gene expression among strains and species of Drosophila with a range
      of divergence times and use F1 hybrids to examine inheritance patterns and
      disentangle cis- and trans-regulatory changes. We find that the fixation of
      compensatory changes has caused the regulation of gene expression to diverge more
      rapidly than gene expression itself. Specifically, we observed that the
      proportion of genes with evidence of cis-regulatory divergence has increased more
      rapidly with divergence time than the proportion of genes with evidence of
      expression differences. Surprisingly, the amount of expression divergence
      explained by cis-regulatory changes did not increase steadily with divergence
      time, as was previously proposed. Rather, one species (Drosophila sechellia)
      showed an excess of cis-regulatory divergence that we argue most likely resulted
      from positive selection in this lineage. Taken together, this work reveals not
      only the rate at which gene expression evolves, but also the molecular and
      evolutionary mechanisms responsible for this evolution. 

PMID- 24567309
TI  - Effect of multivitamin supplementation on the neurodevelopment of HIV-exposed
      Tanzanian infants: a randomized, double-blind, placebo-controlled clinical trial.
AB  - BACKGROUND: Micronutrient deficiencies and in utero exposure to HIV may impair
      infant neurodevelopment. OBJECTIVE: To evaluate the effect of daily multivitamin
      supplementation on the cognitive, language and motor development of HIV-exposed
      Tanzanian infants. METHODS: A total of 2387 infants were randomized to receive
      daily oral supplementation of multivitamins (B-complex, C and E) or placebo from
      age 6 weeks for 24 months. The cognitive, language and motor scales of the Bayley
      Scales of Infant and Toddler Development, third edition, were administered to a
      subset of 206 infants at age 15 months. RESULTS: Multivitamin supplementation did
      not improve measures of cognitive development, expressive or receptive language
      or gross motor capabilities. There was a trend toward improved fine motor skills
      among infants randomized to the multivitamin group (difference in mean score =
      0.38; 95% CI = -0.01, 0.78, p = 0.06). CONCLUSION: Daily provision of
      multivitamins to HIV-exposed infants does not substantially improve developmental
      outcomes at age 15 months.

PMID- 24567311
TI  - Successful treatment of an infant infected with refractory C. parapsilosis with
      caspofungin.
AB  - Neonatal Candida infections are the leading cause of invasive fungal infections
      that might cause severe morbidity or mortality in a large majority of those
      affected. Although Candida albicans has been the most common species, Candida
      parapsilosis is increasingly being recognized as an important cause of invasive
      candidiasis in neonates. Among the Candida species, C. parapsilosis has been
      commonly isolated and shown to be less susceptible in vitro to echinocandins than
      other Candida species. We report an infant who had refractory C. parapsilosis
      septicemia cured with caspofungin. 

PMID- 24567312
TI  - Eau de Dalibour vs. alcohol for umbilical cord care.
AB  - This study was conducted to compare the effects of Eau de Dalibour and ethanol on
      preventing omphalitis and also on umbilical cord separation time in neonates. In
      this clinical trial, 178 randomly selected, healthy term neonates were
      investigated. To disinfect the umbilical cords, Eau de Dalibour was used for 84
      infants (case group) and ethanol for 94 infants (control group). No cases of
      omphalitis were observed in either group. Umbilical cord separation time was
      significantly shorter in the Eau de Dalibour group than in the ethanol group:
      4.04 +/- 1.61 days vs. 6.3 +/- 1.82 days, p = 0.001. This study revealed that
      although Eau de Dalibour and ethanol were equally effective in preventing the
      incidence of omphalitis in neonates, Eau de Dalibour induced the separation of
      umbilical cord significantly quicker in the infants. Thus, Eau de Dalibour could
      be used as a suitable replacement for ethanol in neonates' umbilical cord care. 

PMID- 24567313
TI  - Revisiting the paradox of well-being: the importance of national context.
AB  - OBJECTIVES: Despite age-related changes or declines in circumstances, health or
      income, many older people are able to maintain subjective well-being (SWB) in
      later life. This is known as the paradox of well-being. To date, much research
      has focused on either individual- (e.g., age, health, and income) or country
      level (e.g., national wealth, inequality) differences in SWB. The present
      research investigates how these levels combine, and whether the paradox of well
      being persists across different economic contexts. METHOD: This research uses the
      2008-2009 European Social Survey to test the multilevel hypothesis that economic
      circumstances, reflected by a country's Gross Domestic Product (GDP), affect the
      paradox of well-being, that is, the relationship between age and SWB. Analyses
      also account for other relevant psychological, individual, and country
      differences. Possible avenues by which GDP affects SWB are also explored.
      RESULTS: The multilevel analysis revealed that GDP disproportionally affects the
      SWB of older people relative to younger people, and that the paradox of well
      being is only observed in countries with higher GDP. DISCUSSION: The findings
      clarify the relationship between age and SWB by demonstrating that the paradox of
      well-being is conditional on the economic context. Implications for individual-
      and country-level strategies for successful aging are discussed.

PMID- 24567314
TI  - Development of a composite model derived from cardiopulmonary exercise tests to
      predict mortality risk in patients with mild-to-moderate heart failure.
AB  - OBJECTIVE: Cardiopulmonary exercise testing (CPET) is used to predict outcome in
      patients with mild-to-moderate heart failure (HF). Single CPET-derived variables
      are often used, but we wanted to see if a composite score achieved better
      predictive power. METHODS: Retrospective analysis of patient records at the
      department of cardiology, Castle Hill Hospital, Kingston-upon-Hull. 387 patients
      (median (25th-75th percentile)) (age 65 (56-72) years; 79% men; LVEF 34 (31-37)
      %) were included. Patients underwent a symptom-limited, maximal CPET on a
      treadmill. During a median follow-up of 8.6+/-2.1 years in survivors, 107
      patients died. Survival models were built and validated using a hybrid approach
      between the bootstrap and Cox regression. Nine CPET-derived variables were
      included. Z-score defined each variable's predictive strength. Model coefficients
      were converted to a risk score. RESULTS: Four CPET-related variables were
      independent predictors of all-cause mortality in the survival model: the presence
      of exertional oscillatory ventilation (EOV), increasing slope of the relation
      between ventilation and carbon dioxide production (VE/VCO2 slope), decreasing
      oxygen uptake efficiency slope (OUES), and an increase in the lowest ventilatory
      equivalent for carbon dioxide (VEqCO2 nadir). Individual predictors of mortality
      ranged from 0.60 to 0.71 using Harrell's C-statistic, but the optimal combination
      of EOV+VE/VCO2 slope+OUES+VEqCO2 nadir reached 0.75. The Hull CPET risk score had
      a significantly higher area under the curve (0.78) when compared to the HF
      Survival Score (AUC=0.70; p<0.001). CONCLUSIONS: A composite risk score using
      variables from CPET out-performs the traditional single variable approach in
      predicting outcome in patients with mild-to-moderate HF.

PMID- 24567315
TI  - Comparative study on waterborne parasites between Malaysia and Thailand: A new
      insight.
AB  - This study investigated the distribution of parasites as main contaminants in
      water environments of peninsular Malaysia (October 2011-December 2011) and the
      southeastern coast of Thailand (June 2012). Sixty-four water samples, 33 from
      Malaysia and 31 from Thailand, of various water types were examined according to
      U.S. Environmental Protection Agency guidelines. Drinking or household water
      types from both countries were free from parasitic contamination. The
      recreational/environmental (except a swimming pool in Malaysia) and effluent
      water types from these two countries were contaminated with waterborne parasites:
      Giardia (0.04-4 cysts/L), Cryptosporidium (0.06-2.33 oocysts/L), hookworm (6.67
      350 ova/L), Ascaris (0.33-33.33 ova/L), and Schistosoma (9.25-13.33 ova/L). The
      most contaminated sites were recreational lake garden 3 in Malaysia and river 2
      in Thailand. Higher concentrations of Giardia, Cryptosporidium, and hookworm were
      found in samples from Malaysia than in samples from Thailand. The presence of
      Giardia cysts showed a significant association with the presence of
      Cryptosporidium oocysts (P < 0.005).

PMID- 24567316
TI  - Clinical and immunological outcome in cutaneous leishmaniasis patients treated
      with pentoxifylline.
AB  - Pentoxifylline is a tumor necrosis factor-alpha (TNF-alpha) inhibitor that also
      attenuates the immune response and decreases tissue inflammation. The association
      of pentoxifylline with antimony improves the cure rate of mucosal and cutaneous
      leishmaniasis. In this randomized and double blind pilot trial, cure rate was
      higher, although not significant, in patients who received antimony plus
      pentoxifylline than in those patients receiving antimony plus placebo. A
      significant decrease in TNF-alpha and interferon-gamma (IFN-gamma) levels during
      therapy was more pronounced in the antimony plus pentoxifylline group, whereas
      CCL-3 (Chemokine [C-C motif] ligand 3) decreased similarly in both groups. The
      increased levels of CXCL-9 (Chemokine [C-X-C motif] ligand 9) during therapy were
      lower in the antimony plus pentoxifylline group. Therapy with pentoxifylline
      modifies cytokines and chemokines production, which may be associated with
      therapeutic outcome.

PMID- 24567317
TI  - Correlation between presence of Trypanosoma cruzi DNA in heart tissue of baboons
      and cynomolgus monkeys, and lymphocytic myocarditis.
AB  - Trypanosoma cruzi, the causative agent of Chagas' disease, preferentially infects
      cardiac and digestive tissues. Baboons living in Texas (Papio hamadryas) and
      cynomolgus monkeys (Macaca fascicularis) have been reported to be infected
      naturally with T. cruzi. In this study, we retrospectively reviewed cases of
      animals that were diagnosed with lymphocytic myocarditis and used a polymerase
      chain reaction (PCR)-based method (S36/S35 primer set) to amplify T. cruzi DNA
      from archived frozen and formalin-fixed paraffin-embedded (FFPE) cardiac tissues.
      We show that the PCR method is applicable in archived frozen and FFPE tissues and
      the sensitivity is in the femtogram range. A positive correlation between PCR
      positivity and lymphocytic myocarditis in both baboons and cynomolgus monkeys is
      shown. We also show epicarditis as a common finding in animals infected with T.
      cruzi.

PMID- 24567318
TI  - Impact of rainfall on diarrheal disease risk associated with unimproved water and
      sanitation.
AB  - Diarrheal disease remains a leading cause of morbidity in areas with limited
      access to safe water and sanitation. As water and sanitation interventions
      continue to be implemented, it will be important to understand the ecological
      context in which they can prevent diarrhea. We conducted six serial case control
      studies in Ecuador to estimate the risk of diarrhea from unimproved water and
      sanitation and the potential for effect modification by rainfall. Unimproved
      water source and unimproved sanitation increased the adjusted odds of diarrhea
      (odds ratio [OR] = 3.6, 95% confidence interval [95% CI] = 1.7-7.8 and OR = 1.7,
      95% CI = 1.2-2.5, respectively). The OR associated with an unimproved water
      source was highest after maximum rainfall (OR = 6.8, 95% CI = 1.9-24.5), whereas
      the OR associated with unimproved sanitation was highest after minimal rainfall
      (OR = 2.9, 95% CI = 1.3-6.6). Our finding that use of safe water sources and
      improved sanitation facilities are most protective under opposing rainfall
      conditions highlights the need for integrated interventions to reduce the burden
      of diarrheal disease.

PMID- 24567319
TI  - Vector competence of Culex neavei and Culex quinquefasciatus (Diptera: Culicidae)
      from Senegal for lineages 1, 2, Koutango and a putative new lineage of West Nile
      virus.
AB  - West Nile virus (WN virus) is one of the most widespread arbovirus and exhibits a
      great genetic diversity with 8 lineages, at least 4 (1, 2, Koutango, and putative
      new) are present in Africa. In West Africa, Culex neavei and Culex
      quinquefasciatus are considered as potential vectors for WN virus transmission in
      sylvatic or urban context. We analyzed the vector competence of these Culex
      species from Senegal for African lineages and envelope proteins sequences of
      viral strains used. We showed that lineage 1 is transmitted by both Culex
      mosquitoes, whereas the putative new lineage 8 is transmitted only by Cx. neavei.
      Our findings suggest that genetic variability can affect vector competence and
      depend on mosquito. However, when considering the infective life rate, the
      mosquito population seems to be inefficient for WN virus transmission in the
      field and could explain the low impact of WN virus in Africa.

PMID- 24567320
TI  - Epidemiology of Staphylococcus aureus harboring the mecA or Panton-Valentine
      leukocidin genes in hospitals in Java and Bali, Indonesia.
AB  - Data of Staphylococcus aureus carriage in Indonesian hospitals are scarce.
      Therefore, the epidemiology of S. aureus among surgery patients in three academic
      hospitals in Indonesia was studied. In total, 366 of 1,502 (24.4%) patients
      carried S. aureus. The methicillin-resistant S. aureus (MRSA) carriage rate was
      4.3%, whereas 1.5% of the patients carried Panton-Valentine leukocidin (PVL)
      positive methicillin-sensitive S. aureus (MSSA). Semarang and Malang city (odds
      ratio [OR] 9.4 and OR 9.0), being male (OR 2.4), hospitalization for more than 5
      days (OR 11.708), and antibiotic therapy during hospitalization (OR 2.6) were
      independent determinants for MRSA carriage, whereas prior hospitalization (OR
      2.5) was the only one risk factor for PVL-positive MSSA carriage. Typing of MRSA
      strains by Raman spectroscopy showed three large clusters assigned type 21, 24,
      and 38, all corresponding to ST239-MRSA-SCCmec type III. In conclusion, MRSA and
      PVL-positive MSSA are present among patients in surgical wards in Indonesian
      academic hospitals.

PMID- 24567321
TI  - Crystal structure and molecular imaging of the Nav channel beta3 subunit
      indicates a trimeric assembly.
AB  - The vertebrate sodium (Nav) channel is composed of an ion-conducting alpha
      subunit and associated beta subunits. Here, we report the crystal structure of
      the human beta3 subunit immunoglobulin (Ig) domain, a functionally important
      component of Nav channels in neurons and cardiomyocytes. Surprisingly, we found
      that the beta3 subunit Ig domain assembles as a trimer in the crystal asymmetric
      unit. Analytical ultracentrifugation confirmed the presence of Ig domain
      monomers, dimers, and trimers in free solution, and atomic force microscopy
      imaging also detected full-length beta3 subunit monomers, dimers, and trimers.
      Mutation of a cysteine residue critical for maintaining the trimer interface
      destabilized both dimers and trimers. Using fluorescence photoactivated
      localization microscopy, we detected full-length beta3 subunit trimers on the
      plasma membrane of transfected HEK293 cells. We further show that beta3 subunits
      can bind to more than one site on the Nav 1.5 alpha subunit and induce the
      formation of alpha subunit oligomers, including trimers. Our results suggest a
      new and unexpected role for the beta3 subunits in Nav channel cross-linking and
      provide new structural insights into some pathological Nav channel mutations. 

PMID- 24567322
TI  - DJ-1 is a copper chaperone acting on SOD1 activation.
AB  - Lack of oxidative stress control is a common and often prime feature observed in
      many neurodegenerative diseases. Both DJ-1 and SOD1, proteins involved in
      familial Parkinson disease and amyotrophic lateral sclerosis, respectively, play
      a protective role against oxidative stress. Impaired activity and modified
      expression of both proteins have been observed in different neurodegenerative
      diseases. A potential cooperative action of DJ-1 and SOD1 in the same oxidative
      stress response pathway may be suggested based on a copper-mediated interaction
      between the two proteins reported here. To investigate the mechanisms underlying
      the antioxidative function of DJ-1 in relation to SOD1 activity, we investigated
      the ability of DJ-1 to bind copper ions. We structurally characterized a novel
      copper binding site involving Cys-106, and we investigated, using different
      techniques, the kinetics of DJ-1 binding to copper ions. The copper transfer
      between the two proteins was also examined using both fluorescence spectroscopy
      and specific biochemical assays for SOD1 activity. The structural and functional
      analysis of the novel DJ-1 copper binding site led us to identify a putative role
      for DJ-1 as a copper chaperone. Alteration of the coordination geometry of the
      copper ion in DJ-1 may be correlated to the physiological role of the protein, to
      a potential failure in metal transfer to SOD1, and to successive implications in
      neurodegenerative etiopathogenesis. 

PMID- 24567323
TI  - Regulation of Ku-DNA association by Yku70 C-terminal tail and SUMO modification.
AB  - The Ku70-Ku80 ring complex encloses DNA ends to facilitate telomere maintenance
      and DNA break repair. Many studies focus on the ring-forming regions of subunits
      Ku70 and Ku80. Less is known about the Ku70 C-terminal tail, which lies outside
      the ring. Our results suggest that this region is responsible for dynamic
      sumoylation of Yku70 upon DNA association in budding yeast. Mutating a cluster of
      five lysines in this region largely eliminates Yku70 sumoylation. Chromatin
      immunoprecipitation analyses show that yku70 mutants with these lysines replaced
      by arginines exhibit reduced Ku-DNA association at both telomeres and internal
      DNA breaks. Consistent with this physical evidence, Yku70 sumoylation deficiency
      is associated with impaired ability to block DNA end resection and suppression of
      multiple defects caused by inefficient resection. Correlating with these, yku70
      mutants with reduced sumoylation levels exhibit shorter telomeres, increased G
      overhang levels, and altered levels of non-homologous end joining. We also show
      that diminution of sumoylation does not affect Yku70 protein levels or its
      interactions with protein and RNA partners. These results suggest a model whereby
      Yku70 sumoylation upon DNA association strengthens Ku-DNA interaction to promote
      multiple functions of Ku. 

PMID- 24567325
TI  - Sequential delivery of synaptic GluA1- and GluA4-containing AMPA receptors
      (AMPARs) by SAP97 anchored protein complexes in classical conditioning.
AB  - Multiple signaling pathways are involved in AMPAR trafficking to synapses during
      synaptic plasticity and learning. The mechanisms for how these pathways are
      coordinated in parallel but maintain their functional specificity involves
      subcellular compartmentalization of kinase function by scaffolding proteins, but
      how this is accomplished is not well understood. Here, we focused on
      characterizing the molecular machinery that functions in the sequential synaptic
      delivery of GluA1- and GluA4-containing AMPARs using an in vitro model of
      eyeblink classical conditioning. We show that conditioning induces the
      interaction of selective protein complexes with the key structural protein SAP97,
      which tightly regulates the synaptic delivery of GluA1 and GluA4 AMPAR subunits.
      The results demonstrate that in the early stages of conditioning the initial
      activation of PKA stimulates the formation of a SAP97-AKAP/PKA-GluA1 protein
      complex leading to synaptic delivery of GluA1-containing AMPARs through a SAP97
      PSD95 interaction. This is followed shortly thereafter by generation of a SAP97
      KSR1/PKC-GluA4 complex for GluA4 AMPAR subunit delivery again through a SAP97
      PSD95 interaction. These data suggest that SAP97 forms the molecular backbone of
      a protein scaffold critical for delivery of AMPARs to the PSD during
      conditioning. Together, the findings reveal a cooperative interaction of multiple
      scaffolding proteins for appropriately timed delivery of subunit-specific AMPARs
      to synapses and support a sequential two-stage model of AMPAR synaptic delivery
      during classical conditioning. 

PMID- 24567324
TI  - Structure-function elucidation of a new alpha-conotoxin, Lo1a, from Conus
      longurionis.
AB  - alpha-Conotoxins are peptide toxins found in the venom of marine cone snails and
      potent antagonists of various subtypes of nicotinic acetylcholine receptors
      (nAChRs). nAChRs are cholinergic receptors forming ligand-gated ion channels in
      the plasma membranes of certain neurons and the neuromuscular junction. Because
      nAChRs have an important role in regulating transmitter release, cell
      excitability, and neuronal integration, nAChR dysfunctions have been implicated
      in a variety of severe pathologies such as epilepsy, myasthenic syndromes,
      schizophrenia, Parkinson disease, and Alzheimer disease. To expand the knowledge
      concerning cone snail toxins, we examined the venom of Conus longurionis. We
      isolated an 18-amino acid peptide named alpha-conotoxin Lo1a, which is active on
      nAChRs. To the best of our knowledge, this is the first characterization of a
      conotoxin from this species. The peptide was characterized by
      electrophysiological screening against several types of cloned nAChRs expressed
      in Xenopus laevis oocytes. The three-dimensional solution structure of the alpha
      conotoxin Lo1a was determined by NMR spectroscopy. Lo1a, a member of the alpha4/7
      family, blocks the response to acetylcholine in oocytes expressing alpha7 nAChRs
      with an IC50 of 3.24 +/- 0.7 MUM. Furthermore, Lo1a shows a high selectivity for
      neuronal versus muscle subtype nAChRs. Because Lo1a has an unusual C terminus, we
      designed two mutants, Lo1a-DeltaD and Lo1a-RRR, to investigate the influence of
      the C-terminal residue. Lo1a-DeltaD has a C-terminal Asp deletion, whereas in
      Lo1a-RRR, a triple-Arg tail replaces the Asp. They blocked the neuronal nAChR
      alpha7 with a lower IC50 value, but remarkably, both adopted affinity for the
      muscle subtype alpha1beta1deltaepsilon.

PMID- 24567327
TI  - Molecular basis for preventing alpha-synuclein aggregation by a molecular
      tweezer.
AB  - Recent work on alpha-synuclein has shown that aggregation is controlled
      kinetically by the rate of reconfiguration of the unstructured chain, such that
      the faster the reconfiguration, the slower the aggregation. In this work we
      investigate this relationship by examining alpha-synuclein in the presence of a
      small molecular tweezer, CLR01, which binds selectively to Lys side chains. We
      find strong binding to multiple Lys within the chain as measured by fluorescence
      and mass-spectrometry and a linear increase in the reconfiguration rate with
      concentration of the inhibitor. Top-down mass-spectrometric analysis shows that
      the main binding of CLR01 to alpha-synuclein occurs at the N-terminal Lys-10/Lys
      12. Photo-induced cross-linking of unmodified proteins (PICUP) analysis shows
      that under the conditions used for the fluorescence analysis, alpha-synuclein is
      predominantly monomeric. The results can be successfully modeled using a kinetic
      scheme in which two aggregation-prone monomers can form an encounter complex that
      leads to further oligomerization but can also dissociate back to monomers if the
      reconfiguration rate is sufficiently high. Taken together, the data provide
      important insights into the preferred binding site of CLR01 on alpha-synuclein
      and the mechanism by which the molecular tweezer prevents self-assembly into
      neurotoxic aggregates by alpha-synuclein and presumably other amyloidogenic
      proteins. 

PMID- 24567326
TI  - Ca2+-binding motif of betagamma-crystallins.
AB  - betagamma-Crystallin-type double clamp (N/D)(N/D)XX(S/T)S motif is an established
      but sparsely investigated motif for Ca(2+) binding. A betagamma-crystallin domain
      is formed of two Greek key motifs, accommodating two Ca(2+)-binding sites.
      betagamma-Crystallins make a separate class of Ca(2+)-binding proteins (CaBP),
      apparently a major group of CaBP in bacteria. Paralleling the diversity in
      betagamma-crystallin domains, these motifs also show great diversity, both in
      structure and in function. Although the expression of some of them has been
      associated with stress, virulence, and adhesion, the functional implications of
      Ca(2+) binding to betagamma-crystallins in mediating biological processes are yet
      to be elucidated. 

PMID- 24567328
TI  - Activated platelets interfere with recruitment of mesenchymal stem cells to
      apoptotic cardiac cells via high mobility group box 1/Toll-like receptor 4
      mediated down-regulation of hepatocyte growth factor receptor MET.
AB  - Recruitment of mesenchymal stem cells (MSC) following cardiac injury, such as
      myocardial infarction, plays a critical role in tissue repair and may contribute
      to myocardial recovery. However, the mechanisms that regulate migration of MSC to
      the site of tissue damage remain elusive. Here, we demonstrate in vitro that
      activated platelets substantially inhibit recruitment of MSC toward apoptotic
      cardiac myocytes and fibroblasts. The alarmin high mobility group box 1 (HMGB1)
      was released by platelets upon activation and mediated inhibition of the cell
      death-dependent migratory response through Toll-like receptor (TLR)-4 expressed
      on the MSC. Migration of MSC to apoptotic cardiac myocytes and fibroblasts was
      driven by hepatocyte growth factor (HGF), and platelet activation was followed by
      HMGB1/TLR-4-dependent down-regulation of HGF receptor MET on MSC, thereby
      impairing HGF-driven MSC recruitment. We identify a novel mechanism by which
      platelets, upon activation, interfere with MSC recruitment to apoptotic cardiac
      cells, a process that may be of particular relevance for myocardial repair and
      regeneration. 

PMID- 24567329
TI  - Vfa1 binds to the N-terminal microtubule-interacting and trafficking (MIT) domain
      of Vps4 and stimulates its ATPase activity.
AB  - The endosomal sorting complexes required for transport (ESCRT) are responsible
      for multivesicular body biogenesis, membrane abscission during cytokinesis, and
      retroviral budding. They function as transiently assembled molecular complexes on
      the membrane, and their disassembly requires the action of the AAA-ATPase Vps4.
      Vps4 is regulated by a multitude of ESCRT and ESCRT-related proteins. Binding of
      these proteins to Vps4 is often mediated via the microtubule-interacting and
      trafficking (MIT) domain of Vps4. Recently, a new Vps4-binding protein Vfa1 was
      identified in a yeast genetic screen, where overexpression of Vfa1 caused defects
      in vacuolar morphology. However, the function of Vfa1 and its role in vacuolar
      biology were largely unknown. Here, we provide the first detailed biochemical and
      biophysical study of Vps4-Vfa1 interaction. The MIT domain of Vps4 binds to the C
      terminal 17 residues of Vfa1. This interaction is of high affinity and greatly
      stimulates the ATPase activity of Vps4. The crystal structure of the Vps4-Vfa1
      complex shows that Vfa1 adopts a canonical MIT-interacting motif 2 structure that
      has been observed previously in other Vps4-ESCRT interactions. These findings
      suggest that Vfa1 is a novel positive regulator of Vps4 function. 

PMID- 24567330
TI  - No amelioration of uromodulin maturation and trafficking defect by sodium 4
      phenylbutyrate in vivo: studies in mouse models of uromodulin-associated kidney
      disease.
AB  - Uromodulin (UMOD)-associated kidney disease (UAKD) belongs to the hereditary
      progressive ER storage diseases caused by maturation defects of mutant UMOD
      protein. Current treatments of UAKD patients are symptomatic and cannot prevent
      disease progression. Two in vitro studies reported a positive effect of the
      chemical chaperone sodium 4-phenylbutyrate (4-PBA) on mutant UMOD maturation.
      Thus, 4-PBA was suggested as a potential treatment for UAKD. This study evaluated
      the effects of 4-PBA in two mouse models of UAKD. In contrast to previous in
      vitro studies, treatment with 4-PBA did not increase HSP70 expression or improve
      maturation and trafficking of mutant UMOD in vivo. Kidney function of UAKD mice
      was actually deteriorated by 4-PBA treatment. In transfected tubular epithelial
      cells, 4-PBA did not improve maturation but increased the expression level of
      both mutant and wild-type UMOD protein. Activation of NF-kappaB pathway in thick
      ascending limb of Henle's loop cells of UAKD mice was detected by increased
      abundance of RelB and phospho-IkappaB kinase alpha/beta, an indirect activator of
      NF-kappaB. Furthermore, the abundance of NF-kappaB1 p105/p50, NF-kappaB2
      p100/p52, and TRAF2 was increased in UAKD. NF-kappaB activation was identified as
      a novel disease mechanism of UAKD and might be a target for therapeutic
      intervention. 

PMID- 24567331
TI  - Coordinated nuclear and synaptic shuttling of afadin promotes spine plasticity
      and histone modifications.
AB  - The ability of a neuron to transduce extracellular signals into long lasting
      changes in neuronal morphology is central to its normal function. Increasing
      evidence shows that coordinated regulation of synaptic and nuclear signaling in
      response to NMDA receptor activation is crucial for long term memory, synaptic
      tagging, and epigenetic signaling. Although mechanisms have been proposed for
      synapse-to-nuclear communication, it is unclear how signaling is coordinated at
      both subcompartments. Here, we show that activation of NMDA receptors induces the
      bi-directional and concomitant shuttling of the scaffold protein afadin from the
      cytosol to the nucleus and synapses. Activity-dependent afadin nuclear
      translocation peaked 2 h post-stimulation, was independent of protein synthesis,
      and occurred concurrently with dendritic spine remodeling. Moreover, activity
      dependent afadin nuclear translocation coincides with phosphorylation of histone
      H3 at serine 10 (H3S10p), a marker of epigenetic modification. Critically,
      blocking afadin nuclear accumulation attenuated activity-dependent dendritic
      spine remodeling and H3 phosphorylation. Collectively, these data support a novel
      model of neuronal nuclear signaling whereby dual-residency proteins undergo
      activity-dependent bi-directional shuttling from the cytosol to synapses and the
      nucleus, coordinately regulating dendritic spine remodeling and histone
      modifications. 

PMID- 24567332
TI  - The assembly and intermolecular properties of the Hsp70-Tomm34-Hsp90 molecular
      chaperone complex.
AB  - Maintenance of protein homeostasis by molecular chaperones Hsp70 and Hsp90
      requires their spatial and functional coordination. The cooperation of Hsp70 and
      Hsp90 is influenced by their interaction with the network of co-chaperone
      proteins, some of which contain tetratricopeptide repeat (TPR) domains. Critical
      to these interactions are TPR domains that target co-chaperone binding to the
      EEVD-COOH motif that terminates Hsp70/Hsp90. Recently, the two-TPR domain
      containing protein, Tomm34, was reported to bind both Hsp70 and Hsp90. Here we
      characterize the structural basis of Tomm34-Hsp70/Hsp90 interactions. Using
      multiple methods, including pull-down assays, fluorescence polarization,
      hydrogen/deuterium exchange, and site-directed mutagenesis, we defined the
      binding activities and specificities of Tomm34 TPR domains toward Hsp70 and
      Hsp90. We found that Tomm34 TPR1 domain specifically binds Hsp70. This
      interaction is partly mediated by a non-canonical TPR1 two-carboxylate clamp and
      is strengthened by so far unidentified additional intermolecular contacts. The
      two-carboxylate clamp of the isolated TPR2 domain has affinity for both
      chaperones, but as part of the full-length Tomm34 protein, the TPR2 domain binds
      specifically Hsp90. These binding properties of Tomm34 TPR domains thus enable
      simultaneous binding of Hsp70 and Hsp90. Importantly, we provide evidence for the
      existence of an Hsp70-Tomm34-Hsp90 tripartite complex. In addition, we defined
      the basic conformational demands of the Tomm34-Hsp90 interaction. These results
      suggest that Tomm34 represents a novel scaffolding co-chaperone of Hsp70 and
      Hsp90, which may facilitate Hsp70/Hsp90 cooperation during protein folding. 

PMID- 24567333
TI  - Interleukin 1/Toll-like receptor-induced autophosphorylation activates
      interleukin 1 receptor-associated kinase 4 and controls cytokine induction in a
      cell type-specific manner.
AB  - IRAK4 is a central kinase in innate immunity, but the role of its kinase activity
      is controversial. The mechanism of activation for IRAK4 is currently unknown, and
      little is known about the role of IRAK4 kinase in cytokine production,
      particularly in different human cell types. We show IRAK4 autophosphorylation
      occurs by an intermolecular reaction and that autophosphorylation is required for
      full catalytic activity of the kinase. Phosphorylation of any two of the residues
      Thr-342, Thr-345, and Ser-346 is required for full activity, and the death domain
      regulates the activation of IRAK4. Using antibodies against activated IRAK4, we
      demonstrate that IRAK4 becomes phosphorylated in human cells following
      stimulation by IL-1R and Toll-like receptor agonists, which can be blocked
      pharmacologically by a dual inhibitor of IRAK4 and IRAK1. Interestingly, in
      dermal fibroblasts, although complete inhibition of IRAK4 kinase activity does
      not inhibit IL-1-induced IL-6 production, NF-kappaB, or MAPK activation, there is
      complete ablation of these processes in IRAK4-deficient cells. In contrast, the
      inhibition of IRAK kinase activity in primary human monocytes reduces R848
      induced IL-6 production with minimal effect on NF-kappaB or MAPK activation.
      Taken together, these studies define the mechanism of IRAK4 activation and
      highlight the differential role of IRAK4 kinase activity in different human cell
      types as well as the distinct roles IRAK4 scaffolding and kinase functions play. 

PMID- 24567334
TI  - Galectin-3 regulates desmoglein-2 and intestinal epithelial intercellular
      adhesion.
AB  - The desmosomal cadherins, desmogleins, and desmocollins mediate strong
      intercellular adhesion. Human intestinal epithelial cells express the desmoglein
      2 isoform. A proteomic screen for Dsg2-associated proteins in intestinal
      epithelial cells identified a lectin referred to as galectin-3 (Gal3). Gal3 bound
      to N-linked beta-galactosides in Dsg2 extracellular domain and co-sedimented with
      caveolin-1 in lipid rafts. Down-regulation of Gal3 protein or incubation with
      lactose, a galactose-containing disaccharide that competitively inhibits galectin
      binding to Dsg2, decreased intercellular adhesion in intestinal epithelial cells.
      In the absence of functional Gal3, Dsg2 protein was internalized from the plasma
      membrane and degraded in the proteasome. These results report a novel role of
      Gal3 in stabilizing a desmosomal cadherin and intercellular adhesion in
      intestinal epithelial cells. 

PMID- 24567335
TI  - Disulfide linkage and structure of highly stable yeast-derived virus-like
      particles of murine polyomavirus.
AB  - VP1 is the major coat protein of murine polyomavirus and forms virus-like
      particles (VLPs) in vitro. VLPs consist of 72 pentameric VP1 subunits held
      together by a terminal clamp structure that is further stabilized by disulfide
      bonds and chelation of calcium ions. Yeast-derived VLPs (yVLPs) assemble
      intracellularly in vivo during recombinant protein production. These in vivo
      assembled yVLPs differ in several properties from VLPs assembled in vitro from
      bacterially produced pentamers. We found several intermolecular disulfide
      linkages in yVLPs involving 5 of the 6 cysteines of VP1 (Cys(115)-Cys(20),
      Cys(12)-Cys(20), Cys(16)-Cys(16), Cys(12)/ Cys(16)-Cys(115), and Cys(274)
      Cys(274)), indicating a highly coordinated disulfide network within the in vivo
      assembled particles involving the N-terminal region of VP1. Cryoelectron
      microscopy revealed structured termini not resolved in the published crystal
      structure of the bacterially expressed VLP that appear to clamp the pentameric
      subunits together. These structural features are probably the reason for the
      observed higher stability of in vivo assembled yVLPs compared with in vitro
      assembled bacterially expressed VLPs as monitored by increased thermal stability,
      higher resistance to trypsin cleavage, and a higher activation enthalpy of the
      disassembly reaction. This high stability is decreased following disassembly of
      yVLPs and subsequent in vitro reassembly, suggesting a role for cellular
      components in optimal assembly. 

PMID- 24567336
TI  - The essential role of p53-up-regulated modulator of apoptosis (Puma) and its
      regulation by FoxO3a transcription factor in beta-amyloid-induced neuron death.
AB  - Neurodegeneration underlies the pathology of Alzheimer disease (AD). The
      molecules responsible for such neurodegeneration in AD brain are mostly unknown.
      Recent findings indicate that the BH3-only proteins of the Bcl-2 family play an
      essential role in various cell death paradigms, including neurodegeneration. Here
      we report that Puma (p53-up-regulated modulator of apoptosis), an important
      member of the BH3-only protein family, is up-regulated in neurons upon toxic beta
      amyloid 1-42 (Abeta(1-42)) exposure both in vitro and in vivo. Down-regulation of
      Puma by specific siRNA provides significant protection against neuron death
      induced by Abeta(1-42). We further demonstrate that the activation of p53 and
      inhibition of PI3K/Akt pathways induce Puma. The transcription factor FoxO3a,
      which is activated when PI3K/Akt signaling is inhibited, directly binds with the
      Puma gene and induces its expression upon exposure of neurons to oligomeric
      Abeta(1-42). Moreover, Puma cooperates with another BH3-only protein, Bim, which
      is already implicated in AD. Our results thus suggest that Puma is activated by
      both p53 and PI3K/Akt/FoxO3a pathways and cooperates with Bim to induce neuron
      death in response to Abeta(1-42). 

PMID- 24567337
TI  - Separate cyclic AMP sensors for neuritogenesis, growth arrest, and survival of
      neuroendocrine cells.
AB  - Dividing neuroendocrine cells differentiate into a neuronal-like phenotype in
      response to ligands activating G protein-coupled receptors, leading to the
      elevation of the second messenger cAMP. Growth factors that act at receptor
      tyrosine kinases, such as nerve growth factor, also cause differentiation. We
      report here that two aspects of cAMP-induced differentiation, neurite extension
      and growth arrest, are dissociable at the level of the sensors conveying the cAMP
      signal in PC12 and NS-1 cells. Following cAMP elevation, neuritogenic cyclic AMP
      sensor/Rapgef2 is activated for signaling to ERK to mediate neuritogenesis,
      whereas Epac2 is activated for signaling to the MAP kinase p38 to mediate growth
      arrest. Neither action of cAMP requires transactivation of TrkA, the receptor for
      NGF. In fact, the differentiating effects of NGF do not require activation of any
      of the cAMP sensors protein kinase A, Epac, or neuritogenic cyclic AMP
      sensor/Rapgef2 but, rather, depend on ERK and p38 activation via completely
      independent signaling pathways. Hence, cAMP- and NGF-dependent signaling for
      differentiation are also completely insulated from each other. Cyclic AMP and NGF
      also protect NS-1 cells from serum withdrawal-induced cell death, again by two
      wholly separate signaling mechanisms, PKA-dependent for cAMP and PKA-independent
      for NGF. 

PMID- 24567338
TI  - Identification of target binding site in photoreceptor guanylyl cyclase
      activating protein 1 (GCAP1).
AB  - Retinal guanylyl cyclase (RetGC)-activating proteins (GCAPs) regulate visual
      photoresponse and trigger congenital retinal diseases in humans, but GCAP
      interaction with its target enzyme remains obscure. We mapped GCAP1 residues
      comprising the RetGC1 binding site by mutagenizing the entire surface of GCAP1
      and testing the ability of each mutant to bind RetGC1 in a cell-based assay and
      to activate it in vitro. Mutations that most strongly affected the activation of
      RetGC1 localized to a distinct patch formed by the surface of non-metal-binding
      EF-hand 1, the loop and the exiting helix of EF-hand 2, and the entering helix of
      EF-hand 3. Mutations in the binding patch completely blocked activation of the
      cyclase without affecting Ca(2+) binding stoichiometry of GCAP1 or its tertiary
      fold. Exposed residues in the C-terminal portion of GCAP1, including EF-hand 4
      and the helix connecting it with the N-terminal lobe of GCAP1, are not critical
      for activation of the cyclase. GCAP1 mutants that failed to activate RetGC1 in
      vitro were GFP-tagged and co-expressed in HEK293 cells with mOrange-tagged RetGC1
      to test their direct binding in cyto. Most of the GCAP1 mutations introduced into
      the "binding patch" prevented co-localization with RetGC1, except for Met-26, Lys
      85, and Trp-94. With these residues mutated, GCAP1 completely failed to stimulate
      cyclase activity but still bound RetGC1 and competed with the wild type GCAP1.
      Thus, RetGC1 activation by GCAP1 involves establishing a tight complex through
      the binding patch with an additional activation step involving Met-26, Lys-85,
      and Trp-94. 

PMID- 24567340
TI  - Nasal endoscopy is recommended for diagnosing adults with chronic rhinosinusitis.
AB  - OBJECTIVE: To assess the diagnostic value of nasal endoscopic findings in adults
      suspected of chronic rhinosinusitis. DATA SOURCES: PubMed, EMBASE, and the
      Cochrane Library. REVIEW METHODS: A comprehensive search was performed up to
      March 5, 2013. Articles that assessed the diagnostic value of nasal endoscopy in
      adults suspected of chronic rhinosinusitis were included. For selected articles,
      the study design was assessed for directness of evidence and risk of bias.
      Prevalence, positive, and negative predictive values were extracted from reported
      data. RESULTS: Out of 3899 unique publications, we included 3 diagnostic studies
      with a high directness of evidence and a low or moderate risk of bias for data
      extraction. They showed a prevalence of chronic rhinosinusitis (diagnosed with
      computed tomography) of .40 to .56. Compared with posterior probabilities we
      found an added value for ruling in chronic rhinosinusitis by a positive nasal
      endoscopy of 25% to 28% and an added value for ruling out chronic rhinosinusitis
      by a negative nasal endoscopy of 5% to 30%. CONCLUSION AND RECOMMENDATION:
      Computed tomography is not considered necessary in case of a positive nasal
      endoscopy. While nasal endoscopy cannot rule out chronic rhinosinusitis, we
      advise computed tomography only for patients with a prolonged or complicated
      course of rhinosinusitis.

PMID- 24567339
TI  - NRA-2, a nicalin homolog, regulates neuronal death by controlling surface
      localization of toxic Caenorhabditis elegans DEG/ENaC channels.
AB  - Hyperactivated DEG/ENaCs induce neuronal death through excessive cation influx
      and disruption of intracellular calcium homeostasis. Caenorhabditis elegans
      DEG/ENaC MEC-4 is hyperactivated by the (d) mutation and induces death of touch
      neurons. The analogous substitution in MEC-10 (MEC-10(d)) co-expressed in the
      same neurons is only mildly neurotoxic. We exploited the lower toxicity of MEC
      10(d) to identify RNAi knockdowns that enhance neuronal death. We report here
      that knock-out of the C. elegans nicalin homolog NRA-2 enhances MEC-10(d)-induced
      neuronal death. Cell biological assays in C. elegans neurons show that NRA-2
      controls the distribution of MEC-10(d) between the endoplasmic reticulum and the
      cell surface. Electrophysiological experiments in Xenopus oocytes support this
      notion and suggest that control of channel distribution by NRA-2 is dependent on
      the subunit composition. We propose that nicalin/NRA-2 functions in a quality
      control mechanism to retain mutant channels in the endoplasmic reticulum,
      influencing the extent of neuronal death. Mammalian nicalin may have a similar
      role in DEG/ENaC biology, therefore influencing pathological conditions like
      ischemia. 

PMID- 24567341
TI  - Is carbon nanoparticle useful in thyroid surgery regardless of surgery extent and
      experience?

PMID- 24567343
TI  - ERAS--enhanced recovery after surgery: moving evidence-based perioperative care
      to practice.
AB  - ERAS is the acronym for enhanced recovery after surgery, a term often used to
      describe perioperative care programs that have been shown to improve outcomes
      after major surgery. This article gives a brief history of the development from
      fast-track surgery to ERAS. Today, the full meaning of ERAS goes beyond just a
      protocol for perioperative care with the initiation of a novel multiprofessional,
      multidisciplinary medical society: the Enhanced Recovery After Surgery Society
      for Perioperative Care (www.erassociety.org). The ERAS Society is involved in the
      development of evidence-based guidelines. These guidelines form the basis for an
      implementation program of the ERAS principles to practice. While ERAS was
      initially developed for colonic resections, these principles are being used in a
      range of operations, and there is also a continuous update of care protocols as
      the fields develop. A key mechanism behind the effectiveness of ERAS is the
      dampening of the stress responses to the surgical insult combined with the use of
      treatments that support return of functions that delay recovery in traditional
      care. The article also gives some insights to why the protocols work and reports
      the effects of ERAS protocols. 

PMID- 24567344
TI  - Acute, subchronic, and developmental toxicological properties of lubricating oil
      base stocks.
AB  - Lubricating oil base stocks (LOBs) are substances used in the manufacture of
      finished lubricants and greases. They are produced from residue remaining after
      atmospheric distillation of crude oil that is subsequently fractionated by vacuum
      distillation and additional refining steps. Initial LOB streams that have been
      produced by vacuum distillation but not further refined may contain polycyclic
      aromatic compounds (PACs) and may present carcinogenic hazards. In modern
      refineries, LOBs are further refined by multistep processes including solvent
      extraction and/or hydrogen treatment to reduce the levels of PACs and other
      undesirable constituents. Thus, mildly (insufficiently) refined LOBs are
      potentially more hazardous than more severely (sufficiently) refined LOBs. This
      article discusses the evaluation of LOBs using statistical models based on
      content of PACs; these models indicate that insufficiently refined LOBs
      (potentially carcinogenic LOBs) can also produce systemic and developmental
      effects with repeated dermal exposure. Experimental data were also obtained in
      ten 13-week dermal studies in rats, eight 4-week dermal studies in rabbits, and
      seven dermal developmental toxicity studies with sufficiently refined LOBs
      (noncarcinogenic and commonly marketed) in which no observed adverse effect
      levels for systemic toxicity and developmental toxicity were 1000 to 2000 mg/kg/d
      with dermal exposures, typically the highest dose tested. Results in both oral
      and inhalation developmental toxicity studies were similar. This absence of
      toxicologically relevant findings was consistent with lower PAC content of
      sufficiently refined LOBs. Based on data on reproductive organs with repeated
      dosing and parameters in developmental toxicity studies, sufficiently refined
      LOBs are likely to have little, if any, effect on reproductive parameters. 

PMID- 24567345
TI  - Subchronic and developmental toxicity of aromatic extracts.
AB  - Aromatic extracts (AEs; distillate AEs [DAEs] and residual AEs [RAEs]) are
      complex, highly viscous liquid petroleum streams with variable compositions
      derived by extraction of aromatic compounds from distillate and residual
      petroleum fractions from a vacuum distillation tower, respectively. The DAEs
      generally contain significant amounts of polycyclic aromatic compounds (PACs) and
      are carcinogenic. The RAEs typically contain lower concentrations of biologically
      active PACs. The PACs in refinery streams can cause effects in repeated-dose and
      developmental toxicity studies. In a 13-week dermal study, light paraffinic DAE
      had several dose-related effects involving multiple organs; no-observed-effect
      level was <5 mg/kg/d, with no overt toxicity. Predicted dose-responses at 10%
      (PDR10s), modeled doses causing a 10% effect on sensitive end points based on PAC
      content, ranged from 25 to 78 mg/kg/d for untested paraffinic DAEs. The no
      observed adverse effect level (NOAEL) for developmental toxicity for light
      paraffinic DAE was 5 mg/kg/d. Statistically significant developmental effects at
      higher doses were associated with maternal effects. The PDR10s for developmental
      toxicity of paraffinic DAEs ranged from 7 to >2000 mg/kg/d, reflecting
      differences due to variation in PACs. The NOAELs for RAEs were 500 mg/kg for 90
      day studies and 2000 mg/kg for developmental toxicity. Reproductive toxicity is
      not considered to be a sensitive end point for AEs based on the toxicity tests
      with DAEs, RAEs, and other PAC-containing petroleum substances. In vivo
      micronucleus tests on heavy paraffinic DAE, RAEs, and a range of other petroleum
      substances have been negative. The exception to this general trend was a
      marginally positive response with light paraffinic DAE. Most DAEs are considered
      unlikely to produce chromosomal effects in vivo. 

PMID- 24567348
TI  - Vibrotactile grasping force and hand aperture feedback for myoelectric forearm
      prosthesis users.
AB  - BACKGROUND: User feedback about grasping force and hand aperture is very
      important in object handling with myoelectric forearm prostheses but is lacking
      in current prostheses. Vibrotactile feedback increases the performance of healthy
      subjects in virtual grasping tasks, but no extensive validation on potential
      users has been performed. OBJECTIVES: Investigate the performance of upper-limb
      loss subjects in grasping tasks with vibrotactile stimulation, providing hand
      aperture, and grasping force feedback. STUDY DESIGN: Cross-over trial. METHODS: A
      total of 10 subjects with upper-limb loss performed virtual grasping tasks while
      perceiving vibrotactile feedback. Hand aperture feedback was provided through an
      array of coin motors and grasping force feedback through a single miniature
      stimulator or an array of coin motors. Objects with varying sizes and weights had
      to be grasped by a virtual hand. RESULTS: Percentages correctly applied hand
      apertures and correct grasping force levels were all higher for the vibrotactile
      feedback condition compared to the no-feedback condition. With visual feedback,
      the results were always better compared to the vibrotactile feedback condition.
      Task durations were comparable for all feedback conditions. CONCLUSION:
      Vibrotactile grasping force and hand aperture feedback improves grasping
      performance of subjects with upper-limb loss. However, it should be investigated
      whether this is of additional value in daily-life tasks. CLINICAL RELEVANCE: This
      study is a first step toward the implementation of sensory vibrotactile feedback
      for users of myoelectric forearm prostheses. Grasping force feedback is crucial
      for optimal object handling, and hand aperture feedback is essential for
      reduction of required visual attention. Grasping performance with feedback is
      evaluated for the potential users.

PMID- 24567349
TI  - Ankle foot orthosis-footwear combination tuning: an investigation into common
      clinical practice in the United Kingdom.
AB  - BACKGROUND: Ankle foot orthoses are used to treat a wide variety of gait
      pathologies. Ankle foot orthosis-footwear combination tuning should be routine
      clinical practice when prescribing an ankle foot orthosis. Current research
      suggests that failure to tune ankle foot orthosis-footwear combinations can lead
      to immediate detrimental effect on function, and in the longer term, it may
      actually contribute to deterioration. OBJECTIVES: The purpose of this preliminary
      study was to identify the current level of knowledge clinicians have in the
      United Kingdom regarding ankle foot orthosis-footwear combination tuning and to
      investigate common clinical practice regarding ankle foot orthosis-footwear
      combination tuning among UK orthotists. STUDY DESIGN: Cross-sectional survey.
      METHODS: A prospective study employing a multi-item questionnaire was sent out to
      registered orthotists and uploaded on to the official website of British
      Association of Prosthetists and Orthotists to be accessed by their members.
      RESULTS: A total of 41 completed questionnaires were received. The results
      demonstrate that only 50% of participants use ankle foot orthosis-footwear
      combination tuning as standard clinical practice. The most prevalent factors
      preventing participants from carrying out ankle foot orthosis-footwear
      combination tuning are a lack of access to three-dimensional gait analysis
      equipment (37%) and a lack of time available in their clinics (27%). CLINICAL
      RELEVANCE: Although, ankle foot orthosis-footwear combination tuning has been
      identified as an essential aspect of the prescription of ankle foot orthoses, the
      results of this study show a lack of understanding of the key principles behind
      ankle foot orthosis-footwear combination tuning.

PMID- 24567350
TI  - A baculovirus-expressed dicistrovirus that is infectious to aphids.

PMID- 24567352
TI  - Paraoxonase lactonase activity, inflammation and antioxidant status in plasma of
      patients with type 1 diabetes mellitus.
AB  - OBJECTIVES: To investigate paraoxonase-1 (PON1) lactonase activity,
      myeloperoxidase (MPO) activity (as a marker of inflammation) and antioxidant
      status in plasma of patients with type 1 diabetes mellitus. METHODS: Whole blood
      and plasma samples were collected from patients with diabetes and healthy control
      subjects. PON1 lactonase and MPO activities and total antioxidant capacity (TEAC)
      were determined in plasma. Glycosylated haemoglobin (HbA1c) was quantified in
      whole blood. RESULTS: Plasma PON1 lactonase and MPO activities were significantly
      higher and TEAC was significantly lower in patients with diabetes (n = 18)
      compared with healthy control subjects (n = 20). There were significant positive
      correlations between PON1 lactonase activity and MPO activity and HbA1c level,
      and plasma MPO and HbA1c. There were significant negative correlations between
      PON1 lactonase activity and TEAC, and MPO activity and TEAC. CONCLUSIONS:
      Increased lactonase activity may inefficiently compensate for the high level of
      chronic inflammation and low antioxidant capacity in the plasma of patients with
      type 1 diabetes mellitus.

PMID- 24567353
TI  - Protocadherin 17 promoter methylation in tumour tissue from patients with bladder
      transitional cell carcinoma.
AB  - OBJECTIVE: To investigate the clinical significance of protocadherin 17 (PCDH17)
      promoter methylation in bladder cancer. METHODS: Methylation-specific polymerase
      chain reaction was used to examine the promoter methylation status of PCDH17 in
      tumour tissue specimens obtained from patients with bladder cancer, and in normal
      bladder epithelial tissue specimens obtained from age- and sex-matched controls.
      The correlations between methylation status and demographic and
      clinicopathological parameters, and disease outcome, were assessed. RESULTS:
      Methylation of the PCDH17 promoter was detected in 77/115 (67.0%) patients with
      bladder cancer and 0/43 (0%) of the controls. Methylation was significantly
      associated with high cancer grade (G3), advanced cancer stage (T2-T4), large
      tumour diameter (> 3 cm) and tumour recurrence. Methylation was also associated
      with significantly shorter survival time compared with unmethylated PCDH17 in
      patients with bladder cancer, and was an independent predictor of overall
      survival. CONCLUSIONS: PCDH17 promoter methylation is closely associated with
      bladder cancer malignancy and may be used as an independent predictor of clinical
      outcomes in patients with bladder cancer.

PMID- 24567354
TI  - Investigation of neutrophil lymphocyte ratio and blood glucose regulation in
      patients with type 2 diabetes mellitus.
AB  - OBJECTIVE: Leukocytosis is thought to be directly associated with the
      pathogenesis of atherosclerosis and metabolic syndrome. Increased white blood
      cell (WBC) count is related to cardiovascular disease in patients with type 2
      diabetes mellitus; raised neutrophil lymphocyte ratio (NLR) is associated with
      metabolic syndrome. There is little information, however, concerning a
      correlation between glycosylated haemoglobin (HbA1c) and NLR. The aim of the
      present study was to investigate the relationship between NLR and blood glucose
      regulation. METHODS: This retrospective study was conducted in patients with type
      2 diabetes mellitus, divided into two groups according to HbA1c levels: group 1,
      HbA1c levels <= 7%; group 2, HbA1c levels > 7%. Venous WBC, neutrophil and
      lymphocyte counts were determined. RESULTS: Of 71 patients included, fasting
      serum glucose, neutrophil and WBC counts were significantly higher in group 2
      compared with group 1. NLR had a positive correlation with HbA1c. CONCLUSION:
      There may be a significant relationship between NLR and blood glucose regulation.
      The authors propose that increased NLR may be associated with elevated HbA1c in
      patients with type 2 diabetes mellitus.

PMID- 24567355
TI  - Ectopic expression of Sonic Hedgehog in a cryptorchid man with azoospermia: a
      case report.
AB  - A 30-year-old man presented with a left undescended testis, right testicular
      deficiency and azoospermia. Testicular biopsy revealed an absence of
      spermatocytes and increased numbers of Leydig cells in the undescended testis.
      Additional comparative analyses were undertaken to explore Sonic Hedgehog (Shh)
      immunostaining in the testis of juvenile and adult mice, in the testis of the
      patient with cryptorchidism, and in archival testicular tissue from a patient
      with obstructive azoospermia and a patient with prostate cancer. Shh
      immunostaining was demonstrated in spermatocytes in juvenile and adult mouse
      testis and in the patients with obstructive azoospermia and prostate cancer,
      suggesting that Shh signalling is involved in normal spermatogenesis. In the
      patient with cryptorchidism, Shh immunostaining was localized to the Leydig
      cells, which suggests that Shh might be involved in the abnormal expansion of the
      Leydig cell population in the testis. These preliminary data on the appearance of
      Shh protein during normal spermatogenesis might provide the basis for further
      investigations to clarify the role of Shh signalling in spermatogenesis during
      normal and pathogenic testis development. 

PMID- 24567356
TI  - MarvelD3 couples tight junctions to the MEKK1-JNK pathway to regulate cell
      behavior and survival.
AB  - MarvelD3 is a transmembrane component of tight junctions, but there is little
      evidence for a direct involvement in the junctional permeability barrier. Tight
      junctions also regulate signaling mechanisms that guide cell proliferation;
      however, the transmembrane components that link the junction to such signaling
      pathways are not well understood. In this paper, we show that MarvelD3 is a
      dynamic junctional regulator of the MEKK1-c-Jun NH2-terminal kinase (JNK)
      pathway. Loss of MarvelD3 expression in differentiating Caco-2 cells resulted in
      increased cell migration and proliferation, whereas reexpression in a metastatic
      tumor cell line inhibited migration, proliferation, and in vivo tumor formation.
      Expression levels of MarvelD3 inversely correlated with JNK activity, as MarvelD3
      recruited MEKK1 to junctions, leading to down-regulation of JNK phosphorylation
      and inhibition of JNK-regulated transcriptional mechanisms. Interplay between
      MarvelD3 internalization and JNK activation tuned activation of MEKK1 during
      osmotic stress, leading to junction dissociation and cell death in MarvelD3
      depleted cells. MarvelD3 thus couples tight junctions to the MEKK1-JNK pathway to
      regulate cell behavior and survival. 

PMID- 24567357
TI  - Senescence-inducing stress promotes proteolysis of phosphoglycerate mutase via
      ubiquitin ligase Mdm2.
AB  - Despite the well-documented clinical significance of the Warburg effect, it
      remains unclear how the aggressive glycolytic rates of tumor cells might
      contribute to other hallmarks of cancer, such as bypass of senescence. Here, we
      report that, during oncogene- or DNA damage-induced senescence, Pak1-mediated
      phosphorylation of phosphoglycerate mutase (PGAM) predisposes the glycolytic
      enzyme to ubiquitin-mediated degradation. We identify Mdm2 as a direct binding
      partner and ubiquitin ligase for PGAM in cultured cells and in vitro. Mutations
      in PGAM and Mdm2 that abrogate ubiquitination of PGAM restored the proliferative
      potential of primary cells under stress conditions and promoted neoplastic
      transformation. We propose that Mdm2, a downstream effector of p53, attenuates
      the Warburg effect via ubiquitination and degradation of PGAM. 

PMID- 24567358
TI  - Caveolae regulate the nanoscale organization of the plasma membrane to remotely
      control Ras signaling.
AB  - The molecular mechanisms whereby caveolae exert control over cellular signaling
      have to date remained elusive. We have therefore explored the role caveolae play
      in modulating Ras signaling. Lipidomic and gene array analyses revealed that
      caveolin-1 (CAV1) deficiency results in altered cellular lipid composition, and
      plasma membrane (PM) phosphatidylserine distribution. These changes correlated
      with increased K-Ras expression and extensive isoform-specific perturbation of
      Ras spatial organization: in CAV1-deficient cells K-RasG12V nanoclustering and
      MAPK activation were enhanced, whereas GTP-dependent lateral segregation of H-Ras
      was abolished resulting in compromised signal output from H-RasG12V nanoclusters.
      These changes in Ras nanoclustering were phenocopied by the down-regulation of
      Cavin1, another crucial caveolar structural component, and by acute loss of
      caveolae in response to increased osmotic pressure. Thus, we postulate that
      caveolae remotely regulate Ras nanoclustering and signal transduction by
      controlling PM organization. Similarly, caveolae transduce mechanical stress into
      PM lipid alterations that, in turn, modulate Ras PM organization. 

PMID- 24567359
TI  - Nuclear lamin stiffness is a barrier to 3D migration, but softness can limit
      survival.
AB  - Cell migration through solid tissue often involves large contortions of the
      nucleus, but biological significance is largely unclear. The nucleoskeletal
      protein lamin-A varies both within and between cell types and was shown here to
      contribute to cell sorting and survival in migration through constraining
      micropores. Lamin-A proved rate-limiting in 3D migration of diverse human cells
      that ranged from glioma and adenocarcinoma lines to primary mesenchymal stem
      cells (MSCs). Stoichiometry of A- to B-type lamins established an activation
      barrier, with high lamin-A:B producing extruded nuclear shapes after migration.
      Because the juxtaposed A and B polymer assemblies respectively conferred viscous
      and elastic stiffness to the nucleus, subpopulations with different A:B levels
      sorted in 3D migration. However, net migration was also biphasic in lamin-A, as
      wild-type lamin-A levels protected against stress-induced death, whereas deep
      knockdown caused broad defects in stress resistance. In vivo xenografts proved
      consistent with A:B-based cell sorting, and intermediate A:B-enhanced tumor
      growth. Lamins thus impede 3D migration but also promote survival against
      migration-induced stresses. 

PMID- 24567360
TI  - Trim32 reduces PI3K-Akt-FoxO signaling in muscle atrophy by promoting plakoglobin
      PI3K dissociation.
AB  - Activation of the PI3K-Akt-FoxO pathway induces cell growth, whereas its
      inhibition reduces cell survival and, in muscle, causes atrophy. Here, we report
      a novel mechanism that suppresses PI3K-Akt-FoxO signaling. Although skeletal
      muscle lacks desmosomes, it contains multiple desmosomal components, including
      plakoglobin. In normal muscle plakoglobin binds the insulin receptor and PI3K
      subunit p85 and promotes PI3K-Akt-FoxO signaling. During atrophy, however, its
      interaction with PI3K-p85 is reduced by the ubiquitin ligase Trim32 (tripartite
      motif containing protein 32). Inhibition of Trim32 enhanced plakoglobin binding
      to PI3K-p85 and promoted PI3K-Akt-FoxO signaling. Surprisingly, plakoglobin
      overexpression alone enhanced PI3K-Akt-FoxO signaling. Furthermore, Trim32
      inhibition in normal muscle increased PI3K-Akt-FoxO signaling, enhanced glucose
      uptake, and induced fiber growth, whereas plakoglobin down-regulation reduced
      PI3K-Akt-FoxO signaling, decreased glucose uptake, and caused atrophy. Thus, by
      promoting plakoglobin-PI3K dissociation, Trim32 reduces PI3K-Akt-FoxO signaling
      in normal and atrophying muscle. This mechanism probably contributes to insulin
      resistance during fasting and catabolic diseases and perhaps to the myopathies
      and cardiomyopathies seen with Trim32 and plakoglobin mutations. 

PMID- 24567361
TI  - Fission of SNX-BAR-coated endosomal retrograde transport carriers is promoted by
      the dynamin-related protein Vps1.
AB  - Retromer is an endosomal sorting device that orchestrates capture and packaging
      of cargo into transport carriers coated with sorting nexin BAR domain proteins
      (SNX-BARs). We report that fission of retromer SNX-BAR-coated tubules from yeast
      endosomes is promoted by Vps1, a dynamin-related protein that localizes to
      endosomes decorated by retromer SNX-BARs and Mvp1, a SNX-BAR that is homologous
      to human SNX8. Mvp1 exhibits potent membrane remodeling activity in vitro, and it
      promotes association of Vps1 with the endosome in vivo. Retrograde transport
      carriers bud from the endosome coated by retromer and Mvp1, and cargo export is
      deficient in mvp1- and vps1-null cells, but with distinct endpoints; cargo export
      is delayed in mvp1-null cells, but cargo export completely fails in vps1-null
      cells. The results indicate that Mvp1 promotes Vps1-mediated fission of retromer-
      and Mvp1-coated tubules that bud from the endosome, revealing a functional link
      between the endosomal sorting and fission machineries to produce retrograde
      transport carriers. 

PMID- 24567362
TI  - A Bub1-Mad1 interaction targets the Mad1-Mad2 complex to unattached kinetochores
      to initiate the spindle checkpoint.
AB  - Recruitment of Mad1-Mad2 complexes to unattached kinetochores is a central event
      in spindle checkpoint signaling. Despite its importance, the mechanism that
      recruits Mad1-Mad2 to kinetochores is unclear. In this paper, we show that MAD-1
      interacts with BUB-1 in Caenorhabditis elegans. Mutagenesis identified specific
      residues in a segment of the MAD-1 coiled coil that mediate the BUB-1
      interaction. In addition to unattached kinetochores, MAD-1 localized between
      separating meiotic chromosomes and to the nuclear periphery. Mutations in the MAD
      1 coiled coil that selectively disrupt interaction with BUB-1 eliminated MAD-1
      localization to unattached kinetochores and between meiotic chromosomes, both of
      which require BUB-1, and abrogated checkpoint signaling. The identified MAD-1
      coiled-coil segment interacted with a C-terminal region of BUB-1 that contains
      its kinase domain, and mutations in this region prevented MAD-1 kinetochore
      targeting independently of kinase activity. These results delineate an
      interaction between BUB-1 and MAD-1 that targets MAD-1-MAD-2 complexes to
      kinetochores and is essential for spindle checkpoint signaling. 

PMID- 24567364
TI  - The Neuropsychological Profile of Comorbid Post-Traumatic Stress Disorder in
      Adult ADHD.
AB  - OBJECTIVE: ADHD and post-traumatic stress disorder (PTSD) are often comorbid yet
      despite the increased comorbidity between the two disorders, to our knowledge, no
      data have been published regarding the neuropsychological profile of adults with
      comorbid ADHD and PTSD. Likewise, previous empirical studies of the
      neuropsychology of PTSD did not control for ADHD status. We sought to fill this
      gap in the literature and to assess the extent to which neuropsychological test
      performance predicted psychosocial functioning, and perceived quality of life.
      METHOD: Participants were 201 adults with ADHD attending an outpatient mental
      health clinic between 1998 and 2003 and 123 controls without ADHD. Participants
      completed a large battery of self-report measures and psychological tests.
      Diagnoses were made using data obtained from structured psychiatric interviews
      (i.e., Structured Clinical Interview for DSM-IV, Schedule for Affective Disorders
      and Schizophrenia for School-Age Children Epidemiologic Version). RESULTS:
      Differences emerged between control participants and participants with ADHD on
      multiple neuropsychological tests. Across all tests, control participants
      outperformed participants with ADHD. Differences between the two ADHD groups
      emerged on seven psychological subtests including multiple Wechsler Adult
      Intelligence Scale-Third edition and Rey-Osterrieth Complex Figure Test measures.
      These test differences did not account for self-reported quality of life
      differences between groups. CONCLUSION: The comorbidity with PTSD in adults with
      ADHD is associated with weaker cognitive performance on several tasks that appear
      related to spatial/perceptual abilities and fluency. Neuropsychological test
      performances may share variance with the quality of life variables yet are not
      mediators of the quality of life ratings.

PMID- 24567363
TI  - Arp5 is a key regulator of myocardin in smooth muscle cells.
AB  - Myocardin (Myocd) and Myocd-related transcription factors (MRTFs) are robust
      coactivators of serum response factor (SRF). RPEL motifs are monomeric globular
      actin (G-actin) binding elements that regulate MRTF localization and activity.
      However, the function of the RPEL motif in Myocd is largely unknown because of
      its low affinity for G-actin. Here, we demonstrated that the Myocd RPEL motif
      bound to actin-related protein 5 (Arp5) instead of conventional actin, resulting
      in a significant suppression of Myocd activity. In addition, Arp5 bound to a DNA
      binding domain of SRF via its C-terminal sequence and prevented the association
      of the Myocd-SRF complex with the promoter regions of smooth muscle genes. Well
      differentiated smooth muscle cells mainly expressed a specific splicing variant
      of arp5; therefore, the protein level of Arp5 was markedly reduced by partial
      messenger RNA decay and translational suppression. In dedifferentiated smooth
      muscle cells, Arp5 knockdown restored the differentiated phenotype via Myocd
      activation. Thus, Arp5 is a key regulator of Myocd activity. 

PMID- 24567365
TI  - Regional Brain Volumes and ADHD Symptoms in Middle-Aged Adults: The PATH Through
      Life Study.
AB  - OBJECTIVE: We investigated whether volumetric differences in ADHD-associated
      brain regions are related to current symptoms of inattention and hyperactivity in
      healthy middle-aged adults and whether co-occurring anxiety/depression symptoms
      moderate these relationships. METHOD: ADHD Self-Report Scale and Brief Patient
      Health Questionnaire were used to assess current symptoms of inattention,
      hyperactivity, anxiety, and depression in a population-based sample ( n = 269).
      Brain volumes, measured using a semi-automated method, were analyzed using
      multiple regression and structural equation modeling to evaluate brain volume
      inattention/hyperactivity symptom relationships for selected regions. RESULTS:
      Volumes of the left nucleus accumbens and a region overlapping the dorsolateral
      prefrontal cortex were positively associated with inattention symptoms. Left
      hippocampal volume was negatively associated with hyperactivity symptoms. The
      brain volume-inattention/hyperactivity symptom associations were stronger when
      anxiety/depression symptoms were controlled for. CONCLUSION: Inattention and
      hyperactivity symptoms in middle-aged adults are associated with different brain
      regions and co-occurring anxiety/depression symptoms moderate these brain
      behavior relationships.

PMID- 24567366
TI  - DOC-MEK: a double-blind randomized phase II trial of docetaxel with or without
      selumetinib in wild-type BRAF advanced melanoma.
AB  - BACKGROUND: Treatment options for wild-type BRAF melanoma patients remain
      limited. Selumetinib, a MEK 1/2 inhibitor, suppresses pERK levels independent of
      BRAF and NRAS mutation status, and combination with docetaxel has demonstrated
      synergy in xenograft models. The aim of this study was to assess the efficacy and
      safety of selumetinib plus docetaxel as first-line treatment in patients with
      wild-type BRAF advanced melanoma. PATIENTS AND METHODS: In this double-blind
      multicentre phase II trial patients with wild-type BRAF melanoma were randomized
      (1:1) to docetaxel with selumetinib or placebo. Docetaxel 75 mg/m(2) was
      administered intravenously every 3 weeks up to six cycles. Selumetinib 75 mg or
      placebo was given orally twice daily until disease progression or unacceptable
      toxicity. The primary end point was progression-free survival (PFS). Tumour NRAS
      mutation status was analysed retrospectively and correlated with treatment
      outcomes. RESULTS: Eighty-three patients were randomized to docetaxel plus
      selumetinib (n = 41) or docetaxel plus placebo (n = 42). The PFS hazard ratio
      (HR) (selumetinib:placebo) was 0.75 [90% confidence interval (CI) 0.50-1.14; P =
      0.130], with a median PFS of 4.23 months (90% CI 3.63-6.90) for docetaxel plus
      selumetinib and 3.93 months (90% CI 2.07-4.16) for docetaxel alone. There was no
      significant difference in overall survival. The objective response rate was 32%
      with selumetinib versus 14% with placebo (P = 0.059). In a retrospective subset
      analysis, NRAS mutation status did not affect significantly upon clinical
      outcomes in either arm. The combination of docetaxel and selumetinib could be
      administered effectively to patients with metastatic melanoma, although the
      combination was less well tolerated than docetaxel alone. CONCLUSIONS: The
      combination of docetaxel with selumetinib showed no significant improvement in
      PFS compared with docetaxel alone, although more patients showed a response to
      combination therapy. We found no evidence to support using tumour NRAS mutation
      as a basis for selecting patients for combined MEK inhibitor and chemotherapy.
      CLINICAL TRIAL: DOC-MEK (EudraCT no: 2009-018153-23).

PMID- 24567367
TI  - "Feeling poor": perceived economic position and environmental mastery among older
      Americans.
AB  - OBJECTIVE: This study examines the relationship between perceived economic
      position (PEP), objective socioeconomic status, and environmental mastery among
      older Americans. METHOD: Using data from the National Social Life, Health, and
      Aging Project (NSHAP), I examine (a) whether PEP is associated with environmental
      mastery even after accounting for objective economic status and (b) whether the
      relationship between PEP and mastery varies by reference group (peers,
      Americans). RESULTS: High PEP is associated with higher mastery while low PEP is
      associated with lower mastery, even after controlling for objective economic
      status. In general, the relationship between PEP and mastery does not vary
      whether PEP relative to peers or PEP relative to American families is examined.
      DISCUSSION: These analyses provide insights into the important role of social
      comparisons in the connection between socioeconomic status and psychological well
      being in the later life course.

PMID- 24567368
TI  - Kinases and pseudokinases: lessons from RAF.
AB  - Protein kinases are thought to mediate their biological effects through their
      catalytic activity. The large number of pseudokinases in the kinome and an
      increasing appreciation that they have critical roles in signaling pathways,
      however, suggest that catalyzing protein phosphorylation may not be the only
      function of protein kinases. Using the principle of hydrophobic spine assembly,
      we interpret how kinases are capable of performing a dual function in signaling.
      Its first role is that of a signaling enzyme (classical kinases; canonical),
      while its second role is that of an allosteric activator of other kinases or as a
      scaffold protein for signaling in a manner that is independent of phosphoryl
      transfer (classical pseudokinases; noncanonical). As the hydrophobic spines are a
      conserved feature of the kinase domain itself, all kinases carry an inherent
      potential to play both roles in signaling. This review focuses on the recent
      lessons from the RAF kinases that effectively toggle between these roles and can
      be "frozen" by introducing mutations at their hydrophobic spines. 

PMID- 24567369
TI  - The myc 3' wnt-responsive element suppresses colonic tumorigenesis.
AB  - Mutations in components of the Wnt/beta-catenin signaling pathway are commonly
      found in colorectal cancers, and these mutations cause aberrant expression of
      genes controlled by Wnt-responsive DNA elements (WREs). While the c-Myc proto
      oncogene (Myc) is required for intestinal phenotypes associated with pathogenic
      Wnt/beta-catenin signaling in vivo, the WREs that control Myc expression in this
      setting have yet to be fully described. Previously, we demonstrated that the Myc
      3' WRE was required for intestinal homeostasis and intestinal repair in response
      to damage. Here, we tested the role of the Myc 3' WRE in intestinal tumorigenesis
      using two independent mouse models. In comparison to Apc(Min/+) mice, Apc(Min/+)
      Myc 3' WRE(-/-) mice contained 25% fewer tumors in the small intestine. Deletion
      of the Myc 3' WRE(-/-) in the Apc(Min/+) background resulted in 4-fold more
      colonic tumors. In a model of colitis-associated colorectal cancer, the Myc 3'
      WRE suppressed colonic tumorigenesis, most notably within the cecum. Using
      chromatin immunoprecipitation and transcript analysis of purified colonic crypts,
      we found that the Myc 3' WRE is required for the transcriptional regulation of
      Myc expression in vivo. These results emphasize the critical role of the Myc 3'
      WRE in maintaining homeostatic Myc expression. 

PMID- 24567370
TI  - Simultaneous gene editing by injection of mRNAs encoding transcription activator
      like effector nucleases into mouse zygotes.
AB  - Injection of transcription activator-like effector nucleases (TALEN) mRNAs into
      mouse zygotes transferred into foster mothers efficiently generated founder mice
      with heritable mutations in targeted genes. Immunofluorescence visualization of
      phosphorylated histone 2A (gammaH2AX) combined with fluorescence in situ
      hybridization revealed that TALEN pairs targeting the Agouti locus induced site
      directed DNA breaks in zygotes within 6 h of injection, an activity that
      continued at reduced efficiency in two-cell embryos. TALEN-Agouti mRNAs injected
      into zygotes of brown FvB * C57BL/6 hybrid mice generated completely black pups,
      confirming that mutations were induced prior to, and/or early after, cell
      division. Founder mice, many of which were mosaic, transmitted altered Agouti
      alleles to F1 pups to yield an allelic series of mutant strains. Although
      mutations were targeted to "spacer" sequences flanked by TALEN binding sites,
      larger deletions that extended beyond the TALEN-binding sequences were also
      detected and were similarly inherited through the germ line. Zygotic coinjection
      of TALEN mRNAs directed to the Agouti, miR-205, and the Arf tumor suppressor loci
      yielded pups containing frequent and heritable mutations of two or three genes.
      Simultaneous gene editing in zygotes affords an efficient approach for producing
      mice with compound mutant phenotypes, bypassing constraints of conventional mouse
      knockout technology in embryonic stem cells. 

PMID- 24567372
TI  - Estrogen sulfotransferase/SULT1E1 promotes human adipogenesis.
AB  - Estrogen sulfotransferase (EST/SULT1E1) is known to catalyze the sulfoconjugation
      and deactivation of estrogens. The goal of this study is to determine whether and
      how EST plays a role in human adipogenesis. By using human primary adipose
      derived stem cells (ASCs) and whole-fat tissues from the abdominal subcutaneous
      fat of obese and nonobese subjects, we showed that the expression of EST was low
      in preadipocytes but increased upon differentiation. Overexpression and knockdown
      of EST in ASCs promoted and inhibited differentiation, respectively. The
      proadipogenic activity of EST in humans was opposite to the antiadipogenic effect
      of the same enzyme in rodents. Mechanistically, EST promoted adipogenesis by
      deactivating estrogens. The proadipogenic effect of EST can be recapitulated by
      using an estrogen receptor (ER) antagonist or ERalpha knockdown. In contrast,
      activation of ER in ASCs inhibited adipogenesis by decreasing the recruitment of
      the adipogenic peroxisome proliferator-activated receptor gamma (PPARgamma) onto
      its target gene promoters, whereas ER antagonism increased the recruitment of
      PPARgamma to its target gene promoters. Linear regression analysis revealed a
      positive correlation between the expression of EST and body mass index (BMI), as
      well as a negative correlation between ERalpha expression and BMI. We conclude
      that EST is a proadipogenic factor which may serve as a druggable target to
      inhibit the turnover and accumulation of adipocytes in obese patients. 

PMID- 24567373
TI  - Fusing VE-cadherin to alpha-catenin impairs fetal liver hematopoiesis and lymph
      but not blood vessel formation.
AB  - We have recently shown that genetic replacement of VE-cadherin by a VE-cadherin
      alpha-catenin fusion construct strongly impairs opening of endothelial cell
      contacts during leukocyte extravasation and induction of vascular permeability in
      adult mice. Here we show that this mutation leads to lethality at midgestation on
      a clean C57BL/6 background. Investigating the reasons for embryonic lethality, we
      observed a lack of fetal liver hematopoiesis and severe lymphedema but no
      detectable defects in blood vessel formation and remodeling. As for the
      hematopoiesis defect, VE-cadherin-alpha-catenin affected neither the generation
      of hematopoietic stem and progenitor cells (HSPCs) from hemogenic endothelium nor
      their differentiation into multiple hematopoietic lineages. Instead, HSPCs
      accumulated in the fetal circulation, suggesting that their entry into the fetal
      liver was blocked. Edema formation was caused by disturbed lymphatic vessel
      development. Lymphatic progenitor cells of VE-cadherin-alpha-catenin-expressing
      embryos were able to leave the cardinal vein and migrate to the site of the first
      lymphatic vessel formation, yet subsequently, these cells failed to form large
      lumenized lymphatic vessels. Thus, stabilizing endothelial cell contacts by a
      covalent link between VE-cadherin and alpha-catenin affects recruitment of
      hematopoietic progenitors into the fetal liver and the development of lymph but
      not blood vessels. 

PMID- 24567371
TI  - Clinical targeting of mutated and wild-type protein tyrosine kinases in cancer.
AB  - Clinical therapies for cancer have evolved from toxic, nontargeted agents to
      manageable, highly targeted therapies. Protein tyrosine kinases are a family of
      signaling molecules implicated in nearly every cancer type and are the foundation
      for the development of modern targeted agents. Recent genomic analyses have
      identified activating mutations, translocations, and amplifications of tyrosine
      kinases. Selective targeting of these genetically altered tyrosine kinases has
      resulted in significant clinical advances, including increased patient survival.
      This indicates that altered protein tyrosine kinases are the main drivers of many
      different cancers. However, lost during analyses of genetic lesions are the
      contributions of activated, wild-type kinases on tumor-dependent pathways. New
      approaches in phosphoproteomic technologies have identified several wild-type
      tyrosine kinase activation states, suggesting that non-genetically altered
      kinases can be essential "nodes" for signal transduction. Here, we summarize the
      evidence supporting the common mechanisms of protein tyrosine kinase activation
      in cancer and provide a personal perspective on the kinases BCR-ABL and BTK, as
      well as nonmutated kinase targets in prostate cancer, through our work. We
      outline the mechanisms of tyrosine kinase activation in the absence of direct
      mutation and discuss whether non-genetically altered tyrosine kinases or their
      associated downstream signaling pathways can be effectively targeted. 

PMID- 24567374
TI  - E2/Estrogen receptor/sjogren syndrome-associated autoantigen relieves coactivator
      activator-induced G1/S arrest to promote breast tumorigenicity.
AB  - Coactivator activator (CoAA) is a dual-functional coregulator that regulates
      steroid receptor-mediated transcription and alternative splicing. Previously, we
      have shown that CoAA has tumor-suppressive potential in tumorigenic human kidney
      cells. Here, we uncover a molecular mechanism by which Sjogren syndrome
      associated autoantigen (SSA), an estrogen receptor (ER) coactivator, induces MYC
      oncogene by removing repressive CoAA through E2-dependent degradation of CoAA and
      promotes G(1)/S transition of the cell cycle as well as anchorage-independent
      growth capability of breast cancer cells. We also show that E2 and ER enhance the
      E3 ligase activity of SSA to modulate CoAA through splicing isoform-selective
      ubiquitylation. We propose this as one potential molecular basis for the reduced
      tumor incidence in autoimmune disease patients and suggest SSA as a potential
      therapeutic target to treat breast cancer.

PMID- 24567375
TI  - Climate change mitigation through livestock system transitions.
AB  - Livestock are responsible for 12% of anthropogenic greenhouse gas emissions.
      Sustainable intensification of livestock production systems might become a key
      climate mitigation technology. However, livestock production systems vary
      substantially, making the implementation of climate mitigation policies a
      formidable challenge. Here, we provide results from an economic model using a
      detailed and high-resolution representation of livestock production systems. We
      project that by 2030 autonomous transitions toward more efficient systems would
      decrease emissions by 736 million metric tons of carbon dioxide equivalent per
      year (MtCO2e?y(-1)), mainly through avoided emissions from the conversion of 162
      Mha of natural land. A moderate mitigation policy targeting emissions from both
      the agricultural and land-use change sectors with a carbon price of US$10 per
      tCO2e could lead to an abatement of 3,223 MtCO2e?y(-1). Livestock system
      transitions would contribute 21% of the total abatement, intra- and interregional
      relocation of livestock production another 40%, and all other mechanisms would
      add 39%. A comparable abatement of 3,068 MtCO2e?y(-1) could be achieved also with
      a policy targeting only emissions from land-use change. Stringent climate
      policies might lead to reductions in food availability of up to 200 kcal per
      capita per day globally. We find that mitigation policies targeting emissions
      from land-use change are 5 to 10 times more efficient--measured in "total
      abatement calorie cost"--than policies targeting emissions from livestock only.
      Thus, fostering transitions toward more productive livestock production systems
      in combination with climate policies targeting the land-use change appears to be
      the most efficient lever to deliver desirable climate and food availability
      outcomes.

PMID- 24567376
TI  - Human coding RNA editing is generally nonadaptive.
AB  - Impairment of RNA editing at a handful of coding sites causes severe disorders,
      prompting the view that coding RNA editing is highly advantageous. Recent genomic
      studies have expanded the list of human coding RNA editing sites by more than 100
      times, raising the question of how common advantageous RNA editing is. Analyzing
      1,783 human coding A-to-G editing sites, we show that both the frequency and
      level of RNA editing decrease as the importance of a site or gene increases; that
      during evolution, edited As are more likely than unedited As to be replaced with
      Gs but not with Ts or Cs; and that among nonsynonymously edited As, those that
      are evolutionarily least conserved exhibit the highest editing levels. These and
      other observations reveal the overall nonadaptive nature of coding RNA editing,
      despite the presence of a few sites in which editing is clearly beneficial. We
      propose that most observed coding RNA editing results from tolerable promiscuous
      targeting by RNA editing enzymes, the original physiological functions of which
      remain elusive. 

PMID- 24567377
TI  - Toll-like receptor 10 is involved in induction of innate immune responses to
      influenza virus infection.
AB  - Toll-like receptors (TLRs) play key roles in innate immune recognition of
      pathogen-associated molecular patterns of invading microbes. Among the 10 TLR
      family members identified in humans, TLR10 remains an orphan receptor without
      known agonist or function. TLR10 is a pseudogene in mice and mouse models are
      noninformative in this regard. Using influenza virus infection in primary human
      peripheral blood monocyte-derived macrophages and a human monocytic cell line, we
      now provide previously unidentified evidence that TLR10 plays a role in innate
      immune responses following viral infection. Influenza virus infection increased
      TLR10 expression and TLR10 contributed to innate immune sensing of viral
      infection leading to cytokine induction, including proinflammatory cytokines and
      interferons. TLR10 induction is more pronounced following infection with highly
      pathogenic avian influenza H5N1 virus compared with a low pathogenic H1N1 virus.
      Induction of TLR10 by virus infection requires active virus replication and de
      novo protein synthesis. Culture supernatants of virus-infected cells modestly up
      regulate TLR10 expression in nonvirus-infected cells. Signaling via TLR10 was
      activated by the functional RNA-protein complex of influenza virus leading to
      robust induction of cytokine expression. Taken together, our findings identify
      TLR10 as an important innate immune sensor of viral infection and its role in
      innate immune defense and immunopathology following viral and bacterial pathogens
      deserves attention. 

PMID- 24567378
TI  - Autoantibodies to IgG/HLA class II complexes are associated with rheumatoid
      arthritis susceptibility.
AB  - Specific HLA class II alleles are strongly associated with susceptibility to
      rheumatoid arthritis (RA); however, how HLA class II regulates susceptibility to
      RA has remained unclear. Recently, we found a unique function of HLA class II
      molecules: their ability to aberrantly transport cellular misfolded proteins to
      the cell surface without processing to peptides. Rheumatoid factor (RF) is an
      autoantibody that binds to denatured IgG or Fc fragments of IgG and is detected
      in 70-80% of RA patients but also in patients with other diseases. Here, we
      report that intact IgG heavy chain (IgGH) is transported to the cell surface by
      HLA class II via association with the peptide-binding groove and that IgGH/HLA
      class II complexes are specifically recognized by autoantibodies in RF-positive
      sera from RA patients. In contrast, autoantibodies in RF-positive sera from non
      RA individuals did not bind to IgGH/HLA class II complexes. Of note, a strong
      correlation between autoantibody binding to IgG complexed with certain HLA-DR
      alleles and the odds ratio for that allele's association with RA was observed (r
      = 0.81; P = 4.6 * 10(-5)). Our findings suggest that IgGH complexed with certain
      HLA class II alleles is a target for autoantibodies in RA, which might explain
      why these HLA class II alleles confer susceptibility to RA. 

PMID- 24567381
TI  - Profile of Andrea Rinaldo.

PMID- 24567380
TI  - Radiation dose rates now and in the future for residents neighboring restricted
      areas of the Fukushima Daiichi Nuclear Power Plant.
AB  - Radiation dose rates were evaluated in three areas neighboring a restricted area
      within a 20- to 50-km radius of the Fukushima Daiichi Nuclear Power Plant in
      August-September 2012 and projected to 2022 and 2062. Study participants wore
      personal dosimeters measuring external dose equivalents, almost entirely from
      deposited radionuclides (groundshine). External dose rate equivalents owing to
      the accident averaged 1.03, 2.75, and 1.66 mSv/y in the village of Kawauchi, the
      Tamano area of Soma, and the Haramachi area of Minamisoma, respectively. Internal
      dose rates estimated from dietary intake of radiocesium averaged 0.0058, 0.019,
      and 0.0088 mSv/y in Kawauchi, Tamano, and Haramachi, respectively. Dose rates
      from inhalation of resuspended radiocesium were lower than 0.001 mSv/y. In 2012,
      the average annual doses from radiocesium were close to the average background
      radiation exposure (2 mSv/y) in Japan. Accounting only for the physical decay of
      radiocesium, mean annual dose rates in 2022 were estimated as 0.31, 0.87, and
      0.53 mSv/y in Kawauchi, Tamano, and Haramachi, respectively. The simple and
      conservative estimates are comparable with variations in the background dose, and
      unlikely to exceed the ordinary permissible dose rate (1 mSv/y) for the majority
      of the Fukushima population. Health risk assessment indicates that post-2012
      doses will increase lifetime solid cancer, leukemia, and breast cancer incidences
      by 1.06%, 0.03% and 0.28% respectively, in Tamano. This assessment was derived
      from short-term observation with uncertainties and did not evaluate the first
      year dose and radioiodine exposure. Nevertheless, this estimate provides
      perspective on the long-term radiation exposure levels in the three regions. 

PMID- 24567379
TI  - Oral glycotoxins are a modifiable cause of dementia and the metabolic syndrome in
      mice and humans.
AB  - Age-associated dementia and Alzheimer's disease (AD) are currently epidemic.
      Neither their cause nor connection to the metabolic syndrome (MS) is clear.
      Suppression of deacetylase survival factor sirtuin 1 (SIRT1), a key host defense,
      is a central feature of AD. Age-related MS and diabetes are also causally
      associated with suppressed SIRT1 partly due to oxidant glycotoxins [advanced
      glycation end products (AGEs)]. Changes in the modern diet include excessive
      nutrient-bound AGEs, such as neurotoxic methyl-glyoxal derivatives (MG). To
      determine whether dietary AGEs promote AD, we evaluated WT mice pair-fed three
      diets throughout life: low-AGE (MG(-)), MG-supplemented low-AGE (MG(+)), and
      regular (Reg) chow. Older MG(+)-fed mice, similar to old Reg controls, developed
      MS, increased brain amyloid-beta42, deposits of AGEs, gliosis, and cognitive
      deficits, accompanied by suppressed SIRT1, nicotinamide
      phosphoribosyltransferase, AGE receptor 1, and PPARgamma. These changes were not
      due to aging or caloric intake, as neither these changes nor the MS were present
      in age-matched, pair-fed MG(-) mice. The mouse data were enhanced by significant
      temporal correlations between high circulating AGEs and impaired cognition, as
      well as insulin sensitivity in older humans, in whom dietary and serum MG levels
      strongly and inversely associated with SIRT1 gene expression. The data identify a
      specific AGE (MG) as a modifiable risk factor for AD and MS, possibly acting via
      suppressed SIRT1 and other host defenses, to promote chronic oxidant stress and
      inflammation. Because SIRT1 deficiency in humans is both preventable and
      reversible by AGE reduction, a therapeutic strategy that includes AGE reduction
      may offer a new strategy to combat the epidemics of AD and MS. 

PMID- 24567383
TI  - Agreeing to disagree on climate policy.
AB  - Disagreements about the value of the utility discount rate--the rate at which our
      concern for the welfare of future people declines with their distance from us in
      time--are at the heart of the debate about the appropriate intensity of climate
      policy. Seemingly small differences in the discount rate yield very different
      policy prescriptions, and no consensus "correct" value has been identified. We
      argue that the choice of discount rate is an ethical primitive: there are many
      different legitimate opinions as to its value, and none should receive a
      privileged place in economic analysis of climate policy. Rather, we advocate a
      social choice-based approach in which a diverse set of individual discount rates
      is aggregated into a "representative" rate. We show that performing this
      aggregation efficiently leads to a time-dependent discount rate that declines
      monotonically to the lowest rate in the population. We apply this discounting
      scheme to calculations of the social cost of carbon recently performed by the US
      government and show that it provides an attractive compromise between competing
      ethical positions, and thus provides a possible resolution to the ethical impasse
      in climate change economics.

PMID- 24567382
TI  - Eukaryotic algal phytochromes span the visible spectrum.
AB  - Plant phytochromes are photoswitchable red/far-red photoreceptors that allow
      competition with neighboring plants for photosynthetically active red light. In
      aquatic environments, red and far-red light are rapidly attenuated with depth;
      therefore, photosynthetic species must use shorter wavelengths of light.
      Nevertheless, phytochrome-related proteins are found in recently sequenced
      genomes of many eukaryotic algae from aquatic environments. We examined the
      photosensory properties of seven phytochromes from diverse algae: four
      prasinophyte (green algal) species, the heterokont (brown algal) Ectocarpus
      siliculosus, and two glaucophyte species. We demonstrate that algal phytochromes
      are not limited to red and far-red responses. Instead, different algal
      phytochromes can sense orange, green, and even blue light. Characterization of
      these previously undescribed photosensors using CD spectroscopy supports a
      structurally heterogeneous chromophore in the far-red-absorbing photostate. Our
      study thus demonstrates that extensive spectral tuning of phytochromes has
      evolved in phylogenetically distinct lineages of aquatic photosynthetic
      eukaryotes. 

PMID- 24567384
TI  - Translocation domain mutations affecting cellular toxicity identify the
      Clostridium difficile toxin B pore.
AB  - Disease associated with Clostridium difficile infection is caused by the actions
      of the homologous toxins TcdA and TcdB on colonic epithelial cells. Binding to
      target cells triggers toxin internalization into acidified vesicles, whereupon
      cryptic segments from within the 1,050-aa translocation domain unfurl and insert
      into the bounding membrane, creating a transmembrane passageway to the cytosol.
      Our current understanding of the mechanisms underlying pore formation and the
      subsequent translocation of the upstream cytotoxic domain to the cytosol is
      limited by the lack of information available regarding the identity and
      architecture of the transmembrane pore. Here, through systematic perturbation of
      conserved sites within predicted membrane-insertion elements of the translocation
      domain, we uncovered highly sensitive residues--clustered between amino acids
      1,035 and 1,107--that when individually mutated, reduced cellular toxicity by as
      much as >1,000-fold. We demonstrate that defective variants are defined by
      impaired pore formation in planar lipid bilayers and biological membranes,
      resulting in an inability to intoxicate cells through either apoptotic or
      necrotic pathways. These findings along with the unexpected similarities
      uncovered between the pore-forming "hotspots" of TcdB and the well-characterized
      alpha-helical diphtheria toxin translocation domain provide insights into the
      structure and mechanism of formation of the translocation pore for this important
      class of pathogenic toxins.

PMID- 24567385
TI  - The ecology in the hematopoietic stem cell niche determines the clinical outcome
      in chronic myeloid leukemia.
AB  - Chronic myeloid leukemia (CML) is a blood disease that disrupts normal function
      of the hematopoietic system. Despite the great progress made in terms of
      molecular therapies for CML, there remain large gaps in our understanding. By
      comparing mathematical models that describe CML progression and etiology we
      sought to identify those models that provide the best description of disease
      dynamics and their underlying mechanisms. Data for two clinical outcomes--disease
      remission or relapse--are considered, and we investigate these using Bayesian
      inference techniques throughout. We find that it is not possible to choose
      between the models based on fits to the data alone; however, by studying model
      predictions we can discard models that fail to take niche effects into account.
      More detailed analysis of the remaining models reveals mechanistic differences:
      for one model, leukemia stem cell dynamics determine the disease outcome; and for
      the other model disease progression is determined at the stage of progenitor
      cells, in particular by differences in progenitor death rates. This analysis also
      reveals distinct transient dynamics that will be experimentally accessible, but
      are currently at the limits of what is possible to measure. To resolve these
      differences we need to be able to probe the hematopoietic stem cell niche
      directly. Our analysis highlights the importance of further mapping of the bone
      marrow hematopoietic niche microenvironment as the "ecological" interactions
      between cells in this niche appear to be intricately linked to disease outcome.

PMID- 24567388
TI  - Physical contact influences how much people pay at celebrity auctions.
AB  - Contagion is a form of magical thinking in which people believe that a person's
      immaterial qualities or essence can be transferred to an object through physical
      contact. Here we investigate how a belief in contagion influences the sale of
      celebrity memorabilia. Using data from three high-profile estate auctions, we
      find that people's expectations about the amount of physical contact between the
      object and the celebrity positively predicts the final bids for items that
      belonged to well-liked individuals (e.g., John F. Kennedy) and negatively
      predicts final bids for items that belonged to disliked individuals (e.g.,
      Bernard Madoff). A follow-up experiment further suggests that these effects are
      driven by contagion beliefs: when asked to bid on a sweater owned by a well-liked
      celebrity, participants report that they would pay substantially less if it was
      sterilized before they received it. However, sterilization increases the amount
      they would pay for a sweater owned by a disliked celebrity. These studies suggest
      that magical thinking may still have effects in contemporary Western societies
      and they provide some unique demonstrations of contagion effects on real-world
      purchase decisions. 

PMID- 24567386
TI  - Habenular kisspeptin modulates fear in the zebrafish.
AB  - Kisspeptin, a neuropeptide encoded by the KISS1/Kiss1, and its cognate G protein
      coupled receptor, GPR54 (kisspeptin receptor, Kiss-R), are critical for the
      control of reproduction in vertebrates. We have previously identified two
      kisspeptin genes (kiss1 and kiss2) in the zebrafish, of which kiss1 neurons are
      located in the habenula, which project to the median raphe. kiss2 neurons are
      located in the hypothalamic nucleus and send axonal projections to gonadotropin
      releasing hormone neurons and regulate reproductive functions. However, the
      physiological significance of the Kiss1 expressed in the habenula remains
      unknown. Here we demonstrate the role of habenular Kiss1 in alarm substance (AS)
      induced fear response in the zebrafish. We found that AS-evoked fear experience
      significantly reduces kiss1 and serotonin-related genes (plasmacytoma expressed
      transcript 1 and solute carrier family 6, member 4) in the zebrafish.
      Furthermore, Kiss1 administration suppressed the AS-evoked fear response. To
      further evaluate the role of Kiss1 in fear response, zebrafish Kiss1 peptide was
      conjugated to saporin (SAP) to selectively inactivate Kiss-R1-expressing neurons.
      The Kiss1-SAP injection significantly reduced Kiss1 immunoreactivity and c-fos
      mRNA in the habenula and the raphe compared with control. Furthermore, 3 d after
      Kiss1-SAP injection, the fish had a significantly reduced AS-evoked fear
      response. These findings provide an insight into the role of the habenular
      kisspeptin system in inhibiting fear. 

PMID- 24567387
TI  - MURC/Cavin-4 facilitates recruitment of ERK to caveolae and concentric cardiac
      hypertrophy induced by alpha1-adrenergic receptors.
AB  - The actions of catecholamines on adrenergic receptors (ARs) induce sympathetic
      responses, and sustained activation of the sympathetic nervous system results in
      disrupted circulatory homeostasis. In cardiomyocytes, alpha1-ARs localize to
      flask-shaped membrane microdomains known as "caveolae." Caveolae require both
      caveolin and cavin proteins for their biogenesis and function. However, the
      functional roles and molecular interactions of caveolar components in
      cardiomyocytes are poorly understood. Here, we showed that muscle-restricted
      coiled-coil protein (MURC)/Cavin-4 regulated alpha1-AR-induced cardiomyocyte
      hypertrophy through enhancement of ERK1/2 activation in caveolae. MURC/Cavin-4
      was expressed in the caveolae and T tubules of cardiomyocytes. MURC/Cavin-4
      overexpression distended the caveolae, whereas MURC/Cavin-4 was not essential for
      their formation. MURC/Cavin-4 deficiency attenuated cardiac hypertrophy induced
      by alpha1-AR stimulation in the presence of caveolae. Interestingly, MURC/Cavin-4
      bound to alpha1A- and alpha1B-ARs as well as ERK1/2 in caveolae, and
      spatiotemporally modulated MEK/ERK signaling in response to alpha1-AR
      stimulation. Thus, MURC/Cavin-4 facilitates ERK1/2 recruitment to caveolae and
      efficient alpha1-AR signaling mediated by caveolae in cardiomyocytes, which
      provides a unique insight into the molecular mechanisms underlying caveola
      mediated signaling in cardiac hypertrophy. 

PMID- 24567389
TI  - Using thermal boundary conditions to engineer the quantum state of a bulk magnet.
AB  - The degree of contact between a system and the external environment can alter
      dramatically its proclivity to quantum mechanical modes of relaxation. We show
      that controlling the thermal coupling of cubic-centimeter-sized crystals of the
      Ising magnet LiHo(x)Y(1-x)F4 to a heat bath can be used to tune the system
      between a glassy state dominated by thermal excitations over energy barriers and
      a state with the hallmarks of a quantum spin liquid. Application of a magnetic
      field transverse to the Ising axis introduces both random magnetic fields and
      quantum fluctuations, which can retard and speed the annealing process,
      respectively, thereby providing a mechanism for continuous tuning between the
      destination states. The nonlinear response of the system explicitly demonstrates
      quantum interference between internal and external relaxation pathways.

PMID- 24567390
TI  - Age-dependent changes in prefrontal intrinsic connectivity.
AB  - The prefrontal cortex continues to mature after puberty and into early adulthood,
      mirroring the time course of maturation of cognitive abilities. However, the way
      in which prefrontal activity changes during peri- and postpubertal cortical
      maturation is largely unknown. To address this question, we evaluated the
      developmental stage of peripubertal rhesus monkeys with a series of morphometric,
      hormonal, and radiographic measures, and conducted behavioral and
      neurophysiological tests as the monkeys performed working memory tasks. We
      compared firing rate and the strength of intrinsic functional connectivity
      between neurons in peripubertal vs. adult monkeys. Notably, analyses of spike
      train cross-correlations demonstrated that the average magnitude of functional
      connections measured between neurons was lower overall in the prefrontal cortex
      of peripubertal monkeys compared with adults. The difference resulted because
      negative functional connections (indicative of inhibitory interactions) were
      stronger and more prevalent in peripubertal compared with adult monkeys, whereas
      the positive connections showed similar distributions in the two groups. Our
      results identify changes in the intrinsic connectivity of prefrontal neurons,
      particularly that mediated by inhibition, as a possible substrate for peri- and
      postpubertal advances in cognitive capacity. 

PMID- 24567391
TI  - Trends in structural coverage of the protein universe and the impact of the
      Protein Structure Initiative.
AB  - The exponential growth of protein sequence data provides an ever-expanding body
      of unannotated and misannotated proteins. The National Institutes of Health
      supported Protein Structure Initiative and related worldwide structural genomics
      efforts facilitate functional annotation of proteins through structural
      characterization. Recently there have been profound changes in the taxonomic
      composition of sequence databases, which are effectively redefining the scope and
      contribution of these large-scale structure-based efforts. The faster-growing
      bacterial genomic entries have overtaken the eukaryotic entries over the last 5
      y, but also have become more redundant. Despite the enormous increase in the
      number of sequences, the overall structural coverage of proteins--including
      proteins for which reliable homology models can be generated--on the residue
      level has increased from 30% to 40% over the last 10 y. Structural genomics
      efforts contributed ~50% of this new structural coverage, despite determining
      only ~10% of all new structures. Based on current trends, it is expected that
      ~55% structural coverage (the level required for significant functional insight)
      will be achieved within 15 y, whereas without structural genomics efforts,
      realizing this goal will take approximately twice as long.

PMID- 24567392
TI  - Chemical defenses and resource trade-offs structure sponge communities on
      Caribbean coral reefs.
AB  - Ecological studies have rarely been performed at the community level across a
      large biogeographic region. Sponges are now the primary habitat-forming organisms
      on Caribbean coral reefs. Recent species-level investigations have demonstrated
      that predatory fishes (angelfishes and some parrotfishes) differentially graze
      sponges that lack chemical defenses, while co-occurring, palatable species heal,
      grow, reproduce, or recruit at faster rates than defended species. Our
      prediction, based on resource allocation theory, was that predator removal would
      result in a greater proportion of palatable species in the sponge community on
      overfished reefs. We tested this prediction by performing surveys of sponge and
      fish community composition on reefs having different levels of fishing intensity
      across the Caribbean. A total of 109 sponge species was recorded from 69 sites,
      with the 10 most common species comprising 51.0% of sponge cover (3.6-7.7% per
      species). Nonmetric multidimensional scaling indicated that the species
      composition of sponge communities depended more on the abundance of sponge-eating
      fishes than geographic location. Across all sites, multiple-regression analyses
      revealed that spongivore abundance explained 32.8% of the variation in the
      proportion of palatable sponges, but when data were limited to geographically
      adjacent locations with strongly contrasting levels of fishing pressure (Cayman
      Islands and Jamaica; Curacao, Bonaire, and Martinique), the adjusted R(2) values
      were much higher (76.5% and 94.6%, respectively). Overfishing of Caribbean coral
      reefs, particularly by fish trapping, removes sponge predators and is likely to
      result in greater competition for space between faster-growing palatable sponges
      and endangered reef-building corals. 

PMID- 24567393
TI  - Mycobacterium abscessus cording prevents phagocytosis and promotes abscess
      formation.
AB  - Mycobacterium abscessus is a rapidly growing Mycobacterium causing a wide
      spectrum of clinical syndromes. It now is recognized as a pulmonary pathogen to
      which cystic fibrosis patients have a particular susceptibility. The M. abscessus
      rough (R) variant, devoid of cell-surface glycopeptidolipids (GPLs), causes more
      severe clinical disease than the smooth (S) variant, but the underlying
      mechanisms of R-variant virulence remain obscure. Exploiting the optical
      transparency of zebrafish embryos, we observed that the increased virulence of
      the M. abscessus R variant compared with the S variant correlated with the loss
      of GPL production. The virulence of the R variant involved the massive production
      of serpentine cords, absent during S-variant infection, and the cords initiated
      abscess formation leading to rapid larval death. Cording occurred within the
      vasculature and was highly pronounced in the central nervous system (CNS). It
      appears that M. abscessus is transported to the CNS within macrophages. The
      release of M. abscessus from apoptotic macrophages initiated the formation of
      cords that grew too large to be phagocytized by macrophages or neutrophils. This
      study is a description of the crucial role of cording in the in vivo
      physiopathology of M. abscessus infection and emphasizes cording as a mechanism
      of immune evasion. 

PMID- 24567394
TI  - Causal effect of intergroup contact on exclusionary attitudes.
AB  - The effect of intergroup contact has long been a question central to social
      scientists. As political and technological changes bring increased international
      migration, understanding intergroup contact is increasingly important to
      scientific and policy debates. Unfortunately, limitations in causal inference
      using observational data and the practical inability to experimentally manipulate
      demographic diversity has limited scholars' ability to address the effects of
      intergroup contact. Here, I report the results of a randomized controlled trial
      testing the causal effects of repeated intergroup contact, in which Spanish
      speaking confederates were randomly assigned to be inserted, for a period of
      days, into the daily routines of unknowing Anglo-whites living in homogeneous
      communities in the United States, thus simulating the conditions of demographic
      change. The result of this experiment is a significant shift toward exclusionary
      attitudes among treated subjects. This experiment demonstrates that even very
      minor demographic change causes strong exclusionary reactions. Developed nations
      and politically liberal subnational units are expected to experience a
      politically conservative shift as international migration brings increased
      intergroup contact. 

PMID- 24567395
TI  - Designer receptor manipulations reveal a role of the locus coeruleus
      noradrenergic system in isoflurane general anesthesia.
AB  - Mechanisms driving emergence from general anesthesia are not well understood. The
      noradrenergic brain nucleus locus coeruleus (LC) modulates arousal and may have
      effects on general anesthetic state. Using virally delivered designer receptors
      to specifically control LC norepinephrine (NE) neurons, we investigated the
      causal relationship between LC-NE activity and general anesthetic state under
      isoflurane. Selective activation of LC-NE neurons produced cortical
      electroencephalography (EEG) activation under continuous deep isoflurane
      anesthesia. Specifically, LC-NE activation reduced burst suppression in EEG and
      drove a rightward shift in peak EEG frequency with reduced delta EEG power and
      increased theta EEG power, measures of cortical arousal. LC-NE activation also
      accelerated behavioral emergence from deep isoflurane anesthesia; this was
      prevented with beta or alpha1 noradrenergic antagonists. Moreover, these
      adrenoreceptor antagonists alone were sufficient to markedly potentiate
      anesthetic duration when delivered centrally or peripherally. Induction of
      anesthesia also was retarded by LC-NE activation. Our results demonstrate that
      the LC-NE system strongly modulates the anesthetic state, and that changes in LC
      NE neurotransmission alone can affect the emergence from isoflurane general
      anesthesia. Taken together, these findings extend our understanding of mechanisms
      underlying general anesthesia and cortical arousal, and have significant
      implications for optimizing the clinical safety and management of general
      anesthesia. 

PMID- 24567397
TI  - Quantifying causal mechanisms to determine how protected areas affect poverty
      through changes in ecosystem services and infrastructure.
AB  - To develop effective environmental policies, we must understand the mechanisms
      through which the policies affect social and environmental outcomes.
      Unfortunately, empirical evidence about these mechanisms is limited, and little
      guidance for quantifying them exists. We develop an approach to quantifying the
      mechanisms through which protected areas affect poverty. We focus on three
      mechanisms: changes in tourism and recreational services; changes in
      infrastructure in the form of road networks, health clinics, and schools; and
      changes in regulating and provisioning ecosystem services and foregone production
      activities that arise from land-use restrictions. The contributions of ecotourism
      and other ecosystem services to poverty alleviation in the context of a real
      environmental program have not yet been empirically estimated. Nearly two-thirds
      of the poverty reduction associated with the establishment of Costa Rican
      protected areas is causally attributable to opportunities afforded by tourism.
      Although protected areas reduced deforestation and increased regrowth, these land
      cover changes neither reduced nor exacerbated poverty, on average. Protected
      areas did not, on average, affect our measures of infrastructure and thus did not
      contribute to poverty reduction through this mechanism. We attribute the
      remaining poverty reduction to unobserved dimensions of our mechanisms or to
      other mechanisms. Our study empirically estimates previously unidentified
      contributions of ecotourism and other ecosystem services to poverty alleviation
      in the context of a real environmental program. We demonstrate that, with
      existing data and appropriate empirical methods, conservation scientists and
      policymakers can begin to elucidate the mechanisms through which ecosystem
      conservation programs affect human welfare. 

PMID- 24567396
TI  - Estrogen controls the survival of BRCA1-deficient cells via a PI3K-NRF2-regulated
      pathway.
AB  - Mutations in the tumor suppressor BRCA1 predispose women to breast and ovarian
      cancers. The mechanism underlying the tissue-specific nature of BRCA1's tumor
      suppression is obscure. We previously showed that the antioxidant pathway
      regulated by the transcription factor NRF2 is defective in BRCA1-deficient cells.
      Reactivation of NRF2 through silencing of its negative regulator KEAP1 permitted
      the survival of BRCA1-null cells. Here we show that estrogen (E2) increases the
      expression of NRF2-dependent antioxidant genes in various E2-responsive cell
      types. Like NRF2 accumulation triggered by oxidative stress, E2-induced NRF2
      accumulation depends on phosphatidylinositol 3-kinase-AKT activation.
      Pretreatment of mammary epithelial cells (MECs) with the phosphatidylinositol 3
      kinase inhibitor BKM120 abolishes the capacity of E2 to increase NRF2 protein and
      transcriptional activity. In vivo the survival defect of BRCA1-deficient MECs is
      rescued by the rise in E2 levels associated with pregnancy. Furthermore,
      exogenous E2 administration stimulates the growth of BRCA1-deficient mammary
      tumors in the fat pads of male mice. Our work elucidates the basis of the tissue
      specificity of BRCA1-related tumor predisposition, and explains why oophorectomy
      significantly reduces breast cancer risk and recurrence in women carrying BRCA1
      mutations. 

PMID- 24567398
TI  - How fragmentation and corridors affect wind dynamics and seed dispersal in open
      habitats.
AB  - Determining how widespread human-induced changes such as habitat loss, landscape
      fragmentation, and climate instability affect populations, communities, and
      ecosystems is one of the most pressing environmental challenges. Critical to this
      challenge is understanding how these changes are affecting the movement abilities
      and dispersal trajectories of organisms and what role conservation planning can
      play in promoting movement among remaining fragments of suitable habitat. Whereas
      evidence is mounting for how conservation strategies such as corridors impact
      animal movement, virtually nothing is known for species dispersed by wind, which
      are often mistakenly assumed to not be limited by dispersal. Here, we combine
      mechanistic dispersal models, wind measurements, and seed releases in a large
      scale experimental landscape to show that habitat corridors affect wind dynamics
      and seed dispersal by redirecting and bellowing airflow and by increasing the
      likelihood of seed uplift. Wind direction interacts with landscape orientation to
      determine when corridors provide connectivity. Our results predict positive
      impacts of connectivity and patch shape on species richness of wind-dispersed
      plants, which we empirically illustrate using 12 y of data from our experimental
      landscapes. We conclude that habitat fragmentation and corridors strongly impact
      the movement of wind-dispersed species, which has community-level consequences. 

PMID- 24567399
TI  - G-protein coupled receptor BAI3 promotes myoblast fusion in vertebrates.
AB  - Muscle fibers form as a result of myoblast fusion, yet the cell surface receptors
      regulating this process are unknown in vertebrates. In Drosophila, myoblast
      fusion involves the activation of the Rac pathway by the guanine nucleotide
      exchange factor Myoblast City and its scaffolding protein ELMO, downstream of
      cell-surface cell-adhesion receptors. We previously showed that the mammalian
      ortholog of Myoblast City, DOCK1, functions in an evolutionarily conserved manner
      to promote myoblast fusion in mice. In search for regulators of myoblast fusion,
      we identified the G-protein coupled receptor brain-specific angiogenesis
      inhibitor (BAI3) as a cell surface protein that interacts with ELMO. In cultured
      cells, BAI3 or ELMO1/2 loss of function severely impaired myoblast fusion without
      affecting differentiation and cannot be rescued by reexpression of BAI3 mutants
      deficient in ELMO binding. The related BAI protein family member, BAI1, is
      functionally distinct from BAI3, because it cannot rescue the myoblast fusion
      defects caused by the loss of BAI3 function. Finally, embryonic muscle precursor
      expression of a BAI3 mutant unable to bind ELMO was sufficient to block myoblast
      fusion in vivo. Collectively, our findings provide a role for BAI3 in the relay
      of extracellular fusion signals to their intracellular effectors, identifying it
      as an essential transmembrane protein for embryonic vertebrate myoblast fusion. 

PMID- 24567400
TI  - Obstacles to integrated pest management adoption in developing countries.
AB  - Despite its theoretical prominence and sound principles, integrated pest
      management (IPM) continues to suffer from anemic adoption rates in developing
      countries. To shed light on the reasons, we surveyed the opinions of a large and
      diverse pool of IPM professionals and practitioners from 96 countries by using
      structured concept mapping. The first phase of this method elicited 413 open
      ended responses on perceived obstacles to IPM. Analysis of responses revealed 51
      unique statements on obstacles, the most frequent of which was "insufficient
      training and technical support to farmers." Cluster analyses, based on
      participant opinions, grouped these unique statements into six themes: research
      weaknesses, outreach weaknesses, IPM weaknesses, farmer weaknesses, pesticide
      industry interference, and weak adoption incentives. Subsequently, 163
      participants rated the obstacles expressed in the 51 unique statements according
      to importance and remediation difficulty. Respondents from developing countries
      and high-income countries rated the obstacles differently. As a group, developing
      country respondents rated "IPM requires collective action within a farming
      community" as their top obstacle to IPM adoption. Respondents from high-income
      countries prioritized instead the "shortage of well-qualified IPM experts and
      extensionists." Differential prioritization was also evident among developing
      country regions, and when obstacle statements were grouped into themes. Results
      highlighted the need to improve the participation of stakeholders from developing
      countries in the IPM adoption debate, and also to situate the debate within
      specific regional contexts. 

PMID- 24567401
TI  - Self-assembly of the general membrane-remodeling protein PVAP into sevenfold
      virus-associated pyramids.
AB  - Viruses have developed a wide range of strategies to escape from the host cells
      in which they replicate. For egress some archaeal viruses use a pyramidal
      structure with sevenfold rotational symmetry. Virus-associated pyramids (VAPs)
      assemble in the host cell membrane from the virus-encoded protein PVAP and open
      at the end of the infection cycle. We characterize this unusual supramolecular
      assembly using a combination of genetic, biochemical, and electron microscopic
      techniques. By whole-cell electron cryotomography, we monitored morphological
      changes in virus-infected host cells. Subtomogram averaging reveals the VAP
      structure. By heterologous expression of PVAP in cells from all three domains of
      life, we demonstrate that the protein integrates indiscriminately into virtually
      any biological membrane, where it forms sevenfold pyramids. We identify the
      protein domains essential for VAP formation in PVAP truncation mutants by their
      ability to remodel the cell membrane. Self-assembly of PVAP into pyramids
      requires at least two different, in-plane and out-of-plane, protein interactions.
      Our findings allow us to propose a model describing how PVAP arranges to form
      sevenfold pyramids and suggest how this small, robust protein may be used as a
      general membrane-remodeling system. 

PMID- 24567402
TI  - Task context impacts visual object processing differentially across the cortex.
AB  - Perception reflects an integration of "bottom-up" (sensory-driven) and "top-down"
      (internally generated) signals. Although models of visual processing often
      emphasize the central role of feed-forward hierarchical processing, less is known
      about the impact of top-down signals on complex visual representations. Here, we
      investigated whether and how the observer's goals modulate object processing
      across the cortex. We examined responses elicited by a diverse set of objects
      under six distinct tasks, focusing on either physical (e.g., color) or conceptual
      properties (e.g., man-made). Critically, the same stimuli were presented in all
      tasks, allowing us to investigate how task impacts the neural representations of
      identical visual input. We found that task has an extensive and differential
      impact on object processing across the cortex. First, we found task-dependent
      representations in the ventral temporal and prefrontal cortex. In particular,
      although object identity could be decoded from the multivoxel response within
      task, there was a significant reduction in decoding across tasks. In contrast,
      the early visual cortex evidenced equivalent decoding within and across tasks,
      indicating task-independent representations. Second, task information was
      pervasive and present from the earliest stages of object processing. However,
      although the responses of the ventral temporal, prefrontal, and parietal cortex
      enabled decoding of both the type of task (physical/conceptual) and the specific
      task (e.g., color), the early visual cortex was not sensitive to type of task and
      could only be used to decode individual physical tasks. Thus, object processing
      is highly influenced by the behavioral goal of the observer, highlighting how top
      down signals constrain and inform the formation of visual representations. 

PMID- 24567403
TI  - Anatomy of F1-ATPase powered rotation.
AB  - F1-ATPase, the catalytic complex of the ATP synthase, is a molecular motor that
      can consume ATP to drive rotation of the gamma-subunit inside the ring of three
      alphabeta-subunit heterodimers in 120 degrees  power strokes. To elucidate the
      mechanism of ATPase-powered rotation, we determined the angular velocity as a
      function of rotational position from single-molecule data collected at 200,000
      frames per second with unprecedented signal-to-noise. Power stroke rotation is
      more complex than previously understood. This paper reports the unexpected
      discovery that a series of angular accelerations and decelerations occur during
      the power stroke. The decreases in angular velocity that occurred with the lower
      affinity substrate ITP, which could not be explained by an increase in substrate
      binding dwells, provides direct evidence that rotation depends on substrate
      binding affinity. The presence of elevated ADP concentrations not only increased
      dwells at 35 degrees  from the catalytic dwell consistent with competitive
      product inhibition but also decreased the angular velocity from 85 degrees  to
      120 degrees , indicating that ADP can remain bound to the catalytic site where
      product release occurs for the duration of the power stroke. The angular velocity
      profile also supports a model in which rotation is powered by Van der Waals
      repulsive forces during the final 85 degrees  of rotation, consistent with a
      transition from F1 structures 2HLD1 and 1H8E (Protein Data Bank). 

PMID- 24567404
TI  - Point-of-care diagnostics for noncommunicable diseases using synthetic urinary
      biomarkers and paper microfluidics.
AB  - With noncommunicable diseases (NCDs) now constituting the majority of global
      mortality, there is a growing need for low-cost, noninvasive methods to diagnose
      and treat this class of diseases, especially in resource-limited settings.
      Molecular biomarkers combined with low-cost point-of-care assays constitute a
      potential solution for diagnosing NCDs, but the dearth of naturally occurring,
      predictive markers limits this approach. Here, we describe the design of
      exogenous agents that serve as synthetic biomarkers for NCDs by producing urinary
      signals that can be quantified by a companion paper test. These synthetic
      biomarkers are composed of nanoparticles conjugated to ligand-encoded reporters
      via protease-sensitive peptide substrates. Upon delivery, the nanoparticles
      passively target diseased sites, such as solid tumors or blood clots, where up
      regulated proteases cleave the peptide substrates and release reporters that are
      cleared into urine. The reporters are engineered for detection by sandwich
      immunoassays, and we demonstrate their quantification directly from unmodified
      urine; furthermore, capture antibody specificity allows the probes to be
      multiplexed in vivo and quantified simultaneously by ELISA or paper lateral flow
      assay (LFA). We tailor synthetic biomarkers specific to colorectal cancer, a
      representative solid tumor, and thrombosis, a common cardiovascular disorder, and
      demonstrate urinary detection of these diseases in mouse models by paper
      diagnostic. Together, the LFA and injectable synthetic biomarkers, which could be
      tailored for multiple diseases, form a generalized diagnostic platform for NCDs
      that can be applied in almost any setting without expensive equipment or trained
      medical personnel. 

PMID- 24567406
TI  - Examining how enzymes self-organize in a membrane.

PMID- 24567405
TI  - Niemann-Pick type C2 protein mediating chemical communication in the worker ant.
AB  - Ants are eusocial insects that are found in most regions of the world. Within its
      caste, worker ants are responsible for various tasks that are required for colony
      maintenance. In their chemical communication, alpha-helical carrier proteins,
      odorant-binding proteins, and chemosensory proteins, which accumulate in the
      sensillum lymph in the antennae, play essential roles in transferring hydrophobic
      semiochemicals to chemosensory receptors. It has been hypothesized that
      semiochemicals are recognized by alpha-helical carrier proteins. The number of
      these proteins, however, is not sufficient to interact with a large number of
      semiochemicals estimated from chemosensory receptor genes. Here we shed light on
      this conundrum by identifying a Niemann-Pick type C2 (NPC2) protein from the
      antenna of the worker Japanese carpenter ant, Camponotus japonicus (CjapNPC2).
      CjapNPC2 accumulated in the sensillum cavity in the basiconic sensillum. The
      ligand-binding pocket of CjapNPC2 was composed of a flexible beta-structure that
      allowed it to bind to a wide range of potential semiochemicals. Some of the
      semiochemicals elicited electrophysiolgical responses in the worker antenna. In
      vertebrates, NPC2 acts as an essential carrier protein for cholesterol from late
      endosomes and lysosomes to other cellular organelles. However, the ants have
      evolved an NPC2 with a malleable ligand-binding pocket as a moderately selective
      carrier protein in the sensillum cavity of the basiconic sensillum. CjapNPC2
      might be able to deliver various hydrophobic semiochemicals to chemosensory
      receptor neurons and plays crucial roles in chemical communication required to
      perform the worker ant tasks. 

PMID- 24567407
TI  - Major Facilitator Superfamily (MFS) evolved without 3-transmembrane segment unit
      rearrangements.

PMID- 24567408
TI  - A propagating ATPase gradient drives transport of surface-confined cellular
      cargo.
AB  - The faithful segregation of duplicated genetic material into daughter cells is
      critical to all organisms. In many bacteria, the segregation of chromosomes
      involves transport of "centromere-like" loci over the main body of the
      chromosome, the nucleoid, mediated by a two-protein partition system: a
      nonspecific DNA-binding ATPase, ParA, and an ATPase stimulator, ParB, which binds
      to the centromere-like loci. These systems have previously been proposed to
      function through a filament-based mechanism, analogous to actin- or microtubule
      based movement. Here, we reconstituted the F-plasmid partition system using a DNA
      carpeted flow cell as an artificial nucleoid surface and magnetic beads coated
      with plasmid partition complexes as surface-confined cargo. This minimal system
      recapitulated directed cargo motion driven by a surface ATPase gradient that
      propagated with the cargo. The dynamics are consistent with a diffusion-ratchet
      model, whereby the cargo dynamically establishes, and interacts with, a
      concentration gradient of the ATPase. A chemophoresis force ensues as the cargo
      perpetually chases the ATPase gradient, allowing the cargo to essentially "surf"
      the nucleoid on a continuously traveling wave of the ATPase. Demonstration of
      this non-filament-based motility mechanism in a biological context establishes a
      distinct class of motor system used for the transport and positioning of large
      cellular cargo. 

PMID- 24567409
TI  - Pilus hijacking by a bacterial coaggregation factor critical for oral biofilm
      development.
AB  - The formation of dental plaque, a highly complex biofilm that causes gingivitis
      and periodontitis, requires specific adherence among many oral microbes,
      including the coaggregation of Actinomyces oris with Streptococcus oralis that
      helps to seed biofilm development. Here, we report the discovery of a key
      coaggregation factor for this process. This protein, which we named coaggregation
      factor A (CafA), is one of 14 cell surface proteins with the LPXTG motif
      predicted in A. oris MG1, whose function was hitherto unknown. By systematic
      mutagenesis of each of these genes and phenotypic characterization, we found that
      the Actinomyces/Streptococcus coaggregation is only abolished by deletion of
      cafA. Subsequent biochemical and cytological experiments revealed that CafA
      constitutes the tip of a unique form of the type 2 fimbria long known for its
      role in coaggregation. The direct and predominant role of CafA in adherence is
      evident from the fact that CafA or an antibody against CafA inhibits
      coaggregation, whereas the shaft protein FimA or a polyclonal antibody against
      FimA has no effect. Remarkably, FimA polymerization was blocked by deletion of
      genes for both CafA and FimB, the previously described tip protein of the type 2
      fimbria. Together, these results indicate that some surface proteins not linked
      to a pilus gene cluster in Gram-positive bacteria may hijack the pilus. These
      unique tip proteins displayed on a common pilus shaft may serve distinct
      physiological functions. Furthermore, the pilus shaft assembly in Gram-positive
      bacteria may require a tip, as is true for certain Gram-negative bacterial pili. 

PMID- 24567410
TI  - Loss of mTOR complex 1 induces developmental blockage in early T-lymphopoiesis
      and eradicates T-cell acute lymphoblastic leukemia cells.
AB  - mTOR is an evolutionarily conserved kinase that plays a critical role in sensing
      and responding to environmental determinants. Recent studies have shown that fine
      tuning of the activity of mTOR complexes contributes to organogenesis and
      tumorigenesis. Although rapamycin, an allosteric mTOR inhibitor, is an effective
      immunosuppressant, the precise roles of mTOR complexes in early T-cell
      development remain unclear. Here we show that mTORC1 plays a critical role in the
      development of both early T-cell progenitors and leukemia. Deletion of Raptor, an
      essential component of mTORC1, produced defects in the earliest development of T
      cell progenitors in vivo and in vitro. Deficiency of Raptor resulted in cell
      cycle abnormalities in early T-cell progenitors that were associated with
      instability of the Cyclin D2/D3-CDK6 complexes; deficiency of Rictor, an mTORC2
      component, did not have the same effect, indicating that mTORC1 and -2 control T
      cell development in different ways. In a model of myeloproliferative neoplasm and
      T-cell acute lymphoblastic leukemia (T-ALL) evoked by Kras activation, Raptor
      deficiency dramatically inhibited the cell cycle in oncogenic Kras-expressing T
      cell progenitors, but not myeloid progenitors, and specifically prevented the
      development of T-ALL. Although rapamycin treatment significantly prolonged the
      survival of recipient mice bearing T-ALL cells, rapamycin-insensitive leukemia
      cells continued to propagate in vivo. In contrast, Raptor deficiency in the T-ALL
      model resulted in cell cycle arrest and efficient eradication of leukemia. Thus,
      understanding the cell-context-dependent role of mTORC1 illustrates the potential
      importance of mTOR signals as therapeutic targets. 

PMID- 24567411
TI  - Crystal structures of human soluble adenylyl cyclase reveal mechanisms of
      catalysis and of its activation through bicarbonate.
AB  - cAMP is an evolutionary conserved, prototypic second messenger regulating
      numerous cellular functions. In mammals, cAMP is synthesized by one of 10
      homologous adenylyl cyclases (ACs): nine transmembrane enzymes and one soluble AC
      (sAC). Among these, only sAC is directly activated by bicarbonate (HCO3(-)); it
      thereby serves as a cellular sensor for HCO3(-), carbon dioxide (CO2), and pH in
      physiological functions, such as sperm activation, aqueous humor formation, and
      metabolic regulation. Here, we describe crystal structures of human sAC catalytic
      domains in the apo state and in complex with substrate analog, products, and
      regulators. The activator HCO3(-) binds adjacent to Arg176, which acts as a
      switch that enables formation of the catalytic cation sites. An anionic
      inhibitor, 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid, inhibits sAC
      through binding to the active site entrance, which blocks HCO3(-) activation
      through steric hindrance and trapping of the Arg176 side chain. Finally, product
      complexes reveal small, local rearrangements that facilitate catalysis. Our
      results provide a molecular mechanism for sAC catalysis and cellular HCO3(-)
      sensing and a basis for targeting this system with drugs. 

PMID- 24567414
TI  - Expression of growth arrest-specific protein 6 and Axl molecules in the left
      internal mammary artery of patients undergoing coronary artery bypass grafting.
AB  - AIMS: Studies have demonstrated that using a left internal mammary artery (LIMA)
      graft yields excellent long-term results in coronary artery bypass grafting
      (CABG). The growth arrest-specific 6 (Gas6) gene and its receptor, Axl, are
      crucial in vascular haemostasis and atherosclerosis. The objective of this study
      was to determine the expression of Gas6 and Axl molecules in the aorta and LIMA
      in patients undergoing CABG. METHODS: Plasma and tissue specimens were collected
      from 19 patients undergoing elective CABG. The expression of the Gas6 and Axl in
      the injured aorta and LIMA was examined using reverse transcription PCR (RT-PCR),
      real-time RT-PCR, western blot and immunohistochemical staining. RESULTS: In CABG
      patients, the mRNA, immunoreactivity and protein expressions of the Gas6 and Axl
      were considerably higher in the LIMA than those in the aorta. Further analysis
      revealed that the expression of the Gas6 positively correlated with that of Axl
      in the LIMA and aorta. The plasma Gas6 level was considerably and positively
      correlated with the expression of Gas6 protein in the LIMA and aorta.
      CONCLUSIONS: The present study discovered that the higher expression of Gas6/Axl
      pathway components in the LIMA compared with that in the aorta may partly explain
      the less frequent atherosclerotic events involving the LIMA compared with other
      arteries. Moreover, Gas6 may play a critical and protective role in human
      vascular biology.

PMID- 24567412
TI  - Discovery of two GLP-1/Notch target genes that account for the role of GLP
      1/Notch signaling in stem cell maintenance.
AB  - A stem cell's immediate microenvironment creates an essential "niche" to maintain
      stem cell self-renewal. Many niches and their intercellular signaling pathways
      are known, but for the most part, the key downstream targets of niche signaling
      remain elusive. Here, we report the discovery of two GLP-1/Notch target genes,
      lst-1 (lateral signaling target) and sygl-1 (synthetic Glp), that function
      redundantly to maintain germ-line stem cells (GSCs) in the nematode
      Caenorhabditis elegans. Whereas lst-1 and sygl-1 single mutants appear normal,
      lst-1 sygl-1 double mutants are phenotypically indistinguishable from glp-1/Notch
      mutants. Multiple lines of evidence demonstrate that GLP-1/Notch signaling
      activates lst-1 and sygl-1 expression in GSCs within the niche. Therefore, these
      two genes fully account for the role of GLP-1/Notch signaling in GSC maintenance.
      Importantly, lst-1 and sygl-1 are not required for GLP-1/Notch signaling per se.
      We conclude that lst-1 and sygl-1 forge a critical link between Notch signaling
      and GSC maintenance. 

PMID- 24567415
TI  - A survey of reporting of colorectal cancer in Scotland: compliance with
      guidelines and effect of proforma reporting.
AB  - AIMS: The main purpose of the study was to present a baseline audit of reporting
      of colorectal cancers resection specimens in Scotland, audited against the Royal
      College of Pathologists (RCPath) standards (2007) and NHS Quality Improvement
      Scotland (NHS QIS) standards. METHODS: 50 consecutive rectal and 50 consecutive
      colonic cancer cases from 2011 were audited from 10 Scottish health boards
      involved in colorectal cancer reporting (n=953). The rates of reporting of
      serosal involvement, extramural venous invasion (EMVI) and the mean numbers of
      lymph nodes found were audited against RCPath standards and compared between
      units that routinely used a reporting proforma versus those that did not.
      RESULTS: The performance in reporting of rectal cancer was generally worse than
      for colonic cancer, with only three units meeting the RCPath standards for
      reporting of rectal cancer. There were significant differences between units that
      routinely used a proforma, with the non-proforma group failing to meet the
      minimum standards for both serosal involvement (6%) and EMVI (24%). In the non
      proforma group, 56% of rectal cases had a mean lymph node count of 12 or more
      compared with 81% in the proforma group. CONCLUSIONS: Significant differences
      exist in the frequencies with which important adverse prognostic features are
      reported by pathologists across 10 Scottish health boards. This has potential
      implications for patient care. Health boards that make routine use of reporting
      proformas are more likely to meet RCPath guidelines for reporting of these
      important pathological parameters.

PMID- 24567416
TI  - Factors influencing Internet usage in older adults (65 years and above) living in
      rural and urban Sweden.
AB  - Older adults living in rural and urban areas have shown to distinguish themselves
      in technology adoption; a clearer profile of their Internet use is important in
      order to provide better technological and health-care solutions. Older adults'
      Internet use was investigated across large to midsize cities and rural Sweden.
      The sample consisted of 7181 older adults ranging from 59 to 100 years old.
      Internet use was investigated with age, education, gender, household economy,
      cognition, living alone/or with someone and rural/urban living. Logistic
      regression was used. Those living in rural areas used the Internet less than
      their urban counterparts. Being younger and higher educated influenced Internet
      use; for older urban adults, these factors as well as living with someone and
      having good cognitive functioning were influential. Solutions are needed to avoid
      the exclusion of some older adults by a society that is today being shaped by the
      Internet. 

PMID- 24567417
TI  - Hidradenitis suppurativa: a common and burdensome, yet under-recognised,
      inflammatory skin disease.
AB  - Hidradenitis suppurativa (HS) is a chronic, relapsing, inflammatory skin
      condition that typically occurs after puberty. The primary clinical presentation
      is painful inflamed nodules or boils in the apocrine gland-bearing regions
      (armpits, genital area, groin, breasts and buttocks/anus) that progress to
      abscesses, sinus tracts and scarring. Severity is typically described according
      to three Hurley categories, with most patients having mild or moderate disease.
      Estimated prevalence is 1-4% worldwide and HS is three times more common in women
      than men. Patients' disease burden includes intense pain, work disability and
      overall poor quality of life. Although the clinical signs of the disease can
      often be hidden by clothing, active HS is associated with a malodorous discharge
      that contributes to the disabling social stigma. Risk factors include smoking and
      obesity. Comorbidities include inflammatory bowel disease and
      spondyloarthropathies. The presentation of the disease is distinct, yet HS is not
      well-recognised except in dermatology clinics. 

PMID- 24567418
TI  - Phenol soluble modulin (PSM) variants of community-associated methicillin
      resistant Staphylococcus aureus (MRSA) captured using mass spectrometry-based
      molecular networking.
AB  - Molecular genetic analysis indicates that the problematic human bacterial
      pathogen methicillin-resistant Staphylococcus aureus possesses more than 2000
      open reading frames in its genome. This number of potential gene products,
      coupled with intrinsic mechanisms of posttranslational modification, endows
      methicillin-resistant Staphylococcus aureus with a highly complex biochemical
      repertoire. Recent proteomic and metabolomic advances have provided methodologies
      to better understand and characterize the biosynthetic factors released by
      microbial organisms. Here, the emerging tool of mass spectrometry-based molecular
      networking was used to visualize and map the repertoire of biosynthetic factors
      produced by a community-associated methicillin-resistant Staphylococcus aureus
      strain representative of the epidemic USA300 clone. In particular, the study
      focused on elucidating the complexity of the recently discovered phenol soluble
      modulin family of peptides when placed under various antibiotic treatment
      stresses. Novel PSM truncated variant peptides were captured, and the type of
      variants that were clustered by the molecular networks platform changed in
      response to the different antibiotic treatment conditions. After discovery, a
      group of the peptides were selected for functional analysis in vitro. The
      peptides displayed bioactive properties including the ability to induce
      proinflammatory responses in human THP-1 monocytes. Additionally, the tested
      peptides did not display antimicrobial activity as previously reported for other
      phenol soluble modulin truncated variants. Our findings reveal that the PSM
      family of peptides are quite structurally diverse, and suggest a single phenol
      soluble modulin parent peptide can functionally spawn differential bioactivities
      in response to various external stimuli. 

PMID- 24567420
TI  - Blackouts in the toilet: a case of micturition-induced reflex epilepsy.

PMID- 24567421
TI  - Toward accommodating physicians' conscientious objections: an argument for public
      disclosure.
AB  - This paper aims to demonstrate how public disclosure can be used to balance
      physicians' conscientious objections with their professional obligations to
      patients--specifically respect for patient autonomy and informed consent. It is
      argued here that physicians should be permitted to exercise conscientious
      objections, but that they have a professional obligation to provide advance
      notification to patients about those objections. It is further argued here that
      public disclosure is an appropriate and ethically justifiable limit to the
      principle of advance notification. The argument for publicly disclosing
      physicians' conscientious objections is made in this paper by discussing three
      practical benefits of public disclosure in medicine, and then addressing how
      publicly disclosing physicians' conscientious objections is not an undue invasion
      of privacy. Three additional concerns with public disclosure of physicians'
      conscientious objections are briefly addressed--potential harassment of
      physicians, workplace discrimination, and mischaracterising physicians'
      professional aptitude--concluding that each of these concerns requires further
      deliberation in the realm of business ethics.

PMID- 24567422
TI  - Precedent autonomy should be respected in life-sustaining treatment decisions.
AB  - In the 2011 landmark case of W v M, the English Court of Protection ruled that it
      was unlawful to withdraw artificial nutrition and hydration from a woman who had
      been in a minimally conscious state for 8 years. From the perspective of the
      court, the absence of a written advance directive negated the woman's previous,
      autonomous interests and, consequently, emphasis was given to her current welfare
      and well-being. While life itself is a moral good, prolonging life for a person
      in regular pain with no hope of recovering to a more complete state of awareness
      simply because that person only verbalized her wishes about her treatment
      decisions seems to drastically undervalue the principle of autonomy. We refute
      the notion that it is the role of the court to prolong life insofar as it can and
      argue that withholding and withdrawing life sustaining technologies from patients
      in a minimally conscious state can be ethically justified. 

PMID- 24567423
TI  - The science of politics and the politicization of science.

PMID- 24567419
TI  - Sorbitol dehydrogenase overexpression and other aspects of dysregulated protein
      expression in human precancerous colorectal neoplasms: a quantitative proteomics
      study.
AB  - Colorectal adenomas are cancer precursor lesions of the large bowel. A multitude
      of genomic and epigenomic changes have been documented in these preinvasive
      lesions, but their impact on the protein effectors of biological function has not
      been comprehensively explored. Using shotgun quantitative MS, we exhaustively
      investigated the proteome of 30 colorectal adenomas and paired samples of normal
      mucosa. Total protein extracts were prepared from these tissues (prospectively
      collected during colonoscopy) and from normal (HCEC) and cancerous (SW480, SW620,
      Caco2, HT29, CX1) colon epithelial cell lines. Peptides were labeled with
      isobaric tags (iTRAQ 8-plex), separated via OFFGEL electrophoresis, and analyzed
      by means of LC-MS/MS. Nonredundant protein families (4325 in tissues, 2017 in
      cell lines) were identified and quantified. Principal component analysis of the
      results clearly distinguished adenomas from normal mucosal samples and cancer
      cell lines from HCEC cells. Two hundred and twelve proteins displayed significant
      adenoma-related expression changes (q-value < 0.02, mean fold change versus
      normal mucosa +/-1.4), which correlated (r = 0.74) with similar changes
      previously identified by our group at the transcriptome level. Fifty-one (~25%)
      proteins displayed directionally similar expression changes in colorectal cancer
      cells (versus HCEC cells) and were therefore attributed to the epithelial
      component of adenomas. Although benign, adenomas already exhibited cancer
      associated proteomic changes: 69 (91%) of the 76 protein up-regulations
      identified in these lesions have already been reported in cancers. One of the
      most striking changes involved sorbitol dehydrogenase, a key enzyme in the polyol
      pathway. Validation studies revealed dramatically increased sorbitol
      dehydrogenase concentrations and activity in adenomas and cancer cell lines,
      along with important changes in the expression of other enzymes in the same
      (AKR1B1) and related (KHK) pathways. Dysregulated polyol metabolism might
      represent a novel facet of metabolome remodeling associated with tumorigenesis. 

PMID- 24567424
TI  - Literature as an exploration of the phenomenology of schizophrenia: disorder and
      recovery in Denis Johnson's Jesus' Son.
AB  - When read as a fictional psychosis narrative, Jesus' Son, a collection of short
      stories by Denis Johnson, reveals important elements of the phenomenology of
      schizophrenia and recovery. It is possible that Jesus' Son, as a work of fiction,
      may be able to uniquely add depth and nuance to an understanding of the
      phenomenology of schizophrenia involving a state of psychological fragmentation,
      an ever-changing interpersonal field and a loss of personal agency. In addition,
      by following the protagonist in Jesus' Son as he begins to resolve some of his
      difficulties, the book also offers an individualised account of recovery. The
      authors detail how the book reveals these insights about schizophrenia and
      recovery and suggest that these elements are intertwined in such a manner that
      leads to a profound disruption of self-experience, characterised by a collapse of
      metacognitive processes. Jesus' Son may add depth to our understanding of the
      subjective experience of schizophrenia and recovery, and also may serve as one
      example in which the study of humanities offers an opportunity to explore the
      human elements in the most profound forms of suffering. 

PMID- 24567425
TI  - Socioeconomic inequalities in mortality in 16 European cities.
AB  - AIMS: To explore inequalities in total mortality between small areas of 16
      European cities for men and women, as well as to analyse the relationship between
      these geographical inequalities and their socioeconomic indicators. METHODS: A
      cross-sectional ecological design was used to analyse small areas in 16 European
      cities (26,229,104 inhabitants). Most cities had mortality data for a period
      between 2000 and 2008 and population size data for the same period. Socioeconomic
      indicators included an index of socioeconomic deprivation, unemployment, and
      educational level. We estimated standardised mortality ratios and controlled for
      their variability using Bayesian models. We estimated relative risk of mortality
      and excess number of deaths according to socioeconomic indicators. RESULTS: We
      observed a consistent pattern of inequality in mortality in almost all cities,
      with mortality increasing in parallel with socioeconomic deprivation.
      Socioeconomic inequalities in mortality were more pronounced for men than women,
      and relative inequalities were greater in Eastern and Northern European cities,
      and lower in some Western (men) and Southern (women) European cities. The pattern
      of excess number of deaths was slightly different, with greater inequality in
      some Western and Northern European cities and also in Budapest, and lower among
      women in Madrid and Barcelona. CONCLUSIONS: In this study, we report a consistent
      pattern of socioeconomic inequalities in mortality in 16 European cities. Future
      studies should further explore specific causes of death, in order to determine
      whether the general pattern observed is consistent for each cause of death.

PMID- 24567426
TI  - Semen quality trends in French regions are consistent with a global change in
      environmental exposure.
AB  - A retrospective study carried out recently in a large sample of men, close to the
      general population, has reported a significant and strong decline in sperm
      concentration and morphology in the whole of France between 1989 and 2005. We
      studied these trends within each region of France. Data were obtained from the
      Fivnat database. The study sample comprised male partners of sterile women in
      whom both tubes were absent or blocked. They were located at the assisted
      reproductive technology center. A Bayesian spatio-temporal model with parametric
      time trends, adjusted for age, was used to model overall time trends for each
      region. The results show that sperm concentration decreased in almost all regions
      of France. Among them, Aquitaine showed the highest decrease and Midi-Pyrenees
      had the lowest average for the whole period. Regarding total motility, most
      regions showed a slight increase while Bourgogne showed a steep and significant
      decrease. While considering sperm morphology, there was a decrease in most of the
      regions. The decrease in Aquitaine and Midi-Pyrenees was stronger when compared
      with the overall trend. In conclusion, a decrease in sperm concentration and
      morphology, already shown at the French metropolitan territory level, was
      observed in most regions of France. This is consistent with a global change in
      environmental exposure, according to the endocrine disruptor hypothesis
      especially. Indeed, ubiquitary exposure to chemicals has been growing in the
      general population of France since the 1950s, and the results do not appear to
      support the lifestyle hypothesis. The highest decreases and lowest values are
      consistently observed in two proximate regions that are both highly agricultural
      and densely populated. 

PMID- 24567427
TI  - Kisspeptin modulates fertilization capacity of mouse spermatozoa.
AB  - Kisspeptin acts as an upstream regulator of the hypothalamus-pituitary-gonad
      axis, which is one of the main regulatory systems for mammalian reproduction.
      Kiss1 and its receptor Kiss1r (also known as G protein-coupled receptor 54
      (Gpr54)) are expressed in various organs, but their functions are not well
      understood. The purpose of this study was to investigate the expression profiles
      and functions of kisspeptin and KISS1R in the reproductive tissues of imprinting
      control region mice. To identify the expression pattern and location of
      kisspeptin and KISS1R in gonads, testes and ovarian tissues were examined by
      immunohistochemical or immunofluorescent staining. Kisspeptin and KISS1R were
      expressed primarily in Leydig cells and seminiferous tubules respectively. KISS1R
      was specifically localized in the acrosomal region of spermatids and mature
      spermatozoa. Kisspeptin, but not KISS1R, was expressed in the cumulus-oocyte
      complex and oviductal epithelium of ovarian and oviductal tissues. The sperm
      intracellular calcium concentrations significantly increased in response to
      treatment with kisspeptin 10 in Fluo-4-loaded sperm. The IVF rates decreased
      after treatment of sperm with the kisspeptin antagonist peptide 234. These
      results suggest that kisspeptin and KISS1R might be involved in the fertilization
      process in the female reproductive tract. In summary, this study indicates that
      kisspeptin and KISS1R are expressed in female and male gametes, respectively, and
      in mouse reproductive tissues. These data strongly suggest that the kisspeptin
      system could regulate mammalian fertilization and reproduction.

PMID- 24567428
TI  - Prospective study of fertility concerns and preservation strategies in young
      women with breast cancer.
AB  - PURPOSE: Most research regarding fertility in young women with breast cancer has
      focused on long-term survivors. Little is known about how fertility concerns
      affect treatment decisions or fertility preservation strategies at the time of
      initial cancer diagnosis. PATIENTS AND METHODS: As part of an ongoing prospective
      multicenter cohort study, we surveyed women with newly diagnosed early-stage
      breast cancer at age <= 40 years. The baseline survey included sociodemographic,
      medical, and treatment data as well as a modified Fertility Issues Survey,
      including fertility concern and preservation items. Univariable and multivariable
      modeling were used to investigate predictors of greater fertility concern.
      RESULTS: Among the first 620 eligible respondents included in this analysis,
      median age was 37 years (range, 17 to 40 years); 425 women (68%) discussed
      fertility issues with their physicians before starting therapy, and 319 (51%)
      were concerned about becoming infertile after treatment. Because of concerns
      about fertility, four women (1%) chose not to receive chemotherapy, 12 (2%) chose
      one chemotherapy regimen over another, six (1%) considered not receiving
      endocrine therapy, 19 (3%) decided not to receive endocrine therapy, and 71 (11%)
      considered receiving endocrine therapy for < 5 years; 65 (10%) used fertility
      preservation strategies. Greater concern about fertility was associated with
      younger age, nonwhite race, not having children, and receipt of chemotherapy.
      CONCLUSION: Many young women with newly diagnosed breast cancer have concerns
      about fertility, and for some, these substantially affect their treatment
      decisions. Only a minority of women currently pursue available fertility
      preservation strategies in this setting.

PMID- 24567429
TI  - Myelodysplastic syndrome successfully treated with adalimumab.

PMID- 24567430
TI  - Cost effectiveness of EML4-ALK fusion testing and first-line crizotinib treatment
      for patients with advanced ALK-positive non-small-cell lung cancer.
AB  - PURPOSE: ALK-targeted therapy with crizotinib offers significant improvement in
      clinical outcomes for the treatment of EML4-ALK fusion-positive non-small-cell
      lung cancer (NSCLC). We estimated the cost effectiveness of EML4-ALK fusion
      testing in combination with targeted first-line crizotinib treatment in Ontario.
      PATIENTS AND METHODS: A cost-effectiveness analysis was conducted using a Markov
      model from the Canadian Public health (Ontario) perspective and a lifetime
      horizon in patients with stage IV NSCLC with nonsquamous histology. Transition
      probabilities and mortality rates were calculated from the Ontario Cancer
      Registry and Cancer Care Ontario New Drug Funding Program (CCO NDFP). Costs were
      obtained from the Ontario Case Costing Initiative, CCO NDFP, University Health
      Network, and literature. RESULTS: Molecular testing with first-line targeted
      crizotinib treatment in the population with advanced nonsquamous NSCLC resulted
      in a gain of 0.011 quality-adjusted life-years (QALYs) compared with standard
      care. The incremental cost was Canadian $2,725 per patient, and the incremental
      cost-effectiveness ratio (ICER) was $255,970 per QALY gained. Among patients with
      known EML4-ALK-positive advanced NSCLC, first-line crizotinib therapy provided
      0.379 additional QALYs, cost an additional $95,043 compared with standard care,
      and produced an ICER of $250,632 per QALY gained. The major driver of cost
      effectiveness was drug price. CONCLUSION: EML4-ALK fusion testing in stage IV
      nonsquamous NSCLC with crizotinib treatment for ALK-positive patients is not cost
      effective in the setting of high drug costs and a low biomarker frequency in the
      population.

PMID- 24567431
TI  - Association between takotsubo cardiomyopathy and axitinib: case report and review
      of the literature.

PMID- 24567432
TI  - Cystic brain metastasis in non-small-cell lung cancer with ALK rearrangement.

PMID- 24567433
TI  - Recent clinical advances in lung cancer management.
AB  - Progress in lung cancer therapy has been slow but steady and has accelerated due
      to improvements in scientific basis for the disease and to technologic advances
      in diagnosis and therapy. The elusive goal of reduced mortality rates can be
      achieved in the next 50 years through continued interdisciplinary research
      efforts.

PMID- 24567434
TI  - Glioblastoma multiforme metastasis outside the CNS: three case reports and
      possible mechanisms of escape.

PMID- 24567436
TI  - BRAF(V600E) mutation in a histiocytic sarcoma arising from hairy cell leukemia.

PMID- 24567435
TI  - Impact of oophorectomy on cancer incidence and mortality in women with a BRCA1 or
      BRCA2 mutation.
AB  - PURPOSE: The purposes of this study were to estimate the reduction in risk of
      ovarian, fallopian tube, or peritoneal cancer in women with a BRCA1 or BRCA2
      mutation after oophorectomy, by age of oophorectomy; to estimate the impact of
      prophylactic oophorectomy on all-cause mortality; and to estimate 5-year survival
      associated with clinically detected ovarian, occult, and peritoneal cancers
      diagnosed in the cohort. PATIENTS AND METHODS: Women with a BRCA1 or BRCA2
      mutation were identified from an international registry; 5,783 women completed a
      baseline questionnaire and >= one follow-up questionnaires. Women were observed
      until either diagnosis of ovarian, fallopian tube, or peritoneal cancer, death,
      or date of most recent follow-up. Hazard ratios (HRs) for cancer incidence and
      all-cause mortality associated with oophorectomy were evaluated using time
      dependent survival analyses. RESULTS: After an average follow-up period of 5.6
      years, 186 women developed either ovarian (n = 132), fallopian (n = 22), or
      peritoneal (n = 32) cancer, of whom 68 have died. HR for ovarian, fallopian, or
      peritoneal cancer associated with bilateral oophorectomy was 0.20 (95% CI, 0.13
      to 0.30; P < .001). Among women who had no history of cancer at baseline, HR for
      all-cause mortality to age 70 years associated with an oophorectomy was 0.23 (95%
      CI, 0.13 to 0.39; P < .001). CONCLUSION: Preventive oophorectomy was associated
      with an 80% reduction in the risk of ovarian, fallopian tube, or peritoneal
      cancer in BRCA1 or BRCA2 carriers and a 77% reduction in all-cause mortality.

PMID- 24567437
TI  - Cost effectiveness of crizotinib for anaplastic lymphoma kinase-positive, non
      small-cell lung cancer: who is going to blink at the cost?

PMID- 24567438
TI  - Survival analysis with functional covariates for partial follow-up studies.
AB  - Predictive or prognostic analysis plays an increasingly important role in the era
      of personalized medicine to identify subsets of patients whom the treatment may
      benefit the most. Although various time-dependent covariate models are available,
      such models require that covariates be followed in the whole follow-up period.
      This article studies a new class of functional survival models where the
      covariates are only monitored in a time interval that is shorter than the whole
      follow-up period. This paper is motivated by the analysis of a longitudinal study
      on advanced myeloma patients who received stem cell transplants and T cell
      infusions after the transplants. The absolute lymphocyte cell counts were
      collected serially during hospitalization. Those patients are still followed up
      if they are alive after hospitalization, while their absolute lymphocyte cell
      counts cannot be measured after that. Another complication is that absolute
      lymphocyte cell counts are sparsely and irregularly measured. The conventional
      method using Cox model with time-varying covariates is not applicable because of
      the different lengths of observation periods. Analysis based on each single
      observation obviously underutilizes available information and, more seriously,
      may yield misleading results. This so-called partial follow-up study design
      represents increasingly common predictive modeling problem where we have serial
      multiple biomarkers up to a certain time point, which is shorter than the total
      length of follow-up. We therefore propose a solution to the partial follow-up
      design. The new method combines functional principal components analysis and
      survival analysis with selection of those functional covariates. It also has the
      advantage of handling sparse and irregularly measured longitudinal observations
      of covariates and measurement errors. Our analysis based on functional principal
      components reveals that it is the patterns of the trajectories of absolute
      lymphocyte cell counts, instead of the actual counts, that affect patient's
      disease-free survival time.

PMID- 24567439
TI  - A cautionary note on the use of attributable fractions in cohort studies.
AB  - The attributable fraction is a widely used measure to quantify the public health
      impact of an exposure on an outcome. It was originally proposed for binary
      outcomes, but attributable fraction estimators have also been proposed for time
      to-event outcomes. In this note, we consider an estimator which was proposed by
      Benichou (Stats Methods Med Res, 2001) and is supposed to estimate the cohort
      attributable fraction, i.e. the number of events that would have been prevented
      in the cohort during follow-up, if the exposure would hypothetically have been
      eliminated. We show that this estimator is only valid under certain assumptions,
      which are often likely to be violated in practice. We further argue that the
      cohort attributable fraction may not be of substantial scientific interest in the
      first place. We propose a potentially more relevant measure of attributable
      fraction in cohort studies; the baseline attributable fraction. We show how the
      baseline attributable fraction can be conveniently estimated in Cox proportional
      hazards models.

PMID- 24567440
TI  - Optimal scheduling of post-therapeutic follow-up of patients treated for cancer
      for early detection of relapses.
AB  - Post-therapeutic surveillance is one important component of cancer care. However,
      there still is no evidence-based strategies to schedule patients' follow-up
      examinations. Our approach is based on the modeling of the probability of the
      onset of relapse at an early asymptotic or preclinical stage and its transition
      to a clinical stage. For that we consider a multistate homogeneous Markov model,
      which includes the natural history of relapse. The model also handles separately
      the different types of possible relapses. The optimal schedule is provided by the
      calendar visit that maximizes a utility function. The methodology has been
      applied to laryngeal cancer. The different follow-up strategies revealed to be
      more efficient than those proposed by different scientific societies.

PMID- 24567441
TI  - Optimal selection of individuals for repeated covariate measurements in follow-up
      studies.
AB  - Repeated covariate measurements bring important information on the time-varying
      risk factors in long epidemiological follow-up studies. However, due to budget
      limitations, it may be possible to carry out the repeated measurements only for a
      subset of the cohort. We study cost-efficient alternatives for the simple random
      sampling in the selection of the individuals to be remeasured. The proposed
      selection criteria are based on forms of the D-optimality. The selection methods
      are compared with the simulation studies and illustrated with the data from the
      East-West study carried out in Finland from 1959 to 1999. The results indicate
      that cost savings can be achieved if the selection is focused on the individuals
      with high expected risk of the event and, on the other hand, on those with
      extreme covariate values in the previous measurements.

PMID- 24567443
TI  - Sociodemographic factors predicting mother's cervical screening and daughter's
      HPV vaccination uptake.
AB  - BACKGROUND: Achieving high human papillomavirus (HPV) vaccine coverage may reduce
      inequalities in cervical cancer prevention by mitigating the inequalities seen in
      the cervical screening programme. This paper assesses whether the same
      sociodemographic factors are associated with both cervical screening and HPV
      vaccination. METHODS: Girls' HPV vaccination records were linked by address to
      cervical screening records for their mothers in the North West of England. Index
      of Multiple Deprivation scores (2010) and census ethnicity data (2001) were used
      to investigate the association between deprivation and ethnic composition of area
      of residence with HPV vaccination and cervical screening uptake, along with
      potential differences between Primary Care Trusts (PCTs), which were responsible
      for vaccine delivery. RESULTS: Deprivation was not associated with routine (12-13
      year-olds) vaccination initiation, but girls living in the most deprived quintile
      were significantly less likely to complete the three vaccine doses (OR 0.75; 95%
      CI 0.63 to 0.88). Mother-daughter pairs failing to engage in either screening or
      vaccination were also more likely to live in deprived areas (routine vaccination
      OR for most deprived quintile: 2.35; 95% CI 2.00 to 2.77). There were differences
      between PCTs after controlling for demographic effects (OR 1.35; 95% CI 1.23 to
      1.52). CONCLUSIONS: Ensuring completion of the vaccine schedule is critical for
      organisations responsible for vaccine delivery in order to reduce cancer risk
      among girls living in deprived areas. There remains a small minority of mothers
      and daughters from disadvantaged backgrounds who do not participate in either
      cervical screening or HPV vaccination.

PMID- 24567442
TI  - Socioeconomic position across life and body composition in early old age:
      findings from a British birth cohort study.
AB  - BACKGROUND: Previous studies have reported associations between lower lifetime
      socioeconomic position (SEP) and higher body mass index in adulthood, but few
      have examined associations with direct measures of fat and lean mass which are
      likely to have independent roles in health and physical functioning. METHODS: We
      examined associations of SEP across life with dual-energy X-ray absorptiometry
      measures of fat and lean mass at 60-64 years using data from a total of 1558 men
      and women participating in the Medical Research Council (MRC) National Survey of
      Health and Development. We also examined whether associations of childhood SEP
      with fat and lean mass were explained by preadulthood weight gain (birth weight,
      0-7 and 7-20 years) and adult SEP. RESULTS: Lower SEP across life was associated
      with higher fat mass and higher android to gynoid fat mass ratio. For example,
      the mean difference in fat mass index comparing the lowest with the highest
      paternal occupational class at 4 years (slope index of inequality) was 1.04
      kg/m(1.2) in men (95% CI 0.09 to 1.99) and 2.61 in women (1.34 to 3.89),
      equivalent to a 8.6% and 16.1% difference, respectively. After adjustment for fat
      mass, lower SEP across life was associated with lower lean mass in women, while
      only contemporaneous household income was associated in men. Associations between
      childhood SEP and outcomes were partly explained by preadulthood weight gain and
      adult SEP. CONCLUSIONS: This study identified lifetime socioeconomic patterning
      of fat and lean mass in early old age. This is likely to have important
      implications and may partly explain socioeconomic inequalities in health and
      physical functioning.

PMID- 24567444
TI  - "Hidden" sexually transmitted infections among women in primary care health
      services, Amazonas, Brazil.
AB  - This study describes the prevalence of infection by Chlamydia trachomatis,
      Neisseria gonorrhoeae and Trichomonas vaginalis in a female population in
      Amazonas, Brazil. We collected cervical samples from 361 women examined at 10
      primary care health services in the city of Coari, Amazonas, Brazil. The women
      were interviewed about socio-economic data, clinical history and sexual
      behaviour. Pelvic examinations were performed and cervical specimens were
      collected for detection of pathogens by PCR. The prevalence of infection was:
      12.7% for Trichomonas vaginalis, 6.4% for Chlamydia trachomatis and 1.4% for
      Neisseria gonorrhoeae. There were no statistically significant associations
      between infections by any of the pathogens nor by any pathogen alone with any
      clinical variable, socio-demographic data or sexual behaviour. This study draws
      attention to the need for surveillance and possible need for screening for
      Chlamydia trachomatis, which often progresses asymptomatically. For the
      significant prevalence found, attention should also be given to asymptomatic
      infection by Trichomonas vaginalis, since this pathogen has recently been
      implicated as a risk factor for HIV infection.

PMID- 24567445
TI  - Abdominal and scrotal wall emphysema in a patient with severe ulcerative colitis.
AB  - Severe ulcerative colitis can be associated with bowel perforation. Bowel
      perforation rarely leads on to abdominal wall and scrotal wall emphysema. Bowel
      perforation in such cases can be spontaneous or iatrogenic (colonoscopy-related).
      We report a rare scenario where a patient presented with abdominal wall and
      scrotal emphysema after topical corticosteroid enema-induced traumatic rectal
      perforation. Topical corticosteroids were stopped immediately after
      identification of rectal perforation. The patient was managed conservatively with
      intravenous antibiotics. With this report we intend to sensitise clinicians and
      topical enema manufacturers regarding this rare complication. 

PMID- 24567446
TI  - Asymmetry in skeletal distribution of mouse hematopoietic stem cell clones and
      their equilibration by mobilizing cytokines.
AB  - Hematopoietic stem cells (HSCs) are able to migrate through the blood stream and
      engraft bone marrow (BM) niches. These features are key factors for successful
      stem cell transplantations that are used in cancer patients and in gene therapy
      protocols. It is unknown to what extent transplanted HSCs distribute throughout
      different anatomical niches in the BM and whether this changes with age. Here we
      determine the degree of hematopoietic migration at a clonal level by
      transplanting individual young and aged mouse HSCs labeled with barcoded viral
      vector, followed by assessing the skeletal distribution of hundreds of HSC
      clones. We detected highly skewed representation of individual clones in
      different bones at least 11 mo after transplantation. Importantly, a single
      challenge with the clinically relevant mobilizing agent granulocyte colony
      stimulating factor (G-CSF) caused rapid redistribution of HSCs across the
      skeletal compartments. Old and young HSC clones showed a similar level of
      migratory behavior. Clonal make-up of blood of secondary recipients recapitulates
      the barcode composition of HSCs in the bone of origin. These data demonstrate a
      previously unanticipated high skeletal disequilibrium of the clonal composition
      of HSC pool long-term after transplantation. Our findings have important
      implications for experimental and clinical and stem cell transplantation
      protocols. 

PMID- 24567449
TI  - Intracardiac echocardiography: evolving use in interventional cardiology.
AB  - Intracardiac echocardiography (ICE) uses a catheter-based steerable ultrasound
      probe that is passed into the right heart chambers to image intracardiac
      structures. The transducer can be variably positioned for optimal imaging: in the
      inferior vena cava to visualize the abdominal aorta; in the right atrium for the
      interatrial septum, aortic, mitral, and tricuspid valves, and pulmonary veins; or
      in the right ventricle for the left ventricular function, outflow tract, or
      pulmonary artery. Intracardiac echocardiography is primarily used for imaging
      during an invasive cardiac procedure using conscious sedation, when transthoracic
      image quality would likely be inadequate, and transesophageal imaging would
      require general anesthesia. Intracardiac echocardiography is generally well
      tolerated and provides adequate images and sufficient information for the
      procedure performed. In the cardiac catheterization laboratory, ICE is routinely
      used for patent foramen ovale, atrial septal defect, and ventricular septal
      defect closures, allowing adequate percutaneous placement of septal occluders. It
      is now being considered in the current era of transcatheter aortic valve
      implantation necessitating improved imaging approaches for accurate placement. It
      is also routinely used for trans-septal punctures during mitral valvuloplasty
      and, more recently, with the advent of left atrial appendage closure devices.
      This article provides a comprehensive review of the current technology for ICE
      and its growing applications in the realm of interventional cardiology. 

PMID- 24567447
TI  - Real-time immune cell interactions in target tissue during autoimmune-induced
      damage and graft tolerance.
AB  - Real-time imaging studies are reshaping immunological paradigms, but a visual
      framework is lacking for self-antigen-specific T cells at the effector phase in
      target tissues. To address this issue, we conducted intravital, longitudinal
      imaging analyses of cellular behavior in nonlymphoid target tissues to illustrate
      some key aspects of T cell biology. We used mouse models of T cell-mediated
      damage and protection of pancreatic islet grafts. Both CD4(+) and CD8(+) effector
      T (Teff) lymphocytes directly engaged target cells. Strikingly, juxtaposed beta
      cells lacking specific antigens were not subject to bystander destruction but
      grew substantially in days, likely by replication. In target tissue, Foxp3(+)
      regulatory T (Treg) cells persistently contacted Teff cells with or without
      involvement of CD11c(+) dendritic cells, an observation conciliating with the in
      vitro "trademark" of Treg function, contact-dependent suppression. This study
      illustrates tolerance induction by contact-based immune cell interaction in
      target tissues and highlights potentials of tissue regeneration under antigenic
      incognito in inflammatory settings.

PMID- 24567450
TI  - Prediction of maximal surface electromyographically based voluntary contractions
      of erector spinae muscles from sonographic measurements during isometric
      contractions.
AB  - OBJECTIVES: Currently, there are no studies combining electromyography (EMG) and
      sonography to estimate the absolute and relative strength values of erector
      spinae (ES) muscles in healthy individuals. The purpose of this study was to
      establish whether the maximum voluntary contraction (MVC) of the ES during
      isometric contractions could be predicted from the changes in surface EMG as well
      as in fiber pennation and thickness as measured by sonography. METHODS: Thirty
      healthy adults performed 3 isometric extensions at 45 degrees  from the vertical
      to calculate the MVC force. Contractions at 33% and 100% of the MVC force were
      then used during sonographic and EMG recordings. These measurements were used to
      observe the architecture and function of the muscles during contraction.
      Statistical analysis was performed using bivariate regression and regression
      equations. RESULTS: The slope for each regression equation was statistically
      significant (P < .001) with R(2) values of 0.837 and 0.986 for the right and left
      ES, respectively. The standard error estimate between the sonographic
      measurements and the regression-estimated pennation angles for the right and left
      ES were 0.10 and 0.02, respectively. CONCLUSIONS: Erector spinae muscle
      activation can be predicted from the changes in fiber pennation during isometric
      contractions at 33% and 100% of the MVC force. These findings could be essential
      for developing a regression equation that could estimate the level of muscle
      activation from changes in the muscle architecture.

PMID- 24567451
TI  - Distribution pattern of sonographically guided iliopsoas injections: cadaveric
      investigation using coned beam computed tomography.
AB  - OBJECTIVES: To investigate the distribution pattern of sonographically guided
      iliopsoas (IP) injections in an unembalmed cadaveric model. METHODS: A single
      experienced operator completed 10 sonographically guided IP injections in 5
      unembalmed cadaveric pelvic specimens (4 male and 1 female; ages 55-95 years;
      body mass indices, 15.5-27.5 kg/m(2)) using a previously described in-plane,
      lateral-to-medial approach short axis to the tendon. Each injection consisted of
      7 mL of a 20% dilution of contrast material injected between the IP tendon and
      the acetabular rim using a 22-gauge, 87.5-mm (31/2-in) needle. To facilitate
      interpretation of contrast patterns, 2 additional injections were performed on
      single hips: sonographically guided 14 mL contrast-latex IP injection and
      sonographically guided superficial IP "peritendinous" injection with 7 mL of
      contrast-latex. Immediately before and after each injection, fluoroscopic images
      were obtained with a fixed C-arm equipped with coned beam computed tomography.
      After each injection, radiographic images were evaluated by a board-certified,
      fellowship-trained musculoskeletal radiologist to determine injectate
      distribution. Specimens receiving contrast-latex injections were dissected 48
      hours after injection to determine the anatomic location of the injectate.
      RESULTS: Nine of 10 IP injections (90%) produced characteristic "U-shaped" flow
      patterns covering 50% to nearly 100% of the IP tendon circumference and
      resembling previously published IP bursograms. One injection was excluded because
      the majority of the latex was within the pectineus muscle, likely due to
      technical factors. Latex flowed an average of 5.3 cm (range, 0.3-7.9 cm) cephalad
      and 5.2 cm (range, 1.0-7.5 cm) caudad to the acetabular rim. The large-volume (14
      mL) IP injection produced a similar flow pattern to the 7 mL injections, whereas
      the superficial peritendinous injection produced a contrast pattern consistent
      with intramuscular flow. Subsequent dissection confirmed bursal flow for the 14
      mL injection, whereas the superficial peritendinous injection placed latex within
      the superficial portion of the IP muscle (ie, intramuscular). CONCLUSIONS:
      Sonographically guided IP injections using an in-plane, lateral-to-medial
      technique place injectate into the IP bursa between the IP tendon and the
      acetabular rim. Within the limits of this cadaveric investigation, this
      sonographically guided 7-mL IP "bursa" injection may provide a minimum of 50%
      circumferential IP tendon coverage and approximately 5 cm of cephalad and caudad
      flow. There does not appear to be a peritendinous space deep to the IP tendon at
      the acetabular rim that is both outside the bursa and amenable to sonographically
      guided injection. Injections into the superficial aspect of the IP using 7-mL
      volumes may not deliver injectate deep to the IP tendon and therefore may
      represent a fundamentally different injection.

PMID- 24567452
TI  - Simple and complex fibroadenomas: are there any distinguishing sonographic
      features?
AB  - OBJECTIVES: Complex fibroadenomas are fibroadenomas harboring 1 or more complex
      pathologic features: epithelial calcifications, apocrine metaplasia, sclerosing
      adenosis, and cysts larger than 3 mm. No sonographic features have been clearly
      defined for the distinction of simple fibroadenomas from complex ones, which are
      associated with an increased cancer risk. We aimed to evaluate the accuracy of
      sonographic features for the prediction of complexity in fibroadenomas. METHODS:
      A total of 252 fibroadenomas were found at consecutive percutaneous needle or
      excisional surgical biopsy. Sixty-three were excluded because their respective
      imaging examinations were not recorded on digital support and consequently were
      not available. According to histologic diagnoses, fibroadenomas (n = 189) were
      classified into simple (n = 159) and complex (n = 30). The size, number, and
      sonographic features were assessed, and their respective accuracy rates for
      prediction of complexity were analyzed. RESULTS: All patients were women. Complex
      fibroadenomas presented more frequently as solitary nodules (n = 21 [70%]) and
      were significantly larger than simple fibroadenomas (1.9 versus 1.3 cm; P =
      .009). Image predictors of complexity were an irregular shape (P< .001),
      noncircumscribed contours (indistinct, angular, microlobulated, or spiculated; P
      < .001), a complex echo structure (P < .001), the presence of microcalcifications
      (P = .002), and posterior acoustic enhancement (P < .001). By logistic
      multivariate regression, a complex echo structure (odds ratio [OR], 9.5; 95%
      confidence interval [CI], 2.8-32.3), noncircumscribed contours (OR, 3.7; 95% CI,
      1.1-12.8), and posterior acoustic enhancement (OR, 4.0; 95% CI, 1.1-14.6) were
      independent predictors of complexity. Receiver operating characteristic curve
      analysis showed that a complex echo structure was the most accurate sonographic
      finding for identification of complex fibroadenomas (area under the curve, 0.74).
      CONCLUSIONS: Certain sonographic features are associated with complex
      fibroadenomas and can help the radiologist decide which ones require biopsy.

PMID- 24567453
TI  - Nonmasslike lesions on breast sonography: comparison between benign and malignant
      lesions.
AB  - OBJECTIVES: To compare the imaging and clinical features of benign and malignant
      nonmasslike lesions in the breast. METHODS: During a 2-year period at a single
      institution, 186 nonmasslike lesions in 158 women were pathologically confirmed
      through surgery or sonographically guided biopsy. The sonographic patterns
      (mottled, geographic, and indistinct) and distributions (focal and regional) were
      compared between benign and malignant lesions. The presence of sonographically
      visible calcifications, amount of color Doppler signals, presence of positive
      findings on mammography, and presence of symptoms were also compared between the
      two groups. RESULTS: A total of 156 lesions (84%) were confirmed as benign and 30
      (16%) as malignant. On sonography, malignant nonmasslike lesions more frequently
      had mottled and geographic patterns and regional distribution than benign lesions
      (P < .0001). Malignant lesions also more frequently had sonographically visible
      calcifications (40% versus 0%; P < 0.0001) and a greater amount of color Doppler
      signals than benign lesions (P < .0001). On mammography, malignant lesions more
      frequently had densities and calcifications than benign lesions (30.4% versus
      7.1%; P = 0.0052; 73.9% versus 6.1%; P < .0001, respectively). Clinically,
      malignant lesions were more frequently palpable and accompanied by localized pain
      than benign lesions (50% versus 2.6%; P< .0001; 13.3% versus 0.6%; P = .0025).
      CONCLUSIONS: The imaging and clinical features of malignant nonmasslike lesions
      differed significantly from those of benign nonmasslike lesions.

PMID- 24567448
TI  - Co-targeting of convergent nucleotide biosynthetic pathways for leukemia
      eradication.
AB  - Pharmacological targeting of metabolic processes in cancer must overcome
      redundancy in biosynthetic pathways. Deoxycytidine (dC) triphosphate (dCTP) can
      be produced both by the de novo pathway (DNP) and by the nucleoside salvage
      pathway (NSP). However, the role of the NSP in dCTP production and DNA synthesis
      in cancer cells is currently not well understood. We show that acute
      lymphoblastic leukemia (ALL) cells avoid lethal replication stress after
      thymidine (dT)-induced inhibition of DNP dCTP synthesis by switching to NSP
      mediated dCTP production. The metabolic switch in dCTP production triggered by
      DNP inhibition is accompanied by NSP up-regulation and can be prevented using DI
      39, a new high-affinity small-molecule inhibitor of the NSP rate-limiting enzyme
      dC kinase (dCK). Positron emission tomography (PET) imaging was useful for
      following both the duration and degree of dCK inhibition by DI-39 treatment in
      vivo, thus providing a companion pharmacodynamic biomarker. Pharmacological co
      targeting of the DNP with dT and the NSP with DI-39 was efficacious against ALL
      models in mice, without detectable host toxicity. These findings advance our
      understanding of nucleotide metabolism in leukemic cells, and identify dCTP
      biosynthesis as a potential new therapeutic target for metabolic interventions in
      ALL and possibly other hematological malignancies.

PMID- 24567454
TI  - Reproducibility of renal volume measurement in adults using 3-dimensional
      sonography.
AB  - OBJECTIVES: The purpose of this study was to determine the interobserver
      reproducibility of renal volume measurement performed by 3-dimensional (3D)
      sonography. METHODS: We conducted an exploratory, quantitative, observational,
      and descriptive cross-sectional study. We calculated ranges, means, and standard
      deviations of the renal volumes obtained with 3D sonography by 2 different
      examiners from a sample of 30 patients. The interobserver reproducibility was
      assessed by calculating intraclass correlation coefficients (ICCs) and by
      construction of Bland-Altman plots. RESULTS: The ICC between the right 3D renal
      volumes obtained by examiners 1 and 2 was 0.8552 (95% confidence interval, 0.7153
      0.9292), showing excellent reproducibility (P < .0001). For the left 3D renal
      volumes obtained by examiners 1 and 2, the ICC was 0.6411 (95% confidence
      interval, 0.3652-0.8135), showing average to good reproducibility (P = .0001).
      The Bland-Altman plots showed mean differences +/- SD of -4.8% +/- 23.9% between
      the right renal volumes obtained by examiners 1 and 2 and -2.2% +/- 38% between
      the left renal volumes. The 95% limits of agreement between the right renal
      volumes obtained by examiners 1 and 2 were -28.7% to 19%, whereas those between
      the left renal volumes were -40.2% to 35.7%. CONCLUSIONS: Three-dimensional
      sonography showed good interobserver reproducibility, which was better for the
      right kidney. It appears necessary to establish standardized techniques for
      acquisition of sonographic renal volumes.

PMID- 24567455
TI  - Shear wave elastography for liver stiffness measurement in clinical sonographic
      examinations: evaluation of intraobserver reproducibility, technical failure, and
      unreliable stiffness measurements.
AB  - OBJECTIVES: The purpose of this study was to determine the optimal minimum number
      of liver stiffness measurements on shear wave elastography (SWE) and to evaluate
      the frequency of technical failures and unreliable stiffness measurements and the
      intraobserver reproducibility of SWE. METHODS: This retrospective study was
      approved by our Institutional Review Board, and informed consent was waived. From
      August 2011 to January 2013, 540 patients underwent abdominal sonography,
      including SWE. In 86 patients (group 1), the minimum number of examinations was
      determined by comparing the intraclass correlation coefficient (ICC) of subsets
      of the first 2 to 14 measurements with that from 15 measurements. In 454 patients
      (group 2), 2 SWE sessions were performed in the right lobe within 1 day.
      Technical failure was defined as when no or little signal was obtained in the
      elastogram during the first 5 acquisitions; unreliable SWE results were defined
      as when the interquartile range/median liver stiffness value exceeded 30%.
      Intraobserver reproducibility was assessed using ICCs and Bland-Altman plots.
      RESULTS: In group 1, the ICCs did not significantly increase after the first 6
      measurements. In group 2, there were technical failures and unreliable results in
      47 patients (10.35%) and 74 patients (16.29%), respectively. In 407 patients,
      after excluding technical failures, there was no significant difference in the
      median liver stiffness values between the 2 sessions (6.95 versus 6.86 kPa; P >
      .05). The overall intraobserver reproducibility was excellent (ICC, 0.95).
      CONCLUSIONS: In this study, the optimal minimum number of SWE measurements was 6,
      and SWE using 6 measurements showed excellent intraobserver reproducibility.

PMID- 24567457
TI  - Hospital-wide survey of bacterial contamination of point-of-care ultrasound
      probes and coupling gel.
AB  - OBJECTIVES: The purpose of this study was to determine the hospital-wide
      incidence of bacterial contamination of point-of-care (bedside) ultrasound probes
      and coupling gel at a single academic medical center to predict the risk of
      nosocomial spread of infection. METHODS: Bacterial cultures were performed on all
      point-of-care ultrasound probe surfaces and associated gel bottles in our
      institution (82 total probes in 9 separate departments). This process was
      repeated every 2 weeks for a total of 8 weeks; therefore, each probe was cultured
      4 times during the study period. RESULTS: Of the 320 probe cultures, 18 (5.6%),
      resulted in positive growth, all of which identified nonpathogenic organisms
      common to human skin flora and the environment. No methicillin-resistant
      Staphylococcus aureus or other notable pathogens were identified. No gel cultures
      resulted in bacterial growth. CONCLUSIONS: Bacterial contamination of point-of
      care ultrasound probes and coupling gel is low at this single academic medical
      center and involves nonpathogenic organisms only.

PMID- 24567458
TI  - Time to revisit the human chorionic gonadotropin discriminatory level in the
      management of pregnancy of unknown location.
AB  - OBJECTIVES: The purpose of this study was to review the management and outcomes
      of all patients with pregnancy of unknown location who had serum human chorionic
      gonadotropin (hCG) levels greater than 1000 mIU/mL in our institution and to
      determine the likelihood of a subsequent normal intrauterine pregnancy at
      different hCG discriminatory levels. METHODS: A retrospective review was
      performed on all women admitted with the diagnosis of pregnancy of unknown
      location and an hCG level greater than 1000 mIU/mL over a 5-year period (July
      2007 to June 2012). Patients were identified from a computerized hCG result
      database. The medical records, including sonographic findings, hCG levels, and
      outcomes, were reviewed. RESULTS: A total of 113 patients were identified. There
      were 23 viable intrauterine pregnancies (20.4%) and 22 visualized ectopic
      pregnancies (19.5%). The highest hCG level associated with a subsequent normal
      intrauterine pregnancy was 9083 mIU/mL in a patient with triplet pregnancy.
      Possible factors associated with nonvisualization of a normal intrauterine
      pregnancy included uterine fibroids, adenomyosis, endometrial polyps, and
      obesity. The negative laparoscopy rate was 48.8%. CONCLUSIONS: Viable
      intrauterine pregnancy is possible in patients with pregnancy of unknown location
      and hCG levels above the generally accepted discriminatory zone, strict adherence
      to which can potentially disrupt a normal pregnancy. We support the need for
      judicious use of the hCG discriminatory level in hemodynamically stable patients
      with pregnancy of unknown location, and the decision to intervene should not be
      based solely on a single hCG level.

PMID- 24567456
TI  - Differentiation of branch duct intraductal papillary mucinous neoplasms from
      serous cystadenomas of the pancreas using contrast-enhanced sonography.
AB  - OBJECTIVES: The purpose of this study was to determine whether contrast-enhanced
      sonography can improve the ability to differentiate branch duct intraductal
      mucinous neoplasms from serous cystadenomas of the pancreas compared to
      conventional (unenhanced) sonography alone. METHODS: Between March 2008 and May
      2012, there were 20 patients with branch duct intraductal mucinous neoplasms and
      25 with serous cystadenomas in our institute, for whom preoperative conventional
      and contrast-enhanced sonographic results were available. The final diagnosis was
      obtained by histopathology. Various conventional and contrast-enhanced
      sonographic characteristics were retrospectively evaluated by 2 radiologists in
      consensus. A receiver operating characteristic curve analysis was used to
      evaluate the diagnostic value of conventional and contrast-enhanced sonography
      for discriminating between the two entities. RESULTS: Three conventional
      sonographic characteristics (microcysts, cysts with internal echoes, and main
      pancreatic duct dilatation) and 2 contrast-enhanced sonographic characteristics
      (communication between the lesion and main pancreatic duct and enhancement of
      mural nodules) significantly improved the ability to differentiate branch duct
      intraductal mucinous neoplasms from serous cystadenomas. The area under the
      receiver operating characteristic curve increased from 0.691 with conventional
      sonography to 0.859 with combined contrast-enhanced and conventional
      ultrasonography (P = .043). CONCLUSIONS: In this series of patients, the addition
      of contrast-enhanced sonography to conventional sonography improved the ability
      to differentiate branch duct intraductal mucinous neoplasms from serous
      cystadenomas.

PMID- 24567459
TI  - Biometric sonographic findings of abnormally adherent trophoblastic implantations
      on cesarean delivery scars.
AB  - OBJECTIVES: The purpose of this study was to review first-trimester transvaginal
      sonograms of patients with cervicoisthmic implantations and prior cesarean
      deliveries to determine whether sonographic biometric measurements can
      distinguish between abnormally adherent trophoblastic implantations and normally
      implanted pregnancies. METHODS: Our database was reviewed from October 2006
      through December 2011 for patients with first-trimester sonographic diagnoses of
      cervicoisthmic implantations and previous cesarean deliveries. Biometric
      measurements of the smallest distance from the anterior trophoblastic border to
      the uterine serosa were performed on transvaginal sagittal images of the uterus.
      Outcomes were classified into 5 categories: cesarean scar pregnancy, placental
      invasion (accreta/increta/percreta), previa without invasion, spontaneous
      abortion, and delivered intrauterine pregnancy. Statistical methods included
      analysis of variance with the Tukey range test and Student t test. RESULTS: Of 77
      studies, outcome data were available for 56 patients. The mean gestational age
      was 8.8 weeks (minimum, 2.0 weeks; maximum, 14.9 weeks). The anterior
      trophoblastic border distances from the uterine serosa were significantly smaller
      in cesarean scar pregnancies (mean, 1.6 mm; SD, 0.6 mm) and placental invasion
      pregnancies (mean, 2.2 mm; SD, 1.0 mm) than the normally implanted groups (mean,
      7.9 mm, SD, 3.3 mm; P < .0001). CONCLUSIONS: Smaller trophoblastic border
      distances to the anterior uterine serosa are seen in abnormally adherent
      trophoblastic implantations, and these distances distinguish them from other
      pregnancy outcomes.

PMID- 24567460
TI  - Three-dimensional sonographic assessment of placental volume and vascularization
      in pregnancies complicated by hypertensive disorders.
AB  - OBJECTIVES: The purpose of this study was to evaluate the association between
      placental volumes, placental vascularity, and hypertensive disorders in
      pregnancy. METHODS: A prospective case-control study was conducted between April
      2011 and July 2012. Placental volumes and vascularity were evaluated by 3
      dimensional sonographic, 3-dimensional power Doppler histographic, and 2
      dimensional color Doppler studies. Pregnant women were classified as normotensive
      or hypertensive and stratified by the nature of their hypertensive disorders. The
      following variables were evaluated: observed-to-expected placental volume ratio,
      placental volume-to-estimated fetal weight ratio, placental vascular indices, and
      pulsatility indices of the right and left uterine and umbilical arteries.
      RESULTS: Sixty-six healthy pregnant women and 62 pregnant women with hypertensive
      disorders were evaluated (matched by maternal age, gestational age at sonography,
      and parity). Placental volumes were not reduced in pregnancy in women with
      hypertensive disorders (P > .05). Conversely, reduced placental vascularization
      indices (vascularization index and vascularization-flow index) were observed in
      pregnancies complicated by hypertensive disorders (P < .01; P < .01), especially
      in patients with superimposed preeclampsia (P = .04; P = .02). A weak correlation
      was observed between placental volumes, placental vascular indices, and Doppler
      studies of the uterine and umbilical arteries. CONCLUSIONS: Pregnancies
      complicated by hypertensive disorders are associated with reduced placental
      vascularity but not with reduced placental volumes. These findings are
      independent of changes in uterine artery Doppler studies. Future studies of the
      prediction of preeclampsia may focus on placental vascularity in combination with
      results of Doppler studies of the uterine arteries.

PMID- 24567461
TI  - Real-time ultrasound elastography for differentiation of benign and malignant
      thyroid nodules: a meta-analysis.
AB  - OBJECTIVES: The clinical challenge of managing thyroid nodules nowadays is to
      diagnose the minority of malignant disease. Real-time ultrasound elastography,
      which can measure tissue elasticity, is used as a complement to conventional
      sonography for improving the diagnosis of thyroid tumors. There are 2 common
      criteria for evaluating an elastogram: the elasticity score and strain ratio.
      This meta-analysis was performed to expand on a previous meta-analysis to assess
      the diagnostic power of ultrasound elastography in differentiating benign and
      malignant thyroid nodules for elasticity score and strain ratio assessment.
      METHODS: The MEDLINE, EMBASE, PubMed, and Cochrane Library databases up to
      January 31, 2013, were searched. The pooled sensitivity, specificity, and summary
      receiver operating characteristic curve were obtained from individual studies
      with a random-effects model. The extent and sources of heterogeneity were
      explored. RESULTS: A total of 5481 nodules in 4468 patients for elasticity score
      studies and 1063 nodules in 983 patients for strain ratio studies were analyzed.
      The overall mean sensitivity and specificity of ultrasound elastography for
      differentiation of thyroid nodules were 0.79 (95% confidence interval [CI], 0.77
      0.81) and 0.77 (95% CI, 0.76-0.79) for elasticity score assessment and 0.85 (95%
      CI, 0.81-0.89) and 0.80 (95% CI, 0.77-0.83) for strain ratio assessment,
      respectively. The areas under the curve for the elasticity score and strain ratio
      were 0.8941 and 0.9285. CONCLUSIONS: These results confirmed those obtained in
      the previous meta-analysis. Ultrasound elastography has high sensitivity and
      specificity for identification of thyroid nodules. It is a promising tool for
      reducing unnecessary fine-needle-aspiration biopsy.

PMID- 24567462
TI  - Relative proportions of stromal to cellular components of pleomorphic adenomas:
      determination with shear wave elastography.
AB  - OBJECTIVES: The purpose of this study was to evaluate whether the relative
      proportions of stromal to cellular components of pleomorphic adenomas have an
      effect on the shear elastic modulus determined by shear wave elastography (SWE).
      METHODS: This study was approved by the Ethics Committee of our institution and
      performed between September 2011 and December 2012. Thirty-five patients who
      underwent surgery for a parotid mass were included in the study. The maximum
      shear elastic modulus of the mass was measured by SWE. Pleomorphic adenomas were
      histopathologically subdivided into stroma-poor, intermediate-stroma, and stroma
      rich tumors based on the relative proportion of stromal to cellular components.
      RESULTS: The maximum shear elastic modulus values of the pleomorphic adenomas
      ranged from 12.6 to 291.9 kPa (mean +/- SD, 120.9 +/- 92.8 kPa). The Friedman
      test revealed a statistically significant relationship between the stromal amount
      and maximum shear elastic modulus (P < .001). Stroma-poor adenomas (mean, 32.3 +/
      27.7 kPa; range, 12.6-81.1 kPa) were softer on SWE than stroma-rich adenomas
      (mean, 174.1 +/- 48.4 kPa; range, 92.7-217.2 kPa; P = .009). No such significant
      difference was detected between stroma-poor and intermediate-stroma tumors (mean,
      146.3 +/- 106.1 kPa; range, 19.1-291.9 kPa; P = .062) or between intermediate
      stroma and stroma-rich tumors (P = .465). CONCLUSIONS: Shear wave elastography
      depicts pleomorphic adenomas with a variable appearance, which is due to the
      relative proportions of stromal to cellular contents in the tumors.

PMID- 24567463
TI  - Three-dimensional sonography in the evaluation of primary hyperparathyroidism.
AB  - Three-dimensional sonography is useful in the preoperative evaluation of patients
      with primary hyperparathyroidism. In this pictorial essay, we review the
      characteristic spectrum of grayscale and Doppler appearances of parathyroid
      glands on 2-dimensional sonography and demonstrate the additional benefits of 3
      dimensional scanning. 

PMID- 24567464
TI  - Three-dimensional endovaginal sonography of synthetic implanted materials in the
      female pelvic floor.
AB  - The objective of this pictorial essay is to emphasize the ability of 3
      dimensional endovaginal sonography to image synthetic implanted materials in the
      female pelvic floor. Implanted materials discussed in this pictorial essay
      include polypropylene vaginal mesh, polypropylene suburethral slings, and
      urethral bulking agents. Three-dimensional endovaginal sonography allows for more
      detailed imaging compared to computed tomography and magnetic resonance imaging
      of the female pelvic floor, in that each plane can be manipulated to show unique
      images of synthetic implanted materials. 

PMID- 24567465
TI  - Sister Mary Joseph nodule: a tip of an iceberg.
AB  - A Sister Mary Joseph nodule represents a cutaneous metastasis into the umbilicus.
      This clinical sign of intra-abdominal malignancy is frequently overlooked or
      misinterpreted by both patients and their physicians. We report 4 patients with a
      Sister Mary Joseph nodule. The umbilical metastases appeared sonographically as
      hypoechoic masses with irregular margins and small internal hyperechoic foci.
      Further evaluation revealed disseminated malignancy, and the umbilical nodule was
      just "a tip of an iceberg." 

PMID- 24567466
TI  - Aberrant drainage of the umbilical vein into the coronary sinus without ductus
      venosus agenesis.
AB  - We describe a case series of 4 fetuses with ectopic connections of the ductus
      venosus to the coronary sinus detected prospectively between August 2011 and
      February 2012 in 2 congenital cardiologic centers. An enlarged coronary sinus
      alerted the sonographer. Fetal echocardiography showed ectopic connection of the
      ductus venosus in an enlarged coronary sinus in all 4 cases. To our knowledge,
      this anatomic form of ectopic umbilical vein drainage has not previously been
      reported. The infants were doing well. This venous variant should be considered
      in cases of isolated coronary sinus dilatation after elimination of a left
      superior vena cava and a totally anomalous pulmonary vein connection. 

PMID- 24567467
TI  - Prenatal sonographic diagnosis of intrahepatic portosystemic shunts.
AB  - The incidence of fetal portosystemic anastomoses is unknown, and it is presumed
      that many cases remain undetected, as visualization of the hepatic vasculature is
      not part of the routine 20-week sonographic scan in pregnancy. However,
      portosystemic anastomoses are associated with fetal growth restriction due to a
      diminished oxygen supply to hepatocytes and, hence, downregulation of liver
      function. In these cases, uteroplacental perfusion might be normal. 

PMID- 24567468
TI  - Overlapping sutures: a new sign of a marked pressure effect in twin-twin
      transfusion syndrome.

PMID- 24567469
TI  - Anencephalic monocephalic conjoined twins detected by sonography.

PMID- 24567470
TI  - Single-photon imaging in complementary metal oxide semiconductor processes.
AB  - This paper describes the basics of single-photon counting in complementary metal
      oxide semiconductors, through single-photon avalanche diodes (SPADs), and the
      making of miniaturized pixels with photon-counting capability based on SPADs.
      Some applications, which may take advantage of SPAD image sensors, are outlined,
      such as fluorescence-based microscopy, three-dimensional time-of-flight imaging
      and biomedical imaging, to name just a few. The paper focuses on architectures
      that are best suited to those applications and the trade-offs they generate. In
      this context, architectures are described that efficiently collect the output of
      single pixels when designed in large arrays. Off-chip readout circuit
      requirements are described for a variety of applications in physics, medicine and
      the life sciences. Owing to the dynamic nature of SPADs, designs featuring a
      large number of SPADs require careful analysis of the target application for an
      optimal use of silicon real estate and of limited readout bandwidth. The paper
      also describes the main trade-offs involved in architecting such chips and the
      solutions adopted with focus on scalability and miniaturization. 

PMID- 24567471
TI  - Nanowire systems: technology and design.
AB  - Nanosystems are large-scale integrated systems exploiting nanoelectronic devices.
      In this study, we consider double independent gate, vertically stacked nanowire
      field effect transistors (FETs) with gate-all-around structures and typical
      diameter of 20 nm. These devices, which we have successfully fabricated and
      evaluated, control the ambipolar behaviour of the nanostructure by selectively
      enabling one type of carriers. These transistors work as switches with
      electrically programmable polarity and thus realize an exclusive or operation.
      The intrinsic higher expressive power of these FETs, when compared with standard
      complementary metal oxide semiconductor technology, enables us to realize more
      efficient logic gates, which we organize as tiles to realize nanowire systems by
      regular arrays. This article surveys both the technology for double independent
      gate FETs as well as physical and logic design tools to realize digital systems
      with this fabrication technology. 

PMID- 24567472
TI  - Plasmonics with two-dimensional conductors.
AB  - A wealth of effort in photonics has been dedicated to the study and engineering
      of surface plasmonic waves in the skin of three-dimensional bulk metals, owing
      largely to their trait of subwavelength confinement. Plasmonic waves in two
      dimensional conductors, such as semiconductor heterojunction and graphene,
      contrast the surface plasmonic waves on bulk metals, as the former emerge at
      gigahertz to terahertz and infrared frequencies well below the photonics regime
      and can exhibit far stronger subwavelength confinement. This review elucidates
      the machinery behind the unique behaviours of the two-dimensional plasmonic waves
      and discusses how they can be engineered to create ultra-subwavelength plasmonic
      circuits and metamaterials for infrared and gigahertz to terahertz integrated
      electronics. 

PMID- 24567473
TI  - Beyond CMOS: heterogeneous integration of III-V devices, RF MEMS and other
      dissimilar materials/devices with Si CMOS to create intelligent microsystems.
AB  - Advances in silicon technology continue to revolutionize micro-/nano-electronics.
      However, Si cannot do everything, and devices/components based on other materials
      systems are required. What is the best way to integrate these dissimilar
      materials and to enhance the capabilities of Si, thereby continuing the micro
      /nano-electronics revolution? In this paper, I review different approaches to
      heterogeneously integrate dissimilar materials with Si complementary metal oxide
      semiconductor (CMOS) technology. In particular, I summarize results on the
      successful integration of III-V electronic devices (InP heterojunction bipolar
      transistors (HBTs) and GaN high-electron-mobility transistors (HEMTs)) with Si
      CMOS on a common silicon-based wafer using an integration/fabrication process
      similar to a SiGe BiCMOS process (BiCMOS integrates bipolar junction and CMOS
      transistors). Our III-V BiCMOS process has been scaled to 200 mm diameter wafers
      for integration with scaled CMOS and used to fabricate radio-frequency (RF) and
      mixed signals circuits with on-chip digital control/calibration. I also show that
      RF microelectromechanical systems (MEMS) can be integrated onto this platform to
      create tunable or reconfigurable circuits. Thus, heterogeneous integration of III
      V devices, MEMS and other dissimilar materials with Si CMOS enables a new class
      of high-performance integrated circuits that enhance the capabilities of existing
      systems, enable new circuit architectures and facilitate the continued
      proliferation of low-cost micro-/nano-electronics for a wide range of
      applications. 

PMID- 24567474
TI  - High-throughput impedance spectroscopy biosensor array chip.
AB  - Impedance spectroscopy is a powerful tool for characterizing materials that
      exhibit a frequency dependent behaviour to an applied electric field. This paper
      introduces a fully integrated multi-channel impedance extraction circuit that can
      both generate AC stimulus signals over a broad frequency range and also measure
      and digitize the real and imaginary components of the impedance response. The
      circuit was fabricated in a 0.5 MUm complementary metal-oxide semiconductor.
      Tailored for cellular membrane interface characterization, the signal generator
      produces sinusoidal waves from 10 mHz to 10 kHz. To suit a variety of
      applications, the impedance extraction circuit provides a programmable current
      measurement range from 100 pA to 100 nA with a measured resolution of
      approximately 100 fA. Occupying only 0.045 mm(2) per measurement channel, the
      circuit is compact enough to include nearly 200 channels in a 3*3 mm(2) die area.

PMID- 24567475
TI  - Chemistry integrated circuit: chemical system on a complementary metal oxide
      semiconductor integrated circuit.
AB  - By integrating chemical reactions on a large-scale integration (LSI) chip, new
      types of device can be created. For biomedical applications, monolithically
      integrated sensor arrays for potentiometric, amperometric and impedimetric
      sensing of biomolecules have been developed. The potentiometric sensor array
      detects pH and redox reaction as a statistical distribution of fluctuations in
      time and space. For the amperometric sensor array, a microelectrode structure for
      measuring multiple currents at high speed has been proposed. The impedimetric
      sensor array is designed to measure impedance up to 10 MHz. The multimodal sensor
      array will enable synthetic analysis and make it possible to standardize
      biosensor chips. Another approach is to create new functional devices by
      integrating molecular systems with LSI chips, for example image sensors that
      incorporate biological materials with a sensor array. The quantum yield of the
      photoelectric conversion of photosynthesis is 100%, which is extremely difficult
      to achieve by artificial means. In a recently developed process, a molecular wire
      is plugged directly into a biological photosynthetic system to efficiently
      conduct electrons to a gold electrode. A single photon can be detected at room
      temperature using such a system combined with a molecular single-electron
      transistor. 

PMID- 24567477
TI  - Terahertz real-time imaging uncooled array based on antenna- and cavity-coupled
      bolometers.
AB  - The development of terahertz (THz) applications is slowed down by the
      availability of affordable, easy-to-use and highly sensitive detectors. CEA-Leti
      took up this challenge by tailoring the mature infrared (IR) bolometer technology
      for optimized THz sensing. The key feature of these detectors relies on the
      separation between electromagnetic absorption and the thermometer. For each
      pixel, specific structures of antennas and a resonant quarter-wavelength cavity
      couple efficiently the THz radiation on a broadband range, while a central
      silicon microbridge bolometer resistance is read out by a complementary metal
      oxide semiconductor circuit. 320*240 pixel arrays have been designed and
      manufactured: a better than 30 pW power direct detection threshold per pixel has
      been demonstrated in the 2-4 THz range. Such performance is expected on the whole
      THz range by proper tailoring of the antennas while keeping the technological
      stack largely unchanged. This paper gives an overview of the developed bolometer
      based technology. First, it describes the technology and reports the latest
      performance characterizations. Then imaging demonstrations are presented, such as
      real-time reflectance imaging of a large surface of hidden objects and THz time
      domain spectroscopy beam two-dimensional profiling. Finally, perspectives of
      camera integration for scientific and industrial applications are discussed. 

PMID- 24567476
TI  - Analog synthetic biology.
AB  - We analyse the pros and cons of analog versus digital computation in living
      cells. Our analysis is based on fundamental laws of noise in gene and protein
      expression, which set limits on the energy, time, space, molecular count and part
      count resources needed to compute at a given level of precision. We conclude that
      analog computation is significantly more efficient in its use of resources than
      deterministic digital computation even at relatively high levels of precision in
      the cell. Based on this analysis, we conclude that synthetic biology must use
      analog, collective analog, probabilistic and hybrid analog-digital computational
      approaches; otherwise, even relatively simple synthetic computations in cells
      such as addition will exceed energy and molecular-count budgets. We present
      schematics for efficiently representing analog DNA-protein computation in cells.
      Analog electronic flow in subthreshold transistors and analog molecular flux in
      chemical reactions obey Boltzmann exponential laws of thermodynamics and are
      described by astoundingly similar logarithmic electrochemical potentials.
      Therefore, cytomorphic circuits can help to map circuit designs between
      electronic and biochemical domains. We review recent work that uses positive
      feedback linearization circuits to architect wide-dynamic-range logarithmic
      analog computation in Escherichia coli using three transcription factors, nearly
      two orders of magnitude more efficient in parts than prior digital
      implementations. 

PMID- 24567478
TI  - A new era of semiconductor genetics using ion-sensitive field-effect transistors:
      the gene-sensitive integrated cell.
AB  - Semiconductor genetics is now disrupting the field of healthcare owing to the
      rapid parallelization and scaling of DNA sensing using ion-sensitive field-effect
      transistors (ISFETs) fabricated using commercial complementary metal -oxide
      semiconductor technology. The enabling concept of DNA reaction monitoring
      introduced by Toumazou has made this a reality and we are now seeing relentless
      scaling with Moore's law ultimately achieving the $100 genome. In this paper, we
      present the next evolution of this technology through the creation of the gene
      sensitive integrated cell (GSIC) for label-free real-time analysis based on
      ISFETs. This device is derived from the traditional metal-oxide semiconductor
      field-effect transistor (MOSFET) and has electrical performance identical to that
      of a MOSFET in a standard semiconductor process, yet is capable of incorporating
      DNA reaction chemistries for applications in single nucleotide polymorphism
      microarrays and DNA sequencing. Just as application-specific integrated circuits,
      which are developed in much the same way, have shaped our consumer electronics
      industry and modern communications and memory technology, so, too, do GSICs based
      on a single underlying technology principle have the capacity to transform the
      life science and healthcare industries. 

PMID- 24567480
TI  - Beyond Moore's law.

PMID- 24567479
TI  - Silicon-based silicon-germanium-tin heterostructure photonics.
AB  - The wavelength range that extends from 1550 to 5000 nm is a new regime of
      operation for Si-based photonic and opto-electronic integrated circuits. To
      actualize the new chips, heterostructure active devices employing the ternary
      SiGeSn alloy are proposed in this paper. Foundry-based monolithic integration is
      described. Opportunities and challenges abound in creating laser diodes, optical
      amplifiers, light-emitting diodes, photodetectors, modulators, switches and a
      host of high-performance passive infrared waveguided components. 

PMID- 24567492
TI  - Love is a battlefield: programmed cell death during fertilization.
AB  - Plant development and growth is sustained by the constant generation of
      tremendous amounts of cells, which become integrated into various types of
      tissues and organs. What is all too often overlooked is that this thriving life
      also requires the targeted degeneration of selected cells, which undergo cell
      death according to genetically encoded programmes or environmental stimuli. The
      side-by-side existence of generation and demise is particularly evident in the
      haploid phase of the flowering plants cycle. Here, the lifespan of terminally
      differentiated accessory cells contrasts with that of germ cells, which by
      definition live on to form the next generation. In fact, with research in recent
      years it is becoming increasingly clear that the gametophytes of flowering plants
      constitute an attractive and powerful system for investigating the molecular
      mechanisms underlying selective cell death. 

PMID- 24567493
TI  - Synthetic biology as it relates to CAM photosynthesis: challenges and
      opportunities.
AB  - To meet future food and energy security needs, which are amplified by increasing
      population growth and reduced natural resource availability, metabolic
      engineering efforts have moved from manipulating single genes/proteins to
      introducing multiple genes and novel pathways to improve photosynthetic
      efficiency in a more comprehensive manner. Biochemical carbon-concentrating
      mechanisms such as crassulacean acid metabolism (CAM), which improves
      photosynthetic, water-use, and possibly nutrient-use efficiency, represent a
      strategic target for synthetic biology to engineer more productive C3 crops for a
      warmer and drier world. One key challenge for introducing multigene traits like
      CAM onto a background of C3 photosynthesis is to gain a better understanding of
      the dynamic spatial and temporal regulatory events that underpin photosynthetic
      metabolism. With the aid of systems and computational biology, vast amounts of
      experimental data encompassing transcriptomics, proteomics, and metabolomics can
      be related in a network to create dynamic models. Such models can undergo
      simulations to discover key regulatory elements in metabolism and suggest
      strategic substitution or augmentation by synthetic components to improve
      photosynthetic performance and water-use efficiency in C3 crops. Another key
      challenge in the application of synthetic biology to photosynthesis research is
      to develop efficient systems for multigene assembly and stacking. Here, we review
      recent progress in computational modelling as applied to plant photosynthesis,
      with attention to the requirements for CAM, and recent advances in synthetic
      biology tool development. Lastly, we discuss possible options for multigene
      pathway construction in plants with an emphasis on CAM-into-C3 engineering. 

PMID- 24567496
TI  - Balancing act: matching growth with environment by the TOR signalling pathway.
AB  - One of the most fundamental aspects of growth in plants is its plasticity in
      relation to fluctuating environmental conditions. Growth of meristematic cells
      relies predominantly on protein synthesis, one of the most energy-consuming
      activities in cells, and thus is tightly regulated in accordance with the
      available nutrient and energy supplies. The Target of Rapamycin (TOR) signalling
      pathway takes a central position in this regulation. The core of the TOR
      signalling pathway is conserved throughout evolution, and can be traced back to
      the last eukaryotic common ancestor. In plants, a single complex constitutes the
      TOR signalling pathway. Manipulating the components of the TOR complex in
      Arabidopsis highlighted its common role as a major regulator of protein synthesis
      and metabolism, that is also involved in other biological functions such as cell
      wall integrity, regulation of cell proliferation, and cell size. TOR, as an
      integral part of the auxin signalling pathway, connects hormonal and nutrient
      pathways. Downstream of TOR, S6 kinase and the ribosomal S6 protein have been
      shown to mediate several of these responses, although there is evidence of other
      complex non-linear TOR signalling pathway structures. 

PMID- 24567495
TI  - Members of the barley NAC transcription factor gene family show differential co
      regulation with senescence-associated genes during senescence of flag leaves.
AB  - The senescence process of plants is important for the completion of their life
      cycle, particularly for crop plants, it is essential for efficient nutrient
      remobilization during seed filling. It is a highly regulated process, and in
      order to address the regulatory aspect, the role of genes in the NAC
      transcription factor family during senescence of barley flag leaves was studied.
      Several members of the NAC transcription factor gene family were up-regulated
      during senescence in a microarray experiment, together with a large range of
      senescence-associated genes, reflecting the coordinated activation of degradation
      processes in senescing barley leaf tissues. This picture was confirmed in a
      detailed quantitative reverse transcription-PCR (qRT-PCR) experiment, which also
      showed distinct gene expression patterns for different members of the NAC gene
      family, suggesting a group of ~15 out of the 47 studied NAC genes to be important
      for signalling processes and for the execution of degradation processes during
      leaf senescence in barley. Seven models for DNA-binding motifs for NAC
      transcription factors were designed based on published motifs, and available
      promoter sequences of barley genes were screened for the motifs. Genes up
      regulated during senescence showed a significant over-representation of the
      motifs, suggesting regulation by the NAC transcription factors. Furthermore, co
      regulation studies showed that genes possessing the motifs in the promoter in
      general were highly co-expressed with members of the NAC gene family. In
      conclusion, a list of up to 15 NAC genes from barley that are strong candidates
      for being regulatory factors of importance for senescence and biotic stress
      related traits affecting the productivity of cereal crop plants has been
      generated. Furthermore, a list of 71 senescence-associated genes that are
      potential target genes for these NAC transcription factors is presented. 

PMID- 24567494
TI  - Sixteen cytosolic glutamine synthetase genes identified in the Brassica napus L.
      genome are differentially regulated depending on nitrogen regimes and leaf
      senescence.
AB  - A total of 16 BnaGLN1 genes coding for cytosolic glutamine synthetase isoforms
      (EC 6.3.1.2.) were found in the Brassica napus genome. The total number of
      BnaGLN1 genes, their phylogenetic relationships, and genetic locations are in
      agreement with the evolutionary history of Brassica species. Two BnaGLN1.1, two
      BnaGLN1.2, six BnaGLN1.3, four BnaGLN1.4, and two BnaGLN1.5 genes were found and
      named according to the standardized nomenclature for the Brassica genus. Gene
      expression showed conserved responses to nitrogen availability and leaf
      senescence among the Brassiceae tribe. The BnaGLN1.1 and BnaGLN1.4 families are
      overexpressed during leaf senescence and in response to nitrogen limitation. The
      BnaGLN1.2 family is up-regulated under high nitrogen regimes. The members of the
      BnaGLN1.3 family are not affected by nitrogen availability and are more expressed
      in stems than in leaves. Expression of the two BnaGLN1.5 genes is almost
      undetectable in vegetative tissues. Regulations arising from plant interactions
      with their environment (such as nitrogen resources), final architecture, and
      therefore sink-source relations in planta, seem to be globally conserved between
      Arabidopsis and B. napus. Similarities of the coding sequence (CDS) and protein
      sequences, expression profiles, response to nitrogen availability, and ageing
      suggest that the roles of the different GLN1 families have been conserved among
      the Brassiceae tribe. These findings are encouraging the transfer of knowledge
      from the Arabidopsis model plant to the B. napus crop plant. They are of special
      interest when considering the role of glutamine synthetase in crop yield and
      grain quality in maize and wheat. 

PMID- 24567497
TI  - Paediatric CT optimisation utilising Catphan(r) 600 and age-specific
      anthropomorphic phantoms.
AB  - The purpose of the study is to perform phantom-based optimisation of paediatric
      computed tomography (CT) protocols and quantify the impact upon radiation dose
      and image noise levels. The study involved three Portuguese paediatric centres.
      Currently employed scanning protocols for head and chest examinations and
      combinations of exposure parameters were applied to a Catphan((r))600 phantom to
      review the CT dose impact. Contrast-noise ratio (CNR) was quantified using Radia
      Diagnostic((r)) tool. Imaging parameters, returning similar CNRs (<1) and dose
      savings were applied to three paediatric anthropomorphic phantoms. OsiriX
      software based on standard deviation pixel values facilitated image noise
      analysis. Currently employed protocols and age categorisation varied between
      centres. Manipulation of exposure parameters facilitated mean dose reductions of
      33 and 28 % for paediatric head and chest CT examinations, respectively. The
      majority of the optimised CT examinations resulted in image noise similar to
      currently employed protocols. Dose reductions of up to 33 % were achieved with
      image quality maintained. 

PMID- 24567498
TI  - Neutron dose rate at the SwissFEL injector test facility: first measurements.
AB  - At the Paul Scherrer Institute, the new SwissFEL Free Electron Laser facility is
      currently in the design phase. It is foreseen to accelerate electrons up to a
      maximum energy of 7 GeV with a pulsed time structure. An injector test facility
      is operated at a maximum energy of 300 MeV and serves as the principal test and
      demonstration plant for the SwissFEL project. Secondary radiation is created in
      unavoidable interactions of the primary beam with beamline components. The
      resulting ambient dose-equivalent rate due to neutrons was measured along the
      beamline with different commercially available survey instruments. The present
      study compares the readings of these neutron detectors (one of them is
      specifically designed for measurements in pulsed fields). The experiments were
      carried out in both, a normal and a diagnostic mode of operation of the injector.

PMID- 24567499
TI  - A survey of the urban radiofrequency (RF) environment.
AB  - In 1980, Tell and Mantiply published a study of radiofrequency (RF) fields
      measured across 15 major metropolitan areas in the USA. They required a van fully
      equipped with instrumentation and computing capability for their measurements.
      This study aimed to assess whether and how hand-held instrumentation available
      today would facilitate and enhance the efficiency of large-scale surveys of
      ambient RF fields. In addition, the data would provide a suggestion as to how the
      profile of ambient RF fields has changed with respect to frequency content and
      magnitude. Not unexpectedly, the relative power densities were orders of
      magnitude lower than the Federal Communications Commission's (FCC) maximum
      permissible exposure (MPE) for the general public, with a maximum time-averaged
      value across the VHF-FM-UHF-cellular bands of 0.12 % of the MPE (AM's
      contribution was negligible). In both the 1980 and the present study, the power
      density in the FM band was a major contributor to overall power density, but over
      time, power densities in the VHF and UHF band decreased and increased,
      respectively. From the perspective of absolute power density, the wideband values
      in the 1980 study, this study and any number of assessments conducted in European
      nations are not generally different from one another. 

PMID- 24567500
TI  - Design and manufacturing of anthropomorphic thyroid-neck phantom for use in
      nuclear medicine centres in Chile.
AB  - Anthropomorphic phantoms are used in nuclear medicine for imaging quality
      control, calibration of gamma spectrometry system for the study of internal
      contamination with radionuclides and for internal dosimetric studies. These are
      constructed of materials that have radiation attenuation coefficients similar to
      those of the different organs and tissues of the human body. The material usually
      used for the manufacture of phantoms is polymethyl methacrylate. Other materials
      used for this purpose are polyethylene, polystyrene and epoxy resin. This project
      presents the design and manufacture of an anthropomorphic thyroid-neck phantom
      that includes the cervical spine, trachea and oesophagus, using a polyester resin
      (rho = 1.1 g cm(-3)). Its linear and mass attenuation coefficients were
      experimentally determined and simulated by means of XCOM software, finding that
      this material reproduces the soft tissue ICRU-44 in a range of energies between
      80 keV and 11 MeV, with less than a 5 % difference. 

PMID- 24567501
TI  - Reference map and comparative proteomic analysis of Neisseria gonorrhoeae
      displaying high resistance against spectinomycin.
AB  - A proteome reference map of Neisseria gonorrhoeae was successfully established
      using two-dimensional gel electrophoresis in conjunction with matrix-assisted
      laser desorption ionization-time of flight mass spectrometry. This map was
      further applied to compare protein expression profiles of high-level
      spectinomycin-resistant (clinical isolate) and -susceptible (reference strain) N.
      gonorrhoeae following treatment with subminimal inhibitory concentrations
      (subMICs) of spectinomycin. Approximately 200 protein spots were visualized by
      Coomassie brilliant blue G-250 staining and 66 spots representing 58 unique
      proteins were subsequently identified. Most of the identified proteins were
      analysed as cytoplasmic proteins and belonged to the class of energy metabolism.
      Comparative proteomic analysis of whole protein expression of susceptible and
      resistant gonococci showed up to 96% similarity while eight proteins were found
      to be differentially expressed in the resistant strain. In the presence of
      subMICs of spectinomycin, it was found that 50S ribosomal protein L7/L12, an
      essential component for ribosomal translocation, was upregulated in both strains,
      ranging from 1.5- to 3.5-fold, suggesting compensatory mechanisms of N.
      gonorrhoeae in response to antibiotic that inhibits protein synthesis. Moreover,
      the differential expression of proteins involved in energy metabolism, amino acid
      biosynthesis, and the cell envelope was noticeably detected, indicating
      significant cellular responses and adaptation against antibiotic stress. Such
      knowledge provides valuable data, not only fundamental proteomic data, but also
      knowledge of the mode of action of antibiotic and secondary target proteins
      implicated in adaptation and compensatory mechanisms.

PMID- 24567503
TI  - Two cases of arteriovenous fistula formation between the external iliac vessels
      following endovenous laser therapy.
AB  - Minimally invasive treatment of varicose veins is becoming increasingly popular
      with both patients and physicians. Endovenous laser therapy has been shown to be
      safe and effective but the rare complication of iatrogenic creation of
      arteriovenous fistulas has been described. One case of fistulation between the
      external iliac artery and vein has been published. We report two further cases
      and describe their management. 

PMID- 24567504
TI  - Chronic complete thrombosis of abdominal aortic aneurysm: an unusual presentation
      of an unusual complication.
AB  - Although mural thrombosis frequently accompanies aneurysmal disease, complete
      thrombosis is distinctly unusual complication of abdominal aortic aneurysm (AAA).
      A case study of a patient with chronic, asymptomatic complete thrombosis of a
      large juxtarenal AAA is presented along with a literature review and discussion
      of the potential secondary complications, mandating aggressive management of this
      condition. A 67-year-old man with multiple atherogenic risk factors and
      unattended complaints consistent with a recent episode of a transient right
      hemispheric ischemic attack was referred to our clinic with a diagnosis of a
      thrombosed AAA established by computed tomography. Duplex ultrasonography and
      aortography confirmed the referral diagnosis and also revealed near occlusion of
      the left internal carotid artery. The patient underwent a two-stage surgery, with
      preliminary left-sided carotid endarterectomy followed three days later by an
      aneurysmectomy and aortobifemoral reconstruction. He had an uncomplicated
      recovery and was discharged home on postoperative day 7, remaining asymptomatic
      at the 42-month follow-up. Complete thrombosis is an uncommon presentation of AAA
      and may be clinically silent. It is frequently associated with other
      manifestations of generalized atherosclerosis. Radical open repair yields durable
      result and is the preferred treatment modality. 

PMID- 24567506
TI  - Of ATP receptors, opioid receptors, and AKAP regulation of calcium channels.

PMID- 24567502
TI  - Genetic relationships between schizophrenia, bipolar disorder, and
      schizoaffective disorder.
AB  - There is substantial evidence for partial overlap of genetic influences on
      schizophrenia and bipolar disorder, with family, twin, and adoption studies
      showing a genetic correlation between the disorders of around 0.6. Results of
      genome-wide association studies are consistent with commonly occurring genetic
      risk variants, contributing to both the shared and nonshared aspects, while
      studies of large, rare chromosomal structural variants, particularly copy number
      variants, show a stronger influence on schizophrenia than bipolar disorder to
      date. Schizoaffective disorder has been less investigated but shows substantial
      familial overlap with both schizophrenia and bipolar disorder. A twin analysis is
      consistent with genetic influences on schizoaffective episodes being entirely
      shared with genetic influences on schizophrenic and manic episodes, while
      association studies suggest the possibility of some relatively specific genetic
      influences on broadly defined schizoaffective disorder, bipolar subtype. Further
      insights into genetic relationships between these disorders are expected as
      studies continue to increase in sample size and in technical and analytical
      sophistication, information on phenotypes beyond clinical diagnoses are
      increasingly incorporated, and approaches such as next-generation sequencing
      identify additional types of genetic risk variant. 

PMID- 24567507
TI  - Differential regulation of CaV1.2 channels by cAMP-dependent protein kinase bound
      to A-kinase anchoring proteins 15 and 79/150.
AB  - The CaV1.1 and CaV1.2 voltage-gated calcium channels initiate excitation
      contraction coupling in skeletal and cardiac myocytes, excitation-transcription
      coupling in neurons, and many other cellular processes. Up-regulation of their
      activity by the beta-adrenergic-PKA signaling pathway increases these
      physiological responses. PKA up-regulation of CaV1.2 activity can be
      reconstituted in a transfected cell system expressing CaV1.2Delta1800 truncated
      at the in vivo proteolytic processing site, the distal C-terminal domain (DCT;
      CaV1.2[1801-2122]), the auxiliary alpha2delta and beta subunits of CaV1.2
      channels, and A-kinase anchoring protein-15 (AKAP15), which binds to a site in
      the DCT. AKAP79/150 binds to the same site in the DCT as AKAP15. Here we report
      that AKAP79 is ineffective in supporting up-regulation of CaV1.2 channel activity
      by PKA, even though it binds to the same site in the DCT and inhibits the up
      regulation of CaV1.2 channel activity supported by AKAP15. Mutation of the
      calcineurin-binding site in AKAP79 (AKAP79DeltaPIX) allows it to support PKA
      dependent up-regulation of CaV1.2 channel activity, suggesting that calcineurin
      bound to AKAP79 rapidly dephosphorylates CaV1.2 channels, thereby preventing
      their regulation by PKA. Both AKAP15 and AKAP79DeltaPIX exert their regulatory
      effects on CaV1.2 channels in transfected cells by interaction with the modified
      leucine zipper motif in the DCT. Our results introduce an unexpected mode of
      differential regulation by AKAPs, in which binding of different AKAPs at a single
      site can competitively confer differential regulatory effects on the target
      protein by their association with different signaling proteins.

PMID- 24567508
TI  - Divergence of Ca(2+) selectivity and equilibrium Ca(2+) blockade in a Ca(2+)
      release-activated Ca(2+) channel.
AB  - Prevailing models postulate that high Ca(2+) selectivity of Ca(2+) release
      activated Ca(2+) (CRAC) channels arises from tight Ca(2+) binding to a high
      affinity site within the pore, thereby blocking monovalent ion flux. Here, we
      examined the contribution of high affinity Ca(2+) binding for Ca(2+) selectivity
      in recombinant Orai3 channels, which function as highly Ca(2+)-selective channels
      when gated by the endoplasmic reticulum Ca(2+) sensor STIM1 or as poorly Ca(2+)
      selective channels when activated by the small molecule 2-aminoethoxydiphenyl
      borate (2-APB). Extracellular Ca(2+) blocked Na(+) currents in both gating modes
      with a similar inhibition constant (Ki; ~25 uM). Thus, equilibrium binding as set
      by the Ki of Ca(2+) blockade cannot explain the differing Ca(2+) selectivity of
      the two gating modes. Unlike STIM1-gated channels, Ca(2+) blockade in 2-APB-gated
      channels depended on the extracellular Na(+) concentration and exhibited an
      anomalously steep voltage dependence, consistent with enhanced Na(+) pore
      occupancy. Moreover, the second-order rate constants of Ca(2+) blockade were
      eightfold faster in 2-APB-gated channels than in STIM1-gated channels. A four
      barrier, three-binding site Eyring model indicated that lowering the entry and
      exit energy barriers for Ca(2+) and Na(+) to simulate the faster rate constants
      of 2-APB-gated channels qualitatively reproduces their low Ca(2+) selectivity,
      suggesting that ion entry and exit rates strongly affect Ca(2+) selectivity.
      Noise analysis indicated that the unitary Na(+) conductance of 2-APB-gated
      channels is fourfold larger than that of STIM1-gated channels, but both modes of
      gating show a high open probability (Po; ~0.7). The increase in current noise
      during channel activation was consistent with stepwise recruitment of closed
      channels to a high Po state in both cases, suggesting that the underlying gating
      mechanisms are operationally similar in the two gating modes. These results
      suggest that both high affinity Ca(2+) binding and kinetic factors contribute to
      high Ca(2+) selectivity in CRAC channels.

PMID- 24567509
TI  - Complex role of STIM1 in the activation of store-independent Orai1/3 channels.
AB  - Orai proteins contribute to Ca(2+) entry into cells through both store-dependent,
      Ca(2+) release-activated Ca(2+) (CRAC) channels (Orai1) and store-independent,
      arachidonic acid (AA)-regulated Ca(2+) (ARC) and leukotriene C4 (LTC4)-regulated
      Ca(2+) (LRC) channels (Orai1/3 heteromultimers). Although activated by
      fundamentally different mechanisms, CRAC channels, like ARC and LRC channels,
      require stromal interacting molecule 1 (STIM1). The role of endoplasmic reticulum
      resident STIM1 (ER-STIM1) in CRAC channel activation is widely accepted. Although
      ER-STIM1 is necessary and sufficient for LRC channel activation in vascular
      smooth muscle cells (VSMCs), the minor pool of STIM1 located at the plasma
      membrane (PM-STIM1) is necessary for ARC channel activation in HEK293 cells. To
      determine whether ARC and LRC conductances are mediated by the same or different
      populations of STIM1, Orai1, and Orai3 proteins, we used whole-cell and
      perforated patch-clamp recording to compare AA- and LTC4-activated currents in
      VSMCs and HEK293 cells. We found that both cell types show indistinguishable
      nonadditive LTC4- and AA-activated currents that require both Orai1 and Orai3,
      suggesting that both conductances are mediated by the same channel. Experiments
      using a nonmetabolizable form of AA or an inhibitor of 5-lipooxygenase suggested
      that ARC and LRC currents in both cell types could be activated by either LTC4 or
      AA, with LTC4 being more potent. Although PM-STIM1 was required for current
      activation by LTC4 and AA under whole-cell patch-clamp recordings in both cell
      types, ER-STIM1 was sufficient with perforated patch recordings. These results
      demonstrate that ARC and LRC currents are mediated by the same cellular
      populations of STIM1, Orai1, and Orai3, and suggest a complex role for both ER
      STIM1 and PM-STIM1 in regulating these store-independent Orai1/3 channels.

PMID- 24567510
TI  - Mutation of I696 and W697 in the TRP box of vanilloid receptor subtype I
      modulates allosteric channel activation.
AB  - The transient receptor potential vanilloid receptor subtype I (TRPV1) channel
      acts as a polymodal sensory receptor gated by chemical and physical stimuli. Like
      other TRP channels, TRPV1 contains in its C terminus a short, conserved domain
      called the TRP box, which is necessary for channel gating. Substitution of two
      TRP box residues-I696 and W697-with Ala markedly affects TRPV1's response to all
      activating stimuli, which indicates that these two residues play a crucial role
      in channel gating. We systematically replaced I696 and W697 with 18 native l
      amino acids (excluding cysteine) and evaluated the effect on voltage- and
      capsaicin-dependent gating. Mutation of I696 decreased channel activation by
      either voltage or capsaicin; furthermore, gating was only observed with
      substitution of hydrophobic amino acids. Substitution of W697 with any of the 18
      amino acids abolished gating in response to depolarization alone, shifting the
      threshold to unreachable voltages, but not capsaicin-mediated gating. Moreover,
      vanilloid-activated responses of W697X mutants showed voltage-dependent gating
      along with a strong voltage-independent component. Analysis of the data using an
      allosteric model of activation indicates that mutation of I696 and W697 primarily
      affects the allosteric coupling constants of the ligand and voltage sensors to
      the channel pore. Together, our findings substantiate the notion that inter-
      and/or intrasubunit interactions at the level of the TRP box are critical for
      efficient coupling of stimulus sensing and gate opening. Perturbation of these
      interactions markedly reduces the efficacy and potency of the activating stimuli.
      Furthermore, our results identify these interactions as potential sites for
      pharmacological intervention.

PMID- 24567511
TI  - Long alpha helices projecting from the membrane as the dimer interface in the
      voltage-gated H(+) channel.
AB  - The voltage-gated H(+) channel (Hv) is a H(+)-permeable voltage-sensor domain
      (VSD) protein that consists of four transmembrane segments (S1-S4). Hv assembles
      as a dimeric channel and two transmembrane channel domains function
      cooperatively, which is mediated by the coiled-coil assembly domain in the
      cytoplasmic C terminus. However, the structural basis of the interdomain
      interactions remains unknown. Here, we provide a picture of the dimer
      configuration based on the analyses of interactions among two VSDs and a coiled
      coil domain. Systematic mutations of the linker region between S4 of VSD and the
      coiled-coil showed that the channel gating was altered in the helical periodicity
      with the linker length, suggesting that two domains are linked by helices. Cross
      linking analyses revealed that the two S4 helices were situated closely in the
      dimeric channel. The interaction interface between the two S4 and the assembly
      interface of the coiled-coil domain were aligned in the same direction based on
      the phase angle calculation along alpha helices. Collectively, we propose that
      continuous helices stretching from the transmembrane to the cytoplasmic region in
      the dimeric interface regulate the channel activation in the Hv dimer.

PMID- 24567512
TI  - Illuminating the base of the annelid tree using transcriptomics.
AB  - Annelida is one of three animal groups possessing segmentation and is central in
      considerations about the evolution of different character traits. It has even
      been proposed that the bilaterian ancestor resembled an annelid. However, a
      robust phylogeny of Annelida, especially with respect to the basal relationships,
      has been lacking. Our study based on transcriptomic data comprising 68,750
      170,497 amino acid sites from 305 to 622 proteins resolves annelid relationships,
      including Chaetopteridae, Amphinomidae, Sipuncula, Oweniidae, and Magelonidae in
      the basal part of the tree. Myzostomida, which have been indicated to belong to
      the basal radiation as well, are now found deeply nested within Annelida as
      sister group to Errantia in most analyses. On the basis of our reconstruction of
      a robust annelid phylogeny, we show that the basal branching taxa include a huge
      variety of life styles such as tube dwelling and deposit feeding, endobenthic and
      burrowing, tubicolous and filter feeding, and errant and carnivorous forms.
      Ancestral character state reconstruction suggests that the ancestral annelid
      possessed a pair of either sensory or grooved palps, bicellular eyes, biramous
      parapodia bearing simple chaeta, and lacked nuchal organs. Because the oldest
      fossil of Annelida is reported for Sipuncula (520 Ma), we infer that the early
      diversification of annelids took place at least in the Lower Cambrian. 

PMID- 24567514
TI  - Cancer evolution: the final frontier of precision medicine?

PMID- 24567513
TI  - A comprehensive, high-resolution map of a gene's fitness landscape.
AB  - Mutations are central to evolution, providing the genetic variation upon which
      selection acts. A mutation's effect on the suitability of a gene to perform a
      particular function (gene fitness) can be positive, negative, or neutral.
      Knowledge of the distribution of fitness effects (DFE) of mutations is
      fundamental for understanding evolutionary dynamics, molecular-level genetic
      variation, complex genetic disease, the accumulation of deleterious mutations,
      and the molecular clock. We present comprehensive DFEs for point and codon
      mutants of the Escherichia coli TEM-1 beta-lactamase gene and missense mutations
      in the TEM-1 protein. These DFEs provide insight into the inherent benefits of
      the genetic code's architecture, support for the hypothesis that mRNA stability
      dictates codon usage at the beginning of genes, an extensive framework for
      understanding protein mutational tolerance, and evidence that mutational effects
      on protein thermodynamic stability shape the DFE. Contrary to prevailing
      expectations, we find that deleterious effects of mutation primarily arise from a
      decrease in specific protein activity and not cellular protein levels. 

PMID- 24567515
TI  - The role of body mass index in survival outcome for lymphoma patients: US
      intergroup experience.
AB  - BACKGROUND: The role of body mass index (BMI) in survival outcomes is
      controversial among lymphoma patients. We evaluated the association between BMI
      at study entry and failure-free survival (FFS) and overall survival (OS) in three
      phase III clinical trials, among patients with diffuse large B-cell lymphoma
      (DLBCL), follicular lymphoma (FL) and Hodgkin's lymphoma (HL). PATIENTS AND
      METHODS: A total of 537, 730 and 282 patients with DLBCL, HL and FL were included
      in the analysis. Baseline patient and clinical characteristics, treatment
      received and clinical outcomes were compared across BMI categories. RESULTS:
      Among patients with DLBCL, HL and FL, the median age was 70, 33 and 56; 29%, 29%
      and 37% were obese and 38%, 27% and 37% were overweight, respectively. Age was
      significantly different among BMI groups in all three studies. Higher BMI groups
      tended to have more favorable prognosis factors at study entry among DLBCL and HL
      patients. BMI was not associated with clinical outcome with P-values of 0.89,
      0.30 and 0.40 for FFS, and 0.64, 0.67 and 0.09 for OS, for patients with DLBCL,
      HL and FL, respectively. The association remains non-significant after adjusting
      for other clinical factors in the Cox model. A subset analysis of males with
      DLBCL treated on R-CHOP revealed no differences in FFS (P = 0.48) or OS (P =
      0.58). CONCLUSION: BMI was not significantly associated with clinical outcomes
      among patients with DLBCL, HD or FL, in three prospective phase III clinical
      trials. The findings contradict some previous reports of similar investigations.
      Further work is required to understand the observed discrepancies.

PMID- 24567517
TI  - Plasma testosterone in the general population, cancer prognosis and cancer risk:
      a prospective cohort study.
AB  - BACKGROUND: Testosterone is an important anabolic hormone in humans and in vitro
      testosterone stimulates growth of lung and colon cancer cells. We tested the
      hypothesis that plasma testosterone associate with increased risk of cancer and
      with increased risk of early death after cancer. MATERIALS AND METHODS: Plasma
      testosterone was measured in 8771 20- to 94-year-old men and women who
      participated in a prospective study of the general population. Participants were
      included in 1981-1983 and followed for a median of 22 years (range: 0-30 years).
      RESULTS: During follow-up, 1140 men and 809 women developed cancer. For risk of
      early death after cancer, for men, after adjustment for age at diagnosis, tumour
      stage at diagnosis, and time since blood-sampling, the hazard ratio was 1.30 [95%
      confidence interval (CI) 1.03-1.65] for the 2nd quintile, 1.31 (1.02-1.67) for
      the 3rd quintile, 1.52 (1.19-1.93) for the 4th quintile, and 1.52 (1.20-1.91) for
      the 5th quintile, versus the 1st quintile. For women, corresponding hazard ratios
      were 1.09 (0.81-1.46), 1.17 (0.86-1.59), 1.03 (0.76-1.39), and 1.80 (1.32-2.46).
      For risk of cancer, multifactorially adjusted hazard ratios for risk of any
      cancer were 1.07 (95% CI 0.98-1.18) and 1.06 (0.93-1.22) for men and women,
      respectively, when testosterone doubled. For both men and women, a doubling of
      testosterone was not associated with risk of any cancer type. CONCLUSIONS: In
      this prospective study of 8771 men and women from the general population followed
      for >30 years, increased levels of testosterone were associated with a 30%-80%
      increased risk of early death after cancer, but unchanged risk of incident
      cancer.

PMID- 24567516
TI  - Cisplatin, 5-fluorouracil, and cetuximab (PFE) with or without cilengitide in
      recurrent/metastatic squamous cell carcinoma of the head and neck: results of the
      randomized phase I/II ADVANTAGE trial (phase II part).
AB  - BACKGROUND: Recurrent and/or metastatic squamous cell carcinoma of the head and
      neck (R/M-SCCHN) overexpresses alphavbeta5 integrin. Cilengitide selectively
      inhibits alphavbeta3 and alphavbeta5 integrins and is investigated as a treatment
      strategy. PATIENTS AND METHODS: The phase I/II study ADVANTAGE evaluated
      cilengitide combined with cisplatin, 5-fluorouracil, and cetuximab (PFE) in R/M
      SCCHN. The phase II part reported here was an open-label, randomized, controlled
      trial investigating progression-free survival (PFS). Patients received up to six
      cycles of PFE alone or combined with cilengitide 2000 mg once (CIL1W) or twice
      (CIL2W) weekly. Thereafter, patients received maintenance therapy (cilengitide
      arms: cilengitide plus cetuximab; PFE-alone arm: cetuximab only) until disease
      progression or unacceptable toxicity. RESULTS: One hundred and eighty-two
      patients were treated. Median PFS per investigator read was similar for CIL1W +
      PFE, CIL2W + PFE, and PFE alone (6.4, 5.6, and 5.7 months, respectively).
      Accordingly, median overall survival and objective response rates were not
      improved with cilengitide (12.4 months/47%, 10.6 months/27%, and 11.6 months/36%,
      respectively). No clinically meaningful safety differences were observed between
      groups. None of the tested biomarkers (expression of integrins, CD31, Ki-67,
      vascular endothelial growth factor receptor 2, vascular endothelial-cadherin,
      type IV collagen, epidermal growth factor receptor, or p16 for human
      papillomavirus) were predictive of outcome. CONCLUSION: Neither of the
      cilengitide-containing regimens demonstrated a PFS benefit over PFE alone in R/M
      SCCHN patients.

PMID- 24567518
TI  - Retroperitoneal sarcomas: patterns of care at diagnosis, prognostic factors and
      focus on main histological subtypes: a multicenter analysis of the French Sarcoma
      Group.
AB  - BACKGROUND: Retroperitoneal sarcomas (RPS) are heterogeneous. No previous study
      has investigated the impact of specialized surgery, evaluated locoregional
      relapse (LRR), abdominal sarcomatosis and distant metastatic relapse as separate
      events, or considered histological subtypes separately. This study addresses
      these specific points in a homogeneous cohort of patients with completely
      resected primary RPS. PATIENTS AND METHODS: We conducted a retrospective analysis
      of adult patients diagnosed with a RPS between 1 January 1988 and 31 December
      2008 and eventually referred to one of 12 centers of the French Sarcoma Group.
      All cases were centrally reviewed by an expert pathologist. RESULTS: Five hundred
      eighty-six patients were included. Median follow-up was 6.5 years [95% confidence
      interval (CI) 5.9-7.1]. Five hundred thirty-seven patients had localized disease
      and 389 patients (76%) had macroscopically complete resection of the tumor. In
      this latter group, the 5-year LRR-free survival rate was 46% [41-52] and the 5
      year overall survival (OS) rate was 66% [61-71]. In multivariate analysis,
      gender, adjacent organ involvement, specialization of the surgeon, piecemeal
      resection and perioperative radiotherapy were independently associated with LRR.
      Specialization of the surgeon and piecemeal resection were independently
      associated with abdominal sarcomatosis whereas histology and adjacent organ
      involvement were independently associated with distant metastasis. Age, gender,
      grade, adjacent organ involvement and piecemeal resection were significantly
      associated with OS. Prognostic factors for LRR and OS were analyzed in well
      differentiated and dedifferentiated liposarcomas and leiomyosarcomas. Grade 3 was
      an independent prognostic factor for OS of dedifferentiated liposarcomas.
      CONCLUSION: This study underlines the crucial role of pretherapeutic assessment
      and meticulous histological examination of RPS as well as the need to consider
      histological subtypes separately. Surgery in a specialized center and avoidance
      of piecemeal resection stand out as the two most important prognostic factors for
      RPS and highlight the importance of treating these patients in specialized
      centers.

PMID- 24567521
TI  - The dual impact of antiretroviral therapy and sexual behaviour changes on HIV
      epidemiologic trends in Uganda: a modelling study.
AB  - OBJECTIVES: Antiretroviral therapy (ART) availability in a population may
      influence risky sexual behaviour. We examine the potential impact of ART on the
      HIV epidemic, incorporating evidence for the impact that ART may have on risky
      sexual behaviour. METHODS: A mathematical model, parameterised using site
      specific data from Uganda and worldwide literature review, was used to examine
      the likely impact of ART on HIV epidemiologic trends. We varied assumptions about
      rates of initiating ART, and changes in sexual partner turnover rates. RESULTS:
      Modelling suggests that ART will reduce HIV incidence over 20 years, and increase
      prevalence. Even in the optimistic scenario of ART enrollment beginning after
      just five months of infection (in HIV stage 2), prevalence is estimated to rise
      from a baseline of 10.5% and 8.3% among women and men, respectively, to at least
      12.1% and 10.2%, respectively. It will rise further if sexual disinhibition
      occurs or infectiousness while on ART is slightly higher (2% female to male,
      rather than 0.5%). The conditions required for ART to reduce prevalence over this
      period are likely too extreme to be achievable. For example, if ART enrolment
      begins in HIV stage 1 (within the first 5 months of infection), and if risky
      sexual behaviour does not increase, then 3 of our 11 top fitting results estimate
      a potential drop in HIV prevalence by 2025. If sexual risk taking rises, it will
      have a large additional impact on expected HIV prevalence. Prevalence will rise
      despite incidence falling, because ART extends life expectancy. CONCLUSIONS: HIV
      prevalence will rise. Even small increases in partner turnover rates will lead to
      an additional substantial increase in HIV prevalence. Policy makers are urged to
      continue HIV prevention activities, including promoting sex education, and to be
      prepared for a higher than previously suggested number of HIV infected people in
      need of treatment.

PMID- 24567522
TI  - Sexually transmitted infections among women attending a Norwegian Sexual Assault
      Centre.
AB  - OBJECTIVES: The objective was to describe the prevalence of sexually transmitted
      infections (STI) and blood-borne viruses (BBV), and prophylactic treatment
      offered to female postpubertal patients attending a Norwegian Sexual Assault
      Centre (SAC). We wanted to evaluate whether STIs diagnosed at the initial visit
      could have been assault-transmitted, and to explore whether background and
      assault characteristics were associated with diagnosed STI/BBV. METHODS: We
      included postpubertal females >=12 years of age attending the SAC within 1 week
      of the assault. Data were collected from records. We conducted a retrospective,
      descriptive study, and used logistic regression analysis. RESULTS: Among 412
      patients with a median age of 21 years, 35 patients had an STI (8.5%), two of
      which probably were assault-transmitted. Chlamydia trachomatis was the dominating
      agent, detected in 25 patients (6.4%). At serology screening, 3.7% tested
      positive for hepatitis C and/or hepatitis B core antibody. Patient age 16-19
      years was associated with STI, while BBV positives were older. Non-Western
      assailant was associated with STI, while substance abuse was associated with STI
      and BBV. In order to prevent potential transmission of STI not identified at the
      initial visit, 91% accepted prophylaxis against bacterial STI, while antiviral
      prophylaxis was offered to less than one-fifth of the patients. CONCLUSIONS: The
      C trachomatis prevalence among the sexual assault patients was lower than in a
      comparable clinical population. The STI was suspected to be assault-transmitted
      in only two cases.

PMID- 24567523
TI  - Quantitative lung perfused blood volume imaging on dual-energy CT: capability for
      quantitative assessment of disease severity in patients with acute pulmonary
      thromboembolism.
AB  - BACKGROUND: Regional iodine distribution assessment on dual-energy computed
      tomography (DECT) has been suggested as useful for management of acute pulmonary
      thromboembolism (APTE) patients. However, no reported studies have made a direct
      comparison between quantitatively assessed DECT and right-to-left ventricular
      (RV/LV) ratio on CT for differentiation of right heart dysfunction (RHD) from non
      right heart dysfunction (NRHD) in APTE patients. PURPOSE: To determine the
      capability of DECT for differentiation of RHD from NRHD in APTE patients.
      MATERIAL AND METHODS: Thirteen APTE patients underwent DECT and echocardiography
      at onset of APTE. Patients were divided into RHD (n = 7) and NRHD (n = 6) groups
      based on echocardiography. A normalized lung perfused blood volume map was
      generated, and two kinds of overall perfusion (OP) index were determined, one
      placed over each lung field (OP index A) and as the average from six regions of
      interest (ROIs) placed over each lung field (OP index B). The heterogeneity index
      was also determined as the standard deviation for the six ROIs. RV/LV ratio
      evaluations were also performed. To assess differences between the two groups,
      each index was statistically compared with the Mann-Whitney U test. The receiver
      operating curve-based positive test was then performed to determine the feasible
      threshold value for dividing patients into the two groups. Finally,
      differentiation capabilities of the indexes were compared using McNemar's test.
      RESULTS: Significant differences between the two groups were found for both OP
      indexes and RV/LV ratio (P < 0.05). For each of the feasible threshold values,
      accuracy of each OP index with and without RV/LV ratio was better than that of
      the RV/LV ratio. CONCLUSION: Quantitative DECT has good potential for
      differentiation of APTE patients with and without right heart dysfunction.

PMID- 24567524
TI  - IL-17A gene transfer induces bone loss and epidermal hyperplasia associated with
      psoriatic arthritis.
AB  - BACKGROUND: Psoriatic arthritis (PsA) is a chronic inflammatory disease
      characterised by clinical features that include bone loss and epidermal
      hyperplasia. Aberrant cytokine expression has been linked to joint and skin
      pathology; however, it is unclear which cytokines are critical for disease
      initiation. Interleukin 17A (IL-17A) participates in many pathological immune
      responses; however, its role in PsA has not been fully elucidated. OBJECTIVE: To
      determine the role of IL-17A in epidermal hyperplasia and bone destruction
      associated with psoriatic arthritis. DESIGN: An in vivo gene transfer approach
      was used to investigate the role of IL-17A in animal models of inflammatory
      (collagen-induced arthritis) and non-inflammatory (receptor activator of NF
      kappaB ligand (RANKL)-gene transfer) bone loss. RESULTS: IL-17A gene transfer
      induced the expansion of IL-17RA(+)CD11b(+)Gr1(low) osteoclast precursors and a
      concomitant elevation of biomarkers indicative of bone resorption. This occurred
      at a time preceding noticeable joint inflammation, suggesting that IL-17A is
      critical for the induction of pathological bone resorption through direct
      activation of osteoclast precursors. Moreover, IL-17A induced a second myeloid
      population CD11b(+)Gr1(high) neutrophil-like cells, which was associated with
      cutaneous pathology including epidermal hyperplasia, parakeratosis and Munro's
      microabscesses formation. CONCLUSIONS: Collectively, these data support that IL
      17A can play a key role in the pathogenesis of inflammation-associated arthritis
      and/or skin disease, as observed in PsA.

PMID- 24567526
TI  - The multifunctional growth factor midkine promotes proliferation and migration in
      pancreatic cancer.
AB  - Pancreatic ductal adenocarcinoma (PDAC) has a devastating prognosis among solid
      tumors and despite increased knowledge of the molecular mechanisms contributing
      to progression and metastasis, minimal progress has been done in establishing new
      targeted therapies for this deadly disease. The expression of the multifunctional
      growth/differentiation factor midkine (MK) promotes a variety of cellular
      functions leading to increased angiogenesis, proliferation, migration, and
      survival. Moreover, MK is intensively discussed as a potential new-therapy target
      and as biomarker for cancer progression and chemotherapeutic resistance in
      multiple cancers. Therefore, the present study investigated the molecular role of
      MK in pancreatic cancer. It was found that MK is elevated in PDAC and
      differentially expressed in other histologic subtypes of pancreatic cancer,
      whereas normal pancreatic cells did not express MK, thus making it an attractive
      candidate for targeted therapies. As a secreted growth/differentiation factor, MK
      was investigated as a biomarker in clinical serum specimens using ELISA. In
      addition, knockdown studies of MK revealed a link to proliferation and migration
      status in vitro. Finally, upstream signaling pathways were analyzed, with TNF
      alpha and EGF being the main inductors of MK expression in PDAC. IMPLICATIONS:
      This study presents novel MK functions and new upstream signaling effectors that
      induce its expression to promote PDAC and therefore defines an attractive new
      therapeutic target in pancreatic cancer.

PMID- 24567525
TI  - Stimulation of the soluble guanylate cyclase (sGC) inhibits fibrosis by blocking
      non-canonical TGFbeta signalling.
AB  - OBJECTIVES: We have previously described the antifibrotic role of the soluble
      guanylate cyclase (sGC). The mode of action, however, remained elusive. In the
      present study, we describe a novel link between sGC signalling and transforming
      growth factor beta (TGFbeta) signalling that mediates the antifibrotic effects of
      the sGC. METHODS: Human fibroblasts and murine sGC knockout fibroblasts were
      treated with the sGC stimulator BAY 41-2272 or the stable cyclic guanosine
      monophosphate (cGMP) analogue 8-Bromo-cGMP and stimulated with TGFbeta. sGC
      knockout fibroblasts were isolated from sGCI(fl/fl) mice, and recombination was
      induced by Cre-adenovirus. In vivo, we studied the antifibrotic effects of BAY 41
      2272 in mice overexpressing a constitutively active TGF-beta1 receptor. RESULTS:
      sGC stimulation inhibited TGFbeta-dependent fibroblast activation and collagen
      release. sGC knockout fibroblasts confirmed that the sGC is essential for the
      antifibrotic effects of BAY 41-2272. Furthermore, 8-Bromo-cGMP reduced TGFbeta
      dependent collagen release. While nuclear p-SMAD2 and 3 levels, SMAD reporter
      activity and transcription of classical TGFbeta target genes remained unchanged,
      sGC stimulation blocked the phosphorylation of ERK. In vivo, sGC stimulation
      inhibited TGFbeta-driven dermal fibrosis but did not change p-SMAD2 and 3 levels
      and TGFbeta target gene expression, confirming that non-canonical TGFbeta
      pathways mediate the antifibrotic sGC activity. CONCLUSIONS: We elucidated the
      antifibrotic mode of action of the sGC that increases cGMP levels, blocks non
      canonical TGFbeta signalling and inhibits experimental fibrosis. Since sGC
      stimulators have shown excellent efficacy and tolerability in phase 3 clinical
      trials for pulmonary arterial hypertension, they may be further developed for the
      simultaneous treatment of fibrosis and vascular disease in systemic sclerosis.

PMID- 24567528
TI  - Adaptation to Early-Stage Nonfluent/Agrammatic Variant Primary Progressive
      Aphasia: A First-Person Account.
AB  - Primary progressive aphasia (PPA) is a young-onset neurodegenerative disorder
      characterized by declining language ability. The nonfluent/agrammatic variant of
      PPA (PPA-G) has the core features of agrammatism in language production and
      effortful, halting speech. As with other frontotemporal spectrum disorders, there
      is currently no cure for PPA, nor is it possible to slow the course of
      progression. The primary goal of treatment is therefore palliative in nature.
      However, there is a paucity of published information about strategies to make
      meaningful improvements to the quality of life of people with PPA, particularly
      in the early stages of the disease where any benefit could most be appreciated by
      the affected person. This report describes a range of strategies and adaptations
      designed to improve the quality of life of a person with early-stage PPA-G, based
      on my experience under the care of a multidisciplinary medical team. 

PMID- 24567527
TI  - TRAP1 regulates proliferation, mitochondrial function, and has prognostic
      significance in NSCLC.
AB  - The TNF receptor-associated protein 1 (TRAP1) is a mitochondrial HSP that has
      been related to drug resistance and protection from apoptosis in colorectal and
      prostate cancer. Here, the effect of TRAP1 ablation on cell proliferation,
      survival, apoptosis, and mitochondrial function was determined in non-small cell
      lung cancer (NSCLC). In addition, the prognostic value of TRAP1 was evaluated in
      patients with NSCLC. These results demonstrate that TRAP1 knockdown reduces cell
      growth and clonogenic cell survival. Moreover, TRAP1 downregulation impairs
      mitochondrial functions such as ATP production and mitochondrial membrane
      potential as measured by TMRM (tetramethylrhodamine methylester) uptake, but it
      does not affect mitochondrial density or mitochondrial morphology. The effect of
      TRAP1 silencing on apoptosis, analyzed by flow cytometry and immunoblot
      expression (cleaved PARP, caspase-9, and caspase-3) was cell line and context
      dependent. Finally, the prognostic potential of TRAP1 expression in NSCLC was
      ascertained via immunohistochemical analysis which revealed that high TRAP1
      expression was associated with increased risk of disease recurrence (univariate
      analysis, P = 0.008; multivariate analysis, HR: 2.554; 95% confidence interval,
      1.085-6.012; P = 0.03). In conclusion, these results demonstrate that TRAP1
      impacts the viability of NSCLC cells, and that its expression is prognostic in
      NSCLC. IMPLICATIONS: TRAP1 controls NSCLC proliferation, apoptosis, and
      mitochondrial function, and its status has prognostic potential in NSCLC.

PMID- 24567529
TI  - Targeting S1P1 receptor protects against murine immunological hepatic injury
      through myeloid-derived suppressor cells.
AB  - Although FTY720 may alter migration and homing of lymphocytes via sphingosine-1
      phosphate (S1P) receptors, our recent studies indicated that FTY720 directly
      controls the differentiation of Th1 cells to regulatory T cells (Tregs) by
      targeting S1P1. However, the pharmacological function of FTY720 in immunological
      hepatic injury remains unknown. In this study, the role and regulatory signaling
      pathway of S1P receptor were investigated using a pharmacological approach in
      immune-mediated hepatic injury (IMH). In the context of IMH, FTY720 significantly
      ameliorated mortality and hepatic pathology. In FTY720-treated mice, recruited
      CD11b(+)Gr1(+) myeloid-derived suppressor cells (MDSCs) mediate protection
      against IMH and are functional suppressive immune modulators that result in fewer
      IFN-gamma-producing Th1 cells and more Foxp3(+) Tregs. In agreement, FTY720
      treated MDSCs promote the reciprocal differentiation between Th1 cells and Tregs
      in vitro and in vivo. Mechanistically, FTY720 treatment induced inducible NO
      synthase expression and NO production in MDSCs. Pharmacologic inhibition of
      inducible NO synthase completely eliminates MDSC suppressive function and
      eradicates their inducible effects on T cell differentiation. Finally, the mTOR
      inhibitor, rapamycin, photocopies the effects of FTY720 on MDSCs, implicating
      mTOR as a downstream effector of S1P1 signaling. This study identifies MDSCs as
      an essential component that provides protection against IMH following FTY720 or
      rapamycin treatment, validating the S1P1-mTOR signaling axis as a potential
      therapeutic target in hepatic injury.

PMID- 24567530
TI  - Tissue distribution and dependence of responsiveness of human antigen-specific
      memory B cells.
AB  - Memory B cells (mBCs) are a key to immunologic memory, yet their distribution
      within lymphoid organs and the individual role of these for mBC functionality
      remain largely unknown. This study characterized the distribution and phenotype
      of human (Ag-specific) mBCs in peripheral blood (PB), spleen, tonsil, and bone
      marrow. We found that the spleen harbors most mBCs, followed by tonsils, BM, and
      PB, and we detected no major differences in expression of markers associated with
      higher maturity. Testing the distribution of tetanus toxoid-specific (TT(+)) mBCs
      revealed their presence in PB during steady state, yet absolute numbers suggested
      their largest reservoir in the spleen, followed by tonsils. To explore the role
      of both tissues in the maintenance of reactive B cell memory, we revaccinated
      controls and splenectomized and tonsillectomized individuals with TT. All donor
      groups exhibited comparable emergence of anti-TT IgG, TT(+) plasma cells, and
      TT(+) mBCs in the PB, together with similar molecular characteristics of TT(+)
      plasma cells. In summary, human mBCs recirculate through PB and reside in
      different lymphoid organs that do not reflect different mBC maturity stages. The
      spleen and tonsil, although harboring the largest number of overall and TT(+)
      mBCs, appear to be dispensable to preserve adequate responsiveness to secondary
      antigenic challenge. 

PMID- 24567531
TI  - Regulator of fatty acid metabolism, acetyl coenzyme a carboxylase 1, controls T
      cell immunity.
AB  - Fatty acids (FAs) are essential constituents of cell membranes, signaling
      molecules, and bioenergetic substrates. Because CD8(+) T cells undergo both
      functional and metabolic changes during activation and differentiation, dynamic
      changes in FA metabolism also occur. However, the contributions of de novo
      lipogenesis to acquisition and maintenance of CD8(+) T cell function are unclear.
      In this article, we demonstrate the role of FA synthesis in CD8(+) T cell
      immunity. T cell-specific deletion of acetyl coenzyme A carboxylase 1 (ACC1), an
      enzyme that catalyzes conversion of acetyl coenzyme A to malonyl coenzyme A, a
      carbon donor for long-chain FA synthesis, resulted in impaired peripheral
      persistence and homeostatic proliferation of CD8(+) T cells in naive mice. Loss
      of ACC1 did not compromise effector CD8(+) T cell differentiation upon listeria
      infection but did result in a severe defect in Ag-specific CD8(+) T cell
      accumulation because of increased death of proliferating cells. Furthermore, in
      vitro mitogenic stimulation demonstrated that defective blasting and survival of
      ACC1-deficient CD8(+) T cells could be rescued by provision of exogenous FA.
      These results suggest an essential role for ACC1-mediated de novo lipogenesis as
      a regulator of CD8(+) T cell expansion, and may provide insights for therapeutic
      targets for interventions in autoimmune diseases, cancer, and chronic infections.

PMID- 24567533
TI  - Ligation of surface Ig by gut-derived antigen positively selects chicken bursal
      and peripheral B cells.
AB  - In many mammals and birds, B cell lymphopoiesis takes place in GALT, such as the
      avian bursa of Fabricius. Although BCR expression is sufficient for bursal
      colonization, the role of BCR ligation in the later stages of bursal B cell
      lymphopoiesis remains elusive. To address this directly, we introduced a surface
      Ig-related construct with defined Ag specificity containing the Ag-binding
      portion of a lamprey variable lymphocyte receptor specific for PE fused to a
      truncated chicken MU-chain (VLR(PE)TMU) into developing chick embryos. VLR(PE)TMU
      expression supports bursal follicle colonization, clonal expansion, and Ig V gene
      diversification. VLR(PE)TMU-expressing B cells migrate to the periphery in the
      absence of the Ag starting from day 18 of embryogenesis. VLR(PE)TMU-expressing B
      cells declined rapidly in the bursa and periphery in the absence of Ag after
      hatch; however, intrabursal injection of PE prolonged survival of VLR(PE)TMU(+)
      bursal and peripheral B cells. Intrabursal introduction of Ag increased
      emigration of short-lived LT2(+) B cells. Peripheral VLR(PE)TMU(+) B cells were
      maintained following intrabursal PE application and contained both short-lived
      LT2(+) and long-lived LT2(-) B cells. In the chicken bursa, the later stages of B
      cell development occur in the presence of gut-derived Ag; therefore, we conclude
      that Ag-mediated ligation of BCR in bursal B cells acts to positively select
      bursal B cells into both short-lived and long-lived peripheral B cell
      populations. 

PMID- 24567532
TI  - Tim-3 directly enhances CD8 T cell responses to acute Listeria monocytogenes
      infection.
AB  - T cell Ig and mucin domain (Tim) 3 is a surface molecule expressed throughout the
      immune system that can mediate both stimulatory and inhibitory effects. Previous
      studies have provided evidence that Tim-3 functions to enforce CD8 T cell
      exhaustion, a dysfunctional state associated with chronic stimulation. In
      contrast, the role of Tim-3 in the regulation of CD8 T cell responses to acute
      and transient stimulation remains undefined. To address this knowledge gap, we
      examined how Tim-3 affects CD8 T cell responses to acute Listeria monocytogenes
      infection. Analysis of wild-type (WT) mice infected with L. monocytogenes
      revealed that Tim-3 was transiently expressed by activated CD8 T cells and was
      associated primarily with acquisition of an effector phenotype. Comparison of
      responses to L. monocytogenes by WT and Tim-3 knockout (KO) mice showed that the
      absence of Tim-3 significantly reduced the magnitudes of both primary and
      secondary CD8 T cell responses, which correlated with decreased IFN-gamma
      production and degranulation by Tim-3 KO cells stimulated with peptide Ag ex
      vivo. To address the T cell-intrinsic role of Tim-3, we analyzed responses to L.
      monocytogenes infection by WT and Tim-3 KO TCR-transgenic CD8 T cells following
      adoptive transfer into a shared WT host. In this setting, the accumulation of CD8
      T cells and the generation of cytokine-producing cells were significantly reduced
      by the lack of Tim-3, demonstrating that this molecule has a direct effect on CD8
      T cell function. Combined, our results suggest that Tim-3 can mediate a
      stimulatory effect on CD8 T cell responses to an acute infection. 

PMID- 24567536
TI  - The prevalence and impact of intimate partner violence on maternal distress in a
      community of low-income Bangladeshi and displaced ethnic Bihari mothers: Dhaka,
      2008-2009.
AB  - Low-income, ethnic, and/or displaced mothers are frequently victimized; we
      explored the burden of intimate partner violence (IPV) among such women. Teams
      administered IPV and maternal distress questionnaires to quantify victimization
      after the birth of a child. Of 250 mothers reporting abuse, 133 (53%) reported
      their husband hitting; 111 (44%) kicking, dragging, or beating; 61 (24%) choking
      or burning; and 33 (13%) injuring them with a knife or gun (12 case-patients per
      100 person-years). Women who experienced more forms of victimization reported
      more distress (p = .01). Mothers in this low-income community experienced severe
      victimization and distress. 

PMID- 24567537
TI  - Correlates of perceived helpfulness of mental health professionals following
      disclosure of sexual assault.
AB  - A diverse sample of more than 365 adult sexual assault survivors, recruited from
      college and community sources, was surveyed about sexual assault experiences,
      post-assault factors, and perceived helpfulness of and satisfaction with mental
      health professionals. Regression analyses were conducted to identify factors
      associated with perceived helpfulness of and satisfaction with mental health
      professionals. Older age, higher posttraumatic stress disorder (PTSD), greater
      control over recovery, and more emotional support reactions were associated with
      positive perceptions of mental health professionals. Stranger offenders, greater
      resistance during assault, high victim post-assault upset, and blaming social
      reactions from others were associated with negative perceptions of mental health
      professionals. 

PMID- 24567538
TI  - A qualitative exploration of researcher trauma and researchers' responses to
      investigating sexual violence.
AB  - Vicarious trauma can be a problem for those who work and research in areas where
      clients or participants are survivors of sexual violence. The aim of this study
      was to explore the trauma experiences of sexual violence researchers from
      different countries, identifying the issues that traumatized them and the
      protective strategies they found effective. This article reports on a moderated
      electronic discussion board run for 4 weeks from September to October 2009 and
      four purposeful interviews. A total of 15 researchers participated, 4 males and
      11 females. Institutions and organizations researching in this area should
      consider researcher safety in project design. 

PMID- 24567534
TI  - Noncoding RNAs and LRRFIP1 regulate TNF expression.
AB  - Noncoding RNAs have been implicated in the regulation of expression of numerous
      genes; however, the mechanism is not fully understood. We identified
      bidirectional, long noncoding RNAs upstream of the TNF gene using five different
      methods. They arose in a region where the repressors LRRFIP1, EZH2, and SUZ12
      were demonstrated to bind, suggesting a role in repression. The noncoding RNAs
      were polyadenylated, capped, and chromatin associated. Knockdown of the noncoding
      RNAs was associated with derepression of TNF mRNA and diminished binding of
      LRRFIP1 to both RNA targets and chromatin. Overexpression of the noncoding RNAs
      led to diminished expression of TNF and recruitment of repressor proteins to the
      locus. One repressor protein, LRRFIP1, bound directly to the noncoding RNAs.
      These data place the noncoding RNAs upstream of TNF gene as central to the
      transcriptional regulation. They appear to serve as a platform for the assembly
      of a repressive complex. 

PMID- 24567539
TI  - Alcohol, testosterone and suicide.

PMID- 24567540
TI  - Electroconvulsive therapy for the neurological and psychiatric manifestations of
      multiple system atrophy.

PMID- 24567541
TI  - Combination clozapine and electroconvulsive therapy in a patient with
      schizophrenia and comorbid intellectual disability.

PMID- 24567542
TI  - Detection of diisocyanates in nesting material associated with mortality in
      pigeon chicks.
AB  - Diisocyanates, commonly used in the production of polyurethane foams, paints,
      elastomers, varnishes, and coatings, are considered among the most hazardous
      inhalation toxicants. The present report describes 2 unusual cases of mortality
      in pigeon chicks associated with nesting material contaminated by diisocyanates.
      Case 1 was submitted by a racing pigeon breeder who had lost all the hatchlings
      (n = 125) following replacement of the nesting material with a different lot. All
      adult birds appeared healthy, and hatchability was not significantly affected,
      but hatchlings became lethargic and dyspneic after a day of hatch. At necropsy,
      dark wet lungs were found in the hatchlings. Case 2 was submitted by a show
      roller pigeon breeder. In this case, the owner reported lower hatchability, and
      all hatchlings (approximately 100) died within 2 days of hatching with clinical
      signs similar to the first case. Necropsy did not reveal any significant
      findings. For both cases, nesting materials were screened for toxic compounds
      using gas chromatography-mass spectrometry. Toluene-2,4-diisocyanate
      (approximately 190-290 ppm) and 4,4'-methylene diphenyl diisocyanate
      (unquantified) were detected in the nesting pads. While there is very limited
      information on toxicosis in birds, there are reports of inhalant exposure of
      diisocyanates causing pulmonary edema and death in various mammalian species.
      Although cause-effect relationship of mortality and the nesting material was not
      established in the present cases, the presence of toxic compounds in the nesting
      materials is a cause for concern. Further investigation is needed to determine
      the prevalence and toxicity of diisocyanates-contaminated nesting material in
      avian species. 

PMID- 24567543
TI  - Differential diagnosis of Goatpox virus in Taiwan by multiplex polymerase chain
      reaction assay and high-resolution melt analysis.
AB  - The A32L gene from a Goatpox virus (GTPV) strain isolated from a goat in Yunlin
      County (Taiwan) displays several substitutions compared with the sequence of the
      Kenyan GTPV vaccine strain SGP0240 and the Pellor GTPV strain. Samples from the
      skin lesions on 6 goats with GTPV infection or from goats with Orf virus (ORFV)
      infection were tested in a multiplex polymerase chain reaction (PCR) system that
      used primers GPF, GPR1, and GPR2 as well as previously published primers specific
      for ORFV. These primers were able to amplify either GTPV or ORFV without cross
      reactivity. A high-resolution melt analysis (HRMA) was carried out on amplified
      DNA from the skin lesions of 6 goats with GTPV infection and with the GTPV
      SGP0240 strain. The results indicated that the melting temperature profiles
      amplified from samples with Yunlin GTPV infection can be differentiated from the
      GTPV SGP0240 strain. The findings showed that a successful differential assay for
      these GTPVs had been developed. Accordingly, both methods can be used to detect
      and differentiate GTPV isolated from animals that may have either been vaccinated
      or been infected with a wild strain. The multiplex PCR and HRMA could be used on
      skin samples of suspected cases to serve as the front-line and confirmative
      assays, respectively, which will be beneficial to the eradication of GTPV. 

PMID- 24567544
TI  - jHeatmap: an interactive heatmap viewer for the web.
AB  - SUMMARY: The generation of large volumes of omics data to conduct exploratory
      studies has become feasible and is now extensively used to gain new insights in
      life sciences. The effective exploration of the generated data by experts is a
      crucial step for the successful extraction of knowledge from these datasets. This
      requires availability of intuitive and interactive visualization tools that can
      display complex data. Matrix heatmaps are graphical representations frequently
      used for the description of complex omics data. Here, we present jHeatmap, a web
      based tool that allows interactive matrix heatmap visualization and exploration.
      It is an adaptable javascript library designed to be embedded by means of basic
      coding skills into web portals to visualize data matrices as interactive and
      customizable heatmaps. AVAILABILITY: jHeatmap is freely available at the GitHub
      code repository at https://github.com/jheatmap/jheatmap. Working examples and the
      documentation may be found at http://jheatmap.github.io/jheatmap.

PMID- 24567545
TI  - iCall: a genotype-calling algorithm for rare, low-frequency and common variants
      on the Illumina exome array.
AB  - MOTIVATION: Next-generation genotyping microarrays have been designed with
      insights from 1000 Genomes Project and whole-exome sequencing studies. These
      arrays additionally include variants that are typically present at lower
      frequencies. Determining the genotypes of these variants from hybridization
      intensities is challenging because there is less support to locate the presence
      of the minor alleles when the allele counts are low. Existing algorithms are
      mainly designed for calling common variants and are notorious for failing to
      generate accurate calls for low-frequency and rare variants. Here, we introduce a
      new calling algorithm, iCall, to call genotypes for variants across the whole
      spectrum of allele frequencies. RESULTS: We benchmarked iCall against four of the
      most commonly used algorithms, GenCall, optiCall, illuminus and GenoSNP, as well
      as a post-processing caller zCall that adopted a two-stage calling design.
      Normalized hybridization intensities for 12 370 individuals genotyped on the
      Illumina HumanExome BeadChip were considered, of which 81 individuals were also
      whole-genome sequenced. The sequence calls were used to benchmark the accuracy of
      the genotype calling, and our comparisons indicated that iCall outperforms all
      four single-stage calling algorithms in terms of call rates and concordance,
      particularly in the calling accuracy of minor alleles, which is the principal
      concern for rare and low-frequency variants. The application of zCall to post
      process the output from iCall also produced marginally improved performance to
      the combination of zCall and GenCall. AVAILABILITY AND IMPLEMENTATION: iCall is
      implemented in C++ for use on Linux operating systems and is available for
      download at http://www.statgen.nus.edu.sg/~software/icall.html.

PMID- 24567546
TI  - Renal circadian clock regulates the dosing-time dependency of cisplatin-induced
      nephrotoxicity in mice.
AB  - Cisplatin, cis-diamminedichloro-platinum (CDDP), is a widely used anticancer
      agent, the clinical applications of which have been limited by severe
      nephrotoxicity. Although dosing time-dependent differences in CDDP-induced
      nephrotoxicity have been reported in both humans and laboratory animals, the
      underlying mechanism remains unknown. In the present study, we investigated the
      molecular mechanism for the dosing-time dependency of the nephrotoxic effect of
      CDDP in mice. CDDP-induced nephrotoxicity was significantly attenuated by
      injecting CDDP at times of the day when its renal clearance was enhanced. The
      dosing-time dependency of the nephrotoxic effect was parallel to that of CDDP
      incorporation into renal DNA. Two types of transporters, organic cation
      transporter 2 (OCT2, encoded by Slc22a2) and multidrug and toxin extrusion 1
      (MATE1, encoded by Slc47a1), are responsible for the renal excretion of CDDP. The
      expression of OCT2, but not MATE1, exhibited a significant time-dependent
      oscillation in the kidneys of mice. The circadian expression of OCT2 was closely
      related to the dosing-time dependency of CDDP incorporation into renal DNA.
      Molecular components of the circadian clock regulated the renal expression of
      Slc22a2 mRNA by mediating peroxisome proliferator-activated receptor-alpha, which
      resulted in rhythmic oscillations in OCT2 protein levels. These findings indicate
      a clock-regulated mechanism of dosing time-dependent changes in CDDP-induced
      nephrotoxicity and also suggest a molecular link between the circadian clock and
      renal xenobiotic excretion. 

PMID- 24567548
TI  - Editor's briefing.

PMID- 24567549
TI  - Dealing with family history of breast cancer: something new, something old.

PMID- 24567547
TI  - Quaternary arrangement of an active, native group II intron ribonucleoprotein
      complex revealed by small-angle X-ray scattering.
AB  - The stable ribonucleoprotein (RNP) complex formed between the Lactococcus lactis
      group II intron and its self-encoded LtrA protein is essential for the intron's
      genetic mobility. In this study, we report the biochemical, compositional,
      hydrodynamic and structural properties of active group II intron RNP particles
      (+A) isolated from its native host using a novel purification scheme. We employed
      small-angle X-ray scattering to determine the structural properties of these
      particles as they exist in solution. Using sucrose as a contrasting agent, we
      derived a two-phase quaternary model of the protein-RNA complex. This approach
      revealed that the spatial properties of the complex are largely defined by the
      RNA component, with the protein dimer located near the center of mass. A transfer
      RNA fusion engineered into domain II of the intron provided a distinct landmark
      consistent with this interpretation. Comparison of the derived +A RNP shape with
      that of the previously reported precursor intron (DeltaA) particle extends
      previous findings that the loosely packed precursor RNP undergoes a dramatic
      conformational change as it compacts into its active form. Our results provide
      insights into the quaternary arrangement of these RNP complexes in solution, an
      important step to understanding the transition of the group II intron from the
      precursor to a species fully active for DNA invasion. 

PMID- 24567550
TI  - Vitamin D: too much of a good thing?

PMID- 24567551
TI  - Confronting child obesity in primary care.

PMID- 24567552
TI  - Exercise prescription: what does it mean for primary care?

PMID- 24567553
TI  - Diagnostic biopsy of melanoma: primary or secondary care?

PMID- 24567554
TI  - Authors' response.

PMID- 24567555
TI  - The future of elderly care in Turkey.

PMID- 24567557
TI  - Improving out-of-hours handovers.

PMID- 24567556
TI  - Why all GPs should be bothered about Billy.

PMID- 24567559
TI  - Anal fissures; first do no harm.

PMID- 24567558
TI  - Tackling the alcohol issue in France.

PMID- 24567561
TI  - Rebel with a cause: when morals, politics, and religion collide.

PMID- 24567562
TI  - Partnership in general practice: what chance a future?

PMID- 24567563
TI  - Munch's visions from within the eye.

PMID- 24567569
TI  - The science of opera with Stephen Fry and Alan Davies.

PMID- 24567570
TI  - Self-service.

PMID- 24567571
TI  - Breast is best: just maybe in private?

PMID- 24567572
TI  - GP induction and refresher and retainer schemes: are they cost-effective?

PMID- 24567573
TI  - A practical approach for UK primary care on the management of cow's milk allergy
      in infants.

PMID- 24567574
TI  - Assessment and treatment for people with fertility problems: NICE guideline.

PMID- 24567575
TI  - Tips for GP trainees working in family planning.

PMID- 24567576
TI  - Use of alarm features in referral of febrile children to the emergency
      department: an observational study.
AB  - BACKGROUND: The diagnostic value of alarm features of serious infections in low
      prevalence settings is unclear. AIM: To explore to what extent alarm features
      play a role in referral to the emergency department (ED) by GPs who face a
      febrile child during out-of-hours care. DESIGN AND SETTING: Observational study
      using semi-structured, routine clinical practice data of febrile children (<16
      years) presenting to GP out-of-hours care. METHOD: Logistic regression analyses
      were performed to assess the association between alarm features of serious
      infections (selected from two guidelines and one systematic review) and referral
      to the ED. Adherence to the guideline was explored by a 2*2 contingency table.
      RESULTS: In total 794 (8.1%) of 9794 eligible patients were referred to the ED.
      Alarm signs most strongly associated with referral were 'age <1 month',
      'decreased consciousness', 'meningeal irritation', and 'signs of dehydration'.
      Nineteen percent of 3424 children with a positive referral indication according
      to the guideline were referred to the ED. The majority of those not referred had
      only one or two alarm features present. A negative referral indication was
      adhered to for the majority of children. Still, in 20% of referred children,
      alarm features were absent. CONCLUSION: In contrast to guidance, GPs working in
      primary out-of-hours care seem more conservative in referring febrile children to
      the ED, especially if only one or two alarm features of serious infection are
      present. In addition, in 20% of referred children, alarm features were absent,
      which suggests that other factors may be important in decisions about referral of
      febrile children to the hospital ED.

PMID- 24567577
TI  - Parents' knowledge, attitudes, and practice in childhood fever: an internet-based
      survey.
AB  - BACKGROUND: Fever in children is common and mostly caused by self-limiting
      infections. However, the number of (re)consultations in primary care is high,
      driven by lack of knowledge and fear among parents. These drivers have only been
      studied in parents when consulting with their sick child. AIM: To study
      knowledge, attitudes, and practice in childhood fever in parents within the
      general population. DESIGN AND SETTING: Internet-based survey of a sample of 1000
      parents from the general population of the Netherlands. METHOD: A 26-item cross
      sectional survey was conducted of parents with one or more children aged < 5
      years. RESULTS: Of 625 responders (average age 34.9 years), 63.4% and 43.7%
      indicated ever visiting their GP or GP's out-of-hours centre with a febrile
      child, respectively: 88.3% knew the definition of fever (>38 degrees C), 55.2%
      correctly stated that antibiotics are effective in treating bacterial infections
      and not viral infections, and 72.0% knew that not every child with a fever needs
      treatment with antibiotics or paracetamol. When asked to prioritise aspects of a
      GP's consultation, 53.6% considered physical examination as most important.
      Obtaining a prescription for antibiotics or antipyretics was considered least
      important. CONCLUSION: Knowledge, attitudes, and practices concerning childhood
      fever varied among parents with young children. Parents generally expect thorough
      physical examination and information, but not a prescription for medication
      (antibiotics or antipyretics) when consulting with a feverish child. GPs must be
      aware of these expectations as these provide opportunities to enhance
      consultations in general and prescription strategies in particular.

PMID- 24567578
TI  - Diabetes screening after gestational diabetes in England: a quantitative
      retrospective cohort study.
AB  - BACKGROUND: The National Institute for Health and Care Excellence (NICE)
      recommends postpartum and annual monitoring for diabetes for females who have had
      a diagnosis of gestational diabetes mellitus (GDM). AIM: To describe the current
      state of follow-up after GDM in primary care, in England. DESIGN AND SETTING: A
      retrospective cohort study in 127 primary care practices. The total population
      analysed comprised 473 772 females, of whom 2016 had a diagnosis of GDM. METHOD:
      Two subgroups of females were analysed using electronic general practice records.
      In the first group of females (n = 788) the quality of postpartum follow-up was
      assessed during a 6-month period. The quality of long-term annual follow-up was
      assessed in a second group of females (n = 718), over a 5-year period. The two
      outcome measures were blood glucose testing performed within 6 months postpartum
      (first group) and blood glucose testing performed annually (second group).
      RESULTS: Postpartum follow-up was performed in 146 (18.5%) females within 6
      months of delivery. Annual rates of long-term follow-up stayed consistently
      around 20% a year. Publication of the Diabetes in Pregnancy NICE guidelines, in
      2008, had no effect on long-term screening rates. Substantial regional
      differences were identified among rates of follow-up. CONCLUSION: Monitoring of
      females after GDM is markedly suboptimal despite current recommendations.

PMID- 24567579
TI  - Management of suspected infectious diarrhoea by English GPs: are they right?
AB  - BACKGROUND: The criteria used when GPs submit stool specimens for microbiological
      investigation are unknown. AIM: To determine what criteria GPs use to send stool
      specimens, and if they are consistent with national guidance, and whether GPs
      would prescribe an antibiotic before they receive a result. DESIGN AND SETTING:
      Questionnaire survey of 974 GPs in 172 surgeries in England. METHOD: GPs were
      sent a questionnaire (23 questions) based on national guidance. RESULTS:
      Questionnaires were returned by 90% (154/172) of surgeries and 49% (477/968) of
      GPs. GPs reported sending stool specimens in about 50% of cases of suspected
      infectious diarrhoea, most commonly because of individual symptoms, rather than
      public health implications. Fewer considered sampling with antibiotic-associated
      diarrhoea post hospitalisation, or children with acute, painful, bloody
      diarrhoea; only 14% mentioned outbreaks as a reason. Nearly one-half of GPs
      reported they would consider antibiotics in suspected cases of Escherichia coli
      O157, which is contraindicated. Only 23% of GPs would send the recommended three
      specimens for ova, cysts, and parasites (OCP) examination. Although 89% of GPs
      gave some verbal advice on how to collect stool specimens, only 2% of GPs gave
      patients any written instructions. CONCLUSION: GPs need more education to address
      gaps in knowledge about the risks and diagnosis of different infections in
      suspected infectious diarrhoea, especially Clostridium difficile post
      antibiotics, E. coli O157, and requesting OCPs. Advice on reports, tick boxes, or
      links to guidance on electronic request forms may facilitate this.

PMID- 24567580
TI  - Detecting recurrent major depressive disorder within primary care rapidly and
      reliably using short questionnaire measures.
AB  - BACKGROUND: Major depressive disorder (MDD) is often a chronic disorder with
      relapses usually detected and managed in primary care using a validated
      depression symptom questionnaire. However, for individuals with recurrent
      depression the choice of which questionnaire to use and whether a shorter measure
      could suffice is not established. AIM: To compare the nine-item Patient Health
      Questionnaire (PHQ-9), the Beck Depression Inventory, and the Hospital Anxiety
      and Depression Scale against shorter PHQ-derived measures for detecting episodes
      of DSM-IV major depression in primary care patients with recurrent MDD. DESIGN
      AND SETTING: Diagnostic accuracy study of adults with recurrent depression in
      primary care predominantly from Wales METHOD: Scores on each of the depression
      questionnaire measures were compared with the results of a semi-structured
      clinical diagnostic interview using Receiver Operating Characteristic curve
      analysis for 337 adults with recurrent MDD. RESULTS: Concurrent questionnaire and
      interview data were available for 272 participants. The one-month prevalence rate
      of depression was 22.2%. The area under the curve (AUC) and positive predictive
      value (PPV) at the derived optimal cut-off value for the three longer
      questionnaires were comparable (AUC = 0.86-0.90, PPV = 49.4-58.4%) but the AUC
      for the PHQ-9 was significantly greater than for the PHQ-2. However, by
      supplementing the PHQ-2 score with items on problems concentrating and feeling
      slowed down or restless, the AUC (0.91) and the PPV (55.3%) were comparable with
      those for the PHQ-9. CONCLUSION: A novel four-item PHQ-based questionnaire
      measure of depression performs equivalently to three longer depression
      questionnaires in identifying depression relapse in patients with recurrent MDD.

PMID- 24567581
TI  - Missed opportunities in prevention of cardiovascular disease in primary care: a
      cross-sectional study.
AB  - BACKGROUND: Screening cardiovascular disease (CVD) risk is an important part of
      CVD prevention. The success of screening is dependent on the rigour with which
      treatments are subsequently prescribed. AIM To establish the extent to which
      treatment conforms to guidelines. DESIGN AND SETTING: Cross-sectional study of
      anonymised patient records from 19 general practices in the UK. METHOD: Data
      relating to patient characteristics, including CVD risk factors, risk score and
      prescribed medication were extracted. CVD risk (thus eligibility for cholesterol
      and blood pressure-lowering treatment) was calculated using the Framingham
      equation. Guideline adherence was defined with descriptive statistics and
      comparisons by age, sex and disease were made using chi(2) tests. RESULTS: Of the
      34 975 patients (aged 40-74 years) included in this study, 2550 (7%) patients had
      existing CVD and 12 349 (35%) had a calculable CVD risk or were on treatment. CVD
      risk was formally assessed in 8390 (24%) patients. Approximately 7929 (64%)
      patients eligible for primary prevention therapy were being treated appropriately
      for their CVD risk. Guideline adherence was higher in younger patients (6284
      [69%] aged 40-64 years versus 1645 [50%] aged 65-74 years, P<0.001) and in
      females (4334 [69%] females versus 3595 [59%] males, P<0.001). There was no
      difference in guideline adherence between patients where CVD risk had been
      recorded and those where CVD was calculable. Guideline adherence in patients with
      existing CVD was highest in patients with ischaemic heart disease (866 [ischaemic
      heart disease], 52%, versus 288 [stroke], 46%, versus 276 [other CVD], 39%;
      P<0.001). CONCLUSION: There is scope for improvement in assessment and treatment
      for prevention of CVD in clinical practice. Increasing the uptake of evidence
      based treatments would improve the cost-effectiveness of CVD risk screening
      programmes.

PMID- 24567582
TI  - Effectiveness of general practice-based health checks: a systematic review and
      meta-analysis.
AB  - BACKGROUND: A recent review concluded that general health checks fail to reduce
      mortality in adults. AIM: This review focuses on general practice-based health
      checks and their effects on both surrogate and final outcomes. DESIGN AND
      SETTING: Systematic search of PubMed, Embase, and the Cochrane Central Register
      of Controlled Trials. METHOD: Relevant data were extracted from randomised trials
      comparing the health outcomes of general practice-based health checks versus
      usual care in middle-aged populations. RESULTS: Six trials were included. The end
      point differences between the intervention and control arms in total cholesterol
      (TC), systolic and diastolic blood pressure (SBP, DBP), and body mass index (BMI)
      were -0.13 mmol/l (95% confidence interval [CI] = -0.19 to -0.07), -3.65 mmHg
      (95% CI = -6.50 to -0.81), -1.79 mmHg (95% CI = -2.93 to -0.64), and -0.45
      kg/m(2) (95% CI = -0.66 to -0.24), respectively. The odds of a patient remaining
      at 'high risk' with elevated TC, SBP, DBP, BMI or continuing smoking were 0.63
      (95% CI = 0.50 to 0.79), 0.59 (95% CI = 0.28 to 1.23), 0.63 (95% CI = 0.53 to
      0.74), 0.89 (95% CI = 0.81 to 0.98), and 0.91 (95% CI = 0.82 to 1.02),
      respectively. There was little evidence of a difference in total mortality (OR
      1.03, 95% CI = 0.90 to 1.18). Higher CVD mortality was observed in the
      intervention group (OR 1.30, 95% CI = 1.02 to 1.66). CONCLUSION: General practice
      based health checks are associated with statistically significant, albeit
      clinically small, improvements in surrogate outcome control, especially among
      high-risk patients. Most studies were not originally designed to assess
      mortality.

PMID- 24567583
TI  - Increasing the QOF upper payment threshold in general practices in England:
      impact of implementing government proposals.
AB  - BACKGROUND: General practices in the UK receive incentive payments for managing
      patients with selected chronic conditions under the Quality and Outcomes
      Framework (QOF) scheme. Payments are made when a negotiated threshold percentage
      of patients receive the appropriate intervention. AIM: From 2013-2014 in England
      the Department of Health has proposed that this negotiated threshold is replaced
      with a value equal to the 75th percentile of national performance to attract
      maximum payments. This is an investigation of the potential impact of this change
      on practice income and workload. DESIGN AND SETTING: Analysis of 2011-2012 QOF
      dataset (the latest available) which covers 8123 GP practices and 55.5 million
      patients in England. METHOD: The 75th percentile of performance was calculated
      for 52 clinical indicators and applied to 2011-2012 performance. Estimations were
      made of financial and workload impacts on practices, and whether practices with
      different characteristics would be disproportionately affected. RESULTS: The
      proposed changes will result in an increase in the upper payment threshold of
      each clinical indicator by a mean of 7.47% (range 2.16-38.87%). If performance
      remains static practices would lose a mean of 47.68 (0-108.33) QOF points,
      equivalent to a mean financial change of -L279.60 (-L35 352.50 to +L19 957.78)
      per practice for these 52 indicators. CONCLUSION: Increasing the QOF upper
      payment threshold to the 75th percentile of national performance will, if
      clinical performance remains static, substantially reduce the mean number of QOF
      points achieved per practice. However, this translates into only a small mean
      loss of income per practice.

PMID- 24567585
TI  - Can 88% of patients with acute lower respiratory infection all be special?

PMID- 24567586
TI  - The future shape of primary care.

PMID- 24567587
TI  - Ecological studies: use with caution.

PMID- 24567588
TI  - Cauda equina syndrome: implications for primary care.

PMID- 24567589
TI  - The future of general practice in South Africa.

PMID- 24567590
TI  - Suicide risk among farming patients and the effects of HS2.

PMID- 24567591
TI  - Will the age of austerity save the NHS?

PMID- 24567592
TI  - Reducing inappropriate A&E attendances.

PMID- 24567593
TI  - Studying and reducing DNAs to improve access.

PMID- 24567594
TI  - Predictive validity of selection for entry into postgraduate training in general
      practice.

PMID- 24567595
TI  - Why study?

PMID- 24567596
TI  - GPs' job satisfaction: doctors who chose general practice early or late.

PMID- 24567597
TI  - Are GP career intentions more prevalent in UCL Primary Health Care iBSc students?

PMID- 24567598
TI  - Text messaging to promote health.

PMID- 24567599
TI  - Social media in general practice: a ray of hope or a can of worms?

PMID- 24567600
TI  - Private health care and empathy.

PMID- 24567601
TI  - Learning from ward number six.

PMID- 24567602
TI  - 20 years of GPnotebook: from a medical student project to a national resource.

PMID- 24567603
TI  - Poems in practice.

PMID- 24567604
TI  - Reflections on the plight of Syrian refugees in Lebanon.

PMID- 24567605
TI  - An A-Z of medical philosophy.

PMID- 24567606
TI  - Money, media, and general practice.

PMID- 24567607
TI  - Personal genotyping and general practice.

PMID- 24567610
TI  - Secrets and magic.

PMID- 24567611
TI  - Narrowing the health inequality gap by annual health checks for patients with
      intellectual disability.

PMID- 24567612
TI  - Oral health: a neglected area of routine diabetes care?

PMID- 24567613
TI  - Very late perforation of an implantable cardioverter defibrillator lead: a case
      report.

PMID- 24567614
TI  - Tips for GP trainees working in vascular surgery.

PMID- 24567615
TI  - Detection of heart disease by open access echocardiography: a retrospective
      analysis of general practice referrals.
AB  - BACKGROUND: Heart disease is difficult to detect clinically and it has been
      suggested that echocardiography should be available to all patients with possible
      cardiac symptoms or signs. AIM: To analyse the results of 2 years of open access
      echocardiography for the frequency of structural heart disease according to
      request. DESIGN AND SETTING: Retrospective database analysis in a teaching
      hospital open access echocardiography service. METHOD: Reports of all open access
      transthoracic echocardiograms between January 2011 and December 2012 were
      categorised as normal, having minor abnormalities, or significant abnormalities
      according to the indication. RESULTS: There were 2343 open access echocardiograms
      performed and there were significant abnormalities in 29%, predominantly valve
      disease (n = 304, 13%), LV systolic dysfunction (n = 179, 8%), aortic dilatation
      (n = 80, 3%), or pulmonary hypertension (n = 91, 4%). If echocardiography had
      been targeted at a high-risk group, 267 with valve disease would have been
      detected (compared to 127 with murmur alone) and 139 with LV systolic dysfunction
      (compared to 91 with suspected heart failure alone). Most GP practices requested
      fewer than 10 studies, but 6 practices requested over 70 studies. CONCLUSION:
      Open access echocardiograms are often abnormal but structural disease may not be
      suspected from the clinical request. Uptake by individual practices is patchy. A
      targeted expansion of echocardiography in patients with a high likelihood of
      disease is therefore likely to increase the detection of clinically important
      pathology.

PMID- 24567616
TI  - GPs' management strategies for patients with insomnia: a survey and qualitative
      interview study.
AB  - BACKGROUND: Patients frequently experience sleep problems and present to primary
      care. However, information is limited regarding the management strategies that
      GPs employ. AIM: To gain an understanding of current GP management strategies for
      insomnia. DESIGN AND SETTING: A postal questionnaire survey and qualitative
      interviews with GPs in the south of England. METHOD: A postal survey of 296 GPs
      and qualitative interviews were carried out with 23 of the GPs. RESULTS: The
      survey response rate was 56% (166/296). GPs look for signs of depression and
      anxiety in patients and if present treat these first. 'Sleep hygiene' advice is
      provided by 88% (147/166) of GPs but often seems insufficient and they feel under
      pressure to prescribe. Benzodiazepines and Z drugs are prescribed, often
      reluctantly, for short periods, because of known problems with dependence and
      tolerance. Many GPs prescribe low-dose amitriptyline for insomnia although it is
      not licensed for this indication. For insomnia 95% (157/166) of survey responders
      'ever prescribe' amitriptyline, with 31% (52/166) stating they do so commonly.
      Most GPs perceived amitriptyline to be effective and a longer-term option for
      those with ongoing sleep problems. GPs report a lack of knowledge and confidence
      in the provision and use of psychological therapies, such as cognitive
      behavioural therapy (CBT), in the management of insomnia. CONCLUSION: GPs often
      find 'sleep hygiene' advice is insufficient for managing insomnia and report
      frequently prescribing medication, including amitriptyline (off licence), which
      is often based on perceived patient pressure for a prescription. Patients are
      rarely offered psychological therapies such as CBT for insomnia, despite evidence
      suggesting its potential effectiveness.

PMID- 24567617
TI  - Testing for thrombophilia: clinical update.

PMID- 24567618
TI  - Public attitudes towards opt-out testing for HIV in primary care: a qualitative
      study.
AB  - BACKGROUND; The rate of new HIV infections in the UK continues to rise, with one
      quarter of cases undiagnosed. Opt-out HIV testing - in which tests are routinely
      offered to all patients, with the offer to decline - have proved effective in
      antenatal care. Pilot studies of HIV opt-out testing at GP registration and acute
      medical admission to hospital have described service-level issues and the
      clinician's perspective, but not the views of the general public. AIM: To further
      understand the public's perspective on opt-out testing for HIV in England. DESIGN
      AND SETTING: Focus groups (n = 9) with a total of 54 participants in Brighton,
      England, where HIV prevalence is high. METHOD: Quota sampling on sexual
      orientation, age, sex, and testing experience was applied to groups with high and
      low HIV prevalences, and analysed using framework analysis. RESULTS: Opt-out
      testing for HIV was acceptable. Testing on GP registration was regarded as a more
      appropriate setting than acute medical admission. Participants from groups in
      which HIV has a higher prevalence felt HIV testing required consideration that
      may not be possible during acute hospital admission. However, there was concern
      that screening would still be targeted at groups in which HIV prevalence is
      higher, based on clinicians' judgement of patients' behaviours, sexuality, or
      ethnicity. CONCLUSION: The opt-out method of testing for HIV must be routinely
      offered to all who are eligible, to increase test uptake and to prevent
      communities feeling targeted. Any pressure to test is likely to be poorly
      received. Inaccurate concerns about medical records being shared with financial
      services are a disincentive to test. Primary care should be an active setting for
      opt-out HIV testing.

PMID- 24567619
TI  - Case-finding for hepatitis C in primary care: a mixed-methods service evaluation.
AB  - BACKGROUND: Hepatitis C is often asymptomatic, presenting with liver failure and
      cancer decades after infection. People who inject drugs (PWID) and immigrant
      populations from countries with a moderate-to-high prevalence of hepatitis C
      virus (HCV) are the main risk groups. Deaths and hospital admissions due to HCV
      cirrhosis tripled between 1998 and 2010, but the majority of people with chronic
      HCV are unaware of it. AIM: To identify patients at risk of developing hepatitis
      C using routine GP data, to determine the proportion not tested, and to explore
      GPs' views regarding testing. DESIGN AND SETTING: Mixed-methods service
      evaluation (density-based selection of PWID) in six NHS practices in Bristol.
      METHOD: Patients at risk of HCV were identified. The Health Protection Agency
      laboratory (now part of Public Health England) provided test results. Semi
      structured interviews with 17 GPs were audiorecorded and thematic analyses
      conducted on anonymised transcripts. RESULTS: Of 3765 patients identified as
      being at risk of developing hepatitis C, 3051 (81%) had no test result, including
      53% of PWID and 93% of the 'ethnicity' group. All GPs said they usually test
      PWID. Most GPs test for HIV and hepatitis B in immigrants more often than they
      test for HCV. Barriers to testing included not questioning patients about risk
      factors, competing priorities, the chaotic lifestyle of PWID, difficulty
      extracting information from computerised records, and forgetting to address HCV.
      CONCLUSION: Computer prompts and GP education on whom to test are warranted.
      Ensuring that country of origin and drug use is included on the new-patient
      questionnaire might also aid case-finding for HCV.

PMID- 24567620
TI  - Amoxicillin for acute lower respiratory tract infection in primary care: subgroup
      analysis of potential high-risk groups.
AB  - BACKGROUND: Antibiotics are of limited overall clinical benefit for uncomplicated
      lower respiratory tract infection (LRTI) but there is uncertainty about their
      effectiveness for patients with features associated with higher levels of
      antibiotic prescribing. AIM: To estimate the benefits and harms of antibiotics
      for acute LRTI among those producing coloured sputum, smokers, those with fever
      or prior comorbidities, and longer duration of prior illness. DESIGN AND SETTING:
      Secondary analysis of a randomised controlled trial of antibiotic placebo for
      acute LRTI in primary care. METHOD: Two thousand and sixty-one adults with acute
      LRTI, where pneumonia was not suspected clinically, were given amoxicillin or
      matching placebo. The duration of symptoms, rated moderately bad or worse
      (primary outcome), symptom severity on days 2-4 (0-6 scale), and the development
      of new or worsening symptoms were analysed in pre-specified subgroups of
      interest. Evidence of differential treatment effectiveness was assessed in
      prespecified subgroups by interaction terms. RESULTS: No subgroups were
      identified that were significantly more likely to benefit from antibiotics in
      terms of symptom duration or the development of new or worsening symptoms. Those
      with a history of significant comorbidities experienced a significantly greater
      reduction in symptom severity between days 2 and 4 (interaction term -0.28, P =
      0.003; estimated effect of antibiotics among those with a past history -0.28 [95%
      confidence interval = -0.44 to -0.11], P = 0.001), equivalent to three people in
      10 rating symptoms as a slight rather than a moderately bad problem. For
      subgroups not specified in advance antibiotics provided a modest reduction in
      symptom severity for non-smokers and for those with short prior illness duration
      (<7 days), and a modest reduction in symptom duration for those with short prior
      illness duration. CONCLUSION: There is no clear evidence of clinically meaningful
      benefit from antibiotics in the studied high-risk groups of patients presenting
      in general practice with uncomplicated LRTIs where prescribing is highest. Any
      possible benefit must be balanced against the side-effects and longer-term
      effects on antibiotic resistance.

PMID- 24567621
TI  - Medication use in European primary care patients with lower respiratory tract
      infection: an observational study.
AB  - BACKGROUND It is largely unknown what medication is used by patients with lower
      respiratory tract infection (LRTI). AIM To describe the use of self-medication
      and prescribed medication in adults presenting with LRTI in different European
      countries, and to relate self-medication to patient characteristics. DESIGN AND
      SETTING An observational study in 16 primary care networks in 12 European
      countries. METHOD A total of 2530 adult patients presenting with LRTI in 12
      European countries filled in a diary on any medication used before and after a
      primary care consultation. Patient characteristics related to self-medication
      were determined by univariable and multivariable logistic regression analysis.
      RESULTS The frequency and types of medication used differed greatly between
      European countries. Overall, 55.4% self-medicated before consultation, and 21.5%
      after consultation, most frequently with paracetamol, antitussives, and
      mucolytics. Females, non-smokers, and patients with more severe symptoms used
      more self-medication. Patients who were not prescribed medication during the
      consultation self-medicated more often afterwards. Self-medication with
      antibiotics was relatively rare. CONCLUSION A considerable amount of medication,
      often with no proven efficacy, was used by adults presenting with LRTI in primary
      care. There were large differences between European countries. These findings
      should help develop patient information resources, international guidelines, and
      international legislation concerning the availability of over-the-counter
      medication, and can also support interventions against unwarranted variations in
      care. In addition, further research on the effects of symptomatic medication is
      needed. 

PMID- 24567622
TI  - Quality deviations in cancer diagnosis: prevalence and time to diagnosis in
      general practice.
AB  - BACKGROUND: High quality in every phase of cancer diagnosis is important to
      optimise the prognosis for the patient. General practice plays an important role
      in this phase. AIM: The aim was to describe the prevalence and the types of
      quality deviations (QDs) that arise during the diagnostic pathway in general
      practice as assessed by GPs and to analyse the association between these QDs, the
      cancer type, and the GP's interpretation of presenting symptoms as well as the
      influence on the diagnostic interval. DESIGN AND SETTING: A Danish retrospective
      cohort study based on questionnaire data from 1466 GPs on 5711 incident patients
      with cancer identified in the Danish National Patient Registry (response rate =
      71.4%). The GP was involved in diagnosing in 4036 cases. METHOD: Predefined QDs
      were prompted with the possibility for free text. QD prevalence was estimated as
      was the association between QDs and diagnosis, the GP's symptom interpretation,
      and time to diagnosis. RESULTS: QDs were present for 30.4% (95% confidence
      interval [CI] = 29.0 to 31.9) of cancer patients. The most prevalent QD was
      'retrospectively, one or more of my clinical decisions were less optimal'. QDs
      were most prevalent among patients with vague symptoms (24.1% for alarm symptoms
      versus 39.5% for vague symptoms [P<0.001]). QD presence implied a 41-day (95% CI
      = 38.4 to 43.6) longer median diagnostic interval. CONCLUSION: GPs noted at least
      one QD, which often involved clinical decisions, for one-third of all cancer
      patients. QDs were more likely among patients with vague symptoms and increased
      the diagnostic interval considerably.

PMID- 24567624
TI  - Editor's briefing.

PMID- 24567625
TI  - Time to get Mediterranean with our dietary advice.

PMID- 24567623
TI  - Why do patients with cancer access out-of-hours primary care? A retrospective
      study.
AB  - BACKGROUND: Identifying why patients with cancer seek out-of-hours (OOH) primary
      medical care could highlight potential gaps in anticipatory cancer care. AIM: To
      explore the reasons for contact and the range and prevalence of presenting
      symptoms in patients with established cancer who presented to a primary care OOH
      department. DESIGN AND SETTING: A retrospective review of 950 anonymous case
      records for patients with cancer who contacted the OOH general practice service
      in Grampian, Scotland between 1 January 2010 and 31 December 2011. METHOD:
      Subjects were identified by filtering the OOH computer database using the Read
      Codes 'neoplasm', 'terminal care', and 'terminal illness'. Consultations by
      patients without cancer and repeated consultations by the same patient were
      excluded. Data were anonymised. Case records were read independently by two
      authors who determined the presenting symptom(s). RESULTS: Anonymous case records
      were reviewed for 950 individuals. Eight hundred and fifty-two patients made
      contact because of a symptom. The remaining 97 were mostly administrative and
      data were missing for one patient. The most frequent symptoms were pain (n =
      262/852, 30.8%); nausea/vomiting (n = 102/852, 12.0%); agitation (n = 53/852,
      6.2%); breathlessness (n = 51/852, 6.0%); and fatigue (n = 48/852, 5.6%). Of the
      262 patients who presented with pain, at least 127 (48.5%) had metastatic disease
      and 141 (53.8%) were already prescribed strong opiate medication. CONCLUSION:
      Almost one-third of patients with cancer seeking OOH primary medical care did so
      because of poorly controlled pain. Pain management should specifically be
      addressed during routine anticipatory care planning.

PMID- 24567626
TI  - The microbiome: what it means for medicine.

PMID- 24567627
TI  - Heartburn, Barrett's oesophagus and cancer: implications for primary care.

PMID- 24567628
TI  - Acute medicine and general practice: a key interface in managing emergency care
      pressures.

PMID- 24567630
TI  - Proceed with caution: authors' response.

PMID- 24567631
TI  - We need another word for 'chronic'.

PMID- 24567629
TI  - Vitamin D testing: three important issues.

PMID- 24567632
TI  - Primary care patients' reasons for choosing emergency department services in
      Jordan.

PMID- 24567633
TI  - Self management: what happens to people with long-term conditions in between NHS
      appointments?

PMID- 24567634
TI  - Improved support required to increase breastfeeding rates.

PMID- 24567636
TI  - A lasting legacy: clinical commissioning groups and sport medicine.

PMID- 24567637
TI  - Language is not just data.

PMID- 24567638
TI  - Unusual chest radiograph finding plombs old depths.

PMID- 24567639
TI  - An A-Z of medical philosophy: O is for ontology.

PMID- 24567640
TI  - Medicine: are we not a muse?

PMID- 24567646
TI  - Nudging towards the exit.

PMID- 24567647
TI  - Five cards: a simple guide to beginning the consultation.

PMID- 24567648
TI  - Video capsule endoscopy for the investigation of the small bowel: primary care
      diagnostic technology update.

PMID- 24567649
TI  - Tips for GP trainees working in colorectal surgery.

PMID- 24567650
TI  - Prevalence of comorbid depression and obesity in general practice: a cross
      sectional survey.
AB  - BACKGROUND: General practice is a common setting for the provision of weight
      management advice, as well as the treatment of depression. While there is some
      evidence of a reciprocal relationship between obesity and depression, there are
      limited data about the rates of depression among general practice patients who
      are underweight, normal weight, overweight, and obese. AIM To explore the
      prevalence of depression among underweight, normal weight, overweight, and obese
      general practice patients. DESIGN AND SETTING: A cross-sectional survey was
      conducted in 12 Australian general practices. METHOD Patients aged >=18 years and
      older who were presenting for general practice care were eligible to participate.
      Consenting patients completed a touchscreen computer survey assessing self
      reported weight and height. Depression was assessed by the Patient Health
      Questionnaire-9 (PHQ-9), with a score of >=10 used to indicate possible
      depression. RESULTS: Data were obtained from 3361 participants. The prevalence of
      depression was 24% (95% confidence interval [CI] = 11.86 to 39.28) among
      underweight participants, 11% (95% CI = 8.5 to 14.0) among normal weight
      participants, 12% (95% CI = 0.9 to 15.2) among overweight participants, and 23%
      (95% CI = 17.8 to 29.0) among obese participants. The prevalence of depression
      was higher for women than for men across all weight categories except
      underweight. CONCLUSION: Weight and depression demonstrated a U-shaped
      relationship, with higher prevalence of depression observed among underweight and
      obese general practice patients. These conditions may act as red flags for
      opportunistic screening of depression in the general practice setting.

PMID- 24567651
TI  - Which weight-loss programmes are as effective as Weight Watchers(R)?: non
      inferiority analysis.
AB  - BACKGROUND: Three randomised controlled trials have provided strong evidence that
      Weight Watchers((r)) is an effective weight-loss programme but there is
      insufficient evidence to determine whether three other weight-loss programmes are
      also effective. AIM: To examine whether other group-based weight-loss programmes
      were not inferior to Weight Watchers. DESIGN AND SETTING: A prospective cohort
      study using a non-inferiority analysis of 3290 adults referred through primary
      care. METHOD Participants who met the eligibility criteria for primary care
      obesity management treatment chose a free programme (Weight Watchers, Rosemary
      Conley Diet and Fitness Clubs, Slimming World or a NHS group programme) lasting 3
      months; they were weighed at 3 months (programme end) and self-reported their
      weight at 12 months. RESULTS: At 3 months, weight loss achieved through Rosemary
      Conley and Slimming World was not inferior to Weight Watchers. The NHS group
      programme was inferior. At 12 months Slimming World and Rosemary Conley were not
      inferior to Weight Watchers, although participants using Slimming World lost
      significantly more weight than those using Weight Watchers. Data on the NHS group
      programme were inconclusive. CONCLUSION: In the short term all commercial weight
      loss programmes appear to result in similar weight loss but the NHS alternative
      appears to produce less weight loss. At 12 months Slimming World led to greater
      weight loss but the differences between commercial programmes was small and of
      minor clinical importance.

PMID- 24567652
TI  - Factors associated with prevalence and types of 'may be fit' advice on fit notes:
      a cross-sectional primary care analysis.
AB  - BACKGROUND: The 'fit note', with the opportunity for the GP to advise that a
      patient 'may be fit' to do some work, was introduced in April 2010. AIM: To
      estimate numbers of fit notes with 'may be fit' advice, the types of advice, and
      factors associated with any inclusion of such advice in the fit note. DESIGN AND
      SETTING: Cross-sectional analysis of fit note data from 68 general practices in
      eight regions of England, Wales and Scotland. METHOD: Collection of practice fit
      note data via GP use of carbonised pads of fit notes for a period of 12 months.
      RESULTS: The 'may be fit' box was ticked on 5080 fit notes (6.4% of all fit notes
      in study). But there was a wide variation in completion rates across the 68
      practices (from 1% to 15%). The most prevalent individual item of advice was to
      'amend duties' of patient as a prerequisite for return to work (included in 42%
      of all notes containing any 'may be fit' advice). Advice was often incomplete or
      irrelevant, with some GPs failing to comply with official guidance. Inclusion of
      any 'may be fit' advice was independently associated with the patient being
      female, less socially deprived and having a physical health reason for receiving
      a fit note. CONCLUSION: Unlike other studies that have relied upon eliciting
      opinion, this study investigates how the fit note is being used in practice.
      Findings provide some evidence that the fit note is not yet being used to the
      optimum benefit of patients (and their employers).

PMID- 24567653
TI  - Sexual function in older women with pelvic floor symptoms: a cross-sectional
      study in general practice.
AB  - BACKGROUND: Pelvic floor symptoms are common and are negatively associated with
      sexual function which, in turn, is an important aspect of quality of life. The
      majority of older women with pelvic floor symptoms are treated in general
      practice but evidence from studies in general practice on the sexual functioning
      of these women is scarce. AIM: This study examined predictors of sexual
      inactivity in older women with pelvic floor symptoms in general practice and of
      sexual functioning in those women who are sexually active. DESIGN AND SETTING:
      Cross-sectional study in women (aged >=55 years) from 20 general practices who
      screened positive on a pelvic floor symptom questionnaire. METHOD: Logistic and
      linear regression analyses were used to determine predictors of sexual inactivity
      and sexual functioning (PISQ-12) by assessing their association with patient
      characteristics, symptoms (PFDI-20) and degree of prolapse (POP-Q). RESULTS: A
      total of 639 women were included (sexually active n = 393, sexually inactive n =
      246). Predictors of sexual inactivity were increasing age (odds ratio [OR] =
      1.13; 95% confidence interval [CI] = 1.10 to 1.17) and lower education (OR =
      2.31; 95% CI = 1.50 to 3.54; Nagelkerke R(2) = 0.208). In sexually active women,
      sexual functioning was associated with pelvic floor symptom distress (P<0.001)
      and pelvic floor surgery (P = 0.018; R(2) = 0.138). CONCLUSION: In older women
      with pelvic floor symptoms, increasing age and lower educational level are
      predictors of sexual inactivity. Many of these older women are sexually active
      and pelvic floor symptom distress is negatively associated with sexual
      functioning. These results may encourage GPs to ask about sexual problems in
      women with pelvic floor symptoms.

PMID- 24567654
TI  - Women's experiences of referral to a domestic violence advocate in UK primary
      care settings: a service-user collaborative study.
AB  - BACKGROUND: Women experiencing domestic violence and abuse (DVA) are more likely
      to be in touch with health services than any other agency, yet doctors and nurses
      rarely ask about abuse, often failing to identify signs of DVA in their patients.
      AIM: To understand women's experience of disclosure of DVA in primary care
      settings and subsequent referral to a DVA advocate in the context of a DVA
      training and support programme for primary care clinicians: Identification and
      Referral to Improve Safety (IRIS). DESIGN AND SETTING: A service-user
      collaborative study using a qualitative study design. Recruitment was from across
      IRIS trial settings in Bristol and Hackney, London. METHOD: Twelve women who had
      been referred to one of two specialist DVA advocates (based at specialist DVA
      agencies) were recruited by a GP taking part in IRIS. Women were interviewed by a
      survivor of DVA and interviews were recorded and transcribed verbatim. Analysis
      was thematic using constant comparison. RESULTS: GPs and nurses can play an
      important role in identifying women experiencing DVA and referring them to DVA
      specialist agencies. GPs may also have an important role to play in helping women
      maintain any changes they make as a result of referral to an advocate, by asking
      about DVA in subsequent consultations. CONCLUSION: A short time interval between
      a primary care referral and initial contact with an advocate was valued by some
      women. For the initial contact with an advocate to happen as soon as possible
      after a primary care referral has been made, a close working relationship between
      primary care and the third sector needs to be cultivated.

PMID- 24567655
TI  - Developing a preliminary 'never event' list for general practice using consensus
      building methods.
AB  - BACKGROUND: The 'never event' concept has been implemented in many acute hospital
      settings to help prevent serious patient safety incidents. Benefits include
      increasing awareness of highly important patient safety risks among the
      healthcare workforce, promoting proactive implementation of preventive measures,
      and facilitating incident reporting. AIM: To develop a preliminary list of never
      events for general practice. DESIGN AND SETTING: Application of a range of
      consensus-building methods in Scottish and UK general practices. METHOD: A total
      of 345 general practice team members suggested potential never events. Next,
      'informed' staff (n =15) developed criteria for defining never events and applied
      the criteria to create a list of candidate never events. Finally, UK primary care
      patient safety 'experts' (n = 17) reviewed, refined, and validated a preliminary
      list via a modified Delphi group and by completing a content validity index
      exercise. RESULTS: There were 721 written suggestions received as potential never
      events. Thematic categorisation reduced this to 38. Five criteria specific to
      general practice were developed and applied to produce 11 candidate never events.
      The expert group endorsed a preliminary list of 10 items with a content validity
      index (CVI) score of >80%. CONCLUSION: A preliminary list of never events was
      developed for general practice through practitioner experience and consensus
      building methods. This is an important first step to determine the potential
      value of the never event concept in this setting. It is now intended to undertake
      further testing of this preliminary list to assess its acceptability,
      feasibility, and potential usefulness as a safety improvement intervention.

PMID- 24567656
TI  - Patient experience and the role of postgraduate GP training: a cross-sectional
      analysis of national Patient Survey data in England.
AB  - BACKGROUND: Quality indicators for primary care focus predominantly on the public
      health model and organisational measures. Patient experience is an important
      dimension of quality. Accreditation for GP training practices requires
      demonstration of a series of attributes including patient-centred care. AIM: The
      national GP Patient Survey (GPPS) was used to determine the characteristics of
      general practices scoring highly in responses relating to the professional skills
      and characteristics of doctors. Specifically, to determine whether active
      participation in postgraduate GP training was associated with more positive
      experiences of care. DESIGN AND SETTING: Retrospective cross-sectional study in
      general practices in England. METHOD: Data were obtained from the national QOF
      dataset for England, 2011/12 (8164 general practices); the GPPS in 2012 (2.7
      million questionnaires in England; response rate 36%); general practice and
      demographic characteristics. Sensitivity analyses included local data validated
      by practice inspections. OUTCOME MEASURES: multilevel regression models adjusted
      for clustering. RESULTS: GP training practice status (29% of practices) was a
      significant predictor of positive GPPS responses to all questions in the 'doctor
      care' (n = 6) and 'overall satisfaction' (n = 2) domains but not to any of the
      'nurse care' or 'out-of-hours' domain questions. The findings were supported by
      the sensitivity analyses. Other positive determinants were: smaller practice and
      individual GP list sizes, more older patients, lower social deprivation and fewer
      ethnic minority patients. CONCLUSION: Based on GPPS responses, doctors in GP
      training practices appeared to offer more patient-centred care with patients
      reporting more positively on attributes of doctors such as 'listening' or 'care
      and concern'.

PMID- 24567657
TI  - Making sense of patients' internet forums: a systematic method using discourse
      analysis.

PMID- 24567658
TI  - Tenure in current captive setting and age predict personality changes in adult
      pigtailed macaques.
AB  - Personality change in nonhuman primates is a topic that warrants more research
      attention. Many studies focus on intraindividual repeatability, but few note
      population-wide trends in personality change. In part, this results from the
      large sample size that is required to detect such trends. In the present study,
      we measured personality in a large sample (N = 293) of adult, mother-reared
      pigtailed macaques, Macaca nemestrinam, over a period of 3 years. We looked at
      four personality components (sociability towards humans, cautiousness,
      aggressiveness and fearfulness) derived from behavioural observations at two to
      four time points per subject. We found these components to have repeatabilities
      similar to those reported elsewhere in the literature. We then analysed
      population-wide changes in personality components over time using a linear mixed
      effects model with three predictors: entry age at the current primate facility,
      tenure at the primate facility at the time of the first personality test and time
      elapsed since the first personality test. We found that adult personality changed
      with life experiences (here, tenure at the facility where tested) and age.
      Throughout adulthood, pigtailed macaques became less cautious and more
      aggressive. At the same time, subjects became less cautious and more sociable
      with increasing time in individual caging at the current primate research
      facility. We also found that individuals differed significantly in their
      personality consistency. Other researchers may benefit by applying similar
      methodology to that described here as they extrapolate about personality measures
      over time.

PMID- 24567659
TI  - The Effects of Student and Text Characteristics on the Oral Reading Fluency of
      Middle-Grade Students.
AB  - We evaluated the effects of student characteristics (sight word reading
      efficiency, phonological decoding, verbal knowledge, level of reading ability,
      grade, gender) and text features (passage difficulty, length, genre, and language
      and discourse attributes) on the oral reading fluency of a sample of middle
      school students in Grades 6-8 (N = 1,794). Students who were struggling (n = 704)
      and typically developing readers (n = 1,028) were randomly assigned to read five
      1-min passages from each of 5 Lexile bands (within student range of 550 Lexiles).
      A series of multilevel analyses showed that student and text characteristics
      contributed uniquely to oral reading fluency rates. Student characteristics
      involving sight word reading efficiency and level of decoding ability accounted
      for more variability than reader type and verbal knowledge, with small, but
      statistically significant effects of grade and gender. The most significant text
      feature was passage difficulty level. Interactions involving student text
      characteristics, especially attributes involving overall ability level and
      difficulty of the text, were also apparent. These results support views of the
      development of oral reading fluency that involve interactions of student and text
      characteristics and highlight the importance of scaling for passage difficulty
      level in assessing individual differences in oral reading fluency.

PMID- 24567660
TI  - Does caring for your spouse harm one's health? Evidence from a United States
      nationally-representative sample of older adults.
AB  - The purpose of this article is to investigate the relationship between spousal
      care-giving and declines in functioning and self-rated health among older care
      givers. The authors used data from the 2000 and 2002 waves of the United States
      Health and Retirement Study, a biennial longitudinal survey of a nationally
      representative cohort of adults aged 50 or more years. Two outcomes were
      examined, declines in functioning and declines in self-rated health. Care-givers
      were classified into three groups: no care-giving, less than 14 hours of care
      giving per week, and 14 or more hours care-giving per week. To assess declines in
      functioning, two summary scores were created of limitations in basic and
      instrumental Activities of Daily Living. To assess declines in self-rated health,
      we compared responses from 2000 and 2002. In the fully adjusted models, care
      giving hours did not have an independent effect on declines in functioning or
      self-rated health. The relationship between care-giving hours and declines in
      functioning and self-rated health is probably attributable to socio-demographic
      characteristics, mainly age. The findings suggest that spousal care-giving does
      not of itself harm functional health or perceived health among older adult care
      givers. Understanding the differential effects of these socio-economic
      characteristics with care-giving hours on health will be useful in promoting the
      health of older adult care-givers and treating their disorders.

PMID- 24567661
TI  - Sample size determination for paired right-censored data based on the difference
      of Kaplan-Meier estimates.
AB  - Sample size determination is essential to planning clinical trials. Jung (2008)
      established a sample size calculation formula for paired right-censored data
      based on the logrank test, which has been well-studied for comparing independent
      survival outcomes. An alternative to rank-based methods for independent right
      censored data, advocated by Pepe and Fleming (1989), tests for differences
      between integrated weighted Kaplan-Meier estimates and is more sensitive to the
      magnitude of difference in survival times between groups. In this paper, we
      employ the concept of the Pepe-Fleming method to determine an adequate sample
      size by calculating differences between Kaplan-Meier estimators considering pair
      wise correlation. We specify a positive stable frailty model for the joint
      distribution of paired survival times. We evaluate the performance of the
      proposed method by simulation studies and investigate the impacts of the accrual
      times, follow-up times, loss to follow-up rate, and sensitivity of power under
      misspecification of the model. The results show that ignoring the pair-wise
      correlation results in overestimating the required sample size. Furthermore, the
      proposed method is applied to two real-world studies, and the R code for sample
      size calculation is made available to users.

PMID- 24567662
TI  - Synthesis, Characterization, and Catalytic Activity of Ni(II) Alkyl Complexes
      Supported by Pyrrole-Diphosphine Ligands.
AB  - The organometallic Ni(II) chemistry of the pyrrole-based pincer ligands, (P2RPyr)
      (P2RPyr = 2,5-(R2PCH2)2C4H2N, R = Ph or Cy) is reported. Reactions of Grignard
      reagents with [NiCl(P2R Pyr)] afford a variety of alkyl and aryl complexes
      (methyl, ethyl, benzyl, phenyl, and allyl) that all display square planar
      geometries about nickel. The hydride complex, [NiH(P2CyPyr)], can also prepared
      either through treatment of [NiCl(P2CyPyr)] with LiHBEt3, or by reaction of
      H(P2RPyr) with [Ni(COD)2] (COD = 1,4-cyclooctadiene). Reactions of the methyl and
      hydride complexes with CO and CO2, respectively, evince clean migratory insertion
      chemistry of the Ni-C and Ni-H bonds. Both the alkyl and chloride complexes are
      active catalysts for the Kumada coupling of aryl chlorides and aryl or alkyl
      Grignard reagents at room temperature. The solid-state structures of several of
      the complexes are reported.

PMID- 24567663
TI  - Microfabrication of High-Resolution Porous Membranes for Cell Culture.
AB  - Microporous membranes are widely utilized in cell biology to study cell-cell
      signaling and cell migration. However, the thickness and low porosity of
      commercial track-etched membranes limit the quality of cell imaging and the
      degree of cell-cell contact that can be achieved on such devices. We employ
      photolithography-based microfabrication to achieve porous membranes with pore
      diameter as small as 0.9 MUm, up to 40% porosity, and less than 5% variation in
      pore size. Through the use of a soap release layer, membranes as thin as 1 MUm
      can be achieved. The thin membranes minimally disrupt contrast enhancement
      optics, thus allowing good quality imaging of unlabeled cells under white light,
      unlike commercial membranes. In addition, the polymer membrane materials display
      low autofluorescence even after patterning, facilitating high quality
      fluorescence microscopy. Finally, confocal imaging suggests that substantial cell
      cell contact is possible through the pores of these thin membranes. This membrane
      technology can enhance existing uses of porous membranes in cell biology as well
      as enable new types of experiments.

PMID- 24567664
TI  - Effect of Dual-task Rehabilitative Training on Cognitive and Motor Function of
      Stroke Patients.
AB  - [Purpose] To determine the effect of dual-task training with cognitive tasks on
      cognitive and walking ability after stroke. [Subjects and Methods] Twenty
      patients diagnosed with stroke participated in this study. All participants were
      receiving a traditional rehabilitation program 5 days a week. Dual-task and
      single-task training were additionally performed for 4 weeks, 3 days a week. The
      Stroop test, Timed Up and Go (TUG) test, 10-Meter Walk Test (10MWT), and Figure
      of-8 Walk Test (F8WT) were used to measure cognitive and walking abilities and
      were evaluated 3 times (before and after training and at the 2-week follow-up).
      [Results] Dual-task training improved cognitive and walking abilities, and dual
      task training subjects' performance was better than single-task training
      subjects' performance. In addition, these training benefits were maintained for 2
      weeks. [Conclusion] Dual-task training improves cognitive and walking abilities
      of patients with stroke. 

PMID- 24567665
TI  - Effects of extracorporeal shockwave therapy on patients with chronic low back
      pain and their dynamic balance ability.
AB  - [Purpose] The purpose of the present study was to examine the effects of
      extracorporeal shockwave therapy (ESWT) for patients with chronic low back pain
      and their dynamic balance ability. [Subjects] Twenty-eight patients with chronic
      low back were divided into an extracorporeal shockwave therapy group (ESWTG:
      n=13) and a conservative physical therapy group (CPTG, n=15). [Methods] An
      exercise program that included Williams' exercises and McKenzie's exercises was
      performed by both groups. The program was implemented twice a week for six weeks.
      The visual analog scale (VAS) was used to measure the chronic low back pain of
      the patients. Their dynamic balance ability was measured with BioRescue.
      [Results] The within-group comparison of the VAS of the ESWTG and the CPTG showed
      significant improvements after the intervention. In the VAS comparison between
      the groups after the treatment, the ESWTG showed a significantly larger
      improvement. In the within-group comparison of dynamic balance ability, the ESWTG
      showed significant improvements after the intervention in SAPLS, SAPRS, SAPFS,
      SAPBS, and TSA, and the CPTG showed significant improvements in SAPLS and SAPBS.
      In the between-group comparison of the dynamic balance ability after the
      treatment, the ESWTG showed significantly larger improvements in their SAPLS,
      SAPRS, SAPFS, and TSA. [Conclusion] The exercise program combined with the ESWT
      relieved chronic back pain more than the exercise program combined with the CPT.
      The former was also more effective at improving the patients' dynamic balance
      ability in terms of SAPLS, SAPRS, SAPFS, and TSA. 

PMID- 24567666
TI  - Effect of skin resection on the improvement of joint contractures in rats.
AB  - The effect of skin resection on joint contracture was determined by comparing the
      first measurement of range of motion after cast removal and the second
      measurement after the skin resection. This study aimed to verify that both the
      joint movement during the measurement and skin affect range of motion. [Subjects]
      Twelve female Wistar rats were used. [Methods] The right hind limb ankle of each
      rat was immobilized in complete plantar flexion in a cast. In the resection group
      (n = 6), the skin of the right hind limb ankle was removed surgically, but not in
      the non-resection group (n = 6). In the resection group, the first measurement of
      the dorsiflexion angle was obtained after the cast was removed, and the second
      measurement was obtained after skin resection. In the non-resection group, both
      measurements of the dorsiflexion angle were obtained soon after the cast was
      removed. [Results] Compared with the non-resection group, the resection group
      showed a significant increase between the first and second measurements of range
      of motion. [Conclusion] These results show that range of motion is substantially
      affected by skin, in addition to joint movement, during measurement. 

PMID- 24567667
TI  - An Investigation into Reliability of Knee Extension Muscle Strength Measurements,
      and into the Relationship between Muscle Strength and Means of Independent
      Mobility in the Ward: Examinations of Patients Who Underwent Femoral Neck
      Fracture Surgery.
AB  - [Purpose] The purpose of the present study was to investigate the reliability of
      isometric knee extension muscle strength measurement of patients who underwent
      femoral neck fracture surgery, as well as the relationship between independent
      mobility in the ward and knee muscle strength. [Subjects] The subjects were 75
      patients who underwent femoral neck fracture surgery. [Methods] We used a hand
      held dynamometer and a belt to measure isometric knee extension muscle strength
      three times, and used intraclass correlation coefficients (ICCs) to investigate
      the reliability of the measurements. We used a receiver operating characteristic
      curve to investigate the cutoff values for independent walking with walking
      sticks and non-independent mobility. [Results] ICCs (1, 1) were 0.9 or higher.
      The cutoff value for independent walking with walking sticks was 0.289 kgf/kg on
      the non-fractured side, 0.193 kgf/kg on the fractured side, and the average of
      both limbs was 0.238 kgf/kg. [Conclusion] We consider that the test-retest
      reliability of isometric knee extension muscle strength measurement of patients
      who have undergone femoral neck fracture surgery is high. We also consider that
      isometric knee extension muscle strength is useful for investigating means of
      independent mobility in the ward. 

PMID- 24567668
TI  - Relationship between the Degree of Thoracic Deformity and the Angle Formed by a
      Line Connecting the Sternum and the Spinous Process of the Vertebrae in
      Individuals with Severe Motor and Intellectual Disorders.
AB  - [Purpose] The purpose of this study was to examine the relationship between the
      degree of thoracic deformity (TD) and the angle formed by a line drawn on
      transverse plane computed tomography (CT) images, connecting the sternum and the
      spinous process of the vertebrae at the level of the xiphisternum, and the
      perpendicular line from the floor (ANGLE), in individuals with severe motor and
      intellectual disorders (SMID). [Subjects] Twenty seven individuals with SMID were
      examined. [Methods] CT transverse images were acquired at the level of the
      xiphisternum of each patient. Two protocols were used to measure the
      anteroposterior (AP) and laterolateral (LL) diameters. The largest AP diameters
      were measured along a perpendicular line from the floor (protocol 1) and the line
      from the midline of the sternum to the spinous process of the vertebrae (protocol
      2). The largest LL diameters were measured along the lines perpendicular to the
      AP diameters in each protocol. The ratios of the AP to LL diameters and the
      difference between the ratios of protocols 1 and 2 (DIFFERENCE) were calculated.
      [Results] Moderate to good correlation between DIFFERENCE and ANGLE was observed,
      and DIFFERENCE became larger with increasing ANGLE. [Conclusions] These results
      show that ANGLE indicates the degree of TD. 

PMID- 24567669
TI  - The effects of hippotherapy on elderly persons' static balance and gait.
AB  - [Purpose] The aim of this study was to examine the effects of hippotherapy on
      elderly persons' static balance and gait. [Subjects and Methods] Twenty-two
      elderly persons residing in the community were randomly divided into a
      hippotherapy group and a treadmill group and they conducted exercise for eight
      weeks. [Results] Step lengths increased significantly, and step time and sway
      path lengths significantly decreased in both groups. A comparison of sway path
      lengths after the intervention between the two groups revealed that the
      hippotherapy group showed larger decreases than the treadmill group. [Conclusion]
      The results of this study indicate that hippotherapy may improve the static
      balance and gait of elderly persons residing in the community. 

PMID- 24567670
TI  - Effect of horseback riding simulation machine training on trunk balance and gait
      of chronic stroke patients.
AB  - [Purpose] The purpose of this study was to assess the effect of horseback riding
      simulation machine training on trunk balance and gait of patients with chronic
      stroke. [Subjects and Methods] The subjects were 20 patients hospitalized for
      treatment after being diagnosed with stroke. Horseback riding simulation training
      was provided for 30 minutes, 5 times a week, for 6 weeks. Trunk balance was
      assessed using the Trunk Impairment Scale (TIS) and a balance measuring device
      (Biorescue, RM ingenierie, France), and gait ability was measured using the
      Functional Gait Assessment (FGA) and a gait analyzer (GAITRite, CIR system Inc.,
      USA). [Results] There were significant changes in movement area, distance and
      velocity of body sway as measured by the TIS and the balance measuring device,
      and in gait velocity, cadence, stride length and double limb support as measured
      by the FGA and gait analyzer. [Conclusion] Horseback riding simulation training
      improved the trunk balance and gait of chronic stroke patients. This present
      study provides preliminary objective data for future research, and useful
      clinical information for physical therapists using horseback riding simulation
      machines as a treatment modality for patients with chronic stroke. 

PMID- 24567671
TI  - How long can joint position sense be retained in memory by young healthy
      subjects?
AB  - [Purpose] The aim of the present study was to investigate how long joint position
      sense (JPS) can be retained in memory. [Subjects] Eleven healthy subjects (5 men
      and 6 women) were enrolled in this study. [Methods] Subjects memorized a specific
      joint position visually, and then they were asked to reproduce without visual aid
      the position at 3 different time intervals: immediately, 5 minutes post
      memorization, and 30 minutes post-memorization. [Results] Differences in JPS
      between time intervals of immediate and 30 minutes post-memorization were
      statistically significant with the exception of knee flexion at 60 degrees  with
      a 5 kg load. Differences in reproduced JPS between time intervals of immediately
      and 5 minutes post-memorization were not statistically significant. [Conclusions]
      The results suggest that JPS can be retained in memory for approximately 5
      minutes. 

PMID- 24567672
TI  - A study on dispersion and rate of fat infiltration in the lumbar spine of
      patients with herniated nucleus polpusus.
AB  - [Purpose] This study investigated the relationship between herniated nucleus
      pulposus (HNP) and fat infiltration of muscles around the spine by measuring body
      mass index (BMI) and fat infiltration of the muscles around the spine. [Subjects
      and Methods] Subjects were 82 people, both men and women they were divided into
      two groups, a normal group and a patient group who were suffering from serious
      HNP between L4 and L5. Of the anthropometric measurement, and fat infiltration
      muscles by measuring the cross-sectional area from the center of the disc to the
      muscle around the spine and the cross-sectional area of fat infiltration.
      [Results] Fat infiltration rate of each lumbar layer in the normal group was
      different L34-L45 and L45-L5S1, but not between L23-L34. Fat infiltration in the
      muscle between the normal group and patients with HNP was different in the layers
      and the difference was greatest in the L5-S1 layer. [Conclusion] We performed
      correlation analysis of BMI and the total fat infiltration rate in each group to
      find the relationship between obesity and fat infiltration in the lumbar spine.
      Fat infiltration increased, and normal people or patients with chronic back pain
      are considered to be exposed to other diseases as fat infiltration in the lumbar
      spine increases. 

PMID- 24567673
TI  - The usefulness of performance matrix tests in locomotor system evaluation of
      girls attending a ballet school - preliminary observation.
AB  - [Purpose] Learning ballet is connected with continuous use of the locomotor
      system while subjecting it to high loads. Therefore, we conducted some research
      defining the appearance of weak links in the motor system, in order to eliminate
      the risk of injury. [Methods] Fifty-two female students of a ballet school were
      examined. To identify weak links, low-threshold Performance Matrix tests were
      performed. An analysis of weak link occurrence in the locomotor system was
      carried out, using two way analysis of variance ANOVA Tukey's HSD test,
      clustering methods and Principal Component Analysis (PCA). [Results] The average
      age of the subjects was 11.64+/-0.53 years (mean +/- standard deviation), their
      average body height was 151.1+/-7.5 cm, their average body weight was 35.92+/
      5.41 kg, and their average time of learning at ballet school was 2.17+/-0.65
      years. We found that there were significant differences in weak links occurrence
      in the motor system of every girl examined. [Conclusions] Weak links were found
      in every location of the motor system. Our results show that the influence of
      weak link location is essentially different from their occurrence, and that
      learning ballet has a significantly different impact on the number of weak links
      in different locations. 

PMID- 24567674
TI  - Short-term Effects of a Proprioceptive Training Session with Unstable Platforms
      on the Monopodal Stabilometry of Athletes.
AB  - To analyze the short-term effects of a proprioceptive session on the monopodal
      stabilometry of athletes. [Subjects] Thirty-seven athletes were divided into a
      control group (n=17) and an experimental group (n=20). [Methods] Both groups
      performed a conventional warm-up, after which a 25-minute proprioceptive session
      on ustable platforms was carried out only by the experimental group. Before the
      training session, all athletes carried out a single-leg stabilometry test which
      was repeated just after training, 30 minutes, 1 hour, 6 hours and 24 hours later.
      [Results] Analysis of covariance (alpha=0.05) revealed that the experimental
      group had lower values than the control group in length and velocity of center of
      pressure (CoP) of left-monopodal stance and in velocity of CoP of right-monopodal
      stance in post-training measurements. Also, the experimental group had values
      closer to zero for the CoP position in the mediolateral and anteroposterior
      directions of left-monopodal stance (Xmeanl and Ymeanl) and the anteroposterior
      direction in on right-monopodal stance (Ymeanr) in post-training measurements.
      Within-group analysis of Xmeanl and Ymeanl, length and velocity of CoP in right
      monopodal stance showed continuous fluctuations of values between sequential
      measurements in the control group. [Conclusion] Proprioceptive training on
      unstable platfoms after a warm-up stabilizes the position of CoP in the
      anteroposterior and mediolateral directions and decreases CoP movements in short
      term monopodal stability of athletes. 

PMID- 24567675
TI  - Effect of an Intermittent Eight-hour Joint Fixation Period on Joint Contractures
      in Rats.
AB  - [Purpose] It has been shown that an eight-hour joint fixation daily (i.e. for the
      remaining 16 hours, rats were set free in the cage without joint fixation) for
      one week induces a joint contracture. The purpose of this study was to
      investigate the difference between an 8 hours continuous joint fixation and an 8
      hours intermittent joint fixation per day (two 4 hours joint fixations) in the
      development of joint contractures in rats. [Subjects and Methods] The subjects of
      this study were 34 Wistar rats. On the first day, all of the rats' right ankle
      dorsiflexion angles were measured. The right hind limbs of all the rats were
      fixed in plantar flexion, and then the rats were divided into three groups as
      follows: Group 1 was in continuous fixation for 24 hours a day; Group 2 was in
      continuous fixation for 8 hours a day; Group 3 was in intermittent fixation for 8
      hours a day. The fixation was performed daily for seven consecutive days. On the
      last day, ankle dorsiflexion angles of all the rats were measured after the casts
      had been removed. [Results] The development of joint contractures was
      statistically significant for Groups 1 and 2. [Conclusion] Our results indicate
      that 8 hours a day of continuous fixation induces a joint contracture, but 8
      hours a day of intermittent fixation does not. 

PMID- 24567676
TI  - Lumbar Extension during Stoop Lifting is Delayed by the Load and Hamstring
      Tightness.
AB  - [Purpose] This study investigated the relationship between lumbar pelvic rhythm
      and the physical characteristics of stoop lifting. [Subjects and Methods]
      Participants performed a stoop lifting task under two conditions: with and
      without load. We assessed the lumbar kyphosis and sacral inclination angles using
      the SpinalMouse((r)) system, as well as hamstring flexibility. During stoop
      lifting, surface electromyograms and the lumbar and sacral motions were recorded
      using a multi-channel telemetry system and flexible electrogoniometers. [Results]
      In the initial phase of lifting, lumbar extension was delayed by load; the delay
      showed a negative correlation with sacral inclination angle at trunk flexion,
      whereas a positive correlation was observed with electromyogram activity of the
      lumbar multifidus. Additionally, a positive correlation was observed between
      sacral inclination angle and hip flexion range of motion during the straight leg
      raise test. [Conclusion] We found that a disorder of the lumbar pelvic rhythm can
      be caused by both load and hamstring tightness. In the initial phase of stoop
      lifting, delayed lumbar extension is likely to lead to an increase in spinal
      instability and stress on the posterior ligamentous system. This mechanism shows
      that stoop lifting of a load may be harmful to the lower back of people with
      hamstring tightness. 

PMID- 24567677
TI  - Relationship between Lower Limb Muscle Structure and Function in Cerebral Palsy.
AB  - [Purpose] The purpose of the study was to provide information for intervention by
      comparing lower limb muscle thickness, gross motor function and functional level
      of activity daily living between cerebral palsy (CP) and mental retardation (MR).
      [Subjects] Sixty subjects participated: 38 CP and 9 MR subjects and 13 normally
      developing infants. [Methods] Ultrasonography and a manual muscle tester were
      used for measuring the thickness and strength of knee extensor and ankle plantar
      flexor muscles. The Gross Motor Function Measure (GMFM) and Wee Functional
      Independence Measure (WeeFIM) were used to evaluate level of gross motor and
      independence level. [Results] Knee extensor thicknesses of CP and MR subjects
      were thinner than those of normally developing infants. Strengths of knee
      extensor and ankle plantar flexor showed differences being strongest in normally
      developing infants, followed by MR, and CP. Subjects in the examination of GMFM,
      there were no significant differences between CP and MR. A decline in social
      cognition of MR subjects was found in the examination of WeeFIM. [Conclusion] CP
      and MR subjects had smaller muscle thicknesses and strengths than those of
      normally developing infants, and lower gross motor function and functional
      independent level. 

PMID- 24567678
TI  - Analysis of the factors influencing functional outcomes in patients with spinal
      cord injury.
AB  - [Purpose] The extent of functional independence ultimately achieved by an
      individual patient will be influenced by a variety of medical and non-medical
      factors. [Subjects and Methods] this study included 419 patients with spinal cord
      lesions treated in the Clinic for Rehabilitation "Dr M. Zotovic", Belgrade,
      Serbia, from January 2000 to December 2009. The patients were divided in two
      groups according to achievement of increase in Functional Independence Measure
      (FIM) score of more than 13 at discharge compared to admission. A variety of
      clinical variables were followed in both groups. [Results] one hundred twenty-one
      patients (28.9%) showed improvements in FIM score of <=13, while 298 (71.1%)
      patients showed an increases in FIM score of >13 at discharge compared to
      admission. Better functional recovery was observed in patients with non-traumatic
      spinal cord lesions, lower neurological levels of the lesion (OR = 6.07), and in
      patients treated surgically, but the level of the spinal cord lesion was the most
      influential factor affecting outcome. [Conclusion] the patients with spinal cord
      lesions should not only be grouped by traumatic and non-traumatic lesions only,
      but also sub-categorized, according to the etiology, level of injury and
      treatment method. 

PMID- 24567679
TI  - Effects of Abdominal Stimulation during Inspiratory Muscle Training on
      Respiratory Function of Chronic Stroke Patients.
AB  - [Purpose] The purpose of the present study was to verify a new method for
      improving respiratory functions by applying both abdominal stimulation and
      inspiratory muscle training (IMT) to train the inspiratory muscle and the
      expiratory muscle simultaneously, to improve the efficiency of IMT of chronic
      stroke patients. [Subjects] Eighteen stroke patients were randomly assigned to an
      experimental group (n = 9) and a control group (n = 9). [Methods] The
      experimental group was administered IMT with abdominal stimulation, and the
      control group was administered only IMT. During the intervention period, the
      experimental group and control group received training 20 min/day, 3 times/wk,
      for 4 weeks. To examine the lung functions of the subjects, FVC, FEV1, PEF, and
      FEF25-75 were measured using an electronic spirometer. The diaphragm thickness
      ratio was calculated from measurements made with a 7.5-MHz linear probe
      ultrasonic imaging system. [Result] The experimental group and the control group
      showed significant increases in diaphragm thickness ratio on the paretic side,
      but not on the non-paretic side. With regard to lung function, the experimental
      group showed significant increases in FEV1, PEF, and FEF25-75. The changes
      between before and after the intervention in the two groups were compared with
      each other, and the results showed significant differences in FEV1 and PEF.
      [Conclusion] The present study identified that IMT accompanied by abdominal
      stimulation improved the pulmonary function of chronic stroke patients. 

PMID- 24567680
TI  - An Analysis of Muscle Activities of Healthy Women during Pilates Exercises in a
      Prone Position.
AB  - [Purpose] This study analyzed the activities of the back and hip muscles during
      Pilates exercises conducted in a prone position. [Subjects] The subjects were 18
      healthy women volunteers who had practiced at a Pilates center for more than
      three months. [Methods] The subjects performed three Pilates exercises. To
      examine muscle activity during the exercises, 8-channel surface electromyography
      (Noraxon USA, Inc., Scottsdale, AZ) was used. The surface electrodes were
      attached to the bilateral latissimus dorsi muscle, multifidus muscle, gluteus
      maximus, and semitendinous muscle. Three Pilates back exercises were compared:
      (1) double leg kick (DLK), (2) swimming (SW), and (3) leg beat (LB). Electrical
      muscle activation was normalized to maximal voluntary isometric contraction.
      Repeated measures analysis of variance was performed to assess the differences in
      activation levels among the exercises. [Results] The activity of the multifidus
      muscle was significantly high for the SW (52.3+/-11.0, 50.9+/-9.8) and LB
      exercises(51.8+/-12.8, 48.3+/-13.9) and the activity of the semitendinosus muscle
      was higher for the LB exercise (49.2+/-8.7, 52.9+/-9.3) than for the DLK and SW
      exercises. [Conclusion] These results may provide basic material for when Pilates
      exercises are performed in a prone position and may be useful information on
      clinical Pilates for rehabilitation programs. 

PMID- 24567681
TI  - Concurrent Validity and Test-retest Reliability of the OPTOGait Photoelectric
      Cell System for the Assessment of Spatio-temporal Parameters of the Gait of Young
      Adults.
AB  - [Purpose] The purpose of this study was to investigate the concurrent validity
      and test-retest reliability of the recently introduced OPTOGait Photoelectric
      Cell System for the assessment of spatio-temporal parameters of gait. [Subjects]
      Twenty healthy young adults (mean age = 27.35, SD = 7.4) were asked to walk 3
      times on walkway at a comfortable speed. [Methods] Concurrent validity was
      assessed by comparing data obtained using the OPTOGait and GAITRite systems, and
      reliability was assessed by comparing data from the first and third OPTOGait
      sessions. [Results] Concurrent validity, as identified by intra-class correlation
      coefficients (ICC (2, 1) = 0.929-0.998), coefficients of variation (CVME = 0.32
      11.30%), and 95% limits of agreement, showed high levels of correlation. In
      addition, the test-retest reliability of the OPTOGait Photoelectric Cell System
      was demonstrated as showing a high level of correlation with all spatio-temporal
      parameters by intra-class correlation coefficients (ICC (3, 1) = 0.785-0.952),
      coefficients of variation (CVME = 1.66-4.06%), 95% limits of agreement, standard
      error of measurement (SEM = 2.17-5.96%), and minimum detectable change (MDC95% =
      6.01-16.52%). [Conclusion] The OPTOGait Photoelectric Cell System has strong
      concurrent validity along with relative and absolute test-retest reliabilities.
      This portable system with easy-to-use features can be used for clinical
      assessments or research purposes as an objective means of assessing gait. 

PMID- 24567682
TI  - Thoracic coupled motions of korean men in good health in their 20s.
AB  - [Purpose] The purpose of this study was to investigate thoracic coupled motions
      of 20 Korean young individuals. [Methods] Thoracic motion of twenty healthy male
      college students aged 23.2+/-3.1 was examined. The coupled motions of the
      thoracic regions T1-4, T4-8, T8-12 were measured using a three dimensional motion
      capture system. [Results] Coupled axial rotation in the same direction as lateral
      bending was observed in T1-T4 and T4-T8 in the neutral, flexed, and extended
      postures of the thoracic spine. In T8-T12, coupled axial rotation in the same
      direction as lateral bending were observed in the neutral and flexed postures,
      while coupled axial rotation in the opposite direction was observed in an
      extended posture. [Conclusion] The patterns of coupled motions in the thoracic
      spine demonstrated some variability between postures and regions in vivo.
      However, coupled motions in the same direction were predominantly lateral flexion
      or axial rotation in the three postures. 

PMID- 24567683
TI  - The effects of combination patterns of proprioceptive neuromuscular facilitation
      and ball exercise on pain and muscle activity of chronic low back pain patients.
AB  - [Purpose] The purpose of this study was to compare two methods for the muscle
      stabilization of the trunk of patients with chronic low back pain. The methods
      comprised combination patterns of proprioceptive neuromuscular facilitation (PNF)
      and ball exercise. [Subjects and Methods] The subjects were 40 volunteers who had
      low back pain. All subjects were randomly assigned to either a group which
      received proprioceptive neuromuscular facilitation or a group which performed
      ball exercise. Measurements were taken four times in total, at pre-intervention,
      two weeks later, four weeks later, and six weeks later. The main measurement
      methods used were the visual analogue scale (VAS) for pain and electromyography
      (EMG) for muscle activity. [Results] VAS and EMG activity were significantly
      reduced in the PNF combination pattern group and the ball exercise group. A
      comparison of the groups showed significant differences. In VAS and EMG activity;
      in particular, the combination pattern group using PNF increased EMG activity
      more than the ball exercise group did after six weeks of intervention.
      [Conclusion] This study showed that PNF combination pattern training for six
      weeks was more effective for patients with low back pain than performing ball
      exercise. 

PMID- 24567684
TI  - Comparative analysis of acromiohumeral distances according to the locations of
      the arms and humeral rotation.
AB  - [Purpose] The purpose of this study was to compare the potential effects of
      resistance exercise according to the positions of the arms and the rotation of
      the humerus on the subhumeral acromial space. [Subjects] The study subjects were
      34 subjects without shoulder pain. [Methods] Ultrasonographic measurements of the
      acromiohumeral distance of the subjects were made at three shoulder positions: 90
      degrees  flexion, scaption at 90 degrees  abduction, and 90 degrees  abduction in
      an upright sitting position. The subjects were instructed to vertically push
      against a table to the maximum level with the humerus in internal, neutral, and
      external rotation. The measurements were made three times in each position.
      [Results] There was a significant difference in acromiohuneral distance between
      neutral and internal rotation of the humerus, and between external rotation and
      internal rotation of the humerus. In the scaption position, there was a
      significant difference between neutral and internal rotation of the humerus, and
      between external rotation and internal rotation of the humerus. In the 90 degrees
      flexion position, there was a significant difference between neutral and
      internal rotation, and between neutral and external rotation. There was a
      significant difference between the flexion position and the abduction position,
      and between the flexion position and the scaption position. In terms of the
      internal rotation of the humerus, there was a significant difference between 90
      degrees  flexion and 90 degrees  abduction. [Conclusion] These findings can be
      applied in exercises prescribed to increase the acromiohumeral distance and to
      aid the treatment and evaluation of shoulder dysfunctions. 

PMID- 24567686
TI  - Effects of a Walking Program on Self-management and Risk Factors of Metabolic
      Syndrome in Older Korean Adults.
AB  - [Purpose] The aim of this study was to determine the effects of a 12-week walking
      program on increasing an individual's self-management and decreasing the risk
      factors of metabolic syndrome in the older adult population. [Subjects] A total
      of 31 older adults participated in this study. Eighteen participants in the
      experimental group and 13 controls completed the pretest and posttest measures. A
      walking exercise and health education were provided for the experimental group.
      Data were analyzed by ANCOVAs to examine group differences. [Results] At the end
      of the 12-week study period, the experimental group showed a significant
      improvement in individuals' ability to self-manage their health compared to the
      control group. Also, there were significant differences between the two groups in
      the total numbers of risk factors of metabolic syndrome, systolic blood pressure
      and BMI. No significant difference in blood sugar levels, HDL-C, waist
      circumference, and triglyceride levels were found between the experimental and
      control group. [Conclusion] This study revealed that a combination of health
      education and for walking exercise can lead to improved lifestyle management and
      reduce risk factors of metabolic syndrome for the elderly population of Korea. 

PMID- 24567685
TI  - Spinal reflex arc excitability corresponding to the vastus medialis obliquus and
      vastus medialis longus muscles.
AB  - [Purpose] The gross morphology of the vastus medialis (VM) muscle has been
      thoroughly described. However, there is insufficient evidence of physiological
      differentiation between the VM obliquus (VMO) and VM longus (VML). To elucidate
      spinal reflex arc excitability in two divisions of the VM, we compared H-reflexes
      and T-waves in VMO and VML. [Subjects] Twenty-three healthy male volunteers
      participated in this study. [Methods] The H-reflex was evoked from the VMO and
      VML by electrical stimulation of the femoral nerve during knee extension at 10%
      maximal voluntary isometric contraction. Also, the patellar tendon was tapped by
      an examiner using an electrical tendon hammer, and a component of the compound
      muscle action potential (T-wave) was recorded. [Results] The configurations of
      the H-reflex and T-wave were sharp and slow in VMO and VML, respectively. No
      significant differences in the amplitudes of the H-reflexes and T-waves were
      observed between VMO and VML. The durations of VML H-reflexes and T-waves were
      significantly longer than those in VMO. [Conclusion] Spinal reflex arc
      excitability corresponding to VMO and VML was similar. However, the
      configurations and durations of the H-reflex and T-wave were differentiated with
      electromyography. On the basis of these findings, we suggest that VMO and VML are
      electrophysiologically distinct entities. 

PMID- 24567687
TI  - Exercise training improves cardiac autonomic nervous system activity in type 1
      diabetic children.
AB  - [Purpose] We investigated the effect exercise training has on cardiac autonomic
      nervous system (ANS) and cardiovascular risk profiles in children with type 1
      diabetes mellitus (DM). [Subjects] Fifteen type 1 DM children (all boys; 13.0+/
      1.0 years of age) were enrolled in the study. [Methods] The subjects received
      exercise training three times a week in a 12-week program. Each child was asked
      to walk on a treadmill to achieve an exercise intensity of VO2max 60%. ANS
      activity was measured by power spectral analysis of the electrocardiogram (ECG).
      Blood samples were obtained for serum lipid profiles. To evaluate Doppler-shifted
      Fourier pulsatility index (PI) analysis, a 5-MHz continuous wave Doppler
      (VASCULAB D10) set was used to measure forward blood flow velocity (FLOW) in the
      radial artery. [Results] Total and low-frequency (LF) power of heart rate
      variability increased significantly after exercise intervention. Total
      cholesterol (TC) levels were significant lower after exercise intervention. Total
      and high-frequency (HF) power were significantly correlated with higher TC
      levels, but diastolic blood pressure and HF was significantly correlated with
      lower TC levels. [Conclusion] Regular exercise intervention should be prescribed
      for children with type 1 DM. 

PMID- 24567688
TI  - Immediate Effect of Short-foot Exercise on Dynamic Balance of Subjects with
      Excessively Pronated Feet.
AB  - [Purpose] The aim of this study was to determine the immediate effect of short
      foot exercise (SFE) on the dynamic balance of subjects with excessively pronated
      feet. [Subjects] This study included 18 subjects with excessively pronated feet
      (navicular drop >= 10 mm) selected using the navicular drop test. [Methods] The
      limit of stability (LOS) was measured to determine the changes in the dynamic
      balance from before and after SFE in the standing and sitting positions. [Result]
      After the SFE, LOS increased significantly in all areas, namely, the left, right,
      front, back, and overall. [Conclusion] SFE immediately improved the dynamic
      balance of subjects with excessively pronated feet. Subsequent studies will be
      conducted to examine the effects of SFE performed over the long term on postural
      stability. 

PMID- 24567689
TI  - Reliability of the good balance system((r)) for postural sway measurement in
      poststroke patients.
AB  - [Purpose] The purpose of this study was to examine test-retest reliability of the
      Good Balance system((r)) for measurement of postural sway in poststroke patients.
      [Subjects] Sixty chronic stroke patients (40 men and 20 women; age 63.08 years;
      stroke duration 16.45 months) participated in this study. [Methods] Postural sway
      was evaluated using a force platform system (Good Balance system, Metitur Oy,
      Jyvaskyla, Finland). Two examiners measured postural sway for all participants
      during two separate testing sessions. The second measurement was performed one
      week after the first measurement. Intraclass correlation coefficients [ICC(2,1)]
      were used for estimation of reliability. [Results] The ICC (95% CI) for intra
      examiner reliability was good to very good, ranging from 0.69 to 0.93 (0.53
      0.96), and the ICC for inter-examiner reliability was good to very good, ranging
      from 0.85 to 0.98 (0.77-0.99). [Conclusion] The results of the current study
      indicated that the intra- and inter-examiner reliability of the Good Balance
      system((r)) for measurement of postural sway was good to very good. Therefore, we
      suggest that measurement of postural sway using the Good Balance system((r))
      would be useful for clinical assessment in poststroke patients. 

PMID- 24567690
TI  - Evaluation of the Lactate Threshold during Downhill Running in Rats.
AB  - [Purpose] The purpose of the present study was to investigate if lactate
      thresholds in rats could be accurately determined during downhill running in
      rats. [Subjects] Twenty-four female Wistar rats were used in this study. Rats
      were randomly divided into two groups: the level running group and downhill
      running group. [Methods] Catheters were inserted into the right external jugular
      veins of the rats. Two days after the operation, the rats performed incremental
      exercise tests. The level running group ran on a treadmill at a 0 degrees 
      incline; the downhill running group ran on a treadmill at a -16 degrees  incline.
      The lactate threshold was determined using the 2-line combination that minimizes
      the total sum of squares for fitting all data. [Results] Maximal running speeds
      and running speeds at the lactate threshold for the downhill running group were
      significantly higher than those for the level running group. [Conclusion] In this
      study, it was possible to accurately determine the lactate threshold during
      downhill running. These findings suggest that when the treadmill speed is the
      same, downhill running can be done at lower metabolic intensity than level
      running. 

PMID- 24567691
TI  - Effects of manual lymph drainage of the neck on EEG in subjects with
      psychological stress.
AB  - [Purpose] The present study investigated the effect of manual lymph drainage
      (MLD) of the neck on electroencephalography (EEG) in subjects with psychological
      stress. [Methods] Twenty-six subjects were randomly allocated to receive one 15
      min session of either MLD or resting on a bed (control). [Results] Analysis of
      EEG in the MLD group showed a significant increase in relaxation, manifested as
      an increase in average absolute and relative delta and alpha activity.
      [Conclusion] It is suggested that MLD provides acute neural effects that increase
      relaxation in subjects with psychological stress. 

PMID- 24567692
TI  - Acute effects of 5 min of plantar flexor static stretching on balance and gait in
      the elderly.
AB  - [Purpose] The purpose of this study was to examine the acute effects of five
      minutes of plantar flexor static stretching (PSS) on the balance and gait of the
      elderly. [Subjects and Methods] Twenty-five subjects aged 65 years and above
      performed 5 min of PSS in the form of wedge board standing. The sway length of
      each subject's center of mass was measured to examine the subject's static
      balance. It was measured by one minute of quiet standing with the eyes closed.
      Functional reach tests (FRTs), timed up and go tests (TUGs), and 10-meter walk
      tests (10MWTs) were performed to examine dynamic balance and gait before and
      after PSS. [Results] The outcome showed significant increases in sway distances
      (6.55 +/- 5.03 cm) after stretching. However, in the FRTs, TUGs, and 10MWTs, the
      reach distance and time did not show any significant changes. [Conclusion] These
      results suggest that the elderly subjects temporarily experienced difficulties in
      maintaining balance immediately after the PSS but that their dynamic balance and
      gait were not adversely affected after a short period of time. Therefore, to
      prevent falls and perform exercises in a safe way, it is recommended to allow
      patients to rest after performing PSS. 

PMID- 24567693
TI  - Changes in Shoulder External Rotator Muscle Activity during Shoulder External
      Rotation in Various Arm Positions in the Sagittal Plane.
AB  - [Purpose] The aim of this study was to investigate changes in electromyographic
      (EMG) activity of the infraspinatus and posterior deltoid muscles during shoulder
      external rotation under different shoulder flexion angles. [Subjects] Thirteen
      participants were included in this study. [Methods] The participants performed
      isometric shoulder external rotation at 45 degrees , 90 degrees , and 135 degrees
      of shoulder flexion. A surface EMG system recorded the EMG activity of the
      infraspinatus and posterior deltoid muscles during shoulder external rotation.
      The changes in the muscle activity of infraspinatus and posterior deltoid and
      ratio of infraspinatus to posterior deltoid muscle activity were analyzed using
      one-way repeated-measures analysis of variance with Bonferroni's correction.
      [Results] The posterior deltoid activity was significantly decreased, while the
      ratio of the infraspinatus to posterior deltoid activity was significantly
      increased at 45 degrees  of shoulder flexion compared with 90 degrees  and 135
      degrees  of shoulder flexion (p < 0.05). There were no significant differences in
      the EMG activity of the infraspinatus among the three conditions (p > 0.05).
      [Conclusion] These findings indicate that shoulder external rotation at 45
      degrees  of shoulder flexion effectively reduced the contribution of the
      posterior deltoid activation to shoulder external rotation. 

PMID- 24567694
TI  - The Effectiveness of Thai Exercise with Traditional Massage on the Pain, Walking
      Ability and QOL of Older People with Knee Osteoarthritis: A Randomized Controlled
      Trial in the Community.
AB  - [Purpose] This study investigated the effectiveness of a class- and home-based
      exercise with massage between Thai traditional and standardized physical therapy
      (TPT and SPT) in older people with knee osteoarthritis (KOA). [Subjects and
      Methods] Thirty-one subjects with KOA (aged 50-85 years) in two selected villages
      were randomly assigned into the TPT or SPT programs. Seventeen TPT subjects
      received Thai exercise with traditional massage, and 14 SPT individuals performed
      strengthening exercise with Swedish massage. Both programs consisted of a class
      with supervision plus home self-care for 8 weeks; the subjects then managed home
      self-care for 1 year. [Results] After 2 months, the six-minute walk test (6MWT),
      Western Ontario and McMaster Universities Arthritis Index (WOMAC), and SF-36
      testing showed significant improvement in both groups, but the improvement of the
      TPT group was greater. After 1year, only the score for the 6MWT was greater in
      the TPT group than in the SPT group. [Conclusion] The TPT program yielded better
      results for the 6MWT, but, both programs had beneficial effects on the pain,
      function, and QOL of middle-aged and older patients with KOA in the community
      setting. 

PMID- 24567696
TI  - Effects of bilateral passive range of motion exercise on the function of upper
      extremities and activities of daily living in patients with acute stroke.
AB  - [Purpose] To evaluate the effects of early passive range of motion exercise on
      the function of upper extremities and activities of daily living in patients with
      acute stroke. [Methods] A total of 37 patients with acute stroke in intensive
      care units, were assigned to the experimental group (n=19) and control group
      (n=18). The experimental group performed passive range of motion exercise twice a
      day, for 4 weeks, immediately after a pretest; the patients in the control group
      performed the range of motion exercise in the same manner for 2 weeks beginning 2
      weeks after the pretest. The functions of upper extremities (edema, range of
      motion), manual function, and activities of daily living of both groups were
      measured before and at four weeks after the intervention. [Results] The
      experimental group showed a significant decrease in the edema of upper
      extremities compared with the control group. It also showed a significant
      increase in the range of motion, function of upper extremities, and the
      activities of daily living compared to the control group. [Conclusion] Passive
      range of motion exercise in the early stage can improve the function of upper
      extremities and activities of daily living in patients with acute stroke. 

PMID- 24567695
TI  - Effect of the modulation of optic flow speed on gait parameters in children with
      hemiplegic cerebral palsy.
AB  - [Purpose] We investigated the effects of modulation of the optic flow speed on
      gait parameters in children with hemiplegic cerebral palsy. [Methods] We examined
      10 children with hemiplegic cerebral palsy. The children underwent gait analysis
      under 3 different conditions of optic flow speed: slow, normal, and fast optic
      flow speed. The children walked across the walkway of a GAITRite system, while
      watching a virtual reality screen, and walking velocity, cadence, stride length,
      step length, single support time, and double support time were recorded.
      [Results] Compared with the other applied flow speed conditions, the fast optic
      flow speed (2 times the normal speed) significantly increased walking velocity,
      cadence, normalized step length, base of support, and single support cycle of
      both the paretic and non-paretic lower limbs. Moreover, compared with the other
      applied flow speed conditions, the slow optic flow speed (0.25 times the normal
      speed) yielded a significantly decreased walking velocity, cadence, normalized
      step length, base of support, and single support cycle for both the paretic and
      non-paretic lower limbs. [Conclusion] The gait parameters of children with
      hemiplegic cerebral palsy are altered by modulation of the optic flow speed.
      Thus, we believe that gait training involving modulation of the optic flow speed
      is feasible and suitable for resolving abnormal gait patterns in children with
      hemiplegic cerebral palsy. 

PMID- 24567697
TI  - The effect of abdominal bracing in combination with low extremity movements on
      changes in thickness of abdominal muscles and lumbar strength for low back pain.
AB  - [Purpose] The purpose of this study was to investigate the effects of abdominal
      bracing with low extremity movement on changes in thickness of abdominal muscles
      and lumbar strength. [Subjects] Sixteen patients with chronic low back pain were
      randomly assigned to two groups: an abdominal bracing with active straight leg
      raise (ABSLR) group and abdominal bracing with ankle dorsiflexion (ABDF) group.
      [Methods] All subjects were evaluated for their abdominal muscle strength using a
      MedX Lumbar Extension Machine and thickness of external oblique (EO), internal
      oblique (IO), and transverse abdominis (TrA) muscles using rehabilitative
      ultrasound imaging. Subjects in both groups were instructed to perform Abdominal
      bracing (AB). Simultaneously, those in the ABSLR group performed active SLR, and
      those in the ABDF group performed ankle dorsiflexion. [Results] In comparison
      between the ABSLR and ABDF groups, significant differences in the thickness of
      the IO and TrA muscles were observed after the intervention in the ABSLR group.
      Also, lumbar strength was showed a significant increase in both groups after
      interventions. [Conclusion] The results of this study demonstrated that ABSLR is
      a more effective method than ABDF for improvement of abdominal stabilization by
      increasing the thicknesses of the TrA and IO. 

PMID- 24567698
TI  - The effect of low extremity plyometric training on back muscle power of high
      school throwing event athletes.
AB  - [Purpose] The physical strength elements required for athletic throwing events
      include muscle strength, swiftness, agility, speed, flexibility, and physical
      balance. Although plyometric training and weight training are implemented as
      representative training methods for improving swiftness and agility, most studies
      of it have been conducted with players of other sports. [Subjects] The study
      subjects were 10 throwing event athletes attending K physical education high
      school. The subjects were randomly assigned to a control group of five subjects
      and an experimental group of five subjects. To analyze the body composition, an
      Inbody 3.0 instrument (Biospace, Korea) was used as experimental equipment to
      measure heights, weight, body fat percentages, and muscle masses and a Biodex
      system 4.0 (BIODEX, USA) was used to measure isokinetic muscle-joint and lumbar
      muscle strengths. The plyometric training consisted of 15 techniques out of the
      training methods introduced in the 'Power up plyometric training'. The plyometric
      program was implemented without any training load three times per week during
      daybreak exercises for the experimental group. The number of times and the number
      of sets were changed over time as follows: three sets of 10 times in the 1st -4th
      weeks, three sets of 15 times in the 5th-8th weeks, and five sets of 15 times in
      the 9th-12th weeks. [Results] According to the ANCOVA results of lumbar extensor
      muscle strength at 60 degrees /sec, the overall reliability of the model was
      significant. According to the ANCOVA results of lumbar flexor muscle strength at
      60 degrees /sec, the overall reliability of the model was significant.
      [Conclusion] Plyometric training positively affected high school throwing event
      athletes. To summarize the study findings, the application of plyometric training
      with high intensity and loads improved the results of athletes who perform highly
      intensive exercises at normal times. 

PMID- 24567699
TI  - Rare Variant of Vastus Medialis Detected in vivo by Ultrasound and Confirmed by
      High-resolution MRI.
AB  - [Purpose] This report describes an unusual incidental finding during ultrasound
      investigation of the vastus medialis muscle. Volunteers underwent ultrasound
      scanning as part of an on-going investigation into the architecture of the vastus
      medialis muscle. [Subjects and Methods] The distal thighs of forty-one subjects
      were scanned using the Philips iU22 US system. An unusual muscle morphology was
      detected bilaterally in one subject, who then underwent a 3T Magnetic Resonance
      Imaging (MRI) scan in order to further investigate the muscle morphology. The
      subject in question was a 32 year-old female who suffers from recurrent bilateral
      patellar dislocations. [Results] The MRI scan confirmed the ultrasound findings,
      and indicated the presence of the vastus medialis in two layers, with the VML
      continuing deep, separate from the VMO. [Conclusion] Although this rare variant
      has been been reported in previous cadaveric studies, we believe this to be the
      first report in the literature of this morphology in vivo. The biomechanical
      implications of this muscle arrangement are unknown, but it may not be without
      significance that this individual suffers from recurrent patellar dislocations. 

PMID- 24567700
TI  - Capacity building and collaborative research on cross-national studies in the
      Asian region.
AB  - To build capacity and collaborative research for future cross-national studies in
      the Asian and Pacific Islander (API) region, priority research topics were
      identified and discussed at the April 2013 Conference to Promote Global Health in
      Taipei. These topics included (1) Neuroscience on HIV/HCV and amphetamine-type
      stimulants (ATS), led by Drs. Linda Chang, Gene-Jack Wang, and Betty Tai; (2) ATS
      and mental health disorders, led by Drs. Richard Rawson and Wilson Compton; and
      (3) HIV/HCV transmission and social networks, led by Drs. Steven Shoptaw and
      Jacques Normand. Potential genetic studies spanning these topical areas as well
      as the importance of smoking cessation were further discussed, led by Dr. Ming
      Li. Additional priority research topics were also identified: (4) Drug use
      prevention, and (5) Family involvement to improve treatment adherence and
      recovery. Workgroups on these topics will be formed to prioritize research
      questions within the respective topical area and to determine the next steps. The
      ultimate goal of these workgroups is to stimulate collaboration that will
      eventually lead to research studies addressing critical issues related to the
      rising substance abuse and HIV infection rates in many Asian countries and, at
      the same time, to advance the scientific knowledge of substance abuse and HIV
      infection.

PMID- 24567701
TI  - Kynurenines in CNS disease: regulation by inflammatory cytokines.
AB  - The kynurenine pathway (KP) metabolizes the essential amino acid tryptophan and
      generates a number of neuroactive metabolites collectively called the
      kynurenines. Segregated into at least two distinct branches, often termed the
      "neurotoxic" and "neuroprotective" arms of the KP, they are regulated by the two
      enzymes kynurenine 3-monooxygenase and kynurenine aminotransferase, respectively.
      Interestingly, several enzymes in the pathway are under tight control of
      inflammatory mediators. Recent years have seen a tremendous increase in our
      understanding of neuroinflammation in CNS disease. This review will focus on the
      regulation of the KP by inflammatory mediators as it pertains to
      neurodegenerative and psychiatric disorders. 

PMID- 24567704
TI  - Volitional enhancement of firing synchrony and oscillation by neuronal operant
      conditioning: interaction with neurorehabilitation and brain-machine interface.
AB  - In this review, we focus on neuronal operant conditioning in which increments in
      neuronal activities are directly rewarded without behaviors. We discuss the
      potential of this approach to elucidate neuronal plasticity for enhancing
      specific brain functions and its interaction with the progress in
      neurorehabilitation and brain-machine interfaces. The key to-be-conditioned
      activities that this paper emphasizes are synchronous and oscillatory firings of
      multiple neurons that reflect activities of cell assemblies. First, we introduce
      certain well-known studies on neuronal operant conditioning in which conditioned
      enhancements of neuronal firing were reported in animals and humans. These
      studies demonstrated the feasibility of volitional control over neuronal
      activity. Second, we refer to the recent studies on operant conditioning of
      synchrony and oscillation of neuronal activities. In particular, we introduce a
      recent study showing volitional enhancement of oscillatory activity in monkey
      motor cortex and our study showing selective enhancement of firing synchrony of
      neighboring neurons in rat hippocampus. Third, we discuss the reasons for
      emphasizing firing synchrony and oscillation in neuronal operant conditioning,
      the main reason being that they reflect the activities of cell assemblies, which
      have been suggested to be basic neuronal codes representing information in the
      brain. Finally, we discuss the interaction of neuronal operant conditioning with
      neurorehabilitation and brain-machine interface (BMI). We argue that synchrony
      and oscillation of neuronal firing are the key activities required for developing
      both reliable neurorehabilitation and high-performance BMI. Further, we conclude
      that research of neuronal operant conditioning, neurorehabilitation, BMI, and
      system neuroscience will produce findings applicable to these interrelated
      fields, and neuronal synchrony and oscillation can be a common important bridge
      among all of them. 

PMID- 24567702
TI  - Presynaptic [Ca(2+)] and GCAPs: aspects on the structure and function of
      photoreceptor ribbon synapses.
AB  - Changes in intracellular calcium ions [Ca(2+)] play important roles in
      photoreceptor signaling. Consequently, intracellular [Ca(2+)] levels need to be
      tightly controlled. In the light-sensitive outer segments (OS) of photoreceptors,
      Ca(2+) regulates the activity of retinal guanylate cyclases thus playing a
      central role in phototransduction and light-adaptation by restoring light-induced
      decreases in cGMP. In the synaptic terminals, changes of intracellular Ca(2+)
      trigger various aspects of neurotransmission. Photoreceptors employ tonically
      active ribbon synapses that encode light-induced, graded changes of membrane
      potential into modulation of continuous synaptic vesicle exocytosis. The active
      zones of ribbon synapses contain large electron-dense structures, synaptic
      ribbons, that are associated with large numbers of synaptic vesicles. Synaptic
      coding at ribbon synapses differs from synaptic coding at conventional (phasic)
      synapses. Recent studies revealed new insights how synaptic ribbons are involved
      in this process. This review focuses on the regulation of [Ca(2+)] in presynaptic
      photoreceptor terminals and on the function of a particular Ca(2+)-regulated
      protein, the neuronal calcium sensor protein GCAP2 (guanylate cyclase-activating
      protein-2) in the photoreceptor ribbon synapse. GCAP2, an EF-hand-containing
      protein plays multiple roles in the OS and in the photoreceptor synapse. In the
      OS, GCAP2 works as a Ca(2+)-sensor within a Ca(2+)-regulated feedback loop that
      adjusts cGMP levels. In the photoreceptor synapse, GCAP2 binds to RIBEYE, a
      component of synaptic ribbons, and mediates Ca(2+)-dependent plasticity at that
      site. Possible mechanisms are discussed. 

PMID- 24567705
TI  - Acute ethanol exposure inhibits silencing of cerebellar Golgi cell firing induced
      by granule cell axon input.
AB  - Golgi cells (GoCs) are specialized interneurons that provide inhibitory input to
      granule cells in the cerebellar cortex. GoCs are pacemaker neurons that
      spontaneously fire action potentials, triggering spontaneous inhibitory
      postsynaptic currents in granule cells and also contributing to the generation
      tonic GABAA receptor-mediated currents in granule cells. In turn, granule cell
      axons provide feedback glutamatergic input to GoCs. It has been shown that high
      frequency stimulation of granule cell axons induces a transient pause in GoC
      firing in a type 2-metabotropic glutamate receptor (mGluR2)-dependent manner.
      Here, we investigated the effect ethanol on the pause of GoC firing induced by
      high frequency stimulation of granule cell axons. GoC electrophysiological
      recordings were performed in parasagittal cerebellar vermis slices from postnatal
      day 23 to 26 rats. Loose-patch cell-attached recordings revealed that ethanol (40
      mM) reversibly decreases the pause duration. An antagonist of mGluR2 reduced the
      pause duration but did not affect the effect of ethanol. Whole-cell voltage-clamp
      recordings showed that currents evoked by an mGluR2 agonist were not
      significantly affected by ethanol. Perforated-patch experiments in which
      hyperpolarizing and depolarizing currents were injected into GoCs demonstrated
      that there is an inverse relationship between spontaneous firing and pause
      duration. Slight inhibition of the Na(+)/K(+) pump mimicked the effect of ethanol
      on pause duration. In conclusion, ethanol reduces the granule cell axon-mediated
      feedback mechanism by reducing the input responsiveness of GoCs. This would
      result in a transient increase of GABAA receptor-mediated inhibition of granule
      cells, limiting information flow at the input stage of the cerebellar cortex. 

PMID- 24567706
TI  - Deletion of the forebrain mineralocorticoid receptor impairs social
      discrimination and decision-making in male, but not in female mice.
AB  - Social interaction with unknown individuals requires fast processing of
      information to decide whether it is friend or foe. This process of discrimination
      and decision-making is stressful and triggers secretion of corticosterone
      activating mineralocorticoid receptor (MR) and glucocorticoid receptor (GR). The
      MR is involved in appraisal of novel experiences and risk assessment. Recently,
      we have demonstrated in a dual-solution memory task that MR plays a role in the
      early stage of information processing and decision-making. Here we examined
      social approach and social discrimination in male and female mice lacking MR from
      hippocampal-amygdala-prefrontal circuitry and controls. The social approach task
      allows the assessment of time spent with an unfamiliar mouse and the ability to
      discriminate between familiar and unfamiliar conspecifics. The male and female
      test mice were both more interested in the social than the non-social experience
      and deletion of their limbic MR increased the time spent with an unfamiliar
      mouse. Unlike controls, the male MR(CaMKCre) mice were not able to discriminate
      between an unfamiliar and the familiar mouse. However, the female MR mutant had
      retained the discriminative ability between unfamiliar and familiar mice.
      Administration of the MR antagonist RU28318 to male mice supported the role of
      the MR in the discrimination between an unfamiliar mouse and a non-social
      stimulus. No effect was found with a GR antagonist. Our findings suggest that MR
      is involved in sociability and social discrimination in a sex-specific manner
      through inhibitory control exerted putatively via limbic-hippocampal efferents.
      The ability to discriminate between familiar and unfamiliar conspecifics is of
      uttermost importance for territorial defense and depends on a role of MR in
      decision-making. 

PMID- 24567703
TI  - Current view on the functional regulation of the neuronal K(+)-Cl(-)
      cotransporter KCC2.
AB  - In the mammalian central nervous system (CNS), the inhibitory strength of
      chloride (Cl(-))-permeable GABAA and glycine receptors (GABAAR and GlyR) depends
      on the intracellular Cl(-) concentration ([Cl(-)]i). Lowering [Cl(-)]i enhances
      inhibition, whereas raising [Cl(-)]i facilitates neuronal activity. A neuron's
      basal level of [Cl(-)]i, as well as its Cl(-) extrusion capacity, is critically
      dependent on the activity of the electroneutral K(+)-Cl(-) cotransporter KCC2, a
      member of the SLC12 cation-Cl(-) cotransporter (CCC) family. KCC2 deficiency
      compromises neuronal migration, formation and the maturation of GABAergic and
      glutamatergic synaptic connections, and results in network hyperexcitability and
      seizure activity. Several neurological disorders including multiple epilepsy
      subtypes, neuropathic pain, and schizophrenia, as well as various insults such as
      trauma and ischemia, are associated with significant decreases in the Cl(-)
      extrusion capacity of KCC2 that result in increases of [Cl(-)]i and the
      subsequent hyperexcitability of neuronal networks. Accordingly, identifying the
      key upstream molecular mediators governing the functional regulation of KCC2, and
      modifying these signaling pathways with small molecules, might constitute a novel
      neurotherapeutic strategy for multiple diseases. Here, we discuss recent advances
      in the understanding of the mechanisms regulating KCC2 activity, and of the role
      these mechanisms play in neuronal Cl(-) homeostasis and GABAergic
      neurotransmission. As KCC2 mediates electroneutral transport, the experimental
      recording of its activity constitutes an important research challenge; we
      therefore also, provide an overview of the different methodological approaches
      utilized to monitor function of KCC2 in both physiological and pathological
      conditions. 

PMID- 24567707
TI  - Difficulty leading interpersonal coordination: towards an embodied signature of
      social anxiety disorder.
AB  - Defined by a persistent fear of embarrassment or negative evaluation while
      engaged in social interaction or public performance, social anxiety disorder
      (SAD) is one of the most common psychiatric syndromes. Previous research has made
      a considerable effort to better understand and assess this mental disorder.
      However, little attention has been paid to social motor behavior of patients with
      SAD despite its crucial importance in daily social interactions. Previous
      research has shown that the coordination of arm, head or postural movements of
      interacting people can reflect their mental states or feelings such as social
      connectedness and social motives, suggesting that interpersonal movement
      coordination may be impaired in patients suffering from SAD. The current study
      was specifically aimed at determining whether SAD affects the dynamics of social
      motor coordination. We compared the unintentional and intentional rhythmic
      coordination of a SAD group (19 patients paired with control participants) with
      the rhythmic coordination of a control group (19 control pairs) in an
      interpersonal pendulum coordination task. The results demonstrated that
      unintentional social motor coordination was preserved with SAD while intentional
      coordination was impaired. More specifically, intentional coordination became
      impaired when patients with SAD had to lead the coordination as indicated by
      poorer (i.e., more variable) coordination. These differences between intentional
      and unintentional coordination as well as between follower and leader roles
      reveal an impaired coordination dynamics that is specific to SAD, and thus, opens
      promising research directions to better understand, assess and treat this mental
      disorder. 

PMID- 24567708
TI  - Social information and personal interests modulate neural activity during
      economic decision-making.
AB  - In the present study we employed electrophysiological recordings to investigate
      the levels of processing at which positive and negative descriptions of other
      people bias social decision-making in a game in which participants accepted or
      rejected economic offers. Besides social information, we manipulated the fairness
      of the assets distribution, whether offers were advantageous or not for the
      participant and the uncertainty of the game context. Results show that a negative
      description of the interaction partner enhanced the medial frontal negativity
      (MFN) in an additive manner with fairness evaluations. The description of the
      partner interacted with personal benefit considerations, showing that this
      positive or negative information only biased the evaluation of offers when they
      did not favor the participant. P300 amplitudes were enhanced by advantageous
      offers, suggesting their heightened motivational significance at later stages of
      processing. Throughout all stages, neural activity was enhanced with certainty
      about the personal assignments of the split. These results provide new evidence
      on the importance of interpersonal information and considerations of self
      interests relative to others in decision-making situations. 

PMID- 24567710
TI  - Replication of the correlation between natural mood states and working memory
      related prefrontal activity measured by near-infrared spectroscopy in a German
      sample.
AB  - Previous studies have suggested complex interactions of mood and cognition in the
      lateral prefrontal cortex (PFC). Although such interactions might be influenced
      by various factors such as personality and cultural background, their
      reproducibility and generalizability have hardly been explored. In the present
      study, we focused on a previously found correlation between negative mood states
      and PFC activity during a verbal working memory (WM) task, which had been
      demonstrated by using near-infrared spectroscopy (NIRS) in a Japanese sample. To
      confirm and extend the generalizability of this finding, we conducted a similar
      experiment in a German sample, i.e., participants with a different language
      background. Here, PFC activity during verbal and spatial WM tasks was measured by
      NIRS using a delayed match-to-sample paradigm after the participants' natural
      mood states had been evaluated by a mood questionnaire (Profiles of Mood States:
      POMS). We also included control tasks to consider the general effect of
      visual/auditory inputs and motor responses. For the verbal WM task, the POMS
      total mood disturbance (TMD) score was negatively correlated with baseline
      corrected NIRS data mainly over the left dorsolateral PFC (i.e., higher TMD
      scores were associated with reduced activation), which is consistent with
      previous studies. Moreover, this relationship was also present when verbal WM
      activation was contrasted with the control task. These results suggest that the
      mood-cognition interaction within the PFC is reproducible in a sample with a
      different language background and represents a general phenomenon. 

PMID- 24567711
TI  - Differences in neural connectivity between the substantia nigra and ventral
      tegmental area in the human brain.
AB  - OBJECTIVES: Many animal and a few human studies have reported on the neural
      connectivity of the substantia nigra (SN) and the ventral tegmental area (VTA).
      However, it has not been clearly elucidated so far. We attempted to investigate
      any differences in neural connectivity of the SN/VTA in the human brain, using
      diffusion tensor imaging (DTI). METHODS: Sixty-three healthy subjects were
      recruited for this study. DTIs were acquired using a sensitivity-encoding head
      coil at 1. 5T. Connectivity was defined as the incidence of connection between
      the SN/VTA and each brain regions in the brain. RESULTS: The connectivity of SN
      was higher than that of the VTA. This included in the primary motor cortex,
      primary somatosensory cortex, premotor cortex, prefrontal cortex, caudate
      nucleus, globus pallidus, putamen, nucleus accumbens, temporal lobe, amygdala,
      pontine basis, occipital lobe, anterior and posterior lobe of cerebellum, corpus
      callosum, and external capsule (p < 0.05). However, no significant differences
      were observed in the red nucleus, thalamus, pontine tegmentum, and medial
      temporal lobe between the SN and VTA (p > 0.05). CONCLUSIONS: We found the
      differences in neural connectivity of the SN/VTA in the human brain. The method
      and results of this study can provide useful information for clinicians and
      researchers in neuroscience, especially who work for Parkinson's disease and
      patients with brain injury.

PMID- 24567709
TI  - Arousal and attention re-orienting in autism spectrum disorders: evidence from
      auditory event-related potentials.
AB  - The extended phenotype of autism spectrum disorders (ASD) includes a combination
      of arousal regulation problems, sensory modulation difficulties, and attention re
      orienting deficit. A slow and inefficient re-orienting to stimuli that appear
      outside of the attended sensory stream is thought to be especially detrimental
      for social functioning. Event-related potentials (ERPs) and magnetic fields
      (ERFs) may help to reveal which processing stages underlying brain response to
      unattended but salient sensory event are affected in individuals with ASD.
      Previous research focusing on two sequential stages of the brain response
      automatic detection of physical changes in auditory stream, indexed by mismatch
      negativity (MMN), and evaluation of stimulus novelty, indexed by P3a component,
      found in individuals with ASD either increased, decreased, or normal processing
      of deviance and novelty. The review examines these apparently conflicting
      results, notes gaps in previous findings, and suggests a potentially unifying
      hypothesis relating the dampened responses to unattended sensory events to the
      deficit in rapid arousal process. Specifically, "sensory gating" studies focused
      on pre-attentive arousal consistently demonstrated that brain response to
      unattended and temporally novel sound in ASD is already affected at around 100 ms
      after stimulus onset. We hypothesize that abnormalities in nicotinic cholinergic
      arousal pathways, previously reported in individuals with ASD, may contribute to
      these ERP/ERF aberrations and result in attention re-orienting deficit. Such
      cholinergic dysfunction may be present in individuals with ASD early in life and
      can influence both sensory processing and attention re-orienting behavior.
      Identification of early neurophysiological biomarkers for cholinergic deficit
      would help to detect infants "at risk" who can potentially benefit from
      particular types of therapies or interventions. 

PMID- 24567712
TI  - Mathematical difficulties as decoupling of expectation and developmental
      trajectories.
AB  - Recent years have seen an increase in research articles and reviews exploring
      mathematical difficulties (MD). Many of these articles have set out to explain
      the etiology of the problems, the possibility of different subtypes, and
      potential brain regions that underlie many of the observable behaviors. These
      articles are very valuable in a research field, which many have noted, falls
      behind that of reading and language disabilities. Here will provide a perspective
      on the current understanding of MD from a different angle, by outlining the
      school curriculum of England and the US and connecting these to the skills needed
      at different stages of mathematical understanding. We will extend this to explore
      the cognitive skills which most likely underpin these different stages and whose
      impairment may thus lead to mathematics difficulties at all stages of mathematics
      development. To conclude we will briefly explore interventions that are currently
      available, indicating whether these can be used to aid the different children at
      different stages of their mathematical development and what their current
      limitations may be. The principal aim of this review is to establish an explicit
      connection between the academic discourse, with its research base and concepts,
      and the developmental trajectory of abstract mathematical skills that is expected
      (and somewhat dictated) in formal education. This will possibly help to highlight
      and make sense of the gap between the complexity of the MD range in real life and
      the state of its academic science. 

PMID- 24567713
TI  - Motor empathy is a consequence of misattribution of sensory information in
      observers.
AB  - Human behavior depends crucially on the ability to interact with others and
      empathy has a critical role in enabling this to occur effectively. This can be an
      unconscious process and based on natural instinct and inner imitation (Montag et
      al., 2008) responding to observed and executed actions (Newman-Norlund et al.,
      2007). Motor empathy relating to painful stimuli is argued to occur via the
      mirror system in motor areas (Rizzolatti and Luppino, 2001). Here we investigated
      the effects of the location of emotional information on the responses of this
      system. Motor evoked potential (MEP) amplitudes from the right first dorsal
      interosseus (FDI) muscle in the hand elicited by single pulses of transcranial
      magnetic stimulation (TMS) delivered over the left motor cortex were measured
      while participants observed a video of a needle entering a hand over the FDI
      muscle, representing a painful experience for others. To maintain subjects'
      internal representation across different viewing distances, we used the same size
      of hand stimuli both in peripersonal and extrapersonal space. We found a reduced
      MEP response, indicative of inhibition of the corticospinal system, only for
      stimuli presented in peripersonal space and not in extrapersonal space. This
      empathy response only occurring for near space stimuli suggests that it may be a
      consequence of misidentification of sensory information as being directly related
      to the observer. A follow up experiment confirmed that the effect was not a
      consequence of the size of the stimuli presented, in agreement with the
      importance of the near space/far space boundary for misattribution of body
      related information. This is consistent with the idea that empathy is, at least
      partially, a consequence of misattribution of perceptual information relating to
      another to the observer and that pain perception is modulated by the nature of
      perception of the pain. 

PMID- 24567714
TI  - Parameters for burst detection.
AB  - Bursts of action potentials within neurons and throughout networks are believed
      to serve roles in how neurons handle and store information, both in vivo and in
      vitro. Accurate detection of burst occurrences and durations are therefore
      crucial for many studies. A number of algorithms have been proposed to do so, but
      a standard method has not been adopted. This is due, in part, to many algorithms
      requiring the adjustment of multiple ad-hoc parameters and further post-hoc
      criteria in order to produce satisfactory results. Here, we broadly catalog
      existing approaches and present a new approach requiring the selection of only a
      single parameter: the number of spikes N comprising the smallest burst to
      consider. A burst was identified if N spikes occurred in less than T ms, where
      the threshold T was automatically determined from observing a probability
      distribution of inter-spike-intervals. Performance was compared vs. different
      classes of detectors on data gathered from in vitro neuronal networks grown over
      microelectrode arrays. Our approach offered a number of useful features
      including: a simple implementation, no need for ad-hoc or post-hoc criteria, and
      precise assignment of burst boundary time points. Unlike existing approaches,
      detection was not biased toward larger bursts, allowing identification and
      analysis of a greater range of neuronal and network dynamics. 

PMID- 24567716
TI  - Bifurcation analysis of "synchronization fluctuation": a diagnostic measure of
      brain epileptic states.

PMID- 24567715
TI  - When do microcircuits produce beyond-pairwise correlations?
AB  - Describing the collective activity of neural populations is a daunting task.
      Recent empirical studies in retina, however, suggest a vast simplification in how
      multi-neuron spiking occurs: the activity patterns of retinal ganglion cell (RGC)
      populations under some conditions are nearly completely captured by pairwise
      interactions among neurons. In other circumstances, higher-order statistics are
      required and appear to be shaped by input statistics and intrinsic circuit
      mechanisms. Here, we study the emergence of higher-order interactions in a model
      of the RGC circuit in which correlations are generated by common input. We
      quantify the impact of higher-order interactions by comparing the responses of
      mechanistic circuit models vs. "null" descriptions in which all higher-than
      pairwise correlations have been accounted for by lower order statistics; these
      are known as pairwise maximum entropy (PME) models. We find that over a broad
      range of stimuli, output spiking patterns are surprisingly well captured by the
      pairwise model. To understand this finding, we study an analytically tractable
      simplification of the RGC model. We find that in the simplified model, bimodal
      input signals produce larger deviations from pairwise predictions than unimodal
      inputs. The characteristic light filtering properties of the upstream RGC
      circuitry suppress bimodality in light stimuli, thus removing a powerful source
      of higher-order interactions. This provides a novel explanation for the
      surprising empirical success of pairwise models. 

PMID- 24567717
TI  - Multi-atlas segmentation of subcortical brain structures via the AutoSeg software
      pipeline.
AB  - Automated segmenting and labeling of individual brain anatomical regions, in MRI
      are challenging, due to the issue of individual structural variability. Although
      atlas-based segmentation has shown its potential for both tissue and structure
      segmentation, due to the inherent natural variability as well as disease-related
      changes in MR appearance, a single atlas image is often inappropriate to
      represent the full population of datasets processed in a given neuroimaging
      study. As an alternative for the case of single atlas segmentation, the use of
      multiple atlases alongside label fusion techniques has been introduced using a
      set of individual "atlases" that encompasses the expected variability in the
      studied population. In our study, we proposed a multi-atlas segmentation scheme
      with a novel graph-based atlas selection technique. We first paired and co
      registered all atlases and the subject MR scans. A directed graph with edge
      weights based on intensity and shape similarity between all MR scans is then
      computed. The set of neighboring templates is selected via clustering of the
      graph. Finally, weighted majority voting is employed to create the final
      segmentation over the selected atlases. This multi-atlas segmentation scheme is
      used to extend a single-atlas-based segmentation toolkit entitled AutoSeg, which
      is an open-source, extensible C++ based software pipeline employing BatchMake for
      its pipeline scripting, developed at the Neuro Image Research and Analysis
      Laboratories of the University of North Carolina at Chapel Hill. AutoSeg performs
      N4 intensity inhomogeneity correction, rigid registration to a common template
      space, automated brain tissue classification based skull-stripping, and the multi
      atlas segmentation. The multi-atlas-based AutoSeg has been evaluated on
      subcortical structure segmentation with a testing dataset of 20 adult brain MRI
      scans and 15 atlas MRI scans. The AutoSeg achieved mean Dice coefficients of
      81.73% for the subcortical structures. 

PMID- 24567718
TI  - The effects of odor and body posture on perceived duration.
AB  - This study reports an examination of the internal clock model, according to which
      subjective time duration is influenced by attention and arousal state. In a time
      production task, we examine the hypothesis that an arousing odor and an upright
      body posture affect perceived duration. The experimental task was performed while
      participants were exposed to an odor and either sitting upright (arousing
      condition) or lying down in a relaxing chair (relaxing condition). They were
      allocated to one of three experimental odor conditions: rosemary (arousing
      condition), peppermint (relaxing condition), and no odor (control condition). The
      predicted effects of the odors were not borne out by the results. Self-reported
      arousal (SRA) and pleasure (PL) states were measured before, during (after each
      body posture condition) and postexperimentally. Heart rate (HR) and skin
      conductance were measured before and during the experiment. As expected, odor had
      an effect on perceived duration. When participants were exposed to rosemary odor,
      they produced significantly shorter time intervals than in the no odor condition.
      This effect, however, could not be explained by increased arousal. There was no
      effect of body posture on perceived duration, even though body posture did induce
      arousal. The results do not support the proposed arousal mechanism of the
      internal clock model. 

PMID- 24567719
TI  - Chemogenomics knowledgebased polypharmacology analyses of drug abuse related G
      protein coupled receptors and their ligands.
AB  - Drug abuse (DA) and addiction is a complex illness, broadly viewed as a
      neurobiological impairment with genetic and environmental factors that influence
      its development and manifestation. Abused substances can disrupt the activity of
      neurons by interacting with many proteins, particularly G-protein coupled
      receptors (GPCRs). A few medicines that target the central nervous system (CNS)
      can also modulate DA related proteins, such as GPCRs, which can act in
      conjunction with the controlled psychoactive substance(s) and increase side
      effects. To fully explore the molecular interaction networks that underlie DA and
      to effectively modulate the GPCRs in these networks with small molecules for DA
      treatment, we built a drug-abuse domain specific chemogenomics knowledgebase (DA
      KB) to centralize the reported chemogenomics research information related to DA
      and CNS disorders in an effort to benefit researchers across a broad range of
      disciplines. We then focus on the analysis of GPCRs as many of them are closely
      related with DA. Their distribution in human tissues was also analyzed for the
      study of side effects caused by abused drugs. We further implement our
      computational algorithms/tools to explore DA targets, DA mechanisms and pathways
      involved in polydrug addiction and to explore polypharmacological effects of the
      GPCR ligands. Finally, the polypharmacology effects of GPCRs-targeted medicines
      for DA treatment were investigated and such effects can be exploited for the
      development of drugs with polypharmacophore for DA intervention. The
      chemogenomics database and the analysis tools will help us better understand the
      mechanism of drugs abuse and facilitate to design new medications for system
      pharmacotherapy of DA. 

PMID- 24567720
TI  - Safety, tolerability, and biomarkers of the treatment of mice with aerosolized
      Toll-like receptor ligands.
AB  - We have previously discovered a synergistically therapeutic combination of two
      Toll-like receptor ligands, an oligodeoxynucleotide (ODN) and Pam2CSK4.
      Aerosolization of these ligands stimulates innate immunity within the lungs to
      prevent pneumonia from bacterial and viral pathogens. Here we examined the safety
      and tolerability of this treatment in mice, and characterized the expression of
      biomarkers of innate immune activation. We found that neutrophils appeared in
      lung lavage fluid 4 h after treatment, reached a peak at 48 h, and resolved by 7
      days. The peak of neutrophil influx was accompanied by a small increase in lung
      permeability. Despite the abundance of neutrophils in lung lavage fluid, only
      rare neutrophils were visible histopathologically in the interstitium surrounding
      bronchi and veins and none were visible in alveolar airspaces. The cytokines
      interleukin 6 (IL-6), tumour necrosis factor, and Chemokine (C-X-C motif) ligand
      2 rose several hundred-fold in lung lavage fluid 4 h after treatment in a dose
      dependent and synergistic manner, providing useful biomarkers of lung activation.
      IL-6 rose fivefold in serum with delayed kinetics compared to its rise in lavage
      fluid, and might serve as a systemic biomarker of immune activation of the lungs.
      The dose-response relationship of lavage fluid cytokines was preserved in mice
      that underwent myeloablative treatment with cytosine arabinoside to model the
      treatment of hematologic malignancy. There were no overt signs of distress in
      mice treated with ODN/Pam2CSK4 in doses up to eightfold the therapeutic dose, and
      no changes in temperature, respiratory rate, or behavioral signs of sickness
      including sugar water preference, food disappearance, cage exploration or social
      interaction, though there was a small degree of transient weight loss. We
      conclude that treatment with aerosolized ODN/Pam2CSK4 is well tolerated in mice,
      and that innate immune activation of the lungs can be monitored by the
      measurement of inflammatory cytokines in lung lavage fluid and serum. 

PMID- 24567723
TI  - A dynamically minimalist cognitive explanation of musical preference: is
      familiarity everything?
AB  - This paper examines the idea that attraction to music is generated at a cognitive
      level through the formation and activation of networks of interlinked "nodes."
      Although the networks involved are vast, the basic mechanism for activating the
      links is relatively simple. Two comprehensive cognitive-behavioral models of
      musical engagement are examined with the aim of identifying the underlying
      cognitive mechanisms and processes involved in musical experience. A "dynamical
      minimalism" approach (after Nowak, 2004) is applied to re-interpret musical
      engagement (listening, performing, composing, or imagining any of these) and to
      revise the latest version of the reciprocal-feedback model (RFM) of music
      processing. Specifically, a single cognitive mechanism of "spreading activation"
      through previously associated networks is proposed as a pleasurable outcome of
      musical engagement. This mechanism underlies the dynamic interaction of the
      various components of the RFM, and can thereby explain the generation of positive
      affects in the listener's musical experience. This includes determinants of that
      experience stemming from the characteristics of the individual engaging in the
      musical activity (whether listener, composer, improviser, or performer), the
      situation and contexts (e.g., social factors), and the music (e.g., genre,
      structural features). The theory calls for new directions for future research,
      two being (1) further investigation of the components of the RFM to better
      understand musical experience and (2) more rigorous scrutiny of common findings
      about the salience of familiarity in musical experience and preference. 

PMID- 24567721
TI  - Effects of cannabinoid drugs on the deficit of prepulse inhibition of startle in
      an animal model of schizophrenia: the SHR strain.
AB  - Clinical and neurobiological findings suggest that the cannabinoids and the
      endocannabinoid system may be implicated in the pathophysiology and treatment of
      schizophrenia. We described that the spontaneously hypertensive rats (SHR) strain
      presents a schizophrenia behavioral phenotype that is specifically attenuated by
      antipsychotic drugs, and potentiated by proschizophrenia manipulations. Based on
      these findings, we have suggested this strain as an animal model of
      schizophrenia. The aim of this study was to evaluate the effects of cannabinoid
      drugs on the deficit of prepulse inhibition (PPI) of startle, the main paradigm
      used to study sensorimotor gating impairment related to schizophrenia, presented
      by the SHR strain. The following drugs were used: (1) WIN55212,2 (cannabinoid
      agonist), (2) rimonabant (CB1 antagonist), (3) AM404 (anandamide uptake
      inhibitor), and (4) cannabidiol (CBD; indirect CB1/CB2 receptor antagonist, among
      other effects). Wistar rats (WRs) and SHRs were treated with vehicle (VEH) or
      different doses of WIN55212 (0.3, 1, or 3 mg/kg), rimonabant (0.75, 1.5, or 3
      mg/kg), AM404 (1, 5, or 10 mg/kg), or CBD (15, 30, or 60 mg/kg). VEH-treated SHRs
      showed a decreased PPI when compared to WRs. This PPI deficit was reversed by 1
      mg/kg WIN and 30 mg/kg CBD. Conversely, 0.75 mg/kg rimonabant decreased PPI in
      SHR strain, whereas AM404 did not modify it. Our results reinforce the role of
      the endocannabinoid system in the sensorimotor gating impairment related to
      schizophrenia, and point to cannabinoid drugs as potential therapeutic
      strategies. 

PMID- 24567722
TI  - A metabolic link to skeletal muscle wasting and regeneration.
AB  - Due to its essential role in movement, insulating the internal organs, generating
      heat to maintain core body temperature, and acting as a major energy storage
      depot, any impairment to skeletal muscle structure and function may lead to an
      increase in both morbidity and mortality. In the context of skeletal muscle,
      altered metabolism is directly associated with numerous pathologies and
      disorders, including diabetes, and obesity, while many skeletal muscle
      pathologies have secondary changes in metabolism, including cancer cachexia,
      sarcopenia and the muscular dystrophies. Furthermore, the importance of cellular
      metabolism in the regulation of skeletal muscle stem cells is beginning to
      receive significant attention. Thus, it is clear that skeletal muscle metabolism
      is intricately linked to the regulation of skeletal muscle mass and regeneration.
      The aim of this review is to discuss some of the recent findings linking a change
      in metabolism to changes in skeletal muscle mass, as well as describing some of
      the recent studies in developmental, cancer and stem-cell biology that have
      identified a role for cellular metabolism in the regulation of stem cell
      function, a process termed "metabolic reprogramming." 

PMID- 24567725
TI  - Modulation of visual attention by object affordance.
AB  - Some objects in our environment are strongly tied to motor actions, a phenomenon
      called object affordance. A cup, for example, affords us to reach out to it and
      grasp it by its handle. Studies indicate that merely viewing an affording object
      triggers motor activations in the brain. The present study investigated whether
      object affordance would also result in an attention bias, that is, whether
      observers would rather attend to graspable objects within reach compared to non
      graspable but reachable objects or to graspable objects out of reach. To this
      end, we conducted a combined reaction time and motion tracking study with a table
      in a virtual three-dimensional space. Two objects were positioned on the table,
      one near, the other one far from the observer. In each trial, two graspable
      objects, two non-graspable objects, or a combination of both was presented.
      Participants were instructed to detect a probe appearing on one of the objects as
      quickly as possible. Detection times served as indirect measure of attention
      allocation. The motor association with the graspable object was additionally
      enhanced by having participants grasp a real object in some of the trials. We
      hypothesized that visual attention would be preferentially allocated to the near
      graspable object, which should be reflected in reduced reaction times in this
      condition. Our results confirm this assumption: probe detection was fastest at
      the graspable object at the near position compared to the far position or to a
      non-graspable object. A follow-up experiment revealed that in addition to object
      affordance per se, immediate graspability of an affording object may also
      influence this near-space advantage. Our results suggest that visuospatial
      attention is preferentially allocated to affording objects which are immediately
      graspable, and thus establish a strong link between an object' s motor affordance
      and visual attention. 

PMID- 24567724
TI  - Guidance of visual attention by semantic information in real-world scenes.
AB  - Recent research on attentional guidance in real-world scenes has focused on
      object recognition within the context of a scene. This approach has been valuable
      for determining some factors that drive the allocation of visual attention and
      determine visual selection. This article provides a review of experimental work
      on how different components of context, especially semantic information, affect
      attentional deployment. We review work from the areas of object recognition,
      scene perception, and visual search, highlighting recent studies examining
      semantic structure in real-world scenes. A better understanding on how humans
      parse scene representations will not only improve current models of visual
      attention but also advance next-generation computer vision systems and human
      computer interfaces. 

PMID- 24567726
TI  - Pregnancy and olfaction: a review.
AB  - Many women report a heightened sense of smell during pregnancy. Accounts of these
      anecdotes have existed for over 100 years, but scientific evidence has been
      sparse and inconclusive. In this review, I examine the literature on olfactory
      perception during pregnancy including measures of self-report, olfactory
      thresholds, odor identification, intensity and hedonic ratings, and disgust.
      Support for a general decrease in olfactory thresholds (increase in sensitivity)
      is generally lacking. There is limited evidence that some suprathreshold measures
      of olfactory perception, such as hedonic ratings of odors, are affected by
      pregnancy, but these effects are idiosyncratic. In this review, I explore the
      hypotheses that have been put forth to explain changes in olfactory perception
      during pregnancy and provide suggestions for further research. 

PMID- 24567727
TI  - Vision affects tactile target and distractor processing even when space is task
      irrelevant.
AB  - The human brain is adapted to integrate the information from multiple sensory
      modalities into coherent, robust representations of the objects and events in the
      external world. A large body of empirical research has demonstrated the
      ubiquitous nature of the interactions that take place between vision and touch,
      with the former typically dominating over the latter. Many studies have
      investigated the influence of visual stimuli on the processing of tactile stimuli
      (and vice versa). Other studies, meanwhile, have investigated the effect of
      directing a participant's gaze either toward or else away from the body-part
      receiving the target tactile stimulation. Other studies, by contrast, have
      compared performance in those conditions in which the participant's eyes have
      been open versus closed. We start by reviewing the research that has been
      published to date demonstrating the influence of vision on the processing of
      tactile targets, that is, on those stimuli that have to be attended or responded
      to. We outline that many - but not all - of the visuotactile interactions that
      have been observed to date may be attributable to the direction of spatial
      attention. We then move on to focus on the crossmodal influence of vision, as
      well as of the direction of gaze, on the processing of tactile distractors. We
      highlight the results of those studies demonstrating the influence of vision,
      rather than gaze direction (i.e., the direction of overt spatial attention), on
      tactile distractor processing (e.g., tactile variants of the negative-priming or
      flanker task). The conclusion is that no matter how vision of a tactile
      distractor is engaged, the result would appear to be the same, namely that
      tactile distractors are processed more thoroughly. 

PMID- 24567730
TI  - Assessing the advantage of morphological changes in Candida albicans: a game
      theoretical study.
AB  - A range of attributes determines the virulence of human pathogens. During
      interactions with their hosts, pathogenic microbes often undergo transitions
      between distinct stages, and the ability to switch between these can be directly
      related to the disease process. Understanding the mechanisms and dynamics of
      these transitions is a key factor in understanding and combating infectious
      diseases. The human fungal pathogen Candida albicans exhibits different
      morphotypes at different stages during the course of infection (candidiasis). For
      example, hyphae are considered to be the invasive form, which causes tissue
      damage, while yeast cells are predominant in the commensal stage. Here, we
      described interactions of C. albicans with its human host in a game theoretic
      model. In the game, players are fungal cells. Each fungal cell can adopt one of
      the two strategies: to exist as a yeast or hyphal cell. We characterized the
      ranges of model parameters in which the coexistence of both yeast and hyphal
      forms is plausible. Stability analysis of the system showed that, in theory, a
      reduced ability of the host to specifically recognize yeast and hyphal cells can
      result in bi-stability of the microbial populations' profile. Inspired by the
      model analysis we reasoned that the types of microbial interactions can change
      during invasive candidiasis. We found that positive cooperation among fungal
      cells occurs in mild infections and an enhanced tendency to invade the host is
      associated with negative cooperation. The model can easily be extended to multi
      player systems with direct application to identifying individuals that enhance
      either positive or negative cooperation. Results of the modeling approach have
      potential application in developing treatment strategies. 

PMID- 24567728
TI  - Fish oil diet associated with acute reperfusion related hemorrhage, and with
      reduced stroke-related sickness behaviors and motor impairment.
AB  - Ischemic stroke is associated with motor impairment and increased incidence of
      affective disorders such as anxiety/clinical depression. In non-stroke
      populations, successful management of such disorders and symptoms has been
      reported following diet supplementation with long chain omega-3-polyunsaturated
      fatty-acids (PUFAs). However, the potential protective effects of PUFA
      supplementation on affective behaviors after experimentally induced stroke and
      sham surgery have not been examined previously. This study investigated the
      behavioral effects of PUFA supplementation over a 6-week period following either
      middle cerebral artery occlusion or sham surgery in the hooded-Wistar rat. The
      PUFA diet supplied during the acclimation period prior to surgery was found to be
      associated with an increased risk of acute hemorrhage following the reperfusion
      component of the surgery. In surviving animals, PUFA supplementation did not
      influence infarct size as determined 6 weeks after surgery, but did decrease
      omega-6-fatty-acid levels, moderate sickness behaviors, acute motor impairment,
      and longer-term locomotor hyperactivity and depression/anxiety-like behavior. 

PMID- 24567729
TI  - Flavoprotein monooxygenases for oxidative biocatalysis: recombinant expression in
      microbial hosts and applications.
AB  - External flavoprotein monooxygenases comprise a group of flavin-dependent
      oxidoreductases that catalyze the insertion of one atom of molecular oxygen into
      an organic substrate and the second atom is reduced to water. These enzymes are
      involved in a great number of metabolic pathways both in prokaryotes and
      eukaryotes. Flavoprotein monooxygenases have attracted the attention of
      researchers for several decades and the advent of recombinant DNA technology
      caused a great progress in the field. These enzymes are subjected to detailed
      biochemical and structural characterization and some of them are also regarded as
      appealing oxidative biocatalysts for the production of fine chemicals and
      valuable intermediates toward active pharmaceutical ingredients due to their high
      chemo-, stereo-, and regioselectivity. Here, we review the most representative
      reactions catalyzed both in vivo and in vitro by prototype flavoprotein
      monooxygenases, highlighting the strategies employed to produce them
      recombinantly, to enhance the yield of soluble proteins, and to improve cofactor
      regeneration in order to obtain versatile biocatalysts. Although we describe the
      most outstanding features of flavoprotein monooxygenases, we mainly focus on
      enzymes that were cloned, expressed and used for biocatalysis during the last
      years. 

PMID- 24567731
TI  - Development of pVCR94DeltaX from Vibrio cholerae, a prototype for studying
      multidrug resistant IncA/C conjugative plasmids.
AB  - Antibiotic resistance has grown steadily in Vibrio cholerae over the last few
      decades to become a major threat in countries affected by cholera. Multi-drug
      resistance (MDR) spreads among clinical and environmental V. cholerae strains by
      lateral gene transfer often mediated by integrative and conjugative elements
      (ICEs) of the SXT/R391 family. However, in a few reported but seemingly isolated
      cases, MDR in V. cholerae was shown to be associated with other self
      transmissible genetic elements such as conjugative plasmids. IncA/C conjugative
      plasmids are often found associated with MDR in isolates of Enterobacteriaceae.
      To date, IncA/C plasmids have not been commonly found in V. cholerae or other
      species of Vibrio. Here we present a detailed analysis of pVCR94DeltaX derived
      from pVCR94, a novel IncA/C conjugative plasmid identified in a V. cholerae
      clinical strain isolated during the 1994 Rwandan cholera outbreak. pVCR94 was
      found to confer resistance to sulfamethoxazole, trimethoprim, ampicillin,
      streptomycin, tetracycline, and chloramphenicol and to transfer at very high
      frequency. Sequence analysis revealed its mosaic nature as well as high
      similarity of the core genes responsible for transfer and maintenance with other
      IncA/C plasmids and ICEs of the SXT/R391 family. Although IncA/C plasmids are
      considered a major threat in antibiotics resistance, their basic biology has
      received little attention, mostly because of the difficulty to genetically
      manipulate these MDR conferring elements. Therefore, we developed a convenient
      derivative from pVCR94, pVCR94Delta X, a 120.5-kb conjugative plasmid which only
      codes for sulfamethoxazole resistance. Using pVCR94Delta X, we identified the
      origin of transfer (oriT) and discovered an essential gene for transfer, both
      located within the shared backbone, allowing for an annotation update of all
      IncA/C plasmids. pVCR94Delta X may be a useful model that will provide new
      insights on the basic biology of IncA/C conjugative plasmids. 

PMID- 24567734
TI  - The nature of activatory and tolerogenic dendritic cell-derived signal 2.

PMID- 24567733
TI  - Three-Dimensional Human Skin Models to Understand Staphylococcus aureus Skin
      Colonization and Infection.
AB  - Staphylococcus aureus is both a major bacterial pathogen as well as a common
      member of the human skin microbiota. Due to its widespread prevalence as an
      asymptomatic skin colonizer and its importance as a source of skin and soft
      tissue infections, an improved understanding of how S. aureus attaches to, grows
      within, and breaches the stratified layers of the epidermis is of critical
      importance. Three-dimensional organotypic human skin culture models are
      informative and tractable experimental systems for future investigations of the
      interactions between S. aureus and the multi-faceted skin tissue. We propose that
      S. aureus virulence factors, primarily appreciated for their role in pathogenesis
      of invasive infections, play alternative roles in promoting asymptomatic
      bacterial growth within the skin. Experimental manipulations of these cultures
      will provide insight into the many poorly understood molecular interactions
      occurring at the interface between S. aureus and stratified human skin tissue. 

PMID- 24567732
TI  - Complexity of Interferon-gamma Interactions with HSV-1.
AB  - The intricacies involving the role of interferon-gamma (IFN-gamma) in herpesvirus
      infection and persistence are complex. Herpes simplex virus type 1 (HSV-1) uses a
      variety of receptors to enter cells and is transported to and from the host cell
      nucleus over the microtubule railroad via retrograde and anterograde transport.
      IFN-gamma exerts dual but conflicting effects on microtubule organization. IFN
      gamma stimulates production of suppressors of cytokine signaling 1 and 3 (SOCS1
      and SOCS3), which are involved in microtubule stability and are negative
      regulators of IFN-gamma signaling when overexpressed. IFN-gamma also interferes
      with the correct assembly of microtubules causing them to undergo severe
      bundling, contributing to its anti-viral effect. Factors leading to the decision
      for a replicative virus lytic cycle or latency in the trigeminal ganglion (TG)
      occur on histone 3 (H3), involve IFN-gamma produced by natural killer cells and
      non-cytolytic CD8(+)T cells, SOCS1, SOCS3, and M2 anti-inflammatory
      microglia/macrophages maintained by inhibitory interleukin 10 (IL-10). Both M2
      microglia and CD4(+)CD25(+)Foxp3(+) Treg cells produce IL-10. Histone
      deacetylases (HDACs) are epigenetic regulators maintaining chromatin in an
      inactive state necessary for transcription of IFN-gamma-activated genes and their
      anti-viral effect. Following inhibition of HDACs by stressors such as ultraviolet
      light, SOCS1 and SOCS3 are acetylated, and chromatin is relaxed and available for
      virus replication. SOCS1 prevents expression of MHC class 1 molecules on neuronal
      cells and SOCS3 attenuates cytokine-induced inflammation in the area. A model is
      presented to unify the effects of IFN-gamma, SOCS1, SOCS3, and HSV-1 on H3 and
      chromatin structure in virus latency or reactivation. HSV-1 latency in the TG is
      viewed as an active ongoing process involving maintenance of microglia in an M2
      anti-inflammatory state by IL-10. IL-10 is produced in an autocrine manner by the
      M2 microglia/macrophages and by virus-specific CD4(+)Foxp3(+) Treg cells
      interacting with virus-specific non-cytolytic CD8(+) T cells. 

PMID- 24567735
TI  - Associations between the acclimation of phloem-cell wall ingrowths in minor veins
      and maximal photosynthesis rate.
AB  - The companion cells (CCs) and/or phloem parenchyma cells (PCs) in foliar minor
      veins of some species exhibit invaginations that are amplified when plants
      develop in high light (HL) compared to low light (LL). Leaves of plants that
      develop under HL also exhibit greater maximal rates of photosynthesis compared to
      those that develop under LL, suggesting that the increased membrane area of CCs
      and PCs of HL-acclimated leaves may provide for greater levels of transport
      proteins facilitating enhanced sugar export. Furthermore, the degree of wall
      invagination in PCs (Arabidopsis thaliana) or CCs (pea) of fully expanded LL
      acclimated leaves increased to the same level as that present in HL-acclimated
      leaves 7 days following transfer to HL, and maximal photosynthesis rates of
      transferred leaves of both species likewise increased to the same level as in HL
      acclimated leaves. In contrast, transfer of Senecio vulgaris from LL to HL
      resulted in increased wall invagination in CCs, but not PCs, and such leaves
      furthermore exhibited only partial upregulation of photosynthetic capacity
      following LL to HL transfer. Moreover, a significant linear relationship existed
      between the level of cell wall ingrowths and maximal photosynthesis rates across
      all three species and growth light regimes. A positive linear relationship
      between these two parameters was also present for two ecotypes (Sweden, Italy) of
      the winter annual A. thaliana in response to growth at different temperatures,
      with significantly greater levels of PC wall ingrowths and higher rates of
      photosynthesis in leaves that developed at cooler versus warmer temperatures.
      Treatment of LL-acclimated plants with the stress hormone methyl jasmonate also
      resulted in increased levels of wall ingrowths in PCs of A. thaliana and S.
      vulgaris but not in CCs of pea and S. vulgaris. The possible role of PC wall
      ingrowths in sugar export versus as physical barriers to the movement of
      pathogens warrants further attention. 

PMID- 24567736
TI  - Cytoplasmic 5'-3' exonuclease Xrn1p is also a genome-wide transcription factor in
      yeast.
AB  - The 5' to 3' exoribonuclease Xrn1 is a large protein involved in cytoplasmatic
      mRNA degradation as a critical component of the major decaysome. Its deletion in
      the yeast Saccharomyces cerevisiae is not lethal, but it has multiple
      physiological effects. In a previous study, our group showed that deletion of all
      tested components of the yeast major decaysome, including XRN1, results in a
      decrease in the synthetic rate and an increase in half-life of most mRNAs in a
      compensatory manner. Furthermore, the same study showed that the all tested
      decaysome components are also nuclear proteins that bind to the 5' region of a
      number of genes. In the present work, we show that disruption of Xrn1 activity
      preferentially affects both the synthesis and decay of a distinct subpopulation
      of mRNAs. The most affected mRNAs are the transcripts of the highly transcribed
      genes, mainly those encoding ribosome biogenesis and translation factors.
      Previously, we proposed that synthegradases play a key role in regulating both
      mRNA synthesis and degradation. Evidently, Xrn1 functions as a synthegradase,
      whose selectivity might help coordinating the expression of the protein synthetic
      machinery. We propose to name the most affected genes "Xrn1 synthegradon." 

PMID- 24567737
TI  - On the optimal trimming of high-throughput mRNA sequence data.
AB  - The widespread and rapid adoption of high-throughput sequencing technologies has
      afforded researchers the opportunity to gain a deep understanding of genome level
      processes that underlie evolutionary change, and perhaps more importantly, the
      links between genotype and phenotype. In particular, researchers interested in
      functional biology and adaptation have used these technologies to sequence mRNA
      transcriptomes of specific tissues, which in turn are often compared to other
      tissues, or other individuals with different phenotypes. While these techniques
      are extremely powerful, careful attention to data quality is required. In
      particular, because high-throughput sequencing is more error-prone than
      traditional Sanger sequencing, quality trimming of sequence reads should be an
      important step in all data processing pipelines. While several software packages
      for quality trimming exist, no general guidelines for the specifics of trimming
      have been developed. Here, using empirically derived sequence data, I provide
      general recommendations regarding the optimal strength of trimming, specifically
      in mRNA-Seq studies. Although very aggressive quality trimming is common, this
      study suggests that a more gentle trimming, specifically of those nucleotides
      whose Phred score <2 or <5, is optimal for most studies across a wide variety of
      metrics. 

PMID- 24567739
TI  - Customising PRESAGE(r) for diverse applications.
AB  - PRESAGE(r) is a solid radiochromic dosimeter consisting of a polyurethane matrix,
      a triarylmethane leuco dye, and a trihalomethane initiator. Varying the
      composition and/or relative amounts of these constituents can affect the dose
      sensitivity, post-irradiation stability, and physical properties of the
      dosimeter. This allows customisation of PRESAGE(r) to meet application-specific
      requirements, such as low sensitivity for high dose applications, stability for
      remote dosimetry, optical clearing for reusability, and tissue-like elasticity
      for deformable dosimetry. This study evaluates five hard, non-deformable
      PRESAGE(r) formulations and six deformable PRESAGE(r) formulations and
      characterizes them for dose sensitivity and stability. Results demonstrated
      sensitivities in the range of 0.0029 - 0.0467 DeltaOD/(Gy.cm) for hard
      formulations and 0.0003 - 0.0056 DeltaOD/(Gy.cm) for deformable formulations.
      Exceptional stability was seen in both standard and low sensitivity non
      deformable formulations, with promising applications for remote dosimetry.
      Deformable formulations exhibited potential for reusability with strong post
      irradiation optical clearing. Tensile compression testing of the deformable
      formulations showed elastic response consistent with soft tissues, with further
      testing required for direct comparison. These results demonstrate that PRESAGE(r)
      dosimeters have the flexibility to be adapted for a wide spectrum of clinical
      applications.

PMID- 24567738
TI  - Assessing the quality of studies supporting genetic susceptibility and outcomes
      of ARDS.
AB  - The acute respiratory distress syndrome (ARDS) is a severe inflammatory disease
      manifested as a result of pulmonary and systemic responses to several insults. It
      is now well accepted that genetic variation influences these responses. However,
      little is known about the genes that are responsible for patient susceptibility
      and outcome of ARDS. Methodological flaws are still abundant among genetic
      association studies with ARDS and here, we aimed to highlight the quality
      criteria where the standards have not been reached, to expose the associated
      genes to facilitate replication attempts, and to provide quick-reference guidance
      for future studies. We conducted a PubMed search from January 2008 to September
      2012 for original articles. Studies were considered if a statistically
      significant association was declared with either susceptibility or outcomes of
      all-cause ARDS. Fourteen criteria were used for evaluation and results were
      compared to those from a previous quality assessment report. Significant
      improvements affecting study design and statistical analysis were detected.
      However, major issues such as adjustments for the underlying population
      stratification and replication studies remain poorly addressed. 

PMID- 24567740
TI  - Comprehensive quality assurance for base of skull IMRT.
AB  - Six base of skull IMRT treatment plans were delivered to Presage dosimeters
      within the RPC Head and Neck Phantom for quality assurance (QA) verification.
      Isotropic 2mm 3D data were acquired by optical-CT scanning with the DLOS system
      (Duke Large Optical-CT Scanner) and compared to the Eclipse (Varian) treatment
      plan. Normalized Dose Distribution (NDD) pass rates were obtained for a number of
      criteria. High quality 3D dosimetry data was observed from the DLOS system,
      illustrated here through colormaps, isodose lines, and profiles. Excellent
      agreement with the planned dose distributions was also observed with NDD analysis
      revealing > 90% pass rates (with criteria 3%, 2mm), and noise < 0.5%. The results
      comprehensively confirm the high accuracy of base-of-skull IMRT treatment in our
      clinic.

PMID- 24567742
TI  - History of the invasive African olive tree in Australia and Hawaii: evidence for
      sequential bottlenecks and hybridization with the Mediterranean olive.
AB  - Humans have introduced plants and animals into new continents and islands with
      negative effects on local species. This has been the case of the olive that was
      introduced in Australia, New Zealand and Pacific islands where it became
      invasive. Two subspecies were introduced in Australia, and each successfully
      invaded a specific area: the African olive in New South Wales (NSW) and the
      Mediterranean olive in South Australia. Here, we examine their origins and spread
      and analyse a large sample of native and invasive accessions with chloroplast and
      nuclear microsatellites. African olive populations from the invaded range exhibit
      two South African chlorotypes hence supporting an introduction from South Africa,
      while populations from South Australia exhibit chlorotypes of Mediterranean
      cultivars. Congruently, nuclear markers support the occurrence of two lineages in
      Australia but demonstrate that admixture took place, attesting that they
      hybridized early after introduction. Furthermore, using an approximate Bayesian
      computation framework, we found strong support for the serial introduction of the
      African olive from South Africa to NSW and then from NSW to Hawaii. The taxon
      experienced successive bottlenecks that did not preclude invasion, meaning that
      rapid decisions need to be taken to avoid naturalization where it has not
      established a large population yet. 

PMID- 24567743
TI  - Combining genetic and demographic information to prioritize conservation efforts
      for anadromous alewife and blueback herring.
AB  - A major challenge in conservation biology is the need to broadly prioritize
      conservation efforts when demographic data are limited. One method to address
      this challenge is to use population genetic data to define groups of populations
      linked by migration and then use demographic information from monitored
      populations to draw inferences about the status of unmonitored populations within
      those groups. We applied this method to anadromous alewife (Alosa pseudoharengus)
      and blueback herring (Alosa aestivalis), species for which long-term demographic
      data are limited. Recent decades have seen dramatic declines in these species,
      which are an important ecological component of coastal ecosystems and once
      represented an important fishery resource. Results show that most populations
      comprise genetically distinguishable units, which are nested geographically
      within genetically distinct clusters or stocks. We identified three distinct
      stocks in alewife and four stocks in blueback herring. Analysis of available time
      series data for spawning adult abundance and body size indicate declines across
      the US ranges of both species, with the most severe declines having occurred for
      populations belonging to the Southern New England and the Mid-Atlantic Stocks.
      While all alewife and blueback herring populations deserve conservation
      attention, those belonging to these genetic stocks warrant the highest
      conservation prioritization. 

PMID- 24567744
TI  - Genomic selection for recovery of original genetic background from hybrids of
      endangered and common breeds.
AB  - Critically endangered breeds and populations are often crossed with more common
      breeds or subspecies. This results in genetic admixture that can be undesirable
      when it challenges the genetic integrity of wild and domestic populations,
      causing a loss in special characteristics or unique genetic material and
      ultimately extinction. Here, we present two genomic selection strategies, using
      genome-wide DNA markers, to recover the genomic content of the original
      endangered population from admixtures. Each strategy relies on the estimation of
      the proportion of nonintrogressed genome in individuals based on a different
      method: either genomic prediction or identification of breed-specific haplotypes.
      Then, breeding programs that remove introgressed genomic information can be
      designed. To test these strategies, we used empirical 50K SNP array data from two
      pure sheep breeds, Merino (used as target breed), Poll Dorset and an existing
      admixed population of both breeds. Sheep populations with varying degrees of
      introgression and admixture were simulated starting from these real genotypes.
      Both strategies were capable of identifying segment origin, and both removed up
      to the 100% of the Poll Dorset segments. While the selection process led to
      substantial inbreeding, we controlled it by imposing a minimum number of
      individuals contributing to the next generation. 

PMID- 24567745
TI  - Evaluation of rockfish conservation area networks in the United States and Canada
      relative to the dispersal distance for black rockfish (Sebastes melanops).
AB  - Marine reserves networks are implemented as a way to mitigate the impact of
      fishing on marine ecosystems. Theory suggests that a reserve network will
      function synergistically when connected by dispersal, but the scale of dispersal
      is often unknown. On the Pacific coast of the United States and Canada, both
      countries have recently implemented a number of rockfish conservation areas
      (RCAs) to protect exploited rockfish species, but no study has evaluated the
      connectivity within networks in each country or between the two countries. We
      used isolation-by-distance theory to estimate the scale of dispersal from
      microsatellite data in the black rockfish, Sebastes melanops, and compared this
      estimate with the distance between RCAs that would protect this species. Within
      each country, we found that the distance between RCAs was generally within the
      confidence intervals of mean dispersal per generation. The distance between these
      two RCA networks, however, was greater than the average dispersal per generation.
      The data were also consistent with a genetic break between southern Oregon and
      central Oregon. We discuss whether additional nearshore RCAs in southern Oregon
      and Washington would help promote connectivity between RCA's for shallow-water
      rockfishes. 

PMID- 24567746
TI  - Anthropogenic selection enhances cancer evolution in Tasmanian devil tumours.
AB  - The Tasmanian Devil Facial Tumour Disease (DFTD) provides a unique opportunity to
      elucidate the long-term effects of natural and anthropogenic selection on cancer
      evolution. Since first observed in 1996, this transmissible cancer has caused
      local population declines by >90%. So far, four chromosomal DFTD variants
      (strains) have been described and karyotypic analyses of 253 tumours showed
      higher levels of tetraploidy in the oldest strain. We propose that increased
      ploidy in the oldest strain may have evolved in response to effects of genomic
      decay observed in asexually reproducing organisms. In this study, we focus on the
      evolutionary response of DFTD to a disease suppression trial. Tumours collected
      from devils subjected to the removal programme showed accelerated temporal
      evolution of tetraploidy compared with tumours from other populations where no
      increase in tetraploid tumours were observed. As ploidy significantly reduces
      tumour growth rate, we suggest that the disease suppression trial resulted in
      selection favouring slower growing tumours mediated by an increased level of
      tetraploidy. Our study reveals that DFTD has the capacity to rapidly respond to
      novel selective regimes and that disease eradication may result in novel tumour
      adaptations, which may further imperil the long-term survival of the world's
      largest carnivorous marsupial. 

PMID- 24567747
TI  - Genetic assessment of a summer chum salmon metapopulation in recovery.
AB  - Programs to rebuild imperiled wild fish populations often include hatchery-born
      fish derived from wild populations to supplement natural spawner abundance. These
      programs require monitoring to determine their demographic, biological, and
      genetic effects. In 1990s in Washington State, the Summer Chum Salmon
      Conservation Initiative developed a recovery program for the threatened Hood
      Canal summer chum salmon Evolutionarily Significant Unit (ESU) (the
      metapopulation) that used in-river spawners (wild fish) for each respective
      supplementation broodstock in six tributaries. Returning spawners (wild-born and
      hatchery-born) composed subsequent broodstocks, and tributary-specific
      supplementation was limited to three generations. We assessed impacts of the
      programs on neutral genetic diversity in this metapopulation using 16
      microsatellite loci and a thirty-year dataset spanning before and after
      supplementation, roughly eight generations. Following supplementation,
      differentiation among subpopulations decreased (but not significantly) and
      isolation by distance patterns remained unchanged. There was no decline in
      genetic diversity in wild-born fish, but hatchery-born fish sampled in the same
      spawning areas had significantly lower genetic diversity and unequal family
      representation. Despite potential for negative effects from supplementation
      programs, few were detected in wild-born fish. We hypothesize that chum salmon
      natural history makes them less vulnerable to negative impacts from hatchery
      supplementation. 

PMID- 24567748
TI  - Transcriptomic responses to high water temperature in two species of Pacific
      salmon.
AB  - Characterizing the cellular stress response (CSR) of species at ecologically
      relevant temperatures is useful for determining whether populations and species
      can successfully respond to current climatic extremes and future warming. In this
      study, populations of wild-caught adult pink (Oncorhynchus gorbuscha) and sockeye
      (Oncorhynchus nerka) salmon from the Fraser River, British Columbia, Canada, were
      experimentally treated to ecologically relevant 'cool' or 'warm' water
      temperatures to uncover common transcriptomic responses to elevated water
      temperature in non-lethally sampled gill tissue. We detected the differential
      expression of 49 microarray features (29 unique annotated genes and one gene with
      unknown function) associated with protein folding, protein synthesis, metabolism,
      oxidative stress and ion transport that were common between populations and
      species of Pacific salmon held at 19 degrees C compared with fish held at a
      cooler temperature (13 or 14 degrees C). There was higher mortality in fish held
      at 19 degrees C, which suggests a possible relationship between a temperature
      induced CSR and mortality in these species. Our results suggest that frequently
      encountered water temperatures >=19 degrees C, which are capable of inducing a
      common CSR across species and populations, may increase risk of upstream spawning
      migration failure for pink and sockeye salmon. 

PMID- 24567749
TI  - Linking genotype, ecotype, and phenotype in an intensively managed large
      carnivore.
AB  - Numerous factors influence fitness of free-ranging animals, yet often these are
      uncharacterized. We integrated GPS habitat use data and genetic profiling to
      determine their influence on fitness proxies (mass, length, and body condition)
      in a threatened population of grizzly bears (Ursus arctos) in Alberta, Canada. We
      detected distinct genetic and habitat use (ecotype) clusters, with individual
      cluster assignments, or genotype/ecotype, being correlated (Pearson r = 0.34, P <
      0.01). Related individuals showed evidence of similar habitat use patterns,
      irrespective of geographic distance and sex. Fitness proxies were influenced by
      sex, age, and habitat use, and homozygosity had a positive effect on these
      proxies that could be indicative of outbreeding depression. We further documented
      over 300 translocations occurring in the province since the 1970s, often to areas
      with significantly different habitat. We argue this could be unintentionally
      causing the pattern of outbreeding, although the heterozygosity correlation may
      instead be explained by the energetic costs associated with larger body size. The
      observed patterns, together with the unprecedented human-mediated migrations,
      make understanding the link between genotype, ecotype, and phenotype and
      mechanisms behind the negative heterozygosity-fitness correlations critical for
      management and conservation of this species. 

PMID- 24567750
TI  - Evolution of age and length at maturation of Alaskan salmon under size-selective
      harvest.
AB  - Spatial and temporal trends and variation in life-history traits, including age
      and length at maturation, can be influenced by environmental and anthropogenic
      processes, including size-selective exploitation. Spawning adults in many wild
      Alaskan sockeye salmon populations have become shorter at a given age over the
      past half-century, but their age composition has not changed. These fish have
      been exploited by a gillnet fishery since the late 1800s that has tended to
      remove the larger fish. Using a rare, long-term dataset, we estimated
      probabilistic maturation reaction norms (PMRNs) for males and females in nine
      populations in two basins and correlated these changes with fishery size
      selection and intensity to determine whether such selection contributed to
      microevolutionary changes in maturation length. PMRN midpoints decreased in six
      of nine populations for both sexes, consistent with the harvest. These results
      support the hypothesis that environmental changes in the ocean (likely from
      competition) combined with adaptive microevolution (decreased PMRNs) have
      produced the observed life-history patterns. PMRNs did not decrease in all
      populations, and we documented differences in magnitude and consistency of size
      selection and exploitation rates among populations. Incorporating evolutionary
      considerations and tracking further changes in life-history traits can support
      continued sustainable exploitation and productivity in these and other exploited
      natural resources. 

PMID- 24567751
TI  - No effect of seed source on multiple aspects of ecosystem functioning during
      ecological restoration: cultivars compared to local ecotypes of dominant grasses.
AB  - Genetic principles underlie recommendations to use local seed, but a paucity of
      information exists on the genetic distinction and ecological consequences of
      using different seed sources in restorations. We established a field experiment
      to test whether cultivars and local ecotypes of dominant prairie grasses were
      genetically distinct and differentially influenced ecosystem functioning. Whole
      plots were assigned to cultivar and local ecotype grass sources. Three subplots
      within each whole plot were seeded to unique pools of subordinate species. The
      cultivar of the increasingly dominant grass, Sorghastrum nutans, was genetically
      different than the local ecotype, but genetic diversity was similar between the
      two sources. There were no differences in aboveground net primary production,
      soil carbon accrual, and net nitrogen mineralization rate in soil between the
      grass sources. Comparable productivity of the grass sources among the species
      pools for four years shows functional equivalence in terms of biomass production.
      Subordinate species comprised over half the aboveground productivity, which may
      have diluted the potential for documented trait differences between the grass
      sources to influence ecosystem processes. Regionally developed cultivars may be a
      suitable alternative to local ecotypes for restoration in fragmented landscapes
      with limited gene flow between natural and restored prairie and negligible
      recruitment by seed. 

PMID- 24567753
TI  - Serum cytokeratin 19 fragment in advanced lung cancer: could we eventually have a
      serum tumor marker?
AB  - INTRODUCTION: Lung cancer is one of the most lethal malignancies; however, no
      serum marker has been routinely recommended until now. METHODS: THIS IS A
      PROSPECTIVE CASE CONTROL STUDY INCLUDING TWO GROUPS OF PATIENTS: Group I-patients
      with advanced lung cancer and Group II-patients with benign lung disease as
      control. Serum cytokeratin 19 (CK19) fragment levels were measured at baseline by
      real-time polymerase chain reaction before first-line chemotherapy. The CK19 cut
      off taken was 15-cycle threshold. The primary end point was the comparison of
      high CK19 in cases and controls. The secondary end point was the correlation
      between high CK19 and progressive disease (PD), progression-free survival, and
      overall survival (OS) in advanced lung cancer patients. RESULTS: A total of 30
      patients with advanced lung cancer (16 non-small and 14 small cell lung cancer)
      and 15 patients with benign lung disease were included and followed up during the
      period from October 2008 to October 2011 with median follow-up of one and half
      years. High CK19 was found in 90% of lung cancer cases as compared with 7% in
      controls (p < 0.001). High CK19 was found in all cases showing PD (p = 0.04). One
      year OS in high CK was 61% as compared with 33% in normal CK (p = 0.1).
      CONCLUSION: Serum CK19 fragment is a potential diagnostic and prognostic marker
      for advanced lung cancer.

PMID- 24567754
TI  - Leukaemic pleural effusion as a manifestation of acute myeloid leukaemia: a case
      report and review of literature.
AB  - Haematologic malignancies such as acute and chronic leukaemias rarely present
      with or develop pleural effusion during their clinical course. We present a case
      of a young female who presented with unilateral pleural effusion and was
      diagnosed with haematologic malignancy on pleural fluid cytology. On further
      workup, a diagnosis of acute myeloid leukaemia was established. The patient was
      put on chemotherapy thereafter. This case clearly highlights the importance of
      cytopathology aids in making a diagnosis of rare and unusual presentation in
      haematologic malignancies. 

PMID- 24567755
TI  - The p-medicine portal-a collaboration platform for research in personalised
      medicine.
AB  - The European project p-medicine creates an information technology infrastructure
      that facilitates the development from current medical practice to personalised
      medicine. The main access point to this infrastructure is the p-medicine portal
      that provides clinicians, patients, and researchers a platform to collaborate,
      share data and expertise, and use tools and services to improve personalised
      treatments of patients. In this document, we describe the community-based
      structure of the p-medicine portal and provide information about the p-medicine
      security framework implemented in the portal. Finally, we show the user interface
      and describe the p-medicine tools and services integrated in the portal. 

PMID- 24567756
TI  - Usability on the p-medicine infrastructure: an extended usability concept.
AB  - Usability testing methods are nowadays integrated into the design and development
      of health-care software, and the need for usability in health-care information
      technology (IT) is widely accepted by clinicians and researchers. Usability
      assessment starts with the identification of specific objectives that need to be
      tested and continues with the definition of evaluation criteria and monitoring
      procedures before usability tests are performed to assess the quality of all
      services and tasks. Such a process is implemented in the p-medicine environment
      and gives feedback iteratively to all software developers in the project. GCP
      (good clinical practice) criteria require additional usability testing of the
      software. For the p-medicine project (www.p-medicine.eu), an extended usability
      concept (EUC) was developed. The EUC covers topics like ease of use, likeability,
      and usefulness, usability in trial centres characterised by a mixed care and
      research environment and by extreme time constraints, confidentiality, use of
      source documents, standard operating procedures (SOA), and quality control during
      data handling to ensure that all data are reliable and have been processed
      correctly in terms of accuracy, completeness, legibility, consistence, and
      timeliness. Here, we describe the p-medicine EUC, focusing on two of the many key
      tools: ObTiMA and the Ontology Annotator (OA). 

PMID- 24567757
TI  - Development of interactive empowerment services in support of personalised
      medicine.
AB  - In an epoch where shared decision making is gaining importance, a patient's
      commitment to and knowledge about his/her health condition is becoming more and
      more relevant. Health literacy is one of the most important factors in enhancing
      the involvement of patients in their care. Nevertheless, other factors can impair
      patient processing and understanding of health information: psychological aspects
      and cognitive style may affect the way patients approach, select, and retain
      information. This paper describes the development and validation of a short and
      easy to fill-out questionnaire that measures and collects psycho-cognitive
      information about patients, named ALGA-C. ALGA-C is a multilingual, multidevice
      instrument, and its validation was carried out in healthy people and breast
      cancer patients. In addition to the aforementioned questionnaire, a patient
      profiling mechanism has also been developed. The ALGA-C Profiler enables
      physicians to rapidly inspect each patient's individual cognitive profile and see
      at a glance the areas of concern. With this tool, doctors can modulate the
      language, vocabulary, and content of subsequent discussions with the patient,
      thus enabling easier understanding by the patient. This, in turn, helps the
      patient formulate questions and participate on an equal footing in the decision
      making processes. Finally, a preview is given on the techniques under
      consideration for exploiting the constructed patient profile by a personal health
      record (PHR). Predefined rules will use a patient's profile to personalise the
      contents of the information presented and to customise ways in which users
      complete their tasks in a PHR system. This optimises information delivery to
      patients and makes it easier for the patient to decide what is of interest to
      him/her at the moment. 

PMID- 24567758
TI  - p-BioSPRE-an information and communication technology framework for transnational
      biomaterial sharing and access.
AB  - Biobanks represent key resources for clinico-genomic research and are needed to
      pave the way to personalised medicine. To achieve this goal, it is crucial that
      scientists can securely access and share high-quality biomaterial and related
      data. Therefore, there is a growing interest in integrating biobanks into larger
      biomedical information and communication technology (ICT) infrastructures. The
      European project p-medicine is currently building an innovative ICT
      infrastructure to meet this need. This platform provides tools and services for
      conducting research and clinical trials in personalised medicine. In this paper,
      we describe one of its main components, the biobank access framework p-BioSPRE (p
      medicine Biospecimen Search and Project Request Engine). This generic framework
      enables and simplifies access to existing biobanks, but also to offer own
      biomaterial collections to research communities, and to manage biobank specimens
      and related clinical data over the ObTiMA Trial Biomaterial Manager. p-BioSPRE
      takes into consideration all relevant ethical and legal standards, e.g.,
      safeguarding donors' personal rights and enabling biobanks to keep control over
      the donated material and related data. The framework thus enables secure sharing
      of biomaterial within open and closed research communities, while flexibly
      integrating related clinical and omics data. Although the development of the
      framework is mainly driven by user scenarios from the cancer domain, in this
      case, acute lymphoblastic leukaemia and Wilms tumour, it can be extended to
      further disease entities. 

PMID- 24567759
TI  - Repeatable antibiotic prescriptions: an assessment of patient attitudes,
      knowledge and advice from health professionals.
AB  - BACKGROUND: Previous Australian research has identified that general practice
      software systems appear to be associated with an increase in repeatable
      antibiotic prescriptions. Such prescriptions potentially facilitate the use of
      antibiotics without medical consultation and may be inconsistent with attempts to
      promote prudent use of antimicrobials. AIMS: We sought to assess knowledge and
      attitudes to antibiotics amongst patients presenting with a repeatable
      prescription; and the provision of supporting advice from healthcare
      professionals regarding use of these repeats. METHOD: Six community pharmacies
      across Tasmania invited patients presenting with a repeatable antibiotic
      prescription to participate in the study. Participants were asked to complete a
      questionnaire and return this to the research team in a pre-paid envelope.
      RESULTS: Fifty-seven of 244 (23 per cent) surveys were returned. Regarding
      provision of advice on use of the repeat, 14 (25 per cent) of respondents stated
      that they were given no advice by the prescriber and 19 (30 per cent) no advice
      from the pharmacist. Five (9 per cent) were given no advice from either
      prescriber or pharmacist. One-third of respondents indicated that they would keep
      the repeat for future use and around three-quarters perceived no major safety
      concerns with antibiotics. CONCLUSION: Further research is needed, however, this
      small study suggests that provision of information to patients regarding
      appropriate use of repeatable antibiotic prescriptions is suboptimal. This
      coupled with existing patient knowledge and attitudes may contribute to
      inappropriate use of antibiotics.

PMID- 24567760
TI  - An uncommon cause of ascites: spontaneous rupture of biliary cystadenoma.
AB  - Biliary cystadenomas are cystic hepatic tumours of biliary origin. Cystadenomas
      are often slow-growing benign tumours, but always harbour the risk of malignant
      transformation. Cystadenomas are often asymptomatic, but may present with
      abdominal pain and distension. Though suspected with cross-sectional abdominal
      imaging, definitive diagnosis almost always requires histology. Spontaneous
      rupture of cystadenoma had been reported three times in the medical literature to
      date, all presenting with peritonitis. Here we report a case of spontaneous
      intraperitoneal rupture of biliary cystadenoma presenting as ascites without
      peritonitis. 

PMID- 24567761
TI  - Hepatitis C, a silent threat to the community of Haryana, India: a community
      based study.
AB  - BACKGROUND: Hepatitis C is a global public health problem. As many as 12 million
      people may be chronically infected in India and most are unaware of it. AIMS: To
      determine the incidence of hepatitis C in the Ratia block of the Fatehabad
      district, Haryana, India. METHOD: This cross-sectional study was carried out by
      house-tohouse visits over 2 weeks. After obtaining written consent, a blood
      sample was drawn from suspected cases by a laboratory technician maintaining all
      necessary safety precautions and sterilization. RESULTS: Of the samples, 1,630
      (22.3 per cent) were found to be positive for hepatitis C by ELISA, 253 (15.5 per
      cent) patients were previously hepatitis C positive, and adults (21-60 years)
      were affected maximally (70.0 per cent). CONCLUSION: The study emphasises the
      need for public awareness campaigns at various levels and prevention of HCV
      infection. It also suggests the need to develop and strengthen evaluation
      methodology for the Integrated Disease Surveillance Project (IDSP).

PMID- 24567762
TI  - Pharmacy practice and its challenges in Yemen.
AB  - BACKGROUND: Pharmacy practice in Yemen was established in 1875 in Aden.
      OBJECTIVES: To describe pharmacy practice as it currently exists in Yemen, the
      challenges the profession faces, and to recommend changes that will improve
      pharmaceutical care services. METHODS: This study has two parts. Part 1 comprised
      a literature search performed between May and July 2011 to identify published
      studies on pharmacy practice in Yemen. Full text papers, abstracts, and reports
      in Arabic or English between 1970 and 2011 were reviewed. Part 2 consisted of a
      qualitative study with face-to-face interviews with a representative sample of
      pharmacists, staff from the Ministry of Public Health and Population (MoPHP), and
      patients. RESULTS: The analysis revealed several issues that plague pharmacy
      practice in Yemen: Fewer than 10 per cent of pharmacists working in pharmacies
      and drug stores are graduates of governmentrecognised colleges.Most Yemeni
      pharmacists are dissatisfied with their work conditions and
      opportunities.Medicines are expensive and hard to access in Yemen, and
      counterfeit medicines are a serious problem.Few regulations and standards exist
      for pharmacists and pharmaceutical care.Pharmaceutical marketing plays an
      important role in marketing and selling products in Yemen.A dearth of standards,
      regulations, and laws are hurting pharmacy practice in the country and
      potentially endangering peoples' lives. CONCLUSION: In order to improve pharmacy
      practice in Yemen, many changes are needed, including updating the pharmacy
      curriculum taught, implementing industry standards for pharmacy practice,
      implementing and reinforcing laws, and integrating pharmacists more fully in the
      healthcare industry. Additionally, the quality of the pharmacy workforce needs to
      be improved, and there needs to be increased awareness by the public, physicians,
      other healthcare professionals, and policy makers about the value of pharmacists.

PMID- 24567763
TI  - Quality of patient health information on the Internet: reviewing a complex and
      evolving landscape.
AB  - BACKGROUND: The popularity of the Internet has enabled unprecedented access to
      health information. As a largely unregulated source, there is potential for
      inconsistency in the quality of information that reaches the patient. AIMS: To
      review the literature relating to the quality indicators of health information
      for patients on the Internet. METHOD: A search of English language literature was
      conducted using PubMed, Google Scholar and EMBASE databases. RESULTS: Many
      articles have been published which assess the quality of information relating to
      specific medical conditions. Indicators of quality have been defined in an
      attempt to predict higher quality health information on the Internet. Quality
      evaluation tools are scoring systems based on indicators of quality. Established
      tools such as the HONcode may help patients navigate to more reliable
      information. Google and Wikipedia are important emerging sources of patient
      health information. CONCLUSION: The Internet is crucial for modern dissemination
      of health information, but it is clear that quality varies significantly between
      sources. Quality indicators for web-information have been developed but there is
      no agreed standard yet. We envisage that reliable rating tools, effective search
      engine ranking and progress in crowd-edited websites will enhance patient access
      to health information on the Internet.

PMID- 24567764
TI  - Clinical profile of urinary tract infections in diabetics and non-diabetics.
AB  - BACKGROUND: The risk of urinary tract infection (UTI) is higher in diabetics
      compared to non-diabetics. The aetiology and the antibiotic resistance of
      uropathogens have been changing over the past years. Hence the study was
      undertaken to determine if there are differences in clinical and microbiological
      features of UTI between diabetic and non-diabetic subjects, to study the
      influence of diabetes mellitus on the uropathogens and antibiotic sensitivity
      pattern in patients with UTI. METHOD: A total of 181 diabetics (83 males and 98
      females) and 124 non-diabetic subjects (52 males and 72 females) with culture
      positive UTI were studied. Patients with negative urine culture (n= 64), those
      diagnosed and treated outside (n= 83) and not willing to participate in the study
      (n= 24) were excluded. RESULTS: Almost 30 per cent of the patients (both
      diabetics and nondiabetics) presented with asymptomatic bacteriuria and the
      prevalence of pyelonephritis was significantly higher (p= 0.04) in diabetics
      compared to non-diabetic patients. The majority of the diabetics with UTI (87.14
      per cent) had glycosylated haemoglobin (HbA1c) > 6.5 per cent with p < 0.001. The
      isolation rate of Escherichia coli (E. coli) from urine culture was higher (64.6
      per cent) among diabetic patients followed by Klebsiella (12.1 per cent) and
      Enterococcus (9.9 per cent). The prevalence of extendedspectrum beta-lactamase
      (ESBL) producing E.coli was significantly higher in diabetics (p= 0.001) compared
      to nondiabetics. E.coli showed maximum sensitivity to carbapenems in both
      diabetic and non-diabetic subjects and least susceptibility to ampicillin.
      CONCLUSION: The prevalence of pyelonephritis is significantly higher in diabetics
      than in non-diabetic subjects, with E. coli being the most common isolate.
      Elevated glycosylated hemoglobin (HbA1c) predisposes diabetics to UTI.
      Investigation of bacteriuria in diabetic patients for urinary tract infection is
      important for treatment and prevention of renal complications.

PMID- 24567765
TI  - Assessment of general public satisfaction with public healthcare services in
      Kedah, Malaysia.
AB  - BACKGROUND: Patient satisfaction is considered an essential component of
      healthcare services evaluation and an additional indicator of the quality of
      healthcare. Moreover, patient satisfaction may also predict health-related
      behaviours of patients such as adherence to treatment and recommendations. AIMS:
      The study aimed to assess patients' level of satisfaction with public healthcare
      services and to explore the association between socio-demographic and other study
      variables and patient satisfaction level. METHOD: A cross-sectional study was
      conducted using selfadministered questionnaires distributed to a convenience
      sample of the general public in Kedah, Malaysia. RESULTS: A total of 435 out of
      500 people invited to participate in the study agreed to take part, giving a
      response rate of 87 per cent. In this study, only approximately half of the
      participants (n=198, 45.5 per cent) were fully satisfied with the current
      healthcare services. The majority of the participants agreed that doctors had
      given enough information about their state of health (n=222, 51 per cent) and
      were competent and sympathetic (n=231, 53.1 per cent). Almost half of the
      participants (n=215, 49.5 per cent) agreed that the doctors took their problems
      seriously. Only 174 (40 per cent) participants agreed that doctors had spent
      enough time on their consultation session. Some respondents (n=266, 61.2 per
      cent) agreed that healthcare professionals in the public health sector were
      highly skilled. The majority of the respondents described amenities,
      accessibility and facilities available in the public healthcare sector as good or
      better. In this study, waiting time was significantly associated with patient
      satisfaction as the results showed that those who waited longer than two hours
      were less satisfied with the services than those who waited under two hours.
      CONCLUSION: The study findings showed that approximately half of the respondents
      were fully satisfied with current healthcare services. In this study, waiting
      time was the main factor that affected patient satisfaction level. Other factors
      that influenced satisfaction level included the length of consultation sessions
      and the process of patient registration. Hence, improvement in the health
      services that leads to a shorter waiting time may increase the satisfaction level
      of patients.

PMID- 24567766
TI  - The current state of diabetes mellitus in India.

PMID- 24567767
TI  - The Qualitative Hyperalgesia Profile: A New Metric to Assess Chronic Post
      Thoracotomy Pain.
AB  - Thoracotomy often results in chronic pain, characterized by resting pain and
      elevated mechano-sensitivity. This paper defines complex behavioral responses to
      tactile stimulation in rats after thoracotomy, shown to be reversibly relieved by
      systemic morphine, in order to develop a novel qualitative "pain" score. A deep
      incision and 1 hour of rib retraction in male Sprague-Dawley rats resulted in
      reduced threshold and a change in the locus of greatest tactile (von Frey
      filament) sensitivity, from the lower back to a more rostral location around the
      wound site, and extending bilaterally. The fraction of rats showing nocifensive
      responses to mild stimulation (10 gm) increased after thoracotomy (from a pre
      operative value of 0/10 to 8/10 at 10 days post-op), and the average threshold
      decreased correspondingly, from 15 gm to ~4 gm. The nature of the nocifensive
      responses to tactile stimulation, composed pre-operatively only of no response
      (Grade 0) or brief contractions of the local subcutaneous muscles (Grade I),
      changed markedly after thoracotomy, with the appearance of new behaviors
      including a brisk lateral "escape" movement and/or a 180 degrees  rotation of the
      trunk (both included as Grade II), and whole body shuddering, and scratching and
      squealing (Grade III). Systemic morphine (2.5 mg/kg, i.p.) transiently raised the
      threshold for response and reduced the frequency of Grade II and III responses,
      supporting the interpretation that these represent pain. The findings support the
      development of a Qualitative Hyperalgesic Profile to assess the complex behavior
      that indicates a central integration of hyperalgesia.

PMID- 24567770
TI  - MRI findings of a remote and isolated vaginal metastasis revealing an
      adenocarcinoma of the mid-sigmoid colon.
AB  - A remote vaginal metastasis from a colo-rectal carcinoma is extremely rare. Only
      few cases have been described in the literature. The radiological appearances of
      a vaginal metastasis from colon-rectal cancer have not been extensively
      investigated. We report the MRI findings with clinical and pathological
      correlations of a remote and isolated vaginal metastasis revealing a mid-sigmoid
      adenocarcinoma in a 67 years old woman. 

PMID- 24567769
TI  - Congenital vascular malformations in scintigraphic evaluation.
AB  - BACKGROUND: Congenital vascular malformations are tumour-like, non-neoplastic
      lesions caused by disorders of vascular tissue morphogenesis. They are
      characterised by a normal cell replacement cycle throughout all growth phases and
      do not undergo spontaneous involution. Here we present a scintigraphic image of
      familial congenital vascular malformations in two sisters. MATERIAL/METHODS: A 17
      years-old young woman with a history of multiple hospitalisations for foci of
      vascular anomalies appearing progressively in the upper and lower right limbs,
      chest wall and spleen. A Parkes Weber syndrome was diagnosed based on the
      clinical picture. Due to the occurrence of new foci of malformations, a whole
      body scintigraphic examination was performed. A 12-years-old girl reported a lump
      in the right lower limb present for approximately 2 years, which was clinically
      identified as a vascular lesion in the area of calcaneus and talus.
      Phleboscintigraphy visualized normal radiomarker outflow from the feet via the
      deep venous system, also observed in the superficial venous system once the
      tourniquets were released. In static and whole-body examinations vascular
      malformations were visualised in the area of the medial cuneiform, navicular and
      talus bones of the left foot, as well as in the projection of right calcaneus and
      above the right talocrural joint. CONCLUSIONS: People with undiagnosed disorders
      related to the presence of vascular malformations should undergo periodic follow
      up to identify lesions that may be the cause of potentially serious complications
      and to assess the results of treatment. Presented scintigraphic methods may be
      used for both diagnosing and monitoring of disease progression.

PMID- 24567768
TI  - Misfolding of Mutated Vasopressin Causes ER-Retention and Activation of ER-Stress
      Markers in Neuro-2a Cells.
AB  - Arginine-vasopressin (AVP) is a peptide hormone normally secreted from
      neuroendocrine cells via the regulated secretory pathway. In Familial
      Neurohypophyseal Diabetes Insipidus (FNDI), an autosomal dominant form of central
      diabetes insipidus, mutations of pro-vasopressin appear to accumulate in the
      endoplasmic reticulum (ER) causing a lack of biologically active AVP in the
      blood. To investigate the effect of pro-vasopressin mutations regarding
      intracellular functions of protein targeting and secretion, we created two FNDI
      associated amino acid substitution mutants, e.g., G14R, and G17V in frame with
      green fluorescent protein (GFP) and pro-vasopressin (VP) in frame with red
      fluorescent protein (VP-RFP). Fluorescence microscopy of Neuro-2a cells
      expressing these constructs revealed co-localization of VP-GFP and VP-RFP to
      punctate granules along the length and accumulating at the tips of neurites,
      characteristic of regulated secretory granules. In contrast, the two FNDI
      associated amino acid substitution mutants, e.g., G14R-GFP, and G17VGFP, were
      localized to a perinuclear region of the Neuro-2a cells characteristic of the
      endoplasmic reticulum. Co-expression of these mutants with VP-RFP showed VP-RFP
      was retained in the ER, co-localized with the mutants suggesting the formation of
      heterodimers as found in FNDI. Stimulated secretion experiments indicated that VP
      GFP was secreted in an inducible manner whereas, G14R-GFP and G17V-GFP were
      retained to nearly 100% within the cells. Analysis by western blotting and semi
      quantitative RT-PCR indicated an increased protein and mRNA expression for an ER
      resident molecular chaperone, BiP. Further analysis of ER-storage disease
      associated proteins such as caspase 12 and CHOP showed an increase in these as
      well. The results suggest that G14R-GFP and G17V-GFP are retained in the ER of
      Neuro-2a cells, resulting in up-regulation of the molecular chaperone BiP, and
      activation of the ER-storage disease-associated caspase cascade system.

PMID- 24567771
TI  - Evaluation of options for large scalp defect reconstruction: a 12-year
      experience.
AB  - OBJECTIVE: Multiple options for reconstruction of scalp defects exist with local
      tissue advancement and free tissue transfer the mainstay of reconstruction. Over
      the last 12 years, our tertiary referral hospital has performed more than 150
      scalp reconstructions. We reviewed our experience with large scalp defects and
      evaluated whether free tissue transfer is a viable first option for
      reconstruction. METHODS: A retrospective review was conducted of all scalp
      reconstructions from January 1, 1999, to December 31, 2011. A cohort of patients
      with defects greater than 50 cm(2) were identified for a total of 64 operations;
      10 free flaps, 28 local advancement flaps, and 26 skin grafts. Reoperation rates
      and complications were compared between groups. RESULTS: Reoperation rate in the
      free flap group was 20% (2/10). Both reoperations were within the immediate
      postoperative period, one for microvascular thrombotic occlusion and the other
      for postoperative hematoma. The local tissue transfer group had a 14% reoperation
      rate (4/28), all for debridement of partial flap loss. The skin graft cohort had
      a 12% reoperation rate (3/26) for 1 complete and 2 partial skin graft failures;
      all required repeat grafting. Reoperation for free-flap complications did not
      require rehospitalization. In contrast, the skin graft and non-free flap
      reoperations frequently required rehospitalization. CONCLUSION: Though free
      tissue transfer has a higher occurrence of reoperation within the immediate
      postoperative period, completion of reconstruction usually occurs within a single
      hospitalization. Free tissue transfer is a feasible option, and we advocate for
      its use as a primary method for repairing large scalp defects.

PMID- 24567772
TI  - Vertical stratification in arthropod spatial distribution research.
AB  - Spatial heterogeneity within individual host trees is often overlooked in surveys
      of phytophagous arthropod abundance and distribution. The armored scale
      Aulacaspis yasumatsui is controlled by the predator Rhyzobius lophanthae to a
      greater degree on leaves at 75-cm height than on leaves at ground level within
      its host tree Cycas micronesica. The direct influence of elevation on the
      predator indirectly generates vertical heterogeneity of the scale insect.
      Arthropod sampling schemes that fail to include all strata within the vertical
      profile of the host tree species may generate misleading outcomes. Results
      indicate that sub-meter increments can reveal significant differences in vertical
      distribution of phytophagous insects, and that inclusion of observations on other
      organisms that interact with the target arthropod may illuminate determinants of
      vertical heterogeneity. 

PMID- 24567773
TI  - A zinc transporter gene required for development of the nervous system.
AB  - The essentiality of zinc for normal brain development is well established. It has
      been suggested that primary and secondary zinc deficiencies can contribute to the
      occurrence of numerous human birth defects, including many involving the central
      nervous system. In a recent study, we searched for zinc transporter genes that
      were critical for neurodevelopment. We confirmed that ZIP12 is a zinc transporter
      encoded by the gene slc39a12 that is highly expressed in the central nervous
      systems of human, mouse, and frog (Xenopus tropicalis).Using loss-of-function
      methods, we determined that ZIP12 is required for neuronal differentiation and
      neurite outgrowth and necessary for neurulation and embryonic viability. These
      results highlight an essential need for zinc regulation during embryogenesis and
      nervous system development. We suggest that slc39a12 is a candidate gene for
      inherited neurodevelopmental defects in humans. 

PMID- 24567774
TI  - Tubulin polymerization promoting protein 1 (TPPP1): A DNA-damage induced
      microtubule regulatory gene.
AB  - The eukaryotic cell cycle relies heavily on the mechanical forces vested by the
      dynamic rearrangement of the microtubule (MT) network. Tubulin Polymerization
      promoting Protein 1 (TPPP1) alters MT dynamics by driving MT polymerization as
      well as stabilization, via increasing MT acetylation. It increases MT rigidity,
      which results in reduced cell proliferation through downregulation of G1/S-phase
      and mitosis to G1-phase cell cycle transitioning. In this communication, we
      provide further evidence that TPPP1 may be an important regulator of genomic
      homeostasis. Our preliminary data show that long-term TPPP1 overexpression
      reduces cell viability via induction of apoptotic cell death pathways. Moreover,
      induction of DNA-damage results in increased TPPP1 expression, which is inhibited
      in the absence of expression of the tumor suppressor p53. 

PMID- 24567775
TI  - Matricellular protein Cfl1 regulates cell differentiation.
AB  - Like higher eukaryotic cells in tissues, microbial cells in a community act in
      concert in response to environmental stimuli. They coordinate gene expression and
      their physiological and morphological states through intercellular communication
      mediated by matricellular signals. The adhesion protein Cfl1 was recently shown
      to be a matricellular signal in regulating morphogenesis and biofilm formation in
      the eukaryotic microbe Cryptococcus neoformans. Cfl1 is naturally highly
      expressed in the hyphal subpopulation during the mating colony development. Some
      Cfl1 proteins are cleaved and released to the ECM (extracellular matrix). The
      released exogenous Cfl1 activates Cryptococcus cells to express their endogenous
      Cfl1, to undergo filamentation, and to form structured biofilm colonies. In this
      study, we demonstrate that the N-terminal signal peptide and the novel conserved
      cysteine-rich SIGC domain at the C-terminus are critical for the adherence
      property and the signaling activity of this multifunctional protein. The
      investigation of this fungal matricellular signaling network involving Cfl1 and
      the master regulator of morphogenesis Znf2 provides a foundation to further
      elucidate intercellular communication in microbial development. 

PMID- 24567776
TI  - Stem cell therapy without the cells.
AB  - As an example of the burgeoning importance of stem cell therapy, this past month
      the California Institute for Regenerative Medicine (CIRM) has approved $70
      million to create a new network of stem cell clinical trial centers. Much work in
      the last decade has been devoted to developing the use of autologous and
      allogeneic adult stem cell transplants to treat a number of conditions, including
      heart attack, dementia, wounds, and immune system-related diseases. The standard
      model teaches us that adult stem cells exists throughout most of the body and
      provide a means to regenerate and repair most tissues through replication and
      differentiation. Although we have often witnessed the medical cart placed in
      front of the scientific horse in the development of stem cell therapies outside
      of academic circles, great strides have been made, such as the use of purified
      stem cells(1) instead of whole bone marrow transplants in cancer patients, where
      physicians avoid re-injecting the patients with their own cancer cells.(2) We
      most often think of stem cell therapy acting to regenerate tissue through
      replication and then differentiation, but recent studies point to the dramatic
      effects adult stem cells exert in the repair of various tissues through the
      release of paracrine and autocrine substances, and not simply through
      differentiation. Indeed, up to 80% of the therapeutic effect of adult stem cells
      has been shown to be through paracrine mediated actions.(3) That is, the
      collected types of molecules released by the stem cells, called the secretome, or
      stem cell released molecules (SRM), number in the 100s, including proteins,
      microRNA, growth factors, antioxidants, proteasomes, and exosomes, and target a
      multitude of biological pathways through paracrine actions. The composition of
      the different molecule types in SRM is state dependent, and varies with cell type
      and conditions such as age and environment. 

PMID- 24567777
TI  - Dapper Antagonist of Catenin-1 (Dact1) contributes to dendrite arborization in
      forebrain cortical interneurons.
AB  - In mice, genetically engineered knockout of the Dapper Antagonist of Catenin-1
      (Dact1) locus, which encodes a scaffold protein involved in Wnt signaling, leads
      to decreased excitatory input formation on dendrites of developing forebrain
      neurons. We have previously demonstrated this in both (excitatory, glutamatergic)
      pyramidal neurons of the hippocampus and in (inhibitory GABAergic) interneurons
      of the cortex. We have also demonstrated that knockout of the Dact1 locus leads
      to decreased dendrite complexity in cultured hippocampal pyramidal neurons, and
      to decreased spine formation on dendrites of forebrain pyramidal neurons in vitro
      and in vivo. Synapse phenotypes resulting from Dact1 loss in cultured cortical
      interneurons can be rescued by recombinant overexpression of the Dact1 binding
      partner, Dishevelled-1 (Dvl1), but not by recombinant expression of a
      constitutively active form of the small GTPase Rac1. This contrasts with dendrite
      spine phenotypes resulting from Dact1 loss in cultured hippocampal pyramidal
      neurons, which can be fully rescued by recombinant expression of activated Rac1.
      Taken together, these data suggest that in maturing forebrain neurons there are
      molecularly separate requirements for Dact1 in dendrite arborization/spine
      formation vs. synaptogenesis. Here, we show that the developmental requirement
      for Dact1 during dendrite arborization, which we previously demonstrated only in
      hippocampal pyramidal neurons, is also present in cortical interneurons, and we
      discuss mechanistic implications of this finding. 

PMID- 24567778
TI  - The intersection of a military culture and indigenous peoples in conservation
      issues.
AB  - Military operations impose various positive and negative consequences on the
      environment. Three case studies are presented illuminating how local indigenous
      peoples as stakeholders may be vulnerable to being disenfranchised from important
      discussions concerning military activities. The study of ecological issues
      associated with sustaining a military footprint may be particularly useful for
      informing the global debate that pits strict conservation against human well
      being. 

PMID- 24567779
TI  - The different types of sperm morphology and behavior within a single species: Why
      do sperm of squid sneaker males form a cluster?
AB  - Some coastal squids exhibit male dimorphism (large and small body size) that is
      linked to mating behaviors. Large "consort" males compete with other, rival males
      to copulate with a female, and thereby transfer their spermatophores to her
      internal site around the oviduct. Small "sneaker" males rush to a single female
      or copulating pair and transfer spermatophores to her external body surface
      around the seminal receptacle near the mouth. We previously found that in Loligo
      bleekeri, sneaker sperm are ~50% longer than consort sperm, and only the sneaker
      sperm, once ejaculated from the spermatophore (sperm mass), form a cluster
      because of chemoattraction toward their own respiratory CO2. Here, we report that
      sperm clusters are able to move en masse. Because a fraction of ejaculated sperm
      from a sneaker's spermatophore are eventually located in the female's seminal
      receptacle, we hypothesize that sperm clustering facilitates collective migration
      to the seminal receptacle or an egg micropyle. Sperm clustering is regarded as a
      cooperative behavior that may have evolved by sperm competition and/or physical
      and physiological constraints imposed by male mating tactics. 

PMID- 24567780
TI  - Doing the math: How yeast cells maintain their peroxisome populations.
AB  - The formation of membrane contact sites between cellular organelles is required
      for proper organelle communication and maintenance in the compartmentalized
      eukaryotic cell. We recently identified a tether that links peroxisomes to the
      cortical ER in the yeast, Saccharomyces cerevisiae. The tether is made up of the
      peroxisome biogenic protein Pex3p and the peroxisome inheritance factor Inp1p,
      and is formed by Inp1p-mediated linkage of ER-bound Pex3p and peroxisomal Pex3p.
      Here we discuss how this tether is fine-tuned to ensure that peroxisomes are
      stably maintained over generations of yeast cells. 

PMID- 24567781
TI  - Mitochondrial inheritance is mediated by microtubules in mammalian cell division.
AB  - The mitochondrial network fragments and becomes uniformly dispersed within the
      cytoplasm when mammalian cells enter mitosis. Such morphology and distribution of
      mitochondria was previously thought to facilitate the stochastic inheritance of
      mitochondria by daughter cells. In contrast, we recently reported that
      mitochondria in dividing mammalian cells are inherited by an ordered mechanism of
      inheritance mediated by microtubules. We showed that mitochondria are
      progressively enriched at the cell equator and depleted at the poles throughout
      division. Furthermore, the mitochondrial distribution during division is
      dependent on microtubules, indicating an ordered inheritance strategy. The
      microtubule-mediated positioning of mitochondria in dividing mammalian cells may
      have functional consequences for cell division and/or mitochondrial inheritance. 

PMID- 24567782
TI  - From ethnopharmacology to drug design.
AB  - Nature's diversity is one of the biggest resources of therapeutic lead compounds.
      Traditionally-used herbal remedies harbor a variety of bioactive compounds
      providing researchers with starting points for drug development.
      Ethnopharmacological investigations of uterotonic plant preparations identified a
      class of circular and disulfide-rich peptides, called cyclotides, to exhibit
      strong uterine contractions. In humans one of the physiological regulators of the
      myometrial contractility is the nonapeptide oxytocin acting on its cognate G
      protein-coupled receptors. They are considered to represent one of the most
      promising drug targets with ~30% of all currently marketed drugs acting on these
      transmembrane receptors. Based on observed similarities regarding the activity
      and structure of plant cyclotides with human oxytocin we analyzed the
      pharmacological principle of their action and identified the oxytocin and
      vasopressin 1a receptors as molecular targets of cyclotides from the Rubiaceae
      plant Oldenlandia affinis. Using a synthetic approach, the sequence of the native
      cyclotide kalata B7 was used to design oxytocin-like nonapeptides with nanomolar
      affinity and selectivity for the oxytocin receptor. This provides formal proof
      for the use of cyclotides as templates in peptide ligand design. At a more
      general level, mining of naturally-occurring peptides is a promising tool for the
      identification and the design of novel G protein-coupled receptor ligands. 

PMID- 24567783
TI  - Dendritic cells derived from pluripotent stem cells: Potential of large scale
      production.
AB  - Human pluripotent stem cells (hPSCs), including human embryonic stem cells and
      human induced pluripotent stem cells, are promising sources for hematopoietic
      cells due to their unlimited growth capacity and the pluripotency. Dendritic
      cells (DCs), the unique immune cells in the hematopoietic system, can be loaded
      with tumor specific antigen and used as vaccine for cancer immunotherapy. While
      autologous DCs from peripheral blood are limited in cell number, hPSC-derived DCs
      provide a novel alternative cell source which has the potential for large scale
      production. This review summarizes recent advances in differentiating hPSCs to
      DCs through the intermediate stage of hematopoietic stem cells. Step-wise growth
      factor induction has been used to derive DCs from hPSCs either in suspension
      culture of embryoid bodies (EBs) or in co-culture with stromal cells. To fulfill
      the clinical potential of the DCs derived from hPSCs, the bioprocess needs to be
      scaled up to produce a large number of cells economically under tight quality
      control. This requires the development of novel bioreactor systems combining
      guided EB-based differentiation with engineered culture environment. Hence,
      recent progress in using bioreactors for hPSC lineage-specific differentiation is
      reviewed. In particular, the potential scale up strategies for the multistage DC
      differentiation and the effect of shear stress on hPSC differentiation in
      bioreactors are discussed in detail. 

PMID- 24567784
TI  - Neural differentiation from pluripotent stem cells: The role of natural and
      synthetic extracellular matrix.
AB  - Neural cells differentiated from pluripotent stem cells (PSCs), including both
      embryonic stem cells and induced pluripotent stem cells, provide a powerful tool
      for drug screening, disease modeling and regenerative medicine. High-purity
      oligodendrocyte progenitor cells (OPCs) and neural progenitor cells (NPCs) have
      been derived from PSCs recently due to the advancements in understanding the
      developmental signaling pathways. Extracellular matrices (ECM) have been shown to
      play important roles in regulating the survival, proliferation, and
      differentiation of neural cells. To improve the function and maturation of the
      derived neural cells from PSCs, understanding the effects of ECM over the course
      of neural differentiation of PSCs is critical. During neural differentiation of
      PSCs, the cells are sensitive to the properties of natural or synthetic ECMs,
      including biochemical composition, biomechanical properties, and
      structural/topographical features. This review summarizes recent advances in
      neural differentiation of human PSCs into OPCs and NPCs, focusing on the role of
      ECM in modulating the composition and function of the differentiated cells.
      Especially, the importance of using three-dimensional ECM scaffolds to simulate
      the in vivo microenvironment for neural differentiation of PSCs is highlighted.
      Future perspectives including the immediate applications of PSC-derived neural
      cells in drug screening and disease modeling are also discussed. 

PMID- 24567785
TI  - Role of mesenchymal stem cells in cell life and their signaling.
AB  - Mesenchymal stem cells (MSCs) have various roles in the body and cellular
      environment, and the cellular phenotypes of MSCs changes in different conditions.
      MSCs support the maintenance of other cells, and the capacity of MSCs to
      differentiate into several cell types makes the cells unique and full of
      possibilities. The involvement of MSCs in the epithelial-mesenchymal transition
      is an important property of these cells. In this review, the role of MSCs in cell
      life, including their application in therapy, is first described, and the
      signaling mechanism of MSCs is investigated for a further understanding of these
      cells. 

PMID- 24567786
TI  - Distinction of white, beige and brown adipocytes derived from mesenchymal stem
      cells.
AB  - Adipose tissue is a major metabolic organ, and it has been traditionally
      classified as either white adipose tissue (WAT) or brown adipose tissue (BAT).
      WAT and BAT are characterized by different anatomical locations, morphological
      structures, functions, and regulations. WAT and BAT are both involved in energy
      balance. WAT is mainly involved in the storage and mobilization of energy in the
      form of triglycerides, whereas BAT specializes in dissipating energy as heat
      during cold- or diet-induced thermogenesis. Recently, brown-like adipocytes were
      discovered in WAT. These brown-like adipocytes that appear in WAT are called
      beige or brite adipocytes. Interestingly, these beige/brite cells resemble white
      fat cells in the basal state, but they respond to thermogenic stimuli with
      increased levels of thermogenic genes and increased respiration rates. In
      addition, beige/brite cells have a gene expression pattern distinct from that of
      either white or brown fat cells. The current epidemic of obesity has increased
      the interest in studying adipocyte formation (adipogenesis), especially in
      beige/brite cells. This review summarizes the developmental process of adipose
      tissues that originate from the mesenchymal stem cells and the features of these
      three different types of adipocytes. 

PMID- 24567787
TI  - Brain stem cells as the cell of origin in glioma.
AB  - Glioma incidence rates in the United States are near 20000 new cases per year,
      with a median survival time of 14.6 mo for high-grade gliomas due to limited
      therapeutic options. The origins of these tumors and their many subtypes remain a
      matter of investigation. Evidence from mouse models of glioma and human clinical
      data have provided clues about the cell types and initiating oncogenic mutations
      that drive gliomagenesis, a topic we review here. There has been mixed evidence
      as to whether or not the cells of origin are neural stem cells, progenitor cells
      or differentiated progeny. Many of the existing murine models target cell
      populations defined by lineage-specific promoters or employ lineage-tracing
      methods to track the potential cells of origin. Our ability to target specific
      cell populations will likely increase concurrently with the knowledge gleaned
      from an understanding of neurogenesis in the adult brain. The cell of origin is
      one variable in tumorigenesis, as oncogenes or tumor suppressor genes may
      differentially transform the neuroglial cell types. Knowledge of key driver
      mutations and susceptible cell types will allow us to understand cancer biology
      from a developmental standpoint and enable early interventional strategies and
      biomarker discovery. 

PMID- 24567789
TI  - Current applications of adipose-derived stem cells and their future perspectives.
AB  - Adult stem cells have a great potential to treat various diseases. For these cell
      based therapies, adipose-derived stem cells (ADSCs) are one of the most promising
      stem cell types, including embryonic stem cells (ESCs) and induced pluripotent
      stem cells (iPSCs). ESCs and iPSCs have taken center stage due to their
      pluripotency. However, ESCs and iPSCs have limitations in ethical issues and in
      identification of characteristics, respectively. Unlike ESCs and iPSCs, ADSCs do
      not have such limitations and are not only easily obtained but also uniquely
      expandable. ADSCs can differentiate into adipocytes, osteoblasts, chondrocytes,
      myocytes and neurons under specific differentiation conditions, and these kinds
      of differentiation potential of ADSCs could be applied in regenerative medicine
      e.g., skin reconstruction, bone and cartilage formation, etc. In this review, the
      current status of ADSC isolation, differentiation and their therapeutic
      applications are discussed. 

PMID- 24567788
TI  - An overview of the role of cancer stem cells in spine tumors with a special focus
      on chordoma.
AB  - Primary malignant tumors of the spine are relatively rare, less than 5% of all
      spinal column tumors. However, these lesions are often among the most difficult
      to treat and encompass challenging pathologies such as chordoma and a variety of
      invasive sarcomas. The mechanisms of tumor recurrence after surgical
      intervention, as well as resistance to radiation and chemotherapy, remain a
      pervasive and costly problem. Recent evidence has emerged supporting the
      hypothesis that solid tumors contain a sub-population of cancer cells that
      possess characteristics normally associated with stem cells. Particularly, the
      potential for long-term proliferation appears to be restricted to subpopulations
      of cancer stem cells (CSCs) functionally defined by their capacity to self-renew
      and give rise to differentiated cells that phenotypically recapitulate the
      original tumor, thereby causing relapse and patient death. These cancer stem
      cells present a unique opportunity to better understand the biology of solid
      tumors in general, as well as targets for future therapeutics. The general
      objective of the current study is to discuss the fundamental concepts for
      understanding the role of CSCs with respect to chemoresistance, radioresistance,
      special cell surface markers, cancer recurrence and metastasis in tumors of the
      osseous spine. This discussion is followed by a specific review of what is known
      about the role of CSCs in chordoma, the most common primary malignant osseous
      tumor of the spine. 

PMID- 24567790
TI  - Modern approach to cholecysto-choledocholithiasis.
AB  - Gallstones and common bile duct calculi are found to be associated in 8%-20% of
      patients, leading to possible life-threatening complications, such as acute
      biliary pancreatitis, jaundice and cholangitis. The gold standard of care for
      gallbladder calculi and isolated common bile duct stones is represented by
      laparoscopic cholecystectomy and endoscopic retrograde cholangiopancreatography,
      respectively, while a debate still exists regarding how to treat the two diseases
      at the same time. Many therapeutic options are also available when the two
      conditions are associated, including many different types of treatment, which
      local professionals often administer. The need to limit maximum discomfort and
      risks for the patients, combined with the economic pressure of reducing costs and
      utilizing resources, favors single-step procedures. However, a multitude of data
      fail to strongly demonstrate the superiority of any technique (including a two or
      multi-step approach), while rigorous clinical trials that include so many
      different types of treatment are still lacking, and it is most likely unrealistic
      to conduct them in the future. Therefore, the choice of the best management is
      often led by the local presence of professional expertise and resources, rather
      than by a real superiority of one strategy over another. 

PMID- 24567791
TI  - Transnasal endoscopy: Technical considerations, advantages and limitations.
AB  - Transnasal endoscopy (TNE) is an upper endoscopy method which is performed by the
      nasal route using a thin endoscope less than 6 mm in diameter. The primary goal
      of this method is to improve patient tolerance and convenience of the procedure.
      TNE can be performed without sedation and thus eliminates the risks associated
      with general anesthesia. In this way, TNE decreases the cost and total duration
      of endoscopic procedures, while maintaining the image quality of standard caliber
      endoscopes, providing good results for diagnostic purposes. However, the small
      working channel of the ultra-thin endoscope used for TNE makes it difficult to
      use for therapeutic procedures except in certain conditions which require a
      thinner endoscope. Biopsy is possible with special forceps less than 2 mm in
      diameter. Recently, TNE has been used for screening endoscopy in Far East Asia,
      including Japan. In most controlled studies, TNE was found to have better patient
      tolerance when compared to unsedated endoscopy. Nasal pain is the most
      significant symptom associated with endoscopic procedures but can be reduced with
      nasal pretreatment. Despite the potential advantage of TNE, it is not common in
      Western countries, usually due to a lack of training in the technique and a lack
      of awareness of its potential advantages. This paper briefly reviews the
      technical considerations as well as the potential advantages and limitations of
      TNE with ultra-thin scopes. 

PMID- 24567792
TI  - Endoscopic management and prevention of migrated esophageal stents.
AB  - The use of self-expandable metallic stents has increased recently to palliate
      inoperable esophageal neoplasia and also in the management of benign strictures.
      Migration is one of the most common complications after stent placement and the
      endoscopist should be able to recognize and manage this situation. Several
      techniques for managing migrated stents have been described, as well as new
      techniques for preventing stent migration. Most stents have a "lasso" at the
      upper flange which facilitates stent repositioning or removal. An overtube,
      endoloop and large polypectomy snare may be useful for the retrieval of stents
      migrated into the stomach. External fixation of the stent with Shim's technique
      is efficient in preventing stent migration. Suturing the stent to the esophageal
      wall, new stent designs with larger flanges and double-layered stents are
      promising techniques to prevent stent migration but they warrant validation in a
      larger cohort of patients. 

PMID- 24567793
TI  - An automated spring-loaded needle for endoscopic ultrasound-guided abdominal
      paracentesis in cancer patients.
AB  - AIM: To evaluate the feasibility of using an automated spring-loaded needle
      device for endoscopic ultrasound (EUS)-guided abdominal paracentesis (EUS-P) to
      see if this would make it easier to puncture the mobile and lax gastric wall for
      EUS-P. METHODS: The EUS database and electronic medical records at Fukushima
      Medical University Hospital were searched from January 2001 to April 2011.
      Patients with a history of cancer and who underwent EUS-P using an automated
      spring-loaded needle device with a 22-gauge puncture needle were included. The
      needle was passed through the instrument channel and advanced through the
      gastrointestinal wall under EUS guidance into the echo-free space in the
      abdominal cavity and ascitic fluid was collected. The confirmed diagnosis of
      malignant ascites included positive cytology and results from careful clinical
      observation for at least 6 mo in patients with negative cytology. The technical
      success rate, cytology results and complications were evaluated. RESULTS: We
      found 11 patients who underwent EUS-P with an automated spring-loaded needle
      device. In 4 cases, ascites was revealed only with EUS but not in other imaging
      modalities. EUS-P was done in 7 other cases because there was minimal ascitic
      fluid and no safe window for percutaneous abdominal aspiration. Ascitic fluid was
      obtained in all cases by EUS-P. The average amount aspirated was 14.1 mL (range
      0.5-38 mL) and that was sent for cytological exam. The etiology of ascitic fluid
      was benign in 5 patients and malignant in 6. In all cases, ascitic fluid was
      obtained with the first needle pass. No procedure-related adverse effects
      occurred. CONCLUSION: EUS-P with an automated spring-loaded needle device is a
      feasible and safe method for ascites evaluation.

PMID- 24567794
TI  - Thrombocytosis as a prognostic marker in gastrointestinal cancers.
AB  - Thrombocytosis is an adverse prognostic factor in many types of cancer. These
      include breast cancer, ovarian and other gynecologic cancers, renal cell
      carcinoma and lung cancers. In gastrointestinal cancers of various locations and
      histologic types, thrombocytosis has been reported in general to be associated
      with adverse clinical outcomes. Platelet count measurement is well standardized
      and available in every clinical laboratory, making its use as a prognostic marker
      practical. This paper will discuss the data on the prognostic value of
      thrombocytosis in gastrointestinal cancers as well as pathogenic aspects of the
      association that strengthen the case for its use in clinical prognostication. 

PMID- 24567796
TI  - Extended cancer-free survival after palliative chemoradiation for metastatic
      esophageal cancer.
AB  - We report on a patient who remained cancer-free for an extended time after
      palliative radiotherapy (RT) and chemotherapy (nedaplatin plus 5-fluorouracil)
      treatment for stage IV (cT3N3M1) esophageal squamous cell carcinoma. Although
      multiple lymph nodes outside the RT field recurred, the local primary tumor
      within the RT field did not recur, even 17 mo after palliative RT of 30 Gy in 10
      fractions. In this case, acute toxicity, such as myelosuppression or esophagitis,
      was not enhanced by increasing the fraction dose from 1.8-2.0 Gy to 3.0 Gy.
      Because 30 Gy in 10 fractions can be completed within a shorter time and is less
      expensive than 50.4 Gy in 28 fractions, we think that 30 Gy without oblique beams
      is a more favorable RT method for patients. 

PMID- 24567795
TI  - Mechanisms linking dietary fiber, gut microbiota and colon cancer prevention.
AB  - Many epidemiological and experimental studies have suggested that dietary fiber
      plays an important role in colon cancer prevention. These findings may relate to
      the ability of fiber to reduce the contact time of carcinogens within the
      intestinal lumen and to promote healthy gut microbiota, which modifies the host's
      metabolism in various ways. Elucidation of the mechanisms by which dietary fiber
      dependent changes in gut microbiota enhance bile acid deconjugation, produce
      short chain fatty acids, and modulate inflammatory bioactive substances can lead
      to a better understanding of the beneficial role of dietary fiber. This article
      reviews the current knowledge concerning the mechanisms via which dietary fiber
      protects against colon cancer. 

PMID- 24567798
TI  - Insulin and bone: Recent developments.
AB  - While insulin-like growth factor I is a well-known anabolic agent in bone
      evidence is beginning to accumulate that its homologue, insulin, also has some
      anabolic properties for bone. There is specific evidence that insulin may work to
      stimulate osteoblast differentiation, which in turn would enhance production of
      osteocalcin, the osteoblast-produced peptide that can stimulate pancreatic beta
      cell proliferation and skeletal muscle insulin sensitivity. It is uncertain
      whether insulin stimulates bone directly or indirectly by increasing muscle work
      and therefore skeletal loading. We raise the question of the sequence of events
      that occurs with insulin resistance, such as type 2 diabetes. Evidence to date
      suggests that these patients have lower serum concentrations of osteocalcin,
      perhaps reduced skeletal loading, and reduced bone strength as evidenced by micro
      indentation studies. 

PMID- 24567797
TI  - Excess vitamin intake: An unrecognized risk factor for obesity.
AB  - Over the past few decades, food fortification and infant formula supplementation
      with high levels of vitamins have led to a sharp increase in vitamin intake among
      infants, children and adults. This is followed by a sharp increase in the
      prevalence of obesity and related diseases, with significant disparities among
      countries and different groups within a country. It has long been known that B
      vitamins at doses below their toxicity threshold strongly promote body fat gain.
      Studies have demonstrated that formulas, which have very high levels of vitamins,
      significantly promote infant weight gain, especially fat mass gain, a known risk
      factor for children developing obesity. Furthermore, ecological studies have
      shown that increased B vitamin consumption is strongly correlated with the
      prevalence of obesity and diabetes. We therefore hypothesize that excess vitamins
      may play a causal role in the increased prevalence of obesity. This review will
      discuss: (1) the causes of increased vitamin intake; (2) the non-monotonic effect
      of excess vitamin intake on weight and fat gain; and (3) the role of vitamin
      fortification in obesity disparities among countries and different groups within
      a country. 

PMID- 24567800
TI  - Insulin plus incretin: A glucose-lowering strategy for type 2-diabetes.
AB  - There are many advantages of combining incretin therapy [glucagon-like peptide-1
      (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors] with
      insulin therapy as a glucose-lowering strategy in type 2 diabetes. One important
      advantage is the complementary mode of the mechanistic action of incretin and
      insulin therapy. Another advantage is the reduction in risk of hypoglycemia and
      weight gain when adding incretin therapy to insulin. Several clinical trials have
      studied the addition of GLP-1 receptor agonists [exenatide BID (twice daily),
      lixisenatide, albiglutide] or DPP-4 inhibitors (vildagliptin, sitagliptin,
      saxagliptin, alogliptin, linagliptin) to ongoing insulin therapy or adding
      insulin to ongoing therapy with a GLP-1 receptor agonist (liraglutide). These
      studies show improved glycemia in the presence of limited risk for hypoglycemia
      and weight gain with the combination of incretin therapy with insulin. This
      article reviews the background and clinical studies on this combination. 

PMID- 24567803
TI  - Starting glargine in insulin-naive type 2 diabetic patients based on body mass
      index is safe.
AB  - AIM: To evaluate the safety of four insulin titration algorithms in a homogeneous
      population of insulin-naive type 2 diabetic patients. METHODS: We conducted a 24
      wk, open, single-center study with 92 insulin-naive type 2 diabetes patients who
      failed treatment with one or two oral drugs. The patients were randomized to one
      of the four following algorithms: LANMET (n = 26) and LANMET PLUS (n = 22)
      algorithms, whose patients received a fixed initial insulin dose of 10 U, and
      DeGold (n = 23) and DeGold PLUS (n = 21) algorithms, whose patients' initial
      insulin dose was based on their body mass index (BMI). In addition, patients in
      the PLUS groups had their insulin titrated twice a week from 2 to 8 U. In the
      other two groups, the titration was also performed also twice a week, but in a
      fixed increments of 2 U. The target fasting glucose levels for both groups was
      100 mg/dL. RESULTS: There was no significant difference in efficacy parameters.
      There was no significant difference when comparing moderate hypoglycemia events
      in algorithms starting with a 10 U fixed dose and algorithms based on BMI.
      However, there was a significant increase in moderate hypoglycemia events among
      the PLUS treated patients when the LANMET and DeGold algorithms were compared
      with the 2 fast-titration PLUS algorithms. We observed 12 hypoglycemia events in
      the first group, which corresponded to 0.94 events/patient per year, and we
      observed 42 events in the second group, which corresponded to 2.81 events/patient
      per year (P < 0.037). No further significant differences were observed when other
      comparisons between the algorithms were carried out. CONCLUSION: Starting insulin
      glargine based on BMI is safe, but fast titration algorithms increase the risk of
      moderate hypoglycemia.

PMID- 24567804
TI  - Rationale, design and baseline patient characteristics of the optimal type 2
      diabetes management including benchmarking and standard treatment study in
      Greece.
AB  - AIM: To describe baseline data of the optimal type 2 diabetes management
      including benchmarking and standard treatment (OPTIMISE) study in Greece.
      METHODS: "Benchmarking" is the process of receiving feedback comparing one's
      performance with that of others. The OPTIMISE (NCT00681850) study is a
      multinational, multicenter study assessing, at a primary care level, whether
      using "benchmarking" can help to improve the quality of patient care, compared
      with a set of guideline-based reference values ("non-benchmarking"). In the Greek
      region, 797 outpatients (457 men, mean age 63.8 years) with type 2 diabetes were
      enrolled by 84 office-based physicians. Baseline characteristics of this
      population are presented. RESULTS: Hypertension was the most prevalent
      concomitant disorder (77.3%) and coronary heart disease was the most frequent
      macrovascular complication of diabetes (23.8%). Most patients were overweight or
      obese (body mass index 29.6 +/- 5 kg/m(2)), exhibiting mostly abdominal obesity
      (waist circumference 102.6 +/- 13.6 cm). Biguanides were the most prevalent
      prescribed drugs for the management of diabetes (70.1% of all prescriptions),
      whereas statins (93.5% of all prescriptions) and angiotensin receptor blockers
      (55.8% of all prescriptions) were the most prevalent prescribed drugs for
      hyperlipidemia and hypertension, respectively. Only 37.4% of patients were on
      aspirin. Despite treatment, pre-defined targets for fasting plasma glucose (< 110
      mg/dL), glycated hemoglobin (< 7%), systolic blood pressure (< 130 mmHg and < 125
      mmHg for patients with proteinuria) and low density lipoprotein cholesterol
      levels (< 100 mg/dL and < 70 mg/dL for patients with coronary heart disease) were
      reached in a relatively small proportion of patients (29%, 53%, 27% and 31%,
      respectively). In a Greek population with type 2 diabetes, the control of
      glycemia or concomitant disorders which increase cardiovascular risk remains
      poor. CONCLUSION: Despite relevant treatment, there is a poor control of
      diabetes, hypertension and hyperlipidemia in Greek outpatients with type 2
      diabetes.

PMID- 24567805
TI  - Two birds with one stone: palonosetron pretreatment.

PMID- 24567802
TI  - Identification and differentiation of PDX1 beta-cell progenitors within the human
      pancreatic epithelium.
AB  - AIM: To minimize the expansion of pancreatic mesenchymal cells in vitro and
      confirm that beta-cell progenitors reside within the pancreatic epithelium.
      METHODS: Due to mesenchymal stem cell (MSC) expansion and overgrowth, progenitor
      cells within the pancreatic epithelium cannot be characterized in vitro, though
      beta-cell dedifferentiation and expansion of MSC intermediates via epithelial
      mesenchymal transition (EMT) may generate beta-cell progenitors. Pancreatic
      epithelial cells from endocrine and non-endocrine tissue were expanded and
      differentiated in a novel pancreatic epithelial expansion medium supplemented
      with growth factors known to support epithelial cell growth (dexamethasone,
      epidermal growth factor, 3,5,3'-triiodo-l-thyronine, bovine brain extract). Cells
      were also infected with a single and dual lentiviral reporter prior to cell
      differentiation. Enhanced green fluorescent protein was controlled by the rat
      Insulin 1 promoter and the monomeric red fluorescent protein was controlled by
      the mouse PDX1 promoter. In combination with lentiviral tracing, cells expanded
      and differentiated in the pancreatic medium were characterized by flow cytometry
      (BD fluorescence activated cell sorting), immunostaining and real-time polymerase
      chain reaction (PCR) (7900HT Fast Realtime PCR System). RESULTS: In the presence
      of 10% serum MSCs rapidly expand in vitro while the epithelial cell population
      declines. The percentage of vimentin(+) cells increased from 22% +/- 5.83% to
      80.43% +/- 3.24% (14 d) and 99.00% +/- 0.0% (21 d), and the percentage of
      epithelial cells decreased from 74.71% +/- 8.34% to 26.57% +/- 9.75% (14 d) and
      4.00% +/- 1.53% (21 d), P < 0.01 for all time points. Our novel pancreatic
      epithelial expansion medium preserved the epithelial cell phenotype and minimized
      epithelial cell dedifferentiation and EMT. Cells expanded in our epithelial
      medium contained significantly less mesenchymal cells (vimentin(+)) compared to
      controls (44.87% +/- 4.93% vs 95.67% +/- 1.36%; P < 0.01). During cell
      differentiation lentiviral reporting demonstrated that, PDX1(+) and insulin(+)
      cells were localized within adherent epithelial cell aggregates compared to
      controls. Compared to starting islets differentiated cells had at least two fold
      higher gene expression of PDX1, insulin, PAX4 and RFX (P < 0.05). CONCLUSION:
      PDX1(+) cells were confined to adherent epithelial cell aggregates and not
      vimentin(+) cells (mesenchymal), suggesting that EMT is not a mechanism for
      generating pancreatic progenitor cells.

PMID- 24567801
TI  - Hepatitis C virus infection and insulin resistance.
AB  - Approximately 170 million people worldwide are chronically infected with
      hepatitis C virus (HCV). Chronic HCV infection is the leading cause for the
      development of liver fibrosis, cirrhosis, hepatocellular carcinoma (HCC) and is
      the primary cause for liver transplantation in the western world. Insulin
      resistance is one of the pathological features in patients with HCV infection and
      often leads to development of type II diabetes. Insulin resistance plays an
      important role in the development of various complications associated with HCV
      infection. Recent evidence indicates that HCV associated insulin resistance may
      result in hepatic fibrosis, steatosis, HCC and resistance to anti-viral
      treatment. Thus, HCV associated insulin resistance is a therapeutic target at any
      stage of HCV infection. HCV modulates normal cellular gene expression and
      interferes with the insulin signaling pathway. Various mechanisms have been
      proposed in regard to HCV mediated insulin resistance, involving up regulation of
      inflammatory cytokines, like tumor necrosis factor-alpha, phosphorylation of
      insulin-receptor substrate-1, Akt, up-regulation of gluconeogenic genes like
      glucose 6 phosphatase, phosphoenolpyruvate carboxykinase 2, and accumulation of
      lipid droplets. In this review, we summarize the available information on how HCV
      infection interferes with insulin signaling pathways resulting in insulin
      resistance. 

PMID- 24567799
TI  - Cardiac autonomic neuropathy in patients with diabetes mellitus.
AB  - Cardiac autonomic neuropathy (CAN) is an often overlooked and common complication
      of diabetes mellitus. CAN is associated with increased cardiovascular morbidity
      and mortality. The pathogenesis of CAN is complex and involves a cascade of
      pathways activated by hyperglycaemia resulting in neuronal ischaemia and cellular
      death. In addition, autoimmune and genetic factors are involved in the
      development of CAN. CAN might be subclinical for several years until the patient
      develops resting tachycardia, exercise intolerance, postural hypotension, cardiac
      dysfunction and diabetic cardiomyopathy. During its sub-clinical phase, heart
      rate variability that is influenced by the balance between parasympathetic and
      sympathetic tones can help in detecting CAN before the disease is symptomatic.
      Newer imaging techniques (such as scintigraphy) have allowed earlier detection of
      CAN in the pre-clinical phase and allowed better assessment of the sympathetic
      nervous system. One of the main difficulties in CAN research is the lack of a
      universally accepted definition of CAN; however, the Toronto Consensus Panel on
      Diabetic Neuropathy has recently issued guidance for the diagnosis and staging of
      CAN, and also proposed screening for CAN in patients with diabetes mellitus. A
      major challenge, however, is the lack of specific treatment to slow the
      progression or prevent the development of CAN. Lifestyle changes, improved
      metabolic control might prevent or slow the progression of CAN. Reversal will
      require combination of these treatments with new targeted therapeutic approaches.
      The aim of this article is to review the latest evidence regarding the
      epidemiology, pathogenesis, manifestations, diagnosis and treatment for CAN. 

PMID- 24567806
TI  - Anesthetic considerations for robotic surgery.
AB  - Recently, demand for minimally invasive surgery has increased greatly. As a
      result, robot-assisted techniques have gained in popularity, because they
      overcome several of the shortcomings of conventional laparoscopic techniques.
      However, robotic surgery may require innovations with regard to patient
      positioning and the overall arrangement of operative equipment and personnel,
      which may go against the conservative nature of anesthesia care.
      Anesthesiologists should become familiar with these changes by learning the basic
      features of robotic surgical systems to offer better anesthetic care and promote
      patient safety. 

PMID- 24567807
TI  - Public awareness about the specialty of anesthesiology and the role of
      anesthesiologists: a national survey.
AB  - BACKGROUND: The aims of this national survey were to determine the views of
      Korean people regarding the specialty of anesthesiology and the role of
      anesthesiologists and to consider the ways in which individual anesthesiologists
      and the Korean Society of Anesthesiologists inform the public. METHODS: This off
      line national survey was conducted by a professional research organization to
      obtain exact and reliable data. The questionnaire included structured questions
      to identify perceptions of the specialty of anesthesiology and the role of
      anesthesiologists inside and outside the operating room, people's desire for
      explanation of anesthesia by anesthesiologists, and their opinion about the best
      way to raise awareness about anesthesia and anesthesiologists. RESULTS: Of the
      respondents, 25.2% did not know that anesthesiologists are in charge of
      anesthesia during surgery. Furthermore, even respondents who knew that had very
      little knowledge of anesthesiologists' actual roles inside and outside the
      operating room. Respondents wanted their anesthesiologist to inform them about
      their anesthesia. CONCLUSIONS: The public's awareness regarding the role of
      anesthesiologists seems to be inadequate. To improve this awareness, in
      hospitals, each anesthesiologist should provide patients with more exact and
      detailed information. Simultaneously, the National Society of Anesthesiology
      should provide systematic information reflecting the public's thoughts.

PMID- 24567808
TI  - A comparison of the clinical duration and recovery characteristics of
      cisatracurium after priming using rocuronium or cisatracurium: preliminary study.
AB  - BACKGROUND: The priming technique can speed up the onset of cisatracurium during
      intubation. However, there have been no reports on the effect of the priming
      technique on duration or recovery profile of cisatracurium. Therefore, we
      attempted to determine whether or not a priming technique with rocuronium or
      cisatracurium can affect clinical duration or recovery profiles of cisatracurium.
      METHODS: A total of 36 patients, ASA I and II, who were scheduled to undergo
      elective surgery, were enrolled. The patients were randomized into three groups
      and administered different drugs for the priming technique. Patients in group 1
      received normal saline (control group). Patients in group 2 received rocuronium
      (0.06 mg/kg), and those in group 3 received cisatracurium (0.01 mg/kg) as a
      priming agent. Three minutes after injection of drugs, intubation doses of
      cisatracurium were administered (Group 1, 0.15 mg/kg; Groups 2 and 3, 0.14
      mg/kg). Anesthesia was induced and maintained with propofol and remifentanil.
      Onset time, clinical duration, recovery index, recovery time, and total recovery
      time were measured by train of four monitoring. RESULTS: Onset time in the group
      2 was significantly shorter than that of group 1 or 3 (P < 0.05). However, no
      significant differences in clinical duration, recovery index, recovery time, and
      total recovery time were observed among the three groups. CONCLUSIONS: Priming
      with rocuronium for 3 minutes resulted in significantly accelerated onset of
      cisatracurium. However, it did not affect the clinical duration and recovery
      profiles of cisatracurium.

PMID- 24567809
TI  - Effect of pretreatment with palonosetron on withdrawal movement associated with
      rocuronium injection.
AB  - BACKGROUND: The main disadvantage of rocuronium is the pain associated with
      vascular injection. We evaluated the efficacy of palonosetron for reducing pain
      after rocuronium injection. METHODS: EIGHTY PATIENTS SCHEDULED FOR ELECTIVE
      SURGERY WERE RANDOMLY DIVIDED INTO TWO GROUPS: Group C (normal saline 1.5 ml, n =
      40) and Group P (palonosetron 0.075 mg, n = 40). Anesthesia was induced with
      thiopental 5 mg/kg and the test drug was injected over 10 seconds. Thirty seconds
      after the injection of the test drug, rocuronium 0.6 mg/kg was injected over 30
      seconds and the response was recorded. Injection pain was graded using a 4-point
      scale. The grade was 0 points for no movement, 1 point for wrist movement, 2
      points for elbow or shoulder movement, and 3 points for whole body movement. Mean
      arterial pressure and heart rate were recorded on arrival in the operating room
      and before and 30 seconds after rocuronim injection. RESULTS: There was no
      significant difference in the grade 1 response between the two groups; however,
      the grade 2 and 3 responses in Group P were 5 (12.5%) and 4 (10%), respectively,
      which were significantly lower than in Group C, with 13 (32.5%) responses for
      each grade. There were no significant differences in hemodynamic changes within
      each group. However, the difference in mean arterial pressure before and after
      the injection of rocuronium was significantly larger in Group C compared to Group
      P. CONCLUSIONS: Pretreatment with palonosetron 0.075 mg reduced the incidence and
      severity of withdrawal movement after rocuronium administration.

PMID- 24567810
TI  - Combined spinal-epidural anesthesia using a reduced-dose of spinal bupivacaine
      and epidural top up leads to faster motor recovery after lower extremity
      surgeries.
AB  - BACKGROUND: The purpose of the present study is to investigate the anesthetic
      effect of reduced doses of spinal bupivacaine with epidural top ups in comparison
      with those of spinal bupivacaine and to determine the adequate doses of drugs
      used during lower extremity surgeries. METHODS: SIXTY ADULT PATIENTS WERE
      RANDOMIZED TO THREE DIFFERENT TECHNIQUE GROUPS: S group (10 mg of spinal
      bupivacaine), SE1 group (7.5 mg of spinal bupivacaine + epidural 1.5% lidocaine
      10 ml) or SE2 group (5 mg of spinal bupivacaine + epidural 1.5% lidocaine 10 ml).
      The level of sensory block, modified Bromage motor scores (MBS), systolic blood
      pressure and heart rate were recorded for 30 min following anesthesia. Peak
      sensory block height and MBS, time for sensory regression to L1 and motor
      recovery to MBS 1, side effects and operator's satisfaction were noted. RESULTS:
      The levels of peak sensory block were similar among the groups (P > 0.05). For
      the SE2 group, the regression to the L1 dermatome was faster (P = 0.004) and the
      maximum MBS was lower (P = 0.001) than that of the other two groups. Motor block
      recovery to MBS 1 was faster for the SE1 and SE2 groups than for the S group (P <
      0.001). The operator's satisfaction scores of the SE2 group were lower than those
      of the other two groups (P = 0.019). CONCLUSIONS: During combined spinal-epidural
      anesthesia, 7.5 mg of spinal bupivacaine and epidural 1.5% lidocaine 10 ml
      produced faster motor recovery than did 10 mg of spinal bupivacaine in patients
      undergoing lower extremity surgeries.

PMID- 24567811
TI  - Comparison of emergence agitation between sevoflurane/nitrous oxide
      administration and sevoflurane administration alone in children undergoing
      adenotonsillectomy with preemptive ketorolac.
AB  - BACKGROUND: Sevoflurane anesthesia commonly causes emergence agitation (EA) in
      children. One previous study has reported that the use of nitrous oxide (N2O)
      during the washout of sevoflurane may reduce EA by decreasing the residual
      sevoflurane concentration, while many animal studies suggest that N2O poses a
      potential risk to children. The present study was designed to compare EA in
      children assigned to receive sevoflurane with N2O (group N) or sevoflurane alone
      (group S). METHODS: We enrolled 80 children aged 3-10 years. Anesthesia was
      induced with 5 mg/kg thiopental sodium, 0.6 mg/kg rocuronium and 0.5 mg/kg
      ketorolac, and was maintained with 50% N2O and sevoflurane in group N or with
      sevoflurane alone in group S. The sevoflurane concentration was adjusted with a
      bispectral index (BIS) of 40-60. After completion of the surgery, N2O and
      sevoflurane were simultaneously discontinued and replaced with oxygen (O2) at 6
      L/min. End-tidal sevoflurane concentration (Et Sevo) (%), BIS at the end of
      surgery, Et Sevo at recovery of self-respiration and emergence profiles were
      recorded. EA occurrence, pain score and rescue fentanyl consumption were assessed
      in the postanesthesia care unit. RESULTS: Et Sevo was significantly lower in
      group N (1.9%) than in group S (2.3%) at the end of surgery. However, there were
      no differences in Et Sevo at recovery of self-respiration, emergence times, the
      incidence of EA, pain score or dose of rescue fentanyl between the groups.
      CONCLUSIONS: In children undergoing adenotonsillectomy with preemptive ketorolac,
      anesthetic maintenance using sevoflurane alone does not affect the incidence of
      EA or emergence profiles compared to anesthetic maintenance using sevoflurane
      with N2O.

PMID- 24567812
TI  - Optimal effect-site concentration of remifentanil when combined with
      dexmedetomidine in patients undergoing cystoscopy.
AB  - BACKGROUND: Cystoscopic procedure is a very common practice in the field of
      urology due to its ability to survey the bladder for a variety of indications.
      However, patients who undergo cystoscopy feel intense pain and discomfort. This
      study investigated the half maximal effective concentration (EC50) of
      remifentanil in preventing cystoscope insertion pain under sedation using
      dexmedetomidine. METHODS: The study was prospectively conducted on 18 male
      patients, aged 18 to 65. Remifentail infusion was initiated together with
      dexmedetomidine, and started at a dose of 2.4 ng/ml on the first patient. The
      effect-site concentration (Ce) of remifentanil for each subsequent patient was
      determined by the previous patient's response using Dixon's up-and-down method
      with an interval of 0.3 ng/ml. Patients received a loading dose of 1.0 ug/kg
      dexmedetomidine over 10 minutes, followed by a maintenance dose of 0.6 ug/kg/hr.
      After the patient's OAA/S score (Observer's Assessment of Alertness/Sedation
      scale) reached 3-4, and the Ce of remifentanil reached target concentration, the
      urologist was allowed to insert the cystoscope and the pain responses were
      observed. RESULTS: The effect-site concentration of remifentanil required to
      prevent cystoscope insertion pain in 50% of patients under sedation using
      dexmedetomidine was 1.30 +/- 0.12 ng/ml by Dixon's up-and-down method. The
      logistic regression curve of the probability of response showed that the EC50 and
      EC95 values (95% confidence limits) of remifentanil were 1.33 ng/ml (1.12-1.52
      ng/ml) and 1.58 ng/ml (1.44-2.48 ng/ml), respectively. CONCLUSIONS: Cystoscopic
      procedure can be carried out successfully without any pain or adverse effects by
      optimal remifentanil effect-site concentration (EC50, 1.33 ng/ml; EC95, 1.58 ng/
      ml) combined with sedation using dexmedetomidine.

PMID- 24567813
TI  - Interaction between postoperative shivering and hyperalgesia caused by high-dose
      remifentanil.
AB  - BACKGROUND: High-dose remifentanil-based anesthesia is associated with opioid
      induced hyperalgesia (OIH) and postanesthetic shivering (PAS). These effects can
      be prevented by N-methyl-d-aspartate (NMDA) receptor antagonists. This study
      aimed to investigate correlations between OIH and PAS caused by high-dose
      remifentanil and the effects of low-dose ketamine on OIH and PAS. METHODS:
      Seventy-five patients scheduled for single-port laparoscopic gynecologic surgery
      were randomly allocated into three groups, each of which received intraoperative
      remifentanil: group L at 0.1 ug/kg/min; group H at 0.3 ug/kg/min; and group HK at
      0.3 ug/kg/min plus 0.25 mg/kg ketamine just before incision, followed by a
      continuous infusion of 5 ug/kg/min ketamine until skin closure. RESULTS: PAS,
      postoperative tactile pain threshold, and the extent of hyperalgesia in group H
      were significantly different (P < 0.05) than in the other two groups. PAS was
      significantly correlated with OIH, including mechanically evoked pain such as
      postoperative tactile pain threshold (r = -0.529, P = 0.01) (r = -0.458, P =
      0.021) and the extent of hyperalgesia (r = 0.537, P = 0.002) (r = 0.384, P =
      0.031), respectively, in group H and group HK. Notably, both groups were treated
      with high-dose remifentanil. Tympanic membrane temperature, time to first
      postoperative analgesic requirement, postoperative pain scores, analgesic
      consumption, and cumulative patient-controlled analgesia volume containing
      morphine were comparable in all three groups. CONCLUSIONS: OIH, including the
      enhanced perception of pain, and PAS were both associated with high-dose
      remifentanil, were significantly correlated and were attenuated by a low dose of
      ketamine. This suggests that a common mechanism in part mediated through
      activation of the central glutamatergic system (e.g., NMDA receptors), underlies
      the two effects caused by high doses of remifentanil.

PMID- 24567814
TI  - Ketamine reduces the induced spinal p38 MAPK and pro-inflammatory cytokines in a
      neuropathic rats.
AB  - BACKGROUND: Neuropathic rats created by spinal nerve ligation are known to show
      higher levels of p38, c-Jun NH2-terminal kinase, and extracellular signal
      regulated kinase p44/42 (ERK 1/2) of the mitogen-activated protein kinases
      (MAPKs). The authors of this study aimed to understand the effect of ketamine on
      p38 MAPK and inflammatory responses, as well as its effect on the development of
      neuropathic pain. METHODS: The neuropathic rats were prepared by Chung's method
      with Sprague-Dawley rats. The research was carried out on three groups, a sham
      operated group, a neuropathic pain and normal saline (NP + NS) group, and a
      neuropathic pain and ketamine (NP + Keta) group. The normal saline or ketamine
      was infused into the neuropathic rats through a mini-osmotic pump implanted in
      the subcutaneous space. After a week, the quantities of phospho-p38, p38 MAPK and
      pro-inflammatory cytokines were measured and compared through western blots and
      reverse transcriptase-polymerase chain reaction. RESULTS: In comparison to the
      control group, the NP + NS group showed a significant increase of phospho-p38 and
      p38 MAPK, as well as of the proinflammatory cytokines, tumor necrosis factor
      alpha (TNFalpha), and intercellular adhesion molecule 1 (ICAM1). However, in the
      NP + Keta group, phospho-p38, p38 MAPK and TNFalpha and, ICAM1 were reduced in
      comparison to the NP + NS group. The paw withdrawal threshold test also showed
      the trend of recovery from the mechanical allodynia in the NP + Keta group.
      CONCLUSIONS: In the development of neuropathic pain, p38 MAPK and inflammatory
      responses are significantly related, and the use of ketamine reduces p38 MAPK and
      proinflammatory cytokines. Thus, the adequate use of ketamine could be effective
      for the prevention and treatment of neuropathic pain following peripheral injury.

PMID- 24567815
TI  - Endobronchial hemorrhage after intubation with double-lumen endotracheal tube in
      a patient with idiopathic thrombocytopenic purpura for minimally invasive cardiac
      surgery: a case report.
AB  - Minimally invasive cardiac surgery (MICS) requires lung isolation. Lung isolation
      is usually achieved with double-lumen endotracheal tube (DLT). Patients with
      idiopathic thrombocytopenic purpura (ITP) have an increased risk of bleeding
      events. We suspected endobronchial hemorrhage after exchange of DLT during
      induction of anesthesia for replacement of mitral valve in a 62-year-old man with
      a known ITP. The MICS was stopped and bronchial artery embolization was performed
      in the angiographic room. In the present case, in order to reduce the risk of
      bronchial arterial injury in ITP patient we intubated with single lumen
      endotracheal tube. Lung isolation led to achievement of intermittent total lung
      deflation. Based on the results, we recommend a high-dose intravenous
      immunoglobulin therapy and platelet transfusion prior to cardiac surgery in
      patients with ITP to increase platelet count. Moreover, it is proposed that in
      order to clear the vision during the operation, ventilation can be held or made
      intermittent both prior to cardiopulmonary bypass or at its conclusion to permit
      exposure. 

PMID- 24567816
TI  - The effect of ketamine as an additive in epidural block on the intractable
      herpetic neuralgia: a case report.
AB  - Ketamine has been shown to have analgesic effect by blocking N-methyl-D-aspartate
      receptor, thus preventing and reducing central sensitization caused by peripheral
      nociceptive stimulation. However, due to lack of knowledge about its safety and
      toxicity in the central nervous system, either epidural or intrathecal injection
      of ketamine still remains controversial. Here, we describe a case report of
      satisfactory pain relief after the addition of ketamine in epidural injection in
      a patient with severe herpes zoster pain that was refractory to conventional
      medication, intravenous opioids and continuous epidural block. This case
      indicates the viability of epidural ketamine injection in patients with
      intractable herpetic neuralgia. 

PMID- 24567817
TI  - The anesthetic experience of implantable left ventricular assist device
      insertion: a case report.
AB  - Because of insufficient number of donor hearts for cardiac transplantation, the
      use of implantable left ventricular assist device (LVAD) has been increasing as
      an alternative. During this procedure, the fundamental role of anesthesiologists
      would be to maintain stable hemodynamics. This report describes the anesthetic
      case of a 75-year-old man who underwent implantable LVAD placement as a
      destination therapy of his heart failure in Korea. The procedure and anesthesia
      were uneventful with transesophageal echocariographic guide. He moved to the ward
      on postoperative day 10 without fatal complication. 

PMID- 24567818
TI  - Isolated central venous pressure elevation caused by hematoma formation
      compressing the superior vena cava following a Bentall operation: a case report.
AB  - We present a case of a patient exhibiting isolated elevation of the central
      venous pressure with minimal hemodynamic deterioration in an immediate
      postoperative period after Bentall operation requiring re-exploration. Isolated
      elevation of the central venous pressure usually alerts physicians of a volume
      overload or right ventricular dysfunction. However, even in the absence of
      significant hemodynamic deterioration, the development of loculated hematoma that
      compresses the superior vena cava should be ruled out, as it can be life
      threatening through the formation of cerebral and laryngeal edema, similar to
      superior vena cava syndrome. This case emphasizes the importance of a prompt
      differential diagnosis of the isolated central venous pressure elevation after
      cardiac surgery with transesophageal echocardiography for the administration of
      appropriate treatment. 

PMID- 24567819
TI  - Usefulness of intraoperative real-time three-dimensional transesophageal
      echocardiography for pre-procedural evaluation of mitral valve cleft: a case
      report.
AB  - A precise pre-procedural evaluation of mitral valve (MV) pathology is essential
      for planning the surgical strategy for severe mitral regurgitation (MR) and
      preparing for the intraoperative procedure. In the present case, a 38-year-old
      woman was scheduled to undergo MV replacement due to severe MR. She had a history
      of undergoing percutaneous balloon valvuloplasty due to rheumatic mitral stenosis
      during a previous pregnancy. A preoperative transthoracic echocardiography
      suggested a tear in the mid tip of the anterior mitral leaflet. However, the "en
      face" view of the MV in the left atrial perspective using intraoperative real
      time three-dimensional transesophageal echocardiography (RT 3D-TEE) provided a
      different diagnosis: a torn cleft in the P2-scallop of the posterior mitral
      leaflet (PML) with rupture of the chordae. Thus, surgical planning was changed
      intraoperatively to MV repair (MVRep) consisting of patch closure of the PML,
      commissurotomy, and lifting annuloplasty. The present case shows that
      intraoperative RT 3D-TEE provides more precise and reliable spatial information
      of MV for MVRep and facilitates critical surgical decision-making. 

PMID- 24567820
TI  - Torsade de pointes in liver transplantation recipient after induction of general
      anesthesia: a case report.
AB  - Torsade de pointes (TdP) is an uncommon and specific form of polymorphic
      ventricular tachycardia, associated with a prolonged QT interval. Prolongation of
      the QT interval is the most widely recognized electrophysiological abnormality in
      patients with liver cirrhosis. We observed a case of TdP leading to
      cardiopulmonary resuscitation after the induction of general anesthesia, in a
      patient with liver cirrhosis scheduled for emergency cadaveric donor liver
      transplantation. The patient had mild QT prolongation on preoperative
      electrocardiography with a corrected QT (QTc) interval of 455 ms. Drugs used in
      the preoperative period can elongate cardiac repolarization. Sevoflurane and 5
      hydroxytryptamine type 3 receptor antagonists such as palonsetron, used during
      general anesthesia may have triggered further QT prolongation, producing a fatal
      condition such as TdP. More caution and consideration in selecting drugs for
      anesthetic management are necessary for liver cirrhosis patients, especially in
      patients with preoperative QT prolongation. 

PMID- 24567822
TI  - Environmental effects on molecular and phenotypic variation in populations of
      Eruca sativa across a steep climatic gradient.
AB  - In Israel Eruca sativa has a geographically narrow distribution across a steep
      climatic gradient that ranges from mesic Mediterranean to hot desert
      environments. These conditions offer an opportunity to study the influence of the
      environment on intraspecific genetic variation. For this, we combined an analysis
      of neutral genetic markers with a phenotypic evaluation in common-garden
      experiments, and environmental characterization of populations that included
      climatic and edaphic parameters, as well as geographic distribution. A Bayesian
      clustering of individuals from nine representative populations based on amplified
      fragment length polymorphism (AFLP) divided the populations into a southern and a
      northern geographic cluster, with one admixed population at the geographic border
      between them. Linear mixed models, with cluster added as a grouping factor,
      revealed no clear effects of environment or geography on genetic distances, but
      this may be due to a strong association of geography and environment with genetic
      clusters. However, environmental factors accounted for part of the phenotypic
      variation observed in the common-garden experiments. In addition, candidate loci
      for selection were identified by association with environmental parameters and by
      two outlier methods. One locus, identified by all three methods, also showed an
      association with trichome density and herbivore damage, in net-house and field
      experiments, respectively. Accordingly, we propose that because trichomes are
      directly linked to defense against both herbivores and excess radiation, they
      could potentially be related to adaptive variation in these populations. These
      results demonstrate the value of combining environmental and phenotypic data with
      a detailed genetic survey when studying adaptation in plant populations. This
      article describes the use of several types of data to estimate the influence of
      the environment on intraspecific genetic variation in populations originating
      from a steep climatic gradient. In addition to molecular marker data, we made use
      of phenotypic evaluation from common garden experiments, and a broad GIS based
      environmental data with edaphic information gathered in the field. This study,
      among others, lead to the identification of an outlier locus with an association
      to trichome formation and herbivore defense, and its ecological adaptive value is
      discussed. 

PMID- 24567821
TI  - Frequency of hybridization between Ostrinia nubilalis E-and Z-pheromone races in
      regions of sympatry within the United States.
AB  - Female European corn borer, Ostrinia nubilalis, produce and males respond to sex
      pheromone blends with either E- or Z-Delta11-tetradecenyl acetate as the major
      component. E- and Z-race populations are sympatric in the Eastern United States,
      Southeastern Canada, and the Mediterranean region of Europe. The E- and Z
      pheromone races of O. nubilalis are models for incipient species formation, but
      hybridization frequencies within natural populations remain obscure due to lack
      of a high-throughput phenotyping method. Lassance et al. previously identified a
      pheromone gland-expressed fatty-acyl reductase gene (pgfar) that controls the
      ratio of Delta11-tetradecenyl acetate stereoisomers. We identified three single
      nucleotide polymorphism (SNP) markers within pgfar that are differentially fixed
      between E- and Z-race females, and that are >=98.2% correlated with female
      pheromone ratios measured by gas chromatography. Genotypic data from locations in
      the United States demonstrated that pgfar-z alleles were fixed within
      historically allopatric Z-pheromone race populations in the Midwest, and that
      hybrid frequency ranged from 0.00 to 0.42 within 11 sympatric sites where the two
      races co-occur in the Eastern United States (mean hybridization frequency or
      heterozygosity (H O) = 0.226 +/- 0.279). Estimates of hybridization between the E
      and Z-races are important for understanding the dynamics involved in maintaining
      race integrity, and are consistent with previous estimates of low levels of
      genetic divergence between E- and Z-races and the presence of weak prezygotic
      mating barriers. This work describes the development of new single nucleotide
      polymorphism (SNP) markers within the pheromone gland expressed fatty acyl
      reductase (pgfar) gene of Ostrinia nubilalis. These SNPs were shown to segregate
      based upon female pheromone production, and thus provide the first description of
      an assay for genetic determination of O. nubilalis pheromone strain from field
      collected samples. These assays were applied to estimate hybridization within
      field populations, and represent valuable tools for future population genetic
      studies of this species. 

PMID- 24567823
TI  - Populations at risk: conservation genetics of kangaroo mice (Microdipodops) of
      the Great Basin Desert.
AB  - The Great Basin Desert of western North America has experienced frequent habitat
      alterations due to a complex biogeographic history and recent anthropogenic
      impacts, with the more recent alterations likely resulting in the decline of
      native fauna and flora. Dark (Microdipodops megacephalus) and pallid (M.
      pallidus) kangaroo mice are ecological specialists found within the Great Basin
      Desert and are potentially ideal organisms for assessing ecosystem health and
      inferring the biogeographic history of this vulnerable region. Herein, newly
      acquired nuclear-encoded microsatellite loci were utilized to assess patterns of
      variation within and among spatially discrete groups of kangaroo mice and to
      evaluate gene flow, demographic trends, and genetic integrity. Results confirm
      that there are at least three genetically distinct units within M. megacephalus
      and two such units within M. pallidus. The three units of M. megacephalus appear
      to have different demographic histories, with effectively no gene flow among them
      since their divergence. Similarly, the two units of M. pallidus also appear to
      have experienced different demographic histories, with effectively no gene
      exchange. Contemporary effective population sizes of all groups within
      Microdipodops appear to be low (<500), suggesting that each genetic lineage may
      have difficulty coping with changing environmental pressures and hence may be at
      risk of extirpation. Results of this study indicate that each Microdipodops group
      should be recognized, and therefore managed, as a separate unit in an effort to
      conserve these highly specialized taxa that contribute to the diversity of the
      Great Basin Desert ecosystem. The Great Basin Desert of western North America has
      experienced frequent habitat alterations due to a complex biogeographic history
      and recent anthropogenic impacts, with the more recent alterations likely
      resulting in the decline of native fauna and flora. Herein, newly acquired
      nuclear-encoded microsatellite loci were utilized to assess patterns of variation
      within and among spatially discrete groups of the dark (Microdipodops
      megacephalus) and pallid (M. pallidus) kangaroo mouse, and to evaluate gene flow,
      demographic trends, and genetic integrity. Results of this study indicate that
      each Microdipodops group should be recognized, and therefore managed, as a
      separate unit in an effort to conserve these highly specialized taxa that
      contribute to the diversity of the Great Basin Desert ecosystem (photo credit J.
      C. Hafner). 

PMID- 24567824
TI  - Experimental demonstration of a parasite-induced immune response in wild birds:
      Darwin's finches and introduced nest flies.
AB  - Ecological immunology aims to explain variation among hosts in the strength and
      efficacy of immunological defenses. However, a shortcoming has been the failure
      to link host immune responses to actual parasites under natural conditions. Here,
      we present one of the first experimental demonstrations of a parasite-induced
      immune response in a wild bird population. The recently introduced ectoparasitic
      nest fly Philornis downsi severely impacts the fitness of Darwin's finches and
      other land birds in the Galapagos Islands. An earlier study showed that female
      medium ground finches (Geospiza fortis) had P. downsi-binding antibodies
      correlating with presumed variation in fly exposure over time. In the current
      study, we experimentally manipulated fly abundance to test whether the fly does,
      in fact, cause changes in antibody levels. We manipulated P. downsi abundance in
      nests and quantified P. downsi-binding antibody levels of medium ground finch
      mothers, fathers, and nestlings. We also quantified host behaviors, such as
      preening, which can integrate with antibody-mediated defenses against
      ectoparasites. Philornis downsi-binding antibody levels were significantly higher
      among mothers at parasitized nests, compared to mothers at (fumigated)
      nonparasitized nests. Mothers with higher antibody levels tended to have fewer
      parasites in their nests, suggesting that antibodies play a role in defense
      against parasites. Mothers showed no behavioral changes that would enhance the
      effectiveness of the immune response. Neither adult males, nor nestlings, had P.
      downsi-induced immunological or behavioral responses that would enhance defense
      against flies. None of the parasitized nests fledged any offspring, despite the
      immune response by mothers. Thus, this study shows that, while the immune
      response of mothers appeared to be defensive, it was not sufficient to rescue
      current reproductive fitness. This study further shows the importance of testing
      the fitness consequences of immune defenses, rather than assuming that such
      responses increase host fitness. Host immune responses can protect against the
      negative fitness consequences of parasitism; however, the strength and
      effectiveness of these responses vary among hosts. Strong host immune responses
      are often assumed to correlate with greater host fitness. This study investigates
      the relationship between host immune response, parasite load, and host fitness
      using Darwin's finches and an invasive nest parasite. We found that while the
      immune response of mothers appeared defensive, it did not rescue current
      reproductive fitness. 

PMID- 24567826
TI  - Snow cover and extreme winter warming events control flower abundance of some,
      but not all species in high arctic Svalbard.
AB  - The High Arctic winter is expected to be altered through ongoing and future
      climate change. Winter precipitation and snow depth are projected to increase and
      melt out dates change accordingly. Also, snow cover and depth will play an
      important role in protecting plant canopy from increasingly more frequent extreme
      winter warming events. Flower production of many Arctic plants is dependent on
      melt out timing, since season length determines resource availability for flower
      preformation. We erected snow fences to increase snow depth and shorten growing
      season, and counted flowers of six species over 5 years, during which we
      experienced two extreme winter warming events. Most species were resistant to
      snow cover increase, but two species reduced flower abundance due to shortened
      growing seasons. Cassiope tetragona responded strongly with fewer flowers in deep
      snow regimes during years without extreme events, while Stellaria crassipes
      responded partly. Snow pack thickness determined whether winter warming events
      had an effect on flower abundance of some species. Warming events clearly reduced
      flower abundance in shallow but not in deep snow regimes of Cassiope tetragona,
      but only marginally for Dryas octopetala. However, the affected species were
      resilient and individuals did not experience any long term effects. In the case
      of short or cold summers, a subset of species suffered reduced reproductive
      success, which may affect future plant composition through possible cascading
      competition effects. Extreme winter warming events were shown to expose the
      canopy to cold winter air. The following summer most of the overwintering flower
      buds could not produce flowers. Thus reproductive success is reduced if this
      occurs in subsequent years. We conclude that snow depth influences flower
      abundance by altering season length and by protecting or exposing flower buds to
      cold winter air, but most species studied are resistant to changes. Winter
      warming events, often occurring together with rain, can substantially remove snow
      cover and thereby expose plants to cold winter air. Depending on morphology,
      different parts of the plant can be directly exposed. On this picture, we see
      Dryas octopetala seed heads from the previous growing season protrude through the
      remaining ice layer after a warming event in early 2010. The rest of the plant,
      including meristems and flower primordia, are still somewhat protected by the
      ice. In the background we can see a patch of Cassiope tetragona protruding
      through the ice; in this case, the whole plant including flower primordia is
      exposed, which might be one reason why this species experienced a loss of flowers
      the following season. Photograph by Philipp Semenchuk. 

PMID- 24567825
TI  - Combining molecular evolution and environmental genomics to unravel adaptive
      processes of MHC class IIB diversity in European minnows (Phoxinus phoxinus).
AB  - Host-pathogen interactions are a major evolutionary force promoting local
      adaptation. Genes of the major histocompatibility complex (MHC) represent unique
      candidates to investigate evolutionary processes driving local adaptation to
      parasite communities. The present study aimed at identifying the relative roles
      of neutral and adaptive processes driving the evolution of MHC class IIB (MHCIIB)
      genes in natural populations of European minnows (Phoxinus phoxinus). To this
      end, we isolated and genotyped exon 2 of two MHCIIB gene duplicates (DAB1 and
      DAB3) and 1'665 amplified fragment length polymorphism (AFLP) markers in nine
      populations, and characterized local bacterial communities by 16S rDNA barcoding
      using 454 amplicon sequencing. Both MHCIIB loci exhibited signs of historical
      balancing selection. Whereas genetic differentiation exceeded that of neutral
      markers at both loci, the populations' genetic diversities were positively
      correlated with local pathogen diversities only at DAB3. Overall, our results
      suggest pathogen-mediated local adaptation in European minnows at both MHCIIB
      loci. While at DAB1 selection appears to favor different alleles among
      populations, this is only partially the case in DAB3, which appears to be locally
      adapted to pathogen communities in terms of genetic diversity. These results
      provide new insights into the importance of host-pathogen interactions in driving
      local adaptation in the European minnow, and highlight that the importance of
      adaptive processes driving MHCIIB gene evolution may differ among duplicates
      within species, presumably as a consequence of alternative selective regimes or
      different genomic context. Using next-generation sequencing, the present
      manuscript identifies the relative roles of neutral and adaptive processes
      driving the evolution of MHC class IIB (MHCIIB) genes in natural populations of a
      cyprinid fish: the European minnow (Phoxinus phoxinus). We highlight that the
      relative importance of neutral versus adaptive processes in shaping immune
      competence may differ between duplicates as a consequence of alternative
      selective regimes or different genomic contexts. 

PMID- 24567827
TI  - High-throughput SNP-genotyping analysis of the relationships among Ponto-Caspian
      sturgeon species.
AB  - Legally certified sturgeon fisheries require population protection and
      conservation methods, including DNA tests to identify the source of valuable
      sturgeon roe. However, the available genetic data are insufficient to distinguish
      between different sturgeon populations, and are even unable to distinguish
      between some species. We performed high-throughput single-nucleotide polymorphism
      (SNP)-genotyping analysis on different populations of Russian (Acipenser
      gueldenstaedtii), Persian (A. persicus), and Siberian (A. baerii) sturgeon
      species from the Caspian Sea region (Volga and Ural Rivers), the Azov Sea, and
      two Siberian rivers. We found that Russian sturgeons from the Volga and Ural
      Rivers were essentially indistinguishable, but they differed from Russian
      sturgeons in the Azov Sea, and from Persian and Siberian sturgeons. We identified
      eight SNPs that were sufficient to distinguish these sturgeon populations with
      80% confidence, and allowed the development of markers to distinguish sturgeon
      species. Finally, on the basis of our SNP data, we propose that the A. baerii
      like mitochondrial DNA found in some Russian sturgeons from the Caspian Sea arose
      via an introgression event during the Pleistocene glaciation. In the present
      study, the high-throughput genotyping analysis of several sturgeon populations
      was performed. SNP markers for species identification were defined. The possible
      explanation of the baerii-like mitotype presence in some Russian sturgeons in the
      Caspian Sea was suggested. 

PMID- 24567828
TI  - Noncrop flowering plants restore top-down herbivore control in agricultural
      fields.
AB  - Herbivore populations are regulated by bottom-up control through food
      availability and quality and by top-down control through natural enemies.
      Intensive agricultural monocultures provide abundant food to specialized
      herbivores and at the same time negatively impact natural enemies because
      monocultures are depauperate in carbohydrate food sources required by many
      natural enemies. As a consequence, herbivores are released from both types of
      control. Diversifying intensive cropping systems with flowering plants that
      provide nutritional resources to natural enemies may enhance top-down control and
      contribute to natural herbivore regulation. We analyzed how noncrop flowering
      plants planted as "companion plants" inside cabbage (Brassica oleracea) fields
      and as margins along the fields affect the plant-herbivore-parasitoid-predator
      food web. We combined molecular analyses quantifying parasitism of herbivore eggs
      and larvae with molecular predator gut content analysis and a comprehensive
      predator community assessment. Planting cornflowers (Centaurea cynanus), which
      have been shown to attract and selectively benefit Microplitis mediator, a larval
      parasitoid of the cabbage moth Mamestra brassicae, between the cabbage heads
      shifted the balance between trophic levels. Companion plants significantly
      increased parasitism of herbivores by larval parasitoids and predation on
      herbivore eggs. They furthermore significantly affected predator species
      richness. These effects were present despite the different treatments being close
      relative to the parasitoids' mobility. These findings demonstrate that habitat
      manipulation can restore top-down herbivore control in intensive crops if the
      right resources are added. This is important because increased natural control
      reduces the need for pesticide input in intensive agricultural settings, with
      cascading positive effects on general biodiversity and the environment. Companion
      plants thus increase biodiversity both directly, by introducing new habitats and
      resources for other species, and indirectly by reducing mortality of nontarget
      species due to pesticides. This study provides a comprehensive assessment of how
      habitat manipulation affects biocontrol services of a natural enemy community
      including both parasitoids and generalist predators. The trophic interactions
      between pests, parasitoids and predators were determined to achieve a better
      systemic understanding of top-down herbivore control, which can be strengthened
      when natural enemies complement each other or dampened by intraguild
      interactions. Our approach to selectively enhance the third trophic level to
      counteract specific herbivores was successful for both predators and parasitoids.
      Our results show significant positive effects of companion plants on predation of
      pest eggs and parasitism of pest larvae. Importantly, our data also suggest that
      carabids, staphylinids and spiders do not substantially interfere with parasitoid
      biocontrol as parasitoid DNA was rarely detected in predator guts. 

PMID- 24567829
TI  - Investigating sex-specific dynamics using uniparental markers: West New Guinea as
      a case study.
AB  - Mitochondrial DNA (mtDNA) and Y chromosome (NRY) genetic markers have been often
      contrasted to investigate sex-specific dynamics. Traditionally, isolation by
      distance, intrapopulation genetic diversity and population differentiation are
      estimated from both markers and compared. Two possible sources of bias are often
      neglected. First, kilometric distances are frequently used as predictor of the
      connectivity between groups, hiding the role played by environmental features at
      a microgeographic scale. Second, the comparison of intrapopulation diversity and
      population differentiation between mtDNA and NRY is hampered by their different
      mutational mechanisms and rates. Here, we show how to account for these biases by
      analyzing from a different perspective a published dataset of eight West New
      Guinea (WNG) populations for which mtDNA control region sequences and seven
      linked NRY microsatellites had been typed. First, we modeled the connectivity
      among sampled populations by computing the number of days required to travel
      between groups. Then, we investigated the differences between the two sexes
      accounting for the molecular characteristics of the markers examined to obtain
      estimates on the product of the effective population size and the migration rate
      among demes (Nm). We achieved this goal by studying the shape of the gene
      genealogy at several sampling levels and using spatial explicit simulations. Both
      the direction and the rate of migration differ between male and females, with an
      Nm estimated to be >6 times higher in the latter under many evolutionary
      scenarios. We finally highlight the importance of applying metapopulation models
      when analyzing the genetic diversity of a species. We have applied the prediction
      of the sampling theory in a meta-population and we have corroborated our finding
      using spatial explicit simulations. Both approaches are fundamentally meant to
      deal with structured populations: we strongly believe in the importance of
      tacking structure into account when inferring the demographic history of a
      species. 

PMID- 24567830
TI  - Male-male aggression peaks at intermediate relatedness in a social spider mite.
AB  - Theory predicts that when individuals live in groups or colonies, male-male
      aggression peaks at intermediate levels of local average relatedness. Assuming
      that aggression is costly and directed toward nonrelatives and that competition
      for reproduction acts within the colony, benefits of aggressive behavior are
      maximized in colonies with a mix of related and unrelated competitors because
      aggression hurts nonkin often, thereby favoring reproduction of kin. This leads
      to a dome-shaped relation between male-male aggression and average relatedness.
      This prediction has been tested with bacteria in the laboratory, but not with
      organisms in the field. We study how male-male aggression varies with relatedness
      in the social spider mite Stigmaeopsis miscanthi. We sampled 25 populations
      across a wide geographic range between Taiwan and Japan, representing a gradient
      of high to low within-population relatedness. For each population the weaponry of
      males was measured as the length of the first pair of legs, and male-male
      aggression was tested by placing pairs of nonsibling males together and scoring
      the frequency of male death over a given period. As these two morphological and
      behavioral variables correlate strongly, they both reflect the intensity of male
      male conflict. Our data on the social spider mite show that male-male aggression
      as well as weapon size strongly peak at intermediate, average relatedness,
      thereby confirming theoretical predictions. Inclusive fitness theory predicts
      that when individuals live in groups or colonies, aggression should peak at
      intermediate levels of average relatedness in the colony. Here, we study how male
      male aggression varies with average relatedness in naturally occurring colonies
      of the social spider mite Stigmaeopsis miscanthi. In support of theory, male-male
      aggression and weapon size strongly peak at intermediate average relatedness. 

PMID- 24567831
TI  - Phylogenetic and morphometric analyses reveal ecophenotypic plasticity in
      freshwater mussels Obovaria jacksoniana and Villosa arkansasensis (Bivalvia:
      Unionidae).
AB  - Freshwater mollusk shell morphology exhibits clinal variation along a stream
      continuum that has been termed the Law of Stream Distribution. We analyzed
      phylogenetic relationships and morphological similarity of two freshwater mussels
      (Bivalvia: Unionidae), Obovaria jacksoniana and Villosa arkansasensis, throughout
      their ranges. The objectives were to investigate phylogenetic structure and
      evolutionary divergence of O. jacksoniana and V. arkansasensis and morphological
      similarity between the two species. Our analyses were the first explicit tests of
      phenotypic plasticity in shell morphologies using a combination of genetics and
      morphometrics. We conducted phylogenetic analyses of mitochondrial DNA (1416 bp;
      two genes) and morphometric analyses for 135 individuals of O. jacksoniana and V.
      arkansasensis from 12 streams. We examined correlations among genetic,
      morphological, and spatial distances using Mantel tests. Molecular phylogenetic
      analyses revealed a monophyletic relationship between O. jacksoniana and V.
      arkansasensis. Within this O. jacksoniana/V. arkansasensis complex, five distinct
      clades corresponding to drainage patterns showed high genetic divergence.
      Morphometric analysis revealed relative differences in shell morphologies between
      the two currently recognized species. We conclude that morphological differences
      between the two species are caused by ecophenotypic plasticity. A series of
      Mantel tests showed regional and local genetic isolation by distance. We observed
      clear positive correlations between morphological and geographic distances within
      a single drainage. We did not observe correlations between genetic and
      morphological distances. Phylogenetic analyses suggest O. jacksoniana and V.
      arkansasensis are synonomous and most closely related to a clade composed of O.
      retusa, O. subrotunda, and O. unicolor. Therefore, the synonomous O. jacksoniana
      and V. arkansasensis should be recognized as Obovaria arkansasensis (Lea 1862) n.
      comb. Phylogenetic analyses also showed relative genetic isolation among
      drainages, suggesting no current gene flow. Further investigation of in-progress
      speciation and/or cryptic species within O. arkansasensis is warranted followed
      by appropriate revision of conservation management designations. In this study,
      we found Obovaria jacksoniana and Villosa arkansasensis are synonomous. We
      suggest that morphological differences between the two species are caused by
      ecophenotypic plasticity, where V. arkansasensis is the upstream morphotype and
      O. jacksoniana is the downstream morphotype of a single species. 

PMID- 24567832
TI  - Comparing food limitation among three stages of nesting: supplementation
      experiments with the burrowing owl.
AB  - Food availability is an important limiting factor for avian reproduction. In
      altricial birds, food limitation is assumed to be more severe during the nestling
      stage than during laying or incubation, but this has yet to be adequately tested.
      Using food-supplementation experiments over a 5-year period, we determined the
      degree and timing of food limitation for burrowing owls (Athene cunicularia)
      breeding in Canada. Burrowing owls are an endangered species and food limitation
      during the nestling stage could influence reproductive performance of this
      species at the northern extent of their range. Supplemented pairs fledged on
      average 47% more owlets than unfed pairs, except during a year when natural food
      was not limiting (i.e., a prey irruption year). The difference in fledgling
      production resulted from high nestling mortality in unfed broods, with 96% of all
      nestling deaths being attributed to food shortage. Supplemental feeding during
      the nestling period also increased fledgling structural size. Pairs fed from the
      start of laying produced the same number of hatchlings as pairs that received no
      supplemental food before hatch. Furthermore, pairs supplemented from egg laying
      to fledging and pairs supplemented during the nestling period alone had the same
      patterns of nestling survival, equal numbers of fledglings, and similar fledgling
      mass and structural size. Our results provide empirical support for the
      hypothesis that the nestling period is the most food-limited phase of the
      breeding cycle. The experimental design we introduce here could be used with
      other altricial species to examine how the timing of food limitation differs
      among birds with a variety of life-history strategies. For burrowing owls, and
      other species with similar life histories, long-term, large-scale, and
      appropriately timed habitat management increasing prey abundance or availability
      is critical for conservation. Our results provide empirical support for the
      hypothesis that the nestling period is the most food-limited phase of the
      breeding cycle. For burrowing owls, and other species with similar life
      histories, long-term, large-scale, and appropriately timed habitat management
      increasing prey abundance or availability is critical for conservation. 

PMID- 24567834
TI  - Global change-type drought-induced tree mortality: vapor pressure deficit is more
      important than temperature per se in causing decline in tree health.
AB  - Drought-induced tree mortality is occurring across all forested continents and is
      expected to increase worldwide during the coming century. Regional-scale forest
      die-off influences terrestrial albedo, carbon and water budgets, and land-surface
      energy partitioning. Although increased temperatures during drought are widely
      identified as a critical contributor to exacerbated tree mortality associated
      with "global-change-type drought", corresponding changes in vapor pressure
      deficit (D) have rarely been considered explicitly and have not been
      disaggregated from that of temperature per se. Here, we apply a detailed
      mechanistic soil-plant-atmosphere model to examine the impacts of drought,
      increased air temperature (+2 degrees C or +5 degrees C), and increased vapor
      pressure deficit (D; +1 kPa or +2.5 kPa), singly and in combination, on net
      primary productivity (NPP) and transpiration and forest responses, especially
      soil moisture content, leaf water potential, and stomatal conductance. We show
      that increased D exerts a larger detrimental effect on transpiration and NPP,
      than increased temperature alone, with or without the imposition of a 3-month
      drought. Combined with drought, the effect of increased D on NPP was
      substantially larger than that of drought plus increased temperature. Thus, the
      number of days when NPP was zero across the 2-year simulation was 13 or 14 days
      in the control and increased temperature scenarios, but increased to
      approximately 200 days when D was increased. Drought alone increased the number
      of days of zero NPP to 88, but drought plus increased temperature did not
      increase the number of days. In contrast, drought and increased D resulted in the
      number of days when NPP = 0 increasing to 235 (+1 kPa) or 304 days (+2.5 kPa). We
      conclude that correct identification of the causes of global change-type
      mortality events requires explicit consideration of the influence of D as well as
      its interaction with drought and temperature. This study disaggregates the
      influence of temperature and vapour pressure deficit on net primary productivity
      of an Australian woodland and their interactions with drought as potential causal
      agents in recent widespread forest mortality. 

PMID- 24567833
TI  - Combining genetic and demographic data for prioritizing conservation actions:
      insights from a threatened fish species.
AB  - Prioritizing and making efficient conservation plans for threatened populations
      requires information at both evolutionary and ecological timescales.
      Nevertheless, few studies integrate multidisciplinary approaches, mainly because
      of the difficulty for conservationists to assess simultaneously the evolutionary
      and ecological status of populations. Here, we sought to demonstrate how
      combining genetic and demographic analyses allows prioritizing and initiating
      conservation plans. To do so, we combined snapshot microsatellite data and a 30
      year-long demographic survey on a threatened freshwater fish species
      (Parachondrostoma toxostoma) at the river basin scale. Our results revealed low
      levels of genetic diversity and weak effective population sizes (<63 individuals)
      in all populations. We further detected severe bottlenecks dating back to the
      last centuries (200-800 years ago), which may explain the differentiation of
      certain populations. The demographic survey revealed a general decrease in the
      spatial distribution and abundance of P. toxostoma over the last three decades.
      We conclude that demo-genetic approaches are essential for (1) identifying
      populations for which both evolutionary and ecological extinction risks are high;
      and (2) proposing conservation plans targeted toward these at risk populations,
      and accounting for the evolutionary history of populations. We suggest that demo
      genetic approaches should be the norm in conservation practices. We combined
      genetic and demographic data from a threatened freshwater fish species
      (Parachondrostoma toxostoma) at the river basin scale for conservation purposes.
      Genetic diversity and effective population sizes are very low, probably due to
      the strong genetic bottlenecks detected in this study. The species spatial
      distribution and abundance also decreased during the last decades. 

PMID- 24567835
TI  - Opposing effects on glutathione and reactive oxygen metabolites of sex, habitat,
      and spring date, but no effect of increased breeding density in great tits (Parus
      major).
AB  - Oxidative stress (i.e., more oxidants than antioxidants) has been proposed as a
      proximate currency in life-history trade-offs, which if studied in an ecological
      setting allow a more realistic perspective on the origin and evolution of trade
      offs. Therefore, the aim here was to investigate the impact of ecological and
      individual factors for variation in markers of oxidative stress using both
      experimental and correlational data. Total glutathione (tGSH), oxidized
      glutathione (GSSG), plasma antioxidant capacity (OXY), and plasma-reactive oxygen
      metabolites (ROM) were measured in more than 700 breeding great tits (Parus
      major). The main results revealed a pronounced sex difference, with females
      having lower ROM and OXY, but higher tGSH compared with males. In addition, birds
      breeding in the evergreen areas had higher tGSH compared with those in the
      deciduous habitat, but the experimentally manipulated breeding density had no
      significant effect on any of the redox markers. Independent of the sex
      differences, the larger the reproductive investment the lower the ROM of both
      males and females. Taken together, the extracellular markers - ROM and OXY -
      revealed similar results and were highly correlated. Interestingly, the direction
      of their effects was in the opposite direction to the endogenously synthesized
      tGSH and GSSG. This highlights the need to combine extracellular markers with
      endogenously synthesized antioxidants to understand its implications for the
      origin and evolution of trade-offs in an ecological setting. Oxidative stress has
      been proposed as a proximate currency in life-history trade-offs, which if
      studied in an ecological setting allow a more realistic perspective on the origin
      and evolution of trade-offs. Here multiple markers of oxidative stress were
      analysed in wild great tits. The results reveal that the endogenously synthesized
      antioxidant glutathione and markers of plasma oxidative stress are affected in
      opposing directions with regard to sex, habitat type, and spring date. Clutch
      size was negatively associated with oxidative damage, which suggests that those
      with high reproductive investment can combat physiological costs linked to
      oxidative stress. The experimentally manipulated breeding density did not
      influence oxidative stress physiology. The study highlights the need to measure
      multiple markers to understand the role of oxidative stress in limiting the
      expression of life-history traits and trajectories in different ecological
      contexts. 

PMID- 24567836
TI  - The use of statistical tools in field testing of putative effects of genetically
      modified plants on nontarget organisms.
AB  - To fulfill existing guidelines, applicants that aim to place their genetically
      modified (GM) insect-resistant crop plants on the market are required to provide
      data from field experiments that address the potential impacts of the GM plants
      on nontarget organisms (NTO's). Such data may be based on varied experimental
      designs. The recent EFSA guidance document for environmental risk assessment
      (2010) does not provide clear and structured suggestions that address the
      statistics of field trials on effects on NTO's. This review examines existing
      practices in GM plant field testing such as the way of randomization,
      replication, and pseudoreplication. Emphasis is placed on the importance of
      design features used for the field trials in which effects on NTO's are assessed.
      The importance of statistical power and the positive and negative aspects of
      various statistical models are discussed. Equivalence and difference testing are
      compared, and the importance of checking the distribution of experimental data is
      stressed to decide on the selection of the proper statistical model. While for
      continuous data (e.g., pH and temperature) classical statistical approaches - for
      example, analysis of variance (ANOVA) - are appropriate, for discontinuous data
      (counts) only generalized linear models (GLM) are shown to be efficient. There is
      no golden rule as to which statistical test is the most appropriate for any
      experimental situation. In particular, in experiments in which block designs are
      used and covariates play a role GLMs should be used. Generic advice is offered
      that will help in both the setting up of field testing and the interpretation and
      data analysis of the data obtained in this testing. The combination of decision
      trees and a checklist for field trials, which are provided, will help in the
      interpretation of the statistical analyses of field trials and to assess whether
      such analyses were correctly applied. We offer generic advice to risk assessors
      and applicants that will help in both the setting up of field testing and the
      interpretation and data analysis of the data obtained in field testing. 

PMID- 24567839
TI  - Obesity prevention in defined (high school) populations.
AB  - BACKGROUND: A challenge for the widespread dissemination of Internet-based
      programs designed to produce weight maintenance/loss in defined (high school)
      populations is to adapt them to local needs and interests, whereas demonstrating
      effectiveness and salience for both universal and targeted populations.
      OBJECTIVE: The objective of this study is to examine the feasibility of providing
      an inexpensive, Internet-based universal (healthy weight regulation) and targeted
      (weight maintenance/loss) health program to all ninth-grade students in a high
      school serving a lower socioecnomic status, diverse population. DESIGN: A total
      of 118 normal-weight and 64 overweight/obese students in the same ninth-grade
      class completed a baseline screen and were allocated to a healthy weight
      regulation program or a weight-loss maintenance program. Both groups
      simultaneously received a 10-week Internet-based intervention. Program
      implementation required minimal teacher time. Measurement included self-reported
      fruit, vegetable and high-fat/-calorie food consumption, self-reported change in
      body mass index (BMI), weight and shape concerns, as well as program engagement.
      RESULTS: The program was successfully implemented in nine classes, with minimal
      help from the investigators. There was a significant increase in self-reported
      consumption of fruits and vegetables (P=0.001). There was a significant reduction
      in self-reported BMI in the overweight/obese group (P=0.001). Students found the
      program helpful and engaging. There was a significant reduction in weight and
      shape concerns in the high-risk female students, consistent with a reduced risk
      for the development of an eating disorder. Providing a universal and targeted
      online healthy weight regulation program to ninth-grade students is feasible and
      inexpensive. The results suggest the program can serve as 'core' for future
      studies using adaptive, continuous quality-improvement designs.

PMID- 24567837
TI  - Evolutionary ecology of intraspecific brain size variation: a review.
AB  - The brain is a trait of central importance for organismal performance and
      fitness. To date, evolutionary studies of brain size variation have mainly
      utilized comparative methods applied at the level of species or higher taxa.
      However, these studies suffer from the difficulty of separating causality from
      correlation. In the other extreme, studies of brain plasticity have focused
      mainly on within-population patterns. Between these extremes lie
      interpopulational studies, focusing on brain size variation among populations of
      the same species that occupy different habitats or selective regimes. These
      studies form a rapidly growing field of investigations which can help us to
      understand brain evolution by providing a test bed for ideas born out of
      interspecific studies, as well as aid in uncovering the relative importance of
      genetic and environmental factors shaping variation in brain size and
      architecture. Aside from providing the first in depth review of published
      intraspecific studies of brain size variation, we discuss the prospects embedded
      with interpopulational studies of brain size variation. In particular, the
      following topics are identified as deserving further attention: (i) studies
      focusing on disentangling the contributions of genes, environment, and their
      interactions on brain variation within and among populations, (ii) studies
      applying quantitative genetic tools to evaluate the relative importance of
      genetic and environmental factors on brain features at different ontogenetic
      stages, (iii) apart from utilizing simple gross estimates of brain size, future
      studies could benefit from use of neuroanatomical, neurohistological, and/or
      molecular methods in characterizing variation in brain size and architecture.
      Evolution of brain size and architecture is a widely studied topic. However, the
      majority of studies are interspecific and comparative. Here we summarize the
      recently growing body of intraspecific studies based on population comparisons
      and outline the future potential in this approach. 

PMID- 24567838
TI  - High evolutionary potential of marine zooplankton.
AB  - Open ocean zooplankton often have been viewed as slowly evolving species that
      have limited capacity to respond adaptively to changing ocean conditions. Hence,
      attention has focused on the ecological responses of zooplankton to current
      global change, including range shifts and changing phenology. Here, we argue that
      zooplankton also are well poised for evolutionary responses to global change. We
      present theoretical arguments that suggest plankton species may respond rapidly
      to selection on mildly beneficial mutations due to exceptionally large population
      size, and consider the circumstantial evidence that supports our inference that
      selection may be particularly important for these species. We also review all
      primary population genetic studies of open ocean zooplankton and show that
      genetic isolation can be achieved at the scale of gyre systems in open ocean
      habitats (100s to 1000s of km). Furthermore, population genetic structure often
      varies across planktonic taxa, and appears to be linked to the particular
      ecological requirements of the organism. In combination, these characteristics
      should facilitate adaptive evolution to distinct oceanographic habitats in the
      plankton. We conclude that marine zooplankton may be capable of rapid
      evolutionary as well as ecological responses to changing ocean conditions, and
      discuss the implications of this view. We further suggest two priority areas for
      future research to test our hypothesis of high evolutionary potential in open
      ocean zooplankton, which will require (1) assessing how pervasive selection is in
      driving population divergence and (2) rigorously quantifying the spatial and
      temporal scales of population differentiation in the open ocean. Recent attention
      has focused on the ecological responses of open ocean zooplankton to current
      global change, including range shifts and changing phenology. Here, we argue that
      marine zooplankton also are well poised for evolutionary responses to global
      change. 

PMID- 24567840
TI  - Automated Screening of Hospitalized Children for Influenza Vaccination.
AB  - BACKGROUND: This study was designed to determine whether an automated hospital
      based influenza vaccination screening program leveraging the electronic medical
      record (EMR) increases vaccination rates. METHODS: We performed a retrospective
      cohort study of all children >=6 months old admitted to medical, surgical,
      rehabilitation, or psychiatry services during influenza seasons between 2003 and
      2012 at a tertiary care pediatric hospital. We compared influenza vaccination
      rates before (preintervention phase) and after (intervention phase) the
      introduction of an automated EMR intervention that utilized a nursing-based
      electronic screening tool to determine eligibility for influenza vaccine and
      facilitated vaccine ordering without requiring involvement of a physician or
      other provider. RESULTS: Overall, 42 716 (72.8%) of the 58,648 subjects admitted
      during the study period met inclusion criteria. The intervention phase included
      20,651 admissions, of which 11 194 (54.2%) were screened. Screening increased
      significantly over time in the intervention phase (19.8%-77.1%; P < .001). In
      hospital influenza vaccination rates increased from a mean of 2.1% (n = 472) of
      all subjects preintervention phase to 8.0% (n = 1645) in the intervention phase
      (odds ratio = 6.8; 95% confidence interval, 6.14-7.47). Of the 11 194 screened
      subjects, 5505 (49.2%) were found to have already been vaccinated at the time of
      screening. The screening process identified 478 (4.3%) subjects who were unable
      to receive vaccine for medical reasons, and an additional 2865 (25.6%) whose
      caregiver refused the vaccine. CONCLUSIONS: An automated, hospital-based
      influenza vaccination program integrated into the EMR can increase vaccinations
      of hospitalized patients and provide insight into the vaccination history and
      declination reasons for children not receiving the vaccine.

PMID- 24567841
TI  - Few Patient, Treatment, and Diagnostic or Microbiological Factors, Except
      Complications and Intermittent Negative Cerebrospinal Fluid (CSF) Cultures During
      First CSF Shunt Infection, Are Associated With Reinfection.
AB  - BACKGROUND: The relationship between first and subsequent cerebrospinal fluid
      (CSF) shunt infections is poorly understood. By understanding the factors
      associated with increased risk of reinfection, researchers may provide optimal
      treatment strategies at the time of first infection. The objective of this study
      was to describe and compare children with and without CSF shunt reinfection.
      METHODS: A retrospective cohort study was performed among 118 children who
      underwent initial CSF shunt placement and developed first CSF shunt infection.
      The primary outcome variable was CSF shunt reinfection. Patient risk factors and
      medical and surgical management of initial CSF shunt placement and first CSF
      shunt infection were compared between children with and without reinfection.
      RESULTS: Of 118 children with first infection, 31 (26%) developed a reinfection
      during the study period (overall median follow-up, 2096 days). Factors associated
      with reinfection in this cohort included ventriculoatrial or complex shunt at
      initial CSF shunt placement, complications after first CSF shunt infection, and
      intermittent negative CSF cultures. CONCLUSIONS: Few patient or treatment factors
      were associated with reinfection. Factors associated with difficult-to-treat
      first CSF shunt infection, including complications after first CSF shunt
      infection and intermittent negative CSF cultures, were associated with
      reinfection. Clinicians who treat patients with unusual CSF shunts or more
      difficult first infections should have a high index of suspicion for reinfection
      after treatment is completed.

PMID- 24567842
TI  - Impact of 13-Valent Pneumococcal Conjugate Vaccination on Streptococcus
      pneumoniae Carriage in Young Children in Massachusetts.
AB  - BACKGROUND: In April 2010, a 13-valent pneumococcal conjugate vaccine (PCV13)
      replaced PCV7 for use in the United States. We evaluated rates of pneumococcal
      colonization, by serotype and antibiotic resistance, in Massachusetts communities
      where serial cross-sectional surveillance has been conducted for the past decade.
      METHODS: Nasopharyngeal swabs were obtained from children 0 to <7 years of age
      and seen by primary care providers for well child or acute illness visits in
      2001, 2004, 2007, 2009, and 2011. Pneumococcal isolates were serotyped by
      Quellung reaction and classified as PCV7 serotypes (4, 6B, 9V, 14, 18C, 19F,
      23F), additional PCV13 serotypes (1, 3, 5, 6A, 7F, 19A), or non-PCV13 serotypes.
      Changes in colonization and impact of PCV13 were assessed using generalized
      linear mixed models, adjusting for known risk factors and accounting for
      clustering by community. RESULTS: Introduction of PCV13 did not affect the rate
      of overall pneumococcal colonization (31% in 2011). Colonization with non-PCV13
      serotypes increased between 2001 and 2011 for all children (odds ratio [OR] per
      year, 1.12; 95% confidence interval [CI], 1.10, 1.15; P < .0001). 19A remained
      the second most common serotype in 2011, although a decline from 2009 was
      observed. Penicillin (7%), erythromycin (28%), ceftriaxone (10%), and clindamycin
      (10%) nonsusceptibility were commonly identified, concentrated among a small
      number of serotypes (including 19A, 35B, 15B/C, and 15A). Among healthy children
      6-23 months old, colonization with PCV13 serotypes was lower among recipients of
      PCV13 vaccine (adjusted OR, 0.30; 95% CI, 0.11, 0.78). This effect was not
      observed in 6- to 23-month-old children with a concomitant respiratory tract
      infection (adjusted OR 1.36; 95% CI, 0.66, 2.77) or children 2 to <7 years old
      (adjusted OR, 1.17; 95% CI, 0.58, 2.34). CONCLUSIONS: 13-Valent pneumococcal
      conjugate vaccine reduced the prevalence of colonization with PCV13 serotypes
      among children 6-23 months old, but its efficacy was not shown among older
      children.

PMID- 24567843
TI  - Comparison of the Safety and Immunogenicity of a Novel Quadrivalent Meningococcal
      ACWY-Tetanus Toxoid Conjugate Vaccine and a Marketed Quadrivalent Meningococcal
      ACWY-Diphtheria Toxoid Conjugate Vaccine in Healthy Individuals 10-25 Years of
      Age.
AB  - BACKGROUND: Universal immunization of adolescents against meningococcal disease
      with a quadrivalent meningococcal ACWY (MenACWY) conjugate vaccine is recommended
      in a number of countries. METHODS: In a randomized, controlled, observer-blinded,
      multicenter trial, 1016 participants, 10-25 years of age, were randomly allocated
      1:1:1 to receive a single dose of 1 of 2 lots of an investigational tetanus
      toxoid-conjugated MenACWY vaccine (MenACWY-TT) or a marketed diphtheria toxoid
      conjugated MenACWY vaccine (MenACWY-DT). The primary outcome was the
      noninferiority of the vaccine response after MenACWY-TT (lot A) compared with
      MenACWY-DT for all 4 serogroups. Vaccine response was defined as a
      postvaccination human serum bactericidal antibody (hSBA) titer against each of
      the serogroups of at least 1:8 in persons initially seronegative (<1:4) or as a 4
      fold increase in titer pre- to postvaccination in persons initially seropositive
      (>=1:4). Adverse events (AEs) after immunization were measured 4 and 31 days
      postvaccination. RESULTS: The mean age of participants was 16.3 years; 977
      (96.6%) completed the study. The noninferiority of MenACWY-TT (lot A) to the
      control vaccine in terms of the percentage of participants with hSBA vaccine
      response was demonstrated for each serogroup. Vaccine response rates ranged from
      51.0% to 82.5% for the 4 serogroups after MenACWY-TT (both lots) compared with
      39.0%-76.3% for the 4 serogroups after MenACWY-DT. Pain was the most common
      injection-site reaction reported by 50.8%-55.4% across the 3 groups. Fatigue and
      headache were the most common systemic solicited AEs, reported by 27.3%-29.2% and
      25.5%-26.4%, respectively. CONCLUSIONS: Tetanus toxoid-conjugated MenACWY vaccine
      was well tolerated and elicited an immune response that was noninferior to that
      of a marketed MenACWY-DT (www.clinicaltrials.gov NCT01165242).

PMID- 24567844
TI  - The Safety and Immunogenicity of Rotavirus Vaccination in Infants With Intestinal
      Failure.
AB  - BACKGROUND: Young children with intestinal failure are at risk for complications
      from rotavirus gastroenteritis. To date, the safety and immunogenicity of
      rotavirus vaccines in these children are not known. We hypothesized that
      rotavirus vaccination would be safe and confer immunity to infants with
      intestinal failure and a history of abdominal surgery. METHODS: The study
      population consisted of infants with early intestinal failure who required
      abdominal surgery and parenteral nutrition for necrotizing enterocolitis,
      gastroschisis, jejunoileal atresia, or meconium peritonitis. Subjects received a
      rotavirus vaccine series at the appropriate age. Safety assessments were
      performed for the first 5 days after each vaccine dose. Viral stool shedding and
      serum rotavirus antigen were measured at multiple time points after each dose of
      the vaccine. A 3-fold increase in rotavirus immunoglobulin A titer at study
      completion defined seroconversion. RESULTS: Fifteen infants were enrolled and 14
      infants completed the study protocol. Mild diarrhea, emesis, and fever were noted
      after vaccination in 33%, 40%, and 7% of subjects, respectively. No subject
      experienced postvaccine intussusception, viremia, dehydration, or required
      alterations in nutritional care. Viral stool shedding was noted in 47%, but only
      1 child shed virus beyond 2 weeks postvaccination. All subjects who were not
      considered immune at baseline developed seroconversion to rotavirus after
      vaccination. CONCLUSIONS: In infants with intestinal failure, rotavirus
      vaccination appears to be safe and immunogenic. We found no evidence for altered
      viral shedding in this population. Given the profound consequences associated
      with rotavirus infection and potential benefits of rotavirus vaccine in this
      cohort, multicenter studies focusing on vaccine efficacy are warranted.

PMID- 24567846
TI  - Microbiological and Genetic Characterization of Carbapenem-Resistant Klebsiella
      pneumoniae Isolated From Pediatric Patients.
AB  - This manuscript reports the clinical, microbiological, and genetic
      characteristics of carbapenem-resistant K. pnuemoniae isolates from pediatric
      patients at a tertiary-care children's hospital. Although there is an extensive
      body of literature describing carbapenem-resistant Klebsiella infections in
      adults, pediatric data are comparatively limited. 

PMID- 24567845
TI  - A Review of Human Herpesvirus 8, the Kaposi's Sarcoma-Associated Herpesvirus, in
      the Pediatric Population.
AB  - Human herpesvirus 8 (HHV-8), also known as Kaposi's sarcoma (KS)-associated
      herpesvirus, is the etiologic agent responsible for all types of KS. Although the
      majority of pediatric KS cases occur in sub-Saharan Africa, a rise in pediatric
      transplant KS has been reported in developed countries. In addition, HHV-8 is
      increasingly described as an infectious cause of hemophagocytic
      lymphohistiocytosis in children. Transmission of HHV-8 among children is poorly
      understood; however, the literature strongly suggests that horizontal
      transmission plays a critical role. Acute infection with HHV-8 and progression to
      KS in children may be different than in adults, and diagnosis may be overlooked.
      Currently, neither adult nor pediatric treatment guidelines exist. This review
      provides an overview of HHV-8 disease in children as it relates to epidemic KS,
      transplant KS, and other disease manifestations. The current state of the
      literature is reviewed and knowledge gaps are identified for future exploration. 

PMID- 24567848
TI  - Does ectopic cell death cause somatic mutations in the neighboring cells by
      activating transposons?
AB  - Ectopic cell death in Drosophila produces a nonautonomous inhibition of RNA
      interference (RNAi) in neighboring normal cells. The expression of transposable
      elements (TE) is increased due to this reduction in the silencing mechanism. New
      insertions of TE have been documented in mutants for RNAi functions. These
      observations raise the possibility that persistent environmental insults that
      produce cell death might increase the frequency of somatic mutations, which might
      trigger somatic genetic disease.

PMID- 24567847
TI  - Angiotensin II-Superoxide Signaling and Arterial Baroreceptor Function in Type-1
      Diabetes Mellitus.
AB  - Diabetes is a major world health problem. Growing evidence from both clinical
      trials and animal experiments has clearly confirmed that arterial baroreflex
      dysfunction is a feature of type 1 diabetes, which links to prognosis and
      mortality of the type 1 diabetic patients. The arterial baroreflex normally
      regulates the blood pressure and heart rate through sensing changes of arterial
      vascular tension by the arterial baroreceptors in the aortic arch and carotid
      sinus. The aortic baroreceptor neuron located in the nodose ganglia is a primary
      afferent component of the arterial baroreflex. The functional changes of these
      neurons are involved in the arterial baroreflex dysfunction in the type 1
      diabetes. Type 1 diabetes causes the overexpression and hyperactivation of
      hyperpolarization-activated cyclic nucleotide-gated (HCN) channels and further
      reduces cell excitability of the aortic baroreceptor neurons. The alterations of
      the HCN channels are regulated by angiotensin II-NADPH oxidase-superoxide
      signaling in the aortic baroreceptor neurons. From the present review, we can
      understand the possible mechanisms responsible for the attenuated arterial
      baroreflex in the type 1 diabetes. These findings are beneficial for improving
      quality of life and prognosis in patients with the type 1 diabetes mellitus.

PMID- 24567849
TI  - Acute effects of instrument assisted soft tissue mobilization for improving
      posterior shoulder range of motion in collegiate baseball players.
AB  - BACKGROUND: Due to the repetitive rotational and distractive forces exerted onto
      the posterior shoulder during the deceleration phase of the overhead throwing
      motion, limited glenohumeral (GH) range of motion (ROM) is a common trait found
      among baseball players, making them prone to a wide variety of shoulder injuries.
      Although utilization of instrument-assisted soft tissue mobilization (IASTM),
      such as the Graston(r) Technique, has proven effective for various injuries and
      disorders, there is currently no empirical data regarding the effectiveness of
      this treatment on posterior shoulder tightness. PURPOSE: To determine the
      effectiveness of IASTM in improving acute passive GH horizontal adduction and
      internal rotation ROM in collegiate baseball players. METHODS: Thirty-five
      asymptomatic collegiate baseball players were randomly assigned to one of two
      groups. Seventeen participants received one application of IASTM to the posterior
      shoulder in between pretest and posttest measurements of passive GH horizontal
      adduction and internal rotation ROM. The remaining 18 participants did not
      receive a treatment intervention between tests, serving as the controls. Data
      were analyzed using separate 2* 2 mixed-model analysis of variance, with
      treatment group as the between-subjects variable and time as the within-subjects
      variable. RESULTS: A significant group-by-time interaction was present for GH
      horizontal adduction ROM with the IASTM group showing greater improvements in ROM
      (11.1 degrees ) compared to the control group (-0.12 degrees ) (p <0.001). A
      significant group-by-time interaction was also present for GH internal rotation
      ROM with the IASTM group having greater improvements (4.8 degrees ) compared to
      the control group (-0.14 degrees ) (p < 0.001). CONCLUSIONS: The results of this
      study indicate that an application of IASTM to the posterior shoulder provides
      acute improvements in both GH horizontal adduction ROM and internal rotation ROM
      among baseball players. LEVEL OF EVIDENCE: 2b.

PMID- 24567850
TI  - Is there a relation between shoulder dysfunction and core instability?
AB  - BACKGROUND: Overhead athletes often suffer injury to the glenohumeral joint
      secondary to inherent instability. However, little is known about the
      relationship between core stability and shoulder dysfunction among athletes.
      PURPOSE: The purpose of this study was to analyze the difference between healthy
      athletes and those with shoulder dysfunction in regard to core stability
      measures. Secondary purpose was to explore the relationship between measures of
      core stability and measures of shoulder dysfunction. METHODS: Participants
      consisted of NCAA Division III overhead athletes (28 males, 33 females) with a
      mean age of 19.3 +/- (1.1) years, mean weight of 173.6 +/- (36.9) pounds, mean
      height of 67.8 +/- (3.5) inches. Functional questionnaires (the Kerlan-Jobe
      Orthopaedic Clinical Scale [KJOC] and the QuickDASH sports module) as well as
      Single-Leg Stance Balance Test (SLBT), Double Straight Leg Lowering Test (DLL),
      Sorensen Test, and Modified Side Plank Test were completed in a randomized order
      with consistent raters. RESULTS: MANOVA was significant at (p = .038) for the
      comparison between the experimental group and the control group for the values of
      Right SLBT. The experimental group had significantly less balance than the
      control group with means of 10.14 +/- (5.76) seconds and 18.98 +/- (15.22)
      seconds respectively. Additionally, a positive correlation was found between the
      DLL and the KJOC at (r = .394, p > .05) and a negative correlation was found
      between the Right SLBT and the Quick DASH sports module (QD) at (r = -.271, p >
      .05). DISCUSSION AND CONCLUSION: Balance deficiency was found in athletes with
      shoulder dysfunction. According to this study, greater shoulder dysfunction is
      correlated with greater balance and stability deficiency. Therapists and trainers
      should consider incorporating balance training as an integral component of core
      stability into rehabilitation of athletes with shoulder dysfunction. LEVEL OF
      EVIDENCE: 3b.

PMID- 24567851
TI  - The functional movement screening (fms)TM: an inter-rater reliability study
      between raters of varied experience.
AB  - BACKGROUND: Previous researchers have reported on the reliability of the scoring
      of the FMSTM movement screens. Those authors have reported good to excellent
      inter-rater reliability between paired raters of similar experience level (either
      novice or expert), but no comparisons of inter-rater reliability exist between a
      novice and an expert. PURPOSE: The purpose of this investigation was to examine
      the inter-rater reliability of the scoring of the FMSTM between trained novices
      and an expert rater using video records. METHODS: Twenty healthy college students
      participated. Each participant performed the series of seven functional movement
      screens. Four raters (three novices and one expert) independently scored the
      seven FMSTM tests by watching video recordings of the movements.. RESULTS: The
      mean total FMSTM score for all subjects was 14.6 +/- 1.9, and was not
      significantly different between raters (p = 0.136). For the individual tests,
      half of them had perfect agreement, while the other half ranged from slight to
      moderate agreement (33-66%). CONCLUSION:  CONCLUSION: Total FMSTM scores were
      similar among the raters, and the inter-rater reliability for a majority of the
      individual tests had as strong agreement despite the various level of experience
      of the raters scoring the FMSTM tests. CLINICAL RELEVANCE: Although there was
      mostly moderate to perfect agreement among raters, the level of experience of the
      rater scoring the FMSTM should be considered, as it appears that the expert rater
      was more critical than novice raters in the interpretation of the scoring
      criteria. LEVEL OF EVIDENCE: Level 3.

PMID- 24567852
TI  - Relationship between functional movement screening score and history of injury.
AB  - BACKGROUND AND AIM: The Functional Movement Screen (FMSTM) is a screening
      instrument that evaluates selective fundamental movement patterns. The main aim
      of this study was to investigate the relationship between the FMSTM score and
      history of injury, and attempt to determine which active students are prone to
      injury. METHODS: One hundred physically active (50 females and 50 males)
      students, between 18 and 25 years of age, with no recent (<6 weeks) history of
      musculoskeletal injury were recruited. All participants performed the FMSTM and
      were scored using the previously established standardized FMSTM criteria. The chi
      square, independent t-test, one-way analysis of variance, and POSTHOC Bonferroni
      tests were used for data analysis with a preset alpha value of p < 0.05. RESULTS:
      Of the 100 subjects, 35 suffered an acute lower extremity (ankle = 20, knee = 15)
      injury in practice or competition. An odds ratio was calculated at 4.70, meaning
      that an athlete had an approximately 4.7 times greater chance of suffering a
      lower extremity injury during a regular competitive season if they scored less
      than 17 on the FMSTM. There were statistical differences between the pre-season
      FMSTM scores of the injured and non-injured groups, the ankle injury, knee
      injury, and non-injured groups, and also between contact injury, non-contact
      injury, and non-injured groups. DISCUSSION AND CONCLUSION: This cross-sectional
      study provides FMSTM reference values for physically active students, which will
      assist in the interpretation of individual scores when screening athletes for
      musculoskeletal injury and performance factors. More research is still necessary
      before implementing the FMSTM into a pre-participation physical examination (PPE)
      for athletics, but due to the low cost and its simplicity to implement, it should
      be considered by clinicians and researchers in the future. LEVEL OF EVIDENCE: 2B.

PMID- 24567853
TI  - Breathing pattern disorders and functional movement.
AB  - STUDY DESIGN: Experimental design. BACKGROUND: Normal breathing mechanics play a
      key role in posture and spinal stabilization. Breathing Pattern Disorders (BPD)
      have been shown to contribute to pain and motor control deficits, which can
      result in dysfunctional movement patterns. The Functional Movement ScreenTM
      (FMSTM) has been shown to accurately predict injury in individuals who
      demonstrate poor movement patterns. The role BPD play on functional movement is
      not well established. Furthermore, there is currently no single test to
      clinically diagnose BPD. A variety of methods are used, but correlations between
      them are poor. PURPOSE: To examine the relationship between BPD and functional
      movement and identify correlations between different measures of BPD. METHODS:
      Breathing was assessed in 34 healthy individuals using a multi-dimensional
      approach that included biomechanical, biochemical, breathing related symptoms,
      and breathing functionality measures. Movement was assessed using the FMSTM.
      Analysis, involving independent t-tests and Pearson correlation were performed to
      identify associations between measures. RESULTS: Individuals who exhibited
      biochemical and biomechanical signs of BPD were significantly more likely to
      score poorly on the FMSTM. These studied measures of BPD correlated highly with
      each other. CONCLUSION: These results demonstrate the importance of diaphragmatic
      breathing on functional movement. Inefficient breathing could result in muscular
      imbalance, motor control alterations, and physiological adaptations that are
      capable of modifying movement. These findings provide evidence for improved
      breathing evaluations by clinicians. LEVEL OF EVIDENCE: 2B.

PMID- 24567855
TI  - Effects of two types of trunk exercises on balance and athletic performance in
      youth soccer players.
AB  - PURPOSE/BACKGROUND: Many athletes perform trunk stabilization exercises (SE) and
      conventional trunk exercises (CE) to enhance trunk stability and strength.
      However, evidence regarding the specific training effects of SE and CE is lacking
      and there have been no studies for youth athletes. Therefore, the purpose of this
      study was to investigate the training effects of SE and CE on balance and
      athletic performance in youth soccer players. METHODS: Twenty-seven male youth
      soccer players were assigned randomly to either an SE group (n = 13) or CE group
      (n = 14). Data from nineteen players who completed all training sessions were
      used for statistical analyses (SE, n = 10; CE, n = 9). Before and after the 12
      week intervention program, pre- and post-testing comprised of a static balance
      test, Star Excursion Balance Test (SEBT), Cooper's test, sprint, the Step 50,
      vertical jump, and rebound jump were performed. After pre-testing, players
      performed the SE or CE program three times per week for 12 weeks. A two-way
      repeated-measures ANOVA was used to assess the changes over time, and differences
      between the groups. Within-group changes from pre-testing to post-testing were
      determined using paired t-tests. Statistical significance was inferred from p <
      0.05. RESULTS: There were significant group-by-time interactions for
      posterolateral (p = 0.022) and posteromedial (p < 0.001) directions of the SEBT.
      Paired t-tests revealed significant improvements of the posterolateral and
      posteromedial directions in the SE group. Although other measurements did not
      find group-by-time interactions, within-group changes were detected indicating
      significant improvements in the static balance test, Cooper's test, and rebound
      jump in the only SE group (p < 0.05). Vertical jump and sprint were improved
      significantly in both groups (p < 0.05), but the Step 50 was not improved in
      either group (p > 0.05). CONCLUSIONS: Results suggested that the SE has specific
      training effects that enhance static and dynamic balance, Cooper's test, and
      rebound jump. LEVEL OF EVIDENCE: 3b.

PMID- 24567854
TI  - The influence of upper body fatigue on dynamic standing balance.
AB  - PURPOSE/BACKGROUND: Muscle fatigue is related to a decline in force output and
      proprioception. These can ultimately have an adverse effect on neuromuscular
      control and functional performance. Local muscle fatigue has been shown to have
      adverse consequences on dynamic standing balance; however, much less is known
      regarding the relationship between distant fatigue and dynamic standing. The
      purpose of this study was to investigate the effects of upper body fatigue on
      dynamic standing balance. It was hypothesized that distant fatigue in upper body
      musculature would show a significant decrease in dynamic standing balance as
      assessed by the Lower Quarter Y-Balance Test (YBT-LQ). METHODS: TWENTY HEALTHY
      INDIVIDUALS (AGE: 25.0 +/- 3.42 years, height: 172.72 +/- 13.11 cm, mass: 71.36
      +/- 13.50 kg) participated in this study. A kayak ergometer was used to implement
      a fatigue protocol for the upper body. The protocol consisted of a graded
      intensity session ranging from 50% to 90% of maximum effort lasting ten minutes
      in duration (2 minutes each at 50% 60%, 70%, 80%, and 90%). The anterior (ANT),
      posteromedial (PM), and posterolateral (PL) reach directions were normalized to
      leg length and measured on the YBT-LQ before and after the fatigue protocol for
      each participant. A fourth value termed overall balance was calculated as the sum
      of the furthest reach distance of the three directions. Blood lactate analysis
      taken before and immediately after the fatigue protocol was used to quantify
      fatigue. Multiple paired t-tests were performed for pre-fatigue and post-fatigue
      balance assessment. A Bonferroni correction was applied to set the significance
      value <=0.0125 a priori. Effect size was calculated using the effect size index.
      RESULTS: Blood lactate values immediately following the fatigue protocol had an
      average concentration of 6.15 millimoles (pre: 2.3, post: 8.4). The ANT reach
      direction (rho = 0.004) and the calculated overall balance (rho = 0.011)
      significantly decreased post-fatigue in the dominant lower extremity. No
      significant differences were found for the PM (rho = 0.017) or PL (rho = 0.021)
      directions. The ANT reach direction (0.64) and overall balance (0.44) also showed
      a moderate effect size based on the effect size index. CONCLUSIONS: ANT and
      overall dynamic standing balance were negatively affected after completing the
      upper body fatigue protocol. The findings of this research demonstrate that upper
      body fatigue has adverse effects on dynamic standing balance, as measured by
      performance on the YBT-LQ. Significant and clinically relevant differences were
      noted in ANT and overall dynamic standing balance. CLINICAL RELEVANCE: Physical
      therapists should be aware of the adverse influence distant fatigue may exhibit
      on neuromuscular control in muscles not actively involved in the fatiguing
      exercise. The balance deficits noted may indicate an increased risk of injury
      with muscle fatigue in muscles not directly contributing to standing balance.
      LEVEL OF EVIDENCE: 3b, Case-control study.

PMID- 24567856
TI  - The impact of sagittal plane hip position on isometric force of hip external
      rotator and internal rotator muscles in healthy young adults.
AB  - PURPOSE/BACKGROUND: Hip external rotator (ER) and internal rotator (IR) muscle
      weakness is theorized to be associated with lower extremity injury in athletes
      including knee ligament tears and patellofemoral pain. Previous studies
      investigating hip musculature strength have utilized various sagittal plane hip
      positions for testing. The relationship between results at these different
      positions is unknown. METHODS: Eighty healthy, pain-free young adults
      participated in the study: 40 female, mean age 22.90 (+/- 2.32) years, and 40
      male, mean age 23.50 (+/- 2.15) years. Peak isometric torque of bilateral hip ER
      and IR were tested at 90 degrees  and 0 degrees  of hip flexion with an
      instrumented dynamometer. Peak muscle forces were calculated. Peak forces were
      normalized by body mass. Mean normalized force was calculated for dominant and
      non-dominant limbs for ER and IR in both positions. Male and female data were
      analyzed separately with paired t-tests (2-tailed). Reference values for average
      muscle force and torque were calculated for dominant and non-dominant limbs for
      both hip positions. RESULTS: Hip IR normalized peak force was greater at 90
      degrees  compared to 0 degrees  flexion position bilaterally in both genders (p <
      .01). Hip ER normalized peak force was greater at 90 degrees  compared to 0
      degrees  flexion in dominant limbs of both genders and in non-dominant limbs of
      males (p < .01). Non-dominant hip ER normalized force in females was greater at
      90 degrees  versus 0 degrees  flexion; however, it was not significant (p =
      .092). Post hoc analysis of normalized average force (average over 5-second
      contraction) yielded similar results. CONCLUSION: Clinicians and researchers
      should use consistent positioning for testing of hip ER and IR strength. This
      will improve certainty of determining if a patient's strength has changed or if
      differences between groups are present. Reference values reported will be useful
      in order to determine if weakness is present and to set goals, particularly in
      cases of bilateral involvement. LEVEL OF EVIDENCE: 2b.

PMID- 24567857
TI  - Normative values of eccentric hip abduction strength in novice runners: an
      equation adjusting for age and gender.
AB  - PURPOSE: Low eccentric strength of the hip abductors, might increase the risk of
      patellofemoral pain syndrome and iliotibial band syndrome in runners. No
      normative values for maximal eccentric hip abduction strength have been
      established. Therefore the purpose of this study was to establish normative
      values of maximal eccentric hip abduction strength in novice runners. METHODS:
      Novice healthy runners (n = 831) were recruited through advertisements at a
      hospital and a university. Maximal eccentric hip abduction strength was measured
      with a hand-held dynamometer. The demographic variables associated with maximal
      eccentric hip abduction strength from a univariate analysis were included in a
      multivariate linear regression model. Based on the results from the regression
      model, a regression equation for normative hip abduction strength is presented.
      RESULTS: A SIGNIFICANT DIFFERENCE IN MAXIMAL ECCENTRIC HIP ABDUCTION STRENGTH WAS
      FOUND BETWEEN MALES AND FEMALES: 1.62 +/- 0.38 Nm/kg (SD) for males versus 1.41
      +/- 0.33 Nm/kg (SD) for females (p < 0.001). Age was associated with maximal
      eccentric hip abduction strength: per one year increase in age a -0.0045 +/-
      0.0013 Nm/kg (SD) decrease in strength was found, p < 0.001. Normative values
      were identified using a regression equation adjusting for age and gender. Based
      on this, the equation to calculate normative values for relative eccentric hip
      abduction strength became: (1.600 + (age * -0.005) + (gender (1 = male / 0 =
      female) * 0.215) +/- 1 or 2 * 0.354) Nm/kg. CONCLUSION: Normative values for
      maximal eccentric hip abduction strength in novice runners can be calculated by
      taking into account the differences in strength across genders and the decline in
      strength that occurs with increasing age. Age and gender were associated with
      maximal eccentric hip abduction strength in novice runners, and these variables
      should be taken into account when evaluating eccentric hip abduction strength in
      this group of athletes. LEVEL OF EVIDENCE: 2A.

PMID- 24567858
TI  - Electromyography during pedaling on upright and recumbent ergometer.
AB  - BACKGROUND: Ergometers are used during rehabilitation and fitness to restore
      range of motion, muscular strength, and cardiovascular fitness. The primary
      difference between upright and recumbent ergometers is that the seat and crank
      spindle are aligned nearly vertically on upright bicycles and nearly horizontally
      on recumbent ergometers. In addition, recumbent ergometers are characterized by
      large seats with backrests to provide support for the upper body and are low to
      the ground, permitting easier access for wheelchair users and individuals with
      mobility impairments. Despite the great utility of the recumbent bike, it has not
      been studied with regard to energy costs or muscular output. This is the first
      study to investigate the differences between two commercial ergometers by
      analyzing of lower limb EMG in participants who are not habitual cyclers.
      METHODS: Ten non-cyclist males with no history of musculoskeletal lower limb
      injury pedaled on standard recumbent and upright ergometers. EMG data were
      recorded from the volunteers' lower limb muscles (rectus femoris, semitendinosus,
      tibialis anterior, and medial gastrocnemius muscles). EMG signals were normalized
      to the highest EMG signals recorded for the maximum voluntary isometric
      contractions (MVIC). The peak normalized EMG value of the studied muscles over
      the average of the 10 pedal cycles was analyzed. RESULTS: The differences in
      average peak muscle activity were not statistically significant for any of the
      four muscles tested. Pedaling a recumbent ergometer resulted in greater activity
      in two (semitendinosus and tibialis anterior) of the four muscles studied. Only
      the rectus femoris muscle demonstrated greater activity during upright pedaling.
      CONCLUSION: There were no differences in the EMG activity of the muscles studied
      during pedaling on a standard recumbent and an upright stationary exercise
      ergometer at moderate workload. This increased understanding of muscle activity
      during pedaling may be useful in the development of new exercise protocols and
      therapeutic approaches. LEVEL OF EVIDENCE: 2c.

PMID- 24567859
TI  - Specific and cross over effects of massage for muscle soreness: randomized
      controlled trial.
AB  - PURPOSE/BACKGROUND: Muscle soreness can negatively interfere with the activities
      of daily living as well as sports performance. In the working environment, a
      common problem is muscle tenderness, soreness and pain, especially for workers
      frequently exposed to unilateral high repetitive movements tasks. The aim of the
      study is therefore to investigate the acute effect of massage applied using a
      simple device Thera-band roller Massager on laboratory induced hamstring muscle
      soreness, and the potential cross over effect to the non-massaged limb. METHODS:
      22 healthy untrained men (Mean age 34 +/- 7 years; mean height 181.7 +/- 6.9 cm;
      mean weight 80.6 +/- 6.4 kg; BMI: 24.5 +/- 1.3) with no prior history of knee,
      low back or neck injury or other adverse health issues were recruited.
      Participants visited the researchers on two separate occasions, separated by 48
      hours, each time providing a soreness rating (modified visual analog scale 0-10),
      and being tested for pressure pain threshold (PPT) and active range of motion
      (ROM) of the hamstring muscles. During the first visit, delayed onset muscular
      soreness of the hamstring muscles was induced by 10 x 10 repetitions of the stiff
      legged dead-lift. On the second visit participants received either 1) 10 minutes
      of roller massage on one leg, while the contralateral leg served as a cross over
      control, or 2) Resting for 10 minutes with no massage at all. Measurement of
      soreness, PPT and ROM were taken immediately before and at 0, 10, 30 and 60 min.
      after treatment. RESULTS: There was a significant group by time interaction for
      soreness (p < 0.0001) and PPT (p = 0.0007), with the massage group experiencing
      reduced soreness and increasing PPT compared with the control group. There was no
      group by time interaction for ROM (p = 0.18). At 10 min. post massage there was a
      significant reduction in soreness of the non-massaged limb in the cross over
      control group compared to controls but this effect was lost 30 minutes post
      massage. CONCLUSION: Massage with a roller device reduces muscle soreness and is
      accompanied by a higher PPT of the affected muscle. LEVEL OF EVIDENCE: 2c;
      outcomes research.

PMID- 24567861
TI  - The preparticipation evaluation for athletes with disability.
AB  - BACKGROUND: Athletes are routinely assessed medically prior to competition.
      Although standardized preparticipation examinations (PPEs) are available for able
      bodied athletes, the literature lacks any validated equivalent for the athlete
      with disability (AWD). Since participation and level of competition is increasing
      in this population, evidence-based tools such as a standardized PPE form should
      be available for health professionals to assess AWD health and safety. AIM OF THE
      STUDY: To develop an AWD-targeted standardized preparticipation history
      evaluation (PPE history) using consensus-based expert recommendations. METHODS:
      Researchers developed a PPE history for critical evaluation of its content
      validity. Structured Delphi method for collecting and interpreting contributions
      from an expert panel using a series of questionnaires with controlled feedback
      was performed. Opinions based on the experience of related experts -
      physiotherapists, sports medicine physicians and physiatrists - were studied
      during each of the three survey rounds. The process was terminated once adequate
      consensus relating to the proposed PPE history document was reached. RESULTS:
      Majority consensus was reached for forty-nine of fifty-four items to create a
      refined ten section AWD-specific document to supplement the current standardized
      PPE. Modifications were made by researchers to accommodate the five items that
      did not reach statistical consensus. CONCLUSION: Consensus was reached on a
      variety of AWD-specific PPE items, including the disability-related history and
      functional review. Equipment issues represent a complex area of evaluation,
      worthy of future research and discussion. The current proposed PPE history tool
      is considered comprehensive and ready for application in a clinical setting as an
      adjunct to existing PPE tools. Injury research in the AWD population will provide
      guidance for refinement and further validation of this PPE history document.
      LEVEL OF EVIDENCE: 5.

PMID- 24567860
TI  - Roller massager improves range of motion of plantar flexor muscles without
      subsequent decreases in force parameters.
AB  - BACKGROUND: Limited dorsiflexion range of motion (ROM) has been linked to lower
      limb injuries. Improving limited ankle ROM may decrease injury rates. Static
      stretching (SS) is ubiquitously used to improve ROM but can lead to decreases in
      force and power if performed prior to the activity. Thus, alternatives to improve
      ROM without performance decrements are needed. OBJECTIVES/PURPOSE: To compare the
      effects of SS and self massage (SM) with a roller massage of the calf muscles on
      ankle ROM, maximal voluntary contraction (MVC) force F100 (force produced in the
      first 100 ms of the MVC), electromyography (EMG of soleus and tibialis anterior)
      characteristics of the plantar flexors, and a single limb balance test. METHODS:
      Fourteen recreationally trained subjects were tested on two separate occasions in
      a randomized cross-over design. After a warm up, subjects were assessed for
      passive dorsiflexion ROM, MVC, and a single-limb balance test with eyes closed.
      The same three measurements were repeated after 10 minutes (min) of rest and
      prior to the interventions. Following the pre-test, participants randomly
      performed either SS or SM for 3 sets of 30 seconds (s) with 10s of rest between
      each set. At one and 10 min post-interventions the participants repeated the
      three measurements, for a third and fourth cycle of testing. RESULTS: Roller
      massage increased and SS decreased maximal force output during the post-test
      measurements, with a significant difference occurring between the two
      interventions at 10 min post-test (p < 0.05, ES = 1.23, 8.2% difference). Both
      roller massage (p < 0.05, ES = 0.26, ~4%) and SS (p < 0.05, ES = 0.27, ~5.2%)
      increased ROM immediately and 10 min after the interventions. No significant
      effects were found for balance or EMG measures. CONCLUSIONS: Both interventions
      improved ankle ROM, but only the self-massage with a roller massager led to small
      improvements in MVC force relative to SS at 10 min post-intervention. These
      results highlight the effectiveness of a roller massager relative to SS. These
      results could affect the type of warm-up prior to activities that depend on high
      force and sufficient ankle ROM. LEVEL OF EVIDENCE: 2c.

PMID- 24567862
TI  - Treatment of subacute posterior knee pain in an adolescent ballet dancer
      utilizing trigger point dry needling: a case report.
AB  - STUDY DESIGN: Case Report. BACKGROUND AND PURPOSE: Dry needling (DN) is an
      increasingly popular intervention used by clinicians as a treatment of regional
      neuromusculoskeletal pain. DN is an invasive procedure that involves insertion of
      a thin monofilament needle directly into a muscle trigger point (MTP) with the
      intent of stimulating a local twitch response. Current evidence is somewhat
      limited, but recent literature supports the use of this intervention in specific
      neuromusculoskeletal conditions. The purpose of this case report is to present
      the outcomes of DN as a primary treatment intervention in an adolescent subject
      with subacute posterior knee pain. CASE DESCRIPTION: The subject was a 16-year
      old female competitive ballet dancer referred to physical therapy with a two
      month history of right posterior knee pain. Palpation identified MTPs which
      reproduced the patient's primary symptoms. In addition to an exercise program
      promoting lower extremity flexibility and hip stability, the subject was treated
      with DN to the right gastrocnemius, soleus, and popliteus muscles. OUTCOMES: The
      subject reported being pain free on the Numerical Pain Scale and a +7 improvement
      in perceived change in recovery on the Global Rating of Change at final follow
      up. Physical examination demonstrated no observed impairments or functional
      limitations, including normal mobility, full strength, and unrestricted execution
      of dance maneuvers. DISCUSSION: The patient was able to return to high level
      dance training and competition without physical limitations and resumed pre
      injury dynamic movement activities including dancing, running, jumping, and
      pivoting without pain. DN can be an effective and efficient intervention to
      assist patients in decreasing pain and returning to high intensity physical
      activity. Additional research is needed to determine if DN is effective for other
      body regions and has long-term positive outcomes. LEVEL OF EVIDENCE: Level 4.

PMID- 24567863
TI  - Chronic leg pain in a division ii field hockey player: a case report.
AB  - Exertional compartment syndromes in athletes represent a diagnostic and
      management challenge for clinicians. The clinical presentation of exertional
      compartment syndrome is similar to other more common musculoskeletal disorders. A
      lack of special tests or unique diagnostic identifiers for use in decision making
      by out-patient clinicians complicates early recognition of this disorder and may
      delay optimal management. The purpose of this case report is to retrospectively
      explore the clinical presentation and the decision-making during the course of
      care of a field hockey athlete eventually determined to have exertional
      compartment syndrome. Suggestions to assist in recognition and guidance in
      patient management are included as well as the procedures required for
      differential diagnosis. Procedures utilized during conservative care are also
      described in detail. LEVEL OF EVIDENCE: 5 (Single Case Report).

PMID- 24567864
TI  - Generalization of Conditioned Fear and Obsessive-Compulsive Traits.
AB  - Generalization of conditioned fear refers to the transfer of the conditioned fear
      response to stimuli that resemble the original conditioned stimulus.
      Overgeneralization of conditioned fear has been associated with panic disorder
      and generalized anxiety disorder and may be relevant to obsessive-compulsive (OC)
      symptoms as well. This study represents the first attempt to determine the degree
      to which individuals with high versus low OC traits over generalize conditioned
      fear. We hypothesized that the high OC individuals, particularly those
      characterized by overestimation of threat, would show overgeneralization of
      conditioned fear compared to controls as measured by behavioral and
      psychophysiological (fear-potentiated startle) measures. The results of this
      study show an interaction between the high and low Threat Estimation groups as
      measured by the Obsessive Beliefs Questionnaire, which suggests that those who
      have a tendency to overestimate threat show overgeneralization of conditioned
      fear. This finding suggests that the relation between OC symptoms and
      overgeneralization of conditioned fear may be specific to the high threat
      estimation component of OC symptoms.

PMID- 24567865
TI  - Effects of Selective Neonatal Amygdala Damage on Concurrent Discrimination
      Learning and Reinforcer Devaluation in Monkeys.
AB  - OBJECTIVES: The amygdala is known to be a key neural structure in many
      neuropsychiatric disorders. Primarily known for its involvement in fear
      regulation, the amygdala also plays a critical role in appetitive flexible
      decision-making. Yet, its contribution to the development of flexible goal
      directed behavior has not been thoroughly examined. DESIGN: The current study
      examined flexible decision-making abilities after neonatal amygdala lesions in
      nonhuman primates using a behavioral paradigm known to measure the flexible
      monitoring of goal-directed choices in rodents, monkeys, and humans. METHOD:
      Rhesus monkeys of both sexes were divided into two groups, a sham-operated
      control group (N=4) and a group with neonatal neurotoxic amygdala lesions (N=5).
      Animals received the lesions at 1-2 weeks and were tested at both four and six
      years of age on a concurrent discrimination reinforcer devaluation task. RESULTS:
      Although neonatal amygdala damage spared learning stimulus-reward associations,
      it severely impaired the ability to flexibly shift object choices away from those
      items associated with devalued food rewards. The results were similar to those
      obtained in monkeys that had acquired the same lesions in adulthood. CONCLUSIONS:
      Thus, the amygdala is critical for appetitive decision-making, and provide
      further evidence of little functional sparing after early amygdala insult. The
      findings are discussed in relation to other behavioral measures on the same
      animals and to clinical neuropsychiatric disorders.

PMID- 24567866
TI  - beta-catenin-mediated inhibition of cross-priming: A new mechanism for tumors to
      evade immunosurveillance.
AB  - Cross-priming plays a major role in generating CD8+ T cell-dependent antitumor
      immunity through cross-presentation. However, the cross-presentation of tumor
      associated antigens by dendritic cells often promotes tolerance rather than CD8+
      T-cell immunity. We have now identified a beta-catenin-dependent pathway of cross
      priming inhibition as a novel and potentially broad mechanism whereby neoplastic
      cells promote immunosuppression.

PMID- 24567867
TI  - Examining e-Health literacy and the digital divide in an underserved population
      in Hawai'i.
AB  - Seeking health information is one of the leading uses for the Internet and World
      Wide Web (WWW). Research has found the amount one benefits from e-Health
      information (health information from electronic sources) is directly related to
      the level of e-Health literacy. e-Health literacy is defined as "the ability to
      seek, find, understand, and appraise health information from electronic sources
      and apply the knowledge gained to addressing or solving a health problem." In
      order to gain a further understanding of the effects and use of technology, the
      digital divide, and the relationship between technology utilization and health
      outcomes, focus group interviews were conducted with participants diagnosed with
      diabetes and currently residing in a Medically Underserved Area. Overall, 25
      volunteers participated in the four focus group meetings. Based on the focus
      group discussions, a general low e-Health literacy rate was identified. This was
      demonstrated by the lack of access to the Internet and the skills needed to
      retrieve health information. Of the 25 participants, 64% reported having Internet
      access at some level, but, only one reported going on the Internet every day.
      When the barriers to using the Internet were discussed, many participants
      expressed a lack of knowledge in how to retrieve information. Results of this
      study further show that having access to technology is not necessarily associated
      with usage. This dynamic is evolving into a new form of digital divide, gap in
      information retrieval and usage, versus gap in access. This is the first known
      study to examine e-Health literacy in an underserved population in Hawai'i. With
      the proliferation of information and communication technology and the
      transformation of information retrieval to be mobile and "on demand", a multi
      pronged communication and education strategy is needed to explore how technology
      can improve e-Health literacy and health outcomes among underserved populations.

PMID- 24567869
TI  - Diagnosis of intussusception using bedside ultrasound by a pediatric resident in
      the emergency department.
AB  - The use of bedside ultrasound in the emergency department has been gaining favor
      among emergency medicine physicians and can be invaluable in the prompt diagnosis
      and treatment of acutely ill patients, especially when radiology evaluation is
      unavailable or delayed. Although pediatric ultrasound examinations are taught in
      some pediatric residency programs, they are not part of the required pediatric
      residency curriculum in the United States. This is the first case report of a
      pediatric resident diagnosing intussusception by bedside ultrasound in a 4-year
      old boy under the guidance of a pediatric emergency attending with ultrasound
      training. This report illustrates the ease of using bedside ultrasound even among
      early learners and highlights its potential importance in medical education for
      fellows and residents.

PMID- 24567868
TI  - Maternal asthma, diabetes, and high blood pressure are associated with low birth
      weight and increased hospital birth and delivery charges; Hawai'i hospital
      discharge data 2003-2008.
AB  - Asthma, diabetes, and high blood pressure are common maternal conditions that can
      impact birth outcomes. Data from hospital discharges in Hawai'i were analyzed for
      107,034 singleton births from 2003-2008. Categories were determined using the
      International Statistical Classification of Diseases, ninth revision (ICD-9) from
      linked delivery records of mother and infant. Prevalence estimates of asthma (ICD
      9: 493), diabetes (ICD-9: 250,648.0, 648.8), high blood pressure (ICD-9: 401
      405,642) as coded on the delivery record, low birth weight (<2500 grams), high
      birth weight (>4500 grams), Cesarean delivery, and median hospital charges were
      calculated. Median regression analysis assessed total hospital charges adjusting
      for maternal age, maternal race, insurance, and Cesarean delivery. Maternal
      asthma was present in 4.3% (95% confidence interval=4.1-4.4%), maternal diabetes
      was present in 7.7% (95% CI=7.6-7.9%), and maternal high blood pressure was
      present in 9.2% (95% CI=9.0-9.3%) of births. In the adjusted median regression
      analysis, mothers with asthma had $999 (95% CI: $886 to $1,112) higher hospital
      charges compared to those without; mothers with diabetes had $743 (95% CI: $636
      to $850) higher charges compared to those without; and mothers with high blood
      pressure had $2,314 (95% CI: $2,194 to $2,434) higher charges compared to those
      without. Asthma, diabetes, and high blood pressure are associated with higher
      hospital delivery charges and low birth weight. Diabetes and high blood pressure
      were also associated with Cesarean delivery. An increased awareness of the impact
      of these conditions on both adverse birth outcomes and the development of chronic
      disease is needed.

PMID- 24567870
TI  - The relationship of decongestant use and risk of decompression sickness; a case
      control study of Hawaiian scuba divers.
AB  - Exposure to cold, dehydration, and aging are known to contribute to the
      development of decompression sickness (DCS) in divers. Hypertension and nicotine
      usage have also been suggested as risk factors. Vasoconstriction is an underlying
      mechanism associated with all of these risk factors. Vasoconstriction increases
      the degree of bubble formation which is believed to be the cause of DCS. Formed
      bubbles interfere with the production of nitric oxide which modulates vascular
      tone resulting in vasoconstriction. Divers commonly use sympathomimetic
      decongestants which induce vasoconstriction to prevent barotrauma of the ears and
      sinuses while diving and thus theoretically may contribute to the risk for
      developing DCS. The purpose of this case-control study was to explore the
      association between decongestant usage and development of DCS in 400 divers
      treated/evaluated at the University of Hawai'i, John A. Burns School of Medicine
      between 1983 and 2010. Bivariate and logistic regression analyses were employed
      to evaluate differences between cases and controls. In addition to the variable
      of interest, other co-variables known to have significant influence in the
      development of DCS were appropriately controlled for during the analyses. In this
      study population, dehydration (OR = 2.7; 95% CI: 1.1, 7.4), repetitive diving (OR
      = 2.8; 95% CI: 1.8, 4.4), and violation of dive profiles (OR = 4.9; 95% CI: 3.1,
      7.9) contributed independently and significantly to the development of DCS. The
      co-variables of cold, gender, obesity, and rapid ascents were not significant
      contributors to developing DCS in this study. There was a small but statistically
      insignificant risk associated with decongestant use (OR = 1.4; 95% CI: 0.8-2.6; P
      = .22). The inherent limitations associated with records-based studies may have
      underestimated this risk. It is important therefore that future research be
      undertaken to help clarify this concern.

PMID- 24567871
TI  - Medical school hotline: Celebrating 40 years of 'Imi Ho'ola.

PMID- 24567872
TI  - Insights in public health: The Hawai'i-China public health partnership.

PMID- 24567874
TI  - Effect of Millettia ferruginea (Birbra) foliage supplementation on feed intake,
      digestibility, body weight change and carcass characterstics of Washera sheep fed
      natural pasture grass hay basal diet.
AB  - Twenty-four yearling male local Washera lambs with an average initial body weight
      of 18.14 +/- 1.07 kg were used to assess the nutritional value of Millettia
      ferruginea. Experimental animals were grouped into six blocks of four animals,
      and each animal was randomly assigned to one of the four dietary treatment feeds.
      The treatments used were; Sole natural pasture grass hay (T1), and 150, 300, 450
      g DM Millettia ferruginea leaf hay with ad libitum natural pasture grass hay
      assigned for (T2), (T3) and (T4), respectively. The feeding trial was carried out
      for 80 days followed by a 10 days of digestibility trial. Carcasses of each
      experimental animal were evaluated at the end of the digestibility experiment.
      Millettia ferruginea leaf hay had 224.6, 556.6, 360.7and 127.4 g/kg crude protein
      (CP), neutral detergent fiber (NDF), acid detergent fiber (ADF) and acid
      detergent lignin (ADL), respectively. The average intakes of Millettia ferruginea
      leaf hay were 0, 133, 263 and 253 g/day for T1, T2, T3 and T4, in that order. The
      proportions of Millettia ferruginea leaf hay intake from the total dry matter
      (DM) were 0, 23.5, 44.1, and 43.3% for T1, T2, T3 and T4, respectively. The total
      DM intake was not significant but showed a trend of T1 > T3 > T4 > T2. CP intake
      was higher for T3 and T4 with the least intake for T1. Final body weight
      measurement was higher for T3 and T1 but lower and negative for T2 and T4.
      Generally, body weight measurements were not consistent in the supplemented
      groups throughout the trial period. The weight of heart, spleen, and liver were
      higher for the supplemented groups compared to the sole grass hay. From the
      results of the current study, it can be concluded that, Millettia ferruginea had
      some limiting factors, which prevented the animal from efficiently utilize it.
      Therefore, this study revealed the indispensable role of animal feeding
      experiments with target animals to examine such impacts. 

PMID- 24567875
TI  - Using satellite data to monitor land-use land-cover change in North-eastern
      Latvia.
AB  - Land-use and land-cover change (LULCC), especially those caused by human
      activities, is one of the most important components of global environmental
      change (Jessen 3(rd) edition: 1-526 2005). In this study the effects of
      geographic and demographic factors on LULCC are analyzed in northeastern Latvia
      using official estimates from census and vital statistics data, and using
      remotely sensed satellite imagery (Landsat Thematic Mapper) acquired from 1992
      and 2007. The remote sensing images, elevation data, in-situ ground truth and
      ground control data (using GPS), census and vital statistics data were processed,
      integrated, and analyzed in a geographic information system (GIS). Changes in six
      categories of land-use and land-cover (wetland, water, agriculture, forest, bare
      field and urban/suburban) were studied to determine their relationship to
      demographic and geographic factors between 1992 and 2007. Supervised
      classifications were performed on the Landsat images. Analysis of land cover
      change based on "change-to" categories between the 1992 and 2007 images revealed
      that changes to forest were the most common type of change (17.1% of pixels),
      followed by changes to agriculture (8.6%) and the fewest were changes to
      urban/suburban (0.8%). Integration of population data and land-cover change data
      revealed key findings: areas near to roads underwent more LULCC and areas far
      away from Riga underwent less LULCC. Range in elevation was positively correlated
      with all LULCC categories. Population density was found to be associated with
      most LULCC categories but the direction of effect was scale dependent. This paper
      shows how socio-demographic data can be integrated with satellite image data and
      cartographic data to analyze drivers of LULCC at multiple spatial scales. 

PMID- 24567876
TI  - Volume-rendered hemorrhage-responsible arteriogram created by 64 multidetector
      row CT during aortography: utility for catheterization in transcatheter arterial
      embolization for acute arterial bleeding.
AB  - Aortography for detecting hemorrhage is limited when determining the catheter
      treatment strategy because the artery responsible for hemorrhage commonly
      overlaps organs and non-responsible arteries. Selective catheterization of
      untargeted arteries would result in repeated arteriography, large volumes of
      contrast medium, and extended time. A volume-rendered hemorrhage-responsible
      arteriogram created with 64 multidetector-row CT (64MDCT) during aortography
      (MDCTAo) can be used both for hemorrhage mapping and catheter navigation. The
      MDCTAo depicted hemorrhage in 61 of 71 cases of suspected acute arterial bleeding
      treated at our institute in the last 3 years. Complete hemostasis by embolization
      was achieved in all cases. The hemorrhage-responsible arteriogram was used for
      navigation during catheterization, thus assisting successful embolization.
      Hemorrhage was not visualized in the remaining 10 patients, of whom 6 had a
      pseudoaneurysm in a visceral artery; 1 with urinary bladder bleeding and 1 with
      chest wall hemorrhage had gaze tamponade; and 1 with urinary bladder hemorrhage
      and 1 with uterine hemorrhage had spastic arteries. Six patients with
      pseudoaneurysm underwent preventive embolization and the other 4 patients were
      managed by watchful observation. MDCTAo has the advantage of depicting the
      arteries responsible for hemoptysis, whether from the bronchial arteries or other
      systemic arteries, in a single scan. MDCTAo is particularly useful for
      identifying the source of acute arterial bleeding in the pancreatic arcade area,
      which is supplied by both the celiac and superior mesenteric arteries. In a case
      of pelvic hemorrhage, MDCTAo identified the responsible artery from among
      numerous overlapping visceral arteries that branched from the internal iliac
      arteries. In conclusion, a hemorrhage-responsible arteriogram created by 64MDCT
      immediately before catheterization is useful for deciding the catheter treatment
      strategy for acute arterial bleeding. 

PMID- 24567877
TI  - Coupling groundwater modeling and biological indicators for identifying
      river/aquifer exchanges.
AB  - Future climate changes and the resulting modifications in anthropogenic
      activities will alter the interactions between rivers and groundwater. The
      quantification of these hydraulic interactions is absolutely necessary for
      achieving sustainable water use and requires accurate analytical methodologies.
      This report proposes an interdisciplinary approach to the quantitative and
      qualitative characterization of hydraulic interactions between rivers and shallow
      aquifers, wherein it outlines the advantages of coupling groundwater modeling
      with biological markers. As a first step, we built independent diagnostic maps of
      hydrological exchanges at the sector scale on the basis of hydrogeological
      modeling and biological indicators. In a second step, these maps were compared to
      provide a quantitative and qualitative understanding of exchanges between
      groundwater and surface water. This comparison significantly improved the
      calibration of groundwater models through a better assessment of boundary zones.
      Our approach enabled us to identify the conditions under which it could be
      possible to use biological indicators instead of a large set of piezometric
      measures. The integration of such combined tools in a future decision support
      system will assist governmental authorities in proposing appropriate long-term
      water policies for the preservation of groundwater resources, such as for
      supplying potable water and/or mitigating pollution risks. 

PMID- 24567878
TI  - Profile of international air passengers intercepted with illegal animal products
      in baggage at Guarulhos and Galeao airports in Brazil.
AB  - Protection against biological material entering a country or region through
      airports is important because, through them, infectious agents can quickly reach
      exotic destinations and be disseminated. Illegal products of animal origin may
      contain hazardous infectious agents that can compromise animal and public health.
      The aim of this study was to identify associations between possession of illegal
      animal products in baggage and demographic characteristics of the passengers, as
      well as characteristics of their travel plans in the two main Brazilian
      international airports. A total of 457 passengers were divided into two groups:
      passengers identified as carrying illegal animal products and control. Passengers
      identified as carrying illegal animal products not stated on the accompanied
      baggage declaration completed a questionnaire, to aid in profiling. Nationality,
      origin, age and residency of passengers were analyzed using chi square, logistic
      regression and odds ratios. Passengers from Eastern Europe were the most likely
      to enter with animal products as were those aged between 35 and 55 years. When
      evaluating the departure point, the highest frequency was seen in those coming
      from Portugal. Passenger group, reasons for travel, amount and type of baggage
      were available only for passengers identified as carrying illegal animal
      products, noting that they prefer traveling alone, for leisure, bringing few
      bags. Such information can contribute to the early identification of passengers
      that have illegal animal products in baggage at Brazilian airports. 

PMID- 24567879
TI  - Invasive lobular carcinoma of the breast: long-term prognostic value of Ki67 and
      histological grade, alone and in combination with estrogen receptor.
AB  - BACKGROUND: The aim of the present study was to investigate the long-term impact
      of prognostic factors in invasive lobular carcinoma (ILC) of the breast, with a
      primary focus on Ki67 and histological grade, alone and in combination with
      estrogen receptor (ER). MATERIAL AND METHODS: One hundred and ninety two well
      characterised patients with ILC were included in the study. Ki67, histological
      grade and ER were evaluated and combined into a prognostic index (KiGE). All
      grade 1 tumours and ER-positive (ER+) grade 2 tumours with Ki67 <= 30% were
      classified as low-KiGE and all the others as high-KiGE. RESULTS: Overall, 31% of
      the patients have died from breast cancer. The median follow-up of the patients
      still alive was 21 years. Age, tumour size, axillary lymph node status (nodal
      status), histological grade, Ki67 and KiGE were significant prognostic factors
      for breast cancer mortality (BCM) in univariable analysis. In a multivariable
      model, adjusted for adjuvant treatment, age and progesterone receptor (PgR), the
      strongest prognostic factors for BCM were: Nodal status (hazard ratio (HR) = 2.9,
      95% confidence interval (95% CI): 1.4-6.1), KiGE (HR = 2.0, 95% CI: 1.1-3.6), and
      tumour size (HR = 1.9, 95% CI: 0.98-3.8). By combining these three factors, 37%
      of the ILC's could be further divided into a low-risk group, consisting of node
      negative small (<= 20 mm) low-KiGE tumours, with a BCM of 5% (95% CI: 1-13%) at
      10 years and 12% (95% CI: 5-22%) at 20 years follow-up. None of these patients
      recieved chemotherapy and only 2 recieved endocrine treatment with tamoxifen.
      CONCLUSIONS: The combination of Ki67, histological grade and ER into KiGE,
      together with tumour size and nodal status make it possible to identify a large
      group of ILC patients with such a good long-term prognosis that chemotherapy can
      be safely avoided and exclusion of endocrine therapy considered.

PMID- 24567880
TI  - Treatment decisions in estrogen receptor-positive early breast cancer patients
      with intermediate oncotype DX recurrence score results.
AB  - This retrospective study evaluated the impact of intermediate Recurrence
      Score((r)) results on adjuvant treatment decisions in estrogen receptor-positive
      (ER+) early invasive breast cancer, comparing treatment recommendations pre
      testing with actual treatments received post-testing. Of the 111 patients
      included in the analysis, 78 (70.3%) had hormonal therapy (HT) and 33 (29.7%) had
      chemohormonal therapy (CHT) recommendations pre-testing. The Recurrence Score was
      significantly higher in those with a pre-testing CHT recommendation compared with
      those with a pre-testing HT recommendation (median of 24 vs. 22; P = 0.047; Mann
      Whitney-Wilcoxon [MWW] test). Post-testing, treatment of 24 patients (21.6%) was
      different from their pre-testing recommendation. The difference between CHT
      recommendation rate pre-testing and the rate of CHT received post-testing was
      nonsignificant for the entire cohort and for patients' subgroups (by age, tumor
      size, and grade) (P >0.17; McNemar's test). Following classification of the
      cohort into two Recurrence Score subcategories (low-intermediate, [18-25]; high
      intermediate, [26-30]), changes in treatment decisions (pre-testing
      recommendations vs. actual treatments received post testing) were reported for
      16.5% of low-intermediate and 34.4% of high-intermediate patients. Post-testing,
      the rate of CHT decreased (by 58%) in the low-intermediate subcategory and
      increased (by 64%) in the high-intermediate subcategory (P <0.01, both
      subcategories). In logistic regression analyses, the Recurrence Score subcategory
      was the only significant predictor of changes in treatment decisions (pre-testing
      recommendations vs. actual treatments received post testing; P <0.01). The only
      significant difference between the two subsets of patients with such a change (HT
      to CHT, 11 patients; CHT to HT, 13 patients) was the Recurrence Score (median of
      28 vs. 20, respectively; P = 0.0014; MWW test). These findings demonstrate that
      intermediate Recurrence Score results provide clinically relevant information and
      impact treatment decisions in ER + early breast cancer. 

PMID- 24567881
TI  - Effect of the loading duration on the linear viscoelastic parameters of tropical
      wood: case of Tectona grandis L.f (Teak) and Diospyros mespiliformis (Ebony) of
      Benin Republic.
AB  - Judicious and regulated use of wood as a building material is better than that of
      many other conventional materials in terms of environmental issues of this
      century. The study of the behavior of wood requires a better understanding of the
      characteristics in different possible cases of loading including loads applied
      instantly, loads applied for a short time and loads applied for a long time. The
      purpose of this study is to evaluate the influence of the loading duration on the
      linear viscoelastic parameters of tropical wood in creep test. Creep tests
      conducted on two species of tropical wood, Tectona grandis L.f and Diospyros
      mespiliformis, were carried out for a total loading duration of 15 hours by
      subjecting samples to bending test through with equal strain in all sections.
      After measuring the instantaneous deflection, the other measurements were carried
      out at regular time each 30 minutes. Each recorded deflection was converted into
      longitudinal deformation and the data were analyzed by considering fourteen
      loading durations. Using the least squares method, the dynamic modulus of
      elasticity and the modulus of dynamic viscosity were determined for each loading
      time. The results showed that the loading time has no influence on the modulus of
      dynamic viscosity. On the other hand, the dynamic modulus of elasticity decreases
      and tends towards zero. Good agreement between creep test data and dynamic
      modulus of elasticity was found using mathematical function in power. Suitably,
      the "power" function established between the elastic dynamic modulus and the
      loading duration can be used to extrapolate deformations values. 

PMID- 24567882
TI  - Comparison of three different kits for extraction of high-quality RNA from frozen
      blood.
AB  - Extraction of high-quality RNA is a crucial step in gene expression profiling. To
      achieve optimal RNA extraction from frozen blood, the performance of three RNA
      extraction kits- TRI reagent, PAXgene blood RNA system (PAXgene) and NucleoSpin
      RNA blood kit (NucleoSpin)- was evaluated. Fifteen blood specimens collected in
      tubes containing potassium ethylenediaminetetraacetic acid (EDTA) and stored at 
      80 degrees C for approximately 5 years were randomly selected. The yield and
      purity of RNA, RIN (RNA integrity number) values and cycle threshold (Ct) values
      were assessed. Mean RNA yields with TRI reagent, PAXgene and NucleoSpin were 15.6
      +/- 8.7 MUg/ml, 3.1 +/- 1.7 MUg/ml and 9.0 +/- 5.5 MUg/ml, respectively. Mean
      A260/280 ratios of RNA for the three kits were 1.7 +/- 0.1, 2.0 +/- 0.1, and 2.0
      +/- 0.0, and mean RIN values recorded as 3.2 +/- 0.8, 6.0 +/- 1.1, and 6.4 +/-
      0.9, respectively. The Ct values of housekeeping genes, 18S rRNA, beta-actin,
      RPLP0 and HPRT1, were as follows: TRI reagent (19.2 +/- 1.6, 30.6 +/- 1.8, 29.9
      +/- 1.4 and 36.3 +/- 1.3), PAXgene 16.6 +/- 1.4, 26.4 +/- 1.3, 28.2 +/- 1.8 and
      33.8 +/- 1.1), and NucleoSpin (16.3 +/- 1.5, 27.2 +/- 1.3, 27.0 +/- 1.6 and 32.9
      +/- 1.6). RNA yield using TRI reagent was 1.7 times higher than that with
      NucleoSpin and 5 times higher than that with PAXgene. However, the purity and
      integrity of TRI-extracted RNA was lower than that extracted with PAXgene and
      NucleoSpin. Moreover, the Ct values of housekeeping genes after extraction with
      TRI reagent were approximately 1.7-3.8 times higher than those obtained with
      PAXgene and NucleoSpin. The PAXgene and NucleoSpin kits produced similar results
      in terms of RNA purity and integrity and subsequent gene amplification. However,
      RNA yields from NucleoSpin were 2.9-fold higher, compared to PAXgene. Based on
      these findings, we conclude that NucleoSpin is the most effective kit for
      extraction of abundant and high-quality RNA from frozen blood. 

PMID- 24567883
TI  - Evaluation of Interactive Voice Response (IVR) and postal survey in follow-up of
      children and adolescents discharged from psychiatric outpatient treatment: a
      randomized controlled trial.
AB  - Systematic evaluation of child and adolescent psychiatric outpatient treatment is
      important but time-consuming. The aim of this paper was to study whether
      Interactive Voice Response (IVR) is a more effective method than a questionnaire
      sent by post when following up outpatient treatment in child and adolescent
      psychiatry. Eighty patients were recruited from a child and adolescent
      psychiatric outpatient unit in Sweden. One parent of each of the patients was
      randomized to complete the BCFPI follow-up form, using either IVR (n = 40) or
      postal survey (n = 40) one month after discharge. The response rate for complete
      answers was 65% in the IVR group and 38% in the postal survey group (p = 0.014).
      There was less need for reminders in the IVR group (p = 0.000). IVR is a
      promising and cost-effective method for evaluating evidence-based treatment in
      child and adolescent psychiatric care. 

PMID- 24567884
TI  - Successful neoadjuvant chemotherapy for large cell neuroendocrine carcinoma of
      the cervix: A case report.
AB  - *We present a case of cervical large cell neuroendocrine carcinoma (LCNEC) and
      neoadjuvant chemotherapy with irinotecan plus cisplatin that was extremely
      effective.*Cervical LCNEC is uncommon and highly aggressive, and optimal therapy
      has yet to be determined.*This case suggests that neoadjuvant chemotherapy
      followed by radical hysterectomy could be a useful treatment option for bulky
      cervical LCNEC. 

PMID- 24567885
TI  - Endometrial carcinoma metastatic to the clitoris: A case report.
AB  - *Skin metastasis from an endometrial carcinoma is very rare and prognosis is
      poor.*This report describes clitoral metastasis from an endometrial
      adenocarcinoma.*Clitoral and distant metastases and the primary site were
      diagnosed concomitantly. 

PMID- 24567886
TI  - Toe metastasis: A rare pattern of cervical cancer spread.
AB  - *Toe metastasis is a rare pattern of cervical cancer spread.*Enlarged
      erythematous toe is an important sign suggesting bone metastasis.*Toe metastasis
      represents a grave prognostic indicator of cervical cancer. 

PMID- 24567887
TI  - Malignant transformation of abdominal wall endometriosis with lymph node
      metastasis: Case report and review of literature.
AB  - *A simple endometriosis can result in malignancy pathology, as a neoplasia.*Wall
      abdominal tumors and soft tissue as a possible differential diagnosis of
      abdominal wall endometriosis*Preperitoneal node-metastasis as malignancy of
      endometriosis in previous cesarean scar. 

PMID- 24567888
TI  - Fertility sparing treatment of a malignant uterine perivascular epithelioid cell
      tumor: A case report.
AB  - *Perivascular epithelioid cell tumors (PEComas) are a family of rare, poorly
      defined mesenchymal tumors of uncertain malignant potential.*Treatment for
      PEComas has most commonly involved excisional biopsy or surgical resection.*The
      use of mTOR inhibitors may provide the best medical treatment as well as a
      fertility-sparing treatment option. 

PMID- 24567889
TI  - Thought suppression across time: Change in frequency and duration of thought
      recurrence.
AB  - Some studies have found that trying to suppress thoughts increases their long
      term recurrence, a phenomenon associated with psychopathology, particularly
      obsessive-compulsive disorder. However, effect sizes in thought suppression
      studies have often been small and inconsistent. The present study sought to
      improve thought suppression conceptualization and measurement by examining two
      distinct dimensions of thought recurrence - frequency and duration of a thought's
      return - and how they evolve over time. After a thought focus period, 100 adults
      were assigned to either suppress or monitor the recurrence of an unpleasant
      thought for 4 min. Then, during a second four-minute period, all participants
      were asked to monitor the thought's recurrence. Hierarchical linear modeling
      indicated that thought frequency declined across time and the rate of decline
      slowed as time went on. Initially, the extent of thought duration remained short
      and stable for those asked to suppress, and increased linearly over time for
      those asked to monitor. Later, this pattern reversed. Duration increased linearly
      for those initially asked to suppress but was short and stable for those who
      initially monitored. Accounting for change over time and means of measuring
      recurrence (frequency vs. duration) may help elucidate past mixed findings, and
      improve thought suppression research methodology.

PMID- 24567890
TI  - High weekly doses of liposomal amphotericin B as secondary prophylaxis after
      cerebral aspergillosis in a paediatric patient.
AB  - A paediatric patient treated for acute lymphoblastic leukaemia developed cerebral
      abscesses caused by Aspergillus fumigatus. After surgical draining voriconazole
      treatment was started. The patient developed a Steven-Johnson syndrome and
      treatment was switched to L-AmB. The patient developed no new fungal lesions and
      L-AmB treatment was continued until the end of the therapy. Complete remission
      was achieved without neurological consequences. High dose L-AmB represents an
      alternative for secondary prophylaxis of invasive fungal infections in patients
      intolerant to azoles. 

PMID- 24567891
TI  - Candida dubliniensis spondylodiscitis in an immunocompetent patient. Case report
      and review of the literature.
AB  - We describe what appears to be the first case of spondylodiscitis due to Candida
      dubliniensis. Our case adds to the current literature of the importance of C.
      dubliniensis as a cause of fungemia and subsequent deep seated infections. It
      highlights the importance of taking fungal as well as bacterial culture from
      biopsy specimens in patients with spondylodiscitis. We also review the literature
      covering the reported cases of Candida spondylodiscitis, which amount to about
      100 over the last 5 decades. 

PMID- 24567892
TI  - Cryptococcus albidus encephalitis in newly diagnosed HIV-patient and literature
      review.
AB  - We present the first case of encephalitis caused by Cryptococcus albidus duo to
      AIDS. In addition, we give an overview of the literature of extra-dermal
      infection cases caused by C. albidus. In the 21 cases, HIV and organ
      transplantation were important risk factors especially in recent 20 years. Fungal
      culture or India ink preparations are the best way to demonstrate C. albidus in
      both serum and CSF. 

PMID- 24567893
TI  - Case report: Enteral nutritional supplement as a likely cause of false-positive
      galactomannan testing.
AB  - The detection of galactomannan (GM) in the serum of in immunocompromised patients
      is widely used for the early diagnosis of invasive aspergillosis. We report a
      case of a false-positive GM test presumably caused by the enteral nutritional
      supplement given to a non-neutropenic patient with intestinal graft-versus-host
      disease after a hematopoietic stem cell transplant. Clinicians should be alert to
      the possibility of false-positive GM results in patients on nutritional
      supplements. 

PMID- 24567894
TI  - Cryptococcal infection in non-HIV immunosuppressed patients - Three case reports
      in a nephrology setting.
AB  - Cryptococcal infection has been increasing among immunosuppressed population. We
      report three cases of Cryptococcus neoformans infection in immunosuppressed
      patients - two renal transplanted and one with lupus nephritis. Early infection
      (<3months) was diagnosed in two - an allograft Cryptococcus infection and a
      central nervous system involvement. The third, a 10-year transplant vintage
      patient, presented with cryptococcal meningitis. Amphotericin B provided good
      clinical outcomes. We outline the importance of suspicion for cryptococcal
      infection in immunosuppressed patients. 

PMID- 24567895
TI  - Cerebral macroabscess caused by Candida albicans in an immunocompetent patient: A
      diagnostic challenge.
AB  - We describe the history of a 24-year-old immunocompetent man with an expansive
      lesion in the brainstem that, after many misdiagnoses, was found to be caused by
      a Candida albicans abscess. One year after surgery and 3 months of fluconazole
      treatment, the patient was asymptomatic and all image and laboratory tests were
      normal. 

PMID- 24567896
TI  - First imported coccidioidomycosis in Turkey: A potential health risk for
      laboratory workers outside endemic areas.
AB  - Coccidioidomycosis caused by Coccidioides immitis or Coccidioides posadasii is
      endemic in arid climate zones in America, travel-related cases have been
      reported. We report the first documented case of coccidioidomycosis in Turkey,
      overviewing reported cases in Europe and underlying difficulties of differential
      diagnosis outside endemic regions. The patient was an otherwise healthy 41-year
      old man who travelled endemic areas. Laboratory diagnosis was based on direct
      microscopy of two subsequent subcutaneous biopsy specimens and culture and
      confirmed molecularly. Laboratory personnel should become aware that BioSafety
      Level-3 organisms may become more frequent and widespread. 

PMID- 24567897
TI  - Histoplasmosis outbreak in Tamboril cave-Minas Gerais state, Brazil.
AB  - In this study, we report four cases of Histoplasma capsulatum infection in eight
      biologists who made an expedition to determine the prevalence of this fungus in a
      cave localized in the northwest of Minas Gerais state, Brazil. This case report
      demonstrates the importance of evaluating the H. capsulatum presence in Brazilian
      caves before opening to public visitations. 

PMID- 24567898
TI  - Tuning in to the rhythm of clock genes in skeletal muscle.

PMID- 24567899
TI  - FGF19: How gut talks to brain to keep your sugar down.

PMID- 24567901
TI  - Central action of FGF19 reduces hypothalamic AGRP/NPY neuron activity and
      improves glucose metabolism.
AB  - Tight control of glucose excursions has been a long-standing goal of treatment
      for patients with type 2 diabetes mellitus in order to ameliorate the morbidity
      and mortality associated with hyperglycemia. Fibroblast growth factor (FGF) 19 is
      a hormone-like enterokine released postprandially that emerged as a potential
      therapeutic agent for metabolic disorders, including diabetes and obesity.
      Remarkably, FGF19 treatment has hypoglycemic actions that remain potent in models
      of genetic and acquired insulin resistance. Here, we provided evidence that the
      central nervous system responds to FGF19 administered in the periphery. Then, in
      two mouse models of insulin resistance, leptin-deficiency and high-fat diet
      feeding, third intra-cerebro-ventricular infusions of FGF19 improved glycemic
      status, reduced insulin resistance and potentiated insulin signaling in the
      periphery. In addition, our study highlights a new mechanism of central FGF19
      action, involving the suppression of AGRP/NPY neuronal activity. Overall, our
      work unveils novel regulatory pathways induced by FGF19 that will be useful in
      the design of novel strategies to control diabetes in obesity. 

PMID- 24567900
TI  - SIRT1 metabolic actions: Integrating recent advances from mouse models.
AB  - SIRT1 has attracted a lot of interest since it was discovered as a mammalian
      homolog of Sir2, a protein that influences longevity in yeast. Intensive early
      research suggested a key role of SIRT1 in mammalian development, metabolic
      flexibility and oxidative metabolism. However, it is the growing body of
      transgenic models that are allowing us to clearly define the true range of SIRT1
      actions. In this review we aim to summarize the most recent lessons that
      transgenic animal models have taught us about the role of SIRT1 in mammalian
      metabolic homeostasis and lifespan. 

PMID- 24567902
TI  - Muscle insulin sensitivity and glucose metabolism are controlled by the intrinsic
      muscle clock.
AB  - Circadian rhythms control metabolism and energy homeostasis, but the role of the
      skeletal muscle clock has never been explored. We generated conditional and
      inducible mouse lines with muscle-specific ablation of the core clock gene Bmal1.
      Skeletal muscles from these mice showed impaired insulin-stimulated glucose
      uptake with reduced protein levels of GLUT4, the insulin-dependent glucose
      transporter, and TBC1D1, a Rab-GTPase involved in GLUT4 translocation. Pyruvate
      dehydrogenase (PDH) activity was also reduced due to altered expression of
      circadian genes Pdk4 and Pdp1, coding for PDH kinase and phosphatase,
      respectively. PDH inhibition leads to reduced glucose oxidation and diversion of
      glycolytic intermediates to alternative metabolic pathways, as revealed by
      metabolome analysis. The impaired glucose metabolism induced by muscle-specific
      Bmal1 knockout suggests that a major physiological role of the muscle clock is to
      prepare for the transition from the rest/fasting phase to the active/feeding
      phase, when glucose becomes the predominant fuel for skeletal muscle. 

PMID- 24567903
TI  - Metabolic and transcriptional response to a high-fat diet in Drosophila
      melanogaster.
AB  - Obesity has dramatically increased in prevalence, making it essential to
      understand its accompanying metabolic changes. Modeling diet-induced obesity in
      Drosophila melanogaster (fruit flies), we elucidated transcriptional and
      metabolic changes in w (1118) flies on a high-fat diet (HFD). Mass spectrometry
      based metabolomics revealed altered fatty acid, amino acid, and carbohydrate
      metabolism with HFD. Microarray analysis uncovered transcriptional changes in
      nitrogen metabolism, including CG9510, homolog of human argininosuccinate lyase
      (ASL). CG9510 knockdown in flies phenocopied traits observed with HFD, namely
      increased triglyceride levels and decreased cold tolerance. Restoration of CG9510
      expression ameliorated observed negative consequences of HFD. Metabolomic
      analysis of CG9510 knockdown flies confirmed functional similarity to ASL,
      regulating the balance of carbon and nitrogen metabolism. In summary, we found
      that HFD suppresses CG9510 expression, a gene required for proper triglyceride
      storage and stress tolerance. These results draw an important link between
      regulation of amino acid metabolism and the response to diet-induced obesity. 

PMID- 24567904
TI  - Irs2 and Irs4 synergize in non-LepRb neurons to control energy balance and
      glucose homeostasis.
AB  - Insulin receptor substrates (Irs1, 2, 3 and Irs4) mediate the actions of
      insulin/IGF1 signaling. They have similar structure, but distinctly regulate
      development, growth, and metabolic homeostasis. Irs2 contributes to central
      metabolic sensing, partially by acting in leptin receptor (LepRb)-expressing
      neurons. Although Irs4 is largely restricted to the hypothalamus, its
      contribution to metabolic regulation is unclear because Irs4-null mice barely
      distinguishable from controls. We postulated that Irs2 and Irs4 synergize and
      complement each other in the brain. To examine this possibility, we investigated
      the metabolism of whole body Irs4(-/y) mice that lacked Irs2 in the CNS (bIrs2(-/
      ).Irs4(-/y)) or only in LepRb-neurons (Lepr (?Irs2) .Irs4 (-/y) ). bIrs2(-/
      ).Irs4(-/y) mice developed severe obesity and decreased energy expenditure, along
      with hyperglycemia and insulin resistance. Unexpectedly, the body weight and fed
      blood glucose levels of Lepr (?Irs2) .Irs4 (-/y) mice were not different from
      Lepr (?Irs2) mice, suggesting that the functions of Irs2 and Irs4 converge upon
      neurons that are distinct from those expressing LepRb. 

PMID- 24567906
TI  - The reward value of sucrose in leptin-deficient obese mice.
AB  - Leptin-deficient patients report higher "liking" ratings for food, and leptin
      replacement therapy normalizes these ratings even before weight loss is achieved.
      Since animals cannot report their ratings, we studied the relationship between
      leptin and food reward in leptin-deficient ob/ob mice using a optogenetic assay
      that quantifies the reward value of sucrose. In this assay, mice chose between
      one sipper dispensing the artificial sweetener sucralose coupled to optogenetic
      activation of dopaminergic (DA) neurons, and another sipper dispensing sucrose.
      We found that the reward value of sucrose was high under a state of leptin
      deficiency, as well as at a dose of leptin that does not suppress food intake
      (12.5 ng/h). Treatment with higher doses of leptin decreased the reward value of
      sucrose before weight loss was achieved (100 ng/h), as seen in leptin-deficient
      patients. These results phenocopy in mice the behavior of leptin-deficient
      patients. 

PMID- 24567905
TI  - Arcuate AgRP neurons mediate orexigenic and glucoregulatory actions of ghrelin.
AB  - The hormone ghrelin stimulates eating and helps maintain blood glucose upon
      caloric restriction. While previous studies have demonstrated that hypothalamic
      arcuate AgRP neurons are targets of ghrelin, the overall relevance of ghrelin
      signaling within intact AgRP neurons is unclear. Here, we tested the functional
      significance of ghrelin action on AgRP neurons using a new, tamoxifen-inducible
      AgRP-CreER(T2) transgenic mouse model that allows spatiotemporally-controlled re
      expression of physiological levels of ghrelin receptors (GHSRs) specifically in
      AgRP neurons of adult GHSR-null mice that otherwise lack GHSR expression. AgRP
      neuron-selective GHSR re-expression partially restored the orexigenic response to
      administered ghrelin and fully restored the lowered blood glucose levels observed
      upon caloric restriction. The normalizing glucoregulatory effect of AgRP neuron
      selective GHSR expression was linked to glucagon rises and hepatic
      gluconeogenesis induction. Thus, our data indicate that GHSR-containing AgRP
      neurons are not solely responsible for ghrelin's orexigenic effects but are
      sufficient to mediate ghrelin's effects on glycemia. 

PMID- 24567908
TI  - Accurate GM atrophy quantification in MS using lesion-filling with co-registered
      2D lesion masks.
AB  - BACKGROUND: In multiple sclerosis (MS), brain atrophy quantification is affected
      by white matter lesions. LEAP and FSL-lesion_filling, replace lesion voxels with
      white matter intensities; however, they require precise lesion identification on
      3DT1-images. AIM: To determine whether 2DT2 lesion masks co-registered to 3DT1
      images, yield grey and white matter volumes comparable to precise lesion masks.
      METHODS: 2DT2 lesion masks were linearly co-registered to 20 3DT1-images of MS
      patients, with nearest-neighbor (NNI), and tri-linear interpolation. As gold
      standard, lesion masks were manually outlined on 3DT1-images. LEAP and FSL
      lesion_filling were applied with each lesion mask. Grey (GM) and white matter
      (WM) volumes were quantified with FSL-FAST, and deep gray matter (DGM) volumes
      using FSL-FIRST. Volumes were compared between lesion mask types using paired
      Wilcoxon tests. RESULTS: Lesion-filling with gold-standard lesion masks compared
      to native images reduced GM overestimation by 1.93 mL (p < .001) for LEAP, and
      1.21 mL (p = .002) for FSL-lesion_filling. Similar effects were achieved with NNI
      lesion masks from 2DT2. Global WM underestimation was not significantly
      influenced. GM and WM volumes from NNI, did not differ significantly from gold
      standard. GM segmentation differed between lesion masks in the lesion area, and
      also elsewhere. Using the gold-standard, FSL-FAST quantified as GM on average
      0.4% of the lesion area with LEAP and 24.5% with FSL-lesion_filling. Lesion
      filling did not influence DGM volumes from FSL-FIRST. DISCUSSION: These results
      demonstrate that for global GM volumetry, precise lesion masks on 3DT1 images can
      be replaced by co-registered 2DT2 lesion masks. This makes lesion-filling a
      feasible method for GM atrophy measurements in MS.

PMID- 24567907
TI  - Dysconnectivity of neurocognitive networks at rest in very-preterm born adults.
AB  - Advances in neonatal medicine have resulted in a larger proportion of preterm
      born individuals reaching adulthood. Their increased liability to psychiatric
      illness and impairments of cognition and behaviour intimate lasting cerebral
      consequences; however, the central physiological disturbances remain unclear. Of
      fundamental importance to efficient brain function is the coordination and
      contextually-relevant recruitment of neural networks. Large-scale distributed
      networks emerge perinatally and increase in hierarchical complexity through
      development. Preterm-born individuals exhibit systematic reductions in
      correlation strength within these networks during infancy. Here, we investigate
      resting-state functional connectivity in functional magnetic resonance imaging
      data from 29 very-preterm (VPT)-born adults and 23 term-born controls.
      Neurocognitive networks were identified with spatial independent component
      analysis conducted using the Infomax algorithm and employing Icasso procedures to
      enhance component robustness. Network spatial focus and spectral power were not
      generally significantly affected by preterm birth. By contrast, Granger-causality
      analysis of the time courses of network activity revealed widespread reductions
      in between-network connectivity in the preterm group, particularly along paths
      including salience-network features. The potential clinical relevance of these
      Granger-causal measurements was suggested by linear discriminant analysis of
      topological representations of connection strength, which classified individuals
      by group with a maximal accuracy of 86%. Functional connections from the striatal
      salience network to the posterior default mode network informed this
      classification most powerfully. In the VPT-born group it was additionally found
      that perinatal factors significantly moderated the relationship between executive
      function (which was reduced in the VPT-born as compared with the term-born group)
      and generalised partial directed coherence. Together these findings show that
      resting-state functional connectivity of preterm-born individuals remains
      compromised in adulthood; and present consistent evidence that the striatal
      salience network is preferentially affected. Therapeutic practices directed at
      strengthening within-network cohesion and fine-tuning between-network inter
      relations may have the potential to mitigate the cognitive, behavioural and
      psychiatric repercussions of preterm birth. 

PMID- 24567909
TI  - Altered functional connectivity of the language network in ASD: role of classical
      language areas and cerebellum.
AB  - The development of language, social interaction and communicative skills is
      remarkably different in the child with autism spectrum disorder (ASD). Atypical
      brain connectivity has frequently been reported in this patient population.
      However, the neural correlates underlying their disrupted language development
      and functioning are still poorly understood. Using resting state fMRI, we
      investigated the functional connectivity properties of the language network in a
      group of ASD patients with clear comorbid language impairment (ASD-LI; N = 19)
      and compared them to the language related connectivity properties of 23 age
      matched typically developing children. A verb generation task was used to
      determine language components commonly active in both groups. Eight joint
      language components were identified and subsequently used as seeds in a resting
      state analysis. Interestingly, both the interregional and the seed-based whole
      brain connectivity analysis showed preserved connectivity between the classical
      intrahemispheric language centers, Wernicke's and Broca's areas. In contrast
      however, a marked loss of functional connectivity was found between the right
      cerebellar region and the supratentorial regulatory language areas. Also, the
      connectivity between the interhemispheric Broca regions and modulatory control
      dorsolateral prefrontal region was found to be decreased. This disruption of
      normal modulatory control and automation function by the cerebellum may underlie
      the abnormal language function in children with ASD-LI. 

PMID- 24567910
TI  - Brain putamen volume changes in newly-diagnosed patients with obstructive sleep
      apnea.
AB  - Obstructive sleep apnea (OSA) is accompanied by cognitive, motor, autonomic,
      learning, and affective abnormalities. The putamen serves several of these
      functions, especially motor and autonomic behaviors, but whether global and
      specific sub-regions of that structure are damaged is unclear. We assessed global
      and regional putamen volumes in 43 recently-diagnosed, treatment-naive OSA (age,
      46.4 +/- 8.8 years; 31 male) and 61 control subjects (47.6 +/- 8.8 years; 39
      male) using high-resolution T1-weighted images collected with a 3.0-Tesla MRI
      scanner. Global putamen volumes were calculated, and group differences evaluated
      with independent samples t-tests, as well as with analysis of covariance
      (covariates; age, gender, and total intracranial volume). Regional differences
      between groups were visualized with 3D surface morphometry-based group ratio
      maps. OSA subjects showed significantly higher global putamen volumes, relative
      to controls. Regional analyses showed putamen areas with increased and decreased
      tissue volumes in OSA relative to control subjects, including increases in
      caudal, mid-dorsal, mid-ventral portions, and ventral regions, while areas with
      decreased volumes appeared in rostral, mid-dorsal, medial-caudal, and mid-ventral
      sites. Global putamen volumes were significantly higher in the OSA subjects, but
      local sites showed both higher and lower volumes. The appearance of localized
      volume alterations points to differential hypoxic or perfusion action on glia and
      other tissues within the structure, and may reflect a stage in progression of
      injury in these newly-diagnosed patients toward the overall volume loss found in
      patients with chronic OSA. The regional changes may underlie some of the specific
      deficits in motor, autonomic, and neuropsychologic functions in OSA. 

PMID- 24567912
TI  - Graph theoretical analysis indicates cognitive impairment in MS stems from neural
      disconnection.
AB  - BACKGROUND: The mechanisms underlying cognitive impairment in MS are still poorly
      understood. However, due to the specific pathology of MS, one can expect
      alterations in connectivity leading to physical and cognitive impairment. AIM: In
      this study we aimed at assessing connectivity differences in EEG between
      cognitively impaired (CI) and cognitively preserved (CP) MS patients. We also
      investigated the influence of the measures used to construct networks. METHODS:
      We included 308 MS patients and divided them into two groups based on their
      cognitive score. Graph theoretical network analyses were conducted based on
      networks constructed using different connectivity measures, i.e. correlation,
      correlation in the frequency domain, coherence, partial correlation, the phase
      lag index and the imaginary part of coherency. The most commonly encountered
      network parameters were calculated and compared between the two groups using
      Wilcoxon's rank test. Clustering coefficients and path lengths were normalized to
      a randomized mean clustering coefficient and path length for each patient. False
      discovery rate was used to correct for the multiple comparisons and Cohen's d
      effect sizes are reported. RESULTS: Coherence analysis suggests that theta and
      delta connectivity is significantly smaller in cognitively impaired patients.
      Small-worldness differences are found in networks based on correlation, theta and
      delta coherence and correlation in the frequency domain. Modularity was related
      to age but not to cognition. CONCLUSION: Cognitive deterioration in MS is a
      symptom that seems to be caused by neural disconnections, probably the white
      matter tracts connecting both hemispheres, and leads to a wide range in network
      differences which can be assessed by applying GTA to EEG data. In the future,
      these results may lead to cheaper and more objective assessments of cognitive
      impairment in MS.

PMID- 24567911
TI  - Disrupted working memory circuitry and psychotic symptoms in 22q11.2 deletion
      syndrome.
AB  - 22q11.2 deletion syndrome (22q11DS) is a recurrent genetic mutation that is
      highly penetrant for psychosis. Behavioral research suggests that 22q11DS
      patients exhibit a characteristic neurocognitive phenotype that includes
      differential impairment in spatial working memory (WM). Notably, spatial WM has
      also been proposed as an endophenotype for idiopathic psychotic disorder, yet
      little is known about the neurobiological substrates of WM in 22q11DS. In order
      to investigate the neural systems engaged during spatial WM in 22q11DS patients,
      we collected functional magnetic resonance imaging (fMRI) data while 41
      participants (16 22q11DS patients, 25 demographically matched controls) performed
      a spatial capacity WM task that included manipulations of delay length and load
      level. Relative to controls, 22q11DS patients showed reduced neural activation
      during task performance in the intraparietal sulcus (IPS) and superior frontal
      sulcus (SFS). In addition, the typical increases in neural activity within
      spatial WM-relevant regions with greater memory load were not observed in
      22q11DS. We further investigated whether neural dysfunction during WM was
      associated with behavioral WM performance, assessed via the University of
      Maryland letter-number sequencing (LNS) task, and positive psychotic symptoms,
      assessed via the Structured Interview for Prodromal Syndromes (SIPS), in 22q11DS
      patients. WM load activity within IPS and SFS was positively correlated with LNS
      task performance; moreover, WM load activity within IPS was inversely correlated
      with the severity of unusual thought content and delusional ideas, indicating
      that decreased recruitment of working memory-associated neural circuitry is
      associated with more severe positive symptoms. These results suggest that 22q11DS
      patients show reduced neural recruitment of brain regions critical for spatial WM
      function, which may be related to characteristic behavioral manifestations of the
      disorder. 

PMID- 24567913
TI  - Immunological-based assays for specific detection of shrimp viruses.
AB  - Among shrimp viral pathogens, white spot syndrome virus (WSSV) and yellow head
      virus (YHV) are the most lethal agents, causing serious problems for both the
      whiteleg shrimp, Penaeus (Litopenaeus) vannamei, and the black tiger shrimp,
      Penaeus (Penaeus) monodon. Another important virus that infects P. vannamei is
      infectious myonecrosis virus (IMNV), which induces the white discoloration of
      affected muscle. In the cases of taura syndrome virus and Penaeus stylirostris
      densovirus (PstDNV; formerly known as infectious hypodermal and hematopoietic
      necrosis virus), their impacts were greatly diminished after the introduction of
      tolerant stocks of P. vannamei. Less important viruses are Penaeus monodon
      densovirus (PmDNV; formerly called hepatopancreatic parvovirus), and Penaeus
      monodon nucleopolyhedrovirus (PemoNPV; previously called monodon baculovirus).
      For freshwater prawn, Macrobrachium rosenbergii nodavirus and extra small virus
      are considered important viral pathogens. Monoclonal antibodies (MAbs) specific
      to the shrimp viruses described above have been generated and used as an
      alternative tool in various immunoassays such as enzyme-linked immunosorbent
      assay, dot blotting, Western blotting and immunohistochemistry. Some of these
      MAbs were further developed into immunochromatographic strip tests for the
      detection of WSSV, YHV, IMNV and PemoNPV and into a dual strip test for the
      simultaneous detection of WSSV/YHV. The strip test has the advantages of speed,
      as the result can be obtained within 15 min, and simplicity, as laboratory
      equipment and specialized skills are not required. Therefore, strip tests can be
      used by shrimp farmers for the pond-side monitoring of viral infection. 

PMID- 24567916
TI  - Ultrasound for everyone - is it the right time?

PMID- 24567915
TI  - Heterotypic cellular interactions in the ovarian tumor microenvironment:
      biological significance and therapeutic implications.
AB  - The majority of women who are diagnosed with epithelial ovarian cancer present
      with extensive peritoneal carcinomatosis and are rarely cured by conventional
      chemotherapy. Ovarian cancer cells typically disseminate by shedding into the
      peritoneal fluid and implant on the mesothelium-lined peritoneal surfaces that
      overlie connective and white adipose tissues. Emerging evidence indicates that
      ovarian tumor progression is orchestrated by dynamic interplay between tumor
      cells and a variety of stromal cells such as adipocytes, endothelial cells,
      fibroblasts, mesenchymal stem cells, macrophages, and other immune cells. This
      mini-review discusses the biological significance of the heterotypic cellular
      interactions in the ovarian tumor microenvironment and the therapeutic
      implications of targeting these interactions. 

PMID- 24567917
TI  - Contrast-enhanced ultrasound of lymph nodes: towards better imaging.

PMID- 24567918
TI  - The place of CEUS in distinguishing benign from malignant cervical lymph nodes: a
      prospective study.
AB  - AIMS: The aim of the study was to evaluate the ability of contrast-enhanced
      ultrasonography (CEUS) compared to gray-scale B-mode and color Doppler ultrasound
      in differentiate benign versus malign superficial cervical lymph nodes. MATERIAL
      AND METHODS: In a prospective study ultrasonography (gray scale, color and
      spectral Dopller, and CEUS) was performed in 61 patients (33 men, 28 women; mean
      age of 51.2 years, range: 18-81 years), with cervical lymphadenopathy. The nodes
      were examined and biopsied or surgically removed. CEUS was performed with 2.4 ml
      intravenous bolus of contrast agent Sono Vue and the results were registered with
      a special software. RESULTS: Of all the nodes, 32 were benign and 29 were
      malignant (metastases). Solbiati index was higher in benign nodes (2.23 +/- 0.84
      vs 1.50 +/- 0.48, p<0.05). Doppler parameters (vessel location, vascular pattern,
      pedicullum number, resistivity index, and pulsatility index) were significantly
      lower in benign nodes (p<0.001), and ROC analysis returned excellent results. For
      CEUS, derived peak intensity (DPI %) was higher in benign nodes (17.72 +/- 5.43
      vs 11.76 +/- 4.88, p<0.05); regional blood volume (RBV) was also higher (849.8 +/
      467.1 vs 458.3 +/- 283.3, p<0.05). The time to peak (TTP, s) and area under the
      curve (AUC, cm2) were similar in both benign and malignant nodes. Enhancement
      pattern was the most accurate to characterize benign versus malignant nodes.
      Sensitivity and specificity were higher for DPI, RBV and enhancement pattern from
      CEUS, according to ROC analysis, compared to gray scale ultrasound, but lower
      than color Doppler. Analyzing the place of CEUS in lymph node evaluation we found
      that CEUS is most useful for the evaluation of the lymph nodes with uncertain
      aspect at gray scale and Doppler evaluation. CONCLUSIONS: ROC analysis confirmed
      the higher degree of diagnostic accuracy of CEUS in comparison with conventional
      techniques for some parameters such as enhancement pattern. Evaluation of nodal
      perfusion with this method can be helpful in the differentiation of benign from
      malignant nodes but requires further confirmation.

PMID- 24567914
TI  - Regulation of Mouse Retroelement MuERV-L/MERVL Expression by REX1 and Epigenetic
      Control of Stem Cell Potency.
AB  - About half of the mammalian genome is occupied by DNA sequences that originate
      from transposable elements. Retrotransposons can modulate gene expression in
      different ways and, particularly retrotransposon-derived long terminal repeats,
      profoundly shape expression of both surrounding and distant genomic loci. This is
      especially important in pre-implantation development, during which extensive
      reprograming of the genome takes place and cells pass through totipotent and
      pluripotent states. At this stage, the main mechanism responsible for
      retrotransposon silencing, i.e., DNA methylation, is inoperative. A particular
      retrotransposon called muERV-L/MERVL is expressed during pre-implantation stages
      and contributes to the plasticity of mouse embryonic stem cells. This review will
      focus on the role of MERVL-derived sequences as controlling elements of gene
      expression specific for pre-implantation development, two-cell stage-specific
      gene expression, and stem cell pluripotency, the epigenetic mechanisms that
      control their expression, and the contributions of the pluripotency marker REX1
      and the related Yin Yang 1 family of transcription factors to this regulation
      process. 

PMID- 24567919
TI  - Abnormal sonographic appearances of the yolk sac: which can be associated with
      adverse perinatal outcome?
AB  - AIMS: The present study aimed to determine whether yolk sacs with abnormal
      sonographic appearance are associated with adverse perinatal outcomes in both
      early and late gestation. MATERIAL AND METHODS: A total of 305 viable singleton
      pregnancies with gestational age of 6 to 9 weeks were prospectively evaluated
      with respect to perinatal outcomes and sonographic characteristics of the yolk
      sacs. RESULTS: An abnormal yolk sac was found in 66 pregnancies. In pregnancies
      with enlarged yolk sacs a miscarriage occurred in 37.5% of cases (3/8). The
      pregnancies with a yolk sac diameter >/= 5 mm had a significantly higher risk of
      miscarriage (p = 0.005). The risk of miscarriage was statistically similar
      between the pregnancies with regular and those with irregular yolk sacs (p =
      0.73). Miscarriage occurred in 3.8% of pregnancies with irregular yolk sacs
      (2/52) and none of pregnancies with echogenic yolk sacs (0/6). Adverse perinatal
      outcomes were not associated with either irregular or echogenic yolk sacs.
      CONCLUSIONS: An enlarged yolk sac visualized before the 7th week of gestation is
      strongly associated with a significantly increased risk for spontaneous
      miscarriage. The presence of an echogenic or irregular yolk sac appears to be
      unrelated to adverse perinatal outcome.

PMID- 24567921
TI  - Comparison of a new, modified lung ultrasonography technique with high-resolution
      CT in the diagnosis of the alveolo-interstitial syndrome of systemic scleroderma.
AB  - AIMS: Pulmonary fibrosis is the main cause of mortality in patients with Systemic
      Scleroderma (SSc). This study was performed to investigate the utility of
      modified trans-thoracic ultrasound (TTUS) scoring system according to the comet
      tail sign (B-line artifacts) and to compare it with high-resolution computed
      tomography (HRCT) findings in patients with SSc and pulmonary involvement.
      PATIENTS AND METHOD: Seventy subjects with SSc diagnosed according to the
      American College of Rheumatology criteria were enrolled. All subjects underwent
      HRCT followed by TTUS for comet tail sign detection in order to predict the
      degree of lung fibrosis. The modified TTUS assessment was performed at 10
      intercostals spaces level. RESULTS: A significantly positive correlation between
      TTUS and the severity of pulmonary involvement (Spearman's correlation
      coefficient= 0.695, P < 0.001), (LR=74.36, P<0.001) was found. When compared with
      HRCT as the gold standard method, the sensitivity, specificity, positive and
      negative predictive value of TTUS was 73.58%, 88.23%, 95.12% and 51.72%
      respectively. Kappa values for the intra-observer modified TTUS assessment was
      0.838. CONCLUSIONS: Our study showed that the modified TTUS comet tails scoring
      system could be useful in the assessment of the pulmonary involvement in patients
      with SSc.

PMID- 24567920
TI  - Assessment of pelvic floor of women runners by three-dimensional ultrasonography
      and surface electromyography. A pilot study.
AB  - AIM: To evaluate female runners' pelvic floor muscles using three-dimensional
      ultrasonography (3DUS) and surface electromyography (SEMG). MATERIAL AND METHODS:
      A cross-sectional study was conducted on 24 female runners. SEMG was performed
      using surface electrodes inserted in the vagina. 3DUS was performed using
      perineal convex transducer. SEMG was evaluated at rest and with maximum voluntary
      contraction (MVC) and slow contraction. Levator ani muscle thickness, levator
      hiatus area and the angle between the levator muscles at rest and with MVC and
      Valsalva were evaluated using 3DUS. The women were divided into two groups (women
      running </= 25 km/week; women running > 25 km/week). Means, standard deviations
      and non-paired t tests were used for both groups. RESULTS: Among the 24 women, 11
      ran </= 25 km/week (16.91 +/- 4.13 km/week) and 13 ran > 25 km/week (40.77 +/-
      1.15 km/week). The mean SEMG at rest and with MVC and slow contraction were
      16.25, 65.86 and 71.41 mV, respectively. For the levator hiatus area at rest and
      with MVC and Valsalva, the means were 12.54, 10.06 and 16.57 sqcm, respectively.
      Correlations between 3DUS and SEMG showed significant differences in SEMG at rest
      and levator thickness with Valsalva (r = 0.46; p = 0.04). CONCLUSIONS: 3DUS and
      SEMG are two feasible methods for evaluating female runners' pelvic floor.
      Correlations between 3DUS and SEMG showed significant differences in SEMG at rest
      and levator thickness with Valsalva.

PMID- 24567923
TI  - Is Contrast Enhanced Ultrasound (CEUS) ready for use in daily practice for
      evaluation of focal liver lesions?
AB  - Abdominal ultrasound is one of the most popular imaging methods due to its
      feasibility, low cost and accessibility. Contrast Enhanced Ultrasound (CEUS) with
      second generation contrast agents became in the last years a useful tool for the
      characterization of focal liver lesions (FLL) so that EFSUMB issued guidelines
      for its use in clinical practice. Several large studies proved that CEUS has
      similar performance to more expensive imaging methods such as contrast enhanced
      CT and contrast enhanced MRI for the characterization of FLL. Also, several
      studies proved that CEUS is cost-effective as a first-line imaging method.
      Considering all these data, we think that CEUS is ready to be used in daily
      practice for the evaluation of FLL. 

PMID- 24567922
TI  - Inter & intra-observer reliability of grading ultrasound videoclips with hand
      pathology in rheumatoid arthritis by using non- sophisticated internet tools
      (LUMINA study).
AB  - AIM: To evaluate the inter- and intraobserver agreement of a group of European
      rheumatologist ultrasonographers in grading musculoskeletal ultrasound videoclips
      posted on the Internet by using a non-sophisticated electronic environment.
      METHODS: Forty short movie clips (less than 30 secs) were made available over the
      Internet to all participants. Normal and pathological RA hand joints and tendons
      were included in the movie clips. In the first phase 30 investigators from
      European countries were invited to evaluate the clips and to interpret/grade
      them. No instruction session was held prior to the initiation of the study. For
      synovitis the requested scoring system included 0 to3 grades and for
      tenosynovitis a binary variable 0/1; separate evaluations were performed for gray
      scale (GS) and Power Doppler (PD) examinations. In the second phase the
      responders were asked to grade the same clips in a different order without having
      access to their first grading scale. Light's k and Cohen's k were used to analyse
      inter- and intraobserver reliability. RESULTS: Twenty two European
      rheumatologists agreed to finalise both study phases. Mean Cohen's kappa for
      intraobserver reliability was 0.614/0.689 for tenosynovitis GS/PD and 0.523/0.621
      for synovitis GS/PD. Light's k for interobserver reliability was 0.503 for
      tenosynovitis evaluation and 0.455 for global (synovitis and tenosynovitis)
      evaluation. Mean global overall agreement was 84.95% (90.2% for global
      synovitis). CONCLUSIONS: An over-the-net US evaluation and grading has shown
      moderate to good reliability. The results could be improved if a training session
      is added at the beginning of the study.

PMID- 24567924
TI  - Role of contrast enhanced ultrasound in the assessment of biliary duct disease.
AB  - The introduction of microbubble contrast agents (CA), which act as blood pool
      tracers, has overcome the limitations of conventional B-Mode, colour or power
      Doppler ultrasound, enabling the display of parenchymal microvasculature.
      Initially, the use of CA was accepted for hepatic lesions. In the following
      years, experts have expanded recommendations, as a result of the method's
      efficiency in extrahepatic applications. In this article we review the
      methodology and the application of contrast-enhanced ultrasound (CEUS) in the
      evaluation of biliary pathology. This new imaging tool allows a non invasive
      differential diagnosis of biliary lesions and a clearer delineation of the
      tumoral process. 

PMID- 24567925
TI  - Ultrasonography of the spleen. Pictorial essay.
AB  - Contrast-enhanced ultrasound is widely indicated in the study of splenic
      diseases, especially due to its good specificity in the differentiation of benign
      from malignant splenic lesions. The purpose of this pictorial essay is to offer a
      review of the most common splenic pathologies, while illustrating them with
      sonographic images. 

PMID- 24567926
TI  - A rare anatomical variation of the greater saphenous vein. Case report.
AB  - The venous system has frequent anatomical variations. A good understanding of the
      venous anatomy is very important and proper evaluation of the venous system is
      crucial for the appropriate treatment of venous disorders. There are many
      variations of the greater saphenous vein at the level of the thigh, knee and leg.
      All variations of the saphenofemoral junction reported in the literature refer to
      the drainage of the greater saphenous vein into the common femoral vein. A very
      rare greater saphenous vein variation at the level of the saphenofemoral junction
      is defined and discussed in this case report. 

PMID- 24567927
TI  - Cardiac amyloidosis evaluation by bedside ultrasound in the emergency department.
      A case report.
AB  - Cardiac amyloidosis is a disease process of abnormal amyloid fibril deposition in
      cardiac muscle that can be diagnosed by specific electrocardiographic and
      echocardiographic findings. We present the case of a patient with a history of
      cardiac amyloidosis who presented to the emergency department (ED) with shortness
      of breath, and was diagnosed with a large pericardial effusion by
      ultrasonography. The patient's myocardium exhibited a granular, "sparkling"
      appearance with increased echogenicity, typical for cardiac amyloidosis. We
      discuss the bedside ultrasound findings found in this infiltrative
      cardiomyopathy, and how they influenced the ED management and treatment plan for
      this patient. 

PMID- 24567928
TI  - Role of ultrasonography with color-Doppler in the emergency diagnosis of acute
      penile fracture: a case report.
AB  - Penile fracture is the rupture of tunica albuginea, typically resulting from
      blunt trauma, intercourse, or penile manipulation. Diagnosis is made clinically.
      Ultrasound is not used frequently in diagnosis of penile fracture but it provides
      a fast, non-invasive alternative to more often used MRI and cavernography. We
      aimed to present diagnostic ultrasound and color Doppler images of a patient with
      acute penile fracture in conjunction with literature. 

PMID- 24567929
TI  - An atypical case of focal nodular hyperplasia. Problems of imagistic diagnosis.
AB  - Focal nodular hyperplasia (FNH) is a hepatic disease first described in 1958. The
      existence of an accessible and minimally invasive imagistic investigation to
      establish the diagnosis in a large number of cases would be desirable, especially
      because once diagnosed, the disease needs no treatment. We present the case of a
      young woman with long term use of oral contraceptives in which the diagnosis of
      FNH was established at a routine ultrasound. Evolution of disease during the
      pregnancy and the atypical imagistic aspect of liver lesions raised many problems
      of differential diagnosis. 

PMID- 24567930
TI  - Subclavian fusiform aneurysm causing partial subclavian steal syndrome. Case
      report.
AB  - We present a 55-year-old man with repeated transient symptoms of vertebrobasilar
      arterial pathology. Physical examination detected no signs that would indicate
      the stenosis of the proximal subclavian artery segment. Ultrasound detected
      hemodynamic disorder of right vertebral artery, which correspond to a partial
      subclavian steal syndrome. Angiography shows fusiform aneurysm of ipsilateral
      subclavian artery in which central part is the base of hypoplastic vertebral
      artery. In the literature are rare reports of cases of partial subclavian steal
      syndrome caused by aneurysmal expansion of subclavian artery. 

PMID- 24567931
TI  - Ultrasound based techniques and transient elastography may not be precise methods
      for the detection of esophageal varices in liver cirrhosis.

PMID- 24567932
TI  - Contrast enhanced ultrasound and magnetic resonance imaging for hepatoma
      diagnosis.

PMID- 24567934
TI  - No Relationship between Serum and Salivary beta2- Microglobulin Levels in A
      Sample of Adult Diabetic Men with Chronic Kidney Disease without Renal
      Replacement Therapy.
AB  - OBJECTIVE: Beta2-microglobulin (beta2M) associated amyloidosis is an inevitable
      complication of chronic kidney disease (CKD). Testing beta2M in the blood is
      invasive and expensive. On the other hand, oral fluid is a perfect medium to be
      explored for public health and disease surveillance. However, it has never been
      studied if salivary concentration of beta2M reflects its concentration in the
      serum. The current study; therefore, aimed to examine the relationship between
      salivary and serum beta2M in a sample of adult diabetic men with CKD. MATERIALS
      AND METHODS: Among diabetic patients referred to the Nephrology Department of The
      Golestan Hospital of Ahvaz due to CKD, 40 men not requiring renal replacement
      therapy were consecutively recruited for this cross-sectional study. Patients
      were excluded if they had any disease or were using any drugs that might affect
      the oral mucosa or saliva. The concentration of beta2M was measured in both serum
      and saliva. The correlation between serum and salivary beta2M was measured by
      calculating spearman's rho. RESULTS: The Spearman's rho for correlation between
      serum and salivary beta2M was -0.017 (p=0.917), indicating lack of correlation.
      Serum and salivary creatinine (Spearman's rho=0.54; p value<0.001) as well as
      serum and salivary urea nitrogen levels (Spearman's rho=0.39; p value=0.014) were
      correlated. CONCLUSION: Salivary beta2M levels poorly agreed with serum beta2M
      levels, and thus may not be used as a surrogate for serum beta2M in CKD patients
      who did not require replacement therapy.

PMID- 24567933
TI  - Association of Chromosomal Translocation and MiRNA Expression with The
      Pathogenesis of Multiple Myeloma.
AB  - Multiple myeloma (MM), is the second most common blood cancer after non-Hodgkin's
      lymphoma. Genetic changes, structural and numerical chromosome anomalies, are
      involved in pathogenesis of MM, and are among the most important prognostic
      factors of disease-associated patient survival. MicroRNAs (miRNAs) are small 19
      22 nucleotide single-stranded RNAs involved in important cellular processes.
      Cytogenetic changes in plasma cells alter miRNA expression and function. MiRNAs
      act as tumor suppressors and oncogenes by affecting intracellular signaling
      pathways. MiRNA expression is associated with a specific genetic change and may
      assist with diagnosis and disease prognosis. This study aims to evaluate recent
      findings in MM-associated cytogenetic changes and their relationship with changes
      in the expression of miRNAs. We have determined that MM-associated cytogenetic
      changes are related to changes in the expression of miRNAs and CD markers
      (cluster of differentiation) are associated with disease survival. Information
      about these changes can be used for therapeutic purposes and disease prognosis. 

PMID- 24567935
TI  - The effects of exendine-4 on insulin producing cell differentiation from rat bone
      marrow-derived mesenchymal stem cells.
AB  - OBJECTIVE: The aim of this study was to evaluate the effect of exendin-4 (EX-4)
      on differentiation of insulin-producing cells (IPCs) from rat bone marrow-derived
      mesenchymal stem cells (RAT-BM-MSCs). MATERIALS AND METHODS: In this experimental
      study, RAT-BM-MSCs were cultured and the cells characterized by flow cytometry
      analysis of cell surface markers. RAT-BM-MSCs were subsequently treated with
      induction media with or without EX-4. After induction, the presence of IPCs was
      demonstrated with dithizone (DTZ) staining and gene expression profiles for
      pancreatic cell differentiation markers (PDX-1, GLUT-2, insulin) were assessed
      using reverse transcription polymerase chain reaction (RT-PCR). Insulin excreted
      from differentiated cells was analyzed with radioimmunoassay (RIA). The two
      tailed student's t-test was used for comparison of the obtained values. RESULTS:
      The percentage of DTZ-positive cells significantly increased in EX-4 treated
      cells (p<0.05). Expression of the islet-associated genes PDX-1, GLUT-2 and
      insulin genes in EX-4 treated cells was markedly higher than in the cells exposed
      to differentiation media without EX-4. RIA analysis demonstrated significant
      release of insulin with the glucose challenge test in EX-4 treated cells compared
      to EX-4 untreated cells. CONCLUSION: The results of this study have demonstrated
      that EX-4 can enhance differentiation of IPCs from RAT-BM-MSCs.

PMID- 24567936
TI  - Cysteine: a novel neural inducer for rat bone marrow mesenchymal stem cells.
AB  - OBJECTIVE: Mesenchymal stem cells (MSCs) can differentiate into various cell
      types. Since cysteine has structural similarities to neuronal inducers beta
      mercaptoethanol and glutathione, we examined its effect on neural induction of
      rat bone marrow MSCs. MATERIALS AND METHODS: In this experimental study, cells
      were treated in a medium containing 1mM cysteine for 24 hours prior to treatment
      with neuron inducing medium containing 10 mM cysteine for 1, 2 and 3 hours. Cell
      viability and morphology were assessed by 3-(4,5-dimethylthiazol-2-Yl)-2,5
      diphenyltetrazolium bromide (MTT) assay and, Hoechst, propidium iodide and
      acridine orange staining respectively. Expression of nestin and beta-Tubulin III
      genes, as neural cell-specific markers, was studied reverse transcription
      polymerase chain reaction (RT-PCR). The data was statistically analyzed using One
      Way ANOVA and Tukey's test and p<0.05 was considered significant. RESULTS: After
      3 hours of treatment, neuron like morphology with a considerable expression of
      nestin and beta-Tubulin III genes was apparent. The mean cell viability was not
      significantly different at 1, 2 and 3 hours following induction, compared with
      the control cells. CONCLUSION: Cysteine can induce neural features in rat bone
      marrow MSCs without reducing cell viability. Therefore, it can be considered as a
      safer alternative to toxic neural inducer agents such as beta-mercaptoethanol.

PMID- 24567937
TI  - Cytotoxic Effect of Immunotoxin Containing The Truncated Form of Pseudomonas
      Exotoxin A and Anti-VEGFR2 on HUVEC and MCF-7 Cell Lines.
AB  - OBJECTIVE: Immunotoxins (ITs) have been developed for the treatment of cancer,
      and comprise of antibodies linked to toxins. Also vascular endothelial growth
      factor (VEGF) plays a key role in tumor angiogenesis, and the blockade of VEGF
      receptor-2 (VEGFR2) inhibits angiogenesis and tumor growth. The aim of this study
      was to produce anti-VEGFR2/rPE (Pseudomonas exotoxin) 38 IT to test its cytotoxic
      activity and mechanism of action. MATERIALS AND METHODS: In this basic research
      and experimental study, at first, DNA that encodes recombinant PE38 protein was
      inductively expressed in Escherichia coli (E.coli) and purified by nickel
      sepharose chromatography and further analyzed by western blot. Then, for
      production of IT, rPE38 was chemically conjugated to anti- VEGFR2. The
      cytotoxicity response of IT treatment was evaluated by 3-(4,5-Dimethylthiazol-2
      Yl)-2,5-Diphenyltetrazolium Bromide (MTT) test in Human Umbilical Vein
      Endothelial Cell (HUVEC) and Michigan Cancer Foundation-7 (MCF-7) (VEGFR2+) cell
      lines. The mechanism of IT cytotoxicity was observed by Annexin V staining and
      flow cytometry. Continuous variables were compared with the analysis of variance
      (ANOVA; for all groups). P values less than 0.05 were considered statistically
      significant. RESULTS: SDS-PAGE showed 98% purity of rPE38 and IT. In vitro dose
      dependent cytotoxicity assay demonstrated that anti-VEGFR2/PE38 is toxic to
      VEGFR2-positive cells. IT treatment significantly inhibited proliferation of
      HUVEC and MCF-7 in a VEGFR2-specific manner as compared with the control groups
      (p<0.05). Flow cytometry showed that the mechanism of IT induced cell death is
      mediated by apoptosis. CONCLUSION: IT treatment also caused remarkable
      synergistic cytotoxicity characterized by decreased cell viability, and an
      increased apoptotic index by both anti-VEGFR2 and PE38. Thus these results raise
      the possibility of using anti-VEGFR2/PE38 IT for cancer therapy because nearly
      all tumors induce local angiogenesis with high VEGFR expression.

PMID- 24567938
TI  - Lack of Association between ESR1 and CYP1A1 Gene Polymorphisms and Susceptibility
      to Uterine Leiomyoma in Female Patients of Iranian Descent.
AB  - Uterine leiomyoma (UL) is the most common benign smooth muscle cell tumor with as
      yet unknown etiology and pathogenesis. This study was carried out to investigate
      the association of ESR1-351 A>G, ESR1 -397 T>C and CYP1A1 (Ile462Val)
      polymorphisms with UL in female patients of Iranian origin. In this case-control
      study, 276 patients with UL and 156 healthy women were recruited. The genetic
      polymorphisms ESR1-351 A>G, ESR1-397 T>C and CYP1A1 (Ile462Val) were genotyped by
      polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP).
      No significant difference were found in frequencies of both genotypes and alleles
      of ESR1-351 A>G, ESR1-397 T>C and CYP1A1 (Ile462Val) polymorphisms between the
      two groups (p>0.05). Our findings indicated that these ESR1 and CYP1A1
      polymorphisms were not associated with the development of UL in the cases
      reported here. 

PMID- 24567939
TI  - The effect of camphor on sex hormones levels in rats.
AB  - In some traditional therapies, it has been claimed that camphor (a crystalline
      ketone obtained from cinnamomum camphora) would be a suppressor of sexual
      behaviors and sex hormones. This study evaluated the effects of camphor on sex
      hormones, like luteinizing hormone (LH), follicle-stimulating hormone (FSH) and
      testosterone. In this experimental study, 56 male rats were divided into 5
      groups, including control (n=12), sham (n=11) and three treatment groups (n=11)
      in three different doses. The sham groups received daily intra peritoneal (IP)
      injections of the vehicle (ethanol 10%) for 30 days. Three treatment groups
      received different daily IP injections of the camphor (1, 2 and 5 mg/Kg) for 30
      days and the control groups didn't received anything. Serums were used for
      assaying LH, FSH and testosterone. The level of LH significantly increased in all
      doses of camphor among the treatment groups as compared to the control (p<0.05),
      but camphor in doses 2 and 5 mg/Kg significantly reduced the FSH level as
      compared to control group (p<0.05). No significant changes were seen in
      testosterone levels. Camphor increased level of LH, decreased level of FSH,
      whereas it failed to change level of testosterone. The claim of inhibitory effect
      of camphor on sexual activity could not be confirmed by this study. More
      investigations in this field are suggested. 

PMID- 24567940
TI  - Study of sperm reproductive parameters in mature zanjani viper.
AB  - OBJECTIVE: Zanjani viper (Vipera albicornuta) is an endemic venomous snake in
      East Azerbai- jan Province, Iran which is medically important due to its
      application for antivenin production in the laboratory. We need to produce this
      snake in captivity. This study was conducted to charac- terize mature male
      Zanjani viper and to evaluate its sperm reproductive parameters. MATERIALS AND
      METHODS: This applied- descriptive study was conducted on twenty Zan- jani viper
      samples collected from Ag Dag Mountain in East Azarbaijan Province, Iran, between
      September and October 2010. After the snakes were anesthetized and sacrificed
      humanly, their morphometric specifications and sperm reproductive parameters,
      including concentration, motility, vitality, morphology, and survival time, were
      measured. RESULTS: MORPHOMETRIC SPECIFICATIONS AND EVALUATION OF SPERMS OF THE
      SNAKE SHOWED THE FOLLOWING INFORMATION: Zanjani male viper, body length of 73.65
      +/- 4.35 cm, tail length of 5.465 +/- 0.48 cm, and mature snakes with testicular
      volumes of 0.61 +/- 0.81 ml (right) and of 0.46 +/- 0.17 ml (left). Our findings
      revealed average sperm concen- tration of 0.47 +/- 0.1 *10(6)ml(-1), motility of
      49 -55 %, vitality of 46.11 +/- 9.63 %, normal morphology of 61.71 +/- 5.3%, and
      survival time of 6 +/- 2 hours at the laboratory tem- perature. Statistical
      analyses were performed using Student's t test for comparison of two values, and
      one-way ANOVA was applied where three values were compared. CONCLUSION: Results
      suggest that mature Zanjani male viper with mature sperms in its vas deferens is
      present in late summer and early autumn seasons in Bostanabad County, Iran.

PMID- 24567942
TI  - Tail flick modification of orexin-a induced changes of electrophysiological
      parameters in the rostral ventromedial medulla.
AB  - OBJECTIVE: It is well known that intracerebroventricular (ICV) and supraspinal
      injections of orexin-A elicit analgesia, but the mechanism(s) of action remains
      unidentified. This study aims to characterize the effect of orexin-A on rostral
      ventromedial medulla (RVM) neurons which are involved in the descending
      nociception modulating pathway. MATERIALS AND METHODS: In this experimental
      study, we injected orexin-A or vehicle di- rectly into rats' ICV while the tail
      flick (TF) latencies were measured and the on- and off-cell firing activities
      were monitored for more than 60 minutes. RESULTS: In response to noxious stimuli
      on the tail, we observed increased firing rate of on-cells and a decreased
      association with the firing rate of off-cells and in neutral cells the firing
      rate was unchanged just prior to tail flicking. ICV injection of orexin-A
      decreased the spontaneous firing rate of on-cells (the type of RVM neurons
      believed to have facilitatory action on nociception). Furthermore, orexin-A
      increased firing rate of off-cells (the type of RVM neurons believed to have an
      inhibitory action on nocicep- tion). Orexin-A reduced the TF-related responses of
      on-cells and TF-related pause duration of off-cells. CONCLUSION: These results
      have shown that the analgesic effect produced by orexin-A may be induced by
      brainstem neurons. It is suggested that the orexinergic system from the
      hypothalamus to the RVM may have a potential role in modulation of nociceptive
      transmission.

PMID- 24567941
TI  - Transplantation of adult monkey neural stem cells into a contusion spinal cord
      injury model in rhesus macaque monkeys.
AB  - OBJECTIVE: Currently, cellular transplantation for spinal cord injuries (SCI) is
      the subject of numerous preclinical studies. Among the many cell types in the
      adult brain, there is a unique subpopulation of neural stem cells (NSC) that can
      self-renew and differentiate into neurons. The study aims, therefore, to explore
      the efficacy of adult monkey NSC (mNSC) in a primate SCI model. MATERIALS AND
      METHODS: In this experimental study, isolated mNSCs were analyzed by flow
      cytometry, immunocytochemistry, and RT-PCR. Next, BrdU-labeled cells were
      transplanted into a SCI model. The SCI animal model was confirmed by magnetic
      resonance imaging (MRI) and histological analysis. Animals were clinically
      observed for 6 months. RESULTS: Analysis confirmed homing of mNSCs into the
      injury site. Transplanted cells expressed neuronal markers (TubIII). Hind limb
      performance improved in trans- planted animals based on Tarlov's scale and our
      established behavioral tests for monkeys. CONCLUSION: Our findings have indicated
      that mNSCs can facilitate recovery in contusion SCI models in rhesus macaque
      monkeys. Additional studies are necessary to determine the im- provement
      mechanisms after cell transplantation.

PMID- 24567943
TI  - Real-Time Assay as A Tool for Detecting lytA Gene in Streptococcus pneumoniae
      Isolates.
AB  - OBJECTIVE: In-time diagnosis of Streptococcus pneumoniae (S. pneumonia) can play
      a significant role in decreasing morbidity and mortality rate. Applying molecular
      methods has gained popularity due to the existing limits of routine diagnostic
      methods. Examining the expression of different genes of this bacterium through
      different molecular methods suggests that lytA gene has a higher sensitivity and
      specificity in diagnosis of Streptococcus pneumoniae. The aim of this study was
      to evalutate lytA gene expression in diagnosis of invasive S. pneumonia in
      culture positive specimens by real-time polymerase chain reaction (PCR).
      MATERIALS AND METHODS: IIn this a descriptive study, All received specimens were
      isolated to identify S. pneumoniae. DNA was then extracted and after optimizing
      the test and determining the detection limit, samples were tested by real-time
      PCR using lytA gene primers. RESULTS: Twenty seven isolates were diagnosed as S.
      pneumoniae. In all, the extracted DNA was positive in real-time method. The
      electrophoresis of the products also confirmed the presence of single product b
      along with the 53 base pair fragment. The detection limit of the test was less 6
      colony forming unit (CFU). CONCLUSION: Real-Time PCR seems to provide reliable
      and rapid results. We suggest that this test should be conducted on the
      preliminary isolated specimens, since applying various biochemical tests need one
      extra working day.

PMID- 24567944
TI  - Histopathological and behavioral assessment of toxin-produced cerebellar lesion:
      a potent model for cell transplantation studies in the cerebellum.
AB  - OBJECTIVE: The cerebellum is a key structure involved in coordinated motor
      planning, cognition, learning and memory functions. This study presents a
      permanent model of a toxin produced cerebellar lesion characterized according to
      contemporary motor and cognitive abnormalities. MATERIALS AND METHODS: In this
      experimental study, slow administration of quinolinic acid (QA, 5 ul of 200 umol,
      1 ul/minute) in the right cerebellar hemisphere (lobule VI) caused noticeable
      motor and cognitive disturbances along with cellular degeneration in all treated
      animals. We assessed behavioral and histopathological studies over ten weeks
      after QA treatment. The data were analyzed with ANOVA and the student's t test.
      RESULTS: The QA treated group showed marked motor learning deficits on the
      rotating rod test (p=0.0001), locomotor asymmetry on the cylinder test
      (p=0.0001), dysmetria on the beam balance test (p=0.0001), abnormalities in
      neuromuscular strength on the hang wire test (p=0.0001), spatial memory deficits
      in the Morris water maze (MWM, p=0.001) and fear conditioned memory on the
      passive avoidance test (p=0.01) over a ten-week period compared with the control
      animals. Histopathological analysis showed loss of Purkinje cells (p=0.001) and
      granular cell density (p=0.0001) in the lesioned hemisphere of the cerebellum.
      CONCLUSION: Results of the present study show that QA can remove numerous cells
      which respond to this toxin in hemispheric lobule VI and thus provide a potential
      model for functional and cell-based studies.

PMID- 24567945
TI  - Improvement in The Function of Isolated Rat Pancreatic Islets through Reduction
      of Oxidative Stress Using Traditional Iranian Medicine.
AB  - OBJECTIVE: Pancreatic islets have fewer antioxidant enzymes than other tissues
      and thus are vulnerable to oxidative stress. In the present study, the effects of
      nine specifically selected Iranian medical plants on the mitochondria function
      and survival of isolated rat islets were examined. MATERIALS AND METHODS: In this
      experimental study, following laparotomy, pancreases of rats were removed and the
      islets isolated and incubated in vitro for 24 hours. Logarithmic doses of plant
      materials were added to the islets and incubated for an additional 24 hours after
      which the viability of the cells and production of reactive oxygen species (ROS)
      were measured. Levels of insulin production in relation to static and stimulated
      glucose concen- trations were also determined. RESULTS: The tested compounds
      markedly increased survival of the islet cells, their mi- tochondrial activity,
      and insulin levels at the same time as reducing production of ROS. Greatest
      effects were observed in the following order: Peganum harmala, Glycyrrhiza
      glabra, Satureja hortensis, Rosmarinus officinalis, Teucrium scordium, Aloe vera,
      Zingiber officinale, Silybum marianum, and Hypericum perforatum at doses of 10,
      10(3), 10(4), 10, 10(2), 10(2), 10(-1), 10 and 10(3)MUgmL(-1), respectively.
      CONCLUSION: Based on these results, we suggest that pretreatment with these
      select- ed Iranian medical plants can improve the outcomes of pancreas
      transplants and grafts through the control of oxidative stress damage.

PMID- 24567946
TI  - Effect of Intra CA1 and Intraperitoneal Administration of Opioid Receptor
      Modulating Agents on The Anxiolytic Properties of Nano and Conventional ZnO in
      Male Rats.
AB  - OBJECTIVE: Nano components are today's new wonder material. However, the safety
      or toxicity of these components in humans is not yet clear. In a previous study
      we indicated that nano ZnO (nZnO) has a stronger anxiolytic effect compared to
      the conventional ZnO (cZnO). The present study was designed to evaluate the
      intraperitoneal administration of an opioidergic receptor agonist and antagonist
      of as well as the intra CA1 administration of an opioidergic receptor antagonist
      on the anxiolytic properties of nano and conventional ZnO in adult male Wistar
      rats. MATERIALS AND METHODS: In this experimental study, rats received drugs via
      two modes of injection; intraperitoneal (IP.) and intra CA1 (intra hippocampus,
      CA1 area). Firstly, nZnO (5, 10, 20 mg/kg), cZnO (5, 10, 20 mg/kg), morphine 6
      mg/kg, and naloxone 1 mg/kg were injected IP and naloxone 1ug/rat was injected
      intra CA1. Subsequently, morphine and na- loxone (IP and intra CA1) were co
      injected with the effective dose of nZnO and cZnO. An elevated plus maze was used
      to evaluate anxiety related behavior and anxiety parameters 30 minutes after the
      second injection. RESULTS: The results indicated that the anxiolytic effects of
      nZnO 5 mg/kg and cZnO 10 mg/kg were equal. When injected intraperitoneally,
      naloxone increased anxiety but did not inhibit the anxiolytic effect of nZnO and
      cZnO. The anxiolytic effects of morphine potentiated the anxio- lytic effects of
      ZnO, particularly nZno. When introduced via intra CA1 injection naloxone alone
      had no effect on anxiety behaviors and did not inhibit the anxiolytic effect of
      nZnO. CONCLUSION: It seems that the opioidergic system activity involved in the
      anxiolytic effect of nano and conventional ZnO may operate through shared and
      unshared pathways.

PMID- 24567947
TI  - The Role of CD14 and CTLA4 Gene Polymorphisms in Risk of Celiac Disease among
      Patients of Iranian Ethnicity.
AB  - OBJECTIVE: Celiac disease (CD) is developed via autoimmune reactions against
      gluten which is mainly found in grains. Although HLA DQB1 locus is the most
      important genetic susceptibility to CD, some other variants such as A49G and
      G1359T of CTLA4 and CD14 genes respectively have been proposed as CD predisposing
      genetic factors in many vari- ous studies. We aimed to assess possible roles of
      A49G and G1359T polymorphisms in CD susceptibility in the Iranian population.
      MATERIALS AND METHODS: In this case-control, one hundred CD patients and 100
      healthy matched controls with average age of 30-33 years were selected. They were
      genotyped for both A49G and G1359T polymorphisms using polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP). RESULTS: There was no
      association between genotypes of A49G variant of CTLA4 and risk of CD (p<0.05).
      The G1359T polymorphism of CD14 gene also did not show any significant
      association with risk of CD among the studied population. However, patients with
      CD14 T/T genotype were more classified in the severe form (Marsh III) of CD,
      showing border line significance (p<0.05). CONCLUSION: No association was
      identified between the combination of 1359T and A49G alleles with risk of CD.
      These lacks of association could be due to small sample size and considering
      further studies in various populations and ethnicities seems to be required.

PMID- 24567948
TI  - Osteoclast-like Cells in Early Zebrafish Embryos.
AB  - OBJECTIVE: Genes involved in bone and tissue remodelling in the vertebrates
      include matrix metalloproteinase-9 (mmp-9), receptor activator of necrosis factor
      kappa-beta (rank), cathepsin-k (Ctsk) and tartrate-resistant acid phosphatase
      (TRAcP). We examine whether these markers are expressed in cells of zebrafish
      embryos of 1-5 days post fertilization. We also examine adult scales, which are
      known to contain mature osteoclasts, for comparison. MATERIALS AND METHODS: In
      this experimental study, in situ hybrdisation, histochemistry and serial plastic
      and paraffin sectioning were used to analyse marker expression. RESULTS: We found
      that mmp-9 mRNA, TRAcP enzyme and Ctsk YFP protein were expressed in
      haematopoietic tissues and in the cells scattered sparsely in the embryo. Ctsk
      and rank mRNA were both expressed in the branchial skeleton and in the developing
      pectoral fin. In these skeletal structures, histology showed that the expressing
      cells were located around the developing cartilage elements, in the parachondral
      tissue. In a transgenic zebrafish line with YFP coupled to Ctsk promoter, Ctsk
      expressing cells were found around pharyngeal skeletal elements. To see whether
      we could activate osteoclasts, we exposed prim-6 zebrafish embryos to a mixture
      of 1 uM dexamethasone and 1 uM vitaminutes D3. These compounds, which are known
      to trigger osteoclastogenensis in cell cultures, lead to an increase in intensity
      of Ctsk YFP expression around the skeletal elements. CONCLUSION: Our findings
      show that cells expressing a range of osteoclast markers are present in early
      larvae and can be activated by the addition of osteoclastogenic compounds.

PMID- 24567950
TI  - New insights into carbon dioxide interactions with benzimidazole-linked polymers.
AB  - A synergistic experimental and theoretical study (DFT) highlights the impact of
      material design at the molecular and electronic levels on the binding affinity
      and interaction sites of CO2 with benzimidazole-linked polymers (BILPs); CO2 is
      stabilized by benzimidazole units through Lewis acid-base (N...CO2) and aryl C
      H...O=C=O interactions.

PMID- 24567951
TI  - An unusual macrocyclization reagent for highly selective one-pot synthesis of
      strained macrocyclic aromatic hexamers.
AB  - One-pot, multi-molecular macrocyclization allows the highly selective preparation
      of strained macrocyclic aromatic hexamers structurally stabilized by an inward
      pointing continuous hydrogen-bonding network. 

PMID- 24567949
TI  - Chip based single cell analysis for nanotoxicity assessment.
AB  - Nanomaterials, because of their tunable properties and performances, have been
      utilized extensively in everyday life related consumable products and technology.
      On exposure, beyond the physiological range, nanomaterials cause health risks via
      affecting the function of organisms, genomic systems, and even the central
      nervous system. Thus, new analytical approaches for nanotoxicity assessment to
      verify the feasibility of nanomaterials for future use are in demand. The
      conventional analytical techniques, such as spectrophotometric assay-based
      techniques, usually require a lengthy and time-consuming process and often
      produce false positives, and often cannot be implemented at a single cell level
      measurement for studying cell behavior without interference from its surrounding
      environment. Hence, there is a demand for a precise, accurate, sensitive
      assessment for toxicity using single cells. Recently, due to the advantages of
      automation of fluids and minimization of human errors, the integration of a cell
      on-a-chip (CoC) with a microfluidic system is in practice for nanotoxicity
      assessments. This review explains nanotoxicity and its assessment approaches with
      advantages/limitations and new approaches to overcome the confines of traditional
      techniques. Recent advances in nanotoxicity assessment using a CoC integrated
      with a microfluidic system are also discussed in this review, which may be of use
      for nanotoxicity assessment and diagnostics. 

PMID- 24567952
TI  - Profiling of RNA modifications by multiplexed stable isotope labelling.
AB  - The combination of (15)N/(13)C stable isotope labelling (SIL) and LC-MS/MS
      revealed a total of 52 modifications in RNA from E. coli and yeast, including 10
      previously undescribed modifications. Two modifications, N-ribosylnicotinamide
      and 2-methylthioadenosine, were newly detected in species hitherto thought not to
      contain these modifications. 

PMID- 24567953
TI  - Turn-on fluorescent probes for nitric oxide sensing based on the ortho
      hydroxyamino structure showing no interference with dehydroascorbic acid.
AB  - A new family of fluorescent synthetic molecular probes for nitric oxide sensing
      based on ortho-hydroxyamino-triarylpyrylium salts is presented. 

PMID- 24567954
TI  - Molecular inversion probe-based SPR biosensing for specific, label-free and real
      time detection of regional DNA methylation.
AB  - DNA methylation has the potential to be a clinically important biomarker in
      cancer. This communication reports a real-time and label-free biosensing strategy
      for DNA methylation detection in the cancer cell line. This has been achieved by
      using surface plasmon resonance biosensing combined with the highly specific
      molecular inversion probe based amplification method, which requires only 50 ng
      of bisulfite treated genomic DNA. 

PMID- 24567956
TI  - Guest editors' introduction to the special section on bioinformatics research and
      applications.

PMID- 24567957
TI  - Environmental scan of interprofessional collaborative practice initiatives.
AB  - Interprofessional collaboration in health care is high on the policy agenda in
      Canada. There is evidence that governments, academic institutions, regulatory
      bodies and health services are developing directions, policies and strategies
      with collaboration in mind. The Ottawa Hospital (TOH) received governmental
      funding to implement The Ottawa Hospital Inter-Professional Model of Patient
      Care.Prior to implementing our model, we conducted an environmental scan to
      identify initiatives related to interprofessional collaboration in clinical
      settings. A historical method was used to understand the chronological
      development of interprofessional collaboration within the health field over the
      last 10 years. Critical browsing was used to search, select and summarize
      information found on the web. Fifty two documents were critically reviewed; 27
      documents were retained for further analysis and inclusion.The information was
      analyzed according to three main parameters: source, summary and relevance to our
      project. The five broad themes identified are: promotion, networking, evidence,
      resources and linkage between interprofessional education and care. This seems an
      accurate reflection of the current state of this area; there is active promotion
      and networking, concrete frameworks and funds but few published results regarding
      the efficacy of implementing IPC in health care organizations. As experience with
      the approach accumulates, evidence should grow

PMID- 24567958
TI  - The university/community partnership: transdisciplinary course development.
AB  - This paper describes the process of expanding the knowledge base and clinical
      practice for students in professional preparation programs in social work,
      nursing and education. Through a partnership of university faculty and
      administrators of a private school for students with learning and behavior
      problems, a transdisciplinary course was designed to address the need for
      providing future professionals an opportunity to understand multiple perspectives
      in the design of clinical interventions.The process of defining the course
      content, identifying appropriate required reading, and building connections to
      field work was a collaborative effort and less problematic than the logistics of
      implementation. Negotiating the administrative barriers to interprofessional
      collaboration involving curriculum innovation was more challenging. Discussion
      also includes the need for a shared vision and responsibility for improving
      practice, the practical implications of university funding and the benefits and
      challenges of transforming current treatment paradigms into one focused on
      interprofessional care.

PMID- 24567955
TI  - Autocrine/paracrine modulation of baroreceptor activity after  antidromic
      stimulation  of aortic depressor nerve in vivo.
AB  - Activation of the sensory nerve endings of non-myelinated C-fiber afferents
      evokes release of autocrine/paracrine factors that cause localized vasodilation,
      neurogenic inflammation, and modulation of sensory nerve activity. The aims of
      this study were to determine the effect of antidromic electrical stimulation on
      afferent baroreceptor activity in vivo, and investigate the role of endogenous
      prostanoids and hydrogen peroxide (H2O2) in mediating changes in nerve activity.
      Baroreceptor activity was recorded from the left aortic depressor nerve (ADN) in
      anesthetized rats before and after stimulating the ADN for brief (5-20 s)
      periods. The rostral end of the ADN was crushed or sectioned beforehand to
      prevent reflex changes in blood pressure. Antidromic stimulation of ADN using
      parameters that activate both myelinated A-fibers and non-myelinated C-fibers
      caused pronounced and long-lasting (> 1 min) inhibition of baroreceptor activity
      (n = 9, P < 0.05), with the magnitude and duration of inhibition dependent on the
      duration of the stimulation period (n = 5). Baroreceptor activity was only
      transiently inhibited after selective stimulation of A-fibers. The inhibition of
      activity after antidromic stimulation of A and C fibers was prolonged after
      administration of the cyclooxygenase inhibitor indomethacin (5 mg/kg, IV, n = 7)
      and abolished after administration of PEG-catalase (104 units/kg, IV, n = 7), an
      enzyme that catalyzes the decomposition of H2O2 to water and oxygen. The results
      demonstrate a long-lasting inhibition of baroreceptor activity after antidromic
      stimulation of ADN and suggest that endogenous prostanoids and H2O2 oppose and
      mediate the inhibition, respectively. These mechanisms may contribute to rapid
      baroreceptor resetting during acute hypertension and be engaged during chronic
      baroreceptor activation therapy in patients with hypertension.

PMID- 24567959
TI  - Retraction notice to "Lower CSF interleukin-6 predicts future depression in a
      population-based sample of older women followed for 17 years" [Brain Behav.
      Immun. 32 (2013) 153-158].

PMID- 24567960
TI  - The development, outline and evaluation of the second level of an
      interprofessional learning programme - listening to the students.
AB  - The delivery and content of interprofessional education (IPE) varies greatly.
      Currently there is little evidence to suggest the most effective approach. This
      paper describes an interprofessional learning programme offered to second year
      healthcare students (IPL2), which was developed together with the students. At
      the outset of developing IPL2, an interprofessional student planning group
      (supported by a facilitator) was formed. The student planning group (SPG)
      reported back their ideas to an IPL steering group. Student feedback forms from
      2005-2006 were used for the review and further development of IPL2. Analysis of
      student feedback was completed using median (for the quantitative elements of the
      form) and content analysis (for the qualitative elements). Post-programme student
      feedback included suggestions such as improvements to the case scenario, issues
      such as the logistical problems associated with students being on placement and
      how to overcome this by expanding the use of a virtual learning environment.
      Student views have informed both the original and ongoing development of IPL2 and
      ensure that the IPL programme remains relevant to the students. This model of
      involving students in the development of IPL has proven effective and can be
      applied to other settings.

PMID- 24567961
TI  - If I had a rich picture. . .: Insights into the use of ''soft'' methodological
      tools to support the development of interprofessional education.
AB  - This paper describes a methodological experiment that aimed to test a small
      number of tools borrowed from Soft Systems Methodology. Those tools were intended
      to support action research for a project in interprofessional educational
      development. The intention with using those tools was two-fold: first, they were
      expected to help structure the analysis of the problem situation that the project
      was to address; second, they were to facilitate and document the project
      management process itself, by allowing for the different voices within the
      interprofessional project team to be heard. The paper relates how the tools
      functioned relatively successfully as analytical devices for the action
      researcher, but did not significantly contribute to further interprofessional
      collaboration or enhance dialogue between the action researcher and the project
      members. Issues of how to use the tools to support more effectively the existing
      dialogue across professional cultures and traditions are discussed.

PMID- 24567962
TI  - Bridging the gap: enhancing interprofessional education using simulation.
AB  - Simulated learning and interprofessional education (IPE) are increasingly
      becoming more prevalent in health care curriculum. As the focus shifts to patient
      centred care, health professionals will need to learn with, from and about one
      another in real-life settings in order to facilitate teamwork and collaboration.
      The provision of simulated learning in an interprofessional environment helps
      replicate these settings thereby providing the traditional medical education
      model with opportunities for growth and innovation. Learning in context is an
      essential psychological and cognitive aspect of education.This paper offers a
      conceptual analysis of the salient issues related to IPE and medical simulation.
      In addition, the paper argues for the integration of simulation into IPE in order
      to develop innovative approaches for the delivery of education and improved
      clinical practice that may benefit students and all members of the health care
      team.

PMID- 24567963
TI  - Evaluation of interprofessional training in home care.
AB  - The increasing number of patients in home care and the importance of teamwork
      make it important to provide successful ways of interprofessional learning for
      students. The aim of this study was to evaluate a group of undergraduate
      students' experiences of a one-day interprofessional home care training in a
      realistic setting. A study group comprised of 88 students and a control group
      with 182 students answered the questionnaire. In the study group the students
      practised interprofessional learning for a fictitious case in a real flat. The
      clinical education was performed in five steps. A group of local instructors
      supported the students during the day. The result showed that compared to the
      students in the control group the students in the study group had received a
      higher level of understanding or satisfaction in all comparable questions. The
      training day seemed to be especially important for the physiotherapy students.
      The students also gave feedback which can be used for future improvements.The
      arranged one-day home care training seemed to be a successful platform for
      interprofessional learning in primary health care. Nonetheless, certain logistics
      problems and the participation of medical students are two areas where
      improvement is necessary.

PMID- 24567964
TI  - Learning about each other: students' conceptions before and after
      interprofessional education on a training ward.
AB  - In interprofessional work the striving of the members of each profession to
      establish their own positive in-group identity can be a source of conflict and
      have a negative effect on care. To counteract this,interprofessional training
      wards (IPTWs) have been developed in Sweden. The aim of the present study was to
      investigate similarities and differences in how student nurses, student
      occupational therapists and student social workers perceived their own and the
      other two professions before and after clinical education on an IPTW. Sixteen
      students were interviewed before and after the training on an IPTW in municipal
      care for older people in Sweden. A coding scheme developed in an earlier study
      was used in the analysis of the interviews. The findings indicate that there are
      changes in the students' stereotyped views, enhancing understanding of each
      other's professions after three weeks' clinical education on the IPTW. In some
      areas, however, there are still discrepancies between the description of own
      profession and the others' understanding of this profession that need to be
      confronted. In interprofessional training during education in social and health
      care there needs to be a balance between on the one hand the particular
      professional identity, on the other the shared identity implied by membership of
      the health-care team focusing on a common goal.

PMID- 24567965
TI  - Haptoglobin and myeloperoxidase (- G463A) gene polymorphisms in Brazilian sickle
      cell patients with and without secondary iron overload.
AB  - We aimed to investigate the influence of haptoglobin (Hp) and myeloperoxidase
      (MPO - G463A; dbSNP rs2333227) gene polymorphisms on 78 sickle cell patients of a
      public hospital in the Federal District/Brazil with and without iron overload, to
      evaluate a possible association between these polymorphisms and clinical
      variability, response to treatment and prognosis. Data were obtained through
      laboratory tests, questionnaires, research in medical records and analyses of
      polymorphisms using PCR-based methods. Positive correlations were found between
      Hp and ferritin levels, hydroxyurea treatment, hospitalisation for and sequelae
      from stroke; and between MPO and number of hospitalizations in the past 12 months
      and splenectomy. Significant associations of specific Hp genotypes with
      comorbidities were also found, while results suggested that MPO AA homozygosis
      could increase effects of asplenia. Deviation from Hardy-Weinberg equilibrium,
      compatible with heterozygous deficit, was observed for Hp polymorphism. Odds
      ratio suggested the possibility that increased chance of hospitalisation for
      stroke (OR = 6.346; IC 95% = 1.56-25.79; p = 0.005) and sequelae of stroke (OR =
      6.556; IC 95% = 1.578-27.237; p = 0.005) could be associated with lower frequency
      of 1S-2 than expected. In the interaction analyses, significant effects between
      subjects were shown only in the group without overload for Hp polymorphism in hs
      CRP levels (p = 0.000) and number of transfusions (p = 0.018), and for MPO
      polymorphism (p = 0.000) and the interaction Hp/MPO (p = 0.000) in hs-CRP values.
      Results corroborate others indicating biological differences between Hp*1 alleles
      and highlight the importance of this study in understanding the biological
      significance of Hp and MPO polymorphisms in clinical variability and response to
      treatment of sickle cell patients.

PMID- 24567966
TI  - Integrating services for disabled children and their families in two English
      local authorities.
AB  - Recent critiques challenge the assumption that working in a more integrated way
      will necessarily improve the quality of services received by children in need and
      their families. This paper explores the process of service integration for
      disabled children and their families in two inner city local authorities in
      England, with particular reference to ways in which history and geography impact.
      Service users and their carers hold similar ideas about features important in
      order for integration to be successful -including clear signposts into and
      through services and reliable and respectful relationships with professionals in
      the context of inclusive service planning. Professionals concur. They appear to
      benefit from the establishment of clear processes and boundaries between
      services, enabling them to build bridges between organizations towards the
      creation of innovative, integrated services.

PMID- 24567967
TI  - Improving interprofessional teamwork in obstetrics: a Crew Resource Management
      based training programme.

PMID- 24567968
TI  - Health and disability: interprofessional education of healthcare students.

PMID- 24567969
TI  - Controversy surrounds England's new NHS database.

PMID- 24567970
TI  - Interprofessional care in the management of a chronic childhood condition:
      Developmental Coordination Disorder.

PMID- 24567971
TI  - New guideline on beta blockers challenges ESC advice.

PMID- 24567972
TI  - Indonesia to revive national family planning programme.

PMID- 24567973
TI  - Funding: NINDS seeks to reshape brain research.

PMID- 24567974
TI  - Govert Bidloo's liver: human symmetry reflected.

PMID- 24567975
TI  - Decision on payment for initial emergency treatment.

PMID- 24567976
TI  - Reply: To PMID 23493896.

PMID- 24567978
TI  - Notice of retraction.

PMID- 24567977
TI  - The effects of continuous positive airways pressure therapy on cardiovascular end
      points in patients with sleep-disordered breathing and heart failure: a meta
      analysis of randomized controlled trials.
AB  - In patients with sleep-disordered breathing and heart failure, continuous
      positive airway pressure has been found to be associated with an improvement in
      cardiovascular end points. We conducted a systematic review of the current
      literature and a meta-analysis to pool data from 15 published randomized
      controlled trials. End points analyzed were left ventricular ejection fraction,
      diastolic blood pressure, systolic blood pressure, heart rate, and mortality. A
      fixed effects model was used for end points demonstrating homogeneity among
      included studies, whereas a random effects model was used for end points
      demonstrating heterogeneity among included studies. A significant improvement in
      left ventricular ejection fraction was noted with continuous positive airway
      pressure (mean difference, 5.05%; 95% confidence interval [CI]: 3.72 to 6.38),
      diastolic blood pressure (mean difference, -1.67; 95% CI: -3.09 to -0.25), and
      heart rate (mean difference, -5.92; 95% CI: -10.12 to-1.72). No significant
      changes in mortality (odds ratio, 0.63; 95% CI: 0.40 to 1.00) and systolic blood
      pressure were noted (mean difference, -6.35; 95% CI: -16.11 to 2.41). The
      analysis also revealed the need for additional studies to clarify the
      associations noted and the presence of publication bias with small studies with a
      paucity of small studies with negative results. In this meta-analysis, treatment
      with continuous positive airways pressure was associated with improvements in
      ejection fraction, diastolic blood pressure, and heart rate in patients with
      sleep-disordered breathing and congestive heart failure.

PMID- 24567979
TI  - Assessing the role of attachment to God, meaning, and religious coping as
      mediators in the grief experience.
AB  - Research has examined the relationship of styles of attachment to others and
      meaning with grief and the stress-related growth process. Less has been written
      on styles of attachment to God and patterns of religious coping and how these
      constructs may impact adjustment in persons dealing with loss. This study
      examines the roles of attachment to God, meaning, and religious coping as
      mediators in the grief experience for a sample of 93 individuals who experienced
      a significant death in the prior year. Results suggest that a more secure style
      of attachment to God was directly and indirectly associated with lower depression
      and grief and increased stress-related growth for this sample. Meaning, defined
      as a sense of purpose and coherence, also emerged as an important construct in
      this process. Overall goodness-of fit statistics were examined for competing
      models using structural equation modeling. Secure attachment to God, meaning, and
      positive religious coping were found to have significant direct and indirect
      effects on grief and stress-related growth. For some individuals, attachment to
      God may be an important construct in the experience of meaning following a
      significant death and may have tremendous potential in its direct and indirect
      effects on overall outcomes.

PMID- 24567980
TI  - Validation of a new measure of the concept of good death among Taiwanese
      children.
AB  - The purpose of this study was to develop and validate an instrument to measure
      dimensions of the concept of a good death held by Taiwanese children. The sample
      consisted of 1,698 Taiwanese children, approximately 12-14 years of age.
      Participants completed the self-administered Good Death Concept Scale (GDCS),
      which consists of 30 statements describing potentially important contributors to
      a good death that had been identified in the relevant literature. Findings
      indicated that the GDCS is reliable and valid, as evidenced by the acceptable
      reliability, the consistent item-total correlations, the successful confirmatory
      factor analysis modeling, and the significant associations between the scale
      measuring concepts of a good death and 2 standardized scales (the
      Multidimensional Fear of Death Scale and the Death Attitude Profile-Revised). The
      results of this study suggest that GDCS measures 8 distinct domains, each
      reflecting a different aspect of good death: physical/biological, psychological,
      social, cognitive, altruistic, spiritual, affective, and rational.

PMID- 24567981
TI  - A life history of a Korean adolescent girl who attempted suicide.
AB  - The present study explores the life history of a South Korean adolescent girl who
      attempted suicide. The study focuses on how sociocultural values affected her
      suicide attempt and how she made meaning out of the experience. The results
      revealed that her life history was a process of seeking independence and
      autonomy, and freeing herself from social stigmatization. The study highlights
      the need for professionals to examine the sociocultural context of adolescents,
      along with a consideration of their developmental characteristics and family
      relationships in order to understand adolescent suicidal behaviors.

PMID- 24567982
TI  - Religiosity and the construction of death in Turkish death announcements, 1970
      2009.
AB  - Death and rituals performed after death reflect and reproduce social distinctions
      despite death's popular reputation as a great leveler. This study examines
      expressions of religiosity and constructions of death in Turkish death
      announcements, paying particular attention to gendered, ethnic, and temporal
      variations as well as markers of status and cultural distinction. Death
      announcements in Turkey occupy a liminal position between obituaries and death
      notices: Unlike obituaries, no editorial decisions are involved in their
      publications. However, unlike death notices, Turkish announcements are venues for
      expressions of culturally scripted individual decisions. These large and
      decentralized collections of private decisions display rigid genre
      characteristics involving formulaic phrases but also change over time to reflect
      social, cultural, and economic changes in Turkish society. The present study
      focuses on a sample (N = 2,812) of death announcements in a major Turkish daily
      newspaper (Hurriyet) from 1970 to 2009. Results show that death announcements in
      Turkey increasingly rely on an emotional tone of loss and bereavement that
      replace constructions of death in a more detached and distant language and that
      religious and secular preferences in the language of announcements are an
      important domain in which cultural battles are fought and the participation
      patterns of new middle classes are negotiated.

PMID- 24567983
TI  - Associations between prolonged grief disorder, depression, posttraumatic stress
      disorder, and anxiety in Rwandan genocide survivors.
AB  - A number of studies have demonstrated that symptoms of prolonged grief disorder
      (PGD) represent a symptom cluster distinct from bereavement-related depression,
      anxiety, and posttraumatic stress disorder (PTSD). The aim of the present study
      was to confirm and extend these findings using the most recent criteria defining
      PGD. The authors interviewed a total of 400 orphaned or widowed survivors of the
      Rwandan genocide. The syndromes were strongly linked to each other with a high
      comorbidity. Principal axis factoring resulted in the emergence of 4 different
      factors. The symptoms of depression, along with the cognitive, emotional, and
      behavioral symptoms of PGD, loaded on the first factor, symptoms of anxiety on
      the second factor, symptoms of PTSD on the third factor, and the separation
      distress symptoms of PGD on the fourth factor. This indicates that the concept of
      PGD includes symptoms that are conceptually related to depression. However, the
      symptom cluster of separation distress presents a grief-specific dimension that
      may surface unrelated to depressive symptoms.

PMID- 24567984
TI  - A phenomenological study of family needs following the suicide of a teenager.
AB  - The objective of this phenomenological study was to develop an understanding of
      family needs following the suicide of a teenager. Six parent units living in the
      Midwest who lost a teenager to suicide were interviewed. Participants indicated
      several key themes that describe a parent's needs following the suicide of a
      teenager. These needs were organized into 6 main categories: (a) support by
      listening and responding, (b) support from another suicide survivor, (c) support
      in finding direction, (d) support when viewing the deceased teen, (e) support in
      remembering the teen, and (f) support in parents giving back to the community.

PMID- 24567985
TI  - Cultural implications of death and loss from AIDS among women in South Africa.
AB  - Over 1.8 million people have died of AIDS in South Africa, and it continues to be
      a death sentence for many women. The purpose of this study was to examine the
      broader context of death and loss from HIV/AIDS and to identify the cultural
      factors that influenced existing beliefs and attitudes. The participants included
      110 women recruited from 3 communities in South Africa. Focus group methodology
      was used to explore their perceptions surrounding death and loss from HIV/AIDS.
      Using the PEN-3 cultural model, our findings revealed that there were positive
      perceptions related to how women cope and respond to death and loss from
      HIV/AIDS. Findings also revealed existential responses and negative perceptions
      that strongly influence how women make sense of increasing death and loss from
      HIV/AIDS. In the advent of rising death and loss from HIV/AIDS, particularly
      among women, interventions aimed at reducing negative perceptions while
      increasing positive and existential perceptions are needed. These interventions
      should be tailored to reflect the cultural factors associated with HIV/AIDS.

PMID- 24567986
TI  - A traumatic death support group program: applying an integrated conceptual
      framework.
AB  - This article describes an 8-week, curriculum-based traumatic death support group
      program that is offered at Bo's Place, a grief and bereavement center in Houston,
      Texas. The program was implemented in 2006 in an effort to help family members
      who had experienced a death in the family by suicide, murder, accident, or sudden
      medical problem. The program provides the opportunity for families to come to the
      center and engage in selected activities as a unit, while also providing adults
      and children the opportunity to participate in separate support groups with
      curricula adapted to different age levels. The program uses an integrated
      conceptual framework that draws upon elements from a variety of theoretical and
      conceptual models related to grief. The purpose of the program is to provide
      multiple paths for progress in the grief journey for the bereaved. In 2008, Bo's
      Place incorporated a brief questionnaire into the weekly meetings, in an effort
      to gain a better understanding of the perceptions of adult participants of the
      program and their own progress in their grief. The questionnaire asked adults to
      provide self-ratings of their perceptions of support from the program and of
      their progress in their grief journey. The positive results from this pilot study
      have encouraged Bo's Place to develop plans for more rigorous research into the
      mechanisms that contribute to progress in the grief journey for bereaved adults
      and children.

PMID- 24567987
TI  - Do people whose names begin with "D" really die young?
AB  - It has been reported that professional baseball players whose first names begin
      with the letter "D" tend to die relatively young (E. L. Abel & M. L. Kruger,
      2010). However, the statistical evidence for this claim is based on selective
      data and a statistical test that ignores important confounding influences. A
      valid test applied to more comprehensive data from the same source does not show
      a statistically significant relationship between initials and longevity. In
      addition, data for the years 1960 through 2004 for 6.7 million White, non
      Hispanic California decedents do not replicate the claim that D's die young.

PMID- 24567989
TI  - Psychometric properties of a suicide screen for adjudicated youth in residential
      care.
AB  - There is a need to efficiently and effectively screen adjudicated youth residing
      within the juvenile justice system for suicide proneness. Accordingly, in the
      current study, the psychometric properties of the Life Attitude Schedule: Short
      Form (LAS:S), a 24-item risk assessment for suicide proneness, were assessed
      using data from adjudicated youth residing in an alternative sentencing facility
      (n = 130). As predicted, statistically significant correlations were obtained
      between total LAS:S suicide proneness scores and reports of recent suicide
      ideation and hopelessness. Contrary to expectation, the previously reported 2
      factor model for the LAS:S, with Factor 1 representing physical unhealthiness and
      Factor 2 representing psychological death, poorly fit the data. In adjudicated
      youth, we found that a single factor model derived from the 4 LAS:S subscales
      produced a better fit to the data than the 2-factor model. The death-related,
      self-related, injury-related, and negative health-related behaviors contained on
      the LAS:S shared common variance in these youth. A clinical implication is that
      practitioners can effectively use the total LAS:S score when screening
      adjudicated youth for suicide proneness.

PMID- 24567988
TI  - An assessment of social diffusion in the Respecting Choices advance care planning
      program.
AB  - This study examines the potential social diffusion effects of the Respecting
      Choices advance care planning program administered in La Crosse, Wisconsin, since
      1991. The program produces educational materials for patients, trains
      facilitators to help patients prepare for end of life, and ensures that advance
      directives are connected to patients' medical records. Using data from a survey
      of more than 5,000 White Wisconsin high school graduates in their mid-60s, we
      found that participants who were living in the La Crosse area were significantly
      less likely than their peers living elsewhere to have executed a living will or
      appointed a health care power of attorney. This pattern may reflect psychological
      reactance, where individuals reject a message or lesson when they perceive
      compliance as a threat to their autonomy. There was no evidence of social
      diffusion effects; participants who lived in the La Crosse region themselves or
      who had social network members residing in the area were no more likely than
      those with no known ties to the region to have engaged in advance care planning.
      Future studies should explore the processes through which individuals learn and
      share with others their knowledge of advance care planning.

PMID- 24567990
TI  - Death and television: terror management theory and themes of law and justice on
      television.
AB  - Based on terror management theory, it was hypothesized that media choices may be
      affected by the salience of death-related thoughts. Three experiments with
      samples of undergraduate students were conducted to investigate whether such a
      process would affect preferences for law and justice television programming. In
      the first experiment (n = 132), individuals for whom mortality had been made
      salient through experimental induction preferred more programs with law and
      justice themes than individuals for whom mortality had not been made salient. In
      the second experiment (n = 761), this effect was observed regardless of trust in
      law enforcement and only for participants induced to think about death, not those
      induced to think about pain. In the third experiment (n = 163), participants for
      whom mortality was salient who watched a crime drama that showed justice being
      carried out showed a diminished self-enhancing bias compared to participants who
      watched a version of the same program in which justice was thwarted. Results
      indicate that entertainment choices are influenced by thought of death beyond
      simply seeking distraction and that entertainment programming emphasizing justice
      can effectively ameliorate existential anxiety that arises from thoughts of
      death.

PMID- 24567991
TI  - Goals set in the land of the living/dying: a longitudinal study of patients
      living with advanced cancer.
AB  - A longitudinal qualitative research study was undertaken to provide an
      understanding of a prolonged experience of advanced cancer, as seen through the
      eyes of dying individuals. Using a variant of the grounded theory method, the
      authors theoretically sampled, from outpatient clinics in a large comprehensive
      cancer treatment center, 27 patients with either advanced lung or
      gastrointestinal cancer who had an expected survival of up to 2 years. The
      authors conducted a total of 54 interviews with these patients to learn of their
      experience of advanced cancer. The authors represent their experience with the
      core category: striving to grow in the land of the living/dying, symbolizing
      their sense of finding themselves in a borderland between life and death where
      their efforts focused on 3 common goals. controlling dying, valuing life in the
      present, and creating a living legacy. They provide a longitudinal account of how
      these goals were addressed throughout the illness trajectory and discuss the
      theoretical and clinical implications of this understanding for the experience of
      dying from advanced cancer.

PMID- 24567992
TI  - Bereavement experiences of mothers and fathers over time after the death of a
      child due to cancer.
AB  - The authors investigated longitudinally bereavement in mothers and fathers whose
      children died of cancer. Thirty-one parents were interviewed 6 and 18 months post
      death. Analyses revealed parental differences and changes over time: (a)
      employment--fathers were more work-focused; (b) grief reactions--mothers
      expressed more intense grief reactions that lessened over time; (c) coping-
      mothers were more child-focused, fathers more task-focused; (d) relationship with
      bereaved siblings-mothers actively nurtured relationship with child; (e) spousal
      relationship--parents reported diversity in their relationship over time; and (f)
      relationship with extended family--mothers maintained contact with extended
      family more. Findings illustrate parental differences in bereavement over time
      that might be partly socially determined. These findings emphasize the need for
      tailoring bereavement support services in the family.

PMID- 24567993
TI  - Death competence: an ethical imperative.
AB  - The authors argued that death competence, defined as specialized skill in
      tolerating and managing clients' problems related to dying, death, and
      bereavement, is a necessary prerequisite for ethical practice in grief
      counseling. A selected review of the literature tracing the underpinnings of this
      concept reveals how a robust construct of death competence evolved. Using the
      vehicle of a case study, the authors analyzed an example of empathic failure
      resulting from an apparent lack of death competence on the part of a mental
      health provider to illustrate the importance of this characteristic in delivering
      clinically effective and ethically sensitive grief counseling.

PMID- 24567994
TI  - The role of peer relationships in parental bereavement during childhood and
      adolescence.
AB  - This article reviews current knowledge concerning the relationship between peer
      support and adjustment outcomes and experiences for parentally bereaved children.
      A brief overview of the effects of parental bereavement and factors influencing
      immediate and long-term adjustment is provided, followed by an overview of peer
      provided social support and its relationship to adjustment. Current findings on
      the predictive value of peer support for adjustment are then discussed, with
      emphasis on the reciprocal positive and negative influences that peer support and
      adjustment (or lack thereof) exert. Areas of weakness and neglect within this
      domain are noted, with a focus on methodological issues, peer-relevant
      consequences of bereavement in need of further research, and the need for study
      of particular vulnerable subgroups.

PMID- 24567995
TI  - ATTEND: toward a mindfulness-based bereavement care model.
AB  - Few, if any, mindfulness-based bereavement care models exist. The ATTEND
      (attunement, trust, touch, egalitarianism, nuance, and death education) model is
      an interdisciplinary paradigm for providers, including physicians, social
      workers, therapists, nursing staff and others. Using a case example to enhance
      the breadth and depth of understanding, this article focuses on attunement as a
      means to moderate the negative effects of traumatic bereavement, support the
      framework for posttraumatic growth in the bereaved, improve psychological
      outcomes for providers, and set the stage for the other aspects of the ATTEND
      model.

PMID- 24567996
TI  - Do grief self-help books convey contemporary perspectives on grieving?
AB  - Grief therapy and psychology literatures of the modern Western world
      conceptualized bereavement and grief as processes to be "worked through" so that
      other relationships could be pursued. In the last decade or so, however, grief
      theorists have endorsed the value of attaining new meaning(s) and continuing
      bonds with our lost loved ones instead of "moving on from," "letting go of" or
      "achieving closure from" them. This article tracks the evolution of thought
      pertaining to this shift and examines its relevance to grief self-help books that
      may offer Americans guidance in the ways of grieving.

PMID- 24567997
TI  - "I'm not trying to be cured, so there's not much he can do for me": hospice
      patients' constructions of hospice's holistic care approach in a biomedical
      culture.
AB  - The hospice philosophy was founded on a mission to provide comprehensive and
      holistic services to individuals at the end of life. Hospice interdisciplinary
      teams work together to offer therapies such as spiritual services, comfort care,
      and massage therapy to meet patients' physical, psychological, emotional, and
      spiritual needs. Although the hospice philosophy is guided toward patient
      centered care, limited research has examined how patients understand holistic
      care services. Through a social constructionist lens and qualitative interviews,
      we examined hospice patients' understandings of holistic care and argue that
      these perceptions of care are constructed through the biomedical model of
      medicine.

PMID- 24567998
TI  - A nationwide random sampling survey of potential complicated grief in Japan.
AB  - To investigate the prevalence of significant loss, potential complicated grief
      (CG), and its contributing factors, we conducted a nationwide random sampling
      survey of Japanese adults aged 18 or older (N = 1,343) using a self-rating
      Japanese-language version of the Complicated Grief Brief Screen. Among them,
      37.0% experienced their most significant loss by expected non-violent death,
      17.9% by unexpected non-violent death, and 5.5% by violent death. The mean length
      of time since the loss was 11.9 years (SD = 11.6). The percentage of individuals
      with potential CG (5 or higher score on the scale) was 2.5% among those who
      experienced significant loss. The individuals with potential CG showed lower
      mental health scores than those without. Through regression analysis, we found
      the significant effects of gender difference, time since the loss, and the
      interaction of the mode of death, gender of the bereaved, and the kinship
      relationship to the deceased on the CG score. Women who had lost a child by
      sudden or violent death showed significantly higher CG scores, but men did not.
      By comparison, those (particularly men) who had lost a partner by expected or
      sudden nonviolent death showed significantly higher CG scores. The implications
      of the findings are discussed.

PMID- 24567999
TI  - Visiting the site of death: experiences of the bereaved after the 2004 Southeast
      Asian Tsunami.
AB  - The authors examined how many bereaved relatives of Norwegian tourists who
      perished in the 2004 Southeast Asian Tsunami had visited the site of death and
      the most important outcome from the visit. We conducted in-depth interviews (n =
      110) and used self-report questionnaires (Impact of Event Scale-Revised,
      Inventory of Complicated Grief and General Health Questionnaire) in a total of
      130 first-degree family members 2 years post-disaster. Results showed that the
      majority of participants (n = 113; 87%) had visited the site of death. The most
      important outcome was gaining an increased understanding of what occurred (61%)
      and a feeling of closeness to the deceased (27%). Those who had visited the site
      of death reported lower avoidance behavior and higher degree of acceptance of the
      loss than non-visitors. Although this could be a cause as well as a consequence
      of the visit, visiting the site of death may be an important part of the support
      offered to bereaved families after experiencing a disaster loss.

PMID- 24568000
TI  - Antidiabetic medicinal plants--between phytotherapy and lead structure research.

PMID- 24568001
TI  - Guest editorial: the pragmatic reality of clinical research.

PMID- 24568002
TI  - The Beech Brook Group Therapy Assessment tool: a pilot study.
AB  - BACKGROUND: Assessment is a critical component of therapeutic intervention as it
      serves as the basis from which clinical goals and objectives are derived.
      Unfortunately, there is a dearth of reliable group therapy assessment
      instruments, especially for children and preadolescents who have severe emotional
      disturbances. OBJECTIVE: The purpose of this study was to test reliability of a
      newly developed group therapy assessment instrument for use with children who
      have serious emotional disturbances that require placement in a residential or
      partial hospitalization treatment program. METHODS: After conducting an extensive
      literature review, the authors developed, refined, and tested a group therapy
      assessment tool for use in both music therapy and traditional therapy, measuring
      nine items: attention to task (physical and verbal), eye contact, pro-social
      skills (physical and verbal), empathy (physical and verbal), and managing
      negative affect (physical and verbal). Six participants with a mean age of 9.5
      (SD = 1.85) years were randomly selected to test the group therapy assessment
      tool from a pool of 60 eligible children receiving group partial hospitalization
      therapy. Participants were scored by three raters across two partial
      hospitalization therapy groups for inter-rater reliability. Content and construct
      validity were also examined. RESULTS: Intraclass Coefficients (ICC) averaged
      0.994 across all nine items indicating excellent inter-rater reliability. Content
      and construct validity was established and the instrument demonstrated good
      external validity potential. CONCLUSIONS: The Beech Brook Therapy Assessment
      Instrument has demonstrated excellent inter-rater reliability in measuring
      important behaviors of functioning central in the treatment of youth with severe
      and emotional disturbances. The measure has potential for wide utility and
      application in practice and research; however, future studies are needed to
      establish external validity.

PMID- 24568003
TI  - Viewers' perceptions of a YouTube music therapy session video.
AB  - BACKGROUND: Recent research revealed diverse content and varying levels of
      quality in YouTube music therapy videos and prompted questions about viewers'
      discrimination abilities. OBJECTIVE: This study compares ratings of a YouTube
      music therapy session video by viewers with different levels of music therapy
      expertise to determine video elements related to perceptions of representational
      quality. METHOD: Eighty-one participants included 25 novices (freshmen and
      sophomores in an introductory music therapy course), 25 pre-interns (seniors and
      equivalency students who had completed all core Music Therapy courses), 26
      professionals (MT-BC or MT-BC eligibility) with a mean of 1.75 years of
      experience, and an expert panel of 5 MT-BC professionals with a mean of 11 years
      of experience in special education. After viewing a music therapy special
      education video that in previous research met basic competency criteria and
      professional standards of the American Music Therapy Association, participants
      completed a 16-item questionnaire. RESULTS: Novices' ratings were more positive
      (less discriminating) compared to experienced viewers' neutral or negative
      ratings. Statistical analysis (ANOVA) of novice, pre-intern, and professional
      ratings of all items revealed significant differences p, .05) for specific
      therapy content and for a global rating of representational quality. Experienced
      viewers' ratings were similar to the expert panel's ratings. Content analysis of
      viewers' reasons for their representational quality ratings corroborated ratings
      of therapy-specific content. CONCLUSIONS: A video that combines and clearly
      depicts therapy objectives, client improvement, and the effectiveness of music
      within a therapeutic intervention best represent the music therapy profession in
      a public social platform like YouTube.

PMID- 24568004
TI  - A systematic review on the neural effects of music on emotion regulation:
      implications for music therapy practice.
AB  - BACKGROUND: Emotion regulation (ER) is an internal process through which a person
      maintains a comfortable state of arousal by modulating one or more aspects of
      emotion. The neural correlates underlying ER suggest an interplay between
      cognitive control areas and areas involved in emotional reactivity. Although some
      studies have suggested that music may be a useful tool in ER, few studies have
      examined the links between music perception/production and the neural mechanisms
      that underlie ER and resulting implications for clinical music therapy treatment.
      Objectives of this systematic review were to explore and synthesize what is known
      about how music and music experiences impact neural structures implicated in ER,
      and to consider clinical implications of these findings for structuring music
      stimuli to facilitate ER. METHODS: A comprehensive electronic database search
      resulted in 50 studies that met predetermined inclusion and exclusion criteria.
      Pertinent data related to the objective were extracted and study outcomes were
      analyzed and compared for trends and common findings. RESULTS: Results indicated
      there are certain music characteristics and experiences that produce desired and
      undesired neural activation patterns implicated in ER. Desired activation
      patterns occurred when listening to preferred and familiar music, when singing,
      and (in musicians) when improvising; undesired activation patterns arose when
      introducing complexity, dissonance, and unexpected musical events. Furthermore,
      the connection between music-influenced changes in attention and its link to ER
      was explored. CONCLUSIONS: Implications for music therapy practice are discussed
      and preliminary guidelines for how to use music to facilitate ER are shared.

PMID- 24568005
TI  - "Compassionate care is alive and well in the NHS".

PMID- 24568006
TI  - London hit worse by nurse shortage.

PMID- 24568007
TI  - Urgent care staffing concerns boil over into transparency row.

PMID- 24568008
TI  - Francis report leads trust to look for 80 more staff.

PMID- 24568009
TI  - Stockings recommended for ulcers.

PMID- 24568010
TI  - Super regulator to examine how nurse invents NMC handled mid staffs cases.

PMID- 24568011
TI  - NHS pension scheme to be open to private contract nursing staff.

PMID- 24568012
TI  - "MSPs will back patients first Scotland in raising concerns".

PMID- 24568013
TI  - "Slices of policy handed down from a distance won't restore nursing".

PMID- 24568014
TI  - "Blaming disadvantaged patients has no place in care".

PMID- 24568015
TI  - Physical and social causes hypothermia.
AB  - Hypothermia has a number of physical and social causes, particularly among older
      people. It is vital that nurses are aware of these risk factors. This article
      explores the causes of hypothermia, preventive measures, clinical signs and
      immediate treatment in the community.

PMID- 24568016
TI  - Should compassionate practice be incentivised?
AB  - A lack of compassion is often seen as the root of problems within the NHS.
      However, this assumption is open to question. It is not always clear what is
      meant by compassion, and it is not evident that compassion is the best way of
      motivating healthcare workers. Addressing organisational issues by attempting to
      enhance compassion may therefore mask the real cause of the problems the NHS
      currently faces.

PMID- 24568017
TI  - Subcutaneous immunoglobulin therapy home.
AB  - Subcutaneous immunoglobulin (SClg) replacement therapy is a new clinical service
      development in adult respiratory care undertaken at the Royal Brompton and
      Harefield Foundation Trust. SCIg therapy reduces appropriate patients'
      susceptibility to recurrent acute and chronic respiratory infections. Patients
      with specific chronic respiratory conditions and antibody deficiency can be
      treated with SCIg therapy at home, rather than with intravenous immunoglobulin
      (IVIg) therapy in hospital. Using a personalised teaching programme and managing
      the daily demands of the clinical service promotes greater concordance with
      treatment. With over 34% of our immunoglobulin therapy patients now on SCIg
      replacement therapy, this treatment innovation has brought about high levels of
      patient satisfaction and cost savings to trust budgets.

PMID- 24568018
TI  - Treating congenital adrenal hyperplasia.
AB  - Genettreating congenital adrenal hyperplasia.ic alterations associated with rare
      endocrine diseases disrupt the body's normal chemical communication system.
      Faulty genes can affect any part of the hormone pathway by altering the way the
      body recognises a hormone, or how a hormone acts on a target organ. One example
      is congenital adrenal hyperplasia. CAH results from an inherited alteration in a
      gene that blocks an essential enzyme (usually 21-hydroxylase) in the adrenal
      hormone pathway. Synthesis of cortisol (the "stress" hormone) and aldosterone,
      which regulates the blood pressure through sodium, potassium and fluid balance,
      is impaired or absent. The adrenal glands enlarge as they work harder to correct
      the imbalance, resulting in the overproduction of androgens (male hormones); the
      more severe the enzyme block, the greater the male hormone production. In 95% of
      people with CAH, it is due to an alteration in the 21-hydroxylase gene, which is
      recessively inherited (Perrin et al, 2000). One in 55 people is a carrier for CAH
      (Baumgartner-Parzer et al, 2005).

PMID- 24568019
TI  - What do nurses need to know about genetics?
AB  - This sixth article in our series on rare diseases explores the impact of a
      genetic diagnosis on patients and their families. As genomic testing becomes
      mainstream, practitioners need to understand the role of genetics in disease and
      know how to refer patients for help and advice.

PMID- 24568020
TI  - 60 seconds with Kate Jack.

PMID- 24568021
TI  - Making care special.

PMID- 24568022
TI  - Evaluating the output stability of LINAC with a reference detector using 3D water
      phantom.
AB  - We report the discovery of abnormal fluctuations in the output obtained when
      measuring a water phantom and adjustments that reduce these outliers. Using a
      newly developed three-dimensional scanning water phantom system, we obtained the
      depth dose and off-axis dose ratio required for the beam data of a medical linear
      accelerator (LINAC). The field and reference detectors were set such that the
      measured values could be viewed in real time. We confirmed the scanning data
      using the field detector and the change in the output using the reference
      detector while measuring by using the water phantom. Prior to output adjustment
      of the LINAC, we observed output abnormalities as high as 18.4%. With
      optimization of accelerator conditions, the average of the output fluctuation
      width was reduced to less than +/-0.5%. Through real-time graphing of reference
      detector measurements during measurement of field detector, we were able to
      rapidly identify abnormal fluctuations. Although beam data collected during
      radiation treatment planning are corrected for output fluctuations, it is
      possible that sudden abnormal fluctuations actually occur in the output.
      Therefore, the equipment should be tested for output fluctuations at least once a
      year. Even after minimization of fluctuations, we recommend determining the
      potential dose administered to the human body taking into account the width of
      the output fluctuation.

PMID- 24568023
TI  - [Development of the 60Co gamma-ray standard field for therapy-level dosimeter
      calibration in terms of absorbed dose to water (N(D,w))].
AB  - A primary standard for the absorbed dose rate to water in a 60Co gamma-ray field
      was established at National Metrology Institute of Japan (NMIJ) in fiscal year
      2011. Then, a 60Co gamma-ray standard field for therapy-level dosimeter
      calibration in terms of absorbed dose to water was developed at National
      Institute of Radiological Sciences (NIRS) as a secondary standard dosimetry
      laboratory (SSDL). The results of an IAEA/WHO TLD SSDL audit demonstrated that
      there was good agreement between NIRS stated absorbed dose to water and IAEA
      measurements. The IAEA guide based on the ISO standard was used to estimate the
      relative expanded uncertainty of the calibration factor for a therapy-level
      Farmer type ionization chamber in terms of absorbed dose to water (N(D,w)) with
      the new field. The uncertainty of N(D,w) was estimated to be 1.1% (k = 2), which
      corresponds to approximately one third of the value determined in the existing
      air kerma field. The dissemination of traceability of the calibration factor
      determined in the new field is expected to diminish the uncertainty of dose
      delivered to patients significantly.

PMID- 24568024
TI  - [Outline of Fukushima Daiichi Nuclear Power Plant accident].

PMID- 24568025
TI  - [Accidents of the Fukushima Daiichi Nuclear Power Plants and future].
AB  - A massive earthquake of magnitude 9 terribly happened far out at sea of Tohoku
      area on 11 March, 2011. After this earthquake the hugest tsunami in the history
      came to the hundreds km of the seashore of Tohoku area. Due to this tsunami all
      of the four nuclear power plants of Fukushima Daiichi lost every electric power
      and, soon after this, loss nuclear fuels from number 1 to 3 reactors melt through
      their power containers. According to this phenomena, large amount of the radio
      activities have been released in the air. There were some releases but major
      contaminations happened at the time of the two releases in the morning of 15
      March, 2011. Due to this, to the direction of the northwest until the Iitate
      Village over 30km zone was contaminated. In this paper I explain the time course
      of the accidents and that how contaminated.

PMID- 24568026
TI  - [How to understand low dose risks].
AB  - It is well established that those who were exposed to ionizing radiation have
      increased risks of developing malignancies. The magnitude of the risk varies
      depending on not only the dose but also age at the time of exposure, gender,
      background incidence rate etc. In the case of atomic bomb survivors, the relative
      risk of cancer is linearly related to the dose, and the sex averaged relative
      risk (exposure age is 30, risk calculation is when they reached age 70) is 1.5 at
      1 Gy. Because the increased risks below 100 to 200 mGy are too small and not
      statistically significant, there are arguments in interpreting the risks at the
      low dose range.

PMID- 24568027
TI  - [Ethics and regulation of clinical research].
AB  - We explained the spirit of the clinical research guideline and the present
      condition of the clinical research in Japan. And then, the responsibility of the
      principal investigators was described.

PMID- 24568028
TI  - [Researchers driven by 'seeds' verus those driven by 'needs'].

PMID- 24568029
TI  - Symbiogenesis: the holobiont as a unit of evolution.
AB  - Symbiogenesis is the result of the permanent coexistence of various bionts to
      form the holobiont (namely, the host and its microbiota). The holobiome is the
      sum total of the component genomes in a eukaryotic organism; it comprises the
      genome of an individual member of a given taxon (the host genome) and the
      microbiome (the genomes of the symbiotic microbiota). The latter is made up of
      the genes of a variety of microbial communities that persist over time and are
      not eliminated by natural selection. Therefore, the holobiome can also be
      considered as the genomic reflection of the complex network of symbiotic
      interactions that link an individual member of a given taxon with its associated
      microbiome. Eukaryotic individuals can be analyzed as coevolved, tightly
      integrated, prokaryotic communities; in this view, natural selection acts on the
      holobiont as if it were an integrated unit. The best studied holobionts are those
      that emerged from symbioses involving insects. The presence of symbiotic
      associations throughout most of the evolutionary history of insects suggests that
      they were a driving force in the diversification of this group. Support for the
      evolutionary importance of symbiogenesis comes from the observation that the
      gradual passage from an ancestral to a descendant species by the accumulation of
      random mutations has not been demonstrated in the field, nor in the laboratory,
      nor in the fossil record. Instead, symbiogenesis expands the view of the point
      mutation-only as the unique mechanisms of evolution and offers an explanation for
      the discontinuities in the fossil record ("punctuated equilibrium"). As such, it
      challenges conventional paradigms in biology. This review describes the
      relationships between xylophagous insects and their microbiota in an attempt to
      understand the characteristics that have determined bacterial fidelity over
      generations and throughout evolutionary history.

PMID- 24568030
TI  - Non-developing ascospores in apothecia of asexually reproducing lichen-forming
      fungi.
AB  - The presence of apothecia in mixed species (vegetatively reproducing lichens,
      occasionally producing ascomata) has been interpreted as a mechanism to increase
      genetic variability in mostly clonal populations. However, spore viability from
      these apothecia has not been studied. We asked whether ascospores of the mixed
      species Physconia grisea are viable and thereby contribute to increasing the
      genetic diversity within populations of this species. An ontogenetic study of
      spores in cultures of P. grisea and a related sexual species (P. distorta),
      showed that although mature apothecia from both species produced and discharged
      meiospores capable of germination, spores from P. grisea were only rarely (0.43%)
      able to continue development whereas those from P. distorta germinated and
      developed successfully. The strongly reduced viability of P. grisea spores
      suggested that they do not have a strong reproductive function, at least in the
      two local populations analyzed. Additionally, we show that the segregation of
      Physconia grisea ssp. lilacina does not have molecular support.

PMID- 24568031
TI  - Identification of rhizobial strains nodulating Egyptian grain legumes.
AB  - Fifty four bacterial strains were isolated from root nodules of the grain legumes
      Cicer arietinum, Lens esculentus, Phaseolus vulgaris, Pisum sativum, and Vicia
      faba grown in cultivated lands of Beni-Suef Governorate (Egypt). Repetitive
      extragenic palindromic (REP)-polymerase chain reaction (PCR) clustered the
      strains into 15 REP-PCR groups. The nearly complete sequence of the 16S rRNA gene
      from a representative strain of each REP-PCR pattern showed that the strains were
      closely related to members of the family Rhizobiaceae of the Alphaproteobacteria.
      Pairwise alignments between globally aligned sequences indicated that the strains
      from V. faba had 99.6% identity with Rhizobium leguminosarum, and those from P.
      vulgaris 99.76% and 100% with sequences from R. leguminosarum and R. mesosinicum,
      respectively. Strains from P. sativum had 99.76%, 99.84%, and 99.92% sequence
      identity with R. leguminosarum, R. etli, and R. pisi, respectively, and those
      from L. esculentus had 99.61% identity with sequences from R. leguminosarum.
      Sequences of the strains from C. arietinum had 100% identity with those of
      Mesorhizobium amorphae and M. robiniae, respectively. Nitrogenase activity,
      determined as acetylene-dependent ethylene production, was detected in nodules
      formed after inoculation of the corresponding host plant with the representative
      rhizobial species.

PMID- 24568032
TI  - Characterization of the gene cluster involved in allantoate catabolism and its
      transcriptional regulation by the RpiR-type repressor HpxU in Klebsiella
      pneumoniae.
AB  - Bacteria, fungi, and plants have metabolic pathways for the utilization of
      nitrogen present in purine bases. In Klebsiella pneumoniae, the genes responsible
      for the assimilation of purine ring nitrogen are distributed in three separated
      clusters. We characterized the gene cluster involved in the metabolism of
      allantoate (genes KPN_01761 to KPN_01771). The functional assignments of HpxK, as
      an allantoate amidohydrolase, and of HpxU, as a regulator involved in the control
      of allantoate metabolism, were assessed experimentally. Gene hpxU encodes a
      repressor of the RpiR family that mediates the regulation of this system by
      allantoate. In this study, the binding of HpxU to the hpxF promoter and to the
      hpxU-hpxW intergenic region containing the divergent promoter for these genes was
      evidenced by electrophoretic mobility shift assays. Allantoate released the HpxU
      repressor from its target operators whereas other purine intermediate
      metabolites, such as allantoin and oxamate, failed to induce complex
      dissociation. Sequence alignment of the four HpxU identified operators identified
      TGAA-N8-TTCA as the consensus motif recognized by the HpxU repressor.

PMID- 24568034
TI  - A modular reactor to simulate biofilm development in orthopedic materials.
AB  - Surfaces of medical implants are generally designed to encourage soft- and/or
      hard-tissue adherence, eventually leading to tissue- or osseo-integration.
      Unfortunately, this feature may also encourage bacterial adhesion and biofilm
      formation. To understand the mechanisms of bone tissue infection associated with
      contaminated biomaterials, a detailed understanding of bacterial adhesion and
      subsequent biofilm formation on biomaterial surfaces is needed. In this study, a
      continuous-flow modular reactor composed of several modular units placed in
      parallel was designed to evaluate the activity of circulating bacterial
      suspensions and thus their predilection for biofilm formation during 72 h of
      incubation. Hydroxyapatite discs were placed in each modular unit and then
      removed at fixed times to quantify biofilm accumulation. Biofilm formation on
      each replicate of material, unchanged in structure, morphology, or cell density,
      was reproducibly observed. The modular reactor therefore proved to be a useful
      tool for following mature biofilm formation on different surfaces and under
      conditions similar to those prevailing near human-bone implants.

PMID- 24568035
TI  - Gold or green: the debate on open access policies.
AB  - The movement for open access to science seeks to achieve unrestricted and free
      access to academic publications on the Internet. To this end, two mechanisms have
      been established: the gold road, in which scientific journals are openly
      accessible, and the green road, in which publications are self-archived in
      repositories. The publication of the Finch Report in 2012, advocating exclusively
      the adoption of the gold road, generated a debate as to whether either of the two
      options should be prioritized. The recommendations of the Finch Report stirred
      controversy among academicians specialized in open access issues, who felt that
      the role played by repositories was not adequately considered and because the
      green road places the burden of publishing costs basically on authors. The Finch
      Report's conclusions are compatible with the characteristics of science
      communication in the UK and they could surely also be applied to the (few)
      countries with a powerful publishing industry and substantial research funding.
      In Spain, both the current national legislation and the existing rules at
      universities largely advocate the green road. This is directly related to the
      structure of scientific communication in Spain, where many journals have little
      commercial significance, the system of charging a fee to authors has not been
      adopted, and there is a good repository infrastructure. As for open access
      policies, the performance of the scientific communication system in each country
      should be carefully analyzed to determine the most suitable open access strategy.

PMID- 24568033
TI  - Phylogenetic characterization and quantification of ammonia-oxidizing archaea and
      bacteria from Lake Kivu in a long-term microcosm incubation.
AB  - A microcosm cultivation-based method was set up to investigate the growth of
      ammonia-oxidizing archaea (AOA), isolated from a water sample acquired at a depth
      of 50 m from the northern basin of Lake Kivu. For this purpose, both CARD-FISH
      and qPCR targeting of archaeal 16S rRNA and amoA genes were used. Archaeal cell
      growth at the end of the 246-day microcosm experiment accounted for 35% of the
      SybrGold-stained cells, which corresponded to 6.61 x 10(6) cells/ml and 1.76 +/-
      0.09 x 10(6) archaeal 16S rRNA gene copies/ml. Clone libraries and DGGE
      fingerprinting confirmed the dominance of AOA phylotypes in the archaeal
      community microcosm. The majority of the identified archaeal 16S rRNA gene
      sequences in the clone libraries were affiliated with Thaumarchaeota Marine Group
      1 .1a. Subsequent cultivation of the AOA community on deep-well microtiter plates
      in medium containing different carbon sources to stimulate archaeal growth failed
      to show significant differences in archaeal abundance (ANOVA t14 = -1.058, P =
      0.308 and ANOVA t14= 1.584, P = 0.135 for yeast extract and simple organic acids,
      respectively). The lack of growth stimulation by organic compounds is in
      concordance with the oligotrophic status of Lake Kivu. Finally, the addition of
      antibiotics to the growth medium resulted in archaeal cell counts that were
      significantly lower than those obtained from cultures in antibiotic-free medium
      (ANOVA t14 = 12.12, P < 0.001).

PMID- 24568036
TI  - [Current status of and regional differences in CKD management and medical
      cooperation in Japan: from the results of a nationwide questionnaire survey for
      primary care physicians].
AB  - OBJECTIVE: The goal of this study was to figure out the current status of and
      regional differences in CKD management and medical cooperation in Japan. METHODS:
      We conducted a nationwide questionnaire survey on CKD management for primary care
      physicians (PCPs) from December 2012 to March 2013. The questionnaire included 36
      items about CKD management and medical cooperation. In order to compare the
      current status of CKD care and cooperation, we divided the country into 11 areas;
      Hokkaido, Tohoku, Kanto, Koshin-etsu, Hokuriku, Chubu-Tokai, Kinki, Chugoku,
      Shikoku, Kyushu and Okinawa. RESULTS: 28,200 sets of questionnaires were
      delivered to PCPs throughout Japan, and 2,287 (8.1%) doctors responded. Doctors
      at clinics accounted for 86.5%, and 90.9% were non-nephrologists. Regional
      differences were evident in the following items regarding CKD management;
      urinalysis at the first examination, measurement of urinary protein/albumin
      excretion, frequency of blood testing, counselling with eGFR, prescription of
      erythropoiesis stimulating agents (ESA). Urinalysis at the first examination was
      relatively rare in Koshin-etsu and Kanto (p < 0.01), and counseling with eGFR was
      relatively rare in Tohoku, Shikoku and Koshin-etsu (p = 0.05). Regional
      differences regarding medical cooperation were evident in the following items;
      functional level of cooperation, critical path, presence of consulting
      nephrologist, personal relationship, satisfaction with the nephrologists'
      reaction to referral, CKD involvement in Specific Medical Checkup/Specific
      Medical Guidance. Functional level of cooperation was higher in Chugoku, Okinawa,
      Chubu-Tokai and Hokuriku, and lower in Shikoku, Koshin-etsu and Kinki (p < 0.05).
      Serum creatinine measurement in the Specific Medical Checkup was involved more
      frequently in Okinawa, Shikoku, Kanto, Chubu-Tokai, Kyushu and Hokuriku, and less
      frequently in Tohoku, Chugoku and Kinki (p < 0.01). CONCLUSION: We elucidated the
      current status of CKD management by PCPs and medical cooperation in Japan.
      Effective actions to improve CKD care must be proposed on the basis of these
      data, especially the existing regional differences.

PMID- 24568037
TI  - [Influence of physicians' subspecialty and training history on CKD management and
      medical cooperation: from the results of a nationwide questionnaire survey for
      primary care physicians].
AB  - OBJECTIVE: The goal of this study was to elucidate how the subspecialty and
      training history of primary care physicians(PCPs) influence CKD management and
      medical cooperation in Japan. METHODS: We conducted a nationwide questionnaire
      survey on CKD management for PCPs from December 2012 to March 2013. The
      questionnaire included 32 items about CKD management and medical cooperation.
      PCPs' subspecialties were categorized as follows: general internal medicine,
      nephrology, cardiology, diabetology/endocrinology, gastroenterology, pulmonology,
      neurology, neurosurgery, hematology, collagen disease/rheumatology, allergology.
      The PCPs' training history of nephrology was classified into three categories:
      none, experienced, active-nephrologist. Response distributions for each question
      were compared between the PCPs' subspecialties and the three categories of
      training history. RESULTS: 2,287 out of 28,200 PCPs (8.1%) of all 47 prefectures
      responded. The majority (86.5%) of responders were PCPs at clinics, and 90.9%
      were non-nephrologists. The PCPs' subspecialty influenced the response
      distributions in the following questions: utilization of the CKD guidebook,
      urinalysis at the first and follow-up examinations, frequency of blood testing,
      counselling with eGFR, self-monitoring of blood pressure, prescription and
      cessation of renin-angiotensin system (RAS) inhibitors, anemia treatment with
      erythropoiesis stimulating agents (ESA). The PCPs' training history of nephrology
      had a strong impact on various aspects of CKD management. The PCPs'
      subspecialties also influenced the responses regarding medical cooperation of
      CKD: relationship with nephrologists, utilization of critical path, criterion of
      patient referral, requests for nephrologists, discontent with the nephrologists'
      response. CONCLUSION: We elucidated that the PCPs' subspecialty and training
      history of nephrology substantially influenced CKD management and medical
      cooperation in Japan. Effective promotion activities to improve CKD management
      and medical cooperation should be proposed on the basis of these data.

PMID- 24568038
TI  - [Granulomatous interstitial nephritis in a patient with Behcet's disease treated
      with infliximab].
AB  - The patient is a 41-year-old man diagnosed with uveitis in 2004. Although the
      patient was positive for HLA-B51, the primary disease could not be identified,
      and oral administration of prednisolone (PSL) was initiated. A subsequent gradual
      decrease in the PSL dose was accompanied by the development of recurrent
      spasmodic chorioretinopathy and hypopyon. In November 2007, the patient was
      diagnosed with Behcet's disease based on the findings of erythema nodosum,
      acneiform eruption, and oral aphtha. In order to control the ocular symptoms,
      infliximab was administered. However, the patient's renal function began to
      deteriorate in November 2011, and he was transferred to our department after 6
      months. At that time, his creatinine level was 8.56 mg/dL. Renal biopsy
      examination revealed granulomatous interstitial nephritis. Moreover, only
      infliximab yielded a positive result in a drug-induced lymphocyte stimulation
      test (DLST). Following initiation of PSL administration at 60 mg/day, his renal
      function improved. His creatinine level remained constant at approximately 3
      mg/dL. In the present case, Behcet's disease, sarcoidosis, and infection were
      excluded as the underlying disease causing granulomatous interstitial nephritis.
      Moreover, infliximab is reportedly involved in the development of granulomas.
      Recent reports have stated that administration of TNF-alpha inhibitors
      occasionally results in the development of granulomas in the lungs and skin, and
      sometimes, in the kidneys as well. When renal dysfunction occurs in patients
      receiving TNF-alpha inhibitors, we believe that it is essential to include
      adverse events associated with TNF-alpha inhibitors in the differential
      diagnoses.

PMID- 24568039
TI  - Practice and perceptions of obstetrics and gynecology providers and the treatment
      of overweight and obese women.
AB  - OBJECTIVE: To verify how frequently obstetrics-gynecology providers documented
      the diagnosis and treatment of overweight/obese patients during routine
      examinations. These results were compared to a survey administered to this group
      of providers that measured their perceived practice patterns regarding weight
      management. STUDY DESIGN: A retrospective chart review was performed of well
      woman and routine postpartum exams of patients with a body mass index (BMI) > 25.
      Patient encounters were reviewed for a diagnosis of overweight or obese and
      weight management interventions offered. In addition, a survey was administered
      to obstetrics-gynecology providers who performed these exams in order to measure
      their perceived obesity diagnosis and treatment patterns. RESULTS: A total of
      1,145 patient encounters were reviewed of patients with a BMI > 25. Providers
      documented 77 of the 1,145 (6.7%) as overweight or obese. Only 70 of 1,145 (6.1%)
      had documented interventions (i.e., recommending weight loss or exercise). In
      contrast, a majority of providers surveyed reported they appropriately diagnosed
      and counseled patients with obesity. CONCLUSION: The majority of obstetrics and
      gynecology providers surveyed perceived that weight management was an important
      part of their clinical practice; however documentation of patient encounters did
      not match their perceived clinical

PMID- 24568040
TI  - Endometriosis-associated ovarian malignancy: a retrospective analysis of
      presentation, treatment, and outcome.
AB  - OBJECTIVE: To investigate the relationship of age and tumors associated with
      endometriosis and outcome of different histologies of epithelial ovarian cancer
      arising from endometriosis. STUDY DESIGN: We identified cases of epithelial
      ovarian cancers with clear cell, endometrioid, or mixed clear cell and
      endometrioid histologies from January 2001 to March 2009. Tumors were classified
      as either "arising in" endometriosis, "associated with" endometriosis or
      "controls" (not associated with endometriosis). We collected information
      regarding patient demographics, past medical history, presentation at diagnosis,
      treatment, and outcome. RESULTS: Of 140 patients identified, 42 (30.0%) had clear
      cell, 92 (65.7%) had endometrioid, and 6 (4.3%) had mixed. Of those, 28.6% of
      tumors were associated with endometriosis (n = 40), 37.1% were arising in
      endometriosis (n = 52), and 34.3% were controls (n = 48). Premenopausal women had
      tumors that were more likely arising from or associated with endometriosis as
      compared to tumors in postmenopausal women (p = 0.005). Premenopausal patients
      were also more likely to present with early stage disease as compared to
      postmenopausal women (80.4% vs. 63.6%, p = 0.04) and better overall survival (p <
      0.008). Survival analyses of the entire cohort showed that improved survival was
      associated with stage (p < 0.001), grade (p < 0.001), endometrioid histology (p <
      0.005), and with tumors associated with or arising in endometriosis (p < 0.04).
      Multivariate analysis controlling for menopausal status showed the presence of
      endometriosis was no longer associated with a survival advantage (p = 0.08).
      CONCLUSION: The association with endometriosis does appear, at least in
      endometrioid tumors, to provide a survival benefit. Overall, menopausal status,
      stage, and grade are more powerful variables associated with improved survival.

PMID- 24568041
TI  - Embryonic soluble human leukocyte antigen-G as a marker of embryo competency in
      assisted reproductive technology for Chinese women.
AB  - OBJECTIVE: To investigate whether embryonic soluble human leukocyte antigen-G
      (sHLA-G) could be a noninvasive marker for embryo competency in assisted
      reproductive technology (ART), which is still controversial due to the different
      detection assays used and the different culture conditions in laboratories. STUDY
      DESIGN: Based on the standardization of IVF procedures and the embryo culture
      condition, a total of 205 embryo culture supernatants (ESs) from 92 ART cycles
      were evaluated for sHLA-G contents by chemiluminescent ELISA assay. RESULTS: sHLA
      G presence could be detected in 30.7% of the ESs tested. In the cycles where at
      least one of the embryos transferred was positive for sHLA-G, 51.9% of patients
      (27/52) achieved a clinical pregnancy. In cycles where none of the embryos
      transferred secreted detectable amounts of sHLA-G, the pregnancy rate was only
      30.0% (12/40, p < 0.05). The implantation rate in sHLA-G-positive cycles was also
      significantly higher (31.5%) than that in sHLA-G-negative cycles (14.9%, p <
      0.05). CONCLUSION: The results suggested sHLA-G in ESs as a potential marker of
      embryo competency in ART programs for the Chinese population.

PMID- 24568042
TI  - Good fertilization results associated with high IL-1beta concentrations in
      follicular fluid of IVF patients.
AB  - OBJECTIVE: To determine the levels of interleukin-1 beta (IL-1beta) in follicular
      fluid and embryo culture fluid after controlled ovarian hyperstimulation and to
      assess the association of this cytokine with the outcome of in vitro
      fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatment and
      embryo transfer. STUDY DESIGN: A total of 256 couples undergoing the IVF/ICSI
      program were included in this prospective study. Zygote quality, embryo and
      blastocyst morphology were evaluated, and embryo transfer was performed 5 days
      after oocyte recovery. IL-1beta concentrations were measured in follicular fluid
      and embryo culture fluid of the third and fifth culture days. RESULTS: Embryo
      replacement was performed with a median of 2 embryos per cycle. In all, 44
      clinical pregnancies were achieved in 256 assisted reproductive technology (ART)
      cycles (pregnancy rate: 19.8% per transfer). Follicular fluid concentrations of
      IL-1P were not significantly different in pregnant (2.1 pg/mL) and nonpregnant
      women (2.7 pg/mL). Follicular fluid of lVF, but not ICSI, patients with good
      fertilization rates (> 90%) contained significantly higher levels of IL-1beta
      (3.3 pg/ mL) than did follicular fluid of women with fertilization rates < or =
      90% (2.0 pg/mL, p < 0.05). No correlation was found between intrafollicular IL
      1beta and zygote morphology, day 3 and day 5 embryo morphology. There was no
      relationship between IL-1beta in culture fluid supernatants and embryonic
      development. CONCLUSION: In IVF patients high levels of intrafollicular IL-1beta
      were associated with good fertilization rates. There seems to be no correlation
      between IL-1beta concentrations in follicular fluid or embryo culture fluid and
      embryo morphology or pregnancy outcome of ART cycles.

PMID- 24568043
TI  - Polycystic ovary syndrome: association of a C/T single nucleotide polymorphism at
      tyrosine kinase domain of insulin receptor gene with pathogenesis among lean
      Japanese women.
AB  - OBJECTIVE: To assess whether the insulin receptor (INSR) gene contributes to
      genetic susceptibility to polycystic ovary syndrome (PCOS) in a Japanese
      population. STUDY DESIGN: We ex-amined the frequency of the His 1058 C/T single
      nucleotide polymorphism (SNP) found in exon 17 of the INSR gene in 61 Japanese
      PCOS patients and 99 Japanese healthy controls. In addition, we analyzed the
      association between the genotype of this SNP and the clinical phenotypes.
      RESULTS: The frequency of the C/C genotype was not significantly different
      between all PCOS patients (47.5%) and controls (35.4%). However, among the lean
      cases (body mass index < or = 20 kg/m2) the frequency of the C/C genotype was
      significantly increased (p < 0.05) in PCOS patients (65.0%) as compared with
      controls (36.6%). CONCLUSION: We concluded that the His 1058 C/T polymorphism at
      the tyrosine kinase domain of the INSR gene had a relationship to the
      pathogenesis of lean PCOS patients in a Japanese population.

PMID- 24568044
TI  - Effect of obesity on perioperative outcomes of laparoscopic hysterectomy.
AB  - OBJECTIVE: To compare the effect of obesity on perioperative outcomes in women
      undergoing laparoscopic hysterectomy. STUDY DESIGN: In this retrospective cohort
      study, perioperative outcomes of all women who underwent laparoscopic
      supracervical hysterectomy (LSH) or total laparoscopic hysterectomy (TLH) for
      benign conditions were compared between obese (body mass index > or = 30 kg/m2)
      and nonobese women. RESULTS: Baseline characteristics were similar between 320
      (33.0%) obese and 550 (67%) nonobese women except for race and the rates of
      hypertension and diabetes. The adjusted rates of urinary tract injury, vaginal
      cuff dehiscence, postoperative fever, and ileus were similar between the groups.
      For obese women, however, bleeding requiring transfusion was almost 3-fold (3.1
      vs. 1.1%, adjusted odds ratio [AOR] 2.93, 95% confidence interval [CI] 1.10-7.80)
      and laparotomy risk was approximately 2-fold (7.5 vs. 3.5%, AOR 2.35, 95% CI 1.30
      4.24) increased. The rate of urinary tract injury was 3.2% when obese women had
      TLH, but it was 0.3% for LSH performed on nonobese women. Of all 7 cuff
      dehiscences, 5 (71%) occurred in nonobese women undergoing TLH. CONCLUSION:
      Obesity increased the risk of bleeding requiring transfusion and conversion to
      laparotomy but did not influence the other perioperative complications. On
      subgroup analysis, LSH in nonobese women seems to result in best outcomes.

PMID- 24568045
TI  - Prevalence of myofascial chronic pelvic pain and the effectiveness of pelvic
      floor physical therapy.
AB  - OBJECTIVE: To determine the prevalence of myofascial pain and the outcome of
      transvaginal pelvic floor physical therapy for the treatment of chronic pelvic
      pain caused by myofascial pelvic pain in a tertiary care facility. STUDY DESIGN:
      A retrospective chart review was performed on all women who presented to our
      facility between January 2005 and December 2007. Those diagnosed with myofascial
      pelvic pain and referred for transvaginal pelvic floor physical therapy over this
      3-year period were evaluated. Participants with an initial pain score of > or =
      4, myofascial pelvic pain on examination, and who attended 2 or more physician
      visits were included in the analysis. Patient physical examination findings,
      symptoms, and verbal pain ratings were reviewed. RESULTS: In all, 146 (13.2%) of
      1,106 initially screened patients were diagnosed with myofascial pain. Seventy
      five (51%) of the 146 patients who were referred for physical therapy were
      included, and 75% had an initial pain score of > or = 7. Pain scores
      significantly improved proportional to the number of physical therapy visits
      completed, with 63% of patients reporting significant pain improvement.
      CONCLUSION: Transvaginal physical therapy is an effective treatment for chronic
      pelvic pain resulting from myofascial pelvic pain.

PMID- 24568047
TI  - Effect of embryo vitrification on postnatal mouse uterine development.
AB  - OBJECTIVE: To determine whether the process of vitrification affects the
      development of the female Mullerian duct. STUDY DESIGN: We examined the
      difference in morphology and gene expression of the developing uteri of 30 female
      mice from transferred vitrified embryos and 30 female mice from transferred fresh
      embryos. RESULTS: By employing histology, the data showed that there were no
      significant differences between the 2 groups of the same age. With the use of
      reverse transcription polymerase chain reaction and Western blotting, the data
      showed that there was no significant change in the expression of Wnt genes (Wnt4,
      Wnt5a, Wnt7a), beta-catenin/TCF target genes, and homeobox A10 (HOXA10) gene
      during uterine development in the vitrified group as compared with the control
      group. CONCLUSION: These data suggest that vitrifying preimplantation embryos may
      have no effects on morphology and gene expression of the uterus of offspring.

PMID- 24568048
TI  - How do patients use email to communicate with their doctor?
AB  - OBJECTIVE: To evaluate unsolicited email sent from patients to a general
      obstetrician-gynecologist. STUDY DESIGN: A retrospective review was performed of
      60 unsolicited emails sent to an obstetrician-gynecologist. Time sent, content,
      and physician response were evaluated. RESULTS: Most emails were sent during
      office hours. Fifty-four percent of the emails had content related to gynecologic
      issues. Twenty-seven percent of the emails had content related to obstetrical
      concerns. Nineteen percent of emails were nonclinical in nature. Fourteen percent
      of emails required a follow-up phone call. Twenty-nine percent of emails
      necessitated an office visit. CONCLUSION: Patients did not use email for
      emergency communication. The participating physician was pleased with the ease of
      responding to patients, especially while away from the office.

PMID- 24568046
TI  - Effect of vitamin D on postoperative adhesion formation in a rat uterine horn
      adhesion model.
AB  - OBJECTIVE: To determine the role of vitamin D for preventing or reducing
      postoperative adhesions. STUDY DESIGN: The uterine horn adhesion model was
      carried out in 24 female Wistar rats. The animals were randomized into 4 groups:
      (1) control, (2) Ringer's lactate, (3) olive oil, and (4) vitamin D. Adhesion
      grade and histologic findings of adhesion-carrying tissues were evaluated, and
      groups were compared according to these parameters. RESULTS: Rats treated with
      vitamin D had less adhesion and lower inflammation grade when compared to the
      control and Ringer's lactate groups, and the results were statistically
      significant (p < 0.05). On the other hand, no difference was detected between the
      groups according to the fibrosis score. CONCLUSION: Vitamin D decreased
      postsurgical adhesion scores by both visual scores and histologic analyses in a
      rat model. Further experimental and clinical trials are required to confirm these
      results.

PMID- 24568049
TI  - Delayed childbearing: determining responsibilities for prime gamete quality.
AB  - Delayed parenting affects fertility in women and in men, and cryopreservation of
      oocytes and sperm is becoming the latest trend as a solution for those who want
      or need to postpone procreation, in an attempt to avoid the damage medical
      conditions or time itself produces in gametes. Although "social freezing" is
      considered legitimate, its ethical and social aspects are in need of an overdue
      medical, public and legal debate. Assisted reproduction and cryopreservation, in
      combination with womb outsourcing, have opened the door to biological ectogenesis
      and the subsequent question of whether delayed childbearing means we should
      formally separate procreation from sexual activity. This article briefly
      summarizes what cryotechniques are capable of presently and in the near future,
      to separate fact from fiction. It names the implications for and discusses the
      practically virgin subject of the underlying responsibilities of delayed
      parenting techniques towards the child-to-be-not only the unborn but also the not
      yet-conceived child. Considering the medical, economic, legal and social
      consequences of these rapidly growing developments in reproduction, several
      reasons point at the need to formally separate procreation from sexual activity,
      specifying responsibilities in the first while respecting personal choice in the
      second.

PMID- 24568050
TI  - First successful delivery in Texas using vitrified human oocytes: a case report.
AB  - BACKGROUND: Successful pregnancies from cryopreserved oocytes are rare, but
      oocyte vitrification holds great promise for women in need of preserving their
      fertility due to illnesses that require treatments such as chemotherapy or
      radiation which cause irreversible depletion of ovarian reserve. The technique
      may also eventually be beneficial to women who wish to delay pregnancy to pursue
      educational and professional goals. Attempts at oocyte cryopreservation have
      until recently been quite disappointing due to three main problems: (1) high
      water content and intracellular ice crystal formation upon freezing and
      subsequent meiotic spindle damage, (2) zona pellucida hardening during
      cryopreservation and thus difficulty with subsequent fertilization and (3) the
      relatively large size of the cell and thus an unfavorable surface-to-volume ratio
      for equilibrium of solutes. These roadblocks have been gradually overcome by the
      use of improved cryoprotectants, intracytoplasmic sperm injection for
      fertilization, and the replacement of sodium in freezing media with an osmolyte.
      The net effect has been a substantial increase in oocyte survival and viability
      after cryopreservation. CASE: We report the first live births in Texas using
      vitrified oocytes. CONCLUSION: Vitrification may serve as a useful tool in the
      preservation of oocytes for women who wish to delay child bearing for medical or
      social reasons.

PMID- 24568051
TI  - Naturally occurring heterotopic pregnancy in a multiparous patient: a case
      report.
AB  - BACKGROUND: Heterotopic pregnancy, or simultaneous intrauterine and extrauterine
      pregnancy, occurs rarely. Consequently, clinicians might not always consider a
      diagnosis of heterotopic pregnancy. Transvaginal ultrasound or other imaging
      modalities cannot be completely relied upon to exclude heterotopic pregnancy from
      the differential diagnosis of pregnant patients with abdominal pain. CASE: A 32
      year-old woman, G5 P3105, presented to the emergency room with acute onset of
      diffuse abdominal pain. Ultrasound demonstrated an approximately 8-week
      intrauterine pregnancy. The patient underwent exploratory laparotomy for
      suspected torsion of a right ovarian cyst. Repeat exploratory laparotomy was
      required due to symptomatic anemia. The patient underwent exploratory laparotomy
      and right salpingo-oophorectomy. Pathology results demonstrated a right tubal
      ectopic pregnancy. CONCLUSION: Surgical and medical options exist for heterotopic
      pregnancy management. Despite negative heterotopic pregnancy results for
      transvaginal ultrasound, the possibility of heterotopic pregnancy should remain
      within the differential diagnosis of any pregnant patient with either natural or
      assisted reproduction technology intrauterine pregnancy who presents with
      abdominal pain and/or clinical signs of ectopic pregnancy.

PMID- 24568052
TI  - Pemphigoid gestationis with postpartum flare-up: a case report.
AB  - BACKGROUND: Pemphigoid gestationis (PG), also known as herpes gestationis, is an
      uncommon autoimmune blistering disease that almost always occurs in the third
      trimester of pregnancy. The sudden emergence of the disease, its clinical
      appearance and the course create great stress on the pregnant woman and the
      fetus. The disease has been associated with premature delivery and small-for
      gestational-age infants. Corticosteroids remain the mainstay of therapy. CASE: A
      pregnant woman presented with a diffuse blistering and intensely pruritic
      urticarial plaques that occurred periumbilically and spread to the rest of the
      body. We report a well-documented case of PG and an overview of the current
      understanding of the disease. CONCLUSION: A multidisciplinary approach for
      diagnosis, treatment and course of the disease from both dermatologic and
      gynecologic viewpoints is suggested.

PMID- 24568053
TI  - Cornual pregnancy after surgical treatment of an incarcerated fallopian tube: a
      case report.
AB  - BACKGROUND: Incarceration of the fallopian tube is a rare condition. Symptoms are
      often misleading, making proper diagnosis difficult because of nonspecific
      clinical presentations. We report a case of cornual pregnancy occurring 7 months
      after the treatment of an incarcerated fallopian tube. We believe that the
      abnormal cornual implantation of the gestational sac was due to myometrial
      reconstruction of the uterine wall. CASE: A primigravid woman treated for the
      incarceration of a fallopian tube was subsequently found to have a cornual
      pregnancy in a septate uterus. The cornual pregnancy was successfully aborted
      after laparoscopic myometrial reconstruction, and a metroplasty allowed a
      subsequent pregnancy. CONCLUSION: This hazardous type of ectopic pregnancy can be
      managed with systemic administration of methotrexate. If the cornual pregnancy is
      correctly identified at an early stage, this medical management can be attempted
      and offers the potential advantage of avoiding surgery and increasing the
      likelihood of preserving fertility.

PMID- 24568055
TI  - Orbital cellulitis: clinical course and management challenges. the Lagos State
      University Teaching Hospital experience.
AB  - BACKGROUND: Orbital cellulitis is a devastating acute infection of orbital soft
      tissues located posterior to the orbital septum. It is both vision and life
      threatening. It is an ocular emergency which most often present in childhood.
      OBJECTIVE: This article reviewed cases presenting during the study period with
      the view of examining the pattern of presentation, clinical course and management
      challenges. METHODS: A retrospective study was conducted on patients presenting
      with orbital cellulitis between January 2008 and June 2011. Socio-demographic
      data, entry and discharge visual acuity, presenting complaints, predisposing
      factors, duration of complaints, admission period and complications were
      extracted from clinical records and analyzed. RESULTS: Seventeen (17) patients
      presented with orbital cellulitis constituting 6.2% of ocular emergency
      admissions during the study period. Twelve (70.6%) were males. Thirteen (76.5%)
      were children. The major predisposing factors were upper respiratory tract
      infections, and facial and globe injuries in five (22.7%) cases respectively.
      Only five (29.4%), presented within three days of disease onset. Average duration
      of admission was 10.6 days. Complications during the course of disease were
      category 4 and 5 blindness in five (23.5%), orbital abscess four (23.5%),
      cavernous sinus thrombosis two (11.8%), contralateral preseptal cellulitis two
      (11.8%) and exposure keratopathy in one (5.9%). CONCLUSION: Orbital cellulitis
      has remained a disease with high ocular morbidity. The major management
      challenges were poor financial status of patients precluding necessary diagnostic
      laboratory and imaging studies. Early recognition, diagnosis and treatment are
      crucial to the preservation of vision and reduced occurrence of complications.
      The importance of record keeping is also highlighted.

PMID- 24568054
TI  - Effects of streptozotocin, fructose and sucrose-induced insulin resistance on
      plasma and urinary electrolytes in male Sprague-Dawley rats.
AB  - BACKGROUND: Several groups in recent times have related the pathogenesis of renal
      haemodynamic changes in diabetes and most of the experimental diabetic conditions
      studied so far were carried out using streptozotocin injection only. OBJECTIVE:
      The aim of the present study was to examine the effects of streptozotocin,
      fructose and sucrose induced insulin resistance on plasma and urinary
      electrolytes. Closely related to this aim, was the view to suggest which
      profoundly potentiate insulin resistance more between fructose and sucrose.
      METHODS: Thirty-six male Sprague-Dawley rats were randomly divided into 6 groups
      Group 1 > control group. Group 2 > served as streptozotocin group, rendered
      diabetic by a single dose IP injection of Streptozotocin 45 mg/kg in 0.1 M
      freshly dissolved in Na+ citrate buffer pH 4.5. Hyperglycaemia confirmed after 48
      hours. Groups 3 and 4 > served as 25% fructose and 50% fructose groups
      respectively; fed on a diet containing 25% and 50% fructose (W/W) for 12 weeks.
      Groups 5 and 6 > served as 25% sucrose and 50% sucrose groups respectively; fed
      on a diet containing 25% and 50% sucrose (W/W) for 12 weeks. Hyperglycaemia
      confirmed at the 12th week. RESULTS: Plasma and urinary sodium and potassium were
      significantly higher (P < 0.05) in the 25% and 50% sucrose groups compared to the
      other groups. Plasma and urinary chloride was significantly higher (P < 0.05) in
      the 25% and 50% fructose groups compared to the other groups. Plasma creatinine
      and urea was significantly higher (P < 0.05) in the streptozotocin, 25% and 50%
      Sucrose groups compared to all the other groups. Urinary creatinine and urea was
      significantly higher (P < 0.05) in the streptozotocin, and 25% Fructose groups
      compared to all the other groups. CONCLUSION: The elevated levels of plasma and
      urinary electrolytes are presumptive markers of diabetes associated lesions in
      the kidneys of rats. Fructose potentiated insulin resistance effect more than
      sucrose though sucrose might have more effect on renal sodium handling.

PMID- 24568056
TI  - The accuracy of ultrasonography in the diagnosis of breast pathology in
      symptomatic women.
AB  - BACKGROUND: Breast cancer is the most frequently diagnosed cancer and the leading
      cause of cancer death among females, accounting for 23% of total cancer cases and
      14% of cancer deaths worldwide. The developing countries are catching up with
      this trend. Breast ultrasound when properly performed and interpreted, is an
      indispensable tool in breast imaging. The early diagnosis and treatment of breast
      masses reduces the morbidity and mortality associated with delayed diagnosis of
      breast carcinoma. The use of breast ultrasound is gaining ground in recent time,
      this is due to current advances in ultrasound technology which permit greater
      spatial and contrast resolution and shortened scan time. OBJECTIVE: To determine
      the sensitivity, specificity and positive predictive value of ultrasound in the
      detection of palpable breast masses and to correlate the findings of ultrasound
      with the findings of fine needle aspiration cytology, or histopathology. METHODS:
      Breast ultrasound scanning was done in 100 patients with signs and symptoms of
      breast lesion referred from the Surgical out Patient Clinic to the Radiodiagnosis
      Department of Lagos University Teaching Hospital (LUTH). Histology reports were
      collected from either the case note or Morbid Anatomy department to correlate the
      findings with ultrasound diagnosis. RESULTS: The mean age was 41.7 +/- 11.34 (18
      59) years. Symptoms of breast lesion were highest in the age group 41-50 years 38
      (38%), and least in 18-20 years 4 (4%). When the use of ultrasonography was
      compared with the histopathology report in the diagnosis of breast lesion in the
      studied population, the sensitivity was 100%, specificity (96.6%), accuracy
      (97%), posting predictive value (PPV) 81.3%, and negative predictive value (NPV)
      100%. The accuracy, specificity and PPV however decreased with increasing age.
      CONCLUSION: Ultrasonography of the breast is useful in the diagnosis of breast
      lesions, because of the high sensitivity, specificity and diagnostic value it
      exhibited with histopathologic findings.

PMID- 24568057
TI  - Neurobehavioural and neurotoxic effects of L-ascorbic acid and L-tryptophan in
      lead exposed rats.
AB  - BACKGROUND: Lead is an environmental toxicant, occupational and environmental
      exposures remain a serious problem in developing and industrializing countries.
      OBJECTIVE: This study is designed to investigate the effects of L-ascorbic acid
      and L-tryptophan on the neurotoxicity and neurobehavioural alterations in lead
      exposed male Sprague Dawley rats. METHODS: Experimental animals were exposed to
      oral doses of lead (Pb), L-ascorbic acid, and L-tryptophan at 75 mg/kg body
      weight, 40 mg/kg body weight, and 20 mg/kg body weight respectively, while
      control animals received 0.90% saline solution. Oral administration spanned for
      four weeks after which changes in neuro-behaviour, organ weight, blood deposition
      of Pb, brain serotonin, tryptophan and neuronal redox status were determined.
      Changes in organ weight, blood lead levels, neuro-behavioural characteristics,
      brain serotonin and tryptophan contents, and brain redox status were determined.
      RESULTS: The results indicated that Pb exposure increased blood lead, organ
      weight index, and behavioural signs of anxiety and aggression. The sub-chronic
      exposure to Pb also decreased brain serotonin, while causing oxidative stress by
      decreasing reduced glutathione levels, antioxidant enzyme activity and increasing
      lipid peroxidation and brain protein contents. L-ascorbic acid attenuated both Pb
      induced neuronal oxidative stress, and abnormalities in behaviour. But L
      tryptophan ameliorated Pb altered neurobehaviour with no significant effect on Pb
      induced oxidative stress in the brain. Co-administration of L-ascorbic acid and L
      tryptophan on Pb exposed rats showed a reversal in all indices assessed towards
      the physiological state of control. CONCLUSION: This suggests that L-ascorbic and
      L-tryptophan can be used to compliment chelating therapy in lead neurotoxicity.

PMID- 24568058
TI  - Pharmacist's intervention in the control of blood sugar levels in randomised
      diabetes patients at a primary health care setting in Benin City.
AB  - BACKGROUND: The extended roles of pharmacists in Nigeria in the improvement of
      quality of health care at the primary health care (PHC) level is currently poorly
      executed even though pharmacists have been proven to be involved in
      interventional activities in health care delivery. OBJECTIVE: To evaluate
      pharmacists' intervention in the control of blood sugar levels of diabetes
      patients in a PHC setting in Benin City, Nigeria. METHODS: At baseline, the
      fasting blood sugar (FBS), glycosylated hemoglobin (HbA1c), body mass index (BMI)
      and blood pressure (BP) of randomly selected 170 diabetic patients in a primary
      health care centre were evaluated. This was followed-up with intervention by the
      pharmacists through counselling on lifestyle modification, self-medication and
      drug adherence on monthly basis for three consecutive months after which the FBS,
      HbA1c, BMI and BP were re-evaluated. RESULTS: indicated significant reduction in
      BMI, HbA1c and FBS from 27.1 +/- 4.2 kg/m2, 8.1 +/- 3.0% and 10.0 +/- 4.2 mmol/l
      to 23.5 +/- 3.5 kg/m2, 7.1 +/- 1.8% and 8.5 +/- 2.1 mmol/l, respectively (p <
      0.001) was observed following the intervention by the pharmacists. CONCLUSION:
      Direct involvement of pharmacists in the care of diabetic patients in PHC
      settings can significantly improve the quality of life provided to these patients
      and hence reduce mortality resulting from the disease. Recruitment of reasonable
      number of pharmacists should always be considered in health policies for PHC
      settings in developing countries.

PMID- 24568060
TI  - Causes and pattern of tooth loss in children and adolescents in a Nigerian
      tertiary hospital.
AB  - BACKGROUND: Tooth loss diminishes the quality of life and is also related to
      poorer general health. Premature tooth loss in children can have devastating
      effects such as compromised aesthetics and function, mesial and distal drifts of
      adjacent teeth leading to crowding and impaction of the permanent successors and
      other forms of malocclusion. OBJECTIVE: To assess the causes and pattern of tooth
      loss in children and adolescents at the Paedodontic Clinic of the Lagos
      University Teaching Hospital, Lagos. METHODS: This retrospective study was
      carried out at the Paedodontic Unit of the Lagos University Teaching Hospital,
      Lagos using clinical records over a period of time from January 2008 to April
      2010. Information obtained included age, gender, missing and extracted teeth, and
      reasons for extraction/tooth loss. Exfoliated primary teeth and congenitally
      missing teeth were excluded. Data was analysed using Epi info 2007 statistical
      software. Chi-square test was used to compare proportions of tooth loss among age
      groups. The level of significance was set at P < 0.05. RESULTS: A total of 493
      patients aged 1-16 years had lost one or more teeth due to various reasons. There
      were 244 (49.5%) males and 249 (50.5%) females. Majority of the subjects lost
      their teeth due to caries and its sequelae (64.3%) compared to trauma (10.8%) and
      orthodontic reasons (23.5%). Seven (1.4%) lost their teeth due to failure of
      previous treatment such as pulp therapy. CONCLUSION: Extraction largely due to
      caries and its sequelae was responsible for most of the tooth loss among the
      study population. There is the need for intensified oral health education and
      awareness programmes in the populace with emphasis on prevention of dental caries
      and early presentation for dental treatment in order to avert premature tooth
      loss in children and adolescents.

PMID- 24568059
TI  - The Nigerian Postgraduate Medical Journal 1999 to 2008: a scientometric
      appraisal.
AB  - BACKGROUND: Scientometric is one of the emerging concepts used to analyze the
      growth, structure, interrelationships amongst the disciplines and the
      productivity of the volume of intellectual publications. For the sake of
      qualitative acquisition of the relevant information resources from the avalanche
      of the information world, scientometric or bibliometric is relevant research
      methodological approach that will enhance quality collection and determines the
      core texts, core journals, core information and core research areas. Hence its
      absence of application may negate medical libraries collection development.
      OBJECTIVE: The essence of the research work is to determine the quantum volume of
      research output, patterns of research collaboration by authorship, geographical,
      subject, and citations distributions. METHODS: Information was transcribed on
      cataloguing cards for the generation of databank. Subject analysis was done by
      using medical subject headings 2010 edition and Bradford's Statistical
      methodology was used to analyze the data. RESULTS: Results showed that a total
      number of articles produced was 576. The most productive research year was 2007
      which pooled 80 (13.9%) articles and 12,182 was the total number of references
      cited.Also, year 2007 pooled the highest number of references cited 1722 (14.1%).
      December issues ranked the highest with 151 articles, September issues produced
      the highest citations with 3,409; two authorship collaborations accounted for the
      highest number with 162 (28.1%) articles. CONCLUSION: Adoption of scientometric
      or bibliometric or informetric in analyzing journal for a period of time is a
      useful strategy to know the direction of publication of a journal, its strengths
      and weaknesses, unravels high concentration areas and the low concentration areas
      and helps to harmonize the deficiencies.

PMID- 24568061
TI  - Preparedness of government owned dental clinics for the management of medical
      emergencies: a survey of government dental clinics in Lagos.
AB  - BACKGROUND: An emergency is a medical condition demanding immediate treatments.
      OBJECTIVE: The aim of the study was to determine the knowledge and ability of
      dental surgeons in the management of medical emergencies and the availability of
      emergency drugs and equipment in government dental clinics and hospitals in Lagos
      State. METHODS: The study was a descriptive cross-sectional study of knowledge
      and ability of Dental Surgeons in the management of medical emergencies,
      prevalence of medical emergencies in dental practice and availability of
      emergency drugs and equipment in dental practice in government dental clinics and
      hospitals in Lagos State. The study covered 22 government dental clinics and
      hospitals in Lagos State. Data obtained was entered into a computerand analyzed
      using Statistical Package for Social Science (SPSS) Version-16 data analysis
      software. Chi Square and cross-tabulations were used for the analysis. A 95%
      Confidence Level was used and a p-value of less than or equal to 0.05 was
      considered statistically significant. RESULTS: Of a population of 255 Dental
      Surgeons on the nominal rolls of all the health institutions, 224
      (87%)responded.Of the total respondents, 204 (91.1%) stated they had no emergency
      kit in their dental clinics (p < 0.05) while 158 respondents (70.5%) stated they
      had no emergency drugs in their dental practice to manage medical emergencies (p
      < 0.05). The commonest emergencies reported was syncope 104 respondents (33.8%).
      161 respondents (71.9%) claimed they are able to manage medical emergencies
      encountered in their dental practice if kits and drugs are available. CONCLUSION:
      The findings of the study show that government dental clinics/hospital in Lagos
      seem not to be adequately prepared to manage medical emergency. Although 71.9% of
      the dentist claimed they could mange such emergencies should they arise 91.1% and
      70% of the respondent claimed they and no emergency kits and drugs to manage such
      emergencies in their hospital respectively should they arise.

PMID- 24568062
TI  - Honey improves healing of circumscribed excision injury to the paniculus adiposus
      in albino rats.
AB  - BACKGROUND: Honey promoteswound healing. OBJECTIVE: In this study, we described
      the anatomical perspective of honey on wound healing in male rats. METHODS: The
      twenty-four male rats used were randomly divided equally into treated
      Experimental (E) and Control (C) groups. Infliction of wound done under
      anaesthesia; honey was used for wound dressing in E, distilled water firmly held
      by plaster in C. Monitoring of wound contraction were carried out at the interval
      of three days till the wound healed. The histology of granulation tissue excised
      from the wounds of rats was also done. RESULTS: Mean wound contraction (%) of
      rats in E on days 3, 6, and 9 were: 35.32 +/- 5.5; 57.56 +/- 0.7 and 82.30 +/-
      0.9% compared to 26.50 +/- 1.2; 46.69 +/- 0.4 and 61.24 +/- 1.0% of rats in C.
      Honey treated groups showed significant increase (p < 0.05) in percentage of
      wound contraction in all treatment days. Complete wound closure day was also
      significantly shorter. On day 3, E showed a more intense infiltration by
      neutrophils and macrophages as well as features suggestive of edema and necrosis.
      On day 9, the connective tissues of E revealed markedly increased fibroblasts,
      less neutrophils, and presence of numerous new capillary blood vessels.
      CONCLUSION: The use of honey accelerates the wound healing process.

PMID- 24568063
TI  - Minimising cornea scarring from the use of harmful traditional eye remedies in
      developing countries.
AB  - Corneal scarring is the fourth largest cause of blindness globally, and a much
      more prominent factor in developing countries. Blindness from corneal scarring is
      largely a preventable phenomenon, and is capable of causing significant morbidity
      that can last for a lifetime. A significant proportion of these cases are caused
      by the use of harmful traditional eye medicines/remedies, and are used and
      prescribed by friends, relatives and traditional healers, with widespread use
      especially in developing countries. Use of traditional remedies can also cause
      harm indirectly by causing delays before seeking medical treatment. Reducing
      corneal scarring from the use of harmful traditional medicine is through a
      combination of approaches with the key strategies being community diagnosis,
      education, participation, and intervention, with provision of basic eye care
      integrated into the primary health care of the community. Collaboration with
      traditional healers in the community is also another approach that has been found
      to be useful.

PMID- 24568064
TI  - Pipkin fractures: fracture of the head of femur a case report.
AB  - Pipkin fracture is the fracture of the head of the femur. It can be associated
      with neck of femur fracture or/and posterior dislocation of the hip. This
      fracture is very rare fracture and has not been reported at our sub-region. We
      present this fracture in a 26 year old with a type I Pipkin fracture treated with
      closed reduction and percutaneous k-wire fixation. Five (5) year after, she was
      very appreciative of her management with satisfactory remodeling of her femoral
      head.

PMID- 24568065
TI  - Willingness of Nigerians to donate a kidney.
AB  - BACKGROUND: Kidney transplantation is a popular modality of RRT in the developed
      world. OBJECTIVE: To assess the willingness of the general population of
      Nigerians across the country to donate a kidney METHODS: This is a multiregional,
      cross sectional, questionnaire based study. One thousand Three hundred
      respondents participated in the study. This study was carried out in four major
      Towns and cities across Nigeria between January 2009 and December 2010. The
      locations are Birnin Kebbi in the north, Ilorin in the middle belt, Iddo Ekiti in
      the south and Lagos, the economic capital of Nigeria. The respondents were
      randomly selected within the four localities. Those below the age of 16 or above
      the age of 65 years were excluded from the study RESULTS: There were 727 (55.9%)
      males. The mean age (S.D) of respondents was 39.5 (10.7) years. The largest
      population of participants, 494 (38.3%) were non health workers and 692 (53.2%)
      of them were Muslims. Eight hundred and fifty eight (66%) of the participants
      were willing to donate a kidney. Twenty five percent (25% were not willing and
      115 (8.9%) were not sure. Majority of those who were unwilling to donate a
      kidney, 325 (99.4%) will not change their minds even if they were to be given
      incentives CONCLUSION: Nigerians are willing to donate a kidney irrespective of
      geographical location, religion or gender and many are willing to do so
      altruistically.

PMID- 24568067
TI  - Repair of defective composite resin restoration: current trend among conservative
      dentists in Nigeria.
AB  - BACKGROUND: Repair of defective composite resins restorations is being
      increasingly recognized as a viable alternative to replacement. there is however
      no consensus yet on the treatment protocol. OBJECTIVE: To determine the views and
      practice of specialists in Conservative Dentistry in Nigeria as regard to repair
      procedure of defective composite resin restorations. METHODS: A cross sectional
      study was conducted among conservative dentists in Nigeria using anonymous
      structured and open-ended questionnaire as instrument for data collection, the
      data collected were: socio demographic variables; views and practice of the
      respondents as regards the indications, benefits and longevity of composite
      resins repair treatment option and type of surface preparation usually employed,
      summary statistics was performed. RESULTS: The respondents comprise 9 (37.5%)
      males and 15 (62.5%) females. Marginal defect (91.7%) was the strongest
      indication and preservation of tooth structure (95.8%) was regarded as the
      topmost benefit, majority of the respondents (75.0%) considered repair procedure
      as a definitive treatment and etching with phosphoric acid was the most utilized
      surface preparation (87.5%). CONCLUSION: The views and practice of the
      respondents is in the literature.

PMID- 24568066
TI  - C-reactive protein in healthy adult Nigerians.
AB  - BACKGROUND: C-reactive protein (CRP) is an acute phase reactant produced in the
      liver in response to tissue injury or systemic inflammation, its release is
      stimulated by cytokines (interleukin-6 and tumour necrosis factor-alpha).
      Elevated CRP levels have been linked to an increased risk of later development of
      diabetes mellitus and systemic hypertension. Baseline level of C-reactive protein
      in apparently healthy men and women predict long-term risk of a first myocardial
      infarction. METHOD: The study design was cross-sectional conducted among
      apparently healthy adult relative of patients and hospital staff of the Obafemi
      Awolowo University Teaching Hospitals complex (OAUTHC) Ile Ife, Osun State south
      western Nigeria. Serum lipids and fasting blood glucose were measured, while C
      reactive protein measurement was based on the principle of solid phase enzyme
      linked immunosorbent assay (ELISA). RESULTS: Atotal of 50 apparently healthy
      consecutive adult subjects were recruited into the study comprising 19 male and
      31 female. There was no significant difference in mean Fasting blood glucose and
      serum lipids between the male and female study subjects. However, C-reactive
      protein was found to be higher in female compared to male, but the difference was
      not statistically significant. CONCLUSION: This study showed that apparently
      healthy adult female Nigerians have higher level of C-reactive protein compared
      to male, but with no significant difference.

PMID- 24568068
TI  - The Food Frequency Questionnaire abandonment debate: time to resolve.

PMID- 24568069
TI  - Development and validation of a Food Frequency Questionnaire (FFQ) for assessing
      sugar consumption among adults in Klang Valley, Malaysia.
AB  - INTRODUCTION: The aim of this study was to develop and validate a
      semiquantitative food frequency questionnaire (FFQ) for assessing habitual added
      sugar consumption of adults in the Klang Valley. METHODS: In the development
      phase, a 24-hour dietary recall (24-hr DR) was used to determine food items to be
      included into the FFQ among adults from three major ethnicities (n = 51). In the
      validation phase, the FFQ was further validated against a reference method which
      was a multiple-pass 24-hr DR among 125 adults in Klang Valley. The response rate
      for the latter phase was 96.1%. RESULTS: The semi-quantitative FFQ consisting of
      64 food items was categorised into 10 food groups. The mean added sugar intake
      determined by the reference method was 44.2 +/- 20.2 g/day while that from the
      FFQ was 49.4 +/- 21.4 g/day. The difference in mean intake between the two
      methods was 5.2 g (95% CI = 2.6-7.9; SD = 14.9, p < 0.05) or 11.8%. Pearson
      correlation was r = 0.74 (p < 0.001) for the two methods while Spearman rank
      correlations for the various food groups ranged between 0.11 (cake and related
      foods) to 0.61 (self-prepared drinks), with most groups correlating significantly
      (p < 0.05). Cross-classification of subjects into quintiles of intake showed
      47.2% of the subjects correctly classifying into the same quintile, 34.4% into
      adjacent quintiles while none were grossly misclassified. The Bland-Altman plot
      was concentrated in the y-axis range (-24.14 g to 34.8 g) with a mean of 5.22 g.
      CONCLUSION: This semi-quantitative FFQ provides a validated tool for estimating
      habitual intake of added sugar in the adult population of the Klang Valley.

PMID- 24568070
TI  - Validity and reliability of the Multidimensional Body Image Scale in Malaysian
      university students.
AB  - INTRODUCTION: This study aimed to evaluate the validity and reliability of the
      Multidimensional Body Image Scale (MBIS), a seven-factor, 62-item scale developed
      for Malaysian female adolescents. This scale was evaluated among male and female
      Malaysian university students. METHODS: A total of 671 university students (52.2%
      women and 47.8% men) completed a self-administered questionnaire on MBIS, Eating
      Attitude Test-26, and Rosenberg Self-Esteem Scale. Their height and weight were
      measured. RESULTS: Results in confirmatory factor analysis showed that the 62
      item MBIS reported poor fit to the data, xhi2/df = 4.126, p < 0.001, CFI = 0.808,
      SRMR = 0.070, RMSEA = 0.068 (90% CI = 0.067, 0.070). After re-specification of
      the model, the model fit was improved with 46 items remaining, chi2/df = 3.346, p
      < 0.001, CFI = 0.903, SRMR = 0.053, RMSEA = 0.059 (90% CI = 0.057, 0.061), and
      the model showed good fit to the data for men and women separately. This 46-item
      MBIS had good internal consistency in both men (Cronbach's alpha = 0.88) and
      women (Cronbach's alpha = 0.92). In terms of construct validity, it showed
      positive correlations with disordered eating and body weight status, but negative
      correlation with self-esteem. Also, this scale discriminated well between
      participants with and without disordered eating. CONCLUSION: The MBIS-46
      demonstrated good reliability and validity for the evaluation of body image among
      university students. Further studies need to be conducted to confirm the
      validation results of the 46-item MBIS.

PMID- 24568071
TI  - Association and interaction effect between VEGF receptor-2 (VEGFR-2) gene
      polymorphisms and dietary pattern on blood uric acid in Malays and Indians.
AB  - INTRODUCTION: Gout and hyperuricaemia attributed to genetic and lifestyle factors
      have been associated with several chronic diseases. This study aimed to determine
      the association and interaction effects between vascular endothelial growth
      factor receptor-2 (VEGFR-2) gene polymorphisms (rs1870377 and rs2071559) and
      dietary patterns on blood uric acid in Malay and Indian adults. METHODS: Dietary
      intakes of 153 Malays and 177 Indians were obtained using a food frequency
      questionnaire for the construction of dietary patterns using factor analysis.
      Genotyping of rs1870377 and rs2071559 was performed by real-time PCR using TaqMan
      probes. Anthropometric measurements, body mass index (BMI) and blood pressure and
      biomarkers, uric acid, glycated haemoglobin A1c (HbA1c), and blood lipids were
      determined. RESULTS: There were significant differences in the mean values for
      HbA1c (41 +/- 12 vs 45 +/- 8 mmol/mol, p < 0.001) and blood lipids levels (p <
      0.05) between Malays and Indians. Significant correlations were obtained between
      uric acid with selected blood lipids (p < 0.05) and BMI in Malays (r = 0.362, p <
      0.001) and Indians (r = 0.212, p < 0.01). Four dietary patterns were extracted
      from dietary intakes of all subjects: 'Vegetables diet'; 'Fruits diet' (FD);
      'Animal protein and rice diet'; and 'Fast foods and preserved foods diet'. There
      were no significant associations between dietary patterns (p = 0.054-0.609) and
      VEGFR-2 gene polymorphisms (p = 0.348-0.778) with uric acid. In Malay subjects,
      the interaction of rs2071559 and FD had a borderline effect (p = 0.05) on blood
      uric acid after adjusting for potential confounders. CONCLUSION: The associations
      and gene-diet interactions involving VEGFR-2 gene polymorphisms and FD on uric
      acid provide new information on gout and hyperuricaemia risks in Malays.

PMID- 24568072
TI  - Comparison of body adiposity indices in predicting blood pressure and
      hypertension among slum-dwelling men in Kolkata, India.
AB  - INTRODUCTION: Recent findings show a high incidence of stroke among slum dwellers
      in Kolkata, India. This cross-sectional study aimed to compare the association of
      different adiposity indices to blood pressure (BP) and hypertension (HT) among
      slum-dwelling Bengalee men in Kolkata. METHODS: Measurements of height, weight,
      waist and hip-circumferences, biceps, triceps, subscapular and suprailiac
      skinfolds, systolic (SBP) and diastolic (DBP) of 470 men aged 18-60 years were
      taken. Body mass index (BMI), body adiposity index (BAI), percent body fat, waist
      height (WHtR) and waist-hip ratios (WHR) were computed. The effect of adiposity
      values on HT was estimated by logistic regressions, while partial correlations
      and linear regressions analyses of SBP and DBP with each index were performed.
      RESULTS: BMI had the strongest correlation with blood pressure. The newly
      proposed index, BAI, had significant but considerably lower correlations with
      both BP compared to BMI and central adiposity. Both BMI and WHtR explained DBP
      with equal efficacy. Abdominal obesity, measured by WC, showed the strongest
      association with risk of HT, independent of age and BMI. The predictive effect of
      abdominal adiposity on blood pressure (SBP and DBP) appeared to be modified by
      age-BMI interaction. CONCLUSION: BAI showed no advantage over other adiposity
      measures in the prediction of hypertension among the men in this study. Waist
      circumference was the best obesity measure to predict hypertension and may be
      preferred to BMI considering its simplicity of measurement. The simple measure of
      WC might help in easy screening of hypertension among the poor people in resource
      constrained settings such as those in urban slums.

PMID- 24568073
TI  - Effect of n-3 supplementation on hyperactivity, oxidative stress and inflammatory
      mediators in children with attention-deficit-hyperactivity disorder.
AB  - BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is associated with
      difficulties in learning, behaviour and psychosocial adjustment that persist into
      adulthood. Decreased omega-3 fatty acids and increased inflammation or oxidative
      stress may contribute to neuro-developmental and psychiatric disorders such as
      ADHD. The aim of this study was to determine the effect of n-3 supplementation on
      hyperactivity, oxidative stress and inflammatory mediators in children with ADHD.
      METHODS: In this double blind study, 103 children (6-12 years) with ADHD
      receiving maintenance therapy were assigned randomly into two groups. The n-3
      group received n-3 fatty acids (635 mg eicosapentaenoic acid (EPA), 195 mg
      docosahexaenoic acid (DHA)), and the placebo group received olive oil capsules
      which were visually similar to the n-3 capsules. The duration of supplementation
      was 8 weeks. Plasma C-reactive protein (CRP), interleukin-6 (IL-6) and the
      activity of glutathione reductase (GR), catalase (CAT) and superoxide dismutase
      (SOD) were determined before and after the intervention. Likewise the Conners'
      Abbreviated Questionnaires (ASQ-P) was applied. RESULTS: After 8-week
      intervention, a significant reduction was observed in the levels of CRP ( P <
      0.05, 95% CI = 0.72-2.02) and IL-6 (P < 0.001, 95% CI = 1.93-24.33) in the n-3
      group. There was also a significant increase in activity of SOD and GR (P <
      0.001). A significant improvement was seen in the ASQ-P scores in the n-3 group
      (P < 005). CONCLUSION: Eight weeks of EPA and DHA supplementation decreased
      plasma inflammatory mediators and oxidative stress in the children with ADHD.
      These results suggest that n-3 fatty acid supplementation may offer a safe and
      efficacious treatment for children with ADHD.

PMID- 24568074
TI  - Comparison of changes in postprandial serum leptin between healthy and type 2
      diabetic individuals.
AB  - INTRODUCTION: Leptin resistance may be intensified by insulin resistance. This
      vicious cycle between insulin resistance and leptin resistance may increase
      feelings of hunger and reduce energy expenditure and ultimately increase obesity.
      In this study, postprandial changes in leptin, insulin and glucose were compared
      between healthy subjects and patients with Type 2 diabetes mellitus (DM).
      METHODS: Six men with Type 2 DM and seven healthy men (matched for age and body
      mass index), after 12 hours of fasting, ate the same Iranian meal (chelo kebab
      kobibeh) consisting of 46% carbohydrate, 21% protein, 33% fat and 743 kcal
      energy. Blood samples were obtained before and 1, 2 and 4 hours after the meal,
      and serum leptin, insulin and glucose levels were measured. The area under
      incremental curve (AUIC) computed using the Trapezoidal method with fasting
      values was deducted from each time point, yielding net postprandial changes.
      RESULTS: Leptin levels at the first hour were significantly reduced in both
      groups and then increased at the second and fourth hours after the meal, although
      not reaching fasting values in the diabetic group at the 4th hour. AUIC for
      leptin was significantly lower in the diabetic group (p = 0.023). Despite high
      levels before the meal, the early increase in insulin in the diabetic group was
      lower and declined more slowly than in the healthy group. The incremental area
      under the insulin curve was significantly lower in the control group than in the
      diabetic group (p = 0.006). CONCLUSION: It appears that an increased leptin level
      two hours after the meal is due to increased serum insulin and glucose levels.
      Leptin AUIC after meals in people with Type 2 DM is lower than in healthy people
      and may be due to decreased responsiveness to insulin in adipocytes because of
      insulin resistance.

PMID- 24568075
TI  - Plasma total antioxidant capacity (TAC) in obese Malaysian subjects.
AB  - INTRODUCTION: There is a pressing need to better understand the complex
      biochemical pathways that lead to the pathogenesis of obesity. Increased
      oxidative stress and decreased antioxidant capacity have been identified to be
      associated with obesity. Therefore, the objectives of this study were to
      determine the plasma total antioxidant capacity (TAC) levels of Malaysian
      subjects and to evaluate its potential association with obesity and related
      anthropometric measurements. METHODS: Plasma TAC of 362 multi-ethnic Malaysian
      subjects from the Kampar Health Clinic (138 males, 224 females; 124 ethnic
      Malays, 152 Chinese, 86 Indians; 192 non-obese, 170 obese) was measured using
      Trolox equivalent antioxidant capacity (TEAC) 96-well plate assay. RESULTS:
      Plasma TAC was significantly lower in obese subjects (M +/- SE = 292 +/- 10.4
      micromol/L) compared to non-obese subjects (397 +/- 8.58 micromol/L), whereas it
      was significantly higher in males and those in the 21-30 age group. Those with
      salty food preference and practising a strict vegetarian diet also had
      significantly higher plasma TAC. However, no association was found for other
      dietary habits (coffee intake) and lifestyle factors (physical activity,
      smoking). Plasma TAC was also significantly negatively correlated with diastolic
      blood pressure, waist and hip circumferences, weight, body mass index, total body
      fat, % subcutaneous fat, visceral fat level, resting metabolism and % skeletal
      muscle. CONCLUSION: Plasma TAC was found to be associated with obesity, strict
      vegetarian practice, salty food preference and all obesity anthropometric
      indicators, except systolic blood pressure and pulse rate. Obese people have
      decreased plasma TAC indicating a compromised systemic antioxidant defence and
      increased oxidative stress.

PMID- 24568076
TI  - Hydrophilic antioxidant capacities and total phenol content of seasonal fruits of
      Bangladesh.
AB  - INTRODUCTION: Consumption of fruits and vegetables helps to scavenge free
      radicals owing to the presence of antioxidant nutrients and secondary
      metabolites, especially polyphenolic compounds. This may lead to a reduction in
      the risk of diet-related chronic diseases. The purpose of the study was to
      determine the antioxidant capacity (AC) and total phenolic content (TPC) of
      selected seasonal fruits of Bangladesh. METHODS: Hydrophilic extracts from edible
      portions of fifteen fruits available in the summer season were analysed. Total
      phenol content was determined spectrophotometrically according to the Folin
      Ciocalteau method while antioxidant capacity was determined by 2, 2-diphenyl-1-1
      picrylhydrazyl radical scavenging activity (DPPH-RSA). RESULTS: TPC ranged from
      0.6 +/- 0.01 to 0.01 +/- 0 mg Gallic acid equivalent (GAE)/g of fresh weight
      (FW). Antioxidant capacity varied from 4.882 +/- 0 to 0.113 +/- 0.03 micromol
      Torolox equivalents (TE)/g of FW. Carissa carandas showed the highest AC (4.882
      +/- 0 micromol TE/g), while the lowest (0.113 +/- 0.3 micromol TE/g) was seen in
      Baccaura ramiflora. A positive and significant correlation (R2 = 0.957) between
      antioxidant capacity and total phenolic content of the analysed samples was
      identified. A significant and positive correlation (p < 0.05) between AC and TPC
      was found in Manikara zapota, Artocarpus heterophyllus, Litchi chinensis and
      Articarpus lakoocha. CONCLUSION: The data indicates that some indigenous seasonal
      fruits of Bangladesh contain high polyphenols that may serve as a potential
      source of dietary antioxidants.

PMID- 24568077
TI  - Nutritional content and in vitro antioxidant potential of Garcinia atroviridis
      (Asam gelugor) leaves and fruits.
AB  - INTRODUCTION: The objective of this study was to determine antioxidant potential
      of Garcinia atroviridis leaves and fruits extracts in vitro. METHODS: Antioxidant
      activity was assessed using 1,1-diphenyl-2-picrylhydrazyl (DPPH) and ferric
      reducing antioxidant power (FRAP) assays. Total phenolic content (TPC) of the
      extracts was estimated as gallic acid equivalent by Folin-Ciocalteau method.
      Proximate analysis was determined based on the Association of Official Analytical
      Chemists (AOAC) procedures. RESULTS: Garcinia atroviridis leaves extracted at 100
      degrees C/15 min demonstrated the highest TPC value (21.21 +/- 0.28 mg GAE/mg)
      and was significantly different (p < 0.05) from that of leaves extracted at 60
      degrees C/6 h and 40 degrees C/12 h. On the other hand, the fruit extracted at 60
      degrees C/6 h showed the highest TPC value (16.23 +/- 0.18 mg GAE/mg) (p < 0.05)
      compared to the fruit extracted at 40 degrees C/12 h and 100 degrees C/15 h
      respectively. The antioxidant activities of both samples were positively
      correlated with the TPC values based on DPPH-radical-scavenging activity and
      ferric reducing power estimation. Garcinia atroviridis leaf extract contained
      significantly higher proteins, carbohydrate and ash contents (2.16% +/- 0.08;
      15.98% +/- 0.12 and 0.72% +/- 0.07 respectively) than its fruit extract (0.46% +/
      0.08, 8.64% +/- 0.06 and 0.15% +/- 0.06) respectively). The energy content was
      also found to be higher in the leaf (73.64% +/- 2.15) compared to the fruit
      (38.38% +/- 1.72) (p < 0.05). CONCLUSION: The findings indicate that G.
      atroviridis leaves and fruits have potential for use as a source of natural
      antioxidants and nutrients for therapeutic purposes against free radical mediated
      health conditions.

PMID- 24568078
TI  - Comparison of nutritional qualities and antioxidant properties of ready-to-eat
      fruit-enriched corn based breakfast cereals.
AB  - INTRODUCTION: The study aimed to analyse the nutritional quality, antioxidant
      components and activity of three varieties of corn based ready-to- eat (RTE)
      breakfast cereals (BFC) enriched with strawberry, banana and mango. METHODS:
      Fruit-enriched corn based breakfast cereals manufactured in India were purchased
      and ground to obtain homogeneous samples for analysis. The contents of moisture,
      protein, total fat, dietary fibre, iron, phosphorous, calcium, vitamin C, total
      carotene, thiamine, riboflavin, in vitro digestible protein, bioaccessible
      calcium and iron, and digestible starch fractions were determined. The
      antioxidant components namely, polyphenols, flavonoids and antioxidant activity
      in different extracts were also determined using total antioxidant, free radical
      scavenging (2,2-diphenyl-1-picrylhydrazyl) and reducing power assays. RESULTS:
      The protein and dietary fibre contents in all samples ranged between 4.0-4.6 and
      6.4-7.6 g/ 100g respectively. Total iron and vitamin C ranged between 10.7-13.3
      mg and 33.2-43.6 mg/100g respectively. Cereals with mango had high total carotene
      in comparison with other samples. In vitro digestible protein of the processed
      cereals was low, while bioaccessible calcium (50.2-59.5%) and iron (8.5-15.1%)
      levels were high due to low oxalates and phytic acid contents. The starch
      profiles of the breakfast cereals showed high rapidly available glucose and
      starch digestibility index. Fruit-enriched breakfast cereals showed high
      polyphenol content in methanol extract (48.6-71.3 mg/100g) and high total
      antioxidant activity in aqueous extracts. Free radical scavenging and reducing
      power assay showed high activity in 80% methanol extract. CONCLUSION: Fruit
      enriched breakfast cereals have the potential to be a good source of iron,
      dietary fibre, vitamin C and total carotene. The fruit-enriched cereals also had
      high bioaccessible iron and antioxidant activity.

PMID- 24568079
TI  - Folate content and availability in Malaysian cooked foods.
AB  - INTRODUCTION: Data on folate availability of Malaysian cooked foods would be
      useful for estimation of dietary folate intake; however such information is
      scarce. METHODS: A total of 53 samples of frequently consumed foods in Malaysia
      were selected from the Nutrient Composition of Malaysian Foods. Folate content
      was determined using HPLC method hyphenated with a stainless steel C18 column and
      ultraviolet detector (lambda = 280 nm). The index of folate availability was
      defined as the proportion of folate identified as monoglutamyl derivatives from
      the total folate content. RESULTS: Total folate content of different food samples
      varied from 30-95 microg/100g fresh weight. Among rice-based dishes, the highest
      and the lowest total folate was in coconut milk rice (nasi lemak) and ghee rice
      (nasi minyak), respectively. In noodle dishes, fried rice noodle (kuey teow
      goreng) and curry noodle (mee kari) had the highest folate contents. The highest
      index of folate availability was in a flat rice noodle dish (kuey teow bandung)
      (12.13%), while the lowest was in a festival cake (kuih bakul) (0.13%). Folate
      content was found to be negatively related to its availability. CONCLUSION: This
      study determined folate content and folate availability in commonly consumed
      cooked foods in Malaysia. The uptake of folate from foods with high folate
      content may not be necessarily high as folate absorption also depends on the
      capacity of intestinal deconjugation and the presence of high fibre in the foods.

PMID- 24568080
TI  - Use of red palm oil in local snacks can increase intake of provitamin A
      carotenoids in young aborigines children: a Malaysian experience.
AB  - INTRODUCTION: Carotenoid-rich red palm oil (RPO)-based snacks have been provided
      to children in impoverished communities to improve their vitamin A status. The
      non-availabilty of information on the acceptability of RPO-based snacks by
      Malaysian aborigines (Orang Asli) children forms the basis of this study.
      METHODS: Twenty-one Orang Asli children, majority of whom had normal body mass
      index for age (BMI-for-age) and aged 4.73 +/- 0.92 years in Sungai Tekir, Negeri
      Sembilan were provided with three freshly-prepared snacks (springroll, curry puff
      or doughnut) each containing one teaspoon or 5 ml of RPO per serving, on separate
      mornings. On the fourth morning, one serving each of all 3 different snacks was
      provided together on a plate to every child for consumption and preference for
      the snacks recorded. The children's habitual vitamin A intakes were assessed by a
      semi-quantitative food frequency questionnaire (FFQ) and carotenoid retention
      tests for the prepared snacks were performed by column chromatography. RESULTS:
      Fifty-four percent of the children did not meet their RNI for vitamin A. Based on
      acceptance criterion of consuming at least one-half serving of the snacks
      provided, springroll and curry puff recorded 100% acceptability while doughnut
      had 82% acceptability. Preference of snack was in the order, springroll (47%) >
      doughtnut (35%) > curry puff (18%), but a Z-test test for proportions showed no
      statistical significance. Carotenoid retention tests showed great variation
      between snacks namely, doughnut (100%) > springroll (84%) > curry puff (45%).
      CONCLUSION: The overall findings indicate that the RPO-based snacks are highly
      acceptable and can be used to improve the dietary intake of provitamin A
      carotenoids of Malaysian Orang Asli children.

PMID- 24568081
TI  - Toward civility. ANA, nurses promote strategies to prevent disruptive behaviors.

PMID- 24568082
TI  - The war on superbugs. Addressing the issue of antibiotic resistance.

PMID- 24568084
TI  - On less familiar ground: strategies aim to reduce random floating, improve the
      experience.

PMID- 24568083
TI  - New ICD-10 coding: documentation to provide better care, support more accurate
      billing.

PMID- 24568085
TI  - Calling all nurses: state legislation needed to implement the APRN Consensus
      Model.

PMID- 24568086
TI  - Flu hits young and middle-age adults.

PMID- 24568088
TI  - Feeling like herself again: Idaho nurse credits ANA HealthyNurse pledge as
      motivating change.

PMID- 24568087
TI  - Health, wellness and work environment: how do yours compare?

PMID- 24568089
TI  - Healthy work environments: essential for innovation, transformation.

PMID- 24568091
TI  - Motivated to step up and be more involved.

PMID- 24568090
TI  - Creating a practice environment that supports multigenerational workforce
      collaboration.

PMID- 24568092
TI  - Transcriptional and physiological responses induced by binary mixtures of
      drospirenone and progesterone in zebrafish (Danio rerio).
AB  - Drospirenone (DRS) is a synthetic progestin increasingly used in oral
      contraceptives with similar effects to progesterone (P4). Wild fish are exposed
      to DRS and P4 through wastewater. However, the effects of DRS on fish, both as an
      individual compound and in mixtures, have not been extensively studied.
      Therefore, in this study, global gene expression profiles of ovary and brain of
      female zebrafish (Danio rerio) were characterized after exposure to 55, 553, and
      5442 ng/L DRS for 14 days. The effects were then compared to the observed
      responses after exposure to mixtures of DRS and P4 (DRS+P4: 27 + 0.8, 277 + 8 and
      3118 + 123 ng/L). Transcriptomics findings were related to the changes in
      vitellogenin protein concentrations in the blood, morphology, and histology of
      gonads. Multivariate analysis indicated tissue-, dose-, and treatment-dependent
      expression profiles. Genes involved in steroid hormone receptor activity and
      circadian rhythm were enriched in DRS and mixture groups, among other pathways.
      In mixtures, the magnitude of response was dose- and transcript-dependent, both
      at the molecular and physiological levels. Effects of DRS and P4 were additive
      for most of the investigated parameters and occurred at environmentally relevant
      concentrations. They may translate to adverse reproductive effects in fish. 

PMID- 24568094
TI  - All-nanoparticle layer-by-layer surface modification of micro- and
      ultrafiltration membranes.
AB  - Layer-by-layer (LbL) deposition using primarily inorganic silica nanoparticles is
      employed for surface modification of polymeric micro- and ultrafiltration (MF/UF)
      membranes to produce novel thin film composite (TFC) membranes intended for
      nanofiltration (NF) and reverse osmosis (RO) applications. A wide variety of
      porous substrate membranes with different surface characteristics are
      successfully employed. This report gives detailed results for polycarbonate track
      etched (PCTE), polyethersulfone (PES), and sulfonated PES (SPEES) MF/UF
      substrates. Both spherical (cationic/anionic) and eccentric elongated (anionic)
      silica nanoparticles are deposited using conditions similar to those in prior
      works for solid substrates (e.g., Lee et al.). Appropriate selection of the pH
      for anionic and cationic particle deposition enables construction of nanoparticle
      only layers 100-1200 nm in thickness atop the original porous membrane
      substrates. The surface layer thickness appears to vary linearly with the number
      of bilayers deposited, i.e., with the number of anionic/cationic deposition
      cycles. The deposition process is optimized to eliminate drying-induced cracking
      and improve mechanical durability via thickness control and postdeposition
      hydrothermal treatment. "Dead-end" permeation tests using dextran standards
      reveal the hydraulic characteristics and separations capability for the PCTE
      based TFC membranes. The results show that nanoparticle-based LbL surface
      modification of MF and UF rated media can produce TFC membranes with NF
      capabilities.

PMID- 24568093
TI  - Binding of the antitubercular pro-drug isoniazid in the heme access channel of
      catalase-peroxidase (KatG). A combined structural and metadynamics investigation.
AB  - Isonicotinic acid hydrazide (isoniazid or INH) is a front line antitubercular pro
      drug that is converted to its active form, isonicotinyl-NAD, by the bacterial
      catalase-peroxidase KatG. Understanding the role of KatG in the INH activation
      process has been hampered by a lack of knowledge of the actual drug binding site.
      In this work, we have investigated the binding of INH in the main access channel
      of KatG with a combination of molecular dynamics, using an enhanced-sampling
      technique (metadynamics), X-ray crystallography, and site-directed mutagenesis.
      The metadynamics simulations show that there are several weak drug binding sites
      along the access channel. Moreover, the simulations evidence that complete
      entrance to the heme active site is impeded by an aspartate residue (D141)
      located above the heme. This has been confirmed by structural and functional
      analysis of the D141A mutant, leading to the first X-ray crystallography evidence
      of INH at the heme access channel. 

PMID- 24568095
TI  - Role of IL-23 in the pathogenesis of psoriasis: a novel potential therapeutic
      target?
AB  - INTRODUCTION: Psoriasis is a chronic inflammatory skin disorder determined by the
      activation of several immune cells and resident tissue cells. Various cytokines
      mediate inflammatory signals, including IL-23, which is an important factor
      involved in the differentiation of T helper (Th17) cells. AREAS COVERED:
      Increasing evidence suggests that IL-23 is a central cytokine to the pathogenesis
      of psoriasis. An overview on both experimental and human data will be reported in
      order to support the hypothesis of a key pathogenic role of IL-23/Th17 axis.
      EXPERT OPINION: Targeting IL-23 might be a more selective, valid and effective
      therapeutic approach, which, potentially, may show important advantages in terms
      of long-term efficacy and safety in the treatment of psoriasis.

PMID- 24568097
TI  - False positives complicate ancient pathogen identifications using high-throughput
      shotgun sequencing.
AB  - BACKGROUND: Identification of historic pathogens is challenging since false
      positives and negatives are a serious risk. Environmental non-pathogenic
      contaminants are ubiquitous. Furthermore, public genetic databases contain
      limited information regarding these species. High-throughput sequencing may help
      reliably detect and identify historic pathogens. RESULTS: We shotgun-sequenced 8
      16th-century Mixtec individuals from the site of Teposcolula Yucundaa (Oaxaca,
      Mexico) who are reported to have died from the huey cocoliztli ('Great
      Pestilence' in Nahautl), an unknown disease that decimated native Mexican
      populations during the Spanish colonial period, in order to identify the
      pathogen. Comparison of these sequences with those deriving from the surrounding
      soil and from 4 precontact individuals from the site found a wide variety of
      contaminant organisms that confounded analyses. Without the comparative sequence
      data from the precontact individuals and soil, false positives for Yersinia
      pestis and rickettsiosis could have been reported. CONCLUSIONS: False positives
      and negatives remain problematic in ancient DNA analyses despite the application
      of high-throughput sequencing. Our results suggest that several studies claiming
      the discovery of ancient pathogens may need further verification. Additionally,
      true single molecule sequencing's short read lengths, inability to sequence
      through DNA lesions, and limited ancient-DNA-specific technical development
      hinder its application to palaeopathology.

PMID- 24568101
TI  - Gaining weight: livestock are bigger now at slaughter than in previous decades.

PMID- 24568099
TI  - Optimization for peptide sample preparation for urine peptidomics.
AB  - Analysis of native or endogenous peptides in biofluids can provide valuable
      insights into disease mechanisms. Furthermore, the detected peptides may also
      have utility as potential biomarkers for non-invasive monitoring of human
      diseases. The non-invasive nature of urine collection and the abundance of
      peptides in the urine makes analysis by high-throughput 'peptidomics' methods ,
      an attractive approach for investigating the pathogenesis of renal disease.
      However, urine peptidomics methodologies can be problematic with regards to
      difficulties associated with sample preparation. The urine matrix can provide
      significant background interference in making the analytical measurements that it
      hampers both the identification of peptides and the depth of the peptidomics read
      when utilizing LC-MS based peptidome analysis. We report on a novel adaptation of
      the standard solid phase extraction (SPE) method to a modified SPE (mSPE)
      approach for improved peptide yield and analysis sensitivity with LC-MS based
      peptidomics in terms of time, cost, clogging of the LC-MS column, peptide yield,
      peptide quality, and number of peptides identified by each method. Expense and
      time requirements were comparable for both SPE and mSPE, but more interfering
      contaminants from the urine matrix were evident in the SPE preparations (e.g.,
      clogging of the LC-MS columns, yellowish background coloration of prepared
      samples due to retained urobilin, lower peptide yields) when compared to the mSPE
      method. When we compared data from technical replicates of 4 runs, the mSPE
      method provided significantly improved efficiencies for the preparation of
      samples from urine (e.g., mSPE peptide identification 82% versus 18% with SPE; p
      = 8.92E-05). Additionally, peptide identifications, when applying the mSPE
      method, highlighted the biology of differential activation of urine peptidases
      during acute renal transplant rejection with distinct laddering of specific
      peptides, which was obscured for most proteins when utilizing the conventional
      SPE method. In conclusion, the mSPE method was found to be superior to the
      conventional, standard SPE method for urine peptide sample preparation when
      applying LC-MS peptidomics analysis due to the optimized sample clean up that
      provided improved experimental inference from the confidently identified
      peptides. 

PMID- 24568102
TI  - People are people.

PMID- 24568098
TI  - Functional probes of drug-receptor interactions implicated by structural studies:
      Cys-loop receptors provide a fertile testing ground.
AB  - Structures of integral membrane receptors provide valuable models for drug
      receptor interactions across many important classes of drug targets and have
      become much more widely available in recent years. However, it remains to be
      determined to what extent these images are relevant to human receptors in their
      biological context and how subtle issues such as subtype selectivity can be
      informed by them. The high precision structural modifications enabled by
      unnatural amino acid mutagenesis on mammalian receptors expressed in vertebrate
      cells allow detailed tests of predictions from structural studies. Using the Cys
      loop superfamily of ligand-gated ion channels, we show that functional studies
      lead to detailed binding models that, at times, are significantly at odds with
      the structural studies on related invertebrate proteins. Importantly, broad
      variations in binding interactions are seen for very closely related receptor
      subtypes and for varying drugs at a given binding site. These studies highlight
      the essential interplay between structural studies and functional studies that
      can guide efforts to develop new pharmaceuticals. 

PMID- 24568103
TI  - What is your diagnosis? Pancreatolithiasis.

PMID- 24568104
TI  - Diagnostic imaging in veterinary dental practice. Multilobular tumor of bone in
      the hard palate of a cat.

PMID- 24568105
TI  - ECG of the month. Atrial fibrillation due to hypokalemia in a horse.

PMID- 24568107
TI  - Pathology in practice. Adenocarcinoma of the proventriculus with liver metastasis
      and marked, diffuse chronic-active proventriculitis and ventriculitis with
      moderate M. ornithogaster infection in a budgerigar.

PMID- 24568106
TI  - Pathology in practice. Marked syringomyelia at the level of the lumbosacral
      intumescence.

PMID- 24568110
TI  - Effects of environmental enrichment on the behavior of shelter dogs.
AB  - OBJECTIVE: To determine the effect of food-toy enrichment combined with cage
      behavior training on desirable behaviors in shelter dogs and adoption rates.
      DESIGN: Randomized controlled clinical trial. ANIMALS: 107 dogs. PROCEDURES: Dogs
      placed up for adoption in a municipal shelter were randomly assigned to either an
      experimental group (n = 48) or control group (59). Experimental group subjects
      were exposed to an environmental enrichment and training protocol consisting of
      twice-daily cage-behavior training and daily provision of a food-filled toy. Cage
      behavior training included operant conditioning via positive reinforcement of
      desirable behaviors, including approaching the front of the cage, sitting or
      lying, and remaining quiet when approached. Behavioral observations were
      performed by a blinded observer in a scan-sampling technique on day 0 (first day
      on adoption floor) and again on day 3 for experimental (n = 26) and control (32)
      dogs. Body posture, location in cage, and other behavioral parameters were
      recorded. Adoption information and behavioral observation data were compared
      between groups. RESULTS: Compared with the control group, the experimental group
      had a significantly greater percentage of dogs with an increase in desirable
      behaviors of sitting or lying down (17/26 [65%] vs 7/32 [22%]) and being quiet
      (9/26 [35%] vs 4/32 [13%]) and a significantly greater percentage of dogs with a
      decrease in the undesirable behavior of jumping (15/26 [57%] vs 3/32 [9%]).
      Location in cage, fearfulness, and eye contact were not significantly different
      between groups. Survival analysis revealed no significant difference in adoption
      rates between groups. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that
      enrichment programs improve desirable behaviors and decrease undesirable behavior
      in shelter dogs, which may enhance welfare.

PMID- 24568111
TI  - Short-term outcome following partial or complete liver lobectomy with a
      commercially prepared self-ligating loop in companion animals: 29 cases (2009
      2012).
AB  - OBJECTIVE: To evaluate the clinical use of a self-ligating loop (SLL) for partial
      or complete liver lobectomy in a variety of companion animal species. DESIGN:
      Retrospective case series. ANIMALS: 22 dogs, 2 cats, 4 rabbits, and 1 ferret with
      partial or complete liver lobectomy performed with an SLL. PROCEDURES: Medical
      records of companion animal patients that underwent partial or complete liver
      lobectomy with an SLL between 2009 and 2012 at the Angell Animal Medical Center
      were reviewed, and signalment, intraoperative and postoperative complications,
      histologic diagnosis, hospital discharge (yes or no), time to hospital discharge,
      and short-term survival rate were recorded. Follow-up information was obtained
      through evaluation of medical records. RESULTS: 28 of 29 (97%) patients were
      discharged from the hospital and survived at least 5 days after discharge. Of the
      29 patients, 3 underwent 2 liver lobectomies. During 4 of 32 (12.5%) lobectomies,
      mild intraoperative bleeding occurred on the cut surface of the liver after
      transection. No transection performed with >= 2 SLLs resulted in notable
      intraoperative bleeding. One of 29 (3.4%) patients had evidence of postoperative
      hemoabdomen, which was successfully treated with a single packed RBC transfusion.
      Expansion of the SLL diameter from 8 to 15 cm was accomplished to allow for
      resection of larger masses. CONCLUSIONS AND CLINICAL RELEVANCE: Use of an SLL for
      partial or complete liver lobectomy in a variety of companion animal species was
      a safe technique and was associated with low morbidity and mortality rates.
      Expansion of the ligature loop diameter and use of multiple SLLs may be necessary
      for larger lobectomies.

PMID- 24568112
TI  - Biofilm-infected wounds in a dog.
AB  - CASE DESCRIPTION: A 4-year-old spayed female Mastiff was evaluated for treatment
      of chronic nonhealing pressure wounds over both elbow regions resulting from
      attempts at hypertrophic callus excision. CLINICAL FINDINGS: The wound bed
      granulation tissue was mottled red and yellow with hyperemic, rolled epithelial
      edges. The right wound communicated with a large fluid pocket along the thoracic
      wall. The dog had an inflammatory leukogram with a left shift. TREATMENT AND
      OUTCOME: The wounds were debrided, and tissue specimens were collected for
      histologic evaluation, microbial culture, and bacterial identification by means
      of molecular diagnostic techniques. The left wound was closed immediately.
      Calcium alginate rope with silver was packed into the right wound. Vacuum
      assisted closure was applied for 6 days. Debridement was repeated, and a
      thoracodorsal axial pattern flap was used to cover the wound. Systemic treatment
      with antimicrobials was initiated, and pressure over the elbow regions was
      relieved. Bacterial biofilms were identified histologically in tissue specimens
      from both wounds. Staphylococcus intermedius, Staphylococcus epidermidis, and
      Streptococcus canis were cultured and identified by 16S rRNA fragment sequencing.
      Pyrosequencing identified multiple bacterial species and no fungal organisms.
      Both wounds healed successfully. CLINICAL RELEVANCE: Biofilms are implicated in
      infected orthopedic implants in veterinary patients; however, this is the first
      report of a bacterial biofilm in chronic wounds in a dog. In human wound care,
      extensive debridement is performed to disrupt the biofilm; a multimodal treatment
      approach is recommended to delay reformation and help clear the infection. In
      this case, biofilm reformation was prevented by systemic treatment with
      antimicrobials, by reducing local pressure on the wounds, and by wound closure.

PMID- 24568113
TI  - Use of continuous electroencephalography for diagnosis and monitoring of
      treatment of nonconvulsive status epilepticus in a cat.
AB  - CASE DESCRIPTION: A 10-year-old domestic shorthair cat was evaluated because of
      presumed seizures. CLINICAL FINDINGS: The cat had intermittent mydriasis,
      hyperthermia, and facial twitching. Findings of MRI and CSF sample analysis were
      unremarkable, and results of infectious disease testing were negative. Treatment
      was initiated with phenobarbital, zonisamide, and levetiracetam; however, the
      presumed seizure activity continued. Results of analysis of continuous
      electroencephalographic recording indicated the cat had nonconvulsive status
      epilepticus. TREATMENT AND OUTCOME: The cat was treated with phenobarbital IV (6
      mg/kg [2.7 mg/lb] q 30 min during a 9-hour period; total dose, 108 mg/kg [49.1
      mg/lb]); treatment was stopped when a burst-suppression electroencephalographic
      pattern was detected. During this high-dose phenobarbital treatment period, an
      endotracheal tube was placed and the cat was monitored and received fluids,
      hetastarch, and dopamine IV. Continuous mechanical ventilation was not required.
      After treatment, the cat developed unclassified cardiomyopathy, azotemia, anemia,
      and pneumonia. These problems resolved during a 9-month period. CLINICAL
      RELEVANCE: Findings for the cat of this report indicated electroencephalographic
      evidence of nonconvulsive status epilepticus. Administration of a high total dose
      of phenobarbital and monitoring of treatment by use of electroencephalography
      were successful for resolution of the problem, and treatment sequelae resolved.

PMID- 24568114
TI  - Spontaneous regression of lumbar Hansen type 1 disk extrusion detected with
      magnetic resonance imaging in a dog.
AB  - CASE DESCRIPTION: A 3-year-old French Bulldog was evaluated because of acute
      signs of back pain and spastic paraparesis. CLINICAL FINDINGS: Neuroanatomic
      localization indicated a lesion in the T3-L3 spinal cord segment. Magnetic
      resonance imaging revealed extradural spinal cord compression at the ventral
      right aspect of the intervertebral disk space L3-4. On the basis of these
      findings, a diagnosis of sequestrated Hansen type 1 disk extrusion without
      extradural hemorrhage was made. TREATMENT AND OUTCOME: The dog was treated
      conservatively with cage rest, restricted exercise on a leash, and NSAIDs.
      Results of follow-up examination 5 weeks later indicated complete resolution of
      clinical signs, and results of repeated MRI indicated a 69% reduction in the
      volume of the herniated disk material. CLINICAL RELEVANCE: Findings for the dog
      of this report indicated spinal cord compression attributable to extruded
      intervertebral disk material resolved. Functional improvements in dogs with such
      problems may be partly attributable to spontaneous regression of intervertebral
      disk extrusions.

PMID- 24568115
TI  - Hemorrhage and blood loss-induced anemia associated with an acquired coagulation
      factor VIII inhibitor in a Thoroughbred mare.
AB  - CASE DESCRIPTION: A 23-year-old Thoroughbred mare was evaluated because of a
      coagulopathy causing hemoperitoneum, hematomas, and signs of blood loss-induced
      anemia. CLINICAL FINDINGS: The mare had tachycardia, pallor, hypoperfusion, and a
      large mass in the right flank. The mass was further characterized
      ultrasonographically as an extensive hematoma in the body wall with associated
      hemoabdomen. Coagulation testing revealed persistent, specific prolongation of
      the activated partial thromboplastin time (> 100 seconds; reference interval, 24
      to 44 seconds) attributable to severe factor VIII deficiency (12%; reference
      interval, 50% to 200%). On the basis of the horse's age, lack of previous signs
      of a bleeding diathesis, and subsequent quantification of plasma factor VIII
      inhibitory activity (Bethesda assay titer, 2.7 Bethesda units/mL), acquired
      hemophilia A was diagnosed. The medical history did not reveal risk factors or
      underlying diseases; thus, the development of inhibitory antibodies against
      factor VIII was considered to be idiopathic. TREATMENT AND OUTCOME: The mare was
      treated with 2 transfusions of fresh whole blood and fresh-frozen plasma.
      Immunosuppressive treatment consisting of dexamethasone and azathioprine was
      initiated. Factor VIII deficiency and signs of coagulopathy resolved, and the
      inhibitory antibody titer decreased. The mare remained healthy with no relapse
      for at least 1 year after treatment. CONCLUSIONS AND CLINICAL RELEVANCE: Horses
      may develop inhibitory antibodies against factor VIII that cause acquired
      hemophilia A. A treatment strategy combining transfusions of whole blood and
      fresh-frozen plasma and administration of immunosuppressive agents was effective
      and induced sustained remission for at least 1 year in the mare described here.

PMID- 24568116
TI  - Ultrathin, flexible organic-inorganic hybrid solar cells based on silicon
      nanowires and PEDOT:PSS.
AB  - Recently, free-standing, ultrathin, single-crystal silicon (c-Si) membranes have
      attracted considerable attention as a suitable material for low-cost,
      mechanically flexible electronics. In this paper, we report a promising
      ultrathin, flexible, hybrid solar cell based on silicon nanowire (SiNW) arrays
      and poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS). The free
      standing, ultrathin c-Si membranes of different thicknesses were produced by KOH
      etching of double-side-polished silicon wafers for various etching times. The
      processed free-standing silicon membranes were observed to be mechanically
      flexible, and in spite of their relatively small thickness, the samples tolerated
      the different steps of solar cell fabrication, including surface
      nanotexturization, spin-casting, dielectric film deposition, and metallization.
      However, in terms of the optical performance, ultrathin c-Si membranes suffer
      from noticeable transmission losses, especially in the long-wavelength region. We
      describe the experimental performance of a promising light-trapping scheme in the
      aforementioned ultrathin c-Si membranes of thicknesses as small as 5.7 MUm
      employing front-surface random SiNW texturization in combination with a back
      surface distribution of silver (Ag) nanoparticles (NPs). We report the
      enhancement of both the short-circuit current density (JSC) and the open-circuit
      voltage (VOC) that has been achieved in the described devices. Such enhancement
      is attributable to the plasmonic backscattering effect of the back-surface Ag
      NPs, which led to an overall 10% increase in the power conversion efficiency
      (PCE) of the devices compared to similar structures without Ag NPs. A PCE in
      excess of 6.62% has been achieved in the described devices having a c-Si membrane
      of thickness 8.6 MUm. The described device technology could prove crucial in
      achieving an efficient, low-cost, mechanically flexible photovoltaic device in
      the near future. 

PMID- 24568117
TI  - Activation of methane by FeO+: determining reaction pathways through temperature
      dependent kinetics and statistical modeling.
AB  - The temperature dependences of the rate constants and product branching ratios
      for the reactions of FeO(+) with CH4 and CD4 have been measured from 123 to 700
      K. The 300 K rate constants are 9.5 * 10(-11) and 5.1 * 10(-11) cm(3) s(-1) for
      the CH4 and CD4 reactions, respectively. At low temperatures, the Fe(+) +
      CH3OH/CD3OD product channel dominates, while at higher temperatures,
      FeOH(+)/FeOD(+) + CH3/CD3 becomes the majority channel. The data were found to
      connect well with previous experiments at higher translational energies. The
      kinetics were simulated using a statistical adiabatic channel model (vibrations
      are adiabatic during approach of the reactants), which reproduced the
      experimental data of both reactions well over the extended temperature and energy
      ranges. Stationary point energies along the reaction pathway determined by ab
      initio calculations seemed to be only approximate and were allowed to vary in the
      statistical model. The model shows a crossing from the ground-state sextet
      surface to the excited quartet surface with large efficiency, indicating that
      both states are involved. The reaction bottleneck for the reaction is found to be
      the quartet barrier, for CH4 modeled as -22 kJ mol(-1) relative to the sextet
      reactants. Contrary to previous rationalizations, neither less favorable spin
      crossing at increased energies nor the opening of additional reaction channels is
      needed to explain the temperature dependence of the product branching fractions.
      It is found that a proper treatment of state-specific rotations is crucial. The
      modeled energy for the FeOH(+) + CH3 channel (-1 kJ mol(-1)) agrees with the
      experimental thermochemical value, while the modeled energy of the Fe(+) + CH3OH
      channel (-10 kJ mol(-1)) corresponds to the quartet iron product, provided that
      spin-switching near the products is inefficient. Alternative possibilities for
      spin switching during the reaction are considered. The modeling provides unique
      insight into the reaction mechanisms as well as energetic benchmarks for the
      reaction surface. 

PMID- 24568118
TI  - Screen3D: a novel fully flexible high-throughput shape-similarity search method.
AB  - 3D shape- or volume-based virtual screening is a broadly used approach in drug
      discovery. In recent years a large number of publications have appeared in which
      these tools were compared not only to competitive methods but to docking studies
      as well. Studies often showed that the effectiveness of docking could be highly
      variable due to a large number of possible confounding factors, while ligand
      based, shape-based approaches were more consistent. Here, we describe a novel,
      fully flexible shape-based virtual screening algorithm that does not require
      previous 3D conformation or conformer generation. Due to its solid consistency it
      can easily be used on desktop computers by non-expert scientists. The algorithm
      is demonstrated in a study for the investigation of beta-secretase inhibitors and
      benchmarked on the Directory of Useful Decoys data set. 

PMID- 24568119
TI  - High prevalence and variability of CTX-M-15-producing and fluoroquinolone
      resistant Escherichia coli observed in stray dogs in rural Angola.
AB  - Antimicrobial resistance (AMR) represents a serious problem globally, but it is
      especially pronounced in the tropics, where pressure of infectious diseases is
      high. We examined resistance in Escherichia coli colonizing gastrointestinal
      tracts of 17 dogs which have never received antimicrobial treatment, living in
      central rural Angola. Emphasis was placed on extended-spectrum beta-lactamases
      (ESBL) and plasmid-mediated quinolone resistance (PMQR). Resistance-carrying
      plasmids were characterized in size, group of incompatibility and ability to
      conjugate. Isolates were compared by their pulsed-field gel electrophoresis
      (PFGE) profiles. Detailed description of 19 E. coli isolates with either ESBL or
      PMQR genes carried on multiresistant plasmids of different groups of
      incompatibility indicates that dogs, despite never being treated by antibiotics,
      are important reservoirs and transmitters of AMR in the study area. 

PMID- 24568120
TI  - An outpatient antibacterial stewardship intervention during the journey to JCI
      accreditation.
AB  - BACKGROUND: Antibacterial overuse, misuse and resistance have become a major
      global threat. The Joint Commission International (JCI) accreditation standards
      include quality improvement and patient safety, which is exemplified by
      antimicrobial stewardship. There are currently few reports on interventions to
      improve the quality of outpatient antibacterial prescribing. METHODS: A before
      after intervention study, aiming at antibacterial use in outpatients, was
      performed in a university-affiliated hospital with 2.8 million outpatient visits
      annually during the journey to JCI accreditation (March of 2012 - March of 2013).
      Comprehensive intervention measures included formulary adjustment, classification
      management, motivational, information technological, educational and
      organizational measures. A defined daily dose (DDD) methodology was applied.
      Pharmacoeconomic data and drug-related problems (DRPs) were statistically
      compared between the two phases. RESULTS: The variety of antibacterials available
      in outpatient pharmacy decreased from 38 to 16. The proportion of antibacterial
      prescriptions significantly decreased (12.7% versus 9.9%, P < 0.01). The
      proportion of prescriptions containing the restricted antibacterials was 30.4% in
      the second phase, significantly lower than the value of 44.7% in the first phase
      (P < 0.01). The overall proportion of oral versus all antibacterial prescriptions
      increased (94.0% to 100%, P < 0.01) when measured as defined daily doses.
      Statistically significant increases in relative percentage of DDDs of oral
      antibacterials (i.e., DDDs of individual oral antibacterial divided by the sum of
      DDDs of all antibacterials) were observed with moxifloxacin, levofloxacin,
      cefuroxime axetil, ornidazole, clindamycin palmitate, cefaclor, amoxicillin and
      clarithromycin. Occurrence rate of DRPs decreased from 13.6% to 4.0% (P < 0.01),
      with a larger decrease seen in surgical clinics (surgical: 19.5% versus 5.6%;
      internal medicine: 8.4% versus 2.8%, P < 0.01). The total expenditure on
      antibacterials for outpatients decreased by 34.7% and the intervention program
      saved about 6 million Chinese Yuan Renminbi (CNY) annually. CONCLUSION: The one
      year intervention program on outpatient antibacterial use during the journey to
      JCI accreditation reduced the expenditure on antibacterials, improved the
      appropriateness of antibacterial prescriptions. Quality improvements need
      integrated multifaceted intervention measures and long-term adherence to the
      antibiotic stewardship. Approach of i.v. to oral antibacterial switch,
      classification management, and motivational measures may play the most efficient
      role in changing antibacterial prescription practices.

PMID- 24568121
TI  - Dietary exposure of Hong Kong adults to acrylamide: results of the first Hong
      Kong Total Diet Study.
AB  - Acrylamide is a processing contaminant in food formed during cooking at high
      temperature, such as frying and baking. To assess the associated health risk of
      the Hong Kong population, the dietary exposure of Hong Kong adults to acrylamide
      was estimated in the first Hong Kong Total Diet Study (TDS), where food samples
      were collected and prepared "as consumed". A total of 532 composite food samples
      were analysed for acrylamide using LC-MS/MS. Dietary exposures were estimated by
      combining the analytical results with the food consumption data of the Hong Kong
      adults. The mean and 95th percentile exposures to acrylamide of the Hong Kong
      population were 0.213 and 0.538 MUg kg-1 body weight (bw) day-1, respectively,
      and their margins of exposure (MOEs) were all below 10,000. The main dietary
      source of acrylamide was "Vegetables and their products" (52.4% of the total
      exposure), particularly stir-fried vegetables (44.9%), followed by "Cereals and
      their products" (14.7%) and "Mixed dishes" (9.43%). The study findings suggest
      that the relatively low figures for MOE for a genotoxic carcinogen may indicate
      human health concern of the Hong Kong population. Efforts should continue to be
      made in the interest of reducing acrylamide levels in food locally.

PMID- 24568123
TI  - Imaging of distribution of topically applied drug molecules in mouse skin by
      combination of time-of-flight secondary ion mass spectrometry and scanning
      electron microscopy.
AB  - In the development of topical drugs intended for local effects in the skin, one
      of the major challenges is to achieve drug penetration through the external
      barrier of the skin, stratum corneum, and secure exposure to the viable skin
      layers. Mass spectrometric imaging offers an opportunity to study drug
      penetration in a variety of skin models by mapping the spatial distribution in
      different skin layers after topical application of the drug. In this study, we
      used time-of-flight secondary ion mass spectrometry (TOF-SIMS) and scanning
      electron microscopy (SEM) to image the distribution of three drug molecules in
      skin tissue cross sections of inflamed mouse ear. The three compounds,
      roflumilast, tofacitinib, and ruxolitinib, were topically administered to the
      mouse ears, which were subsequently cryosectioned and thawed for the analyses.
      The results reveal that the combination of TOF-SIMS and SEM was beneficial for
      interpretation of drug distribution. SEM identified the different skin layers,
      while spatial distributions of all three compounds could be visualized by TOF
      SIMS, showing that the drug was primarily distributed into, or on the top of, the
      stratum corneum. Imaging of endogenous skin components like cholesterol,
      phospholipids, ceramides, and free fatty acids showed distributions in good
      agreement with the literature. One limitation of the TOF-SIMS method is
      sensitivity, typically allowing for analysis in the millimolar range rather than
      the pharmacologically relevant micromolar range. However, the data presented
      demonstrate the potential of the technique for studying the penetration of drugs
      with different physicochemical properties in skin. 

PMID- 24568122
TI  - A system of vectors for Bacillus subtilis spore surface display.
AB  - BACKGROUND: Bacterial spores have been utilized as platforms for protein display.
      The best studied display systems are based on Bacillus subtilis spores in which
      several coat proteins have successfully been used as anchors for heterologous
      protein. Increasing knowledge about spore coat structure enables selection of new
      anchor proteins such as CotZ and CgeA. Here we describe a system of vectors for
      display of proteins on the surface of B. subtilis spores. RESULTS: We have
      designed and constructed a set of 16 vectors for ectopic integration which can be
      used for spore surface display of heterologous proteins. There is a selection of
      five coat proteins: CotB, CotC, CotG, CotZ and CgeA which can be used for
      construction of fusions. Three of these (CotB, CotC and CotG) enable obtaining N
      terminal and C-terminal fusions and other two (CotZ and CgeA) are designed to
      produce C-terminal fusions only. All the vectors enable introduction of an
      additional peptide linker between anchor and displayed protein to enhance surface
      display. As a selection marker trophic genes are used. Additionally we describe
      an example application of presented vector system to display CagA protein of
      Helicobacter pylori in fusion with CgeA spore coat protein. CONCLUSIONS:
      Described system of vectors is a versatile tool for display of heterologous
      proteins on the surface of B. subtilis spores. Such recombinant spores can be
      further used as for example biocatalysts or antigen-carriers in vaccine
      formulations. The lack of antibiotic resistance genes in the system makes such
      spores an interesting option for applications in which a possible release to the
      environment can occur.

PMID- 24568124
TI  - A critical appraisal of probiotics (as drugs or food supplements) in
      gastrointestinal diseases.
AB  - Probiotics may be registered as food supplements or drugs. This article
      summarizes differences in European regulations of probiotics registered as food
      supplements and drugs, as well as issues related to the quality of probiotic
      products. For registration as a drug, the European Medicines Agency demands
      extensive and detailed quality, efficacy and safety evidence; whereas compulsory
      analyses requested for food supplements consist only in a nutritional analysis.
      As a result, the quality of those probiotics registered as drugs, compared to
      food supplements, is in general controlled with higher standards. Despite these
      differences and whatever the status of the probiotic product, its efficacy and
      safety has to be documented in well conducted randomized controlled trials
      (RCTs). Furthermore, this paper reviews recent evidence on the use of probiotics
      for gastrointestinal diseases, evaluating all the existing information up to
      January 2014. In all eligible published studies in which use of probiotics for
      gastrointestinal diseases were investigated and reported, no language limitations
      were applied. Special focus is placed on RCTs (or their meta-analyses) showing
      positive results, so that the findings may be applicable to everyday clinical
      practice. Currently, the best documented clinical areas appear to be probiotics
      efficacy for the treatment of acute gastroenteritis in children and for the
      prevention of antibiotic-associated diarrhea both in children and in adults. In
      other gastrointestinal conditions, some promising observations are emerging, but
      no definitive conclusions can be reached at present.

PMID- 24568126
TI  - Triggering the generation of an iron(IV)-oxo compound and its reactivity toward
      sulfides by Ru(II) photocatalysis.
AB  - The preparation of [Fe(IV)(O)(MePy2tacn)](2+) (2, MePy2tacn = N-methyl-N,N-bis(2
      picolyl)-1,4,7-triazacyclononane) by reaction of [Fe(II)(MePy2tacn)(solvent)](2+)
      (1) and PhIO in CH3CN and its full characterization are described. This compound
      can also be prepared photochemically from its iron(II) precursor by irradiation
      at 447 nm in the presence of catalytic amounts of [Ru(II)(bpy)3](2+) as
      photosensitizer and a sacrificial electron acceptor (Na2S2O8). Remarkably, the
      rate of the reaction of the photochemically prepared compound 2 toward sulfides
      increases 150-fold under irradiation, and 2 is partially regenerated after the
      sulfide has been consumed; hence, the process can be repeated several times. The
      origin of this rate enhancement has been established by studying the reaction of
      chemically generated compound 2 with sulfides under different conditions, which
      demonstrated that both light and [Ru(II)(bpy)3](2+) are necessary for the
      observed increase in the reaction rate. A combination of nanosecond time-resolved
      absorption spectroscopy with laser pulse excitation and other mechanistic studies
      has led to the conclusion that an electron transfer mechanism is the most
      plausible explanation for the observed rate enhancement. According to this
      mechanism, the in-situ-generated [Ru(III)(bpy)3](3+) oxidizes the sulfide to form
      the corresponding radical cation, which is eventually oxidized by 2 to the
      corresponding sulfoxide. 

PMID- 24568125
TI  - Post-intervention effects on screen behaviours and mediating effect of parental
      regulation: the HEalth In Adolescents study--a multi-component school-based
      randomized controlled trial.
AB  - BACKGROUND: To improve effectiveness of future screen behaviour interventions,
      one needs to know whether an intervention works via the proposed mediating
      mechanisms and whether the intervention is equally effective among subgroups.
      Parental regulation is identified as a consistent correlate of screen behaviours,
      but prospective evidence as well as the mediation role of parental regulation is
      largely lacking. This study investigated post-intervention main effects on screen
      behaviours in the HEIA-intervention--a Norwegian school-based multiple-behaviour
      study, as well as mediation effects of parental regulation by adolescents' and
      parents' report. In addition, moderating effects of gender and weight status on
      the intervention and mediating effects were explored. METHODS: Participating
      schools were randomized to control (n=25) or intervention (n=12) condition.
      Adolescents (n=908 Control; 510 Intervention) self-reported their weekday and
      weekend TV-viewing and computer/game-use. Change in adolescents' behaviours was
      targeted through school and parents. Adolescents, mothers (n=591 Control; 244
      Interventions) and fathers (n=469 Control; 199 Intervention) reported parental
      regulation of the screen behaviours post-intervention (at 20 month). The product
      of-coefficient test using linear regression analysis was conducted to examine
      main and mediating effects. RESULTS: There was no intervention effect on the
      screen behaviours in the total sample. Gender moderated effect on weekend
      computer/game-use, while weight status moderated the effect on weekday TV-viewing
      and computer/game-use. Stratified analyses showed a small favourable intervention
      effect on weekday TV-viewing among the normal weight. Parental regulation did not
      mediate change in the screen behaviours. However, stronger parental regulation
      was associated with less TV-viewing and computer/game-use with effects being
      conditional on adolescents' versus parental reports. Parental regulation of the
      screen behaviours, primarily by the parental report, was associated with change
      in the respective behaviours. CONCLUSION: Multiple behaviour intervention may not
      affect all equally well, and the effect may differ by weight status and gender.
      In future interventions parents should be encouraged to regulate their
      adolescents' TV-viewing and computer/game-use on both weekdays and weekends as
      parental regulation was identified as a determinant of these screen behaviours.
      However, future intervention studies may need to search for more effective
      intervention strategies targeting parental regulation. TRIAL REGISTRATION:
      Current Controlled Trials ISRCTN98552879.

PMID- 24568127
TI  - Fabrication techniques for ocular prostheses--an overview.
AB  - The goals of treatment with ocular prostheses are to restore facial aesthetics
      and self-esteem to anophthalmic patients. Fabricated in acrylic resin, artificial
      eyes should be aesthetically pleasing, scratch-resistant, and adequately
      polished. Use of a prosthesis without such characteristics can lead to
      psychological damage, as well as infection and inflammation due to the
      accumulation of microorganisms and other substances on an irregularly shaped
      prosthesis. The present literature review describes the different techniques for
      fabricating ocular prostheses. Reproduction of the iris color and color stability
      are important factors that promote adequate aesthetics. The fabrication of an
      individual ocular prosthesis in acrylic resin provides satisfactory aesthetic
      results because the impression process establishes the defect contour.
      Additionally, the iris and sclera can be individually characterized. As the
      techniques, materials, and manufacturing methods for ocular prostheses continue
      to evolve, the aesthetics and functionality of prostheses will also improve.

PMID- 24568129
TI  - Age dependence of hematopoietic progenitor survival and chemokine family gene
      induction after gamma irradiation in bone marrow tissue in C3H/He mice.
AB  - Age at exposure is a critical factor that influences the risk of radiation
      induced leukemia, which arises from hematopoietic stem and progenitor cells.
      However, little is known about the effect of age on the radiation response of
      these cells. In this study, we examined the radiation response of hematopoietic
      stem and progenitor cells in infant (1-week-old), juvenile (3-week-old), and
      adult (8- and 14-week-old) C3H/He mice, which are susceptible to radiation
      induced myeloid leukemia. We first observed an age-dependent increase in the
      radioresistance of hematopoietic stem and progenitor cells after in vivo
      irradiation. However, in vitro irradiation of progenitor cells did not show any
      age differences, suggesting that radiation sensitivity in vivo is dependent on
      the bone marrow microenvironment rather than to intrinsic properties of
      progenitors themselves. Expression profiles of bone marrow tissues identified
      chemokine and cytokine family genes, whose expression differed between infant and
      adult tissues at time points before and after irradiation. Among the selected
      thirteen cytokines reported to be radioprotective, we observed increased
      expression of Csf1, Csf2, Cxcl12, Fgf1, Fgf7, Il1a, Il1b and Kitl after
      irradiation, mostly in adult tissues. Specifically, Csf2, Fgf1 and Il1b
      expression, as revealed by qPCR, were significantly enhanced in adult bone marrow
      tissue after irradiation, but were unresponsive to irradiation in infant tissue.
      These results suggest that the higher susceptibility of infant hematopoietic stem
      and progenitor cells to the cell killing effect of ionizing radiation may be
      attributed to a failure to induce a subset of radioprotective cytokines in the
      immature bone marrow microenvironment. 

PMID- 24568128
TI  - Proton irradiation augments the suppression of tumor progression observed with
      advanced age.
AB  - Proton radiation is touted for improved tumor targeting, over standard gamma
      radiation, due to the physical advantages of ion beams for radiotherapy. Recent
      studies from our laboratory demonstrate that in addition to these targeting
      advantages, proton irradiation can inhibit angiogenic and immune factors critical
      to "hallmark" processes that impact cancer progression, thereby modulating tumor
      development. Outside the therapeutic utilization of protons, high-energy protons
      constitute a principal component of galactic cosmic rays and thus are a
      consideration in carcinogenesis risk for space flight. Given that proton
      irradiation modulates fundamental biological processes known to decrease with
      aging (e.g. angiogenesis and immunogenicity), we investigated how proton
      irradiation impacts tumor advancement as a function of host age, a question with
      both therapeutic and carcinogenesis implications. Tumor lag time and growth
      dynamics were tracked, after injection of murine Lewis lung carcinoma (LLC) cells
      into syngeneic adolescent (68 day) vs. old (736 day) C57BL/6 mice with or without
      coincident irradiation. Tumor growth was suppressed in old compared to adolescent
      mice. These differences were further modulated by proton irradiation (1 GeV),
      with increased inhibition and a significant radiation-altered molecular
      fingerprint evident in tumors grown in old mice. Through global transcriptome
      analysis, TGFbeta1 and TGFbeta2 were determined to be key players that
      contributed to the tumor dynamics observed. These findings suggest that old hosts
      exhibit a reduced capacity to support tumor advancement, which can be further
      reduced by proton irradiation. 

PMID- 24568133
TI  - Sequential hydrozirconation/cyclization of dienes, a new route toward trans 2
      substituted vinylcyclopentanes.
AB  - The diastereoselective synthesis of trans-2-substituted vinylcyclopentanes is
      described. The method is based on the intramolecular coupling of 7-methoxy-1,5
      dienes involving a sequential activation of the C?C double bonds via
      hydrozirconation and TMSOTf-promoted allylation. 

PMID- 24568131
TI  - Bone marrow transplantation helps restore the intestinal mucosal barrier after
      total body irradiation in mice.
AB  - Bone marrow transplantation (BMT) substantially improves 10-day survival after
      total body irradiation (TBI), consistent with an effect on intestinal radiation
      death. Total body irradiation, in addition to injuring the intestinal epithelium,
      also perturbs the mucosal immune system, the largest immune system in the body.
      This study focused on how transplanted bone marrow cells (BMCs) help restore
      mucosal immune cell populations after sublethal TBI (8.0 Gy). We further
      evaluated whether transplanted BMCs: (a) home to sites of radiation injury using
      green fluorescent protein labeled bone marrow; and (b) contribute to restoring
      the mucosal barrier in vivo. As expected, BMT accelerated recovery of peripheral
      blood (PB) cells. In the intestine, BMT was associated with significant early
      recovery of mucosal granulocytes (P = 0.005). Bone marrow transplantation did not
      affect mucosal macrophages or lymphocyte populations at early time points, but
      enhanced the recovery of these cells from day 14 onward (P = 0.03). Bone marrow
      transplantation also attenuated radiation-induced increase of intestinal CXCL1
      and restored IL-10 levels (P = 0.001). Most importantly, BMT inhibited the post
      radiation increase in intestinal permeability after 10 Gy TBI (P = 0.02) and
      modulated the expression of tight junction proteins (P = 0.01-0.05). Green
      fluorescent protein-positive leukocytes were observed both in intestinal tissue
      and in PB. These findings strongly suggest that BMT, in addition to enhancing
      general hematopoietic and immune system recovery, helps restore the intestinal
      immune system and enhances intestinal mucosal barrier function. These findings
      may be important in the development and understanding of strategies to alleviate
      or treat intestinal radiation toxicity. 

PMID- 24568132
TI  - Association between serum uric acid levels and cardiovascular disease in middle
      aged and elderly Chinese individuals.
AB  - BACKGROUND: A link between uric acid (UA) levels and cardiovascular diseases has
      been previously reported. However, its importance as a risk factor is still
      controversial. This study sought to determine whether elevated serum uric acid
      levels are associated with cardiovascular disease (CVD) in middle-aged and
      elderly Chinese individuals. METHODS: We conducted a population-based cross
      sectional study in Shanghai, with a total of 8510 participants aged >=40 years.
      The CVD included diagnosed coronary heart disease (CHD) and stroke. MetS was
      defined according to the updated National Cholesterol Education Program Adult
      Treatment Panel III criteria for Asian Americans. RESULTS: Uric acid levels were
      positively associated with BMI, waist circumference, triglycerides, systolic
      blood pressure, diastolic blood pressure, glycohemoglobin, fasting plasma
      glucose, postprandial 2-hour plasma glucose (all P < 0.05), and negatively
      associated with HDL-cholesterol (P < 0.001). The prevalence of CVD significantly
      increased with increasing quartiles of UA in those without MetS group (p trend <
      0.001), but not necessarily increased in those with MetS. After adjustment for
      metabolic syndrome and other cardiovascular risk factors, multivariate logistic
      regression analysis showed that odds ratios (OR) for CHD, stroke, and CVD in
      those in the fourth quartiles were 2.34 (95% confidence interval [CI] 1.73 to
      3.45), 2.18 (95% CI 1.86 to 3.28), and 2.16 (95% CI 1.80 to 3.29), respectively,
      compared with those in the first quartile of UA. CONCLUSIONS: Elevated serum uric
      acid level was associated with CVD, independent of conventional cardiovascular
      disease risk factors and metabolic syndrome.

PMID- 24568134
TI  - Cerium(IV) ammonium nitrate mediated three-component alpha-allylation of imine
      surrogates.
AB  - A general and practical CAN-mediated oxidative radical alpha-coupling reaction of
      various imine surrogates with allylsilanes has been described. This
      multicomponent process affords beta-allylated alpha-carbamido ethers as stable
      imine precursors in respectable yields under mild conditions. 

PMID- 24568135
TI  - Alkynyliodonium salt mediated alkynylation of azlactones: fast access to C(alpha)
      tetrasubstituted alpha-amino acid derivatives.
AB  - An efficient electrophilic alkynylation of azlactones (oxazol-5(4H)-ones) is
      developed using alkynyl(phenyl)iodonium salts as the electrophilic alkyne source.
      After remarkably short reaction times, the desired alkyne functionalized
      azlactones are obtained in 60-97% yield and can be transformed easily into a
      variety of quaternary alpha-amino acid derivatives. 

PMID- 24568130
TI  - Radiation-induced alterations in mitochondria of the rat heart.
AB  - Radiation therapy for the treatment of thoracic cancers may be associated with
      radiation-induced heart disease (RIHD), especially in long-term cancer survivors.
      Mechanisms by which radiation causes heart disease are largely unknown. To
      identify potential long-term contributions of mitochondria in the development of
      radiation-induced heart disease, we examined the time course of effects of
      irradiation on cardiac mitochondria. In this study, Sprague-Dawley male rats
      received image-guided local X irradiation of the heart with a single dose ranging
      from 3-21 Gy. Two weeks after irradiation, left ventricular mitochondria were
      isolated to assess the dose-dependency of the mitochondrial permeability
      transition pore (mPTP) opening in a mitochondrial swelling assay. At time points
      from 6 h to 9 months after a cardiac dose of 21 Gy, the following analyses were
      performed: left ventricular Bax and Bcl-2 protein levels; apoptosis;
      mitochondrial inner membrane potential and mPTP opening; mitochondrial mass and
      expression of mitophagy mediators Parkin and PTEN induced putative kinase-1 (PINK
      1); mitochondrial respiration and protein levels of succinate dehydrogenase A
      (SDHA); and the 70 kDa subunit of complex II. Local heart irradiation caused a
      prolonged increase in Bax/Bcl-2 ratio and induced apoptosis between 6 h and 2
      weeks. The mitochondrial membrane potential was reduced until 2 weeks, and the
      calcium-induced mPTP opening was increased from 6 h up to 9 months. An increased
      mitochondrial mass together with unaltered levels of Parkin suggested that
      mitophagy did not occur. Lastly, we detected a significant decrease in succinate
      driven state 2 respiration in isolated mitochondria from 2 weeks up to 9 months
      after irradiation, coinciding with reduced mitochondrial levels of succinate
      dehydrogenase A. Our results suggest that local heart irradiation induces long
      term changes in cardiac mitochondrial membrane functions, levels of SDH and state
      2 respiration. At any time after exposure to radiation, cardiac mitochondria are
      more prone to mPTP opening. Future studies will determine whether this makes the
      heart more susceptible to secondary stressors such as calcium overload or
      ischemia/reperfusion. 

PMID- 24568136
TI  - Glycaemic Control in Cardiac Surgery Patients: a Double-Edged Sword.
AB  - Glycaemic management is of paramount importance in the cardiac surgery setting. A
      growing body of evidence confirms a J-shaped relationship between blood glucose
      (BG) level and perioperative morbidity and mortality. On one hand, acute
      hypoglycaemia causes irreversible cerebral damage. On the other hand,
      hyperglycaemia increases the risk of infections, acute kidney injury, atrial
      fibrillation, low cardiac output syndrome, cerebrovascular accidents and
      cognitive impairment. Also, high BG variability, even within the therapeutic
      window, may deteriorate the outcome. Therefore, moderate perioperative insulin
      management is usually recommended, with target BG adjusted to individual needs
      and possibilities. Continuous BG monitoring is a promising tool that should help
      practitioners in everyday decision-making process of glycaemic control. This
      review summarises the current evidence-based knowledge on the perioperative
      management of hyperglycaemia. 

PMID- 24568137
TI  - Bovine pericardial reconstruction of the diaphragm after a heart transplant.
AB  - Diaphragmatic hernias are a known complication of explanting a left ventricular
      assist device. The increasing use of left ventricular assist devices has resulted
      in an increased risk of this complication. We present the case of a patient who
      presented with diaphragmatic hernias on routine follow-up after a heart
      transplant. A left thoracotomy was performed to expose and reduce the hernia
      using a bovine pericardial patch to repair the defect. This biomaterial
      represents a viable alternative to traditional GORE-TEX patches with the
      probability of decreased infectious complications. 

PMID- 24568138
TI  - Epigenetics in the pathogenesis of rheumatoid arthritis.
AB  - An increasing number of studies show that besides the inherited genetic
      architecture (that is, genomic DNA), various environmental factors significantly
      contribute to the etiology of rheumatoid arthritis. Epigenetic factors react to
      external stimuli and form bridges between the environment and the genetic
      information-harboring DNA. Epigenetic mechanisms are implicated in the final
      interpretation of the encoded genetic information by regulating gene expression,
      and alterations in their profile influence the activity of the immune system.
      Overall, epigenetic mechanisms further increase the well-known complexity of
      rheumatoid arthritis by providing additional subtle contributions to rheumatoid
      arthritis susceptibility. Although there are controversies regarding the
      involvement of epigenetic and genetic factors in rheumatoid arthritis etiology,
      it is becoming obvious that the two systems (genetic and epigenetic) interact
      with each other and are ultimately responsible for rheumatoid arthritis
      development. Here, epigenetic factors and mechanisms involved in rheumatoid
      arthritis are reviewed and new, potential therapeutic targets are discussed. 

PMID- 24568140
TI  - Reference values for isometric muscle force among workers for the Netherlands: a
      comparison of reference values.
AB  - BACKGROUND: Muscle force is important for daily life and sports and can be
      measured with a handheld dynamometer. Reference values are employed to quantify a
      subject's muscle force. It is not unambiguous whether reference values can be
      generalized to other populations. Objectives in this study were; first to confirm
      the reliability of the utilization of hand-held dynamometers for isometric
      strength measurement; second to determine reference values for a population of
      Dutch workers; third to compare these values with those of a USA population.
      METHODS: 462 Healthy working subjects (259 male, 203 female) were included in
      this study. Their age ranged from 20 to 60 years with a mean (sd) of 41 (11)
      years. Muscle force values from elbow flexion and extension, knee flexion and
      extension, and shoulder abduction were measured with the break method using a
      MicroFet 2 hand-held dynamometer. Reliability was analyzed by calculating ICC's
      and limits of agreement. Muscle force expressed in Newton, means, and confidence
      intervals were determined for males and females in age groups ranging from twenty
      to sixty years old. Regression equations and explained variances were calculated
      from weight, height, age, and gender. The mean values and 95% CI were compared to
      the results from other studies. RESULTS: Reliability was good; the ICC ranged
      between 0.83 to 0.94. The explained variance ranged from 0.25 to 0.51. Comparison
      of data for the Dutch population mean muscle force values with those from the USA
      revealed important differences between muscle force reference values for the
      American and Dutch populations. CONCLUSIONS: Muscle force measurements
      demonstrate a sound reliability. Reference values and regressions equations are
      made available for the Dutch population. Comparison with other studies indicates
      that reference values differ between countries.

PMID- 24568139
TI  - Giardiosis and other enteropathogenic infections: a study on diarrhoeic calves in
      Southern Germany.
AB  - BACKGROUND: Diarrhoea induces massive problems in the rearing of calves. The aim
      of the study was to obtain current data about the frequency of Giardia spp.,
      Cryptosporidium spp. and Eimeria spp. in diarrhoeic calves in Southern Germany
      with the particular focus on giardiosis. RESULTS: 1564 samples were analysed for
      the three pathogens using microscopical methods. Giardia spp. was detectable in
      112/1564 samples (7.2%). The mean age was 46.5 days and the odds of being
      infected with Giardia spp. increased slowly up to 8 times from about 12 days to
      30 days of age. There appeared to be no seasonal influence on the frequency of
      Giardia spp. A mono-infection with Giardia spp. was diagnosed in 46 calves (2.9%)
      whereas 15 calves (1.0%) had a mixed-infection with Cryptosporidium spp. and 51
      calves (3.3%) with Eimeria spp. Cryptosporidium spp. and Eimeria spp. could be
      detected in 646/1564 samples (41.3%) and 208/1564 samples (13.3%), respectively,
      with a mean age of 11.3 and 55.0 days, respectively. The odds of being infected
      with Cryptosporidium spp. increased up to 4.5 times until an age of 10 days.
      After that the odds decreased continuously and was approaching zero at about 30
      days. The odds of being infected with Eimeria spp. increased continuously up to
      30 times from about 20 days to 60 days of age. There appeared to be no
      significant seasonal influence on the frequency of Cryptosporidium spp.; but
      there was one for Eimeria spp.: the odds of being infected with Eimeria spp. in
      March and April decreased by about half and increased up to 2.3 times between
      July and September. Additionally, as requested by the veterinarians, 1282 of
      those samples were analysed for E. coli, Rota-, Coronavirus and Cryptosporidium
      spp. using an ELISA. Obtained frequencies for these pathogens were 0.9%, 37.8%,
      3.4% and 45.3% with a mean age of 24.8 days, 12.1 days, 9.0 days and 12.1 days,
      respectively. CONCLUSIONS: The results indicate that in Southern Germany in
      addition to Eimeria spp., Giardia spp. seems to play a contributing role in
      diarrhoea in older calves, whereas Cryptosporidium spp. and Rotavirus are mostly
      relevant in young calves.

PMID- 24568142
TI  - Challenges and strategies for cohort retention and data collection in an
      indigenous population: Australian Aboriginal Birth Cohort.
AB  - BACKGROUND: Longitudinal prospective birth cohort studies are pivotal to
      identifying fundamental causes and determinants of disease and health over the
      life course. There is limited information about the challenges, retention, and
      collection strategies in the study of Indigenous populations. The aim is to
      describe the follow-up rates of an Australian Aboriginal Birth Cohort study and
      how they were achieved. METHODS: Participants were 686 babies enrolled between
      January 1987 and March 1990, born to a mother recorded in the Delivery Suite
      Register of the Royal Darwin Hospital (RDH) as a self-identified Aboriginal. The
      majority of the participants (70%) resided in Northern Territory within rural,
      remote and very remote Aboriginal communities that maintain traditional
      connections to their land and culture. The Aboriginal communities are within a
      sparsely populated (0.2 people/ km2) area of approximately 900,000 km2 (347 sq
      miles), with poor communication and transport infrastructures. Follow-ups
      collecting biomedical and lifestyle data directly from participants in over 40
      locations were conducted at 11.4 years (Wave-2) and 18.2 years (Wave-3), with
      Wave-4 follow-up currently underway. RESULTS: Follow-ups at 11 and 18 years of
      age successfully examined 86% and 72% of living participants respectively.
      Strategies addressing logistic, cultural and ethical challenges are documented.
      CONCLUSIONS: Satisfactory follow-up rates of a prospective longitudinal
      Indigenous birth cohort with traditional characteristics are possible while
      maintaining scientific rigor in a challenging setting. Approaches included
      flexibility, respect, and transparent communication along with the adoption of
      culturally sensitive behaviours. This work should inform and assist researchers
      undertaking or planning similar studies in Indigenous and developing populations.

PMID- 24568143
TI  - Gaps in Indigenous disadvantage not closing: a census cohort study of social
      determinants of health in Australia, Canada, and New Zealand from 1981-2006.
AB  - BACKGROUND: Australia, Canada, and New Zealand are all developed nations that are
      home to Indigenous populations which have historically faced poorer outcomes than
      their non-Indigenous counterparts on a range of health, social, and economic
      measures. The past several decades have seen major efforts made to close gaps in
      health and social determinants of health for Indigenous persons. We ask whether
      relative progress toward these goals has been achieved. METHODS: We used census
      data for each country to compare outcomes for the cohort aged 25-29 years at each
      census year 1981-2006 in the domains of education, employment, and income.
      RESULTS: The percentage-point gaps between Indigenous and non-Indigenous persons
      holding a bachelor degree or higher qualification ranged from 6.6% (New Zealand)
      to 10.9% (Canada) in 1981, and grew wider over the period to range from 19.5%
      (New Zealand) to 25.2% (Australia) in 2006. The unemployment rate gap ranged from
      5.4% (Canada) to 16.9% (Australia) in 1981, and fluctuated over the period to
      range from 6.6% (Canada) to 11.0% (Australia) in 2006. Median Indigenous income
      as a proportion of non-Indigenous median income (whereby parity = 100%) ranged
      from 77.2% (New Zealand) to 45.2% (Australia) in 1981, and improved slightly over
      the period to range from 80.9% (Canada) to 54.4% (Australia) in 2006.
      CONCLUSIONS: Australia, Canada, and New Zealand represent nations with some of
      the highest levels of human development in the world. Relative to their non
      Indigenous populations, their Indigenous populations were almost as disadvantaged
      in 2006 as they were in 1981 in the employment and income domains, and more
      disadvantaged in the education domain. New approaches for closing gaps in social
      determinants of health are required if progress on achieving equity is to
      improve.

PMID- 24568144
TI  - End of life in the intensive care unit: should French law be adapted?
AB  - BACKGROUND: Longstanding concerns regarding end of life in the ICU led in France
      to the publication of guidelines, updated in 2009, that take into account the
      insights provided by a recent law (Leonetti's law) regarding patients' rights.
      After the French President asked a specific expert to review end of life issues,
      the French Intensive Care Society (SRLF) surveyed their members (doctors and
      paramedics) about various aspects of end of life in the ICU. METHODS: SRLF
      members were invited to respond to a questionnaire, sent by Email, designed to
      assess their knowledge of Leonetti's law and to determine how many caregivers
      would agree with the authorization of lethal drug administration in selected end
      of life situations. RESULTS: Questionnaires returned by 616 (23%) of 2,700
      members were analyzed. Most members (82.5%) reported that they had a good
      knowledge of Leonetti's law, which most (88%) said they have often applied. One
      third of respondents had received 'assisted death' requests from patients and
      more than 50% from patients' relatives. One quarter of respondents had
      experienced the wish to give lethal drugs to end of life patients. Assuming that
      palliative care in the ICU is well-managed, 25.7% of the respondents would
      approve a law authorizing euthanasia, while 26.5% would not. Answers were
      influenced by the fear of a possible risk of abuse. Doctors and nurses answered
      differently. CONCLUSION: ICU caregivers appear to be well acquainted with
      Leonetti's law. Nevertheless, in selected clinical situations with suitable
      palliative care, one quarter of respondents were in favor of a law authorizing
      administration of lethal drugs to patients.

PMID- 24568145
TI  - Older adults' performance in technology-based tasks: cognitive ability and
      beyond.
AB  - Considering both demographic and technological changes in society, the potential
      of technology to support older adults has recently attracted much attention. For
      physically frail individuals with cognitive impairment, user-friendly
      technologies may facilitate activities of daily living. The current study
      assessed the performance of older adults without cognitive impairment (n = 27)
      and with mild cognitive impairment (n = 26) using three types of technology.
      Relationships between performance in the technology-based tasks and cognitive
      abilities (e.g., visual-spatial abilities), personality characteristics (e.g.,
      self-efficacy), and previous technology experience were examined using a mixed
      methods approach including video analyses and psychological testing. Findings
      underscore that both cognitive abilities and personality-related characteristics
      contribute to individual differences in users' performance. Nuanced knowledge of
      older adults' specific difficulties, abilities, and resources may help improve
      the fit between user needs and technological requirements, with implications for
      technology developers and practitioners.

PMID- 24568141
TI  - Genetic variation and recurrent parasitaemia in Peruvian Plasmodium vivax
      populations.
AB  - BACKGROUND: Plasmodium vivax is a predominant species of malaria in parts of
      South America and there is increasing resistance to drugs to treat infections by
      P. vivax. The existence of latent hypnozoites further complicates the ability to
      classify recurrent infections as treatment failures due to relapse, recrudescence
      of hyponozoites or re-infections. Antigen loci are putatively under natural
      selection and may not be an optimal molecular marker to define parasite
      haplotypes in paired samples. Putatively neutral microsatellite loci, however,
      offer an assessment of neutral haplotypes. The objective here was to assess the
      utility of neutral microsatellite loci to reconcile cases of recurrent
      parasitaemia in Amazonian P. vivax populations in Peru. METHODS: Patient blood
      samples were collected from three locations in or around Iquitos in the Peruvian
      Amazon. Five putatively neutral microsatellite loci were characterized from 445
      samples to ascertain the within and amongst population variation. A total of 30
      day 0 and day of recurrent parasitaemia samples were characterized at
      microsatellite loci and five polymorphic antigen loci for haplotype
      classification. RESULTS: The genetic diversity at microsatellite loci was
      consistent with neutral levels of variation measured in other South American P.
      vivax populations. Results between antigen and microsatellite loci for the 30 day
      0 and day of recurrent parasitaemia samples were the same for 80% of the pairs.
      The majority of non-concordant results were the result of differing alleles at
      microsatellite loci. This analysis estimates that 90% of the paired samples with
      the same microsatellite haplotype are unlikely to be due to a new infection.
      CONCLUSIONS: A population-level approach was used to yield a better estimate of
      the probability of a new infection versus relapse or recrudescence of homologous
      hypnozoites; hypnozoite activation was common for this cohort. Population studies
      are critical with the evaluation of genetic markers to assess P. vivax biology
      and epidemiology. The additional demonstration of microsatellite loci as neutral
      markers capable of distinguishing the origin of the recurrent parasites (new
      infection or originating from the patient) lends support to their use in
      assessment of treatment outcomes.

PMID- 24568146
TI  - The health of grandparents raising grandchildren: a literature review.
AB  - Around the world, an increasing number of grandparents are raising grandchildren
      in households without a biological parent. This is no less true in the United
      States, where grandparents raising grandchildren are at increased risk for
      depression and declining physical health. The purpose of this article is to
      explore the recent literature as it relates to the psychological and/or physical
      health of grandparents raising grandchildren. On reviewing 19 articles from the
      past 10 years, it is clear that the literature consistently verifies the health
      risks, especially depression, for grandparents raising grandchildren; however,
      the lack of research regarding grandfathers and non-African American caregivers
      is apparent. The factors influencing grandparents raising grandchildren are
      numerous, which calls for care providers to assess the needs, situations, and
      perceptions of grandparents individually. Finally, a need has arisen for more
      research suggesting and validating interventions that health care providers can
      use to support this population of older adults.

PMID- 24568148
TI  - Changes in performance over time while learning to use a myoelectric prosthesis.
AB  - BACKGROUND: Training increases the functional use of an upper limb prosthesis,
      but little is known about how people learn to use their prosthesis. The aim of
      this study was to describe the changes in performance with an upper limb
      myoelectric prosthesis during practice. The results provide a basis to develop an
      evidence-based training program. METHODS: Thirty-one able-bodied participants
      took part in an experiment as well as thirty-one age- and gender-matched
      controls. Participants in the experimental condition, randomly assigned to one of
      four groups, practiced with a myoelectric simulator for five sessions in a two
      weeks period. Group 1 practiced direct grasping, Group 2 practiced indirect
      grasping, Group 3 practiced fixating, and Group 4 practiced a combination of all
      three tasks. The Southampton Hand Assessment Procedure (SHAP) was assessed in a
      pretest, posttest, and two retention tests. Participants in the control condition
      performed SHAP two times, two weeks apart with no practice in between.
      Compressible objects were used in the grasping tasks. Changes in end-point
      kinematics, joint angles, and grip force control, the latter measured by
      magnitude of object compression, were examined. RESULTS: The experimental groups
      improved more on SHAP than the control group. Interestingly, the fixation group
      improved comparable to the other training groups on the SHAP. Improvement in
      global position of the prosthesis leveled off after three practice sessions,
      whereas learning to control grip force required more time. The indirect grasping
      group had the smallest object compression in the beginning and this did not
      change over time, whereas the direct grasping and the combination group had a
      decrease in compression over time. Moreover, the indirect grasping group had the
      smallest grasping time that did not vary over object rigidity, while for the
      other two groups the grasping time decreased with an increase in object rigidity.
      CONCLUSIONS: A training program should spend more time on learning fine control
      aspects of the prosthetic hand during rehabilitation. Moreover, training should
      start with the indirect grasping task that has the best performance, which is
      probably due to the higher amount of useful information available from the sound
      hand.

PMID- 24568149
TI  - Temporal dynamics of EEG activity during short- and long-wavelength light
      exposures in the early morning.
AB  - BACKGROUND: It is well known that exposure to light, especially of short
      wavelength, enhances human alertness during the nighttime. However, more
      information is needed to elucidate the effects of light wavelength on alertness
      at other times of day. The present study investigated how two narrowband light
      spectra affected human alertness during the morning after awakening. We measured
      electroencephalography (EEG) during 48-minute exposure to narrowband short- and
      long-wavelength light and darkness in the early morning. RESULTS: Power densities
      of EEG during each light exposure were calculated. The time course of EEG power
      indicated that, compared with remaining in darkness, the power in the alpha
      frequency range (8-13 Hz) was significantly lower after approximately 30 minutes
      of exposures to both the short- and the long-wavelength light. CONCLUSIONS: These
      results suggest that not only short-wavelength light but also long-wavelength
      light, which does not suppress melatonin levels at night, can affect alertness in
      the early morning. These results suggest that the alerting effects of light in
      the early morning hours may be mediated by mechanisms other than those that are
      exclusively sensitive to short-wavelength light.

PMID- 24568151
TI  - PtRu nanofilm formation by electrochemical atomic layer deposition (E-ALD).
AB  - The high CO tolerance of PtRu electrocatalysis, compared with pure Pt and other
      Pt-based alloys, makes it interesting as an anode material in proton exchange
      membrane fuel cells (PEMFC) and direct methanol fuel cells (DMFC). This report
      describes the formation of bimetallic PtRu nanofilms using the electrochemical
      form of atomic layer deposition (E-ALD). Metal nanofilm formation using E-ALD is
      facilitated by use of surface-limited redox replacement (SLRR), where an atomic
      layer (AL) of a sacrificial metal is first formed by UPD. The AL is then
      spontaneously exchanged for a more noble metal at the open-circuit potential
      (OCP). In the present study, PtRu nanofilms were formed using SLRR for Pt and Ru,
      and Pb UPD was used to form the sacrificial layers. The PtRu E-ALD cycle
      consisted of Pb UPD at -0.19 V, followed by replacement using Pt(IV) ions at OCP,
      rinsing with blank, then Pb UPD at -0.19 V, followed by replacement using Ru(III)
      ions at OCP. PtRu nanofilm thickness was controlled by the number of times the
      cycle was repeated. PtRu nanofilms with atomic proportions of 70/30, 82/18, and
      50/50 Pt/Ru were formed on Au on glass slides using related E-ALD cycles. The
      charge for Pb UPD and changes in the OCP during replacement were monitored during
      the deposition process. The PtRu films were then characterized by CO adsorption
      and electrooxidation to determine their overpotentials. The 50/50 PtRu nanofilms
      displayed the lowest CO electrooxidation overpotentials as well as the highest
      currents, compared with the other alloy compositions, pure Pt, and pure Ru. In
      addition, CO electrooxidation studies of the terminating AL on the 50/50 PtRu
      nanostructured alloy were investigated by deposition of one or two SLRR of Pt,
      Ru, or PtRu on top. 

PMID- 24568147
TI  - Clinical complications of G6PD deficiency in Latin American and Caribbean
      populations: systematic review and implications for malaria elimination
      programmes.
AB  - BACKGROUND: Although G6PDd individuals are generally asymptomatic throughout
      their life, the clinical burden of this genetic condition includes a range of
      haematological conditions, including acute haemolytic anaemia (AHA), neonatal
      jaundice (NNJ) and chronic non-sphaerocytic anaemia (CNSA). In Latin America
      (LA), the huge knowledge gap regarding G6PDd is related to the scarce
      understanding of the burden of clinical manifestation underlying G6PDd carriage.
      The aim of this work was to study the clinical significance of G6PDd in LA and
      the Caribbean region through a systematic review. METHODS: A systematic search of
      the published literature was undertaken in August 2013. Bibliographies of
      manuscripts were also searched and additional references were identified. Only
      original research was included. All study designs were included, as long as any
      clinical information was present. Studies were eligible for inclusion if they
      reported clinical information from populations living in LA or Caribbean
      countries or about migrants from these countries living in countries outside this
      continent. RESULTS: The Medline search generated 487 papers, and the LILACS
      search identified 140 papers. After applying the inclusion criteria, 100 original
      papers with any clinical information on G6PDd in LA were retrieved. Additionally,
      16 articles were included after reading the references from these papers. These
      116 articles reported data from 18 LA and Caribbean countries. The major clinical
      manifestations reported from LA countries were those related to AHA, namely drug
      induced haemolysis. Most of the published works regarding drug-induced haemolysis
      in LA referred to haemolytic crises in P. vivax malaria patients during the
      course of the treatment with primaquine (PQ). Favism, infection-induced
      haemolysis, NNJ and CNSA appear to play only a minor public health role in this
      continent. CONCLUSION: Haemolysis in patients using PQ seems to be the major
      clinical manifestation of G6PDd in LA and contributes to the morbidity of P.
      vivax infection in this continent, although the low number of reported cases,
      which could be linked to under-reporting of complications. These results support
      the need for better strategies to diagnose and manage G6PDd in malaria field
      conditions. Additionally, Malaria Control Programmes in LA should not overlook
      this condition in their national guidelines.

PMID- 24568150
TI  - Use of traditional medicines to cope with climate-sensitive diseases in a
      resource poor setting in Bangladesh.
AB  - BACKGROUND: This study aims to explore the use of traditional medicines to cope
      with climate sensitive diseases in areas vulnerable to climate change. We
      assessed the extent to which traditional or alternative medicines were used for
      the treatment of the climate sensitive diseases by villagers as part of their
      health-coping strategies. METHODS: The study deployed a mixed-method research
      design to know the health-coping strategies of the people in a resource-poor
      setting.A cross sectional study was conducted from September 2010 to March 2011
      among 450 households selected randomly in the districts of Rajshahi and Khulna,
      Bangladesh. The elder males or females of each household were interviewed. For
      qualitative methods, twelve focus group discussions (six with females and six
      with males) and fifteen key informant interviews were conducted by the research
      team, using interview guidelines on the use of traditional medicine. RESULTS:
      Univariate analysis showed that the use of traditional medicines has increased
      among community members of all socio-economic and demographic backgrounds. Due to
      the increased incidence of disease and sickness respondents had to increase the
      use of their cultural means to cope with adverse health situations. CONCLUSIONS:
      A systematic collection of knowledge on the use of traditional medicines to cope
      with climate-sensitive diseases can help the adaptation of communities vulnerable
      to climate change. In addition it can be instrumental in creating a directory of
      traditional medicine components used for specific diseases and highlight the
      effectiveness and relevance of traditional medicines as health-coping strategies.
      This may be useful for policymakers, researchers, and development partners to
      adapt existing health care policy in resource-limited contexts. It may also
      encourage WHO, national and international institutions, such as pharmaceutical
      companies, to carry out research investigating the effectiveness of these
      traditional medicines and integrate them with modern medicine. Overall, it could
      increase the health coping capacity of people in a resource-poor setting and
      contribute to their adaptation capabilities.

PMID- 24568152
TI  - Improved access and cycle time with an "in-house" patient-centered teleglaucoma
      program versus traditional in-person assessment.
AB  - BACKGROUND: To compare access time and cycle time between an "in-house"
      teleglaucoma program and in-person glaucoma consultation. PATIENTS AND METHODS:
      This was a prospective comparative study of 71 patients seen through the
      teleglaucoma program (eligible patients were glaucoma suspects or early-stage
      open-angle glaucoma) and 63 patients seen via a traditional in-person exam with a
      physician present. Access time was calculated as the time from the patient being
      referred to the date of a booked visit for either a teleglaucoma or in-person
      exam. Cycle time was defined as the time from registration until departure during
      the visit to the hospital; it was calculated for the subset of patients from each
      study group who completed activity logs on the day of their visit. RESULTS: The
      mean access time was significantly shorter for patients seen through teleglaucoma
      compared with in-person exam: 45+/-22 days (range, 13-121 days) (n=68) versus
      88+/-47 days (range, 27-214 days) (n=63), respectively (p<0.0001). The cycle time
      was also reduced for patients seen through teleglaucoma, compared with in-person
      assessment: 78+/-20 min (range, 40-130 min) (n=39) versus 115+/-44 min (range, 51
      216 min) (n=39), respectively (p<0.001). The mean percentage time spent in the
      waiting room was also significantly reduced for patients seen through
      teleglaucoma versus in-person assessments: 19+/-13% versus 41+/-24% (n=39),
      respectively (p<0.01). CONCLUSIONS: Teleglaucoma improves access to care and is a
      more efficient way of managing glaucoma suspects and patients with early-stage
      glaucoma compared with in-person assessment.

PMID- 24568153
TI  - Transactivation of EGFR by G protein-coupled receptor in the pathophysiology of
      intimal hyperplasia.
AB  - GPCR-mediated receptor transactivation of EGFR, is one of the effector mechanisms
      by which GPCR ligands, such as Ang II, thrombin and ET -1, catecholamine, SII
      angiotensin, PAF, and uPA that are released at the arterial injury sites, can
      potentiate intimal hyperplasia. The process of EGFR transactivation can be
      cognate ligand-dependent or independent. In cognate ligand- dependent
      transactivation, ligand-bound GPCR results in the activation of metalloproteases,
      which sheds membrane tethered growth factor that binds to EGFR on an
      extracellular ligand-binding domain causing its transactivation. Whereas, in
      cognate ligand independent transactivation, ligand bound GPCR activates EGFR
      intracellularly via second messenger system. The mechanism of EGFR
      transactivation depends on cell type, GPCR ligand and the type of GPCR. In this
      review article, such cross-talks are critically discussed. The EGFR
      transactivation generates mitogenic signals leading to various pathological
      conditions. The goal of this review article is to identify potential targets for
      therapeutic intervention in clinical conditions related to intimal hyperplasia in
      cardiovascular system. 

PMID- 24568154
TI  - Ca2+/calmodulin-dependent protein kinase- II in vasoactive peptide- induced
      responses and vascular biology.
AB  - Vasoactive peptides such as angiotensin II and endothelin-1 as well as growth
      factors regulate vascular homeostasis through signaling pathways that are
      triggered in both normal and disease states. These vasoactive peptides and growth
      factors also increase the cellular levels of calcium which, through calcium
      binding effector systems initiating the downstream signaling and physiological
      responses in target cells. A multifunctional calcium-calmodulin-dependent protein
      kinase II (CaMKII) has emerged as an important transducer of vasoactive peptide
      induced responses in vascular smooth muscle cells (VSMC). The catalytic activity
      of CaMKII can be stimulated by autophosphorylation and oxidation leading to the
      activation of signaling events that mediate growth, proliferation, migration, and
      gene transcription in VSMC. Pharmacological and gene deletion approaches have
      demonstrated a requirement of CaMKII in mediating the mitogen- activated protein
      kinase and phosphatidyl-inositol 3-kinase/protein kinase B signalling, as well as
      the proliferative, migratory and transcriptional responses of vasoactive
      peptides. In addition, a potential involvement of hyperactive CaMKII in animal
      models of vascular disease has also been reported. Therefore, this review aims to
      highlight the role of CaMKII in mediating signaling and physiological responses
      in VSMC and discuss its potential role in vascular pathophysiology. 

PMID- 24568155
TI  - Atypical G(alphai) signal transduction.
AB  - G protein signaling is an extremely complex event that is involved in almost
      every cellular process. As such, G protein-coupled receptors are the most
      commonly found type of transmembrane receptors used by cells to initiate
      intracellular signaling events. However, the widely accepted model of cyclical
      GDP-GTP exchange in response to ligand binding to 7TMRs, followed by dissociation
      of the G protein subunits and activation of intracellular signaling cascades, has
      repeatedly been challenged in recent years. Some of the exceptions that have been
      brought forth include signaling by a non-dissociated, rearranged heterotrimer and
      the existence of "reverse-mode", active G proteins that interact with active
      receptors. Here, we focus on G(alphai/o), one of the common G(alpha) classes, and
      outline a major exception to the classical model, that of G protein coupling to
      RTKs. We then describe a novel concept in G(alphai/o) signaling, namely that the
      pathways induced by agonist binding circumvent the typical signaling pathways
      responsive to decreases in the second messenger cAMP, via adenylyl cyclase
      inhibition.

PMID- 24568156
TI  - Endothelin-1 signaling in vascular physiology and pathophysiology.
AB  - The discovery of endothelin (ET) in 1988 has led to considerable effort to
      unravel its implication in health and disease and the mechanisms evoked by ET. ET
      1 and related signaling aberrancies are believed to be implicated in the
      pathogenesis of diverse cardiovascular diseases, such as hypertension,
      atherosclerosis, hypertrophy and diabetes. The endothelin system consists of
      three potent vasoconstrictive isopeptides, ET-1, ET-2 and ET-3, signaling through
      two G protein coupled receptors, ETA and ETB, which are linked to multiple
      signaling pathways. Activated signaling transduction pathways include the
      modulation of the adenylyl cyclase/cAMP pathway through stimulatory (Gs) and
      inhibitory (Gi) G proteins, activation of the phosphoinositide pathway through
      the activation of proteins Gq/11, generation of oxidative stress, growth factor
      receptor-related mitogenic events, such as the activation of phosphatidylinositol
      3 kinase pathway, phosphoinositide pathway and activation of the mitogen
      activated protein (MAP) kinase cascade. The levels of ETA and ETB receptors as
      well as the signaling pathways activated by these receptors are altered in
      several cardiovascular diseases including hypertension, hypertrophy,
      atherosclerosis, diabetes, etc. In this review, we provide an overview of the
      signaling events modulated by ET-1 in vascular smooth muscle cells in both
      physiological and pathological conditions. 

PMID- 24568157
TI  - Kinin receptors in vascular biology and pathology.
AB  - Endogenous kinins are important vasoactive peptides whose effects are mediated by
      two G-Protein-coupled receptors (R), named B2R (constitutive) and B1R
      (inducible). They are involved in vascular homeostasis, ischemic pre- and post-
      conditioning, but also in cardiovascular diseases. They contribute to the
      therapeutic effects of angiotensin-1 converting enzyme inhibitors (ACEI) and
      angiotensin AT1 receptor blockers. Benefits derive primarily from vasodilatory,
      antiproliferative, antihypertrophic, antifibrotic, antithrombic and antioxidant
      properties, which are associated with the release of endothelial factors such as
      nitric oxide, prostacyclin and tissue plasminogen activator. Uncontrolled
      production of kinins or the inhibition of their metabolism may lead to unwanted
      pro-inflammatory side effects. Thus, B2R antagonism is salutary in angioedema,
      septic shock, stroke, and Chagas vasculopathy. B1R is virtually absent in healthy
      tissues, yet this receptor is induced by the cytokine pathway and the oxidative
      stress via the transcriptional nuclear factor NF-kappaB. The B1R may play a
      compensatory role for the lack of B2R, and its up-regulation during tissue damage
      may be a useful mechanism of host defense. Activation of both receptors may be
      beneficial, notably in neovascularisation, angiogenesis, heart ischemia and
      diabetic nephropathy. At the same time, B1R is a potent activator of inducible
      nitric oxide and NADPH oxidase, which are associated with vascular inflammation,
      increased permeability, insulin resistance, endothelial dysfunction and diabetic
      complications. The dual beneficial and deleterious effects of kinin receptors
      and, particularly B1R, raise an unsettled issue on the therapeutic value of
      B1R/B2R agonists versus antagonists in cardiovascular diseases. Hence, the Janus
      face of kinin receptors needs to be seriously addressed in the upcoming clinical
      trials for each pathological setting. 

PMID- 24568158
TI  - Nuclear membranes GPCRs: implication in cardiovascular health and diseases.
AB  - G-protein coupled receptors (GPCRs) are commonly present at the plasma membrane
      and their signaling modulates excitation-contraction coupling and excitation
      secretion coupling of excitable and non-excitable cells of the cardiovascular
      system. Their effect on excitation-gene expression coupling was attributed, in
      part, to the nuclear translocation of their signaling and/or to the entry into
      the nuclear membrane of the internalized GPCRs. However, the recently established
      paradigm showed that, in addition to plasma membrane G-proteins, GPCRs exist as
      native nuclear membranes receptors and they modulate nuclear ionic homeostasis
      and function. These nuclear membrane GPCRs could function independently of plasma
      membrane GPCRs. Growing evidence also shows that these nuclear membrane GPCRs
      contribute to protein synthesis and also undergo changes in pathological
      conditions. The presence of a GPCR at both the plasma and nuclear membranes
      and/or only at the nuclear membranes represents a new challenge to better
      understand their contribution to cell physiology and pathology and, consequently,
      to the development of new therapeutic drugs targeting this category of receptors.

PMID- 24568159
TI  - Editorial: G-protein coupled receptors in vascular biology: implication in health
      and disease.

PMID- 24568160
TI  - Development of a natural-product-derived chemical toolbox for modulation of
      protein function.

PMID- 24568161
TI  - Betulinic acid as a potent and complex antitumor phytochemical: a minireview.
AB  - Betulinic acid (BA), a natural compound with a lupan skeleton, has been highly
      investigated in the past decade for a plethora of beneficial properties,
      including anti-cancer, anti-inflammatory, anti-angiogenic, immune-modulatory, and
      anti-HIV effects. In particular, BA has been reported to be effective in vitro
      against tumor cell lines of different origins, and also in vivo, in animal models
      of cancer. The best characterized mechanism of its antitumor effect consists of
      triggering apoptosis via the mitochondrial pathway. BA has also an anti
      metastatic effect via the prevention of the epithelial-to-mesencymal transition
      in highly aggressive melanoma cells. Furthermore, in the same model, BA is able
      to counteract the pro-invasive potential of the pro-tumoral protein neutrophil
      gelatinaseassociated lipocalin. The present review addresses the current state of
      knowledge regarding the anti-tumor effects of betulinic acid, a potent
      chemotherapeutic agent. 

PMID- 24568163
TI  - The indolylcoumarin COUFIN exhibits potent activity against renal carcinoma cells
      without affecting hematopoietic system.
AB  - The present work describes the anticancer activity of a new indolylcoumarin named
      COUFIN and more specifically, its efficiency against clear cell renal carcinoma
      (CCRC). COUFIN inhibited microtubule formation and bound on tubulin to or near
      the colchicine site. In vitro, COUFIN showed potent anticancer activity on renal
      carcinoma cells (RCC) both in monolayer (2D culture) (IC50 of 88 +/- 8 nM) and
      multicellular tumor spheroid (3D culture) (IC50 of 180 +/- 20 nM). The compound
      blocked cell cycle transition at G2/M phase, induced a subsequent apoptotic
      process but did not modulate clonal growth of CFU-GM. On the other hand, the
      coumarin derivative decreased the activity of P-gp and BCRP but was not substrate
      for these ABC pumps. In vivo, the indolylcoumarin increased the survival rate
      after 3 weeks of treatment. Based on the present study, COUFIN was identified as
      a bifunctional molecule able to inhibit renal carcinoma cells proliferation
      without being effluxed by ABC proteins. Thus COUFIN could be a promising
      chemotherapeutic agent for treating tumor cells over-expressing efflux pumps and
      tumor cells irrigated by vessels lined with endothelial cells responsible of poor
      distribution of conventional anticancer agents.

PMID- 24568162
TI  - Baicalin induces apoptosis of gallbladder carcinoma cells in vitro via a
      mitochondrial-mediated pathway and suppresses tumor growth in vivo.
AB  - Baicalin, the main active ingredient in the Scutellaria baicalensis (SB), is
      prescribed for the treatment of various inflammatory diseases and tumors in
      clinics in China. In the present study, we evaluated the antitumor activity of
      baicalin for gallbladder carcinoma and the underlying mechanisms both in vitro
      and in vivo. Our results indicate that baicalin induced potent growth inhibition,
      cell cycle arrest, apoptosis and colony-formation inhibition in a dose-dependent
      manner in vitro. We observed inhibition of NF-kappaB nuclear translocation, up
      regulation of Bax and down-regulation of Bcl-2, as well as increased caspase-3
      and caspase-9 expression after baicalin treatment in vitro and in vivo, which
      indicates that the mitochondrial pathway was involved in baicalin-induced
      apoptosis. In addition, daily intraperitoneally injection of baicalin (15, 30 and
      60 mg/kg) for 21 days significantly inhibited the growth of NOZ cells xenografts
      in nude mice, which improved the survival of baicalin-treated mice. In summary,
      baicalin exhibited a significant anti-tumor effect by suppressing cell
      proliferation, promoting apoptosis, and inducing cell cycle arrest in vitro, and
      by suppressing tumor growth and improving survival in vivo, which suggested that
      baicalin represents a novel therapeutic option for gallbladder carcinoma. 

PMID- 24568164
TI  - Presence of AmpC beta-lactamases, CSA-1, CSA-2, CMA-1, and CMA-2 conferring an
      unusual resistance phenotype in Cronobacter sakazakii and Cronobacter
      malonaticus.
AB  - Here we describe the presence of two very similar but unusual variants of AmpC
      cephalosporinase in each Cronobacter sakazakii and C. malonaticus isolates
      conferring resistance exclusively to first generation cephalosporins. During a
      survey on the antibiotic resistance patterns of C. sakazakii and C. malonaticus
      strains isolated from a milk powder production facility, originally two different
      phenotypes regarding the susceptibility/resistance for the two beta-lactam
      antibiotics ampicillin (amp) and cephalothin (ceph) were observed: (i) isolates
      being susceptible for both antibiotics (amp(S)/ceph(S)), and (ii) strains
      exhibiting susceptibility to ampicillin but resistance to cephalothin
      (amp(S)/ceph(R)). The latter phenotype (amp(S)/ceph(R)) was observed in the
      majority of the environmental strains from the facility. Analysis of whole genome
      sequences of C. sakazakii revealed a gene putatively coding for an AmpC beta
      lactamase. Consequently, the ampC genes from both species and both phenotypes
      were subjected to a cloning approach. Surprisingly, when expressed in Escherichia
      coli, all transformants exhibited the amp(S)/ceph(R) phenotype regardless of (i)
      the phenotypic backgrounds or (ii) the AmpC amino acid sequences of the original
      strains from which the clones were derived. The novel AmpC beta-lactamases were
      designated CSA-1 and CSA-2 (from C. sakazakii) and CMA-1 and CMA-2 (from C.
      malonaticus). The observed variations in the minimum inhibitory concentration
      (MIC) levels for cephalothin (wt compared to transformants) suggest that this
      feature is a target of a yet unknown regulatory mechanism present in the natural
      Cronobacter background but absent in the neutral E. coli host. 

PMID- 24568166
TI  - Facet cutting and hydrogenation of In(2)O(3) nanowires for enhanced
      photoelectrochemical water splitting.
AB  - Semiconductor nanowires (NWs) are useful building blocks in optoelectronic,
      sensing, and energy devices and one-dimensional NWs have been used in
      photoelectrochemical (PEC) water splitting because of the enhanced light
      absorption and charge transport. It has been theoretically predicted that the
      {001} facets of body center cubic (bcc) In2O3 nanocrystals can effectively
      accumulate photogenerated holes under illumination, but it is unclear whether
      facet cutting of NWs can enhance the efficiency of PEC water splitting. In this
      work, the photocurrent of square In2O3 NWs with four {001} facets is observed to
      be an order of magnitude larger than that of cylindrical In2O3 NWs under the same
      conditions and subsequent hydrogen treatment further promotes the PEC water
      splitting performance of the NWs. The optimized hydrogenated In2O3 NWs yield a
      photocurrent density of 1.2 mA/cm(2) at 0.22 V versus Ag/AgCl with a Faradaic
      efficiency of about 84.4%. The enhanced PEC properties can be attributed to the
      reduced band gap due to merging of the disordered layer-induced band tail states
      with the valence band as well as improved separation of the photogenerated
      electrons/holes between the In2O3 crystal core and disordered layer interface.
      The results provide experimental evidence of the important role of facet cutting,
      which is promising in the design and fabrication of NW-based photoelectric
      devices. 

PMID- 24568165
TI  - Short-term surgical and long-term survival outcomes after laparoscopic distal
      gastrectomy with D2 lymphadenectomy for gastric cancer.
AB  - BACKGROUND: Laparoscopic distal gastrectomy (LDG) for gastric cancer has
      gradually gained popularity. However, the long-term oncological outcomes of LDG
      have rarely been reported. This study aimed to investigate the survival outcomes
      of LDG, and evaluate the early surgical outcomes of laparoscopy-assisted distal
      gastrectomy (LADG) and totally laparoscopic distal gastrectomy (TLDG). METHODS:
      Clinical outcomes of 240 consecutive patients with gastric cancer who underwent
      LDG at our institution between October 2004 and April 2013 were analyzed. Early
      surgical outcomes of LADG and TLDG were compared and operative experiences were
      evaluated. RESULTS: Of the 240 patients, 93 underwent LADG and 147 underwent
      TLDG. There were 109 T1, 36 T2, 31 T3, and 64 T4a lesions. The median follow-up
      period was 31.5 months (range: 4-106 months). Tumor recurrence was observed in 40
      patients and peritoneal recurrence was observed most commonly. The 5-year disease
      free survival (DFS) and overall survival (OS) rates according to tumor stage were
      90.3% and 93.1% in stage I, 72.7% and 67.6% in stage II, and 34.8% and 41.5% in
      stage III, respectively. No significant differences in early surgical outcomes
      were noted such as operation time, blood loss and postoperative recovery between
      LADG and TLDG (P >0.05). CONCLUSIONS: LDG for gastric cancer had acceptable long
      term oncologic outcomes. The early surgical outcomes of the two commonly used LDG
      methods were similar.

PMID- 24568167
TI  - Unraveling the coupling between demixing and crystallization in mixtures.
AB  - Using molecular simulation, we shed light on the coupling between the two
      nonequilibrium processes of demixing and crystallization in mixtures of fully
      miscible, size-matched, liquid metals. We show that the competition between these
      processes has a strong impact on the crystallization pathway, leading to the
      formation of crystal nuclei with large excesses (up to 95%) in the component of
      higher cohesive energy, and resulting in increases of more than 30% in the free
      energy barrier of nucleation. The competition between demixing and
      crystallization goes on to impact the growth process, as shown by the large
      variations in composition observed at the surface and inside the growing
      crystallite. 

PMID- 24568168
TI  - Local structure and speciation of platinum in fresh and road-aged North American
      sourced vehicle emissions catalysts: an X-ray absorption spectroscopic study.
AB  - Given emerging concerns about the bioavailability and toxicity of anthropogenic
      platinum compounds emitted into the environment from sources including vehicle
      emission catalysts (VEC), the platinum species present in selected North American
      sourced fresh and road-aged VEC were determined by Pt and Cl X-ray absorption
      spectroscopy. Detailed analysis of the Extended X-ray Absorption Fine Structure
      at the Pt L3 and L2 edges of the solid phase catalysts revealed mainly oxidic
      species in the fresh catalysts and metallic components dominant in the road-aged
      catalysts. In addition, some bimetallic components (Pt-Ni, Pt-Pd, Pt-Rh) were
      observed in the road-aged catalysts from supporting Ni-, Pd-, and Rh-K edge XAS
      studies. These detailed analyses allow for the significant conclusion that this
      study did not find any evidence for the presence of chloroplatinate species in
      the investigated solid phase of a Three Way Catalyst or Diesel Oxidation
      Catalysts. 

PMID- 24568169
TI  - Comparison of the effect of two interdental cleaning devices around implants on
      the reduction of bleeding: a 30-day randomized clinical trial.
AB  - OBJECTIVE: To determine the effectiveness of a water flosser in reducing the
      bleeding on probing (BOP) index around dental implants as compared to flossing.
      METHODS AND MATERIALS: Patients with implants were randomly assigned to one of
      two groups in this examiner-masked, single-center study. The study compared the
      efficacy of a manual toothbrush paired with either traditional string floss or a
      water flosser. RESULTS: The primary outcome was the reduction in the incidence of
      BOP after 30 days. There were no differences in the percent of bleeding sites
      between the groups at baseline. At 30 days, 18 of the 22 (81.8%) implants in the
      water flosser group showed a reduction in BOP compared to 6 of the 18 (33.3%) in
      the floss group (P=0.0018). CONCLUSIONS: These results demonstrate that the water
      flosser group had statistically significantly greater bleeding reduction than the
      string floss group. The authors concluded that water flossing may be a useful
      adjuvant for implant hygiene maintenance.

PMID- 24568170
TI  - Physical properties and comparative strength of a bioactive luting cement.
AB  - New dental cement formulations require testing to determine physical and
      mechanical laboratory properties. OBJECTIVES: To test an experimental calcium
      aluminate/glass-ionomer cement, Ceramir C and B (CC and B), regarding compressive
      strength (CS), film thickness (FT), net setting time (ST) and Vickers hardness.
      An additional test to evaluate potential dimensional change/expansion properties
      of this cement was also conducted. METHODS AND MATERIALS: CS was measured
      according to a slightly modified ISO 9917:2003 for the CC and B specimens. The
      samples were not clamped while being exposed to relative humidity of great than
      90 percent at 37 degrees C for 10 minutes before being stored in phosphate
      buffered saline at 37 degrees C. For the CS, four groups were tested: Group 1-CC
      and B; Group 2-RelyX Luting Cement; Group 3-Fuji Plus; and Group 4-RelyX Unicem.
      Samples from all groups were stored for 24 hours before testing. Only CCandB was
      tested for ST and FT according to ISO 9917:2003. The FT was tested 2 minutes
      after mixing. Vickers hardness was evaluated using the CSM Microhardness
      Indentation Tester using zinc phosphate cement as a comparison material.
      Expansion testing included evaluating potential cracks in feldspathic porcelain
      jacket crowns (PJCs). RESULTS: The mean and standard deviation after 24 hours
      were expressed in MPa: Group 1 equals 160 plus or equal to 27; Group 2 equals 96
      plus or equal to 10; Group 3 equals 138 plus or equal to 15; Group 4 equals 157
      plus or equal to 10. A single-factor ANOVA demonstrated statistically significant
      differences between the groups (P less than 0.001). Pair-wise statistical
      comparison demonstrated a statistically significant difference between Groups 1
      and 2. No statistically significant differences were found between other groups.
      The FT was 16.8 plus or equal to 0.9 and the ST was 4.8 plus or equal to 0.1 min.
      Vickers hardness for Ceramir C and B was 68.3 plus or equal to 17.2 and was
      statistically significantly higher (P less than 0.05) than Fleck's Zinc Phosphate
      cement at Vickers hardness of 51.4 plus or equal to 10. There was no evidence of
      cracks due to radial expansion in PJCs by the Ceramir C and B cement. CONCLUSION:
      All luting cements tested demonstrated compressive strengths well in excess of
      the ISO requirement for water-based cements of no less than 50 MPa. Ceramir C and
      B showed significantly higher CS than RelyX Luting Cement after 24 hours, but was
      not significantly higher than either Fuji Plus or RelyX Unicem. The ST and FT
      values of CC and B conform to and are within the boundaries of the requirements
      of the standard. Surface hardness was statistically higher than and comparable to
      zinc phosphate cement. There was no evidence of potentially clinically
      significant and deleterious expansion behavior by this cement. All cements tested
      demonstrated acceptable strength properties. Within the limits of this study,
      Ceramir C and B is deemed to possess physical properties suitable for a dental
      luting cement.

PMID- 24568171
TI  - Comparative performance of two whitening systems in a dental practice.
AB  - OBJECTIVE: A randomized, controlled clinical trial was conducted to compare the
      safety and whitening efficacy of high-adhesion tooth-whitening strips with a
      marketed in-office professional tooth-whitening system. METHODS AND MATERIALS:
      This open-label study was conducted in a private dental practice, and adult
      volunteers were assigned (2:1) to either 9.5 percent hydrogen-peroxide whitening
      strips (Strip group) or an in-office light plus 25 percent hydrogen-peroxide
      whitening gel treatment (In-office group). The Strip group was instructed to
      treat the maxillary arch once daily for 30 minutes over a 20-day period, while
      the In-office group underwent professional application of light plus whitening
      gel in a single office visit. Whitening response was measured as change in
      yellowness (b*) and lightness (L*) at Day 21 using standardized digital images of
      the maxillary anterior teeth, while safety was assessed as tooth sensitivity and
      oral irritation occurrence. A total of 45 subjects enrolled, were randomized, and
      received treatment; 44 completed the study. RESULTS: At Day 21, significant
      improvement in b* and L* was noted in both groups (P<=0.001). The adjusted mean
      (SE) DeltaL* in the Strip group (1.72 (0.104)) was significantly greater than
      that in the In-office group (1.17 (0.153)) (P = 0.005). Both test products were
      well tolerated. Overall, both the strip and in-office treatments resulted in
      significant tooth whitening.

PMID- 24568172
TI  - Microleakage and microtensile bond strength of silorane-based and dimethacrylate
      based restorative systems.
AB  - OBJECTIVE: To evaluate the microleakage and bond strengths (microTBS) of silorane
      based (SBC) and dimethacrylate-based (DBC) restorative systems. The null
      hypotheses are: 1) there is no difference in microleakage between the resin
      composites and the adhesive systems tested at the enamel and dentin margins; 2)
      there is no significant difference in microTBS between the composite restorative
      systems using self-etch and etch-and-rinse adhesive versions. METHODS AND
      MATERIALS: Microleakage: Class V cavity preparations with cervical margin in
      dentin were performed on pristine extracted human molars and were randomly
      distributed among the following three groups: Group 1-DBC/etch-and-rinse adhesive
      system (FiltekTM Supreme Ultra/AdperTM Single Bond Plus, 3M ESPE,
      www.3MESPE.com); Group 2-SBC/self-etch adhesive (Filtek LS Low Shrink Posterior
      Restorative System/LS self-etch adhesive, 3M ESPE); Group 3-DBC/self-etch
      adhesive (Filtek Supreme Ultra/ Adper Easy Bond Self-Etch, 3M ESPE). Restorations
      were thermocycled and immersed in 0.2 percent methylene blue dye for 24 hours.
      Samples were assessed visually under 10x magnification; microTBS: Bond sticks
      (0.9 mm2) were prepared from each group and tested on a universal testing
      machine. RESULTS: The Kruskal-Wallis test revealed no significant difference in
      microleakage among the experimental groups at the enamel margin (P=0.191). At the
      dentin margins, silorane/self-etch restorative system showed significantly less
      leakage than the dimethacrylate/etch-and-rinse restorative system (P=0.008).
      Tukey's B rank order test showed that the dimethacrylate/etch-and-rinse
      restorative system presented the highest microTBS. CONCLUSIONS: SBC/self-etch
      system showed less microleakage at the dentin margins, while DBC/etch-and-rinse
      system presented higher bond strength.

PMID- 24568173
TI  - Interprofessional exemplars for health professional programmes at a South African
      university.
AB  - There are promising shifts towards transforming health professions education in
      South Africa, which include the development of interprofessional education
      undergraduate curricula. Interprofessional education was conceived as a means to
      improve quality of care by bringing together professions to learn and work in
      teams, thereby overcoming negative stereotypes and understanding and valuing the
      roles of the different health care professions. This paper aims to advance the
      agenda of transforming health professions education by showcasing the development
      of exemplars of interprofessional education offered in the Faculty of Community
      and Health Sciences at the University of the Western Cape in order to assist
      other higher education institutions in the process of developing
      interprofessional curricula. Each exemplar encompasses a range of interactive
      learning methods. Lessons learnt include the need for a common framework for
      interprofessional education; "buy in" and a mind-set change of academics and
      institutional structures to support and operationalize interprofessional
      education.

PMID- 24568174
TI  - One-step semisynthesis of oleacein and the determination as a 5-lipoxygenase
      inhibitor.
AB  - The dialdehydes oleacein (2) and oleocanthal (4) are closely related to
      oleuropein (1) and ligstroside (3), the two latter compounds being abundant
      iridoids of Olea europaea. By exploiting oleuropein isolated from the plant leaf
      extract, an efficient procedure has been developed for a one-step semisynthesis
      of oleacein under Krapcho decarbomethoxylation conditions. Highlighted is the
      fact that 5-lipoxygenase is a direct target for oleacein with an inhibitory
      potential (IC50: 2 MUM) more potent than oleocanthal (4) and oleuropein (1). This
      enzyme catalyzes the initial steps in the biosynthesis of pro-inflammatory
      leukotrienes. Taken together, the methodology presented here offers an
      alternative solution to isolation or total synthesis for the procurement of
      oleacein, thus facilitating the further development as a potential anti
      inflammatory agent. 

PMID- 24568175
TI  - Quantitative analysis of human ankle characteristics at different gait phases and
      speeds for utilizing in ankle-foot prosthetic design.
AB  - BACKGROUND: Ankle characteristics vary in terms of gait phase and speed change.
      This study aimed to quantify the components of ankle characteristics, including
      quasi-stiffness and work in different gait phases and at various speeds. METHODS:
      The kinetic and kinematic data of 20 healthy participants were collected during
      normal gait at four speeds. Stance moment-angle curves were divided into three
      sub-phases including controlled plantarflexion, controlled dorsiflexion and
      powered plantarflexion. The slope of the moment-angle curves was quantified as
      quasi-stiffness. The area under the curves was defined as work. RESULTS: The
      lowest quasi-stiffness was observed in the controlled plantarflexion. The fitted
      line to moment-angle curves showed R2 > 0.8 at controlled dorsiflexion and
      powered plantarflexion. Quasi-stiffness was significantly different at different
      speeds (P = 0.00). In the controlled dorsiflexion, the ankle absorbed energy; by
      comparison, energy was generated in the powered plantarflexion. A negative work
      value was recorded at slower speeds and a positive value was observed at faster
      speeds. Ankle peak powers were increased with walking speed (P = 0.00).
      CONCLUSIONS: Our findings suggested that the quasi-stiffness and work of the
      ankle joint can be regulated at different phases and speeds. These findings may
      be clinically applicable in the design and development of ankle prosthetic
      devices that can naturally replicate human walking at various gait speeds.

PMID- 24568176
TI  - Sensitive assay of protease activity on a micro/nanofluidics preconcentrator
      fused with the fluorescence resonance energy transfer detection technique.
AB  - A fast and sensitive assay of protease activity on a micro/nanofluidics
      preconcentrator combining with fluorescence resonance energy transfer (FRET)
      detection technique has been developed in a homogeneous real-time format. First,
      the functionalized nanoprobes are formed by loading dye labeled protein onto gold
      nanoparticles (AuNPs), in which, the photoluminescence of donor dye was strongly
      quenched by AuNPs due to FRET mechanisms. For protease activity assay, the
      nanoprobes are enriched by a micro/nanofluidics preconcentrator. When the target
      protease is transported to the enriched nanoprobes, cleavage of protein occurs as
      a consequence of molecular recognition of enzyme to substrate. The release of
      cleavage fragments from AuNPs nanoprobes leads to the enhancement of fluorescence
      and enables the protease activity assay on the micro/nanofluidics chip. As a
      demonstration, digestion of fluorescein isothiocyanate labeled dog serum albumin
      (FITC-DSA) by trypsin was used as a model reaction. Because of the highly
      efficient preconcentration and space confinement effect, significantly increased
      protein cleavage rate and protease assay sensitivity can be achieved with
      enhanced enzyme activity. The present micro/nanofluidics platform fused with the
      FRET detection technique is promising for fast and sensitive bioanalysis such as
      immunoassay, DNA hybridization, drug discovery, and clinical diagnosis. 

PMID- 24568178
TI  - "Giving voice": Evaluation of an integrated telehealth community care model by
      parents/guardians of children diagnosed with fetal alcohol spectrum disorder in
      Manitoba.
AB  - BACKGROUND: In 2000, Manitoba began utilizing telehealth services for the
      assessment, diagnosis and follow-up of fetal alcohol spectrum disorders (FASDs).
      Since that time, the use of telehealth in Manitoba has expanded to the delivery
      of education and support to families caring for children with FASD in rural and
      remote areas of the province. The purpose of this study was to expand on a
      previous evaluation through a focus on the participant experience. Our objectives
      were thus to explore the experience of families with the telehealth process and
      to examine the use of telehealth in diagnostic assessment as well as follow-up
      post-clinical assessment. MATERIALS AND METHODS: Sixteen semistructured
      interviews were conducted with families who had participated in at least one
      diagnostic assessment and/or individual or group follow-up via telehealth offered
      through the Manitoba FASD Centre. RESULTS: The majority of participants reported
      being happy with their experience(s) using telehealth for assessment, diagnosis,
      and/or follow-up support. Two general themes emerged from the data. The first
      theme is focused on the value of telehealth use for families with children living
      with FASD, whereas the second theme presents various needs of this client group.
      CONCLUSIONS: This study provides support for the use of telehealth as an
      effective technology beyond diagnosis for individuals with FASD and their
      families. Families support the utilization of this technology and, despite its
      minor shortcomings, appreciate the flexibility of telehealth, which allows them
      to remain in their home communities, connected to their families and support
      systems.

PMID- 24568177
TI  - The effect of ziprasidone on metabolic syndrome risk factors in subjects with
      schizophrenia: a 1 year, open-label, prospective study.
AB  - OBJECTIVE: Metabolic syndrome (MetS) is prevalent in subjects with schizophrenia
      related psychotic disorders and contributes to increased rates of premature death
      due to cardiovascular disease. This study examined the impact of switching from
      another antipsychotic to ziprasidone on the distribution of the number of risk
      factors for MetS in subjects with schizophrenia or related psychotic disorders.
      RESEARCH DESIGN AND METHODS: In this 1 year, open-label, prospective study, all
      subjects received ziprasidone 40-160 mg/day. Standard exclusion criteria included
      treatment resistance, physical health disorders, and substance abuse. The primary
      end point was the percentage of subjects achieving a reduction from baseline of
      at least one risk factor for MetS at end point (week 52 or premature
      discontinuation) in the per-protocol population (treated for at least 16 weeks).
      Secondary end points included the mean change from baseline in number of MetS
      risk factors, the prevalence of MetS, individual MetS risk factors (waist
      circumference, blood pressure, fasting triglycerides, high-density lipoprotein
      cholesterol, and glucose), and 10 year coronary heart disease (Framingham score)
      risk. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov: NCT00748566. MAIN
      OUTCOME MEASURES: Of 114 evaluable subjects, 58.77% demonstrated one less MetS
      risk factor at week 52 (last observation carried forward) compared with baseline.
      Secondary end points also improved, with reductions in other metabolic parameters
      (fasting low-density lipoprotein cholesterol, total cholesterol and serum
      insulin, weight, body mass index and glycosylated hemoglobin [HbA1c]). The 10
      year coronary heart disease risk decreased continually over time. The open-label
      and uncontrolled design is a limitation of the study. CONCLUSIONS: Ziprasidone
      treatment reduced both the rate of MetS and its individual risk factors in
      subjects with schizophrenia and related psychotic disorders. The results have
      implications for the selection of first-line treatments in schizophrenia and
      related psychotic disorders, and provide treatment options for subjects who have
      developed MetS as a result of other antipsychotics.

PMID- 24568179
TI  - Clinical observation on removal of small foreign bodies touching the optic nerve
      in the deep orbital region: a case series.
AB  - PURPOSE: Five patients presented to our institution with deep intraorbital
      foreign bodies adjacent to the optic nerve. We removed all foreign bodies by
      lateral orbitotomy to evaluate the treatment and the benefits of their
      extraction. METHODS: The clinical outcomes of the five patients were
      retrospectively analyzed. RESULTS: Radiology in all five patients revealed small
      foreign bodies touching the optic nerve in the deep orbital region. All patients
      also suffered from significant secondary psychological disturbances, these
      including anxiety and altered sleep patterns. They had become preoccupied with a
      strong desire to remove the intraorbital foreign bodies [IFB]. In this cohort,
      two had no light perception before surgery, another two had light perception, and
      one had hand motion perception as well as vitreous hemorrhage that had been
      plugged with silicone oil in other hospital. All foreign bodies were removed via
      lateral orbitotomy. Visual acuity improved after the operation in only three
      cases. However, the psychological well-being of all five patients improved.
      CONCLUSIONS: Consideration should be given to removal of intraorbital foreign
      bodies adjacent to the optic nerve, even where a significant degree of vision has
      already been lost. Furthermore some patients can achieved vision improvement and
      such surgery can frequently address the significant psychological disturbance
      that can be associated with such orbital foreign bodies.

PMID- 24568181
TI  - Asymmetric hydrogenation of olefins using chiral Crabtree-type catalysts: scope
      and limitations.

PMID- 24568180
TI  - Muscle motor point identification is essential for optimizing neuromuscular
      electrical stimulation use.
AB  - Transcutaneous neuromuscular electrical stimulation applied in clinical settings
      is currently characterized by a wide heterogeneity of stimulation protocols and
      modalities. Practitioners usually refer to anatomic charts (often provided with
      the user manuals of commercially available stimulators) for electrode
      positioning, which may lead to inconsistent outcomes, poor tolerance by the
      patients, and adverse reactions. Recent evidence has highlighted the crucial
      importance of stimulating over the muscle motor points to improve the
      effectiveness of neuromuscular electrical stimulation. Nevertheless, the correct
      electrophysiological definition of muscle motor point and its practical
      significance are not always fully comprehended by therapists and researchers in
      the field. The commentary describes a straightforward and quick
      electrophysiological procedure for muscle motor point identification. It consists
      in muscle surface mapping by using a stimulation pen-electrode and it is aimed at
      identifying the skin area above the muscle where the motor threshold is the
      lowest for a given electrical input, that is the skin area most responsive to
      electrical stimulation. After the motor point mapping procedure, a proper
      placement of the stimulation electrode(s) allows neuromuscular electrical
      stimulation to maximize the evoked tension, while minimizing the dose of the
      injected current and the level of discomfort. If routinely applied, we expect
      this procedure to improve both stimulation effectiveness and patient adherence to
      the treatment.The aims of this clinical commentary are to present an optimized
      procedure for the application of neuromuscular electrical stimulation and to
      highlight the clinical implications related to its use. 

PMID- 24568182
TI  - Subphthalocyanines, subporphyrazines, and subporphyrins: singular nonplanar
      aromatic systems.

PMID- 24568183
TI  - Asymptomatic intra-peritoneal rupture of hydatid cyst of the liver: case report.
AB  - BACKGROUND: Intra-peritoneal rupture of hydatid cyst is a rare complication and
      there is no consensus about its treatment. CASE PRESENTATION: The reported case
      concerns a 25 years old female patient who had been complaining for four months
      from a moderate pain in the right upper quadrant. No clinical or biological signs
      of sepsis or allergic reactions were witnessed. Ultrasound and CT examinations
      showed a multilocular hepatic cyst in addition to multiple unilocular cysts in
      the abdomen. The suspected diagnosis was hepatic and peritoneal HC and a surgical
      treatment was scheduled four weeks later. Surgical exploration showed a large
      ruptured HC on the left lobe of the liver, with daughter cysts in the peritoneal
      cavity. Left lobectomy of the liver with complete ablation of all daughter cysts
      and a wide peritoneal lavage were performed. For the three months following the
      surgery, Albendazole had been given to the patient. No recurrence occurred after
      four years of follow-up. CONCLUSION: Intra-peritoneal rupture of liver HC could
      be asymptomatic. This case showed that in some cases, occurrence of complications
      is not systematic. This suggests that urgent surgical treatment is not always
      mandatory in the absence of alarming signs. Well-conducted medical treatment
      would reduce the risk of occurrence of secondary peritoneal hydatidosis.

PMID- 24568184
TI  - Vaccination coverage and its determinants among migrant children in Guangdong,
      China.
AB  - BACKGROUND: Guangdong province attracted more than 31 million migrants in 2010.
      But few studies were performed to estimate the complete and age-appropriate
      immunization coverage and determine risk factors of migrant children. METHODS:
      1610 migrant children aged 12-59 months from 70 villages were interviewed in
      Guangdong. Demographic characteristics, primary caregiver's knowledge and
      attitude toward immunization, and child's immunization history were obtained. UTD
      and age-appropriate immunization rates for the following five vaccines and the
      overall series (1:3:3:3:1 immunization series) were assessed: one dose of BCG,
      three doses of DTP, OPV and HepB, one dose of MCV. Risk factors for not being UTD
      for the 1:3:3:3:1 immunization series were explored. RESULTS: For each antigen,
      the UTD immunization rate was above 71%, but the age-appropriate immunization
      rates for BCG, HepB, OPV, DPT and MCV were only 47.8%, 45.1%, 47.1%, 46.8% and
      37.2%, respectively. The 1st dose was most likely to be delayed within them. For
      the 1:3:3:3:1 immunization series, the UTD immunization rate and age-appropriate
      immunization rate were 64.9% and 12.4% respectively. Several factors as below
      were significantly associated with UTD immunization. The primary caregiver's
      determinants were their occupation, knowledge and attitude toward immunization.
      The child's determinants were sex, Hukou, birth place, residential buildings and
      family income. CONCLUSIONS: Alarmingly low immunization coverage of migrant
      children should be closely monitored by NIISS. Primary caregiver and child's
      determinants should be considered when taking measures. Strategies to strengthen
      active out-reach activities and health education for primary caregivers needed to
      be developed to improve their immunization coverage.

PMID- 24568186
TI  - 15-deoxy-Delta12,14-prostaglandin J2 induces p53 expression through Nrf2-mediated
      upregulation of heme oxygenase-1 in human breast cancer cells.
AB  - Heme oxygenase-1 (HO-1) is a stress-responsive enzyme that has antioxidant and
      cytoprotective functions. However, HO-1 has oncogenic functions in cancerous or
      transformed cells. In the present work, we investigated the effects of HO-1 on
      the expression of p53 induced by 15-deoxy-Delta(12,14)-prostaglandin J2 (15d
      PGJ2) in human breast cancer (MCF-7) cells. Treatment of MCF-7 cells with 15d
      PGJ2 led to time-dependent increases in the expression of p53 as well as HO-1.
      Upregulation of p53 expression by 15d-PGJ2 was abrogated by si-RNA knock-down of
      HO-1. In MCF-7 cells transfected with HO-1 si-RNA, 15d-PGJ2 failed to induce
      expression of p53 as well as HO-1. In addition, HO-1 inducers enhanced the p53
      expression. We speculated that iron, a by-product of HO-1-catalyzed reactions,
      could mediate 15d-PGJ2-induced p53 expression. Upregulation of p53 expression by
      15d-PGJ2 was abrogated by the iron chelator desferrioxamine in MCF-7 cells. Iron
      released from heme by HO-1 activity is mostly in the Fe(2+) form. When MCF-7
      cells were treated with the Fe(2+)-specific chelator phenanthroline, 15d-PGJ2
      induced p53 expression was attenuated. In addition, levels of the Fe-sequestering
      protein H-ferritin were elevated in 15d-PGJ2-treated MCF-7 cells. In conclusion,
      upregulation of p53 and p21 via HO-1 induction and subsequent release of iron
      with accumulation of H-ferritin may confer resistance to oxidative damage in
      cancer cells frequently challenged by redox-cycling anticancer drugs.

PMID- 24568187
TI  - Effects of mefepronic acid (2-phenoxy-2-methyl propionic acid) on hepatic
      metabolism and reproductive parameters in postpartum dairy cows.
AB  - This study investigates the effects of mefepronic acid (MA), a PPAR-alpha
      agonist, on hepatic metabolic functions and reproduction of postpartum dairy
      cows. Sixty Friesian cows were divided into Group A (administered 5g of MA IM,
      within 24 hrs after calving, on the 3(rd) and 5(th) day postpartum) and Group B
      (control). All the cows were blood sampled within 24 hrs of calving (Day 0), on
      Day 3, 5, 10, 15, 30, and 40 postpartum. On plasma, metabolic and biochemical
      parameters were determined. Liver biopsies were performed on Day 0, 15 and 30 for
      the evaluation of hepatic lipid and glycogen content. Reproductive parameters
      were also evaluated. In Group A, blood HDL, glucose and cholesterol increased
      till the end of the study, in accordance with the histological results. PPAR
      alpha immunopositive cells increased in liver slices of Group A, too.
      Reproductive parameters improved in Group A. This study highlights the beneficial
      effects of mefepronic acid on the hepatic metabolism and reproductive parameters
      of post-partum dairy cows. 

PMID- 24568185
TI  - wALADin benzimidazoles differentially modulate the function of porphobilinogen
      synthase orthologs.
AB  - The heme biosynthesis enzyme porphobilinogen synthase (PBGS) is a potential drug
      target in several human pathogens. wALADin1 benzimidazoles have emerged as
      species-selective PBGS inhibitors against Wolbachia endobacteria of filarial
      worms. In the present study, we have systematically tested wALADins against PBGS
      orthologs from bacteria, protozoa, metazoa, and plants to elucidate the
      inhibitory spectrum. However, the effect of wALADin1 on different PBGS orthologs
      was not limited to inhibition: several orthologs were stimulated by wALADin1;
      others remained unaffected. We demonstrate that wALADins allosterically modulate
      the PBGS homooligomeric equilibrium with inhibition mediated by favoring low
      activity oligomers, while 5-aminolevulinic acid, Mg(2+), or K(+) stabilized high
      activity oligomers. Pseudomonas aeruginosa PBGS could be inhibited or stimulated
      by wALADin1 depending on these factors and pH. We have defined the wALADin
      chemotypes responsible for either inhibition or stimulation, facilitating the
      design of tailored PBGS modulators for potential application as antimicrobial
      agents, herbicides, or drugs for porphyric disorders. 

PMID- 24568188
TI  - A cost-utility analysis of degarelix in the treatment of advanced hormone
      dependent prostate cancer in the United Kingdom.
AB  - OBJECTIVE: To determine the cost-effectiveness of the treatment of advanced
      hormone-dependent prostate cancer with degarelix compared to luteinizing hormone
      releasing hormone (LHRH) agonists in the UK using the latest available evidence
      and the model submitted to AWMSG. METHODS: A cost-effectiveness model was
      developed from the perspective of the UK National Health Service evaluating
      monthly injection of degarelix against 3-monthly leuprorelin therapy plus anti
      androgen flare cover for the first-line treatment of patients with advanced
      (locally advanced or metastatic) hormone-dependent prostate cancer. A Markov
      process model was constructed using the patient population characteristics and
      efficacy information from the CS21 Phase III clinical trial and associated
      extension study (CS21A). The intention-to-treat (ITT) population and a high-risk
      sub-group with a PSA level >20 ng/mL were modeled. RESULTS: In the base-case
      analysis using the patient access scheme (PAS) price, degarelix was dominant
      compared to leuprorelin with cost savings of L3633 in the ITT population and
      L4310 in the PSA > 20 ng/mL sub-group. The chance of being cost-effective was 95%
      in the ITT population and 96% in the PSA > 20 ng/mL sub-group at a threshold of
      L20,000 per quality-adjusted life-year (QALY). In addition, degarelix remained
      dominant when PSA progression was assumed equal and only the benefits of
      preventing testosterone flare were taken into account. Treatment with degarelix
      also remained dominant in both populations when the list price was used. The
      additional investment required to treat patients with degarelix could be offset
      in 19 months for the ITT population and 13 months for the PSA > 20 ng/mL
      population. The model was most sensitive to the hazard ratio assumed for PSA
      progression between degarelix and leuprorelin and the quality-of-life (utility)
      of patients receiving palliative care. CONCLUSION: Degarelix is likely to be cost
      effective compared to leuprorelin plus anti-androgen flare cover in the first
      line treatment of advanced hormone-dependent prostate cancer.

PMID- 24568190
TI  - In situ probing calcium carbonate formation by combining fast controlled
      precipitation method and small-angle X-ray scattering.
AB  - The initial stage of calcium carbonate nucleation and growth, found usually in
      "natural" precipitation conditions, is still not well understood. The calcium
      carbonate formation for moderate supersaturation level could be achieved by an
      original method called the fast controlled precipitation (FCP) method. FCP was
      coupled with SAXS (small-angle X-ray scattering) measurements to get insight into
      the nucleation and growth mechanisms of calcium carbonate particles in Ca(HCO3)2
      aqueous solutions. Two size distributions of particles were observed. The
      particle size evolutions of these two distributions were obtained by analyzing
      the SAXS data. A nice agreement was obtained between the total volume fractions
      of CaCO3 obtained by SAXS analysis and by pH-resistivity curve modeling (from FCP
      tests). 

PMID- 24568189
TI  - Antimicrobial resistance of bacterial enteropathogens isolated from stools in
      Madagascar.
AB  - BACKGROUND: Diarrheal diseases are a major public health problem in developing
      countries, and are one of the main causes of hospital admissions in Madagascar.
      The Pasteur Institute of Madagascar undertook a study to determine the prevalence
      and the pathogenicity of bacterial, viral and protozoal enteropathogens in
      diarrheal and non-diarrheal stools of children aged less than 5 years in
      Madagascar. We present here the results of the analysis of antimicrobial
      susceptibility of the bacteria isolated during this study. METHODS: The study was
      conducted in the community setting in 14 districts of Madagascar from October
      2008 to May 2009. Conventional methods and PCR were used to identify the
      bacteria; antimicrobial susceptibility was determined using an agar diffusion
      method for enterobacteriaceae and MICs were measured by an agar dilution method
      for Campylobacter sp. In addition to the strains isolated during this study,
      Salmonella sp and Shigella sp isolated at the Pasteur Institute of Madagascar
      from 2005 to 2009 were included in the analysis to increase the power of the
      study. RESULTS: Twenty-nine strains of Salmonella sp, 35 strains of Shigella sp,
      195 strains of diarrheagenic E. coli, 203 strains of C. jejuni and 71 strains of
      C. coli isolated in the community setting were tested for antibiotic resistance.
      Fifty-five strains of Salmonella sp and 129 strains of Shigella sp isolated from
      patients referred to the Pasteur Institute of Madagascar were also included in
      the study. Many E. coli and Shigella isolates (around 80%) but fewer Salmonella
      isolates were resistant to ampicillin and trimethoprim/sulfamethoxazole. A small
      proportion of strains of each species were resistant to ciprofloxacin and only 3%
      of E. coli strains presented a resistance to third generation cephalosporins due
      to the production of extended-spectrum beta-lactamases. The resistance of
      Campylobacter sp to ampicillin was the most prevalent, whereas less than 5% of
      isolates were resistant to each of the other antibiotics. CONCLUSION: The highest
      prevalence of antimicrobial resistance was to ampicillin and
      trimethoprim/sulfamethoxazole. Antibiotic treatment is not recommended for
      children with diarrhea in Madagascar and the emphasis should be placed on oral
      rehydration.

PMID- 24568191
TI  - Disease 'activity', 'severity' and 'impact': interrelationships in COPD; is a
      measure of disease 'activity' the Holy Grail for COPD, or a variable impossible
      to quantify?
AB  - It is increasingly recognised that new measures of disease 'activity' for COPD
      are required, however the relationship between markers of disease 'activity',
      'severity' and 'impact' though closely linked, is poorly understood.
      Additionally, while change in markers of disease 'severity' (e.g. change in FEV1)
      may be considered a marker of disease 'activity', these quantify a single aspect
      of disease 'activity' in COPD rather than measuring the overall disease process
      and this has stimulated the search for new biomarkers of COPD that reflect the
      'activity' of the disease process. The ideal biomarker of disease 'activity'
      would be stable with respect to time since measurement at any time point would
      then relate to subsequent disease progression. This would allow the influence of
      a therapeutic intervention to be assessed early, facilitating both phase 2 and 3
      clinical trials. Although a number of potential biomarkers of COPD disease
      'activity' have been studied, to date none have been shown to conclusively relate
      to disease progression and the stability of underlying disease 'activity'
      therefore requires further consideration. Interestingly, while the variability of
      disease 'activity' of COPD is rarely mentioned in the current literature, and
      there is uncertainty whether 'activity' is constant or highly variable, there are
      clues from available data as discussed in the current article. Finally we
      consider how markers of disease 'activity', 'severity' and 'impact' may relate,
      which is of utmost importance in the ongoing search for new biomarkers in COPD
      and a greater understanding of the pathogenesis of the disease process.

PMID- 24568193
TI  - Tuning of silver cluster emission from blue to red using a bio-active peptide in
      water.
AB  - Blue, green, and red emitting silver quantum clusters have been prepared through
      green chemical approach by using a bio-active peptide glutathione (reduced) in a
      50 mM phosphate buffer at pH 7.46. This study describes fluorescence emission
      tuning of the silver clusters by making different sized Ag clusters using
      slightly different reaction conditions keeping the same stabilizing ligand,
      reducing agent, solvent system, and silver salt precursor. The preparation
      procedure of these silver quantum clusters is new and highly reproducible. Each
      of these clusters shows very interesting fluorescence properties with large
      stokes shifts, and the quantum yields of blue, green, and red clusters are 2.08%,
      0.125%, and 1.39%, respectively. These silver quantum clusters have been
      characterized by using different techniques including fluorescence spectroscopy,
      UV-vis spectroscopy, field-emission gun transmission electron microscopic (FEG
      TEM) imaging and MALDI-TOF MS analyses. MALDI-TOF MS analyses show that the size
      of these blue, green and red emitting silver clusters are Ag5 (NC1, nanoclusters
      1), Ag8 (NC2, nanoclusters 2) and Ag13 (NC3, nanoclusters 3), respectively, by
      using 2,5-dihydroxybenzoic acid as a matrix. These clusters are stable in broad
      ranges of pH. The NC3 (red emitting) has been successfully utilized for selective
      and sensitive detection of toxic Hg(II) ions in water by using even naked eyes,
      fluorometric, and calorimetric studies. The lower limit of detection of Hg(II)
      ions in water has been estimated to be 126 and 245 nM from fluorometric and UV
      vis analyses, respectively. Enthalpy change (DeltaH) during this Hg(II) sensing
      process is 2508 KJ mol(-1). 

PMID- 24568196
TI  - Clusters encapsulated in endohedral metallofullerenes: how strained are they?
AB  - Endohedral clusters in metallofullerenes can vary in a broad range of geometrical
      parameters following the size and shape of the host carbon cage. Obviously,
      distortions of the cluster may increase its energy and even destabilize the whole
      clusterfullerene molecule. However, direct evaluation of the magnitude of cluster
      strain energies has not been done because of the lack of a suitable computational
      scheme that would allow one to decouple cluster and fullerene distortions and
      hence estimate individual components. In this work we offer a simple and
      efficient scheme to calculate cluster distortion energies in endohedral
      metallofullerenes (EMFs). Using this scheme, we analyze distortions in three
      classes of EMFs with nitride, sulfide, and carbide clusters and different metal
      atoms (Sc, Y, Ti). 

PMID- 24568192
TI  - cAMP signaling inhibits radiation-induced ATM phosphorylation leading to the
      augmentation of apoptosis in human lung cancer cells.
AB  - BACKGROUND: The ataxia-telangiectasia mutated (ATM) protein kinase plays a
      central role in coordinating the cellular response to radiation-induced DNA
      damage. cAMP signaling regulates various cellular responses including metabolism
      and gene expression. This study aimed to investigate the mechanism through which
      cAMP signaling regulates ATM activation and cellular responses to ionizing
      radiation in lung cancer cells. METHODS: Lung cancer cells were transfected with
      constitutively active stimulatory G protein (GalphasQL), and irradiated with
      gamma-rays. The phosphorylation of ATM and protein phosphatase 2A was analyzed by
      western blotting, and apoptosis was assessed by western blotting, flow cytometry,
      and TUNNEL staining. The promoter activity of NF-kappaB was determined by dual
      luciferase reporter assay. BALB/c mice were treated with forskolin to assess the
      effect in the lung tissue. RESULTS: Transient expression of GalphasQL
      significantly inhibited radiation-induced ATM phosphorylation in H1299 human lung
      cancer cells. Treatment with okadaic acid or knock down of PP2A B56delta subunit
      abolished the inhibitory effect of Galphas on radiation-induced ATM
      phosphorylation. Expression of GalphasQL increased phosphorylation of the
      B56delta and PP2A activity, and inhibition of PKA blocked Galphas-induced PP2A
      activation. GalphasQL enhanced radiation-induced cleavage of caspase-3 and PARP
      and increased the number of early apoptotic cells. The radiation-induced
      apoptosis was increased by inhibition of NF-kappaB using PDTC or inhibition of
      ATM using KU55933 or siRNA against ATM. Pretreatment of BALB/c mice with
      forskolin stimulated phosphorylation of PP2A B56delta, inhibited the activation
      of ATM and NF-kappaB, and augmented radiation-induced apoptosis in the lung
      tissue. GalphasQL expression decreased the nuclear levels of the p50 and p65
      subunits and NF-kappaB-dependent activity after gamma-ray irradiation in H1299
      cells. Pretreatment with prostaglandin E2 or isoproterenol increased B56delta
      phosphorylation, decreased radiation-induced ATM phosphorylation and increased
      apoptosis. CONCLUSIONS: cAMP signaling inhibits radiation-induced ATM activation
      by PKA-dependent activation of PP2A, and this signaling mechanism augments
      radiation-induced apoptosis by reducing ATM-dependent activation of NF-kappaB in
      lung cancer cells.

PMID- 24568197
TI  - Heparanase as a target in cancer therapy.
AB  - Heparanase is the unique and specific functional endoglycosidase capable of
      cleaving heparan sulfate (HS) chains. It exerts its enzymatic activity catalyzing
      the cleavage of the beta (1,4)-glycosidic bond between glucuronic acid and
      glucosamine residue. HS cleavage results in remodelling of the extracellular
      matrix as well as in regulating the release of many HS-linked molecules such as
      growth factors, cytokines and enzymes involved in inflammation, wound healing and
      tumour invasion. A pro-metastatic and pro-angiogenic role for this enzyme has
      been widely demonstrated in many primary human tumours since high levels of
      heparanase correlate with lymph node and distant metastasis, elevated micro
      vessel density and reduced survival of cancer patients. Recently, data have been
      reported that heparanase regulates heparan sulfate proteoglycan syndecan-1 and
      promotes its shedding from the cell surface. Shed syndecan-1 in turn controls
      tumour growth, metastasis and neo-angiogenesis mainly by promoting growth-factor
      signaling in the tumour milieu. Considering that, once inactivated, there are no
      other molecules capable of performing the same function, it is evident how this
      enzyme may be an effective and attractive drug target. Several heparanase
      inhibitors have been developed and some of them have undergone clinical trials
      showing efficacy against tumours. In this mini-review we will discuss current
      knowledge of heparanase involvement in cancer as well as its targeted inhibition
      as a promising therapeutic option in tumour treatment. 

PMID- 24568198
TI  - Silver nanoparticle behavior, uptake, and toxicity in Caenorhabditis elegans:
      effects of natural organic matter.
AB  - Significant progress has been made in understanding the toxicity of silver
      nanoparticles (Ag NPs) under carefully controlled laboratory conditions. Natural
      organic matter (NOM) is omnipresent in complex environmental systems, where it
      may alter the behavior of nanoparticles in these systems. We exposed the nematode
      Caenorhabditis elegans to Ag NP suspensions with or without one of two kinds of
      NOM, Suwannee River and Pony Lake fulvic acids (SRFA and PLFA, respectively).
      PLFA rescued toxicity more effectively than SRFA. Measurement of total tissue
      silver content indicated that PLFA reduced total organismal (including digestive
      tract) uptake of ionic silver, but not of citrate-coated Ag NPs (CIT-Ag NPs). The
      majority of the CIT-Ag NP uptake was in the digestive tract. Limited tissue
      uptake was detected by hyperspectral microscopy but not by transmission electron
      microscopy. Co-exposure to PLFA resulted in the formation of NOM-Ag NP composites
      (both in medium and in nematodes) and rescued AgNO3- and CIT-Ag NP-induced
      cellular damage, potentially by decreasing intracellular uptake of CIT-Ag NPs. 

PMID- 24568199
TI  - Chemo-somatosensory evoked potentials: a sensitive tool to assess conditioned
      pain modulation?
AB  - Abstract Background: Chemo-somatosensory evoked potentials (CSSEPs) elicited by
      chemical stimulation (CO2 gas) of the nasal mucosa have been shown to be
      sensitive enough to pick up even weak analgesic effects. With the present study
      we wanted to investigate whether CSSEPs are also a sensitive tool to capture
      endogenous pain inhibitory mechanisms elicited by conditioned pain modulation
      (CPM; where a first conditioning stimulus reduces the sensitivity for a second
      test stimulus) with a conditioning stimulus of rather low noxious load. METHODS:
      Seventeen healthy participants were tested for CPM effects (conditioning
      stimulus: tonic heat pain with intensities around the pain threshold induced via
      a thermode; test stimulus: chemonasal stimulation (73% and 78% CO2)) on CSSEPs
      and on self-report ratings. RESULTS: We found significant CPM effects in the
      CSSEPS, with reduced amplitudes and prolonged latencies at several
      electroencephalogram (EEG) recording positions when using the lower CO2
      concentration (73% CO2). In contrast to the visible inhibitory effects on the
      CSSEPs, subjective ratings of the test stimulus did not reflect CPM action.
      DISCUSSION: The experimental pain model using CO2 stimuli to elicit CSSEPs proved
      to be sensitive enough to capture weak CPM effects elicited by a conditioning
      stimulus of rather low noxious load. The usage of such mild noxious conditioning
      stimuli-in contrast to stimuli of higher noxious load (e.g., cold pressor test)
      has the advantage that the activation of other types of pain inhibitory
      mechanisms in parallel (like attentional distraction, stress-induced analgesia)
      can be avoided.

PMID- 24568200
TI  - High-affinity recombinant antibody fragments (Fabs) can be applied in peptide
      enrichment immuno-MRM assays.
AB  - High-affinity antibodies binding to linear peptides in solution are a
      prerequisite for performing immuno-MRM, an emerging technology for protein
      quantitation with high precision and specificity using peptide immunoaffinity
      enrichment coupled to stable isotope dilution and targeted mass spectrometry.
      Recombinant antibodies can be generated from appropriate libraries in high
      throughput in an automated laboratory and thus may offer advantages over
      conventional monoclonal antibodies. However, recombinant antibodies are typically
      obtained as fragments (Fab or scFv) expressed from E. coli, and it is not known
      whether these antibody formats are compatible with the established protocols and
      whether the affinities necessary for immunocapture of small linear peptides can
      be achieved with this technology. Hence, we performed a feasibility study to ask:
      (a) whether it is feasible to isolate high-affinity Fabs to small linear antigens
      and (b) whether it is feasible to incorporate antibody fragments into robust,
      quantitative immuno-MRM assays. We describe successful isolation of high-affinity
      Fab fragments against short (tryptic) peptides from a human combinatorial Fab
      library. We analytically characterize three immuno-MRM assays using recombinant
      Fabs, full-length IgGs constructed from these Fabs, or traditional monoclonals.
      We show that the antibody fragments show similar performance compared with
      traditional mouse- or rabbit-derived monoclonal antibodies. The data establish
      feasibility of isolating and incorporating high-affinity Fabs into peptide immuno
      MRM assays. 

PMID- 24568201
TI  - External validation of the CRASH and IMPACT prognostic models in severe traumatic
      brain injury.
AB  - An accurate prognostic model is extremely important in severe traumatic brain
      injury (TBI) for both patient management and research. Clinical prediction models
      must be validated both internally and externally before they are considered
      widely applicable. Our aim is to independently externally validate two prediction
      models, one developed by the Corticosteroid Randomization After Significant Head
      injury (CRASH) trial investigators, and the other from the International Mission
      for Prognosis and Analysis of Clinical Trials in Traumatic Brain Injury (IMPACT)
      group. We used a cohort of 300 patients with severe TBI (Glasgow Coma Score [GCS]
      <=8) consecutively admitted to the National Neuroscience Institute (NNI),
      Singapore, between February 2006 and December 2009. The CRASH models (base and
      CT) predict 14 day mortality and 6 month unfavorable outcome. The IMPACT models
      (core, extended, and laboratory) estimate 6 month mortality and unfavorable
      outcome. Validation was based on measures of discrimination and calibration.
      Discrimination was assessed using the area under the receiving operating
      characteristic curve (AUC), and calibration was assessed using the Hosmer
      Lemeshow (H-L) goodness-of-fit test and Cox calibration regression analysis. In
      the NNI database, the overall observed 14 day mortality was 47.7%, and the
      observed 6 month unfavorable outcome was 71.0%. The CRASH base model and all
      three IMPACT models gave an underestimate of the observed values in our cohort
      when used to predict outcome. Using the CRASH CT model, the predicted 14 day
      mortality of 46.6% approximated the observed outcome, whereas the predicted 6
      month unfavorable outcome was an overestimate at 74.8%. Overall, both the CRASH
      and IMPACT models showed good discrimination, with AUCs ranging from 0.80 to
      0.89, and good overall calibration. We conclude that both the CRASH and IMPACT
      models satisfactorily predicted outcome in our patients with severe TBI.

PMID- 24568202
TI  - 3-Aminobenzamide--a PARP inhibitor enhances the sensitivity of peripheral blood
      micronucleus and comet assays in mice.
AB  - CONTEXT: DNA repair is an essential outcome of DNA damage, which may compromise
      the end point of various in vitro and in vivo test systems of the genotoxicity
      evaluation. poly(ADP-ribose) polymerase (PARP) enzymes have an essential role in
      DNA repair. Here, we investigated the effect of 3-AB, a PARP inhibitor on the
      sensitivity of comet and PBMN assays. OBJECTIVE: This study aimed to enhance the
      sensitivity of the comet and peripheral blood micronucleus (PBMN) assays using 3
      aminobenzamide (3-AB), a well-characterized PARP inhibitor. MATERIALS AND
      METHODS: Cyclophosphamide (CP, 50 mg/kg), 5-flourouracil (5-FU, 25 mg/kg),
      zidovudine (AZT, 400 mg/kg) and furosemide (FUR, 60 mg/kg) were selected as
      genotoxins. 3-AB was given every 8 h with the first dose given 2 h before the
      genotoxin treatment. For the PBMN assay, small amount of blood was taken from the
      tail tip of each animal and smears were prepared. The comet assay was performed
      in PBL, bone marrow and liver. RESULTS: In the comet as well as PBMN assay, 3-AB
      pre-treatment enhanced the extent of DNA damage in all the combination groups (3
      AB + CP, 3-AB + 5-FU and 3-AB + AZT) compared to CP, 5-FU and AZT per se. 3-AB
      also enhanced the DNA damage caused by FUR in the bone marrow and liver.
      DISCUSSION: This study results clearly demonstrate that the pretreatment with 3
      AB (30 mg/kg) significantly enhances the sensitivity of the PBMN and comet
      assays. This model may be useful for the detection of marginally active DNA
      damaging agents.

PMID- 24568203
TI  - Tissue-specific attenuation of oncolytic sindbis virus without compromised
      genetic stability.
AB  - Wild-type Sindbis virus (SV) shows promise as an oncolytic agent, although
      potential off-target replication is a safety concern. To remove possible
      pathology reflecting virus replication in liver, muscle, and/or hematopoietic
      cells, microRNA (miR)-response elements (MREs) to liver-specific miR122, muscle
      specific miR133a and miR206, or hematopoietic-specific miR142-3p were inserted
      into the Sindbis viral genome. We compared the effectiveness of MREs in two
      distinct genomic locations and found better tissue-specific attenuation when they
      were inserted into the structural polyprotein coding region (up to 6000-fold
      selectivity with miR142-3p) rather than into the 3' untranslated region (up to
      850-fold with miR142-3p). While this degree of tissue-specific attenuation may be
      effective for relieving pathology in vivo, genetic instability of RNA viruses
      raises concerns over the mutation or loss of MREs conferring safety. Genetically
      modified SVs containing a reporter transgene, used as a surrogate for virus
      replication, mutated quickly in vitro, losing 50% transgene sequence within 6.2
      passages. Using a shorter insert containing MREs but no transgene, complete
      genetic stability was observed over at least 10 passages. We conclude that SV may
      be genetically modified to improve clinical properties, but attention must be
      paid to ensure that genetic stability is sufficient for intended applications.

PMID- 24568204
TI  - Propionibacterium acnes prosthetic valve endocarditis with abscess formation: a
      case report.
AB  - BACKGROUND: Endocarditis due to Propionibacterium acnes is a rare disease. Scant
      data on treatment of these infections is available and is based on case reports
      only. If the disease is complicated by abscess formation, surgical intervention
      combined with an antibiotic therapy might improve clinical outcome. In some
      cases, cardiac surgeons are reluctant to perform surgery, since they consider the
      intervention as high risk. Therefore, a conservative therapy is required, with
      little, if any evidence to choose the optimal antibiotic. We report the first
      case of a successfully treated patient with P. acnes prosthetic valve
      endocarditis without surgery. CASE PRESENTATION: We report the case of a 29-year
      old patient with a prosthetic valve endocarditis and composite graft infection
      with abscess formation of the left ventricular outflow tract due to P. acnes.
      Since cardiac surgery was considered as high risk, the patient was treated
      intravenously with ceftriaxone 2 g qd and rifampin 600 mg bid for 7 weeks and was
      switched to an oral therapy with levofloxacin 500 mg bid and rifampin 600 mg bid
      for an additional 6 months. Two sets of blood cultures collected six weeks after
      completion of treatment remained negative. The patient is considered to be cured
      based on absence of clinical signs and symptoms, normal laboratory parameters,
      negative radiology scans and negative blood cultures, determined at site visits
      over two years after completion of treatment. CONCLUSION: To our knowledge, this
      is the first successfully managed patient with P. acnes prosthetic valve
      endocarditis with abscess formation of the left ventricular outflow tract who was
      treated with antibiotics alone without a surgical intervention. A six month
      treatment with a rifampin and levofloxacin combination was chosen, based on the
      excellent activity against stationary-phase and adherent bacteria.

PMID- 24568205
TI  - Exploring the roles of spectral detail and intonation contour in speech
      intelligibility: an FMRI study.
AB  - The melodic contour of speech forms an important perceptual aspect of tonal and
      nontonal languages and an important limiting factor on the intelligibility of
      speech heard through a cochlear implant. Previous work exploring the neural
      correlates of speech comprehension identified a left-dominant pathway in the
      temporal lobes supporting the extraction of an intelligible linguistic message,
      whereas the right anterior temporal lobe showed an overall preference for signals
      clearly conveying dynamic pitch information [Johnsrude, I. S., Penhune, V. B., &
      Zatorre, R. J. Functional specificity in the right human auditory cortex for
      perceiving pitch direction. Brain, 123, 155-163, 2000; Scott, S. K., Blank, C.
      C., Rosen, S., & Wise, R. J. Identification of a pathway for intelligible speech
      in the left temporal lobe. Brain, 123, 2400-2406, 2000]. The current study
      combined modulations of overall intelligibility (through vocoding and spectral
      inversion) with a manipulation of pitch contour (normal vs. falling) to
      investigate the processing of spoken sentences in functional MRI. Our overall
      findings replicate and extend those of Scott et al. [Scott, S. K., Blank, C. C.,
      Rosen, S., & Wise, R. J. Identification of a pathway for intelligible speech in
      the left temporal lobe. Brain, 123, 2400-2406, 2000], where greater sentence
      intelligibility was predominately associated with increased activity in the left
      STS, and the greatest response to normal sentence melody was found in right
      superior temporal gyrus. These data suggest a spatial distinction between brain
      areas associated with intelligibility and those involved in the processing of
      dynamic pitch information in speech. By including a set of complexity-matched
      unintelligible conditions created by spectral inversion, this is additionally the
      first study reporting a fully factorial exploration of spectrotemporal complexity
      and spectral inversion as they relate to the neural processing of speech
      intelligibility. Perhaps surprisingly, there was little evidence for an
      interaction between the two factors-we discuss the implications for the
      processing of sound and speech in the dorsolateral temporal lobes. 

PMID- 24568206
TI  - The epidemiology of polyparasitism and implications for morbidity in two rural
      communities of Cote d'Ivoire.
AB  - BACKGROUND: Polyparasitism is still widespread in rural communities of the
      developing world. However, the epidemiology of polyparasitism and implications
      for morbidity are poorly understood. We studied patterns of multiple species
      parasite infection in two rural communities of Cote d'Ivoire, including
      associations and interactions between infection, clinical indicators and self
      reported morbidity. METHODS: Between August and September 2011, two purposely
      selected rural communities in southern Cote d'Ivoire were screened for helminth,
      intestinal protozoa and Plasmodium infection, using a suite of quality-controlled
      diagnostic methods. Additionally, participants were examined clinically and we
      measured haemoglobin level, height, weight and mid-upper arm circumference to
      determine nutritional status. An anamnestic questionnaire was administered to
      assess people's recent history of diseases and symptoms, while a household
      questionnaire was administered to heads of household to collect socioeconomic
      data. Multivariate logistic regression models were applied for assessment of
      possible associations between parasitic (co-)infections and morbidity outcomes.
      RESULTS: 912/1,095 (83.3%) study participants had complete parasitological data
      and 852 individuals were considered for in-depth analysis. The rate of
      polyparasitism was high, with Plasmodium falciparum diagnosed as the predominant
      species, followed by Schistosoma haematobium, Schistosoma mansoni and hookworm.
      There were considerable differences in polyparasitic infection profiles among the
      two settings. Clinical morbidity such as anaemia, splenomegaly and malnutrition
      was mainly found in young age groups, while in adults, self-reported morbidity
      dominated. High parasitaemia of P. falciparum was significantly associated with
      several clinical manifestations such as anaemia, splenomegaly and fever, while
      light-intensity helminth infections seemed to have beneficial effects,
      particularly for co-infected individuals. CONCLUSIONS: Clinical morbidity is
      disturbingly high in young age groups in rural communities of Cote d'Ivoire and
      mainly related to very high P. falciparum endemicity. Interactions between
      helminth infections and P. falciparum burden (parasitaemia and clinical
      morbidity) are evident and must be taken into account to design future
      interventions.

PMID- 24568207
TI  - Genetic characterization of type 2a canine parvoviruses from Taiwan reveals the
      emergence of an Ile324 mutation in VP2.
AB  - BACKGROUND: Canine parvovirus 2 (CPV 2) is a major infectious cause of mortality
      in puppies. The characteristic symptom of CPV 2 disease is intestinal hemorrhage
      with severe bloody diarrhea. Soon after CPV was first recognized in the late
      1970s, the original virus, CPV 2, was replaced in the canine population by
      strains carrying minor antigenic variants (termed 2a, 2b, and 2c) of the VP2 gene
      that could be distinguished using monoclonal antibodies and molecular analyses.
      Here, we provide an updated molecular characterization of the CPV 2 circulating
      in Taiwan. METHODS: In this study, 28 isolates of CPV 2 from 144 dogs with
      suspected CPV infection were obtained from northern, central, and southern Taiwan
      from 2008 to 2012 and screened by PCR. The 28 isolates were sequenced, and a
      phylogenetic analysis of the VP2 gene was performed. RESULTS: Of the 28 Taiwanese
      CPV 2 isolates, 15 were identified as new CPV 2a, and 13 were identified as new
      CPV 2b. Compared to the reference CPV 2a, all 15 of the CPV 2a sequences
      collected in this study contain an Ile324 mutation caused by a TAT to ATT
      mutation at nucleotides 970-972 of the VP2 gene. CONCLUSION: Our VP2 sequence
      data revealed that both types are currently prevalent CPV 2 field strains
      circulating in Taiwan, and a unique Ile324 VP2 mutation was found in our
      Taiwanese CPV 2a isolates and recent Asian isolates. CPV 2c was not observed in
      this study.

PMID- 24568209
TI  - The effect of chair yoga in older adults with moderate and severe Alzheimer's
      disease.
AB  - Using a quasi-experimental single-group design, this study examined the
      feasibility of older adults with Alzheimer's disease (AD)-type dementia to
      complete the Sit 'N' Fit Chair Yoga Program. Physical function of participants
      who completed the program was measured. The nine older adults with AD (mean age =
      83) participated in the 8-week Sit 'N' Fit Chair Yoga Program. To measure
      physical function, the Six-Minute Walk Test, the Gait Speed Test, and the Berg
      Balance Scale were administered at pre-intervention, 4 weeks, 8 weeks, and 1
      month after program completion. All participants completed the program. Positive
      changes were seen across all physical measures. Further study, using a larger
      sample and including a control group, is needed to fully determine the effect of
      the Sit 'N' Fit Chair Yoga Program on older adults with moderate to severe AD.

PMID- 24568210
TI  - Simultaneous isolated bilateral superior orbital vein thrombosis as a presenting
      feature of antiphospholipid syndrome.
AB  - PURPOSE: To report a rare case of isolated bilateral simultaneous superior
      ophthalmic vein occlusions secondary to antiphospholipid syndrome. CASE REPORT:
      We report the case of a 77-year-old female who presented with a one week history
      of right relative proptosis, conjunctival injection and optic disc swelling.
      Magnetic resonance imaging revealed bilateral orbital masses which were diagnosed
      as superior ophthalmic vein occlusion. The patient was anticoagulated and the
      lesions resolved completely. System cardiovascular and haematological work-up
      revealed the patient was suffering from anti-phospholipid syndrome. CONCLUSION:
      Although superior ophthalmic vein occlusion is rare, it is an important
      differential as orbital biopsy is to be avoided. This is only the second reported
      case secondary to antiphospholipid syndrome and the first such case with
      bilateral occlusions.

PMID- 24568208
TI  - Occupational risk factors for COPD phenotypes in the Multi-Ethnic Study of
      Atherosclerosis (MESA) Lung Study.
AB  - INTRODUCTION: The contribution of occupational exposure to the risk of chronic
      obstructive pulmonary disease COPD in population-based studies is of interest. We
      compared the performance of self-reported exposure to a newly developed JEM in
      exposure-response evaluation. METHODS: We used cross-sectional data from Multi
      Ethnic Study of Atherosclerosis (MESA), a population-based sample of 45-84 year
      olds free of clinical cardiovascular disease at baseline. MESA ascertained the
      most recent job and employment, and the MESA Lung Study measured spirometry, and
      occupational exposures for 3686 participants. Associations between health
      outcomes (spirometry defined airflow limitation and Medical Research Council
      defined chronic bronchitis) and occupational exposure [self-reported occupational
      exposure to vapor-gas, dust, or fumes (VGDF), severity of exposure, and a job
      exposure matrix (JEM)-derived score] were evaluated using logistic regression
      models adjusted for non-occupational risk factors. RESULTS: The prevalence of
      airflow limitation was associated with self-reported exposure to vapor-gas (OR
      2.6, 95%CI 1.1-2.3), severity of VGDF exposure (P-trend < 0.01), and JEM dust
      exposure (OR 2.4, 95%CI 1.1-5.0), and with organic dust exposure in females;
      these associations were generally of greater magnitude among never smokers. The
      prevalence of chronic bronchitis and wheeze was associated with exposure to VGDF.
      The association between airflow limitation and the combined effect of smoking and
      VGDF exposure showed an increasing trend. Self-reported vapor-gas, dust, fumes,
      years and severity of exposure were associated with increased prevalence of
      chronic bronchitis and wheeze (P < 0.001). CONCLUSIONS: Airflow limitation was
      associated with self-reported VGDF exposure, its severity, and JEM-ascertained
      dust exposure in smokers and never-smokers in this multiethnic study.

PMID- 24568212
TI  - Magnetically recoverable, thermostable, hydrophobic DNA/silica encapsulates and
      their application as invisible oil tags.
AB  - A method to encapsulate DNA in heat-resistant and inert magnetic particles was
      developed. An inexpensive synthesis technique based on co-precipitation was
      utilized to produce Fe2O3 nanoparticles, which were further functionalized with
      ammonium groups. DNA was adsorbed on this magnetic support, and the DNA/magnet
      nanocluster was surface coated with a dense silica layer by sol-gel chemistry.
      The materials were further surface modified with hexyltrimethoxysilane to achieve
      particle dispersibility in hydrophobic liquids. The hydrodynamic particle sizes
      were evaluated by analytical disc centrifugation, and the magnetic properties
      were investigated by vibrating sample magnetometry. The obtained nanoengineered
      encapsulates showed good dispersion abilities in various nonaqueous fluids and
      did not affect the optical properties of the hydrophobic dispersant when present
      at concentrations lower than 10(3) MUg/L. Upon magnetic separation and particle
      dissolution, the DNA could be recovered unharmed and was analyzed by quantitative
      real-time PCR and Sanger sequencing. DNA encapsulated within the magnetic
      particles was stable for 2 years in decalin at room temperature, and the
      stability was further tested at elevated temperatures. The new magnetic
      DNA/silica encapsulates were utilized to developed a low-cost platform for the
      tracing/tagging of oils and oil-derived products, requiring 1 MUg/L=1 ppb levels
      of the taggant and allowing quantification of taggant concentration on a
      logarithmic scale. The procedure was tested for the barcoding of a fuel
      (gasoline), a cosmetic oil (bergamot oil), and a food grade oil (extra virgin
      olive oil), being able to verify the authenticity of the products.

PMID- 24568213
TI  - A hybrid macrocycle with a pyridine subunit displays aromatic character upon
      uranyl cation complexation.
AB  - Reported here is a new hybrid macrocycle, cyclo[1]furan[1]pyridine[4]pyrrole (1),
      that bears analogy to the previously reported mixed heterocycle system
      cyclo[2]pyridine[4]pyrrole (2) and cyclo[6]pyrrole 3, an all-pyrrole 22 pi
      electron aromatic expanded porphyrin. The oxidized, dianionic form of 1, [1 -
      4H](2-), has been characterized as its uranyl complex. In contrast to 2 and 3 and
      in spite of the presence of a 2,6-disubstituted pyridine subunit, the uranyl
      complex of [1 - 4H](2-) displays solid-state structural and solution-phase
      spectroscopic features consistent with contributions to the overall electronic
      structure that involve a conjugated, (4n + 2) pi-electron aromatic periphery. 

PMID- 24568214
TI  - Simple and reliable method to incorporate the Janus property onto arbitrary
      porous substrates.
AB  - Economical fabrication of waterproof/breathable substrates has many potential
      applications such as clothing or improved medical dressing. In this work, a
      facile and reproducible fabrication method was developed to render the Janus
      property to arbitrary porous substrates. First, a hydrophobic surface was
      obtained by depositing a fluoropolymer, poly(3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10
      heptadecafluorodecyl methacrylate) (PHFDMA), on various porous substrates such as
      polyester fabric, nylon mesh, and filter paper. With a one-step vapor-phase
      deposition process, termed as initiated chemical vapor deposition (iCVD), a
      conformal coating of hydrophobic PHFDMA polymer film was achieved on both faces
      of the porous substrate. Since the hydrophobic perfluoroalkyl functionality is
      tethered on PHFDMA via hydrolyzable ester functionality, the hydrophobic
      functionality on PHFDMA was readily released by hydrolysis reaction. Here, by
      simply floating the PHFDMA-coated substrates on KOH(aq) solution, only the face
      of the PHFDMA-coated substrate in contact with the KOH(aq) solution became
      hydrophilic by the conversion of the fluoroalkyl ester group in the PHFDMA to
      hydrophilic carboxylic acid functionality. The hydrophilized face was able to
      easily absorb water, showing a contact angle of less than 37 degrees . However,
      the top side of the PHFDMA-coated substrate was unaffected by the exposure to
      KOH(aq) solution and remained hydrophobic. Moreover, the carboxylated surface was
      further functionalized with aminated polystyrene beads. The porous Janus
      substrates fabricated using this method can be applied to various kinds of
      clothing such as pants and shirts, something that the lamination process for Gore
      tex has not allowed. 

PMID- 24568215
TI  - Clostridia initiate heavy metal bioremoval in mixed sulfidogenic cultures.
AB  - Sulfate reducing bacteria (SRB) are widely used for attenuating heavy metal
      pollution by means of sulfide generation. Due to their low metal tolerance,
      several SRB species depend on associated bacteria in mixed cultures to cope with
      metal-induced stress. Yet the identity of the SRB protecting bacteria is largely
      unknown. We aimed to identify these associated bacteria and their potential role
      in two highly metal-resistant mixed SRB cultures by comparing bacterial community
      composition and SRB activity between these cultures and two sensitive ones. The
      SRB composition in the resistant and sensitive consortia was similar. However,
      whereas the SRB in the sensitive cultures were strongly inhibited by a mixture of
      copper, zinc, and iron, no influence of these metals was detected on SRB growth
      and activity in the resistant cultures. In the latter, a Gram-positive population
      mostly assigned to Clostridium spp. initiated heavy metal bioremoval based on
      sulfide generation from components of the medium (mainly sulfite) but not from
      sulfate. After metal levels were lowered by the Clostridium spp. populations, SRB
      started sulfate reduction and raised the pH of the medium. The combination of
      sulfite reducing Clostridium spp. with SRB may improve green technologies for
      removal of heavy metals. 

PMID- 24568216
TI  - Smile transformations with the use of direct composite restorations.
AB  - Mutual concerns shared by dentists and patients regarding removal of natural
      tooth structure affirm the need for non-invasive restorative treatments. Direct
      composite restorations are among today's conservative treatment modalities.
      Direct bonding procedures provide patients with an alternative to high biologic
      risk and expensive indirect porcelain restorations. This article discusses the
      principles involved in smile design cases, ways to successfully combine different
      treatment modalities, and materials to achieve outstanding esthetic and
      functional results. The article also demonstrates the versatility of today's
      composite materials for direct smile design restorations. 

PMID- 24568217
TI  - Predictable nanohybrid composite systems and techniques for anterior and
      posterior direct restorations.
AB  - Advancements in the chemical composition of direct restorative materials have
      facilitated greater ease of use, better handling, and enhanced functional
      predictability. Nanohybrid composites are among these innovations, providing
      enhanced physical and optical properties that contribute to easier and long
      lasting polishability, enhanced shade matching and light reflection/deflection
      properties, and reduced shrinkage. Becoming familiar with a particular composite
      system and following a repeatable protocol for routine restorations are key to
      achieving predictable and long-lasting restorative results. This article reviews
      the advantageous characteristics of nanohybrid composites and demonstrates the
      use of two complementary composite systems for anterior and posterior
      restorations. 

PMID- 24568218
TI  - Establishing gingival symmetry when placing anterior direct nanohybrid composite
      restorations.
AB  - Restoring the beauty of patients' smiles requires clinicians to incorporate both
      tooth and gingival esthetics. When gingivectomies and crown-lengthening
      procedures are required, opting for direct nanohybrid composite restorations can
      help enable dentists to achieve harmonious blending of the gingival architecture
      and the anticipated restoration by allowing for tissue healing and subsequent
      modifications to the gingival portions of restorations. This article presents two
      cases in which anterior nanohybrid direct composite restorations provided a means
      to enhance tooth esthetics simultaneous to improving gingival harmony. 

PMID- 24568219
TI  - The uremic toxin indoxyl sulfate acts as a pro- or antioxidant on LDL oxidation.
AB  - Uremic toxins have been shown to play a role in chronic kidney disease (CKD)
      associated oxidative stress. Oxidative stress and inflammation have been
      associated with increased risk of cardiovascular disease in uraemia. The
      oxidative modification of LDL may play a role in early atherogenesis. Enhanced
      LDL oxidation has been found in uremic patients which may account for accelerated
      atherosclerosis observed in CKD. The uremic toxin indoxyl sulfate (IS) has been
      reported to exert oxidative and antioxidative activity. Thus, in the present
      study we have investigated the influence of IS on the atherogenic modifications
      of LDL exposed in vitro to different oxidising systems. The transition metal ion
      (Cu(2+)) and hemin/H2O2 induced lipid oxidation reactions monitored by conjugated
      diene formation, were inhibited by the presence of IS, which points to possible
      antioxidant effects by this uremic toxin. A protective effect of IS on LDL
      apoprotein modification by the exposure to the product of the
      myeloperoxidase/H2O2/Cl(-) system HOCl, was also observed as estimated by protein
      carbonyl formation. In contrast, a marked increase in conjugated dienes and lipid
      hydroperoxides was observed when lipid oxidation was initiated by the free
      radical generator AAPH in presence of IS. The GC-MS analysis revealed the
      formation of indole-2,3-dione and 6,12-dihydro-6,12-dioxo-indolo[2,1
      b]quinazoline (tryptanthrin) in IS/AAPH reaction. A scheme for the generation of
      tryptanthrin from IS via indoxyl radicals is proposed, which may facilitate LDL
      lipid oxidation. Our observations add further insight in the Janus-faced
      properties of this important uremic toxin.

PMID- 24568220
TI  - Dual adeno-associated virus vectors result in efficient in vitro and in vivo
      expression of an oversized gene, MYO7A.
AB  - Usher syndrome 1B (USH1B) is a severe, autosomal recessive, deaf-blind disorder
      caused by mutations in myosin 7A (MYO7A). Patients are born profoundly deaf and
      exhibit progressive loss of vision starting in their first decade. MYO7A is
      expressed in human photoreceptors and retinal pigment epithelium, but disease
      pathology begins in photoreceptors, highlighting the need to develop a gene
      replacement strategy that effectively targets this cell type. For its safety and
      efficacy in clinical trials and ability to transduce postmitotic photoreceptors,
      we have focused on developing a clinically applicable adeno-associated virus
      (AAV) platform for delivering full-length MYO7A cDNA (~6.7 kb). Packaging of full
      length MYO7A cDNA in AAV produces vectors with heterogeneous, fragmented genomes
      ("fAAV") capable of reconstituting full-length cDNA postinfection. We previously
      showed that fAAV vectors effectively delivered full-length MYO7A in vitro and in
      vivo. However, fAAV vectors are relatively inefficient and their heterogeneous
      genomes preclude definitive characterization, a drawback for clinical
      translatability. The aim of this study was to overcome these limitations by
      creating dual-AAV-vector platforms for USH1B with defined genomes. Human MYO7A
      was cloned in AAV vector pairs, each containing genomes <5 kb and intact inverted
      terminal repeats. One vector contained a promoter and 5' portion of the cDNA and
      the partner vector contained a 3' portion and polyadenylation signal. "Simple
      overlap" vectors share a central part of the MYO7A cDNA sequence. "Trans
      splicing" and "hybrid" vectors utilize splice donor and acceptor sites with and
      without an additional central recombinogenic sequence, respectively. Vector pairs
      expressed full-length MYO7A in vitro and in vivo with equal or higher efficiency
      than fAAV, with a hybrid platform being most efficient. Importantly, analysis of
      MYO7A mRNA derived from each dual-vector platform revealed 100% fidelity to the
      predicted sequence. Our results suggest that dual AAV vectors with defined
      genetic payloads are a potential treatment option for USH1B.

PMID- 24568221
TI  - Characterization of Neisseria gonorrhoeae isolates detected in Switzerland (1998
      2012): emergence of multidrug-resistant clones less susceptible to
      cephalosporins.
AB  - BACKGROUND: The spread of Neisseria gonorrhoeae (Ng) isolates resistant to the
      clinically implemented antibiotics is challenging the efficacy of treatments.
      Unfortunately, phenotypic and molecular data regarding Ng detected in Switzerland
      are scarce. METHODS: We compared the characteristics of Ng detected during 1998
      2001 (n = 26) to those detected during 2009-2012 (n = 34). MICs were obtained
      with the Etest and interpreted as non-susceptible (non-S) according to EUCAST
      criteria. Sequence type (ST) was achieved implementing the NG-MAST. BlaTEM, ponA,
      penA, mtrR, penB, tet(M), gyrA, parC, mefA, ermA/B/C/F, rplD, rplV, and 23S rRNA
      genes were analyzed. RESULTS: The following susceptibility results were obtained
      (period: % of non-S, MIC90 in mg/L): penicillin (1998-2001: 42.3%, 3; 2009-2012:
      85.3%, 16), cefixime (1998-2001: 0%, <=0.016; 2009-2012: 8.8%, 0.125),
      ceftriaxone (1998-2001: 0%, 0.004; 2009-2012: 0%, 0.047), ciprofloxacin (1998
      2001: 7.7%, 0.006; 2009-2012: 73.5%, >=32), azithromycin (1998-2001: 11.5%, 0.25;
      2009-2012: 23.6%, 0.38), tetracycline (1998-2001: 65.4%, 12; 2009-2012: 88.2%,
      24), spectinomycin (1998-2001: 0%, 12; 2009-2012: 0%, 8). The prevalence of
      multidrug-resistant (MDR) isolates increased from 7.7% in 1998-2001 to 70.6% in
      2009-2012. International STs and genogroups (G) emerged during 2009-2012 (G1407,
      29.4%; G2992, 11.7%; G225, 8.8%). These isolates possessed distinctive mechanisms
      of resistance (e.g., G1407: PBP1 with L421, PBP2 pattern XXXIV, GyrA with S91F
      and D95G, ParC with S87R, PorB with G120K and A121N, mtrR promoter with A
      deletion). CONCLUSIONS: The prevalence of penicillin- ciprofloxacin- and
      tetracycline-resistant Ng has reached dramatic levels, whereas cefixime and
      ceftriaxone show MICs that tend to increase during time. International MDR clones
      less susceptible to cephalosporins are rapidly emerging indicating that the era
      of untreatable gonococcal infections is close.

PMID- 24568223
TI  - Joint stability characteristics of the ankle complex in female athletes with
      histories of lateral ankle sprain, part II: clinical experience using
      arthrometric measurement.
AB  - CONTEXT: This is part II of a 2-part series discussing stability characteristics
      of the ankle complex. In part I, we used a cadaver model to examine the effects
      of sectioning the lateral ankle ligaments on anterior and inversion motion and
      stiffness of the ankle complex. In part II, we wanted to build on and apply these
      findings to the clinical assessment of ankle-complex motion and stiffness in a
      group of athletes with a history of unilateral ankle sprain. OBJECTIVE: To
      examine ankle-complex motion and stiffness in a group of athletes with reported
      history of lateral ankle sprain. DESIGN: Cross-sectional study. SETTING:
      University research laboratory. PATIENTS OR OTHER PARTICIPANTS: Twenty-five
      female college athletes (age = 19.4 +/- 1.4 years, height = 170.2 +/- 7.4 cm,
      mass = 67.3 +/- 10.0 kg) with histories of unilateral ankle sprain.
      INTERVENTION(S): All ankles underwent loading with an ankle arthrometer. Ankles
      were tested bilaterally. MAIN OUTCOME MEASURE(S): The dependent variables were
      anterior displacement, anterior end-range stiffness, inversion rotation, and
      inversion end-range stiffness. RESULTS: Anterior displacement of the ankle
      complex did not differ between the uninjured and sprained ankles (P = .37),
      whereas ankle-complex rotation was greater for the sprained ankles (P = .03). The
      sprained ankles had less anterior and inversion end-range stiffness than the
      uninjured ankles (P < .01). CONCLUSIONS: Changes in ankle-complex laxity and end
      range stiffness were detected in ankles with histories of sprain. These results
      indicate the presence of altered mechanical characteristics in the soft tissues
      of the sprained ankles.

PMID- 24568222
TI  - Targeting the prohibitin scaffold-CRAF kinase interaction in RAS-ERK-driven
      pancreatic ductal adenocarcinoma.
AB  - BACKGROUND: Robust ERK1/2 activity, which frequently results from KRAS mutation,
      invariably occurs in pancreatic ductal adenocarcinoma (PDAC). However, direct
      interference of KRAS signaling has not led to clinically successful drugs.
      Correct localization of RAF is regulated by the scaffold protein prohibitin (PHB)
      that ensures the spatial organization between RAS and RAF in plasma membranes,
      thus leading to activation of downstream effectors. METHODS: PHB expression was
      analyzed in human pancreatic cancer cell lines, normal pancreas, and PDAC tissue.
      Furthermore, genetic ablation or pharmacological inhibition of PHB was performed
      to determine its role in growth, migration, and signaling of pancreatic cancer
      cells in vitro and in vivo. RESULTS: The level of PHB expression was crucial for
      maintenance of oncogenic ERK-driven pancreatic tumorigenesis. Additionally,
      rocaglamide (RocA), a small molecular inhibitor, selectively bound to PHB with
      nanomolar affinity to disrupt the PHB-CRAF interaction by altering its
      localization to the plasma membrane. Consequently, there was an impairment of
      oncogenic RAS-ERK signaling, thereby blocking in vitro and in vivo growth and
      metastasis of pancreatic cancer cells that were addicted to RAS-ERK signaling.
      More importantly, RocA treatment resulted in a significant increase of the
      lifespan of tumor-bearing mice without any detectable toxicity. CONCLUSIONS:
      Blockade of the PHB scaffold-CRAF kinase interaction, which is distinct from
      direct kinase inhibition, may be a new therapeutic strategy to target oncogenic
      ERK-driven pancreatic cancer.

PMID- 24568224
TI  - Lower extremity biomechanics in athletes with ankle instability after a 6-week
      integrated training program.
AB  - CONTEXT: Plyometric exercise has been recommended to prevent lower limb injury,
      but its feasibility in and effects on those with functional ankle instability
      (FAI) are unclear. OBJECTIVE: To investigate the effect of integrated plyometric
      and balance training in participants with FAI during a single-legged drop landing
      and single-legged standing position. DESIGN: Randomized controlled clinical
      trial. SETTING: University motion-analysis laboratory. PATIENTS OR OTHER
      PARTICIPANTS: Thirty athletes with FAI were divided into 3 groups: plyometric
      group (8 men, 2 women, age = 23.20 +/- 2.82 years; 10 unstable ankles),
      plyometric-balance (integrated)-training group (8 men, 2 women, age = 23.80 +/-
      4.13 years; 10 unstable ankles), and control group (7 men, 3 women, age = 23.50
      +/- 3.00 years; 10 unstable ankles). INTERVENTION(S): A 6-week plyometric
      training program versus a 6-week integrated-training program. MAIN OUTCOME
      MEASURE(S): Postural sway during single-legged standing with eyes open and closed
      was measured before and after training. Kinematic data were recorded during
      medial and lateral single-legged drop landings after a 5-second single-legged
      stance. RESULTS: Reduced postural sway in the medial-lateral direction and
      reduced sway area occurred in the plyometric- and integrated-training groups.
      Generally, the plyometric training and integrated training increased the maximum
      angles at the hip and knee in the sagittal plane, reduced the maximum angles at
      the hip and ankle in the frontal and transverse planes in the lateral drop
      landing, and reduced the time to stabilization for knee flexion in the medial
      drop landing. CONCLUSIONS: After 6 weeks of plyometric training or integrated
      training, individuals with FAI used a softer landing strategy during drop
      landings and decreased their postural sway during the single-legged stance.
      Plyometric training improved static and dynamic postural control and should be
      incorporated into rehabilitation programs for those with FAI.

PMID- 24568225
TI  - Pre-exercise ingestion of pickle juice, hypertonic saline, or water and aerobic
      performance and thermoregulation.
AB  - CONTEXT: Ingesting high-sodium drinks pre-exercise can improve thermoregulation
      and performance. Athletic trainers (19%) give athletes pickle juice (PJ)
      prophylactically for cramping. No data exist on whether this practice affects
      aerobic performance or thermoregulation. OBJECTIVE: To determine if drinking 2
      mL/kg body mass of PJ, hypertonic saline, or deionized water (DIW) pre-exercise
      affects aerobic performance or thermoregulation. DESIGN: Crossover study.
      SETTING: Controlled laboratory study. PATIENTS OR OTHER PARTICIPANTS: Nine
      euhydrated men (age = 22 +/- 3 years, height = 184.0 +/- 8.2 cm, mass = 82.6 +/-
      16.0 kg) completed testing. INTERVENTION(S): Participants rested for 65 minutes.
      During this period, they ingested 2 mL/kg of PJ, hypertonic saline, or DIW. Next,
      they drank 5 mL/kg of DIW. Blood was collected before and after ingestion of all
      fluids. Participants were weighed and ran in the heat (temperature = 38.3 degrees
      C +/- 1 degrees C, relative humidity = 21.1% +/- 4.7%) at increasing increments
      of maximal heart rate (50%, 60%, 70%, 80%, 90%, 95%) until exhaustion or until
      rectal temperature exceeded 39.5 degrees C. Participants were weighed
      postexercise so we could calculate sweat volume. MAIN OUTCOME MEASURE(S): Time to
      exhaustion, rectal temperature, changes in plasma volume, and sweat volume.
      RESULTS: Time to exhaustion did not differ among drinks (PJ = 77.4 +/- 5.9
      minutes, hypertonic saline = 77.4 +/- 4.0 minutes, DIW = 75.7 +/- 3.2 minutes;
      F2,16 = 1.1, P = .40). Core temperature of participants was similar among drinks
      (PJ = 38.7 degrees C +/- 0.3 degrees C, hypertonic saline = 38.7 degrees C +/-
      0.4 degrees C, DIW = 38.8 degrees C +/- 0.4 degrees C; P = .74) but increased
      from pre-exercise (36.7 degrees C +/- 0.2 degrees C) to postexercise (38.7
      degrees C +/- 0.4 degrees C) (P < .05). No differences were observed for changes
      in plasma volume or sweat volume among drinks (P > .05). CONCLUSIONS: Ingesting
      small amounts of PJ or hypertonic saline with water did not affect performance or
      select thermoregulatory measures. Drinking larger volumes of PJ and water may be
      more effective at expanding the extracellular space.

PMID- 24568226
TI  - The relationship among foot posture, core and lower extremity muscle function,
      and postural stability.
AB  - CONTEXT: Identification of impaired balance as a risk factor for lower extremity
      injury regardless of injury history has led to subsequent investigation of
      variables that may adversely affect balance in healthy individuals. OBJECTIVES:
      To investigate the relationship among core and lower extremity muscle function,
      foot posture, and balance. DESIGN: Descriptive laboratory study. SETTING:
      Musculoskeletal injury biomechanics laboratory. PATIENTS OR OTHER PARTICIPANTS: A
      total of 108 individuals (40 men, 68 women; age = 22.8 +/- 4.7 years, height =
      168.5 +/- 10.4 cm, mass = 69.9 +/- 13.3 kg) participated in the study. MAIN
      OUTCOME MEASURE(S): Core endurance was assessed during 1 time-to-failure trial,
      and isometric hip and ankle strength were assessed using a handheld dynamometer
      and isokinetic dynamometer, respectively. Foot structure was quantified using the
      digital photographic measurement method. Single-limb-stance time to boundary was
      assessed using a force plate during an eyes-closed condition. Hierarchical
      multiple regression analyses were performed to predict balance using lower
      extremity strength, foot posture, and core endurance. RESULTS: Foot posture (beta
      = -0.22, P = .03) and ankle-inversion strength (beta = -0.29, P = .006) predicted
      mediolateral balance. Increasing arch posture and ankle-inversion strength were
      associated with decreased mediolateral single-limb-stance balance. CONCLUSIONS:
      Increasing arch height was associated with decreased mediolateral control of
      single-limb stance. The relationship between time to boundary and injury risk,
      however, has not been explored. Therefore, the relationship between increasing
      arch height and injury due to postural instability cannot be determined from this
      study. If authors of future prospective studies identify a relationship between
      decreased time to boundary and increased injury risk, foot structure may be an
      important variable to assess during preparticipation physical examinations. The
      relationship between increasing ankle-inversion strength and decreased balance
      may require additional study to further elucidate the relationship between ankle
      strength and balance.

PMID- 24568227
TI  - Fatigue-induced balance impairment in young soccer players.
AB  - CONTEXT: Although balance is generally recognized to be an important feature in
      ensuring good performance in soccer, its link with functional performance remains
      mostly unexplored, especially in young athletes. OBJECTIVE: To investigate
      changes in balance induced by fatigue for unipedal and bipedal static stances in
      young soccer players. DESIGN: Crossover study. SETTING: Biomechanics laboratory
      and outdoor soccer field. PATIENTS OR OTHER PARTICIPANTS: Twenty-one male soccer
      players (age = 14.5 +/- 0.2 years, height = 164.5 +/- 5.6 cm, mass = 56.8 +/- 6.8
      kg). INTERVENTION(S): Static balance was assessed with postural-sway analysis in
      unipedal and bipedal upright stance before and after a fatigue protocol
      consisting of a repeated sprint ability (RSA) test (2 * 15-m shuttle sprint
      interspersed with 20 seconds of passive recovery, repeated 6 times). MAIN OUTCOME
      MEASURE(S): On the basis of the center-of-pressure (COP) time series acquired
      during the experimental tests, we measured sway area, COP path length, and COP
      maximum displacement and velocity in the anteroposterior and mediolateral
      directions. RESULTS: Fatigue increased all sway values in bipedal stance and all
      values except COP velocity in the mediolateral direction in unipedal stance.
      Fatigue index (calculated on the basis of RSA performance) was positively
      correlated with fatigue/rest sway ratio for COP path length and COP velocity in
      the anteroposterior and mediolateral directions for nondominant single-legged
      stance. CONCLUSIONS: Fatigued players exhibited reduced performance of the
      postural-control system. Participants with better performance in the RSA test
      appeared less affected by balance impairment, especially in single-legged stance.

PMID- 24568228
TI  - An evidence-based practice educational intervention for athletic trainers: a
      randomized controlled trial.
AB  - CONTEXT: As evidence-based practice (EBP) becomes a necessity in athletic
      training, Web-based modules have been developed and made available to the
      National Athletic Trainers' Association membership as a mechanism to educate
      athletic trainers (ATs) on concepts of EBP. OBJECTIVE: To assess the effect of an
      educational intervention on enhancing knowledge of EBP among ATs. DESIGN:
      Randomized controlled trial. SETTING: Web-based modules and knowledge assessment.
      PATIENTS OR OTHER PARTICIPANTS: A total of 164 of 473 ATs (34.7% response rate),
      including professional athletic training students, graduate students, clinical
      preceptors, educators, and clinicians, were randomized into a control group (40
      men, 42 women) or experimental group (33 men, 49 women). INTERVENTION(S): Ten Web
      based modules were developed that covered concepts involved in the EBP process.
      Both groups completed the Evidence-Based Practice Knowledge Assessment before and
      after the intervention phase. During the intervention phase, the experimental
      group had access to the Web-based modules for 4 weeks, whereas the control group
      had no direct responsibilities for the investigation. The knowledge assessment
      consisted of 60 multiple choice questions pertaining to concepts presented in the
      10 modules. Test-retest reliability was determined to be good (intraclass
      correlation coefficient [2,1] = 0.726, 95% confidence interval = 0.605, 0.814).
      MAIN OUTCOME MEASURE(S): Independent variables consisted of group (control,
      experimental) and time (preassessment, postassessment). Knowledge scores were
      tabulated by awarding 1 point for each correct answer (maximum = 60). Between
      group and within-group differences were calculated using a 2 * 2 repeated
      measures analysis of variance (P <= .05), post hoc t tests, and Hedges g effect
      size with 95% confidence intervals. RESULTS: We found a group * time interaction
      (F1,162 = 26.29, P < .001). No differences were identified between the control
      (30.12 +/- 5.73) and experimental (30.65 +/- 5.93) groups during the
      preassessment (t162 = 0.58, P = .84). The experimental group (36.35 +/- 8.58)
      obtained higher scores on the postassessment than the control group (30.99 +/-
      6.33; t162 = 4.55, P = .01). No differences were identified among time instances
      within the control group (t81 = 1.77, P = .08); however, the experimental group
      obtained higher scores on the postassessment than the preassessment (t81 = 7.07,
      P < .001). CONCLUSIONS: An educational intervention consisting of 10 Web-based
      modules was an effective mechanism to increase knowledge of foundational EBP
      concepts among ATs. However, it is not known whether ATs are integrating EBP into
      daily clinical practice. Researchers should determine whether increased knowledge
      of EBP affects the daily clinical decision making of ATs.

PMID- 24568229
TI  - Jump-landing biomechanics and knee-laxity change across the menstrual cycle in
      women with anterior cruciate ligament reconstruction.
AB  - CONTEXT: Of the individuals able to return to sport participation after an
      anterior cruciate ligament(ACL) injury, up to 25% will experience a second ACL
      injury. This population may be more sensitive to hormonal fluctuations, which may
      explain this high rate of second injury. OBJECTIVE: To examine changes in 3
      dimensional hip and knee kinematics and kinetics during a jump landing and to
      examine knee laxity across the menstrual cycle in women with histories of
      unilateral noncontact ACL injury. DESIGN: Controlled laboratory study. SETTING:
      Laboratory. PATIENTS OR OTHER PARTICIPANTS: A total of 20 women (age = 19.6 +/-
      1.3 years, height = 168.6 +/- 5.3 cm, mass = 66.2 +/- 9.1 kg) with unilateral,
      noncontact ACL injuries. INTERVENTION(S): Participants completed a jump-landing
      task and knee-laxity assessment 3 to 5 days after the onset of menses and within
      3 days of a positive ovulation test. MAIN OUTCOME MEASURE(S): Kinematics in the
      uninjured limb at initial contact with the ground during a jump landing, peak
      kinematics and kinetics during the loading phase of landing, anterior knee laxity
      via the KT-1000, peak vertical ground reaction force, and blood hormone
      concentrations (estradiol-beta-17, progesterone, free testosterone). RESULTS: At
      ovulation, estradiol-beta-17 (t = -2.9, P = .009), progesterone (t = -3.4, P =
      .003), and anterior knee laxity (t = -2.3, P = .03) increased, and participants
      presented with greater knee-valgus moment (Z = -2.6, P = .01) and femoral
      internal rotation (t = -2.1, P = .047). However, during the menses test session,
      participants landed harder (greater peak vertical ground reaction force; t = 2.2,
      P = .04), with the tibia internally rotated at initial contact (t = 2.8, P = .01)
      and greater hip internal-rotation moment (Z = -2.4, P = .02). No other changes
      were observed across the menstrual cycle. CONCLUSIONS: Knee and hip mechanics in
      both phases of the menstrual cycle represented a greater potential risk of ACL
      loading. Observed changes in landing mechanics may explain why the risk of second
      ACL injury is elevated in this population.

PMID- 24568231
TI  - Bilateral improvements in lower extremity function after unilateral balance
      training in individuals with chronic ankle instability.
AB  - CONTEXT: Bilateral improvements in postural control have been reported among
      individuals with acute lateral ankle sprains and individuals with chronic ankle
      instability (CAI) when only the unstable ankle is rehabilitated. We do not know
      if training the stable ankle will improve function on the unstable side.
      OBJECTIVE: To explore the effects of a unilateral balance-training program on
      bilateral lower extremity balance and function in individuals with CAI when only
      the stable limb is trained. DESIGN: Cohort study. SETTING: University clinical
      research laboratory. PATIENTS OR OTHER PARTICIPANTS: A total of 34 volunteers (8
      men, 26 women; age = 24.32 +/- 4.95 years, height = 167.01 +/- 9.45 cm, mass =
      77.54 +/- 23.76 kg) with CAI were assigned to the rehabilitation (n = 17) or
      control (n = 17) group. Of those, 27 (13 rehabilitation group, 14 control group)
      completed the study. INTERVENTION(S): Balance training twice weekly for 4 weeks.
      MAIN OUTCOME MEASURE(S): Foot and Ankle Disability Index (FADI), FADI Sport (FADI
      S), Star Excursion Balance Test, and Balance Error Scoring System. RESULTS: The
      rehabilitation and control groups differed in changes in FADI-S and Star
      Excursion Balance Test scores over time. Only the rehabilitation group improved
      in the FADI-S and in the posteromedial and anterior reaches of the Star Excursion
      Balance Test. Both groups demonstrated improvements in posterolateral reach;
      however, the rehabilitation group demonstrated greater improvement than the
      control group. When the groups were combined, participants reported improvements
      in FADI and FADI-S scores for the unstable ankle but not the stable ankle.
      CONCLUSIONS: Our data suggest training the stable ankle may result in
      improvements in balance and lower extremity function in the unstable ankle. This
      further supports the existence of a centrally mediated mechanism in the
      development of postural-control deficits after injury, as well as improved
      postural control after rehabilitation.

PMID- 24568230
TI  - Future directions of evidence-based practice in athletic training: perceived
      strategies to enhance the use of evidence-based practice.
AB  - CONTEXT: The shift to a culture of evidence-based practice (EBP) in athletic
      training is a necessary step in both the optimization of patient care and the
      advancement of athletic trainers (ATs) as health care professionals. Whereas
      individuals have gained knowledge in this area, most ATs still are not practicing
      in an evidence-based manner. Exploring perceived strategies to enhance the use of
      EBP will help to determine the best approaches to assist ATs in applying EBP
      concepts to practice to improve patient care. OBJECTIVE: To explore beneficial
      strategies and techniques ATs perceived would promote successful implementation
      of EBP within athletic training education and clinical practice. DESIGN:
      Qualitative study. SETTING: Individual telephone interviews. PATIENTS OR OTHER
      PARTICIPANTS: Twenty-five ATs (12 educators, 13 clinicians; athletic training
      experience = 16.00 +/- 9.41 years) were interviewed. DATA COLLECTION AND
      ANALYSIS: One phone interview was conducted with each participant. After the
      interview was transcribed, the data were analyzed and coded into common themes
      and categories. Triangulation of the data occurred via the use of multiple
      researchers and member checking to confirm the accuracy of the data. RESULTS:
      Participants identified several components they perceived as essential for
      enhancing the use of EBP within the athletic training profession. These
      components included the need for more EBP resources, more processed information,
      focused workshops, peer discussion and mentorship, and continual repetition and
      exposure. Participants also indicated that ATs need to accept their professional
      responsibilities to foster EBP in their daily practices. CONCLUSIONS: The proper
      shift to a culture of EBP in athletic training will take both time and a
      persistent commitment by ATs to create strategies that will enhance the
      implementation of EBP across the profession. Researchers should focus on
      continuing to identify effective educational interventions for ATs and to
      determine successful strategies to implement EBP into didactic curricula and
      clinical practice. Additional focus should be given to which strategies most
      effectively produce changes in clinical practice.

PMID- 24568232
TI  - Joint stability characteristics of the ankle complex after lateral ligamentous
      injury, part I: a laboratory comparison using arthrometric measurement.
AB  - CONTEXT: The mechanical property of stiffness may be important to investigating
      how lateral ankle ligament injury affects the behavior of the viscoelastic
      properties of the ankle complex. A better understanding of injury effects on
      tissue elastic characteristics in relation to joint laxity could be obtained from
      cadaveric study. OBJECTIVE: To biomechanically determine the laxity and stiffness
      characteristics of the cadaver ankle complex before and after simulated injury to
      the anterior talofibular ligament (ATFL) and calcaneofibular ligament (CFL)
      during anterior drawer and inversion loading. DESIGN: Cross-sectional study.
      SETTING: University research laboratory. PATIENTS OR OTHER PARTICIPANTS: Seven
      fresh-frozen cadaver ankle specimens. INTERVENTION(S): All ankles underwent
      loading before and after simulated lateral ankle injury using an ankle
      arthrometer. MAIN OUTCOME MEASURE(S): The dependent variables were anterior
      displacement, anterior end-range stiffness, inversion rotation, and inversion end
      range stiffness. RESULTS: Isolated ATFL and combined ATFL and CFL sectioning
      resulted in increased anterior displacement but not end-range stiffness when
      compared with the intact ankle. With inversion loading, combined ATFL and CFL
      sectioning resulted in increased range of motion and decreased end-range
      stiffness when compared with the intact and ATFL-sectioned ankles. CONCLUSIONS:
      The absence of change in anterior end-range stiffness between the intact and
      ligament-deficient ankles indicated bony and other soft tissues functioned to
      maintain stiffness after pathologic joint displacement, whereas inversion loading
      of the CFL-deficient ankle after pathologic joint displacement indicated the
      ankle complex was less stiff when supported only by the secondary joint
      structures.

PMID- 24568234
TI  - N-terminal alpha-ketoamide peptides: formation and transamination.
AB  - We have previously reported that N-terminal alpha-ketoamide peptides can be
      formed through 4-oxo-2(E)-nonenal (ONE)-derived oxidative decarboxylation of
      aspartic acid (Asp), which converts angiotensin (Ang) II (DRVYIHPF) to pyruvamide
      Ang II (Ang P, CH3COCONH-RVYIHPF). The pyruvamide group significantly inhibits
      Ang P binding to the Ang II type 1 receptor, which mediates the major biological
      effects of Ang II. In the present study, we found that ONE can also introduce an
      alpha-ketoamide moiety at the N-terminus of peptides containing N-terminal
      residues other than Asp. Subsequent investigation of alternative biosynthetic
      pathways for N-terminal alpha-ketoamide peptides revealed that hydroxyl radical
      mediated formation is a much more efficient route. The proposed mechanism
      involves initial abstraction of the N-terminal alpha-hydrogen and hydrolysis of
      the ketimine intermediate. The resulting N-terminal alpha-ketoamide is then
      converted to the D- and L-amino acids by nonenzymatic transamination in the
      presence of pyridoxamine (PM). The formation of the epimeric N-terminus depended
      on the incubation time and the concentration of PM, and increased further upon
      the addition of Cu(II) ions. A conversion of approximately 60% after three days
      of incubation was observed for Ang P. We propose that the reaction intermediate
      contains a prochiral alpha-carbon and is stabilized by the chelate effect of
      Cu(II) ions. The ONE- and hydroxyl radical-derived formation of N-terminal alpha
      ketoamide and its transamination in the presence of PM were also observed in
      amyloid beta 1-11 (DAEFRHDSGYE), where the N-terminal Asp was converted to
      epimeric alanine. This suggests that these N-terminal modifications could occur
      in vivo and modulate the biological functions of peptides and proteins.

PMID- 24568235
TI  - Influence of aqueous media on the ROS-mediated toxicity of ZnO nanoparticles
      toward green fluorescent protein-expressing Escherichia coli under UV-365
      irradiation.
AB  - The aqueous media could affect the physicochemical properties (e.g., surface
      charge, morphology, and aggregation) of ZnO nanoparticles (nZnO), leading to
      their different environmental impacts. In this study, the toxicity of nZnO toward
      the green fluorescent protein-expressing Escherichia coli cells under UV-365
      light irradiaiton in various media was assessed, including deionized (DI) water,
      0.85% NaCl, phosphate-buffered saline (PBS), minimal Davis medium (MD), and Luria
      Bertani medium (LB). The toxicity of nZnO was assessed by the conventional plate
      count method and the fluorescence intensity method, which consistently
      demonstrated that the nZnO toxicity was dependent on the medium components that
      varied the potency of reactive oxygen species (ROS) generation. In DI, NaCl, PBS,
      and MD medium, nZnO generated three types of ROS (O2(*-), *OH, and (1)O2),
      whereas in LB medium, nZnO generated O2(*-) and (1)O2. The total concentrations
      of ROS generated by nZnO in DI, NaCl, PBS, MD, and LB were 265.5 +/- 15.9, 153.6
      +/- 8.6, 144.3 +/- 6.9, 123.0 +/- 6.0, and 115.6 +/- 4.5 MUM, respectively.
      Furthermore, a linear correlation was established between the total
      concentrations of three types of ROS generated by nZnO and their bacterial
      mortality rate (R(2) = 0.92) in various media. Since the released Zn(2+) from
      nZnO under UV irradiation only accounted for less than 10% of the total Zn in all
      media, the ionic forms of zinc did not significantly contribute to the overall
      toxicity. This work aims at providing further insight into the medium type
      influences on the ROS production and the toxicity of nZnO toward the E. coli
      cells. 

PMID- 24568233
TI  - Significant improvements in cognitive performance post-transcranial, red/near
      infrared light-emitting diode treatments in chronic, mild traumatic brain injury:
      open-protocol study.
AB  - This pilot, open-protocol study examined whether scalp application of red and
      near-infrared (NIR) light-emitting diodes (LED) could improve cognition in
      patients with chronic, mild traumatic brain injury (mTBI). Application of red/NIR
      light improves mitochondrial function (especially in hypoxic/compromised cells)
      promoting increased adenosine triphosphate (ATP) important for cellular
      metabolism. Nitric oxide is released locally, increasing regional cerebral blood
      flow. LED therapy is noninvasive, painless, and non-thermal (cleared by the
      United States Food and Drug Administration [FDA], an insignificant risk device).
      Eleven chronic, mTBI participants (26-62 years of age, 6 males) with
      nonpenetrating brain injury and persistent cognitive dysfunction were treated for
      18 outpatient sessions (Monday, Wednesday, Friday, for 6 weeks), starting at 10
      months to 8 years post- mTBI (motor vehicle accident [MVA] or sports-related; and
      one participant, improvised explosive device [IED] blast injury). Four had a
      history of multiple concussions. Each LED cluster head (5.35 cm diameter, 500 mW,
      22.2 mW/cm(2)) was applied for 10 min to each of 11 scalp placements (13
      J/cm(2)). LEDs were placed on the midline from front-to-back hairline; and
      bilaterally on frontal, parietal, and temporal areas. Neuropsychological testing
      was performed pre-LED, and at 1 week, and 1 and 2 months after the 18th
      treatment. A significant linear trend was observed for the effect of LED
      treatment over time for the Stroop test for Executive Function, Trial 3
      inhibition (p=0.004); Stroop, Trial 4 inhibition switching (p=0.003); California
      Verbal Learning Test (CVLT)-II, Total Trials 1-5 (p=0.003); and CVLT-II, Long
      Delay Free Recall (p=0.006). Participants reported improved sleep, and fewer post
      traumatic stress disorder (PTSD) symptoms, if present. Participants and family
      reported better ability to perform social, interpersonal, and occupational
      functions. These open-protocol data suggest that placebo-controlled studies are
      warranted.

PMID- 24568236
TI  - Pulmonary diesel particulate increases susceptibility to myocardial
      ischemia/reperfusion injury via activation of sensory TRPV1 and beta1
      adrenoreceptors.
AB  - BACKGROUND: Clinical studies have now confirmed the link between short-term
      exposure to elevated levels of air pollution and increased cardiovascular
      mortality, but the mechanisms are complex and not completely elucidated. The
      present study was designed to investigate the hypothesis that activation of
      pulmonary sensory receptors and the sympathetic nervous system underlies the
      influence of pulmonary exposure to diesel exhaust particulate on blood pressure,
      and on the myocardial response to ischemia and reperfusion. METHODS & RESULTS: 6
      h after intratracheal instillation of diesel exhaust particulate (0.5 mg),
      myocardial ischemia and reperfusion was performed in anesthetised rats. Blood
      pressure, duration of ventricular arrhythmia, arrhythmia-associated death, tissue
      edema and reperfusion injury were all increased by diesel exhaust particulate
      exposure. Reperfusion injury was also increased in buffer perfused hearts
      isolated from rats instilled in vivo, excluding an effect dependent on continuous
      neurohumoral activation or systemic inflammatory mediators. Myocardial oxidant
      radical production, tissue apoptosis and necrosis were increased prior to
      ischemia, in the absence of recruited inflammatory cells. Intratracheal
      application of an antagonist of the vanilloid receptor TRPV1 (AMG 9810, 30 mg/kg)
      prevented enhancement of systolic blood pressure and arrhythmia in vivo, as well
      as basal and reperfusion-induced myocardial injury ex vivo. Systemic beta1
      adrenoreceptor antagonism with metoprolol (10 mg/kg) also blocked enhancement of
      myocardial oxidative stress and reperfusion injury. CONCLUSIONS: Pulmonary diesel
      exhaust particulate increases blood pressure and has a profound adverse effect on
      the myocardium, resulting in tissue damage, but also increases vulnerability to
      ischemia-associated arrhythmia and reperfusion injury. These effects are mediated
      through activation of pulmonary TRPV1, the sympathetic nervous system and locally
      generated oxidative stress.

PMID- 24568237
TI  - Dynamics associated with spontaneous differentiation of ovarian stem cells in
      vitro.
AB  - BACKGROUND: Recent studies suggest that ovarian germ line stem cells replenish
      oocyte-pool in adult stage, and challenge the central doctrine of 'fixed germ
      cell pool' in mammalian reproductive biology. Two distinct populations of
      spherical stem cells with high nucleo-cytoplasmic ratio have been recently
      identified in the adult mammalian ovary surface epithelium (OSE) including
      nuclear OCT-4A positive very small embryonic-like (VSELs) and cytoplasmic OCT-4
      expressing ovarian germ stem cells (OGSCs). Three weeks culture of scraped OSE
      cells results in spontaneous differentiation of the stem cells into oocyte-like,
      parthenote-like, embryoid body-like structures and also embryonic stem cell-like
      colonies whereas epithelial cells attach and transform into a bed of mesenchymal
      cells. Present study was undertaken, to further characterize ovarian stem cells
      and to comprehend better the process of spontaneous differentiation of ovarian
      stem cells into oocyte-like structures in vitro. METHODS: Ovarian stem cells were
      enriched by immunomagnetic sorting using SSEA-4 as a cell surface marker and were
      further characterized. Stem cells and clusters of OGSCs (reminiscent of germ cell
      nests in fetal ovaries), were characterized by immuno-localization for stem and
      germ cell specific markers and spontaneous differentiation in OSE cultures was
      studied by live cell imaging. RESULTS: Differential expression of markers
      specific for pluripotent VSELs (nuclear OCT-4A, SSEA-4, CD133), OGSCs
      (cytoplasmic OCT-4) primordial germ cells (FRAGILIS, STELLA, VASA) and germ cells
      (DAZL, GDF-9, SCP-3) were studied. Within one week of culture, stem cells became
      bigger in size, developed abundant cytoplasm, differentiated into germ cells,
      revealed presence of Balbiani body-like structure (mitochondrial cloud) and
      exhibited characteristic cytoplasmic streaming. CONCLUSIONS: Presence of germ
      cell nests, Balbiani body-like structures and cytoplasmic streaming extensively
      described during fetal ovary development, are indeed well recapitulated during in
      vitro oogenesis in adult OSE cultures along with characteristic expression of
      stem/germ cell/oocyte markers. Further studies are required to assess the genetic
      integrity of in vitro derived oocytes before harnessing their clinical potential.
      Advance in our knowledge about germ cell differentiation from stem cells will
      enable researchers to design better in vitro strategies which in turn may have
      relevance to reproductive biology and regenerative medicine.

PMID- 24568239
TI  - Enhancement of diabetic wound repair using biodegradable nanofibrous metformin
      eluting membranes: in vitro and in vivo.
AB  - This work developed biodegradable nanofibrous drug-eluting membranes that
      provided sustained release of metformin for repairing wounds associated with
      diabetes. To prepare the biodegradable membranes, poly-d-l-lactide-glycolide
      (PLGA) and metformin were first dissolved in 1,1,1,3,3,3-hexafluoro-2-propanol
      (HFIP) and were spun into nanofibrous membranes by electrospinning. An elution
      method and an HPLC assay were utilized to characterize the in vivo and in vitro
      release rates of the pharmaceuticals from the membranes. The biodegradable
      nanofibrous membranes released high concentrations of metformin for more than
      three weeks. Moreover, nanofibrous metformin-eluting PLGA membranes were more
      hydrophilic and had a greater water-containing capacity than virgin PLGA fibers.
      The membranes also improved wound healing and re-epithelialization in diabetic
      rats relative to the control. The experimental results in this work suggest that
      nanofibrous metformin-eluting membranes were functionally active in the treatment
      of diabetic wounds and very effective as accelerators in the early stage of
      healing of such wounds. 

PMID- 24568238
TI  - Effect of omega-3 fatty acid supplementation on cancer incidence, non-vascular
      death, and total mortality: a meta-analysis of randomized controlled trials.
AB  - BACKGROUND: Omega-3 fatty acids are known to prevent cardiac death. However,
      previous observational studies have suggested that omega-3 fatty acids are
      associated with cancer risk in adults. We conducted a meta-analysis based on
      randomized controlled trials to evaluate the effect of omega-3 fatty acids on the
      risk of cancer incidence, nonvascular death, and total mortality. METHODS: In
      February 2013, we performed electronic searches in PubMed, EmBase, and the
      Cochrane Library to identify randomized controlled trials on cancer incidence,
      nonvascular death, and total mortality. Relative risk (RR) was used to measure
      the effect of omega-3 fatty acid supplementation on the risk of cancer incidence,
      nonvascular death, and total mortality using a random-effect model. The analysis
      was further stratified by factors that could affect the treatment effects.
      RESULTS: Of the 8,746 identified articles, we included 19 trials reporting data
      on 68,954 individuals. These studies reported 1,039 events of cancer, 2,439
      events of nonvascular death, and 7,025 events of total mortality. Omega-3 fatty
      acid supplementation had no effect on cancer incidence (RR, 1.10; 95% CI: 0.97
      1.24; P = 0.12), nonvascular death (RR, 1.00; 95% CI: 0.93-1.08; P = 1.00), or
      total mortality (RR, 0.95; 95% CI: 0.88-1.03; P = 0.24) when compared to a
      placebo. Subgroup analysis indicated that omega-3 fatty acid supplementation was
      associated with a reduction in total mortality risk if the proportion of men in
      the study population was more than 80%, or participants received alpha-linolenic
      acid. CONCLUSIONS: Omega-3 fatty acid supplementation does not have an effect on
      cancer incidence, nonvascular death, or total mortality.

PMID- 24568240
TI  - Nicotinic acid and its derivatives: synthetic routes, crystal forms and
      polymorphs.
AB  - Nicotinic acid is a well-known pharmaceutical in the vitamin B group that has
      attracted great interest in the past decades due to its significant importance in
      the treatment of the human diseases like pellagra. Also, nicotinic acid
      derivatives have been devoted to much attention due to their different
      pharmaceutical effects in the treatment of diseases. In view of this, the
      developments of nicotinic acid and its derivatives including their synthetic
      methods by using different substrates, and their structural modifications (e.g.,
      substitution of one or more positions of pyridyl ring or acid) were reviewed in
      details. Drug molecules like nicotinic acid and its derivatives may exist in more
      than one crystal form in its solid state, known as polymorphs. Different
      polymorphs have different dissolution rates and aqueous solubility. Therefore, we
      reviewed structures of different crystal forms of nicotinic acid and its
      derivatives. 

PMID- 24568241
TI  - Mechanism of graphene oxide formation.
AB  - Despite intensive research, the mechanism of graphene oxide (GO) formation
      remains unclear. The role of interfacial interactions between solid graphite and
      the liquid reaction medium, and transport of the oxidizing agent into the
      graphite, has not been well-addressed. In this work, we show that formation of GO
      from graphite constitutes three distinct independent steps. The reaction can be
      stopped at each step, and the corresponding intermediate products can be
      isolated, characterized, and stored under appropriate conditions. The first step
      is conversion of graphite into a stage-1 graphite intercalation compound (GIC).
      The second step is conversion of the stage-1 GIC into oxidized graphite, which we
      define as pristine graphite oxide (PGO). This step involves diffusion of the
      oxidizing agent into the preoccupied graphite galleries. This rate-determining
      step makes the entire process diffusive-controlled. The third step is conversion
      of PGO into conventional GO after exposure to water, which involves hydrolysis of
      covalent sulfates and loss of all interlayer registry. 

PMID- 24568242
TI  - The effect of HIV and antiretroviral therapy on characteristics of pulmonary
      tuberculosis in northern Malawi: a cross-sectional study.
AB  - BACKGROUND: HIV infection reduces the likelihood that individuals with pulmonary
      tuberculosis are smear positive and that they have cavitatory disease.
      Antiretroviral therapy (ART) may shift the pattern of disease to be more similar
      to that of HIV negative patients. This would aid diagnosis--which often depends
      on sputum smears--but would also increase infectiousness. We assessed the effect
      of HIV and ART on smear positivity and cavitatory disease in laboratory-confirmed
      pulmonary TB patients. METHODS: Three sputum samples were collected per pulmonary
      TB suspect and were examined using microscopy and culture. Chest radiographs were
      available for a subset of patients as part of another study. The effect of HIV
      and ART status on sputum smear positivity and lung cavitation were evaluated
      using multivariable logistic regression. RESULTS: Of 1024 laboratory-confirmed
      pulmonary TB patients who were identified between January 2005 and December 2011,
      766 had HIV and ART status available. Positive sputum smears were significantly
      more common among HIV negative individuals than HIV positive individuals
      (adjusted OR = 2.91, 95% CI 1.53-5.55). Compared to those HIV positive but not on
      ART, patients on ART were more likely to be smear positive (adjusted OR = 2.33,
      95% CI 1.01-5.39) if they had been on ART <= 6 months, but only slightly more
      likely to be smear positive (adjusted OR = 1.43, 95% CI 0.68-2.99) if they were
      on ART > 6 months. HIV negative patients were more likely than HIV positive
      patients to have cavitatory disease (adjusted OR = 1.97, 95% CI 1.20-3.23).
      Patients on ART > 6 months had a slight increase in cavitatory disease compared
      to HIV positive patients not on ART (adjusted OR = 1.68, CI 0.78-3.63).
      CONCLUSIONS: HIV infection is associated with less smear positivity and
      cavitation in pulmonary TB patients. Among HIV positive patients, the use of ART
      shifts the presentation of disease towards that seen in HIV-negative individuals,
      which facilitates diagnosis but which also could increase infectiousness.

PMID- 24568243
TI  - A QM/MM study of the L-threonine formation reaction of threonine synthase:
      implications into the mechanism of the reaction specificity.
AB  - Threonine synthase catalyzes the most complex reaction among the pyridoxal-5'
      phosphate (PLP)-dependent enzymes. The important step is the addition of a water
      molecule to the Cbeta-Calpha double bond of the PLP-alpha-aminocrotonate aldimine
      intermediate. Transaldimination of this intermediate with Lys61 as a side
      reaction to form alpha-ketobutyrate competes with the normal addition reaction.
      We previously found that the phosphate ion released from the O-phospho-l
      homoserine substrate plays a critical role in specifically promoting the normal
      reaction. In order to elucidate the detailed mechanism of this "product-assisted
      catalysis", we performed comparative QM/MM calculations with an exhaustive search
      for the lowest-energy-barrier reaction pathways starting from PLP-alpha
      aminocrotonate aldimine intermediate. Satisfactory agreements with the experiment
      were obtained for the free energy profile and the UV/vis spectra when the PLP
      pyridine N1 was unprotonated and the phosphate ion was monoprotonated. Contrary
      to an earlier proposal, the base that abstracts a proton from the attacking water
      was the epsilon-amino group of Lys61 rather than the phosphate ion. Nevertheless,
      the phosphate ion is important for stabilizing the transition state of the normal
      transaldimination to form l-threonine by making a hydrogen bond with the hydroxy
      group of the l-threonine moiety. The absence of this interaction may account for
      the higher energy barrier of the side reaction, and explains the mechanism of the
      reaction specificity afforded by the phosphate ion product. Additionally, a new
      mechanism, in which a proton temporarily resides at the phenolate O3' of PLP, was
      proposed for the transaldimination process, a prerequisite step for the catalysis
      of all the PLP enzymes. 

PMID- 24568244
TI  - Red cell distribution width: a novel and simple predictor of mortality in chronic
      obstructive pulmonary disease.

PMID- 24568246
TI  - Toward salivary gland stem cell regeneration.
AB  - Head and neck cancer is the sixth most common cancer worldwide, resulting in ~
      640,000 cases. Most of these patients have irreversible damage to their salivary
      glands due to irradiation therapy, which typically leads to significant decrease
      in quality of life. In the last 2 decades, several strategies have been suggested
      to overcome this problem; however, no biologically based treatments are
      available. In the past few years, the authors of the present article and other
      researchers have focused on a new strategy of re-implantation of autologous
      salivary gland cells into the residual irradiated salivary glands. This article
      reviews the current prospective of the irradiation-induced salivary gland
      impairment mechanisms and the envisioned therapeutic modalities based on stem
      cell therapy. 

PMID- 24568245
TI  - Orthodontic-associated localized gingival recession of lower incisors: who should
      treat it?
AB  - Gingival recession of lower incisors in the young population has become more
      prevalent in association with the increased uptake of orthodontic treatment. The
      two main predisposing factors are thin gingival biotype and bone dehiscence
      caused by labially displaced roots. Management is sometimes challenging, and the
      achievement of a successful result requires close cooperation between the
      orthodontist and periodontist. This article proposes a decision tree, which
      includes both orthodontic and periodontal considerations, to help the clinician
      in making the correct diagnosis and choosing the most suitable treatment in post
      orthodontic gingival recessions. 

PMID- 24568247
TI  - From maximally to minimally invasive surgery for sinus floor augmentation.
AB  - Placing implants in the posterior region of the maxilla may require expanding the
      floor of the maxillary sinus. A major surgical procedure developed 30 years ago
      used lateral window access to the sinus cavity to achieve this. In the
      intervening years, less invasive techniques using a crestal approach were
      introduced; while they have reduced the complication and morbidity risks, they
      require micro-surgical skills. This review of the progression of maxillary sinus
      augmentation from major surgery to a minimally invasive procedure explores the
      various surgical approaches, discussing the advantages and disadvantages of each.

PMID- 24568248
TI  - Existing concepts and a search for evidence: a review on implant occlusion.
AB  - The prevalence of dental implant treatment raises the question: What factors may
      challenge osseointegration? The dental literature presents two main approaches,
      which are well-documented: loss of bone around the implant due to infection and a
      presumed association between implant load and bone loss. This article discusses
      the effect of load or overload on the bone loss around dental implants. The
      dental literature is reviewed to assess the scientific evidence related to the
      effect of occlusal load on osseointegration. Recommendations found in the
      literature for occlusal schemes for implant-supported prostheses are examined and
      discussed, and statements regarding implant occlusion are assessed for their
      validity today, after more than four decades of implants service in prosthetic
      dentistry. 

PMID- 24568250
TI  - Metabolic status of pluripotent cells and exploitation for growth in stirred
      suspension bioreactors.
AB  - Pluripotent stem cells are of great interest in the field of regenerative
      medicine. Recent studies have shown that they maintain a glycolytic metabolic
      status while pluripotent and wholesale changes to mitochondrial and metabolic
      profile occur during differentiation. This article reviews the process and how
      this may be exploited in a stirred suspension bioreactor for rapid growth while
      maintaining pluripotency. 

PMID- 24568249
TI  - Fitness, nutrition and the molecular basis of chronic disease.
AB  - The onset of chronic disease is often the prelude to the subsequent physiological
      and mental twilight in the aging population of modern society. While rates of
      obesity, specific types of cancer and cardiovascular disorders seem to be on the
      rise in this group, many new therapies have addressed diseases that have been
      largely untreatable in the past. Alzheimer's disease has also recently come to
      the forefront of ongoing maladies most typically associated with an aging
      population. Ironically, though, many people seem to be living longer than
      expected. Recent biochemical, nutritional and genomic approaches have been able
      to elucidate some of the complex mechanisms, which lead to chronic diseases
      associated with an aging population such as Alzheimer's, metabolic syndrome,
      tumor metastasis and cardiovascular disease. These diseases and their sequalae
      seem to be related in many respects, with the common culprit being the
      inflammatory environment created by the presence of excess fat - particularly
      within the vascular network. Although a substantial effort has been focused on
      the development of new-line therapeutics to address these issues, nutrition and
      overall fitness and their effects on stalling or potentially reversing the advent
      of these diseases has not been fully embraced in the research arena. This review
      discusses the role of the inflammatory environment in the development of chronic
      diseases in the aging population and also proposes a common pathology. The
      benefits that improvements and dedication in nutrition and fitness approaches may
      offer at the molecular level are also discussed. 

PMID- 24568251
TI  - G-protein-coupled receptor regulation of de novo purine biosynthesis: a novel
      druggable mechanism.
AB  - Spatial organization of metabolic enzymes may represent a general cellular
      mechanism to regulate metabolic flux. One recent example of this type of cellular
      phenomenon is the purinosome, a newly discovered multi-enzyme metabolic assembly
      that includes all of the enzymes within the de novo purine biosynthetic pathway.
      Our understanding of the components and regulation of purinosomes has
      significantly grown in recent years. This paper reviews the purine de novo
      biosynthesis pathway and its regulation, and presents the evidence supporting the
      purinosome assembly and disassembly processes under the control of G-protein
      coupled receptor (GPCR) signaling. This paper also discusses the implications of
      purinosome and GPCR regulation in drug discovery.

PMID- 24568252
TI  - Post-transcriptional regulation of cytokine mRNA controls the initiation and
      resolution of inflammation.
AB  - Cytokines are critical mediators of inflammation and host defense. Cytokine
      production is regulated during transcription and post-transcription. Post
      transcriptional regulation modifies mRNA stability and translation, allowing for
      the rapid and flexible control of gene expression, which is important for
      coordinating the initiation and resolution of inflammation. We review here a
      variety of post-transcriptional control mechanisms that regulate inflammation and
      discuss how these mechanisms are integrated to coordinate this essential process.

PMID- 24568253
TI  - Nanogel-based antigen-delivery system for nasal vaccines.
AB  - Nasal vaccination is considered a potent and practical immunization route for the
      induction of effective immunity to infectious diseases. Successful nasal vaccines
      require efficient delivery to, and retention of antigens within, nasal mucosa,
      including both the inductive (e.g., nasopharynx-associated lymphoid tissues) and
      effector (e.g., turbinate covered with single-layer epithelium) tissues, where
      antigen-specific immune responses are initiated and executed, respectively. We
      developed an approach towards successful nasal vaccination by using self
      assembled nano-sized hydrogel particles, known as nanogels, which are composed of
      a cationic type of cholesteryl group-bearing pullulan. Here, we review the
      merging of nanotechnological and immunological concepts leading to the
      development of next-generation nasal vaccines, and demonstrate the applicability
      of novel nanogel-based vaccine for the prevention of infectious diseases.

PMID- 24568255
TI  - Stability of complex carbohydrate structures: Biofuels, foods, vaccines and
      shipwrecks.

PMID- 24568256
TI  - Synthesis and antimicrobial evaluation of novel bis-beta-lactam grafted
      macrocycles.
AB  - A series of macrocyclic bis-beta-lactams has been synthesized in three good
      yielding steps using a Staudinger [2+2] cycloaddition reaction of ketene derived
      from phenoxyacetyl chloride as the key step. The reaction provided a
      diastereomeric mixture of cis-anti-cis (C2-symmetry) and cis-syn-cis (meso) bis
      beta-lactam grafted macrocycles which were screened for their in vitro
      antibacterial and antifungal activities against four human pathogenic bacteria
      and two pathogenic fungi. Compounds 6a and 6b exhibited antibacterial activity at
      lower concentration against four bacterial pathogens and compounds 10b and 12a
      showed antifungal activity against two fungal pathogens when compared to
      reference control. 

PMID- 24568257
TI  - Adult-acquired flatfoot deformity and age-related differences in foot and ankle
      kinematics during the single-limb heel-rise test.
AB  - STUDY DESIGN: Cross-sectional laboratory study. OBJECTIVE: To compare single-limb
      heel-rise performance and foot-ankle kinematics between persons with stage 2
      adult-acquired flat foot deformity (AAFD) and healthy controls. BACKGROUND: The
      inability to perform a single-limb heel rise is considered a positive functional
      diagnostic test for AAFD. However, which foot motions contribute to poor
      performance of this task are not known. METHODS: Fifty individuals participated
      in this study, 20 with stage 2 AAFD (mean +/- SD age, 57.6 +/- 11.3 years), and
      15 older participants (age, 56.8 +/- 5.3 years) and 15 younger participants (age,
      22.2 +/- 2.4 years) without AAFD as control groups. Forefoot (sagittal plane) and
      rear foot (sagittal and frontal planes) kinematics were collected using a 3-D
      motion analysis system. Heel-rise performance (heel height) and kinematics (joint
      angles, excursions) were evaluated. One-way and 2-way analyses of variance were
      used to examine differences in heel-rise performance and kinematics between
      groups. RESULTS: Individuals with AAFD and older controls demonstrated lower heel
      rise height than those in the younger control group (P<.001). Persons with AAFD
      demonstrated higher degrees of first metatarsal dorsiflexion (P<.001), lower
      ankle plantar flexion (P<.001), and higher subtalar eversion (P = .027) than
      those in the older control group. Persons with AAFD demonstrated lower ankle
      excursion (P<.001) and first metatarsal excursion (P<.001) than those in the
      older control group, but no difference in subtalar excursion (P = .771).
      CONCLUSION: Persons with stage 2 AAFD did not achieve sufficient heel height
      during a single-leg heel rise. Both forefoot and rear foot kinematics in the
      sagittal plane, as opposed to the frontal plane, contributed to the lower heel
      height in participants with stage 2 AAFD. Older controls demonstrated lower heel
      rise height than younger controls, indicating that clinical expectations of heel
      rise performance may need to be adjusted for age.

PMID- 24568258
TI  - Effects of functional stabilization training on pain, function, and lower
      extremity biomechanics in women with patellofemoral pain: a randomized clinical
      trial.
AB  - STUDY DESIGN: Randomized clinical trial. OBJECTIVES: To compare the effects of
      functional stabilization training (FST) versus standard training on knee pain and
      function, lower-limb and trunk kinematics, trunk muscle endurance, and eccentric
      hip and knee muscle strength in women with patellofemoral pain. BACKGROUND: A
      combination of hip- and knee-strengthening exercise may be more beneficial than
      quadriceps strengthening alone to improve pain and function in individuals with
      patellofemoral pain. However, there is limited evidence of the effectiveness of
      these exercise programs on the biomechanics of the lower extremity. METHODS:
      Thirty-one women were randomized to either the FST group or standard-training
      group. Patients attended a baseline assessment session, followed by an 8-week
      intervention, and were reassessed at the end of the intervention and at 3 months
      after the intervention. Assessment measures were a 10-cm visual analog scale for
      pain, the Lower Extremity Functional Scale, and the single-leg triple-hop test. A
      global rating of change scale was used to measure perceived improvement.
      Kinematics were assessed during the single-leg squat. Outcome measures also
      included trunk endurance and eccentric hip and knee muscle strength assessment.
      RESULTS: The patients in the FST group had less pain at the 3-month follow-up and
      greater global improvement and physical function at the end of the intervention
      compared to those in the standard-training group. Lesser ipsilateral trunk
      inclination, pelvis contralateral depression, hip adduction, and knee abduction,
      along with greater pelvis anteversion and hip flexion movement excursions during
      the single-leg squat, were only observed in the FST group after the intervention.
      Only those in the FST group had greater eccentric hip abductor and knee flexor
      strength, as well as greater endurance of the anterior, posterior, and lateral
      trunk muscles, after training. CONCLUSION: An intervention program consisting of
      hip muscle strengthening and lower-limb and trunk movement control exercises was
      more beneficial in improving pain, physical function, kinematics, and muscle
      strength compared to a program of quadriceps-strengthening exercises alone.

PMID- 24568254
TI  - Proteomic identification of protein ubiquitination events.
AB  - Protein ubiquitination is an important post-translational modification that
      regulates almost every aspect of cellular function and many cell signaling
      pathways in eukaryotes. Alterations of protein ubiquitination have been linked to
      many diseases, such as cancer, neurodegenerative diseases, cardiovascular
      diseases, immunological disorders and inflammatory diseases. To understand the
      roles of protein ubiquitination in these diseases and in cell signaling pathways,
      it is necessary to identify ubiquitinated proteins and their modification sites.
      However, owing to the nature of protein ubiquitination, it is challenging to
      identify the exact modification sites under physiological conditions. Recently,
      ubiquitin-remnant profiling, an immunoprecipitation approach, which uses
      monoclonal antibodies specifically to enrich for peptides derived from the
      ubiquitinated portion of proteins and mass spectrometry for their identification,
      was developed to determine ubiquitination events from cell lysates. This approach
      has now been widely applied to profile protein ubiquitination in several cellular
      contexts. In this review, we discuss mass-spectrometry-based methods for the
      identification of protein ubiquitination sites, analyze their advantages and
      disadvantages, and discuss their application for proteomic analysis of
      ubiquitination. 

PMID- 24568259
TI  - Knee extension and stiffness in osteoarthritic and normal knees: a
      videofluoroscopic analysis of the effect of a single session of manual therapy.
AB  - STUDY DESIGN: Descriptive biomechanical study using an experimental repeated
      measures design. OBJECTIVE: To quantify the response of participants with and
      without knee osteoarthritis (OA) to a single session of manual physical therapy.
      The intervention consisted primarily of joint mobilization techniques,
      supplemented by exercises, aiming to improve knee extension. BACKGROUND: While
      manual therapy benefits patients with knee OA, there is limited research
      quantifying the effects of a manual therapy treatment session on either motion or
      stiffness of osteoarthritic and normal knees. Methods The study included 5
      participants with knee OA and 5 age-, gender-, and body mass index-matched
      healthy volunteers. Knee extension motion and stiffness were measured with
      videofluoroscopy before and after a 30-minute manual therapy treatment session.
      Analysis of variance and intraclass correlation coefficients were used to analyze
      the data. RESULTS: Participants with knee OA had restricted knee extension range
      of motion at baseline, in contrast to the participants with normal knees, who had
      full knee extension. After the therapy session, there was a significant increase
      in knee motion in participants with knee OA (P = .004) but not in those with
      normal knees (P = .201). For stiffness data, there was no main effect for time (P
      = .903) or load (P = .274), but there was a main effect of group (P = .012), with
      the participants with healthy knees having greater stiffness than those with knee
      OA. Reliability, using intraclass correlation coefficient model 3,3, for knee
      angle measurements between imaging sessions for all loading conditions was 0.99.
      Reliability (intraclass correlation coefficient model 3,1) for intraimage
      measurements was 0.97. CONCLUSION: End-range knee extension stiffness was greater
      in the participants with normal knees than those with knee OA. The combination of
      lesser stiffness and lack of motion in those with knee OA, which may indicate the
      potential for improvement, may explain why increased knee extension angle was
      observed following a single session of manual therapy in the participants with
      knee OA but not in those with normal knees. Videofluoroscopy of the knee appears
      reliable and relevant for future studies attempting to quantify the underlying
      mechanisms of manual therapy. J Orthop Sports Phys Ther 2014;44(4):273-282. Epub
      25 February 2014. doi:10.2519/jospt.2014.4710.

PMID- 24568260
TI  - Short-term changes in neck pain, widespread pressure pain sensitivity, and
      cervical range of motion after the application of trigger point dry needling in
      patients with acute mechanical neck pain: a randomized clinical trial.
AB  - STUDY DESIGN: Randomized clinical trial. OBJECTIVES: To determine the effects of
      trigger point dry needling (TrPDN) on neck pain, widespread pressure pain
      sensitivity, and cervical range of motion in patients with acute mechanical neck
      pain and active trigger points in the upper trapezius muscle. BACKGROUND: TrPDN
      seems to be effective for decreasing pain in individuals with upper-quadrant pain
      syndromes. Potential effects of TrPDN for decreasing pain and sensitization in
      individuals with acute mechanical neck pain are needed. Methods Seventeen
      patients (53% female) were randomly assigned to 1 of 2 groups: a single session
      of TrPDN or no intervention (waiting list). Pressure pain thresholds over the C5
      6 zygapophyseal joint, second metacarpal, and tibialis anterior muscle; neck pain
      intensity; and cervical spine range-of-motion data were collected at baseline
      (pretreatment) and 10 minutes and 1 week after the intervention by an assessor
      blinded to the treatment allocation of the patient. Mixed-model analyses of
      variance were used to examine the effects of treatment on each outcome variable.
      RESULTS: Patients treated with 1 session of TrPDN experienced greater decreases
      in neck pain, greater increases in pressure pain threshold, and higher increases
      in cervical range of motion than those who did not receive an intervention at
      both 10 minutes and 1 week after the intervention (P<.01 for all comparisons).
      Between-group effect sizes were medium to large immediately after the TrPDN
      session (standardized mean score differences greater than 0.56) and large at the
      1-week follow-up (standardized mean score differences greater than 1.34).
      CONCLUSION: The results of the current randomized clinical trial suggest that a
      single session of TrPDN may decrease neck pain intensity and widespread pressure
      pain sensitivity, and also increase active cervical range of motion, in patients
      with acute mechanical neck pain. Changes in pain, pressure pain threshold, and
      cervical range of motion surpassed their respective minimal detectable change
      values, supporting clinically relevant treatment effects. Level of Evidence
      Therapy, level 1b-.

PMID- 24568261
TI  - Microfluidic approach to the formation of internally porous polymer particles by
      solvent extraction.
AB  - We report the controlled formation of internally porous polyelectrolyte particles
      with diameters ranging from tens to hundreds of micrometers through selective
      solvent extraction using microfluidics. Solvent-resistant microdevices,
      fabricated by frontal photopolymerization, encapsulate binary polymer (P)/solvent
      (S1) mixtures by a carrier solvent phase (C) to form plugs with well-defined
      radii and low polydispersity; the suspension is then brought into contact with a
      selective extraction solvent (S2) that is miscible with C and S1 but not P,
      leading to the extraction of S1 from the droplets. The ensuing phase inversion
      yields polymer capsules with a smooth surface but highly porous internal
      structure. Depending on the liquid extraction time scale, this stage can be
      carried out in situ, within the chip, or ex situ, in an external S2 bath. Bimodal
      polymer plugs are achieved using asymmetrically inverted T junctions. For this
      demonstration, we form sodium poly(styrenesulfonate) (P) particles using water
      (S1), hexadecane (C), and methyl ethyl ketone (S2). We measure droplet extraction
      rates as a function of drop size and polymer concentration and propose a simple
      scaling model to guide particle formation. We find that the extraction time
      required to form particles from liquid droplets does not depend on the initial
      polymer concentration but is rather proportional to the initial droplet size. The
      resulting particle size follows a linear relationship with the initial droplet
      size for all polymer concentrations, allowing for the precise control of particle
      size. The internal particle porous structure exhibits a polymer density gradient
      ranging from a dense surface skin toward an essentially hollow core. Average
      particle porosities between 10 and 50% are achieved by varying the initial
      droplet compositions up to 15 wt % polymer. Such particles have potential
      applications in functional, optical, and coating materials. 

PMID- 24568262
TI  - Changes in microtubule-related proteins and autophagy in long-term vitamin E
      deficient mice.
AB  - Vitamin E deficiency induces neuronal dysfunction and while oxidative stress is
      likely to be involved in mediating this process, the detailed mechanisms remain
      to be elucidated. Previously, we found axonal degeneration in the hippocampal CA1
      region in vitamin E-deficient mice of 6 months of age (long-term). However, 3
      month-old (short-term) vitamin E-deficient mice did not exhibit axonal
      degeneration in same region. In order to characterize the mechanisms involved in
      axonal degeneration in long-term vitamin E-deficient mice, we examined changes in
      microtubule-related proteins. Long-term vitamin E-deficiency led to significantly
      increased expression of the phosphorylated form of collapsin response mediator
      protein (CRMP)-2 compared to short-term deficiency. It is well known that CRMP-2
      plays a crucial role in the maintenance of neurite function. Similarly, long-term
      vitamin E-deficiency significantly decreased the expression of silent mating type
      information regulation (SIRT)-2 mRNA compared to short-term deficiency. SIRT-2
      belongs to a family of class III histone deacetylases (HDACs) and functions in
      the deacetylation of tubulins. Furthermore, the expression of microtubule
      associated protein light chain (MAP-LC)3-2, which is a key autophagy protein was
      significantly higher in the short-term vitamin E-deficiency than the long-term
      deficiency. These results indicate that the mechanisms of axonal injury in long
      term vitamin E-deficient mice are related to dysfunction in microtubules assembly
      via alterations in microtubule-related proteins and autophagy.

PMID- 24568265
TI  - Solubility of poly(methyl methacrylate) in ionic liquids in relation to solvent
      parameters.
AB  - The solubility of poly(methyl methacrylate) (PMMA) in 1-alkyl-3-methylimidazolium
      ionic liquids (ILs) with different anionic structures has been explored. Nearly
      monodisperse PMMA-grafted silica nanoparticles (PMMA-g-NPs) were used as a
      measurement probe for evaluating the PMMA solubility in ILs. The hydrodynamic
      radius (Rh) of PMMA-g-NPs was measured in the ILs by dynamic light scattering
      (DLS). Changes in Rh and colloidal stability, that is, the PMMA-solubility change
      in the ILs, were observed depending on the ionic structures of the ILs. The
      solubility was mainly affected by the anionic structures of the ILs rather than
      by the alkyl chain length of the cationic structure. Solvent parameters,
      including Lewis basicity, solubility parameters, and a hydrophobicity parameter,
      were used to discuss the change in the PMMA solubility in ILs with different
      ionic structures. By considering the PMMA solubility in the ILs using these
      parameters, it was found that there is a good correlation between the PMMA
      solubility and the hydrophobicity parameter of the anions. Although the change in
      the PMMA solubility with different cationic structures was not remarkable, the
      hydrophobicity of the cations also played a role in the solvation of PMMA by
      providing a low-polarity environment adequate to dissolve PMMA. 

PMID- 24568264
TI  - Expression and prognostic significance of the polymeric immunoglobulin receptor
      in epithelial ovarian cancer.
AB  - BACKGROUND: High expression of the polymeric immunoglobulin receptor (PIGR) has
      previously been associated with a favourable prognosis in a few cancer forms, but
      its expression and relationship with clinical outcome in epithelial ovarian
      cancer (EOC) has not yet been reported. The aim of this study was therefore to
      examine the clinicopathological correlates and prognostic significance of PIGR
      expression in EOC. METHODS: After an initial screening in the Human Protein Atlas
      portal, a validated antibody was selected for extended analysis of
      immunohistochemical PIGR expression in tissue microarrays with tumours from 154
      incident cases of EOC from two pooled prospective population-based cohorts.
      Subsets of corresponding benign-appearing fallopian tubes (n = 38) and omental
      metastases (n = 33) were also analysed. Kaplan-Meier analysis and Cox regression
      analysis were applied to examine the impact of PIGR expression on overall
      survival (OS) and ovarian cancer-specific survival (OCSS). RESULTS: PIGR
      expression was significantly higher in fallopian tubes compared to primary
      tumours and metastases (p < 0.001) and lower in carcinoma of the serous subtype
      compared to other carcinomas (p < 0.001). PIGR expression was significantly
      associated with lower grade (p = 0.001), mucinous histological subtype (p =
      0.002), positive progesterone receptor expression (p = 0.009) and negative or low
      Ki-67 expression (p = 0.003). Kaplan-Meier analysis revealed a significantly
      improved OS (p = 0.013) and OCSS (p = 0.009) for patients with tumours displaying
      high expression of PIGR. These associations were confirmed in unadjusted Cox
      regression analysis (HR = 0.48; 95% CI 0.26-0.87; p = 0.015 for OS and HR = 0.43,
      95% CI 0.22-0.82; p = 0.011 for OCSS) but did not remain significant after
      adjustment for age, grade and clinical stage. CONCLUSIONS: This study provides a
      first demonstration of PIGR expression in human fallopian tubes, primary EOC
      tumours and metastases. High tumour-specific expression of PIGR was found to be
      associated with a favourable prognosis in unadjusted, but not in adjusted,
      analysis. These findings are novel and merit further investigation.

PMID- 24568266
TI  - Simulated transfer of liquids and powders from hands and clothing to the mouth.
AB  - A series of laboratory experiments was carried out to assess transfer of liquids
      (vinegar) and powders (calcium acetate and magnesium carbonate) from hands, arms,
      gloves, respirators, clothing, and pens to the oral cavity or the perioral area
      (the area surrounding the mouth). Experiments were carried out with four
      volunteers. The donor area (the hands, arms, gloves, and so on) was loaded with a
      known mass of the test substance and was then brought into contact the receiver
      area (the oral cavity or the perioral area). The percentage of the substance on
      the donor that transferred to the receiver (the transfer efficiency or TE) was
      assessed using saliva samples and gauze wipes of the perioral area. Magnesium
      carbonate was measured on gauze and in saliva using inductively coupled
      plasma/atomic emission spectrometry. Calcium acetate and vinegar were measured
      using ion chromatography/electrochemical detection. Average transfer efficiencies
      were calculated for each substance and transfer scenario; these were compared
      using ANOVA and Kruskal-Wallis tests. Overall, direct transfer from the hands to
      the oral cavity was significantly higher (mean TE = 51.6) than indirect transfer
      from the hands to the oral cavity via the perioral area by licking the lips (mean
      TE = 11.5). The results suggested higher TEs for liquids than for solids and that
      hand-to-mouth TEs may increase with water solubility. Transfer from bare arms to
      the perioral area was higher than from arms covered by cotton sleeves for both
      liquids and powders. Although TE data are often required by models estimating
      exposure by inadvertent ingestion, relatively few published data are available.
      This study has provided evidence of some factors that may influence transfer of
      chemicals from hands or objects to the mouth (physical form, use of clothing, and
      so on) and has provided data that are essential for the development of predictive
      exposure models of inadvertent ingestion exposure. 

PMID- 24568267
TI  - Cruciform alkynylated anthanthrene derivatives: a structure-properties
      relationship case study.
AB  - An efficient and versatile synthetic strategy toward cruciform anthanthrene
      compounds using Sonogashira couplings steps was developed. Acetylenic linkers
      were used to effectively extend the pi-conjugation of polycyclic anthanthrone and
      anthanthrene compounds and tune their optoelectronic properties. Structure
      property relationships supported by DFT calculations indicated more effective pi
      conjugation along the 6,12 axis than along the 4,10 axis. These molecules
      displayed strong J-aggregation both in solution and in the solid state and proved
      to be highly photostable with reversible redox processes, which are properties of
      interest in materials sciences. 

PMID- 24568268
TI  - Electrochemically directed synthesis of Cu2(I)(TCNQF4(II-))(MeCN)2 (TCNQF4 =
      2,3,5,6-tetrafluoro-7,7,8,8-tetracyanoquinodimethane): voltammetry, simulations,
      bulk electrolysis, spectroscopy, photoactivity, and X-ray crystal structure of
      the Cu2(I)(TCNQF4(II-))(EtCN)2 analogue.
AB  - The new compound Cu2(I)(TCNQF4(II-))(MeCN)2 (TCNQF4(2-) = dianion of 2,3,5,6
      tetrafluoro-7,7,8,8-tetracyanoquinodimethane) has been synthesized by
      electrochemically directed synthesis involving reduction of TCNQF4 to TCNQF4(2-)
      in acetonitrile containing [Cu(MeCN)4](+)(MeCN) and 0.1 M Bu4NPF6. In one
      scenario, TCNQF4(2-) is quantitatively formed by reductive electrolysis of TCNQF4
      followed by addition of [Cu(MeCN)4](+) to form the Cu2(I)(TCNQF4(II-))(MeCN)2
      coordination polymer. In a second scenario, TCNQF4 is reduced in situ at the
      electrode surface to TCNQF4(2-), followed by reaction with the [Cu(MeCN)4](+)
      present in the solution, to electrocrystallize Cu2(I)(TCNQF4(II-))(MeCN)2. Two
      distinct phases of Cu2(I)(TCNQF4(II-))(MeCN)2 are formed in this scenario; the
      kinetically favored form being rapidly converted to the thermodynamically favored
      Cu2(I)(TCNQF4(II-))(MeCN)2. The postulated mechanism is supported by simulations.
      The known compound Cu(I)TCNQF4(I-) also has been isolated by one electron
      reduction of TCNQF4 and reaction with [Cu(MeCN)4](+). The solubility of both
      TCNQF4(2-)- and TCNQF4(*-)-derived solids indicates that the higher solubility of
      Cu(I)TCNQF4(I-) prevents its precipitation, and thus Cu2(I)(TCNQF4(II-))(MeCN)2
      is formed. UV-visible and vibrational spectroscopies were used to characterize
      the materials. Cu2(I)(TCNQF4(II-))(MeCN)2 can be photochemically transformed to
      Cu(I)TCNQF4(I-) and Cu(0). Scanning electron microscopy images reveal that
      Cu(I)TCNQF4(I-) and Cu2(I)(TCNQF4(II-))(MeCN)2 are electrocrystallized with
      distinctly different morphologies. Thermogravimetric and elemental analysis data
      confirm the presence of CH3CN, and single-crystal X-ray diffraction data for the
      Cu2(I)(TCNQF4(II-))(EtCN)2 analogue shows that this compound is structurally
      related to Cu2(I)(TCNQF4(II-))(MeCN)2. 

PMID- 24568263
TI  - Molecular subtyping of metastatic renal cell carcinoma: implications for targeted
      therapy.
AB  - BACKGROUND: Renal cell carcinoma (RCC) is known for its ability to metastasize
      synchronously or metachronously to various anatomic sites. Distinguishing
      histologic subtypes of metastatic RCC has become increasingly important, as
      prognosis and therapy can differ dramatically between subtypes. We propose a
      combination of immunohistochemistry (IHC) and molecular cytogenetics for
      subtyping metastatic RCC in light of these potential therapeutic implications.
      RESULTS: Specimens from 103 cases of metastatic RCC were retrieved, including 32
      cases originally diagnosed as metastatic clear cell renal cell carcinoma (CCRCC),
      8 as metastatic papillary renal cell carcinoma (PRCC), and 63 metastatic RCC
      without a specific subtype. Immunohistochemistry was performed with antibodies
      against cytokeratin 7 (CK7) and alpha-methylacyl-CoA racemase (AMACR). Dual color
      interphase fluorescence in situ hybridization was utilized to assess for deletion
      of chromosome 3p and trisomy of chromosomes 7 and 17 in all tumors. Chromosome 3p
      deletion was detected in 41% of all metastatic RCC specimens, and trisomy of
      chromosomes 7 and/or 17 was detected in 16%. Of metastatic CCRCC, chromosome 3p
      deletion was detected in 63%. Of metastatic PRCC, 75% showed trisomy of
      chromosomes 7 and/or 17. Of the tumors not previously classified, 6% were
      positive for CK7, and 64% were positive for AMACR; 35% showed chromosome 3p
      deletion, and 16% showed trisomy of chromosomes 7 and/or 17. Combined analysis of
      immunohistochemistry and cytogenetics enabled reclassification of 52% of these
      metastatic tumors not previously classified. CONCLUSION: Our findings support the
      utility of immunohistochemistry and cytogenetics for subtyping metastatic RCC.

PMID- 24568269
TI  - Preeclampsia - a risk factor for osteoporosis? Analysis of maternal Sclerostin
      levels and markers of bone turnover in patients with pre-eclampsia.
AB  - INTRODUCTION: The role of preeclampsia (PE) in affecting bone metabolism could
      not be clarified in the past years. Recently Sclerostin, a new marker of bone
      metabolism which is known to have an inhibitory effect on bone formation causing
      osteoporosis, was discovered. OBJECTIVE: To investigate serum levels of
      Sclerostin and markers of bone turnover in women with normotensive pregnancies
      and pregnancies complicated by PE. METHODS: In this prospective study we enrolled
      22 women with PE and 22 healthy pregnant women to observe serum levels of
      carboxyterminal propeptide of type I collagen (PICP), cross-linked carboxyl
      terminal telopeptide of the type I collagen (ICTP), calcium, phosphate, 25
      hydroxyvitamin D and parathyroid hormone. In 16 preeclamptic and 16 healthy
      pregnant women, serum Sclerostin levels were analyzed. RESULTS: Serum levels of
      Sclerostin (mean +/- standard deviation: healthy 10.5 +/- 8.1 pmol/l versus PE
      11.5 +/- 9.4 pmol/l, p = 0.768), ICTP (healthy 0.3 +/- 0.2 ng/ml versus PE 0.4 +/
      0.1 ng/ml, p = 0.462), PICP (healthy 59.9 +/- 49.9 ng/ml versus PE 89.0 +/- 62.0
      ng/ml, p = 0.094), phosphate (healthy 1.1 +/- 0.2 mmol/l versus PE 1.2 +/- 0.4
      mmol/l, p = 0.162) and parathyroid hormone (healthy 26.9 +/- 14 pg/ml versus PE
      35.3 +/- 17.6 pg/ml, p = 0.08) showed no significant differences between the
      groups. Significantly lower serum calcium (healthy 2.3 +/- 0.1 mmol/l versus PE
      2.2 +/- 0.2 mmol/l, p < 0.005) and serum 25-Hydroxyvitamin D (healthy 39.3 +/-
      16.7 nmol/l versus PE 23.9 +/- 16.9 nmol/l, p < 0.005) were observed in
      preeclamptic women. CONCLUSION: Pregnancies complicated by PE show no signs of
      high bone turnover and may not lead to a higher risk of osteoporosis in later
      life.

PMID- 24568270
TI  - Interventions designed to promote exclusive breastfeeding in high-income
      countries: a systematic review.
AB  - BACKGROUND: Worldwide, women fail to reach the recommended exclusive
      breastfeeding target of 6 months postpartum. The objective of this study was to
      present a conceptual and methodological synthesis of interventions designed to
      promote exclusive breastfeeding to 6 months in high-income countries. MATERIALS
      AND METHODS: A systematic search of leading databases was conducted for scholarly
      peer-reviewed randomized trials published between January 2000 and June 2013.
      Seventeen articles were identified as relevant; all were published in English and
      assessed exclusive breastfeeding with a follow-up period extending beyond 4
      months postpartum. Articles were analyzed for overall quality of evidence,
      regarding duration of exclusive breastfeeding, using the Grading and
      Recommendations Assessment, Development, and Evaluation approach. RESULTS: A
      significant increase in the duration of exclusive breastfeeding was found in
      eight of the 17 studies, with most interventions using supportive or educational
      approaches. Interventions in pregnancy focused on educating mothers on the
      benefits of exclusive breastfeeding. Fifteen interventions took place, at least
      in part, in the postnatal period and provided educational and emotional support
      to mothers. Of the eight successful interventions, five took part in the
      postnatal period in the mothers' own homes. The quality of the evidence for
      duration of exclusive breastfeeding was moderate. CONCLUSIONS: The most
      successful interventions were conducted in the postnatal period and over a long
      period of time; however, the findings were inconsistent. No study assessed
      intervention fidelity, and only two studies noted maternal body mass index, a
      variable known to affect exclusive breastfeeding rates. Further research is
      needed to provide a robust evidence base to inform future interventions.

PMID- 24568272
TI  - Effects of substituents and substitution positions on alkaline stability of
      imidazolium cations and their corresponding anion-exchange membranes.
AB  - Imidazolium cations with butyl groups at various substitution positions (N1-, C2
      , and N3-), 1-butyl-2,3-dimethylimidazolium ([N1-BDMIm](+)), 2-butyl-1,3
      dimethylimidazolium ([C2-BDMIm](+)), and 3-butyl-1,2-dimethylimidazolium ([N3
      BDMIm](+)), were synthesized. Quantitative (1)H NMR spectra and density
      functional theory calculation were applied to investigate the chemical stability
      of the imidazolium cations in alkaline solutions. The results suggested that the
      alkaline stability of the imidazolium cations was drastically affected by the C2
      substitution groups. The alkaline stability of imidazolium cations with various
      substitution groups at the C2-position, including 2-ethyl-1-butyl-3
      methylimidazolium ([C2-EBMIm](+)), 1,2-dibutyl-3-methylimidazolium ([C2
      BBMIm](+)), and 2-hydroxymethyl-1-butyl-3-methylimidazolium ([C2-HMBMIm](+)), was
      further studied. The butyl group substituted imidazolium cation ([C2-BBMIm](+))
      exhibited the highest alkaline stability at the elevated temperatures. The
      synthesized anion-exchange membranes based on the [C2-BBMIm](+) cation showed
      promising alkaline stability. These observations should pave the way to the
      practical application of imidazolium-based anion exchange membrane fuel cells. 

PMID- 24568271
TI  - A pilot study to evaluate the efficacy of adding a structured home visiting
      intervention to improve outcomes for high-risk families attending the Incredible
      Years Parent Programme: study protocol for a randomised controlled trial.
AB  - BACKGROUND: Antisocial behaviour and adult criminality often have their origins
      in childhood and are best addressed early in the child's life using evidence
      based treatments such as the 'Incredible Years Parent Programme'. However,
      families with additional risk factors who are at highest risk for poor outcomes
      do not always make sufficient change while attending such programmes. Additional
      support to address barriers and improve implementation of positive parenting
      strategies while these families attend the Incredible Years Programme may improve
      overall outcomes.The study aims to evaluate the efficacy of adding a structured
      home visiting intervention (Home Parent Support) to improve outcomes in families
      most at risk of poor treatment response from the Incredible Years intervention.
      This study will inform the design of a larger prospective randomised controlled
      trial. METHODS/DESIGN: A pilot single-blind, parallel, superiority, randomised
      controlled trial. Randomisation will be undertaken using a computer-generated
      sequence in a 1:1 ratio to the two treatments arranged in permuted blocks with
      stratification by age, sex, and ethnicity. One hundred and twenty six
      participants enrolled in the Incredible Years Parent Programme who meet the high
      risk criteria will be randomly allocated to receive either Incredible Years
      Parent Programme and Home Parent Support, or the Incredible Years Parent
      Programme alone. The Home Parent Support is a 10-session structured home visiting
      intervention provided by a trained therapist, alongside the usual Incredible
      Years Parent Programme, to enhance the adoption of key parenting skills. The
      primary outcome is the change in child behaviour from baseline to post
      intervention in parent reported Eyberg Child Behavior Inventory Problem Scale.
      DISCUSSION: This is the first formal evaluation of adding Home Parent Support
      alongside Incredible Years Parent Programme for families with risk factors who
      typically have poorer treatment outcomes. We anticipate that the intervention
      will help vulnerable families stay engaged, strengthen the adoption of effective
      parenting strategies, and improve outcomes for both the children and families.
      TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry
      ACTRN12612000878875.

PMID- 24568273
TI  - Diagnostic confusion in periorbital necrotising soft tissue infections.

PMID- 24568274
TI  - Monatomic chemical-vapor-deposited graphene membranes bridge a half-millimeter
      scale gap.
AB  - One of the main concerns in nanotechnology is the utilization of nanomaterials in
      macroscopic applications without losing their extreme properties. In an effort to
      bridge the gap between the nano- and macroscales, we propose a clever fabrication
      method, the inverted floating method (IFM), for preparing freestanding chemical
      vapor-deposited (CVD) graphene membranes. These freestanding membranes were then
      successfully suspended over a gap a half-millimeter in diameter. To understand
      the working principle of IFM, high-speed photography and white light
      interferometry were used to characterize and analyze the deformation behaviors of
      the freestanding graphene membranes in contact with a liquid during fabrication.
      Some nanoscale configurations in the macroscopic graphene membranes were able to
      be characterized by simple optical microscopy. The proposed IFM is a powerful
      approach to investigating the macroscopic structures of CVD graphene and enables
      the exploitation of freestanding CVD graphene for device applications. 

PMID- 24568276
TI  - Microfabricated nerve-electrode interfaces in neural prosthetics and neural
      engineering.
AB  - Neural interfaces and implants are finding more clinical applications and there
      are rapid technological advances for more efficient and safe design, fabrication
      and materials to establish high-fidelity neural interfaces. In this review paper,
      we highlight new developments of the microfabricated electrodes and substrates
      with regard to the design, materials, fabrication and their clinical
      applications. There is a noticeable trend towards integration of microfluidic
      modules on a single neural platform. In addition to the microelectrodes for
      neural recording and stimulation, microfluidic channels are integrated into a
      nerve-electrode interface to explore the rich neurochemistry present at the
      neural interface and exploit it for enhanced electrochemical stimulation and
      recording of the central and peripheral nervous system. 

PMID- 24568277
TI  - Metabolic engineering of plants for artemisinin synthesis.
AB  - Artemisinin, a natural compound from Artemisia annua, is highly effective in
      treating drug-resistant malaria. Because chemical synthesis of this natural
      terpenoid is not economically feasible, its only source remains as the native
      plant which produces only small quantities of it, resulting in a supply that is
      far short of demand. Extensive efforts have been invested in metabolic
      engineering for the biosynthesis of artemisinin precursors in microbes. However,
      the production of artemisinin itself has only been achieved in plants. Since, A.
      annua possesses only poorly developed genetic resources for traditional breeders,
      molecular breeding is the best alternative. In this review, we describe the
      efforts taken to enhance artemisinin production in A. annua via transgenesis and
      advocate metabolic engineering of the complete functional artemisinin metabolic
      pathway in heterologous plants. In both cases, we emphasize the need to apply
      state-of-the-art synthetic biology approaches to ensure successful biosynthesis
      of the drug. 

PMID- 24568278
TI  - Bioengineering heterodimeric cytokines: turning promiscuous proteins into
      therapeutic agents.
AB  - The interleukin 12 (IL-12) family comprises a group of heterodimeric cytokines
      that can cope with a great variety of immune conditions as the microenvironment
      demands. By sharing cytokine and receptor subunits, IL-12 (comprised of p40/p35
      subunits), IL-23 (p40/p19), IL-27 (p28/EBI3), and IL-35 (p35/EBI3) represent, as
      a whole, a highly versatile system participating in controlling the continuum
      from inflammation to tolerance. Promiscuity, a peculiar feature of those
      cytokines, is a powerful and economic means of producing individual factors with
      distinct activities via different combinations of a single set of subunits.
      Whereas IL-12 and IL-23 have a clearly dominant immunostimulatory functional
      profile and IL-35 is a potent immunosuppressive agent, IL-27 can exert both
      adjuvant and regulatory effects, depending on the cytokine milieu. Promiscuity
      itself, however, may significantly hamper the therapeutic use of heterodimeric
      cytokines. The subunits of a recombinant cytokine, when administered in its
      native form, will rapidly dissociate in vivo and reassociate with alternative
      partners, thus generating different heterodimeric or even homodimeric molecules
      (i.e., p40/p40) with unwanted effects. As in other areas, bioengineering has
      provided a formidable tool to overcome the constraints associated with the
      potential use of IL-12 family cytokines. The generation of several gene
      constructs expressing IL-12, IL-23, IL-27, IL-35, or even the homodimer p40/p40,
      in their monomerized, single-chain form has allowed us to unveil the efficacy of
      those molecules in several experimental settings, including neoplasia, viral
      infection, chronic inflammation, allergy and autoimmunity. Although work is still
      needed to obtain an overall picture of therapeutic vs. adverse effects of
      individual molecules before any use in humans, the new frontiers of
      bioengineering are now driving the production of completely new combinations of
      cytokine subunits that may further extend the potential clinical use of such
      eclectic proteins.

PMID- 24568275
TI  - CD4 T cell activation by B cells in human Leishmania (Viannia) infection.
AB  - BACKGROUND: An effective adaptive immune response requires activation of specific
      CD4 T cells. The capacity of B cells to activate CD4 T cells in human cutaneous
      leishmaniasis caused by Leishmania (Viannia) has not been evaluated. METHODS: CD4
      T cell activation by B cells of cutaneous leishmaniasis patients was evaluated by
      culture of PBMCs or purified B cells and CD4 T cells with Leishmania panamensis
      antigens. CD4 T cell and B cell activation markers were evaluated by flow
      cytometry and 13 cytokines were measured in supernatants with a bead-based
      capture assay. The effect of Leishmania antigens on BCR-mediated endocytosis of
      ovalbumin was evaluated in the Ramos human B cell line by targeting the antigen
      with anti-IgM-biotin and anti-biotin-ovalbumin-FITC. RESULTS: Culture of PBMCs
      from cutaneous leishmaniasis patients with Leishmania antigens resulted in
      upregulation of the activation markers CD25 and CD69 as well as increased
      frequency of CD25hiCD127- cells among CD4 T cells. Concomitantly, B cells
      upregulated the costimulatory molecule CD86. These changes were not observed in
      PBMCs from healthy subjects, indicating participation of Leishmania-specific
      lymphocytes expanded in vivo. Purified B cells from these patients, when
      interacting with purified CD4 T cells and Leishmania antigens, were capable of
      inducing significant increases in CD25 and CD69 expression and CD25hiCD127-
      frequency in CD4 T cells. These changes were associated with upregulation of CD86
      in B cells. Comparison of changes in CD4 T cell activation parameters between
      PBMC and B cell/CD4 T cell cultures showed no statistically significant
      differences; further, significant secretion of IFN-gamma, TNF-alpha, IL-6 and IL
      13 was induced in both types of cultures. Additionally, culture with Leishmania
      antigens enhanced BCR-mediated endocytosis of ovalbumin in Ramos human B cells.
      CONCLUSIONS: The capacity of B cells specific for Leishmania antigens in
      peripheral blood of cutaneous leishmaniasis patients to activate CD4 T cells and
      induce cytokine secretion is similar to that of all cell populations present in
      PBMCs. This capacity implicates B cells as a plausible target for modulation of
      the immune response to Leishmania infection as a therapeutic strategy.

PMID- 24568279
TI  - Antibody humanization methods - a review and update.
AB  - This article reviews recent advances achieved during recent years on various
      aspects of antibody humanization theories and techniques. Common methods for
      producing humanized antibodies including framework-homology-based humanization,
      germline humanization, complementary determining regions (CDR)-homology-based
      humanization and specificity determining residues (SDR) grafting, as well as
      advantages and disadvantages of each of these methods and their applications are
      discussed. 

PMID- 24568280
TI  - Zebrafish as a model for systems biology.
AB  - Zebrafish offer a unique vertebrate model for research areas such as drug
      development, disease modeling and other biological exploration. There is
      significant conservation of genetics and other cellular networks among zebrafish
      and other vertebrate models, including humans. Here we discuss the recent work
      and efforts made in different fields of biology to explore the potential of
      zebrafish. Along with this, we also reviewed the concept of systems biology. A
      biological system is made up of a large number of components that interact in a
      huge variety of combinations. To understand completely the behavior of a system,
      it is important to know its components and interactions, and this can be achieved
      through a systems biology approach. At the end of the paper we present a concept
      of integrating zebrafish into the systems biology approach. 

PMID- 24568281
TI  - Non-viral gene therapy for bone tissue engineering.
AB  - The possibilities of using gene therapy for bone regeneration have been
      extensively investigated. Improvements in the design of new transfection agents,
      combining vectors and delivery/release systems to diminish cytotoxicity and
      increase transfection efficiencies have led to several successful in vitro, ex
      vivo and in vivo strategies. These include growth factor or short interfering
      ribonucleic acid (siRNA) delivery, or even enzyme replacement therapies, and have
      led to increased osteogenic differentiation and bone formation in vivo. These
      results provide optimism to consider use in humans with some of these gene
      delivery strategies in the near future. 

PMID- 24568282
TI  - Meal replacements and fibre supplement as a strategy for weight loss. Proprietary
      PGX(r) meal replacement and PGX(r) fibre supplement in addition to a calorie
      restricted diet to achieve weight loss in a clinical setting.
AB  - Meal replacements and viscous soluble fibre represent safe and sustainable aids
      for weight loss. Our purpose was to determine if PGX(r) meal replacements and
      PGX((r)) fibre complex in combination with a calorie-restricted diet would aid in
      weight loss in a clinical setting. Fifty-two overweight and obese participants
      (49 women, 3 men; average age 47.1 years) with a mean body mass index (BMI) of
      33.8 +/- 6.4 kg/m(2) consumed 57 g of proprietary PGX(r) meal replacement product
      at breakfast and another 57 g at lunch for 12 weeks. In addition to the meal
      replacements, they were also asked to consume 5 g/day of PGX(r) fibre in the form
      of granules, powder or capsules together with 250 mlwater. A registered dietician
      recommended low-fat, low-glycaemic-index foods for snacks and the dinner menus
      such that each volunteer was consuming a total of 1200 kcal/day. All participants
      (n = 52) lost a significant amount of weight from baseline (-4.69 +/- 3.73 kg),
      which was further reflected in the reductions in their waist (-7.11 +/- 6.35 cm)
      and hip circumference (-5.59 +/- 3.58 cm) over the 12-week study (p < 0.0001).
      BMI scores (n = 51) were reduced by 1.6 +/- 1.4 kg/m(2). The use of PGX(r) meal
      replacements and PGX((r)) fibre along with a controlled dietary caloric intake is
      of benefit for short-term weight loss. 

PMID- 24568283
TI  - Generation of complexity in fungal terpene biosynthesis: discovery of a
      multifunctional cytochrome P450 in the fumagillin pathway.
AB  - Fumagillin (1), a meroterpenoid from Aspergillus fumigatus, is known for its
      antiangiogenic activity due to binding to human methionine aminopeptidase 2. 1
      has a highly oxygenated structure containing a penta-substituted cyclohexane that
      is generated by oxidative cleavage of the bicyclic sesquiterpene beta-trans
      bergamotene. The chemical nature, order, and biochemical mechanism of all the
      oxygenative tailoring reactions has remained enigmatic despite the identification
      of the biosynthetic gene cluster and the use of targeted-gene deletion
      experiments. Here, we report the identification and characterization of three
      oxygenases from the fumagillin biosynthetic pathway, including a multifunctional
      cytochrome P450 monooxygenase, a hydroxylating nonheme-iron-dependent
      dioxygenase, and an ABM family monooxygenase for oxidative cleavage of the
      polyketide moiety. Most significantly, the P450 monooxygenase is shown to
      catalyze successive hydroxylation, bicyclic ring-opening, and two epoxidations
      that generate the sesquiterpenoid core skeleton of 1. We also characterized a
      truncated polyketide synthase with a ketoreductase function that controls the
      configuration at C-5 of hydroxylated intermediates. 

PMID- 24568285
TI  - Prescription practices for chronic obstructive pulmonary disease: findings from
      the national ambulatory medical care survey 1999-2010.
AB  - Recent trends in prescriptions for medicines used to treat chronic obstructive
      pulmonary disease (COPD) in the United States have received little attention. Our
      objective was to examine trends in prescribing practices for medications used to
      treat COPD. We examined data from surveys of national samples of office visits to
      non-federal employed office-based physicians in the United States by patients
      aged >=40 years with COPD recorded by the National Ambulatory Medical Care Survey
      from 1999 to 2010. From three diagnostic codes, office visits by patients with
      COPD were identified. Prescribed medications were identified from up to 8
      recorded medications. The percentage of these visits during which a prescription
      for any medication used to treat COPD was issued increased from 27.0% in 1999 to
      49.1% in 2010 (p trend < 0.001). Strong increases were noted for short-acting
      beta-2 agonists (17.6% in 1999 to 24.7% in 2010; p trend < 0.001), long-acting
      beta-2 agonists as single agents or combination products (6.2% in 1999 to 28.3%
      in 2010; p trend < 0.001), inhaled corticosteroids as single agents or
      combination products (10.9% in 1999 to 30.9% in 2010; p trend < 0.001), and
      tiotropium (3.8% in 2004 to 17.2% in 2010; p trend < 0.001). Since 1999,
      prescription patterns for medicines used to treat COPD have changed profoundly in
      the United States.

PMID- 24568284
TI  - Clickable, hydrophilic ligand for fac-[M(I)(CO)3](+) (M = Re/(99m)Tc) applied in
      an S-functionalized alpha-MSH peptide.
AB  - The copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) click reaction was
      used to incorporate alkyne-functionalized dipicolylamine (DPA) ligands (1 and 3)
      for fac-[M(I)(CO)3](+) (M = Re/(99m)Tc) complexation into an alpha-melanocyte
      stimulating hormone (alpha-MSH) peptide analogue. A novel DPA ligand with
      carboxylate substitutions on the pyridyl rings (3) was designed to increase the
      hydrophilicity and to decrease in vivo hepatobiliary retention of fac
      [(99m)Tc(I)(CO)3](+) complexes used in single photon emission computed tomography
      (SPECT) imaging studies with targeting biomolecules. The fac-[Re(I)(CO)3(3)]
      complex (4) was used for chemical characterization and X-ray crystal analysis
      prior to radiolabeling studies between 3 and fac-[(99m)Tc(I)(OH2)3(CO)3](+). The
      corresponding (99m)Tc complex (4a) was obtained in high radiochemical yields, was
      stable in vitro for 24 h during amino acid challenge and serum stability assays,
      and showed increased hydrophilicity by log P analysis compared to an analogous
      complex with nonfunctionalized pyridine rings (2a). An alpha-MSH peptide
      functionalized with an azide was labeled with fac-[M(I)(CO)3](+) using both
      click, then chelate (CuAAC reaction with 1 or 3 followed by metal complexation)
      and chelate, then click (metal complexation of 1 and 3 followed by CuAAC with the
      peptide) strategies to assess the effects of CuAAC conditions on fac
      [M(I)(CO)3](+) complexation within a peptide framework. The peptides from the
      click, then chelate strategy had different HPLC tR's and in vitro stabilities
      compared to those from the chelate, then click strategy, suggesting nonspecific
      coordination of fac-[M(I)(CO)3](+) using this synthetic route. The fac
      [M(I)(CO)3](+)-complexed peptides from the chelate, then click strategy showed
      >90% stability during in vitro challenge conditions for 6 h, demonstrated high
      affinity and specificity for the melanocortin 1 receptor (MC1R) in IC50 analyses,
      and led to moderately high uptake in B16F10 melanoma cells. Log P analysis of the
      (99m)Tc-labeled peptides confirmed the enhanced hydrophilicity of the peptide
      bearing the novel, carboxylate-functionalized DPA chelate (10a') compared to the
      peptide with the unmodified DPA chelate (9a'). In vivo biodistribution analysis
      of 9a' and 10a' showed moderate tumor uptake in a B16F10 melanoma xenograft mouse
      model with enhanced renal uptake and surprising intestinal uptake for 10a'
      compared to predominantly hepatic accumulation for 9a'. These results, coupled
      with the versatility of CuAAC, suggests this novel, hydrophilic chelate can be
      incorporated into numerous biomolecules containing azides for generating targeted
      fac-[M(I)(CO)3](+) complexes in future studies. 

PMID- 24568286
TI  - Prevalence and influencing factors of chronic back pain among staff at special
      schools with multiple and severely handicapped children in Germany: results of a
      cross-sectional study.
AB  - BACKGROUND: In Germany, about 70,000 teachers and educational staff were teaching
      at more than 3,000 special schools during the school year 2010/2011. Nursing
      services like lifting pupils form a substantial part of the work content of the
      staff at special schools. Since nursing care often involves carrying and lifting
      pupils, there is a reason to assume an adverse effect on the musculoskeletal
      health of teachers and other professionals. With the present study we aimed to
      describe the prevalence and risk factors of chronic back pain among employees at
      this type of school. METHODS: The cross-sectional survey was carried out between
      August 2010 and August 2012 at 13 special schools focusing on motoric and/or
      holistic development of handicapped children in Rhineland-Palatinate (Germany).
      Teachers and educational staff were interviewed using a questionnaire. We applied
      multivariable logistic regression analyses to identify influencing factors of
      chronic back pain. RESULTS: Altogether 395 persons (response rate: 59.7%)
      participated in our study. Respondents were mostly female (86.8%) with a mean age
      of 45 years. The prevalence of chronic back pain was 38.7%. More than 40%
      reported frequently carrying and lifting heavy loads (>20 kg). Age [adjusted OR =
      1.03 (95%-CI 1.00-1.05) for 1-year increase in age], current smoking [adjusted OR
      = 2.31 (95%-CI 1.27-4.23)], depression/depressive mood [adjusted OR = 1.85 (95%
      CI 1.12-3.06)], frequently carrying and lifting heavy loads [adjusted OR = 2.69
      (95%-CI 1.53-4.75)], and frequent exposure to environmental impacts [adjusted OR
      = 2.18 (95%-CI 1.26-3.76)] were influencing factors of chronic back pain in the
      final multivariable regression model. CONCLUSIONS: A large proportion of teachers
      and educational staff suffered from chronic back pain in our study, indicating a
      high need for treatment in this professional group. Increasing age, current
      smoking, a diagnosed depression/depressive mood, carrying and lifting heavy
      loads, and exposure to environmental impacts were associated with chronic back
      pain. Due to the sparse literature on the topic, further studies using a
      longitudinal design are necessary for a better understanding of the risk factors
      of chronic back pain.

PMID- 24568287
TI  - Major components of metabolic syndrome and adiponectin levels: a cross-sectional
      study.
AB  - BACKGROUND: Adiponectin is a major regulator of glucose and lipid homeostasis by
      its insulin sensitizer properties. Since decreased insulin sensitivity is linked
      to metabolic syndrome (MS), decreased adiponectin levels may be related to its
      development. The purpose of the study was to investigate the relationship between
      adiponectin levels and MS. METHODS: Firstly, we cross-sectionally examined
      subjects with or without MS submitted to an oral glucose tolerance test at
      Hospital de Clinicas de Porto Alegre (n = 172). A replication analysis was
      performed in subjects (n = 422) undergoing cardiac angiography at Hospital Sao
      Paulo. Subchronic inflammation (US-CRP), coagulation marker (fibrinogen), insulin
      sensitivity and resistance (Matsuda ISI and HOMA-IR) were estimated. Plasma total
      and high molecular weight (HMW) adiponectin were measured. RESULTS: Total and HMW
      adiponectin levels were lower in MS subjects (P < 0.05). Total adiponectin levels
      were lower in the presence of high waist circumference, low HDL-cholesterol and
      elevated triglyceride criteria in both samples and by elevated blood pressure and
      glucose criteria in Porto Alegre. HMW adiponectin levels were lower in the
      presence of low HDL-cholesterol, elevated triglycerides, and glucose criteria.
      Total adiponectin levels were positively related with HDL-cholesterol and ISI
      Matsuda, negatively related with waist circumference, glucose, triglycerides,
      HOMA-IR, and US-CRP and not related with blood pressure. While adjusting for sex
      and age, increased adiponectin levels remained associated with a reduced
      prevalence ratio for MS in both cohorts (P = 0.001). CONCLUSIONS: Adiponectin
      levels decreased with increasing number of MS criteria, and it is in part
      determined by its relationship with HDL, triglycerides and abdominal adiposity.

PMID- 24568289
TI  - Evaluation of physical properties of different digital intraoral sensors.
AB  - OBJECTIVE: Digital technologies provide clinically acceptable results comparable
      to traditional films while having other advantages such as the ability to store
      and manipulate images, immediate evaluation of the image diagnostic quality,
      possible reduction in patient radiation exposure, and so on. The purpose of this
      paper is to present the results of the evaluation of the physical design of eight
      CMOS digital intraoral sensors. METHODS: Sensors tested included: XDR (Cyber
      Medical Imaging, Los Angeles, CA, USA), RVG 6100 (Carestream Dental LLC, Atlanta,
      GA, USA), Platinum (DEXIS LLC., Hatfield, PA, USA), CDR Elite (Schick
      Technologies, Long Island City, NY, USA), ProSensor (Planmeca, Helsinki,
      Finland), EVA (ImageWorks, Elmsford, NY, USA), XIOS Plus (Sirona, Bensheim,
      Germany), and GXS-700 (Gendex Dental Systems, Hatfield, PA, USA). The sensors
      were evaluated for cable configuration, connectivity interface, presence of back
      scattering radiation shield, plate thickness, active sensor area, and comparing
      the active imaging area to the outside casing and to conventional radiographic
      films. RESULTS: There were variations among the physical design of different
      sensors. For most parameters tested, a lack of standardization exists in the
      industry. The results of this study revealed that these details are not always
      available through the material provided by the manufacturers and are often not
      advertised. For all sensor sizes, active imaging area was smaller compared with
      conventional films. CONCLUSIONS: There was no sensor in the group that had the
      best physical design. Data presented in this paper establishes a benchmark for
      comparing the physical design of digital intraoral sensors.

PMID- 24568288
TI  - Two novel amphomycin analogues from Streptomyces canus strain FIM-0916.
AB  - Three lipopeptides, the known compound amphomycin, together with two novel
      compounds named aspartocin D (1) and aspartocin E (2) were obtained from the
      fermentation broth extraction of Streptomyces canus strain FIM0916 by using
      various column chromatography techniques. Their structures were elucidated by
      using spectroscopic methods, mainly by an extensive NMR analysis. It was
      demonstrated that compounds 1 and 2 are novel analogues of amphomycin, whose
      structures are similar to aspartocins. Compounds 1 and 2 share the same cyclic
      decapeptide core of cyclo (Dab2-Pip3-MeAsp4-Asp5-Gly6-Asp7-Gly8-Dab9-Val10-Pro11
      ), differing only in the side-chain moiety corresponding to Asp1-?3
      isohendecenoic acid and Asp1-?3-isododecenoic acid, for aspartocin D and
      aspartocin E. In bioassays, compounds 1 and 2 exhibited antimicrobial activities
      against Gram-positive bacteria in the presence of Ca(2+) (1.25 mM); particularly,
      the activities were enhanced with higher concentrations of calcium.

PMID- 24568290
TI  - Maxillofacial prosthetics: history to modern applications. Part 1 - obturators.
AB  - The role of the maxillofacial prosthodontist in the treatment of head and neck
      cancer patients is not well understood in the medical community. Frequently,
      dental professionals are called upon by physicians to provide advice regarding
      the complex needs of head and neck cancer patients. Most general dentists have
      had limited training in this area. The general dentist has the opportunity to
      provide the bridge between the physician and the maxillofacial prosthodontist,
      who can provide treatment information to both the general dentist and the
      physician. A better understanding of maxillofacial prosthodontics can clarify
      which patients should be referred to a maxillofacial prosthodontist for
      treatment. 

PMID- 24568292
TI  - Epidemiology of type 1 diabetes in Latin America.
AB  - Latin America is among the regions with the highest diabetes-related burden.
      Research and treatment programs have increased in number and complexity in recent
      years, but they are focused in type 2 diabetes, because this condition explains a
      large proportion of the cases. In contrast, the information regarding the
      epidemiology of type 1 diabetes is scant in this area. Here, we analyze the
      available information on this topic and identify potential areas of opportunity
      to generate new knowledge through the study of type 1 diabetes in Latin
      Americans. Both, the prevalence and the incidence of type 1 diabetes, are lower
      in Latin American countries compared to that reported in Europe, North America,
      southern Asia and northern Africa. Biologic and methodological factors may
      explain the smaller contribution of type 1. The presence of some putative
      'protective' environmental exposures or the absence of those prevalent in a
      region may explain the lower type 1 diabetes prevalence observed in most Latin
      American countries. However, the number and quality of the diabetes registries
      are not enough in this region. During the past decade, the incidence of type 1
      diabetes has grown worldwide. The same trend has been reported in Latin America.
      This epidemiologic transition is a unique opportunity to identify interactions
      between rapidly changing environmental factors in subjects with different genetic
      backgrounds (such as the admixed Latin American populations). Finally, on-going
      therapeutic initiatives in this region are highlighted. 

PMID- 24568291
TI  - Correction of methylmalonic aciduria in vivo using a codon-optimized lentiviral
      vector.
AB  - Methylmalonic aciduria is a rare disorder of organic acid metabolism with limited
      therapeutic options, resulting in high morbidity and mortality. Positive results
      from combined liver/kidney transplantation suggest, however, that metabolic sink
      therapy may be efficacious. Gene therapy offers a more accessible approach for
      the treatment of methylmalonic aciduria than organ transplantation. Accordingly,
      we have evaluated a lentiviral vector-mediated gene transfer approach in an in
      vivo mouse model of methylmalonic aciduria. A mouse model of methylmalonic
      aciduria (Mut(-/-)MUT(h2)) was injected intravenously at 8 weeks of age with a
      lentiviral vector that expressed a codon-optimized human methylmalonyl coenzyme A
      mutase transgene, HIV-1SDmEF1alphamurSigHutMCM. Untreated Mut(-/-)MUT(h2) and
      normal mice were used as controls. HIV-1SDmEF1alphamurSigHutMCM-treated mice
      achieved near-normal weight for age, and Western blot analysis demonstrated
      significant methylmalonyl coenzyme A enzyme expression in their livers.
      Normalization of liver methylmalonyl coenzyme A enzyme activity in the treated
      group was associated with a reduction in plasma and urine methylmalonic acid
      levels, and a reduction in the hepatic methylmalonic acid concentration.
      Administration of the HIV-1SDmEF1alphamurSigHutMCM vector provided significant,
      although incomplete, biochemical correction of methylmalonic aciduria in a mouse
      model, suggesting that gene therapy is a potential treatment for this disorder.

PMID- 24568295
TI  - Controlling the excited state and photosensitizing property of a 2-(2
      pyridyl)benzo[b]thiophene-based cationic iridium complex through simple chemical
      modification.
AB  - Bis-cyclometalated cationic iridium (Ir) complexes 1-4 comprising two 2-(2
      pyridyl)benzo[b]thiophene (btp) ligands and one 2,2'-bipyridyl (bpy) ancillary
      ligand with different substituents were prepared as new visible light-absorbing
      sensitizers and examined for their photophysical and electrochemical properties.
      Complex 1 was prepared as a parent complex without any substituents. Complexes 2
      4 contained methyl-, methoxy-, and trifluoromethyl groups at 4,4'-positions on
      the bpy ancillary ligand. Systematic investigation of these complexes revealed
      that such a simple chemical modification selectively controls the excited-state
      lifetime, while the absorption and emission spectral features remain unchanged.
      Specifically, the phosphorescence lifetimes of complexes 2 and 3 with electron
      donating groups (tau = 3.50 MUs, 3.90 MUs) were found to be much longer than that
      of complex 1 (tau = 0.273 MUs), and complex 4, possessing strong electron
      withdrawing trifluoromethyl groups, did not exhibit detectable phosphorescence at
      room temperature. The large differences in excited-state lifetimes of complexes 1
      3, as well as the nonemissive character of complex 4, are attributed to a strong
      influence of the substituents on the ligand field strength. The increased sigma
      donating ability of the ancillary ligand in complexes 2 and 3 destabilizes a
      short-lived, nonemissive triplet metal-centered ((3)MC) state and increases the
      energy separation between the (3)MC state and emissive triplet ligand-centered
      ((3)LC) state based on the btp ligand. For complex 4, however, the (3)MC state is
      close in energy to the (3)LC state because of the decreased sigma-donating
      ability of the ancillary ligand. Additional evidence of the (3)MC state
      associated with the changeable excited state was also provided via low
      temperature phosphorescence measurements and density functional theory
      calculations. Ir complexes 1-4 were tested as sensitizers in photoinduced
      electron-transfer reaction of triethanolamine and methylviologen chloride
      (MVCl2). As a result, complexes 2 and 3 exhibited much better photosensitizing
      property compared to complex 1 since their long-lived excited states promoted an
      oxidative quenching pathway. This Study has first demonstrated that simple
      substitution on the diimine ancillary ligand can control the (3)MC state of the
      bis-cyclometalated cationic Ir complex to finely tune the excited-state lifetime
      and photosensitizing property. 

PMID- 24568296
TI  - Synthesis of taurine-containing peptides, sulfonopeptides, and N- and O
      conjugates.
AB  - Taurine-containing water-soluble peptidomimetics were designed and synthesized. N
      terminal taurine acylations allowed synthesis of a number of taurine-containing
      peptides. N-protection of taurine with Cbz and SO2-activation with benzotriazole
      followed by coupling with various amino esters, dipeptides and nucleophiles
      provided taurine N- and O-conjugates and sulfonopeptides. 

PMID- 24568297
TI  - The DNA-binding and bioactivity of rare earth metal complexes.
AB  - Recently more and more attention is paid to the rare earth metal complexes,
      because the properties of the rare earth metals are similar to those of the
      transition metals such as the similar atomic and the ionic radius. A large number
      of rare metal complexes were synthesized, and their bioactivities were also
      studied. This review highlights recent researches on the interaction of some rare
      earth metal complexes with DNA, analyzes how the configuration of the complexes
      influences the binding affinity, and focuses on the pharmacological activities of
      the complexes, such as anticancer, antibacterial, antioxidant, anti-inflammatory
      and anti-virus. 

PMID- 24568298
TI  - Binding modes of chain arylpiperazines to 5-HT1a, 5-HT2a and 5-HT7 receptors.
AB  - An overview of docking models of chain arylpiperazines to different subtypes of
      serotonin receptors belonging to the GPCR family is presented. The theory of a
      ligand-receptor interaction has been briefly summarized. The review covers more
      than twenty models, beginning with the early models of a ligand interaction with
      the 5-HT1A and 5-HT2A receptor, and ending with a ligand-5-HT7 receptor docking
      studies. 

PMID- 24568301
TI  - The management of agitation among inpatients in a brain injury rehabilitation
      unit.
AB  - OBJECTIVE: Agitation post-acquired brain injury (ABI) is common and should be
      appropriately managed to optimize the patients' rehabilitation progress. The
      objective of this study was to assess how agitation is managed in current
      practice on an ABI rehabilitation unit. METHODS: A retrospective chart audit was
      conducted of patients admitted to an ABI rehabilitation unit to assess current
      practices. All information pertaining to agitation was abstracted from the
      patients' medical chart (e.g. behavioural incidences, medication information and
      behavioural outcome measures). The Agitated Behavior Scale (ABS) was the only
      assessment tool regularly utilized and, therefore, its use was evaluated.
      RESULTS: A total of 102 patient charts were reviewed. Fifty-one patients received
      medication for agitated behaviour. The ABS was administered to 28 patients; a
      total of 124 ABS tests were completed for these patients. Twenty-one of the 28
      individuals never scored outside the 'normal' range; however, medications were
      given to 50%. CONCLUSIONS: The ABS and similar behavioural tools allow for a
      patient's behavioural patterns to be monitored and care plans to be created and
      executed according to evidence-based practices. There is a need to educate on the
      proper use and interpretation of assessment tools in order to improve care.

PMID- 24568300
TI  - PTSD and TBI co-morbidity: scope, clinical presentation and treatment options.
AB  - PRIMARY OBJECTIVE: To summarize the literature on post-traumatic stress disorder
      (PTSD) and traumatic brain injury (TBI) and their co-morbidity, focusing on
      diagnosis, clinical symptoms and treatment issues relevant to the clinician.
      RESEARCH DESIGN: Review of the literature. METHODS AND PROCEDURES: Pubmed
      searches were performed using the terms post-traumatic stress disorder, traumatic
      brain injury, sleep, cognitive, depression, anxiety, treatment and combinations
      of these terms. Those articles relevant to the objective were included. MAIN
      OUTCOMES AND RESULTS: This study presents pathophysiological, neuroimaging and
      clinical data on co-morbid PTSD and TBI. It reviews associated conditions,
      emphasizing the impact of cognitive and sleep problems. It summarizes the
      emerging literature on treatment effectiveness for co-morbid PTSD and TBI,
      including psychotherapy, pharmacotherapy and cognitive rehabilitation.
      CONCLUSIONS: Both PTSD and TBI commonly occur in the general population, both
      share some pathophysiological characteristics and both are associated with
      cognitive impairment and sleep disruption. PTSD and TBI present with a number of
      overlapping symptoms, which can lead to over-diagnosis or misdiagnosis. Both
      conditions are associated with co-morbidities important in diagnosis and
      treatment planning. More research is needed to elucidate what treatments are
      effective in PTSD and TBI co-morbidity and on factors predictive of treatment
      success.

PMID- 24568304
TI  - Vertically aligned N-doped coral-like carbon fiber arrays as efficient air
      electrodes for high-performance nonaqueous Li-O2 batteries.
AB  - High energy efficiency and long cycleability are two important performance
      measures for Li-air batteries. Using a rationally designed oxygen electrode based
      on a vertically aligned nitrogen-doped coral-like carbon nanofiber (VA-NCCF)
      array supported by stainless steel cloth, we have developed a nonaqueous Li-O2
      battery with an energy efficiency as high as 90% and a narrow voltage gap of 0.3
      V between discharge/charge plateaus. Excellent reversibility and cycleability
      were also demonstrated for the newly developed oxygen electrode. The observed
      outstanding performance can be attributed to its unique vertically aligned, coral
      like N-doped carbon microstructure with a high catalytic activity and an
      optimized oxygen/electron transportation capability, coupled with the microporous
      stainless steel substrate. These results demonstrate that highly efficient and
      reversible Li-O2 batteries are feasible by using a rationally designed carbon
      based oxygen electrode. 

PMID- 24568299
TI  - Yoga vs. physical therapy vs. education for chronic low back pain in
      predominantly minority populations: study protocol for a randomized controlled
      trial.
AB  - BACKGROUND: Chronic low back pain causes substantial morbidity and cost to
      society while disproportionately impacting low-income and minority adults.
      Several randomized controlled trials show yoga is an effective treatment.
      However, the comparative effectiveness of yoga and physical therapy, a common
      mainstream treatment for chronic low back pain, is unknown. METHODS/DESIGN: This
      is a randomized controlled trial for 320 predominantly low-income minority adults
      with chronic low back pain, comparing yoga, physical therapy, and education.
      Inclusion criteria are adults 18-64 years old with non-specific low back pain
      lasting >= 12 weeks and a self-reported average pain intensity of >= 4 on a 0-10
      scale. Recruitment takes place at Boston Medical Center, an urban academic safety
      net hospital and seven federally qualified community health centers located in
      diverse neighborhoods. The 52-week study has an initial 12-week Treatment Phase
      where participants are randomized in a 2:2:1 ratio into i) a standardized weekly
      hatha yoga class supplemented by home practice; ii) a standardized evidence-based
      exercise therapy protocol adapted from the Treatment Based Classification method,
      individually delivered by a physical therapist and supplemented by home practice;
      and iii) education delivered through a self-care book. Co-primary outcome
      measures are 12-week pain intensity measured on an 11-point numerical rating
      scale and back-specific function measured using the modified Roland Morris
      Disability Questionnaire. In the subsequent 40-week Maintenance Phase, yoga
      participants are re-randomized in a 1:1 ratio to either structured maintenance
      yoga classes or home practice only. Physical therapy participants are similarly
      re-randomized to either five booster sessions or home practice only. Education
      participants continue to follow recommendations of educational materials. We will
      also assess cost effectiveness from the perspectives of the individual, insurers,
      and society using claims databases, electronic medical records, self-report cost
      data, and study records. Qualitative data from interviews will add subjective
      detail to complement quantitative data. TRIAL REGISTRATION: This trial is
      registered in ClinicalTrials.gov, with the ID number: NCT01343927.

PMID- 24568302
TI  - Front-office/back-office configurations and operational performance in complex
      health services.
AB  - BACKGROUND: Acquired brain injury (ABI) occurs from various causes at different
      ages and leads to many different types of healthcare needs. Several Dutch ABI
      networks installed a local co-ordination and contact point (CCP) which functions
      as a central and easily accessible service for people to consult when they have
      questions related to ABI. GOALS: To explore the relationship between front/back
      office design and operational performance by investigating the particular enquiry
      service provided by different CCPs for people affected by an ABI. METHODS: In
      depth interviews with 14 FO/BO employees from three case organizations,
      complemented with information from desk research and three one-day field visits.
      RESULTS: The CCPs applied different FO/BO configurations in terms of customer
      contact and in terms of grouping of front and/or back office activities into
      tasks for one employee. DISCUSSION: It is the complexity of the enquiry that
      determines which approach is more appropriate. For complex enquiries, the level
      of decoupling is high in all CCPs. This allows multiple experts to be involved in
      the process. For regular enquiries, CCPs have a choice: either working in the
      same way as in the complex enquiries or coupling FO/BO activities to be able to
      serve clients faster and without handovers.

PMID- 24568305
TI  - The value of diastolic function parameters in the prediction of left atrial
      appendage thrombus in patients with nonvalvular atrial fibrillation.
AB  - BACKGROUND: Left ventricular diastolic impairment and consequently elevated
      filling pressure may contribute to stasis leading to left atrial appendage
      thrombus (LAAT) in nonvalvular atrial fibrillation (AF). We investigated whether
      transthoracic echocardiographic parameters can predict LAAT independent of
      traditional clinical predictors. METHODS: We conducted a retrospective cohort
      study of 297 consecutive nonvalvular AF patients who underwent transthoracic
      echocardiogram followed by a transesophageal echocardiogram within one year.
      Multivariate logistic regression analysis models were used to determine factors
      independently associated with LAAT. RESULTS: Nineteen subjects (6.4%) were
      demonstrated to have LAAT by transesophageal echocardiography. These patients had
      higher mean CHADS2 scores [2.6 +/- 1.2 vs. 1.9 +/- 1.3, P = 0.009], higher E:e'
      ratios [16.6 +/- 6.1 vs. 12.0 +/- 5.4, P = 0.001], and lower mean e' velocities
      [6.5 +/- 2.1 cm/sec vs. 9.1 +/- 3.2 cm/sec, P = 0.001]. Both E:e' and e' velocity
      were associated with LAAT formation independent of the CHADS2 score, warfarin
      therapy, left ventricular ejection fraction (LVEF), and left atrial volume index
      (LAVI) [E:e' odds-ratio = 1.14 (95% confidence interval = 1.03 - 1.3), P = 0.009;
      e' velocity odds-ratio = 0.68 (95% confidence interval = 0.5 - 0.9), P = 0.007].
      Similarly, diastolic function parameters were independently associated with
      spontaneous echo contrast. CONCLUSION: The diastolic function indices E:e' and e'
      velocity are independently associated with LAAT in nonvalvular AF patients and
      may help identify patients at risk for LAAT.

PMID- 24568307
TI  - Policy implications of environmental research remain untouched by proposed trade
      agreements.

PMID- 24568306
TI  - A summary of research and progress on carbon monoxide exposure control solutions
      on houseboats.
AB  - Investigations of carbon monoxide (CO-related poisonings and deaths on houseboats
      were conducted by the Centers for Disease Control and Prevention, National
      Institute for Occupational Safety and Health. These investigations measured
      hazardous CO concentrations on and around houseboats that utilize gasoline
      powered generators. Engineering control devices were developed and tested to
      mitigate this deadly hazard. CO emissions were measured using various sampling
      techniques which included exhaust emission analyzers, detector tubes, evacuated
      containers (grab air samples analyzed by a gas chromatograph), and direct-reading
      CO monitors. CO results on houseboats equipped with gasoline-powered generators
      without emission controls indicated hazardous CO concentrations exceeding
      immediately dangerous to life and health (IDLH) levels in potentially occupied
      areas of the houseboat. Air sample results on houseboats that were equipped with
      engineering controls to remove the hazard were highly effective and reduced CO
      levels by over 98% in potentially occupied areas. The engineering control devices
      used to reduce the hazardous CO emissions from gasoline-powered generators on
      houseboats were extremely effective at reducing CO concentrations to safe levels
      in potentially occupied areas on the houseboats and are now beginning to be
      widely used. 

PMID- 24568308
TI  - Anatomic maxillary sinus balloon for orbital floor repair: a preliminary
      volumetric study.

PMID- 24568310
TI  - Histochemical investigation of Cochlospermum regium (Schrank) Pilg. leaves and
      chemical composition of its essential oil.
AB  - Essential oil from Cochlospermum regium (Schrank) Pilg. leaves (CR-EO) has been
      extracted by hydrodistillation; we analysed the CR-EO by gas chromatography
      coupled with mass spectrometry. We also conducted histochemical analysis on cross
      sections of the central vein of young and adult leaves. A total of 32 compounds
      were qualitatively and quantitatively analysed, which represented 94.87% of the
      total CR-EO oil content. The CR-EO basically consisted of sesquiterpenes
      (96.87%); its main component was beta-copaen-4-alpha-ol (18.73%), followed by
      viridiflorol (12.67%). The histochemical analyses identified the main classes of
      compounds present in both young and adult leaves. 

PMID- 24568311
TI  - Performance of ParacheckTM-Pf, SD Bioline malaria Ag-Pf and SD Bioline malaria Ag
      Pf/pan for diagnosis of falciparum malaria in the Central African Republic.
AB  - BACKGROUND: Rapid diagnostic tests (RDTs) are the current complement to
      microscopy for ensuring prompt malaria treatment. We determined the performance
      of three candidate RDTs (ParacheckTM-Pf, SD Bioline malaria Ag-Pf and SD Bioline
      malaria Ag-Pf/pan) for rapid diagnosis of malaria in the Central African
      Republic. METHODS: Blood samples from consecutive febrile patients who attended
      for laboratory analysis of malaria at the three main health centres of Bangui
      were screened by microscopy and the RDTs. Two reference standards were used to
      assess the performance of the RDTs: microscopy and, a combination of microscopy
      plus nested PCR for slides reported as negative, on the assumption that negative
      results by microscopy were due to sub-patent parasitaemia. RESULTS: We analysed
      436 samples. Using the combined reference standard of microscopy + PCR, the
      sensitivity of ParacheckTM-Pf was 85.7% (95% CI, 80.8-89.8%), that of SD Bioline
      Ag-Pf was 85.4% (95% CI, 80.5-90.7%), and that of SD Bioline Ag-Pf/pan was 88.2%
      (95% CI, 83.2-92.0%). The tests performed less well in cases of low parasitaemia;
      however, the sensitivity was > 95% at > 500 parasites/MUl. CONCLUSIONS: Overall,
      SD Bioline malaria Ag-Pf and SD Bioline malaria Ag-Pf/pan performed slightly
      better than ParacheckTM-Pf. Use of RDTs with reinforced microscopy practice and
      laboratory quality assurance should improve malaria treatment in the Central
      African Republic.

PMID- 24568313
TI  - Novel spiroketal pyrrolidine GSK2336805 potently inhibits key hepatitis C virus
      genotype 1b mutants: from lead to clinical compound.
AB  - Rapid clinical progress of hepatitis C virus (HCV) replication inhibitors,
      including these selecting for resistance in the NS5A region (NS5A inhibitors),
      promises to revolutionize HCV treatment. Herein, we describe our explorations of
      diverse spiropyrrolidine motifs in novel NS5A inhibitors and a proposed
      interaction model. We discovered that the 1,4-dioxa-7-azaspiro[4.4]nonane motif
      in inhibitor 41H (GSK2236805) supported high potency against genotypes 1a and 1b
      as well as in genotype 1b L31V and Y93H mutants. Consistent with this, 41H
      potently suppressed HCV RNA in the 20-day RNA reduction assay. Pharmacokinetic
      and safety data supported further progression of 41H to the clinic. 

PMID- 24568314
TI  - Identification and quantification of grapefruit juice furanocoumarin metabolites
      in urine: an approach based on ultraperformance liquid chromatography coupled to
      linear ion trap-Orbitrap mass spectrometry and solid-phase extraction coupled to
      ultraperformance liquid chromatography coupled to triple quadrupole-tandem mass
      spectrometry.
AB  - Grapefruit is a rich source of flavonoids but also contains furanocoumarins,
      which are known to strongly interact with a variety of medications. Thus,
      characterization of grapefruit furanocoumarin metabolites may help in a better
      understanding of grapefruit-drug interactions. In the present work,
      identification of the main metabolites of grapefruit juice furanocoumarins in
      urine was performed by ultraperformance liquid chromatography (UPLC) coupled to
      linear ion trap-Orbitrap mass spectrometry (LTQ-Orbitrap). Glucuronides of 6',7'
      dihydroxybergamottin and a hydroxybergamottin-like metabolite were identified for
      the first time as grapefruit juice metabolites. Afterward, a fast and sensitive
      method based on solid-phase extraction (SPE) and UPLC coupled to triple
      quadrupole-tandem mass spectrometry (QqQ-MS/MS) was developed for determination
      of the identified metabolites in urine. The proposed method was applied to urine
      samples of five volunteers after intakes of moderate doses of grapefruit, lemon,
      and orange juices. Furanocoumarin metabolites were only detected in urines after
      consumption of grapefruit juice. 

PMID- 24568312
TI  - Epithelial-mesenchymal transition enhances response to oncolytic herpesviral
      therapy through nectin-1.
AB  - Cancers exhibiting epithelial-mesenchymal transition (EMT) are associated with
      aggressive behavior and increased metastatic potential. Therapies that are able
      to target EMT would have significant clinical value. Nectin-1 is a cell surface
      herpes simplex virus type 1 (HSV-1) receptor that also forms a component of
      intercellular adherens junctions, which are typically disrupted in EMT. To
      explore relationships between HSV-1 sensitivity and EMT, we generated cell lines
      with a stable EMT phenotype from human follicular thyroid cancer (WRO82-1)
      through E-cadherin silencing with short hairpin RNA (shEcadWRO). HSV-1 viral
      attachment and gene expression were both enhanced in shEcadWRO as compared with
      shControl. Immunoblotting and immunostaining revealed enhanced nectin-1
      expression by shEcadWRO. Receptor-blocking assays demonstrated that increased
      herpesviral entry into shEcadWRO as compared with shControl was mediated
      predominantly through nectin-1. Colocalization of green fluorescent protein
      tagged HSV-1 and tdTomato-tagged nectin-1 confirmed an increase in viral
      attachment to nectin-1 in shEcadWRO. Cell viability assays demonstrated increased
      susceptibility of shEcadWRO to HSV-1 oncolysis, and a murine flank tumor model
      showed significantly enhanced regression of shEcadWRO tumors in response to
      oncolytic HSV-1 as compared with control tumors. A separate model of EMT
      induction through transforming growth factor-beta stimulation confirmed enhanced
      HSV-1 susceptibility in Panc1 cells. These results demonstrate that the process
      of EMT leads to increased herpesviral susceptibility through enhanced cell
      surface nectin-1 expression, suggesting that cancers exhibiting EMT may be
      naturally sensitive targets for herpesviral therapy.

PMID- 24568315
TI  - Socioeconomic status and prognosis of COPD in Denmark.
AB  - We investigated the association between length of school education and 5-year
      prognosis of chronic obstructive lung disease (COPD), including exacerbations,
      hospital admissions and survival. We used sample of general population from two
      independent population studies: The Copenhagen City Heart Study and Copenhagen
      General Population Study. A total of 6,590 individuals from general population of
      Copenhagen with COPD defined by the Global initiative for obstructive lung
      disease criteria were subdivided into 4 groups based on the length of school
      education: 1,590 with education < 8 years; 3,131 with education 8-10 years, 1,244
      with more than 10 years, but no college/university education and 625 with
      college/university education. Compared with long education, short education was
      associated with current smoking (p < 0.001), higher prevalence of respiratory
      symptoms (p < 0.001) and lower forced expiratory volume in the first second in
      percent of predicted value (FEV1%pred) (p < 0.001). Adjusting for sex, age,
      FEV1%pred, dyspnea, frequency of previous exacerbations and smoking we observed
      that shortest school education (in comparison with university education), was
      associated with a higher risk of COPD exacerbations (hazards ratio 1.65, 95% CI
      1.15-2.37) and higher risk of all-cause mortality (hazards ratio 1.96, 95% CI
      1.28-2.99). We conclude that even in an economically well-developed country with
      a health care system (which is largely free of charge), low socioeconomic status,
      assessed as the length of school education, is associated with a poorer clinical
      prognosis of COPD.

PMID- 24568317
TI  - Metallic foreign body deep in the prevertebral space after an endomyocardial
      biopsy: a case report.
AB  - INTRODUCTION: Although inspirated or ingested foreign bodies constitute a common
      otolaryngologic emergency, the removal of a solitary retained foreign body from
      the neck has seldom been described in the literature. The ingestion of foreign
      bodies commonly results in perforated viscose or extraluminal migration to
      adjacent structures quite a long period of time after the fact. To the best of
      our knowledge, this is the first English language description of an
      endomyocardial biopsy complicated by a retained foreign body deep in the
      prevertebral space of the patient's neck. We report such a case and share our
      experience in treating it. CASE PRESENTATION: A 68-year-old Asian man suffering
      right-sided heart failure underwent an endomyocardial biopsy via his right
      internal jugular vein. After undergoing the procedure, he was found to have
      retained a metallic cup tip which had become lodged in his neck. A surgeon then
      performed neck exploration and the foreign body was removed without adverse
      effect. CONCLUSIONS: Decision making as to whether to remove the foreign body or
      not remains controversial. However, the later incidence of adhesive fibrosis or,
      even worse, of a catastrophic abscess or adjacent vascular injury might occur if
      the foreign body was not removed. Early exploration is suggested, if the
      patient's condition makes this feasible.

PMID- 24568318
TI  - Laparoscopic colorectal surgery in patients with impaired renal function: impact
      on postoperative renal function compared with open surgery.
AB  - BACKGROUND: Laparoscopic surgery has been associated with a perioperative
      decrease in renal function. As a result, an open approach may be preferred in
      patients with impaired renal function when prolonged laparoscopic procedures are
      anticipated. The aim of this study was to examine changes in renal function
      following colorectal operations and compare between the open and the laparoscopic
      approaches, in patients with preoperative impaired renal function. PATIENTS AND
      METHODS: This is a single-center retrospective study. Records of all patients
      with impaired renal function (estimated glomerular filtration rate [eGFR] <60
      mL/minute) who underwent elective colorectal resection between 2007 and 2011 were
      reviewed. The changes in eGFR were examined and compared between open and
      laparoscopic procedures. RESULTS: Ninety consecutive patients with impaired renal
      function who underwent elective colorectal surgery from 2007 to 2011 were
      identified. Forty-seven patients underwent laparoscopic surgery, and 43 had an
      open surgery; 23.2% of the patients who had open surgery and 21.7% of the
      patients who underwent a laparoscopic procedure demonstrated a decrease in eGFR
      at the time of discharge (P=not significant). The mean decrease in eGFR did not
      differ between the two groups (6.3 +/- 6.8 mL/minute versus 4.04 +/- 4.01
      mL/minute; P=.34). None of the patients required dialysis. Postoperative
      complications were found to be a risk factor for a significant decrease in renal
      function. CONCLUSIONS: Renal function may deteriorate in patients with chronic
      kidney disease who undergo elective colorectal surgery. No difference was noted
      in the incidence or severity of such deterioration between open and laparoscopic
      approaches. Postoperative complications are associated with deterioration in
      renal function regardless of the operative approach.

PMID- 24568316
TI  - Cytocompatibility of novel extracellular matrix protein analogs of biodegradable
      polyester polymers derived from alpha-hydroxy amino acids.
AB  - One of the challenges in regenerative medicine is the development of novel
      biodegradable materials to build scaffolds that will support multiple cell types
      for tissue engineering. Here we describe the preparation, characterization, and
      cytocompatibility of homo- and hetero-polyesters of alpha-hydroxy amino acid
      derivatives with or without lactic acid conjugation. The polymers were prepared
      by a direct condensation method and characterized using gel permeation
      chromatography, (1)H-nuclear magnetic resonance spectroscopy, Fourier transform
      infrared spectroscopy, differential scanning calorimetry, optical activity, and
      solubility. The surface charge of the polymers was evaluated using zeta potential
      measurements. The polymers were coated onto glass cover slips followed by
      characterization using nano-surface profiler, thin film reflectometry, and atomic
      force microscopy (AFM). Their interaction with endothelial and neuronal cells was
      assessed using adhesion, proliferation, and differentiation assays. Of the
      characterized polymers, Poly-HOVal-LA, but not Poly-(D)HOPhe, significantly
      augmented nerve growth factor (NGF)-induced neuronal differentiation of the PC12
      pheochromcytoma cells. In contrast, Poly-HOLeu increased by 20% the adhesion of
      endothelial cells, but did not affect PC12 cell differentiation. NGF-induced
      Erk1/2 phosphorylation in PC12 cells grown on the different polymers was similar
      to the effect observed for cells cultured on collagen type I. While no
      significant association could be established between charge and the
      differentiative/proliferative properties of the polymers, AFM analysis indicated
      augmentation of NGF-induced neuronal differentiation on smooth polymer surfaces.
      We conclude that overall selective cytocompatibility and bioactivity might render
      alpha-hydroxy amino acid polymers useful as extracellular matrix-mimicking
      materials for tissue engineering. 

PMID- 24568319
TI  - Exposures and cross-shift lung function declines in wildland firefighters.
AB  - Respiratory problems are common among wildland firefighters. However, there are
      few studies directly linking occupational exposures to respiratory effects in
      this population. Our objective was to characterize wildland fire fighting
      occupational exposures and assess their associations with cross-shift changes in
      lung function. We studied 17 members of the Alpine Interagency Hotshot Crew with
      environmental sampling and pulmonary function testing during a large wildfire. We
      characterized particles by examining size distribution and mass concentration,
      and conducting elemental and morphological analyses. We examined associations
      between cross-shift lung function change and various analytes, including
      levoglucosan, an indicator of wood smoke from burning biomass. The levoglucosan
      component of the wildfire aerosol showed a predominantly bimodal size
      distribution: a coarse particle mode with a mass median aerodynamic diameter
      about 12 MUm and a fine particle mode with a mass median aerodynamic diameter <
      0.5 MUm. Levoglucosan was found mainly in the respirable fraction and its
      concentration was higher for fire line construction operations than for mop-up
      operations. Larger cross-shift declines in forced expiratory volume in one second
      were associated with exposure to higher concentrations of respirable levoglucosan
      (p < 0.05). Paired analyses of real-time personal air sampling measurements
      indicated that higher carbon monoxide (CO) concentrations were correlated with
      higher particulate concentrations when examined by mean values, but not by
      individual data points. However, low CO concentrations did not provide reliable
      assurance of concomitantly low particulate concentrations. We conclude that
      inhalation of fine smoke particles is associated with acute lung function decline
      in some wildland firefighters. Based on short-term findings, it appears important
      to address possible long-term respiratory health issues for wildland
      firefighters. [Supplementary materials are available for this article. Go to the
      publisher's online edition of Journal of Occupational and Environmental Hygiene
      for the following free supplemental resources: a file containing additional
      information on historical studies of wildland fire exposures, a file containing
      the daily-exposure-severity questionnaire completed by wildland firefighter
      participants at the end of each day, and a file containing additional details of
      the investigation of correlations between carbon monoxide concentrations and
      other measured exposure factors in the current study.]. 

PMID- 24568321
TI  - Top-down regulation of left temporal cortex by hypnotic amusia for rhythm: a
      pilot study on mismatch negativity.
AB  - To evaluate the effect of hypnotically induced amusia for rhythm (a condition in
      which individuals are unable to recognize melodies or rhythms) on mismatch
      negativity (MMN), 5 highly (HH) and 5 poorly (LH) hypnotizable nonmusician
      volunteers underwent MMN recording before and during a hypnotic suggestion for
      amusia. MMN amplitude was recorded using a 19-channel montage and then processed
      using the low-resolution electromagnetic tomography (LORETA) to localize its
      sources. MMN amplitude was significantly decreased during hypnotic amusia (p <
      .04) only in HH, where the LORETA maps of MMN showed a decreased source amplitude
      in the left temporal lobe, suggesting a hypnotic top-down regulation of activity
      of these areas and that these changes can be assessed by neurophysiological
      investigations.

PMID- 24568322
TI  - Dynamic hypnosis, IBS, and the value of individualizing treatment: a clinical
      perspective.
AB  - Hypnosis has already been proven efficient in treatment of irritable bowel
      syndrome (IBS). The author was responsible for the hypnotherapy in a Swedish
      study and adds her clinical experience with IBS patients within and beyond that
      study. The hypnosis was labeled dynamic, and the treatment utilized the
      therapists' clinical competence and individually tailored techniques, including
      gut-oriented symptom relief and hypnoanalysis, separately or in combination. The
      author presents 2 cases, 1 with a focus on symptom relief and 1 on exploring
      traumatic causes. She illustrates her clinical rationale for technical
      flexibility from trauma resolving hypnoanalysis to symptom-alleviating suggestive
      hypnosis, including dynamics beyond the symptom when such are part of the case
      history.

PMID- 24568323
TI  - The effect of hypnosis on dysmenorrhea.
AB  - This randomized control trial studied the effect of hypnosis on dysmenorrhea.
      Fifty eligible nursing students were randomly divided into 2 groups according to
      baseline pain scores. One group was given hypnosis and the other given
      medications for pain relief for 3 menstrual cycles, followed by 3 cycles without
      any treatment. They were evaluated for functional restriction of activity on a 3
      point scale. There was significant improvement in quality of life after the third
      cycle in both groups compared to baseline. The effect of hypnosis and medications
      on quality of life was similar in both groups at the third and sixth cycles.

PMID- 24568324
TI  - Application of hypno-dissociative strategies during dental treatment of patients
      with severe dental phobia.
AB  - Dental phobia is a well-known condition that may prevent patients from receiving
      adequate dental care. Dentists offer varied methods to help their patients
      overcome their phobic reactions and to enable them to proceed with needed dental
      treatment. These methods include diverse medical and behavioral interventions
      that are generally intended to regulate physiological, behavioral, cognitive, and
      emotional expressions of stress. Some patients with severe dental phobia together
      with actual or assumed traumatic background are only minimally responsive to
      these stress management procedures. The authors propose hypnotically induced
      dissociative strategies as a model of intervention for this category of dental
      phobic patients. The proposed model can help reduce or even suspend symptomatic
      behavior during dental treatment.

PMID- 24568325
TI  - Posthypnotic use of olfactory stimulus for pain management.
AB  - Chronic pain due to disease or injury persists even after interventions to
      alleviate these conditions. Opiates are not always effective for the patient and
      have undesirable side effects. Hypnosis has been shown to be an effective
      treatment and may be enhanced by the use of olfactory stimulation as a
      posthypnotic cue. The article details 2 case reports that demonstrate the
      possible benefits of olfactory stimulus as an adjunct to hypnosis for pain
      relief.

PMID- 24568326
TI  - Attachment and suggestion-related phenomena.
AB  - This study uses a new classification of suggestion-related phenomena and
      investigates the relationship between attachment styles and reaction to
      suggestion. The authors used 3 traditional experimental tasks: a stimulus
      misinformation task, an inkblot perception task, and a subjective estimation of a
      nonexistent difference task. A measure of adult attachment was also taken.
      Participants with a high attachment insecurity as opposed to those with a low one
      were less influenced by suggestions in the recall phase of the memory task.
      Results are discussed within the framework of suggestion models, the dual models
      of social behavior, and the adult attachment model. Implications of findings are
      limited to simple suggestion rather than the more complex set of responses
      related to hypnotizability.

PMID- 24568320
TI  - Analysis of the co-operative interaction between the allosterically regulated
      proteins GK and GKRP using tryptophan fluorescence.
AB  - Hepatic glucose phosphorylation by GK (glucokinase) is regulated by GKRP (GK
      regulatory protein). GKRP forms a cytosolic complex with GK followed by nuclear
      import and storage, leading to inhibition of GK activity. This process is
      initiated by low glucose, but reversed nutritionally by high glucose and fructose
      or pharmacologically by GKAs (GK activators) and GKRPIs (GKRP inhibitors). To
      study the regulation of this process by glucose, fructose-phosphate esters and a
      GKA, we measured the TF (tryptophan fluorescence) of human WT (wild-type) and
      GKRP-P446L (a mutation associated with high serum triacylglycerol) in the
      presence of non-fluorescent GK with its tryptophan residues mutated. Titration of
      GKRP-WT by GK resulted in a sigmoidal increase in TF, suggesting co-operative
      PPIs (protein-protein interactions) perhaps due to the hysteretic nature of GK.
      The affinity of GK for GKRP was decreased and binding co-operativity increased by
      glucose, fructose 1-phosphate and GKA, reflecting disruption of the GK-GKRP
      complex. Similar studies with GKRP-P446L showed significantly different results
      compared with GKRP-WT, suggesting impairment of complex formation and nuclear
      storage. The results of the present TF-based biophysical analysis of PPIs between
      GK and GKRP suggest that hepatic glucose metabolism is regulated by a metabolite
      sensitive drug-responsive co-operative molecular switch, involving complex
      formation between these two allosterically regulated proteins.

PMID- 24568327
TI  - Hypnotherapy for persistent genital arousal disorder: a case study.
AB  - Persistent genital arousal disorder (PGAD) is characterized by intrusive sexual
      arousal that is unresolvable via sexual activity and persists for an extended
      period of time. PGAD's etiology is unknown, and it has no established treatments.
      This case study reports on a 71-year-old female patient diagnosed with PGAD who
      received 9 sessions of hypnotherapy. The following measures were administered at
      baseline and follow-up: Hospital Anxiety and Depression Scale, Center for
      Epidemiologic Studies Depression Scale, Pittsburgh Sleep Quality Index, and
      visual analogue measurements of quality of life, intensity of symptoms, and
      marital interference. At follow-up, there were significant improvements in all
      measures. Given the currently limited alternatives for treatment, this case study
      suggests that hypnotherapy may be beneficial for some patients with PGAD.

PMID- 24568328
TI  - Efficacy of combined cognitive-behavior therapy and hypnotherapy in anorexia
      nervosa: a case study.
AB  - A 22-year-old female diagnosed with anorexia nervosa received brief psychotherapy
      within a span of 1.5 months. Detailed cognitive-behavioral assessment was done
      and eating attitude was rated. Intervention of eating behavior and cognitive
      restructuring were initiated along with regular practice of self-hypnosis with
      ego-strengthening suggestions. Age regression was done to identify conflicts.
      Significant improvement in eating attitude was noted after 8 sessions without
      relapse at 3 months. Details of the psychotherapy are discussed.

PMID- 24568329
TI  - A causal model explaining the relationships governing beliefs, attitudes, and
      hypnotic responsiveness.
AB  - The author developed a new scale aimed at measuring beliefs about "hypnotic
      states" and investigated the influence of such beliefs and attitudes on hypnotic
      responses in a large sample of Japanese undergraduate students. Exploratory
      factor analysis of this new questionnaire examining beliefs about hypnotic states
      yielded four factors: Dissociative or Depersonalized Experience, Loss of Self
      Control, Therapeutic Expectation, and Arousing Extraordinary Ability. The results
      of structural equation modeling showed that Therapeutic Expectation and Arousing
      Extraordinary Ability influenced hypnotizability through attitudes toward
      hypnosis, while also directly affecting subjective experiences without mediating
      attitudes. Present findings suggest that it is more effective to enhance
      therapeutic expectations than to correct misconceptions about hypnotic states in
      modification of patients' beliefs before initiating treatment.

PMID- 24568331
TI  - [Separation of amino acid enantiomers by high performance liquid chromatography].
AB  - Enantiomeric forms of the target analytes can be separated using chiral
      stationary phases based on cyclodextrins, macrocyclic polyethers and antibiotics,
      and derivatized polysaccharides and cyclofructans. The polar-organic, reverse
      phase and normal-phase separation system of the mobile phase can be used for
      chromatographic separation of racemic mixtures of amino acids, depending on the
      type of the chiral stationary phase. In addition to the direct method of
      separation, the possibility of derivatization with a chiral derivatization agent
      is used. The conventional detection techniques, circular dichroism and laser
      polarimetry detection can be used to detect amino acids after HPLC separation.

PMID- 24568332
TI  - [Where does the development of new antituberculotics go? Part 2 - in vitro
      evaluation].
AB  - The present paper is a continuation of a publication of 2012 (Ces. a slov. Farm.
      2012; 31, 150-158). It is oriented at the evaluation of potential
      antituberculotics in vitro, which is the most widely used approach to testing.
      The paper is based on the information from Chemical Abstracts 2011-2013. It is a
      selection from nearly three thousand items of information intended to help
      researchers. The greatest attention is paid to the multiresistant strains of
      Mycobacterium tuberculosis. In vitro evaluation for the development of new drugs
      is of great importance, but it is just the first stretch of the road to new
      medicinal drugs.

PMID- 24568330
TI  - Effects of hyperbaric oxygen on the osteogenic differentiation of mesenchymal
      stem cells.
AB  - BACKGROUND: Hyperbaric oxygenation was shown to increase bone healing in a rabbit
      model. However, little is known about the regulatory factors and molecular
      mechanism involved.We hypothesized that the effect of hyperbaric oxygen (HBO) on
      bone formation is mediated via increases in the osteogenic differentiation of
      mesenchymal stem cells (MSCs) which are regulated by Wnt signaling. METHODS: The
      phenotypic characterization of the MSCs was analyzed by flow cytometric analysis.
      To investigate the effects of HBO on Wnt signaling and osteogenic differentiation
      of MSCs, mRNA and protein levels of Wnt3a, beta-catenin, GSK-3beta, Runx 2, as
      well as alkaline phosphatase activity, calcium deposition, and the intensity of
      von Kossa staining were analyzed after HBO treatment. To investigate the effects
      of HBO on Wnt processing and secretion, the expression of Wntless and vacuolar
      ATPases were quantified after HBO treatment. RESULTS: Cells expressed MSC markers
      such as CD105, CD146, and STRO-1. The mRNA and protein levels of Wnt3a, beta
      catenin, and Runx 2 were up-regulated, while GSK-3beta was down-regulated after
      HBO treatment. Western blot analysis showed an increased beta-catenin
      translocation with a subsequent stimulation of the expression of target genes
      after HBO treatment. The above observation was confirmed by small interfering
      (si)RNA treatment. HBO significantly increased alkaline phosphatase activity,
      calcium deposition, and the intensity of von Kossa staining of osteogenically
      differentiated MSCs. We further showed that HBO treatment increased the
      expression of Wntless, a retromer trafficking protein, and vacuolar ATPases to
      stimulate Wnt processing and secretion, and the effect was confirmed by siRNA
      treatment. CONCLUSIONS: HBO treatment increased osteogenic differentiation of
      MSCs via regulating Wnt processing, secretion, and signaling.

PMID- 24568333
TI  - Production of flavonoids and isoflavonoids in jasmonic acid-induced red clover
      suspension cultures.
AB  - Effect of exogenously applied jasmonic acid (JA) in combination with calcium and
      verapamil (a calcium channels blocker) on the production of flavonoids and
      isoflavonoids in suspension cultures of Trifolium pratense L. was investigated.
      The culture was cultivated in Gamborg medium with an addition of 2 mg.l(-1) of
      2,4-dichlorophenoxyacetic acid and 2 mg.l(-1) of 6-benzylaminopurine, at the
      temperature of 25  degrees C, 16-hr light/8-hr dark period. The best effect of
      jasmonic acid on the production of flavonoids and isoflavonoids was manifested
      after a 24-hour application of the 50 MUmol.l(-1) concentration. The maximum
      production of JA-induced suspension culture was observed when cells were treated
      with a high level of calcium (10 mmol.l(-1)). The addition of all concentrations
      of verapamil to JA-induced suspension culture decreased production of flavonoids
      and isoflavonoids.

PMID- 24568334
TI  - [Study of local anaesthetics: part 204* determination of critical micelle
      concentrations of selected derivatives of pyrrolidino-m-alkoxyphenylcarbamic acid
      using pyrene as a probe].
AB  - The critical micelle concentrations of the studied derivatives of pyrrolidino-m
      alkoxyphenylcarbamic acid in aqueous media at 25  degrees C were determined using
      the UV/VIS absorption spectroscopy method with pyrene as a probe. In the
      absorption spectra of the derivatives and pyrene, there were examined unmasked
      pyrene peaks, at wavelength of 336 and 320 nm for VIII Z, XIV Z and XVII Z, and
      in addition at 308 nm for XXIX Z. The critical micelle concentrations were
      defined from the plots of the sum of the unmasked pyrene peaks against the
      surfactant concentration that had a sigmoidal character of Boltzmann type. The
      cmc values of the derivatives were exponentially dependent on the number of
      carbons in the hydrophobic chain. From the plot of ln (cmc) against the number of
      carbons n with the equation ln (cmc) = -0.146-0.691n, the value of the Gibbs free
      energy of transfer of each methylene group of the alkoxychain from the aqueous
      phase into the internal hydrophobic volume of micelle was also defined:
      deltaDeltaG(CH(2)) = (-0.691 +/- 0.023)RT. Building on the obtained results, the
      spherical micelle forming in the solution can be assumed.

PMID- 24568335
TI  - Inhibition of 12/15 lipoxygenase by curcumin and an extract from Curcuma longa L.
AB  - Curcumin (diferuloylmethane) is an orange-yellow secondary metabolic compound
      from the rhizome of turmeric (Curcuma longa L.), a spice often found in curry
      powder. It is one of the major curcuminoids of turmeric. For centuries, curcumin
      has been used in some medicinal preparations or as a food colouring agent. A
      variety of enzymes that are closely associated with inflammation and cancer were
      found to be modulated by curcumin. This paper summarized the results of the
      inhibitory effect of curcumin and a Curcuma longa L. ethanolic extract on
      lipoxygenase from the rat lung cytosolic fraction. The positional specificity
      determination of arachidonic acid dioxygenation by RP- and SP-HPLC methods showed
      that in a purified enzyme preparation from the rat lung cytosol the specific form
      of lipoxygenase (LOX) is present exhibiting 12/15-LOX dual specificity (with
      predominant 15-LOX activity). The inhibitory activity of curcumin and Curcuma
      longa extract on LOX from cytosolic fraction of rat lung was expressed in the
      percentage of inhibition and as IC50. Lineweaver-Burk plot analysis has indicated
      that curcumin is the competitive inhibitor of 12/15 LOX from the rat lung
      cytosolic fraction.

PMID- 24568336
TI  - [Identifying and solving drug-related problems in terms of the community
      pharmacist].
AB  - The issue of drug related problems (DRPs) has been known and dealt with in many
      studies for a long time. It is primarily due to the fact that drug-related
      problems have the potential to increase patients morbidity and mortality in
      particular. The issue of identifying and solving drug-related problems in the
      area of pharmacotherapy by community pharmacists in the Slovak Republic, unlike
      in other European countries such as the Netherlands and the United Kingdom, is
      still at the beginning and gradually developing. The aim of the survey was to
      obtain information from pharmacy practice concerning the current state and
      possible solutions of potential risks of medicines in the form of drug-related
      problems of patients from community pharmacists point of view as well as to find
      out the role and status of community pharmacists in identifying and solving drug
      related problems. A questionnaire survey using a sample of 237 respondents, its
      statistical processing and evaluation revealed the drug-related problems
      frequency met at their patients (the most common types of DRPs, their causes and
      subsequent intervention), as well as the opinions of community pharmacists on
      their current possibilities of (legislative, material, personnel, time) solving
      and risk-rating therapies for patients.

PMID- 24568337
TI  - [Globalization and its impact on pharmacy services in the Slovak Republic].
AB  - Public pharmacies are excellent medical facilities having the largest number of
      contacts with patients. They are the facilities of the first and last contact
      with the health care system for the patient. Public pharmacies are unique and
      easily accessible places in the health care system with a high proficiency in the
      provision of pharmaceutical care and highly qualified medical staff. The aim of
      this paper was to determine geographical-demographic situation, the legal form of
      the ownership of public pharmacies, and the owner share of pharmacists on the
      capital of public pharmacies in Slovakia. The number on of providers of
      pharmaceutical care depends on the population at the level of regions, districts,
      towns and villages with differing tightness of binding. The most common legal
      form of the provider of pharmaceutical care in Slovakia in public pharmacies were
      limited companies with 73.6% share, a sole proprietor - pharmacist had 23.9%, and
      public limited companies had 1.3%. In the branches of public pharmacies the
      limited companies had 73.4% share, a sole proprietor - pharmacist had 26%, public
      limited companies had 1%. The owner share of the pharmacist on the capital in
      public pharmacies was 50.4%, and in the branches of public pharmacies it was 66%,
      owned by a sole proprietor or limited company.

PMID- 24568339
TI  - Response to letter of Pollock, Hassan and Smith, "Diagnostic confusion in
      periorbital necrotising fasciitis".

PMID- 24568338
TI  - Enhancing targeted tumor treatment by near IR light-activatable photodynamic
      photothermal synergistic therapy.
AB  - For several decades, cancer has been one of the most life-threatening diseases.
      For enhancing anticancer efficiency with minimum side effects, combination
      therapy is envisioned. The current manuscript reports for the first time the
      development of a methylene blue (MB) bound nanoplatform, which is capable of
      delivering targeted diagnostic and combined synergistic photothermal and
      photodynamic treatment of cancer. Experimental data found that, once the
      nanoparticle binds with the target cell surface, it can detect LNCaP human
      prostate cancer cell selectively using fluorescence imaging. Our result shows
      that the therapeutic actions can be controlled with external NIR light. No
      cytotoxicity was observed in the absence of NIR light. Targeted photodynamic and
      photothermal treatment using 785 nm NIR light indicates that the multimodal
      treatment enhances the possibility of destroying LNCaP prostate cancer cells in
      vitro dramatically. We discuss the operating principle for the targeted imaging
      and possible mechanisms for combined therapeutic actions. Our experimental data
      show that NIR light activated combined therapy for cancer may become a highly
      effective treatment procedure in clinical settings. 

PMID- 24568340
TI  - A new sesquiterpenoid from Scaphium macropodum (Miq.) Beumee.
AB  - A new sesquiterpenoid, malayscaphiol (1), and three known compounds, lupeol (2),
      lupenone (3) and stigmasterol (4), were isolated from the methanolic extract of
      the stem bark of Scaphium macropodum. The structures of the isolated compounds
      were determined using several spectroscopic methods, including UV-vis, FT-IR, 1D
      and 2D NMR, and mass spectrometer. Major isolated compounds were assayed for
      cytotoxicity and anti-acetylcholinesterase activities. The chemotaxonomy
      significance of this plant was also discussed. 

PMID- 24568341
TI  - Dissecting the mechanism of histone deacetylase inhibitors to enhance the
      activity of zinc finger nucleases delivered by integrase-defective lentiviral
      vectors.
AB  - Integrase-defective lentiviral vectors (IDLVs) have been of limited success in
      the delivery of zinc finger nucleases (ZFNs) to human cells, due to low
      expression. A reason for reduced gene expression has been proposed to involve the
      epigenetic silencing of vector genomes, carried out primarily by histone
      deacetylases (HDACs). In this study, we tested valproic acid (VPA), a known HDAC
      inhibitor (HDACi), for its ability to increase transgene expression from IDLVs,
      especially in the context of ZFN delivery. Using ZFNs targeting the human
      adenosine deaminase (ADA) gene in K562 cells, we demonstrated that treatment with
      VPA enhanced ZFN expression by up to 3-fold, resulting in improved allelic
      disruption at the ADA locus. Furthermore, three other U.S. Food and Drug
      Administration-approved HDACis (vorinostat, givinostat, and trichostatin-A)
      exhibited a similar effect on the activity of ZFN-IDLVs in K562 cells. In primary
      human CD34(+) cells, VPA- and vorinostat-treated cells showed higher levels of
      expression of both green fluorescent protein (GFP) as well as ZFNs from IDLVs. A
      major mechanism for the effects of HDAC inhibitors on improving expression was
      from their modulation of the cell cycle, and the influence of
      heterochromatinization was determined to be a lesser contributing factor.

PMID- 24568344
TI  - How effective is [corrected] the use of DBS and DPS as tools to encourage
      widespread therapeutic drug monitoring?

PMID- 24568343
TI  - Patients in a private hospital in India leave the emergency department against
      medical advice for financial reasons.
AB  - BACKGROUND: Some reports indicate financial concerns as a factor affecting ED
      patients leaving the acute care setting against medical advice (AMA). In India,
      no person is supposed to be denied urgent care because of inability to pay. Since
      a large proportion of the Indian health care system is financed by out-of-pocket
      expenses, we investigate the role of financial constraints for ED patients at a
      private hospital in India in leaving AMA. METHODS: A prospective ED-based cross
      sectional survey of patients leaving AMA was conducted at a private hospital in
      India from 1 October 2010 to 31 December 2010. Descriptive statistics and the chi
      square test were used to identify associations between financial factors and the
      decision to leave the hospital AMA. RESULTS: Overall, 55 (3.84%) ED patients left
      AMA, of which 46 (84%) reported leaving because of financial restrictions. Thirty
      nine (71%) respondents indicated the medical bill would represent more that 25%
      of their annual income. Females (19/19) were more likely to leave AMA for
      financial reasons compared to males (27/36, p = 0.017). Among females who signed
      out AMA, the decision was never made by the female herself. CONCLUSION: The
      number of people leaving the ED AMA in a private Indian hospital is relatively
      high, with most leaving for financial reasons. In most cases, women did not
      decide to leave the ED AMA for themselves, whereas males did. This survey
      suggests that steps are needed to ensure that the inability to pay does not
      prevent emergent care from being provided.

PMID- 24568342
TI  - X-ray structural and biological evaluation of a series of potent and highly
      selective inhibitors of human coronavirus papain-like proteases.
AB  - Structure-guided design was used to generate a series of noncovalent inhibitors
      with nanomolar potency against the papain-like protease (PLpro) from the SARS
      coronavirus (CoV). A number of inhibitors exhibit antiviral activity against SARS
      CoV infected Vero E6 cells and broadened specificity toward the homologous PLP2
      enzyme from the human coronavirus NL63. Selectivity and cytotoxicity studies
      established a more than 100-fold preference for the coronaviral enzyme over
      homologous human deubiquitinating enzymes (DUBs), and no significant cytotoxicity
      in Vero E6 and HEK293 cell lines is observed. X-ray structural analyses of
      inhibitor-bound crystal structures revealed subtle differences between binding
      modes of the initial benzodioxolane lead (15g) and the most potent analogues 3k
      and 3j, featuring a monofluoro substitution at para and meta positions of the
      benzyl ring, respectively. Finally, the less lipophilic bis(amide) 3e and
      methoxypyridine 5c exhibit significantly improved metabolic stability and are
      viable candidates for advancing to in vivo studies. 

PMID- 24568345
TI  - New age of quick and onsite bioassays for forensics: where are we now?

PMID- 24568346
TI  - Study suggests blood test can accurately detect breast cancer.

PMID- 24568347
TI  - Cosmetic bioanalysis using LC-MS: challenges and future outlook.

PMID- 24568348
TI  - Common bioanalytical deficiencies with bioequivalence submissions in Abbreviated
      New Drug Applications.
AB  - BACKGROUND: The US FDA published A Guidance for Industry: Bioanalytical Method
      Validation in May 2001. Despite the publication of the guidance, companies
      continue to submit bioequivalence studies with bioanalytical deficiencies that
      preclude Abbreviated New Drug Application approval. The Divisions of
      Bioequivalence in the FDA's Office of Generic Drugs conducted a survey of the
      bioequivalence submissions over a 10-year period (2001-2011) to identify the most
      commonly occurring bioanalytical deficiencies. RESULTS: Data from a total of 4028
      Abbreviated New Drug Application submissions were collected to identify
      bioanalytical deficiencies. Of the three categories of bioanalytical deficiencies
      (method, validation and report), the majority of the deficiencies were from the
      bioanalytical method validation section. Globally, the percentage of
      bioanalytical method validation deficiencies was 62%. CONCLUSIONS: The approval
      of generic drugs would be accelerated if these deficiencies were avoided by
      generic companies by adhering to the guidance and therefore submitting a more
      complete application.

PMID- 24568349
TI  - Quantification of oligonucleotides by LC-MS/MS: the challenges of quantifying a
      phosphorothioate oligonucleotide and multiple metabolites.
AB  - BACKGROUND: LC-MS/MS allows quantification of therapeutic oligonucleotides in
      biological fluids at low ng/ml concentrations. Achieving selectivity between
      metabolites and parent molecules in a single assay is one of the biggest
      challenges when developing a method. We present a strategy that allows
      quantification of an 18-mer antisense therapeutic, trabedersen, and six
      metabolites in human plasma. RESULTS/METHODOLOGY: The method utilizes phenol
      chloroform and SPE with UHPLC-MS/MS to independently quantify trabedersen and the
      5'n-1, 5'n-2, 5'n-3, 3'n-1, 3'n-2 and 3'n-3 metabolites in a single assay. The
      qualification data indicate that if the method was validated it would meet
      regulatory expectations for precision, accuracy and selectivity. CONCLUSION: We
      show that quantification of an oligonucleotide and multiple metabolites,
      including isobaric 3' and 5' metabolites, is achievable in a single assay through
      good sample clean-up and careful optimization of the LC-MS/MS parameters. The
      strategy presented here can be applied elsewhere and may be useful for other
      oligonucleotides and their metabolites.

PMID- 24568351
TI  - A rapid multidimensional GC-flame-ionization detector method for determination of
      fatty acid methyl esters.
AB  - BACKGROUND: Fatty acids play important roles in the pathogenesis of many
      diseases. In order to investigate a wide spectrum of fatty acids in biological
      matrix, we developed an approach for quantitative analysis of fatty acids based
      on a heart-cutting 2D gas chromatographic-flame ionization detector system.
      RESULTS: This system uses a Dean Switch interface between the primary polar and
      secondary nonpolar capillary column. Most of the standards were separated by the
      primary column. Unresolved components are selectively transferred to the
      secondary column, where they are completely separated. This method was further
      evaluated using plasma obtained from 11 healthy and 11 chronic coronary artery
      disease patients. CONCLUSION: Our results prove that this approach is sensitive,
      precise and specific, capable of measuring 37 specific fatty acids. It indicates
      that this approach offers a reliable and sensitive technical platform for
      comprehensive quantification of fatty acids.

PMID- 24568350
TI  - Tus-Ter-lock immuno-PCR assays for the sensitive detection of tropomyosin
      specific IgE antibodies.
AB  - BACKGROUND: The increasing prevalence of food allergies requires development of
      specific and sensitive tests capable of identifying the allergen responsible for
      the disease. The development of serologic tests that can detect specific IgE
      antibodies to allergenic proteins would, therefore, be highly received. RESULTS:
      Here we present two new quantitative immuno-PCR assays for the sensitive
      detection of antibodies specific to the shrimp allergen tropomyosin. Both assays
      are based on the self-assembling Tus-Ter-lock protein-DNA conjugation system.
      Significantly elevated levels of tropomyosin-specific IgE were detected in sera
      from patients allergic to shrimp. CONCLUSION: This is the first time an
      allergenic protein has been fused with Tus to enable specific IgE antibody
      detection in human sera by quantitative immuno-PCR.

PMID- 24568352
TI  - Sensitivity-based analytical approaches to support human absolute bioavailability
      studies.
AB  - The characterization of absolute bioavailability (BA) is useful for non
      intravenous (iv.) formulations during drug development and is required by some
      health authorities. A study design of co-administrating an iv. isotopically
      labeled microdose with a therapeutic oral dose is a viable approach for the
      determination of human PK and has been accepted by regulatory agencies. The
      implementation of an iv.-microdose with oral therapeutic dose in absolute BA
      studies speeds up clinical development. In recent years, AMS to measure a
      radiolabeled microdose has been utilized to support several clinical absolute BA
      studies. An alternative approach for conducting microdose studies is using LC
      MS/MS alone to quantitate both the iv. drug and the oral drug. Because both
      labeled and unlabeled drugs can be measured simultaneously with LC-MS/MS, it is
      cost effective. However, for compounds with high volume of distribution and/or
      poor LC-MS/MS response, AMS still provides a superior LLOQ. In this Perspective,
      we discuss a paradigm for selecting either an LC-MS/MS or AMS-based approach for
      generating concentration data in absolute BA studies dependent on the required
      sensitivity.

PMID- 24568353
TI  - Regulatory perspective of bioanalysis from a clinical pharmacology reviewer
      standpoint: do you see what I see?
AB  - Clinical pharmacology plays an important role in drug development, including the
      evaluation of the drug's pharmacokinetics, pharmacodynamics, drug-interaction
      potential, exposure-response relationship and safety considerations when being
      used in specific populations. Clinical pharmacology data is pivotal in ensuring
      the delivery of the right drug, in the right dose, at the right time, to each
      particular patient and it has significantly influenced the risk/benefit
      assessment and labeling recommendations. Consequently, the reliability of the
      bioanalytical methods and data are of considerable importance, and the solid
      footing in drug development. Documentation of bioanalytical data from method
      validation or clinical trials is a critical element supporting regulatory
      submissions such as new drug applications or biologics license applications. Case
      examples are presented to highlight the utility and importance of bioanalysis in
      drug development to ensure that drug products are safe, efficacious, and given at
      the right dose.

PMID- 24568354
TI  - Stable isotope-labeling studies in metabolomics: new insights into structure and
      dynamics of metabolic networks.
AB  - The rapid emergence of metabolomics has enabled system-wide measurements of
      metabolites in various organisms. However, advances in the mechanistic
      understanding of metabolic networks remain limited, as most metabolomics studies
      cannot routinely provide accurate metabolite identification, absolute
      quantification and flux measurement. Stable isotope labeling offers opportunities
      to overcome these limitations. Here we describe some current approaches to stable
      isotope-labeled metabolomics and provide examples of the significant impact that
      these studies have had on our understanding of cellular metabolism. Furthermore,
      we discuss recently developed software solutions for the analysis of stable
      isotope-labeled metabolomics data and propose the bioinformatics solutions that
      will pave the way for the broader application and optimal interpretation of
      system-scale labeling studies in metabolomics.

PMID- 24568356
TI  - Lipidomics of Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a progressive brain disease that leads to an
      irreversible loss of neurons and cognition. It is the most common cause of
      dementia and can be considered as a major public health problem. At the
      histological level, AD is characterized by senile plaques and neurofibrillary
      tangles. Numerous studies involving genomic, transcriptomic and proteomic
      approaches have been published in order to understand the molecular mechanisms
      involved in AD, and to find new biomarkers. Metabolomics, and in particular
      lipidomics, have recently offered new possibilities due to the development of
      robust and sensitive analytical methods, such as LC-MS. This review aims to
      illustrate how lipidomics can help understand the biological mechanisms inherent
      to AD and how lipids can be considered as relevant biomarkers of AD at early
      stages.

PMID- 24568357
TI  - Top-down analytical platforms for the characterization of the human salivary
      proteome.
AB  - Comprehensive analysis and characterization of the human salivary proteome is an
      important step towards the possible use of saliva for diagnostic and prognostic
      purposes. The contribution of the different sources to whole saliva, and the
      evaluation of individual variability and physiological modifications have been
      investigated by top-down proteomic approaches, disclosing the faceted and complex
      profile of the human salivary proteome. All this information is essential to
      develop saliva protein biomarkers. In this Review the major results obtained in
      the field by top-down platforms, and the improvements required to allow a more
      complete picture, will be discussed.

PMID- 24568358
TI  - N-heterocyclic carbene catalyzed carba-, sulfa-, and phospha-Michael additions
      with NHC.CO2 adducts as precatalysts.
AB  - N-heterocyclic carbene catalyzed Michael additions have been revisited with 1,3
      dialkyl- or 1,3-diarylimidazol(in)ium-2-carboxylates, that is, NHC.CO2 adducts,
      as the source of the free NHC catalysts in solution. Using these precatalysts, a
      number of efficient carba-, sulfa-, and phospha-Michael additions were achieved
      very conveniently, without the need for an external strong base to generate the
      NHC by deprotonation of an azolium salt. To further expand the scope of the
      procedure, some NHC-catalyzed sulfa-Michael/aldol organocascades were also
      investigated. 

PMID- 24568359
TI  - Second harmonic generation from artificially stacked transition metal
      dichalcogenide twisted bilayers.
AB  - Optical second harmonic generation (SHG) is known as a sensitive probe to the
      crystalline symmetry of few-layer transition metal dichalcogenides (TMDs). Layer
      number dependent and polarization resolved SHG have been observed for the special
      case of Bernal stacked few-layer TMDs, but it remains largely unexplored for
      structures deviated from this ideal stacking order. Here we report on the SHG
      from homo- and heterostructural TMD bilayers formed by artificial stacking with
      an arbitrary stacking angle. The SHG from the twisted bilayers is a coherent
      superposition of the SH fields from the individual layers, with a phase
      difference depending on the stacking angle. Such an interference effect is
      insensitive to the constituent layered materials and thus applicable to hetero
      stacked bilayers. A proof-of-concept demonstration of using the SHG to probe the
      domain boundary and crystal polarity of mirror twins formed in chemically grown
      TMDs is also presented. We show here that the SHG is an efficient, sensitive, and
      nondestructive characterization for the stacking orientation, crystal polarity,
      and domain boundary of van der Waals heterostructures made of noncentrosymmetric
      layered materials. 

PMID- 24568355
TI  - Challenges and recent advances in mass spectrometric imaging of
      neurotransmitters.
AB  - Mass spectrometric imaging (MSI) is a powerful tool that grants the ability to
      investigate a broad mass range of molecules, from small molecules to large
      proteins, by creating detailed distribution maps of selected compounds. To date,
      MSI has demonstrated its versatility in the study of neurotransmitters and
      neuropeptides of different classes toward investigation of neurobiological
      functions and diseases. These studies have provided significant insight in
      neurobiology over the years and current technical advances are facilitating
      further improvements in this field. Herein, we briefly review new MSI studies of
      neurotransmitters, focusing specifically on the challenges and recent advances of
      MSI of neurotransmitters.

PMID- 24568361
TI  - Electret film-enhanced triboelectric nanogenerator matrix for self-powered
      instantaneous tactile imaging.
AB  - We report the first self-powered electronic skin that consists of light-emitting
      diode (LED) and triboelectric nanogenerator (TENG) arrays that can be utilized
      for spatially mapping applied instantaneous-touch events and tracking the
      movement location of the target object by recording the electroluminescent
      signals of the LEDs without external power sources. The electret film-based TENG
      can deliver an open-circuit voltage of about -1070 V, a short-circuit current
      density of 10 mA/m(2), and a power density of 288 mW/m(2) on an external load of
      100 MOmega. The LEDs can be turned on locally when the back surface of the active
      matrix is touched, and the intensity of the emitted light depends on the
      magnitude of the applied local pressure on the device. A constructed active
      matrix of the LED-TENG array (8 * 7 pixels) can achieve self-powered, visual, and
      high-resolution tactile sensing by recording the electroluminescent signals from
      all of the pixels, where the active size of each pixel can be decreased to 10
      mm(2). This work is a significant step forward in self-powered tactile-mapping
      visualization technology, with a wide range of potential applications in touchpad
      technology, personal signatures, smart wallpapers, robotics, and safety
      monitoring devices. 

PMID- 24568362
TI  - An Egyptian child with erythromelalgia responding to a new line of treatment: a
      case report and review of the literature.
AB  - INTRODUCTION: Erythromelalgia is a rare clinical syndrome characterized by
      episodic erythema, warmth and intense burning pain, which commonly involves the
      extremities. For those affected, this disorder may lead to significant long-term
      morbidity. Unfortunately, to date, no definitive therapy is available. This case
      report describes an Egyptian child with primary erythromelalgia that manifested
      at an early age and showed partial response to therapy with cetirizine
      hydrochloride. This anecdotal case report may have a diagnostic value for
      clinicians who have not seen this disorder. CASE PRESENTATION: A 34-month-old
      previously healthy right-handed Hamitic boy without any significant past medical
      history presented at the age of 2 years with episodic bilateral pain in his feet.
      His mother reported associated warmth and erythema localized to his feet that
      never extended beyond his ankle joints. This pain is triggered by exertion and/or
      warm temperature exposure and is relieved by cooling measures. The diagnosis of
      erythromelalgia was made based on the patient's medical history and a thorough
      physical examination during the episodes. No evidence of local or systemic
      infection was present. Other causes for the symptoms were excluded by a negative
      extensive diagnostic work-up. Our patient did not respond to ibuprofen
      (15mg/kg/dose) three times a day but partial improvement with the oral non
      sedating antihistaminic cetirizine hydrochloride (2.5mg/kg/once daily) was
      observed. When the child stopped cetirizine hydrochloride for 1 month as a test,
      the symptoms became aggravated and were relieved when cetirizine therapy was
      restarted. Cetirizine hydrochloride had not previously been reported to have this
      effect in children with erythromelalgia. CONCLUSIONS: Erythromelalgia is a
      clinical syndrome of which the etiology, diagnosis and management are
      controversial. We describe a case of a 34-month-old Egyptian child with primary
      erythromelalgia that manifested at an early age. We believe that this is the
      first Egyptian case report of this kind in the literature. Partial response of
      this patient to cetirizine hydrochloride may grant us a new clue to understanding
      this mysterious condition.

PMID- 24568360
TI  - The effect of obstructive sleep apnea and treatment with continuous positive
      airway pressure on stroke rehabilitation: rationale, design and methods of the
      TOROS study.
AB  - BACKGROUND: Obstructive sleep apnea is a common sleep disorder in stroke
      patients. Obstructive sleep apnea is associated with stroke severity and poor
      functional outcome. Continuous positive airway pressure seems to improve
      functional recovery in stroke rehabilitation. To date, the effect of continuous
      positive airway pressure on cognitive functioning in stroke patients is not well
      established. The current study will investigate the effectiveness of continuous
      positive airway pressure on both cognitive and functional outcomes in stroke
      patients with obstructive sleep apnea. METHODS/DESIGN: A randomized controlled
      trial will be conducted on the neurorehabilitation unit of Heliomare, a
      rehabilitation center in the Netherlands. Seventy stroke patients with
      obstructive sleep apnea will be randomly allocated to an intervention or control
      group (n = 2*35). The intervention will consist of four weeks of continuous
      positive airway pressure treatment. Patients allocated to the control group will
      receive four weeks of treatment as usual. Outcomes will be assessed at baseline,
      immediately after the intervention and at two-month follow-up.In a supplementary
      study, these 70 patients with obstructive sleep apnea will be compared to 70
      stroke patients without obstructive sleep apnea with respect to cognitive and
      functional status at rehabilitation admission. Additionally, the societal
      participation of both groups will be assessed at six months and one year after
      inclusion. DISCUSSION: This study will provide novel information on the effects
      of obstructive sleep apnea and its treatment with continuous positive airway
      pressure on rehabilitation outcomes after stroke. TRIAL REGISTRATION:  TRIAL
      REGISTRATION NUMBER: Dutch Trial Register NTR3412.

PMID- 24568363
TI  - IgG4-related lacrimal sac diverticulitis.
AB  - IgG4-related disease is characterized by elevated serum IgG4 and tissue
      infiltration by IgG4-positive plasma cells. We herein report a case of lacrimal
      sac diverticulitis with marked IgG4-positive plasma cell infiltration. An 89-year
      old woman presenting with right lower eyelid mass. Imaging modalities
      demonstrated a cystic orbital mass located beneath the globe and adjacent to
      enlarged lacrimal sac. Serological tests showed high IgG4 and normal IgG levels,
      measuring 242 and 1603 mg/dl, respectively. The orbital mass was surgically
      excised. Histologically, the excised tissue demonstrated marked inflammation with
      fibrosis surrounded by mononuclear epithelial cells. A variety of IgG and IgG4
      positive plasma cells infiltrated the stroma. This patient was diagnosed as an
      IgG4-related lacrimal sac diverticulitis, based on current diagnostic criteria of
      IgG4-related disease. It is likely that IgG4-related inflammation occurs in a
      lacrimal sac diverticulum, which should be considered a differential diagnosis in
      inferior orbital tumors.

PMID- 24568364
TI  - Laparoscopic resection of hepatocellular carcinoma: when, why, and how? A single
      center experience.
AB  - PURPOSE: The aim of this study was to evaluate short- and intermediate-term
      results of laparoscopic liver resection in selected patients with hepatocellular
      carcinoma (HCC). PATIENTS AND METHODS: Eighty-five patients with HCC were
      subjected to liver resection between February 2007 and January 2013. From these,
      30 (35.2%) were subjected to laparoscopic liver resection and were
      retrospectively analyzed. Special emphasis was given to the indication criteria
      and to surgical results. RESULTS: There were 21 males and 9 females with a mean
      age of 57.4 years. Patients were subjected to 10 nonanatomic and 20 anatomic
      resections. Two patients were subjected to hand-assisted procedures (right
      posterior sectionectomies); all other patients were subjected to totally
      laparoscopic procedures. Conversion to open surgery was necessary in 4 patients
      (13.3%). Postoperative complications were observed in 12 patients (40%), and the
      mortality rate was 3.3%. Mean overall survival was 29.8 months, with 3-year
      overall and disease-free survival rates of 76% and 58%, respectively.
      CONCLUSIONS: Laparoscopic treatment of selected patients with HCC is safe and
      feasible and can lead to good short- and intermediate-term results.

PMID- 24568366
TI  - Enzyme-responsive amphiphilic PEG-dendron hybrids and their assembly into smart
      micellar nanocarriers.
AB  - Enzyme-responsive micelles have great potential as drug delivery platforms due to
      the high selectivity of the activating enzymes. Here we report a highly modular
      design for the efficient and simple synthesis of amphiphilic block copolymers
      based on a linear hydrophilic polyethyleneglycol (PEG) and an enzyme-responsive
      hydrophobic dendron. These amphiphilic hybrids self-assemble in water into
      micellar nanocontainers that can disassemble and release encapsulated molecular
      cargo upon enzymatic activation. The utilization of monodisperse dendrons as the
      stimuli-responsive block enabled a detailed kinetic study of the molecular
      mechanism of the enzymatically triggered disassembly. The modularity of these PEG
      dendron hybrids allows control over the disassembly rate of the formed micelles
      by simply tuning the PEG length. Such smart amphiphilic hybrids could potentially
      be applied for the fabrication of nanocarriers with adjustable release rates for
      delivery applications. 

PMID- 24568367
TI  - Adverse drug reactions - preventable or unexpected?

PMID- 24568365
TI  - The SNAP trial: a double blind multi-center randomized controlled trial of a
      silicon nitride versus a PEEK cage in transforaminal lumbar interbody fusion in
      patients with symptomatic degenerative lumbar disc disorders: study protocol.
AB  - BACKGROUND: Polyetheretherketone (PEEK) cages have been widely used in the
      treatment of lumbar degenerative disc disorders, and show good clinical results.
      Still, complications such as subsidence and migration of the cage are frequently
      seen. A lack of osteointegration and fibrous tissues surrounding PEEK cages are
      held responsible. Ceramic implants made of silicon nitride show better
      biocompatible and osteoconductive qualities, and therefore are expected to lower
      complication rates and allow for better fusion.Purpose of this study is to show
      that fusion with the silicon nitride cage produces non-inferior results in
      outcome of the Roland Morris Disability Questionnaire at all follow-up time
      points as compared to the same procedure with PEEK cages. METHODS/DESIGN: This
      study is designed as a double blind multi-center randomized controlled trial with
      repeated measures analysis. 100 patients (18-75 years) presenting with
      symptomatic lumbar degenerative disorders unresponsive to at least 6 months of
      conservative treatment are included. Patients will be randomly assigned to a PEEK
      cage or a silicon nitride cage, and will undergo a transforaminal lumbar
      interbody fusion with pedicle screw fixation. Primary outcome measure is the
      functional improvement measured by the Roland Morris Disability Questionnaire.
      Secondary outcome parameters are the VAS leg, VAS back, SF-36, Likert scale,
      neurological outcome and radiographic assessment of fusion. After 1 year the
      fusion rate will be measured by radiograms and CT. Follow-up will be continued
      for 2 years. Patients and clinical observers who will perform the follow-up
      visits will be blinded for type of cage used during follow-up. Analyses of
      radiograms and CT will be performed independently by two experienced
      radiologists. DISCUSSION: In this study a PEEK cage will be compared with a
      silicon nitride cage in the treatment of symptomatic degenerative lumbar disc
      disorders. To our knowledge, this is the first randomized controlled trial in
      which the silicon nitride cage is compared with the PEEK cage in patients with
      symptomatic degenerative lumbar disc disorders. TRIAL REGISTRATION: NCT01557829.

PMID- 24568368
TI  - A case of akathisia induced by escitalopram: case report & review of literature.
AB  - Although cases of Selective Serotonin Reuptake Inhibitor (SSRI) induced akathisia
      have often been reported in literature, this adverse effect has not adequately
      been mentioned in major pharmacology textbooks. As a result, SSRIinduced
      akathisia is very frequently under-recognized. A review of literature showed that
      almost all frequently used SSRIs such as Fluvoxamine, Fluoxetine, Sertraline,
      Citalopram have been reported to be causing akathisia. SSRI-induced restless legs
      syndrome and movement disorders have also been reported. However, Escitalopram
      induced akathisia is rare. In our review of literature, we could find only one
      single case of Escitalopram-induced severe akathisia. And this specific SSRI drug
      has rarely been implicated with occurrence of restless legs syndrome and extra
      pyramidal side-effects like dytonia etc. Here, we present a case of Escitalopram
      induced severe akathisia - a 53year old female, who had developed severe
      akathisia after taking Escitalopram for a few days. According to the Barnes
      Akathisia Rating Scale (BARS), her Global Clinical Assessment of Akathisia Score
      was 5 i.e. severe akathisia. As per Naronjo Adverse Drug Reaction Scale the
      probability of association of this adverse reaction with Escitalopram was 7 (i.e.
      probable). Her symptoms continued in spite of prompt discontinuation of the drug.
      But, she improved rapidly with the use of Propranolol and Clonazepam. On the last
      follow-up, she was free from any symptoms. As new generation antidepressants are
      rarely associated with extra-pyramidal symptoms, the recognition of such adverse
      effects requires a high index of suspicion. Early recognition of the symptoms and
      discontinuation of the offending agent along with supportive therapy like a short
      course of benzodiazepines, beta-adrenergic antagonists or anticholinergics may
      rapidly relieve the patient from this distressing symptom. 

PMID- 24568371
TI  - Psychological models of suicide.
AB  - Suicidal behavior is highly complex and multifaceted. Consequent to the
      pioneering work of Durkheim and Freud, theoreticians have attempted to explain
      the biological, social, and psychological nature of suicide. The present work
      presents an overview and critical discussion of the most influential theoretical
      models of the psychological mechanisms underlying the development of suicidal
      behavior. All have been tested to varying degrees and have important implications
      for the development of therapeutic and preventive interventions. Broader and more
      in-depth approaches are still needed to further our understanding of suicidal
      phenomena.

PMID- 24568370
TI  - Edwardsiella tarda Hfq: impact on host infection and global protein expression.
AB  - Hfq is an RNA-binding protein that plays an important role in many cellular
      processes. In this study, we examined the biological effect of the Hfq of
      Edwardsiella tarda, a severe fish pathogen with a broad host range that includes
      humans. To facilitate the study, a markerless hfq in-frame deletion wild type,
      TXhfq, was constructed. Compared to the wild type TX01, TXhfq exhibited (i)
      retarded planktonic and biofilm growth, (ii) decreased resistance against
      oxidative stress, (iii) attenuated overall virulence and tissue dissemination and
      colonization capacity, (iv) impaired ability to replicate in host macrophages and
      to block host immune response. Introduction of a trans-expressed hfq gene into
      TXhfq restored the lost virulence of TXhfq. To identify potential Hfq targets,
      comparative global proteomic analysis was conducted, which revealed that 20
      proteins belonging to different functional categories were differentially
      expressed in TXhfq and TX01. Quantitative real time RT-PCR analysis showed that
      the mRNA levels of two thirds of the genes of the identified proteins were
      consistent with the proteomic results. Since TXhfq is dramatically attenuated in
      virulence, we further examined its potential as a naturally delivered vaccine
      administered via the immersion route in a flounder model. The results showed that
      TXhfq induced effective protection against lethal E. tarda challenge. Taken
      together, our study indicated that Hfq is required for the normal operation of E.
      tarda in multiple aspects, and that Hfq probably exerts a regulatory effect on a
      wide range of target genes at both transcription and post-transcription levels.

PMID- 24568369
TI  - Acetyl-lysine binding site of bromodomain-containing protein 4 (BRD4) interacts
      with diverse kinase inhibitors.
AB  - Members of the bromodomain and extra terminal (BET) family of proteins are
      essential for the recognition of acetylated lysine (KAc) residues in histones and
      have emerged as promising drug targets in cancer, inflammation, and contraception
      research. In co-crystallization screening campaigns using the first bromodomain
      of BRD4 (BRD4-1) against kinase inhibitor libraries, we identified and
      characterized 14 kinase inhibitors (10 distinct chemical scaffolds) as ligands of
      the KAc binding site. Among these, the PLK1 inhibitor BI2536 and the JAK2
      inhibitor TG101209 displayed strongest inhibitory potential against BRD4 (IC50=25
      nM and 130 nM, respectively) and high selectivity for BET bromodomains.
      Comparative structural analysis revealed markedly different binding modes of
      kinase hinge-binding scaffolds in the KAc binding site, suggesting that BET
      proteins are potential off-targets of diverse kinase inhibitors. Combined, these
      findings provide a new structural framework for the rational design of next
      generation BET-selective and dual-activity BET-kinase inhibitors.

PMID- 24568372
TI  - Synthesis and multitarget biological profiling of a novel family of rhein
      derivatives as disease-modifying anti-Alzheimer agents.
AB  - We have synthesized a family of rhein-huprine hybrids to hit several key targets
      for Alzheimer's disease. Biological screening performed in vitro and in
      Escherichia coli cells has shown that these hybrids exhibit potent inhibitory
      activities against human acetylcholinesterase, butyrylcholinesterase, and BACE-1,
      dual Abeta42 and tau antiaggregating activity, and brain permeability. Ex vivo
      studies with the leads (+)- and (-)-7e in brain slices of C57bl6 mice have
      revealed that they efficiently protect against the Abeta-induced synaptic
      dysfunction, preventing the loss of synaptic proteins and/or have a positive
      effect on the induction of long-term potentiation. In vivo studies in APP-PS1
      transgenic mice treated ip for 4 weeks with (+)- and (-)-7e have shown a central
      soluble Abeta lowering effect, accompanied by an increase in the levels of mature
      amyloid precursor protein (APP). Thus, (+)- and (-)-7e emerge as very promising
      disease-modifying anti-Alzheimer drug candidates. 

PMID- 24568375
TI  - There's still time to make a pledge for Change Day.
AB  - Last Saturday was World Thinking Day, the next couple of weeks have been
      designated Fairtrade Fortnight and celebrations are planned throughout March to
      mark National Bed Month. Staff in marketing departments across the land spend
      their lives dreaming up such awareness days, weeks and months, to the point where
      every day we are asked to think about something different. 

PMID- 24568374
TI  - Clustering of unhealthy lifestyle behaviors is associated with a low adherence to
      recommended preventive practices among COPD patients in Spain.
AB  - AIMS: To analyze clustering of unhealthy lifestyle behavior and its relationship
      with non-adherence to recommended clinical preventive care services among Spanish
      COPD patients. METHODS: Cross-sectional study including 2,575 COPD subjects from
      the 2006 Spanish National Health Survey (NHS) and 2009 European Health Survey for
      Spain (EHISS). Subjects were asked about the following recommended preventive
      practices: uptake of blood pressure (BP) measurement, lipid profile, influenza
      vaccination and dental examination. Lifestyle behaviors included: smoking status,
      physical activity, alcohol consumption and obesity. Logistic regression models
      were built to assess the association between clustering of unhealthy lifestyle
      and the uptake of preventive activities. RESULTS: Blood pressure measurement in
      the previous 6 months and a blood lipid test in the last year had not been taken
      by 11.74% and 23.26% of the subjects, respectively, in 2006 NHS and by 11.16% and
      16.33% of the subjects, respectively, in EHISS 2009. Then, 36.36% percent had not
      been vaccinated and 70.61% had not received dental examination in 2006 NHS and
      these percentages decreased to 27.33% and 66.22%, respectively, in 2009 EHISS. A
      higher number of unhealthy lifestyle behaviors increased the probability of not
      being vaccinated and not having a dental examination. Clustering of unhealthy
      lifestyle behaviors is linearly associated with a greater number of preventive
      measures unfulfilled. CONCLUSIONS: Compliance with healthy lifestyles and
      adherence to recommended clinical preventive services is under desirable levels
      among Spanish COPD patients. Patients with lifestyles considered as "worse" are
      those who also have lower uptake of recommended preventive activities.

PMID- 24568380
TI  - New batch of potential nurses joining HCA pilot scheme.
AB  - The number of aspiring nurses being recruited for a national training pilot is
      due to almost double next month. 

PMID- 24568376
TI  - The hospital-wide smoking ban is too difficult to enforce, trusts find.
AB  - Trusts are refusing to impose blanket bans on smoking in hospital grounds because
      they believe the policy would be unenforceable, despite government guidance that
      all hospitals should outlaw smoking completely. 

PMID- 24568381
TI  - Hundreds continue to practise despite lapsed NMC registrations.
AB  - More than 660 nurses have broken the law in the past two years by practising even
      though their registration has lapsed, according to the Nursing and Midwifery
      Council. 

PMID- 24568373
TI  - Differential localization of G protein betagamma subunits.
AB  - G protein betagamma subunits play essential roles in regulating cellular
      signaling cascades, yet little is known about their distribution in tissues or
      their subcellular localization. While previous studies have suggested specific
      isoforms may exhibit a wide range of distributions throughout the central nervous
      system, a thorough investigation of the expression patterns of both Gbeta and
      Ggamma isoforms within subcellular fractions has not been conducted. To address
      this, we applied a targeted proteomics approach known as multiple-reaction
      monitoring to analyze localization patterns of Gbeta and Ggamma isoforms in pre-
      and postsynaptic fractions isolated from cortex, cerebellum, hippocampus, and
      striatum. Particular Gbeta and Ggamma subunits were found to exhibit distinct
      regional and subcellular localization patterns throughout the brain. Significant
      differences in subcellular localization between pre- and postsynaptic fractions
      were observed within the striatum for most Gbeta and Ggamma isoforms, while
      others exhibited completely unique expression patterns in all four brain regions
      examined. Such differences are a prerequisite for understanding roles of
      individual subunits in regulating specific signaling pathways throughout the
      central nervous system. 

PMID- 24568383
TI  - Nurses are in 'perfect place' to offer psychological therapy to patients.
AB  - Intensive care nurses will receive training in psychological therapy in a
      landmark venture to help patients who experience hallucinations, delusions and
      panic attacks. 

PMID- 24568389
TI  - Health visitors unable to provide children's named person service.
AB  - New legislation that requires health boards to provide every pre-school child
      with a health visitor responsible for their care could fail because of a
      shortfall of hundreds of professionals. 

PMID- 24568392
TI  - RCN signs up to '999 plan' aimed at improving delivery of crisis care.
AB  - The RCN is one of 22 organisations to have signed a national agreement on
      improving co-operation between the NHS and the police on the care of people in a
      mental health crisis. 

PMID- 24568393
TI  - Nurses in successful trusts helping 'special measures' hospitals improve.
AB  - A record number of trusts were placed in special measures last year in what
      health secretary Jeremy Hunt has described as the worst year in the NHS's 65-year
      history. 

PMID- 24568399
TI  - Prostate cancer.
AB  - Essential facts Prostate cancer is the most common cancer in men and makes up 26
      per cent of all male cancer diagnoses in the UK. According to the charity
      Prostate Cancer UK, more than 40,000 men are diagnosed with the disease every
      year. However, prostate cancer can be slow growing and many men have a cancer
      that will not cause them harm in their lifetime, says the National Institute for
      Health and Care Excellence (NICE). 

PMID- 24568400
TI  - Delivering digitally: midwives in Bradford are making the move to electronic
      records.
AB  - Staff at Bradford Teaching Hospitals NHS Foundation Trust will begin the switch
      from paper to electronic records for expectant mothers this month. The change
      will allow women to access up to date records wherever it suits them and will
      free midwives from time-consuming from filling.

PMID- 24568402
TI  - All in a day's work An innovative one-stop clinic is keeping frail older people
      out of hospital.
AB  - A rapid access service for frail older is improving the care they receive and
      preventing hospital admissions by providing comprehensive assessment and
      diagnostic tests in one clinic setting. The multidisciplinary team can usually
      organise packages of health and social care that enable patients to return home.

PMID- 24568401
TI  - Make the pledge.
AB  - The first NHS Change Day in 2013, began with a Twitter conservation between
      clinicians. This year's March 3 event aims to attract 5000.000 pledges. The day
      harnesses individuals' passion for the NHS using voluntary commitments to
      implement (mostly) small, simple measures.

PMID- 24568423
TI  - Diagnosis and treatment of adults with scalp psoriasis.
AB  - Psoriasis is a chronic, lifelong skin condition, and scalp psoriasis is a common
      manifestation of this condition. Scalp psoriasis often requires separate
      treatment to psoriasis on other areas of the body because of the presence of
      hair, thinness of the skin and the visibility of this area, which may affect the
      person's quality of life and wellbeing. An increased understanding of the
      treatment options available for scalp psoriasis, management protocols and
      effective application techniques may result in improved outcomes for patients. 

PMID- 24568424
TI  - Developing good practice for clinical research nurses.
AB  - This article outlines the role of clinical research in the UK government's
      strategy for economic growth and the role of clinical research nurses in that
      research. The diverse skills and knowledge required by clinical research nurses
      to support a range of research studies in a number of research environments are
      described. The development and aim of the UK Clinical Research Facility Network
      is discussed, with particular focus on the role of the UK Clinical Research
      Facility Network Education Group in supporting clinical research nurses and
      research teams to acquire and maintain relevant research skills. The outcomes
      delivered by the UK Clinical Research Facility Network Education Group are
      outlined along with ongoing and future work. Recommendations to ensure that the
      workforce will be skilled appropriately to support future clinical research are
      provided. 

PMID- 24568425
TI  - Avoiding plagiarism: guidance for nursing students.
AB  - The pressures of study, diversity of source materials, past assumptions relating
      to good writing practice, ambiguous writing guidance on best practice and
      students' insecurity about their reasoning ability, can lead to plagiarism. With
      the use of source checking software, there is an increased chance that
      plagiarised work will be identified and investigated, and penalties given. In
      extreme cases, plagiarised work may be reported to the Nursing and Midwifery
      Council and professional as well as academic penalties may apply. This article
      provides information on how students can avoid plagiarism when preparing their
      coursework for submission. 

PMID- 24568426
TI  - Topical treatments.
AB  - I was interested in reading the article because, in the course of my work, I
      often see children who have developed eczema or other distressing skin diseases. 

PMID- 24568427
TI  - Two-way development.
AB  - When I first started working as a Voluntary Service Overseas (VSO) nurse lecturer
      in Malawi, where the focus of health care is often a lack of resources and staff
      shortages, I realised how important it was for care to be apparent in every
      patient encounter. 

PMID- 24568430
TI  - Support for family carers.
AB  - It is estimated that by 2037 there will be more than nine million family carers
      in the UK. Many will be looking after children and older relatives, and some will
      be getting older themselves. 

PMID- 24568428
TI  - How to progress your career.
AB  - If your job is losing its sparkle, it could be time to think about other options.
      But how do you weigh up whether a move will result in career development or a
      dead end? 

PMID- 24568431
TI  - Student life - aiming to go the extra smile.
AB  - NHS Change Day on March 3 will be another milestone in the eventful life of
      nursing student Ellie Milner. 

PMID- 24568433
TI  - Investment in a career pathway.
AB  - Initiatives at Kettering General Hospital NHS Foundation Trust are ensuring
      greater investment in the unregistered care workforce. 

PMID- 24568436
TI  - Small steps with big results.
AB  - March 3 marks the second NHS Change Day, which aims to inspire and encourage
      staff and the public to pledge to do something to improve care. 

PMID- 24568437
TI  - Chest infection helped me see patients' view.
AB  - The weeks leading up to Christmas are always full of warmth and excitement, plans
      to see loved ones and thinking up gift ideas. But it is also a time of hard work
      when overtime is often necessary. 

PMID- 24568438
TI  - Forensic support.
AB  - Sexual assault referral centres provide a dedicated service to people who have
      been raped or assaulted. 

PMID- 24568440
TI  - Blood glucose checks.
AB  - Measuring blood glucose in patients with diabetes by taking a sample of capillary
      blood is a safe method. It is also good for detecting hypoglycaemia or
      hyperglycaemia, and managing complications of diabetes. 

PMID- 24568442
TI  - A new index of abdominal obesity which effectively predicts risk of colon tumor
      development in female Japanese.
AB  - BACKGROUND: A relation between abdominal obesity and colorectal tumor development
      has been reported repeatedly, and is believed to be more remarkable in man than
      in women. However, the details vary depending on scientific reports. This may be
      due at least partly to the selected surface anthropometric index in addition to
      the influence of gender and ethnic groups. To cope with this, we considered a new
      index of abdominal obesity and evaluated its risk prediction potential. MATERIALS
      AND METHODS: Six hundred ninety five Japanese (262 women and 433 men) who had a
      colonoscopy were studied. The new index was named as waist circumference to
      height index (WHI) and was calculated by the formula of waist circumference
      (cm)/height (m)/height (m). Biochemical and lifestyle factors were investigated
      preceding the colonoscopy. Statistical analysis was performed using SPSS for
      Windows. RESULTS: Increase of WHI was associated with altered metabolism of
      carbohydrate and lipid in both women and men. WHI was positively related with the
      development of colon tumor of women, while not with that of men. Logistic
      regression analysis performed for stratified age groups (45-54, 55-64 and 65-74
      years) showed that WHI significantly increased odds ratio to 1.31 (CI 1.05-1.64
      p=0.01) in women of 55-65 years. In contrast, in men this index WHI reduced the
      odds ratio insignificantly, while low density lipoprotein and triglyceride
      significantly increased the odds ratio to 1.01 (CI 1.00-1.03 p=0.02) in the 55-65
      year group and to 1.02 (CI 1.00-1.03 p=0.02) in the 45-55 year group.
      CONCLUSIONS: In Japanese the risk factors for colon tumor development are
      different between women and men. WHI is a simple and efficient predictor of colon
      tumor risk in Japanese women and may be used to select those who should have
      colonoscopy.

PMID- 24568443
TI  - Increasing frequency of soft tissue sarcomas in Vojvodina - comparison with the
      literature.
AB  - BACKGROUND: Soft tissue sarcomas (STS) represent 1% of all malignant lesions. In
      this study the authors analyzed the incidence of STS in Vojvodina (the north
      region of Serbia) in the period from 1985 to 2009. A number of studies conducted
      worldwide indicate that STS incidence rates are tending to increase. MATERIALS
      AND METHODS: On the basis of data from the Cancer Registry of Vojvodina, age
      standardized STS incidence rates were established as well as their linear trend,
      with data on histological structure, age, gender and STS distribution at specific
      locations. RESULTS: The total number of registered patients was 1,308. Average
      age standardized rate was 1.90/100,000 per year. The investigated period showed a
      slight increase in the incidence rate (average annual percent increase=0.77%).
      The most frequent histological type was sarcoma not otherwise specified-NOS
      (27%), followed by leiomyosarcoma (21%), liposarcoma (14%), rhabdomyosarcoma
      (11%) and malignant fibrous histiocytoma (9%). The male/female ratio was 0.73:1.
      Every fifth patient was younger than 39. CONCLUSIONS: Comparison among eight
      international STS epidemiology studies show that the incidence rate range is
      between 1.4/100,000-5.0/100,000, though our finding is closer to the lower limit.
      Furthermore, the incidence rate increase was lower than that characteristic for
      the half of the analyzed studies. A partial explanation for that should be looked
      for among changes in diagnostic criteria and STS classifications.

PMID- 24568444
TI  - Diagnostic value of rectal bleeding in predicting colorectal cancer: a systematic
      review.
AB  - This study aimed at summarizing published study findings on the diagnostic value
      of rectal bleeding (RB) and informing clinical practice, preventive interventions
      and future research areas. We searched Medline and Embase for studies published
      by September 13, 2013 examining the risk of colorectal cancer in patients with RB
      using highly inclusive algorithms. Data for sensitivity, specificity, positive
      likelihood ratio, negative likelihood ratio and positive predictive value (PPV)
      of RB were extracted by two researchers and analyzed applying Meta-Disc (version
      1.4) and Stata (version 11.0). Methodological quality of studies was assessed
      according to QUADAS. A total of 38 studies containing 5,626 colorectal cancer
      patients and 73,174 participants with RB were included. The pooled sensitivity
      and specificity were 0.47 (95% CI: 0.45-0.48) and 0.96 (95% CI: 0.96-0.96)
      respectively. The overall PPVs ranged from 0.01 to 0.21 with a pooled value of
      0.06 (95% CI: 0.05-0.08). Being over the age of 60 years, change in bowel habit,
      weight loss, anaemia, colorectal cancer among first-degree relatives and feeling
      of incomplete evacuation of rectum appeared to increase the predictive value of
      RB. Although RB greatly increases the probability of diagnosing colorectal
      cancer, it alone may not be sufficient for proposing further sophisticated
      investigations. However, given the high specificity, subjects without RB may be
      ruled out of further investigations. Future studies should focus on strategies
      using RB as an "alarm" symptom and finding additional indications to justify
      whether there is a need for further investigations. 

PMID- 24568446
TI  - Role of hyperinsulinemia in increased risk of prostate cancer: a case control
      study from Kathmandu Valley.
AB  - AIM: To investigate the effect of hyperglycemia and hyperinsulinemia on prostate
      cancer risk. MATERIALS AND METHODS: This hospital based study was carried out
      using data retrieved from the register maintained in the Department of
      Biochemistry of a tertiary care hospital of Kathmandu, Nepal between 31st
      December, 2011 and 31st October, 2013. The variables collected were age, serum
      cholesterol, serum calcium, PSA, fasting blood glucose, serum insulin. Analysis
      was performed by descriptive statistics and testing of hypothesis using Excel
      2003, R 2.8.0, Statistical Package for the Social Sciences (SPSS) for Windows
      Version 16.0 (SPSS Inc; Chicago, IL, USA) and the EPI Info 3.5.1 Windows Version.
      RESULTS: Of the total 125 subjects enrolled in our present study, 25 cases were
      of PCa and 100 were healthy controls. The mean value of fasting plasma glucose
      was 95.5 mg/dl in cases of prostatic carcinoma and the mean value of fasting
      plasma insulin was 5.78 MUU/ml (p value: 0.0001*). The fasting insulin levels
      MUU/ml were categorized into the different ranges starting from <=2.75, >2.75 to
      <=4.10, >4.10 to <=6.10, >6.10MUU/ml. The maximum number of cases of prostatic
      carcinoma of fasting insulin levels falls in range of >6.10MUU/ml. The highest
      insulin levels (>6.10MUU/ml) were seen to be associated with an 2.55 fold risk of
      prostatic carcinoma when compared with fasting insulin levels of (<2.75 MUU/ml).
      CONCLUSIONS: Elevated fasting levels of serum insulin appear to be associated
      with a higher risk of prostate cancer.

PMID- 24568445
TI  - Joint effects of smoking and alcohol drinking on esophageal cancer mortality in
      Japanese men: findings from the Japan collaborative cohort study.
AB  - BACKGROUND: The purpose of our study was to elucidate the joint effects of
      combined smoking and alcohol intake on esophageal cancer mortality in Japanese
      men through a large cohort study with a 20-year follow-up period. MATERIALS AND
      METHODS: The Japan Collaborative Cohort Study for Evaluation of Cancer Risk (JACC
      Study) was established in the late 1980s, including 46,395 men and 64,190 women
      aged 40 years and older and younger than 80. Follow-up of these participants was
      conducted until 2009. We used the Cox proportional hazards model to analyze data
      for 42,408 people excluding female participants, 411 people with histories of
      malignant neoplasms, and 3,576 with unclear smoking and drinking data. RESULTS:
      The joint effects of age at start of smoking and amount of alcohol consumed per
      day were compared with non-smokers and non-drinkers or those consuming less than
      one unit of alcohol per day. The mortality risk was 9.33 (95% confidence
      interval, 2.55-34.2) for those who started smoking between ages 10 and 19 years
      and drinking at least three units of alcohol per day. Regarding the joint effects
      of cumulative amount of smoking and alcohol intake, the risk was high when both
      smoking and alcohol intake were above a certain level. CONCLUSIONS: In this
      Japanese cohort study, increased cancer mortality risks were observed, especially
      for people who both started smoking early and drank alcohol. Quitting smoking or
      not starting to smoke at any age and reducing alcohol consumption are important
      for preventing esophageal cancer in Japan.

PMID- 24568447
TI  - Long-term outcomes of a loop electrosurgical excision procedure for cervical
      intraepithelial neoplasia in a high incidence country.
AB  - AIM: To evaluate the operative, oncologic and obstetric outcomes of the loop
      electrosurgical excision procedure (LEEP) in cases with cervical neoplasia.
      MATERIALS AND METHODS: A retrospective cohort study was conducted on patients who
      were suspected of cervical neoplasia and therefore undergoing LEEP at Siriraj
      Hospital, Mahidol University, Thailand, during 1995-2000. Outcome measures
      included operative complications in 407 LEEP patients and long-term outcomes in
      the 248 patients with cervical intraepithelial neoplasia (CIN) who were treated
      with only LEEP. RESULTS: There were 407 patients undergoing LEEP; their mean age
      was 39.7+/-10.5 years. The histopathology of LEEP specimens revealed that 89
      patients (21.9%) had lesions <=CIN I, 295 patients (72.5%) had CIN II or III, and
      23 patients (5.6%) had invasive lesions. Operative complications were found in 15
      patients and included bleeding (n=9), and infection (n=7). After diagnostic LEEP,
      133 patients underwent hysterectomy as the definite treatment for cervical
      neoplasia. Of 248 CIN patients who had LEEP only, seven (2.8%) had suffered
      recurrence after a median of 16 (range 6-93) months; one had CIN I, one had CIN
      II, and five had CIN III. All of these recurrent patients achieved remission on
      surgical treatment with re-LEEP (n=6) or simple hysterectomy (n=1). A significant
      factor affecting recurrent disease was the LEEP margin involved with the lesion
      (p=0.05). Kaplan-Meier analysis showed 5-year and 10-year disease-free survival
      (DFS) estimates of 99.9%. Twelve patients became pregnant a total of 14 times,
      resulting in 12 term deliveries and two miscarriages - one of which was due to an
      incompetent cervix. CONCLUSIONS: LEEP for patients with cervical neoplasia
      delivers favorable surgical, oncologic and obstetric outcomes.

PMID- 24568448
TI  - beta-arrestin promotes c-Jun N-terminal kinase mediated apoptosis via a
      GABA(B)R.beta-arrestin.JNK signaling module.
AB  - Evidence is growing that the GABAB receptor, which belongs to the G protein
      coupled receptor (GPCR) superfamily, is involved in tumorigenesis. Recent studies
      have shown that beta-arrestin can serve as a scaffold to recruit signaling
      protein c-Jun N-terminal knase (JNK) to GPCR. Here we investigated whether beta
      arrestin recruits JNK to the GABAB receptor and facilitates its activation to
      affect the growth of cancer cells. Our results showed that beta-arrestin
      expression is decreased in breast cancer cells in comparison with controls. beta
      arrestin could enhance interactions of the GABABR.beta-arrestin.JNK signaling
      module in MCF-7 and T-47D cells. Further studies revealed that increased
      expression of beta-arrestin enhances the phosphorylation of JNK and induces
      cancer cells apoptosis. Collectively, these results indicate that beta-arrestin
      promotes JNK mediated apoptosis via a GABABR.beta-arrestin.JNK signaling module. 

PMID- 24568450
TI  - Potential study perspectives on mechanisms and correlations between adiposity and
      malignancy.
AB  - Adiposity is a well-recognized risk factor of type 2 diabetes and cardiovascular
      disease, and recently there is increasing evidence that excess body weight is an
      avoidable cause of cancer, including gastrointestinal, endometrial, esophageal
      adenocarcinoma, colorectal, postmenopausal breast, prostate, and renal
      malignancies. The mechanisms whereby adiposity is associated with tumor
      development remains not well understood. There are some most studied hypothesized
      mechanisms such as, high levels of insulin and free levels of insulin-like growth
      factors, sex hormones, adipocytokines, and inflammatory cytokines, adiposity
      induced hypoxia, and so on. The potential mechanisms and conclusions in adiposity
      associated with increased risk for developing malignancy, and the underlying
      cellular and molecular mechanisms will be studied very well in the near future. 

PMID- 24568449
TI  - Associations of single nucleotide polymorphisms in miR-146a, miR-196a, miR-149
      and miR-499 with colorectal cancer susceptibility.
AB  - BACKGROUND: MicroRNAs (miRNAs) are an abundant class of endogenous small non
      coding RNAs of 20-25 nucleotides in length that function as negative gene
      regulators. MiRNAs play roles in most biological processes, as well as diverse
      human diseases including cancer. Recently, many studies investigated the
      association between SNPs in miR-146a rs2910164, miR-196a2 rs11614913, miR-149
      rs229283, miR-499 rs3746444 and colorectal cancer (CRC), which results have been
      inconclusive. METHODOLOGY/PRINCIPAL FINDINGS: PubMed, EMBASE, CNKI databases were
      searched with the last search updated on November 5, 2013. For miR-196a2
      rs11614913, a significantly decreased risk of CRC development was observed under
      three genetic models (dominant model: OR = 0.848, 95%CI: 0.735-0.979, P = 0.025;
      recessive model: OR = 0.838, 95%CI: 0.721-0.974, P = 0.021; homozygous model: OR
      = 0.754, 95%CI: 0.627-0.907, P = 0.003). In the subgroup analyses, miR-196a2*T
      variant was associated with a significantly decreased susceptibility of CRC
      (allele model: OR = 0.839, 95%CI: 0.749-0.940, P = 0.000; dominant model: OR =
      0.770, 95%CI: 0.653-0.980, P = 0.002; recessive model: OR = 0.802, 95%CI: 0.685
      0.939, P = 0.006; homozygous model: OR = 0.695, 95%CI: 0.570-0.847, P = 0.000).
      As for miR-149 rs2292832, the two genetic models (recessive model: OR = 1.199,
      95% CI 1.028-1.398, P = 0.021; heterozygous model: OR = 1.226, 95% CI 1.039
      1.447, P = 0.013) demonstrated increased susceptibility to CRC. On subgroup
      analysis, significantly increased susceptibility of CRC was found in the genetic
      models (recessive model: OR = 1.180, 95% CI 1.008-1.382, P = 0.040; heterozygous
      model: OR = 1.202, 95% CI 1.013-1.425, P = 0.013) in the Asian group.
      CONCLUSIONS: These findings supported that the miR-196a2 rs11614913 and miR-149
      rs2292832 polymorphisms may contribute to susceptibility to CRC.

PMID- 24568451
TI  - Is it rational to continue anti-neoplastics with minimal toxicity even after
      progression in patients with no other options? Possibly yes.

PMID- 24568452
TI  - Predictive role of the neutrophil-to-lymphocyte ratio in patients with advanced
      hepatocellular carcinoma receiving sorafenib.

PMID- 24568453
TI  - Prevalence of common YMDD motif mutations in long term treated chronic HBV
      infections in a Turkish population.

PMID- 24568454
TI  - An update on occupation and prostate cancer.
AB  - BACKGROUND: Our aim was to identify gaps and limitations in the current
      literature and to make recommendations for future research required to address
      these. MATERIALS AND METHODS: We reviewed occupational exposures and related
      factors associated with the risk of prostate cancer between 2000 and 2012. These
      included chemical, ergonomic, physical or environmental, and psychosocial factors
      which have been reported by epidemiological studies across a range of industries.
      RESULTS: The results are inconsistent from study to study and generally this is
      due to the reliance upon the retrospectivity of case-control studies and
      prevalence (ecological) studies. Exposure assessment bias is a recurring
      limitation of many of the studies in this review. CONCLUSIONS: We consider there
      is insufficient evidence to implicate prostate cancer risk for ergonomic,
      physical, environmental or psychosocial factors, but there is sufficient evidence
      to implicate toxic metals, polychlorinated biphenyls (PCBs) and polycyclic
      aromatic hydrocarbons (PAHs). More research is required to identify specific
      pesticides that may be associated with risk of prostate cancer.

PMID- 24568455
TI  - PLGA-based nanoparticles as cancer drug delivery systems.
AB  - Poly (lactic-co-glycolic acid) (PLGA) is one of the most effective biodegradable
      polymeric nanoparticles (NPs). It has been approved by the US FDA to use in drug
      delivery systems due to controlled and sustained- release properties, low
      toxicity, and biocompatibility with tissue and cells. In the present review, the
      structure and properties of PLGA copolymers synthesized by ring-opening
      polymerization of DL-lactide and glicolide were characterized using 1H nuclear
      magnetic resonance spectroscopy, gel permeation chromatography, Fourier transform
      infrared spectroscopy and differential scanning calorimetry. Methods of
      preparation and characterization, various surface modifications, encapsulation of
      diverse anticancer drugs, active or passive tumor targeting and different release
      mechanisms of PLGA nanoparticles are discussed. Increasing experience in the
      application of PLGA nanoparticles has provided a promising future for use of
      these nanoparticles in cancer treatment, with high efficacy and few side effects.

PMID- 24568456
TI  - Head and neck cancer: global burden and regional trends in India.
AB  - The actual burden of head and neck cancer in India is much greater than reflected
      through the existing literature and hence can be regarded as a 'tip of iceberg'
      situation. This has further been evident by the recent reports of 'Net-based
      Atlas of Cancer in India'. South-east Asia is likely to face sharp increases of
      over 75% in the number of cancer deaths in 2020 as compared to 2000. Since the
      percentage increase of Indian population has been nearly twice that of the world
      in last 15 years there is a likelihood of increase in cancer burden with the same
      proportion. The distribution of population based cancer registries is grossly
      uneven with certain important parts of the country being not represented at all
      and hence the current cancer burden is not reflected by registry data. However,
      the pathetic situation of health care system in major parts of the country as
      also emphasized by the World Bank, is not suitable to provide anywhere near
      accurate data on cancer burden. Head and neck cancer (including thyroid lesions)
      is third most common malignancy seen in both the sexes across the globe but is
      the commonest malignancy encountered in Indian males. Also oral cavity cancer is
      the most prevalent type amongst the males and one of the highest across the
      globe. This article reviews the latest global and national situation with an
      especial emphasis on head and neck cancer. Furthermore this review focuses on
      burden in different sub sites at national and global levels. 

PMID- 24568457
TI  - Signal transducer and activator of transcription 3 - a promising target in
      colitis-associated cancer.
AB  - Colorectal cancer (CRC) is the third most common malignancy and fourth most
      common cause of cancer mortality worldwide. Untreated chronic inflammation in the
      intestine ranks among the top three high-risk conditions for colitis-associated
      colorectal cancer (CAC). Signal Transducer and Activator of Transcription 3
      (STAT3) protein is a member of the STAT family of transcription factors often
      deregulated in CRC. In this review, we try to emphasize the critical role of
      STAT3 in CAC as well as the crosstalk of STAT3 with inflammatory cytokines,
      nuclear factor (NF)- kappaB, PI3K/Akt, Mammalian Target of Rapamycin (mTOR),
      Notch, Wnt/beta-catenin and microRNA (MiR) pathways. STAT3 is considered as a
      primary drug target to treat CAC in humans and rodents. Also we updated the
      findings for inhibitors of STAT3 with regard to effeects on tumorigenesis. This
      review will hopefully provide insights on the use of STAT3 as a therapeutic
      target in CAC. 

PMID- 24568458
TI  - Oxidative stress and skin diseases: possible role of physical activity.
AB  - BACKGROUND: The skin is the largest body organ that regulates excretion of
      metabolic waste products, temperature, and plays an important role in body
      protection against environmental physical and chemical, as well as biological
      factors. These include agents that may act as oxidants or catalysts of reactions
      producing reactive oxygen species (ROS), reactive nitrogen species (RNS), and
      other oxidants in skin cells. An increased amount of the oxidants, exceeding the
      antioxidant defense system capacity is called oxidative stress, leading to
      chronic inflammation, which, in turn, can cause collagen fragmentation and
      disorganization of collagen fibers and skin cell functions, and thus contribute
      to skin diseases including cancer. Moreover, research suggests that oxidative
      stress participates in all stages of carcinogenesis. We report here a summary of
      the present state of knowledge on the role of oxidative stress in pathogenesis of
      dermatologic diseases, defensive systems against ROS/RNS, and discuss how
      physical activity may modulate skin diseases through effects on oxidative stress.
      The data show duality of physical activity actions: regular moderate activity
      protects against ROS/RNS damage, and endurance exercise with a lack of training
      mediates oxidative stress. These findings indicate that the redox balance should
      be considered in the development of new antioxidant strategies linked to the
      prevention and therapy of skin diseases.

PMID- 24568459
TI  - Breast magnetic resonance imaging indications in current practice.
AB  - Although mammography is the primary imaging modality for the breast, it has its
      limitations especially with dense breast parenchyma. Breast magnetic resonance
      imaging (MRI) has evolved into an important adjunctive tool as it is currently
      the most sensitive technique for breast cancer detection. Despite this high
      sensitivity, overlap in the appearances of some benign and malignant breast
      lesions results in additional unnecessary intervention with negative results.
      These false positives, in addition to high cost and limited availability,
      necessitate establishing proper indications for breast MRI. The literature was
      here reviewed for recent clinical trials, meta-analyses and review papers which
      have studied this important subject. PubMed; the US national library of medicine,
      was utilized to review the literature in the last twenty years. Using the
      obtained information, current uses of breast MRI are discussed in this paper to
      determine the indications which are relevant to clinical practice. 

PMID- 24568460
TI  - Insights into the diverse roles of miR-205 in human cancers.
AB  - The recent discovery of tiny microRNAs (miRNAs) has brought about awareness of a
      new class of regulators of diverse pathways in many physiological and
      pathological processes, such as tumorigenesis. They modulate gene expression by
      targeting plethora of mRNAs, mostly reducing the protein yield of a targeted
      mRNA. With accumulation of information on characteristics of miR-205, complex and
      in some cases converse roles of miR-205 in tumor initiation, progression and
      metastasis are emerging. miR-205 acts either as an oncogene via facilitating
      tumor initiation and proliferation, or in some cases as a tumor suppressor
      through inhibiting proliferation and invasion. The aim of this review is to
      discuss miR-205 roles in different types of cancers. Given the critical effects
      of deregulated miR-205 on processes involved in tumorigenesis, they hold
      potential as novel therapeutic targets and biomarkers. 

PMID- 24568461
TI  - Preventive and therapeutic roles of ginseng - focus on colon cancer.
AB  - Colorectal cancer is one of the most prevalent diseases all over the world. Early
      screening and start of chemotherapy is effective in decreasing mortality. This
      type of cancer can be controlled to some extent via a healthy diet rich in fruit
      and vegetables. Ginseng is a plant which has been consumed as a herbal medicine
      for thousands of years in Asian countries. Several in vitro and in vivo studies
      have shown that this plant not only reduces the incidence of colorectal cancer,
      but also improves patient's status by enhancing the effects of chemotherapy
      drugs. However, further studies are needed to prove this relationship. We briefly
      review ginseng and its components such as ginsenosides reported anticancer
      effects and their mechanisms of action. Understanding these relationships may
      produce insights into chemical and pharmacological approaches for enhancing the
      chemo preventive effects of ginsenosides and for developing novel anticancer
      agents. 

PMID- 24568462
TI  - Barriers to cancer screening among medical aid program recipients in the Republic
      of Korea: a qualitative study.
AB  - Few studies have examined reasons why those with low socioeconomic status do not
      adequately receive cancer screening. We therefore conducted a qualitative study
      to assess the barriers to cancer screening in people with low socioeconomic
      status, and to examine the reasons why Medical Aid Program (MAP) recipients do
      not participate in the National Cancer Screening Program (NCSP). A focus group
      methodology was used. Participants included MAP recipients (men aged 45-79 years,
      women aged 35-79 years) who had been invited to cancer screening at least twice
      based on the NCSP protocol, but had not been screened for any cancer from 2009
      2012. We recruited participants living in the cities of Goyang and Paju. A total
      of 23 MAP recipients participated in four focus group discussions, including 12
      men and 11 women. In this qualitative study, we identified six barriers to
      screening: lack of trust in the NCSP and cancer screening units; fear of being
      diagnosed with cancer; discomfort or pain from the screening procedure; lack of
      time, lack of knowledge about cancer screening or lack of awareness of the
      existence of the NCSP; physical disability or underlying disease; and logistic
      barriers. Interventions such as individualized counseling, letters and reminders,
      or other individually-targeted strategies, especially for those with lower
      socioeconomic status are required to increase participation and reduce
      disparities in cancer screening. 

PMID- 24568463
TI  - Expression of nuclear factor kappa B (NF-kappaB) as a predictor of poor
      pathologic response to chemotherapy in patients with locally advanced breast
      cancer.
AB  - BACKGROUND: NF-kappaB inhibits apoptosis through induction of antiapoptotic
      proteins and suppression of proapoptotic genes. Various chemotherapy agents
      induce NF-kappaB translocation and target gene activation. We conducted the
      present study to assess the predictive value of NF-kappaB regarding pathologic
      responses after receiving neoadjuvant chemotherapy. MATERIALS AND METHODS: We
      enrolled 131 patients with locally advanced invasive ductal breast carcinoma.
      Immunohistochemistry (IHC) was used to detect NF-kappaB expression. Evaluation of
      pathologic response was elaborated with the Ribero classification. RESULTS:
      Expression of NF-kappaB was significantly associated with poor pathological
      response (p=0.02). From the multivariate analysis, it was found that the positive
      expression of NF-kappaB yielded RR=1.74 (95%CI 0.77 to 3.94). CONCLUSIONS: NF
      kappaB can be used as a predictor of poor pathological response after neoadjuvant
      chemotherapy.

PMID- 24568464
TI  - Pattern of reproductive cancers in India.
AB  - BACKGROUND: Reproductive cancers are those that affect the human organs that are
      involved in producing offspring. An attempt is made in the present communication
      to assess the magnitude and pattern of reproductive cancers, including their
      treatment modalities, in India. The cancer incidence data related to reproductive
      cancers collected by five population-based urban registries, namely Bangalore,
      Bhopal, Chennai, Delhi and Mumbai, for the years 2006-08 were utilized. The
      reproductive cancers among females constituted around 25% of the total and around
      9% among males. Among females, the three major contributors were cervix (55.5%),
      ovary (26.1%) and corpus uteri (12.4%). Similarly among males, the three major
      contributors were prostate (77.6%), penis (11.6%) and testis (10.5%). For
      females, the AAR of reproductive cancers varied between 30.5 in the registry of
      Mumbai to 37.3 in the registry of Delhi. In males, it ranged between 6.5 in the
      registry of Bhopal to 14.7 in the registry of Delhi. For both males and females,
      the individual reproductive cancer sites showed increasing trends with age. The
      leading treatment provided was: radio-therapy in combination with chemo-therapy
      for cancers of cervix (48.3%) and vagina (43.9%); surgery in combination with
      chemo-therapy (54.9%) for ovarian cancer; and surgery in combination with radio
      therapy for the cancers of the corpus uteri (39.8%). In males, the leading
      treatment provided was hormone-therapy for prostate cancer (39.6%), surgery for
      penile cancer (81.3%) and surgery in combination with chemo-therapy for cancer of
      the testis (57.6%).

PMID- 24568466
TI  - Antitumor activity of lentivirus-mediated interleukin -12 gene modified dendritic
      cells in human lung cancer in vitro.
AB  - OBJECTIVES: Dendritic cell (DC)-based tumor immunotherapy needs an immunogenic
      tumor associated antigen (TAA) and an effective approach for its presentation to
      lymphocytes. In this study we explored whether transduction of DCs with
      lentiviruses (LVs) expressing the human interleukin-12 gene could stimulate
      antigen- specific cytotoxic T cells (CTLs) against human lung cancer cells in
      vitro. METHODS: Peripheral blood monocyte- derived DCs were transduced with a
      lentiviral vector encoding human IL-12 gene (LV-12). The anticipated target of
      the human IL-12 gene was detected by RT-PCR. The concentration of IL-12 in the
      culture supernatant of DCs was measured by ELISA.Transduction efficiencies and
      CD83 phenotypes of DCs were assessed by flow cytometry. DCs were pulsed with
      tumor antigen of lung cancer cells (DC+Ag) and transduced with LV-12 (DC-LV
      12+Ag). Stimulation of T lymphocyte proliferation by DCs and activation of
      cytotoxic T-lymphocytes (CTL) stimulated by LV-12 transduced DCs pulsed with
      tumor antigen against A549 lung cancer cells were assessed with methyl
      thiazolyltetrazolium (MTT). RESULTS: A recombinant lentivirus expressing the IL
      12 gene was successfully constructed. DC transduced with LV-12 produced higher
      levels of IL-12 and expressed higher levels of CD83 than non-transduced. The DC
      modified by interleukin -12 gene and pulsed with tumor antigen demonstrated good
      stimulation of lymphocyte proliferation, induction of antigen-specific cytotoxic
      T lymphocytes and anti- tumor effects. CONCLUSIONS: Dendritic cells transduced
      with a lentivirus-mediated interleukin-12 gene have an enhanced ability to kill
      lung cancer cells through promoting T lymphocyte proliferation and cytotoxicity.

PMID- 24568465
TI  - Transient knock down of Grp78 reveals roles in serum ferritin mediated pro
      inflammatory cytokine secretion in rat primary activated hepatic stellate cells.
AB  - Chronic liver diseases, including cancer, are characterized by inflammation and
      elevated serum ferritin (SF). However, the causal-relationship remains unclear.
      This study used primary rat hepatic stellate cells (HSC) as a model to
      investigate effects of physiological SF concentrations (10, 100 and 1000 pM)
      because HSCs play a central role in the development and progression of liver
      fibrosis. Physiological concentrations of SF, either horse SF or human serum,
      induced pro-inflammatory cytokine IL1beta, IL6 and TNFalpha secretion in rat
      activated HSCs (all p<0.05). By contrast, treatment did not alter activation
      marker alphaSMA expression. The presence of SF markedly enhanced expression of
      Grp78 mRNA (p<0.01). Furthermore, transient knock down of Grp78 by endotoxin EGF-
      SubA abolished SF-induced IL1beta and TNFalpha secretion in activated HSCs (all
      p<0.05). In conclusion, our results showed that at physiological concentrations
      SF functions as a pro-inflammatory mediator in primary rat HSCs. We also provide
      a molecular basis for the action of SF and identified Grp78-associated ER stress
      pathways as a novel potential therapeutic target for resolution of fibrosis and
      possible prevention of liver cancer. 

PMID- 24568468
TI  - Gender and social disparities in esophagus cancer incidence in Iran, 2003-2009: a
      time trend province-level study.
AB  - BACKGROUND: Esophagus cancer (EC) is among the five most common cancers in both
      sexes in Iran, with an incidence rate well above world average. Social rank (SR)
      of individuals and regions are well-known independent predictors of EC incidence.
      The aim of current study was to assess gender and social disparities in EC
      incidence across Iran's provinces through 2003-2009. MATERIALS AND METHODS: Data
      on distribution of population at province level were obtained from the
      Statistical Centre of Iran. Age-standardized incidence rates of EC were gathered
      from the National Cancer Registry. The Human Development Index (HDI) was used to
      assess the province social rank. Rate ratios and Kunst and Mackenbach relative
      indices of inequality (RIIKM) were used to assess gender and social inequalities,
      respectively. Annual percentage change (APC) was calculated using joinpoint
      regression. RESULTS: EC incidence rate increased 4.6% and 6.5% per year among
      females and males, respectively. There were no gender disparities in EC incidence
      over the study period. There were substantial social disparities in favor of
      better-off provinces in Iran. These social disparities were generally the same
      between males and females and were stable over the study period. CONCLUSIONS: The
      results showed an inverse association between the provinces' social rank and EC
      incidence rate in Iran. In addition, I found that, in contrast with international
      trends, women are at the same risk of EC as men in Iran. Further investigations
      are needed to explain these disparities in EC incidence across the provinces.

PMID- 24568467
TI  - Apoptosis-inducing activity of HPLC fraction from Voacanga globosa (Blanco) Merr.
      on the human colon carcinoma cell.
AB  - Voacanga globosa (Blanco), a plant endemic to the Philippines, is traditionally
      used especially by indigenous people of Bataan in the treatment of ulcers, wounds
      and tumorous growths. This study aimed to provide scientific evidence to
      therapeutic properties by determining cytotoxic and pro-apoptotic activity of
      HPLC fractions from leaves on HCT116 human colon carcinoma and A549 human lung
      carcinoma cell lines. Ethanolic extraction was performed on V globosa leaves
      followed by hexane and ethyl acetate partitioning. Silica gel column
      chromatography and high performance liquid chromatography (HPLC) produced MP1,
      MP2 and MP3 fractions. Cytotoxic activity of the fractions was determined through
      MTT assay against the cancer cell lines HCT116 and A549 and the non-cancer AA8
      Chinese hamster ovarian cell line. Pro-apoptotic activities of the most active
      fractions were further assessed through DAPI staining, TUNEL assay and JC-1
      mitochondrial membrane potential assay with HCT116 cells. While the MP1 fraction
      exerted no significant activity against all cell lines tested, MP2 and MP3
      fractions demonstrated high toxicity against HCT116 and A549 cells. The MP3
      fraction induced formation of apoptotic bodies, condensed DNA and other
      morphological changes consistent with apoptosis of HCT116 cells and TUNEL assay
      showed significant increase in DNA fragmentation over time. In these cells, the
      MP3 fraction also induced mitochondrial membrane destabilization, which is
      generally associated with the beginning of apoptosis. Phytochemical analysis
      demonstrated the presence only of saponins and terpenoids in the MP3 fraction.
      The results indicate that the MP3 fraction exerts cytotoxic activity on HCT116
      cells via induction of apoptosis triggered by loss of mitochondrial membrane
      potential crucial for cell survival. 

PMID- 24568469
TI  - Down-regulation of Mcl-1 by small interference RNA induces apoptosis and
      sensitizes HL-60 leukemia cells to etoposide.
AB  - BACKGROUND: Acute myeloid leukemia (AML) is a fatal hematological malignancy
      which is resistant to a variety of chemotherapy drugs. Myeloid cell leukemia-1
      (Mcl-1), a death-inhibiting protein that regulates apoptosis, has been shown to
      be overexpressed in numerous malignancies. In addition, it has been demonstrated
      that the expression level of the Mcl-1 gene increases at the time of leukemic
      relapse following chemotherapy. The aim of this study was to target Mcl-1 by
      small interference RNA (siRNA) and analyze its effects on survival and
      chemosensitivity of acute myeloid leukemia cell line HL-60. MATERIALS AND
      METHODS: siRNA transfection was performed with a liposome approach. The
      expression levels of mRNA and protein were measured by real-time quantitative PCR
      and Western blot analysis, respectively. Trypan blue assays were performed to
      evaluate tumor cell growth after siRNA transfection. The cytotoxic effects of Mcl
      1 siRNA (siMcl-1) and etoposide were determined using MTT assay on their own and
      in combination. Apoptosis was quantified using a DNA-histone ELISA assay.
      RESULTS: Transfection with siMcl-1 significantly suppressed the expression of Mcl
      1 mRNA and protein in a time- dependent manner, resulting in strong growth
      inhibition and spontaneous apoptosis. Surprisingly, pretreatment with siMcl-1
      synergistically enhanced the cytotoxic effect of etoposide. Furthermore, Mcl-1
      down-regulation significantly increased apoptosis sensitivity to etoposide. No
      significant biological effects were observed with negative control siRNA
      treatment. CONCLUSIONS: Our results suggest that specific suppression of Mcl-1 by
      siRNA can effectively induce apoptosis and overcome chemoresistance of leukemic
      cells. Therefore, siMcl-1 may be a potent adjuvant in leukemia chemotherapy.

PMID- 24568470
TI  - Impact of chronic hepatitis B and hepatitis C on adverse hepatic fibrosis in
      hepatocellular carcinoma related to betel quid chewing.
AB  - The pathogenesis of hepatocellular carcinoma (HCC) related to habitual betel quid
      (BQ) chewing is unclear. Risk of HCCis increased with adverse hepatic fibrosis.
      This study aimed to assess the impact of chronic viral hepatitis on adverse
      hepatic fibrosis in HCC related to BQ chewing. This hospital-based case-control
      study enrolled 200 pairs of age- and gender-matched patients with HCC and
      unrelated healthy controls. Serologic hepatitis B surface antigen (HBsAg),
      antibodies to hepatitis C virus (anti-HCV), alpha-fetoprotein (AFP), and
      surrogate markers for significant hepatic fibrosis were measured. Information on
      substance-use habits was obtained with a questionnaire. By analysis of surrogate
      markers for hepatic fibrosis, the prevalence of significant hepatic fibrosis in
      patients chewing BQ was between 45.8% and 91.7%, whereas that for patients
      without BQ chewing was between 18.4% and 57.9%. The difference was significant (P
      <0.05 for each surrogate marker). Multivariate analysis indicated that cirrhosis
      with Child-Pugh C (odds ratio (OR) = 3.28; 95% confidence interval (CI), 1.29-
      8.37), thrombocytopenia (OR = 3.92, 95% CI, 1.77-8.68), AFP >400 mg/L (OR = 2.21,
      95% CI, 1.05-4.66) and male gender (OR = 4.06, 95% CI, 1.29-12.77) were
      independent factors associated with habitual BQ chewing. In conclusion, adverse
      hepatic fibrosis and severe liver damage play important roles in the pathogenesis
      of BQ- related HCC, which could be aggravated by chronic hepatitis B and
      hepatitis C. BQ-cessation programs and prevention of chronic HBV/HCV infection
      are needed to prevent HCC related to BQ chewing. 

PMID- 24568471
TI  - Effects of tissue factor, PAR-2 and MMP-9 expression on human breast cancer cell
      line MCF-7 invasion.
AB  - OBJECTIVE: This study aimed to explore the expression of tissue factor (TF),
      protease activated receptor-2 (PAR-2), and matrix metalloproteinase-9 (MMP-9) in
      the MCF-7 breast cancer cell line and influence on invasiveness. METHODS: Stable
      MCF-7 cells transfected with TF cDNA and with TF ShRNA were established. TF, PAR
      2, and MMP-9 protein expression was analyzed using indirect immunofluorescence
      and invasiveness was evaluated using a cell invasion test. Effects of an
      exogenous PAR-2 agonist were also examined. RESULTS: TF protein expression
      significantly differed between the TF cDNA and TF ShRNA groups. MMP-9 protein
      expression was significantly correlated with TF protein expression, but PAR-2
      protein expression was unaffected. The PAR- 2 agonist significantly enhanced MMP
      9 expression and slightly increased TF and PAR-2 expression in the TF ShRNA
      group, but did not significantly affect protein expression in MCF-7 cells
      transfected with TF cDNA. TF and MMP-9 expression was positively correlated with
      the invasiveness of tumor cells. CONCLUSION: TF, PAR-2, and MMP-9 affect
      invasiveness of MCF-7 cells. TF may increase MMP-9 expression by activating PAR
      2.

PMID- 24568472
TI  - Application of lobaplatin in trans-catheter arterial chemoembolization for
      primary hepatic carcinoma.
AB  - OBJECTIVE: To explore the efficiency of single application of lobaplatin in tran
      scatheter arterial chemoembolization (TACE) for patients with a primary hepatic
      carcinoma who were unable or unwilling to undergo surgery. METHODS: 173 patients
      with primary hepatic carcinoma diagnosed by imaging or pathology were randomly
      divided into experimental and control groups and respectively treated with
      lobaplatin and pirarubicin hydrochloride as chemotherapeutic drugs for TACE. The
      amount of iodipin was regulated according to the tumor number and size, and then
      gelatin sponge or polyvinyl alcohol particles were applied for embolisms. The
      efficiency of treatment in the two groups was compared with reference to survival
      time and therapeutic response. RESULTS: The experimental group (single lobaplatin
      as chemotherapy drug) was superior to control group (single pirarubicin
      hydrochloride as chemotherapy drug) in the aspects of survival time and
      therapeutic response, with statistical significance. CONCLUSIONS: Single
      lobaplatin can be as a chemotherapy drug in TACE and has better efficiency in the
      aspects of mean survival time and therapeutic response, deserving to be
      popularized in the clinic.

PMID- 24568473
TI  - Distribution of HPV genotypes in cervical cancer in multi- ethnic Malaysia.
AB  - BACKGROUND: Cervical cancer is the third commonest type of cancer among women in
      Malaysia. Our aim was to determine the distribution of human papilloma virus
      (HPV) genotypes in cervical cancer in our multi-ethnic population. MATERIALS AND
      METHODS: This was a multicentre study with a total of 280 cases of cervical
      cancer from 4 referral centres in Malaysia, studied using real-time polymerase
      chain reaction (qPCR) detection of 12 high risk-HPV genotypes. RESULTS: Overall
      HPV was detected in 92.5% of cases, in 95.9% of squamous cell carcinomas and
      84.3%of adenocarcinomas. The five most prevalent high-risk HPV genotypes were HPV
      16 (68.2%), 18 (40%), 58 (10.7%), 33 (10.4%) and 52 (10.4%). Multiple HPV
      infections were more prevalent (55.7%) than single HPV infections (36.8%). The
      percentage of HPV positive cases in Chinese, Malays and Indians were 95.5%, 91.9%
      and 80.0%, respectively. HPV 16 and 18 genotypes were the commonest in all ethnic
      groups. We found that the percentage of HPV 16 infection was significantly higher
      in Chinese (75.9%) compared to Malays (63.7%) and Indians (52.0%) (p<0.05), while
      HPV 18 was significantly higher in Malays (52.6%) compared to Chinese (25.0%) and
      Indians (28%) (p<0.05). Meanwhile, HPV 33 (17.9%) and 52 (15.2%) were also more
      commonly detected in the Chinese (p<0.05). CONCLUSIONS: This study showed that
      the distribution of HPV genotype in Malaysia is similar to other Asian countries.
      Importantly, we found that different ethnic groups in Malaysia have different HPV
      genotype infection rates, which is a point to consider during the implementation
      of HPV vaccination.

PMID- 24568474
TI  - Relationships between EGFR mutation status of lung cancer and preoperative
      factors - are they predictive?
AB  - BACKGROUND: The epidermal growth factor receptor (EGFR) mutation status of lung
      cancer is important because it means that EGFR-tyrosine kinase inhibitor
      treatment is indicated. The purpose of this prospective study is to determine
      whether EGFR mutation status could be identified with reference to preoperative
      factors. MATERIALS AND METHODS: One hundred-forty eight patients with lung cancer
      (111 adenocarcinomas, 25 squamous cell carcinomas and 12 other cell types) were
      enrolled in this study. The EGFR mutation status of each lung cancer was analyzed
      postoperatively. RESULTS: There were 58 patients with mutant EGFR lung cancers
      (mutant LC) and 90 patients with wild-type EGFR lung cancers (wild-type LC).
      There were significant differences in gender, smoking status, maximum tumor
      diameter in chest CT, type of tumor shadow, clinical stage between mutant LC and
      wild-type LC. EGFR mutations were detected only in adenocarcinomas. Maximum
      standardized uptake value (SUVmax:3.66+/-4.53) in positron emission tomography
      computed tomography of mutant LC was significantly lower than that (8.26+/-6.11)
      of wild-type LC (p<0.0001). Concerning type of tumor shadow, the percentage of
      mutant LC was 85.7% (6/7) in lung cancers with pure ground glass opacity (GGO),
      65.3%(32/49) in lung cancers with mixed GGO and 21.7%(20/92) in lung cancers with
      solid shadow (p<0.0001). For the results of discriminant analysis, type of tumor
      shadow (p=0.00036) was most significantly associated with mutant EGFR. Tumor
      histology (p=0.0028), smoking status (p=0.0051) and maximum diameter of tumor
      shadow in chest CT (p=0.047) were also significantly associated with mutant EGFR.
      The accuracy for evaluating EGFR mutation status by discriminant analysis was
      77.0% (114/148). CONCLUSIONS: Mutant EGFR is significantly associated with lung
      cancer with pure or mixed GGO, adenocarcinoma, never-smoker, smaller tumor
      diameter in chest CT. Preoperatively, EGFR mutation status can be identified
      correctly in about 77 % of lung cancers.

PMID- 24568475
TI  - Bayesian method for modeling male breast cancer survival data.
AB  - BACKGROUND: With recent progress in health science administration, a huge amount
      of data has been collected from thousands of subjects. Statistical and
      computational techniques are very necessary to understand such data and to make
      valid scientific conclusions. The purpose of this paper was to develop a
      statistical probability model and to predict future survival times for male
      breast cancer patients who were diagnosed in the USA during 1973-2009. MATERIALS
      AND METHODS: A random sample of 500 male patients was selected from the
      Surveillance Epidemiology and End Results (SEER) database. The survival times for
      the male patients were used to derive the statistical probability model. To
      measure the goodness of fit tests, the model building criterions: Akaike
      Information Criteria (AIC), Bayesian Information Criteria (BIC), and Deviance
      Information Criteria (DIC) were employed. A novel Bayesian method was used to
      derive the posterior density function for the parameters and the predictive
      inference for future survival times from the exponentiated Weibull model,
      assuming that the observed breast cancer survival data follow such type of model.
      The Markov chain Monte Carlo method was used to determine the inference for the
      parameters. RESULTS: The summary results of certain demographic and socio
      economic variables are reported. It was found that the exponentiated Weibull
      model fits the male survival data. Statistical inferences of the posterior
      parameters are presented. Mean predictive survival times, 95% predictive
      intervals, predictive skewness and kurtosis were obtained. CONCLUSIONS: The
      findings will hopefully be useful in treatment planning, healthcare resource
      allocation, and may motivate future research on breast cancer related survival
      issues.

PMID- 24568476
TI  - Cervical cancer screening and analysis of potential risk factors in 43,567 women
      in Zhongshan, China.
AB  - OBJECTIVE: The objective of this study was to establish a program model for use
      in wide-spread cervical cancer screening. METHODS: Cervical cancer screening was
      conducted in Zhongshan city in Guangdong province, China through a coordinated
      network of multiple institutes and hospitals. A total of 43,567 women, 35 to 59
      years of age, were screened during regular gynecological examinations using the
      liquid-based ThinPrep cytology test (TCT). Patients who tested positive were
      recalled for further treatment. RESULTS: The TCT-positive rate was 3.17%, and
      63.4% of these patients returned for follow-up. Pathology results were positive
      for 30.5% of the recalled women. Women who were younger than 50 years of age,
      urban dwelling, low-income, had a history of cervical disease, began having sex
      before 20 years of age, or had sex during menstruation, were at elevated risk for
      a positive TCT test. The recall rate was lower in women older than 50 years of
      age, urban dwelling, poorly educated, and who began having sex early. A higher
      recall rate was found in women 35 years of age and younger, urban dwelling, women
      who first had sex after 24 years of age, and women who had sex during
      menstruation. The positive pathology rate was higher in urban women 50 years of
      age and younger and women who tested positive for human papillomavirus.
      CONCLUSION: An effective model for large-scale cervical cancer screening was
      successfully established. These results suggest that improvements are needed in
      basic education regarding cervical cancer screening for young and poorly educated
      women. Improved outreach for follow-up is also necessary to effectively control
      cervical cancer.

PMID- 24568477
TI  - Resveratrol inhibits oesophageal adenocarcinoma cell proliferation via AMP
      activated protein kinase signaling.
AB  - Resveratrol has been examined in several model systems for potential effects
      against cancer. Adenosine monophosphate-activated protein kinase (AMPK) is
      reported to suppress proliferation in most eukaryocyte cells. Whether resveratrol
      via AMPK inhibits proliferation of oesophageal adenocarcinoma cells (OAC) is
      unknown. The aim of this study was to determine the roles of AMPK in the
      protective effects of resveratrol in OAC proliferation and to elucidate the
      underlying mechanisms. Treatment of cultured OAC derived from human subjects or
      cell lines with resveratrol resulted in decreased cell proliferation. Further,
      inhibition of AMPK by pharmacological reagent or genetical approach abolished
      resveratrol-suppressed OAC proliferation, reduced the level of p27Kip1, a cyclin
      dependent kinase inhibitor, and increased the levels of S-phase kinase-associated
      protein 2 (Skp2) of p27Kip1-E3 ubiquitin ligase and 26S proteasome activity
      reduced by resveratrol. Furthermore, gene silencing of p27Kip1 reversed
      resveratrol-suppressed OAC proliferation. In conclusion, these findings indicate
      that resveratrol inhibits Skp2-mediated ubiquitylation and 26S proteasome
      dependent degradation of p27Kip1 via AMPK activation to suppress OAC
      proliferation.

PMID- 24568479
TI  - Single center experience on causes of cancer patients visiting the emergency
      department in southwest Turkey.
AB  - BACKGROUND: Emergency departments are visited by cancer patients for palliation
      of cancer-related symptoms, management of treatment-related side effects,
      oncologic emergencies, co-morbidities, and/or end of life care. In this study, we
      aimed to identify the characteristics of cancer patients admitted to an emergency
      medicine department in Southwest Turkey. MATERIALS AND METHODS: In this
      retrospective descriptive study, a total of 304 emergency department admissions
      of 102 patients with cancer due to medical conditions were evaluated. Descriptive
      statistical methods, statistical analysis for correlation, Student's t-test, chi
      square tests and logistic regression test were used. RESULTS: The majority of
      patients visiting to emergency departments were male (n=66, 65%) and over 65
      years of age (53, 52%). Some 30% (n=31) had a lung cancer diagnosis, 32% (n=33)
      presentation with dyspnea, 53% (n=55) with metastasis, 30% (n=16) with multiple
      metastatic lesions in lung, and 68% (n=70) had a poor ECOG performance status
      (score 3 to 4). CONCLUSIONS: Emergency departments have valuable roles in
      managing and caring for patients with malignancies.

PMID- 24568478
TI  - Clinical value of dual-phase 18F-FDG SPECT with serum procalcitonin for
      identification of etiology in tumor patients with fever of unknown origin.
AB  - OBJECTIVE: The purpose of the study was to evaluate clinical value of dual-phase
      18F-FDG SPECT with serum procalcitonin (PCT) in identifying cancers in patients
      with fever of unknown origin (FUO). METHODS: PCT test and dual-phase 18F-FDG
      SPECT were sequentially performed on 50 consecutive patients with FUO. Two
      radiologists evaluated all 18F-FDG SPECT data independently. A consensus was
      reached if any difference of opinions existed. Final diagnosis was based on a
      comprehensive analysis of results for the PCT test, dual- phase 18F-FDG SPECT and
      bacterial cultivation, regarded as a gold standard. RESULTS: Among 50 patients,
      34 demonstrated PCT >= 0.5 MUg/L. Coincidence imaging showed in 37 patients with
      inflammatory lesions, and 13 with malignancy. Finally, 36 bacterial, 1 fungal and
      1 viral infections, as well as 12 cancerous fevers were confirmed by dual-phase
      18F-FDG SPECT with PCT, combined with bacterial cultivation and clinical follow
      up. CONCLUSION: Our study demonstrated that dual-phase 18F-FDG SPECT in
      association with PCT could be a valuable tool for diagnosis in tumor patients
      with FUO.

PMID- 24568480
TI  - Impact of tumor length on survival for patients with resected esophageal cancer.
AB  - BACKGROUND: Tumor length in patients with esophageal cancer (EC) has recently
      received great attention. However, its prognostic role for EC is controversial.
      The purpose of our study was to characterize the prognostic value of tumor length
      in EC patients and offer the optimum cut-off point of tumor length by reliable
      statistical methods. MATERIALS AND METHODS: A retrospective analysis was
      conducted on 71 consecutive patients with EC who underwent surgery. ROC curve
      analysis was used to determine the optimal cut-off point for tumor length,
      measured with a handheld ruler after formalin fixation. Correlations between
      tumor length and other factors were surveyed, and overall survival (OS) rates
      were compared between the two groups. Potential prognostic factors were evaluated
      by univariate Kaplan-Meier survival analysis. A P value less than 0.05 was
      considered significant. RESULTS: There were a total of 71 patients, with a male/
      female divide of 43/28 and a median age of 59. Characteristics were as follows:
      squamous/adenocarcinoma, 65/6; median tumor length, 4 (0.9-10); cut-off point for
      tumor length, 4cm. Univariate analysis prognostic factors were tumor length and
      modality of therapy. One, three and five year OS rates were 84, 43 and 43% for
      tumors with <=4cm length, whereas the rates were 75, 9 and 0% for tumors >4 cm.
      There was a significant association between tumor length and age, sex, weight
      loss, tumor site, histology, T and N scores, differentiation, stage, modality of
      therapy and longitudinal margin involvement. CONCLUSIONS: Future studies for
      modification of the EC staging system might consider tumor length too as it is an
      important prognostic factor. Further assessment with larger prospective datasets
      and practical methods (such as endoscopy) is needed to establish an optimal cut
      off point for tumor length.

PMID- 24568481
TI  - Observational study on patient's satisfactions and quality of life (QoL) among
      cancer patients receiving treatment with palliative care intent in a tertiary
      hospital in Malaysia.
AB  - The main objective of palliative treatment for cancer patients has been to
      maintain, if not improve, the quality of life (QoL). There is a lack of local
      data on satisfaction and QoL among cancer patients receiving palliative treatment
      in Malaysia. This study covers patients with incurable, progressive cancer
      disease receiving palliative treatment in a teaching hospital in Kuala Lumpur,
      comparing the different components of QoL and correlations with patient
      satisfaction. A cross-sectional survey using Malay validated SF36 QoL and PSQ-18
      (Short Form) tools was carried out between July 2012 -January 2013 with 120
      cancer patients receiving palliative treatment, recruited into the study after
      informed consent using convenient sampling. Results showed that highest
      satisfaction were observed in Communication Aspect (50.6+/-9.07) and the least in
      General Satisfaction (26.4+/-5.90). The Mental Component Summary (44.9+/-6.84)
      scored higher when compared with the Physical Component Summary (42.2+/-7.91). In
      this study, we found that patient satisfaction was strongly associated with good
      quality of life among cancer patients from a general satisfaction aspect
      (r=0.232). A poor significant negative correlation was found in Physical
      Component (technical quality, r=-0.312). The Mental Component showed there was a
      poor negative correlation between time spent with doctor (r=-0.192) and
      accessibility, (r=-0.279). We found that feeling at peace and having a sense of
      meaning in life were more important to patients than being active or achieving
      good physical comfort. More studyis needed to investigate patients who score
      poorly on physical and mental component aspects to understand their needs in
      order to achieve better cancer care. 

PMID- 24568482
TI  - Safety and efficacy of sequential transcatheter arterial chemoembolization and
      portal vein embolization prior to major hepatectomy for patients with HCC.
AB  - OBJECTIVE: To evaluate the safety and efficacy of sequential transcatheter
      arterial chemoembolization (TACE )and portal vein embolization (PVE) before major
      hepatectomy for patients with hepatocellur carcinoma (HCC). METHODS: In this
      retrospective case-control study, data were collected from patients who underwent
      sequential TACE and PVE prior to major hemihepactectomy. Liver volumes were
      measured by computed tomography volumetry before TACE, and preoperation to assess
      degree of future remnant liver (FRL) hypertrophy and to check whether intro- or
      extrohepatic metastasis existed. Liver function was monitored by biochemistry
      after TACE, prior to and after major hepatectomy. RESULTS: Mean average FRL
      volume increased 32.3-71.4% (mean 55.4%) compared with preoperative FRL volume.
      After TACE, liver enzymes were elevated, but returned to normal in four weeks.
      During PVE and resection, no patient had intro- or extrohepatic metastasis.
      CONCLUSION: Sequential TACE and PVE is an effective method to improve resection
      opportunity, expand the scope of surgical resection, and greatly reduce
      postoperative intra- and extrahepatic metastasis.

PMID- 24568483
TI  - Outcomes based on risk assessment of anastomotic leakage after rectal cancer
      surgery.
AB  - PURPOSE: Anastomotic leakage (AL) is associated with high morbidity and
      mortality, high reoperation rates, and increased hospital length of stay. Here we
      investigated the risk factors for AL after anterior resection for rectal cancer
      with a double stapling technique. PATIENTS AND METHODS: Data for 460 patients who
      underwent primary anterior resection with a double stapling technique for rectal
      carcinoma at a single institution from 2003 to 2007 were prospectively collected.
      All patients experienced a total mesorectal excision (TME) operation. Clinical AL
      was defined as the presence of leakage signs and confirmed by diagnostic work-up
      according to ICD-9 codes 997.4, 567.22 (abdominopelvic abscess), and 569.81
      (fistula of the intestine). Univariate and logistic regression analyses of 20
      variables were undertaken to determine risk factors for AL. Survival was analysed
      using the Cox regression method. RESULTS: AL was noted in 35 (7.6%) of 460
      patients with rectal cancer. Median age of the patients was 65 (50-74) and 161
      (35%) were male. The diagnosis of AL was made between the 6th and 12th
      postoperative day (POD; mean 8th POD). After univariate and multivariate
      analysis, age (p=0.004), gender (p=0.007), tumor site (p<0.001), preoperative
      body mass index (BMI) (p<0.001), the reduction of TSGF on 5th POD less than
      10U/ml (p=0.044) and the pH value of pelvic dranage less than or equal to 6.978
      on 3rd POD (p<0.001) were selected as 6 independent risk factors for AL. It was
      shown that significant differences in survival of the patients were AL-related
      (p<0.001), high ASA score related (p=0.036), high-level BMI related (p=0.007) and
      advanced TNM stage related (p<0.001). CONCLUSIONS: AL after anterior resection
      for rectal carcinoma is related to advanced age, low tumor site, male sex, high
      preoperative BMI, low pH value of pelvic drainage on POD 3 and a significant
      reduction of TSGF on POD 5. In addition to their high risk of immediate
      postoperative morbidity and mortality, AL, worse physical status, severe obesity
      and advanced TNM stage have similarly negative impact on survival.

PMID- 24568484
TI  - Does HBV infection increase risk of endometrial carcinoma?
AB  - OBJECTIVE: Connections between chronic inflammation and tumor development and
      progression are now generally accepted. Recent evidence indicates that hepatitis
      B is associated with several types of cancer, but whether endometrial carcinoma
      (EC) is included has not been reported. METHODS: We analyzed HBV serum marker
      status in 398 patients with endometrial cancer, comparing them to 788 control
      women undergoing health examination. RESULTS: The total prevalence of HBsAg
      tested positive in cancer group was significantly higher than the control group
      (12.8% vs 6.0%, P=0.001), while positive HBsAb was significantly lower (41.2% vs
      68.5%, P=0.001). Hepatitis B carriers in endometrial cancer group were also more
      frequent than in the control group (9.3% vs 5.5%, P=0.013). Interestingly, in the
      endometrial cancer group, 147 cases were HBV serum marker negative, which was
      also higher than in the control group (36.9% vs 15.6%, P=0.001). CONCLUSION:
      There may be a correlation between HBV infection and endometrial carcinoma.

PMID- 24568485
TI  - p53 codon 72 polymorphism interactions with dietary and tobacco related habits
      and risk of stomach cancer in Mizoram, India.
AB  - BACKGROUND: This study was carried out to investigate the interaction of p53
      codon 72 polymorphism, dietary and tobacco habits with reference to risk of
      stomach cancer in Mizoram, India. A total of 105 histologically confirmed stomach
      cancer cases and 210 age, sex and ethnicity matched healthy population controls
      were included in this study. MATERIALS AND METHODS: The p53 codon 72 polymorphism
      was detected by PCR-RFLP and sequencing. H. pylori infection status was
      determined by ELISA. Information on various dietary and tobacco related habits
      was recorded with a standard questionnaire. RESULTS: This study revealed that
      overall, the Pro/ Pro genotype was significantly associated with a higher risk of
      stomach cancer (OR, 2.54; 95%CI, 1.01-6.40) as compared to the Arg/Arg genotype.
      In gender stratified analysis, the Pro/Pro genotype showed higher risk (OR, 7.50;
      95%CI, 1.20-47.0) than the Arg/Arg genotype among females. Similarly, the Pro/Pro
      genotype demonstrated higher risk of stomach cancer (OR, 6.30; 95%CI, 1.41-28.2)
      among older people (>60 years). However, no such associations were observed in
      males and in individuals <60 years of age. Smoke dried fish and preserved meat
      (smoke dried/sun dried) consumers were at increased risk of stomach cancer (OR,
      4.85; 95%CI, 1.91-12.3 and OR, 4.22; 95%CI, 1.46-12.2 respectively) as compared
      to non-consumers. Significant gene-environment interactions exist in terms of p53
      codon 72 polymorphism and stomach cancer in Mizoram. Tobacco smokers with Pro/Pro
      and Arg/Pro genotypes were at higher risk of stomach cancer (OR, 16.2; 95%CI,
      1.72-153.4 and OR, 9.45; 95%CI, 1.09-81.7 respectively) than the non-smokers
      Arg/Arg genotype carriers. The combination of tuibur user and Arg/Pro genotype
      also demonstrated an elevated risk association (OR, 4.76; 95%CI, 1.40-16.21).
      CONCLUSIONS: In conclusion, this study revealed that p53 codon 72 polymorphism
      and dietary and tobacco habit interactions influence stomach cancer development
      in Mizoram, India.

PMID- 24568486
TI  - Responsibilities and difficulties of caregivers of cancer patients in home care.
AB  - BACKGROUND: From having been known as a virulent disease in 1970s, cancer is now
      considered a chronic disease and about two thirds of cancer patients live for
      five years after diagnosis. Home care has gradually gained more importance and it
      is a great burden on the shoulders of caregivers. Caregivers have to undertake
      the responsibility of the cancer patient's home management, and organize care and
      arrange health care services according to the ever-changing condition of
      patients. Caregivers should be prepared for home care so they can provide
      accurate and complete care. This descriptive study aimed to investigate
      challenges that caregivers encounter in the home care of patients and the reasons
      for these challenges. MATERIALS AND METHODS: The research group consisted of
      caregivers of outpatients in a daily treatment center in a university hospital.
      The research sample consisted of 137 voluntary caregivers of patients who
      attended the Daily Treatment Center for control, chemotherapy or other supportive
      cares services between January-June, 2011. Data were collected with face-to-face
      interviews in the Daily Treatment Center. Ethics Committee approval was taken
      from the university hospital; caregivers and their patients were informed about
      the research and their approval was obtained as well. RESULTS: It was found that
      54.0% of caregivers helped with patient's nutrition, 50.4% with medicine use,
      26.3% with oral hygiene, 26.3% with meeting urinary needs and 51.8% with changing
      clothes. In addition, 69.3% of caregivers helped to change bed sheets, 38.7%
      assisted patients to communicate with their environment and 71.5% to bring the
      patient to hospital or outside. CONCLUSIONS: In this study, it was found that
      Turkish caregivers experience challenges due to following factors: patient
      nutrition, medicine use, oral and body hygiene, colostomy maintenance and stomach
      tube feeding, concern of dropping the patient, feeling incompetence in body
      temperature and fever control, fatigue, and lack of personal time.

PMID- 24568487
TI  - Randomized control study of nedaplatin or cisplatin concomitant with other
      chemotherapy in the treatment of advanced non-small cell lung cancer.
AB  - OBJECTIVE: To observe the short-term efficacy, long-term survival time and
      adverse responses with nedaplatin (NDP) or cisplatin (DDP) concomitant with other
      chemotherapy in treating non-small cell lung cancer. MATERIALS AND METHODS: A
      retrospective, randomized, control study was conducted, in which 619 NSCLC
      patients in phases III and IV who were initially treated and re-treated were
      randomly divided into an NDP group (n=294) and a DDP group (n=325), the latter
      being regarded as controls. Chemotherapeutic protocols (CP/DP/GP/NP/TP)
      containing NDP or DDP were given to both groups. Patients in both groups were
      further divided to evaluate the clinical efficacies according to initial and re
      treatment stage, pathological pattern, type of combined chemotherapeutic
      protocols, tumor stage and surgery. RESULTS: The overall response rate (ORR) and
      disease control rate (DCR) in the NDP group were 48.6% and 95.2%, significantly
      higher than in the DDP group at 35.1% and 89.2%, respectively (P<0.01). In NSCLC
      patients with initial treatment, squamous carcinoma and phase III, there were
      significant differences in ORR and DCR between the groups (P<0.05), while ORR was
      significant in patients with adenocarcinoma, GP/TP and in phase IIIa (P<0.05).
      There was also a significant difference in DCR in patients in phase IIIb
      (P<0.05). According to the statistical analysis of survival time of all patients
      and of those in clinical phase III, the NDP group survived significantly longer
      than the DDP group (P<0.01). The rates of decreased hemoglobin and increased
      creatinine, nausea and vomiting in the NDP group were evidently lower than in DDP
      group (P<0.05). CONCLUSION: NDP concomitant with other chemotherapy is effective
      for treating NSCLC, with higher clinical efficacy than DDP concomitant with
      chemotherapy, with advantages in prolonging survival time and reducing toxic and
      adverse responses.

PMID- 24568488
TI  - Effect of grape procyanidins on tumor angiogenesis in liver cancer xenograft
      models.
AB  - BACKGROUND: In recent years a wide variety of flavonoids or polyphenolic
      substances have been reported to possess substantial anti-carcinogenic and
      antimutagenic activities. Grape proanthocyanidins (GPC) are considered as good
      examples for which there is evidence of potential roles as anti-carcinogenic
      agents. METHODS: A xenograft model was established using H22 cells subcutaneously
      injected into mice and used to assess different concentrations of grape
      proanthocyanidins (GPC) and Endostar. Treatments were maintained for 10 days,
      then levels of vascular endothelial growth factor (VEGF) and microvessel density
      (MVD) were examined by immunohistochemistry, while VEGF mRNA was determined by
      real-time PCR in tumor tissue. RESULTS: The expression of MVD and VEGF decreased
      gradually as the concentration of GPC increased.There was a significant positive
      correlation between MVD and VEGF. CONCLUSIONS: These results suggest that GPC
      restrains the growth of tumor, possibly by inhibiting tumour angiogenesis.

PMID- 24568489
TI  - Mechanisms of hela cell apoptosis induced by abnormal Savda Munziq total
      phenolics combined with chemotherapeutic agents.
AB  - OBJECTIVE: To investigate the effects of abnormal Savda Munziq (ASMq) total
      phenolics combined with cisplatin and docetaxel on the Hela cell growth. METHODS:
      In vivo cultured Hela cells were treated with cisplatin, docetaxel, total
      phenolics, cisplatin+total phenolics or docetaxel+total phenolics. MTT was
      performed to assess inhibition of cell proliferation, flow cytometry to detect
      apoptosis, and semi-quantitative RT-PCR to test for survivin and Bcl-2
      expression. RESULTS: The total phenolics, cisplatin and docetaxel had significant
      inhibitory and apoptosis-promoting effects on Hela cells (P<0.05), with the early
      apoptotic rates of 12.8+/-0.70%, 18.9+/-3.79% and 15.8+/-3.8)%; the total
      phenolics, cisplatin and docetaxel significantly decreased the expression of Bcl
      2 and survivin (all P<0.01), especially when used in combination. CONCLUSION:
      ASMq total phenolics, combined with cisplatin and docetaxel, could promote the
      apoptosis of Hela cells possibly through reducing the expression of Bcl-2 and
      survivin.

PMID- 24568490
TI  - Purple rice extract supplemented diet reduces DMH- induced aberrant crypt foci in
      the rat colon by inhibition of bacterial beta-glucuronidase.
AB  - BACKGROUND: Purple rice has become a natural product of interest which is widely
      used for health promotion. This study investigated the preventive effect of
      purple rice extract (PRE) mixed diet on DMH initiation of colon carcinogenesis.
      MATERIALS AND METHODS: Rats were fed with PRE mixed diet one week before
      injection of DMH (40 mg/kg of body weight once a week for 2 weeks). They were
      killed 12 hrs after a second DMH injection to measure the level of O6
      methylguanine and xenobiotic metabolizing enzyme activities. RESULTS: In rats
      that received PRE, guanine methylation was reduced in the colonic mucosa, but not
      in the liver, whereas PRE did not affect xenobiotic conjugation, with reference
      to glutathione-S-transferase or UDP-glucuronyl transferase. After 5 weeks, rats
      that received PRE with DMH injection had fewer ACF in the colon than those
      treated with DMH alone. Interestingly, a PRE mixed diet inhibited the activity of
      bacterial beta-glucuronidase in rat feces, a critical enzyme for free
      methylazoxymethanol (MAM) release in the rat colon. These results indicated that
      purple rice extract inhibited beta-glucuronidase activity in the colonic lumen,
      causing a reduction of MAM-induced colonic mucosa DNA methylation, leaded to
      decelerated formation of aberrant crypt foci in the rat colon. CONCLUSIONS: The
      supplemented purple rice extract might thus prevent colon carcinogenesis by the
      alteration of the colonic environment, and thus could be further developed for
      neutraceutical products for colon cancer prevention.

PMID- 24568491
TI  - Prevalence of potentially malignant oral mucosal lesions among tobacco users in
      Jeddah, Saudi Arabia.
AB  - Smoking is recognized as a health problem worldwide and there is an established
      tobacco epidemic in Saudi Arabia as in many other countries, with tobacco users
      at increased risk of developing many diseases. This cross sectional study was
      conducted to assess the prevalence of oral mucosal, potentially malignant or
      malignant, lesions associated with tobacco use among a stratified cluster sample
      of adults in Jeddah, Saudi Arabia. A sample size of 599 was collected and each
      participant underwent clinical conventional oral examination and filled a
      questionnaire providing information on demographics, tobacco use and other
      relevant habits. The most common form of tobacco used was cigarette smoking (65.6
      %) followed by Shisha or Moasel (38.1%), while chewing tobacco, betel nuts and
      gat accounted for 21-2%, 7.7%, and 5% respectively. A high prevalence (88.8%) of
      soft tissue lesions was found among the tobacco users examined, and a wide range
      of lesions were detected, about 50% having hairy tongue, 36% smoker's melanosis,
      28.9% stomatitis nicotina, 27% frictional keratosis, 26.7% fissured tongue, 26%
      gingival or periodontal inflammation and finally 20% leukodema. Suspicious
      potentially malignant lesions affected 10.5% of the subjects, most prevalent
      being keratosis (6.3%), leukoplakia (2.3%), erythroplakia (0.7%), oral submucous
      fibrosis (0.5%) and lichenoid lesions (0.4%), these being associated with male
      gender, lower level of education, presence of diabetes and a chewing tobacco
      habit. It is concluded that smoking was associated with a wide range of oral
      mucosal lesions , those suspicious for malignancy being linked with chewable
      forms, indicating serious effects.

PMID- 24568492
TI  - Equivocal association of RAD51 polymorphisms with risk of esophageal squamous
      cell carcinoma in a Chinese population.
AB  - AIM: To study the contribution of genetic variation in RAD51 to risk of
      esophageal squamous cell carcinoma (ESCC). METHODS: Three single nucleotide
      polymorphisms (SNPs) in RAD51 (rs1801320, rs4144242 and rs4417527) were genotyped
      in 316 ESCC patients and 316 healthy controls in Anyang area of China using PCR-
      RFLP (polymerase chain reaction-restriction fragment length polymorphism).
      Demographic variables between cases and controls were statistically compared by T
      test and Chi-square test. Hardy-Weinberg equilibrium was evaluated by the Chi
      square test. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated
      to measure any association with ESCC. Haplotype frequencies were estimated by
      Phase 2.1. RESULT: The genotype frequencies of rs1801320, rs4144242 and rs4417527
      in patients with ESCC demonstrated no significant differences from those in
      control group (P>0.05). When the haplotypes of these three SNPs were constructed
      and their relationships with ESCC risk investigated, however, CGG was observed to
      increase the risk (P=0.020, OR=2. 289). CONCLUSIONS: There was no association
      between the three SNPs of RAD51 and ESCC susceptibility in our Chinese
      population. However, the CGG haplotype might be a risk factor.

PMID- 24568493
TI  - Fangchinoline inhibits cell proliferation via Akt/GSK-3beta/ cyclin D1 signaling
      and induces apoptosis in MDA-MB-231 breast cancer cells.
AB  - Fangchinoline (Fan) inhibits cell proliferation and induces apoptosis in several
      cancer cell lines. The effects of Fan on cell growth and proliferation in breast
      cancer cells remain to be elucidated. Here, we show that Fan inhibited cell
      proliferation in the MDA-MB-231 breast cancer cell line through suppression of
      the AKT/Gsk- 3beta/cyclin D1 signaling pathway. Furthermore, Fan induced
      apoptosis by increasing the expression of Bax (relative to Bcl-2), active caspase
      3 and cytochrome-c. Fan significantly inhibited cell proliferation of MDA- MB-231
      cells in a concentration and time dependent manner as determined by MTT assay.
      Flow cytometry analysis demonstrated that Fan treatment of MDA-MB-231 cells
      resulted in cell cycle arrest at the G1 phase, which correlated with apparent
      downregulation of both mRNA and protein levels of both PCNA and cyclin D1.
      Further analysis demonstrated that Fan decreased the phosphorylation of AKT and
      GSK-3beta. In addition, Fan up-regulated active caspase3, cytochrome-c protein
      levels and the ratio of Bax/Bcl-2, accompanied by apoptosis. Taken together,
      these results suggest that Fan is a potential natural product for the treatment
      of breast cancer. 

PMID- 24568494
TI  - Low counts of gammadelta T cells in peritumoral liver tissue are related to more
      frequent recurrence in patients with hepatocellular carcinoma after curative
      resection.
AB  - OBJECTIVES: TCR- gamma-delta + T cells (gammadelta T cells) are non-conventional
      T lymphocytes that can recognize and eradicate tumor cells. Our previous studies
      showed that infiltration and function of gammadeltaT cells were substantially
      attenuated in hepatocellular carcinoma (HCC). However, their prognostic value was
      not clarified. METHODS: The association between gammadelta T cells and the
      clinical outcomes was determined by immunohistochemistry (IHC) in a HCC patient
      cohort (n = 342). RESULTS: Immunohistochemistry showed decreased infiltration of
      gammadelta T cells in tumoral tissues compared with paired peritumoral tissues.
      The counts of gammadelta T cells in peritumoral tissues were negatively
      correlated with tumor size (P = 0.005). Survival analysis showed that the levels
      of peritumoral gammadelta T cells were related to both time to recurrence (TTR)
      and overall survival (OS) (P = 0.010 and P = 0.036, respectively) in univariate
      analysis, and related to TTR in multivariate analysis (P = 0.014, H.R. [95% CI] =
      0.682 [0.502-0.927]). Furthermore, the level of peritumoral gammadelta T cells
      showed independent prognostic value for TTR in Barcelona Clinic Liver Cancer
      (BCLC) stage A patients (P = 0.038, H.R. [95% CI] = 0.727 [0.537-0.984]).
      However, tumoral gammadelta T cells did not show independent prognostic value for
      either TTR or OS in HCC patients. CONCLUSIONS: Low counts of gammadelta T cells
      in peritumoral liver tissue are related to a higher incidence of recurrence in
      HCC and can predict postoperative recurrence, especially in those with early
      stage HCC.

PMID- 24568495
TI  - Maternal factors and risk of childhood leukemia.
AB  - BACKGROUND: Although the cause in most cases of childhood leukemia is not known,
      the contribution of environmental risk factors in the context of genetic
      predisposition has been reported with inconsistent results. The aim of this study
      was to examine association of childhood leukemia with maternal factors especially
      during pregnancy, to help in avoiding risk factors. MATERIALS AND METHODS: This
      case-control study included children younger than 18 years diagnosed with
      leukemia from 2008 to 2012. Controls were randomly selected and individually
      matched to cases with respect to age, sex, and residency. All variables were
      compared between cases and control to determine any significant association with
      leukemia. RESULTS: Statistically significant associations between risk of
      childhood leukemia with mother's education (p=0.001), occupation (p=0.0005) and
      pesticides exposure (p=0.005) during pregnancy were found. However, there were no
      significant links with maternal age (p=0.090), history of fetal loss (0.85),
      history of radiography during pregnancy (p=0.400), history of drug intake
      (p=0.689) and infection (p=0.696) during pregnancy. CONCLUSIONS: The results
      showed increased risk of leukemia in children whose mothers were working in
      agriculture and were exposed to pesticides during pregnancy. The further study
      needs to be investigated to know association of various maternal risk factors
      with leukemia which remained unknown in this study.

PMID- 24568496
TI  - Anticancer properties of Teucrium persicum in PC-3 prostate cancer cells.
AB  - Crude extracts or phytochemicals obtained from some plants have potential anti
      cancer properties. Teucrium persicum is an Iranian endemic plant belonging to the
      Lamiaceae family which has traditionally been used to relieve abdominal pains.
      However, the anti-cancer properties of this species of the Teucrium genus have
      not been investigated previously. In this study, we have used a highly invasive
      prostate cancer cell line, PC-3, which is an appropriate cell system to study
      anti-tumor properties of plants. A methanolic extract obtained from T persicum
      potently inhibited viability of PC-3 cells. The viability of SW480 colon and T47D
      breast cancer cells was also significantly decreased in the presence of the T
      persicum extract. Flow cytometry suggested that the reduction of cell viability
      was due to induction of apoptosis. In addition, the results of wound healing and
      gelatin zymography experiments supported anti-cell invasion activity of T
      persicum. Interestingly, sublethal concentrations of T persicum extract induced
      an epithelial-like morphology in a subpopulation of cells with an increase in E
      Cadherin and beta-Catenin protein levels at the cell membrane. These results
      strongly suggest that T persicum is a plant with very potent anti-tumor activity.

PMID- 24568497
TI  - Possible effect of implementing a national query program on site-specific cancer
      mortality rates in Taiwan.
AB  - BACKGROUND: This study aimed to examine possible effects of implementing a
      national query program on site-specific cancer mortality rates. MATERIALS AND
      METHODS: A total of 2,874 query letters were sent out by the Department of
      Statistics, Ministry of Health and Welfare of Taiwan between January 2009 and
      December 2011 to medical certifiers who reported "neoplasm with uncertain nature"
      on the death certificate asking for more detailed information for coding.
      RESULTS: Of the 2,571 responses, in 1,398 cases (54%) medical certifiers were
      still unable to determine the nature of the neoplasm. There were four neoplasm
      sites for which more than 50% of the responses changed the category to malignant,
      the gastrointestinal system (73%), urinary system (60%), stomach (55%) and rectum
      (53%). The liver was the cancer site that showed the largest absolute increase in
      the number of deaths after the query; however, the brain showed the largest
      relative increase, at 12%. CONCLUSIONS: Different neoplasm sites showed different
      magnitudes of change in nature after the query. Brain cancer mortality rates
      exhibited the largest increase.

PMID- 24568498
TI  - Cellular mechanisms of a new pyrazinone compound that induces apoptosis in SKOV-3
      cells.
AB  - We screened a small molecular library that was designed and independently
      synthesized in vitro and found a new drug (MY-03-01) that is active against
      ovarian cancer. We established that MY-03-01 effectively inhibited SKOV-3 cell
      survival in a dose-dependent manner, based on cell viability rates, and that it
      not only induced SKOV-3 apoptosis by itself, but also did so synergistically with
      paclitaxel. Secondly, when MY-03-01 was applied at 40 MUM, its hemolytic activity
      was less than 10%, compared with the control, and there was almost no damage to
      normal cells at this concentration. In addition, we used DAPI staining and flow
      cytometry to show that MY- 03-01 could significantly induce apoptosis of SKOV-3
      cells. Finally, we found that MY-03-01 likely induced SKOV-3 apoptosis by
      activating caspase3 and caspase9 through the mitochondrial pathway. 

PMID- 24568499
TI  - Non-association of IL-16 rs4778889 T/C polymorphism with cancer risk in Asians: a
      meta-analysis.
AB  - The IL-16 rs4778889 T/C polymorphism is associated with cancer risk. However, the
      results are conflicting. We performed this meta-analysis to derive a more precise
      estimation of the relationship. A comprehensive literature search was performed
      using PubMed, Embase and Web of Science databases. Odds ratio (OR) and 95%
      confidence interval (CI) were used to assess the strength of association. A total
      of 6 studies including 1,603 cases and 2,342 controls were identified. With all
      studies involved, results showed no statistically significant association between
      IL-16 rs4778889 T/C polymorphism and cancer risk (CC vs. CT+TT: OR=0.74, 95%CI:
      0.55-1.02, Ph=0.15; CC+CT vs. TT: OR=0.89, 95%CI: 0.72-1.10, Ph =0.03; CC vs. TT:
      OR=0.73, 95%CI: 0.53- 1.00, Ph =0.08; CT vs. TT: OR=0.91, 95%CI: 0.79-1.05, Ph
      =0.08; C vs. T: OR=0.89, 95%CI: 0.74-1.07, Ph =0.02). In addition, the results
      were not changed when studies were stratified by cancer type. However, to verify
      our findings, it is essential to perform more well-designed studies with larger
      sample sizes in the future. 

PMID- 24568501
TI  - Institutional experience of interstitial brachytherapy for head and neck cancer
      with a comparison of high- and low dose rate practice.
AB  - AIMS: To describe our institutional experience with high dose rate (HDR)
      interstitial brachytherapy (IBT) compared with previously reported results on the
      low dose rate (LDR) practice for head and neck cancer. MATERIALS AND METHODS:
      Eighty-four patients with oral cavity (n=70) or oropharyngeal cancer (n=14) were
      treated with 192Ir HDR-IBT. Seventy-eight patients had stage I or II tumour. The
      patients treated with IBT alone (n=42) received 39-42 Gy/10-14 fractions
      (median=40 Gy/10 fractions). With respect to the combination therapy group
      (n=42), prescription dose comprised of 12-18 Gy/3-6 fractions (median=15 Gy/5
      fractions) for IBT and 40-50 Gy/20-25 fractions (median=50 Gy/25 fractions) for
      external radiotherapy. Brachytherapy was given as 2 fractions per day 6 hours
      apart with 4 Gy per fraction for monotherapy and 3 Gy per fraction for
      combination therapy. RESULTS: Four patients were not evaluable in the analysis of
      outcome. The primary site relapse rates were 23.8% (10/42) and 68.4% (26/38) in
      patients treated with IBT alone and combination therapy, respectively (p<0.001).
      Salvage surgery was performed in 19 patients. The 5-year local control rate was
      estimated at 62% and the disease-free survival (DFS) rate at 52% for all
      patients. Local control with respect to T1 and T2 tumours was 84% and 42%,
      respectively. CONCLUSIONS: Our present series on HDR-IBT and the previous report
      on LDR-IBT for head and neck cancer demonstrated similar DFS rates at 5 years
      (52%). The rate of regional failure in node-negative patients was <20% in both of
      our series. HDR-IBT offers similar results to LDR-IBT for head and neck cancer.

PMID- 24568500
TI  - Reconsideration of clinical and histopathological prognostic factors in breast
      cancer patients: a single center experience.
AB  - BACKGROUND: The clinical course of the neoplasm may vary due to both patient and
      tumor cell characteristics. AIM: The aim of this study was to research the
      influence of certain clinical and pathological features on the prognosis of early
      stage breast cancer. MATERIALS AND METHODS: This study included 117 women that
      were treated and followed-up in between the years 2001-2011. The demographic,
      clinical and histopathological features of the cases were reviewed
      retrospectively. STATISTICAL ANALYSIS: In categorical comparisons between groups,
      cross-tab statistics were provided and significance levels were estimated using
      chi-square test. Cox regression analysis, Pearson and Spearman correlation tests,
      and the Kaplan-Meier test were also used. RESULTS: With an average of 35-months
      follow-up, the mean disease-free survival of patients was 91 months and the mean
      overall survival time was 132 months. In the whole study group, the disease-free
      survival rates were 88, 84, 83 and 52%, while the overall survival rates 95, 94,
      83, and 83% within the first, third, fifth and tenth years, respectively. The
      disease- free and overall survival rates were decreased with increasing tumor
      grades, though this was not statistically significant. The presence of
      lymphovascular invasion, positive staining with Ki67 and postmenopausal status
      were associated with shorter disease-free and overall survival times. In
      multivariate analysis, only age and Her2/ neu receptor status influenced the
      prognosis significantly. CONCLUSIONS: In parallel to clinical, histopathological,
      and immunohistochemical prognostic features in breast cancer, in this study
      positive Her2/neu receptor status, a previously accepted poor prognostic factor,
      was found to have positive influence after trastuzumab treatment.

PMID- 24568502
TI  - Vitamin D3 and beta-carotene deficiency is associated with risk of esophageal
      squamous cell carcinoma - results of a case-control study in China.
AB  - OBJECTIVE: The aim was to evaluate roles of vitamin D3 (VD3) and beta-carotene
      (BC) in the development of esophageal squamous cell carcinoma (ESCC) in a high
      risk area, Huai'an District, Huai'an City, China. METHODS: 100 new ESCC diagnosed
      cases from 2007 to 2008 and 200 residency- age-, and sex-matched healthy controls
      were recruited. Data were collected from questionnaires, including a food
      frequency questionnaire (FFQ) to calculate the BC intake, and reversed phase high
      performance liquid chromatography (RP-HPLC) was used to measure the serum
      concentrations of BC and VD3. Odds ratios (OR) and 95% confidence intervals (CI)
      were calculated in conditional logistic regression models. RESULTS: The average
      dietary intake of BC was 3322.9 MUg (2032.4- 5734.3) in the case group and 3626.8
      MUg (1961.9-5827.9) in control group per capita per day with no significant
      difference by Wilcoxon test (p>0.05). However, the levels of VD3 and BC in the
      case group were significantly lower than in the control group (p<0.05). The OR
      values of the highest quartile and the lowest quartile of VD3 and BC in serum
      samples were both 0.13. CONCLUSION: Our results add to the evidence that high
      circulating levels of VD3 and BC are associated with a reduced risk of ESCC in
      this Chinese population.

PMID- 24568503
TI  - PDCD4 as a predictor of sensitivity to neoadjuvant chemoradiotherapy in locally
      advanced rectal cancer patients.
AB  - OBJECTIVE: The purpose of this study was to examine the role of programmed cell
      death 4 (PDCD4) expression in predicting tumor response to neoadjuvant
      chemoradiotherapy and outcomes for patients with locally advanced rectal cancer.
      METHODS: Clinicopathological factors and expression of PDCD4 were evaluated in 92
      patients with LARC treated with nCRT. After the completion of therapy, 4 cases
      achieved clinical complete response (cCR), and thus the remaining 88 patients
      underwent a standardized total mesorectal excision procedure. There were 38
      patients (41.3%) with a good response (TRG 3-4) and 54 (58.7%) with a poor one
      (TRG 0-2). RESULTS: Immunohistochemical staining analyses showed that patients
      with high expression of PDCD4 were more sensitive to nCRT than those with low
      PDCD4 expression (P=0.02). High PDCD4 expression before nCRT and good response
      (TRG3-4) were significantly associated with improved 5-year disease-free survival
      and 5-year overall survival (P<0.05). Multivariate analysis demonstrated that the
      pretreatment PDCD4 expression was an independent prognostic factor. CONCLUSION:
      Our study demonstrated that high expression of PDCD4 protein is a useful
      predictive factor for good tumor response to nCRT and good outcomes in patients
      with LARC.

PMID- 24568504
TI  - Predictors of outcome in patients with advanced nonseminomatous germ cell
      testicular tumors.
AB  - BACKGROUND: Predictor factors determining complete response to treatment are
      still not clearly defined. We aimed to evaluate clinicopathological features,
      risk factors, treatment responses, and survival analysis of patient with advanced
      nonseminomatous GCTs (NSGCTs). MATERIALS AND METHODS: Between November 1999 and
      September 2011, 140 patients with stage II and III NSGCTs were referred to our
      institutions and 125 patients with complete clinical data were included in this
      retrospective study. Four cycles of BEP regimen were applied as a first-line
      treatment. Salvage chemotherapy and/or high-dose chemotherapy (HDCT) with
      autologous stem cell transplantation were given in patients who progressed after
      BEP chemotherapy. Post-chemotherapy surgery was performed in selected patients
      with incomplete radiographic response and normal tumor markers. RESULTS: The
      median age was 28 years. For the good, intermediate and poor risk groups, compete
      response rates (CRR) were, 84.6%, 67.9% and 59.4%, respectively. Extragonadal
      tumors, stage 3 disease, intermediate and poor risk factors, rete testis invasion
      were associated with worse outcomes. There were 32 patients (25.6%) with non-CR
      who were treated with salvage treatment. Thirty-one patients died from GCTs and
      94% of them had stage III disease. CONCLUSIONS: Even though response rates are
      high, some patients with GCTs still need salvage treatment and cure cannot be
      achieved. Non-complete response to platinium-based first-line treatment is a
      negative prognostic factor. Our study confirmed the need for a prognostic and
      predictive model and more effective salvage approaches.

PMID- 24568505
TI  - Effect of NUCKS-1 overexpression on cytokine profiling in obese women with breast
      cancer.
AB  - BACKGROUND: Overweight and obesity are recognized as major drivers of cancers
      including breast cancer. Several cytokines, including interleukin-6 (IL-6), IL-10
      and lipocalin 2 (LCN2), as well as dysregulated cell cycle proteins are
      implicated in breast carcinogenesis. The nuclear, casein kinase and cyclin
      dependent kinase substrate-1 (NUCKS-1), is a nuclear DNA-binding protein that has
      been implicated in several human cancers, including breast cancer. OBJECTIVES:
      The present study was conducted to evaluate NUCKS-1 mRNA expression in breast
      tissue from obese patients with and without breast cancer and lean controls.
      NUCKS-1 expression was correlated to cytokine profiles as prognostic and
      monitoring tools for breast cancer, providing a molecular basis for a causal link
      between obesity and risk. MATERIALS AND METHODS: This study included 39 females
      with breast cancer (G III) that was furtherly subdivided into two subgroups
      according to cancer grading (G IIIa and G IIIb) and 10 control obese females (G
      II) in addition to 10 age-matched healthy lean controls (G I). NUCKS-1 expression
      was studied in breast tissue biopsies by means of real-time PCR (RT-PCR). Serum
      cytokine profiles were determined by immunoassay. Lipid profiles and glycemic
      status as well as anthropometric measures were also recorded for all
      participants. RESULTS: IL-6, IL-12 and LCN2 were significantly higher in control
      obese and breast cancer group than their relevant lean controls (p<0.05), while
      NUCKS-1 mRNA expression was significantly higher in the breast cancer group
      compared to the other groups (p<0.05). Significant higher levels of IL-6, IL-12,
      and LCN2 as well as NUCKS-1 mRNA levels were reported in G IIIb than G IIIa, and
      positively correlated with obesity markers in all obese patients. CONCLUSIONS:
      Evaluation of cytokine levels as well as related gene expression may provide a
      new tool for understanding interactions for three axes of carcinogenesis, innate
      immunity, inflammation and cell cycling, and hope for new strategies of
      management.

PMID- 24568506
TI  - Association between VDR polymorphisms and breast cancer: an updated and
      comparative meta-analysis of crude and adjusted odd ratios.
AB  - There is a lot of debate on the relationship between vitamin D receptor
      polymorphisms and risk of breast cancer. Herein, we quantitatively analyzed the
      published case-control studies on this relationship by meta- analysis, performing
      a bibliographic search from Pubmed and CNKI up to July 31, 2013. The included
      case- control studies for Fok1, Bsm1, Taq1, Apa1, Cdx2 and Poly-A were 16, 19,
      20, 10, 4, 6, respectively. Crude and adjusted odd ratios and 95% confidence
      intervals were calculated to present and compare the strength of any
      associations. The results of combined analyses indicated that Fok1, Bsm1, Apa1,
      Cdx2 and Poly-A were not significantly associated with the risk of breast cancer.
      In contrast, the tt genotype of Taq1 was a modest risk factor for breast cancer
      development (tt vs. TT: OR = 1.21, 95% CI: 1.01-1.44). To further confirm the
      above results, adjusted effects for the six polymorphisms were pooled based on
      adjusted ORs reported in the original studies. Adjusted ORs of Fok1, Apa1, Cdx2
      and Poly-A were similar to the crude ORs. However, Bsm1 and Taq1 showed
      inconsistent results. For Bsm1, OR for BB vs. bb was 0.85, 95% CI: 0.74-0.98; for
      Taq1, OR for tt vs. TT was 1.03, 95% CI: 0.92-1.15, and not associated with risk.
      Subgroup analyses for crude ORs showed some association between Bsm1, Taq1 and
      breast cancer in Caucasians only, but for adjusted ORs, no associations were
      found. This meta-analysis suggests that the roles that Fok1, Apa1, Cdx2 and Poly
      A polymorphisms play in breast cancer risk are negligible, with Bsm1 and Taq1 as
      possible exceptions. To be conservative, we still assumed that they may play a
      modest role in determining breast cancer risk. Further studies are needed to
      validate our findings. 

PMID- 24568507
TI  - Shorter distance between the nodule and capsule has greater risk of cervical
      lymph node metastasis in papillary thyroid carcinoma.
AB  - BACKGROUND: The purpose of this study was to assess the relationship between
      different sonographic features of papillary thyroid carcinoma (PTC) on high
      frequency ultrasound and cervical lymph node metastasis (CLNM). MATERIALS AND
      METHODS: We enrolled 548 patients who underwent initial surgery for PTC between
      May 2011 and December 2012 in our hospital at diagnosis. The sonographic features
      of 513 PTC nodules in 513 eligible patients, who had single PTC nodules in their
      thyroid glands, were retrospectively investigated. All patients with a suspect
      malignant nodule (d<0.5cm) among multiple nodules were initially diagnosed by
      fine-needle aspiration biopsy (FNAB) to ascertain if the suspect nodule was PTC.
      The final diagnosis of all the thyroid nodules and existence of CLNM were based
      on postoperative pathology. Patients were divided into two groups: a positive
      group with CLNM (224 nodules) and a negative group without CLNM (289 nodules).
      The following factors were investigated: gender, age, echogenicity, echotexture,
      size, shape, location, margin, contour, calcification morphology, distance
      between the nodule and pre- or post-border of the thyroid capsule, vascularity
      and the differences between the two groups. RESULTS: Correlation analysis showed
      that shorter distances between the nodule and pre- or post- border of thyroid
      capsule resulted in greater risk of CLNM (Spearman correlation coefficient=-0.22,
      p<0.0001). The significant factors in multivariate analysis were age<45yrs,
      larger size (d>1cm), "wider than tall" shape, extrathyroid extension and mixed
      flow (internal and peripheral) (p<0.05, OR=0.406, 2.093, 0.461, 1.610, 1.322).
      CONCLUSIONS: Significant sonographic features of PTC nodules in preoperative high
      frequency ultrasound are crucial for predicting CLNM.

PMID- 24568508
TI  - Hybrid capture 2 assay based evaluation of high-risk HPV status in healthy women
      of north-east India.
AB  - BACKGROUND: High risk HPV (HR-HPV) testing has been recommended as an effective
      tool along with cytology screening in identification of cervical intraepithelial
      lesions (CINs) and prevention of their progress towards invasive cervical cancer.
      The aim of this study was to assess the HR-HPV DNA status by Hybrid Capture 2
      (HC2) assay in healthy asymptomatic women of North-East India. MATERIALS AND
      METHODS: This study examined cervical cell samples of forty three (n=43) healthy
      women by HC2 assay. A High Risk HPV DNA kit (Qiagen) was used which can detect 13
      high risk HPV types: 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and 68.
      RESULTS: The mean relative light units (RLU) for samples was in the range of 141
      5, 94, 619. HR-HPV DNA was confirmed in 16% (7/43) of participant women samples.
      Among demographic and clinical parameters, menstrual irregularity (p=0.039) and
      infection history (p=0.028) has shown statistically significant differences
      between the HR-HPV-positive and negative groups. In the HR-HPV positive group,
      two women were confirmed for CINs after colposcopy and histopathologic
      examination. CONCLUSIONS: We suggest that there may be an association between
      irregular menstruation and infection history of the urogenital tract with HR-HPV
      DNA prevalence in North-East Indian asymptomatic women. HC2 assay can be a
      valuable tool for HR-HPV screening.

PMID- 24568509
TI  - Surveying and optimizing the predictors for ependymoma specific survival using
      SEER data.
AB  - PURPOSE: This study used receiver operating characteristic curve to analyze
      Surveillance, Epidemiology and End Results (SEER) ependymoma data to identify
      predictive models and potential disparity in outcome. MATERIALS AND METHODS: This
      study analyzed socio-economic, staging and treatment factors available in the
      SEER database for ependymoma. For the risk modeling, each factor was fitted by a
      Generalized Linear Model to predict the outcome ('brain and other nervous
      systems' specific death in yes/no). The area under the receiver operating
      characteristic curve (ROC) was computed. Similar strata were combined to
      construct the most parsimonious models. A random sampling algorithm was used to
      estimate the modeling errors. Risk of ependymoma death was computed for the
      predictors for comparison. RESULTS: A total of 3,500 patients diagnosed from 1973
      to 2009 were included in this study. The mean follow up time (S.D.) was 79.8
      (82.3) months. Some 46% of the patients were female. The mean (S.D.) age was 34.4
      (22.8) years. Age was the most predictive factor of outcome. Unknown grade
      demonstrated a 15% risk of cause specific death compared to 9% for grades I and
      II, and 36% for grades III and IV. A 5-tiered grade model (with a ROC area 0.48)
      was optimized to a 3-tiered model (with ROC area of 0.53). This ROC area tied for
      the second with that for surgery. African-American patients had 21.5% risk of
      death compared with 16.6% for the others. Some 72.7% of patient who did not get
      RT had cerebellar or spinal ependymoma. Patients undergoing surgery had 16.3%
      risk of death, as compared to 23.7% among those who did not have surgery.
      CONCLUSION: Grading ependymoma may dramatically improve modeling of data. RT is
      under used for cerebellum and spinal cord ependymoma and it may be a potential
      way to improve outcome.

PMID- 24568510
TI  - Prognostic significance of desmoglein 2 and desmoglein 3 in esophageal squamous
      cell carcinoma.
AB  - OBJECTIVE: Desmogleins (DSGs) are major members among the desmosomal cadherins
      critically involved in cell-cell adhesion and the maintenance of normal tissue
      architecture in epithelia. Reports exploring links of DSG family member
      expression with cancers are few and vary. The aim of this study was to
      investigate the ratio of DSG2 and DSG3 mRNA expression in esophageal squamous
      cell carcinoma (ESCC) tissue to normal tissue (T/N ratio) and evaluate
      correlations with clinical parameters. METHODS: The mRNA expression of DSGs, as
      well as gamma-catenin and desmoplakin, was detected by real-time quantitative RT
      PCR in 85 cases of ESCC tissue specimens. RESULTS: The expression level of DSG3
      mRNA was significantly higher than that of DSG2 in ESCC specimens (p = 0.000).
      DSG3 mRNA expression highly correlated with histological grade (p = 0.009),
      whereas that of DSG2 did not significantly relate to any clinicopathologic
      parameter. Kaplan-Meier survival analysis showed that only DSG3 expression had an
      impact on the survival curve, with negative DSG3 expression indicating worse
      survival (p = 0.038). Multivariate Cox regression analysis demonstrated DSG3 to
      be an independent prognostic factor for survival. Furthermore, correlation
      analysis demonstrated the mRNA level of DSG3 to highly correlate with those of
      gamma-catenin and desmoplakin in ESCC samples (p=0.000), implying that the
      expression of desmosomal components might be regulated by the same upstream
      regulatory molecules. CONCLUSIONS: Our findings suggest that DSG3 may be involved
      in the progression of ESCC and serve as a prognostic marker, while expression of
      DSG2 cannot be used as a predictor of ESCC patient outcome.

PMID- 24568512
TI  - Survival of patients with prostate cancer in Yazd, Iran.
AB  - BACKGROUND: Prostate cancer is the second leading cause of cancer death in men
      worldwide. Several factors such as availability of screening tests, and dietary,
      other lifestyle, environmental and genetic influences contribute to worldwide
      disparities in prostate cancer incidence and mortality rates. Our aims were to
      investigate patient characteristics at the time of diagnosis, common treatment
      strategies employed and survival in an Iranian male population with prostate
      cancer. MATERIALS AND METHODS: Archives of Pathology Departments of five referral
      centers affiliated with the School of Medicine of Shahid Sadoughi University in
      Yazd province were reviewed. Paraffin-embedded blocks were reviewed by two
      independent pathologists to confirm the diagnosis. The latest modification of the
      Gleason Scoring System was adopted to determine pathological grading. Following
      pathological evaluation, patients were contacted via telephone to acquire
      information regarding their current status. RESULTS: Pathology blocks were
      available for 113 patients. However, upon phone contacts, we were unable to
      determine the survival status in 23 patients (response rate=83%). Therefore, 90
      patients were enrolled in the final analysis. The median follow-up time was 6.0
      years (ranging from 0.3 to 8.8 years). There were 30 death attributed to prostate
      cancer in the study group. Kaplan-Meier analysis revealed that patient age at the
      time of diagnosis was a significant predictor of survival. Another significant
      predictor of poorer survival was higher tumor grade. CONCLUSIONS: Our
      observations indicate that age and pathological grade can negatively affect
      survival of individuals with prostate cancer in Iran.

PMID- 24568511
TI  - Factors for postoperative gallstone occurrence in patients with gastric cancer: a
      meta-analysis.
AB  - OBJECTIVE: To evaluate risk factors for gallstones after gastrectomy. METHODS: To
      identify documents published from 1990 to 2011 the Pubmed, Cochrane Library,
      Springer Link, CBM and WanFang databases were searched and a meta-analysis was
      performed with RevMan 5.2 software for odds ratios and 95%CIs. RESULTS: Fifteen
      studies were selected for the meta-analysis. The pooled ORs [95%CIs] were 0.56
      [0.43, 0.73], (P<0.0001) for digestive tract reconstruction, 0.80 [0.54, 1.17],
      (P=0.25) for pylorus preservation, 0.33[0.15, 0.75], (P=0.008) for resection
      scope of stomach, 0.33 [0.15, 0.75], (P=0.008) for lymphadenectomy, and 0.13
      [0.05, 0.33], (P<0.0001) for vagotomy. CONCLUSIONS: Digestive tract physical
      reconstruction and vagus nerve preservation can reduce the morbidity of
      gallstones after gastrectomy. Total gastrectomy can add to the morbidity of
      galltones as does increasing the degree of lymph node dissection. There was no
      significant difference in gallstones with or without pylorus preservation.

PMID- 24568513
TI  - Locoregional spread and survival of stage IIA1 versus stage IIA2 cervical cancer.
AB  - This study was undertaken to compare surgical outcomes and survival rates of
      patients with the 2009 International Federation of Gynecology and Obstetrics
      (FIGO) stage IIA1 versus IIA2 cervical cancer treated with radical hysterectomy
      and pelvic lymphadenectomy (RHPL). Patients with stage IIA cervical cancer
      undergoing primary RHPL between January 2003 and December 2012 at Chiang Mai
      University Hospital were retrospectively reviewed. The analysis included
      clinicopathologic variables, i.e. nodal metastasis, parametrial involvement,
      positive surgical margins, deep stromal invasion (DSI)), lymph-vascular space
      invasion (LVSI), adjuvant treatment, and 5-year survival. The chi square test,
      Kaplan-Meier method and log-rank test were used for statistical analysis. During
      the study period, 133 women with stage IIA cervical cancer, 101 (75.9 %) stage
      IIA1, and 32 (24.1 %) stage IIA2 underwent RHPL. The clinicopathologic variables
      of stage IIA1 compared with stage IIA2 were as follows: nodal metastasis (38.6%
      vs 40.6%, p=0.84), parametrial involvement (10.9% vs 15.6%, p=0.47), positive
      surgical margins (31.7% vs 31.3%, p=1.0), DSI (39.6% vs 53.1%, p=0.18), LVSI
      (52.5% vs 71.9%, p=0.05) and adjuvant radiation (72.3% vs 84.4%, p=0.33). With a
      median follow-up of 60 months, the 5-year disease-free survival (84.6% vs 88.7%,
      p=0.67) and the 5-year overall survival (83.4% vs 90.0%, P=0.49) did not
      significantly differ between stage IIA1 and stage IIA2 cervical cancer. In
      conclusion, patients with stage IIA1 and stage IIA2 cervical cancer have
      comparable rates of locoregional spread and survival. The need for receiving
      adjuvant radiation was very high in both substages. The revised 2009 FIGO system
      did not demonstrate significant survival differences in stage IIA cervical cancer
      treated with radical hysterectomy. Concurrent chemoradiation should be considered
      a more suitable treatment for patients with stage IIA cervical cancer. 

PMID- 24568514
TI  - PAX1 methylation analysis by MS-HRM is useful in triage of high-grade squamous
      intraepithelial lesions.
AB  - This study is aimed to investigate the role of paired boxed gene 1 (PAX1)
      methylation analysis by methylation- sensitive high-resolution melting (MS-HRM)
      in the detection of high grade lesions in atypical squamous cells cannot exclude
      high-grade squamous intraepithelial lesion (ASC-H) and compared its performance
      with the Hybrid Capture 2 (HC2) human papillomavirus (HPV) test. In our study,
      130 cases with a diagnosis of ASC-H from the cervical cytological screening by
      Thinprep cytologic test (TCT) technique were selected for triage. Their cervical
      scrapings were collected and evaluated by using PAX1 methylation analysis (MS
      HRM) and high-risk HPV DNA test (HC2), followed by colposcopy and cervical
      biopsy. Chi-square test were used to test the differences of PAX1 methylation or
      HPV infection between groups. In the detection of CIN2+, the sensitivity,
      specificity, the PPV, NPV and the accuracy of PAX1 MS-HRM assay and high-risk HPV
      (HR-HPV) tests were respectively 80.6% vs 67.7%, 94.9% vs 54.5%, 83.3%, vs 31.8%,
      94.0% vs 84.4%, and 91.5% vs 57.7%. The PAX1 MS-HRM assay proved superior to HR
      HPV testing in the detection of high grade lesions (CIN2+) in ASC-H. This
      approach could screen out the majority of high grade lesion cases of ASC-H, and
      thus could reduce the referral rate to colposcopy. 

PMID- 24568515
TI  - Cytogenetic and genetic mutation features of de novo acute myeloid leukemia in
      elderly Chinese patients.
AB  - OBJECTIVES: The present study aimed to examine the cytogenetic and genetic
      mutation features of acute myeloid leukemia (AML) in elderly Chinese patients.
      METHODS: A retrospective analysis of cytogenetics and genetic mutations was
      performed in 113 cases (age range 50-82 years) with de novo AML. RESULTS: The
      most frequent cytogenetic abnormality was t (15;17) (q22;q21), detected in 10.0%
      (n = 9) of successfully analyzed cases, followed by t (8;21) (q22;q22) in 8.89%
      (n = 8), and complex karyotypes in 5.56% (n = 5). Those with complex karyotypes
      included 4 cases (4.44%) of monosomal karyotypes. The frequencies of NPM1, FLT3
      ITD, c-kit, and CEBPA mutations were 27.4% (31/113), 14.5% (16/110), 5.88%
      (6/102), and 23.3% (7/30), respectively. The complete remission rates of patients
      in low, intermediate, and high risk groups were 37.5%, 48.6%, and 33.3%,
      respectively (chi2 = 0.704, P = 0.703) based on risk stratification. CONCLUSION:
      Cytogenetics and genetic mutations alone may not be sufficient to evaluate the
      prognoses of elderly AML patients. The search for a novel model that would enable
      a more comprehensive evaluation of this population is therefore imperative.

PMID- 24568516
TI  - Gemcitabine and Cisplatin followed by chemo-radiation for advanced nasopharyngeal
      carcinoma.
AB  - Concurrent chemo-radiation (CRT) has been established as the standard of care for
      non-metastatic loco- regionally advanced nasopharyngeal carcinoma (NPC) but
      recently the addition of induction chemotherapy in the already established
      regimen has presented an attractive multidisciplinary approach. This
      retrospective study was carried out to evaluate the efficacy of induction
      chemotherapy (IC) followed by CRT for the management of loco-regionally advanced
      NPC. Between July 2005 and September 2010, 99 patients were treated with
      cisplatin based IC followed by CRT. Induction chemotherapy included a 2 drug
      combination; intravenous gemcitabine 1000 mg/m2 on day 1 and 8 and cisplatin 75
      mg/m2 on day 1 only. Radiotherapy (RT) was given as a phase treatment to a total
      dose of 70 Gy in 35 fractions. Concurrent cisplatin (75 mg/m2) was administered
      to all patients on days 1, 22 and 43. All patients were evaluated for tumor
      response and adverse effects after IC and 6 weeks after the completion of the
      treatment protocol. Statistical analysis was performed using SPSS version 17 and
      Kaplan Meier estimates were applied to project survival. Median follow-up
      duration was 20 months. The 5-year overall survival (OS), loco regional control
      (LRC) and relapse free survival (RFS) rates were 71%, 73% and 50%respectively.
      Acute grade 4 toxicity related to induction chemotherapy and concurrent chemo
      radiation was 4% and 2% respectively, with only 3 toxicity-related hospital
      admissions. We conclude that induction gemcitabine and cisplatin followed by
      chemo-radiation is a safe and effective regimen in management of nasopharyngeal
      carcinoma, meriting further investigation in randomized clinical trials. 

PMID- 24568517
TI  - Women's perceptions and attitudes about cervical cancer in Turkey: Kato's device
      as an alternative to the Pap smear.
AB  - AIMS: To determine the status of women's perception and attitudes about cervical
      cancer and their thoughts on Kato's self-sampling device. MATERIALS AND METHODS:
      This descriptive research was conducted between July- December 2012 with a study
      populationof married women older than 18 years. RESULTS: A total of 246 women
      volunteered, with a mean age of 34.9+/-9.22 (19-52). In the last year, 52.0% had
      been examined by a gynecologist to address a complaint or for a periodic health
      check. Of the 118 who had not had a gynecological examination, 42.4% indicated
      negligence, 26.3% stated the reason was no complaint, 14.4% feared they might
      receive bad results from the examination, and 8.5% stated that were shy or
      embarrassed. Of all of the women, 35.0% answered that they had information about
      cervical cancer, and 0.7% had heard about the HPV vaccine. No one in their
      families had received the vaccine. Of the women, 28.5% had had a Pap smear, and
      71.4% of those had normal results. Of those who had never had a Pap smear, 47.2%
      had never heard about the test; 18.8% explained the reason for not having a test
      as shyness or embarrassment with a male doctor. None of the women had heard about
      Kato's device. Once the women were informed, 73.6% expresseed interest in use;
      51.9% answered they could use it and not be embarrassed, 30.9% would use it
      because they did not have to see a doctor, and 17.1% would use it as it allows
      them to take a smear in all conditions and whenever they want. Of the women,
      60.0% thought that they could not successfully use Kato's device; 40.0% thought
      that a smear should be taken by a doctor. CONCLUSIONS: Most of the women in our
      population had never had a Pap smear and wanted to use the Kato's device.

PMID- 24568518
TI  - Whole brain radiotherapy combined with stereotactic radiotherapy versus
      stereotactic radiotherapy alone for brain metastases: a meta-analysis.
AB  - AIM: This study was to evaluate the effect of whole brain radiation (WBRT)
      combined with stereotactic radiotherapy (SRS) versus stereotactic radiotherapy
      alone for patients with brain metastases using a meta- analysis. MATERIALS AND
      METHODS: We searched PubMed, EMBASE, Cochrane Library from their inception up to
      October 2013. Randomized controlled trials involving whole brain radiation
      combined with stereotactic radiotherapy versus stereotactic radiotherapy alone
      for brain metastases were included. Statistical analyses were performed using
      RevMan5.2 software. RESULTS: Four randomized controlled trials including 903
      patients were included. The meta-analysis showed statistically significant
      lowering of the local recurrence rate (OR=0.29, 95%CI: 0.17~0.49), new brain
      metastasis rate (OR=0.45, 95%CI: 0.28~0.71) and symptomatic late neurologic
      radiation toxicity rate (OR=3.92, 95%CI: 1.37~11.20) in the combined group. No
      statistically significant difference existed in the 1-year survival rate
      (OR=0.78, 95%CI: 0.60~1.03). CONCLUSIONS: The results indicate that whole brain
      radiotherapy combined with stereotactic radiotherapy has advantages in local
      recurrence and new brain metastasis rates, but stereotactic radiotherapy alone is
      associated with better neurological function. However, as the samples included
      were not large, more high-quality, large-sample size studies are necessary for
      confirmation.

PMID- 24568519
TI  - MicroRNA-100 resensitizes resistant chondrosarcoma cells to cisplatin through
      direct targeting of mTOR.
AB  - Chondrosarcomas are malignant cartilage-forming tumors of bone which exhibit
      resistance to both chemotherapy and radiation treatment. miRNAs have been well
      demonstrated to regulate gene expression and play essential roles in a variety of
      biological processes, including proliferation, differentiation, migration, cell
      cycling and apoptosis. In this study, we obtained evidence that miR-100 acts as a
      tumor suppressor in human chondrosarcomas. Interestingly, cisplatin resistant
      chondrosarcoma cells exhibit decreased expression of miR-100 compared with
      parental cells. In addition, we identified mTOR as a direct target of miR-100.
      Overexpression of miR-100 complementary pairs to the 3' untranslated region (UTR)
      of mTOR, resulted in sensitization of cisplatin resistant cells to cisplatin.
      Moreover, recovery of the mTOR pathway by overexpression of S6K desensitized the
      chondrosarcoma cells to cisplatin, suggesting the miR-100-mediated sensitization
      to cisplatin dependent on inhibition of mTOR. In summary, the present studies
      highlight miR-100 as a tumor suppressor in chondrosarcoma contributing to anti
      chemoresistance. Overexpression of miR-100 might be exploited as a therapeutic
      strategy along with cisplatin-based combined chemotherapy for the treatment of
      clinical chondrosarcoma patients. 

PMID- 24568520
TI  - Treatment of extremely high risk and resistant gestational trophoblastic
      neoplasia patients in King Chulalongkorn Memorial Hospital.
AB  - BACKGROUND: Gestational trophoblastic neoplasia (GTN) is a spectrum of disease
      with abnormal trophoblastic proliferation. Treatment is based on FIGO stage and
      WHO risk factor scores. Patients whose score is 12 or more are considered as at
      extremely high risk with a high likelihood of resistance to first line treatment.
      Optimal therapy is therefore controversial. OBJECTIVE: This study was conducted
      in order to summarize the regimen used for extremely high risk or resistant GTN
      patients in our institution the in past 10 years. MATERIALS AND METHODS: All the
      charts of GTN patients classified as extremely high risk, recurrent or resistant
      during 1 January 2002 to 31 December 2011 were reviewed. Criteria for diagnosis
      of GTN were also assessed to confirm the diagnosis. FIGO stage and WHO risk
      prognostic score were also re-calculated to ensure the accuracy of the
      information. Patient characteristics were reviewed in the aspects of age, weight,
      height, BMI, presenting symptoms, metastatic area, lesions, FIGO stage, WHO risk
      factor score, serum hCG level, treatment regimen, adjuvant treatments, side
      effects and response to treatment, including disease free survival. RESULTS:
      Eight patients meeting the criteria of extremely high risk or resistant GTN were
      included in this review. Mean age was 33.6 years (SD= 13.5, range 17-53). Of the
      total, 3 were stage III (37.5%) and 5 were stage IV (62.5%). Mean duration from
      previous pregnancies to GTN was 17.6 months (SD 9.9). Mean serum hCG level was
      864,589 mIU/ml (SD 98,151). Presenting symptoms of the patients were various such
      as hemoptysis, abdominal pain, headache, heavy vaginal bleeding and stroke. The
      most commonly used first line chemotherapeutic regimen in our institution was the
      VAC regimen which was given to 4 of 8 patients in this study. The most common
      second line chemotherapy was EMACO. Adjuvant radiation was given to most of the
      patients who had brain metastasis. Most of the patients have to delay
      chemotherapy for 1-2 weeks due to grade 2-3 leukopenia and require G-CSF to
      rescue from neutropenia. Five form 8 patients were still survived. Mean of
      disease free survival was 20.4 months. Two patients died of the disease, while
      another one patient died from sepsis of pressure sore wound. None of surviving
      patients developed recurrence of disease after complete treatment. CONCLUSIONS:
      In extremely high risk GTN patients, main treatment is multi-agent chemotherapy.
      In our institution, we usually use VAC as a first line treatment of high risk
      GTN, but since resistance is quite common, this may not suitable for extremely
      high risk GTN patients. The most commonly used second line multi-agent
      chemotherapy in our institution is EMA-CO. Adjuvant brain radiation was
      administered to most of the patients with brain metastasis in our institution.
      The survival rate is comparable to previous reviews. Our treatment demonstrated
      differences from other institutions but the survival is comparable. The
      limitation of this review is the number of cases is small due to rarity of the
      disease. Further trials or multicenter analyses may be considered.

PMID- 24568521
TI  - Comparative study of toxic effects of anatase and rutile type nanosized titanium
      dioxide particles in vivo and in vitro.
AB  - Two types of nanosized titanium dioxide, anatase (anTiO2) and rutile (rnTiO2),
      are widely used in industry, commercial products and biosystems. TiO2 has been
      evaluated as a Group 2B carcinogen. Previous reports indicated that anTiO2 is
      less toxic than rnTiO2, however, under ultraviolet irradiation anTiO2 is more
      toxic than rnTiO2 in vitro because of differences in their crystal structures. In
      the present study, we compared the in vivo and in vitro toxic effects induced by
      anTiO2 and rnTiO2. Female SD rats were treated with 500 ?g/ml of anTiO2 or rnTiO2
      suspensions by intra-pulmonary spraying 8 times over a two week period. In the
      lung, treatment with anTiO2 or rnTiO2 increased alveolar macrophage numbers and
      levels of 8-hydroxydeoxyguanosine (8-OHdG); these increases tended to be lower in
      the anTiO2 treated group compared to the rnTiO2 treated group. Expression of
      MIP1??mRNA and protein in lung tissues treated with anTiO2 and rnTiO2 was also
      significantly up-regulated, with MIP1??mRNA and protein expression significantly
      lower in the anTiO2 group than in the rnTiO2 group. In cell culture of primary
      alveolar macrophages (PAM) treated with anTiO2 and rnTiO2, expression of
      MIP1??mRNA in the PAM and protein in the culture media was significantly higher
      than in control cultures. Similarly to the in vivo results, MIP1??mRNA and
      protein expression was significantly lower in the anTiO2 treated cultures
      compared to the rnTiO2 treated cultures. Furthermore, conditioned cell culture
      media from PAM cultures treated with anTiO2 had less effect on A549 cell
      proliferation compared to conditioned media from cultures treated with rnTiO2.
      However, no significant difference was found in the toxicological effects on cell
      viability of ultra violet irradiated anTiO2 and rnTiO2. In conclusion, our
      results indicate that anTiO2 is less potent in induction of alveolar macrophage
      infiltration, 8-OHdG and MIP1??expression in the lung, and growth stimulation of
      A549 cells in vitro than rnTiO2. 

PMID- 24568522
TI  - Bioinformatic prediction of SNPs within miRNA binding sites of inflammatory genes
      associated with gastric cancer.
AB  - Polymorphisms in miRNA binding sites have been shown to affect miRNA binding to
      target genes, resulting in differential mRNA and protein expression and
      susceptibility to common diseases. Our purpose was to predict SNPs (single
      nucleotide polymorphisms) within miRNA binding sites of inflammatory genes in
      relation to gastric cancer. A complete list of SNPs in the 3'UTR regions of all
      inflammatory genes associated with gastric cancer was obtained from Pubmed. miRNA
      target prediction databases (MirSNP, Targetscan Human 6.2, PolymiRTS 3.0,
      miRNASNP 2.0, and Patrocles) were used to predict miRNA target sites. There were
      99 SNPs with MAF>0.05 within the miRNA binding sites of 41 genes among 72
      inflammation-related genes associated with gastric cancer. NF-kappaB and JAK-STAT
      are the two most important signaling pathways. 47 SNPs of 25 genes with 95 miRNAs
      were predicted. CCL2 and IL1F5 were found to be the shared target genes of hsa
      miRNA-624-3p. Bioinformatic methods could identify a set of SNPs within miRNA
      binding sites of inflammatory genes, and provide data and direction for
      subsequent functional verification research. 

PMID- 24568524
TI  - Clinicopathological features of colon adenocarcinoma in Qazvin, Iran: a 16 year
      study.
AB  - BACKGROUND: Colorectal cancer (CRC) was the fourth most commonly diagnosed cancer
      in Iran between 2000 and 2009, with adenocarcinoma (AC) as the most common
      histological type. Demographic, topographic and histological variables are
      important in the epidemiology and biology of cancer. The aim of this study was to
      investigate clinicopathological features of colon adenocarcinomas in Qazvin,
      Iran. MATERIALS AND METHODS: With a retrospective design, patient records of two
      pathology wards from March 1997 to March 2013 were studied with regard to
      anatomical location and histological classification. A broader anatomical
      grouping was also used including distal vs proximal regions and right sided vs
      left sided tumors. Data were analyzed using T-test and chi-square test. RESULTS:
      118 (50.9%) male and 114 (49.1%) female patients were included in the study. Mean
      age was 57.3+/-14.7 years, with 29.2% under 50 years. There was no significant
      gender difference for age at diagnosis. The rectum (56%) and sigmoid colon (25%)
      were the most frequent anatomical locations. Proximal cases accounted for 18.6%
      in males and 8.8% in females (p=0.02). AC was more prevalent than other usual
      types in younger patients. The proportion of proximal cancer was 1.7% in first
      eight years of the study period vs 12.1% in the second one (p=0.005). A similar
      trend was also seen in right sided colon cancers (p=0.018). CONCLUSIONS: Young
      people are also at risk for the cancer with poor prognosis. Screening programs
      and weight loss in obese individuals can reduce incidence and complications of
      CRC.

PMID- 24568523
TI  - Neutrophil count and the inflammation-based glasgow prognostic score predict
      survival in patients with advanced gastric cancer receiving first-line
      chemotherapy.
AB  - PURPOSE: To explore the value of systemic inflammatory markers as independent
      prognostic factors and the extent these markers improve prognostic classification
      for patients with inoperable advanced or metastatic gastric cancer (GC) receiving
      palliative chemotherapy. METHODS: We studied the prognostic value of systemic
      inflammatory factors such as circulating white blood cell count and its
      components as well as that combined to form inflammation-based prognostic scores
      (Glasgow Prognostic Score (GPS), Neutrophil-Lymphocyte Ratio (NLR), Platelet
      Lymphocyte Ratio (PLR), Prognostic Index (PI) and Prognostic Nutritional Index
      (PNI)) in 384 patients with inoperable advanced or metastatic gastric cancer (GC)
      receiving first-line chemotherapy. Univariate and multivariate analyses were
      performed to examine the impact of inflammatory markers on overall survival (OS).
      RESULTS: Univariate analysis revealed that an elevated white blood cell,
      neutrophil and/or platelet count, a decreased lymphocyte count, a low serum
      albumin concentration, and high CRP concentration, as well as elevated NLR/PLR ,
      GPS, PI, PNI were significant predictors of shorter OS. Multivariate analysis
      demonstrated that only elevated neutrophil count (HR 3.696, p=0.003) and higher
      GPS (HR 1.621, p=0.01) were independent predictors of poor OS. CONCLUSION: This
      study demonstrated elevated pretreatment neutrophil count and high GPS to be
      independent predictors of shorter OS in inoperable advanced or metastatic GC
      patients treated with first-line chemotherapy. Upon validation of these data in
      independent studies, stratification of patients using these markers in future
      clinical trials is recommended.

PMID- 24568526
TI  - Asiatic acid promotes p21(WAF1/CIP1) protein stability through attenuation of
      NDR1/2 dependent phosphorylation of p21(WAF1/ CIP1) in HepG2 human hepatoma
      cells.
AB  - Previous studies have suggested anti-tumor effects of asiatic acid in some human
      cancer cell lines. This agent is reported to increase the levels of p21WAF1/CIP1
      in human breast cancer cell lines. However, the molecular mechanisms have not
      been established. Here we report that asiatic acid up-regulates p21WAF1/CIP1
      protein expression but not the level of p21WAF1/CIP1 mRNA in HepG2 human hepatoma
      cells. Furthermore, we found that the asiatic acid induced increase of
      p21WAF1/CIP1 protein was associated with decreased phosphorylation (ser-146) of
      p21WAF1/CIP1. Knockdown of NDR1/2 kinase, which directly phosphorylates
      p21WAF1/CIP1 protein at ser-146 and enhances its proteasomal degradation,
      increased the levels of p21WAF1/CIP1 protein and eliminated the regulation of
      p21WAF1/ CIP1 stability by asiatic acid. At the same time, the expression of
      NDR1/2 kinase decreased during treatment with asiatic acid in HepG2 cells.
      Moreover, asiatic acid inhibited the proliferation of HepG2 cells, this being
      attenuated by knockdown of p21WAF1/CIP1. In conclusion, we propose that asiatic
      acid inhibits the expression NDR1/2 kinase and promotes the stability of
      p21WAF1/CIP1 protein through attenuating NDR1/2 dependent phosphorylation of
      p21WAF1/CIP1 in HepG2 cells. 

PMID- 24568525
TI  - Lack of associations between Vitamin D metabolism-related gene variants and risk
      of colorectal cancer.
AB  - PURPOSE: With regard to the protective effect of vitamin D against colorectal
      cancer (CRC), we evaluated genetic variants that might influence vitamin D
      metabolism: vitamin D receptor (VDR), vitamin D binding protein (GC), vitamin D
      25-hydroxylase (CYP2R1), and vitamin D 25-hydroxy 1-alpha hydroxylase (CYP27B1).
      MATERIALS AND METHODS: A total of 657 subjects, including 303 cases with CRC and
      354 controls were enrolled in this case-control study. All 657 were genotyped for
      the four gene variants using PCR-RFLP methods. RESULTS: In this study, no
      significant difference was observed for VDR (rs2238136), GC (rs4588), CYP2R1
      (rs12794714), and CYP27B1 (rs3782130) gene variants in either genotype or allele
      frequencies between the cases with CRC and the controls and this lack of
      difference remained even after adjustment for age, BMI, sex, smoking status,
      NSAID use, and family history of CRC. Furthermore, no evidence for effect
      modification of the variants and CRC by BMI, sex, or tumor site was observed.
      CONCLUSIONS: Our findings do not support a role for VDR, GC, and CYP27B1 genes in
      CRC risk in our Iranian population. Another interesting finding, which to our
      knowledge has not been reported previously, was the lack of association with the
      CYP2R1 gene polymorphism. Nonetheless, our findings require confirmation and
      possible roles of vitamin D metabolism-related genes in carcinogenesis need to be
      further investigated.

PMID- 24568528
TI  - Comparison of cervical cell morphology using two different cytology techniques
      for early detection of pre-cancerous lesions.
AB  - Cervical cancer is an issue of foremost importance globally, specifically
      affecting the developing nations. Significant advances have taken place with
      regard to diagnosis of cervical cancer, especially with screening. Appropriate
      screening measures can thus reduce the incidence of cervical cancer. The most
      desirable screening technique should be less invasive, easy to perform, cost
      effective and cover a wide range of diagnostic icons. Manual liquid based
      cytology (MLBC) can be considered as one of the suitable technique for screening
      with the above-mentioned benefits. The aim of the current study was to compare
      two cervical screening techniques on the basis of different morphological
      parameters and staining parameters by using modified acetic acid Pap staining to
      see the possibility of reducing time economy involved in conventional Pap
      staining (CPS). The study was conducted on a total 88 cases and all were analyzed
      with both MLBC and CPS. Forty eight cases that were regarded as satisfactory on
      the basis of Bethesda system by both methods were further recruited for
      investigation. Their morphological parameters and staining quality were compared
      and scored according to a scoring system defined in the study. Quality indices
      was calculated for both staining procedures and smear techniques. 

PMID- 24568527
TI  - Development and application of telephone counseling services for care of patients
      with colorectal cancer.
AB  - BACKGROUND: The number of colorectal cancer (CRC) patients in Taiwan has
      increased in recent years; therefore, the effective dissemination of information
      related to symptom care has become especially important. Previous studies
      indicated that the physical and psychological status of cancer patients can be
      effectively improved by telephone counseling services (TCS). Thus, determining
      the most effective means of establishing a TCS to support the clinical practice
      of oncology has become a crucial goal for nursing. The purposes of this study
      were to analysis the content of the TCS for CRC and explore stratification of the
      TCS. MATERIALS AND METHODS: The study design was retrospective. A total of 850
      calls were made to CRC patients in the cancer center of Southern Taiwan during
      the period of January 2007- December 2011. A structure questionnaire was adopted
      to analysis satisfaction. RESULTS: Responses provided by the TCS included
      information regarding nutrition, side effects resulting from chemotherapy and
      pain. Moreover, 28.7% of CRC patients needed advanced treatment. More than 90%
      satisfaction with all aspects of the calls was found. CONCLUSIONS: The TCS coulkd
      be shown to provide an effective means by which to expand the reach of nursing
      care to different times, places and patients, allowing for greater cost
      efficiency and more rapid service.

PMID- 24568529
TI  - Cytotoxicity of Nigella sativa seed oil and extract against human lung cancer
      cell line.
AB  - Nigella sativa (N sativa), commonly known as black seed, has been used in
      traditional medicine to treat many diseases. The antioxidant, anti-inflammatory,
      and antibacterial activities of N sativa extracts are well known. Therefore, the
      present study was designed to investigate the anticancer activity of seed extract
      (NSE) and seed oil (NSO) of N sativa against a human lung cancer cell line. Cells
      were exposed to 0.01 to 1 mg/ml of NSE and NSO for 24 h, then percent cell
      viability was assessed by 3-(4, 5-dimethylthiazol-2yl)-2, 5-biphenyl tetrazolium
      bromide (MTT) and neutral red uptake (NRU) assays, and cellular morphology by
      phase contrast inverted microscopy. The results showed NSE and NSO significantly
      reduce the cell viability and alter the cellular morphology of A-549 cells in a
      concentration dependent manner. The percent cell viability was recorded as 75%,
      50%, and 26% at 0.25, 0.5, and 1 mg/ml of NSE by MTT assay and 73%, 48%, and 23%
      at 0.25, 0.5, and 1 mg/ml of NSE by NRU assay. Exposure to NSO concentrations of
      0.1 mg/ml and above for 24 h was also found to be cytotoxic. The decrease in cell
      viability at 0.1, 0.25, 0.5, and 1 mg/ml of NSO was recorded to be 89%, 52%, 41%,
      and 13% by MTT assay and 85%, 52%, 38%, and 11% by NRU assay, respectively. A-549
      cells exposed to 0.25, 0.5 and 1 mg/ml of NSE and NSO lost their typical
      morphology and appeared smaller in size. The data revealed that the treatment of
      seed extract (NSE) and seed oil (NSO) of Nigella sativa significantly reduce
      viability of human lung cancer cells. 

PMID- 24568530
TI  - Aberrant expression of the autocrine motility factor receptor correlates with
      poor prognosis and promotes metastasis in gastric carcinoma.
AB  - AMFR, autocrine motility factor receptor, also called gp78, is a cell surface
      cytokine receptor which has a dual role as an E3 ubiquitin ligase in endoplasmic
      reticulum-associated degradation. AMFR expression is associated with tumor
      malignancy. We here investigated the clinical significance of AMFR and its role
      in metastasis and prognosis in gastric cancer. Expression of AMFR, E-cadherin and
      N-cadherin in cancer tissues and matched adjacent normal tissues from 122 gastric
      cancer (GC) patients undergoing surgical resection was assessed by
      immunohistochemistry. Levels of these molecules in 17 cases selected randomly
      were also analysed by Western blotting. AMFR expression was significantly
      increased in gastric cancer tissues, and associated with invasion depth and lymph
      node metastasis. Kaplan-Meier analysis showed AMFR expression correlated with
      poor overall survival and an increased risk of recurrence in the GC cases. Cox
      regression analysis suggested AMFR to be an independent predictor for overall and
      recurrence-free survival. E-cadherin expression was decreased in gastric cancer
      tissues; conversely, N-cadherin was increased. Expression of AMFR negatively
      correlated with E-cadherin expression, whereas N-cadherin expression showed a
      significant positive correlation with AMFR expression. AMFR might be involved in
      the regulation of epithelial-mesenchymal transition, with aberrant expression
      correlating with a poor prognosis and promoting invasion and metastasis in GCs. 

PMID- 24568531
TI  - MACC1 expression correlates with PFKFB2 and survival in hepatocellular carcinoma.
AB  - OBJECTIVE: To validate the relationship between MACC1 and 6-phosphofructo-2
      kinase/fructose 2, 6 bisphosphatase (PFKFB2) expression as well as its
      clinicopathological features and prognostic significance in hepatocellular
      carcinoma. METHODS: By using immunohistochemistry, we investigated the MACC1 and
      PFKFB2 protein expression in 60 pairs of hepatocellular carcinoma and
      corresponding non-tumor tissues. Using the Mann-Whitney U test, the Chi-square
      test, Kaplan-Meier survival analysis, Cox proportional hazard regression analysis
      and Spearman analysis, we studied the relationship between MACC1 and PFKFB2
      protein expression and postoperative overall survival (OS) of the HCC patients.
      RESULTS: MACC1 and PFKFB2 positive staining rates were significantly higher in
      hepatocellular carcinoma than in the corresponding nontumor tissues (P=0.012 and
      0.04, respectively). The clinicopathological features evaluation revealed that
      positive expression of MACC1 was associated with a high Edmondson classification
      (P=0.007) and advanced TNM stage (P=0.027). Similar findings were evident for
      PFKFB2 expression (P=0.002 and P=0.027). MACC1 and PFKFB2 positive expression was
      associated with a lower OS rate (P=0.004 and 0.03, respectively). Kaplan-Meier
      survival and Cox proportional hazard regression analyses revealed MACC1 positive
      expression to be a prognostic factor for postoperative OS, but PFKFB was not.
      CONCLUSION: Highly expressed MACC1 and PFKFB2 protein were associated with TNM
      stage, Edmondson -Steier classification and overall survival. MACC1 may affect
      tumor metabolism partly through expression and phophorylation of PFKFB2.

PMID- 24568532
TI  - Anti-smoking initiatives and current smoking among 19,643 adolescents in South
      Asia: findings from the Global Youth Tobacco Survey.
AB  - BACKGROUND: Cigarette smoking habit usually begins in adolescence. The developing
      countries in South Asia like Pakistan, India, Bangladesh, and Nepal, where the
      largest segment of the population is comprised of adolescents, are more
      susceptible to smoking epidemic and its consequences. Therefore, it is important
      to identify the association between anti-smoking initiatives and current smoking
      status in order to design effective interventions to curtail the smoking epidemic
      in this region. METHODS: This is a secondary analysis of national data from the
      Global Youth Tobacco Survey (GYTS) conducted in Pakistan (year 2003), India (year
      2006), Bangladesh (year 2007), and Nepal (year 2007). GYTS is a school-based
      survey of students targeting adolescents of age 13-15 years. We examined the
      association of different ways of delivering anti-smoking messages with students'
      current smoking status. RESULTS: A total of 19,643 schoolchildren were included
      in this study. The prevalence of current smoking was 5.4% with male predominance.
      No exposure to school teachings, family discussions regarding smoking hazards,
      and anti-smoking media messages was significantly associated with current smoking
      among male students. Participants who were deprived of family discussion
      regarding smoking hazards (girls: odds ratio (OR) 1.56, 95% confidence interval
      (CI) 0.84-2.89, p value 0.152; boys: OR 1.37, 95% CI 1.04-1.80, p value 0.025),
      those who had not seen media messages (girls: OR 2.89, 95% CI 1.58-5.28, p value
      <0.001; boys: OR 1.32, 95% CI 0.91-1.88, p value 0.134), and those who were not
      taught the harmful effects of smoking at school (girls: OR 2.00, 95% CI 0.95
      4.21, p value 0.066; boys: OR 1.89, 95% CI 1.44-2.48, p value <0.001) had higher
      odds of being current smokers after multivariate adjustment. CONCLUSION: School
      going adolescents in South Asia (Pakistan, India, Nepal, and Bangladesh) who were
      not exposed to anti-tobacco media messages or were not taught about the harmful
      effects in school or at home had higher odds of being current smokers than their
      counterparts.

PMID- 24568535
TI  - Thermally robust Au99(SPh)42 nanoclusters for chemoselective hydrogenation of
      nitrobenzaldehyde derivatives in water.
AB  - We report the synthesis and catalytic application of thermally robust gold
      nanoclusters formulated as Au99(SPh)42. The formula was determined by
      electrospray ionization and matrix-assisted laser desorption ionization mass
      spectrometry in conjunction with thermogravimetric analysis. The optical spectrum
      of Au99(SPh)42 nanoclusters shows absorption peaks at ~920 nm (1.35 eV), 730 nm
      (1.70 eV), 600 nm (2.07 eV), 490 nm (2.53 eV), and 400 nm (3.1 eV) in contrast to
      conventional gold nanoparticles, which exhibit a plasmon resonance band at 520 nm
      (for spherical particles). The ceria-supported Au99(SPh)42 nanoclusters were
      utilized as a catalyst for chemoselective hydrogenation of nitrobenzaldehyde to
      nitrobenzyl alcohol in water using H2 gas as the hydrogen source. The selective
      hydrogenation of the aldehyde group catalyzed by nanoclusters is a surprise
      because conventional nanogold catalysts instead give rise to the product
      resulting from reduction of the nitro group. The Au99(SPh)42/CeO2 catalyst gives
      high catalytic activity for a range of nitrobenzaldehyde derivatives and also
      shows excellent recyclability due to its thermal robustness. We further tested
      the size-dependent catalytic performance of Au25(SPh)18 and Au36(SPh)24
      nanoclusters, and on the basis of their crystal structures we propose a molecular
      adsorption site for nitrobenzaldehyde. The nanocluster material is expected to
      find wide application in catalytic reactions.

PMID- 24568534
TI  - Examining the effects of perceived social support on momentary mood and symptom
      reports in asthma and arthritis patients.
AB  - OBJECTIVE: Social support has been linked to beneficial effects on health
      directly (main effect) and as a buffer to stress. Most research, however, has
      examined these relationships using global and retrospective assessments of health
      and stress, which may be subject to recall biases. This study used ambulatory
      ecological momentary assessment (EMA) methods to test the main and stress
      buffering effects of social support on the daily health and well-being of asthma
      and rheumatoid arthritis (RA) patients. DESIGN: Community volunteers with asthma
      (n = 97) or RA (n = 31) responded to EMA prompts five times daily for one week.
      MAIN OUTCOMES: Baseline perceived social support was obtained, and then,
      participants reported mood, stress and symptoms using EMA. Multilevel mixed
      modelling examined whether social support predicted mood and symptoms directly or
      via stress-reducing effects. RESULTS: Supporting a main effect, more perceived
      social support predicted decreased negative mood and stress severity. Supporting
      a stress-buffering effect, more perceived social support resulted in fewer
      reported symptoms when stress was present. CONCLUSION: Results suggest perceived
      social support directly relates to better ambulatory status and dynamically
      buffers individuals against the negative effects of stressors, and highlight the
      importance of studying social support across different temporal and contextual
      levels.

PMID- 24568533
TI  - Yield and complications of frame-based and frameless stereotactic brain biopsy-
      the value of intra-operative histological analysis.
AB  - OBJECTIVES: Image-guided brain biopsy is an established method to obtain
      histopathological diagnosis and guide management for cerebral lesions. The study
      aimed to establish negative biopsy and symptomatic haemorrhage rates at a single
      centre, and to assess the influence of factors such as lesion location, final
      pathology and the use of intra-operative smears. METHODS: A retrospective
      analysis of all frame-based and frameless stereotactic biopsies carried out over
      57 months from July 2006 to March 2011. RESULTS: A total of 351 biopsies were
      undertaken, 256 frame-based (73%) and 95 frameless (27%). Mean age was 57 years
      (range 18-87). Negative biopsy rate was 5.1%. There was a significantly greater
      negative biopsy rate in deep brain biopsies (p = 0.011) and in the cerebellum (p
      < 0.001). Intra-operative smear significantly reduced negative biopsy rates from
      11.1% to 3.7% (p = 0.011). If repeat smear was requested, yet not provided, then
      the negative biopsy rate was 57.1% (p = 0.0085). The overall symptomatic
      haemorrhage rate was 3.7%. There was a significant increase in haemorrhage rate
      in deep versus superficial biopsies (p = 0.023) and a significantly greater
      haemorrhage rate in lymphoma biopsies (p = 0.015). There was no significant
      increase in haemorrhage rate in high-grade compared with low-grade tumour
      biopsies. Mortality rates at 7 and 30 days post-operatively were 0.6% and 1.7%,
      respectively, with mortality after 7 days unrelated to biopsy. CONCLUSION: We
      advocate intra-operative histopathological analysis to decrease negative biopsy
      rates and advise increased caution when undertaking biopsies of deep lesions or
      suspected lymphoma cases due to the potentially increased risk of haemorrhage.

PMID- 24568536
TI  - Comparison of TiO2 and ZnO solar cells sensitized with an indoline dye: time
      resolved laser spectroscopy studies of partial charge separation processes.
AB  - Time-resolved laser spectroscopy techniques in the time range from femtoseconds
      to seconds were applied to investigate the charge separation processes in
      complete dye-sensitized solar cells (DSC) made with iodide/iodine liquid
      electrolyte and indoline dye D149 interacting with TiO2 or ZnO nanoparticles. The
      aim of the studies was to explain the differences in the photocurrents of the
      cells (3-4 times higher for TiO2 than for ZnO ones). Electrochemical impedance
      spectroscopy and nanosecond flash photolysis studies revealed that the better
      performance of TiO2 samples is not due to the charge collection and dye
      regeneration processes. Femtosecond transient absorption results indicated that
      after first 100 ps the number of photoinduced electrons in the semiconductor is 3
      times higher for TiO2 than for ZnO solar cells. Picosecond emission studies
      showed that the lifetime of the D149 excited state is about 3 times longer for
      ZnO than for TiO2 samples. Therefore, the results indicate that lower performance
      of ZnO solar cells is likely due to slower electron injection. The studies show
      how to correlate the laser spectroscopy methodology with global parameters of the
      solar cells and should help in better understanding of the behavior of
      alternative materials for porous electrodes for DSC and related devices. 

PMID- 24568538
TI  - Chemoselective deprotonative lithiation of azobenzenes: reactions and mechanisms.
AB  - Whereas standard strong bases (n-BuLi, s-BuLi/TMEDA, n-BuLi/t-BuOK, TMPMgCl.LiCl,
      and LDA) reduce the N?N bond of the parent azobenzene (Y = H), aromatic H->Li
      permutation occurs with LTMP when a suitable director of lithiation (Y = OMe,
      CONEt2, F) is present in the benzene residue of the azo compound. The method
      allows direct access to new substituted azobenzenes. 

PMID- 24568539
TI  - Comparison of laparoendoscopic single-site hysterectomies: laparoscopic
      hysterectomy with some vaginal component versus laparoscopically assisted vaginal
      hysterectomy.
AB  - BACKGROUND: To compare the clinical results of two types of laparoendoscopic
      single-site surgery (LESS) laparoscopic hysterectomy (LH): LH with some vaginal
      component [LH(a)] versus laparoscopically assisted vaginal hysterectomy (LAVH).
      SUBJECTS AND METHODS: This is a retrospective comparative study. A single surgeon
      performed 50 LESS-LAVH procedures consecutively between March 2009 and October
      2009 and 50 LESS-LH(a) procedures consecutively between January 2011 and July
      2011. RESULTS: Most LESS-LH(a)s/LAVH procedures were successful. Of 50 LESS-LH(a)
      procedures, 2 were converted to LESS-LAVH. Of 50 LESS-LAVHs, 1 required
      additional ports. The LESS-LH(a) group had a shorter operative time and less
      postoperative pain compared with the LESS-LAVH group. Operative complications
      were not significantly different between the groups. CONCLUSIONS: LESS-LH(a) and
      LESS-LAVH are both feasible and safe methods, with similar surgical outcomes. In
      terms of operative time and postoperative pain, LESS-LH(a) is superior to LESS
      LAVH.

PMID- 24568541
TI  - Exploration forays in juvenile European hares (Lepus europaeus): dispersal
      preludes or hunting-induced troubles?
AB  - BACKGROUND: Movements of animals have important consequences, at both the
      individual and population levels. Due to its important implications in the
      evolutionary dynamics of populations, dispersal is one of the most studied types
      of movement. In contrast, non-permanent extra home-range movements are often paid
      less attention. However, these movements may occur in response to important
      biological processes such as mating or predation avoidance. In addition, these
      forays are often preludes to permanent dispersal, because they may help
      individuals gain cues about their surroundings prior to settlement in a new
      place.In the European hare, exploration forays occur predominantly in juveniles,
      the time at which most hares disperse. In France, the timing of dispersal also
      overlaps with the hare hunting period. However, the determinants of such
      behaviour have not yet been studied. Herein, we investigate whether these non
      permanent explorations are dispersal attempts/preludes or, in contrast, whether
      they are triggered by other factors such as disturbances related to hunting.
      RESULTS: Contrary to natal dispersal, we did not find strong male-bias in the
      propensity to engage in explorations. Exploration forays occurred less in
      juveniles than in adults and later in the season than natal dispersal. This was
      the case both for philopatric movements and for movements occurring after
      dispersal and settlement. These movements were also more likely to occur during
      the hare hunting period and the mating season. CONCLUSIONS: We suggest that
      explorations in hares are triggered by factors other than dispersal and that
      hares may respond to hunting disturbances. Overall, we emphasize the need to
      account for human-related predation risk as a factor driving space-use in
      harvested species.

PMID- 24568542
TI  - Immediate development of post-varicocelectomy hydrocele: a case report and review
      of the literature.
AB  - INTRODUCTION: Hydrocele development is the most common complication after
      varicocele repair. The beginning of this kind of hydrocele is variable. The
      shortest reported onset is one week. In the present report we describe an unusual
      immediate onset of hydrocele formation following varicocele repair. This
      represents the first report of a harsh hydrocele onset in the literature. CASE
      PRESENTATION: A 29-year-old Caucasian male noticed the development of a big
      hydrocele just a few hours after inguinal varicocelectomy. The hydrocele remained
      stable in size throughout 12 years until a hydrocelectomy was done. CONCLUSION:
      Mass ligation and division of the spermatic cord structures during varicocele
      surgery should be avoided. Instead, lymphatic sparing is highly recommended.
      Differentiation between testicular edema and hydrocele should be confirmed as
      early as possible to assure the patient properly. This case study highlights the
      importance of our knowledge about the surgical anatomy of the spermatic cord
      structures. It definitely advances our understanding of a post-varicocelectomy
      hydrocele etiology and development. It is an original case report of interest to
      andrologists, urologists and general surgeons.

PMID- 24568543
TI  - Propranolol as first-line treatment in orbital infantile haemangiomas: a case
      series.
AB  - PURPOSE: To highlight the importance of Magnetic Resonance Imaging (MRI) and the
      use of propranolol as both a final diagnostic tool and adequate treatment for
      orbital Infantile Haemangiomas (IHs). METHODS: A retrospective study was
      conducted using a case series of 5 infants diagnosed with orbital IH. All
      patients presented with progressive unilateral proptosis and were at high risk of
      developing amblyopia, some had combined swelling of the eyelid, impaired eye
      movements or exposure keratopathy. Propranolol was administered in an initial
      dose of 0.6 mg/kg/day orally divided in three daily doses and increased in 4 days
      to 2.7 mg/kg/day. MRI was performed in all children. RESULTS: Striking MR
      characteristics of an IH lesion were seen in each of our 5 cases, including the
      presence of flow voids, high contrast enhancement, hypo-intense T1W signal, iso-
      to hyper intense T2W signal, and lobulated appearance. All patients showed a
      quick clinical response to treatment, resulting in significant reduction in
      tumour size within a range of 1-3 weeks and almost complete regression of the
      lesion at the end of the treatment schedule. CONCLUSIONS: Our study adds another
      5 cases to the growing body of reports confirming the efficacy and safety - under
      controlled circumstances - of propranolol therapy in orbital IH management, in
      which we highlight the use of propranolol as both a final diagnostic tool and as
      an adequate treatment.

PMID- 24568540
TI  - Prediction of outcome in patients with suspected acute ischaemic stroke with CT
      perfusion and CT angiography: the Dutch acute stroke trial (DUST) study protocol.
AB  - BACKGROUND: Prediction of clinical outcome in the acute stage of ischaemic stroke
      can be difficult when based on patient characteristics, clinical findings and on
      non-contrast CT. CT perfusion and CT angiography may provide additional
      prognostic information and guide treatment in the early stage. We present the
      study protocol of the Dutch acute Stroke Trial (DUST). The DUST aims to assess
      the prognostic value of CT perfusion and CT angiography in predicting stroke
      outcome, in addition to patient characteristics and non-contrast CT. For this
      purpose, individualised prediction models for clinical outcome after stroke based
      on the best predictors from patient characteristics and CT imaging will be
      developed and validated. METHODS/DESIGN: The DUST is a prospective multi-centre
      cohort study in 1500 patients with suspected acute ischaemic stroke. All patients
      undergo non-contrast CT, CT perfusion and CT angiography within 9 hours after
      onset of the neurological deficits, and, if possible, follow-up imaging after 3
      days. The primary outcome is a dichotomised score on the modified Rankin Scale,
      assessed at 90 days. A score of 0-2 represents good outcome, and a score of 3-6
      represents poor outcome. Three logistic regression models will be developed,
      including patient characteristics and non-contrast CT (model A), with addition of
      CT angiography (model B), and CT perfusion parameters (model C). Model derivation
      will be performed in 60% of the study population, and model validation in the
      remaining 40% of the patients. Additional prognostic value of the models will be
      determined with the area under the curve (AUC) from the receiver operating
      characteristic (ROC) curve, calibration plots, assessment of goodness-of-fit, and
      likelihood ratio tests. DISCUSSION: This study will provide insight in the added
      prognostic value of CTP and CTA parameters in outcome prediction of acute stroke
      patients. The prediction models that will be developed in this study may help
      guide future treatment decisions in the acute stage of ischaemic stroke.

PMID- 24568544
TI  - Nucleation of polyaniline nano-/macrotubes from anilinium composed micelles.
AB  - A mechanistic study on the nucleation of polyaniline nanotubes (PANI-NT) through
      template-free method is explored by in situ solution-state (1)H NMR experiments
      via a careful analysis of the spectral evolution of the major species in the
      course of the reaction. Before polymerization, aniline and salicylic acid have
      assembled into loosely packed micelles due to electrostatic interactions and the
      proton exchange reaction between aniline and anilinium. A three-stage
      polymerization with a formation, accumulation of aniline dimers, as well as a
      generation of phenazine-like oligomers is observed, which can be attributed to
      the monomer transformation from neutral aniline molecules to anilinium cations
      and the significantly lowered pH in the reaction. Strong pi-pi stacking
      interactions from the phenazine-like oligomers facilitate the intermolecular
      aggregation which initiates the formation of PANI-NT. At first, such aggregates,
      locating at the outermost layer of anilinium composed micelles, shield in situ
      formed protons from releasing into the aqueous bulk but into the micelle instead.
      Due to the continuously increased charge in the micelle, a sphere-to-rod
      structural transition occurs which leads the oligomer aggregates to be sheathed
      at the exterior of the rod. Further consumption of anilinium in the micelle
      leaves the internal cavity while the fusion between the micelles elongates the
      length of the tubes. Our work demonstrates that (i) loosely packed anilinium
      composed micelles, highly mobile monomers within the micelle, and efficient
      blockage of the proton-releasing to the aqueous bulk are three key factors for
      the generation of tubular structures; and (ii) dynamic NMR line shape analysis
      provides a new perspective for resolving the formation profile of nanostructured
      polymers. 

PMID- 24568546
TI  - Dendritic cell lectin-targeting sentinel-like unimolecular glycoconjugates to
      release an anti-HIV drug.
AB  - A series of cyclodextrin-based glycoconjugates, including glycoclusters and star
      glycopolymers, were synthesized via combination of CuAAC Huisgen coupling and
      copper-mediated living radical polymerization. These glycoconjugates showed high
      affinity binding to the human transmembrane lectin DC-SIGN and act as inhibitors
      to prevent the binding of HIV envelope protein gp120 to DC-SIGN at nanomolar
      concentrations. The star block glycopolymers showed high loading capacity of
      hydrophobic anticancer and anti-HIV drugs, indicating promising applications in
      HIV-therapeutic and smart drug delivery. 

PMID- 24568545
TI  - Recombinant adenovirus expressing the haemagglutinin of Peste des petits
      ruminants virus (PPRV) protects goats against challenge with pathogenic virus; a
      DIVA vaccine for PPR.
AB  - Peste des petits ruminants virus (PPRV) is a morbillivirus that can cause severe
      disease in sheep and goats, characterised by pyrexia, pneumo-enteritis, and
      gastritis. The socio-economic burden of the disease is increasing in
      underdeveloped countries, with poor livestock keepers being affected the most.
      Current vaccines consist of cell-culture attenuated strains of PPRV, which induce
      a similar antibody profile to that induced by natural infection. Generation of a
      vaccine that enables differentiation of infected from vaccinated animals (DIVA)
      would benefit PPR control and eradication programmes, particularly in the later
      stages of an eradication campaign and for countries where the disease is not
      endemic. In order to create a vaccine that would enable infected animals to be
      distinguished from vaccinated ones (DIVA vaccine), we have evaluated the
      immunogenicity of recombinant fowlpox (FP) and replication-defective recombinant
      human adenovirus 5 (Ad), expressing PPRV F and H proteins, in goats. The Ad
      constructs induced higher levels of virus-specific and neutralising antibodies,
      and primed greater numbers of CD8+ T cells than the FP-vectored vaccines.
      Importantly, a single dose of Ad-H, with or without the addition of Ad expressing
      ovine granulocyte macrophage colony-stimulating factor and/or ovine interleukin
      2, not only induced strong antibody and cell-mediated immunity but also
      completely protected goats against challenge with virulent PPRV, 4 months after
      vaccination. Replication-defective Ad-H therefore offers the possibility of an
      effective DIVA vaccine.

PMID- 24568547
TI  - rhPDGF-BB via ERK pathway osteogenesis and adipogenesis balancing in ADSCs for
      critical-sized calvarial defect repair.
AB  - Adipose-derived stem cells (ADSCs) with the capacity of differentiating into
      osteo-like cells have been widely investigated for bone tissue engineering as a
      novel seed cell source. Recombinant human platelet-derived growth factor (rhPDGF
      BB) is a clinically proven growth factor with the potential of promoting cell
      proliferation and osteogenic differentiation during the bone regeneration
      process. In this study, we investigated the effects of rhPDGF-BB on the
      proliferation and osteogenic and adipogenic differentiation of rat ADSCs and
      explored whether the extracellular signal-related kinase (ERK) signaling pathway
      might be involved. We found that rhPDGF-BB significantly enhanced ADSCs
      proliferation and osteogenic differentiation, as detected by MTT, real-time
      polymerase chain reaction (PCR), ALP activity assays, and calcium deposition in
      vitro, in concert with ERK pathway activation. In contrast, the adipogenesis of
      ADSCs, as detected by real-time PCR and Oil Red O staining, was suppressed in the
      presence of rhPDGF-BB. Furthermore, with the supplement of the ERK inhibitor
      PD98059, cell proliferation and osteogenesis were reduced; as expected,
      adipogenesis was enhanced. Subsequently, for the first time, we evaluated the
      effect of ADSCs associated with rhPDGF-BB on bone regeneration in a critical
      sized rat calvarial defect model with silk scaffold as a carrier. Micro-computed
      tomography and histological analyses exhibited dramatically more new bone
      formation and trabecular number in the Silk/PDGF/ADSC group. These data indicated
      that rhPDGF-BB promoted cell proliferation and osteogenic differentiation and
      suppressed adipogenic differentiation in vitro via ERK pathway and that ADSCs
      associated with rhPDGF-BB could be a promising tissue-engineered construct for
      craniofacial bone regeneration in vivo. 

PMID- 24568549
TI  - Can trehalose prevent neurodegeneration? Insights from experimental studies.
AB  - Inappropriate protein aggregation is a key mechanism in the pathogenesis of
      several neurodegenerative disorders. One of the main strategies by which cells
      deal with abnormal protein aggregates is autophagy, a degradation pathway for
      intracellular aggregate-prone proteins. Trehalose, a non-reducing disaccharide
      which has been utilized extensively in the food industry, has been recently
      demonstrated to have a number of unique properties that point to its potential
      utility in preventing neurodegeneration. First, trehalose may act as a potent
      stabilizer of proteins and is able to preserve protein structural integrity.
      Second, it is a chaperone and reduces aggregation of pathologically misfolded
      proteins. Third, it improves the clearance of the mutant proteins which act as
      autophagy substrates when aberrant protein deposition occurs. Notably, trehalose
      is an mTOR-independent inducer of autophagy, and in animal models of
      neurodegenerative disorders including Alzheimer's disease, Parkinson's disease,
      and Huntington's disease, has been shown to decrease the levels of toxic protein
      aggregates, increase autophagy, and improve clinical symptoms and survival. In
      summary, mounting experimental evidence suggests that trehalose may prevent
      neurodegenerative disorders by stabilizing proteins and promoting autophagy.
      Because of the low toxicity profile that allows for administration for extended
      periods, human studies of trehalose in preventing neurodegeneration are
      warranted. 

PMID- 24568548
TI  - Adenovirus vector-induced CD8+ T effector memory cell differentiation and
      recirculation, but not proliferation, are important for protective immunity
      against experimental Trypanosoma cruzi Infection.
AB  - Heterologous prime-boost vaccination using plasmid DNA followed by replication
      defective adenovirus vector generates a large number of specific CD8+ T effector
      memory (TEM) cells that provide long-term immunity against a variety of
      pathogens. In the present study, we initially characterized the frequency,
      phenotype, and function of these T cells in vaccinated mice that were subjected
      to infectious challenge with the human protozoan parasite Trypanosoma cruzi. We
      observed that the frequency of the specific CD8+ T cells in the spleens of the
      vaccinated mice increased after challenge. Specific TEM cells differentiated into
      cells with a KLRG1(High) CD27(Low) CD43(Low) CD183(Low)T-bet(High) Eomes(Low)
      phenotype and capable to produce simultaneously the antiparasitic mediators
      IFNgamma and TNF. Using the gzmBCreERT2/ROSA26EYFP transgenic mouse line, in
      which the cells that express Granzyme B after immunization, are indelibly labeled
      with enhanced yellow fluorescent protein, we confirmed that CD8+ T cells present
      after challenge were indeed TEM cells that had been induced by vaccination.
      Subsequently, we observed that the in vivo increase in the frequency of the
      specific CD8+ T cells was not because of an anamnestic immune response. Most
      importantly, after challenge, the increase in the frequency of specific cells and
      the protective immunity they mediate were insensitive to treatment with the
      cytostatic toxic agent hydroxyurea. We have previously described that the
      administration of the drug FTY720, which reduces lymphocyte recirculation,
      severely impairs protective immunity, and our evidence supports the model that
      when large amounts of antigen-experienced CD8+ TEM cells are present after
      heterologous prime-boost vaccination, differentiation, and recirculation, rather
      than proliferation, are key for the resultant protective immunity.

PMID- 24568550
TI  - Proteomic analysis of bovine blastocoel fluid and blastocyst cells.
AB  - The understanding of the early mammalian development is a prerequisite for the
      advancement of in vitro fertilization and improvement of derivation and culturing
      of embryonic stem cells. While, whole genome transcriptomic analysis on bovine
      blastocysts has identified genes active in early development, little information
      is available about the protein complement of early embryos. Modern, sensitive
      proteomic technology (nano HPLC tandem mass spectrometry) allowed us to describe
      the proteome of the scarce blastocoel fluid and cell material of expanded bovine
      blastocysts isolated by micromanipulation. From two independent replicates, 23
      proteins were identified in the blastocoel fluid while 803 proteins were
      identified in the remaining cell material. The proteins were grouped into
      categories according to their gene ontology (GO) terms by which proteins involved
      in cell differentiation, cell proliferation, development, and reproduction could
      be derived. Proteins classified in these categories could be candidates for
      further functional studies to understand pluripotency and early mammalian
      development.

PMID- 24568551
TI  - The ESR1 gene in unexplained recurrent spontaneous abortion.
AB  - Recurrent spontaneous abortion (RSA) is a health problem that affects nearly 1%
      of fertile couples. However, the underlying etiology and mechanism(s) remain
      elusive. The aim of this study was to investigate estrogen receptor (ESR) 1 gene
      polymorphisms for risk association of unexplained recurrent spontaneous abortion
      (URSA) in the Chinese Han population. The entire coding region of the ESR1 gene
      was sequenced from 129 URSA patients and 183 healthy controls. There was a
      significant difference between the G allele and GG genotype distributions, of the
      ESR1 gene (XbaI) polymorphism, between the URSA and the control groups (chi(2) =
      14.93, df = 1, p < 0.001, OR = 2.01 95% CI: 1.41-2.88 by allele; chi(2) = 12.24,
      df = 2, p = 0.002 by genotype). The PvuII polymorphism, C allele frequency was
      higher in RSA than in controls (41.9% vs. 34.7%, respectively). Women carrying C
      G haplotype were associated with an increased risk of URSA in this population
      (permutation test p value = 0.016, OR = 1.76 95% CI: 1.19-2.59). Estrogen
      receptor 1 gene PvuII and XbaI polymorphisms were associated with URSA in a
      Chinese Han population. However, independent replication of these associations
      are necessary to assure veracity.

PMID- 24568552
TI  - Measurement of perceived functions of non-suicidal self-injury for Chinese
      adolescents.
AB  - Due to the lack of validated assessment tools for motives of non-suicidal self
      injury behaviors in the Chinese contexts, this study aims to evaluate the
      psychometric properties of the Chinese version of the Functional Assessment of
      Self-Mutilation (C-FASM). A total of 345 secondary school students (mean age =
      11.41 years), who reported non-suicidal self-injury in the past year, voluntarily
      participated in the questionnaire survey. Confirmatory factor analysis results
      supported a second-order model of 4 motivational factors. The overall scale
      scores had significant correlations with depression, anxiety, impulsiveness, self
      esteem, social support, and suicidal ideation. The internal consistency of the
      scale was also satisfactory. The C-FASM is a valid and reliable instrument for
      assessing non-suicidal self-injury among nonclinical Chinese adolescents. 

PMID- 24568553
TI  - Clinical value of hematologic test in predicting tumor response to neoadjuvant
      chemotherapy with esophageal squamous cell carcinoma.
AB  - BACKGROUND: To investigate the relationship between hematologic test results and
      the predictive effect of regression of esophageal cancer after neoadjuvant
      chemotherapy (NACT), we analyzed pre-NACT hematologic data and their relationship
      to tumor regression. METHODS: Thirty-eight consecutive patients with locally
      advanced squamous cell esophageal carcinoma who had undergone two cycles of
      paclitaxel/carboplatin NACT were enrolled. On the day prior to the first cycle of
      chemotherapy, hematologic tests, including routine blood test and biochemical
      examinations, were recorded. All patients were confirmed to have no history of
      hepatitis. Surgical resection was performed when clinical restaging showed
      effective regression. Histopathological examination was routinely performed to
      evaluate the postoperative effects of chemotherapy. RESULTS: After two cycles of
      NACT, tumor imaging evaluation showed that 27 of the 38 patients had CR and PR,
      including 25 patients who underwent radical esophagectomies. Six patients had
      stable disease and five patients had progressive disease. According to the
      hematologic test results before NACT, patients with higher white blood cell
      counts, lymphocyte percentages, mononuclear cell counts, neutrophilic granulocyte
      counts, and eosinophilic granulocyte counts and lower alanine aminotransferase
      (ALT) level had a significantly greater opportunity for an effective response.
      CONCLUSION: Basal host immunologic function and hepatic function are associated
      with tumor response to NACT in patients with esophageal cancer. These parameters
      may have a certain predictive efficacy on NACT for esophageal squamous cell
      carcinoma.

PMID- 24568555
TI  - Commercialization of biopharmaceutical knowledge in Iran; challenges and
      solutions.
AB  - BACKGROUND: The objective of this study was to investigate the application of the
      university research findings or commercialization of the biopharmaceutical
      knowledge in Iran and determine the challenges and propose some solutions.
      RESULTS: A qualitative study including 19 in-depth interviews with experts was
      performed in 2011 and early 2012. National Innovation System (NIS) model was
      employed as the study design. Thematic method was applied for the analysis. The
      results demonstrate that policy making, regulations and management development
      are considered as fundamental reasons for current commercialization practice
      pattern. It is suggested to establish foundation for higher level documents that
      would involve relating bodies and provide them operational guidelines for the
      implementation of commercialization incentives. CONCLUSIONS: Policy, regulations
      and management as the most influential issue should be considered for successful
      commercialization. The present study, for the first time, attempts to disclose
      the importance of evidence input for measures in order to facilitate the
      commercialization process by the authorities in Iran. Overall, the NIS model
      should be considered and utilized as one of the effective solutions for
      commercialization.

PMID- 24568554
TI  - Conformational dynamics of a Y-family DNA polymerase during substrate binding and
      catalysis as revealed by interdomain Forster resonance energy transfer.
AB  - Numerous kinetic, structural, and theoretical studies have established that DNA
      polymerases adjust their domain structures to enclose nucleotides in their active
      sites and then rearrange critical active site residues and substrates for
      catalysis, with the latter conformational change acting to kinetically limit the
      correct nucleotide incorporation rate. Additionally, structural studies have
      revealed a large conformational change between the apoprotein and the DNA-protein
      binary state for Y-family DNA polymerases. In previous studies [Xu, C., Maxwell,
      B. A., Brown, J. A., Zhang, L., and Suo, Z. (2009) PLoS Biol. 7, e1000225], a
      real-time Forster resonance energy transfer (FRET) method was developed to
      monitor the global conformational transitions of DNA polymerase IV from
      Sulfolobus solfataricus (Dpo4), a prototype Y-family enzyme, during nucleotide
      binding and incorporation by measuring changes in distance between locations on
      the enzyme and the DNA substrate. To elucidate further details of the
      conformational transitions of Dpo4 during substrate binding and catalysis, in
      this study, the real-time FRET technique was used to monitor changes in distance
      between various pairs of locations in the protein itself. In addition to
      providing new insight into the conformational changes as revealed in previous
      studies, the results here show that the previously described conformational
      change between the apo and DNA-bound states of Dpo4 occurs in a mechanistic step
      distinct from initial formation or dissociation of the binary complex of Dpo4 and
      DNA. 

PMID- 24568556
TI  - Van Wyk and Grumbach syndrome: an unusual form of precocious puberty.
AB  - An 8-year-old girl presented with precocious menstruation and growth delay.
      Laboratory data revealed hypothyroidism and an X-ray of the wrist showed a
      delayed bone age. The Van Wyk and Grumbach syndrome (VWGS) was diagnosed and
      thyroid replacement was started with resolution of the symptoms. The association
      of precocious puberty and/or polycystic ovaries, delayed bone age and
      hypothyroidism is known as the Van Wyk and Grumbach syndrome. Clinically this
      syndrome is a diagnostic challenge because hypothyroidism usually leads to
      pubertal and growth delay, whereas in case of VWGS hypothyroidism it leads to
      growth delay and precocious puberty. The pathophysiology of VWGS is not yet
      clear, but the most accepted theory states that the high concentrations of TSH
      are sufficient to cause activation of the FSH receptor and produce gonadal
      enlargement. Thyroid replacement therapy results in a resolution of all signs and
      symptoms. For this reason, conservative management of the ovarian masses is
      advocated. Our case is unique as this girl did not have breast development or
      multicystic ovaries (as the other cases in the literature). This may be due to an
      early recognition and relatively low TSH levels in comparison to other cases.

PMID- 24568557
TI  - Efficacy of IVF following conservative management of endometrial cancer.
AB  - Five cases of conservative management of early stage uterine carcinoma were
      reported. All patients successfully underwent in vitro fertilization (IVF). Role
      of conservative treatment, IVF and prophylactic surgery followed competition of
      parity was discussed.

PMID- 24568558
TI  - Optimization of dental status improves long-term outcome after alveolar bone
      grafting in unilateral cleft lip and palate.
AB  - Objective : To evaluate the importance of dental status for long-term outcome
      after alveolar bone grafting in patients with unilateral cleft lip and palate.
      Design : Retrospective longitudinal study. Setting : Cleft lip and palate
      craniofacial center, Uppsala University Hospital, Sweden. Patients : A total of
      67 consecutive patients with unilateral complete cleft lip and palate.
      Interventions : Secondary alveolar bone grafting, prior to the eruption of the
      permanent canine, was performed at the average age of 10.0 years (range, 8.5 to
      12.0 years). Main Outcome Measures : Alveolar bone height was evaluated with the
      modified Bergland index at 1 and 10 years after surgery. Results : Of the
      patients, 97% had modified Bergland index grade I and the remaining 3% had
      modified Bergland index grade II at 1 year after surgery. At 10 years' follow-up,
      43% showed modified Bergland index grade I; 55%, modified Bergland index grade
      II; and 2% (one patient), modified Bergland index grade III. The degree of dental
      anomalies in the cleft area, such as enamel hypoplasia, incisor rotation, incisor
      inclination, canine inclination, and oral hygiene registered preoperatively, all
      correlated negatively to the modified Bergland index at 10 years after surgery.
      Enamel hypoplasia (rho = 0.70195, P < .0001), followed by canine inclination (rho
      = 0.55429, P < .0001), showed the strongest correlation to reduced bone height in
      the cleft area. Conclusions : In patients with unilateral cleft lip and palate,
      excellent results from secondary alveolar bone grafting in terms of bone height
      in the alveolar cleft tend to decrease with time. This seems to be correlated
      with factors that might to some extent be treated preoperatively through adequate
      planning and execution of the orthodontic treatment. 

PMID- 24568560
TI  - Acquired defects in CFTR-dependent beta-adrenergic sweat secretion in chronic
      obstructive pulmonary disease.
AB  - RATIONALE: Smoking-induced chronic obstructive pulmonary disease (COPD) is
      associated with acquired systemic cystic fibrosis transmembrane conductance
      regulator (CFTR) dysfunction. Recently, sweat evaporimetry has been shown to
      efficiently measure beta-adrenergic sweat rate and specifically quantify CFTR
      function in the secretory coil of the sweat gland. OBJECTIVES: To evaluate the
      presence and severity of systemic CFTR dysfunction in smoking-related lung
      disease using sweat evaporimetry to determine CFTR-dependent sweat rate. METHODS:
      We recruited a cohort of patients consisting of healthy never smokers (N = 18),
      healthy smokers (12), COPD smokers (25), and COPD former smokers (12) and
      measured beta-adrenergic sweat secretion rate with evaporative water loss, sweat
      chloride, and clinical data (spirometry and symptom questionnaires). MEASUREMENTS
      AND MAIN RESULTS: beta-adrenergic sweat rate was reduced in COPD smokers (41.9 +/
      3.4, P < 0.05, +/- SEM) and COPD former smokers (39.0 +/- 5.4, P < 0.05)
      compared to healthy controls (53.6 +/- 3.4). Similarly, sweat chloride was
      significantly greater in COPD smokers (32.8 +/- 3.3, P < 0.01) and COPD former
      smokers (37.8 +/- 6.0, P < 0.01) vs. healthy controls (19.1 +/- 2.5). Univariate
      analysis revealed a significant association between beta-adrenergic sweat rate
      and female gender (beta = 0.26), age (-0.28), FEV1% (0.35), dyspnea (-0.3), and
      history of smoking (-0.27; each P < 0.05). Stepwise multivariate regression
      included gender (0.39) and COPD (-0.43) in the final model (R()2 = 0.266, P <
      0.0001). CONCLUSIONS: beta-adrenergic sweat rate was significantly reduced in
      COPD patients, regardless of smoking status, reflecting acquired CFTR dysfunction
      and abnormal gland secretion in the skin that can persist despite smoking
      cessation. beta-adrenergic sweat rate and sweat chloride are associated with COPD
      severity and clinical symptoms, supporting the hypothesis that CFTR decrements
      have a causative role in COPD pathogenesis.

PMID- 24568562
TI  - Motivated empathy: the mechanics of the empathic gaze.
AB  - Successful human social interactions frequently rely on appropriate interpersonal
      empathy and eye contact. Here, we report a previously unseen relationship between
      trait empathy and eye-gaze patterns to affective facial features in video-based
      stimuli. Fifty-nine healthy adult participants had their eyes tracked while
      watching a three-minute long "sad" and "emotionally neutral" video. The video
      stimuli portrayed the head and shoulders of the same actor recounting a fictional
      personal event. Analyses revealed that the greater participants' trait emotional
      empathy, the more they fixated on the eye-region of the actor, regardless of the
      emotional valence of the video stimuli. Our findings provide the first empirical
      evidence of a relationship between empathic capacity and eye-gaze pattern to the
      most affective facial region (eyes). 

PMID- 24568561
TI  - Effects of carbon dioxide pneumoperitoneum on the inflammatory response and
      bacterial translocation in intraabdominal infection.
AB  - BACKGROUND: This study evaluated the effect of CO2 pneumoperitoneum on
      intraabdominal infection and bacterial translocation in intraabdominal infection.
      MATERIALS AND METHODS: Escherichia coli and Bacteroides fragilis were injected
      separately into the abdominal cavities of 30 New Zealand white rabbits to
      establish two animal models of intraabdominal infection. Each model was divided
      into a laparotomy group, a pneumoperitoneum group, and a control group. Before
      and 1, 2, 4, and 7 days after surgery, blood and peritoneal fluids were obtained
      to determine bacterial culture and serum interleukin-6, tumor necrosis factor
      alpha, and C-reactive protein levels by enzyme-linked immunosorbent assay. The
      total number of white blood cells (WBCs) was measured. Seven days after surgery,
      the animals were sacrificed and dissected, and liver, kidney, and spleen tissues
      were obtained for bacterial culture. RESULTS: In the two bacterial models,
      incidence rates of bacteremia were higher in the laparotomy and pneumoperitoneum
      groups than in the control group. However, there were no significant differences
      between the laparotomy and pneumoperitoneum groups. Visceral bacterial
      translocation was detected in each group with no significant difference among the
      three groups. The change of inflammatory factors in the E. coli group and the B.
      fragilis group was nearly the same: the inflammatory factor levels and WBC counts
      in the laparotomy group were significantly higher than in the pneumoperitoneum
      group. The inflammatory factor levels and WBC counts in the pneumoperitoneum
      group increased slowly and were restored to normal quickly. CONCLUSIONS: In the
      intraabdominal infection animal model of the pneumoperitoneum group, the
      inflammatory response was weaker and the immune function was less affected and
      restored to normal more quickly than in the laparotomy group. The incidence rate
      of visceral bacterial translocation was not higher than that in the laparotomy
      group.

PMID- 24568563
TI  - Reengineering the optical absorption cross-section of photosynthetic reaction
      centers.
AB  - Engineered cysteine residues near the primary electron donor (P) of the reaction
      center from the purple photosynthetic bacterium Rhodobacter sphaeroides were
      covalently conjugated to each of several dye molecules in order to explore the
      geometric design and spectral requirements for energy transfer between an
      artificial antenna system and the reaction center. An average of 2.5 fluorescent
      dye molecules were attached at specific locations near P. The enhanced absorbance
      cross-section afforded by conjugation of Alexa Fluor 660 dyes resulted in a 2.2
      fold increase in the formation of reaction center charge-separated state upon
      intensity-limited excitation at 650 nm. The effective increase in absorbance
      cross-section resulting from the conjugation of two other dyes, Alexa Fluor 647
      and Alexa Fluor 750, was also investigated. The key parameters that dictate the
      efficiency of dye-to-reaction center energy transfer and subsequent charge
      separation were examined using both steady-state and time-resolved fluorescence
      spectroscopy as well as transient absorbance spectroscopy techniques. An
      understanding of these parameters is an important first step toward developing
      more complex model light-harvesting systems integrated with reaction centers. 

PMID- 24568559
TI  - Multitarget drug discovery for tuberculosis and other infectious diseases.
AB  - We report the discovery of a series of new drug leads that have potent activity
      against Mycobacterium tuberculosis as well as against other bacteria, fungi, and
      a malaria parasite. The compounds are analogues of the new tuberculosis (TB) drug
      SQ109 (1), which has been reported to act by inhibiting a transporter called
      MmpL3, involved in cell wall biosynthesis. We show that 1 and the new compounds
      also target enzymes involved in menaquinone biosynthesis and electron transport,
      inhibiting respiration and ATP biosynthesis, and are uncouplers, collapsing the
      pH gradient and membrane potential used to power transporters. The result of such
      multitarget inhibition is potent inhibition of TB cell growth, as well as very
      low rates of spontaneous drug resistance. Several targets are absent in humans
      but are present in other bacteria, as well as in malaria parasites, whose growth
      is also inhibited. 

PMID- 24568564
TI  - Implantation of autologous adipose-derived cells reconstructs functional urethral
      sphincters in rabbit cryoinjured urethra.
AB  - We investigated the ability of autologous adipose-derived cells injected into
      cryoinjured rabbit urethras to improve urinary continence and explored the
      possible mechanisms by which it occurred. Adipose tissue was harvested from the
      perivesical region of nine 10-week-old female New Zealand White rabbits and
      cultured for 7 days. Immediately after harvesting the tissue, we injured the
      internal urethral orifice by spraying liquid nitrogen for 20 s. The cultured
      cells expressed the mesenchymal cell marker STRO1, but not muscle cell markers
      myoglobin or smooth muscle actin (SMA). Just before implantation, the adipose
      derived cells were labeled with the PKH26 fluorescent cell linker. Autologous
      2.0*10(6) adipose-derived cells (five rabbits) or a cell-free control solution
      (four rabbits) was injected around the cryoinjured urethras at 7 days after
      injury. Fourteen days later, the leak point pressure (LPP) was measured, and the
      urethras were harvested for immunohistochemical analyses. At 14 days after
      implantation, LPP of the cell-implanted group was significantly higher compared
      with the cell-free control group (p<0.05). In immunohistochemical examination,
      the reconstructed skeletal and smooth muscle areas in the cell-implanted regions
      were significantly more developed than those in controls (p<0.01). Implanted
      PKH26-labeled adipose-derived cells were immunohistochemically positive for
      myoglobin, SMA, and Pax7 antibodies, which are markers for skeletal muscles,
      smooth muscles, and myoblast progenitor cells, respectively. In addition, these
      implanted cells were positive for the nerve cell markers, tubulin beta3, S100,
      and the vascular endothelial cell marker, von Willebrand factor. Furthermore,
      some of the implanted cells were positive for the transforming growth factor
      beta1, nerve growth factor, and vascular endothelial growth factor. In
      conclusion, implantation of autologous adipose-derived cells into the cryoinjured
      rabbit urethras promoted the recovery of urethral function by myogenic
      differentiation, neuroregeneration, and neoangiogenesis of the implanted cells
      and/or the surrounding tissues as well as by bulking effects. Thus, treatment of
      human radical prostatectomy-related stress urinary incontinence by adipose
      derived cell implantation could have significant therapeutic effects. 

PMID- 24568565
TI  - The development of a model of training in child psychiatry for non-physician
      clinicians in Ethiopia.
AB  - BACKGROUND: The lack of trained mental health professionals has been an important
      barrier to establishing mental health services in low income countries. The
      purpose of this paper is to describe the development and implementation of child
      psychiatry training within a graduate program in mental health for non-physician
      clinicians in Ethiopia. METHODS: The existing needs for competent practitioners
      in child psychiatry were identified through discussions with psychiatrists
      working in Ethiopia as well as with relevant departments within the Federal
      Ministry of Health Ethiopia (FMOHE). As part of a curriculum for a two year
      Master of Science (MSC) in Mental Health program for non-physician clinicians,
      child psychiatry training was designed and implemented by Jimma University with
      the involvement of experts from Addis Ababa University (AAU), Ethiopia, and
      Ludwig-Maximillian's University, (LMU), Germany. Graduates gave feedback after
      completing the course. The World Health Organization's (WHO) Mental Health Gap
      Action Program (mhGAP) intervention guide (IG) adapted for Ethiopian context was
      used as the main training material. RESULTS: A two-week child psychiatry course
      and a four week child psychiatry clinical internship were successfully
      implemented during the first and the second years of the MSC program
      respectively. During the two week psychiatry course, trainees learned to observe
      the behavior and to assess the mental status of children at different ages who
      had a variety of mental health conditions. Assessment of the trainees' clinical
      skills was done by the instructors at the end of the child psychiatry course as
      well as during the subsequent four week clinical internship. The trainees
      generally rated the course to be 'very good' to 'excellent'. Many of the
      graduates have become faculty at the various universities in Ethiopia.
      CONCLUSION: Child psychiatry training for non-physician mental health specialist
      trainees was developed and successfully implemented through collaboration with
      other universities. The model of institutional collaboration in training mental
      health professionals in the context of limited resources provides a useful guide
      for other low income countries where there is scarcity of psychiatrists.

PMID- 24568566
TI  - Effects of gender and motivations on perceptions of nonmedical use of
      prescription stimulants.
AB  - OBJECTIVE: This study examined the impact on college students' perceptions of
      nonmedical use of prescription stimulants (NMUPS) of motivation for use and
      gender. PARTICIPANTS: Participants were college students (N=695) from 2
      universities in different regions of the United States. METHODS: Participants
      read a vignette describing a college student who used a prescription stimulant
      for a nonmedical purpose and rated their perception of that individual using a
      semantic differential. A 2 (participant gender) by 2 (gender of the individual
      described in the vignette) by 3 (motive for use: get high, study, lose weight)
      design was used. RESULTS: The male who used a stimulant to study was rated
      significantly less negatively than if he used the stimulant to get high. NMUPS as
      a study aid was viewed the least negatively overall. CONCLUSIONS: Findings
      suggest that gender does not, whereas motivation for use does, impact students'
      perceptions of NMUPS.

PMID- 24568567
TI  - Cytotoxic and HIV-1 enzyme inhibitory activities of Red Sea marine organisms.
AB  - BACKGROUND: Cancer and HIV/AIDS are two of the greatest public health and
      humanitarian challenges facing the world today. Infection with HIV not only
      weakens the immune system leading to AIDS and increasing the risk of
      opportunistic infections, but also increases the risk of several types of cancer.
      The enormous biodiversity of marine habitats is mirrored by the molecular
      diversity of secondary metabolites found in marine animals, plants and microbes
      which is why this work was designed to assess the anti-HIV and cytotoxic
      activities of some marine organisms of the Red Sea. METHODS: The lipophilic
      fractions of methanolic extracts of thirteen marine organisms collected from the
      Red Sea (Egypt) were screened for cytotoxicity against two human cancer cell
      lines; leukaemia (U937) and cervical cancer (HeLa) cells. African green monkey
      kidney cells (Vero) were used as normal non-malignant control cells. The extracts
      were also tested for their inhibitory activity against HIV-1 enzymes, reverse
      transcriptase (RT) and protease (PR). RESULTS: Cytotoxicity results showed strong
      activity of the Cnidarian Litophyton arboreum against U-937 (IC50; 6.5 MUg/ml +/
      2.3) with a selectivity index (SI) of 6.45, while the Cnidarian Sarcophyton
      trochliophorum showed strong activity against HeLa cells (IC50; 5.2 MUg/ml +/
      1.2) with an SI of 2.09. Other species showed moderate to weak cytotoxicity
      against both cell lines. Two extracts showed potent inhibitory activity against
      HIV-1 protease; these were the Cnidarian jelly fish Cassiopia andromeda (IC50;
      0.84 MUg/ml +/-0.05) and the red algae Galaxura filamentosa (2.6 MUg/ml +/-1.29).
      It is interesting to note that the most active extracts against HIV-1 PR, C.
      andromeda and G. filamentosa showed no cytotoxicity in the three cell lines at
      the highest concentration tested (100 MUg/ml). CONCLUSION: The strong
      cytotoxicity of the soft corals L. arboreum and S. trochliophorum as well as the
      anti-PR activity of the jelly fish C. andromeda and the red algae G. filamentosa
      suggests the medicinal potential of crude extracts of these marine organisms.

PMID- 24568570
TI  - Evaluation of hydrogen-bond acceptors for redox-switchable resorcin[4]arene
      cavitands.
AB  - Various H-bond acceptor groups were evaluated for their propensity to induce
      conformational switching between the kite and vase forms of diquinone
      diquinoxaline resorcin[4]arene cavitands upon redox interconversion. The H-bond
      acceptors were placed on the quinoxaline walls with the purpose of stabilizing
      the vase form only in the reduced hydroquinone state of the cavitand by forming H
      bonds with the hydroquinone OH groups. Design guidelines for successful acceptors
      were derived. The carboxamide acceptor was shown to be the best candidate. Based
      on this moiety, a redox-switchable triptycene-based basket that can completely
      sterically encapsulate a guest in its closed vase conformation was prepared. The
      basket binds small molecule guests with association constants of up to 10(4) M(
      1) in mesitylene-d12 and exhibits slow guest exchange kinetics with a half-life
      for guest release in the order of 10(4) s. 

PMID- 24568569
TI  - Chronodisruption increases cardiovascular risk in zebrafish via reduced clearance
      of senescent erythrocytes.
AB  - The circadian clock and the hypoxic signaling pathway play critical roles in
      physiological homeostasis as well as in pathogenesis. The bi-directionality of
      the interaction between both pathways has been shown on physiological and only
      recently also on molecular level. But the consequences of a disturbed circadian
      rhythm for the hypoxic response and the cardiovascular system have never been
      addressed in any organism. Here we show that the hypoxic response of animals
      subjected to chronodisruption is reduced by approximately 30%, as reflected by
      decreased expression levels of hypoxia inducible factor 1 and its down-stream
      target genes erythropoietin, responsible for the generation of red blood cells
      (RBC) and vascular endothelial growth factor, which is essential for proper
      vascularization. Beside malformations of their vascular beds, chronodisrupted
      animals surprisingly revealed elevated numbers of senescent erythrocytes under
      normoxic conditions, due to a reduced clearance rate via apoptosis. Over-aged
      erythrocytes in turn are characterized by decreased oxygen transport capacities
      and an increased tendency for aggregation, explaining the higher mortality of
      chronodisrupted animals observed in our study. The present study shows for the
      first time that chronodisruption strongly interferes with the hypoxic signalling
      cascade, increasing the cardiovascular risk in zebrafish due to elevated
      proportions of senescent erythrocytes. The results might shed new light on the
      etiology of the increased cardiovascular risk observed among shiftworkers. 

PMID- 24568572
TI  - Context in the development of executive functions in children.
AB  - Assessments of and interventions for executive functions have occupied a central
      role for neuropsychologists working with children with acquired brain injuries
      during the past three decades. More recently, awareness has grown about the role
      that executive functions play for all children and the significant impact they
      have on behavior and performance in home, school, and community settings. This
      article posits that demonstration of these functions in a real-world context is
      the standard by which assessment and intervention strategies should be judged. I
      then propose that contextually based interventions offer the best probability for
      meeting this standard. Support for this position is provided by the educational
      and behavioral literature on learning and transfer and by the neuroscience
      literature on pattern recognition and embodied cognition.

PMID- 24568571
TI  - Routine administration of Anti-D: the ethical case for offering pregnant women
      fetal RHD genotyping and a review of policy and practice.
AB  - BACKGROUND: Since its introduction in the 1960s Anti-D immunoglobulin (Anti-D Ig)
      has been highly successful in reducing the incidence of haemolytic disease of the
      fetus and newborn (HDFN) and achieving improvements to maternal and fetal health.
      It has protected women from other invasive interventions during pregnancy and
      prevented deaths and damage amongst newborns and is a technology which has been
      adopted worldwide. Currently about one third of pregnant women with the blood
      group Rhesus D (RhD) negative in the UK (approximately 40,000 women per year in
      England and Wales), receive antenatal Anti-D Ig in pregnancy when they do not
      require it because they are carrying a RhD negative fetus. Since 1997, a test
      using cell free fetal DNA (cffDNA) in maternal blood has been developed to
      identify the genotype of the fetus and can be used to predict the fetal RhD blood
      group. DISCUSSION: This paper considers whether it is ethically acceptable to
      continue administering antenatal Anti-D Ig to all RhD negative women when fetal
      RHD genotyping using maternal blood could identify those women who do not need
      this product. SUMMARY: The antenatal administration of Anti-D Ig to a third of
      RhD negative pregnant women who carry a RhD negative fetus and therefore do not
      need it raises important ethical issues. If fetal RHD genotyping using maternal
      blood was offered to all RhD negative pregnant women it would assist them to make
      an informed choice about whether or not to have antenatal Anti-D Ig.

PMID- 24568573
TI  - Mining images in biomedical publications: Detection and analysis of gel diagrams.
AB  - Authors of biomedical publications use gel images to report experimental results
      such as protein-protein interactions or protein expressions under different
      conditions. Gel images offer a concise way to communicate such findings, not all
      of which need to be explicitly discussed in the article text. This fact together
      with the abundance of gel images and their shared common patterns makes them
      prime candidates for automated image mining and parsing. We introduce an approach
      for the detection of gel images, and present a workflow to analyze them. We are
      able to detect gel segments and panels at high accuracy, and present preliminary
      results for the identification of gene names in these images. While we cannot
      provide a complete solution at this point, we present evidence that this kind of
      image mining is feasible. 

PMID- 24568574
TI  - Comparing methodologies for imputing ethnicity in an urban ophthalmology clinic.
AB  - PURPOSE: To compare methodologies for imputing ethnicity in an urban
      ophthalmology clinic. METHODS: Using data from 19,165 patients with self-reported
      ethnicity, surname, and home address, we compared the accuracy of three
      methodologies for imputing ethnicity: (1) a surname method based on tabulation
      from the 2000 US Census; (2) a geocoding method based on tract data from the 2010
      US Census; and (3) a combined surname geocoding method using Bayes' theorem.
      RESULTS: The combined surname geocoding model had the highest accuracy of the
      three methodologies, imputing black ethnicity with a sensitivity of 84% and
      positive predictive value (PPV) of 94%, white ethnicity with a sensitivity of 92%
      and PPV of 82%, Hispanic ethnicity with a sensitivity of 77% and PPV of 71%, and
      Asian ethnicity with a sensitivity of 83% and PPV of 79%. Overall agreement of
      imputed and self-reported ethnicity was fair for the surname method (kappa 0.23),
      moderate for the geocoding method (kappa 0.58), and strong for the combined
      method (kappa 0.76). CONCLUSION: A methodology combining surname analysis and
      Census tract data using Bayes' theorem to determine ethnicity is superior to
      other methods tested and is ideally suited for research purposes of clinical and
      administrative data.

PMID- 24568568
TI  - Mutations in RSPH1 cause primary ciliary dyskinesia with a unique clinical and
      ciliary phenotype.
AB  - RATIONALE: Primary ciliary dyskinesia (PCD) is a genetically heterogeneous
      recessive disorder of motile cilia, but the genetic cause is not defined for all
      patients with PCD. OBJECTIVES: To identify disease-causing mutations in novel
      genes, we performed exome sequencing, follow-up characterization, mutation
      scanning, and genotype-phenotype studies in patients with PCD. METHODS: Whole
      exome sequencing was performed using NimbleGen capture and Illumina HiSeq
      sequencing. Sanger-based sequencing was used for mutation scanning, validation,
      and segregation analysis. MEASUREMENTS AND MAIN RESULTS: We performed exome
      sequencing on an affected sib-pair with normal ultrastructure in more than 85% of
      cilia. A homozygous splice-site mutation was detected in RSPH1 in both siblings;
      parents were carriers. Screening RSPH1 in 413 unrelated probands, including 325
      with PCD and 88 with idiopathic bronchiectasis, revealed biallelic loss-of
      function mutations in nine additional probands. Five affected siblings of
      probands in RSPH1 families harbored the familial mutations. The 16 individuals
      with RSPH1 mutations had some features of PCD; however, nasal nitric oxide levels
      were higher than in patients with PCD with other gene mutations (98.3 vs. 20.7
      nl/min; P < 0.0003). Additionally, individuals with RSPH1 mutations had a lower
      prevalence (8 of 16) of neonatal respiratory distress, and later onset of daily
      wet cough than typical for PCD, and better lung function (FEV1), compared with 75
      age- and sex-matched PCD cases (73.0 vs. 61.8, FEV1 % predicted; P = 0.043).
      Cilia from individuals with RSPH1 mutations had normal beat frequency (6.1 +/- Hz
      at 25 degrees C), but an abnormal, circular beat pattern. CONCLUSIONS: The milder
      clinical disease and higher nasal nitric oxide in individuals with biallelic
      mutations in RSPH1 provides evidence of a unique genotype-phenotype relationship
      in PCD, and suggests that mutations in RSPH1 may be associated with residual
      ciliary function.

PMID- 24568575
TI  - Factors affecting operating time in laparoscopic anterior resection of rectal
      cancer.
AB  - BACKGROUND: The objective of this study is to clarify the relationship between
      demographic and surgical factors and operating time, and thus operative
      difficulty, in patients undergoing laparoscopic anterior resection for mid-low
      rectal cancer, since different studies have derived different results. METHODS:
      The records of patients with mid-low rectal cancer who underwent laparoscopic
      anterior resection were retrospectively studied. Demographic data, tumor
      characteristics, and pelvimetry measurements were collected and analyzed with
      respect to operating time, using correlation coefficient analysis, principle
      component analysis, and linear regression. RESULTS: A total of 14 patients (10
      males, 4 females; 65.50 +/- 7.12 years of age) were included. Demographic and
      tumor characteristics not correlated with operating time. Body mass index (BMI)
      (P = 0.001); interacetabular distance (IA) (P = 0.001); anatomical transverse
      distance (IP) (P = 0.008); interischial distance (IS) (P = 0.002); intertuberous
      distance (IT) (P = 0.005); distance between the coccyx and symphysis (CoSy) (P =
      0.013); and the angle of the lower border of the symphysis pubis, upper border of
      symphysis pubis, and sacral promontory (angle 5) (P = 0.004) were significantly
      associated with operating time. The equation was:operatingtime=0.653 * BMI+0.818
      * angle5-0.404 * IA-0.380 * IP-0.512 * IS-0.405*IT-0.570 * CoSy+330.8.
      CONCLUSIONS: Transverse diameters of the pelvis, BMI, angle 5, and CoSy played
      the most important role in affecting operating time. The equation can be a very
      useful tool for preoperative assessment.

PMID- 24568577
TI  - Toxicological evaluation of aerosols of a tobacco extract formulation and
      nicotine formulation in acute and short-term inhalation studies.
AB  - A formulation of tobacco extract containing 4% nicotine (TE) and similar nicotine
      formulation containing vehicle and 4% nicotine (NF) were evaluated using animal
      inhalation assays. Two 4-h inhalation exposures at 1 and 2 mg/L aerosol exposure
      concentrations, respectively, of the tobacco extract with 4% nicotine formulation
      showed that the LC50 was greater than 2 mg/L, the maximum concentration tested.
      All inhalation exposures were conducted using the capillary aerosol generator
      (CAG). Increasing aerosol TPM concentrations (0, 10, 50, 200, 1000 mg/m(3) TE and
      0, 50, 200, 500, 1000 mg/m(3) NF) were generated via the CAG and used to expose
      groups of male and female rats for 4-h per day for 14 days. In life monitors for
      potential effects included clinical observations, weekly body weights and food
      consumption. Post mortem evaluations included gross tissue findings, hematology,
      clinical chemistry, serum plasma and nicotine levels, absolute and normalized
      organ and tissue weights, and histopathology of target organs. Treatment-related
      changes were observed in body weights, hematology, clinical chemistry, organ
      weights and histopathological findings for TE at the 200 and 1000 mg/m(3)
      exposure levels, and in the 500 and 1000 mg/m(3) exposure groups for NF. Under
      the conditions of these studies, the no-observed-adverse-effect level in the rat
      was approximately 50 mg/m(3) for the TE aerosol-exposed groups, and approximately
      200 mg/m(3) in the NF aerosol-exposed groups.

PMID- 24568576
TI  - Integrated nanoplasmonic sensing for cellular functional immunoanalysis using
      human blood.
AB  - Localized surface plasmon resonance (LSPR) nanoplasmonic effects allow for label
      free, real-time detection of biomolecule binding events on a nanostructured
      metallic surface with simple optics and sensing tunability. Despite numerous
      reports on LSPR bionanosensing in the past, no study thus far has applied the
      technique for a cytokine secretion assay using clinically relevant immune cells
      from human blood. Cytokine secretion assays, a technique to quantify
      intercellular-signaling proteins secreted by blood immune cells, allow
      determination of the functional response of the donor's immune cells, thus
      providing valuable information about the immune status of the donor. However,
      implementation of LSPR bionanosensing in cellular functional immunoanalysis based
      on a cytokine secretion assay poses major challenges primarily owing to its
      limited sensitivity and a lack of sufficient sample handling capability. In this
      paper, we have developed a label-free LSPR biosensing technique to detect cell
      secreted tumor necrosis factor (TNF)-alpha cytokines in clinical blood samples.
      Our approach integrates LSPR bionanosensors in an optofluidic platform that
      permits trapping and stimulation of target immune cells in a microfluidic chamber
      with optical access for subsequent cytokine detection. The on-chip spatial
      confinement of the cells is the key to rapidly increasing a cytokine
      concentration high enough for detection by the LSPR setup, thereby allowing the
      assay time and sample volume to be significantly reduced. We have successfully
      applied this approach first to THP-1 cells and then later to CD45 cells isolated
      directly from human blood. Our LSPR optofluidics device allows for detection of
      TNF-alpha secreted from cells as few as 1000, which translates into a nearly 100
      times decrease in sample volume than conventional cytokine secretion assay
      techniques require. We achieved cellular functional immunoanalysis with a minimal
      blood sample volume (3 MUL) and a total assay time 3 times shorter than that of
      the conventional enzyme-linked immunosorbent assay (ELISA). 

PMID- 24568578
TI  - In vivo genotoxicity evaluation of lung cells from Fischer 344 rats following 28
      days of inhalation exposure to MWCNTs, plus 28 days and 90 days post-exposure.
AB  - Despite their useful physico-chemical properties, carbon nanotubes (CNTs)
      continue to cause concern over occupational and human health due to their
      structural similarity to asbestos. Thus, to evaluate the toxic and genotoxic
      effect of multi-wall carbon nanotubes (MWCNTs) on lung cells in vivo, eight-week
      old rats were divided into four groups (each group = 25 animals), a fresh air
      control (0 mg/m(3)), low (0.17 mg/m(3)), middle (0.49 mg/m(3)), and high (0.96
      mg/m(3)) dose group, and exposed to MWCNTs via nose-only inhalation 6 h per day,
      5 days per week for 28 days. The count median length and geometric standard
      deviation for the MWCNTs determined by TEM were 330.18 and 1.72 nm, respectively,
      and the MWCNT diameters ranged from 10 to 15 nm. Lung cells were isolated from
      five male and five female rats in each group on day 0, day 28 (only from males)
      and day 90 following the 28-day exposure. The total number of animals used was 15
      male and 10 female rats for each concentration group. To determine the
      genotoxicity of the MWCNTs, a single cell gel electrophoresis assay (Comet assay)
      was conducted on the rat lung cells. As a result of the exposure, the olive tail
      moments were found to be significantly higher (p < 0.05) in the male and female
      rats from all the exposed groups when compared with the fresh air control. In
      addition, the high-dose exposed male and middle and high-dose exposed female rats
      retained DNA damage, even 90 days post-exposure (p < 0.05). To investigate the
      mode of genotoxicity, the intracellular reactive oxygen species (ROS) levels and
      inflammatory cytokine levels (TNF-alpha, TGF- beta, IL-1, IL-2, IL-4, IL-5, IL
      10, IL-12 and IFN-gamma) were also measured. For the male rats, the H2O2 levels
      were significantly higher in the middle (0 days post-exposure) and high- (0 days
      and 28 days post-exposure) dose groups (p < 0.05). Conversely, the female rats
      showed no changes in the H2O2 levels. The inflammatory cytokine levels in the
      bronchoalveolar lavage (BAL) fluid did not show any statistically significant
      difference. Interestingly, the short-length MWCNTs deposited in the lung cells
      were persistent at 90 days post-exposure. Thus, exposing lung cells to MWCNTs
      with a short tube length may induce genotoxicity.

PMID- 24568579
TI  - Plasma paraoxonase and arylesterase activities in smokers and smokeless tobacco
      users as Maras powder.
AB  - CONTEXT: Maras powder (MP), a different type of smokeless tobacco (ST) prepared
      from a tobacco called Nicotiana rustica Linn, is widely used in the Southern
      Turkey. Smoking and ST cause oxidative stress (OS) in the human body. Paraoxonase
      (PON) and arylesterase (ARE) are antioxidant enzymes. OBJECTIVE: To investigate
      the effects of MP on activities of PON, ARE, and malondialdehyde (MDA) levels in
      plasma and to compare these parameters in smokers and MP users (MPU). MATERIALS
      AND METHODS: The study consisted of smokers, MPU, and control group (CG) neither
      smoking nor using MP healthy subjects. PON and ARE activities were measured
      spectrophotometrically using paraoxon and phenylacetate substrates, respectively.
      RESULTS: PON and ARE activities were decreased whereas MDA levels were increased
      in tobacco groups compared to the CG. The differences of ARE and MDA values
      between the tobacco groups and CG were found statistically significant (p <
      0.01). But no significant differences were detected between the groups in the
      activity of PON (p > 0.05). However, the lowest activities of the enzymes were
      obtained in MPU. CONCLUSION: Our results can help to evaluate harmful effects of
      cigarette and ST as MP. These effects can be attributed to increased OS.
      Increased plasma MDA levels and decreased ARE activities may be important in
      assessing oxidant/antioxidant imbalance in MPU as well as smokers. Also, using of
      MP has harmful effects at least cigarette smoking.

PMID- 24568580
TI  - Potential mechanisms of neurobehavioral disturbances in mice caused by sub
      chronic exposure to low-dose VOCs.
AB  - To investigate effects of neurobehavioral disturbances in mice caused by sub
      chronic exposure to low-dose volatile organic compounds (VOCs) and the possible
      mechanism for these effects, 60 male Kunming mice were exposed in 5 similar
      static chambers, 0 (control) and 4 different doses of VOCs mixture (G1-4) for
      consecutively 90 d at 2 h/d. The concentrations of VOCs mixture were as follows:
      formaldehyde, benzene, toluene, and xylene 0.05 + 0.05 + 0.10 + 0.10 mg/m(3),
      0.10 + 0.11 + 0.20 + 0.20 mg/m(3), 0.50 + 0.55 + 1.00 + 1.00 mg/m(3), 1.00 +1.10
      + 2.00 + 2.00 mg/m(3), respectively, which corresponded to 1/2, 1, 5, and 10
      times of indoor air quality standard in China. Morris water maze (MWM) and Grip
      strength (GS) test were performed in the last 7 weeks. One day following VOCs
      exposure, oxidative stress markers, neurotransmitters, and cholinergic system
      enzymes in brain were examined. In addition, the expressions of N-methyl-d
      aspartate (NMDA) receptor in hippocampus were determined. VOCs exposure induced
      behavioral impairment of mice in MWM and GS test. The levels of reactive oxygen
      species (ROS), malondialdehyde (MDA) and glutamic acid (Glu) were significantly
      increased, while the acetylcholinesterase (AChE), choline acetyltransferase
      (ChAT) and acetylcholine (ACh) levels, and the expression of NMDA receptor were
      significantly decreased in VOCs exposed groups. Results showed that sub-chronic
      exposure to low-dose VOCs induced damage on physique and motor function, as well
      as impairment on learning and memory capacity of mice. Oxidative damage, abnormal
      metabolism of neurotransmitters and cholinergic system enzymes, and the
      alternation of NMDA receptor expression may be the possible mechanism for VOCs
      induced neurotoxicity.

PMID- 24568581
TI  - Integrating water exclusion theory into beta contacts to predict binding free
      energy changes and binding hot spots.
AB  - BACKGROUND: Binding free energy and binding hot spots at protein-protein
      interfaces are two important research areas for understanding protein
      interactions. Computational methods have been developed previously for accurate
      prediction of binding free energy change upon mutation for interfacial residues.
      However, a large number of interrupted and unimportant atomic contacts are used
      in the training phase which caused accuracy loss. RESULTS: This work proposes a
      new method, betaACVASA, to predict the change of binding free energy after
      alanine mutations. betaACVASA integrates accessible surface area (ASA) and our
      newly defined beta contacts together into an atomic contact vector (ACV). A beta
      contact between two atoms is a direct contact without being interrupted by any
      other atom between them. A beta contact's potential contribution to protein
      binding is also supposed to be inversely proportional to its ASA to follow the
      water exclusion hypothesis of binding hot spots. Tested on a dataset of 396
      alanine mutations, our method is found to be superior in classification
      performance to many other methods, including Robetta, FoldX, HotPOINT, an ACV
      method of beta contacts without ASA integration, and ACVASA methods (similar to
      betaACVASA but based on distance-cutoff contacts). Based on our data analysis and
      results, we can draw conclusions that: (i) our method is powerful in the
      prediction of binding free energy change after alanine mutation; (ii) beta
      contacts are better than distance-cutoff contacts for modeling the well-organized
      protein-binding interfaces; (iii) beta contacts usually are only a small fraction
      number of the distance-based contacts; and (iv) water exclusion is a necessary
      condition for a residue to become a binding hot spot. CONCLUSIONS: betaACVASA is
      designed using the advantages of both beta contacts and water exclusion. It is an
      excellent tool to predict binding free energy changes and binding hot spots after
      alanine mutation.

PMID- 24568582
TI  - The acidic ribosomal stalk proteins are not required for the highly specific
      inactivation exerted by alpha-sarcin of the eukaryotic ribosome.
AB  - The ribosomal sarcin/ricin loop (SRL) is the target of ribosome-inactivating
      proteins like the N-glycosidase ricin and the fungal ribotoxin alpha-sarcin. The
      eukaryotic ribosomal stalk directly interacts with several members of the N
      glycosidase family, favoring their disruption of the SRL. Here we tested this
      hypothesis for the ribotoxin alpha-sarcin. Experiments with isolated ribosomes,
      cell-free translation systems, and viability assays with Saccharomyces cerevisiae
      strains defective in acidic stalk proteins showed that the inactivation exerted
      by alpha-sarcin is independent of the composition of the ribosomal stalk.
      Therefore, alpha-sarcin, with the same ribosomal target as ricin, seems to access
      the SRL by a different pathway.

PMID- 24568583
TI  - Adapting to test structure: letting testing teach what to learn.
AB  - We propose that we encode and store information as a function of the particular
      ways we have used similar information in the past. More specifically, we contend
      that the experience of retrieval can serve as a powerful cue to the most
      effective ways to encode similar information in comparable future learning
      episodes. To explore these ideas, we did two studies in which all participants
      went through study-test cycles of single category lists while we manipulated the
      nature of the recognition tests. The recognition tests either included only same
      category lures or only different-category lures. The experience of repeated
      testing leads participants to avoid conceptual-based strategies but only when
      conceptual knowledge was poorly diagnostic for recognition (i.e., in the same
      category lures condition). In a second study with a similar manipulation, we
      showed that repeated testing with lures from the same category as study items
      improved performance in a final recall surprise test compared to conditions in
      which different-category lures were used. Such a difference is akin to the one
      obtained when encoding instructions focus on distinctive item features compared
      to cases in which the focus is on relational processing. We suggest that testing
      requirements lead to adaptive changes at encoding. 

PMID- 24568585
TI  - Human CDC2-like kinase 1 (CLK1): a novel target for Alzheimer's disease.
AB  - The cdc2-like kinases (CLKs) are an evolutionarily conserved group of dual
      specificity kinases belonging to the CMGC (cyclin-dependent kinases (CDKs),
      mitogen-activated protein kinases (MAP kinases), glycogen synthase kinases (GSK)
      and CDK-like kinases). The CLK family consists of four isoforms namely CLK1,
      CLK2, CLK3 and CLK4. The human CLK1 encoded protein comprises 454 amino acids and
      the catalytic domain of CLK1 exhibits the typical protein kinase fold. CLK1 has
      been shown to autophosphorylate on serine, threonine and tyrosine residues and
      phosphorylate exogenous substrates on serine and threonine residues. CLK1 plays
      an important role in the regulation of RNA splicing through phosphorylation of
      members of the serine and arginine-rich (SR) family of splicing factors. CLK1 is
      involved in the pathophysiology of Alzheimer's disease by phosphorylating the
      serine residue in SR proteins. Nuclear speckles of the nucleoplasm contain the
      stored form of SR proteins and are moderately responsible for the choice of
      splicing sites during pre-mRNA splicing. Hence, the inhibition of CLK1 can be
      used as a therapeutic strategy for Alzheimer's disease. Many natural and
      synthetic molecules are reported to possess CLK1 inhibitory activity. Some
      specific examples are Marine alkaloid Leucettamine B and KH-CB19. Leucettamine B
      is a potent inhibitor of CLK1 (15 nM), Dyrk1A (40 nM), and Dyrk2 (35 nM) and a
      moderate inhibitor of CLK3 (4.5 uM) whereas KH-CB19 is a highly specific and
      potent inhibitor of the CLK1/CLK4. X-ray crystallographic studies have revealed
      the binding mode of marine sponge metabolite hymenialdisine and a dichloroindolyl
      enamino nitrile (KH-CB19) to CLK1. This review focuses on the role of CLKs in the
      pathophysiology of Alzheimer's disease and therapeutic potential of targeting
      CLK1 in Alzheimer's disease drug discovery and development. In addition, the
      recent developments in drug discovery efforts targeting human CLK1 are also
      highlighted. 

PMID- 24568584
TI  - Microporous dermal-like electrospun scaffolds promote accelerated skin
      regeneration.
AB  - The goal of this study was to synthesize skin substitutes that blend native
      extracellular matrix (ECM) molecules with synthetic polymers which have favorable
      mechanical properties. To this end, scaffolds were electrospun from collagen I
      (col) and poly(E-caprolactone) (PCL), and then pores were introduced mechanically
      to promote fibroblast infiltration, and subsequent filling of the pores with ECM.
      A 70:30 col/PCL ratio was determined to provide optimal support for dermal
      fibroblast growth, and a pore diameter, 160 MUm, was identified that enabled
      fibroblasts to infiltrate and fill pores with native matrix molecules, including
      fibronectin and collagen I. Mechanical testing of 70:30 col/PCL scaffolds with
      160 MUm pores revealed a tensile strength of 1.4 MPa, and the scaffolds also
      exhibited a low rate of contraction (<19%). Upon implantation, scaffolds should
      support epidermal regeneration; we, therefore, evaluated keratinocyte growth on
      fibroblast-embedded scaffolds with matrix-filled pores. Keratinocytes formed a
      stratified layer on the surface of fibroblast-remodeled scaffolds, and staining
      for cytokeratin 10 revealed terminally differentiated keratinocytes at the apical
      surface. When implanted, 70:30 col/PCL scaffolds degraded within 3-4 weeks, an
      optimal time frame for degradation in vivo. Finally, 70:30 col/PCL scaffolds with
      or without 160 MUm pores were implanted into full-thickness critical-sized skin
      defects. Relative to nonporous scaffolds or sham wounds, scaffolds with 160 MUm
      pores induced accelerated wound closure, and stimulated regeneration of healthy
      dermal tissue, evidenced by a more normal-appearing matrix architecture, blood
      vessel in-growth, and hair follicle development. Collectively, these results
      suggest that microporous electrospun scaffolds are effective substrates for skin
      regeneration.

PMID- 24568586
TI  - Single-port laparoscopic percutaneous extraperitoneal closure using an innovative
      apparatus for pediatric inguinal hernia.
AB  - BACKGROUND: Laparoscopic procedures for pediatric inguinal hernia (PIH) have
      numerous techniques and continue to evolve, with a trend toward increasing use of
      extracorporeal knotting and decreasing use of working ports and endoscopic
      instruments. Single-port laparoscopic percutaneous extraperitoneal closure
      (SPLPEC) with variable devices seems to be one of the most simple and reliable
      methods. Here the authors describe and evaluate the applicable effects of SPLPEC
      using an innovative two-hooked core hernia apparatus. MATERIALS AND METHODS:
      Between June 2008 and October 2011, 72 children with indirect inguinal hernia
      underwent SPLPEC with an innovative two-hooked core hernia apparatus. A 5-mm
      laparoscope was placed through a transumbilical port. Without an assistant
      working port, the two-hooked core hernia apparatus with a 2-0 nonabsorbable
      suture was inserted at the point of the internal inguinal ring. It could be
      readily kept in an identical subcutaneous path for introducing and withdrawing
      the suture. The extraperitoneal knot-tying could tautly enclose the hernia defect
      without peritoneal gaps and upper subcutaneous tissues. During the same period,
      63 cases with PIH underwent SPLPEC with a single-hooked hernia device. Technical
      essentials, mean operation time, and intra- and postoperative complications were
      compared. RESULTS: The internal orifice was closed faster by SPLPEC with the
      innovative two-hooked core apparatus than with a single-hooked device
      (unilateral, 13.21+/-3.86 versus 17.92+/-4.37 minutes [P<.05]; bilateral, 17.18+/
      4.69 versus 25.36+/-7.38 minutes [P<.01]). There were no postoperative
      complications or evidence of early recurrence in the two-hooked group. However,
      one recurrence and one subcutaneous knot granuloma were postoperatively observed
      in the single-hooked group. CONCLUSIONS: SPLPEC with the two-hooked core
      apparatus was proved to be a successful procedure without leaving a peritoneal
      gap and ligating subcutaneous tissues. It is safe, feasible, and reliable for
      PIH.

PMID- 24568587
TI  - Medicinal chemistry optimization of antiplasmodial imidazopyridazine hits from
      high throughput screening of a SoftFocus kinase library: part 1.
AB  - A novel class of imidazopyridazines identified from whole cell screening of a
      SoftFocus kinase library was synthesized and evaluated for antiplasmodial
      activity against K1 (multidrug resistant strain) and NF54 (sensitive strain).
      Structure-activity relationship studies led to the identification of highly
      potent compounds against both strains. Compound 35 was highly active (IC50: K1 =
      6.3 nM, NF54 = 7.3 nM) and comparable in potency to artesunate, and 35 exhibited
      98% activity in the in vivo P. berghei mouse model (4-day test by Peters) at 4 *
      50 mg/kg po. Compound 35 was also assessed against P. falciparum in the in vivo
      SCID mouse model where the efficacy was found to be more consistent with the in
      vitro activity. Furthermore, 35 displayed high (78%) rat oral bioavailability
      with good oral exposure and plasma half-life. Mice exposure at the same dose was
      10-fold lower than in rat, suggesting lower oral absorption and/or higher
      metabolic clearance in mice. 

PMID- 24568588
TI  - Dynamic kinetic resolution based asymmetric transfer hydrogenation of alpha
      alkoxy-beta-ketophosphonates. Diastereo- and enantioselective synthesis of
      monoprotected 1,2-dihydroxyphosphonates.
AB  - Dynamic kinetic resolution driven, asymmetric transfer hydrogenation reactions of
      a wide range of 2-substituted alpha-alkoxy-beta-ketophosphonates 3 were observed
      to proceed efficiently to give the corresponding 2-substituted alpha-alkoxy-beta
      hydroxy phosphonates 4 with excellent levels of diastereo- and
      enantioselectivity. These processes are promoted by using well-defined,
      commercially available, chiral transition metal catalysts and a 0.2:1 mixture of
      formic acid and triethylamine as the hydrogen source and solvent. 

PMID- 24568589
TI  - A real-time locating system observes physician time-motion patterns during walk
      rounds: a pilot study.
AB  - BACKGROUND: Walk-rounds, a common component of medical education, usually consist
      of a combination of teaching outside the patient room as well as in the presence
      of the patient, known as bedside teaching. The proportion of time dedicated to
      bedside teaching has been declining despite research demonstrating its benefits.
      Increasing complexities of patient care and perceived impediments to workflow are
      cited as reasons for this declining use. Research using real-time locating
      systems (RTLS) has been purported to improve workflow through monitoring of
      patients and equipment. We used RTLS technology to observe and track patterns of
      movement of attending physicians during a mandatory once-weekly medical teaching
      team patient care rounding session endorsed as a walk-rounds format. METHODS:
      During a project to assess the efficacy of RTLS technology to track equipment and
      patients in a clinical setting, we conducted a small-scale pilot study to observe
      attending physician walk-round patterns during a mandatory once-weekly team
      rounding session. A consecutive sample of attending physicians on the unit was
      targeted, eight agreed to participate. Data collected using the RTLS were
      pictorially represented as linked points overlaying a floor plan of the unit to
      represent each physician's motion through time. Visual analysis of time-motion
      was independently performed by two researchers and disagreement resolved through
      consensus. Rounding events were described as a sequence of approximate
      proportions of time engaged within or outside patient rooms. RESULTS: The patient
      care rounds varied in duration from 60 to 425 minutes. Median duration of rounds
      within patient rooms was approximately 33% of total time (range approximately 20
      50%). Three general time-motion rounding patterns were observed: a first pattern
      that predominantly involved rounding in ward hallways and little time in patient
      rooms; a second pattern that predominantly involved time in a ward conference
      room; and a third balanced pattern characterized by equal proportions of time in
      patient rooms and in ward hallways. CONCLUSIONS: Observation using RTLS
      technology identified distinct time-motion rounding patterns that hint at
      differing rounding styles across physicians. Future studies using this technology
      could examine how the division of time during walk-rounds impacts outcomes such
      as patient satisfaction, learner satisfaction, and physician workflow.

PMID- 24568590
TI  - Central pulse pressure amplification is associated with more extensive and severe
      coronary artery disease.
AB  - OBJECTIVES: We investigate the association between noninvasively determined
      central pulse waveform characteristics and the extent and severity of coronary
      artery disease (CAD) in patients undergoing coronary angiography with the
      clinical diagnosis of CAD. DESIGN: We included 145 consecutive patients with
      stable angina pectoris (SAP), unstable angina pectoris (USAP), or acute
      myocardial infarction (AMI) who were decided to undergo coronary angiography.
      Gensini and SYNTAX scores were calculated. Noninvasive PWA was performed with the
      SphygmoCor system. RESULTS: Dividing the patients into tertiles according to
      augmentation index (AIx), more patients had significant CAD with higher Gensini
      and SYNTAX scores and lower myocardial blush grade (MBG) (p < 0.001 for all) in
      the third tertile. The AIx value to predict the presence of moderate to severe
      CAD as determined by SYNTAX score >= 23 was 24.45% (ROC analysis AUC: 0.96;
      sensitivity 88%, specificity: 93%, 95% CI: 0.93-0.99, p < 0.001). AIx was
      significantly correlated with Gensini and SYNTAX scores in SAP, USAP, and AMI
      patients after adjusting for age, gender, height, heart rate, hypertension, and
      diabetes. CONCLUSIONS: Increased AIx is associated with the presence and severity
      of CAD, and it may be used in selected patients during cardiovascular evaluation
      in outpatient settings for risk stratification prior to coronary angiography.

PMID- 24568591
TI  - Prevalence and visual risk factors for falls in bilateral cataract patients in Ho
      Chi Minh City, Vietnam.
AB  - PURPOSE: To determine the prevalence of falls in the 12 months prior to cataract
      surgery and examine the associations between visual and other risk factors and
      falls among older bilateral cataract patients in Vietnam. METHODS: Data collected
      from 413 patients in the week before scheduled cataract surgery included a
      questionnaire and three objective visual tests. RESULTS: The outcome of interest
      was self-reported falls in the previous 12 months. A total of 13% (n = 53) of
      bilateral cataract patients reported 60 falls within the previous 12 months.
      After adjusting for age, sex, race, employment status, comorbidities, medication
      usage, refractive management, living status and the three objective visual tests
      in the worse eye, women (odds ratio, OR, 4.64, 95% confidence interval, CI, 1.85
      11.66), and those who lived alone (OR 4.51, 95% CI 1.44-14.14) were at increased
      risk of a fall. Those who reported a comorbidity were at decreased risk of a fall
      (OR 0.43, 95% CI 0.19-0.95). Contrast sensitivity (OR 0.31, 95% CI 0.10-0.95) was
      the only significant visual test associated with a fall. These results were
      similar for the better eye, except the presence of a comorbidity was not
      significant (OR 0.45, 95% CI 0.20-1.02). Again, contrast sensitivity was the only
      significant visual factor associated with a fall (OR 0.15, 95% CI 0.04-0.53).
      CONCLUSION: Bilateral cataract patients in Vietnam are potentially at high risk
      of falls and in need of falls prevention interventions. It may also be important
      for ophthalmologists and health professionals to consider contrast sensitivity
      measures when prioritizing cataract patients for surgery and assessing their risk
      of falls.

PMID- 24568592
TI  - In vivo durability and safety of rolled acellular dermis in a submucosal pocket
      in pigs.
AB  - Objective : This study explored posterior nasopharyngeal augmentation with an
      acellular dermal matrix sheeting. Design : Evaluation of the persistence and
      safety of a submucosal implant of rolled acellular dermis over a 3-month period
      in a piglet model. Setting : Institute Hills Facility, part of the Mayo Clinic
      Rochester health care facility. Participants : Fifteen 5-week-old domestic
      piglets of unspecified gender. Interventions : Twelve piglets were implanted at
      age 5 weeks with a rolled sheet of acellular dermal matrix (Strattice). Implants
      were inserted in a submucosal pocket in the soft palate. Three piglets underwent
      sham operations, with creation of submucosal pockets without implantation. After
      a 3-month observation period, the palates were harvested for evaluation. Results
      : Grossly, persistence of bulk at the surgical site in 5 of the 12 implanted
      piglets was noted at 3 months. Histologically, no persistence of the dermal
      matrix could be observed. Incorporation and/or resorption of the dermal matrix
      occurred with minimal to no host inflammatory response. Conclusion : This
      experiment demonstrated the safety of a rolled acellular dermal implant in a
      submucosal location in a pig model, without surgical complication, host
      inflammatory reaction, or rejection. Minimal, if any, bulk of the implant
      persisted in the implanted location after 3 months. Although acellular dermal
      matrix sheeting appears to be safe and well-tolerated, it does not offer a long
      term treatment option for posterior pharyngeal augmentation. 

PMID- 24568594
TI  - Bacterial meningitis in adults in Iceland, 1995-2010.
AB  - INTRODUCTION: Bacterial meningitis is a serious disease with a mortality rate of
      15-20% in adults. We conducted a population-based study of bacterial meningitis
      in adults (>= 16 y) in Iceland, 1995-2010. METHODS: Cases were identified based
      on positive bacterial cultures from cerebrospinal fluid (CSF) and/or the ICD
      codes for bacterial meningitis. Medical charts were reviewed and outcomes were
      assessed using the national population registry. The study period was divided
      into 2 equal parts, 1995-2002 and 2003-2010, before and after implementation of
      routine childhood vaccination against serogroup C meningococci, respectively.
      RESULTS: In total, 111 episodes occurred in 110 individuals. The most common
      causative organisms were Neisseria meningitidis (41%) and Streptococcus
      pneumoniae (30%). Only 30% of the patients presented with the classical symptom
      triad of fever, neck stiffness, and an altered mental status. The overall
      incidence was 3.2/100,000 inhabitants/y, and dropped significantly between the
      first and second halves of the study (p = 0.03). This drop was due to a reduced
      incidence of N. meningitidis meningitis: 34 and 12 cases in the first and second
      periods, respectively (p = 0.006). The incidence of meningitis caused by S.
      pneumoniae remained unchanged. The case fatality rates were 18% and 13% in the
      first and second halves of the study, respectively (difference not significant).
      CONCLUSIONS: The incidence of bacterial meningitis has decreased since the
      implementation of meningococcal C vaccination in 2002. However, the case fatality
      rate has remained unchanged.

PMID- 24568593
TI  - Cost-effectiveness of eye care services in Zambia.
AB  - OBJECTIVE: To estimate the cost-effectiveness of cataract surgery and refractive
      error/presbyopia correction in Zambia. METHODS: Primary data on costs and health
      related quality of life were collected in a prospective cohort study of 170
      cataract and 113 refractive error/presbyopia patients recruited from three health
      facilities. Six months later, follow-up data were available from 77 and 41
      patients who had received cataract surgery and spectacles, respectively. Costs
      were determined from patient interviews and micro-costing at the three health
      facilities. Utility values were gathered by administering the EQ-5D quality of
      life instrument immediately before and six months after cataract surgery or
      acquiring spectacles. A probabilistic state-transition model was used to generate
      cost-effectiveness estimates with uncertainty ranges. RESULTS: Utility values
      significantly improved across the patient sample after cataract surgery and
      acquiring spectacles. Incremental costs per Quality Adjusted Life Years gained
      were US$ 259 for cataract surgery and US$ 375 for refractive error correction.
      The probabilities of the incremental cost-effectiveness ratios being below the
      Zambian gross national income per capita were 95% for both cataract surgery and
      refractive error correction. CONCLUSION: In spite of proven cost-effectiveness,
      severe health system constraints are likely to hamper scaling up of the
      interventions.

PMID- 24568596
TI  - Long-term exposure to paraquat alters behavioral parameters and dopamine levels
      in adult zebrafish (Danio rerio).
AB  - Chronic exposure to paraquat (Pq), a toxic herbicide, can result in Parkinsonian
      symptoms. This study evaluated the effect of the systemic administration of Pq on
      locomotion, learning and memory, social interaction, tyrosine hydroxylase (TH)
      expression, dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) levels, and
      dopamine transporter (DAT) gene expression in zebrafish. Adult zebrafish received
      an i.p. injection of either 10 mg/kg (Pq10) or 20 mg/kg (Pq20) of Pq every 3 days
      for a total of six injections. Locomotion and distance traveled decreased at 24 h
      after each injection in both treatment doses. In addition, both Pq10- and Pq20
      treated animals exhibited differential effects on the absolute turn angle.
      Nonmotor behaviors were also evaluated, and no changes were observed in anxiety
      related behaviors or social interactions in Pq-treated zebrafish. However, Pq
      treated animals demonstrated impaired acquisition and consolidation of spatial
      memory in the Y-maze task. Interestingly, dopamine levels increased while DOPAC
      levels decreased in the zebrafish brain after both treatments. However, DAT
      expression decreased in the Pq10-treated group, and there was no change in the
      Pq20-treated group. The amount of TH protein showed no significant difference in
      the treated group. Our study establishes a new model to study Parkinson
      associated symptoms in zebrafish that have been chronically treated with Pq.

PMID- 24568595
TI  - A morphology-based method for the diagnosis of red blood cells parasitized by
      Plasmodium malariae and Plasmodium ovale.
AB  - BACKGROUND: The morphology of red blood cells (RBCs) is altered significantly
      during the maturation stages of malaria parasites, which include ring,
      trophozoite, and schizont. There is dissimilarity in terms of the morphological
      characteristics of parasitized RBCs infected by the 4 species of Plasmodium,
      including falciparum, vivax, malariae, and ovale. This makes the process of
      diagnosis very difficult, which may lead to a wrong treatment method and
      substantial damage to the health of the patient. An innovative technique in
      introduced that accurately defines the shape of parasitized RBCs at each stage of
      infection as a potential method of diagnosis. METHODS: Giemsa-stained thin blood
      films were prepared using blood samples collected from healthy donors as well as
      patients infected with P. malariae and P. ovale. The diameter and thickness of
      healthy and infected RBCs at each stage of infection were measured from their
      optical images using Olysia and Scanning Probe Image Processor (SPIP) software,
      respectively. A shape equation was fitted based on the morphological
      characteristics of RBCs, and their relative 2-dimensional shapes were plotted
      using Wolfram Mathematica. RESULTS: At the ring stage, the thicknesses of RBCs
      parasitized by P. malariae (Pm-RBCs) and P. ovale (Po-RBCs) increased by 42% and
      51%, respectively. Both Pm-RBCs and Po-RBCs remained nearly biconcave throughout
      parasite development even though their volumes increased. CONCLUSIONS: It is
      proposed that the morphology-based characterization technique introduced here
      could be used to intensify the accuracy of the Giemsa staining diagnosis method
      for the detection of the Plasmodium genus and infection stage. Based on the
      significant morphological alterations induced by different Plasmodium species,
      the results may also find practical use for faster prediction and treatment of
      human malaria.

PMID- 24568597
TI  - Identification of FISH biomarkers to detect chromosome abnormalities associated
      with prostate adenocarcinoma in tumour and field effect environment.
AB  - BACKGROUND: To reduce sampling error associated with cancer detection in prostate
      needle biopsies, we explored the possibility of using fluorescence in situ
      hybridisation (FISH) to detect chromosomal abnormalities in the histologically
      benign prostate tissue from patients with adenocarcinoma of prostate. METHODS:
      Tumour specimens from 33 radical prostatectomy (RP) cases, histologically benign
      tissue from 17 of the 33 RP cases, and 26 benign prostatic hyperplasia (BPH)
      control cases were evaluated with Locus Specific Identifier (LSI) probes MYC
      (8q24), LPL (8p21.22), and PTEN (10q23), as well as with centromere enumerator
      probes CEP8, CEP10, and CEP7. A distribution of FISH signals in the tumour and
      histologically benign adjacent tissue was compared to that in BPH specimens using
      receiver operating characteristic curve analysis. RESULTS: The combination of MYC
      gain, CEP8 Abnormal, PTEN loss or chromosome 7 aneusomy was positive in the
      tumour area of all of the 33 specimens from patients with adenocarcinomas, and in
      88% of adjacent histologically benign regions (15 out of 17) but in only 15% (4
      out of 26) of the benign prostatic hyperplasia control specimens. CONCLUSIONS: A
      panel of FISH markers may allow detection of genomic abnormalities that associate
      with adenocarcinoma in the field adjacent to and surrounding the tumour, and thus
      could potentially indicate the presence of cancer in the specimen even if the
      cancer focus itself was missed by biopsy and histology review.

PMID- 24568598
TI  - High throughput synthetic lethality screen reveals a tumorigenic role of
      adenylate cyclase in fumarate hydratase-deficient cancer cells.
AB  - BACKGROUND: Synthetic lethality is an appealing technique for selectively
      targeting cancer cells which have acquired molecular changes that distinguish
      them from normal cells. High-throughput RNAi-based screens have been successfully
      used to identify synthetic lethal pathways with well-characterized tumor
      suppressors and oncogenes. The recent identification of metabolic tumor
      suppressors suggests that the concept of synthetic lethality can be applied to
      selectively target cancer metabolism as well. RESULTS: Here, we perform a high
      throughput RNAi screen to identify synthetic lethal genes with fumarate hydratase
      (FH), a metabolic tumor suppressor whose loss-of-function has been associated
      with hereditary leiomyomatosis and renal cell carcinoma (HLRCC). Our unbiased
      screen identified synthetic lethality between FH and several genes in heme
      metabolism, in accordance with recent findings. Furthermore, we identified an
      enrichment of synthetic lethality with adenylate cyclases. The effects were
      validated in an embryonic kidney cell line (HEK293T) and in HLRCC-patient derived
      cells (UOK262) via both genetic and pharmacological inhibition. The reliance on
      adenylate cyclases in FH-deficient cells is consistent with increased cyclic-AMP
      levels, which may act to regulate cellular energy metabolism. CONCLUSIONS: The
      identified synthetic lethality of FH with adenylate cyclases suggests a new
      potential target for treating HLRCC patients.

PMID- 24568599
TI  - Missed foot fractures in polytrauma patients: a retrospective cohort study.
AB  - BACKGROUND: Missed foot fractures are a known problem in the care of the
      traumatized patient. They do not usually have an influence on the survival, but
      on the long-term result and the quality of the patient's life. The aim of this
      study is to find out how many of these fractures are overlooked in a Level I
      trauma center and what the consequences for the patients are hypothesing that
      patients with a delayed diagnosis will have worse clinical results. METHODS:
      Forty-seven patients (7.3%) with foot fractures could be identified in 642
      polytrauma patients, retrospectively. All patients were divided into two groups:
      early diagnosed fractures and delayed diagnosed fractures, the latter defined as
      diagnosed after Secondary Survey. Patients were evaluated according to the
      Hannover Outcome Score, the Short Form-36 Health Survey, the AOFAS Score and the
      Hannover Scoring System. The average follow-up was 5 years and 8 months. Reasons
      for overlooking a foot fracture were analyzed. RESULTS: The foot fracture was
      early diagnosed in 26 (55.3%) patients, but delayed in 21 (44.7%). There were no
      significant differences in the mean stay in the hospital or in the ICU. The
      fractures that were most often missed were those of the cuboid or the metarsalia.
      The highest risk factor for a delayed diagnosis was a fracture already diagnosed
      on the same foot. In 52.4% of the delayed diagosed fractures, an operative
      therapy was necessary. There were no significant differences between the two
      groups in the clinical results. CONCLUSIONS: In summary, the results of this
      study show that foot injuries can be a safety problem for the patient and the
      examination of the feet in the trauma room has to be a compulsory part of the
      algorithm. Although the majority of delayed diagnosed foot fractures demonstrated
      comparable results to the immediately diagnosed fractures, approximately 10%
      might have benefited from an earlier diagnosis. Even if there were no significant
      differences in the clinical results, we have to be aware that missing a fracture
      in the foot can lead to worse results in the complete polytrauma care.

PMID- 24568600
TI  - Benchmarking infrastructure for mutation text mining.
AB  - BACKGROUND: Experimental research on the automatic extraction of information
      about mutations from texts is greatly hindered by the lack of consensus
      evaluation infrastructure for the testing and benchmarking of mutation text
      mining systems. RESULTS: We propose a community-oriented annotation and
      benchmarking infrastructure to support development, testing, benchmarking, and
      comparison of mutation text mining systems. The design is based on semantic
      standards, where RDF is used to represent annotations, an OWL ontology provides
      an extensible schema for the data and SPARQL is used to compute various
      performance metrics, so that in many cases no programming is needed to analyze
      results from a text mining system. While large benchmark corpora for biological
      entity and relation extraction are focused mostly on genes, proteins, diseases,
      and species, our benchmarking infrastructure fills the gap for mutation
      information. The core infrastructure comprises (1) an ontology for modelling
      annotations, (2) SPARQL queries for computing performance metrics, and (3) a
      sizeable collection of manually curated documents, that can support mutation
      grounding and mutation impact extraction experiments. CONCLUSION: We have
      developed the principal infrastructure for the benchmarking of mutation text
      mining tasks. The use of RDF and OWL as the representation for corpora ensures
      extensibility. The infrastructure is suitable for out-of-the-box use in several
      important scenarios and is ready, in its current state, for initial community
      adoption.

PMID- 24568602
TI  - Double J or transrenal transanastomotic stent in laparoscopic pyeloplasty in
      infants and children: a comparative study and our technique.
AB  - PURPOSE: We compared our experience with intra- and extracorporeal stenting in
      laparoscopic transabdominal pyeloplasty in children and adolescents. As the
      placement of transanastomotic stents during laparoscopy can be difficult, we
      developed a technique for laparoscopic transrenal stent placement. SUBJECTS AND
      METHODS: Eighty-six consecutive patients who underwent laparoscopic
      transabdominal pyeloplasty in our institution from December 2003 to November 2012
      were retrospectively analyzed. Initially we antegradely placed the double J
      catheter (n=48), whereas in later patients transrenal/transcutaneous stents were
      inserted (n=38), either via a cannula from the flank (n=33) or from the inside
      out by transrenal puncture using a specially constructed spear (n=5). End points
      of the analysis were stent-related technical problems and complications and the
      need for reoperation. RESULTS: Sixty-two boys and 24 girls with a mean age of 5.6
      years (range, 78 days-17.3 years) and mean weight of 22.1 kg (range, 5.5-71 kg)
      underwent laparoscopic transabdominal pyeloplasty. The most common technical
      problem in the double J group was inability to place the double J catheter in 9
      of the 48 patients. In combination with other complications such as dislocations,
      urinary tract infections, or catheter occlusions, this led to an overall
      complication rate of 35% in the group that underwent double J catheter insertion
      versus 13% in the group with transrenal stenting (P<.05). In the whole series, 4
      patients required a redo pyeloplasty, all of them in the double J group.
      CONCLUSIONS: We recommend transrenal stents to facilitate stent removal without
      general anesthesia and to minimize complications such as stent dislocation. The
      initial experience with our simple device for transrenal puncture and stent
      placement is promising.

PMID- 24568601
TI  - Nogo-B receptor modulates angiogenesis response of pulmonary artery endothelial
      cells through eNOS coupling.
AB  - Nogo-B, a reticulon-4 isoform, modulates the motility and adhesion of vascular
      endothelial cells after binding to its receptor, Nogo-B receptor (NgBR). Nogo
      B/NgBR pathway contributes to vascular remodeling and angiogenesis, but the role
      of this pathway in the angiogenesis of developing lungs remains unknown. We
      previously reported that angiogenesis function of pulmonary artery endothelial
      cells (PAECs) is impaired by increased reactive oxygen species formation in a
      fetal lamb model of intrauterine pulmonary hypertension (IPH). Here, we report
      that Nogo-B/NgBR pathway is altered in IPH, and that decreased NgBR expression
      contributes to impaired angiogenesis in IPH. We observed a decrease in NgBR
      levels in lysates of whole lung or PAECs from fetal lambs with IPH compared with
      controls. Overexpression of NgBR in IPH PAECs rescued the in vitro angiogenesis
      defects and increased the phosphorylation of both Akt and endothelial nitric
      oxide synthase at serine(1179) as well as the levels of both manganese superoxide
      dismutase and GTP cyclohydrolase-1. Consistent with the phenotype of IPH PAECs,
      knockdown of NgBR in control PAECs decreased the levels of nitric oxide,
      increased the levels of reactive oxygen species, and impaired in vitro
      angiogenesis. Our data demonstrate that NgBR mediates PAEC angiogenesis response
      through the modulation of Akt/endothelial nitric oxide synthase functions, and
      its decreased expression is mechanistically linked to IPH-related angiogenesis
      defects in the developing lungs. 

PMID- 24568604
TI  - Electron-donating behavior of few-layer graphene in covalent ensembles with
      electron-accepting phthalocyanines.
AB  - We describe herein the first example of highly exfoliated graphene covalently
      linked to electron accepting phthalocyanines. The functionalization of the
      nanocarbon surface with alkylsulfonyl phthalocyanines was attained by means of a
      "click" chemistry protocol. The new ensemble was fully characterized
      (thermogravimetric analysis, atomic force microscopy, transmission electron
      microscopy and Raman, as well as ground-state absorption) and was studied in
      terms of electron donor-acceptor interactions in the ground and in the excited
      state. In particular, a series of steady-state and time-resolved spectroscopy
      experiments demonstrated photoinduced electron transfer from the graphene to the
      electron-accepting phthalocyanines. This is the first example of an electron
      donor-acceptor nanoconjugate, that is, few-layer graphene/phthalocyanine,
      pinpointing the uncommon electron donating character of graphene. 

PMID- 24568603
TI  - Economic utility of a blood-based genomic test for the assessment of patients
      with symptoms suggestive of obstructive coronary artery disease.
AB  - Approximately 3 million patients with symptoms suggestive of obstructive coronary
      artery disease (CAD) present to primary care offices in the United States
      annually, resulting in approximately $6.7 billion in cardiac workup costs.
      Despite wide application of existing diagnostic technologies, yield of
      obstructive CAD at invasive coronary angiography (ICA) is low. This study used a
      decision analysis model to assess the economic utility of a novel gene expression
      score (GES) for the diagnosis of obstructive CAD. Within a representative
      commercial health plan's adult membership, current practice for obstructive CAD
      diagnosis (usual care) was compared to a strategy that incorporates the GES test
      (GES-directed care). The model projected the number of diagnostic tests and
      procedures performed, the number of patients receiving medical therapy, type I
      and type II errors for each strategy of obstructive CAD diagnosis, and the
      associated costs over a 1-year time horizon. Results demonstrate that GES
      directed care to exclude the diagnosis of obstructive CAD prior to myocardial
      perfusion imaging may yield savings to health plans relative to usual care by
      reducing utilization of noninvasive and invasive cardiac imaging procedures and
      increasing diagnostic yield at ICA. At a 50% capture rate of eligible patients in
      GES-directed care, it is projected that a commercial health plan will realize
      savings of $0.77 per member per month; savings increase proportionally to the GES
      capture rate. These findings illustrate the potential value of this new blood
      based, molecular diagnostic test for health plans and patients in an age of
      greater emphasis on personalized medicine.

PMID- 24568605
TI  - A two-stage microbial fuel cell and anaerobic fluidized bed membrane bioreactor
      (MFC-AFMBR) system for effective domestic wastewater treatment.
AB  - Microbial fuel cells (MFCs) are a promising technology for energy-efficient
      domestic wastewater treatment, but the effluent quality has typically not been
      sufficient for discharge without further treatment. A two-stage laboratory-scale
      combined treatment process, consisting of microbial fuel cells and an anaerobic
      fluidized bed membrane bioreactor (MFC-AFMBR), was examined here to produce high
      quality effluent with minimal energy demands. The combined system was operated
      continuously for 50 days at room temperature (~25  degrees C) with domestic
      wastewater having a total chemical oxygen demand (tCOD) of 210 +/- 11 mg/L. At a
      combined hydraulic retention time (HRT) for both processes of 9 h, the effluent
      tCOD was reduced to 16 +/- 3 mg/L (92.5% removal), and there was nearly complete
      removal of total suspended solids (TSS; from 45 +/- 10 mg/L to <1 mg/L). The
      AFMBR was operated at a constant high permeate flux of 16 L/m(2)/h over 50 days,
      without the need or use of any membrane cleaning or backwashing. Total electrical
      energy required for the operation of the MFC-AFMBR system was 0.0186 kWh/m(3),
      which was slightly less than the electrical energy produced by the MFCs (0.0197
      kWh/m(3)). The energy in the methane produced in the AFMBR was comparatively
      negligible (0.005 kWh/m(3)). These results show that a combined MFC-AFMBR system
      could be used to effectively treat domestic primary effluent at ambient
      temperatures, producing high effluent quality with low energy requirements. 

PMID- 24568606
TI  - Disseminating a cervical cancer screening program through primary physicians in
      Hong Kong: a qualitative study.
AB  - BACKGROUND: Organized screening programs are more effective and equitable than
      opportunistic screening, yet governments face challenges to implement evidence
      based programs. The objective of this study was to identify reasons for low
      levels of adoption among primary care physicians of a government sponsored
      Cervical Screening Program (CSP). METHODS: We conducted in-depth interviews with
      a snowball sample of primary care private and public primary care physicians in
      Hong Kong. Rogers' theory of diffusion of innovation was used to understand the
      factors that influenced the physicians' practice decisions. RESULTS: Our study
      found that Hong Kong physicians made the decision to encourage cervical screening
      and to participate in the CSP based primarily upon their clinical and business
      practice needs rather than upon the scientific evidence. The low rates of
      adoption of the CSP can be attributed to the physicians' perceptions that the
      program's complexity and incompatibility exceeded its relative advantages.
      Furthermore, women's knowledge, attitudes and practices, identified as barriers
      by physicians, were also barriers to physicians adopting the CSP. CONCLUSIONS: In
      both private and public health care systems, screening programs that rely on
      physicians must align program incentives with the physicians' motivators or
      pursue additional demand creation policies to achieve objectives.

PMID- 24568608
TI  - Use of DMPC and DSPC lipids for verapamil and naproxen permeability studies by
      PAMPA.
AB  - Verapamil and naproxen Parallel Artificial Membrane Permeability Assay (PAMPA)
      permeability was studied using lipids not yet reported for this model in order to
      facilitate the quantification of drug permeability. These lipids are 1,2
      distearoyl-sn-glycero-3-phosphatidylcholine (DSPC), 1,2-dimyristoyl-sn-glycero-3
      phosphocholine (DMPC) and an equimolar mixture of DMPC/DSPC, both in the absence
      and in the presence of 33.3 mol% of cholesterol. PAMPA drug permeability using
      the lipids mentioned above was compared with lecithin-PC. The results show that
      verapamil permeability depends on the kind of lipid used, in the order DMPC >
      DMPC/DSPC > DSPC. The permeability of the drugs was between 1.3 and 3.5-times
      larger than those obtained in lecithin-PC for all the concentrations of the drug
      used. Naproxen shows similar permeability than verapamil; however, the
      permeability increased with respect to lecithin-PC only when DMPC and DMPC/DSPC
      were used. This behavior could be explained by a difference between the drug net
      charge at pH 7.4. On the other hand, in the presence of cholesterol, verapamil
      permeability increases in all lipid systems; however, the relative verapamil
      permeability respect to lecithin-PC did not show any significant increase. This
      result is likely due to the promoting effect of cholesterol, which is not able to
      compensate for the large increase in verapamil permeability observed in lecithin
      PC. With respect to naproxen, its permeability value and relative permeability
      respect lecithin-PC not always increased in the presence of cholesterol. This
      result is probably attributed to the negative charge of naproxen rather than its
      molecular weight. The lipid systems studied have an advantage in drug
      permeability quantification, which is mainly related to the charge of the
      molecule and not to its molecular weight or to cholesterol used as an absorption
      promoter. 

PMID- 24568607
TI  - Collagen-GAG scaffold biophysical properties bias MSC lineage choice in the
      presence of mixed soluble signals.
AB  - Biomaterial strategies for regenerating multitissue structures require unique
      approaches. One strategy is to design scaffolds so that their local biophysical
      properties can enhance site-specific effects of an otherwise heterogeneous
      biomolecular environment. This investigation examined the role of biomaterial
      physical properties (relative density, mineral content) on the human mesenchymal
      stem cell phenotype in the presence of mixed soluble signals to drive
      osteogenesis or chondrogenesis. We tested a series of three-dimensional collagen
      glycosaminoglycan scaffolds with properties inspired by extracellular matrix
      characteristics across the osteotendinous interface (tendon, cartilage, and
      bone). We found that selective scaffold mineralization induced a depressed
      chondrogenic response compared with nonmineralized groups as demonstrated by gene
      expression and histological analyses. Interestingly, the greatest chondrogenic
      response was found in a higher density, nonmineralized scaffold variant despite
      increased contraction and cellular condensation in lower density nonmineralized
      scaffolds. In fact, the lower density scaffolds demonstrated a significantly
      higher expression of osteogenic transcripts as well as ample mineralization after
      21 days of culture. This effect may be due to local stiffening of the scaffold
      microenvironment as the scaffold contracts, leading to increased cell density,
      accelerated differentiation, and possible endochondral ossification as evidenced
      by a transition from a glycosaminoglycan (GAG)-rich milieu to higher
      mineralization at later culture times. These findings will help shape the design
      rules for graded biomaterials to regenerate distinct fibrillar,
      fibrocartilagenous, and mineralized regions of orthopedic interfaces. 

PMID- 24568609
TI  - In vitro evaluation and in vivo performance of lyophilized gliclazide.
AB  - Enhancement of the dissolution rate of the poorly water-soluble hypoglycemic
      agent, gliclazide, by the aid of lyophilization was investigated. Mannitol,
      sodium lauryl sulfate (SLS) and polyvinyl pyrrolidone (PVP-k-30) were employed in
      different weight ratios (43%, 56% and 64% w/w, respectively) as water-soluble
      excipients in the formulation. Lyophilized systems were found to exhibit
      extremely higher in vitro dissolution rate compared to the unprocessed drug
      powder. Solid state characterization of the lyophilized systems using X-ray
      powder diffraction, Fourier transform infrared spectroscopy and differential
      scanning calorimetry techniques revealed that dissolution enhancement was
      attributable to transformation of gliclazide from the crystalline to an amorphous
      state in the solid dispersion formed during the lyophilization process. The
      gastrointestinal absorption and hypoglycemic effect of the lyophilized
      gliclazide/SLS system were investigated following oral administration to Albino
      rabbits. Cmax and area under the plasma concentration-time curve of gliclazide
      (AUC0-12) after administration of the lyophilized formulations were significantly
      higher than those obtained after administration of the unprocessed gliclazide. 

PMID- 24568610
TI  - Posttranslational modifications of defined embryonic reprogramming transcription
      factors.
AB  - The generation of induced pluripotent stem cells (iPSCs) from somatic cells by
      expressing ectopic reprogramming transcriptional factors such as Oct3/4, Sox2,
      Klf4, c-Myc, and Nanog is one of the cutting-edge discoveries in stem cell and
      cancer research. This discovery has raised several safety issues regarding the
      use of iPSC technology for human disease research. Tumorigenesis is the major
      obstacle observed for iPSC-mediated transplantation therapy. Recently, a new
      method to generate human iPSCs either by a chemical method or by direct delivery
      of reprogramming factors has become a promising approach for future customized
      cell therapy of human disorders. These reprogramming transcriptional factors play
      critical roles in diverse cellular functions such as transactivation, cellular
      proliferation, differentiation, apoptosis, and tumorigenesis. Posttranslational
      modifications (PTMs) (phosphorylation, ubiquitination, acetylation, sumoylation,
      and so on) of these proteins act as a regulatory signal to control protein
      activity, expression, and stability in a wide variety of cellular processes. We
      attempt to summarize the accumulated evidence to address the role of PTMs of
      Oct3/4, Sox2, Klf4, c-Myc, and Nanog in regulating their biological functions.
      This review allows us to understand the importance of PTMs and their application
      in developing an efficient and safe reprogramming method without cancer
      development for cell therapy. Finally, we discuss the importance of PTMs of
      reprogramming factors in tumor pathogenesis.

PMID- 24568611
TI  - Individual characteristics associated with physical activity intervention
      delivery mode preferences among adults.
AB  - BACKGROUND: People have different preferences on how health behaviour change
      interventions are delivered to them; intervention implementation, retention and
      effectiveness may be improved if preferences can be matched. PURPOSE: This study
      aims to explore factors related to preference of face-to-face, and group-, print-
      or web-based physical activity intervention delivery modes among adults recruited
      from the general population. METHODS: A question relating to physical activity
      intervention preference was included in the telephone administered 2010
      Queensland Social Survey. Multinomial regression models were used to explore
      socio-demographic (e.g., age, marital status, location), health (e.g., BMI,
      chronic disease status) and behavioral factors (e.g., internet use, physical
      activity, diet, social networking) related to intervention preferences, using 'a
      face-to-face intervention' as the reference category. RESULTS: 35.2% of those
      approached took part in the telephone interviews (n=1,261). Preference for a web
      based intervention was positively associated with being in the 35-44 age group
      (compared to the 18-34 age group; RR=2.71), living in a rural area (RR=2.01), and
      high internet use (RR=1.03); and negatively associated with female gender
      (RR=0.52), obesity (RR=0.42), and higher physical activity participation
      (RR=0.99). Preference for a print-based intervention was positively associated
      with older age (RR=5.50); and negatively associated with female gender (RR=0.48)
      and obesity (RR=0.47). Preference for a group-based program was positively
      associated with living in a regional town (RR=1.48) and negatively associated
      with being separated (RR=0.45) and obesity (RR =0.56). CONCLUSION: Findings from
      this study help to delineate what physical activity intervention delivery modes
      are likely to be appealing for specific target groups, especially in relation to
      people of different weight status, age, gender and living environment. As such,
      this information will be useful in the development of interventions targeted at
      these groups.

PMID- 24568612
TI  - Rationale, design, and demographic characteristics of the Handan Offspring Myopia
      Study.
AB  - PURPOSE: The Handan Offspring Myopia Study (HOMS) aims to investigate the
      familial associations of myopia between parents and their offspring. METHODS:
      Children aged 6-18 years, residing in 6 villages where all people aged >=30 years
      had participated in The Handan Eye Study in 2006-2007, were selected for the
      current eye study between March and June 2010. A mobile clinic was set up in the
      6 villages for comprehensive eye examinations, including visual acuity, ocular
      biometry, cycloplegic autorefraction and retinal photography. RESULTS: Of 1238
      eligible individuals, 878 children (70.2%; 52.6% male) from 541 families were
      recruited. Mean age of the children was 10.5 +/- 2.5 years. The prevalence of
      myopia (spherical equivalent refraction <-0.5 diopter) was 23.5% (males 16.8%,
      females 30.8%). The prevalence of low vision (presenting visual acuity >=20/400
      but <20/60) in the better eye was 7.1%. A higher number of females had low vision
      at the time of presentation (9.2%) compared to males (5.2%, p = 0.02). The
      prevalence of low vision in the worse eye was 10.6% (males 6.7%, females 14.9%, p
      < 0.001). The majority of visual impairment in the better-seeing (56/62, 90.3%)
      as well as the worse-seeing (84/93, 90.3%) eye was correctable. CONCLUSIONS: The
      HOMS examined about 70% of eligible Han Chinese offspring of Handan Eye Study
      participants in a rural region of northern China. Results from the HOMS will
      provide key information about the prevalence of refractive errors and eye
      diseases in rural Chinese children.

PMID- 24568613
TI  - Effect of inhaled endotoxin on mucociliary clearance and airway inflammation in
      mild smokers and nonsmokers.
AB  - BACKGROUND: In healthy nonsmokers, inhaled endotoxin [lipopolysaccharide (LPS)]
      challenge induces airway neutrophilia and modifies innate immune responses, but
      the effect on mucociliary clearance (MCC), a key host defense response, is
      unknown. Although smokers are chronically exposed to LPS through inhaled tobacco
      smoke, the acute effect of inhaled LPS on both MCC and airway inflammation is
      also unknown. The purpose of this study was to determine the effect of inhaled
      LPS on MCC in nonsmokers and mild smokers with normal pulmonary function.
      METHODS: We performed an open-label inhalational challenge with 20,000 endotoxin
      units in healthy adult nonsmokers (n=18) and young adult, mild smokers (n=12). At
      4 hr post LPS challenge, we measured MCC over a period of 2 hr, followed by
      sputum induction to assess markers of airway inflammation. RESULTS: No
      significant changes in spirometry occurred in either group following LPS
      challenge. Following LPS, MCC was significantly (p<0.05) slowed in nonsmokers,
      but not in smokers [MCC=10+/-9% (challenge) vs. 15+/-8% (baseline), MCC=14+/-9%
      (challenge) vs. 16+/-10% (baseline), respectively]. Both groups showed a
      significant (p<0.05) increase in sputum neutrophils 6 hr post LPS challenge
      versus baseline. Although there was no correlation between the increased
      neutrophilia and depressed MCC post LPS in the nonsmokers, baseline neutrophil
      concentration predicted the LPS-induced decrease in MCC in the nonsmokers, i.e.,
      lower baseline neutrophil concentration was associated with greater depression in
      MCC with LPS challenge (p<0.05). CONCLUSIONS: These data show that a mild
      exposure to endotoxin acutely slows MCC in healthy nonsmokers. MCC in mild
      smokers is unaffected by mild endotoxin challenge, likely due to preexisting
      effects of cigarette smoke on their airway epithelium.

PMID- 24568614
TI  - Antiproliferative and uncoupling effects of delocalized, lipophilic, cationic
      gallic acid derivatives on cancer cell lines. Validation in vivo in singenic
      mice.
AB  - Tumor cells principally exhibit increased mitochondrial transmembrane potential
      (DeltaPsi(m)) and altered metabolic pathways. The therapeutic targeting and
      delivery of anticancer drugs to the mitochondria might improve treatment
      efficacy. Gallic acid exhibits a variety of biological activities, and its ester
      derivatives can induce mitochondrial dysfunction. Four alkyl gallate
      triphenylphosphonium lipophilic cations were synthesized, each differing in the
      size of the linker chain at the cationic moiety. These derivatives were
      selectively cytotoxic toward tumor cells. The better compound (TPP(+)C10)
      contained 10 carbon atoms within the linker chain and exhibited an IC50 value of
      approximately 0.4-1.6 MUM for tumor cells and a selectivity index of
      approximately 17-fold for tumor compared with normal cells. Consequently, its
      antiproliferative effect was also assessed in vivo. The oxygen consumption rate
      and NAD(P)H oxidation levels increased in the tumor cell lines (uncoupling
      effect), resulting in a DeltaPsi(m) decrease and a consequent decrease in
      intracellular ATP levels. Moreover, TPP(+)C10 significantly inhibited the growth
      of TA3/Ha tumors in mice. According to these results, the antineoplastic activity
      and safety of TPP(+)C10 warrant further comprehensive evaluation.

PMID- 24568616
TI  - The boson peak of amyloid fibrils: probing the softness of protein aggregates by
      inelastic neutron scattering.
AB  - Proteins and polypeptides are characterized by low-frequency vibrations in the
      terahertz regime responsible for the so-called "boson peak". The shape and
      position of this peak are related to the mechanical properties of peptide chains.
      Amyloid fibrils are ordered macromolecular assemblies, spontaneously formed in
      nature, characterized by unique biological and nanomechanical properties. In this
      work, we investigate the effects of the amyloid state and its polymorphism on the
      boson peak. We used inelastic neutron scattering to probe low-frequency
      vibrations of the glucagon polypeptide in the native state and in two different
      amyloid morphologies in both dry and hydrated sample states. The data show that
      amyloid fibril formation and hydration state affect the softness of the
      polypeptide not only by changing the distribution of vibrational modes but also,
      and most significantly, the dissipative mechanisms of collective low-frequency
      vibrations provided by water-protein and protein-protein interactions. We show
      how the morphology of the fibril is able to tune these effects. Atomic
      fluctuations were also measured by elastic neutron scattering. The data confirm
      that any effect of protein aggregation on fluctuation amplitudes is essentially
      due to changes in surface exposure to hydration water. The results demonstrate
      the importance of protein-protein and protein-water interactions in the dynamics
      and mechanics of amyloid fibrils. 

PMID- 24568615
TI  - Expansion or depletion of T follicular helper cells during HIV infection:
      consequences for B cell responses.
AB  - HIV infection is characterized by aberrant B cell responses and B cell
      dysfunction. These dysfunctional responses have been extensively documented in
      peripheral blood and organized lymphoid tissues such as the lymph nodes. Though
      the loss of CD4 T cell help has been thought to play a key role in dysfunctional
      B cell responses, recent studies have implicated a subset of CD4 T helper cells
      called the T follicular helper (Tfh) cells in this process. Tfh cells interact
      with B cells and play a key role in mediating the germinal center reaction, and
      driving the differentiation and maturation of B cells. Why Tfh expands in some
      HIV infected individuals as compared to their loss in others is still not clear.
      Here we review some of the recent developments in the field and discuss the
      implications of Tfh cell dysregulation on B cell responses during HIV infection. 

PMID- 24568618
TI  - A novel method for detecting inpatient pediatric asthma encounters using
      administrative data.
AB  - Multiple methods for detecting asthma encounters are used today in public
      surveillance, quality reporting, and clinical research. Failure to detect asthma
      encounters can make it difficult to measure the scope and effectiveness of
      hospital or community-based interventions important in comparative effectiveness
      research and accountable care. Given the pairing of asthma with certain
      respiratory conditions, the objective of this study was to develop and test an
      asthma detection algorithm with specificity and sensitivity using 2 criteria: (1)
      principal discharge diagnosis and (2) asthma diagnosis code position. A medical
      record review was conducted (n=191) as the gold standard for identifying asthma
      encounters given objective criteria. The study team observed that for certain
      principal respiratory diagnoses (n=110), the observed odds ratio that encounters
      were for asthma when asthma was coded in the second or third code position was
      not significantly different than when asthma was coded as the principal
      diagnosis, 0.36 (P=0.42) and 0.18 (P=0.14), respectively. In contrast, the
      observed odds ratio was significantly different when asthma was coded in the
      fourth or fifth positions (P<.001). This difference remained after adjusting for
      covariates. Including encounters with asthma in 1 of the 3 first positions
      increased the detection sensitivity to 0.84 [95% confidence interval (CI): 0.76
      0.92] while increasing the false positive rate to 0.19 [95% CI: 0.07-0.31]. Use
      of the proposed algorithm significantly improved the reporting accuracy [0.83
      95%CI:0.76-0.90] over use of (1) the principal diagnosis alone [0.55 95% CI:0.46
      0.64] or (2) all encounters with asthma 0.66 [95% CI:0.57-0.75]. Bed days
      resulting from asthma encounters increased 64% over use of the principal
      diagnosis alone. Given these findings, an algorithm using certain respiratory
      principal diagnoses and asthma diagnosis code position can reliably improve
      asthma encounter detection for population-based health impact measurement.

PMID- 24568617
TI  - Intraocular pressure-lowering efficacy and safety of bimatoprost 0.03% therapy
      for primary open-angle glaucoma and ocular hypertension patients in China.
AB  - BACKGROUND: To report the clinical outcomes in Chinese patients with primary open
      angle glaucoma and ocular hypertension treated with bimatoprost 0.03% therapy.
      METHODS: Two hundred sixty-three Chinese patients with primary open-angle
      glaucoma and ocular hypertension who needed initial or additional intraocular
      pressure (IOP) lowering were recruited in this prospective, open-label,
      multicenter clinical study and were treated with bimatoprost 0.03%. Patients
      received bimatoprost 0.03% as initial, replacement or adjunctive IOP-lowering
      therapy, and follow-up visits were performed at week 1, and month 1 and 3 of the
      bimatoprost treatment. The efficacy outcome measure was the post-treatment IOP
      level. The safety outcome measures included the rate of medication-related
      symptoms, physical signs, reported adverse events, and the level of conjunctival
      hyperemia. RESULTS: Among 240 patients who could be categorized by pre-existing
      therapies and the bimatoprost therapy regimen in the study, IOP values observed
      in all medication conditions showed significant IOP reduction at all study visits
      compared with baseline. At 3 months, 8.0 +/- 3.7 mmHg (32.0%) reduction in IOP
      was observed in treatment-naive patients after bimatoprost monotherapy; in the
      patients previously on various therapy regimens, 1.9 +/- 2.8 mmHg (9.5%) to 6.4
      +/- 6.1 mmHg (24.8%) additional IOP lowering was achieved after switching to
      bimatoprost monotherapy or bimatoprost combination therapy. The most common
      adverse event was conjunctival hyperemia, mainly of trace and mild intensity.
      CONCLUSIONS: Our results show that bimatoprost 0.03% was effective in lowering
      IOP with favorable safety in Chinese primary open-angle glaucoma and ocular
      hypertension patients.

PMID- 24568620
TI  - Impact of physical properties on ozone removal by several porous materials.
AB  - Models of reactive uptake of ozone in indoor environments generally describe
      materials through aerial (horizontal) projections of surface area, a potentially
      limiting assumption for porous materials. We investigated the effect of changing
      porosity/pore size, material thickness, and chamber fluid mechanic conditions on
      the reactive uptake of ozone to five materials: two cellulose filter papers, two
      cementitious materials, and an activated carbon cloth. Results include (1)
      material porosity and pore size distributions, (2) effective diffusion
      coefficients for ozone in materials, and (3) material-ozone deposition velocities
      and reaction probabilities. At small length scales (0.02-0.16 cm) increasing
      thickness caused increases in estimated reaction probabilities from 1 * 10(-6) to
      5 * 10(-6) for one type of filter paper and from 1 * 10(-6) to 1 * 10(-5) for a
      second type of filter paper, an effect not observed for materials tested at
      larger thicknesses. For high porosity materials, increasing chamber transport
      limited deposition velocities resulted in increases in reaction probabilities by
      factors of 1.4-2.0. The impact of physical properties and transport effects on
      values of the Thiele modulus, ranging across all materials from 0.03 to 13, is
      discussed in terms of the challenges in estimating reaction probabilities to
      porous materials in scenarios relevant to indoor environments. 

PMID- 24568619
TI  - Crowning: a novel Escherichia coli colonizing behaviour generating a self
      organized corona.
AB  - BACKGROUND: Encased in a matrix of extracellular polymeric substances (EPS)
      composed of flagella, adhesins, amyloid fibers (curli), and exopolysaccharides
      (cellulose, beta-1,6-N-acetyl-D-glucosamine polymer-PGA-, colanic acid), the
      bacteria Escherichia coli is able to attach to and colonize different types of
      biotic and abiotic surfaces forming biofilms and colonies of intricate
      morphological architectures. Many of the biological aspects that underlie the
      generation and development of these E. coli's formations are largely poorly
      understood. RESULTS: Here, we report the characterization of a novel E. coli
      sessile behaviour termed "crowning" due to the bacterial generation of a new 3-D
      architectural pattern: a corona. This bacterial pattern is formed by joining bush
      like multilayered "coronal flares or spikes" arranged in a ring, which self
      organize through the growth, self-clumping and massive self-aggregation of cells
      tightly interacting inside semisolid agar on plastic surfaces. Remarkably, the
      corona's formation is developed independently of the adhesiveness of the major
      components of E. coli's EPS matrix, the function of chemotaxis sensory system,
      type 1 pili and the biofilm master regulator CsgD, but its formation is
      suppressed by flagella-driven motility and glucose. Intriguingly, this glucose
      effect on the corona development is not mediated by the classical catabolic
      repression system, the cyclic AMP (cAMP)-cAMP receptor protein (CRP) complex.
      Thus, corona formation departs from the canonical regulatory transcriptional core
      that controls biofilm formation in E. coli. CONCLUSIONS: With this novel
      "crowning" activity, E. coli expands its repertoire of colonizing collective
      behaviours to explore, invade and exploit environments whose critical viscosities
      impede flagella driven-motility.

PMID- 24568621
TI  - The zebrafish anatomy and stage ontologies: representing the anatomy and
      development of Danio rerio.
AB  - BACKGROUND: The Zebrafish Anatomy Ontology (ZFA) is an OBO Foundry ontology that
      is used in conjunction with the Zebrafish Stage Ontology (ZFS) to describe the
      gross and cellular anatomy and development of the zebrafish, Danio rerio, from
      single cell zygote to adult. The zebrafish model organism database (ZFIN) uses
      the ZFA and ZFS to annotate phenotype and gene expression data from the primary
      literature and from contributed data sets. RESULTS: The ZFA models anatomy and
      development with a subclass hierarchy, a partonomy, and a developmental hierarchy
      and with relationships to the ZFS that define the stages during which each
      anatomical entity exists. The ZFA and ZFS are developed utilizing OBO Foundry
      principles to ensure orthogonality, accessibility, and interoperability. The ZFA
      has 2860 classes representing a diversity of anatomical structures from different
      anatomical systems and from different stages of development. CONCLUSIONS: The ZFA
      describes zebrafish anatomy and development semantically for the purposes of
      annotating gene expression and anatomical phenotypes. The ontology and the data
      have been used by other resources to perform cross-species queries of gene
      expression and phenotype data, providing insights into genetic relationships,
      morphological evolution, and models of human disease.

PMID- 24568622
TI  - Pentraxin 3 and C-reactive protein as inflammatory markers after a kidney
      transplant.
AB  - OBJECTIVES: There are numerous changes in inflammatory status that occur after a
      kidney transplant. Pentraxin 3 is a marker of inflammation, but little
      information is available about pentraxin 3 levels after a kidney transplant. We
      evaluated the relation between pentraxin 3 and other inflammatory markers
      including high sensitivity C-reactive protein, interleukin 6, and tumor necrosis
      factor alpha in kidney transplant recipients. MATERIALS AND METHODS: Adult
      patients (40 patients; aged, 18-80 y; mean age, 38 +/- 10 y) who had a kidney
      transplant from living-related donors were studied. Patients who had
      comorbidities associated with chronic inflammation were excluded. Blood samples
      were obtained before starting immunosuppressive treatment and 2 months after
      kidney transplant for measurement of pentraxin 3, high sensitivity C-reactive
      protein, interleukin 6, and tumor necrosis factor alpha levels. RESULTS: After
      transplant, mean levels of high sensitivity C-reactive protein and interleukin 6
      decreased but levels of pentraxin 3 and tumor necrosis factor alpha did not
      change. There were significant correlations between interleukin 6 and high
      sensitivity C-reactive protein before transplant (r = 0.71; P <= .0001) and after
      transplant (r = 0.45; P <= .003). There was no correlation between tumor necrosis
      factor alpha and high sensitivity C-reactive protein before transplant, but there
      was a significant correlation between tumor necrosis factor alpha and high
      sensitivity C-reactive protein after transplant (r = 0.36; P <= .03). There was
      no correlation between interleukin 6 and pentraxin 3, tumor necrosis factor alpha
      and pentraxin 3, or high sensitivity C-reactive protein and pentraxin 3 before or
      after transplant. CONCLUSIONS: After a kidney transplant, pentraxin 3 may not be
      useful in determining inflammatory status, and high sensitivity C-reactive
      protein may be better than pentraxin 3 as a marker of inflammation.

PMID- 24568624
TI  - Perspectives on tissue-engineered nerve regeneration for the treatment of spinal
      cord injury.
AB  - Over the past few decades, substantial progress has been made to safely improve
      nerve function in spinal cord injury (SCI) patients through the regeneration of
      injured nerve tissue. This perspective focuses on an extensive overview of SCI
      research as well as tissue-engineered nerve regeneration for the treatment of
      SCI. 

PMID- 24568625
TI  - Simultaneous aptasensor for multiplex pathogenic bacteria detection based on
      multicolor upconversion nanoparticles labels.
AB  - A highly sensitive and specific multiplex method for the simultaneous detection
      of three pathogenic bacteria was fabricated using multicolor upconversion
      nanoparticles (UCNPs) as luminescence labels coupled with aptamers as the
      molecular recognition elements. Multicolor UCNPs were synthesized via doping with
      various rare-earth ions to obtain well-separated emission peaks. The aptamer
      sequences were selected using the systematic evolution of ligands by exponential
      enrichment (SELEX) strategy for Staphylococcus aureus, Vibrio parahemolyticus,
      and Salmonella typhimurium. When applied in this method, aptamers can be used for
      the specific recognition of the bacteria from complex mixtures, including those
      found in real food matrixes. Aptamers and multicolor UCNPs were employed to
      selectively capture and simultaneously quantify the three target bacteria on the
      basis of the independent peaks. Under optimal conditions, the correlation between
      the concentration of three bacteria and the luminescence signal was found to be
      linear from 50-10(6) cfu mL(-1). Improved by the magnetic separation and
      concentration effect of Fe3O4 magnetic nanoparticles, the limits of detection of
      the developed method were found to be 25, 10, and 15 cfu mL(-1) for S. aureus, V.
      parahemolyticus, and S. typhimurium, respectively. The capability of the bioassay
      in real food samples was also investigated, and the results were consistent with
      experimental results obtained from plate-counting methods. This proposed method
      for the detection of various pathogenic bacteria based on multicolor UCNPs has
      great potential in the application of food safety and multiplex nanosensors. 

PMID- 24568627
TI  - Challenges of imaging for cancer in patients with diabetes and obesity.
AB  - A growing body of evidence supports a connection among diabetes (predominantly
      type 2), obesity, and cancer. Multiple meta-analyses of epidemiological data show
      that people with diabetes are at increased risk of developing a variety of
      different cancers and suffer from an increased rate of perioperative
      complications and cancer mortality. Computed tomography (CT) has played an
      important role in diagnosis and staging of cancer. Positron emission tomography
      is complementary to CT in the diagnosis, staging, and evaluation of treatment
      response for many types of cancer. Because of generally poor clinical outcome of
      cancers when they are detected in late stages, more research is now focused on
      stratifying risk to allow personalized screening of at-risk patients and cancer
      detection at an earlier stage. In this review, we summarize basic noninvasive
      imaging techniques currently in use to detect cancer with emphasis on the
      challenges of imaging for early cancer detection in obese patients with diabetes.

PMID- 24568626
TI  - Intradimer/Intermolecular interactions suggest autoinhibition mechanism in
      endophilin A1.
AB  - Endophilin A1 is a homodimeric membrane-binding endocytic accessory protein with
      a high dimerization affinity. Its function has been hypothesized to involve
      autoinhibition. However, the autoinhibition mechanism, as well as the
      physicochemical basis for the high dimerization affinity of endophilin in
      solution, have remained unclear. In this contribution, we use a Forster resonance
      energy transfer (FRET) method to investigate the homodimerization mechanism and
      intradimer molecular interactions in endophilin. For the endophilin N-BAR domain
      (which lacks the SH3 domain including a linker region of the full length
      protein), we observe a large temperature dependence of the dimerization affinity
      and dimer dissociation kinetics, implying large dimerization enthalpy and
      dissociation activation enthalpy, respectively. Our evaluation of the protein
      concentration dependence of dimer dissociation kinetics implies that endophilin
      reversibly forms monomers via a dissociation/reassociation mechanism.
      Furthermore, we use a kinetic method that allows us to compare the dissociation
      kinetics of full-length endophilin to that of truncated mutants. We find that
      mutants that lack either H0 helix or SH3 domain show significantly faster
      dissociation kinetics relative to full-length endophilin. This observation
      supports the presence of an intradimer, intermonomer cross-interaction between H0
      helix and SH3 domain from different subunits within a homodimer. Because the H0
      helix is known to play a significant role in endophilin's membrane interactions,
      our measurements support a syngergistic model where these interactions are
      inhibited in the absence of SH3 domain binding ligands such as dynamin's prolin
      rich domains, and where the binding of these ligands may be suppressed for non
      membrane-bound endophilin. 

PMID- 24568628
TI  - Mapping the 25-item National Eye Institute Visual Functioning Questionnaire (NEI
      VFQ-25) to EQ-5D utility scores.
AB  - PURPOSE: To develop a mapping algorithm for the estimation of EQ-5D-based utility
      scores from observed 25-item National Eye Institute Visual Functioning
      Questionnaire (NEI VFQ-25) scores, a disease-specific, patient-reported outcome
      measure used in several retinal disorders to evaluate vision-specific
      functioning. METHODS: The dataset comprised 951 paired EQ-5D/NEI VFQ-25
      observations from 344 patients in RESTORE, a 12-month, randomized, double-blind
      trial in individuals with visual impairment due to diabetic macular edema. EQ-5D
      index scores (utilities) were calculated based on the UK tariff. We evaluated 11
      models using predictor sets based on the NEI VFQ-25 subscales to estimate utility
      as a function of NEI VFQ-25 score, based on four modeling techniques. Model
      performance was assessed by 10-fold cross-validation comparing root mean squared
      error (RMSE), mean absolute error (MAE) and correlation with EQ-5D score (Pearson
      and Spearman correlation coefficients). RESULTS: Mapping results were similar
      across all techniques and predictor sets. The reverse two-part generalized
      estimating equation model used fewest predictors and had the best predictive
      performance (RMSE 0.200, MAE 0.140). Predicted and original EQ-5D values were not
      strongly correlated (squared Spearman correlation coefficient, 0.34).
      CONCLUSIONS: Although mapping disease-specific instruments to EQ-5D utilities is
      a preferred method by some reimbursement bodies, finding an appropriate mapping
      equation is not straightforward. In this study, mapping NEI VFQ-25 scores to EQ
      5D utilities provided low predictive power, independent of the modeling
      methodology applied, suggesting an inability of the EQ-5D to discriminate vision
      related activities, and highlighting that mapping exercises may lead to
      inaccurate utility values that do not represent patients' preferences.

PMID- 24568629
TI  - Polio virus neutralizing antibody dynamics among children in a north-central and
      South-Western Nigeria state.
AB  - Northern Nigeria accounts for the highest number of confirmed wild polio viruses
      globally. Transmission to neighboring countries is worrisome after the country
      failed to meet several deadlines for polio eradication. Most studies on
      neutralizing antibody have focused on the Northeastern and Northwestern regions.
      This study measured polio virus neutralizing antibody levels among children in
      North-central and South-western Nigeria. Children between the ages of 10 months
      and 13 yr were randomly selected from Abanishe-lolu Hospital Ilorin (North
      central) and Oni Memorial and Adeoyo Hospitals in Ibadan (South-west) Nigeria.
      The alpha neutralization method was employed. Herd immunity was 1.4% in Ilorin,
      36.6% in Oni Memorial Hospital, and 49.5% in Adeoyo Hospital. Out of 299 children
      studied, 49 (16.4%) children had no protection against all poliovirus serotypes
      while 100 (33.4%) were fully protected against all three serotypes. Five (7.9%)
      children in Ilorin and 5 (3.4%) children in Oni Memorial Hospital Ibadan had no
      detectable neutralizing antibody. A significant difference was observed (p=0.000)
      when the GMT against poliovirus 1, 2, and 3 was compared. A significant
      proportion of children were not fully protected. Sero-surveillance is recommended
      for effective monitoring of vaccination efforts to guide health policy
      formulators. 

PMID- 24568631
TI  - Design of novel potent antihyperlipidemic agents with antioxidant/anti
      inflammatory properties: exploiting phenothiazine's strong antioxidant activity.
AB  - Because atherosclerosis is an inflammatory process involving a series of
      pathological events such as dyslipidemia, oxidative stress, and blood clotting
      mechanisms, we hereby report the synthesis and evaluation of novel compounds in
      which antioxidant, anti-inflammatory, and squalene synthase (SQS)
      inhibitory/hypolipidemic activities are combined in simple molecules through
      design. The coupling of two different pharmacophores afforded compounds 1-12,
      whose biological profile was markedly improved compared to those of parent lead
      structures (i.e., the hypolipidemic 2-hydroxy-2-aryl-(benzo)oxa(or thia)zine and
      the antioxidant phenothiazine). Most derivatives strongly inhibited in vitro
      microsomal lipid and LDL peroxidation, exhibiting potent free-radical scavenging
      activity. They further significantly inhibited SQS activity and showed remarkable
      antidyslipidemic activity in vivo in animal models of acute and high-fat-induced
      hyperlipidemia. Finally, several compounds showed anti-inflammatory activity in
      vitro, inhibiting cycloxygenase (COX-1/2) activity. The multimodal properties of
      the new compounds and especially their combined antioxidant/SQS/COX inhibitory
      activity render them interesting lead compounds for further evaluation against
      atherosclerosis. 

PMID- 24568632
TI  - The impact of accreditation of primary healthcare centers: successes, challenges
      and policy implications as perceived by healthcare providers and directors in
      Lebanon.
AB  - BACKGROUND: In 2009, the Lebanese Ministry of Public Health (MOPH) launched the
      Primary Healthcare (PHC) accreditation program to improve quality across the
      continuum of care. The MOPH, with the support of Accreditation Canada, conducted
      the accreditation survey in 25 PHC centers in 2012. This paper aims to gain a
      better understanding of the impact of accreditation on quality of care as
      perceived by PHC staff members and directors; how accreditation affected staff
      and patient satisfaction; key enablers, challenges and strategies to improve
      implementation of accreditation in PHC. METHODS: The study was conducted in 25
      PHC centers using a cross-sectional mixed methods approach; all staff members
      were surveyed using a self-administered questionnaire whereas semi-structured
      interviews were conducted with directors. RESULTS: The scales measuring
      Management and Leadership had the highest mean score followed by Accreditation
      Impact, Human Resource Utilization, and Customer Satisfaction. Regression
      analysis showed that Strategic Quality Planning, Customer Satisfaction and Staff
      Involvement were associated with a perception of higher Quality Results.
      Directors emphasized the benefits of accreditation with regards to documentation,
      reinforcement of quality standards, strengthened relationships between PHC
      centers and multiple stakeholders and improved staff and patient satisfaction.
      Challenges encountered included limited financial resources, poor infrastructure,
      and staff shortages. CONCLUSIONS: To better respond to population health needs,
      accreditation is an important first step towards improving the quality of PHC
      delivery arrangement system. While there is a need to expand the implementation
      of accreditation to cover all PHC centers in Lebanon, considerations should be
      given to strengthening their financial arrangements as well.

PMID- 24568630
TI  - Polysome profiling reveals broad translatome remodeling during endoplasmic
      reticulum (ER) stress in the pathogenic fungus Aspergillus fumigatus.
AB  - BACKGROUND: The unfolded protein response (UPR) is a network of intracellular
      signaling pathways that supports the ability of the secretory pathway to maintain
      a balance between the load of proteins entering the endoplasmic reticulum (ER)
      and the protein folding capacity of the ER lumen. Current evidence indicates that
      several pathogenic fungi rely heavily on this pathway for virulence, but there is
      limited understanding of the mechanisms involved. The best known functional
      output of the UPR is transcriptional upregulation of mRNAs involved in ER
      homeostasis. However, this does not take into account mechanisms of translational
      regulation that involve differential loading of ribosomes onto mRNAs. In this
      study, a global analysis of transcript-specific translational regulation was
      performed in the pathogenic mold Aspergillus fumigatus to determine the nature
      and scope of the translational response to ER stress. RESULTS: ER stress was
      induced by treating the fungus with dithiothreitol, tunicamycin, or a thermal up
      shift. The mRNAs were then fractionated on the basis of ribosome occupancy into
      an under-translated pool (U) and a well-translated pool (W). The mRNAs were used
      to interrogate microarrays and the ratio of the hybridization signal (W/U) was
      used as an indicator of the relative translational efficiency of a mRNA under
      each condition. The largest category of translationally upregulated mRNAs during
      ER stress encoded proteins involved in translation. Components of the ergosterol
      and GPI anchor biosynthetic pathways also showed increased polysome association,
      suggesting an important role for translational regulation in membrane and cell
      wall homeostasis. ER stress induced limited remodeling of the secretory pathway
      translatome. However, a select group of transcription factors was translationally
      upregulated, providing a link to subsequent modification of the transcriptome.
      Finally, we provide evidence that one component of the ER stress translatome is a
      novel mRNA isoform from the yvc1 gene that is induced by ER stress in a UPR
      dependent manner. CONCLUSIONS: Together, these findings define a core set of
      mRNAs subject to translational control during the adaptive response to acute ER
      stress in A. fumigatus and reveal a remarkable breadth of functions that are
      needed to resolve ER stress in this organism.

PMID- 24568633
TI  - Sodium butyrate facilitates reprogramming by derepressing OCT4 transactivity at
      the promoter of embryonic stem cell-specific miR-302/367 cluster.
AB  - Small-molecule inhibitors and microRNAs (miRNAs) are two newly emerging classes
      of tools for optimizing induced pluripotent stem cell (iPSC) generation. We
      report here that sodium butyrate (NaB), a small-molecule inhibitor of histone
      deacetylases (HDACs), upregulates transcriptional levels of the miR-302/367
      cluster by enhancing Oct4 transcriptional activity at the miR-302/367 cluster
      promoter. NaB does not affect the OCT4 DNA-binding domain; instead it enhances
      transactivity of the OCT4 transactivation domains. We elucidate that OCT4
      transcriptional activity is usually dampened by its associated HDACs in cells and
      can be derepressed by NaB by impairing the interaction between Oct4 and HDACs,
      which leads to an elevated expression of the miR-302/367 cluster. Our new
      findings suggest a novel molecular mechanism for NaB in promoting somatic cell
      reprogramming via the miR-302/367 cluster.

PMID- 24568635
TI  - Doping change in the Bi-2212 superconductor directly induced by a hard X-ray
      nanobeam.
AB  - We describe the controlled use of a 17 keV X-ray synchrotron nanobeam to
      progressively change the oxygen doping level in Bi-2212 superconducting whisker
      like single crystals. Our data combine structural and electrical information
      collected on the same crystals, showing a maximum change in the critical
      temperature Tc of 1.3 K and a maximum elongation of ~1 A in the c-axis length,
      compared to the as-grown conditions. Simulations of our experimental conditions
      by means of a finite element model exclude local heating induced by the X-ray
      nanobeam as a possible cause for the change in the doping level and suggest an
      important role of secondary electrons. These findings support the possible use of
      hard X-rays as a novel direct-writing, photoresist-free lithographic process for
      the fabrication of superconducting devices, with potential nanometric resolution
      and 3D capability. 

PMID- 24568634
TI  - Testing previous model predictions against new data on human papillomavirus
      vaccination program outcomes.
AB  - BACKGROUND: Vaccination against human papillomavirus (HPV), predominantly
      targeting young females, has been introduced in many countries. Decisions to
      implement programs, which have involved substantial investment by governments,
      have in part been based on findings from cost-effectiveness models. Now that
      vaccination programs have been in place for some years, it is becoming possible
      to observe their effects, and compare these with model effectiveness predictions
      made previously. FINDINGS: Australia introduced a publicly-funded HPV vaccination
      program in 2007. Recently reported Australian data from a repeat cross-sectional
      survey showed a substantial (77%) fall in HPV16 prevalence in women aged 18-24
      years in 2010-2011, compared to pre-vaccination levels. We have previously
      published model predictions for the population-wide reduction in incident HPV16
      infections post-vaccination in Australia. We compared prior predictions from the
      same model (including the same assumed uptake rates) for the reduction in HPV16
      prevalence in women aged 18-24 years by the end of 2010 with the observed data.
      Based on modelled vaccine uptake which is consistent with recent data on three
      dose uptake (78% at 12-13 years; lower uptake in older catch-up age cohorts), we
      had predicted a 70% reduction in prevalence in 18-24 year old females by the end
      of 2010. Based on modelled vaccine uptake consistent with recent national data
      for two-dose coverage and similar to that reported by women in the cross
      sectional study, we had predicted a 79% reduction. CONCLUSIONS: A close
      correspondence was observed between the prior model predictions and the recently
      reported findings on the rapid drop in HPV prevalence in Australia. Because
      broadly similar effectiveness predictions have been reported from other models
      used for cost-effectiveness predictions, this provides reassurance that the
      substantial public investment in HPV vaccination has been grounded in valid
      estimates of the effects of vaccination.

PMID- 24568637
TI  - Characterization of unknown brominated disinfection byproducts during
      chlorination using ultrahigh resolution mass spectrometry.
AB  - Brominated disinfection byproducts (Br-DBPs), formed from the reaction of
      disinfectant(s) with natural organic matter in the presence of bromide in raw
      water, are generally more cytotoxic and genotoxic than their chlorinated
      analogues. To date, only a few Br-DBPs in drinking water have been identified,
      while a significant portion of Br-DBPs in drinking water is still unknown. In
      this study, negative ion electrospray ionization ultrahigh resolution Fourier
      transform ion cyclotron resonance mass spectrometry (ESI FT-ICR MS) was used to
      characterize unknown Br-DBPs in artificial drinking water. In total, 441 formulas
      for one-bromine-containing products and 37 formulas for two-bromine-containing
      products, most of which had not been previously reported, were detected in the
      chlorinated sample. Most Br-DBPs have corresponding chlorine-containing analogues
      with identical CHO composition. In addition, on-resonance collision-induced
      dissociation (CID) of single ultrahigh resolved bromine containing mass peaks was
      performed in the ICR cell to isolate single bromine-containing components in a
      very complex natural organic matter spectrum and provide structure information.
      Relatively abundant neutral loss of CO2 was observed in MS-MS spectra, indicating
      that the unknown Br-DBPs are rich in carboxyl groups. The results demonstrate
      that the ESI FT-ICR MS method could provide valuable molecular composition and
      structure information on unknown Br-DBPs. 

PMID- 24568638
TI  - Colloidal crystal formation at the "Nafion-water" interface.
AB  - In our recent work [Bunkin et al. Water 2013, 4, 129-154] it was first obtained
      that the water layer, having a size of several tens of micrometers and being
      adjacent to the swollen Nafion interface, is characterized by enhanced optical
      density; the refractive index of water at the interface is 1.46. Furthermore, the
      birefringence effect was observed in this layer. To explain these results, it has
      been hypothesized that because of "disentangling" of charged polymer chains from
      the Nafion surface toward the bulk of water, a photonic crystal close to the
      surface is formed [Bunkin et al. Water 2013, 4, 129-154]. In this paper, we
      describe experiments with laser-stimulated luminescence from dry and swollen
      Nafion. It was shown in the experiment with dry Nafion that the apparatus
      function of our experimental setup (Green's function) is well-described by a
      Gaussian profile. It was obtained that a highly concentrated colloidal suspension
      of Nafion particles with a steep spatial boundary is formed in the water layer
      adjacent to the interface. The volume density of the Nafion particles as a
      function of the distance from the Nafion interface was found. These findings can
      be considered indirect confirmation of the previously formulated photonic crystal
      hypothesis [Bunkin et al. Water 2013, 4, 129-154].

PMID- 24568636
TI  - Forced swim test induces divergent global transcriptomic alterations in the
      hippocampus of high versus low novelty-seeker rats.
AB  - BACKGROUND: Many neuropsychiatric disorders, including stress-related mood
      disorders, are complex multi-parametric syndromes. Susceptibility to stress and
      depression is individually different. The best animal model of individual
      differences that can be used to study the neurobiology of affect regards
      spontaneous reactions to novelty. Experimentally, when naive rats are exposed to
      the stress of a novel environment, they display a highly variable exploratory
      activity and are classified as high or low responders (HR or LR, respectively).
      Importantly, HR and LR rats do not seem to exhibit a substantial differentiation
      in relation to their 'depressive-like' status in the forced swim test (FST), a
      widely used animal model of 'behavioral despair'. In the present study, we
      investigated whether FST exposure would be accompanied by phenotype-dependent
      differences in hippocampal gene expression in HR and LR rats. RESULTS: HR and LR
      rats present a distinct behavioral pattern in the pre-test session but develop
      comparable depressive-like status in the second FST session. At 24 h following
      the second FST session, HR and LR rats (stressed and unstressed controls) were
      sacrificed and hippocampal samples were independently analyzed on whole rat
      genome Illumina arrays. Functional analysis into pathways and networks was
      performed using Ingenuity Pathway Analysis (IPA) software. Notably, hippocampal
      gene expression signatures between HR and LR rats were markedly divergent,
      despite their comparable depressive-like status in the FST. These molecular
      differences are reflected in both the extent of transcriptional remodeling
      (number of significantly changed genes) and the types of molecular pathways
      affected following FST exposure. A markedly higher number of genes (i.e., 2.28
      fold) were statistically significantly changed following FST in LR rats, as
      compared to their HR counterparts. Notably, genes associated with neurogenesis
      and synaptic plasticity were induced in the hippocampus of LR rats in response to
      FST, whereas in HR rats, FST induced pathways directly or indirectly associated
      with induction of apoptotic mechanisms. CONCLUSIONS: The markedly divergent gene
      expression signatures exposed herein support the notion that the hippocampus of
      HR and LR rats undergoes distinct transcriptional remodeling in response to the
      same stress regimen, thus yielding a different FST-related 'endophenotype',
      despite the seemingly similar depressive-like phenotype.

PMID- 24568639
TI  - Investigating C-4 sugar contamination of manuka honey and other New Zealand honey
      varieties using carbon isotopes.
AB  - Carbon isotopes (delta(13)C honey and delta(13)C protein) and apparent C-4 sugar
      contents of 1023 New Zealand honeys from 15 different floral types were analyzed
      to investigate which New Zealand honey is prone to failing the AOAC 998.12 C-4
      sugar test and evaluate the occurrence of false-positive results. Of the 333
      honey samples that exceeded the 7% C-4 sugar threshold, 324 samples of these were
      New Zealand manuka honey (Leptospermum scoparium, 97.2% of all fails found in the
      study). Three monofloral honeys (ling, kamahi, and tawari) had nine samples (2.8%
      of all fails found in the study) with apparent C-4 sugars exceeding 7%. All other
      floral types analyzed did not display C-4 sugar fails. False-positive results
      were found to occur for higher activity New Zealand manuka honey with a
      methylglyoxal content >250 mg/kg or a nonperoxide activity >10+, and for some
      ling, kamahi and tawari honeys. Recommendations for future interpretation of the
      AOAC 998.12 C-4 sugar method are proposed. 

PMID- 24568640
TI  - How cellulose stretches: synergism between covalent and hydrogen bonding.
AB  - Cellulose is the most familiar and most abundant strong biopolymer, but the
      reasons for its outstanding mechanical performance are not well understood. Each
      glucose unit in a cellulose chain is joined to the next by a covalent C-O-C
      linkage flanked by two hydrogen bonds. This geometry suggests some form of
      cooperativity between covalent and hydrogen bonding. Using infrared spectroscopy
      and X-ray diffraction, we show that mechanical tension straightens out the zigzag
      conformation of the cellulose chain, with each glucose unit pivoting around a
      fulcrum at either end. Straightening the chain leads to a small increase in its
      length and is resisted by one of the flanking hydrogen bonds. This constitutes a
      simple form of molecular leverage with the covalent structure providing the
      fulcrum and gives the hydrogen bond an unexpectedly amplified effect on the
      tensile stiffness of the chain. The principle of molecular leverage can be
      directly applied to certain other carbohydrate polymers, including the animal
      polysaccharide chitin. Related but more complex effects are possible in some
      proteins and nucleic acids. The stiffening of cellulose by this mechanism is,
      however, in complete contrast to the way in which hydrogen bonding provides
      toughness combined with extensibility in protein materials like spider silk. 

PMID- 24568641
TI  - Progress in prevention of mother-to-child transmission of HIV-1 in Zhejiang
      province, China, 2007-2013.
AB  - This is a retrospective study based on surveillance of Human Immunodeficiency
      Virus type-1 (HIV-1) positive pregnant women and their children in China's
      Zhejiang Province. HIV counseling and testing, mother and infant characteristics,
      and outcomes are reported here. This study compares two principal periods, the
      period from 2007-2009 and the period from 2010 to 2013. The average rate of HIV
      counseling among pregnant women rose from 84.87% during the earlier period to
      99.08% during the latter period. And the rate of HIV testing also rose
      significantly, from 80.60% to 98.58%. The HIV-1 prevalence among pregnant women
      increased slightly, from 0.01% to 0.02%. Over 70% of infected women were
      migrants. Half of these HIV-1 positive pregnant women were 20-30 years old.
      Significant differences in the characteristics of HIV-1 positive pregnant women
      were observed with time. The proportion of women who were employed increased
      dramatically from an average of 15.03% during 2007-2009 to an average of 31.34%
      during 2010-2013 and the proportion of women who had completed high school
      education increased from 0.52% to 6.51%. During 2007-2009, an average of 3.11% of
      these women was diagnosed before their pregnancies. During 2010-2013, this
      average reached to 32.53%. Sexual contact remained the primary route of
      transmission route during both periods, accounting for half of the infections.
      The proportion of women who had acquired HIV by blood transfusion declined
      noticeably. The proportion of mothers and children with antiretroviral therapy
      increased considerably over time. The overall mother-to-child transmission rate
      was found to be 7.14%. Although some progress has been made, further work should
      be performed, fostering early identification and timely therapy. Particular
      attention should be paid to health care of migrants. 

PMID- 24568643
TI  - Current status of multipotent mesenchymal stromal cells.

PMID- 24568642
TI  - The association between sleep disturbances and suicidal behaviors in patients
      with psychiatric diagnoses: a systematic review and meta-analysis.
AB  - BACKGROUND: Identifying patients with increased risk of suicidal behaviors is a
      constant challenge and concern for clinicians caring for patients with
      psychiatric conditions. We conducted a systematic review to assess the
      association between suicidal behaviors and sleep disturbances in psychiatric
      patients. METHODS: A systematic literature search of Ovid Medline In-Process &
      Other Non-Indexed Citations, Ovid MEDLINE, Ovid EMBASE, Ovid PsycInfo, Ovid
      Cochrane Database of Systematic Reviews, Ovid Cochrane Central Register of
      Controlled Trials, and Scopus was conducted using earliest inclusive dates to 28
      June 2013. Eligible studies were comparative observational studies that reported
      sleep disturbances in psychiatric patients and the outcome of interest (any type
      of suicidal behaviors). Pairs of reviewers extracted descriptive data, study
      quality, and outcomes. Odds ratios (OR) and 95% confidence intervals (CI) were
      pooled across studies using the random-effects model. Newcastle-Ottawa scale was
      used to critically appraise study quality. RESULTS: Nineteen studies met the
      inclusion criteria. Compared to those without sleep disturbances, patients with
      psychiatric diagnoses and co-morbid sleep disturbances were significantly more
      likely to report suicidal behaviors (OR = 1.99, 95% CI 1.72, 2.30, P <0.001). The
      association was also demonstrated across several psychiatric conditions including
      depression (OR = 3.05, 95% CI 2.07, 4.48, P <0.001), post-traumatic stress
      disorder (PTSD) (OR = 2.56, 95% CI 1.91, 3.43, P <0.001), panic disorder (OR =
      3.22, 95% CI 1.09, 9.45, P = 0.03), and schizophrenia (OR = 12.66, 95% CI 1.40,
      114.44, P = 0.02). In subgroup analysis based on the type of sleep disorder, we
      also found suicidal behavior to be significantly associated with the presence of
      insomnia, parasomnias, and sleep-related breathing disorders, but not
      hypersomnias. CONCLUSIONS: This systematic review and meta-analysis suggests that
      in patients with psychiatric diagnoses, sleep disturbances are associated with
      the increased risk of suicidal behaviors.

PMID- 24568644
TI  - Myasthenic crisis after a renal transplant successfully treated with intravenous
      immunoglobulin.
AB  - Myasthenia gravis is an autoimmune disease characterized by muscle weakness.
      Myasthenic crisis is a life-threatening complication of myasthenia gravis
      precipitated by several factors. We experienced a myasthenic crisis after a
      deceased-donor kidney transplant in a 35-year-old woman who already had been
      diagnosed with myasthenia gravis. She received mechanical ventilatory support and
      intravenous immunoglobulin for treatment of the myasthenic crisis. During the
      early posttransplant period, she recovered with immediate graft function, and her
      graft functioning did not deteriorate during the myasthenic crisis. We suggest
      that physicians be aware of worsening of myasthenia gravis when patients with
      myasthenia gravis undergo a kidney transplant. 

PMID- 24568645
TI  - Detection of pH change in cytoplasm of live myocardial ischemia cells via the
      ssDNA-SWCNTs nanoprobes.
AB  - Myocardial ischemia is featured by a significant increase in the cytoplasm proton
      concentration, and such a proton change may be applied as an index for earlier
      ischemic heart disease diagnostics. But such a pH change in a live heart cell is
      difficult to monitor as a normal fluorescent probe cannot specifically transport
      into the cytoplasm of an ischemic cell. This is because the heart cell contains
      condensed myofibrils which are tight barriers for a normal probe to penetrate. We
      design fluorescent probes, single-strand DNA wrapped single-wall carbon nanotubes
      (ssDNA-SWCNTs), where the ssDNA is labeled by the dye molecule hexachloro-6
      carboxyfluorescein (HEX). This nanoprobe could transport well into a live heart
      cell and locate in the cytoplasm to sensitively detect the intracellular pH
      change of myocardial ischemia. Briefly, protons neutralize the negative charges
      of nanoprobes in the cytoplasm. This will weaken the stability of nanoprobes and
      further tune their aggregation. Such aggregations induce the HEX of some
      nanoprobes condensed together and further result in their fluorescence quenching.
      The nanoprobes are advantaged in penetrating condensed myofibrils of the heart
      cell, and their fluorescence intensity is sensitive to the proton concentration
      change in the live cell cytoplasm. This new method may provide great assistance
      in earlier cardiopathy diagnosis in the future. 

PMID- 24568647
TI  - Hospital strategies under the "quasi" global budget payment system.

PMID- 24568646
TI  - Complex RNA folding kinetics revealed by single-molecule FRET and hidden Markov
      models.
AB  - We have developed a hidden Markov model and optimization procedure for photon
      based single-molecule FRET data, which takes into account the trace-dependent
      background intensities. This analysis technique reveals an unprecedented amount
      of detail in the folding kinetics of the Diels-Alderase ribozyme. We find a
      multitude of extended (low-FRET) and compact (high-FRET) states. Five states were
      consistently and independently identified in two FRET constructs and at three
      Mg(2+) concentrations. Structures generally tend to become more compact upon
      addition of Mg(2+). Some compact structures are observed to significantly depend
      on Mg(2+) concentration, suggesting a tertiary fold stabilized by Mg(2+) ions.
      One compact structure was observed to be Mg(2+)-independent, consistent with
      stabilization by tertiary Watson-Crick base pairing found in the folded Diels
      Alderase structure. A hierarchy of time scales was discovered, including dynamics
      of 10 ms or faster, likely due to tertiary structure fluctuations, and slow
      dynamics on the seconds time scale, presumably associated with significant
      changes in secondary structure. The folding pathways proceed through a series of
      intermediate secondary structures. There exist both compact pathways and more
      complex ones, which display tertiary unfolding, then secondary refolding, and,
      subsequently, again tertiary refolding. 

PMID- 24568648
TI  - Association between the FAS rs2234767G/A polymorphism and cancer risk: a
      systematic review and meta-analysis.
AB  - Abnormal regulation of apoptosis can lead to carcinogenesis. Single nucleotide
      polymorphisms in apoptotic genes have been associated with cancer risk, such as
      the FAS rs2234767G/A polymorphism, which alters transcription of the FAS
      promoter. Downregulation of FAS, with resultant cellular resistance to death
      signals, has been found in many cancers. However, the association between the FAS
      rs2234767G/A polymorphism and cancer risk is still controversial. Here, we
      performed a meta-analysis including 41 articles (44 case-control studies, 17,814
      cases and 24,307 controls) identified from PubMed and Chinese language (CNKI and
      WanFang) databases related to cancer susceptibility and the FAS rs2234767G/A
      polymorphism. We used odds ratios (ORs) and 95% confidence intervals (CIs) to
      assess the strength of the associations. We found that the rs2234767 G-allele was
      a protective factor for cancer risk (GG vs. AA: OR=0.88, 95% CI=0.79-0.98; GG+GA
      vs. AA: OR=0.87, 95% CI=0.79-0.96). Similar associations were detected in the
      "source of control", ethnicity, and cancer type subgroups. Further studies on a
      larger sample size and considering gene-environment interactions should be
      conducted to confirm the role of FAS polymorphisms, especially rs2234767G/A, in
      cancer risk. 

PMID- 24568649
TI  - Generation and characterization of chicken-sourced single-chain variable
      fragments (scFvs) against porcine interferon-gamma (pIFN-gamma).
AB  - Development of chicken-sourced antibodies offers an alternative strategy for the
      development of highly specific antibodies against mammalian proteins with
      conserved epitopes due to the phylogenetic distance between avian and mammalian
      species. In this study, the single-chain variable fragments (scFvs) against
      porcine interferon-gamma was screened and characterized from a hyperimmunized
      chicken phage display library. The expressed soluble scFvs exhibited highly
      specific recognition of porcine interferon-gamma in ELISA, Western blot, and
      immunofluorescence staining assays. Results of the current study indicate that it
      is possible to develop scFv IgY antibodies to a mammalian interferon by using
      Biopanning technology. Furthermore, it also confirms that monoclonal avian IgY
      antibody technique could be applied as a promising tool to produce immunoglobulin
      molecules with high specificity and affinity towards conserved mammalian epitopes
      or antigens. 

PMID- 24568650
TI  - Antimicrobial susceptibility of Streptococcus pneumoniae in adult patients with
      pneumococcal pneumonia in an urban hospital in Mozambique.
AB  - BACKGROUND: Streptococcus pneumoniae is the leading cause of community-acquired
      pneumonia in Africa. Antimicrobial resistance of S. pneumoniae to penicillin and
      other commonly used antibiotics has increased worldwide. However, prevalence data
      from the African region are sparse, especially with regard to adults. FINDINGS:
      In this study, adult patients presenting at an urban referral hospital in central
      Mozambique were screened for pneumococcal pneumonia during an 8-week period in
      2010: Patients with a respiratory syndrome underwent chest radiography and a
      sputum sample was collected for pneumococcal culture and antimicrobial
      susceptibility testing. A urine sample was tested for the presence of
      pneumococcal antigen.177 patients with a respiratory syndrome were included.
      Overall, 41/177 (23%) patients fulfilled criteria for definite or probable
      pneumococcal pneumonia and in the group of patients with a positive chest x-ray
      this concerned 35/86 (41%) patients. 166 sputum cultures yielded 16 pneumococcal
      strains. One mg oxacillin disc testing identified potential penicillin resistance
      in 7/16 (44%) strains. Penicillin minimal inhibitory concentrations (MICs) were
      measured for 15 of these strains and ranged from <0.016-0.75 mg/L. No MICs >2
      mg/L were found, but 3/15 (20%) pneumococcal strains had MICs >0.5 mg/L. All
      pneumococci were sensitive to erythromycin as measured by disc diffusion testing,
      whereas 44% was resistant to trimethoprim-sulfametoxazole. CONCLUSIONS: The
      proportion of pneumonia cases attributable to pneumococcus appeared to be high.
      Whilst none of the S. pneumoniae strains tested were penicillin resistant,
      standard penicillin dosing for pneumonia may be insufficient given the observed
      range of pneumococcal penicillin MICs.

PMID- 24568652
TI  - The feasibility of a physical activity referral network for pediatric obesity.
AB  - BACKGROUND: Pediatricians cite a lack of physical activity referral (PAR)
      opportunities as a major barrier to treating obesity. However, no literature
      exists on PARs for youth in the clinical setting. This study explores the
      feasibility of implementing PARs in a pediatric obesity clinic. METHODS: Patients
      ages 6-18 years in an obesity clinic from July 2010 to October 2011 were referred
      to PARs in their community. Researchers confirmed enrollment and participation in
      activities by follow-up phone calls. RESULTS: Of 130 eligible youth, 102 (78%)
      agreed to be referred to a physical activity program; 45 (35%) enrolled and 35
      (27%) reported actually participating in an activity, for an average of 1.4 hours
      per week. Youth participated in 9 of 69 available activity programs included in
      the PAR network. Patient characteristics at baseline did not predict
      participation in an activity. Youth referred to organizations that contacted
      interested families were 5 times as likely to enroll in activities as youth
      referred to organizations that did not contact families (p < 0.001). CONCLUSION:
      Although only 27% of eligible youth participated in an activity through the PAR
      network, exposing 1 in 4 obese youth to 1.4 hours of physical activity weekly
      could have a significant public health impact. These results suggest that PAR
      networks for overweight and obese youth should focus on organizations that have
      the infrastructure to contact youth and their families, and that a small number
      of physical activity programs could form the basis for launching PAR networks.

PMID- 24568651
TI  - Functional genomics reveals that Clostridium difficile Spo0A coordinates
      sporulation, virulence and metabolism.
AB  - BACKGROUND: Clostridium difficile is an anaerobic, Gram-positive bacterium that
      can reside as a commensal within the intestinal microbiota of healthy individuals
      or cause life-threatening antibiotic-associated diarrhea in immunocompromised
      hosts. C. difficile can also form highly resistant spores that are excreted
      facilitating host-to-host transmission. The C. difficile spo0A gene encodes a
      highly conserved transcriptional regulator of sporulation that is required for
      relapsing disease and transmission in mice. RESULTS: Here we describe a genome
      wide approach using a combined transcriptomic and proteomic analysis to identify
      Spo0A regulated genes. Our results validate Spo0A as a positive regulator of
      putative and novel sporulation genes as well as components of the mature spore
      proteome. We also show that Spo0A regulates a number of virulence-associated
      factors such as flagella and metabolic pathways including glucose fermentation
      leading to butyrate production. CONCLUSIONS: The C. difficile spo0A gene is a
      global transcriptional regulator that controls diverse sporulation, virulence and
      metabolic phenotypes coordinating pathogen adaptation to a wide range of host
      interactions. Additionally, the rich breadth of functional data allowed us to
      significantly update the annotation of the C. difficile 630 reference genome
      which will facilitate basic and applied research on this emerging pathogen.

PMID- 24568653
TI  - Effects of short-term ingestion of Russian Tarragon prior to creatine monohydrate
      supplementation on whole body and muscle creatine retention and anaerobic sprint
      capacity: a preliminary investigation.
AB  - BACKGROUND: Extracts of Russian Tarragon (RT) have been reported to produce anti
      hyperglycemic effects and influence plasma creatine (Cr) levels while
      supplementing with creatine monohydrate (CrM). The purpose of this preliminary
      study was to determine if short-term, low-dose aqueous RT extract ingestion prior
      to CrM supplementation influences whole body Cr retention, muscle Cr or measures
      of anaerobic sprint performance. METHODS: In a double-blind, randomized, and
      crossover manner; 10 recreationally trained males (20 +/- 2 yrs; 179 +/- 9 cm;
      91.3 +/- 34 kg) ingested 500 mg of aqueous RT extract (Finzelberg, Andernach,
      Germany) or 500 mg placebo 30-minutes prior to ingesting 5 g of CrM (Creapure(r),
      AlzChem AG, Germany) twice per day for 5-days then repeated after a 6-week wash
      out period. Urine was collected at baseline and during each of the 5-days of
      supplementation to determine urine Cr content. Whole body Cr retention was
      estimated from urine samples. Muscle biopsies were obtained for determination of
      muscle free Cr content. Participants also performed two 30-second Wingate
      anaerobic capacity tests prior to and following supplementation for determination
      of peak power (PP), mean power (MP), and total work (TW). Data were analysed by
      repeated measures MANOVA. RESULTS: Whole body daily Cr retention increased in
      both groups following supplementation (0.0 +/- 0.0; 8.2 +/- 1.4, 6.5 +/- 2.4, 5.6
      +/- 3.2, 6.1 +/- 2.6, 4.8 +/- 3.2 g . d-1; p = 0.001) with no differences
      observed between groups (p = 0.59). After 3 and 5-days of supplementation,
      respectively, both supplementation protocols demonstrated a significant increase
      in muscle free Cr content from baseline (4.8 +/- 16.7, 15.5 +/- 23.6 mmol . kg-1
      DW, p = 0.01) with no significant differences observed between groups (p = 0.34).
      Absolute change in MP (9 +/- 57, 35 +/- 57 W; p = 0.031), percent change in MP
      (2.5 +/- 10.5, 6.7 +/- 10.4%; p = 0.026), absolute change in TW (275 +/- 1,700,
      1,031 +/- 1,721 J; p = 0.032), and percent change in TW (2.5 +/- 10.5, 6.6 +/-
      10.4%; p = 0.027) increased over time in both groups with no differences observed
      between groups. CONCLUSIONS: Short-term CrM supplementation (10 g . d-1 for 5
      days) significantly increased whole body Cr retention and muscle free Cr content.
      However, ingesting 500 mg of RT 30-min prior to CrM supplementation did not
      affect whole body Cr retention, muscle free Cr content, or anaerobic sprint
      capacity in comparison to ingesting CrM with a placebo.

PMID- 24568656
TI  - MoS2 P-type transistors and diodes enabled by high work function MoOx contacts.
AB  - The development of low-resistance source/drain contacts to transition-metal
      dichalcogenides (TMDCs) is crucial for the realization of high-performance logic
      components. In particular, efficient hole contacts are required for the
      fabrication of p-type transistors with MoS2, a model TMDC. Previous studies have
      shown that the Fermi level of elemental metals is pinned close to the conduction
      band of MoS2, thus resulting in large Schottky barrier heights for holes with
      limited hole injection from the contacts. Here, we show that substoichiometric
      molybdenum trioxide (MoOx, x < 3), a high work function material, acts as an
      efficient hole injection layer to MoS2 and WSe2. In particular, we demonstrate
      MoS2 p-type field-effect transistors and diodes by using MoOx contacts. We also
      show drastic on-current improvement for p-type WSe2 FETs with MoOx contacts over
      devices made with Pd contacts, which is the prototypical metal used for hole
      injection. The work presents an important advance in contact engineering of TMDCs
      and will enable future exploration of their performance limits and intrinsic
      transport properties. 

PMID- 24568654
TI  - Abuse and resilience in relation to HAART medication adherence and HIV viral load
      among women with HIV in the United States.
AB  - Abuse is highly prevalent among HIV+ women, leading to behaviors, including lower
      adherence to highly active antiretroviral therapy (HAART) that result in poor
      health outcomes. Resilience (functioning competently despite adversity) may
      buffer the negative effects of abuse. This study investigated how resilience
      interacted with abuse history in relation to HAART adherence, HIV viral load
      (VL), and CD4+ cell count among a convenience sample of 138 HIV+ women from the
      Ruth M. Rothstein CORE Center/Cook County Health and Hospital Systems site of the
      Women's Interagency HIV Study (WIHS). Resilience was measured by the 10-item
      Connor-Davidson Resilience Scale (CD-RISC). HAART adherence (>=95% vs. <95% self
      reported usage of prescribed medication) and current or prior sexual, physical,
      or emotional/domestic abuse, were reported during structured interviews. HIV
      viral load (>=20 vs. <20 copies/mL) and CD4+ count (200 vs. <200 cells/mm) were
      measured with blood specimens. Multiple logistic regressions, controlling for
      age, race, income, enrollment wave, substance use, and depressive symptoms,
      indicated that each unit increase in resilience was significantly associated with
      an increase in the odds of having >=95% HAART adherence and a decrease in the
      odds of having a detectable viral load. Resilience-Abuse interactions showed that
      only among HIV+ women with sexual abuse or multiple abuses did resilience
      significantly relate to an increase in the odds of >=95% HAART adherence.
      Interventions to improve coping strategies that promote resilience among HIV+
      women may be beneficial for achieving higher HAART adherence and viral
      suppression.

PMID- 24568655
TI  - Impact of ethnic-specific guidelines for anti-hypertensive prescribing in primary
      care in England: a longitudinal study.
AB  - BACKGROUND: In England, the National Institute for Health and Care Excellence
      (NICE) produces guidelines for the management of hypertension. In 2006, the NICE
      guidelines introduced an ethnic-age group algorithm based on the 2004 British
      Hypertension Society guidelines to guide antihypertensive drug prescription.
      METHODS: A longitudinal retrospective study with 15933 hypertensive patients aged
      18 years or over and registered with 28 general practices in Wandsworth, London
      in 2007 was conducted to assess variations in antihypertensive prescribing.
      Logistic models were used to measure variations in the odds of being prescribed
      the 2006 NICE first line recommended monotherapy among NICE patient groups over
      the period. RESULTS: From 2000 to 2007, the percentage of patients prescribed the
      recommended monotherapy increased from 54.2% to 61.4% (p < 0.0001 for annual
      trend). Over the study period, black patients were more likely to be prescribed
      the recommended monotherapy than younger non-black patients (OR 0.16, 95% CI 0.12
      0.21) and older non-black patients (OR 0.49, 95% CI 0.37-0.65). After the
      introduction of the NICE guidelines there was an increase in the NICE recommended
      monotherapy (OR 1.44, 95% CI 1.19-1.75) compared with the underlying trend.
      Compared to black patients, an increase in the use of recommended monotherapy was
      observed in younger non-black patients (OR 1.49, 95% CI 1.17-1.91) but not in
      older non-black patients (OR 0.58, 95% CI 0.46-0.74). CONCLUSION: The
      introduction of the 2006 NICE guideline had the greatest impact on prescribing
      for younger non-black patients. Lower associated increases among black patients
      may be due to their higher levels of recommended prescribing at baseline. The
      analysis suggests that guidelines did not impact equally on all patient groups.

PMID- 24568658
TI  - Thermodynamics of phase coexistence and metal-nonmetal transition in mercury:
      assessment of effective potentials via expanded Wang-Landau simulations.
AB  - We present molecular simulation results on the thermodynamics of phase
      transitions (specifically, the vapor-liquid and metal-nonmetal transitions) in
      mercury, as predicted by effective potential models. We use a recently developed
      method, known as Expanded Wang-Landau simulations, to determine the grand
      canonical partition function of systems of mercury atoms. Using the statistical
      mechanics formalism, we are then able to determine all thermodynamic properties
      of the system, including the Gibbs free energy and entropy. Prior experimental
      and theoretical work has emphasized the strong interplay between the vapor-liquid
      coexistence and the metal-nonmetal transition. We therefore start by assessing
      the accuracy of the effective potentials considered in this work through a
      comparison to the available experimental data. We then analyze the thermodynamics
      of the nonmetal liquid-metal liquid transition, characterized by sharp variations
      in the rate of change of Gibbs free energy and enthalpy as a function of density.
      We also identify a crossover density (10.5 g/cm(3)) consistent with the results
      of recent ab initio calculations and with the experiment. 

PMID- 24568657
TI  - Propargyl-linked antifolates are dual inhibitors of Candida albicans and Candida
      glabrata.
AB  - Species of Candida, primarily C. albicans and with increasing prevalence, C.
      glabrata, are responsible for the majority of fungal bloodstream infections that
      cause morbidity, especially among immune compromised patients. While the
      development of new antifungal agents that target the essential enzyme,
      dihydrofolate reductase (DHFR), in both Candida species would be ideal, previous
      attempts have resulted in antifolates that exhibit inconsistencies between enzyme
      inhibition and antifungal properties. In this article, we describe the evaluation
      of pairs of propargyl-linked antifolates that possess similar physicochemical
      properties but different shapes. All of these compounds are effective at
      inhibiting the fungal enzymes and the growth of C. glabrata; however, the
      inhibition of the growth of C. albicans is shape-dependent with extended para
      linked compounds proving more effective than compact, meta-linked compounds.
      Using crystal structures of DHFR from C. albicans and C. glabrata bound to lead
      compounds, 13 new para-linked compounds designed to inhibit both species were
      synthesized. Eight of these compounds potently inhibit the growth of both fungal
      species with three compounds displaying dual MIC values less than 1 MUg/mL.
      Analysis of the active compounds shows that shape and distribution of polar
      functionality is critical in achieving dual antifungal activity. 

PMID- 24568659
TI  - Identification of the main toxins isolated from Fusarium oxysporum f. sp. pisi
      race 2 and their relation with isolates' pathogenicity.
AB  - Fusarium oxysporum f. sp. pisi (Fop) is a pathogen of field pea inducing severe
      vascular wilt worldwide. Plant resistance to races 1, 5, and 6, producing wilt
      symptoms, is conferred by a single dominant gene, while resistance to race 2,
      which gives near-wilt symptoms, have been recently showed to be quantitative.
      Among the virulence factors reported to play a role in the infection process,
      toxin production is one of the best studied. Thus, five race 2 isolates have been
      investigated for toxin production in vitro and their relation to isolates'
      pathogenicity. All the isolates produced different amounts of fusaric and 9,10
      dehydrofusaric acids. The content of the two toxins has been quantitated and
      correlated with the pathogenicity and aggressiveness of isolates on field pea.
      Results suggested that toxin production is an important determinant of Fop race 2
      pathogenicity. 

PMID- 24568660
TI  - Volatile disinfection byproducts resulting from chlorination of uric acid:
      implications for swimming pools.
AB  - Cyanogen chloride (CNCl) and trichloramine (NCl3) are important disinfection
      byproducts in chlorinated swimming pools. However, some unknowns exist regarding
      the precursors of their formation. In this study, uric acid is shown to be an
      efficient precursor to formation of CNCl and NCl3. The molar yields of CNCl and
      NCl3 were observed to be as high as 44% (pH = 6.0, chlorine/precursor molar ratio
      [Cl/P] = 6.4) and 108% (pH = 7.0, Cl/P = 30), respectively, both being strong
      functions of Cl/P, pH, and temperature. Analysis of swimming pool water samples,
      combined with the results of experiments involving chlorination of uric acid, and
      chlorination of body fluid analog mixtures, indicated that uric acid chlorination
      may account for a large fraction of CNCl formation in swimming pools. Moreover,
      given that uric acid introduction to pools is attributable to urination, a
      voluntary action for most swimmers, these findings indicate important benefits to
      pool water and air chemistry that could result from improved hygiene habits on
      the part of swimmers. 

PMID- 24568662
TI  - Dacryolith-induced acute dacryocystitis: a reversible cause of nasolacrimal duct
      obstruction.
AB  - AIMS: To report an unusual case of acute dacryocystits with fully patent
      nasolacrimal duct at follow-up after incision and curettage. CASE REPORT: A 63
      year-old patient with acute dacryocystitis and nasolacrimal duct abscess. CT
      orbits confirmed dacryocystitis without any orbital collection. Incision and
      drainage of the abscess was performed. RESULTS: Postoperative syringing of
      nasolacrimal duct demonstrated a fully patent nasolacrimal duct, with long term
      relief of epiphora. CONCLUSION: In some patients, dacryocystorhinostomy is not
      required after incision and drainage of a nasolacrimal abscess; reversible causes
      such as dacryoliths should always be considered.

PMID- 24568661
TI  - The Brief Obsessive-Compulsive Scale (BOCS): a self-report scale for OCD and
      obsessive-compulsive related disorders.
AB  - BACKGROUND: The Brief Obsessive Compulsive Scale (BOCS), derived from the Yale
      Brown Obsessive-Compulsive Scale (Y-BOCS) and the children's version (CY-BOCS),
      is a short self-report tool used to aid in the assessment of obsessive-compulsive
      symptoms and diagnosis of obsessive-compulsive disorder (OCD). It is widely used
      throughout child, adolescent and adult psychiatry settings in Sweden but has not
      been validated up to date. AIM: The aim of the current study was to examine the
      psychometric properties of the BOCS amongst a psychiatric outpatient population.
      METHOD: The BOCS consists of a 15-item Symptom Checklist including three items
      (hoarding, dysmorphophobia and self-harm) related to the DSM-5 category
      "Obsessive-compulsive related disorders", accompanied by a single six-item
      Severity Scale for obsessions and compulsions combined. It encompasses the
      revisions made in the Y-BOCS-II severity scale by including obsessive-compulsive
      free intervals, extent of avoidance and excluding the resistance item. 402 adult
      psychiatric outpatients with OCD, attention-deficit/hyperactivity disorder,
      autism spectrum disorder and other psychiatric disorders completed the BOCS.
      RESULTS: Principal component factor analysis produced five subscales titled
      "Symmetry", "Forbidden thoughts", "Contamination", "Magical thoughts" and
      "Dysmorphic thoughts". The OCD group scored higher than the other diagnostic
      groups in all subscales (P < 0.001). Sensitivities, specificities and internal
      consistency for both the Symptom Checklist and the Severity Scale emerged high
      (Symptom Checklist: sensitivity = 85%, specificities = 62-70% Cronbach's alpha =
      0.81; Severity Scale: sensitivity = 72%, specificities = 75-84%, Cronbach's alpha
      = 0.94). CONCLUSIONS: The BOCS has the ability to discriminate OCD from other non
      OCD related psychiatric disorders. The current study provides strong support for
      the utility of the BOCS in the assessment of obsessive-compulsive symptoms in
      clinical psychiatry.

PMID- 24568663
TI  - Class switch recombination process in ataxia telangiectasia patients with
      elevated serum levels of IgM.
AB  - Ataxia telangiectasia (AT) is a rare primary immunodeficiency disorder with
      various clinical manifestations. Increased serum levels of IgM and recurrent
      infections, mainly sinopulmonary infections, can be the presenting feature in a
      number of AT patients and may be initially misdiagnosed as hyper-IgM (HIgM)
      syndrome. This study was designed to investigate class switch recombination (CSR)
      as a critical mechanism in B lymphocytes' maturation to produce different
      isotypes of antibody in response to antigen stimulation in AT cases with HIgM
      presentation. Quantitative IgE production after stimulation by IL-4 and CD40L was
      considered as an indicator for CSR function. We also compared their results with
      sex and age matched AT patients without HIgM presentation. We report four AT
      patients with recurrent infections during infancy and high serum levels of IgM.
      Laboratory evaluations revealed defective CSR while none of the three AT patients
      without HIgM presentation had a defect in the CSR process. The characterized
      defect in AT is a mutation in the ataxia telangiectasia mutated (ATM) gene. This
      gene may result in CSR defects due to impaired DNA break repair. A special
      association between AT and HIgM may indicate a new subgroup of AT patients
      according to their clinical phenotype and CSR condition. 

PMID- 24568665
TI  - Three-dimensional perfusion cultivation of human cardiac-derived progenitors
      facilitates their expansion while maintaining progenitor state.
AB  - The therapeutic application of autologous cardiac-derived progenitor cells (CPCs)
      requires a large cell quantity generated under defined conditions. Herein, we
      investigated the applicability of a three-dimensional (3D) perfusion cultivation
      system to facilitate the expansion of CPCs harvested from human heart biopsies
      and characterized by a relatively high percentage of c-kit(+) cells. The cells
      were seeded in macroporous alginate scaffolds and after cultivation for 7 days
      under static conditions, some of the constructs were transferred into a perfusion
      bioreactor, which was operated for an additional 14 days. A robust and highly
      reproducible human CPC (hCPC) expansion of more than seven-fold was achieved
      under the 3D perfusion culture conditions, while under static conditions, the
      expansion of CPCs was limited only to the first 7 days, after which it leveled
      off. On day 21 of perfusion cultivation, the expanded cells exhibited a higher
      expression level of the progenitor marker c-kit, suggesting that the c-kit
      positive CPCs are the main cell population undergoing proliferation. The profile
      of the spontaneous differentiation in the perfused construct was different from
      that in the static cultivated constructs; genes typical for cardiac and
      endothelial cell lineages were more widely expressed in the perfused constructs.
      By contrast, the differentiation to osteogenic (Von Kossa staining and alkaline
      phosphatase activity) and adipogenic (Oil Red staining) lineages was reduced in
      the perfused constructs compared with static cultivated constructs. Collectively,
      our results indicate that 3D perfusion cultivation mode is an appropriate system
      for robust expansion of human CPCs while maintaining their progenitor state and
      differentiation potential into the cardiovascular cell lineages. 

PMID- 24568664
TI  - Three dimensional microfluidic cell arrays for ex vivo drug screening with
      mimicked vascular flow.
AB  - Currently, there are no reliable ex vivo models that predict anticancer drug
      responses in human tumors accurately. A comprehensive method of mimicking a 3D
      microenvironment to study effects of anticancer drugs on specific cancer types is
      essential. Here, we report the development of a three-dimensional microfluidic
      cell array (3D MUFCA), which reconstructs a 3D tumor microenvironment with cancer
      cells and microvascular endothelial cells. To mimic the in vivo spatial
      relationship between microvessels and nonendothelial cells embedded in
      extracellular matrix, three polydimethylsiloxane (PDMS) layers were built into
      this array. The multilayer property of the device enabled the imitation of the
      drug delivery in a microtissue array with simulated blood circulation. This 3D
      MUFCA system may provide better predictions of drug responses and identification
      of a suitable treatment for a specific patient if biopsy samples are used. To the
      pharmaceutical industry, the scaling-up of our 3D MUFCA system may offer a novel
      high throughput screening tool. 

PMID- 24568668
TI  - Seed/catalyst-free vertical growth of high-density electrodeposited zinc oxide
      nanostructures on a single-layer graphene.
AB  - We report the seed/catalyst-free vertical growth of high-density electrodeposited
      ZnO nanostructures on a single-layer graphene. The absence of
      hexamethylenetetramine (HMTA) and heat has resulted in the formation of nanoflake
      like ZnO structure. The results show that HMTA and heat are needed to promote the
      formation of hexagonal ZnO nanostructures. The applied current density plays
      important role in inducing the growth of ZnO on graphene as well as in
      controlling the shape, size, and density of ZnO nanostructures. High density of
      vertically aligned ZnO nanorods comparable to other methods was obtained. The
      quality of the ZnO nanostructures also depended strongly on the applied current
      density. The growth mechanism was proposed. According to the growth timing chart,
      the growth seems to involve two stages which are the formation of ZnO nucleation
      and the enhancement of the vertical growth of nanorods. ZnO/graphene hybrid
      structure provides several potential applications in electronics and
      optoelectronics such as photovoltaic devices, sensing devices, optical devices,
      and photodetectors. 

PMID- 24568667
TI  - Binding between DNA and carbon nanotubes strongly depends upon sequence and
      chirality.
AB  - Certain single-stranded DNA (ssDNA) sequences are known to recognize their
      partner single-walled carbon nanotube (CNT). Here, we report on activation
      energies for the removal of several ssDNA sequences from a few CNT species by a
      surfactant molecule. We find that DNA sequences systematically have higher
      activation energy on their CNT recognition partner than on non-partner species.
      For example, the DNA sequence (TAT)4 has much lower activation energy on the
      (9,1) CNT than on its partner (6,5) CNT, whereas the DNA sequence (CCA)10 binds
      strongly to its partner (9,1) CNT compared to (6,5) CNT. The (6,5) and (9,1) CNTs
      have the same diameter but different electronic properties, suggesting that the
      activation energy difference is related to electronic properties. The activation
      energies of increasing lengths of closely related sequences from the 11-mer
      (TAT)3TA to the 21-mer (TAT)7 on three different CNT species (9,1), (6,5), and
      (8,3) were measured. For the shorter sequences, the activation energy on the CNT
      varies periodically with the sequence. 

PMID- 24568666
TI  - Exogenous interleukin-10 alleviates allergic inflammation but inhibits local
      interleukin-10 expression in a mouse allergic rhinitis model.
AB  - BACKGROUND: Interleukin-10 (IL-10) has an important anti-inflammatory and
      immunoregulatory function, and its expression is negatively correlated with the
      development and severity of allergic rhinitis (AR). However, the in vivo effects
      of exogenous IL-10 on AR have not been studied and the mechanisms underlying the
      effects of IL-10 have not been fully understood. Here, we investigated the
      effects of intranasal administration of recombinant mouse (rm) IL-10 on the
      expression of Th responses and local IL-10 in a mouse model of AR induced by
      ovalbumin. RESULTS: Administration of rmIL-10 during challenge significantly
      reduced the number of eosinophils and mast cells, as well as Type 2 helper T
      (Th2) and Th17 cell related cytokine and transcription factor levels in the nasal
      mucosa and nasal lavage fluid in AR mice. The rmIL-10 treatment significantly
      inhibited the number of IL-10-positive cells and IL-10 mRNA expression in the
      nasal mucosa in AR mice. CONCLUSION: Our results show that exogenous IL-10
      administrated in challenge phase alleviates nasal allergic inflammation in AR
      mice, most likely by inhibiting Th2 and Th17 responses. It can also inhibit local
      IL-10 levels in the nasal mucosa. Our findings indicate that IL-10 may have the
      potential as an inhibitor of AR.

PMID- 24568670
TI  - Metallothionein as a therapeutic molecular target against human diseases.

PMID- 24568669
TI  - Xanthine oxidase and cardiovascular risk in obese children.
AB  - BACKGROUND: Pathological mechanisms of how childhood obesity leads to increased
      risk of cardiovascular disease (CVD) are not fully characterized. Oxidative
      stress-related enzymes, such as xanthine oxidase (XO), have been linked to
      obesity, endothelial dysfunction, and CVD in adults, but little is known about
      this pathway in children. The aim of this study was to determine whether
      differential XO activity is associated with endothelial dysfunction, CVD risk
      factors, or cytokine levels. METHODS: Fasting plasma samples were obtained from
      obese (BMI >= 95th percentile; n = 20) and age- and gender-matched healthy weight
      (BMI > 5th and < 85th percentile; n = 22) children and adolescents (mean age, 12
      +/- 3 years) to quantify XO activity. In addition, fasting cholesterol, insulin,
      glucose, blood pressure, endothelial function, and cytokine levels were assessed.
      RESULTS: We observed a 3.8-fold increase in plasma XO activity in obese, compared
      to healthy weight, children (118 +/- 21 vs. 31 +/- 9  nU/mg of protein; p <
      0.001). Plasma XO activity was correlated with BMI z-score (r = 0.41), waist
      circumference (r = 0.41), high-density lipoprotein cholesterol (r = -0.32),
      oxidized low-density lipoprotein (r = 0.57), adiponectin (r = -0.53), and
      monocyte chemotactic protein-1 (r = -0.59). CONCLUSION: XO activity is highly
      elevated in obese children and correlates with CVD risk factors, suggesting that
      XO may play a role in increasing cardiovascular risk early in life in the context
      of obesity.

PMID- 24568672
TI  - Examining targets for HIV prevention: intravaginal practices in Urban Lusaka,
      Zambia.
AB  - Intravaginal practices (IVP) are the introduction of products inside the vagina
      for hygienic, health, or sexuality reasons. The influence of men and Alengizis,
      traditional marriage counselors for girls, in promoting IVP has not been
      explored. We conducted gender-concordant focus groups and key informant
      interviews with Alengizis. The responses were conducted grouped into three
      themes: (1) cultural norms, (2) types and reasons for IVP, and (3) health
      consequences. We found that IVP were used by all participants in our sample and
      were taught from generation to generation by friends, relatives, or Alengizis.
      The reasons for women to engage in IVP were hygienic, though men expect women to
      engage in IVP to enhance sexual pleasure. Approximately 40% of women are aware
      that IVP can facilitate genital infections, but felt they would not feel clean
      discontinuing IVP. All men were unaware of the vaginal damage caused by IVP, and
      were concerned about the loss of sexual pleasure if women discontinued IVP.
      Despite the health risks of IVP, IVP continue to be widespread in Zambia and an
      integral component of hygiene and sexuality. The frequency of IVP mandates
      exploration into methods to decrease or ameliorate their use as an essential
      component of HIV prevention.

PMID- 24568671
TI  - Triglycerides as a biological marker of repeated re-hospitalization resulting
      from deliberate self-harm in acute psychiatry patients: a prospective
      observational study.
AB  - BACKGROUND: Biological factors have been associated with deliberate self-harm
      (DSH) but have not been integrated with clinical factors in routine risk
      assessments.This study aimed to examine the incremental validity of lipid levels
      and platelet serotonin when combined with psychosocial factors in risk
      assessments for repeated admissions due to DSH. METHODS: In this prospective
      observational study of 196 acutely admitted patients, results of blood tests
      performed upon admission and the MINI Suicidal Scale and psychosocial DSH risk
      factor assessments performed at discharge were compared with the incidence of DSH
      recorded during the first 3 and 12 months after discharge. RESULTS: High
      triglyceride levels were found to be a significant marker for patients admitted 3
      or more times due to DSH (repeated DSH, DSH-R) when tested against other
      significant risk factors. When all (9) significant univariate factors associated
      with 12-month post-discharge DSH-R were analyzed in a multivariate logistic
      regression, the MINI Suicidal Scale (p = 0.043), a lack of insight (p = 0.040),
      and triglyceride level (p = 0.020) remained significant. The estimated 12-month
      area under the curve of the receiver operator characteristic (ROC-AUC) for DSH-R
      was 0.74 for triglycerides, 0.81 for the MINI, 0.89 for the MINI + psychosocial
      factors, and 0.91 for the MINI + psychosocial factors + triglycerides. The
      applied multifaceted approach also significantly discriminated between 12-month
      post-discharge DSH-R patients and other DSH patients, and a lack of insight (p =
      0.047) and triglycerides (p = 0.046) remained significant for DSH-R patients in a
      multivariate analysis in which other DSH patients served as the reference group
      (rather than non-DSH patients). CONCLUSION: The triglyceride values provided
      incremental validity to the MINI Suicidal Scale and psychosocial risk factors in
      the assessment of the risk of repeated DSH. Therefore, a bio-psychosocial
      approach appears promising, but further research is necessary to refine and
      validate this method.

PMID- 24568674
TI  - N-aryl-2,6-dimethylbenzamides, a new generation of tocainide analogues as
      blockers of skeletal muscle voltage-gated sodium channels.
AB  - On the basis of a 3D-QSAR study, a new generation of tocainide analogues were
      designed and synthesized as voltage-gated skeletal muscle sodium channel
      blockers. Data obtained by screening new compounds by means of Hille-Campbell
      Vaseline gap voltage-clamp recordings showed that the elongation of the alkyl
      chain and the introduction of lipophilic and sterically hindered groups on the
      amino function enhance both potency and use-dependent block. The results provide
      additional indications about the structural requirement of pharmacophores for
      further increasing potency and state-dependent block and allowed us to identify a
      new tocainide analogue (6f) with a favorable pharmacodynamic profile to be
      proposed as a valid candidate for studies aimed at evaluating its usefulness in
      the treatment of myotonias. 

PMID- 24568675
TI  - Risk factors for abdominal bleeding after living-donor liver transplant.
AB  - OBJECTIVES: The purpose of this study was to identify the incidence, outcomes,
      and risk factors of postoperative abdominal bleeding after living-donor liver
      transplant. MATERIALS AND METHODS: Adult patients who had living-donor liver
      transplant between 2001 and 2013 were evaluated. Preoperative and intraoperative
      variables of transplant recipients were analyzed retrospectively with univariate
      analysis. Cox proportional hazards regression model was used to identify
      independent factors for postoperative bleeding. RESULTS: There were 241 living
      donor liver transplant recipients included in the study. Postoperative abdominal
      bleeding was observed in 12 recipients (5%). The 3-month cumulative survival was
      significantly lower in recipients who had postoperative bleeding (survival, 8
      patients [67%]) than recipients who did not have postoperative bleeding
      (survival, 204 patients [89%]; P = .009). Univariate analysis showed that
      preoperative albumin level, Child-Pugh class, and intraoperative blood loss were
      risk factors for postoperative bleeding. In multivariate analysis, intraoperative
      blood loss and Child-Pugh status were significant risk factors for postoperative
      bleeding. CONCLUSIONS: Living-donor liver transplant recipients who had
      postoperative bleeding had a poor outcome. Postoperative bleeding was associated
      with higher intraoperative blood loss and Child-Pugh class.

PMID- 24568673
TI  - The practice of venous blood collection among laboratory and non-laboratory
      professionals working in Ethiopian Government Hospitals: a comparative study.
AB  - BACKGROUND: Pre-analytical phase of overall laboratory testing system continues
      to be the major source of errors that affect patient safety and health care
      system. One of the activities in this phase is venous blood collection (VBC), the
      most common type of specimen drawn or sent to clinical laboratories for further
      analysis; and the source for a potentially numerous types of errors. In this
      study, we focused on determining and comparing desirability/undesirability of
      activities during VBC in Ethiopian hospitals among different groups of
      professionals. METHODS: We conducted a cross-sectional comparative study in three
      government hospitals in South Ethiopia from February 2012 to September 2012.
      Randomly selected professionals who participate in VBC in outpatient and
      inpatient departments were requested to fill in structured and pretested
      questionnaire regarding their practice of VBC and their replies were categorized
      as 'desirable' and 'undesirable' according to Clinical and Laboratory Standards
      Institute (CLSI) standard. Then, data was analyzed using Medcalc(r) version
      12.1.4 software. P value of less than 0.05 was considered as statistically
      significant. RESULTS: In our study, 120 professionals were included among which
      15.8% (n = 19) were laboratory professionals while the remaining 84.2% (n = 101)
      were non-laboratory professionals. Conscious patient identification in pre
      collection phase of VBC and position of patients' hands in actual collection
      phase of VBC involved the highest proportion of undesirability among both groups
      of professionals. However, in the post collection phase, specimen transferring
      from syringes to test tubes (15.8%) and mixing specimen with additives (63.4%)
      involved highest proportions of undesirability among laboratory and non
      laboratory professionals respectively. Laboratory professionals reported better
      desirable practice in patient identification frequency, labeling and checking
      expiry dates of test tubes, specimen transfer and transport practices.
      CONCLUSION: In conclusion, preparatory activities of VBC involved the highest
      proportions of undesirable practices among both groups of professionals. However,
      relatively better proportions of desirability were seen among laboratory
      professionals than non-laboratory professionals in some pre- and post-collection
      phase activities. The difference might be seen as a result of better
      qualification, education and training experience on VBC among laboratory
      professionals.

PMID- 24568676
TI  - Catalytic decomposition of toxic chemicals over iron group metals supported on
      carbon nanotubes.
AB  - This study explores catalytic decomposition of phosphine (PH3) using iron group
      metals (Co, Ni) and metal oxides (Fe2O3, Co(3)O4, NiO) supported on carbon
      nanotubes (CNTs). The catalysts are synthesized by means of a deposition
      precipitation method. The morphology, structure, and composition of the catalysts
      are characterized using a number of analytical instrumentations, including high
      resolution transmission electron microscopy, X-ray diffraction, X-ray
      photoelectron spectroscopy, BET surface area measurement, and inductively coupled
      plasma. The activity of the catalysts in the PH3 decomposition reaction is
      measured and correlated with their surface and structural properties. The
      characterization results show that phosphidation occurs on the catalyst surface,
      and the resulting metal phosphides act as an active phase in the PH3
      decomposition reaction. Cobalt phosphide, CoP, is formed on Co/CNTs and
      Co(3)O4/CNTs, whereas iron phosphide, FeP, is formed on Fe2O3/CNTs. In contrast,
      phosphorus-rich phosphide NiP2 is formed on Ni/CNTs and NiO/CNTs. The initial
      activities of the catalysts are shown in the following sequence: Ni/CNTs >
      Co/CNTs > Co(3)O4/CNTs >NiO/CNTs > Fe2O3/CNTs, whereas activities of metal
      phosphides are shown in the following order: CoP > NiP2 > FeP. The catalytic
      activity of metal phosphides is attributed to their electronic properties. Cobalt
      phosphide formed on Co/CNTs and Co(3)O4/CNTs exhibits not only the highest
      activity, but also long-term stability in the PH3 decomposition reaction.

PMID- 24568677
TI  - Transcaruncular medial canthal tendon plication with lower eyelid suture sling in
      facial nerve palsy.
AB  - PURPOSE: To report a technique for correcting lower eyelid punctal ectropion with
      an inferiorly displaced or retracted medial eyelid due to facial nerve palsy, by
      extending a suture sling along the pre-tarsal lower eyelid when performing
      transcaruncular medial canthal tendon plication. METHODS: Single-centre
      retrospective, non-comparative review of patients with facial nerve palsy who
      underwent medial canthal tendon plication with lower eyelid suture sling (MCT
      suture sling). Outcome measures included: the presence of lower eyelid ectropion,
      medial eyelid height, punctal position, inferior marginal reflex distance (MRD)
      and inferior scleral show measured both pre-operatively and at the last follow-up
      visit. RESULTS: Thirty-three patients with facial nerve palsy with a mean age of
      59, underwent MCT suture sling for lagophthalmos and/or ectropion. Then, 66%
      (21/32) of cases had punctal ectropion pre-operatively and 9% (3/32) had punctal
      ectropion at the last follow-up. Medial eyelid height was deemed to improve in
      66% (21/32) of cases at the last follow up visit. Follow-up was mean 13.5 months.
      Six (18%) patients were deemed failures due to inferior MRD and inferior scleral
      showing worse than pre-operative measurements. DISCUSSION: We report a technique
      for incorporating a suture sling to transcaruncular-approach MCT plication when
      the medial canthus has retracted or descended thus requiring support and a
      posterior vector. It avoids rounding of the medial canthal angle that may occur
      with traditional medial canthoplasty. Transcaruncular MCT plication is well
      described. Incorporating a suture sling to potentially reduce single point
      fixation cheese-wiring and early dehiscence is minimally invasive, non-excisional
      and repeatable.

PMID- 24568678
TI  - Insights into the coassembly of hydrogelators and surfactants based on aromatic
      peptide amphiphiles.
AB  - The coassembly of small molecules is a useful means of increasing the complexity
      and functionality of their resultant supramolecular constructs in a modular
      fashion. In this study, we explore the assembly and coassembly of serine
      surfactants and tyrosine-leucine hydrogelators, capped at the N-termini with
      either fluorenyl-9-methoxycarbonyl (Fmoc) or pyrene. These systems all exhibit
      self-assembly behavior, which is influenced by aromatic stacking interactions,
      while the hydrogelators also exhibit beta-sheet-type arrangements, which
      reinforce their supramolecular structures. We provide evidence for three distinct
      supramolecular coassembly models; cooperative, disruptive, and orthogonal. The
      coassembly mode adopted depends on whether the individual constituents (I) are
      sufficiently different, such that effective segregation and orthogonal assembly
      occurs; (II) adhere to a communal mode of self-assembly; or (III) act to
      compromise the assembly of one another via incorporation and disruption. We find
      that a greater scope for controllable coassembly exists within orthogonal
      systems; which show minimal relative changes in the native gelator's
      supramolecular structure by Fourier transform infrared spectroscopy (FTIR),
      circular dichroism (CD), and fluorescence spectroscopy. This is indicative of the
      segregation of orthogonal coassembly constituents into distinct domains, where
      surfactant chemical functionality is presented at the surface of the gelator's
      supramolecular fibers. Overall, this work provides new insights into the design
      of modular coassembly systems, which have the potential to augment the chemical
      and physical properties of existing gelator systems. 

PMID- 24568680
TI  - Three-terminal nanoelectromechanical field effect transistor with abrupt
      subthreshold slope.
AB  - We report the first experimental demonstration of a three-terminal
      nanoelectromechanical field effect transistor (NEMFET) with measurable
      subthreshold slope as small as 6 mV/dec at room temperature and a switching
      voltage window of under 2 V. The device operates by modulating drain current
      through a suspended nanowire channel via an insulated gate electrode, thus
      eliminating the need for a conducting moving electrode, and yields devices that
      reliably switch on/off for up to 130 cycles. Radio-frequency measurements have
      confirmed operation at 125 MHz. Our measurements and simulations suggest that the
      NEMFET design is scalable toward sub-1 V ultrahigh-frequency operation for future
      low-power computing systems. 

PMID- 24568679
TI  - Coexpression of beta-D-galactosidase and L-arabinose isomerase in the production
      of D-tagatose: a functional sweetener.
AB  - The functional sweetener, d-tagatose, is commonly transformed from galactose by l
      arabinose isomerase. To make use of a much cheaper starting material, lactose,
      hydrolization, and isomerization are required to take place collaboratively.
      Therefore, a single-step method involving beta-d-galactosidase was explored for d
      tagatose production. The two vital genes, beta-d-galactosidase gene (lacZ) and l
      arabinose isomerase mutant gene (araA') were extracted separately from
      Escherichia coli strains and incorporated into E. coli simultaneously. This gave
      us E. coli-ZY, a recombinant producing strain capable of coexpressing the two key
      enzymes. The resulted cells exhibited maximum d-tagatose producing activity at 34
      degrees C and pH 6.5 and in the presence of borate, 10 mM Fe(2+), and 1 mM
      Mn(2+). Further monitoring showed that the recombinant cells could hydrolyze more
      than 95% lactose and convert 43% d-galactose into d-tagatose. This research has
      verified the feasibility of single-step d-tagatose fermentation, thereby laying
      down the foundation for industrial usage of lactose.

PMID- 24568681
TI  - Reactivity of ruthenium phosphido species generated through the deprotonation of
      a tripodal phosphine ligand and implications for hydrophosphination.

PMID- 24568682
TI  - In vivo high-content evaluation of three-dimensional scaffolds biocompatibility.
AB  - While developing tissue engineering strategies, inflammatory response caused by
      biomaterials is an unavoidable aspect to be taken into consideration, as it may
      be an early limiting step of tissue regeneration approaches. We demonstrate the
      application of flat and flexible films exhibiting patterned high-contrast
      wettability regions as implantable platforms for the high-content in vivo study
      of inflammatory response caused by biomaterials. Screening biomaterials by using
      high-throughput platforms is a powerful method to detect hit spots with promising
      properties and to exclude uninteresting conditions for targeted applications.
      High-content analysis of biomaterials has been mostly restricted to in vitro
      tests where crucial information is lost, as in vivo environment is highly
      complex. Conventional biomaterials implantation requires the use of high numbers
      of animals, leading to ethical questions and costly experimentation. Inflammatory
      response of biomaterials has also been highly neglected in high-throughput
      studies. We designed an array of 36 combinations of biomaterials based on an
      initial library of four polysaccharides. Biomaterials were dispensed onto
      biomimetic superhydrophobic platforms with wettable regions and processed as
      freeze-dried three-dimensional scaffolds with a high control of the array
      configuration. These chips were afterward implanted subcutaneously in Wistar
      rats. Lymphocyte recruitment and activated macrophages were studied on-chip, by
      performing immunocytochemistry in the miniaturized biomaterials after 24 h and 7
      days of implantation. Histological cuts of the surrounding tissue of the implants
      were also analyzed. Localized and independent inflammatory responses were
      detected. The integration of these data with control data proved that these chips
      are robust platforms for the rapid screening of early-stage in vivo biomaterials'
      response.

PMID- 24568683
TI  - Mycobacterium bovis ornithine carbamoyltransferase, MB1684, induces
      proinflammatory cytokine gene expression by activating NF-kappaB in macrophages.
AB  - Mycobacterium bovis is the etiological factor of bovine tuberculosis (BTB),
      posing a significant problem to domestic cattle. The bacterium is also zoonotic,
      affecting human health worldwide. Macrophage evasion of the bacterium involves
      mycobacterial molecules such as MB1684 (ornithine carbamoyltransferase). In this
      study, we confirmed a concentration-dependent decrease in proliferation of Ana-1
      macrophages when treated with rMB1684 when compared with mycobacterium bovis
      purified protein derivative of tuberculosis (MbPPD) or phosphate buffer solution
      incubation groups. We examined the activation of nuclear factor-kappa B (NF
      kappaB) upon exposure to MB1684, and its role in MB1684-induced upregulation of
      interferon (IFN)-gamma and proinflammatory cytokines (interleukin [IL]-1beta, IL
      6, and tumor necrosis factor-alpha) in Ana-1 macrophages. The levels of
      proinflammatory cytokines and IFN-gamma were significantly high in MB1684-treated
      Ana-1 macrophages. The treatment led to an increase in NF-kappaB activation and a
      high expression of the just mentioned proinflammatory cytokines. NF-kappaB
      inhibition significantly abrogated MB1684-induced upregulation of proinflammatory
      cytokine mRNA expression, which suggests that MB1684-induced activation of NF
      kappaB in turn stimulates gene expression of IFN-gamma and proinflammatory
      cytokines in Ana-1 macrophages. The experiment was repeated in bone marrow
      macrophages, a more in-vivo-like model system, and similar results validated our
      conclusion. Further, we identified the possibility of the application of MB1684
      antigen for the detection of BTB in cattle serum. 

PMID- 24568684
TI  - Healthcare seeking and hospital admissions by people who inject drugs in response
      to symptoms of injection site infections or injuries in three urban areas of
      England.
AB  - People who inject drugs (PWID) are vulnerable to infections and injuries at
      injection sites. The factors associated with reporting symptoms of these, seeking
      related advice, and hospital admission are examined. PWID were recruited in
      Birmingham, Bristol and Leeds using respondent-driven sampling (N = 855). During
      the preceding year, 48% reported having redness, swelling and tenderness (RST),
      19% an abscess, and 10% an open wound at an injection site. Overall, 54% reported
      ?1 symptoms, with 45% of these seeking medical advice (main sources emergency
      departments and General Practitioners). Advice was often sought ?5 days after the
      symptom first appeared (44% of those seeking advice about an abscess, 45% about
      an open wound, and 35% for RST); the majority received antibiotics. Overall, 9.5%
      reported hospital admission during the preceding year. Ever being diagnosed with
      septicaemia and endocarditis were reported by 8.8% and 2.9%, respectively.
      Interventions are needed to reduce morbidity, healthcare burden and delays in
      accessing treatment.

PMID- 24568685
TI  - The effectiveness of an anti-stigma intervention in a basic police officer
      training programme: a controlled study.
AB  - BACKGROUND: Stigma and discrimination are still prominent features of the life
      situation of persons with mental illness, adding to the burden of the illness,
      causing a lowered self-esteem, quality of life and affecting possibilities of
      adequate housing and work. It is also a major barrier to help seeking. The
      deinstitutionalization of mental health services has led to a significant
      increase in contacts between the police and persons with mental illness. It has
      been argued that police officers should be provided education and training to
      enable them to interact adaptively and with good outcomes with people with mental
      illness. The present study is investigating the effectiveness of an anti-stigma
      intervention in a basic police officer training programme at a university in
      Sweden. METHODS: The study was performed as a controlled pre-post intervention
      study using a comparison group, and a 6-month follow-up of the intervention
      group. Attitudes, mental health literacy and intentional behaviour were assessed.
      Main analyses were made on an intention to treat basis using repeated measures
      ANOVA. A total of 120 participants at a basic police officer training programme
      were included. RESULTS: Time by group analyses showed improvements in the
      intervention group in overall score of attitudes and regarding the subscale Open
      minded and pro integration, in intentional behaviour (willingness to work with)
      and in 4 out of 6 items assessing mental health literacy. At the 6-month follow
      up the intervention group had, as compared to baseline, improved attitudes in
      both overall score and in two of the subscales. Intentional behaviour had also
      improved in terms of an increased willingness to live or work with a person with
      mental health problems. Mental health literacy had improved in 3 out of 6 items.
      CONCLUSIONS: The anti-stigma intervention proved to be effective in changing
      attitudes, mental health literacy and intentional behaviour. Improvements mainly
      endured at the 6-month follow-up. The intervention seems promising in
      facilitating encounters between the police and persons with mental illness.
      Further studies are needed to disentangle the relative effectiveness of the
      components of the intervention before further implementation.

PMID- 24568686
TI  - Dissecting the insect metabolic machinery using twin ion mass spectrometry: a
      single P450 enzyme metabolizing the insecticide imidacloprid in vivo.
AB  - Insecticide resistance is one of the most prevalent examples of anthropogenic
      genetic change, yet our understanding of metabolic-based resistance remains
      limited by the analytical challenges associated with rapidly tracking the in vivo
      metabolites of insecticides at nonlethal doses. Here, using twin ion mass
      spectrometry analysis of the extracts of whole Drosophila larvae and excreta, we
      show that (i) eight metabolites of the neonicotinoid insecticide, imidacloprid,
      can be detected when formed by susceptible larval genotypes and (ii) the specific
      overtranscription of a single gene product, Cyp6g1, associated with the metabolic
      resistance to neonicotinoids, results in a significant increase in the formation
      of three imidacloprid metabolites that are formed in C-H bond activation
      reactions; that is, Cyp6g1 is directly linked to the enhanced metabolism of
      imidacloprid in vivo. These results establish a rapid and sensitive method for
      dissecting the metabolic machinery of insects by directly linking single gene
      products to insecticide metabolism. 

PMID- 24568687
TI  - Cytomegalovirus glomerulopathy and cytomegalovirus interstitial nephritis on
      sequential transplant kidney biopsies.
AB  - Cytomegalovirus (CMV) nephropathy may be seen in kidney transplant biopsy
      specimens. We report a CMV-negative patient who received a kidney transplant from
      a CMV-positive donor and subsequently developed CMV glomerulopathy and CMV
      associated interstitial nephritis, as observed in 2 sequential kidney biopsies.
      The first biopsy specimen showed CMV-positive endothelial cells in glomerular
      capillaries and CMV-infected monocytes in glomerular capillary lumens. The second
      biopsy specimen showed CMV-positive cells in the interstitium with associated
      lymphoplasmacytic infiltrate and tubular injury, but no evidence of direct CMV
      infection in tubular epithelial cells. Moreover, the second biopsy specimen
      showed persistent monocytes with cytoplasmic viral particles within glomerular
      capillary loops by electron microscopy. Our case shows that CMV glomerulopathy
      can be caused by direct CMV infection of glomerular capillary endothelial cells.
      CMV-positive circulating monocytes may play an important role in the different
      histopathologic manifestations of CMV nephropathy in kidney transplant grafts.

PMID- 24568688
TI  - High-throughput screening and whole genome sequencing identifies an
      antimicrobially active inhibitor of Vibrio cholerae.
AB  - BACKGROUND: Pathogenic serotypes of Vibrio cholerae cause the life-threatening
      diarrheal disease cholera. The increasing development of bacterial resistances
      against the known antibiotics necessitates the search for new antimicrobial
      compounds and targets for this pathogen. RESULTS: A high-throughput screening
      assay with a Vibrio cholerae reporter strain constitutively expressing green
      fluorescent protein (GFP) was developed and applied in the investigation of the
      growth inhibitory effect of approximately 28,300 structurally diverse natural
      compounds and synthetic small molecules. Several compounds with activities in the
      low micromolar concentration range were identified. The most active structure,
      designated vz0825, displayed a minimal inhibitory concentration (MIC) of 1.6 MUM
      and a minimal bactericidal concentration (MBC) of 3.2 MUM against several strains
      of V. cholerae and was specific for this pathogen. Mutants with reduced
      sensitivity against vz0825 were generated and whole genome sequencing of 15
      pooled mutants was carried out. Comparison with the genome of the wild type
      strain identified the gene VC_A0531 (GenBank: AE003853.1) as the major site of
      single nucleotide polymorphisms in the resistant mutants. VC_A0531 is located on
      the small chromosome of V. cholerae and encodes the osmosensitive K+-channel
      sensor histidine kinase (KdpD). Nucleotide exchange of the major mutation site in
      the wild type strain confirmed the sensitive phenotype. CONCLUSION: The reporter
      strain MO10 pG13 was successfully used for the identification of new
      antibacterial compounds against V. cholerae. Generation of resistant mutants and
      whole genome sequencing was carried out to identify the histidine kinase KdpD as
      a novel antimicrobial target.

PMID- 24568689
TI  - Toward in silico biomolecular manipulation through static modes: atomic scale
      characterization of HIV-1 protease flexibility.
AB  - Probing biomolecular flexibility with atomic-scale resolution is a challenging
      task in current computational biology for fundamental understanding and
      prediction of biomolecular interactions and associated functions. This paper
      makes use of the static mode method to study HIV-1 protease considered as a model
      system to investigate the full biomolecular flexibility at the atomic scale, the
      screening of active site biomechanical properties, the blind prediction of
      allosteric sites, and the design of multisite strategies to target deformations
      of interest. Relying on this single calculation run of static modes, we
      demonstrate that in silico predictive design of an infinite set of complex
      excitation fields is reachable, thanks to the storage of the static modes in a
      data bank that can be used to mimic single or multiatom contact and efficiently
      anticipate conformational changes arising from external stimuli. All along this
      article, we compare our results to data previously published and propose a
      guideline for efficient, predictive, and custom in silico experiments. 

PMID- 24568691
TI  - Contactless and non-invasive delivery of micro-particles lying on a non
      customized rigid surface by using acoustic radiation force.
AB  - In the existing acoustic micro-particle delivery methods, the micro-particles
      always lie and slide on the surface of platform in the whole delivery process. To
      avoid the damage and contamination of micro-particles caused by the sliding
      motion, this paper deals with a novel approach to trap micro-particles from non
      customized rigid surfaces and freely manipulate them. The delivery process
      contains three procedures: detaching, transporting, and landing. Hence, the micro
      particles no longer lie on the surface, but are levitated in the fluid, during
      the long range transporting procedure. It is very meaningful especially for the
      fragile and easily contaminated targets. To quantitatively analyze the delivery
      process, a theoretical model to calculate the acoustic radiation force exerting
      upon a micro-particle near the boundary in half space is built. An experimental
      device is also developed to validate the delivery method. A 100 MUm diameter
      micro-silica bead adopted as the delivery target is detached from the upper
      surface of an aluminum platform and levitated in the fluid. Then, it is
      transported along the designated path with high precision in horizontal plane.
      The maximum deviation is only about 3.3 MUm. During the horizontal
      transportation, the levitation of the micro-silica bead is stable, the maximum
      fluctuation is less than 1 MUm. The proposed method may extend the application of
      acoustic radiation force and provide a promising tool for microstructure or cell
      manipulation.

PMID- 24568690
TI  - Patient engagement in research: a systematic review.
AB  - BACKGROUND: A compelling ethical rationale supports patient engagement in
      healthcare research. It is also assumed that patient engagement will lead to
      research findings that are more pertinent to patients' concerns and dilemmas.
      However; it is unclear how to best conduct this process. In this systematic
      review we aimed to answer 4 key questions: what are the best ways to identify
      patient representatives? How to engage them in designing and conducting research?
      What are the observed benefits of patient engagement? What are the harms and
      barriers of patient engagement? METHODS: We searched MEDLINE, EMBASE, PsycInfo,
      Cochrane, EBSCO, CINAHL, SCOPUS, Web of Science, Business Search Premier,
      Academic Search Premier and Google Scholar. Included studies were published in
      English, of any size or design that described engaging patients or their
      surrogates in research design. We conducted an environmental scan of the grey
      literature and consulted with experts and patients. Data were analyzed using a
      non-quantitative, meta-narrative approach. RESULTS: We included 142 studies that
      described a spectrum of engagement. In general, engagement was feasible in most
      settings and most commonly done in the beginning of research (agenda setting and
      protocol development) and less commonly during the execution and translation of
      research. We found no comparative analytic studies to recommend a particular
      method. Patient engagement increased study enrollment rates and aided researchers
      in securing funding, designing study protocols and choosing relevant outcomes.
      The most commonly cited challenges were related to logistics (extra time and
      funding needed for engagement) and to an overarching worry of a tokenistic
      engagement. CONCLUSIONS: Patient engagement in healthcare research is likely
      feasible in many settings. However, this engagement comes at a cost and can
      become tokenistic. Research dedicated to identifying the best methods to achieve
      engagement is lacking and clearly needed.

PMID- 24568692
TI  - Fecal calprotectin in healthy children.
AB  - Calprotectin is a protein found in the cytosol of inflammatory cells and is a
      marker of the presence and the degree of inflammation in the bowel system.
      Calprotectin in feces has great diagnostic value in the matter of inflammatory
      bowel disease (IBD). In feces, the protein is stable up to seven days, and since
      the protein can easily be measured with an ELISA, the use of fecal calprotectin
      (FC) means no invasive measures. For adults and children over 4 years, a cut-off
      level of 50 mg/kg has been well established for diagnostic purposes. Because
      previous studies have proven that children under the age of four in general have
      higher FC values than older children and adults, there is a need for a cut-off
      level for this age group. In order to establish that, the normal values for FC in
      children from 0-4 years were investigated. Some 75 stool samples from healthy
      children were collected and the levels of FC were analyzed. The results were
      compared to 157 pediatric cases where FC analysis had been performed for
      diagnostic purposes. As a result, three cut-off levels were established based on
      the 97.5% percentiles of FC in different age groups: 538 mg/kg (1 < 6 months),
      214 mg/kg (6 months < 3 years) and 75 mg/kg (3 < 4 years).

PMID- 24568693
TI  - Immobilization of mercury by carboxymethyl cellulose stabilized iron sulfide
      nanoparticles: reaction mechanisms and effects of stabilizer and water chemistry.
AB  - Iron sulfide (FeS) nanoparticles were prepared with sodium carboxymethyl
      cellulose (CMC) as a stabilizer, and tested for enhanced removal of aqueous
      mercury (Hg(2+)). CMC at >=0.03 wt % fully stabilized 0.5 g/L of FeS (i.e., CMC
      to-FeS molar ratio >=0.0006). FTIR spectra suggested that CMC molecules were
      attached to the nanoparticles through bidentate bridging and hydrogen bonding.
      Increasing the CMC-to-FeS molar ratio from 0 to 0.0006 enhanced mercury sorption
      capacity by 20%; yet, increasing the ratio from 0.0010 to 0.0025 diminished the
      sorption by 14%. FTIR and XRD analyses suggested that precipitation (formation of
      cinnabar and metacinnabar), ion exchange (formation of Hg0.89Fe0.11S), and
      surface complexation were important mechanisms for mercury removal. A pseudo
      second-order kinetic model was able to interpret the sorption kinetics, whereas a
      dual-mode isotherm model was proposed to simulate the isotherms, which considers
      precipitation and adsorption. High mercury uptake was observed over the pH range
      of 6.5-10.5, whereas significant capacity loss was observed at pH < 6. High
      concentrations of Cl(-) (>106 mg/L) and organic matter (5 mg/L as TOC) modestly
      inhibited mercury uptake. The immobilized mercury remained stable when preserved
      for 2.5 years at pH above neutral. 

PMID- 24568694
TI  - HIV-Related discrimination in European health care settings.
AB  - This cross-sectional European study assessed self-reported HIV-related
      discrimination and its associated factors in health care settings. Socio
      demographics, health status, support needs relating to sexual and reproductive
      health (SRH), and self-reported HIV-related discrimination were measured using an
      anonymous survey in a sample of 1549 people living with HIV from 14 countries.
      Thirty-two per cent of the participants had experienced HIV-related
      discrimination during the previous 3 years; almost half of them felt
      discriminated against by health care providers. For this type of discrimination,
      logistic regression analysis revealed significant associations with not being a
      migrant (OR: 2.0; IC 1.0-3.7; p<0.05), having been forced into sexual activities
      (OR: 1.6; IC 1.2-2.2; p<0.001), reporting lack of time to discuss SRH during
      service provision (OR: 1.7; IC 1.0-2.7; p<0.05), and insufficient openness among
      service providers to discuss SRH (OR: 2.0; IC 1.1-3.4; p<0.05). Other significant
      associations related to unmet support needs on safer sex practices (OR: 1.8; IC
      1.0-3.2; p<0.05), partner communication about sexuality (OR: 2.0; IC 1.1-3.4;
      p<0.05), and prevention of sexually transmitted infections (OR: 1.7; IC 1.0-3.0;
      p<0.05). Female gender had a protective effect (OR: 0.2; IC 0.0-0.9; p<0.05).
      Being denied the opportunity to discuss SRH may translate in feelings of
      discrimination. Improving health care providers' communication skills, and
      fostering openness about SRH topics in HIV care could contribute to
      destigmatization of PLHIV.

PMID- 24568695
TI  - Strategies to inhibit tumor associated integrin receptors: rationale for dual and
      multi-antagonists.
AB  - The integrins are a family of 24 heterodimeric transmembrane cell surface
      receptors. Involvement in cell attachment to the extracellular matrix, motility,
      and proliferation identifies integrins as therapeutic targets in cancer and
      associated conditions: thrombosis, angiogenesis, and osteoporosis. The most
      reported strategy for drug development is synthesis of an agent that is highly
      selective for a single integrin receptor. However, the ability of cancer cells to
      change their integrin repertoire in response to drug treatment renders this
      approach vulnerable to the development of resistance and paradoxical promotion of
      tumor growth. Here, we review progress toward development of antagonists
      targeting two or more members of the Arg-Gly-Asp (RGD) binding integrins, notably
      alphavbeta3, alphavbeta5, alphavbeta6, alphavbeta8, alpha5beta1, and
      alphaIIbbeta3, as anticancer therapeutics. 

PMID- 24568696
TI  - Highly enantioselective organocatalyzed vinylogous Michael-type reaction for the
      construction of trifluoromethylated all-carbon quaternary stereocenters.
AB  - The first example of a highly enantioselective vinylogous Michael-type reaction
      of beta,beta-disubstituted nitroalkenes is disclosed. A series of biologically
      important chiral oxindoles, featuring a trifluoromethylated all-carbon quaternary
      chiral center, were obtained in good yields with excellent enantioselectivities
      (up to >99% ee). 

PMID- 24568697
TI  - Using smart mobile devices in social-network-based health education practice: a
      learning behavior analysis.
AB  - Virtual communities provide numerous resources, immediate feedback, and
      information sharing, enabling people to rapidly acquire information and knowledge
      and supporting diverse applications that facilitate interpersonal interactions,
      communication, and sharing. Moreover, incorporating highly mobile and convenient
      devices into practice-based courses can be advantageous in learning situations.
      Therefore, in this study, a tablet PC and Google+ were introduced to a health
      education practice course to elucidate satisfaction of learning module and
      conditions and analyze the sequence and frequency of learning behaviors during
      the social-network-based learning process. According to the analytical results,
      social networks can improve interaction among peers and between educators and
      students, particularly when these networks are used to search for data, post
      articles, engage in discussions, and communicate. In addition, most nursing
      students and nursing educators expressed a positive attitude and satisfaction
      toward these innovative teaching methods, and looked forward to continuing the
      use of this learning approach. 

PMID- 24568698
TI  - Identifying clinical learning needs using structured group feedback: first year
      evaluation of pre-registration nursing and midwifery degree programmes.
AB  - BACKGROUND: Facilitating and supporting clinical learning for student nurses and
      midwives are essential within their practice environments. Clinical placements
      provide unique opportunities in preparation for future roles. Understanding the
      experiences of first year student nurses and midwives following clinical
      exposures and examining the clinical facilitators and barriers can assist in
      maintaining and developing clinical supports. METHODS: The study used a
      structured group feedback approach with a convenience sample of 223 first year
      nursing and midwifery students in one Irish university in April 2011 to ascertain
      feedback on the clinical aspects of their degree programme. RESULTS:
      Approximately 200 students participated in the process. Two key clinical issues
      were identified by students: facilitating clinical learning and learning
      experiences and needs. Positive learning environments, supportive staff and
      increased opportunities for reflection were important issues for first year
      students. CONCLUSIONS: The role of supportive mentoring staff in clinical
      practice is essential to enhance student learning. Students value reflection in
      practice and require more opportunities to engage during placements. More
      collaborative approaches are required to ensure evolving and adapting practice
      environments can accommodate student learning.

PMID- 24568699
TI  - Science to practice: why debate the role of Dbait for improving tumor ablation?
AB  - In this basic research study, Devun et al report an interesting set of
      experimental studies that document that adjuvant administration of Dbait, a DNA
      repair inhibitor, can be used to increase cytotoxicity of hyperthermia in in
      vitro cell lines and the effectiveness of tumor ablation from a given
      radiofrequency ablation application, including increased animal survival. The key
      novelty of this study lies in the use of this agent to take advantage of the
      ability of radiofrequency ablation to, at least temporarily, damage DNA. As such,
      the work has practical application and follows the line of study combining tumor
      ablation (and especially, the lower-dose reversible hyperthermia that surrounds a
      coagulated zone) with mechanism-based agents targeted to potentially reversible
      processes.

PMID- 24568701
TI  - New dogs, old tricks.

PMID- 24568702
TI  - US of the pediatric female pelvis.
AB  - This review presents the normal and pathologic development of the gonads and
      genitourinary tract and addresses the role of ultrasonography in the diagnosis
      and management of gynecologic disorders of the pediatric pelvis, including
      ambiguous genitalia, prepubertal bleeding, primary amenorrhea, pelvic mass, and
      pelvic pain.

PMID- 24568704
TI  - State of the art: Imaging of occupational lung disease.
AB  - Imaging of occupational lung disease, often perceived as a static discipline,
      continues to evolve with changes in industry and imaging technology. The
      challenge of accurately identifying an occupational exposure as the cause of lung
      disease demands a team approach, requiring integration of imaging features with
      exposure type, time course, and severity. Increasing use of computed tomography
      has demonstrated that specific occupational exposures can result in a variety of
      patterns of lung injury. The radiologist must understand the spectrum of expected
      imaging patterns related to known occupational exposures and must also recognize
      newly described occupational exposure risks, often related to recent changes in
      industrial practices.

PMID- 24568708
TI  - Case 203: Gorham disease.
AB  - A 77-year-old woman presented with pain in the right elbow of several years
      duration. There was no history of trauma, immunocompromise, or known malignancy.
      Blood chemistry tests revealed an alkaline phosphatase level of 93 U/L (1.6
      MUkat/L) (30-120 U/L [0.5-2.0 MUkat/L]), a sodium level of 139 mmol/L (135-147
      mmol/L), a potassium level of 4.4 mmol/L (3.4-5.0 mmol/L), a calcium level of
      2.38 mmol/L (2.2-2.55 mmol/L), a phosphate level of 1.81 mmol/L (0.85-1.5
      mmol/L), a C-reactive protein level of less than 5 mg/L (47.6 nmol/L), and an
      erythrocyte sedimentation rate of 41 mm/h (0-15 mm/h). Hematologic findings were
      normal. Imaging included plain film radiography, computed tomography (CT), and
      magnetic resonance (MR) imaging of the right humerus. Bone biopsies were obtained
      3 months and 4 years after initial presentation.

PMID- 24568709
TI  - Perfusion CT vascular parameters and microvessel density.

PMID- 24568710
TI  - Split-bolus spectral multidetector CT of the pancreas: problem solving in the
      detection of "isoattenuating" pancreatic cancer?

PMID- 24568711
TI  - Statistical sins of CIN (contrast material-induced nephropathy).

PMID- 24568715
TI  - Isothermal behavior of the Soret effect in nonionic microemulsions: size
      variation by using different n-alkanes.
AB  - In this work we investigate the thermodiffusion behavior of microemulsion
      droplets of the type H2O/n-alkane/C12E5 (pentaethylene glycol monododecyl ether)
      using the n-alkanes: n-octane, n-decane, n-dodecane, and n-tetradecane. In order
      to determine the thermodiffusion behavior of these microemulsion droplets, we
      apply the infrared thermal diffusion forced Rayleigh scattering (IR-TDFRS)
      technique. We measure the Soret coefficient (ST) as function of the structure
      upon approaching the emulsification failure boundary (efb) and as a function of
      the radius of the spherical o/w microemulsion droplets close to the efb. By
      varying the chain length of the n-alkanes, we are able to study the
      thermodiffusion behavior of spherical o/w microemulsion droplets of different
      sizes at the same temperature. In the investigated range a linear dependence of
      the Soret coefficient as function of the radius was found. By use of a proposed
      relationship between the Soret coefficient and the temperature dependence of the
      interfacial tension, the transition layer l could be determined for the first
      time. Additionally, small angle neutron scattering (SANS) experiments are
      performed to determine the size and to prove that the shape of the microemulsion
      droplets is spherical close to the efb. Accordingly, the scattering curves could
      be quantitatively described by a combination of a spherical core-shell form
      factor and sticky hard sphere structure factor. 

PMID- 24568703
TI  - Clinical proton MR spectroscopy in central nervous system disorders.
AB  - A large body of published work shows that proton (hydrogen 1 [(1)H]) magnetic
      resonance (MR) spectroscopy has evolved from a research tool into a clinical
      neuroimaging modality. Herein, the authors present a summary of brain disorders
      in which MR spectroscopy has an impact on patient management, together with a
      critical consideration of common data acquisition and processing procedures. The
      article documents the impact of (1)H MR spectroscopy in the clinical evaluation
      of disorders of the central nervous system. The clinical usefulness of (1)H MR
      spectroscopy has been established for brain neoplasms, neonatal and pediatric
      disorders (hypoxia-ischemia, inherited metabolic diseases, and traumatic brain
      injury), demyelinating disorders, and infectious brain lesions. The growing list
      of disorders for which (1)H MR spectroscopy may contribute to patient management
      extends to neurodegenerative diseases, epilepsy, and stroke. To facilitate
      expanded clinical acceptance and standardization of MR spectroscopy methodology,
      guidelines are provided for data acquisition and analysis, quality assessment,
      and interpretation. Finally, the authors offer recommendations to expedite the
      use of robust MR spectroscopy methodology in the clinical setting, including
      incorporation of technical advances on clinical units.

PMID- 24568716
TI  - Preparation of tethered-lipid bilayers on gold surfaces for the incorporation of
      integral membrane proteins synthesized by cell-free expression.
AB  - There is an increasing interest to express and study membrane proteins in vitro.
      New techniques to produce and insert functional membrane proteins into planar
      lipid bilayers have to be developed. In this work, we produce a tethered lipid
      bilayer membrane (tBLM) to provide sufficient space for the incorporation of the
      integral membrane protein (IMP) Aquaporin Z (AqpZ) between the tBLM and the
      surface of the sensor. We use a gold (Au)-coated sensor surface compatible with
      mechanical sensing using a quartz crystal microbalance with dissipation
      monitoring (QCM-D) or optical sensing using the surface plasmon resonance (SPR)
      method. tBLM is produced by vesicle fusion onto a thin gold film, using
      phospholipid-polyethylene glycol (PEG) as a spacer. Lipid vesicles are composed
      of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and 1,2-distearoyl-sn
      glycero-3-phosphoethanolamine-N-poly(ethyleneglycol)-2000-N-[3-(2
      pyridyldithio)propionate], so-called DSPE-PEG-PDP, at different molar ratios
      (respectively, 99.5/0.5, 97.5/2.5, and 95/5 mol %), and tBLM formation is
      characterized using QCM-D, SPR, and atomic force technology (AFM). We demonstrate
      that tBLM can be produced on the gold surface after rupture of the vesicles using
      an alpha helical (AH) peptide, derived from hepatitis C virus NS5A protein, to
      assist the fusion process. A cell-free expression system producing the E. coli
      integral membrane protein Aquaporin Z (AqpZ) is directly incubated onto the tBLMs
      for expression and insertion of the IMP at the upper side of tBLMs. The
      incorporation of AqpZ into bilayers is monitored by QCM-D and compared to a
      control experiment (without plasmid in the cell-free expression system). We
      demonstrate that an IMP such as AqpZ, produced by a cell-free expression system
      without any protein purification, can be incorporated into an engineered tBLM
      preassembled at the surface of a gold-coated sensor. 

PMID- 24568718
TI  - Averaging scheme for atomic resolution off-axis electron holograms.
AB  - All micrographs are limited by shot-noise, which is intrinsic to the detection
      process of electrons. For beam insensitive specimen this limitation can in
      principle easily be circumvented by prolonged exposure times. However, in the
      high-resolution regime several instrumental instabilities limit the applicable
      exposure time. Particularly in the case of off-axis holography the holograms are
      highly sensitive to the position and voltage of the electron-optical biprism. We
      present a novel reconstruction algorithm to average series of off-axis holograms
      while compensating for specimen drift, biprism drift, drift of biprism voltage,
      and drift of defocus, which all might cause problematic changes from exposure to
      exposure. We show an application of the algorithm utilizing also the
      possibilities of double biprism holography, which results in a high quality exit
      wave reconstruction with 75 pm resolution at a very high signal-to-noise ratio.

PMID- 24568719
TI  - Single, dual and multiple respiratory virus infections and risk of
      hospitalization and mortality.
AB  - Respiratory virus infections cause a significant number of hospitalization and
      deaths globally. This study investigated the association between single and
      multiple respiratory virus infections and risk of admission to a general ward,
      intensive care unit or death in patients aged 0-105 years (mean +/- s.d. = 24.4
      +/- 24.1 years), from North West England, that were tested for respiratory virus
      infections between January 2007 and June 2012. The majority of infections were in
      children aged ?5 years. Dual or multiple infections occurred in 10.4% (1214/11
      715) of patients, whereas single infection occurred in 89.6% (10 501/11 715).
      Rhinovirus was the most common co-infecting virus (occurring in 69.5%; 844/1214
      of co-infections). In a multivariate logistic regression model, multiple
      infections were associated with an increased risk of admission to a general ward
      [odds ratio (OR) 1.43, 95% confidence interval (CI) 1.2-1.7, P < 0.0001]. On the
      other hand, patients with respiratory syncytial virus (RSV) and human
      parainfluenza virus types 1-3 (hPIV1-3), as a single infection, had a higher risk
      of being admitted to a general ward (OR 1.49, 95% CI 1.28-1.73, P < 0.0001 and OR
      1.34, 95% CI 1.003-1.8, P = 0.05, respectively); admitted to an intensive-care
      unit or dying (OR 1.5, 95% CI 1.20-2.0, P = 0.001 and OR 1.60, 95% CI 1.02-2.40,
      P = 0.04, respectively). This result emphasizes the importance of RSV, hPIV and
      mixed infections and calls for research on vaccines, drugs and diagnostic tests
      targeting these respiratory viruses.

PMID- 24568717
TI  - Selected biomarkers as predictive tools in testing efficacy of melatonin and
      coenzyme Q on propionic acid - induced neurotoxicity in rodent model of autism.
AB  - BACKGROUND: Exposures to environmental toxins are now thought to contribute to
      the development of autism spectrum disorder. Propionic acid (PA) found as a
      metabolic product of gut bacteria has been reported to mimic/mediate the
      neurotoxic effects of autism. Results from animal studies may guide
      investigations on human populations toward identifying environmental contaminants
      that produce or drugs that protect from neurotoxicity. Forty-eight young male
      Western Albino rats were used in the present study. They were grouped into six
      equal groups 8 rats each. The first group received a neurotoxic dose of buffered
      PA (250 mg/Kg body weight/day for 3 consecutive days). The second group received
      only phosphate buffered saline (control group). The third and fourth groups were
      intoxicated with PA as described above followed by treatment with either coenzyme
      Q (4.5 mg/kg body weight) or melatonin (10 mg/kg body weight) for one week
      (therapeutically treated groups). The fifth and sixth groups were administered
      both compounds for one week prior to PA (protected groups). Heat shock protein70
      (Hsp70), Gamma amino-butyric acid (GABA), serotonin, dopamine, oxytocin and
      interferon gamma-inducible protein 16 together with Comet DNA assay were measured
      in brain tissues of the six studied groups. RESULTS: The obtained data showed
      that PA caused multiple signs of brain toxicity revealed in depletion of GABA,
      serotonin, and dopamine, are which important neurotransmitters that reflect brain
      function, interferon gamma-inducible protein 16 and oxytocin. A high significant
      increase in tail length, tail DNA% damage and tail moment was reported indicating
      the genotoxic effect of PA. Administration of melatonin or coenzyme Q showed both
      protective and therapeutic effects on PA-treated rats demonstrated in a
      remarkable amelioration of most of the measured parameters. CONCLUSION: In
      conclusion, melatonin and coenzyme Q have potential protective and restorative
      effects against PA-induced brain injury, confirmed by improvement in biochemical
      markers and DNA double strand breaks.

PMID- 24568720
TI  - Cataract surgery in patients with left ventricular assist device support.
AB  - Left ventricular assist devices (LVADs) have been increasingly used for 20 years
      in terminally ill patients with advanced heart failure or awaiting cardiac
      transplantation. Despite improvement in morbidity and mortality from use of these
      devices, quality of life may be limited by cataract. Access to cataract surgery
      in this predominantly elderly population is essential but limited by
      unfamiliarity with these devices. We describe phacoemulsification and intraocular
      lens implantation in 2 patients with LVADs. The patients had extensive
      preoperative cardiology evaluations and were instructed to continue warfarin
      through the day of surgery. Monitored sedation was used with fentanyl and
      midazolam. Both patients experienced significant improvement in visual acuity and
      quality of life. Neither experienced intraoperative hemodynamic instability.
      Cataract surgery may be safely performed in patients with LVAD support when
      adequate monitoring resources are available. FINANCIAL DISCLOSURE: No author has
      a financial or proprietary interest in any material or method mentioned.

PMID- 24568721
TI  - Change in keratometry after myopic laser in situ keratomileusis and
      photorefractive keratectomy.
AB  - PURPOSE: To compare the change in keratometry (K), spherical equivalent (SE), and
      visual acuity after myopic laser in situ keratomileusis (LASIK) and
      photorefractive keratectomy (PRK). SETTING: Academic tertiary care center.
      DESIGN: Retrospective review. METHODS: The postoperative K, SE, and uncorrected
      and corrected distance visual acuities were measured 6 months, 9 months, 1 year,
      2 years, 3 years, 4 to 5 years, 6 to 7 years, and 8+ years postoperatively. A
      difference (Delta) for each variable was calculated from its 6-month
      postoperative baseline. The rates of change were grouped based on the magnitude
      of myopic correction (0.00 to 2.99 diopters [D]; 3.00 to 5.99 D; 6.00 to 8.99 D),
      type of surgery (LASIK versus PRK), and age (<34 years; 34 to 45 years; >45
      years). RESULTS: Statistically significant differences were found in the rates of
      change between low and moderate corrections to high corrections for DeltaKavg
      (P=.0472 and P=.0091, respectively) and DeltaSE (both P<.0001). Statistically
      significant differences were found in the rate of change in DeltaKavg between all
      3 ages groups (P=.0330, P=.0051, and P<.0001) and in DeltaSE between ages less
      than 34 years and 34 to 45 years to ages over 45 years (P=.0158 and P=.0015,
      respectively). There was no significant difference in the rate of change in
      DeltaKavg and DeltaSE between LASIK and PRK (P=.3599 and P=.9403, respectively).
      CONCLUSION: There was keratometric and refractive regression for myopic LASIK,
      with the rate of regression depending on treatment magnitude and age. FINANCIAL
      DISCLOSURE: No author has a financial or proprietary interest in any material or
      method mentioned.

PMID- 24568722
TI  - Comparison of morphologic features of clear corneal incisions created with a
      femtosecond laser or a keratome.
AB  - PURPOSE: To compare the morphology of clear corneal incisions (CCIs) created with
      a femtosecond laser (Catalys) or a keratome (2.65 mm steel) during
      phacoemulsification using anterior segment optical coherence tomography (AS-OCT)
      and analyze the intended versus the achieved morphologic characteristics of
      femtosecond laser-generated CCIs. SETTING: Northwestern University Feinberg
      School of Medicine, Chicago, Illinois, USA. DESIGN: Comparative case series.
      METHODS: Eyes with femtosecond CCIs and age-matched eyes with the keratome CCIs
      underwent AS-OCT of the incisions 1 month after phacoemulsification. ImageJ
      software was used to evaluate AS-OCT images for CCI length, endothelial gaping,
      endothelial misalignment, and Descemet membrane detachment. RESULTS: In the
      femtosecond group (20 eyes) and keratome group (16 eyes), the mean values were
      CCI length, 1.99 mm+/-0.07 (SEM) versus 2.04+/-0.23 mm (P=.39); endothelial
      gaping, 0.14+/-0.03 mm versus 0.19+/-0.09 mm (P=.03); endothelial misalignment,
      0.04+/-0.03 mm versus 0.08+/-0.06 mm (P=.022). No eye in the femtosecond group
      and 3 eyes in the keratome group had a Descemet membrane detachment (P=.04). Six
      femtosecond eyes and 11 keratome eyes had posterior wound retraction (P=.02). The
      mean CCI length was 94.9% of the intended 2.1 mm, the posterior plane depth was
      93.3% of the intended 70%, and the posterior side-cut angle was 91.7% of the
      intended 45 degrees. CONCLUSION: Femtosecond laser-generated CCIs had
      significantly lower endothelial gaping, endothelial misalignment, Descemet
      membrane detachment, and posterior wound retraction than keratome-created CCIs
      and were within 10% of the intended length, depth, and angle measurements.
      FINANCIAL DISCLOSURE: Neither author has a financial or proprietary interest in
      any material or method mentioned.

PMID- 24568723
TI  - Effect of the eyelid speculum on pachymetry during corneal collagen crosslinking
      in keratoconus patients.
AB  - PURPOSE: To compare central corneal thickness (CCT) with and without using an
      eyelid speculum during corneal collagen crosslinking (CXL). SETTING: University
      Medical Center Utrecht, Utrecht, the Netherlands. DESIGN: Prospective
      nonrandomized comparative study. METHODS: Eyes with progressive keratoconus were
      treated by CXL and consecutively divided into 2 groups. In Group A, an eyelid
      speculum remained in place throughout the entire CXL procedure. In Group B, the
      eyelids remained closed during the 30-minute riboflavin instillation.
      Intraoperative ultrasound pachymetry measurements were performed at different
      timepoints. The visual acuity, refraction, keratometry, pachymetry, and
      endothelium were evaluated 6 months after CXL. The main outcome measures were
      intraoperative CCT measurements and the clinical CXL effect after 6 months.
      RESULTS: Fifty-two eyes (50 patients) were treated. After riboflavin
      instillation, a statistically significant difference in CCT reduction was found
      between the 2 groups (P<.001), with a mean CCT decrease of 62 MUm+/-53 (SD)
      (13%+/-11%) in Group A and 11+/-35 MUm (2%+/-8%) in Group B. No statistically
      significant between-group differences were found after epithelial removal or
      ultraviolet-A (UVA) irradiation. Six months after CXL, no statistically
      significant between-group difference was found in the visual acuity, refraction,
      keratometry, pachymetry, or endothelium. CONCLUSIONS: Avoidance of an eyelid
      speculum during riboflavin instillation resulted in less CCT reduction during
      CXL. This finding could increase the chance of attaining the required pachymetry
      safety margin for applying UVA and thus decrease the chance of premature CXL
      treatment termination. FINANCIAL DISCLOSURE: No author has a financial or
      proprietary interest in any material or method mentioned.

PMID- 24568724
TI  - Awareness of intraoperative floppy-iris syndrome among primary care physicians.

PMID- 24568726
TI  - Instantaneous generation of charge-separated state on TiO2 surface sensitized
      with plasmonic nanoparticles.
AB  - Photoexcitation of the plasmon band in metallic nanoparticles adsorbed on a TiO2
      surface initiates many important photovoltaic and photocatalytic processes. The
      traditional view on the photoinduced charge separation involves excitation of a
      surface plasmon, its subsequent dephasing into electron-hole pairs, followed by
      electron transfer (ET) from the metal nanoparticle into TiO2. We use nonadiabatic
      molecular dynamics combined with time-domain density functional theory to
      demonstrate that an electron appears inside TiO2 immediately upon photoexcitation
      with a high probability (~50%), bypassing the intermediate step of electron-hole
      thermalization inside the nanoparticle. By providing a detailed, atomistic
      description of the charge separation, energy relaxation, and electron-hole
      recombination processes, the simulation rationalizes why the experimentally
      observed ultrafast photoinduced ET in an Au-TiO2 system is possible in spite of
      the fast energy relaxation. The simulation shows that the photogenerated plasmon
      is highly delocalized onto TiO2, and thus, it is shared by the electron donor and
      acceptor materials. In the 50% of the cases remaining after the instantaneous
      photogeneration of the charge-separated state, the electron injects into TiO2 on
      a sub-100 fs time scale by the nonadiabatic mechanism due to high density of
      acceptor states. The electron-phonon relaxation parallels the injection and is
      slower, resulting in a transient heating of the TiO2 surface by 40 K. Driven by
      entropy, the electron moves further into TiO2 bulk. If the electron remains
      trapped at the TiO2 surface, it recombines with the hole on a picosecond time
      scale. The obtained ET and recombination times are in excellent agreement with
      the experiment. The delocalized plasmon state observed in our study establishes a
      novel concept for plasmonic photosensitization of wide band gap semiconductors,
      leading to efficient conversion of photons to charge carriers and to hybrid
      materials with a wide variety of applications in photocatalysis and
      photovoltaics.

PMID- 24568725
TI  - Delayed presentation of retained nuclear fragment following phacoemulsification
      cataract extraction.
AB  - An 87-year-old woman presented 11 months after routine phacoemulsification
      cataract extraction and posterior chamber intraocular lens implantation in her
      left eye complaining of the abrupt onset of redness and decreased vision in that
      eye. Examination revealed a mild anterior chamber reaction and significant
      corneal edema. The eye was minimally responsive to topical steroid therapy, and
      initial serial slitlamp examinations with gonioscopy were unrevealing. After
      multiple head-positioning maneuvers were performed, a retained nuclear fragment
      was uncovered. The nuclear fragment was aspirated and liquefied by the
      phacoemulsification device in the anterior chamber. A retained nuclear fragment
      with an intact posterior capsule is a recognized cause of inflammation in the
      immediate postoperative presentation. Delayed presentation of symptoms is rare
      and presumably secondary to sequestration of the fragment behind the iris. We
      present a case and a review of the literature regarding sequestered retained
      nuclear fragments following what is initially thought to be uneventful cataract
      extraction. FINANCIAL DISCLOSURE: No author has a financial or proprietary
      interest in any material or method mentioned.

PMID- 24568727
TI  - Difficulty of patient selection in a combined heart-kidney transplant: a case
      report.
AB  - Combined heart-kidney transplant has become an alternative for heart transplant
      candidates with significant chronic kidney disease. However, it is not clear
      which patients will benefit most from such intervention, and in whom cardiac
      transplant alone will be sufficient to restore adequate renal function. We report
      the case of a man with ischemic cardiomyopathy and chronic kidney disease who was
      wait-listed for heart-kidney transplant after acute decompensated heart failure
      and renal failure requiring hemodialysis. Because of unexpected circumstances,
      the kidney transplant was cancelled, and only a heart transplant was performed.
      Nonetheless, the kidney function rapidly improved beyond the levels before
      hospitalization and remains stable months after transplant. This case illustrates
      the difficulties in assessing the reversibility of kidney damage in the context
      of heart failure requiring transplant. This issue is primordial to improve
      selection of patients who will benefit most from combined heart-kidney transplant
      in a context of scarce organ allocation resources. 

PMID- 24568728
TI  - Microwave hydrothermal transformation of amorphous calcium carbonate nanospheres
      and application in protein adsorption.
AB  - Calcium carbonate and calcium phosphate are the main components of biominerals.
      Among all of the forms of biominerals, amorphous calcium carbonate (ACC) and
      amorphous calcium phosphate (ACP) are the most important forms because they play
      a pivotal role in the process of biomineralization and are the precursors to the
      crystalline polymorphs. In this work, we first synthesized ACC in vitro using
      adenosine 5'-triphosphate disodium salt (ATP) as the stabilizer and investigated
      the transformation of the ACC under microwave hydrothermal conditions, and
      ACC/ACP composite nanospheres and carbonated hydroxyapatite (CHA) nanospheres
      were successfully prepared. In this novel strategy, ATP has two main functions:
      it serves as the stabilizer for ACC and the phosphorus source for ACP and CHA.
      Most importantly, the morphology and the size of the ACC precursor can be well
      preserved after microwave heating, so it provides a new method for the
      preparation of calcium phosphate nanostructured materials using phosphorus
      containing biomolecule-stabilized ACC as the precursor. Furthermore, the as
      prepared ACC/ACP composite nanospheres have excellent biocompatibility and high
      protein adsorption capacity, indicating that they are promising for applications
      in biomedical fields such as drug delivery and protein adsorption. 

PMID- 24568729
TI  - Implementation of a quality improvement program to improve sweat test performance
      in a pediatric hospital.
AB  - CONTEXT: All positive screening of newborns for cystic fibrosis using the dried
      blood spot 2-tiered immunoreactive trypsinogen/DNA method requires subsequent
      sweat chloride testing for confirmation. Obtaining an adequate volume of sweat to
      measure chloride is a challenge for many cystic fibrosis centers across the
      nation. The standard for patients older than 3 months is less than 5% quantity
      not sufficient (QNS) and for patients 3 months or younger is less than 10% QNS.
      OBJECTIVE: To set up a quality improvement (QI) program for sweat testing to
      improve QNS rates using the Wescor Macroduct (Wescor, Inc, Logan, Utah) method at
      Texas Children's Hospital's laboratory, Houston, Texas. DESIGN: Single-center
      study. RESULTS: Quantity not sufficient rates were evaluated for 4 months before
      and 8 months after implementation of the QI program for patients aged 3 months or
      younger and those older than 3 months. The QI program included changes in
      technician training, service, site of collection, mode of collection, weekly
      review, and forms to screen patients for medications that may alter sweat
      production. A marked improvement was observed in the rates of QNS, which declined
      considerably from 16.7% to 8.5% (<=3 months old) and from 9.3% to 2.2% (>3 months
      old) after implementation of the QI initiative in both age categories.
      CONCLUSION: This report demonstrates the effectiveness of the QI program in
      significantly improving QNS rates in sweat chloride testing in a pediatric
      hospital.

PMID- 24568730
TI  - Functional role of Barrington's nucleus in the micturition reflex: relevance in
      the surgical treatment of Parkinson's disease.
AB  - The pontine micturition center or Barrington's nucleus (BN) - besides regulating
      micturition - co-regulates the activity of other pelvic viscera such as the colon
      and genitals. At present, this issue is gaining particular importance due to: (i)
      recent findings of alpha-synuclein in BN, (ii) known urinary dysfunction in
      parkinsonian patients (part of the so-called non-motor symptoms), other patients
      with dementia and as in very old individuals; and (iii) its proximity to the
      pedunculopontine nucleus, a surgical target in deep brain stimulation for
      Parkinson's disease (PD). The structural and functional organization of the
      micturition reflex comprises a coordinating action of somatic motor activity with
      both divisions of the autonomic nervous system, modulated by trunk encephalic and
      cortical centers that involve the BN as locus coeruleus and periaqueductal gray
      matter, among other trunk encephalic structures. The involvement of dopaminergic
      activity (physiologic inhibition of the micturition reflex mediated by
      dopaminergic D1 activity) that diminishes in Parkinsonism and leads to
      overactivity of the micturition reflex is also well known. In this review, the
      integrating role of the BN in the context of vesical and gastrointestinal
      behavior is revisited, and the principal morpho-functional findings that
      associate dysfunction with the urinary disorders that appear during the pre-motor
      stages of PD are summarized. 

PMID- 24568731
TI  - Maintenance of the large-scale depolarization wave in the embryonic chick brain
      against deprivation of the rhythm generator.
AB  - Widely correlated spontaneous activity in the developing nervous system is
      transiently expressed and is considered to play a fundamental role in neural
      circuit formation. The depolarization wave, which spreads over a long distance
      along the neuraxis, maximally extending to the lumbosacral cord and forebrain, is
      an example of this spontaneous activity. Although the depolarization wave is
      typically initiated in the spinal cord in intact preparations, spontaneous
      discharges have also been detected in the isolated brainstem. Although this
      suggests that the brainstem has the ability to generate spontaneous activity, but
      is paced by a caudal rhythm generator of higher excitability, a number of
      questions remains. Does brainstem activity simply appear as a passive
      consequence, or does any active change occur in the brainstem network to
      compensate for this activity? If the latter is the case, does this compensation
      occur equally at different developmental stages? Where is the new rhythm
      generator in the isolated brainstem? To answer these questions, we optically
      analyzed spatio-temporal patterns of activity detected from the chick brainstem
      before and after transection at the obex. The results revealed that the
      depolarization wave was homeostatically maintained, which was characterized by an
      increase in excitability and/or the number of neurons recruited to the wave. The
      wave was more easily maintained in younger embryos. Furthermore, we demonstrated
      that the ability of brainstem neurons to perform such an active compensation was
      not lost even at the stage when the depolarization wave was no longer observed in
      the intact brainstem. 

PMID- 24568732
TI  - Age-dependent effects of valproic acid in Alzheimer's disease (AD) mice are
      associated with nerve growth factor (NGF) regulation.
AB  - Alzheimer's disease (AD) is a progressive neurodegenerative disease that causes
      cognitive impairment. Major pathophysiological AD characteristics include
      numerous senile plaque, neurofibrillary tangles, and neuronal loss in the
      specific regions of patients' brains. In this study, we aimed to understand
      disease stage-dependent regulation of histone modification for the expression of
      specific markers in plasma and the hippocampus of in vivo AD model. Since the
      control of histone acetylation/deacetylation has been studied as one of major
      epigenetic regulatory mechanisms for specific gene expression, we detected the
      effects of histone deacetylase (HDAC) inhibitor on marker expression and
      neuroprotection in in vivo AD model mice. We determined the effects of valproic
      acid (VPA, HDAC inhibitor), on the levels of cytokines, secreted form of APP
      (sAPP), nerve growth factor (NGF), and cognitive function in Tg6799 AD mice in
      three different disease stages (1month: pre-symptomatic; 5months: early
      symptomatic; and 10months: late-symptomatic stages). VPA decreased the mRNA
      levels of nuclear factor kappaB (NF-kappaB) and IL-1beta in the plasma of Tg6799
      mice compared to vehicle control at 10months of age. VPA increased the protein
      levels of NGF in the hippocampus of Tg6799 mice at 5 and 10months of age. In
      addition, VPA decreased escape latencies of Tg6799 mice at 5 and 10months of age
      in Morris water maze assessment. Taken together, HDAC inhibition is a promising
      therapeutic target for AD and it needs to be considered in an age-dependent
      and/or stage-dependent manner. 

PMID- 24568733
TI  - Myocardial revascularization strategies in diabetic patients with multi-vessel
      disease: CABG vs DES-based PCI.
AB  - Randomized trials comparing multi-vessel percutaneous coronary intervention to
      coronary artery bypass grafting (CABG) have demonstrated the long-term
      superiority of CABG in diabetic patients. Benefits include improved survival,
      fewer recurrent myocardial infarctions and a lower risk of the need for repeat
      intervention. The focus of this review article is to review the contemporary
      management of diabetic patients with multi-vessel coronary artery disease. 

PMID- 24568734
TI  - The role of plain radiography in predicting renal stone fragmentation by
      shockwave lithotripsy in the era of noncontrast multidetector computed
      tomography.
AB  - PURPOSE: The objective of this study is to determine if plain radiography has a
      role in prediction of stone fragmentation by shockwave lithotripsy (SWL).
      PATIENTS AND METHODS: Our study included 106 patients undergoing SWL for renal
      stones. Based on plain radiography criteria, stones were classified according to
      density, homogeneity, and outline. We compared the success of SWL in
      fragmentation of stones with a density equal to or less than bone, nonhomogeneous
      stones, and stones with irregular outline to its success in stones with a density
      more than bone, homogeneous stones, and stones with smooth outline. RESULTS: In
      plain radiography, stone density equal to or less than bone, nonhomogeneous
      stones, and stones with irregular outline showed successful SWL fragmentation in
      88.8%, 91.2%, and 90.6%, respectively. Stones with a density more than bone,
      homogeneous stones, and stones with smooth outline showed successful SWL
      fragmentation in 52.9%, 52.6%, and 57.1%, respectively. CT attenuation value was
      significantly less in stones successfully fragmented by SWL compared with
      nonfragmented stone (649+/-169 and 1465+/-256, respectively). In homogeneous
      stones with smooth outline having a density more than bone, we found a
      significantly lower CT attenuation in patients with successful stone
      fragmentation by SWL compared with those with failed stone fragmentation (690.9+/
      171 and 1462+/-212, respectively). CONCLUSION: In relatively large solitary renal
      pelvic stones, plain radiography can predict the success of stone fragmentation
      by SWL. Nonhomogeneous stones with irregular outline and a density equal to or
      less than bone are expected to be successfully fragmented by SWL. Noncontrast CT
      is only needed, to predict success of SWL, in cases of homogeneous stones with
      smooth outline and density more than bone.

PMID- 24568735
TI  - Mode of action and clinical studies with fumarates in multiple sclerosis.
AB  - Multiple sclerosis (MS) as a chronic neuro-inflammatory and neurodegenerative
      disease of the central nervous system is frequently associated with severe
      disability and impairment in quality of life. Early disease-modifying treatment
      options have mainly focused on inflammatory aspects of the disease. Recently, the
      neurodegenerative features have received more attention in experimental models,
      paraclinical assessments and the evaluation of drug effects. Fumaric acid esters
      (FAEs) as orally available immunomodulatory and neuroprotective compounds have
      thus advanced to a highly interesting MS treatment option. Here, we will review
      the pharmaceutical history of FAEs, their immunomodulatory and putative
      neuroprotective mechanisms of action and clinical trial data in relapsing MS.

PMID- 24568736
TI  - Improved cross validation of a static ubiquitin structure derived from high
      precision residual dipolar couplings measured in a drug-based liquid crystalline
      phase.
AB  - The antibiotic squalamine forms a lyotropic liquid crystal at very low
      concentrations in water (0.3-3.5% w/v), which remains stable over a wide range of
      temperature (1-40  degrees C) and pH (4-8). Squalamine is positively charged, and
      comparison of the alignment of ubiquitin relative to 36 previously reported
      alignment conditions shows that it differs substantially from most of these, but
      is closest to liquid crystalline cetyl pyridinium bromide. High precision
      residual dipolar couplings (RDCs) measured for the backbone (1)H-(15)N, (15)N
      (13)C', (1)H(alpha)-(13)C(alpha), and (13)C'-(13)C(alpha) one-bond interactions
      in the squalamine medium fit well to the static structural model previously
      derived from NMR data. Inclusion into the structure refinement procedure of these
      RDCs, together with (1)H-(15)N and (1)H(alpha)-(13)C(alpha) RDCs newly measured
      in Pf1, results in improved agreement between alignment-induced changes in (13)C'
      chemical shift, (3)JHNHalpha values, and (13)C(alpha)-(13)C(beta) RDCs and
      corresponding values predicted by the structure, thereby validating the high
      quality of the single-conformer structural model. This result indicates that
      fitting of a single model to experimental data provides a better description of
      the average conformation than does averaging over previously reported NMR-derived
      ensemble representations. The latter can capture dynamic aspects of a protein,
      thus making the two representations valuable complements to one another. 

PMID- 24568737
TI  - Inhibition of TNF receptor signaling by anti-TNFalpha biologicals primes naive
      CD4(+) T cells towards IL-10(+) T cells with a regulatory phenotype and function.
AB  - TNFalpha is a potent pro-inflammatory cytokine playing a pivotal role in several
      autoimmune diseases. Little is known about the mechanism of TNFalpha blocking
      agents on naive T cell differentiation. Here, we report that neutralizing
      TNFalpha during priming of naive CD4(+) T cells by dendritic cells favors
      development of IL-10(+) T helper cells. TNFalpha counteracts IL-10(+) T cell
      priming mainly via TNFRI receptor signaling. While initial T cell activation was
      not affected, neutralization of TNFalpha negatively affected sustained T cell
      differentiation in later stages of T cell priming. Whole genome gene expression
      analysis revealed an extended regulatory gene profile for anti-TNFalpha-treated T
      cells. Indeed, neutralizing TNFalpha during naive T cell priming enhanced the
      suppressive function of anti-TNFalpha-treated T cells. Taken together, inhibition
      of TNFalpha-TNFR interaction shifts the balance of Th cell differentiation
      towards IL-10 expressing suppressive T cells, which may be one of the beneficial
      mechanisms in TNFalpha blocking therapies. 

PMID- 24568738
TI  - Aging-induced chemical and morphological modifications of thin film iron oxide
      electrodes for lithium-ion batteries.
AB  - Spectroscopic (XPS, ToF-SIMS) and microscopic (SEM, AFM) analytical methods have
      been applied to iron oxide (~Fe2O3) using a thin film approach to bring new
      insight into the aging mechanisms of conversion-type anode materials for lithium
      ion batteries. The results show that repeated lithiation/delithiation causes both
      chemical and morphological modifications affecting the electrochemical
      performance. The SEI layer formed by reductive decomposition of the electrolyte
      remains stable in composition (mostly Li2CO3) but irreversibly thickens upon
      multicycling. Irreversible swelling of the material accompanied by penetration of
      the SEI layer and accumulation of non-deconverted material in the bulk of the
      oxide thin film occurs upon repeated conversion/deconversion. After initial
      pulverization of the thin film microstructure, grain growth and aggregation are
      promoted by multicycling. This leads to capacity increase in the first few
      cycles, but upon further cycling volume expansion and accumulation of non
      deconverted material lead to deterioration of the electrode performances. 

PMID- 24568741
TI  - Self-reported availability of kinship cues during childhood is associated with
      kin-directed behavior to parents in adulthood.
AB  - Reliable recognition of kin is an important factor in modulating kin-directed
      behaviors. For example, in selectively directing cooperative behavior to kin and
      diverting sexual interest away from them, kin first need to be recognized as
      such. Although an increasing number of studies have examined what information is
      employed in recognizing siblings and children, less is known about the
      information children employ in identifying their parents. In a web-based survey,
      we asked 702 Finnish undergraduate and graduate students to report the
      availability of a number of possible kinship cues during their childhood and
      youth. After factorization of the responses, we found that the reported amount of
      parental support, phenotypic similarity, and behavioral similarity generally
      predicted subjective certainty in relatedness and kin-directed behavior (i.e.,
      cooperative behavior and inbreeding aversion) to parents in adulthood. Although
      the data suffer from their retrospective nature, the present study provides
      potentially useful information about kin-recognition of parents.

PMID- 24568742
TI  - The DSM-5 dissociative-PTSD subtype: can levels of depression, anxiety,
      hostility, and sleeping difficulties differentiate between dissociative-PTSD and
      PTSD in rape and sexual assault victims?
AB  - The DSM-5 currently includes a dissociative-PTSD subtype within its nomenclature.
      Several studies have confirmed the dissociative-PTSD subtype in both American
      Veteran and American civilian samples. Studies have begun to assess specific
      factors which differentiate between dissociative vs. non-dissociative PTSD. The
      current study takes a novel approach to investigating the presence of a
      dissociative-PTSD subtype in its use of European victims of sexual assault and
      rape (N=351). Utilizing Latent Profile Analyses, we hypothesized that a discrete
      group of individuals would represent a dissociative-PTSD subtype. We additionally
      hypothesized that levels of depression, anger, hostility, and sleeping
      difficulties would differentiate dissociative-PTSD from a similarly severe form
      of PTSD in the absence of dissociation. Results concluded that there were four
      discrete groups termed baseline, moderate PTSD, high PTSD, and dissociative-PTSD.
      The dissociative-PTSD group encompassed 13.1% of the sample and evidenced
      significantly higher mean scores on measures of depression, anxiety, hostility,
      and sleeping difficulties. Implications are discussed in relation to both
      treatment planning and the newly published DSM-5. 

PMID- 24568743
TI  - Lack of support for staff to combat racism.

PMID- 24568745
TI  - Acute estradiol treatment affects the expression of cocaine-induced conditioned
      place preference in ovariectomized female rats.
AB  - Women and female rodents are more responsive to the subjective effects of
      psychostimulant drugs of abuse compared to males. A growing body of literature
      supports a role for estradiol as a mechanism underlying these sex differences.
      However, little is known about the influence of acute elevations in levels of
      estradiol on drug conditioned behaviors. The aim of the present study was to
      evaluate the influence of an acute increase in systemic estradiol levels on the
      expression of cocaine conditioned place preference (CPP). Using a six day
      conditioning procedure, ovariectomized (OVX) female rats were conditioned with
      one of four doses of cocaine (2.5, 5, 10, or 15mg/kg) to associate one of two
      large chambers of a CPP apparatus with cocaine or saline. Thirty minutes prior to
      the start of the CPP preference test, rats were pretreated with either 5MUg
      estradiol benzoate (EB) or peanut oil (PO). PO-treated rats expressed a
      significant preference for only the mid-range conditioning doses of cocaine (5
      and 10mg/kg). However, acute EB treatment resulted in a rightward shift in the
      cocaine dose-response curve; rats demonstrated a significant preference at only
      the moderate and high conditioning doses of cocaine (10 and 15mg/kg). These
      findings demonstrate that acute elevations in estradiol may dampen the expression
      of conditioned responses to cocaine's secondary rewards at lower conditioning
      doses of the drug and facilitate CPP at higher doses while estradiol deficiency
      decreases the threshold dose of cocaine necessary to induce CPP.

PMID- 24568740
TI  - Optical mapping of sarcoplasmic reticulum Ca2+ in the intact heart: ryanodine
      receptor refractoriness during alternans and fibrillation.
AB  - RATIONALE: Sarcoplasmic reticulum (SR) Ca(2+) cycling is key to normal excitation
      contraction coupling but may also contribute to pathological cardiac alternans
      and arrhythmia. OBJECTIVE: To measure intra-SR free [Ca(2+)] ([Ca(2+)]SR) changes
      in intact hearts during alternans and ventricular fibrillation (VF). METHODS AND
      RESULTS: Simultaneous optical mapping of Vm (with RH237) and [Ca(2+)]SR (with
      Fluo-5N AM) was performed in Langendorff-perfused rabbit hearts. Alternans and VF
      were induced by rapid pacing. SR Ca(2+) and action potential duration (APD)
      alternans occurred in-phase, but SR Ca(2+) alternans emerged first as cycle
      length was progressively reduced (217+/-10 versus 190+/-13 ms; P<0.05). Ryanodine
      receptor (RyR) refractoriness played a key role in the onset of SR Ca(2+)
      alternans, with SR Ca(2+) release alternans routinely occurring without changes
      in diastolic [Ca(2+)]SR. Sensitizing RyR with caffeine (200 MUmol/L)
      significantly reduced the pacing threshold for both SR Ca(2+) and APD alternans
      (188+/-15 and 173+/-12 ms; P<0.05 versus baseline). Caffeine also reduced the
      magnitude of spatially discordant SR Ca(2+) alternans, but not APD alternans, the
      pacing threshold for discordance, or threshold for VF. During VF, [Ca(2+)]SR was
      high, but RyR remained nearly continuously refractory, resulting in minimal SR
      Ca(2+) release throughout VF. CONCLUSIONS: In intact hearts, RyR refractoriness
      initiates SR Ca(2+) release alternans that can be amplified by diastolic
      [Ca(2+)]SR alternans and lead to APD alternans. Sensitizing RyR suppresses
      spatially concordant but not discordant SR Ca(2+) and APD alternans. Despite
      increased [Ca(2+)]SR during VF, SR Ca(2+) release was nearly continuously
      refractory. This novel method provides insight into SR Ca(2+) handling during
      cardiac alternans and arrhythmia.

PMID- 24568746
TI  - T cell-specific BLIMP-1 deficiency exacerbates experimental autoimmune
      encephalomyelitis in nonobese diabetic mice by increasing Th1 and Th17 cells.
AB  - Recently, we demonstrated that B lymphocyte-induced maturation protein 1 (BLIMP
      1) has a role in regulating the differentiation and effector function of Th1 and
      Th17 cells. As these cells play critical roles in the induction and pathogenesis
      of experimental autoimmune encephalomyelitis (EAE), we investigated the potential
      role of T cell BLIMP-1 in modulating MOG35-55-induced EAE. We established T cell
      specific BLIMP-1 conditional knockout (CKO) NOD mice to dissect the role of BLIMP
      1 in EAE using loss-of-function model. Our results indicate that EAE severity is
      dramatically exacerbated in CKO mice. The numbers of CNS-infiltrating Th1, Th17,
      IFN-gamma(+)IL-17A(+), and IL-21(+)IL-17A(+) CD4(+) T cells are remarkably
      increased in brain and spinal cord of CKO mice. Moreover, the ratio of
      Tregs/effectors and IL-10 production of Tregs are significantly downregulated in
      CNS of CKO mice. We conclude that BLIMP-1 suppresses autoimmune encephalomyelitis
      via downregulating Th1 and Th17 cells and impairing Treg cells. 

PMID- 24568747
TI  - Characterization of organochlorine pesticides, brominated flame retardants and
      dioxin-like compounds in shellfish and eel from Fiji.
AB  - This article gives an overview of a range of persistent organic pollutant
      chemical levels in shellfish (Batissa violacea and Anadara antiquata) species and
      eel (Gymnothorax flavimarginatus) from Fiji. As there is limited data in
      published literature to date, this paper reports first data on a range of
      persistent organic pollutants and highlights the more prominent POP chemicals
      present in marine biota in Fiji. A significant number of POP chemicals were
      detected (e.g. 17 PCDD/PCDF, 12dl-PCBs, organochlorine pesticides and brominated
      flame retardants), the concentrations found were generally low (e.g. parts per
      billion level). The low levels of contamination are indicative of a low input
      from long range and short-range transport as well as few local point sources.
      Also concentrations of POPs in eel and shellfish from Fiji are low in comparison
      to wild species in other regions and are within acceptable limits for POP
      chemicals in fish and fishery products set by the European Union. It describes
      also results of early studies on basic POPs levels in shellfish in several
      Pacific Island Countries, which generally show relatively low levels. 

PMID- 24568748
TI  - Emissions and fate of brominated flame retardants in the indoor environment: a
      critical review of modelling approaches.
AB  - This review explores the existing understanding and the available approaches to
      estimating the emissions and fate of semi-volatile organic compounds (SVOCs) and
      in particular focuses on the brominated flame retardants (BFRs). Volatilisation,
      an important emission mechanism for the more volatile compounds can be well
      described using current emission models. More research is needed, however, to
      better characterise alternative release mechanisms such as direct material
      particle partitioning and material abrasion. These two particle-mediated
      emissions are likely to result in an increased chemical release from the source
      than can be accounted for by volatilisation, especially for low volatile
      compounds, and emission models need to be updated in order to account for these.
      Air-surface partitioning is an important fate process for SVOCs such as BFRs
      however it is still not well characterised indoors. In addition, the assumption
      of an instantaneous air-particle equilibrium adopted by current indoor fate
      models might not be valid for high-molecular weight, strongly sorbing compounds.
      A better description of indoor particle dynamics is required to assess the effect
      of particle-associated transport as this will control the fate of low volatile
      BFRs. We suggest further research steps that will improve modelling precision and
      increase our understanding of the factors that govern the indoor fate of a wide
      range of SVOCs. It is also considered that the appropriateness of the selected
      model for a given study relies on the individual characteristics of the study
      environment and scope of the study. 

PMID- 24568749
TI  - Whats that noise? Bedside monitoring in the Emergency Department.
AB  - OBJECTIVE: To determine the frequency, duration and type of audible monitor
      alarms in an ED, utilising the standard manufacturer's classification. METHODS:
      The audible monitor alarms and the timing of any intervention related to the
      patient monitoring was observed and recorded. RESULTS: 110 Patients admitted to
      the Majors area or Resuscitation Room were observed for a total of 93 hours. One
      monitor was observed at a time. Alarm noise was generated 29% of the observation
      time. Overall, 429 alarms lasting 21 hours 27 minutes were judged to be positive
      and 143 alarms lasting 5 hours 47 minutes, negative. 74% of Resuscitation Room
      and 47% of Majors alarms were silenced or paused. Alarm limit parameters were
      only adjusted after 5% of alarms in Resuscitation Room and 6% of alarms in
      Majors. CONCLUSIONS: Whilst high level monitoring is desired from a patient
      safety perspective, it contributes to a significant ambient noise level, which is
      recognised by all who pass through an ED, and can be detrimental to patients,
      relatives and staff. We have demonstrated that there is a high probability of
      near-continuous alarm noise from patient monitoring in a 10-bedded Majors area.
      We make suggestions for methods of noise reduction and intend to implement some
      of these within our own ED.

PMID- 24568750
TI  - Interface between metabolic balance and reproduction in ruminants: focus on the
      hypothalamus and pituitary.
AB  - This article is part of a Special Issue "Energy Balance". The interface between
      metabolic regulators and the reproductive system is reviewed with special
      reference to the sheep. Even though sheep are ruminants with particular metabolic
      characteristics, there is a broad consensus across species in the way that the
      reproductive system is influenced by metabolic state. An update on the
      neuroendocrinology of reproduction indicates the need to account for the way that
      kisspeptin provides major drive to gonadotropin releasing hormone (GnRH) neurons
      and also mediates the feedback effects of gonadal steroids. The way that
      kisspeptin function is influenced by appetite regulating peptides (ARP) is
      considered. Another newly recognised factor is gonadotropin inhibitory hormone
      (GnIH), which has a dual function in that it suppresses reproductive function
      whilst also acting as an orexigen. Our understanding of the regulation of food
      intake and energy expenditure has expanded exponentially in the last 3 decades
      and historical perspective is provided. The function of the regulatory factors
      and the hypothalamic cellular systems involved is reviewed with special reference
      to the sheep. Less is known of these systems in the cow, especially the dairy
      cow, in which a major fertility issue has emerged in parallel with selection for
      increased milk production. Other endocrine systems--the hypothalamo-pituitary
      adrenal axis, the growth hormone (GH) axis and the thyroid hormones--are
      influenced by metabolic state and are relevant to the interface between metabolic
      function and reproduction. Special consideration is given to issues such as
      season and lactation, where the relationship between metabolic hormones and
      reproductive function is altered.

PMID- 24568752
TI  - Vibrational spectroscopy of small hydrated CuOH+ clusters.
AB  - Coordinated copper hydroxide centers can play an important role in copper
      catalyzed water oxidation reactions. To have a better understanding of the
      interactions involved in these complexes, we studied the vibrational spectra of
      D2 tagged CuOH(+)(H2O)n clusters in the OH stretch region. These clusters are
      generated by electrospray ionization and probed via cryogenic ion vibrational
      spectroscopy. The results show that the copper center in the n = 3 clusters has a
      distorted square planar geometry. The coordination in CuOH(+)(H2O)n is therefore
      more akin to Cu(2+)(H2O)n with four ligands in the first solvation shell than
      Cu(+)(H2O)n with two ligands in the first solvation shell. There is also no
      evidence of any strong axial ligand interactions. The well-resolved experimental
      spectra enabled us to point out some discrepancies in the calculated spectra,
      which were found to be highly dependent on the level of theory used. 

PMID- 24568751
TI  - Reduction of bodily pain in response to an online positive activities
      intervention.
AB  - Inducing temporary positive states reduces pain and increases pain tolerance in
      laboratory studies. We tested whether completing positive activities in one's
      daily life produces long-term reductions in self-reported bodily pain in a
      randomized controlled trial of an online positive activities intervention.
      Participants recruited via the Web were randomly assigned to complete 0, 2, 4, or
      6 positive activities administered online over a 6-week period. Follow-up
      assessments were collected at the end of 6 weeks and at 1, 3, and 6 months
      postintervention. We used linear mixed effects models to examine whether the
      intervention reduced pain over time among those who had a score <67 on the bodily
      pain subscale of the Short Form-36 at baseline (N = 417; pain scores range from 0
      to 100; higher scores indicate less pain). Mean pain scores improved from
      baseline to 6 months in the 2-activity (55.7 to 67.4), 4-activity (54.2 to 71.0),
      and 6-activity (50.9 to 67.9) groups. Improvements were significantly greater (P
      < .05) in the 4-activity and 6-activity groups than in the 0-activity control
      group (54.1 to 62.2) in unadjusted and adjusted models. This study suggests that
      positive activities administered online can reduce bodily pain in adults with at
      least mild to moderate baseline pain. PERSPECTIVE: This study demonstrates that
      teaching people simple positive activities can decrease reported levels of bodily
      pain; moreover, these activities can be administered over the internet, a
      potential avenue for broadly disseminating health interventions at relatively low
      costs and with high sustainability.

PMID- 24568753
TI  - The realisation of a European health information system--time to get the
      politicians involved.

PMID- 24568754
TI  - Socioeconomic inequalities in the quality of life of older Europeans in different
      welfare regimes.
AB  - BACKGROUND: Whether socioeconomic inequalities in health and well-being persist
      into old age and are narrower in more generous welfare states is debated. We
      investigated the magnitude of socioeconomic inequality in the quality of life of
      Europeans in early old age and the influence of the welfare regime type on these
      relationships. METHODS: Data from individuals aged 50-75 years (n = 16 074)
      residing in 13 European countries were derived from Waves 2 and 3 of the Survey
      of Health, Ageing and Retirement in Europe. Slope indices of inequality (SIIs)
      were calculated for the association between socioeconomic position and CASP-12, a
      measure of positive quality of life. Multilevel linear regression was used to
      assess the overall relationship between socioeconomic position and quality of
      life, using interaction terms to investigate the influence of the type of welfare
      regime (Southern, Scandinavian, Post-communist or Bismarckian). RESULTS:
      Socioeconomic inequalities in quality of life were narrowest in the Scandinavian
      and Bismarckian regimes, and were largest by measures of current wealth. Compared
      with the Scandinavian welfare regime, where narrow inequalities in quality of
      life by education level were found in both men (SII = 0.02, 95% CI: -1.09 to
      1.13) and women (SII = 1.11, 95% CI: 0.05-2.17), the difference in quality of
      life between the least and most educated was particularly wide in Southern and
      Post-communist regimes. CONCLUSION: Individuals in more generous welfare regimes
      experienced higher levels of quality of life, as well as narrower socioeconomic
      inequalities in quality of life.

PMID- 24568755
TI  - Why does Spain have smaller inequalities in mortality? An exploration of
      potential explanations.
AB  - BACKGROUND: While educational inequalities in mortality are substantial in most
      European countries, they are relatively small in Spain. A better understanding of
      the causes of these smaller inequalities in Spain may help to develop policies to
      reduce inequalities in mortality elsewhere. The aim of the present study was
      therefore to identify the specific causes of death and determinants contributing
      to these smaller inequalities. METHODS: Data on mortality by education were
      obtained from longitudinal mortality studies in three Spanish populations
      (Barcelona, Madrid, the Basque Country), and six other Western European
      populations. Data on determinants by education were obtained from health
      interview surveys. RESULTS: The Spanish populations have considerably smaller
      absolute inequalities in mortality than other Western European populations. This
      is due mainly to smaller inequalities in mortality from cardiovascular disease
      (men) and cancer (women). Inequalities in mortality from most other causes are
      not smaller in Spain than elsewhere. Spain also has smaller inequalities in
      smoking and sedentary lifestyle and this is due to more smoking and physical
      inactivity in higher educated groups. CONCLUSION: Overall, the situation with
      regard to health inequalities does not appear to be more favourable in Spain than
      in other Western European populations. Smaller inequalities in mortality from
      cardiovascular disease and cancer in Spain are likely to be related to its later
      socio-economic modernization. Although these smaller inequalities in mortality
      seem to be a historical coincidence rather than the outcome of deliberate
      policies, the Spanish example does suggest that large inequalities in total
      mortality are not inevitable.

PMID- 24568756
TI  - Rothia mucilaginosa pneumonia in an immunocompetent patient.
AB  - Rothia mucilaginosa is a gram-postive coccus that occurs as part of the normal
      flora of the oropharynx and upper respiratory tract. Lower respiratory tract
      infections caused by this organism are rare and usually occur in
      immunocompromised patients. This is the case of an immunocompetent 47-year-old
      woman with right upper lobe pneumonia in which R.mucilaginosa was isolated in
      sputum and bronchial aspirate. Infections caused by this agent in the last four
      years in our hospital were reviewed. The most common predisposing factor was COPD
      with bronchiectasis. R.mucilaginosa was identified as the causative agent for
      pneumonia in only two cases, of which one was our case and the other was a
      patient with lung cancer. 

PMID- 24568758
TI  - [It lies in your hand!].

PMID- 24568757
TI  - Synthesis of 2-amino-3-cyano-4H-chromen-4-ylphosphonates and their anticancer
      properties.
AB  - A series of 2-amino-3-cyano-4H-chromen-4-ylphosphonates have been synthesized by
      reacting substituted salicylaldehydes, malononitrile, and dialkylphosphites using
      a catalytic amount of dibutylamine as an organocatalyst employing Knoevenagel,
      Pinner, and phospha-Michael reactions simultaneously in ethanol. This protocol is
      an environmentally friendly procedure and gives high yields of the desired
      compounds (85-96%). In addition, no extraction or chromatography steps are needed
      to obtain the desired products. The compounds are tested against the viability of
      adenocarcinomic human alveolar basal epithelial (A549) and human epidermoid
      cancer (KB) cell lines using an MTT assay. Among these, diethyl 2-amino-3-cyano
      4H-chromen-4-ylphosphonate and diethyl 2-amino-6-bromo-3-cyano-4H-chromen-4
      ylphosphonate showed promising anticancer activity against the two tested cell
      lines. 

PMID- 24568759
TI  - [Acute HIV infection].

PMID- 24568761
TI  - [Modern technologies in cranio-maxillofacial surgery].
AB  - Modern technologies are influencing medicine everyday. The oral and maxillofacial
      surgery meet the worlds from medicine and dentistry. So technologies from both
      fields are utilized. This article provides an overview about technologies in
      clinical use, which are typical for the specialty. Their principles and
      indications are described as well as benefits and limitations. Based on Cone Beam
      Computed Tomography image fusion and mirroring techniques are explained as well
      as patient specific models and implants, template guided and free surgical
      navigation with and without intraoperative three-dimensional imaging. An overall
      assessment reveals further need of research regarding indications and patient
      benefit. 

PMID- 24568762
TI  - [Raynaud's phenomenon and other circulatory disorders of the fingers].
AB  - Raynaud's phenomenon (RP) is defined as attacks of blanking, subsequent cyanosis
      and rubeosis of fingers due to vasospasms in response to cold or emotional
      stimuli. Primary RP has no known underlying cause and occurs mainly in young and
      otherwise healthy women. Secondary RP goes along with various causes such as
      connective tissue diseases, toxic substances, drugs, physical trauma or organic
      finger artery occlusions, and occurs at any age and in both genders. Related
      affections are acrocyanosis and finger artery occlusions either due to
      arteriosclerosis or vasculitis. Also spontaneous finger hematoma may provoke an
      episode of RP. Therapeutically strict cold protection and avoidance of possible
      noxa is recommended besides the treatment of underlying diseases. No standard
      vasoactive drug has proven ideal for RP due to side effects. In cases with rest
      pain or ulcerations the same principles are applied as in ischemic diseases with
      no possibility for revascularization.

PMID- 24568763
TI  - [Short time counseling in medical practice for improving health behaviour:
      problems and solutions].
AB  - Health related behaviour is a main determinant of chronic disease. Family
      physicians have an important role in the support of patients to improve their
      health behaviour, but relevant barriers should be addressed. In the new "Health
      Coaching KHM" program, patients and physicians are working as a team in four
      steps (sensitize - create motivation - plan - act). In this process, physicians'
      communication skills (which are trained within the program) are of utmost
      importance. In a pilot study with 20 family physicians and 1045 patients
      acceptance and feasibility were excellent: Every second participant improved her
      or his behaviour in the area of choice by at least one (of two possible)
      categories. For dissemination improving framework is crucial.

PMID- 24568765
TI  - [Intestinal malrotation in infants and young children].

PMID- 24568764
TI  - [Caplan's syndrome: rarely presenting as <<pulmorenal>> syndrome].
AB  - HISTORY AND ADMISSION FINDINGS: A 59-year-old man complained about having dry
      cough for months and a recent sudden onset of minor hemoptoe, asymmetric
      arthritis, myalgia as well as lack of appetite. He presented an occupational
      history of 12-year exposure to an organic dust as uranium miner in German
      Democratic Republic followed by 21 years as heavy construction worker in Germany
      and in Switzerland. Laboratory work-up tested positive for microhematuria and
      anti-neutrophilic cytoplasmic antibodies (ANCA). Chest X-rays and CT scan showed
      bilaterally scattered nodules. Thoracoscopic wedge resection was performed,
      histopathological analysis revealed granuloma with central necrotic area
      containing black coal dust and silica depositions surrounded by histiocytes. The
      pulmonary opacities on X-ray and the typical histology in the light of
      significant dust exposure allow the diagnosis of a Caplan's syndrome. TREATMENT
      AND COURSE: The symptoms improved rapidly under steroid therapy. Further
      investigations revealed a clear renal cell carcinoma as a cause for the
      persistent microhematuria. CONCLUSION: Rheumatoid arthritis, pulmonary nodules
      and history of prolonged dust exposure are classical findings that define
      Caplan's syndrome. These patients present with different immunological phenomena 
      in our case ANCA-positivity without vasculitis. Interestingly, the renal cell
      carcinoma which led to the "pulmorenal" syndrome in our patient is another health
      problem overrepresented in uranium mine workers.

PMID- 24568766
TI  - [Dual blockade of the renin-angiotensin system in diabetic patients is
      dangerous].

PMID- 24568767
TI  - [Blood pressure treatment is irrelevant immediately after ischemic stroke].

PMID- 24568769
TI  - [Syncope during smoking break].

PMID- 24568773
TI  - A herbal formula consisting of Rosae Multiflorae Fructus and Lonicerae Japonicae
      Flos inhibits inflammatory mediators in LPS-stimulated RAW 264.7 macrophages.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: A herbal formula (RL) consisting of Rosae
      Multiflorae Fructus (Yingshi) and Lonicerae Japonicae Flos (Jinyinhua) has been
      traditionally used to treat inflammatory disorders. This study aims to
      investigate the anti-inflammatory mode and mechanism of action of the ethanol
      extract of RL so as to provide a pharmacological basis for the use of RL in
      treating inflammatory diseases. MATERIALS AND METHOD: RL consisting of Yingshi
      and Jinyinhua (in 5:3 ratio) was extracted using absolute ethanol. We
      investigated its effects on nitric oxide (NO), interleukin-6 (IL-6), tumour
      necrosis factor (TNF)-alpha, inducible nitric oxide synthase (iNOS),
      cyclooxygenase-2 (COX-2), mitogen-activated protein kinases (MAPKs) and nuclear
      factor kappaB (NFkappaB) in mouse RAW 264.7 macrophages activated with
      lipopolysaccharide (LPS). RESULTS: RL could decrease the secretion of NO, IL-6
      and TNF-alpha into the culture medium and the cellular protein levels of iNOS and
      COX-2, which were associated with the reduction of the phosphorylation/activation
      of JNK and p38, and the inhibition of the transcriptional activity of NF-kappaB.
      CONCLUSIONS: The present study demonstrated an inhibitory effect of RL on the
      inflammatory mediators regulated by the NF-kappaB and MAPK signalling pathways in
      LPS-stimulated RAW 264.7 macrophages, providing a pharmacological basis for RL in
      the control of inflammatory disorders.

PMID- 24568772
TI  - Pulling out the 1%: whole-genome capture for the targeted enrichment of ancient
      DNA sequencing libraries.
AB  - Most ancient specimens contain very low levels of endogenous DNA, precluding the
      shotgun sequencing of many interesting samples because of cost. Ancient DNA
      (aDNA) libraries often contain <1% endogenous DNA, with the majority of
      sequencing capacity taken up by environmental DNA. Here we present a capture
      based method for enriching the endogenous component of aDNA sequencing libraries.
      By using biotinylated RNA baits transcribed from genomic DNA libraries, we are
      able to capture DNA fragments from across the human genome. We demonstrate this
      method on libraries created from four Iron Age and Bronze Age human teeth from
      Bulgaria, as well as bone samples from seven Peruvian mummies and a Bronze Age
      hair sample from Denmark. Prior to capture, shotgun sequencing of these libraries
      yielded an average of 1.2% of reads mapping to the human genome (including
      duplicates). After capture, this fraction increased substantially, with up to 59%
      of reads mapped to human and enrichment ranging from 6- to 159-fold. Furthermore,
      we maintained coverage of the majority of regions sequenced in the precapture
      library. Intersection with the 1000 Genomes Project reference panel yielded an
      average of 50,723 SNPs (range 3,062-147,243) for the postcapture libraries
      sequenced with 1 million reads, compared with 13,280 SNPs (range 217-73,266) for
      the precapture libraries, increasing resolution in population genetic analyses.
      Our whole-genome capture approach makes it less costly to sequence aDNA from
      specimens containing very low levels of endogenous DNA, enabling the analysis of
      larger numbers of samples. 

PMID- 24568774
TI  - Effects of Salvia miltiorrhiza on neural differentiation of induced pluripotent
      stem cells.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Salvia miltiorrhiza, a well-known traditional
      Chinese medicine, is commonly used to treat some neurological diseases because of
      its anti-oxidative, anti-inflammatory and anti-apoptotic properties. We
      investigate whether Salvia miltiorrhiza can improve the differentiation of
      induced pluripotent stem cells (iPSCs) into neurons in vitro, and promote iPSCs
      derived neural stem cells survival, integrate, and differentiation after their
      transplantation to the ischemic brain tissues. MATERIALS AND METHODS: Induced
      pluripotent stem cells were used to differentiate into neural stem cells, and
      further into neurons in induction medium with various concentrations of Salvia
      miltiorrhiza. The effects were assessed by immunofluorescence staining,
      quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and
      Western blotting. iPSC-derived neural stem cells were transplanted into the
      brains of rats with middle cerebral artery occlusion, immunofluorescence staining
      was used to evaluate survival, integrate, and differentiation of grafted cells,
      the functional recovery of the animals was tested by the Longa scores and
      spontaneous motor activity. RESULTS: Salvia miltiorrhiza (5MUg/ml) significantly
      increased the gene and protein expression of Nestin compared with that in other
      groups. Microtubule-associated protein 2 (MAP2) expression in induction medium
      with 5MUg/ml Salvia miltiorrhiza was significantly higher than that in the
      control group. After cells transplantation into the ischemic brain, more grafted
      MAP2(+) cells were found in Salvia miltiorrhiza-treated rats than others at 7
      days. Salvia miltiorrhiza-treated rats showed the most remarkable functional
      recovery at 7 and 14 days. CONCLUSION: Salvia miltiorrhiza induces
      differentiation of induced pluripotent stem cells to differentiate into neurons
      efficiently. The plant provides neuroprotection to implanted cells and improves
      functional recovery after their transplantation to the ischemic brain tissues.

PMID- 24568775
TI  - Tamoxifen induces resistance to activated protein C.
AB  - INTRODUCTION: The estrogen antagonist tamoxifen (TAM) increases the thrombotic
      risk similar to estrogen containing oral contraceptives (OC). In OC users this
      risk is attributed to alterations of hemostasis resulting in acquired resistance
      to activated protein C (APC). TAM-induced APC resistance has not been reported
      yet. MATERIALS AND METHODS: Blood samples were collected prospectively from women
      with breast cancer before (n=25) and monthly after start of adjuvant TAM
      treatment (n=75). APC resistance was evaluated on basis of the effect of APC on
      the endogenous thrombin generation potential. To detect increased in vivo APC
      generation APC plasma levels were measured using a highly sensitive
      oligonucleotide-based enzyme capture assay. Routine hemostasis parameters were
      measured additionally. RESULTS: APC sensitivity decreased by 41% (p=0.001)
      compared to baseline after one month of TAM application and remained
      significantly decreased during the study period. Free protein S increased
      (p=0.008) while other analyzed procoagulant factors, inhibitors, and activation
      markers of coagulation decreased or did not change significantly. In five
      patients the APC concentration increased to non-physiological levels but an
      overall significant increase of APC was not observed. CONCLUSIONS: This is the
      first study showing acquired APC resistance under TAM therapy. Acquired APC
      resistance might explain the increased thrombotic risk during TAM treatment.
      Observed changes of hemostasis parameters suggest different determinants of TAM
      induced APC resistance than in OC-induced APC resistance. The presence of
      acquired APC resistance in TAM patients warrants further evaluation if these
      patients may benefit from antithrombotic prophylaxis in the presence of
      additional thrombotic risk factors.

PMID- 24568776
TI  - Are direct oral anticoagulants such as edoxaban safer than heparin or vitamin K
      antagonists when intracranial hemorrhage occurs?

PMID- 24568778
TI  - Secrets--and lies? The seventh European Psychoanalytic Film Festival.

PMID- 24568777
TI  - Diagnosis and classification of rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is a systemic chronic inflammatory disease of unclear
      etiology that is manifested in by a progressive and destructive polyarthritis in
      association with serological evidence of autoreactivity. Its diagnosis is based
      on the classification criteria that involve four parameters: joint involvement,
      serology (rheumatoid factor and anti-cyclic citrullinated peptide--anti-CCP),
      levels of acute phase reactants and the duration of the symptoms Aletaha, et al.
      [1]. This classification simplifies the categorization of the patients with early
      RA; however, the diagnosis requires highly trained specialists who are able to
      differentiate early symptoms of RA from other pathologies.

PMID- 24568779
TI  - Selection of opponents in the prisoner's dilemma in dynamic networks: an
      experimental approach.
AB  - To investigate how a human subject selects her neighbors (opponents) to play the
      Prisoner's Dilemma within a social network, we conducted a human-subject
      experiment. The results are as follows: (1) A subject is more likely to dismiss
      the links to her neighbors most frequently when the subject chooses C and when
      the neighbor chooses D; (2) a subject who has more neighbors is less likely to
      dismiss links than a subject who has fewer neighbors; and (3) a subject is more
      likely to create links to (=select) opponents who have more neighbors than to
      opponents who have fewer neighbors. 

PMID- 24568780
TI  - Partial cross-enhancement in models for dengue epidemiology.
AB  - Four distinct serotypes of dengue virus co-circulate in many parts of the world.
      Antibodies to one serotype prevent infection with the homologous serotype, but
      may enhance infections with heterologous serotypes. Enhanced secondary infections
      have been implicated in the majority of severe cases, termed dengue hemorrhagic
      fever. Conventionally, mathematical models assume that all heterologous secondary
      infections are subject to enhanced susceptibility or transmissibility. However,
      empirical data show that only a minority of secondary infections lead to severe
      disease, which suggests that only a minority of secondary infections are subject
      to enhancement. We present a new modelling framework in which the population
      susceptible to secondary infection is split into a group prone to enhanced
      infection and a group with some degree of cross-protection. We use this framework
      to re-evaluate the role of enhanced infections in several well known dengue
      models that exhibit multi-annual epidemiological oscillations. We show that
      enhancement is unlikely to be driving such oscillations but may be modifying the
      effects of other drivers. 

PMID- 24568781
TI  - Support for vegetarians in decisions about animal products.

PMID- 24568782
TI  - Letter to the editor.

PMID- 24568783
TI  - High-volume image-guided injection for recalcitrant medial collateral ligament
      injuries of the knee.
AB  - AIM: To evaluate the effectiveness of a novel injection technique in the
      management of recalcitrant medial collateral ligament (MCL) injuries of the knee.
      MATERIALS AND METHODS: The injection, comprising 10 ml local anaesthetic with 25
      50 mg hydrocortisone, is directed beneath the periosteal attachment of the MCL.
      Twenty-eight patients who received the intervention were asked to complete a
      questionnaire, a visual analogue scale (VAS) and the International Knee
      Documentation Committee (IKDC) subjective knee form to quantify symptoms pre
      injection and at follow-up. Data were assessed using descriptive statistics.
      Further analysis was conducted using the Wilcoxon signed-rank test and Fisher's
      exact test. RESULTS: Sixty-eight percent (n = 19) of patients responded. Three
      patients were excluded according to the exclusion criteria. Of those studied,
      37.5% (n = 6) were professional athletes. At follow-up, patients reported a mean
      improvement on the VAS of 75.5% (SD = 23.6). There was a significant improvement
      in IKDC scores (mean difference 42%, SD = 14.2) pre- and post-injection (Wilcoxon
      signed-rank test, p < 0.001). No residual symptoms were reported by 50% (n = 8)
      of patients, and a further 37.5% (n = 6) of patients had improved. Of those
      patients who played sport, two-thirds (n = 10) had returned to their previous
      level of sport at follow-up, including all of the professional athletes.
      CONCLUSION: Periosteal high-volume image-guided injection is a useful treatment
      for recalcitrant MCL injury. Results are encouraging, particularly amongst the
      professional athletes studied.

PMID- 24568784
TI  - Development of KMnO(4)-releasing composites for in situ chemical oxidation of TCE
      contaminated groundwater.
AB  - The objective of this study was to develop a controlled-oxidant-release
      technology combining in situ chemical oxidation (ISCO) and permeable reactive
      barrier (PRB) concepts to remediate trichloroethene (TCE)-contaminated
      groundwater. In this study, a potassium permanganate (KMnO4)-releasing composite
      (PRC) was designed for KMnO4 release. The components of this PRC included
      polycaprolactone (PCL), KMnO4, and starch with a weight ratio of 1.14:2:0.96.
      Approximately 64% (w/w) of the KMnO4 was released from the PRC after 76 days of
      operation in a batch system. The results indicate that the released KMnO4 could
      oxidize TCE effectively. The results from a column study show that the KMnO4
      released from 200 g of PRC could effectively remediate 101 pore volumes (PV) of
      TCE-contaminated groundwater (initial TCE concentration = 0.5 mg/L) and achieve
      up to 95% TCE removal. The effectiveness of the PRC system was verified by the
      following characteristics of the effluents collected after the PRC columns
      (barrier): (1) decreased TCE concentrations, (2) increased ORP and pH values, and
      (3) increased MnO2 and KMnO4 concentrations. The results of environmental
      scanning electron microscope (ESEM) analysis show that the PCL and starch
      completely filled up the pore spaces of the PRC, creating a composite with low
      porosity. Secondary micro-scale capillary permeability causes the KMnO4 release,
      mainly through a reaction-diffusion mechanism. The PRC developed could be used as
      an ISCO-based passive barrier system for plume control, and it has the potential
      to become a cost-effective alternative for the remediation of chlorinated solvent
      contaminated groundwater. 

PMID- 24568785
TI  - Spectroscopic characterisation of dissolved organic matter changes in drinking
      water treatment: From PARAFAC analysis to online monitoring wavelengths.
AB  - Organic matter (OM) causes many problems in drinking water treatment. It is
      difficult to monitor OM concentrations and character during treatment processes
      due to its complexity. Fluorescence spectroscopy is a promising tool for online
      monitoring. In this study, a unique dataset of fluorescence excitation emission
      matrixes (EEMs) (n = 867) was collected from all treatment stages of five
      drinking water treatment plants (WTPs) situated in diverse locations from
      subtropical to temperate climate. The WTPs incorporated various water sources,
      treatment processes and OM removal efficiencies (DOC removal 0%-68%). Despite
      these differences, four common fluorescence PARAFAC components were identified
      for characterisation of OM concentration and treatability. Moreover, fluorescence
      component ratios showed site-specific statistically significant correlations with
      OM removal, which contrasted with correlations between specific UV absorbance at
      254 nm (SUVA) and OM removal that were not statistically significant. This
      indicates that use of fluorescence spectroscopy may be a more robust alternative
      for predicting DOC removal than UV spectroscopy. Based on the identified
      fluorescence components, four optical locations were selected in order to move
      towards single wavelength online OM monitoring. 

PMID- 24568786
TI  - Disinfection of water by adsorption combined with electrochemical treatment.
AB  - The disinfection performance of a unique process of adsorption combined with
      electrochemical treatment is evaluated. A flake graphite intercalation compound
      adsorbent was used, which is effective for the removal of organic contaminants
      and is amenable to anodic electrochemical regeneration. Adsorption of Escherichia
      coli on the graphite flake was followed by electrochemical treatment under a
      range of experimental conditions in a sequential batch reactor. The adsorption of
      E. coli cells was found to be a fast process and was capable of removing >99.98%
      of cells from solution after 5 min with a ca. 6.5-log10 reduction in E. coli
      concentration after 10 min. With electrochemical treatment the adsorbent could be
      reused, with no decrease in E. coli adsorption observed over five cycles. In the
      presence of chloride, >8.5-log10 reduction of E. coli concentration was achieved.
      Disinfection was found to be less effective in the absence of chloride. However,
      selection of appropriate operating conditions enabled effective disinfection in a
      chloride free system, reducing the potential for formation of disinfection by
      products. The energy consumption required to achieve >8.5-log10 disinfection was
      2-7 kWh m(-3). 

PMID- 24568787
TI  - Enhancing disinfection by advanced oxidation under UV irradiation in
      polyphosphate-containing wastewater flocs.
AB  - In this paper, the role of naturally occurring polyphosphate in enhancing the
      ultraviolet disinfection of wastewater flocs is examined. It was found that
      polyphosphate, which accumulates naturally within the wastewater flocs in the
      enhanced biological phosphorus removal process, is capable of producing hydroxyl
      radicals under UV irradiation and hence causing the photoreactive disinfection of
      microorganisms embedded within flocs. This phenomenon is likely responsible for
      the improved UV disinfection of the biological nutrient removal (BNR) effluent
      compared to that of conventional activated sludge effluent by as much as 1 log. A
      mathematical model is developed that combines the chemical disinfection by
      hydroxyl radical formation within flocs, together with the direct inactivation of
      microorganisms by UV irradiation. The proposed model is able to quantitatively
      explain the observed improvement in the UV disinfection of the BNR effluents.
      This study shows that the chemical composition of wastewater flocs could have a
      significant positive impact on their UV disinfection by inducing the production
      of oxidative species. 

PMID- 24568788
TI  - Nitrogen availability increases the toxin quota of a harmful cyanobacterium,
      Microcystis aeruginosa.
AB  - An important objective in understanding harmful phytoplankton blooms is
      determining how environmental factors influence the toxicity of bloom-forming
      species. We examined how nutrients and grazers (dreissenid mussels) affect the
      production of microcystin (a liver toxin) by the cyanobacterium Microcystis
      aeruginosa, via a combination of field and laboratory experiments, and field
      observations in Lake Erie. The field experiment revealed no effect of mussel
      density on microcystin quota (particulate microcystin per unit Microcystis
      biomass). In contrast, in both field and laboratory experiments, nitrogen-limited
      conditions led to substantially reduced microcystin quota relative to phosphorus
      limited or nutrient-saturated conditions. In the field experiment, microcystin
      per unit of mcyB gene was strongly reduced under nitrogen-limited conditions,
      indicating a phenotypic response. Results from a seasonal survey in the western
      basin of Lake Erie revealed a similar negative influence of nitrogen limitation
      (as indexed by nitrate concentration) on microcystin quota. Our results are
      consistent with stoichiometric considerations in that the cell quota of a
      nitrogen-rich secondary metabolite, microcystin, was reduced disproportionately
      under nitrogen limitation. 

PMID- 24568789
TI  - Performance of ceramic ultrafiltration membranes and fouling behavior of a dye
      polysaccharide binary system.
AB  - Ultrafiltration membrane processes have become an established technology in the
      treatment and reuse of secondary effluents. Nevertheless, membrane fouling arises
      as a major obstacle in the efficient operation of these systems. In the current
      study, the performance of tubular ultrafiltration ceramic membranes was evaluated
      according to the roles exerted by membrane pore size, transmembrane pressure and
      feed concentration on a binary foulant system simulating textile wastewater. For
      that purpose, carboxymethyl cellulose sodium salt (CMC) and an azo dye were used
      as colloidal and organic foulants, respectively. Results showed that a larger
      pore size enabled more solutes to get adsorbed into the pores, producing a sharp
      permeate flux decline attributed to the rapid pore blockage. Besides, an increase
      in CMC concentration enhanced severe fouling in the case of the tighter membrane.
      Concerning separation efficiency, organic matter was almost completely removed
      with removal efficiency above 98.5%. Regarding the dye, 93% of rejection was
      achieved. Comparable removal efficiencies were attributed to the dynamic membrane
      formed by the cake layer, which governed process performance in terms of
      rejection and selectivity. As a result, none of the evaluated parameters showed
      significant influence on separation efficiency, supporting the significant role
      of cake layer on filtration process. 

PMID- 24568790
TI  - Micro-Raman, mid-IR, far-IR and DFT studies on 2-[4-(4
      fluorobenzamido)phenyl]benzothiazole.
AB  - Molecular structure of 2-[4-(4-Fluorobenzamido)phenyl]benzothiazole was
      determined by quantum chemical calculations. MidIR and FarIR spectra were
      recorded at room temperature, with 4 cm(-1) resolution in the 4000-400 cm(-1) and
      700-30 cm(-1) regions, respectively for the first time. Raman spectrum was
      recorded in the 4000-100 cm(-1) range. Optimized molecular structure and
      vibrational wavenumbers of the compound in its ground state have been calculated
      by using Density Functional Theory using B3LYP functional with 6-311++G(d,p)
      basis set. Vibrational wavenumbers were seen to be in good agreement with the
      experimental IR data. Furthermore, assignments of each vibrational mode were
      interpreted in terms of potential energy distributions in detail.

PMID- 24568791
TI  - Solvatochromic behavior of some alpha-styrylpyridinium dyes.
AB  - The influences of solvent polarity and substituent on the electronic transition
      of six different N-butyl-alpha-styrylpyridinium dyes have been investigated in 21
      solvents. Reichardt's E(T)(30) scale has been used to propose a quantitative
      approach towards the relative stability of the electronic ground and excited
      state species. The solvents have been classified into three types and the dyes
      have been classified into four groups based on the contribution of field and
      inductive effects of the substituents towards the change in their absorption
      maxima values. Instead of a steady solvatochromism, all the dyes except p-nitro
      substituted one, suffer reversals in solvatochromism at E(T)(30) values of ~37
      and ~48. The extents of contribution of non-polar and polar protic solvents
      towards the solvation of the excited states of the dye molecules have been
      determined to be 30-40% more than that towards the stability of their ground
      states by the dipolar aprotic solvents. The ortho effect shown by this class of
      dyes in contrast to their corresponding gamma-isomers might have been responsible
      for their better solvent polarity sensing capability.

PMID- 24568792
TI  - Tools for determining critical levels of atmospheric ammonia under the influence
      of multiple disturbances.
AB  - Critical levels (CLEs) of atmospheric ammonia based on biodiversity changes have
      been mostly calculated using small-scale single-source approaches, to avoid
      interference by other factors, which also influence biodiversity. Thus, it is
      questionable whether these CLEs are valid at larger spatial scales, in a multi-
      disturbances context. To test so, we sampled lichen diversity and ammonia at 80
      sites across a region with a complex land-cover including industrial and urban
      areas. At a regional scale, confounding factors such as industrial pollutants
      prevailed, masking the CLEs. We propose and use a new tool to calculate CLEs by
      stratifying ammonia concentrations into classes, and focusing on the highest
      diversity values. Based on the significant correlations between ammonia and
      biodiversity, we found the CLE of ammonia for Mediterranean evergreen woodlands
      to be 0.69 MUg m(-3), below the previously accepted value of 1.9 MUg m(-3), and
      below the currently accepted pan-European CLE of 1.0 MUg m(-3). 

PMID- 24568793
TI  - Mercury distribution in the foliage and soil profiles of the Tibetan forest:
      processes and implications for regional cycling.
AB  - Remote forests are considered a pool of Mercury (Hg) in the global Hg cycle.
      However, notably few studies have investigated the fate of Hg in the Tibetan
      forest. In this study, fifty-two foliage samples and seven litter/soil profiles
      were collected throughout the Tibetan forest. The concentrations of total Hg
      (THg) in foliage were positively correlated with longitude and negatively
      correlated with altitude, indicating that the emission of Hg is expected to
      decrease with increasing distance from emission sources to the Tibetan forest.
      The deposition flux of THg in the Tibetan forest (with an air-to-forest ground
      flux of 9.2 MUg/m(2)/year) is ~2 times the flux in clearings, which is suggestive
      of enhanced Hg deposition by the forest. The depositional Hg is eventually stored
      in the forest soil, and the soil acts as a net 'sink' for Hg. 

PMID- 24568794
TI  - Management of traumatic labral tear in acetabular fractures with posterior wall
      component.
AB  - BACKGROUND: Posterior labral tear is frequently encountered in acetabular
      fractures with posterior wall component (AFPWC). However, there has been very
      little information in the literature on the type and management of traumatic
      labral tears in AFPWC. HYPOTHESIS: Traumatic labral tear is a constant
      intracapsular injury in AFPWC and can be repaired using adequate methods
      according to its type and size. MATERIALS AND METHODS: A retrospective study of
      14 patients (mean age 38 years [16-58]) who underwent open surgery for AFPWC was
      conducted using prospectively collected data. The types of posterior labral tear
      were investigated at intraoperative examination through the ruptured joint
      capsule or its extension, and were concomitantly managed. Surgical outcomes were
      clinically assessed using Merle d'Aubigne (PMA) score and Visual Analog Scale
      (VAS), and radiologically evaluated at final follow-up. RESULTS: Posterior labral
      tears were present in all 14 patients. The types of labral tear were osseous
      avulsion and posterior root avulsion tear (n=9), longitudinal peripheral tear and
      posterior root avulsion tear (n=2), longitudinal peripheral tear (n=2), and
      osseous avulsion tear (n=1). All unstable labra in 12 patients (86%) were
      repaired. All avulsion tears of the posterior root were repaired using a suture
      anchor, longitudinal peripheral tears using suture fixation or/and suture
      anchors, and osseous avulsion tears using a spring plate. The mean PMA score and
      VAS were 16.4 (14-18) and 1.7 (0-3) at final follow-up, respectively. The
      radiologic grades at last follow-up were good or excellent in all patients.
      DISCUSSION: All AFPWC in this study consistently revealed posterior labral tear.
      Posterior root avulsion tears accompanied with osseous avulsion was the most
      common type. Torn labra should be repaired as much as possible if unstable,
      considering the important functions of a normal labrum; fixation using a suture
      anchor may be useful for an avulsion tear of the posterior root. LEVEL OF
      EVIDENCE: Level IV, therapeutic case series.

PMID- 24568795
TI  - Reference interval evaluation of high-sensitivity troponin T and N-terminal B
      type natriuretic peptide in Vietnam and the US: The North South East West Trial.
AB  - BACKGROUND: Reference intervals of high-sensitivity troponin T (hs-cTnT) and N
      terminal pro-B-type natriuretic peptide (NT-proBNP) have been determined from
      Western populations. No data are available regarding expected values in Asian
      populations. METHODS: A total of 1157 age- and sex-matched healthy individuals
      (mean age, 41.2 years; 48.0% male) were prospectively enrolled from the US (n =
      565) and Vietnam (n = 592). Blood samples were analyzed for hs-cTnT and NT
      proBNP. Median values were determined for each country and compared in unadjusted
      analyses and in analyses adjusted for age, sex, body mass index, study site,
      race, and vital signs. RESULTS: Median hs-cTnT concentrations were slightly
      higher for individuals from the US than for those from Vietnam, but both were
      below the limit of detection (3.7 vs 3.0 ng/L, respectively; P = 0.03). More US
      participants had an hs-cTnT concentration above the limit of detection (57.2% vs
      47.3%; P = 0.001), but the 99th percentile concentration was slightly higher for
      Asians (US 15.1 vs Vietnam 19.0 ng/L). Concentrations for >98% of both
      populations were below the standard hs-cTnT 99th percentile of 14.0 ng/L (P =
      0.54). Median NT-proBNP concentrations were slightly higher for US participants
      compared with Vietnamese participants (28 vs 16 ng/L, respectively; P < 0.001).
      Following adjustment, differences in concentrations of NT-proBNP between healthy
      US and Vietnamese populations remained significant, whereas for hs-cTnT the
      differences were no longer significant. Inclusion of hs-cTnT values down to the
      limit of blank did not change the result. CONCLUSIONS: The differences in hs-cTnT
      and NT-proBNP between healthy individuals from the US and Vietnam are small.
      Previously derived reference intervals for both analytes may be applied in Asian
      populations.

PMID- 24568796
TI  - Two-dimensional gel electrophoresis and the beginning of proteomics.

PMID- 24568798
TI  - The effect of an eyes-closed dance-specific training program on dynamic balance
      in elite pre-professional ballet dancers: a randomized controlled pilot study.
AB  - Visual conditions for a dancer vary greatly between theatrical performance
      environments and dance studios, and this variability may be detrimental to their
      dynamic balance performance, particularly under stage lighting. In order to
      maintain balance control, dancers reportedly rely heavily on visual input, yet
      those who rely more on proprioceptive strategies for balancing have been found to
      be more stable. The purpose of this study was to assess the capability of an eyes
      closed, dance-specific training program to nurture in dancers proprioceptive
      mechanisms that may facilitate their dynamic balance control. Eighteen elite pre
      professional ballet dancers were randomly assigned to either a control (eyes
      open) or experimental (eyes closed) group for the intervention. The balance
      abilities of all subjects were tested using five dance-specific variations of the
      Star Excursion Balance Test before and after a 4 week balance intervention. Reach
      distance and time to complete the tests were recorded separately as indirect
      measurements of dynamic balance. The intervention consisted of dance-specific,
      eyes-closed exercises integrated into the dancers' daily ballet class and
      designed progressively to challenge the dancers' balance. During the intervention
      period, the control group undertook the same exercise program with their eyes
      open. Results revealed significant improvements in time to complete the three
      "timed" balance tests, and distances reached significantly improved in one of the
      two "reach" balance tests. No significant improvements were observed in the
      control group for any variation of the tests. These results indicate that dancers
      can be trained to adopt proprioceptive strategies to maintain dynamic balance,
      which consequently improves their balance performance. Such findings could
      encourage use of eyes-closed training in daily dance classes due to its potential
      to improve dancers' balance control. 

PMID- 24568799
TI  - An accelerated step test to assess dancer pre-season aerobic fitness.
AB  - As the technical performance demands of dance increase, professional companies
      and pre-professional schools are implementing pre-season screenings that require
      an efficient, cost effective way to measure dancer aerobic fitness. The aim of
      this study was to assess an accelerated 3-minute step test (112 beats.min(-1)) by
      comparing it to the well-studied YMCA step test (96 beats.min(-1)) and a
      benchmark standard, an incremental treadmill test, using heart rate (HR) and
      oxygen consumption (VO2) as variables. Twenty-six professional and pre-
      professional dancers (age 20 +/- 2.02 years) were fitted with a telemetric gas
      analysis system and HR monitor. They were tested in the following order: 96 step,
      112 step, and treadmill test, with rest to return to baseline heart rate between
      each test. The step and treadmill tests were compared using Intra-class
      Correlation Coefficients [ICC (3, k)] calculated with analysis of variance (p <
      0.05). To determine whether there was a relationship between peak and recovery HR
      (HRpeak, HRrecov) and VO2(VO2peak, VO2recov) variables, Pearson product moment
      correlations were used. Differences due to gender or group (pre- professionals
      versus professionals) were explored with MANOVAs for HRpeak, VO2peak, HRrecov,
      VO2recov, and fitness category. The 112 step test produced higher HRpeak and
      VO2peak values than the 96 step test, reflecting a greater workload (p < 0.001).
      For HRpeak, there were high correlations (r = 0.71) and for HRrecov, moderate
      correlations (r = 0.60) between the 112 step test and treadmill test. For VO2peak
      and VO2recov, there were moderate correlations between the 112 step test and
      treadmill test (r = 0.65 and 0.73). No differences between genders for VO2peak
      values were found for either step test, but males displayed lower HRpeak values
      for both step tests and higher VO2peak values during the treadmill test (p <
      0.001). Recovery HR was lower in males for the 96 and 112 step tests (p < 0.05).
      This was reflected in higher fitness scores. There were no differences between
      groups in any of the variables when only females were compared. For the 112 step
      test, correlations between HRpeak and HRrecov were high (r = 0.85), and
      correlations between HRpeak and fitness category were very high (r = 0.98). It is
      concluded that the 112 step test provides an efficient, acceptable tool for
      testing dance populations, though further testing in larger groups of dancers
      representing a diverse range of genres and training levels is needed. 

PMID- 24568800
TI  - Traumatic injuries in revue dancers.
AB  - Revue productions are a combination of dancing and singing, musical and spoken
      sequences, and acrobatics, performed with or without a story line, and
      characterized by a versatility of dance styles and a high number of performances
      (over 250 in a 10-month season). The aim of this quantitative single cohort study
      is to evaluate work-related traumatic injuries in this dance genre. Data were
      obtained from work accident reports of the German Social Accident Insurance
      Institution for the public sector in Berlin (UKB) involving 440 revue dancers
      (183 males and 257 females). Analysis was conducted with Excel 2007 and PASW
      Statistics 18. One out of three female dancers and one out of two male dancers
      sustained an acute injury in the course of a theatrical season (0.22 injuries per
      1,000 hours). The incidence rate was 0.44 for males and 0.31 for females, with
      the lower extremity as the most commonly injured body region, followed by the
      spine. Of all occupational accidents, 75.1% happened on stage, with 69% during
      performances. The dance partner and dance floor were the most common exogenous
      factors resulting in a traumatic injury. Of all traumatic injuries, 81.7%
      occurred in the first 3 hours after starting work. Gender specific differences
      could be observed. Due to the limited availability of comparable studies of other
      forms of professional dance, in this study revue dance is largely considered as
      an independent genre. 

PMID- 24568797
TI  - Dietary intake, nutrition, and fetal alcohol spectrum disorders in the Western
      Cape Province of South Africa.
AB  - In this study, we describe the nutritional status of women from a South African
      community with very high rates of fetal alcohol spectrum disorders (FASD).
      Nutrient intake (24-h recall) of mothers of children with FASD was compared to
      mothers of normal controls. Nutrient adequacy was assessed using Dietary
      Reference Intakes (DRIs). More than 50% of all mothers were below the Estimated
      Average Requirement (EAR) for vitamins A, D, E, and C, thiamin, riboflavin,
      vitamin B6, folate, calcium, magnesium, iron, and zinc. Mean intakes were below
      the Adequate Intake (AI) for vitamin K, potassium, and choline. Mothers of
      children with FASD reported significantly lower intake of calcium,
      docosapentaenoic acid (DPA), riboflavin, and choline than controls. Lower intake
      of multiple key nutrients correlates significantly with heavy drinking. Poor diet
      quality and multiple nutritional inadequacies coupled with prenatal alcohol
      exposure may increase the risk for FASD in this population. 

PMID- 24568802
TI  - The relationship between passion and the psychological well-being of professional
      dancers.
AB  - The Dualistic Model of Passion defines passion as an intense desire or enthusiasm
      for a self-defining activity that people love, consider important, and devote
      significant amounts of time and energy to. The model proposes two distinct types
      of passion, harmonious (HP) and obsessive (OP). HP occurs when the activity is
      autonomously internalized into the individual's life and identity, while OP is a
      result of a controlled internalization of the activity. The aim of this study was
      to investigate the prevalence and type of passion professional dancers have for
      dance in relation to their psychological well-being, specifically eating
      attitudes, self-esteem, and perfectionism. Participants were 92 professional
      dancers, aged 19 to 35 years (M = 27.03, SD = 3.84), and mostly from the United
      States, the United Kingdom, and Canada. Results revealed that HP positively
      predicted self-esteem (SE), while OP positively predicted self-evaluative
      perfectionism (SEP), conscientious perfectionism (CP), and disordered eating
      attitudes (EAT-26). Additionally, SEP was found to mediate the relationship
      between OP and EAT-26, suggesting that OP may lead to SEP, which could in turn
      motivate disordered eating. Overall, the results of this study have supported and
      extended previous research suggesting that the two types of passion can have
      divergent effects on aspects of psychological well-being. Findings indicate that
      HP should be encouraged and OP discouraged among dancers, for example, via
      autonomy supportive behaviors of teachers. 

PMID- 24568801
TI  - Combined triaxial accelerometry and heart rate telemetry for the physiological
      characterization of Latin dance in non-professional adults.
AB  - The purpose of this study was to value calibrate, cross-validate, and determine
      the reliability of a combined triaxial accelerometry and heart rate telemetry
      technique for characterizing the physiological and physical activity parameters
      of Latin dance. Twenty-two non-professional adult Latin dancers attended two
      laboratory-based dance trials each. After familiarization and a standardized warm
      up, a multi-stage (3 x 5-minute) incremental (based on song tempo) Afro-Cuban
      salsa choreography was performed while following a video displayed on a
      projection screen. Data were collected with a portable indirect calorimeter, a
      heart rate telemeter, and wrist-, hip-, and ankle-mounted ActiGraph GT3X+
      accelerometers. Prediction equations for energy expenditure and step count were
      value calibrated using forced entry multiple regression and cross-validated using
      a delete-one jackknife approach with additional Bland-Altman analysis. The
      average dance intensity reached 6.09 +/- 0.96 kcal/kg/h and demanded 45.9 +/-
      11.3% of the heart rate reserve. Predictive ability of the derived models was
      satisfactory, where R(2) = 0.80; SEE = 0.44 kcal/kg/h and R(2) = 0.74; SEE = 3
      step/min for energy expenditure and step count, respectively. Dependent t-tests
      indicated no differences between predicted and measured values for both energy
      expenditure (t65 = -0.25, p = 0.80) and step count (t65 = -0.89, p = 0.38). The
      95% limits of agreement for energy expenditure and step count were -0.98 to 0.95
      kcal/kg/h and -7 to 7 step/min, respectively. Latin dance to salsa music elicits
      physiological responses representative of moderate to vigorous physical activity,
      and a wrist-worn accelerometer with simultaneous heart rate measurement
      constitutes a valid and reliable technique for the prediction of energy
      expenditure and step count during Latin dance. 

PMID- 24568803
TI  - [Leave traces].

PMID- 24568804
TI  - Attitudes of Swiss veterinarians towards pain and analgesia in dogs and cats.
AB  - A survey was performed to evaluate the use of perioperative analgesia in dogs and
      cats by veterinary practitioners. Questions were grouped in seven sections
      recording personal data, education in veterinary analgesia, general ideology
      regarding treatment of perioperative pain, personal experience, assessment, and
      use of main analgesics to treat perioperative pain. A total of 258 received forms
      were analyzed. Based on 5 questions, 88 % showed excellent motivation to use
      perioperative pain therapy. The main reason declared for the use of analgesics
      was to relieve the patient from pain (64.1 %). Most veterinarians reported to
      routinely administer analgesics before (71 - 96 %) or after (2 - 23 %) surgery.
      The most used analgesics were non-steroidal anti-inflammatory drugs (carprofen,
      meloxicam) and opioids (butorphanol, buprenorphine). Animals were routinely
      evaluated for pain after recovery. Only 43.8 % of veterinarians declared to use
      loco-regional anaesthesia. Swiss veterinarians appear to recognize well the need
      for perioperative pain treatment. However, weakness was shown in evaluating pain
      severity, distinguishing between opioid classes, and using loco-regional
      anaesthesia. 

PMID- 24568805
TI  - Comparative investigations on the upper respiratory tract in Norwich terriers,
      brachycephalic and mesaticephalic dogs.
AB  - For some time Norwich terriers have been known to suffer from respiratory
      problems. In order to assign this weakness to a pathophysiology, 23 terriers were
      examined clinically, with laryngoscope and with rhinomanometry. In addition their
      skulls were dimensioned on radiographs. Widened nostrils, overlong soft palates
      and the everted laryngeal pouches were consistent with brachycephalic syndrome.
      Resistance values in the nasal passage corresponded to the appearance in
      brachycephalic dogs. Skull measurements gave inconsistent results, because length
      to width ratios and craniofacial angles denoted mesaticephaly, whereas the facial
      to cranial length ratios (S-index = 0.65) lay in the brachycephalic sector. It
      can be concluded, that the Norwich terrier breed is in transition towards
      brachycephaly with some individual dogs already suffering from the brachycephalic
      syndrome. Breeders are requested to introduce necessary counter measures. 

PMID- 24568806
TI  - [Lens luxation in dogs: a retrospective study of 134 dogs (2000-2011)].
AB  - This retrospective study evaluated cases of lens luxation in dogs that were
      documented at the University of Zurich Veterinary Teaching Hospital between 2000
      and 2011. A total 134 dogs were included in the study. This population of dogs
      with lens luxation represents 0.41 % of all dogs presented to the Zurich
      Veterinary Teaching Hospital (32'523) and 3.02 % of all dogs presented to the
      ophthalmology service during the same time period. The 134 dogs represented over
      40 different breeds, including mixed breeds. 63 of the dogs were male, 71 were
      female. The 134 dogs were divided in primary lens luxation (86 of the 134 dogs,
      64 %) and secondary lens luxation (48 dogs, 36 %). The most frequent causes for
      secondary lens luxation were glaucoma (58 %), cataract (19 %) and trauma (17 %).
      This study shows the predisposition for primary lens luxations in terrier breeds,
      Chinese Crested dogs, Pinscher and Spitz. In contrast, Siberian Huskies, Basset
      Hounds, Bearded Collies, Cairn Terriers, mixed breed dogs, Bolonka Zwetna, Boston
      Terriers, Borzoi, Doberman, Eurasian, Leonberg, Luzerner Niederlaufhund and
      Weimaraner suffered significantly more often from secondary lens luxation. There
      was no sex predilection for primary or secondary lens luxation. Dogs with primary
      lens luxation were on average 7.39 +/- 3.02 years old, which is significantly
      younger than the dogs with secondary lens luxation (9.12 +/- 3.38 years). Dogs
      with primary lens luxation showed a significantly higher rate of a bilateral
      development than those with secondary lens luxation (85.5 % of the dogs with
      primary lens luxation and only 14.5 % of the dogs with secondary lens luxation
      showed it in both their eyes). 

PMID- 24568807
TI  - Tachycardia-induced cardiomyopathy in a cat.
AB  - A 10-year-old male castrated Domestic Shorthair cat was evaluated for an
      asymptomatic tachyarrhythmia noted two weeks prior. Electrocardiography revealed
      a normal sinus rhythm with atrial premature complexes and paroxysms of
      supraventricular tachycardia with a heart rate between 300 and 400 min-1.
      Echocardiography was unremarkable, and concentrations of circulating cardiac
      troponin I, T4, and blood taurine were within reference ranges. The cat was
      treated with sotalol (2.1 mg/kg q12h, PO) but the arrhythmia was insufficiently
      controlled as determined during several re-examinations within a two-year time
      period. Twenty four months after initial presentation atrial fibrillation with
      fast ventricular response rate (200 to 300 min-1) was diagnosed, along with
      severe eccentric chamber remodeling and systolic dysfunction. The cat developed
      congestive heart failure and cardiogenic shock and was euthanized nearly 27
      months after the first exam. Gross and histopathologic findings ruled out
      commonly seen types of primary myocardial disease in cats. The persistent nature
      of the tachyarrhythmia, the progressive structural and functional cardiac
      changes, and comparative gross and histopathologic post-mortem findings are
      consistent with the diagnosis of tachycardia-induced cardiomyopathy. 

PMID- 24568815
TI  - Regenerative bladder augmentation using autologous tissue-when will we get there?

PMID- 24568816
TI  - Comparative outcomes in the management of the renal mass.

PMID- 24568818
TI  - Sudden cardiac death. Introduction to the special supplement.

PMID- 24568820
TI  - Cost-effectiveness of implantable cardioverter-defibrillator in today's world.
AB  - The implantable cardioverter-defibrillator (ICD) is an example of an effective
      intervention with high up-front costs and delayed benefits. It has become a
      proven and well-accepted therapy not only for secondary but also for primary
      prevention of sudden cardiac death in patients with ischemic and non-ischemic
      heart disease. In recent years, the international guidelines have extended the
      indications to the prophylactic ICD, increasing the number of eligible patients
      and, together, the financial challenges of a widespread implementation. In this
      article, we review the available economic tools that can help address the ICD
      cost issue. We think that the awareness of such knowledge may facilitate
      dialogues between physicians, administrators and policy-makers, and help foster
      rational decision making. 

PMID- 24568821
TI  - Post-resuscitation care for survivors of cardiac arrest.
AB  - Cardiac arrest can occur following a myriad of clinical conditions. With
      advancement of medical science and improvements in Emergency Medical Services
      systems, the rate of return of spontaneous circulation for patients who suffer an
      out-of-hospital cardiac arrest (OHCA) continues to increase. Managing these
      patients is challenging and requires a structured approach including
      stabilization of cardiopulmonary status, early consideration of neuroprotective
      strategies, identifying and managing the etiology of arrest and initiating
      treatment to prevent recurrence. This requires a closely coordinated
      multidisciplinary team effort. In this article, we will review the initial
      management of survivors of OHCA, highlighting advances and ongoing controversies.

PMID- 24568819
TI  - Mechanisms of sudden cardiac death.
AB  - Worldwide, sudden cardiac death (SCD) is a major problem. It is most frequently
      caused by ventricular tachyarrhythmias: Monomorphic and polymorphic ventricular
      tachycardia (VT), torsade de pointes (TdP), and ventricular fibrillation (VF).
      Beta blockade, ACE inhibition, coronary reperfusion and other treatments have
      reduced the incidence of VT but pulseless electrical activity (PEA) is
      increasingly seen, particularly in patients with advanced chronic heart disease.
      From existing data, bradyarrhythmia in the form of asystole (usually complete
      heart block without escape rhythm) causes only a minor proportion (10-15%) of
      SCD. In patients aged 50 years and more, coronary artery disease plays a dominant
      role causing more than 75% of SCD cases, either by acute ischemia and ventricular
      fibrillation or by chronic scar formation and reentrant VT. In younger patients,
      SCD may occur in patients with structurally normal hearts. A number of
      arrhythmogenic disorders with an increased risk of SCD have been detected and
      better understood recently, such as long and short QT syndrome, Brugada syndrome,
      catecholaminergic polymorphic ventricular tachycardia, and the early
      repolarization syndrome. Most importantly, ECG signs and clinical features
      indicating high risk for SCD have been identified. Knowledge of the exact
      electrophysiologic mechanisms of ventricular tachyarrhythmias at the cellular
      level has been improved and mechanisms such as phase 2 reentry and reflection
      proposed to better understand why and how SCD occurs. 

PMID- 24568822
TI  - Pharmacotherapy to reduce arrhythmic mortality.
AB  - Fatal ventricular arrhythmias and heart failure are the common modes of death in
      patients with cardiovascular diseases. Intracardiac defibrillator (ICD)
      implantation reduces arrhythmic mortality to a significant extent in the high
      risk patient. However, there continues to be a need for effective drug therapy to
      reduce the arrhythmic and overall mortality in patients with or without an ICD.
      Although anti-arrhythmic drugs (AAD) appear inferior to ICD, the role of beta
      blockers and to an extent amiodarone along with non AAD like angiotensin
      converting enzyme inhibitors (ACE-I), mineralocorticoid blockers (MRB) and HMG
      CoA reductase inhibitors (statins) need to be emphasized. There have been many
      drug trials and meta-analysis to this effect and we review the role of drugs
      especially in their ability to reduce arrhythmic mortality and sudden cardiac
      death (SCD). The focus is on post myocardial infarction (MI) and heart failure
      patients with a brief overview of role of drugs in channelopathies. 

PMID- 24568824
TI  - Global burden of Sudden Cardiac Death and insights from India.
AB  - Sudden Cardiac death (SCD) is a major clinical event causing adverse impact on
      global economy. This review summarizes the available epidemiological data on SCD
      from different parts of the world. It contrasts the Indian and global perception
      on the issues influencing data collection, burden of SCD and sudden deaths
      occurring following Myocardial Infarction. The differences in data from India and
      rest of the world are highlighted. 

PMID- 24568823
TI  - Prevention of sudden cardiac death beyond the ICD: have we reached the boundary
      or are we just burning the surface?
AB  - Preventing sudden cardiac death (SCD) remains a major unsolved problem in
      contemporary medical practice. As the most common cause of SCD, treatment for
      ventricular arrhythmias is the target area of interest in research field. While
      implantable cardioverter-defibrillator (ICD) effectively decreases death from
      ventricular arrhythmias in highly selected patients, risk of inappropriate
      shocks, mortality from frequent therapy, chance of failing in abortion of
      arrhythmias despite having a defibrillator, and our inability to recognize which
      of several hundreds of thousands of patients at risk for sudden death but do not
      meet current criteria for defibrillator, limit ICD effectiveness. In this
      article, a brief review of mechanism leading to SCD, the existing evidence for a
      defibrillator and the lacunae in present guidelines for patients clearly at risk
      for sudden death but without proven benefit from a defibrillator are presented in
      Section I. Following this, interventional approaches, both catheter-based and
      general measures that may serve as adjuncts to a defibrillator in preventing this
      all too common catastrophic end event, are summarized in Section II. 

PMID- 24568825
TI  - Sudden cardiac arrest.

PMID- 24568826
TI  - Ventricular tachycardia in ischemic heart disease substrates.
AB  - Advances in the treatment of myocardial infarction (MI) have improved survival
      after ischemic cardiac injury. Post-infarct structural and functional remodeling
      results in electrophysiologic substrates at risk for monomorphic ventricular
      tachycardia (MMVT). Characterization of this substrate using a variety of
      clinical and investigative tools has improved our understanding of MMVT circuits,
      and has accelerated the development of device and catheter-based therapies aimed
      at identification and elimination of this arrhythmia. This review will discuss
      the central role of the ischemic heart disease substrate in the development MMVT.
      Electrophysiologic characterization of the post-infarct myocardium using bipolar
      electrogram amplitudes to delineate scar border zones will be reviewed.
      Functional electrogram determinants of reentrant circuits such as isolated late
      potentials will be discussed. Strategies for catheter ablation of reentrant
      ventricular tachycardia, including structural and functional targets will also be
      examined, as will the role of the epicardial mapping and ablation in the
      management of recurrent MMVT. 

PMID- 24568828
TI  - Sudden cardiac death--historical perspectives.
AB  - Sudden cardiac death (SCD) is an unexpected death due to cardiac causes that
      occurs in a short time period (generally within 1 h of symptom onset) in a person
      with known or unknown cardiac disease. It is believed to be involved in nearly a
      quarter of human deaths, with ventricular fibrillation being the most common
      mechanism. It is estimated that more than 7 million lives per year are lost to
      SCD worldwide. Historical perspectives of SCD are analyzed with a brief
      description on how the developments in the management of sudden cardiac arrest
      evolved over time. 

PMID- 24568829
TI  - Radio frequency ablation for VT--a cost-effective tool to combat SCD in
      developing countries.

PMID- 24568827
TI  - Sudden cardiac death in patients with nonischemic cardiomyopathy.
AB  - Sudden cardiac death (SCD) is an important cause of mortality worldwide. Although
      SCD is most often associated with coronary heart disease, the risk of SCD in
      patients without ischemic heart disease is well-established. Nonischemic
      cardiomyopathies, including idiopathic dilated cardiomyopathy, hypertrophic
      cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy represent
      three unique disease entities that have been shown to be highly associated with
      SCD and ventricular arrhythmias. A variety of risk stratification tools have been
      investigated, although the optimal strategy remains unknown. Identification of
      the arrhythmogenic substrate and treatment of ventricular arrhythmias in these
      subgroups can be challenging. Herein, we aim to discuss the current understanding
      of the anatomic and electrophysiologic substrate underlying ventricular
      arrhythmias and highlight features that may be associated with a higher risk of
      SCD in these 3 conditions. 

PMID- 24568831
TI  - Genetic testing to predict sudden cardiac death: current perspectives and future
      goals.
AB  - It is known that monogenic traits may predispose young and otherwise healthy
      individuals to die suddenly. Diseases such as Long QT Syndrome, Brugada Syndrome
      and Arrhythmogenic Right Ventricular Cardiomyopathy are well known causes of
      arrhythmic death in young individuals. For several years the concept of "genetic
      predisposition" to sudden cardiac death has been limited to these uncommon
      diseases. In the last few years clinical data have supported the view that risk
      of dying suddenly may cluster in families, supporting the hypothesis of a genetic
      component for sudden cardiac death. In this review I will try to provide an
      overview of current knowledge about genetics of sudden death. I will approach
      this topic by discussing first where we stand in the use of genetics for risk
      stratification and therapy selection in monogenic diseases and I will then move
      to discuss the contribution of genetics to patient profiling in acquired
      cardiovascular diseases. 

PMID- 24568830
TI  - Inherited arrhythmia syndromes leading to sudden cardiac death in the young: a
      global update and an Indian perspective.
AB  - Inherited primary arrhythmias, namely congenital long QT syndrome, Brugada
      syndrome and catecholaminergic polymorphic ventricular tachycardia, account for a
      significant proportion of sudden cardiac deaths in young and apparently healthy
      individuals. Genetic testing plays an integral role in the diagnosis, risk
      stratification and treatment of probands and family members. It is increasingly
      obvious that collaborative efforts are required to understand and manage these
      relatively rare but potentially lethal diseases. This article aims to update
      readers on the recent developments in our knowledge of inherited arrhythmias and
      to lay the foundation for a national synergistic effort to characterize them in
      the Indian population. 

PMID- 24568832
TI  - Cardiac imaging in evaluating patients prone to sudden death.
AB  - Identifying subjects who are at risk for SCD and stratifying them correctly into
      low or high-risk groups is the holy grail of Cardiology. While imaging shows a
      lot of promise, it is plagued by the fact that most SCD occurs in relatively
      healthy subjects, a massive group who would not ordinarily be subjected to
      imaging. Left ventricular ejection fraction (LVEF) currently is our primary
      parameter for risk stratification for sudden cardiac death but is a poor marker
      with low sensitivity and specificity. Current data shows that sophisticated
      imaging with techniques, mainly Cardiac magnetic resonance Imaging (CMR), have
      the potential to identify novel high-risk markers underlying SCD, beyond ejection
      fraction. Imaging seems to further refine risk in patients with low LVEF as well
      as in those with normal EF; this is a major strength of advanced imaging.
      Clinical application has been slow and not fully prime time. It is important to
      remember that while promising, imaging techniques including CMR, have not been
      tested in rigorous prospective studies and thus have not as yet replaced EF as
      the gatekeeper to ICD implantation. 

PMID- 24568833
TI  - Tools for risk stratification of sudden cardiac death: a review of the literature
      in different patient populations.
AB  - While various modalities to determine risk of sudden cardiac death (SCD) have
      been reported in clinical studies, currently reduced left ventricular ejection
      fraction remains the cornerstone of SCD risk stratification. However, the
      absolute burden of SCD is greatest amongst populations without known cardiac
      disease. In this review, we summarize the evidence behind current guidelines for
      implantable cardioverter defibrillator (ICD) use for the prevention of SCD in
      patients with ischemic heart disease (IHD). We also evaluate the evidence for
      risk stratification tools beyond clinical guidelines in the general population,
      patients with IHD, and patients with other known or suspected medical conditions.

PMID- 24568834
TI  - Relevance of guideline-based ICD indications to clinical practice.
AB  - The implantable cardioverter-defibrillator (ICD) has established itself as life
      saving therapy in patients at risk for sudden cardiac death. Remarkable
      technological advances have made ICDs easier and safer to implant, with improved
      therapeutic and diagnostic functions and reduced morbidity. Guidelines on ICD
      indications have been proposed by American and European scientific societies
      since a number of years, based upon trials and expert opinion. In the context of
      variable economic and political constraints, it is questionable whether these
      guidelines may be applied to all settings. This review discusses the guideline
      based indications, critically examines their applicability to clinical practice,
      and discusses alternatives to ICD therapy. 

PMID- 24568835
TI  - ICD programming.
AB  - BACKGROUND: Appropriate ICD programming is the key to prevent inappropriate shock
      delivery, that is closely associated to a negative patients' outcome. METHODS:
      Review of the literature on ICD therapy to generate ICD programmings that can be
      applied to the broad population of ICD and CRT-D carriers. RESULTS: Arrhythmia
      detection should occur with a detection time ranging 9"-12" in the VF zone, and
      15"-60" in the VT zone. Discriminator should be applied at least up to 200 bpm.
      ATP therapy is applied to all VTs up to 250 bpm, with a success rate of 70%.
      Inappropriate shocks should occur in <3.6% of patients. CONCLUSION: Tailored ICD
      programming can be achieved following evidence from large ICD trials. Pre-defined
      settings that are saved on the programmer and that can be uploaded at device
      implantation help to ensure optimal programming and to avoid random errors.

PMID- 24568836
TI  - Prognostic factors in primary salivary gland mucoepidermoid carcinoma: an
      analysis of 376 cases in an Eastern Chinese population.
AB  - Mucoepidermoid carcinoma (MEC) is an infrequent malignant neoplasm that
      originates most commonly in the salivary glands. The present study aimed to
      provide new information on prognostic factors in patients with salivary gland
      MEC. A retrospective analysis of the medical records of patients diagnosed with
      primary salivary gland MEC between 2003 and 2010 was conducted. The incidence of
      MEC in the minor salivary glands (62.2%) was almost twice that in the major
      salivary glands (37.8%). The most frequently affected sites were the parotid
      gland and palate. Lymph node metastasis was reported more frequently in male than
      female patients (P = 0.02), in high-grade than low/intermediate grade lesions (P
      < 0.001), and in lesions involving the submandibular gland (P < 0.001). The
      disease-free survival (DFS) at 5 years was 80.47%, with rates of 98.0%, 86.5%,
      and 38.5% for low-, intermediate-, and high-grade tumours, respectively. Among
      various clinicopathological factors, the only independent prognostic factor was
      histological grade (P < 0.001). Primary tumour site and histological grade are
      two important factors affecting cervical lymph node metastasis. Histological
      grade is the only independent factor affecting survival beyond tumor lymph node
      metastasis (TNM) staging in salivary gland MEC. Further advances in therapy are
      needed to improve the outcomes for patients with high-grade lesions.

PMID- 24568838
TI  - Smoking ban in cars will benefit disadvantaged children most.

PMID- 24568837
TI  - Variability in phenylalanine control predicts IQ and executive abilities in
      children with phenylketonuria.
AB  - A number of studies have revealed significant relationships between cognitive
      performance and average phenylalanine (Phe) levels in children with
      phenylketonuria (PKU), but only a few studies have been conducted to examine the
      relationships between cognitive performance and variability (fluctuations) in Phe
      levels. In the current study, we examined a variety of indices of Phe control to
      determine which index best predicted IQ and executive abilities in 47 school-age
      children with early- and continuously-treated PKU. Indices of Phe control were
      mean Phe, the index of dietary control, change in Phe with age, and several
      indices of variability in Phe (standard deviation, standard error of estimate,
      and percentage of spikes). These indices were computed over the lifetime and
      during 3 developmental epochs (<5, 5.0-9.9, and >=10 years of age). Results
      indicated that variability in Phe was generally a stronger predictor of cognitive
      performance than other indices of Phe control. In addition, executive performance
      was better predicted by variability in Phe during older than younger
      developmental epochs. These results indicate that variability in Phe should be
      carefully controlled to maximize cognitive outcomes and that Phe control should
      not be liberalized as children with PKU age.

PMID- 24568839
TI  - Isomers of Dechlorane Plus in an aquatic environment in a highly industrialized
      area in Southern China: spatial and vertical distribution, phase partition, and
      bioaccumulation.
AB  - Dechlorane Plus (DP) was determined in aquatic environment including sediment,
      sediment core, water, and fish species in a highly industrialized area in Pearl
      River Delta, South China. DP was analyzed in sediments and water at concentration
      ranging from 0.08 to 19.4 ng/g dry weight and from 0.24 to 0.78 ng/L,
      respectively. DP was detected in 80% of fish samples with concentration between
      undetectable level to 189 ng/g lipid weight. DP levels were significantly higher
      in the top layer (depth less than 36 cm with concentration ranging from 0.35 to
      57.6 ng/g) than in the lower section (concentration ranging from 0.02 to 0.72
      ng/g), indicating an increase in DP contamination in recent years. The fraction
      of anti-DP in the sediment and water are close to that in the technical mixtures
      implying no stereospecific degradation occurring. An enrichment of syn-DP was
      observed in three fish species suggesting that a stereospecific metabolism of
      anti-DP and/or stereoselective uptake of syn-DP occurring in fish species. The
      calculated BSAFs are 0.024, 0.037, and 0.10 for DP, in mud carp, nile tilapia,
      and plecostomus, respectively, suggesting relatively low bioavailability of DP
      isomers in the sediments.

PMID- 24568841
TI  - Presence of Nosema ceranae associated with honeybee queen introductions.
AB  - Microsporidiosis caused by Nosema species is one of the factors threatening the
      health of the honeybee (Apis mellifera), which is an essential element in
      agriculture mainly due to its pollination function. The dispersion of this
      pathogen may be influenced by many factors, including various aspects of
      beekeeping management such as introduction of queens with different origin.
      Herein we study the relation of the presence and distribution of Nosema spp. and
      the replacement of queens in honeybee populations settled on the Atlantic Canary
      Islands. While Nosema apis has not been detected, an increase of the presence and
      distribution of Nosema ceranae during the last decade has been observed in
      parallel with a higher frequency of foreign queens. On the other hand, a
      reduction of the number of N. ceranae positive colonies was observed on those
      islands with continued replacement of queens. We suggest that such replacement
      could help maintaining low rates of Nosema infection, but healthy queens native
      to these islands should be used in order to conserve local honeybee diversity. 

PMID- 24568840
TI  - Association of IL33-IL-1 receptor-like 1 (IL1RL1) pathway polymorphisms with
      wheezing phenotypes and asthma in childhood.
AB  - BACKGROUND: Genome-wide association studies identified IL33 and IL-1 receptor
      like 1 (IL1RL1)/IL18R1 as asthma susceptibility loci. IL33 and IL1RL1 constitute
      a single ligand-receptor pathway. OBJECTIVE: In 2 birth cohorts, the Prevalence
      and Incidence of Asthma and Mite Allergy (PIAMA) study and Avon Longitudinal
      Study of Parents and Children (ALSPAC), we analyzed associations of longitudinal
      wheezing phenotypes and asthma with single nucleotide polymorphisms (SNPs) of 8
      genes encoding IL-33, IL1RL1, its coreceptor IL1RAcP, its adaptors myeloid
      differentiation primary response gene 88 (MyD88) and Toll-IL-11 receptor domain
      containing adaptor protein (TIRAP), and the downstream IL-1 receptor-associated
      kinase 1, IL-1 receptor-associated kinase 4, and TNF receptor-associated factor 6
      (TRAF6). Furthermore, we investigated whether SNPs in this pathway show
      replicable evidence of gene-gene interaction. METHODS: Ninety-four SNPs were
      investigated in 2007 children in the PIAMA study and 7247 children in ALSPAC.
      Associations with wheezing phenotypes and asthma at 8 years of age were analyzed
      in each cohort and subsequently meta-analyzed. Gene-gene interactions were
      assessed through model-based multifactor dimensionality reduction in the PIAMA
      study, and gene-gene interactions of 10 SNP pairs were further evaluated.
      RESULTS: Intermediate-onset wheeze was associated with SNPs in several genes in
      the IL33-IL1RL1 pathway after applying multiple testing correction in the meta
      analysis: 2 IL33 SNPs (rs4742170 and rs7037276), 1 IL-1 receptor accessory
      protein (IL1RAP) SNP (rs10513854), and 1 TRAF6 SNP (rs5030411). Late-onset wheeze
      was associated with 2 IL1RL1 SNPs (rs10208293 and rs13424006), and persistent
      wheeze was associated with 1 IL33 SNP (rs1342326) and 1 IL1RAP SNP (rs9290936).
      IL33 and IL1RL1 SNPs were nominally associated with asthma. Three SNP pairs
      showed interaction for asthma in the PIAMA study but not in ALSPAC. CONCLUSIONS:
      IL33-IL1RL1 pathway polymorphisms are associated with asthma and specific
      wheezing phenotypes; that is, most SNPs are associated with intermediate-onset
      wheeze, a phenotype closely associated with sensitization. We speculate that IL33
      IL1RL1 pathway polymorphisms affect development of wheeze and subsequent asthma
      through sensitization in early childhood.

PMID- 24568843
TI  - Deoxynivalenol: a trigger for intestinal integrity breakdown.
AB  - Disintegration of the colonic epithelial barrier is considered a key event in the
      initiation and progression of inflammatory bowel and celiac disease. As the
      primary etiology of these diseases remains unknown, we hypothesized that the
      trichothecene deoxynivalenol (DON), a fungal metabolite found in grain-based
      human diets, might be one of the triggers resulting in an impairment of the
      intestinal tight junction network preceding an inflammatory response. Using
      horizontal impedance measurements, we demonstrate that DON disintegrates a human
      Caco-2 cell monolayer within <1 h after exposure to concentrations as low as 1.39
      MUM. This initial trigger is followed by a decrease in transepithelial resistance
      and an increased permeability of marker molecules, such as lucifer yellow and
      FITC-labeled dextran. In parallel, the increase in paracellular transport of FITC
      dextran is demonstrated in vivo in B6C3F1 mice, challenged orally with DON. In
      vitro claudin protein levels are decreased and correlated with a displacement
      within the cells in vitro and in vivo, accompanied by a compensatory up
      regulation of mRNA levels of claudins and their binding partner ZO-1. In treated
      mice, alterations in villus architecture in the entire intestinal tract resemble
      the disintegration of the epithelial barrier, a characteristic of chronic
      inflammatory bowel disease.

PMID- 24568845
TI  - Spectroscopic study of the experimental parameters controlling the structural
      properties of chitosan-Ag nanoparticles composite.
AB  - Chitosan as reducing, stabilizing and capping agent was used to synthesize
      chitosan-silver nanoparticles composite under different experimental conditions
      of temperature or time. The UV-Vis spectra exhibited a single peak at 430nm which
      provided strong evidence for the formation of surface plasmon resonance (SPR)
      band of Ag nanoparticles. The rate of the increase of this absorbance with
      temperature increases with increasing the time of reduction. It was found that
      the variation of the temperature from 60 degrees C to 100 degrees C and the time
      of reduction from 6h to 16h resulted in no significant changes in the intensities
      and positions of the FTIR absorption bands of the composite. The TEM micrographs
      showed distinct typical spherical silver nanoparticles separated from each other
      quite well at reduction temperature range (60-80 degrees C) and displayed some of
      accumulations at high temperature range (90-100 degrees C). The TEM micrographs
      investigation indicated various shapes with different reduction time. The SEM
      images of the prepared samples were discussed. 

PMID- 24568842
TI  - Human biliverdin reductase-based peptides activate and inhibit glucose uptake
      through direct interaction with the kinase domain of insulin receptor.
AB  - Insulin binding changes conformation of the insulin receptor kinase (IRK) domain
      and initiates glucose uptake through the insulin, IGF-1, phosphatidyl inositol 3
      kinase (PI3K), and MAPK pathways; human biliverdin reductase (hBVR) is an IRK
      substrate and pathway effector. This is the first report on hBVR peptide-mediated
      IRK activation and conformational change. (290)KYCCSRK, which increased IRK
      V(max) without changing K(m), stimulated glucose uptake and potentiated insulin
      and IGF-1 stimulation in 4 cell lines. KYCCSRK in native hBVR was necessary for
      the hBVR and IRK cross-activation. Peptide treatment also activated PI3K
      downstream effectors, Akt and ERK, phosphorylation, and Elk transcriptional
      activity. In cells transfected with CMV-regulated EGFP-VP-peptide plasmid, C(292)
      >A mutant did not stimulate glucose uptake; K(296)->A decreased uptake and kinase
      activity. KEDQYMKMTV, corresponding to hBVR's SH2-binding domain, was a potent
      inhibitor of glucose uptake and IRK. The mechanism of action of peptides was
      examined using cells expressing IRK (aa 988-1263) activated by coexpressed
      KYCCSRK. Three active cys-mutants of IRK, with fluorophore coupled to cysteines,
      C(1056), C(1138), or C(1234), were examined for changes in fluorescence emission
      spectra in the presence of peptides. KYCCSRK and KEDQYMKMTV bound to different
      sites in IRK. The findings identify novel agents for activating or inhibiting
      insulin signaling and offer a new approach for treatment of type 2 diabetes and
      hypoglycemia.

PMID- 24568844
TI  - Valuing patients' experiences of healthcare processes: towards broader
      applications of existing methods.
AB  - Healthcare policy leaders internationally recognise that people's experiences of
      healthcare delivery are important, and invest significant resources to monitor
      and improve them. However, the value of particular aspects of experiences of
      healthcare delivery - relative to each other and to other healthcare outcomes -
      is unclear. This paper considers how economic techniques have been and might be
      used to generate quantitative estimates of the value of particular experiences of
      healthcare delivery. A recently published conceptual map of patients' experiences
      served to guide the scope and focus of the enquiry. The map represented both what
      health services and staff are like and do and what individual patients can feel
      like, be and do (while they are using services and subsequently). We conducted a
      systematic search for applications of economic techniques to healthcare delivery.
      We found that these techniques have been quite widely used to estimate the value
      of features of healthcare systems and processes (e.g. of care delivery by a nurse
      rather than a doctor, or of a consultation of 10 minutes rather than 15 minutes),
      but much less to estimate the value of the implications of these features for
      patients personally. To inform future research relating to the valuation of
      experiences of healthcare delivery, we organised a workshop for key stakeholders.
      Participants undertook and discussed 'exercises' that explored the use of
      different economic techniques to value descriptions of healthcare delivery that
      linked processes to what patients felt like and were able to be and do. The
      workshop identified a number of methodological issues that need careful
      attention, and highlighted some important concerns about the ways in which
      quantitative estimates of the value of experiences of healthcare delivery might
      be used. However the workshop confirmed enthusiasm for efforts to attend directly
      to the implications of healthcare delivery from patients' perspectives, including
      in terms of their capabilities.

PMID- 24568846
TI  - Synthesis, characterization, optical properties and theoretical calculations of 6
      fluoro coumarin.
AB  - 6-Fluoro coumarin is synthesized and characterized by (1)H NMR and (13)C NMR. The
      optical properties of the title compound are investigated by UV-vis absorption
      and fluorescence emission spectra, the results show the title compound can absorb
      UV-vis light at 319, 269 and 215nm, moreover it exhibits blue-purple fluorescence
      emission at 416nm. Theoretical studies on molecular structure, infrared spectra
      (IR), nuclear magnetic resonance ((1)H NMR, (13)C NMR) chemical shifts, UV-vis
      absorption and fluorescence emission of the synthesized compound have been worked
      out. Most chemical calculations were performed by density functional theory (DFT)
      method at the B3LYP/6-311G(d,p) level (NMR at B3LYP/Aug-CC-Pvdz level) using
      Gaussian 09 program. The compared results reveal that the scaled theoretical
      vibrational frequencies are in good accordance with the observed spectra;
      computational chemical shifts are consistent with the experimental values in most
      parts, except for some minor deviations; the UV-vis absorption calculated matches
      the experimental one very well, and the fluorescence emission spectrum is in good
      agreement with the experimental one when the solute-solvent hydrogen-bonding
      interaction is considered. These good coincidences prove that the computational
      methods selected can be used to predict these properties of other similar
      materials where it is difficult to arrive at experimental results. 

PMID- 24568847
TI  - Spectrophotometric investigation on the kinetics of oxidation of adrenaline by
      dioxygen of MU-dioxytetrakis(histidinato)-dicobalt(II) complex.
AB  - The cobalt(II)histidine complex binds molecular oxygen reversibly to form an
      oxygen adduct complex, MU-dioxytetrakis-(histidinato)dicobalt(II). The molecular
      oxygen can be released from the oxygenated complex by heating it or by passing
      N2, He or Ar gas through its solution. MU-Dioxytetrakis-(histidinato)dicobalt(II)
      complex oxidizes adrenaline into leucoadrenochrome at 25 degrees C while at
      higher temperature (>40 degrees C) adrenochrome with lambdamax at 490nm is
      formed. The rate of formation of leucoadrenochrome was found to be independent of
      [bis(histidinato)cobalt(II)]. The rate of reaction for the formation of
      leucoadrenochrome and adrenochrome increased with the increase in [adrenaline] at
      its lower concentration but become independent at higher concentration.
      Similarly, the rate of formation of both leucoadrenochrome and adrenochrome was
      linearly dependent upon [NaOH]. The values of activation parameters i.e. DeltaEa,
      DeltaH(?) and DeltaS(?) for the formation of leucoadrenochrome are reported. 

PMID- 24568848
TI  - Quantum dots as a possible oxygen sensor.
AB  - Results of studies on optical properties of low toxicity quantum dots (QDs)
      obtained from copper doped zinc sulfate are discussed in the paper. The effect of
      copper admixture concentration and solution pH on the fluorescence emission
      intensity of QDs was investigated. Quenching of QDs fluorescence by oxygen was
      reported and removal of the oxygen from the environment by two methods was
      described. In the chemical method oxygen was eliminated by adding sodium sulfite,
      in the other method oxygen was removed from the solution using nitrogen gas. For
      elimination of oxygen by purging the solution with nitrogen the increase of
      fluorescence intensity with decreasing oxygen concentration obeyed Stern-Volmer
      equation indicating quenching. For the chemical method Stern-Volmer equation was
      not fulfilled. The fluorescence decays lifetimes were determined and the increase
      of mean lifetimes at the absence of oxygen support hypothesis that QDs
      fluorescence is quenched by oxygen. 

PMID- 24568849
TI  - [Illness associated malnutrition - a medical and health policy important topic].

PMID- 24568850
TI  - [Epidemiology of malnutrition].
AB  - The World Health Organisation classifies malnutrition worldwide as the greatest
      threat to public health. An expert report of the Council of Europe clearly showed
      that malnutrition in hospitalised patients is a real existing problem in all
      European countries, including Switzerland. According to the literature,
      malnutrition is prevalent in 20 - 60 % of patients on hospital admission.
      Malnutrition increases with age and is found more and more in obese subjects.
      Unintentional weight loss is the main feature of disease-related malnutrition in
      normalweight and obese individuals. The nutritional problem in obese persons
      manifests itself through nutrient imbalances and micronutrient deficiency. The
      cause for nutritional deficiencies is a hypercaloric diet with its energy -
      dense, but qualitative low - value foods. Depending on the extent of obesity,
      certain micronutrients are to be critically evaluated. It has been proven that
      for instance the vitamin D and iron metabolism are pathologically impaired by the
      increased fatty tissue. In Switzerland, the proportion of people under 20 years
      has decreased from 40.7 % (1900) to 20.6 % (2011), whereas in the elderly over 64
      years, an increase from 5.8 % to 17.2 % has been recorded. In the very elderly
      people over 80 years, the increase from 0.5 % to 4.8 % has been particularly
      pronounced. Because malnutrition increases with age, it will be an important
      issue in the future and hospitals, nursing homes and home care will be
      particularly affected. 

PMID- 24568851
TI  - [nutritionDay- an annual cross-sectional audit of nutrition in healthcare].
AB  - nutritionDay is a worldwide project to determine prevalence of symptoms of
      malnutrition and reduced nutrient intake as well as risk factors and outcome.
      Individual units can benchmark their data against data from the reference
      database of the same specialty. Questionnaires are available in 32 languages.
      151'666 patients from 4'877 units in 51 countries have participated between 2006 
      2012. In hospitals 8.1 % had a BMI < 18.5, 45.4 % indicated having lost weight
      and 49.9 % had not eaten normally last week. On nutritionDay 41.5 % ate the full
      meal at lunch or dinner and 14 % ate nothing. The odds ratio for death in
      hospital within 30 days was 2.76 [2.50, 3.05] if having lost weight, increased to
      a maximum of 6.17 [5.54, 6.88] with a history of decreased intake last week and
      7.66 [6.72, 8.74] if no intake was found on nutritionDay despite being allowed to
      eat. All factors remained significant in multivariate analysis. The most frequent
      reason for not eating is loss of appetite. Only a maximum of one third of all
      patients that eat nothing receive support with enteral or parenteral nutrition.
      Disease-related undernutrition is very frequent in hospitals and is associated
      with poor outcome. nutritionDay is a measurement tool to determine the prevalence
      of undernutrition and to benchmark regularly nutrition risk factors and level of
      interventions against a large recent reference database. 

PMID- 24568852
TI  - [Causes an clinical sign of malnutrition].
AB  - Malnutrition is a highly relevant independent clinical risk factor with
      scientifically well-proven clinical and economic consequences. The causes of
      malnutrition are complex and multifactorial. Malnutrition is frequently caused by
      medical as well as non-medical social factors as social isolation, inability to
      gain and/or prepare adequate food as well as poverty. Next to loss of body weight
      ongoing malnutrition resulted in a large variety of specific and predominantly
      non-specific symptoms. In patients on risk for malnutrition systematic
      questioning and targeted physical investigation are mandatory to diagnose
      malnutrition at an early stage and to evaluate the individually underlying causes
      in order to guarantee a timely adequate nutritional therapy in those patients. 

PMID- 24568854
TI  - [Oral nutritional supplements are effective, purposeful and economic].
AB  - Numerous studies have shown that medically indicated sip feeding is an effective
      and cost-saving mean to combat malnutrition. Particularly, acutely ill, elderly,
      polymorbid internal and surgical patients benefit from sip feeding. In
      Switzerland, the reimbursement of medically indicated sip feeding at home by the
      compulsory health insurance is critically important for the good of the patient
      and cost optimization. This is particularly true in the longer-term considering
      the demographic trends in Switzerland with an important increase of the elderly
      population. Therefore, the reimbursement of sip feeding was requested from the
      Federal Department of Home Affairs - with success. Since July 2012, medically
      indicated sip feeding at home is covered by the compulsory health insurance
      provided that a medical diagnosis according to the strict and well-defined
      guidelines from the Society for Clinical Nutrition Switzerland (SSCN) is given. 

PMID- 24568855
TI  - [Enteral tube feeding].
AB  - Tube feeding is an integral part of medical therapies, and can be easily managed
      also in the outpatient setting. Tube feeding by the stomach or small intestine
      with nasogastral or nasojejunal tubes is common in clinical practice. Long-term
      nutrition is usually provided through a permanent tube, i. e. a percutaneous
      endoscopic gastrostomy (PEG). Modern portable nutrition pumps are used to cover
      the patient's nutritional needs. Enteral nutrition is always indicated if
      patients can not or should not eat or if nutritional requirements cannot be
      covered within 3 days after an intervention, e. g. after abdominal surgery.
      Industrially produced tube feedings with defined substrate concentrations are
      being used; different compositions of nutrients, such as glutamine fish oil etc.,
      are used dependent on the the condition of the patient. Enteral nutrition may be
      associated with complications of the tube, e. g. dislocation, malposition or
      obstruction, as well as the feeding itself, e. g.hyperglycaemia, electrolyte
      disturbances, refeeding syndrome diarrhea or aspiration). However, the benefit of
      tube feeding usually exceeds the potential harm substantially. 

PMID- 24568853
TI  - [Practical scores for the detection of malnutrition].
AB  - Malnutrition occurs in 30 - 60 % of hospitalized medical or surgical patients, as
      well as out-patients. Serious consequences at various levels were observed.
      Malnutrition influences negatively the quality of life, the immune system, muscle
      strength and worsens the prognosis of the patient. Interventions for a rapid and
      simple identification and effective treatment of this condition are essential and
      cost saving. Screening tools for the identification of patients at nutritional
      risk are very useful in daily practice. The systematic identification of patients
      with potential or apparent malnutrition is very important allowing an effective
      nutritional treatment at an early time. The medical team in charge should perform
      the nutritional risk screening and the following assessment to recognize the
      nutritional problems and to solve them in an interdisciplinary and -professional
      team. 

PMID- 24568856
TI  - [Parenteral nutrition strategies].
AB  - Parenteral nutrition is a fundamental part of any therapeutic concept in
      critically ill patients. Just recently some international prospective randomized
      controlled trials were investigating the correct indication, optimal timing and
      dosage of parenteral nutrition regimens. Despite a controversial discussion newer
      strategies recommend the parenteral nutrition as a very important supplemental
      component to an early enteral nutrition therapy. 

PMID- 24568857
TI  - [Sarcopenia].
AB  - The term sarcopenia stands for the age-related loss of muscle mass and is
      pahophysiologically closely linked to the "frailty syndrome". The search for
      sarcopenia - the combination of both a muscle loss and a reduced muscle function
      or strength - is nowadays part of the comprehensive geriatric assessment in
      Geriatric Medicine. From a pahophysiological point of view, different factors are
      involved as in all geriatric snydromes, but a low-grade inflammatory state is a
      cornerstone in all of them. Differentiation to cachexia is important, as the
      latter is not as amenable to treatment strategies. Many questions including the
      international full acceptance of the defintition of sarcopenia remain open. A
      good example is sarcoepnic obesity, a quantitatively fast increasing challenge in
      elderly persons. 

PMID- 24568858
TI  - [Ethical issues of artificial nutritional support].
AB  - This review article discusses some ethical issues of clinical nutrition according
      to the Beauchamp and Childress principles of bioethics: "respect for autonomy,
      nonmaleficence, beneficence, and justice". 

PMID- 24568859
TI  - [Malnutrition in the era of DRG].
AB  - Malnutrition in hospital patients is of important medical and economic
      significance. The adverse consequences of malnutrition on quality of life and
      many more factors such as morbidity, mortality, tolerance of treatments and
      length of hospital stay are well documented in the medical literature.
      Nevertheless, the effects of malnutrition are still often underestimated and
      hence malnutrition is not recognised as a distinct diagnosis. Moreover,
      malnutrition is rarely documented in medical reports and often not adequately
      treated with adverse effects. The reason for this neglectfulness are diverse, e.
      g. inadequate training of doctors and nurses in clinical nutrition and lack of
      sensibilisation of the hospital staff for the problem of malnutrition. Therefore,
      a systematic screening for malnutrition is rarely undertaken in Swiss hospitals.
      The introduction of the Swiss-DRG system (DRG, diagnosis related groups) in
      January 2012 gave the chance to boost recording and to document malnutrition in a
      standardised way in the patient history, and to code precisely malnutrition as a
      distinct diagnosis. Moreover, this approach allowed to document the specific
      nutritional therapy. Here, we describe the way of documenting and coding
      malnutrition in the Swiss-DRG system and the medical and economic consequences of
      this procedure. 

PMID- 24568861
TI  - Receptors, cells and circuits involved in pruritus of systemic disorders.
AB  - Pruritus is a sensory phenomenon accompanying a broad range of systemic disorders
      including hematologic and lymphoproliferative disorders, metabolic and endocrine
      diseases, solid tumours, and infectious diseases. The molecular mechanisms
      involved in itch sensation remain enigmatic in most of these diseases. However,
      from studies in patients and animal models a large number of mediators and
      receptors responsible for scratching behaviour have been identified in recent
      years. New insights into the interplay between neuronal and non-neuronal cells in
      the initiation, modulation and sensitization of itch sensation have been
      acquired. This review highlights the current knowledge of the molecular mechanism
      involved in pruritus of systemic disorders and summarizes the signalling pathways
      of biogenic amines, neuropeptides, proteases, eicosanoids, cytokines, opioids,
      endocannabinoids, neurotrophins, phospholipids and other signalling molecules
      participating in pruritus. 

PMID- 24568862
TI  - Differential role of molten globule and protein folding in distinguishing unique
      features of botulinum neurotoxin.
AB  - Botulinum neurotoxins (BoNTs) are proteins of great interest not only because of
      their extreme toxicity but also paradoxically for their therapeutic applications.
      All the known serotypes (A-G) have varying degrees of longevity and potency
      inside the neuronal cell. Differential chemical modifications such as
      phosphorylation and ubiquitination have been suggested as possible mechanisms for
      their longevity, but the molecular basis of the longevity remains unclear. Since
      the endopeptidase domain (light chain; LC) of toxin apparently survives inside
      the neuronal cells for months, it is important to examine the structural features
      of this domain to understand its resistance to intracellular degradation.
      Published crystal structures (both botulinum neurotoxins and endopeptidase
      domain) have not provided adequate explanation for the intracellular longevity of
      the domain. Structural features obtained from spectroscopic analysis of LCA and
      LCB were similar, and a PRIME (PReImminent Molten Globule Enzyme) conformation
      appears to be responsible for their optimal enzymatic activity at 37 degrees C.
      LCE, on the other hand, was although optimally active at 37 degrees C, but its
      active conformation differed from the PRIME conformation of LCA and LCB. This
      study establishes and confirms our earlier finding that an optimally active
      conformation of these proteins in the form of PRIME exists for the most poisonous
      poison, botulinum neurotoxin. There are substantial variations in the structural
      and functional characteristics of these active molten globule related structures
      among the three BoNT endopeptidases examined. These differential conformations of
      LCs are important in understanding the fundamental structural features of
      proteins, and their possible connection to intracellular longevity could provide
      significant clues for devising new countermeasures and effective therapeutics. 

PMID- 24568860
TI  - Role of mitochondria in mutant SOD1 linked amyotrophic lateral sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with an
      adult onset characterized by loss of both upper and lower motor neurons. In ~10%
      of cases, patients developed ALS with an apparent genetic linkage (familial ALS
      or fALS). Approximately 20% of fALS displays mutations in the SOD1 gene encoding
      superoxide dismutase 1. There are many proposed cellular and molecular mechanisms
      among which, mitochondrial dysfunctions occur early, prior to symptoms
      occurrence. In this review, we modeled the effect of mutant SOD1 protein via the
      formation of a toxic complex with Bcl2 on mitochondrial bioenergetics.
      Furthermore, we discuss that the shutdown of ATP permeation through mitochondrial
      outer membrane could lead to both respiration inhibition and temporary
      mitochondrial hyperpolarization. Moreover, we reviewed mitochondrial calcium
      signaling, oxidative stress, fission and fusion, autophagy and apoptosis in
      mutant SOD1-linked ALS. Functional defects in mitochondria appear early before
      symptoms are manifested in ALS. Therefore, mitochondrial dysfunction is a
      promising therapeutic target in ALS.

PMID- 24568863
TI  - Energy cost for the proper ionization of active site residues in 6
      phosphogluconate dehydrogenase from T. brucei.
AB  - The catalytic mechanism of 6-phosphogluconate dehydrogenase requires the
      inversion of a Lys/Glu couple from its natural ionization state. The pKa of these
      residues in free and substrate bound enzymes has been determined measuring by ITC
      the proton release/uptake induced by substrate binding at different pH values. Wt
      6-phosphogluconate dehydrogenase from Trypanosoma brucei and two active site
      enzyme mutants, K185H and E192Q were investigated. Substrate binding was
      accompanied by proton release and was dependent on the ionization of a group with
      pKa 7.07 which was absent in the E192Q mutant. Kinetic data highlighted two pKa,
      7.17 and 9.64, in the enzyme-substrate complex, the latter being absent in the
      E192Q mutant, suggesting that the substrate binding shifts Glu192 pKa from 7.07
      to 9.64. A comparison of wt and E192Q mutant appears to show that the substrate
      binding shifts Lys185 pKa from 9.9 to 7.17. By comparing differences in proton
      release and the binding enthalpy of wt and mutant enzymes, the enthalpic cost of
      the change in the protonation state of Lys185 and Glu192 was estimated at
      ~6.1kcal/mol. The change in protonation state of Lys185 and Glu192 has little
      effect on Gibbs free energy, 240-325cal/mol. However proton balance evidences the
      dissociation of other group(s) that can be collectively described by a single pKa
      shift from 9.1 to 7.54. This further change in ionization state of the enzyme
      causes an increase of free energy with a total cost of 1.2-2.3kcal/mol to set the
      enzyme into a catalytically competent form. 

PMID- 24568865
TI  - Unraveling Brain Functional Connectivity of encoding and retrieval in the context
      of education.
AB  - Human memory is an enigmatic component of cognition which many researchers have
      attempted to comprehend. Accumulating studies on functional connectivity see
      brain as a complex dynamic unit with positively and negatively correlated
      networks in perfect coherence during a task. We aimed to examine coherence of
      network connectivity during visual memory encoding and retrieval in the context
      of education. School Educated (SE) and College Educated (CE) healthy volunteers
      (n=60) were recruited and assessed for visual encoding and retrieval. Functional
      connectivity using seed to voxel based connectivity analysis of the posterior
      cingulate cortex (PCC) was evaluated. We noticed that there were reciprocal
      dynamic changes in both dorsolateral prefrontal cortex (DLPFC) region and PCC
      regions during working memory encoding and retrieval. In agreement with the
      previous studies, there were more positively correlated regions during retrieval
      compared to encoding. The default mode network (DMN) networks showed greater
      negative correlations during more attentive task of visual encoding. In tune with
      the recent studies on cognitive reserve we also found that number of years of
      education was a significant factor influencing working memory connectivity. SE
      had higher positive correlation to DLPFC region and lower negative correlation to
      DMN in comparison with CE during encoding and retrieval. 

PMID- 24568866
TI  - The cost-effectiveness of ulipristal acetate tablets in treating patients with
      moderate to severe symptoms of uterine fibroids.
AB  - OBJECTIVES: Ulipristal acetate is a selective progesterone receptor modulator
      that has been demonstrated to be an effective 3-month pre-operative treatment for
      moderate to severe symptoms of uterine fibroids in adult women of reproductive
      age. The aim of this analysis was to assess the cost-effectiveness of 5mg
      ulipristal as an add-on therapy to standard pre-surgical observation and
      treatment in Hungary. STUDY DESIGN: A Markov model was developed using a 10-year
      time horizon. Ulipristal was compared with pre-surgical observation and immediate
      hysterectomy. The model comprised the following mutually exclusive health states:
      mild, moderate, severe, or persistent severe excessive bleeding disorder;
      myomectomy; post-myomectomy with mildly to moderately excessive bleeding
      disorder; post-myomectomy with severely excessive bleeding disorder;
      hysterectomy; post-hysterectomy; post-menopause; and death. Transition
      probabilities and utility values were obtained from clinical trials and the
      scientific literature. Resource utilisation and unit costs were derived from a
      consensus panel of clinical experts, National Health Insurance Fund tariffs, and
      publications. RESULTS: Adding a 3-month course of ulipristal to pre-operative
      observation was predicted to achieve an additional 0.021 quality-adjusted life
      years (QALYs) at an estimated incremental cost of ?397, which would result in an
      incremental cost of ?19,200/QALY. When 3 months of ulipristal therapy was
      compared with immediate hysterectomy, the incremental cost-effectiveness ratio
      was reduced to ?3575/QALY. The results were most sensitive to the utility value
      of the post-hysterectomy health state but responsive to changes in other model
      parameters. CONCLUSIONS: The results of this analysis suggest that adding
      ulipristal treatment to standard pre-surgical therapy represents a good value for
      money in Hungary. The inclusion of societal benefits may considerably reduce the
      cost-effectiveness ratio.

PMID- 24568864
TI  - Alterations of the myristoylated, alanine-rich C kinase substrate (MARCKS) in
      prefrontal cortex in schizophrenia.
AB  - Abnormal synaptic plasticity has been implicated in the cognitive deficits seen
      in schizophrenia, where alterations have been found in neurotransmission,
      signaling and dendritic dynamics. Rapid rearrangement of the actin cytoskeleton
      is critical for plasticity and abnormalities of molecular regulators of this
      process are candidates for understanding mechanisms underlying these changes in
      schizophrenia. The myristoylated, alanine-rich C-kinase substrate (MARCKS) is
      crucial for many roles associated with synaptic plasticity, including
      facilitation of neurotransmission, dendritic branching and in turn cognitive
      function. Accordingly, we hypothesized that this protein is abnormally expressed
      or regulated in schizophrenia. We measured protein expression of MARCKS by
      Western blot analysis in postmortem samples of dorsolateral prefrontal cortex
      (DLPFC) from elderly schizophrenia patients (N=16) and a comparison group (N=20).
      We also assayed phosphorylated-MARCKS (pMARCKS), given the role of
      phosphorylation in reversing membrane association by MARCKS. We found decreased
      expression of both MARCKS and pMARCKS in schizophrenia. Altered myristoylation
      may be a mechanism that explains this down-regulation of MARCKS, so we also
      assayed expression of the two isoforms of the key myristoylation enzyme, NMT, and
      an enzymatic inhibitor of this enzyme, NMT-inhibitor protein (NIP71) by Western
      blotting in these same subjects. Expression did not change between groups for
      these proteins, suggesting a mechanism other than myristoylation is responsible
      for decreased MARCKS expression in schizophrenia. These data suggest a potential
      mechanism underlying aspects of altered synaptic plasticity observed in
      schizophrenia. 

PMID- 24568867
TI  - ND4L gene concurrent 10609T>C and 10663T>C mutations are associated with Leber's
      hereditary optic neuropathy in a large pedigree from Kuwait.
AB  - BACKGROUND: Leber's hereditary optic neuropathy (LHON) is a condition
      characterised by a rapid bilateral central vision loss due to death of the
      retinal ganglion cells, leading to visual impairment commonly occurring during
      young adulthood. The disease manifests itself more in male patients than female
      patients. The mtDNA mutations m.11778G>A, m.3460G>A and m.14484T>C are by far
      more frequent in LHON than any other mutation. In this report, a multi
      generational Arab family from Kuwait with 14 male members with LHON was
      investigated. METHODS: Complete mtDNA mutational analysis by direct Sanger's
      sequencing was carried out to detect pathogenic mutations, polymorphisms and
      haplogrouping. RESULTS: All maternally related subjects from this study who were
      examined expressed the L3 haplotype background, with two concurrent mtDNA
      mutations, 10609T>C and 10663T>C, that led to non-conservative amino acid changes
      of Ile47Thr and Val65Ala, respectively. The two variations were absent in 144
      normal and ethnicity-matched controls. CONCLUSIONS: The two identified mutations
      associated with LHON in this family may exert their pathogenicity through a
      cumulative or haplogroup effect. This is the first report of the presence of two
      concurrent mutations in the ND4L gene in individuals with LHON who carry the L3
      haplogroup.

PMID- 24568868
TI  - Pathology detection rate of spectral domain optical coherence tomography devices.
AB  - BACKGROUND: Spectral domain optical coherence tomography (SDOCT) allows for
      higher resolution scans and higher scanning speeds compared to time domain OCT
      (TDOCT). The purpose of this study is to compare the pathology detection rates of
      various SDOCT devices to the Stratus TDOCT. METHODS: Patients with neovascular
      age-related macular degeneration were imaged on the Stratus and one of four SDOCT
      devices. The images were then analysed in a masked manner evaluating for the
      presence of epiretinal membrane (ERM), pigment epithelial detachment (PED) and
      subretinal fluid (SRF). After determining that low scan density with one of the
      devices was likely the cause of missed PED and SRF compared to the other SDOCT
      devices the study was repeated with a higher scan density. RESULTS: 60 eyes from
      60 patients with neovascular macular degeneration were imaged on each SDOCT
      device, for a total of 240 eyes from 240 patients imaged on Stratus. There were
      no instances where pathology was visible on Stratus but was missed on SDOCT. The
      highest incidence of missed pathology was with SRF, followed by ERM and PED.
      CONCLUSIONS: The increased resolution and image quality of SDOCT devices over
      TDOCT allows for finer discrimination of retinal structures. The increased speed
      of SDOCT allows for dense coverage of the macula resulting in the ability to see
      smaller areas of PED and SRF. There was a critical threshold for the distance
      between B-scans in the three-dimensional cube scan for detection of pathology.

PMID- 24568869
TI  - Trans-scleral local resection of toxic choroidal melanoma after proton beam
      radiotherapy.
AB  - AIM: To report on trans-scleral local resection of choroidal melanoma for
      exudative retinal detachment and neovascular glaucoma (toxic tumour syndrome)
      after proton beam radiotherapy (PBR). METHODS: A non-randomised, prospective
      study of secondary trans-scleral local resection of choroidal melanoma for
      exudative retinal detachment with or without neovascular glaucoma after PBR. The
      patients were treated at the Liverpool Ocular Oncology Centre between February
      2000 and April 2008. The trans-scleral local resection was performed with a
      lamellar-scleral flap, using systemic hypotension to reduce haemorrhage. RESULTS:
      12 patients (six women, six men) with a mean age of 51 years (range 20-75) were
      included in this study. The tumour margins extended anterior to ora serrata in
      six patients. On ultrasonography, the largest basal tumour dimension averaged
      12.4 mm (range 6.8-18.1) and the tumour height averaged 7.1 mm (range 4.2-10.7).
      The retinal detachment was total in seven patients. Neovascular glaucoma was
      present in four patients. The time between PBR and local resection had a mean of
      17.4 months (range 1-84). The ophthalmic follow-up time after the local resection
      had a mean of 46.2 months (range 14-99). At the latest known status, the eye was
      conserved in 10 patients, with a flat retina in all these patients and visual
      acuity equal or better than 6/30 in four patients. The reasons for enucleation
      were: patient request for enucleation when rhegmatogenous retinal detachment
      complicated the resection (one patient) and phthisis (one patient). CONCLUSIONS:
      Exudative retinal detachment, rubeosis and neovascular glaucoma after PBR of a
      choroidal melanoma can resolve after trans-scleral local resection of the tumour.
      Our findings suggest that these complications are caused by the persistence of
      the irradiated tumour within the eye ('toxic tumour syndrome').

PMID- 24568871
TI  - 'Dilatation' and 'dilation': trends in use on both sides of the Atlantic.

PMID- 24568872
TI  - Novel splice-site and missense mutations in the ALDH1A3 gene underlying autosomal
      recessive anophthalmia/microphthalmia.
AB  - AIM: This study aimed to identify the underlying genetic defect responsible for
      anophthalmia/microphthalmia. METHODS: In total, two Turkish families with a total
      of nine affected individuals were included in the study. Affymetrix 250 K single
      nucleotide polymorphism genotyping and homozygosity mapping were used to identify
      the localisation of the genetic defect in question. Coding region of the ALDH1A3
      gene was screened via direct sequencing. cDNA samples were generated from primary
      fibroblast cell cultures for expression analysis. Reverse transcriptase PCR (RT
      PCR) analysis was performed using direct sequencing of the obtained fragments.
      RESULTS: The causative genetic defect was mapped to chromosome 15q26.3. A
      homozygous G>A substitution (c.666G>A) at the last nucleotide of exon 6 in the
      ALDH1A3 gene was identified in the first family. Further cDNA sequencing of
      ALDH1A3 showed that the c.666G>A mutation caused skipping of exon 6, which
      predicted in-frame loss of 43 amino acids (p.Trp180_Glu222del). A novel missense
      c.1398C>A mutation in exon 12 of ALDH1A3 that causes the substitution of a
      conserved asparagine by lysine at amino acid position 466 (p.Asn466Lys) was
      observed in the second family. No extraocular findings-except for nevus flammeus
      in one affected individual and a variant of Dandy-Walker malformation in another
      affected individual-were observed. Autistic-like behaviour and mental retardation
      were observed in three cases. CONCLUSIONS: In conclusion, novel ALDH1A3 mutations
      identified in the present study confirm the pivotal role of ALDH1A3 in human eye
      development. Autistic features, previously reported as an associated finding,
      were considered to be the result of social deprivation and inadequate parenting
      during early infancy in the presented families.

PMID- 24568870
TI  - Prevalence and causes of vision loss in sub-Saharan Africa: 1990-2010.
AB  - AIM: To estimate the magnitude, temporal trends and subregional variation in the
      prevalence of blindness, and moderate/severe vision impairment (MSVI) in sub
      Saharan Africa. METHODS: A systematic review was conducted of published and
      unpublished population-based surveys as part of the Global Burden of Disease,
      Risk Factors and Injuries Study 2010. The prevalence of blindness and vision
      impairment by country and subregion was estimated. RESULTS: In sub-Saharan
      Africa, 52 studies satisfied the inclusion criteria. The estimated age
      standardised prevalence of blindness decreased by 32% from 1.9% (95% CI 1.5% to
      2.2%) in 1990 to 1.3% (95% CI 1.1% to 1.5%) in 2010 and MSVI by 25% from 5.3%
      (95% CI 0.2% to 0.3%) to 4.0% (95% CI 0.2% to 0.3%) over that time. However,
      there was a 16% increase in the absolute numbers with blindness and a 28%
      increase in those with MSVI. The major causes of blindness in 2010 were; cataract
      35%, other/unidentified causes 33.1%, refractive error 13.2%, macular
      degeneration 6.3%, trachoma 5.2%, glaucoma 4.4% and diabetic retinopathy 2.8%. In
      2010, age-standardised prevalence of MSVI in Africa was 3.8% (95% CI 3.1% to
      4.7%) for men and 4.2% (95% CI 3.6% to 5.3%) for women with subregional
      variations from 4.1% (95% CI 3.3% to 5.4%) in West Africa to 2.0% (95% CI 1.5% to
      3.3%) in southern Africa for men; and 4.7% (95% CI 3.9% to 6.0%) in West Africa
      to 2.3% (95% CI 1.7% to 3.8%) in southern Africa for women. CONCLUSIONS: The age
      standardised prevalence of blindness and MSVI decreased substantially from 1990
      to 2010, although there was a moderate increase in the absolute numbers with
      blindness or MSVI. Significant subregional and gender disparities exist.

PMID- 24568873
TI  - WINROP can modify ROP screening praxis: a validation of WINROP in populations in
      Sormland and Vastmanland.
AB  - BACKGROUND: This study validates the newly developed WINROP algorithm aimed at
      detecting retinopathy of prematurity (ROP) requiring treatment at an early stage.
      The study was conducted at two middle-sized hospitals in Sweden, prospectively
      and retrospectively. METHODS: A total of 104 children participated in this study.
      Their mean gestational age at birth was 28.7 weeks (range, 23.6-32.1 weeks), and
      their mean birth weight was 1208 g (range, 477-2340 g). Weekly weight
      measurements were used in WINROP to calculate the risk of developing ROP.
      RESULTS: 80% of infants (83/104) had no ROP, 15% (16/104) had mild ROP (stage 1
      or 2), 5% (5/104) had severe ROP, and 2% (2/104) were treated for ROP. The alarm
      was registered at an average of 2 weeks postnatal age (range 1-6 weeks).
      CONCLUSIONS: WINROP identified all the infants at risk for developing stage 3 ROP
      (100% sensitivity) and had a 59% specificity. The alarm was registered several
      weeks before screening for ROP began. WINROP can be used to complement
      conventional ROP screening.

PMID- 24568875
TI  - Cell cycle and nucleomorph division in Pyrenomonas helgolandii (Cryptophyta).
AB  - The cells of cryptophycean and chlorarachniophycean algae contain a nucleomorph,
      a vestigial nucleus derived from red and green algal endosymbionts respectively.
      The origin of the nucleomorph is therefore different from that of cellular
      organelles such as mitochondria and chloroplasts. In this study, we sought to
      determine whether cell cycle regulation of the nucleomorph in the cryptophycean
      alga Pyrenomonas helgolandii is functionally similar to that of the cell nucleus.
      We performed an ultrastructural analysis of nucleomorph division in cells
      prepared by rapid freezing fixation - freeze substitution and also carried out
      BrdU labeling experiments to determine the timing of nucleomorph DNA synthesis in
      relation to that of the cell nucleus. In cells cultured under 16 hours light: 8
      hours dark conditions, BrdU labeling experiments showed that DNA synthesis in the
      nucleomorph occurred during a limited period from 2 hr to 4 hr after the
      beginning of the dark period. The S phase in the nucleomorph started just after
      completion of the nuclear S phase. Thus, DNA synthesis in the nucleomorph
      occurred at a defined period of the cell cycle. By contrast, our BrdU experiments
      showed that the nucleoids of mitochondria and chloroplasts could perform DNA
      synthesis throughout the whole cell cycle.

PMID- 24568874
TI  - The effect of action experience on sensorimotor EEG rhythms during action
      observation.
AB  - A recent line of inquiry has examined how an observer's experience with action
      changes the neural processing of similar actions when they are subsequently
      observed. The current study used electroencephalography (EEG) to test the
      hypothesis that giving participants different types and amounts of experience
      with specific objects would lead to differential patterns of sensorimotor rhythms
      during the observation of similar actions on those objects. While EEG was
      recorded, three groups of participants (n=20 in each group; mean age=22.0 years,
      SD=2.7) watched video clips of an actor reaching, grasping, and lifting two
      objects. Participants then received information about differences in weight
      between the two objects. One group gained this information through extended
      sensorimotor experience with the objects, a second group received much briefer
      sensorimotor experience with the objects, and the third group read written
      information about the objects' weights. Participants then viewed the action
      sequences again. For participants who had sensorimotor experience with the
      objects, the EEG response to viewing the actions was differentially sensitive to
      the anticipated weight of the objects. We conclude that this sensitivity was
      based on the participant's prior sensorimotor experience with the objects. The
      participants who only received semantic information about the objects showed no
      such effects. The primary conclusion is that even brief experience with actions
      affects sensorimotor cortex activity during the subsequent observation of similar
      actions.

PMID- 24568877
TI  - Abnormal functioning of the left temporal lobe in language-impaired children.
AB  - Specific language impairment is associated with enduring problems in language
      related functions. We followed the spatiotemporal course of cortical activation
      in SLI using magnetoencephalography. In the experiment, children with normal and
      impaired language development heard spoken real words and pseudowords presented
      only once or two times in a row. In typically developing children, the activation
      in the bilateral superior temporal cortices was attenuated to the second
      presentation of the same word. In SLI children, this repetition effect was nearly
      nonexistent in the left hemisphere. Furthermore, the activation was equally
      strong to words and pseudowords in SLI children whereas in the typically
      developing children the left hemisphere activation persisted longer for
      pseudowords than words. Our results indicate that the short-term maintenance of
      linguistic activation that underlies spoken word recognition is defective in SLI
      particularly in the left language-dominant hemisphere. The unusually rapid decay
      of speech-evoked activation can contribute to impaired vocabulary growth. 

PMID- 24568878
TI  - Individual and collective responsibility to enhance regulatory compliance of the
      Three Rs.
AB  - Investigators planning to use animals in their research and the Institutional
      Animal Care and Use Committee (IACUC) members who review the research protocols
      must take personal responsibility for ensuring that they have the skills and
      knowledge to perform their duties, applying the Three Rs principles of Russell
      and Burch. The two Korean laws introduced in 2008 and 2009 regulating animal use
      for scientific purposes in line with the Three Rs principles have been revised a
      total of 11 times over the last 6 years. Both regulatory agencies, e.g., the
      Animal and Plant Quarantine Agency and the Ministry of Food and Drug Safety,
      provide regular training based on the legal requirements. Based on the amended
      Animal Welfare Act, the IACUC appointment framework has been upgraded:
      appointments are now for two-year terms and require a qualified training
      certificate issued by the Animal and Plant Quarantine Agency since 2012. The
      authors reviewed the current curricular programs and types of training conducted
      by the two governing agencies through Internet searches. Our Internet survey
      results suggest that: a) diversity should be provided in training curricula,
      based on the roles, backgrounds and needs of the individual trainees; b) proper
      and continued educational programs should be provided, based on trainees'
      experiences; and c) active encouragement by government authorities can improve
      the quality of training curricula.

PMID- 24568876
TI  - Osmotolerance in the Cryptophyceae: jacks-of-all-trades in the Chroomonas Clade.
AB  - No detailed studies have been performed to date on osmotolerance in cryptophytes,
      although one species, Chroomonas africana, had previously been reported to grow
      in freshwater as well as seawater. This study focused on osmotolerance in
      Chroomonas. Growth at different osmolalities and parameters of contractile
      vacuole function were examined and compared across a high-resolution phylogeny.
      Two evolutionary lineages in the Chroomonas clade proved to be euryhaline. Ranges
      of osmotolerance depended not only on osmolality, but also on culture medium. All
      cryptophytes contained contractile vacuoles. In the euryhaline strain CCAP 978/08
      contractile vacuoles could be observed even at an osmolality beyond that of
      seawater. In addition the cells accumulated floridoside, an osmoprotectant likely
      originating from the red algal carbohydrate metabolism of the complex rhodoplast.
      Further evidence for functional contractile vacuoles also in marine cryptophytes
      was provided by identification of contractile vacuole-specific genes in the
      genome of Guillardia theta. 

PMID- 24568880
TI  - A registry of doctors' competing interests should include all payments by private
      hospitals.

PMID- 24568879
TI  - Innate immune recognition of respiratory syncytial virus infection.
AB  - Respiratory syncytial virus (RSV) is the leading cause of respiratory infection
      in infants and young children. Severe clinical manifestation of RSV infection is
      a bronchiolitis, which is common in infants under six months of age. Recently,
      RSV has been recognized as an important cause of respiratory infection in older
      populations with cardiovascular morbidity or immunocompromised patients. However,
      neither a vaccine nor an effective antiviral therapy is currently available.
      Moreover, the interaction between the host immune system and the RSV pathogen
      during an infection is not well understood. The innate immune system recognizes
      RSV through multiple mechanisms. The first innate immune RSV detectors are the
      pattern recognition receptors (PRRs), including toll-like receptors (TLRs),
      retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs), and nucleotide
      biding oligomerization domain (NOD)-like receptors (NLRs). The following is a
      review of studies associated with various PRRs that are responsible for RSV
      virion recognition and subsequent induction of the antiviral immune response
      during RSV infection.

PMID- 24568881
TI  - Detection of potential microbial antigens by immuno-PCR (PCR-amplified
      immunoassay).
AB  - Immuno-PCR (PCR-amplified immunoassay; I-PCR) is a novel ultrasensitive method
      combining the versatility of ELISA with the sensitivity of nucleic acid
      amplification of PCR. The enormous exponential amplification power of PCR in an I
      PCR assay leads to at least a 10(2)-10(4)-fold increase in sensitivity compared
      with an analogous ELISA. I-PCR has been used to detect many biological molecules
      such as proto-oncogenes, toxins, cytokines, hormones, and biomarkers for
      autoimmune and Alzheimer's diseases, as well as microbial antigens and
      antibodies, and it can be adapted as a novel diagnostic tool for various
      infectious and non-infectious diseases. Quantitative real-time I-PCR has the
      potential to become the most analytically sensitive method for the detection of
      proteins. The sensitivity and specificity of a real-time I-PCR assay can be
      enhanced further with the use of magnetic beads and nanoparticles. This review is
      primarily focused on the detection of potential viral, bacterial and parasitic
      antigens by I-PCR assay, thus enabling their application for immunological
      research and for early diagnosis of infectious diseases.

PMID- 24568882
TI  - A PCR-RFLP assay for the detection and differentiation of Campylobacter jejuni,
      C. coli, C. fetus, C. hyointestinalis, C. lari, C. helveticus and C. upsaliensis.
AB  - Although Campylobacter jejuni and Campylobacter coli are the most common
      bacterial causes of human gastrointestinal diseases, other Campylobacter species
      are also involved in human and animal infections. In this study, we developed a
      cytolethal distending toxin (cdt) gene-based PCR-RFLP assay for the detection and
      differentiation of C. jejuni, C. coli, C. fetus, C. hyointestinalis, C. lari, C.
      helveticus and C. upsaliensis. Previously designed common primers, which can
      amplify the cdtB gene of C. jejuni, C. coli and C. fetus, were used for detecting
      seven Campylobacter species and differentiating between them by restriction
      digestion. The PCR-RFLP assay was validated with 277 strains, including 35 C.
      jejuni, 19 C. coli, 20 C. fetus, 24 C. hyointestinalis, 13 C. lari, 2 C.
      helveticus, 22 C. upsaliensis, 3 other Campylobacter spp. and 17 other species
      associated with human diseases. Sensitivity and specificity of the PCR-RFLP assay
      were 100 % except for C. hyointestinalis (88 % sensitivity). Furthermore, the PCR
      RFLP assay successfully detected and differentiated C. jejuni, C. coli and C.
      fetus in clinical and animal samples. The results indicate that the PCR-RFLP
      assay is useful for the detection and differentiation of seven Campylobacter
      species important for human and animal diseases.

PMID- 24568884
TI  - Development of a PCR-restriction fragment length polymorphism assay for detection
      and subtyping of cholix toxin variant genes of Vibrio cholerae.
AB  - Cholix toxin (ChxA) is an exotoxin reported in Vibrio cholerae non-O1/non-O139.
      Apart from its prototype (ChxA I) we have recently identified two novel variants
      of this toxin, ChxA II and ChxA III. Our previous investigations indicated that
      the first two variants may instigate extra-intestinal infections and ChxA II can
      be more lethal than ChxA I in mice. However, all three cholix toxins (ChxA I to
      III) failed to show any enterotoxicity in rabbit ileal loops. In this study we
      developed a PCR-restriction fragment length polymorphism (RFLP) assay to
      differentiate all three chxA variants to further understand the importance of
      each subtype. By using 53 V. cholerae non-O1/non-O139 strains harbouring chxA
      genes, which were previously categorized by sequencing, and various other strains
      as negative controls, the PCR-RFLP assay showed 100 % typability and specificity.
      Furthermore, when applied to differentiate additional V. cholerae strains, which
      were also screened for the chxA gene by colony hybridization, this assay
      identified chxA I and chxA II genes among 18.5 % and 4.5 % of non-O1/non-O139
      strains (n = 178), respectively. One non-O1/non-O139 strain was untypable due to
      the insertion of an IS911-like element. Interestingly, the chxA I gene was
      detected in 10 out of 137 cholera toxin gene-negative V. cholerae O1 strains.
      These results suggest that the PCR-RFLP assay developed in this study can be a
      rapid and simple method to differentiate the chxA subtypes.

PMID- 24568883
TI  - Geographical and genospecies distribution of Borrelia burgdorferi sensu lato DNA
      detected in humans in the USA.
AB  - The present study investigated the cause of illness in human patients primarily
      in the southern USA with suspected Lyme disease based on erythema migrans-like
      skin lesions and/or symptoms consistent with early localized or late disseminated
      Lyme borreliosis. The study also included some patients from other states
      throughout the USA. Several PCR assays specific for either members of the genus
      Borrelia or only for Lyme group Borrelia spp. (Borrelia burgdorferi sensu lato),
      and DNA sequence analysis, were used to identify Borrelia spp. DNA in blood and
      skin biopsy samples from human patients. B. burgdorferi sensu lato DNA was found
      in both blood and skin biopsy samples from patients residing in the southern
      states and elsewhere in the USA, but no evidence of DNA from other Borrelia spp.
      was detected. Based on phylogenetic analysis of partial flagellin (flaB) gene
      sequences, strains that clustered separately with B. burgdorferi sensu stricto,
      Borrelia americana or Borrelia andersonii were associated with Lyme disease-like
      signs and symptoms in patients from the southern states, as well as from some
      other areas of the country. Strains most similar to B. burgdorferi sensu stricto
      and B. americana were found most commonly and appeared to be widely distributed
      among patients residing throughout the USA. The study findings suggest that human
      cases of Lyme disease in the southern USA may be more common than previously
      recognized and may also be caused by more than one species of B. burgdorferi
      sensu lato. This study provides further evidence that B. burgdorferi sensu
      stricto is not the only species associated with signs and/or symptoms consistent
      with Lyme borreliosis in the USA.

PMID- 24568885
TI  - Vaccine against tuberculosis: a view.

PMID- 24568886
TI  - The utility of FDG-PET/CT and other imaging techniques in the evaluation of IgG4
      related disease.
AB  - OBJECTIVES: This study aimed to evaluate the utility of imaging techniques,
      including 18F-fluorodeoxyglucose positron emission tomography/computed tomography
      (FDG-PET/CT), in immunoglobulin (IgG)4-related disease (IgG4-RD). METHODS: We
      reviewed eight IgG4-RD patients who were referred to our hospital between August
      2006 and April 2012. All cases underwent FDG-PET/CT and brain magnetic resonance
      imaging (MRI) and endobronchial ultrasonography (EBUS) were also performed in
      five cases and one case, respectively. RESULTS: Although nearly all patients with
      IgG4-RD in this study were negative for CRP (mean 0.22 mg/dL), various organ
      involvement sites were detected by FDG-PET/CT. In the active phase in two
      autoimmune pancreatitis (AIP) cases, FDG-PET/CT showed longitudinal and
      heterogeneous FDG accumulation in the pancreas with FDG uptake in the hilar or
      mediastinal lymph nodes. Follow-up FDG-PET/CT after therapy in one case revealed
      that the abnormal FDG uptake in all affected lesions had completely disappeared.
      In two cases, brain MRI revealed asymptomatic hypertrophic pachymeningitis. In
      one case, EBUS imaging of mediastinal lymph node swelling was consistent with
      tortuous vessels with high Doppler signals and hyperechoic strands between lymph
      nodes. CONCLUSIONS: When FDG-PET/CT shows FDG accumulation, characteristic of
      IgG4-RD in organs, without evidence of an associated inflammatory reaction, a
      diagnosis of IgG4-RD can be made. Treatment effects can be assessed by the
      disappearance of FDG uptake. A routine brain MRI is useful for detecting
      asymptomatic hypertrophic pachymeningitis. EBUS may also be useful for
      differentiating among the etiologies of lymphadenopathy with characteristic
      sonographic imaging findings.

PMID- 24568888
TI  - Metabolism and excretion of canagliflozin in mice, rats, dogs, and humans.
AB  - Canagliflozin is an oral antihyperglycemic agent used for the treatment of type 2
      diabetes mellitus. It blocks the reabsorption of glucose in the proximal renal
      tubule by inhibiting the sodium-glucose cotransporter 2. This article describes
      the in vivo biotransformation and disposition of canagliflozin after a single
      oral dose of [(14)C]canagliflozin to intact and bile duct-cannulated (BDC) mice
      and rats and to intact dogs and humans. Fecal excretion was the primary route of
      elimination of drug-derived radioactivity in both animals and humans. In BDC mice
      and rats, most radioactivity was excreted in bile. The extent of radioactivity
      excreted in urine as a percentage of the administered [(14)C]canagliflozin dose
      was 1.2%-7.6% in animals and approximately 33% in humans. The primary pathways
      contributing to the metabolic clearance of canagliflozin were oxidation in
      animals and direct glucuronidation of canagliflozin in humans. Unchanged
      canagliflozin was the major component in systemic circulation in all species. In
      human plasma, two pharmacologically inactive O-glucuronide conjugates of
      canagliflozin, M5 and M7, represented 19% and 14% of total drug-related exposure
      and were considered major human metabolites. Plasma concentrations of M5 and M7
      in mice and rats from repeated dose safety studies were lower than those in
      humans given canagliflozin at the maximum recommended dose of 300 mg. However,
      biliary metabolite profiling in rodents indicated that mouse and rat livers had
      significant exposure to M5 and M7. Pharmacologic inactivity and high water
      solubility of M5 and M7 support glucuronidation of canagliflozin as a safe
      detoxification pathway. 

PMID- 24568887
TI  - Role of ABCG2 in transport of the mammalian lignan enterolactone and its
      secretion into milk in Abcg2 knockout mice.
AB  - Lignans are phytoestrogens that are metabolized by the gut microbiota to
      enterodiol and enterolactone, the main biologically active enterolignans.
      Substantial interindividual variation in plasma concentration and urinary
      excretion of enterolignans has been reported, this being determined, at least in
      part, by the intake of lignan precursors, the gut microbiota, and the host's
      phase 2 conjugating enzyme activity. However, the role of ATP-binding cassette
      (ABC) transporters in the transport and disposition of enterolactone has not been
      reported so far. Active transport assays using parental and Madin-Darby canine
      kidney epithelial cells transduced with murine and human ABCG2 showed a
      significant increase in apically directed translocation of enterolactone in
      transduced cells, which was confirmed by using the selective ABCG2 inhibitor
      Ko143. In addition, enterolactone also inhibited transport of the antineoplastic
      agent mitoxantrone as a model substrate, with inhibition percentages of almost
      40% at 200 MUM for human ABCG2. Furthermore, the endogenous levels in plasma and
      milk of enterolactone in wild-type and Abcg2((-/-)) knockout female mice were
      analyzed. The milk/plasma ratio decreased significantly in the Abcg2((-/-))
      phenotype, as compared with the wild-type mouse group (0.4 +/- 0.1 as against 6.4
      +/- 2.6). This paper is the first to report that enterolactone is a transported
      substrate and therefore most probably a competitive inhibitor of ABCG2, which
      suggests it has a role in the interindividual variations in the disposition of
      enterolactone and its secretion into milk. The inhibitory activity identified
      provides a solid basis for further investigation in possible food-drug
      interactions. 

PMID- 24568889
TI  - Efficacy of topical ALA-PDT combined with excision in the treatment of skin
      malignant tumor.
AB  - BACKGROUND: Photodynamic therapy (PDT) is a successful treatment for non-melanoma
      skin cancers in clinical practice. In China, more and more doctors use PDT to
      cure the patients with skin cancer, especially in the elder. The purpose of this
      study was to evaluate the efficacy of topical PDT using aminolevulinic acid (5
      ALA) combined with excision in the treatment of skin malignant tumor and its role
      in surgical improvements. METHODS: A total of 58 cases including 32 cases of BCC,
      13 cases of Bowen's disease, 8 cases of Paget's disease and 5 cases of SCC were
      included in this study. All cases were treated with topical ALA-PDT after
      surgery. Each tumor region was irradiated with 120 J/cm(2) using a 635-nm laser
      for 15 min. A total of 3 times of assisted ALA-PDT was applied after surgery.
      RESULTS: There was no recurrence in 6 months after treatment. Only 5 cases of
      Paget's disease and 2 cases of SCC experienced disease recurrence in 1 year. All
      patients were able to complete the treatment protocol, with well cosmetic results
      and no moderate adverse reactions. CONCLUSIONS: As an assistive therapy after
      tumor resection, ALA-PDT can reduce the excision range of the tumor lesions.
      However, its role in the reduction of recurrence rate remains to be further
      investigated.

PMID- 24568890
TI  - Comparison of 5-aminolevulinic acid photodynamic therapy and red light for
      treatment of photoaging.
AB  - OBJECTIVE: The aim of this pilot study was to compare the efficacy of ALA-PDT and
      red light alone in the treatment of photoaging. METHODS: A total of 14 adults
      with photoaging skin were recruited. ALA-PDT or red light alone was applied to
      the forearm extensor. Before and after treatment, the treated sites were examined
      by dermoscopy, the changes in straum corneum (SC) hydration, transepidermal water
      loss (TEWL), and the L*a*b* values were measured, and microscopic examination of
      collagens and elastins was performed. RESULTS: After ALA-PDT or red light
      illumination, the appearance of photoaging lesions improved, SC hydration
      increased and TEWL decreased. These changes in the ALA-PDT group were more
      obvious than those in the red light group. No significant change was noticed in
      the L*a*b* values in both groups. The signs of typical solar elastosis damage
      were improved in both groups. CONCLUSIONS: ALA-PDT showed better skin
      rejuvenation effect than red light alone.

PMID- 24568891
TI  - Pharmacokinetics of an anti-TFPI monoclonal antibody (concizumab) blocking the
      TFPI interaction with the active site of FXa in Cynomolgus monkeys after iv and
      sc administration.
AB  - INTRODUCTION: Concizumab (mAb 2021) is a monoclonal IgG4 antibody (mAb) that
      binds to the Kunitz-type protease inhibitor (KPI) 2 domain of TFPI thereby
      blocking the interaction of this domain with the active site of FXa. The
      objective of the present study was to characterize the pharmacokinetics of
      concizumab in Cynomolgus monkeys after intravenous (iv) and subcutaneous (sc)
      administration. METHODS: Data from two studies were included in the modelling,
      all in all data from 52 monkeys distributed into 9 groups. Three groups received
      three escalating sc doses of concizumab with a one week dosing interval, two
      groups were administered a single dose, and four groups received multiple doses
      over 13 weeks of concizumab. The plasma concentration was measured using a
      standard ELISA, and pharmacokinetic data were analysed using NONMEM. RESULTS: The
      pharmacokinetics of concizumab were characterised by a high bioavailability (93%)
      after sc administration. The time course of the elimination of concizumab from
      the circulation was well described by the proposed target mediated drug
      disposition (TMDD) model. The clearance of concizumab was estimated to be 0.14
      ml/h/kg, the target clearance was characterized by a 50% saturation level of 0.54
      MUg/ml (Km), and the clearance at target saturation was estimated to be 11
      MUg/h/kg. CONCLUSION: Concizumab displays a typical TMDD profile with important
      implications for a putative treatment regime in haemophilia patients. Compared to
      current standard haemophilia treatment, concizumab has a high bioavailability
      after sc administration and may provide a viable alternative to intravenous
      dosing for the treatment of haemophilia.

PMID- 24568892
TI  - Hospital website rankings in the United States: expanding benchmarks and
      standards for effective consumer engagement.
AB  - BACKGROUND: Passage of the Patient Protection and Affordable Care Act (ACA)
      increased the roles hospitals and health systems play in care delivery and led to
      a wave of consolidation of medical groups and hospitals. As such, the traditional
      patient interaction with an independent medical provider is becoming far less
      common, replaced by frequent interactions with integrated medical groups and
      health systems. It is thus increasingly important for these organizations to have
      an effective social media presence. Moreover, in the age of the informed
      consumer, patients desire a readily accessible, electronic interface to initiate
      contact, making a well-designed website and social media strategy critical
      features of the modern health care organization. OBJECTIVE: The purpose of this
      study was to assess the Web presence of hospitals and their health systems on
      five dimensions: accessibility, content, marketing, technology, and usability. In
      addition, an overall ranking was calculated to identify the top 100 hospital and
      health system websites. METHODS: A total of 2407 unique Web domains covering 2785
      hospital facilities or their parent organizations were identified and matched
      against the 2009 American Hospital Association (AHA) Annual Survey. This is a
      four-fold improvement in prior research and represents what the authors believe
      to be a census assessment of the online presence of US hospitals and their health
      systems. Each of the five dimensions was investigated with an automated content
      analysis using a suite of tools. Scores on the dimensions are reported on a range
      from 0 to 10, with a higher score on any given dimension representing better
      comparative performance. Rankings on each dimension and an average ranking are
      provided for the top 100 hospitals. RESULTS: The mean score on the usability
      dimension, meant to rate overall website quality, was 5.16 (SD 1.43), with the
      highest score of 8 shared by only 5 hospitals. Mean scores on other dimensions
      were between 4.43 (SD 2.19) and 6.49 (SD 0.96). Based on these scores, rank order
      calculations for the top 100 websites are presented. Additionally, a link to raw
      data, including AHA ID, is provided to enable researchers and practitioners the
      ability to further explore relationships to other dynamics in health care.
      CONCLUSIONS: This census assessment of US hospitals and their health systems
      provides a clear indication of the state of the sector. While stakeholder
      engagement is core to most discussions of the role that hospitals must play in
      relation to communities, management of an online presence has not been recognized
      as a core competency fundamental to care delivery. Yet, social media management
      and network engagement are skills that exist at the confluence of marketing and
      technical prowess. This paper presents performance guidelines evaluated against
      best-demonstrated practice or independent standards to facilitate improvement of
      the sector's use of websites and social media.

PMID- 24568893
TI  - Are we satisfied? Perspective on five-year outcomes of midurethral slings.

PMID- 24568894
TI  - Alcohol intake increases high-grade prostate cancer risk among men taking
      dutasteride in the REDUCE trial.
AB  - BACKGROUND: Although most studies found no association between alcohol intake and
      prostate cancer (PCa) risk, an analysis of the Prostate Cancer Prevention Trial
      found that high alcohol intake significantly increased PCa risk among men
      randomized to the 5alpha-reductase inhibitor (5-ARI) finasteride. OBJECTIVE:
      Determine whether alcohol affects PCa risk among men taking the 5-ARI
      dutasteride. DESIGN, SETTINGS, AND PARTICIPANTS: Reduction by Dutasteride of
      Prostate Cancer Events was a 4-yr, multicenter, randomized, double-blind, placebo
      controlled trial to compare PCa after dutasteride administration (0.5mg/d) with
      placebo. Participants had a baseline prostate-specific antigen between 2.5 and
      10.0 ng/ml and a recent negative prostate biopsy. Alcohol intake was determined
      by baseline questionnaire, and participants underwent a prostate biopsy to
      determine PCa status at 2 yr and 4 yr of follow-up. OUTCOME MEASUREMENTS AND
      STATISTICAL ANALYSIS: Multivariable logistic regression was used to calculate
      odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between
      alcohol intake and low-grade (Gleason <7) and high-grade (Gleason >7) PCa.
      RESULTS AND LIMITATIONS: Of 6374 participants in our analysis, approximately 25%
      reported no alcohol consumption, 49% were moderate drinkers (one to seven drinks
      per week), and 26% were heavy drinkers (more than seven drinks per week). Alcohol
      intake was not associated with low- or high-grade PCa in the placebo arm and was
      not associated with low-grade PCa among men taking dutasteride. In contrast, men
      randomized to dutasteride and reporting more than seven drinks per week were 86%
      more likely to be diagnosed with high-grade PCa (p=0.01). Among alcohol
      abstainers, dutasteride was associated with significantly reduced risk of high
      grade PCa (OR: 0.59; 95% CI, 0.38-0.90), but dutasteride was no longer associated
      with reduced high-grade PCa among men reporting high alcohol intake (OR: 0.99;
      95% CI, 0.67-1.45). CONCLUSIONS: Alcohol consumption negated a protective
      association between dutasteride and high-grade PCa. PATIENT SUMMARY: We confirmed
      a prior study that alcohol affects PCa prevention in patients taking 5-ARIs.
      Patients taking 5-ARIs may wish to eliminate alcohol intake if they are concerned
      about PCa.

PMID- 24568895
TI  - Reply from authors re: Cora N. Sternberg, Richard Sylvester. Thoughts on a
      systematic review and meta-analysis of adjuvant chemotherapy in muscle-invasive
      bladder cancer. Eur Urol 2014;66:55-6.

PMID- 24568896
TI  - Dissecting the association between metabolic syndrome and prostate cancer risk:
      analysis of a large clinical cohort.
AB  - BACKGROUND: A biologic rationale exists for the association between metabolic
      syndrome (MetS) and prostate cancer (PCa). However, epidemiologic studies have
      been conflicting. OBJECTIVE: To evaluate the association between MetS and the
      odds of PCa diagnosis in men referred for biopsy. DESIGN, SETTING, AND
      PARTICIPANTS: Patients without prior PCa diagnosis undergoing prostate biopsy
      were identified from a large prostate biopsy cohort (in Toronto, Canada). The
      definition of MetS was based on the most recent interim joint consensus
      definition, requiring any three of five components (obesity, elevated blood
      pressure, diabetes or impaired fasting glucose, low high-density lipoprotein
      cholesterol, and hypertriglyceridemia). Both the individual components of MetS
      and the cumulative number of MetS components were evaluated. OUTCOME MEASUREMENTS
      AND STATISTICAL ANALYSIS: The outcomes were PCa detection overall, clinically
      significant PCa (CSPC; defined as any Gleason pattern >= 4, >50% involvement of a
      single biopsy core, or more than one of three total number of cores involved),
      and intermediate- or high-grade PCa (I-HGPC; Gleason 7-10). Tests for trend and
      multivariable logistic regression analyses were performed. RESULTS AND
      LIMITATIONS: Of 2235 patients, 494 (22.1%) had MetS. No individual MetS component
      was independently associated with PCa. However, increasing number of MetS
      components was associated with higher PCa grade (p<0.001), as well as
      progressively higher odds of PCa outcomes (three or more; ie, MetS) compared with
      no MetS components: Odds ratios were 1.54 for PCa overall (95% confidence
      interval [CI], 1.17-2.04; p=0.002), 1.56 for CSPC (95% CI, 1.17-2.08; p=0.002),
      and 1.56 for I-HGPC (95% CI, 1.16-2.10; p=0.003) in multivariable analyses. The
      main limitation is the retrospective design. CONCLUSIONS: Although the individual
      MetS components are not independently associated with PCa outcomes, MetS is
      significantly associated with higher odds of PCa diagnosis, CSPC, and I-HGPC.
      There is a biologic gradient between the number of MetS components and the risk
      of PCa, as well as cancer grade. PATIENT SUMMARY: Metabolic syndrome is a
      collection of metabolic abnormalities that increases one's risk for heart
      disease. Our study shows that an increasing degree of metabolic abnormality is
      also associated with an increased risk of diagnosis of overall and aggressive
      prostate cancer.

PMID- 24568898
TI  - [A review on treatment of high-risk neuroblastoma].
AB  - So far treatment of advanced neuroblastoma is still difficult, due to its high
      malignancy. Currently comprehensive therapies, including high-dose multi-drug
      chemotherapy, surgery, stem cell transplantation, radiation, biological therapy
      and immune therapy as well as target therapy dominant the treatment of this
      disease, and we hereby introduce the latest development of treatment protocols
      for this disease. 

PMID- 24568899
TI  - [Strategies to improve therapeutic efficacy in childhood acute myeloid leukemia].
AB  - Acute myeloid leukemia (AML) is a rare type of childhood acute leukemia, which
      has a worse prognosis than childhood acute lymphoblastic leukemia. Over the past
      decade, significant progress has been made in the treatment of childhood AML and
      the 5-year event-free survival rate may be as high as 70% in developed countries.
      This survival improvement is largely attributable to risk-stratified treatments,
      therapies tailored to individual patients based on the biological characteristics
      of the disease, and continuously improving supportive care. An accurate diagnosis
      is the prerequisite for risk stratification, prognostic evaluation and
      therapeutic decision making. How to reduce early mortality and thus improve
      overall survival, how to implement appropriate supportive treatment to reduce
      treatment-associated complications, and how to reduce treatment-related mortality
      are the key to the improvement of therapies for childhood acute myeloid leukemia.

PMID- 24568897
TI  - Diurnal patterns and associations among salivary cortisol, DHEA and alpha-amylase
      in older adults.
AB  - BACKGROUND: Cortisol and dehydroepiandrosterone (DHEA) are considered to be
      valuable markers of the hypothalamus-pituitary-adrenal (HPA) axis, while salivary
      alpha-amylase (sAA) reflects the autonomic nervous system. Past studies have
      found certain diurnal patterns among these biomarkers, with some studies
      reporting results that differ from others. Also, some past studies have found an
      association among these three biomarkers while other studies have not. This study
      investigates these patterns and associations in older adults by taking advantage
      of modern statistical methods for dealing with non-normality, outliers and
      curvature. Basic characteristics of the data are reported as well, which are
      relevant to understanding the nature of any patterns and associations. METHODS:
      Boxplots were used to check on the skewness and presence of outliers, including
      the impact of using simple transformations for dealing with non-normality.
      Diurnal patterns were investigated using recent advances aimed at comparing
      medians. When studying associations, the initial step was to check for curvature
      using a non-parametric regression estimator. Based on the resulting fit, a robust
      regression estimator was used that is designed to deal with skewed distributions
      and outliers. RESULTS: Boxplots indicated highly skewed distributions with
      outliers. Simple transformations (such as taking logs) did not deal with this
      issue in an effective manner. Consequently, diurnal patterns were investigated
      using medians and found to be consistent with some previous studies but not
      others. A positive association between awakening cortisol levels and DHEA was
      found when DHEA is relatively low; otherwise no association was found. The nature
      of the association between cortisol and DHEA was found to change during the
      course of the day. Upon awakening, cortisol was found to have no association with
      sAA when DHEA levels are relatively low, but otherwise there is a negative
      association. DHEA was found to have a positive association with sAA upon
      awakening. Shortly after awakening and for the remainder of the day, no
      association was found between DHEA and sAA ignoring cortisol. For DHEA and
      cortisol (taken as the independent variables) versus sAA (the dependent
      variable), again an association is found only upon awakening.

PMID- 24568900
TI  - [Treatment of endodermal sinus tumor in children].
AB  - OBJECTIVE: To study the treatment and outcome of childhood endodermal sinus
      tumor. METHODS: The clinical data of twelve children with endodermal sinus tumor
      between April 2000 and July 2013 were reviewed. The basic demographics, stages of
      the lesion and the treatment outcome were analyzed. Of the twelve patients, seven
      were boys and five were girls. The age of the disease onset was between 1 and 3.3
      years, except one in 11 years. Two patients were in Brodeur Stage I, four in
      Stage II, two in Stage III, and four in Stage IV. One patient underwent surgery
      alone, one underwent surgery plus a combination therapy with vincristine,
      actinomycin and cyclophosphamide (VAC), and the other ten were treated by surgery
      with the use of cisplatin, etoposide and bleomycin (PEB) before or after the
      operation. RESULTS: Eleven patients were successfully followed up and ten were
      alive. The length of survival was 4.5 to 66 months in the 10 patients. In the 10
      patients treated with PEB before or after surgery, 8 achieved complete remission,
      one achieved partial remission and one was not followed up. The major
      complications associated with the PEB regimen included myelosuppression and
      gastrointestinal upset symptoms and no late toxicity was observed. CONCLUSIONS:
      Preoperative or postoperative administration of PEB may be an effective and safe
      management modality for childhood endodermal sinus tumor. Nevertheless, further
      validation is warranted in prospective studies involving a larger sample size.

PMID- 24568901
TI  - [Effect of matrine and cisplatin in combination on PDCD4 expression in SK-NEP-1
      cells].
AB  - OBJECTIVE: Matrine, a major ingredient of sophora, has an anti-tumor activity,
      capable of suppressing the proliferation and metastasis and promoting apoptosis
      or differentiation of tumor cells. This study was designed to investigate the
      effects of matrine on survival and apoptosis of nephroblastoma cell line SK-NEP
      1, reduction of drug-resistance of cisplatin and the mechanism(s) underlying
      these effects. METHODS: SK-NEP-1 cells were treated with matrine and cisplatin at
      various doses (0.5, 1.0 and 1.5 mg/mL), either each alone or in combination. The
      viability in treated SK-NEP-1 cells was assessed by MTT colorimetric assay,
      apoptosis by flow cytometry, and PDCD4 mRNA abundance by RT-PCR. RESULTS: As
      compared with the non-treatment control, matrine and cisplation, regardless of
      combination and dosage, significantly reduced the viability (P<0.01), induced
      apoptosis (P<0.01), and increased PDCD4 mRNA abundance (P<0.01), in SK-NEP-1
      cells. The above effects of matrine and cisplation were dose-dependent when they
      were used alone, and were more pronounced when they were used in combination
      (P<0.05). CONCLUSIONS: Matrine can significantly induce apoptosis and inhibit
      growth of SK-NEP-1 cells in a dose-dependent manner, thus increasing the
      chemotherapeutic sensibility of cisplatin. The observed effects of matrine may be
      a result of increased PDCD4 expression.

PMID- 24568902
TI  - [Management of refractory neuroblastoma with high-dose topotecan plus
      cyclophosphamide and vincristine].

PMID- 24568903
TI  - [Treatment of advanced malignant solid tumor by autologous peripheral blood stem
      cell transplantation in children: experience of 38 cases].

PMID- 24568904
TI  - [Clinical and biological characteristics of childhood acute myeloid leukemia with
      EVI1 gene positive expression].
AB  - OBJECTIVE: To study the expression of ecotropic viral integration site (EVI1)
      gene in childhood acute myeloid leukemia (AML) and the clinical features of EVI1
      positive children with AML. METHODS: The clinical data of EVI1-positive children
      with AML were collected and analyzed. RT-PCR and real-time quantitative PCR were
      used for qualitative and quantitative analysis of expression of EVI1. Flow
      cytometry (FCM) was used for determining the immunophenotypes of bone marrow
      cells. Multiparameter FCM was used for monitoring minimal residual disease. The
      karyotypes were determined. RESULTS: Of 241 children with AML, 33 (13.7%) were
      positive for EVI1 expression. There were no significant differences in age at
      first visit as well as the white blood cell count, hemoglobin level, and platelet
      count in peripheral blood between EVI1-positive and EVI1-negative children with
      AML (P>0.05), but EVI1-positive children had a significantly increased proportion
      of females compared with EVI1-negative children (P<0.05). The change in EVI1
      expression was not synchronous with clinical remission and the change of MRD:
      some children had clinical remission or negative conversion of MRD before
      negative conversion of EVI1, while some had negative conversion of EVI1 before
      clinical remission or while MRD showed positive. EVI1 gene was usually co
      expressed with other fusion genes. CD33 (100%), CD38 (88%), and HLADR (76%) were
      highly expressed in EVI1-positive children with AML. Abnormal chromosome
      structure or number was found in 15 patients. Compared with EVI1-negative
      children, EVI1-positive children had significantly lower complete remission rates
      after the first course of treatment (P<0.05). CONCLUSIONS: EVI1-positive children
      with AML have a poor short-term prognosis. In the development of AML, the
      activation of EVI1 gene is not isolated, but the result of interactions with
      other genes or chromosome abnormalities, and the mechanism of activation and its
      function need further study.

PMID- 24568905
TI  - [Effect of Apollon siRNA combined with tetramethylpyrazine on proliferation and
      apoptosis of leukemia K562 cells].
AB  - OBJECTIVE: To investigate the effect of small interfering RNA (siRNA) silencing
      Apollon gene combined with tetramethylpyrazine (TMP) on the proliferation and
      apoptosis of human chronic myeloid leukemia cell line K562. METHODS: K562 cells
      were divided into blank control, negative control, and RNA interference (RNAi)
      group. For the RNAi group, the pGPHI-GFP-Neo-Apollon eukaryotic expression vector
      based on the best Apollon siRNA fragments screened out in previous experiments
      was constructed; the blank control group received no treatment, and the negative
      control group was transfected with negative plasmid vector. The mRNA and protein
      expression of Apollon was measured by RT-PCR and cell immunofluorescence,
      respectively. Additionally, TMP (320 MUg/mL) was applied to set TMP, TMP+negative
      control, and TMP+RNAi groups. The cell viability and apoptosis rate were
      determined by MTT assay and flow cytometry, respectively. RESULTS: The
      constructed vector was stably expressed in K562 cells. The RNAi group had
      significantly lower mRNA and protein expression of Apollon than the blank control
      group and negative control (P<0.05). The RNAi group had significantly increased
      proliferation inhibition rate and apoptosis rate, as compared with the blank
      contorl group (P<0.05). The TMP+RNAi group had significantly increased
      proliferation inhibition rate and apoptosis rate, as compared with the RNAi, and
      TMP groups (P<0.05). CONCLUSIONS: Apollon siRNA can significantly inhibit the
      proliferation and promote the apoptosis of K562 cells, and the addition of TMP
      can further increase the proliferation inhibition rate and apoptosis rate,
      suggesting that siRNA technology combined with drugs has a significant potential
      value in the treatment of leukemia.

PMID- 24568906
TI  - [Effect of Huangqi injection on short-term prognosis in children with acute
      lymphoblastic leukemia].
AB  - OBJECTIVE: To investigate the effect of Huangqi injection on the short-term
      prognosis in childhood with acute lymphoblastic leukemia (ALL). METHODS: A
      retrospective analysis was performed on the clinical data of 105 children newly
      diagnosed with ALL between January 2009 and December 2012. These children were
      randomly divided into treatment group (18 low-risk cases, 7 medium-risk cases,
      and 24 high-risk cases) and control group (21 low-risk cases, 7 medium-risk
      cases, 28 high-risk cases). Both groups were given remission induction therapy
      based on the levels of risk. Throughout the remission induction therapy, the
      treatment group also received Huangqi injection (0.5-1.0 mL/kg per day) by
      intravenous infusion, while the control group was given 0.9% sodium chloride
      injection instead. The two groups were compared in terms of distribution of
      prognostic factors and complete remission (CR) rate after remission induction
      therapy, as well as the incidence of minimal residual disease (MDR) (>= 10(-4)
      and < 10(-4)) among all patients in the two groups on day 19 of remission
      induction therapy and among B-ALL patients in the two groups when achieving a CR
      at the end of remission induction therapy. RESULTS: Of the 105 children with ALL,
      99 had B-ALL, and 6 had T-ALL. There were no significant differences in the
      distribution of prognostic factors between the two groups (P>0.05). The overall
      CR rate of 105 patients was 79%; there was no significant difference in CR rate
      between the treatment and control groups (82% vs 77%; P>0.05); also, no
      significant differences were found between the two groups in the CR rates among
      high-, medium-, and low-risk cases (P>0.05). On day 19 of remission induction
      therapy, the incidence of MRD>=10(-4) in the treatment group was significantly
      lower than that in the control group (69% vs 95%; P<0.05); among 80 children with
      B-ALL who achieved a CR (43 cases in the control group and 37 cases in the
      treatment group), the incidence of MRD>=10-4 was significantly lower in the
      treatment group than in the control group (27% vs 58%; P<0.05); in both
      circumstances above, the high- and low-risk cases in the treatment group had a
      significantly lower incidence of MRD>=10(-4) than the control group (P<0.05).
      CONCLUSIONS: Huangqi injection combined with chemotherapy has an enhanced anti
      tumor effect and can improve the short-term prognosis and clinical outcome in
      children with ALL.

PMID- 24568907
TI  - [Effects of Huangqi injection on infection factors in children with acute
      lymphoblastic leukemia].
AB  - OBJECTIVE: To investigate the effects of Huangqi injection on the infection
      factors in children with acute lymphoblastic leukemia (ALL) during remission
      induction chemotherapy. METHODS: Ninety-one children with ALL were divided into
      treatment (n=47) and control groups (n=44) by a randomized double-blind method.
      During remission induction chemotherapy, the treatment group was given Huangqi
      injection (0.5 mL/kg.d) for 35 days, while an equal volume of normal saline was
      used instead in the control group; the other supportive care was the same for the
      two groups. After remission induction chemotherapy, the incidence of infection,
      duration of infection, white blood cell and neutrophil counts, site of infection,
      and positive rate of pathogenic bacteria in secretion were compared between the
      two groups. RESULTS: Four cases in the treatment group dropped out of the study
      due to allergic reaction. After remission induction chemotherapy, compared with
      the control group, the treatment group had a significantly lower incidence of
      infection (P<0.05), a shorter duration of infection at any site (P<0.05), a
      higher neutrophil count after chemotherapy (P<0.05), and lower incidence rates of
      respiratory tract infection, urinary tract infection, blood infection, and skin
      and soft tissue infections (P<0.05). Gram-negative bacteria were the main
      pathogens. Among the infected children, the positive rate of pathogenic bacteria
      in secretion was significantly lower in the treatment group than in the control
      group (P<0.05). CONCLUSIONS: Huangqi injection may reduce bone marrow suppression
      caused by chemotherapy drugs and increase neutrophil count during remission
      induction chemotherapy to reduce the incidence and duration of infection in
      children with ALL.

PMID- 24568908
TI  - [Concurrent mucormycosis in children with acute lymphoblastic leukemia at induced
      remission stage: two case report].

PMID- 24568909
TI  - [Advances on the role of pegaspargase in the treatment of childhood leukemia].
AB  - The chemotherapy agent L-asparaginase (L-asp) has been an important part of acute
      lymphoblastic leukemia therapy for over 30 years. It is evident that L-asp has a
      long-term curative effect. However, L-asp is associated with high incidence of
      adverse reactions. This has prompted the development of pegylated asparaginase
      (PEG-asp), which has undergone extensive testing. Apparently, PEG-asp has a
      prolonged half-life with a better tolerance profile while retaining the
      antileukemic effect. In this review, we attempt to outline the history of
      clinical application of L-asp, the pharmacological and clinical potential of
      various preparations of L-asp, the development of PEG-asp, and the clinical
      application and adverse events of PEG-asp. The literatures reviewed in this
      article is collected through online search of the major databases both in English
      and Chinese. 

PMID- 24568910
TI  - [Significance of exhaled nitric oxide measurement in remitting childhood asthma
      with concurrent remitting rhinitis].
AB  - OBJECTIVE: To evaluate the value of exhaled nitric oxide in the severity
      evaluation of asthmatic children with remitting rhinitis. METHODS: A total of 214
      asthmatic children were randomly allocated to a untreated control and a
      conventional treatment group. Patients in each of the two subclasses were
      classified as asthma with concurrent rhinitis and asthma without concurrent
      rhinitis. Values of the 20% fall in forced expiratory volume in 1 second
      (PC20FEV1) and fractional exhaled nitric oxide (FeNO) were measured. RESULTS: The
      PC20FEV1 level was significantly higher in untreated asthma patients without
      rhinitis than in those with concurrent rhinitis (P<0.05), while FeNO was not
      significantly different between these two groups (P>0.05). There were no
      significant differences in both FeNO and PC20FEV1 between treated asthma patients
      with and without concurrent rhinitis (P>0.05). PC20FEV1 was significantly
      increased (P<0.05) but FeNO was significantly decreased (P<0.05) in asthma
      patients with concurrent rhinitis after conventional treatment. In asthmatic
      children without concurrent rhinitis, treatment significantly decreased the level
      of FeNO (P<0.05) but had not effect on PC20FEV1 (P>0.05). CONCLUSIONS: Exhaled
      nitric oxide measurement may be useful in the severity evaluation of asthmatic
      children with remitting rhinitis.

PMID- 24568912
TI  - [Application of combined esophageal multichannel intraluminal impedance-pH
      monitoring in infants and children with gastroesophageal reflux disease].
AB  - OBJECTIVE: This study aimed to evaluate the diagnostic value of a 24-hour
      esophageal combined multichannel intraluminal impedance pH (24 h our MII-pH)
      monitoring in children with gastroesophageal reflux (GER) disease and recurrent
      pneumonia. METHODS: A total of 17 cases with a suspected diagnosis of GER disease
      children with unexplained recurrent pneumonia underwent a 24-hour MII-pH
      monitoring to analysis of the nature and characteristics of reflux. RESULTS: In
      the 17 cases of GER disease with recurrent pneumonia, 11 (65%) were confirmed
      positively by a 24-hours of MII-pH monitoring. A total of 853 reflux cycle were
      detected, of which 65.3% were acid refluxes predominantly occurring within 2
      hours after meal, and 71.6% were mixed refluxes. Refluxes occurred most
      frequently in the supine position, followed by the lateral position and the prone
      position. Distal reflux was the predominant form of reflux. According to the Biox
      Ochoa classification, 73% of cases (8/11) were severe GER. CONCLUSIONS: MII-pH
      monitoring may effectively characterize refluxate properties and thereby increase
      the detection rate of GER disease.

PMID- 24568911
TI  - [Epidemiological survey of childhood asthma in 2010 in urban Baotou, China].
AB  - OBJECTIVE: To investigate the prevalence rate of childhood asthma in 2010 in
      urban Baotou, China, as well as the characteristics of attacks and the status of
      diagnosis and treatment of childhood asthma. METHODS: More than 10 000 children
      (0-14 years) were selected from 3 secondary schools, 3 primary schools, 6
      kindergartens, and 4 community vaccination sites in urban Baotou by cluster
      random sampling between September 2009 and August 2010. A standardized
      preliminary questionnaire was used for screening out suspected cases, which were
      then confirmed or excluded by a clinician; the confirmed cases underwent further
      questionnaire survey. Double entry and validation was adopted for all data using
      Epi-Info software, and analysis was performed using SPSS 13.0. RESULTS: A total
      of 11 323 children were surveyed. Asthma was diagnosed in 127 cases (including
      121 children with typical asthma and 6 children with cough variant asthma), with
      a prevalence rate of 1.12%. The prevalence rate of asthma in male children was
      significantly higher than that in female children (1.51% vs 0.72%; P<0.01). The
      prevalence rate of asthma in 2010 was significantly increased compared with that
      in 1990 (0.55%) and 2000 (0.88%) (P<0.05). Systemic glucocorticoid use decreased
      significantly from 60.2% in 2000 to 25.9% in 2010 (P<0.01); inhaled
      corticosteroid use increased significantly from 13.6% in 2000 to 85.8% in 2010
      (P<0.01); antibiotic use decreased from 98.1% in 2000 to 66.9% in 2010 (P<0.01).
      The multivariate logistic regression analysis showed that family history of
      allergy, allergic rhinitis, chronic cough, and recurrent respiratory tract
      infection were independent risk factors for childhood asthma. CONCLUSIONS: The
      prevalence rate of childhood asthma in urban Baotou shows an increasing trend.
      Inhaled corticosteroids have been widely used.

PMID- 24568913
TI  - [A splicing mutation of EXT1 in a Chinese pedigree with hereditary multiple
      exostoses].
AB  - OBJECTIVE: Hereditary multiple exostoses (HME) is an autosomal dominant monogenic
      disorder of paraplasia ossium. Mutations in EXT1 and EXT2 have been suggested to
      be responsible for over 70% of HME cases. This study aimed to analyze the
      clinical features and pathogenic mutations in a Chinese family with HME (6
      patients in 24 members of 3 generations) and to review the relative literature
      regarding mutations in EXT1 and EXT2 in the Chinese population. METHODS: Clinical
      pedigree dada from a Chinese family of HME were collected and analysed. EXT gene
      mutations in this pedigree assessed by PCR and sequencing. Pubmed and Wanfang (a
      Chinese database) were searched for the literature related to gene mutations in
      Chinese HME patients. RESULTS: In the pedigree analyzed, the age of onset of HME
      was becoming younger, the disease was becoming more severe, and the number of
      osteochondromas was increasing, in successive generations. A splicing mutation
      IVS5+1G>A, first identified in Chinese population, was found in all diseased
      members of this pedigree. According the currently available literature, EXT1 and
      EXT2 mutations have been detected in 29% (26/90) and 43% (39/90) Chinese families
      with HME. CONCLUSIONS: HME starts earlier and becomes more severe and extensive
      with each successive generation in members of the pedigree analyzed. A splicing
      mutation, IVS5+1G>A, of EXT1, first identified in Chinese population, may be
      responsible for HME in the studied pedigree. EXT1 and EXT2 mutation rates may be
      different between the Chinese and Western populations.

PMID- 24568914
TI  - [Association of IL-1beta-511T gene rs16944 polymorphism with febrile seizures].
AB  - OBJECTIVE: Despite substantial research efforts worldwide, the role of
      inflammatory cytokine IL-1beta in the onset of febrile seizures (FS) remains
      controversial. The aim of this study was to assess the relationship between
      rs16944 polymorphism of the IL-1beta-511T gene and occurrence of simple FS in a
      sample of Han children in northern China. METHODS: The IL-1beta-511T gene rs16944
      was genotyped by SNaPshot SNP technique in 141 FS children and 130 healthy
      control subjects. The genotypic and allelic frequencies in the two groups were
      comparatively analyzed. RESULTS: There were no significant differences in
      genotypic and allelic frequencies of rs16944 polymorphism of the IL-1beta-511T
      gene between FS patients and control subjects (P>0.05).When the clinical data on
      A/A, A/G and G/G genotypes of the rs16944 polymorphism in FS patients, there was
      statistically significant difference in age of first onset (chi(2)=19.491,
      P<0.01), temperature of first onset (chi(2)=9.317, P<0.05) and family history of
      FS (chi(2)=26.798, P<0.01). CONCLUSIONS: There is no association between rs16944
      polymorphism of the IL-1beta-511T gene and the incidence of FS in Han children in
      Northern China. However, the differences in genotypes of this polymorphism might
      be associated with pathogenesis and prognosis of simple FS in the population
      studied.

PMID- 24568915
TI  - [Effect of parent training in combination with methylphenidate treatment on
      family relationships for children with attention deficit/hyperactivity disorder].
AB  - OBJECTIVE: To investigate the effect of parent training combined with
      methylphenidate treatment on family relationships in children with attention
      deficit/hyperactivity disorder (ADHD). METHODS: Fifty-nine parents of children
      with ADHD under methylphenidate treatment participated in a modified 5-week
      training program. The intervention effect was evaluated using the Conners Parent
      Symptom Questionnaire, ADHD Rating Scale-IV Home Version (ADHD-RS-IV Home
      Version), Caregiver Strain Questionnaire, Parent-Child Relationship Self-rating
      Scale and Piers-Harris Children's Self-Concept Scale. Parents also completed the
      training satisfaction survey before and after the intervention. RESULTS: After
      the 5-week parent training, compared with the baseline values, total scores of
      Conners Parent Symptom Questionnaire and scores of conduct problems and anxiety
      significantly decreased, and scores of attention deficit, hyperactivity,
      impulsivity and oppositional defiant behaviors of ADHD-RS-IV Home Version, and
      Caregiver Strain Questionnaire total scores were all significantly decreased
      (P<0.05), while total scores of the Parent-Child Relationship Self-Rating Scale
      and Piers-Harris Children's Self-Concept Scale were significantly increased
      (P<0.05). CONCLUSIONS: Modified 5-week parent training program may improve parent
      child relationship and reduce parenting stress in ADHD families.

PMID- 24568916
TI  - [Prognostic values of serum procalcitonin level and pediatric critical illness
      score in children with sepsis].
AB  - OBJECTIVE: To investigate the correlation between serum procalcitonin (PCT) level
      and pediatric critical illness score (PCIS) and their prognostic values in
      children with sepsis. METHODS: Sixty-one children with sepsis in the pediatric
      intensive care unit were enrolled. According to PCIS, these patients were divided
      into non-critical (n=18), critical (n=20), and extremely critical groups (n=23).
      Within 24 hours after admission, serum levels of PCT, C-reactive protein (CRP),
      and lactic acid (LA) and routine blood counts were measured. These parameters
      were compared between the three groups. The Pearson correlation analysis was
      performed to determine the correlation of PCT with PCIS and other serological
      parameters. Based on clinical outcomes, these patients were divided into survival
      (n=39) and death groups (n=22). The PCT, PCIS, and other serological parameters
      were compared between the two groups. RESULTS: The serum levels of PCT and CRP in
      the non-critical group were significantly lower than those in critical group and
      extremely critical groups (P<0.05), and the two parameters were significantly
      lower in the critical group than in the extremely critical groups (P<0.05). The
      extremely critical group had a significantly higher mortality than the critical
      group non-critical groups (61% vs 35% and 6%, P<0.05). Serum PCT level had a
      significantly negative correlation with PCIS (r=-0.63, P<0.001) but a
      significantly positive correlation with serum CRP level (r=0.73, P=0.003).
      Compared with the death group, the survival group had significantly higher serum
      levels of PCT and LA (P<0.05) but a significantly lower PCIS (P<0.05).
      CONCLUSIONS: There is a good correlation between serum PCT level and PCIS. For
      children with sepsis, the lower the PCIS, the higher the serum PCT level,
      resulting in a poorer prognosis. A combination of serum PCT and PCIS can be used
      as an early prognostic indicator in children with sepsis.

PMID- 24568917
TI  - [Impact of continuous blood purification on T cell subsets in children with
      severe sepsis].
AB  - OBJECTIVE: To investigate the impact of continuous blood purification (CBP) on T
      cell subsets and prognosis in children with severe sepsis. METHODS: A total of 42
      children with severe sepsis were randomly divided into a control group (n=22) and
      a CBP group (n=20). The patients in the control group received conventional
      treatment, while those in the CBP group underwent continuous veno-venous
      hemofiltration daily 12-24 hours for 3 days besides conventional treatment.
      Changes in clinical variables and in peripheral blood regulatory T cell subsets
      were assessed 3 and 7 days after treatment. RESULTS: The pediatric intensive care
      unit length of stay and duration of mechanical ventilation were significantly
      shortened and the 28-day mortality rate was significantly lower in the CPB
      treatment group as compared with the control group (P<0.05). In the CBP treatment
      group, the percentage of CD3(+), CD4(+), CD8(+) T cell populations and PCIS
      scores were significantly higher at 3 and 7 days after treatment than before
      treatment (P<0.05). At 7 days after treatment, the percentage of CD3(+), CD4(+),
      CD8(+) T cell populations, CD4(+)/CD8(+) ratio and PCIS scores were significantly
      higher in the CBP group than in the control group (P<0.05). CONCLUSIONS: The CBP
      treatment may counteract the suppression of immune function and thus improve
      prognosis in children with severe sepsis.

PMID- 24568918
TI  - [Down-regulatory effects of budesonide on expression of STAT6 and ORMDL3 in lung
      tissues of asthmatic mice].
AB  - OBJECTIVE: To investigate the roles of signal transduction and activator of
      transcription 6 (STAT6) and orosomucoid 1-like 3 (ORMDL3) in airway remodeling
      among asthmatic mice and to observe the effects of budesonide (BUD) on their
      expression. METHODS: Thirty BALB/c mice were randomly divided into control,
      asthma, and BUD intervention group. The mice were sensitized and challenged with
      ovalbumin (OVA) to establish a mouse model of asthma. The BUD intervention group
      received aerosol inhalation of BUD dissolved in normal saline 30 minutes before
      each OVA challenge, while normal saline was used instead of OVA solution in the
      control group. The pathological changes in the airway were observed by
      hematoxylin-eosin staining and Masson staining. The interleukin-13 (IL-13) level
      in lung homogenate was measured by enzyme-linked immunosorbent assay. The mRNA
      expression of STAT6 and ORMDL3 was measured by RT-PCR. RESULTS: The asthma group
      showed more pathological changes in the airway than the control and BUD
      intervention groups, and the BUD intervention group had reduced pathological
      changes in the airway compared with the asthma group. The asthma and BUD
      intervention groups had significantly higher IL-13 levels and mRNA expression of
      STAT6 and ORMDL3 than the control group (P<0.05), and these indices were
      significantly higher in the asthma group than in the BUD intervention group
      (P<0.05). The Pearson correlation analysis showed that STAT6 mRNA expression was
      positively correlated with ORMDL3 mRNA expression (r=0.676, P=0.032).
      CONCLUSIONS: STAT6 and ORMDL3 may be involved in the airway remodeling of mice,
      and BUD can reduce airway remodeling in asthmatic mice, possibly by down
      regulating mRNA expression of STAT6 and ORMDL3.

PMID- 24568919
TI  - [Protective effects of IGF-1 on cortical nerve cells of neonatal rats under
      oxidative stress].
AB  - OBJECTIVE: To investigate the protective effects of insulin-like growth factor-1
      (IGF-1) on the nerve cells of neonatal rats under oxidative stress. METHODS:
      Primary cortical neurons, oligodendrocytes, and astrocytes from newborn rats were
      cultured. An oxidative stress model was established with different concentrations
      of H2O2 (0-60 MUmol/L); the degree of damage of nerve cells was evaluated by
      lactate dehydrogenase assay, and the viability of nerve cells was tested by MTT
      assay. An oxidative stress model was established with different concentration of
      H2O2 (0-80 MUmol/L). Expression of Akt/p-Akt (Ser473) in neurons was measured by
      Western blot before and after IGF-1 (25 ng/mL) administration. RESULTS: Compared
      with those not treated with H2O2, the cortical neurons, oligodendrocytes, and
      astrocytes treated with different concentrations of H2O2 for 24 hours showed
      increased damage and decreased cell viability; compared with oligodendrocytes and
      astrocytes, neurons showed significantly more changes (P<0.01). Compared with
      those not treated with H2O2, the cortical neurons treated with different
      concentrations of H2O2 for 5 minutes showed a significant decrease in p-Akt
      (Ser473) level (P<0.01), which was dependent on the concentration of H2O2. For
      the neurons treated with low-concentration H2O2, the addition of IGF-1 could
      reverse the inhibition of Akt phosphorylation, eliminating the difference in p
      Akt level compared with the neurons not treated with H2O2, (P>0.05); however, it
      had no significant effect on the inhibition of Akt phosphorylation by high
      concentration H2O2, and the treated neurons still had a lower p-Akt level than
      untreated neurons (P<0.01 for all). For the cortical neurons that had been
      treated with different concentration of H2O2 for 1 hour, the addition of IGF-1
      (25 ng/mL) could eliminate thedifference in p-Akt level between the treated
      neurons and untreated neurons (P>0.05). CONCLUSIONS: Cortical neurons are more
      sensitive to oxidative stress induced by H2O2 than other nerve cells. IGF-1 has
      protective effects on cortical nerve cells under oxidative stress.

PMID- 24568921
TI  - [Role of procalcitonin measurement in the antibiotic therapy in children with
      lower respiratory tract infection].

PMID- 24568920
TI  - [Therapentic efficacy of recombinant human growth hormone in postpuberal children
      with idiopathic short stature].

PMID- 24568922
TI  - [A case report of childhood hematidrosis].

PMID- 24568923
TI  - [A case repot of congenital left pulmonary hypoplasia].

PMID- 24568924
TI  - [Recent advances in the diagnosis and treatment of childhood tuberculosis].
AB  - Tuberculosis (TB) is a chronic infectious disease that seriously harms human
      health and wellbeing. Given its atypical clinical manifestations, TB is hard to
      be diagnosed in clinical settings; to date no highly sensitive screening
      approaches are available. Due to the emergence of multidrug-resistant strains of
      TB (MDR-TB) and limited options for medications in children, the treatment of TB
      is even more challenging in pediatric patients. This paper aims to
      comprehensively review the literature on the recent advances in the research on
      the epidemiology and clinical manifestations of TB, on TB diagnostic approaches
      (e.g., tuberculin skin test, imaging studies, and laboratory tests), and on TB
      treatment in children. 

PMID- 24568925
TI  - Photobleaching as a tool to measure the local strain field in fibrous membranes
      of connective tissues.
AB  - Connective tissues are complex structures which contain collagen and elastin
      fibers. These fiber-based structures have a great influence on material
      mechanical properties and need to be studied at the microscopic scale. Several
      microscopy techniques have been developed in order to image such microstructures;
      among them are two-photon excited fluorescence microscopy and second harmonic
      generation. These observations have been coupled with mechanical characterization
      to link microstructural kinematics to macroscopic material parameter evolution.
      In this study, we present a new approach to measure local strain in soft
      biological tissues using a side-effect of fluorescence microscopy:
      photobleaching. Controlling the loss of fluorescence induced by photobleaching,
      we create a pattern on our sample that we can monitor during mechanical loading.
      The image analysis allows three-dimensional displacements of the patterns at
      various loading levels to be computed. Then, local strain distribution is derived
      using the finite element discretization on a four-node element mesh created from
      our photobleached pattern. Photobleaching tests on a human liver capsule have
      revealed that this technique is non-destructive and does not have any impact on
      mechanical properties. This method is likely to have other applications in
      biological material studies, considering that all collagen-elastin fiber-based
      biological tissues possess autofluorescence properties and thus can be
      photobleached.

PMID- 24568926
TI  - Drug loading into porous calcium carbonate microparticles by solvent evaporation.
AB  - Drug loading into porous carriers may improve drug release of poorly water
      soluble drugs. However, the widely used impregnation method based on adsorption
      lacks reproducibility and efficiency for certain compounds. The aim of this study
      was to evaluate a drug-loading method based on solvent evaporation and
      crystallization, and to investigate the underlying drug-loading mechanisms.
      Functionalized calcium carbonate (FCC) microparticles and four drugs with
      different solubility and permeability properties were selected as model
      substances to investigate drug loading. Ibuprofen, nifedipine, losartan
      potassium, and metronidazole benzoate were dissolved in acetone or methanol.
      After dispersion of FCC, the solvent was removed under reduced pressure. For each
      model drug, a series of drug loads were produced ranging from 25% to 50% (w/w) in
      steps of 5% (w/w). Loading efficiency was qualitatively analyzed by scanning
      electron microscopy (SEM) using the presence of agglomerates and drug crystals as
      indicators of poor loading efficiency. The particles were further characterized
      by mercury porosimetry, specific surface area measurements, differential scanning
      calorimetry, and USP2 dissolution. Drug concentration was determined by HPLC. FCC
      drug mixtures containing equivalent drug fractions but without specific loading
      strategy served as reference samples. SEM analysis revealed high efficiency of
      pore filling up to a drug load of 40% (w/w). Above this, agglomerates and
      separate crystals were significantly increased, indicating that the maximum
      capacity of drug loading was reached. Intraparticle porosity and specific surface
      area were decreased after drug loading because of pore filling and
      crystallization on the pore surface. HPLC quantification of drugs taken up by FCC
      showed only minor drug loss. Dissolution rate of FCC loaded with metronidazole
      benzoate and nifedipine was faster than the corresponding FCC-drug mixtures,
      mainly due to surface enlargement, because only small fractions of amorphous drug
      (12.5%, w/w, and 8.9%, w/w, respectively) were found by thermal analysis.
      Combination of qualitative SEM analysis and HPLC quantification was sufficient to
      proof the feasibility of the solvent-evaporation method for the loading of
      various drugs into FCC. Mechanistic investigation revealed that a high specific
      surface area of the carrier is required to facilitate heterogeneous nucleation,
      and large pore sizes (up to 1 MUm) are beneficial to reduce crystallization
      pressures and allow drug deposition within the pores. The solvent-evaporation
      method allows precise drug loading and appears to be suitable for scale-up.

PMID- 24568927
TI  - Analysis of environmental contamination resulting from catastrophic incidents:
      part 2. Building laboratory capability by selecting and developing analytical
      methodologies.
AB  - Catastrophic incidents can generate a large number of samples of analytically
      diverse types, including forensic, clinical, environmental, food, and others.
      Environmental samples include water, wastewater, soil, air, urban building and
      infrastructure materials, and surface residue. Such samples may arise not only
      from contamination from the incident but also from the multitude of activities
      surrounding the response to the incident, including decontamination. This
      document summarizes a range of activities to help build laboratory capability in
      preparation for sample analysis following a catastrophic incident, including
      selection and development of fit-for-purpose analytical methods for chemical,
      biological, and radiological contaminants. Fit-for-purpose methods are those
      which have been selected to meet project specific data quality objectives. For
      example, methods could be fit for screening contamination in the early phases of
      investigation of contamination incidents because they are rapid and easily
      implemented, but those same methods may not be fit for the purpose of remediating
      the environment to acceptable levels when a more sensitive method is required.
      While the exact data quality objectives defining fitness-for-purpose can vary
      with each incident, a governing principle of the method selection and development
      process for environmental remediation and recovery is based on achieving high
      throughput while maintaining high quality analytical results. This paper
      illustrates the result of applying this principle, in the form of a compendium of
      analytical methods for contaminants of interest. The compendium is based on
      experience with actual incidents, where appropriate and available. This paper
      also discusses efforts aimed at adaptation of existing methods to increase
      fitness-for-purpose and development of innovative methods when necessary. The
      contaminants of interest are primarily those potentially released through
      catastrophes resulting from malicious activity. However, the same techniques
      discussed could also have application to catastrophes resulting from other
      incidents, such as natural disasters or industrial accidents. Further, the high
      sample throughput enabled by the techniques discussed could be employed for
      conventional environmental studies and compliance monitoring, potentially
      decreasing costs and/or increasing the quantity of data available to decision
      makers. 

PMID- 24568928
TI  - Neuroimaging sheds new light on the phonological deficit in dyslexia.
AB  - A new study reports that activations of superior temporal regions for speech are
      normal in dyslexia, although being less well connected to downstream frontal
      regions. These findings support the hypothesis of a deficit in the access to
      phonological representations rather than in the representations themselves. 

PMID- 24568929
TI  - Filling-in versus filling-out: patterns of cortical short-term plasticity.
AB  - Investigations of topographic cortical plasticity following peripheral nervous
      injury predominantly report receptive field (RF) shifts toward the intact
      periphery. A recent study on visual cortex plasticity following retinal lesions
      by Botelho et al.[1] finds RF coverage of the lesion affected space when global
      retinotopic mapping strategies are used. 

PMID- 24568930
TI  - Correlations with longevity and body size: to correct or not correct?

PMID- 24568931
TI  - Vitamin D in relation to cognitive impairment, cerebrospinal fluid biomarkers,
      and brain volumes.
AB  - BACKGROUND: Low vitamin D status is associated with poorer cognitive function in
      older adults, but little is known about the potential impact on cerebrospinal
      fluid (CSF) biomarkers and brain volumes. The objective of this study was to
      examine the relations between plasma 25-hydroxyvitamin D (25(OH)D) and cognitive
      impairment, CSF biomarkers of Alzheimer's disease (AD), and structural brain
      tissue volumes. METHODS: A total of 75 patients (29 with subjective cognitive
      impairment, 28 with mild cognitive impairment, 18 with AD) referred to the Memory
      Clinic at Karolinska University Hospital, Huddinge, Sweden were recruited. Plasma
      25(OH)D, CSF levels of amyloid beta (Abeta(1-42)), total-tau, and phosphorylated
      tau, and brain tissue volumes have been measured. RESULTS: After adjustment for
      several potential confounders, the odds ratios (95% confidence interval) for
      cognitive impairment were as follows: 0.969 (0.948-0.990) per increase of 1
      nmol/L of 25(OH)D and 4.19 (1.30-13.52) for 24(OH)D values less than 50 nmol/L
      compared with values greater than or equal to 50 nmol/L. Adjusting for CSF
      Abeta(1-42) attenuated the 25(OH)D-cognition link. In a multiple linear
      regression analysis, higher 25(OH)D levels were related to higher concentrations
      of CSF Abeta(1-42) and greater brain volumes (eg, white matter, structures
      belonging to medial temporal lobe). The associations between 25(OH)D and tau
      variables were not significant. CONCLUSIONS: This study suggests that vitamin D
      may be associated with cognitive status, CSF Abeta(1-42) levels, and brain tissue
      volumes.

PMID- 24568932
TI  - CD4:8 ratio >5 is associated with a dominant naive T-cell phenotype and impaired
      physical functioning in CMV-seropositive very elderly people: results from the
      BELFRAIL study.
AB  - A subset of older people is at increased risk of hospitalization and dependency.
      Emerging evidence suggests that immunosenescence reflected by an inverted CD4:8
      ratio and cytomegalovirus (CMV) seropositivity plays an important role in the
      pathophysiology of functional decline. Nevertheless, the relation between CD4:8
      ratio and functional outcome has rarely been investigated. Here, CD4:8 ratio and
      T-cell phenotypes of 235 community-dwelling persons aged >=81.5 years in the
      BELFRAIL study and 25 younger persons (mean age 28.5 years) were analyzed using
      polychromatic flow cytometry. In the elderly persons, 7.2% had an inverted CD4:8
      ratio, which was associated with CMV seropositivity, less naive, and more late
      differentiated CD4+ and CD8+ T cells. However, 32.8% had a CD4:8 ratio >5, a
      phenotype associated with a higher proportion of naive T cells and absent in
      young donors. In CMV seropositives, this subgroup had lower proportions of late
      differentiated CD4+ and CD8+ T cells and weaker anti-CMV immunoglobulin G
      reactivity. This novel naive T-cell-dominated phenotype was counterintuitively
      associated with a higher proportion of those with impaired physical functioning
      in the very elderly people infected with CMV. This underscores the notion that in
      very elderly people, not merely CMV infection but also the state of its
      accompanying immune dysregulation is of crucial importance with regard to
      physical impairment. 

PMID- 24568933
TI  - Complete genome sequence of Enterococcus mundtii QU 25, an efficient L-(+)-lactic
      acid-producing bacterium.
AB  - Enterococcus mundtii QU 25, a non-dairy bacterial strain of ovine faecal origin,
      can ferment both cellobiose and xylose to produce l-lactic acid. The use of this
      strain is highly desirable for economical l-lactate production from renewable
      biomass substrates. Genome sequence determination is necessary for the genetic
      improvement of this strain. We report the complete genome sequence of strain QU
      25, primarily determined using Pacific Biosciences sequencing technology. The E.
      mundtii QU 25 genome comprises a 3 022 186-bp single circular chromosome (GC
      content, 38.6%) and five circular plasmids: pQY182, pQY082, pQY039, pQY024, and
      pQY003. In all, 2900 protein-coding sequences, 63 tRNA genes, and 6 rRNA operons
      were predicted in the QU 25 chromosome. Plasmid pQY024 harbours genes for
      mundticin production. We found that strain QU 25 produces a bacteriocin,
      suggesting that mundticin-encoded genes on plasmid pQY024 were functional. For
      lactic acid fermentation, two gene clusters were identified-one involved in the
      initial metabolism of xylose and uptake of pentose and the second containing
      genes for the pentose phosphate pathway and uptake of related sugars. This is the
      first complete genome sequence of an E. mundtii strain. The data provide insights
      into lactate production in this bacterium and its evolution among enterococci. 

PMID- 24568934
TI  - Characteristics of hypertension subtypes and treatment outcome among elderly
      Korean hypertensives.
AB  - There are limited data about characteristics of hypertension subtypes in Asian
      hypertensive patients and their impacts on treatment of hypertension. This
      prospective, multi-center, observational study evaluated 2439 hypertensive
      patients. (>=60 years) Inadequately controlled and drug-naive patients were
      categorized into three hypertension subtypes (isolated systolic hypertension
      [ISH], combined systolic/diastolic hypertension [SDH], and isolated diastolic
      hypertension [IDH]), and proportions of each hypertension subtype were evaluated.
      After 6-month strict treatments, we compared the characteristics of patients who
      did not achieve target BP with those who did. In overall population, ISH was the
      most common subtype (53.2%; 1297/2439). However, in drug-naive patients, SDH was
      the predominant hypertension subtype (59.6%; 260/436). Notably, the proportion of
      ISH was substantially lower than previously known data. Predictors associated
      with failure of reaching target BP were old age (>70 years), hypertension
      awareness, and baseline systolic blood pressure (>=160 mm Hg) for total patients.
      In drug naive patients, hypertension awareness, ISH, and microalbuminuria were
      associated with treatment failure. These findings might have an impact on the
      evaluations and antihypertensive treatments of elderly Korean patients. 

PMID- 24568935
TI  - Second-generation transapical valves: the Medtronic Engager system.
AB  - The Medtronic Engager aortic valve system is a second-generation transcatheter
      aortic valve implantation bioprosthesis combined with a delivery system designed
      for over-the-wire transapical implantation of the valve. The self-expandable
      stent has control arms to be placed into the native aortic sinuses to achieve
      correct positioning of the bioprosthesis in a predefined height. The purpose of
      the lower skirt is to reduce paravalvular leakage. A three-leaflet, bovine
      pericardium valve is mounted on the stent. The implantation is facilitated by the
      control arms and rotational positioning of the commissural posts. A multicentre
      feasibility study showed promising results. The results from the following
      European pivotal trial led to CE mark approval in 2013. Here, we describe
      technical details of the device and its implantation technique and highlight
      special steps of the procedure. 

PMID- 24568936
TI  - Seeking insights about cycling mood disorders via anonymized search logs.
AB  - BACKGROUND: Mood disorders affect a significant portion of the general
      population. Cycling mood disorders are characterized by intermittent episodes (or
      events) of the disease. OBJECTIVE: Using anonymized Web search logs, we identify
      a population of people with significant interest in mood stabilizing drugs (MSD)
      and seek evidence of mood swings in this population. METHODS: We extracted
      queries to the Microsoft Bing search engine made by 20,046 Web searchers over six
      months, separately explored searcher demographics using data from a large
      external panel of users, and sought supporting information from people with mood
      disorders via a survey. We analyzed changes in information needs over time
      relative to searches on MSD. RESULTS: Queries for MSD focused on side effects and
      their relation to the disease. We found evidence of significant changes in search
      behavior and interests coinciding with days that MSD queries are made. These
      include large increases (>100%) in the access of nutrition information,
      commercial information, and adult materials. A survey of patients diagnosed with
      mood disorders provided evidence that repeated queries on MSD may come with
      exacerbations of mood disorder. A classifier predicting the occurrence of such
      queries one day before they are observed obtains strong performance (AUC=0.78).
      CONCLUSIONS: Observed patterns in search behavior align with known behaviors and
      those highlighted by survey respondents. These observations suggest that
      searchers showing intensive interest in MSD may be patients who have been
      prescribed these drugs. Given behavioral dynamics, we surmise that the days on
      which MSD queries are made may coincide with commencement of mania or depression.
      Although we do not have data on mood changes and whether users have been
      diagnosed with bipolar illness, we see evidence of cycling in people who show
      interest in MSD and further show that we can predict impending shifts in behavior
      and interest.

PMID- 24568937
TI  - A validated quantitative liquid chromatography-tandem quadrupole mass
      spectrometry method for monitoring isotopologues to evaluate global modified
      cytosine ratios in genomic DNA.
AB  - 5-Hydroxymethylcytosine (5hmC) and 5-methylcytosine (5mC) represent important
      epigenetic modifications to DNA, and a sensitive analytical method is required to
      determine the levels of 5hmC in the genomic DNA of tumor cells or cultured cell
      lines because 5hmC is present at particular low levels in these cells. We have
      developed a sensitive liquid chromatography-tandem quadrupole mass spectrometric
      method for quantifying 5-hydroxymethyldeoxycytidine (5hmdC), 5
      methyldeoxycytidine (5mdC), and deoxyguanosine (dG) levels using stable isotope
      labeled internal standards, and used this method to estimate the global level of
      2 modified cytosines in genomic DNA prepared from small number of cells. The
      quantification limits for 5hmdC, 5mdC and dG were 20pM, 2nM and 10nM,
      respectively. MRM transitions for isotopologue (isotopologue-MRM) were used to
      quantify the 5mdC and dG levels because of the abundance of these nucleosides
      relative to 5hmdC. The use of isotopologue-MRM for the abundant nucleosides could
      also avoid the saturation of the detector, and allow for all three nucleosides to
      be analyzed simultaneously without the need for the dilution and re-injection of
      samples into the instrument. The global ratios of modified cytosine nucleosides
      to dG were estimated following the quantification of each nucleoside in the
      hydrolysate of genomic DNA. The limit of estimation for the global 5hmC level was
      less than 0.001% using 200ng of DNA. Using this method, we found that MLL-TET1,
      which a fusion protein in acute myelogenous leukemia, did not produce 5hmC, but
      interfered with TET1 activity to produce 5hmC in cells. Our analytical method is
      therefore a valuable tool for further studies aiming at a deeper understanding of
      the role of modified cytosine in the epigenetic regulation of cells. 

PMID- 24568939
TI  - Transport time scales as physical descriptors to characterize heavily modified
      water bodies near ports in coastal zones.
AB  - Physical descriptors that characterize Heavily Modified Water Bodies (HMWB) based
      on the presence of ports should assess the degree of water exchange. The main
      goal of this study is to determine the optimal procedure for estimating Transport
      Time Scales (TTS) as physical descriptors in order to characterize and manage
      HMWB near ports in coastal zones. Flushing Time (FT) and Residence Time (RT),
      using different approaches-analytical and exponential function methods-and
      different hydrodynamic scenarios, were computed using numerical models. El Musel
      (Port of Gijon) was selected to test different transport time scales (FT and RT),
      methods (analytical and exponential function methods) and hydrodynamic conditions
      (wind and tidal forcings). FT, estimated by the exponential function method while
      taking into account a real tidal wave and a mean annual regime of wind as
      hydrodynamic forcing, was determined to be the optimal physical descriptor to
      characterize HMWB. 

PMID- 24568938
TI  - Increasing number of fractured ribs is not predictive of the severity of splenic
      injury following blunt trauma: an analysis of a National Trauma Registry
      database.
AB  - BACKGROUND: Association between rib fractures and incidence of abdominal solid
      organs injury is well described. However, the correlation between the number of
      fractured ribs and severity of splenic injury is not clear. The purpose of this
      study was to assess whether an increasing number of rib fractures predicts the
      severity of splenic injury in blunt trauma patients. STUDY DESIGN: A
      retrospective cohort study involving blunt trauma patients with concomitant
      splenic injuries and rib fractures, between the years 1998 and 2012, registered
      in the Israeli National Trauma Registry. RESULTS: Of 321,618 patients with blunt
      mechanism of trauma, 57,130 had torso injuries, and of these 14,651 patients
      sustained rib fractures, and 3691 patients suffered from splenic injury.
      Concomitant splenic injury occurred in 1326 of the patients with rib fractures
      (9.1%), as compared to 2365 patients sustaining splenic injury without rib
      fractures (5.6%). The incidence of splenic injury among patients sustaining 5 or
      more rib fractures was significantly higher compared to patients suffering from 1
      to 4 rib fractures. Among patients with splenic injury, the tendency to sustain
      associated rib fractures increased steadily with age. Patients with concomitant
      rib fractures had higher Injury Severity Score (ISS), but similar mortality
      rates, compared to patients with splenic injury without rib fractures. Among
      patients with concomitant rib fractures and splenic injury, there was no relation
      between the number of fractured ribs and the severity of splenic injury, neither
      as a whole group, nor after stratification according to the mechanism of injury.
      CONCLUSIONS: Although the presence of rib fractures increases the probability of
      splenic injury in blunt torso trauma, there is no relation between the number of
      fractured ribs and splenic injury severity.

PMID- 24568940
TI  - Energy intensity and the energy mix: what works for the environment?
AB  - In the absence of carbon sequestration, mitigating carbon emissions can be
      achieved through a mix of two broad policy approaches: (i) reducing energy
      intensity by improving energy efficiency and conservation, and (ii) changing the
      fuel mix. This paper investigates the long-run relationship between energy
      intensity, the energy mix, and per capita carbon emissions; while controlling for
      the level of economic activity, the economic structure measured by the relative
      size of the manufacturing sector, and the differences in institutional qualities
      across countries. We aim to answer two particularly important policy questions.
      First, to what extent these policy approaches are effective in mitigating
      emissions in the long-run? Second, which institutional qualities significantly
      contribute to better long-run environmental performance? We use historical data
      for 131 countries in a heterogeneous panel framework for the period 1972-2010. We
      find that less dependence on fossil fuel and lower energy intensity reduce
      emissions in the long run. A goal of 10% reduction in CO2 levels in the long-run
      requires reducing the share of fossil fuel in total energy use by 11%, or
      reducing energy intensity by 13%. In addition, specific institutional qualities
      such as better corruption control and judiciary independence contribute to
      mitigating levels of emissions. 

PMID- 24568941
TI  - Protocol for sortase-mediated construction of DNA-protein hybrids and functional
      nanostructures.
AB  - Recent methods in DNA nanotechnology are enabling the creation of intricate
      nanostructures through the use of programmable, bottom-up self-assembly. However,
      structures consisting only of DNA are limited in their ability to act on other
      biomolecules. Proteins, on the other hand, perform a variety of functions on
      biological materials, but directed control of the self-assembly process remains a
      challenge. While DNA-protein hybrids have the potential to provide the best-of
      both-worlds, they can be difficult to create as many of the conventional
      techniques for linking proteins to DNA render proteins dysfunctional. We present
      here a sortase-based protocol for covalently coupling proteins to DNA with
      minimal disturbance to protein function. To accomplish this we have developed a
      two-step process. First, a small synthetic peptide is bioorthogonally and
      covalently coupled to a DNA oligo using click chemistry. Next, the DNA-peptide
      chimera is covalently linked to a protein of interest under protein-compatible
      conditions using the enzyme sortase. Our protocol allows for the simple coupling
      and purification of a functional DNA-protein hybrid. We use this technique to
      form oligos bearing cadherin-23 and protocadherin-15 protein fragments. Upon
      incorporation into a linear M13 scaffold, these protein-DNA hybrids serve as the
      gate to a binary nanoswitch. The outlined protocol is reliable and modular,
      facilitating the construction of libraries of oligos and proteins that can be
      combined to form functional DNA-protein nanostructures. These structures will
      enable a new class of functional nanostructures, which could be used for
      therapeutic and industrial processes. 

PMID- 24568943
TI  - Case of an appendiceal mucinous adenocarcinoma presenting as a left adnexal mass.
AB  - INTRODUCTION: Appendiceal mucinous neoplasms represent an exceptionally rare form
      of pathology with an incidence rate ranging between 0.2 and 0.3% of all
      appendectomies.(1,2) The most common presentation is right lower quadrant pain
      with a palpable abdominal mass present in 50% of cases.(8-12) Patients may also
      present with nausea, vomiting, change in bowel habits, weight loss, appendicitis,
      intestinal obstruction, ureteral compression, or lower gastrointestinal bleeding.
      Early diagnosis and proper surgical precautions must be implemented to prevent
      iatrogenic rupture of the appendix and the widespread seeding of potentially
      malignant mucin-producing cells throughout the peritoneal cavity. PRESENTATION OF
      CASE: A 50-year-old African-American female presented with complaints of left
      sided pelvic pain. Pelvic examination revealed adnexal fullness with thickening
      behind the cervix. An adnexal mass was revealed on ultrasound and MRI. The
      patient was subsequently taken to the operating room for a planned robotic
      salpingectomy. During the procedure, she was unexpectedly found to have an
      abnormally large appendix displaced to the left lower quadrant. General surgery
      was consulted intra-operatively to perform an appendectomy. The final pathology
      report revealed a low-grade mucinous adenocarcinoma with mucin dissecting into
      the wall of the appendix. DISCUSSION: Appendiceal mucinous cystadenomas are
      characterized by hyperplasia of glandular epithelium along with hypersecretion of
      mucous resulting in a grossly dilated appendix. The clinical manifestation of
      appendiceal mucoceles is often non-specific. The prevalence is higher in women
      than men (4:1) with the average age at the time of diagnosis being 54 years
      old.(14-17) Appendiceal mucinous cystadenomas can be particularly problematic for
      women as these tumors are commonly misdiagnosed pre-operatively as right-sided
      adnexal masses due to commonalities in clinical presentation and diagnostic
      findings.(8-12) It is estimated that based on imaging studies only 15-29% of
      appendiceal mucinous cystadenomas are correctly diagnosed prior to surgical
      intervention.(13) CONCLUSION: To the best of our knowledge, only one other case
      of appendiceal adenocarcinoma with left-sided presentation has been reported.
      Appendiceal carcinomas can create a diagnostic dilemma due to non-specific
      clinical findings and inadequate imaging studies. Early recognition and careful
      intra-operative precautions must be taken to maintain the integrity of the
      appendix to prevent iatrogenic rupture and the spread of potentially malignant
      mucin-producing cells throughout the peritoneal cavity.

PMID- 24568942
TI  - Prefrontal cortex and executive functions in healthy adults: a meta-analysis of
      structural neuroimaging studies.
AB  - Lesion studies link the prefrontal cortex (PFC) to executive functions. However,
      the evidence from in vivo investigations in healthy people is mixed, and there
      are no quantitative estimates of the association strength. To examine the
      relationship between PFC volume and cortical thickness with executive cognition
      in healthy adults, we conducted a meta-analysis of studies that assessed
      executive functions and PFC volume (31 samples,) and PFC thickness (10 samples)
      in vivo, N=3272 participants. We found that larger PFC volume and greater PFC
      thickness were associated with better executive performance. Stronger
      associations between executive functions and PFC volume were linked to greater
      variance in the sample age but was unrelated to the mean age of a sample.
      Strength of association between cognitive and neuroanatomical indices depended on
      the executive task used in the study. PFC volume correlated stronger with
      Wisconsin Card Sorting Test than with digit backwards span, Trail Making Test and
      verbal fluency. Significant effect size was observed in lateral and medial but
      not orbital PFC. The results support the "bigger is better" hypothesis of brain
      behavior relation in healthy adults and suggest different neural correlates
      across the neuropsychological tests used to assess executive functions. 

PMID- 24568946
TI  - Barbajada (coffee, milk and chocolate): the secret to the Nobel Prize.

PMID- 24568944
TI  - Idiopathic hypertonicity as a cause of stiffness after surgery for developmental
      dysplasia of the hip.
AB  - INTRODUCTION: There are various complications reported with surgical treatment of
      DDH. Most studied complication is avascular necrosis of the femoral head and hip
      stiffness. The purpose of this report was to describe a case with severe
      stiffness of the hip due to hypertonicity in periarticular muscles after it was
      treated for developmental dysplasia of the hip (DDH). PRESENTATION OF CASE: Three
      year-old patient referred to our institution with bilateral DDH. Two hips were
      operated separately in one year with anterior open reduction, femoral shortening
      osteotomy. Third month after last surgery, limited right hip range of motion and
      limb length discrepency identified. Clinical examination revealed that patient
      had limited range of motion (ROM) in the right hip and compensated this with
      pelvis obliquity. Gluteus medius, sartorius and iliofemoral band release
      performed after examination under general anesthesia. Symptoms were persisted at
      3rd week control and examination of the patient in general anesthesia revealed
      full ROM without increased tension. For the identified hypertonicity, ultrasound
      guided 100IU botulinum toxin A injection performed to abductor group and
      iliopsoas muscles. Fifth month later, no flexor or abductor tension observed, and
      there was no pelvic obliquity. DISCUSSION: Stiffness as a complication is rare
      and is usually resolved without treatment or simple physical therapy. Usually it
      is related with immobilization or surgery associated joint contracture, and
      spontaneous recovery reported. Presented case is diagnosed as hip stiffness due
      to underlying local hypertonicity. That is resolved with anesthesia and it was
      treated after using botulinum toxin A injection. CONCLUSION: Hypertonicity with
      hip stiffness after surgical treatment of DDH differ from spontaneous recovering
      hip range of motion limitation and treatment can only be achieved by reduction of
      the muscle hypertonicity by neuromuscular junction blockage.

PMID- 24568945
TI  - Preparatory study for the revaluation of the EQ-5D tariff: methodology report.
AB  - BACKGROUND: EQ-5D is a widely used generic measure of health with a 'tariff', or
      preference weights, obtained from the general population, using time trade-off
      (TTO). PRET (Preparatory study for the Re-valuation of the EQ-5D Tariff project)
      contributes towards the methodology for its revaluation. METHODS: Stage 1
      examined key assumptions typically involved in health-state valuations through a
      series of binary choice exercises, namely that health-state preferences are
      independent of (1) duration of the state; (2) whose health it is (i.e.
      perspective); (3) length of 'lead time' (a mechanism to value all states on the
      same scale, including those who are worse than being dead); (4) when health
      events take place (time preference); and (5) satisfaction associated with the
      state. Further topics addressed were (6) exhaustion of lead time in the worst
      state; (7) health-state valuation using discrete choice experiments (DCEs) with a
      duration attribute; and (8) binary choice administration of lead time - time
      trade-off (LT-TTO). Stage 1 consisted of an online survey with 6000 respondents.
      Stage 2 compared the results above to those of an identical survey conducted in
      200 face-to-face computer-assisted personal interviews (CAPIs), covering topics
      (1) to (7). Stages 3 and 4 examined - in more detail and depth - issues taken
      from stage 1. Stage 3 consisted of CAPI surveys of a representative UK sample of
      300, using examples of TTO, LT-TTO, and DCE with duration, each followed by
      extensive feedback questions. Stage 4 was a more intensive exercise involving a
      qualitative analysis of people's thought processes during both binary choice and
      iterative health-state valuation exercises. Data were collected through 'think
      aloud' methods in 30 interviews of a convenience sample. RESULTS: Stage 1 found
      that health-state values are not independent of (1) duration of the state but
      there is no clear pattern; (2) whose health it is; (3) the duration of 'lead
      time' but there was no clear pattern; (4) when health events take place; or (5)
      satisfaction associated with the state. Furthermore, (6) exhaustion of lead time
      in the worst state was subject to substantial framing effects; (7) the five-level
      version of the EQ-5D (EQ-5D-5L) can be valued using DCE with duration as an
      attribute; and (8) binary choice LT-TTO can be administered in an online
      environment. Stage 2 found that although online surveys and CAPI surveys resulted
      in different compositions of respondents, at the aggregate, their responses to
      the experimental questions covering (1) to (7) above were not statistically
      significantly different from each other. Stages 3 and 4 found that TTO and LT-TTO
      were easier than DCE with duration; respondents did not necessarily trade across
      all attributes of EQ-5D; some respondents found it difficult to distinguish
      between the two worst levels of EQ-5D-5L, and some respondents may be thinking
      about the impact of their ill health on their family. CONCLUSIONS: In order for
      the National Institute for Health and Care Excellence to make the most
      appropriate decisions, the EQ-5D tariff needs to incorporate the latest
      understanding of health-state preferences. PRET contributed to the knowledge base
      on the conduct of health-state valuation studies. FUNDING: The Medical Research
      Council (MRC)-National Institute for Health Research (NIHR) Methodology Research
      Programme funded the PRET project (MRC ref. G0901500), and the EuroQol Group
      funded the PRET-AS project (Preparatory study for the Re-valuation of the EQ-5D
      Tariff project - Additional Sample) as an extension to the PRET project with
      formal agreement from the MRC.

PMID- 24568947
TI  - MDCT interpretation of the ascending aorta with semiautomated measurement
      software: improved reproducibility compared with manual techniques.
AB  - BACKGROUND: Treatment decisions for ascending aortic aneurysms are guided by
      measurements from CT angiograms. OBJECTIVE: The aim was to evaluate the
      reproducibility of these measurements by using manual techniques and advanced
      imaging software. METHODS: Two radiologists measured maximal ascending aorta
      diameter on CT angiograms in 30 subjects at 4 separate reading sessions-2 with
      manual techniques and 2 with semiautomated software analysis. Interobserver and
      intraobserver variabilities were assessed with Bland-Altman plots and Spearman
      correlation coefficients. RESULTS: Interobserver variability was smaller for the
      software-assisted method. Limits of agreement for the manual method were -4.2 mm
      and 9.2 mm compared with -4.0 mm and 4.6 mm for the software-assisted method;
      coefficients of repeatability were 6.8 mm and 4.3 mm. Intraobserver variability
      was inconsistent between readers. Strong correlation was found between observers
      who used both methods (R(2) = 0.8078-0.9881; P < .05 for all). CONCLUSION: The
      use of an advanced imaging software for measurement of ascending aortic aneurysm
      reduces interobserver variability.

PMID- 24568949
TI  - Efficacy and safety of auriculopressure for primary care patients with chronic
      non-specific spinal pain: a multicentre randomised controlled trial.
AB  - BACKGROUND: Chronic uncomplicated musculoskeletal pain in the spine (cervical,
      thoracic or lumbar) is highly prevalent and may severely limit the daily
      activities of those affected by it. OBJECTIVE: To evaluate the efficacy and
      safety of treatment with auriculopressure applied to patients with non-specific
      spinal pain. METHODS: A multicentre randomised controlled trial with two parallel
      arms (true auriculopressure (TAP) and placebo auriculopressure (PAP)) was
      performed. The intervention phase lasted 8 weeks and outcomes were measured 1
      week after the last intervention (T1) and 6 months after baseline (T2). The
      primary outcome measure was change in pain intensity according to a 100 mm visual
      analogue scale (pain VAS) at T1. Secondary outcome measures were the Lattinen
      index, the McGill Pain Questionnaire and the SF-12 health-related quality of life
      scale (Spanish version in every case). RESULTS: There were 265 participants (TAP
      group, n=130; PAP group, n=135). Pain was most frequently located in the upper
      back (55.1%, n=146), followed by the lower back (25.3%, n=67) and the dorsal area
      (12.5%, n=33). Nineteen patients (7.2%) reported pain affecting the entire spine.
      There were statistically significant differences between TAP and PAP in the
      change in the pain VAS at T1 of 10 mm (95% CI 2.8 to 17.3, p=0.007) and in the
      change in the pain VAS at T2 of 7.2 mm (95% CI 0.02 to 14.3, p=0.049) in favour
      of TAP. We also observed a statistically significant difference of 3.4 points in
      the physical component of the SF-12 in favour of TAP at T2 (95% CI 0.45 to 6.3,
      p=0.024). No severe adverse effects were detected or reported during treatment.
      CONCLUSIONS: The application of auriculopressure in patients with non-specific
      spinal pain in primary healthcare is effective and safe, and therefore should be
      considered for inclusion in the portfolio of primary healthcare services. TRIAL
      REGISTRATION NUMBER: ISRCTN01897462.

PMID- 24568948
TI  - The Cryptochrome/Photolyase Family in aquatic organisms.
AB  - The Cryptochrome/Photolyase Family (CPF) represents an ancient group of widely
      distributed UV-A/blue-light sensitive proteins sharing common structures and
      chromophores. During the course of evolution, different CPFs acquired distinct
      functions in DNA repair, light perception and circadian clock regulation.
      Previous phylogenetic analyses of the CPF have allowed reconstruction of the
      evolution and distribution of the different CPF super-classes in the tree of
      life. However, so far only limited information is available from the CPF
      orthologs in aquatic organisms that evolved in environments harboring great
      diversity of life forms and showing peculiar light distribution and rhythms. To
      gain new insights into the evolutionary and functional relationships within the
      CPF family, we performed a detailed study of CPF members from marine (diatoms,
      sea urchin and annelid) and freshwater organisms (teleost) that populate diverse
      habitats and exhibit different life strategies. In particular, we first extended
      the CPF family phylogeny by including genes from aquatic organisms representative
      of several branches of the tree of life. Our analysis identifies four major super
      classes of CPF proteins and importantly singles out the presence of a plant-like
      CRY in diatoms and in metazoans. Moreover, we show a dynamic evolution of Cpf
      genes in eukaryotes with various events of gene duplication coupled to functional
      diversification and gene loss, which have shaped the complex array of Cpf genes
      in extant aquatic organisms. Second, we uncover clear rhythmic diurnal expression
      patterns and light-dependent regulation for the majority of the analyzed Cpf
      genes in our reference species. Our analyses reconstruct the molecular evolution
      of the CPF family in eukaryotes and provide a solid foundation for a systematic
      characterization of novel light activated proteins in aquatic environments. 

PMID- 24568950
TI  - Recycling of asbestos tailings used as reinforcing fillers in polypropylene based
      composites.
AB  - In this work, asbestos tailings were recycled and used as reinforcing fillers to
      enhance the mechanical properties of polypropylene (PP). A silane coupling agent
      was used to chemically modify the asbestos tailings to increase the compatibility
      between asbestos tailings and polypropylene matrix. Both raw and chemically
      treated asbestos tailings with different loading levels (from 3 to 30 wt%) were
      utilized to fabricate composites. Mechanical properties of these composites have
      been investigated by dynamic mechanical analysis, tensile test and notched impact
      test. Results showed that hybridization of asbestos tailings in the composites
      enhanced the mechanical properties of neat PP evidently, and treated asbestos
      tailings/PP composites yielded even better mechanical properties compared with
      those of raw asbestos tailings/PP composites. This recycling method of asbestos
      tailings not only reduces disposal costs and avoids secondary pollution but also
      produces a new PP-based composite material with enhanced mechanical properties.

PMID- 24568951
TI  - Preliminary study of acoustic analysis for evaluating speech-aid oral prostheses:
      Characteristic dips in octave spectrum for comparison of nasality.
AB  - BACKGROUND/PURPOSE: Acoustic analysis is often used in speech evaluation but
      seldom for the evaluation of oral prostheses designed for reconstruction of
      surgical defect. This study aimed to introduce the application of acoustic
      analysis for patients with velopharyngeal insufficiency (VPI) due to oral surgery
      and rehabilitated with oral speech-aid prostheses. METHODS: The pre- and
      postprosthetic rehabilitation acoustic features of sustained vowel sounds from
      two patients with VPI were analyzed and compared with the acoustic analysis
      software Praat. RESULTS: There were significant differences in the octave
      spectrum of sustained vowel speech sound between the pre- and postprosthetic
      rehabilitation. Acoustic measurements of sustained vowels for patients before and
      after prosthetic treatment showed no significant differences for all parameters
      of fundamental frequency, jitter, shimmer, noise-to-harmonics ratio, formant
      frequency, F1 bandwidth, and band energy difference. The decrease in objective
      nasality perceptions correlated very well with the decrease in dips of the
      spectra for the male patient with a higher speech bulb height. CONCLUSION:
      Acoustic analysis may be a potential technique for evaluating the functions of
      oral speech-aid prostheses, which eliminates dysfunctions due to the surgical
      defect and contributes to a high percentage of intelligible speech. Octave
      spectrum analysis may also be a valuable tool for detecting changes in nasality
      characteristics of the voice during prosthetic treatment of VPI.

PMID- 24568952
TI  - Acu-TENS might alleviate the dysfunction following spinal cord injury.

PMID- 24568955
TI  - Quality of life of infertile Tunisian couples and differences according to
      gender.
AB  - OBJECTIVE: To compare quality-of-life gender differences within infertile couples
      from Tunisia and between infertile couples and controls. METHODS: The present
      case-control study included 100 couples with primary infertility who, during
      2009, underwent assisted reproductive technology at Farhat Hached Hospital in
      Sousse, Tunisia, and 100 control couples. The 36-item Short-Form Health Survey
      (SF-36) was administered to assess quality of life. RESULTS: Compared with male
      controls, men in the infertility group had lower scores in the mental dimension
      (P=0.020), social functioning (P=0.007), and role-emotional (P<0.001) categories
      of the SF-36. Women in the infertility group had lower mental and physical
      dimension scores (P<0.001) and lower vitality (P=0.022), social functioning
      (P<0.001), role-emotional (P<0.001), and mental health (P<0.001) scores than
      female controls. Within infertile couples, female partners had lower total
      (P=0.01) and mental dimension (P<0.001) scores than their spouses. Delay of the
      first consultation was correlated with bodily pain, vitality, and mental health
      among women in the infertility group. CONCLUSION: Women in infertile couples had
      a lower quality of life than their spouses, and infertile couples had a lower
      quality of life than controls. These findings confirm the need for psychological
      support for infertile couples.

PMID- 24568954
TI  - A soluble mutant of the transmembrane receptor Af1503 features strong changes in
      coiled-coil periodicity.
AB  - Structures of full-length, membrane-bound proteins are essential for
      understanding transmembrane signaling mechanisms. However, in prokaryotic
      receptors no such structure has been reported, despite active research for many
      years. Here we present results of an alternative strategy, whereby a
      transmembrane receptor is made soluble by selective mutations to the membrane
      spanning region, chosen by analysis of helix geometry in the transmembrane
      regions of chemotaxis receptors. We thus converted the receptor Af1503 from
      Archaeoglobus fulgidus to a soluble form by deleting transmembrane helix 1 and
      mutating the surface residues of transmembrane helix 2 to hydrophilic amino
      acids. Crystallization of this protein resulted in the structure of a tetrameric
      proteolytic fragment representing the modified transmembrane helices plus the
      cytoplasmic HAMP domain, a ubiquitous domain of prokaryotic signal transducers.
      The protein forms a tetramer via native parallel dimerization of the HAMP domain
      and non-native antiparallel dimerization of the modified transmembrane helices.
      The latter results in a four-helical coiled coil, characterized by unusually
      large changes in helix periodicity. The structure offers the first view of the
      junction between the transmembrane region and HAMP and explains the conservation
      of a key sequence motif in HAMP domains. 

PMID- 24568956
TI  - Rabies in a pregnant woman and delivery of a live fetus.

PMID- 24568957
TI  - Abnormal cervical cytology among HIV-positive women in Nigeria.
AB  - OBJECTIVE: To determine the prevalence of abnormal cervical smears and high-grade
      lesions among HIV-positive and HIV-negative women, and to assess the relationship
      between severity of disease and CD4 count. METHODS: In a prospective cross
      sectional comparative study, 250 HIV-positive and 250 HIV-negative women
      attending the University of Port Harcourt Teaching Hospital, Port Harcourt,
      Nigeria, were enrolled between January and March 2012. Cervical smear samples
      were collected from participants, examined, and reported via the Bethesda system.
      Data management and analysis was done with SPSS. Differences between the 2 study
      groups were determined by chi2 test and Student t test. RESULTS: The prevalence
      of abnormal cervical smears was significantly higher among HIV-positive women
      (34.4%) than among HIV-negative women (20.2%) (P<0.01). The proportion of high
      grade lesions was significantly higher among HIV-positive women (23.5%) than
      among HIV-negative women (8.2%) (P=0.025). HIV-positive women with a CD4 count
      below 500 cells/mm3 had significantly more abnormal cervical smears (28.3%)
      compared with those with a CD4 count of 500 cells/mm3 or more (6.1%) (P=0.04).
      CONCLUSION: HIV-positive women were found to be at significantly greater risk of
      developing abnormal cervical cytology and high-grade lesions compared with HIV
      negative women.

PMID- 24568958
TI  - Pregnancy and long-term cardiovascular outcomes in women with congenitally
      corrected transposition of the great arteries.
AB  - OBJECTIVE: To define maternal/neonatal outcomes and long-term cardiovascular
      effects of pregnancy in women with congenitally corrected transposition of the
      great arteries (ccTGA). METHODS: Clinical records of all women with ccTGA who
      were followed at a tertiary care center in Poland between April 1991 and April
      2012 were retrospectively reviewed. RESULTS: Of the 20 pregnancies among 13 women
      identified, 19 (95%) were successful. Of the 19 deliveries, 14 (74%) were vaginal
      and 5 (26%) were cesarean. Cardiovascular complications during pregnancy and
      childbirth occurred in 3 patients (16% of successful pregnancies). Two women
      developed supraventricular arrhythmias; they were observed and required no
      pharmacologic treatment. One patient required premature delivery for documented
      deterioration of right ventricular function. There were no pregnancy-related
      maternal deaths. In 1 case, congenital heart disease was diagnosed in the
      offspring. With regard to long-term follow-up, no differences were found in terms
      of heart failure admissions, pharmacologic treatment, deaths, or
      echocardiographic parameters compared with non-pregnant women with ccTGA.
      CONCLUSION: Successful pregnancy can be achieved by most women with ccTGA. The
      most common cardiovascular complications are supraventricular arrhythmias but
      pregnancy does not seem to impair right ventricular function in the long term.
      Nevertheless, preconception counseling and tertiary care during pregnancy for
      women with ccTGA are recommended.

PMID- 24568959
TI  - Men's and women's experiences of violence and traumatic events in rural Cote
      d'Ivoire before, during and after a period of armed conflict.
AB  - OBJECTIVE: We assessed men's and women's experiences of gender based violence and
      other traumatic events in Cote d'Ivoire, a West African conflict-affected
      setting, before, during and after a period of active armed conflict (2000-2007).
      DESIGN: Cross-sectional, household survey. SETTING: 12 rural communities directly
      impacted by the Crisis in Cote d'Ivoire, spanning regions controlled by
      government forces, rebels and UN peacekeepers in 2008. PARTICIPANTS: 2678 men and
      women aged 15-49 years. PRIMARY OUTCOME MEASURES: Violence exposures measured
      since age 15. Questions included intimate partner physical and sexual violence;
      physical and sexual violence by others (including combatants) and exposure to
      traumatic events before, during and after the Crisis period (2000-2007). RESULTS:
      Physical and/or sexual violence since age 15 was reported by 57.1% women and
      40.2% men (p=0.01); 29.9% women and 12.3% men reported exposure to any violence
      in the past year. Nearly 1 in 10 women (9.9%) and 5.9% men (p=0.03) were forced
      to have sex by a non-partner since age 15, and 14.8% women and 3.3% men (p=0.00)
      reported their first sexual experience was forced. Combatants were rarely
      reported as sexual violence perpetrators (0.3% women). After the Crisis, intimate
      partner physical violence was the most frequently reported form of violence and
      highest among women (20.9% women, 9.9% men, p=0.00). Fearing for their life was
      reported by men and women before, during and after the Crisis. CONCLUSIONS:
      Sexual violence in conflict remains a critical international policy concern.
      However, men and women experience different types of violence before, during and
      after conflict. In many conflict settings, other forms of violence, including
      intimate partner violence, may be more widespread than conflict-related sexual
      violence. Alongside service provision for rape survivors, our findings underscore
      the need for postconflict reconstruction efforts to invest in programmes to
      prevent and respond to intimate partner violence and trauma.

PMID- 24568960
TI  - Patient-reported confidence in primary healthcare: are there disparities by
      ethnicity or language?
AB  - OBJECTIVE: To examine whether confidence in primary healthcare (PHC) differs
      among ethnic-linguistic groups and which PHC experiences are associated with
      confidence. DESIGN: A cross-sectional study where patient surveys were
      administered using random digit dialling. Regression models identify whether
      ethnic-linguistic group remains significantly associated with confidence in PHC.
      SETTING: British Columbia, Canada. MAIN OUTCOME MEASURES: Confidence in PHC
      measured using a 0-10 scale, where a higher score indicates increased confidence
      in the ability to get needed PHC services. PARTICIPANTS: Community-dwelling
      adults in the following ethnic-linguistic groups: English-speaking Chinese,
      Chinese-speaking Chinese, English-speaking South Asians, Punjabi-speaking South
      Asians and English-speakers of presumed European descent. FINDINGS: Based on a
      sample of 1211 respondents, confidence in PHC differed by ethnicity and the
      ability to speak English. Most of the differences in confidence by ethnic
      linguistic group can be explained by various aspects of care experience. Patient
      experiences associated with lower confidence in PHC were: if care was received
      outside Canada, having to wait months to see their regular doctor and rating the
      quality of healthcare as good or fair/poor. Better patient experiences of their
      doctor being concerned about their feelings and being respectful and if they
      found wait times acceptable were associated with higher levels of confidence in
      PHC. The final regression model explained 30% of the variance. CONCLUSIONS:
      Improving the delivery of PHC services through positive interactions between
      patients and their usual provider and acceptability of wait times are examples of
      how the PHC system can be strengthened.

PMID- 24568961
TI  - Job stress and burnout in hospital employees: comparisons of different medical
      professions in a regional hospital in Taiwan.
AB  - OBJECTIVES: To explore the prevalence and associated factors of burnout among
      five different medical professions in a regional teaching hospital. DESIGN: Cross
      sectional study. SETTING: Hospital-based survey. PARTICIPANTS: A total of 1329
      medical professionals were recruited in a regional hospital with a response rate
      of 89%. These voluntary participants included 101 physicians, 68 physician
      assistants, 570 nurses, 216 medical technicians and 374 administrative staff.
      PRIMARY AND SECONDARY OUTCOME MEASURES: Demographic data included gender, age,
      level of education and marital status, and work situations, such as position,
      work hours and work shifts, were obtained from an electronic questionnaire. Job
      strain and burnout were measured by two validated questionnaires, the Chinese
      version of the Job Content Questionnaire and the Copenhagen Burnout Inventory.
      RESULTS: Among the five medical professions, the prevalence of high work-related
      burnout from highest to lowest was nurses (66%), physician assistants (61.8%),
      physicians (38.6%), administrative staff (36.1%) and medical technicians (31.9%),
      respectively. Hierarchical regression analysis indicated that job strain,
      overcommitment and low social support explained the most variance (32.6%) of
      burnout. CONCLUSIONS: Physician assistant is an emerging high burnout group; its
      severity is similar to that of nurses and far more than that of physicians,
      administrative staff and medical technicians. These findings may contribute to
      the development of feasible strategies to reduce the stress which results in the
      burnout currently plaguing most hospitals in Taiwan.

PMID- 24568962
TI  - Methodological characteristics and treatment effect sizes in oral health
      randomised controlled trials: Is there a relationship? Protocol for a meta
      epidemiological study.
AB  - INTRODUCTION: It is fundamental that randomised controlled trials (RCTs) are
      properly conducted in order to reach well-supported conclusions. However, there
      is emerging evidence that RCTs are subject to biases which can overestimate or
      underestimate the true treatment effect, due to flaws in the study design
      characteristics of such trials. The extent to which this holds true in oral
      health RCTs, which have some unique design characteristics compared to RCTs in
      other health fields, is unclear. As such, we aim to examine the empirical
      evidence quantifying the extent of bias associated with methodological and non
      methodological characteristics in oral health RCTs. METHODS AND ANALYSIS: We plan
      to perform a meta-epidemiological study, where a sample size of 60 meta-analyses
      (MAs) including approximately 600 RCTs will be selected. The MAs will be randomly
      obtained from the Oral Health Database of Systematic Reviews using a random
      number table; and will be considered for inclusion if they include a minimum of
      five RCTs, and examine a therapeutic intervention related to one of the
      recognised dental specialties. RCTs identified in selected MAs will be
      subsequently included if their study design includes a comparison between an
      intervention group and a placebo group or another intervention group. Data will
      be extracted from selected trials included in MAs based on a number of
      methodological and non-methodological characteristics. Moreover, the risk of bias
      will be assessed using the Cochrane Risk of Bias tool. Effect size estimates and
      measures of variability for the main outcome will be extracted from each RCT
      included in selected MAs, and a two-level analysis will be conducted using a meta
      meta-analytic approach with a random effects model to allow for intra-MA and
      inter-MA heterogeneity. ETHICS AND DISSEMINATION: The intended audiences of the
      findings will include dental clinicians, oral health researchers, policymakers
      and graduate students. The aforementioned will be introduced to the findings
      through workshops, seminars, round table discussions and targeted individual
      meetings. Other opportunities for knowledge transfer will be pursued such as key
      dental conferences. Finally, the results will be published as a scientific report
      in a dental peer-reviewed journal.

PMID- 24568964
TI  - Comparison of the Anyplex II HPV28 assay with the Hybrid Capture 2 assay for the
      detection of HPV infection.
AB  - BACKGROUND: Human papillomavirus (HPV) testing is an important part of cervical
      cancer screening and management of women with abnormal cytology results. The
      Hybrid Capture 2 (HC2) has been recommended for use as a reference test.
      OBJECTIVE: To evaluate a new real-time PCR assay (Anyplex II HPV28) for detecting
      high risk (HR) HPV and to compare it to the HC2. In addition, we compared the
      genotyping results of the Anyplex II HPV28 to those of sequencing analysis. STUDY
      DESIGN: A total of 1114 cervical swab specimens were consecutively obtained from
      a single healthcare center. We submitted all specimens for HPV detection with
      Anyplex II HPV28 and HC2, then analyzed the discordant results using multiplex
      PCR followed by direct sequencing. RESULTS: HC2 detected 72 (6.5%) cases with HR
      HPV, while Anyplex II HPV28 identified 138 (12.4%) cases. The overall agreement
      rate was 91.4% (1018/1114) of cases. Discordant results between these two assays
      were observed in 96 cases; 15 were positive only by HC2, and 81 were positive
      only by Anyplex II HPV28. Sequencing analyses performed in 80 cases of discordant
      results revealed 11 false-positive, and 67 false-negative results using HC2 tests
      and two false-positive results using Anyplex II HPV28. CONCLUSIONS: The Anyplex
      II HPV28 assay is analytically more sensitive in the detection of the 13 HR types
      represented by the HC2 assay and exhibited a higher concordance with
      comprehensive genotyping based on the sequencing analysis, and it could be used
      as a laboratory testing method for identifying HPV genotypes.

PMID- 24568963
TI  - Aspirin and clonidine in non-cardiac surgery: acute kidney injury substudy
      protocol of the Perioperative Ischaemic Evaluation (POISE) 2 randomised
      controlled trial.
AB  - INTRODUCTION: Perioperative Ischaemic Evaluation-2 (POISE-2) is an international
      2*2 factorial randomised controlled trial of low-dose aspirin versus placebo and
      low-dose clonidine versus placebo in patients who undergo non-cardiac surgery.
      Perioperative aspirin (and possibly clonidine) may reduce the risk of
      postoperative acute kidney injury (AKI). METHODS AND ANALYSIS: After receipt of
      grant funding, serial postoperative serum creatinine measurements began to be
      recorded in consecutive patients enrolled at substudy participating centres. With
      respect to the study schedule, the last of over 6500 substudy patients from 82
      centres in 21 countries were randomised in December 2013. The authors will use
      logistic regression to estimate the adjusted OR of AKI following surgery
      (compared with the preoperative serum creatinine value, a postoperative increase
      >=26.5 MUmol/L in the 2 days following surgery or an increase of >=50% in the 7
      days following surgery) comparing each intervention to placebo, and will report
      the adjusted relative risk reduction. Alternate definitions of AKI will also be
      considered, as will the outcome of AKI in subgroups defined by the presence of
      preoperative chronic kidney disease and preoperative chronic aspirin use. At the
      time of randomisation, a subpopulation agreed to a single measurement of serum
      creatinine between 3 and 12 months after surgery, and the authors will examine
      intervention effects on this outcome. ETHICS AND DISSEMINATION: The authors were
      competitively awarded a grant from the Canadian Institutes of Health Research for
      this POISE-2 AKI substudy. Ethics approval was obtained for additional kidney
      data collection in consecutive patients enrolled at participating centres, which
      first began for patients enrolled after January 2011. In patients who provided
      consent, the remaining longer term serum creatinine data will be collected
      throughout 2014. The results of this study will be reported no later than 2015.
      CLINICAL TRIAL REGISTRATION NUMBER: NCT01082874.

PMID- 24568965
TI  - Cerebral vasculitis and encephalitis due to Epstein-Barr virus in a patient with
      newly diagnosed HIV infection.
AB  - Epstein-Barr virus (EBV) is a common infection which usually produces mild or no
      symptoms in immunocompetent individuals. In human immunodeficiency virus (HIV)
      associated immunosuppression it is most commonly associated with malignancy which
      usually occurs at very low CD4+ cell counts. We describe a newly diagnosed HIV
      positive patient who presented with headaches and cerebellar signs. She was
      incorrectly diagnosed with cerebral tuberculosis (TB) infection based on the
      histology report from a cerebellar biopsy specimen. After extensive investigation
      including cerebrospinal fluid sampling and reanalysis of the brain biopsy
      specimens she was found to have EBV-associated cerebral vasculitis and
      encephalitis and was successfully treated with valganciclovir and steroids.
      Whilst there are a few reports of EBV-associated encephalitis, cerebral
      vasculitis secondary to EBV in the context of HIV infection has not previously
      been described in the literature. 

PMID- 24568966
TI  - Effect of mandibular distraction osteogenesis on the temporomandibular joint: a
      systematic review of animal experimental studies.
AB  - OBJECTIVE: The present systematic review aimed to test the hypothesis of no
      effect of mandibular distraction osteogenesis on the temporomandibular joint.
      STUDY DESIGN: Animal experimental studies from January 1985 to August 2013 were
      included. Studies were searched in PubMed, Embase, Scopus, and the Cochrane
      Library. A total of 289 articles were identified, and 17 were included. RESULTS:
      Included studies were characterized by a high risk of bias and by inhomogeneity
      related to animal species, experimental procedures, and evaluation methods.
      Mandibular distraction osteogenesis within physiologic limits may be followed by
      adaptive changes in bone, disk, and cartilage. Increased daily rates and total
      activation length may influence the severity of the adaptive changes.
      CONCLUSIONS: Animal experimental studies indicate that mandibular distraction
      osteogenesis may induce adaptive changes in the temporomandibular joint. Adaptive
      changes may be influenced by increased daily rates and total length of
      distraction osteogenesis. Well-designed studies are needed before final
      conclusions can be drawn.

PMID- 24568967
TI  - Investigating tooth loss and associated factors among older Taiwanese adults.
AB  - The aim of this study was to evaluate factors associated with tooth loss in older
      Taiwanese adults with different numbers of remaining teeth. This study evaluated
      oral health status and tooth loss among 2286 adults aged over 65. Subjects were
      classified according to number of teeth (Group 1 <20 teeth vs. Group 2 >=20
      teeth). Tooth loss and oral health data were collected from the National Health
      Interview Survey (NHIS), compared between groups and analyzed by multivariate
      modeling. Group 1 subjects were older and had more partial dentures. Tooth loss
      was associated with self-limited food choices due to oral health status, and
      malnutrition. Tooth loss in Group 2 subjects was significantly associated with
      lower mental status. Tooth loss may predict cognitive status (odds ratio (OR)
      1.30) and physical-disability (OR 1.79). Our results suggested that tooth loss
      was associated with age, more partial dentures, self-limited food choices,
      malnutrition, and lower mental and cognitive status and physical disability. 

PMID- 24568968
TI  - The G protein-coupled receptor GALR2 promotes angiogenesis in head and neck
      cancer.
AB  - Squamous cell carcinoma of the head and neck (SCCHN) is an aggressive disease
      with poor patient survival. Galanin receptor 2 (GALR2) is a G protein-coupled
      receptor that induces aggressive tumor growth in SCCHN. The objective of this
      study was to investigate the mechanism by which GALR2 promotes angiogenesis, a
      critical oncogenic phenotype required for tumor growth. The impact of GALR2
      expression on secretion of proangiogenic cytokines in multiple SCCHN cell lines
      was investigated by ELISA and in vitro angiogenesis assays. Chemical inhibitor
      and genetic knockdown strategies were used to understand the key regulators. The
      in vivo impact of GALR2 on angiogenesis was investigated in mouse xenograft,
      chick chorioallantoic membrane, and the clinically relevant mouse orthotopic
      floor-of-mouth models. GALR2 induced angiogenesis via p38-MAPK-mediated secretion
      of proangiogenic cytokines, VEGF, and interleukin-6 (IL-6). Moreover, GALR2
      activated small-GTP-protein, RAP1B, thereby inducing p38-mediated inactivation of
      tristetraprolin (TTP), which functions to destabilize cytokine transcripts. This
      resulted in enhanced secretion of proangiogenic cytokines and angiogenesis in
      vitro and in vivo. In SCCHN cells overexpressing GALR2, inactivation of TTP
      increased secretion of IL-6 and VEGF, whereas inhibition of p38 activated TTP and
      decreased cytokine secretion. Here, we report that GALR2 stimulates tumor
      angiogenesis in SCCHN via p38-mediated inhibition of TTP with resultant enhanced
      cytokine secretion. Given that p38 inhibitors are in clinical use for
      inflammatory disorders, GALR2/p38-mediated cytokine secretion may be an excellent
      target for new adjuvant therapy in SCCHN.

PMID- 24568969
TI  - Preclinical pharmacological evaluation of a novel multiple kinase inhibitor,
      ON123300, in brain tumor models.
AB  - ON123300 is a low molecular weight multikinase inhibitor identified through a
      series of screens that supported further analyses for brain tumor chemotherapy.
      Biochemical assays indicated that ON123300 was a strong inhibitor of Ark5 and
      CDK4, as well as growth factor receptor tyrosine kinases such as beta-type
      platelet-derived growth factor receptor (PDGFRbeta). ON123300 inhibited U87
      glioma cell proliferation with an IC(50) 3.4 +/- 0.1 MUmol/L and reduced
      phosphorylation of Akt, yet it also unexpectedly induced Erk activation, both in
      a dose- and time-dependent manner that subsequently was attributed to relieving
      Akt-mediated C-Raf S259 inactivation and activating a p70S6K-initiated PI3K
      negative feedback loop. Cotreatment with the EGFR inhibitor gefitinib produced
      synergistic cytotoxic effects. Pursuant to the in vitro studies, in vivo
      pharmacokinetic and pharmacodynamic studies of ON123300 were completed in mice
      bearing intracerebral U87 tumors following intravenous doses of 5 and 25 mg/kg
      alone, and also at the higher dose concurrently with gefitinib. ON123300 showed
      high brain and brain tumor accumulation based on brain partition coefficient
      values of at least 2.5. Consistent with the in vitro studies, single agent
      ON123300 caused a dose-dependent suppression of phosphorylation of Akt as well as
      activation of Erk in brain tumors, whereas addition of gefitinib to the ON123300
      regimen significantly enhanced p-Akt inhibition and prevented Erk activation. In
      summary, ON123300 demonstrated favorable pharmacokinetic characteristics, and
      future development for brain tumor therapy would require use of combinations,
      such as gefitinib, that mitigate its Erk activation and enhance its activity.

PMID- 24568971
TI  - Liver cell-specific peptides derived from the preS1 domain of human hepatitis B
      virus.
AB  - The envelope of human hepatitis B virus (HBV) consists of the large (L), middle
      (M), and small (S) surface proteins. The preS1 domain at the N terminus of the L
      protein is essential for recognizing a target cell and for viral infectivity. In
      the present study, peptides derived from the preS1 domain (amino acid residues 2
      19) were synthesized, and their binding affinities for human hepatocellular
      carcinoma (HCC) cells were determined. Non-myristoylated peptides showed much
      lower affinity for HepG2 cells than myristoylated peptides. Although all peptides
      showed significantly higher affinities for two human HCC cell lines (HepG2 and
      HuH-7) compared with other cell lines (HeLa, B16, NMuLi, and NIH 3T3), a modified
      peptide exhibited the highest affinity for HCC cell lines. These results suggest
      that the modified peptide can target liver cells. 

PMID- 24568970
TI  - The role of gene body cytosine modifications in MGMT expression and sensitivity
      to temozolomide.
AB  - The DNA repair protein O(6)-methylguanine-DNA methyltransferase (MGMT) is known
      to play a role in sensitivity to temozolomide. Promoter hypermethylation of MGMT
      is commonly used to predict low expression levels of MGMT in gliomas, despite
      observed discordance between promoter methylation and protein levels. Here, we
      investigated the functional role of gene body cytosine modification in regulating
      levels of MGMT gene expression and sensitivity to temozolomide. In 91 human
      glioblastoma samples, we observed significant variation in MGMT expression levels
      in patients with an unmethylated promoter, with higher levels of gene body
      cytosine modification correlating with higher gene expression levels.
      Furthermore, inducing hypomethylation across the MGMT gene body with decitabine
      corresponded with decreased levels of MGMT gene expression in lymphoblastoid and
      glioblastoma cell lines, indicating an important functional role for gene body
      cytosine modifications in maintaining gene expression. We reasoned that the
      decrease in MGMT expression induced by decitabine may render resistant
      glioblastoma cell lines more sensitive to temozolomide. Consistent with this
      reasoning, we found that the MGMT-expressing glioblastoma cell lines exhibiting
      an unmethylated MGMT promoter that were pretreated with decitabine became
      significantly more sensitive to temozolomide. Overall, our results suggest a
      functional role for gene body cytosine modification in regulating gene expression
      of MGMT and indicate that pretreating patients whose tumors have an unmethylated
      MGMT promoter with decitabine before temozolomide treatment may increase their
      response to therapy.

PMID- 24568973
TI  - ADHD and "eye problems".

PMID- 24568974
TI  - Muscle path length in horizontal strabismus.
AB  - BACKGROUND: Sarcomere adaptation has been proposed as a mechanism for the
      adjustment of rectus muscle length in regulating binocular alignment. The purpose
      of this study was to investigate whether horizontal rectus muscle paths have
      abnormal lengths in subjects with intermittent or alternating strabismus.
      METHODS: High-resolution, surface coil magnetic resonance imaging was obtained in
      2 mm thick axial planes in strabismic patients who had not undergone prior
      surgery and normal control subjects. The lengths of horizontal rectus muscle
      paths were measured digitally in central gaze for the fixating eye only and
      compared. RESULTS: A total of 12 strabismic subjects and 13 controls were
      included: 8 subjects had esotropia averaging 30(Delta), and 4 had exotropia
      averaging 47(Delta). The sample had 80% power to detect muscle path length
      changes of at least the typical surgical doses appropriate to strabismus surgery
      for correction of the mean deviations in each group, had such changes existed.
      Mean (+/- standard deviation) medial rectus path length was 35.0 +/- 4.1 mm in
      controls, not significantly different from 36.3 +/- 1.7 mm in exotropia (P =
      0.56) or 35.8 +/- 2.9 mm in esotropia (P = 0.62). Mean lateral rectus path length
      in controls was 35.7 +/- 4.0 mm, not significantly different from the values of
      39.6 +/- 3.8 mm in exotropia (P = 0.09) and 37.8 +/- 3.3 (P = 0.19) mm in
      esotropia. CONCLUSIONS: Horizontal rectus muscle path lengths are not
      significantly abnormal in commonly encountered intermittent or alternating
      esotropia and exotropia.

PMID- 24568976
TI  - Reproducibility of horizontal extraocular muscle insertion distance in anterior
      segment optical coherence tomography and the effect of head position.
AB  - PURPOSE: To investigate the reproducibility of horizontal extraocular muscle
      insertion distance measurements in anterior segment optical coherence tomography
      (AS-OCT) and to evaluate the effect of eye position on the measurement. METHODS:
      The right eyes of 30 healthy young subjects underwent AS-OCT. Varying eye
      positions were used and the muscle insertion distance was measured by two
      independent examiners who each measured the insertion distance twice. The
      measurement was performed for the lateral rectus and medial rectus muscles with
      the eye rotated 40 degrees , 50 degrees , and 60 degrees  to the midline of the
      instrument. Reproducibility was evaluated with the intraclass correlation
      coefficient (ICC) and Bland-Altman plot. RESULTS: The lateral rectus insertion
      distance was smallest with 50 degrees  rotation and the medial rectus insertion
      distance did not show a consistent pattern in regards to gaze position. The
      differences in insertion distance between different eye positions were not
      statistically significant for both muscles. The inter- and intraexaminer ICC
      reproducibility values were excellent for both lateral and medial rectus
      insertion distance measurements. CONCLUSIONS: Inter- and intraexaminer
      reproducibility were excellent for lateral and medial rectus muscle insertion
      distance measurements using AS-OCT. The measurements tended to be smallest with
      the 50 degrees  position in lateral rectus measurement; however, medial rectus
      measurements were variable.

PMID- 24568975
TI  - Prevalence of attention-deficit/hyperactivity disorder among children with vision
      impairment.
AB  - PURPOSE: To evaluate the prevalence of parent-reported attention
      deficit/hyperactivity disorder (ADHD) in two clinics in Alabama serving children
      with vision impairment. METHODS: The medical records of children 4-17 years of
      age attending the Alabama School for the Blind (ASB) during the 2010-2011 school
      year or seen at the University of Alabama at Birmingham (UAB) Center for Low
      Vision Rehabilitation between 2006 and 2010 were retrospectively reviewed.
      Sociodemographics, ocular characteristics, and parental report of ADHD diagnosis
      were obtained. The prevalence of ADHD was compared to national and state figures
      for age-similar children regardless of comorbidities. The prevalence of ADHD,
      sociodemographic, and ocular characteristics was also compared between clinical
      sites. RESULTS: A total of 264 children participated in the study (95 from ASB
      and 169 from UAB). The prevalence of ADHD among children with visual acuity
      better than hand motion (n = 245) was 22.9%, which is higher than reported state
      (14.3%) and national prevalence (9.5%) for children in this age range. The
      prevalence was similar at ASB (22.4%) and UAB (23.1%). Those with ADHD were
      similar to those without ADHD with respect to age, sex, and race. Children with
      ADHD were significantly less likely to have nystagmus and more likely to have
      better visual acuity (P < 0.05). The prevalence of ADHD among the 19 participants
      with total or near total vision loss (all from ASB) was 10.5%. CONCLUSIONS: Our
      analyses suggest that children with vision impairment may be more likely to be
      diagnosed with ADHD than children in the general population.

PMID- 24568977
TI  - Cyanoacrylate tissue adhesive on a polyglactin scaffold in strabismus surgery: a
      laboratory study.
AB  - BACKGROUND: The use of cyanoacrylate tissue adhesives in strabismus surgery has
      been variously successful, depending primarily on achieving adequate bond
      strength and minimizing extraocular muscle slippage. We investigate a novel
      approach to this problem, involving cyanoacrylate tissue adhesive on a
      polyglactin 910 scaffold as a means to secure extraocular muscle to the sclera
      for strabismus surgery. METHODS: In this experimental laboratory study, butyl
      cyanoacrylate was used to fix a polyglactin 910 scaffold to the sclera of cadaver
      eyes. After allowing for polymerization, a force was applied to the mesh until
      the polyglactin-sclera bond failed. The maximum load (g) required for bond
      failure was recorded. The effects of surface area of the polyglactin 910 mesh as
      well as time required for cyanoacrylate tissue adhesive polymerization on bond
      strength were investigated. RESULTS: All combination of variables tested, except
      for experiments involving polyglactin 910 mesh that is 30 mm(2) with a
      polymerization time of 15 seconds or 30 seconds and polyglactin 910 mesh that is
      40 mm(2) with a polymerization time of 15 seconds, achieved a bond strength that
      was significantly greater than those forces seen in a physiologic setting (P >
      0.05). Increasing area or time resulted in increasing bond strength. Area and
      time were found to be independent variables. CONCLUSIONS: The cyanoacrylate
      tissue adhesive-derived polyglactin-sclera bond achieved a maximum load greater
      than those seen in a physiologic setting. Our novel approach demonstrates a
      clinically feasible alternative to traditional means for bonding muscle to sclera
      in strabismus surgery.

PMID- 24568979
TI  - The long-term outcomes of ocular tics in a pediatric neuro-ophthalmology
      practice.
AB  - PURPOSE: To describe the outcome and comorbidities of ocular tics in children
      evaluated by a pediatric neuro-ophthalmologist. METHODS: The medical records of
      all consecutive patients in a pediatric neuro-ophthalmology practice diagnosed
      with ocular tics (eye rolling, blinking, and widening) were retrospectively
      reviewed. Children with known secondary causes for tics were excluded. Patients,
      parents, and/or guardians were contacted by telephone to obtain follow-up
      information. RESULTS: A total of 43 patients were included in the retrospective
      cohort, with a mean age of 7.8 +/- 4.8 years at diagnosis. Thirty-two patients
      participated in the follow-up survey, with an average follow-up of 6.1 +/- 3.9
      years. None of the 43 children carried a diagnosis of Tourette syndrome or
      obsessive-compulsive disorder (OCD) at presentation; 1 child had attention
      deficit hyperactivity disorder (ADHD). At follow-up, 14 of the 32 children (44%)
      had persistent ocular tics, 3 (9%) reported new nonocular motor tics, 5 (16%)
      reported new vocal tics, and 4 (13%) developed both nonocular motor and vocal
      tics. One patient (3%) was formally diagnosed with Tourette syndrome during the
      follow-up interval, and 3 (9%) were diagnosed with ADHD. CONCLUSIONS: Almost half
      of the children with ocular tics at presentation had persistent ocular tics on
      follow-up. New nonocular motor and vocal tics occurred in several patients.

PMID- 24568980
TI  - Evaluation of an indirect ophthalmoscopy digital photographic system as a
      retinopathy of prematurity screening tool.
AB  - PURPOSE: To determine whether digital retinal images obtained from an indirect
      ophthalmoscopy imaging system (Keeler) can be accurately graded for clinically
      significant retinopathy of prematurity (ROP) by masked experts. METHODS: The
      medical records of infants screened for ROP who had posterior pole images
      acquired using the Keeler system during routine ROP examinations were
      retrospectively reviewed. Two reviewers, masked to patient demographics and
      clinical examination findings, graded the images for: (1) quality (good, fair,
      poor); (2) number of gradable quadrants, from 0 to 4; and (3) posterior pole
      disease (none, pre-plus, plus). The accuracy of grading Keeler images for
      clinically significant ROP (defined as pre-plus or plus disease) was compared to
      results of clinical examination. RESULTS: One eye each of 253 infants was
      included. The mean postmenstrual age at examination was 35 weeks (range, 30-42).
      Grader 1 found the quality of 94% of images to be fair or good; grader 2, 83% of
      images. Grader 1 judged 87% of images to have >=3 gradable quadrants; grader 2,
      77% of images. The sensitivity and specificity of grading pre-plus or worse
      disease on Keeler images were 100% and 86%, respectively, for grader 1, and 94%
      and 89%, respectively, for grader 2. CONCLUSIONS: Digital retinal images obtained
      by the Keeler system can be read with high sensitivity and specificity to screen
      for clinically important ROP. The Keeler system may be a valuable tool for ROP
      screening at remote locations (ie, via telemedicine).

PMID- 24568981
TI  - Comparison of SureSight autorefractor and plusoptiX A09 photoscreener for vision
      screening in rural Honduras.
AB  - PURPOSE: To evaluate the SureSight autorefractor and compare it to the plusoptiX
      A09 photoscreener in the detection of amblyopia risk factors in a cohort of
      Honduran children examined during medical mission work and to assess the utility
      of both devices in the rural setting. METHODS: The medical records of patients
      who had undergone SureSight autorefractor screening, plusoptiX photoscreening,
      and a gold standard pediatric ophthalmology examination, including cycloplegic
      refraction, during a recent medical mission trip to Honduras were retrospectively
      reviewed. RESULTS: A total of 216 children were examined. Of these, 9 (4%) were
      found to have amblyopia risk factors based on the current referral criteria of
      the American Association for Pediatric Ophthalmology and Strabismus on
      ophthalmological examination. The plusoptiX was found to have 89% sensitivity and
      80% specificity; the SureSight, using manufacturer's referral criteria, was found
      to have sensitivity of 89% and specificity of 71%. CONCLUSIONS: Both devices were
      found to be reliable vision screening devices when used on the general population
      of remote villages in Honduras, although the specificity of the plusoptiX A09 was
      higher.

PMID- 24568982
TI  - Repeat Retinomax screening changes positive predictive value.
AB  - PURPOSE: To quantify changes in autorefraction measurement with repeated readings
      using the Retinomax autorefractor and to investigate the clinical implications of
      the results. METHODS: Children referred from a preschool vision screening program
      for a failed autorefraction screening test received repeat autorefraction as well
      as a comprehensive eye examination with cycloplegic retinoscopy at later follow
      up. The intraclass correlation coefficient between initial and follow-up
      autorefraction was calculated to quantify changes in repeated measurements to
      determine whether the second autorefraction significantly changed the predictive
      value that a referred child would meet case definition. Cases were defined by
      AAPOS Vision Screening Committee amblyogenic risk factors under cycloplegic
      retinoscopy. RESULTS: Repeat Retinomax autorefraction had an intraclass
      correlation of 0.70 in the right eye and 0.70 in the left eye for mean sphere. Of
      636 children who were referred on their initial screening, 169 (26.5%) passed a
      repeat screening and this subpopulation had 7 cases (4.1%). Of the 467 (73.5%)
      who again met referral criteria at repeat screening, 268 (57.4%) met case
      definition. The difference in case rates between these subgroups was highly
      significant (Fisher exact test, P < 0.001). CONCLUSIONS: There was clinically
      significant variability when autorefraction measurements were repeated among
      those referred from initial screening, allowing further risk stratification. In
      our study cohort, few children who passed repeat screening required further
      examination. Significant money and overtreatment risk may potentially be avoided
      by rescreening children who are initially referred from screening evaluations and
      only examining those who meet referral criteria after a second screening.

PMID- 24568983
TI  - Factors related to strabismus decompensation after a period of prolonged
      postoperative stability.
AB  - PURPOSE: To identify factors associated with late decompensation of horizontal
      strabismus after a period of prolonged (>12 months) postoperative stability.
      METHODS: Charts from all pediatric horizontal strabismus surgical cases from 1999
      to 2009 were reviewed. Patients with a distance or near alignment of <10(Delta)
      at the first visit >12 months following surgery were included. The primary
      outcome was time from surgery to strabismus decompensation. Multiple variables
      were analyzed using the Cox proportional hazards model. RESULTS: A total of 185
      cases were included. Mean age at surgery was 5.1 years and mean follow-up was
      62.2 months. Late decompensation rate was 31%; of these, 54% underwent
      reoperation. Using two different models, a higher risk of decompensation was
      associated with both the presence of preoperative oblique dysfunction (P =
      0.023/0.002) and larger distance/near deviations at the first >12 months
      postoperative visit (P = 0.033/0.012). CONCLUSIONS: Worsening of alignment >12
      months after horizontal strabismus surgery occurs in almost one-third of
      patients. Preoperative oblique dysfunction is associated with long-term
      instability, possibly because it is a surrogate for sensory torsion and poor
      fusion. Additionally, larger distance and near deviations at >12 months after
      surgery were each associated with late decompensation. The rate of decompensation
      for patients with deviations of 0(Delta) to <4(Delta) was less than those with
      deviations of 4(Delta) to <8(Delta) and >8(Delta), suggesting that the biologic
      behavior of all deviations within the monofixation range (0(Delta) to 8(Delta))
      is not uniform.

PMID- 24568984
TI  - Trochlea surgery for acquired Brown syndrome.
AB  - PURPOSE: To describe surgical treatment of acquired Brown syndrome by trochlea
      reconstruction and trochlea adhesiotomy. METHODS: The medical records of patients
      with acquired Brown syndrome who underwent intraoperative forced duction testing
      under direct view of the trochlea from 2010 to 2012 were retrospectively
      reviewed. In all cases, the site of restricted movement was identified, after
      which either the trochlea was reconstructed or the trochlear adhesion was
      removed. Surgical results were assessed by means of the pre- and postoperative
      Hess chart scores and binocular single vision test scores. RESULTS: Six eyes of 6
      patients were included. In 4 patients the trochlea was reconstructed; in 2, the
      adhesion was removed. A significant improvement in the Hess chart scores was
      observed postoperatively in 5 of the 6 patients (P = 0.047). Binocular single
      vision test scores also significantly improved in 4 of 5 patients (P = 0.019). No
      iatrogenic superior oblique muscle paresis was observed in any of the patients.
      CONCLUSIONS: Our technique of isolating the source of limitation of elevation and
      treating with trochlea reconstruction or adhesion removal successfully treated
      acquired Brown syndrome in these patients.

PMID- 24568985
TI  - Uveal melanoma among Finnish children and young adults.
AB  - PURPOSE: To characterize uveal melanoma (UM) among children and young adults in a
      high-risk region for this cancer. METHODS: The medical records of consecutive
      patients <25 years of age with UM treated from 1962 to 2009 were retrospectively
      reviewed. The following data were collected: sex, tumor location and size, tumor
      node metastasis (TNM) stage, vision, and survival. We compared data with five
      previous series reporting 70 matching patients and combined them for meta
      analysis of survival. RESULTS: Of 1,185 UM patients, 18 were eligible. UM
      frequency in patients <25 years of age was 1.3%; in those <=20 years of age,
      0.6%. Median follow-up time was longer than in the previous series combined (11.6
      vs 5.4 years). Females outnumbered males 2:1. Median tumor thickness was higher
      in our series (8 vs 5 mm) and increased with age. Median tumor diameter was
      similar to previous series (12 mm). Of our patients, 83% were stage II; 17%,
      stage III. In previous series, 26% were stage I; 64%, stage II; and 10%, stage
      III. Survival was 76% at 5 and 10 years, compared to 98% in previous series. By
      meta-analysis, mortality increased with stage, age > 17 years, female sex, and if
      the ciliary body was involved. CONCLUSIONS: Tumor stage was higher than in other
      regions. Age >17 years, female sex, and tumor stage adversely influenced survival
      among patients <25 years of age with UM.

PMID- 24568987
TI  - Cross-sectional study on childhood cerebral visual impairment in New Zealand.
AB  - PURPOSE: To determine the prevalence, etiology, and avoidable causes of childhood
      cerebral visual impairment (CVI) in New Zealand. METHODS: The clinical and
      educational records of blind and low vision children enrolled in the Blind and
      Low Vision Education Network, New Zealand (BLENNZ), a national referral center,
      were retrospectively analyzed. The WHO Program for Prevention of Blindness
      (WHO/PBL) Eye Examination Record for Children with Blindness and Low Vision was
      used to record data from children <=16 years of age diagnosed with CVI and visual
      acuity <=6/18 enrolled with BLENNZ. Data analyzed included demographics,
      etiology, visual acuity, visual fields, educational setting, and rehabilitation
      plan. RESULTS: A total of 182 children (blind, 143; low vision, 39) were
      included. The calculated prevalence of childhood CVI in New Zealand was 0.02%. Of
      these, only 21% required low vision aids. Principle causes of CVI blindness were
      perinatal hypoxia/asphyxia (25%), nonaccidental injury (7%), and prematurity
      (7%). Approximately 50% of all cases of CVI blindness were potentially avoidable;
      of these, 52% were caused by perinatal hypoxia and 14% by nonaccidental injury.
      CONCLUSIONS: The conservative calculated prevalence of CVI, responsible for 30%
      of all childhood blindness in New Zealand, was 0.02%. The most common cause of
      CVI blindness in New Zealand, perinatal asphyxia, is also an avoidable cause.

PMID- 24568986
TI  - Clinical and cost impact of a pediatric cataract follow-up program in western
      Nepal and adjacent northern Indian States.
AB  - BACKGROUND: High-quality, comprehensive pediatric cataract surgery programs have
      recently developed in low-income countries, but postoperative care has lagged.
      This study evaluated the post-cataract surgery follow-up program implemented in
      March 2011 at the Lumbini Eye Institute in Bhairahawa, Nepal, which included a
      full-time pediatric counselor and program director, a specific database, a
      tracking system, and cell phone reminders. METHODS: Baseline data for all
      cataract surgical patients <16 years of age were obtained retrospectively from
      hospital administrative records for 2009, the year prior to program introduction,
      and prospectively for all cases between March 1, 2011, and February 28, 2012. The
      statistical significance of the difference in the proportion of children
      attending follow-up in 2009 versus 2011-12 was calculated, and the overall
      program costs for 2011-12 was determined based on hospital records. RESULTS: In
      2011-12, 334 children (248 males [74%]) underwent cataract surgery, including 89
      Nepali (27%) and 245 Indian (73%) children. The proportion of boys was
      significantly higher in 2011-12 compared to 2009, but there were no differences
      in terms of age or distance to hospital. In 2009, 87%, 60%, and 37% attended
      their first, second, and third follow-up visits, respectively. Follow-up rates
      improved significantly to 96%, 81%, and 57%, respectively, after the
      implementation of the postoperative follow-up program. The 2011-12 program is
      estimated to have cost US$17,444. CONCLUSIONS: The new post-cataract surgery
      program resulted in improved follow-up at relatively little additional cost.

PMID- 24568989
TI  - Accommodative esotropia decompensated to cyclic esotropia in a 6-year-old boy.
AB  - Cyclic esotropia, characterized by alternating intervals of esotropia and
      orthotropia, is associated with decreased vision, trauma, strabismus surgery, or
      central nervous system disease. We report a 6-year-old boy who developed cyclic
      esotropia after 3 years of successful control of accommodative esotropia with
      full hyperopic correction. After bilateral medial rectus recession, he remained
      esophoric with good binocular function and stereoacuity. To our knowledge, this
      is the first report of accommodative esotropia decompensating into a cyclic
      esotropia. 

PMID- 24568988
TI  - Isolated abducens nerve palsy following neonatal hepatitis B vaccination.
AB  - We report a case of sudden-onset abducens nerve palsy in an otherwise healthy 8
      day-old boy following neonatal hepatitis B vaccination. A complete workup,
      including magnetic resonance imaging of the brain and orbits revealed no
      abnormalities. The patient recovered fully, with no recurrence of the abducens
      nerve palsy despite receiving the full course of the hepatitis B vaccine as well
      as other recommended immunizations through 18 months of age. We review the
      literature regarding vaccination-induced abducens nerve palsy and discuss the
      possible mechanisms of injury. 

PMID- 24568990
TI  - Intravitreal foscarnet for recurring CMV retinitis in a congenitally infected
      premature infant.
AB  - A girl born at 32 weeks' gestational age was diagnosed at birth with congenital
      cytomegalovirus (CMV) infection without ocular involvement. On day 19 of life,
      retinal examination requested for retinopathy of prematurity (ROP) identified
      bilateral CMV retinitis and stage 1 ROP. Treatment of macular threatening CMV
      infection with intravitreal foscarnet injections and intravenous ganciclovir for
      6 weeks led to quiescence of retinitis. Bilateral recurrence of CMV retinitis
      occurred on day 89 of life, requiring a second course of intravitreal foscarnet
      injections and intravenous ganciclovir. Both the initial presentation and
      reactivation of CMV retinitis were identified on examination for ROP and would
      have gone unrecognized had the infant not met ROP screening criteria. This case
      demonstrates delayed presentation of CMV retinitis after initial negative retinal
      examination in a premature infant with congenital infection and concurrent ROP. 

PMID- 24568991
TI  - Beta blocker treatment of infantile conjunctival hemangiomas--observations from 2
      cases.
AB  - Infantile conjunctival hemangiomas are rare lesions in comparison to cutaneous
      and orbital capillary hemangiomas. They generally present several weeks following
      birth as a red stromal mass. Recent reports of cutaneous and orbital infantile
      hemangiomas involuting in response to oral or topical beta blocker treatment
      suggest that infantile conjunctival hemangiomas could respond similarly. We
      report 2 cases of presumed infantile hemangiomas of the conjunctiva. One,
      associated with cutaneous hemangiomas, did not respond to oral propranolol; the
      other was isolated and resolved with topical timolol. 

PMID- 24568992
TI  - Orbital cellulitis and intraconal abscess formation after strabismus surgery in
      an adult patient.
AB  - We report a 60-year-old woman who presented with orbital cellulitis, restricted
      ocular motility, proptosis, and visual acuity of counting fingers in her left eye
      3 days after strabismus surgery. Although she initially responded well to
      antibiotic and anti-inflammatory therapy, visual acuity in the left eye again
      decreased on postoperative day 5. Radiographic imaging revealed an intraconal
      orbital abscess, and she underwent left lateral orbitotomy with abscess drainage,
      with continued antibiotics and a tapering dose of steroids. To our knowledge,
      this is the first case of orbital cellulitis and intraconal abscess after
      strabismus surgery in an adult.

PMID- 24568993
TI  - Strabismus surgery in patients receiving warfarin anticoagulation.
AB  - Many ophthalmologists consider switching patients on chronic warfarin
      anticoagulation to enoxaparin or discontinuing their anticoagulant for strabismus
      surgery. We report 3 successful cases of strabismus surgery on patients taking
      warfarin. No excessive bleeding was encountered intraoperatively or during the
      recovery period. To our knowledge, this is the first report regarding the safety
      of strabismus surgery in patients who are maintained on warfarin during
      strabismus surgery. 

PMID- 24568978
TI  - Office probing for treatment of nasolacrimal duct obstruction in infants.
AB  - PURPOSE: To determine whether demographic or clinical factors are associated with
      the outcome of office-based nasolacrimal duct probing for the treatment of
      congenital nasolacrimal duct obstruction (NLDO). METHODS: In two multicenter
      prospective studies, 384 eyes of 304 children aged 6 to <15 months with NLDO
      underwent a nasolacrimal duct probing performed in the office using topical
      anesthesia. Treatment success, defined as no clinical signs of NLDO (epiphora,
      increased tear lake, or mucous discharge) and no reoperation, was assessed 1
      month after probing in one study and 6 months after probing in the other study.
      Data from both studies were pooled to evaluate associations between baseline
      characteristics and treatment success. RESULTS: Office probing was successful in
      75% of eyes overall (95% CI, 70%-80%). The procedure was less successful in eyes
      of children with bilateral NLDO compared with unilateral NLDO (63% vs 80%;
      relative risk = 0.78 [95% CI, 0.66-0.92]) and in eyes that had 2 or 3 clinical
      signs of NLDO compared with one (71% vs 83%; relative risk = 0.88 [95% CI, 0.81
      0.96]). Treatment success did not appear to be related to age, specific clinical
      signs of NLDO, prior treatment, or research study. CONCLUSIONS: Performing
      nasolacrimal duct probing in the office successfully treats NLDO in the majority
      of cases in children aged 6 to <15 months. The success rate is lower with
      bilateral disease or when more than one clinical sign of NLDO is present.

PMID- 24568994
TI  - Coats disease in a 3-week-old boy.
AB  - Coats disease is a rare, idiopathic retinal vasculopathy that predominantly
      affects males in the first decade of life. We report the case of a 3-week-old boy
      who presented with atypical rapidly progressing disease suggestive of Coats
      exudative vasculopathy. The eye developed retinal fibrosis and phthisis bulbi
      within 4 weeks. Retinoblastoma could not be ruled out, although histopathology
      after enucleation revealed no retinoblastoma. To our knowledge, this is the
      youngest case of Coats disease to be reported in the literature. This case
      highlights the wide variation in the clinical presentation of Coats disease and
      the difficulty in differentiating it from diffuse infiltrative retinoblastoma. 

PMID- 24568995
TI  - Bilateral canalicular and nasolacrimal duct obstruction in congenital erosive and
      vesicular dermatosis: a case report and review of the literature.
AB  - We report the ocular findings in a 2.5-year-old girl with a history of congenital
      erosive and vesicular dermatosis at birth. We highlight the complexity of the
      associated nasolacrimal duct obstruction with canalicular scarring and review the
      ocular manifestations of this rare disease. 

PMID- 24568996
TI  - Multisegment coloboma in a case of Marfan syndrome: another possible effect of
      increased TGFbeta signaling.
AB  - Colobomata are etiologically heterogeneous and may occur as an isolated defect or
      as a feature of a variety of single-gene disorders, chromosomal syndromes, or
      malformation syndromes. Although not classically associated with Marfan syndrome,
      colobomata have been described in several reports of Marfan syndrome, typically
      involving the lens and rarely involving other ocular structures. While colobomata
      of the lens have been described in Marfan syndrome, there are very few reports of
      coloboma involving other ocular structures. We report a newborn boy presenting
      with coloboma of the iris, lens, retina, and optic disk who was subsequently
      diagnosed with Marfan syndrome. Marfan syndrome is a disorder of increased
      TGFbeta signaling, and recent work in the mouse model suggests a role for TGFbeta
      signaling in eye development and coloboma formation, suggesting a causal
      association between Marfan syndrome and coloboma. 

PMID- 24568997
TI  - Optical coherence tomography characteristics of epi-iridic membrane in a child
      with recurrent hyphema and presumed juvenile xanthogranuloma.
AB  - We report a case of spontaneous hyphema in a 6-month-old girl with no history of
      trauma and no visible iris mass. Subtle green-blue heterochromia was noted in the
      right eye. The iris crypts in the right eye appeared flattened by a thin,
      transparent layer on the iris surface. Anterior segment optical coherence
      tomography (AS-OCT) disclosed a thin homogenous membrane overlying the entire
      iris surface in the right eye. Fluorescein angiography revealed diffuse
      hyperfluorescence without neovascularization. These features were suggestive of
      diffuse iris juvenile xanthogranuloma. Sub-Tenon's triamcinolone acetate plus
      topical corticosteroids eyedrops resolved the condition within 1 month. 

PMID- 24568998
TI  - Vision-related quality of life in children with glaucoma.
AB  - Although reporting vision-related quality of life (VRQoL) outcomes has become
      increasingly common in adult glaucoma studies, little is known about the
      influence of disease severity, medication burden, and surgical experience on the
      quality of life of children with glaucoma. We tested the feasibility of
      administering a self-reported VRQoL instrument and describe the VRQoL in children
      with glaucoma. Better VRQoL was correlated with higher visual acuity in the
      better-seeing eye but not the number of surgeries the child had undergone or the
      number of prescribed eyedrops. 

PMID- 24568999
TI  - Visualization of the meibomian glands by means of noncontact mobile-type
      meibography (Meibopen) in a 16-year-old girl with unilateral marginal
      staphylococcal keratitis.
AB  - Marked alterations of the meibomian glands in a patient with marginal
      staphylococcal keratitis can be seen using the noncontact mobile-type meibography
      system, a simple and convenient tool that facilitates visualization of meibomian
      glands throughout the entire upper and lower eyelids. 

PMID- 24569000
TI  - Magnetic prism alignment system for measuring large-angle strabismus.
AB  - Prismatic measurement of large-angle strabismus requires the simultaneous use of
      two or more prisms for neutralization. To facilitate the clinical measurement of
      large-angle strabismus a new prism system was designed utilizing a flat plate and
      a ferrous metal surface coupled with prisms containing rare earth magnets
      implanted in their base and bottom surfaces. 

PMID- 24569001
TI  - Cumulative inequality and racial disparities in health: private insurance
      coverage and black/white differences in functional limitations.
AB  - OBJECTIVES: To test different forms of private insurance coverage as mediators
      for racial disparities in onset, persistent level, and acceleration of functional
      limitations among Medicare age-eligible Americans. METHOD: Data come from 7 waves
      of the Health and Retirement Study (1996-2008). Onset and progression latent
      growth models were used to estimate racial differences in onset, level, and
      growth of functional limitations among a sample of 5,755 people aged 65 and older
      in 1996. Employer-provided insurance, spousal insurance, and market insurance
      were next added to the model to test how differences in private insurance
      mediated the racial gap in physical limitations. RESULTS: In baseline models,
      African Americans had larger persistent level of limitations over time. Although
      employer-provided, spousal provided, and market insurances were directly
      associated with lower persistent levels of limitation, only differences in market
      insurance accounted for the racial disparities in persistent level of
      limitations. DISCUSSION: Results suggest private insurance is important for
      reducing functional limitations, but market insurance is an important mediator of
      the persistently larger level of limitations observed among African Americans.

PMID- 24569002
TI  - Aging and subjective well-being in later life.
AB  - OBJECTIVES: This paper examines age-related changes in subjective well-being
      (SWB) in later life using multiple measures that cover eudemonic, evaluative, and
      affective dimensions of well-being. METHOD: Using data from 5 waves of
      respondents aged 50 and older from the English Longitudinal Study of Ageing (2002
      11), we fit multilevel linear growth curve models to examine the cohort
      differences and individual aging effects on quality of life, depressive
      symptomatology, and life satisfaction. RESULTS: Older cohorts are shown to have
      equivalent or better SWB than younger cohorts for each well-being measure.
      Nonetheless, individual aging effects for each well-being measure were observed
      with deterioration in well-being being greatest in older cohorts, even when
      adjusting for age-related changes in later life, including widowhood, retirement,
      and declining health. DISCUSSION: The results suggest that although older cohorts
      enjoy higher levels of SWB than their younger counterparts when under similar
      circumstances, they experience sharper declines, especially in the very oldest
      cohorts. The findings demonstrate the importance of separating out cohort
      differences and aging effects and also of taking into account the
      multidimensionality of SWB to determine the point at which age deterioration
      begins to occur across different measures.

PMID- 24569004
TI  - Oral anticoagulant treatment in geriatric patients with nonvalvular atrial
      fibrillation in the era of direct oral anticoagulant agents.

PMID- 24569005
TI  - Central venous catheter insertion in peripheral blood hematopoietic stem cell
      sibling donors: the SIdEM (Italian Society of Hemapheresis and Cell Manipulation)
      point of view.
AB  - Collection of peripheral blood hematopoietic stem cells (PBSC) is the practice of
      choice for graft procurement in both autologous and allogeneic setting. The
      success of this procedure depends on the use of adequate vascular accesses. Well
      sized peripheral veins are the first option in autologous and allogeneic
      donations. In autologous setting, in case of lack of adequate veins, central
      venous catheters (CVC) may be used for collection. In the allogeneic setting,
      although available data have shown the safety of the use of CVC, there are still
      some controversies about the possible insertion of a CVC in donors. A specific
      policy from competent registries is usually applied in the different countries to
      regulate the use of CVC in unrelated donors. In siblings, the question is still
      undefined due both to the lack of shared guidelines and to the specific
      characteristics of this donation. In fact, in not so rare cases, larger stem cell
      doses for specific cell manipulations (e.g., T/B cell depletion in the
      haploidentical setting) are needed. The lack of international rules or standard
      that forbid the use of a CVC in siblings and published data that document the
      safety of this procedure, allowed the Societa Italiana di Emaferesi e
      Manipolazione Cellulare (SIdEM) national Board to identify a possible, shared,
      operational approach to address this issue by a case-specific risk-benefit
      assessment. 

PMID- 24569003
TI  - The relationship between major depression and nonsuicide mortality for U.S.
      adults: the importance of health behaviors.
AB  - OBJECTIVES: We aim to elucidate the role of health behaviors and health
      conditions in the association between depression and mortality. First, we examine
      the relationship between major depression and nonsuicide mortality among U.S.
      adults aged 50 and older. Second, we examine the relationship between major
      depression and cardiovascular disease and cancer, by baseline disease status.
      Third, we examine the role of health behaviors as potential mediators of the
      association between major depression and cause-specific mortality. METHODS: We
      use data from the 1999 National Health Interview Study linked to the 2006
      National Death Index (N = 11,369; M age = 65, deaths = 2,162) and Cox
      proportional hazards models to describe the relationships among major depression,
      health behaviors (alcohol use, cigarette smoking, physical activity), and
      nonsuicide mortality. We examine cause-specific mortality (cardiovascular and
      cancer) by baseline disease status. RESULTS: Major depression remains associated
      with a 43% increase in the risk of death over the follow-up period, after we
      account for sociodemographic characteristics, health behaviors, and health
      conditions. Major depression is associated with 2.68 times the risk of
      cardiovascular disease mortality among those who did not have cardiovascular
      disease at baseline and 1.82 times for those with baseline cardiovascular
      disease. Health behaviors reduce the hazard ratio by 17% for all nonsuicide
      mortality, 3% for cardiovascular disease mortality, and 12% for cancer mortality.
      DISCUSSION: Our results provide evidence of the important role of health
      behaviors and health conditions in the depression-mortality relationship and
      highlight the importance of identifying risk factors for depression among aging
      adults.

PMID- 24569007
TI  - Analysis of arson fire debris by low temperature dynamic headspace adsorption
      porous layer open tubular columns.
AB  - In this paper we present results of the application of PLOT-cryoadsorption (PLOT
      cryo) to the analysis of ignitable liquids in fire debris. We tested ignitable
      liquids, broadly divided into fuels and solvents (although the majority of the
      results presented here were obtained with gasoline and diesel fuel) on three
      substrates: Douglas fir, oak plywood and Nylon carpet. We determined that PLOT
      cryo allows the analyst to distinguish all of the ignitable liquids tested by use
      of a very rapid sampling protocol, and performs better (more recovered
      components, higher efficiency, lower elution solvent volumes) than a conventional
      purge and trap method. We also tested the effect of latency (the time period
      between applying the ignitable liquid and ignition), and we tested a variety of
      sampling times and a variety of PLOT capillary lengths. Reliable results can be
      obtained with sampling time periods as short as 3min, and on PLOT capillaries as
      short as 20cm. The variability of separate samples was also assessed, a study
      made possible by the high throughput nature of the PLOT-cryo method. We also
      determined that the method performs better than the conventional carbon strip
      method that is commonly used in fire debris analysis. 

PMID- 24569006
TI  - Fabrication of metal-organic framework MIL-88B films on stainless steel fibers
      for solid-phase microextraction of polychlorinated biphenyls.
AB  - Metal-organic frameworks (MOFs) have received considerable attention as novel
      sorbents for sample preparation due to their fascinating structures and
      functionalities such as large surface area, good thermal stability, and uniform
      structured nanoscale cavities. Here, we report the application of a thermal and
      solvent stable MOF MIL-88B with nanosized bipyramidal cages and large surface
      area for solid-phase microextraction (SPME) of polychlorinated biphenyls (PCBs).
      Novel MIL-88B coated fiber was fabricated via an in situ hydrothermal growth of
      MIL-88B film on etched stainless steel fiber. The MIL-88B coated fiber gave large
      enhancement factors (757-2243), low detection limits (0.45-1.32ngL(-1)), and good
      linearity (5-200ngL(-1)) for PCBs. The relative standard deviation (RSD) for six
      replicate extractions of PCBs at 100ngL(-1) on MIL-88B coated fiber ranged from
      4.2% to 8.7%. The recoveries for spiked PCBs (10ngL(-1)) in water and soil
      samples were in the range of 79.7-103.2%. Besides, the MIL-88B coated fiber was
      stable enough for 150 extraction cycles without significant loss of extraction
      efficiency. The developed method was successfully applied to the determination of
      PCBs in water samples and soil samples. 

PMID- 24569008
TI  - Correlation of chromatographic performance with morphological features of organic
      polymer monoliths.
AB  - Monoliths are considered to be a low pressure alternative to particle packed
      columns for liquid chromatography (LC). However, the chromatographic performance
      of organic monoliths, in particular, has still not reached the level of particle
      packed columns. Since chromatographic performance can be attributed to
      morphological features of the monoliths, in-situ characterization of the monolith
      structure in three dimensions would provide valuable information that could be
      used to help improve performance. In this work, serial sectioning and imaging
      were performed with a dual-beam scanning electron microscope for reconstruction
      and quantitative characterization of poly(ethylene glycol) diacrylate (PEGDA)
      monoliths inside a capillary column. Chord lengths, homogeneity factors,
      porosities and tortuosities were calculated from three-dimensional (3D)
      reconstructions of two PEGDA monoliths. Chromatographic efficiency was better for
      the monolith with smaller mean chord length (i.e., 5.23MUm), porosity (i.e.,
      0.49) and tortuosity (i.e., 1.50) compared to values of 5.90MUm, 0.59 and 2.34,
      respectively, for the other monolithic column. Computational prediction of
      tortuosity (2.32) was found to be in agreement with the experimentally measured
      value (2.34) for the same column. The monoliths were found to have significant
      radial heterogeneity since the homogeneity factor decreased from 5.39 to 4.89
      (from center to edge) along the column radius. 

PMID- 24569009
TI  - The role of the laterodorsal tegmental nucleus in methamphetamine conditioned
      place preference and locomotor activity.
AB  - Methamphetamine (METH) indirectly stimulates the laterodorsal tegmental nucleus
      (LDT) acetylcholine (ACh) neurons to increase ACh within the ventral tegmental
      area (VTA). LDT ACh inhibition attenuates METH and saline locomotor activity. The
      aim of these experiments was to determine whether LDT ACh contributes to METH
      conditioned place preference (CPP). C57BL/6J mice received a bilateral
      electrolytic or sham lesion of the LDT. After recovery, mice received alternating
      pairings of METH (0.5 mg/kg) and saline with distinct tactile floor cues over 8
      days. During preference tests, mice were given access to both floor types and
      time spent on each was recorded. Mice were tested again after exposure to both
      extinction and reconditioning trials. Brains were then processed for choline
      acetyltransferase immunohistochemistry to label LDT ACh neurons. Lesioned mice
      had significantly fewer LDT ACh neurons and showed increased saline and METH
      locomotor activity during the first conditioning trial compared to sham mice.
      Locomotor activity (saline and METH) was negatively correlated with the number of
      LDT ACh neurons. Lesioned and sham mice showed similar METH CPP following
      conditioning, extinction and reconditioning trials. LDT ACh neurons are not
      necessary for METH reward as indexed by CPP, but may be important for basal and
      METH-induced locomotor activity.

PMID- 24569011
TI  - Transient inactivation of the pigeon hippocampus or the nidopallium caudolaterale
      during extinction learning impairs extinction retrieval in an appetitive
      conditioning paradigm.
AB  - The majority of experiments exploring context-dependent extinction learning
      employ Pavlovian fear conditioning in rodents. Since mechanisms of appetitive and
      aversive learning are known to differ at the neuronal level, we sought to
      investigate extinction learning in an appetitive setting. Working with pigeons,
      we established a within-subject ABA renewal paradigm based on Rescorla (Q J Exp
      Psychol 61:1793) and combined it with pharmacological interventions during
      extinction. From the fear conditioning literature, it is known that both
      prefrontal cortex and the hippocampus are core structures for context-specific
      extinction learning. Accordingly, we transiently inactivated the nidopallium
      caudolaterale (NCL, a functional analogue of mammalian prefrontal cortex) and the
      hippocampus in separate experiments by intracranial infusion of the sodium
      channel blocker tetrodotoxin immediately before extinction training. We find that
      TTX in both structures non-specifically suppresses conditioned responding, as
      revealed by a reduction of response rate to both the extinguished conditioned
      stimulus and a control stimulus which remained reinforced throughout the
      experiment. Furthermore, TTX during extinction training impaired later extinction
      retrieval assessed under drug-free conditions. This was true when responding to
      the extinguished stimulus was assessed in the context of extinction but not when
      tested in the context of acquisition, although both contexts were matched with
      respect to their history of conditioning. These results indicate that both NCL
      and hippocampus are involved in extinction learning under appetitive conditions
      or, more specifically, in the consolidation of extinction memory, and that their
      contribution to extinction is context-specific. 

PMID- 24569010
TI  - Early enriched environment induces an increased conversion of proBDNF to BDNF in
      the adult rat's hippocampus.
AB  - An enriched environment has been shown to influence brain plasticity and function
      by involving the action of brain-derived neurotrophic factor (BDNF). BDNF, which
      is synthesized as a precursor molecule (proBDNF) that undergoes proteolytic
      cleavage, plays an important role in synaptic plasticity and contributes to
      several brain functions such as memory, learning, and behavior. The neurotrophins
      and proneurotrophins often play opposite roles in the brain, suggesting that
      proteolytic cleavage of proneurotrophins controls the action of neurotrophins.
      However, few studies have focused on the expression and cleavage of proBDNF after
      exposure to an enriched environment. Our study aimed to explore the effects of an
      early-enriched environment on the conversion of proBDNF to BDNF in the adult
      rats' hippocampus. We found that there was no difference in the expression of
      proBDNF in the hippocampus between the SE (standard environment) and EE (enriched
      environment) rats, but a significantly increased BDNF protein level was found in
      the EE rats. Thus, a remarkably enhanced ratio of BDNF to proBDNF (BDNF/proBDNF)
      was observed in the EE rats. In addition, the EE resulted in a remarkably up
      regulated matrix metalloproteinase-9 (MMP-9) in the hippocampus, which played a
      key role in converting proBDNF to BDNF in the extracellular space. Furthermore,
      the expression of synapse-related proteins (NR1 and NR2A) was analyzed, and the
      results indicated that EE could significantly increase the expression of NR1 and
      NR2A in the hippocampus. In addition, the behavioral results showed that EE
      reduced anxiety-like behavior in the elevated-plus maze test and reduced
      immobility time in the forced swimming test. Moreover, the EE resulted in an
      increased preference for sucrose compared to the SE. These results suggested that
      the EE up-regulated MMP-9 levels within the hippocampus, which might facilitate
      the conversion of proBDNF to BDNF, thereby contributing to the long lasting
      alterations of synaptic plasticity and behavior. 

PMID- 24569012
TI  - Theta activity in local field potential of the ventral tegmental area in sleeping
      and waking rats.
AB  - Hippocampal theta rhythm appears in two vigilance states: active waking and
      paradoxical sleep. The ventral tegmental area (VTA) is active in sleep and waking
      and is connected to the hippocampus. We assessed the relationship between local
      field potential (LFP) of the VTA and sleep-waking stages in freely moving rats.
      Electrical activity of the VTA was divided into: quiet waking (W), waking with
      theta (WT), slow wave sleep (SWS) and paradoxical sleep (PS), depending on the
      hippocampal signal and the animal's behavior. We analyzed total power in the VTA
      signal and we also extracted peak power (Pmax) and corresponding frequency (Fmax)
      in theta and delta bands from both the VTA and hippocampal recording. In the VTA
      the 6-9 Hz band had the highest power during PS, and the ratio of the 6-9 to 3-6
      Hz power was highest during both PS and WT, which accentuated Pmax of this
      particular theta sub-band. During W, a very slight increase (or plateau) in
      signal power was seen in theta range. Pmax and Fmax of theta were higher in PS
      than in both WT and W, and these parameters did not differ between W and WT.
      During WT and PS, Fmax in the 6-9 Hz band was greatly correlated between the VTA
      and hippocampus signal. We also detected high cross-correlation in power spectra
      between the hippocampus and the VTA (for delta and theta, during WT and PS). The
      results suggest that the VTA may belong to the broad network involved in theta
      rhythm induction.

PMID- 24569013
TI  - Large neurotoxic amygdala lesion impairs reinforcement omission effects.
AB  - The amygdala has been implicated in a variety of motivational and attentional
      functions related to appetitive learning. Some studies showed that electrolytic
      lesions of the amygdaloid complex disrupted reinforcement omission effects
      (ROEs). However, recent studies that investigated ROEs employing neurotoxic
      lesions in specific amygdala areas - the central nucleus (CeA) or basolateral
      complex (BLA) of the amygdala - showed that CeA lesions or BLA lesions can
      interfere with, but do not eliminate ROEs. Although the effects of neurotoxic
      lesions in particular areas of the amygdala differed from those of a large gross
      lesion, these studies have indicated that it is possible that the amygdala is
      involved in ROE modulation. Furthermore, the effect that a neurotoxic lesion
      involving both areas (CeA and BLA) has on ROEs remains unexplored. Thus, the
      present study aimed to clarify whether the functional impairment related to large
      amygdala activation affects ROEs, in a neurotoxic lesion procedure. If this is
      the case, the underlying process may contribute to a better understanding of the
      involvement of the amygdala in ROEs modulation. After acquisition of stable
      performance during pre-lesion training in which rats were trained to respond on a
      fixed-interval 6 s with limited hold 6 s schedules (FI 6 s LH 6 s), lesions were
      made including both the CeA and BLA areas. In test sessions, the partial omission
      of reinforcement was introduced. The results showed that bilateral lesion of both
      CeA and BLA impaired ROEs, suggesting that amygdala is part of ROEs' modulation
      circuitry.

PMID- 24569014
TI  - Drug-induced suppression of ACTH secretion does not promote anti-depressive or
      anxiolytic effects.
AB  - Mammals respond to a real or perceived stress in an integrated physiological and
      psychological fashion. Psychiatric disorders like major depression and anxiety
      have been associated to stressful events. In a previous study we demonstrated
      that the stress-induced ACTH secretion can be robustly inhibited by the
      concurrent use of CRF1 (CP154,526 - Pfizer) and V1B (SSR149415 - Sanofi-Aventis)
      non-peptide antagonists. A proof of mechanism was offered by substituting
      CP154,526 by SSR125543 and obtaining the same results on three stress models:
      forced swimming, ether vapor inhalation and restraint. SSR125543 effectively
      blocked only restraint stress-induced ACTH secretion. We then challenged the
      hypothesis that the concurrent use of both antagonists would have a potent effect
      on behavioral models of anxiety and depression. Decreasing doses (30-0.1 mg/kg
      s.c.) of both drugs were tested in three behavioral models: Porsolt forced
      swimming test, elevated plus maze and social interaction. Results showed that
      these drugs had no effect on anxiety models (plus maze and social interaction)
      but significantly reduced immobility time in the forced swimming test, suggesting
      anti-depressive action in a dose-range from 1 to 30 mg/kg, not different from the
      reported in the literature referring to one drug or the other. This negates the
      proposed hypothesis of summation/potentiation of effects as observed in stress
      induced ACTH secretion. These results point toward the involvement of extra
      hypothalamic sites for the anti-depressive effects. Recent Phase II clinical
      research on anti-depressive effects of these drugs has failed rising strong
      criticisms against the predictive value of behavioral tests currently employed.

PMID- 24569015
TI  - Sequencing and comparison of the mitochondrial COI gene from isolates of
      Arbuscular Mycorrhizal Fungi belonging to Gigasporaceae and Glomeraceae families.
AB  - Arbuscular Mycorrhizal Fungi (AMF) are well known for their ecological importance
      and their positive influence on plants. The genetics and phylogeny of this group
      of fungi have long been debated. Nuclear markers are the main tools used for
      phylogenetic analyses, but they have sometimes proved difficult to use because of
      their extreme variability. Therefore, the attention of researchers has been
      moving towards other genomic markers, in particular those from the mitochondrial
      DNA. In this study, 46 sequences of different AMF isolates belonging to two main
      clades Gigasporaceae and Glomeraceae have been obtained from the mitochondrial
      gene coding for the Cytochrome c Oxidase I (COI), representing the largest
      dataset to date of AMF COI sequences. A very low level of divergence was recorded
      in the COI sequences from the Gigasporaceae, which could reflect either a slow
      rate of evolution or a more recent evolutionary divergence of this group. On the
      other hand, the COI sequence divergence between Gigasporaceae and Glomeraceae was
      high, with synonymous divergence reaching saturated levels. This work also showed
      the difficulty in developing valuable mitochondrial markers able to effectively
      distinguish all Glomeromycota species, especially those belonging to
      Gigasporaceae, yet it represents a first step towards the development of a full
      mtDNA-based dataset which can be used for further phylogenetic investigations of
      this fungal phylum. 

PMID- 24569016
TI  - First molecular phylogeny of the circumtropical bivalve family Pinnidae
      (Mollusca, Bivalvia): evidence for high levels of cryptic species diversity.
AB  - The family Pinnidae Leach, 1819, includes approximately 50 species of large
      subtidal and coastal marine bivalves. These commercially important species occur
      in tropical and temperate waters around the world and are most frequently found
      in seagrass meadows. The taxonomy of the family has been revised a number of
      times since the early 20th Century, the most recent revision recognizing 55
      species distributed in three genera: Pinna, Atrina and Streptopinna, the latter
      being monotypic. However, to date no phylogenetic analysis of the family has been
      conducted using morphological or molecular data. The present study analyzed 306
      pinnid specimens from around the world, comprising the three described genera and
      ca. 25 morphospecies. We sequenced the mitochondrial genes 16S rRNA and
      cytochrome c oxidase subunit I, and the nuclear ribosomal genes 18S rRNA and 28S
      rRNA. Phylogenetic analysis of the data revealed monophyly of the genus Atrina
      but also that the genus Streptopinna is nested within Pinna. Based on the strong
      support for this relationship we propose a new status for Streptopinna Martens,
      1880 and treat it as a subgenus (status nov.) of Pinna Linnaeus, 1758. The
      phylogeny and the species delimitation analyses suggest the presence of cryptic
      species in many morphospecies displaying a wide Indo-Pacific distribution,
      including Pinna muricata, Atrina assimilis, A. exusta and P. (Streptopinna)
      saccata but also in the Atlantic species A. rigida. Altogether our results
      highlight the challenges associated with morphological identifications in
      Pinnidae due to the presence of both phenotypic plasticity and morphological
      stasis and reveal that many pinnid species are not as widely distributed as
      previously thought. 

PMID- 24569018
TI  - Feeling the heat in sport.

PMID- 24569017
TI  - Do clinical trials of treatment of alcohol dependence adequately enroll
      participants with co-occurring independent mood and anxiety disorders? An
      analysis of data from the National Epidemiologic Survey on Alcohol and Related
      Conditions (NESARC).
AB  - BACKGROUND: In the care of alcohol-dependent patients, co-occurring independent
      (ie, not substance-induced) mood and anxiety disorders present a significant
      challenge. Clinical trials of alcohol dependence treatment could help clinicians
      meet this challenge, but only if they enroll such complex patients. This study
      examined whether such individuals are likely to be included in alcohol dependence
      treatment trials under typical eligibility criteria. METHOD: Data were derived
      from the 2001-2002 National Epidemiologic Survey on Alcohol and Related
      Conditions (NESARC), a national representative sample of 43,093 adults in the
      United States population. Psychiatric diagnoses were made according to the DSM-IV
      criteria with the Alcohol Use Disorder and Associated Disabilities Interview
      Schedule-DSM-IV Version (AUDADIS-IV). RESULTS: Of 1,484 alcohol-dependent
      participants, 39.22% (SE = 1.67) had a co-occurring independent mood or anxiety
      disorder; more than 60% of these individuals would be ineligible for an alcohol
      dependence treatment trial under typical eligibility criteria. Alcohol-dependent
      individuals with current major depressive episode, mania, dysthymia, panic
      disorder, and generalized anxiety disorder were particularly likely to be
      excluded from clinical trials. In a subsample of 185 individuals who had sought
      alcohol treatment, 52.59% (SE = 4.42) had an independent mood or anxiety
      disorder. Remarkably, almost all of these individuals (96.93%, SE = 1.97) would
      have been ineligible for clinical trials. CONCLUSIONS: Independent mood and
      anxiety disorders are prevalent in the alcohol-dependent population but not in
      clinical trial research samples. For alcohol dependence treatment trials to
      adequately inform clinical practice, the enrollment of patients with co-occurring
      mood or anxiety disorders must be increased, through trials tailored to this
      population, a general relaxation of overly stringent eligibility criteria, or
      both.

PMID- 24569019
TI  - Forward-backward postural protective stepping responses in young and elderly
      adults.
AB  - OBJECTIVES: Protective steps are essential for fall avoidance. Most studies only
      examined forwards stepping despite considerable bio-mechanical and visual
      differences between the forwards and backwards directions. We assess forward
      backward differences in protective steps in a young and elderly group. METHODS:
      Protective stepping responses were elicited by a platform moving unpredictably
      either forwards or backwards. For control purposes, voluntary steps, in response
      to vibration cues on the forehead or occiput were also recorded. Reaction time
      (RT), length and angular velocity of the steps were measured in 13 young (age 19
      35years) and 13 elderly (age 58-86years) healthy volunteers. RESULTS: (i)
      Protective vs voluntary steps: protective steps were earlier, faster and longer
      than voluntary steps. (ii) Forwards-backwards differences: RT was quicker for
      backwards than forwards protective steps, in contrast to voluntary steps where
      RTs were similar in the two directions. (iii) Age difference: the elderly had
      universally slower steps and they generated shorter backwards than forwards
      protective steps. CONCLUSIONS: Protective steps appear more robust than voluntary
      steps - they are earlier (shorter RT), longer and faster than voluntary steps,
      indicating an automatic rather than a volitional reaction. Backwards protective
      steps occur earlier than forwards; such promptness may have evolved out of bio
      mechanical features which make falling backwards easier. Since our elderly
      subjects had an average age <70years, their slower and shorter protective
      backwards steps may represent the first abnormality in this rescue postural
      response. The findings in the elderly may partly depend on dysfunction in fronto
      basal ganglia postural loops.

PMID- 24569021
TI  - Atherosclerosis and atrial fibrillation--two closely intertwined diseases.

PMID- 24569022
TI  - Pneumothorax recurrence related to high-speed lift.

PMID- 24569020
TI  - Carotid intima-media thickness is associated with incidence of hospitalized
      atrial fibrillation.
AB  - OBJECTIVE: Carotid intima-media thickness (IMT) is a measure of arterial
      thickening and a risk predictor for myocardial infarction and stroke. It is
      unclear whether IMT also predicts atrial fibrillation (AF). We explored the
      association between IMT and incidence of first AF hospitalization in a population
      based cohort. METHODS: IMT was measured in 4846 subjects from the general
      population (aged 46-68 years, 60% women) without a history of AF, heart failure
      or myocardial infarction. The Swedish in-patient register was used for retrieval
      of AF cases. IMT was studied in relation to incidence of AF. RESULTS: During a
      mean follow-up of 15.3 years, 353 subjects (181 men, 172 women, 4.8 per 1000
      person-years) were hospitalized with a diagnosis of AF. After adjustment for
      cardiovascular risk factors, the hazard ratio (HR) for incidence of AF was 1.61
      (95% confidence interval (CI): 1.14-2.27) for 4th vs. 1st quartile of IMT in the
      common carotid artery. This relationship was also independent of occurrence of
      carotid plaque. The results were similar for IMT in the bifurcation. CONCLUSION:
      Carotid IMT was independently associated with incidence of hospitalized AF in
      this study of middle-aged subjects from the general population. The results
      suggest that arterial thickening can predict future AF.

PMID- 24569023
TI  - Venous gangrene and intravascular coagulation and fibrinolysis in a patient
      treated with rivaroxaban.

PMID- 24569024
TI  - Implementing new guidelines in the management of blood cholesterol.

PMID- 24569025
TI  - Reply: Hereditary myopathy with early respiratory failure is caused by mutations
      in the titin FN3 119 domain.

PMID- 24569026
TI  - Predicting essential genes for identifying potential drug targets in Aspergillus
      fumigatus.
AB  - BACKGROUND: Aspergillus fumigatus (Af) is a ubiquitous and opportunistic pathogen
      capable of causing acute, invasive pulmonary disease in susceptible hosts.
      Despite current therapeutic options, mortality associated with invasive Af
      infections remains unacceptably high, increasing 357% since 1980. Therefore,
      there is an urgent need for the development of novel therapeutic strategies,
      including more efficacious drugs acting on new targets. Thus, as noted in a
      recent review, "the identification of essential genes in fungi represents a
      crucial step in the development of new antifungal drugs". Expanding the target
      space by rapidly identifying new essential genes has thus been described as "the
      most important task of genomics-based target validation". RESULTS: In previous
      research, we were the first to show that essential gene annotation can be
      reliably transferred between distantly related four Prokaryotic species. In this
      study, we extend our machine learning approach to the much more complex
      Eukaryotic fungal species. A compendium of essential genes is predicted in Af by
      transferring known essential gene annotations from another filamentous fungus
      Neurospora crassa. This approach predicts essential genes by integrating diverse
      types of intrinsic and context-dependent genomic features encoded in microbial
      genomes. The predicted essential datasets contained 1674 genes. We validated our
      results by comparing our predictions with known essential genes in Af, comparing
      our predictions with those predicted by homology mapping, and conducting
      conditional expressed alleles. We applied several layers of filters and selected
      a set of potential drug targets from the predicted essential genes. Finally, we
      have conducted wet lab knockout experiments to verify our predictions, which
      further validates the accuracy and wide applicability of the machine learning
      approach. CONCLUSIONS: The approach presented here significantly extended our
      ability to predict essential genes beyond orthologs and made it possible to
      predict an inventory of essential genes in Eukaryotic fungal species, amongst
      which a preferred subset of suitable drug targets may be selected. By selecting
      the best new targets, we believe that resultant drugs would exhibit an
      unparalleled clinical impact against a naive pathogen population. Additional
      benefits that a compendium of essential genes can provide are important
      information on cell function and evolutionary biology. Furthermore, mapping
      essential genes to pathways may also reveal critical check points in the
      pathogen's metabolism. Finally, this approach is highly reproducible and
      portable, and can be easily applied to predict essential genes in many more
      pathogenic microbes, especially those unculturable.

PMID- 24569028
TI  - C-reactive protein and risk of cardiovascular and all-cause mortality in 268 803
      East Asians.
AB  - AIMS: C-reactive protein concentrations are decreased in Asians compared with
      people of white European ethnicity. It is uncertain whether C-reactive protein is
      a robust biomarker of cardiovascular disease (CVD) in Asians. This study aimed to
      determine the association between C-reactive protein and CVD and all-cause
      mortality in a large population of Koreans. METHODS AND RESULTS: Mortality
      outcomes for 268 803 Koreans enrolled in a health screening programme with
      measurements of C-reactive protein at baseline and median follow-up of 4.49 years
      (1 155 930 person-years) were analysed. A subset (48%) of subjects had a repeat C
      reactive protein measurement during follow-up. The median (interquartile)
      baseline C-reactive protein values were higher in men than in women [0.6 (0.3
      1.3) vs. 0.4 (0.1-1.1), P < 0.001]. Only 8.6% of men and 6.2% of women met the
      standard cut point for C-reactive protein >3 mg/L, which represents the top
      tertile in white populations. During a median follow-up of 4.49 years (1 155 930
      person-years), 1047 died; 187 died of CVD causes. In men but not women, baseline
      C-reactive protein quartiles were linearly associated with both CVD and all-cause
      mortality (P < 0.001), even after adjustment for known CVD risk factors.
      Regardless of baseline C-reactive protein concentration, any increase or decrease
      in C-reactive protein over time did not affect the HR for all-cause, or CVD
      mortality. Models with C-reactive protein yielded a net reclassification
      improvement for CVD mortality of 24.9% (P = 0.04) for individuals with
      intermediate risk. CONCLUSIONS: C-reactive protein concentrations are
      substantially lower in Koreans than reported for whites populations. Nonetheless,
      C-reactive protein levels are associated with CVD and all-cause mortality in
      Korean men. Standard cut points for C-reactive protein may under-represent Asians
      at risk for CVD.

PMID- 24569027
TI  - Mitochondrial damage-associated molecular patterns and vascular function.
AB  - Immune system activation occurs not only due to foreign stimuli, but also due to
      endogenous molecules. As such, endogenous molecules that are released into the
      circulation due to cell death and/or injury alarm the immune system that
      something has disturbed homeostasis and a response is needed. Collectively, these
      molecules are known as damage-associated molecular patterns (DAMPs).
      Mitochondrial DAMPs (mtDAMPs) are potent immunological activators due to the
      bacterial ancestry of mitochondria. Mitochondrial DAMPs are recognized by
      specific pattern recognition receptors of the innate immune system, some of which
      are expressed in the cardiovascular system. Cell death leads to release of
      mtDAMPs that may induce vascular changes by mechanisms that are currently not
      well understood. This review will focus on recently published evidence linking
      mtDAMPs and immune system activation to vascular dysfunction and cardiovascular
      disease.

PMID- 24569029
TI  - Low-density lipoprotein particle diameter and mortality: the Ludwigshafen Risk
      and Cardiovascular Health Study.
AB  - AIMS: The aim of the study was to examine whether differences in average diameter
      of low-density lipoprotein (LDL) particles were associated with total and
      cardiovascular mortality. METHODS AND RESULTS: We studied 1643 subjects referred
      to coronary angiography, who did not receive lipid-lowering drugs. During a
      median follow-up of 9.9 years, 398 patients died, of these 246 from
      cardiovascular causes. We calculated average particle diameters of LDL from the
      composition of LDL obtained by beta-quantification. When LDL with intermediate
      average diameters (16.5-16.8 nm) were used as reference category, the hazard
      ratios (HRs) adjusted for cardiovascular risk factors for death from any cause
      were 1.71 (95% CI: 1.31-2.25) and 1.24 (95% CI: 0.95-1.63) in patients with large
      (>16.8 nm) or small LDL (<16.5 nm), respectively. Adjusted HRs for death from
      cardiovascular causes were 1.89 (95% CI: 1.32-2.70) and 1.54 (95% CI: 1.06-2.12)
      in patients with large or small LDL, respectively. Patients with large LDL had
      higher concentrations of the inflammatory markers interleukin (IL)-6 and C
      reactive protein than patients with small or intermediate LDL. Equilibrium
      density gradient ultracentrifugation revealed characteristic and distinct
      profiles of LDL particles in persons with large (approximately even distribution
      of intermediate-density lipoproteins and LDL-1 through LDL-6) intermediate (peak
      concentration at LDL-4) or small (peak concentration at LDL-6) average LDL
      particle diameters. CONCLUSIONS: Calculated LDL particle diameters identify
      patients with different profiles of LDL subfractions. Both large and small LDL
      diameters are independently associated with increased risk mortality of all
      causes and, more so, due to cardiovascular causes compared with LDL of
      intermediate size.

PMID- 24569030
TI  - Population and economic impact of the 2013 ACC/AHA guidelines compared with
      European guidelines to prevent cardiovascular disease.

PMID- 24569032
TI  - Efficacy and safety of apixaban compared with aspirin in patients who previously
      tried but failed treatment with vitamin K antagonists: results from the AVERROES
      trial.
AB  - AIM: The AVERROES double-blinded, randomized trial demonstrated that apixaban
      reduces the risk of stroke or systemic embolism (SSE) by 55% compared with
      aspirin without an increase in major bleeding in patients with atrial
      fibrillation either who previously tried but failed vitamin K antagonists (VKA)
      therapy or who were expected to be unsuitable for VKA therapy. In this pre
      specified analysis, we explored the consistency of the results in the subgroup of
      patients who tried but failed VKA therapy. METHODS AND RESULTS: Of 5599 patients,
      2216 (40%) had previously failed VKA treatment [main reasons: poor international
      normalized ratio (INR) control 42%, refusal 37%, bleeding on VKA 8%]. Compared
      with those expected to be unsuitable for VKA therapy, those who had previously
      failed were older, more often male, had higher body mass index, more likely to
      have moderate renal impairment and a history of stroke and less likely to have
      heart failure or to be medically undertreated. The effects of apixaban compared
      with aspirin were consistent in those who previously failed and those who were
      expected to be unsuitable, for both SSE (P interaction 0.13) and major bleeding
      (P interaction 0.74) and were also consistent among different subgroups of
      patients who had previously failed VKA therapy defined by reasons for
      unsuitability, age, sex, renal function, CHADS2 score, aspirin dose, duration,
      indication, and quality of INR control of prior VKA use. CONCLUSION: The efficacy
      and safety of apixaban compared with aspirin is consistent in subgroups of
      patients who have previously attempted but failed VKA therapy, irrespective of
      the reason for discontinuation.

PMID- 24569031
TI  - Long-term clinical outcome after intracoronary application of bone marrow-derived
      mononuclear cells for acute myocardial infarction: migratory capacity of
      administered cells determines event-free survival.
AB  - BACKGROUND: In the REPAIR-AMI trial, intracoronary infusion of bone marrow
      derived cells (BMCs) was associated with a significantly greater recovery of
      contractile function in patients with acute myocardial infarction (AMI) at 4
      month follow-up than placebo infusion. The current analysis investigates clinical
      outcome and predictors of event-free survival at 5 years. METHODS AND RESULTS: In
      the multicentre, placebo-controlled, double-blind REPAIR-AMI trial, 204 patients
      received intracoronary infusion of BMCs (n = 101) or placebo (n = 103) into the
      infarct vessel 3-7 days following successful percutaneous coronary intervention.
      Fifteen patients died in the placebo group compared with seven patients in the
      BMC group (P = 0.08). Nine placebo-treated patients and five BMC-treated patients
      required rehospitalization for chronic heart failure (P = 0.23). The combined
      endpoint cardiac/cardiovascular/unknown death or rehospitalisation for heart
      failure was more frequent in the placebo compared with the BMC group (18 vs. 10
      events; P = 0.10). Univariate predictors of adverse outcomes were age, the
      CADILLAC risk score, aldosterone antagonist and diuretic treatment, changes in
      left ventricular ejection fraction, left ventricular end-systolic volume, and N
      terminal pro-Brain Natriuretic Peptide (all P < 0.01) at 4 months in the entire
      cohort and in the placebo group. In contrast, in the BMC group, only the basal (P
      = 0.02) and the stromal cell-derived factor-1-induced (P = 0.05) migratory
      capacity of the administered BMC were associated with improved clinical outcome.
      CONCLUSION: In patients of the REPAIR-AMI trial, established clinical parameters
      are associated with adverse outcome at 5 years exclusively in the placebo group,
      whereas the migratory capacity of the administered BMC determines event-free
      survival in the BMC-treated patients. These data disclose a potency-effect
      relationship between cell therapy and long-term outcome in patients with AMI.

PMID- 24569033
TI  - Isolation and identification of acaricidal compounds in Eupatorium adenophorum
      petroleum ether extract and determination of their acaricidal activity against
      Psoroptes cuniculi.
AB  - We used multiple silica gel column chromatography and thin-layer chromatography
      coupled with (1)H nuclear magnetic resonance (NMR) and (13)C NMR to separate and
      identify the active acaricidal ingredients in Eupatorium adenophorum petroleum
      ether extract. The acaricidal activity of each compound was tested against
      Psoroptes cuniculi in vitro. Three compounds had strong acaricidal activity
      against P. cuniculi in vitro. The insecticidal effect of 0.5% compound 9beta
      hydroxy-ageraphorone was better than the insecticidal effect of fenvalerate, and
      compounds 9-oxo-ageraphorone and 9-oxo-10,11-dehydro-ageraphorone exhibited
      higher insecticidal effects than 9beta-hydroxy-ageraphorone. Thus, the E.
      adenophorum petroleum ether extract contains an effective composition of
      acaricides that could potentially be developed as a promising plant-origin
      acaricide. 

PMID- 24569034
TI  - The critical value of remnant liver volume-to-body weight ratio to estimate
      posthepatectomy liver failure in cirrhotic patients.
AB  - BACKGROUND: The extensive use of major hepatectomy for liver malignancies with
      cirrhosis increases the risk of posthepatectomy liver failure (PHLF), which is
      associated with a high frequency of postoperative complications, mortality, and
      an increased length of hospital stay. Remnant liver volume-to-body weight ratio
      (RLV-BWR) is more specific than the ratio of RLV-to-total liver volume (RLV-TLV)
      in predicting postoperative course after major hepatectomy in normal liver.
      Patients having normal liver with an anticipated RLV-BWR <=0.5% are at
      considerable risk for hepatic dysfunction and postoperative mortality. In the
      present study, the critical value of RLV-BWR after liver resection in cirrhotic
      liver was investigated. PATIENTS AND METHODS: Thirty one patients who underwent
      hepatectomy for hepatocellular carcinoma in one medical treatment unit of West
      China Hospital from September 2012 to December 2012 were retrospectively enrolled
      in study. Volumetric measurements of TLV using computed tomography were obtained
      before hepatectomy. PHLF was diagnosed by the "50-50 criteria." The influence of
      RLV-TLV and RLV-BWR on the occurrence of PHLF was investigated, and the critical
      value of RLV-BWR was concluded. RESULTS: According to the occurrence of PHLF, the
      patients were retrospectively divided into PHLF group and non-PHLF group. There
      were no statistical differences of preoperative indicators between the two
      groups. The intraoperative indicators including the resected liver volume, RLV
      TLV, and RLV-BWR were statistically significant (P < 0.05) between the two
      groups. The postoperative indicators including total bilirubin (TBIL),
      international normalized ratio, and peritoneal drainage fluid at the third and
      the fifth day after surgery were statistically significant (P < 0.05) between the
      two groups. Area under the receiver operating characteristic curve (ROC curve)
      predicted by RLV-BWR to the incidence of PHLF was 0.864 (P = 0.019) with 95%
      confidence interval (95% CI = 0.608-0.819), and the sensitivity and specialty
      rate were 70% and 95%, which were more than 50% and 70%, respectively. It
      suggested that the critical value of RLV-BWR (1.4%) had a certain predictive
      value on PHLF. Area under the receiver operating characteristic curve predicted
      by RLV-TLV to the incidence of PHLF was 0.568 (P = 0.628) with 95% confidence
      interval (95% CI = 0.376-0.747), and the sensitivity and specialty rate were
      42.9% and 82.6%, respectively. The sensitivity (42.9%) <50% suggested that the
      critical value of RLV-TLR (51%) had a poor predictive value on PHLF. According to
      the curve critical value 1.4% of RLV-BWR, the patients were divided into RLV-BWR
      >=1.4% group and RLV-BWR <1.4% group, and the incidence of PHLF between the two
      groups was statistically significant (P = 0.006). CONCLUSIONS: RLV-BWR was more
      specific than RLV-TLV in predicting PHLF after major hepatectomy of cirrhotic
      liver. Patients with an anticipated RLV-BWR <1.4% are at considerable risk for
      PHLF.

PMID- 24569035
TI  - Draft genome sequence of Bacillus firmus DS1.
AB  - Bacillus firmus DS1, an aerobic, Gram-positive, spore-forming bacterium isolated
      from marine sediment of the China South Sea coast. Here, the first draft genome
      sequence of B. firmus DS1 that may help us to clarify the evolutionary status of
      B. firmus, also will give the opportunity to provide the genetic basis for heavy
      metal ion absorption in environmental bioremediation, the enzymes in industrial
      production and more other active ingredients application. 

PMID- 24569036
TI  - Interaction of light and temperature signalling.
AB  - Light and temperature are arguably two of the most important signals regulating
      the growth and development of plants. In addition to their direct energetic
      effects on plant growth, light and temperature provide vital immediate and
      predictive cues for plants to ensure optimal development both spatially and
      temporally. While the majority of research to date has focused on the
      contribution of either light or temperature signals in isolation, it is becoming
      apparent that an understanding of how the two interact is essential to appreciate
      fully the complex and elegant ways in which plants utilize these environmental
      cues. This review will outline the diverse mechanisms by which light and
      temperature signals are integrated and will consider why such interconnected
      systems (as opposed to entirely separate light and temperature pathways) may be
      evolutionarily favourable. 

PMID- 24569037
TI  - Reduced handgrip strength as a marker of frailty predicts clinical outcomes in
      patients with heart failure undergoing ventricular assist device placement.
AB  - BACKGROUND: Heart failure (HF) is associated with the derangement of muscle
      structure and metabolism, contributing to exercise intolerance, frailty, and
      mortality. Reduced handgrip strength is associated with increased patient frailty
      and higher morbidity and mortality. We evaluated handgrip strength as a marker of
      muscle function and frailty for prediction of clinical outcomes after ventricular
      assist device (VAD) implantation in patients with advanced HF. METHODS AND
      RESULTS: Handgrip strength was measured in 72 patients with advanced HF before
      VAD implantation (2.3 +/- 4.9 days pre-VAD). We analyzed dynamics in handgrip
      strength, laboratory values, postoperative complications, and mortality. Handgrip
      strength correlated with serum albumin levels (r = 0.334, P = .004). Compared
      with baseline, handgrip strength increased post-VAD implantation by 18.2 +/- 5.6%
      at 3 months (n = 29) and 45.5 +/- 23.9% at 6 months (n = 27). Patients with a
      handgrip strength <25% of body weight had an increased risk of mortality,
      increased postoperative complications, and lower survival after VAD implantation.
      CONCLUSION: Patients with advanced HF show impaired handgrip strength indicating
      a global myopathy. Handgrip strength <25% of body weight is associated with
      higher postoperative complication rates and increased mortality after VAD
      implantation. Thus, the addition of measures of skeletal muscle function
      underlying the frailty phenotype to traditional risk markers might have
      incremental prognostic value in patients undergoing evaluation for VAD placement.

PMID- 24569038
TI  - Use of an activated beta-catenin to identify Wnt pathway target genes in
      caenorhabditis elegans, including a subset of collagen genes expressed in late
      larval development.
AB  - The Wnt signaling pathway plays a fundamental role during metazoan development,
      where it regulates diverse processes, including cell fate specification, cell
      migration, and stem cell renewal. Activation of the beta-catenin
      dependent/canonical Wnt pathway up-regulates expression of Wnt target genes to
      mediate a cellular response. In the nematode Caenorhabditis elegans, a canonical
      Wnt signaling pathway regulates several processes during larval development;
      however, few target genes of this pathway have been identified. To address this
      deficit, we used a novel approach of conditionally activated Wnt signaling during
      a defined stage of larval life by overexpressing an activated beta-catenin
      protein, then used microarray analysis to identify genes showing altered
      expression compared with control animals. We identified 166 differentially
      expressed genes, of which 104 were up-regulated. A subset of the up-regulated
      genes was shown to have altered expression in mutants with decreased or increased
      Wnt signaling; we consider these genes to be bona fide C. elegans Wnt pathway
      targets. Among these was a group of six genes, including the cuticular collagen
      genes, bli-1 col-38, col-49, and col-71. These genes show a peak of expression in
      the mid L4 stage during normal development, suggesting a role in adult cuticle
      formation. Consistent with this finding, reduction of function for several of the
      genes causes phenotypes suggestive of defects in cuticle function or integrity.
      Therefore, this work has identified a large number of putative Wnt pathway target
      genes during larval life, including a small subset of Wnt-regulated collagen
      genes that may function in synthesis of the adult cuticle. 

PMID- 24569041
TI  - The role of social interaction and pedagogical cues for eliciting and reducing
      overimitation in preschoolers.
AB  - The tendency to imitate causally irrelevant actions is termed overimitation. Here
      we investigated (a) whether communication of a model performing irrelevant
      actions is necessary to elicit overimitation in preschoolers and (b) whether
      communication of another model performing an efficient action modulates the
      subsequent reduction of overimitation. In the study, 5-year-olds imitated
      irrelevant actions both when they were modeled by a communicative and pedagogical
      experimenter and when they were modeled by a non-communicative and non
      pedagogical experimenter. However, children stopped using the previously learned
      irrelevant actions only when they were subsequently shown the more efficient way
      to achieve the goal by a pedagogical experimenter. Thus, communication leads
      preschoolers to adapt their imitative behavior but does not seem to affect
      overimitation in the first place. Results are discussed with regard to the
      importance of communication for the transmission of cultural knowledge during
      development. 

PMID- 24569040
TI  - Levator hiatus dimensions in late pregnancy and the process of labor: a 3- and 4
      dimensional transperineal ultrasound study.
AB  - OBJECTIVE: The objectives of the investigation were to study the association
      between levator hiatus dimensions in late pregnancy and both the length of second
      stage of labor and also the delivery mode in women delivering their first child.
      STUDY DESIGN: In this cohort study, 231 nulliparous women were examined with 3-
      and 4-dimensional transperineal ultrasonography at 37 weeks of gestation. The
      anteroposterior, transverse diameter, and the area of levator hiatus were
      measured at rest, during levator ani muscle contraction, and during Valsalva
      maneuver. The second stage of labor was divided into passive and active second
      stage and delivery modes into normal vaginal or instrumental deliveries. Spearman
      correlation coefficient, independent-sample t test, and standard logistic
      regression were used for analysis. RESULTS: Larger levator hiatus dimensions at
      rest and during contraction at 37 weeks of gestation correlated with a shorter
      duration of the active second stage in women with normal vaginal delivery
      (Spearman correlation coefficient, -0.13 to -0.35, P <= .08). Women having normal
      vaginal deliveries had significantly larger transverse diameter at rest, during
      contraction, and during Valsalva maneuver compared with women having instrumental
      deliveries (mean difference, 0.29; 95% confidence interval (CI), 0.16-0.41; mean
      difference, 0.33; 95% CI, 0.21-0.44 and mean difference, 0.24; 95% CI, 0.06-0.42;
      P < .05). The same was true for the levator hiatus area at rest and during
      contraction (mean difference, 1.22; 95% CI, 0.37-2.07 and mean difference, 0.84;
      95% CI, 0.22-1.46; P < .01). These estimates were unchanged by adjustments in the
      logistic regression analysis. CONCLUSION: Larger levator hiatus dimensions in
      late pregnancy had a significant association with a shorter active second stage
      of labor and normal vaginal delivery.

PMID- 24569042
TI  - Does bladder augmentation negatively affect renal transplant outcome in posterior
      urethral valve patients?
AB  - OBJECTIVE: Although renal transplant (RT) is a safe and effective treatment for
      end-stage renal disease, the outcome of RT has been mixed for posterior urethral
      valve (PUV) patients. In addition, some PUV patients need an augmentation
      cystoplasty (AC), which may negatively affect their RT outcome. The aim of this
      study is to compare RT outcome between PUV children with and without AC.
      MATERIALS AND METHODS: Between 1985 and 2012 a total of 309 children received 369
      RTs at our institution. Among these patients, 36 were had classified as having
      PUV. Of these, 12 underwent an AC before RT (AC group) and 24 did not (controls).
      Data, including age at transplant, allograft source, urological complications,
      urinary tract infection (UTI) incidence, the presence of vesicoureteral reflux
      (VUR), and patient and graft survival, were compared between groups. RESULTS:
      Mean age at RT and mean follow-up were 7.6 versus 7.9 years and 8.9 versus 7.9
      years in the AC group and in the control group, respectively (not significant
      [NS]). Allografts were from living donors in 50% of the AC group and in 41.6% of
      the controls (NS). The rate of UTI was 0.02 UTI/patient/year and 0.004
      UTI/patient/year in the AC and control group, respectively (p = 0.001). Of the
      nine patients with UTI in the augmented group, five (55.5%) had VUR, while 5/8
      (62.5%) patients in the control group with UTI had VUR. All patients with VUR in
      either group had UTIs previously. Of the five AC patients with more than three
      UTIs, two (40%) were non-compliant with clean intermittent catheterization (CIC),
      and UTI incidence was not associated with either a Mitrofanoff conduit or the
      urethra being used for CIC. Graft function at the end of study was 87.8 +/- 40.5
      ml/min/m(2) in the AC group and 88.17 +/- 28.20 ml/min/m(2) in the control group
      (NS). The 10-year graft survival rate was 100% in AC group and 84.8% in controls.
      Two patients in the AC group lost their grafts (mean follow-up 13.3 +/- 0.8
      years) and five in the control group (mean follow-up 7.1 +/- 4.7 years).
      CONCLUSIONS: Bladder augmentation does not negatively affect renal outcome in PUV
      patients undergoing transplantation. However, recurrent UTIs are more frequent in
      transplanted PUV patients with an AC than in those without AC, and they are
      generally related to non-compliance with CIC or the presence of VUR but, mostly,
      they will not result in impaired graft function.

PMID- 24569039
TI  - Extensive cotransformation of natural variation into chromosomes of naturally
      competent Haemophilus influenzae.
AB  - Naturally competent bacterial species actively take up environmental DNA and can
      incorporate it into their chromosomes by homologous recombination. This can bring
      genetic variation from environmental DNA to recipient chromosomes, often in
      multiple long "donor" segments. Here, we report the results of genome sequencing
      96 colonies of a laboratory Haemophilus influenzae strain, which had been
      experimentally transformed by DNA from a diverged clinical isolate. Donor
      segments averaged 6.9 kb (spanning several genes) and were clustered into
      recombination tracts of ~19.5 kb. Individual colonies had replaced from 0.1 to
      3.2% of their chromosomes, and ~1/3 of all donor-specific single-nucleotide
      variants were present in at least one recombinant. We found that nucleotide
      divergence did not obviously limit the locations of recombination tracts,
      although there were small but significant reductions in divergence at
      recombination breakpoints. Although indels occasionally transformed as parts of
      longer recombination tracts, they were common at breakpoints, suggesting that
      indels typically block progression of strand exchange. Some colonies had
      recombination tracts in which variant positions contained mixtures of both donor
      and recipient alleles. These tracts were clustered around the origin of
      replication and were interpreted as the result of heteroduplex segregation in the
      original transformed cell. Finally, a pilot experiment demonstrated the utility
      of natural transformation for genetically dissecting natural phenotypic
      variation. We discuss our results in the context of the potential to merge
      experimental and population genetic approaches, giving a more holistic
      understanding of bacterial gene transfer. 

PMID- 24569043
TI  - Recovery of volatile fatty acids via membrane contactor using flat membranes:
      experimental and theoretical analysis.
AB  - Volatile fatty acid (VFA) separation from synthetic VFA solutions and leachate
      was investigated via the use of a membrane contactor. NaOH was used as a
      stripping solution to provide constant concentration gradient of VFAs in both
      sides of a membrane. Mass flux (12.23 g/m(2)h) and selectivity (1.599) observed
      for acetic acid were significantly higher than those reported in the literature
      and were observed at feed pH of 3.0, flow rate of 31.5 +/- 0.9 mL/min, and
      stripping solution concentration of 1.0 N. This study revealed that the flow
      rate, stripping solution strength, and feed pH affect the mass transfer of VFAs
      through the PTFE membrane. Acetic and propionic acid separation performances
      observed in the present study provided a cost effective and environmental
      alternative due to elimination of the use of extractants.

PMID- 24569044
TI  - Investigation of the usage of centrifuging waste of mineral wool melt (CMWW),
      contaminated with phenol and formaldehyde, in manufacturing of ceramic products.
AB  - Large amounts of centrifuging waste of mineral wool melt (CMWW) are created
      during the production of mineral wool. CMWW is technogenic aluminum silicate raw
      material, formed from the particles of undefibred melt (60-70%) and mineral wool
      fibers (30-40%). 0.3-0.6% of organic binder with phenol and formaldehyde in its
      composition exists in this material. Objective of the research is to investigate
      the possibility to use CMWW as an additive for the production of ceramic
      products, by neutralising phenol and formaldehyde existing in CMWW. Formation
      masses were prepared by incorporating 10%, 20% and 30% of CMWW additive and
      burned at various temperatures. It was identified that the amount of 10-30% of
      CMWW additive influences the following physical and mechanical properties of the
      ceramic body: lowers drying and firing shrinkage, density, increases compressive
      strength and water absorption. Investigations carried out show that CMWW waste
      can be used for the production of ceramic products of various purposes.

PMID- 24569047
TI  - [Career preferences among medical students].
AB  - OBJECTIVE: Research on the preference of medical specialty among medical students
      in the Netherlands and the attractiveness of aspects of the medical profession
      during the period 2009-2013. DESIGN: Retrospective, descriptive research. METHOD:
      Data from medical students in the Netherlands who participated in the computer
      programme Inventory Medical Professionals Choice (IMBK) were analyzed with
      respect to their preference of medical specialty and the attractiveness of
      various aspects of the medical profession. The IMBK programme was available free
      of charge through the Royal Dutch Medical Association (KNMG) website 'Arts in
      Spe' (Future Physician) during the period 2009-2013. The content of the IMBK
      programme was based on the questionnaire from the medical profile book developed
      by the pharmaceutical company GlaxoSmithKline (GSK). RESULTS: General practice
      was the most popular specialty, particularly among female medical students, with
      interest increasing during the undergraduate medical curriculum. Hardly any
      students were interested in insurance medicine, occupational medicine and elderly
      medicine. Direct patient care was the most attractive professional aspect for
      medical students. Female students were more attracted to direct and prolonged
      patient contact than their male counterparts. The number of hours students wished
      to work in future declined during the course of the undergraduate curriculum, and
      women were more inclined to prefer regular working hours with adequate leisure
      time than men. CONCLUSION: During the course of the undergraduate medical
      curriculum, medical students changed their preference for medical specialty.
      Major differences exist between male and female students in terms of preference
      of medical specialty and attractiveness of aspects of the medical profession.

PMID- 24569045
TI  - Agomelatine in generalized anxiety disorder: an active comparator and placebo
      controlled study.
AB  - BACKGROUND: Agomelatine was efficacious in reducing symptoms in a short-term
      placebo-controlled trial in generalized anxiety disorder (GAD) and in preventing
      relapse in a longer term placebo-controlled study. An additional short-term
      placebo-controlled study is required by regulatory agencies to confirm the
      efficacy of agomelatine in GAD. METHOD: This 12-week, placebo-controlled, double
      blind, randomized, parallel group, international, multicenter study was designed
      to confirm the efficacy of agomelatine 25-50 mg/d in the treatment of patients
      with a primary DSM-IV-TR diagnosis of GAD. The primary outcome measure was the
      Hamilton Anxiety Rating Scale (HARS) total score. Assay sensitivity was evaluated
      by including an escitalopram (10-20 mg/d) group. SETTINGS: The study was
      undertaken in 45 clinical centers in Argentina, Czech Republic, Finland, South
      Korea, Poland, Russia, and Slovakia from April 2010 to July 2011. RESULTS: One
      hundred thirty-nine outpatients were included in the agomelatine group, 131 in
      the placebo group, and 142 in the escitalopram group. Agomelatine significantly
      reduced mean (SD) HARS total score (agomelatine-placebo difference: 4.71 [1.03],
      P <.0001) and had significant effects on secondary outcome measures, including
      psychic and somatic HARS subscales, response rate (estimate [standard error])
      (agomelatine-placebo difference: 27.4% [5.9%], P< .0001), remission on the HARS
      (agomelatine-placebo difference: 16.8% [5.4%], P = .002), Clinical Global
      Impressions-Severity of Illness scale (CGI-S) (P < .001), functional impairment
      (P < .0001), and sleep quality (P < .001). Findings were confirmed in the subset
      of more severely ill patients (HARS total score >= 25 with or without CGI-S >= 5
      at baseline). Agomelatine was well tolerated by patients, with no more adverse
      events than placebo. Escitalopram was similarly efficacious but was accompanied
      by a higher incidence of adverse events compared to placebo. CONCLUSIONS: In
      clinical practice, agomelatine has at least similar efficacy to that of
      escitalopram for the short-term treatment of GAD and is well tolerated. TRIAL
      REGISTRATION: Controlled-Trials.com identifier: ISRCTN03554974.

PMID- 24569048
TI  - [Acute pancreatitis after propofol administration].
AB  - BACKGROUND: Propofol is a widely used and safe hypnotic agent. Complications
      include pain on injection, dose-dependent hypotension, allergic reactions and
      hypertriglyceridemia; after long-term administration, propofol infusion syndrome
      can occur. A less common but serious complication is acute pancreatitis. CASE
      DESCRIPTION: In this report, a 72-year-old male is described who underwent total
      hip replacement and subsequent revision one year later. On both occasions
      propofol was administered. Both procedures were complicated by acute
      pancreatitis. Various known causes for pancreatitis were systematically excluded
      except for propofol which seemed to have caused both incidents of pancreatitis.
      However, a multifactorial cause could not be completely ruled out. CONCLUSION:
      Pancreatitis after propofol administration is a rare complication. This rare
      complication, however, is likely to become more frequent with increasing demand
      for propofol use and its administration by different care professionals. In
      patients who experience abdominal symptoms after propofol administration,
      pancreatitis should be considered as a possible cause and appropriate diagnostic
      testing performed.

PMID- 24569049
TI  - [Screening: management after incomplete colonoscopy could be improved].
AB  - In 2014 in the Netherlands a national screening programme for bowel cancer was
      started in which a colonoscopy is performed after a positive immunochemical
      faecal occult blood test. If colonoscopy is incomplete a CT colonography (CTC) is
      offered in order to visualize the remaining colon. Balloon endoscopy (BE), double
      or single-balloon, is an effective and safe endoscopic alternative which has
      advantages over CTC, including the option of endoscopic polypectomy and
      histological examination. However, its cost and the need for an additional
      procedure on a different day are disadvantageous. BE deserves a place in the
      national screening programme for bowel cancer after an incomplete colonoscopy, as
      a possible alternative for CTC and certainly after finding polyps on CTC. Because
      expertise in BE and its availability are limited, in each screening region some
      centres should be appointed as designated referral centres to perform BE. 

PMID- 24569050
TI  - [Choice of continuing education requires guidance].
AB  - General practice seems to be the most popular discipline among Dutch medical
      students, despite increasing work pressure and administrative burden. In
      contrast, the interest for specialisation in geriatric, insurance and
      occupational medicine is slight. This is partly due to less exposure to these
      fields during the undergraduate training and lack of encouragement to choose for
      these disciplines. Additionally, although medical students prefer regular working
      hours, the workload remains high, in spite of an increasing number of graduates
      who are unable to find a job. More central control in health manpower planning
      and guidance of students in making a choice for a professional career is
      required. 

PMID- 24569051
TI  - Safety evaluation of fish protein hydrolysate supplementation in malnourished
      children.
AB  - Amizate(r) is a proprietary protein hydrolysate preparation derived from Atlantic
      salmon (Salmo salar) using endogenous hydrolytic enzymes; it contains mostly free
      amino acids and short peptides, as well as small amounts of micronutrients (i.e.,
      vitamins and minerals). In this study, the safety of supplementation with fish
      protein hydrolysate (Amizate(r)) was examined in 438 malnourished children in a
      randomized, placebo-controlled, double-blind, and parallel study. The children
      were between the ages of six to eight and met the Gomez classification for mild
      or moderate malnutrition. They were randomized to receive one of three
      interventions for four months, including a chocolate drink (control), or
      Amizate(r) (3 or 6g/day) in a chocolate drink. Administration of Amizate(r) was
      well-tolerated, with no adverse events reported. Growth (i.e., body weight gain,
      changes in height, and body mass index) was not negatively impacted by
      administration of Amizate(r), and routine biochemical analysis of blood and urine
      samples did not reveal any abnormalities that were attributable to the
      intervention. Findings from this study demonstrate that daily consumption of 3 or
      6g of fish protein hydrolysate (Amizate(r)) was safe and suitable for
      supplementing the diets of malnourished children. 

PMID- 24569052
TI  - Entorhinal cortex contribution to contextual fear conditioning extinction and
      reconsolidation in rats.
AB  - During contextual fear conditioning a rat learns a temporal contiguity
      association between the exposition to a previously neutral context (CS) and an
      aversive unconditioned stimulus (US) as a footshock. This condition determines in
      the rat the freezing reaction during the subsequent re-exposition to the context.
      Potentially the re-exposition without US presentation initiates two opposing and
      competing processes: reconsolidation and extinction. Reconsolidation process re
      stabilizes and strengthens the original memory and it is initiated by a brief re
      exposure to context. Instead the extinction process leads to the decrease of the
      expression of the original memory and it is triggered by prolonged re-exposure to
      the context. Here we analyzed the entorhinal cortex (ENT) participation in
      contextual fear conditioning reconsolidation and extinction. The rats were
      trained in contextual fear conditioning and 24h later they were subjected either
      to a brief (2 min) reactivation session or to a prolonged (120 min) re-exposition
      to context to induce extinction of the contextual fear memory. Immediately after
      the reactivation or the extinction session, the animals were submitted to
      bilateral ENT TTX inactivation. Memory retention was assessed as conditioned
      freezing duration measured 72 h after TTX administration. The results showed that
      ENT inactivation both after reactivation and extinction session was followed by
      contextual freezing retention impairment. Thus, the present findings point out
      that ENT is involved in contextual fear memory reconsolidation and extinction.
      This neural structure might be part of parallel circuits underlying two phases of
      contextual fear memory processing.

PMID- 24569054
TI  - Characterization of quinol-dependent nitric oxide reductase from Geobacillus
      stearothermophilus: enzymatic activity and active site structure.
AB  - Nitric oxide reductase (NOR) catalyzes the reduction of nitric oxide to generate
      nitrous oxide. We recently reported on the crystal structure of a quinol
      dependent NOR (qNOR) from Geobacillus stearothermophilus [Y. Matsumoto, T. Tosha,
      A.V. Pisliakov, T. Hino, H. Sugimoto, S. Nagano, Y. Sugita and Y. Shiro, Nat.
      Struct. Mol. Biol. 19 (2012) 238-246], and suggested that a water channel from
      the cytoplasm, which is not observed in cytochrome c-dependent NOR (cNOR),
      functions as a pathway transferring catalytic protons. Here, we further
      investigated the functional and structural properties of qNOR, and compared the
      findings with those for cNOR. The pH optimum for the enzymatic reaction of qNOR
      was in the alkaline range, whereas Pseudomonas aeruginosa cNOR showed a higher
      activity at an acidic pH. The considerably slower reduction rate, and a
      correlation of the pH dependence for enzymatic activity and the reduction rate
      suggest that the reduction process is the rate-determining step for the NO
      reduction by qNOR, while the reduction rate for cNOR was very fast and therefore
      is unlikely to be the rate-determining step. A close examination of the heme/non
      heme iron binuclear center by resonance Raman spectroscopy indicated that qNOR
      has a more polar environment at the binuclear center compared with cNOR. It is
      plausible that a water channel enhances the accessibility of the active site to
      solvent water, creating a more polar environment in qNOR. This structural feature
      could control certain properties of the active site, such as redox potential,
      which could explain the different catalytic properties of the two NORs. This
      article is part of a Special Issue entitled: 18th European Bioenergetic
      Conference. 

PMID- 24569057
TI  - WITHDRAWN: Is there life after the Mesothelioma and Radical Surgery trial? Does
      extrapleural pneumonectomy still have a role in the management of pleural
      mesothelioma? A 13-year, single-center experience.
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- 24569055
TI  - Development of ventricular assist devices in China: present status, opportunities
      and challenges.
AB  - The growing number of heart failure patients and the scarcity of organ donors
      account for the huge need for the development of mechanical circulatory systems,
      including ventricular assist devices (VADs) and artificial hearts, in China.
      Several research programmes on blood pumps have been under way for the last three
      decades. However, unlike in other countries, the development of VADs has been
      extremely slow, and no system is currently approved and available for clinical
      application. There are many reasons for this situation. This article provides an
      overview of the present development of experimental and clinical research on VADs
      in China. In addition, the challenges for the clinical development of mechanical
      circulatory support in China are discussed. 

PMID- 24569056
TI  - Profound hypothermia compared with moderate hypothermia in repair of acute type A
      aortic dissection.
AB  - OBJECTIVE: To determine the impact of the degree of hypothermia on surgical
      outcomes in patients undergoing repair of acute type A aortic dissection.
      METHODS: Between 1990 and 2010, 211 consecutive patients underwent surgical
      repair of type A aortic syndrome. Patients with acute type A dissection (n = 128)
      were included. Circulatory arrest with profound hypothermia (PH; <20  degrees C)
      was used in 75 patients (58.6%) and circulatory arrest with moderate hypothermia
      (MH; 22-28  degrees C) in 53 patients (41.4%). Subacute or chronic dissections,
      intramural hematoma and penetrating aortic ulcers were excluded. RESULTS:
      Preoperative acute kidney injury was higher in the PH group (18.9% vs 5.3%, P =
      .01). Axillary or direct aortic cannulation was more prevalent in the MH group
      (33.9% vs 11.1%, P = .01). The duration of circulatory arrest was 25.9 +/- 14.3
      and 28.9 +/- 19.9 minutes in the MH and PH groups, respectively (P = .3). The
      composite outcome of mortality, low cardiac output syndrome or stroke was higher
      in the PH group (52.8% vs 24%, P < .001). Cardiopulmonary bypass time and blood
      transfusion were significantly higher in the PH group (P = .04). By multivariable
      analysis (C = 0.80), PH (odds ratio [OR], 7.6; 95% confidence interval [CI], 3.0
      21.1) and preoperative shock (OR, 3.5; 95% CI, 1.3-10.1) were independent
      predictors of the composite outcome. CONCLUSIONS: MH was independently associated
      with a lower risk of a composite outcome of mortality and major adverse cardiac
      and cerebrovascular events during repair of acute type A dissection. Use of
      moderate hypothermic circulatory arrest avoids the detrimental effects of PH
      without an increase in the risk of neurologic injury in this study.

PMID- 24569053
TI  - Characterisation of the active/de-active transition of mitochondrial complex I.
AB  - Oxidation of NADH in the mitochondrial matrix of aerobic cells is catalysed by
      mitochondrial complex I. The regulation of this mitochondrial enzyme is not
      completely understood. An interesting characteristic of complex I from some
      organisms is the ability to adopt two distinct states: the so-called
      catalytically active (A) and the de-active, dormant state (D). The A-form in situ
      can undergo de-activation when the activity of the respiratory chain is limited
      (i.e. in the absence of oxygen). The mechanisms and driving force behind the A/D
      transition of the enzyme are currently unknown, but several subunits are most
      likely involved in the conformational rearrangements: the accessory subunit 39kDa
      (NDUFA9) and the mitochondrially encoded subunits, ND3 and ND1. These three
      subunits are located in the region of the quinone binding site. The A/D
      transition could represent an intrinsic mechanism which provides a fast response
      of the mitochondrial respiratory chain to oxygen deprivation. The physiological
      role of the accumulation of the D-form in anoxia is most probably to protect
      mitochondria from ROS generation due to the rapid burst of respiration following
      reoxygenation. The de-activation rate varies in different tissues and can be
      modulated by the temperature, the presence of free fatty acids and divalent
      cations, the NAD(+)/NADH ratio in the matrix, the presence of nitric oxide and
      oxygen availability. Cysteine-39 of the ND3 subunit, exposed in the D-form, is
      susceptible to covalent modification by nitrosothiols, ROS and RNS. The D-form in
      situ could react with natural effectors in mitochondria or with pharmacological
      agents. Therefore the modulation of the re-activation rate of complex I could be
      a way to ameliorate the ischaemia/reperfusion damage. This article is part of a
      Special Issue entitled: 18th European Bioenergetic Conference. Guest Editors:
      Manuela Pereira and Miguel Teixeira. 

PMID- 24569058
TI  - Seasonal dynamics of the cestode fauna in spiny dogfish, Squalus acanthias
      (Squaliformes: Squalidae).
AB  - This study furthers understanding of cestode infections in a marine environment
      through time and space by following seasonal fluctuations in infection parameters
      of three cestode species (Gilquinia squali, Trilocularia gracilis and
      Phyllobothrium squali) parasitizing spiny dogfish (Squalus acanthias) in the
      northwest Atlantic and comparing them to work previously published from the
      northeast Atlantic on T. gracilis. For each cestode species, host size, season
      and presence of the other cestode species were analysed using generalized linear
      models to determine if they were good predictors of prevalence and intensity.
      Infection parameters differed across season for the three cestode species.
      However, within T. gracilis seasonal trends were found to be remarkably similar
      on both sides of the Atlantic, differing only in a somewhat delayed decline in
      prevalence in the northwest Atlantic. The differences seen in infection measures
      across cestode species likely reflect the unique life history strategies of
      different parasite species. While general trends appear to be maintained across
      disparate localities, variation seen is likely due to differences in
      accessibility to intermediate hosts and host diet across sites. The knowledge
      gained from understanding cestode infections in the vast ocean environment allows
      us to speculate about the factors driving fluctuations in parasite infections in
      elasmobranchs.

PMID- 24569059
TI  - IBS with intestinal microbial dysbiosis: a new and clinically relevant subgroup?

PMID- 24569060
TI  - Authors' response: The role of risedronate in osteopenia in Crohn's disease.

PMID- 24569061
TI  - Sleep quality implicates in life quality: an analysis about children who suffered
      burns.

PMID- 24569062
TI  - A randomized, observer-blind comparison between the Neurotip mounted Neuropen and
      a disposable plastic neurological wheel for assessing the level of spinal
      blockade at cesarean section.
AB  - BACKGROUND: Various methods are used to assess the height of sensory block to
      touch under spinal anesthesia for cesarean section. We tested a novel,
      inexpensive, miniature, user-dependent plastic neurological wheel against the
      user-independent Neurotip mounted Neuropen. METHODS: Patients received either
      spinal or combined spinal-epidural anesthesia. For each patient assessment, the
      devices were randomly assigned to one of two independent investigators. The order
      of device application was randomly permuted. Neither researcher was involved with
      anesthetic care. At 5-min intervals for 20 min after spinal injection, and again
      at the end of the operation, the levels of block to loss-of-touch sensation were
      assessed. While one investigator evaluated the block, the other left the
      operating room and vice versa. Mixed-effects regression and Bland-Altman analysis
      were used to weigh agreement between devices. RESULTS: The mean difference in
      level-to-touch was 0.04 (95% CI -0.18, 0.27) dermatome levels. Measurement error
      standard deviation associated with the Neurotip mounted Neuropen and plastic
      neurological wheel was 1.36 (95% CI 1.26, 1.41) and 1.33 (95% CI 1.26, 1.46)
      dermatome levels, respectively. The difference in measurement error standard
      deviation was -0.03 (95% CI -0.16, 0.24). This evidence excludes the possibility,
      with 95% confidence, of clinically significant bias or measurement error
      differences between methods. Occasional wide variances in dermatome level were
      observed with both instruments at the initial assessment only. CONCLUSION: The
      compact plastic neurological wheel is as clinically reliable as the Neurotip
      mounted Neuropen.

PMID- 24569063
TI  - An investigational antiviral drug, DAS181, effectively inhibits replication of
      zoonotic influenza A virus subtype H7N9 and protects mice from lethality.
AB  - Human infections caused by avian influenza A virus type subtype H7N9 have been
      associated with substantial morbidity and mortality. Emergence of virus variants
      carrying markers of decreased susceptibility to neuraminidase inhibitors was
      reported. Here we show that DAS181 (Fludase), an antiviral drug with sialidase
      activity, potently inhibited replication of wild-type influenza A(H7N9) and its
      oseltamivir-resistant R292K variants in mice. A once-daily administration
      initiated early after lethal infection hampered body weight loss and completely
      protected mice from lethality. We observed a time-dependent effect for 24-72-hour
      delayed DAS181 treatments on morbidity and mortality. The results warrant further
      investigation of DAS181 for influenza treatment. 

PMID- 24569065
TI  - Heparin-induced thrombocytopenia and the health economic analysis of argatroban.

PMID- 24569066
TI  - IV. Surrogate measures, do they really describe anaesthetic state?

PMID- 24569064
TI  - Seroprevalence of 8 oncogenic human papillomavirus genotypes and acquired
      immunity against reinfection.
AB  - BACKGROUND: Natural human papillomavirus (HPV) antibody titers have shown
      protection against subsequent HPV infection, but previous studies were restricted
      to few HPV genotypes. We examined the association of naturally occurring
      antibodies against 8 carcinogenic HPV types with subsequent infections. METHODS:
      A total of 2302 women enrolled in the Atypical Squamous Cells of Undetermined
      Significance/Low-Grade Squamous Intraepithelial Lesion Triage Study provided
      blood samples at baseline. Serum samples were tested for antibodies against 8
      carcinogenic HPV genotypes (16, 18, 31, 33, 35, 45, 52, and 58) using a multiplex
      serology assay. We analyzed the relationship between HPV antibodies and HPV
      infection during 2 years of follow-up among women negative for the specific HPV
      type at baseline. RESULTS: Baseline seroprevalence for HPV16 L1 was associated
      with decreased risk of DNA positivity for HPV16 (odds ratio, 0.39 [95% confidence
      interval, .18-.86]) at >=2 follow-up visits. We observed similar but
      nonsignificant decreased risks for HPV18 and 31. These findings were restricted
      to women reporting a new sex partner during follow-up. There was no association
      between baseline seroprevalence and detection of precancer during follow-up.
      CONCLUSIONS: Seroprevalence conferred protection against subsequent HPV infection
      for HPV16 and indicated possible protection for 2 other genotypes, suggesting
      that this effect is common to several HPV genotypes.

PMID- 24569067
TI  - Quercetin attenuates chronic ethanol hepatotoxicity: implication of "free" iron
      uptake and release.
AB  - Emerging evidence has displayed that oxygen free radicals especially ones
      promoted by "free" iron play an important role in the development of alcoholic
      liver disease (ALD). Naturally-occurring quercetin has been reported to prevent
      ALD and iron overload-induced damage aside from the "free" iron. The purpose was
      to explore the potential mechanisms by which quercetin arrests alcohol-induced
      "free" iron disorder. Chronic alcohol (30% of total calories) or iron (0.2%)-fed
      adult male C57BL/J mice for 15 weeks resulted in significantly elevated levels of
      hepatic iron, labile iron pool-Fe and serum non-transferrin bound iron,
      accompanied with sustained oxidative damage. The hepatotoxicity was further
      exacerbated by ethanol and iron. Quercetin (100 mg/kg. body weight) alleviated
      the detrimental effects induced by ethanol and/or iron. The expressions of
      divalent metal transporter 1, zinc transporter member 14, mucolipin 1,
      transferrin receptor 1 (TfR1) and ferritin were up-regulated by ethanol and/or
      iron, which were partially normalized by quercetin. Quercetin prevented ethanol
      induced hepatotoxicity, which may be partially attributed to the alleviated
      disorder of bound iron and "free" iron. The significant suppression of ethanol
      stimulated molecules for "free" iron uptake and release may contribute to the
      hepatoprotective effect of quercetin, although TfR1-mediated physiological
      pathway of iron uptake also played a role.

PMID- 24569068
TI  - Hepatoprotective effect of polyphenols rich methanolic extract of Amorphophallus
      commutatus var. wayanadensis against CCl4 induced hepatic injury in swiss albino
      mice.
AB  - The present study is to evaluate the hepatoprotective and antioxidant activity of
      methanolic extract of Amorphophallus commutatus var. wayanadensis against carbon
      tetrachloride induced hepatotoxicity in mice models. Hepatic injury was induced
      by injecting 0.2% CCl4 in olive oil intra peritoneally on 15th day of drug
      administration. Hepatoprotective activity was evaluated by estimating the levels
      of serum markers like alanine aminotransferase (ALT) and aspartate
      aminotransferase (AST), alkaline phosphatase (ALP), bilirubin and
      histopathological studies. Antioxidant potential of the extract was estimated by
      measuring the levels of antioxidant enzymes, superoxide dismutase (SOD), catalase
      (CAT), glutathione-s-transferase (GST), glutathione peroxidase (GPx) and total
      reduced glutathione in the liver samples. Histopathological and biochemical
      results elicited the methanolic extract of A. commutatus has significant
      hepatoprotective activity comparable to the standard silymarin. The extract also
      showed dose dependent increase of antioxidant enzymes in CCl4 induced
      hepatotoxicity models. The methanolic extract of A. commutatus showed significant
      hepatoprotective and antioxidant activity which might be attributed due to the
      polyphenolic compounds present in the extract. 

PMID- 24569069
TI  - The interaction of plant-growth regulators with serum albumin: molecular modeling
      and spectroscopic methods.
AB  - The affinity between two plant-growth regulators (PGRs) and human serum albumin
      (HSA) was investigated by molecular modeling techniques and spectroscopic
      methods. The results of molecular modeling simulations revealed that
      paclobutrazol (PAC) could bind on both site I and site II in HSA where the
      interaction was easier, while uniconazole (UNI) could not bind with HSA.
      Furthermore, the results of fluorescence spectroscopy, three-dimensional (3D)
      fluorescence spectroscopy and circular dichroism (CD) spectroscopy suggested that
      PAC had a strong ability to quench the intrinsic fluorescence of HSA. The binding
      affinity (Kb) and the amounts of binding sites (n) between PAC and HSA at 291 K
      were estimated as 2.37*10(5) mol L(-1) and 1, respectively, which confirm that
      PAC mainly binds on site II of HSA. An apparent distance between the Trp214 and
      PAC was 4.41 nm. Additionally, the binding of PAC induced the conformational
      changes of disulfide bridges of HSA with the decrease of alpha-helix content.
      These studies provide more information on the potential toxicological effects and
      environmental risk assessment of PGRs.

PMID- 24569070
TI  - Organic versus conventional tomatoes: influence on physicochemical parameters,
      bioactive compounds and sensorial attributes.
AB  - The effect of organic and conventional agricultural systems on the
      physicochemical parameters, bioactive compounds content, and sensorial attributes
      of tomatoes ("Redondo" cultivar) was studied. The influence on phytochemicals
      distribution among peel, pulp and seeds was also accessed. Organic tomatoes were
      richer in lycopene (+20%), vitamin C (+30%), total phenolics (+24%) and
      flavonoids (+21%) and had higher (+6%) in vitro antioxidant activity. In the
      conventional fruits, lycopene was mainly concentrated in the pulp, whereas in the
      organic ones, the peel and seeds contained high levels of bioactive compounds.
      Only the phenolic compounds had a similar distribution among the different
      fractions of both types of tomatoes. Furthermore, a sensorial analysis indicated
      that organic farming improved the gustative properties of this tomato cultivar. 

PMID- 24569071
TI  - The mental health characteristics of pregnant women with depressive symptoms
      identified by the Edinburgh Postnatal Depression Scale.
AB  - OBJECTIVE: Few studies are available on the effectiveness of screening tools such
      as the Edinburgh Postnatal Depression Scale (EPDS) in pregnancy or the extent to
      which such tools may identify women with mental disorders other than depression.
      We therefore aimed to investigate the mental health characteristics of pregnant
      women who screen positive on the EPDS. METHOD: Consecutive women receiving
      antenatal care in primary care clinics (from November 2006 to July 2011) were
      invited to complete the EPDS in week 16 of pregnancy. All women who scored above
      11 (screen positive) on the EPDS and randomly selected women who scored below 12
      (screen negative) were invited to participate in a psychiatric diagnostic
      interview. RESULTS: 2,411 women completed the EPDS. Two hundred thirty-three
      women (9.7%) were screened positive in week 16, of whom 153 (66%) agreed to a
      psychiatric diagnostic interview. Forty-eight women (31.4%) were diagnosed with
      major depressive disorder according to DSM-IV criteria, 20 (13.1%) with bipolar
      disorder, 93 (60.8%) with anxiety disorders (including 27 [17.6%] with obsessive
      compulsive disorder [OCD]), 8 (5.2%) with dysthymia, 18 (11.8%) with somatoform
      disorder, 3 (2%) with an eating disorder, and 7 (4.6%) with current substance
      abuse. Women who screened positive were significantly more likely to have
      psychosocial risk factors, including being unemployed (chi(2)(1) = 23.37, P
      <=.001), lower educational status (chi(2)(1)= 31.68, P <= .001), and a history of
      partner violence (chi(2)(1) = 10.30, P <= 001), compared with the women who
      screened negative. CONCLUSIONS: Use of the EPDS early in the second trimester of
      pregnancy identifies a substantial number of women with potentially serious
      mental disorders other than depression, including bipolar disorder, OCD, and
      eating disorders. A comprehensive clinical assessment is therefore necessary
      following use of the EPDS during pregnancy to ensure that women who screen
      positive receive appropriate mental health management.

PMID- 24569072
TI  - The role of leptin in gastric cancer: clinicopathologic features and molecular
      mechanisms.
AB  - Obesity is associated with certain types of cancer, including gastric cancer.
      However, it is still unclear whether obesity-related cytokine, leptin, is
      implicated in gastric cancer. Therefore, we aimed to investigate the role of
      leptin in gastric cancer. The expression of leptin and its receptor, Ob-R, was
      assessed by immunohistochemical staining and was compared in patients with
      gastric adenoma (n=38), early gastric cancer (EGC) (n=38), and advanced gastric
      cancer (AGC) (n=38), as a function of their clinicopathological characteristics.
      Gastric cancer cell lines were studied to investigate the effects of leptin on
      the signal transducer and activator of transcription-3 (STAT3) and extracellular
      receptor kinase 1/2 (ERK1/2) signaling pathways using MTT assays, immunoblotting,
      and inhibition studies. Leptin was expressed in gastric adenomas (42.1%), EGCs
      (47.4%), and AGCs (43.4%). Ob-R expression tended to increase from gastric
      adenoma (2%), through EGC (8%), to AGC (18%). Leptin induced the proliferation of
      gastric cancer cells by activating STAT3 and ERK1/2 and up-regulating the
      expression of vascular endothelial growth factor (VEGF). Blocking Ob-R with
      pharmacological inhibitors and by RNAi decreased both the leptin-induced
      activation of STAT3 and ERK1/2 and the leptin-induced expression of VEGF. Leptin
      plays a role in gastric cancer by stimulating the proliferation of gastric cancer
      cells via activating the STAT3 and ERK1/2 pathways. 

PMID- 24569074
TI  - A nanobody directed to a functional epitope on VEGF, as a novel strategy for
      cancer treatment.
AB  - Compelling evidence suggests that vascular endothelial growth factor (VEGF), due
      to its essential role in angiogenesis, is a critical target for cancer treatment.
      Neutralizing monoclonal antibodies against VEGF are important class of drugs used
      in cancer therapy. However, the cost of production, large size, and
      immunogenicity are main drawbacks of conventional monoclonal therapy. Nanobodies
      are the smallest antigen-binding antibody fragments, which occur naturally in
      camelidae. Because of their remarkable features, we decided to use an immune
      library of nanobody to direct phage display to recognition of novel functional
      epitopes on VEGF. Four rounds of selection were performed and six phage-displayed
      nanobodies were obtained from an immune phage library. The most reactive clone in
      whole-cell ELISA experiments, was purified and assessed in proliferation
      inhibition assay. Purified ZFR-5 not only blocked interaction of VEGF with its
      receptor in cell ELISA experiments, but also was able to significantly inhibit
      proliferation response of human umbilical vein endothelial cells to VEGF in a
      dose-dependent manner. Taken together, our study demonstrates that by using whole
      cell ELISA experiments, nanobodies against antigenic regions included in
      interaction of VEGF with its receptors can be directed. Because of unique and
      intrinsic properties of a nanobody and the ability of selected nanobody for
      blocking the epitope that is important for biological function of VEGF, it
      represents novel potential drug candidate. 

PMID- 24569073
TI  - The processed isoform of the translation termination factor eRF3 localizes to the
      nucleus to interact with the ARF tumor suppressor.
AB  - The eukaryotic releasing factor eRF3 is a multifunctional protein that plays
      pivotal roles in translation termination as well as the initiation of mRNA decay.
      eRF3 also functions in the regulation of apoptosis; eRF3 is cleaved at Ala73 by
      an as yet unidentified protease into processed isoform of eRF3 (p-eRF3), which
      interacts with the inhibitors of apoptosis proteins (IAPs). The binding of p-eRF3
      with IAPs leads to the release of active caspases from IAPs, which promotes
      apoptosis. Although full-length eRF3 is localized exclusively in the cytoplasm, p
      eRF3 localizes in the nucleus as well as the cytoplasm. We here focused on the
      role of p-eRF3 in the nucleus. We identified leptomycin-sensitive nuclear export
      signal (NES) at amino acid residues 61-71 immediately upstream of the cleavage
      site Ala73. Thus, the proteolytic cleavage of eRF3 into p-eRF3 leads to release
      an amino-terminal fragment containing NES to allow the relocalization of eRF3
      into the nucleus. Consistent with this, p-eRF3 more strongly interacted with the
      nuclear ARF tumor suppressor than full-length eRF3. These results suggest that
      while p-eRF3 interacts with IAPs to promote apoptosis in the cytoplasm, p-eRF3
      also has some roles in regulating cell death in the nucleus. 

PMID- 24569075
TI  - Evidence that a synthetic amyloid-beta oligomer-binding peptide (ABP) targets
      amyloid-beta deposits in transgenic mouse brain and human Alzheimer's disease
      brain.
AB  - The synthetic ~5 kDa ABP (amyloid-beta binding peptide) consists of a region of
      the 228 kDa human pericentrioloar material-1 (PCM-1) protein that selectively and
      avidly binds in vitro Abeta1-42 oligomers, believed to be key co-drivers of
      Alzheimer's disease (AD), but not monomers (Chakravarthy et al., (2013) [3]). ABP
      also prevents Abeta1-42 from triggering the apoptotic death of cultured human
      SHSY5Y neuroblasts, likely by sequestering Abeta oligomers, suggesting that it
      might be a potential AD therapeutic. Here we support this possibility by showing
      that ABP also recognizes and binds Abeta1-42 aggregates in sections of cortices
      and hippocampi from brains of AD transgenic mice and human AD patients. More
      importantly, ABP targets Abeta1-42 aggregates when microinjected into the
      hippocampi of the brains of live AD transgenic mice.

PMID- 24569076
TI  - Dimethyl fumarate inhibits the expression and function of hypoxia-inducible
      factor-1alpha (HIF-1alpha).
AB  - Osteocyte hypoxia has been induced by skeletal unloading and fracture. Hypoxia
      dependent regulation of gene expression is mediated by hypoxia-sensitive
      transcription factors such as hypoxia-inducible factor-1alpha (HIF-1alpha).
      Dimethyl fumarate (DMF) is a recently approved first-line therapy for multiple
      sclerosis. However, the role of DMF in regulating HIF-1alpha expression and
      function has not been evaluated. In this study, we found that DMF inhibited
      hypoxia-induced expression of HIF-1alpha and its target genes such as interleukin
      8 (IL-8) and vascular endothelial growth factor (VEGF) in MC3T3 E1 cells.
      Mechanistically, DMF promoted HIF-1alpha degradation in a proteasome-dependent
      but von Hippel-Lindau (VHL) protein-independent manner. Importantly, we found
      that DMF disrupted the interaction between HIF-1alpha and its chaperone heat
      shock protein 90 (Hsp90) but promoted the interaction between HIF-1alpha and the
      receptor of activated protein kinase C (RACK1). These data suggest that DMF might
      promote degradation of HIF-1alpha by affecting its folding and maturation. Based
      on these observations, we conclude that DMF is a novel inhibitor of HIF-1alpha. 

PMID- 24569077
TI  - Clusterin stimulates the chemotactic migration of macrophages through a pertussis
      toxin sensitive G-protein-coupled receptor and Gbetagamma-dependent pathways.
AB  - Clusterin induces the expression of various chemotactic cytokines including tumor
      necrosis factor-alpha (TNF-alpha) in macrophages and is involved in the cell
      migration. According to the results of this study, clusterin induced the
      directional migration (chemotaxis) of macrophages based on a checkerboard
      analysis. The chemotactic activity of clusterin was prevented by pretreatment
      with pertussis toxin (PTX), indicating that the Galphai/o-protein coupled
      receptor (GPCR) was involved in the chemotactic response of clusterin. Clusterin
      stimulated chemotaxis was abrogated in a dose-dependent manner by pretreatment
      with gallein (a Gbetagamma inhibitor), indicating the involvement of Gbetagamma
      released from the GPCR. In addition, inhibitors of phospholipase C (PLC, U73122)
      and phosphoinositide 3-kinase (PI3K, LY294002), the key targets of Gbetagamma
      binding and activation, suppressed chemotactic migration by clusterin. The
      phosphorylation of Akt induced by clusterin was blocked by pretreatment with
      gallein or LY294002 but not with U73122, indicating that Gbetagamma released from
      the PTX-sensitive Gi protein complex activated PLC and PI3K/Akt signaling
      pathways separately. The activation of cellular MAP kinases was essential in that
      their inhibitors blocked clusterin-induced chemotaxis, and Gbetagamma was
      required for the activation of MAP kinases because gallein reduced their
      phosphorylations induced by clusterin. In addition, the inflammation-induced
      migration of macrophages was greatly reduced in clusterin-deficient mice based on
      a thioglycollate-induced peritonitis model system. These results suggest that
      clusterin stimulates the chemotactic migration of macrophages through a PTX
      sensitive GPCR and Gbetagamma-dependent pathways and describe a novel role of
      clusterin as a chemoattractant of monocytes/macrophages, suggesting that
      clusterin may serve as a molecular bridge between inflammation and its remodeling
      of related tissue by recruiting immune cells. 

PMID- 24569078
TI  - Identification of a chemical inhibitor for nuclear speckle formation:
      implications for the function of nuclear speckles in regulation of alternative
      pre-mRNA splicing.
AB  - Nuclear speckles are subnuclear structures enriched with RNA processing factors
      and poly (A)(+) RNAs comprising mRNAs and poly (A)(+) non-coding RNAs (ncRNAs).
      Nuclear speckles are thought to be involved in post-transcriptional regulation of
      gene expression, such as pre-mRNA splicing. By screening 3585 culture extracts of
      actinomycetes with in situ hybridization using an oligo dT probe, we identified
      tubercidin, an analogue of adenosine, as an inhibitor of speckle formation, which
      induces the delocalization of poly (A)(+) RNA and dispersion of splicing factor
      SRSF1/SF2 from nuclear speckles in HeLa cells. Treatment with tubercidin also
      decreased steady-state MALAT1 long ncRNA, thought to be involved in the retention
      of SRSF1/SF2 in nuclear speckles. In addition, we found that tubercidin treatment
      promoted exon skipping in the alternative splicing of Clk1 pre-mRNA. These
      results suggest that nuclear speckles play a role in modulating the concentration
      of splicing factors in the nucleoplasm to regulate alternative pre-mRNA splicing.

PMID- 24569079
TI  - New fluorescent probes for ligand-binding assays of odorant-binding proteins.
AB  - Fluorescence-linked binding assays allow determination of dissociation constants
      at equilibrium and have recently become increasingly popular, thanks to their
      ease of operation. Currently used probes, such as 1-aminoanthracene and N-phenyl
      1-naphthylamine, are excited and emit in the ultraviolet region, but alternative
      ligands operating in the visible spectrum would be highly desirable for
      applications in biosensing devices. Based on the two above structures, we have
      designed and synthesised six new fluorescent probes to be used in ligand-binding
      assays. The compounds are derivatives of naphatalene, anthracene and fluoranthene
      and present two aromatic moieties linked by an amine nitrogen. We have measured
      the emission spectra of the new probes and their binding to three odorant-binding
      proteins. The probes bind the tested proteins with different affinities,
      generally with dissociation constants about one order of magnitude lower than the
      parent compounds. The extended aromatic systems present in the new compounds
      produced a shift of both excitation and emission peaks at higher wavelength,
      close or within the visible spectrum, thus facilitating measurements in
      biosensors for odorants and small organic molecules using optical devices. 

PMID- 24569080
TI  - microRNA-222 modulates liver fibrosis in a murine model of biliary atresia.
AB  - microRNA-222 (miR-222) has been shown to initiate the activation of hepatic
      stellate cells, which plays an important role in the pathogenesis of liver
      fibrosis. The aim of our study was to evaluate the role of miR-22 in a mouse
      model of biliary atresia (BA) induced by Rhesus Rotavirus (RRV) infection. New
      born Balb/c mice were randomized into control and RRV infected groups. The
      extrahepatic bile ducts were evaluated. The experimental group was divided into
      BA group and negative group based on histology. The expression of miR-222,
      protein phosphatase 2 regulatory subunit B alpha (PPP2R2A), proliferating cell
      nuclear antigen (PCNA) and phospho-Akt were detected. We found that the
      experimental group showed signs of cholestasis, retardation and extrahepatic
      biliary atresia. No abnormalities were found in the control group. In the BA
      group, miR-222, PCNA and Akt were highly expressed, and PPP2R2A expression was
      significantly inhibited. Our findings suggest that miR-222 profoundly modulated
      the process of fibrosis in the murine BA model, which might represent a potential
      target for improving BA prognosis. 

PMID- 24569081
TI  - A comparative analysis of comprehensive geriatric assessments for nursing home
      residents receiving palliative care: a systematic review.
AB  - BACKGROUND/OBJECTIVES: Nursing homes become important locations for palliative
      care. By means of comprehensive geriatric assessments (CGAs), an evaluation can
      be made of the different palliative care needs of nursing home residents. This
      review aims to identify all CGAs that can be used to assess palliative care needs
      in long-term care settings and that have been validated for nursing home
      residents receiving palliative care. The CGAs are evaluated in terms of
      psychometric properties and content comprehensiveness. DESIGN: A systematic
      literature search in electronic databases MEDLINE, Web of Science, EMBASE,
      Cochrane, CINAHL, and PsycInfo was conducted for the years 1990 to 2012. SETTING:
      Nursing homes. PARTICIPANTS: Nursing home residents with palliative care needs.
      MEASUREMENTS: Psychometric data on validity and reliability were extracted from
      the articles. The content comprehensiveness of the identified CGAs was analyzed,
      using the 13 domains for a palliative approach in residential aged care of the
      Australian Government Department of Health and Aging. RESULTS: A total of 1368
      articles were identified. Seven studies met our inclusion criteria, describing 5
      different CGAs that have been validated for nursing home residents with
      palliative care needs. All CGAs demonstrate moderate to high psychometric
      properties. The interRAI Palliative Care instrument (interRAI PC) covers all
      domains for a palliative approach in residential aged care of the Australian
      Government Department of Health and Aging. The McMaster Quality of Life Scale
      covers nine domains. All other CGAs cover seven domains or fewer. CONCLUSIONS:
      The interRAI PC and the McMaster Quality of Life Scale are considered to be the
      most comprehensive CGAs to evaluate the needs and preferences of nursing home
      residents receiving palliative care. Future research should aim to examine the
      effectiveness of the identified CGAs and to further validate the CGAs for nursing
      home residents with palliative care needs.

PMID- 24569082
TI  - Bilateral neck exploration in patients with primary hyperparathyroidism and
      discordant imaging results: a single-centre study.
AB  - INTRODUCTION: Focused parathyroidectomy is the treatment of choice for patients
      with concordant positive imaging. Bilateral cervical exploration is performed for
      cases with discordant imaging, yet more than 70% of those cases are the result of
      a single-gland disease. As focused parathyroidectomy is generally costless and
      harmless, for cases with discordant imaging, we tried to determine whether
      preoperative characteristics can lead to a diagnosis of single-gland disease.
      METHODS: This study included 182 patients treated for primary hyperparathyroidism
      by bilateral exploration from 2009 to 2012 at La Timone Hospital, Marseille,
      France. We classified patients based on preoperative images and pathological
      results (single-gland or multiglandular disease). We then compared the
      demographical, laboratory and imaging results. We also asked a senior nuclear
      medicine practitioner who was blind to the ultrasound and pathological results to
      perform a second reading. RESULTS: Of the total number of patients, 15.4% had
      negative, 54.4% discordant and 30.2% concordant imaging. After reviewing the
      scintigraphy results, 8% of the cases with discordant imaging would have been
      classified as concordant with ultrasound. Subtraction scintigraphy obtained
      better results than dual-phase scintigraphy (concordance with ultrasound in 50 vs
      31% with classical scintigraphy). For the cases of discordant imaging, no
      predictive factors of single-gland disease could be identified. Ultrasound and
      scintigraphy were similarly effective in determining the correct location of the
      abnormal gland. CONCLUSION: Discordant results of preoperative imaging modalities
      do not discriminate between uniglandular and multiglandular diseases in
      hyperparathyroidism. Diagnostic differentiation between the different causes of
      hyperparathyroidism requires improvements in imaging techniques and might benefit
      from subtraction scintigraphy.

PMID- 24569083
TI  - Editorial overview: cancer genomics: kill it. Kill it dead.

PMID- 24569084
TI  - Genetic characterization of the Neurospora crassa molybdenum cofactor
      biosynthesis.
AB  - Molybdenum (Mo) is a trace element that is essential for important cellular
      processes. To gain biological activity, Mo must be complexed in the molybdenum
      cofactor (Moco), a pterin derivative of low molecular weight. Moco synthesis is a
      multi-step pathway that involves a variable number of genes in eukaryotes, which
      are assigned to four steps of eukaryotic Moco biosynthesis. Moco biosynthesis
      mutants lack any Moco-dependent enzymatic activities, including assimilation of
      nitrate (plants and fungi), detoxification of sulfite (humans and plants) and
      utilization of hypoxanthine as sole N-source (fungi). We report the first
      comprehensive genetic characterization of the Neurospora crassa (N. crassa) Moco
      biosynthesis pathway, annotating five genes which encode all pathway enzymes, and
      compare it with the characterized Aspergillus nidulans pathway. Biochemical
      characterization of the corresponding knock-out mutants confirms our annotation
      model, documenting the N. crassa/A. nidulans (fungal) Moco biosynthesis as
      unique, combining the organizational structure of both plant and human Moco
      biosynthesis genes. 

PMID- 24569085
TI  - Implications of global budget payment system on nursing home costs.
AB  - Pressure on health care systems due to the increasing expenditures of the elderly
      population is pushing policy makers to adopt new regulation and payment schemes
      for nursing home services. We consider the behavior of nonprofit nursing homes
      under different payment schemes and empirically investigate the implications of
      prospective payments on nursing home costs under tightly regulated quality
      aspects. To evaluate the impact of the policy change introduced in 2006 in
      Southern Switzerland - from retrospective to prospective payment - we use a panel
      of 41 homes observed over a 10-years period (2001-2010). We employ a fixed
      effects model with a time trend that is allowed to change after the policy
      reform. There is evidence that the new payment system slightly reduces costs
      without impacting quality. 

PMID- 24569086
TI  - What is the impact of mental health-related stigma on help-seeking? A systematic
      review of quantitative and qualitative studies.
AB  - BACKGROUND: Individuals often avoid or delay seeking professional help for mental
      health problems. Stigma may be a key deterrent to help-seeking but this has not
      been reviewed systematically. Our systematic review addressed the overarching
      question: What is the impact of mental health-related stigma on help-seeking for
      mental health problems? Subquestions were: (a) What is the size and direction of
      any association between stigma and help-seeking? (b) To what extent is stigma
      identified as a barrier to help-seeking? (c) What processes underlie the
      relationship between stigma and help-seeking? (d) Are there population groups for
      which stigma disproportionately deters help-seeking? METHOD: Five electronic
      databases were searched from 1980 to 2011 and references of reviews checked. A
      meta-synthesis of quantitative and qualitative studies, comprising three parallel
      narrative syntheses and subgroup analyses, was conducted. RESULTS: The review
      identified 144 studies with 90,189 participants meeting inclusion criteria. The
      median association between stigma and help-seeking was d = - 0.27, with
      internalized and treatment stigma being most often associated with reduced help
      seeking. Stigma was the fourth highest ranked barrier to help-seeking, with
      disclosure concerns the most commonly reported stigma barrier. A detailed
      conceptual model was derived that describes the processes contributing to, and
      counteracting, the deterrent effect of stigma on help-seeking. Ethnic minorities,
      youth, men and those in military and health professions were disproportionately
      deterred by stigma. CONCLUSIONS: Stigma has a small- to moderate-sized negative
      effect on help-seeking. Review findings can be used to help inform the design of
      interventions to increase help-seeking.

PMID- 24569088
TI  - Morphine induces redox-based changes in global DNA methylation and
      retrotransposon transcription by inhibition of excitatory amino acid transporter
      type 3-mediated cysteine uptake.
AB  - Canonically, opioids influence cells by binding to a G protein-coupled opioid
      receptor, initiating intracellular signaling cascades, such as protein kinase,
      phosphatidylinositol 3-kinase, and extracellular receptor kinase pathways. This
      results in several downstream effects, including decreased levels of the reduced
      form of glutathione (GSH) and elevated oxidative stress, as well as epigenetic
      changes, especially in retrotransposons and heterochromatin, although the
      mechanism and consequences of these actions are unclear. We characterized the
      acute and long-term influence of morphine on redox and methylation status
      (including DNA methylation levels) in cultured neuronal SH-SY5Y cells. Acting via
      MU-opioid receptors, morphine inhibits excitatory amino acid transporter type 3
      mediated cysteine uptake via multiple signaling pathways, involving different G
      proteins and protein kinases in a temporal manner. Decreased cysteine uptake was
      associated with decreases in both the redox and methylation status of neuronal
      cells, as defined by the ratios of GSH to oxidized forms of glutathione and S
      adenosylmethionine to S-adenosylhomocysteine levels, respectively. Further,
      morphine induced global DNA methylation changes, including CpG sites in long
      interspersed nuclear elements (LINE-1) retrotransposons, resulting in increased
      LINE-1 mRNA. Together, these findings illuminate the mechanism by which morphine,
      and potentially other opioids, can influence neuronal-cell redox and methylation
      status including DNA methylation. Since epigenetic changes are implicated in drug
      addiction and tolerance phenomenon, this study could potentially extrapolate to
      elucidate a novel mechanism of action for other drugs of abuse. 

PMID- 24569089
TI  - Context-dependent antagonism between Akt inhibitors and topoisomerase poisons.
AB  - Signaling through the phosphatidylinositol-3 kinase (PI3K)/Akt pathway, which is
      aberrantly activated in >50% of carcinomas, inhibits apoptosis and contributes to
      drug resistance. Accordingly, several Akt inhibitors are currently undergoing
      preclinical or early clinical testing. To examine the effect of Akt inhibition on
      the activity of multiple widely used classes of antineoplastic agents, human
      cancer cell lines were treated with the Akt inhibitor A-443654 [(2S)-1-(1H-indol
      3-yl)-3-[5-(3-methyl-2H-indazol-5-yl)pyridin-3-yl]oxypropan-2-amine; ATP
      competitive] or MK-2206 (8-[4-(1-aminocyclobutyl)phenyl]-9-phenyl-2H
      [1,2,4]triazolo[3,4-f][1,6]naphthyridin-3-one;dihydrochloride; allosteric
      inhibitor) or with small interfering RNA (siRNA) targeting phosphoinositide
      dependent kinase 1 (PDK1) along with cisplatin, melphalan, camptothecin, or
      etoposide and assayed for colony formation. Surprisingly different results were
      observed when Akt inhibitors were combined with different drugs. Synergistic
      effects were observed in multiple cell lines independent of PI3K pathway status
      when A-443654 or MK-2206 was combined with the DNA cross-linking agents cisplatin
      or melphalan. In contrast, effects of the Akt inhibitors in combination with
      camptothecin or etoposide were more complicated. In HCT116 and DLD1 cells, which
      harbor activating PI3KCA mutations, A-443654 over a broad concentration range
      enhanced the effects of camptothecin or etoposide. In contrast, in cell lines
      lacking activating PI3KCA mutations, partial inhibition of Akt signaling
      synergized with camptothecin or etoposide, but higher A-443654 or MK-2206
      concentrations (>80% inhibition of Akt signaling) or PDK1 siRNA antagonized the
      topoisomerase poisons by diminishing DNA synthesis, a process that contributes to
      effective DNA damage and killing by these agents. These results indicate that the
      effects of combining inhibitors of the PI3K/Akt pathway with certain classes of
      chemotherapeutic agents might be more complicated than previously recognized. 

PMID- 24569091
TI  - Acetate/acetyl-CoA metabolism associated with cancer fatty acid synthesis:
      overview and application.
AB  - Understanding cancer-specific metabolism is important for identifying novel
      targets for cancer diagnosis and therapy. Induced acetate/acetyl CoA metabolism
      is a notable feature that is related to fatty acid synthesis supporting tumor
      growth. In this review, we focused on the recent findings related to cancer
      acetate/acetyl CoA metabolism. We also introduce [1-11C]acetate positron emission
      tomography (PET), which is a useful tool to visualize up-regulation of
      acetate/acetyl CoA metabolism in cancer, and discuss the utility of [1
      11C]acetate PET in cancer diagnosis and its application to personalized medicine.

PMID- 24569087
TI  - Molecular responses to hypoxia-inducible factor 1alpha and beyond.
AB  - Cellular response to changes in oxygen tension during normal development or
      pathologic processes is, in part, regulated by hypoxia-inducible factor (HIF), an
      oxygen-sensitive transcription factor. HIF activity is primarily controlled
      through post-translational modifications and stabilization of HIF-1alpha and HIF
      2alpha proteins and is regulated by a number of cellular pathways involving both
      oxygen-dependent and -independent mechanisms. Stabilization of HIF-1alpha
      activates transcription of genes that participate in key pathways in
      carcinogenesis, such as angiogenesis, dedifferentiation, and invasion. Since its
      discovery more than two decades ago, HIF-1alpha has become a hot topic in
      molecular research and has been implicated not only in disease pathology but also
      in prognosis. In this review, we will focus on recent insights into HIF-1alpha
      regulation, function, and gene expression. We will also discuss emerging data on
      the involvement of HIF in cancer prognosis and therapeutic interventions. 

PMID- 24569093
TI  - Towards precision medicine in childhood leukemia--insights from mutationally
      activated cytokine receptor pathways in acute lymphoblastic leukemia.
AB  - The successful therapy of childhood leukemia has been characterized by careful
      personalized adaptation of therapy by risk stratification. Yet almost all drugs
      are relatively non-specific. To achieve greater precision in therapy, druggable
      targets and specific targeting drugs are necessary. Here we review the recent
      discoveries of cytokine receptors and their signaling components in high risk
      leukemias and the potential approaches to target them. 

PMID- 24569090
TI  - Adaptations of energy metabolism during cerebellar neurogenesis are co-opted in
      medulloblastoma.
AB  - Recent studies show that metabolic patterns typical of cancer cells, including
      aerobic glycolysis and increased lipogenesis, are not unique to malignancy, but
      rather originate in physiologic development. In the postnatal brain, where
      sufficient oxygen for energy metabolism is scrupulously maintained, neural
      progenitors nevertheless metabolize glucose to lactate and prioritize lipid
      synthesis over fatty acid oxidation. Medulloblastoma, a cancer of neural
      progenitors that is the most common malignant brain tumor in children,
      recapitulates the metabolic phenotype of brain progenitor cells. During the
      physiologic proliferation of neural progenitors, metabolic enzymes generally
      associated with malignancy, including Hexokinase 2 (Hk2) and Pyruvate kinase M2
      (PkM2) configure energy metabolism to support growth. In these non-malignant
      cells, expression of Hk2 and PkM2 is driven by transcriptional regulators that
      are typically identified as oncogenes, including N-myc. Importantly, N-myc
      continues to drive Hk2 and PkM2 in medulloblastoma. Similarly E2F transcription
      factors and PPARgamma function in both progenitors and medulloblastoma to
      optimize energy metabolism to support proliferation. These findings show that the
      "metabolic transformation" that is a hallmark of cancer is not specifically
      limited to cancer. Rather, metabolic transformation represents a co-opting of
      developmental programs integral to physiologic growth. Despite their physiologic
      origins, the molecular mechanisms that mediate metabolic transformation may
      nevertheless present ideal targets for novel anti-tumor therapy. 

PMID- 24569094
TI  - The expression of endothelial barrier antigen (EBA) and S100B in the rat parietal
      cortex following brain irradiation.
AB  - OBJECTIVE: To visualize the dynamic expression of endothelial barrier antigen
      (EBA) and S100B in the rat parietal cortex at the acute phase of radiation
      induced brain injury using computed tomography (CT). METHODS: A rat model of
      brain injury was established by CT scanning. The expression of EBA and S100B in
      the parietal cortex was analyzed at different time points by immunohistochemistry
      (IHC) and western blotting. RESULTS: Significantly increased EBA expression was
      detected in the animals in the control group compared with the animals receiving
      CT radiation, which exhibited significantly reduced EBA levels within the vessel
      walls (F=33.29, p<0.05), particularly at day 3 after radiation. Both
      immunohistochemical staining and western blot analysis indicated that the
      positive expression levels of S100B among radiation groups were increased
      compared with the control group (IHC, F=28.05, p<0.05; WB, F=175.3, p<0.05). The
      expression of S100B peaked at day 3 (IHC, 102718+/-8710; WB, 2320+/-0.129), and
      subsequently decreased. CONCLUSION: CT radiation can induce altered EBA and S100B
      protein expression. Decreased EBA expression levels indicated that the integrity
      of the blood-brain barrier (BBB) was affected by radiation. The destruction of
      the BBB and the expression of S100B might play important roles in the incidence
      and repair of the early radiation-induced brain injury, and radiation represents
      a cause of mental disorders.

PMID- 24569095
TI  - The NBOMe hallucinogenic drug series: Patterns of use, characteristics of users
      and self-reported effects in a large international sample.
AB  - The NBOMe compounds are a novel series of hallucinogenic drugs that are potent
      agonists of the 5-HT2A receptor, have a short history of human consumption and
      are available to buy online, in most countries. In this study, we sought to
      investigate the patterns of use, characteristics of users and self-reported
      effects. A cross-sectional anonymous online survey exploring the patterns of drug
      use was conducted in 2012 (n = 22,289), including questions about the use of 25B
      NBOMe, 25C-NBOMe, and 25I-NBOMe and comparison drugs. We found that 2.6% of
      respondents (n = 582) reported having ever tried one of the three NBOMe drugs and
      that at 2.0%, 25I-NBOMe was the most popular (n = 442). Almost all (93.5%)
      respondents whose last new drug tried was a NBOMe drug, tried it in 2012, and
      81.2% of this group administered the drug orally or sublingually/buccally.
      Subjective effects were similar to comparison serotonergic hallucinogens, though
      higher 'negative effects while high' and greater 'value for money' were reported.
      The most common (41.7%) drug source was via a website. The NBOMe drugs have
      emerged recently, are frequently bought using the internet and have similar
      effects to other hallucinogenic drugs; however, they may pose larger risks, due
      to the limited knowledge about them, their relatively low price and availability
      via the internet. 

PMID- 24569096
TI  - A comparison of psychotropic medication prescribing patterns in East of England
      prisons and the general population.
AB  - While the prevalence of mental illness is higher in prisons than in the
      community, less is known about comparative rates of psychotropic medicine
      prescribing. This is the first study in a decade to determine the prevalence and
      patterns of psychotropic medication prescribing in prisons. It is also the first
      study to comprehensively adjust for age when making comparisons with the general
      population. Four East of England prisons, housing a total of 2222 men and 341
      women were recruited to the study. On census days, clinical records were used to
      identify and collect data on all prisoners with current, valid prescriptions for
      hypnotic, anxiolytic, antipsychotic, antimanic, antidepressant and/or stimulant
      medication, as listed in chapters 4.1 to 4.4 of the British National Formulary.
      Data on 280,168 patients were obtained for comparison purposes from the Clinical
      Practice Research Datalink. After adjusting for age, rates of psychotropic
      prescribing in prison were 5.5 and 5.9 times higher than in community-based men
      and women, respectively. We also found marked differences in the individual
      psychotropic drugs prescribed in prison and community settings. Further work is
      necessary to determine whether psychotropic prescribing patterns in prison
      reflect an appropriate balance between managing mental illness, physical health
      risks and medication misuse. 

PMID- 24569097
TI  - Initiating and developing clinical services, training and research in a low
      resource setting: the Malawi ENT experience.
AB  - BACKGROUND: Sub-Saharan Africa countries like Malawi have a paucity of ear, nose
      and throat (ENT) data, services and training opportunities. OBJECTIVE: To reflect
      on new Malawian ENT experience and to propose guidelines to poorly resourced
      countries. DESIGN: Analysis of data predating and following establishment of ENT
      services in Malawi. RESULTS: In 2008 the first and only Malawian ENT specialist
      established ENT services with external funding. Fifteen clinical officers have
      been trained and a nurse placed at each outreach hospital. In 2012, 15,284
      consultations were recorded: 543 (3.6%) from outreach clinics. Forty-nine percent
      needed medical treatment, while 45% needed medical advice. Surgery was performed
      on 2.7% of patients; 21% for foreign bodies in the nose and throat and 18% for
      foreign bodies and biopsies of ears. CONCLUSIONS: To establish accessible and
      sustainable specialist ENT services in a poor country requires building on an
      established local health delivery system, careful planning and investment in
      personnel, infrastructure, training and data collection.

PMID- 24569098
TI  - Myocardial injury following multiple bee stings.
AB  - Envenomation by the honey bee can cause multi-organ dysfunction as a result of
      toxic effects and may cause a severe anaphylactic reaction. Acute myocardial
      ischemia is an extremely rare complication of bee envenomation. We report a case
      of a 58-year-old woman with acute myocardial injury following massive bee
      envenomation. 

PMID- 24569099
TI  - Impact of once- versus twice-daily perphenazine dosing on clinical outcomes: an
      analysis of the CATIE data.
AB  - OBJECTIVE: The objective of this study was to evaluate the impact of once- versus
      twice-daily dosing of perphenazine, which has a plasma half-life of 8-12 hours,
      on clinical outcomes in patients with schizophrenia. METHOD: Data from phase 1 of
      the Clinical Antipsychotic Trial of Intervention Effectiveness (CATIE) conducted
      between January 2001 and December 2004 were used in this post hoc analysis.
      Patients with schizophrenia (DSM-IV) randomly allocated to treatment with
      perphenazine were also randomly assigned to once-daily (N = 133) or twice-daily
      (N = 124) dosing and followed over 18 months. Discontinuation rate and time to
      discontinuation were used as primary outcomes to compare the 2 groups. The
      following clinical outcomes were analyzed as secondary measures: efficacy
      Positive and Negative Syndrome Scale, Clinical Global Impressions-Severity scale,
      Calgary Depression Scale for Schizophrenia, and Drug Attitude Inventory and
      safety/tolerability-Abnormal Involuntary Movement Scale, Barnes Akathisia Rating
      Scale, Simpson-Angus Scale, and body weight. Data on treatment-emergent adverse
      events, concomitant psychotropic medications, and medication adherence (pill
      count and clinician rating scale) were also analyzed for each group. RESULTS: No
      significant differences were found in any outcome measures between the once-daily
      and twice-daily dosing groups, which remained the same when using the mean dose
      of perphenazine as a covariate. CONCLUSIONS: Perphenazine is routinely
      administered in a divided dosage regimen because of its relatively short plasma
      half-life. However, the present findings challenge such a strategy, suggesting
      that once-daily represents a viable treatment option. Results are discussed in
      the context of more recent evidence that challenges the need for high and
      continuous dopamine D2 receptor blockade to sustain antipsychotic response. TRIAL
      REGISTRATION: ClinicalTrials.gov identifier: NCT00014001.

PMID- 24569100
TI  - In silico assessment of the metabolic capabilities of an engineered functional
      reversal of the beta-oxidation cycle for the synthesis of longer-chain (C>=4)
      products.
AB  - The modularity and versatility of an engineered functional reversal of the beta
      oxidation cycle make it a promising platform for the synthesis of longer-chain
      (C>=4) products. While the pathway has recently been exploited for the production
      of n-alcohols and carboxylic acids, fully capitalizing on its potential for the
      synthesis of a diverse set of product families requires a system-level assessment
      of its biosynthetic capabilities. To this end, we utilized a genome scale model
      of Escherichia coli, in combination with Flux Balance Analysis and Flux
      Variability Analysis, to determine the key characteristics and constraints of
      this pathway for the production of a variety of product families under
      fermentative conditions. This analysis revealed that the production of n
      alcohols, alkanes, and fatty acids of lengths C3-C18 could be coupled to cell
      growth in a strain lacking native fermentative pathways, a characteristic
      enabling product synthesis at maximum rates, titers, and yields. While energetic
      and redox constraints limit the production of target compounds from alternative
      platforms such as the fatty acid biosynthesis and alpha-ketoacid pathways, the
      metabolic efficiency of a beta-oxidation reversal allows the production of a wide
      range of products of varying length and functionality. The versatility of this
      platform was investigated through the simulation of various termination pathways
      for product synthesis along with the use of different priming molecules,
      demonstrating its potential for the efficient synthesis of a wide variety of
      functionalized compounds. Overall, specific metabolic manipulations suggested by
      this systems-level analysis include deletion of native fermentation pathways, the
      choice of priming molecules and specific routes for their synthesis, proper
      choice of termination enzymes, control of flux partitioning at the pyruvate node
      and the pentose phosphate pathway, and the use of an NADH-dependent trans-enoyl
      CoA reductase instead of a ferredoxin-dependent enzyme. 

PMID- 24569101
TI  - Global species richness estimates have not converged.
AB  - We demonstrate that after more than six decades, estimates of global species
      richness have failed to converge, remain highly uncertain, and in many cases, are
      logically inconsistent. Convergence in these estimates could be accelerated by
      adaptive learning methods where the estimation of uncertainty is prioritised and
      used to guide future research. 

PMID- 24569102
TI  - The European Cancer Observatory: A new data resource.
AB  - Population-based cancer registries provide indispensable information on cancer
      incidence and survival, which cannot be obtained by any other means. It is clear
      that complete and effective use of these data is essential for cancer control,
      but sharing this information in a uniform, timely and user-friendly manner has
      been somewhat limited up to now. The European Cancer Observatory (ECO,
      http://eco.iarc.fr) has been developed in the framework of the EUROCOURSE project
      (EUROpe against Cancer: Optimisation of Use of Registries for Scientific
      Excellence in Research) as a comprehensive resource combining all the information
      currently available in Europe on cancer incidence, mortality, survival and
      prevalence. The website provides analytical and presentation tools to examine
      national estimates for 2012 in 40 European countries (EUCAN), data for 130
      national or sub-national areas covered by cancer registries for up to 60 years,
      until 2011 (EUREG) and a planned mechanism for data download (European Cancer
      Incidence and Mortality (EUROCIM)). The generated statistics outline the
      considerable variability across Europe in the rates of all major cancer types and
      help identify key concerns that need to be addressed by public health policies
      e.g. the unprecedented rise of lung cancer incidence in women with its full
      impact expected within a decade or so. The support, maintenance and further
      development of the ECO website should be a high priority for European cancer
      policymakers, to continue providing this unique information to health
      professionals, researchers and the general public in Europe and beyond.

PMID- 24569103
TI  - Clinical outcome of reconstruction with tissue expanders for patients with breast
      cancer and mastectomy.
AB  - BACKGROUND: Because the number of patients with breast cancer who have
      reconstruction after mastectomy is increasing, we analyzed the outcomes of
      reconstruction with tissue expanders (TEs). PATIENTS AND METHODS: From 2004 to
      2009, 133 patients with unilateral primary breast cancer who required mastectomy
      concurrent with reconstruction using TEs (TE group) and 308 patients with breast
      cancer who underwent mastectomy without reconstruction (MT group) were examined.
      RESULTS: The median follow-up period was 47 months versus 44 months (TE group vs.
      MT group, respectively). The median age was 46 years in the TE group and 58 years
      in the MT group (P < .0001). The rate of hormone receptor positivity in the TE
      group was significantly higher than in the MT group (P = .0123). The incidence of
      local recurrence, time to detection of local recurrence, and size of tumor in
      local recurrence in the TE group and the MT group were 3.8% versus 1.6% (P =
      .1560), 17.2 months versus 12.4 months (P = .9166), and 1.9 cm versus 2.4 cm (P =
      .6742), respectively. In the TE versus the MT groups, relapse-free survival (RFS)
      and overall survival (OS) at 45 months were 89.0% versus 87.9% (P = .8706) and
      93.9% versus 94.2% (P = .9947), respectively. The incidence of infection was
      significantly higher in the TE group than in the MT group-14.3 % versus 2.9%,
      respectively (P < .0001). CONCLUSION: Compared with mastectomy alone, immediate
      reconstruction with TEs did not impair prognosis or contribute to a delay in
      detection of local recurrence, although the incidence of surgical site infection
      in the TE group was significantly higher than in the MT group.

PMID- 24569104
TI  - Individual patterns of alcohol use.
AB  - AIMS: We present methodology to identify statistically distinct patterns of daily
      alcohol use and classify them into categories that could be further used in
      monitoring of transitions between patterns such as transitions from regular to
      problem use. DATA: The study analyzed individual patterns of adult alcohol
      consumption from two datasets containing short (<6 month) and long (up to 2years)
      daily records of drinking. These data were collected over the period between 1999
      and 2003. RESULTS: By using a non-parametric (Kolmogorov-Smirnov) test we have
      identified distinct drinking patterns and classified them into 8 types according
      to their means, percentages of non-drinking days and variances of consumed amount
      during drinking days. For each studied individual we calculated a transition
      chart that characterizes transitions between the types. CONCLUSIONS: Individual
      daily consumption patterns can be identified, and classified into distinct
      patterns. Changes between the patterns could be related to life events or
      environmental trends, and thus provide insights into pathways towards either
      heavier use or recovery.

PMID- 24569105
TI  - mTOR limits the recruitment of CD11b+Gr1+Ly6Chigh myeloid-derived suppressor
      cells in protecting against murine immunological hepatic injury.
AB  - The mTOR pathway integrates diverse environmental inputs, including immune
      signals and metabolic cues, to direct the innate and adaptive immune responses.
      MDSCs are a heterogeneous cell population that plays a crucial regulatory effect
      in immune-related diseases. However, whether mTOR signaling affects the functions
      of MDSCs remains largely unknown. Here, we show that mTOR signaling is a pivotal
      negative determinant of MDSC recruitment in IMH disease. In the context of IMH,
      inhibition of mTOR with rapamycin in CD11b+Gr1+ MDSCs mediates protection against
      IMH and serves as a functional, suppressive immune modulator that results in
      increased CD11b+Gr1+Ly6C(high) MDSC recruitment to inflammatory sites. In
      agreement with this, mTOR down-regulation promotes CD11b+Gr1+Ly6C(high) MDSC
      migration in vitro and in vivo. Mechanistically, mTOR activity down-regulation in
      MDSCs induced iNOS expression and NO production. Pharmacologic inhibition of iNOS
      completely eliminated MDSC recruitment. This study identifies MDSCs as an
      essential component for protection against IMH following rapamycin treatment.
      Rapamycin treatment or mTOR inhibition promotes CD11b+Gr1+Ly6C(high) MDSC
      recruitment and is critically required for protection against hepatic injury.
      This study further validates the targeting of mTOR signaling as a potential
      therapeutic approach to IMH-related diseases.

PMID- 24569106
TI  - Small-scale early aggregation of green tide macroalgae observed on the Subei
      Bank, Yellow Sea.
AB  - Massive green algae blooms became an environmental disaster in the Yellow Sea
      from 2008 to 2013. Recent studies suggested that recurrences of early aggregates
      of macroalgae were found over the Subei Bank, a unique shallow radial sand ridge
      system off the Jiangsu coast, China. Yearly field surveys have been carried out
      over this bank during the past five years (2009-2013), with an aim at identifying
      and qualifying the physical-biological mechanism for the early aggregation of
      algae. Data synthesis showed that early aggregation of macroalgae usually
      occurred from April-May as small-scale patches either over the intertidal mudflat
      of the Subei Bank or along local isobaths in the northern coastal area north of
      the bank. Both hydrographic and current measurements were performed by tracking a
      narrow patchy area of floating macroalgae (nearly 4 km in length and 5-10 m in
      width) on April 26, 2013, and the results showed that the algae aggregation was
      mainly caused by tide-induced convergence. This convergence was produced by the
      local geometrically controlled interaction of tidal currents with mudflats, which
      is believed to be a key physical mechanism for the early development of algal
      blooms in addition to marine ecosystem responses and human aquaculture
      activities.

PMID- 24569107
TI  - Effect of nanopyramid bottom electrodes on bipolar resistive switching phenomena
      in nickel nitride films-based crossbar arrays.
AB  - The improved resistive switching (RS) performance characteristics of nickel
      nitride (NiN) films-based crossbar array (CBA) memory resistors-such as reduction
      in the operating voltages, reset current and current/voltage variations; no
      initial forming process; and set/reset speeds--are demonstrated using nanopyramid
      patterned (NPP) platinum-bottom electrodes. Compared with a conventional CBA
      sample with flat-bottom electrodes, both the voltage and the current of the set
      and reset operations are respectively reduced when NPP samples are used. The
      drastic reduction in the variation of the operating voltage and current is of
      particular interest. We explain the RS process using the model of the redox
      reaction-mediated formation and rupture of the conducting filaments in the NiN
      films, based on the capacitance-voltage and conductance-voltage characteristics
      under different resistance states.

PMID- 24569108
TI  - Probable longer incubation period for human infection with avian influenza
      A(H7N9) virus in Jiangsu Province, China, 2013.
AB  - Human infection with the emerging avian influenza A(H7N9) virus in China in 2013
      has raised global concerns. We conducted a retrospective descriptive study of 27
      confirmed human influenza A(H7N9) cases in Jiangsu Province, to elaborate poultry
      related exposures and to provide a more precise estimate of the incubation
      periods of the illness. The median incubation period was 6 days (range 2-10 days)
      in cases with single known exposure and was 7.5 days (range 6.5-12.5 days) in
      cases with exposures on multiple days, difference between the two groups was not
      significant (Z = -1.895, P = 0.058). The overall median incubation period for all
      patients was estimated to be 7.5 days (range 2-12.5 days). Our findings further
      highlight the necessity for public health authorities to extend the period of
      medical surveillance from 7 days to 10 days.

PMID- 24569109
TI  - Prevalence of psoriasis in Spain in the age of biologics.
AB  - INTRODUCTION: The prevalence of psoriasis in Spain was estimated to be 1.4%
      before the advent of biologic agents. Fifteen years later, new therapeutic
      options based on biologic agents have led to greater awareness of the disease and
      better understanding; case detection and diagnosis may have improved as a result.
      OBJECTIVE: To investigate the current prevalence of psoriasis in Spain and
      compare the results with those of an earlier study that used the same
      methodology. MATERIAL AND METHODS: Population-based cross-sectional survey.
      Information was collected through computer-assisted telephone interviews with a
      randomly selected representative sample of the Spanish population (12,711
      individuals from 4,754 households). Interviews were conducted by trained
      personnel using a questionnaire. RESULTS: The prevalence was 2.3% and there were
      no statistically significant differences between the sexes. Prevalence increased
      with age (range with highest prevalence, 60-69 years). Central Spain-a region
      with a cold, dry climate-had the highest prevalence, but differences between
      regions were not significant. CONCLUSIONS: Psoriasis is substantially more
      prevalent in Spain than was previously estimated. The increase in prevalence may
      reflect greater awareness and better diagnosis of the disease rather than a true
      increase in number of cases.

PMID- 24569110
TI  - Discovery of dual ZAP70 and Syk kinases inhibitors by docking into a rare C-helix
      out conformation of Syk.
AB  - The non-receptor tyrosine kinase Syk (spleen tyrosine kinase) is a pharmaceutical
      relevant target because its over-activation is observed in several autoimmune
      diseases, allergy, and asthma. Here we report the identification of two novel
      inhibitors of Syk by high-throughput docking into a rare C-helix-out conformation
      published recently. Interestingly, both compounds are slightly more active on
      ZAP70 (Zeta-chain-associated protein kinase 70), which is the kinase closest to
      Syk in the phylogenetic tree of human kinases. Taken together, the docking pose
      and experimental results suggest that the higher affinity of the inhibitors for
      ZAP70 than Syk originates from a more populated C-helix-out conformation in
      ZAP70. The latter observation is congruent with the 100-fold lower intrinsic
      activity of ZAP70 than Syk, as the C-helix-out conformation is inactive. The
      pharmacophore features of DFG-in, C-helix-out compounds are analyzed in relation
      to DFG-out inhibitors. 

PMID- 24569111
TI  - Synthesis and pharmacological evaluation of novel limonin derivatives as anti
      inflammatory and analgesic agents with high water solubility.
AB  - A novel series of water-soluble derivatives of limonin were synthesized by
      introducing various tertiary amines onto the C (7)-position of limonin. Ten
      target compounds were characterized and screened for their anti-inflammatory and
      analgesic activity in vivo. Compound 3c exhibited the strongest analgesic and
      anti-inflammatory activity among the limonin and its derivatives tested; its
      analgesic activity is more potent than that of aspirin and its anti-inflammatory
      activity is stronger than that of naproxen. 

PMID- 24569112
TI  - Microbubble-mediated sonoporation amplified lipid peroxidation of Jurkat cells.
AB  - Sonoporation is a developing technique used in drug delivery for cancer cells.
      Low frequency ultrasound is used to trigger the cavitation of microbubbles to
      puncture the cell membrane, and during this process, lipid metabolism becomes
      disrupted. In this study, cell viability and the generation of specific oxidized
      lipid products were assessed in Jurkat cells before and after sonoporation. A
      reduction in cell viability and an induction of apoptosis of Jurkat cells were
      found 4 h and 24 h post-sonoporation, respectively. Sonoporation suppressed
      cholesterol concentration and arachidonic, eicosapentaenoic and docosahexaenoic
      acids in the Jurkat cells. Levels of enzyme-independent oxidized products (F2
      isoprostanes, F3-isoprostanes, 7-ketocholesterol) were elevated by sonoporation
      compared with the control, whereas enzyme-dependent oxidized products (5(S)-,
      9(S)-, 12(S)-, 15(S)- and 20-HETE and 27-hydroxycholesterol) were not altered.
      Antioxidant enzymes activities were also increased in sonoporated Jurkat cells
      compared with the control. In this study, the loss of lipids potentially
      increased the availability for enzyme-independent lipid peroxidation, leading to
      cell fragility and death.

PMID- 24569113
TI  - Endovascular stent graft repair of thoracic aortic mural thrombus in a patient
      with polycythemia vera: a word of caution.
AB  - Thoracic aortic mural thrombus (TAMT) is a rare pathology and potential source of
      cerebral, visceral, and peripheral emboli. We present a 62-year-old male in a
      hypercoagulable state due to primary polycythemia vera (PV) developed TAMT and
      catastrophic thromboembolisms despite aggressive medical and surgical management.
      The outcomes and adverse events of endovascular exclusion of TAMT in the presence
      of PV are unknown. We would recommend proceeding with extreme caution when
      performing endovascular exclusion of TAMT, as PV may be a prohibitive risk. 

PMID- 24569114
TI  - Increased serum levels of interleukin 33 in patients with atopic dermatitis.
AB  - BACKGROUND: Interleukin (IL)-33 is a new member of the IL-1 cytokine family and a
      promoter of T helper type 2 (Th2) inflammation. IL-33 may be involved in the
      pathogenesis of atopic dermatitis (AD), but its relationship with disease
      severity, laboratory markers, and eruption types in patients with AD are unclear.
      OBJECTIVE: The aim of this study was to quantify serum IL-33 levels in patients
      with AD and to examine relationships with disease severity, laboratory markers,
      and eruption types. METHODS: Serum IL-33 was measured by enzyme-linked
      immunosorbent assay in patients with AD, chronic idiopathic urticaria, and
      psoriasis and in healthy control subjects. RESULTS: Serum levels of IL-33 were
      significantly higher in patients with AD compared with those in patients with
      urticaria and psoriasis and in healthy control subjects, and were correlated with
      the disease severity of AD. IL-33 levels were also significantly correlated with
      excoriation and xerosis scores, but not with blood eosinophilia, serum IgE, serum
      thymus and activation-related chemokine, and serum lactate dehydrogenase.
      Elevated IL-33 levels were significantly reduced after improvement of skin
      lesions by drug treatment. LIMITATION: A limitation in the study was the small
      number of subjects. CONCLUSION: Our results suggest that IL-33 released from
      mechanically injured or barrier-disrupted skin may increase inflammation in AD.

PMID- 24569115
TI  - Association of lichen planopilaris with thyroid disease: a retrospective case
      control study.
AB  - BACKGROUND: Studies on the precise causes and comorbidities seen with lichen
      planopilaris (LPP) are limited. OBJECTIVE: We sought to determine the prevalence
      of thyroid diseases in patients with LPP. METHODS: Medical records of 166
      patients with LPP and 81 age- and gender-matched control subjects seen in the
      Department of Dermatology at the Cleveland Clinic Foundation in Ohio between 2000
      and 2013 were reviewed. RESULTS: A diagnosis of thyroid disease was present in
      34% (n = 57) of the 166 patients with LPP, and in 11% (n = 9) of the control
      subjects (P = .0001). When confined to hypothyroidism only, this disease was
      found in 29% (n = 48) of the patients with LPP and 9% (n = 7) of the control
      subjects (P = .0003). LIMITATIONS: This study was limited by being retrospective.
      CONCLUSION: In our patients, LPP was associated with thyroid disease, especially
      hypothyroidism.

PMID- 24569116
TI  - Malassezia infections: a medical conundrum.
AB  - Malassezia yeasts have long been considered commensal fungi, unable to elicit
      significant damage. However, they have been associated with a diversity of
      cutaneous diseases, namely pityriasis versicolor, Malassezia folliculitis,
      seborrheic dermatitis, atopic dermatitis, psoriasis, and confluent and reticulate
      papillomatosis. Several hypotheses have been proposed to explain the pathogenic
      mechanisms of these fungi, but none have been confirmed. More recently, such
      organisms have been increasingly isolated from bloodstream infections raising
      serious concern about these fungi. Given the difficulty to culture these yeasts
      to proceed with speciation and antimicrobial susceptibility tests, such
      procedures are most often not performed and the cutaneous infections are treated
      empirically. The recurring nature of superficial skin infections and the
      potential threat of systemic infections raise the need of faster and more
      sensitive techniques to achieve isolation, identification, and antimicrobial
      susceptibility profile. This article reviews and discusses the latest available
      data concerning Malassezia infections and recent developments about diagnostic
      methods, virulence mechanisms, and susceptibility testing. 

PMID- 24569117
TI  - Cx26 regulates proliferation of repairing basal airway epithelial cells.
AB  - The recovery of an intact epithelium following injury is critical for restoration
      of lung homeostasis, a process that may be altered in cystic fibrosis (CF). In
      response to injury, progenitor cells in the undamaged areas migrate, proliferate
      and re-differentiate to regenerate an intact airway epithelium. The mechanisms
      regulating this regenerative response are, however, not well understood. In a
      model of circular wound injury of well-differentiated human airway epithelial
      cell (HAEC) cultures, we identified the gap junction protein Cx26 as an important
      regulator of cell proliferation. We report that induction of Cx26 in repairing
      HAECs is associated with cell proliferation. We also show that Cx26 is expressed
      in a population of CK14-positive basal-like cells. Cx26 silencing in immortalized
      cell lines using siRNA and in primary HAECs using lentiviral-transduced shRNA
      enhanced Ki67-labeling index and Ki67 mRNA, indicating that Cx26 acts a negative
      regulator of HAEC proliferation. Cx26 silencing also markedly decreased the
      transcription of KLF4 in immortalized HAECs. We further show that CF HAECs
      exhibited deregulated expression of KLF4, Ki67 and Cx26 as well enhanced rate of
      wound closure in the early response to injury. These results point to an altered
      repair process of CF HAECs characterized by rapid but desynchronized initiation
      of HAEC activation and proliferation.

PMID- 24569118
TI  - MITOCHONDRIA: investigation of in vivo muscle mitochondrial function by 31P
      magnetic resonance spectroscopy.
AB  - The most important function of mitochondria is the production of energy in the
      form of ATP. The socio-economic impact of human diseases that affect skeletal
      muscle mitochondrial function is growing, and improving their clinical management
      critically depends on the development of non-invasive assays to assess
      mitochondrial function and monitor the effects of interventions. 31P magnetic
      resonance spectroscopy provides two approaches that have been used to assess in
      vivo ATP synthesis in skeletal muscle: measuring Pi->ATP exchange flux using
      saturation transfer in resting muscle, and measuring phosphocreatine recovery
      kinetics after exercise. However, Pi->ATP exchange does not represent net
      mitochondrial ATP synthesis flux and has no simple relationship with
      mitochondrial function. Post-exercise phosphocreatine recovery kinetics, on the
      other hand, yield reliable measures of muscle mitochondrial capacity in vivo,
      whose ability to define the site of functional defects is enhanced by combination
      with other non-invasive techniques.

PMID- 24569119
TI  - Alternative macroautophagy and mitophagy.
AB  - Mitophagy is a mitochondrial quality control mechanism where damaged and surplus
      mitochondria are removed by macroautophagy. Mitophagy is associated with various
      physiological and pathological events such as mitochondrial clearance during
      terminal differentiation of reticulocytes. There are two different mammalian
      macroautophagy pathways: the Atg5-dependent conventional pathway and an Atg5
      independent alternative pathway; the latter is involved in the erythrocyte
      mitophagy. 

PMID- 24569121
TI  - Mitochondria: biological roles in platelet physiology and pathology.
AB  - Mitochondria are key regulators of cellular energy and redox metabolism, also
      playing a central role in cell signaling and death pathways. A number of
      processes occur within mitochondria, including redox-dependent ATP synthesis by
      oxidative phosphorylation and reactive oxygen species production. Mitochondrial
      permeability transition is a reversible process that may lead to cell death and
      is regulated by calcium and reactive oxygen species. Functional mitochondria are
      present in platelets, and evidence has demonstrated the direct involvement of
      these organelles in cellular ATP production, redox balance, as well as in
      platelet activation and apoptosis. Here, we review aspects of platelet physiology
      in which mitochondria are involved, as well as assess their function as new tools
      for studying a number of human diseases. 

PMID- 24569120
TI  - Integrated transcriptome analysis across mitochondrial disease etiologies and
      tissues improves understanding of common cellular adaptations to respiratory
      chain dysfunction.
AB  - Mitochondrial diseases are heterogeneous, multi-systemic disorders for which
      mechanistic understanding is limited. To investigate common downstream effects of
      primary respiratory chain dysfunction on global gene expression and pathway
      regulation, we reanalyzed transcriptome datasets from all publicly available
      studies of respiratory chain dysfunction resulting from genetic disorders, acute
      pathophysiologic processes, or environmental toxins. A general overview is
      provided of the bioinformatic processing of transcriptome data to uncover
      biological insights into in vivo and in vitro adaptations to mitochondrial
      dysfunction, with specific examples discussed from a variety of independent cell,
      animal, and human tissue studies. To facilitate future community efforts to
      cohesively mine these data, all reanalyzed transcriptome datasets were deposited
      into a publicly accessible central web archive. Our own integrated meta-analysis
      of these data identified several commonly dysregulated genes across diverse
      mitochondrial disease etiologies, models, and tissue types. Overall,
      transcriptome analyses provide a useful means to survey cellular adaptation to
      mitochondrial diseases. 

PMID- 24569122
TI  - Lung disease modifier genes in cystic fibrosis.
AB  - Cystic fibrosis (CF) is recognized as a single gene disorder. However, a
      considerable diversity in its clinical phenotype has been documented since the
      description of the disease. Identification of additional gene alleles, so called
      "modifier genes" that directly influence the phenotype of CF disease became a
      challenge in the late '90ies, not only for the insight it provides into the CF
      pathophysiology, but also for the development of new potential therapeutic
      targets. One of the most studied phenotype has been the lung disease severity as
      lung dysfunction is the major cause of morbidity and mortality in CF. This review
      details the results of two main genetic approaches that have mainly been explored
      so far: (1) an "a priori" approach, i.e. the candidate gene approach; (2) a
      "without a priori" approach, analyzing the whole genome by linkage and genome
      wide association studies (GWAS), or the whole exome by exome sequencing.

PMID- 24569123
TI  - Loss of Calbindin immunoreactivity in the dentate gyrus distinguishes Alzheimer's
      disease from other neurodegenerative dementias.
AB  - Calbindin (Cb) is one of the major Ca(2+) binding proteins exhibiting
      neuromodulatory functions such as long-term potentiation (LTP), synaptic
      plasticity, and memory functions. It is expressed in hippocampal interneurons,
      pyramidal cells and granule cells of the dentate gyrus (DGCs). Cb mRNA levels
      remain stable during normal ageing, but decrease in Alzheimer's, Huntington, and
      Parkinson's disease. A recent study suggested a link between Abeta-induced
      Alzheimer's disease (AD)-related cognitive deficits and neuronal depletion of Cb.
      To evaluate whether this is specific for AD, we performed a comparative study of
      Cb immunoreactivity of DGCs in cases with AD-related neuropathologic change (49),
      grouped according to the stages of Braak and Braak, BB), Creutzfeldt-Jakob
      disease (16), FTLD-tau Pick's disease type (PiD; 5), argyrophilic grain disease
      (8), and FTLD-TDP types A and B (6). The group of AD cases with BB stages V and
      VI showed the highest proportion of Cb negative cells in the DGC when compared to
      all other groups except PiD. The ratio of negative cells correlated significantly
      with the BB stages. While the total number of DGCs decreased with age in our
      series, loss of Cb immunoreactivity was shown to be age-dependent only in PiD and
      FTLD-TDP. We conclude, that late stage AD-neuropathologic change (BB V and VI
      stages) associates with significantly higher ratios of Cb negative DGCs and this
      correlates with advanced BB stage. This might suggest an accumulative effect of
      an epilepsy-like pathway on the Cb expression or the direct influence of local
      pathological protein deposits on the DGCs. 

PMID- 24569124
TI  - Characterization of CO2 and mixed methane/CO2 hydrates intercalated in smectites
      by means of atomistic calculations.
AB  - The recent increase in anthropogenic CO2 gas released to the atmosphere and its
      contribution to global warming make necessary to investigate new ways of CO2
      storage. Injecting CO2 into subsurface CH4 hydrate reservoirs would displace some
      of the CH4 in the hydrate crystal lattice, converting simple CH4 hydrates into
      either simple CO2 hydrates or mixed CH4CO2 hydrates. Molecular simulations were
      performed to determine the structure and behavior of CO2 and mixed hydrate
      complexes in the interlayer of Na-rich montmorillonite and beidellite smectite.
      Molecular Dynamics (MD) simulations used NPT ensembles in a 4*4*1 supercell
      comprised of montmorillonite or beidellite with CO2 or mixed CH4/CO2 hydrate
      complexes in the interlayer. The smectite 2:1 layer surface helps provide a
      stabilizing influence on the formation of gas hydrate complexes. The type of
      smectite affects the stability of the smectite-hydrate complexes, where high
      charge located on the tetrahedral layer of the smectites disfavor the formation
      of hydrate complexes. 

PMID- 24569126
TI  - Fabrication of solution processed 3D nanostructured CuInGaS2 thin film solar
      cells.
AB  - In this study we demonstrate the fabrication of CuInGaS2 (CIGS) thin film solar
      cells with a three-dimensional (3D) nanostructure based on indium tin oxide (ITO)
      nanorod films and precursor solutions (Cu, In and Ga nitrates in alcohol). To
      obtain solution processed 3D nanostructured CIGS thin film solar cells, two
      different precursor solutions were applied to complete gap filling in ITO
      nanorods and achieve the desirable absorber film thickness. Specifically, a
      coating of precursor solution without polymer binder material was first applied
      to fill the gap between ITO nanorods followed by deposition of the second
      precursor solution in the presence of a binder to generate an absorber film
      thickness of ~1.3 MUm. A solar cell device with a (Al, Ni)/AZO/i-ZnO/CdS/CIGS/ITO
      nanorod/glass structure was constructed using the CIGS film, and the highest
      power conversion efficiency was measured to be ~6.3% at standard irradiation
      conditions, which was 22.5% higher than the planar type of CIGS solar cell on ITO
      substrate fabricated using the same precursor solutions.

PMID- 24569125
TI  - Clinical practice guideline on diagnosis and treatment of hyponatraemia.
AB  - Hyponatraemia, defined as a serum sodium concentration <135 mmol/l, is the most
      common disorder of body fluid and electrolyte balance encountered in clinical
      practice. It can lead to a wide spectrum of clinical symptoms, from subtle to
      severe or even life threatening, and is associated with increased mortality,
      morbidity and length of hospital stay in patients presenting with a range of
      conditions. Despite this, the management of patients remains problematic. The
      prevalence of hyponatraemia in widely different conditions and the fact that
      hyponatraemia is managed by clinicians with a broad variety of backgrounds have
      fostered diverse institution- and speciality-based approaches to diagnosis and
      treatment. To obtain a common and holistic view, the European Society of
      Intensive Care Medicine (ESICM), the European Society of Endocrinology (ESE) and
      the European Renal Association - European Dialysis and Transplant Association
      (ERA-EDTA), represented by European Renal Best Practice (ERBP), have developed
      the Clinical Practice Guideline on the diagnostic approach and treatment of
      hyponatraemia as a joint venture of three societies representing specialists with
      a natural interest in hyponatraemia. In addition to a rigorous approach to
      methodology and evaluation, we were keen to ensure that the document focused on
      patient-important outcomes and included utility for clinicians involved in
      everyday practice. 

PMID- 24569127
TI  - Active vitamin D analogs, maxacalcitol and alfacalcidol, as maintenance therapy
      for mild secondary hyperparathyroidism in hemodialysis patients - a randomized
      study.
AB  - BACKGROUND: The present randomized study was designed to compare the efficacy
      between two active vitamin D analogs, alfacalcidol (ACD) and maxacalcitol (OCT),
      for the management of mild secondary hyperparathyroidism (SHPT) in dialysis
      patients. METHODS: SHPT in all 32 patients analyzed in the study was initially
      treated with OCT. Once patients' intact PTH levels decreased to the target range
      of 150 - 180 pg/mL, they were randomized either to switch to ACD at 0.5 MUg/day
      (n = 14), or to remain on an effectively unchanged dose of OCT (n = 13).
      Phosphate, calcium, and intact PTH levels were measured every 2 weeks for 12
      weeks and vitamin D doses were changed according to target ranges of phosphate
      (3.5 - 6.0 mg/dL), calcium (albuminadjusted calcium: 8.4 - 10.0 mg/dL), and
      intact parathyroid hormone (60 - 180 pg/mL). Achievement rates of the target
      ranges of the parameters were estimated. RESULTS: Baseline calcium levels in the
      OCT group were significantly higher than in the ACD group. Changes in achievement
      rates of target ranges of intact PTH and calcium during the study did not differ
      significantly between the vitamin D drugs. Changes in calcium levels in the OCT
      and ACD groups were similar during the study. Achievement rates of the target
      range of phosphate in both groups were also similar until 8 weeks, although the
      rate in the OCT group declined at 10 weeks. CONCLUSIONS: The efficacy and safety
      of OCT for the treatment of mild SHPT are similar to those of ACD in hemodialysis
      patients.

PMID- 24569128
TI  - Zopiclone induced methemoglobinemia and hemolytic anemia.
AB  - OBJECTIVE: To characterize the risk of methemoglobinemia and hemolytic anemia
      following large overdoses of zopiclone, a cyclopyrrolone hypnotic-sedative and a
      racemic mixture of R-zopiclone and S-zopiclone (eszopiclone). METHODS: This
      review included all reports of zopiclone induced methemoglobinemia, hemolytic
      anemia, and oxidative stress that had been published in medical journals or
      discussed in continuous medical education (CME) programs. These reports were
      identified by searching the Medline (1980 - December 9, 2013), China Journal Net
      (1994 - December 2013), and Google Scholar, using zopiclone, eszopiclone,
      methemoglobinemia, hemolytic anemia, and oxidative stress as the search terms.
      RESULTS: Six cases of methemoglobinemia, one case of methemoglobinemia, with
      concomitant hemolytic anemia, and one case of hemolytic anemia were identified.
      These complications occurred after large zopiclone overdoses (450 - 3,750, 1,125 
      1,500, and 375 - 750 mg, respectively, i.e., 60 - 500, 150 - 200, and 50 - 100
      times the daily dose of 7.5 mg). The resulting methemoglobinemia could be severe
      (19.4 - 24.5%), while the hemolytic anemia was mild (Hb 9.0 - 9.6 g/dL).
      Molecular modelling analyses indicate that eszopiclone and its two metabolites
      will be kinetically labile. Their molecular surfaces have significant amounts of
      electron-deficient regions. All three compounds are expected to react with
      cellular nucleophiles, such as glutathione, causing its depletion and oxidative
      stress. CONCLUSIONS: After large overdoses, zopiclone, alone or together with its
      metabolites, most probably causes oxidative stress in erythrocytes to account for
      the methemoglobinemia and hemolytic anemia. Further studies are required to
      determine their incidence and the dose-related capacity of zopiclone and its
      metabolites in producing erythrocyte oxidative stress.

PMID- 24569129
TI  - Effect of dual bronchodilation with QVA149 on cardiac safety in healthy
      volunteers.
AB  - OBJECTIVES: QVA149 is a dual bronchodilator, containing a fixed-dose combination
      of the long-acting beta2-agonist indacaterol and long-acting muscarinic
      antagonist glycopyrronium, for the treatment of chronic obstructive pulmonary
      disease (COPD). Here we assess the potential of QVA149 (440/200 MUg) at 4-fold
      the therapeutic dose for causing cardiac pharmacodynamic (PD) effects. METHODS:
      This double-blind, randomized study estimated the time-matched largest heart rate
      (HR) change and average HR change (over 24 hours) from baseline for QVA149 vs.
      placebo in healthy subjects. Similar analyses were done for QVA149 vs.
      indacaterol 600 MUg, glycopyrronium 200 MUg, and salmeterol 200 MUg. The time
      matched and average change from baseline in QT interval corrected for HR using
      Fridericia's formula (QTcF), effects on serum potassium and blood glucose,
      pharmacokinetic (PK) parameters, and safety were also assessed. RESULTS: Of 50
      subjects randomized, 43 completed the study. QVA149, when compared with placebo,
      showed the time-matched largest mean increase and decrease in HR of 5.69 bpm and 
      2.51 bpm, respectively, and average HR change from baseline of 0.62 bpm. QVA149
      showed no tachycardic potential compared with indacaterol and no relevant
      tachycardic effect compared with glycopyrronium. No consistent differences were
      seen in the time-matched largest mean change and average change from baseline in
      QTcF for QVA149 vs. other treatments. There were no relevant effects of QVA149 on
      serum potassium and blood glucose. There was no apparent PK/PD relationship
      between the observed exposures to indacaterol and glycopyrronium in QVA149 on HR
      and QTcF. There were no deaths or serious adverse events. CONCLUSION: Overall,
      short-term administration of QVA149 showed a good cardiovascular safety and
      tolerability profile in healthy subjects.

PMID- 24569130
TI  - Pilot Trial of an Electronic Family Medical History in US Faith-Based
      Communities.
AB  - In spite of the acknowledged importance of collecting family health information,
      methods of collecting, organizing, and storage of pedigree data are not uniformly
      utilized in practice, though several electronic tools have been developed for the
      purpose. Using electronic tools to gather health information may empower
      individuals to take responsibility in managing their family health history. The
      purpose of this study was to describe the feasibility and outcomes of introducing
      small groups to the My Family Health Portrait tool in faith-based communities
      using faith community nurses (FCNs). This pilot project adopted a mixed methods
      approach to assess the potential of an educational intervention delivered by FCNs
      for increasing the use of electronic technologies for organizing and storing
      family health histories among the general public. Treatment and control groups
      were recruited from four faith-based communities in north Texas using a parallel
      groups quasi-experimental design. Qualitative data were gleaned from field notes
      made by investigators interacting with FCNs and observing their teaching. A
      majority of respondents believed that knowing one's health history and passing it
      on to family and medical personnel is important. Those receiving face-to-face
      instruction on the electronic tool were significantly more likely to have written
      down family health information than the control group who received only an
      informational handout (chi(2) = 5.96, P = .015). Barriers to teaching about and
      using the electronic tool included FCNs' lack of facility with computers in the
      educational context and FCN and respondent mistrust of electronic storage for
      family health information. 

PMID- 24569131
TI  - D53: the missing link in strigolactone signaling.

PMID- 24569132
TI  - Homotypic vacuole fusion requires VTI11 and is regulated by phosphoinositides.
AB  - Most plant cells contain a large central vacuole that is essential to maintain
      cellular turgor. We report a new mutant allele of VTI11 that implicates the SNARE
      protein VTI11 in homotypic fusion of protein storage and lytic vacuoles. Fusion
      of the multiple vacuoles present in vti11 mutants could be induced by treatment
      with Wortmannin and LY294002, which are inhibitors of Phosphatidylinositol 3
      Kinase (PI3K). We provide evidence that Phosphatidylinositol 3-Phosphate
      (PtdIns(3)P) regulates vacuole fusion in vti11 mutants, and that fusion of these
      vacuoles requires intact microtubules and actin filaments. Finally, we show that
      Wortmannin also induced the fusion of guard cell vacuoles in fava beans, where
      vacuoles are naturally fragmented after ABA-induced stomata closure. These
      results suggest a ubiquitous role of phosphoinositides in vacuole fusion, both
      during the development of the large central vacuole and during the dynamic
      vacuole remodeling that occurs as part of stomata movements. 

PMID- 24569133
TI  - Altered reproductive behaviours in male mosquitofish living downstream from a
      sewage treatment plant.
AB  - Freshwater environments are common repositories for the discharge of large
      volumes of domestic and industrial waste, particularly through wastewater
      effluent. One common group of chemical pollutants present in wastewater are
      endocrine disrupting chemicals (EDCs), which can induce morphological and
      behavioural changes in aquatic organisms. The aim of this study was to compare
      the reproductive behaviour and morphology of a freshwater fish, the mosquitofish
      (Gambusia holbrooki), collected from two sites (wastewater treatment plant (WWTP)
      and a putative pristine site). The mosquitofish is a sexually dimorphic
      livebearer with a coercive mating system. Males inseminate females using their
      modified anal fin as an intromittent organ. Despite this, females are able to
      exert some control over the success of male mating attempts by selectively
      associating with, or avoiding, certain males over others. Using standard
      laboratory assays of reproductive behaviour, we found that mosquitofish males
      living in close proximity to WWTP showed increased mating activity compared to
      those inhabiting a pristine site. More specifically, during behavioural trials in
      which males were allowed to interact with females separated by a transparent
      divider, we found that WWTP-males spent more time associating with females.
      Concordant with this, when males and females were subsequently allowed to
      interact freely, WWTP-males also spent more time chasing and orienting towards
      the females. As a result, females from both sites showed more interest towards
      the WWTP-site males. Male anal fin morphology, however, did not differ between
      sites. Our study illustrates that lifetime exposure to WWTP-effluents can greatly
      affect male behaviour. The results underscore the importance of behaviour as a
      potential tool for investigating unknown contaminants in the environment.

PMID- 24569134
TI  - Modified seromuscular patch flap for reinforcing an anastomosis site in
      hypopharyngeal reconstruction using free jejunal transfer: an anatomical and
      clinical study.
AB  - INTRODUCTION: Free jejunal transfer is commonly used as a reliable reconstructive
      method after total pharyngolaryngectomy. An anastomotic fistula is the most
      common complication in the early postoperative period, occurring in 5% to 35% of
      cases. There have been several studies regarding surgical techniques for
      minimizing fistula formation. Specifically, the vascularized seromuscular patch
      flap has been used for reinforcing the anastomosis site; however, this flap does
      not yield a sufficient range of motion because of traction on the vascular
      pedicle. METHODS: Between 2004 and 2011, 4 patients underwent vascularized
      seromuscular patch flaps with free jejunal transfer. A short segment of jejunum
      on a mesenteric pedicle is usually opened longitudinally along the antimesenteric
      border to make a patch flap; however, we made a longitudinal incision along 1
      side of the mesenteric border. To investigate the vascular anatomy of the flap, a
      lead oxide-gelatin mixture was injected into the arterial system of 4 fresh
      cadavers. RESULTS: The flap had increased mobility without traction on the
      vascular pedicle and adequate circulation. In the injection study, it was shown
      that the modification guaranteed adequate circulation across the antimesenteric
      border and from the proximal to the distal end of the flap. CONCLUSION: In
      conclusion, an incision along 1 side of the mesenteric border produces increased
      mobility of the jejunal seromuscular patch flap. Angiography can demonstrate
      clear evidence of a reliable circulation.

PMID- 24569135
TI  - Vitellogenesis of the digenean Plagiorchis elegans (Rudolphi, 1802)
      (Plagiorchioidea, Plagiorchiidae).
AB  - The ultrastructural organization of vitellogenesis of Plagiorchis elegans
      (Rudolphi, 1802), experimentally obtained from the golden hamster Mesocricetus
      auratus (Linnaeus, 1758), is described using transmission electron microscopy.
      This study is the first ultrastructural study of vitellogenesis in a member of
      the superfamily Plagiorchioidea. The four stages usually observed during
      vitellogenesis are described: stage I, cytoplasm of the vitellocytes mainly
      filled with ribosomes and few mitochondria; stage II, beginning of the synthetic
      activity; stage III, active synthesis of the shell globule clusters; stage IV,
      vitellocytes are filled with shell globule clusters and contain several lipid
      droplets, and glycogen granules are grouped around clusters and droplets.
      Vitellogenesis in P. elegans is compared with that of other Digenea. The
      differences among P. elegans and previously studied digeneans include, but are
      not limited to the occurrence of dense coiled endoplasmic reticulum saccules and
      the concentration of glycogen in the mesenchyme, which may be considered as a
      fifth stage of maturation of the vitelline glands. This peculiarity was not
      observed in all trematodes, which clearly indicates differences in the
      vitellogenesis in various digenean lineages at different stages of maturation of
      their vitelline cells. 

PMID- 24569136
TI  - [Digestive diseases in the epistolary collection of 16th century].
AB  - Correspondence is an important source of documentation for studying health and,
      therefore, the gastrointestinal symptoms of diseases. We studied the
      gastrointestinal disease described in the Monumenta Borgia collection, which
      contains documents from the 16th century, mainly letters about Francis Borgia,
      the last great figure of a family originally from Valencia and with universal
      significance. Of the 2769 documents examined, 1231 (44.5%) contained some health
      related descriptions and 42 items were related to gastrointestinal disease,
      representing 7.5% of the specific diseases of natural causes. The most frequently
      mentioned organ in the whole human body was the stomach, with 20 references. The
      most frequent references were to symptoms related to the upper gastrointestinal
      tract, with 18 references, and the lower gastrointestinal tract, with 16. The
      comments made on health related to gastrointestinal disease usually reflect the
      typical galenism of the medicine of the times. The disorders attributed to the
      stomach are described in varied terminology and include an acute episode of
      gastrointestinal bleeding. The most frequently mentioned symptoms and processes
      are diarrhea, flatulence, hernias, and, among those attributed to the lower
      gastrointestinal tract, lower gastrointestinal hemorrhages. Also mentioned are
      hemorrhoids and intestinal colic. Although little mention is made of the liver
      and spleen, there are various allusions that Francis Borgia was affected by
      disease or pathogenic alterations in this area. However, the postmortem
      examination of his corpse, refuted the existence of these anomalies. 

PMID- 24569137
TI  - [Patient with HBsAg negativization during treatment. Could it be considered a
      cure for hepatitis B?].

PMID- 24569138
TI  - [Mycoplasma-associated acute hepatitis in an adult patient without pulmonary
      involvement].

PMID- 24569139
TI  - Selective evaluation of high density lipoprotein from mouse small intestine by an
      in situ perfusion technique.
AB  - The small intestine (SI) is the second-greatest source of HDL in mice. However,
      the selective evaluation of SI-derived HDL (SI-HDL) has been difficult because
      even the origin of HDL obtained in vivo from the intestinal lymph duct of
      anesthetized rodents is doubtful. To shed light on this question, we have
      developed a novel in situ perfusion technique using surgically isolated mouse SI,
      with which the possible filtration of plasma HDL into the SI lymph duct can be
      prevented. With the developed method, we studied the characteristics of and
      mechanism for the production and regulation of SI-HDL. Nascent HDL particles were
      detected in SI lymph perfusates in WT mice, but not in ABCA1 KO mice. SI-HDL had
      a high protein content and was smaller than plasma HDL. SI-HDL was rich in TG and
      apo AIV compared with HDL in liver perfusates. SI-HDL was increased by high-fat
      diets and reduced in apo E KO mice. In conclusion, with our in situ perfusion
      model that enables the selective evaluation of SI-HDL, we demonstrated that ABCA1
      plays an important role in intestinal HDL production, and SI-HDL is small, dense,
      rich in apo AIV, and regulated by nutritional and genetic factors.

PMID- 24569141
TI  - Localized scleroderma and regional inflammatory myopathy.
AB  - Inflammatory myopathy is rare in localized scleroderma. We report 2 new cases of
      regional inflammatory myopathy associated with localized scleroderma and review
      10 reported cases of localized scleroderma associated with an inflammatory
      myopathy with regional muscle involvement, more often in the upper extremities.
      Serum creatine kinase was mildly elevated or normal. Histopathology often showed
      perimysial inflammation and plasma cell infiltration. These cases demonstrate
      that inflammatory myopathy should be considered in patients with localized
      scleroderma and regional muscle weakness, pain or atrophy. Muscle biopsy can
      confirm the diagnosis of myositis, which if identified, will require anti
      inflammatory and/or immunosuppressive therapy. 

PMID- 24569140
TI  - Endoplasmic reticulum microenvironment and conserved histidines govern ELOVL4
      fatty acid elongase activity.
AB  - Autosomal dominant Stargardt-like macular dystrophy (STGD3) in humans results
      from mutations in elongation of very long chain FAs-like 4 (ELOVL4), which leads
      to vision loss in young adults. ELOVL4 is an integral endoplasmic reticulum (ER)
      protein that mediates the elongation of very long chain (VLC) FAs. Mutations in
      ELOVL4 lead to truncation and mislocalization of the translated protein from the
      ER, the site of FA elongation. Little is known about the enzymatic elongation of
      VLC-FAs by ELOVL4. We over-expressed full-length mouse ELOVL4, an N-glycosylation
      deficient mutant, an ER-retention mutant, and mutants of active site histidines
      to parse their individual roles in VLC-FA elongation. ELOVL4 elongated
      appropriate precursors to the corresponding VLC-FA species >= 28 carbons. Active
      site histidine mutants of ELOVL4 did not elongate appropriate precursors,
      establishing ELOVL4 as the elongase. Displacing ELOVL4 from the ER was sufficient
      to cause loss of condensation activity, while absence of N-glycosylation was
      irrelevant for enzyme function. This study shows that ELOVL4 enzymatic activity
      is governed by individual histidines in its active site and the ER
      microenvironment, both of which are essential for elongation of VLC-FAs.

PMID- 24569143
TI  - The 3rd International Patellofemoral Research Retreat: an international expert
      consensus meeting to improve the scientific understanding and clinical management
      of patellofemoral pain.

PMID- 24569144
TI  - Is patellofemoral osteoarthritis a common sequela of patellofemoral pain?

PMID- 24569142
TI  - Dendritic cells: In vitro culture in two- and three-dimensional collagen systems
      and expression of collagen receptors in tumors and atherosclerotic
      microenvironments.
AB  - Dendritic cells (DCs) are immune cells found in the peripheral tissues where they
      sample the organism for infections or malignancies. There they take up antigens
      and migrate towards immunological organs to contact and activate T lymphocytes
      that specifically recognize the antigen presented by these antigen presenting
      cells. In the steady state there are several types of resident DCs present in
      various different organs. For example, in the mouse, splenic DC populations
      characterized by the co-expression of CD11c and CD8 surface markers are
      specialized in cross-presentation to CD8 T cells, while CD11c/SIRP-1alpha DCs
      seem to be dedicated to activating CD4 T cells. On the other hand, DCs have also
      been associated with the development of various diseases such as cancer,
      atherosclerosis, or inflammatory conditions. In such disease, DCs can participate
      by inducing angiogenesis or immunosuppression (tumors), promoting autoimmune
      responses, or exacerbating inflammation (atherosclerosis). This change in DC
      biology can be prompted by signals in the microenvironment. We have previously
      shown that the interaction of DCs with various extracellular matrix components
      modifies the immune properties and angiogenic potential of these cells. Building
      on those studies, herewith we analyzed the angiogenic profile of murine myeloid
      DCs upon interaction with 2D and 3D type-I collagen environments. As determined
      by PCR array technology and quantitative PCR analysis we observed that
      interaction with these collagen environments induced the expression of particular
      angiogenic molecules. In addition, DCs cultured on collagen environments
      specifically upregulated the expression of CXCL-1 and -2 chemokines. We were also
      able to establish DC cultures on type-IV collagen environments, a collagen type
      expressed in pathological conditions such as atherosclerosis. When we examined DC
      populations in atherosclerotic veins of Apolipoprotein E deficient mice we
      observed that they expressed adhesion molecules capable of interacting with
      collagen. Finally, to further investigate the interaction of DCs with collagen in
      other pathological conditions, we determined that both murine ovarian and breast
      cancer cells express several collagen molecules that can contribute to shape
      their particular tumor microenvironment. Consistently, tumor-associated DCs were
      shown to express adhesion molecules capable of interacting with collagen
      molecules as determined by flow cytometry analysis. Of particular relevance,
      tumor-associated DCs expressed high levels of CD305/LAIR-1, an immunosuppressive
      receptor. This suggests that signaling through this molecule upon interaction
      with collagen produced by tumor cells might help define the poorly immunogenic
      status of these cells in the tumor microenvironment. Overall, these studies
      demonstrate that through interaction with collagen proteins, DCs can be capable
      of modifying the microenvironments of inflammatory disease such as cancer or
      atherosclerosis. 

PMID- 24569145
TI  - Patellofemoral pain: consensus statement from the 3rd International
      Patellofemoral Pain Research Retreat held in Vancouver, September 2013.

PMID- 24569147
TI  - Nerve resection for the treatment of chronic neuropathic pain.

PMID- 24569146
TI  - Sensitization of cutaneous neuronal purinergic receptors contributes to
      endothelin-1-induced mechanical hypersensitivity.
AB  - Endothelin (ET-1), an endogenous peptide with a prominent role in cutaneous pain,
      causes mechanical hypersensitivity in the rat hind paw, partly through mechanisms
      involving local release of algogenic molecules in the skin. The present study
      investigated involvement of cutaneous ATP, which contributes to pain in numerous
      animal models. Pre-exposure of ND7/104 immortalized sensory neurons to ET-1
      (30nM) for 10min increased the proportion of cells responding to ATP (2MUM) with
      an increase in intracellular calcium, an effect prevented by the ETA receptor
      selective antagonist BQ-123. ET-1 (3nM) pre-exposure also increased the
      proportion of isolated mouse dorsal root ganglion neurons responding to ATP (0.2
      0.4MUM). Blocking ET-1-evoked increases in intracellular calcium with the IP3
      receptor antagonist 2-APB did not inhibit sensitization to ATP, indicating a
      mechanism independent of ET-1-mediated intracellular calcium increases. ET-1
      sensitized ATP calcium responses were largely abolished in the absence of
      extracellular calcium, implicating ionotropic P2X receptors. Experiments using
      quantitative polymerase chain reaction and receptor-selective ligands in ND7/104
      showed that ET-1-induced sensitization most likely involves the P2X4 receptor
      subtype. ET-1-sensitized calcium responses to ATP were strongly inhibited by
      broad-spectrum (TNP-ATP) and P2X4-selective (5-BDBD) antagonists, but not
      antagonists for other P2X subtypes. TNP-ATP and 5-BDBD also significantly
      inhibited ET-1-induced mechanical sensitization in the rat hind paw, supporting a
      role for purinergic receptor sensitization in vivo. These data provide evidence
      that mechanical hypersensitivity caused by cutaneous ET-1 involves an increase in
      the neuronal sensitivity to ATP in the skin, possibly due to sensitization of
      P2X4 receptors. 

PMID- 24569148
TI  - Decoding the matrix: benefits and limitations of applying machine learning
      algorithms to pain neuroimaging.

PMID- 24569149
TI  - A brief cognitive-behavioural intervention for pain reduces secondary
      hyperalgesia.
AB  - Repeated exposure to pain can result in sensitization of the central nervous
      system, enhancing subsequent pain and potentially leading to chronicity. The
      ability to reverse this sensitization in a top-down manner would be of tremendous
      clinical benefit, but the degree that this can be accomplished volitionally
      remains unknown. Here we investigated whether a brief (~5 min) cognitive
      behavioural intervention could modify pain perception and reduce central
      sensitization (as reflected by secondary hyperalgesia). In each of 8 sessions, 2
      groups of healthy human subjects received a series of painful thermal stimuli
      that resulted in secondary hyperalgesia. One group (regulate) was given brief
      pain-focused cognitive training at each session, while the other group (control)
      received a non-pain-focused intervention. The intervention selectively reduced
      pain unpleasantness but not pain intensity in the regulate group. Furthermore,
      secondary hyperalgesia was significantly reduced in the regulate group compared
      with the control group. Reduction in secondary hyperalgesia was associated with
      reduced pain catastrophizing, suggesting that changes in central sensitization
      are related to changes in pain-related cognitions. Thus, we demonstrate that
      central sensitization can be modified volitionally by altering pain-related
      thoughts.

PMID- 24569150
TI  - Microbial exposure and onset of allergic diseases - potential prevention
      strategies?
AB  - Chronic inflammatory diseases are a major health problem with global dimension.
      Particularly, the incidence of allergic diseases has been increased tremendously
      within the last decades. This world-wide trend clearly indicates the demand for
      new approaches in the investigation of early allergy development. Recent studies
      underlined the basic postulate of the hygiene hypothesis that early exposure to
      microbial stimuli plays a crucial role in the prevention of chronic inflammatory
      conditions in adulthood. There is ample evidence that, both, exogenous microbes
      and endogenous microbial communities, the human microbiota, shape the developing
      immune system and might be involved in prevention of pathologic pro-inflammatory
      trails. According to the Barker hypothesis, epidemiological studies pointed to
      transmaternal transmission from the mother to the offspring already in prenatal
      life. Experimental data from murine models support these findings. This state of
      the art review provides an overview on the current literature and presents new
      experimental concepts that point out to future application in the prevention of
      allergic diseases. 

PMID- 24569151
TI  - Oral mite anaphylaxis caused by mite-contaminated okonomiyaki/ pancake-mix in
      Japan: 8 case reports and a review of 28 reported cases.
AB  - BACKGROUND: Anaphylaxis after the ingestion of foods contaminated with mites has
      recently been recognized. Case series and case reports thus far have shown that
      mite-contaminated wheat flour is the major cause of oral mite anaphylaxis.
      However, we have found 8 cases of oral mite anaphylaxis which were caused by mite
      contaminated okonomiyaki-mix, a savory Japanese style pancake mix, in our
      hospital. METHODS: In addition to our 8 cases, the databases of MEDLINE and
      ICHUSHI were systematically searched for patients with oral mite anaphylaxis in
      Japan. RESULTS: Thirty-six patients including our 8 cases with oral mite
      anaphylaxis were identified. Thirty-four out of 36 cases (94%) ingested
      okonomiyaki or takoyaki, prepared at home using okonomiyaki-mix or takoyaki-mix
      which was previously opened and stored for months at ambient temperature.
      Microscopic examination of culprit mixes of 16 cases including our 1 case
      revealed contamination of mites such as Dermatophagoides farina (Der f) (5
      cases), Tyrophagus putrescentiae (Tyr p) (4 cases), and Dermatophagoides
      pteronyssinus (Der p) (3 cases). The specific IgE to each mite is generally
      upregulated in these patients. Especially, the titers of specific IgE to Der p
      and Der f were more than class 2 in all cases. CONCLUSIONS: Mite-contaminated
      flavored flour is the major cause of oral mite anaphylaxis in Japan.

PMID- 24569152
TI  - Continuous 6-year follow-up study of sensitization to Japanese cedar pollen and
      onset in schoolchildren.
AB  - BACKGROUND: Intra individual longitudinal data has been lacking for IgE-mediated
      seasonal allergic rhinitis (SAR), especially in young children. Little is known
      about the development and natural course of SAR in terms of prevalence and
      incidence rates in schoolchildren. METHODS: In May or June each year from 1994 to
      2007, schoolchildren were assessed for serum Japanese cedar pollen (JCP)-IgE and
      house dust mite (HDM)-IgE levels, and surveyed regarding nasal symptoms. RESULTS:
      Among the 220 children initially assessed in the first grade, 69 (31.4%) were
      already sensitized to JCP at first grade and 119 (54.1%) did not develop JCP
      sensitivity during the 6-year study at all. In the first grade children who were
      HDM-sensitized but JCP non-sensitized, JCP-IgE level was significantly elevated
      compared to the JCP and HDM non-sensitized group. This seems to indicate that HDM
      sensitization was very strongly associated with JCP sensitization. CONCLUSIONS:
      Elevated serum IgE is a consequence of specific sensitization to HDM and HDM
      sensitization appeared to develop prior to the start of primary school which
      distinguishes HDM sensitization from JCP sensitization.

PMID- 24569153
TI  - A comparison of long-term anti-inflammatory effect of two ICS/LABA combination
      inhalers; fix-dosed maintenance therapy with budesonide/formoterol and
      salmeterol/fluticasone.
AB  - BACKGROUND: The clinical usefulness of fixed-dose maintenance therapy with
      salmeterol/fluticasone (SFC) and budesonide/formoterol combination inhaler
      (BUD/FM) has been established, though evidence of the long-term anti-inflammatory
      effects of these 2 inhalers are limited. METHODS: Patients with moderate
      persistent adult asthma who had received SFC 50/250MUg bid with well-control
      status were recruited. After switching to 8-week therapy with fixed-dose BUD/FM 4
      puffs (640/18MUg) (phase-1), patients chose either SFC or BUD/FM. FeNO and ACT
      score were evaluated every 8 weeks until the end of the 52-week treatment period
      for both treatment groups (phase-2). RESULTS: In total, 103 patients were
      examined: BUD/FM was chosen by 34 patients (BUD/FM group), while SFC was chosen
      by 23 (SFC group). Thirty-six received SFC consistently from the beginning of the
      study (control). Patients in the BUD/FM and SFC groups showed significant
      improvements in ACT scores and FeNO levels in phase-1; these beneficial effects
      persisted for 52 weeks in the BUD/FM group. On the other hand, in the SFC group,
      although the FeNO level decreased from 54.3 +/- 26.4 ppb to 41.9 +/- 18.3 ppb in
      phase-1, it increased to 54.5 +/- 26.2 ppb, a level similar to the baseline prior
      to the beginning of BUD/FM therapy, at 8 weeks in phase-2, and remained at 50-odd
      ppb thereafter. CONCLUSIONS: These results suggest that maintenance therapy with
      fixed-dose BUD/FM is a useful treatment option exerting an airway anti
      inflammatory effect for a period as long as 1 year, even for asthmatics who could
      not accomplish total control with SFC.

PMID- 24569154
TI  - Reference values for Japanese children's respiratory resistance using the LMS
      method.
AB  - BACKGROUND: The forced oscillation technique (FOT) is useful for studying
      pulmonary function in children, as well as in school children with asthma.
      However, the standard values for respiratory resistance (Rrs) in Asian school
      children remain unknown. We evaluated the standard Rrs using a type of FOT,
      impulse oscillometry (IOS), in healthy Japanese children at elementary and junior
      high schools. METHODS: A total of 795 children (age range: 6-15 years; mean age
      +/- SD: 11.1 +/- 2.4 years; 404 boys, 391 girls) at elementary and junior high
      schools participated in the study. Of the 795 children, we evaluated the Rrs of
      537 children aged 6-15 years (mean +/- SD: 10.8 +/- 2.4 years) using IOS.
      RESULTS: Regression analyses with three IOS parameters, Rrs at 5Hz (R5), Rrs at
      20Hz (R20), and Rrs difference between 5Hz and 20Hz (R5-R20), for age, height,
      weight, and degree of obesity as independent variables demonstrated the strongest
      correlation between each parameter and children's height. All parameters
      decreased with increasing height. Using the lambda-mu-sigma (LMS) method, we
      created standard curves for the Rrs values based on height. CONCLUSIONS: Our
      standard curves could be useful for diagnosis and control evaluation of childhood
      asthma.

PMID- 24569157
TI  - The empowerment of low-income parents engaged in a childhood obesity
      intervention.
AB  - Parents influence children's obesity risk factors but are infrequently targeted
      for interventions. This study targeting low-income parents integrated a community
      based participatory research approach with the Family Ecological Model and
      Empowerment Theory to develop a childhood obesity intervention. This article (1)
      examines pre- to postintervention changes in parents' empowerment; (2) determines
      the effects of intervention dose on empowerment, and (3) determines whether
      changes in parent empowerment mediate previous changes identified in food-,
      physical activity-, and screen-related parenting. The pre-post quasi-experimental
      design evaluation demonstrated positive changes in parent empowerment and
      empowerment predicted improvement in parenting practices. The integrated model
      applied in this study provides a means to enhance intervention relevance and
      guide translation to other childhood obesity and health disparities studies. 

PMID- 24569159
TI  - Self-management program participation by older adults with diabetes: Chronic
      Disease Self-Management Program and Diabetes Self-Management Program.
AB  - The Chronic Disease Self-Management Program and the Diabetes Self-Management
      Program offer evidence-based self-management for persons with diabetes. We
      examined participation and completion rates for older adults in the Communities
      Putting Prevention to Work initiative and found that completion is more likely
      (1) in Diabetes Self-Management Program for individuals with diabetes; (2) for
      Chronic Disease Self-Management Program and Diabetes Self-Management Program with
      introductory class zero; and (3) in small classes. We also found that
      participants reporting depression were less likely to complete either workshop.
      Future research is needed to examine workshop availability and selection, health
      and behavioral outcomes, and participant/completer experience. 

PMID- 24569160
TI  - Translating using RE-AIM of a falls behavior change program among an assisted
      living population.
AB  - A Matter of Balance/Volunteer Lay Leader model is an evidence-based program to
      change behavior to adopt falls prevention strategies. The purpose was to
      translate this program to assisted living communities. A single-arm intervention
      study was designed to assess for falls-related and physical performance measures.
      Forty-one residents, with a mean age of 87 years, were eligible for
      participation. The Falls Management Scale (P = .02) and the Physical Component
      Summary Score (P = .01) significantly improved from baseline to 8 weeks. Gait
      speed (P = .059) was borderline significant from baseline to 6 months. We showed
      evidence for successful translation within the assisted living communities
      sampled. 

PMID- 24569161
TI  - Translation of function-focused care to assisted living facilities.
AB  - Assisted livings settings are residential settings that provide housing and
      supportive services for older and disabled adults. Although individuals in
      assisted living settings are less functionally impaired than those in nursing
      home settings, they engage in limited amounts of physical activity and decline
      functionally more rapidly than their peers in nursing homes. Function-focused
      care for assisted living (FFC-AL) was developed to prevent decline, improve
      function, and increase physical activity among residents living in these
      settings. The purpose of this study was to translate the previously established,
      effective FFC-AL intervention to 20 assisted living facilities. Evidence of our
      ability to successfully translate function-focused care into these 20 assisted
      living facilities was determined using the RE-AIM (Reach, Efficacy/Effectiveness,
      Adoption, Implementation, and Maintenance) model. Our findings supported our
      ability to translate FFC-AL effectively into 18 of these 20 settings, using our
      dissemination and implementation approach. 

PMID- 24569158
TI  - Adapting hypertension self-management interventions to enhance their sustained
      effectiveness among urban African Americans.
AB  - African Americans suffer disproportionately poor hypertension control despite the
      availability of efficacious interventions. Using principles of community-based
      participatory research and implementation science, we adapted established
      hypertension self-management interventions to enhance interventions' cultural
      relevance and potential for sustained effectiveness among urban African
      Americans. We obtained input from patients and their family members, their health
      care providers, and community members. The process required substantial time and
      resources, and the adapted interventions will be tested in a randomized
      controlled trial. 

PMID- 24569162
TI  - Genetic instability in lymphoblastoid cell lines expressing biallelic and
      monoallelic variants in the human MUTYH gene.
AB  - The MUTYH DNA glycosylase counteracts mutagenesis by removing adenine
      misincorporated opposite DNA 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG).
      Biallelic germline mutations in MUTYH cause the autosomal recessive MUTYH
      associated polyposis (MAP). The impact on genetic instability of the p.Tyr179Cys
      and p.Arg245His MUTYH variants was evaluated in lymphoblastoid cell lines (LCLs)
      derived from MAP patients and their relatives in comparison to wild-type LCLs. No
      difference in MUTYH expression was identified between wild type and LCLs with the
      p.Tyr179Cys, while the p.Arg245His mutation was associated with an unstable MUTYH
      protein. LCLs homozygous for the p.Tyr179Cys or the p.Arg245His variant contained
      increased DNA 8-oxodG levels and exhibited a mutator phenotype at the PIG-A gene.
      The extent of the increased spontaneous mutation frequency was 3-fold (range 1.6-
      to 4.6-fold) in four independent LCLs carrying the p.Tyr179Cys variant, while a
      larger increase (6-fold) was observed in two p.Arg245His LCLs. A similar
      hypermutability and S-phase delay following treatment with KBrO3 was observed in
      LCLs homozygous for either variant. When genetic instability was investigated in
      monoallelic p.Arg245His carriers, mutant frequencies showed an increase which is
      intermediate between wild-type and homozygous cells, whereas the mutator effect
      in heterozygous p.Tyr179Cys LCLs was similar to that in homozygotes. These
      findings indicate that the type of MUTYH mutation can affect the extent of genome
      instability associated with MUTYH inactivation. In addition, the mild spontaneous
      mutator phenotype observed in monoallelic carriers highlights the biological
      importance of this gene in the protection of the genome against endogenous DNA
      damage. 

PMID- 24569163
TI  - Statistical insights into major human muscular diseases.
AB  - Muscular diseases lead to muscle fiber degeneration, impairment of mobility, and
      in some cases premature death. Many of these muscular diseases are largely
      idiopathic. The goal of this study was to identify biomarkers based on their
      functional role and possible mechanisms of pathogenesis, specific to individual
      muscular disease. We analyzed the muscle transcriptome from five major muscular
      diseases: acute quadriplegic myopathy (AQM), amyotrophic lateral sclerosis (ALS),
      mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes
      (MELAS), dermatomyositis (DM) and polymyositis (PM) using pairwise statistical
      comparison to identify uniquely regulated genes in each muscular disease. The
      genome-wide information encoded in the transcriptome provided biomarkers and
      functional insights into dysregulation in each muscular disease. The analysis
      showed that the dysregulation of genes in forward membrane pathway, responsible
      for transmitting action potential from neural excitation, is unique to AQM, while
      the dysregulation of myofibril genes, determinant of the mechanical properties of
      muscle, is unique to ALS, dysregulation of ER protein processing, responsible for
      correct protein folding, is unique to DM, and upregulation of immune response
      genes is unique to PM. We have identified biomarkers specific to each muscular
      disease which can be used for diagnostic purposes. 

PMID- 24569164
TI  - Comprehensive annotation of splice junctions supports pervasive alternative
      splicing at the BRCA1 locus: a report from the ENIGMA consortium.
AB  - Loss-of-function germline mutations in BRCA1 (MIM #113705) confer markedly
      increased risk of breast and ovarian cancer. The full-length transcript codifies
      for a protein involved in DNA repair pathways and cell-cycle checkpoints. Several
      BRCA1 splicing isoforms have been described in public domain databases, but the
      physiological role (if any) of BRCA1 alternative splicing remains to be
      established. An accurate description of 'naturally occurring' alternative
      splicing at this locus is a prerequisite to understand its biological
      significance. However, a systematic analysis of alternative splicing at the BRCA1
      locus is yet to be conducted. Here, the Evidence-Based Network for the
      Interpretation of Germ-Line Mutant Alleles consortium combines RT-PCR, exon
      scanning, cloning, sequencing and relative semi-quantification to describe
      naturally occurring BRCA1 alternative splicing with unprecedented resolution. The
      study has been conducted in blood-related RNA sources, commonly used for clinical
      splicing assays, as well as in one healthy breast tissue. We have characterized a
      total of 63 BRCA1 alternative splicing events, including 35 novel findings. A
      minimum of 10 splicing events (Delta1Aq, Delta5, Delta5q, Delta8p, Delta9,
      Delta(9,10), Delta9_11, Delta11q, Delta13p and Delta14p) represent a substantial
      fraction of the full-length expression level (ranging from 5 to 100%).
      Remarkably, our data indicate that BRCA1 alternative splicing is similar in blood
      and breast, a finding supporting the clinical relevance of blood-based in vitro
      splicing assays. Overall, our data suggest an alternative splicing model in which
      most non-mutually exclusive alternative splicing events are randomly combined
      into individual mRNA molecules to produce hundreds of different BRCA1 isoforms. 

PMID- 24569165
TI  - The ALS gene FUS regulates synaptic transmission at the Drosophila neuromuscular
      junction.
AB  - Mutations in the RNA binding protein Fused in sarcoma (FUS) are estimated to
      account for 5-10% of all inherited cases of amyotrophic lateral sclerosis (ALS),
      but the function of FUS in motor neurons is poorly understood. Here, we
      investigate the early functional consequences of overexpressing wild-type or ALS
      associated mutant FUS proteins in Drosophila motor neurons, and compare them to
      phenotypes arising from loss of the Drosophila homolog of FUS, Cabeza (Caz). We
      find that lethality and locomotor phenotypes correlate with levels of FUS
      transgene expression, indicating that toxicity in developing motor neurons is
      largely independent of ALS-linked mutations. At the neuromuscular junction (NMJ),
      overexpression of either wild-type or mutant FUS results in decreased number of
      presynaptic active zones and altered postsynaptic glutamate receptor subunit
      composition, coinciding with a reduction in synaptic transmission as a result of
      both reduced quantal size and quantal content. Interestingly, expression of human
      FUS downregulates endogenous Caz levels, demonstrating that FUS autoregulation
      occurs in motor neurons in vivo. However, loss of Caz from motor neurons
      increases synaptic transmission as a result of increased quantal size, suggesting
      that the loss of Caz in animals expressing FUS does not contribute to motor
      deficits. These data demonstrate that FUS/Caz regulates NMJ development and plays
      an evolutionarily conserved role in modulating the strength of synaptic
      transmission in motor neurons. 

PMID- 24569167
TI  - Respiratory failure, cleft palate and epilepsy in the mouse model of human Xq22.1
      deletion syndrome.
AB  - Chromosomal segmental deletion is a frequent cause of human diseases. A familial
      1.1 Mb deletion of human chromosome Xq22.1 associates with epilepsy, cleft palate
      and developmental defects in heterozygous female patients. Here, we describe a
      mouse mutant with a targeted deletion of the syntenic segment of the mouse X
      chromosome that phenocopies the human syndrome. Male mice with a deletion of a
      1.1 Mb Nxf2-Nxf3 X-chromosomal segment exhibit respiratory failure, neonatal
      lethality and cleft palate. In female mice, heterozygosity for the deletion
      manifests cleft palate, early postnatal lethality, postnatal growth delay and
      spontaneous seizures in surviving animals, apparently due to X-chromosome
      inactivation. Furthermore, loss of a 0.35 Mb subregion containing Armcx5,
      Gprasp1, Gprasp2 and Bhlhb9 is sufficient to cause the Xq22.1 syndrome phenotype.
      Our results support that the 1.1 Mb deletion of human Xq22.1 is the genetic cause
      of the associated syndrome. 

PMID- 24569166
TI  - DLX5, FGF8 and the Pin1 isomerase control DeltaNp63alpha protein stability during
      limb development: a regulatory loop at the basis of the SHFM and EEC congenital
      malformations.
AB  - Ectrodactyly, or Split-Hand/Foot Malformation (SHFM), is a congenital condition
      characterized by the loss of central rays of hands and feet. The p63 and the
      DLX5;DLX6 transcription factors, expressed in the embryonic limb buds and
      ectoderm, are disease genes for these conditions. Mutations of p63 also cause the
      ectodermal dysplasia-ectrodactyly-cleft lip/palate (EEC) syndrome, comprising
      SHFM. Ectrodactyly is linked to defects of the apical ectodermal ridge (AER) of
      the developing limb buds. FGF8 is the key signaling molecule in this process,
      able to direct proximo-distal growth and patterning of the skeletal primordial of
      the limbs. In the limb buds of both p63 and Dlx5;Dlx6 murine models of SHFM, the
      AER is poorly stratified and FGF8 expression is severely reduced. We show here
      that the FGF8 locus is a downstream target of DLX5 and that FGF8 counteracts Pin1
      DeltaNp63alpha interaction. In vivo, lack of Pin1 leads to accumulation of the
      p63 protein in the embryonic limbs and ectoderm. We show also that DeltaNp63alpha
      protein stability is negatively regulated by the interaction with the prolyl
      isomerase Pin1, via proteasome-mediated degradation; p63 mutant proteins
      associated with SHFM or EEC syndromes are resistant to Pin1 action. Thus, DLX5,
      p63, Pin1 and FGF8 participate to the same time- and location-restricted
      regulatory loop essential for AER stratification, hence for normal patterning and
      skeletal morphogenesis of the limb buds. These results shed new light on the
      molecular mechanisms at the basis of the SHFM and EEC limb malformations. 

PMID- 24569168
TI  - Alternative polyadenylation diversifies post-transcriptional regulation by
      selective RNA-protein interactions.
AB  - Recent research has uncovered extensive variability in the boundaries of
      transcript isoforms, yet the functional consequences of this variation remain
      largely unexplored. Here, we systematically discriminate between the molecular
      phenotypes of overlapping coding and non-coding transcriptional events from each
      genic locus using a novel genome-wide, nucleotide-resolution technique to
      quantify the half-lives of 3' transcript isoforms in yeast. Our results reveal
      widespread differences in stability among isoforms for hundreds of genes in a
      single condition, and that variation of even a single nucleotide in the 3'
      untranslated region (UTR) can affect transcript stability. While previous
      instances of negative associations between 3' UTR length and transcript stability
      have been reported, here, we find that shorter isoforms are not necessarily more
      stable. We demonstrate the role of RNA-protein interactions in conditioning
      isoform-specific stability, showing that PUF3 binds and destabilizes specific
      polyadenylation isoforms. Our findings indicate that although the functional
      elements of a gene are encoded in DNA sequence, the selective incorporation of
      these elements into RNA through transcript boundary variation allows a single
      gene to have diverse functional consequences. 

PMID- 24569169
TI  - Single molecule approaches to monitor the recognition and resection of double
      stranded DNA breaks during homologous recombination.
AB  - The fate of a cell depends on its ability to repair the many double-stranded DNA
      breaks (DSBs) that occur during normal metabolism. Improper DSB repair may result
      in genomic instability, cancer, or other genetic diseases. The repair of a DSB
      can be initiated by the recognition and resection of a duplex DNA end to form a
      3'-terminated single-stranded DNA overhang. This task is carried out by different
      single-strand exonucleases, endonucleases, and helicases that work in a
      coordinated manner. This manuscript reviews the different single-molecule
      approaches that have been employed to characterize the structural features of
      these molecular machines, as well as the intermediates and products formed during
      the process of DSB repair. Imaging techniques have unveiled the structural
      organization of complexes involved in the tethering and recognition of DSBs. In
      addition to that static picture, single molecule studies on the dynamics of
      helicase-nuclease complexes responsible for the processive resection of DSBs have
      provided detailed mechanistic insights into their function. 

PMID- 24569171
TI  - Atypical teratoid rhabdoid tumor in adulthood.

PMID- 24569172
TI  - Evidence for classic complement activity in neuromyelitis optica.

PMID- 24569173
TI  - Ganglioglioma of the conus medullaris associated with vertebral body hemangioma.

PMID- 24569174
TI  - Pediatric supratentorial cortical tanycytic ependymoma associated with absence
      seizures.

PMID- 24569170
TI  - Unraveling secrets of telomeres: one molecule at a time.
AB  - Telomeres play important roles in maintaining the stability of linear
      chromosomes. Telomere maintenance involves dynamic actions of multiple proteins
      interacting with long repetitive sequences and complex dynamic DNA structures,
      such as G-quadruplexes, T-loops and t-circles. Given the heterogeneity and
      complexity of telomeres, single-molecule approaches are essential to fully
      understand the structure-function relationships that govern telomere maintenance.
      In this review, we present a brief overview of the principles of single-molecule
      imaging and manipulation techniques. We then highlight results obtained from
      applying these single-molecule techniques for studying structure, dynamics and
      functions of G-quadruplexes, telomerase, and shelterin proteins. 

PMID- 24569175
TI  - Characterization of two genes for the biosynthesis of abietane-type diterpenes in
      rosemary (Rosmarinus officinalis) glandular trichomes.
AB  - Rosemary (Rosmarinus officinalis) produces the phenolic diterpenes carnosic acid
      and carnosol, which, in addition to their general antioxidant activities, have
      recently been suggested as potential ingredients for the prevention and treatment
      of neurodegenerative diseases. Little is known about the biosynthesis of these
      diterpenes. Here we show that the biosynthesis of phenolic diterpenes in rosemary
      predominantly takes place in the glandular trichomes of young leaves, and used
      this feature to identify the first committed steps. Thus, a copalyl diphosphate
      synthase (RoCPS1) and two kaurene synthase-like (RoKSL1 and RoKSL2) encoding
      genes were identified and characterized. Expression in yeast (Saccharomyces
      cerevisiae) and Nicotiana benthamiana demonstrate that RoCPS1 converts
      geranylgeranyl diphosphate (GGDP) to copalyl diphosphate (CDP) of normal
      stereochemistry and that both RoKSL1 and RoKSL2 use normal CDP to produce an
      abietane diterpene. Comparison to the already characterized diterpene synthase
      from Salvia miltiorrhiza (SmKSL) demonstrates that the product of RoKSL1 and
      RoKSL2 is miltiradiene. Expression analysis supports a major contributing role
      for RoKSL2. Like SmKSL and the sclareol synthase from Salvia sclarea, RoKSL1/2
      are diterpene synthases of the TPS-e group which have lost the internal gamma
      domain. Furthermore, phylogenetic analysis indicates that RoKSL1 and RoKSL2
      belong to a distinct group of KSL enzymes involved in specialized metabolism
      which most likely emerged before the dicot-monocot split. 

PMID- 24569176
TI  - The haploinsufficiency profile of alpha-hederin suggests a caspofungin-like
      antifungal mode of action.
AB  - The leaves of common ivy (Hedera helix) contain the cytotoxic saponin alpha
      hederin, which is inhibitory to Candida albicans at low concentrations. To
      investigate the mode of action of alpha-hederin, a haploinsufficiency screen was
      carried out using a library of 1152 Saccharomyces cerevisiae deletion strains. An
      ethanol ivy extract containing alpha-hederin was used in the initial screen to
      reduce the amount of compound required. Strains exhibiting disproportionately low
      growth were then examined in more detail by comparing growth curves in the
      presence and absence of alpha-hederin. This approach identified three
      hypersensitive strains carrying gene deletions for components of the
      transcription related proteins SWI/SNF, RNA polymerase II and the RSC complex.
      Saponin cytotoxicity is often attributed to membrane damage, however alpha
      hederin did not induce hypersensitivity with an aminophospholipid translocase
      deletion strain that is frequently hypersensitive to membrane damaging agents.
      The haploinsufficiency profile of alpha-hederin is most similar to that reported
      for drugs such as caspofungin that inhibit synthesis of the fungal cell wall.
      Screening with plant extracts rather than isolated compounds, provides a valuable
      shortcut in haploinsufficiency screening provided hypersensitive strains are then
      confirmed as such using purified active principles. 

PMID- 24569178
TI  - Functionalized graphene/silicon chemi-diode H2 sensor with tunable sensitivity.
AB  - A reverse bias tunable Pd- and Pt-functionalized graphene/Si heterostructure
      Schottky diode H2 sensor has been demonstrated. Compared to the graphene
      chemiresistor sensor, the chemi-diode sensor offers more than one order of
      magnitude higher sensitivity as the molecular adsorption induced Schottky barrier
      height change causes the heterojunction current to vary exponentially in reverse
      bias. The reverse bias operation also enables low power consumption, as well as
      modulation of the atomically thin graphene's Fermi level, leading to tunable
      sensitivity and detection of H2 down to the sub-ppm range.

PMID- 24569177
TI  - Polar lipids from the marine macroalga Palmaria palmata inhibit
      lipopolysaccharide-induced nitric oxide production in RAW264.7 macrophage cells.
AB  - The EtOAc soluble fraction of a MeOH/CHCl3 extract of Palmaria palmata showed
      strong nitric oxide (NO) inhibitory activity against lipopolysaccharide (LPS)
      induced NO production in murine RAW264.7 cells. NO inhibition-guided isolation
      led to identification of three new polar lipids including a sulfoquinovosyl
      diacylglycerol (SQDG) (2S)-1-O-eicosapentaenoyl-2-O-myristoyl-3-O-(6-sulfo-alpha
      D-quinovopyranosyl)-glycerol (1) and two phosphatidylglycerols, 1-O
      eicosapentaenoyl-2-O-trans-3-hexadecenoyl-3-phospho-(1'-glycerol)-glycerol (3)
      and 1-O-eicosapentaenoyl-2-O-palmitoyl-3-phospho-(1'-glycerol)-glycerol (4) from
      the EtOAc fraction. Seven known lipids were also isolated including a SQDG (2), a
      phospholipid (5) and five galactolipids (6-10). Structures of the isolated lipids
      were elucidated by spectral analyses. The isolated SQDGs, phosphatidylglycerols
      and phospholipid possessed strong and dose-dependent NO inhibitory activity
      compared to N(G)-methyl-L-arginine acetate salt (L-NMMA), a well-known NO
      inhibitor used as a positive control. Further study suggested that these polar
      lipids suppressed NO production through down-regulation of inducible nitric oxide
      synthase (iNOS).

PMID- 24569179
TI  - Self-efficacy for temptations is a better predictor of weight loss than
      motivation and global self-efficacy: evidence from two prospective studies among
      overweight/obese women at high risk of breast cancer.
AB  - OBJECTIVES: Identifying predictors of weight loss could help to triage people who
      will benefit most from programs and identify those who require additional
      support. The present research was designed to address statistical, conceptual and
      operational difficulties associated with the role of self-efficacy in predicting
      weight loss. METHODS: In Study 1, 115 dieting overweight/obese women at high risk
      of breast cancer were weighed and completed questionnaires assessing motivation,
      global self-efficacy and self-efficacy for temptations. The main outcome measure
      was weight, measured 3-months post-baseline. Study 2 was identical (n=107),
      except changes in psychological variables were computed, and used to predict
      weight 6-months post-baseline. RESULTS: In Study 1, self-efficacy for temptations
      was a significant predictor of weight loss at 3-month follow-up. In Study 2,
      improved self-efficacy for temptations between baseline and four-weeks was
      predictive of lower weight at 6 months. CONCLUSION: The key finding was that self
      efficacy for temptations, as opposed to motivation and global self-efficacy, was
      predictive of subsequent weight loss. PRACTICE IMPLICATIONS: The implication is
      that augmenting dieters' capability for dealing with temptations might boost the
      impact of weight loss programs.

PMID- 24569181
TI  - Should we search for linear correlations between global strain parameters and
      ejection fraction?

PMID- 24569180
TI  - "They just say everything's a virus"--parent's judgment of the credibility of
      clinician communication in primary care consultations for respiratory tract
      infections in children: a qualitative study.
AB  - OBJECTIVE: To investigate parents' experiences and views of clinician
      communication during primary care consultations for respiratory tract infections
      (RTIs) in children under 12. METHODS: Semi-structured interviews with 30 parents
      who had recently consulted for RTI in their child. Purposive sampling was used to
      interview parents from a range of socio-economic areas. RESULTS: Parents
      critically assess the credibility of primary care clinician diagnosis and
      treatment recommendations based on their perception of the medical evaluation and
      how well their concerns and expectations have been addressed. A "viral" diagnosis
      could be perceived as trivializing, particularly when contradicting the parent's
      perception of severity. Parents expected advice on symptomatic treatment and felt
      frustrated by 'no treatment' recommendations. Parents commonly reported safety
      netting advice which was too vague to be useful. CONCLUSION: Parents' perception
      of the credibility of the diagnosis and treatment recommendations is influenced
      both by their expectations and the effectiveness of clinician communication.
      Opportunities are being missed to inform parents about symptomatic care and when
      to consult for children with RTIs. PRACTICE IMPLICATIONS: Clinicians should
      tailor diagnostic explanations to parental expectations and concerns and address
      the symptoms of significance to parents. Clinicians should provide advice about
      symptom relief and more precise safety netting advice.

PMID- 24569182
TI  - EuroEcho-Imaging 2013: highlights.
AB  - The annual meeting of the European Association of Echocardiography (EuroEcho
      Imaging) was held in Istanbul, Turkey. In the present paper, we present a summary
      of the 'Highlights' session. 

PMID- 24569221
TI  - Factors affecting the ability of baclofen to reduce fat intake in rats.
AB  - The GABA-B agonist baclofen has been reported to reduce the consumption of
      vegetable shortening, but not lard, in rats. This study sought to examine some of
      the factors that could account for these differences. Baclofen (0, 1.0, 1.8, 3.2
      mg/kg, intraperitoneal) was tested: (i) on shortening and lard intake, (ii) under
      'binge-type' and non-'binge-type' conditions, (iii) when each fat was presented
      alone or simultaneously, and (iv) with a 30-min or no pretreatment time. With a
      30-min pretreatment time, baclofen (3.2 mg/kg, intraperitoneal) consistently
      reduced shortening intake under 'binge-type' and non-'binge-type' conditions, as
      well as when shortening was presented alone or when lard was simultaneously
      available. Baclofen also reduced lard intake under 'binge-type' and non-'binge
      type' conditions, but only when lard was presented alone. Baclofen had no effect
      on chow intake. When each fat was presented alone, and with no pretreatment time,
      the results were less consistent; baclofen reduced shortening intake only under
      non-'binge-type' conditions, and lard intake only under 'binge-type' conditions,
      and also stimulated chow intake. In summary, the type of fat, the presentation
      mode (one fat presented alone or two fats simultaneously), and the time between
      baclofen administration and intake all influence the ability of baclofen to
      reduce fat intake. 

PMID- 24569224
TI  - Comparison of two commercial rapid in-clinic serological tests for detection of
      antibodies against Leishmania spp. in dogs.
AB  - Antibodies against Leishmania spp. are detected in most dogs with clinical signs
      of leishmaniasis due to Leishmania infantum. Accurate, rapid in-clinic
      serological tests may permit immediate confirmation of the diagnosis and
      implementation of therapeutic measures. The aim of the current study was to
      evaluate the diagnostic accuracy of 2 commercial, rapid in-clinic serological
      tests for the detection of anti-Leishmania antibodies in sera of dogs, the Snap
      Canine Leishmania Antibody Test kit (IDEXX Laboratories Inc., Westbrook, Maine)
      and the ImmunoRun Antibody Detection kit (Biogal Galed Labs, Kibbutz Galed,
      Israel), using indirect fluorescent antibody test (IFAT) as the reference method.
      A total of 109 sera collected from 65 seropositive and 44 seronegative dogs were
      used. The sensitivities of the Snap and ImmunoRun kits were 89.23% (95%
      confidence interval: 79.05-95.54%) and 86.15% (95% confidence interval: 75.33
      93.45%), respectively, and the specificity of both tests was 100%. A good
      agreement between each of the rapid in-clinic serological tests and IFAT and
      between the 2 rapid in-clinic serological tests was witnessed. Both rapid in
      clinic serological tests showed an adequate diagnostic accuracy and can be used
      for the fast detection of antibodies against L. infantum in dogs. 

PMID- 24569225
TI  - Establishment of an agamid cell line and isolation of adenoviruses from central
      bearded dragons (Pogona vitticeps).
AB  - A cell line was established from whole 6-8-week-old central bearded dragon
      (Pogona vitticeps) embryos. Cells were mid-sized and showed an elongated and
      polymorphic form. The cell line grew in a monolayer and has been serially
      passaged for 17 passages at time of publication. This cell line has been used
      with samples from adenovirus polymerase chain reaction (PCR)-positive bearded
      dragons, and 2 virus isolates have been obtained so far. The isolates show a
      clear cytopathic effect in inoculated cells. Both virus isolates have been
      serially passaged on this cell line, and have been identified by PCR
      amplification and sequencing of a portion of the DNA-dependent DNA polymerase
      gene and show 100% nucleotide identity to the corresponding region of an agamid
      adenovirus. Electron microscopic examination of supernatant from infected cells
      demonstrated the presence of nonenveloped particles, with a diameter of
      approximately 80 nm in both virus isolates. 

PMID- 24569226
TI  - When grief turns into love: understanding the experience of parents who have
      revived after losing a child due to cancer.
AB  - A child's death caused by cancer generates a deep impact on his/her parents, who
      can be affected by serious health problems due to an impairment of their
      lifestyle. Notwithstanding their suffering, some parents manage to overcome it
      and discover a new meaning for their lives. The goal of this phenomenological
      study is to understand the lived experiences that help parents to revive after
      the death of their child due to cancer. The participants were fathers and mothers
      who believe that they have elaborated their mourning. Their lived experiences
      were collected in interviews they had previously agreed to give. The question
      that steered the interview was: "What is the experience you went through that
      helped you to revive after your child died due to cancer?" Data were analyzed
      using Streubert's method. Analyzing the interviews of the participants, 3
      interweaved essences were detected: transition from surviving to reviving
      themselves; ascribing a sense and meaning to the life, agony, and death of a
      child; and helping other parents through one's own experience. 

PMID- 24569222
TI  - Crosstalk between ubiquitin and other post-translational modifications on
      chromatin during double-strand break repair.
AB  - The cellular response to DNA double-stranded breaks (DSBs) involves a conserved
      mechanism of recruitment and activation of numerous proteins involved in this
      pathway. The events that trigger this response in mammalian cells involve several
      post-translational modifications, but the role of non-proteasomal ubiquitin
      signaling is particularly central to this pathway. Recent work has demonstrated
      that ubiquitination does not act alone, but in concert with other post
      translational modifications, including phosphorylation, methylation, acetylation,
      ADP-ribosylation, and other ubiquitin-like modifiers, particularly SUMOylation.
      We review novel and exciting crosstalk mechanisms between ubiquitination and
      other post-translational modifications, many of which work synergistically with
      each other to activate signaling events and help recruit important DNA damage
      effector proteins, particularly BRCA1 (breast cancer 1, early onset) and 53BP1
      (tumor protein p53 binding protein 1), to sites of DNA damage. 

PMID- 24569227
TI  - Caregivers' perception of drug administration safety for pediatric oncology
      patients.
AB  - Medication errors (MEs) are reported to be between 1.5% and 90% depending on many
      factors, such as type of the institution where data were collected and the method
      to identify the errors. More significantly, the risk for errors with potential
      for harm is 3 times higher for children, especially those receiving chemotherapy.
      Few studies have been published on averting such errors with children and none on
      how caregivers perceive their role in preventing such errors. The purpose of this
      study was to evaluate pediatric oncology patient's caregivers' perception of drug
      administration safety and their willingness to be involved in averting such
      errors. A cross-sectional design was used to study a nonrandomized sample of 100
      caregivers of pediatric oncology patients. Ninety-six of the caregivers surveyed
      were well informed about the medications their children receive and were ready to
      participate in error prevention strategies. However, an underestimation of
      potential errors uncovered a high level of "trust" for the staff. Caregivers
      echoed their apprehension for being responsible for potential errors. Caregivers
      are a valuable resource to intercept medication errors. However, caregivers may
      be hesitant to actively communicate their fears with health professionals.
      Interventions that aim at encouraging caregivers to engage in the safety of their
      children are recommended. 

PMID- 24569230
TI  - Managing lipid metabolism in proliferating cells: new perspective for metformin
      usage in cancer therapy.
AB  - Cancer cells metabolically adapt to undergo cellular proliferation. Lipids,
      besides their well-known role as energy storage, represent the major building
      blocks for the synthesis of neo-generated membranes. There is increasing evidence
      that cancer cells show specific alterations in different aspects of lipid
      metabolism. The changes of expression and activity of lipid metabolising enzymes
      are directly regulated by the activity of oncogenic signals. The dependence of
      tumour cells on the deregulated lipid metabolism suggests that proteins involved
      in this process could be excellent chemotherapeutic targets for cancer treatment.
      Due to its rare side effects in non-cancerous cells, metformin has been recently
      revaluated as a potential anti-tumourigenic drug, which negatively affects lipid
      biosynthetic pathways. In this review we summarised the emerging molecular events
      linking the anti-proliferative effect of metformin with lipid metabolism in
      cancer cells. 

PMID- 24569231
TI  - Young living liver donors: a single-center perspective.

PMID- 24569233
TI  - Intratumoral heterogeneity in kidney cancer.
AB  - Clear cell renal cell carcinoma (CCRCC) is characterized by mutation of the VHL
      gene and loss of a segment of chromosome 3. A new study using multi-region exome
      sequencing has identified substantial intratumoral heterogeneity within large
      primary CCRCCs, which has profound implications for understanding tumor evolution
      and for developing effective therapies. 

PMID- 24569228
TI  - Regulation of microRNAs in cancer metastasis.
AB  - Metastasis is a phenomenon of crucial importance in defining prognosis in
      patients with cancer and is often responsible for cancer-related mortality. It is
      known that several steps are necessary for clonal cells to disseminate from their
      primary tumor site and colonize distant tissues, thus originating metastatic
      lesions. Therefore, investigating the molecular actors regulating this process
      may provide helpful insights in the development of efficient therapeutic
      responses. Recent evidences have indicated the role of microRNAs (miRNAs) in
      modulating the metastatic process in solid tumors. miRNAs are small regulatory
      non-coding RNAs that bind to specific target mRNAs, leading to translational
      repression. miRNAs are known to act as negative regulators of gene expression and
      are involved in the regulation of biological processes, including cell growth,
      differentiation and apoptosis, both in physiological conditions and during
      diseases, such as tumors. In the specific field of tumorigenesis, miRNAs play an
      important role in mediating oncogenesis and favoring tumor progression, as a
      result of their ability to modulate epithelial-to-mesenchymal transition (EMT)
      and other series of events facilitating the formation of metastasis. The role of
      miRNAs in cancer development has been widely studied and has helped elucidate
      events such as the change in expression of oncogenes, tumor-suppressors and
      cancer-related proteins. This review focuses on the mechanisms underlying the
      role of miRNAs as part of the metastatic process. 

PMID- 24569234
TI  - The epigenetic sole of sex and dosage compensation.
AB  - Sex chromosomes in mammals, birds, reptiles and fish represent many independent
      evolutionary events, but there is spectacular convergence and stunning parallels.
      A new study details the early stages of ZW differentiation and sex determination
      in a flatfish and the establishment of dosage compensation and sex reversal by
      epigenetic mechanisms including DNA methylation. 

PMID- 24569235
TI  - Stem cell fate regulation by dynein motor protein Lis1.
AB  - Cell fate regulation is a central component of maintaining tissue homeostasis,
      yet the mechanisms instructing cell division diversity in tissue-specific stem
      cells have not been well understood. A new study uncovers a central role for
      microtubule motor-regulating protein Lis1 in hematopoietic stem cell fate
      determination and in leukemogenesis. 

PMID- 24569242
TI  - Phenotype and disease course of early-onset pediatric inflammatory bowel disease.
AB  - BACKGROUND: Early-onset (EO) pediatric inflammatory bowel diseases (IBD) seem to
      be more extensive than those with a later onset. To test this hypothesis, we
      examined the phenotype and disease course of patients with IBD diagnosis at 0 to
      5 years, compared with the ranges 6 to 11 and 12 to 18 years. METHODS: Anatomic
      locations and behaviors were assessed according to Paris classification in 506
      consecutive patients: 224 Crohn's disease, 245 ulcerative colitis, and 37 IBD
      unclassified. RESULTS: Eleven percent of patients were in the range 0 to 5 years,
      39% in 6 to 11 years, and 50% in 12 to 18 years. Ulcerative colitis was the most
      frequent diagnosis in EO-IBD and in 6- to 11-year-old group, whereas Crohn's
      disease was predominant in older children. A classification as IBD-unclassified
      was more common in the range 0 to 5 years compared with the other groups (P <
      0.005). EO Crohn's disease showed a more frequent isolated colonic (P < 0.005)
      and upper gastrointestinal involvement than later-onset disease. Sixty-two
      percent of the patients in the 0 to 5 years range had pancolonic ulcerative
      colitis, compared with 38% of 6 to 11 years (P = 0.02) and 31% of 12-18 years (P
      = 0.002) range. No statistical difference for family history for IBD was found in
      the 3-year age groups. Therapies at the diagnosis were similar for all children.
      However, at latest follow-up, a significantly higher proportion of younger
      children were under steroids compared with older groups (P < 0.05). Surgical risk
      did not differ according to age. CONCLUSIONS: EO-IBD exhibits an extensive
      phenotype and benefit from aggressive treatment strategies, although surgical
      risk is similar to later-onset disease. A family history for IBD is not common in
      EO disease.

PMID- 24569243
TI  - Optically transparent piezoelectric transducer for ultrasonic particle
      manipulation.
AB  - We report an optically transparent ultrasonic device, consisting of indium-tin
      oxide-coated lithium niobate (LNO), for use in particle manipulation. This device
      shows good transparency in the visible and near-infrared wavelengths and,
      acoustically, compares favorably with conventional prototype devices with silver
      electrodes. 

PMID- 24569244
TI  - Electrode position optimization in magnetoelectric sensors based on
      magnetostrictive-piezoelectric bilayers on cantilever substrates.
AB  - Finite element method (FEM) simulations are performed to investigate the
      sensitivity to dc magnetic fields of magnetoelectric sensors on cantilever
      substrates with trenches or weights at different positions. For a simple layered
      cantilever, a 15% higher signal voltage across the piezoelectric layer is
      obtained for optimally positioned electrodes and an insulating magnetostrictive
      material. A further 25% increase in the signal voltage is achieved for a trenched
      cantilever design with a pick-up region. 

PMID- 24569229
TI  - Functional characterization of Anaphase Promoting Complex/Cyclosome (APC/C) E3
      ubiquitin ligases in tumorigenesis.
AB  - The Anaphase Promoting Complex/Cyclosome (APC/C) is a multi-subunit E3 ubiquitin
      ligase that primarily governs cell cycle progression. APC/C is composed of at
      least 14 core subunits and recruits its substrates for ubiquitination via one of
      the two adaptor proteins, Cdc20 or Cdh1, in M or M/early G1 phase, respectively.
      Furthermore, recent studies have shed light on crucial functions for APC/C in
      maintaining genomic integrity, neuronal differentiation, cellular metabolism and
      tumorigenesis. To gain better insight into the in vivo physiological functions of
      APC/C in regulating various cellular processes, particularly development and
      tumorigenesis, a number of mouse models of APC/C core subunits, coactivators or
      inhibitors have been established and characterized. However, due to their
      essential role in cell cycle regulation, most of the germline knockout mice
      targeting the APC/C pathway are embryonic lethal, indicating the need for
      generating conditional knockout mouse models to assess the role in tumorigenesis
      for each APC/C signaling component in specific tissues. In this review, we will
      first provide a brief introduction of the ubiquitin-proteasome system (UPS) and
      the biochemical activities and cellular functions of the APC/C E3 ligase. We will
      then focus primarily on characterizing genetic mouse models used to understand
      the physiological roles of each APC/C signaling component in embryogenesis, cell
      proliferation, development and carcinogenesis. Finally, we discuss future
      research directions to further elucidate the physiological contributions of APC/C
      components during tumorigenesis and validate their potentials as a novel class of
      anti-cancer targets. 

PMID- 24569246
TI  - An efficient block matching and spectral shift estimation algorithm with
      applications to ultrasound elastography.
AB  - An efficient block matching and spectral shift estimation algorithm for freehand
      quasi-static ultrasound elastography is described in this paper. The proposed
      method provides a balance between computational speed and robustness against
      displacement estimation error and bias; a fundamental aspect of elastography. The
      new algorithm was tested on an extensive set of simulated 1-D RF ultrasound
      signals, replicating various strain profiles. Additionally, real 2-D scans were
      conducted on an ultrasound phantom with prescribed elastic properties; the
      algorithm output was further validated with a comparison to a finite element
      model (FEM) of the phantom. Clinical data from a breast cancer study and
      histology slides were used to demonstrate the in vivo use of the new elastography
      technique. The algorithm showed a significant computational savings (at least 60
      times faster) over existing spectral shift analysis methods. Accurate strain
      images were produced in as little as 2 s with the scope for further speed
      enhancements through parallel processing; making real-time implementation a
      future possibility. Moreover, it demonstrated a robustness toward displacement
      estimation error when compared with conventional gradient-based techniques, and
      was able to perform at high strain values (>5%) while showing relative
      insensitivity to various parameters settings, such as sample rate and block
      window size; a desirable performance for a practical clinical tool. 

PMID- 24569245
TI  - Cell membrane deformation induced by a fibronectin-coated polystyrene microbead
      in a 200-MHz acoustic trap.
AB  - The measurement of cell mechanics is crucial for a better understanding of
      cellular responses during the progression of certain diseases and for the
      identification of the cell's nature. Many techniques using optical tweezers,
      atomic force microscopy, and micro-pipettes have been developed to probe and
      manipulate cells in the spatial domain. In particular, we recently proposed a two
      dimensional acoustic trapping method as an alternative technique for small
      particle manipulation. Although the proposed method may have advantages over
      optical tweezers, its applications to cellular mechanics have not yet been
      vigorously investigated. This study represents an initial attempt to use acoustic
      tweezers as a tool in the field of cellular mechanics in which cancer cell
      membrane deformability is studied. A press-focused 193-MHz single-element lithium
      niobate (LiNbO3) transducer was designed and fabricated to trap a 5-MUm
      polystyrene microbead near the ultrasound beam focus. The microbeads were coated
      with fibronectin, and trapped before being attached to the surface of a human
      breast cancer cell (MCF-7). The cell membrane was then stretched by remotely
      pulling a cell-attached microbead with the acoustic trap. The maximum cell
      membrane stretched lengths were measured to be 0.15, 0.54, and 1.41 MUm at input
      voltages to the transducer of 6.3, 9.5, and 12.6 Vpp, respectively. The stretched
      length was found to increase nonlinearly as a function of the voltage input. No
      significant cytotoxicity was observed to result from the bead or the trapping
      force on the cell during or after the deformation procedure. Hence, the results
      convincingly demonstrated the possible application of the acoustic trapping
      technique as a tool for cell manipulation. 

PMID- 24569247
TI  - Simulation-based validation for four- dimensional multi-channel ultrasound
      current source density imaging.
AB  - Ultrasound current source density imaging (UCSDI), which has application to the
      heart and brain, exploits the acoustoelectric (AE) effect and Ohm's law to detect
      and map an electrical current distribution. In this study, we describe 4-D UCSDI
      simulations of a dipole field for comparison and validation with bench-top
      experiments. The simulations consider the properties of the ultrasound pulse as
      it passes through a conductive medium, the electric field of the injected dipole,
      and the lead field of the detectors. In the simulation, the lead fields of
      detectors and electric field of the dipole were calculated by the finite element
      (FE) method, and the convolution and correlation in the computation of the
      detected AE voltage signal were accelerated using 3-D fast Fourier transforms. In
      the bench-top experiment, an electric dipole was produced in a bath of 0.9% NaCl
      solution containing two electrodes, which injected an ac pulse (200 Hz, 3 cycles)
      ranging from 0 to 140 mA. Stimulating and recording electrodes were placed in a
      custom electrode chamber made on a rapid prototype printer. Each electrode could
      be positioned anywhere on an x-y grid (5 mm spacing) and individually adjusted in
      the depth direction for precise control of the geometry of the current sources
      and detecting electrodes. A 1-MHz ultrasound beam was pulsed and focused through
      a plastic film to modulate the current distribution inside the saline-filled
      tank. AE signals were simultaneously detected at a sampling frequency of 15 MHz
      on multiple recording electrodes. A single recording electrode is sufficient to
      form volume images of the current flow and electric potentials. The AE potential
      is sensitive to the distance from the dipole, but is less sensitive to the angle
      between the detector and the dipole. Multi-channel UCSDI potentially improves 4-D
      mapping of bioelectric sources in the body at high spatial resolution, which is
      especially important for diagnosing and guiding treatment of cardiac and
      neurologic disorders, including arrhythmia and epilepsy.

PMID- 24569248
TI  - Ultrasonic multipath and beamforming clutter reduction: a chirp model approach.
AB  - In vivo ultrasonic imaging with transducer arrays suffers from image degradation
      resulting from beamforming limitations, including diffraction-limited beamforming
      and beamforming degradation caused by tissue inhomogeneity. Additionally, based
      on recent studies, multipath scattering also causes significant image
      degradation. To reduce degradation from both sources, we propose a model-based
      signal decomposition scheme. The proposed algorithm identifies spatial frequency
      signatures to decompose received wavefronts into their most significant
      scattering sources. Scattering sources originating from a region of interest are
      used to reconstruct decluttered wavefronts, which are beamformed into decluttered
      RF scan lines or A-lines. To test the algorithm, ultrasound system channel data
      were acquired during liver scans from 8 patients. Multiple data sets were
      acquired from each patient, with 55 total data sets, 43 of which had identifiable
      hypoechoic regions on normal B-mode images. The data sets with identifiable
      hypoechoic regions were analyzed. The results show the decluttered B-mode images
      have an average improvement in contrast over normal images of 7.3 +/- 4.6 dB. The
      contrast-to-noise ratio (CNR) changed little on average between normal and
      decluttered Bmode, -0.4 +/- 5.9 dB. The in vivo speckle SNR decreased; the change
      was -0.65 +/- 0.28. Phantom speckle SNR also decreased, but only by -0.40 +/-
      0.03.

PMID- 24569250
TI  - Ultrasound-guided photoacoustic imaging: current state and future development.
AB  - Photoacoustic imaging, frequently coregistered with ultrasonic imaging, can
      provide functional and cellular/molecular information about tissue within the
      anatomical landmarks of an imaged region. This review details the fundamentals of
      photoacoustic imaging and its most promising imaging applications. Particular
      attention is paid to photoacoustic imaging's relationship with ultrasound,
      focusing on distinct differences and similarities between the two modalities and
      highlighting the mutual benefit of using both concurrently in certain preclinical
      and clinical applications. Much like its origins as an imaging modality were
      intertwined with ultrasonic imaging (namely, its acoustic transducers and
      hardware), the future of photoacoustic imaging-particularly in the clinical arena
      similarly depends on ultrasound and its time-tested ability to provide real-time
      visualization of soft tissue.

PMID- 24569249
TI  - An IVUS transducer for microbubble therapies.
AB  - There is interest in examining the potential of modified intravascular ultrasound
      (IVUS) catheters to facilitate dual diagnostic and therapeutic roles using
      ultrasound plus microbubbles for localized drug delivery to the vessel wall. The
      goal of this study was to design, prototype, and validate an IVUS transducer for
      microbubble-based drug delivery. A 1-D acoustic radiation force model and finite
      element analysis guided the design of a 1.5-MHz IVUS transducer. Using the IVUS
      transducer, biotinylated microbubbles were displaced in water and bovine whole
      blood to the streptavidin-coated wall of a flow phantom by a 1.5-MHz center
      frequency, peak negative pressure = 70 kPa pulse with varying pulse repetition
      frequency (PRF) while monitoring microbubble adhesion with ultrasound. A fit was
      applied to the RF data to extract a time constant (tau). As PRF was increased in
      water, the time constant decreased (tau = 32.6 s, 1 kHz vs. tau = 8.2 s, 6 kHz),
      whereas in bovine whole blood an adhesion-no adhesion transition was found for
      PRFs >= 8 kHz. Finally, a fluorophore was delivered to an ex vivo swine artery
      using microbubbles and the IVUS transducer, resulting in a 6.6-fold increase in
      fluorescence. These results indicate the importance of PRF (or duty factor) for
      IVUS acoustic radiation force microbubble displacement and the potential for IVUS
      and microbubbles to provide localized drug delivery.

PMID- 24569251
TI  - Self-characterization of commercial ultrasound probes in transmission acoustic
      inverse scattering: transducer model and volume integral formulation.
AB  - A self-contained source characterization method for commercial ultrasound probes
      in transmission acoustic inverse scattering is derived and experimentally tested.
      The method is based on modified scattered field volume integral equations that
      are linked to the source-scattering transducer model. The source-scattering
      parameters are estimated via pair-wise transducer measurements and the nonlinear
      inversion of an acoustic propagation model that is derived. This combination
      creates a formal link between the transducer characterization and the inverse
      scattering algorithm. The method is tested with two commercial ultrasound probes
      in a transmission geometry including provisions for estimating the probe
      locations and aligning a robotic rotator. The transducer characterization results
      show that the nonlinear inversion fit the measured data well. The transducer
      calibration and inverse scattering algorithm are tested on simple targets.
      Initial images show that the recovered contrasts are physically consistent with
      expected values. 

PMID- 24569252
TI  - Review of high-power ultrasound-industrial applications and measurement methods.
AB  - Applications involving high-power ultrasound are expanding rapidly as ultrasonic
      intensification opportunities are identified in new fields. This is facilitated
      through new technological developments and an evolution of current systems to
      tackle challenging problems. It is therefore important to continually update both
      the scientific and commercial communities on current system performance and
      limitations. To achieve this objective, this paper addresses two key aspects of
      high-power ultrasonic systems. In the first part, the review of high-power
      applications focuses on industrial applications and documents the developing
      technology from its early cleaning applications through to the advanced
      sonochemistry, cutting, and water treatment applications used today. The second
      part provides a comprehensive overview of measurement techniques used in
      conjunction with high-power ultrasonic systems. This is an important and evolving
      field which enables design and process engineers to optimize the behavior and/or
      operation of key metrics of system performance, such as field distribution or
      cavitation intensity. 

PMID- 24569253
TI  - Application of conformal map theory for design of 2-D ultrasonic array structure
      for NDT imaging application: a feasibility study.
AB  - Two-dimensional ultrasonic phased arrays are becoming increasingly popular in
      nondestructive evaluation (NDE). Sparse array element configurations are required
      to fully exploit the potential benefits of 2-D phased arrays. This paper applies
      the conformal mapping technique as a means of designing sparse 2-D array layouts
      for NDE applications. Modeling using both Huygens' field prediction theory and 2
      D fast Fourier transformation is employed to study the resulting new structure. A
      conformal power map was used that, for fixed beam width, was shown in simulations
      to have a greater contrast than rectangular or random arrays. A prototype
      aperiodic 2-D array configuration for direct contact operation in steel, with
      operational frequency ~3 MHz, was designed using the array design principle
      described in this paper. Experimental results demonstrate a working sparse-array
      transducer capable of performing volumetric imaging.

PMID- 24569254
TI  - Acoustic precursor wave propagation in viscoelastic media.
AB  - Precursor field theory has been developed to describe the dynamics of
      electromagnetic field evolution in causally attenuative and dispersive media. In
      Debye dielectrics, the so-called Brillouin precursor exhibits an algebraic
      attenuation rate that makes it an ideal pulse waveform for communication,
      sensing, and imaging applications. Inspired by these studies in the
      electromagnetic domain, the present paper explores the propagation of acoustic
      precursors in dispersive media, with emphasis on biological media. To this end, a
      recently proposed causal dispersive model is employed, based on its
      interpretation as the acoustic counterpart of the Cole?Cole model for
      dielectrics. The model stems from the fractional stress?strain relation, which is
      consistent with the empirically known frequency power-law attenuation in
      viscoelastic media. It is shown that viscoelastic media described by this model,
      including human blood, support the formation and propagation of Brillouin
      precursors. The amplitude of these precursors exhibits a sub-exponential
      attenuation rate as a function of distance, actually being proportional to z(-p),
      where z is the distance traveled within the medium and 0.5 <p < 1. The precursors
      identified in this work facilitate the design of optimal waveforms for
      propagation in complex media, creating new possibilities for acoustic-pulse-based
      communication and imaging systems.

PMID- 24569255
TI  - An improved wave-vector frequency-domain method for nonlinear wave modeling.
AB  - In this paper, a recently developed wave-vector frequency-domain method for
      nonlinear wave modeling is improved and verified by numerical simulations and
      underwater experiments. Higher order numeric schemes are proposed that
      significantly increase the modeling accuracy, thereby allowing for a larger step
      size and shorter computation time. The improved algorithms replace the left-point
      Riemann sum in the original algorithm by the trapezoidal or Simpson's
      integration. Plane waves and a phased array were first studied to numerically
      validate the model. It is shown that the left-point Riemann sum, trapezoidal, and
      Simpson's integration have first-, second-, and third-order global accuracy,
      respectively. A highly focused therapeutic transducer was then used for
      experimental verifications. Short high-intensity pulses were generated. 2-D scans
      were conducted at a prefocal plane, which were later used as the input to the
      numerical model to predict the acoustic field at other planes. Good agreement is
      observed between simulations and experiments.

PMID- 24569256
TI  - Sensitivity analysis of multi-layered C-axis inclined zigzag zinc oxide thin-film
      resonators as viscosity sensors.
AB  - This paper presents a theoretical analysis of a new zigzag C-axis inclined multi
      layer ZnO thin-film bulk acoustic wave resonator (FBAR) as a viscosity sensor to
      monitor the lubrication performance of engine oil and other liquids. Free
      vibration and forced vibration for the FBAR loaded with liquids are analyzed.
      Equations necessary to calculate the sensitivity are derived. The numerical
      analysis shows that as the number of layers increases, the absolute sensitivity
      increases as well. The influences on the sensitivity of C-axis inclined angle, Q
      factor, and thickness are also investigated. The results provide a foundation for
      further design of multi-layer FBAR viscosity sensors. 

PMID- 24569257
TI  - Design and optimization of a modal- independent linear ultrasonic motor.
AB  - To simplify the design of the linear ultrasonic motor (LUSM) and improve its
      output performance, a method of modal decoupling for LUSMs is proposed in this
      paper. The specific embodiment of this method is decoupling of the traditional
      LUSM stator's complex vibration into two simple vibrations, with each vibration
      implemented by one vibrator. Because the two vibrators are designed
      independently, their frequencies can be tuned independently and frequency
      consistency is easy to achieve. Thus, the method can simplify the design of the
      LUSM. Based on this method, a prototype modal- independent LUSM is designed and
      fabricated. The motor reaches its maximum thrust force of 47 N, maximum unloaded
      speed of 0.43 m/s, and maximum power of 7.85 W at applied voltage of 200 Vpp. The
      motor's structure is then optimized by controlling the difference between the two
      vibrators' resonance frequencies to reach larger output speed, thrust, and power.
      The optimized results show that when the frequency difference is 73 Hz, the
      output force, speed, and power reach their maximum values. At the input voltage
      of 200 Vpp, the motor reaches its maximum thrust force of 64.2 N, maximum
      unloaded speed of 0.76 m/s, maximum power of 17.4 W, maximum thrust-weight ratio
      of 23.7, and maximum efficiency of 39.6%.

PMID- 24569258
TI  - Lead zirconate titanate-based thick films for high-frequency focused ultrasound
      transducers prepared by electrophoretic deposition.
AB  - An electrophoretic deposition (EPD) process with high deposition rate was used to
      fabricate a curved piezoelectric thick film devoted to high-frequency transducers
      for medical imaging. Niobium-doped lead zirconate titanate (PZTNb) powder was
      stabilized in ethanol to prepare a suspension with high zeta potential and low
      conductivity. A gold layer, pad-printed and fired on a curved porous PZT
      substrate, was used as the working electrode for the deposition of the PZTNb
      thick film. This substrate was chosen because it has the required properties
      (acoustic impedance and attenuation) to be used directly as a backing for the
      high-frequency transducer, leading to a simplified process for transducer
      assembly with this integrated structure. PZT-Nb thick films were also deposited
      by EPD on flat gold-coated alumina substrates as a reference. The thickness of
      the films was between 20 and 35 MUm, and their electromechanical performance was
      comparable to standard PZT bulk ceramics with a thickness coupling factor of 48%.
      For the curved thick film, the thickness coupling factor was slightly lower. The
      corresponding integrated structure was used to fabricate a transducer with a
      center frequency of 40 MHz and an f-number of 2.8. It was integrated into a
      realtime ultrasound scanner and used to image human forearm skin; the resulting
      images showed, for the first time, the efficacy of the EPD process for these
      imaging applications.

PMID- 24569259
TI  - Supraventricular tachycardia precipitated by a peripherally inserted central
      catheter in an infant with gastroschisis.
AB  - Gastroschisis is a common congenital abdominal wall defect requiring surgical
      correction in early neonatal life. The time to full enteral feeds among infants
      with gastroschisis is variable. Gastroschisis remains a common surgical cause of
      intestinal failure in neonates. Peripherally inserted central catheters (PICC)
      are commonly used to provide long-term venous access for parenteral nutrition
      during the time enteral feeds are being slowly established. The PICC is placed
      under fluoroscopic guidance with the distal end of the catheter usually placed at
      the junction of the superior vena cava with the right atrium. In rare
      circumstances, the catheter tip may advance into intracardiac chambers,
      precipitating supraventricular re-entrant tachycardia. We report a case of an
      infant who was antenatally diagnosed with uncomplicated gastroschisis in whom a
      supraventricular tachycardia was precipitated by the PICC in the right atrium. 

PMID- 24569260
TI  - Hypercalcaemia: atypical presentation of miliary tuberculosis.
AB  - We report an unusual case of miliary tuberculosis in a 77-year-old Filipino man
      with hypertension, diabetes mellitus, nephrolithiasis status-post left
      nephrectomy, presenting with 1 month of fever, generalised weakness and weight
      loss. Laboratory data were significant for anaemia, hypercalcaemia and acute
      kidney injury. Chest radiograph showed ground glass opacities and interstitial
      infiltrates. Extensive workup was performed to evaluate fever and hypercalcaemia.
      Malignancy, hormonal and septic workup were all unremarkable. Tuberculin skin
      test was negative. Sputum, pleural fluid, bronchoalveolar lavage and
      cerebrospinal fluid were acid-fast bacilli (AFB) smear negative. Remarkably,
      urine AFB smear was positive. Caseating granulomas were seen on transbronchial
      biopsy. Antituberculosis therapy was initiated which lead to defervescence and
      initial clinical improvement. However, hospital course became complicated by
      small bowel obstruction and respiratory failure. He subsequently developed
      pulseless electrical activity and expired. An autopsy confirmed the presence of
      tuberculosis in multiple organs including his remaining kidney. 

PMID- 24569261
TI  - Ketoacidosis is not always due to diabetes.
AB  - Chronic alcoholism is a frequently unrecognised cause of ketoacidosis. Most
      patients with alcoholic ketoacidosis present with normal or low glucose, but this
      condition can present with hyperglycaemia. This can lead to misdiagnosis of
      diabetes ketoacidosis and, therefore, inappropriate treatment with insulin. We
      describe a 37-year-old Caucasian woman with chronic pancreatitis secondary to
      excess alcohol consumption, admitted with abdominal pain and vomiting, fulfilling
      the criteria for diabetes ketoacidosis. She was treated according to diabetes
      ketoacidosis protocol and experienced a hypoglycaemic attack within an hour of
      initiation of insulin. On review of her history, she was found to have three
      similar episodes over the past 12 months. Alcoholic ketoacidosis can present with
      hyperglycaemia due to relative deficiency of insulin and relative surplus in
      counter-regulatory stress hormones including glucagon. Awareness of the syndrome
      with a detailed history helps to differentiate alcohol ketoacidosis from diabetes
      ketoacidosis and prevent iatrogenic hypoglycaemia. 

PMID- 24569262
TI  - Novel anti-B-cell maturation antigen antibody-drug conjugate (GSK2857916)
      selectively induces killing of multiple myeloma.
AB  - B-cell maturation antigen (BCMA), highly expressed on malignant plasma cells in
      human multiple myeloma (MM), has not been effectively targeted with therapeutic
      monoclonal antibodies. We here show that BCMA is universally expressed on the MM
      cell surface and determine specific anti-MM activity of J6M0-mcMMAF (GSK2857916),
      a novel humanized and afucosylated antagonistic anti-BCMA antibody-drug conjugate
      via a noncleavable linker. J6M0-mcMMAF specifically blocks cell growth via G2/M
      arrest and induces caspase 3-dependent apoptosis in MM cells, alone and in
      coculture with bone marrow stromal cells or various effector cells. It strongly
      inhibits colony formation by MM cells while sparing surrounding BCMA-negative
      normal cells. J6M0-mcMMAF significantly induces effector cell-mediated lysis
      against allogeneic or autologous patient MM cells, with increased potency and
      efficacy compared with the wild-type J6M0 without Fc enhancement. The antibody
      dependent cell-mediated cytotoxicity and apoptotic activity of J6M0-mcMMAF is
      further enhanced by lenalidomide. Importantly, J6M0-mcMMAF rapidly eliminates
      myeloma cells in subcutaneous and disseminated mouse models, and mice remain
      tumor-free up to 3.5 months. Furthermore, J6M0-mcMMAF recruits macrophages and
      mediates antibody-dependent cellular phagocytosis of MM cells. Together, these
      results demonstrate that GSK2857916 has potent and selective anti-MM activities
      via multiple cytotoxic mechanisms, providing a promising next-generation
      immunotherapeutic in this cancer. 

PMID- 24569263
TI  - Long-term outcome with dasatinib after imatinib failure in chronic-phase chronic
      myeloid leukemia: follow-up of a phase 3 study.
AB  - We present long-term follow-up of a dasatinib phase 3 study of patients with
      imatinib-resistant/-intolerant chronic myeloid leukemia (CML). In the CA180-034
      study, 670 patients with imatinib-resistant/-intolerant CML in chronic phase (CML
      CP) received dasatinib 100 mg once daily, 50 mg twice daily, 140 mg once daily,
      or 70 mg twice daily. At 6 years, 188 (28%) of 670 patients remained on study
      treatment. Estimated 6-year protocol-defined progression-free survival (PFS)
      rates were 49%, 51%, 40%, and 47%, respectively, and estimated 6-year overall
      survival (OS) rates were 71%, 74%, 77%, and 70%, respectively (intent-to-treat
      population, including protocol-defined progression or death after
      discontinuation). Estimated 6-year rates of survival without transformation on
      study treatment were 76%, 80%, 83%, and 74%, respectively. Major molecular
      response was achieved in 43% (100 mg once daily) and 40% (all other arms) of
      patients by 6 years. Molecular and cytogenetic responses at 3 and 6 months were
      highly predictive of PFS and OS. Notably, estimated 6-year PFS rates based on
      <=1%, >1% to 10%, and >10% BCR-ABL transcripts at 3 months were 68%, 58%, and
      26%, respectively. Most adverse events occurred by 2 years. Imatinib-resistant/
      intolerant patients with CML-CP can experience long-term benefit with dasatinib
      therapy, particularly if achieving BCR-ABL <=10% at 3 months. This study was
      registered at ClinicalTrials.gov: NCT00123474.

PMID- 24569265
TI  - Parameter identification of river water quality models using a genetic algorithm.
AB  - For solving the multi-parameter identification problem of a river water quality
      model, analytical methods for solving a river water quality model and traditional
      optimization algorithms are very difficult to implement. A new parameter
      identification model based on a genetic algorithm (GA) coupled with finite
      difference method (FDM) was constructed for the determination of hydraulic and
      water quality parameters such as the longitudinal dispersion coefficient, the
      pollutant degradation coefficient, velocity, etc. In this model, GA is improved
      to promote convergence speed by adding the elite replacement operator after the
      mutation operator, and FDM is applied for unsteady flows. Moreover the influence
      of observation noise on identified parameters was discussed for the given model.
      The method was validated by two numerical cases (in steady and unsteady flows
      respectively) and one practical application. The computational results indicated
      that the model could give good identification precision results and showed good
      anti-noise abilities for water quality models when the noise level <=10%.

PMID- 24569264
TI  - Activation-induced cytidine deaminase is dispensable for virus-mediated liver and
      skin tumor development in mouse models.
AB  - Activation-induced cytidine deaminase (AID) not only promotes immune diversity by
      initiating somatic hypermutation and class switch recombination in immunoglobulin
      genes but also provokes genomic instability by introducing translocations and
      mutations into non-immunoglobulin genes. To test whether AID is essential for
      virus-induced tumor development, we used two transgenic tumor models: mice
      expressing hepatitis C virus (HCV) core proteins (HCV-Tg), driven by the
      hepatitis B virus promoter, and mice expressing human papillomavirus type 8
      proteins (HPV8-Tg), driven by the Keratin 14 promoter. Both strains were analyzed
      in the absence and presence of AID by crossing each with AID (-/-) mice. There
      was no difference in the liver tumor frequency between the HCV-Tg/AID (+/+) and
      HCV-Tg/AID (-/-) mice at 20 months of age although the AID (+/+) mice showed more
      severe histological findings and increased cytokine expression. Furthermore, a
      low level of AID transcript was detected in the HCV-Tg/AID (+/+) liver tissue
      that was not derived from hepatocytes themselves but from intra-hepatic immune
      cells. Although AID may not be the direct cause of HCV-induced oncogenesis, AID
      expressed in B cells, not in hepatocytes, may prolong steatosis and cause
      increased lymphocyte infiltration into HCV core protein-induced liver lesions.
      Similarly, there was no difference in the time course of skin tumor development
      between the HPV8-Tg/AID (-/-) and HPV8-Tg/AID (+/+) groups. In conclusion, AID
      does not appear to be required for tumor development in the two virus-induced
      tumor mouse models tested although AID expressed in infiltrating B cells may
      promote inflammatory reactions in HCV core protein-induced liver pathogenesis. 

PMID- 24569266
TI  - Bioflocculation behaviours of microbial communities in water treatment.
AB  - We studied the flocculation behaviours of microbial communities in 21 soil,
      wastewater and activated sludge samples to clarify the effects of culture medium
      types on flocculation ability and screening efficiency, and to analyze diverse
      functions and microbial compositions. The bioflocculants produced by 33% of the
      microbial communities had flocculating efficiencies higher than 90%. Six out of
      the eight microbial communities with efficiencies over 94% were screened from the
      culture medium using dibutyl phthalate (DBP) as the carbon source. BF-BCT, which
      was derived from the Chinese cabbage soil sample, had the highest flocculating
      efficiency (99.6%), species diversity and uniformity. Nine highly efficient
      strains were separated and purified from seven different microbial communities,
      indicating that flocculating microorganisms are widely distributed in ecosystems.
      The 16S rRNA gene testing shows that the eight bacterial and the one fungal
      strains are common soil microorganisms. The flocculating abilities of BB11
      (Sphingobacterium multivorum) and SE3 (Galactomyces geotrichum) have never been
      reported hitherto. Six strains, including the most flocculating-active TB13 and
      JB17, were screened from the culture medium using DBP as the sole carbon source.
      In particular, we compared the performance of culture media and analyzed
      analogous microbial communities with a Biolog automatic micro-analysis system for
      the first time.

PMID- 24569267
TI  - Fate of hydrocarbon pollutants in source and non-source control sustainable
      drainage systems.
AB  - Sustainable drainage (SuDs) is an established method for managing runoff from
      developments, and source control is part of accepted design philosophy. However,
      there are limited studies into the contribution source control makes to pollutant
      removal, especially for roads. This study examines organic pollutants, total
      petroleum hydrocarbons (TPH) and polycyclic aromatic hydrocarbons (PAHs), in
      paired source and non-source control full-scale SuDs systems. Sites were selected
      to cover local roads, trunk roads and housing developments, with a range of SuDs,
      including porous asphalt, swales, detention basins and ponds. Soil and water
      samples were taken bi-monthly over 12 months to assess pollutant loads. Results
      show first flush patterns in storm events for solids, but not for TPH. The
      patterns of removal for specific PAHs were also different, reflecting varying
      physico-chemical properties. The potential of trunk roads for pollution was
      illustrated by peak runoff for TPH of > 17,000 MUg/l. Overall there was no
      significant difference between pollutant loads from source and non-source control
      systems, but the dynamic nature of runoff means that longer-term data are
      required. The outcomes of this project will increase understanding of organic
      pollutants behaviour in SuDs. This will provide design guidance about the most
      appropriate systems for treating these pollutants.

PMID- 24569268
TI  - Monitoring benzotriazoles: a 1 year study on concentrations and removal
      efficiencies in three different wastewater treatment plants.
AB  - Benzotriazole (BTri), 4- and 5-tolyltriazole (4-TTri, 5-TTri) were monitored over
      1 year in three wastewater treatment plants (WWTPs) with a membrane bioreactor
      (MBR-MH) and two conventional activated sludge systems (CAS-E, CAS-M). The
      influent/effluent concentrations and treatment stages removal efficiencies were
      monitored. 5-TTri was removed best (mean removal 80%) in the WWTP mainly by
      biodegradation followed by BTri (mean removal 45%) and 4-TTri (mean removal 15%)
      that showed a significant lower elimination. High removal fluctuations for all
      three benzotriazoles occurred over the four seasons with lowest removal during
      winter. All three WWTPs constituted a point source for BTs in the aquatic
      environment as concentration measurements in the receiving rivers upstream and
      downstream of the WWTP proved. While MBR-MH and CAS-M significantly increased the
      downstream concentrations, CAS-E only slightly increased the downstream
      concentrations as the receiving river was already contaminated with
      benzotriazoles from hydropower. 5-TTri was detected in lowest concentrations due
      to its good removal compared to BTri and 4-TTri that contribute to high effluent
      concentrations with the potential to accumulate due to insufficient self
      purification. 

PMID- 24569269
TI  - Anaerobic ammonium oxidation in polyvinyl alcohol and sodium alginate immobilized
      biomass system: a potential tool to maintain anammox biomass in application.
AB  - Anaerobic ammonium oxidation (anammox) has been proved to be a promising nitrogen
      removal method for treating ammonium-rich wastewater. However, because of the low
      growth rate of anammox bacteria, maintenance of a sufficient amount of anammox
      biomass in reactor became a key factor in application. Gel immobilization is an
      efficient method to prevent biomass from being washed out and to promote hyper
      concentrated cultures. This study focused on a nitrogen removal process by
      anammox enrichment culture immobilized in polyvinyl alcohol and sodium alginate
      (PVA-SA) gel beads. The rapid startup of reactor demonstrated that gel entrapment
      was supposed to be a highly effective technique for immobilizing anammox
      bacteria. The anammox bacteria present in the enrichment were identified to be
      Jettenia-like species (>98%). Moreover, the effect of hydraulic retention time
      (HRT), pH, and temperature on immobilized anammox processes were investigated.
      The effect of pH and temperature on the anammox process was evidently weakened in
      PVA-SA immobilized gel beads, however, the effect of HRT on the anammox reaction
      was enhanced. Therefore, a stable operated reactor could be obtained in an
      anaerobic sequencing batch reactor, which proved gel immobilization was an
      excellent method to maintain the biomass in anammox reactor for application. 

PMID- 24569270
TI  - Green roof hydrologic performance and modeling: a review.
AB  - Green roofs reduce runoff from impervious surfaces in urban development. This
      paper reviews the technical literature on green roof hydrology. Laboratory
      experiments and field measurements have shown that green roofs can reduce
      stormwater runoff volume by 30 to 86%, reduce peak flow rate by 22 to 93% and
      delay the peak flow by 0 to 30 min and thereby decrease pollution, flooding and
      erosion during precipitation events. However, the effectiveness can vary
      substantially due to design characteristics making performance predictions
      difficult. Evaluation of the most recently published study findings indicates
      that the major factors affecting green roof hydrology are precipitation volume,
      precipitation dynamics, antecedent conditions, growth medium, plant species, and
      roof slope. This paper also evaluates the computer models commonly used to
      simulate hydrologic processes for green roofs, including stormwater management
      model, soil water atmosphere and plant, SWMS-2D, HYDRUS, and other models that
      are shown to be effective for predicting precipitation response and economic
      benefits. The review findings indicate that green roofs are effective for
      reduction of runoff volume and peak flow, and delay of peak flow, however, no
      tool or model is available to predict expected performance for any given
      anticipated system based on design parameters that directly affect green roof
      hydrology. 

PMID- 24569271
TI  - The impact of stormwater source-control strategies on the (low) flow regime of
      urban catchments.
AB  - Stormwater management strategies increasingly recognise the need to emulate the
      pre-development flow regime, in addition to reducing pollutant concentrations and
      loads. However, it is unclear whether current design approaches for stormwater
      source-control techniques are effective in restoring the whole flow regime, and
      in particular low flows, towards their pre-development levels. We therefore
      modelled and compared a range of source-control stormwater management strategies,
      including some specifically tailored towards enhancing baseflow processes. The
      strategies were assessed based on the total streamflow volume and three low flow
      metrics. Strategies based on harvesting tanks showed much greater volume
      reduction than those based on raingardens. Strategies based on a low flow rate
      release, aimed at mimicking natural baseflow, failed to completely restore the
      baseflow regime. We also found that the sensitivity of the low flow metrics to
      the proportion of catchment treated varied amongst metrics, illustrating the
      importance of metrics selection in the assessment of stormwater strategies. In
      practice, our results suggest that realistic scenarios using low flow release
      from source-control techniques may not be able to fully restore the low flow
      regime, at least for perennial streams. However, a combination of feasibly-sized
      tanks and raingardens is likely to restore the baseflow regime to a great extent,
      while also benefitting water quality through the retention and filtration
      processes.

PMID- 24569272
TI  - Denitrifying kinetics and nitrous oxide emission under different copper
      concentrations.
AB  - Denitrifying activities and nitrous oxide (N2O) emission during denitrification
      can be affected by copper concentrations. Different denitrifiers were acclimated
      in sequencing batch reactors with acetate or methanol as the electron donor and
      nitrate as the electron acceptor. The effect of copper concentrations on the
      denitrifying activity and N2O emission for the acclimated denitrifiers was
      examined in batch experiments. Denitrifying activities of the acclimated
      denitrifiers declined with increasing copper concentrations, and the copper
      concentration exhibited a higher effect on denitrifiers acclimated with acetate
      than those acclimated with methanol. Compared with the control without the
      addition of copper, at the copper concentration of 1 mg/L, the acetate
      utilization rate reduced by 89% for acetate-acclimated denitrifiers, while the
      methanol utilization rate only reduced by 15% for methanol-acclimated
      denitrifiers. Copper also had different effects on N2O emission during
      denitrification carried out by various types of denitrifiers. For the acetate
      acclimated denitrifiers, N2O emission initially increased and then decreased with
      increasing copper concentrations, while for the methanol-acclimated denitrifiers,
      N2O emission decreased with increasing copper concentrations. 

PMID- 24569273
TI  - Removal kinetic of Escherichia coli and enterococci in a laboratory pilot scale
      wastewater maturation pond.
AB  - During the last 15 years several authors studied the disinfection in waste
      stabilisation pond (WSP) and several empirical models were developed. There are
      huge differences between the models describing this process and there is really a
      need to improve the design of ponds for better disinfection. This paper addresses
      the Escherichia coli and enterococci disinfection in a laboratory pilot scale
      maturation pond (1.5 l) with light intensity (0, 12 and 25 W/m(2)) under
      controlled pH, temperature and dissolved oxygen (DO) conditions. The aim of this
      study is to improve modelling for a better design of disinfection in maturation
      ponds (MP) and to identify the key parameters influencing the process. It was
      found that kinetic coefficients K values for E. coli and enterococci are closely
      dependent on physicochemical parameters. K values increase with increasing pH, I,
      T and DO. E. coli disinfection depends closely on the pH and the DO and increases
      strongly when the pH is above 8.5. The enterococci disinfection depends
      essentially on DO. Two equations are suggested to calculate the kinetic
      coefficient K related to the environmental average state variables. 

PMID- 24569274
TI  - Granularity determination of activated sludge through on-line profiles by means
      of case-based reasoning.
AB  - Aerobic granulation from floccular sludge is difficult to detect in first stages
      with the naked eye. This work proposes a combination of multi-way principal
      components and case-based reasoning to predict the granulation state of a
      sequencing batch reactor, based solely on the on-line registered profiles of
      common sensors (i.e. pH, dissolved oxygen and oxidation-reduction potential). The
      methodology is able to discriminate between two active sludge granularities
      (floccular and granular). Two different scenarios are presented: one in which
      both granularities are present, and another scenario for which the granular state
      is not initially available. Analysis reported pH as the key variable in the
      transition between both states according to its variation, and that, in general,
      the granularity of the process can be correctly predicted at the end of the
      anaerobic phase. This methodology improves process monitoring capabilities during
      granulation and is an on-line alternative to a microscope analysis before the
      batch release. 

PMID- 24569275
TI  - Application of artificial neural network for modeling of phenol mineralization by
      photo-Fenton process using a multi-lamp reactor.
AB  - An artificial neural network (ANN) was implemented for modeling phenol
      mineralization in aqueous solution using the photo-Fenton process. The
      experiments were conducted in a photochemical multi-lamp reactor equipped with
      twelve fluorescent black light lamps (40 W each) irradiating UV light. A three
      layer neural network was optimized in order to model the behavior of the process.
      The concentrations of ferrous ions and hydrogen peroxide, and the reaction time
      were introduced as inputs of the network and the efficiency of phenol
      mineralization was expressed in terms of dissolved organic carbon (DOC) as an
      output. Both concentrations of Fe(2+) and H2O2 were shown to be significant
      parameters on the phenol mineralization process. The ANN model provided the best
      result through the application of six neurons in the hidden layer, resulting in a
      high determination coefficient. The ANN model was shown to be efficient in the
      simulation of phenol mineralization through the photo-Fenton process using a
      multi-lamp reactor. 

PMID- 24569276
TI  - Novel method for sludge blanket measurements.
AB  - The most widely used methods for sludge blanket measurements are based on
      acoustic or optic principles. In operation, both methods are expensive and often
      maintenance-intensive. Therefore a novel, reliable and simple method for sludge
      blanket measurement is proposed. It is based on the differential pressure
      measurement in the sludge zone compared with the differential pressure in the
      clear water zone, so that it is possible to measure the upper and the lower
      sludge level in a tank. Full-scale tests of this method were done in the
      secondary clarifier at the waste water treatment plant in Hecklingen, Germany.
      The result shows a good approximation of the manually measured sludge level. 

PMID- 24569277
TI  - Environmental assessment of different dewatering and drying methods on the basis
      of life cycle assessment.
AB  - Sewage sludge is an inevitable product of wastewater treatment in municipal
      wastewater plants and its amount has increased dramatically due to the growing
      number of sewage systems users. This sludge needs to be adequately treated in
      order to decrease its hazardous properties and any negative influence on the
      environment. In this paper, gate to gate analysis, on the basis of life cycle
      assessment (LCA), was carried out in order to compare the environmental impact of
      alternative ways of sludge processing employing a dewatering press and three
      different kinds of dryers - belt dryer, container dryer and batch dryer. SimaPro
      7.2 software and Ecoinvent 2.2 database were used to estimate the carbon
      footprint and energy balance of these processes. The main energy consumption in
      the scenarios analyzed is caused by the drying process. The solution based on
      application of the batch dryer allows a saving of 39.6% of energy compared with
      the most energy-consuming solution using a belt dryer. Sludge processing using
      belt and container dryers cause greater environmental burdens. 

PMID- 24569279
TI  - Performance of novel sludge-bed anaerobic membrane bioreactor (SB-AnMBR) treating
      prehydrolysis liquor.
AB  - The feasibility of a novel sludge-bed anaerobic membrane bioreactor (SB-AnMBR)
      configuration for treating a waste stream from a dissolving pulp production
      industry was evaluated. The waste stream, called prehydrolysis liquor (PHL), is
      generated after the wood chips are subjected to high temperature steam to remove
      unwanted hemicelluloses. The PHL with total chemical oxygen demand (COD) of
      approximately 100 g/L contained mainly sugars, furfural, lignin, and acetic acid.
      The SB-AnMBR was fed with the PHL at organic loading rates in a range of 0.8 to10
      kg-COD/(m(3).d). The COD removal efficiency of more than 85% and an average rate
      of methane production of 0.35 m(3)/(kg-COD.d) were observed at each loading rate.
      No detectable sugars or furfural were present in the treated effluent from SB
      AnMBR. Lignin removal varied from 60 to 90%. Flat-sheet membranes performed well
      with one fouling event during first 400 days of operation. 

PMID- 24569278
TI  - The water footprint of Milan.
AB  - This study quantifies the water footprint of consumption (WFcons) and production
      (WFprod) of Milan. The current WFcons amounts to 6,139 l/cap/d (a volume of 2.93
      km(3) annually), of which 52 l/cap/d (1%) is attributed to domestic water, 448
      l/cap/d (7%) to the consumption of industrial products and 5,639 l/cap/d (92%) to
      the consumption of agricultural products. The WFprod is 52 l/cap/d. Milan is thus
      a net virtual water importer, predominantly through the import of agricultural
      products. These are produced outside city borders, both in Italy and abroad. This
      shows the dependency of city dwellers on water resources from other river basins.
      In addition, the WFcons for a healthy diet (based on Mediterranean Food-Based
      Dietary Guidelines) and a vegetarian diet are analysed. The current Milanese diet
      consists of too much sugar, crop oils, meat, animal fats, milk and milk products
      and not enough cereals, rice, potatoes, vegetables and fruit. The latter two
      diets result in substantial WFcons reductions: -29% (to 4,339 l/cap/d) for a
      healthy diet and -41% (to 3,631 l/cap/d) for a vegetarian diet. Indeed, a lot of
      water could be saved by Milan citizens through a change in their diet. A
      sustainable city should account for its impacts beyond its borders.

PMID- 24569280
TI  - Improving products of anaerobic sludge digestion by microaeration.
AB  - Biogas, digested sludge and sludge liquor are the main products of anaerobic
      sludge digestion. Each of the products is influenced significantly by specific
      conditions of the digestion process. Therefore, any upgrade of the digestion
      technology must be considered with regard to quality changes in all products.
      Microaeration is one of the methods used for the improvement of biogas quality.
      Recently, microaeration has been proved to be a relatively simple and highly
      efficient biological method of sulfide removal in the anaerobic digestion of
      biosolids, but little attention has been paid to comparing the quality of
      digested sludge and sludge liquor in the anaerobic and microaerobic digestion and
      that is why this paper primarily deals with this area of research. The results of
      the long-term monitoring of digested sludge quality and sludge liquor quality in
      the anaerobic and microaerobic digesters suggest that products of both
      technologies are comparable. However, there are several parameters in which the
      'microaerobic' products have a significantly better quality such as: sulfide (68%
      lower) and soluble chemical oxygen demand (COD) (33% lower) concentrations in the
      sludge liquor and the lower foaming potential of the digested sludge. 

PMID- 24569281
TI  - Factor analysis and discriminant analysis of wastewater quality in
      Vidyaranyapuram sewage treatment plant, Mysore, India: a case study.
AB  - Wastewater treatment plant monitoring is an essential part of effective
      wastewater management. The analysis of eight physico-chemical parameters of
      untreated wastewater was carried out at Vidyaranyapuram sewage treatment plant,
      Mysore, India. Factor analysis (FA) was applied to the untreated wastewater data
      matrix, and pollution was found to be the most contributing factor, explaining
      22.31% of the total variance (chloride, biochemical oxygen demand, chemical
      oxygen demand and total dissolved solids). The second most contributing factor
      was found to be nitrification which explained 21.11% of the total variance (pH
      and nitrate), whereas the salinization factor contributed 16.98% of the total
      variance (total solids and total suspended solids). FA regression scores could
      not satisfactorily classify the data matrix with respect to the seasonal
      variations. Discriminant analysis (DA) was used to find the seasonal variations
      in the data matrix, and the standard mode DA explained 66.6% of total variance by
      grouping the cases with respect to seasons. 

PMID- 24569283
TI  - The effect of flow velocity on the distribution and composition of extracellular
      polymeric substances in biofilms and the detachment mechanism of biofilms.
AB  - Flume experiments were conducted to investigate the distribution and composition
      of extracellular polymeric substances (EPS) in biofilms and the detachment
      mechanism of biofilms grown under different flow velocity conditions. The results
      of biofilm growth kinetics showed that the growth trends were coincident with the
      logistic growth model. The growth kinetics parameters reached their maximum under
      intermediate velocity (IV) condition. Biofilms exhibited different profiles of
      EPS composition and distribution, depending on the flow conditions in which the
      biofilms were grown. The amounts of total polysaccharide and total protein in the
      thin biofilm (high velocity condition 2 - HV2) were both generally greater than
      those in the thick biofilm (IV). As compared to the heterogeneous distribution of
      EPS in the thick biofilms (IV), the EPS in the thin biofilms (HV2) exhibited more
      homogeneous distribution, and the bound EPS in the thin biofilms (HV2) were much
      greater than those in the thick biofilms (IV). From the detachment tests, an
      inverse relationship was observed between the proportion of detached biomass and
      the value of flow velocity during growth. Biofilms grown under higher velocities
      showed stronger cohesion than those grown under lower velocities. Therefore,
      water velocity during biofilm growth conditioned the distribution and composition
      of EPS, as well as its detachment characteristics under higher shear stress. 

PMID- 24569282
TI  - Ultrasound-assisted removal of tetracycline from aqueous solution by mesoporous
      alumina.
AB  - This work describes the removal of tetracycline (TC) from aqueous solution using
      a mesoporous alumina (meso-Al2O3) as adsorbent in the presence of ultrasonic
      irradiation. Adsorption of TC was investigated under various operating
      conditions, including pH, adsorbent dosage, ultrasound power, and initial TC
      concentration. The results showed that the rate of TC sorption was enhanced with
      the assistance of ultrasound. The TC removal increased with the increase in
      sorbent dosage, pH and ultrasound power, but decreased with the increase in
      initial TC concentration. The adsorption isotherm data were fitted properly with
      the Freundlich model under ultrasonic irradiation, and the adsorption process
      followed a pseudo-second-order kinetic model. 

PMID- 24569284
TI  - Adsorption performance and mechanism for removal of Cd(II) from aqueous solutions
      by D001 cation-exchange resin.
AB  - The adsorption and desorption properties of D001 resin for Cd(II) has been
      investigated. Batch studies were carried out with various pH, contact time,
      temperature and initial concentrations, and then column studies were conducted.
      The results showed that the optimal adsorption condition was at pH value of 3.0
      in HAc-NaAc medium. The resin exhibited a high Cd(II) uptake of 185.8 mg/g at 298
      K. The apparent activation energy Ea is 5.05 kJ/mol and the sorption
      thermodynamic parameters are DeltaH = 21.1 kJ/mol, DeltaS = 0.122 kJ/(mol K) and
      DeltaG298K = -15.3 kJ/mol, which indicated that the adsorption process was
      spontaneous and endothermic. Compared with the Freundlich isotherm, the sorption
      of Cd(II) obeys the Langmuir isotherm better. The Thomas model was delineated
      here to predict the breakthrough curves based on the experimental column study
      data. Furthermore, the resin could be regenerated through the desorption of the
      Cd(II) anions using 1 mol/L HCl solution and could be reused to adsorb again. The
      infrared spectroscopic technique was undertaken. Compared with other absorbents,
      D001 resin was relatively low cost and was effective in removing Cd(II) ions. 

PMID- 24569285
TI  - Ammonium reduction from piggery wastewater using immobilized ammonium-reducing
      bacteria with a full-scale sequencing batch reactor on farm.
AB  - This work aims to evaluate the efficiency of ammonium removal from piggery
      wastewater by an intermittent aeration (IA) sequencing batch reactor (SBR) with
      immobilized NH4(+)-reducing bacteria under mesophilic conditions. When a 20-L
      bench-scale SBR with 11% (v/v) of alginate beads containing NH4(+)-reducing
      bacteria was used, removal efficiency of NH4(+) was 63% after 240 h. When a full
      scale SBR system (available volume = 83 m(3)) with 0.1% (v/v) of alginate-coated
      light-expanded clay aggregates beads containing NH4(+)-reducing bacteria was
      used, removal efficiency of NH4(+) by the full-scale intermittent aeration SBR
      (IA-SBR) was significantly different from both traditional intermittent aeration
      SBR (T-SBR) and the continuous aeration SBR with AL beads containing NH4(+)
      reducing bacteria (P < 0.05). In summary, the IA-SBR with AL beads can
      significantly promote removal efficiency of NH4(+) on farm. 

PMID- 24569286
TI  - Nutrient-based ecological consideration of a temporary river catchment affected
      by a reservoir operation to facilitate efficient management.
AB  - The water quality status of the Kouris river in Cyprus was examined in order to
      fulfil the requirements for ecological quality as defined by the Water Framework
      Directive-2000/60/EC. Nitrate concentration (mean value) was increased in the
      Limnatis (2.8 mg L(-1)) tributary in comparison with the Kryos (2.1 mg L(-1)) and
      Kouris (1.0 mg L(-1)) tributaries depicting the influence of anthropogenic
      activities. The total maximum daily nutrients loads (TMDLs) based on the flow
      duration curves approach, showed that nutrients loads exceeded threshold values
      (33.3-75.6% in all hydrologic condition classes in the Kouris tributary, and 65
      78% in the Limnatis tributary) especially under low flow conditions. The TMDL
      graph is intended to guide the temporal schedule for chemical sampling in all
      hydrologic classes. Kouris reservoir is an oligotrophic system, strongly
      influenced by the river's flash-flood character but also by the implemented
      management practices. Kouris river outflow, which was reduced to one-tenth in the
      post dam period altered the wetland hydrologic network and contributed to the
      decrease of aquifer thickness. Continuous evaluation and update of the River
      Basin Management Plans will be the basis for the sustainable development of the
      Kouris basin. 

PMID- 24569287
TI  - Biological treatment of pharmaceutical wastewater from the antibiotics industry.
AB  - Pharmaceutical wastewater generated by an antibiotics (penicillin) company was
      treated by aerobic membrane bioreactors (MBRs) and sequencing batch reactors
      (SBRs). At a low organic loading rate of 0.22 kg-COD m(-3)d(-1), both types of
      reactors were capable of treating the wastewater such that the treated effluent
      met the discharge regulation except for the total dissolved solids. However, when
      the loading rate was increased to 2.92 kg-COD m(-3)d(-1), foaming issues resulted
      in unstable performance. Overall, the MBRs achieved better solid removal but the
      SBRs performed better in regards to the degradation of aromatic compounds, as
      determined by UV absorbance (UVA). Finally, ozonation was applied on two
      different streams and showed promise on the strong stream - that corresponds to
      the formulation effluent and contains most of the biorefractory compounds.
      Ozonation successfully reduced the UVA, lowered the pH and increased the
      biochemical oxygen demand : chemical oxygen demand (BOD5 : COD) ratio of the
      strong stream. However, it was less efficient on the effluent having undergone
      pre-treatment by a biofilter due to a lack of selectivity towards refractory
      compounds. 

PMID- 24569288
TI  - Comparison of the inspector and rating protocol uncertainty influence in the
      condition rating of sewers.
AB  - Wastewater drainage systems asset management decisions, in particular regarding
      rehabilitation interventions, are largely dependent on close-circuit television
      (CCTV) inspection results. However, the results of CCTV inspections are affected
      by several sources of uncertainty. Within the present communication, the
      inspector's uncertainty is quantified by comparing periodic inspection reports
      from three trunk sewers of a Portuguese sewer system. The inspections were
      carried out by the same experienced inspector using the same equipment.
      Therefore, the uncertainties from the lack of experience and the difference of
      the inspector and equipment were ruled out. The protocol uncertainty is also
      quantified comparing the results obtained with the Water Research Center (WRc)
      and the National Research Council of Canada (NRC) protocols condition ratings.
      Both operational and structural condition rating were analysed, but emphasis was
      given to the later since it dictates the repair and replacement interventions. 

PMID- 24569289
TI  - Recovery of water and acid from leach solutions using direct contact membrane
      distillation.
AB  - This paper describes for the first time the use of direct contact membrane
      distillation (DCMD) for acid and water recovery from a real leach solution
      generated by a hydrometallurgical plant. The leach solutions considered contained
      H2SO4 or HCl. In all tests the temperature of the feed solution was kept at 60 
      degrees C. The test work showed that fluxes were within the range of 18-33
      kg/m(2)/h and 15-35 kg/m(2)/h for the H2SO4 and HCl systems, respectively. In the
      H2SO4 leach system, the final concentration of free acid in the sample solution
      increased on the concentrate side of the DCMD system from 1.04 M up to 4.60 M.
      The sulfate separation efficiency was over 99.9% and overall water recovery
      exceeded 80%. In the HCl leach system, HCl vapour passed through the membrane
      from the feed side to the permeate. The concentration of HCl captured in the
      permeate was about 1.10 M leaving behind only 0.41 M in the feed from the initial
      concentration of 2.13 M. In all the experiments, salt rejection was >99.9%. DCMD
      is clearly viable for high recovery of high quality water and concentrated H2SO4
      from spent sulfuric acid leach solution where solvent extraction could then be
      applied to recover the sulfuric acid and metals. While HCl can be recovered for
      reuse using only DCMD. 

PMID- 24569290
TI  - Fate of organic pollutants in a pilot-scale membrane bioreactor-nanofiltration
      membrane system at high water yield in antibiotic wastewater treatment.
AB  - A double membrane system combining a membrane bioreactor (MBR) with a
      nanofiltration (NF) membrane at the pilot scale was tested to treat real
      antibiotic wastewater at a pharmaceutical company in Wuxi (China). The water
      yield of the pilot system reached over 92 +/- 5.6% through recycling the NF
      concentrate to the MBR tank. Results showed that the pilot scale system operated
      in good conditions throughout the entire experiment period and obtained excellent
      water quality in which the concentrations of chemical oxygen demand and total
      organic carbon were stable at 35 and 5.7 mg/L, respectively. The antibiotic
      removal rates of both spiramycin (SPM) and new spiramycin in wastewater were over
      95%. Organics analysis results showed that the main organics in the biological
      effluent were proteins, soluble microbial by-product-like, fulvic acid-like and
      humic-like substances. These organics could be perfectly rejected by the NF
      membrane. Most of the organics could be removed through recycling NF concentrate
      to the MBR tank and only a small part was discharged with NF concentrate and
      permeate. 

PMID- 24569291
TI  - Sonochemical degradation of chlorobenzene in the presence of additives.
AB  - The present work deals with establishing the pathway for the selection of
      additives for intensification of the sonolytic degradation of chlorobenzene. The
      degradation of chlorobenzene has been investigated in the presence of different
      additives such as CuO, TiO2, nano-TiO2 and NaCl. The reaction has been monitored
      in terms of the concentration of the parent pollutant as well as the extent of
      mineralization. The first-order kinetic rate constant for the removal of
      chlorobenzene has been evaluated for different loadings of additives. It has been
      observed that the extent of degradation and mineralization was maximum in the
      presence of nano-TiO2 and minimum in the presence of CuO. A three-step mechanism
      has been developed for the degradation of chlorobenzene based on the
      identification of intermediates. The removal of chloride from the benzene ring
      due to pyrolysis was the dominant mechanism with minimal contribution from the
      attack of hydroxyl radical present in the bulk of solution. The oxidation
      products also react subsequently with the hydroxyl radicals resulting in
      mineralization. The rate of mineralization has been quantified in terms of total
      organic carbon removal. The observed trends for the mineralization confirm that
      the extent of mineralization depends on the ease of generation of hydroxyl
      radicals. 

PMID- 24569292
TI  - Anaerobic digestion foaming in full-scale biogas plants: a survey on causes and
      solutions.
AB  - Anaerobic digestion foaming is a common operation problem in biogas plants with
      negative impacts on the biogas plants economy and environment. A survey of 16
      Danish full-scale biogas plants on foaming problems revealed that most of them
      had experienced foaming in their processes up to three times per year. Foaming
      incidents often lasted from one day to three weeks, causing 20-50% biogas
      production loss. One foaming case at Lemvig biogas plant has been investigated
      and the results indicated that the combination of feedstock composition and
      mixing pattern of the reactor was the main cause of foaming in this case.
      Moreover, no difference in bacterial communities between the foaming and non
      foaming reactors was observed, showing that filamentous bacteria were not the
      main reason for foaming in this case. 

PMID- 24569293
TI  - Growth of microalgal biomass on supernatant from biosolid dewatering.
AB  - The paper reports the results of an experiment to assess the feasibility of
      including a photobioreactor within the design of a wastewater treatment plant,
      growing microalgae on the centrate from anaerobic sludge dewatering. The growth
      of algal biomass would take advantage of the available nitrogen and provide a
      substrate for biogas production by anaerobic digestion. Tests were carried out by
      semi-continuously feeding a photobioreactor with a centrate-effluent blend and by
      increasing the fraction of centrate. The experimental results show that the
      centrate does not induce any toxicity and, on the contrary, can be well utilized
      by microalgae, whose average specific growth rate (MU), on centrate as such, was
      between 0.04 and 0.06 d(-1). The maximum biomass concentration in the
      photobioreactor effluent was 1.6 gSS/L at 10 days HRT (hydraulic retention time).
      Methane production tests led to biochemical methane production values of 335 +/-
      39, and 284 +/- 68 mL 0 degrees C, 1 atm CH4/g VS for the two tested samples, in
      agreement with literature values. Settling tests show that the settling capacity
      of microalgae, although satisfactory, could be effectively improved after mixing
      with activated sludge, confirming the potential to use the existing primary
      settler for microalgae thickening in order to feed microalgae for anaerobic
      digestion with primary/secondary sludge. 

PMID- 24569294
TI  - The semi-sewer river: hydraulic backwater effects and combined sewer overflow
      reverse flows in Central Brussels reduce deoxygenation impact further downstream.
AB  - In 2011 and 2012 the dissolved oxygen content in the low-discharge river Zenne
      was monitored continuously, every 5 minutes, downstream of Brussels city centre,
      making it possible to document the complex mechanisms by which combined sewer
      overflow (CSO) spills affect both the hydraulics and the oxygen balance of the
      hydrosystem. In addition to oxygen demand impacts, proportions of water volumes
      are such that the oxygen-devoid sewage water discharged from CSOs contributes
      significantly to the oxygen deficit observed in the river further downstream. It
      is shown that ensuing unexpected hydraulic behaviour, such as a full river-flow
      reversal, can explain the dual nature of oxygen sag following major CSO events.
      At times the semi-sewer river plays the role of an in-stream stormwater tank,
      effectively attenuating the environmental impacts of Brussels CSOs. 

PMID- 24569199
TI  - Guidelines for the prevention and treatment of opportunistic infections in HIV
      exposed and HIV-infected children: recommendations from the National Institutes
      of Health, Centers for Disease Control and Prevention, the HIV Medicine
      Association of the Infectious Diseases Society of America, the Pediatric
      Infectious Diseases Society, and the American Academy of Pediatrics.

PMID- 24569296
TI  - [Evaluation of hearing loss parameters in workers and its relationship with
      fasting blood glucose levels].
AB  - INTRODUCTION: Hearing loss due to noise is considered within the prevention plans
      of the most common occupational diseases. In addition to evaluation of working
      conditions, other personal factors increasing the risk of hypoacusis, such as
      diabetes, should be taken into account. OBJECTIVES: To explore hearing loss in
      the workplace and its relationship to impaired fasting baseline blood glucose
      levels. METHODS: An observational, cross-sectional study enrolling 1636 workers
      from service companies was conducted. Full audiometric evaluation was performed
      at different frequencies: high frequency (HF), early loss index (ELI), speech
      average loss (SAL), and monaural and binaural loss. Results were categorized by
      baseline blood glucose levels: G1 (<100mg/dl), G2 (100-125mg/dl), and G3
      (>125mg/dl). RESULTS: Based on both HF and ELI, 11% of workers had clear
      indication of deafness. Women with G3 levels showed significant differences in
      the results of HF and ELI indexes as compared to the G1 group (P=.038 and .046,
      respectively). A positive association was found between hearing loss and G3 blood
      glucose levels in HF (OR: .338; p=.002), ELI (OR: .407; p=.007), and the monaural
      test in the left ear (OR: 4.77*10-5; p=.006). CONCLUSIONS: Despite the
      methodological limitations of this study, there is evidence for an increased risk
      of high frequency hearing loss in workers with high baseline blood glucose
      levels.

PMID- 24569295
TI  - A novel membrane fusion protein family in Flaviviridae?
AB  - Enveloped viruses must fuse their lipid membrane to a cellular membrane to
      deliver their genome into the cytoplasm for replication. Viral envelope proteins
      catalyze this critical membrane fusion event. They fall into three distinct
      structural classes. In 2013, envelope proteins from a pestivirus and hepatitis C
      virus were found to have two distinct novel folds. This was unexpected because
      these viruses are in the same family as flaviviruses, which have class II fusion
      proteins. We propose that the membrane fusion machinery of the closely related
      pestiviruses and hepatitis C virus defines a new structural class. This and other
      recently identified structural relationships between viral fusion proteins shift
      the paradigm for how these proteins evolved. 

PMID- 24569297
TI  - Passive protection of mice pups through oral or intranasal immunization of dams
      with recombinant Lactobacillus casei vaccine against ETEC F41.
AB  - Mucosal immunization is advantageous over other routes of antigen delivery
      because it can induce both mucosal and systemic immune responses. In this study,
      we have developed fimbriae protein of enterotoxigenic Escherichia coli (ETEC) F41
      was stably expressed on the surface Lactobacillus casei 525. The method of
      expressing vaccine antigens in L. casei induces both systemic and mucosal
      immunity after oral or intranasal administration. We demonstrate that an oral or
      intranasal vaccine based on live recombinant L. casei 525 protects infant mice
      from ETEC F41 infection. This platform technology can be applied to design oral
      or intranasal vaccine delivery vehicles against several microbial pathogens. 

PMID- 24569298
TI  - Fosfomycin susceptibility of canine methicillin-resistant Staphylococcus
      pseudintermedius isolates.
AB  - The effectiveness of fosfomycin was examined across 31 methicillin-resistant
      Staphylococcus pseudintermedius (MRSP) strains by agar dilution. Prevalence of
      the fosfomycin-resistance determinant gene, fosB, was assessed by PCR analysis.
      Results found that 84% of isolates were fosfomycin-susceptible. Interestingly,
      87% of isolates possessed fosB, indicating no association between this putative
      staphylococci resistance gene and phenotypic resistance. Further evaluation of
      fosfomycin as a potential treatment of MRSP in dogs is warranted. 

PMID- 24569302
TI  - Final storage of radioactive cesium by pollucite hydrothermal synthesis.
AB  - The Fukushima nuclear accident has highlighted the importance of finding a better
      final storage method for radioactive cesium species. Cs is highly soluble in
      water, and can easily exchange with other alkali ions in zeolites or clays to
      form stable complexes. However, Cs(+) is released from Cs(+) complexes into water
      when surrounded by an excess of water. Pollucite may be the best final storage
      option for Cs(+), but its typical synthesis requires heating to about 1200 
      degrees C in air. Here, we show that the hydrothermal synthesis of pollucite can
      be completed at 300  degrees C in three hours from any zeolite or clay.
      Furthermore, our procedure does not require ion exchange before synthesis.
      Radioactive Cs is usually found in complexes with clays. At that time, this
      method only requires calcium hydroxide, water, and three hours of hydrothermal
      synthesis, so the process is both inexpensive and practical for large-scale
      application. Pollucite is an analog of analcime zeolite, and contains a channel
      system 2.8 A in diameter, which is formed by 6-oxygen rings. As the diameter of
      Cs(+) is 3.34 A and each Cs(+) exists independently within a separate portion of
      the channel, Cs(+) cannot exit the pollucite framework without breaking it.

PMID- 24569299
TI  - Time course of inflammation resolution in patients with frequent exacerbations of
      chronic obstructive pulmonary disease.
AB  - BACKGROUND: When exacerbation of chronic obstructive pulmonary disease (AECOPD)
      occurs frequently, patients have high levels of airway and systemic inflammation
      and a poor quality of life. This study compared the nature and course of systemic
      and airway inflammation during AECOPD between patients who experienced frequent
      exacerbations and those with non-frequent exacerbations. MATERIAL AND METHODS:
      Consecutive hospitalized patients with AECOPD were recruited and divided into 2
      groups according to the frequency of AECOPD they had experienced in the previous
      year. Frequent exacerbators (defined as 2 or more AECOPD in the previous year)
      and non-frequent exacerbators (defined as zero or 1 AECOPD in the previous year).
      Inflammatory (interleukin 6, interleukin 8, myeloperoxidase, and C-reactive
      protein) and clinical (dyspnea, COPD assessment test (CAT), and peak expiratory
      flow) indices were assessed on the day of admission before starting therapy, day
      7 of treatment, the day of planned discharge (day 10-14), and 8 weeks after
      discharge. RESULTS: We analyzed data from 135 patients; 78 (57.8%) were non
      frequent exacerbators and 57 (42.2%) were frequent exacerbators. In both groups,
      the inflammatory and clinical indices at day 7, the day of planned discharge (day
      10-14), and 8 weeks were significantly improved compared to those at admission.
      Frequent exacerbators had a smaller reduction in their inflammatory indices and
      CAT scores between exacerbation onset and all the other time points compared with
      infrequent exacerbators. CONCLUSIONS: Frequent exacerbators have a reduced
      response to treatment of AECOPD in terms of inflammatory indices and quality of
      life.

PMID- 24569301
TI  - Preoperative total cholesterol predicts postoperative outcomes after partial
      hepatectomy in patients with chronic hepatitis B- or C-related hepatocellular
      carcinoma.
AB  - BACKGROUND: Total cholesterol (TC) can reflect the degree of liver damage in
      patients with chronic hepatitis B or C; its role in evaluating liver functional
      reserve and predicting postoperative complications remains unknown. METHODS: The
      prospectively collected data of 996 consecutive patients with chronic hepatitis B
      or C undergoing partial hepatectomy for hepatocellular carcinoma in a tertiary
      institution were retrospectively reviewed. The relationship between preoperative
      TC and postoperative liver insufficiency, morbidity and mortality were analyzed.
      RESULTS: TC showed significant correlation with postoperative complications on
      receiver operating characteristic curves, with area under the curve of 0.81 (P <
      .001), 0.79 (P < .001), and 0.85 (P < .001) for postoperative liver
      insufficiency, morbidity, and mortality, respectively. Using the calculated
      cutoff at 2.80 mmol/L, Patients with low TC had worse preoperative liver
      functional reserve and suffered from more postoperative complications when
      compared with patients with normal TC (>=2.8 mmol/L). Multivariate analysis
      revealed that low preoperative TC was more powerful in predicting poor
      postoperative outcomes than Child-Pugh's classification, indocyanine green (ICG)
      retention test, and Mayo End-Stage Liver Disease (MELD) score. It was an
      independent risk factor for postoperative morbidity (odds ratio [OR], 4.87; P <
      .001) and mortality (OR, 14.60; P < .001). CONCLUSION: Among patients with
      chronic virus B or C hepatitis receiving partial hepatectomy, a low TC (<2.8
      mmol/L) predicted poor postoperative outcomes. It was better than Child-Pugh's
      classification, ICG, and MELD score in the prediction of postoperative
      complications, and was useful in the preoperative evaluation of liver functional
      reserve.

PMID- 24569300
TI  - An initial assessment of correlations between host- and virus-related factors
      affecting analogues antiviral therapy in HBV chronically infected patients.
AB  - BACKGROUND: Success in treating hepatitis B virus (HBV) infection with nucleoside
      analogues drugs is limited by the emergence of drug-resistant viral strains upon
      prolonged therapy. In addition to mutation patterns in the viral polymerase gene,
      host factors are assumed to contribute to failure of treatment in chronic HBV
      infections. The aim of this study was to analyze the correlation between efficacy
      of antiviral therapy and the prevalence of HBV pretreatment drug-resistant
      variants. We also analyzed the role of heterogeneity in the promoter region of
      the IL-10 on the HBV pol/s gene polymorphisms and efficacy of analogues-driven
      therapy. MATERIAL AND METHODS: HBV DNA was extracted from 54 serum samples from
      chronic hepatitis B (CHB) patients. Drug-resistance mutations were analyzed using
      MALDI-TOF mass spectrometry technology (MALDI-TOF MS) and Multi-temperature
      single-strand conformation polymorphism (MSSCP). IL-10 gene promoter region
      polymorphisms at positions -1082, -819, and -592 were determined in allele
      specific PCR reactions (AS-PCR). RESULTS: Drug-resistance mutations were detected
      in 74% of naive and 93% of experienced patients, but the effect of pre-existence
      of drug-resistant HBV variants on antiviral therapy was not statistically
      significant (p=0.86). The role of polymorphisms at positions -1082 (p=0.88), -819
      (p=0.26), and -592 (p=0.26) of IL-10 promoter region polymorphisms was excluded
      from the response-predicting factors. The main host factors predicting successful
      response to antiviral therapy were female sex (p=0.007) and young age (p=0.013).
      CONCLUSIONS: The presence of drug-resistant HBV variants in baseline is not a
      viral predictor of good response to nucleoside/nucleotide analogues therapy. Only
      low HBV viral load predicted positive response to antiviral therapy. The ideal
      candidate for antiviral therapy is an immunocompetent, young female with low HBV
      viral load and elevated ALT activity.

PMID- 24569303
TI  - Does dual diagnosis affect violence and moderate/superficial self-harm in heroin
      addiction at treatment entry?
AB  - OBJECTIVES: The presence of aggressive and self-harm behaviors is common in
      heroin-addicted patients, but these frequent co-occurrences have been poorly
      investigated. Given the fact that self-harm may be seen as both a clear addictive
      behavior, with its opiate theory, and as part of psychiatric illness, such as
      psychosis and bipolar spectrum disorders, in this study, we intend to investigate
      which of the 2 models is more consistent. METHODS: We compared dual diagnosis
      with the clinical features of 30 moderate/superficial self-harmed and 162 violent
      heroin-addicted patients who reported aggressive behavior in the month preceding
      their request to be treated. As control group, we selected 808 lifetime
      nonviolent heroin-addicted patients. RESULTS: The presence of a bipolar spectrum
      diagnosis proved to be the highest risk factor (B = 4.33; exp(B) = 76.52; 95%
      confidence interval for exp(B) = 35.69-164.04; P < 0.001) for the presence of
      aggressive behavior (chi2= 433.05; df = 5; P < 0.001). The highest risk factor
      for the presence of moderate/superficial self-harm (chi2 = 24.83; df = 2; P <
      0.001) was a dual diagnosis for chronic psychosis (beta = 1.46; exp(B) = 4.34);
      95% confidence interval for exp(B) = 1.11-16.98; P < 0.001). The relationships
      between aggressive and/or self-harm behaviors and the natural history of
      addiction in heroin-addicted patients seemed to be less consistent. CONCLUSIONS:
      Our data show a frequent co-occurrence of aggression and bipolar spectrum
      disorder in heroin-addicted patients, which is manifested as aggression directed
      toward others (violence). On the contrary, self-injurious behavior seems to be
      strongly correlated with psychotic disorders. Thus, aggressive behavior seems to
      be correlated, in heroin-addicted patients before entering treatment, with dual
      diagnosis rather than with a natural history of heroin addiction.

PMID- 24569305
TI  - Prospective validation of a risk prediction model for severe sepsis in children
      with cancer and high-risk febrile neutropenia.
AB  - BACKGROUND: We previously created a risk prediction model for severe sepsis not
      clinically apparent during the first 24 hours of hospitalization in children with
      high-risk febrile neutropenia (HRFN), which identified 3 variables, age >= 12
      years, serum C-reactive protein (CRP) >= 90 mg/L and interleukin-8 >= 300 pg/mL,
      evaluated at the time of admission and at 24 hours of hospitalization. The
      combination of these 3 variables identified a risk for severe sepsis ranging from
      8% to 73% with a relative risk of 3.15 (95% confidence interval: 1.1-9.06). The
      aim of this study was to validate prospectively our risk prediction model for
      severe sepsis in a new cohort of children with cancer and HRFN. METHODS:
      Predictors of severe sepsis identified in our previous model (age, CRP and
      interleukin-8) were evaluated at admission and at 24 hours of hospitalization in
      a new cohort of children with HRFN between April 2009 and July 2011. Diagnosis of
      severe sepsis, not clinically apparent during the first 24 hours of
      hospitalization, was made after discharge by a blind evaluator. RESULTS: A total
      of 447 HRFN episodes were studied, of which 76 (17%) had a diagnosis of severe
      sepsis. The combination of age >= 12 years, CRP >= 90 mg/L and interleukin-8 >=
      300 pg/mL at admission and/or at 24 hours in the new cohort identified a risk for
      severe sepsis ranging from 7% to 46% with an RR of 6.7 (95% CI: 2.3-19.5).
      CONCLUSIONS: We validated a risk prediction model for severe sepsis applicable to
      children with HRFN episodes within the first 24 hours of admission. We propose to
      incorporate this model in the initial patient assessment to offer a more
      selective management for children at risk for severe sepsis.

PMID- 24569304
TI  - Executive summary: 2013 update of the guidelines for the prevention and treatment
      of opportunistic infections in HIV-exposed and HIV-infected children.

PMID- 24569306
TI  - Helicobacter pylori Infection in European children with gastro-duodenal ulcers
      and erosions.
AB  - BACKGROUND: To analyze risk factors associated with gastro-duodenal ulcers and
      erosions in children. METHODS: Open, prospective, multicenter, case-control study
      carried out in 11 European countries in patients with gastric or duodenal
      ulcers/erosions and 2 age-matched controls each. Possible risk factors were
      recorded. Logistic regression models were performed with adjustment for centers
      and age groups. RESULTS: Seven-hundred thirty-two patients (244 cases, 153 with
      erosions only and 91 with ulcers, and 488 controls) were recruited. Children
      receiving antimicrobials or acid suppressive drugs before endoscopy were excluded
      (202 cases/390 controls remained for risk factor analysis). Helicobacter pylori
      was detected more frequently in cases than controls but only in 32.0% versus
      20.1% in controls (P = 0.001). Independent exposure factors for gastric ulcers
      were male gender (P = 0.001), chronic neurologic disease (P = 0.015), chronic
      renal disease (P < 0.001) and nonsteroidal anti-inflammatory drug consumption (P
      = 0.035). Exposure factors for duodenal ulcers were H. pylori infection (P <
      0.001) and steroid consumption (P = 0.031). Chronic renal disease was the only
      independent factor associated with gastric erosions (P = 0.026), those associated
      with duodenal erosions being H. pylori infection (P = 0.023), active smoking (P =
      0.006) and chronic arthritis (P = 0.008). No risk factor was identified in 97/202
      (48.0%) cases. CONCLUSIONS: H. pylori remains a risk factor for duodenal, but not
      for gastric lesions in children in countries with low prevalence of infection. No
      risk factor could be identified in half of the children with gastro-duodenal
      ulcers/erosions.

PMID- 24569307
TI  - Mycobacterium szulgai chronic multifocal osteomyelitis in an adolescent with
      inherited STAT1 deficiency.
AB  - We report a 17-year-old patient with inherited STAT1 deficiency, who was
      diagnosed with Mycobacterium szulgai chronic multifocal osteomyelitis and
      responded well to the therapy with ethambutol, rifampicin and azithromycin. Seven
      other reported cases of M. szulgai osteomyelitis are reviewed. This is the first
      description of M. szulgai osteomyelitis in an adolescent with a primary
      immunodeficiency. 

PMID- 24569308
TI  - Impact of rotavirus vaccine on childhood diarrheal hospitalization after
      introduction into the South African public immunization program.
AB  - BACKGROUND: Oral rotavirus vaccine was introduced into the South African routine
      immunization program in August 2009 administered at 6 and 14 weeks with no catch
      up. We described the change in rotavirus-associated diarrheal hospitalizations
      among children <5 years at 3 sentinel sites from 2009 through 2011. METHODS:
      During 2009 through 2011, we compared the proportion of enrolled children aged <5
      years hospitalized with acute gastroenteritis and testing rotavirus positive. We
      used hospital data to determine the change in diarrhea hospitalizations and
      estimated total numbers of rotavirus hospitalizations by adjusting for
      nonenrolled patients. Stool samples were tested for rotavirus using enzyme
      immunoassay. RESULTS: In 2009 (May-December), 46% (404/883) of samples among
      children <5 years tested rotavirus positive, decreasing to 33% (192/580) (P <
      0.001) in 2010 and 29% (113/396) (P < 0.001) in 2011. Compared with May-December
      2009, total diarrhea hospitalizations among children aged <5 years was one-third
      lower in May-December of 2010 and 2011. Among infants, adjusted rotavirus
      hospitalizations were 61% (n = 267) and 69% (n = 214) lower, respectively, in
      2010 and 2011 when compared with 2009 (n = 689), and 45 and 50 percentage points
      greater than the reduction in rotavirus-negative cases. Among children <5 years,
      rotavirus hospitalizations were 54% and 58% lower in 2010 and 2011, compared with
      2009 (40 and 44 percentage points greater than reduction in rotavirus-negative
      cases). Rotavirus reductions occurred in rural and urban settings. CONCLUSION:
      Using published estimates of rotavirus hospitalization burden, we estimate that
      at least 13,000 to 20,000 hospitalizations in children <2 years were prevented in
      the 2 years after rotavirus vaccine introduction.

PMID- 24569309
TI  - Influenza vaccination given at least 2 weeks before delivery to pregnant women
      facilitates transmission of seroprotective influenza-specific antibodies to the
      newborn.
AB  - BACKGROUND: Pregnant women and infants are at higher risk of complications
      secondary to influenza infection. Immunization during pregnancy facilitates
      protection of the neonates through passive transfer of maternal antibodies.
      METHODS: This was a cross-sectional study performed during the post-H1N1 pandemic
      winter season of 2010/2011 in Geneva, Switzerland. We measured antibody titers
      against the seasonal influenza A H1N1, H3N2 and B 2010/2011 strains by
      hemagglutination inhibition in the umbilical cord blood of newborns born to
      vaccinated and nonvaccinated mothers. Seroprotection was defined as a
      hemagglutination inhibition titer >= 40. RESULTS: A total of 188 women were
      enrolled, 101 of whom had been vaccinated with a nonadjuvanted influenza vaccine
      (all during the second or third trimester) and the other 87 had not. Among
      newborns of vaccinated women, 84-86% showed seroprotective levels depending on
      the strain. In comparison, seroprotection rates were significantly lower in
      babies of nonvaccinated women (29-33%, P < 0.001). Adjusting for various
      confounding factors and applying multivariate regression analysis, vaccination
      during pregnancy >= 2 weeks before delivery increased geometric mean titers in
      umbilical cord blood 5-17 times and seroprotection rates 5.8-34.4 times,
      depending on the strain and the interval between vaccination and delivery.
      Vaccinating pregnant women only 2-4 weeks before delivery was still more
      effective than no vaccination at all (geometric mean titers increased 6.8-11.1
      times and seroprotection rates increased 5.8-34.4 times compared with
      nonvaccinated women). CONCLUSIONS: Influenza vaccination at any time during the
      second and third trimester of pregnancy, but at least 15 days before delivery,
      confers seroprotection to many neonates.

PMID- 24569310
TI  - Performance of adjunctive therapy in bacterial meningitis depends on
      circumstances.

PMID- 24569311
TI  - Drug reaction with eosinophilia and systemic symptoms syndrome associated with
      antituberculosis medications.
AB  - Drug reaction with eosinophilia and systemic symptoms is a potentially life
      threatening syndrome of medication hypersensitivity associated with a wide
      variety of triggers. Diagnosis can be challenging, as clinical features suggest
      other conditions. We describe a 12-year-old boy with typical drug reaction with
      eosinophilia and systemic symptoms syndrome after antituberculosis therapy. 

PMID- 24569313
TI  - Molecular epidemiology in neonatal pasteurellosis.

PMID- 24569314
TI  - Interpretation of real-time PCR diagnosing fecal viruses in children: a
      prospective case-control study.

PMID- 24569312
TI  - Immunogenicity of Haemophilus influenzae type b protein conjugate vaccines in
      very low birth weight infants.

PMID- 24569315
TI  - Lower vancomycin serum trough concentrations might not be the answer.

PMID- 24569316
TI  - Reply: To PMID 23652479.

PMID- 24569317
TI  - Health needs of refugee children younger than 5 years arriving in New Zealand.
AB  - BACKGROUND: New Zealand accepts 750 refugees annually who enter via the Mangere
      Refugee Resettlement Centre. AIMS: To evaluate the health needs of refugee
      children less than 5 years of age. METHODS: Retrospective audit on the outcomes
      of health screening and referrals in children less than 5 years of age at the
      Mangere Refugee Resettlement Centre between 2007 and 2011. RESULTS: Of the 343
      children, the most common infectious diseases were latent tuberculosis (15%) and
      parasitic infections (15%). In those older than 1 year old who had rubella and
      measles serology information, immunity was found in 50% and 59%, respectively.
      Hepatitis B immunity was found in 68%. Complete vaccination certificates were
      available for 66% on arrival to New Zealand. Vaccinations were administered to
      73% while at the Mangere Refugee Resettlement Centre. Iron deficiency and vitamin
      D deficiency were the main noninfectious diseases found and were present in 33%
      and 12%, respectively. The total requiring referral for further medical
      assessment or support was 58% with 19% requiring referral to more than one
      service. CONCLUSIONS: Screening identified health needs in otherwise asymptomatic
      newly arriving refugee children. A proportion of children required access to
      multiple specialized medical services and may benefit from a comprehensive
      pediatric service.

PMID- 24569318
TI  - [Presentations and management of adrenal hypertension].
AB  - The frequency of the diagnosed causes of secondary hypertension is only known
      from hospital-based records, which probably overestimate the true prevalence.
      Excluding oral contraceptive users and cases with renal failure, their overall
      frequency was estimated at 1 percent in the eighties, 5 percent in the nineties,
      and 9 percent in recent years. This increase in frequency was mostly due to an
      increased number of diagnosed cases of endocrine hypertension. The diagnosis of
      endocrine hypertension is not synonymous with the diagnosis of a surgically
      correctable form of hypertension. Indeed, hypertension is surgically curable in a
      minority of patients, mostly in patients with aldosterone-secreting adenomas or
      with pheochromocytomas or functional paragangliomas. The presentation, screening,
      diagnosis and therapeutic management of endocrine hypertension are discussed in
      the present issue. 

PMID- 24569320
TI  - Potential climate engineering effectiveness and side effects during a high carbon
      dioxide-emission scenario.
AB  - The realization that mitigation efforts to reduce carbon dioxide emissions have,
      until now, been relatively ineffective has led to an increasing interest in
      climate engineering as a possible means of preventing the potentially
      catastrophic consequences of climate change. While many studies have addressed
      the potential effectiveness of individual methods there have been few attempts to
      compare them. Here we use an Earth system model to compare the effectiveness and
      side effects of afforestation, artificial ocean upwelling, ocean iron
      fertilization, ocean alkalinization and solar radiation management during a high
      carbon dioxide-emission scenario. We find that even when applied continuously and
      at scales as large as currently deemed possible, all methods are, individually,
      either relatively ineffective with limited (<8%) warming reductions, or they have
      potentially severe side effects and cannot be stopped without causing rapid
      climate change. Our simulations suggest that the potential for these types of
      climate engineering to make up for failed mitigation may be very limited. 

PMID- 24569319
TI  - Temporal difference error prediction signal dysregulation in cocaine dependence.
AB  - Cocaine dependence impacts drug-related, dopamine-dependent reward processing,
      yet its influence on non-drug reward processing is unclear. Here, we investigated
      cocaine-mediated effects on reward learning using a natural food reinforcer.
      Cocaine-dependent subjects (N = 14) and healthy controls (N = 14) learned to
      associate a visual cue with a juice reward. In subsequent functional imaging
      sessions they were exposed to trials where juice was received as learned,
      withheld (negative temporal difference error (NTDE)), or received unexpectedly
      (positive temporal difference error (PTDE)). Subjects were scanned twice in
      sessions that were identical, except that cocaine-dependent participants received
      cocaine or saline 10 min before task onset. In the insula, precentral and
      postcentral gyri NTDE signals were greater, and PTDE-related function was reduced
      in cocaine-dependent subjects. Compared with healthy controls, in the cocaine
      dependent group PTDE signals were also reduced in medial frontal gyrus and reward
      related function, irrespective of predictability, was reduced in the putamen.
      Group differences in error-related activity were predicted by the time as last
      self-administered cocaine use, but TDE function was not influenced by acute
      cocaine. Thus, cocaine dependence seems to engender increased responsiveness to
      unexpected negative outcomes and reduced sensitivity to positive events in
      dopaminergic reward regions. Although it remains to be established if these
      effects are a consequence of or antecedent to cocaine dependence, they likely
      have implications for the high-cocaine use recidivism rates by contributing to
      the drive to consume cocaine, perhaps via influence on dopamine-related reward
      computations. The fact that these effects do not acquiesce to acute cocaine
      administration might factor in binge-related escalated consumption.

PMID- 24569321
TI  - Acute renal dysfunction: time from coronary angiography to cardiac surgery.
AB  - BACKGROUND: The incidence of acute renal dysfunction has not changed much over
      the years, despite improvements in perioperative care. Our objectives were to
      evaluate the impact of timing of cardiac surgery after coronary angiography on
      acute renal dysfunction, to identify risk factors associated with development of
      acute renal dysfunction, and to measure the association between acute renal
      dysfunction and mortality. PATIENTS AND METHODS: The patients were divided into 3
      groups: group A (cardiac surgery 0-3 days after angiography), group B (surgery 4
      6 days after angiography), and group C (surgery > 6 days after angiography).
      Endpoints were acute renal dysfunction, defined as serum creatinine > 25% of
      baseline on the 3rd postoperative day, and mortality. RESULTS: In 749 patients,
      the incidence of acute renal dysfunction was 15%; 5% required dialysis.
      Hypertension, congestive heart failure, chronic obstructive pulmonary disease,
      ejection fraction < 40%, prolonged cardiopulmonary bypass time, intraaortic
      balloon pump use, and urgent surgery were risk factors for acute renal
      dysfunction after cardiac surgery. Patients in group C had a lower risk of acute
      renal dysfunction. CONCLUSION: Acute renal dysfunction has a definite
      relationship with the time period between angiography and cardiac surgery. The
      causative factors for this condition are multiple and also show a consistent
      association with mortality.

PMID- 24569322
TI  - Evaluation of myocardial fat deposition by multislice computed tomography.
AB  - AIM: To investigate correlations between myocardial fat deposition of unknown
      etiology and myocardial infarction, coronary artery stenosis, time after the
      infarction, aneurysmatic dilatation of arteries, and stenting or bypass
      operation. PATIENTS AND METHODS: We evaluated coronary computed tomography
      angiographies of 266 patients presenting with history of myocardial infarction or
      having risk factors for coronary artery disease, analyzed the characteristics of
      myocardial fat, and compared the clinical parameters of patients with and without
      myocardial fat. RESULTS: 34 of the 266 patients had myocardial fat deposits. Of
      the 34 with myocardial fat, 47% had a history of myocardial infarction.
      Myocardial fat occurrence after myocardial infarction was statistically
      significant. Myocardial fat was more frequently associated with longer time after
      infarction and fewer coronary arteries involved, but without statistical
      significance. A bypass operation and myocardial fat deposition correlated with
      aneurysmatic dilatation of the coronary arteries and myocardial fat deposition
      within the area supplied by this artery. CONCLUSION: Myocardial fat was detected
      in 34% of patients with myocardial infarction. Myocardial fat was significantly
      more frequent in patients who underwent a bypass operation and those who had
      aneurysmatic dilatation of the coronary arteries. The frequency of myocardial fat
      deposition increased with the involvement of fewer coronary arteries and longer
      time after infarction.

PMID- 24569323
TI  - Bilateral internal thoracic artery grafting in insulin-treated diabetes.
AB  - BACKGROUND: We sought to assess the risk and late outcome of bilateral internal
      thoracic artery grafting in eligible insulin-treated diabetic subsets. METHODS:
      147 insulin-treated diabetic patients undergoing arterial revascularization were
      grouped as: skeletonized bilateral internal thoracic artery (n = 83) or internal
      thoracic artery-radial artery (n = 64). Chronic lung disease or overweight and
      female constituted exclusion criteria for bilateral internal thoracic artery
      grafts. RESULTS: Patients who had bilateral internal thoracic artery grafts were
      younger and comprised fewer females. Left-sided bilateral internal thoracic
      artery configurations were predominantly applied. Despite mean hemoglobin A1c of
      8.0% +/- 1% (range, 7%-13.5%) respective rates of deep sternal infection in
      bilateral internal thoracic artery and radial artery patients were 1.2% and 0%;
      superficial wound infection occurred in 3.1% and 3.6%, respectively. One
      sternoplasty was performed. Bilateral internal thoracic artery grafting did not
      correlate with sternal complications (odds ratio = 2.24, 95%CI: 0.56-8.95, p =
      0.256). Of the radial artery conduits, 98% were adequate, and procurement-site
      complications occurred in 3.1%. Follow-up was 2-58 months (median, 25 months).
      Five-year survival was comparable in the 2 groups (p = 0.360). Bilateral internal
      thoracic artery grafting did not reduce late major adverse cardiac events (p =
      0.729) or late mortality (p = 0.384). CONCLUSIONS: Skeletonized bilateral
      internal thoracic artery grafts can be used with acceptable risk in a substantial
      portion of insulin-treated diabetic patients, so it should not be automatically
      denied, but the choice of such grafts is not associated with midterm cardiac
      benefits.

PMID- 24569324
TI  - Low dose tranexamic acid effect on post-coronary artery bypass grafting bleeding.
AB  - OBJECTIVE: This study investigated the effects of low-dose tranexamic acid on
      post-coronary artery bypass surgery bleeding. BACKGROUND: Diffuse microvascular
      bleeding is still a common problem after cardiac procedures. This study was
      designed to evaluate the hemostatic effects of low-dose tranexamic acid in on
      pump coronary artery bypass graft surgery. METHODS: In this prospective
      randomized placebo-controlled study, 150 patients who were candidates for
      coronary artery bypass were enrolled and randomly assigned to 1 of 2 groups
      (tranexamic acid or placebo). Total drainage volume and the need for transfusion
      as well as surgical complications were recorded and compared in the 2 groups.
      RESULTS: There was significantly less mediastinal chest tube drainage up to 48 h
      in the tranexamic acid group (432 +/- 210 mL) compared to the placebo group (649
      +/- 235 mL, p = 0.006). In the placebo group, 43 (58%) patients were given
      allogeneic blood during hospital stay compared to 22 (25%) in the tranexamic acid
      group (p < 0.001). No significant difference in postoperative complications was
      seen. CONCLUSION: The use of low-dose tranexamic acid can significantly reduce
      blood loss and need for transfusion, with no increase in complications.

PMID- 24569325
TI  - Congenital heart surgery outcome analysis: Indian experience.
AB  - BACKGROUND: The study aimed to analyze the outcome of congenital heart surgery in
      a subset of Indian patients, using the Aristotle Basic Complexity score, the Risk
      Adjustment for Congenital Heart Surgery categories, and the Society of Thoracic
      Surgeons and European Association for Cardiothoracic Surgery mortality
      categories. PATIENTS AND METHODS: 1312 patients <18 years of age undergoing
      congenital heart surgery were assigned the 3 scores and studied for outcome
      indices of difficulty (cardiopulmonary bypass time or duration of surgery >120
      min), morbidity (intensive care unit stay >7 days), and mortality. RESULTS: The
      overall mortality was 6.85%, with mean a Aristotle Basic Complexity score, Risk
      Adjustment for Congenital Heart Surgery category, and Society of Thoracic
      Surgeons and European Association for Cardiothoracic Surgery mortality category
      of 7.17 +/- 2.04, 2.28 +/- 0.78, and 2.24 +/- 1.06, respectively. The mortality
      predictive capacity of the Risk Adjustment for Congenital Heart Surgery category
      (c = 0.76) was similar to that of the Society of Thoracic Surgeons and European
      Association for Cardiothoracic Surgery mortality category (c = 0.75); both were
      better compared to the Aristotle Basic Complexity score (c = 0.66). The Risk
      Adjustment for Congenital Heart Surgery category and Aristotle Basic Complexity
      score correlated with morbidity and difficulty outcomes. CONCLUSION: The study
      shows that the Aristotle Basic Complexity score, the Risk Adjustment for
      Congenital Heart Surgery category, and the Society of Thoracic Surgeons and
      European Association for Cardiothoracic Surgery mortality category are tools of
      case mix stratification to analyze congenital heart surgery outcomes in a subset
      of the Indian population.

PMID- 24569326
TI  - Symmetrical excessive pectus excavatum in children.
AB  - OBJECTIVES: The indications for repair of pectus excavatum are controversial. We
      present our surgical results in children with severe pectus excavatum. METHODS:
      27 children aged 6-15-years were included in the study. Pulmonary function tests
      and chest measurements were performed pre- and postoperatively. Deformed
      cartilages were resected subperichondrially, and a Kirchner wire was used to
      support the chest cage; it was removed 5 days after the operation. Fourteen
      children with restricted pulmonary function were considered to have excessive
      pectus excavatum. RESULTS: 3 patients had asthma-like symptoms that resolved
      postoperatively. None suffered chest pain postoperatively. Postoperative hospital
      stay was 7.1 days. Only minor complications occurred postoperatively. The mean
      pectus severity index was 0.27 +/- 0.2 preoperatively and 0.41 +/- 0.1
      postoperatively (p < 0.05). For children with restricted pulmonary function, it
      was 0.17 +/- 0.3 preoperatively and 0.38 +/- 0.2 postoperatively (p < 0.05). Mean
      percentage of predicted forced expiratory volume in 1 s changed significantly
      from 79.2% +/- 17.8% preoperatively to 83.6% +/- 12.2% by the 3rd postoperative
      month. For children with a pectus severity index <0.2, it changed from 68.5% +/-
      13.2% preoperatively to 82.3% +/- 13.4%. Pulmonary restriction correlated with a
      worse pectus severity index (r = 0.8). After 6 and 13 months, a minor decrease in
      pulmonary function was noted. Significant increases in right and left ventricular
      function occurred in cases of severe deformity. CONCLUSIONS: Surgery is
      recommended not only for cosmetic reasons but also to increase cardiorespiratory
      functional capacity and alleviate symptoms. Kirchner wires can be used safely.

PMID- 24569327
TI  - Botulinum toxin for prevention of delayed gastric emptying after esophagectomy.
AB  - BACKGROUND: Esophageal cancer is among the most common gastrointestinal cancers
      for which the main treatment is surgery. This study was undertaken to analyze the
      results of Botox injection in preventing gastric stasis in these patients.
      PATIENTS AND METHODS: 60 patients with esophageal cancer in the middle and lower
      third parts were included in our study between 2010 and 2011, and were randomly
      divided into two groups. In group A, 30 patients underwent pyloroplasty, and in
      group B, injection of botulinum toxin into the pyloric sphincter muscle was used
      in 30 patients. RESULTS: The mean age of these patients was 61 +/- 10.7 years and
      the male/female ratio was 33:27. Isotope scans 3 weeks after surgery showed that
      5 patients in group A and 3 in group B had delayed gastric emptying; there was no
      significant difference between the 2 groups, and the success rate of Botox
      injection was 90%. CONCLUSION: Considering the fact that there was no significant
      difference between pyloroplasty and Botox injection on gastric emptying after
      surgery, and given the need to use less-aggressive techniques and facilitate
      greater use of endoscopic methods, botulinum toxin injection may be used instead
      of pyloroplasty as a simple, effective, and complication-free method to prevent
      delayed gastric emptying.

PMID- 24569328
TI  - Validation of 7th TNM staging system for lung cancer, based on surgical outcomes.
AB  - BACKGROUND: Validation of the clinical classification for lung cancer of the 7th
      edition of the TNM staging system among surgical cases has not been reported
      previously. METHODS: Data of 489 males and 246 females, with a mean age of 67.6
      years, who underwent surgical resection for non-small-cell lung cancer were
      analyzed retrospectively. RESULTS: The 5-year survival rate of these patients was
      72.2% for clinical stage IA (n = 365), 58.4% for IB (n = 158), 51.2% for IIA (n =
      77), 49.1% for IIB (n = 42), 36.8% for IIIA (n = 86), 80% for IIIB (n = 5) and
      50% for IV (n = 2). The 5-year survival rate of patients was 100% for
      pathological stage 0 (n = 2), 86.1% for IA (n = 216), 73.8% for IB (n = 173),
      46.1% for IIA (n = 97), 47.2% for IIB (n = 69), 33.3% for IIIA (n = 155), 33.3%
      for IIIB (n = 3) and 30.9% for IV (n = 20). Prognostic factors included female
      sex and 70 years of age or younger, as well as adenocarcinoma histology.
      CONCLUSIONS: Deterioration in patient survival was indicated with the exception
      of stages IIIB and IV, each of which included only a small number of patients.
      Our study validated the current TNM staging system in surgical cases with regard
      to both clinical and pathological classifications.

PMID- 24569329
TI  - Complete video-assisted thoracoscopic surgery for lung cancer in 400 patients.
AB  - BACKGROUND: We report the results of complete video-assisted thoracoscopic
      surgery for treatment of primary non-small cell lung cancer, which was performed
      completely through the monitor in 400 consecutive patients. PATIENTS AND METHODS:
      Between September 25, 2002 and August 25, 2011, a retrospective database of 400
      consecutive patients who underwent complete video-assisted thoracoscopic surgery
      for treatment of primary non-small cell lung cancer was reviewed. Demographic,
      histopathologic, preoperative, perioperative, postoperative, and outcome
      variables were assessed using standard descriptive statistics and Kaplan-Meier
      survival analyses. RESULTS: Operating time was 258.13 +/- 62.53 min, volume of
      blood loss was 253.21 +/- 206.66 mL, duration of drainage was 3.6 +/- 3.2 days,
      volume of drainage was 708.1 +/- 522.8 mL, the postoperative respiratory
      complication rate was 14.8%, the reoperation rate was 1.3%, and operative
      mortality was 1.0%. The 5-year postsurgical survival rates for pathologic stages
      I, II, and III were 93.9%, 62.0%, and 61.6%, respectively; the 3-year
      postsurgical survival rate for pathologic stage IV was 40.0% CONCLUSIONS:
      Complete video-assisted thoracoscopic surgery for treatment of primary non-small
      cell lung cancer is associated with safety and acceptable postoperative
      complication rates, operative mortality rates, and survival rates.

PMID- 24569330
TI  - Vacuum-assisted closure system in treatment of postoperative mediastinitis.
AB  - OBJECTIVES: Post-cardiac surgery mediastinitis is a serious complication with
      high morbidity and high financial costs. Using a vacuum-assisted closure system
      is the established line of treatment for mediastinitis, which improves outcome,
      especially in the high-risk group of patients. METHODS: From January 2007 to
      April 2011, a retrospective study was carried out to evaluate the outcome of
      vacuum-assisted closure in the treatment of postoperative mediastinitis. RESULTS:
      There were 34 patients; 27 were male and 7 female. Mean time from infection to
      vacuum-assisted closure was 3.34 +/- 1.10 days. The duration of vacuum-assisted
      closure was 6.51 +/- 1.85 days (3-9 days). The mean amount of discharge was
      759.60 +/- 175.28 mL (range, 354-990 mL). Of the 34 patients, 21 (61.76%) had
      direct surgical wound closure and 13 (41.16%) had re-wiring. Two patients had
      bilateral pectoral flaps. One patient had chronic fistula formation, and one had
      a tear in the right ventricle. Mean hospital stay was 11.28 +/- 2.09 days (range,
      6-16 days). CONCLUSION: Vacuum-assisted closure therapy is a safe, reliable, and
      cost-effective modality of treatment for postoperative mediastinitis. It improves
      the outcome and can be combined with other modalities of conventional treatment,
      especially in high-risk groups such as the elderly or patients with diabetes.

PMID- 24569331
TI  - Transposition of great arteries and partial anomalous pulmonary venous drainage.
AB  - We describe the technical aspects of performing an atrial switch operation in a 4
      year-old boy with d-transposition of the great arteries and partial anomalous
      drainage of the left-sided pulmonary veins. The rarity of the condition is
      discussed. 

PMID- 24569332
TI  - Idiopathic right atrial enlargement.
AB  - A 26-year-old man presented with lower extremity edema and abdominal protrusion
      associated with dyspnea for 5 years, which had increased 7 months earlier.
      Echocardiography demonstrated a huge right atrium of 19.5 * 15.2 cm with a thick
      smoke pattern and severe tricuspid regurgitation. Magnetic resonance imaging
      confirmed intact pericardium. A pulmonary perfusion scan demonstrated multiple
      perfusion defects, suggesting recurrent small pulmonary emboli. Idiopathic
      enlargement of the right atrium was diagnosed. The patient declined surgery. 

PMID- 24569333
TI  - Total anomalous systemic with partial anomalous pulmonary venous connections.
AB  - A 9-year-old girl with cyanosis, dyspnea, and grade II clubbing was diagnosed by
      contrast transthoracic echocardiography and angiocardiography to have an
      anomalous connection of the venae cavae to the physiologic left atrium with
      partial anomalous pulmonary venous connection. Successful surgical correction was
      achieved, and the patient's recovery was uneventful. 

PMID- 24569334
TI  - Surgical treatment for right aortic arch with Kommerell's diverticulum.
AB  - Kommerell's diverticulum causes compression of the esophagus between the aberrant
      origin of the left subclavian artery and ascending aorta, leading to dysphagia or
      dyspnea. We describe 3 cases of successful surgical treatment of right aortic
      arch with Kommerell's diverticulum and aberrant origin of the left subclavian
      artery, using a right anterolateral partial sternotomy. This allows both
      resection of the Kommerell's diverticulum as well as reconstruction of the
      aberrant origin of the left subclavian artery anatomically. 

PMID- 24569335
TI  - Unusual heart transplantation for iterative disinsertion of mitral prosthesis.
AB  - Heart transplantation is the gold standard of care for end-stage heart failure,
      usually associated with an impairment of left ventricular systolic function. We
      describe a case of heart transplantation in a 58-year-old man with normal left
      ventricular systolic function, because of recurrent mitral prosthesis
      disinsertion after multiple reoperations for infective endocarditis. 

PMID- 24569336
TI  - Mediastinal bronchogenic cyst compressing left recurrent laryngeal nerve.
AB  - A 15-year-old boy developed recurrent laryngeal nerve compression by a
      bronchogenic cyst, causing recurrent choking. Bronchogenic cyst compressing the
      recurrent laryngeal nerve is unusual. The patient had a normal voice and
      occasional choking with periods of normalcy in between. A left posterolateral
      thoracotomy was performed and cyst was excised. Histopathology revealed
      bronchogenic cyst. 

PMID- 24569337
TI  - Lung cancer with sarcoid reaction in the lymph nodes following chemoradiotherapy.
AB  - This report describes a case of lung cancer with sarcoid reaction following
      chemoradiotherapy, showing false-positive accumulation of (18)F
      fluorodeoxyglucose on positron-emission tomography in a 55-year-old man.
      Treatment-related sarcoid reaction should be considered when the accumulation of
      (18)F-fluorodeoxyglucose shows rapid extension in the course of treatment. 

PMID- 24569338
TI  - Cavernous hemangioma arising from the diaphragm.
AB  - A 51-year-old man was referred to our hospital with an abnormal nodule in the
      right lung field. Computed tomography revealed a homogeneous nodule adjacent to
      the diaphragm, which appeared to be an extrapulmonary lesion. No hilar or
      mediastinal lymph node swelling was detected, and positron-emission tomography
      showed no significant uptake. At surgery, 2 red papillary tumors were found,
      originating from the right diaphragm, and tumor extirpation was performed. The
      pathological diagnosis was cavernous hemangioma. 

PMID- 24569339
TI  - Right upper lobe torsion following middle lobectomy: a rare complication.
AB  - Middle lobe torsion is a known complication of right upper or lower lobectomy,
      whereas torsion of the upper or lower lobe is extremely rare. We report our
      experience with torsion of the right upper lobe following a middle lobectomy in a
      74-year-old man with non-small-cell lung cancer. 

PMID- 24569340
TI  - Skeletal muscle metastases from lung cancer.
AB  - Lung cancers are diagnosed at a metastatic stage in 40% to 50% of cases. Skeletal
      muscle metastases are rare and usually discovered at autopsy. We report 3 cases
      of skeletal muscle metastasis. Muscular metastasis revealed the cancer in one
      patient. The metastases were asymptomatic in all patients. The diagnosis was
      confirmed histologically in one case and by radiography in the other 2. The
      evolution was characterized by tumor progression and death after 1-7 months. 

PMID- 24569341
TI  - Ruptured thymoma managed via thoracotomy.
AB  - Thymomas rarely present with chest pain due to hemorrhage. This could cause
      shortness of breath if it ruptures into the pleural space, and is best managed
      surgically. We describe the case of an 83-year-old woman who presented with such
      symptoms. Computed tomography showed a ruptured mediastinal mass with pleural
      effusion. She was managed successfully by thoracotomy with excision of the mass
      and drainage of the effusion. Histopathology revealed a ruptured thymoma with
      infarction and necrosis. 

PMID- 24569342
TI  - Breakage of floppy wire during coronary stenting and long-term outcome.

PMID- 24569344
TI  - Virtual collapse of true lumen in acute type A aortic dissection.

PMID- 24569343
TI  - Partial anomalous pulmonary venous return associated with intact atrial septum.

PMID- 24569345
TI  - Inhomogeneously low T2* signal intensity in atrial myxoma.

PMID- 24569346
TI  - Spontaneous left atrial hematoma causing cardiac failure.

PMID- 24569347
TI  - Two questions on bilateral internal mammary artery usage.
AB  - The use of a single internal mammary graft to the left anterior descending artery
      has been the gold standard in surgical coronary revascularization since its
      introduction. However, the take-up rate of use of bilateral internal mammary
      arteries has been slow despite emerging evidence. This has been partly due to the
      worry of postoperative complications, in particular, sternal wound complications.
      Skeletonization of the internal mammary has been proposed as a technique that can
      preserve the sternal microcirculation and therefore reduce this complication. In
      this article, we examine the evidence comparing the skeletonization technique
      versus the conventional pedicled technique for harvesting the internal mammary
      artery. 

PMID- 24569348
TI  - Complete muscle-sparing technique in axillary closure of atrial septal defects.
AB  - Minimally invasive cardiac surgery is gaining wide acceptance. The midaxillary
      approach hides the incision under the right arm. Concerns may arise regarding
      functional recovery should the latissimus dorsi and serratus anterior muscles be
      affected by this maneuver. A modified technique that spares both muscles, without
      splitting their fibers, is described. Six patients have been operated on, with
      excellent functional and cosmetic results, and no side-effects. 

PMID- 24569349
TI  - Antihypertensives are associated with falls in elderly people, study finds.

PMID- 24569350
TI  - Comprehensive analysis of the specificity of transcription activator-like
      effector nucleases.
AB  - A key issue when designing and using DNA-targeting nucleases is specificity.
      Ideally, an optimal DNA-targeting tool has only one recognition site within a
      genomic sequence. In practice, however, almost all designer nucleases available
      today can accommodate one to several mutations within their target site. The
      ability to predict the specificity of targeting is thus highly desirable. Here,
      we describe the first comprehensive experimental study focused on the specificity
      of the four commonly used repeat variable diresidues (RVDs; NI:A, HD:C, NN:G and
      NG:T) incorporated in transcription activator-like effector nucleases (TALEN).
      The analysis of >15 500 unique TALEN/DNA cleavage profiles allowed us to monitor
      the specificity gradient of the RVDs along a TALEN/DNA binding array and to
      present a specificity scoring matrix for RVD/nucleotide association. Furthermore,
      we report that TALEN can only accommodate a relatively small number of position
      dependent mismatches while maintaining a detectable activity at endogenous loci
      in vivo, demonstrating the high specificity of these molecular tools. We thus
      envision that the results we provide will allow for more deliberate choices of
      DNA binding arrays and/or DNA targets, extending our engineering capabilities. 

PMID- 24569351
TI  - Massive parallel-sequencing-based hydroxyl radical probing of RNA accessibility.
AB  - Hydroxyl Radical Footprinting (HRF) is a tried-and-tested method for analysis of
      the tertiary structure of RNA and for identification of protein footprints on
      RNA. The hydroxyl radical reaction breaks accessible parts of the RNA backbone,
      thereby allowing ribose accessibility to be determined by detection of reverse
      transcriptase termination sites. Current methods for HRF rely on reverse
      transcription of a single primer and detection by fluorescent fragments by
      capillary electrophoresis. Here, we describe an accurate and efficient massive
      parallel-sequencing-based method for probing RNA accessibility with hydroxyl
      radicals, called HRF-Seq. Using random priming and a novel barcoding scheme, we
      show that HRF-Seq dramatically increases the throughput of HRF experiments and
      facilitates the parallel analysis of multiple RNAs or experimental conditions.
      Moreover, we demonstrate that HRF-Seq data for the Escherichia coli 16S rRNA
      correlates well with the ribose accessible surface area as determined by X-ray
      crystallography and have a resolution that readily allows the difference in
      accessibility caused by exposure of one side of RNA helices to be observed. 

PMID- 24569353
TI  - Tunnel conductivity switching in a single nanoparticle-based nano floating gate
      memory.
AB  - Nanoparticles (NPs) embedded in a conductive or insulating matrix play a key role
      in memristors and in flash memory devices. However, the role of proximity to the
      interface of isolated NPs has never been directly observed nor fully understood.
      Here we show that a reversible local switching in tunnel conductivity can be
      achieved by applying an appropriate voltage pulse using the tip of a scanning
      tunnelling microscope on NPs embedded in a TiO2 matrix. The resistive switching
      occurs in the TiO2 matrix in correlation to the NPs that are in proximity of the
      surface and it is spatially confined to the single NP size. The tunnel
      conductivity is increased by more than one order of magnitude. The results are
      rationalized by a model that include the charge of NPs that work as a nano
      floating gate inducing local band bending that facilitates charge tunnelling and
      by the formation and redistribution of oxygen vacancies that concentrate in
      proximity of the charged NPs. Our study demonstrates the switching in tunnel
      conductivity in single NP and provides useful information for the understanding
      mechanism or resistive switching. 

PMID- 24569352
TI  - Archaeal aminoacyl-tRNA synthetases interact with the ribosome to recycle tRNAs.
AB  - Aminoacyl-tRNA synthetases (aaRS) are essential enzymes catalyzing the formation
      of aminoacyl-tRNAs, the immediate precursors for encoded peptides in ribosomal
      protein synthesis. Previous studies have suggested a link between tRNA
      aminoacylation and high-molecular-weight cellular complexes such as the
      cytoskeleton or ribosomes. However, the structural basis of these interactions
      and potential mechanistic implications are not well understood. To biochemically
      characterize these interactions we have used a system of two interacting archaeal
      aaRSs: an atypical methanogenic-type seryl-tRNA synthetase and an archaeal ArgRS.
      More specifically, we have shown by thermophoresis and surface plasmon resonance
      that these two aaRSs bind to the large ribosomal subunit with micromolar
      affinities. We have identified the L7/L12 stalk and the proteins located near the
      stalk base as the main sites for aaRS binding. Finally, we have performed a
      bioinformatics analysis of synonymous codons in the Methanothermobacter
      thermautotrophicus genome that supports a mechanism in which the deacylated tRNAs
      may be recharged by aaRSs bound to the ribosome and reused at the next occurrence
      of a codon encoding the same amino acid. These results suggest a mechanism of
      tRNA recycling in which aaRSs associate with the L7/L12 stalk region to recapture
      the tRNAs released from the preceding ribosome in polysomes. 

PMID- 24569354
TI  - Paroxysmal kinesigenic dyskinesia: a frequently misdiagnosed movement disorder.

PMID- 24569355
TI  - Factors associated with adherence to low-tidal volume strategy for acute lung
      injury and acute respiratory distress syndrome and their impacts on outcomes: an
      observational study and propensity analysis.
AB  - BACKGROUND: The purpose of this study was to investigate the factors affecting
      adherence to the low-tidal volume (LTV) strategy in acute lung injury (ALI) and
      acute respiratory distress syndrome (ARDS) and their impacts on outcomes.
      METHODS: This prospective observational study included 111 patients with ALI/ARDS
      admitted to six intensive care units between March 2010 and February 2011. The
      patients were divided into the LTV group, which received a TV <=7.5 mL/kg
      predicted body weight (PBW), and the non-LTV group, which received a TV >7.5
      mL/kg PBW. We studied the association of selected clinical factors and adherence
      to the LTV strategy, and evaluated their impacts on 28-day mortality and 1-year
      mortality by the propensity-match process. RESULTS: Adherence to the LTV strategy
      was only 44%, which was related to lung injury severity (odds ratio [OR]: 3.15,
      P=0.038), muscle relaxant use (OR: 3.28, P=0.031), and depth of sedation (OR:
      0.65, P=0.008). Propensity score-based analysis showed that the LTV group had
      modestly better 28-day survival (P=0.081) and 1-year survival (P=0.067) than the
      non-LTV group. Moreover, muscle relaxant use was strongly associated with
      reducing the risk of death at both 28 days (hazard ratio [HR]: 0.122, 95%
      confidence interval [CI]: 0.027-0.542, P=0.006) and 1 year ([HR]: 0.111, 95%
      [CI]: 0.030-0.408, P=0.001). CONCLUSION: Adherence to the LTV strategy was
      strongly associated with the lung injury score, muscle relaxant use, and depth of
      sedation. Propensity score-based analysis showed that the use of LTV ventilation
      and muscle relaxants reduced 28-day and 1-year mortality in ALI/ARDS patients.

PMID- 24569356
TI  - Cardiac output monitoring with pulmonary versus transpulmonary thermodilution
      during liver transplantation: interchangeable methods?
AB  - BACKGROUND: Liver transplantation (LT) implies hemodynamic instability, making
      invasive monitoring of cardiac output (CO) mandatory. Intermittent thermodilution
      with pulmonary artery catheter (PAC) remains the clinical gold standard to
      measure CO. The agreement between PAC and new monitoring methods in LT needs to
      be further investigated. Our aim is to clarify whether cardiac index (CI)
      measurements with transpulmonary intermittent thermodilution, and continuous
      pulmonary thermodilution methods agree sufficiently with those performed
      intermittently with PAC to be considered interchangeable during LT. METHODS: We
      studied prospectively hemodynamic parameters of 72 consecutive patients
      undergoing LT. Each CI was obtained simultaneously with three different
      techniques: intermittent (PACi) and continuous (CCI) pulmonary artery
      thermodilution with PAC, and intermittent transpulmonary thermodilution (TPTD)
      with PiCCO2 in 8 time points of the procedure, obtaining 1350 paired
      measurements. Exclusion criteria was retransplantation. The statistical Bland
      Altman method for repeated measures was used to assess agreement, and polar plot
      methodology to evaluate trending ability. RESULTS: Analysis of agreement between
      PACi and TPTD measurements (N.=474 paired measurements) showed a bias of -0.42
      L/min/m2, 95% limits of agreement (95%LoA) of +/-1.5 L/min/m2 and percentage
      error of 45%. PACi-CCI comparisons (N.=431) showed bias of -0.02 L/min/m2, 95%LoA
      of +/-1.96 L/min/m2, and percentage error of 64%. These results demonstrated
      questionable clinical agreement between PACi and TPTD, and no agreement between
      PACi and CCI. TPTD and CCI showed poor CO trending ability. CONCLUSION:
      Continuous pulmonary thermodilution with PAC is not an alternative monitoring
      method of CO. Transpulmonary thermodilution CO monitoring with PiCCO2 shows too
      questionable agreement with the clinical gold standard (PACi) being in the limit
      of acceptance to be considered interchangeable during liver transplantation.

PMID- 24569357
TI  - Buprenorphine versus tramadol as perineural adjuvants for postoperative analgesia
      in patients undergoing arthroscopic rotator cuff repair under middle interscalene
      block: a retrospective study.
AB  - BACKGROUND: The aim of this retrospective study was to compare buprenorphine and
      tramadol, in order to assess their different efficacy in prolonging postoperative
      analgesia and their associated side effects when used as perineural adjuvants
      with a local anesthetic. METHODS: The clinical records of 161 consecutive ASA 1-2
      adult patients scheduled for arthroscopic rotator cuff repair and fulfilling the
      inclusion/exclusion criteria were reviewed retrospectively. The anaesthesia was
      performed using the middle interscalene block (MIB). The 161 patients were
      divided into three groups (A, B, T) according to their utilization of
      buprenorphine (B), tramadol (T) or neither of the latter (A) as perineural
      adjuvants: group A (54 patients) - levobupivacaine 0.75%, 0.4 mL/kg; group B (56
      patients) - levobupivacaine 0.75%, 0.4 mL/kg + 0.15 mg buprenorphine; group T (51
      patients) - levobupivacaine 0.75%, 0.4 mL/kg + 100 mg tramadol. RESULTS: The
      results showed that the group treated with buprenorphine benefited from a longer
      post-operative analgesia than that treated with local anesthetic alone
      (P<0.0001). Otherwise, a less evident not statistically significant (P=0.4825)
      difference turned out between the group treated with the anesthetic alone and the
      group treated with tramadol as adjuvant. No difference turned out to be between
      the local anesthetic alone treatment and the tramadol-local anesthetic one
      (P=0.4825; HR=0.863, 95% CI 0.574-1.299); on the contrary, a significant
      difference was demonstrated between the buprenophine-local anesthetic group and
      the local anesthetic alone one (P<0.0001; HR=0.330, 95% CI 0.216-0.530)
      CONCLUSION: Both buprenorphine and tramadol are effective as perineural adjuvants
      used in order to prolong the postoperative analgesia, buprenorphine proving more
      efficacious for this purpose than tramadol.

PMID- 24569358
TI  - Resistive Index or color-Doppler semi-quantitative evaluation of renal perfusion
      by inexperienced physicians: results of a pilot study.
AB  - BACKGROUND: Doppler-based renal resistive index (RI) calculation may help in the
      early detection of acute kidney injury (AKI). Its feasibility and reproducibility
      by inexperienced operators remain unknown. The main objective of this study was
      to compare performances of junior and senior operators in assessing renal
      perfusion using both the semiquantitative color-Doppler scale and RI calculation.
      METHODS: Prospective cohort study performed in 3 ICUs. Inexperienced juniors
      physicians attended a half-day course on renal perfusion assessment using RI
      calculation and color-Doppler (from 0, absence of renal perfusion; to 3, renal
      vessels identifiable in the entire field of view). Junior and senior operators
      used both methods in 69 mechanically ventilated patients, in blind fashion.
      RESULTS: Failure to obtain RI occurred for a junior operator in a single patient.
      RI and color-Doppler semi-quantitative values obtained by operators were
      correlated (r2=0.64 and r2=0.61, respectively). Systematic bias across operators
      as assessed using Bland-Altman plots was negligible (-0.001 and -0.29,
      respectively), although precision was limited (95% confidence intervals, +0.105
      to -0.107 and +0.98 to -1.04, respectively). RI calculation and semi-quantitative
      assessment performed well for diagnosing persistent AKI (area under the receiver
      operating characteristic curve, 0.84 [95% confidence interval, 0.73-0.97] and
      0.87 [0.77-0.97], respectively). CONCLUSION: A brief course on renal Doppler
      allowed inexperienced operators to assess effectively renal perfusion with a good
      reliability when compared to senior operators. In addition, our results suggest
      the good diagnostic performance of both Doppler-based RI and semi-quantitative
      renal perfusion assessment in predicting short-term renal dysfunction
      reversibility.

PMID- 24569360
TI  - Anticoagulation therapy: Apixaban is cost-effective.

PMID- 24569361
TI  - Interventional cardiology: Causes of death after PCI.

PMID- 24569363
TI  - Public health: Increased risk of cardiovascular death in adults who eat high
      levels of added sugar.

PMID- 24569364
TI  - NRF2 mitigates radiation-induced hematopoietic death.
AB  - Fractionated, high-dose total body irradiation (TBI) is used therapeutically to
      myeloablate and immune suppress patients undergoing hematopoietic stem cell (HSC)
      transplantation. Acute exposure to ionizing radiation can have fatal effects on
      the hematopoietic and immune systems. Currently, therapies aimed at ameliorating
      ionizing radiation-associated toxicities are limited. In the February 2014 issue
      of the JCI, Kim and colleagues demonstrated that induction of nuclear factor
      erythroid 2-related factor 2 (NRF2) enhances HSC regeneration and increases
      survival following ionizing radiation exposure in mice. The results of this study
      suggest that NRF2 is a novel potential target for the development of therapeutics
      aimed at mitigating the toxicities of ionizing radiation exposure. 

PMID- 24569365
TI  - PPARgamma in emphysema: blunts the damage and triggers repair?
AB  - Cigarette smoke is the most common cause of pulmonary emphysema, which results in
      an irreversible loss of lung structure and function. Th1 and Th17 immune
      responses have been implicated in emphysema pathogenesis; however, the drivers of
      emphysema-associated immune dysfunction are not fully understood. In this issue
      of the JCI, Shan and colleagues found that peroxisome proliferator-activated
      receptor gamma (PPARgamma) is downregulated in APCs isolated from the lungs of
      emphysematous chronic smokers and mice exposed to cigarette smoke. Furthermore,
      treatment with a PPARgamma agonist prevented emphysema development and appeared
      to reduce emphysema-associated lung volume expansion in mice exposed to cigarette
      smoke. Further work will need to be done to evaluate the potential of PPARgamma
      agonists to restore lung capacity in emphysematous patients. 

PMID- 24569366
TI  - Fanning the flames to regenerate the heart.
AB  - Damage to the adult mammalian heart is irreversible, and lost cells are not
      replaced through regeneration. In neonatal mice, prior to P7, heart tissue can be
      regenerated after injury; however, the factors that facilitate cardiac
      regeneration in the neonatal heart are not known. In this issue of the JCI,
      Aurora and colleagues evaluated the immune response following myocardial
      infarction in P1 mice compared with that in P14 mice, which have lost their
      regenerative capacity, and identified a population of macrophages as mediators of
      cardiac repair. Further understanding of the immune modulators that promote the
      regenerative properties of this macrophage subset could potentially be exploited
      to recapitulate regenerative function in the adult heart. 

PMID- 24569362
TI  - Impact of ethnicity on cardiac adaptation to exercise.
AB  - The increasing globalization of sport has resulted in athletes from a wide range
      of ethnicities emerging onto the world stage. Fuelled by the untimely death of a
      number of young professional athletes, data generated from the parallel increase
      in preparticipation cardiovascular evaluation has indicated that ethnicity has a
      substantial influence on cardiac adaptation to exercise. From this perspective,
      the group most intensively studied comprises athletes of African or Afro
      Caribbean ethnicity (black athletes), an ever-increasing number of whom are
      competing at the highest levels of sport and who often exhibit profound
      electrical and structural cardiac changes in response to exercise. Data on other
      ethnic cohorts are emerging, but remain incomplete. This Review describes our
      current knowledge on the impact of ethnicity on cardiac adaptation to exercise,
      starting with white athletes in whom the physiological electrical and structural
      changes--collectively termed the 'athlete's heart'--were first described.
      Discussion of the differences in the cardiac changes between ethnicities, with a
      focus on black athletes, and of the challenges that these variations can produce
      for the evaluating physician is also provided. The impact of ethnically mediated
      changes on preparticipation cardiovascular evaluation is highlighted,
      particularly with respect to false positive results, and potential genetic
      mechanisms underlying racial differences in cardiac adaptation to exercise are
      described.

PMID- 24569367
TI  - Neurogenesis or non-neurogenesis: that is the question.
AB  - Neural stem/precursor cells (NPCs) that reside within germinal niches of the
      adult CNS have more complex roles than previously expected. In addition to their
      well-documented neurogenic functions, emerging evidence indicates that NPCs exert
      non-neurogenic functions that contribute to the regulation and preservation of
      tissue homeostasis under both physiological and pathological conditions. In this
      issue of the JCI, Mohammad et al. found that DCs efficiently patrol the CNS only
      when the germinal niche of the subventricular zone functions properly. Indeed,
      DCs traveled from the ventricles along the rostral migratory stream to the
      olfactory bulb (a cervical lymph node access point) to dampen anti-CNS immune
      responses. The authors' findings further support a non-neurogenic role for NPCs
      in maintaining tissue homeostasis and promoting tissue protection in the adult
      brain. 

PMID- 24569368
TI  - Dynamin 2 the rescue for centronuclear myopathy.
AB  - Centronuclear myopathy is a lethal muscle disease. The most severe form of the
      disease, X-linked centronuclear myopathy, is due to mutations in the gene
      encoding myotubularin (MTM1), while mutations in dynamin 2 (DNM2) and amphiphysin
      2/BIN1 (AMPH2) cause milder forms of myopathy. MTM1 is a lipid phosphatase, and
      mutations that disrupt this activity cause severe muscle wasting. In this issue
      of the JCI, Cowling and colleagues report on their finding of increased DNM2
      levels in human and mouse muscle with MTM1 mutations. Partial reduction of Dnm2
      in mice harboring Mtm1 mutations remarkably rescued muscle wasting and lethality,
      and this effect was muscle specific. DNM2 regulates membrane trafficking through
      vesicular scission, and it is presumed that reducing this activity accounts for
      improved outcome in X-linked centronuclear myopathy. 

PMID- 24569369
TI  - Translational enhancers of EAAT2: therapeutic implications for neurodegenerative
      disease.
AB  - Glutamate excitotoxicity contributes to the neuronal injury and death associated
      with many neurodegenerative diseases. The glutamate transporter EAAT2, which is
      primarily localized on astrocytic processes, facilitates glutamate clearance from
      synapses, thus preventing neuronal damage. In this issue of the JCI, Kong et al.
      characterize a compound that upregulates EAAT2 translation, thereby increasing
      glutamate uptake by glial cells. Furthermore, this strategy for alleviating
      excitotoxicity was found to be beneficial in mouse models of both amyotrophic
      lateral sclerosis (ALS) and epilepsy, suggesting that future development in this
      chemical series may lead to much-needed treatments for these disorders. 

PMID- 24569370
TI  - Dangerous liaisons: flirtations between oncogenic BRAF and GRP78 in drug
      resistant melanomas.
AB  - BRAF mutations in aggressive melanomas result in kinase activation. BRAF
      inhibitors reduce BRAF(V600E) tumors, but rapid resistance follows. In this issue
      of the JCI, Ma and colleagues report that vemurafenib activates ER stress and
      autophagy in BRAF(V600E) melanoma cells, through sequestration of the ER
      chaperone GRP78 by the mutant BRAF and subsequent PERK activation. In preclinical
      studies, treating vemurafenib-resistant melanoma with a combination of
      vemurafenib and an autophagy inhibitor reduced tumor load. Further work is needed
      to establish clinical relevance of this resistance mechanism and demonstrate
      efficacy of autophagy and kinase inhibitor combinations in melanoma treatment.

PMID- 24569371
TI  - Working toward immune tolerance in lung transplantation.
AB  - Long-term allograft survival is a major challenge facing solid organ
      transplantation. Recent studies have shown a negative correlation between
      infiltration of memory T cells and allograft survival. Furthermore, blockade of
      leukocyte activation increases acceptance of transplanted organs, including
      heart, liver, and kidney. Lung allografts are associated with high rates of
      rejection, and therapies that increase acceptance of other transplanted organs
      have not translated into the lung. In this issue of the JCI, Krupnick and
      colleagues demonstrate in a murine model that lung allograft acceptance requires
      infiltration of a specific T cell population into the graft. This study
      highlights the unique immunobiology of the lung and the complexity of lung
      transplant tolerance. 

PMID- 24569372
TI  - Small-molecule activator of glutamate transporter EAAT2 translation provides
      neuroprotection.
AB  - Glial glutamate transporter EAAT2 plays a major role in glutamate clearance in
      synaptic clefts. Several lines of evidence indicate that strategies designed to
      increase EAAT2 expression have potential for preventing excitotoxicity, which
      contributes to neuronal injury and death in neurodegenerative diseases. We
      previously discovered several classes of compounds that can increase EAAT2
      expression through translational activation. Here, we present efficacy studies of
      the compound LDN/OSU-0212320, which is a pyridazine derivative from one of our
      lead series. In a murine model, LDN/OSU-0212320 had good potency, adequate
      pharmacokinetic properties, no observed toxicity at the doses examined, and low
      side effect/toxicity potential. Additionally, LDN/OSU-0212320 protected cultured
      neurons from glutamate-mediated excitotoxic injury and death via EAAT2
      activation. Importantly, LDN/OSU-0212320 markedly delayed motor function decline
      and extended lifespan in an animal model of amyotrophic lateral sclerosis (ALS).
      We also found that LDN/OSU-0212320 substantially reduced mortality, neuronal
      death, and spontaneous recurrent seizures in a pilocarpine-induced temporal lobe
      epilepsy model. Moreover, our study demonstrated that LDN/OSU-0212320 treatment
      results in activation of PKC and subsequent Y-box-binding protein 1 (YB-1)
      activation, which regulates activation of EAAT2 translation. Our data indicate
      that the use of small molecules to enhance EAAT2 translation may be a therapeutic
      strategy for the treatment of neurodegenerative diseases. 

PMID- 24569373
TI  - Serum IgE clearance is facilitated by human FcepsilonRI internalization.
AB  - The high-affinity IgE receptor FcepsilonRI is constitutively expressed in mast
      cells and basophils and is required for transmitting stimulatory signals upon
      engagement of IgE-bound allergens. FcepsilonRI is also constitutively expressed
      in dendritic cells (DCs) and monocytes in humans; however, the specific functions
      of the FcepsilonRI expressed by these cells are not completely understood. Here,
      we found that FcepsilonRI expressed by human blood DC antigen 1-positive (BDCA1+)
      DCs and monocytes, but not basophils, traffics to endolysosomal compartments
      under steady-state conditions. Furthermore, IgE bound to FcepsilonRI on BDCA1+
      DCs was rapidly endocytosed, transported to the lysosomes, and degraded in vitro.
      IgE injected into mice expressing human FcepsilonRIalpha (FCER1A-Tg mice) was
      endocytosed by conventional DCs and monocytes, and endocytosis was associated
      with rapid clearance of circulating IgE from these mice. Importantly, this rapid
      IgE clearance was dependent on monocytes or DCs but not basophils. These findings
      strongly suggest that constitutive internalization of human FcepsilonRI by DCs
      and monocytes distinctively contributes to serum IgE clearance. 

PMID- 24569374
TI  - Targeting ER stress-induced autophagy overcomes BRAF inhibitor resistance in
      melanoma.
AB  - Melanomas that result from mutations in the gene encoding BRAF often become
      resistant to BRAF inhibition (BRAFi), with multiple mechanisms contributing to
      resistance. While therapy-induced autophagy promotes resistance to a number of
      therapies, especially those that target PI3K/mTOR signaling, its role as an
      adaptive resistance mechanism to BRAFi is not well characterized. Using tumor
      biopsies from BRAF(V600E) melanoma patients treated either with BRAFi or with
      combined BRAF and MEK inhibition, we found that BRAFi-resistant tumors had
      increased levels of autophagy compared with baseline. Patients with higher levels
      of therapy-induced autophagy had drastically lower response rates to BRAFi and a
      shorter duration of progression-free survival. In BRAF(V600E) melanoma cell
      lines, BRAFi or BRAF/MEK inhibition induced cytoprotective autophagy, and
      autophagy inhibition enhanced BRAFi-induced cell death. Shortly after BRAF
      inhibitor treatment in melanoma cell lines, mutant BRAF bound the ER stress
      gatekeeper GRP78, which rapidly expanded the ER. Disassociation of GRP78 from the
      PKR-like ER-kinase (PERK) promoted a PERK-dependent ER stress response that
      subsequently activated cytoprotective autophagy. Combined BRAF and autophagy
      inhibition promoted tumor regression in BRAFi-resistant xenografts. These data
      identify a molecular pathway for drug resistance connecting BRAFi, the ER stress
      response, and autophagy and provide a rationale for combination approaches
      targeting this resistance pathway.

PMID- 24569375
TI  - Agonistic induction of PPARgamma reverses cigarette smoke-induced emphysema.
AB  - The development of emphysema in humans and mice exposed to cigarette smoke is
      promoted by activation of an adaptive immune response. Lung myeloid dendritic
      cells (mDCs) derived from cigarette smokers activate autoreactive Th1 and Th17
      cells. mDC-dependent activation of T cell subsets requires expression of the SPP1
      gene, which encodes osteopontin (OPN), a pleiotropic cytokine implicated in
      autoimmune responses. The upstream molecular events that promote SPP1 expression
      and activate mDCs in response to smoke remain unknown. Here, we show that
      peroxisome proliferator-activated receptor gamma (PPARG/Pparg) expression was
      downregulated in mDCs of smokers with emphysema and mice exposed to chronic
      smoke. Conditional knockout of PPARgamma in APCs using Cd11c-Cre Pparg(flox/flox)
      mice led to spontaneous lung inflammation and emphysema that resembled the
      phenotype of smoke-exposed mice. The inflammatory phenotype of Cd11c-Cre
      Pparg(flox/flox) mice required OPN, suggesting an antiinflammatory mechanism in
      which PPARgamma negatively regulates Spp1 expression in the lung. A 2-month
      treatment with a PPARgamma agonist reversed emphysema in WT mice despite
      continual smoke exposure. Furthermore, endogenous PPARgamma agonists were reduced
      in the plasma of smokers with emphysema. These findings reveal a proinflammatory
      pathway, in which reduced PPARgamma activity promotes emphysema, and suggest that
      targeting this pathway in smokers could prevent and reverse emphysema.

PMID- 24569376
TI  - Reducing dynamin 2 expression rescues X-linked centronuclear myopathy.
AB  - Centronuclear myopathies (CNM) are congenital disorders associated with muscle
      weakness and abnormally located nuclei in skeletal muscle. An autosomal dominant
      form of CNM results from mutations in the gene encoding dynamin 2 (DNM2), and
      loss-of-function mutations in the gene encoding myotubularin (MTM1) result in X
      linked CNM (XLCNM, also called myotubular myopathy), which promotes severe
      neonatal hypotonia and early death. Currently, no effective treatments exist for
      XLCNM. Here, we found increased DNM2 levels in XLCNM patients and a mouse model
      of XLCNM (Mtm1(-/y)). Generation of Mtm1(-/y) mice that were heterozygous for
      Dnm2 revealed that reduction of DNM2 in XLCNM mice restored life span, whole-body
      strength, and diaphragm function and increased muscle strength. Additionally,
      classic CNM-associated histological features, including fiber atrophy and nuclei
      mispositioning, were absent or reduced. Ultrastructural analysis revealed
      improvement of sarcomere organization and triad structures. Skeletal muscle
      specific decrease of Dnm2 during embryogenesis or in young mice after disease
      onset revealed that the rescue associated with downregulation of Dnm2 is cell
      autonomous and is able to stop and potentially revert XLCNM progression. These
      data indicate that MTM1 and DNM2 regulate muscle organization and force through a
      common pathway. Furthermore, despite DNM2 being a key mechanoenzyme, its
      reduction is beneficial for XLCNM and represents a potential therapeutic approach
      for patients.

PMID- 24569377
TI  - Central memory CD8+ T lymphocytes mediate lung allograft acceptance.
AB  - Memory T lymphocytes are commonly viewed as a major barrier for long-term
      survival of organ allografts and are thought to accelerate rejection responses
      due to their rapid infiltration into allografts, low threshold for activation,
      and ability to produce inflammatory mediators. Because memory T cells are usually
      associated with rejection, preclinical protocols have been developed to target
      this population in transplant recipients. Here, using a murine model, we found
      that costimulatory blockade-mediated lung allograft acceptance depended on the
      rapid infiltration of the graft by central memory CD8+ T cells
      (CD44(hi)CD62L(hi)CCR7+). Chemokine receptor signaling and alloantigen
      recognition were required for trafficking of these memory T cells to lung
      allografts. Intravital 2-photon imaging revealed that CCR7 expression on CD8+ T
      cells was critical for formation of stable synapses with antigen-presenting
      cells, resulting in IFN-gamma production, which induced NO and downregulated
      alloimmune responses. Thus, we describe a critical role for CD8+ central memory T
      cells in lung allograft acceptance and highlight the need for tailored approaches
      for tolerance induction in the lung.

PMID- 24569378
TI  - Immune cell trafficking from the brain maintains CNS immune tolerance.
AB  - In the CNS, no pathway dedicated to immune surveillance has been characterized
      for preventing the anti-CNS immune responses that develop in autoimmune
      neuroinflammatory disease. Here, we identified a pathway for immune cells to
      traffic from the brain that is associated with the rostral migratory stream
      (RMS), which is a forebrain source of newly generated neurons. Evaluation of
      fluorescently labeled leukocyte migration in mice revealed that DCs travel via
      the RMS from the CNS to the cervical LNs (CxLNs), where they present antigen to T
      cells. Pharmacologic interruption of immune cell traffic with the mononuclear
      cell-sequestering drug fingolimod influenced anti-CNS T cell responses in the
      CxLNs and modulated experimental autoimmune encephalomyelitis (EAE) severity in a
      mouse model of multiple sclerosis (MS). Fingolimod treatment also induced EAE in
      a disease-resistant transgenic mouse strain by altering DC-mediated Treg
      functions in CxLNs and disrupting CNS immune tolerance. These data describe an
      immune cell pathway that originates in the CNS and is capable of dampening anti
      CNS immune responses in the periphery. Furthermore, these data provide insight
      into how fingolimod treatment might exacerbate CNS neuroinflammation in some
      cases and suggest that focal therapeutic interventions, outside the CNS have the
      potential to selectively modify anti-CNS immunity. 

PMID- 24569379
TI  - Cell-specific translational profiling in acute kidney injury.
AB  - Acute kidney injury (AKI) promotes an abrupt loss of kidney function that results
      in substantial morbidity and mortality. Considerable effort has gone toward
      identification of diagnostic biomarkers and analysis of AKI-associated molecular
      events; however, most studies have adopted organ-wide approaches and have not
      elucidated the interplay among different cell types involved in AKI
      pathophysiology. To better characterize AKI-associated molecular and cellular
      events, we developed a mouse line that enables the identification of
      translational profiles in specific cell types. This strategy relies on CRE
      recombinase-dependent activation of an EGFP-tagged L10a ribosomal protein
      subunit, which allows translating ribosome affinity purification (TRAP) of mRNA
      populations in CRE-expressing cells. Combining this mouse line with cell type
      specific CRE-driver lines, we identified distinct cellular responses in an
      ischemia reperfusion injury (IRI) model of AKI. Twenty-four hours following IRI,
      distinct translational signatures were identified in the nephron, kidney
      interstitial cell populations, vascular endothelium, and macrophages/monocytes.
      Furthermore, TRAP captured known IRI-associated markers, validating this
      approach. Biological function annotation, canonical pathway analysis, and in situ
      analysis of identified response genes provided insight into cell-specific injury
      signatures. Our study provides a deep, cell-based view of early injury-associated
      molecular events in AKI and documents a versatile, genetic tool to monitor cell
      specific and temporal-specific biological processes in disease modeling. 

PMID- 24569381
TI  - Maternal prepregnancy obesity and child neurodevelopment in the Collaborative
      Perinatal Project.
AB  - OBJECTIVES: To examine the association between maternal prepregnancy weight and
      child neurodevelopment, and the effect of gestational weight gain. METHODS: Using
      the U.S. Collaborative Perinatal Project data, 1959-76, a total of 30,212 women
      with a calculable prepregnancy body mass index (BMI) and gestational weight gain,
      and term singleton children followed up for more than 7 years were included in
      this study. Intelligence quotient (IQ) was measured at 7 years of age by Wechsler
      Intelligence Scales. RESULTS: Maternal prepregnancy BMI displayed inverted U
      shaped associations with child IQ after adjustment for maternal age, maternal
      education levels, maternal race, marital status, socioeconomic status, smoking
      during pregnancy, parity and study center. Women with BMI at around 20 kg/m2
      appeared to have the highest offspring IQ scores. After controlling for familial
      factors in the siblings' sample, maternal obesity (BMI>=30.0 kg/m2) was
      associated with lower Full-scale IQ (adjusted beta=-2.0, 95% confidence interval 
      3.5 to -0.5), and Verbal scale IQ (adjusted beta=-2.5, 95% confidence interval 
      4.0 to -1.0), using BMI of 18.5-24.9 kg/m2 as the reference category. Compared
      with children born to normal-weight women who gained 21-25 lb. during pregnancy,
      those born to obese women who gained more than 40 lb. had 6.5 points deficit in
      IQ after adjustment for potential confounders. CONCLUSIONS: Maternal prepregnancy
      obesity was associated with lower child IQ, and excessive weight gain accelerated
      the association. With obesity rising steadily, these results appear to raise
      serious public health concerns.

PMID- 24569380
TI  - Macrophages are required for neonatal heart regeneration.
AB  - Myocardial infarction (MI) leads to cardiomyocyte death, which triggers an immune
      response that clears debris and restores tissue integrity. In the adult heart,
      the immune system facilitates scar formation, which repairs the damaged
      myocardium but compromises cardiac function. In neonatal mice, the heart can
      regenerate fully without scarring following MI; however, this regenerative
      capacity is lost by P7. The signals that govern neonatal heart regeneration are
      unknown. By comparing the immune response to MI in mice at P1 and P14, we
      identified differences in the magnitude and kinetics of monocyte and macrophage
      responses to injury. Using a cell-depletion model, we determined that heart
      regeneration and neoangiogenesis following MI depends on neonatal macrophages.
      Neonates depleted of macrophages were unable to regenerate myocardia and formed
      fibrotic scars, resulting in reduced cardiac function and angiogenesis.
      Immunophenotyping and gene expression profiling of cardiac macrophages from
      regenerating and nonregenerating hearts indicated that regenerative macrophages
      have a unique polarization phenotype and secrete numerous soluble factors that
      may facilitate the formation of new myocardium. Our findings suggest that
      macrophages provide necessary signals to drive angiogenesis and regeneration of
      the neonatal mouse heart. Modulating inflammation may provide a key therapeutic
      strategy to support heart regeneration. 

PMID- 24569382
TI  - Intergenerational determinants of offspring size at birth: a life course and
      graphical analysis using the Aberdeen Children of the 1950s Study (ACONF).
AB  - BACKGROUND: Size at birth has taken on renewed significance due to its now well
      established association with many health and health-related outcomes in both the
      immediate perinatal period and across the entire life course. Optimizing fetal
      growth to improve both neonatal survival and population health is the focus of
      much research and policy development, although most efforts have concentrated on
      either the period of pregnancy itself or the period immediately preceding it.
      METHODS: Intergenerational data linked to the Aberdeen Children of the 1950s
      (ACONF) study were used to examine the influence of grandparental and parental
      life course biological and social variables on the distribution of offspring size
      at birth. Guided stepwise multivariable methods and a graphical approach were
      used to assess the relative importance of these temporally ordered and highly
      correlated life course measures. RESULTS: Both distal and proximal grandparental
      and parental life course biological and social factors predicted offspring size
      at birth. Inequalities in size at birth, according to adult maternal
      socioeconomic indicators, were found to be largely generated by the continuity of
      the social environment across generations, and the inequalities in maternal early
      life growth were predicted by the adult grandparental social environment during
      the mother's early life. Mother's own size at birth predicted her offspring's
      intrauterine growth, independent of her adult biological and social
      characteristics. CONCLUSIONS: A mother's childhood social environment and her
      early growth are both important predictors of her offspring's size at birth.
      Population strategies aimed at optimizing size at birth require broader social
      and intergenerational considerations, in addition to focusing on the health of
      mothers in the immediate pregnancy period.

PMID- 24569384
TI  - Letter from the editor.

PMID- 24569385
TI  - Fluctuation in hearing thresholds during recovery from childhood bacterial
      meningitis.
AB  - BACKGROUND: Hearing loss from childhood bacterial meningitis is believed to
      develop early and have little tendency for recovery. We performed serial hearing
      evaluations in a large number of children with bacterial meningitis in Luanda,
      Angola to clarify if, and how often, the result changed. METHODS: Children with
      confirmed bacterial meningitis and hearing evaluations on admission, day 7 of
      treatment and the follow-up visit formed the study group. Hearing was tested by
      auditory brainstem response audiometry using stimuli of 40 dB, 60 dB and 80 dB.
      Threshold changes are described between the composite levels of 40/60 dB and
      80/>80 dB. RESULTS: In all, 235 ears were tested. While the <= 60 dB and >= 80 dB
      levels were maintained through all 3 examinations in 54% and 5% of ears,
      respectively, changes occurred in 41%. Deterioration from the <= 60 dB level to
      >= 80 dB was found in 10% of the ears transiently and in 7% permanently.
      Improvement from the >= 80 dB level to <= 60 dB occurred in 22% of the ears. Half
      of the ears with >= 80 dB impairment at the follow-up visit arrived with this
      finding; the others lost hearing later. Maintaining the <= 60 dB level throughout
      was associated with milder disease (P = 0.003), fewer convulsions (P < 0.0001)
      and older age (P = 0.009). CONCLUSIONS: Almost half of the ears showed threshold
      changes after admission during recovery from bacterial meningitis, most
      frequently improvement of initially severely impaired hearing, but some normal
      ears or with moderate impairment became severely impaired.

PMID- 24569386
TI  - Parental views on childhood influenza vaccination.

PMID- 24569383
TI  - 3D multifunctional integumentary membranes for spatiotemporal cardiac
      measurements and stimulation across the entire epicardium.
AB  - Means for high-density multiparametric physiological mapping and stimulation are
      critically important in both basic and clinical cardiology. Current conformal
      electronic systems are essentially 2D sheets, which cannot cover the full
      epicardial surface or maintain reliable contact for chronic use without sutures
      or adhesives. Here we create 3D elastic membranes shaped precisely to match the
      epicardium of the heart via the use of 3D printing, as a platform for deformable
      arrays of multifunctional sensors, electronic and optoelectronic components. Such
      integumentary devices completely envelop the heart, in a form-fitting manner, and
      possess inherent elasticity, providing a mechanically stable biotic/abiotic
      interface during normal cardiac cycles. Component examples range from actuators
      for electrical, thermal and optical stimulation, to sensors for pH, temperature
      and mechanical strain. The semiconductor materials include silicon, gallium
      arsenide and gallium nitride, co-integrated with metals, metal oxides and
      polymers, to provide these and other operational capabilities. Ex vivo
      physiological experiments demonstrate various functions and methodological
      possibilities for cardiac research and therapy. 

PMID- 24569387
TI  - Detection of a NDM-1-producing Klebsiella pneumoniae (ST22) clinical isolate at a
      pediatric hospital in Mexico.

PMID- 24569388
TI  - Effectiveness of 2 rotavirus vaccines against rotavirus disease in Taiwanese
      infants.
AB  - BACKGROUND: Two rotavirus (RV) vaccines (Rotarix and RotaTeq) are available on
      the private market in Taiwan, but are not recommended for routine use. We
      examined RV vaccine effectiveness (VE) against severe RV acute gastroenteritis
      (AGE) among Taiwanese infants to inform policymakers on the potential benefits of
      national RV vaccine introduction. METHODS: From May 2009 to April 2011, a case
      control assessment of VE against severe RV AGE was conducted at 3 hospital-based
      surveillance sites in Taiwan. Case-patients included children aged 8-35 months,
      hospitalized with laboratory-confirmed RV AGE. Controls included children age
      matched within 1 month of age of the case-patient, hospitalized with RV-negative
      AGE or seen for non-AGE illnesses at the same hospitals. Vaccination history was
      confirmed through vaccination card or hospital record review. VE was calculated
      as (1--odds ratio of vaccination) * 100%. RESULTS: We enrolled 184 case-patients
      with RV AGE, 904 RV-negative AGE and 909 non-AGE controls. Two-dose Rotarix
      series VE against RV gastroenteritis hospitalization was 90.4% [95% confidence
      interval (CI): 70.3%, 98.1%) and 92.5% (95% CI: 77.1%, 98.5%) with RV-negative
      AGE and non-AGE controls, respectively. Three-dose RotaTeq series VE was 96.8%
      (95% CI: 82.3%, 100%) and 97.1% (95% CI: 84%, 100%) with RV-negative AGE and non
      AGE controls, respectively. CONCLUSIONS: Both vaccines provided excellent
      protection against severe RV AGE hospitalization. Addition of RV vaccination into
      Taiwan's National Immunization Program could substantially decrease AGE
      hospitalizations among children <3 years. Our findings should help inform
      policymakers in Taiwan and other similar Asian countries when deciding whether to
      include RV vaccination into their national immunization programs.

PMID- 24569389
TI  - Chromane helicity rule--scope and challenges based on an ECD study of various
      trolox derivatives.
AB  - The validity of the chromane helicity rule correlating the sense of twist within
      the dihydropyran ring with the CD sign of the (1)Lb band observed at ca. 290 nm
      in their electronic circular dichroism (ECD) spectra is examined using a set of
      natural (S)-trolox derivatives. To investigate both the scope and the limitations
      of the rule a combination of ECD spectroscopy, especially the temperature
      dependence of the ECD spectra, single crystal X-ray diffraction analyses, and
      density functional theory (DFT) calculations was used. A thorough conformational
      analysis supported by the X-ray data led to the identification of predominant
      conformers. Then, a comparison of the experimental ECD spectra with the spectra
      simulated by TDDFT calculations allowed for a reasonable interpretation of the
      accumulated data. The results clearly indicated that to avoid the possibility of
      erroneous conclusions the chromane helicity rule should be used with great
      caution. This is likely related to the conformational flexibility of tested
      compounds by which conformers of different helicities can be produced. Therefore,
      based on the results presented here, it is strongly recommended that the
      conclusions derived from analysis of experimental data are supported with the
      appropriate theoretical computations. 

PMID- 24569390
TI  - Aggregation induced emission enhancement from Bathophenanthroline microstructures
      and its potential use as sensor of mercury ions in water.
AB  - Bathophenanthroline (BA) microstructures of various morphologies have been
      synthesized using a reprecipitation method. The morphologies of the particles are
      characterized using optical and scanning electron microscopy (SEM) methods. An
      aqueous dispersion of BA microstructures shows aggregation induced emission
      enhancement (AIEE) compared to BA in a good solvent, THF. This luminescent
      property of aggregated BA hydrosol is used for the selective detection of trace
      amounts of mercury ion (Hg(2+)) in water. It is observed that Hg(2+) ions can
      quench the photoluminescence (PL) intensity of BA aggregates even at very low
      concentrations, compared to other heavy metal ions e.g. nickel (Ni(2+)),
      manganese (Mn(2+)), cadmium (Cd(2+)), cobalt (Co(2+)), copper (Cu(2+)), ferrous
      (Fe(2+)) and zinc (Zn(2+)). This strong fluorescence quenching of aggregated BA
      in the presence of Hg(2+) ions has been explained as a complex interplay between
      the ground state complexation between BA and Hg(2+) ions and external heavy atom
      induced perturbation by Hg(2+) ions on the excited states of the fluorophore BA. 

PMID- 24569391
TI  - A widely applicable plasma renin activity assay by LC-MS/MS with offline solid
      phase extraction.
AB  - BACKGROUND: The measurement of plasma renin activity using LC-MS/MS is an
      attractive alternative to radioimmunoassay techniques. A published method for
      renin activity by LC-MS/MS uses equipment that is not available in all LC-MS/MS
      laboratories. Here, we present an offline modification to allow users of LC-MS/MS
      to perform this analysis without specialist equipment. METHODS: Samples were
      prepared in duplicate and incubated for 6.5 h and 24 h. Solid phase extraction
      was performed offline using Waters Oasis MAX ion-exchange 96-well plate. A method
      comparison was performed between this assay and a previously published assay
      using on-line solid phase extraction. RESULTS: The offline method for plasma
      rennin activity gave similar results to the on-line method across the
      concentration range. Analytical performance was also found to be comparable and
      the use of a 24 h incubation for low samples was also deemed unnecessary.
      DISCUSSION: The method described is an acceptable alternative to a previously
      published assay which does not require the use of highly specialist equipment and
      will be applicable to the majority of LC-MS/MS users.

PMID- 24569392
TI  - Prevalence of antiphospholipid antibodies in patients with sterility undergoing
      'in vitro' fertilization.

PMID- 24569393
TI  - Validation of a disease-specific health-related quality of life measure in adult
      Italian patients with systemic lupus erythematosus: LupusQoL-IT.
AB  - OBJECTIVE: The objective of this paper is to assess the validity of a
      linguistically validated version of the Lupus Quality of Life (LupusQoL((c))) in
      Italian patients affected by systemic lupus erythematosus (SLE). METHODS:
      Consecutive SLE patients completed the Italian version of the LupusQoL((c)) and
      the Short Form (SF)-36. Disease activity was evaluated by the SLE disease
      activity Index-2000 (SLEDAI-2 K), and chronic damage by the Systemic Lupus
      International Collaborating Clinics/American College Rheumatology (ACR) Damage
      Index score (SDI). Internal consistency and test-retest reliability, convergent
      and discriminant validity were examined. Factor analysis with varimax rotation
      was performed. RESULTS: A total of 117 Italian SLE patients (M:F 13:104; mean age
      40.6 +/- 11.6 years, mean disease duration 127.5 +/- 94.1 months) were recruited
      into the study. The Italian version of the LupusQoL((c)) demonstrated substantial
      evidence of convergent validity in these patients when compared with equivalent
      items of the SF-36. In addition, the LupusQoL((c)) discriminated between patients
      with different degrees of disease activity as measured by the SLEDAI-2 K. SLE
      patients with higher disease activity (SLEDAI-2K >=4) showed poor QoL compared
      with those with lower disease activity (SLEDAI-2K <4), with significant
      differences in the domains of physical health, planning, burden to others and
      fatigue (p = 0.001, p = 0.04, p = 0.03, p = 0.04, respectively). The confirmatory
      factor analysis using the eight domain loadings of the 34 items showed a poor fit
      (chi(2)/degree of freedom (df) 2.26, chi(2 )= 1128.6 (p < 0.001), root mean
      square error of approximation (RMSEA) = 0.167; goodness-of-fit index (GFI) =
      0.606, comparative fit index (CFI) = 0.649)). Screeplot analysis suggested a five
      factor loading structure and confirmatory factor analysis result of which is
      similar to the eight-factor model. A good internal consistency was observed
      (Cronbach's alpha 0.89-0.91). Test-retest reliability was good to excellent
      between baseline and day 15 (intraclass correlation coefficient (ICC) 0.90-0.98).
      CONCLUSION: The Italian version of the LupusQoL((c)) is a valid tool for adult
      patients with SLE.

PMID- 24569394
TI  - The importance of implementing proper selection of excipients in lupus clinical
      trials.
AB  - Peptide therapeutics hold attractive potential. However, the proper stabilization
      of such therapeutics remains a major challenge. Some peptides are marginally
      stable and are prone to degradation. Therefore, in addition to chemical
      modifications that can be introduced in their sequence, a wide variety of
      excipients are added in the formulation to stabilize them, as is also done
      routinely for protein therapeutics. These substances are supposed to suppress
      peptide/protein aggregation and surface adsorption, facilitate their dispersion
      and additionally to provide physiological osmolality. Particular attention has to
      be paid to the choice of such excipients. Here we highlight the observation that
      in certain clinical situations, an excipient that is not totally inert can play a
      highly damaging role and mask (or even reverse) the beneficial effect of a
      molecule in clinical evaluation. This is the case, for instance, of trehalose, a
      normally safe excipient, which notably has proven to act as an activator of
      autophagy. This excipient, although used efficiently in several therapeutics,
      adversely impacted a phase IIb clinical trial for human and murine lupus, a
      systemic autoimmune disease in which it has been recently discovered that at the
      base line, autophagy is already abnormally enhanced in lymphocytes. Thus, in this
      particular pathology, while the peptide that was tested was active in lupus
      patients when formulated in mannitol, it was not efficient when formulated in
      trehalose. This observation is important, since autophagy is enhanced in a
      variety of pathological situations, such as obesity, diabetes, certain
      neurological diseases, and cancer.

PMID- 24569395
TI  - The emergence of systemic lupus erythematosus in hypothyroid patients: two case
      reports and mini review.
AB  - Systemic lupus erythematosus (SLE) is a multi-systemic autoimmune disease that
      involves almost all the organs in the human body and is characterized by auto
      antibodies formation. Autoimmune thyroid diseases (AITD) are organ-specific
      diseases that are associated with a production of a variety of antibodies such as
      antinuclear antibodies, anti-double-stranded DNA, anti-Ro antibodies, anti
      cardiolipin antibodies, and others. The diagnosis of AITD in patients with SLE is
      well known, but the reverse is rarely reported. We present two cases of
      adolescent girls in whom SLE evolved one year after being diagnosed with
      hypothyroidism. 

PMID- 24569396
TI  - Postural tachycardia syndrome (POTS) and other autonomic disorders in
      antiphospholipid (Hughes) syndrome (APS).
AB  - BACKGROUND: Antiphospholipid syndrome (APS) is an autoimmune hypercoagulable
      disorder that has been shown to cause a large number of cardiac and neurological
      manifestations. Two recent studies have demonstrated abnormalities in
      cardiovascular autonomic function testing in APS patients without other
      cardiovascular or autoimmune disease. However, an association between autonomic
      disorders such as postural tachycardia syndrome and APS has not previously been
      described. METHODS AND RESULTS: Data were obtained by retrospective chart review.
      We identified 15 patients who have been diagnosed with APS and an autonomic
      disorder. The median age of the patients at the time of data analysis was 39
      years. The autonomic disorders seen in these patients included postural
      tachycardia syndrome, neurocardiogenic syncope and orthostatic hypotension. The
      majority of patients (14/15) were female and the majority (14/15) had non
      thrombotic neurological manifestations of APS, most commonly migraine, memory
      loss and balance disorder. Many also had livedo reticularis (11/15) and Raynaud's
      phenomenon (nine of 15). In some patients, the autonomic manifestations improved
      with anticoagulation and/or anti-platelet therapy; in others they did not. Two
      patients with postural tachycardia syndrome who failed to improve with the usual
      treatment of APS have been treated with intravenous immunoglobulin with
      significant improvement in their autonomic symptoms. CONCLUSION: We believe that
      autonomic disorders in APS may represent an important clinical association with
      significant implications for treatment.

PMID- 24569398
TI  - Royal college calls for 11% of NHS budget to reach primary care by 2017.

PMID- 24569397
TI  - PCMdb: pancreatic cancer methylation database.
AB  - Pancreatic cancer is the fifth most aggressive malignancy and urgently requires
      new biomarkers to facilitate early detection. For providing impetus to the
      biomarker discovery, we have developed Pancreatic Cancer Methylation Database
      (PCMDB, http://crdd.osdd.net/raghava/pcmdb/), a comprehensive resource dedicated
      to methylation of genes in pancreatic cancer. Data was collected and compiled
      manually from published literature. PCMdb has 65907 entries for methylation
      status of 4342 unique genes. In PCMdb, data was compiled for both cancer cell
      lines (53565 entries for 88 cell lines) and cancer tissues (12342 entries for
      3078 tissue samples). Among these entries, 47.22% entries reported a high level
      of methylation for the corresponding genes while 10.87% entries reported low
      level of methylation. PCMdb covers five major subtypes of pancreatic cancer;
      however, most of the entries were compiled for adenocarcinomas (88.38%) and
      mucinous neoplasms (5.76%). A user-friendly interface has been developed for data
      browsing, searching and analysis. We anticipate that PCMdb will be helpful for
      pancreatic cancer biomarker discovery. 

PMID- 24569399
TI  - A fluorescent off-on NBD-probe for F(-) sensing: theoretical validation and
      experimental studies.
AB  - The design, synthesis and fluoride sensing ability of a 7-nitro-2,1,3
      benzoxadiazole (NBD) based chemodosimeter is reported. Theoretical calculations
      were used to design a more applicable off-on response, by choosing NBD as the
      accurate fluorophore. Reaction of the NBD-probe with 300 equivalents of
      tetrabutyl ammonium fluoride (TBAF) exhibited a response time of 80 minutes and
      the reaction was selective to F(-) and sensing of the ion was marked by a 110
      fold enhancement of green fluorescence. The off-on fluorescence characteristics
      of the probe enabled its application in live-cell imaging of intracellular F(-)
      ions.

PMID- 24569400
TI  - Computer-assisted reproductive surgery: microsurgery for the digital age.
AB  - Although considerable progress has been made in the field of medically assisted
      reproduction, minimally invasive surgery remains of vital importance in
      optimizing and preserving fertility, as well as treating infertility. By
      definition, reproductive surgery employs microsurgical techniques with the
      objective of restoring natural fertility or enhancing assisted reproductive
      technologies. The avant-garde minimalist philosophy of this branch of gynecology
      has made it the natural trailblazer of laparoscopic surgery. Minimally invasive
      conservative treatment of uterine, tubal, ovarian and peritoneal pathology has
      long been the gold standard for women of reproductive age and those seeking
      fertility preservation. Robust surgical outcome data acknowledge clear advantages
      of advanced laparoscopic surgery over laparotomy. However, this comes at the cost
      of significant technical challenges. Computer-assisted laparoscopy, also known as
      robotic surgery, is posed to address the practical limitations of conventional
      laparoscopic surgery and bridge this technical gap. This enabling technology is a
      conceptual fusion of the practicality of conventional open surgery and the
      minimally invasive nature of laparoscopic surgery. With this comes the promise of
      simplifying complex minimally invasive fertility-sparing procedures so that they
      can be performed in a safe and reproducible manner by reproductive specialists. 

PMID- 24569401
TI  - Minimally invasive hysterectomy for benign indications.
AB  - After Cesarean section, hysterectomy is one of the most common surgeries
      performed on women throughout the world utilized for the definitive management of
      common gynecologic conditions. Minimally invasive surgical techniques offer many
      advantages for the patient including decreased scarring, better cosmesis,
      decreased pain, short hospital stay, and a faster return to normal activities
      overall decreasing the morbidity of this surgery on our patients. The original
      minimally invasive hysterectomy was vaginal hysterectomy. With the advent of
      laparoscopic surgical techniques and increasing technology minimally invasive
      hysterectomy methods have evolved over time, in order to try to increase the
      candidacy for minimally invasive hysterectomy methods and avoid laparotomy. This
      paper will review minimally invasive surgical methods of hysterectomy including
      the currently available tools and techniques. Advantages and disadvantages of
      each approach will be discussed. Guidelines for the evaluation of patients and
      criterion that should be utilized in choosing the appropriate surgical approach
      for each patient will also be outlined. 

PMID- 24569402
TI  - Vaginal hysterectomy: the original minimally invasive surgery.
AB  - Hysterectomy is one of the most commonly performed procedures in the United
      States. It is a unique procedure with multiple routes of access and multiple
      operative techniques. While focus has shifted towards minimally invasive
      techniques, the vaginal hysterectomy should be ranked first in this category, as
      it represents an original natural orifice surgery. Vaginal hysterectomy offers
      the least invasive approach to hysterectomy, with the lowest associated risks and
      costs. Despite these benefits, vaginal hysterectomy has experienced a decline in
      the last two decades. This decline is likely due to both the prevalence of
      fibroid uterus as a major indication for hysterectomy, and the decline of vaginal
      surgical skills among gynecologic surgeon due to more recent focus on
      laparoscopic proficiency. While vaginal hysterectomy is not risk-free, and is not
      the best option for all diagnoses, it should be given first-line consideration
      when planning to perform a benign hysterectomy. The purpose of this review is to
      understand the origins and evolution of the vaginal hysterectomy, the evidence
      based benefits of this route of surgery, and best practice methods to ensure that
      patients receive safe and effective surgical treatment. 

PMID- 24569403
TI  - Myomectomy: technique and current indications.
AB  - Uterine fibroids are the commonest benign tumor of the female genital tract. They
      affect a significant proportion of reproductive aged women and while some women
      are asymptomatic, fibroids can cause excessive menstrual bleeding, pelvic
      pressure, and adversely affect reproductive outcomes. Myomectomy is the most
      suitable surgical option for women who desire preservation of their fertility
      potential. However, only a selected group of women of childbearing age will
      benefit from a myomectomy. Furthermore, the consequences of myomectomy on
      reproductive function have remained controversial. The purpose of this paper is
      to review the main surgical approaches for myomectomy - hysteroscopic resection,
      laparoscopic myomectomy and open myomectomy (by laparotomy) - and discuss
      evidence-based indications for myomectomy in women with fibroids, especially with
      regards to its impact on reproductive outcomes. A critical review of the
      literature pertaining to the surgical approaches of myomectomy and the
      indications for myomectomy was performed, focusing on their impact on fertility
      and reproductive outcomes. Myomectomy is useful for the treatment of symptomatic
      fibroids and in selected women with infertility. Symptomatic submucosal fibroids
      are classically treated by hysteroscopic resection. Symptomatic intramural and
      subserosal fibroids may be treated by myomectomy, either by laparotomy or
      laparoscopy depending on their number and size. Prophylactic myomectomy is not
      recommended for preventing obstetrical complications or the risk of
      leiomyosarcoma. Although fibroids can have a negative effect on fertility, only
      the removal of submucosal fibroids has been consistently shown to improve
      spontaneous fertility or outcomes of assisted reproduction technology. 

PMID- 24569404
TI  - Minimally invasive approach to pelvic organ prolapse: a review.
AB  - Uterovaginal prolapse, vaginal vault prolapse, and rectal prolapse are pelvic
      floor support problems that have been traditionally addressed through abdominal,
      vaginal or perineal approaches. Over the past decade, minimally invasive
      approaches to these procedures have been reported and refined. We discuss both
      laparoscopic and robotic techniques for repair of uterovaginal prolapse, vaginal
      vault prolapse, and rectal prolapse. In addition, we summarize currently
      available success and complication data associated with each technique. 

PMID- 24569405
TI  - Post-traumatic amenorrhea: the role of diagnostic and operative hysteroscopy in
      the prevention, diagnosis, differential diagnosis and treatment.
AB  - AIM: The aim of the study was to evaluate the clinical usefulness of the
      selective removal of residual intrauterine trophoblastic tissue by using a
      hysteroscopic procedure, especially in the prevention of the Intra-Uterine
      Adhesion's Syndrome. METHODS: Seventy-six patients had an Asherman's Syndrome: 5
      cases after laparotomic myomectomy, 1 after caesarean section, 2 after
      hysteroscopic myomectomy, 10 after VIP, 1 with a severe vaginal endometriosis, 1
      after conisation, 4 after a post-partum hemorrhage due to coagulopathy or uterine
      atony, 20 cases after D&C because of PPH due to placental retention, 26 after
      repetitive D&Cs because of AUB due to post abortion chorial residues' retention,
      6 cases after D&C for post menopausal AUB. Thirty-six patients presented AUB due
      to chorioplacental residues retention: 14 cases after a vaginal delivery or a
      caesarean section, 4 after VIP, 18 cases after repetitive D&Cs for incomplete or
      internal spontaneous abortion. Complete physical examination, transvaginal
      ultrasonography and operative hysteroscopy was offered as first treatment to all
      patients. Surgical treatment of IUA depends on the type (I-IV) and is based on
      the section of synechiae, liberation of the uterine cavity and tubal recesses,
      recovery of the residual endometrium to restore the physiology of the
      reproductive tract. Our technique to remove the chorioplacental residues is based
      on: correct use of loops and electric currents, enucleation by cold loops of the
      base of the placental implant, and to single out the level of miometrial
      infiltration. RESULTS: After treatment we have noticed: two hysterectomies (for
      persistent AUB after myomectomy and for severe bleeding after dehiscence of a C.
      section), restoration of regular menstruations in 94.6% of patients (6 women in
      menopause), disappearance of pelvic pain and dysmenorrhea in all cases (100%), 8
      pregnancies of the 9 women who were wanting child after hysteroscopic
      synechiolysis (88.9%). CONCLUSION: According to the present study, the best way
      to prevent IUA is to make D&C for abortion, avoiding waiting longer than 24
      hours, perform a D&C and then a diagnostic hysteroscopy after PPH in symptomatic
      women, reserve D&Cs only for a PPH, or an incomplete abortion, limit to only one
      D&C, always make a diagnostic hysteroscopy after D&C and uterine plugging for
      PPH.

PMID- 24569406
TI  - Pycnogenol(r) in postpartum symptomatic hemorrhoids.
AB  - AIM: The aim of this registry study was to evaluate the efficacy of Pycnogenol(r)
      (Horphag Research Ltd.), a standardized extract from the French maritime pine
      bark, to control signs/symptoms and prevent complications associated with
      hemorrhoids in the months after delivery in healthy women. METHODS: Women with
      hemorrhoids after their second pregnancy were included within the third month
      after pregnancy. Pycnogenol dosage was 150 mg/day for 6 months. Symptoms for 4th
      and 3rd degree hemorrhoids were evaluated. RESULTS: The registry groups were
      comparable. For 4th degree hemorrhoids, main symptoms were reduced after 6 months
      in all patients, but the group using Pycnogenol in addition to standard best
      management showed more improvement. In patients with 3rd degree hemorrhoids,
      symptoms were reduced in both management groups at 6 months; with Pycnogenol the
      reduction in symptoms scores was significantly better. At 6 months 18/24 subjects
      (75%) in the Pycnogenol group were symptom-free in comparison with 14/25 (56%) in
      controls. In the 4th degree hemorrhoid group, 7/10 patients (70%) in the
      Pycnogenol group were symptom-free at 6 months in comparison with 4/11 subjects
      (36%) in the best management group. No significant side effects were observed.
      CONCLUSION: Pycnogenol appears to positively affect hemorrhoid signs and symptoms
      in the months after pregnancy.

PMID- 24569407
TI  - Effect of metformin on the level of anti-Mullerian hormone in therapy of
      polycystic ovary syndrome in obese women.
AB  - AIM: Anti-Mullerian hormone (AMG) reduction in women with hyperinsulinemia in
      therapy with metformin suggests that metformin affects the level of AMH and
      ovulatory dysfunction through insulin-mediated mechanisms. Aim of the study was
      to assess the effects of metformin hydrochloride (Siofor) on the level of AMH in
      women with polycystic ovary syndrome and obesity. METHODS: The study involved 40
      women with PCOS, aged 22 to 35 years (mean age 28.7+/-5.2 years) with body mass
      index (BMI) 32.5+/-4.3 kg/m2. All patients received metformin hydrochloride
      (Siofor) orally, 1 tablet (850 mg) two times a day for six months. After three
      and six months of therapy anthropometric characteristics, concentration of
      hormones in the blood serum were assessed. RESULTS: In patients receiving Siofor
      a decrease of BMI, waist-hip ratio (P<0.05), concentration of T, as well as free
      androgen index (FAI) (P<0.01) was shown. Furthermore, there was a decrease in
      ovarian volume by 12%. AMH concentration during therapy did not changed
      significantly. CONCLUSION: The hypothesis that a decline in AMG level is a
      consequence of the reduced BMI, which was significant in the group of women with
      hyperinsulinemia, does not seem convincing in view of the fact that patients with
      a normal insulin level also showed a trend to lower BMI, which, however, was not
      accompanied by a decrease in its concentration.

PMID- 24569408
TI  - [Pharmacological, metabolic and clinical aspects of new oral contraceptive
      associations containing natural estrogens].
AB  - Introduction of new compounds containing natural estrogens represented a major
      development in the field of hormonal contraception. Micronized estradiol (E2) and
      its estere valerate (EV), is more easily metabolized by the liver than
      ethynylestradiol (EE). This causes minimal metabolic impact, but the weak
      estrogenic activity needs not be antagonized by androgenic progestin and requires
      progestin capable to stabilize the endometrium. Dienogest (DNG), an
      antiandrogenic progestin with a short half-life, is associated with estradiol
      valerate (EV) in a quadriphasic fashion. In comparison to EE/levonorgestrel
      (LNG), EV/DNG is more neutral on metabolism and coagulation. Furthermore, it does
      not seem to negatively affect the cardiovascular system and breast. Cycle control
      is optimal with a higher prevalence of amenorrhea and reduction of menstrual
      flow. For this reason EV/DNG can be tehrapeutic for heavy menstrual bleedings.
      Nomegestrol acetate (NOMAc), an anti-andogen progestin with a long half-life is
      combined in monophasic regimen with micronized E2. E2/NOMAc is more neutral than
      EE/LNG on metabolism and more neutral than EE/DRSP on coagulation. NOMAc reduces
      peripheral tissue estrogen formation, and this may be beneficial for the breast.
      The two formulations exert a high contraceptive efficacy similar to the ones
      containing EE, but with less estrogen-related side-effects. The additional
      benefits due to DNG and NOMAc need to be further explored. 

PMID- 24569409
TI  - Hypertension in pregnancy: the most recent findings in pathophysiology, diagnosis
      and therapy.
AB  - Hypertension in pregnancy is a major cause of maternal, fetal and neonatal
      morbidity and mortality, both in developing and developed countries. That is
      because it is the most common pathological condition during pregnancy and its
      development is associated with high risk of severe complications: mother could be
      affected by placental abruption, cerebrovascular events, organ dysfunction and
      could develop disseminated intravascular coagulation, instead the foetus could be
      affected by intrauterine growth retardation, premature birth and intrauterine
      death. Aware that preeclampsia still remains an enigma for different aspects,
      this review aims to provide a comprehensive update of all the current literature
      regarding this disease. In particular, the main purpose of this review is to
      emphasize the most recent findings about the pathophysiology, diagnosis and
      submit a revision of the most recent guidelines in relation to drug therapy, with
      particular attention to the evaluation of risks and benefits associated with the
      use of various classes of the currently available drugs. 

PMID- 24569410
TI  - Prenatal diagnosis and surveillance of a true umbilical knot by two- and three
      dimensional ultrasonography.

PMID- 24569411
TI  - [The levonogestrel-releasing intrauterine device and endometrial cancer: a
      potential opportunity for young women].

PMID- 24569412
TI  - How essential is synchronization in achieving successful embryo implantation?

PMID- 24569414
TI  - Serum uric acid levels are associated with high blood pressure in Chinese
      children and adolescents aged 10-15 years.
AB  - OBJECTIVE: The present study examined the association between uric acid levels
      and high blood pressure in a multiethnic study of Chinese children and
      adolescents. METHODS: The participants were divided into four different groups
      according to the uric acid quartiles. Three logistic regression models were
      conducted to investigate the relationship between the high blood pressure and
      uric acid levels. Model 1 adjusted age, sex and ethnicity. Model 2 adjusted age,
      sex, ethnicity, total cholesterol, high-density lipoprotein, low-density
      lipoprotein, triglycerides, estimated glomerular filtration rate, fasting glucose
      and waist circumference. Model 3 adjusted all the confounding factors in model 2
      except the waist circumference and BMI. The concentrations of uric acid in high
      blood pressure participants and normotensive participants were compared with or
      without adjustment for confounding factors. RESULTS: A total of 3778 participants
      aged 10-15 years from the Xinjiang Congenital Heart Disease Survey were included
      in the present study. The percentages of the high blood pressure in the four
      different uric acid quartiles were 7.4, 8.6, 9.6 and 11.8%, respectively. In
      model 1, 2 and 3 of the logistic regression, the participants in the third and
      fourth uric acid quartiles had significantly higher chance of suffering the high
      blood pressure when compared with the participants in the first uric acid
      quartile [odds ratio 1.608, 1.587, 1.597, P = 0.005, 0.015, 0.015, respectively,
      between participants in the first quartile and the third quartile; odds ratio
      1.981, 1.945, 1.810, P = 0.001, 0.002, 0.007, respectively, between participants
      in the first quartile and the fourth quartile). The concentrations of serum uric
      acid were 220.7 MUmol/l in high blood pressure participants and 204.1 MUmol/l in
      normotensive participants (P = 0.024). After adjustment for confounding factors,
      the concentrations of serum uric acid were 219.7 vs. 204.5 MUmol/l in one model
      (P < 0.001) and 219.3 vs. 204.5 MUmol/l in the other model (P < 0.001).
      CONCLUSIONS: Among Chinese children and adolescents, increasing levels of serum
      uric acid are associated with high blood pressure.

PMID- 24569413
TI  - Do other cardiovascular risk factors influence the impact of age on the
      association between blood pressure and mortality? The MORGAM Project.
AB  - OBJECTIVE: To investigate age-related shifts in the relative importance of SBP
      and DBP as predictors of cardiovascular mortality and all-cause mortality and
      whether these relations are influenced by other cardiovascular risk factors.
      METHODS: Using 42 cohorts from the MORGAM Project with baseline between 1982 and
      1997, 85 772 apparently healthy Europeans and Australians aged 19-78 years were
      included. During 13.3 years of follow-up, 9.2% died (of whom 7.2% died due to
      stroke and 21.1% due to coronary heart disease, CHD). RESULTS: Mortality risk was
      analyzed using hazard ratios per 10-mmHg/5-mmHg increase in SBP/DBP by
      multivariate-adjusted Cox regressions, including SBP and DBP simultaneously.
      Because of nonlinearity, SBP and DBP were analyzed separately for blood pressure
      (BP) values above and below a cut-point wherein mortality risk was the lowest.
      For the total population, significantly positive associations were found between
      stroke mortality and SBP [hazard ratio = 1.19 (1.13-1.25)] and DBP at least 78
      mmHg [hazard ratio = 1.08 (1.02-1.14)], CHD mortality and SBP at least 116 mmHg
      [1.20 (1.16-1.24)], and all-cause mortality and SBP at least 120 mmHg [1.09 (1.08
      1.11)] and DBP at least 82 mmHg [1.03 (1.02-1.05)]. BP values below the cut
      points were inversely related to mortality risk. Taking into account the age * BP
      interaction, there was a gradual shift from DBP (19-26 years) to both DBP and SBP
      (27-62 years) and to SBP (63-78 years) as risk factors for stroke mortality and
      all-cause mortality, but not CHD mortality. The age at which the importance of
      SBP exceeded DBP was for stroke mortality influenced by sex, cholesterol, and
      country risk. CONCLUSION: Age-related shifts to the superiority of SBP exist for
      stroke mortality and all-cause mortality, and for stroke mortality was this shift
      influenced by other cardiovascular risk factors.

PMID- 24569417
TI  - Medication persistence and the use of generic and brand-name blood pressure
      lowering agents.
AB  - BACKGROUND: Because of their lower cost, healthcare systems recommend physicians
      to prefer generic products, rather than brand-name medicaments. There is then
      considerable interest and debate concerning safety and effectiveness of generic
      products. Few studies have compared patients treated with brand-name and generic
      drugs for adherence to treatment, with somewhat inconsistent results. The primary
      objective of this study was to compare the risk of discontinuing antihypertensive
      drug therapy in patients treated with generic or brand-name agents. METHODS: The
      101,618 beneficiaries of the Healthcare system of Lombardy, Italy, aged 18 years
      or older who were newly treated on monotherapy with antihypertensive generic or
      brand-name drugs during 2008, were followed until the earliest date among those
      of the occurrence of treatment discontinuation to whatever antihypertensive drug
      therapy (outcome), or censoring (death, emigration, 12 months after treatment
      initiation). Hazard ratios of discontinuation associated with starting on generic
      or brand-name products (intention-to-treat analysis), and incidence rate ratio of
      discontinuation during periods on generic and brand-name products (as-treated
      analysis) were respectively estimated from a cohort and self-controlled case
      series analyses. RESULTS: Patients who started on generics did not experience a
      different risk of discontinuation compared with those starting on brand-name
      agents (hazard ratio: 1.00; 95% confidence interval 0.98-1.02). Discontinuation
      did not occur with different rates during periods covered by generics or brand
      name agents (incidence rate ratio: 1.01; 95% confidence interval 0.96-1.11)
      within the same individuals. A number of sensitivity and subgroup analyses
      confirmed the robustness of these findings. CONCLUSION: Generic products are not
      responsible for the high rate of discontinuation from antihypertensive drug
      therapy. Assuming therapeutic equivalence, clinical implication is of prescribing
      generic drug therapies.

PMID- 24569415
TI  - Dietary fish oil improves endothelial function and lowers blood pressure via
      suppression of sphingolipid-mediated contractions in spontaneously hypertensive
      rats.
AB  - OBJECTIVE: Long-chain n-3 polyunsaturated fatty acids from oily fish reduce blood
      pressure (BP) in hypertension. Previously, we demonstrated that hypertension is
      associated with marked alterations in sphingolipid biology and elevated ceramide
      induced vasoconstriction. Here we investigated in spontaneously hypertensive rats
      (SHRs) whether fish oil improves endothelial function including reduced vascular
      contraction induced via the sphingolipid cascade, resulting in reduced BP.
      METHODS: Twelve-week-old SHRs were fed a control or fish oil-enriched diet during
      12 weeks, and BP was recorded. Plasma sphingolipid levels were quantified by mass
      spectrometry and the response of isolated carotid arteries towards different
      stimuli was measured. Furthermore, erythrocyte membrane fatty acid composition,
      thromboxane A2 formation and cytokine secretion in ex-vivo lipopolysaccharide
      stimulated thoracic aorta segments were determined. RESULTS: The fish oil diet
      reduced the mean arterial BP (P < 0.001) and improved endothelial function, as
      indicated by a substantially increased relaxation potential towards ex-vivo
      methacholine exposure of the carotid arteries (P < 0.001). The long-chain n-3
      polyunsaturated fatty acid diet resulted in altered levels of specific
      (glucosyl)ceramide subspecies (P < 0.05), reduced membrane arachidonic acid
      content (P < 0.001) and decreased thromboxane concentrations in plasma (P <
      0.01). Concomitantly, the fish oil diet largely reduced ceramide-induced
      contractions (P < 0.01), which are predominantly mediated by thromboxane.
      Furthermore, thromboxane A2 and interleukin-10 were reduced in supernatants of
      lipopolysaccharide-stimulated thoracic aorta of SHRs fed the fish oil diet while
      RANTES (regulated on activation, normal T-cell expressed and secreted) was
      enhanced. This may contribute to reduced vasoconstriction in vivo. CONCLUSIONS:
      Dietary fish oil lowers BP in SHRs and improves endothelial function in
      association with suppression of sphingolipid-dependent vascular contraction.

PMID- 24569416
TI  - The role of body weight, fat distribution and weight change in ethnic differences
      in the 9-year incidence of hypertension.
AB  - OBJECTIVE: To investigate the role of body composition (body weight, fat
      distribution and weight change over time) in ethnic differences in the incidence
      of hypertension in an ethnic Dutch, South Asian Surinamese and African Surinamese
      background population living in the Netherlands. METHODS: We included 361
      participants without hypertension at baseline (147 ethnic Dutch, 82 South Asian
      Surinamese, 132 African Surinamese), aged 35-60 years, in whom anthropometric
      measurements and blood pressures were measured at baseline and after mean 9 years
      of follow-up. Data were analysed using logistic regression analyses, with
      hypertension at follow up as a dependent variable. RESULTS: Body weight, fat
      distribution and weight gain were positively associated with the risk of
      developing hypertension; these associations did not statistically significantly
      differ between ethnic groups [odds ratios (ORs), 95% confidence interval (95% CI)
      per SD: BMI 1.5 (1.2-2.0); waist circumference 1.5 (1.2-1.9); waist to hip ratio
      (WHR) 1.4 (1.1-1.9), weight gain of 1-2.9 kg/m 1.8 (0.9-3.8)]. As compared with
      Dutch, a higher incidence of hypertension was found among South Asian Surinamese
      [OR 2.6 (1.4-4.8)] and in particular among African Surinamese [OR 3.1 (1.76
      5.30)]. Among South Asian Surinamese, adjustment for WHR attenuated the OR the
      most [OR 1.9 (1.0-3.7)]; among African Surinamese, the strongest effect was
      observed for adjustment by BMI and WHR simultaneously [OR 2.5 (1.4-4.4)].
      CONCLUSION: The ethnic differences in the incidence of hypertension among a
      middle-aged group with a Dutch, South Asian Surinamese and African Surinamese
      background were partly explained by body composition. This suggests that other
      factors may be involved, including genetic factors or unidentified other
      determinants.

PMID- 24569418
TI  - Large artery stiffness and carotid flow pulsatility in stroke survivors.
AB  - OBJECTIVE: Aortic stiffness is increased in lacunar stroke. The precise mechanism
      linking aortic stiffness to symptomatic lacunar stroke is not well understood.
      The aim of this study was to compare the effects of aortic stiffness, carotid
      stiffness, central blood pressure, and cerebrovascular resistance on carotid flow
      pulsatility according to stroke subtype. METHODS: Two hundred and one consecutive
      patients were examined 13 months after hospitalization for their first-ever
      ischemic stroke. The stroke subtype was classified using the Causative
      Classification of Stroke System. Carotid-femoral pulse wave velocity (PWV) was
      used as a measure of aortic stiffness. Common carotid flow pulsatility was
      expressed as resistive index. Central blood pressure was measured using
      applanation tonometry. RESULTS: Complete data were available for 174 patients
      (mean age... 67 +/- 10 years, 64% men). In patients with lacunar stroke, aortic
      PWV was higher (13.11 +/- 2.74 m/s) than in individuals with large artery
      atherosclerosis (9.98 +/- 1.87 m/s, P <0.001), cardioembolic (11.31 +/- 3.18 m/s,
      P = 0.04) or cryptogenic stroke (11.13 +/- 3.2 m/s, P = 0.01). Similarly, central
      SBP and resistive index were higher in patients with lacunar stroke (145 +/- 23
      mmHg and 0.80 +/- 0.04, respectively) than those with large artery
      atherosclerosis (128 +/- 18 mmHg, P <0.01 and 0.74 +/- 0.07, P <0.01,
      respectively) or cryptogenic stroke (132 +/- 18 mmHg, P <0.01 and 0.76 +/- 0.07,
      P <0.05, respectively). In multivariate analysis, aortic stiffness and central
      pulse pressure were the main determinants of resistive index independent of
      stroke subtype. CONCLUSION: Our results suggest that aortic stiffening, by
      reducing the buffering function of the aorta and thereby increasing the
      transmission of pressure and flow pulsatility into the cerebral arterioles, may
      contribute to the pathogenesis of lacunar stroke.

PMID- 24569420
TI  - Validation and comparison of three formulae to estimate sodium and potassium
      excretion from a single morning fasting urine compared to 24-h measures in 11
      countries.
AB  - BACKGROUND AND OBJECTIVES: Although 24-h urinary measure to estimate sodium and
      potassium excretion is the gold standard, it is not practical for large studies.
      We compared estimates of 24-h sodium and potassium excretion from a single
      morning fasting urine (MFU) using three different formulae in healthy
      individuals. METHODS: We studied 1083 individuals aged 35-70 years from the
      general population in 11 countries. A 24-h urine and MFU specimen were obtained
      from each individual. A subset of 448 individuals repeated the measures after 30
      90 days. The Kawasaki, Tanaka, and INTERSALT formulae were used to estimate
      urinary excretion from a MFU specimen. RESULTS: The intraclass correlation
      coefficient (ICC) between estimated and measured sodium excretion was higher with
      Kawasaki (0.71; 95% confidence interval, CI: 0.65-0.76) compared with INTERSALT
      (0.49; 95% CI: 0.29-0.62) and Tanaka (0.54; 95% CI: 0.42-0.62) formulae (P
      <0.001). For potassium, the ICC was higher with the Kawasaki (0.55; 95% CI: 0.31
      0.69) than the Tanaka (0.36; 95% CI: -0.07 to 0.60; P <0.05) formula (no
      INTERSALT formula exists for potassium). The degree of bias (vs. the 24-h urine)
      for sodium was smaller with Kawasaki (+313 mg/day; 95% CI: +182 to +444) compared
      with INTERSALT (-872 mg/day; 95% CI: -728 to -1016) and Tanaka (-548 mg/day; 95%
      CI: -408 to -688) formulae (P <0.001 and P = 0.02, respectively). Similarly for
      potassium, the Kawasaki formula provided the best agreement and least bias. Blood
      pressure correlated most closely and similarly with the 24-h and Kawasaki
      estimates for sodium compared with the other two formulae. CONCLUSION: In a
      diverse population, the Kawasaki formula is the most valid and least biased
      method of estimating 24-h sodium excretion from a single MFU and is suitable for
      population studies.

PMID- 24569419
TI  - Genetic variants in nicotinic acetylcholine receptor genes jointly contribute to
      kidney function in American Indians: the Strong Heart Family Study.
AB  - BACKGROUND: Cigarette smoking negatively affects kidney function. Genetic
      variants in the nicotinic acetylcholine receptor (nAChR) genes have been
      associated with nicotine dependence, and are likely to influence renal function
      and related traits. Whereas each single variant may only exert a small effect,
      the joint contribution of multiple variants to the risk of disease could be
      substantial. METHODS: Using a gene-family approach, we investigated the joint
      association of 61 tagging SNPs in seven genes encoding the nAChRs with kidney
      function in 3620 American Indians participating in the Strong Heart Family Study,
      independent of known risk factors. Kidney function was evaluated by estimated
      glomerular filtration rate, urinary albumin/creatinine ratio, albuminuria and
      chronic kidney disease. The joint impact of smoking-related variants was assessed
      using the weighted truncated product method. RESULTS: Multiple SNPs showed
      marginal individual effect on renal function variability, and only a few survive
      multiple comparison correction. In contrast, a gene-family analysis considering
      the joint impact of all 61 SNPs reveals significant associations of the nAChR
      gene family with kidney function variables including estimated glomerular
      filtration rate, urinary albumin/creatinine ratio, and albuminuria (all Ps <=
      0.0001) after adjusting for established risk factors including cigarette smoking.
      CONCLUSION: Genetic variants in nAChR genes jointly contribute to renal function
      or kidney damage in American Indians. The effects of these genetic variants on
      kidney function or damage are independent of traditional risk factors including
      cigarette smoking per se.

PMID- 24569422
TI  - Lift-and-fill face lift: integrating the fat compartments.
AB  - BACKGROUND: Recent discovery of the numerous fat compartments of the face has
      improved our ability to more precisely restore facial volume while rejuvenating
      it through differential superficial musculoaponeurotic system treatment.
      Incorporation of selective fat compartment volume restoration along with
      superficial musculoaponeurotic system manipulation allows for improved control in
      recontouring while addressing one of the key problems in facial aging, namely,
      volume deflation. This theory was evaluated by assessing the contour changes from
      simultaneous face "lifting" and "filling" through fat compartment-guided facial
      fat transfer. METHODS: A review of 100 face-lift patients was performed. All
      patients had an individualized component face lift with fat grafting to the
      nasolabial fold, deep malar, and high/lateral malar fat compartment locations.
      Photographic analysis using a computer program was conducted on oblique facial
      views preoperatively and postoperatively, to obtain the most projected malar
      contour point. Two independent observers visually evaluated the malar prominence
      and nasolabial fold improvements based on standardized photographs. RESULTS:
      Nasolabial fold improved by at least one grade in 81 percent and by over one
      grade in 11 percent. Malar prominence average projection increase was 13.47
      percent and the average amount of lift was 12.24 percent. The malar prominence
      score improved by at least one grade in 62 percent of the patients
      postoperatively, and 9 percent had a greater than one grade improvement. Twenty
      eight percent of the patients had a convex malar prominence postoperatively
      compared with 6 percent preoperatively. Malar prominence improved by at least one
      grade in 63 percent and by over one grade in 10 percent. CONCLUSIONS: The lift
      and-fill face lift merges two key concepts in facial rejuvenation: (1) effective
      tissue manipulation by means of lifting and tightening in differential vectors
      according to original facial asymmetry and shape; and (2) selective fat
      compartment filling of deep malar and high malar locations and nasolabial fold
      fat grafting to precisely control facial contouring. This was shown with
      objective numerical grading and through observer assessment. CLINICAL
      QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

PMID- 24569421
TI  - Microvascular modifications to optimize the transverse upper gracilis flap for
      breast reconstruction.
AB  - BACKGROUND: The free transverse upper gracilis flap is well described for breast
      reconstruction and is the authors' second choice. Medial thigh soft tissue
      creates a durable, pliable, aesthetic breast; however, it has been criticized for
      modest volume and short pedicle. This demands frequent use of bilateral flaps for
      unilateral reconstructions, sacrifice of thoracodorsal vessels, and/or use of
      vein grafts. The authors have overcome these issues by modifying their
      microvascular techniques. METHODS: The authors describe several maneuvers that
      they have introduced, including excision and replacement of costal cartilage,
      using nontraditional internal mammary arterial anastomoses, and using adductor
      branches for flap-to-flap anastomoses to allow double flap reconstructions. The
      authors describe their case series of 30 transverse upper gracilis flaps to
      reconstruct 20 breasts in 18 patients. RESULTS: All flaps have survived. Seventy
      five percent of the reconstructions were unilateral, although of these, 67
      percent used two flaps to reconstruct one breast. The mean reconstructed breast
      was 360.9 g. Of 10 breasts reconstructed with double flaps, six used available
      adductor branches, whereas the others used internal mammary perforators, end-to
      side anastomoses, or retrograde arterial flow. To complement this clinical
      approach, an anatomical study of the branching patterns from the gracilis pedicle
      has been carried out on 33 cadaveric specimens. CONCLUSIONS: The authors' study
      has allowed a new classification system to be defined and demonstrates suitable
      branching patterns to allow flap-to-flap anastomoses in 75 percent of patients;
      in those 25 percent where this is not possible, alternative strategies for double
      flaps can be sought and have been used successfully in our clinical series.
      CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

PMID- 24569423
TI  - Hydrogen peroxide priming of the venous architecture: a new technique that
      reveals the underlying anatomical basis for venous complications of DIEP, TRAM,
      and other abdominal flaps.
AB  - BACKGROUND: Previous studies of venous anatomy lack the detail of their arterial
      counterparts because of (1) the technical challenge of retrograde perfusion
      against competent valves and (2) anterograde venous perfusion failing to
      adequately delineate the area of interest. We introduced a novel technique:
      retrograde hydrogen peroxide priming that dilates veins and renders valves
      incompetent, thereby facilitating complete cadaveric venous perfusion. METHODS:
      The superficial and deep venous systems of 41 hemiabdomens and 20 hemichests of
      unembalmed human cadavers were primed by retrograde injection with 6% hydrogen
      peroxide. Specimens were then injected with lead oxide contrast, radiographed,
      and dissected. In five hemiabdomens, the valves were mapped by dissection.
      Results were compared with archival venous studies of six total body injections,
      six abdominal lipectomy specimens, and two intraoperative venograms of delayed
      transverse rectus abdominis musculocutaneous flaps. RESULTS: Unprecedented venous
      filling of the anterior torso was demonstrated. Two types of superficial-to-deep
      venous connections were defined: large venae communicantes and small venae
      comitantes. Venae communicantes (>2 mm) formed major connections between large
      superficial and deep veins, mostly within 5 cm of the umbilicus in the abdomen,
      the axilla and fifth or sixth intercostal space parasternally. Seventy-four
      percent of venae communicantes coursed with arteries greater than 1.0 mm. Four
      major longitudinal valved subcutaneous pathways of the superficial inferior
      epigastric vein and superficial circumflex iliac vein were defined bilaterally
      with large avalvular transverse connections in the midline and small-caliber
      connections laterally that explain venous complications seen sometimes in
      transverse abdominal flaps. CONCLUSION: Retrograde hydrogen peroxide priming of
      veins in cadavers renders valves incompetent and facilitates detailed venous
      studies that help refine flap design and explain venous complications.

PMID- 24569424
TI  - Health-related quality of life in patients undergoing palmar fasciectomy for
      Dupuytren's disease.
AB  - BACKGROUND: The present study was undertaken to assess the health-related quality
      of life in patients with Dupuytren's disease who undergo palmar fasciectomy.
      METHODS: A prospective cohort of patients with Dupuytren's disease undergoing
      palmar and/or digital fasciectomy was recruited from the practice of three
      plastic surgeons in Hamilton, Ontario, Canada. After written informed consent was
      obtained, participants were asked to complete three health-related quality-of
      life questionnaires (i.e., Short Form-36, Michigan Hand Outcomes Questionnaire,
      and Health Utility Index Mark 3) at five time points: at 1 week and 1 day
      preoperatively, and at 1, 3, 6, and 12 months postoperatively. Ranges of motion
      and grip strength measurement were also recorded. RESULTS: For the 26 patients in
      the study, the multiattribute scores of the Health Utility Index Mark 3 improved
      from 0.80 before surgery to 0.83 at 12 months postoperatively (p > 0.05). There
      was no difference in the Short Form-36 scores, but the Michigan Hand Outcomes
      Questionnaire scores improved from 74 at 1 week preoperatively to 90 at the 12
      month postoperative visit (p < 0.001). CONCLUSIONS: Patients who undergo palmar
      fasciectomy for Dupuytren's disease experience a substantial improvement in their
      health-related quality of life 12 months after surgery. In the authors' study
      population, a benefit of 0.85 quality-adjusted life-year within 12 months was
      observed. This can be translated as follows: the average patient who undergoes
      palmar fasciectomy gains the equivalent of approximately 14.4 days (0.48 months)
      in perfect health by undergoing palmar fasciectomy. CLINICAL QUESTION/LEVEL OF
      EVIDENCE: Therapeutic, IV.

PMID- 24569425
TI  - The surgical correction of Pierre Robin sequence: mandibular distraction
      osteogenesis versus tongue-lip adhesion.
AB  - BACKGROUND: The authors present an outcomes analysis of mandibular distraction
      osteogenesis versus tongue-lip adhesion in the surgical treatment of Pierre Robin
      sequence. METHODS: A retrospective, 15-year, single-surgeon review was undertaken
      of all nonsyndromic neonates with Pierre Robin sequence treated with mandibular
      distraction osteogenesis (2004 to 2009; n = 24) or tongue-lip adhesion (1994 to
      2004; n = 15). Outcomes included time of extubation, length of intensive care
      unit stay, incidence of tracheostomy, and surgical complications. Polysomnography
      data were collected 1 month and 1 year postoperatively. Sleep study data included
      changes in oxygen saturation and apnea-hypopnea index. RESULTS: There were no
      postprocedure tracheostomies in the mandibular distraction osteogenesis group and
      four tracheostomies in the tongue-lip adhesion group. The preoperative oxygen
      saturations were significantly lower in the mandibular distraction osteogenesis
      group compared with tongue-lip adhesion (76.5 percent versus 82 percent; p <
      0.05). Preoperative apnea-hypopnea index was significantly higher in the
      mandibular distraction osteogenesis group compared with the tongue-lip adhesion
      group (47 versus 37.6; p < 0.05). Despite these preoperative differences,
      patients undergoing mandibular distraction osteogenesis demonstrated
      significantly higher oxygen saturation levels at 1 month (98.3 percent versus
      87.5 percent; p < 0.05) and 1 year postoperatively (98.5 percent versus 89.2
      percent; p < 0.05) and lower apnea-hypopnea index at 1 month (10.9 versus 21.6; p
      < 0.05) and 1 year postoperatively (2.5 versus 22.1; p < 0.05) compared with
      tongue-lip adhesion. Surgical complications were comparable between the two
      groups. CONCLUSIONS: In nonsyndromic patients with Pierre Robin sequence,
      mandibular distraction osteogenesis demonstrates superior outcome measures
      regarding oxygen saturation, apnea-hypopnea index, and incidence of tracheostomy
      compared with tongue-lip adhesion. CLINICAL QUESTION/LEVEL OF EVIDENCE:
      Therapeutic, III.

PMID- 24569426
TI  - Combined orbital floor wedge implant and fornix reconstruction for
      postenucleation sunken socket syndrome.
AB  - BACKGROUND: The purpose of this study was to evaluate the efficacy of
      simultaneous correction of a postenucleation sunken socket syndrome and deficient
      inferior fornix with a porous polyethylene wedge and oral mucosa graft. METHODS:
      In this study, the authors retrospectively reviewed 24 patients who underwent
      simultaneous correction of postenucleation sunken socket syndrome by wedge
      implants and deficient inferior fornix by oral mucosa graft from January of 2009
      until December of 2011. Upper and lower fornix depths were measured and
      exophthalmometry was performed before and 6 months after surgery. A paired t-test
      analysis was used to compare preoperative and postoperative results of fornix
      depth and exophthalmos. RESULTS: Of the 24 patients, 15 were women and nine were
      men. The mean age of the patients was 44.1 years and the mean follow-up period
      was 11.2 months. Enophthalmos significantly decreased in all cases, with a mean
      change of 3.3 +/- 1.26 mm (p < 0.001). Inferior fornix depth increased
      significantly, with a mean difference of 5.0 +/- 0.86 mm (p < 0.001). There were
      no significant complications after surgery. CONCLUSION: A simultaneous correction
      of postenucleation sunken socket syndrome and deficient inferior fornix using
      porous polyethylene wedge implants and oral mucosa graft can be effective for
      cosmetic improvements in anophthalmic patients. CLINICAL QUESTION/LEVEL OF
      EVIDENCE: Therapeutic, IV.

PMID- 24569427
TI  - Simplifying the management of caudal septal deviation in rhinoplasty.
AB  - SUMMARY: Correction of the deviated nose poses a challenge in even the most
      experienced hands. Frequently, the surgeon is faced with both a functional
      (airway obstruction) and an aesthetic problem that must be addressed conjointly.
      Accurate preoperative analysis and intraoperative diagnosis are integral to good
      outcomes. Caudal septal deviation is frequently present in patients presenting
      for rhinoplasty. The authors' current graduated technique for simplifying the
      management of the caudally deviated septum both aesthetically and functionally is
      described. If there is a persistent caudal septal deviation that has not been
      addressed by standard maneuvers, the caudal portion of the anterior septum is
      resected at the osseocartilaginous junction with the anterior nasal spine and
      maxillary crest and then sutured back to the periosteum of the anterior nasal
      spine with 5-0 polydioxanone. We have found this to be a safe and effective way
      of addressing the caudally deviated septum in the majority of cases.

PMID- 24569428
TI  - Time to re-think the Zurich Guidelines?: a critique on the consensus statement on
      concussion in sport: the 4th International Conference on Concussion in Sport,
      held in Zurich, November 2012.

PMID- 24569430
TI  - Canadian Academy of Sport and Exercise Medicine position statement: athletes at
      high altitude.
AB  - Many sports incorporate training at altitude as a key component of their athlete
      training plan. Furthermore, many sports are required to compete at high altitude
      venues. Exercise at high altitude provides unique challenges to the athlete and
      to the sport medicine clinician working with these athletes. These challenges
      include altitude illness, alterations in training intensity and performance,
      nutritional and hydration difficulties, and challenges related to the austerity
      of the environment. Furthermore, many of the strategies that are typically
      utilized by visitors to altitude may have implications from an anti-doping point
      of view.This position statement was commissioned and approved by the Canadian
      Academy of Sport and Exercise Medicine. The purpose of this statement was to
      provide an evidence-based, best practices summary to assist clinicians with the
      preparation and management of athletes and individuals travelling to altitude for
      both competition and training.

PMID- 24569431
TI  - The contributions of diet and exercise to improving knee osteoarthritis in
      overweight adults.

PMID- 24569429
TI  - 2014 Female Athlete Triad Coalition consensus statement on treatment and return
      to play of the female athlete triad: 1st International Conference held in San
      Francisco, CA, May 2012, and 2nd International Conference held in Indianapolis,
      IN, May 2013.
AB  - The Female Athlete Triad is a medical condition often observed in physically
      active girls and women, and involves 3 components: (1) low energy availability
      with or without disordered eating, (2) menstrual dysfunction, and (3) low bone
      mineral density. Female athletes often present with 1 or more of the 3 Triad
      components, and an early intervention is essential to prevent its progression to
      serious endpoints that include clinical eating disorders, amenorrhea, and
      osteoporosis. This consensus statement represents a set of recommendations
      developed following the first (San Francisco, California) and second
      (Indianapolis, Indianna) International Symposia on the Female Athlete Triad. It
      is intended to provide clinical guidelines for physicians, athletic trainers, and
      other health care providers for the screening, diagnosis, and treatment of the
      Female Athlete Triad and to provide clear recommendations for return to play. The
      2014 Female Athlete Triad Coalition Consensus Statement on Treatment and Return
      to Play of the Female Athlete Triad Expert Panel has proposed a risk
      stratification point system that takes into account magnitude of risk to assist
      the physician in decision-making regarding sport participation, clearance, and
      return to play. Guidelines are offered for clearance categories, management by a
      multidisciplinary team, and implementation of treatment contracts. This consensus
      paper has been endorsed by The Female Athlete Triad Coalition, an International
      Consortium of leading Triad researchers, physicians, and other health care
      professionals, the American College of Sports Medicine, and the American Medical
      Society for Sports Medicine.

PMID- 24569432
TI  - Surgical and nonsurgical treatment of achilles tendon rupture: the favorable
      effect of early functional rehabilitation.

PMID- 24569433
TI  - What are the most important risk factors for hamstring muscle injury?

PMID- 24569434
TI  - Changing level of physical activity and changing degree of happiness.

PMID- 24569436
TI  - Decomposition mechanisms of trinitroalkyl compounds: a theoretical study from
      aliphatic to aromatic nitro compounds.
AB  - The chemical mechanisms involved in the decomposition of trinitroethyl compounds
      were studied for both aliphatic and aromatic derivatives using density functional
      theory calculations. At first, in the case of 1,1,1-trinitrobutane, used as a
      reference molecule, two primary channels were highlighted among the five
      investigated ones: the breaking of the C-N bond and the HONO elimination. Then,
      the influence of various structural parameters was studied for these two
      reactions by changing the length of the carbon chain, adding substituents or
      double bonds along the carbon chain. If some slight changes in activation
      energies were observed for most of these features, no modification of the
      competition between the two investigated reactions was highlighted and the
      breaking of the C-N bond remained the favoured mechanism. At last, the reactions
      involving the trinitroalkyl fragments were highlighted to be more competitive
      than reactions involving nitro groups linked to aromatic cycles in two aromatic
      systems (4-(1,1,1-trinitrobutyl)-nitrobenzene and 2-(1,1,1-trinitrobutyl)
      nitrobenzene). This showed that aromatic nitro compounds with trinitroalkyl
      derivatives decompose from their alkyl part and may be considered more likely as
      aliphatic than as aromatic regarding the initiation of their decomposition
      process. 

PMID- 24569435
TI  - In vivo conversion of astrocytes to neurons in the injured adult spinal cord.
AB  - Spinal cord injury (SCI) leads to irreversible neuronal loss and glial scar
      formation, which ultimately result in persistent neurological dysfunction.
      Cellular regeneration could be an ideal approach to replenish the lost cells and
      repair the damage. However, the adult spinal cord has limited ability to produce
      new neurons. Here we show that resident astrocytes can be converted to
      doublecortin (DCX)-positive neuroblasts by a single transcription factor, SOX2,
      in the injured adult spinal cord. Importantly, these induced neuroblasts can
      mature into synapse-forming neurons in vivo. Neuronal maturation is further
      promoted by treatment with a histone deacetylase inhibitor, valproic acid (VPA).
      The results of this study indicate that in situ reprogramming of endogenous
      astrocytes to neurons might be a potential strategy for cellular regeneration
      after SCI. 

PMID- 24569439
TI  - Analyzing training information from random forests for improved image
      segmentation.
AB  - Labeled training data are used for challenging medical image segmentation
      problems to learn different characteristics of the relevant domain. In this
      paper, we examine random forest (RF) classifiers, their learned knowledge during
      training and ways to exploit it for improved image segmentation. Apart from
      learning discriminative features, RFs also quantify their importance in
      classification. Feature importance is used to design a feature selection strategy
      critical for high segmentation and classification accuracy, and also to design a
      smoothness cost in a second-order MRF framework for graph cut segmentation. The
      cost function combines the contribution of different image features like
      intensity, texture, and curvature information. Experimental results on medical
      images show that this strategy leads to better segmentation accuracy than
      conventional graph cut algorithms that use only intensity information in the
      smoothness cost. 

PMID- 24569438
TI  - Determinants of human papillomavirus coinfections among Montreal university
      students: the influence of behavioral and biologic factors.
AB  - BACKGROUND: Human papillomavirus (HPV) coinfections are common among HPV-infected
      individuals, but the significance and etiology of these infections remain
      unclear. Though current evidence suggests that women with coinfections have
      increased HPV exposure (i.e., more sexual partners), it is also hypothesized that
      these women may represent a subgroup with increased biologic susceptibility. This
      study sought to examine determinants of coinfections in a cohort of young women,
      examining both behavioral and biologic factors related to HPV acquisition over
      time. METHODS: Female university students (n = 537) in Montreal, Canada, were
      followed for 2 years at 6-month intervals. At each visit, cervical specimens were
      collected for cytology and HPV testing, and women completed a questionnaire about
      lifestyle and behavior. HLA alleles were typed from purified DNA collected from
      cervical specimens. Two definitions of coinfections were used: cumulative
      coinfection over follow-up and concurrent coinfection at each visit. Multiple
      logistic regression was used to determine predictors of both cumulative and
      concurrent coinfections using baseline and time-dependent covariates. RESULTS:
      The most consistent determinant of coinfection occurrence was number of sexual
      partners, though several genes of the immune response (HLA-DQB1*06:02, HLA
      G*01:01:03, and HLA-G*01:01:05) were also identified as significant predictors of
      cumulative coinfections. CONCLUSIONS: HPV coinfections mainly occur due to
      increased sexual activity, but biologic susceptibility may also be involved in a
      subset of women. Immunologic factors may put women at greater risk of
      coinfections over the long term, but short-term risk is almost exclusively driven
      by modifiable sexual behaviors. IMPACT: Additional research should continue to
      further identify immunologic biomarkers of HPV susceptibility.

PMID- 24569440
TI  - Image classification using multiscale information fusion based on saliency driven
      nonlinear diffusion filtering.
AB  - In this paper, we propose saliency driven image multiscale nonlinear diffusion
      filtering. The resulting scale space in general preserves or even enhances
      semantically important structures such as edges, lines, or flow-like structures
      in the foreground, and inhibits and smoothes clutter in the background. The image
      is classified using multiscale information fusion based on the original image,
      the image at the final scale at which the diffusion process converges, and the
      image at a midscale. Our algorithm emphasizes the foreground features, which are
      important for image classification. The background image regions, whether
      considered as contexts of the foreground or noise to the foreground, can be
      globally handled by fusing information from different scales. Experimental tests
      of the effectiveness of the multiscale space for the image classification are
      conducted on the following publicly available datasets: 1) the PASCAL 2005
      dataset; 2) the Oxford 102 flowers dataset; and 3) the Oxford 17 flowers dataset,
      with high classification rates.

PMID- 24569437
TI  - Cigarette smoking, physical activity, and alcohol consumption as predictors of
      cancer incidence among women at high risk of breast cancer in the NSABP P-1
      trial.
AB  - BACKGROUND: NSABP P-1 provides an opportunity to examine the association of
      behavioral factors with prospectively monitored cancer incidence and interactions
      with tamoxifen. METHODS: From 1992 to 1997, 13,388 women with estimated 5-year
      breast cancer risk greater than 1.66% or a history of lobular carcinoma in situ
      (87% younger than age 65; 67% postmenopausal) were randomly assigned to tamoxifen
      versus placebo. Invasive breast cancer, lung cancer, colon cancer, and
      endometrial cancer were analyzed with Cox regression. Predictors were baseline
      cigarette smoking, leisure-time physical activity, alcohol consumption, and
      established risk factors. RESULTS: At median 7 years follow-up, we observed 395,
      66, 35, and 74 breast cancer, lung cancer, colon cancer, and endometrial cancer,
      respectively. Women who had smoked were at increased risk of breast cancer (P =
      0.007; HR = 1.3 for 15-35 years smoking, HR = 1.6 for >= 35 years), lung cancer
      (P < 0.001; HR = 3.9 for 15-35 years, HR = 18.4 for >= 35 years), and colon
      cancer (P < 0.001; HR = 5.1 for >= 35 years) versus never-smokers. Low activity
      predicted increased breast cancer risk only among women assigned to placebo (P =
      0.021 activity main effect, P = 0.013 activity-treatment interaction; HR = 1.4
      for the placebo group) and endometrial cancer among all women (P = 0.026, HR =
      1.7). Moderate alcohol (>0-1 drink/day) was associated with decreased risk of
      colon cancer (P = 0.019; HR = 0.35) versus no alcohol. There were no other
      significant associations between these behaviors and cancer risk. CONCLUSION:
      Among women with elevated risk of breast cancer, smoking has an even greater
      impact on breast cancer risk than observed in past studies in the general
      population. IMPACT: Women who smoke or are inactive should be informed of the
      increased risk of multiple types of cancer.

PMID- 24569441
TI  - Quality assessment of stereoscopic 3D image compression by binocular integration
      behaviors.
AB  - The objective approaches of 3D image quality assessment play a key role for the
      development of compression standards and various 3D multimedia applications. The
      quality assessment of 3D images faces more new challenges, such as asymmetric
      stereo compression, depth perception, and virtual view synthesis, than its 2D
      counterparts. In addition, the widely used 2D image quality metrics (e.g., PSNR
      and SSIM) cannot be directly applied to deal with these newly introduced
      challenges. This statement can be verified by the low correlation between the
      computed objective measures and the subjectively measured mean opinion scores
      (MOSs), when 3D images are the tested targets. In order to meet these newly
      introduced challenges, in this paper, besides traditional 2D image metrics, the
      binocular integration behaviors-the binocular combination and the binocular
      frequency integration, are utilized as the bases for measuring the quality of
      stereoscopic 3D images. The effectiveness of the proposed metrics is verified by
      conducting subjective evaluations on publicly available stereoscopic image
      databases. Experimental results show that significant consistency could be
      reached between the measured MOS and the proposed metrics, in which the
      correlation coefficient between them can go up to 0.88. Furthermore, we found
      that the proposed metrics can also address the quality assessment of the
      synthesized color-plus-depth 3D images well. Therefore, it is our belief that the
      binocular integration behaviors are important factors in the development of
      objective quality assessment for 3D images. 

PMID- 24569442
TI  - Parsimonious path openings and closings.
AB  - Path openings and closings are morphological tools used to preserve long, thin,
      and tortuous structures in gray level images. They explore all paths from a
      defined class, and filter them with a length criterion. However, most paths are
      redundant, making the process generally slow. Parsimonious path openings and
      closings are introduced in this paper to solve this problem. These operators only
      consider a subset of the paths considered by classical path openings, thus
      achieving a substantial speed-up, while obtaining similar results. In addition, a
      recently introduced 1D opening algorithm is applied along each selected path. Its
      complexity is linear with respect to the number of pixels, independent of the
      size of the opening. Furthermore, it is fast for any input data accuracy (integer
      or floating point) and works in stream. Parsimonious path openings are also
      extended to incomplete paths, i.e., paths containing gaps. Noise-corrupted paths
      can thus be processed with the same approach and complexity. These parsimonious
      operators achieve a several orders of magnitude speed-up. Examples are shown for
      incomplete path openings, where computing times are brought from minutes to tens
      of milliseconds, while obtaining similar results. 

PMID- 24569443
TI  - Data-driven spatially-adaptive metric adjustment for visual tracking.
AB  - Matching visual appearances of the target over consecutive video frames is a
      fundamental yet challenging task in visual tracking. Its performance largely
      depends on the distance metric that determines the quality of visual matching.
      Rather than using fixed and predefined metric, recent attempts of integrating
      metric learning-based trackers have shown more robust and promising results, as
      the learned metric can be more discriminative. In general, these global metric
      adjustment methods are computationally demanding in real-time visual tracking
      tasks, and they tend to underfit the data when the target exhibits dynamic
      appearance variation. This paper presents a nonparametric data-driven local
      metric adjustment method. The proposed method finds a spatially adaptive metric
      that exhibits different properties at different locations in the feature space,
      due to the differences of the data distribution in a local neighborhood. It
      minimizes the deviation of the empirical misclassification probability to obtain
      the optimal metric such that the asymptotic error as if using an infinite set of
      training samples can be approximated. Moreover, by taking the data local
      distribution into consideration, it is spatially adaptive. Integrating this new
      local metric learning method into target tracking leads to efficient and robust
      tracking performance. Extensive experiments have demonstrated the superiority and
      effectiveness of the proposed tracking method in various tracking scenarios. 

PMID- 24569445
TI  - Melanoma: blocking BRAF to the BRIM.

PMID- 24569444
TI  - Ultra-flexibility and unusual electronic, magnetic and chemical properties of
      waved graphenes and nanoribbons.
AB  - Two-dimensional materials have attracted increasing attention because of their
      particular properties and potential applications in next-generation nanodevices.
      In this work, we investigate the physical and chemical properties of waved
      graphenes/nanoribbons based on first-principles calculations. We show that waved
      graphenes are compressible up to a strain of 50% and ultra-flexible because of
      the vanishing in-plane stiffness. The conductivity of waved graphenes is reduced
      due to charge decoupling under high compression. Our analysis of pyramidalization
      angles predicts that the chemistry of waved graphenes can be easily controlled by
      modulating local curvatures. We further demonstrate that band gaps of armchair
      waved graphene nanoribbons decrease with the increase of compression if they are
      asymmetrical in geometry, while increase if symmetrical. For waved zigzag
      nanoribbons, their anti-ferromagnetic states are strongly enhanced by increasing
      compression. The versatile functions of waved graphenes enable their applications
      in multi-functional nanodevices and sensors. 

PMID- 24569446
TI  - Genetics: what do breast and bladder cancer have in common?

PMID- 24569447
TI  - Cancer therapy: could vitamin C be a useful adjunct to chemotherapy?

PMID- 24569449
TI  - Prevention: daily aspirin and chemoprevention.

PMID- 24569450
TI  - Favourable 5-year postdischarge survival of comatose patients resuscitated from
      out-of-hospital cardiac arrest, managed with immediate coronary angiogram on
      admission.
AB  - AIMS: On-admission coronary angiogram (CA) with angioplasty (percutaneous
      coronary intervention, PCI) may improve survival in patients resuscitated from
      out-of-hospital cardiac arrest (OHCA), but long-term survival data are scarce. We
      assessed long-term survival in OHCA patients managed with on-admission CA and PCI
      if indicated and compared survival rates in patients with/without acute coronary
      syndrome (ACS). METHODS: Retrospective single-centre study including patients
      aged >=18 years resuscitated from an OHCA without noncardiac cause, with
      sustained return of spontaneous circulation, undergoing on-admission CA with PCI
      if indicated. ACS was diagnosed angiographically. Survival was recorded at
      hospital discharge and at 5-year follow up. Survival probability was estimated by
      Kaplan-Meier survival curves. RESULTS: A total of 300 comatose patients aged 56
      years (IQR 48-67 years) were included, 36% with ST-segment elevation. All had on
      admission CA; 31% had ACS. PCI was attempted in 91% of ACS patients and was
      successful in 93%. Hypothermia was performed in 84%. Survival to discharge was
      32.3%. After discharge, 5-year survival was 81.7 +/- 5.4%. Survival from
      admission to 5 years was 26.2 +/- 2.8%. ACS patients had better survival to
      discharge (40.8%) compared with non-ACS patients (28.5%, p=0.047). After
      discharge, 5-year survival was 92.2 +/- 5.4% for patients with ACS and 73.4 +/-
      8.6% without ACS (hazard ratio, HR, 2.7, 95% CI 0.8-8.9, p=0.1). Survival from
      admission to 5 years was 37.4 +/- 5.2% for ACS patients, 20.7 +/- 3.0%, for non
      ACS patients (HR 1.5, 95% CI 1.12-2.0, p=0.0067). CONCLUSIONS: OHCA patients
      undergoing on-admission CA had a very favourable postdischarge survival. Patients
      with OHCA due to ACS had better survival to discharge at 5-year follow up than
      patients with OHCA due to other causes.

PMID- 24569451
TI  - Are respiratory complications more likely in patients with pulmonary
      aspergillosis treated with echinocandins in the setting of neutrophil influx?

PMID- 24569452
TI  - Soluble TNFRp75 regulates host protective immunity against Mycobacterium
      tuberculosis.
AB  - Development of host protective immunity against Mycobacterium tuberculosis
      infection is critically dependent on the inflammatory cytokine TNF. TNF signals
      through 2 receptors, TNFRp55 and TNFRp75; however, the role of TNFRp75-dependent
      signaling in immune regulation is poorly defined. Here we found that mice lacking
      TNFRp75 exhibit greater control of M. tuberculosis infection compared with WT
      mice. TNFRp75-/- mice developed effective bactericidal granulomas and
      demonstrated increased pulmonary recruitment of activated DCs. Moreover, IL-12p40
      dependent migration of DCs to lung draining LNs of infected TNFRp75-/- mice was
      substantially higher than that observed in WT M. tuberculosis-infected animals
      and was associated with enhanced frequencies of activated M. tuberculosis
      specific IFN-gamma-expressing CD4+ T cells. In WT mice, TNFRp75 shedding
      correlated with markedly reduced bioactive TNF levels and IL-12p40 expression.
      Neutralization of TNFRp75 in M. tuberculosis-infected WT BM-derived DCs (BMDCs)
      increased production of bioactive TNF and IL-12p40 to a level equivalent to that
      produced by TNFRp75-/- BMDCs. Addition of exogenous TNFRp75 to TNFRp75-/- BMDCs
      infected with M. tuberculosis decreased IL-12p40 synthesis, demonstrating that
      TNFRp75 shedding regulates DC activation. These data indicate that TNFRp75
      shedding downmodulates protective immune function and reduces host resistance and
      survival; therefore, targeting TNFRp75 may be beneficial for improving disease
      outcome. 

PMID- 24569448
TI  - Current approaches to the treatment of metastatic brain tumours.
AB  - Metastatic tumours involving the brain overshadow primary brain neoplasms in
      frequency and are an important complication in the overall management of many
      cancers. Importantly, advances are being made in understanding the molecular
      biology underlying the initial development and eventual proliferation of brain
      metastases. Surgery and radiation remain the cornerstones of the therapy for
      symptomatic lesions; however, image-based guidance is improving surgical
      technique to maximize the preservation of normal tissue, while more sophisticated
      approaches to radiation therapy are being used to minimize the long-standing
      concerns over the toxicity of whole-brain radiation protocols used in the past.
      Furthermore, the burgeoning knowledge of tumour biology has facilitated the entry
      of systemically administered therapies into the clinic. Responses to these
      targeted interventions have ranged from substantial toxicity with no control of
      disease to periods of useful tumour control with no decrement in performance
      status of the treated individual. This experience enables recognition of the
      limits of targeted therapy, but has also informed methods to optimize this
      approach. This Review focuses on the clinically relevant molecular biology of
      brain metastases, and summarizes the current applications of these data to
      imaging, surgery, radiation therapy, cytotoxic chemotherapy and targeted therapy.

PMID- 24569453
TI  - Interactions between Siglec-7/9 receptors and ligands influence NK cell-dependent
      tumor immunosurveillance.
AB  - Alteration of the surface glycosylation pattern on malignant cells potentially
      affects tumor immunity by directly influencing interactions with glycan-binding
      proteins (lectins) on the surface of immunomodulatory cells. The sialic acid
      binding Ig-like lectins Siglec-7 and -9 are MHC class I-independent inhibitory
      receptors on human NK cells that recognize sialic acid-containing carbohydrates.
      Here, we found that the presence of Siglec-9 defined a subset of cytotoxic NK
      cells with a mature phenotype and enhanced chemotactic potential. Interestingly,
      this Siglec-9+ NK cell population was reduced in the peripheral blood of cancer
      patients. Broad analysis of primary tumor samples revealed that ligands of Siglec
      7 and -9 were expressed on human cancer cells of different histological types.
      Expression of Siglec-7 and -9 ligands was associated with susceptibility of NK
      cell-sensitive tumor cells and, unexpectedly, of presumably NK cell-resistant
      tumor cells to NK cell-mediated cytotoxicity. Together, these observations have
      direct implications for NK cell-based therapies and highlight the requirement to
      consider both MHC class I haplotype and tumor-specific glycosylation. 

PMID- 24569454
TI  - IL-7 receptor blockade following T cell depletion promotes long-term allograft
      survival.
AB  - T cell depletion is commonly used in organ transplantation for immunosuppression;
      however, a restoration of T cell homeostasis following depletion leads to
      increased memory T cells, which may promote transplant rejection. The cytokine IL
      7 is important for controlling lymphopoiesis under both normal and lymphopenic
      conditions. Here, we investigated whether blocking IL-7 signaling with a mAb that
      targets IL-7 receptor alpha (IL-7Ralpha) alone or following T cell depletion
      confers an advantage for allograft survival in murine transplant models. We found
      that IL-7R blockade alone induced indefinite pancreatic islet allograft survival
      if anti-IL-7R treatment was started 3 weeks before graft. IL-7R blockade
      following anti-CD4- and anti-CD8-mediated T cell depletion markedly prolonged
      skin allograft survival. Furthermore, IL-7 inhibition in combination with T cell
      depletion synergized with either CTLA-4Ig administration or suboptimal doses of
      tacrolimus to induce long-term skin graft acceptance in this stringent transplant
      model. Together, these therapies inhibited T cell reconstitution, decreased
      memory T cell numbers, increased the relative frequency of Tregs, and abrogated
      both cellular and humoral alloimmune responses. Our data suggest that IL-7R
      blockade following T cell depletion has potential as a robust, immunosuppressive
      therapy in transplantation. 

PMID- 24569455
TI  - Familial Alzheimer's disease-associated presenilin-1 alters cerebellar activity
      and calcium homeostasis.
AB  - Familial Alzheimer's disease (FAD) is characterized by autosomal dominant
      heritability and early disease onset. Mutations in the gene encoding presenilin-1
      (PS1) are found in approximately 80% of cases of FAD, with some of these patients
      presenting cerebellar damage with amyloid plaques and ataxia with unclear
      pathophysiology. A Colombian kindred carrying the PS1-E280A mutation is the
      largest known cohort of PS1-FAD patients. Here, we investigated PS1-E280A
      associated cerebellar dysfunction and found that it occurs early in PS1-E208A
      carriers, while cerebellar signs are highly prevalent in patients with dementia.
      Postmortem analysis of cerebella of PS1-E280A carrier revealed greater Purkinje
      cell (PC) loss and more abnormal mitochondria compared with controls. In PS1
      E280A tissue, ER/mitochondria tethering was impaired, Ca2+ channels IP3Rs and
      CACNA1A were downregulated, and Ca2+-dependent mitochondrial transport proteins
      MIRO1 and KIF5C were reduced. Accordingly, expression of PS1-E280A in a neuronal
      cell line altered ER/mitochondria tethering and transport compared with that in
      cells expressing wild-type PS1. In a murine model of PS1-FAD, animals exhibited
      mild ataxia and reduced PC simple spike activity prior to cerebellar beta-amyloid
      deposition. Our data suggest that impaired calcium homeostasis and mitochondrial
      dysfunction in PS1-FAD PCs reduces their activity and contributes to motor
      coordination deficits prior to Abeta aggregation and dementia. We propose that
      PS1-E280A affects both Ca2+ homeostasis and Abeta precursor processing, leading
      to FAD and neurodegeneration. 

PMID- 24569456
TI  - Hematopoiesis and RAS-driven myeloid leukemia differentially require PI3K isoform
      p110alpha.
AB  - The genes encoding RAS family members are frequently mutated in juvenile
      myelomonocytic leukemia (JMML) and acute myeloid leukemia (AML). RAS proteins are
      difficult to target pharmacologically; therefore, targeting the downstream PI3K
      and RAF/MEK/ERK pathways represents a promising approach to treat RAS-addicted
      tumors. The p110alpha isoform of PI3K (encoded by Pik3ca) is an essential
      effector of oncogenic KRAS in murine lung tumors, but it is unknown whether
      p110alpha contributes to leukemia. To specifically examine the role of p110alpha
      in murine hematopoiesis and in leukemia, we conditionally deleted p110alpha in
      HSCs using the Cre-loxP system. Postnatal deletion of p110alpha resulted in mild
      anemia without affecting HSC self-renewal; however, deletion of p110alpha in mice
      with KRASG12D-associated JMML markedly delayed their death. Furthermore, the
      p110alpha-selective inhibitor BYL719 inhibited growth factor-independent KRASG12D
      BM colony formation and sensitized cells to a low dose of the MEK inhibitor
      MEK162. Furthermore, combined inhibition of p110alpha and MEK effectively reduced
      proliferation of RAS-mutated AML cell lines and disease in an AML murine
      xenograft model. Together, our data indicate that RAS-mutated myeloid leukemias
      are dependent on the PI3K isoform p110alpha, and combined pharmacologic
      inhibition of p110alpha and MEK could be an effective therapeutic strategy for
      JMML and AML. 

PMID- 24569457
TI  - Pegylated IFN-alpha regulates hepatic gene expression through transient Jak/STAT
      activation.
AB  - The use of pegylated interferon-alpha (pegIFN-alpha) has replaced unmodified
      recombinant IFN-alpha for the treatment of chronic viral hepatitis. While the
      superior antiviral efficacy of pegIFN-alpha is generally attributed to improved
      pharmacokinetic properties, the pharmacodynamic effects of pegIFN-alpha in the
      liver have not been studied. Here, we analyzed pegIFN-alpha-induced signaling and
      gene regulation in paired liver biopsies obtained prior to treatment and during
      the first week following pegIFN-alpha injection in 18 patients with chronic
      hepatitis C. Despite sustained high concentrations of pegIFN-alpha in serum, the
      Jak/STAT pathway was activated in hepatocytes only on the first day after pegIFN
      alpha administration. Evaluation of liver biopsies revealed that pegIFN-alpha
      induces hundreds of genes that can be classified into four clusters based on
      different temporal expression profiles. In all clusters, gene transcription was
      mainly driven by IFN-stimulated gene factor 3 (ISGF3). Compared with conventional
      IFN-alpha therapy, pegIFN-alpha induced a broader spectrum of gene expression,
      including many genes involved in cellular immunity. IFN-induced secondary
      transcription factors did not result in additional waves of gene expression. Our
      data indicate that the superior antiviral efficacy of pegIFN-alpha is not the
      result of prolonged Jak/STAT pathway activation in hepatocytes, but rather is due
      to induction of additional genes that are involved in cellular immune responses. 

PMID- 24569458
TI  - Oncogenic and sorafenib-sensitive ARAF mutations in lung adenocarcinoma.
AB  - Targeted cancer therapies often induce "outlier" responses in molecularly defined
      patient subsets. One patient with advanced-stage lung adenocarcinoma, who was
      treated with oral sorafenib, demonstrated a near-complete clinical and
      radiographic remission for 5 years. Whole-genome sequencing and RNA sequencing of
      primary tumor and normal samples from this patient identified a somatic mutation,
      ARAF S214C, present in the cancer genome and expressed at high levels. Additional
      mutations affecting this residue of ARAF and a nearby residue in the related
      kinase RAF1 were demonstrated across 1% of an independent cohort of lung
      adenocarcinoma cases. The ARAF mutations were shown to transform immortalized
      human airway epithelial cells in a sorafenib-sensitive manner. These results
      suggest that mutant ARAF is an oncogenic driver in lung adenocarcinoma and an
      indicator of sorafenib response. 

PMID- 24569459
TI  - Randomized trial of the anti-FGF23 antibody KRN23 in X-linked hypophosphatemia.
AB  - BACKGROUND: X-linked hypophosphatemia (XLH) is the most common heritable form of
      rickets and osteomalacia. XLH-associated mutations in phosphate-regulating
      endopeptidase (PHEX) result in elevated serum FGF23, decreased renal phosphate
      reabsorption, and low serum concentrations of phosphate (inorganic phosphorus,
      Pi) and 1,25-dihydroxyvitamin D [1,25(OH)2D]. KRN23 is a human anti-FGF23
      antibody developed as a potential treatment for XLH. Here, we have assessed the
      safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and
      immunogenicity of KRN23 following a single i.v. or s.c. dose of KRN23 in adults
      with XLH. METHODS: Thirty-eight XLH patients were randomized to receive a single
      dose of KRN23 (0.003-0.3 mg/kg i.v. or 0.1-1 mg/kg s.c.) or placebo. PK, PD,
      immunogenicity, safety, and tolerability were assessed for up to 50 days.
      RESULTS: KRN23 significantly increased the maximum renal tubular threshold for
      phosphate reabsorption (TmP/GFR), serum Pi, and 1,25(OH)2D compared with that of
      placebo (P<0.01). The maximum serum Pi concentration occurred later following
      s.c. dosing (8-15 days) compared with that seen with i.v. dosing (0.5-4 days).
      The effect duration was dose related and persisted longer in patients who
      received s.c. administration. Changes from baseline in TmP/GFR, serum Pi, and
      serum 1,25(OH)2D correlated with serum KRN23 concentrations. The mean t1/2 of
      KRN23 was 8-12 days after i.v. administration and 13-19 days after s.c.
      administration. Patients did not exhibit increased nephrocalcinosis or develop
      hypercalciuria, hypercalcemia, anti-KRN23 antibodies, or elevated serum
      parathyroid hormone (PTH) or creatinine. CONCLUSION: KRN23 increased TmP/GFR,
      serum Pi, and serum 1,25(OH)2D. The positive effect of KR23 on serum Pi and its
      favorable safety profile suggest utility for KRN23 in XLH patients. Trial
      registration. Clinicaltrials.gov NCT00830674. Funding. Kyowa Hakko Kirin Pharma,
      Inc.

PMID- 24569460
TI  - Selective AKR1C3 inhibitors do not recapitulate the anti-leukaemic activities of
      the pan-AKR1C inhibitor medroxyprogesterone acetate.
AB  - BACKGROUND: We and others have identified the aldo-keto reductase AKR1C3 as a
      potential drug target in prostate cancer, breast cancer and leukaemia. As a
      consequence, significant effort is being invested in the development of AKR1C3
      selective inhibitors. METHODS: We report the screening of an in-house drug
      library to identify known drugs that selectively inhibit AKR1C3 over the closely
      related isoforms AKR1C1, 1C2 and 1C4. This screen initially identified
      tetracycline as a potential AKR1C3-selective inhibitor. However, mass
      spectrometry and nuclear magnetic resonance studies identified that the active
      agent was a novel breakdown product (4-methyl(de-dimethylamine)-tetracycline (4
      MDDT)). RESULTS: We demonstrate that, although 4-MDDT enters AML cells and
      inhibits their AKR1C3 activity, it does not recapitulate the anti-leukaemic
      actions of the pan-AKR1C inhibitor medroxyprogesterone acetate (MPA). Screens of
      the NCI diversity set and an independently curated small-molecule library
      identified several additional AKR1C3-selective inhibitors, none of which had the
      expected anti-leukaemic activity. However, a pan AKR1C, also identified in the
      NCI diversity set faithfully recapitulated the actions of MPA. CONCLUSIONS: In
      summary, we have identified a novel tetracycline-derived product that provides an
      excellent lead structure with proven drug-like qualities for the development of
      AKR1C3 inhibitors. However, our findings suggest that, at least in leukaemia,
      selective inhibition of AKR1C3 is insufficient to elicit an anticancer effect and
      that multiple AKR1C inhibition may be required.

PMID- 24569462
TI  - Distinguishing sedentary from inactive: implications for meta-analyses.

PMID- 24569461
TI  - Alpha-1-fucosidase as a prognostic indicator for hepatocellular carcinoma
      following hepatectomy: a large-scale, long-term study.
AB  - BACKGROUND: Preoperative alpha-L-fucosidase (AFU) has been used as a diagnostic
      biomarker for hepatocellular carcinoma (HCC), but its role as a prognostic
      predictor after partial hepatectomy has not been well defined. The study aimed to
      investigate the prognostic significance of preoperative serum AFU for HCC
      patients after hepatic resection. METHODS: A retrospective training data set and
      a prospective validation data set were used to evaluate the prognosis of HCC
      after partial hepatectomy. A total of 669 patients with histopathologically
      confirmed HCC were enrolled. Univariate and multivariate analyses were used to
      identify the prognostic significance of preoperative serum AFU. RESULTS: The
      retrospective training data set showed a preoperative AFU>35 u l(-1) should be
      used. The prospective validation data set showed preoperative AFU was an
      independent prognostic factor of overall survival (OS) (P=0.008; hazard ratio:
      2.333; 95% confidence interval: 1.249-4.369). Patients with a preoperative AFU>35
      u l(-1) had a lower recurrence-free survival rate and an OS rate than those with
      AFU<=35 u l(-1), and they have a higher tendency to form macrovascular invasion.
      Furthermore, the prognostic significance of AFU>35 u l(-1) could also be applied
      to patients with alpha-fetoprotein levels of <=400 ng ml(-1). CONCLUSIONS:
      Preoperative serum AFU is a prognostic predictor of HCC.

PMID- 24569463
TI  - Eribulin mesilate suppresses experimental metastasis of breast cancer cells by
      reversing phenotype from epithelial-mesenchymal transition (EMT) to mesenchymal
      epithelial transition (MET) states.
AB  - BACKGROUND: Eribulin mesilate (eribulin), a non-taxane microtubule dynamics
      inhibitor, has shown trends towards greater overall survival (OS) compared with
      progression-free survival in late-stage metastatic breast cancer patients in the
      clinic. This finding suggests that eribulin may have additional, previously
      unrecognised antitumour mechanisms beyond its established antimitotic activity.
      To investigate this possibility, eribulin's effects on the balance between
      epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition
      (MET) in human breast cancer cells were investigated. METHODS: Triple negative
      breast cancer (TNBC) cells, which are oestrogen receptor (ER-)/progesterone
      receptor (PR-)/human epithelial growth receptor 2 (HER2-) and have a mesenchymal
      phenotype, were treated with eribulin for 7 days, followed by measurement of EMT
      related gene and protein expression changes in the surviving cells by
      quantitative real-time PCR (qPCR) and immunoblot, respectively. In addition,
      proliferation, migration, and invasion assays were also conducted in eribulin
      treated cells. To investigate the effects of eribulin on TGF-beta/Smad
      signalling, the phosphorylation status of Smad proteins was analysed. In vivo,
      the EMT/MET status of TNBC xenografts in mice treated with eribulin was examined
      by qPCR, immunoblot, and immunohistochemical analysis. Finally, an experimental
      lung metastasis model was utilised to gauge the metastatic activity of eribulin
      treated TNBC in the in vivo setting. RESULTS: Treatment of TNBC cells with
      eribulin in vitro led to morphological changes consistent with transition from a
      mesenchymal to an epithelial phenotype. Expression analyses of EMT markers showed
      that eribulin treatment led to decreased expression of several mesenchymal marker
      genes, together with increased expression of several epithelial markers. In the
      TGF-beta induced EMT model, eribulin treatment reversed EMT, coincident with
      inhibition of Smad2 and Smad3 phosphorylation. Consistent with these changes,
      TNBC cells treated with eribulin for 7 days showed decreased capacity for in
      vitro migration and invasiveness. In in vivo xenograft models, eribulin treatment
      reversed EMT and induced MET as assessed by qPCR, immunoblot, and
      immunohistochemical analyses of epithelial and mesenchymal marker proteins.
      Finally, surviving TNBC cells pretreated in vitro with eribulin for 7 days led to
      decreased numbers of lung metastasis when assessed in an in vivo experimental
      metastasis model. CONCLUSIONS: Eribulin exerted significant effects on EMT/MET
      related pathway components in human breast cancer cells in vitro and in vivo,
      consistent with a phenotypic switch from mesenchymal to epithelial states, and
      corresponding to observed decreases in migration and invasiveness in vitro as
      well as experimental metastasis in vivo. These preclinical findings may provide a
      plausible scientific basis for clinical observations of prolonged OS by
      suppression of further spread of metastasis in breast cancer patients treated
      with eribulin.

PMID- 24569465
TI  - Reply: Comment on 'Association of sedentary behaviour with colon and rectal
      cancer: a meta-analysis of observational studies'.

PMID- 24569464
TI  - Phase I/II study of verteporfin photodynamic therapy in locally advanced
      pancreatic cancer.
AB  - BACKGROUND: Patients with pancreatic cancer have a poor prognosis apart from the
      few suitable for surgery. Photodynamic therapy (PDT) produces localised tissue
      necrosis but previous studies using the photosensitiser meso
      tetrahydroxyphenylchlorin (mTHPC) caused prolonged skin photosensitivity. This
      study assessed a shorter acting photosensitiser, verteporfin. METHODS: Fifteen
      inoperable patients with locally advanced cancers were sensitised with 0.4 mg kg(
      1) verteporfin. After 60-90 min, laser light (690 nm) was delivered via single
      (13 patients) or multiple (2 patients) fibres positioned percutaneously under
      computed tomography (CT) guidance, the light dose escalating (initially 5 J,
      doubling after each three patients) until 12 mm of necrosis was achieved
      consistently. RESULTS: In all, 12 mm lesions were seen consistently at 40 J, but
      with considerable variation in necrosis volume (mean volume 3.5 cm(3) at 40 J).
      Minor, self-limiting extrapancreatic effects were seen in multifibre patients. No
      adverse interactions were seen in patients given chemotherapy or radiotherapy
      before or after PDT. After PDT, one patient underwent an R0 Whipple's
      pancreaticoduodenectomy. CONCLUSIONS: Verteporfin PDT-induced tumour necrosis in
      locally advanced pancreatic cancer is feasible and safe. It can be delivered with
      a much shorter drug light interval and with less photosensitivity than with older
      compounds.

PMID- 24569466
TI  - Diabetes and prognosis in older persons with colorectal cancer.
AB  - BACKGROUND: Epidemiological studies have reported that diabetes significantly
      increases overall mortality in patients with colorectal cancer. However, it is
      unclear whether diabetes increases colorectal cancer-specific mortality. We used
      the US Surveillance Epidemiology and End Results (SEER) database linked with
      Medicare claims data to assess the influence of pre-existing diabetes on
      prognosis of patients with colorectal cancer. METHODS: Data from 61,213 patients
      aged 67 or older with colorectal cancer diagnosed between 2003 and 2009 were
      extracted and prospectively followed through the date of death or the end of 2012
      if the patient was still alive. Diabetes cases with and without complications
      were identified based on an algorithm developed for the Chronic Condition Data
      Warehouse (CCW). Cox models were used to estimate hazard ratios (HRs) for total
      mortality. The proportional subdistribution hazards model proposed by Fine and
      Gray was used to estimate HRs for colorectal cancer-specific mortality. RESULTS:
      Compared with patients without diabetes, colorectal cancer patients with pre
      existing diabetes had significantly higher risk of overall mortality (HR=1.20, 95
      % confidence interval (95% CI): 1.17-1.23). The HR for overall mortality was more
      pronounced for patients who had diabetes with complications (HR=1.50, 95% CI:
      1.42-1.58). However, diabetes was not associated with increased colorectal cancer
      specific mortality after accounting for non-colorectal cancer outcomes as
      competing risk. CONCLUSIONS: Pre-existing diabetes increased risk of total
      mortality among patients with colorectal cancer, especially among cancer patients
      who had diabetes with complications. The increased risk of total mortality
      associated with diabetes was primarily explained by increased cardiovascular
      specific mortality, not by increased colorectal cancer-specific mortality.

PMID- 24569467
TI  - Long-term survival of advanced triple-negative breast cancers with a dose-intense
      cyclophosphamide/anthracycline neoadjuvant regimen.
AB  - BACKGROUND: Triple-negative (TN) breast cancers exhibit major initial responses
      to neoadjuvant chemotherapy, but generally have a poor outcome. Because of the
      lack of validated drug targets, chemotherapy remains an important therapeutic
      tool in these cancers. METHODS: We report the survival of two consecutive series
      of 267 locally advanced breast cancers (LABC) treated with two different
      neoadjuvant regimens, either a dose-dense and dose-intense cyclophosphamide
      anthracycline (AC) association (historically called SIM) or a conventional
      sequential association of cyclophosphamide and anthracycline, followed by taxanes
      (EC-T). We compared pathological responses and survival rates of these two groups
      and studied their association with tumours features. RESULTS: Although the two
      regimens showed equivalent pathological complete response (pCR) in the whole
      population (16 and 12%), the SIM regimen yielded a non-statistically higher pCR
      rate than EC-T (48% vs 24%, P=0.087) in TN tumours. In the SIM protocol, DFS was
      statistically higher for TN than for non-TN patients (P=0.019), although we
      showed that the TN status was associated with an increased initial risk of
      recurrence in both regimens. This effect gradually decreased and after 2 years,
      TN was associated with a significantly decreased likelihood of relapse in SIM
      treated LABC (hazard ratio (HR)=0.25 (95% CI: 0.07-0.86), P=0.028). CONCLUSIONS:
      AC dose intensification treatment is associated with a very favourable long-term
      survival rate in TN breast cancers. These observations call for a prospective
      assessment of such dose-intense AC-based regimens in locally advanced TN tumours.

PMID- 24569468
TI  - A novel staging model to classify oesophageal squamous cell carcinoma patients in
      China.
AB  - BACKGROUND: Oesophageal squamous cell carcinoma (ESCC) is the predominant subtype
      of oesophageal carcinoma in China, with the overall 5-year survival rate of <10%.
      The current tumour-node-metastasis (TNM) staging system has become so complex
      that it is not easy to use in the life expectancy assessment. We aim to combine
      clinical variables and biomarkers to develop and validate a relative simple and
      reliable model, named the FENSAM, for ESCC prognosis. METHODS: To build the
      FENSAM, we analysed 22 potential prognostic factors from 461 patients, including
      9 biomarkers (Ezrin, Fascin, desmocollin 2 (DSC2), pFascin, activating
      transcription factor 3 (ATF3), connective-tissue growth factor (CTGF), neutrophil
      gelatinase-associated lipocalin (NGAL), NGAL receptor (NGALR), and cysteine-rich
      angiogenic protein 61 (CYR61)) and other 13 clinical variables. We selected
      significant factors associated with survival of ESCC patients, and used them to
      build our FENSAM model. We then obtained the hazard risk score of the model to
      classify ESCC patients. In addition, we validated the model in an independent
      cohort of 290 patients from the same hospital. The predictive performance of the
      model was assessed by the Area under the Receiver Operating Characteristic Curve
      (AUC) and Kaplan-Meier survival analysis. RESULTS: We found six markers
      significantly associated with survival of ESCC patients (Ezrin, Fascin, ATF3,
      surgery extent, N-stage, and M-stage). They were combined to create a novel four
      stage FENSAM model for patients' classification. FENSAM possessed a high
      classification precision similar to the TNM staging system, but with a much
      simpler model. The efficiency of FENSAM was evaluated by different quantiles of
      AUC and the results of survival analysis. The validation result demonstrated the
      potential of the FENSAM model to improve classification accuracy for ESCC
      patients. CONCLUSIONS: FENSAM provides an alternative classifier for ESCC
      patients with a high classification precision using a simple model.

PMID- 24569469
TI  - Does the cancer drugs fund lead to faster uptake of cost-effective drugs? A time
      trend analysis comparing England and Wales.
AB  - BACKGROUND: The Cancer Drugs Fund (CDF) provides L200 million annually in England
      for 'anti-cancer' drugs. METHODS: We used a controlled pre-/post-intervention
      design to compare IMS Health dispensing data for 15 cancer drugs (2007-2012) in
      England vs Wales, stratified by pre-CDF NICE drug approval status (rejected,
      mixed recommendations, recommended, not appraised). RESULTS: The CDF was
      associated with increased prescribing in England for three of five drugs rejected
      or with mixed NICE recommendations. The prescribing volume ratios (PVR) ranged
      from 1.29 (95% CI 1.00, 1.67) for sorafenib to 3.28 (2.59, 4.14) for bevacizumab
      (NICE rejected) and 0.93 (0.81, 1.06) and 1.35 (1.21, 1.49) for sunitinib and
      imatinib respectively (mixed recommendations). Post CDF prescribing in England
      increased for both drugs awaiting NICE appraisal pre-CDF (lapatinib PVR=7.44
      (5.81, 9.54), panitumumab PVR=5.40 (1.20, 24.42)) and subsequently rejected. The
      CDF was not associated with increased prescribing in England of NICE-recommended
      drugs. The three most recently launched, subsequently recommended drugs were
      adopted faster in Wales (from pazopanib PVR=0.51 (0.28, 0.96) to abiraterone
      PVR=0.78 (0.61-0.99)). INTERPRETATION: These data indicate that the CDF is used
      to access drugs deemed not cost-effective by NICE. The CDF did not expedite
      access to new cost-effective cancer agents prior to NICE approval.

PMID- 24569470
TI  - Paediatric head CT scan and subsequent risk of malignancy and benign brain
      tumour: a nation-wide population-based cohort study.
AB  - BACKGROUND: To evaluate the possible association between paediatric head computed
      tomography (CT) examination and increased subsequent risk of malignancy and
      benign brain tumour. METHODS: In the exposed cohort, 24 418 participants under 18
      years of age, who underwent head CT examination between 1998 and 2006, were
      identified from the Taiwan National Health Insurance Research Database (NHIRD).
      Patients were followed up until a diagnosis of malignant disease or benign brain
      tumour, withdrawal from the National Health Insurance (NHI) system, or at the end
      of 2008. RESULTS: The overall risk was not significantly different in the two
      cohorts (incidence rate=36.72 per 100 000 person-years in the exposed cohort,
      28.48 per 100 000 person-years in the unexposed cohort, hazard ratio (HR)=1.29,
      95% confidence interval (CI)=0.90-1.85). The risk of benign brain tumour was
      significantly higher in the exposed cohort than in the unexposed cohort (HR=2.97,
      95% CI=1.49-5.93). The frequency of CT examination showed strong correlation with
      the subsequent overall risk of malignancy and benign brain tumour. CONCLUSIONS:
      We found that paediatric head CT examination was associated with an increased
      incidence of benign brain tumour. A large-scale study with longer follow-up is
      necessary to confirm this result.

PMID- 24569471
TI  - Tumour biomechanical response to the vascular disrupting agent ZD6126 in vivo
      assessed by magnetic resonance elastography.
AB  - BACKGROUND: Magnetic resonance elastography (MRE) is an emerging imaging
      technique that affords non-invasive quantitative assessment and visualization of
      tissue mechanical properties in vivo. METHODS: In this study, MRE was used to
      quantify (kPa) the absolute value of the complex shear modulus |G*|, elasticity
      Gd and viscosity Gl of SW620 human colorectal cancer xenografts before and 24 h
      after treatment with either 200 mg kg(-1) of the vascular disrupting agent ZD6126
      (N-acetylcolchinol-O-phosphate) or vehicle control, and the data were compared
      with changes in water diffusivity measured by diffusion-weighted magnetic
      resonance imaging. RESULTS: A heterogeneous distribution of |G*|, Gd and Gl was
      observed pre-treatment with an intertumoral coefficient of variation of 13% for
      |G*|. There were no significant changes in the vehicle-treated cohort. In
      contrast, ZD6126 induced a significant decrease in the tumour-averaged |G*|
      (P<0.01), Gd (P<0.01) and Gl (P<0.05), and this was associated with
      histologically confirmed central necrosis. This reduction in tumour
      viscoelasticity occurred at a time when no significant change in tumour apparent
      diffusion coefficient (ADC) was observed. CONCLUSIONS: These data demonstrate
      that MRE can provide early imaging biomarkers for treatment-induced tumour
      necrosis.

PMID- 24569472
TI  - Prognostic value of histopathological regression in 850 neoadjuvantly treated
      oesophagogastric adenocarcinomas.
AB  - BACKGROUND: Recently, histopathological tumour regression, prevalence of signet
      ring cells, and localisation were reported as prognostic factors in neoadjuvantly
      treated oesophagogastric (junctional and gastric) cancer. This exploratory
      retrospective study analyses independent prognostic factors within a large
      patient cohort after preoperative chemotherapy including clinical and
      histopathological factors. METHODS: In all, 850 patients presenting with
      oesophagogastric cancer staged cT3/4 Nany cM0/x were treated with neoadjuvant
      chemotherapy followed by resection in two academic centres. Patient data were
      documented in a prospective database and retrospectively analysed. RESULTS: Of
      all factors prognostic on univariate analysis, only clinical response,
      complications, ypTNM stage, and R category were independently prognostic (P<0.01)
      on multivariate analysis. Tumour localisation and signet ring cells were
      independently prognostic only when investigator-dependent clinical response
      evaluation was excluded from the multivariate model. Histopathological tumour
      regression correlates with tumour grading, Lauren classification, clinical
      response, ypT, ypN, and R categories but was not identified as an independent
      prognostic factor. Within R0-resected patients only surgical complications and
      ypTNM stage were independent prognostic factors. CONCLUSIONS: Only established
      prognostic factors like ypTNM stage, R category, and complications were
      identified as independent prognostic factors in resected patients after
      neoadjuvant chemotherapy. In contrast, histopathological tumour regression was
      not found as an independent prognostic marker.

PMID- 24569473
TI  - Identification of biomarkers for lymph node metastasis in early-stage cervical
      cancer by tissue-based proteomics.
AB  - BACKGROUND: Pelvic lymph node metastasis (PLNM) is the key to determining the
      treatment and prognosis of early-stage cervical cancer (CC, I-IIst). The aim of
      this study was to identify biomarkers for PLNM of CC, I-IIst. METHODS: Two
      dimensional fluorescence difference gel electrophoresis and matrix-assisted laser
      desorption/ionisation-time-of-flight mass spectrometry (MALDI-TOF/TOF MS) were
      used to identify differentially expressed proteins in primary CC, I-IIst tissue
      with (n=8) and without (n=10) PLNM. The expression levels of three differential
      proteins (FABP5, HspB1, and MnSOD) were validated using western blotting and
      immunohistochemistry. An independent cohort of 105 CC, I-IIst patients was
      analysed to assess the correlation of FABP5, HspB1, and MnSOD with
      clinicopathologic factors and clinical outcomes. RESULTS: Forty-one differential
      proteins were identified. Upregulation of FABP5, HspB1, and MnSOD in CC, I-IIst
      with PLNM was confirmed and was significantly correlated with PLNM. FABP5, HspB1,
      and MnSOD were significant predictors of PLNM in univariate analysis. FABP5,
      HspB1, and lymphovascular space invasion (LVSI) were independent predictors of
      PLNM in multivariate analysis. Survival curves indicated that CC, I-IIst patients
      with FABP5, HspB1, and MnSOD upregulation had poor prognosis. CONCLUSIONS: FABP5,
      HspB1, and MnSOD may be potential biomarkers for PLNM of CC, I-IIst and may have
      important roles in the pathogenesis of PLNM.

PMID- 24569474
TI  - Biliverdin's regulation of reactive oxygen species signalling leads to potent
      inhibition of proliferative and angiogenic pathways in head and neck cancer.
AB  - BACKGROUND: In this study, we evaluate whether the use of biliverdin (BV), a
      natural non-toxic antioxidant product of haeme catabolism, can suppress head and
      neck squamous cell carcinoma (HNSCC) cell proliferation and improve the tumour
      survival both in vitro and in vivo. Furthermore, we investigate whether this
      therapeutic outcome relies on BV's potent antioxidant effect on reactive oxygen
      species (ROS)-mediated signalling. METHODS: Two well-characterised HNSCC cell
      lines and a mouse model with human HNSCC were used for this study. In vitro, the
      effect of BV on ROS was assayed. Subsequently, critical regulatory proteins
      involved in growth, antiapoptotic, and angiogenic pathways were investigated by
      western blot analysis. In addition, the antiproliferative effect of BV was also
      evaluated using the clonogenic assay. Moreover, tumour growth inhibition was
      assessed using a mouse model with HNSCC. RESULTS: Biliverdin treatment resulted
      in decreased ROS, leading to suppression of proliferation and angiogenesis
      pathways of HNSCC, significantly decreasing the expression and phosphorylation of
      oncogenic factors such as epidermal growth factor receptor (EGFR),
      phosphorylation of Akt, and expression of angiogenic marker and transcription
      factor, hypoxia-inducible factor1-alpha (HIF1-alpha). Furthermore, this
      downregulation of ROS by BV led to a significant suppression of tumour growth in
      vivo. CONCLUSIONS: Our study demonstrates the efficacy of a novel therapeutic
      approach using BV as an antitumour agent against HNSCC through its effect on
      EGFR/Akt and HIF1-alpha/angiogenesis signal transduction pathways. Our findings
      indicate that BV's inhibitory effect on these tumorigenic pathways relies on its
      antioxidant effect, and may extend its therapeutic potential to other solid
      cancers.

PMID- 24569475
TI  - Tumour expression of leptin is associated with chemotherapy resistance and
      therapy-independent prognosis in gastro-oesophageal adenocarcinomas.
AB  - BACKGROUND: Cytotoxic chemotherapy remains the main systemic therapy for gastro
      oesophageal adenocarcinoma, but resistance to chemotherapy is common, resulting
      in ineffective and often toxic treatment for patients. Predictive biomarkers for
      chemotherapy response would increase the probability of successful therapy, but
      none are currently recommended for clinical use. We used global gene expression
      profiling of tumour biopsies to identify novel predictive biomarkers for
      cytotoxic chemotherapy. METHODS: Tumour biopsies from patients (n=14) with TNM
      stage IB-IV gastro-oesophageal adenocarcinomas receiving platinum-based
      combination chemotherapy were used as a discovery cohort and profiled with
      Affymetrix ST1.0 Exon Genechips. An independent cohort of patients (n=154)
      treated with surgery with or without neoadjuvant platinum combination
      chemotherapy and gastric adenocarcinoma cell lines (n=22) were used for
      qualification of gene expression profiling results by immunohistochemistry. A
      cisplatin-resistant gastric cancer cell line, AGS Cis5, and the oesophageal
      adenocarcinoma cell line, OE33, were used for in vitro validation investigations.
      RESULTS: We identified 520 genes with differential expression (Mann-Whitney U,
      P<0.020) between radiological responding and nonresponding patients. Gene
      enrichment analysis (DAVID v6.7) was used on this list of 520 genes to identify
      pathways associated with response and identified the adipocytokine signalling
      pathway, with higher leptin mRNA associated with lack of radiological response
      (P=0.011). Similarly, in the independent cohort (n=154), higher leptin protein
      expression by immunohistochemistry in the tumour cells was associated with lack
      of histopathological response (P=0.007). Higher leptin protein expression by
      immunohistochemistry was also associated with improved survival in the absence of
      neoadjuvant chemotherapy, and patients with low leptin protein-expressing tumours
      had improved survival when treated by neoadjuvant chemotherapy (P for
      interaction=0.038). In the gastric adenocarcinoma cell lines, higher leptin
      protein expression was associated with resistance to cisplatin (P=0.008), but not
      to oxaliplatin (P=0.988) or 5fluorouracil (P=0.636). The leptin receptor
      antagonist SHLA increased the sensitivity of AGS Cis5 and OE33 cell lines to
      cisplatin. CONCLUSIONS: In gastro-oesophageal adenocarcinomas, tumour leptin
      expression is associated with chemoresistance but a better therapy-independent
      prognosis. Tumour leptin expression determined by immunohistochemistry has
      potential utility as a predictive marker of resistance to cytotoxic chemotherapy,
      and a prognostic marker independent of therapy in gastro-oesophageal
      adenocarcinoma. Leptin antagonists have been developed for clinical use and
      leptin and its associated pathways may also provide much needed novel therapeutic
      targets for gastro-oesophageal adenocarcinoma.

PMID- 24569476
TI  - Structural basis for the prion-like MAVS filaments in antiviral innate immunity.
AB  - Mitochondrial antiviral signaling (MAVS) protein is required for innate immune
      responses against RNA viruses. In virus-infected cells MAVS forms prion-like
      aggregates to activate antiviral signaling cascades, but the underlying
      structural mechanism is unknown. Here we report cryo-electron microscopic
      structures of the helical filaments formed by both the N-terminal caspase
      activation and recruitment domain (CARD) of MAVS and a truncated MAVS lacking
      part of the proline-rich region and the C-terminal transmembrane domain. Both
      structures are left-handed three-stranded helical filaments, revealing specific
      interfaces between individual CARD subunits that are dictated by electrostatic
      interactions between neighboring strands and hydrophobic interactions within each
      strand. Point mutations at multiple locations of these two interfaces impaired
      filament formation and antiviral signaling. Super-resolution imaging of virus
      infected cells revealed rod-shaped MAVS clusters on mitochondria. These results
      elucidate the structural mechanism of MAVS polymerization, and explain how an
      alpha-helical domain uses distinct chemical interactions to form self
      perpetuating filaments. DOI: http://dx.doi.org/10.7554/eLife.01489.001. 

PMID- 24569477
TI  - PTRN-1, a microtubule minus end-binding CAMSAP homolog, promotes microtubule
      function in Caenorhabditis elegans neurons.
AB  - In neuronal processes, microtubules (MTs) provide structural support and serve as
      tracks for molecular motors. While it is known that neuronal MTs are more stable
      than MTs in non-neuronal cells, the molecular mechanisms underlying this
      stability are not fully understood. In this study, we used live fluorescence
      microscopy to show that the C. elegans CAMSAP protein PTRN-1 localizes to puncta
      along neuronal processes, stabilizes MT foci, and promotes MT polymerization in
      neurites. Electron microscopy revealed that ptrn-1 null mutants have fewer MTs
      and abnormal MT organization in the PLM neuron. Animals grown with a MT
      depolymerizing drug caused synthetic defects in neurite branching in the absence
      of ptrn-1 function, indicating that PTRN-1 promotes MT stability. Further, ptrn-1
      null mutants exhibited aberrant neurite morphology and synaptic vesicle
      localization that is partially dependent on dlk-1. Our results suggest that PTRN
      1 represents an important mechanism for promoting MT stability in neurons. DOI:
      http://dx.doi.org/10.7554/eLife.01498.001. 

PMID- 24569478
TI  - Synaptotagmin 7 functions as a Ca2+-sensor for synaptic vesicle replenishment.
AB  - Synaptotagmin (syt) 7 is one of three syt isoforms found in all metazoans; it is
      ubiquitously expressed, yet its function in neurons remains obscure. Here, we
      resolved Ca(2+)-dependent and Ca(2+)-independent synaptic vesicle (SV)
      replenishment pathways, and found that syt 7 plays a selective and critical role
      in the Ca(2+)-dependent pathway. Mutations that disrupt Ca(2+)-binding to syt 7
      abolish this function, suggesting that syt 7 functions as a Ca(2+)-sensor for
      replenishment. The Ca(2+)-binding protein calmodulin (CaM) has also been
      implicated in SV replenishment, and we found that loss of syt 7 was phenocopied
      by a CaM antagonist. Moreover, we discovered that syt 7 binds to CaM in a highly
      specific and Ca(2+)-dependent manner; this interaction requires intact Ca(2+)
      binding sites within syt 7. Together, these data indicate that a complex of two
      conserved Ca(2+)-binding proteins, syt 7 and CaM, serve as a key regulator of SV
      replenishment in presynaptic nerve terminals. DOI:
      http://dx.doi.org/10.7554/eLife.01524.001. 

PMID- 24569479
TI  - Mitochondrial Rab GAPs govern autophagosome biogenesis during mitophagy.
AB  - Damaged mitochondria can be selectively eliminated by mitophagy. Although two
      gene products mutated in Parkinson's disease, PINK1, and Parkin have been found
      to play a central role in triggering mitophagy in mammals, how the pre
      autophagosomal isolation membrane selectively and accurately engulfs damaged
      mitochondria remains unclear. In this study, we demonstrate that TBC1D15, a
      mitochondrial Rab GTPase-activating protein (Rab-GAP), governs autophagosome
      biogenesis and morphology downstream of Parkin activation. To constrain
      autophagosome morphogenesis to that of the cargo, TBC1D15 inhibits Rab7 activity
      and associates with both the mitochondria through binding Fis1 and the isolation
      membrane through the interactions with LC3/GABARAP family members. Another TBC
      family member TBC1D17, also participates in mitophagy and forms homodimers and
      heterodimers with TBC1D15. These results demonstrate that TBC1D15 and TBC1D17
      mediate proper autophagic encapsulation of mitochondria by regulating Rab7
      activity at the interface between mitochondria and isolation membranes. DOI:
      http://dx.doi.org/10.7554/eLife.01612.001. 

PMID- 24569480
TI  - The Caenorhabditis elegans microtubule minus-end binding homolog PTRN-1
      stabilizes synapses and neurites.
AB  - Microtubule dynamics facilitate neurite growth and establish morphology, but the
      role of minus-end binding proteins in these processes is largely unexplored.
      CAMSAP homologs associate with microtubule minus-ends, and are important for the
      stability of epithelial cell adhesions. In this study, we report morphological
      defects in neurons and neuromuscular defects in mutants of the C. elegans CAMSAP,
      ptrn-1. Mechanosensory neurons initially extend wild-type neurites, and
      subsequently remodel by overextending neurites and retracting synaptic branches
      and presynaptic varicosities. This neuronal remodeling can be activated by
      mutations known to alter microtubules, and depends on a functioning DLK-1 MAP
      kinase pathway. We found that PTRN-1 localizes to both neurites and synapses, and
      our results suggest that alterations of microtubule structures caused by loss of
      PTRN-1 function activates a remodeling program leading to changes in neurite
      morphology. We propose a model whereby minus-end microtubule stabilization
      mediated by a functional PTRN-1 is necessary for morphological maintenance of
      neurons. DOI: http://dx.doi.org/10.7554/eLife.01637.001. 

PMID- 24569483
TI  - Advice on drugs for patients with strict dietary beliefs.

PMID- 24569481
TI  - The structure and organization of lanceolate mechanosensory complexes at mouse
      hair follicles.
AB  - In mouse hairy skin, lanceolate complexes associated with three types of hair
      follicles, guard, awl/auchene and zigzag, serve as mechanosensory end organs.
      These structures are formed by unique combinations of low-threshold
      mechanoreceptors (LTMRs), Abeta RA-LTMRs, Adelta-LTMRs, and C-LTMRs, and their
      associated terminal Schwann cells (TSCs). In this study, we investigated the
      organization, ultrastructure, and maintenance of longitudinal lanceolate
      complexes at each hair follicle subtype. We found that TSC processes at hair
      follicles are tiled and that individual TSCs host axonal endings of more than one
      LTMR subtype. Electron microscopic analyses revealed unique ultrastructural
      features of lanceolate complexes that are proposed to underlie
      mechanotransduction. Moreover, Schwann cell ablation leads to loss of LTMR
      terminals at hair follicles while, in contrast, TSCs remain associated with hair
      follicles following skin denervation in adult mice and, remarkably, become re
      associated with newly formed axons, indicating a TSC-dependence of lanceolate
      complex maintenance and regeneration in adults. DOI:
      http://dx.doi.org/10.7554/eLife.01901.001. 

PMID- 24569482
TI  - Atomic model of the F420-reducing [NiFe] hydrogenase by electron cryo-microscopy
      using a direct electron detector.
AB  - The introduction of direct electron detectors with higher detective quantum
      efficiency and fast read-out marks the beginning of a new era in electron cryo
      microscopy. Using the FEI Falcon II direct electron detector in video mode, we
      have reconstructed a map at 3.36 A resolution of the 1.2 MDa F420-reducing
      hydrogenase (Frh) from methanogenic archaea from only 320,000 asymmetric units.
      Videos frames were aligned by a combination of image and particle alignment
      procedures to overcome the effects of beam-induced motion. The reconstructed
      density map shows all secondary structure as well as clear side chain densities
      for most residues. The full coordination of all cofactors in the electron
      transfer chain (a [NiFe] center, four [4Fe4S] clusters and an FAD) is clearly
      visible along with a well-defined substrate access channel. From the rigidity of
      the complex we conclude that catalysis is diffusion-limited and does not depend
      on protein flexibility or conformational changes. DOI:
      http://dx.doi.org/10.7554/eLife.01963.001. 

PMID- 24569484
TI  - Evaluation of feasible timing of elective noncardiac procedure after antiplatelet
      discontinuation in patients treated with antiplatelet agents.
AB  - BACKGROUND: The current standard of care is to delay noncardiac procedure (NCP) 5
      to 7 days after discontinuation of antiplatelet agents (APAs) in patients with
      coronary stents. However, it is often difficult to follow because of concerns
      over stent thrombosis. The point-of-care aspirin/P2Y(12) assay (VerifyNow;
      Accumetrics Inc, San Diego, CA) is useful to evaluate platelet reactivity in
      conjunction with APAs. In this study, we evaluated the feasible timing after
      discontinuation of APAs. METHODS AND RESULTS: Sixty-two patients taking APAs, who
      were scheduled to undergo elective NCP, were enrolled. All patients took either
      aspirin 100 mg or aspirin 100 mg plus clopidogrel 75 mg daily. The aspirin
      reactivity unit (ARU) and P2Y(12)-reactivity unit (PRU) were measured from 0 days
      (day 0, no discontinuation) to as long as 5 days (day 5, 5 days after
      discontinuation) depending on each procedure schedule. For 15 patients, baseline
      ARU and PRU (592 and 288) before aspirin/clopidogrel loading at index
      percutaneous coronary intervention were collected as control. For ARU after
      discontinuation of APA, days 0 to 5 values progressively increased over time
      (489.4 T 85.3, 512.6 T 77.0, 589.9 T 58.8, 613.6 T 47.3, 632.6 T 49.2, 662.0 T
      4.2). Likewise, for PRUs, days 0 to 5 values also increased over time (245.0 T
      96.9, 253.9 T 80.9, 270.9 T 45.8, 289.0 T 68.6, 306.5 T 29.2, 351.0 T 8.5). The
      ARU and PRU well correlated with days after APA discontinuation by linear
      regression analysis ( y = 490.897 + 39.238 * x, R(2) = 0.43, P G 0.001; y =
      241.739 + 16.701 * x, R(2) = 0.092, P = 0.018, respectively). Assuming baseline
      ARU and PRU as 592 and 288, the mean days after complete reversal of platelet
      reactivity by APAs are 2.6 and 2.8, respectively. CONCLUSIONS: The feasible
      timing of NCP after discontinuation of APAs showed less than 5 days. VerifyNow is
      useful in the evaluation of antiplatelet reversal after discontinuation of APAs.
      .

PMID- 24569485
TI  - Intensive therapy in newly diagnosed type 2 diabetes: results of a 6-year
      randomized trial.
AB  - BACKGROUND: This study aimed to assess the efficacy of early intensive diabetes
      therapy with either insulin plus metformin (INS) or triple oral therapy (TOT)
      with metformin, glyburide, and pioglitazone on glycemic control and A-cell
      function. METHODS: Fifty-eight treatment-naive newly diagnosed patients with type
      2 diabetes underwent a 3-month lead-in treatment period with insulin and
      metformin, then were randomized to INS or TOT for 6 years. beta-Cell function was
      measured using mixed-meal challenge test. beta-Cell function remained stable
      throughout the 6-year study in both groups, as measured by the C-peptide area
      under the curve (AUC; P = 0.13), the AUC C-peptide/AUC glucose (P = 0.9), and by
      the disposition index (P = 0.8). Excellent glycemic control was maintained in
      both groups (end-of-study hemoglobinA1c, 7.3% [SD, 1.7%] INS vs 6.4% [1.4%] TOT;
      P = 0.4). There were 8 treatment failures (confirmed hemoglobinA1c, 98%) in INS
      and 6 in TOT (P = 0.93). The predictors of treatment failure included higher
      fasting glucose (P = 0.008), fasting C-peptide (P = 0.008), systolic blood
      pressure (P = 0.004), and lower insulin sensitivity (P = 0.04) at randomization.
      CONCLUSIONS: Early intensive treatment at the time of type 2 diabetes diagnosis
      initial short-term insulin treatment followed by either insulin-based or
      intensive oral hypoglycemic-based therapy-stabilizes beta-cell function for at
      least 6 years. Treatment failure was independent of intervention and was
      associated with worse disease pathology at baseline.

PMID- 24569486
TI  - A plant factory for moth pheromone production.
AB  - Moths depend on pheromone communication for mate finding and synthetic pheromones
      are used for monitoring or disruption of pheromone communication in pest insects.
      Here we produce moth sex pheromone, using Nicotiana benthamiana as a plant
      factory, by transient expression of up to four genes coding for consecutive
      biosynthetic steps. We specifically produce multicomponent sex pheromones for two
      species. The fatty alcohol fractions from the genetically modified plants are
      acetylated to mimic the respective sex pheromones of the small ermine moths
      Yponomeuta evonymella and Y. padella. These mixtures are very efficient and
      specific for trapping of male moths, matching the activity of conventionally
      produced pheromones. Our long-term vision is to design tailor-made production of
      any moth pheromone component in genetically modified plants. Such semisynthetic
      preparation of sex pheromones is a novel and cost-effective way of producing
      moderate to large quantities of pheromones with high purity and a minimum of
      hazardous waste. 

PMID- 24569487
TI  - Sensory systems: the hungry sense.

PMID- 24569489
TI  - Microwave assisted base dependent regioselective synthesis of partially reduced
      chromenes, isochromenes and phenanthrenes.
AB  - We have reported a microwave assisted base directed regioselective synthesis of
      partially reduced chromenes, isochromenes and phenanthrenes. Functionalized 4
      (piperidin-1-yl)-5,6-dihydro-2H-benzo[h]-chromen-2-one-3-carbonitriles have been
      used as precursors, which on reaction with functionalized acetophenones in the
      presence of KOH in DMF under microwave irradiation yield (Z)-2-(2-aryl-5,6
      dihydro-4H-benzo[f]isochromen-4-ylidene)acetonitriles. The use of NaH in DMF
      provides 3-aryl-1-(piperidin-1-yl)-9,10-dihydro phenanthrene-2-carbonitriles in
      excellent yield regioselectively. The use of cyclohexanone as a nucleophile
      source yields (Z)-2-(3,4,7,8-tetrahydro-1H-naphtho[2,1-c]chromen-6(2H)
      ylidene)acetonitriles. The structure and geometry of isochromene have been proved
      without any ambiguity by single crystal X-ray diffraction. 

PMID- 24569491
TI  - Musculocutaneous nerve injury in a high school pitcher.
AB  - : Nontraumatic musculocutaneous nerve palsy is a rare injury that can occur in
      throwers. We present a case of musculocutaneous nerve injury in a high school
      pitcher, which has rarely been previously reported. The unique electromyography
      findings add to the overall spectrum seen with musculocutaneous nerve injuries in
      throwers. Sensory abnormalities may not be present at initial evaluation, but
      rather weakness or pain of the biceps is the most common presenting concern.
      Electrodiagnostic evaluation is paramount for confirmation of diagnosis, yet the
      timing of this study is critical for its accuracy. Rest and progressive physical
      therapy remain as the current treatment of choice. Resolution of symptoms,
      although time consuming, is complete in the majority of cases, including ours. 

PMID- 24569490
TI  - Choroidal lymphoma shows calm, rippled, or undulating topography on enhanced
      depth imaging optical coherence tomography in 14 eyes.
AB  - PURPOSE: To describe the features of choroidal lymphoma on enhanced depth imaging
      optical coherence tomography. METHODS: This retrospective observational case
      series included 14 eyes of 13 patients, with choroidal lymphoma, studied by
      enhanced depth imaging optical coherence tomography. RESULTS: The mean age at
      presentation was 63 years (median, 65 years; range, 32-87 years). Systemic
      lymphoproliferative disease was present in 2 cases as non-Hodgkin lymphoma (n =
      1) or Waldenstrom macroglobulinemia (n = 1). On clinical examination, the
      choroidal infiltrate was classified as unifocal (n = 3), multifocal (n = 4), or
      diffuse (n = 7). Enhanced depth imaging optical coherence tomography scans
      through the tumor epicenter revealed infiltration of the choroid with apparent
      inward compression of choroidal vascular structures, creating an anterior tumor
      surface topography that appeared smooth (calm) (n = 7), mini-wavy (rippled) (n =
      2), or maxi-wavy (undulating) (n = 5). Greater tumor thickness correlated with
      increasing tumor surface fluctuation as calm was mean 1.7mm, rippled was 2.8 mm,
      and undulating surface was 4.1 mm in ultrasonographic thickness. On enhanced
      depth imaging optical coherence tomography, the mean subfoveolar choroidal
      thickness, measurable in 9 eyes, was 484 MUm (median, 423 MUm; range, 156-1,002
      MUm) (81% greater) versus 267 MUm (median, 276 MUm; range, 142-501 MUm) in the
      unaffected eye. The mean maximal tumor thickness, measurable in 8 eyes, was 117%
      greater at 602 MUm (median, 538 MUm; range, 241-966 MUm) compared with the
      corresponding unaffected choroid in the contralateral eye at 278 MUm (median, 245
      MUm; range, 189-511 MUm) (P = 0.046). Inability to measure choroidal thickness
      was due to dense tumor-induced optical shadowing with inability to visualize the
      sclerochoroidal junction (P = 0.009). There was no visible infiltration into the
      overlying retina in any case. CONCLUSION: Enhanced depth imaging optical
      coherence tomography of choroidal lymphoma revealed 1 of 3 surface topographical
      patterns resembling an ocean as calm (n = 7), rippled (n = 2), or undulating (n =
      5), correlating with increasing tumor thickness.

PMID- 24569488
TI  - The log-dynamic brain: how skewed distributions affect network operations.
AB  - We often assume that the variables of functional and structural brain parameters 
      such as synaptic weights, the firing rates of individual neurons, the
      synchronous discharge of neural populations, the number of synaptic contacts
      between neurons and the size of dendritic boutons - have a bell-shaped
      distribution. However, at many physiological and anatomical levels in the brain,
      the distribution of numerous parameters is in fact strongly skewed with a heavy
      tail, suggesting that skewed (typically lognormal) distributions are fundamental
      to structural and functional brain organization. This insight not only has
      implications for how we should collect and analyse data, it may also help us to
      understand how the different levels of skewed distributions - from synapses to
      cognition - are related to each other. 

PMID- 24569492
TI  - Injury pathology at the time of anterior cruciate ligament reconstruction
      associations with self-assessment of knee function.
AB  - OBJECTIVE: To evaluate the association of preoperative Knee Injury and
      Osteoarthritis Outcome Score (KOOS) and structural injuries reported at the time
      of anterior cruciate ligament reconstruction (ACLR). DESIGN: Cross-sectional
      study. SETTING: Three medical centers in California. PARTICIPANTS: Primary ACLRs
      (N = 636) performed between January 2009 and June 2010. INDEPENDENT VARIABLES:
      The 5 KOOS subscales: pain, other symptoms, activities of daily living (ADL),
      function in sport and recreation (Sport/Rec), and quality of life (QoL). MAIN
      OUTCOME MEASURES: Associated injuries (cartilage, medial meniscus, lateral
      meniscus, other ligaments), identified at the time of ACLR. RESULTS: Sixty-eight
      percent of the cohort was male and the median age was 26 years. No gender
      differences in KOOS were observed. No KOOS differences were observed by race,
      except in Sport/Rec. Younger patients reported higher KOOS. Pain and ADL scores
      were not associated with any concurrent injury. A 10-point increase in KOOS
      symptoms subscale was associated with 22% higher likelihood of isolated ACL, 13%
      lower likelihood of medial meniscus injury, and 10% lower likelihood of lateral
      meniscus. A 10-point increase in the KOOS Sport/Rec subscale score was associated
      with 8% higher likelihood of isolated ACL and 9% lower likelihood of medial
      meniscus injury. A 10-point increase in the KOOS QoL subscale was associated with
      15% lower likelihood of medial meniscus injury. CONCLUSIONS: Weak associations
      between the symptoms, Sports/Rec, and QoL subscales and structural injuries at
      ACLR were observed. The KOOS and its subscales are not useful as indicators of
      the pattern or severity of preoperative injury of patients presenting for ACLR.

PMID- 24569493
TI  - A new modified cytosine base capable of base pairing with guanine using four
      hydrogen bonds.
AB  - Oligonucleotides, containing 4-N-(1H-pyrrol-2-ylcarbonyl)deoxycytidine (dC(Pyc))
      and related derivatives, were synthesized via deprotection using 1.5 M
      NaOMe/MeOH. Among them, oligodeoxynucleotides containing dC(Pyc) exhibited a
      higher hybridization affinity for DNA and RNA than the unmodified
      oligodeoxynucleotides. Comparative analysis between dC(Pyc) and its derivatives
      by molecular dynamic simulation indicated that the C(Pyc) residue could form four
      hydrogen bonds with the opposite G nucleobase keeping a more planar structure
      than the C(Inc) residue where the Pyc group was replaced with a 1H-indol-2
      ylcarbonyl group. 

PMID- 24569494
TI  - Ab initio and semi-empirical Molecular Dynamics simulations of chemical reactions
      in isolated molecules and in clusters.
AB  - Recent progress in "on-the-fly" trajectory simulations of molecular reactions,
      using different electronic structure methods is discussed, with analysis of the
      insights that such calculations can provide and of the strengths and limitations
      of the algorithms available. New developments in the use of both ab initio and
      semi-empirical electronic structure algorithms are described. The emphasis is on:
      (i) calculations of electronic properties along the reactive trajectories and the
      unique insights this can contribute to the processes; (ii) electronic structure
      methods recently introduced to this topic to improve accuracy, extend
      applicability or enhance computational efficiency. The methods are presented with
      examples, including new results, of reactions of both isolated molecules and of
      molecules in media, mostly clusters. Possible future directions for this fast
      growing field are suggested. 

PMID- 24569495
TI  - Metzincins and related genes in experimental renal ageing: towards a unifying
      fibrosis classifier across species.
AB  - BACKGROUND: We have previously described a transcriptomic classifier consisting
      of metzincins and related genes (MARGS) discriminating kidneys and other organs
      with or without fibrosis from human biopsies. We now apply our MARGS-based
      algorithm to a rat model of age-associated interstitial renal fibrosis. METHODS:
      Untreated Fisher 344 rats (n = 76) were sacrificed between 2 to 104 weeks of age.
      For gene expression studies, we used single colour (Cy3) Agilent Whole Rat Genome
      4 * 44k microarrays; 4-5 animals of each sex were profiled at each of the
      following ages: 2, 5, 6, 8, 15, 21, 78 and 104 weeks. Intensity data were
      subjected to variance stabilization (www.Partek.com). Data were analysed with
      ANOVA and other statistical methods. RESULTS: Sixty MARGS were differentially
      expressed across age groups. More MARGS were differentially expressed in older
      males than in older females. Principal component analysis showed gene expression
      induced segregation of age groups by sex from 6 to 104 weeks of age. The
      expression level of MMP7 correlated best with fibrosis grade. Severity of
      fibrosis was determined in 20 animals at 78 and 104 weeks of age. Expression
      values of 15 of 19 genes of the original classifier present on the Agilent array,
      in conjunction with linear discriminant analysis, was sufficient to correctly
      classify these 20 samples into non-fibrosis and fibrosis. Overrepresentation of
      MMP2 protein and CD44 protein in fibrosis was confirmed by immunofluorescence.
      CONCLUSIONS: Based on these results and our previous work, the MARGS classifier
      represents a cross-organ and cross-species classifier of fibrosis irrespective of
      aetiology. This finding provides evidence for a common pathway leading to
      fibrosis and will help to design a PCR-based clinical test.

PMID- 24569497
TI  - Simplified phosphorus kinetic modeling: predicting changes in predialysis serum
      phosphorus concentration after altering the hemodialysis prescription.
AB  - BACKGROUND: The KDIGO work group recommends increasing dialytic phosphorus
      removal in Stage 5D chronic kidney disease patients with persistent
      hyperphosphatemia; however, optimal prescriptions to enhance phosphorus removal
      by hemodialysis (HD) therapies have not yet been established. This study
      evaluated whether phosphorus kinetic modeling based on a pseudo one-compartment
      model could provide practical clinical guidance for predicting changes in
      predialysis serum phosphorus concentration after altering the HD prescription.
      METHODS: Patient-specific phosphorus kinetic parameters determined from thrice
      weekly HD treatments on 774 patients in the HEMO Study were used to predict
      changes in predialysis serum phosphorus concentration after altering the HD
      prescription from thrice weekly to short daily and long nocturnal HD therapies.
      The effect of changes in the oral phosphorus binder prescription on predicted
      changes in the predialysis serum phosphorus concentration was also illustrated
      using the concept of equivalent phosphorus binder dose. RESULTS: Decreases in
      predialysis serum phosphorus concentration from thrice weekly HD to short daily
      and long nocturnal HD prescriptions demonstrated strong associations with the
      predialysis serum phosphorus concentration during thrice weekly HD that were
      relatively independent of patient-specific phosphorus kinetic parameters. Thus,
      the percent decrease in predialysis serum phosphorus concentration was
      approximately the same among patients for a given alteration in the HD
      prescription. Both increased weekly treatment time and frequency resulted in a
      reduction in the predialysis serum phosphorus concentration; however, the effect
      of treatment time was more influential. Simultaneous reduction in the effective
      phosphorus binder dose blunted the decrease in the predialysis serum phosphorus
      concentration. CONCLUSIONS: This study demonstrated that a simplified form of
      phosphorus kinetic modeling based on a pseudo one-compartment model can provide
      practical clinical guidance for predicting changes in predialysis serum
      phosphorus concentration after altering the HD prescription. Prospective
      validation of this approach in future studies is warranted.

PMID- 24569496
TI  - Clinical practice guideline on diagnosis and treatment of hyponatraemia.
AB  - Hyponatraemia, defined as a serum sodium concentration <135 mmol/l, is the most
      common disorder of body fluid and electrolyte balance encountered in clinical
      practice. It can lead to a wide spectrum of clinical symptoms, from subtle to
      severe or even life threatening, and is associated with increased mortality,
      morbidity and length of hospital stay in patients presenting with a range of
      conditions. Despite this, the management of patients remains problematic. The
      prevalence of hyponatraemia in widely different conditions and the fact that
      hyponatraemia is managed by clinicians with a broad variety of backgrounds have
      fostered diverse institution- and speciality-based approaches to diagnosis and
      treatment. To obtain a common and holistic view, the European Society of
      Intensive Care Medicine (ESICM), the European Society of Endocrinology (ESE) and
      the European Renal Association - European Dialysis and Transplant Association
      (ERA-EDTA), represented by European Renal Best Practice (ERBP), have developed
      the Clinical Practice Guideline on the diagnostic approach and treatment of
      hyponatraemia as a joint venture of three societies representing specialists with
      a natural interest in hyponatraemia. In addition to a rigorous approach to
      methodology and evaluation, we were keen to ensure that the document focused on
      patient-important outcomes and included utility for clinicians involved in
      everyday practice. 

PMID- 24569498
TI  - How can genetics and epigenetics help the nephrologist improve the diagnosis and
      treatment of chronic kidney disease patients?
AB  - Discovery of novel improved tools for diagnosis, prevention and therapy of
      chronic kidney disease (CKD) is an important task for the nephrology community
      and it is likely that scientific breakthroughs, to a large extent, will be based
      on genomics. The rapid growth of the number of genome-wide association studies,
      major advances in DNA sequencing and omics profiling, and accelerating biomedical
      research efforts in this area have greatly expanded the knowledge base needed for
      applied genomics. However, translating and implementing genotype-phenotype data
      into gene-based medicine in CKD populations is still in an early phase and will
      require continuous research efforts with integrated approaches and intensified
      investigations that focus on the biological pathways, which causatively link a
      genetic variant with the disease phenotype. In this article, we review some
      current strategies to unravel these translational gaps as well as prospects for
      the implementation of genetic and epigenetic methods into novel clinical
      practice. 

PMID- 24569500
TI  - New to Galleria mellonella: modeling an ExPEC infection.

PMID- 24569499
TI  - Oral administration of inosine produces antidepressant-like effects in mice.
AB  - Inosine, a breakdown product of adenosine, has recently been shown to exert
      immunomodulatory and neuroprotective effects. We show here that the oral
      administration of inosine has antidepressant-like effects in two animal models.
      Inosine significantly enhanced neurite outgrowth and viability of primary
      cultured neocortical neurons, which was suppressed by adenosine A1 and A2A
      receptor agonists. Oral administration of inosine to mice transiently increased
      its concentration in the brain and enhanced neuronal proliferation in the dentate
      gyrus, accompanied by phosphorylation of mitogen-activated protein kinase and
      increase in transcript level of brain-derived neurotrophic factor. In stress
      models, oral inosine prevented an increase in immobility time in forced swim test
      after chronically unexpected stress and mitigated a reduction in sucrose
      preference after chronic social defeat stress. These results indicate that oral
      administration of inosine has the potential to prevent depressive disorder via
      adenosine receptors. 

PMID- 24569502
TI  - Lessons from Scotland's experience of alcohol pricing.

PMID- 24569503
TI  - Atmospheric aqueous phase radical chemistry of the isoprene oxidation products
      methacrolein, methyl vinyl ketone, methacrylic acid and acrylic acid--kinetics
      and product studies.
AB  - Kinetic and mechanistic studies were conducted on the isoprene oxidation products
      methacrolein, methyl vinyl ketone, methacrylic and acrylic acid reacting with
      hydroxyl and nitrate radicals and sulfate radical anions in aqueous solution by
      use of the laser flash photolysis technique and a reversed-rate method for
      kinetics. High-performance liquid chromatography/mass spectrometry was applied
      for product analysis. The kinetic investigations show the highest reactivity of
      the hydroxyl radical followed by sulfate and nitrate radicals. For methacrolein
      and methyl vinyl ketone the following rate constants have been determined at 298
      K: k(OH+methacrolein) = (9.4 +/- 0.7) * 10(9) M(-1) s(-1), k(OH+methyl vinyl
      ketone) = (7.3 +/- 0.5) * 10(9) M(-1) s(-1), k(NO3+methacrolein) = (4.0 +/- 1.0)
      * 10(7) M(-1) s(-1), k(NO3+methyl vinyl ketone) = (9.7 +/- 3.4) * 10(6) M(-1) s(
      1), k(SO4(-)+methacrolein) = (9.9 +/- 4.9) * 10(7) M(-1) s(-1) and k(SO4(
      )+methyl vinyl ketone) = (1.0 +/- 0.2) * 10(8) M(-1) s(-1). Temperature and pH
      dependencies of the reactions of OH, NO3 and SO4(-) with methacrolein, methyl
      vinyl ketone, methacrylic and acrylic acid as well as Arrhenius parameters have
      been obtained and discussed. Product studies were performed on the OH radical
      induced oxidation of methacrolein and methyl vinyl ketone. In the reaction of
      methacrolein + OH methylglyoxal and hydroxyacetone were identified as first
      oxidation products with yields of 0.099 and 0.162. Methylglyoxal was primarily
      produced in the oxidation of methyl vinyl ketone with a yield of 0.052. For both
      precursor compounds the formation of glycolaldehyde was observed for the first
      time with yields of 0.051 and 0.111 in the oxidation of methacrolein and methyl
      vinyl ketone, respectively. Furthermore, highly functionalised C4 compounds were
      determined from the oxidation of both precursor compounds, but for the first time
      for methyl vinyl ketone. Reaction schemes were developed based on known peroxyl
      radical reaction mechanisms. The aqueous phase conversion of the first generation
      isoprene oxidation products can potentially contribute to tropospheric aqueous
      phase budgets of important carbonyl and dicarbonyl components which are expected
      to be conducive to the formation of aqSOA. 

PMID- 24569501
TI  - Cell segregation in the vertebrate hindbrain relies on actomyosin cables located
      at the interhombomeric boundaries.
AB  - Segregating cells into compartments during embryonic development is essential for
      growth and pattern formation. Physical mechanisms shaping compartment boundaries
      were recently explored in Drosophila, where actomyosin-based barriers were
      revealed to be important for keeping cells apart. In vertebrates, interhombomeric
      boundaries are straight interfaces, which often serve as signaling centers that
      pattern the surrounding tissue. Here, we demonstrate that in the hindbrain of
      zebrafish embryos cell sorting sharpens the molecular boundaries and, once
      borders are straight, actomyosin barriers are key to keeping rhombomeric cells
      segregated. Actomyosin cytoskeletal components are enriched at interhombomeric
      boundaries, forming cable-like structures in the apical side of the
      neuroepithelial cells by the time morphological boundaries are visible. When
      myosin II function is inhibited, cable structures do not form, leading to
      rhombomeric cell mixing. Downregulation of EphA4a compromises actomyosin cables
      and cells with different rhombomeric identity intermingle, and the phenotype is
      rescued enhancing myosin II activity. Moreover, enrichment of actomyosin
      structures is obtained when EphA4 is ectopically expressed in even-numbered
      rhombomeres. These findings suggest that mechanical barriers act downstream of
      EphA/ephrin signaling to segregate cells from different rhombomeres. 

PMID- 24569504
TI  - Geriatric ECT at a Turkish teaching hospital: a 5-year experience.

PMID- 24569505
TI  - Low titer group O whole blood in emergency situations.
AB  - In past and ongoing military conflicts, the use of whole blood (WB) as a
      resuscitative product to treat trauma-induced shock and coagulopathy has been
      widely accepted as an alternative when availability of a balanced component-based
      transfusion strategy is restricted or lacking. In previous military conflicts,
      ABO group O blood from donors with low titers of anti-A/B blood group antibodies
      was favored. Now, several policies demand the exclusive use of ABO group-specific
      WB. In this short review, we argue that the overall risks, dangers, and
      consequences of "the ABO group-specific approach," in emergencies, make the use
      of universal group O WB from donors with low titers of anti-A/B safer. Generally,
      risks with ABO group-specific transfusions are associated with in vivo
      destruction of the red blood cells transfused. The risk with group O WB is from
      the plasma transfused to ABO-incompatible patients. In the civilian setting, the
      risk of clinical hemolytic transfusion reactions (HTRs) due to ABO group-specific
      red blood cell transfusions is relatively low (approximately 1:80,000), but the
      consequences are frequently severe. Civilian risk of HTRs due to plasma
      incompatible transfusions, using titered donors, is approximately 1:120,000 but
      usually of mild to moderate severity. Emergency settings are often chaotic and
      resource limited, factors well known to increase the potential for human errors.
      Using ABO group-specific WB in emergencies may delay treatment because of needed
      ABO typing, increase the risk of clinical HTRs, and increase the severity of
      these reactions as well as increase the danger of underresuscitation due to lack
      of some ABO groups. When the clinical decision has been made to transfuse WB in
      patients with life-threatening hemorrhagic shock, we recommend the use of group O
      WB from donors with low anti-A/B titers when logistical constraints preclude the
      rapid availability of ABO group-specific WB and reliable group matching between
      donor and recipient is not feasible. 

PMID- 24569506
TI  - Phosphodiesterase 4 inhibition dose dependently stabilizes microvascular barrier
      functions and microcirculation in a rodent model of polymicrobial sepsis.
AB  - BACKGROUND: Breakdown of microvascular endothelial barrier functions contributes
      to disturbed microcirculation, organ failure, and death in sepsis. Increased
      endothelial cAMP levels by systemic application of phosphodiesterase 4 inhibitors
      (PD-4-I) have previously been demonstrated to protect microvascular barrier
      properties in a model of systemic inflammation (systemic inflammatory response
      syndrome) suggesting a novel therapeutic option to overcome this problem.
      However, in a clinically relevant model of polymicrobial sepsis long-term
      effects, immunomodulatory effects and effectivity of PD-4-I to stabilize
      microvascular barrier functions and microcirculation remained unexplored.
      METHODS: We induced polymicrobial sepsis using the colon ascendens stent
      peritonitis (CASP) model in which we performed macrohemodynamic and
      microhemodynamic monitoring with and without systemic intravenous application of
      different doses of PD-4-I rolipram in Sprague-Dawley rats over 26 h. RESULTS: All
      animals with CASP showed clinical and laboratory signs of sepsis and peritonitis.
      Whereas macrohemodynamic adverse effects were not evident, application of PD-4-I
      led to stabilization of endothelial barrier properties as revealed by reduced
      extravasation of fluorescein isothiocyanate-albumin. However, only low-dose
      application of 1 mg/kg body weight per hour of PD-4-I improved microcirculatory
      flow in the CASP model, whereas high-dose therapy of 3 mg/kg BW per hour PDI-4-I
      had adverse effects. Accordingly, sepsis-induced acute kidney injury and lung
      edema were prevented by PD-4-I treatment. Furthermore, PD-4-I showed
      immunomodulatory effects as revealed by decreased interleukin 1alpha (IL-1alpha),
      IL-1beta, IL-12, and tumor necrosis factor alpha levels following PD-4-I
      treatment, which appeared not to correlate with barrier-stabilizing effects of
      rolipram. CONCLUSIONS: These data provide further evidence that systemic
      application of PD-4-I could be suitable for therapeutic microvascular barrier
      stabilization and improvement of microcirculatory flow in sepsis.

PMID- 24569508
TI  - Impact of endotoxin challenge in obese pigs.
AB  - Studies exploring the influence of obesity on septic shock remain limited and
      controversial. Pigs were chosen as a clinically relevant species, resembling to
      humans in various functions. We hypothesize obesity may impair porcine acute
      endotoxic shock. Four groups of five "Yucatan" minipigs were studied: lean and
      obese control groups, lean lipopolysaccharide (LPS) group receiving Escherichia
      coli endotoxin (LPS) and obese LPS group receiving the same endotoxin dose. We
      measured hemodynamic and oxygenation parameters, skin microvascular blood flow at
      rest and during reactive hyperemia, von Willebrand factor, tumor necrosis factor
      alpha, and interleukin 6. All measurements were performed at baseline and at 30,
      60, 90, 150, and 300 min. Results were given as median with 25th to 75th
      interquartile range. Control groups remained stable during the study period. In
      LPS groups, administration of endotoxin resulted in a typical hypokinetic shock.
      In obese LPS group at 300 min, we observed a significant impairment of cardiac
      index (1.2 [1.06-1.45] vs. 1.7 [1.57-1.97] L/min per m, P = 0.008) compared with
      the lean LPS group; moreover, pulmonary hypertension (mean arterial pressure: 42
      [39-47] vs. 32 [28-34] mmHg, P = 0.008), hypoxemia (partial pressure of oxygen:
      216 [178-262] vs. 325 [285-414] mmHg, P = 0.02), and lactate levels (5.8 [4.2
      6.8] vs. 3.9 [2.2-5.5] mmol/L, P = 0.04) were significantly higher compared with
      the lean LPS group. Throughout the study, rest flow and peak flow during reactive
      hyperemia were more decreased in the obese LPS group. Compared with the lean LPS
      group, tumor necrosis factor alpha levels at 60 min (269 [178-428] vs. 126 [105
      166] ng/mL, P = 0.03) and interleukin 6 levels at 300 min (101 [61-142] vs. 52
      [36-64] ng/mL, P = 0.03) were significantly higher in the obese LPS group. In our
      model of endotoxic shock, obese pigs developed a more severe hemodynamic failure
      with pronounced microcirculatory dysfunction and proinflammatory response. 

PMID- 24569507
TI  - Coagulopathy after severe pediatric trauma.
AB  - Trauma remains the leading cause of morbidity and mortality in the United States
      among children aged 1 to 21 years. The most common cause of lethality in
      pediatric trauma is traumatic brain injury. Early coagulopathy has been commonly
      observed after severe trauma and is usually associated with severe hemorrhage
      and/or traumatic brain injury. In contrast to adult patients, massive bleeding is
      less common after pediatric trauma. The classical drivers of trauma-induced
      coagulopathy include hypothermia, acidosis, hemodilution, and consumption of
      coagulation factors secondary to local activation of the coagulation system after
      severe traumatic injury. Furthermore, there is also recent evidence for a
      distinct mechanism of trauma-induced coagulopathy that involves the activation of
      the anticoagulant protein C pathway. Whether this new mechanism of posttraumatic
      coagulopathy plays a role in children is still unknown. The goal of this review
      is to summarize the current knowledge on the incidence and potential mechanisms
      of coagulopathy after pediatric trauma and the role of rapid diagnostic tests for
      early identification of coagulopathy. Finally, we discuss different options for
      treating coagulopathy after severe pediatric trauma. 

PMID- 24569512
TI  - Sphygmomanometer cuffs: a potential source of infection!
AB  - We evaluated the potential pathogenic hazard of sphygmomanometer blood pressure
      cuffs (BPCs) in a hospital setting. Prospectively, the presence of bacterial
      organisms on 120 BPCs in 14 medical wards and outpatient clinics in a district
      general hospital in London was assessed. Swabs taken from the inner aspect of the
      cuffs were cultured using standard microbiological techniques. Bacterial
      organisms were found in 85% (102) of the 120 BPCs assessed. The highest rates of
      contamination were found in the outpatients department (90%). There were
      differences in the most common bacterial species isolated between the samples
      obtained from the outpatient clinics and the wards, with coagulase-negative
      Staphylococcus and diphtheroids being the most prevalent species in the wards and
      outpatient clinics, respectively. These findings highlight the necessity to
      eliminate this potential risk of infection. 

PMID- 24569511
TI  - The origin of the bifurcated axial skeletal system in the twin-tail goldfish.
AB  - Twin-tail goldfish possess a bifurcated caudal axial skeleton. The scarcity of
      this trait in nature suggests that a rare mutation, which drastically altered the
      mechanisms underlying axial skeleton formation, may have occurred during goldfish
      domestication. However, little is known about the molecular development of twin
      tail goldfish. Here we show that the bifurcated caudal skeleton arises from a
      mutation in the chordin gene, which affects embryonic dorsal-ventral (DV)
      patterning. We demonstrate that formation of the bifurcated caudal axial skeleton
      requires a stop-codon mutation in one of two recently duplicated chordin genes;
      this mutation may have occurred within approximately 600 years of domestication.
      We also report that the ventral tissues of the twin-tail strain are enlarged, and
      form the embryonic bifurcated fin fold. However, unlike previously described
      chordin-deficient embryos, this is not accompanied by a reduction in anterior
      dorsal neural tissues. These results provide insight into large-scale evolution
      arising from artificial selection. 

PMID- 24569513
TI  - Mechanical approach in the management of advanced acute and chronic heart
      failure: the state of the art.
AB  - Despite the progress in medical therapy, advanced heart failure (AHF) remains a
      global epidemic with high morbidity and mortality. Novel cardiac support
      strategies such as pharmacologic agents, mechanical circulatory support (MCS),
      and cell- or matrix-based therapies are promising for these patients. The
      indications, types, and timing of MCS implantation depend to a large extent on
      the presentation, clinical status of the patient, underlying etiology, and long
      term prospects. The presence or absence of end-organ damage has a significant
      impact on prognosis following MCS initiation. Although many patients with acute
      AHF may have end-organ damage, their prospect of recovery, once appropriate
      therapy is instituted, is better than for patients who had AHF for longer periods
      of time. We consider the multidisciplinary approaches used for the management of
      AHF and the novel cardiac support strategies (eg, MCS). Appropriate selection of
      patient, device, time, and end point is essential for better outcomes. 

PMID- 24569514
TI  - Carotid artery stenting improves cerebral hemodynamics regardless of the flow
      direction of ophthalmic artery.
AB  - We enrolled 221 patients with elective carotid artery stenting (CAS). Patients
      with contralateral carotid stenosis exceeding 50%, insufficient vertebral artery
      (VA) flows, or angioplasty at subclavian artery were excluded. All patients
      underwent serial cerebral ultrasound studies. Of the 116 included patients, the
      direction of ophthalmic artery (OA) flow was forward in 74 patients while
      reversed in 42. The reversed flow group had worse ipsilateral stenosis, higher
      hemoglobin, and cardiac output. After CAS, the reversed flow group had an
      immediate recovery of ipsilateral internal carotid artery flow volume (FV; P <
      .0001), time average velocity (TAV) of middle cerebral artery (P = .02), and
      normalization of OA flow. The forward flow group had gradual decrement in TAV of
      contralateral anterior cerebral artery (P = .01) and total FV of VA (P = .001).
      Our results suggest CAS improves cerebral hemodynamics through different ways
      regardless of the direction of OA flow. 

PMID- 24569510
TI  - Toll-like receptor 4 plays a central role in cardiac dysfunction during trauma
      hemorrhage shock.
AB  - Cardiac dysfunction is a major consequence that contributes to the high mortality
      of trauma-hemorrhage (TH) patients. Recent evidence suggests that innate immune
      and inflammatory responses mediated by Toll-like receptors (TLRs) play a critical
      role in the pathophysiologic mechanisms of acute organ dysfunction during TH.
      This study investigated the role of TLR4 in cardiac dysfunction following TH.
      Toll-like receptor 4-deficient (TLR4-/-, n = 7/group) and age-matched wild-type
      (WT, n = 8/group) mice were subjected to TH that was induced by soft tissue
      injury and blood withdrawal from the jugular vein to a mean arterial pressure of
      35 +/- 5 mmHg. Cardiac function and mean arterial pressure were measured with a
      Millar system before, during, and after blood withdrawal. Sham surgical-operated
      mice served as control (WT, n = 9/group; TLR4-/-, n = 10/group). Cardiac function
      in WT mice was significantly reduced following TH. However, cardiac function was
      well preserved in TLR4-/- mice. Administration of a TLR4 antagonist (3 mg/kg) to
      WT mice also significantly attenuated TH-induced cardiac dysfunction. Western
      blot showed that either TLR4-/- or TLR4 antagonist markedly attenuated TH-induced
      decreases in the levels of phosphorylated-Akt in myocardium. In addition,
      inhibition of TLR4 attenuated TH-induced myocardial nuclear factor kappaB-binding
      activity as well as lung myeloperoxidase activity and tumor necrosis factor alpha
      production. The data indicate that TLR4 plays a central role in TH-induced
      cardiac dysfunction. Toll-like receptor 4 deficiency or TLR4 inhibition
      attenuated cardiac dysfunction following TH, which may involve activation of the
      phosphoinositide 3-kinase/Akt signaling and decrease in nuclear factor kappaB
      binding activity. Toll-like receptor 4 antagonism may be a new and novel approach
      for the treatment and management of cardiac dysfunction in TH patients.

PMID- 24569515
TI  - Probing of 2 dimensional confinement-induced structural transitions in amorphous
      oxide thin film.
AB  - Whereas the atomic structure of surface of crystals is known to be distinct from
      that of bulk, experimental evidence for thickness-induced structural transitions
      in amorphous oxides is lacking. We report the NMR result for amorphous alumina
      with varying thickness from bulk up to 5 nm, revealing the nature of structural
      transitions near amorphous oxide surfaces/interfaces. The coordination
      environments in the confined amorphous alumina thin film are distinct from those
      of bulk, highlighted by a decrease in the fractions of high-energy clusters (and
      thus the degree of disorder) with thickness. The result implies that a wide range
      of variations in amorphous structures may be identified by controlling its
      dimensionality.

PMID- 24569516
TI  - Positive exchange-bias and giant vertical hysteretic shift in
      La0.3Sr0.7FeO3/SrRuO3 bilayers.
AB  - The exchange-bias effects in the mosaic epitaxial bilayers of the itinerant
      ferromagnet (FM) SrRuO3 and the antiferromagnetic (AFM) charge-ordered
      La(0.3)Sr(0.7)FeO3 were investigated. An uncharacteristic low-field positive
      exchange bias, a cooling-field driven reversal of positive to negative exchange
      bias and a layer thickness optimised unusual vertical magnetization shift were
      all novel facets of exchange bias realized for the first time in magnetic oxides.
      The successive magnetic training induces a transition from positive to negative
      exchange bias regime with changes in domain configurations. These observations
      are well corroborated by the hysteretic loop asymmetries which display the
      modifications in the AFM spin correlations. These exotic features emphasize the
      key role of i) mosaic disorder induced subtle interplay of competing AFM
      superexchange and FM double exchange at the exchange biased interface and, ii)
      training induced irrecoverable alterations in the AFM spin structure.

PMID- 24569509
TI  - Abandon the mouse research ship? Not just yet!
AB  - Many preclinical studies in critical care medicine and related disciplines rely
      on hypothesis-driven research in mice. The underlying premise posits that mice
      sufficiently emulate numerous pathophysiologic alterations produced by
      trauma/sepsis and can serve as an experimental platform for answering clinically
      relevant questions. Recently, the lay press severely criticized the translational
      relevance of mouse models in critical care medicine. A series of provocative
      editorials were elicited by a highly publicized research report in the
      Proceedings of the National Academy of Sciences (PNAS; February 2013), which
      identified an unrecognized gene expression profile mismatch between human and
      murine leukocytes following burn/trauma/endotoxemia. Based on their data, the
      authors concluded that mouse models of trauma/inflammation are unsuitable for
      studying corresponding human conditions. We believe this conclusion was not
      justified. In conjunction with resulting negative commentary in the popular
      press, it can seriously jeopardize future basic research in critical care
      medicine. We will address some limitations of that PNAS report to provide a
      framework for discussing its conclusions and attempt to present a balanced
      summary of strengths/weaknesses of use of mouse models. While many investigators
      agree that animal research is a central component for improved patient outcomes,
      it is important to acknowledge known limitations in clinical translation from
      mouse to man. The scientific community is responsible to discuss valid
      limitations without overinterpretation. Hopefully, a balanced view of the
      strengths/weaknesses of using animals for trauma/endotoxemia/critical care
      research will not result in hasty discount of the clear need for using animals to
      advance treatment of critically ill patients. 

PMID- 24569518
TI  - Inpatient nursing care and early warning scores: a workflow mismatch.
AB  - Early warning scores calculated by registered nurses (RNs) are used in hospitals
      to enhance the recognition of and communication about patient deterioration. This
      study evaluated workflow variables surrounding calculation and documentation of
      one pediatric hospital's use of an early warning score. Results indicated that
      there were significant delays in documentation of early warning scores by RNs and
      inconsistencies between the early warning scores and vital signs collected and
      documented by non-RN personnel. These findings reflected information obtained
      from the RNs about how they prioritize tasks and use work-arounds to specific
      systems issues regarding assessment and documentation in the electronic medical
      record. 

PMID- 24569517
TI  - Fluoxetine- and norfluoxetine-mediated complex drug-drug interactions: in vitro
      to in vivo correlation of effects on CYP2D6, CYP2C19, and CYP3A4.
AB  - Fluoxetine and its circulating metabolite norfluoxetine comprise a complex
      multiple-inhibitor system that causes reversible or time-dependent inhibition of
      the cytochrome P450 (CYP) family members CYP2D6, CYP3A4, and CYP2C19 in vitro.
      Although significant inhibition of all three enzymes in vivo was predicted, the
      areas under the concentration-time curve (AUCs) for midazolam and lovastatin were
      unaffected by 2-week dosing of fluoxetine, whereas the AUCs of dextromethorphan
      and omeprazole were increased by 27- and 7.1-fold, respectively. This observed
      discrepancy between in vitro risk assessment and in vivo drug-drug interaction
      (DDI) profile was rationalized by time-varying dynamic pharmacokinetic models
      that incorporated circulating concentrations of fluoxetine and norfluoxetine
      enantiomers, mutual inhibitor-inhibitor interactions, and CYP3A4 induction. The
      dynamic models predicted all DDIs with less than twofold error. This study
      demonstrates that complex DDIs that involve multiple mechanisms, pathways, and
      inhibitors with their metabolites can be predicted and rationalized via
      characterization of all the inhibitory species in vitro. 

PMID- 24569519
TI  - Functional characterization of exopolyphosphatase/guanosine pentaphosphate
      phosphohydrolase (PPX/GPPA) of Campylobacter jejuni.
AB  - The inorganic polyphosphate (poly-P) is a key regulator of stress responses and
      virulence in many bacterial pathogens including Campylobacter jejuni. The role of
      exopolyphosphatases/guanosine pentaphosphate (pppGpp) phosphohydrolases
      (PPX/GPPA) in poly-P homeostasis and C. jejuni pathobiology remains unexplored.
      Here, we analyzed deletion mutants (?ppx1, ?ppx2) and the double knockout mutant
      (dkppx), all ?ppx mutants exhibited increased capacity to accumulate poly-P;
      however only ?ppx1 and dkppx mutants showed decreased accumulation of ppGpp, an
      alarmone molecule that regulates stringent response in bacteria, suggesting
      potential dual role for PPX1/GPPA. Nutrient survival defect of ?ppx mutants was
      rescued by the supplementation of specific amino acids implying that survival
      defect may be associated with decreased ppGpp and/ or increased poly-P in ?ppx
      mutants. The ppk1 and spoT were upregulated in both ?ppx1 and ?ppx2 suggesting a
      compensatory role for SpoT and Ppk1 in poly-P and ppGpp homeostasis. The lack of
      ppx genes resulted in defects in motility, biofilm formation, nutrient stress
      survival, invasion and intracellular survival indicating that maintaining a
      certain level of poly-P is critical for ppx genes in C. jejuni pathophysiology.
      Both ppx1 and ppx2 mutants were resistant to human complement-mediated killing;
      however, the dkppx mutant was sensitive. The serum susceptibility did not occur
      in the presence of MgCl 2 and EGTA suggesting an involvement of the classical or
      lectin pathway of complement mediated killing. Interestingly, the chicken serum
      did not have any effect on the ?ppx mutants' survival. The observed serum
      susceptibility was not related to C. jejuni surface capsule and
      lipooligosaccharide structures. Our study underscores the importance of PPX/GPPA
      proteins in poly-P and ppGpp homeostasis, two critical molecules that modulate
      environmental stress responses and virulence in C. jejuni. 

PMID- 24569521
TI  - Biomimetic aerobic oxidative hydroxylation of arylboronic acids to phenols
      catalysed by a flavin derivative.
AB  - Flavin-catalysed oxidative hydroxylation of substituted arylboronic acids by
      molecular oxygen with the assistance of hydrazine or ascorbic acid resulted in
      phenols in high yields. This mild organocatalytic protocol is compatible with a
      variety of functional groups and it is alternatively usable for transformation of
      alkylboronic acids to alcohols. Reaction takes place also in water and fulfils
      criteria for a green procedure.

PMID- 24569524
TI  - Chest pain and neck discomfort in a young man.

PMID- 24569528
TI  - Simulation of the shape and size of casein micelles in a film state.
AB  - Size fractionated casein micelles (CMs) form homogeneous films in which they are
      densely packed. The lateral size of CMs in films can be well resolved by surface
      sensitive methods, but the estimation of their heights is still a challenge. We
      show that height information can be obtained from scattering patterns of GISAXS
      experiments on highly ordered casein films. We use an elastic scattering approach
      within the distorted wave Born approximation (DWBA) to simulate for the first
      time the two-dimensional intensity distribution of a GISAXS experiment of the CM
      near their critical angle. The model which fits the GISAXS data best considers an
      ellipsoidal form factor for the CM and an arrangement on a hexagonal lattice. Our
      results indicate that during film formation the spherical solution structure of
      CMs becomes compressed in the direction perpendicular to the film surface. In the
      film state, the micelles assume an oblate ellipsoidal shape with an aspect ratio
      of 1.9. Hence, their surface and contact area to the surrounding increases. As a
      result, the density of kappa-casein on the micellar surface decreases, which
      could influence the functional properties of coatings and films.

PMID- 24569525
TI  - Error in the honeybee waggle dance improves foraging flexibility.
AB  - The honeybee waggle dance communicates the location of profitable food sources,
      usually with a certain degree of error in the directional information ranging
      from 10-15 degrees  at the lower margin. We simulated one-day colonial foraging
      to address the biological significance of information error in the waggle dance.
      When the error was 30 degrees  or larger, the waggle dance was not beneficial. If
      the error was 15 degrees , the waggle dance was beneficial when the food sources
      were scarce. When the error was 10 degrees  or smaller, the waggle dance was
      beneficial under all the conditions tested. Our simulation also showed that
      precise information (0-5 degrees  error) yielded great success in finding
      feeders, but also caused failures at finding new feeders, i.e., a high-risk high
      return strategy. The observation that actual bees perform the waggle dance with
      an error of 10-15 degrees  might reflect, at least in part, the maintenance of a
      successful yet risky foraging trade-off. 

PMID- 24569522
TI  - Early-life viral infections and the development of asthma: a target for asthma
      prevention?
AB  - PURPOSE OF REVIEW: To discuss the recent insights into the relationships between
      viral respiratory infections and asthma inception in the context of a long-term
      goal of moving toward prevention strategies for childhood asthma. RECENT
      FINDINGS: There is strong evidence for respiratory syncytial virus and human
      rhinovirus wheezing illnesses as important risk factors for asthma inception. The
      mechanisms underlying these relationships have been an intense area of study.
      Novel approaches for the prevention of virus infections and/or lessening the
      severity of associated illnesses are at various stages of development, and are
      important potential tools in efforts aimed at primary and secondary prevention of
      asthma. SUMMARY: Viral respiratory infections in early life are a major source of
      morbidity and are critical in the development of asthma. Mechanisms by which
      these infections lead to asthma inception in susceptible individuals are
      emerging. Further, there are promising potential interventions currently
      available that should be tested in clinical trials. The goal of prevention of
      disease inception is clearly on the horizon.

PMID- 24569530
TI  - Enzyme-promoted regioselective coupling oligomerization of isorhapontigenin
      towards the first synthesis of (+/-)-gnetulin.
AB  - We report the first synthesis of a natural (+/-)-gnetulin and an unnatural
      analogue of (+/-)-gnemonol M by using the regioselective oxidative coupling
      reactions of 5-tert-butyl-isorhapontigenin as the key step. Both the effects of
      different enzyme-catalyzed systems on the structures of coupling products and
      structural transformations of coupling products in the presence of several Lewis
      acids were systematically investigated. 

PMID- 24569520
TI  - Dynamic survey of mitochondria by ubiquitin.
AB  - Ubiquitin is a post-translational modifier with proteolytic and non-proteolytic
      roles in many biological processes. At mitochondria, it performs regulatory
      homeostatic functions and contributes to mitochondrial quality control. Ubiquitin
      is essential for mitochondrial fusion, regulates mitochondria-ER contacts, and
      participates in maternal mtDNA inheritance. Under stress, mitochondrial
      dysfunction induces ubiquitin-dependent responses that involve mitochondrial
      proteome remodeling and culminate in organelle removal by mitophagy. In addition,
      many ubiquitin-dependent mechanisms have been shown to regulate innate immune
      responses and xenophagy. Here, we review the emerging roles of ubiquitin at
      mitochondria. 

PMID- 24569531
TI  - Extended scale for the hydrogen-bond basicity of ionic liquids.
AB  - In the past decade, ionic liquids (ILs) have been the focus of intensive research
      regarding their use as potential and alternative solvents in many chemical
      applications. Targeting their effectiveness, recent investigations have attempted
      to establish polarity scales capable of ranking ILs according to their chemical
      behaviours. However, some major drawbacks have been found since polarity scales
      only report relative ranks because they depend on the set of probe dyes used, and
      they are sensitive to measurement conditions, such as purity levels of the ILs
      and procedures employed. Due to all these difficulties it is of crucial
      importance to find alternative and/or predictive methods and to evaluate them as
      a priori approaches capable of providing the chemical properties of ILs.
      Furthermore, the large number of ILs available makes their experimental
      characterization, usually achieved by a trial and error methodology, burdensome.
      In this context, we firstly evaluated COSMO-RS, COnductor-like Screening MOdel
      for Real Solvents, as an alternative tool to estimate the hydrogen-bond basicity
      of ILs. After demonstrating a straight-line correlation between the experimental
      hydrogen-bond basicity values and the COSMO-RS hydrogen-bonding energies in
      equimolar cation-anion pairs, an extended scale for the hydrogen-bond accepting
      ability of IL anions is proposed here. This new ranking of the ILs' chemical
      properties opens the possibility to pre-screen appropriate ILs (even those not
      yet synthesized) for a given task or application. 

PMID- 24569529
TI  - SILAC-based proteomic quantification of chemoattractant-induced cytoskeleton
      dynamics on a second to minute timescale.
AB  - Cytoskeletal dynamics during cell behaviours ranging from endocytosis and
      exocytosis to cell division and movement is controlled by a complex network of
      signalling pathways, the full details of which are as yet unresolved. Here we
      show that SILAC-based proteomic methods can be used to characterize the rapid
      chemoattractant-induced dynamic changes in the actin-myosin cytoskeleton and
      regulatory elements on a proteome-wide scale with a second to minute timescale
      resolution. This approach provides novel insights in the ensemble kinetics of key
      cytoskeletal constituents and association of known and novel identified binding
      proteins. We validate the proteomic data by detailed microscopy-based analysis of
      in vivo translocation dynamics for key signalling factors. This rapid large-scale
      proteomic approach may be applied to other situations where highly dynamic
      changes in complex cellular compartments are expected to play a key role. 

PMID- 24569532
TI  - Prospective echocardiographic assessment of cardiac structure and function in
      Chinese persons living with HIV.
AB  - BACKGROUND: Persons living with human immunodeficiency virus (HIV) are at
      increased risk of developing cardiovascular disease. Few studies have focused on
      echocardiographic abnormalities in this population. METHODS: China AIDS Clinical
      Trial 0810 is a prospective, multicenter cohort study of persons living with HIV
      (PLWH). We performed an echocardiography substudy of 325 PLWH. We examined the
      prevalence of left ventricular systolic dysfunction (LVSD), diastolic dysfunction
      (DD), pulmonary arterial hypertension (PAH), and increased left ventricular mass
      (ILVM) in antiretroviral therapy (ART)-naive PLWH at baseline and week 48 after
      initiation of ART. RESULTS: Compared with age- and sex-matched healthy controls,
      PLWH had a higher prevalence of DD (16.5% vs 7.2%, P < .027) and a marginally
      significant higher prevalence of LVSD (7.3% vs 2.1%, P = .056). The increase in
      the prevalence of DD from baseline to week 48 in PLWH was marginally significant
      (P = .056). No significant difference was observed in the prevalence of LVSD,
      PAH, or ILVM at baseline and week 48 in PLWH. In logistic regression analysis of
      all participants, age was significantly associated with LVSD; HIV infection, age,
      and hypertension were associated with DD whereas HIV infection and hypertension
      were associated with ILVM at baseline. Logistic regression analysis of PLWH
      showed that only age was significantly associated with LVSD and DD. CONCLUSIONS:
      The prevalence of echocardiographic abnormalities was significantly higher in ART
      naive PLWH than in controls. HIV infection was significantly associated with
      cardiac abnormalities. No significant change in echocardiographic abnormalities
      was observed after 48 weeks of ART. Longer-term prospective studies are
      warranted.

PMID- 24569534
TI  - Examination of the psychometric properties of the Personal Growth Initiative
      Scale-II in African American college students.
AB  - Personal growth initiative (PGI), an individual's active and intentional desire
      to engage in the growth process, has been an important construct in studies of
      physical and mental health around the world. However, there is a dearth of
      research examining this construct in African American samples. In addition, PGI
      has recently undergone a revision of both its theory and measure; the resulting
      Personal Growth Initiative Scale-II (PGIS-II) has been validated for use only
      with European American and international college student samples. The current
      study examined the psychometric properties of the PGIS-II in a sample of African
      American college students. Confirmatory factor analyses yielded results
      consistent with previous studies, and the PGIS-II showed evidence of convergent
      and discriminant validity for three of its four factors. In addition, the PGIS-II
      was significantly related to aspects of Black racial identity, suggesting that it
      is a viable construct in this population. 

PMID- 24569535
TI  - Coffee ground vomitus in 84-year-old male.

PMID- 24569533
TI  - Relationship between alcohol use categories and noninvasive markers of advanced
      hepatic fibrosis in HIV-infected, chronic hepatitis C virus-infected, and
      uninfected patients.
AB  - BACKGROUND: It is unclear if the risk of liver disease associated with different
      levels of alcohol consumption is higher for patients infected with human
      immunodeficiency virus (HIV) or chronic hepatitis C virus (HCV). We evaluated
      associations between alcohol use categories and advanced hepatic fibrosis, by HIV
      and chronic HCV status. METHODS: We performed a cross-sectional study among
      participants in the Veterans Aging Cohort Study who reported alcohol consumption
      at enrollment (701 HIV/HCV-coinfected; 1410 HIV-monoinfected; 296 HCV
      monoinfected; 1158 HIV/HCV-uninfected). Alcohol use category was determined by
      the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) questionnaire
      and alcohol-related diagnoses and was classified as nonhazardous drinking,
      hazardous/binge drinking, or alcohol-related diagnosis. Advanced hepatic fibrosis
      was defined by FIB-4 index >3.25. RESULTS: Within each HIV/HCV group, the
      prevalence of advanced hepatic fibrosis increased as alcohol use category
      increased. For each alcohol use category, advanced hepatic fibrosis was more
      common among HIV-infected than uninfected (nonhazardous: 6.7% vs 1.4%;
      hazardous/binge: 9.5% vs 3.0%; alcohol-related diagnosis: 19.0% vs 8.6%; P < .01)
      and chronic HCV-infected than uninfected (nonhazardous: 13.6% vs 2.5%;
      hazardous/binge: 18.2% vs 3.1%; alcohol-related diagnosis: 22.1% vs 6.5%; P <
      .01) participants. Strong associations with advanced hepatic fibrosis (adjusted
      odds ratio [95% confidence interval]) were observed among HIV/HCV-coinfected
      patients with nonhazardous drinking (14.2 [5.91-34.0]), hazardous/binge drinking
      (18.9 [7.98-44.8]), and alcohol-related diagnoses (25.2 [10.6-59.7]) compared
      with uninfected nonhazardous drinkers. CONCLUSIONS: Advanced hepatic fibrosis was
      present at low levels of alcohol consumption, increased with higher alcohol use
      categories, and was more prevalent among HIV-infected and chronic HCV-infected
      patients than uninfected individuals. All alcohol use categories were strongly
      associated with advanced hepatic fibrosis in HIV/HCV-coinfected patients.

PMID- 24569537
TI  - Severe and prolonged hypophosphatemia after intravenous iron administration in a
      malnourished patient.
AB  - Malnutrition may result in a phosphate-deficient state owing to a chronically
      insufficient phosphate intake. Concomitant iron deficiency is common and often
      supplemented by the intravenous route. It is not widely recognized that some
      parenteral iron formulations can induce hypophosphatemia. Herein we report a case
      of a severe and symptomatic hypophosphatemia (0.18 mM, normal range 0.8-1.4 mM)
      associated with an inappropriately reduced tubular reabsorption of phosphate
      (33%, norm >95%) in a malnourished patient with anorexia/bulimia who received 2 *
      500 mg iron carboxymaltose (FCM) intravenously. Despite intravenous and oral
      phosphate supplements, it required 2 months to achieve a normal serum phosphate
      level. Our case demonstrates that in a chronically malnourished and phosphate
      deficient state intravenous FCM could potentially be dangerous. If this form of
      iron application cannot be avoided, phosphate supplementation before and after
      iron infusion as well as close monitoring of phosphate levels are needed.

PMID- 24569536
TI  - The effects of probiotic bacteria on glycaemic control in overweight men and
      women: a randomised controlled trial.
AB  - BACKGROUND/OBJECTIVES: Evidence from animal and in vitro models suggest a role of
      probiotic bacteria in improving glycaemic control and delaying the onset of type
      2 diabetes. However, the evidence from controlled trials in humans is limited.
      The objective was to determine if the probiotic bacteria L. acidophilus La5 and
      B. animalis subsp lactis Bb12, supplemented in a whole food (yoghurt) or isolated
      (capsules) form, can improve biomarkers of glycaemic control. SUBJECTS/METHODS:
      Following a 3-week washout period, 156 overweight men and women over 55 years
      (mean age: 67 +/- 8 years; mean body mass index (31 +/- 4 kg/m(2)) were
      randomized to a 6-week double-blinded parallel study. The four intervention
      groups were: (A) probiotic yoghurt plus probiotic capsules; (B) probiotic yoghurt
      plus placebo capsules; (C) control milk plus probiotic capsules; and (D) control
      milk plus placebo capsules. Outcome measurements, including fasting glucose,
      insulin, glycated haemoglobin and Homoeostasis Model Assessment of Insulin
      Resistance (HOMA-IR), were performed at baseline and week 6. RESULTS: Relative to
      the milk-control group, probiotic yoghurt resulted in a significantly higher HOMA
      IR (0.32 +/- 0.15, P=0.038), but did not have a significant effect on the other
      three measures of glycaemic control (P>0.05). Relative to placebo capsules,
      probiotic capsules resulted in a significantly higher fasting glucose (0.15 +/-
      0.07 mmol/l, P=0.037), with no significant effect on the other three measures of
      glycaemic control (P>0.05). Further analyses did not identify other variables as
      contributing to these adverse findings. CONCLUSIONS: Data from this study does
      not support the hypothesis that L. acidophilus La5 and B. animalis subsp lactis
      Bb12, either in isolated form or as part of a whole food, benefit short-term
      glycaemic control. Indeed, there is weak data for an adverse effect of these
      strains on glucose homoeostasis.

PMID- 24569538
TI  - Efficacy and safety of the probiotic Lactobacillus paracasei LP-33 in allergic
      rhinitis: a double-blind, randomized, placebo-controlled trial (GA2LEN Study).
AB  - BACKGROUND/OBJECTIVES: An imbalance between Th1 and Th2 cells is involved in
      allergic rhinitis (AR) that may be improved by probiotics. To test the efficacy
      of the probiotic Lactobacillus paracasei subsp. paracasei LP-33, a double-blind,
      placebo-controlled, randomized trial was carried out in patients with AR to grass
      pollen treated with loratadine and presenting altered quality of life.
      SUBJECTS/METHODS: Subjects with persistent AR, symptomatic during the grass
      pollen season, and a positive skin test or specific immunoglobulin E to grass
      pollens were included by general practitioners (GPs). All received loratadine for
      5 weeks. The primary end point was the improvement in Rhinitis Quality of Life
      (RQLQ) global score at the fifth week of LP-33 consumption compared with placebo
      (in addition to loratadine). Secondary end points included nasal and ocular
      symptoms (individual and total symptom scores), visual analogue scale and time of
      first exacerbation of the symptoms when loratadine was stopped. RESULTS: A total
      of 425 subjects were included. Using intent-to-treat analysis, the RQLQ global
      score decreased significantly more in the LP-33 group than in the placebo group
      (P=0.0255, difference=-0.286 (95% confidence interval (CI): -0.536; -0.035)). No
      significant differences were noted for the change of the rhinitis total symptom
      score 5 global score between groups (P=0.1288, difference=-0.452 (95% CI: -1.036;
      0.132)). Significant differences in ocular symptoms (RQLQ) were observed between
      groups (P=0.0029, difference=-0.4087 (95% CI: -0.6768; -0.1407)). CONCLUSIONS:
      This study performed by GPs shows that LP-33 improves the quality of life of
      subjects with persistent AR who are currently being treated with an oral H1
      antihistamine. Whereas nasal symptoms had not changed, ocular symptoms had
      consistently improved.

PMID- 24569539
TI  - Association between erythrocyte membrane fatty acids and biomarkers of
      dyslipidemia in the EPIC-Potsdam study.
AB  - BACKGROUND/OBJECTIVE: Blood proportions of fatty acids (FAs) and FA-ratios
      reflecting desaturase activity are associated with the risk of chronic diseases
      like type 2 diabetes mellitus or cardiovascular diseases. Biomarkers of
      dyslipidemia are considered as potential mediators of this association. We
      evaluated associations of erythrocyte membrane proportions of individual disease
      related polyunsaturated fatty acids (PUFAs), trans-FAs, dairy-derived saturated
      FAs (SFAs) (15:0, 17:0) and FA-ratios with biomarkers of dyslipidemia (high
      density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol,
      non-HDL-cholesterol, triglycerides). SUBJECTS/METHODS: We conducted a cross
      sectional analysis of a subsample (n=1759) of the European Prospective
      Investigation into Cancer and Nutrition (EPIC)-Potsdam study. Associations of
      individual FAs and FA-ratios with plasma biomarkers of dyslipidemia were
      evaluated by linear multivariable regression. RESULTS: Most notably, FA-ratios
      reflecting activity of Delta6-desaturase (D6D) and stearoyl-coenzyme A-desaturase
      (SCD) were positively associated with triglyceride and LDL-cholesterol
      concentrations (adjusted means (95% confidence interval (CI)) of triglycerides
      (mg/dl) across D6D tertiles: men--102 (94.7-110), 111 (104-120), 144 (134-156)
      and women--73.5 (70.0-77.2), 82.9 (79.0-86.9), 94.2 (89.7-98.9)); across SCD
      tertiles: men--99.0 (91.8-107), 115 (107-124), 144 (134-156) and women--72.4
      (69.0-76.0), 81.5 (77.8-85.5), 97.2 (92.6-102)), whereas inverse associations
      with triglycerides were observed for the estimated Delta5-desaturase (D5D)
      activity (adjusted means (95% CI) of triglycerides (mg/dl) across D5D tertiles:
      men--128 (119-138), 121 (113-131), 106 (97.9-114) and women--92.0 (87.6-96.6),
      82.8 (78.9-86.9), 75.3 (71.6-79.1), P-values for trend at least 0.0006).
      Furthermore, we observed generally weaker and less consistent associations of
      dairy-derived SFAs (mainly 17:0) with triglycerides and HDL-cholesterol.
      Individual PUFAs and trans-FAs were, if at all, only weakly associated with
      dyslipidemia markers. CONCLUSIONS: Our findings suggest that triglyceride and LDL
      cholesterol concentrations may be mediators that link intake and metabolism of
      FAs to metabolic risk.

PMID- 24569540
TI  - Sarcopenia assessment project in the nursing homes in Turkey.
AB  - BACKGROUND/OBJECTIVES: Sarcopenia and sarcopenic obesity (SO) are geriatric
      syndromes leading to physical disability, poor quality of life and death. The aim
      of this study was to investigate the prevalence of sarcopenia and SO in nursing
      homes in Turkey and to define local disparities for diagnosing sarcopenia and SO.
      SUBJECTS/METHODS: This cross-sectional multicenter study was performed in 711
      patients in 14 nursing homes. Comprehensive geriatric assessment tests, handgrip
      strength and calf circumference (CC) measurements were carried out. Sarcopenia
      was both defined by handgrip strength and CC criteria. RESULTS: According to
      handgrip strength measurement, 483 (68%) of patients were sarcopenic (male: 72%,
      female: 63.8%), 228 were non-sarcopenic. The prevalence of SO was 22% (13.7% in
      men, 30.2% in women). Patients (82.5%) who were diagnosed as sarcopenic by the
      handgrip strength test were not sarcopenic according to CC sarcopenia criteria.
      Therefore, we tried to determine the optimal CC value for diagnosing sarcopenia
      in our population. CONCLUSIONS: Both sarcopenia and SO were prevalent among
      Turkish nursing home elderly residents. Most of the patients with sarcopenia were
      obese or overweight. We showed that diagnosing sarcopenia with CC measurement
      underestimated the sarcopenia prevalence assessed by handgrip strength. So we
      concluded that, although different assessment methods are recommended for the
      diagnosis of sarcopenia local disparities should be considered.

PMID- 24569541
TI  - Are field measures of adiposity sufficient to establish fatness-related linkages
      with metabolic outcomes in adolescents?
AB  - OBJECTIVE: To examine the associations between the adiposity-related information
      conveyed by field fatness measures: body mass index (BMI), waist circumference
      (WC) and sum of triceps and subscapular skinfolds (SUM SF) relative to dual
      energy X-ray absorptiometry (DXA), beyond their common intercorrelations, with
      three important metabolic variables in US adolescents. METHODS: We analyzed data
      on adiposity and insulin resistance (HOMA-IR), serum triglycerides (TGs) and
      total cholesterol (TC) from three US national surveys. In two-stage least-square
      modeling, we first calculated the common adiposity variance, and then used
      multivariate linear and quantile regressions to access residual associations with
      each measure. RESULTS: Basic associations for each of the adiposity measures were
      similar but differences emerged in residual adiposity analyses scaled by s.d.
      units. While a 1 s.d. change in residual variance in DXA total fat beyond that
      accounted for by BMI (DXA|BMI) was strongly and significantly associated with all
      outcomes, associations with DXA accounting for SUM SF (DXA|SUM SF) and WC
      (DXA|WC) were weak or nonsignificant. Contrasted amongst themselves, the residual
      score association between BMI|SUM SF (beta=0.06, P<0.0001) and HOMA-IR was
      weaker, and half as strong as that for the converse, SUM SF|BMI (beta=0.13,
      P=0.020). SUM SF|WC was stronger than WC|SUM SF (beta=0.08, P<0.0001 vs SUM SF|WC
      beta=0.13, P<0.0001). Associations were similar for TGs and TC. CONCLUSIONS:
      Laboratory methods like DXA offer minimal explanatory advantage over field
      methods in assessing adiposity-related contributions to metabolic outcomes in
      adolescents. Among the simple fatness measures, skinfolds convey additional
      information beyond BMI and WC when estimating associations both at the population
      mean and at the upper extremes of metabolic factors.

PMID- 24569542
TI  - Effect of fructose on markers of non-alcoholic fatty liver disease (NAFLD): a
      systematic review and meta-analysis of controlled feeding trials.
AB  - BACKGROUND/OBJECTIVES: In the absence of consistent clinical evidence, there are
      concerns that fructose contributes to non-alcoholic fatty liver disease (NAFLD).
      To determine the effect of fructose on markers of NAFLD, we conducted a
      systematic review and meta-analysis of controlled feeding trials.
      SUBJECTS/METHODS: We searched MEDLINE, EMBASE, CINAHL and the Cochrane Library
      (through 3 September 2013). We included relevant trials that involved a follow-up
      of >= 7 days. Two reviewers independently extracted relevant data. Data were
      pooled by the generic inverse variance method using random effects models and
      expressed as standardized mean difference (SMD) for intrahepatocellular lipids
      (IHCL) and mean difference (MD) for alanine aminotransferase (ALT). Inter-study
      heterogeneity was assessed (Cochran Q statistic) and quantified (I(2) statistic).
      RESULTS: Eligibility criteria were met by eight reports containing 13 trials in
      260 healthy participants: seven isocaloric trials, in which fructose was
      exchanged isocalorically for other carbohydrates, and six hypercaloric trials, in
      which the diet was supplemented with excess energy (+21-35% energy) from high
      dose fructose (+104-220 g/day). Although there was no effect of fructose in
      isocaloric trials, fructose in hypercaloric trials increased both IHCL (SMD=0.45
      (95% confidence interval (CI): 0.18, 0.72)) and ALT (MD=4.94 U/l (95% CI: 0.03,
      9.85)). LIMITATIONS: Few trials were available for inclusion, most of which were
      small, short (<= 4 weeks), and of poor quality. CONCLUSIONS: Isocaloric exchange
      of fructose for other carbohydrates does not induce NAFLD changes in healthy
      participants. Fructose providing excess energy at extreme doses, however, does
      raise IHCL and ALT, an effect that may be more attributable to excess energy than
      fructose. Larger, longer and higher-quality trials of the effect of fructose on
      histopathological NAFLD changes are required.

PMID- 24569543
TI  - Obesity prevalence in relation to gut microbial environments capable of producing
      equol or O-desmethylangolensin from the isoflavone daidzein.
AB  - BACKGROUND/OBJECTIVES: Studies have observed associations between the gut
      microbiome and obesity. O-desmethylangolensin (ODMA) and equol are gut bacterial
      metabolites of daidzein, a compound found in high amounts in soy foods.
      Approximately 80-95% and 25-60% of individuals harbor gut microbial communities
      capable of producing ODMA or equol, respectively. Given that other phenotypes of
      gut bacterial metabolism of dietary compounds have been associated with obesity,
      we hypothesized that daidzein-metabolizing phenotypes would be associated with
      obesity. The objective of this study was to compare the prevalence of ODMA
      producer and equol-producer phenotypes in obese, overweight and normal-weight
      individuals. SUBJECTS/METHODS: Adults aged 18-95 years (n=297) provided a first
      void urine sample after a 3-day soy challenge, and urinary ODMA and equol
      concentrations were used to classify individuals as producers or non-producers.
      Body mass index was calculated from self-reported weight and height. RESULTS:
      There were 60 ODMA non-producers and 173 equol non-producers. Obese individuals
      were 2.8 times more likely to be ODMA non-producers (odds ratio (OR)=2.8, 95%
      confidence interval (CI): 1.2, 6.2) compared with normal-weight individuals, when
      adjusted for age, race (white vs non-white), and gender and menopausal status
      (male, premenopausal female and postmenopausal female). Obesity was not
      associated with equol-producer phenotype (OR=1.1, 95% CI: 0.5, 2.2). Stronger
      associations with obesity were observed in the ODMA non-producers who were also
      equol producers than in the equol non-producers. CONCLUSIONS: Results from this
      analysis suggest that the ODMA-producer phenotype, but not equol-producer
      phenotype, is associated with obesity in adults. These results support further
      work to replicate these findings and evaluate the mechanisms of the observed
      associations.

PMID- 24569546
TI  - Lost in translation.

PMID- 24569544
TI  - A functional Kv1.2-hERG chimaeric channel expressed in Pichia pastoris.
AB  - Members of the six-transmembrane segment family of ion channels share a common
      structural design. However, there are sequence differences between the members
      that confer distinct biophysical properties on individual channels. Currently, we
      do not have 3D structures for all members of the family to help explain the
      molecular basis for the differences in their biophysical properties and
      pharmacology. This is due to low-level expression of many members in native or
      heterologous systems. One exception is rat Kv1.2 which has been overexpressed in
      Pichia pastoris and crystallised. Here, we tested chimaeras of rat Kv1.2 with the
      hERG channel for function in Xenopus oocytes and for overexpression in Pichia.
      Chimaera containing the S1-S6 transmembrane region of HERG showed functional and
      pharmacological properties similar to hERG and could be overexpressed and
      purified from Pichia. Our results demonstrate that rat Kv1.2 could serve as a
      surrogate to express difficult-to-overexpress members of the six-transmembrane
      segment channel family. 

PMID- 24569547
TI  - Stagnation point flow and mass transfer with chemical reaction past a
      stretching/shrinking cylinder.
AB  - This paper is about the stagnation point flow and mass transfer with chemical
      reaction past a stretching/shrinking cylinder. The governing partial differential
      equations in cylindrical form are transformed into ordinary differential
      equations by a similarity transformation. The transformed equations are solved
      numerically using a shooting method. Results for the skin friction coefficient,
      Schmidt number, velocity profiles as well as concentration profiles are presented
      for different values of the governing parameters. Effects of the curvature
      parameter, stretching/shrinking parameter and Schmidt number on the flow and mass
      transfer characteristics are examined. The study indicates that dual solutions
      exist for the shrinking cylinder but for the stretching cylinder, the solution is
      unique. It is observed that the surface shear stress and the mass transfer rate
      at the surface increase as the curvature parameter increases. 

PMID- 24569545
TI  - The deadly connection between endoplasmic reticulum, Ca2+, protein synthesis, and
      the endoplasmic reticulum stress response in malignant glioma cells.
AB  - BACKGROUND: The endoplasmic reticulum (ER) is involved in Ca(2+) signaling and
      protein processing. Accumulation of unfolded proteins following ER Ca(2+)
      depletion triggers the ER stress response (ERSR), which facilitates protein
      folding and removal of damaged proteins and can induce cell death. Unfolded
      proteins bind to chaperones, such as the glucose-regulated protein (GRP)78 and
      cause the release of GRP78-repressed proteins executing ERSR. METHODS: Several
      glioma cell lines and primary astrocytes were used to analyze ERSR using standard
      western blots, reverse transcription-PCR, viability assays, and single cell
      Ca(2+) imaging. RESULTS: ERSR induction with thapsigargin results in a more
      intense ERSR associated with a larger loss of ER Ca(2+), activation of ER
      associated caspases (4/12) and caspase 3, and a higher rate of malignant glioma
      cell death than in normal glial cells. Malignant glioma cells have higher levels
      of protein synthesis and expression of the translocon (a component of the
      ribosomal complex, guiding protein entry in the ER), the activity of which is
      associated with the loss of ER Ca(2+). Our experiments confirm increased
      expression of the translocon in malignant glioma cells. In addition, blockade of
      the ribosome-translocon complex with agents differently affecting translocon
      Ca(2+) permeability causes opposite effects on ERSR deployment and death of
      malignant glioma cells. CONCLUSIONS: Excessive ER Ca(2+) loss due to translocon
      activity appears to be responsible for the enhancement of ERSR, leading to the
      death of glioma cells. The results reveal a characteristic of malignant glioma
      cells that could be exploited to develop new therapeutic strategies to treat
      incurable glial malignancies.

PMID- 24569548
TI  - Pancreas development in humans.
AB  - PURPOSE OF REVIEW: We highlight some of the major recent advances in
      characterizing human pancreas development and endocrine cell differentiation.
      RECENT FINDINGS: Extensive research efforts have helped to define crucial events
      in the mouse pancreas organogenesis. Information gained from these studies was
      used to develop human embryonic stem cell (hESC) differentiation protocols with
      the goal of generating functional glucose-responsive, insulin-producing human
      beta-cells. In spite of remarkable progress in hESC differentiation, current
      protocols based on mouse developmental biology can produce human beta-cells only
      in vivo. New differentiation markers and recently generated reagents may provide
      an unprecedented opportunity to develop a high-density expression map of human
      fetal pancreas and pancreatic islets that could serve as a reference point for in
      vitro hESC differentiation. SUMMARY: Integrating an increased knowledge of human
      pancreas development into hESC differentiation protocols has the potential to
      greatly advance our ability to generate functional insulin-producing cells for
      beta-cell replacement therapy.

PMID- 24569549
TI  - The nonhuman primate as a model for type 2 diabetes.
AB  - PURPOSE OF THE REVIEW: Although rodent models provide insight into the mechanisms
      underlying type 2 diabetes mellitus (T2DM), they are limited in their
      translatability to humans. The nonhuman primate (NHP) shares important metabolic
      similarities with the human, making it an ideal model for the investigation of
      type 2 diabetes and use in preclinical trials. This review highlights the key
      contributions in the field over the last year using the NHP model. RECENT
      FINDINGS: The NHP has not only provided novel insight into the normal and
      pathological processes that occur within the islet, but has also allowed for the
      preclinical testing of novel pharmaceutical targets for obesity and T2DM.
      Particularly, administration of fibroblast growth factor-21 in the NHP resulted
      in weight loss and improvements in metabolic health, supporting rodent studies
      and recent clinical trials. In addition, the NHP was used to demonstrate that a
      novel melanocortin-4 receptor agonist did not cause adverse cardiovascular
      effects. Finally, this model has been used to provide evidence that glucagon-like
      peptide-1-based therapies do not induce pancreatitis in the healthy NHP. SUMMARY:
      The insight gained from studies using the NHP model has allowed for a better
      understanding of the processes driving T2DM and has promoted the development of
      well tolerated and effective treatments.

PMID- 24569550
TI  - Bringing closed-loop home: recent advances in closed-loop insulin delivery.
AB  - PURPOSE OF REVIEW: To highlight the recent advances in closed-loop research, the
      development and progress towards utilizing closed loop outside of the clinical
      research setting and at patients' homes. RECENT FINDINGS: In spite of the modern
      insulin therapy in type 1 diabetes, hypoglycaemia is still a major limiting
      factor. This often leads to suboptimal glycaemic control and risk of diabetes
      complications. Closed loop has been shown to improve glycaemic control whilst
      avoiding hypoglycaemia. Incremental progress has been made in this field, from
      the use of automated systems and bihormonal closed-loop systems in clinical
      research facility settings under close supervision to the use of ambulatory
      closed-loop prototype at patients' homes in free-living conditions. Different
      population of patients with type 1 diabetes and control algorithm approaches have
      been studied, assessing the efficacy and safety. Transitional and home studies
      present different challenges at achieving better glycaemic outcome with closed
      loop. Improved glucose sensor reliability may accelerate the clinical use and
      faster insulin analogues increase the clinical utility. SUMMARY: Results and
      experience with closed-loop insulin delivery have been encouraging, leading the
      way for future improvements and development in the field, to make closed loop
      suitable for use in clinical practice.

PMID- 24569553
TI  - Scavenger receptor class B type I and immune dysfunctions.
AB  - PURPOSE OF REVIEW: To summarize the recent findings about the roles of scavenger
      receptor class B type I (SR-BI) in immunity and discuss the underlying mechanisms
      by which SR-BI prevents immune dysfunctions. RECENT FINDINGS: SR-BI is well known
      as a high-density lipoprotein (HDL) receptor playing key roles in HDL metabolism
      and in protection against atherosclerosis. Recent studies have indicated that SR
      BI is also an essential modulator in immunity. SR-BI deficiency in mice causes
      immune dysfunctions, including increased atherosclerosis, elevated susceptibility
      to sepsis, impaired lymphocyte homeostasis, and autoimmune disorders. SR-BI
      exerts its protective roles through a variety of HDL-dependent and HDL
      independent mechanisms. SR-BI is also involved in hepatitis C virus cell entry. A
      deficiency of SR-BI in humanized mice has been shown to decrease hepatitis C
      virus infectivity. SUMMARY: SR-BI regulates immunity via multiple mechanisms and
      its deficiency causes numerous diseases. A comprehensive understanding of the
      roles of SR-BI in protection against immune dysfunctions may provide a
      therapeutic target for intervention against its associated diseases.

PMID- 24569551
TI  - Human beta-cell regeneration: progress, hurdles, and controversy.
AB  - PURPOSE OF REVIEW: Therapies that increase functional beta-cell mass may be the
      best long-term treatment for diabetes. Significant resources are devoted toward
      this goal, and progress is occurring at a rapid pace. Here, we summarize recent
      advances relevant to human beta-cell regeneration. RECENT FINDINGS: New beta
      cells arise from proliferation of pre-existing beta-cells or transdifferentiation
      from other cell types. In addition, dedifferentiated beta-cells may populate
      islets in diabetes, possibly representing a pool of cells that could
      redifferentiate into functional beta-cells. Advances in finding strategies to
      drive beta-cell proliferation include new insight into proproliferative factors,
      both circulating and local, and elements intrinsic to the beta-cell, such as cell
      cycle machinery and regulation of gene expression through epigenetic modification
      and noncoding RNAs. Controversy continues in the arena of generation of beta
      cells by transdifferentiation from exocrine, ductal, and alpha cells, with
      studies producing both supporting and opposing data. Progress has been made in
      redifferentiation of beta-cells that have lost expression of beta-cell markers.
      SUMMARY: Although significant progress has been made, and promising avenues
      exist, more work is needed to achieve the goal of beta-cell regeneration as a
      treatment for diabetes.

PMID- 24569555
TI  - Do statins increase the risk of diabetes or is it guilt by association?
AB  - PURPOSE OF REVIEW: The aim of this review is to critically examine the relevant
      literature and ascertain whether the current evidence supports the validity of
      claims that statins increase the risk of diabetes. RECENT FINDINGS: In the past
      several years, a large number of studies and several meta-analyses based on these
      reports have suggested a significantly increased risk of type 2 diabetes
      associated with statin use, ranging from 6 to 48%. SUMMARY: Close examination and
      deconstruction of these reports reveal numerous flaws in the designs of the
      studies, insufficient or missing data, and misdirected or spinned assumptions
      that render the conclusions as highly inaccurate and misleading. These reports
      have contributed to significant concern among healthcare providers and patients
      who are taking statins or are candidates for statin therapy. This review shows
      that the discovery and diagnosis of diabetes during statin therapy are limited to
      patients with multiple pre-existing diabetogenic risk factors, including
      sedentary lifestyle, diabetogenic and obesogenic diet, abdominal obesity,
      metabolic syndrome, hypertension, family history of diabetes, dysglycemia,
      prediabetes, and unrecognized diabetes. Diabetes diagnosed during the course of
      statin therapy is not statin-induced, but is discovered in individuals with pre
      existing diabetogenic risk factors, who would have developed diabetes, with or
      without statin therapy.

PMID- 24569554
TI  - The structure/function of apoprotein A-I mimetic peptides: an update.
AB  - PURPOSE OF REVIEW: To review recent advances in our understanding of the
      mechanism of action of apoprotein A-I (apoA-I) mimetic peptides and improved
      methods for the oral delivery of peptides. RECENT FINDINGS: The apoA-I mimetic
      peptides are based on the structure of the major apoprotein of HDL with the
      expectation that they may also mimic some of the antiatherogenic functions of
      HDL. Recent work has provided insight into mechanisms by which they may be
      antioxidative and anti-inflammatory. In addition, recent work has shifted the
      focus of the site of action of the mimetic peptides to the small intestine from
      the plasma and HDL and suggests modulation of bioactive oxidized lipids in the
      intestine by the peptides may be a major antiatherogenic pathway. The development
      of transgenic tomatoes expressing an apoA-I mimetic peptide is a significant
      advance in the oral delivery of peptides as therapies for cardiovascular disease
      and other chronic inflammatory disorders. SUMMARY: In the past year, there have
      been important advances in the field of apoA-I mimetic peptides, including the
      oral delivery of bioactive peptides. Further work is required to fully understand
      the molecular basis for the effect of the peptide on the intestine and bioactive
      oxidized lipids.

PMID- 24569552
TI  - Type 2 diabetes and cardiovascular disease: what next?
AB  - PURPOSE OF REVIEW: Cardiovascular disease (CVD) is the leading cause of mortality
      in type 2 diabetes mellitus (T2DM), and modifying cardiovascular risk through
      lifestyle intervention and pharmacologic therapy is paramount. This review
      focuses on recent advances in treatment of classical (traditional) cardiovascular
      risk factors and highlights the impact of novel risk factors, including sleep
      disorders, socioeconomic status and chronic psychological stress on CVD in T2DM.
      RECENT FINDINGS: Obesity is a substantial cardiovascular risk factor, and
      recently, large trials of lifestyle and surgical (e.g. gastric bypass)
      interventions impact on CVD in overweight and obese patients have been reported.
      Lifestyle intervention including low calorie diet and exercise reduced individual
      cardiovascular risk factors but did not decrease the rate of long-term
      cardiovascular events. Bariatric surgery was beneficial in reducing
      cardiovascular risk factors and long-term cardiovascular events. Sleep
      insufficiency, poor sleep quality and obstructive sleep apnoea lead to higher CVD
      and further research is needed to characterize the benefit of treating sleep
      disorders on long-term cardiovascular events in T2DM. Lastly, socioeconomic
      status and chronic psychological stress independently have a major impact on
      increasing CVD in T2DM, and public health policies to reduce this burden will be
      important to address over the coming decade. SUMMARY: CVD in T2DM is
      multifactorial and requires a multifaceted approach in reducing known
      cardiovascular risks at the individual patient level through lifestyle,
      pharmacotherapy and surgical interventions and at the societal level through
      public health policies that support reduction in classical and novel
      cardiovascular risk factors.

PMID- 24569565
TI  - Nicotine absorption from electronic cigarette use: comparison between first and
      new-generation devices.
AB  - A wide range of electronic cigarette (EC) devices, from small cigarette-like
      (first-generation) to new-generation high-capacity batteries with electronic
      circuits that provide high energy to a refillable atomizer, are available for
      smokers to substitute smoking. Nicotine delivery to the bloodstream is important
      in determining the addictiveness of ECs, but also their efficacy as smoking
      substitutes. In this study, plasma nicotine levels were measured in experienced
      users using a first- vs. new-generation EC device for 1 hour with an 18 mg/ml
      nicotine-containing liquid. Plasma nicotine levels were higher by 35-72% when
      using the new- compared to the first-generation device. Compared to smoking one
      tobacco cigarette, the EC devices and liquid used in this study delivered one
      third to one-fourth the amount of nicotine after 5 minutes of use. New-generation
      EC devices were more efficient in nicotine delivery, but still delivered nicotine
      much slower compared to tobacco cigarettes. The use of 18 mg/ml nicotine
      concentration liquid probably compromises ECs' effectiveness as smoking
      substitutes; this study supports the need for higher levels of nicotine
      containing liquids (approximately 50 mg/ml) in order to deliver nicotine more
      effectively and approach the nicotine-delivery profile of tobacco cigarettes.

PMID- 24569567
TI  - Coherent analysis of disordered mesoporous adsorbents using small angle X-ray
      scattering and physisorption experiments.
AB  - Characterization of mesoporous adsorbents is traditionally performed in terms of
      the pore size distribution with bulk methods like physisorption and mercury
      intrusion. But their application relies on assumptions regarding the basic pore
      geometry. Although novel tools have enabled the quantitative interpretation of
      physisorption data for adsorbents having a well-defined pore structure the
      analysis of disordered mesoporosity still remains challenging. Here we show that
      small angle X-ray scattering (SAXS) combined with chord length distribution (CLD)
      analysis presents a precise and convenient approach to determine the structural
      properties of two-phase (solid-void) systems of mesopores. Characteristic wall
      (solid) and pore (void) sizes as well as surface areas are extracted without the
      need to assume a certain pore shape. The mesoporous structure of modern,
      commercially available fully porous and core-shell adsorbent particles is
      examined by SAXS/CLD analysis. Mean pore size and surface area are compared with
      results obtained from nitrogen physisorption data and show excellent agreement. 

PMID- 24569566
TI  - Stomach microbiota composition varies between patients with non-atrophic
      gastritis and patients with intestinal type of gastric cancer.
AB  - We aimed to characterize microbiota of the gastric mucosa as it progress to
      intestinal type of cancer. Study included five patients each of non-atrophic
      gastritis (NAG), intestinal metaplasia (IM) and intestinal-type gastric cancer
      (GC). Gastric tissue was obtained and DNA extracted for microbiota analyses using
      the microarray G3 PhyloChip. Bacterial diversity ranged from 8 to 57, and
      steadily decreased from NAG to IM to GC (p = 0.004). A significant microbiota
      difference was observed between NAG and GC based on Unifrac-presence/absence and
      weighted-Unifrac-abundance metrics of 283 taxa (p < 0.05). HC-AN analyses based
      on presence/absence of 238 taxa revealed that GC and NAG grouped apart, whereas
      IM overlapped with both. An ordinated analyses based on weighted-Unifrac distance
      given abundance of 44 taxa showing significance across categories revealed
      significant microbiota separation between NAG and GC. This study is the first to
      show a gradual shift in gastric microbiota profile from NAG to IM to GC. 

PMID- 24569569
TI  - Group training in interpersonal problem-solving skills for workplace adaptation
      of adolescents and adults with Asperger syndrome: a preliminary study.
AB  - Adults with Asperger syndrome show persistent difficulties in social situations
      which psychosocial treatments may address. Despite the multiple studies focusing
      on social skills interventions, only some have focused specifically on problem
      solving skills and have not targeted workplace adaptation training in the adult
      population. This study describes preliminary data from a group format manual
      based intervention, the Interpersonal Problem-Solving for Workplace Adaptation
      Programme, aimed at improving the cognitive and metacognitive process of social
      problem-solving skills focusing on typical social situations in the workplace
      based on mediation as the main strategy. A total of 50 adults with Asperger
      syndrome received the programme and were compared with a control group of typical
      development. The feasibility and effectiveness of the treatment were explored.
      Participants were assessed at pre-treatment and post-treatment on a task of
      social problem-solving skills and two secondary measures of socialisation and
      work profile using self- and caregiver-report. Using a variety of methods, the
      results showed that scores were significantly higher at post-treatment in the
      social problem-solving task and socialisation skills based on reports by parents.
      Differences in comparison to the control group had decreased after treatment. The
      treatment was acceptable to families and subject adherence was high. The
      Interpersonal Problem-Solving for Workplace Adaptation Programme appears to be a
      feasible training programme. 

PMID- 24569570
TI  - Mutations of isocitrate dehydrogenase 1 and 2 in intrahepatic cholangiocarcinoma.
AB  - PURPOSE OF REVIEW: Exome sequencing studies have recently expanded the genetic
      characterization of intrahepatic cholangiocarcinomas. Among a number of novel
      genes, isocitrate dehydrogenase (IDH) is recurrently mutated in intrahepatic
      cholangiocarcinomas. We review the effects of these mutations on several
      biochemical pathways, as well as potential changes to downstream signaling
      pathways. RECENT FINDINGS: Hotspot mutations in IDH isoforms 1 or 2 occur in
      approximately 15% of intrahepatic cholangiocarcinomas. These mutations result in
      elevated levels of an oncometabolite, 2-hydroxyglutarate, which is associated
      with higher DNA CpG methylation and altered histone methylation that accompany a
      block in cellular differentiation. Exploratory studies have suggested additional
      phenotypes associated with IDH1/2 mutations. SUMMARY: Tumors with IDH1 or IDH2
      mutations may represent a distinct subtype of cholangiocarcinomas. Further
      studies are required to elucidate the exact role that mutant IDH1/2 and 2
      hydroxyglutarate play in tumorigenesis, and what are the best strategies to
      target these tumor types.

PMID- 24569571
TI  - Bio-barcode gel assay for microRNA.
AB  - MicroRNA has been identified as a potential biomarker because expression level of
      microRNA is correlated with various cancers. Its detection at low concentrations
      would be highly beneficial for cancer diagnosis. Here, we develop a new type of a
      DNA-modified gold nanoparticle-based bio-barcode assay that uses a conventional
      gel electrophoresis platform and potassium cyanide chemistry and show this assay
      can detect microRNA at aM levels without enzymatic amplification. It is also
      shown that single-base-mismatched microRNA can be differentiated from perfectly
      matched microRNA and the multiplexed detection of various combinations of
      microRNA sequences is possible with this approach. Finally, differently expressed
      microRNA levels are selectively detected from cancer cells using the bio-barcode
      gel assay, and the results are compared with conventional polymerase chain
      reaction-based results. The method and results shown herein pave the way for
      practical use of a conventional gel electrophoresis for detecting biomolecules of
      interest even at aM level without polymerase chain reaction amplification. 

PMID- 24569572
TI  - Predictors of 30-day and 1-year mortality after transvenous lead extraction: a
      single-centre experience.
AB  - AIMS: Owing to the increasing use of cardiac implantable electronic devices,
      there is a growing need for safe and effective techniques to manage device
      related complications and lead dysfunction. Lead extraction remains a challenging
      procedure with inherent risks. We present the 30-day and long-term outcomes of
      lead extractions in the University Hospitals Leuven. METHODS AND RESULTS: We
      report a retrospective cohort study of 176 patients admitted to the University
      Hospitals Leuven between January 2005 and December 2011, for the transvenous
      extraction of 295 leads. Indications for extraction were lead dysfunction and
      device upgrade in 84 (47.7%), pocket infection in 61 (34.7%), and systemic
      infection in 31 patients (17.6%). Extraction was successful in 95.5% of patients
      with complete removal of the leads or only a minor fragment remaining. One fatal
      peri-procedural complication occurred. Thirty-day mortality was 3.4% (n = 6).
      Systemic infection was the only significant predictor of 30-day mortality [odds
      ratio (OR) 29.706; P = 0.029]. A lower level of haemoglobin prior to extraction
      also tended to be related with a higher mortality, but this was not significant
      (OR 2.024; P = 0.082). One-year mortality was 8.5% (n = 15). Systemic infection
      (OR 9.727; P = 0.009), a lower level of haemoglobin (OR 1.597; P = 0.05), and a
      higher level of ureum (OR 1.021; P = 0.017) prior to extraction were significant
      predictors of 1-year mortality. Systemic infection was associated with
      significantly higher 30-day (19%), 1-year (32%), and long-term (39%) mortality
      rates. CONCLUSION: Lead extraction can be safely and successfully performed in
      the majority of patients, with limited life-threatening complications. However,
      lead extraction because of systemic infection is associated with a significantly
      higher risk of short- and long-term mortality.

PMID- 24569573
TI  - The predictive value of echocardiographic parameters associated with left
      ventricular diastolic dysfunction on short- and long-term outcomes of catheter
      ablation of atrial fibrillation.
AB  - AIMS: Recurrence of atrial fibrillation (AF) is frequently observed after AF
      catheter ablation. However, the predictive value of echocardiographic parameters
      associated with left ventricular diastolic dysfunction (LVDD) has not been well
      studied. METHODS AND RESULTS: In 124 consecutive patients (mean age 61 +/- 10
      years, 60% male) with paroxysmal (n = 70) or persistent AF (n = 54) undergoing AF
      catheter ablation, mitral early diastolic peak (E-wave) and late peak (A-wave)
      velocities, E/A ratio, deceleration time (DT) of mitral early velocity, early
      diastolic mitral annulus peak velocity (e'), and E/e' ratio were determined by
      transthoracic echocardiography. Early (ERAF) and late AF recurrence (LRAF) were
      monitored with 7-day Holter electrocardiograms directly after catheter ablation
      and after 6 and 12 months. Early AF recurrence occurred in 34% of the patients,
      while LRAF was observed in 27% of the patients. Patients with ERAF had higher E
      wave (0.9 +/- 0.2 vs. 0.8 +/- 0.2 m/s, P = 0.035) and lower A-wave velocity (0.5
      +/- 0.2 vs. 0.6 +/- 0.2 m/s, P = 0.038), higher E/A ratio (1.8 +/- 0.9 vs. 1.5 +/
      0.9, P = 0.089), and slower DT (214 +/- 67 vs. 243 +/- 68 ms, P = 0.073), while
      E/e', left atrial diameter, and left ventricular ejection fraction were similar.
      In multivariable regression analysis, the E/A ratio was the only independent
      predictor of ERAF (odds ratio 2.905, 95% confidence interval 1.072-7.870, P =
      0.036). None of the echocardiographic parameters influenced the late therapy
      outcome. CONCLUSION: Early results of the catheter ablation, but not the late
      rhythm outcome, are influenced by an impaired mitral inflow pattern, which is
      associated with LVDD.

PMID- 24569574
TI  - The sustainable growth rate: a 2014 update.

PMID- 24569575
TI  - ADAPT FAST study: a direct aspiration first pass technique for acute stroke
      thrombectomy.
AB  - BACKGROUND: The development of new revascularization devices has improved
      recanalization rates and time, but not clinical outcomes. We report a
      prospectively collected clinical experience with a new technique utilizing a
      direct aspiration first pass technique with large bore aspiration catheter as the
      primary method for vessel recanalization. METHODS: 98 prospectively identified
      acute ischemic stroke patients with 100 occluded large cerebral vessels at six
      institutions were included in the study. The ADAPT technique was utilized in all
      patients. Procedural and clinical data were captured for analysis. RESULTS: The
      aspiration component of the ADAPT technique alone was successful in achieving
      Thrombolysis in Cerebral Infarction (TICI) 2b or 3 revascularization in 78% of
      cases. The additional use of stent retrievers improved the TICI 2b/3
      revascularization rate to 95%. The average time from groin puncture to at least
      TICI 2b recanalization was 37 min. A 5MAX demonstrated similar success to a 5MAX
      ACE in achieving TICI 2b/3 revascularization alone (75% vs 82%, p=0.43). Patients
      presented with an admitting median National Institutes of Health Stroke Scale
      (NIHSS) score of 17.0 (12.0-21.0) and improved to a median NIHSS score at
      discharge of 7.3 (1.0-11.0). Ninety day functional outcomes were 40% (modified
      Rankin Scale (mRS) 0-2) and 20% (mRS 6). There were two procedural complications
      and no symptomatic intracerebral hemorrhages. DISCUSSION: The ADAPT technique is
      a fast, safe, simple, and effective method that has facilitated our approach to
      acute ischemic stroke thrombectomy by utilizing the latest generation of large
      bore aspiration catheters to achieve previously unparalleled angiographic
      outcomes.

PMID- 24569577
TI  - Pathologically reduced subbasal nerve density in epithelial basement membrane
      dystrophy is unaltered by phototherapeutic keratectomy treatment.
AB  - PURPOSE: To investigate the effect of phototherapeutic keratectomy (PTK)
      treatment on corneal epithelial wing cell and corneal subbasal nerve density in
      epithelial basement membrane dystrophy (EBMD). METHODS: A total of 39 patients
      with EBMD who underwent PTK treatment, 40 healthy volunteers, and 24 untreated
      eyes with EBMD were examined with laser-scanning in vivo confocal microscopy
      (IVCM). Corneal subbasal nerves and epithelial wing cells were manually
      quantified from IVCM images by two observers, while epithelial wing cells were
      additionally quantified by a fully automated method. RESULTS: Subbasal nerve
      density was significantly reduced in untreated (10,164 +/- 4139 MUm/mm(2); n =
      24) and PTK-treated (10,624 +/- 4479 MUm/mm(2); n = 39) EBMD eyes, relative to
      healthy controls (18,241 +/- 4479 MUm/mm(2); n = 40) (P < 0.001). Subbasal nerve
      density in PTK-treated and untreated eyes did not differ (P > 0.05). Epithelial
      wing cell density did not differ between PTK-treated and untreated EBMD eyes, by
      either manual or automated analysis; however, epithelial wing cell density in PTK
      treated EBMD corneas was significantly reduced (P = 0.008) relative to healthy
      corneas, by automated cell counting. CONCLUSIONS: Subbasal nerve density in EBMD
      is reduced by 45% and recovers only to the reduced level in the long term after
      PTK treatment, whereas epithelial wing cell density in EBMD is not affected by
      PTK in the long term. Fully automated cell analysis from IVCM images could
      provide an objective, standardized means to quantify and compare corneal cell
      densities in future studies.

PMID- 24569576
TI  - Quantifying disrupted outer retinal-subretinal layer in SD-OCT images in
      choroidal neovascularization.
AB  - PURPOSE: We reported a fully automated method to identify and quantify the
      thickness of the outer retinal-subretinal (ORSR) layer from clinical spectral
      domain optical coherence tomography (SD-OCT) scans of choroidal
      neovascularization (CNV) due to exudative age-related macular degeneration
      (eAMD). METHODS: A total of 23 subjects with CNV met eligibility. Volumetric SD
      OCT scans of 23 eyes were obtained (Zeiss Cirrus, 200 * 200 * 1024 voxels). In a
      subset of eyes, scans were repeated. The OCT volumes were analyzed using our
      standard parameters and using a 3-dimensional (3D) graph-search approach with an
      adaptive cost function. A retinal specialist graded the segmentation as generally
      accurate, local segmentation inaccuracies, or failure. Reproducibility on repeat
      scans was analyzed using root mean square coefficient of variation (RMS CV) of
      the average ORSR thickness. RESULTS: Using a standard segmentation approach, 1/23
      OCT segmentations was graded generally accurate and 22/23 were failure(s). With
      the adaptive method 21/23 segmentations were graded generally accurate; 2/23 were
      local segmentation inaccuracies and none was a failure. The intermethod quality
      of segmentation was significantly different (P << 0.001). The average ORSR
      thickness measured on CNV patients (78.0 MUm; 95% confidence interval [CI], 72.5
      83.4 MUm) is significantly larger (P << 0.001) than normal average ORSR layer
      thickness (51.5 +/- 3.3 MUm). The RMS CV was 8.1%. CONCLUSIONS: We have developed
      a fully automated 3D method for segmenting the ORSR layer in SD-OCT of patients
      with CNV from eAMD. Our method can quantify the ORSR layer thickness in the
      presence of fluid, which has the potential to augment management accuracy and
      efficiency of anti-VEGF treatment.

PMID- 24569578
TI  - Circadian pattern of intraocular pressure fluctuations in young myopic eyes with
      open-angle glaucoma.
AB  - PURPOSE: To characterize the circadian pattern of habitual-position intraocular
      pressure (IOP) and its association with ocular dimension in young myopic patients
      with open-angle glaucoma (OAG). METHODS: A total of 108 young OAG patients with
      moderate to severe myopia (myopia group) and 67 age-matched OAG patients with
      emmetropia or mild myopia (control group) were recruited prospectively over 3
      years. IOP was recorded 11 times over a 24-hour period by a single, well-trained
      ophthalmology resident using a handheld tonometer. RESULTS: A total of 87 men and
      88 women were included in this study. Analysis of the entire myopia group
      indicated no acrophase in habitual-position IOP over 24 hours. Subgroup analysis
      indicated that 44 patients (40.7%) had a diurnal acrophase, 17 patients (15.7%)
      had a nocturnal acrophase, and 47 patients (43.6%) had no evident acrophase. By
      contrast, the control group showed an overall nocturnal acrophase in habitual
      position IOP, with 14 patients (20.8%) having a diurnal acrophase, 30 patients
      (44.8%) having a nocturnal acrophase, and 23 patients (34.4%) having no evident
      acrophase in subgroup analysis. There was a negative correlation between
      nocturnal habitual-position IOP elevation and axial length in the overall
      population. CONCLUSIONS: In young myopic OAG eyes, there is no significant
      nocturnal elevation in habitual-position IOP, while IOP increases at night-time
      in age-matched control eyes. The overall 24-hour IOP pattern in the myopia group
      did not show an acrophase. Finally, data showed a negative relationship between
      nocturnal habitual-position IOP elevation and axial length.

PMID- 24569579
TI  - Evidence of lipid degradation during overnight contact lens wear: gas
      chromatography mass spectrometry as the diagnostic tool.
AB  - PURPOSE: We investigated structural differences in the fatty acid profiles of
      lipids extracted from ex vivo contact lenses by using gas chromatography mass
      spectrometry (GCMS). Two lens materials (balafilcon A or lotrafilcon A) were worn
      on a daily or continuous wear schedule for 30 and 7 days. METHODS: Lipids from
      subject-worn lenses were extracted using 1:1 chloroform: methanol and
      transmethylated using 5% sulfuric acid in methanol. Fatty acid methyl esters
      (FAMEs) were collected using hexane and water, and analyzed by GCMS (Varian 3800
      GC, Saturn 2000 MS). RESULTS: The gas chromatograms of lens extracts that were
      worn on a continuous wear schedule showed two predominant peaks, C16:0 and C18:0,
      both of which are saturated fatty acids. This was the case for balafilcon A and
      lotrafilcon A lenses. However, the gas chromatograms of lens extracts that were
      worn on a daily wear schedule showed saturated (C16:0, C18:0) and unsaturated
      (C16:1 and C18:1) fatty acids. CONCLUSIONS: Unsaturated fatty acids are degraded
      during sleep in contact lenses. Degradation occurred independently of lens
      material or subject-to-subject variability in lipid deposition. The consequences
      of lipid degradation are the production of oxidative products, which may be
      linked to contact lens discomfort.

PMID- 24569581
TI  - Association of serum lipids with macular thickness and volume in type 2 diabetes
      without diabetic macular edema.
AB  - PURPOSE: To assess the relationship between macular thickness and volume as
      characterized by optical coherence tomography (OCT) and known risk factors for
      diabetic retinopathy (DR) or macular edema (DME) in type 2 diabetic patients with
      no DME. METHODS: Seventy-four patients with type 2 diabetes without DME and no or
      only minimal DR (n = 67 with no DR; n = 7 with minimal DR; mean age, 59.5 years)
      were recruited at a tertiary eye hospital. Central subfield macular thickness
      (CSMT; circle of 500-MUm radius) and central subfield macular volume (CSMV) were
      measured using spectral-domain OCT. Associations between OCT parameters and known
      risk factors for DR were examined using multiple linear regression models.
      RESULTS: The mean CSMT and CSMV values were 273.7 +/- 17.8 MUm and 0.215 +/-
      0.015 mm(3), respectively. After adjusting for age, sex, duration of diabetes,
      hemoglobin A1c, and urine protein, low-density lipoprotein (LDL) cholesterol was
      positively associated with CSMT and CSMV; each 1 mmol/L increase in LDL was
      associated with a mean increase in CSMT of 6.52 MUm (95% confidence interval
      [CI], 1.96-11.08; P = 0.006) and a mean increase in CSMV of 0.0047 mm(3) (95% CI,
      0.001-0.0085; P = 0.015). CONCLUSIONS: A higher LDL cholesterol level was
      associated with increased CSMT and CSMV in diabetic patients without DME.
      Prospective longitudinal studies are warranted to assess whether having both
      elevated levels of LDL and higher CSMT or CSMV is a risk indicator for subsequent
      development of DME.

PMID- 24569580
TI  - Rapid automated diagnosis of diabetic peripheral neuropathy with in vivo corneal
      confocal microscopy.
AB  - PURPOSE: To assess the diagnostic validity of a fully automated image analysis
      algorithm of in vivo confocal microscopy images in quantifying corneal subbasal
      nerves to diagnose diabetic neuropathy. METHODS: One hundred eighty-six patients
      with type 1 and type 2 diabetes mellitus (T1/T2DM) and 55 age-matched controls
      underwent assessment of neuropathy and bilateral in vivo corneal confocal
      microscopy (IVCCM). Corneal nerve fiber density (CNFD), branch density (CNBD),
      and length (CNFL) were quantified with expert, manual, and fully-automated
      analysis. The areas under the curve (AUC), odds ratios (OR), and optimal
      thresholds to rule out neuropathy were estimated for both analysis methods.
      RESULTS: Neuropathy was detected in 53% of patients with diabetes. A significant
      reduction in manual and automated CNBD (P < 0.001) and CNFD (P < 0.0001), and
      CNFL (P < 0.0001) occurred with increasing neuropathic severity. Manual and
      automated analysis methods were highly correlated for CNFD (r = 0.9, P < 0.0001),
      CNFL (r = 0.89, P < 0.0001), and CNBD (r = 0.75, P < 0.0001). Manual CNFD and
      automated CNFL were associated with the highest AUC, sensitivity/specificity and
      OR to rule out neuropathy. CONCLUSIONS: Diabetic peripheral neuropathy is
      associated with significant corneal nerve loss detected with IVCCM. Fully
      automated corneal nerve quantification provides an objective and reproducible
      means to detect human diabetic neuropathy.

PMID- 24569583
TI  - Remote ischemia influences the responsiveness of the retina: observations in the
      rat.
AB  - PURPOSE: Remote ischemic preconditioning (RIP) has been found to be protective of
      heart and brain against ischemic injury. We have tested the effects of RIP on
      retinal function using the electroretinogram. METHODS: Ischemia remote from the
      retina was induced in one hindlimb, using a pressure cuff applied for between 5
      and 10 minutes. A temperature probe on the footpad confirmed blockage of the
      circulation. To test the impact of RIP on retinal function, we recorded the dark
      adapted flash electroretinogram (ERG) in four groups (n = 5 per group) of Sprague
      Dawley rats (sham, 5-minute, 10-minute, and 2 * 5-minute ischemia). Heart rate,
      breath rate, and peripheral oxygen saturation were monitored using infrared pulse
      oximetry. RESULTS: RIP increased both the a- and b-waves by up to 14%, more
      markedly after the longer periods (10 minutes or 2 * 5 minutes) of ischemia. The
      effect was tested up to 30 minutes after ischemia and retested at 1 week and 1
      month. RIP did not appear to accelerate the initial stages of recovery from
      photopigment bleach. Systemic oxygen saturation, heart rate, and respiration did
      not vary consistently during or after remote ischemia. CONCLUSIONS: The effect of
      RIP on the ERG is a novel finding. Possible mechanisms of this effect are
      discussed and related to the idea of neuroprotection and to fundamentals of the
      electroretinogram.

PMID- 24569582
TI  - Photoreceptor cells with profound structural deficits can support useful vision
      in mice.
AB  - PURPOSE: In animal models of degenerative photoreceptor disease, there has been
      some success in restoring photoreception by transplanting stem cell-derived
      photoreceptor cells into the subretinal space. However, only a small proportion
      of transplanted cells develop extended outer segments, considered critical for
      photoreceptor cell function. The purpose of this study was to determine whether
      photoreceptor cells that lack a fully formed outer segment could usefully
      contribute to vision. METHODS: Retinal and visual function was tested in wild
      type and Rds mice at 90 days of age (Rds(P90)). Photoreceptor cells of mice
      homozygous for the Rds mutation in peripherin 2 never develop a fully formed
      outer segment. The electroretinogram and multielectrode recording of retinal
      ganglion cells were used to test retinal responses to light. Three distinct
      visual behaviors were used to assess visual capabilities: the optokinetic
      tracking response, the discrimination-based visual water task, and a measure of
      the effect of vision on wheel running. RESULTS: Rds(P90) mice had reduced but
      measurable electroretinogram responses to light, and exhibited light-evoked
      responses in multiple types of retinal ganglion cells, the output neurons of the
      retina. In optokinetic and discrimination-based tests, acuity was measurable but
      reduced, most notably when contrast was decreased. The wheel running test showed
      that Rds(P90) mice needed 3 log units brighter luminance than wild type to
      support useful vision (10 cd/m(2)). CONCLUSIONS: Photoreceptors that lack fully
      formed outer segments can support useful vision. This challenges the idea that
      normal cellular structure needs to be completely reproduced for transplanted
      cells to contribute to useful vision.

PMID- 24569584
TI  - Early corneal nerve damage and recovery following small incision lenticule
      extraction (SMILE) and laser in situ keratomileusis (LASIK).
AB  - PURPOSE: We compared early corneal nerve changes after small incision lenticule
      extraction (SMILE) and laser in situ keratomileusis (LASIK). METHODS: A total of
      12 rabbits underwent LASIK in one eye and SMILE in the fellow eye. Baseline and
      follow-up evaluations at 1, 2, and 4 weeks postoperatively were performed with in
      vivo confocal microscopy to evaluate 5 different areas within the treated zone:
      center, superior, inferior, nasal, and temporal. Cryosections of the corneas and
      whole mount of the extracted SMILE lenticules were analyzed with immunostaining
      of betaIII-tubulin. RESULTS: One week after SMILE and LASIK, a decrease in nerve
      length and density was observed in all evaluated areas. A trend toward greater
      subbasal nerve length and density (SLD), more eyes with subbasal nerves (ESN),
      more eyes with subbasal nerves longer than 200 MUm (SNL), and higher mean number
      of subbasal nerves by frame (NSN) in SMILE than in LASIK groups was observed at
      subsequent follow-up time points. Only the SMILE group showed a recovery of SLD,
      ESN, and NSN by week 4 (P > 0.05). A trend toward more eyes with sprouting
      subbasal nerves and greater mean number of sprouting nerves was observed in LASIK
      than in SMILE, indicating that more subbasal nerves were disrupted and undergoing
      regeneration after LASIK. Immunostaining at postoperative week 4 revealed a
      faster stromal nerve recovery in post-SMILE eyes compared to post-LASIK eyes.
      CONCLUSIONS: Our findings suggest that SMILE results in less nerve damage and
      faster nerve recovery than LASIK.

PMID- 24569585
TI  - Quantitative analysis of fluorescence lifetime measurements of the macula using
      the fluorescence lifetime imaging ophthalmoscope in healthy subjects.
AB  - PURPOSE: Fundus autofluorescence (FAF) cannot only be characterized by the
      intensity or the emission spectrum, but also by its lifetime. As the lifetime of
      a fluorescent molecule is sensitive to its local microenvironment, this technique
      may provide more information than fundus autofluorescence imaging. We report here
      the characteristics and repeatability of FAF lifetime measurements of the human
      macula using a new fluorescence lifetime imaging ophthalmoscope (FLIO). METHODS:
      A total of 31 healthy phakic subjects were included in this study with an age
      range from 22 to 61 years. For image acquisition, a fluorescence lifetime
      ophthalmoscope based on a Heidelberg Engineering Spectralis system was used.
      Fluorescence lifetime maps of the retina were recorded in a short- (498-560 nm)
      and a long- (560-720 nm) spectral channel. For quantification of fluorescence
      lifetimes a standard ETDRS grid was used. RESULTS: Mean fluorescence lifetimes
      were shortest in the fovea, with 208 picoseconds for the short-spectral channel
      and 239 picoseconds for the long-spectral channel, respectively. Fluorescence
      lifetimes increased from the central area to the outer ring of the ETDRS grid.
      The test-retest reliability of FLIO was very high for all ETDRS areas (Spearman's
      rho = 0.80 for the short- and 0.97 for the long-spectral channel, P < 0.0001).
      Fluorescence lifetimes increased with age. CONCLUSIONS: The FLIO allows
      reproducible measurements of fluorescence lifetimes of the macula in healthy
      subjects. By using a custom-built software, we were able to quantify fluorescence
      lifetimes within the ETDRS grid. Establishing a clinically accessible standard
      against which to measure FAF lifetimes within the retina is a prerequisite for
      future studies in retinal disease.

PMID- 24569586
TI  - The Epstein-Barr virus causes epithelial-mesenchymal transition in human corneal
      epithelial cells via Syk/src and Akt/Erk signaling pathways.
AB  - PURPOSE: Although Epstein-Barr virus (EBV)-associated keratitis is rare, it can
      cause acute corneal necrosis and neovascularization. We aimed to examine the
      signaling mechanism by which EBV causes epithelial-mesenchymal transition (EMT)
      in human corneal epithelial cells (HCECs) in vitro. METHODS: The cellular
      response to EBV was assessed by real-time PCR, Western blot, migration assay,
      invasion assay, inhibitor assay, and ELISA assay. RESULTS: A model of EBV-induced
      EMT was established in HCECs. The EBV induced morphologic changes in the cells;
      the loss of epithelial markers E-cadherin, ZO-1, and beta-catenin; and an
      increase in the mesenchymal markers N-cadherin, Vimentin, Snail, and TCF8/Zeb1.
      The EBV infection also led to the nuclear translocation of Snail and TCF8/Zeb1;
      enhanced the secretion of IL-6, IL-8, VEGF, TGF-beta1, TNF-alpha, and MCP-1; and
      upregulated the expression of MMP2 and MMP9. The EBV-infected HCECs exhibited
      increased migration and invasiveness compared to uninfected HCECs. We measured
      the involvement of Syk, Src, PI3K/Akt, and Erk signaling, but not Smad, in EMT by
      EBV-induced TGF-beta1. We demonstrated that treatment with TGF-beta1, TGF-beta
      receptors, Syk, or Src inhibitor blocked TGF-beta1, Syk, or Src signaling
      activation, and EMT development by EBV. Moreover, these inhibitors prevented
      PI3K/Akt and Erk activation. CONCLUSIONS: An EBV infection in HCECs can lead to a
      mesenchymal fibroblast-like morphology, and cause EMT through the activation of
      PI3K/Akt and Erk by TGF-beta1-mediated Syk and Src signaling. This phenomenon may
      have implications for EBV-associated keratitis and molecular approaches to
      treatment.

PMID- 24569587
TI  - Mitochondrial sequence changes in keratoconus patients.
AB  - PURPOSE: We investigated whether a group of patients with keratoconus (KTCN)
      harbor mutations in the mitochondrial genome. METHODS: We sequenced the full
      mitochondrial genome in a group of Saudi patients with KTCN (n = 26) and 100
      ethnically matched controls who had no KTCN by examination. RESULTS: A total of
      10 KTCN patients (38.5%) had potentially pathogenic nonsynonymous mtDNA
      mutations. Of the nonsynonymous sequence changes detected, 4 (40%) were in
      Complex I, one was in the tRNA(Glutamine), one was in tRNA(Tryptophan), one was
      in tRNA(Asparagine), one was in tRNA(Histidine), and two were in the
      tRNA(Leucine2). One nonsynonymous sequence change was heteroplasmic, whereas all
      the remaining 9 were homoplasmic. These sequence changes were not detected in
      controls of similar ethnicity. Four sequence changes were novel (were not
      reported previously) and 5 were reported previously. Additionally, we detected 54
      synonymous (does not result in an amino acid change) sequence changes with no
      pathologic significance. CONCLUSIONS: If our results are confirmed in a larger
      cohort and multiple ethnicities, then mtDNA mutation may be considered as a
      genetic risk factor contributing indirectly through the oxidative stress
      mechanism to the development and/or progression of KTCN.

PMID- 24569589
TI  - Challenges and methodology for testing young healthy women in physiological
      studies.
AB  - Physiological responses and control of body systems differ between women and men.
      Moreover, within women, female gonadal hormones have important influences on
      organs and systems outside of reproduction. Until the NIH Revitalization Act of
      1993, laboratories focused physiological research primarily on men, and this
      focus placed limitations on women's health care. Thus, the NIH directive to
      include women required scientists and physicians studying humans to consider
      female reproductive physiology. Even though this directive was enacted over 20
      years ago, there is still a great deal of misunderstanding as to the best methods
      to control hormones or account for changes in internal hormone exposure in women.
      This discussion describes common methods investigators use to include women in
      physiological studies and to examine the impact of female reproductive hormone
      exposure for research purposes. In some cases, the goal is to control for phase
      of the cycle, so women are studied when the endogenous hormones should be similar
      to each other. When the goal of the research is to examine the effects of
      hormones on a physiological response, it is important to use methods that will
      change hormone exposure in a controlled fashion. We recommend a method that
      employs gonadotropin-releasing hormone (GnRH) agonist or antagonist to suppress
      estrogens, gonadotropins, progesterone, and androgens followed by administration
      of these hormones. While this method is more invasive, it is safe and is the
      strongest research design to examine both hormone effects within women and
      between women and men.

PMID- 24569590
TI  - Reduced nocturnal ACTH-driven cortisol secretion during critical illness.
AB  - Recently, during critical illness, cortisol metabolism was found to be reduced.
      We hypothesize that such reduced cortisol breakdown may suppress pulsatile ACTH
      and cortisol secretion via feedback inhibition. To test this hypothesis,
      nocturnal ACTH and cortisol secretory profiles were constructed by deconvolution
      analysis from plasma concentration time series in 40 matched critically ill
      patients and eight healthy controls, excluding diseases or drugs that affect the
      hypothalamic-pituitary-adrenal axis. Blood was sampled every 10 min between 2100
      and 0600 to quantify plasma concentrations of ACTH and (free) cortisol.
      Approximate entropy, an estimation of process irregularity, cross-approximate
      entropy, a measure of ACTH-cortisol asynchrony, and ACTH-cortisol dose-response
      relationships were calculated. Total and free plasma cortisol concentrations were
      higher at all times in patients than in controls (all P < 0.04). Pulsatile
      cortisol secretion was 54% lower in patients than in controls (P = 0.005),
      explained by reduced cortisol burst mass (P = 0.03), whereas cortisol pulse
      frequency (P = 0.35) and nonpulsatile cortisol secretion (P = 0.80) were
      unaltered. Pulsatile ACTH secretion was 31% lower in patients than in controls (P
      = 0.03), again explained by a lower ACTH burst mass (P = 0.02), whereas ACTH
      pulse frequency (P = 0.50) and nonpulsatile ACTH secretion (P = 0.80) were
      unchanged. ACTH-cortisol dose response estimates were similar in patients and
      controls. ACTH and cortisol approximate entropy were higher in patients (P <=
      0.03), as was ACTH-cortisol cross-approximate entropy (P <= 0.001). We conclude
      that hypercortisolism during critical illness coincided with suppressed pulsatile
      ACTH and cortisol secretion and a normal ACTH-cortisol dose response. Increased
      irregularity and asynchrony of the ACTH and cortisol time series supported non
      ACTH-dependent mechanisms driving hypercortisolism during critical illness.

PMID- 24569591
TI  - Hypoxia-mediated carbohydrate metabolism and transport promote early-stage murine
      follicle growth and survival.
AB  - Oxygen tension is critical for follicle growth and metabolism, especially for
      early-stage follicles, where vascularity is limited. Its role and underlying
      mechanism in the in vitro activation and maturation of immature to ovulatory
      follicles is largely unknown. In this study, early secondary (110 MUm) murine
      follicles were isolated and encapsulated in alginate hydrogels to replicate the
      in vivo environment of the growing/maturing follicle. Encapsulated follicles were
      cultured for 8 days at either 2.5 or 20% O2. Survival (2.6-fold) and growth (1.2
      fold) were significantly higher for follicles cultured at 2.5% compared with 20%
      O2. Using a mouse hypoxia-signaling pathway qRT-PCR array and GeneGo Metacore
      analysis, we found that direct target genes of the hypoxia-activated HIF1-complex
      were significantly upregulated in follicles cultured for 8 days at 2.5% compared
      with 20% O2, including the carbohydrate transport and metabolism genes Slc2a3,
      Vegfa, Slc2a1, Edn1, Pgk1, Ldha, and Hmox1. Other upregulated genes included
      carbohydrate transporters (Slc2a1, Slc2a3, and Slc16a3) and enzymes essential for
      glycolysis (Pgk1, Hmox1, Hk2, Gpi1, Pfkl, Pfkp, Aldoa, Gapdh, Pgam1, Eno1, Pkm2,
      and Ldha). For follicles cultured at 2.5% O2, a 7.2-fold upregulation of Vegfa
      correlated to an 18-fold increase in VEGFA levels, and a 3.2-fold upregulation of
      Ldha correlated to a 4.8-fold increase in lactate levels. Both VEGFA and lactate
      levels were significantly higher in follicles cultured at 2.5% compared with 20%
      O2. Therefore, enhanced hypoxia-mediated glycolysis is essential for growth and
      survival of early secondary follicles and provides vital insights into improving
      in vitro culture conditions.

PMID- 24569593
TI  - Viral expression of insulin-like growth factor I E-peptides increases skeletal
      muscle mass but at the expense of strength.
AB  - Insulin-like growth factor I (IGF-I) is a protein that regulates and promotes
      growth in skeletal muscle. The IGF-I precursor polypeptide contains a COOH
      terminal extension called the E-peptide. Alternative splicing in the rodent
      produces two isoforms, IA and IB, where the mature IGF-I in both isoforms is
      identical yet the E-peptides, EA and EB, share less than 50% homology. Recent in
      vitro studies show that the E-peptides can enhance IGF-I signaling, leading to
      increased myoblast cell proliferation and migration. To determine the
      significance of these actions in vivo and to evaluate if they are physiologically
      beneficial, EA and EB were expressed in murine skeletal muscle via viral vectors.
      The viral constructs ensured production of E-peptides without the influence of
      additional IGF-I through an inactivating mutation in mature IGF-I. E-peptide
      expression altered ERK1/2 and Akt phosphorylation and increased satellite cell
      proliferation. EB expression resulted in significant muscle hypertrophy that was
      IGF-I receptor dependent. However, the increased mass was associated with a loss
      of muscle strength. EA and EB have similar effects in skeletal muscle signaling
      and on satellite cells, but EB is more potent at increasing muscle mass. Although
      sustained EB expression may drive hypertrophy, there are significant
      physiological consequences for muscle.

PMID- 24569595
TI  - Conformational interchange of a carbohydrate by mechanical compression at the air
      water interface.
AB  - Methyl xylopyranoside containing three 4-(pyrene-1-yl)benzoyl groups (PyXy)
      undergoes conformational interchange within a Langmuir monolayer upon mechanical
      compression. This xylose-type molecular machine PyXy was immobilized within two
      different matrix lipids, methyl stearate and methyl 2,3,4-tri-O-stearoyl-beta-D
      xylopyranoside, which respectively form rigid and soft monolayers. Structural
      properties of the monolayer were characterized by assessing the compressibility,
      compression modulus, and ideal limiting molecular area of PyXy, all of which were
      estimated from the pi-A isotherm measurements. Only the rigid monolayer exhibited
      a transition to the condensed phase with a limiting molecular area of PyXy
      smaller than that of the cross-sectional area of the xylopyranose ring in its C1
      chair conformation. This suggests conformational interchange of PyXy from the
      most stable (4)C1 (C1) form to the metastable (1)C4 (1C) form. Surface-reflective
      fluorescence spectroscopy of the monolayer was applied to detect excimer emission
      resulting from the face-to-face dimerization of pyrenes attached at the O-2 and O
      4 positions of xylose. Fluorescence intensity of the excimer increased abruptly
      in the condensed region only when the rigid monolayer was applied. These results
      indicate that the rigidity of the matrix monolayer is a critical aspect of the
      precise manipulation of molecular machines at interfaces. Consequently, this
      study demonstrates that including a molecular machine into a rigid lipid matrix
      is a promising means for the preparation of a novel nanoassembly with dynamic
      functionalities variable depending on a mechanical stimulus.

PMID- 24569594
TI  - Regulation of MKL1 via actin cytoskeleton dynamics drives adipocyte
      differentiation.
AB  - Cellular differentiation is regulated through activation and repression of
      defined transcription factors. A hallmark of differentiation is a pronounced
      change in cell shape, which is determined by dynamics of the actin cytoskeleton.
      Here we show that regulation of the transcriptional coactivator MKL1
      (megakaryoblastic leukemia 1) by actin cytoskeleton dynamics drives adipocyte
      differentiation mediated by peroxisome proliferator-activated receptor gamma
      (PPARgamma), a master transcriptional regulator of adipogenesis. Induction of
      adipocyte differentiation results in disruption of actin stress fibres through
      downregulation of RhoA-ROCK signalling. The consequent rapid increase in
      monomeric G-actin leads to the interaction of G-actin with MKL1, which prevents
      nuclear translocation of MKL1 and allows expression of PPARgamma followed by
      adipogenic differentiation. Moreover, we found that MKL1 and PPARgamma act in a
      mutually antagonistic manner in the adipocytic differentiation programme. Our
      findings thus provide new mechanistic insight into the relation between the
      dynamics of cell shape and transcriptional regulation during cellular
      differentiation. 

PMID- 24569592
TI  - Regulation of hepatocyte growth factor expression by NF-kappaB and PPARgamma in
      adipose tissue.
AB  - Hepatocyte growth factor (HGF) is expressed as an angiogenic factor in adipose
      tissue. However, the molecular mechanism of Hgf expression remains largely
      unknown in the tissue. We addressed the issue by studying Hgf expression in
      adipocytes and macrophages. Hgf was expressed more in the stromal-vascular
      fraction than the adipocyte fraction. The expression was fivefold more in
      macrophages than the stromal-vascular faction and was reduced by 50% after
      macrophage deletion in adipose tissue. The expression was reduced by
      differentiation in adipocytes and by tumor necrosis factor-alpha or
      lipopolysaccharide treatment in macrophages. The expression was suppressed by
      nuclear factor (NF)-kappaB in C57BL/6 mice with NF-kappaB p65 overexpression
      under the aP2 gene promoter (aP2-p65 mice) but enhanced by inactivation of NF
      kappaB p65 in mouse embryonic fibroblasts. The Hgf gene promoter was suppressed
      by p65 overexpression, which blocked peroxisome proliferator-activated receptor
      gamma (PPARgamma) interaction with RNA polymerase II. The p65 activity was
      abolished by knockdown of histone deacetylase 3. Hgf expression was upregulated
      by hypoxia in vitro and in vivo. Compared with vascular endothelial growth factor
      (Vegf), which was predominately expressed in mature adipocytes, Hgf was mainly
      expressed in nonadipocytes, suggesting that Hgf and Vegf may have different cell
      sources in adipose tissue. In mechanism, Hgf expression is inhibited by NF-kappaB
      through suppression of PPARgamma function in the Hgf gene promoter. Both Hgf and
      Vegf are induced by hypoxia. The study provides a molecular mechanism for the
      difference of inflammation and hypoxia in the regulation of angiogenic factors.

PMID- 24569596
TI  - Feasibility and short-term outcomes of percutaneous transcatheter pulmonary valve
      replacement in small (<30 kg) children with dysfunctional right ventricular
      outflow tract conduits.
AB  - BACKGROUND: In 2010, the Melody transcatheter pulmonary valve (TPV) received Food
      and Drug Administration approval for treatment of dysfunctional right ventricular
      outflow tract conduits in patients >=30 kg. Limited data are available regarding
      use of this device in smaller patients. METHODS AND RESULTS: We evaluated
      technical and short-term clinical outcomes of 25 patients <30 kg (10 patients <20
      kg) who underwent TPV replacement for treatment of conduit dysfunction at 3
      centers. Median age and weight were 8.0 years (3.4-14.4) and 21.4 kg (13.8-29.0).
      The median conduit diameter at the time of surgical implant was 17 mm (12-23).
      Two patients did not undergo TPV implant (risk of coronary compression in 1;
      inability to advance the delivery sheath beyond the common femoral vein in 1).
      After successful TPV implant, the peak conduit gradient fell from 29+/-16 to 9+/
      6 mm Hg (P<0.001), and all but 2 patients had no/trivial regurgitation (down from
      moderate or severe preimplant in 20). TPV implant was via the femoral vein in 17
      patients, the right internal jugular vein in 4, and the left subclavian vein in 2
      patients. At a median follow-up of 16 months, 1 patient underwent conduit
      replacement for recurrent conduit stenosis, 2 developed stent fracture requiring
      a second TPV, and 2 developed bacterial endocarditis treated with antibiotics, 1
      of whom then underwent conduit replacement. The average Melody valve mean Doppler
      gradient and conduit regurgitation were unchanged from early postimplant.
      CONCLUSIONS: Percutaneous TPV replacement can be performed in small children with
      good procedural and early hemodynamic results in the majority of patients.

PMID- 24569597
TI  - Prognostic implications of pulmonary hypertension in patients with severe aortic
      stenosis undergoing transcatheter aortic valve implantation: study from the
      FRANCE 2 Registry.
AB  - BACKGROUND: Pulmonary hypertension (PH) is associated with poor prognosis in
      patients with severe aortic stenosis. The aim of this multicenter study was to
      describe clinical outcome after transcatheter aortic valve implantation. METHODS
      AND RESULTS: The FRANCE 2 Registry included all patients undergoing transcatheter
      aortic valve implantation in France in 2010 and 2011. Patients were divided into
      3 groups depending on systolic pulmonary artery pressure (sPAP) estimated in
      transthoracic echocardiography: group I, sPAP <40 mm Hg (no PH); group II, sPAP
      40 to 59 mm Hg (mild-to-moderate PH); and group III, sPAP >=60 mm Hg (severe PH).
      Patients were followed up for 1 year. A total of 2435 patients whose pre
      transcatheter aortic valve implantation sPAP was reported were included. A total
      of 845 were in group I (34.7%), 1112 in group II (45.7%), and 478 in group III
      (19.6%). Procedural success, early complications, and 30-day mortality were
      statistically similar across sPAP groups. One-year mortality was higher in groups
      II and III (group I, 22%; group II, 28%; and group III, 28%; P=0.032). Mild-to
      moderate and severe PH were identified as an independent factor of all-cause
      mortality. The major adverse cardiovascular event rates did not differ according
      to sPAP. New York Health Association functional class improved significantly in
      all groups. CONCLUSIONS: PH (sPAP >=40 mm Hg) in patients with aortic stenosis
      undergoing transcatheter aortic valve implantation was associated with increased
      1-year mortality especially when severe (sPAP >=60 mm Hg) but not with increased
      30-day mortality, and functional status was significantly improved regardless of
      PAP level.

PMID- 24569598
TI  - Risk of acute kidney injury after percutaneous coronary interventions using
      radial versus femoral vascular access: insights from the Blue Cross Blue Shield
      of Michigan Cardiovascular Consortium.
AB  - BACKGROUND: Transradial percutaneous coronary intervention (PCI [TRI]) does not
      involve catheter manipulation in the descending aorta, whereas transfemoral PCI
      (TFI) does. Therefore, the risk of acute kidney injury (AKI) after PCI might be
      influenced by vascular access site. We compared risks of AKI and nephropathy
      requiring dialysis (NRD) among patients treated with TRI and TFI. METHODS AND
      RESULTS: We included patients across 47 hospitals in Michigan. Primary end point
      was AKI (serum creatinine increase >=0.5 mg/dL). Secondary end points were NRD
      and postprocedural bleeding. Odds ratios (OR) for study end points were
      calculated for the entire and propensity-matched population, reported as crude,
      and values adjusted for preprocedural calculated AKI risk. Between 2010 and 2012,
      a total of 82 225 PCI procedures were performed, of which 8915 were TRI. After
      adjustment, TRI was associated with a reduction in AKI (OR, 0.76, 95% confidence
      intervals [0.62-0.92]) and bleeding with a trend toward lower NRD risk. The
      propensity-matched population consisted of 8857 procedures per group. In this
      population, TRI was associated with lower adjusted odds of AKI (OR, 0.74; 95%
      confidence intervals [0.58-0.96]), and bleeding (OR, 0.47; 95% confidence
      intervals [0.36-0.63]), but no difference in NRD was observed. Although
      postprocedural bleeding was independently associated with AKI (OR, 2.86; 95%
      confidence intervals [1.75-4.66]) in the propensity-matched population, the lower
      odds of AKI was not mediated by a reduction in bleeding with TRI. Sensitivity
      analysis demonstrated that the observed association between access site and AKI
      could potentially be explained by a moderately strong unknown confounder.
      CONCLUSIONS: The risk of AKI was significantly lower after TRI compared with TFI.
      This finding needs to be evaluated in randomized controlled trials.

PMID- 24569600
TI  - Indian medicine, coming soon to an island near you.

PMID- 24569599
TI  - Quantifying charge carrier concentration in ZnO thin films by Scanning Kelvin
      Probe Microscopy.
AB  - In the last years there has been a renewed interest for zinc oxide semiconductor,
      mainly triggered by its prospects in optoelectronic applications. In particular,
      zinc oxide thin films are being widely used for photovoltaic applications, in
      which the determination of the electrical conductivity is of great importance.
      Being an intrinsically doped material, the quantification of its doping
      concentration has always been challenging. Here we show how to probe the charge
      carrier density of zinc oxide thin films by Scanning Kelvin Probe Microscopy, a
      technique that allows measuring the contact potential difference between the tip
      and the sample surface with high spatial resolution. A simple electronic energy
      model is used for correlating the contact potential difference with the doping
      concentration in the material. Limitations of this technique are discussed in
      details and some experimental solutions are proposed. Two-dimensional doping
      concentration images acquired on radio frequency-sputtered intrinsic zinc oxide
      thin films with different thickness and deposited under different conditions are
      reported. We show that results inferred with this technique are in accordance
      with carrier concentration expected for zinc oxide thin films deposited under
      different conditions and obtained from resistivity and mobility measurements. 

PMID- 24569601
TI  - Influence of stress in GaN crystals grown by HVPE on MOCVD-GaN/6H-SiC substrate.
AB  - GaN crystals without cracks were successfully grown on a MOCVD-GaN/6H-SiC (MGS)
      substrate with a low V/III ratio of 20 at initial growth. With a high V/III ratio
      of 80 at initial growth, opaque GaN polycrystals were obtained. The structural
      analysis and optical characterization reveal that stress has a great influence on
      the growth of the epitaxial films. An atomic level model is used to explain these
      phenomena during crystal growth. It is found that atomic mobility is retarded by
      compressive stress and enhanced by tensile stress. 

PMID- 24569604
TI  - Clinical utility gene card for: Williams-Beuren Syndrome [7q11.23].

PMID- 24569603
TI  - Clinical utility gene card for: Transient Neonatal Diabetes Mellitus, 6q24
      related.

PMID- 24569605
TI  - Unexpected high intrafamilial phenotypic variability observed in
      hypophosphatasia.
AB  - Hypophosphatasia (HPP) is a clinically heterogeneous rare, inherited disorder of
      bone and mineral metabolism with extensive allelic heterogeneity in the ALPL
      gene. In this report, we present a family with heterozygous parents (maternal
      p.(Glu191Lys), paternal p.(Gly334Asp) mutations in the ALPL gene) and four
      children (one genotypically normal, one heterozygous carrier and two compound
      heterozygous) showing an unexpected high phenotypic variability. One of the
      compound heterozygous showed clinical symptoms of the mild childhood form mainly
      affecting the teeth. The other one was more seriously affected with severe
      failure to thrive, delayed motor development, need for oxygen supply and profound
      mineralization deficit compatible with an infantile form of HPP. Functional in
      vitro studies identified p.(Glu191Lys) as mild (68%, no dominant-negative effect)
      and p.(Gly334Asp) as severely affected allele (1.2%, dominant-negative effect).
      In vitro simulation of the children's genetic status showed a residual AP
      activity of 29%, while the biochemical AP activity in the serum was comparably
      reduced in both children (22 and 36 U/l). This family report indicates that
      mapping ALPL mutations within the gene does not necessarily help to predict the
      clinical severity of the phenotype. Therefore, results of prenatal diagnostics
      have to be interpreted with caution and prenatal genetic diagnosis and counseling
      for HPP should be provided within an experienced multidisciplinary team. Research
      about other confounding factors is urgently needed. 

PMID- 24569606
TI  - A defect in the CLIP1 gene (CLIP-170) can cause autosomal recessive intellectual
      disability.
AB  - In the context of a comprehensive research project, investigating novel autosomal
      recessive intellectual disability (ARID) genes, linkage analysis based on
      autozygosity mapping helped identify an intellectual disability locus on
      Chr.12q24, in an Iranian family (LOD score = 3.7). Next-generation sequencing
      (NGS) following exon enrichment in this novel interval, detected a nonsense
      mutation (p.Q1010*) in the CLIP1 gene. CLIP1 encodes a member of microtubule (MT)
      plus-end tracking proteins, which specifically associates with the ends of
      growing MTs. These proteins regulate MT dynamic behavior and are important for MT
      mediated transport over the length of axons and dendrites. As such, CLIP1 may
      have a role in neuronal development. We studied lymphoblastoid and skin
      fibroblast cell lines established from healthy and affected patients. RT-PCR and
      western blot analyses showed the absence of CLIP1 transcript and protein in
      lymphoblastoid cells derived from affected patients. Furthermore,
      immunofluorescence analyses showed MT plus-end staining only in fibroblasts
      containing the wild-type (and not the mutant) CLIP1 protein. Collectively, our
      data suggest that defects in CLIP1 may lead to ARID.

PMID- 24569608
TI  - Clinical utility gene card for: Phosphomannose isomerase deficiency.

PMID- 24569607
TI  - Cell therapy using retinal progenitor cells shows therapeutic effect in a
      chemically-induced rotenone mouse model of Leber hereditary optic neuropathy.
AB  - Primary mitochondrial disorders occur at a prevalence of one in 10 000; ~50% of
      these demonstrate ocular pathology. Leber hereditary optic neuropathy (LHON) is
      the most common primary mitochondrial disorder. LHON results from retinal
      ganglion cell pathology, which leads to optic nerve degeneration and blindness.
      Over 95% of cases result from one of the three common mutations in mitochondrial
      genes MTND1, MTND4 and MTND6, which encode elements of the complex I respiratory
      chain. Various therapies for LHON are in development, for example, intravitreal
      injection of adeno-associated virus carrying either the yeast NDI1 gene or a
      specific subunit of mammalian Complex I have shown visual improvement in animal
      models. Given the course of LHON, it is likely that in many cases prompt
      administration may be necessary before widespread cell death. An alternative
      approach for therapy may be the use of stem cells to protect visual function;
      this has been evaluated by us in a rotenone-induced model of LHON. Freshly
      dissected embryonic retinal cells do not integrate into the ganglion cell layer
      (GCL), unlike similarly obtained photoreceptor precursors. However, cultured
      retinal progenitor cells can integrate in close proximity to the GCL, and act to
      preserve retinal function as assessed by manganese-enhanced magnetic resonance
      imaging, optokinetic responses and ganglion cell counts. Cell therapies for LHON
      therefore represent a promising therapeutic approach, and may be of particular
      utility in treating more advanced disease. 

PMID- 24569610
TI  - Dipolar polarization and piezoelectricity of a hexagonal boron nitride sheet
      decorated with hydrogen and fluorine.
AB  - In contrast to graphene, a hexagonal boron nitride (h-BN) monolayer is
      piezoelectric because it is non-centrosymmetric. However, h-BN shows neither in
      plane nor out-of-plane dipole moments due to its three-fold symmetry on the plane
      and the fact that it is completely flat. Here, we show that the controlled
      adsorption of hydrogen and/or fluorine atoms on both sides of a pristine h-BN
      sheet induces flatness distortion in a chair form and an out-of plane dipole
      moment. In contrast, a boat form has no out-of-plane dipole moment due to the
      alternating boron and nitrogen positions normal to the plane. Consequently, the
      chair form of surface-modified h-BN shows both in-plane and out-of-plane
      piezoelectric responses; while pristine h-BN and the boat form of decorated h-BN
      have only in-plane piezoelectric responses. These in-plane and out-of-plane
      piezoelectric responses of the modified h-BN are comparable to those in known
      three-dimensional piezoelectric materials. Such an engineered piezoelectric two
      dimensional boron nitride monolayer can be a candidate material for various nano
      electromechanical applications. 

PMID- 24569609
TI  - Coffin-Siris Syndrome with obesity, macrocephaly, hepatomegaly and
      hyperinsulinism caused by a mutation in the ARID1B gene.
AB  - Coffin-Siris Syndrome (CSS, MIM 135900) is a rare genetic disorder, and mutations
      in ARID1B were recently shown to cause CSS. In this study, we report a novel
      ARID1B mutation identified by whole-exome sequencing in a patient with clinical
      features of CSS. We identified a novel heterozygous frameshift mutation
      c.1584delG in exon 2 of ARID1B (NM_020732.3) predicting a premature stop codon
      p.(Leu528Phefs*65). Sanger sequencing confirmed the c.1584delG mutation as a de
      novo in the proband and that it was not present either in her parents, half
      sister or half-brother. Clinically, the patient presented with extreme obesity,
      macrocephaly, hepatomegaly, hyperinsulinism and polycystic ovarian syndrome
      (PCOS), which have previously not been described in CSS patients. We suggest that
      obesity, macrocephaly, hepatomegaly and/or PCOS may be added to the list of
      clinical features of ARID1B mutations, but further clinical reports are required
      to make a definite conclusion. 

PMID- 24569612
TI  - Porcine circovirus: a historical perspective.
AB  - Porcine circoviruses (PCVs) belong to the genus Circovirus and the family
      Circoviridae, and they are the smallest known viruses that replicate autonomously
      in mammalian cells. They are nonenveloped, and they have characteristic single
      stranded, negative-sense, circular DNA. Two types of divergent PCVs are
      recognized: PCV1 and PCV2. About 20 years ago, PCV2 began to emerge as a major
      pathogen of swine around the world, leading to burgeoning knowledge about the
      virus and porcine circovirus-associated diseases. However, much of the history of
      its discovery, including the controversy related to its importance, is not
      recorded. This review examines current issues related to the biology of PCV2 in
      the context of the original studies related to determining its causal association
      with disease and to the evolving understanding of the complex pathogenesis of
      PCV2 infections. 

PMID- 24569613
TI  - Nonculture molecular techniques for diagnosis of bacterial disease in animals: a
      diagnostic laboratory perspective.
AB  - The past decade has seen remarkable technical advances in infectious disease
      diagnosis, and the pace of innovation is likely to continue. Many of these
      techniques are well suited to pathogen identification directly from pathologic or
      clinical samples, which is the focus of this review. Polymerase chain reaction
      (PCR) and gene sequencing are now routinely performed on frozen or fixed tissues
      for diagnosis of bacterial infections of animals. These assays are most useful
      for pathogens that are difficult to culture or identify phenotypically, when
      propagation poses a biosafety hazard, or when suitable fresh tissue is not
      available. Multiplex PCR assays, DNA microarrays, in situ hybridization, massive
      parallel DNA sequencing, microbiome profiling, molecular typing of pathogens,
      identification of antimicrobial resistance genes, and mass spectrometry are
      additional emerging technologies for the diagnosis of bacterial infections from
      pathologic and clinical samples in animals. These technical advances come,
      however, with 2 caveats. First, in the age of molecular diagnosis, quality
      control has become more important than ever to identify and control for the
      presence of inhibitors, cross-contamination, inadequate templates from diagnostic
      specimens, and other causes of erroneous microbial identifications. Second, the
      attraction of these technologic advances can obscure the reality that medical
      diagnoses cannot be made on the basis of molecular testing alone but instead
      through integrated consideration of clinical, pathologic, and laboratory
      findings. Proper validation of the method is required. It is critical that
      veterinary diagnosticians understand not only the value but also the limitations
      of these technical advances for routine diagnosis of infectious disease. 

PMID- 24569614
TI  - Gammaherpesviruses and pulmonary fibrosis: evidence from humans, horses, and
      rodents.
AB  - Progressive lung fibrosis in humans, typified by idiopathic pulmonary fibrosis
      (IPF), is a serious cause of morbidity and mortality in people. Similar diseases
      have been described in dogs, cats, and horses. The cause and pathogenesis of such
      diseases in all species is poorly understood. There is growing evidence in human
      medicine that IPF is a manifestation of abnormal wound repair in response to
      epithelial injury. Because viruses can contribute to epithelial injury, there is
      increasing interest in a possible role of viruses, particularly
      gammaherpesviruses, in the pathogenesis of pulmonary fibrosis. This review
      provides background information on progressive fibrosing lung disease in human
      and veterinary medicine and summarizes the evidence for an association between
      gammaherpesvirus infection and pulmonary fibrosis, especially Epstein-Barr virus
      in human pulmonary fibrosis, and equine herpesvirus 5 in equine multinodular
      pulmonary fibrosis. Data derived from experimental lung infection in mice with
      the gammaherpesvirus murine herpesvirus are presented, emphasizing the host and
      viral factors that may contribute to lung fibrosis. The experimental data are
      considered in the context of the pathogenesis of naturally occurring pulmonary
      fibrosis in humans and horses. 

PMID- 24569615
TI  - The worm turns: trematodes steering the course of co-infections.
AB  - A reductionist approach to the study of infection does not lend itself to an
      appraisal of the interactions that occur between 2 or more organisms that infect
      a host simultaneously. In reality, hosts are subject to multiple simultaneous
      influences from multiple pathogens along the spectrum from symbiotic microflora
      to virulent pathogen. In this review, we draw from our own work on Fasciola
      hepatica and that of others studying helminth co-infection to give examples of
      how such interactions can influence not only the outcome of infection but also
      its diagnosis and control. The new tools of systems biology, including both the
      "omics" approaches and mathematical biology, have significant promise in
      unraveling the as yet largely unexplored complexities of co-infection. 

PMID- 24569616
TI  - Feline infectious peritonitis: still an enigma?
AB  - Feline infectious peritonitis (FIP) is one of the most important fatal infectious
      diseases of cats, the pathogenesis of which has not yet been fully revealed. The
      present review focuses on the biology of feline coronavirus (FCoV) infection and
      the pathogenesis and pathological features of FIP. Recent studies have revealed
      functions of many viral proteins, differing receptor specificity for type I and
      type II FCoV, and genomic differences between feline enteric coronaviruses
      (FECVs) and FIP viruses (FIPVs). FECV and FIP also exhibit functional
      differences, since FECVs replicate mainly in intestinal epithelium and are shed
      in feces, and FIPVs replicate efficiently in monocytes and induce systemic
      disease. Thus, key events in the pathogenesis of FIP are systemic infection with
      FIPV, effective and sustainable viral replication in monocytes, and activation of
      infected monocytes. The host's genetics and immune system also play important
      roles. It is the activation of monocytes and macrophages that directly leads to
      the pathologic features of FIP, including vasculitis, body cavity effusions, and
      fibrinous and granulomatous inflammatory lesions. Advances have been made in the
      clinical diagnosis of FIP, based on the clinical pathologic findings, serologic
      testing, and detection of virus using molecular (polymerase chain reaction) or
      antibody-based methods. Nevertheless, the clinical diagnosis remains challenging
      in particular in the dry form of FIP, which is partly due to the incomplete
      understanding of infection biology and pathogenesis in FIP. So, while much
      progress has been made, many aspects of FIP pathogenesis still remain an enigma. 

PMID- 24569617
TI  - Career advancement opportunities and the ACVP/STP Coalition.

PMID- 24569618
TI  - Diary of hot flashes reported upon occurrence: results of a randomized double
      blind study of raloxifene, placebo, and paroxetine.
AB  - OBJECTIVE: This trial examined diaries of hot flash events reported upon
      occurrence to assess the test/retest reliability of the diaries and their ability
      to measure treatment effects on hot flash frequency and severity. METHODS: Forty
      two postmenopausal women (aged >=40 y; 5-50 hot flashes/wk) were randomized
      (3:3:1) to placebo, raloxifene 60 mg, or paroxetine 20 mg daily for 12 weeks.
      Diaries of hot flash frequency and severity were evaluated at 1-week intervals
      (twice before study treatment and thrice during study treatment). RESULTS: Forty
      one women were evaluated. Baseline characteristics were similar between groups
      (eg, mean, 29.8 hot flashes/wk). Concordance correlation coefficients between
      screening (week -2) and baseline (week -1) measures of hot flash frequency and
      severity were 0.73 and 0.71, respectively. After 12 weeks, the mean (95% CI)
      percent changes from baseline in weekly hot flash frequency were as follows:
      placebo, -37.4% (-60.9 to -14.0); raloxifene, -14.2% (-37.7 to 9.3); paroxetine, 
      49.8% (-88.6 to -11.0); the mean (95% CI) percent changes in hot flash severity
      were as follows: placebo, -39.9% (-69.1 to -10.8); raloxifene, -9.6% (-38.8 to
      19.6); paroxetine, -36.6% (-84.7 to 11.5). There were no significant differences
      in hot flash diary results between treatment groups. CONCLUSIONS: Measures of hot
      flash frequency and severity show acceptable test/retest reliability between
      screening and baseline. Reductions in vasomotor symptoms by raloxifene are
      numerically less than those seen with placebo, but no statistically significant
      treatment differences have been documented in this small study. The large effect
      of placebo and the significant reduction in vasomotor symptoms by paroxetine are
      consistent with other studies. The diary seems to be suitable for use in hot
      flash clinical trials.

PMID- 24569619
TI  - Relationship of sleep alterations with perimenopausal and postmenopausal
      symptoms.
AB  - OBJECTIVE: Sleep disturbance is an important change in menopause because it
      affects quality of life and can lead to other conditions such as depression. This
      study measured sleep alterations and explored associated physical, emotional,
      hormonal, and lifestyle factors during perimenopause and postmenopause. METHODS:
      This cross-sectional study enrolled 160 women who were classified as
      perimenopausal (n = 85) or postmenopausal (n = 75). Using diaries, we collected
      data on duration of sleep, time awake in bed, and sleep efficiency. Follicle
      stimulating hormone, 17beta-estradiol, and cortisol levels were quantified by
      radioimmunoassay, and serum anti-Mullerian hormone levels were measured using
      enzyme-linked immunosorbent assay. Correlations between sleep measurements and
      symptoms were assessed using a generalized linear model. RESULTS: The reported
      duration of sleep was similar for both groups of women (close to 6.9 h), and
      sleep efficiency was 88%. We did not find any factor that was associated with
      duration of sleep. Sleep efficiency was negatively associated with age,
      perimenopause/postmenopause status, loss of sexual interest, hot flashes, and
      depressed mood. Time awake in bed was positively associated with depressed mood
      (P < 0.000001), cigarette smoking (P < 0.000041), menopause status (P < 0.00009),
      and age (P < 0.0009). These associations remained after controlling for exercise,
      alcohol consumption, and caffeine consumption as confounding variables. Finally,
      morning salivary cortisol was reduced in postmenopausal women. CONCLUSIONS: Time
      awake in bed shows the most significant associations. Depressed mood, age, and
      menopause status are the main factors associated with sleep disturbances.

PMID- 24569620
TI  - Ovarian estradiol production and lipid metabolism in postmenopausal women.
AB  - OBJECTIVE: Menopause is defined as the permanent cessation of menses. Although
      previous studies demonstrated a slight production of androgens and estrogens by
      postmenopausal ovaries, the impact of hormone production on lipid metabolism is
      still uncertain. The aim of this study was to evaluate whether the postmenopausal
      ovary is hormonally active and whether hormone status contributes to lipid
      metabolism. METHODS: This was a prospective study of 87 women who were treated
      for gynecological diseases (29% had cervical cancer, 49% had endometrial cancer,
      7% had fibroid tumors, and 15% had cervical intraepithelial neoplasia). They were
      categorized as early postmenopausal (n = 40; mean [SD], 56.8 [3.8] y) or late
      postmenopausal (n = 47; mean [SD], 66.6 [5.7] y) women. Serum specimens were
      collected from the peripheral and ovarian veins of participants undergoing
      bilateral oophorectomy. Sex steroid hormone levels and lipid profiles were
      determined. RESULTS: Statistically significant differences in estradiol (E2) and
      testosterone were seen between the ovarian samples and the peripheral samples in
      all groups. E2 and estrone obtained from ovarian venous samples gradually
      decreased with age in postmenopausal women. There was a significant correlation
      between ovarian E2 and high-density lipoprotein cholesterol levels and the low
      density lipoprotein-to-high-density lipoprotein ratio. However, there was no
      correlation between peripheral E2 levels and any of the lipid parameters
      examined. CONCLUSIONS: Although this study investigates women with gynecological
      diseases, the postmenopausal ovary is hormonally active, and the E2 produced by
      postmenopausal ovaries may therefore contribute to the maintenance of lipid
      metabolism.

PMID- 24569622
TI  - WITHDRAWN: Regulation of plasma membrane receptors by a new autophagy-related
      BECN/Beclin family member.

PMID- 24569621
TI  - Switch patterns of osteoporosis medication and its impact on persistence among
      postmenopausal women in the U.K. General Practice Research Database.
AB  - OBJECTIVE: This study aims to describe the switch patterns of osteoporosis
      medication in postmenopausal women and to explore the impact of switching on
      persistence. METHODS: This study used a cohort of postmenopausal women who
      initiated the first treatment with osteoporosis medication between 1995 and 2008.
      Selected women had switched at least once to a different frequency or type of
      osteoporosis medication during follow-up. For each study woman, we identified the
      first therapy (initial osteoporosis medication), second therapy (medication
      received at first switch), and, where available, third therapy (medication
      received at second switch), regardless of how many times she switched during
      follow-up. Persistence was defined as the number of days from the index date to
      the end of the last prescription within each episode of use. The Kaplan-Meier
      method was used to calculate persistence rates at 6 months, 1 year, 3 years, and
      5 years. RESULTS: Of 20,638 women who switched osteoporosis treatment at least
      once in the study period, approximately 67% switched once, 21% switched twice,
      and 12% switched three times or more. Persistence rates for the second therapy
      were highest (% [95% CI], 46.6 [46.1-47.1], 35.0 [34.5-35.5], 18.8 [18.3-19.3],
      and 11.4 [10.9-11.7] at 6 mo, 1 y, 3 y, and 5 y, respectively), whereas
      persistence rates for the first therapy were lowest (% [95% CI], 34.3 [33.9
      34.8], 21.6 [21.2-21.9], 5.90 [5.68-6.13], and 1.57 [1.45-1.69], respectively).
      CONCLUSIONS: Among women who switch their initial medication, even though
      switching to the second medication improves persistence during the initial
      therapy, persistence on the second and subsequent therapies remains suboptimal.

PMID- 24569625
TI  - Hepcidin is linked to hypoferremia in patients with rheumatic valve disease.
AB  - BACKGROUND AND AIM: Hepcidin has been shown to be an acute phase reactant,
      induced by infection and inflammation. Ongoing inflammation was shown in
      rheumatic valve disease (RVD). In this study we want to investigate whether there
      is a relationship between inflammation and impaired iron metabolism and the role
      of hepcidin on serum iron levels. METHODS AND RESULTS: Fourty-six patients with
      RVD and 34 healthy individuals were included in the study. Serum hepcidin, high
      sensitive C-reactive protein (hs-CRP), hemoglobin, hematocrit, iron, iron-binding
      capacity, ferritin levels were measured. Serum hepcidin levels were significantly
      increased in patients with RVD than in control group (316 +/- 121 ng/mL vs 435 +/
      126 ng/mL; P < .001). Serum hs-CRP levels were no significantly higher in the
      patient group in than in the control group (3.9 +/- 3.6 mg/L vs 3.5 +/- 3.7 mg/L;
      P = .521). CONCLUSION: Hepcidin levels are decreased independently from hs-CRP
      levels as a compensatory mechanism to increase the iron absorption in response to
      decreased serum iron levels in patients with RVD.

PMID- 24569623
TI  - Examining the association of lung cancer and highly correlated fibre size
      specific asbestos exposures with a hierarchical Bayesian model.
AB  - BACKGROUND: Asbestos is a known carcinogen. However, little is known about the
      differential effects of size-specific asbestos fibres. Previous research has
      examined the relationship with lung cancer of each fibre group in the absence of
      others. Attempts to model all fibre groups within a single regression model have
      failed due to high correlations across fibre size groups. METHODS: We compare
      results from frequentist models for individual fibre size groups, and a
      hierarchical Bayesian model that included all fibre groups to estimate the
      relationship of size-specific asbestos fibre groups to lung cancer mortality. The
      hierarchical model assumes partial exchangeability of the effects of size
      specific asbestos fibre groups to lung cancer, and is capable of handling the
      strong correlation of the exposure data. RESULTS: When fibre groups are modelled
      independently with a frequentist model, there appears to be an increase in the
      dose-response with increasing fibre size. However, when subject to a hierarchical
      structure, this trend vanishes, and the effects of distinct fibre groups appear
      largely similar. CONCLUSIONS: This is the first occasion where distinct asbestos
      fibre groups have been assessed in a single regression model; however, even the
      use of a hierarchical modelling structure does not appear to overcome all the
      statistical fluctuations arising from the high correlations across fibre groups.
      We believe these results should be compared with other occupational cohorts with
      similar fibre group information. Finally, results for the smallest fibre group
      may be suggestive of a carcinogenic potential for nanofibres.

PMID- 24569626
TI  - Thrombophilic mutations as risk factor for retinal vein occlusion: a case-control
      study.
AB  - BACKGROUND: Retinal vein occlusion (RVO) is the second most common retinal vein
      disease and an important cause of blindness and visual morbidity. Many conditions
      are associated with RVO but the real role of the thrombophilic mutations is still
      unclear. AIM: To evaluate the potential role of thrombophilic mutations in RVO.
      METHODS: We have evaluated 113 patients with RVO and compared with 104 volunteer
      controls. The controls were all healthy blood donors without previous venous
      thromboembolism episode or arterial thromboembolism episode. All patients were
      tested for 5 gene variants (here all named as mutations): factor V (FV) Leiden
      (G1691A), factor II (FII; G20210A), 5,1-methylenetetra-hydrofolate reductase
      (MTHFR; C677T), plasminogen activator inhibitor 1 (PAI-1; 4G/5G), and angiotensin
      converting enzyme (ACE; Del/Ins). Statistical analysis were performed by the 2
      tailed chi-square test. RESULTS: Statistical test showed that TT homozygous
      patients of the MTHFR C677T mutation (P = .017) and heterozygous GA patients of
      the FII G20210A mutation (P = .018) were significantly higher than that in
      controls. For FV Leiden, even if the values were higher in patients than in
      controls, P value was not statistically significant. Conversely, for the ACE
      (Ins/Del) and PAI-1 (4G/5G) mutations, no difference was observed among genotypes
      of patients with RVO and control participants. CONCLUSIONS: In our study, the FII
      G20210A and the MTHFR C677T mutations resulted significantly higher in patients
      than in controls; in contrast, thrombophilic mutation of FV, ACE, and PAI-1 genes
      was not statistically correlated with RVO. In spite of having found an
      association between some thrombophilic mutations and RVO, more studies with a
      major number of patients are necessary to determine the final role of these gene
      variants.

PMID- 24569627
TI  - Endothelial dysfunction in patients with coronary artery disease: insights from a
      flow-mediated dilation study.
AB  - BACKGROUND: The use of flow-mediated dilation (FMD) as a surrogate indicator for
      the extent of coronary artery disease (CAD) remains largely unknown. We assessed
      FMD at the brachial artery in 89 consecutive patients undergoing coronary
      angiography. METHODS AND RESULTS: Patients were classified in groups 0 to 3
      according to the number of diseased vessels and the SYNTAX score was calculated.
      The FMD decreased significantly from groups 0 to 3 (P < .001). There was a
      significant linear relation between SYNTAX score and FMD (corrected r (2) = .64,
      P < .001). In multivariate analysis, a reduced FMD was the only significant
      independent predictor of the presence of CAD (odds ratio [OR] 1.78, P = .032) and
      of CAD severity (OR 1.85, P = .005). CONCLUSION: This study confirms that FMD is
      reduced in patients with CAD and that such reduction in FMD is related to the
      extent of the disease. Therefore, FMD at the brachial artery is likely to
      represent a reliable indicator of CAD burden.

PMID- 24569629
TI  - Measurements of the in vitro anti-mycobacterial activity of ivermectin are method
      dependent.

PMID- 24569630
TI  - Novel non-neuroleptic phenothiazines inhibit Mycobacterium tuberculosis
      replication.
AB  - OBJECTIVES: Phenothiazines are a commercially available class of psychotropic
      drugs known to show antituberculosis activity. At clinically relevant
      bactericidal doses, however, the psychotropic drugs produce undesirable side
      effects in addition to their neuroleptic properties. This study aimed to evaluate
      rationally designed novel phenothiazines as antimycobacterial drug candidates.
      METHODS: Remodelling of psychotropic drugs by substitution of characteristic N
      alkylamine side chains, important for CNS activity, with N-alkylsulphonates gave
      novel drug candidates, which were then tested for post-synaptic receptor binding
      affinity in a radioligand displacement assay. The bactericidal activities were
      screened using green fluorescent protein (GFP) microplate assays, and the
      efficacy of intracellular bacillus killing was evaluated by cfu enumeration.
      RESULTS: Of the four selected phenothiazine derivatives (PTZ3, PTZ4, PTZ31 and
      PTZ32) tested, PTZ31 displayed marginal serotonergic activity. The remaining
      three derivatives did not exhibit dopamine or serotonin receptor binding
      activity. In vitro results showed significant growth inhibition of virulent
      Mycobacterium tuberculosis with MICs of 12.5-25 mg/L. None of the phenothiazine
      derivatives displayed cytotoxicity in infected primary bone marrow-derived
      macrophages. Moreover, the phenothiazines showed significant antimycobacterial
      activity of between 40% and 60% against intracellular (ex vivo) M. tuberculosis.
      CONCLUSIONS: We demonstrate that structural modification of the phenothiazine
      core is possible in a manner that does not affect the ability of the
      phenothiazine derivatives to inhibit M. tuberculosis, but that abolishes
      undesirable dopamine and serotonin receptor binding.

PMID- 24569628
TI  - Delayed bactericidal response of Mycobacterium tuberculosis to bedaquiline
      involves remodelling of bacterial metabolism.
AB  - Bedaquiline (BDQ), an ATP synthase inhibitor, is the first drug to be approved
      for treatment of multidrug-resistant tuberculosis in decades. Though BDQ has
      shown excellent efficacy in clinical trials, its early bactericidal activity
      during the first week of chemotherapy is minimal. Here, using microfluidic
      devices and time-lapse microscopy of Mycobacterium tuberculosis, we confirm the
      absence of significant bacteriolytic activity during the first 3-4 days of
      exposure to BDQ. BDQ-induced inhibition of ATP synthesis leads to bacteriostasis
      within hours after drug addition. Transcriptional and proteomic analyses reveal
      that M. tuberculosis responds to BDQ by induction of the dormancy regulon and
      activation of ATP-generating pathways, thereby maintaining bacterial viability
      during initial drug exposure. BDQ-induced bacterial killing is significantly
      enhanced when the mycobacteria are grown on non-fermentable energy sources such
      as lipids (impeding ATP synthesis via glycolysis). Our results show that BDQ
      exposure triggers a metabolic remodelling in mycobacteria, thereby enabling
      transient bacterial survival. 

PMID- 24569631
TI  - Detection of a new mecC allotype, mecC2, in methicillin-resistant Staphylococcus
      saprophyticus.

PMID- 24569632
TI  - Quantitative decoding of interactions in tunable nanomagnet arrays using first
      order reversal curves.
AB  - To develop a full understanding of interactions in nanomagnet arrays is a
      persistent challenge, critically impacting their technological acceptance. This
      paper reports the experimental, numerical and analytical investigation of
      interactions in arrays of Co nanoellipses using the first-order reversal curve
      (FORC) technique. A mean-field analysis has revealed the physical mechanisms
      giving rise to all of the observed features: a shift of the non-interacting FORC
      ridge at the low-HC end off the local coercivity HC axis; a stretch of the FORC
      ridge at the high-HC end without shifting it off the HC axis; and a formation of
      a tilted edge connected to the ridge at the low-HC end. Changing from flat to
      Gaussian coercivity distribution produces a negative feature, bends the ridge,
      and broadens the edge. Finally, nearest neighbor interactions segment the FORC
      ridge. These results demonstrate that the FORC approach provides a comprehensive
      framework to qualitatively and quantitatively decode interactions in nanomagnet
      arrays. 

PMID- 24569634
TI  - Use of renin-angiotensin system blockers in acute coronary syndromes: findings
      from Get With the Guidelines-Coronary Artery Disease Program.
AB  - BACKGROUND: Angiotensin-converting enzyme inhibitors (ACEI) or angiotensin
      receptor blockers (ARB) initiated after myocardial infarction (MI) reduce
      mortality and are American College of Cardiology/American Heart Association
      guideline recommended. Yet the extent to which ACEI/ARB therapy is applied in
      patients with acute coronary syndrome at hospital discharge is unclear. METHODS
      AND RESULTS: We performed an observational analysis of 80 241 patients admitted
      with an acute coronary syndrome and discharged home from 311 U.S. hospitals
      participating in the Get With the Guidelines-Coronary Artery Disease Program from
      January 2005 to December 2009. Among the 60,847 patients with an American College
      of Cardiology/American Heart Association class I indication (left ventricular
      dysfunction or medical history of heart failure, hypertension, diabetes mellitus,
      or chronic kidney disease), 49,682 (81.7%) received ACEI/ARB with an increase in
      the rate of treatment over the study period (76.7%-84.6%; adjusted odds ratio,
      1.17; 95% confidence interval, 1.10-1.24; P<0.001, per calendar year). In
      hospital coronary artery bypass grafting and renal insufficiency were
      independently associated with lower use (adjusted odds ratio, 0.55; 95%
      confidence interval, 0.48-0.63 and adjusted odds ratio, 0.58; 95% confidence
      interval, 0.52-0.64, respectively). CONCLUSIONS: Results from this large U.S.
      national registry suggest that 1 in 5 eligible patients hospitalized for acute
      coronary syndrome failed to receive American College of Cardiology/American Heart
      Association class I guideline-recommended ACEI/ARB therapy, and the use varies by
      patient factors. In particular, the low likelihood of ACEI/ARB after coronary
      artery bypass grafting surgery or in patients with renal insufficiency raises
      concern. These findings highlight an unmet need in this population and provide an
      incentive for additional quality improvement efforts.

PMID- 24569633
TI  - A critical re-assessment of DNA repair gene promoter methylation in non-small
      cell lung carcinoma.
AB  - DNA repair genes that have been inactivated by promoter methylation offer
      potential therapeutic targets either by targeting the specific repair deficiency,
      or by synthetic lethal approaches. This study evaluated promoter methylation
      status for eight selected DNA repair genes (ATM, BRCA1, ERCC1, MGMT, MLH1, NEIL1,
      RAD23B and XPC) in 56 non-small cell lung cancer (NSCLC) tumours and 11 lung cell
      lines using the methylation-sensitive high resolution melting (MS-HRM)
      methodology. Frequent methylation in NEIL1 (42%) and infrequent methylation in
      ERCC1 (2%) and RAD23B (2%) are reported for the first time in NSCLC. MGMT
      methylation was detected in 13% of the NSCLCs. Contrary to previous studies,
      methylation was not detected in ATM, BRCA1, MLH1 and XPC. Data from The Cancer
      Genome Atlas (TCGA) was consistent with these findings. The study emphasises the
      importance of using appropriate methodology for accurate assessment of promoter
      methylation. 

PMID- 24569635
TI  - Quantitative trait loci from the host genetic background modulate the durability
      of a resistance gene: a rational basis for sustainable resistance breeding in
      plants.
AB  - The combination of major resistance genes with quantitative resistance factors is
      hypothesized as a promising breeding strategy to preserve the durability of
      resistant cultivar, as recently observed in different pathosystems. Using the
      pepper (Capsicum annuum)/Potato virus Y (PVY, genus Potyvirus) pathosystem, we
      aimed at identifying plant genetic factors directly affecting the frequency of
      virus adaptation to the major resistance gene pvr2(3) and at comparing them with
      genetic factors affecting quantitative resistance. The resistance breakdown
      frequency was a highly heritable trait (h(2)=0.87). Four loci including additive
      quantitative trait loci (QTLs) and epistatic interactions explained together 70%
      of the variance of pvr2(3) breakdown frequency. Three of the four QTLs
      controlling pvr2(3) breakdown frequency were also involved in quantitative
      resistance, strongly suggesting that QTLs controlling quantitative resistance
      have a pleiotropic effect on the durability of the major resistance gene. With
      the first mapping of QTLs directly affecting resistance durability, this study
      provides a rationale for sustainable resistance breeding. Surprisingly, a genetic
      trade-off was observed between the durability of PVY resistance controlled by
      pvr2(3) and the spectrum of the resistance against different potyviruses. This
      trade-off seemed to have been resolved by the combination of minor-effect
      durability QTLs under long-term farmer selection. 

PMID- 24569636
TI  - Mammalian viviparity: a complex niche in the evolution of genomic imprinting.
AB  - Evolution of mammalian reproductive success has witnessed a strong dependence on
      maternal resources through placental in utero development. Genomic imprinting,
      which has an active role in mammalian viviparity, also reveals a biased role for
      matrilineal DNA in its regulation. The co-existence of three matrilineal
      generations as one (mother, foetus and post-meiotic oocytes) has provided a
      maternal niche for transgenerational co-adaptive selection pressures to operate.
      In utero foetal growth has required increased maternal feeding in advance of
      foetal energetic demands; the mammary glands are primed for milk production in
      advance of birth, while the maternal hypothalamus is hormonally primed by the
      foetal placenta for nest building and post-natal care. Such biological forward
      planning resulted from maternal-foetal co-adaptation facilitated by co-expression
      of the same imprinted allele in the developing hypothalamus and placenta. This co
      expression is concurrent with the placenta interacting with the adult maternal
      hypothalamus thereby providing a transgenerational template on which selection
      pressures may operate ensuring optimal maternalism in this and the next
      generation. Invasive placentation has further required the maternal immune system
      to adapt and positively respond to the foetal allotype. Pivotal to these
      mammalian evolutionary developments, genomic imprinting emerged as a monoallelic
      gene dosage regulatory mechanism of tightly interconnected gene networks
      providing developmental genetic stability for in utero development. 

PMID- 24569638
TI  - Furore over care.data programme could jeopardise future medical research, doctors
      and charities warn.

PMID- 24569639
TI  - Exposure to environmental tobacco smoke and risk of non-Hodgkin lymphoma in
      nonsmoking men and women.
AB  - Little is known about the risk of non-Hodgkin lymphoma (NHL) in nonsmokers who
      are exposed to environmental tobacco smoke (ETS). Previous research on NHL and
      ETS has not included men or examined doses of ETS exposure during childhood. The
      Cancer Prevention Study II Nutrition Cohort collected information on smoking
      habits and exposure to ETS during childhood and adulthood. Among 61,326 never
      smoking men and women, 884 incident cases of NHL were identified between 1992 and
      2009. Multivariable-adjusted relative risks and 95% confidence intervals were
      calculated using Cox proportional hazards regression to identify associations
      between ETS and NHL risk. Compared with no exposure to ETS as a child or an
      adult, childhood and/or adult ETS exposure was not associated with NHL overall.
      There was a positive association between the number of smokers in the house as a
      child (P for trend = 0.05) and exposure to 6 or more hours per week of ETS as an
      adult (relative risk = 2.37, 95% confidence interval: 1.12, 5.04) with follicular
      lymphoma risk. Adult ETS exposure was associated with a lower risk of diffuse
      large B-cell lymphoma (relative risk = 0.68, 95% confidence interval: 0.48,
      0.97). This study suggests that adult and childhood ETS exposure may affect the
      risk of NHL, and that the associations differ by histological subtype. 

PMID- 24569637
TI  - Fine-mapping quantitative trait loci affecting murine external ear tissue
      regeneration in the LG/J by SM/J advanced intercross line.
AB  - External ear hole closure in LG/J mice represents a model of regenerative
      response. It is accompanied by the formation of a blastema-like structure and the
      re-growth of multiple tissues, including cartilage. The ability to regenerate
      tissue is heritable. An F34 advanced intercross line of mice (Wustl:LG,SM-G34)
      was generated to identify genomic loci involved in ear hole closure over a 30-day
      healing period. We mapped 19 quantitative trait loci (QTL) for ear hole closure.
      Individual gene effects are relatively small (0.08 mm), and most loci have co
      dominant effects with phenotypically intermediate heterozygotes. QTL support
      regions were limited to a median size of 2 Mb containing a median of 19 genes.
      Positional candidate genes were evaluated using differential transcript
      expression between LG/J and SM/J healing tissue, function analysis and
      bioinformatic analysis of single-nucleotide polymorphisms in and around
      positional candidate genes of interest. Analysis of the set of 34 positional
      candidate genes and those displaying expression differences revealed over
      representation of genes involved in cell cycle regulation/DNA damage, cell
      migration and adhesion, developmentally related genes and metabolism. This
      indicates that the healing phenotype in LG/J mice involves multiple physiological
      mechanisms.

PMID- 24569641
TI  - Obesity as a risk factor for sciatica: a meta-analysis.
AB  - The aim of this study was to assess the associations of overweight and obesity
      with lumbar radicular pain and sciatica using a meta-analysis. We searched the
      PubMed, Embase, Scopus, and Web of Science databases from 1966 to July 2013. We
      performed a random-effects meta-analysis and assessed publication bias. We
      included 26 (8 cross-sectional, 7 case-control, and 11 cohort) studies. Both
      overweight (pooled odds ratio (OR) = 1.23, 95% confidence interval (CI): 1.14,
      1.33; n = 19,165) and obesity (OR = 1.40, 95% CI: 1.27, 1.55; n = 19,165) were
      associated with lumbar radicular pain. The pooled odds ratio for physician
      diagnosed sciatica was 1.12 (95% CI: 1.04, 1.20; n = 109,724) for overweight and
      1.31 (95% CI: 1.07, 1.62; n = 115,661) for obesity. Overweight (OR = 1.16, 95%
      CI: 1.09, 1.24; n = 358,328) and obesity (OR = 1.38, 95% CI: 1.23, 1.54; n =
      358,328) were associated with increased risk of hospitalization for sciatica, and
      overweight/obesity was associated with increased risk of surgery for lumbar disc
      herniation (OR = 1.89, 95% CI: 1.25, 2.86; n = 73,982). Associations were similar
      for men and women and were independent of the design and quality of included
      studies. There was no evidence of publication bias. Our findings consistently
      showed that both overweight and obesity are risk factors for lumbar radicular
      pain and sciatica in men and women, with a dose-response relationship. 

PMID- 24569643
TI  - Low wall stress in the popliteal artery: Other mechanisms responsible for the
      predilection of aneurysmal dilatation?
AB  - The popliteal artery (PA) is, after aorta, the most common site for aneurysm
      formation. Why the PA is more susceptible than other peripheral muscular arteries
      is unknown. We hypothesized that the wall composition, which in turn affects wall
      properties, as well as the circumferential wall stress (WS) imposed on the
      arterial wall, might differ compared to other muscular arteries. The aim was to
      study the WS of the PA in healthy subjects with the adjacent, muscular, common
      femoral artery (CFA) as a comparison. Ninety-four healthy subjects were included
      in this study (45 males, aged 10-78 years and 49 females, aged 10-83 years). The
      diameter and intima-media thickness (IMT) in the PA and CFA were investigated
      with ultrasound. Together with blood pressure the WS was defined according to the
      law of Laplace adjusted for IMT. The diameter increased with age in both PA and
      CFA (p<0.001), with males having a larger diameter than females (p<0.001). IMT
      increased with age in both PA and CFA (p<0.001), with higher IMT values in males
      only in PA (p<0.001). The calculated WS was unchanged with age in both arteries,
      but lower in PA than in CFA in both sexes (p<0.001). In conclusion, this study
      shows that the PA and CFA WS is maintained during aging, probably due to a
      compensatory remodelling response with an increase in arterial wall thickness.
      However, the stress imposed on the PA wall is quite low, indicating that
      mechanisms other than WS contribute to the process of pathological arterial
      dilatation in the PA.

PMID- 24569640
TI  - Rheumatoid arthritis in the Women's Health Initiative: methods and baseline
      evaluation.
AB  - Second-generation assays for anti-cyclic citrullinated peptide (anti-CCP), a
      highly sensitive and specific marker for rheumatoid arthritis (RA), have
      redefined the epidemiology of RA. In the Women's Health Initiative (WHI) RA study
      (2009-2011), we evaluated the prevalence of anti-CCP positivity among 15,691
      (10.2% of 161,808) WHI participants aged 50-79 years who reported RA. Using
      stored baseline specimens, we measured serum anti-CCP, rheumatoid factor (RF),
      and antinuclear antibody in a defined sample of 9,988 of black, white, and
      Hispanic women. In a subset of women, we measured plasma cytokine levels and
      number of copies of the human leukocyte antigen (HLA)-DRB1 (HLA-DRB1) shared
      epitope in DNA by means of Luminex polymerase chain reaction typing (Luminex
      Corporation, Austin, Texas). We validated classification of probable clinical RA
      in 2 clinics as anti-CCP positivity or self-reported validated use of disease
      modifying antirheumatic drugs (DMARDs). The prevalence of anti-CCP positivity was
      8.1%, and the prevalence of RF positivity was approximately 16.0%. DMARD use
      including prednisone was reported by 1,140 (11.4%) participants (841 excluding
      prednisone) but by 57.5% of anti-CCP-positive women. The prevalence of 2 shared
      epitopes was also much higher for anti-CCP-positive women (18.2%, as opposed to
      only 5.5% for women with anti-CCP-negative DMARD-positive RA and 6.6% for anti
      CCP-negative, RF-negative DMARD nonusers). Median cytokine levels were much
      higher for anti-CCP-positive/RF-positive women. Women with anti-CCP-positive RA
      and anti-CCP-negative RA had different characteristics with regard to HLA shared
      epitope, cigarette smoking, and inflammation (cytokines). 

PMID- 24569644
TI  - Surrogate reporter-based enrichment of cells containing RNA-guided Cas9 nuclease
      induced mutations.
AB  - RNA-guided endonucleases (RGENs), which are based on the clustered, regularly
      interspaced, short palindromic repeat (CRISPR)-CRISPR-associated (Cas) system,
      have recently emerged as a simple and efficient tool for genome editing. However,
      the activities of prepared RGENs are sometimes low, hampering the generation of
      cells containing RGEN-induced mutations. Here we report efficient methods to
      enrich cells containing RGEN-induced mutations by using surrogate reporters.
      HEK293T cells are cotransfected with the reporter plasmid, a plasmid encoding
      Cas9 and a plasmid encoding crRNA and tracrRNA, and subjected to flow cytometric
      sorting, magnetic separation or hygromycin selection. The selected cell
      populations are highly enriched with cells containing RGEN-induced mutations, by
      a factor of up to 11-fold as compared with the unselected population. The fold
      enrichment tends to be high when RGEN activity is low. We envision that these
      reporters will facilitate the use of RGEN in a wide range of biomedical research.

PMID- 24569645
TI  - Electron induced single strand break and cyclization: a DFT study on the
      radiosensitization mechanism of the nucleotide of 8-bromoguanine.
AB  - Cleavage of the O-P bond in 8-bromo-2'-deoxyguanosine-3',5'-diphosphate (BrdGDP),
      considered as a model of single strand break (SSB) in labelled double-stranded
      DNA (ds DNA), is investigated at the B3LYP/6-31++G(d,p) level. The thermodynamic
      and kinetic characteristics of the formation of SSB are compared to those related
      to the 5',8-cycloguanosine lesion. The first reaction step, common to both damage
      types, which is the formation of the reactive guanyl radical, proceeds with a
      barrier-free or low-barrier release of the bromide anion. The guanyl radical is
      then stabilized by hydrogen atom transfer from the C3' or C5' sites of the 2'
      deoxyribose moiety to its C8 center. The C3' path, via the O-P bond cleavage,
      leads to a ketone derivative (the SSB model), while the C5' path is more likely
      to yield 5',8-cycloguanosine. 

PMID- 24569646
TI  - Deep ocean carbonate ion increase during mid Miocene CO2 decline.
AB  - Characterised by long term cooling and abrupt ice sheet expansion on Antarctica
      ~14 Ma ago, the mid Miocene marked the beginning of the modern ice-house world,
      yet there is still little consensus on its causes, in part because carbon cycle
      dynamics are not well constrained. In particular, changes in carbonate ion
      concentration ([CO3(2-)]) in the ocean, the largest carbon reservoir of the ocean
      land-atmosphere system, are poorly resolved. We use benthic foraminiferal B/Ca
      ratios to reconstruct relative changes in [CO3(2-)] from the South Atlantic, East
      Pacific, and Southern Oceans. Our results suggest an increase of perhaps ~40
      MUmol/kg may have occurred between ~15 and 14 Ma in intermediate to deep waters
      in each basin. This long-term increase suggests elevated alkalinity input,
      perhaps from the Himalaya, rather than other shorter-term mechanisms such as
      ocean circulation or ecological changes, and may account for some of the proposed
      atmospheric CO2 decline before ~14 Ma.

PMID- 24569647
TI  - A smartphone platform for the quantification of vitamin D levels.
AB  - Vitamin D deficiency has been linked to a number of diseases and adverse outcomes
      including: osteoporosis, infections, diabetes, cardiovascular diseases, and even
      cancer. At present the vast majority of vitamin D testing is performed in large
      scale laboratories at the request of a physician as part of an annual panel of
      blood tests. Here we present a system for rapid quantification of vitamin D
      levels on a smartphone. The system consists of a smartphone accessory, an app,
      and a test strip that allows the colorimetric detection of 25-hydroxyvitamin D
      using a novel gold nanoparticle-based immunoassay. We show that the system can be
      used to accurately measure physiological levels of 25-hydroxyvitamin D with
      accuracy better than 15 nM and a precision of 10 nM. We compare our system with
      well-established ELISA test kits for serum samples of unknown concentration and
      demonstrate equivalency of the results. We envision this as the first step
      towards the development of the NutriPhone, a comprehensive system for the
      analysis of multiple vitamins and micronutrients on a smartphone. 

PMID- 24569648
TI  - Highly durable fuel cell electrodes based on ionomers dispersed in glycerol.
AB  - A major, unprecedented improvement in the durability of polymer electrolyte
      membrane fuel cells is obtained by tuning the properties of the interface between
      the catalyst and the ionomer by choosing the appropriate dispersing medium. While
      a fuel cell cathode prepared from aqueous dispersion showed 90 mV loss at 0.8 A
      cm(-2) after 30,000 potential cycles (0.6-1.0 V), a fuel cell cathode prepared
      from glycerol dispersion exhibited only 20 mV loss after 70,000 cycles. This
      minimum performance loss occurs even though there was an over 80% reduction of
      electrochemical surface area of the Pt catalyst. These findings indicate that a
      proper understanding and control of the catalyst-water-ionomer (three-phase)
      interfaces is even more important for maintaining fuel cell durability in typical
      electrodes than catalyst agglomeration, and this opens up a novel path for
      tailoring the functional properties of electrified interfaces.

PMID- 24569649
TI  - Versatile chiral chromatography with mixed stationary phases of water-impregnated
      silica gel and reversed-phase packing.
AB  - A novel chiral chromatographic scheme is proposed, which requires no organic
      syntheses in stationary phase preparation. A normal phase chiral chromatography
      stationary phase is prepared by simple passage of an aqueous solution of an
      appropriate chiral selector through e.g. a silica gel column. For this scheme, a
      mixed-bed of bare silica gel and octadecylsilanized silica gel (ODS) provides
      much better separation performance than a silica gel column. Isolation of silica
      gel particles in the column is important for successful chiral separation based
      on the present scheme. 

PMID- 24569650
TI  - Tuning the entanglement between orbital reconstruction and charge transfer at a
      film surface.
AB  - The interplay between orbital, charge, spin, and lattice degrees of freedom is at
      the core of correlated oxides. This is extensively studied at the interface of
      heterostructures constituted of two-layer or multilayer oxide films. Here, we
      demonstrate the interactions between orbital reconstruction and charge transfer
      in the surface regime of ultrathin (La,Sr)MnO3, which is a model system of
      correlated oxides. The interactions are manipulated in a quantitative manner by
      surface symmetry-breaking and epitaxial strain, both tensile and compressive. The
      established charge transfer, accompanied by the formation of oxygen vacancies,
      provides a conceptually novel vision for the long-term problem of manganites--the
      severe surface/interface magnetization and conductivity deterioration. The oxygen
      vacancies are then purposefully tuned by cooling oxygen pressure, markedly
      improving the performances of differently strained films. Our findings offer a
      broad opportunity to tailor and benefit from the entanglements between orbit,
      charge, spin, and lattice at the surface of oxide films.

PMID- 24569651
TI  - Ractopamine residues in urine, plasma and hair of cattle during and after
      treatment.
AB  - The objective of this study was to investigate ractopamine residues in urine,
      plasma and hair of cattle during and after treatment. Three cattle (body weight =
      620 +/- 6.2 kg) were administered ractopamine (2.01 mg/kg body weight) into the
      rumen for 5 consecutive days. Ractopamine concentrations in samples were
      determined by an ultra-performance liquid chromatography-tandem mass spectrometry
      (UPLC-MS-MS) method. The concentrations of parent ractopamine in urine were
      1,631.1 ng/mL on withdrawal day 0 and 8.3 ng/mL on withdrawal day 14. After
      hydrolysis of its conjugates, ractopamine concentration ranged from 11,796.7
      ng/mL (withdrawal day 0) to 39.7 ng/mL (withdrawal day 14). In plasma, parent
      ractopamine and its conjugates were below the limits of quantification (LOQ = 0.2
      ng/mL) on withdrawal days 5 and 7. Accumulation of ractopamine in black and white
      hair was 124.6 and 78.1 ng/g, respectively, on withdrawal day 0, and 226.7 and
      165.6 ng/g, respectively, on withdrawal day 14. This study demonstrated the rapid
      elimination and high bioavailability of ractopamine in urine and plasma in
      cattle. However, accumulation of ractopamine in cattle's hair is high and
      persistent, so hair can be used as the target matrix for monitoring ractopamine
      abuse in ruminants. 

PMID- 24569652
TI  - Clinical feasibility of action observation training for walking function of
      patients with post-stroke hemiparesis: a randomized controlled trial.
AB  - OBJECTIVE: To identify the effects of action observation training (AOT) on the
      walking ability of subjects with post-stroke hemiparesis. DESIGN: Randomized,
      single-blind, controlled pilot study. SETTING: Inpatient rehabilitation hospital.
      SUBJECTS: Twenty-one subjects with post-stroke hemiparesis were randomly
      allocated to either the experimental group (EG) or the control group (CG), with
      11 and 10 patients, respectively. INTERVENTIONS: The subjects in the EG and CG
      watched video clips demonstrating four functional walking tasks and showing
      different landscape images, respectively. All subjects subsequently performed the
      walking tasks (a total of 30 min, once a day, 3 times weekly for a 4-week
      period). MAIN MEASURES: 10-m walk test, figure-of-8 walk test (time and steps),
      dynamic gait index (DGI), and gait symmetry score (swing and stance phases, and
      stride length) before and after the intervention. RESULTS: The changes between
      the pre- and post-test values of the 10-m walk test (median [interquartile
      range], -5.10 [-15.80--1.60] versus 0.00 [-6.60-4.06]), figure-of-8 walk test
      (time: -3.50 [-12.60--2.00] versus -1.25 [-4.98-0.25]; steps:-5.00 [-8.00--2.00]
      versus 0.00 [-3.25-0.25]), and DGI (4.00 [3.00-6.00] versus 1.00 [-4.00-3.00])
      showed significant differences between the EG and CG (p < 0.05). In the EG, the
      10-m walk test, time and steps of figure-of-8 walk test, DGI, and gait symmetry
      score in the stance phase showed significant differences between pre- and post
      test (p < 0.05). CONCLUSIONS: The findings suggest that AOT can be beneficial in
      enhancing walking ability of patients with post-stroke hemiparesis, and may be
      clinically feasible as a practical adjunct to routine rehabilitation therapy. A
      power calculation on our data showed that 20 subjects in each group were required
      for further definitive studies.

PMID- 24569653
TI  - A systematic review of factors associated with accidental falls in people with
      multiple sclerosis: a meta-analytic approach.
AB  - OBJECTIVE: To determine whether there are demographic, clinical, and instrumental
      variables useful to detect fall status of patients with multiple sclerosis. DATA
      SOURCES: PubMed and the Cochrane Library. REVIEW METHODS: Eligible studies were
      identified by two independent investigators. Only studies having a clear
      distinction between fallers and non-fallers were included and meta-analysed. Odds
      ratios (ORs) and standard mean differences (SMDs) were calculated and pooled
      using fixed effect models. RESULTS: Among 115 screened articles, 15 fulfilled
      criteria for meta-analyses, with a total of 2425 patients included. Proportion of
      fallers may vary from 30% to 63% in a time frame from 1 to 12 months. No
      significant publication bias was found, even though 12/15 studies relied on
      retrospective reports of falls, thus introducing recall biases. Risk factors for
      falls varied across studies, owing to heterogeneity of populations included and
      clinical instruments used. The meta-analytic approach found that, compared with
      non-fallers, fallers had longer disease duration (SMD = 0.14, p = 0.02),
      progressive course of disease (OR = 2.02, p < 0.0001), assistive device for
      walking (OR = 3.16, p < 0.0001), greater overall disability level (SMD = 0.74, p
      < 0.0001), slower walking speed (SMD = 0.45, p = 0.0005), and worse performances
      in balance tests (Berg Balance Scale: SMD = -0.48, p = 0.002; Timed up-and-go
      test, SMD = 0.31, p = 0.04), and force-platform measures (postural sway) with
      eyes opened (SMD = 0.71, p = 0.006) and closed (SMD = 0.83, p = 0.01),
      respectively. CONCLUSION: Elucidations regarding risk factors for accidental
      falls in patients with multiple sclerosis (PwMs) are provided here, with worse
      disability score, progressive course, use of walking aid, and poorer performances
      in static and dynamic balance tests strongly associated with fall status.

PMID- 24569655
TI  - A pause for reflection.

PMID- 24569656
TI  - Literature reviews should reveal the reviewers' rationale to opt for particular
      quality assessment criteria.

PMID- 24569657
TI  - In reply to Hannes and Aergeerts.

PMID- 24569658
TI  - Preventing illegal interview questions: the need for training skilled
      interviewers.

PMID- 24569660
TI  - Minority faculty pay a higher proportion of their earnings to student debt.

PMID- 24569659
TI  - In reply to Clancy.

PMID- 24569661
TI  - Teaching trainees to prevent medical errors may decrease the need for disclosure.

PMID- 24569663
TI  - The fifth white coat.

PMID- 24569664
TI  - A beneficent death.

PMID- 24569665
TI  - Medicine and the arts. Commentary on "laughing with," lyrics and music by Regina
      Spektor.

PMID- 24569667
TI  - AM last page: Longitudinal integrated clerkships.

PMID- 24569668
TI  - Role of pH controlled DNA secondary structures in the reversible
      dispersion/precipitation and separation of metallic and semiconducting single
      walled carbon nanotubes.
AB  - Single-stranded DNA (ss-DNA) oligomers (dA20, d[(C3TA2)3C3] or dT20) are able to
      disperse single-walled carbon nanotubes (SWNTs) in water at pH 7 through non
      covalent wrapping on the nanotube surface. At lower pH, an alteration of the DNA
      secondary structure leads to precipitation of the SWNTs from the dispersion. The
      structural change of dA20 takes place from the single-stranded to the A-motif
      form at pH 3.5 while in case of d[(C3TA2)3C3] the change occurs from the single
      stranded to the i-motif form at pH 5. Due to this structural change, the DNA is
      no longer able to bind the nanotube and hence the SWNT precipitates from its well
      dispersed state. However, this could be reversed on restoring the pH to 7, where
      the DNA again relaxes in the single-stranded form. In this way the dispersion and
      precipitation process could be repeated over and over again. Variable temperature
      UV-Vis-NIR and CD spectroscopy studies showed that the DNA-SWNT complexes were
      thermally stable even at ~90  degrees C at pH 7. Broadband NIR laser (1064 nm)
      irradiation also demonstrated the stability of the DNA-SWNT complex against local
      heating introduced through excitation of the carbon nanotubes. Electrophoretic
      mobility shift assay confirmed the formation of a stable DNA-SWNT complex at pH 7
      and also the generation of DNA secondary structures (A/i-motif) upon
      acidification. The interactions of ss-DNA with SWNTs cause debundling of the
      nanotubes from its assembly. Selective affinity of the semiconducting SWNTs
      towards DNA than the metallic ones enables separation of the two as evident from
      spectroscopic as well as electrical conductivity studies. 

PMID- 24569669
TI  - Inhaled microparticles of antitubercular antibiotic for in vitro and in vivo
      alveolar macrophage targeting and activation of phagocytosis.
AB  - Tuberculosis (TB) is a chronic infectious disease with increasing incidence of
      drug resistance. Oral treatment for TB and multidrug resistance-TB can have
      serious side effects. The causative agent of TB, Mycobacterium tuberculosis,
      resides in alveolar macrophages (AMs). Pulmonary administration of antitubercular
      (anti-TB) antibiotic can help in delivery of high concentration to AM. The
      ability of AM to phagocytose can also be utilized to generate mycobactericidal
      nitric oxide (NO) to improve efficacy of anti-TB antibiotics. The objective in
      this investigation was made to prepare isoniazid microparticles (IM) and
      polymeric microparticles of isoniazid (INH-PM) using poly-epsilon-caprolactone as
      polymer and to evaluate in vitro through cell culture techniques and in vivo
      through pulmonary administration of IM and INH-PM for uptake of isoniazid by AM.
      The hepatotoxicity was determined through serum glutamate oxaloacetate
      transferase (SGOT) and serum glutamate pyruvate transferase (SGPT) levels and
      histological examination. The results depicted that the significantly higher
      (P<0.05) concentration of isoniazid was found in AM with INH-PM in vitro and in
      vivo. NO production was also significantly higher but less than toxic level. SGOT
      and SGPT levels, uptake of INH by liver and histological examination were
      indicative of no hepatotoxicity with INH-PM and IM. Phagocytosis of IM and INH-PM
      leads to significantly higher drug level in AM as well as production of
      significantly higher levels of NO without compromising the viability of cells.
      The administration of IM and INH-PM as dry powder inhalation formulation may
      reduce the treatment time of TB and chances of drug-resistant TB. 

PMID- 24569670
TI  - Graminin B, a furanone from the fungus Paraconiothyrium sp.

PMID- 24569671
TI  - Dereplication of microbial extracts and related analytical technologies.
AB  - Natural products still continue to have an important role as a resource of
      various biologically active substances. Dereplication is a key process in natural
      product screening that analyzes the extracts of microbial fermentation broths or
      plant samples. In this review article, we describe and discuss the analytical
      techniques of dereplication and related technologies in the following sections:
      1. Direct detection from microbial colonies. 2. Ultra high performance liquid
      chromatography (UHPLC)-MS profiling for library construction. 3. Micro
      fractionation to identify active peaks. 4. Quantification of small-amount
      compounds. 5. Structure identification from small amounts. Using these
      techniques, the desired compound in the mixture library can be rapidly
      identified. 

PMID- 24569672
TI  - Atomically thin nonreciprocal optical isolation.
AB  - Optical isolators will play a critical role in next-generation photonic circuits,
      but their on-chip integration requires miniaturization with suitable
      nonreciprocal photonic materials. Here, we theoretically demonstrate the thinnest
      possible and polarization-selective nonreciprocal isolation for circularly
      polarized waves by using graphene monolayer under an external magnetic field. The
      underlying mechanism is that graphene electron velocity can be largely different
      for the incident wave propagating in opposite directions at cyclotron frequency,
      making graphene highly conductive and reflective in one propagation direction
      while transparent in the opposite propagation direction under an external
      magnetic field. When some practical loss is introduced, nonreciprocal isolation
      with graphene monolayer still possesses good performance in a broad bandwidth.
      Our work shows the first study on the extreme limit of thickness for optical
      isolation and provides theoretical guidance in future practical applications. 

PMID- 24569673
TI  - Basal microRNA expression patterns in reward circuitry of selectively bred high
      responder and low-responder rats vary by brain region and genotype.
AB  - Mental health disorders involving altered reward, emotionality, and anxiety are
      thought to result from the interaction of individual predisposition (genetic
      factors) and personal experience (environmental factors), although the mechanisms
      that contribute to an individual's vulnerability to these disorders remain poorly
      understood. We used an animal model of individual variation [inbred high
      responder/low-responder (bHR-bLR) rodents] known to vary in reward, anxiety, and
      emotional processing to examine neuroanatomical expression patterns of microRNAs
      (miRNAs). Laser capture microdissection was used to dissect the prelimbic cortex
      and the nucleus accumbens core and shell prior to analysis of basal miRNA
      expression in bHR and bLR male rats. These studies identified 187 miRNAs
      differentially expressed by genotype in at least one brain region, 10 of which
      were validated by qPCR. Four of these 10 qPCR-validated miRNAs demonstrated
      differential expression across multiple brain regions, and all miRNAs with
      validated differential expression between genotypes had lower expression in bHR
      animals compared with bLR animals. microRNA (miR)-484 and miR-128a expression
      differences between the prelimbic cortex of bHR and bLR animals were validated by
      semiquantitative in situ hybridization. miRNA expression analysis independent of
      genotype identified 101 miRNAs differentially expressed by brain region, seven of
      which validated by qPCR. Dnmt3a mRNA, a validated target of miR-29b, varied in a
      direction opposite that of miR-29b's differential expression between bHR and bLR
      animals. These data provide evidence that basal central nervous system miRNA
      expression varies in the bHR-bLR model, implicating microRNAs as potential
      epigenetic regulators of key neural circuits and individual differences
      associated with mental health disorders. 

PMID- 24569674
TI  - Prepartal dietary energy alters transcriptional adaptations of the liver and
      subcutaneous adipose tissue of dairy cows during the transition period.
AB  - Overfeeding during the dry period may predispose cows to increased insulin
      resistance (IR) with enhanced postpartum lipolysis. We studied gene expression in
      the liver and subcutaneous adipose tissue (SAT) of 16 Finnish Ayrshire dairy cows
      fed either a controlled energy diet [Con, 99 MJ/day metabolizable energy (ME)]
      during the last 6 wk of the dry period or high-energy diet (High, 141 MJ/day ME)
      for the first 3 wk and then gradually decreasing energy allowance during 3 wk to
      99 MJ/day ME before the expected parturition. Tissue biopsies were collected at 
      10, 1, and 9 days, and blood samples at -10, 1, and 7 days relative to
      parturition. Overfed cows had greater dry matter, crude protein, and ME intakes
      and ME balance before parturition. Daily milk yield, live weight, and body
      condition score were not different between treatments. The High cows tended to
      have greater plasma insulin and lower glucagon/insulin ratio compared with Con
      cows. No differences in circulating glucose, glucagon, nonesterified fatty acids
      and beta-hydroxybutyrate concentrations, and hepatic triglyceride contents were
      observed between treatments. Overfeeding compared with Con resulted in lower
      CPT1A and PCK1 and a tendency for lower G6PC and PC expression in the liver. The
      High group tended to have lower RETN expression in SAT than Con. No other effects
      of overfeeding on the expression of genes related to IR in SAT were observed. In
      conclusion, overfeeding energy prepartum may have compromised hepatic
      gluconeogenic capacity and slightly affected IR in SAT based on gene expression. 

PMID- 24569676
TI  - Owning your role.

PMID- 24569677
TI  - Lateral violence and the exit strategy.

PMID- 24569675
TI  - Electron uptake by iron-oxidizing phototrophic bacteria.
AB  - Oxidation-reduction reactions underlie energy generation in nearly all life
      forms. Although most organisms use soluble oxidants and reductants, some microbes
      can access solid-phase materials as electron-acceptors or -donors via
      extracellular electron transfer. Many studies have focused on the reduction of
      solid-phase oxidants. Far less is known about electron uptake via microbial
      extracellular electron transfer, and almost nothing is known about the associated
      mechanisms. Here we show that the iron-oxidizing photoautotroph Rhodopseudomonas
      palustris TIE-1 accepts electrons from a poised electrode, with carbon dioxide as
      the sole carbon source/electron acceptor. Both electron uptake and ruBisCo form I
      expression are stimulated by light. Electron uptake also occurs in the dark,
      uncoupled from photosynthesis. Notably, the pioABC operon, which encodes a
      protein system essential for photoautotrophic growth by ferrous iron oxidation,
      influences electron uptake. These data reveal a previously unknown metabolic
      versatility of photoferrotrophs to use extracellular electron transfer for
      electron uptake. 

PMID- 24569678
TI  - Embracing a culture of safety by decreasing medication errors.

PMID- 24569680
TI  - Planting seeds of succession.

PMID- 24569681
TI  - Not just for cars: Lean methodology.

PMID- 24569682
TI  - Relational work: at the core of leadership.

PMID- 24569683
TI  - Leadership by design: creating successful "TEEAMS".

PMID- 24569684
TI  - Retiring with flair.

PMID- 24569685
TI  - Differential protective effects of red wine polyphenol extracts (RWEs) on colon
      carcinogenesis.
AB  - Various epidemiological studies have shown that a regular and moderate
      consumption of red wine is correlated with a decreased relative risk of
      developing coronary heart disease and cancer. These health benefits are commonly
      attributed to high contents of polyphenols, particularly resveratrol,
      representing important sources of antioxidants. However, resveratrol does not
      seem to be the only bioactive compound present in the wine which contains
      numerous other polyphenols. The present study investigates the efficiency of red
      wine extracts (RWEs), containing different polyphenols, on colon cancer cell
      proliferation in vitro and on colonic aberrant crypt foci (ACF) in vivo.
      Proliferation, cell cycle analysis and incidence of ACF were monitored to examine
      the effects of RWEs. RWEs derived from a long vinification process exhibit
      superior anti-proliferative activity in colon cancer cells and prevent the
      appearance of ACF in mice. Interestingly, quercetin and resveratrol, representing
      two major bio-active polyphenols, exhibit synergistic anti-proliferative effects.
      These data suggest that the efficacy of RWEs on colon carcinogenesis may depend
      on the polyphenolic content, synergistic interaction of bio-active polyphenols
      and modulation of cellular uptake of polyphenols.

PMID- 24569686
TI  - Tracking the progression of social cognition in neurodegenerative disorders.
AB  - BACKGROUND AND PURPOSE: Behavioural-variant frontotemporal dementia (bvFTD) and
      Alzheimer's disease (AD) patients experience behavioural and emotion recognition
      alterations, yet understanding of how socioemotional processing is affected with
      disease progression is minimal. Additionally, evidence suggests that bvFTD
      patients with limited brain atrophy on neuroimaging at presentation (bvFTD-la)
      have a more benign course than those with marked atrophy (bvFTD-ma). Longitudinal
      investigation of these patients, however, is lacking. METHODS: We investigated
      general cognition, emotion recognition and sarcasm detection in 20 bvFTD (8 with
      limited brain atrophy) and 17 AD patients longitudinally and used mixed models
      analyses to determine the level and rates of decline across groups over time.
      RESULTS: At baseline, all patient groups performed worse than controls on general
      cognition and emotion recognition measures. The bvFTD-ma group showed significant
      impairment on the sarcasm detection task compared with controls. Longitudinally,
      an overall effect of time was present for general cognition (p<0.001); however,
      the rate of decline did not differ across groups. Trends for interactions between
      time and diagnosis were observed for both emotion recognition tasks (p=0.055;
      p=0.062), with the bvFTD-ma group declining more rapidly than AD or bvFTD-la
      groups. On the sarcasm detection task, the bvFTD-ma and AD patients declined,
      whereas bvFTD-la patients remained stable over time (p=0.002). CONCLUSIONS: Tasks
      of sarcasm detection represent a clinically useful tool to differentiate between
      bvFTD and AD at baseline. Furthermore, tasks of socioemotional functioning can
      track progression within bvFTD and identify bvFTD patients more likely to show a
      faster rate of decline.

PMID- 24569687
TI  - Tobacco smoking and excess mortality in multiple sclerosis: a cohort study.
AB  - OBJECTIVE: As patients with multiple sclerosis (MS) have more than 2.5-fold
      increased mortality risk, we sought to investigate the impact of tobacco smoking
      on the risk of premature death and its contribution to the excess mortality in MS
      patients. METHODS: We studied 1032 patients during the period 1994-2013 in a UK
      based register. Cox regression model was used to investigate the impact of
      smoking on the risk of premature death, controlling for confounders. Smoking
      specific mortality rates were compared with the UK general population. RESULTS:
      Of 923 patients with clinically definite MS, 80 (46 males and 34 females) had
      died by December 2012. HRs for death in current smokers and ex-smokers relative
      to never smokers were 2.70 (95% CI 1.59 to 4.58, p<0.001) and 1.30 (95% CI 0.72
      to 2.32; p = 0.37). The standardised mortality ratio, compared with the UK
      general population, when stratified by smoking status was 3.83 (95% CI 2.71 to
      5.42) in current smokers, 1.96 (95% CI 1.27 to 3.0) in ex-smokers and 1.27 (95%
      CI 0.87 to 1.86) in non-smokers. Never smokers and ex-smokers with MS had similar
      mortality rates compared with never smokers and ex-smokers without MS in the male
      British doctors cohort (1.12 (95% CI 0.63 to 1.97) and 0.54 (95% CI 0.26 to
      1.14), respectively), while current smokers with MS had 84% higher rate of death
      compared with current smokers without MS (95% CI 1.24 to 2.72). CONCLUSIONS:
      Tobacco smoking can account for some of the excess mortality associated with MS
      and is a risk determinant for all-cause and MS-related death.

PMID- 24569688
TI  - Attention! A good bedside test for delirium?
AB  - BACKGROUND: Routine delirium screening could improve delirium detection, but it
      remains unclear as to which screening tool is most suitable. We tested the
      diagnostic accuracy of the following screening methods (either individually or in
      combination) in the detection of delirium: MOTYB (months of the year backwards);
      SSF (Spatial Span Forwards); evidence of subjective or objective 'confusion'.
      METHODS: We performed a cross-sectional study of general hospital adult
      inpatients in a large tertiary referral hospital. Screening tests were performed
      by junior medical trainees. Subsequently, two independent formal delirium
      assessments were performed: first, the Confusion Assessment Method (CAM) followed
      by the Delirium Rating Scale-Revised 98 (DRS-R98). DSM-IV (Diagnostic and
      Statistical Manual of Mental Disorders, fourth edition) criteria were used to
      assign delirium diagnosis. Sensitivity and specificity ratios with 95% CIs were
      calculated for each screening method. RESULTS: 265 patients were included. The
      most precise screening method overall was achieved by simultaneously performing
      MOTYB and assessing for subjective/objective confusion (sensitivity 93.8%, 95% CI
      82.8 to 98.6; specificity 84.7%, 95% CI 79.2 to 89.2). In older patients, MOTYB
      alone was most accurate, whereas in younger patients, a simultaneous combination
      of SSF (cut-off 4) with either MOTYB or assessment of subjective/objective
      confusion was best. In every case, addition of the CAM as a second-line screening
      step to improve specificity resulted in considerable loss in sensitivity.
      CONCLUSIONS: Our results suggest that simple attention tests may be useful in
      delirium screening. MOTYB used alone was the most accurate screening test in
      older people.

PMID- 24569691
TI  - Police investigate work of UK colorectal surgeon after patients die.

PMID- 24569689
TI  - Neurons have an active glycogen metabolism that contributes to tolerance to
      hypoxia.
AB  - Glycogen is present in the brain, where it has been found mainly in glial cells
      but not in neurons. Therefore, all physiologic roles of brain glycogen have been
      attributed exclusively to astrocytic glycogen. Working with primary cultured
      neurons, as well as with genetically modified mice and flies, here we report that
      against general belief-neurons contain a low but measurable amount of glycogen.
      Moreover, we also show that these cells express the brain isoform of glycogen
      phosphorylase, allowing glycogen to be fully metabolized. Most importantly, we
      show an active neuronal glycogen metabolism that protects cultured neurons from
      hypoxia-induced death and flies from hypoxia-induced stupor. Our findings change
      the current view of the role of glycogen in the brain and reveal that endogenous
      neuronal glycogen metabolism participates in the neuronal tolerance to hypoxic
      stress. 

PMID- 24569690
TI  - Recombinant human interleukin-1 receptor antagonist in severe traumatic brain
      injury: a phase II randomized control trial.
AB  - Traumatic brain injury (TBI) is the commonest cause of death and disability in
      those aged under 40 years. Interleukin-1 receptor antagonist (IL1ra) is an
      endogenous competitive antagonist at the interleukin-1 type-1 receptor (IL-1R).
      Antagonism at the IL-1R confers neuroprotection in several rodent models of
      neuronal injury (i.e., trauma, stroke and excitotoxicity). We describe a single
      center, phase II, open label, randomized-control study of recombinant human IL1ra
      (rhIL1ra, anakinra) in severe TBI, at a dose of 100 mg subcutaneously once a day
      for 5 days in 20 patients randomized 1:1. We provide safety data (primary
      outcome) in this pathology, utilize cerebral microdialysis to directly determine
      brain extracellular concentrations of IL1ra and 41 cytokines and chemokines, and
      use principal component analysis (PCA) to explore the resultant cerebral cytokine
      profile. Interleukin-1 receptor antagonist was safe, penetrated into plasma and
      the brain extracellular fluid. The PCA showed a separation in cytokine profiles
      after IL1ra administration. A candidate cytokine from this analysis, macrophage
      derived chemoattractant, was significantly lower in the rhIL1ra-treated group.
      Our results provide promising data for rhIL1ra as a therapeutic candidate by
      showing safety, brain penetration and a modification of the neuroinflammatory
      response to TBI by a putative neuroprotective agent in humans for the first time.

PMID- 24569694
TI  - Computational screening of structural and compositional factors for electrically
      conductive coordination polymers.
AB  - The combination of organic and inorganic chemical building blocks to form metal
      organic frameworks (MOFs) offers opportunities for producing functional materials
      suitable for energy generation, storage and conversion. However, such
      applications rely on robust electron transport and the design of conductive
      hybrid materials is still in its infancy. Here we apply density functional theory
      to assess the important structural and compositional factors for forming
      conducting MOFs. We focus on 1D metal-organic polymers as a model system and
      assess the choice of organic, inorganic and linking units. The results
      demonstrate that electronic communication is sensitive to the energy and symmetry
      of the frontier orbitals associated with the organic and inorganic building
      blocks and offers guidance on how to optimise electrical conduction in hybrid
      materials. 

PMID- 24569693
TI  - Comparisons of auditory steady state response and behavioral air conduction and
      bone conduction thresholds for infants and adults with normal hearing.
AB  - OBJECTIVE: To improve understanding of normal responses in infants by comparing
      air conduction (AC) and bone conduction (BC) auditory thresholds using both the
      auditory steady state response (ASSR) and behavioral testing methods in normal
      hearing infants (6 to 18 months of age) and adults. At present, there are no
      correction factors available for estimating BC behavioral thresholds from BC ASSR
      thresholds, which is a barrier to clinical implementation of the ASSR. In
      addition, previous studies have reported infant-adult differences in AC and BC
      sensitivity, which suggest a "maturational" air-bone gap (ABG) that is not
      attributable to a conductive pathology; no study has yet compared AC and BC
      thresholds for either ASSR or behavioral methods in the same individuals. The
      objectives of the present study are: (1) to compare BC thresholds between methods
      and provide the initial step toward positing correction factors to predict BC
      behavioral thresholds, (2) to directly compare AC and BC thresholds to provide an
      accurate estimate of the maturational ABG, (3) to determine preliminary normal
      levels for BC and AC ASSRs to exponentially amplitude modulated stimuli, and (4)
      to investigate infant-adult differences in AC and BC thresholds using ASSRs and
      behavioral assessment tools. DESIGN: Participants were 23 infants (6.5 to 19.0
      months of age) and 12 adults (17 to 50 years of age) with normal hearing.
      Thresholds were estimated at 500, 1000, 2000, and 4000 Hz using air- and bone
      conducted stimuli for ASSRs and behavioral testing. The ASSR stimuli were
      exponential envelope modulated (amplitude modulation [AM]) at modulation
      frequencies of 78, 85, 93, and 101 Hz for 500, 1000, 2000, and 4000 Hz,
      respectively, presented simultaneously. Frequency-modulated (warble tone) stimuli
      were used for behavioral testing for both infants and adults, respectively. All
      stimuli were calibrated in dB HL. Thresholds were compared across frequency and
      between stimulus presentation modes, between age groups and assessment method.
      Normal levels for AC and BC ASSRs to AM stimuli were also calculated. RESULTS:
      The findings indicated that BC thresholds were, on average, 7 to 16 dB poorer for
      ASSR compared with visual reinforcement audiometry (VRA), but varied widely
      across infants. For infants, mean ABGs of 14 to 17 dB were found for low
      frequency ASSR thresholds but mean ABGs for VRA thresholds were less than 10 dB.
      The preliminary normal levels for ASSR AM stimuli at 500, 1000, 2000, and 4000
      Hz, respectively, were: (i) AC: 30, 30, 20, and 20 dB HL, and (ii) BC: 20, 20,
      30, and 30 dB HL. There was a tendency for infant and adult ASSR thresholds to
      differ for BC, but not for AC. Behavioral thresholds for AC and BC were similar
      between infants and adults and across frequency. CONCLUSIONS: Infant-adult and AC
      BC threshold differences are greater for ASSRs compared with behavioral measures.
      The results support the presence of a clinically significant maturational ABG in
      the low frequencies for infant ASSRs but not for VRA. The findings also show a
      significant offset between BC ASSR and BC VRA thresholds and large intersubject
      variability.

PMID- 24569696
TI  - Magnetic field modulation of chirooptical effects in magnetoplasmonic structures.
AB  - In this work we analyse the magnetic field effects on the chirooptical properties
      of magnetoplasmonic chiral structures. The structures consist of two-dimensional
      arrays of Au gammadions in which thin layers of Co have been inserted. Due to the
      magnetic properties of the Au/Co interface the structures have perpendicular
      magnetic anisotropy which favours magnetic saturation along the surface normal,
      allowing magnetic field modulation of the chirooptical response with moderate
      magnetic fields. These structures have two main resonances. The resonance at 850
      nm has a larger chirooptical response than the resonance at 650 nm, which, on the
      other hand, exhibits a larger magnetic field modulation of its chirooptical
      response. This dissimilar behaviour is due to the different physical origin of
      the chirooptical and magneto-optical responses. Whereas the chirooptical effects
      are due to the geometry of the structures, the magneto-optical response is
      related to the intensity of the electromagnetic field in the magnetic (Co)
      layers. We also show that the optical chirality can be modulated by the applied
      magnetic field, which suggests that magnetoplasmonic chiral structures could be
      used to develop new strategies for chirooptical sensing. 

PMID- 24569695
TI  - Markers of inflammation and stress distinguish subsets of individuals with
      schizophrenia and bipolar disorder.
AB  - Schizophrenia and bipolar disorder share a number of common features, both
      symptomatically and biologically. Abnormalities in the neuroimmune and the stress
      signaling pathways have been previously identified in brains of individuals with
      both diseases. However, the possible relationship between abnormalities in stress
      and neuroimmune signaling within the cortex of people with psychotic illness has
      not been defined. To test the hypothesis that combined alterations in brain
      stress responsiveness and neuroimmune/inflammatory status are characteristic of
      some individuals suffering from major mental illness, we examined gene expression
      in the Stanley Array Cohort of 35 controls, 35 individuals with schizophrenia and
      34 individuals with bipolar disorder. We used levels of 8 inflammatory-related
      transcripts, of which SERPINA3 was significantly elevated in individuals with
      schizophrenia (F(2,88)=4.137, P<0.05), and 12 glucocorticoid receptor signaling
      (stress) pathway transcripts previously examined, to identify two clusters of
      individuals: a high inflammation/stress group (n=32) and a low (n=68)
      inflammation/stress group. The high inflammation/stress group has a significantly
      greater number of individuals with schizophrenia (n=15), and a trend toward
      having more bipolar disorder individuals (n=11), when compared with controls
      (n=6). Using these subgroups, we tested which microarray-assessed transcriptional
      changes may be associated with high inflammatory/stress groups using ingenuity
      analysis and found that an extended network of gene expression changes involving
      immune, growth factors, inhibitory signaling and cell death factors also
      distinguished these groups. Our work demonstrates that some of the heterogeneity
      in schizophrenia and bipolar disorder may be partially explained by
      inflammation/stress interactions, and that this biological subtype cuts across
      Diagnostic and Statistical Manual of Mental Disorders (DSM)-defined categories.

PMID- 24569697
TI  - Stressors may compromise medication adherence among adults with diabetes and low
      socioeconomic status.
AB  - Studies examining the impact of stressors on diabetes self-care have focused on a
      single stressor or have been largely qualitative. Therefore, we assessed the
      stressors experienced by a high-risk population with type 2 diabetes, and tested
      whether having more stressors was associated with less adherence to multiple self
      care behaviors. Participants were recruited from a Federally Qualified Health
      Center and 192 completed a stressors checklist. Experiencing more stressors was
      associated with less adherence to diet recommendations and medications among
      participants who were trying to be adherent, but was not associated with
      adherence to other self-care behaviors. Because having more stressors was also
      associated with more depressive symptoms, we further adjusted for depressive
      symptoms. Stressors remained associated with less adherence to medications, but
      not to diet recommendations. For adults engaged in adherence, experiencing an
      accumulation of stressors presents barriers to adherence that are distinct from
      associated depressive symptoms. 

PMID- 24569698
TI  - Medical assistant coaching to support diabetes self-care among low-income
      racial/ethnic minority populations: randomized controlled trial.
AB  - Innovative, culturally tailored strategies are needed to extend diabetes
      education and support efforts in lower-resourced primary care practices serving
      racial/ethnic minority groups. A randomized controlled trial (RCT) examined the
      effect of a diabetes self-care coaching intervention delivered by medical
      assistants and the joint effect of intervention and ethnicity over time. The
      randomized repeated-measures design included 270 low-income African American and
      Hispanic/Latino patients with type 2 diabetes. The 1-year clinic- and telephone
      based medical assistant coaching intervention was culturally tailored and guided
      by theoretical frameworks. A1C was obtained, and a self-care measure was
      completed at baseline, 6 months, and 12 months. Data were analyzed using mixed
      effects models with and without adjustment for covariates. There was a
      significant overall improvement in mean self-care scores across time, but no
      intervention effect. Results revealed differences in self-care patterns across
      racial/ethnic subgroups. No differences were found for A1C levels across time or
      group. 

PMID- 24569699
TI  - Reducing HIV stigma among nursing students: a brief intervention.
AB  - HIV stigma can be devastating and is common among health care providers,
      particularly nurses. The objectives of this study were to (a) assess the
      acceptability and feasibility of a brief stigma-reduction curriculum among a
      convenience sample of Indian nursing students and (b) examine the preliminary
      effect of this curriculum on their knowledge, attitudes, and intent to
      discriminate. At baseline, 57% of students had at least one misconception about
      HIV transmission, 38% blamed people living with HIV for their infection, and 87%
      and 95% demonstrated intent to discriminate while dispensing medications and
      drawing blood, respectively. Following the curriculum, HIV-related knowledge
      increased while blame, endorsement of coercive policies, and intent to
      discriminate decreased significantly. In addition, more than 95% of participants
      described the curriculum as practice changing. This brief intervention resulted
      in decreased stigma levels and was also highly acceptable to the nursing
      students. Next steps include rigorous evaluation in a randomized controlled
      trial. 

PMID- 24569701
TI  - Structural and functional features of a collagen-binding matrix protein from the
      mussel byssus.
AB  - Blue mussels adhere to surfaces by the byssus, a holdfast structure composed of
      individual threads representing a collagen fibre reinforced composite. Here, we
      present the crystal structure and function of one of its matrix proteins, the
      proximal thread matrix protein 1, which is present in the proximal section of the
      byssus. The structure reveals two von Willebrand factor type A domains linked by
      a two-beta-stranded linker yielding a novel structural arrangement. In vitro, the
      protein binds heterologous collagens with high affinity and affects collagen
      assembly, morphology and arrangement of its fibrils. By providing charged surface
      clusters as well as insufficiently coordinated metal ions, the proximal thread
      matrix protein 1 might interconnect other byssal proteins and thereby contribute
      to the integrity of the byssal threads in vivo. Moreover, the protein could be
      used for adjusting the mechanical properties of collagen materials, a function
      likely important in the natural byssus. 

PMID- 24569700
TI  - Mycobacterium avium paratuberculosis infection augments innate immune responses
      following intestinal epithelial injury.
AB  - We wanted to determine if augmented innate immune activation is associated with
      lesion development in a mycobacterial enhanced intestinal injury model. We
      evaluated the local immune response in a Mycobacterium avium paratuberculosis +
      dextran sulfate sodium (Map + DSS) model using BALB/c and severe combined
      immunodeficient (SCID) mice. Map + DSS BALB/c and SCID mice displayed a similar
      disease phenotype. Moreover, Map + DSS SCID mice had increased expression of
      interleukin 1beta (IL-1beta), tumor necrosis factor alpha (TNF-alpha), inducible
      nitric oxide synthase (iNOS) and increased numbers of F4/80 positive cells.
      Additionally, Map antigen is co-localized with iNOS and IL-1beta positive cells.
      This suggests that subclinical Map infection promotes innate immune activation
      following injury to the intestinal epithelium.

PMID- 24569702
TI  - Posterior sternoclavicular joint injuries in the adolescent population: a meta
      analysis.
AB  - BACKGROUND: Sternoclavicular dislocations are relatively infrequent and are
      generally divided into anterior and posterior disruptions, the former being the
      most common. While posterior sternoclavicular joint (PSCJ) injuries are very
      rare, they may be associated with life-threatening complications. The ideal
      management of these injuries, particularly in the adolescent population, has not
      been well described. PURPOSE: Through a meta-analysis of PSCJ injuries in the
      adolescent, we aimed to (1) describe the epidemiology of PSCJ injuries in
      relation to the mechanism of injury, associated complications, and treatment
      preferences; (2) compare the success of closed reduction when attempted <48
      versus >48 hours after the initial injury; and (3) compare the outcomes of closed
      versus open treatment. STUDY DESIGN: Meta-analysis. METHODS: A thorough review of
      the English literature was performed to identify all cases of PSCJ dislocations
      or medial clavicular physeal fractures in patients aged 12 to 18 years. Patient
      level data for 140 patients were extracted from 79 studies. RESULTS: The mean age
      of the patients was 15.24 years. Forty-nine patients (35.00%) underwent closed
      treatment only, 42 (30.00%) open treatment alone, and 47 (33.57%) closed
      treatment followed by open treatment. Also, 55.8% of closed reductions performed
      within 48 hours were successful compared with 30.8% of those performed more than
      48 hours after injury. After initial treatment, 92.31% of patients treated with
      closed reduction regained full function without recurrence as compared with
      95.83% of patients treated operatively. CONCLUSION: Closed and open methods have
      proven highly effective for the treatment of PSCJ injuries. However, follow-up
      data reported in the literature vary considerably. Closed reduction is most
      effective when attempted less than 48 hours after the initial injury.

PMID- 24569703
TI  - Assessing the effectiveness of neuromuscular training programs in reducing the
      incidence of anterior cruciate ligament injuries in female athletes: a systematic
      review.
AB  - BACKGROUND: Anterior cruciate ligament (ACL) injuries are more common in female
      athletes because of anatomic and biomechanical factors. These injuries can have
      detrimental ramifications for the athlete and the health care system.
      Neuromuscular training programs have been designed to modify risk factors and
      prevent ACL injuries. PURPOSE: This systematic review evaluates studies that
      assess the effectiveness of neuromuscular training programs in reducing ACL
      injuries in female athletes and provides an update to 2 previously published
      reviews. STUDY DESIGN: Systematic review. METHODS: Medline, Cochrane, and CINAHL
      databases were searched for relevant journal articles published from 1995 to
      2011. We performed a manual review of relevant articles, authors, and journals,
      including bibliographies from identified articles. Ten studies were included in
      this review. RESULTS: Only 2 studies demonstrated a statistically significant
      decrease in ACL injuries with neuromuscular training programs. Two additional
      studies showed a statistically significant decrease in subgroup analyses only.
      Four studies did show a trend toward reduced ACL injuries with neuromuscular
      training programs but were unable to achieve statistical significance.
      Neuromuscular training programs utilizing plyometric exercises and a preseason
      component were the most beneficial. Two studies actually showed an increase in
      injuries with intervention programs. CONCLUSION: Neuromuscular training programs
      may be a useful adjunct to training, but current literature precludes our
      universal recommendation of them.

PMID- 24569704
TI  - The effect of coach education on reporting of concussions among high school
      athletes after passage of a concussion law.
AB  - BACKGROUND: Increasing attention has been paid to concussions and especially
      sports-related concussions in youth. To prevent an inappropriate return to play
      while symptomatic, nearly all states have now passed legislation on youth sports
      related concussions. PURPOSE: To determine (1) the incidence of sports-related
      concussions in high school athletes using a unique system to collect reports on
      concussions, (2) the proportion of athletes with concussions who play with
      concussive symptoms, and (3) the effect of the type and modality of coach
      education on the likelihood of athletes reporting symptoms to the coach or
      playing with concussive symptoms. STUDY DESIGN: Cohort study; Level of evidence,
      2. METHODS: This study was conducted with high school football and girls' soccer
      athletes playing in fall 2012 and their coaches and parents in 20 urban or rural
      high schools in Washington State. The main outcome was the incidence of
      concussions per 1000 athlete-exposures (AEs), the proportion of concussed
      athletes who played with concussive symptoms, and the association of coach
      concussion education with coach awareness of athletes with concussive symptoms.
      RESULTS: Among the 778 athletes, the rate of concussions was 3.6 per 1000 AEs and
      was identical for the 2 sports studied. The cumulative concussion incidence over
      the course of the season was similar in girls' soccer (11.1%) and football
      (10.4%). Sixty-nine percent of concussed athletes reported playing with symptoms,
      and 40% reported that their coach was not aware of their concussion. Most
      measures of coach concussion education were not associated with coach awareness
      of concussions in their athletes, although the modalities of a video and quiz
      were associated with a lower likelihood of coach awareness. CONCLUSION: More
      objective and accurate methods are needed to identify concussions. Changes in
      athlete attitudes on reporting concussive symptoms will likely not be
      accomplished through legislation alone.

PMID- 24569705
TI  - Reference-free thyroid uptake measurement.
AB  - PURPOSE: An easy-to-implement scintigraphic method that enables the assay of
      thyroid iodine uptake with improved accuracy and without the use of a reference
      source was developed with an aim to avoid unnecessary high radiation burden to
      patients undergoing (131)I treatment for benign thyroid disease. MATERIALS AND
      METHODS: Dual-energy (123)I planar imaging involving simultaneous recording of
      both the primary (159 keV) and scatter (130 keV) frames was followed by
      generation of subtraction 'scatter-free' images. A uniform cutoff level of 15%
      was chosen to delineate the functional thyroid tissue with the help of isocontour
      regions of interest, which in turn enabled quantitation of the scatter-free
      thyroid counts. The ratio of the total counts being recorded in each of the above
      frames, the 'primary-to-Compton' ratio, was determined and compared with the
      uniform absorption-free ratio ascribed to all of the thyroid images. This enabled
      determination of the upscaling factor needed to restore the scatter-free counts
      to their unmoderated level. The corrected count content was subsequently
      converted to the iodine dose accumulated by the thyroid with the help of the
      camera-specific net detection efficiency. As a result, the true uptake value
      could be determined without the need to image a reference source or phantom.
      RESULTS: Clinical evaluation of the proposed reference-free method was carried
      out by reviewing the 24-h uptake values obtained for the 32 patients suffering
      from Graves' disease, multinodular struma, or autonomous nodule. A comparison
      with concurrently assayed thyroid uptake values derived from the counts of the 24
      h urine samples measured by the well-type scintillation counter (direct assay
      method) revealed very good linear correlation (r > 0.96). Furthermore, a
      comparison with uptake values determined using the 159 keV images of the patient
      as well as those of the reference sample in a commonly used so-called 'classic'
      manner was also carried out. The outcomes of the classic assay were found on
      average to underestimate the thyroid uptake in absolute terms by ~ 25% because of
      unattended scatter and absorption-induced count losses. In contrast, the results
      of the reference-free method exhibited slight overestimation only, which on
      average amounted to less than 2%. However, because of the time-related
      fluctuations of the gamma camera and the dose calibrator as well as uncertainties
      induced by the scatter and absorption corrections, the average relative error
      associated with thyroid uptake values as determined by the proposed reference
      free method was found to amount to nearly 10%. CONCLUSION: Strong evidence in
      support of the validity of the reference-free method designed to measure thyroid
      uptake with improved accuracy and without relating to a reference phantom image
      was produced in a clinical setting. As a result, the unnecessary high radiation
      burden to patients undergoing (131)I therapy because of systematic uptake
      underestimation could be avoided.

PMID- 24569706
TI  - Retention of 99mTc-DMSA(III) and 99mTc-nanocolloid in different syringes affects
      imaging quality.
AB  - (99m)Tc-dimercaptosuccinic acid [DMSA(III)] and colloidal human serum albumin
      ((99m)Tc-nanocolloid) are widely used radiopharmaceuticals. Recently, in our
      institution we encountered image quality problems in DMSA scans after changing
      the brand of syringes we were using, which triggered us to look into the
      adsorption properties of syringes from different brands for (99m)Tc-DMSA(III) and
      (99m)Tc-nanocolloid. We also describe a clinical case in which adsorption of
      (99m)Tc-DMSA(III) caused inferior imaging quality. DMSA and nanocolloid were
      labeled with (99m)Tc following manufacturer guidelines. After synthesis, syringes
      with (99m)Tc-DMSA(III) and (99m)Tc-nanocolloid were stored for 15, 30, 60, and
      120 min. We evaluated Luer Lock syringes manufactured by different brands such as
      Artsana, Henke-Sass-Wolf, B. Braun Medical N.V., CODAN Medizinische Gerate GmbH &
      Co KG, Becton Dickinson and Company, and Terumo Europe. Adsorption of (99m)Tc
      DMSA(III) and (99m)Tc-nanocolloid was acceptably low for all syringes (<13%),
      except for two brands with (99m)Tc-DMSA(III) adsorption rates of 36 and 30%,
      respectively, and for one brand with a (99m)Tc-nanocolloid adsorption rate of
      27%. Adsorption of (99m)Tc-DMSA(III) and (99m)Tc-nanocolloid reaches critical
      levels in syringes produced by two brands, potentially causing poor image quality
      -for example, in DMSA scans using pediatric radiopharmaceutical doses. It is
      advised to check the compatibility of any radiopharmaceutical with syringes as an
      integral part of the quality assurance program.

PMID- 24569707
TI  - Annotation enrichment analysis: an alternative method for evaluating the
      functional properties of gene sets.
AB  - Gene annotation databases (compendiums maintained by the scientific community
      that describe the biological functions performed by individual genes) are
      commonly used to evaluate the functional properties of experimentally derived
      gene sets. Overlap statistics, such as Fishers Exact test (FET), are often
      employed to assess these associations, but don't account for non-uniformity in
      the number of genes annotated to individual functions or the number of functions
      associated with individual genes. We find FET is strongly biased toward over
      estimating overlap significance if a gene set has an unusually high number of
      annotations. To correct for these biases, we develop Annotation Enrichment
      Analysis (AEA), which properly accounts for the non-uniformity of annotations. We
      show that AEA is able to identify biologically meaningful functional enrichments
      that are obscured by numerous false-positive enrichment scores in FET, and we
      therefore suggest it be used to more accurately assess the biological properties
      of gene sets. 

PMID- 24569710
TI  - Gender discrimination is blamed for high rates of uterine prolapse in Nepal.

PMID- 24569709
TI  - IL-23 from Langerhans cells is required for the development of imiquimod-induced
      psoriasis-like dermatitis by induction of IL-17A-producing gammadelta T cells.
AB  - Psoriasis is a common chronic inflammatory skin disease that involves
      dysregulated interplay between immune cells and keratinocytes. Recently, it has
      been reported that IL-23 induces CCR6+ gammadelta T cells, which have the pivotal
      role in psoriasis-like skin inflammation in mice of producing IL-17A and IL-22.
      Langerhans cells (LCs) are a subset of dendritic cells that reside in the
      epidermis and regulate immune responses. The role of LCs has been extensively
      investigated in contact hypersensitivity, but their role in psoriasis remains to
      be clarified. In this study, we focused on Th17-related factors and assessed the
      role of LCs and gammadelta T cells in the development of psoriasis using a mouse
      psoriasis model triggered by topical application of imiquimod (IMQ). LC depletion
      by means of diphtheria toxin (DT) in Langerin DT receptor-knocked-in mice
      suppressed hyperkeratosis, parakeratosis, and ear swelling in the IMQ-treated
      regions. In addition, LC-depleted mice showed decreased levels of Th17-related
      cytokines in IMQ-treated skin lesions. Moreover, the IMQ-treated skin of LC
      depleted mice showed a decreased number of IL-17A-producing CCR6+ gammadelta T
      cells. These results suggest that LCs are required for the development of
      psoriasis-like lesions induced by IMQ in mice.

PMID- 24569713
TI  - Who deserves a place on the list of authors?

PMID- 24569711
TI  - Tumor targeting profiling of hyaluronan-coated lipid based-nanoparticles.
AB  - Hyaluronan (HA), a naturally occurring high Mw (HMw) glycosaminoglycan, has been
      shown to play crucial roles in cell growth, embryonic development, healing
      processes, inflammation, and tumor development and progression. Low Mw (LMw, <10
      kDa) HA has been reported to provoke inflammatory responses, such as induction of
      cytokines, chemokines, reactive nitrogen species and growth factors. Herein, we
      prepared and characterized two types of HA coated (LMw and HMw) lipid-based
      targeted and stabilized nanoparticles (tsNPs) and tested their binding to tumor
      cells expressing the HA receptor (CD44), systemic immunotoxicity, and
      biodistribution in tumor bearing mice. In vitro, the Mw of the surface anchored
      HA had a significant influence on the affinity towards CD44 on B16F10 murine
      melanoma cells. LMw HA-tsNPs exhibited weak binding, while binding of tsNPs
      coated with HMw HA was characterized by high binding. Both types of tsNPs had no
      measured effect on cytokine induction in vivo following intravenous
      administration to healthy C57BL/6 mice suggesting no immune activation. HMw HA
      tsNPs showed enhanced circulation time and tumor targeting specificity, mainly by
      accumulating in the tumor and its vicinity compared with LMw HA-tsNPs. Finally,
      we show that methotrexate (MTX), a drug commonly used in cancer chemotherapy,
      entrapped in HMw HA-tsNPs slowly diffused from the particles with a half-life of
      13.75 days, and improved the therapeutic outcome in a murine B16F10 melanoma
      model compared with NPs suggesting an active cellular targeting beyond the
      Enhanced Permeability and Retention (EPR) effect. Taken together, these findings
      have major implications for the use of high molecular weight HA in nanomedicine
      as a selective and safe active cellular targeting moiety. 

PMID- 24569714
TI  - Cancer screening after idiopathic venous thromboembolism?

PMID- 24569715
TI  - Is treatment of acute myocardial infarction in compliance with new guidelines?

PMID- 24569716
TI  - [This looks like a coup!].

PMID- 24569712
TI  - Loss of NDRG2 expression activates PI3K-AKT signalling via PTEN phosphorylation
      in ATLL and other cancers.
AB  - Constitutive phosphatidylinositol 3-kinase (PI3K)-AKT activation has a causal
      role in adult T-cell leukaemia-lymphoma (ATLL) and other cancers. ATLL cells do
      not harbour genetic alterations in PTEN and PI3KCA but express high levels of
      PTEN that is highly phosphorylated at its C-terminal tail. Here we report a
      mechanism for the N-myc downstream-regulated gene 2 (NDRG2)-dependent regulation
      of PTEN phosphatase activity via the dephosphorylation of PTEN at the Ser380,
      Thr382 and Thr383 cluster within the C-terminal tail. We show that NDRG2 is a
      PTEN-binding protein that recruits protein phosphatase 2A (PP2A) to PTEN. The
      expression of NDRG2 is frequently downregulated in ATLL, resulting in enhanced
      phosphorylation of PTEN at the Ser380/Thr382/Thr383 cluster and enhanced
      activation of the PI3K-AKT pathway. Given the high incidence of T-cell lymphoma
      and other cancers in NDRG2-deficient mice, PI3K-AKT activation via enhanced PTEN
      phosphorylation may be critical for the development of cancer. 

PMID- 24569717
TI  - [Poor title--poor manuscript?].

PMID- 24569718
TI  - [P. Gjersvik and colleagues reply].

PMID- 24569719
TI  - [Ovre Richter Frich and his models].

PMID- 24569720
TI  - [Bladder operations in Nordic history].

PMID- 24569721
TI  - [The legacy of a pioneer].

PMID- 24569722
TI  - [E. Sudmann and colleagues reply].

PMID- 24569723
TI  - [Retired surgeon, professor emeritus dr. med].

PMID- 24569725
TI  - [What's wrong with grades?].

PMID- 24569726
TI  - [Retract the articles].

PMID- 24569727
TI  - [C. Haug replies].

PMID- 24569728
TI  - [Inadequate correction of errors].

PMID- 24569732
TI  - [Prenatal diagnosis with blood tests].

PMID- 24569729
TI  - [C. Haug replies].

PMID- 24569733
TI  - [Aphasia--when the system fails just as much as the language].

PMID- 24569734
TI  - [Does silibinin have a place in the treatment of liver diseases?].

PMID- 24569735
TI  - [Electromagnetic fields in medicine--need for risk assessment?].

PMID- 24569736
TI  - [Excessive belief in suicide risk assessments?].

PMID- 24569739
TI  - Limited malignancy screening of patients with idiopathic venous thromboembolism.
AB  - BACKGROUND: There is a known relationship between venous thromboembolism and
      cancer, but there is no consensus as to how extensive screening for occult cancer
      should be in cases of venous thromboembolism with no apparent risk factor
      (idiopathic venous thromboembolism). The aim of this study was to investigate the
      extent to which limited screening of patients with idiopathic venous
      thromboembolism reveals occult cancer. MATERIAL AND METHOD: The incidence of
      cancer during the first year after thrombosis was surveyed retrospectively for
      all patients with idiopathic venous thromboembolism at Baerum Hospital in the
      period 1.1. 2003-31.12. 2008. During this period, limited malignancy screening
      was performed routinely in cases of idiopathic venous thromboembolism, and we
      investigated the degree to which limited screening had indicated the possible
      presence of cancer. RESULTS: Of 974 patients with venous thromboembolism, 499 had
      idiopathic venous thromboembolism. Malignancy was detected in 47 of these (9.4%;
      95% CI 7.1-12.3) during the first year after the thrombosis. Limited screening
      detected 44 of these 47 cases (94%) and had a negative predictive value of 99%.
      Limited screening found anomalies in 98 patients (20%) in whom malignancy was not
      detected. INTERPRETATION: Malignancy was detected in almost 10% of the patients
      with idiopathic venous thromboembolism in the course of the first year. Limited
      screening for occult malignancy identified the great majority of cases.

PMID- 24569740
TI  - Are the guidelines for treatment of myocardial infarction complied with?
AB  - BACKGROUND: New guidelines recommend early invasive evaluation and treatment for
      most patients with acute myocardial infarction--including patients with
      myocardial infarction without ST elevation in the ECG. This study examines
      compliance with the new guidelines at Sorlandet Hospital Arendal. MATERIAL AND
      METHOD: All patients admitted to Sorlandet Hospital Arendal with acute myocardial
      infarction in 2012 were registered in the Norwegian Myocardial Infarction
      Register. Data from the register were used to analyse the time that passed from
      symptom onset to coronary angiography and revascularisation. RESULTS: In 2012,
      788 patients were admitted to Sorlandet Hospital Arendal with acute myocardial
      infarction. Of these, 269 (34.1%) had ST elevation mycardial infarction (STEMI)
      and 519 (65.9%) had non-ST elevation myocardial infarction (NSTEMI). Most
      patients with ST elevation infarction (220 (81.8%)) were admitted directly to
      Sorlandet Hospital Arendal, and the median time from admission to
      revascularisation was 31 minutes. 347 (66.9%) of the patients with non-ST
      elevation infarction were first admitted to a local hospital before being
      transferred to Sorlandet Hospital Arendal. Only four (1.2%) of them underwent
      angiography within two hours of admission to the first hospital. 13 (9.0%) of the
      patients with non-ST elevation infarction who were admitted directly and
      underwent angiography (n = 144) had an angiogram within two hours of admission.
      Angiography was performed within 24 hours in 119 (34.3%) of those transferred (n
      = 347) and in 82 (56.9%) of the directly admitted patients who underwent
      angiography (n = 144). INTERPRETATION: Many patients with non-ST elevation
      infarction did not receive revascularisation with percutaneous coronary
      intervention (PCI) within the recommended time frame. Where there is a strong
      clinical suspicion of acute myocardial infarction, more patients should be
      admitted directly to hospitals with PCI preparedness.

PMID- 24569741
TI  - [Sources of error when using haemoglobin A1c].
AB  - BACKGROUND: Measurement of glycated haemoglobin A1 in whole blood (b-HbA1c) can
      be used in both diagnosing and following up patients with diabetes. Correct
      interpretation of analytical results is contingent on agreement between average
      plasma glucose (p-glucose) and b-HbA1c. This article provides an overview of
      factors that may result in a discrepancy between average glucose concentration
      and b-HbA1c. METHOD: Literature search in PubMed to identify scientific articles
      that describe strengths and weaknesses of b-HbA1c. RESULTS: The b-HbA1c reading
      usually provides a good picture of average p-glucose for the preceding two to
      three months. Patients who are being treated with iron/vitamin B12 supplements,
      have liver failure, haemolytic anaemia or bleeding usually have a lower b-HbA1c
      than their p-glucose level would suggest. With increasing patient age, B12
      deficiency or iron deficiency anaemia, higher values of b-HbA1c are seen for the
      same p-glucose level. Some ethnic groups have a higher b-HbA1c than their average
      p-glucose would suggest, but the risk of long-term complications appears
      generally to be more closely associated with b-HbA1c than with the glucose level.
      Pregnancy, renal failure or haemoglobinopathies may make the b-HbA1c value
      unreliable as an expression of average p-glucose. INTERPRETATION: Correct
      interpretation of b-HbA1c is conditional on the requisitioner being aware of
      possible sources of error. If the patient is suspected to have a condition that
      leads to lack of consistency between b-HbA1c and average p-glucose, glucose-based
      criteria must be used in diagnosing diabetes.

PMID- 24569742
TI  - [Child with crooked legs].

PMID- 24569743
TI  - [Woman in her 30s with chronic fatigue].

PMID- 24569744
TI  - [A pregnant woman with vomiting and breathing difficulties].

PMID- 24569745
TI  - [Not "just" morning sickness].

PMID- 24569746
TI  - Structured electronic health records.
AB  - In order to succeed in realising general health-policy goals for cancer care,
      they must be formulated as specific and realistic objectives. An administrative
      organ must be provided with the authority and funding needed to establish the
      technical solutions required. Reporting to national registries must take place
      automatically in electronic form, on the basis of ongoing structured reporting in
      the patient records. In our opinion the Directorate of Health should enter into
      cooperation with the College of American Pathologists, with a view to integrating
      a Norwegian version of their electronic checklists for pathology reporting of
      cancer into the hospitals' record systems.

PMID- 24569747
TI  - [Touch anxiety].

PMID- 24569748
TI  - [Physicians' private referral practices].

PMID- 24569752
TI  - Synergistic recombination suppression by an inorganic layer and organic dye
      molecules in highly photostable quantum dot sensitized solar cells.
AB  - An inorganic layer and dye molecules have synergistically suppressed the
      recombination in a quantum dot sensitized solar cell (QDSSC), by the design of a
      structure featured TiO2-CdS-ZnS-N3 (N3: RuL2(NCS)2 (L = 2,2'-bipyridyl-4,4'
      dicarboxylic acid)) hybrid photoanode. When fabricated into solar cells, a cobalt
      complex-based electrolyte rather than an iodine-based one was employed to obtain
      an impressive photostability for the devices. Raman and Photoluminescence (PL)
      measurements revealed that not only the CdS QDs were passivated by both the
      inorganic layer of ZnS and dye molecule of N3, but also N3 served as an efficient
      hole scavenger for the CdS QDs due to a type-II energetic alignment between the
      two sensitizers. This role of N3 as an intermediary in hole extraction from CdS
      QDs to the electrolyte was further proven by the significant photovoltaic
      performance improvement of the CdS sensitized solar cell after ZnS deposition and
      N3 co-sensitization. The overall efficiency of the solar cell incorporated with
      TiO2-CdS-ZnS-N3 film exceeded the sum of the single CdS QDs and N3 dye sensitized
      solar cells. This enhancement is ascribed mainly to the synergistic recombination
      suppression by the inorganic layer ZnS and N3 co-sensitization, leading to
      inhibited recombination and increased electron lifetime, as illustrated by the
      electrochemical impedance spectroscopy (EIS) analysis. 

PMID- 24569753
TI  - Civilian health care systems have been involved in population care, too.

PMID- 24569755
TI  - Interview.

PMID- 24569754
TI  - Population health management.

PMID- 24569757
TI  - Preparing the emerging nursing and health care workforce: a case study.
AB  - How do we prepare the nursing and health workforce of the future to meet the
      challenges of the US health system and equip graduates with problem-solving
      strategies that are scientific, compassionate, and agile? This article provides
      examples of several approaches for nursing health professions education,
      including innovation, interprofessionalism, and multiple, simultaneous community
      collaboratives. Specific examples highlight ways academic nursing programs and
      practice organizations are working together to provide stimulating, realistic,
      safe, and effective education while exposing students to the challenges inherent
      in the health system. 

PMID- 24569756
TI  - Getting past widgets and digits: the fundamental transformation of the
      foundations of nursing practice.
AB  - Health reform and transformation now call for the creation of a new landscape for
      nursing practice based on intentional translation application of value-driven
      measures of service, quality, and price. Nursing is a central driver in the
      effective recalibration of health care within the rubric of health transformation
      under the aegis of the Patient Protection and Affordable Care Act. Increasingly
      relying on a growing digital infrastructure, the nursing profession must now
      reframe both its practice foundations and patterns of practice to reflect
      emerging value-driven, health-grounded service requisites. Specific nursing
      responses are suggested, which position nursing to best coordinate, integrate,
      and facilitate health delivery in the emerging value-driven service environment. 

PMID- 24569758
TI  - Meeting new health care challenges with a proven innovation: nurse-managed health
      care clinics.
AB  - Beginning in January 2014, millions of Americans will enroll in health insurance
      plans under the Affordable Care Act. Some of these individuals were obtaining
      health care in safety net health clinics, emergency departments, or urgent care
      centers; many were going without needed care and will be new to the health care
      system. In addition to these newly insured, the ranks of older Americans and
      persons in need of chronic disease management will be on the rise. The way in
      which health care is delivered will have to change in order for the health care
      workforce to meet the demand for their services without sacrificing quality or
      access. Nurse practitioners and registered nurses have the education and skills
      to provide health promotion, disease prevention, and chronic disease management
      services that will make up a sizable portion of the demand. Amending state
      practice acts so that the authority to practice matches the ability to practice
      and opening provider panels to advanced practice nurses will provide
      opportunities to establish or expand sustainable nurse-led primary care practices
      in health care shortage areas. Along with these changes, models of health care
      delivery that incorporate differentiated practice roles and shared
      interprofessional responsibility for providing care will maximize the capacity of
      the system to provide the health care that people need. 

PMID- 24569759
TI  - Embarking on accountable care: preparing for the second curve.
AB  - With the advent of the Affordable Care Act, new models of care are underway.
      Health care experts agree that to improve care, there will need to be improved
      partnerships across the care continuum, finally eliminating silos of care and
      services. WellStar Health System, a large health care system in the southeastern
      part of the United States, is demonstrating its early adoption of integration and
      the new rules of engagement. These rules will fundamentally change the course of
      how to provide health care and lead the way for a more accountable-based model of
      care delivery. This article describes the anticipated and successful preliminary
      outcomes achieved in the first year of this system's demonstration project in the
      Medicare Shared Savings Program or "Medicare ACO." WellStar Health System began
      with a focus on addressing the needs of the heart failure patient. In an effort
      to achieve the triple aim of improving access, reducing cost, and improving
      outcomes, the system designed a dedicated inpatient heart failure unit. This unit
      operates with a new and sustainable structure that actually links the
      interdisciplinary and multiple providers of care across the care continuum. In
      doing so, a significant improvement in achieving patient's compliance with care
      treatment and a reduction in hospital readmissions have been achieved. 

PMID- 24569760
TI  - A national system approach to oncology patient population management across the
      continuum of care: how we standardized navigation.
AB  - The increasing complexity of cancer care has the potential to result in care
      fragmentation and suboptimal coordination and timeliness to care. In managing the
      oncology patient population, navigators have the opportunity to provide patient
      centered care throughout the cancer care trajectory and to positively impact
      patient's outcomes. The role of the navigator benefits both the patient and the
      cancer care team by fostering continuity of care and improved communication. As
      cancer programs find themselves struggling with the global challenges that
      surround the evolution of patient's navigation and seeking to provide evidence
      based care, Catholic Health Initiatives' National Oncology Service Line developed
      a system-wide approach to identifying and deploying best practices for navigation
      across their cancer programs. 

PMID- 24569761
TI  - Nursing and the science of prevention for population health.
AB  - The topic of patient-centered care is at the very epicenter of the contemporary
      emphasis on a value-based approach to health care. Multiple studies confirm that
      positive outcomes are consistently achieved when clinicians and administrators
      put appropriate emphasis on patient-centered care. Although we would agree that
      the patient-centered approach is necessary for achieving positive clinical
      outcomes for individual patients, we suggest that this approach alone is
      insufficient to sustain these outcomes across large populations over an extended
      period of time. We believe that a science-based approach to population health
      coupled with patient-centered care pathways will achieve the most effective, long
      term impact for large groups of individuals. Furthermore, we believe that nurses
      play a central role in a science-based approach to patient-centered medical care.
      In this article, we discuss the intersection of preventative science, patient
      centered care, and the role of nurses. We present our experience at Texas Health
      Resources with the use of clinical nurse leaders in a science-based population
      health approach to achieve more consistent, positive outcomes during transition
      of care. Finally, we suggest that care providers integrate the science of
      prevention with the principles of patient-centered care to more consistently
      deliver on the promise of population health. 

PMID- 24569762
TI  - Building on a legacy for the era of population health.
AB  - The 2011 Joplin tornado was a catastrophic EF5 multiple-vortex tornado that
      struck Joplin, Missouri, late in the afternoon of Sunday, May 22, 2011. It was
      part of a larger, late-May tornado outbreak and reached a maximum width of nearly
      1 mile (1.6 km) during its path through the city. Mercy St John's Hospital (which
      had recently joined Mercy Ministries) suffered a direct hit and was rendered
      nonuseable. A total of 183 patients and nearly 200 coworkers/staff members were
      evacuated from the building within the next 90 minutes. Triage centers were set
      up outside as hospitals of other areas opened their doors for St John's patients
      and community members who had been injured. The tornado in Joplin destroyed Mercy
      St John's Hospital. Given this future, why did Mercy Ministries choose to rebuild
      an acute care facility rather than merely an outpatient system? The organization
      considered current community needs and the needs of the future. They also
      remembered their mission and the legacy of their heritage. 

PMID- 24569763
TI  - Five key pillars of an analytics center of excellence, which are required to
      manage populations and transform organizations into the next era of health care.
AB  - Acute care facilities are experiencing fiscal challenges as noted by decreasing
      admissions and lower reimbursement creating an unsustainable fiscal environment
      as we move into the next era of health care. This situation necessitates a
      strategy to move away from acting solely on hunches and instinct to using
      analytics to become a truly data-driven organization that identifies
      opportunities within patient populations to improve the quality and efficiency of
      care across the continuum. A brief overview of knowledge management philosophies
      will be provided and how it is used to enable organizations to leverage data,
      information, and knowledge for operational transformation leading to improved
      outcomes. This article outlines the 5 key pillars of an Analytics Center of
      Excellence; governance, organizational structure, people, process, and
      technology, that are foundational to the development of this strategy. While
      culture is the most important factor to achieve organizational transformation and
      improved care delivery, it is the 5 pillars of the ACoE that will enable the
      culture shift necessary to become a truly data-driven organization and thus
      achieve transformation into the next era of health care. 

PMID- 24569764
TI  - Bringing care home: how telemonitoring can expand population health management
      beyond the hospital.
AB  - With emerging technology, patients are able to access the health care system from
      settings such as their homes, long-term care facilities, and schools.
      Telemonitoring allows care teams to oversee patients' clinical data captured and
      transmitted by specialized devices, with minimal involvement or manual effort, on
      a near real-time basis. This review was undertaken to provide insight into the
      capacity of telemonitoring technology to improve population health. Despite the
      potential of telemonitoring, evidence for its clinical, economic, and patient
      reported benefits is inconclusive. Much of the outcome variation seen in the
      literature may be due to the heterogeneity of the interventions' characteristics,
      with some telemonitoring programs more effectively integrating into standard
      practice, targeting patients, and utilizing technology. A particular challenge is
      the ability to comprehensively leverage data to improve health outcomes. To
      accomplish this, the mass data collected by the devices must be aggregated with
      data from other clinical systems and used to develop predictive algorithms that
      can be embedded across the continuum of care. Innovations such as the Healthe
      Intent cloud-based platform can support a population health strategy by
      integrating telemonitoring and electronic health record data. 

PMID- 24569765
TI  - Aging patients: nursing implications for direct care nurses.
AB  - Experience with my mother over the past 3 years led me reflect on how we care for
      older adults. For those who do not have a nurse in the family to provide care
      coordination and oversight, how are the gaps in continuity of care and
      transitions in care addressed? Many specialized positions are emerging for nurses
      in care coordination. These positions tend to focus on the most complex patients
      and on selected transitions in care. There are pockets of excellence but nurses
      who provide direct care in inpatient and outpatient settings are the safety net
      for older adults like my mother. They need competencies in assessment of older
      adults and awareness of how illness may present differently in this population.
      They need to be aware of the entire continuum of care and provide care
      coordination for patients who are not receiving specialized care coordination
      services. 

PMID- 24569766
TI  - It takes a village: a community partnership model in caring for the homeless.
AB  - Population health management calls for hospitals and health care entities to
      better align their strategies in order to deliver quality care more efficiently.
      Although these efforts tend to be addressed with insured populations, the
      homeless demand a very intentional focus. The issue of homelessness has adverse
      effects on the health care system, resulting in the inefficient use of resources.
      Community-wide efforts must be mobilized to address this inefficiency and need
      for preventative care and self-management education for this population.
      Carondelet Health Network, in partnership with El Rio Community Health Center, a
      federally qualified health center, along with other health care and social
      service providers, has established the Southern Arizona Health Village for the
      Homeless, providing a health care delivery system to ensure the best functional
      and clinical outcomes. This system includes a van (the Van of Hope), licensed as
      a health center, and staffed with an El Rio Community Health Center nurse
      practitioner and a medical assistant partnering with a Carondelet Health Network
      behavioral health specialist and a community outreach worker. Clinical patient
      information is managed via an electronic health record inclusive of clinical
      data, number of visits, referrals, self-management education, hospitalizations,
      and follow-up care. A post-hospital program with shelters and an Emergency Room
      Navigation Program are additional components of the village that provide a
      comprehensive pre-acute and post-acute effort to support the homeless. Financial
      impact is measured by reductions in hospitalizations and average length of stay. 

PMID- 24569767
TI  - Nursing education focus of nursing informatics research in 2013.
AB  - The Nursing Informatics Year in Review 2013 revealed an increase in publications
      associated with nursing education. Specifically, the articles addressed
      technology in nursing curricula, use of technology to teach nursing education,
      and use of technology to form collaborative relationships. In this article we
      present questions such as: how do these programs assist student nurses to
      transition to nurse providers where technology is infused into their work and
      workflow and what is the influence of the collaborative relationships with nurse
      educators, administrators, and informatics specialists increase patient safety
      and quality. 

PMID- 24569768
TI  - Views on scope of practice: is it time for a continuum-based population-driven
      model?

PMID- 24569771
TI  - The spillover effects of focused deterrence on gang violence.
AB  - BACKGROUND: Focused deterrence strategies attempt to increase punishment risks
      faced by violent gangs through the development of new and creative ways of
      deploying traditional and non-traditional law enforcement tools. In addition to
      increasing the swiftness and certainty of sanctions, these strategies explicitly
      communicate incentives and disincentives to deter likely gang offenders from
      violent behavior. OBJECTIVE: This study seeks to determine whether focused
      deterrence strategies generate spillover deterrent effects on the gun violence
      behaviors of vicariously treated gangs that were socially tied to directly
      treated violent gangs. RESEARCH DESIGN: A nonrandomized quasi-experimental design
      was used to evaluate the gun violence reduction effects of focused deterrence
      strategies on directly treated gangs and vicariously treated gangs. Propensity
      score matching techniques were used to identify balanced comparison gangs for the
      vicariously treated gangs. Growth curve regression models were used to analyze
      gun violence trends for treated gangs relative to comparison gangs. UNIT OF
      ANALYSIS: Quarterly counts of fatal and non-fatal shootings involving specific
      street gangs between 2006 and 2010 served as the units of analysis. MEASURES: Key
      outcome measures included quarterly shootings committed by specific gangs,
      shooting victimizations suffered by specific gangs, and the total number of
      shootings involving specific gangs. RESULTS: The focused deterrence strategy was
      associated with statistically significant reductions in total shootings by
      directly treated gangs and vicariously treated gangs. CONCLUSIONS: Our study
      finds that vicariously treated gangs were deterred by the treatment experiences
      of their rivals and allies. This suggests that focused deterrence strategies can
      generate spillover crime reduction effects to gangs that are socially connected
      to directly treated gangs.

PMID- 24569770
TI  - SnRK1A-interacting negative regulators modulate the nutrient starvation signaling
      sensor SnRK1 in source-sink communication in cereal seedlings under abiotic
      stress.
AB  - In plants, source-sink communication plays a pivotal role in crop productivity,
      yet the underlying regulatory mechanisms are largely unknown. The SnRK1A protein
      kinase and transcription factor MYBS1 regulate the sugar starvation signaling
      pathway during seedling growth in cereals. Here, we identified plant-specific
      SnRK1A-interacting negative regulators (SKINs). SKINs antagonize the function of
      SnRK1A, and the highly conserved GKSKSF domain is essential for SKINs to function
      as repressors. Overexpression of SKINs inhibits the expression of MYBS1 and
      hydrolases essential for mobilization of nutrient reserves in the endosperm,
      leading to inhibition of seedling growth. The expression of SKINs is highly
      inducible by drought and moderately by various stresses, which is likely related
      to the abscisic acid (ABA)-mediated repression of SnRK1A under stress.
      Overexpression of SKINs enhances ABA sensitivity for inhibition of seedling
      growth. ABA promotes the interaction between SnRK1A and SKINs and shifts the
      localization of SKINs from the nucleus to the cytoplasm, where it binds SnRK1A
      and prevents SnRK1A and MYBS1 from entering the nucleus. Our findings demonstrate
      that SnRK1A plays a key role regulating source-sink communication during seedling
      growth. Under abiotic stress, SKINs antagonize the function of SnRK1A, which is
      likely a key factor restricting seedling vigor.

PMID- 24569772
TI  - A disposable alkaline phosphatase-based biosensor for vanadium chronoamperometric
      determination.
AB  - A chronoamperometric method for vanadium ion determination, based on the
      inhibition of the enzyme alkaline phosphatase, is reported. Screen-printed carbon
      electrodes modified with gold nanoparticles were used as transducers for the
      immobilization of the enzyme. The enzymatic activity over 4-nitrophenyl phosphate
      sodium salt is affected by vanadium ions, which results in a decrease in the
      chronoamperometric current registered. The developed method has a detection limit
      of 0.39 +/- 0.06 uM, a repeatability of 7.7% (n = 4) and a reproducibility of 8%
      (n = 3). A study of the possible interferences shows that the presence of Mo(VI),
      Cr(III), Ca(II) and W(VI), may affect vanadium determination at concentration
      higher than 1.0 mM. The method was successfully applied to the determination of
      vanadium in spiked tap water. 

PMID- 24569773
TI  - Implementation and performance of a GPS/INS tightly coupled assisted PLL
      architecture using MEMS inertial sensors.
AB  - The use of global navigation satellite system receivers for navigation still
      presents many challenges in urban canyon and indoor environments, where satellite
      availability is typically reduced and received signals are attenuated. To improve
      the navigation performance in such environments, several enhancement methods can
      be implemented. For instance, external aid provided through coupling with other
      sensors has proven to contribute substantially to enhancing navigation
      performance and robustness. Within this context, coupling a very simple GPS
      receiver with an Inertial Navigation System (INS) based on low-cost micro-electro
      mechanical systems (MEMS) inertial sensors is considered in this paper. In
      particular, we propose a GPS/INS Tightly Coupled Assisted PLL (TCAPLL)
      architecture, and present most of the associated challenges that need to be
      addressed when dealing with very-low-performance MEMS inertial sensors. In
      addition, we propose a data monitoring system in charge of checking the quality
      of the measurement flow in the architecture. The implementation of the TCAPLL is
      discussed in detail, and its performance under different scenarios is assessed.
      Finally, the architecture is evaluated through a test campaign using a vehicle
      that is driven in urban environments, with the purpose of highlighting the pros
      and cons of combining MEMS inertial sensors with GPS over GPS alone. 

PMID- 24569769
TI  - A pollen coat-inducible autoinhibited Ca2+-ATPase expressed in stigmatic papilla
      cells is required for compatible pollination in the Brassicaceae.
AB  - In the Brassicaceae, intraspecific non-self pollen (compatible pollen) can
      germinate and grow into stigmatic papilla cells, while self-pollen or
      interspecific pollen is rejected at this stage. However, the mechanisms
      underlying this selective acceptance of compatible pollen remain unclear. Here,
      using a cell-impermeant calcium indicator, we showed that the compatible pollen
      coat contains signaling molecules that stimulate Ca(2+) export from the papilla
      cells. Transcriptome analyses of stigmas suggested that autoinhibited Ca(2+)
      ATPase13 (ACA13) was induced after both compatible pollination and compatible
      pollen coat treatment. A complementation test using a yeast Saccharomyces
      cerevisiae strain lacking major Ca(2+) transport systems suggested that ACA13
      indeed functions as an autoinhibited Ca(2+) transporter. ACA13 transcription
      increased in papilla cells and in transmitting tracts after pollination. ACA13
      protein localized to the plasma membrane and to vesicles near the Golgi body and
      accumulated at the pollen tube penetration site after pollination. The stigma of
      a T-DNA insertion line of ACA13 exhibited reduced Ca(2+) export, as well as
      defects in compatible pollen germination and seed production. These findings
      suggest that stigmatic ACA13 functions in the export of Ca(2+) to the compatible
      pollen tube, which promotes successful fertilization.

PMID- 24569775
TI  - The role of PAX5 and C/EBP alpha/beta in atypical non-Langerhans cell histiocytic
      tumor post acute lymphoblastic leukemia.

PMID- 24569776
TI  - A multi-centre phase 2 study of azacitidine in chronic myelomonocytic leukaemia.

PMID- 24569777
TI  - JAK inhibition with ruxolitinib as pretreatment for allogeneic stem cell
      transplantation in primary or post-ET/PV myelofibrosis.

PMID- 24569778
TI  - Type 1 vs type 2 calreticulin mutations in primary myelofibrosis: differences in
      phenotype and prognostic impact.

PMID- 24569781
TI  - Anaesthesia for orphan disease: Haddad syndrome (Ondine-Hirschsprung disease).

PMID- 24569786
TI  - Microsatellite instability confounds engraftment analysis of hematopoietic stem
      cell transplantation.
AB  - Polymorphic short tandem-repeat, or microsatellite, loci have been widely used to
      analyze chimerism status after allogeneic hematopoietic stem-cell
      transplantation. In molecular diagnostic laboratories, it is recommended to
      calculate mixed chimerism for at least 2 informative loci and to avoid
      microsatellite loci on chromosomes with copy number changes. In this report, we
      show that microsatellite instability observed in 2 patients with acute leukemia
      may confound chimerism analysis. Interpretation errors may occur even if 2 to 3
      loci are analyzed because of length variation in multiple microsatellite loci.
      Although microsatellite loci with length variation should not be selected for
      chimerism analysis, the presence of microsatellite instability, like copy number
      alteration because of aberrant chromosomes, provides evidence of recurrent or
      residual cancer cells after hematopoietic stem-cell transplantation.

PMID- 24569779
TI  - TGF-beta upregulates CD70 expression and induces exhaustion of effector memory T
      cells in B-cell non-Hodgkin's lymphoma.
AB  - Transforming growth factor beta (TGF-beta) has an important role in mediating T
      cell suppression in B-cell non-Hodgkin lymphoma (NHL). However, the underlying
      mechanism responsible for TGF-beta-mediated inhibition of effector memory T (Tm)
      cells is largely unknown. As reported here, we show that exhaustion is a major
      mechanism by which TGF-beta inhibits Tm cells, and TGF-beta mediated exhaustion
      is associated with upregulation of CD70. We found that TGF-beta upregulates CD70
      expression on effector Tm cells while it preferentially induces Foxp3 expression
      in naive T cells. CD70 induction by TGF-beta is Smad3-dependent and involves IL
      2/Stat5 signaling. CD70+ T cells account for TGF-beta-induced exhaustion of
      effector Tm cells. Both TGF-beta-induced and preexisting intratumoral CD70+
      effector Tm cells from B-cell NHL have an exhausted phenotype and express higher
      levels of PD-1 and TIM-3 compared with CD70- T cells. Signaling transduction,
      proliferation and cytokine production are profoundly decreased in these cells,
      and they are highly susceptible to apoptosis. Clinically, intratumoral CD70
      expressing T cells are prevalent in follicular B-cell lymphoma (FL) biopsy
      specimens, and increased numbers of intratumoral CD70+ T cells correlate with an
      inferior patient outcome. These findings confirm TGF-beta-mediated effector Tm
      cell exhaustion as an important mechanism of immune suppression in B-cell NHL.

PMID- 24569788
TI  - A new rabbit monoclonal E-cadherin antibody [EP700Y] shows higher sensitivity
      than mouse monoclonal E-cadherin [HECD-1] antibody in breast ductal carcinomas
      and does not stain breast lobular carcinomas.
AB  - Immunohistochemical studies have shown E-cadherin to be expressed in breast
      carcinomas showing a ductal histology, with a corresponding loss of expression in
      tumors with a lobular histology. As a result, mouse monoclonal anti-E-cadherin
      [HECD-1] has been used by pathologists to differentiate between ductal and
      lobular carcinomas, with currently published sensitivity and specificity rates of
      approximately 90%. Rabbit monoclonal antibodies may combine the best properties
      of both mouse monoclonal antibodies and rabbit antisera. Therefore, this study
      compares the staining sensitivity and specificity of a new rabbit monoclonal E
      cadherin and the standard mouse monoclonal E-cadherin [HECD-1] in breast ductal
      carcinomas, and evaluates a cocktail of rabbit monoclonal E-cadherin and p120
      catenin in the discrimination of ductal from lobular carcinomas. The rabbit E
      cadherin showed sharper staining and increased sensitivity (80/81, 99%) than the
      mouse E-cadherin (75/81, 93%). The rabbit E-cadherin achieved a score of 3+ in
      85.2% (69/81) of cases as compared with a 3+ in only 21.0% (17/81) of cases
      stained with mouse E-cadherin. All lobular carcinomas (n=37) were confirmed by
      the absence of E-cadherin and the diffuse cytoplasmic expression of p120 catenin.
      Although both the single mouse E-cadherin and dual stain can differentiate ductal
      from lobular lesions, the dual stain is helpful in challenging cases because of
      its bright pink p120 catenin and dark brown rabbit E-cadherin staining. The
      highly sensitive rabbit E-cadherin antibody is the preferred antibody for
      evaluating ductal carcinomas and for distinguishing ductal versus lobular
      lesions, and the dual stain was superior to the single E-cadherin stain. 

PMID- 24569789
TI  - Finalists are announced for The BMJ Awards 2014.

PMID- 24569791
TI  - Evaluation of parenteral nutrition-associated liver disease in infants with
      necrotizing enterocolitis before and after the implementation of feeding
      guidelines.
AB  - BACKGROUND: In 2009, an intestinal rehabilitation team implemented feeding
      guidelines for infants following gastrointestinal surgery at our institution. The
      purpose of this study was to determine the effect of enteral feeding guidelines
      on the incidence of parenteral nutrition (PN)-associated liver disease (PNALD) in
      infants with surgically managed necrotizing enterocolitis (NEC). METHODS: This
      retrospective study included infants treated during 18-month time periods before
      and after the implementation of feeding guidelines. PNALD diagnosis was based on
      serum direct bilirubin >2 mg/dL after >=14 days of PN exposure. RESULTS: Of the
      140 infants identified, 64 were surgically managed and included in the analysis.
      The duration of PN and the time nil per os (NPO) were significantly reduced after
      guideline implementation from a median of 106 days to 65 days (P = .03) and from
      29 days to 16 days (P = .02), respectively. The incidence of PNALD decreased from
      73% before guideline implementation to 42% after guideline implementation (P =
      .01). CONCLUSIONS: Implementation of feeding guidelines resulted in decreased
      time NPO and duration of PN support. Significantly fewer infants developed PNALD
      after guideline implementation. These data suggest that feeding guidelines may
      expedite the transition from PN to enteral nutrition and may improve outcomes.

PMID- 24569790
TI  - Telomerase reverse transcriptase promoter mutations in primary cutaneous
      melanoma.
AB  - We previously reported a disease segregating causal germline mutation in a
      melanoma family and recurrent somatic mutations in metastasized tumours from
      unrelated patients in the core promoter region of the telomerase reverse
      transcriptase (TERT) gene. Here we show that the TERT promoter mutations, besides
      causing an increased gene expression, associate with increased patient age,
      increased Breslow thickness and tumour ulceration in 287 primary melanomas. The
      mutations are more frequent at both intermittently and chronically sun-exposed
      sites than non-exposed sites and tend to co-occur with BRAF and CDKN2A
      alterations. The association with parameters generally connected with poor
      outcome, coupled with high recurrence and mechanistic relevance, raises the
      possibility of the eventual use of TERT promoter mutations in the disease
      management. 

PMID- 24569792
TI  - How hyperalimentation may be necessary to reverse severe malnutrition in selected
      patients receiving home parenteral nutrition.
AB  - Standard predictive equations may under- or overestimate caloric requirements in
      disease states such as obesity or in patients with a low body mass index (BMI).
      Although this principle is common knowledge among nutrition specialists, it is
      often not prioritized with other clinicians outside the intensive care unit
      (ICU). Indirect calorimetry (IC) is often used in the ICU to estimate caloric
      requirements. This article outlines a very complicated case of a cachectic man
      with an enterocutaneous fistula who had lost more than 50% of body weight over 2
      years. In rehabilitating this patient, we found that the most common formulas of
      basal needs greatly underestimated the calories required to prepare him for
      restorative surgery. Key learning points are that in malnourished ambulatory
      patients, predictive equations may not adequately estimate caloric needs and IC
      may be required. 

PMID- 24569793
TI  - Wavelet analysis of lunar semidiurnal tidal influence on selected inland rivers
      across the globe.
AB  - The lunar semidiurnal influence is already known for tidal rivers. The moon also
      influences inland rivers at a monthly scale through precipitation. We show that,
      for some non-tidal rivers, with special geological conditions, the lunar
      semidiurnal tidal oscillation can be detected. The moon has semidiurnal tidal
      influence on groundwater, which will then export it to streamflow. Long time
      series with high frequency measurements were analysed by using standard wavelet
      analysis techniques. The lunar semidiurnal signal explains the daily double
      peaked river level evolution of inland gauges. It is stronger where springs with
      high discharge occur, especially in the area of Edwards-Trinity and Great
      Artesian Basin aquifers and in areas with dolomite/limestone strata. The average
      maximum semidiurnal peaks range between 0.002 and 0.1 m. This secondary effect of
      the earth tides has important implications in predicting high resolution
      hydrographs, in the water cycle of wetlands and in water management.

PMID- 24569795
TI  - Atraumaticity study of 2 cochlear implant electrode arrays.
AB  - HYPOTHESIS: Evaluate, based on morphologic and histologic parameters, the
      atraumaticity of 2 electrode arrays implanted in 10 human temporal bones.
      BACKGROUND: Atraumatic surgery and electrode arrays are current topics in
      otologic surgery. The preservation of cochlear anatomy and its functions is a
      priority and morphologic evaluation of the surgical trauma is essential to
      continue improving in this field. METHODS: Ten preserved human temporal bones
      (TB) without anatomic alterations were used in this study. They were divided into
      2 groups of 5, and atraumatic surgery was performed to insert HiFocus 1J (group
      A) and HiFocus Helix (group B) electrode arrays. Anatomic comparisons were
      performed using computed tomography and histologic analysis. RESULTS: Group A:
      the mean length for the cochlear longitudinal axis was 10.30 mm, and the cochlear
      transversal axis was 7.2 mm. Scala tympani insertion was achieved in 4/5 TB
      studied, with a mean depth and angle of insertion of 19.2 mm and 325.5 degrees ,
      respectively. Lateral location of the electrode array was achieved in all
      specimens. No significant correlation was observed between these dimensions and
      depth of insertion. Group B: the mean length for the cochlear longitudinal axis
      was 9.52 mm, and cochlear transversal axis was 6.38 mm. Scala tympani insertion
      was achieved in 4/5 TB studied, with a mean depth and angle of insertion of 17.5
      mm and 352 degrees , respectively. Modiolar location of the electrode array was
      achieved in all specimens. A positive correlation was established between the
      linear and angular insertion depths (p = 0.044). CONCLUSION: In summary, it is
      safe to state that neither electrode array shows significant insertion trauma.

PMID- 24569794
TI  - Comparison of stapedotomy minus prosthesis, circumferential stapes mobilization,
      and small fenestra stapedotomy for stapes fixation.
AB  - OBJECTIVE: To compare the outcomes of 3 surgical techniques for primary stapes
      fixation: stapedotomy minus prosthesis (STAMP), circumferential stapes
      mobilization (CSM), and small fenestra stapedotomy (SFS). STUDY DESIGN:
      Retrospective review of 277 primary cases operated for stapes fixation from 1997
      to 2007. SETTING: Tertiary academic center. PATIENTS: Consecutive adult and
      pediatric cases operated for conductive hearing loss because of stapes fixation.
      INTERVENTIONS: STAMP was performed for otosclerosis limited to the anterior
      footplate, CSM was conducted for congenital stapes fixation, SFS was performed
      for more extensive otosclerosis or anatomic contraindications to STAMP/CSM. MAIN
      OUTCOME MEASURES: Pure-tone audiometry was performed preoperatively and
      postoperatively (3-6 wk) and the most recent long-term results (>= 12 mo).
      RESULTS: Ninety-nine ears in 90 patients had audiologic follow-up data over 12
      months. Sixty-seven ears (68%) underwent SFS, 16 (16%) STAMP, and 16 (16%) CSM.
      There was significant improvement in average air conduction (AC) thresholds and
      air-bone gap (ABG) for all techniques. Mean ABG for SFS closed from 29 to 7.1 dB
      (SD, 6.0), for STAMP from 29 to 3.8 dB (SD, 5.8 dB), and for CSM from 34 to 20 dB
      (SD, 8.2 dB). AC results were better in the STAMP than in the SFS group,
      especially in high frequencies. Bone conduction improvements were seen in all
      groups, highest in STAMP (4.3 dB) and CSM (3.8 dB) groups, but the differences
      between groups were not statistically significant. CONCLUSION: Satisfactory
      hearing results were achieved with all the techniques, and STAMP showed better
      hearing outcomes, especially in high frequencies. CSM is a good option for
      children and patients in whom it is desirable to avoid a footplate fenestration
      or prosthesis. CSM and STAMP had significantly higher rates of revision for
      refixation than SFS.

PMID- 24569797
TI  - Bacterial invasion of the inner ear in association with pneumococcal meningitis.
AB  - OBJECTIVE: To examine the pathways of bacterial invasion and subsequent spreading
      in the inner ear during pneumococcal meningitis. STUDY DESIGN: A well-established
      adult rat model of Streptococcus pneumoniae meningitis was used. METHODS: Thirty
      rats were inoculated intrathecally with S. pneumoniae serotype 1, 3 or 9 V and
      received no additional treatment. The rats were sacrificed when reaching terminal
      illness or on Day 7 and then prepared for serial sectioning and PAS-Alcian blue
      staining for light microscopy. RESULTS: During the first few days after
      inoculation, bacteria invade the inner ear through the cochlear aqueduct, into
      the scala tympani of the cochlea (perilymphatic space). From here, bacteria
      spreads apically toward the helicotrema and subsequently basally through the
      scala vestibuli, toward the vestibule and the vestibular system. When the
      bacteria after 5 to 6 days had reached scala vestibuli of the basal turn of the
      cochlea, hematogenous spreading occurred to the spiral ligament and into the
      cochlear endolymph, subsequently to the vestibular endolymph. We found no
      evidence of alternative routes for bacterial invasion in the inner ear. Several
      internal barriers to bacterial spreading were found within the inner ear.
      Bacterial elimination was evidenced by engulfment by macrophages within the inner
      ear. CONCLUSION: From the meninges, pneumococci invade the inner ear through the
      cochlear aqueduct during the first days of infection, whereas hematogenous
      invasion via the spiral ligament capillary bed occur at later stages. Although
      internal barriers exist within the inner ear, the spreading of bacteria occurs
      via the natural pathways of the fluid compartments. Bacterial elimination occurs
      by local macrophage engulfment.

PMID- 24569796
TI  - Cochlear implantation in patients with chronic suppurative otitis media.
AB  - OBJECTIVE: To determine the safety, efficacy, and outcomes of cochlear
      implantation in patients with chronic suppurative otitis media (CSOM). STUDY
      DESIGN: Retrospective case review. SETTING: Tertiary referral center with large
      cochlear implant program. PATIENTS: Nineteen patients with CSOM who underwent
      cochlear implantation were identified. Case history, timing of surgical
      procedures, complications, infections, and postimplant audiometric scores
      (Hearing in Noise Test [HINT], City University of New York Sentences [CUNY], and
      Central Institute for the Deaf Sentences [CID]) were evaluated. MAIN OUTCOME
      MEASURES: Rates of postoperative infections and complications as well as
      postimplant auditory performance. RESULTS: Twelve patients underwent a staged
      procedure involving canal wall down mastoidectomy or radical revision
      mastoidectomy with middle ear and mastoid obliteration and closure of the
      external auditory canal followed by cochlear implantation approximately 5 months
      later. Seven patients were implanted in a single procedure. There were no
      infections or medical complications after implantation. On average, patients had
      excellent audiometric scores at 1 year postimplantation (mean sentence test, 79%;
      SD, 14), and these scores were comparable to our general population (mean
      sentence test, 71%; SD, 32). CONCLUSION: Cochlear implant patients with CSOM have
      no increased risk of postoperative infections or complications. These patients
      have excellent outcomes with audiometric scores comparable to the general
      cochlear implant population. Cochlear implantation is a safe and effective
      treatment for patients with profound hearing loss secondary to CSOM.

PMID- 24569798
TI  - Finding a place for grief in the workplace.

PMID- 24569799
TI  - Factors associated with the length of stay of patients discharged from emergency
      department in France.
AB  - OBJECTIVES: The length of stay in the emergency department (ED) has been proposed
      as an indicator of performance in many countries. We conducted a survey of length
      of stay in two large areas in France and tested the hypothesis that patient and
      ED-related variables may influence it. PATIENTS AND METHODS: During 2007, we
      examined lengths of stay in ambulatory patients, that is, excluding admitted
      patients. The following variables were considered: (a) at the patient level, age,
      sex, the day and month of the visit, and the French clinical classification of
      emergency patients (CCEP) class; (b) at the ED level, annual ED total number of
      visits, mean age, the proportions of patients less than 15 and more than 75
      years, and the proportions of admitted and clinically stable patients with CCEP
      class 1 and 2. A multilevel hierarchical analysis was carried out. RESULTS: We
      analyzed 988 591 visits in 53 EDs. The ED-specific median length of stay was 98
      (IQR: 62-137) min and the ED-specific median proportion of patients with length
      of stay of more than 4 h was 15 (5-24) %. There was a strong correlation between
      the ED-specific median length of stay and the ED-specific proportion of patients
      with a length of stay of more than 4 h (R=0.96, P<0.001). Using a multilevel
      analysis, only three variables were associated significantly with the length of
      stay: the age and the CCEP class of the patient, and the ED census. CONCLUSION:
      We observed that the length of stay in the ED needs to be stratified by case mix
      and the total number of visits of the ED.

PMID- 24569803
TI  - The amygdaloids.

PMID- 24569802
TI  - Tumor necrosis factor-related apoptosis-inducing ligand mediates the resolution
      of allergic airway inflammation induced by chronic allergen inhalation.
AB  - Allergic asthma can vanish over time either spontaneously or induced by allergen
      specific immunotherapy. In mice with established airway allergic inflammation,
      chronic intranasal (IN) allergen challenges decreases progressively airway
      allergic inflammation. Here we compared the contribution of different regulatory
      pathways that could be associated with this phenomenon, known as local
      inhalational tolerance. We found that inhalational tolerance was not associated
      with increased number of regulatory T cells or suppressive cytokines. Instead, it
      was associated with increased apoptosis of airway inflammatory leukocytes
      revealed by annexin-V staining and the expression of apical caspase 8 and
      effector caspase 3. Also, the transition from acute to chronic phase was
      associated with a shift in the expression of pro-allergic to pro-apoptotic
      molecules. The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)
      was found to be a key molecule in mediating resolution of allergic inflammation
      because anti-TRAIL treatment blocked apoptosis and increased the infiltration of
      T helper type 2 (Th2) cells and eosinophils. Notably, repeated IN treatment with
      recombinant TRAIL in established airway allergic inflammation augmented leukocyte
      apoptosis and decreased the frequency of interleukin-5-producing Th2 cells and
      eosinophils to airways. Our data indicate that TRAIL signaling is sufficient for
      downmodulation of allergic airway disease, suggesting a potential therapeutic use
      of TRAIL for asthma treatment. 

PMID- 24569801
TI  - The development and function of mucosal lymphoid tissues: a balancing act with
      micro-organisms.
AB  - Mucosal surfaces are constantly exposed to environmental antigens, colonized by
      commensal organisms and used by pathogens as points of entry. As a result, the
      immune system has devoted the bulk of its resources to mucosal sites to maintain
      symbiosis with commensal organisms, prevent pathogen entry, and avoid unnecessary
      inflammatory responses to innocuous antigens. These functions are facilitated by
      a variety of mucosal lymphoid organs that develop during embryogenesis in the
      absence of microbial stimulation as well as ectopic lymphoid tissues that develop
      in adults following microbial exposure or inflammation. Each of these lymphoid
      organs samples antigens from different mucosal sites and contributes to immune
      homeostasis, commensal containment, and immunity to pathogens. Here we discuss
      the mechanisms, mostly based on mouse studies, that control the development of
      mucosal lymphoid organs and how the various lymphoid tissues cooperate to
      maintain the integrity of the mucosal barrier. 

PMID- 24569805
TI  - Transcription could be the key to the selection advantage of mitochondrial
      deletion mutants in aging.
AB  - The mitochondrial theory of aging is widely popular but confronted by several
      apparent inconsistencies. On the one hand, mitochondrial energy production is of
      central importance to the health and proper functioning of cells, and single-cell
      studies have shown that mtDNA deletion mutants accumulate in a clonal fashion in
      various mammalian species, displacing the wild-type mtDNAs. On the other hand, no
      explanation exists yet for the clonal expansion of mtDNA mutants that is
      compatible with experimental observations. We present here a new idea based on
      the distinctive connection between transcription and replication of metazoan
      mtDNA. Bioinformatic analysis of mtDNA deletion spectra strongly supports the
      predictions of this hypothesis and identifies specific candidates for proteins
      involved in transcriptional control of mtDNA replication. Computer simulations
      show the mechanism to be compatible with the available data from short- and long
      lived mammalian species. 

PMID- 24569806
TI  - Secretory antibodies in breast milk promote long-term intestinal homeostasis by
      regulating the gut microbiota and host gene expression.
AB  - Maintenance of intestinal homeostasis requires a healthy relationship between the
      commensal gut microbiota and the host immune system. Breast milk supplies the
      first source of antigen-specific immune protection in the gastrointestinal tract
      of suckling mammals, in the form of secretory IgA (SIgA). SIgA is transported
      across glandular and mucosal epithelial cells into external secretions by the
      polymeric Ig receptor (pIgR). Here, a breeding scheme with polymeric Ig receptor
      sufficient and -deficient mice was used to study the effects of breast milk
      derived SIgA on development of the gut microbiota and host intestinal immunity.
      Early exposure to maternal SIgA prevented the translocation of aerobic bacteria
      from the neonatal gut into draining lymph nodes, including the opportunistic
      pathogen Ochrobactrum anthropi. By the age of weaning, mice that received
      maternal SIgA in breast milk had a significantly different gut microbiota from
      mice that did not receive SIgA, and these differences were magnified when the
      mice reached adulthood. Early exposure to SIgA in breast milk resulted in a
      pattern of intestinal epithelial cell gene expression in adult mice that differed
      from that of mice that were not exposed to passive SIgA, including genes
      associated with intestinal inflammatory diseases in humans. Maternal SIgA was
      also found to ameliorate colonic damage caused by the epithelial-disrupting agent
      dextran sulfate sodium. These findings reveal unique mechanisms through which
      SIgA in breast milk may promote lifelong intestinal homeostasis, and provide
      additional evidence for the benefits of breastfeeding. 

PMID- 24569809
TI  - Raman spectroscopy studies of dopant activation and free electron density of
      In(0.53)Ga(0.47)As via sulfur monolayer doping.
AB  - We present a Raman spectroscopy study of electron-phonon coupling in
      In0.53Ga0.47As epilayers doped via the sulfur-monolayer doping method. A high
      frequency coupled mode (HFCM) detected above 400 cm(-1) shifts with increasing
      charge carrier density and allows for extraction of the activated dopant
      concentrations. 

PMID- 24569807
TI  - Tyrosine sulfation in the second variable loop (V2) of HIV-1 gp120 stabilizes V2
      V3 interaction and modulates neutralization sensitivity.
AB  - Elicitation of broadly neutralizing antibodies is essential for the development
      of a protective vaccine against HIV-1. However, the native HIV-1 envelope adopts
      a protected conformation that conceals highly conserved sites of vulnerability
      from antibody recognition. Although high-definition structures of the monomeric
      core of the envelope glycoprotein subunit gp120 and, more recently, of a
      stabilized soluble gp140 trimer have been solved, fundamental aspects related to
      the conformation and function of the native envelope remain unresolved. Here, we
      show that the conserved central region of the second variable loop (V2) of gp120
      contains sulfated tyrosines (Tys173 and Tys177) that in the CD4-unbound prefusion
      state mediate intramolecular interaction between V2 and the conserved base of the
      third variable loop (V3), functionally mimicking sulfated tyrosines in CCR5 and
      anti-coreceptor-binding-site antibodies such as 412d. Recombinant gp120 expressed
      in continuous cell lines displays low constitutive levels of V2 tyrosine
      sulfation, which can be enhanced markedly by overexpression of the tyrosyl
      sulfotransferase TPST2. In contrast, virion-associated gp120 produced by primary
      CD4(+) T cells is inherently highly sulfated. Consistent with a functional role
      of the V2 sulfotyrosines, enhancement of tyrosine sulfation decreased binding and
      neutralization of HIV-1 BaL by monomeric soluble CD4, 412d, and anti-V3
      antibodies and increased recognition by the trimer-preferring antibodies PG9,
      PG16, CH01, and PGT145. Conversely, inhibition of tyrosine sulfation increased
      sensitivity to soluble CD4, 412d, and anti-V3 antibodies and diminished
      recognition by trimer-preferring antibodies. These results identify the
      sulfotyrosine-mediated V2-V3 interaction as a critical constraint that stabilizes
      the native HIV-1 envelope trimer and modulates its sensitivity to neutralization.

PMID- 24569808
TI  - TRPM2 channels mediate acetaminophen-induced liver damage.
AB  - Acetaminophen (paracetamol) is the most frequently used analgesic and antipyretic
      drug available over the counter. At the same time, acetaminophen overdose is the
      most common cause of acute liver failure and the leading cause of chronic liver
      damage requiring liver transplantation in developed countries. Acetaminophen
      overdose causes a multitude of interrelated biochemical reactions in hepatocytes
      including the formation of reactive oxygen species, deregulation of Ca(2+)
      homeostasis, covalent modification and oxidation of proteins, lipid peroxidation,
      and DNA fragmentation. Although an increase in intracellular Ca(2+) concentration
      in hepatocytes is a known consequence of acetaminophen overdose, its importance
      in acetaminophen-induced liver toxicity is not well understood, primarily due to
      lack of knowledge about the source of the Ca(2+) rise. Here we report that the
      channel responsible for Ca(2+) entry in hepatocytes in acetaminophen overdose is
      the Transient Receptor Potential Melanostatine 2 (TRPM2) cation channel. We show
      by whole-cell patch clamping that treatment of hepatocytes with acetaminophen
      results in activation of a cation current similar to that activated by H2O2 or
      the intracellular application of ADP ribose. siRNA-mediated knockdown of TRPM2 in
      hepatocytes inhibits activation of the current by either acetaminophen or H2O2.
      In TRPM2 knockout mice, acetaminophen-induced liver damage, assessed by the blood
      concentration of liver enzymes and liver histology, is significantly diminished
      compared with wild-type mice. The presented data strongly suggest that TRPM2
      channels are essential in the mechanism of acetaminophen-induced hepatocellular
      death. 

PMID- 24569811
TI  - A case for "reasonable discrimination".

PMID- 24569810
TI  - Personal exposure to inhalable dust and the specific latex aero-allergen, Hev
      b6.02, in latex glove manufacturing in Thailand.
AB  - OBJECTIVES: Latex product manufacturing is an important industry in south-east
      Asia but has the potential for considerable occupational exposure of workers to
      latex allergens. Although exposure to latex allergens can result in adverse
      health reactions, few studies to characterize this exposure have been conducted
      to date. This study therefore aimed to characterize current airborne inhalable
      dust and the specific allergen, Hev b 6.02, exposures in this industry in
      Thailand. METHODS: Workers were recruited from three factories in the southern
      part of Thailand. Full-shift inhalable dust personal air sampling was conducted
      using IOM sampling heads equipped with polytetrafluoroethylene filters at a 2.0 l
      min(-1) flowrate. After weighing to determine inhalable dust levels, filters were
      extracted and analysed for Hev b 6.02 using an enzyme immunometric assay.
      RESULTS: Two hundred and seventy-five workers agreed to participate, resulting in
      a total of 292 measurements. Geometric mean (GM) personal exposure to inhalable
      dust was 0.88 mg m(-3), but individual exposures up to 12.34 mg m(-3) were
      measured. The pattern of exposure was similar across factories, with highest
      exposures in the stripping (GM 2.08-4.05 mg m(-3) for the 3 factories) and
      tumbling departments (1.11-2.17 mg m(-3)). Within-worker (day-to-day) variability
      contributed 92% to total variability. The Hev b 6.02 exposure pattern was similar
      with time-weighted average GM exposure levels in the oldest factory ranging from
      8.7 mg m(-3) in the laboratory to 30.2mg m(-3) in the stripping department. In
      contrast to inhalable dust exposure, total exposure variability was primary
      driven by variability between workers (67%). CONCLUSIONS: Workers in these latex
      product factories get routinely exposed to measurable Hev b 6.02 levels, which
      may give rise to increased incidence of allergic symptoms and occupational
      asthma. Also, in this measurement campaign a 10mg m(-3), but not 15 mg m(-3),
      occupational exposure limit for inhalable dust was occasionally exceeded. Highest
      Hev b 6.02 exposures were found in the stripping and tumbling departments, which
      would be natural targets for interventions aimed at reducing exposure.

PMID- 24569812
TI  - The Effects of Topic Knowledge on Intelligibility and Lexical Segmentation in
      Hypokinetic and Ataxic Dysarthria.
AB  - Benefits to speech intelligibility can be achieved by enhancing a listener's
      ability to decipher it. However, much remains to be learned about the variables
      that influence the effectiveness of various listener-based manipulations. This
      study examined the benefit of providing listeners with the topic of some phases
      produced by speakers with either hypokinetic or ataxic dysarthria. Total and
      topic word accuracy, topic-related substitutions, and lexical boundary errors
      were calculated from the listener transcripts. Data were compared with those who
      underwent a familiarization process (reported by Liss, Spitzer, Caviness, &
      Adler, 2002) and with those inexperienced with disordered speech (reported by
      Liss Spitzer, Caviness, & Adler, 2000). Results revealed that listeners of ataxic
      speech provided with topic knowledge obtained higher intelligibility scores than
      naive listeners. The magnitude of benefit was similar to the familiarization
      condition. However, topic word and word substitution analyses revealed different
      underlying perceptual mechanisms responsible for the observed benefit. No
      differences attributable to listening condition were discovered in lexical
      segmentation patterns. Overall, the results support the need for further study of
      listener-based manipulations to elucidate the mechanisms responsible for the
      observed perceptual benefits for each dysarthria type.

PMID- 24569814
TI  - Plasma angiopoietin-1 is lower after ischemic stroke and associated with major
      disability but not stroke incidence.
AB  - BACKGROUND AND PURPOSE: Studies in rodent models suggest that upregulating
      angiopoietin-1 (Angpt1) improves stroke outcomes. The aims of this study were to
      assess the association of plasma Angpt1 with stroke occurrence and outcome.
      METHODS: Plasma Angpt1 was measured in 336 patients who had experienced a recent
      stroke and 321 healthy controls with no stroke history. Patients with stroke
      (n=285) were reassessed at 3 months and plasma Angpt1 concentration on admission
      compared between those with severe and minor disability as assessed by the
      modified Rankin scale. In a separate cohort of 4032 community-acquired older men
      prospectively followed for a minimum of 6 years, the association of plasma Angpt1
      with stroke incidence was examined. RESULTS: Median plasma Angpt1 was 3-fold
      lower in patients who had experienced a recent stroke (6.42, interquartile range,
      4.26-9.53 compared with 17.36; interquartile range, 14.01-22.46 ng/mL; P<0.001)
      and remained associated with stroke after adjustment for other risk factors.
      Plasma Angpt1 concentrations on admission were lower in patients who had severe
      disability or died at 3 months (median, 5.52; interquartile range, 3.81-8.75
      ng/mL for modified Rankin scale 3-6; n=91) compared with those with minor
      disability (median, 7.04; interquartile range, 4.75-9.92 ng/mL for modified
      Rankin scale 0-2; n=194), P=0.012, and remained negatively associated with severe
      disability or death after adjusting for other risk factors. Plasma Angpt1 was not
      predictive of stroke incidence in community-dwelling older men. CONCLUSIONS:
      Plasma Angpt1 concentrations are low after ischemic stroke particularly in
      patients with poor stroke outcomes at 3 months. Interventions effective at
      upregulating Angpt1 could potentially improve stroke outcomes.

PMID- 24569813
TI  - Small ubiquitin-like modifier 3-modified proteome regulated by brain ischemia in
      novel small ubiquitin-like modifier transgenic mice: putative protective
      proteins/pathways.
AB  - BACKGROUND AND PURPOSE: Small ubiquitin-like modifier (SUMO) conjugation is a
      post-translational modification associated with many human diseases.
      Characterization of the SUMO-modified proteome is pivotal to define the
      mechanistic link between SUMO conjugation and such diseases. This is particularly
      evident for SUMO2/3 conjugation, which is massively activated after brain
      ischemia/stroke, and is believed to be a protective response. The purpose of this
      study was to perform a comprehensive analysis of the SUMO3-modified proteome
      regulated by brain ischemia using a novel SUMO transgenic mouse. METHODS: To
      enable SUMO proteomics analysis in vivo, we generated transgenic mice
      conditionally expressing tagged SUMO1-3 paralogues. Transgenic mice were
      subjected to 10 minutes forebrain ischemia and 1 hour of reperfusion. SUMO3
      conjugated proteins were enriched by anti-FLAG affinity purification and analyzed
      by liquid chromatography-tandem mass spectrometry. RESULTS: Characterization of
      SUMO transgenic mice demonstrated that all 3 tagged SUMO paralogues were
      functionally active, and expression of exogenous SUMOs did not modify the
      endogenous SUMOylation machinery. Proteomics analysis identified 112 putative
      SUMO3 substrates of which 91 candidates were more abundant in the ischemia group
      than the sham group. Data analysis revealed processes/pathways with putative
      neuroprotective functions, including glucocorticoid receptor signaling, RNA
      processing, and SUMOylation-dependent ubiquitin conjugation. CONCLUSIONS: The
      identified proteins/pathways modulated by SUMOylation could be the key to
      understand the mechanisms linking SUMOylation to neuroprotection, and thus
      provide new promising targets for therapeutic interventions. The new transgenic
      mouse will be an invaluable platform for analyzing the SUMO-modified proteome in
      models of human disorders and thereby help to mechanistically link SUMOylation to
      the pathological processes.

PMID- 24569815
TI  - Increasing use of computed tomographic perfusion and computed tomographic
      angiograms in acute ischemic stroke from 2006 to 2010.
AB  - BACKGROUND AND PURPOSE: Our objective was to study nationwide utilization trends
      of computed tomographic (CT) angiogram (CTA) and CT perfusion (CTP) in acute
      ischemic stroke and particularly in the context of use of reperfusion therapies.
      METHODS: We reviewed the Premier Perspective Database for ischemic stroke-related
      hospitalizations of adult patients during a 5-year period, 2006 to 2010. Use of
      multimodal CT-based imaging and reperfusion therapies was determined through the
      procedure and billing codes. Logistic regression was used to identify predictors
      of utilization of imaging studies and reperfusion treatments. RESULTS: An
      increasing proportion of ischemic strokes received CTA each year: 3.8% in 2006,
      5.6% in 2007, 6.5% in 2008, 7.5% in 2009, and 9.1% in 2010 (P<0.0001). The
      proportion of acute strokes that were imaged with CTP imaging also increased each
      year: 0.05% in 2006, 0.05% in 2007, 0.9% in 2008, 2.2% in 2009, and 2.9% in 2010
      (P<0.0001). Reperfusion treatment was more common among those who were imaged
      with CTA (13.0%) and CTP (17.6%) compared with those with CT head alone (4.0%;
      P<0.0001). Specifically, higher rates of recombinant tissue-type plasminogen
      activator were observed in CTA (10.2%) and CTP (11.4%) compared with those with
      CT head alone (3.8%; P<0.0001). Similarly, higher rates of mechanical embolectomy
      were observed in CTA (2.8%) and CTP (6.3%) compared with those with CT head alone
      (0.2%; P<0.0001). CONCLUSIONS: There was a marked increase in the rate of CTA and
      CTP studies in setting of acute ischemic stroke from 2006 to 2010, and both
      modalities were associated with increased reperfusion therapy use.

PMID- 24569816
TI  - Effect of collateral blood flow on patients undergoing endovascular therapy for
      acute ischemic stroke.
AB  - BACKGROUND AND PURPOSE: Our aim was to determine the relationships between
      angiographic collaterals and diffusion/perfusion findings, subsequent infarct
      growth, and clinical outcome in patients undergoing endovascular therapy for
      ischemic stroke. METHODS: Sixty patients with a thrombolysis in cerebral
      infarction (TICI) score of 0 or 1 and internal carotid artery/M1 occlusion at
      baseline were evaluated. A blinded reader assigned a collateral score using a
      previous 5-point scale, from 0 (no collateral flow) to 4 (complete/rapid
      collaterals to the entire ischemic territory). The analysis was dichotomized to
      poor flow (0-2) versus good flow (3-4). Collateral score was correlated with
      baseline National Institutes of Health Stroke Scale, diffusion-weighted imaging
      volume, perfusion-weighted imaging volume (Tmax >=6 seconds), TICI reperfusion,
      infarct growth, and modified Rankin Scale score at day 90. RESULTS: Collateral
      score correlated with baseline National Institutes of Health Stroke Scale
      (P=0.002) and median volume of tissue at Tmax >=6 seconds (P=0.009). Twenty-nine
      percent of patients with poor collateral flow had TICI 2B-3 reperfusion versus
      65.5% with good flow (P=0.009). Patients with poor collaterals who reperfused
      (TICI 2B-3) were more likely to have a good functional outcome (modified Rankin
      Scale score 0-2 at 90 days) compared with patients who did not reperfuse (odds
      ratio, 12; 95% confidence interval, 1.6-98). There was no difference in the rate
      of good functional outcome after reperfusion in patients with poor collaterals
      versus good collaterals (P=1.0). Patients with poor reperfusion (TICI 0-2a)
      showed a trend toward greater infarct growth if they had poor collaterals versus
      good collaterals (P=0.06). CONCLUSIONS: Collaterals correlate with baseline
      National Institutes of Health Stroke Scale, perfusion-weighted imaging volume,
      and good reperfusion. However, target mismatch patients who reperfuse seem to
      have favorable outcomes at a similar rate, irrespective of the collateral score.
      CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique
      identifier: NCT01349946.

PMID- 24569817
TI  - Elevated levels of hemoglobin A1c are associated with cerebral white matter
      disease in patients with stroke.
AB  - BACKGROUND AND PURPOSE: This study was conducted to investigate the association
      of cerebral white matter disease (WMD) on MRI with vascular risk factors and
      laboratory findings in consecutive first acute ischemic stroke patients. METHODS:
      Acute ischemic stroke patients underwent MRI <=24 hours after stroke onset and
      follow-up on day 2. WMD was scored on fluid attenuated inversion recovery MRI
      according to the Wahlund score. Vascular risk factors and laboratory parameters
      were assessed during hospital stay. Univariate and multiple logistic regression
      analyses were performed. RESULTS: We included 512 patients with first acute
      ischemic stroke (mean age, 68.5 [SD, 13.2] years; 192 women (37.5%); median
      National Institutes of Health Stroke Scale on admission, 3 [interquartile range,
      1-6]; and median Wahlund score, 4 [interquartile range, 2-9]). WMD was present in
      460 (89.8%) patients. In univariate analysis, age, arterial hypertension, reduced
      estimated glomerular filtration rate, hemoglobin A1c (HbA1c) levels, diabetes
      mellitus, and female sex were associated with the presence of WMD (P<0.05). In
      multiple regression analysis, age, arterial hypertension, and elevated levels of
      HbA1c (P<0.05) remained independently associated with the extent of WMD.
      CONCLUSIONS: Among known risk factors, higher levels of HbA1c were associated
      with cerebral WMD in stroke patients. This may suggest that chronic disturbance
      of glycemia measured by HbA1c plays a role in the pathophysiology of WMD.
      CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique
      identifier: NCT00715533.

PMID- 24569818
TI  - Salivary gland scintigraphy in Sjogren's syndrome. Comparison of the diagnostic
      performance of visual and semiquantitative analysis.
AB  - The aim of this study was to compare the diagnostic utility of visual versus semi
      quantitative analysis of salivary gland scintigraphy in the diagnosis of
      Sjogren's syndrome (SS). PATIENTS, METHODS: 99mTc-pertechnetate salivary gland
      scintigraphy was performed in 145 patients (133 women, 12 men) with clinically
      suspicious SS. The images were interpreted with visual and semiquantitative
      methods and the diagnostic performances for SS were compared using uptake and
      excretory functional parameters. RESULTS: In total, 76 patients (52.4%) were
      finally diagnosed with SS. The sensitivity, specificity, positive predictive
      value, negative predictive value, and accuracy of visual analysis for the
      diagnosis of SS were 88.2%, 48.6%, 65.1%, 79.1%, and 69.2%, respectively.
      Semiquantitative values, the area under the ROC curve for uptake ratio and
      percentage excretion in the right salivary glands were significantly greater than
      0.5 (p < 0.05). However, the percentage excretion in the left salivary glands did
      not show a statistically significant diagnostic ability for SS. The diagnostic
      ability of visual assessment was greater than that of the semiquantitative method
      in terms of evaluating uptake and excretory function in the submandibular glands.
      CONCLUSION: Visual analysis of salivary gland scintigraphy showed greater
      diagnostic utility than semiquantitative assessment in the diagnosis of SS,
      especially in the submandibular glands.

PMID- 24569819
TI  - Real-world outcomes in patients with chronic hepatitis C: primary results of the
      PROBE study.
AB  - BACKGROUND: This large prospective multicentre cohort study aimed to improve
      knowledge of therapy for chronic hepatitis C (CHC) in real clinical practice.
      METHODS: A diverse population of adults with CHC including patients with comorbid
      conditions, laboratory abnormalities and demographic features [comorbidities or
      special populations (CSP)] who were under-represented or excluded from
      peginterferon registration studies was treated with peginterferon alpha-2a (40
      kDa) or alpha-2b (12 kDa) plus ribavirin at the investigator's discretion.
      RESULTS: During the study, 5399 treatment-naive patients [2527 (46.8%) with CSP]
      received peginterferon alpha-2a (n=3513, 65.1%) or peginterferon alpha-2b
      (n=1886, 34.9%). The sustained virological response rate was 56.6% (3057/5399)
      overall, 59.7% (1716/2872) in patients without CSP and 53.1% (1341/2527) in
      patients with CSP. Significant predictors of sustained virological response
      included hepatitis C virus genotype 2 or 3 infection, absence of cirrhosis,
      hepatitis C virus RNA<=500 000 IU/ml, alanine transaminase quotient >3* the upper
      limit of normal, age <=65 years, BMI<25 kg/m, at least 80% of the planned
      exposure to peginterferon and ribavirin and prescription of peginterferon alpha
      2a. CONCLUSION: The results provide detailed information on the outcome of
      therapy for CHC in a diverse Italian population that included a large number of
      patients with CSP and provides an insight into the generalizability of the
      results obtained in the more restricted setting of randomized registration
      trials.

PMID- 24569820
TI  - Comparison of telbivudine efficacy in treatment-naive patients with hepatitis B
      virus-related compensated and decompensated cirrhosis in 96 weeks.
AB  - OBJECTIVE: Data are limited for comparison of the long-term efficacy of
      telbivudine (LdT) between hepatitis B virus (HBV)-related compensated and
      decompensated cirrhosis. The aim of this study was to compare the efficacy of LdT
      in treatment-naive patients with HBV-related compensated and decompensated
      cirrhosis in 96 weeks. PATIENTS AND METHODS: We reviewed the data of 65
      compensated and 62 decompensated cirrhotic patients treated with LdT for 96
      weeks, and compared the difference in the related indicators before and after
      treatment between the groups. RESULTS: Alanine aminotransferase normalized rate
      was significantly higher in the compensated group than in the decompensated group
      at weeks 12 and 24 (67.7 vs. 40.3% and 78.5 vs. 53.2%, respectively, P<0.01).
      Albumin level was much higher than the baseline at week 24 in the compensated
      group (35.1+/-6.2 vs. 39.9+/-5.1, P<0.01), but significance was observed from
      week 48 onwards in the decompensated group (29.8+/-3.7 vs. 33.7+/-3.8, P<0.05).
      The Child-Turcotte-Puge score either improved or remained steady in both groups.
      The HBV DNA negativity rate at week 12 (56.9 vs. 32.3%, P<0.01) was higher,
      whereas the drug resistance rate was lower (P>0.05), in the compensated group
      than in the decompensated group. The degree of esophageal varix was alleviated,
      including 11 (16.9%) compensated and four (6.5%) decompensated cirrhotic
      patients. Liver stiffness was significantly decreased in the compensated group
      compared with the baseline [19.1 (7.3-32.6) vs. 14.8 (7.4-32.5), P<0.01];
      however, there was no statistical significance in the decompensated group
      compared with the baseline [30.5 (9.1-55.0) vs. 29.9 (8.4-53.2), P>0.05].
      CONCLUSION: Long-term LdT treatment showed superior virological, biochemical, and
      clinical efficacy in the compensated cirrhotic patients. Therefore, we emphasized
      the importance of early antiviral treatment, which may improve the prognosis of
      cirrhotic patients.

PMID- 24569821
TI  - Prevalence of gastric precancerous conditions: a systematic review and meta
      analysis.
AB  - Several reports of estimates for precancerous conditions for gastric
      adenocarcinoma can be found in the current literature. Our aim was to
      systematically review and estimate the prevalence of gastric precancerous
      conditions. Four databases (PubMed, Scopus, Web of Knowledge and EBSCO Academic
      Search Complete) were searched for original manuscripts addressing the presence
      of chronic atrophic gastritis (CAG) or intestinal metaplasia (IM). Subgroup
      analysis was carried out on methods of diagnosis, type of population, incidence
      of gastric cancer, sex, Helicobacter pylori status, age and extent of conditions.
      Overall, 107 studies were included. The worldwide prevalence of CAG in the
      general population was 33% (95% confidence interval: 26-41%) when considering
      biopsies (n=20 912) and 24% (19-29%) if serology (n=51 886) was used, whereas IM
      was found in 25% (19-30%) (n=30 960). Estimates for CAG were higher in countries
      with a high incidence of gastric cancer (42 vs. 23%), men (32 vs. 28%), H. pylori
      positive (46 vs. 17%) and if aged 40 years or older (48 vs. 22%). The prevalence
      of extensive conditions was 16% (12-20%) for CAG and 13% (9.0-17%) for IM. When
      comparing countries with high versus low to moderate incidence of gastric cancer,
      significant differences were achieved for CAG: 27% (12-36%) versus 7.3% (5.6
      9.0%). Worldwide, one-third and one-fourth of individuals may harbour CAG and IM,
      respectively. In countries with a high incidence of gastric cancer, the
      prevalence of extensive conditions may increase up to 27% and these patients
      represent a high-risk population to whom endoscopic surveillance should be
      offered according to recent guidelines. 

PMID- 24569823
TI  - Electronic hybridization detection in microarray format and DNA genotyping.
AB  - We describe an approach to substituting a fluorescence microarray with a surface
      made of an arrangement of electrolyte-gated field effect transistors. This was
      achieved using a dedicated blocking of non-specific interactions and comparing
      threshold voltage shifts of transistors exhibiting probe molecules of different
      base sequence. We apply the approach to detection of the 35delG mutation, which
      is related to non-syndromic deafness and is one of the most frequent mutations in
      humans. The process involves barcode sequences that are generated by Tas-PCR, a
      newly developed replication reaction using polymerase blocking. The barcodes are
      recognized by hybridization to surface attached probes and are directly detected
      by the semiconductor device. 

PMID- 24569825
TI  - What's there, distinctly, when and where?

PMID- 24569826
TI  - PIWIL1 protein power targets tau therapy.

PMID- 24569827
TI  - Inhaling: endocannabinoids and food intake.

PMID- 24569828
TI  - Crouching tiger, hidden dimensions.

PMID- 24569829
TI  - Oxytocin for all senses.

PMID- 24569830
TI  - Neurobiology of premature brain injury.
AB  - Every year in the United States, an estimated 500,000 babies are born preterm
      (before 37 completed weeks of gestation), and this number is rising, along with
      the recognition of brain injuries due to preterm delivery. A common underlying
      pathogenesis appears to be perinatal hypoxia induced by immature lung
      development, which causes injury to vulnerable neurons and glia. Abnormal growth
      and maturation of susceptible cell types, particularly neurons and
      oligodendrocytes, in preterm babies with very low birth weight is associated with
      decreased cerebral and cerebellar volumes and increases in cerebral ventricular
      size. Here we reconcile these observations with recent studies using models of
      perinatal hypoxia that show perturbations in the maturation and function of
      interneurons, oligodendrocytes and astroglia. Together, these findings suggest
      that the global mechanism by which perinatal hypoxia alters development is
      through a delay in maturation of affected cell types, including astroglia,
      oligodendroglia and neurons. 

PMID- 24569832
TI  - Bacterial-mediated knockdown of tumor resistance to an oncolytic virus enhances
      therapy.
AB  - Oncolytic viruses (OVs) and bacteria share the property of tumor-selective
      replication following systemic administration. In the case of nonpathogenic
      bacteria, tumor selectivity relates to their ability to grow extracellularly
      within tumor stroma and is therefore ideally suited to restricting the production
      of bacterially produced therapeutic agents to tumors. We have previously shown
      the ability of the type 1 interferon antagonist B18R to enhance the replication
      and spread of vesicular stomatitis virus (VSV) by overcoming related cellular
      innate immunity. In this study, we utilized nonpathogenic bacteria (E. coli)
      expressing B18R to facilitate tumor-specific production of B18R, resulting in a
      microenvironment depleted of bioactive antiviral cytokine, thus "preconditioning"
      the tumor to enhance subsequent tumor destruction by the OV. Both in vitro and in
      vivo infection by VSVDelta51 was greatly enhanced by B18R produced from E. coli.
      Moreover, a significant increase in therapeutic efficacy resulted from
      intravenous (i.v.) injection of bacteria to tumor-bearing mice 5 days prior to
      i.v. VSVDelta51 administration, as evidenced by a significant reduction in tumor
      growth and increased survival in mice. Our strategy is the first example where
      two such diverse microorganisms are rationally combined and demonstrates the
      feasibility of combining complementary microorganisms to improve therapeutic
      outcome.

PMID- 24569831
TI  - Changing concepts of working memory.
AB  - Working memory is widely considered to be limited in capacity, holding a fixed,
      small number of items, such as Miller's 'magical number' seven or Cowan's four.
      It has recently been proposed that working memory might better be conceptualized
      as a limited resource that is distributed flexibly among all items to be
      maintained in memory. According to this view, the quality rather than the
      quantity of working memory representations determines performance. Here we
      consider behavioral and emerging neural evidence for this proposal. 

PMID- 24569834
TI  - miR-29b as a therapeutic agent for angiotensin II-induced cardiac fibrosis by
      targeting TGF-beta/Smad3 signaling.
AB  - Loss of miR-29 is associated with cardiac fibrosis. This study examined the role
      and therapeutic potential of miR-29 in mouse model of hypertension induced by
      angiotensin II (AngII). By using microRNA microarray, in situ hybridization, and
      real-time polymerase chain reaction, we found that AngII-induced cardiac fibrosis
      in the hypertensive heart and in cultured cardiac fibroblasts were associated
      with downregulation of miR-29a-c via a Smad3-dependent mechanism. In vitro
      knockdown of miR-29b enhanced but overexpression of miR-29b inhibited AngII
      induced fibrosis, revealing a protective role of miR-29b in cardiac fibrosis in
      response to AngII. This was further demonstrated in vivo by the ability of
      overexpressing miR-29b in the mouse heart to prevent AngII-mediated cardiac
      fibrosis and cardiac dysfunction. Importantly, we also found that restored miR
      29b in the established hypertensive heart was capable of blocking progressive
      cardiac fibrosis and improving cardiac dysfunction, demonstrating a therapeutic
      potential of miR-29b for chronic heart disease. Further studies revealed that
      targeting the transforming growth factor (TGF)-beta1 coding sequence region,
      thereby inhibiting TGF-beta/Smad3 signaling, could be a new mechanism by which
      miR-29b inhibited AngII-induced cardiac fibrosis. In conclusion, miR-29b plays a
      protective role in AngII-mediated cardiac remodeling and may be a therapeutic
      agent for cardiac fibrosis by targeting the TGF-beta/Smad3 pathway. 

PMID- 24569833
TI  - Human skeletal muscle-derived CD133(+) cells form functional satellite cells
      after intramuscular transplantation in immunodeficient host mice.
AB  - Stem cell therapy is a promising strategy for treatment of muscular dystrophies.
      In addition to muscle fiber formation, reconstitution of functional stem cell
      pool by donor cells is vital for long-term treatment. We show here that some
      CD133(+) cells within human muscle are located underneath the basal lamina of
      muscle fibers, in the position of the muscle satellite cell. Cultured hCD133(+)
      cells are heterogeneous and multipotent, capable of forming myotubes and reserve
      satellite cells in vitro. They contribute to extensive muscle regeneration and
      satellite cell formation following intramuscular transplantation into irradiated
      and cryodamaged tibialis anterior muscles of immunodeficient Rag2-/gamma chain
      /C5-mice. Some donor-derived satellite cells expressed the myogenic regulatory
      factor MyoD, indicating that they were activated. In addition, when transplanted
      host muscles were reinjured, there was significantly more newly-regenerated
      muscle fibers of donor origin in treated than in control, nonreinjured muscles,
      indicating that hCD133(+) cells had given rise to functional muscle stem cells,
      which were able to activate in response to injury and contribute to a further
      round of muscle regeneration. Our findings provide new evidence for the location
      and characterization of hCD133(+) cells, and highlight that these cells are
      highly suitable for future clinical application. 

PMID- 24569838
TI  - Magnetic edge-states in nanographene, HNO3-doped nanographene and its residue
      compounds of nanographene-based nanoporous carbon.
AB  - We investigated the magnetic and electronic properties of nanographene and its
      charge transfer effect, using near edge X-ray absorption fine structure (NEXAFS),
      magnetic susceptibility and ESR measurements, and elemental analysis, with the
      employment of nanoporous carbon, which consists of a three dimensional disordered
      network of loosely stacked nanographene sheets, in relation to the host-guest
      interaction with HNO3 as the electron-accepting guest. The adsorption of electron
      acceptor HNO3 decreases the intensity of the edge state peak in NEXAFS as a
      result of the charge-transfer-induced Fermi energy downshift, in agreement with
      the decrease in the edge-state spin concentration, and it also induces the
      structural expansion, which makes the inter-nanographene sheet distance
      elongated, resulting in weakening of the inter-nanographene-sheet
      antiferromagnetic interaction as evidenced by the decrease in the Weiss
      temperature. In addition, the decomposition of HNO3, which takes place with the
      electron-rich edge state as an oxidation catalyst, results in the creation of
      oxygen/nitrogen-containing functional groups bonded to the periphery of the
      nanographene sheets. Heat-treatment of the HNO3-ACFs under evacuation desorbs the
      HNO3 molecules completely, though a part of the oxygen/nitrogen-containing
      species remains strongly bonded to the edge even at a high temperature of ~800 
      degrees C, according to NEXAFS and elemental analysis results. These remaining
      species participate in the charge transfer, modifying the electronic structure as
      observed with the decrease in the orbital susceptibility and the strengthening of
      the inter-nanographene-sheet antiferromagnetic interaction. 

PMID- 24569837
TI  - Living well with HIV in Nigeria? Stigma and survival challenges preventing
      optimum benefit from an ART clinic.
AB  - Thirty years into the HIV pandemic, the interactions of stigma, social and
      economic survival, and clinical interventions continue to be key to understanding
      and managing HIV at both personal and societal levels. With antiretroviral
      therapy, HIV is increasingly a chronic condition requiring lifelong treatment,
      near-perfect adherence, and support from both social networks and formal
      services. This study asked: is stigma still a significant problem for people
      living with HIV (PLHIV) who have secured access to antiretrovirals (ARVs)? How do
      PLHIV accessing ARVs in Nigeria experience the social, economic and health
      service supports intended to address their needs? What are the concerns and
      challenges of PLHIV and health workers regarding these supports? What are the
      implications for approaches to stigma and discrimination? This qualitative study
      at the Antiretroviral (ART) Clinic of the Osogbo State Hospital, Osun State,
      Nigeria involved in-depth interviews with 15 PLHIV who have been attending the
      clinic for at least one year, and three health workers. The results reveal both
      the diversity among even a small number of patients, and persistent cross-cutting
      themes of stigma, discrimination, poverty, and the psychological impacts of
      insecure livelihoods and well-intentioned but ultimately stigmatizing supports
      such as selective food parcels. Both population-based interventions against
      stigma and poverty, as well as micro-level, contextualized attention to
      patients', families' and health workers' fear of social exclusion and infection
      at a clinic and community level are needed if patients - and society - are to
      live well with HIV in Nigeria. 

PMID- 24569835
TI  - Colocalized delivery of rapamycin and paclitaxel to tumors enhances synergistic
      targeting of the PI3K/Akt/mTOR pathway.
AB  - Ongoing clinical trials target the aberrant PI3K/Akt/mammalian target of
      rapamycin (mTOR) pathway in breast cancer through administration of rapamycin, an
      allosteric mTOR inhibitor, in combination with paclitaxel. However, synergy may
      not be fully exploited clinically because of distinct pharmacokinetic parameters
      of drugs. This study explores the synergistic potential of site-specific,
      colocalized delivery of rapamycin and paclitaxel through nanoparticle
      incorporation. Nanoparticle drug loading was accurately controlled, and
      synergistic drug ratios established in vitro. Precise drug ratios were maintained
      in tumors 48 hours after nanoparticle administration to mice, at levels twofold
      greater than liver and spleen, yielding superior antitumor activity compared to
      controls. Simultaneous and preferential in vivo delivery of rapamycin and
      paclitaxel to tumors yielded mechanistic insights into synergy involving
      suppression of feedback loop Akt phosphorylation and its downstream targets.
      Findings demonstrate that a same time, same place, and specific amount approach
      to combination chemotherapy by means of nanoparticle delivery has the potential
      to successfully translate in vitro synergistic findings in vivo. Predictive in
      vitro models can be used to determine optimum drug ratios for antitumor efficacy,
      while nanoparticle delivery of combination chemotherapies in preclinical animal
      models may lead to enhanced understanding of mechanisms of synergy, ultimately
      opening several avenues for personalized therapy. 

PMID- 24569836
TI  - SNS01-T modulation of eIF5A inhibits B-cell cancer progression and synergizes
      with bortezomib and lenalidomide.
AB  - The high rates of recurrence and low median survival in many B-cell cancers
      highlight a need for new targeted therapeutic modalities. In dividing cells,
      eukaryotic translation initiation factor 5A (eIF5A) is hypusinated and involved
      in regulation of protein synthesis and proliferation, whereas the non-hypusinated
      form of eIF5A is a potent inducer of cell death in malignant cells. Here, we
      demonstrate the potential of modulating eIF5A expression as a novel approach to
      treating B-cell cancers. SNS01-T is a nonviral polyethylenimine-based
      nanoparticle, designed to induce apoptosis selectively in B-cell cancers by small
      interfering RNA-mediated suppression of hypusinated eIF5A and plasmid-based
      overexpression of a non-hypusinable eIF5A mutant. In this study, we show that
      SNS01-T is preferentially taken up by malignant B cells, inhibits tumor growth in
      multiple animal models of B-cell cancers without damaging normal tissues, and
      synergizes with the current therapies bortezomib and lenalidomide to inhibit
      tumor progression. The results collectively demonstrate the potential of SNS01-T
      as a novel therapeutic for treatment of a diverse range of B-cell malignancies. 

PMID- 24569839
TI  - Insulating to metallic transition of an oxidized boron nitride nanosheet coating
      by tuning surface oxygen adsorption.
AB  - Surface modification and functionalization are of fundamental importance in
      actual application of insulating coating, such as hexagon boron nitride (h-BN)
      nanosheet. Our first-principles calculations reveal that an oxidized h-BN
      monolayer supported by a Cu substrate exhibits metallic properties when O adatom
      vertically bonds with the B atom. This is mainly due to the hybridization of the
      p orbital of the BN layer and O adatom around the Fermi level. Charge transfer
      from the Cu substrate to the O atom stabilizes the formation of the vertical O-B
      bond. Injecting negative charges could trigger the migration of the O adatom from
      the B-N bond to B atom for metal or insulator-supported h-BN monolayer, which
      will lead to a metallic transition in the oxidized h-BN nanosheet. Our results
      provide a viable way to tune the electronic properties of surface h-BN coating
      through charge injection mediated O adsorption. 

PMID- 24569840
TI  - Iron Oxide-labeled Collagen Scaffolds for Non-invasive MR Imaging in Tissue
      Engineering.
AB  - Non-invasive imaging holds significant potential for implementation in tissue
      engineering. It can e.g. be used to monitor the localization and function of
      tissue-engineered implants, as well as their resorption and remodelling. Thus
      far, however, the vast majority of efforts in this area of research have focused
      on the use of ultrasmall super-paramagnetic iron oxide (USPIO) nanoparticle
      labeled cells, colonizing the scaffolds, to indirectly image the implant
      material. Reasoning that directly labeling scaffold materials might be more
      beneficial (enabling imaging also in case of non-cellularized implants), more
      informative (enabling the non-invasive visualization and quantification of
      scaffold degradation) and more easy to translate into the clinic (since cell-free
      materials are less complex from a regulatory point-of-view), we here prepared
      three different types of USPIO nanoparticles, and incorporated them both
      passively and actively (via chemical conjugation; during collagen crosslinking)
      into collagen-based scaffold materials. We furthermore optimized the amount of
      USPIO incorporated into the scaffolds, correlated the amount of entrapped USPIO
      with MR signal intensity, showed that the labeled scaffolds are highly
      biocompatible, demonstrated that scaffold degradation can be visualized using MRI
      and provided initial proof-of-principle for the in vivo visualization of the
      scaffolds. Consequently, USPIO-labeled scaffold materials seem to be highly
      suitable for image-guided tissue engineering applications.

PMID- 24569841
TI  - Is the decision on the use of biosimilar growth hormone based on high quality
      scientific evidence? - a systematic review.
AB  - BACKGROUND: The authors carried out a systematic and critical review of the
      scientific literature regarding the possible development of neutralising
      antibodies developed in patients treated with growth hormone biosimilars (defined
      as a drug expected to be similar to the originator or original pharmaceutical 
      European Medicines Agency) as compared to the reference drug. As a consequence,
      we discovered two major issues, namely, the poor quality of the comparative
      clinical trials and the poor quality of the antibody assays used during the
      trials. METHODS: The literature review was performed according to the principle
      of the Cochrane Collaboration and SBU. The electronic literature search included
      the databases PubMed, EMBASE and The Cochrane Library up to December 2012. Two
      independent reviewers assessed abstracts and full-text articles. RESULTS: The
      search identified 1,553 abstracts related to the subject. Only six articles
      contained data on biosimilar growth hormone or antibody results obtained with
      appropriate methods. None of the studies fulfilled the criteria for high quality
      randomised controlled trials. Qualitative rather than quantitative assays were
      used for monitoring antibody formation. CONCLUSIONS: It is our firm opinion ,
      that since biosimilars are not identical, emphasis must be placed on the quality
      of the comparative clinical trials performed and the quality of the analytical
      studies in order to guarantee patient safety. Clinical trials should follow
      established quality rules for controlled comparative randomised clinical trials.
      A whole set of new guidelines is required.

PMID- 24569843
TI  - CELLULOSE SYNTHASE-LIKE A2, a glucomannan synthase, is involved in maintaining
      adherent mucilage structure in Arabidopsis seed.
AB  - Mannans are hemicellulosic polysaccharides that are considered to have both
      structural and storage functions in the plant cell wall. However, it is not yet
      known how mannans function in Arabidopsis (Arabidopsis thaliana) seed mucilage.
      In this study, CELLULOSE SYNTHASE-LIKE A2 (CSLA2; At5g22740) expression was
      observed in several seed tissues, including the epidermal cells of developing
      seed coats. Disruption of CSLA2 resulted in thinner adherent mucilage halos,
      although the total amount of the adherent mucilage did not change compared with
      the wild type. This suggested that the adherent mucilage in the mutant was more
      compact compared with that of the wild type. In accordance with the role of CSLA2
      in glucomannan synthesis, csla2-1 mucilage contained 30% less mannosyl and
      glucosyl content than did the wild type. No appreciable changes in the
      composition, structure, or macromolecular properties were observed for nonmannan
      polysaccharides in mutant mucilage. Biochemical analysis revealed that cellulose
      crystallinity was substantially reduced in csla2-1 mucilage; this was supported
      by the removal of most mucilage cellulose through treatment of csla2-1 seeds with
      endo-beta-glucanase. Mutation in CSLA2 also resulted in altered spatial
      distribution of cellulose and an absence of birefringent cellulose microfibrils
      within the adherent mucilage. As with the observed changes in crystalline
      cellulose, the spatial distribution of pectin was also modified in csla2-1
      mucilage. Taken together, our results demonstrate that glucomannans synthesized
      by CSLA2 are involved in modulating the structure of adherent mucilage,
      potentially through altering cellulose organization and crystallization. 

PMID- 24569844
TI  - Arabidopsis VQ MOTIF-CONTAINING PROTEIN29 represses seedling deetiolation by
      interacting with PHYTOCHROME-INTERACTING FACTOR1.
AB  - Seedling deetiolation, a critical process in early plant development, is
      regulated by an intricate transcriptional network. Here, we identified VQ MOTIF
      CONTAINING PROTEIN29 (VQ29) as a novel regulator of the photomorphogenic response
      in Arabidopsis (Arabidopsis thaliana). We showed that 29 of the 34 VQ proteins
      present in Arabidopsis exhibit transcriptional activity in plant cells and that
      mutations in the VQ motif affect the transcriptional activity of VQ29. We then
      functionally characterized VQ29 and showed that the hypocotyl growth of plants
      overexpressing VQ29 is hyposensitive to far-red and low-intensity white light,
      whereas a vq29 loss-of-function mutant exhibits decreased hypocotyl elongation
      under a low intensity of far-red or white light. Consistent with this, VQ29
      expression is repressed by light in a phytochrome-dependent manner. Intriguingly,
      our yeast (Saccharomyces cerevisiae) two-hybrid, bimolecular fluorescence
      complementation, and coimmunoprecipitation assays showed that VQ29 physically
      interacts with PHYTOCHROME-INTERACTING FACTOR1 (PIF1). We then showed that VQ29
      and PIF1 directly bind to the promoter of a cell elongation-related gene,
      XYLOGLUCAN ENDOTRANSGLYCOSYLASE7, and coactivate its expression. Furthermore, the
      vq29 pif1 double mutant has shorter hypocotyls than either of the corresponding
      single mutants. Therefore, our study reveals that VQ29 is a negative
      transcriptional regulator of light-mediated inhibition of hypocotyl elongation
      that likely promotes the transcriptional activity of PIF1 during early seedling
      development. 

PMID- 24569845
TI  - Functional analysis of 3-hydroxy-3-methylglutaryl coenzyme a reductase encoding
      genes in triterpene saponin-producing ginseng.
AB  - Ginsenosides are glycosylated triterpenes that are considered to be important
      pharmaceutically active components of the ginseng (Panax ginseng 'Meyer') plant,
      which is known as an adaptogenic herb. However, the regulatory mechanism
      underlying the biosynthesis of triterpene saponin through the mevalonate pathway
      in ginseng remains unclear. In this study, we characterized the role of 3-hydroxy
      3-methylglutaryl coenzyme A reductase (HMGR) concerning ginsenoside biosynthesis.
      Through analysis of full-length complementary DNA, two forms of ginseng HMGR
      (PgHMGR1 and PgHMGR2) were identified as showing high sequence identity. The
      steady-state mRNA expression patterns of PgHMGR1 and PgHMGR2 are relatively low
      in seed, leaf, stem, and flower, but stronger in the petiole of seedling and
      root. The transcripts of PgHMGR1 were relatively constant in 3- and 6-year-old
      ginseng roots. However, PgHMGR2 was increased five times in the 6-year-old
      ginseng roots compared with the 3-year-old ginseng roots, which indicates that
      HMGRs have constant and specific roles in the accumulation of ginsenosides in
      roots. Competitive inhibition of HMGR by mevinolin caused a significant reduction
      of total ginsenoside in ginseng adventitious roots. Moreover, continuous dark
      exposure for 2 to 3 d increased the total ginsenosides content in 3-year-old
      ginseng after the dark-induced activity of PgHMGR1. These results suggest that
      PgHMGR1 is associated with the dark-dependent promotion of ginsenoside
      biosynthesis. We also observed that the PgHMGR1 can complement Arabidopsis
      (Arabidopsis thaliana) hmgr1-1 and that the overexpression of PgHMGR1 enhanced
      the production of sterols and triterpenes in Arabidopsis and ginseng. Overall,
      this finding suggests that ginseng HMGRs play a regulatory role in triterpene
      ginsenoside biosynthesis. 

PMID- 24569846
TI  - Genetic and physiological controls of growth under water deficit.
AB  - The sensitivity of expansive growth to water deficit has a large genetic
      variability, which is higher than that of photosynthesis. It is observed in
      several species, with some genotypes stopping growth in a relatively wet soil,
      whereas others continue growing until the lower limit of soil-available water.
      The responses of growth to soil water deficit and evaporative demand share an
      appreciable part of their genetic control through the colocation of quantitative
      trait loci as do the responses of the growth of different organs to water
      deficit. This result may be caused by common mechanisms of action discussed in
      this paper (particularly, plant hydraulic properties). We propose that expansive
      growth, putatively linked to hydraulic processes, determines the sink strength
      under water deficit, whereas photosynthesis determines source strength. These
      findings have large consequences for plant modeling under water deficit and for
      the design of breeding programs. 

PMID- 24569849
TI  - Surgical induction of metacarpal synostosis for treatment of ectrodactyly in a
      dog.
AB  - Ectrodactyly is a rare developmental anomaly of the distal part of the forelimb.
      It is characterized by the presence of an abnormal longitudinal soft tissue and
      osseous separation or cleft between the digits and the metacarpal bones. It can
      be associated with hypoplasia, aplasia and malformation of one or more bones of
      the antebrachium, carpus, metacarpus and digits. Unilateral ectrodactyly and
      moderate lameness were diagnosed in a young female dog. The dog was treated
      surgically with reconstruction of soft tissues and stabilization of the
      metacarpal bones by two nylon cerclage sutures. After three years a mild residual
      lameness was present. Radiographic signs of synostosis between the metacarpal
      bones II, III and IV with presence of a cleft between carpal bones II and III
      were observed.

PMID- 24569848
TI  - Incidental pancreatic cysts: natural history and diagnostic accuracy of a limited
      serial pancreatic cyst MRI protocol.
AB  - OBJECTIVES: To examine the natural history of incidentally detected pancreatic
      cysts and whether a simplified MRI protocol without gadolinium is adequate for
      lesion follow-up. METHODS: Over a 10-year period, 301-patients with asymptomatic
      pancreatic cysts underwent follow-up (45 months +/- 30). The magnetic resonance
      imaging (MRI) protocol included axial, coronal T2-weighted images, MR
      cholangiopancreatographic and fat suppressed T1-weighted sequences before and
      after gadolinium. Three radiologists independently reviewed the initial MRI, the
      follow-up studies using first only unenhanced images, then secondly gadolinium
      enhanced-sequences. Lesion changes during follow-up were recorded and the added
      value of gadolinium-enhanced sequences was determined by classifying the lesions
      into risk categories. RESULTS: Three hundred and one patients (1,174 cysts)
      constituted the study population. Only 35/301 patients (12 %) showed significant
      lesion change on follow-up. Using multivariate analysis the only independent
      factor of lesion growth (OR = 2.4; 95 % CI, 1.7-3.3; P < 0.001) and mural nodule
      development (OR = 1.9; 95 % CI, 1.1-3.4, P = 0.03) during follow-up was initial
      lesion size. No patient with a lesion initial size less than 2 cm developed
      cancer during follow-up. Intra-observer agreement with and without gadolinium
      enhancement ranged from 0.86 to 0.97. After consensus review of discordant cases,
      gadolinium-enhanced sequences demonstrated no added value. CONCLUSION: Most
      incidental pancreatic cystic lesions did not demonstrate change during follow-up.
      The addition of gadolinium-enhanced-sequences had no added-value for risk
      assignment on serial follow-up. KEY POINTS: Significant growth of pancreatic
      cysts occurred in a minority of patients only. No lesion <2 cm demonstrated any
      change during the first year of follow-up. Intra-observer agreement between MR
      pancreatic protocols with and without gadolinium was excellent. Gadolinium
      application had limited value for follow-up of asymptomatic pancreatic cystic
      lesions.

PMID- 24569850
TI  - Geometric thermal phase diagrams for studying the thermal dynamic stability of
      hollow gold nanoballs at different temperatures.
AB  - Thermal stability is one of the main concerns for the synthesis of hollow
      nanoparticles. In this work, molecular dynamics simulation gave an insight into
      the atomic reconstruction and energy evolution during the collapse of hollow gold
      nanoballs, based on which a mechanism was proposed. The stability was found to
      depend on temperature, its wall thickness and aspect ratio to a great extent. The
      relationship among these three factors was revealed in geometric thermal phase
      diagrams (GTPDs). The GTPDs were studied theoretically, and the boundary between
      different stability regions can be fitted and calculated. Therefore, the GTPDs at
      different temperatures can be deduced and used as a guide for hollow structure
      synthesis. 

PMID- 24569847
TI  - Reduction of gibberellin by low temperature disrupts pollen development in rice.
AB  - Microsporogenesis in rice (Oryza sativa) plants is susceptible to moderate low
      temperature (LT; approximately 19 degrees C) that disrupts pollen development and
      causes severe reductions in grain yields. Although considerable research has been
      invested in the study of cool-temperature injury, a full understanding of the
      molecular mechanism has not been achieved. Here, we show that endogenous levels
      of the bioactive gibberellins (GAs) GA4 and GA7, and expression levels of the GA
      biosynthesis genes GA20ox3 and GA3ox1, decrease in the developing anthers by
      exposure to LT. By contrast, the levels of precursor GA12 were higher in response
      to LT. In addition, the expression of the dehydration-responsive element-binding
      protein DREB2B and SLENDER RICE1 (SLR1)/DELLA was up-regulated in response to LT.
      Mutants involved in GA biosynthetic and response pathways were hypersensitive to
      LT stress, including the semidwarf mutants sd1 and d35, the gain-of-function
      mutant slr1-d, and gibberellin insensitive dwarf1. The reduction in the number of
      sporogenous cells and the abnormal enlargement of tapetal cells occurred most
      severely in the GA-insensitive mutant. Application of exogenous GA significantly
      reversed the male sterility caused by LT, and simultaneous application of
      exogenous GA with sucrose substantially improved the extent of normal pollen
      development. Modern rice varieties carrying the sd1 mutation are widely
      cultivated, and the sd1 mutation is considered one of the greatest achievements
      of the Green Revolution. The protective strategy achieved by our work may help
      sustain steady yields of rice under global climate change. 

PMID- 24569852
TI  - The need to eliminate commercial conflicts of interest from medicine.

PMID- 24569854
TI  - The mechanism of the NHC catalyzed aza-Morita-Baylis-Hillman reaction: insights
      into a new substrate-catalyzed bimolecular pathway.
AB  - The first mechanistic study on the NHC-catalyzed aza-MBH reaction between
      cyclopentenone and N-mesylbenzaldimine using density functional theory reveals
      that a bimolecular mechanism, involving two molecules of benzaldimine in the
      proton transfer, is energetically more preferred over the conventional direct
      proton transfer. 

PMID- 24569855
TI  - A demonstration of biofiltration for VOC removal in petrochemical industries.
AB  - A biotrickling filter demo has been set up in a petrochemical factory in Sinopec
      Group for about 10 months with a maximum inlet gas flow rate of 3000 m3 h(-1).
      The purpose of this project is to assess the ability of the biotrickling filter
      to remove hardly biodegradable VOCs such as benzene, toluene and xylene which are
      recalcitrant and poorly water soluble and commonly found in petrochemical
      factories. Light-weight hollow ceramic balls (Phi 5-8 cm) were used as the
      packing media treated with large amounts of circulating water (2.4 m3 m(-2) h(
      1)) added with bacterial species. The controlled empty bed retention time (EBRT)
      of 240 s is a key parameter for reaching a removal efficiency of 95% for benzene,
      toluene, xylene, and 90% for total hydrocarbons. The demo has been successfully
      adopted and practically applied in waste air treatments in many petrochemical
      industries for about two years. The net inlet concentrations of benzene, toluene
      and xylene were varied from 0.5 to 3 g m(-3). The biofiltration process is highly
      efficient for the removal of hydrophobic and recalcitrant VOCs with various
      concentrations from the petrochemical factories. The SEM analysis of the
      bacterial community in the BTF during VOC removal showed that Pseudomonas putida
      and Klebsiella sp. phylum were dominant and shutdown periods could play a role in
      forming the community structural differences and leading to the changes of
      removal efficiencies.

PMID- 24569853
TI  - A gradual depth-dependent change in connectivity features of supragranular
      pyramidal cells in rat barrel cortex.
AB  - Recent experimental evidence suggests a finer genetic, structural and functional
      subdivision of the layers which form a cortical column. The classical layer
      II/III (LII/III) of rodent neocortex integrates ascending sensory information
      with contextual cortical information for behavioral read-out. We systematically
      investigated to which extent regular-spiking supragranular pyramidal neurons,
      located at different depths within the cortex, show different input-output
      connectivity patterns. Combining glutamate uncaging with whole-cell recordings
      and biocytin filling, we revealed a novel cellular organization of LII/III: (1)
      "Lower LII/III" pyramidal cells receive a very strong excitatory input from
      lemniscal LIV and much fewer inputs from paralemniscal LVa. They project to all
      layers of the home column, including a feedback projection to LIV, whereas
      transcolumnar projections are relatively sparse. (2) "Upper LII/III" pyramidal
      cells also receive their strongest input from LIV, but in addition, a very strong
      and dense excitatory input from LVa. They project extensively to LII/III as well
      as LVa and Vb of their home and neighboring columns. (3) "Middle LII/III"
      pyramidal cell shows an intermediate connectivity phenotype that stands in many
      ways in between the features described for lower versus upper LII/III. "Lower
      LII/III" intracolumnarly segregates and transcolumnarly integrates lemniscal
      information, whereas "upper LII/III" seems to integrate lemniscal with
      paralemniscal information. This suggests a fine-grained functional subdivision of
      the supragranular compartment containing multiple circuits without any obvious
      cytoarchitectonic, other structural or functional correlate of a laminar border
      in rodent barrel cortex. 

PMID- 24569857
TI  - An investigation of genetic counselors' testing recommendations: pedigree
      analysis and the use of multiplex breast cancer panel testing.
AB  - Genetic testing recommendations for hereditary breast and ovarian cancer involve
      pedigree analysis and consultation of testing guidelines. The testing landscape
      for hereditary cancer syndromes is shifting as multiplex panel tests become more
      widely integrated into clinical practice. The purpose of the current study was to
      assess how genetic counselors utilize pedigrees to make recommendations for
      genetic testing, to determine consistency of these recommendations with National
      Comprehensive Cancer Network (NCCN) Guidelines and to explore current use of
      multiplex panel testing. Sixty-nine genetic counselors were recruited through the
      National Society of Genetic Counselors Cancer Special Interest Group's Discussion
      Forum. Participation involved pedigree analysis and completion of an online
      questionnaire assessing testing recommendations and use of multiplex panel
      testing. Pedigree analysis and test recommendations were scored for consistency
      with NCCN guidelines. The average score was 12.83/15 indicating strong
      consistency with NCCN guidelines. Participants were more likely to consider
      multiplex testing when pedigrees demonstrated highly penetrant dominant
      inheritance but were not indicative of a particular syndrome. Participant
      concerns about multiplex panel testing include limited guidelines for both
      testing eligibility and medical management. This study demonstrates high
      utilization of pedigree analysis and raises new questions about its use in
      multiplex genetic testing. 

PMID- 24569856
TI  - Analysis of acquired resistance to metronomic oral topotecan chemotherapy plus
      pazopanib after prolonged preclinical potent responsiveness in advanced ovarian
      cancer.
AB  - An alternative or follow-up adjunct to conventional maximum tolerated dose (MTD)
      chemotherapy now in advanced phase III clinical trial assessment is metronomic
      chemotherapy--the close regular administration of low doses of drug with no
      prolonged breaks. A number of preclinical studies have shown metronomic
      chemotherapy can cause long term survival of mice with advanced cancer, including
      metastatic disease, in the absence of overt toxicity, especially when combined
      with targeted antiangiogenic drugs. However, similar to MTD chemotherapy acquired
      resistance eventually develops, the basis of which is unknown. Using a
      preclinical model of advanced human ovarian (SKOV-3-13) cancer in SCID mice, we
      show that acquired resistance can develop after terminating prolonged (over 3
      months) successful therapy utilizing daily oral metronomic topotecan plus
      pazopanib, an oral antiangiogenic tyrosine kinase inhibitor (TKI). Two resistant
      sublines were isolated from a single mouse, one from a solid tumor (called KH092
      7SD, referred to as 7SD) and another from ascites tumor cells (called KH092-7AS,
      referred to as 7AS). Using these sublines we show acquired resistance to the
      combination treatment is due to tumor cell alterations that confer relative
      refractoriness to topotecan. The resistant phenotype is heritable, associated
      with reduced cellular uptake of topotecan and could not be reversed by switching
      to MTD topotecan or to another topoisomerase-1 inhibitor, CPT-11, given either in
      a metronomic or MTD manner nor switching to another antiangiogenic drug, e.g. the
      anti-VEGFR-2 antibody, DC101, or another TKI, sunitinib. Thus, in this case cross
      resistance seems to exist between MTD and metronomic topotecan, the basis of
      which is unknown. However, gene expression profiling revealed several potential
      genes that are stably upregulated in the resistant lines, that previously have
      been implicated in resistance to various chemotherapy drugs, and which,
      therefore, may contribute to the drug resistant phenotype.

PMID- 24569859
TI  - Deciphering the "chemical" nature of the exotic isotopes of hydrogen by the MC
      QTAIM analysis: the positively charged muon and the muonic helium as new members
      of the periodic table.
AB  - This report is a primarily survey on the chemical nature of some exotic species
      containing the positively charged muon and the muonic helium, i.e., the
      negatively charged muon plus helium nucleus, as exotic isotopes of hydrogen,
      using the newly developed multi-component quantum theory of atoms in molecules
      (MC-QTAIM) analysis, employing ab initio non-Born-Oppenhiemer wavefunctions.
      Accordingly, the "atoms in molecules" analysis performed on various asymmetric
      exotic isotopomers of the hydrogen molecule, recently detected experimentally
      [Science, 2011, 331, 448], demonstrates that both the exotic isotopes are capable
      of forming atoms in molecules and retaining the identity of hydrogen atoms.
      Various derived properties of atomic basins containing the muonic helium cast no
      doubt that apart from its short life time, it is a heavier isotope of hydrogen
      while the properties of basins containing the positively charged muon are more
      remote from those of the orthodox hydrogen basins, capable of appreciable
      donation of electrons as well as large charge polarization. However, with some
      tolerance, they may also be categorized as hydrogen basins though with a smaller
      electronegativity. All in all, the present study also clearly demonstrates that
      the MC-QTAIM analysis is an efficient approach to decipher the chemical nature of
      species containing exotic constituents, which are difficult to elucidate by
      experimental and/or alternative theoretical schemes. 

PMID- 24569858
TI  - An exploration of genetic counselors' needs and experiences with prenatal
      chromosomal microarray testing.
AB  - Because of the higher yield over traditional chromosomal analysis, chromosomal
      microarray analysis (CMA) is being used increasingly in prenatal diagnosis.
      Unfortunately, the clinical implication of many copy number variants found on
      prenatal CMA is uncertain, complicating genetic counseling. Recognizing that
      uncertain results will be encountered frequently as more of the genome is assayed
      prenatally, we set out to understand the experiences and needs of genetic
      counselors when counseling patients about uncertain prenatal microarray results,
      their comfort with various aspects of prenatal genetic counseling, and their
      interest in additional education and training about prenatal microarray testing.
      We first interviewed 10 genetic counselors about their experiences of providing
      pre- and post-test genetic counseling about prenatal CMA. Based on the findings
      from the counselor interviews, we developed items for a survey to assess the
      prevalence of genetic counselors' attitudes towards, experience and comfort with,
      and educational needs regarding prenatal CMA. Based on surveys completed by 193
      prenatal genetic counselors, we found that when there is an uncertain CMA result,
      only 59% would be comfortable providing genetic counseling and only 43% would be
      comfortable helping a patient make a decision about pregnancy termination. Being
      less comfortable was associated with seeing fewer patients having prenatal CMA
      testing. Respondents expressed a high degree of interest in additional education
      about prenatal CMA and counseling about uncertain results. Further genetic
      counselor education and training aimed at improving counselors' personal comfort
      with uncertain results and communicating about them with patients is needed.

PMID- 24569860
TI  - Clinical assessment of a shaft screw for stabilization of the humeral condyle in
      dogs.
AB  - OBJECTIVE: To report the use of a 4.5 mm shaft screw for the management of
      humeral condylar fractures (HCF) and incomplete ossification of the humeral
      condyle (IOHC) in dogs, and to assess risk factors for complications. METHODS:
      Dogs with HCF or IOHC that were managed with a 4.5 mm shaft screw with a minimum
      follow-up of six months from surgery were included. Data from the case records
      were used to identify risk factors for complications. Long-term follow-up was
      provided by an owner questionnaire and veterinary re-examination. RESULTS: Forty
      three elbows were treated in 40 dogs (14 IOHC, 29 HCF). Minor complications were
      seen in four cases (9%) and major complications in 10 cases (23%). There were no
      statistically significant risk factors for major complication. Infection resulted
      in shaft screw removal from three IOHC cases. Four of eight IOHC cases that had a
      lateral approach had a major complication compared with zero out of six dogs that
      had a medial approach, but this difference was not significant (p = 0.085). Nine
      of 12 IOHC cases and 20/23 HCF cases had excellent or good limb use at the time
      of long-term follow-up (median of 106 weeks, range 26-227 weeks). All fractures
      healed but IOHC fissure healing was inconsistent. Fatigue failure of shaft screws
      was not seen. CLINICAL SIGNIFICANCE: The use of shaft screws for the management
      of IOHC and HCF is associated with a relatively low rate of complications
      (compared to previous reports) and a good long-term outcome.

PMID- 24569861
TI  - Influence of the core size on biexciton quantum yield of giant CdSe/CdS
      nanocrystals.
AB  - We present a systematic study of photoluminescence (PL) emission intensity and
      biexciton (BX) quantum yields (QYBX) in individual "giant" CdSe/CdS nanocrystals
      (g-NCs) as a function of g-NC core size and shell thickness. We show that g-NC
      core size significantly affects QYBX and can be utilized as an effective tuning
      parameter towards higher QYBX while keeping the total volume of the g-NC
      constant. Specifically, we observe that small-core (2.2 nm diameter) CdSe/CdS NCs
      with a volume of ~200 nm(3) (shell comprises 4 CdS monolayers) show very low
      average and maximum QYBX's of ~3 and 7%, respectively. In contrast, same-volume
      medium-core (3 nm diameter) NCs afford higher average values of ~10%, while
      QYBX's of ~30% are achieved for same-volume large-core (5.5 nm diameter) CdSe/CdS
      NCs, with some approaching ~80%. These observations underline the influence of
      the g-NC core size on the evolution of PL emissive states in multi-shell NCs.
      Moreover, our study also reveals that the use of long anneal times in the growth
      of CdS shells plays a critical role in achieving high QYBX. 

PMID- 24569866
TI  - Does aneuploidy destabilize karyotypes automatically?

PMID- 24569864
TI  - A frequent, GxxxG-mediated, transmembrane association motif is optimized for the
      formation of interhelical Calpha-H hydrogen bonds.
AB  - Carbon hydrogen bonds between Calpha-H donors and carbonyl acceptors are
      frequently observed between transmembrane helices (Calpha-H...O=C). Networks of
      these interactions occur often at helix-helix interfaces mediated by GxxxG and
      similar patterns. Calpha-H hydrogen bonds have been hypothesized to be important
      in membrane protein folding and association, but evidence that they are major
      determinants of helix association is still lacking. Here we present a
      comprehensive geometric analysis of homodimeric helices that demonstrates the
      existence of a single region in conformational space with high propensity for
      Calpha-H...O=C hydrogen bond formation. This region corresponds to the most
      frequent motif for parallel dimers, GASright, whose best-known example is
      glycophorin A. The finding suggests a causal link between the high frequency of
      occurrence of GASright and its propensity for carbon hydrogen bond formation.
      Investigation of the sequence dependency of the motif determined that Gly
      residues are required at specific positions where only Gly can act as a donor
      with its "side chain" Halpha. Gly also reduces the steric barrier for non-Gly
      amino acids at other positions to act as Calpha donors, promoting the formation
      of cooperative hydrogen bonding networks. These findings offer a structural
      rationale for the occurrence of GxxxG patterns at the GASright interface. The
      analysis identified the conformational space and the sequence requirement of
      Calpha-H...O=C mediated motifs; we took advantage of these results to develop a
      structural prediction method. The resulting program, CATM, predicts ab initio the
      known high-resolution structures of homodimeric GASright motifs at near-atomic
      level. 

PMID- 24569863
TI  - Elevated hepatic 11beta-hydroxysteroid dehydrogenase type 1 induces insulin
      resistance in uremia.
AB  - Insulin resistance and associated metabolic sequelae are common in chronic kidney
      disease (CKD) and are positively and independently associated with increased
      cardiovascular mortality. However, the pathogenesis has yet to be fully
      elucidated. 11beta-Hydroxysteroid dehydrogenase type 1 (11betaHSD1) catalyzes
      intracellular regeneration of active glucocorticoids, promoting insulin
      resistance in liver and other metabolic tissues. Using two experimental rat
      models of CKD (subtotal nephrectomy and adenine diet) which show early insulin
      resistance, we found that 11betaHSD1 mRNA and protein increase in hepatic and
      adipose tissue, together with increased hepatic 11betaHSD1 activity. This was
      associated with intrahepatic but not circulating glucocorticoid excess, and
      increased hepatic gluconeogenesis and lipogenesis. Oral administration of the
      11betaHSD inhibitor carbenoxolone to uremic rats for 2 wk improved glucose
      tolerance and insulin sensitivity, improved insulin signaling, and reduced
      hepatic expression of gluconeogenic and lipogenic genes. Furthermore, 11betaHSD1(
      /-) mice and rats treated with a specific 11betaHSD1 inhibitor (UE2316) were
      protected from metabolic disturbances despite similar renal dysfunction following
      adenine experimental uremia. Therefore, we demonstrate that elevated hepatic
      11betaHSD1 is an important contributor to early insulin resistance and
      dyslipidemia in uremia. Specific 11betaHSD1 inhibitors potentially represent a
      novel therapeutic approach for management of insulin resistance in patients with
      CKD. 

PMID- 24569867
TI  - Microclimate is integral to the modeling of plant responses to macroclimate.

PMID- 24569869
TI  - Influence of urbanicity and county characteristics on the association between
      ozone and asthma emergency department visits in North Carolina.
AB  - BACKGROUND: Air pollution epidemiologic studies, often conducted in large
      metropolitan areas because of proximity to regulatory monitors, are limited in
      their ability to examine potential associations between air pollution exposures
      and health effects in rural locations. METHODS: Using a time-stratified case
      crossover framework, we examined associations between asthma emergency department
      (ED) visits in North Carolina (2006-2008), collected by a surveillance system,
      and short-term ozone (O3) exposures using predicted concentrations from the
      Community Multiscale Air Quality (CMAQ) model. We estimated associations by
      county groupings based on four urbanicity classifications (representative of
      county size and urban proximity) and county health. RESULTS: O3 was associated
      with asthma ED visits in all-year and warm season (April-October) analyses [odds
      ratio (OR) = 1.019; 95% CI: 0.998, 1.040; OR = 1.020; 95% CI: 0.997, 1.044,
      respectively, for a 20-ppb increase in lag 0-2 days O3]. The association was
      strongest in Less Urbanized counties, with no evidence of a positive association
      in Rural counties. Associations were similar when adjusted for fine particulate
      matter in copollutant models. Associations were stronger for children (5-17 years
      of age) compared with other age groups, and for individuals living in counties
      identified with poorer health status compared with counties that had the highest
      health rankings, although estimated associations for these subgroups had larger
      uncertainty. CONCLUSIONS: Associations between short-term O3 exposures and asthma
      ED visits differed by overall county health and urbanicity, with stronger
      associations in Less Urbanized counties, and no positive association in Rural
      counties. Results also suggest that children are at increased risk of O3-related
      respiratory effects.

PMID- 24569870
TI  - Rare disease registries: an initiative to establish vasculitis registry in
      Poland.

PMID- 24569871
TI  - Spinal cord stimulation for heart failure: preclinical studies to determine
      optimal stimulation parameters for clinical efficacy.
AB  - Spinal cord stimulation with implantable devices has been used worldwide for
      decades to treat regional pain conditions and cardiac angina refractory to
      conventional therapies. Preclinical studies with spinal cord stimulation in
      experimental animal models of heart disease have described interesting effects on
      cardiac and autonomic nervous system physiology. In canine and porcine animals
      with failing hearts, spinal cord stimulation reverses left ventricular dilation
      and improves cardiac function, while suppressing the prevalence of cardiac
      arrhythmias. In this paper, we present further canine studies that determined the
      optimal site and intensity of spinal cord stimulation that produced the most
      robust and beneficial clinical response in heart failure animals. We then explore
      and discuss the clinically relevant aspects and potential impediments that may be
      encountered in translating spinal cord stimulation to human patients with
      advanced cardiac disease. 

PMID- 24569868
TI  - Nitrogen removal via the nitrite pathway during wastewater co-treatment with
      ammonia-rich landfill leachates in a sequencing batch reactor.
AB  - The biological treatment of ammonia-rich landfill leachates due to an inadequate
      C to N ratio requires expensive supplementation of carbon from an external carbon
      source. In an effort to reduce treatment costs, the objective of the study was to
      determine the feasibility of nitrogen removal via the nitrite pathway during
      landfill leachate co-treatment with municipal wastewater. Initially, the
      laboratory-scale sequencing batch reactor (SBR) was inoculated with nitrifying
      activated sludge and fed only raw municipal wastewater (RWW) during a start-up
      period of 9 weeks. Then, in the co-treatment period, consisting of the next 17
      weeks, the system was fed a mixture of RWW and an increasing quantity of landfill
      leachates (from 1 to 10% by volume). The results indicate that landfill leachate
      addition of up to 10% (by volume) influenced the effluent quality, except for
      BOD5. During the experiment, a positive correlation (r(2) = 0.908) between
      ammonia load in the influent and nitrite in the effluent was observed, suggesting
      that the second step of nitrification was partially inhibited. The partial
      nitrification (PN) was also confirmed by fluorescence in situ hybridisation
      (FISH) analysis of nitrifying bacteria. Nitrogen removal via the nitrite pathway
      was observed when the oxygen concentration ranged from 0.5 to 1.5 mg O2/dm(3) and
      free ammonia (FA) ranged from 2.01 to 35.86 mg N-NH3/dm(3) in the aerobic phase.
      Increasing ammonia load in wastewater influent was also correlated with an
      increasing amount of total nitrogen (TN) in the effluent, which suggested
      insufficient amounts of assimilable organic carbon to complete denitrification.
      Because nitrogen removal via the nitrite pathway is beneficial for carbon-limited
      and highly ammonia-loaded mixtures, obtaining PN can lead to a reduction in the
      external carbon source needed to support denitrification.

PMID- 24569873
TI  - Aromatherapy for dementia.
AB  - BACKGROUND: Complementary therapy has received great interest within the field of
      dementia treatment and the use of aromatherapy and essential oils is increasing.
      In a growing population where the majority of patients are treated by US Food and
      Drug Administration (FDA)-approved drugs, the efficacy of treatment is short term
      and accompanied by negative side effects. Utilisation of complimentary therapies
      in dementia care settings presents as one of few options that are attractive to
      practitioners and families as patients often have reduced insight and ability to
      verbally communicate adverse reactions. Amongst the most distressing features of
      dementia are the behavioural and psychological symptoms. Addressing this facet
      has received particular interest in aromatherapy trials, with a shift in focus
      from reducing cognitive dysfunction to the reduction of behavioural and
      psychological symptoms in dementia. OBJECTIVES: To assess the efficacy of
      aromatherapy as an intervention for people with dementia. SEARCH METHODS: ALOIS,
      the Cochrane Dementia and Cognitive Improvement Group Specialized Register, was
      searched on 26 November 2012 and 20 January 2013 using the terms: aromatherapy,
      lemon, lavender, rose, aroma, alternative therapies, complementary therapies,
      essential oils. SELECTION CRITERIA: All relevant randomised controlled trials
      were considered. A minimum length of a trial and requirements for follow-up were
      not included, and participants in included studies had a diagnosis of dementia of
      any type and severity. The review considered all trials using fragrance from
      plants defined as aromatherapy as an intervention with people with dementia and
      all relevant outcomes were considered. DATA COLLECTION AND ANALYSIS: Titles and
      abstracts extracted by the searches were screened for their eligibility for
      potential inclusion in the review. For Burns 2011, continuous outcomes were
      estimated as the mean difference between groups and its 95% confidence interval
      using a fixed-effect model. For Ballard 2002, analysis of co-variance was used
      for all outcomes, with the nursing home being treated as a random effect. MAIN
      RESULTS: Seven studies with 428 participants were included in this review; only
      two of these had published usable results. Individual patient data were obtained
      from one trial (Ballard 2002) and additional analyses performed. The additional
      analyses conducted using individual patient data from Ballard 2002 revealed a
      statistically significant treatment effect in favour of the aromatherapy
      intervention on measures of agitation (n = 71, MD -11.1, 95% CI -19.9 to -2.2)
      and behavioural symptoms (n = 71, MD -15.8, 95% CI -24.4 to -7.2). Burns 2011,
      however, found no difference in agitation (n = 63, MD 0.00, 95% CI -1.36 to
      1.36), behavioural symptoms (n = 63, MD 2.80, 95% CI -5.84 to 11.44), activities
      of daily living (n = 63, MD -0.50, 95% CI -1.79 to 0.79) and quality of life (n =
      63, MD 19.00, 95% CI -23.12 to 61.12). Burns 2011 and Fu 2013 found no difference
      in adverse effects (n = 124, RR 0.97, 95% CI 0.15 to 6.46) when aromatherapy was
      compared to placebo. AUTHORS' CONCLUSIONS: The benefits of aromatherapy for
      people with dementia are equivocal from the seven trials included in this review.
      It is important to note there were several methodological difficulties with the
      included studies. More well-designed, large-scale randomised controlled trials
      are needed before clear conclusions can be drawn regarding the effectiveness of
      aromatherapy for dementia. Additionally, several issues need to be addressed,
      such as whether different aromatherapy interventions are comparable and the
      possibility that outcomes may vary for different types of dementia.

PMID- 24569872
TI  - Migration inhibitory factor enhances inflammation via CD74 in cartilage end
      plates with Modic type 1 changes on MRI.
AB  - BACKGROUND: Type 1 Modic changes are characterized by edema, vascularization, and
      inflammation, which lead to intervertebral disc degeneration. Macrophage
      migration inhibitory factor (MIF) is a proinflammatory cytokine closely related
      to the inflammatory cytokines detected in degenerative intervertebral disc
      tissues. However, the existence and role of MIF and its receptor CD74 in
      intervertebral disc degeneration have not been elucidated. QUESTIONS/PURPOSES: We
      asked whether (1) MIF and its receptor CD74 are expressed in cartilage end plates
      with Type 1 Modic changes, (2) MIF is associated with cartilage end plate
      degeneration, (3) the MIF antagonist (S, R)-3(4-hydroxyphenyl)-4, 5-dihydro-5
      isoxazole acetic acid methyl ester (ISO-1) suppresses MIF-induced inflammatory
      cytokine release, and (4) inflammatory cytokines are released by cartilage end
      plate chondrocytes via CD74 by activating the CD74 antibody (CD74Ab). METHODS: We
      examined MIF and CD74 expression by human cartilage end plate chondrocytes and
      tissues with Type 1 Modic changes from eight patients using
      immunocytofluorescence and immunohistochemistry. MIF production by the
      chondrocytes was assessed by ELISA and PCR. We compared cytokine release by
      chondrocytes treated with MIF in the presence or absence of exogenous ISO-1 by
      ELISA. Cytokine release by chondrocytes after treatment with CD74Ab was
      determined by ELISA. RESULTS: MIF was expressed in degenerated human cartilage
      end plate tissues and chondrocytes. Lipopolysaccharide and tumor necrosis factor
      alpha (TNF-alpha) upregulated MIF expression and increased MIF secretion in
      chondrocytes in a dose-dependent manner. MIF increased the secretion of IL-6, IL
      8, and prostaglandin E2 (PGE2) in a dose-dependent manner. ISO-1 reduced the
      secretion of IL-6, IL-8, and PGE2. CD74Ab activated CD74 and induced release of
      inflammatory cytokines. CONCLUSIONS: Chondrocytes in cartilage end plate with
      Type 1 Modic changes express MIF and its receptor CD74. MIF might promote the
      inflammatory response through CD74. MIF-induced cytokine release appears to be
      suppressed by ISO-1, and CD74Ab could induce cytokine release. CLINICAL
      RELEVANCE: The MIF/CD74 pathway may represent a crucial target for treating disc
      degeneration since inhibiting the function of MIF with its antagonist ISO-1 can
      reduce MIF-induced inflammation and exert potent therapeutic effects.

PMID- 24569874
TI  - Insulin elicits a ROS-activated and an IP3-dependent Ca2+ release, which both
      impinge on GLUT4 translocation.
AB  - Insulin signaling includes generation of low levels of H2O2; however, its origin
      and contribution to insulin-stimulated glucose transport are unknown. We tested
      the impact of H2O2 on insulin-dependent glucose transport and GLUT4 translocation
      in skeletal muscle cells. H2O2 increased the translocation of GLUT4 with an
      exofacial Myc-epitope tag between the first and second transmembrane domains
      (GLUT4myc), an effect additive to that of insulin. The anti-oxidants N-acetyl L
      cysteine and Trolox, the p47(phox)-NOX2 NADPH oxidase inhibitory peptide gp91-ds
      tat or p47(phox) knockdown each reduced insulin-dependent GLUT4myc translocation.
      Importantly, gp91-ds-tat suppressed insulin-dependent H2O2 production. A
      ryanodine receptor (RyR) channel agonist stimulated GLUT4myc translocation and
      insulin stimulated RyR1-mediated Ca(2+) release by promoting RyR1 S
      glutathionylation. This pathway acts in parallel to insulin-mediated stimulation
      of inositol-1,4,5-trisphosphate (IP3)-activated Ca(2+) channels, in response to
      activation of phosphatidylinositol 3-kinase and its downstream target
      phospholipase C, resulting in Ca(2+) transfer to the mitochondria. An inhibitor
      of IP3 receptors, Xestospongin B, reduced both insulin-dependent IP3 production
      and GLUT4myc translocation. We propose that, in addition to the canonical
      alpha,beta phosphatidylinositol 3-kinase to Akt pathway, insulin engages both RyR
      mediated Ca(2+) release and IP3-receptor-mediated mitochondrial Ca(2+) uptake,
      and that these signals jointly stimulate glucose uptake.

PMID- 24569875
TI  - Notch signaling regulates the differentiation of neural crest from human
      pluripotent stem cells.
AB  - Neural crest cells are specified at the border between the neural plate and the
      epiderm. They are capable of differentiating into various somatic cell types,
      including craniofacial and peripheral nerve tissues. Notch signaling plays
      important roles during neurogenesis; however, its function during human neural
      crest development is poorly understood. Here, we generated self-renewing
      premigratory neural-crest-like cells (pNCCs) from human pluripotent stem cells
      (hPSCs) and investigated the roles of Notch signaling during neural crest
      differentiation. pNCCs expressed various neural-crest-specifier genes, including
      SLUG (also known as SNAI2), SOX10 and TWIST1, and were able to differentiate into
      most neural crest derivatives. Blocking Notch signaling during the pNCC
      differentiation suppressed the expression of neural-crest-specifier genes. By
      contrast, ectopic expression of activated Notch1 intracellular domain (NICD1)
      augmented the expression of neural-crest-specifier genes, and NICD1 was found to
      bind to their promoter regions. Notch activity was also required for the
      maintenance of the premigratory neural crest state, and the suppression of Notch
      signaling led to the generation of neural-crest-derived neurons. Taken together,
      we provide a protocol for the generation of pNCCs and show that Notch signaling
      regulates the formation, migration and differentiation of neural crest from
      hPSCs.

PMID- 24569876
TI  - The polysome-associated proteins Scp160 and Bfr1 prevent P body formation under
      normal growth conditions.
AB  - Numerous mRNAs are degraded in processing bodies (P bodies) in Saccharomyces
      cerevisiae. In logarithmically growing cells, only 0-1 P bodies per cell are
      detectable. However, the number and appearance of P bodies change once the cell
      encounters stress. Here, we show that the polysome-associated mRNA-binding
      protein Scp160 interacts with P body components, such as the decapping protein
      Dcp2 and the scaffold protein Pat1, presumably, on polysomes. Loss of either
      Scp160 or its interaction partner Bfr1 caused the formation of Dcp2-positive
      structures. These Dcp2-positive foci contained mRNA, because their formation was
      inhibited by the presence of cycloheximide. In addition, Scp160 was required for
      proper P body formation because only a subset of bona fide P body components
      could assemble into the Dcp2-positive foci in Deltascp160 cells. In either
      Deltabfr1 or Deltascp160 cells, P body formation was uncoupled from translational
      attenuation as the polysome profile remained unchanged. Collectively, our data
      suggest that Bfr1 and Scp160 prevent P body formation under normal growth
      conditions.

PMID- 24569879
TI  - Consequences of the disease-related L78R mutation for dimerization and activity
      of STAT3.
AB  - Signal transducer and activator of transcription 3 (STAT3) is a transcription
      factor that is centrally involved in diverse processes including haematopoiesis,
      immunity and cancer progression. In response to cytokine stimulation, STAT3 is
      activated through phosphorylation of a single tyrosine residue. The
      phosphorylated STAT3 dimers are stabilized by intermolecular interactions between
      SH2 domains and phosphotyrosine. These activated dimers accumulate in the nucleus
      and bind to specific DNA sequences, resulting in target gene expression. We
      analysed and compared the structural organizations of the unphosphorylated latent
      and phosphorylated activated STAT3 dimers using Forster resonance energy transfer
      (FRET) in fixed and living cells. The latent dimers are stabilized by homotypic
      interactions between the N-terminal domains. A somatic mutation (L78R) found in
      inflammatory hepatocellular adenoma (IHCA), which is located in the N-terminal
      domain of STAT3 disturbs latent dimer formation. Applying intramolecular FRET, we
      verify a functional role of the SH2 domain in latent dimer formation suggesting
      that the protomers in the latent STAT3 dimer are in a parallel orientation,
      similar to activated STAT3 dimers but different from the antiparallel orientation
      of the latent dimers of STAT1 and STAT5. Our findings reveal unique structural
      characteristics of STAT3 within the STAT family and contribute to the
      understanding of the L78R mutation found in IHCA.

PMID- 24569877
TI  - Fam118B, a newly identified component of Cajal bodies, is required for Cajal body
      formation, snRNP biogenesis and cell viability.
AB  - Cajal bodies are specialized and dynamic compartments in the nucleus that are
      involved in the biogenesis of small nuclear ribonucleoproteins (snRNPs). Because
      of the dynamic and varied roles of Cajal bodies, it is of great interest to
      identify the components of Cajal bodies to better understand their functions. We
      performed a genome-wide screen to identify proteins that colocalize with coilin,
      the marker protein of Cajal bodies. In this study, we identified and
      characterized Fam118B as a newly discovered component of Cajal bodies. Fam118B is
      widely expressed in a variety of cell lines derived from various origins.
      Overexpression of Fam118B changes the canonical morphology of Cajal bodies,
      whereas depletion of Fam118B disrupts the localization of components of Cajal
      bodies, including coilin, the survival of motor neuron protein (SMN) and the Sm
      protein D1 (SmD1, also known as SNRPD1). Moreover, depletion of Fam118B reduces
      splicing capacity and inhibits cell proliferation. In addition, Fam118B
      associates with coilin and SMN proteins. Fam118B depletion reduces symmetric
      dimethylarginine modification of SmD1, which in turn diminishes the binding of
      SMN to this Sm protein. Taken together, these data indicate that Fam118B, by
      regulating SmD1 symmetric dimethylarginine modification, plays an important role
      in Cajal body formation, snRNP biogenesis and cell viability.

PMID- 24569878
TI  - The requirement for Cdc48/p97 in nuclear protein quality control degradation
      depends on the substrate and correlates with substrate insolubility.
AB  - Cdc48, known as p97 or valosin-containing protein (VCP) in mammals, is an
      abundant AAA-ATPase that is essential for many ubiquitin-dependent processes. One
      well-documented role for Cdc48 is in facilitating the delivery of ubiquitylated
      misfolded endoplasmic reticulum proteins to the proteasome for degradation. By
      contrast, the role for Cdc48 in misfolded protein degradation in the nucleus is
      unknown. In the budding yeast Saccharomyces cerevisiae, degradation of misfolded
      proteins in the nucleus is primarily mediated by the nuclear-localized ubiquitin
      protein ligase San1, which ubiquitylates misfolded nuclear proteins for
      proteasomal degradation. Here, we find that, although Cdc48 is involved in the
      degradation of some San1 substrates, it is not universally required. The
      difference in the requirement for Cdc48 correlates with the insolubility of the
      San1 substrate. The more insoluble the substrate, the more its degradation
      requires Cdc48. Expression of Cdc48-dependent San1 substrates in mutant cdc48
      cells results in increased substrate insolubility, larger inclusion formation and
      reduced cell viability. Substrate ubiquitylation is increased in mutant cdc48
      cells, suggesting that Cdc48 functions downstream of San1. Taken together, we
      propose that Cdc48 acts, in part, to maintain the solubility or reverse the
      aggregation of insoluble misfolded proteins prior to their proteasomal
      degradation.

PMID- 24569880
TI  - Phosphorylation of the retinoic acid receptor RARgamma2 is crucial for the
      neuronal differentiation of mouse embryonic stem cells.
AB  - Retinoic acid (RA) plays key roles in cell differentiation and growth arrest by
      activating nuclear RA receptors (RARs) (alpha, beta and gamma), which are ligand
      dependent transcription factors. RARs are also phosphorylated in response to RA.
      Here, we investigated the in vivo relevance of the phosphorylation of RARs during
      RA-induced neuronal differentiation of mouse embryonic stem cells (mESCs). Using
      ESCs where the genes encoding each RAR subtype had been inactivated, and stable
      rescue lines expressing RARs mutated in phospho-acceptor sites, we show that RA
      induced neuronal differentiation involves RARgamma2 and requires RARgamma2
      phosphorylation. By gene expression profiling, we found that the phosphorylated
      form of RARgamma2 regulates a small subset of genes through binding an unusual RA
      response element consisting of two direct repeats with a seven-base-pair spacer.
      These new findings suggest an important role for RARgamma phosphorylation during
      cell differentiation and pave the way for further investigations during embryonic
      development.

PMID- 24569881
TI  - Tuning the electrical properties of the heart by differential trafficking of KATP
      ion channel complexes.
AB  - The copy number of membrane proteins at the cell surface is tightly regulated.
      Many ion channels and receptors present retrieval motifs to COPI vesicle coats
      and are retained in the early secretory pathway. In some cases, the interaction
      with COPI is prevented by binding to 14-3-3 proteins. However, the functional
      significance of this antagonism between COPI and 14-3-3 in terminally
      differentiated cells is unknown. Here, we show that ATP-sensitive K(+) (KATP)
      channels, which are composed of Kir6.2 and SUR1 subunits, are stalled in the
      Golgi complex of ventricular, but not atrial, cardiomyocytes. Upon sustained beta
      adrenergic stimulation, which leads to activation of protein kinase A (PKA), SUR1
      containing channels reach the plasma membrane of ventricular cells. We show that
      PKA-dependent phosphorylation of the C-terminus of Kir6.2 decreases binding to
      COPI and, thereby, silences the arginine-based retrieval signal. Thus, activation
      of the sympathetic nervous system releases this population of KATP channels from
      storage in the Golgi and, hence, might facilitate the adaptive response to
      metabolic challenges.

PMID- 24569882
TI  - The p75 neurotrophin receptor evades the endolysosomal route in neuronal cells,
      favouring multivesicular bodies specialised for exosomal release.
AB  - The p75 neurotrophin receptor (p75, also known as NGFR) is a multifaceted
      signalling receptor that regulates neuronal physiology, including neurite
      outgrowth, and survival and death decisions. A key cellular aspect regulating
      neurotrophin signalling is the intracellular trafficking of their receptors;
      however, the post-endocytic trafficking of p75 is poorly defined. We used
      sympathetic neurons and rat PC12 cells to study the mechanism of internalisation
      and post-endocytic trafficking of p75. We found that p75 internalisation depended
      on the clathrin adaptor protein AP2 and on dynamin. More surprisingly, p75 evaded
      the lysosomal route at the level of the early endosome, instead accumulating in
      two different types of endosomes, Rab11-positive endosomes and multivesicular
      bodies (MVBs) positive for CD63, a marker of the exosomal pathway. Consistently,
      depolarisation by KCl induced the liberation of previously endocytosed full
      length p75 into the extracellular medium in exosomes. Thus, p75 defines a
      subpopulation of MVBs that does not mature to lysosomes and is available for
      exosomal release by neuronal cells.

PMID- 24569883
TI  - Identification of an immune-regulated phagosomal Rab cascade in macrophages.
AB  - Interferon-gamma (IFN-gamma) has been shown to regulate phagosome trafficking and
      function in macrophages, but the molecular mechanisms involved are poorly
      understood. Here, we identify Rab20 as part of the machinery by which IFN-gamma
      controls phagosome maturation. We found that IFN-gamma stimulates the association
      of Rab20 with early phagosomes in macrophages. By using imaging of single
      phagosomes in live cells, we found that Rab20 induces an early delay in phagosome
      maturation and extends the time for which Rab5a and phosphatidylinositol 3
      phosphate (PI3P) remain associated with phagosomes. Moreover, Rab20 depletion in
      macrophages abrogates the delay in phagosome maturation induced by IFN-gamma.
      Finally, we demonstrate that Rab20 interacts with the Rab5a guanine nucleotide
      exchange factor Rabex-5 (also known as RABGEF1) and that Rab20 knockdown impairs
      the IFN-gamma-dependent recruitment of Rabex-5 and Rab5a into phagosomes. Taken
      together, here, we uncover Rab20 as a key player in the Rab cascade by which IFN
      gamma induces a delay in phagosome maturation in macrophages.

PMID- 24569884
TI  - Journal of Artificial Organs 2013: the year in review : Journal of Artificial
      Organs Editorial Committee.

PMID- 24569886
TI  - Criminal HIV exposure laws: moving forward.

PMID- 24569887
TI  - Promoting regular testing: an examination of HIV and STI testing routines and
      associated socio-demographic, behavioral and social-cognitive factors among men
      who have sex with men in New South Wales, Australia.
AB  - Human immunodeficiency virus (HIV) and sexually transmitted infections (STI)
      testing rates are amongst the highest in the world among men who have sex with
      men (MSM) in Australia. However, notable minorities have never tested and many
      MSM have not tested recently. To examine testing routines and assess covariates
      of testing, an online survey was conducted among MSM in New South Wales. Five
      hundred and eighty non-HIV positive MSM (Mean age: 29.33 years) were randomized
      to answer questions on barriers to testing for HIV or STI. One in five (20.9 %)
      non-HIV-positive participants had never tested for HIV, 27.2 % had no HIV testing
      routines, 22.8 % had a moderate HIV testing routines, and 29.1 % had strong HIV
      testing routines. Similar patterning was observed for STI testing. In
      multivariate analyses participants' knowledge, beliefs, attitudes, subjective
      norms and perceived behavioral control were moderately related to HIV and/or STI
      testing routines and some associations were specific to either HIV or STI testing
      or to particular routines. Findings highlight that multiple social-cognitive
      factors each play a role in explaining HIV and STI testing among MSM. To
      effectively promote regular testing in MSM, programs face the challenge of having
      to address a range of hurdles, rather than a few major obstacles.

PMID- 24569885
TI  - Monitoring of regional lung ventilation using electrical impedance tomography
      after cardiac surgery in infants and children.
AB  - Electrical impedance tomography (EIT) is a noninvasive method to monitor regional
      lung ventilation in infants and children without using radiation. The objective
      of this prospective study was to determine the value of EIT as an additional
      monitoring tool to assess regional lung ventilation after pediatric cardiac
      surgery for congenital heart disease in infants and children. EIT monitoring was
      performed in a prospective study comprising 30 pediatric patients who were
      mechanically ventilated after cardiac surgery. Data were analyzed off-line with
      respect to regional lung ventilation in different clinical situations. EIT data
      were correlated with respirator settings and arterial carbon dioxide (CO2)
      partial pressure in the blood. In 29 of 30 patients, regional ventilation of the
      lung could sufficiently and reliably be monitored by means of EIT. The effects of
      the transition from mechanical ventilation to spontaneous breathing after
      extubation on regional lung ventilation were studied. After extubation, a
      significant decrease of relative impedance changes was evident. In addition, a
      negative correlation of arterial CO2 partial pressure and relative impedance
      changes could be shown. EIT was sufficient to discriminate differences of
      regional lung ventilation in children and adolescents after cardiac surgery. EIT
      reliably provided additional information on regional lung ventilation in children
      after cardiac surgery. Neither chest tubes nor pacemaker wires nor the intensive
      care unit environment interfered with the application of EIT. EIT therefore may
      be used as an additional real-time monitoring tool in pediatric cardiac intensive
      care because it is noninvasive. 

PMID- 24569890
TI  - Changes to EP - Europace: focus on celluar cardiac electrophysiology and e
      cardiology.

PMID- 24569889
TI  - Carboxy-directed asymmetric hydrogenation of alpha-alkyl-alpha-aryl terminal
      olefins: highly enantioselective and chemoselective access to a chiral
      benzylmethyl center.
AB  - A carboxy-directed asymmetric hydrogenation of alpha-alkyl-alpha-aryl terminal
      olefins was developed by using a chiral spiro iridium catalyst, providing a
      highly efficient approach to the compounds with a chiral benzylmethyl center. The
      carboxy-directed hydrogenation prohibited the isomerization of the terminal
      olefins, and realized the chemoselective hydrogenation of various dienes. The
      concise enantioselective syntheses of (S)-curcudiol and (S)-curcumene were
      achieved by using this catalytic asymmetric hydrogenation as a key step.

PMID- 24569888
TI  - A study of perceived racial discrimination in Black men who have sex with men
      (MSM) and its association with healthcare utilization and HIV testing.
AB  - In HPTN 061, a study of Black men who have sex with men (MSM), we evaluated the
      association of healthcare-specific racial discrimination with healthcare
      utilization and HIV testing among 1167 HIV-negative participants. Median age was
      38 years, 41 % were uninsured, and 38 % had an annual household income <$10,000.
      Overall, 19 % reported healthcare-specific racial discrimination directed toward
      family, friend, or self; 61 % saw a healthcare provider in the previous 6 months
      and 81 % HIV tested within the past year. Healthcare-specific racial
      discrimination was positively associated with seeing a provider [adjusted odds
      ratio (AOR) = 1.4 (1.0, 2.0)] and HIV testing [AOR = 1.6 (1.1, 2.4)] suggesting
      that barriers other than racial discrimination may be driving health disparities
      related to access to medical care and HIV testing among Black MSM. These results
      contrast with previous studies, possibly due to measurement or cohort
      differences, strategies to overcome discrimination, or because of greater
      exposure to healthcare.

PMID- 24569892
TI  - Computational cardiac electrophysiology is ready for prime time.

PMID- 24569891
TI  - Current periprocedural management of ablation for atrial fibrillation in Europe:
      results of the European Heart Rhythm Association survey.
AB  - The purpose of this EP Wire survey was to assess clinical practice in
      periprocedural management of atrial fibrillation ablation. This survey is based
      on an electronic questionnaire sent to the European Heart Rhythm Association
      Research Network members. Responses were received from 78 centres in 20
      countries. The results of the survey have shown that periprocedural management is
      generally in accordance with guidelines and consensus recommendations on ablation
      for atrial fibrillation ablation, although there are some areas of variation.
      Differences between high- and low-volume centres are observed with respect to
      patient selection, antiarrhythmic drug management, and heparin bridging. 

PMID- 24569893
TI  - Pacemaker activity of the human sinoatrial node: effects of HCN4 mutations on the
      hyperpolarization-activated current.
AB  - The hyperpolarization-activated 'funny' current, If, plays an important
      modulating role in the pacemaker activity of the human sinoatrial node (SAN). If
      is carried by hyperpolarization-activated cyclic nucleotide-gated (HCN) channels,
      which are tetramers built of four HCN subunits. In human SAN, HCN4 is the most
      abundant of the four isoforms of the HCN family. Since 2003, several loss-of
      function mutations in the HCN4 gene, which encodes the HCN4 protein, or in the
      KCNE2 gene, which encodes the MiRP1 accessory beta-subunit, have been associated
      with sinus node dysfunction. Voltage-clamp experiments on HCN4 channels expressed
      in COS-7 cells, Xenopus oocytes, or HEK-293 cells have revealed changes in the
      expression and kinetics of mutant channels, but the extent to which these changes
      would affect If flowing during a human SAN action potential is unresolved. Here,
      we review the changes in expression and kinetics of HCN4 mutant channels and
      provide an overview of their effects on If during the time course of a human SAN
      action potential, both under resting conditions and upon adrenergic stimulation.
      These effects are assessed in simulated action potential clamp experiments, with
      action potentials recorded from isolated human SAN pacemaker cells as command
      potential and kinetics of If based on voltage-clamp data from these cells.
      Results from in vitro and in silico experiments show several inconsistencies with
      clinical observations, pointing to challenges for future research. 

PMID- 24569894
TI  - Recurrent intradialytic paroxysmal atrial fibrillation: hypotheses on onset
      mechanisms based on clinical data and computational analysis.
AB  - Atrial fibrillation (AF) incidence is high in end-stage renal disease (ESRD)
      patients, and haemodialysis (HD) session may induce paroxysmal AF episodes.
      Structural atrium remodelling is common in ESRD patients, moreover, HD session
      induces rapid plasma electrolytes and blood volume changes, possibly favouring
      arrhythmia onset. Therefore, HD session represents a unique model to study in
      vivo the mechanisms potentially inducing paroxysmal AF episodes. Here, we present
      the case report of a patient in which HD regularly induced paroxysmal AF. In four
      consecutive sessions, heart rate variability analysis showed a progressive
      reduction of low/high frequency ratio before the AF onset, suggesting a relative
      increase in vagal activity. Moreover, all AF episodes were preceded by a great
      increase of supraventricular ectopic beats. We applied computational modelling of
      cardiac cellular electrophysiology to these clinical findings, using plasma
      electrolyte concentrations and heart rate to simulate patient conditions at the
      beginning of HD session (pre-HD) and right before the AF onset (pre-AF), in a
      human atrial action potential model. Simulation results provided evidence of a
      slower depolarization and a shortened refractory period in pre-AF vs. pre-HD, and
      these effects were enhanced when adding acetylcholine effect. Paroxysmal AF
      episodes are induced by the presence of a trigger that acts upon a favourable
      substrate on the background of autonomic nervous system changes and in the
      described case report all these three elements were present. Starting from these
      findings, here we review the possible mechanisms leading to intradialytic AF
      onset. 

PMID- 24569895
TI  - Multiscale computational analysis of the bioelectric consequences of myocardial
      ischaemia and infarction.
AB  - Ischaemic heart disease is considered as the single most frequent cause of death,
      provoking more than 7 000 000 deaths every year worldwide. A high percentage of
      patients experience sudden cardiac death, caused in most cases by tachyarrhythmic
      mechanisms associated to myocardial ischaemia and infarction. These diseases are
      difficult to study using solely experimental means due to their complex dynamics
      and unstable nature. In the past decades, integrative computational simulation
      techniques have become a powerful tool to complement experimental and clinical
      research when trying to elucidate the intimate mechanisms of ischaemic
      electrophysiological processes and to aid the clinician in the improvement and
      optimization of therapeutic procedures. The purpose of this paper is to briefly
      review some of the multiscale computational models of myocardial ischaemia and
      infarction developed in the past 20 years, ranging from the cellular level to
      whole-heart simulations. 

PMID- 24569896
TI  - Evolution and pharmacological modulation of the arrhythmogenic wave dynamics in
      canine pulmonary vein model.
AB  - AIMS: Atrial fibrillation (AF), the commonest cardiac arrhythmia, has been
      strongly linked with arrhythmogenic sources near the pulmonary veins (PVs), but
      underlying mechanisms are not fully understood. We aim to study the generation
      and sustenance of wave sources in a model of the PV tissue. METHODS AND RESULTS:
      A previously developed biophysically detailed three-dimensional canine atrial
      model is applied. Effects of AF-induced electrical remodelling are introduced
      based on published experimental data, as changes of ion channel currents (ICaL,
      IK1, Ito, and IKur), the action potential (AP) and cell-to-cell coupling levels.
      Pharmacological effects are introduced by blocking specific ion channel currents.
      A combination of electrical heterogeneity (AP tissue gradients of 5-12 ms) and
      anisotropy (conduction velocities of 0.75-1.25 and 0.21-0.31 m/s along and
      transverse to atrial fibres) can results in the generation of wave breaks in the
      PV region. However, a long wavelength (171 mm) prevents the wave breaks from
      developing into re-entry. Electrical remodelling leads to decreases in the AP
      duration, conduction velocity and wavelength (to 49 mm), such that re-entry
      becomes sustained. Pharmacological effects on the tissue heterogeneity and
      vulnerability (to wave breaks and re-entry) are quantified to show that drugs
      that increase the wavelength and stop re-entry (IK1 and IKur blockers) can also
      increase the heterogeneity (AP gradients of 26-27 ms) and the likelihood of wave
      breaks. CONCLUSION: Biophysical modelling reveals large conduction block areas
      near the PVs, which are due to discontinuous fibre arrangement enhanced by
      electrical heterogeneity. Vulnerability to re-entry in such areas can be
      modulated by pharmacological interventions.

PMID- 24569897
TI  - Mechanistic insights into hypothermic ventricular fibrillation: the role of
      temperature and tissue size.
AB  - AIMS: Hypothermia is well known to be pro-arrhythmic, yet it has beneficial
      effects as a resuscitation therapy and valuable during intracardiac surgeries.
      Therefore, we aim to study the mechanisms that induce fibrillation during
      hypothermia. A better understanding of the complex spatiotemporal dynamics of
      heart tissue as a function of temperature will be useful in managing the benefits
      and risks of hypothermia. METHODS AND RESULTS: We perform two-dimensional
      numerical simulations by using a minimal model of cardiac action potential
      propagation fine-tuned on experimental measurements. The model includes thermal
      factors acting on the ionic currents and the gating variables to correctly
      reproduce experimentally recorded restitution curves at different temperatures.
      Simulations are implemented using WebGL, which allows long simulations to be
      performed as they run close to real time. We describe (i) why fibrillation is
      easier to induce at low temperatures, (ii) that there is a minimum size required
      for fibrillation that depends on temperature, (iii) why the frequency of
      fibrillation decreases with decreasing temperature, and (iv) that regional
      cooling may be an anti-arrhythmic therapy for small tissue sizes however it may
      be pro-arrhythmic for large tissue sizes. CONCLUSION: Using a mathematical
      cardiac cell model, we are able to reproduce experimental observations,
      quantitative experimental results, and discuss possible mechanisms and
      implications of electrophysiological changes during hypothermia.

PMID- 24569898
TI  - Arrhythmic potency of human ether-a-go-go-related gene mutations L532P and N588K
      in a computational model of human atrial myocytes.
AB  - AIMS: Human ether-a-go-go-related gene (hERG) missense mutations N588K and L532P
      are both associated with atrial fibrillation (AF). However, the underlying gain
      of-function mechanism is different. The aim of this computational study is to
      assess and understand the arrhythmogenic mechanisms of these genetic disorders on
      the cellular and tissue level as a basis for the improvement of therapeutic
      strategies. METHODS AND RESULTS: The IKr formulation of an established model of
      human atrial myocytes was adapted by using the measurement data of wild-type and
      mutant hERG channels. Restitution curves of the action potential duration and its
      slope, effective refractory period (ERP), conduction velocity, reentry wavelength
      (WL), and the vulnerable window (VW) were determined in a one-dimensional (1D)
      tissue strand. Moreover, spiral wave inducibility and rotor lifetime in a 2D
      tissue patch were evaluated. The two mutations caused an increase in IKr
      regarding both peak amplitude and current integral, whereas the duration during
      which IKr is active was decreased. The WL was reduced due to a shorter ERP.
      Spiral waves could be initiated by using mutation models as opposed to the
      control case. The frequency dependency of the VW was reversed. CONCLUSION: Both
      mutations showed an increased arrhythmogenicity due to decreased refractory time
      in combination with a more linear repolarization phase. The effects were more
      pronounced for mutation L532P than for N588K. Furthermore, spiral waves presented
      higher stability and a more regular pattern for L532P. These in silico
      investigations unveiling differences of mutations affecting the same ion channel
      may help to advance genotype-guided AF prevention and therapy strategies.

PMID- 24569899
TI  - In silico ischaemia-induced reentry at the Purkinje-ventricle interface.
AB  - AIMS: This computational modelling work illustrates the influence of
      hyperkalaemia and electrical uncoupling induced by defined ischaemia on action
      potential (AP) propagation and the incidence of reentry at the Purkinje-ventricle
      interface in mammalian hearts. METHODS AND RESULTS: Unidimensional and
      bidimensional models of the Purkinje-ventricle subsystem, including ischaemic
      conditions (defined as phase 1B) in the ventricle and an ischaemic border zone,
      were developed by altering several important electrophysiological parameters of
      the Luo-Rudy AP model of the ventricular myocyte. Purkinje electrical activity
      was modelled using the equations of DiFrancesco and Noble. Our study suggests
      that an extracellular potassium concentration [K(+)]o >14 mM and a slight
      decrease in intercellular coupling induced by ischaemia in ventricle can cause
      conduction block from Purkinje to ventricle. Under these conditions, propagation
      from ventricle to Purkinje is possible. Thus, unidirectional block (UDB) and
      reentry can result. When conditions of UDB are met, retrograde propagation with a
      long delay (320 ms) may re-excite Purkinje cells, and give rise to a reentrant
      pathway. This induced reentry may be the origin of arrhythmias observed in phase
      1B ischaemia. CONCLUSION: In a defined setting of ischaemia (phase 1B), a small
      amount of uncoupling between ventricular cells, as well as between Purkinje and
      ventricular tissue, may induce UDBs and reentry. Hyperkalaemia is also confirmed
      to be an important factor in the genesis of reentrant rhythms, since it regulates
      the range of coupling in which UDBs may be induced.

PMID- 24569902
TI  - [Not Available].

PMID- 24569900
TI  - How does beta-adrenergic signalling affect the transitions from ventricular
      tachycardia to ventricular fibrillation?
AB  - AIMS: Ventricular tachycardia (VT) and fibrillation (VF) are the most lethal
      cardiac arrhythmias. The degeneration of VT into VF is associated with the
      breakup of a spiral wave of the action potential in cardiac tissue. beta
      Adrenergic (betaAR) signalling potentiates the L-type Ca current (ICaL) faster
      than the slow delayed rectifier potassium current (IKs), which transiently
      prolongs the action potential duration (APD) and promotes early after
      depolarizations. In this study, we aimed at investigating how betaAR signalling
      affects the transition from VT to VF. METHODS AND RESULTS: We used a
      physiologically detailed computer model of the rabbit ventricular myocyte in a
      two-dimensional tissue to determine how spiral waves respond to betaAR activation
      following administration of isoproterenol. A simplified mathematical model was
      also used to investigate the underlying dynamics. We found that the
      spatiotemporal behaviour of spiral waves strongly depends on the kinetics of
      betaAR activation. When betaAR activation is rapid, a stable spiral wave turns
      into small fragments and its electrocardiogram reveals the transition from VT to
      VF. This is due to the transiently steepened APD restitution induced by the
      faster activation of ICaL vs. IKs upon sudden betaAR activation. The spiral wave
      may also disappear if its transient wavelength is too large to be supported by
      the tissue size upon sudden strong betaAR activation that prolongs APD
      transiently. When betaAR activation is gradual, a stable spiral wave remains
      such, because of more limited increase in both APD and slope of APD restitution
      due to more contemporaneous ICaL and IKs activation. CONCLUSION: Changes in APD
      restitution during betaAR activation revealed a novel transient spiral wave
      dynamics; this spatiotemporal characteristic strongly depends on the protocol of
      isoproterenol application.

PMID- 24569901
TI  - Dependence of phase-2 reentry and repolarization dispersion on epicardial and
      transmural ionic heterogeneity: a simulation study.
AB  - AIMS: Phase-2 reentry (P2R) is a local arrhythmogenic phenomenon where
      electrotonic current propagates from a spike-and-dome action potential region to
      re-excite a loss-of-dome action potential region. While ionic heterogeneity has
      been shown to underlie P2R within the epicardium and has been hypothesized to
      occur transmurally, we are unaware of any study that has investigated the effects
      of combining these heterogeneities as they occur in the heart. Thus, we tested
      the hypothesis that P2R can result by either epicardial or transmural
      heterogeneity and that the realistic combination of the two would increase the
      likelihood of P2R. METHODS AND RESULTS: We used computational ionic models of
      cardiac myocyte dynamics to investigate initiation and development of P2R in
      simulated tissues with different ionic heterogeneities. In one-dimensional
      transmural cable simulations, P2R occurred when the conductance of the transient
      outward current in the epicardial region was near the range for which epicardial
      action potentials switched intermittently between spike-and-dome and loss-of-dome
      morphologies. Phase-2 reentry was more likely in two-dimensional tissue
      simulations by both epicardial and transmural heterogeneity and could expand
      beyond its local initiation site to create a macroscopic reentry. CONCLUSION: The
      characteristics and stability of action potential morphology in the epicardium
      are important determinants of the occurrence of both transmural and epicardial
      P2R and its associated arrhythmogenesis.

PMID- 24569904
TI  - Prevalence of gambling problems among the clients of a toronto homeless shelter.
AB  - Few studies have examined the prevalence of problem and pathological gambling
      among clients of homeless service agencies. The objective of this study was to
      estimate the prevalence of problem gambling among these clients. We collected
      primary data on gambling using the NORC diagnostic screen for disorders. Using a
      modified time-location recruitment approach 264 clients of a community homeless
      service agency were screened for lifetime gambling problems. Descriptive
      statistics were produced using SPSSX. The prevalence of lifetime problem gambling
      was 10 % and that of pathological gambling was 25 % in this sample. The
      prevalence of lifetime problem and pathological gambling was alarmingly high
      relative to the general population lifetime prevalence. Better insight into
      interventions for gambling that might reduce risk of homelessness will help
      service agencies gauge the needs of their clients and to implement change to
      service delivery and screening practices.

PMID- 24569903
TI  - Retrospective evaluation of canine and feline maxillomandibular trauma cases. A
      comparison of signalment with non-maxillomandibular traumatic injuries (2003
      2012).
AB  - OBJECTIVES: To determine differences in signalment between maxillomandibular (MM)
      and non-maxillomandibular (non-MM) trauma patients to help predict the type of
      injury sustained. METHODS: A medical records database was searched from December
      2003 to September 2012 to identify all MM trauma patients. A random sample of non
      MM trauma patients was generated for comparison. Patient species, age, sex,
      weight, and injury aetiology were recorded for both populations. RESULTS: Sixty
      seven MM trauma patients and 129 non-MM trauma patients were identified. Feline
      patients were almost twice as likely to be presented for MM trauma compared with
      non-MM trauma. The median weight of canine patients suffering MM injury was
      significantly less than that of non-MM patients (p = 0.025). A significant
      association existed between the causes of injuries associated with MM and non-MM
      trauma populations (p = 0.000023). The MM trauma patients were more likely to
      sustain injury as a result of an animal altercation (Bonferroni p = 0.001) while
      non-MM injuries were more likely to result from motor vehicle accidents
      (Bonferroni p = 0.001). Overall, animals that were less than one year of age with
      traumatic injuries were overrepresented (65/196) in comparison to the entire
      patient population. CLINICAL SIGNIFICANCE: The results of this study may help
      guide clinicians in the evaluation and screening of trauma patients that are
      presented as an emergency. Cats, small dogs and animals suffering from animal
      altercations should all be closely evaluated for MM injury.

PMID- 24569906
TI  - Comment on: "Recommendations to prescribe in complex older adults: results of the
      CRIteria to assess appropriate Medication use among Elderly complex patients
      (CRIME) project".

PMID- 24569907
TI  - Authors' reply to Bahat: "Recommendations to prescribe in complex older adults:
      results of the CRIteria to assess appropriate Medication use among Elderly
      complex patients (CRIME) project".

PMID- 24569909
TI  - Self-tuning GMV control of glucose concentration in fed-batch baker's yeast
      production.
AB  - A detailed system identification procedure and self-tuning generalized minimum
      variance (STGMV) control of glucose concentration during the aerobic fed-batch
      yeast growth were realized. In order to determine the best values of the
      forgetting factor (lambda), initial value of the covariance matrix (alpha), and
      order of the Auto-Regressive Moving Average with eXogenous (ARMAX) model (n a, n
      b), transient response data obtained from the real process wereutilized. Glucose
      flow rate was adjusted according to the STGMV control algorithm coded in Visual
      Basic in an online computer connected to the system. Conventional PID algorithm
      was also implemented for the control of the glucose concentration in aerobic fed
      batch yeast cultivation. Controller performances were examined by evaluating the
      integrals of squared errors (ISEs) at constant and random set point profiles.
      Also, batch cultivation was performed, and microorganism concentration at the end
      of the batch run was compared with the fed-batch cultivation case. From the
      system identification step, the best parameter estimation was accomplished with
      the values lambda = 0.9, alpha = 1,000 and n a = 3, n b = 2. Theoretical control
      studies show that the STGMV control system was successful at both constant and
      random glucose concentration set profiles. In addition, random effects given to
      the set point, STGMV control algorithm were performed successfully in
      experimental study.

PMID- 24569905
TI  - Non-renal effects and the risk assessment of environmental cadmium exposure.
AB  - BACKGROUND: Exposure to cadmium (Cd) has long been recognized as a health hazard,
      both in industry and in general populations with high exposure. Under the
      currently prevailing health risk assessment, the relationship between urinary Cd
      (U-Cd) concentrations and tubular proteinuria is used. However, doubts have
      recently been raised regarding the justification of basing the risk assessment on
      this relationship at very low exposure. OBJECTIVES: Our objective was to review
      available information on health effects of Cd exposure with respect to human
      health risk assessment. DISCUSSION: The associations between U-Cd and urinary
      proteins at very low exposure may not be due to Cd toxicity, and the clinical
      significance of slight proteinuria may also be limited. More importantly, other
      effects have been reported at very low Cd exposure. There is reason to challenge
      the basis of the existing health risk assessment for Cd. Our review of the
      literature found that exposure to low concentrations of Cd is associated with
      effects on bone, including increased risk of osteoporosis and fractures, and that
      this observation has implications for the health risk assessment of Cd. Other
      effects associated with Cd should also be considered, in particular cancer,
      although the information is still too limited for appropriate use in quantitative
      risk assessment. CONCLUSION: Non-renal effects should be considered critical
      effects in the health risk assessment of Cd.

PMID- 24569910
TI  - Utilization of makgeolli sludge filtrate (MSF) as low-cost substrate for
      bacterial cellulose production by Gluconacetobacter xylinus.
AB  - Search for efficient low-cost substrate/additives are gaining significant impetus
      in bacterial cellulose (BC) production. Makgeolli sludge (a traditional Korean
      wine distillery waste) is enriched with organic acid, alcohol, and sugar. Using
      makgeolli sludge filtrate (MSF) and Hestrin-Schramm (HS) medium (g/l of distilled
      water: glucose, 10.0; peptone, 5.0; yeast extract, 5.0; disodium phosphate, 2.7;
      citric acid, 1.15; pH 5.0), two different media-namely the modified HS media
      (ingredients of HS media except glucose dissolved in MSF) and mixed modified HS
      media (equal volume mixture of original and modified HS media)-were formulated.
      BC production with Gluconacetobacter xylinus was studied using the two above
      referred medium. Keeping HS medium as reference, effect of initial pH, glucose,
      ethanol, and organic acid concentration on BC production was also studied. It
      suggests that increasing initial glucose (up to 25 g/l) though improves BC
      production but results in poor BC yield above 15 g/l of glucose. However,
      addition of alcohol (up to 1%v/v) or citric acid (up to 20 mM) escalate
      productivity up to four and two times, respectively. In both modified HS media
      and mixed modified HS medium, BC production was four to five times higher than
      that of original HS medium. Even MSF alone surpassed HS medium in BC production.
      Scanning electron microscopy showed that BC microfibrils from MSF based media
      were several micrometers long and about 25-60 nm widths. X-ray diffraction
      patterns suggested the produced BC were of cellulose I polymorph.

PMID- 24569912
TI  - Prediction of treatment-related toxicity and outcome with geriatric assessment in
      elderly patients with solid malignancies treated with chemotherapy: a systematic
      review.
AB  - INTRODUCTION: The number of older patients with cancer is increasing. Standard
      clinical evaluation of these patients may not be sufficient to determine
      individual treatment strategies and therefore Geriatric Assessment (GA) may be of
      clinical value. In this review, we summarize current literature that is available
      on GA in elderly patients with solid malignancies who receive chemotherapy. We
      focus on prediction of treatment toxicity, mortality and the role of GA in the
      decision-making process. DESIGN: We conducted a systematic search in PubMed.
      Studied populations needed to fulfill the following criteria: 65 years or older,
      diagnosis of solid malignancy, treatment with chemotherapy, submission to GA,
      either designed to study prediction of treatment toxicity or mortality or to
      evaluate the role of GA in the decision-making process. RESULTS: Our search
      provided 411 publications. Thirteen met the predefined criteria. These studies
      revealed: (i) up to 64% of elderly patients suffer from severe toxicity caused by
      polychemotherapy, (ii) Nutritional status, functionality and comorbidity are
      often associated with worse outcome, (iii) GA reveals (unknown) geriatric
      problems in more than 50% of elderly patients with cancer and (iv) 21%-53% of
      chemotherapy regimens are being modified based on GA. CONCLUSIONS: In geriatric
      oncology, an accurate predictive test to guide anticancer treatment in order to
      prevent serious toxicity is needed. The value of GA in predicting toxicity and
      mortality in older patients with cancer undergoing treatment with chemotherapy
      has not been proven. It may be valuable in revealing geriatric problems but
      current evidence for its usefulness to guide treatment decisions in this setting
      is limited. However, we are convinced that GAs should be carried out to optimize
      treatment strategies in elderly patients with cancer to improve treatment
      efficacy and minimize toxicity.

PMID- 24569913
TI  - Early recognition of malnutrition and cachexia in the cancer patient: a position
      paper of a European School of Oncology Task Force.
AB  - BACKGROUND: Weight loss and cachexia are common, reduce tolerance of cancer
      treatment and the likelihood of response, and independently predict poor outcome.
      METHODS: A group of experts met under the auspices of the European School of
      Oncology to review the literature and-on the basis of the limited evidence at
      present-make recommendations for malnutrition and cachexia management and future
      research. CONCLUSIONS: Our focus should move from end-stage wasting to supporting
      patients' nutritional and functional state throughout the increasingly complex
      and prolonged course of anti-cancer treatment. When inadequate nutrient intake
      predominates (malnutrition), this can be managed by conventional nutritional
      support. In the presence of systemic inflammation/altered metabolism (cachexia),
      a multi-modal approach including novel therapeutic agents is required. For all
      patients, oncologists should consider three supportive care issues: ensuring
      sufficient energy and protein intake, maintaining physical activity to maintain
      muscle mass and (if present) reducing systemic inflammation. The results of phase
      II/III trials based on novel drug targets (e.g. cytokines, ghrelin receptor,
      androgen receptor, myostatin) are expected in the next 2 years. If effective
      therapies emerge, early detection of malnutrition and cachexia will be
      increasingly important in the hope that timely intervention can improve both
      patient-centered and oncology outcomes.

PMID- 24569911
TI  - Treatment developments and the unfolding of the quality of life discussion in
      childhood medulloblastoma: a review.
AB  - PURPOSE: To describe how the quality of life (QOL) discussion in childhood
      medulloblastoma (MB) relates to treatment developments, survival and sequelae
      from 1920 to 2014. METHODS: Articles containing "childhood medulloblastoma" and
      "quality of life" were identified in PubMed. Those containing phrases pertaining
      to psychological, emotional, behavioral or social adjustment in the title,
      abstract or keywords were selected. Inclusion of relevant older publications was
      assured by cross-checking references. RESULTS: 1920-1930s: suction, electro
      surgery, kilovolt (KV) irradiation. Survival = months. Focus on operative
      mortality, symptoms and survival. 1940s: radiotherapy improved. 1950s:
      chemotherapy and intubation. Survival = years. Opinions oscillated between
      optimism/awareness of physical sequelae of radiotherapy. 1960s: magnified vision,
      ventriculo-peritoneal (VP) shunts, megavolt (MV) irradiation. Long-term survival
      shifted the attention towards neurological problems, disability and
      carcinogenesis of radiotherapy. 1970s: CT, microscope, bipolar coagulation, shunt
      filters, neuroanesthesia, chemotherapy trials and staging studies. Operative
      mortality decreased and many patients (re)entered school; emphasis on
      neuropsychological sequelae, IQ and academic performance. 1980s: magnetic
      resonance imaging (MRI), Cavitron ultrasonic aspiration (CUSA), laser surgery,
      hyper-fractionated radiotherapy (HFRT). Cerebellar mutism, psychological and
      social issues. 1990s: pediatric neurosurgery, proton beams, stem cell rescue.
      Reflections on QOL as such. 21st century: molecular genetics. Premature aging,
      patterns of decline, risk- and resilience factors. DISCUSSION: QOL is a critical
      outcome measure. Focus depends on survival and sequelae, determined after years
      of follow-up. Detailed measurements are limited by time, money and human
      resources, and self-reporting questionnaires represent a crude measure limited by
      subjectivity. Therapeutic improvements raise the question of QOL versus cure. QOL
      is a potential primary research endpoint; multicenter international studies are
      needed, as are web-based tools that work across cultures.

PMID- 24569915
TI  - Deciphering root causes of intrinsic BRAF inhibitor resistance in melanoma:
      ushering in a new genomics case reports feature for Annals of Oncology.

PMID- 24569914
TI  - Phase III placebo-controlled double-blind randomized trial of radiotherapy for
      stage IIB-IVA cervical cancer with or without immunomodulator Z-100: a JGOG
      study.
AB  - BACKGROUND: Based on the result of our previous study showing better overall
      survival (OS) at the lower dose (0.2 ug) of immunomodulator Z-100 than higher
      dose (40 ug) in patients with locally advanced cervical cancer who received
      radiotherapy, we conducted a placebo-controlled double-blind randomized trial.
      PATIENTS AND METHODS: Patients of stages IIB-IVA squamous cell carcinoma of the
      uterine cervix were randomly assigned to receive Z-100 at 0.2 ug (Z) or placebo
      (P). The study agent was given subcutaneously twice a week during the
      radiotherapy, followed by maintenance therapy by administering once every 2 weeks
      until disease progression. Primary end point was OS, and secondary end points
      were recurrence-free survival, and toxicity. RESULTS: A total of 249 patients
      were randomized. Death events occurred extremely slower than expected, and
      Independent Data Monitoring Committee recommended to analyze the survival result
      prematurely. The 5-year OS rate was 75.7% [95% confidence interval (CI) 66.4% to
      82.8%] for Arm Z and 65.8% (95% CI 56.2% to 73.8%) for Arm P (P = 0.07); hazard
      ratio was 0.65 (95% CI 0.40-1.04). Survival benefit in Arm Z was observed
      regardless of chemoradiation or radiation alone. There was no trend in recurrence
      free survival between the two arms. Side-effects were not different between two
      arms. CONCLUSION: Z-100 showed a trend of improvement on OS in locally advanced
      cervical cancer, although the statistical power was less than anticipated because
      survival rates were unexpectedly higher than expected for both arms. Validation
      of potential survival benefit of immune modulation should be made. TRIAL
      REGISTRATION: umin.ac.jp/ctr Identifier: C000000221.

PMID- 24569916
TI  - Adjuvant chemotherapy for bladder cancer-why does level 1 evidence not support
      it?
AB  - Neoadjuvant cisplatin-based combination chemotherapy provides a 5% increase in
      cure rate, an increase in median survival of about 3 years, and statistically
      significant and clinically relevant increments in overall survival for patients
      with invasive bladder cancer. Despite compelling level 1 data, it has become
      quite clear that facts that are similar to those that changed the paradigm of
      treatment of breast cancer in the 1970s have not had a similar influence on
      patterns of practice in bladder cancer care. Instead of using this proven
      approach, cystectomy alone or surgery followed by adjuvant chemotherapy is often
      used as a functional alternative for patients with deeply invasive and/or node
      metastatic disease discovered at radical cystectomy. However, there is no well
      powered level 1 evidence to support routine adjuvant chemotherapy for invasive
      bladder cancer, and some randomized trials have shown inferior outcomes. There is
      a clear need for a well-designed, randomized trial that tests the utility of
      adjuvant chemotherapy for invasive bladder cancer, but until that has been
      completed, neoadjuvant chemotherapy followed by definitive local treatment should
      be the standard of care for invasive bladder cancer. 

PMID- 24569917
TI  - Demystifying the role of tumor HPV status in recurrent and/or metastatic squamous
      cell carcinoma of the head and neck.

PMID- 24569918
TI  - Design, synthesis and properties of artificial nucleic acids from (R)-4-amino
      butane-1,3-diol.
AB  - A new artificial nucleic acid analogue, (R)-Am-BuNA, was developed with a
      simplified acyclic (R)-4-amino-butane-1,3-diol phosphodiester backbone.
      Phosphoramidite monomers of (R)-Am-BuNA were incorporated into DNA
      oligonucleotides (ODNs) and G-quadruplexes. Their thermal stability, conformation
      change and biological stability were further investigated using UV-melting,
      circular dichroism (CD) and gel electrophoresis. The results suggested that
      thermal stability of the duplexes of (R)-Am-BuNA modified ODNs and their
      complementary ODN is highly dependent on the substitution position. Substitution
      of thymidine at the 7th position in a thrombin-binding DNA aptamer (TBA) results
      in a slight increase in Tm with no effect on quadruplex conformation on the CD
      spectrum in comparison to that of the natural G-quadruplex. Further enzymatic
      experiments with fetal bovine serum (FBS) and snake venom phosphodiesterase
      (SVPDE) indicated that only single replacement of a (R)-Am-BuNA modified
      nucleobase greatly inhibited oligonucleotide degradation, which shows their
      promising applications as capping nucleotides in nucleic acid drugs. 

PMID- 24569919
TI  - Site-specific thigh muscle loss as an independent phenomenon for age-related
      muscle loss in middle-aged and older men and women.
AB  - The purpose of this study was to examine the relationships between dual-energy X
      ray absorptiometry (DXA)-determined appendicular lean mass (aLM) and ultrasound
      measured thigh muscle thickness (MTH) ratio and between aLM or thigh MTH ratio
      and zigzag walking performance. Eighty-one middle-aged and older adults (41 men
      and 40 women) aged 50 to 74 years volunteered for the study. Approximately two
      thirds of the subjects (34 men and 17 women) carried out regular sports activity
      (at least >2 times a week) including running and cycling exercise. MTH was
      measured using B-mode ultrasound at two sites on the anterior (A50) and posterior
      (P50) aspects of the mid-thigh. A50:P50 MTH ratio was calculated to evaluate site
      specific thigh muscle loss. aLM and percent body fat were also determined using a
      DXA. Men had lower body fat and higher aLM than women. Anterior and posterior
      thigh MTH as well as A50:P50 MTH ratio was higher in men than in women. Zigzag
      walking time was faster in men than in women. Anterior and posterior thigh MTH
      was positively (p < 0.001) correlated to aLM and aLM index in men and women.
      However, A50:P50 MTH ratio was not significantly correlated with aLM and aLM
      index in both sexes. There was no significant correlation between aLM index and
      zigzag walking time in men and women. A50:P50 MTH ratio was inversely (p < 0.05)
      correlated to zigzag walking time in both men and women. Our results suggest that
      thigh MTH ratio is independent of age-related muscle mass loss detected by aLM.

PMID- 24569920
TI  - Getting from choosing wisely to spending wisely.

PMID- 24569921
TI  - A man with urethral polyembolokoilamania successfully treated with
      electroconvulsive therapy.
AB  - Polyembolokoilamania is the act of inserting foreign objects into bodily orifices
      and can be classified as a paraphilia if done for sexual pleasure. Although
      problematic sexual behaviors are common in dementia, the majority of case reports
      of urethral polyembolokoilamania in the elderly have occurred in the absence of
      dementia or cognitive impairment. Little empirical evidence exists for managing
      problematic sexual behaviors in the elderly and in dementia. Most evidence in the
      form of case reports demonstrates that behavioral, environmental, and
      pharmacological interventions can be effective. In this case report, we describe
      the management of sexually disinhibited behavior in the form of
      polyembolokoilamania in a 67-year-old man suffering from treatment-resistant
      depression, obsessive compulsive disorder, and early signs of frontotemporal
      dementia. The successful treatment included a course of electroconvulsive
      therapy. 

PMID- 24569922
TI  - Experimental and analytical investigation of the thermal necrosis in high-speed
      drilling of bone.
AB  - Bone loss due to thermo necrosis may weaken the purchase of surgically placed
      screws and pins, causing them to loosen postoperatively. The heat generated
      during the bone drilling is proportional to cutting speed and force and may be
      partially dissipated by the blood and tissue fluids, and somehow carried away by
      the chips formed. Increasing cutting speed will reduce cutting force and
      machining time. Therefore, it is of interest to study the effects of the
      increasing cutting speed on bone drilling characteristics. In this article, the
      effects of the increasing cutting speed ranging from 500 up to 18,000 r/min on
      the thrust force and the temperature rise are studied for bovine femur bone. The
      results of this study reveal that the high-speed drilling of 6000-7000 r/min may
      effectively reduce the two parameters of maximum cortical temperature and
      duration of exposure at temperatures above the allowable levels, which in turn
      reduce the probability of thermal necrosis in the drill site. This is due to the
      reduction of the cutting force and the increase in the chip disposal speed.
      However, more increases in the drill bit rotational speed result in an increase
      in the amount of temperature elevation, not because of sensible change in
      drilling force but a considerable increase in friction among the chips, drill bit
      and the hole walls.

PMID- 24569923
TI  - Absent trochlear nerve with transient diplopia.

PMID- 24569924
TI  - Results from a pilot study on amiodarone administration in monogenic
      frontotemporal dementia with granulin mutation.
AB  - Frontotemporal dementia (FTD) is one of the most important neurodegenerative
      conditions and Granulin (GRN) is one of the major genes associated to the
      disease. FTD-GRN patients are still orphan for any evidence-based target-therapy
      approach. Interestingly, it has been recently found that alkalizing agents
      rescued haploinsufficiency in cellular models expressing FTD-GRN mutations. We
      set up a pilot phase II clinical trial in five FTD patients with GRN
      Thr272s(g.1977_1980delCACT) mutation, to determine if amiodarone (200 mg/day) may
      (1) reverse progranulin deficiency and (2) delay disease progression. Each
      patient was scheduled for 7 study visits over 12 months period. We assessed GRN
      levels at baseline and after amiodarone administration during the treatment
      course. Somatic and neurologic examinations, along with cognitive and behavioral
      assessment were recorded as well. No significant effect on peripheral GRN levels
      was observed. In treated FTD, disease course did not differ when compared with a
      group of untreated FTD-GRN patients. This is the first trial targeting
      progranulin rescue in FTD-GRN patients using amiodarone. Despite the negative
      findings, it may be interesting to extend this attempt to a larger sample of
      subjects and to other alkalizing agents to restore granulin haploinsufficiency.

PMID- 24569926
TI  - Reactions of enantiopure cyclic diols with sulfuryl chloride.
AB  - Monocyclic allylic cis-1,2-diols reacted with sulfuryl chloride at 0  degrees C
      in a regio- and stereo-selective manner to give 2-chloro-1-sulfochloridates,
      which were hydrolysed to yield the corresponding trans-1,2-chlorohydrins. At -78 
      degrees C, with very slow addition of sulfuryl chloride, cyclic sulfates were
      formed in good yields, proved to be very reactive with nucleophiles and rapidly
      decomposed on attempted storage. Reaction of a cyclic sulfate with sodium azide
      yielded a trans-azidohydrin without evidence of allylic rearrangement occurring.
      An enantiopure bicyclic cis-1,2-diol reacted with sulfuryl chloride to give,
      exclusively, a trans-1,2-dichloride enantiomer with retention of configuration at
      the benzylic centre and inversion at the non-benzylic centre; a mechanism is
      presented to rationalise the observation.

PMID- 24569925
TI  - Retrospective evaluation of canine and feline maxillomandibular trauma cases.
      Comparison of lunar cycle and seasonality with non-maxillomandibular traumatic
      injuries (2003-2012).
AB  - OBJECTIVES: To determine relationships between seasonality and lunar cycle and
      the frequency of maxillomandibular (MM) and non-maxillomandibular (non-MM) injury
      in canine and feline trauma patients. METHODS: A medical records database was
      searched to identify all MM trauma patients (n = 67) and a random sample of non
      MM trauma patients (n = 129) according to search criteria. Season of injury, moon
      phase, and moon luminosity were calculated for the date of injury. RESULTS:
      Maxillomandibular injury occurred predominately in the spring and decreased
      through winter while non-MM injury occurred more frequently in the summer and
      fall. The difference in the frequency of MM and non-MM injuries during different
      seasons was not significant (p = 0.071). When comparing the amount of moon
      illuminated when injuries occurred during the quarters before or after the full
      moon, a difference (p = 0.007) was noted with a greater number of injuries
      occurring immediately following the full moon. CLINICAL SIGNIFICANCE: These
      results may guide clinicians to closely evaluate trauma patients that are
      presented on emergency during a particular season or lunar phase. Based on the
      season at the time of injury, close evaluation for MM versus non-MM trauma may be
      appropriate.

PMID- 24569927
TI  - The application of Hippocratic principles to pediatric radiology.

PMID- 24569928
TI  - OK-432 sclerotherapy of lymphatic malformation in the head and neck: factors
      related to outcome.
AB  - BACKGROUND: No previous study to the best of our knowledge has examined the
      multiple factors related to the outcome of OK-432 sclerotherapy of lymphatic
      malformations. OBJECTIVE: This study aimed to assess factors related to the
      successful outcome of OK-432 sclerotherapy for lymphatic malformations in the
      head and neck region. MATERIALS AND METHODS: During a 6-year period, OK-432
      sclerotherapy was performed in 26 patients with lymphatic malformations. Several
      factors related to the efficacy of OK-432 sclerotherapy were evaluated, including
      the type (macrocystic or microcystic), the maximum lesion diameter, amount and
      hemorrhagic cytology of the aspirate, degree of aspiration, injected dose of OK
      432 and post-therapy inflammation-related symptom. In all cases, ultrasound (US)
      follow-up was performed. RESULTS: Of the 26 cases, 13 (50%) showed successful
      elimination of the lymphatic malformations in the follow-up US after the initial
      session, and all successful cases were of the macrocystic type. The type of
      lymphatic malformation and the success of OK-432 sclerotherapy were significantly
      related (P = 0.0149). Of the 16 cases of complete aspiration, 11 (68.8%) showed a
      successful outcome. Further, of the 17 cases with inflammation-related symptom,
      13 (76.5%) showed a successful outcome. While the degree of aspiration and
      presence of inflammation-related symptom showed a significant relationship with
      the success of OK-432 sclerotherapy (P < 0.05), no other factors showed a
      significant relationship. CONCLUSION: The study results suggest that the
      macrocystic type and complete aspiration of cystic contents were important
      factors for the success of OK-432 sclerotherapy of lymphatic malformations, and
      that inflammation-related symptom was a predictor of a successful outcome.

PMID- 24569929
TI  - The role and mechanism of exogenous calcitonin gene-related peptide on
      mesenchymal stem cell proliferation and osteogenetic formation.
AB  - The aims of this study were to expose the function of calcitonin gene-related
      peptide (CGRP) in the proliferation and intracellular communication of
      mesenchymal stem cells (MSCs), to observe the change in IGF-1, BMP-2 and their
      receptor in the MSCs cell with exogenous CGRP, and to explore whether exogenous
      CGRP will induce MSCs to express the osteoinduced factor and it's receptor. MSCs
      were separated from bone marrow and collected by gradient centrifugation and
      adherent culture. Real-time polymerase chain reaction (RT-PCR) was used to detect
      CGRP receptor in MSCs in logarithmic growth phase [1]. Hybridoma technique was
      used to produce rabbit-anti-human CGRP receptor, which was used in the Western
      blot test to detect CGRP receptor protein produced in human MSCs. Then, MSCs were
      parted into 3 groups decided by the concentration of CGRP. Cell proliferation was
      detected through methylthiazol tetrazolium (MTT) test. Cell form in each group
      was detected through optical microscope, in the same time point. Cell cycle was
      detected with flow cytometric to analyze the ratio of cell in the mitotic time.
      MSCs collected from healthy volunteer were parted into 3 groups: the control
      group, the anagen group, and the experimental group. Intracellular communication
      medium molecule was detected through radioimmunoassay; intracellular
      communication and signal conduction were detected through carboxyfluorescein
      diacetate fluorescent dye. The expression of Cx43mRNA was detected through real
      time PCR. The mRNA expressions of proliferation-related biological factor of MSCs
      were detected through real-time PCR. MSCs collected by gradient centrifugation
      and cultured by adherent culture have high purity and proliferation effect. It
      was proved through RT-PCR that MSCs express CGRP receptor mRNA, and it was also
      be proved through Western blot that MSCs express CGRP receptor protein. The MTT
      test showed similar result, the 10-8 mol/L CGRP group had the highest
      proliferation speed, and the control group had the lowest. There is statistical
      difference between experimental group and control group. There also had static
      difference between the 10-8 mol/L CGRP group and the other two experimental
      group. Expression of Cx43mRNA in experimental group was higher than the other two
      groups, but, without static difference. It was proved that the mRNA expressions
      of IGF-1, IGF-1 receptor, and BMP-2 receptor in experimental group were higher
      than that in control group with static difference. The mRNA expressions of BMP-2
      in all the groups had no static difference. And Ct index in all the groups were
      higher than 35. It was proved that MSCs express CGRP receptor mRNA and protein.
      With MTT test, it had been proved that exogenous CGRP can accelerate the
      proliferation speed in the logarithmic growth phase. With flow cytometric, it had
      been proved that exogenous CGRP can raise the ratio of the cell in the DNA
      synthesis period and mitosis prophase. CGRP can promote not only intracellular
      communication of MSCs but also the expression of Cx43mRNA. The exogenous CGRP can
      increase the mRNA expression of IGF-1, IGF-1 receptor, and BMP-2 receptor of
      MSCs. In all the groups, the Ct indexes of BMP-2mRNA were higher than 35, which
      could be considered as negative expression.

PMID- 24569930
TI  - Inhibition of hepatitis B virus cccDNA by siRNA in transgenic mice.
AB  - The elimination of viral covalently closed circular DNA (cccDNA) from the nucleus
      of infected hepatocytes is an obstacle to achieving sustained viral clearance
      during antiviral therapy of chronic hepatitis B virus (HBV) infection. The aim of
      our study was to determine whether treatment with siRNA is able to suppress viral
      cccDNA amplification using a HBV-transgenic mice model. The experimental results
      revealed that siRNAs can serve as efficient alternative anti-HBV agents, because
      they showed better inhibitory effect on viral replication and antigen expression
      in transgenic mice. More importantly, the siRNA markedly inhibited HBV cccDNA
      amplification. 

PMID- 24569932
TI  - [Augmented spontaneous breathing in the weaning process: technical gimmick or
      enrichment of intensive care medicine?].

PMID- 24569933
TI  - [Parental presence during induction of anesthesia in children: pros and cons].
AB  - There is a high level of evidence that parental presence during induction of
      anesthesia in children does not lead to a reduction of fear and better
      cooperation of the child. However, pediatric anesthetists often encounter the
      request of parents to be present during the induction of anesthesia which is
      current practice in many countries. This article explains the grounds and the
      premises for this practice and describes those factors which might be important
      to support parental presence during induction of anesthesia in children. Some
      practical advice and tips on how parental presence in the clinic can be
      practically implemented are given at the end of the article. 

PMID- 24569931
TI  - [Mechanical resuscitation assist devices].
AB  - In Germany 100,000-160,000 people suffer from out-of-hospital cardiac arrest
      (OHCA) annually. The incidence of cardiopulmonary resuscitation (CPR) after OHCA
      varies between emergency ambulance services but is in the range of 30-90 CPR
      attempts per 100,000 inhabitants per year. Basic life support (BLS) involving
      chest compressions and ventilation is the key measure of resuscitation. Rapid
      initiation and quality of BLS are the most critical factors for CPR success. Even
      healthcare professionals are not always able to ensure the quality of CPR
      measures. Consequently in recent years mechanical resuscitation devices have been
      developed to optimize chest compression and the resulting circulation. In this
      article the mechanical resuscitation devices currently available in Germany are
      discussed and evaluated scientifically in context with available literature. The
      ANIMAX CPR device should not be used outside controlled trials as no clinical
      results have so far been published. The same applies to the new device Corpuls
      CPR which will be available on the market in early 2014. Based on the current
      published data a general recommendation for the routine use of LUCASTM and
      AutoPulse(r) CPR cannot be given. The preliminary data of the CIRC trial and the
      published data of the LINC trial revealed that mechanical CPR is apparently
      equivalent to good manual CPR. For the final assessment further publications of
      large randomized studies must be analyzed (e.g. the CIRC and PaRAMeDIC trials).
      However, case control studies, case series and small studies have already shown
      that in special situations and in some cases patients will benefit from the
      automatic mechanical resuscitation devices (LUCASTM, AutoPulse(r)). This applies
      especially to emergency services where standard CPR quality is far below average
      and for patients who require prolonged CPR under difficult circumstances. This
      might be true in cases of resuscitation due to hypothermia, intoxication and
      pulmonary embolism as well as for patients requiring transport or coronary
      intervention when cardiac arrest persists. Three prospective randomized studies
      and the resulting meta-analysis are available for active compression
      decompression resuscitation (ACD-CPR) in combination with an impedance threshold
      device (ITD). These studies compared ACD-ITD-CPR to standard CPR and clearly
      demonstrated that ACD-ITD-CPR is superior to standard CPR concerning short and
      long-term survival with good neurological recovery after OHCA. 

PMID- 24569934
TI  - [Overwhelming postsplenectomy infection syndrome].
AB  - The overwhelming postsplenectomy infection syndrome (OPSI) is a fulminant sepsis
      that is mainly caused by Streptococcus pneumoniae and is characterized by a
      particular high mortality. Patients whose spleen was removed due to a
      hematological disease are at special risk. Even after the recommended
      immunization against Streptococcus pneumoniae 20-30 % of these patients do not
      develop an adequate level of antibody response. Therefore, this particular group
      of patients must be trained how to behave in case of fever and need to obtain
      immediate specific sepsis therapy with antibiotic prophylaxis. 

PMID- 24569935
TI  - [Prehospital non-invasive ventilation in Germany: results of a nationwide survey
      of ground-based emergency medical services].
AB  - BACKGROUND AND OBJECTIVES: Non-invasive ventilation (NIV) is an evidence-based
      treatment of acute respiratory failure and can be helpful to reduce morbidity and
      mortality. In Germany national S3 guidelines for inhospital use of NIV based on a
      large number of clinical trials were published in 2008; however, only limited
      data for prehospital non-invasive ventilation (pNIV) and hence no recommendations
      for prehospital use exist so far. AIM: In order to create a database for pNIV in
      Germany a nationwide survey was conducted to explore the status quo for the years
      2005-2008 and to survey expected future developments including disposability,
      acceptance and frequency of pNIV. MATERIAL AND METHODS: A questionnaire on the
      use of pNIV was developed and distributed to 270 heads of medical emergency
      services in Germany. RESULTS: Of the 270 questionnaires distributed 142 could be
      evaluated (52 %). The pNIV was rated as a reasonable treatment option in 91 % of
      the respondents but was available in only 54 out of the 142 responding emergency
      medical services (38 %). Continuous positive airway pressure (98 %) and biphasic
      positive airway pressure (22 %) were the predominantly used ventilation modes.
      Indications for pNIV use were acute cardiogenic pulmonary edema (96 %), acute
      exacerbation of chronic obstructive pulmonary disease (89 %), asthma (32 %) and
      pneumonia (28 %). Adverse events were reported for panic (20 +/-  17%) and non
      threatening heart rhythm disorders (8 +/- 5%), the rate of secondary intubation
      was low (reduction from 20 % to 10 %) and comparable to data from inhospital
      treatment. CONCLUSION: Prehospital NIV in Germany was used by only one third of
      all respondents by the end of 2008. Based on the clinical data a growing
      application for pNIV is expected. Controlled prehospital studies are needed to
      enunciate evidence-based recommendations for pNIV.

PMID- 24569936
TI  - Prevalence of oral malodour and its relationship with oral parameters in Indian
      children aged 7-15 years.
AB  - AIM: To determine the prevalence of oral malodour in Indian children and also to
      assess the relationship of oral malodour with oral hygiene, gingival health,
      dental caries, tongue coating, mouth breathing and frequency of tooth brushing.
      METHOD: A total number of 900 school children (7-15 years) were included in the
      study. Children were assessed for the oral malodour, oral hygiene, gingival
      health, dental caries, tongue coating, mouth breathing and frequency of tooth
      brushing. RESULTS: The prevalence of oral malodour in Davangere school children
      was found to be 40.9%. Oral malodour was significantly (p < 0.001) associated
      with age, mouth breathing, tongue coating, oral hygiene status, gingival status
      and tooth brushing frequency. Oral malodour was not significantly correlated with
      gender and caries status. CONCLUSIONS: The prevalence of malodour in the
      population studied was 40.9% and oral health status and oral malodour were
      associated with one another. The prevalence of oral malodour was considerably
      high and should not be neglected in children.

PMID- 24569938
TI  - Knowledge, management and perceived barriers to treatment of molar-incisor
      hypomineralisation in general dental practitioners and dental nurses in Malaysia.
AB  - BACKGROUND: Molar-incisor hypomineralisation (MIH) is a global dental problem,
      yet little is known about the knowledge of the general dental practitioners
      (GDPs) and dental nurses (DNs) regarding this defect in South East Asia. AIMS: To
      assess and compare the knowledge of the GDPs and DNs in Malaysia regarding the
      frequency of occurrence of MIH within their practice, its diagnosis, putative
      aetiological factors and management. STUDY DESIGN AND METHODS: A questionnaire
      was distributed to GDPs and DNs during a nationwide dental conference in Melaka,
      Malaysia and who were asked to answer questions about demographic variables,
      knowledge, attitudes and practices in the management of MIH. STATISTICS:
      Descriptive statistics and bivariate analysis were performed. A 5% level of
      statistical significance was applied for the analyses. RESULTS: A response rate
      of 58.2% (131/225) was obtained. Most respondents were aware of MIH and
      encountered it in their practice (GDPs = 82.5%, DNs = 82.4%). The condition was
      observed by respondents less in primary molars compared to first permanent
      molars. Full agreement between GDPs and DNs did not exist concerning the
      aetiological factors and management of MIH. Glass ionomer cements were the most
      popular material used in treating MIH. Most respondents (GDPs = 93%, DNs = 76.5%)
      indicated that they had not received sufficient information about MIH and were
      willing to have clinical training in the diagnosis and therapeutic modalities of
      MIH. CONCLUSIONS: MIH is identified and encountered by most respondents.
      Agreement did not exist between GDPs and DNs concerning MIH frequency of
      occurrence within their practice, its diagnosis, aetiological factors and
      management.

PMID- 24569939
TI  - Crystal structure of the eukaryotic translation initiation factor 2A from
      Schizosaccharomyces pombe.
AB  - The eukaryotic translation initiation factor 2A (eIF2A) was identified as a
      factor that stimulates the binding of methionylated initiator tRNA (Met-tRNA i
      (Met) ) to the 40S ribosomal subunit, but its physiological role remains poorly
      defined. Recently, eIF2A was shown to be involved in unconventional translation
      initiation from CUG codons and in viral protein synthesis under stress conditions
      where eIF2 is inactivated. We determined the crystal structure of the WD-repeat
      domain of Schizosaccharomyces pombe eIF2A at 2.5 A resolution. The structure
      adopts a novel nine-bladed beta-propeller fold. In contrast to the usual beta
      propeller proteins, the central channel of the molecule has the narrower opening
      on the bottom of the protein and the wider opening on the top. Highly conserved
      residues are concentrated in the positively-charged top face, suggesting the
      importance of this face for interactions with nucleic acids or other initiation
      factors. 

PMID- 24569937
TI  - Related factors of dental caries and molar incisor hypomineralisation in a group
      of children with cystic fibrosis.
AB  - AIM: To investigate dental caries and molar incisor hypomineralisation (MIH)
      related factors such as treatment, diet, brushing and salivary factors in
      children with cystic fibrosis (CF) compared with healthy peers. STUDY DESIGN: A
      cohort study was performed. METHODS: This study was performed on 30 CF children
      comprising patients at the Faculty of Medicine and 30 control children recruited
      from the Dental School. Salivary factors, dental caries, MIH, daily diet,
      brushing habits were analysed. Statistical analysis was calculated by SPSS for
      Windows. RESULTS: Decay missing filled teeth (DMF-T) score was 4.6 +/- 4.0 in CF
      and 7.7 +/- 2.7 in control (p = 0.001). 43% of CF children with MIH were found to
      use antibiotics, but no significant difference in the caries experience was found
      with antibiotic usage (p > 0.05). DMF-T of CF adolescents (23%) who use
      Tobramycin was 7 +/- 3.5. DMF-T of CF children (20%) who take other antibiotics
      was 2.5 +/- 3.5, but no statistical difference was found (p = 0.054). Saliva pH,
      salivary flow rate, and buffering capacity were not found statistically
      significant (p > 0.05). STATISTICS: Percentage arithmetic mean value, standard
      deviation, independent sample t test, Fisher's exact test, Chi-square test and
      Mann-Whitney U test were used, while a p value of <0.05 was considered
      statistically significant. CONCLUSIONS: Medication and diet could be considered
      as a risk factor for dental caries and factors such as salivary pH, good oral
      hygiene could play a protective role for oral health CF children. MIH frequency
      and lower caries experience seen in CF children could be due to salivary factors
      or pharmacological treatment they take. The multidisciplinary approach team would
      be advantageous in the management of children with CF and oral health should be
      under control during early years of life by paediatric dentists.

PMID- 24569940
TI  - Establishment and characterization of a lung cancer cell line, SMC-L001, from a
      lung adenocarcinoma.
AB  - Lung cancer cell lines are a valuable tool for elucidating lung tumorigenesis and
      developing novel therapies. However, the majority of cell lines currently
      available were established from tumors in patients of Caucasian origin, limiting
      our ability to investigate how cancers in patients of different ethnicities
      differ from one another in terms of tumor biology and drug responses. In this
      study, we established a human non-small cell lung carcinoma cell line, SMC-L001,
      and characterized its genome and tumorigenic potential. SMC-L001 cells were
      isolated from a Korean lung adenocarcinoma patient (male, pStage IIb) and were
      propagated in culture. SMC-L001 cells were adherent. DNA fingerprinting analysis
      indicated that the SMC-L001 cell line originated from parental tumor tissue.
      Comparison of the genomic profile of the SMC-L001 cell line and the original
      tumor revealed an identical profile with 739 mutations in 46 cancer-related
      genes, including mutations in TP53 and KRAS. Furthermore, SMC-L001 cells were
      highly tumorigenic, as evidenced by the induction of solid tumors in
      immunodeficient mice. In summary, we established a new lung cancer cell line with
      point mutations in TP53 and KRAS from a Korean lung adenocarcinoma patient that
      will be useful for investigating ethnic differences in lung cancer biology and
      drug response. 

PMID- 24569941
TI  - Cellular mechanism of the nonmonotonic dose response of bisphenol A in rat
      cardiac myocytes.
AB  - BACKGROUND: The need for mechanistic understanding of nonmonotonic dose responses
      has been identified as one of the major data gaps in the study of bisphenol A
      (BPA). Previously we reported that acute exposure to BPA promotes
      arrhythmogenesis in female hearts through alteration of myocyte Ca(2+) handling,
      and that the dose response of BPA was inverted U-shaped. OBJECTIVE: We sought to
      define the cellular mechanism underlying the nonmonotonic dose response of BPA in
      the heart. METHODS: We examined rapid effects of BPA in female rat ventricular
      myocytes using video-edge detection, confocal and conventional fluorescence
      imaging, and patch clamp. RESULTS: The rapid effects of BPA in cardiac myocytes,
      as measured by multiple end points, including development of arrhythmic
      activities, myocyte mechanics, and Ca(2+) transient, were characterized by
      nonmonotonic dose responses. Interestingly, the effects of BPA on individual
      processes of myocyte Ca(2+) handling were monotonic. Over the concentration range
      of 10(-12) to 10(-6) M, BPA progressively increased sarcoplasmic reticulum (SR)
      Ca(2+) release and Ca(2+) reuptake and inhibited the L-type Ca(2+) current
      (I(CaL)). These effects on myocyte Ca(2+) handling were mediated by estrogen
      receptor (ER) beta signaling. The nonmonotonic dose responses of BPA can be
      accounted for by the combined effects of progressively increased SR Ca(2+)
      reuptake/release and decreased Ca(2+) influx through I(CaL). CONCLUSION: The
      rapid effects of BPA on female rat cardiac myocytes are characterized by
      nonmonotonic dose responses as measured by multiple end points. The nonmonotonic
      dose response was produced by ERbeta-mediated monotonic effects on multiple
      cellular Ca(2+) handling processes. This represents a distinct mechanism
      underlying the nonmonotonicity of BPA's actions.

PMID- 24569942
TI  - Roles of spatial partitioning, competition, and predation in the North American
      invasion of an exotic mosquito.
AB  - Invasion success and species coexistence are often mediated by species
      interactions across patchily distributed habitats and resources. The invasive
      mosquito Aedes japonicus japonicus has established in the North American range of
      the competitively superior resident congener, Aedes albopictus, and the predatory
      native mosquito Toxorhynchites rutilus. We tested predictions for two hypotheses
      of invasion success and species coexistence: keystone predation and spatial
      partitioning. We tested competition between A. japonicus japonicus and A.
      albopictus with or without T. rutilus in laboratory microcosms, and measured
      abundances of A. japonicus japonicus, A. albopictus, other resident competing
      mosquito species, and the presence of T. rutilus among tree holes and tires in
      metropolitan Washington, DC. In laboratory microcosms, A. albopictus was
      competitively dominant over A. japonicus japonicus, which is consistent with the
      few prior studies of competition between these two Aedes species. T. rutilus
      predation severely lowered performances of both Aedes species but more severely
      lowered A. japonicus japonicus performance than A. albopictus performance when
      all three species co-occurred, thus yielding no evidence for keystone predation.
      Consistent with the spatial partitioning hypothesis, A. japonicus japonicus was
      negatively correlated and independently aggregated with A. albopictus and all
      combined resident mosquito competitors and was not associated with T. rutilus
      among field containers. These results suggest that predation from T. rutilus and
      competition from A. albopictus are barriers to the spread of A. japonicus
      japonicus, but that A. japonicus japonicus may escape these interspecific effects
      by utilizing spatially partitioned container habitats. 

PMID- 24569944
TI  - Meta-analysis of the effects of exercise intervention on quality of life in
      breast cancer survivors.
AB  - Breast cancer is the most common type of cancer among women worldwide. Diagnosis
      and treatment of breast cancer pose an array of physical and psychological
      threats to the survivors. Exercise interventions may be particularly appropriate
      for cancer survivors because they have the potential to improve physical and
      psychological functioning. The review aims to examine the effectiveness of
      exercise intervention on the quality of life (QOL) of breast cancer survivors.
      Five databases (Medline, CINAHL, Scopus, The Cochrane Library, and CAJ Full-text
      Database) were searched from 2003 to July 2013. Clinical controlled trials of
      exercise interventions for breast cancer survivors who were at least 18 years old
      and had completed active cancer treatment were included. A total of 25 trials
      were included in this study, of which 19 were pooled together statistically.
      Subjects in the exercise interventions had higher overall QOL than subjects in
      the control group. The standardized mean difference (SMD) for changes in overall
      general QOL scores was 0.70 (95 % CI 0.21, 1.19). The SMD for changes in cancer
      specific QOL scores was 0.38 (95 % CI 0.03, 0.74). For cancer-specific QOL
      domains, there were positive but non-significant trends in two QOL domains
      (breast symptoms: Z score = 1.12, p = 0.26; arm symptoms: Z score = 1.32, p =
      0.19). This study provides updated findings supporting the idea that exercise
      interventions have statistically significant effects on overall QOL in breast
      cancer survivors, as well as positive trends for cancer site-specific QOL domains
      (breast and arm symptoms). 

PMID- 24569943
TI  - Tailored prolapse surgery for the treatment of haemorrhoids and obstructed
      defecation syndrome with a new dedicated device: TST STARR Plus.
AB  - OBJECTIVE: The aim of the study was to assess the safety, efficacy and
      feasibility of stapled transanal procedures performed by a new dedicated device,
      TST STARR Plus, for tailored transanal stapled surgery. METHODS: All the
      consecutive patients admitted to eight referral centres affected by prolapses
      with III-IV degrees haemorrhoids or obstructed defecation syndrome (ODS) with
      rectocele and/or rectal intussusception that underwent stapled transanal
      resection with TST STARR plus were included in the present study. Haemostatic
      stitches for bleeding of the suture line, specimen volume, operative time,
      hospital stay and perioperative complications were recorded. RESULTS: From 1
      November 2012 to 31 March 2013, 160 consecutive patients (96 females) were
      enrolled in the study. In 94 patients, the prolapse was over the half of the
      circular anal dilator (CAD). The mean duration of the procedure was 25 min. The
      mean resected volume of the specimen was 13.3 cm(3), the mean hospital stay was
      2.2 days. In 88 patients (55%), additional stitches on the suture line were
      needed (mean 2.1). Suture line dehiscence was reported in four cases, with
      intraoperative reinforcement. Bleeding was reported in seven patients (5%).
      Urgency after 30 days was reported in one patient. No major complication
      occurred. CONCLUSIONS: The new device seems to be safe and effective for a
      tailored approach to anorectal prolapse due to haemorrhoids or obstructed
      defecation.

PMID- 24569945
TI  - Assessment of solid cancer treatment feasibility in older patients: a prospective
      cohort study.
AB  - PURPOSE: To assess solid cancer treatment feasibility in older patients. METHODS:
      Between 2007 and 2010, 385 consecutive elderly patients (mean age: 78.9 +/- 5.4
      years; 47.8% males) with solid malignancies referred to two geriatric oncology
      clinics were included prospectively. We recorded feasibility of first-line
      chemotherapy (planned number of cycles in patients without metastases and three
      to six cycles depending on tumor site in patients with metastases), surgery
      (patient alive 30 days after successfully performed planned surgical procedure),
      radiotherapy (planned dose delivered), and hormonal therapy (planned drug dose
      given), and we recorded overall 1-year survival. RESULTS: Main tumor sites were
      colorectal (28.6%), breast (23.1%), and prostate (10.9%), and 47% of patients had
      metastases. Planned cancer treatment was feasible in 65.7% of patients with
      metastases; this proportion was 59.0% for chemotherapy, 82.6% for surgery, 100%
      for radiotherapy, and 85.2% for hormonal therapy. In the group without
      metastases, feasibility proportions were 86.8% overall, 72.4% for chemotherapy,
      95.7% for surgery, 96.4% for radiotherapy, and 97.9% for hormonal therapy.
      Factors independently associated with chemotherapy feasibility were good
      functional status defined as Eastern Cooperative Oncology Group performance
      status <2 (p < .0001) or activities of daily living >5 (p = .01), normal mobility
      defined as no difficulty walking (p = .01) or no fall risk (p = .007), and higher
      creatinine clearance (p = .04). CONCLUSION: Feasibility rates were considerably
      lower for chemotherapy than for surgery, radiotherapy, and hormonal therapy.
      Therefore, utilization of limited geriatric oncology resources may be optimized
      by preferential referral of elderly cancer patients initially considered for
      chemotherapy to geriatric oncology clinics.

PMID- 24569946
TI  - Effect of place of residence and treatment on survival outcomes in patients with
      diffuse large B-cell lymphoma in British Columbia.
AB  - BACKGROUND: We examined the relationship between location of residence at the
      time of diagnosis of diffuse large B-cell lymphoma (DLBCL) and health outcomes in
      a geographically large Canadian province with publicly funded, universally
      available medical care. PATIENTS AND METHODS: The British Columbia Cancer
      Registry was used to identify all patients 18-80 years of age diagnosed with
      DLBCL between January 2003 and December 2008. Home and treatment center postal
      codes were used to determine urban versus rural status and driving distance to
      access treatment. RESULTS: We identified 1,357 patients. The median age was 64
      years (range: 18-80 years), 59% were male, 50% were stage III/IV, 84% received
      chemotherapy with curative intent, and 32% received radiotherapy. There were 186
      (14%) who resided in rural areas, 141 (10%) in small urban areas, 183 (14%) in
      medium urban areas, and 847 (62%) in large urban areas. Patient and treatment
      characteristics were similar regardless of location. Five-year overall survival
      (OS) was 62% for patients in rural areas, 44% in small urban areas, 53% in medium
      urban areas, and 60% in large urban areas (p = .018). In multivariate analysis,
      there was no difference in OS between rural and large urban area patients (hazard
      ratio [HR]: 1.0; 95% confidence interval [CI]: 0.7-1.4), although patients in
      small urban areas (HR: 1.4; 95% CI: 1.0-2.0) and medium urban areas (HR: 1.4; 95%
      CI: 1.0-1.9) had worse OS than those in large urban areas. CONCLUSION: Place of
      residence at diagnosis is associated with survival of patients with DLBCL in
      British Columbia, Canada. Rural patients have similar survival to those in large
      urban areas, whereas patients living in small and medium urban areas experience
      worse outcomes.

PMID- 24569948
TI  - Mycobacterium chelonae peritonitis in peritoneal dialysis. Literature review.
AB  - Non-tuberculous mycobacteria are a rare but serious cause of peritoneal dialysis
      related peritonitis. There are no clear guidelines for treating non-tuberculous
      mycobacteria peritoneal dialysis-associated infections. It has been recommended
      that at least two antibiotics be given for a prolonged period and peritoneal
      catheter should be removed. This paper describes the clinical course and
      treatment of a patient with M. chelonae peritoneal dialysis-related peritonitis
      and reviews the previously published cases. 

PMID- 24569949
TI  - Metal free oxidative coupling of aryl formamides with alcohols for the synthesis
      of carbamates.
AB  - A direct transformation of N-aryl formamides to the corresponding carbamates via
      the formation of isocyanate intermediates is achieved in good yields using
      hypervalent iodine as an oxidant. 

PMID- 24569947
TI  - Neoadjuvant FOLFIRINOX for borderline resectable pancreas cancer: a new treatment
      paradigm?
AB  - BACKGROUND: Borderline resectable pancreatic cancer is best treated by
      multimodality therapy. FOLFIRINOX (5-fluorouracil, oxaliplatin, irinotecan, and
      leucovorin) tripled the response rate and significantly increased median survival
      for patients with advanced pancreatic cancer and shows promise for neoadjuvant
      use. Toxicity concerns prompted a careful analysis of our initial FOLFIRINOX
      experience. METHODS: All patients diagnosed with borderline resectable, biopsy
      proven pancreatic adenocarcinoma treated with neoadjuvant FOLFIRINOX between July
      2010 and December 2012 were reviewed. Primary outcome was surgical resectability.
      Secondary outcomes were treatment-related toxicities and survival. RESULTS:
      FOLFIRINOX followed by gemcitabine- or capecitabine-based chemoradiation was
      initiated in 18 patients. The most common grade 3 or 4 toxicities during
      chemotherapy were gastrointestinal, including nausea/emesis (n = 5), weight loss
      (n = 3) and diarrhea (n = 2), and hematologic (n = 2; neutropenia); five patients
      (36%) required a total of six admissions. Neoadjuvant therapy was completed in 15
      of 18 patients (83%), and 12 (67%) underwent pancreatectomy (10 Whipple, 2 total
      pancreatectomy) including portal vein resection/reconstruction in 10 (83%).
      Disease progression precluded surgery in 6 of the 18 patients (33%). All 12
      resected patients had negative (R0) margins. Only 2 of 12 (17%) were node
      positive (median node count: 26.5 [range: 15-39]). There were no in-hospital or
      30-day mortalities and no clinical pancreatic leaks or reoperations. Of the 12
      patients who completed all intended therapy, 7 (58.3%) are alive, including 5 who
      have no evidence of disease (median months from diagnosis: 22 months [range: 18
      35 months). The six patients who did not complete all planned therapy are
      deceased (months from diagnosis: 6.9-17.5 months). CONCLUSION: FOLFIRINOX
      followed by chemoradiation as neoadjuvant therapy for borderline resectable
      pancreatic adenocarcinoma is safe, and our initial experience suggests favorable
      resection rates compared with previous reports in this high-risk patient
      population.

PMID- 24569951
TI  - Magnetic resonance imaging for detection of late meniscal tears in dogs following
      tibial tuberosity advancement for treatment of cranial cruciate ligament injury.
AB  - OBJECTIVES: To document the use of and to estimate the accuracy of magnetic
      resonance (MR) imaging for detection of late meniscal tears in dogs with cranial
      cruciate ligament injury treated with tibial tuberosity advancement (TTA).
      METHODS: Medical records of dogs that had TTA followed by stifle MR imaging for
      suspected meniscal tear and subsequent arthrotomy were reviewed retrospectively.
      Magnetic resonance images were reviewed independently by an observer blinded to
      clinical information who classified menisci as torn, abnormal but intact, or
      normal. Magnetic resonance and surgical findings were compared. RESULTS: Eight
      stifles from large breed dogs were included. Six stifles had a medial meniscal
      tear identified in MR images and later confirmed surgically. In the remaining two
      stifles, the menisci appeared intact in MR images and no tear was identified at
      subsequent arthrotomy. Lateral menisci in all stifles appeared intact in MR
      images and were considered normal at surgery. Susceptibility artefacts associated
      with TTA implants were present in all images but did not adversely affect
      interpretation of intra-articular structures. CLINICAL SIGNIFICANCE: Magnetic
      resonance imaging appears to be accurate for diagnosis of late meniscal tears.
      Artefacts associated with TTA implants did not prevent evaluation of critical
      intra-articular structures. Further investigation with MR imaging should be
      considered when late meniscal tear is suspected following TTA.

PMID- 24569950
TI  - Genetic influences on political ideologies: twin analyses of 19 measures of
      political ideologies from five democracies and genome-wide findings from three
      populations.
AB  - Almost 40 years ago, evidence from large studies of adult twins and their
      relatives suggested that between 30 and 60% of the variance in social and
      political attitudes could be explained by genetic influences. However, these
      findings have not been widely accepted or incorporated into the dominant
      paradigms that explain the etiology of political ideology. This has been
      attributed in part to measurement and sample limitations, as well the relative
      absence of molecular genetic studies. Here we present results from original
      analyses of a combined sample of over 12,000 twins pairs, ascertained from nine
      different studies conducted in five democracies, sampled over the course of four
      decades. We provide evidence that genetic factors play a role in the formation of
      political ideology, regardless of how ideology is measured, the era, or the
      population sampled. The only exception is a question that explicitly uses the
      phrase "Left-Right". We then present results from one of the first genome-wide
      association studies on political ideology using data from three samples: a 1990
      Australian sample involving 6,894 individuals from 3,516 families; a 2008
      Australian sample of 1,160 related individuals from 635 families and a 2010
      Swedish sample involving 3,334 individuals from 2,607 families. No polymorphisms
      reached genome-wide significance in the meta-analysis. The combined evidence
      suggests that political ideology constitutes a fundamental aspect of one's
      genetically informed psychological disposition, but as Fisher proposed long ago,
      genetic influences on complex traits will be composed of thousands of markers of
      very small effects and it will require extremely large samples to have enough
      power in order to identify specific polymorphisms related to complex social
      traits.

PMID- 24569952
TI  - Heparin-bonded catheters for prolonging the patency of central venous catheters
      in children.
AB  - BACKGROUND: Central venous catheters (CVCs) are a mainstay in the management of
      critically ill children. However, these catheters are associated with mechanical
      and infectious complications which reduce their life span. Heparin bonding of
      catheters has shown promise in animal studies and in adults. This is the first
      update of a review published in 2007. OBJECTIVES: The primary objective was to
      determine the effect of heparin-bonded CVCs on the duration of catheter patency
      in children. Secondary objectives were to determine the effects of heparin-bonded
      catheters on catheter-related thrombosis, occlusion, blood stream infection and
      side effects. SEARCH METHODS: For this update the Cochrane Peripheral Vascular
      Diseases Group Trials Search Co-ordinator searched the Specialised Register (last
      searched August 2013) and CENTRAL (2013, Issue 7). The authors searched MEDLINE
      (1946 to week 3 August 2013). SELECTION CRITERIA: We included randomized and
      quasi-randomized controlled trials of heparin-bonded catheters versus non-heparin
      bonded catheters or antibiotic-impregnated catheters that reported on any of the
      prespecified outcomes, without language restriction. DATA COLLECTION AND
      ANALYSIS: We assessed the methodological quality of the trials using the
      information provided in the studies and by contacting authors. We extracted data
      and estimated the effect size reported as risk ratio (RR), risk difference (RD)
      or number needed to treat (NNT), as appropriate. MAIN RESULTS: We included two
      eligible studies with a total of 287 participants; both had good methodological
      quality. There was no difference in the duration of catheter patency between
      heparin-bonded and non-heparin bonded catheters (median duration seven days
      versus six days) reported in one study. There was no difference in the risk of
      catheter-related thrombosis (two studies, RR 0.34, 95% CI 0.01 to 7.68; I(2) =
      80%; RD -0.06, 95% CI -0.17 to 0.06). Data from one study revealed a
      statistically significant reduction in the risk of catheter occlusion (RR 0.06,
      95% CI 0.00 to 1.07; RD -0.08, 95% CI -0.13 to -0.02; NNT 13, 95% CI 8 to 50),
      catheter-related blood stream infections (RR 0.06, 95% CI 0.01 to 0.41; RD -0.17,
      95% CI -0.25 to -0.10; NNT 6, 95% CI 4 to 10) and catheter colonization (RR 0.21,
      95% CI 0.06 to 0.71; RD -0.11, 95% CI -0.19 to -0.04; NNT 9, 95% CI 5 to 25) in
      the heparin-bonded catheter group. The second study did not report on these
      outcomes. There was no significant difference in risk of thrombocytopenia after
      catheter placement (RR 0.73, 95% CI 0.38 to 1.39; RD -0.02, 95% CI -0.10 to
      0.07). AUTHORS' CONCLUSIONS: Two eligible studies on the use of heparin-bonded
      catheters versus placebo in children were identified. Meta-analysis of the two
      studies revealed no reduction in catheter-related thrombosis with heparin-bonded
      catheters. One study reported a reduction in catheter-related blood stream
      infection and colonization following the use of heparin-bonded catheters. The
      strength of evidence is low and further well-designed multicenter randomized
      controlled trials are warranted.

PMID- 24569955
TI  - Biosynthesis of silver nanoparticles using Bacillus subtilis EWP-46 cell-free
      extract and evaluation of its antibacterial activity.
AB  - This study highlights the ability of nitrate-reducing Bacillus subtilis EWP-46
      cell-free extract used for preparation of silver nanoparticles (AgNPs) by
      reduction of silver ions into nano silver. The production of AgNPs was optimized
      with several parameters such as hydrogen ion concentration, temperature, silver
      ion (Ag(+) ion) and time. The maximum AgNPs production was achieved at pH 10.0,
      temperature 60  degrees C, 1.0 mM Ag(+) ion and 720 min. The UV-Vis spectrum
      showed surface plasmon resonance peak at 420 nm, energy-dispersive X-ray
      spectroscopy (SEM-EDX) spectra showed the presence of element silver in pure
      form. Atomic force microscopy (AFM) and transmission electron microscopy images
      illustrated the nanoparticle size, shape, and average particle size ranging from
      10 to 20 nm. Fourier transform infrared spectroscopy provided the evidence for
      the presence of biomolecules responsible for the reduction of silver ion, and X
      ray diffraction analysis confirmed that the obtained nanoparticles were in
      crystalline form. SDS-PAGE was performed to identify the proteins and its
      molecular mass in the purified nitrate reductase from the cell-free extract. In
      addition, the minimum inhibitory concentration and minimum bactericidal
      concentration of AgNPs were investigated against gram-negative (Pseudomonas
      fluorescens) and gram-positive (Staphylococcus aureus) bacteria.

PMID- 24569954
TI  - Study of MHC class II region polymorphism in the Filipino cynomolgus macaque
      population.
AB  - The cynomolgus macaque (Macaca fascicularis) is currently used as an animal model
      in various fields of immunology especially in the development of innovative
      vaccines for the prevention and treatment of infectious diseases. The
      polymorphism of the major histocompatibility complex (MHC) influences the
      development of adaptive immune responses and it is crucial to characterize the
      polymorphism of cynomolgus MHC genes. We present here a systematic study of the
      MHC class II haplotypes in the Filipino macaque population. By the study of a
      large sample of Filipino animals (N = 353), we have characterized 18 MHC class II
      haplotypes by means of genotyping seven microsatellites. The animals were DRB
      genotyped by means of PCR-SSO or DGGE-sequencing on genomic amplified fragments.
      We cloned and sequenced the complementary DNA (cDNA) of DQA, DQB, DPA, and DPB
      genes of 117 animals. Combining the microsatellite genotyping and cDNA
      characterized in the 117 animals, we defined genetic association between the cDNA
      and the microsatellites and characterized 18 MHC class II haplotypes. For 104
      animals out of the 353 studied, the presence of a recombinant haplotype was
      highly probable. Thirty-four percent of recombination was located in 256 kb
      segment between D6S2876 and D6S2747 microsatellites, a region encompassing
      several hot spots of recombination in the human MHC. 

PMID- 24569953
TI  - Laboratory diagnosis of primary immunodeficiencies.
AB  - Primary immune deficiency disorders represent a highly heterogeneous group of
      disorders with an increased propensity to infections and other immune
      complications. A careful history to delineate the pattern of infectious organisms
      and other complications is important to guide the workup of these patients, but a
      focused laboratory evaluation is essential to the diagnosis of an underlying
      primary immunodeficiency. Initial workup of suspected immune deficiencies should
      include complete blood counts and serologic tests of immunoglobulin levels,
      vaccine titers, and complement levels, but these tests are often insufficient to
      make a diagnosis. Recent advancements in the understanding of the immune system
      have led to the development of novel immunologic assays to aid in the diagnosis
      of these disorders. Classically utilized to enumerate lymphocyte subsets, flow
      cytometric-based assays are increasingly utilized to test immune cell function
      (e.g., neutrophil oxidative burst, NK cytotoxicity), intracellular cytokine
      production (e.g., TH17 production), cellular signaling pathways (e.g., phosphor
      STAT analysis), and protein expression (e.g., BTK, Foxp3). Genetic testing has
      similarly expanded greatly as more primary immune deficiencies are defined, and
      the use of mass sequencing technologies is leading to the identification of novel
      disorders. In order to utilize these complex assays in clinical care, one must
      have a firm understanding of the immunologic assay, how the results are
      interpreted, pitfalls in the assays, and how the test affects treatment
      decisions. This article will provide a systematic approach of the evaluation of a
      suspected primary immunodeficiency, as well as provide a comprehensive list of
      testing options and their results in the context of various disease processes. 

PMID- 24569956
TI  - Standardizing benchmark dose calculations to improve science-based decisions in
      human health assessments.
AB  - BACKGROUND: Benchmark dose (BMD) modeling computes the dose associated with a
      prespecified response level. While offering advantages over traditional points of
      departure (PODs), such as no-observed-adverse-effect-levels (NOAELs), BMD methods
      have lacked consistency and transparency in application, interpretation, and
      reporting in human health assessments of chemicals. OBJECTIVES: We aimed to apply
      a standardized process for conducting BMD modeling to reduce inconsistencies in
      model fitting and selection. METHODS: We evaluated 880 dose-response data sets
      for 352 environmental chemicals with existing human health assessments. We
      calculated benchmark doses and their lower limits [10% extra risk, or change in
      the mean equal to 1 SD (BMD/L10/1SD)] for each chemical in a standardized way
      with prespecified criteria for model fit acceptance. We identified study design
      features associated with acceptable model fits. RESULTS: We derived values for
      255 (72%) of the chemicals. Batch-calculated BMD/L10/1SD values were
      significantly and highly correlated (R2 of 0.95 and 0.83, respectively, n = 42)
      with PODs previously used in human health assessments, with values similar to
      reported NOAELs. Specifically, the median ratio of BMDs10/1SD:NOAELs was 1.96,
      and the median ratio of BMDLs10/1SD:NOAELs was 0.89. We also observed a
      significant trend of increasing model viability with increasing number of dose
      groups. CONCLUSIONS: BMD/L10/1SD values can be calculated in a standardized way
      for use in health assessments on a large number of chemicals and critical
      effects. This facilitates the exploration of health effects across multiple
      studies of a given chemical or, when chemicals need to be compared, providing
      greater transparency and efficiency than current approaches.

PMID- 24569957
TI  - Fever of unknown origin in a very old patient: beware of the kidney!
AB  - ANCA-associated vasculitis affects more than 20 per million of the population per
      year and prevails in the elderly. Renal involvement, either isolated or in the
      context of systemic vasculitis, is common. We report the case of an 86-year-old
      patient who presented with a histologically proven renal limited vasculitis and
      with fever and fatigue but with normal renal function and urine analysis. Serum
      creatinine increased and microscopic hematuria became evident only 3 weeks after
      symptoms onset, whereas ANCA positivity was the only early key to the diagnosis.
      This case shows that in the elderly an ANCA-related pauci-immune
      glomerulonephritis in its earliest stages should be suspected in the presence of
      a fever of unknown origin even if serum and urine analyses are normal. 

PMID- 24569960
TI  - Extracorporeal photopheresis versus standard treatment for acute graft-versus
      host disease after haematopoietic stem cell transplantation in paediatric
      patients.
AB  - BACKGROUND: Acute graft-versus host disease (aGvHD) is a major cause of morbidity
      and mortality after haematopoietic stem cell transplantation (HSCT) occurring in
      8% to 59% of the recipients. Currently, the therapeutic mainstay for aGvHD is
      corticosteroids. However, there is no established standard treatment for steroid
      refractory aGvHD. Extracorporeal photopheresis (ECP) is a type of
      immunomodulatory method amongst different therapeutic options that involves ex
      vivo collection of peripheral mononuclear cells, exposure to the photoactive
      agent 8-methoxypsoralen and ultraviolet-A radiation, and re-infusion of these
      treated blood cells to the patient. The mechanisms of action of ECP are not
      completely understood OBJECTIVES: To evaluate the effectiveness and safety of ECP
      for the management of aGvHD in children and adolescents after HSCT. SEARCH
      METHODS: We searched the Cochrane Central Register of Controlled Trials (Issue 9,
      2012), MEDLINE/PubMed and EMBASE (Ovid) databases from their inception to 12
      September 2012. We searched the reference lists of potentially relevant studies
      without any language restriction. We searched eight trial registers and four
      conference proceedings. We also contacted an expert in the field to request
      information on unpublished study that involves ECP in aGvHD after HSCT. SELECTION
      CRITERIA: Randomised controlled trials (RCTs) comparing ECP with or without
      standard treatment versus standard treatment alone in paediatric patients with
      aGvHD after HSCT. DATA COLLECTION AND ANALYSIS: Two review authors independently
      performed the study selection. We resolved disagreement in the selection of
      trials by consultation with a third review author. MAIN RESULTS: We found no
      studies meeting the criteria for inclusion in this review. AUTHORS' CONCLUSIONS:
      The efficacy of ECP in the treatment of aGvHD in paediatric patients after HSCT
      is unknown and its use should be restricted within the context of RCTs. Such
      studies should address a comparison of ECP alone or in combination with standard
      treatment versus standard treatment alone. 

PMID- 24569961
TI  - Extracorporeal photopheresis versus alternative treatment for chronic graft
      versus-host disease after haematopoietic stem cell transplantation in paediatric
      patients.
AB  - BACKGROUND: Chronic graft-versus-host disease (GvHD) is a major cause of
      morbidity and mortality after haematopoietic stem cell transplantation occurring
      in 6% to 65% of the recipients. Currently, the therapeutic mainstay for chronic
      GvHD are corticosteroids that are frequently combined with other
      immunosuppressive agents in people with steroid-refractory manifestations. There
      is no established standard treatment for steroid-refractory chronic GvHD. The
      therapeutic options in these people include extracorporeal photopheresis (ECP),
      an immunomodulatory treatment that involves ex vivo collection of mononuclear
      cells from peripheral blood, exposure to the photoactive agent 8-methoxypsoralen,
      ultraviolet radiation and re-infusion of the processed cell product. The
      mechanisms of action of ECP are not completely understood. OBJECTIVES: To
      evaluate the effectiveness and safety of ECP for the management of chronic GvHD
      in children and adolescents after haematopoietic stem cell transplantation.
      SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials
      (Issue 9, 2012), MEDLINE and EMBASE databases from their inception to 12
      September 2012. We searched the reference lists of potentially relevant studies
      without any language restriction. We searched eight trial registers and five
      conference proceedings. We also contacted experts in the field. SELECTION
      CRITERIA: Randomised controlled trials (RCTs) comparing ECP with or without
      alternative treatment versus alternative treatment alone in paediatric patients
      with chronic GvHD after haematopoietic stem cell transplantation. DATA COLLECTION
      AND ANALYSIS: Two review authors independently performed the study selection. We
      resolved disagreements in the selection of trials by consultation with a third
      review author. MAIN RESULTS: We found no studies meeting the criteria for
      inclusion in this review. AUTHORS' CONCLUSIONS: The efficacy of ECP in the
      treatment of chronic GvHD in paediatric patients after haematopoietic stem cell
      transplantation based on RCTs can currently not be evaluated since we have found
      no such studies. Current recommendations are based on retrospective or
      observational studies only. Thus, ideally, ECP should be applied in the context
      of controlled trials only. However, performing RCTs in this patient population
      will be challenging due to the limited number of patients, the variable disease
      presentation and the lack of well-defined response criteria. International
      collaboration, multicentre trials and appropriate funding for such trials will be
      needed. If treatment decisions based on clinical grounds in favour of ECP are
      made, people should be carefully monitored for beneficial and harmful effects and
      efforts should be made to share this information with other clinicians, for
      example by setting up registries for paediatric patients that are treated with
      ECP.

PMID- 24569962
TI  - Organocatalytic [4 + 2] cyclocondensation of alpha,beta-unsaturated acyl
      chlorides with imines: highly enantioselective synthesis of dihydropyridinone and
      piperidine derivatives.
AB  - The cinchona alkaloid-catalyzed [4 + 2] cyclocondensation of alpha,beta
      unsaturated acyl chlorides with imines is developed to give the corresponding
      substituted dihydropyridinones in good yields with high to excellent
      enantioselectivities. Reduction of the dihydropyridinones gave highly optically
      active substituted tetrahydropyridinone and piperidine derivatives. 

PMID- 24569964
TI  - Social determinants of health in the Americas.

PMID- 24569963
TI  - Overexpression of genes involved in miRNA biogenesis in medullary thyroid
      carcinomas with RET mutation.
AB  - Abnormal expression of non-coding micro RNA (miRNA) has been described in
      medullary thyroid carcinoma (MTC). Expression of genes encoding factors involved
      in miRNA biogenesis results often deregulated in human cancer and correlates with
      aggressive clinical behavior. In this study, expression of four genes involved in
      miRNA biogenesis (DICER, DROSHA, DCGR8, and XPO5) was investigated in 54
      specimens of MTC. Among them, 33 and 13 harbored RET and RAS mutations,
      respectively. DICER, DGCR8, and XPO5 mRNA levels were significantly overexpressed
      in MTC harboring RET mutations, in particular, in the presence of RET634
      mutation. When MTCs with RET and RAS mutations were compared, only DGCR8
      displayed a significant difference, while MTCs with RAS mutations did not show
      significant differences with respect to non-mutated tumors. We then attempted to
      correlate expression of miRNA biogenesis genes with tumor aggressiveness.
      According to the TNM status, MTCs were divided in two groups and compared (N0 M0
      vs. N1 and/or M1): for all four genes no significant difference was detected.
      Cell line experiments, in which expression of a RET mutation is silenced by
      siRNA, suggest the existence of a causal relationship between RET mutation and
      overexpression of DICER, DGCR8, and XPO5 genes. These findings demonstrate that
      RET- but not RAS-driven tumorigenic alterations include abnormalities in the
      expression of some important genes involved in miRNA biogenesis that could
      represent new potential markers for targeted therapies in the treatment of RET
      mutated MTCs aimed to restore the normal miRNA expression profile.

PMID- 24569965
TI  - Action on social determinants of health in the Americas.

PMID- 24569967
TI  - [How does type of health insurance affect receipt of Pap testing in Peru?].
AB  - OBJECTIVE: Describe the association between receipt of cervical cytology and type
      of health insurance in Peruvian women, and determine the role of sociodemographic
      and sexual health variables in this relationship. METHODS: A cross-sectional
      study using information on a sample of 12 272 women aged 30 to 49 years from the
      Demographic and Family Health Survey (ENDES), Peru, 2005-2008. The dependent
      variable was receipt of at least one Pap smear in the last five years. The
      primary independent variables were type of health insurance, educational level,
      household socioeconomic level, ethnicity, and place of residence. Prevalence
      ratio, obtained from Poisson regression with robust variance, was used to measure
      multivariate association. RESULTS: Among sexually active women, 62.7% had
      received at least one Pap test in the last five years. Percentage of women tested
      varied by type of health insurance. Women with public or private insurance had a
      greater probability of having received a Pap smear--1.27 (95% CI, 1.24-1.31) and
      1.52 (95% CI, 1.46-1.58) times greater, respectively--than uninsured women. This
      association was primarily explained by socioeconomic status variables. In
      addition, women who participated the least in screening were characterized by
      illiteracy or only a primary education, low socioeconomic level, speaking an
      indigenous language, and living in a rural area. When they also lacked health
      insurance, the gap widened, rising to as much as one third compared to more
      advantaged social groups. CONCLUSIONS: Inequalities were found in receipt of Pap
      testing according to type of health insurance; women without insurance were least
      likely to be screened, implying existence of a barrier to cervical cancer
      screening in Peru.

PMID- 24569966
TI  - Gender differences in the effects of urban neighborhood on depressive symptoms in
      Jamaica.
AB  - OBJECTIVE: To explore the mental health effects of the urban neighborhood on men
      and women in Jamaica and the implications for urban planning and social
      development. METHODS: A cross-sectional household sample of 2 848 individuals 15
      74 years of age obtained from the Jamaica Health and Lifestyle Survey 2007-2008
      was analyzed. Secondary analysis was undertaken by developing composite scores to
      describe observer recorded neighborhood features, including infrastructure,
      amenities/services, physical conditions, community socioeconomic status, and
      green spaces around the home. Depressive symptoms were assessed using the
      Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). Bivariate and
      multivariate methods were used to explore the associations among gender,
      neighborhood factors, and risk of depressive symptoms. RESULTS: While no
      associations were found among rural residents, urban neighborhoods were
      associated with increased risk of depressive symptoms. Among males, residing in a
      neighborhood with poor infrastructure increased risk; among females, residing in
      an informal community/unplanned neighborhood increased risk. CONCLUSIONS: The
      urban neighborhood contributes to the risk of depression symptomatology in
      Jamaica, with different environmental stressors affecting men and women. Urban
      and social planners need to consider the physical environment when developing
      health interventions in urban settings, particularly in marginalized communities.

PMID- 24569968
TI  - [Inequalities in oral health care use in the primary care setting and associated
      factors in two Brazilian municipalities].
AB  - OBJECTIVE: To investigate the factors associated with inequality in the use of
      oral health services in the Brazilian Family Health Program (Estrategia Saude da
      Familia, ESF) as measured by dental extractions. METHODS: A population-based
      household survey was carried out in two municipalities with full coverage by the
      ESF in the state of Bahia, Brazil. Ten census tracts were randomly selected.
      Households were selected by systematic sampling. To assess the use of public
      services by the population, a prevalence of 50%, sampling error of 4%, and
      confidence interval of 95% were considered. Trained community health workers
      conducted key informant interviews on use of oral health services and collected
      demographic data for all household members aged 15 years or older. Dental
      extraction was the main outcome. The association between dental extraction and
      predictive variables was assessed using prevalence ratio, and multivar logistic
      regression analysis was performed using odds ratio (OR). RESULTS: Data from 2,539
      people was collected. Of these, 682 (26.86%) had used primary oral health care
      services in the previous 12 months. Dental extraction was performed in 218
      (31.96%) out of 682 primary care patients. Being assisted by social programs (OR
      = 1.43; IC95%: 1.02-2.01), being older than 35 years (OR = 1.59; IC95%: 1.12
      2.27), and having lower education levels (OR = 1.81; IC95%: 1.27-2.56) were
      independently associated with the outcome. CONCLUSIONS: The present results
      suggest that historical inequalities of access to oral health services persist.
      Intersectoral actions may play an important role in improving oral health
      conditions.

PMID- 24569969
TI  - Linking evidence to action on social determinants of health using Urban HEART in
      the Americas.
AB  - OBJECTIVE: To evaluate the experience of select cities in the Americas using the
      Urban Health Equity Assessment and Response Tool (Urban HEART) launched by the
      World Health Organization in 2010 and to determine its utility in supporting
      government efforts to improve health equity using the social determinants of
      health (SDH) approach. METHODS: The Urban HEART experience was evaluated in four
      cities from 2010-2013: Guarulhos (Brazil), Toronto (Canada), and Bogota and
      Medellin (Colombia). Reports were submitted by Urban HEART teams in each city and
      supplemented by first-hand accounts of key informants. The analysis considered
      each city's networks and the resources it used to implement Urban HEART; the
      process by which each city identified equity gaps and prioritized interventions;
      and finally, the facilitators and barriers encountered, along with next steps.
      RESULTS: In three cities, local governments spearheaded the process, while in the
      fourth (Toronto), academia initiated and led the process. All cities used Urban
      HEART as a platform to engage multiple stakeholders. Urban HEART's Matrix and
      Monitor were used to identify equity gaps within cities. While Bogota and
      Medellin prioritized among existing interventions, Guarulhos adopted new
      interventions focused on deprived districts. Actions were taken on intermediate
      determinants, e.g., health systems access, and structural SDH, e.g., unemployment
      and human rights. CONCLUSIONS: Urban HEART provides local governments with a
      simple and systematic method for assessing and responding to health inequity.
      Through the SDH approach, the tool has provided a platform for intersectoral
      action and community involvement. While some areas of guidance could be
      strengthened, Urban HEART is a useful tool for directing local action on health
      inequities, and should be scaled up within the Region of the Americas, building
      upon current experience.

PMID- 24569970
TI  - [Governance, sustainability, and equity in the health program for the
      municipality of Sao Jose dos Pinhais, Brazil].
AB  - OBJECTIVE: To analyze the Final Report of the VIII Health Conference and the Sao
      Jose dos Pinhais City Health Program for 2010-2013 and investigate whether these
      documents addressed the themes of sustainability, governance, and equity and the
      interfaces between these themes--government policies, power balance, and
      inclusive processes/impacting results--that make up the Concept Model for Human
      Development and Health Promotion developed by the authors. METHOD: This case
      study analyzed 331 proposals approved for incorporation in the City Health
      Program. The six thematical categories of the Concept Model were analyzed using
      ATLAS Ti 5.0 software. The proposals were classified according to the number of
      themes and interfaces of the Concept Model: full health proposals contained all
      six categories; partial proposals contained three categories; and incipient
      proposals contained one category. RESULTS: Of 331 proposals approved, 162 (49%)
      contemplated the six thematical categories and were classified as full health
      promotion proposals. Ninety-five (29%) contemplated three categories (partial
      health promotion). Of these, 38 (12%) addressed Governance, Sustainability, and
      Government Policies, 33 (10%) addressed Governance, Power Balance, and Equity and
      24 (7%) addressed Equity, Inclusive Processes/Impact Results, and Sustainability.
      Finally, 74 (22%) proposals contemplated only one category and were classified as
      incipient: 36 (11%) addressed Governance, 27 (8%) addressed sustainability, and
      11 (3%) addressed equity. CONCLUSIONS: Based on the fact that 49% of the
      proposals approved were classified as full health promotion, it is considered
      that the effectiveness of social control and popular participation in the
      construction of health policies at the local level contritute to the promotion of
      health in the city.

PMID- 24569971
TI  - Measuring progress of collaborative action in a community health effort.
AB  - OBJECTIVE: To measure the progress made by the collaborative actions of
      multisectorial partners in a community health effort using a systematic method to
      document and evaluate community/system changes over time. METHODS: This was a
      community-based participatory research project engaging community partners of the
      Latino Health for All Coalition, which based on the Health for All model,
      addresses health inequity in a low-income neighborhood in Kansas City, Kansas,
      United States of America. Guided by three research questions regarding the extent
      to which the Coalition catalyzed change, intensity of change, and how to visually
      display change, data were collected on community/system changes implemented by
      the community partners from 2009-2012. These changes were characterized and rated
      according to intensity (event duration, population reach, and strategy) and by
      other categories, such as social determinant of health mechanism and sector.
      RESULTS: During the 4-year study period, the Coalition implemented 64
      community/system changes. These changes were aligned with the Coalition's primary
      goals of healthy nutrition, physical activity, and access to health screenings.
      Community/system efforts improved over time, becoming longer in duration and
      reaching more of the population. CONCLUSIONS: Although evidence of its predictive
      validity awaits further research, this method for documenting and characterizing
      community/system changes enables community partners to see progress made by their
      health initiatives.

PMID- 24569972
TI  - [Social exclusion and health inequity: a case study based on a cash distribution
      program (Bolsa Familia) in Brazil].
AB  - OBJECTIVE: To understand the impact of Bolsa Familia (PBF), a federal cash
      transfer program, and to analyze its effects on social inclusion and exclusion
      processes experienced by low-income families in Brazil, with a focus on the
      program's potential to help overcome health inequity. METHODS: This qualitative
      investigation used a case study methodology including observant participation,
      review of documents, and semi-structured interviews with current and former PBF
      beneficiaries, as well as with the program's local managers. The study was
      conducted in a small city in the state of Rio de Janeiro with a high social
      exclusion index and 100% coverage by the Family Health Strategy (Estrategia Saude
      da Familia, ESF) program. The economic, political, social, and cultural
      dimensions of social exclusion and inclusion processes were used to guide data
      collection and analysis. RESULTS: The program facilitated social inclusion of low
      income families, especially in the economic and social dimensions. Nevertheless,
      it did not produce the changes desired by the beneficiaries in the work
      dimension. The effects on the political dimension were limited by the
      insufficient social engagement of the PBF. The interviewees underscored the
      positive effects of the ESF, which allowed them to exercise their right to health
      by granting them wider access to primary health care services. However, these
      effects appeared to be unrelated to the PBF. CONCLUSIONS: The results reveal
      effects, limitations, and challenges of the PBF towards modifying the social
      determinants of health inequity, in order to promote more effective changes in
      the social exclusion/inclusion dynamics affecting low-income families.

PMID- 24569974
TI  - [Social determinants and self-reported tuberculosis: National Research by
      Household Sample, metropolitan areas, Brazil].
AB  - OBJECTIVE: To verify the association between individual demographic and
      socioeconomic variables and the incidence of self-reported tuberculosis in
      Brazil. METHODS: This cross-sectional study used data from the health supplement
      of the 2008 National Research by Household Sample (PNAD) for Brazil's
      metropolitan areas. An analysis was done of the association between demographic,
      social, and health service use variables and the odds of having been diagnosed
      with tuberculosis, according to data from PNAD. Socioeconomic status was assessed
      based on per capita household income, educational attainment, race, and number of
      persons per bedroom. Having a place of reference for health care and having
      health insurance were used as proxy for access to health care, and having been to
      a doctor in the previous 12 months was used as a variable of health service use.
      Due to the complex sample design of PNAD, logistic regression was used, taking
      into account the design effect. RESULTS: The odds of being diagnosed with
      tuberculosis increased with age and were greater among men. Within the nine
      metropolitan areas, the effect of income was observed starting at half the
      minimum wage, with odds decreasing as income increased. Not having seen a doctor
      in the previous year and having finished high school reduced the odds of
      reporting tuberculosis by 60%. CONCLUSIONS: Improving the living conditions of
      vulnerable population segments and facilitating their access to diagnosis should
      be primary strategies for controlling tuberculosis.

PMID- 24569973
TI  - [Social determinants of dropout from diagnosis and treatment by women with
      abnormal Pap smears in Buenos Aires, Argentina].
AB  - OBJECTIVE: Determine the extent and reasons why women with abnormal Pap smears
      drop out from diagnosis and treatment, and the relationship between women's
      socioeconomic characteristics and dropping out. METHODS: Cross-sectional
      retrospective study. Analysis of secondary sources and household interviews with
      women with abnormal Pap smears seen in the public municipal system from 2009 to
      2011. RESULTS: Confirmed dropout in the study population was 18.3%. Women with
      the greatest probability of dropping out lived in homes where there were children
      under five (probability ratio [PR]: 2.4; 95% confidence interval [95%CI]: 1.2
      4.8) and where there was overcrowding (PR: 2.9; 95%CI: 1.2-7.3). Women whose
      initial Pap smear was done in a primary care center had a 4.6 times greater
      probability of dropping out than those seen in a hospital (95%CI: 1.7-12.3). The
      main reasons reported for dropping out were problems with health services
      organization and domestic workload. CONCLUSIONS: Women's living conditions and
      the organization and quality of health services affect dropout from diagnosis and
      treatment of precancerous lesions. Strategies need to be developed that address
      social determinants of dropping out as a way to ensure effectiveness of cervical
      cancer screening programs.

PMID- 24569975
TI  - [Use of indicators of geographical accessibility to primary health care centers
      in addressing inequities].
AB  - OBJECTIVE: Characterize geographical indicators in relation to their usefulness
      in measuring regional inequities, identify and describe areas according to their
      degree of geographical accessibility to primary health care centers (PHCCs), and
      detect populations at risk from the perspective of access to primary care.
      METHODS: Analysis of spatial accessibility using geographic information systems
      (GIS) involved three aspects: population without medical coverage, distribution
      of PHCCs, and the public transportation network connecting them. RESULTS: The
      development of indicators of demand (real, potential, and differential) and
      analysis of territorial factors affecting population mobility enabled the
      characterization of PHCCs with regard to their environment, thereby contributing
      to local and regional analysis and to the detection of different zones according
      to regional connectivity levels. CONCLUSIONS: Indicators developed in a GIS
      environment were very useful in analyzing accessibility to PHCCs by vulnerable
      populations. Zoning the region helped identify inequities by differentiating
      areas of unmet demand and fragmentation of spatial connectivity between PHCCs and
      public transportation.

PMID- 24569976
TI  - Health systems in context: a systematic review of the integration of the social
      determinants of health within health systems frameworks.
AB  - OBJECTIVE: To systematically review and analyze various ways that health systems
      frameworks interact with the social determinants of health (SDH), as well as the
      implications of these interactions. METHODS: This was a review of the literature
      conducted in 2012 using predetermined criteria to search three comprehensive
      databases (PubMed, the Cochrane Database for Systematic Reviews, and the World
      Bank E-Library) and grey literature for articles with any consideration of the
      SDH within health systems frameworks. Snowball sampling and expert opinion were
      used to include any potentially relevant articles not identified by the initial
      search. In total, 4,152 documents were found; of these, 27 were included in the
      analyses. RESULTS: Five main categories of interaction between health systems and
      SDH emerged: Bounded, Production, Reciprocal, Joint, and Systems models. At one
      end were the Bounded and Production models, which conceive the SDH to be outside
      the health system; at the other end, the Joint and Systems models, which
      visualize a continuous and dynamic interaction. CONCLUSIONS: Considering the
      complex and dynamic interactions among different kinds of organizations involved
      in and with the health system,the Joint and Systems models seem to best reflect
      these interactions, and should thereby guide stakeholders in planning for change.

PMID- 24569977
TI  - Integrating social determinants of health in the universal health coverage
      monitoring framework.
AB  - Underpinning the global commitment to universal health coverage (UHC) is the
      fundamental role of health for well-being and sustainable development. UHC is
      proposed as an umbrella health goal in the post-2015 sustainable development
      agenda because it implies universal and equitable effective delivery of
      comprehensive health services by a strong health system, aligned with multiple
      sectors around the shared goal of better health. In this paper, we argue that
      social determinants of health (SDH) are central to both the equitable pursuit of
      healthy lives and the provision of health services for all and, therefore, should
      be expressly incorporated into the framework for monitoring UHC. This can be done
      by: (a) disaggregating UHC indicators by different measures of socioeconomic
      position to reflect the social gradient and the complexity of social
      stratification; and (b) connecting health indicators, both outcomes and coverage,
      with SDH and policies within and outside of the health sector. Not locating UHC
      in the context of action on SDH increases the risk of going down a narrow route
      that limits the right to health to coverage of services and financial protection.

PMID- 24569978
TI  - Synergy for health equity: integrating health promotion and social determinants
      of health approaches in and beyond the Americas.
AB  - Health promotion and social determinants of health approaches, when integrated,
      can better contribute to understanding and addressing health inequities. Yet,
      they have typically been pursued as two solitudes. This paper presents the key
      elements, principles, actions, and potential synergies of these complementary
      frameworks for addressing health equity. The value-added of integrating these two
      approaches is illustrated by three examples drawn from the authors' experiences
      in the Americas: at the community level, through a community-based coalition for
      reducing chronic disease disparities among minorities in an urban center in the
      United States; at the national level, through healthy-settings interventions in
      Canada; and at the Regional level, through health cooperation based on social
      justice values in Latin America. Challenges to integrating health promotion and
      social determinants of health approaches in the Americas are also discussed. 

PMID- 24569979
TI  - Spectrin and phospholipids - the current picture of their fascinating interplay.
AB  - The spectrin-based membrane skeleton is crucial for the mechanical stability and
      resilience of erythrocytes. It mainly contributes to membrane integrity, protein
      organization and trafficking. Two transmembrane protein macro-complexes that are
      linked together by spectrin tetramers play a crucial role in attaching the
      membrane skeleton to the cell membrane, but they are not exclusive. Considerable
      experimental data have shown that direct interactions between spectrin and
      membrane lipids are important for cell membrane cohesion. Spectrin is a
      multidomain, multifunctional protein with several distinctive structural regions,
      including lipid-binding sites within CH tandem domains, a PH domain, and triple
      helical segments, which are excellent examples of ligand specificity hidden in a
      regular repetitive structure, as recently shown for the ankyrin-sensitive lipid
      binding domain of beta spectrin. In this review, we summarize the state of
      knowledge about interactions between spectrin and membrane lipids.

PMID- 24569980
TI  - Myricetin blocks lipoteichoic acid-induced COX-2 expression in human gingival
      fibroblasts.
AB  - Periodontitis is an infectious disease caused by microorganisms present in dental
      bacterial plaque. Lipoteichoic acid (LTA) is a component of the external membrane
      of Gram-positive bacteria. It causes septic shock. Ingested flavonoids have been
      reported to directly affect the regulation of cyclooxygenase-2 (COX-2) expression
      induced by bacterial toxins. In this study, we examined the effects of four
      flavonoids (luteolin, fisetin, morin and myricetin) on the activation of ERK1/2,
      p38 and AKT, and on the synthesis of COX-2 in human gingival fibroblasts treated
      with LTA from Streptococcus sanguinis. We found that luteolin and myricetin
      blocked AKT and p38 activation and that myricetin blocked LTA-induced COX-2
      expression. The results of our study are important for elucidating the mechanism
      of action of flavonoid regulation of inflammatory responses.

PMID- 24569981
TI  - Gene expression profiles of various cytokines in mesenchymal stem cells derived
      from umbilical cord tissue and bone marrow following infection with human
      cytomegalovirus.
AB  - Mesenchymal stem cells (MSCs) have both multi-lineage differentiation potential
      and immunosuppressive properties, making them ideal candidates for regenerative
      medicine. However, their immunosuppressive properties potentially increase the
      risk of cancer progression and opportunistic infections. In this study, MSCs
      isolated from human umbilical cord blood (UCMSCs) and adult bone marrow (BMMSCs)
      were infected with human cytomegalovirus (HCMV). Cytopathic changes were observed
      10 days post infection. PCR products amplified from genomic DNA and cDNA were
      used to confirm the HCMV infection of the UCMSCs and BMMSCs. Real-time PCR was
      conducted to quantify the expression of immunomodulatory molecules, including
      cytokines, chemokines, growth factors, adhesion molecules and cancer-related
      genes. Our results indicate high upregulation of the majority of these molecules,
      including many growth factors, tumor necrosis factor alpha, interleukin-8,
      interleukin-6 and interferon gamma. Adhesion molecules (VCAM-1, TCAM-1 and
      selectin-E) were downregulated in the infected UCMSCs and BMMSCs. Antibody chip
      array evaluation of cell culture media indicated that the growth factor secretion
      by UCMSCs and BMMSCs was greatly influenced (p < 0.001) by HCMV. The stimulation
      of MSCs with HCMV led to the activation of downstream signaling pathways,
      including pSTAT3 and Wnt2. Our results show that HCMV can significantly alter the
      functions of both UCMSCs and BMMSCs, although not in the same way or to the same
      extent. In both cases, there was an increase in the expression of proangiogenic
      factors in the microenvironment following HMCV infection. The discrepancy between
      the two cell types may be explained by their different developmental origin,
      although further analysis is necessary. Future studies should decipher the
      underlying mechanism by which HCMV controls MSCs, which may lead to the
      development of new therapeutic treatments.

PMID- 24569982
TI  - Management and medicine: why we need a new approach to the relationship.
AB  - New Public Management has affected the relationship between corporate
      managerialism and professional modes of governing hospitals. While doctors'
      increasing involvement in management may have positive effects on health care,
      hospital governance, health care policies and medical education have largely
      failed to support this change. There is a need for new policies and approaches to
      support the changing connections between medicine and management that abandons
      both the military discourse of 'wars' and 'battlefields' and the new rhetoric of
      'clinical leadership'.

PMID- 24569983
TI  - The color lexicon of American English.
AB  - This article describes color naming by 51 American English-speaking informants. A
      free-naming task produced 122 monolexemic color terms, with which informants
      named the 330 Munsell samples from the World Color Survey. Cluster analysis
      consolidated those terms into a glossary of 20 named color categories: the 11
      Basic Color Term (BCT) categories of Berlin and Kay (1969, p. 2) plus nine
      nonbasic chromatic categories. The glossed data revealed two color-naming motifs:
      the green-blue motif of the World Color Survey and a novel green-teal-blue motif,
      which featured peach, teal, lavender, and maroon as high-consensus terms. Women
      used more terms than men, and more women expressed the novel motif. Under a
      constrained-naming protocol, informants supplied BCTs for the color samples
      previously given nonbasic terms. Most of the glossed nonbasic terms from the free
      naming task named low-consensus colors located at the BCT boundaries revealed by
      the constrained-naming task. This study provides evidence for continuing
      evolution of the color lexicon of American English, and provides insight into the
      processes governing this evolution. 

PMID- 24569984
TI  - Unsupervised clustering method to detect microsaccades.
AB  - Microsaccades, small involuntary eye movements that occur once or twice per
      second during attempted visual fixation, are relevant to perception, cognition,
      and oculomotor control and present distinctive characteristics in visual and
      oculomotor pathologies. Thus, the development of robust and accurate microsaccade
      detection techniques is important for basic and clinical neuroscience research.
      Due to the diminutive size of microsaccades, however, automatic and reliable
      detection can be difficult. Current challenges in microsaccade detection include
      reliance on set, arbitrary thresholds and lack of objective validation. Here we
      describe a novel microsaccade-detecting method, based on unsupervised clustering
      techniques, that does not require an arbitrary threshold and provides a detection
      reliability index. We validated the new clustering method using real and
      simulated eye-movement data. The clustering method reduced detection errors by
      62% for binocular data and 78% for monocular data, when compared to standard
      contemporary microsaccade-detection techniques. Further, the clustering method's
      reliability index was correlated with the microsaccade-detection error rate,
      suggesting that the reliability index may be used to determine the comparative
      precision of eye-tracking devices. 

PMID- 24569985
TI  - The development of global motion discrimination in school aged children.
AB  - Global motion perception matures during childhood and involves the detection of
      local directional signals that are integrated across space. We examine the
      maturation of local directional selectivity and global motion integration with an
      equivalent noise paradigm applied to direction discrimination. One hundred and
      three observers (6-17 years) identified the global direction of motion in a 2AFC
      task. The 8 degrees  central stimuli consisted of 100 dots of 10% Michelson
      contrast moving 2.8 degrees /s or 9.8 degrees /s. Local directional selectivity
      and global sampling efficiency were estimated from direction discrimination
      thresholds as a function of external directional noise, speed, and age. Direction
      discrimination thresholds improved gradually until the age of 14 years (linear
      regression, p < 0.05) for both speeds. This improvement was associated with a
      gradual increase in sampling efficiency (linear regression, p < 0.05), with no
      significant change in internal noise. Direction sensitivity was lower for dots
      moving at 2.8 degrees /s than at 9.8 degrees /s for all ages (paired t test, p <
      0.05) and is mainly due to lower sampling efficiency. Global motion perception
      improves gradually during development and matures by age 14. There was no change
      in internal noise after the age of 6, suggesting that local direction selectivity
      is mature by that age. The improvement in global motion perception is underpinned
      by a steady increase in the efficiency with which direction signals are pooled,
      suggesting that global motion pooling processes mature for longer and later than
      local motion processing. 

PMID- 24569986
TI  - Spatial biases in viewing behavior.
AB  - Viewing behavior exhibits temporal and spatial structure that is independent of
      stimulus content and task goals. One example of such structure is horizontal
      biases, which are likely rooted in left-right asymmetries of the visual and
      attentional systems. Here, we studied the existence, extent, and mechanisms of
      this bias. Left- and right-handed subjects explored scenes from different image
      categories, presented in original and mirrored versions. We also varied the
      spatial spectral content of the images and the timing of stimulus onset. We found
      a marked leftward bias at the start of exploration that was independent of image
      category. This left bias was followed by a weak bias to the right that persisted
      for several seconds. This asymmetry was found in the majority of right-handers
      but not in left-handers. Neither low- nor high-pass filtering of the stimuli
      influenced the bias. This argues against mechanisms related to the hemispheric
      segregation of global versus local visual processing. Introducing a delay in
      stimulus onset after offset of a central fixation spot also had no influence. The
      bias was present even when stimuli were presented continuously and without any
      requirement to fixate, associated to both fixation- and saccade-contingent image
      changes. This suggests the bias is not caused by structural asymmetries in
      fixation control. Instead the pervasive horizontal bias is compatible with known
      asymmetries of higher-level attentional areas related to the detection of novel
      events. 

PMID- 24569987
TI  - Hyperglycemia diverts dividing osteoblastic precursor cells to an adipogenic
      pathway and induces synthesis of a hyaluronan matrix that is adhesive for
      monocytes.
AB  - Isolated rat bone marrow stromal cells cultured in osteogenic medium in which the
      normal 5.6 mm glucose is changed to hyperglycemic 25.6 mm glucose greatly
      increase lipid formation between 21-31 days of culture that is associated with
      decreased biomineralization, up-regulate expression of cyclin D3 and two
      adipogenic markers (CCAAT/enhancer binding protein alpha and peroxisome
      proliferator-activated receptor gamma) within 5 days of culture, increase neutral
      and polar lipid synthesis within 5 days of culture, and form a monocyte-adhesive
      hyaluronan matrix through an endoplasmic reticulum stress-induced autophagic
      mechanism. Evidence is also provided that, by 4 weeks after diabetes onset in the
      streptozotocin-induced diabetic rat model, there is a large loss of trabecular
      bone mineral density without apparent proportional changes in underlying collagen
      matrices, a large accumulation of a hyaluronan matrix within the trabecular bone
      marrow, and adipocytes and macrophages embedded in this hyaluronan matrix. These
      results support the hypothesis that hyperglycemia in bone marrow diverts dividing
      osteoblastic precursor cells (bone marrow stromal cells) to a metabolically
      stressed adipogenic pathway that induces synthesis of a hyaluronan matrix that
      recruits inflammatory cells and establishes a chronic inflammatory process that
      demineralizes trabecular cancellous bone. 

PMID- 24569988
TI  - The mitochondrial intermembrane space oxireductase Mia40 funnels the oxidative
      folding pathway of the cytochrome c oxidase assembly protein Cox19.
AB  - Mia40-catalyzed disulfide formation drives the import of many proteins into the
      mitochondria. Here we characterize the oxidative folding of Cox19, a twin CX9C
      Mia40 substrate. Cox19 oxidation is extremely slow, explaining the persistence of
      import-competent reduced species in the cytosol. Mia40 accelerates Cox19 folding
      through the specific recognition of the third Cys in the second helical CX9C
      motif and the subsequent oxidation of the inner disulfide bond. This renders a
      native-like intermediate that oxidizes in a slow uncatalyzed reaction into native
      Cox19. The same intermediate dominates the pathway in the absence of Mia40, and
      chemical induction of an alpha-helical structure by trifluoroethanol suffices to
      accelerate productive folding and mimic the Mia40 folding template mechanism. The
      Mia40 role is to funnel a rough folding landscape, skipping the accumulation of
      kinetic traps, providing a rationale for the promiscuity of Mia40. 

PMID- 24569989
TI  - N-terminal isoforms of the large-conductance Ca2+-activated K+ channel are
      differentially modulated by the auxiliary beta1-subunit.
AB  - The large-conductance Ca(2+)-activated K(+) (BK(Ca)) channel is essential for
      maintaining the membrane in a hyperpolarized state, thereby regulating neuronal
      excitability, smooth muscle contraction, and secretion. The BK(Ca) alpha-subunit
      has three predicted initiation codons that generate proteins with N-terminal ends
      starting with the amino acid sequences MANG, MSSN, or MDAL. Because the N
      terminal region and first transmembrane domain of the alpha-subunit are required
      for modulation by auxiliary beta1-subunits, we examined whether beta1
      differentially modulates the N-terminal BK(Ca) alpha-subunit isoforms. In the
      absence of beta1, all isoforms had similar single-channel conductances and
      voltage-dependent activation. However, whereas beta1 did not modulate the voltage
      activation curve of MSSN, beta1 induced a significant leftward shift of the
      voltage activation curves of both the MDAL and MANG isoforms. These shifts, of
      which the MDAL was larger, occurred at both 10 MUM and 100 MUM Ca(2+). The beta1
      subunit increased the open dwell times of all three isoforms and decreased the
      closed dwell times of MANG and MDAL but increased the closed dwell times of MSSN.
      The distinct modulation of voltage activation by the beta1-subunit may be due to
      the differential effect of beta1 on burst duration and interburst intervals
      observed among these isoforms. Additionally, we observed that the related beta2
      subunit induced comparable leftward shifts in the voltage-activation curves of
      all three isoforms, indicating that the differential modulation of these isoforms
      was specific to beta1. These findings suggest that the relative expression of the
      N-terminal isoforms can fine-tune BK(Ca) channel activity in cells, highlighting
      a novel mechanism of BK(Ca) channel regulation.

PMID- 24569990
TI  - Inhibiting tyrosine phosphorylation of protein kinase Cdelta (PKCdelta) protects
      the salivary gland from radiation damage.
AB  - Radiation therapy for head and neck cancer can result in extensive damage to
      normal adjacent tissues such as the salivary gland and oral mucosa. We have shown
      previously that tyrosine phosphorylation at Tyr-64 and Tyr-155 activates PKCdelta
      in response to apoptotic stimuli by facilitating its nuclear import. Here we have
      identified the tyrosine kinases that mediate activation of PKCdelta in apoptotic
      cells and have explored the use of tyrosine kinase inhibitors for suppression of
      irradiation-induced apoptosis. We identify the damage-inducible kinase, c-Abl, as
      the PKCdelta Tyr-155 kinase and c-Src as the Tyr-64 kinase. Depletion of c-Abl or
      c-Src with shRNA decreased irradiation- and etoposide-induced apoptosis,
      suggesting that inhibitors of these kinases may be useful therapeutically.
      Pretreatment with dasatinib, a broad spectrum tyrosine kinase inhibitor, blocked
      phosphorylation of PKCdelta at both Tyr-64 and Tyr-155. Expression of "gate
      keeper" mutants of c-Abl or c-Src that are active in the presence of dasatinib
      restored phosphorylation of PKCdelta at Tyr-155 and Tyr-64, respectively.
      Imatinib, a c-Abl-selective inhibitor, also specifically blocked PKCdelta Tyr-155
      phosphorylation. Dasatinib and imatinib both blocked binding of PKCdelta to
      importin-alpha and nuclear import, demonstrating that tyrosine kinase inhibitors
      can inhibit nuclear accumulation of PKCdelta. Likewise, pretreatment with
      dasatinib also suppressed etoposide and radiation induced apoptosis in vitro. In
      vivo, pre-treatment of mice with dasatinib blocked radiation-induced apoptosis in
      the salivary gland by >60%. These data suggest that tyrosine kinase inhibitors
      may be useful prophylactically for protection of nontumor tissues in patients
      undergoing radiotherapy of the head and neck. 

PMID- 24569991
TI  - The efficacy of Raf kinase recruitment to the GTPase H-ras depends on H-ras
      membrane conformer-specific nanoclustering.
AB  - Solution structures and biochemical data have provided a wealth of mechanistic
      insight into Ras GTPases. However, information on how much the membrane
      organization of these lipid-modified proteins impacts on their signaling is still
      scarce. Ras proteins are organized into membrane nanoclusters, which are
      necessary for Ras-MAPK signaling. Using quantitative conventional and super
      resolution fluorescence methods, as well as mathematical modeling, we
      investigated nanoclustering of H-ras helix alpha4 and hypervariable region
      mutants that have different bona fide conformations on the membrane. By following
      the emergence of conformer-specific nanoclusters in the plasma membrane of
      mammalian cells, we found that conformers impart distinct nanoclustering
      responses depending on the cytoplasmic levels of the nanocluster scaffold
      galectin-1. Computational modeling revealed that complexes containing H-ras
      conformers and galectin-1 affect both the number and lifetime of nanoclusters and
      thus determine the specific Raf effector recruitment. Our results show that
      mutations in Ras can affect its nanoclustering response and thus allosterically
      effector recruitment and downstream signaling. We postulate that cancer- and
      developmental disease-linked mutations that are associated with the Ras membrane
      conformation may exhibit so far unrecognized Ras nanoclustering and therefore
      signaling alterations. 

PMID- 24569992
TI  - Stepwise organization of the beta-structure identifies key regions essential for
      the propagation and cytotoxicity of insulin amyloid fibrils.
AB  - Amyloid fibrils are supramolecular assemblies, the deposition of which is
      associated with many serious diseases including Alzheimer, prion, and Huntington
      diseases. Several smaller aggregates such as oligomers and protofibrils have been
      proposed to play a role in early stages of the fibrillation process; however,
      little is known about how these species contribute to the formation of mature
      amyloid fibrils with a rigid cross-beta structure. Here, we identified a new
      pathway for the formation of insulin amyloid fibrils at a high concentration of
      salt in which mature fibrils were formed in a stepwise manner via a prefibrillar
      intermediate: minute prefibrillar species initially accumulated, followed by the
      subsequent formation of thicker amyloid fibrils. Fourier transform infrared
      spectra suggested the sequential formation of two types of beta-sheets with
      different strength hydrogen bonds, one of which was developed concomitantly with
      the mutual assembly of the prefibrillar intermediate to form mature fibrils.
      Interestingly, fibril propagation and cellular toxicity appeared only after the
      later step of structural organization, and a comparison of beta-sheet regions
      between the prefibrillar intermediate and mature fibrils using proteolysis led to
      the proposal of specific regions essential for manifestation of these properties.

PMID- 24569993
TI  - Specific sorting and post-Golgi trafficking of dendritic potassium channels in
      living neurons.
AB  - Proper membrane localization of ion channels is essential for the function of
      neuronal cells. Particularly, the computational ability of dendrites depends on
      the localization of different ion channels in specific subcompartments. However,
      the molecular mechanisms that control ion channel localization in distinct
      dendritic subcompartments are largely unknown. Here, we developed a quantitative
      live cell imaging method to analyze protein sorting and post-Golgi vesicular
      trafficking. We focused on two dendritic voltage-gated potassium channels that
      exhibit distinct localizations: Kv2.1 in proximal dendrites and Kv4.2 in distal
      dendrites. Our results show that Kv2.1 and Kv4.2 channels are sorted into two
      distinct populations of vesicles at the Golgi apparatus. The targeting of Kv2.1
      and Kv4.2 vesicles occurred by distinct mechanisms as evidenced by their
      requirement for specific peptide motifs, cytoskeletal elements, and motor
      proteins. By live cell and super-resolution imaging, we identified a novel
      trafficking machinery important for the localization of Kv2.1 channels.
      Particularly, we identified non-muscle myosin II as an important factor in Kv2.1
      trafficking. These findings reveal that the sorting of ion channels at the Golgi
      apparatus and their subsequent trafficking by unique molecular mechanisms are
      crucial for their specific localizations within dendrites. 

PMID- 24569994
TI  - A novel mechanism by which tissue transglutaminase activates signaling events
      that promote cell survival.
AB  - Tissue transglutaminase (tTG) functions as a GTPase and an acyl transferase that
      catalyzes the formation of protein cross-links. tTG expression is frequently up
      regulated in human cancer, where it has been implicated in various aspects of
      cancer progression, including cell survival and chemo-resistance. However, the
      extent to which tTG cooperates with other proteins within the context of a cancer
      cell, versus its intrinsic ability to confer transformed characteristics to
      cells, is poorly understood. To address this question, we asked what effect the
      ectopic expression of tTG in a non-transformed cellular background would have on
      the behavior of the cells. Using NIH3T3 fibroblasts stably expressing a Myc
      tagged form of tTG, we found that tTG strongly protected these cells from serum
      starvation-induced apoptosis and triggered the activation of the PI3-kinase/mTOR
      Complex 1 (mTORC1)/p70 S6-kinase pathway. We determined that tTG forms a complex
      with the non-receptor tyrosine kinase c-Src and PI3-kinase, and that treating
      cells with inhibitors to block tTG function (monodansylcadaverine; MDC) or c-Src
      kinase activity (PP2) disrupted the formation of this complex, and prevented tTG
      from activating the PI3-kinase pathway. Moreover, treatment of fibroblasts over
      expressing tTG with PP2, or with inhibitors that inactivate components of the PI3
      kinase pathway, including PI3-kinase (LY294002) and mTORC1 (rapamycin), ablated
      the tTG-promoted survival of the cells. These findings demonstrate that tTG has
      an intrinsic capability to stimulate cell survival through a novel mechanism that
      activates PI3-kinase signaling events, thus highlighting tTG as a potential
      target for the treatment of human cancer. 

PMID- 24569996
TI  - Phosphoregulation of the ceramide transport protein CERT at serine 315 in the
      interaction with VAMP-associated protein (VAP) for inter-organelle trafficking of
      ceramide in mammalian cells.
AB  - The ceramide transport protein CERT mediates the inter-organelle transport of
      ceramide for the synthesis of sphingomyelin, presumably through endoplasmic
      reticulum (ER)-Golgi membrane contact sites. CERT has a short peptide motif named
      FFAT, which associates with the ER-resident membrane protein VAP. We show that
      the phosphorylation of CERT at serine 315, which is adjacent to the FFAT motif,
      markedly enhanced the interaction of CERT with VAP. The phosphomimetic CERT S315E
      mutant exhibited higher activity to support the ER-to-Golgi transport of ceramide
      than the wild-type control in a semi-intact cell system, and this enhanced
      activity was abrogated when its FFAT motif was deleted. The level of
      phosphorylation of CERT at Ser-315 increased in HeLa cells treated with a
      sphingolipid biosynthesis inhibitor or exogenous sphingomyelinase. Expression of
      CERT S315E induced intracellular punctate structures, to which CERT and VAP were
      co-localized, and the occurrence of the structure was dependent on both
      phosphatidylinositol 4-monophosphate binding and VAP binding activities of CERT.
      Phosphorylation of another region (named a serine-rich motif) in CERT is known to
      down-regulate the activity of CERT. Analysis of various CERT mutant constructs
      showed that the de-phosphorylation of the serine-rich motif and the
      phosphorylation of Ser-315 likely have the additive contribution to enhance the
      activity of CERT. These results demonstrate that the phosphorylation of CERT at
      the FFAT motif-adjacent serine affected its affinity for VAP, which may regulate
      the inter-organelle trafficking of ceramide in response to the perturbation of
      cellular sphingomyelin and/or other sphingolipids. 

PMID- 24569995
TI  - Bifunctional homodimeric triokinase/FMN cyclase: contribution of protein domains
      to the activities of the human enzyme and molecular dynamics simulation of domain
      movements.
AB  - Mammalian triokinase, which phosphorylates exogenous dihydroxyacetone and
      fructose-derived glyceraldehyde, is neither molecularly identified nor firmly
      associated to an encoding gene. Human FMN cyclase, which splits FAD and other
      ribonucleoside diphosphate-X compounds to ribonucleoside monophosphate and cyclic
      X-phosphodiester, is identical to a DAK-encoded dihydroxyacetone kinase. This
      bifunctional protein was identified as triokinase. It was modeled as a homodimer
      of two-domain (K and L) subunits. Active centers lie between K1 and L2 or K2 and
      L1: dihydroxyacetone binds K and ATP binds L in different subunits too distant (~
      14 A) for phosphoryl transfer. FAD docked to the ATP site with ribityl 4'-OH in a
      possible near-attack conformation for cyclase activity. Reciprocal inhibition
      between kinase and cyclase reactants confirmed substrate site locations. The
      differential roles of protein domains were supported by their individual
      expression: K was inactive, and L displayed cyclase but not kinase activity. The
      importance of domain mobility for the kinase activity of dimeric triokinase was
      highlighted by molecular dynamics simulations: ATP approached dihydroxyacetone at
      distances below 5 A in near-attack conformation. Based upon structure, docking,
      and molecular dynamics simulations, relevant residues were mutated to alanine,
      and kcat and Km were assayed whenever kinase and/or cyclase activity was
      conserved. The results supported the roles of Thr(112) (hydrogen bonding of ATP
      adenine to K in the closed active center), His(221) (covalent anchoring of
      dihydroxyacetone to K), Asp(401) and Asp(403) (metal coordination to L), and
      Asp(556) (hydrogen bonding of ATP or FAD ribose to L domain). Interestingly, the
      His(221) point mutant acted specifically as a cyclase without kinase activity.

PMID- 24569997
TI  - Characterization of Schizosaccharomyces pombe copper transporter proteins in
      meiotic and sporulating cells.
AB  - Meiosis requires copper to undertake its program in which haploid gametes are
      produced from diploid precursor cells. In Schizosaccharomyces pombe, copper is
      transported by three members of the copper transporter (Ctr) family, namely Ctr4,
      Ctr5, and Ctr6. Although central for sexual differentiation, very little is known
      about the expression profile, cellular localization, and physiological
      contribution of the Ctr proteins during meiosis. Analysis of gene expression of
      ctr4(+) and ctr5(+) revealed that they are primarily expressed in early meiosis
      under low copper conditions. In the case of ctr6(+), its expression is broader,
      being detected throughout the entire meiotic process with an increase during
      middle- and late-phase meiosis. Whereas the expression of ctr4(+) and ctr5(+) is
      exclusively dependent on the presence of Cuf1, ctr6(+) gene expression relies on
      two distinct regulators, Cuf1 and Mei4. Ctr4 and Ctr5 proteins co-localize at the
      plasma membrane shortly after meiotic induction, whereas Ctr6 is located on the
      membrane of vacuoles. After meiotic divisions, Ctr4 and Ctr5 disappear from the
      cell surface, whereas Ctr6 undergoes an intracellular re-location to co-localize
      with the forespore membrane. Under copper-limiting conditions, disruption of
      ctr4(+) and ctr6(+) results in altered SOD1 activity, whereas these mutant cells
      exhibit substantially decreased levels of CAO activity mostly in early- and
      middle-phase meiosis. Collectively, these results emphasize the notion that Ctr
      proteins exhibit differential expression, localization, and contribution in
      delivering copper to SOD1 and Cao1 proteins during meiosis. 

PMID- 24569999
TI  - Roles of the protruding loop of factor B essential for the localization of
      lipoproteins (LolB) in the anchoring of bacterial triacylated proteins to the
      outer membrane.
AB  - The Lol system comprising five Lol proteins, LolA through LolE, sorts Escherichia
      coli lipoproteins to outer membranes. The LolCDE complex, an ATP binding cassette
      transporter in inner membranes, releases outer membrane-specific lipoproteins in
      an ATP-dependent manner, causing formation of the LolA-lipoprotein complex in the
      periplasm. LolA transports lipoproteins through the periplasm to LolB on outer
      membranes. LolB is itself a lipoprotein anchored to outer membranes, although the
      membrane anchor is functionally dispensable. LolB then localizes lipoproteins to
      outer membranes through largely unknown mechanisms. The crystal structure of LolB
      is similar to that of LolA, and it possesses a hydrophobic cavity that
      accommodates acyl chains of lipoproteins. To elucidate the molecular function of
      LolB, a periplasmic version of LolB, mLolB, was mutagenized at various conserved
      residues. Despite the lack of acyl chains, most defective mutants were insoluble.
      However, a derivative with glutamate in place of leucine 68 was soluble and
      unable to localize lipoproteins to outer membranes. This leucine is present in a
      loop protruding from mLolB into an aqueous environment, and no analogous loop is
      present in LolA. Thus, leucine 68 was replaced with other residues. Replacement
      by acidic, but not hydrophobic, residues generated for the first time mLolB
      derivatives that can accept but cannot localize lipoproteins to outer membranes.
      Moreover, deletion of the leucine with neighboring residues impaired the
      lipoprotein receptor activity. Based on these observations, the roles of the
      protruding loop of LolB in the last step of lipoprotein sorting are discussed. 

PMID- 24569998
TI  - Furanocoumarins are a novel class of modulators for the transient receptor
      potential vanilloid type 1 (TRPV1) channel.
AB  - Furanocoumarin imperatorin is the major active component of Angelica dahurica
      root extracts, widely used in traditional medicine to treat headache, toothache,
      and orbital eye pain. In this study, we investigated the mechanisms that may
      underlie the pain-relieving effects of the compound. We found that imperatorin
      significantly inhibited formalin- and capsaicin-induced nocifensive responses but
      did not alter baseline thermal withdrawal thresholds in the rat. We established
      that imperatorin is a weak agonist of TRPV1, a channel implicated in detecting
      several noxious stimuli, exhibiting a 50% effective concentration (EC50) of 12.6
      +/- 3.2 MUM. A specific TRPV1 antagonist, JNJ-17203212 (0.5 MUM), potently
      inhibited imperatorin-induced TRPV1 activation. Site-directed mutagenesis studies
      revealed that imperatorin most likely acted via a site adjacent to or overlapping
      with the TRPV1 capsaicin-binding site. TRPV1 recovery from desensitization was
      delayed in the presence of imperatorin. Conversely, imperatorin sensitized TRPV1
      to acid activation but did not affect the current amplitude and/or the activation
      inactivation properties of Na(v)1.7, a channel important for transmission of
      nociceptive information. Thus, our data indicate that furanocoumarins represent a
      novel group of TRPV1 modulators that may become important lead compounds in the
      drug discovery process aimed at developing new treatments for pain management.

PMID- 24570000
TI  - Neuroendocrine signaling via the serotonin transporter regulates clearance of
      apoptotic cells.
AB  - Serotonin (5-hydroxytryptamine; 5-HT) is a CNS neurotransmitter increasingly
      recognized to exert immunomodulatory effects outside the CNS that contribute to
      the pathogenesis of autoimmune and chronic inflammatory diseases. 5-HT signals to
      activate the RhoA/Rho kinase (ROCK) pathway, a pathway known for its ability to
      regulate phagocytosis. The clearance of apoptotic cells (i.e. efferocytosis) is a
      key modulator of the immune response that is inhibited by the RhoA/ROCK pathway.
      Because efferocytosis is defective in many of the same illnesses where 5-HT has
      been implicated in disease pathogenesis, we hypothesized that 5-HT would suppress
      efferocytosis via activation of RhoA/ROCK. The effect of 5-HT on efferocytosis
      was examined in murine peritoneal and human alveolar macrophages, and its
      mechanisms were investigated using pharmacologic blockade and genetic deletion. 5
      HT impaired efferocytosis by murine peritoneal macrophages and human alveolar
      macrophages. 5-HT increased phosphorylation of myosin phosphatase subunit 1 (Mypt
      1), a known ROCK target, and inhibitors of RhoA and ROCK reversed the suppressive
      effect of 5-HT on efferocytosis. Peritoneal macrophages expressed the 5-HT
      transporter and 5-HT receptors (R) 2a, 2b, but not 2c. Inhibition of 5-HTR2a and
      5-HTR2b had no effect on efferocytosis, but blockade of the 5-HT transporter
      prevented 5-HT-impaired efferocytosis. Genetic deletion of the 5-HT transporter
      inhibited 5-HT uptake into peritoneal macrophages, prevented 5-HT-induced
      phosphorylation of Mypt-1, reversed the inhibitory effect of 5-HT on
      efferocytosis, and decreased cellular peritoneal inflammation. These results
      suggest a novel mechanism by which 5-HT might disrupt efferocytosis and
      contribute to the pathogenesis of autoimmune and chronic inflammatory diseases. 

PMID- 24570001
TI  - Distinct effects of the mesenchymal dysplasia gene variant of murine Patched-1
      protein on canonical and non-canonical Hedgehog signaling pathways.
AB  - Hedgehog (Hh) signaling requires regulation of the receptor Patched-1 (Ptch1),
      which, in turn, regulates Smoothened activity (canonical Hh signaling) as well as
      other non-canonical signaling pathways. The mutant Ptch1 allele mesenchymal
      dysplasia (mes), which truncates the Ptch1 C terminus, produces a limited
      spectrum of developmental defects in mice as well as deregulation of canonical Hh
      signaling in some, but not all, affected tissues. Paradoxically, mes suppresses
      canonical Hh signaling and binds to Hh ligands with an affinity similar to wild
      type mouse Ptch1 (mPtch1). We characterized the distinct activities of the mes
      variant of mPtch1 mediating Hh signaling through both canonical and non-canonical
      pathways. We demonstrated that mPtch1 bound c-src in an Hh-regulated manner.
      Stimulation with Sonic Hedgehog (Shh) of primary mammary mesenchymal cells from
      wild-type and mes animals activated Erk1/2. Although Shh activated c-src in wild
      type cells, c-src was constitutively activated in mes mesenchymal cells.
      Transient assays showed that wild-type mPtch1, mes, or mPtch1 lacking the C
      terminus repressed Hh signaling in Ptch1-deficient mouse embryo fibroblasts and
      that repression was reversed by Shh, revealing that the C terminus was
      dispensable for mPtch1-dependent regulation of canonical Hh signaling. In
      contrast to these transient assays, constitutively high levels of mGli1 but not
      mPtch1 were present in primary mammary mesenchymal cells from mes mice, whereas
      the expression of mPtch1 was similarly induced in both mes and wild-type cells.
      These data define a novel signal transduction pathway involving c-src that is
      activated by the Hh ligands and reveals the requirement for the C terminus of
      Ptch in regulation of canonical and non-canonical Hh signaling pathways. 

PMID- 24570003
TI  - Discovery of PI-1840, a novel noncovalent and rapidly reversible proteasome
      inhibitor with anti-tumor activity.
AB  - The proteasome inhibitor bortezomib is effective in hematologic malignancies such
      as multiple myeloma but has little activity against solid tumors, acts
      covalently, and is associated with undesired side effects. Therefore, noncovalent
      inhibitors that are less toxic and more effective against solid tumors are
      desirable. Structure activity relationship studies led to the discovery of PI
      1840, a potent and selective inhibitor for chymotrypsin-like (CT-L) (IC50 value =
      27 +/- 0.14 nm) over trypsin-like and peptidylglutamyl peptide hydrolyzing (IC50
      values >100 MUm) activities of the proteasome. Furthermore, PI-1840 is over 100
      fold more selective for the constitutive proteasome over the immunoproteasome.
      Mass spectrometry and dialysis studies demonstrate that PI-1840 is a noncovalent
      and rapidly reversible CT-L inhibitor. In intact cancer cells, PI-1840 inhibits
      CT-L activity, induces the accumulation of proteasome substrates p27, Bax, and
      IkappaB-alpha, inhibits survival pathways and viability, and induces apoptosis.
      Furthermore, PI-1840 sensitizes human cancer cells to the mdm2/p53 disruptor,
      nutlin, and to the pan-Bcl-2 antagonist BH3-M6. Finally, in vivo, PI-1840 but not
      bortezomib suppresses the growth in nude mice of human breast tumor xenografts.
      These results warrant further evaluation of a noncovalent and rapidly reversible
      proteasome inhibitor as potential anticancer agents against solid tumors. 

PMID- 24570002
TI  - Regulation of large conductance Ca2+-activated K+ (BK) channel beta1 subunit
      expression by muscle RING finger protein 1 in diabetic vessels.
AB  - The large conductance Ca(2+)-activated K(+) (BK) channel, expressed abundantly in
      vascular smooth muscle cells (SMCs), is a key determinant of vascular tone. BK
      channel activity is tightly regulated by its accessory beta1 subunit (BK-beta1).
      However, BK channel function is impaired in diabetic vessels by increased
      ubiquitin/proteasome-dependent BK-beta1 protein degradation. Muscle RING finger
      protein 1 (MuRF1), a muscle-specific ubiquitin ligase, is implicated in many
      cardiac and skeletal muscle diseases. However, the role of MuRF1 in the
      regulation of vascular BK channel and coronary function has not been examined. In
      this study, we hypothesized that MuRF1 participated in BK-beta1 proteolysis,
      leading to the down-regulation of BK channel activation and impaired coronary
      function in diabetes. Combining patch clamp and molecular biological approaches,
      we found that MuRF1 expression was enhanced, accompanied by reduced BK-beta1
      expression, in high glucose-cultured human coronary SMCs and in diabetic vessels.
      Knockdown of MuRF1 by siRNA in cultured human SMCs attenuated BK-beta1
      ubiquitination and increased BK-beta1 expression, whereas adenoviral expression
      of MuRF1 in mouse coronary arteries reduced BK-beta1 expression and diminished BK
      channel-mediated vasodilation. Physical interaction between the N terminus of BK
      beta1 and the coiled-coil domain of MuRF1 was demonstrated by pulldown assay.
      Moreover, MuRF1 expression was regulated by NF-kappaB. Most importantly,
      pharmacological inhibition of proteasome and NF-kappaB activities preserved BK
      beta1 expression and BK-channel-mediated coronary vasodilation in diabetic mice.
      Hence, our results provide the first evidence that the up-regulation of NF-kappaB
      dependent MuRF1 expression is a novel mechanism that leads to BK channelopathy
      and vasculopathy in diabetes. 

PMID- 24570004
TI  - Developmental regulation of synthesis and dimerization of the amyloidogenic
      protease inhibitor cystatin C in the hematopoietic system.
AB  - The cysteine protease inhibitor cystatin C is thought to be secreted by most
      cells and eliminated in the kidneys, so its concentration in plasma is diagnostic
      of kidney function. Low extracellular cystatin C is linked to pathologic protease
      activity in cancer, arthritis, atherosclerosis, aortic aneurism, and emphysema.
      Cystatin C forms non-inhibitory dimers and aggregates by a mechanism known as
      domain swapping, a property that reportedly protects against Alzheimer disease
      but can also cause amyloid angiopathy. Despite these clinical associations,
      little is known about the regulation of cystatin C production, dimerization, and
      secretion. We show that hematopoietic cells are major contributors to
      extracellular cystatin C levels in healthy mice. Among these cells, macrophages
      and dendritic cells (DC) are the predominant producers of cystatin C. Both cell
      types synthesize monomeric and dimeric cystatin C in vivo, but only secrete
      monomer. Dimerization occurs co-translationally in the endoplasmic reticulum and
      is regulated by the levels of reactive oxygen species (ROS) derived from
      mitochondria. Drugs or stimuli that reduce the intracellular concentration of ROS
      inhibit cystatin C dimerization. The extracellular concentration of inhibitory
      cystatin C is thus partly dependent on the abundance of macrophages and DC, and
      the ROS levels. These results have implications for the diagnostic use of serum
      cystatin C as a marker of kidney function during inflammatory processes that
      induce changes in DC or macrophage abundance. They also suggest an important role
      for macrophages, DC, and ROS in diseases associated with the protease inhibitory
      activity or amyloidogenic properties of cystatin C. 

PMID- 24570005
TI  - The plasma membrane calcium pump: new ways to look at an old enzyme.
AB  - The three-dimensional structure of the PMCA pump has not been solved, but its
      basic mechanistic properties are known to repeat those of the other Ca(2+) pumps.
      However, the pump also has unique properties. They concern essentially its
      numerous regulatory mechanisms, the most important of which is the autoinhibition
      by its C-terminal tail. Other regulatory mechanisms involve protein kinases and
      the phospholipids of the membrane in which the pump is embedded. Permanent
      activation of the pump, e.g. by calmodulin, is physiologically as harmful to
      cells as its absence. The concept is now emerging that the global control of cell
      Ca(2+) may not be the main function of the pump; in some cell types, it could
      even be irrelevant. The main pump role would be the regulation of Ca(2+) in cell
      microdomains in which the pump co-segregates with partners that modulate the
      Ca(2+) message and transduce it to important cell functions. 

PMID- 24570008
TI  - (31)P magnetic resonance spectroscopy of the breast and the influence of the
      menstrual cycle.
AB  - Phosphorus metabolite ratios are potential biomarkers in breast cancer diagnosis
      and treatment monitoring. Our purpose was to investigate the metabolite ratios
      phosphomonoester to phosphodiester, phosphoethanolamine (PE) to
      glycerophosphoethanolamine (GPE), and phosphocholine (PC) to
      glycerophosphocholine (GPC) in glandular breast tissue, and the potential effect
      of the menstrual cycle, using (31)P magnetic resonance spectroscopy (MRS) at 7T.
      Seven women with regular menstrual cycles each underwent four examinations using
      a 3D (31)P multi-echo magnetic resonance spectroscopic imaging sequence. Peak
      integrals were assessed using IDL and JMRUI software. First, T2 relaxation times
      were calculated using multi-echo data pooled across subjects and time points.
      Subsequent, metabolite ratios were calculated for each phase of the menstrual
      cycle using the calculated T2 values to account for when combining the free
      induction decay and all five echoes. The metabolite ratios were calculated both
      on group level and individually. T2 decay fits resulted in a T2 relaxation time
      for PE of 154 ms (95 % CI 144-164), for PC of 173 ms (95 % CI 148-205), for Pi of
      188 ms (95 % CI 182-193), for GPE of 48 ms (95 % CI 44-53), and for GPC of 23 ms
      (95 % CI 21-26). The metabolite ratios analyzed on group level showed negligible
      variation throughout the menstrual cycle. Individual results did show an apparent
      intra-individual variation; however, not significant due to the measurements'
      uncertainty. To conclude, phospholipids in glandular tissue as measured with
      (31)P MRS at 7 T are not significantly affected by the menstrual cycle.

PMID- 24570007
TI  - DNA promoter methylation-dependent transcription of the double C2-like domain
      beta (DOC2B) gene regulates tumor growth in human cervical cancer.
AB  - Double C2-like domain beta (DOC2B) gene encodes for a calcium-binding protein,
      which is involved in neurotransmitter release, sorting, and exocytosis. We have
      identified the promoter region of the DOC2B gene as hypermethylated in pre
      malignant, malignant cervical tissues, and cervical cancer cell lines by
      methylation-sensitive dimethyl sulfoxide-polymerase chain reaction and bisulfite
      genome sequencing; whereas, it was unmethylated in normal cervical tissues (p <
      0.05). The promoter hypermethylation was inversely associated with mRNA
      expression in SiHa, CaSki, and HeLa cells and treatment with demethylating agent
      5-aza-2-deoxycytidine restored DOC2B expression. The region -630 to +25 bp of the
      DOC2B gene showed robust promoter activity by a luciferase reporter assay and was
      inhibited by in vitro artificial methylation with Sss1 methylase prior to
      transient transfections. Overexpression of the DOC2B gene in SiHa cells when
      compared with controls showed significantly reduced colony formation, cell
      proliferation, induced cell cycle arrest, and repressed cell migration and
      invasion (p < 0.05). Ectopic expression of DOC2B resulted in anoikis-mediated
      cell death and repressed tumor growth in a nude mice xenograft model (p < 0.05).
      DOC2B expressing cells showed a significant increase in intracellular calcium
      level (p < 0.05), impaired AKT1 and ERK1/2 signaling, and induced actin
      cytoskeleton remodeling. Our results show that promoter hypermethylation and
      silencing of the DOC2B gene is an early and frequent event during cervical
      carcinogenesis and whose reduced expression due to DNA promoter methylation may
      lead to selective cervical tumor growth. 

PMID- 24570006
TI  - Structural and biochemical analyses of glycoside hydrolase family 26 beta
      mannanase from a symbiotic protist of the termite Reticulitermes speratus.
AB  - Termites and their symbiotic protists have established a prominent dual
      lignocellulolytic system, which can be applied to the biorefinery process. One of
      the major components of lignocellulose from conifers is glucomannan, which
      comprises a heterogeneous combination of beta-1,4-linked mannose and glucose.
      Mannanases are known to hydrolyze the internal linkage of the glucomannan
      backbone, but the specific mechanism by which they recognize and accommodate
      heteropolysaccharides is currently unclear. Here, we report biochemical and
      structural analyses of glycoside hydrolase family 26 mannanase C (RsMan26C) from
      a symbiotic protist of the termite Reticulitermes speratus. RsMan26C was
      characterized based on its catalytic efficiency toward glucomannan, compared with
      pure mannan. The crystal structure of RsMan26C complexed with gluco-manno
      oligosaccharide(s) explained its specificities for glucose and mannose at
      subsites -5 and -2, respectively, in addition to accommodation of both glucose
      and mannose at subsites -3 and -4. RsMan26C has a long open cleft with a
      hydrophobic platform of Trp(94) at subsite -5, facilitating enzyme binding to
      polysaccharides. Notably, a unique oxidized Met(85) specifically interacts with
      the equatorial O-2 of glucose at subsite -3. Our results collectively indicate
      that specific recognition and accommodation of glucose at the distal negative
      subsites confers efficient degradation of the heteropolysaccharide by mannanase. 

PMID- 24570010
TI  - Technique of per-oral endoscopic myotomy (POEM) of the esophagus (with video).
AB  - BACKGROUND: Per-Oral Endoscopic Myotomy (POEM) is becoming an acceptable
      alternative to laparoscopic cardiomyotomy for esophageal motility disorders. The
      aim of this video is to provide key technical steps to completing this procedure.
      METHOD: Each patient underwent diagnostic investigations including high
      resolution manometry (HRM), esophageogastroduodenoscopy (EGD), and timed-barium
      swallow for primary esophageal motility disorders preoperatively. Patients
      undergoing POEM procedures are preoperatively prepared by taking Nystatin swish
      and-swallow for 3 days, 24 h of clear liquid diet, and 12 h of NPO. Preoperative
      antibiotics are given. Under general anesthesia and with the patient in the
      supine position, endoscopy with CO2 insufflation is prepared. Special endoscopic
      instruments and electrocautery settings are required to perform the POEM
      procedure, as illustrated in the slides. POEM is performed in six key/critical
      steps: (1) diagnostic endoscopy; (2) taking measurements; (3) esophageal
      mucosotomy creation; (4) submucosal tunneling; (5) selective circular myotomy of
      the anterior lower esophageal sphincter; and (6) closure of the mucosotomy.
      According to our protocol, all patients get an esophogram the next morning after
      surgery prior to discharge. The patient receives objective testing (HRM with 24
      PH Impedance test, EGD, and timed-barium swallow) 6 months postoperatively.
      CONCLUSION: In six key steps, POEM can be accomplished as described in the video.

PMID- 24570009
TI  - Portomesenteric vein thrombosis after laparoscopic sleeve gastrectomy.
AB  - INTRODUCTION: Portal and mesenteric vein thrombosis are relatively uncommon
      surgical complications, with difficult diagnosis and potentially severe
      consequences due to higher risk of bowel infarction. The purpose of this study
      was to present a series of patients who developed postoperative portal vein
      thrombosis after laparoscopic sleeve gastrectomy. METHODS: This is a
      retrospective analysis of patients who underwent sleeve gastrectomy between June
      2005 and June 2011 who developed portal vein thrombosis. Demographic data,
      personal risk factors, family history of thrombosis, and postoperative results of
      thrombophilia study were analyzed in this study. RESULTS: A total of 1,713
      laparoscopic sleeve gastrectomies were performed. Seventeen patients (1 %)
      developed portal vein thrombosis after surgery. Of the 17 patients, 16 were
      women, 8 had a history of smoking, 7 used oral contraceptives, and 2 had a family
      history of deep vein thrombosis of the lower limbs. All patients were discharged
      on the third day of surgery with no immediate complications. Symptoms presented
      at a median of 15 (range, 8-43) days after surgery with abdominal pain in most
      cases. One case required emergency laparotomy and splenectomy because of an
      active bleeding hematoma with massive portomesenteric vein thrombosis. In 11
      cases, a thrombosis of the main portal vein was identified, in 15 the right
      portal branch was compromised, and in 10 the left portal branch. Eleven patients
      presented thrombosis of the superior mesenteric vein, and ten patients presented
      a concomitant thrombosis of the splenic vein. A massive PMVT was presented in six
      cases. Seven patients had a positive thrombophilia study. CONCLUSIONS: Portal
      vein thrombosis and/or mesenteric thrombosis are relatively uncommon
      complications in patients undergoing bariatric surgery. In this series, the
      portomesenteric vein thrombosis was the most common complication after LSG in a
      high-volume center.

PMID- 24570011
TI  - Electrostatic precipitation is a novel way of maintaining visual field clarity
      during laparoscopic surgery: a prospective double-blind randomized controlled
      pilot study.
AB  - BACKGROUND: UltravisionTM is a new device that utilizes electrostatic
      precipitation to clear surgical smoke. The aim was to evaluate its performance
      during laparoscopic cholecystectomy. METHODS: Patients undergoing laparoscopic
      cholecystectomy were randomized into "active (device on)" or "control (device
      off)." Three operating surgeons scored the percentage effective visibility and
      three reviewers scored the percentage of the procedure where smoke was present.
      All assessors also used a 5-point scale (1 = imperceptible/excellent and 5 = very
      annoying/bad) to rate visual impairment. Secondary outcomes were the number of
      smoke-related pauses, camera cleaning, and pneumoperitoneum reductions. Mean
      results are presented with 95% confidence intervals (CI). RESULTS: In 30 patients
      (active 13, control 17), the effective visibility was 89.2% (83.3-95.0) for
      active cases and 71.2% (65.7-76.7) for controls. The proportion of the procedure
      where smoke was present was 41.1% (33.8-48.3) for active cases and 61.5% (49.0
      74.1) for controls. Operating surgeons rated the visual impairment as 2.2 (1.7
      2.6) for active cases and 3.2 (2.8-3.5) for controls. Reviewers rated the visual
      impairment as 2.3 (2.0-2.5) for active cases and 3.2 (2.8-3.7) for controls. In
      the active group, 23% of procedures were paused to allow smoke clearance compared
      to 94% of control cases. Camera cleaning was not needed in 85% of active
      procedures and 35% of controls. The pneumoperitoneum was reduced in 0% of active
      cases and 88% of controls. CONCLUSIONS: UltravisionTM improves visibility during
      laparoscopic surgery and reduces delays in surgery for smoke clearance and camera
      cleaning.

PMID- 24570012
TI  - Ultrasound-guided double-tract percutaneous cholecystostomy combined with a
      choledochoscope for performing cholecystolithotomies in high-risk surgical
      patients.
AB  - BACKGROUND: Cholecystolithiasis is the most common disease treated by general
      surgery, with an incidence of about 0.15-0.22%. The most common therapies are
      open cholecystectomy (OC) or laparoscopic cholecystectomy (LC). However, with a
      greater understanding of the function of the cholecyst, more and more patients
      and surgeons are aware that preserving the functional cholecyst is important for
      young patients, as well as patients who would not tolerate anesthesia associated
      with either OC or LC. Based on these considerations, we have introduced a
      notable, minimally invasive treatment for cholecystolithotomy. METHODS: We
      performed a retrospective review of patients with cholecystolithiasis who were
      unable to tolerate surgery or who insisted on preserving the functional
      cholecyst. Our particular approach can be simply described as ultrasound-guided
      percutaneous cholecystostomy combined with a choledochoscope for performing a
      cholecystolithotomy under local anesthesia. RESULTS: Ten patients with
      cholecystolithiasis were treated via this approach. All except one patient had
      their gallbladder stones totally removed under local anesthesia, without the
      aggressive procedures associated with OC or LC. The maximum number of gallbladder
      stones removed was 16, and the maximum diameter was 13 mm without lithotripsy.
      After the minimally invasive surgery, the cholecyst contractile functions of all
      patients were normal, confirmed via ultrasound after a high-fat diet.
      Complications such as bile duct injury, biliary fistula, and bleeding occurred
      significantly less often than with OC and LC. The recurrence rates for each of 2
      post-operative years were about 11.11% (1/9, excluding a failure case) with
      uncertainty surrounding recurrence or residue, and 22.22% (2/9, including one non
      recurrence patient with follow-up time of 22 months), respectively. CONCLUSIONS:
      Ultrasound-guided percutaneous cholecystostomy combined with choledochoscope is a
      safe, efficient, and minimally invasive cholecystolithotomy method. We recommend
      this technique for the management of small stones (less than 15 mm) in high-risk
      surgical patients.

PMID- 24570013
TI  - Neuroanatomical correlates of laparoscopic surgery training.
AB  - BACKGROUND: Better understanding of the brain regions involved in performing
      laparoscopic surgery is likely to provide important insights for improving
      laparoscopic training and assessment in the future. To our knowledge, this is the
      first study using real Fundamentals of Laparoscopy Training (FLS)-based
      laparoscopic surgery training tasks in the functional magnetic resonance imaging
      (fMRI) environment to provide extensive characterization of the brain regions
      involved in this specific task execution. METHODS: Nine right-handed subjects
      practiced five FLS-modified laparoscopic surgery-training tasks with a training
      box for ten sessions in a simulated fMRI environment. Following the last practice
      session, they underwent 3 T fMRI while performing each task. RESULTS: An increase
      in the extent of brain activation was observed as the complexity of the tasks
      increased. Activation in the precentral gyrus, postcentral gyrus, and premotor
      regions was observed in the performance of all tasks, whereas the superior
      parietal lobe (SPL) was activated in the more complex tasks. The mean score and
      brain activation for performance with the dominant hand were larger than those
      observed during performance with the non-dominant hand. CONCLUSIONS: Performing
      more complex tasks requires higher visual spatial ability and motor planning.
      Given the need for ambidextrous skills during laparoscopic tasks, the finding
      that lower scores and smaller brain recruitment occurred in executing tasks with
      the non-dominant hand than with the dominant hand suggests designing future
      training tasks to train the non-dominant hand more effectively. This may serve to
      improve overall performance in bi-manual tasks. Studies of this kind may
      facilitate the evidence-based development of strategies to improve the quality of
      laparoscopy training and assessment.

PMID- 24570014
TI  - Clinical outcomes of second-look endoscopy after gastric endoscopic submucosal
      dissection: predictive factors with high risks of bleeding.
AB  - BACKGROUND: A second-look endoscopy is routinely performed after endoscopic
      submucosal dissection (ESD) in many institutions, although the need is
      questionable. Additional hemostatic procedures might be necessary for the post
      ESD ulcer with a high risk of bleeding. We investigated the predictive factors
      for post-ESD ulcers with a high risk of bleeding. METHODS: Second-look endoscopy
      was performed on the day following ESD. The post-ESD ulcers were categorized into
      two risk groups according to the Forrest classification: high-risk ulcer stigma
      (type I and IIa) and low-risk ulcer stigma. We analyzed the risk factors
      associated with high-risk ulcer stigma and late delayed bleeding. RESULTS: During
      the study period, 616 ESD procedures were performed. Second-look endoscopy
      revealed that the incidence of high-risk ulcer stigma post-ESD was 15.1%. Early
      and late delayed bleeding rates were 3.7 and 1.9%, respectively. Multivariate
      analysis revealed that submucosal fibrosis and nausea were significantly related
      to high-risk ulcer stigma after ESD. Multivariate analysis revealed that surface
      erosion, location of the lesion, and high-risk ulcer stigma identified by second
      look endoscopy were significantly associated with late delayed bleeding.
      CONCLUSIONS: The effective use of selective second-look endoscopy will help limit
      unnecessary procedures. Submucosal fibrosis and nausea were risk factors
      associated with high-risk ulcer stigma after ESD.

PMID- 24570015
TI  - The efficacy of single-dose postoperative intravenous dexamethasone for pain
      relief after endoscopic submucosal dissection for gastric neoplasm.
AB  - BACKGROUND: Endoscopic submucosal dissection (ESD) is the gold standard technique
      for en bloc resection of large superficial tumors in the upper and lower
      gastrointestinal tract. Little is known about the management of epigastric pain
      after ESD of gastric neoplasms. This study investigated the utility and safety of
      single-dose, perioperative, intravenous dexamethasone for epigastric pain relief
      following ESD. METHODS: The efficacy of intravenous dexamethasone 0.15 mg/kg
      (DEXA group) compared with saline-only placebo (placebo) for epigastric pain
      after ESD of early gastric neoplasms was assessed in a double-blinded, placebo
      controlled trial. Patients completed a questionnaire about present pain intensity
      (PPI) and short-form McGill pain (SF-MP) categories for immediate and 6-, 12-,
      and 24-h postoperative periods. The primary outcome variable was PPI at 6 h
      following ESD. Secondary outcome variables included pain medication, SF-MP
      scores, complications, second-look endoscopic findings, and length of stay.
      RESULTS: A total of 36 patients participated in the study. The mean 6-h PPI value
      was lower (p < 0.001) in the DEXA group (1.61 +/- 0.21) than in the placebo group
      (2.66 +/- 0.19). The total 6-h SF-MP score, especially the sensory domain, was
      higher (p = 0.054) in the placebo group (11.56 +/- 0.75) than in the DEXA group
      (8.89 +/- 0.75). Tramadol for epigastric pain relief was more frequent (p =
      0.026) in the placebo group (44.4%) than in the DEXA group (11.1%). No
      differences were noted between groups in length of stay or complications,
      including acute or delayed bleeding. The distribution of artificial ulcer
      patterns at 48-h post-ESD as determined by second-look endoscopy was similar in
      both groups. CONCLUSION: Single-dose perioperative intravenous dexamethasone
      after ESD effectively relieved epigastric pain 6 h postoperatively.

PMID- 24570016
TI  - Surgical smoke may be a biohazard to surgeons performing laparoscopic surgery.
AB  - BACKGROUND: Surgical smoke production is inevitable during surgical procedures.
      Although many workplaces have adopted smoke-free environments, healthcare
      workers, especially surgeons, continue to be exposed to surgical smoke. METHODS:
      From February 2013 to March 2013, a total of 20 patients underwent
      transperitoneal laparoscopic nephrectomy for renal cell carcinoma. A 5-L gas
      sample was collected 30 min after the electrocautery device was first used and
      was analyzed by gas chromatography and mass spectrometry. Cancer risk was
      calculated for carcinogenic compounds and hazard quotient was calculated for
      noncarcinogenic compounds using US Environmental Protection Agency guidelines.
      RESULTS: Twenty patients with a median age of 57.5 years were enrolled in the
      study. Eighteen volatile organic compounds were detected by Japanese indoor air
      standards mix analysis. The cancer risks were ethanol, 5.10 * 10(-5) +/- 6.35 *
      10(-5); 1,2-dichloroethane, 4.75 * 10(-3) +/- 7.42 * 10(-4); benzene, 1.09 * 10(
      3) +/- 4.33 * 10(-4); ethylbenzene, 2.87 * 10(-5) +/- 1.32 * 10(-5); and styrene,
      2.94 * 10(-6) +/- 1.16 * 10(-6). The hazard quotients were acetone, 1.88 * 10(-2)
      +/- 7.63 * 10(-3); hexane, 1.48 * 10(-1) +/- 8.70 * 10(-2); benzene, 4.66 +/-
      1.85; toluene, 2.61 * 10(-2) +/- 7.23 * 10(-3); p-xylene, 1.81 * 10(-1) +/- 6.45
      * 10(-2); o-xylene, 2.40 * 10(-2) +/- 3.33 * 10(-2); and styrene, 5.15 * 10(-3)
      +/- 2.03 * 10(-3). CONCLUSIONS: For five carcinogenic compounds detected, the
      cancer risk was greater than negligible. For 1,2-dichloroethane and benzene, the
      risk was classified as unacceptable. Analysis of noncarcinogenic compounds showed
      that risk reduction measures are needed for benzene. Even though surgical smoke
      is not an immediate health hazard, operating room personnel should be aware of
      the potential long-term health risks associated with exposure.

PMID- 24570017
TI  - Where should a school shoe provide flexibility and support for the asymptomatic 6
      to 10-year-olds and on what information is this based? A Delphi yielded
      consensus.
AB  - BACKGROUND: There is a paucity of evidence regarding the design of children's
      footwear in relation to musculoskeletal structure. OBJECTIVES: The aim was to
      gain consensus regarding where flexibility and support should be given on a
      school shoe for the 6- to 10-year-olds. STUDY DESIGN: Delphi Questionnaire.
      METHODS: Recruitment of 10 Allied Health Professionals yielded a consensus group.
      Those recruited had dedicated experience in paediatrics and foot health. Rounds
      of questions were delivered to investigate the basis of the opinions made by the
      group on the location of support and flexibility in a school shoe for the age
      range identified. RESULTS: Six themes were generated. Four themes gained 100%
      consensus regarding footwear allowing normal foot movement, footwear allowing
      normal forefoot function, footwear providing a stable base and the foot being
      secure in the shoe. Fleiss' kappa calculations revealed 'poor agreement' for the
      remaining two themes regarding clinical intervention and the purpose of footwear
      design in the midfoot in both the upper and sole of the shoe. CONCLUSION: The
      qualitative data generated through discussion have highlighted areas where more
      understanding and research are required, particularly in understanding how, in
      the long term, shoe design can affect the developing foot. CLINICAL RELEVANCE:
      Children's footwear advice is often delivered from experience and personal
      belief. This article questions current understanding and opinion from clinical
      experts in the field of paediatric footwear and highlights that there is a lack
      of knowledge and confidence into the effects of children's footwear. There is a
      strong requirement for further empirical research to be completed on children's
      footwear to allow clinicians to formulate relevant and appropriate footwear
      advice.

PMID- 24570019
TI  - Golf hand prosthesis performance of transradial amputees.
AB  - BACKGROUND: Typical upper limb prostheses may limit sports participation;
      therefore, specialized terminal devices are often needed. The purpose of this
      study was to evaluate the ability of transradial amputees to play golf using a
      specialized terminal device. CASE DESCRIPTION AND METHODS: Club head speed, X
      factor, and elbow motion of two individuals with transradial amputations using an
      Eagle Golf terminal device were compared to a non-amputee during a golf swing.
      Measurements were collected pre/post training with various stances and grips.
      FINDINGS AND OUTCOMES: Both prosthesis users preferred a right-handed stance
      initially; however, after training, one preferred a left-handed stance. The
      amputees had slower club head speeds and a lower X-factor compared to the non
      amputee golfer, but increased their individual elbow motion on the prosthetic
      side after training. CONCLUSION: Amputees enjoyed using the device, and it may
      provide kinematic benefits indicated by the increase in elbow flexion on the
      prosthetic side. CLINICAL RELEVANCE: The transradial amputees were able to swing
      a golf club with sufficient repetition, form, and velocity to play golf
      recreationally. Increased elbow flexion on the prosthetic side suggests a
      potential benefit from using the Eagle Golf terminal device. Participating in
      recreational sports can increase amputees' health and quality of life.

PMID- 24570018
TI  - More with less: A comparative kinematical analysis of Django Reinhardt's
      adaptations to hand injury.
AB  - BACKGROUND: At the age of 18 years, jazz guitarist Django Reinhardt (1910-1953)
      sustained significant burns to his left-hand ring and little fingers; yet,
      subsequently, he relearned to play and achieved international fame, despite his
      injuries. CASE DESCRIPTION AND METHODS: Archive film footage and novel motion
      analysis software were used to compare movements of Django's fretting hand with
      that of six other guitarists of the same genre. FINDINGS AND OUTCOMES: Django
      employed greater abduction of index and middle fingers (-9.11 +/- 6.52 degrees 
      vs -5.78 +/- 2.41 degrees ; p < 0.001) and more parallel alignment of fingers to
      the guitar neck (157.7 +/- 3.37 degrees  vs 150.59 +/- 2.67 degrees ; p < 0.001)
      compared to controls. CONCLUSION: In response to debilitating hand injury, Django
      developed quantifiable compensatory adaptation of function of his remaining
      functional fingers by developing an original playing technique. CLINICAL
      RELEVANCE: Hand function following injury may be optimized by maximizing latent
      degrees of freedom in remaining digits, rather than through extensive surgical
      reconstruction or complex prostheses. Further study of adaptation strategies may
      inform prosthesis design.

PMID- 24570020
TI  - Mandible reconstruction: History, state of the art and persistent problems.
AB  - BACKGROUND: Mandibular reconstruction has been experiencing an amazing evolution.
      Several different approaches are used to reconstruct this bone and therefore have
      a fundamental role in the recovery of oral functions. OBJECTIVES: This review
      aims to highlight the persistent problems associated with the approaches
      identified, whether bone grafts or prosthetic devices are used. A brief summary
      of the historical evolution of the surgical procedures is presented, as well as
      an insight into possible future pathways. STUDY DESIGN: A literature review was
      conducted from September to December 2012 using the PubMed database. The keyword
      used was "mandible reconstruction." Articles published in the last three years
      were included as well as the relevant references from those articles and the
      "historical articles" were referred. This research resulted in a monograph that
      this article aims to summarize. RESULTS: Titanium plates, bone grafts, pediculate
      flaps, free osteomyocutaneous flaps, rapid prototyping, and tissue engineering
      strategies are some of the identified possibilities. The classical approaches
      present considerable associated morbidity donor-site-related problems.
      CONCLUSION: Research that results in the development of new prosthetics devices
      is needed. A new prosthetic approach could minimize the identified problems and
      offer the patients more predictable, affordable, and comfortable solutions.
      CLINICAL RELEVANCE: This review, while affirming the evolution and the good
      results found with the actual approaches, emphasizes the negative aspects that
      still subsist. Thus, it shows that mandible reconstruction is not a closed issue.
      On the contrary, it remains as a research field where new findings could have a
      direct positive impact on patients' life quality. The identification of the
      persistent problems reveals the characteristics to be considered in a new
      prosthetic device. This could overcome the current difficulties and result in
      more comfortable solutions. Medical teams have the responsibility to keep
      patients informed about the predictable problems related with each elected
      approach, even understanding that a perfect reconstruction is a secondary goal
      when compared with maintenance of life.

PMID- 24570021
TI  - Molecular cloning and characterization of enhanced disease susceptibility 1
      (EDS1) from Gossypium barbadense.
AB  - Arabidopsis enhanced disease susceptibility 1 (EDS1) plays an important role in
      plant defense against biotrophic and necrotrophic pathogens. The necrotrophic
      pathogen Verticillium dahliae infection of Gossypium barbadense could lead to
      Verticillium wilt which seriously reduces the cotton production. Here, we cloned
      and characterized a G. barbadense homolog of EDS1, designated as GbEDS1. The full
      length cDNA of the GbEDS1 gene was obtained by the technique of rapid
      amplification of cDNA ends. The open reading frame of the GbEDS1 gene was 1,647
      bp long and encoded a protein of 548 amino acids residues. Comparison of the cDNA
      and genomic DNA sequence of GbEDS1 indicated that this gene contained a single
      intron and two exons. Like other EDS1s, GbEDS1 contained a conserved N-terminal
      lipase domain and an EDS1-specific KNEDT motif. Subcellular localization assay
      revealed that GbEDS1-green fluorescence protein fusion protein was localized in
      both cytosol and nucleus. Interestingly, the transcript levels of GbEDS1 were
      dramatically increased in response to pathogen V. dahliae infection. To
      investigate the role of GbEDS1 in plant resistance against V. dahliae, a
      conserved fragment derived from GbEDS1 was used to knockdown the endogenous EDS1
      in Nicotiana benthamiana by heterologous virus-induced gene silencing. Our data
      showed that silencing of NbEDS1 resulted in increased susceptibility to V.
      dahliae infection in N. benthamiana, suggesting a possible involvement of the
      novelly isolated GbEDS1 in the regulation of plant defense against V. dahliae.

PMID- 24570022
TI  - Brazilian genetic database of chromosome X.
AB  - The X chromosome is a singular source of information in population genetics,
      anthropological research and in forensic cases. Thus, many researchers have been
      interested in characterizing X chromosome markers in different populations. The
      Brazilian Genetic Database of Chromosome X (BGBX--Banco Genetico Brasileiro do
      Cromossomo X) website is freely available in Portuguese and English versions and
      was developed with the main purpose of compiling all Brazilian population genetic
      data for X chromosome short tandem repeats (X-STRs) markers published in
      scientific journals searchable via PubMed. Furthermore, this database presents
      other relevant information concerning X-STRs, such as genetic and physical
      locations, allele structure, nomenclature, mutation rates, primers described in
      the literature and likelihood ratio calculation. The entire scientific community
      is now encouraged to submit their X-STR population genetic data to this website,
      available at http://www.bgbx.com.br. Regarding future prospects of BGBX, the
      authors intend to expand the website with data and information of X-linked
      insertion-deletion polymorphisms.

PMID- 24570023
TI  - Variations analysis of NLGN3 and NLGN4X gene in Chinese autism patients.
AB  - Autism is a neurodevelopmental disorder clinically characterized by impairment of
      social interaction, deficits in verbal communication, as well as stereotypic and
      repetitive behaviors. Several studies have implicated that abnormal
      synaptogenesis was involved in the incidence of autism. Neuroligins are
      postsynaptic cell adhesion molecules and interacted with neurexins to regulate
      the fine balance between excitation and inhibition of synapses. Recently,
      mutation analysis, cellular and mice models hinted neuroligin mutations probably
      affected synapse maturation and function. In this study, four missense variations
      [p.G426S (NLGN3), p.G84R (NLGN4X), p.Q162 K (NLGN4X) and p.A283T (NLGN4X)] in
      four different unrelated patients have been identified by PCR and direct
      sequencing. These four missense variations were absent in the 453 controls and
      have not been reported in 1000 Genomes Project. Bioinformatic analysis of the
      four missense variations revealed that p.G84R and p.A283T were "Probably
      Damaging". The variations may cause abnormal synaptic homeostasis and therefore
      trigger the patients more predisposed to autism. By case-control analysis, we
      identified the common SNPs (rs3747333 and rs3747334) in the NLGN4X gene
      significantly associated with risk for autism [p = 5.09E-005; OR 4.685 (95% CI
      2.073-10.592)]. Our data provided a further evidence for the involvement of NLGN3
      and NLGN4X gene in the pathogenesis of autism in Chinese population.

PMID- 24570024
TI  - SIRT1 promoter polymorphisms as clinical modifiers on systemic lupus
      erythematosus.
AB  - Silent mating type Information Regulator 2 homolog 1 (SIRT1) is a deacetylase
      protein that participates in several physiological processes with importance in
      transcriptional silencing, apoptosis, immune system regulation and inflammation.
      Systemic lupus erythematosus (SLE) is an inflammatory autoimmune disease in which
      upregulated expression of SIRT1 on CD4+ T lymphocytes of active patients has been
      reported. Also, global hypoacetylation of histones H3 and H4, with H3
      hypoacetylation was correlated with a higher disease activity index. SIRT1
      promoter rs12778366 and rs3758391 may account for differential expression of this
      molecule and the role of these variants was investigated in SLE susceptibility
      and morbidity. Genomic DNA was extracted from peripheral blood of 367 SLE
      patients and 290 healthy controls of a Southern Brazilian population. SIRT1
      rs12778366 and rs3758391 were amplified through PCR and genotyped through
      sequencing. No statistically significant differences were observed between
      patients and controls for allelic, genotypic or haplotypic frequencies.
      Nevertheless, SIRT1 rs3758391 was not in Hardy-Weinberg equilibrium, presenting a
      paucity of CT heterozygous both in patients and controls. SLE patients with TT
      and CT genotypes displayed a higher chance of developing lupus nephritis (Pc =
      0.012, OR = 2.04 95 % CI 1.32-3.14) and presented a higher disease activity index
      (Mean rank 170.95 vs 137.26, Pc = 0.006) when compared with CC homozygous
      patients. Our results suggest that SIRT1 rs3758391 modifies SLE morbidity, with
      rs3758391 T allele being a risk factor for nephritis and a higher SLEDAI.
      Nevertheless, it remains to be elucidated how SIRT1 rs3758391 functionally
      influences SLE severity.

PMID- 24570025
TI  - SNP and haplotype analysis of paired box 3 (PAX3) gene provide evidence for
      association with growth traits in Chinese cattle.
AB  - Paired box 3 (PAX3) belongs to the PAX superfamily of transcription factors and
      plays essential roles in the embryogenesis and postnatal formation of limb
      musculature through affecting the survival of muscle progenitor cells. By genetic
      mapping, PAX3 gene is assigned in the interval of quantitative trait loci for
      body weight on bovine BTA2. The objectives of this study were to detect
      polymorphisms of PAX3 gene in 1,241 cattle from five breeds and to investigate
      their effects on growth traits. Initially, three novel single nucleotide
      polymorphisms (SNPs) were identified by DNA pool sequencing and aCRS-RFLP methods
      (AC_000159: g.T-580G, g.A4617C and g.79018Ins/del G), which were located at 5'
      UTR, exon 4 and intron 6, respectively. A total of eight haplotypes were
      constructed and the frequency of the three main haplotypes H1 (TAG), H2 (GCG) and
      H3 (GAG) accounted for over 81.7 % of the total individuals. Statistical analysis
      revealed that the three SNPs were associated with body height and body length of
      Nanyang and Chinese Caoyuan cattle at the age of 6 and/or 12 months old (P <
      0.05), and consistently significant effects were also found in the haplotype
      combination analysis on these traits (P < 0.05). This study presented a complete
      scan of variations within bovine PAX3 gene, which could provide evidence for
      improving the economic traits of cattle by using these variations as potentially
      genetic markers in early marker-assisted selection programs.

PMID- 24570026
TI  - Neutrophil extracellular traps induce endothelial dysfunction in systemic lupus
      erythematosus through the activation of matrix metalloproteinase-2.
AB  - RATIONALE: The structural and functional integrity of the endothelium is crucial
      in maintaining vascular homeostasis and preventing atherosclerosis. Patients with
      systemic lupus erythematosus (SLE) have an increased risk of developing
      endothelial dysfunction and premature cardiovascular disease. Neutrophil
      extracellular trap (NET) formation is increased in SLE and has been proposed to
      contribute to endothelial damage, but the mechanism remains unclear. OBJECTIVE:
      To determine the mechanism by which enhanced NET formation by low-density
      granulocytes (LDGs) in SLE contributes to endothelial damage and disrupts the
      endothelium. RESULTS: The putative role of NET-externalised matrix
      metalloproteinases (MMPs) in altering the functional integrity of the endothelium
      was examined. MMP-9 externalised by lupus LDGs during NET formation specifically
      impaired murine aortic endothelium-dependent vasorelaxation and induced
      endothelial cell apoptosis. Endothelial dysfunction correlated with the
      activation of endothelial MMP-2 by MMP-9 present in NETs, while inhibition of MMP
      2 activation restored endothelium-dependent function and decreased NET-induced
      vascular cytotoxicity. Moreover, immunogenic complexes composed of MMP-9 and anti
      MMP-9 were identified in SLE sera. These complexes, as well as anti-MMP-9
      autoantibodies, induced NETosis and enhanced MMP-9 activity. CONCLUSIONS: These
      observations implicate activation of endothelial MMP-2 by MMP-9 contained in NETs
      as an important player in endothelial dysfunction, and MMP-9 as a novel self
      antigen in SLE. These results further support that aberrant NET formation plays
      pathogenic roles in SLE.

PMID- 24570027
TI  - FMF50: a score for assessing outcome in familial Mediterranean fever.
AB  - BACKGROUND: Colchicine is the main treatment for familial Mediterranean fever
      (FMF). However, biological agents and other treatments are available for patients
      who are unable to receive optimal treatment. OBJECTIVE: To develop outcome
      criteria that define response to treatment. METHODS: Two rounds of Delphi
      exercise were followed by a consensus conference enabling the definition of the
      criteria to be employed. Data for patients with FMF responding and resistant to
      their treatment were obtained from the FMF Arthritis Vasculitis and Orphan
      disease Research in paediatric rheumatology (FAVOR) website. The suggested
      criteria were analysed and validated in this patient cohort.
      Sensitivity/specificity measures and the ability of the score to discriminate
      between patients with active and inactive disease via the best cut-off score were
      calculated by a receiver operating characteristic analysis. RESULTS: Compliance
      with the maximum dose of the drug was considered essential for evaluation of the
      patients. Seven criteria were suggested in the consensus conference. The
      performance of each criterion, in differentiating between resistant and
      responsive patients, was tested. The final set of criteria was defined as at
      least 50% improvement in five of six criteria, without worsening in any one
      defined response to treatment with a very high sensitivity and specificity. The
      items of this FMF50 included: 1. Percentage change in the frequency of attacks
      with the treatment. 2. Percentage change in the duration of attacks with the
      treatment. 3. Patients/parents' global assessment of disease severity (10 cm
      visual analogue scale (VAS)). 4. Physicians' global assessment of disease
      severity (10 cm VAS). 5. Percentage change in arthritis attacks with the
      treatment. 6. Percentage change in C-reactive protein, erythrocyte sedimentation
      rate or serum amyloid A level with the treatment. CONCLUSIONS: The FMF50 produced
      is a user-friendly measurement tool to guide physicians and can be used in
      clinical trials.

PMID- 24570028
TI  - Maternal quercetin administration during gestation and lactation decrease
      endoplasmic reticulum stress and related inflammation in the adult offspring of
      obese female rats.
AB  - PURPOSE: Maternal obesity is a risk factor for metabolic diseases in offspring.
      The aim of this study was to investigate whether quercetin administration during
      gestation and lactation could have any protective effect against the impact of
      maternal obesity on increased sensitivity to obesity and metabolic disorders in
      offspring. METHODS: Female Sprague-Dawley rats were fed a high-fat diet to induce
      obesity. Obese dams were administered 0, 50, 100 or 200 mg/kg body weight (BW)
      quercetin intragastrically during gestation and lactation. Normal weight dams
      were used as controls. The F1 generation was fed with a standard diet after
      weaning, and blood glucose, lipids and inflammatory factors were assessed.
      Expression of biomarkers involved endoplasmic reticulum (ER) stress, and related
      inflammatory pathways in liver and adipose tissues were analyzed at postnatal day
      100. RESULTS: Maternal obesity resulted in increased birth weight, postnatal BW
      gain, hyperglycemia, hyperlipemia, hyperinsulinemia, increased serum levels of
      inflammatory factors, and up-regulated biomarkers involved in ER stress and
      related inflammatory pathways in the offspring. Maternal quercetin intervention
      (QI) had significant ameliorating effects on maternal blood lipids, especially
      cholesterol, which resulted in improved glucose metabolism and insulin
      sensitivity and alleviated ER stress and related inflammation in the grown
      offspring of obese dams. CONCLUSIONS: Maternal QI in obese dams during gestation
      and lactation reduced birth weight and postnatal BW gain in the offspring, and
      helped to improve insulin sensitivity and lipid metabolism of the mature
      offspring via reducing ER stress and related inflammation in the liver and
      adipose tissue.

PMID- 24570030
TI  - Psychiatry residents' experiences with systems-based practice: a qualitative
      survey.
AB  - OBJECTIVE: The aim of this study is to analyze qualitative data collected during
      field-testing of an instrument to assess psychiatric residents' experiences with
      systems-based practice (SBP). METHODS: A total of 237 psychiatry residents from 6
      levels of training in 12 different psychiatry residency training programs
      responded to a 60-item instrument measuring their experiences with SBP during
      residency. Qualitative techniques adapted from content analysis were used to
      review narrative responses to open-ended questions on the instrument. RESULTS:
      Certain themes emerged in the residents' answers reflecting their opinions about
      the opportunities for (and barriers to) performing SBP in their work.
      CONCLUSIONS: Psychiatric residents express an eagerness for opportunities to
      learn about and perform SBP but often feel constrained by the lack of resources,
      teaching, and supervision. Moreover, many residents desire a better understanding
      of healthcare economics and how to factor cost consideration into clinical care.

PMID- 24570031
TI  - Mental health services research training for the next generation of leaders in
      the public health sector: a case study of the UCSF/SFGH Public Psychiatry
      Fellowship.

PMID- 24570029
TI  - Effects of a healthy Nordic diet on plasma 25-hydroxyvitamin D concentration in
      subjects with metabolic syndrome: a randomized, [corrected] controlled trial
      (SYSDIET).
AB  - PURPOSE: At northern latitudes, vitamin D is not synthesized endogenously during
      winter, causing low plasma 25-hydroxyvitamin D (25(OH)D) concentrations.
      Therefore, we evaluated the effects of a healthy Nordic diet based on Nordic
      nutrition recommendations (NNR) on plasma 25(OH)D and explored its dietary
      predictors. METHODS: In a Nordic multi-centre trial, subjects (n = 213) with
      metabolic syndrome were randomized to a control or a healthy Nordic diet
      favouring fish (>=300 g/week, including >=200 g/week fatty fish), whole-grain
      products, berries, fruits, vegetables, rapeseed oil and low-fat dairy products.
      Plasma 25(OH)D and parathyroid hormone were analysed before and after 18- to 24
      week intervention. RESULTS: At baseline, 45 % had vitamin D inadequacy (<50
      nmol/l), whereas 8 % had deficiency (<25 nmol/l). Dietary vitamin D intake was
      increased by the healthy Nordic diet (P < 0.001). The healthy Nordic and the
      control diet reduced the prevalence of vitamin D inadequacy by 42 % (P < 0.001)
      and 19 % (P = 0.002), respectively, without between-group difference (P = 0.142).
      Compared with control, plasma 25(OH)D (P = 0.208) and parathyroid hormone (P =
      0.207) were not altered by the healthy Nordic diet. Predictors for 25(OH)D were
      intake of vitamin D, eicosapentaenoic acids (EPA), docosahexaenoic acids (DHA),
      vitamin D supplement, plasma EPA and plasma DHA. Nevertheless, only vitamin D
      intake and season predicted the 25(OH)D changes. CONCLUSION: Consuming a healthy
      Nordic diet based on NNR increased vitamin D intake but not plasma 25(OH)D
      concentration. The reason why fish consumption did not improve vitamin D status
      might be that many fish are farmed and might contain little vitamin D or that
      frying fish may result in vitamin D extraction. Additional ways to improve
      vitamin D status in Nordic countries may be needed.

PMID- 24570032
TI  - A new reference line in diagnosing a high-riding patella on routine digital
      lateral radiographs of the knee.
AB  - OBJECTIVE: To propose a new reference line in diagnosing a high-riding patella
      (patella alta) on routine digital lateral radiographs of the knee. MATERIALS AND
      METHODS: On 64 routine digital lateral radiographs of adult knees with no bone
      pathology or surgery and over the range of knee flexion between 1.6 degrees  and
      79.1 degrees  (34.4 degrees +/- 16.6 degrees ), the long axis of the superimposed
      egg-shaped femoral condyles was drawn and moved upward to pass through the point
      where the posterior contours of the femoral diaphysis and the femoral condyles
      meet-the posterior reference point-to become a new reference line. Any part of
      the patella crossing the new reference line indicated a high-riding patella. The
      new reference line was compared with the four most common patellar height ratios
      (Insall-Salvati, Grelsamer-Meadows or the modified Insall-Salvati, Caton
      Deschamps, and Blackburne-Peel) for the drawing time, accuracy, and
      reproducibility (intra- and interobserver agreement). RESULTS: The new reference
      line required approximately one-third to one-half of the drawing time compared to
      the most common patellar height ratios, with equal accuracy and complete
      reproducibility. On the contrary, the reproducibility of the most common patellar
      height ratios ranged from poor to moderate, with the best results for the Insall
      Salvati ratio. CONCLUSIONS: The new reference line proved to be a very simple,
      accurate, and reproducible tool in diagnosing a high-riding patella. We believe
      that our preliminary results are an encouraging impetus to more complex research.

PMID- 24570033
TI  - Topiramate add-on for drug-resistant partial epilepsy.
AB  - BACKGROUND: The majority of people with epilepsy have a good prognosis and their
      seizures are controlled by a single antiepileptic drug. However, up to 20% of
      patients from population-based studies and up to 30% from clinical series (not
      population-based) develop drug-resistant epilepsy, especially those with partial
      onset seizures. In this review we summarise the current evidence regarding
      topiramate, an antiepileptic drug first marketed in 1996, when used as an add-on
      treatment for drug-resistant partial epilepsy. This is an updated version of the
      original Cochrane review published in Issue 3, 1999. OBJECTIVES: To evaluate the
      efficacy and safety of topiramate when used as an add-on treatment for people
      with drug-resistant partial epilepsy. SEARCH METHODS: We searched the Cochrane
      Epilepsy Group Specialised Register (June 2013); the Cochrane Central Register of
      Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 5); MEDLINE (1946
      to 2013); SCOPUS (1823 to 2013); ClinicalTrials.gov and ICTRP. We imposed no
      language restrictions. We also contacted the manufacturers of topiramate and
      researchers in the field to identify any ongoing or unpublished studies.
      SELECTION CRITERIA: Randomised, placebo-controlled or active drug controlled add
      on trials of topiramate, recruiting people with drug-resistant partial epilepsy.
      DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials
      for inclusion and extracted the relevant data. We assessed the following
      outcomes: (a) 50% or greater reduction in seizure frequency; (b) seizure freedom;
      (c) treatment withdrawal (any reason); (d) side effects. Primary analyses were
      intention-to-treat and summary risk ratios (RR) with 95% confidence intervals
      (95% CI) are presented. We evaluated dose response in regression models. We
      carried out a 'Risk of bias' assessment for each included study using the
      Cochrane 'Risk of bias' tool and assessed the overall quality of evidence using
      the GRADE approach, which we presented in a 'Summary of findings' table. MAIN
      RESULTS: Eleven trials were included, representing 1401 randomised participants.
      Baseline phases ranged from 4 to 12 weeks and double-blind phases from 11 to 19
      weeks. The RR for a 50% or greater reduction in seizure frequency compared to
      placebo was 2.97 (95% CI 2.38 to 3.72). Dose regression analysis shows increasing
      effect with increasing dose, but found no advantage for doses over 300 or 400 mg
      per day. The RR for seizure freedom (95% CI) compared to placebo was 3.41 (95% CI
      1.37 to 8.51). The RR for treatment withdrawal compared to placebo was 2.44 (95%
      CI 1.64 to 3.62). The RRs for the following side effects indicate that they are
      significantly associated with topiramate: ataxia 2.29 (99% CI 1.10 to 4.77);
      concentration difficulties 7.81 (2.08 to 29.29); dizziness 1.54 (99% CI 1.07 to
      2.22); fatigue 2.19 (99% CI 1.42 to 3.40); paraesthesia 3.91 (1.51 to 10.12);
      somnolence 2.29 (99% CI 1.49 to 3.51); 'thinking abnormally' 5.70 (99% CI 2.26 to
      14.38) and weight loss 3.47 (1.55 to 7.79). Evidence of publication bias was
      found (P-value from the Egger test was P=0.003). We rated all studies included in
      the review as having either low or unclear risk of bias. Overall, we assessed the
      evidence as moderate quality due to the evidence of publication bias. AUTHORS'
      CONCLUSIONS: Topiramate has efficacy as an add-on treatment for drug-resistant
      partial epilepsy in that it is three times more effective compared to a placebo
      in reducing seizures. However, the trials reviewed were of relatively short
      duration and provide no evidence for the long-term efficacy of topiramate. In the
      short term topiramate as an add-on has been shown to be associated with several
      adverse events. The results of this review cannot be extrapolated to monotherapy
      or treatment of other epilepsy types and future research should consider
      examining the effect of dose.

PMID- 24570035
TI  - Thoracolithiasis: a unique autopsy finding.

PMID- 24570036
TI  - Specificity may count: not every aspect of coping self-efficacy is beneficial to
      quality of life among Chinese cancer survivors in China.
AB  - BACKGROUND: General self-efficacy has been shown to be a protective factor of
      cancer survivors' quality of life (QoL). Coping self-efficacy includes multiple
      aspects, such as maintaining positive attitudes, regulating emotion, seeking
      social support, and seeking medical information. How these various aspects are
      related to multiple domains of QoL is unclear. PURPOSE: This study examined the
      associations between different aspects of coping self-efficacy and QoL among
      Chinese cancer survivors. METHODS: A sample of 238 Chinese cancer survivors (mean
      age = 55.7, 74.4 % female) in Beijing, China participated in the survey. Coping
      self-efficacy and QoL were measured by the Cancer Behavior Inventory and Quality
      of Life-Cancer Survivor Instrument. RESULTS: After controlling for demographic
      and disease-related variables, hierarchical regression analyses showed that
      coping self-efficacy in accepting cancer/maintaining a positive attitude was
      positively associated with physical, psychological, and spiritual QoL. Self
      efficacy in affective regulation was positively associated with psychological and
      social QoL, but negatively associated with spiritual well-being. Self-efficacy in
      seeking support was positively associated with spiritual well-being, but
      negatively associated with physical QoL. Self-efficacy in seeking and
      understanding medical information was negatively associated with psychological
      and social QoL. CONCLUSIONS: Our findings imply the specificity of coping self
      efficacy in predicting QOL. Our findings could be helpful for designing future
      interventions. Increasing cancer survivors' self-efficacies in accepting
      cancer/maintaining a positive attitude, affective regulation, and seeking support
      may improve cancer survivors' QoL depending on the specific domains.

PMID- 24570037
TI  - [Universal coverage of health services in Mexico].
AB  - The reforms made in recent years to the Mexican Health System have reduced
      inequities in the health care of the population, but have been insufficient to
      solve all the problems of the MHS. In order to make the right to health
      protection established in the Constitution a reality for every citizen, Mexico
      must warrant effective universal access to health services. This paper outlines a
      long-term reform for the consolidation of a health system that is akin to
      international standards and which may establish the structural conditions to
      reduce coverage inequity. This reform is based on a "structured pluralism"
      intended to avoid both a monopoly exercised within the public sector and
      fragmentation in the private sector, and to prevent falling into the extremes of
      authoritarian procedures or an absence of regulation. This involves the
      replacement of the present vertical integration and segregation of social groups
      by a horizontal organization with separation of duties. This also entails legal
      and fiscal reforms, the reinforcement of the MHS, the reorganization of health
      institutions, and the formulation of regulatory, technical and financial
      instruments to operationalize the proposed scheme with the objective of rendering
      the human right to health fully effective for the Mexican people. 

PMID- 24570038
TI  - Evaluation of Etest performed in Mueller-Hinton agar supplemented with glucose
      for antifungal susceptibility testing of clinical isolates of filamentous fungi.
AB  - Although reference broth microdilution protocol is currently available for
      filamentous fungi antifungal susceptibility testing (AFST), simpler alternatives
      as Etest((r)) tend to be favoured in clinical routine, making their validation of
      utmost importance. In this study, Etest((r)) method using 2% glucose supplemented
      Muller-Hinton agar was compared to the Clinical and Laboratory Standards
      Institute (CLSI) M38-A2 protocol for filamentous fungi AFST. The echinocandins,
      caspofungin and anidulafungin, the azoles voriconazole and posaconazole, and the
      polyene amphotericin B were tested against 48 Aspergillus spp., seven Fusarium
      spp., one Beauveria bassiana and three Paecilomyces lilacinus isolates. The
      majority of the isolates were susceptible to the antifungals tested, and the
      overall level of agreement between the CLSI and Etest methods was 71.9% for one
      dilution and 99.7% when using two dilutions. Since interpretative breakpoints for
      filamentous fungi employing the CLSI or Etest methods are not available yet, the
      established epidemiological cut-off values for Aspergillus spp. were used to
      distinguish wild-type isolates from those with acquired resistance mechanisms.
      Forty-five Aspergillus strains did not evidence resistance mutations.

PMID- 24570039
TI  - Wild animals as sentinels of Paracoccidioides brasiliensis in the state of Rio
      Grande do Sul, Brazil.
AB  - Paracoccidioides brasiliensis, a dimorphic pathogenic fungus, causes the
      principal form of systemic mycosis in Brazil. The literature furnishes only
      limited data on the ecology of this fungus in the state of Rio Grande do Sul, the
      southernmost state of Brazil. The purpose of this study was to evaluate the
      prevalence of fungal infection in wild animals, using serological tests and using
      the animals as sentinels of the presence of P. brasiliensis in three specified
      mesoregions of Rio Grande do Sul. A total of 128 wild animals from the three
      mesoregions were included in the study. The serum samples were evaluated by
      immunodiffusion and the enzyme-linked immunosorbent assay (ELISA) technique to
      detect anti-gp43 antibodies from P. brasiliensis. Two conjugates were tested and
      compared with the ELISA technique. Although no positive samples were detected by
      immunodiffusion, 26 animals (20%), belonging to 13 distinct species, were found
      to be seropositive by the ELISA technique. The seropositive animals were from two
      mesoregions of the state. The results were similar according to the gender, age,
      and family of the animals, but differed significantly according to the conjugate
      used (p < 0.001), showing more sensitivity to protein A-peroxidase than to
      protein G-peroxidase. The finding that wild animals from the state of Rio Grande
      do Sul are exposed to P. brasiliensis suggests that the fungus can be found in
      this region despite the often-rigorous winters, which frequently include below
      freezing temperatures.

PMID- 24570040
TI  - Granulomatous invasive aspergillosis of paranasal sinuses masquerading as
      actinomycosis and review of published literature.
AB  - Cutaneous aspergillosis is a common systemic mycosis affecting immunosuppressed
      patients. Here, we describe a novel morphological type of cutaneous aspergillosis
      in a young immunocompetent woman who presented with a chronic history of multiple
      nodules and discharging sinuses over left side of the face, mimicking
      cervicofacial actinomycosis. Skin biopsy showed granulomatous inflammation, and
      of septate fungal hyphae with acute-angled branching, morphologically resembling
      Aspergillus. This was confirmed on fungal culture as Aspergillus flavus. 

PMID- 24570043
TI  - PCR detection of Neospora caninum in water buffalo foetal tissues.
AB  - The seroprevalence of Neospora caninum was surveyed by an ELISA kit on two water
      buffalo herds of Southern Italy. Seropositive samples were detected in 47% and
      59% of individuals, respectively, thus indicating high level of exposure to the
      parasite even if the possibility of vertical transmission cannot be excluded.
      Tissue samples collected from three aborted fetuses from the same herds were
      investigated for N. caninum presence by PCR assays targeting the 18S and the Nc5
      DNA sequences, respectively. Both methods have shown the presence of N. caninum
      DNA in heart and brain. Sequencing of the Nc5 genomic DNA confirmed the presence
      of N. caninum in the samples; phylogenetic analysis of the obtained sequences
      showed high homology among the Neospora recovered from different samples. The
      present study suggests an important role of N. caninum as a possible abortive
      agent for water buffaloes. 

PMID- 24570042
TI  - Prevalence and molecular characterisation of the sessile serrated adenoma in a
      subset of the Chinese population.
AB  - AIMS: The incidence and mortality rates from right-sided colorectal cancers
      (CRCs) have not decreased in recent years. It is very likely that a significant
      proportion of these cancers evolve from undetected sessile serrated adenomas
      (SSAs). The prevalence and molecular features of the SSAs in the Chinese
      population have seldom been investigated. METHODS: We retrospectively reviewed
      the colonoscopy database and pathology archives in our medical centre.
      Adenomatous polyposis coli (APC) and beta-catenin expressions were examined in 28
      right hyperplastic polyps (RHPs) and 21 SSAs by immunohistochemical staining. The
      mutations of BRAF, KRAS, APC and beta-CATENIN were analysed by direct sequencing.
      The methylation status of APC promoter in these polyps was analysed by
      methylation-specific PCR and bisulfite sequencing. Samples of left hyperplastic
      polyps, traditional adenomas and CRC were used as controls. RESULTS: SSAs
      accounted for 4.9% of serrated polyps and 1.0% of all colorectal polyps.
      BRAF((V600E)) mutations were found in 14.3% of SSAs and 7.1% of RHPs. Nuclear
      accumulation of beta-catenin was seen in 28.6% of SSAs and 17.9% of RHPs. APC
      mutations were detected in 57.1% of SSAs and 67.9% of RHPs. APC methylation was
      detected in 14.3% of RHPs and 23.8% of SSAs. CONCLUSIONS: The prevalence of SSAs
      in a subset of the Chinese population is much lower than that in the Western
      population. BRAF((V600E)) mutation is not a frequent event in right colon
      serrated polyps in a subset of the Chinese population. APC mutation is possibly
      the main cause for the Wnt signalling activation in right colon serrated polyps.

PMID- 24570041
TI  - Successful treatment of a necrotizing fasciitis patient caused by Mucor indicus
      with amphotericin B and skin grafting.
AB  - Cutaneous mucormycosis, an uncommon disease caused by Mucorales, predominantly
      occurs in immunocompromised host. The present case is a primary cutaneous
      mucormycosis due to Mucor indicus in an immunocompetent individual. It is with
      the features of necrotizing fasciitis over the right pretibial area. We are
      presenting this case owing to its rarity and the successful treatment with
      amphotericin B and skin grafting. 

PMID- 24570044
TI  - Comparative study for the detection of antibodies to Neospora caninum in milk and
      sera in dairy cattle in southern Romania.
AB  - The study aimed to assess the within-herd Neospora caninum exposure in dairy
      cattle in southern Romania, based on the detection of specific antibodies in milk
      and serum. A total of 104 paired samples of milk and serum were collected from
      four dairy farms. Individual samples were analyzed for N. caninum antibodies by
      ELISA: IDEXX Neospora Ab (Idx) (three farms: A, B, C; n = 60) and ID-VET Lab
      (Idv) (farm D; n = 44). Additionally, four pooled milk samples, one per each farm
      (A, B, C) and a composed one (A+B+C), were analyzed with Idx ELISA. Optimized cut
      off values for milk samples were determined by receiver operating characteristic
      (ROC) analysis, with serum results considered as true status. The agreement was
      expressed by K values. The overall seroprevalence of N. caninum infection was 45%
      in the farms tested by Idx ELISA and 56.8% in the farm tested by Idv ELISA. A
      good agreement between serum and milk was obtained for both ELISA kits (K = 0.72
      and 0.77, respectively). The specificity and sensitivity at optimized cut-off of
      S/P>0.704 for Idx and S/P%>7.966% for Idv were 100% and 70.37% for Idx and 89.47%
      and 88% for Idv. Testing pooled milk samples, there were identified as N. caninum
      positive the dairy farms with a 15% or higher within-herd seroprevalence at the
      cut-off value of S/P>0.51. This is the first study in Romania in which milk
      samples were tested to determine the N. caninum infection status in dairy farms,
      providing a base for further researches. 

PMID- 24570045
TI  - Generation of adenosine tri-phosphate in Leishmania donovani amastigote forms.
AB  - Leishmania, the causative agent of various forms of leishmaniasis, is the
      significant cause of morbidity and mortality. Regarding energy metabolism, which
      is an essential factor for the survival, parasites adapt to the environment under
      low oxygen tension in the host using metabolic systems which are very different
      from that of the host mammals. We carried out the study of susceptibilities to
      different inhibitors of mitochondrial electron transport chain and studies on
      substrate level phosphorylation in wild-type L. donovani. The amastigote forms of
      L. donovani are independent on oxidative phosphorylation for ATP production.
      Indeed, its cell growth was not inhibited by excess oligomycin and
      dicyclohexylcarbodiimide, which are the most specific inhibitors of the
      mitochondrial Fo/F1-ATP synthase. In contrast, mitochondrial complex I inhibitor
      rotenone and complex III inhibitor antimycin A inhibited amastigote cell growth,
      suggesting the role of complex I and complex III in cell survival. Complex II
      appeared to have no role in cell survival. To further investigate the site of ATP
      production, we studied the substrate level phosphorylation, which was involved in
      the synthesis of ATP. Succinate-pyruvate couple showed the highest substrate
      level phosphorylation in amastigotes whereas NADH-fumarate and NADH-pyruvate
      couples failed to produce ATP. In contrast, NADPH-fumarate showed the highest
      rate of ATP formation in promastigotes. Therefore, we can conclude that substrate
      level phosphorylation is essential for the survival of amastigote forms of
      Leishmania donovani. 

PMID- 24570046
TI  - Monogenean parasites from fishes of the Vaal Dam, Gauteng Province, South Africa.
      I. Winter survey versus summer survey comparison from Labeo capensis (Smith,
      1841) and Labeo umbratus (Smith, 1841) hosts.
AB  - Indigenous South African Labeo spp. show promise with regard to development of
      semi-intensive aquaculture, yet little research on their monogenean fauna has
      been conducted. Ecological aspects of monogenean fauna of the moggel Labeo
      umbratus (Smith 1841) and the Orange River mudfish Labeo capensis (Smith 1841),
      as recorded during both winter and summer sampling surveys, are reported here.
      Fish were collected using gill nets, euthanized and gills removed and examined to
      both quantify parasite numbers and distribution on the gills. Results obtained
      support the hypothesis that gill site preference is not due to active choice for
      a particular attachment site, but rather a result of water flow over gills during
      respiration in conjunction with fish behaviour and habitat use. Interaction
      between individual elements investigated (temperature effects, parasite
      population dynamics and host population dynamics) may be largely responsible for
      seasonal differences in infection statistics of monogenean parasites. Such
      interactions should be investigated in future large scale ecological studies, in
      combination with experimental studies, to further elucidate these effects. 

PMID- 24570047
TI  - Immunomodulation of ALT-2 and TLR may collude in antigen specific T cell
      hyporesponsiveness: proposed mechanism for elevated IL-10 levels in Balb/C mice.
AB  - ALT-2, a novel antigen belonging to the chromadorea ALT-2 family of the filarial
      nematode is proved to clear filarial parasites in Jirds. In order to increase the
      protection efficacy by stimulating the cell mediated immunity, MPLA a detoxified
      derivative of LPS known to induce the cellular response, was used in this study
      as an adjuvant on mice models. ALT-2+MPLA formulation elicited a high titer of
      total IgG antibody, with profoundly increased levels of IgG2b. Reduced splenocyte
      proliferation was observed in immunized group when compared to control groups
      which could be attributed to many in vivo factors. The levels of IFN-gamma were
      high in unstimulated MPLA group compared to ALT-2 stimulated MPLA group,
      suggesting that the ALT-2 antigen suppressed the IFN-gamma levels. A high level
      of IL-10 was induced by the ALT-2+MPLA formulation, which inhibited the
      production of Th2 cytokines (IL-4, IL-5) and also reduced the Th1 cytokine (IFN
      gamma, IL-2) levels which are not in vogue with the classical MPLA adjuvant
      formulation. We propose a mechanism for this immunomodulation which involves a
      diminished expression of TLR-4, by which the filarial parasites have evolved to
      evade host immune mechanism. 

PMID- 24570048
TI  - Infective larvae of Rhabdiasidae (Nematoda): comparative morphology of seven
      European species.
AB  - The morphology of infective third-stage larvae of Rhabdias bufonis, R.
      rubrovenosa, R. sphaerocephala, R. fuscovenosa, R. elaphe, Entomelas entomelas
      and E. dujardini is described. The sheath structure in the studied larvae
      appeared to be similar to that described in other species of the family
      Rhabdiasidae, its chequered aspect being caused by a combination of outer
      longitudinal striations and inner longitudinal as well as transverse ridges. The
      larvae were similar in general morphology but differed in the presence/absence of
      anterior apical protuberances (pseudolabia), the shape and ornamentation of the
      tail tip, and the structure of lateral alae in the caudal region of the body. No
      relationship between the morphological characters of the larvae of the studied
      species and their taxonomic position or specificity of adult parasites to a
      particular host group was observed. Regardless, the larvae of each species can be
      identified by a combination of morphological peculiarities in the anterior and
      caudal regions of the body. 

PMID- 24570049
TI  - Digenea in notothenioid fish in the Beagle Channel (Magellanic sub-region, sub
      Antarctica).
AB  - Fish of five species of Notothenioidei (104 specimens), Cottoperca trigloides,
      Patagonotothen brevicauda, P. longipes, P. tessellata and Champsocephalus esox,
      caught in the Beagle Channel (Magellanic sub-region, sub-Antarctica) were
      infected with Digenea of nine species (1130 specimens). Faunistic data on the
      occurrence of all nine parasites are provided. The most abundant digenean species
      was Macvicaria magellanica found in the intestine of three host species of the
      genus Patagonotothen. The second most abundant digenean species was
      Elytrophalloides oatesi found in the stomach of four host species, with exception
      of P. brevicauda. Three digenean species: Stenakron kerguelense, Whitegonimus
      ozoufae and Genolinea bowersi, were more abundant in fish caught at the harbor of
      Ushuaia (depth 7-9 m), remaining six species: M. magellanica, Neolepidapedoides
      subantarcticus, Postmonorchis variabilis, Derogenes varicus, E. oatesi and
      Lecithaster macrocotyle, in the eastern mouth of the Beagle Channel (depth 30 m).

PMID- 24570050
TI  - Larval trematodes infecting the South-American intertidal mud snail Heleobia
      australis (Rissooidea: Cochliopidae).
AB  - Larval trematodes infecting the snail Heleobia australis (Cochliopidae) from the
      Bahia Blanca estuary, Argentina were surveyed for two years. A total of 7,504
      snail specimens was dissected and the larval stages of 15 different trematodes
      were recovered and examined morphologically. These larvae included four species
      that had previously been reported from H. australis in Brazil, Uruguay, and
      Argentina: the heterophyid Ascocotyle (Phagicola) longa and the microphallids,
      Maritrema bonaerense, Maritrema orensense, and Microphallus simillimus. Three
      other species, the echinostomatid Stephanoprora uruguayensis, the microphallid
      Levinseniella cruzi, and the psilostomid Psilochasmus oxyurus are reported here
      for the first time as parasites of H. australis. Eight other trematodes found in
      H. australis are described and placed in the appropriate superfamilies, families
      or genera (Cryptogonimidae, Apocreadiidae, Aporocotylidae, Notocotylidae,
      Haploporidae, Renicolidae, Himasthla, and Renicola). The prevalence of the
      trematode taxa infecting H. australis in the Bahia Blanca estuary was low (<3%)
      with a single exception (M. simillimus; >20%). Microphallidae were the richest
      and the most prevalent family, probably because of the high abundance of crabs -
      the second-intermediate hosts of certain microphallid species - and the
      considerable diversity of gulls. Here we compare the parasite assemblage found in
      the H. australis from Bahia Blanca estuary with other parasite assemblages
      infecting Heleobia spp. and other rissooids from the rest of the world. 

PMID- 24570051
TI  - Quill mites of the subfamily Picobiinae (Acari: Syringophilidae) associated with
      woodpeckers (Aves: Piciformes: Picidae).
AB  - The paper contains a review of quill mites of the subfamily Picobiinae (Acari:
      Prostigmata: Syringophilidae) associated with woodpeckers (Aves: Piciformes:
      Picidae). Three new species are described: Picobia mentalis Skoracki et Unsoeld
      sp. nov. from Picus mentalis Temminck, Neopicobia ea Skoracki et Unsoeld sp. nov.
      from Celeus flavus (St. Mueller) (type host), C. elegans (St. Mueller), C.
      torquatus (Boddaert), and Neopicobia freya Skoracki et Unsoeld sp. nov. from
      Dryocopus galeatus (Temminck) (type host) and Piculus rubiginosus (Swainson).
      Additionally, six new host species for Picobia heeri Haller, 1878 and 12 new host
      species for Picobia dryobatis (Fritsch, 1956) are reported. A complete list of
      the picobiines parasitising birds of the family Picidae is presented in the
      tabular form. 

PMID- 24570052
TI  - Cosmocercoides himalayanus sp. nov. (Nematoda, Cosmocercidae) in Duttaphrynus
      himalayanus (Amphibia, Anura) from Dehradun (Uttarakhand), India.
AB  - Cosmocercoides himalayanus sp. nov. (Nematoda, Cosmocercidae) from the large
      intestine of Duttaphrynus himalayanus (Amphibia, Anura) from Dehradun, India is
      described and illustrated. Cosmocercoides himalayanus sp. nov. represents the
      21st species assigned to the genus and the 9th species from the Oriental
      biogeographical region. Cosmocercoides himalayanus sp. nov. differs from the
      previously described Oriental species in number and position of rosette papillae;
      it is the only species possessing 24 or more rosette papillae to have 4
      postcloacal papillae. In addition, a list of species assigned to Cosmocercoides
      is provided; however, C. fotedari Arya, 1992 is removed from the genus and until
      further study is considered a species inquirenda. 

PMID- 24570053
TI  - Targeting tams-1 gene results in underestimation of Theileria annulata infection
      in diseased cattle in Egypt.
AB  - Tropical theileriosis is considered one of the most economically important tick
      borne diseases that cause significant mortality and morbidity to livestock. In
      the context of epidemiological studies on livestock in Egypt, this report
      investigated the spread of Theileria annulata among diseased farm cows (Bos
      indicus) over one year. Blood samples collected from 130 cows were investigated
      by routine staining and 64 samples were investigated by PCR assay using two
      different probes targeting tams-1 gene. Microscopy revealed the infection of
      33.8% of animals with Theileria while PCR detected infection in 51% of animals
      with one primer pair and the other primer pair detected the infection in 31% of
      animals. Combined PCR results indicated the infection of 68.8% of animals with T.
      annulata. Seasonal fluctuation of parasite infection was evident with the highest
      infection percentage and prevalence recorded during summer based on both
      microscopy and PCR data. For the first time, the current study reports the
      presence of two T. annulata isolates based on tams-1 gene partial sequence in
      Egypt. Targeting polymorphic genes for parasite detection may result in
      underestimation of infection and target gene diversity has to be considered. The
      high infection with these pathogens in the clinically ill cows necessitates
      implementing serious programs to minimize their economic burden on the Egyptian
      farming industry. 

PMID- 24570054
TI  - A new species of Unilatus (Platyhelminthes: Monogenoidea) from the gills of
      Leporacanthicus galaxias Isbrucker et Nijssen (Siluriformes: Loricariidae) from
      Brazil.
AB  - Unilatus irae sp. nov. (Dactylogyridae) is described from the gills of the
      armored catfish, Leporacanthicus galaxias Isbrucker et Nijssen (Loricariidae:
      Ancistrinae), from Guama river, Para State, Brazil. The new species can be
      differentiated from its cogeneners by the combination of the following features:
      anterior anchor with well-developed superficial root, inconspicuous deep root,
      shaft bent at midpoint, forming angle of approximately 60 degrees , evenly short
      curved point; posterior anchor with inconspicuous roots, sclerotized cap of base
      with small protuberance for articulation to posterior bar; evenly curved shaft
      and short point; anterior bar broadly V-shaped, with small posteromedial
      projection; and posterior bar anteriorly expanded on it midportion, with expanded
      ends slightly curved in posterior direction. 

PMID- 24570056
TI  - Parasites communities in the clingfish Gobiesox marmoratus from central Chile.
AB  - This study investigated the factors (i.e., season, locality, sampling year, total
      length and maturity stage of the hosts) that might influence the structure of
      parasite populations and communities in the clingfish Gobiesox marmoratus. The
      parasite community was described and analyzed using numerical descriptors, such
      as prevalence, intensity and species richness, between factors previously
      mentioned. A total of 260 clingfish were collected from 2 localities of central
      Chile, four seasons and during 3 year cycles (from July 2006 to July 2009). In
      the whole clingfish sample, 668 parasites were found, which belonged to 14
      parasite taxa; 9 of them were new records in G. marmoratus. Parasite
      infracommunity richness ranged 0-3 species, although 1 trematode species,
      Helicometrina nimia, represented 80% of all parasites collected and was the most
      abundant and prevalent parasite species. The average of parasite abundance and
      intensity (+/- SD) was 2.5 +/- 8.2 and 7.5 +/- 12.7, respectively. Generalized
      linear model showed that parasite communities were influenced by season,
      locality, sampling year, and maturity stage when considering the abundance and
      intensity of parasites. For the parasite richness, only the locality and maturity
      of fish was determinant for explaining the differences. The populations and
      communities of the parasite variations were variable due to differences in fish
      body length because prevalence, abundance and intensity of parasites
      significantly correlated with the fish body length. Concordantly, maturity fish
      were longer than immature fish. Thus, clingfish from El Tabo were longest and
      mature, which harbored higher parasite richness than those fish from Las Cruces. 

PMID- 24570055
TI  - Infections with cardiopulmonary and intestinal helminths and sarcoptic mange in
      red foxes from two different localities in Denmark.
AB  - Monitoring parasitic infections in the red fox is essential for obtaining
      baseline knowledge on the spread of diseases of veterinary and medical
      importance. In this study, screening for cardiopulmonary and intestinal helminths
      and sarcoptic mange (Sarcoptes scabiei) was done on 118 foxes originating from
      two distinct localities in Denmark, (Copenhagen) greater area and southern
      Jutland. Fifteen parasite species were recorded in 116 foxes (98.3%), nine
      parasitic species are of zoonotic potential. Parasite diversity was greater in
      foxes of Copenhagen in terms of overall parasite species richness and species
      richness of all helminth groups individually: trematodes; cestodes; and
      nematodes. Six parasite species were recovered from foxes of Copenhagen, but not
      from foxes of Southern Jutland: Echinochasmus perfoliatus; Echinostoma sp.;
      Pseudamphistomum truncatum; Dipylidium caninum; Angiostrongylus vasorum; and
      Sarcoptes scabiei, but Toxascaris leonina was only recorded in foxes of southern
      Jutland. A high prevalence and abundance of A. vasorum in foxes of Copenhagen was
      observed. The prevalence of four nematode species; Eucoleus (Capillaria)
      aerophilus, Uncinaria stenocephala, Toxocara canis, and Crenosoma vulpis, in
      foxes of both localities were comparable and ranging from 22.9% to 89%. The
      prevalence of Mesocestoides sp. was significantly higher in foxes of Copenhagen.
      Taenia spp. were detected using morphological and molecular analysis, which
      revealed the dominance of T. polyacantha in foxes of both localities. Infections
      with sarcoptic mange were evident only among foxes of Copenhagen (44.9%), which
      significantly affected the average weight of the infected animals. Further
      remarks on the zoonotic and veterinary implications of the parasites recovered
      are given. 

PMID- 24570057
TI  - New species of Orientatractis (Nematoda: Atractidae), new species of Rondonia
      (Nematoda: Atractidae) and other helminths in Austrochaperina basipalmata (Anura:
      Microhylidae) from Papua New Guinea.
AB  - Two new nematode species, Orientatractis hamabatrachos sp. nov. and Rondonia
      batrachogena sp. nov. (Nematoda: Atractidae), from the gastrointestinal tract of
      Austrochaperina basipalmata (Anura: Microhylidae) collected in Papua New Guinea
      are described. Orientatractis hamabatrachos sp. nov. is characterized by the
      presence of the cephalic end armed with 4 wellsclerotized structures, consisting
      of 2 "horns" extending outward and downward and immediately below a single well
      sclerotized spine. It differs from 5 congeners in spicule lengths and caudal
      papillae arrangements. Rondonia batrachogena sp. nov. is characterized by the
      presence of a female cloaca. It differs from 2 congeners primarily in body size.
      Orientatractis hamabatrachos sp. nov. and Rondonia batrachogena sp. nov.
      represent the first species assigned to either genus found to infect anurans or
      to occur in the Australo-Papuan region. 

PMID- 24570058
TI  - Molecular analysis of lungworms from European bison (Bison bonasus) on the basis
      of small subunit ribosomal RNA gene (SSU).
AB  - Dictyocaulosis (Nematoda: Trichostrongyloidea) is a widespread parasitosis of the
      European bison (Bison bonasus) inhabiting Bialowieza Primeval Forest. Bearing in
      mind the current coexistence of bison with wild cervids, and with domestic
      ruminants in the 19th and 20th century, the need arose for molecular
      identification of lungworm species. Molecular analysis was done on adult
      lungworms that were obtained from the respiratory track of four free-roaming
      bison euthanized as a part of the population health control program. As the
      result of the study four identical small subunit-ribosomal RNA gene sequences
      from the lungworms were obtained and deposited in GenBank as sequence, 1708 bp
      long (GenBank KC771250). Comparative analysis of the SSU rRNA sequences revealed
      the European bison to be a host for the bovine lungworm Dictyocaulus viviparus.

PMID- 24570059
TI  - Toxocariasis and lung function: relevance of a neglected infection in an urban
      landscape.
AB  - Toxocariasis has been highlighted as a potentially important neglected infection
      of poverty in developed countries that experience substantive health disparities
      such as the United States. An association between Toxocara infection and lung
      function, in concert with a relatively high prevalence of infection, may mark an
      important mechanism by which this infection could contribute significantly to the
      differential morbidity across different socioeconomic groups and landscapes. To
      assess the potential relevance of this infection in a dense urban environment, we
      measured the association between forced expiratory volume in 1 second (FEV1) and
      serology diagnosed Toxocara infection in a sample of US-born New York City
      residents. We identified a significant independent association between Toxocara
      infection and lung function, wherein those with previous Toxocara infection had a
      236.9 mL reduced FEV1 compared to those without Toxocara infection even after
      adjusting for age, sex, ethnicity, level of education, smoking status, body mass
      index, and pet ownership. These findings from New York City corroborate similar
      findings in a national sample and, while the cross-sectional data preclude a
      direct causal relationship, this study identifies a potentially important
      neglected infection in a dense urban landscape.

PMID- 24570060
TI  - A PCR method targeting internal transcribed spacers: the simultaneous detection
      of Babesia bigemina and Babesia bovis in cattle.
AB  - In this study, two pairs of oligonucleotide primers were designed according to
      the nucleotide sequence of the internal transcribed spacers (ITSs) of Babesia
      bigemina and B. bovis isolates from China. The primers were used in a multiplex
      PCR to detect parasite DNA in blood samples from cattle. There was no cross
      reactions with B. ovata, B. major, B. sp. Kashi, Theileria annulata, T. sergenti,
      T. sinensis or normal bovine DNA. The sensitivity of multiplex PCR assay was 1 pg
      and 10 pg DNA for B. bigemina and B. bovis, respectively. A total of 260 field
      blood samples collected from cattle in five provinces of China were analyzed by
      multiplex PCR and light microscopy. PCR testing revealed that 7.3% (19/260) and
      5.8% (15/260) of cattle were positive for B. bigemina and B. bovis and 1.2%
      (3/260) of cattle were co-infected with B. bigemina and B. bovis. Using light
      microscopy, 2.3% (6/260) and 1.5% (4/260) of cattle were infected by B. bigemina
      and B. bovis, respectively, and no co-infection was found. The results showed
      that the multiplex PCR developed in the present study could be an alternative
      diagnostic tool for the detection of B. bovis and B. bigemina infection in
      cattle. 

PMID- 24570061
TI  - Three new records of copepods (Siphonostomatoida) parasitic on marine fishes of
      Iraq, including the relegation of two species of Lernanthropinus to
      Lernanthropinus temminckii (von Nordmann, 1864).
AB  - Three parasitic copepods (Siphonostomatoida) belonging to three different genera
      were recovered from marine fishes of Iraq, and are listed here as new records.
      The sea lice Caligus epinepheli Yamaguti, 1936 (Caligidae) was collected from the
      Japanese threadfin bream, Nemipterus japonicus (Bloch). It had been frequently
      reported from teleost fishes around the world. The second record, comprising male
      and female, was another caligid, rarely caught from fishes - Hermilius
      longicornis Bassett-Smith, 1898, collected from the giant catfish, Netuma
      thalassina (Ruppell). This paper features the first description of the male of
      the latter species. The third record was the lernanthropid, Lernanthropinus
      temminckii (von Nordmann, 1864) (Lernanthropidae), redescribed based on the
      specimens collected from the greater lizard fish, Saurida tumbil (Bloch)
      (Synodontidae). In order to clarify its taxonomic status, our specimen was
      compared with the holotype of L. gibbosus (Pillai, 1964) from the collections of
      Zoological Survey of India, Kolkata, and the syntypes of L. sauridae Do in Ho and
      Do, 1985 and L. temminckii from the collections of the Smithsonian Institution,
      Washington D.C. We found similarities in the morphology of the body, mouthparts,
      and legs 1-4 in three above-mentioned species. The prominent feature, the
      setation pattern of legs 1 and 2 was similar in all the female specimens
      examined. In the light of this, we formally relegate L. gibbosus and L. sauridae
      to synonymy with L. temminckii. Another important similarity is that
      Lernanthropinus gibbosus, L. sauridae, and L. temminckii have exclusively been
      parasitic on lizardfishes (Synodontidae). The attachment site of all three
      copepods reported form Iraq were the gill filaments. 

PMID- 24570062
TI  - A novel approach to control brown dog tick, Rhipicephalus sanguineus using
      sustained release poly-E-caprolactone-pheromone microspheres.
AB  - Control of brown dog tick, Rhipicephalus sanguineus was attempted by utilizing
      sustained release preparations of synthetic analogues of assembly pheromones. The
      assembly pheromone, in defined ratio, was encapsulated using poly-E-caprolactone
      by water-in-oil-in-water double emulsion solvent evaporation technique. In the in
      vitro bioassay, percent mortality with test microspheres was 95.6, 64 and 44
      among the unfed larvae, unfed nymph and unfed adults respectively, 24 hours post
      exposure. Field trials were carried out to evaluate the efficacy of microspheres
      in luring and killing environmental stages of R. sanguineus in dog
      houses/kennels. Engorged and unfed stages in the environment were found adhered
      and dead on the specially designed lure. 

PMID- 24570063
TI  - Ecology and seasonal variation of parasites in wild Aequidens tetramerus, a
      Cichlidae from the Amazon.
AB  - This study is the first investigation on seasonal dynamics of parasites component
      community of the Aequidens tetramerus from an Amazon River tributary, in Northern
      Brazil. A total of 239,2407 parasites were recovered from 92 hosts examined from
      February to October 2011. Such parasites included Ichthyophthirius multifiliis,
      Tripartiella tetramerii and Trichodina nobilis (Protozoa), Dolops longicauda
      (Argulidae), Gussevia alioides, Gussevia disparoides (Monogenoidea), Digenea
      metacercarie, Pseudoproleptus larvae, Anisakidae larvae (Nematoda),
      Proteocephalidea plerocercoid (Eucestoda) and Gorytocephalus spectabilis
      (Acanthocephala). Ciliates were the most dominant and abundant taxon, while
      cestodes were the least prevalent. The parasites showed seasonal variation in
      their infection dynamics associated with environmental changes during the
      Amazonian drainage season, except the infection with I. multifiliis. The
      parasites community in A. tetramerus was also characterized by higher diversity,
      species richness and uniformity during the drainage season when compared to
      Amazon flood season. With the exception of T. tetramerii, these parasite species
      are new records for A. tetramerus. 

PMID- 24570064
TI  - Anisakids of seals found on the southern coast of Baltic Sea.
AB  - In the present study 5 grey seals (Halichoerus grypus), 3 common seals (Phoca
      vitulina) and 1 ringed seal (Pusa hispida) bycaught or stranded on the Polish
      Baltic Sea coast in years 2000-2006 were investigated for the infestation of
      parasitic anisakid nematodes. 749 of anisakids were found. The most common were:
      Contracaecum osculatum (59.3%) and Pseudoterranova decipiens (31.0%). There were
      also small numbers of Anisakis simplex (0.8%). After performing RFLP three
      sibling species were found. C. osculatum was identified as C. osculatum C, P
      decipiens was identified as P. decipiens sensu stricto and A. simplex - A.
      simplex sensu stricto. Nematodes found in seals were mostly in L4 and adult life
      stage - both of them were equal with some minor variations among the specimens.
      Sex ratio was also equal, but there was slight excess of males in some cases.
      There was a minority of L3 larvae belonging to A. simplex species (0.8%). 

PMID- 24570065
TI  - Parasites of the head of Scomber colias (Osteichthyes: Scombridae) from the
      western Mediterranean Sea.
AB  - The metazoan parasite assemblage of the head of 30 specimens of the Atlantic chub
      mackerel (Scomber colias) from the western Mediterranean Sea was analysed. Eight
      species of parasites were found, four mazocraeid monogeneans: Grubea cochlear
      (prevalence = 10%), Kuhnia scombercolias (59%), K. scombri (52%), Pseudokuhnia
      minor (86%); three didymozoid trematodes: Nematobothrium cf. faciale (21%), N.
      filiforme (41%), N. scombri (7%); and one laerneopodid copepod: Clavelissa
      scombri (7%). Results were compared with previously published data from 14
      localities of the eastern Mediterranean Sea and the Atlantic Ocean, using non
      parametric univariate and multivariate analyses, and the whole parasite fauna of
      S. colias was compared with that of the congeners (S. australasicus, S. japonicus
      and S. scombrus). Parasites showed to reflect the biogeographical and
      phylogenetic history of host. From a methodological point of view, the use of
      both non-parametric univariate and multivariate techniques proved to be effective
      tools to detect dissimilarities between parasite assemblages. 

PMID- 24570066
TI  - Oral inoculation of live or dead third-stage larvae of Anisakis simplex in rats
      suggests that only live larvae induce production of antibody specific to A.
      simplex.
AB  - Live Anisakis simplex third-stage larvae (L3) penetrate gastrointestinal mucosa
      after they are ingested in raw or undercooked seafood, thereafter causing
      gastrointestinal manifestations and allergic manifestations such as urticaria and
      anaphylaxis. These allergic reactions are mediated by specific IgE to L3
      allergens, especially excretory-secretory (ES) allergens. Recent evidences
      suggest that only live larvae can cause allergic reactions, although cases
      attributable to ingestion of cooked, frozen seafood have been reported. Therefore
      the risk of Anisakis-associated hypersensitivity by ingestion of properly cooked
      and frozen fish remains controversial. No prior report describes the kinetics of
      antibody production in experimental animals after oral inoculation with dead L3.
      This study used ELISA to assess antibody production in rats inoculated orally
      with dead L3. Positive absorbance value in IgG, IgM, and IgE specific to ES
      antigen from L3 were found in rats inoculated with live L3 but not with dead L3
      (frozen, heated, cut, or homogenized). At one week post re-inoculation with live
      or frozen L3 to the initially sensitized rats, the absorbance value of the
      specific IgM and IgE to ES antigen elevated quickly and highly in rats that had
      been re-inoculated with live L3, but they decreased slightly or did not change in
      rats inoculated with frozen L3. These results suggest that only ingestion of live
      L3 can produce the specific antibody and induce initial and secondary
      sensitizations to L3. 

PMID- 24570067
TI  - Adaptation and immunogenicity of Cryptosporidium parvum to immunocompetent mice.
AB  - The adaptation and immunogenisity of Cryptosporidium parvum isolated from
      Siberian chipmunks (SC1 strain) in immunocompetent (ICR) mice were examined. The
      oocysts were received to the severe combined immunodeficiency (SCID) mice by
      repeated passage. The oocysts collected from the 18th SCID mice were inoculated
      to 5 ICR mice. The mice began to shed oocysts from 6 days after inoculation, the
      patency was 5 days, and the maximum oocysts per gram of feces (OPG) value was
      10(4). The maximum of OPG value was gradually increased by successive passage,
      and finally that in the 22nd mice reached 10(6) (patency: 11 days). It is
      considered that these results indicate completion of their adaptation to ICR
      mice. To examine the immunogenicity of C. parvum to ICR mice, 8 groups of 5 mice
      each were inoculated with 1.3 * 10(6) oocysts of SC1 strain, which were collected
      after adaptation to SCID mice. All groups shed oocysts from 6th day, and their
      patency was from 8 to 12 days. On the 21st day after the primary infection, these
      mice were challenged with 1.3 * 10(6) oocysts. No oocysts shed from any groups,
      although 2 control groups shed oocysts from the 6th day, and their OPG values
      were more than 10(6). These results suggest that this strain has strong
      immunogenicity against ICR mice. Therefore, the immunological healthy mice were
      considered a useful experimental model to investigate immunological and drug
      treatments in the strain of C. parvum.

PMID- 24570068
TI  - High occurrence of Cryptosporidium ubiquitum and Giardia duodenalis genotype E in
      sheep from Brazil.
AB  - In this paper we report the occurrence of zoonotic species of Cryptosporidium (C.
      ubiquitum and C. parvum subtype IIaA15G2R1) and the host-specific Giardia
      duodenalis genotype E in a sheep farm from Brazil. Fecal specimens were collected
      from 100 animals and screened for the presence of G. duodenalis and
      Cryptosporidium spp. by enzyme immunoassay (EIA) and polymerase chain reaction
      (PCR). Restriction fragment length polymorphism (RFLP) and sequence analysis of
      selected samples was used to confirm the species and to characterize the
      isolates. Of 100 specimens, 34 were positive for Giardia (34%) and 25 were
      positive for Cryptosporidium (25%). The prevalence of Giardia and Cryptosporidium
      was higher in lambs than in ewes. Co-infection was observed in 14% of animals.
      All G. duodenalis isolates belonged to genotype E. The genetic characterization
      performed in 22 Cryptosporidium-positive samples revealed the presence of
      zoonotic C. ubiquitum and C. parvum in 76% (19/25) and 12% (3/25) of infected
      animals, respectively. The presence of zoonotic Cryptosporidium subtypes in lambs
      was of epidemiological and public health relevance. 

PMID- 24570069
TI  - Whole-body single-frequency bioimpedance analysis in pediatric hemodialysis
      patients.
AB  - BACKGROUND: We hypothesized that the percent change in resistance (%RDelta) from
      bioimpedance analysis (BIA) measurements during hemodialysis (HD) can provide
      information on pediatric HD patients' hydration status. METHODS: Whole-body
      single-frequency BIA measurements were obtained before HD, each hour on HD, and
      after HD during two HD sessions. Pre-and post-HD weights, blood pressures, Crit
      Line(r) measurements, and intradialytic symptoms were collected on the day of the
      BIA measurements. RESULTS: One hundred and thirty BIA measurements were obtained
      from 14 HD patients. The group was 43 % girls, and the mean age was 13.2 +/- 4.4
      years. Percent change in resistance was 13.5 +/- 10.8 % at the end of HD; %RDelta
      correlated with percent body weight change (%BWDelta) following HD (r = -0.83, P
      < 0.01), as well as with percent blood volume change (%BVDelta) (r = -0.79, P <
      0.01). The %RDelta was similar between patients with and without hypertension
      immediately before HD and was greater in those with intradialytic symptoms (19.1
      +/- 7.7 %) than in those without (9.9 +/- 11.2 %) (P = 0.02). Patients with left
      ventricular hypertrophy (LVH) had lower %RDelta (7.2 +/- 9.7 %) than those
      without (19.5 +/- 7.7 %) (P = 0.03). Left ventricular mass index (LVMI) also
      correlated strongly with %RDelta (r = -0.79, P = 0.004) and %BWDelta (r = 0.82, P
      = 0.002). CONCLUSIONS: Our study showed that %RDelta strongly correlates with
      %BWDelta and %BVDelta and that %RDelta also correlated with intradialytic
      symptoms and LVMI.

PMID- 24570070
TI  - Tonic inhibition by G protein-coupled receptor kinase 2 of Akt/endothelial nitric
      oxide synthase signaling in human vascular endothelial cells under conditions of
      hyperglycemia with high insulin levels.
AB  - G protein-coupled receptor kinase 2 (GRK2) participates together with beta
      arrestins in the regulation of G protein-coupled receptor signaling, but emerging
      evidence suggests that GRK2 can interact with a growing number of proteins
      involved in signaling mediated by other membrane receptor families under various
      pathologic conditions. We tested the hypothesis that GRK2 may be an important
      contributor to vascular endothelial dysfunction in diabetes. Human umbilical
      venous endothelial cells (HUVECs) were exposed to high glucose and high insulin
      (HG/HI) to mimic insulin-resistant diabetic conditions. GRK2 expression and
      membrane translocation were up-regulated under HG/HI conditions. HG/HI did not
      modify activation of Akt or endothelial nitric-oxide synthase (eNOS), but GRK2
      inhibitor or small interfering RNA (siRNA) resulted in an increase in Akt and
      eNOS activation in HUVECs exposed to HG/HI. Extracellular signal-regulated kinase
      1/2 (ERK1/2) activation was increased after exposure to HG/HI, which was
      prevented by GRK2 inhibitor or siRNA. ERK1/2-mediated GRK2 phosphorylation at Ser
      670 confirmed that ERK1/2 participated in a negative feedback regulatory loop. In
      human embryonic kidney 293T cells that overexpressed GRK2, Akt activity was
      unchanged, whereas ERK1/2 activity was raised. The effect of GRK inhibitor
      treatment on Akt/eNOS signaling was associated with membrane translocation of
      beta-arrestin 2. The experiments with beta-arrestin 2 siRNA showed that beta
      arrestin 2 may act as a positive modulator of Akt/eNOS signaling. Our studies
      reveal that GRK2, which is up-regulated by HG/HI, leads to a tonic inhibition of
      the insulin Akt/eNOS pathway in endothelial cells. We provide new insights into
      the pathogenesis of diabetes-associated vascular endothelial dysfunction. 

PMID- 24570071
TI  - Tolvaptan delays the onset of end-stage renal disease in a polycystic kidney
      disease model by suppressing increases in kidney volume and renal injury.
AB  - Tolvaptan, a selective vasopressin V2 receptor antagonist, slows the increase in
      total kidney volume and the decline in kidney function in patients with the
      results of the Tolvaptan Efficacy and Safety in Management of Autosomal Dominant
      Polycystic Kidney Disease and Outcome (TEMPO) 3:4 trial. However, it was unclear
      which dose of tolvaptan was optimal or whether tolvaptan was able to delay
      progression to end-stage renal disease (ESRD). Here we examined the relationship
      with aquaresis and the inhibitory effect on cyst development in short-term
      treatment and mortality as an index of ESRD in long-term treatment with tolvaptan
      using DBA/2FG-pcy mice, an animal model of nephronophthisis. With short-term
      treatment from 5 to 15 weeks of age, tolvaptan (0.01-0.3% via diet) dose
      dependently enhanced aquaresis, prevented increases in kidney weight and cyst
      volume, and was associated with significant reductions in kidney cAMP levels and
      extracellular signal-regulated kinase activity. Maximal effects of tolvaptan on
      aquaresis and the prevention of development of polycystic kidney disease (PKD)
      were obtained at 0.1%. Interestingly, tolvaptan also dose-dependently reduced
      urinary neutrophil gelatinase-associated lipocalin levels in correlation with the
      kidney volume. With long-term treatment from 5 to 29 weeks of age, tolvaptan
      significantly attenuated the increase in kidney volume by up to 50% and reduced
      urinary albumin excretion. Furthermore, tolvaptan significantly reduced the
      mortality rate to 20%, compared with 60% in the control group. These data
      indicate that tolvaptan may delay the onset of ESRD in PKD by suppressing the
      increases in kidney volume and renal injury, providing a promising treatment for
      PKD. 

PMID- 24570072
TI  - Clinico-pathological features and outcomes of patients with propylthiouracil
      associated ANCA vasculitis with renal involvement.
AB  - OBJECTIVE: To retrospectively investigate clinico-pathological features and
      outcomes of patients with renal involvement in propylthiouracil (PTU)-associated
      antineutrophil cytoplasmic autoantibody (ANCA) vasculitis (PTU-AAV). METHODS:
      Clinico-pathological features and outcomes of 12 patients (female 11, average age
      32.4 +/- 13.8 years) who developed AAV after treatment with PTU were collected
      and analyzed. ANCA was detected by both immunofluorescence (IF) and enzyme linked
      immunosorbent assay (ELISA). All patients had renal biopsy. RESULTS: Twelve
      patients received PTU for 2-264 months (median 42 months) when PTUAAV was
      diagnosed. All patients had positive serum P-ANCA, 11 of them were MPO-ANCA, 1
      was MPO and PR3-ANCA double positive. All patients presented with hematuria and
      proteinuria, 5 of them had gross hematuria, urine protein was 1.9 +/- 1.6 g/24 h,
      7 of 12 (58.3%) patients had renal dysfunction, among them 3 needed initial renal
      replacement therapy. Renal biopsy showed pauci-immune segmental necrotizing
      crescentic glomerulonephritis in ten patients, segmental necrotizing
      glomerulonephritis superimposed on membranous nephropathy in two patients. All
      patients withdrew PTU and received steroid and immunosuppressive therapy. After a
      median follow-up of 42 months (range 21-86), 3 patients developed to ESRD, 7
      patients entered complete renal remission. Serum ANCA turned negative only in 2
      patients, 10 patients had persistent positive serum ANCA. Three patients relapsed
      with the elevation of serum ANCA level. CONCLUSION: Renal damage of PTU-AAV could
      be pauci-immune necrotizing crescentic glomerulonephritis, and necrotizing
      glomerulonephritis coexisted with membranous nephropathy. Most patients had
      persistent positive serum ANCA and had a risk of relapse and progression to ESRD
      even after PTU withdrawal and immunosuppressive therapy.

PMID- 24570073
TI  - A load volume suitable for reaching dialysis adequacy targets in anuric patients
      on 4-exchange CAPD.
AB  - INTRODUCTION: Continuous ambulatory peritoneal dialysis (CAPD) depuration indexes
      are targeted to get a minimum total weekly peritoneal urea clearance (Kt/V) of
      1.70 and creatinine clearance/1.73 m(2) (pCrCL) of 50 l. In anuric patients these
      targets are difficult to achieve. Since dialysis volumes (load, VOL(in); drain,
      VOL(out)) are the main determinants of peritoneal clearances (pCLs), we aimed to
      estimate the minimum volumes required to fulfill these targets in anuric
      patients. METHODS: Sixty-nine CAPD anuric patients from eight dialysis units were
      observed retrospectively. Demographic data, dialysis schedule, VOLs and
      depuration indexes were recorded. The relationship between normalized VOLs and
      pCLs was estimated by linear regression analysis as a whole (95 % confidence
      interval of the fit) and stratified by tertiles of body weight (BW) and surface
      area (BSA). RESULTS: Mean weekly pKt/V was 1.89 +/- 0.29, pCrCL 52.9 +/- 8.0,
      VOL(in) 32.9 +/- 5.3 ml/kg and VOL(out) 37.4 +/- 6.7 ml/kg exchange. VOL(in) and
      VOL(out) correlated with depuration indexes only if normalized. A VOL(in) of 28.5
      ml/kg exchange (27.0-30.0) was associated with a pKt/V of 1.70, and a VOL(in) of
      29.5 (26.5-31.5) with a pCrCL of 50 l, with a VOL(out) of 31.7 ml/kg (29.5-33.5)
      and 32.4 (27.2-35.5), respectively. Smaller patients needed a lower normalized
      VOL(in)/exchange to obtain pKt/V = 1.70 (1st vs. 2nd vs. 3rd BW tertiles: 28.3
      vs. 28.9 vs. 29.0 ml/kg; BSA tertiles: 1,696 vs. 1,935 vs. 2,086 ml/1.73).
      CONCLUSIONS: In CAPD anuric patients VOL(in) prescription could be tailored to
      body mass to reach the minimum depuration target. Normalized VOL(in) might be
      prescribed in slightly higher doses (from 27 to 30 ml/kg exchange) for patients
      with higher body mass.

PMID- 24570076
TI  - The aortic valve: structure, complications and implications for transcatheter
      aortic valve replacement.
AB  - The aortic valve operates in a complex haemodynamic environment, opening and
      closing over 100,000 times a day. When complications arise, such as aortic
      stenosis, prognosis can be very poor, leading to death within the first few
      years. Surgical valve replacement is currently the standard treatment for aortic
      stenosis. A thorough understanding of the anatomy and function of the native
      valve is imperative when developing a prosthetic replacement that can withstand
      the complex demands of the heart. This review focuses on the anatomy, structure
      and disease of the aortic valve and the implications for a transcatheter aortic
      valve replacement (TAVR). Current complications with TAVR, such as major vascular
      bleeding, conduction disturbances and patient-prosthesis mismatch (PPM), can be
      overcome by reducing the delivery profile and through the use of more accurate
      imaging technologies to work towards a fully functional and durable prosthesis.

PMID- 24570075
TI  - Identification of androgen receptor splice variant transcripts in breast cancer
      cell lines and human tissues.
AB  - The androgen receptor (AR) is widely expressed in human tissues and has
      biological function in many male and female organs. In particular, the AR plays a
      critical role in the biology and pathology of the prostate gland. AR activity
      inhibits breast growth and has pleiotropic actions in breast cancer that are
      subtype-dependent. Expression of AR splice variants (ARVs) and their role in
      prostate carcinogenesis has been elucidated in recent studies. We hypothesised
      that ARVs are also expressed in breast cancers and other hormone sensitive
      tissues. Herein, the expression of five previously identified ARV transcripts
      with documented transcriptional capacity (AR-V1, -V3, -V4, -V7, and -V9) was
      examined in 6 breast (MFM223, MDA-MB-453, MDA-MB-231, ZR75.1, MCF-7, T47D), two
      prostate (VCaP, LNCaP), and one liver (HepG2) cancer cell lines, a human
      embryonic kidney cell line (HEK293), and a panel of RNAs representing 21
      different human tissues. Four ARVs (V1, V3, V7, V9) were detected to some degree
      in almost all cell lines and tissues. In addition, four novel ARVs containing a
      cryptic exon 9 (CE9) were detected in MDA-MB-453 and VCaP cells. Sequencing of
      ARV amplicons revealed a single nucleotide substitution within CE3 in lung and
      placental tissue samples that could be translated as an Ile (ATT)>Val (GTT)
      substitution in the AR-V7 variant protein. Collectively, these data provides
      insight into the potential complexity of AR transcriptional splicing events in
      breast cancer cell lines and diverse human tissues, thereby establishing a
      rationale for further exploration of ARVs in breast cancer and other human
      pathologies. 

PMID- 24570077
TI  - Evaluation of the activated clotting time and activated partial thromboplastin
      time for the monitoring of heparin in adult extracorporeal membrane oxygenation
      patients.
AB  - INTRODUCTION: Historically, the activated clotting time (ACT) has been the
      preferred monitoring test of the heparin effect in extracorporeal membrane
      oxygenation (ECMO) patients. However, few adult studies have evaluated its
      correlation to the heparin dose or other monitoring tests, such as the activated
      partial thromboplastin time (aPTT). This retrospective study sought to evaluate
      the correlation between the heparin dose and these monitoring tests. METHODS:
      Patients administered a heparin drip during ECMO were included in this study. The
      primary endpoints were the correlation between heparin dose and ACT or aPTT and
      the relationship between paired ACT and aPTT samples. RESULTS: Forty-six patients
      met the criteria for study inclusion. A better correlation was observed for
      heparin dose and aPTT (Pearson product-moment correlation coefficient (r) = 0.43 
      0.54) versus ACT (r = 0.11 - 0.14). Among the paired sample data, ACT values did
      not differ significantly between Groups two (aPTT 60 - 75 seconds) and three
      (aPTT >75 seconds). CONCLUSION: The heparin dose correlated better with aPTT
      relative to ACT and, thus, may be considered a more effective tool for the dosing
      of heparin in adult ECMO patients. Paired ACT and aPTT sample data suggested a
      poor relationship between these two anticoagulant monitoring tests.

PMID- 24570078
TI  - Effect of nicardipine on renal function following robot-assisted laparoscopic
      radical prostatectomy in patients with pre-existing renal insufficiency.
AB  - OBJECTIVE: To investigate the renoprotective effect of nicardipine in patients
      with pre-existing renal insufficiency undergoing robot-assisted laparoscopic
      radical prostatectomy (RALRP). METHODS: Men with preoperative renal insufficiency
      (estimated glomerular filtration rate [eGFR] <60 ml/min per 1.73 m(2)) were
      enrolled and randomized to receive either 0.5 ug/kg per min nicardipine
      continuous infusion (nicardipine group) or normal saline (control group) during
      RALRP. Renal function was determined by eGFR and serum creatinine concentration.
      RESULTS: Serum creatinine levels on postoperative days (POD) 1 and 3 were
      significantly lower than baseline values in the nicardipine group (n = 50). In
      the control group (n = 50), eGFR was significantly higher on POD 3 than baseline,
      and was significantly higher than baseline on POD 1 and 3 in the nicardipine
      group. The change in eGFR from baseline to POD 1 was significantly higher in the
      nicardipine group than the control group. CONCLUSION: Continuous infusion of
      nicardipine during RALRP improved postoperative renal function on POD 1 in
      patients with pre-existing renal insufficiency.

PMID- 24570080
TI  - Inappropriate prescribing of combination inhalers in Northern Ireland:
      retrospective cross-sectional cohort study of prescribing practice in primary
      care.
AB  - BACKGROUND: Asthma management guidelines advocate a stepwise approach to asthma
      therapy, including the addition of a long-acting bronchodilator to inhaled
      steroid therapy at step 3. This is almost exclusively prescribed as inhaled
      combination therapy. AIMS: To examine whether asthma prescribing practice for
      inhaled combination therapy (inhaled corticosteroid/long-acting beta2-agonist
      (ICS/LABA)) in primary care in Northern Ireland is in line with national asthma
      management guidelines. METHODS: Using data from the Northern Ireland Enhanced
      Prescribing Database, we examined initiation of ICS/LABA in subjects aged 5-35
      years in 2010. RESULTS: A total of 2,640 subjects (67%) had no inhaled
      corticosteroid monotherapy (ICS) in the study year or six months of the preceding
      year (lead-in period) and, extending this to a 12-month lead-in period, 52% had
      no prior ICS. 41% of first prescriptions for ICS/LABA were dispensed in January
      to March. Prior to ICS/LABA prescription, in the previous six months only 17% had
      a short-acting beta2-agonist (SABA) dispensed, 5% received oral steroids, and 17%
      received an antibiotic. CONCLUSIONS: ICS/LABA therapy was initiated in the
      majority of young subjects with asthma without prior inhaled steroid therapy.
      Most prescriptions were initiated in the January to March period. However, the
      prescribing of ICS/LABA did not appear to be driven by asthma symptoms (17%
      received SABA in the previous 6 months) or severe asthma exacerbation (only 5%
      received oral steroids). Significant reductions in ICS/LABA, with associated cost
      savings, would occur if the asthma prescribing guidelines were followed in
      primary care.

PMID- 24570081
TI  - The Global Alliance against Respiratory Diseases (GARD) Country Report.

PMID- 24570082
TI  - Validation of the COPD Diagnostic Questionnaire in an Australian general practice
      cohort: a cross-sectional study.
AB  - BACKGROUND: The gold standard for the diagnosis of chronic obstructive pulmonary
      disease (COPD) is spirometry, but there are barriers to its use in primary care.
      AIMS: To externally validate the COPD Diagnostic Questionnaire (CDQ) as a
      diagnostic tool in patients at increased risk in Australian general practice and
      to compare its performance with other CDQ validation studies. METHODS: Patients
      were recruited from 36 general practices in Sydney, Australia. Former or current
      smokers aged 40-85 years with no prior COPD diagnosis were invited to a case
      finding appointment with the practice nurse. The CDQ was collected and pre- and
      postbronchodilator spirometry was performed. Cases for whom complete CDQ data
      were present and the spirometry met quality standards were analysed. RESULTS: Of
      1,631 patients who attended case-finding recruitment, 1,054 (65%) could be
      analysed. Spirometry showed 13% had COPD. The ability of the CDQ to discriminate
      between patients with and without COPD was fair, represented by the area under
      the receiver operating characteristic curve of 0.713. With a CDQ cut-off point
      value of 16.5 the sensitivity was 80% and specificity 47% and, at a cut-off point
      value of 19.5, the sensitivity was 63% and specificity 70%. CONCLUSIONS: The CDQ
      did not discriminate between patients with and without COPD accurately enough to
      use as a diagnostic tool in patients at increased risk of COPD in Australian
      general practice. Further research is needed on the value of the CDQ as a tool
      for selecting patients for spirometry.

PMID- 24570083
TI  - Impact of switching to new spirometric reference equations on severity staging of
      airflow obstruction in COPD: a crosssectional observational study in primary
      care.
AB  - BACKGROUND: Severity of airflow obstruction in chronic obstructive pulmonary
      disease (COPD) is based on forced expiratory volume in one second expressed as
      percentage predicted (FEV1%predicted) derived from reference equations for
      spirometry results. AIMS: To establish how switching to new spirometric reference
      equations would affect severity staging of airflow obstruction in the Dutch
      primary care COPD patient population. METHODS: Spirometry tests of 3,370 adults
      aged >40 years with obstruction (postbronchodilator FEV1/forced vital capacity
      (FVC) <0.70) were analysed. The presence and severity of obstruction were defined
      using Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria.
      Postbronchodilator FEV1%predicted was calculated using three reference equations:
      corrected European Community of Steel and Coal (ECSC) (currently recommended in
      Dutch primary care), Swanney et al., and Global Lung Initiative (GLI).
      Discordances between severity classifications based on these equations were
      analysed. RESULTS: We studied 1,297 (38.5%) females and 2,073 males. Application
      of contemporary reference equations (i.e. Swanney and GLI) changed the GOLD
      severity stages obtained with the ECSC equations, mostly into milder stages.
      Severity of airflow obstruction was staged differently in 14.0% and 6.3%,
      respectively, when the Swanney et al. and GLI reference equations were applied.
      CONCLUSIONS: Compared with the (corrected) ECSC equations, switching to more
      contemporary reference equations would result in lower FEV1 predicted values and
      affect interpretation of spirometry by reclassifying 6-14% of primary care COPD
      patients into different (mostly milder) severity stages. If and how this will
      affect GPs' treatment choices in individual patients with COPD requires further
      investigation.

PMID- 24570084
TI  - Performance of a brief asthma control screening tool in community pharmacy: a
      cross-sectional and prospective longitudinal analysis.
AB  - BACKGROUND: Guidelines recommend basing asthma management on assessment of asthma
      control. Validated control tools, while suitable for clinical research, may not
      be feasible for routine use in primary care. AIMS: To describe the performance of
      the Pharmacy Asthma Control Screening tool (PACS) compared with the Asthma
      Control Questionnaire (ACQ-6). METHODS: Data were obtained from a multicentre
      study of a community pharmacy asthma management programme in Australia, with
      three or four visits over six months. Eligible participants had suboptimal asthma
      control or no recent visit to their doctor for asthma. Asthma control was
      assessed at baseline and at six months with the PACS tool and ACQ-6. RESULTS: A
      total of 570 patients were enrolled and 398 (70%) completed the programme. The
      average ACQ-6 score was 1.58+/-1.05 at baseline and 0.96+/-0.88 (n=392) after six
      months. Sensitivity and specificity of PACS 'poor control' for not well
      controlled asthma (ACQ- 6 >1.0) were 0.92 and 0.66, respectively, at baseline and
      0.76 and 0.83 at six months. Agreement between the two tools at six months was
      moderate (kappa=0.54). Both tools showed highly significant change during the
      study (p<0.0001 for each), but agreement between the change in the two tools was
      only fair (kappa=0.31). CONCLUSIONS: This study shows that a simple asthma
      control screening tool is feasible for use in community pharmacies and has good
      sensitivity for identifying patients with not well-controlled asthma. Screening
      tools are useful in primary care to identify patients who require more detailed
      assessment of their asthma status, whereas for monitoring asthma control over
      time, a continuous control measure is more appropriate.

PMID- 24570085
TI  - Feasibility of dynamic CT-based adenosine stress myocardial perfusion imaging to
      detect and differentiate ischemic and infarcted myocardium in an large
      experimental porcine animal model.
AB  - The purpose of the study is feasibility of dynamic CT perfusion imaging to detect
      and differentiate ischemic and infarcted myocardium in a large porcine model. 12
      Country pigs completed either implantation of a 75 % luminal coronary stenosis in
      the left anterior descending coronary artery simulating ischemia or balloon
      occlusion inducing infarction. Dynamic CT-perfusion imaging (100 kV, 300 mAs),
      fluorescent microspheres, and histopathology were performed in all models. CT
      based myocardial blood flow (MBFCT), blood volume (MBVCT) and transit constant
      (Ktrans), as well as microsphere's based myocardial blood flow (MBFMic) were
      derived for each myocardial segment. According to histopathology or microsphere
      measurements, 20 myocardial segments were classified as infarcted and 23 were
      ischemic (12 and 14 %, respectively). Across all perfusion states, MBFCT strongly
      predicted MBFMic (beta 0.88 +/- 0.12, p < 0.0001). MBFCT, MBVCT, and Ktrans were
      significantly lower in ischemic/infarcted when compared to reference myocardium
      (all p < 0.01). Relative differences of all CT parameters between affected and
      non-affected myocardium were higher for infarcted when compared to ischemic
      segments under rest (48.4 vs. 22.6 % and 46.1 vs. 22.9 % for MBFCT, MBVCT,
      respectively). Under stress, MBFCT was significantly lower in infarcted than in
      ischemic myocardium (67.8 +/- 26 vs. 88.2 +/- 22 ml/100 ml/min, p = 0.002). In a
      large animal model, CT-derived parameters of myocardial perfusion may enable
      detection and differentiation of ischemic and infarcted myocardium. 

PMID- 24570086
TI  - Femtosecond laser-assisted selective reduction of neovascularization in rat
      cornea.
AB  - Nonlinear multiphoton absorption induced by focusing near infrared (NIR)
      femtosecond (fs) laser pulses into a transparent cornea allows surgery on
      neovascular structures with minimal collateral damage. In this report, we
      introduce an fs laser-based microsurgery for selective treatment of rat corneal
      neovascularizations (in vivo). Contiguous tissue effects are achieved by scanning
      a focused laser pulse below the corneal surface with a fluence range of 2.2-8.6
      J/cm(2). The minimal visible laser lesion (MVL) threshold determined over the
      corneal neovascular structures was found to be 4.3 J/cm(2). Histological and
      optical coherence tomography examinations of the anterior segment after laser
      irradiations show localized degeneration of neovascular structures without any
      unexpected change in adjacent tissues. Furthermore, an approximately 30 %
      reduction in corneal neovascularizations was observed after 5 days of fs laser
      exposure. The femtosecond laser is thus a promising tool for minimally invasive
      intrastromal surgery with the aid of a significantly smaller and more
      deterministic photodisruptive energy threshold for the interaction between the fs
      laser pulse and corneal neovascular structures.

PMID- 24570088
TI  - Is carbon dioxide laser vaporization a valuable tool in the management of oral
      leukoplakia? A survey at an oncology hospital.

PMID- 24570087
TI  - Importance of laser-induced breakdown spectroscopy for hard tissues (bone, teeth)
      and other calcified tissue materials.
AB  - Laser-induced breakdown spectroscopy (LIBS) as a sensitive optical technique
      capable of fast multielemental analysis proved to be a versatile tool in
      different applications. It became visible in the analytical atomic spectroscopy
      scene in the late 1980s and since then, its applications having been developed
      continuously in different field of science and technology including biomedical
      science. Here, we review the use and importance of LIBS for trace element
      determination in different calcified tissue materials. In this article, we have
      also reported a comprehensive review of the recent progress of biomedical
      applications of LIBS. 

PMID- 24570089
TI  - Use of bariatric outcomes longitudinal database (BOLD) to study variability in
      patient success after bariatric surgery.
AB  - BACKGROUND: This study was conducted to determine the contributions of various
      predictors to the large variations in absolute weight loss and percent body mass
      index (BMI) loss after bariatric surgery. METHODS: The data source was the
      Bariatric Outcomes Longitudinal Database(SM) by the Surgical Review Corporation.
      Eligibility criteria included a first bariatric surgery for adjustable gastric
      band (AGB), Roux-en-Y gastric bypass (RYBG), or sleeve gastrectomy (SG) between
      January 2007 and February 2010; age 21 years or older; presurgery BMI > 30 kg/m2;
      and at least one preoperative visit within 6 months and at least one
      postoperative visit 30 days or more after surgery. Potential predictor variables
      included procedural details, patient demographics, comorbidities, and prior
      surgical history. Linear regression models of absolute weight loss and %BMI loss
      were fitted at 12, 18, and 24 months. The 12-month absolute weight loss endpoint
      was then chosen for a more in-depth analysis of variability through variable
      transformations and separate models by procedure. RESULTS: A total of 31,443 AGB,
      40,352 RYGB, and 2,194 SG patients met all inclusion criteria. Regression models
      explained 37 to 55% of the variability in %BMI loss and 52 to 65% of variability
      in absolute weight loss. The key predictors for absolute weight loss at 12 months
      were procedure (44.8%) and baseline weight (18.5%), with 34.2% of the variability
      unexplained. Other significant predictors, each of which accounted for <1% of
      variability, included age, race, and diabetes. CONCLUSIONS: Research on
      additional sources of variability is still needed to help explain the remaining
      differences in outcomes after bariatric surgery.

PMID- 24570090
TI  - The role of cognitive function in postoperative weight loss outcomes: 36-month
      follow-up.
AB  - BACKGROUND: Cognitive dysfunction is associated with reduced postoperative weight
      loss up to 2 years following surgery, though the role of cognition at more
      extended follow-up is not yet understood. Thirty-six months following bariatric
      surgery, we retrospectively compared obese and non-obese patients on 12-week
      postoperative cognitive performance. We hypothesized that early postoperative
      cognitive dysfunction would predict higher body mass index (BMI) and lower
      percent weight loss (%WL) in the total sample at 36 month follow-up. MATERIALS
      AND METHODS: Fifty-five individuals undergoing bariatric surgery completed
      cognitive testing at preoperative baseline and serial postoperative timepoints,
      including 12 weeks and 36 months. Cognitive test scores were normed for
      demographic variables. Percent weight loss (%WL) and body mass index (BMI) were
      calculated at 36-month follow-up. RESULTS: Adjusting for gender, baseline
      cognitive function, and 12-week %WL, 12-week global cognitive test performance
      predicted 36 month postoperative %WL and BMI. Partial correlations revealed
      recognition memory, working memory, and generativity were most strongly related
      to weight loss. CONCLUSION: Cognitive function shortly after bariatric surgery is
      closely linked to extended postoperative weight loss at 36 months. Further work
      is necessary to clarify mechanisms underlying the relationship between weight
      loss, durability, and cognitive function, including contribution of adherence, as
      this may ultimately help identify individuals in need of tailored interventions
      to optimize postoperative weight loss.

PMID- 24570091
TI  - Axis I disorders in adjustable gastric band patients: the relationship between
      psychopathology and weight loss.
AB  - BACKGROUND: Bariatric surgery candidates have higher rates of co-morbid
      psychological illnesses than those in the general population. The effect of
      weight loss on these illnesses is unclear. METHODS: This prospective
      observational study explored psychiatric co-morbidities and weight loss outcomes
      in 204 gastric banding surgery candidates. Psychiatric co-morbidities were
      assessed prior to surgery and 2 years post-surgery. One hundred and fifty
      patients (74%) completed assessments at both time points. RESULTS: At baseline,
      39.7% of the patients met the criteria for a current axis I disorder as defined
      by the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM
      IV). Mood disorders were the most frequent (26.5%), followed by anxiety disorders
      (15.2%) and binge eating disorder (13.2%). Preoperative psychopathology predicted
      clinical psychopathology at 2 years. No preoperative or post-operative axis I
      disorder was significantly related to weight loss at 2 years. The frequency of
      current axis I disorders decreased significantly from 39.7% preoperatively to 20%
      2 years post-surgery. CONCLUSIONS: The point prevalence of psychopathology in
      this sample of Australian bariatric candidates is high. Psychopathology,
      preoperatively and at 2 years of follow-up, was not associated with weight loss
      at 2 years.

PMID- 24570092
TI  - Leukotrienes in pulmonary arterial hypertension.
AB  - Leukotrienes (LTs) are lipid mediators derived from the 5-lipoxygenase (5-LO)
      pathway of arachidonic acid metabolism and are markers and mediators of pulmonary
      inflammation. Research over the past two decades has established that LTs
      modulate inflammation in pulmonary arterial hypertension (PAH). The purpose of
      this review was to summarize the current knowledge of LTs in the pathophysiology
      of PAH and to highlight a recent study that advances our understanding of how
      leukotriene B4 (LTB4) specifically contributes to pulmonary vascular remodeling.
      The results of these studies suggest that pharmacological inhibition of LT
      pathways, especially LTB4, has high potential for the treatment of PAH.

PMID- 24570093
TI  - Early septic shock induces loss of oxidative phosphorylation yield plasticity in
      liver mitochondria.
AB  - We aimed to study the change in mitochondrial oxidative phosphorylation
      efficiency occurring at the early stage of septic shock in an experimental model.
      Thirty-six male Wistar rats were divided into two groups. In the first group, a
      cecal ligation and puncture (CLP) was carried out to induce septic shock for 5 h.
      The second group includes sham-operated rats and constitutes the control group.
      Blood gas analysis, alanine amino transferase, and lactic acid dosages were
      assayed 5 h after surgery. Liver mitochondria were isolated for in vitro
      functional characterization, including mitochondrial respiratory parameters,
      oxidative phosphorylation efficiency, oxi-radical production, membrane potential,
      and cytochrome c oxidase activity and content. Liver interleukin 1beta (IL-1beta)
      and tumor necrosis alpha mRNA levels were determined. Septic shock induced a
      severe hypotension occurring 180 min after CLP in association with a metabolic
      acidosis, an increase in plasma alanine amino transferase, liver IL-1beta gene
      expression, and mitochondrial reactive oxygen species production. The rates of
      mitochondrial oxygen consumption and the activity and content of cytochrome c
      oxidase were significantly decreased while no alterations in the oxidative
      phosphorylation efficiency and inner membrane integrity were found. These results
      show that contrary to what was expected, liver mitochondria felt to adjust their
      oxidative phosphorylation efficiency in response to the decrease in the
      mitochondrial oxidative activity induced by CLP. This loss of mitochondrial
      bioenergetics plasticity might be related to mitochondrial oxidative stress and
      liver cytokines production. 

PMID- 24570094
TI  - Metabolic tumour volumes measured at staging in lymphoma: methodological
      evaluation on phantom experiments and patients.
AB  - PURPOSE: The presence of a bulky tumour at staging on CT is an independent
      prognostic factor in malignant lymphomas. However, its prognostic value is
      limited in diffuse disease. Total metabolic tumour volume (TMTV) determined on
      (18)F-FDG PET/CT could give a better evaluation of the total tumour burden and
      may help patient stratification. Different methods of TMTV measurement
      established in phantoms simulating lymphoma tumours were investigated and
      validated in 40 patients with Hodgkin lymphoma and diffuse large B-cell lymphoma.
      METHODS: Data were processed by two nuclear medicine physicians in Reggio Emilia
      and Creteil. Nineteen phantoms filled with (18)F-saline were scanned; these
      comprised spherical or irregular volumes from 0.5 to 650 cm(3) with tumour-to
      background ratios from 1.65 to 40. Volumes were measured with different SUVmax
      thresholds. In patients, TMTV was measured on PET at staging by two methods:
      volumes of individual lesions were measured using a fixed 41% SUVmax threshold
      (TMTV41) and a variable visually adjusted SUVmax threshold (TMTVvar). RESULTS: In
      phantoms, the 41% threshold gave the best concordance between measured and actual
      volumes. Interobserver agreement was almost perfect. In patients, the agreement
      between the reviewers for TMTV41 measurement was substantial (rho c = 0.986, CI
      0.97 - 0.99) and the difference between the means was not significant (212 +/-
      218 cm(3) for Creteil vs. 206 +/- 219 cm(3) for Reggio Emilia, P = 0.65). By
      contrast the agreement was poor for TMTVvar. There was a significant direct
      correlation between TMTV41 and normalized LDH (r = 0.652, CI 0.42 - 0.8, P
      <0.001). Higher disease stages and bulky tumour were associated with higher
      TMTV41, but high TMTV41 could be found in patients with stage 1/2 or nonbulky
      tumour. CONCLUSION: Measurement of baseline TMTV in lymphoma using a fixed 41%
      SUVmax threshold is reproducible and correlates with the other parameters for
      tumour mass evaluation. It should be evaluated in prospective studies.

PMID- 24570095
TI  - Characterizing bone marrow involvement in Hodgkin's lymphoma by FDG-PET/CT.
AB  - PURPOSE: Fluoro-deoxyglucose positron emmission tomography combined with computed
      tomography (FDG-PET/CT) is superior to iliac bone marrow biopsy (iBMB) for
      detection of bone marrow involvement (BMI) in staging of Hodgkin's lymphoma (HL).
      The present study aims to characterize the patterns and distribution of BMI in HL
      as determined by FDG-PET/CT. METHODS: Reports of FDG-PET/CT studies performed for
      staging of HL were reviewed. BMI was defined as positive iBMB and/or foci of
      pathological FDG uptake in the skeleton that behaved in concordance with other
      sites of lymphoma in studies following chemotherapy. Number of FDG uptake foci,
      their specific location in the skeleton and the presence of corresponding lesions
      in the CT component of the study, and stage according to the Ann Arbor staging
      system, were recorded. RESULTS: The study included 473 patients. iBMB was
      performed in 336 patients. Nine patients had positive iBMB (9/336, 3%). Seventy
      three patients (73/473, 15%) had FDG-PET/CT-defined BMI. The BM was the only
      extranodal site of HL in 52/473 patients (11 %). Forty-five patients had three or
      more foci of pathological skeletal FDG uptake (45/73, 62 %). Sixty-four patients
      (64/73, 88%) had at least one uptake focus in the pelvis or vertebrae. In 60
      patients (60/73, 82%), the number of skeletal FDG uptake foci without
      corresponding CT lesions was equal to or higher than the number of foci with
      morphological abnormalities. CONCLUSION: FDG-PET/CT demonstrated BMI in 15% of
      patients with newly diagnosed HL. Diagnosis of BMI in HL by FDG-PET/CT was more
      sensitive than iBMB with potential upstage in 11% of patients. The most common
      pattern of FDG-PET/CT BMI was multifocal (at least three foci) skeletal FDG
      uptake, with at least one focus in the pelvis or vertebrae and no corresponding
      CT lesions.

PMID- 24570096
TI  - (177)Lu-DOTATATE therapy in patients with neuroendocrine tumours: 5 years'
      experience from a tertiary cancer care centre in India.
AB  - PURPOSE: The choice of an appropriate treatment option in patients with
      inoperable or metastatic neuroendocrine tumours (NETs) is limited, and
      approximately 50 % of patients have advanced NET at diagnosis, and 65 % die
      within 5 years. Treatment with (177)Lu-DOTATATE ((177)Lu-[DOTA(0),Tyr(3)]
      octreotate) is a promising new option in the treatment of metastatic NETs.
      METHODS: Patients with metastatic NET who underwent (177)Lu-DOTATATE during the
      period 2009 to 2013 were included in this retrospective study. Follow-up imaging
      studies including a (68)Ga-DOTANOC PET/CT scan and a posttherapy (177)Lu-DOTATATE
      scan were compared with baseline imaging to determine response to treatment.
      Progression-free survival (PFS) was calculated using the Kaplan-Meier method and
      Cox regression analysis was also done. RESULTS: Ten patients (25 %) had a minimal
      response, 13 (32.5 %) had a partial response and 9 (22.5 %) had stable disease.
      Progressive disease was seen in 8 patients (20 %), including 6 patients who died
      during or after the treatment period. The estimated mean PFS in those who
      received one or two cycles of (177)Lu-DOTATATE was 8.3 months (95 % CI 6.2 to
      10.3 months) compared to an estimated mean PFS of 45.6 months (95 % CI 40.9 to
      50.2 months) in those who received more than two cycles of (177)Lu-DOTATATE (log
      rank Mantel-Cox Chi (2) = 8.01, p = 0.005). CONCLUSION: Our study showed that
      treatment with (177)Lu-DOTATATE should be considered in the management of NETs,
      considering the limited success of alternative treatment modalities. Treatment
      response and PFS is determined primarily by the dose delivered and best results
      are obtained when more than two cycles of (177)Lu-DOTATATE are given, with
      careful monitoring for possible side effects.

PMID- 24570098
TI  - Smoking-related thoughts and microbehaviours, and their predictive power for
      quitting.
AB  - BACKGROUND: Negative attitudes to smoking are well-established predictors of
      intentions to quit and quit behaviours, but less attention has been given to
      whether quitting is influenced by smoking-related thoughts and microbehaviours
      that reflect a concern about smoking. OBJECTIVES: This paper aimed to describe
      the occurrence of smoking-related thoughts and microbehaviours among Chinese
      smokers, and to examine their predictive power for making quit attempts and
      sustained abstinence. METHODS: The data came from the first three waves of the
      International Tobacco Control China Survey. Four measures of recent thoughts
      about smoking and two microbehaviour measures (collectively referred to as
      microindicators) were examined. RESULTS: Most smokers (around three-quarters)
      reported thinking about harms of smoking to themselves or to others at least
      occasionally, and an increasing minority reported the two microbehaviours of
      prematurely butting out cigarettes and forgoing them. All microindicators were
      positively related to subsequent quit attempts in individual predictor analyses,
      but only serious thoughts about quitting and butting out cigarettes had
      independent relationships. Overall, there was no clear relationship between these
      microindicators and sustained abstinence. CONCLUSIONS: There was a moderately
      high level of occurrence of recent smoking-related thoughts and microbehaviours
      among the Chinese adult smokers in the six cities studied. Like in the West,
      microindicators of concern about smoking were positively associated with
      subsequent quit attempts, but unlike in the West, they were largely unrelated to
      sustained abstinence.

PMID- 24570099
TI  - State-level tobacco environments and sexual orientation disparities in tobacco
      use and dependence in the USA.
AB  - OBJECTIVE: To describe relationships between tobacco-related environments and
      disparities in smoking by sexual orientation. METHODS: We examined three aspects
      of state-level tobacco environments, which were derived from the ImpacTeen State
      Level Tobacco Control Policy and Prevalence Database: (1) tobacco price and tax
      data and tobacco control funding; (2) tobacco control policies and (3) tobacco
      prevalence and norms data. This information was linked to individual-level data
      on sexual orientation, tobacco use and nicotine dependence in Wave 2 of the
      National Epidemiologic Survey on Alcohol and Related Conditions (N=34 653; 577
      LGB respondents), a cross-sectional, nationally representative survey of adults
      in the USA. RESULTS: Lesbian, gay and bisexual (LGB) adults in states with more
      restrictive tobacco environments were less likely to have ever smoked (AOR=0.78,
      95% CI 0.62 to 1.00) and to currently smoke (AOR=0.77, 95% CI 0.60 to 0.99) than
      LGB adults in more permissive tobacco environments. Further, sexual orientation
      disparities in past and current smoking, as well as in current nicotine
      dependence, were lower in states with the most restrictive tobacco environments.
      Results were robust to adjustment for confounders at the individual and state
      levels. CONCLUSIONS: Restrictive state-level tobacco environments are correlates
      of smoking behaviours among LGB adults in the USA; such environments could
      potentially reduce social inequalities in smoking based on sexual orientation.

PMID- 24570097
TI  - A prospective clinical study of 18F-FAZA PET-CT hypoxia imaging in head and neck
      squamous cell carcinoma before and during radiation therapy.
AB  - PURPOSE: Hypoxia in head and neck squamous cell carcinoma (HNSCC) is associated
      with poor prognosis and outcome. (18) F-Fluoroazomycin arabinoside (FAZA) is a
      positron emission tomography (PET) tracer developed to enable identification of
      hypoxic regions within tumor. The aim of this study was to evaluate the use of
      (18) F-FAZA-PET for assessment of hypoxia before and during radiation therapy.
      METHODS: Twelve patients with locally advanced HNSCC underwent (18) F-FAZA-PET
      scans before and at fraction 7 and 17 of concomitant chemo-radiotherapy. A
      hypoxic voxel was defined as a voxel expressing a standardized uptake value (SUV)
      equal or above the SUVmean of the posterior contralateral neck muscles plus three
      standard deviations. The fractional hypoxic volume fraction (FHV) and the spatial
      move of hypoxic volumes during treatment were analyzed. RESULTS: A hypoxic volume
      could be identified in ten patients before treatment. FAZA-PET FHV varied from 0
      to 54.3% and from 0 to 41.4% in the primary tumor and in the involved node,
      respectively. Six out of these ten patients completed all the FAZA-PET-computed
      tomography (CT) during the radiotherapy. In all patients, FHV and SUVmax values
      decreased. All patient presented a spatial move of hypoxic volume, but only three
      patients had newborn hypoxic voxels after 17 fractions. CONCLUSION: This study
      indicated that (18) F-FAZA-PET could be used to identify and quantify tumor
      hypoxia before and during concomitant radio-chemotherapy in patients with locally
      advanced HNSCC. In addition to the information on prognostic value, the use of
      (18) F-FAZA-PET allowed the delineation of hypoxic volumes for dose escalation
      protocols. However, due to fluctuation of hypoxia during treatment, repeated scan
      will have to be performed (i.e. adaptive radiotherapy).

PMID- 24570100
TI  - Snus use and rejection in the USA.
AB  - OBJECTIVE: To determine whether snus might become a strategy for reducing the
      harm associated with cigarette smoking in the USA as appears to be the case in
      Sweden, we examined receptivity to snus use in two cities with the greatest
      exposure to the major brands. METHODS: A dual frame, telephone survey and a brief
      mail survey were conducted in 2011 and 2012 in Indianapolis, Indiana and
      Dallas/Fort Worth Texas. Over 5000 adults completed surveys. Trial, ever use,
      current use and reasons for using or quitting snus after trial were measured.
      RESULTS: Among male smokers, 29.9% had ever tried snus (CI 22.7 to 38.1) and 4.2%
      were current users (CI 1.6 to 10.7). Among female smokers, 8.5% ever tried snus
      (CI 4.4 to 15.7) and current use was unknown. Current use was virtually absent
      among former smokers and never smokers. A major predictor of any level of snus
      use was current use of conventional smokeless tobacco. Those who tried and gave
      up snus cited curiosity (41.3%) and the fact that it was available at low or no
      cost (30%) as reasons for trial; reasons for not continuing included preferring
      another form of tobacco (75.1%) and disliking the mouth feel (34.6%). Almost all
      current snus users indicated that they were trying to cut down on cigarettes, but
      few (3.9%) were using it to quit smoking entirely. CONCLUSIONS: The low rate of
      adoption of snus suggests that neither the hopes nor the fears surrounding this
      new product are likely to be realised in the USA with the current marketing
      patterns.

PMID- 24570101
TI  - Tobacco retail outlet advertising practices and proximity to schools, parks and
      public housing affect Synar underage sales violations in Washington, DC.
AB  - OBJECTIVE: To examine the cross-sectional association between illicit sales of
      tobacco to minors, Washington DC tobacco outlet advertising practices, retail
      store type, the demographic make-up of the area surrounding each outlet, and the
      proximity of each outlet to high schools, recreational parks and public housing.
      PARTICIPANTS: Seven hundred and fifty tobacco outlets in the DC area, n=347 of
      which were randomly selected for inspection by the Synar Inspection Program in
      2009-2010. MAIN OUTCOME MEASURES: The presence of tobacco advertisements on the
      interior and exterior of each outlet, and illicit tobacco sales to Synar
      Inspection Program youth volunteers. RESULTS: The presence of tobacco
      advertisements on the exterior of gas stations was much greater than on other
      retail store types (OR=6.68; 95% CI 4.05 to 11.01), as was the absence of any
      advertisements at bars or restaurants that sold tobacco (OR=0.33; 95% CI 0.22 to
      0.52). Exterior tobacco advertisements were also more likely in predominantly
      African-American areas of the city (OR=3.11; 95% CI 2.28 to 4.25), and
      particularly likely on storefronts located closer to parks (OR=1.87; 95% CI 1.06
      to 3.28). Illicit sales to minors were more common at gas stations (OR=3.01; 95%
      CI 1.5 to 6.3), outlets that displayed exterior tobacco advertisements closer to
      parks (OR=3.36; 95% CI 1.38 to 8.21), and outlets located closer to high schools
      in majority African-American block groups (OR=1.29; 95% CI 1.07 to 1.58).
      CONCLUSIONS: Findings demonstrate that while illicit tobacco sales to minors are
      occurring at acceptably low rates by Synar standards, illicit sales vary
      considerably by retail store type, advertising approach and proximity to high
      schools, parks and African-American residential areas. Future work may help
      inform regulatory efforts to reduce youth access at the neighbourhood, city,
      state and national levels.

PMID- 24570102
TI  - Smoking and long-term labour market outcomes.
AB  - OBJECTIVE: To examine the long-term effects of smoking on labour market outcomes
      using twin data matched to register-based individual information on earnings.
      METHOD: Twin data for Finnish men born 1945-1957 was used to remove the shared
      environmental and genetic factors. The results were subjected to extensive
      robustness testing. Lifetime cigarette consumption was measured by (cumulative)
      cigarette pack-years in early adulthood. The average of an individual's earnings
      (and, alternatively, taxable income) was measured over a subsequent 15-year
      period in later adulthood. RESULTS: Smokers have lower long-term income and
      earnings. For example, controlling for the shared environmental and genetic
      factors using the data on genetically identical twins, smoking is negatively
      associated with lifetime income (p=0.015). The negative association was also
      robust to the use of various covariates, such as education, health indicators and
      extraversion. CONCLUSIONS: Smoking is negatively related to long-term labour
      market outcomes. The provision of information about the indirect monetary costs
      of smoking may thus complement the policy efforts that aim at educating consumers
      about the health costs of smoking.

PMID- 24570104
TI  - Osteonecrosis of the jaw (ONJ) in renal cell cancer patients after treatment
      including zoledronic acid or denosumab.

PMID- 24570103
TI  - Adherence to antiemetic guidelines in patients with malignant glioma: a quality
      improvement project to translate evidence into practice.
AB  - PURPOSE: A quality improvement project was implemented to improve adherence to
      evidence-based antiemetic guidelines for malignant glioma patients treated with
      moderately emetic chemotherapy (MEC). Poorly controlled chemotherapy-induced
      nausea and vomiting (CINV) reduce cancer treatment efficacy and significantly
      impair cancer patients' quality of life (QOL). A review of Duke University
      Preston Robert Tisch Brain Tumor Center (PRTBTC)'s usual practice demonstrates a
      high incidence (45%) of CINV, despite premedication with short-acting 5-HT3
      serotonin-receptor antagonists (5-HT3-RAs). National Comprehensive Cancer Network
      (NCCN)'s evidence-based guidelines recommend the combination of the long-acting 5
      HT3-RA palonosetron (PAL) and dexamethasone (DEX) for the prevention of acute and
      delayed CINV with MEC. Low adherence (58%) to antiemetic guidelines may have
      explained our high CINV incidence. METHODS: One-sample binomial test, quasi
      experimental design, evaluated a combination intervention that included a
      provider education session; implementation of risk-assessment tool with
      computerized, standardized antiemetic guideline order sets; and a monthly audit
      feedback strategy. Post-implementation adherence to evidence-based antiemetic
      order sets and patient outcomes were measured and compared to baseline and
      historical data. Primary outcome was the guideline order set adherence rate.
      Secondary outcomes included nausea/vomiting rates and QOL. RESULTS: Adherence to
      ordering MEC guideline antiemetics increased significantly, from 58% to a
      sustained 90%, with associated improvement in nausea/vomiting. In acute and
      delayed phases, 75 and 84% of patients, respectively, did not experience CINV.
      There was no significant change in QOL. CONCLUSION: Combination intervention and
      audit-feedback strategy to translate evidence into oncology practice improved and
      sustained adherence to antiemetic guidelines. Adherence corresponded with
      effective nausea/vomiting control and preserved QOL in patients with malignant
      gliomas.

PMID- 24570106
TI  - The Mortality Peer Review Panel: a report on the deaths on operations of UK
      Service personnel 2002-2013.
AB  - INTRODUCTION: Review of adverse outcomes is an essential element of healthcare
      governance. For each operational death, the post-mortem is attended by a member
      of Academic Department of Military Emergency Medicine and the case is assessed by
      a Mortality Peer Review Panel comprised of Defence Professors and other clinical
      and technical experts. METHODS: A search was conducted of the Joint Theatre
      Trauma Registry (JTTR) for all UK military death reviews held from January 2002
      to November 2013 and the judgement made by the Mortality Peer Review panel. Cases
      are awarded a 'salvageability' rating between S1 (salvageable) and S4 (not
      salvageable). Cases graded S1-3 are then assessed further for tactical, clinical
      or equipment factors that affected the outcome. RESULTS: There were 621 deaths
      recorded on the JTTR and 517 (83.3%) were due to hostile action. The Killed in
      Action to Died of Wounds ratio is 6.28 : 1. Explosive mechanisms of injury were
      responsible for 55.65% of combat deaths and penetrating mechanisms 28.71%. An
      average of 10.56 injuries was recorded per casualty and the mean number of body
      regions affected was 3.34. The Peer Review Panel decided that 91.1% cases were
      not salvageable (S4); this figure is 93.5% if the deaths due to hostile action
      are considered separately. CONCLUSIONS: The severity of modern military trauma is
      overwhelming in nature and, along with trauma scoring systems, clinical peer
      review is an essential part of healthcare governance. The process also helps
      inform and direct research within clinical and force protection fields.

PMID- 24570105
TI  - Hospice shared-care saved medical expenditure and reduced the likelihood of
      intensive medical utilization among advanced cancer patients in Taiwan--a
      nationwide survey.
AB  - PURPOSE: Hospice shared care (HSC) is a new care model that has been adopted to
      treat inpatient advanced cancer patients in Taiwan since 2005. Our aim was to
      assess the effect of HSC on medical expenditure and the likelihood of intensive
      medical utilization by advanced cancer patients. METHODS: This is a nationwide
      retrospective study. HSC was defined as using "Hospice palliative care (HPC)
      teams to provide consultation and service to advanced cancer patients admitted in
      the nonhospice care ward." There were 120,481 deaths due to cancer between 2006
      and 2008 in Taiwan. Patients receiving HSC were matched by propensity score to
      patients receiving usual care. Of the 120,481 cancer deaths, 12,137 paired
      subjects were matched. Medical expenditures for 1 year before death were assessed
      between groups using a database from the Bureau of National Health Insurance.
      Paired t and McNemar's tests were applied for comparing the medical expenditure
      and intensive medical utilization before death between paired groups. RESULTS:
      Compared to the non-HSC group, subjects receiving HSC had a lower average medical
      expenditure per person (US$3,939 vs. US$4,664; p<0.001). The HSC group had an
      adjusted net savings of US$557 (13.3%; p<0.001) in inpatient medical expenditure
      per person compared with the non-HSC group. Subjects that received different
      types of HPC had 15.4-44.9% less average medical expenditure per person and
      significantly lower likelihood of intensive medical utilization than those that
      did not receive HPC. CONCLUSIONS: HSC is associated with significant medical
      expenditure savings and reduced likelihood of intensive medical utilization. All
      types of HPC are associated with medical expenditure savings.

PMID- 24570107
TI  - [Elastography as an additional tool in breast sonography. Technical principles
      and clinical applications].
AB  - In recent years the use of elastography in addition to sonography has become a
      routine clinical tool for the characterization of breast masses. Whereas free
      hand compression elastography results in qualitative imaging of tissue stiffness
      due to induced compression, shear wave elastography displays quantitative
      information of tissue displacement. Recent studies have investigated the use of
      elastography in addition to sonography and improvement of specificity in
      differentiating benign from malignant breast masses could be shown. Therefore,
      additional use of elastography could help to reduce the number of unnecessary
      biopsies in benign breast lesions especially in category IV lesions of the
      ultrasound breast imaging reporting data system (US-BI-RADS). 

PMID- 24570108
TI  - [Future of mammography-based imaging].
AB  - Mammography is the central diagnostic method for clinical diagnostics of breast
      cancer and the breast cancer screening program. In the clinical routine
      complementary methods, such as ultrasound, tomosynthesis and optional magnetic
      resonance imaging (MRI) are already combined for the diagnostic procedure. Future
      developments will utilize investigative procedures either as a hybrid
      (combination of several different imaging modalities in one instrument) or as a
      fusion method (the technical fusion of two or more of these methods) to implement
      fusion imaging into diagnostic algorithms. For screening there are reasonable
      hypotheses to aim for studies that individualize the diagnostic process within
      the screening procedure. Individual breast cancer risk prediction and
      individualized knowledge about sensitivity and specificity for certain diagnostic
      methods could be tested. The clinical implementation of these algorithms is not
      yet in sight. 

PMID- 24570109
TI  - [Diffusion-weighted breast imaging. Clinical implementation procedure].
AB  - Diffusion-weighted imaging (DWI) of the breast provides additional contrast
      information in breast magnetic resonance imaging (MRI). The DWI procedure can
      easily be implemented in the routine breast MRI protocol with little time
      expenditure regarding image acquisition and evaluation. Evaluation of the DW
      images can be performed with or without the routine breast MRI sequences (T2w and
      T1w with contrast material) but evaluation in combination with the routine
      program is highly recommended. Objective analysis of the tissue diffusion can be
      achieved by calculating the apparent diffusion coefficient (ADC) value with the
      scanner software. The choice of the DW sequence, evaluation and determination of
      the ADC threshold to differentiate between benign and malignant lesions should be
      scanner adapted. The use of DW imaging qualifies for routine use regarding the
      differentiation between malignant and benign breast lesions. Non-mass-like
      lesions and monitoring neoadjuvant chemotherapy can also be evaluated with DW
      sequences. The benefit of the additional information from DW-MR mammography to
      characterize non-mass-like lesions and in the course of neoadjuvant chemotherapy
      remains unclear to date. 

PMID- 24570110
TI  - [Imaging of the elbow joint with focus MRI. Part 2: muscles, nerves and synovial
      membranes].
AB  - This review article discusses the magnetic resonance imaging (MRI) features and
      pathological changes of muscles, nerves and the synovial lining of the elbow
      joint. Typical imaging findings are illustrated and discussed. In addition, the
      cross-sectional anatomy and anatomical variants, such as accessory muscles and
      plicae are discussed. Injuries of the muscles surrounding the elbow joint, as
      well as chronic irritation are particularly common in athletes. Morphological
      changes in MRI, for example tennis or golfer's elbow are typical and often
      groundbreaking. By adapting the examination sequences, imaging planes and slices,
      complete and incomplete tendon ruptures can be reliably diagnosed. Although the
      clinical and electrophysiological examinations form the basis for the diagnosis
      of peripheral neuropathies, MRI provides useful additional information about the
      precise localization due to its high resolution and good soft tissue contrast and
      helps to rule out differential diagnoses. Synovial diseases, such as inflammatory
      arthritis, proliferative diseases and also impinging plicae must be considered in
      the MRI diagnostics of the elbow joint. 

PMID- 24570111
TI  - Spatiotemporal pattern of RNA-binding motif protein 3 expression after spinal
      cord injury in rats.
AB  - RNA-binding motif protein 3 (RBM3) belongs to a very small group of cold
      inducible proteins with anti-apoptotic and proliferative functions. To elucidate
      the expression and possible function of RBM3 in central nervous system (CNS)
      lesion and repair, we performed a spinal cord injury (SCI) model in adult rats.
      Western blot analysis revealed that RBM3 level significantly increased at 1 day
      after damage, and then declined during the following days. Immunohistochemistry
      further confirmed that RBM3 immunoactivity was expressed at low levels in gray
      and white matters in normal condition and increased at 1 day after SCI. Besides,
      double immunofluorescence staining showed RBM3 was primarily expressed in the
      neurons and a few of astrocytes in the normal group. While after injury, the
      expression of RBM3 increased both in neurons and astrocytes at 1 day. We also
      examined the expression profiles of proliferating cell nuclear antigen (PCNA) and
      active caspase-3 in injured spinal cords by western blot. Importantly, double
      immunofluorescence staining revealed that cell proliferation evaluated by PCNA
      appeared in many RBM3-expressing cells and rare caspase-3 was observed in RBM3
      expressing cells at 1 day after injury. Our data suggested that RBM3 might play
      important roles in CNS pathophysiology after SCI.

PMID- 24570112
TI  - Piracetam ameliorated oxygen and glucose deprivation-induced injury in rat
      cortical neurons via inhibition of oxidative stress, excitatory amino acids
      release and P53/Bax.
AB  - Our previous work has demonstrated that piracetam inhibited the decrease in amino
      acid content induced by chronic hypoperfusion, ameliorated the dysfunction of
      learning and memory in a hypoperfusion rat model, down-regulated P53, and BAX
      protein, facilitated the synaptic plasticity, and may be helpful in the treatment
      of vascular dementia. To explore the precise mechanism, the present study further
      evaluated effects of piracetam on Oxygen and glucose deprivation (OGD)-induced
      neuronal damage in rat primary cortical cells. The addition of piracetam to the
      cultured cells 12 h before OGD for 4 h significantly reduced neuronal damage as
      determined by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide)
      assay and lactate dehydrogenase release experiments. Piracetam also lowered the
      levels of malondialdehyde, nitrogen monoxidum, and xanthine oxidase which was
      increased in the OGD cells, and enhanced the activities of superoxide dismutase
      and glutathione peroxidase, which were decreased in the OGD cells. We also
      demonstrated that piracetam could decrease glutamate and aspartate release when
      cortical cells were subjected to OGD. Furthermore, Western blot study
      demonstrated that piracetam attenuated the increased expression of P53 and BAX
      protein in OGD cells. These observations demonstrated that piracetam reduced OGD
      induced neuronal damage by inhibiting the oxidative stress and decreasing
      excitatory amino acids release and lowering P53/Bax protein expression in OGD
      cells.

PMID- 24570114
TI  - First-line beta-blockers versus other antihypertensive medications for chronic
      type B aortic dissection.
AB  - BACKGROUND: Thoracic aortic dissection (TAD) is a severe and often lethal
      complication in people with hypertension. Current practice in the treatment of
      chronic type B aortic dissections is the use of beta-blockers as first-line
      therapy to decrease aortic wall stress. Other antihypertensive medications, such
      as calcium channel blockers (CCBs), angiotensin-converting enzyme (ACE)
      inhibitors or angiotensin II receptor blockers (ARBs), have been suggested for
      the medical therapy of type B TAD. OBJECTIVES: To assess the effects of first
      line beta-blockers compared with other first-line antihypertensive drug classes
      for treating chronic type B TAD. SEARCH METHODS: We searched the Database of
      Abstracts of Reviews of Effects (DARE) for related reviews. We searched the
      Hypertension Group Specialised Register (1946 to 26 January 2014), the Cochrane
      Central Register of Controlled Trials (2014, Issue 1), MEDLINE (1946 to 24
      January 2014), MEDLINE In-Process, EMBASE (1974 to 24 January 2014) and
      ClinicalTrials.gov (to 26 January 2014). SELECTION CRITERIA: We considered
      randomized controlled trials (RCTs) comparing different antihypertensive
      medications in the treatment of chronic type B TAD to be eligible for inclusion.
      Total mortality rate was the primary outcome of this review. Secondary outcomes
      included total non-fatal adverse events relating to TADs and number of people not
      requiring surgical treatment. DATA COLLECTION AND ANALYSIS: Two review authors
      (KC, PL) independently reviewed titles and abstracts and decided on studies to
      include based on the inclusion criteria. We resolved discrepancies between the
      two review authors by discussion. MAIN RESULTS: After a thorough review of the
      search results, we identified no studies that met the inclusion criteria.
      AUTHORS' CONCLUSIONS: We did not find any RCTs that compared first-line beta
      blockers with other first-line antihypertensive medications for the treatment of
      chronic type B TAD. Therefore, there is no RCT evidence to support the current
      guidelines recommending the use of beta-blockers. RCTs are required to assess the
      benefits and harms of beta-blockers and other antihypertensive medications as
      first-line treatment of chronic type B TAD.

PMID- 24570113
TI  - Isoproterenol induced stressful reactions in the brain are characterized by
      inflammation due to activation of NADPH oxidase and ER stress: attenuated by
      Apocynin, Rehmannia complex and Triterpene acids.
AB  - Inflammatory changes in the cerebral network are present in early mechanisms
      involved in neurodegenerative disease, Alzheimer disease (AD), and aging brain.
      We intended to verify that these are likely due to an activation of NADPH oxidase
      (NOX) and endoplasmic reticulum (ER) stress. Apocynin (APO) an inhibitor of NOX
      is potential to ameliorate these changes. Rehmannia complex (Reh) a famous
      prescription in China and the triterpene acids (TTA) isolated from Reh may
      relieve the isoproterenol (ISO) induced chronic inflammation in the brain,
      compared with APO. Rats were administered with ISO for 10 days and astrocytes
      were incubated with ISO for 24 h. Changes in neural MMP (matrix
      metalloproteinase), Cx43, AQP4 (aquaporin 4), NFkappaB, IkappaBbeta, and p-PERK
      (PKB like kinase) were conducted and intervened with APO, Reh and TTA, in vivo
      and in vitro, respectively. An increased MDA and upregulated NOX subunit p47phox,
      ETA, PERK in association with abnormal MMP-2/9 and Cx40/43 were found in cerebral
      tissue of ISO-injected rats. Astrocytes incubated with ISO exhibited upregulated
      APQ4, IkappaBbeta, NFkappaB and p-PERK/PERK and downregulated Cx43. These were
      significantly abrogated by APO and Reh, in vivo, and APO and TTA in vitro. In
      conclusion, neural damages induced by ISO were characterized by inflammatory
      changes in cerebral tissue and astrocytes, which were blunted significantly by
      APO, Reh and TTA, respectively. Reh and TTA are potential in alleviating the
      early pathogenesis in neurodegenerative changes in AD in the clinical settings
      through suppressing NOX and ER stress in the brain. 

PMID- 24570116
TI  - [Cryptococcal neuromeningitidis in HIV-infected patients in Bangui, in the era of
      antiretroviral treatment].
AB  - The cryptococcal neuromeningitis is the most common fungal meningitis infections
      in the course of HIV/AIDS. This is the number two of opportunist infection of the
      central nervous system. The authors post the outcomes of a retrospective study
      conducted related to 122 cases of cryptococcal neuromeningitis observed over for
      four years ago, in Bangui in the Central African Republic, this at time when
      antiretroviral treatment has been avaible, corresponding to a prevalence of 6.5%.
      These infections very aften occur more in female folk, and to patients whose
      average age is 35 years old, ranging from 18 to 69 years old. The clinical
      symptoms often found had been headache (98,3.%), fever (95.0%), the impairing of
      the overall condition of the patient (86.7%) and neck stiffness (85.9%). It makes
      sense to notice that comorbidity case alowgwith tuberculosis, intestinal
      candidiasis, bacterial pneumonia and Kaposi's diseases were found out. The
      screening of the cerebrospinal fluid showed a sound cell count and even low count
      in 12.2% of cases. Direct examination of cerebrospinal fluid with India ink helps
      in diagnosis of 97.5% of cases, and the culture carried out from 74 patients was
      in any case positive. This culture allowed the diagnosis of three patients whose
      examination along side with India ink has been negative. The CD4 cell count was
      less than 100/mm(3) in 97.7% of cases. The rate of the fatality cases has been
      66.4%, it has been badly impacted by a CD4 count <50/mm(3) and the lack of
      antiretroviral therapy. Despite the establishment of a national antiretroviral
      treatment program to do influence the frequency of opportunistic infections whose
      cryptococcal neuromeningitis, this condition is still present although it is
      declining. The clinical variability of this disease requires early diagnosis to
      avoid delayed treatment corollary of a very high mortality as we have observed. 

PMID- 24570118
TI  - The Relationships Between Internal and External Threats and Right-Wing Attitudes:
      A Three-Wave Longitudinal Study.
AB  - The interplay between threat and right-wing attitudes has received much research
      attention, but its longitudinal relationship has hardly been investigated. In
      this study, we investigated the longitudinal relationships between internal and
      external threats and right-wing attitudes using a cross-lagged design at three
      different time points in a large nationally representative sample (N = 800). We
      found evidence for bidirectional relationships. Higher levels of external threat
      were related to higher levels of Right-Wing Authoritarianism (RWA) and to both
      the egalitarianism and dominance dimensions of Social Dominance Orientation at a
      later point in time. Conversely, higher levels of RWA were also related to
      increased perception of external threat later in time. Internal threat did not
      yield significant direct or indirect longitudinal relationships with right-wing
      attitudes. Theoretical and practical implications of these longitudinal effects
      are discussed.

PMID- 24570117
TI  - Family tetrodotoxin poisoning in Reunion Island (Southwest Indian Ocean)
      following the consumption of Lagocephalus sceleratus (Pufferfish).
AB  - Pufferfish poisoning has rarely been reported in the southwestern Indian Ocean
      and in the French overseas territories. In Reunion Island, the last notified
      documented case occurred in 1989 and people are no longer aware of the potential
      toxicity of pufferfish. We report a family hospitalized for a tetrodotoxin
      poisoning following the consumption of Lagocephalus sceleratus caught on the
      coast of Reunion Island in September 2013. Two patients presenting acute vital
      functions failures were admitted in an ICU. Ten people were admitted
      simultaneously to the emergency department after consuming L. sceleratus with
      signs of toxicity appearing within 2 hours. Treatment was supportive, but
      included the need for mechanical ventilation for two patients. All those affected
      had complete and uneventful recoveries within a few days. The fish consumed was
      identified as L. sceleratus, a species known to contain tetrodotoxin. The
      diagnosis of tetrodotoxin poisoning was suggested by typical clinical
      manifestations together with the history of very recent consumption of
      tetrodotoxin-containing fish. Tetrodotoxin was later detected at high levels in
      food remnants. To the best of our knowledge, there has been no documented case
      series of tetrodotoxin poisoning reported from Reunion Island for the last 25
      years and from the entire Indian Ocean area since 1998. Pufferfish intoxication
      is one of the most common causes of poisoning among people in coastal regions of
      Asia but it has also recently been reported in areas where it was previously
      unknown, particularly along the Mediterranean shores and in Spain. Public health
      education in French overseas territories and along the Mediterranean shores
      should be adapted to include increased awareness of the danger of consuming
      pufferfish. Health teams must be aware of such clinical presentations.

PMID- 24570119
TI  - "I" Seek Autonomy, "We" Rely on Each Other: Self-Construal and Regulatory Focus
      as Determinants of Autonomy- and Dependency-Oriented Help-Seeking Behavior.
AB  - There are two typical approaches to requesting help: autonomy-oriented help
      seeking (asking in order to learn how to fix a problem) versus dependency
      oriented help-seeking (asking a helper to fix it). This article presents three
      studies demonstrating a systematic impact of a person's chronic or activated self
      construal (interdependent vs. independent) that operates through activated
      regulatory focus (prevention vs. promotion) on these two help-seeking styles. The
      hypothesis was tested by measuring chronic self-construal, regulatory foci, and
      help-seeking styles (Study 3), and by priming self-construal (Study 1) and
      regulatory focus (Study 2). Results show that people with an independent self
      construal and a promotion focus prefer autonomy-oriented help, whereas people
      with an interdependent self-construal and a prevention focus seek dependency
      oriented help. Mediation analysis (Study 3) shows that regulatory focus is a
      mediator between self-construal and help-seeking styles. The conceptual and
      applied implications of these findings are discussed.

PMID- 24570120
TI  - WARM N COLD: malignant and benign renal tumors in children.
AB  - Although Wilms tumor is the most common renal malignancy in children, the
      differential diagnosis is extensive and includes both malignant and benign
      disorders. We present a simple mnemonic-WARM N COLD, to aid in remembering these
      diverse tumors. Imaging clues including age of the patient, associated disease or
      syndrome as well as salient imaging characteristics such as bilaterality, and
      type or presence of metastasis are also presented and can help differentiate
      between these renal tumors of childhood. 

PMID- 24570122
TI  - Anatomical variants and pathologies of the vermix.
AB  - The appendix may demonstrate a perplexing range of normal and abnormal
      appearances on imaging exams. Familiarity with the anatomy and anatomical
      variants of the appendix is helpful in identifying the appendix on ultrasound,
      computed tomography, and magnetic resonance imaging. Knowledge of the variety of
      pathologies afflicting the appendix and of the spectrum of imaging findings may
      be particularly useful to the emergency radiologist for accurate diagnosis and
      appropriate guidance regarding clinical and surgical management. In this
      pictorial essay, we review appendiceal embryology, anatomical variants such as
      Amyand hernias, and pathologies from appendicitis to carcinoid, mucinous, and
      nonmucinous epithelial neoplasms. 

PMID- 24570121
TI  - High-pressure paint gun injury: clinical presentation and imaging findings.
AB  - High-pressure paint gun injuries are potentially devastating injuries that
      require emergent surgical incision and drainage. They result from erroneous
      equipment operation and accidental injection of a variety of substances at
      pressures high enough to breach the skin. The largely benign superficial
      appearance masks the extent of the underlying injury. In the absence of an
      appropriate history, the radiologist must recognize the characteristic
      radiographic findings and suggest the diagnosis to the clinician. 

PMID- 24570123
TI  - The height for screw index (HSI) predicts the development of C2 nerve dysfunction
      associated with C1 lateral mass screw fixation for atlantoaxial instability.
AB  - PURPOSE: To propose a new measure, the height for screw index (HSI), as a
      predictor of C2 nerve dysfunction in patients who have received posterior C1
      lateral mass screw (C1LMS) fixation for atlantoaxial instability and to examine
      whether the HSI scores correlated with the development of C2 nerve dysfunction
      through retrospective analysis of 104 C1LMS inserted in 52 patients with
      atlantoaxial instability. METHODS: The medical records of patients who underwent
      C1LMS fixation were retrospectively reviewed. C1LMS, 3.5 mm in diameter, was
      inserted for atlantoaxial stabilization. The sagittal plane of the planned C1LMS
      trajectory was reconstructed from CT images. The HSI was defined as the
      difference in height between C2 ganglion and its corresponding foramen. C2 nerve
      function was assessed using a validated visual analog scale questionnaire. Each
      foramen receiving C1LMS was considered as a single unit and patients were
      categorized to group 1, HSI >=4.0 mm; group 2, HSI <4.0 mm. RESULTS: The mean HSI
      score was 4.7 +/- 0.8 mm (range 3.1-6.5 mm) with 85 (81.7 %) units in group 1,
      and 19 (18.3 %) units in group 2. Fourteen (13.5 %, 14/104) units developed C2
      nerve dysfunction. C2 nerve dysfunction was reported in 4 units in group 1, and
      10 units in group 2, respectively. The percentage of C2 nerve dysfunction was
      significantly higher in group 2 than that in group 1 (P < 0.001, Pearson Chi
      square test). CONCLUSIONS: The HSI score correlates with the development of C2
      nerve dysfunction in patients receiving C1LMS fixation for atlantoaxial
      instability and may be a useful predictor of C2 nerve dysfunction.

PMID- 24570124
TI  - Do vertebral derotation techniques offer better outcomes compared to traditional
      methods in the surgical treatment of adolescent idiopathic scoliosis?
AB  - PURPOSE: In recent years, authors have described novel derotation techniques for
      surgery in adolescent idiopathic scoliosis. These methods include direct
      vertebral body derotation (DVD) and vertebral coplanar alignment (VCA). By
      improved derotation it is hoped that there is further reduction in rib hump
      prominence and corresponding improvement in patients' quality of life. This paper
      aims to evaluate studies reporting outcomes from DVD and VCA techniques to assess
      if these methods lead to superior radiographic vertebral derotation, rib hump
      correction on surface measurements or patient-reported outcomes compared to
      traditional derotation manoeuvres using similar instrumentation. METHOD:
      Literature review. RESULTS: Fifteen reports were identified. Most comparative
      studies represent class three or four data. DVD and VCA techniques have been
      shown to reduce apical vertebral rotation by 37-63 %. Few studies compare DVD/VCA
      techniques with traditional methods. Most DVD/VCA reports with pedicle screw
      instrumentation have reported superior radiographic derotation on CT compared
      with conventional techniques. Despite this the majority of studies have found
      similar corrections of rib hump measurements between DVD/VCA techniques and
      cantilever or global derotation methods. There is no evidence that DVD/VCA
      techniques allow greater correction of significant rib hump deformity without an
      adjuvant thoracoplasty. No studies to date have used patient-reported outcomes
      prospectively or demonstrated clinically meaningful differences retrospectively
      between DVD/VCA and conventional techniques. CONCLUSIONS: There is little
      evidence to recommend the widespread adoption of DVD/VCA techniques. Whilst there
      is some weak evidence to suggest that novel techniques may improve radiographic
      measures, there is little to suggest that they offer patients improved correction
      of clinical rib hump or quality of life compared to established techniques.
      Further well-designed prospective studies are needed in this area.

PMID- 24570126
TI  - The growth and increase of the number of journals focusing on Spine: a scientific
      blessing?

PMID- 24570125
TI  - Postural control in individuals with and without non-specific chronic low back
      pain: a preliminary case-control study.
AB  - STUDY DESIGN: A preliminary case-control study. OBJECTIVE: To assess postural
      control in individuals with and without non-specific chronic low back pain (cLBP)
      during quiet standing. cLBP affects 12-33 % of the adult population. Reasons for
      pain chronicity are yet poorly known. Change in postural control may be a risk
      factor for cLBP, although available studies are not conclusive. METHODS: Sample
      consisted of 21 individuals with cLBP and 23 controls without cLBP. Balance was
      assessed using a force plate (Balance Master, NeuroCom) by the modified clinical
      test of sensory interaction and balance, pain severity by the visual analogue
      scale, quality of life with the SF-36 Questionnaire, and functional disability
      with the Roland-Morris Questionnaire. RESULTS: Groups were homogeneous for age,
      weight, height and body mass index. Relative to controls, participants in the
      cLBP group had deficits in the postural control, with greater postural sway in
      the quiet standing condition with closed eyes closed on unstable surfaces (p <
      0.05) for the following parameters: total COP oscillation [cLBP 1,432.82 (73.27)
      vs CG 1,187.77 (60.30)], root mean square sagittal plane [cLBP 1.21 (0.06) vs CG
      1.04 (0.04)], COP area [cLBP 24.27 (2.47) vs CG 16.45 (1.79)] and mean speed of
      oscillation [cLBP 12.97 (0.84) vs CG 10.55 (0.70)]. CONCLUSION: Postural control,
      as evidenced by increased oscillation of COP, is impaired in individuals with
      cLBP relative to controls. Differences are magnified by visual deprivation and
      unstable surface conditions.

PMID- 24570127
TI  - Global patterns of apparent copy number variation in birds revealed by cross
      species comparative genomic hybridization.
AB  - There is a growing interest in copy number variation (CNV) and the recognition of
      its importance in phenotype, disease, adaptation and speciation. CNV data is
      usually ascertained by array-CGH within-species, but similar inter-species
      comparisons have also been made in primates, mice and domestic mammals. Here, we
      conducted a broad appraisal of putative cross-species CNVs in birds, 16 species
      in all, using the standard array-CGH approach. Using a chicken oligonucleotide
      microarray, we detected 790 apparent CNVs within 135 unique regions and developed
      a bioinformatic tool 'CNV Analyser' for analysing and visualising cross-species
      data sets. We successfully addressed four hypotheses as follows: (a) Cross
      species CNVs (compared to chicken) are, as suggested from preliminary evidence,
      smaller and fewer in number than in mammals; this 'dogma' was rejected in the
      light of the new evidence. (b) CNVs in birds are likely to have a functional
      effect through an association with genes; a large proportion of detected regions
      (70 %) were indeed associated with genes (suggesting functional significance),
      however, not necessarily more so than in mammals. (c) There are more CNVs in
      birds with more rearranged karyotypes; this hypothesis was rejected. Indeed,
      Falco species contained fewer than most with relatively standard (chicken-like)
      karyotypes. (d) There are more CNVs per megabase on micro-chromosomes than
      macrochromosomes; this hypothesis was accepted. Indeed, in species with
      rearranged karyotypes characterised by chromosomal fusions, the fused former
      microchromosomes still 'behaved' as though they were their microchromosomal
      ancestors. Gene ontology analysis of CNVRs revealed enrichment in immune response
      and antigen presentation genes and five CNVRs were perfectly correlated with the
      unique loss of sexual dichromatism in one Galliformes species. 

PMID- 24570129
TI  - Evaluation of coating properties of enteric-coated tablets using terahertz pulsed
      imaging.
AB  - PURPOSE: Enteric coatings are used to reduce gastrointestinal side effects and
      control the release properties of oral medications. Although widely used, the
      effect of formulation and process conditions on physicochemical and functional
      properties of enteric coatings remains unclear. METHODS: Terahertz pulsed imaging
      (TPI) was employed to evaluate the coat properties of enteric coated tablets
      (ECTs) with various acid resistance. Other analytic methods, such as loss on
      drying, scanning electron microscopy and X-ray computed tomography were then used
      to validate the relationships established among 4 TPI-derived parameters and the
      physicochemical properties of enteric coatings. RESULTS: Weight gain measurement
      did not provide any information to assess acid resistance of enteric coating,
      whereas four TPI-derived parameters non-destructively reflected the coating
      properties such as thickness, coat uniformity, density, and water distribution,
      allowing the identification of the causes of poor acid resistance in certain ECT
      batches using a single measurement. These parameters also revealed the effect of
      coating conditions; in particular, coating under dry conditions led to less dense
      and nonuniform coatings with poor acid resistance. CONCLUSION: We demonstrated
      the utility of TPI to identify structural defects within ECTs with poor acid
      resistance. TPI-derived parameters can aid in formulation development and quality
      control of ECTs.

PMID- 24570131
TI  - Considerations regarding the alleged association between Herbalife products and
      cases of hepatotoxicity: a rebuttal.

PMID- 24570130
TI  - A model for targeting colon carcinoma cells using single-chain variable fragments
      anchored on virus-like particles via glycosyl phosphatidylinositol anchor.
AB  - PURPOSE: VLPs displaying tumor targeting single-chain variable fragments (VLP
      rscFvs) which targets tumor-associated glycoprotein-72 (TAG-72) marker protein
      have a potential for immunotherapy against colon carcinoma tumors. In this study,
      scFvs anchored on VLPs using glycosylphosphatidylinositol (GPI) were prepared to
      target colon carcinoma spheroids in vitro. METHODS: VLPs-rscFvs were produced by
      co-injecting two types of Bombyx mori nucleopolyhedrovirus (BmNPV) bacmids,
      encoding RSV-gag and rscFvs cDNA into silkworm larvae. Large unilamellar vesicles
      (LUVs) of 100 nm in diameter were made using 1,2-dioleoyl-sn-glycero-3
      phosphocholine (DOPC) and packaged with Sulforhodamine B (SRB). LUV-SRB was used
      to associate with VLP-rscFvs assisted by GP64 present on VLP-rscFvs to produce
      VLP-rscFv associated SRB (VLP-rscFvs-SRB) at pH 7.5. RESULTS: The antigenicity of
      the purified VLPs-rScFvs was confirmed by enzyme-linked immunosorbent assay
      (ELISA) using TAG-72 as antigen. LUV-SRB made of DOPC was used to associate with
      100 MUg of VLP-rscFvs to produce VLP-rscFv-SRB. Specific delivery and penetration
      of SRB up to 100 MUm into the spheroids shows the potential of the new model.
      CONCLUSIONS: The current study demonstrated the display, expression and
      purification of VLP-rscFvs efficiently. As a test model VLP-rscFv-SRB were
      prepared which can be used for immunotherapy. rscFvs provide the specificity
      needed to target tumors and VLPs serve as carrier transporting the dye to target.

PMID- 24570132
TI  - Osler's node on the thigh, an uncommon location, but a valuable diagnostic aid.

PMID- 24570134
TI  - [Who will take care of the increasing number of obese? Political action and
      cooperation in health care is needed].

PMID- 24570133
TI  - Rectal cancer in inflammatory bowel diseases: MR imaging findings.
AB  - PURPOSE: To retrospectively analyze the MR imaging features of rectal cancer in
      patients with inflammatory bowel diseases (IBD). MATERIALS AND METHODS: The MR
      imaging examinations of 13 patients with IBD-related rectal cancer were
      retrospectively reviewed. MR imaging included T2-weighted, diffusion-weighted
      (DW), and gadolinium chelate-enhanced MR imaging. MR imaging findings were
      analyzed and compared with endoscopic and histopathological findings. RESULTS:
      Eight patients (8/13; 62%) had active IBD and five (5/13; 38%) had quiescent IBD
      on MR imaging. Two different tumor patterns were individualized including clearly
      visible soft-tissue mass (4/13; 31%) (Type 1 tumor) and marked circumferential
      rectal wall thickening (9/13; 69%) (Type 2 tumor). Twelve tumors (12/13; 92%)
      showed high signal intensity on T2-weighted MR images. All six tumors studied
      with DW-MR imaging (6/6; 100%) showed high signal on DW-MR imaging with
      restricted diffusion on apparent diffusion coefficient (ADC) map. On gadolinium
      chelate-enhanced MR imaging, heterogeneous enhancement was observed in one tumor
      (1/13; 8%), whereas 12 tumors (12/13; 92%) showed homogeneous enhancement. MR
      imaging showed pelvic fistula and intrapelvic abscess in association with four
      (4/13; 31%) and two tumors (2/13; 15%), respectively. CONCLUSION: Our limited
      retrospective study demonstrates that rectal cancer in IBD patients can present
      as a circumferential wall thickening resembling inflammation and can occur in the
      absence of fistula or abscess. The use of T2-weighted and DW-MR imaging is
      recommended to improve rectal cancer detection in patients with long-standing
      IBD.

PMID- 24570135
TI  - [Familial thoracic aortic aneurysms and dissections can be divided into three
      different main categories].
AB  - Thoracic aortic aneurysms and dissections (TAAD) can be divided into three
      different main categories. 1. Inherited syndromes predisposing to TAAD such as
      Marfan syndrome, Ehlers-Danlos syndrome type IV and Loeys-Dietz syndrome (less
      than 5% of all TAAD). 2. Familial TAAD (FTAAD) with more than one affected family
      member (20 % of all TAAD). Inheritance shows an autosomal dominant pattern and
      there are no features of known syndromes. 3. Sporadic forms of TAAD with no
      family history or features of syndromic forms. FTAAD present earlier in life and
      dissections occur in smaller diameter than in sporadic cases. The underlying
      genetic cause can be found in about 20 % of the inherited cases. The pathogenesis
      seems to be an involvement of the transforming growth factor beta (TGFbeta)
      signaling pathway or a dysfunction of the smooth muscle cell contraction. The
      role of beta-blockers for aneurysm prevention is uncertain and there are on-going
      studies comparing angiotensin receptor blockers and beta-blockers. 

PMID- 24570136
TI  - [Vancomycin resistant Staphylococcus epidermidis caused prosthesis infection.
      Linezolid and rifampicin healed the complicated infection].
AB  - Coagulase-negative Staphylococci, including Staphylococcus epidermidis, are
      common pathogens in orthopedic prosthesis infections. Operation and prolonged
      treatment with rifampicin in combination with another antibiotic is often
      required. Coagulase-negative Staph-ylococci are frequently multi-resistant, but
      resistance to vancomycin is rare in Sweden. Linezolid is an alternative, however
      it is only recommended for up to 4 weeks treatment due to risk of hematological
      side effects. We have successfully used prolonged treatment with linezolid and
      rifampicin in a patient suffering from a complicated prosthetic joint infection
      caused by a vancomycin resistant Staphyloccous epidermidis strain. 

PMID- 24570137
TI  - [There are more male than female patients within intensive care. But it is still
      unclear whether there are gender inequalities in Swedish intensive care or not].

PMID- 24570138
TI  - [Early team assessment relieves the emergency department].
AB  - A model for physician-led team triage was evaluated at the Emergency Department
      at the University hospital of Orebro, Sweden. Data from 1600 patients indicate
      that this work model reduces length of stay, time to physician assessment,
      emergency department occupancy, rate of admission and the proportion of patients
      in need of close monitoring. The project was conducted without any change in the
      number of physicians, nurses or staff nurses working in the Emergency Department.

PMID- 24570140
TI  - miR-195 regulates SIRT1-mediated changes in diabetic retinopathy.
AB  - AIMS/HYPOTHESIS: Endothelial cell (EC) damage is a key mechanism causing retinal
      microvascular injury in diabetes. Several microRNAs (miRNAs) have been found to
      regulate sirtuin 1 (SIRT1, which is involved in regulation of the cell cycle,
      survival and metabolism) in various tissues and disease states, but no studies
      have been conducted on the role of miRNA in regulation of SIRT1 in diabetic
      retinopathy. Here we investigated the effect of miRNA-195 (miR-195), a SIRT1
      targeting miRNA, on the development of diabetes-induced changes in ECs and
      retina. METHODS: The level of miR-195 was measured in human retinal and dermal
      microvascular ECs (HRECs, HMECs) following exposure to 25 mmol/l glucose (high
      glucose, HG) and 5 mmol/l glucose (normal glucose, NG). SIRT1 and fibronectin
      levels were examined following transfection with miR-195 mimic or antagomir or
      forced expression of SIRT1. Retinal tissues from diabetic rats were similarly
      studied following intravitreal injection of an miR-195 antagomir or mimic. In
      situ hybridisation was used to localise retinal miR-195. RESULTS: HG caused
      increased miR-195 levels and decreased SIRT1 expression (compared with NG) in
      both HRECs and HMECs. Transfection with miR-195 antagomir and forced expression
      of SIRT1 prevented such changes, whereas transfection with miR-195 mimic produced
      HG-like effects. A luciferase assay confirmed the binding of miR-195 to the 3'
      untranslated region of SIRT1. miR-195 expression was upregulated in retinas of
      diabetic rats and intravitreal injection of miR-195 antagomir ameliorated levels
      of SIRT1. CONCLUSIONS/INTERPRETATION: These studies identified a novel mechanism
      whereby miR-195 regulates SIRT1-mediated tissue damage in diabetic retinopathy.

PMID- 24570142
TI  - Risk factors for complications and in-hospital mortality following hip fractures:
      a study using the National Trauma Data Bank.
AB  - STUDY DESIGN: Retrospective review of prospectively collected data. OBJECTIVE: To
      describe the impact of patient demographics, injury-specific factors, and medical
      co-morbidities on outcomes after hip fracture using the National Sample Program
      (NSP) of the National Trauma Data Bank (NTDB). METHODS: The 2008 NSP-NTDB was
      queried to identify patients sustaining hip fractures. Patient demographics, co
      morbidities, injury-specific factors, and outcomes (including mortality and
      complications) were recorded and a national estimate model was developed.
      Unadjusted differences for risk factors were evaluated using t test/Wald Chi
      square analyses. Weighted logistic regression and sensitivity analyses were
      performed to control for all factors in the model. RESULTS: The weighted sample
      contained 44,419 incidents of hip fracture. The average age was 72.7. Sixty-two
      percent of the population was female and 80 % was white. The mortality rate was
      4.5 % and 12.5 % sustained at least one complication. Seventeen percent of
      patients who sustained at least one complication died. Dialysis, presenting in
      shock, cardiac disease, male sex, and ISS were significant predictors of
      mortality, while dialysis, obesity, cardiac disease, diabetes, and a procedure
      delay of >=2 days influenced complications. The major potential modifiable risk
      factor appears to be time to procedure, which had a significant impact on
      complications. CONCLUSIONS: This is the first study to postulate predictors of
      morbidity and mortality following hip fracture in a US national model. While many
      co-morbidities appear to be influential in predicting outcome, some of the more
      significant factors include the presence of shock, dialysis, obesity, and time to
      surgery. LEVEL OF EVIDENCE: Prognostic study, Level II.

PMID- 24570143
TI  - Operative treatment of displaced Pipkin type I and II femoral head fractures.
AB  - BACKGROUND AND PURPOSE: The optimal surgical approach for the treatment of
      femoral head fracture remains controversial. We retrospectively reviewed patients
      with Pipkin type I and II femoral head fractures managed surgically through
      posterior Kocher-Langenbeck approach and Ganz trochanteric flip approach aiming
      to define the best approach with the least morbidity. PATIENTS AND METHODS:
      Between May 1995 and November 2010, 23 patients (14 men and 9 women) with an
      average age of 39.1 years (range 27-62) were treated by open reduction and
      internal fixation of femoral head fractures (5, Pipkin type I; and 18, type II)
      through Kocher-Langenbeck approach in 11 patients and trochanteric flip
      (digastric) osteotomy in 12. The two approaches were compared regarding operative
      time, difficulty of reduction and fixation, amount of blood loss, occurrence of
      femoral head osteonecrosis or heterotopic ossification and the final functional
      outcome. The scale of Brooker was used to document heterotopic ossification. The
      modified Merle d'Aubigne and Postel as well as Thompson and Epstein scores were
      used for final evaluation. RESULTS: Trochanteric flip approach was associated
      with less operative time, less blood loss and improved visualization facilitating
      direct screw fixation compared with Kocher-Langenbeck approach. Non-union of the
      trochanteric osteotomy developed in one patient. Heterotopic ossification was
      seen more in trochanteric flip-approached cases. Avascular necrosis of the
      femoral head occurred in one patient (8.1 %) of trochanteric flip-approached
      group and two (18.1 %) of posterior approach group. All patients were followed up
      for an average of 31 months (range 24-84). Except for one patient, the final
      outcomes were equal in the two groups. CONCLUSIONS: Despite the limited number of
      patients, we can conclude that good final outcome does not necessarily follow a
      specific approach.

PMID- 24570141
TI  - Young men with low birthweight exhibit decreased plasticity of genome-wide muscle
      DNA methylation by high-fat overfeeding.
AB  - AIMS/HYPOTHESIS: The association between low birthweight (LBW) and risk of
      developing type 2 diabetes may involve epigenetic mechanisms, with skeletal
      muscle being a prime target tissue. Differential DNA methylation patterns have
      been observed in single genes in muscle tissue from type 2 diabetic and LBW
      individuals, and we recently showed multiple DNA methylation changes during short
      term high-fat overfeeding in muscle of healthy people. In a randomised crossover
      study, we analysed genome-wide DNA promoter methylation in skeletal muscle of 17
      young LBW men and 23 matched normal birthweight (NBW) men after a control and a 5
      day high-fat overfeeding diet. METHODS: DNA methylation was measured using
      Illumina's Infinium BeadArray covering 27,578 CpG sites representing 14,475
      different genes. RESULTS: After correction for multiple comparisons, DNA
      methylation levels were found to be similar in the LBW and NBW groups during the
      control diet. Whereas widespread DNA methylation changes were observed in the NBW
      group in response to high-fat overfeeding, only a few methylation changes were
      seen in the LBW group (chi(2), p < 0.001). CONCLUSIONS/INTERPRETATION: Our
      results indicate lower DNA methylation plasticity in skeletal muscle from LBW vs
      NBW men, potentially contributing to understanding the link between LBW and
      increased risk of type 2 diabetes.

PMID- 24570144
TI  - Functional Magnetic Resonance Imaging Study of Apathy in Alzheimer's Disease.
AB  - An fMRI study was launched to understand mechanisms of Alzheimer's disease (AD)
      patients with apathy. The authors reviewed 7 AD patients with apathy and 6 AD
      patients without apathy. The block method was adopted, and 24 pictures
      representing positive, negative, and neutral emotional stimuli were viewed when
      patients were given brain fMRI. Under "sad versus neutral" stimulation, non
      apathetic AD patients had increased activity in bilateral amygdala and bilateral
      fusiform gyrus, whereas apathetic AD patients only had increased activities in
      bilateral fusiform gyrus. Thus, the amygdala was the possible anatomical
      structure related to apathy in AD patients.

PMID- 24570145
TI  - Workplace interventions for smoking cessation.
AB  - BACKGROUND: The workplace has potential as a setting through which large groups
      of people can be reached to encourage smoking cessation. OBJECTIVES: 1. To
      categorize workplace interventions for smoking cessation tested in controlled
      studies and to determine the extent to which they help workers to stop smoking.2.
      To collect and evaluate data on costs and cost effectiveness associated with
      workplace interventions. SEARCH METHODS: We searched the Cochrane Tobacco
      Addiction Group Specialized Register (July 2013), MEDLINE (1966 - July 2013),
      EMBASE (1985 - June 2013), and PsycINFO (to June 2013), amongst others. We
      searched abstracts from international conferences on tobacco and the
      bibliographies of identified studies and reviews for additional references.
      SELECTION CRITERIA: We selected interventions conducted in the workplace to
      promote smoking cessation. We included only randomized and quasi-randomized
      controlled trials allocating individuals, workplaces, or companies to
      intervention or control conditions. DATA COLLECTION AND ANALYSIS: One author
      extracted information relating to the characteristics and content of all kinds of
      interventions, participants, outcomes and methods of the studies, and a second
      author checked them. For this update we have conducted meta-analyses of the main
      interventions, using the generic inverse variance method to generate odds ratios
      and 95% confidence intervals. MAIN RESULTS: We include 57 studies (61
      comparisons) in this updated review. We found 31 studies of workplace
      interventions aimed at individual workers, covering group therapy, individual
      counselling, self-help materials, nicotine replacement therapy, and social
      support, and 30 studies testing interventions applied to the workplace as a
      whole, i.e. environmental cues, incentives, and comprehensive programmes. The
      trials were generally of moderate to high quality, with results that were
      consistent with those found in other settings. Group therapy programmes (odds
      ratio (OR) for cessation 1.71, 95% confidence interval (CI) 1.05 to 2.80; eight
      trials, 1309 participants), individual counselling (OR 1.96, 95% CI 1.51 to 2.54;
      eight trials, 3516 participants), pharmacotherapies (OR 1.98, 95% CI 1.26 to
      3.11; five trials, 1092 participants), and multiple intervention programmes aimed
      mainly or solely at smoking cessation (OR 1.55, 95% CI 1.13 to 2.13; six trials,
      5018 participants) all increased cessation rates in comparison to no treatment or
      minimal intervention controls. Self-help materials were less effective (OR 1.16,
      95% CI 0.74 to 1.82; six trials, 1906 participants), and two relapse prevention
      programmes (484 participants) did not help to sustain long-term abstinence.
      Incentives did not appear to improve the odds of quitting, apart from one study
      which found a sustained positive benefit. There was a lack of evidence that
      comprehensive programmes targeting multiple risk factors reduced the prevalence
      of smoking. AUTHORS' CONCLUSIONS: 1. We found strong evidence that some
      interventions directed towards individual smokers increase the likelihood of
      quitting smoking. These include individual and group counselling, pharmacological
      treatment to overcome nicotine addiction, and multiple interventions targeting
      smoking cessation as the primary or only outcome. All these interventions show
      similar effects whether offered in the workplace or elsewhere. Self-help
      interventions and social support are less effective. Although people taking up
      these interventions are more likely to stop, the absolute numbers who quit are
      low.2. We failed to detect an effect of comprehensive programmes targeting
      multiple risk factors in reducing the prevalence of smoking, although this
      finding was not based on meta-analysed data. 3. There was limited evidence that
      participation in programmes can be increased by competitions and incentives
      organized by the employer, although one trial demonstrated a sustained effect of
      financial rewards for attending a smoking cessation course and for long-term
      quitting. Further research is needed to establish which components of this trial
      contributed to the improvement in success rates.4. Further research would be
      valuable in low-income and developing countries, where high rates of smoking
      prevail and smoke-free legislation is not widely accepted or enforced.

PMID- 24570147
TI  - Ameloblasts express type I collagen during amelogenesis.
AB  - Enamel and enameloid, the highly mineralized tooth-covering tissues in living
      vertebrates, are different in their matrix composition. Enamel, a unique product
      of ameloblasts, principally contains enamel matrix proteins (EMPs), while
      enameloid possesses collagen fibrils and probably receives contributions from
      both odontoblasts and ameloblasts. Here we focused on type I collagen (COL1A1)
      and amelogenin (AMEL) gene expression during enameloid and enamel formation
      throughout ontogeny in the caudate amphibian, Pleurodeles waltl. In this model,
      pre-metamorphic teeth possess enameloid and enamel, while post-metamorphic teeth
      possess enamel only. In first-generation teeth, qPCR and in situ hybridization
      (ISH) on sections revealed that ameloblasts weakly expressed AMEL during late
      stage enameloid formation, while expression strongly increased during enamel
      deposition. Using ISH, we identified COL1A1 transcripts in ameloblasts and
      odontoblasts during enameloid formation. COL1A1 expression in ameloblasts
      gradually decreased and was no longer detected after metamorphosis. The
      transition from enameloid-rich to enamel-rich teeth could be related to a switch
      in ameloblast activity from COL1A1 to AMEL synthesis. P. waltl therefore appears
      to be an appropriate animal model for the study of the processes involved during
      enameloid-to-enamel transition, especially because similar events probably
      occurred in various lineages during vertebrate evolution. 

PMID- 24570146
TI  - Genetic polymorphisms of XRCC1 gene and susceptibility to hepatocellular
      carcinoma in Chinese population.
AB  - Hepatocellular carcinoma (HCC) is a common cancer in the worldwide. Accumulated
      evidences indicate that genetic polymorphisms of human X-ray repair complementing
      group 1 gene (XRCC1) are associated with the susceptibility to HCC. This study
      aims to investigate the potential association between XRCC1 c.482C>T and
      c.1178G>A genetic polymorphisms and the susceptibility to HCC. A total of 1,069
      Chinese Han subjects consisting of 530 HCC patients and 539 cancer-free controls
      were recruited in this case-control study. The created restriction site
      polymerase chain reaction and directly DNA sequencing methods were utilized to
      analyze the genotyping of XRCC1 genetic polymorphisms. Our data suggested that
      the XRCC1 c.482C>T and c.1178G>A genetic polymorphisms were statistically
      associated with the increased risks of HCC [for c.482C>T, TT vs. CC: OR 2.05, 95%
      CI 1.26-3.32, P = 0.003; T vs. C: OR 1.26, 95% CI 1.04-1.51, P = 0.017; for
      c.1178G>A, AA vs. GG: OR 2.15, 95% CI 1.26-3.67, P = 0.004; A vs. G: OR 1.33, 95%
      CI 1.10-1.61, P = 0.004]. The allele-T and genotype-TT of c.482C>T and allele-A
      and genotype-AA of c.1178G>A genetic polymorphisms may enhance the susceptibility
      to HCC. Our findings indicate that the studied XRCC1 genetic polymorphisms may
      influence the risk of HCC in Chinese populations and might be used as molecular
      markers for assessing the risk of HCC.

PMID- 24570148
TI  - Regulatory interplay between NFIC and TGF-beta1 in apical papilla-derived stem
      cells.
AB  - While transforming growth factor-beta1 (TGF-beta1) can regulate odontoblast
      differentiation in tooth crown morphogenesis, its effects on cells including stem
      cells from the apical papilla (SCAPs) involved in root formation are unclear.
      Nuclear factor I-C (NFIC) has been implicated in the regulation of root
      development, and interplay with TGF-beta1 signaling has been reported in some
      cell types. We hypothesize that NFIC and TGF-beta1 are important to the behavior
      of SCAPs and that the interplay between these molecules controls the regulation
      of the odontogenic differentiation of SCAPs. TGF-beta1 inhibited the
      proliferation of SCAPs and their mineralization. Real-time polymerase chain
      reaction (RT-PCR) and Western blot results showed that TGF-beta1 significantly
      decreased osteogenic/dentinogenic gene expression. The inhibition of TGF
      beta/Smad signaling (SIS3) attenuated the suppressive effect of TGF-beta1 on
      SCAPs. Importantly, overexpression of NFIC antagonized the effects of TGF-beta1
      on SCAPs, while knockdown of NFIC enhanced these effects, demonstrating a key
      regulatory role for NFIC in modulating TGF-beta1 signaling in SCAPs. We conclude
      that this interplay between NFIC and TGF-beta1 regulates SCAPs behavior and can
      determine the differentiation of these cells. These signaling interactions help
      inform the development of regenerative strategies aimed at root growth and
      development in immature teeth for endodontic treatment. 

PMID- 24570150
TI  - Fluid structure interaction (FSI) simulation of the left ventricle (LV) during
      the early filling wave (E-wave), diastasis and atrial contraction wave (A-wave).
AB  - In this paper, the hemodynamic characteristics inside a physiologically correct
      three-dimensional LV model using fluid structure interaction scheme are examined
      under various heart beat conditions during early filling wave (E-wave), diastasis
      and atrial contraction wave (A-wave). The time dependent and incompressible
      viscous fluid, nonlinear viscous fluid and the stress tensor equations are
      coupled with the full Navier-Stoke's equations together with the Arbitrary
      Lagrangian-Eulerian and elasticity in the solid domain are used in the analysis.
      The results are discussed in terms of the variation in the intraventricular
      pressure, wall shear stress (WSS) and the fluid flow patterns inside the LV
      model. Moreover, changes in the magnitude of displacements on the LV are also
      observed during diastole period. The results obtained demonstrate that the
      magnitude of the intraventricle pressure is found higher in the basal region of
      the LV during the beginning of the E-wave and A-wave, whereas the Ip is found
      much higher in the apical region when the flow propagation is in peak E-wave,
      peak A-wave and diastasis. The magnitude of the pressure is found to be 5.4E2 Pa
      during the peak E-wave. Additionally, WSS elevates with the rise in the E-wave
      and A-wave but the magnitude decreases during the diastasis phase. During the
      peak E-wave, maximum WSS is found to be 5.7 Pa. Subsequent developments, merging
      and shifting of the vortices are observed throughout the filling wave. Formations
      of clockwise vortices are evident during the peak E-wave and at the onset of the
      A-wave, but counter clockwise vortices are found at the end of the diastasis and
      at the beginning of the A-wave. Moreover, the maximum magnitude of the structural
      displacement is seen in the ventricle apex with the value of 3.7E-5 m.

PMID- 24570149
TI  - Transcriptional factor ATF6 is involved in odontoblastic differentiation.
AB  - ATF6 is an endoplasmic reticulum (ER) membrane-bound transcription factor that
      regulates various cellular functions. The purpose of this study was to
      investigate the role of ATF6 in odontoblast differentiation. Rat tooth germs were
      isolated, changes in gene expression were evaluated over time, and localization
      of ATF6 was determined by immunohistochemistry. Human dental pulp cells (HDPCs)
      were cultured with 50 ug/mL ascorbic acid and 5 mmol/L beta-glycerophosphate or
      100 ng/mL bone morphogenetic protein 2 to induce differentiation. Translocation
      of ATF6 was observed by immunofluorescence and confocal microscopy.
      Overexpression of ATF6 was performed with an adenoviral vector. Matrix
      mineralization was evaluated by alizarin red staining. Immunoreactivity to anti
      ATF6 was observed in the odontoblastic layer of the molar tooth germ, and
      expressions of ATF6, dentin sialophosphoprotein (DSPP) and dentin matrix protein
      1 (DMP1) increased gradually during tooth germ development. When HDPCs were
      cultured in differentiation media, ATF6, DSPP, and DMP1 expression increased with
      the expression of unfolded protein response (UPR) markers, BiP and CHOP.
      Immunofluorescence results showed that ATF6 protein moved from cytoplasm to
      nucleus when cells were exposed to differentiation media. Notably, overexpression
      of ATF6 increased DSPP and DMP1 expression, alkaline phosphatase (ALP) activity,
      and matrix mineralization in HDPC cultures. Inhibition of ATF6 decreased ALP
      activity and mineralization. These results suggest that ER membrane-bound
      transcriptional factor ATF6 may be involved in odontoblastic differentiation. 

PMID- 24570151
TI  - 15-lipoxygenase-mediated modification of HDL3 impairs eNOS activation in human
      endothelial cells.
AB  - Caveolae are cholesterol and glycosphingolipids-enriched microdomains of plasma
      membranes. Caveolin-1 represents the major structural protein of caveolae, that
      also contain receptors and molecules involved in signal transduction pathways.
      Caveolae are particularly abundant in endothelial cells, where they play
      important physiological and pathological roles in regulating endothelial cell
      functions. Several molecules with relevant functions in endothelial cells are
      localized in caveolae, including endothelial nitric oxide synthase (eNOS), which
      regulates the production of nitric oxide, and scavenger receptor class B type I
      (SR-BI), which plays a key role in the induction of eNOS activity mediated by
      high density lipoproteins (HDL). HDL have several atheroprotective functions,
      including a positive effect on endothelial cells, as it is a potent agonist of
      eNOS through the interaction with SR-BI. However, the oxidative modification of
      HDL may impair their protective role. In the present study we evaluated the
      effect of 15-lipoxygenase-mediated modification of HDL3 on the expression and/or
      activity of some proteins localized in endothelial caveolae and involved in the
      nitric oxide generation pathway. We found that after modification, HDL3 failed to
      activate eNOS and to induce NO production, due to both a reduced ability to
      interact with its own receptor SR-BI and to a reduced expression of SR-BI in
      cells exposed to modified HDL. These findings suggest that modification of HDL
      may reduce its endothelial-protective role also by interfering with vasodilatory
      function of HDL. 

PMID- 24570152
TI  - Accuracy of bony landmarks for restoring the natural joint line in revision knee
      surgery: an MRI study.
AB  - PURPOSE: Restoring the joint line (JL) improves clinical and functional outcome
      in total knee arthroplasty (TKA). Therefore, anatomical landmarks to approximate
      the JL have been published. So far, the natural deviation of the JL 90 degrees 
      to the mechanical tibial axis has not been considered. Thus, we designed this
      study to: (1) determine the natural JL of knees in healthy persons in respect to
      the mechanical tibial axis, (2) validate and double-check intra-operative bony
      landmarks already been published in respect to the natural JL and (3) find
      possible correlations between distances from bony landmarks to the JL and femoral
      and tibial width. METHODS: Eighty MRI scans of knees of healthy persons were
      examined by two independent observers. Distances from the tip of the fibular head
      (FH), the medial (ME) and lateral (LE) epicondyles and the adductor tubercle (AT)
      to the JL within the medial and lateral compartment were measured. Further, we
      determined the orientation of the JL in respect to the mechanical axis of the
      tibia. Interobserver correlations were calculated. Differences were analyzed
      using Student's t test. Linear regression models were calculated to analyze
      correlations. RESULTS: Interobserver correlation was excellent. Mean JL deviation
      was 4.2 degrees  varus. Distance between the FH, ME, LE and AT to the JL within
      the medial compartment was 12.2, 33.9, 33.4 and 45.4 mm, respectively. Within in
      the lateral compartment, distances were 15.3, 31.0, 30.6 and 42.3 mm to the JL.
      Strong correlation was found between femoral width and distances from the AT, ME
      and LE to the JL. CONCLUSION: In TKA, the JL is usually altered due to the
      classic resection technique, which does not respect the natural deviation of the
      JL. Estimating the natural JL by adding absolute values to bony landmarks, as
      proposed in the literature, is not recommended. According to our data, the JL can
      be best estimated by adding the calculated value: 6.40 + (width femur [mm] *
      0.49) to the AT.

PMID- 24570154
TI  - [Not Available].

PMID- 24570153
TI  - Toward the interpretation of the combined effect of size and body weight on the
      tribological performance of total knee prostheses.
AB  - PURPOSE: The research questions of the present study were: (1) Is total knee
      prosthesis wear behaviour influenced by implant size, body weight and their
      combined effect? (2) Are these findings significant and helpful from a clinical
      point of view? METHODS: Two very different sizes of the same total knee
      prosthesis (TKP), previously tested with ISO 14243 parameters, were tested on a
      knee simulator for a further two million cycles using a modified ISO 14243 load
      waveform. Roughness examination was performed on the metallic components.
      Gravimetric and micro-Raman spectroscopic analyses were carried out on the
      polyethylene inserts. RESULTS: The average volumetric mass loss was 69 +/- 3
      mm(3) and 88 +/- 4 mm(3) for smaller and bigger size, respectively. Bigger TKPs
      are little influenced by an increased load, while the wear trend of the smaller
      TKP showed a redoubled slope, and more significant morphology changes were
      observed. However, the two sizes seem to behave similarly when subjected to a
      load increase of 15 %; the slope of the volumetric mass loss trend was comparable
      for the two sets of inserts, which did not appear significantly different also at
      the molecular level. Roughness average parameters of the lateral femoral condyle
      support this evidence. CONCLUSIONS: It can be asserted that the body weight and
      implant size are relevant to the understanding of TKP wear behaviour. A post
      implantation body weight increase in a patient with smaller knee dimensions could
      results in more critical effects on prosthesis long-term performance.

PMID- 24570155
TI  - Comparative strength measurements of five different fixation systems applied on
      an in vitro model of femoral midshaft osteotomy.
AB  - Oblique midshaft fractures of long bones can be stabilized using either plates
      and screws, lag screws, wires, cerclages, or a combination of these methods.
      Fractures at the distal tip of a well-fixed femoral prosthesis are difficult to
      stabilize with plates and screws because of the underlying intramedullary stem,
      polymethylmetacrylate (PMMA) cement, and thin periprosthetic femoral cortex. In
      this study we compared in vitro the mechanical performance of five different
      osteosynthesis techniques applied on an oak femoral model obliquely oscillated to
      mimic a short oblique fracture: (a) Double stainless steel wiring; (b) two 4.5 mm
      lag screws; (c) combination of one 4.5 mm cortical screw and one stainless steel
      wire; (d) one titanium compression cerclage Gundolf (CCG) combined with one 4.5
      mm screw; and (e) double CCG. The five fixation constructs were subjected to a
      noncyclic destructive axial compression and torsional loading. The highest torque
      stiffness proved to be the double CCG and the double screw constructs, followed
      by and combination of CCG-screw and double screw constructs. The mode of failure
      in torque was a longitudinal crack close to the screw tip and loosening of the
      CCG and wire. The double screw, double CCG, and screw-CCG constructs provided the
      highest stiffness in axial compressive forces. The mode of failure in compression
      was loosening of the CCG and wire and bending of the screw. This comparative
      study showed that double CCG can theoretically replace the conventional methods
      of "minimal" osteosynthesis in the midshaft of long bones, and thus shows promise
      in the treatment of difficult short-oblique type femoral fracture at the distal
      tip of a well-fixed femoral prosthesis. The advantages of using the CCG is
      simplicity of technique, biocompatibility of titanium, no interference in modern
      imaging techniques, and avoidance of stripping of muscles and degloving of bone
      surfaces, as often happens in platting. 

PMID- 24570156
TI  - Bone density in osteoarthritic femoral heads removed at joint replacement surgery
      - quantitative assessment by histologic and fine-detail radiographic analysis.
AB  - Objective. To determine if there is a change in bone density in osteoarthritic
      femoral heads removed at joint replacement surgery and to compare bone density in
      different arthropathies. Materials and methods. All femoral heads removed at
      joint replacement surgery at St. Michael's Hospital were examined in the
      Laboratory of Bone and Joint Pathology, intact as received, following sectioning
      in the coronal and sagittal planes by fine-detail, low-energy radiology with high
      resolution, single-emulsion film. Sections were submitted for histomorphology and
      the study was undertaken to determine quantitatively, with the computer-assisted
      system, the bone density of the femoral heads. Results. Values in non-weight
      bearing areas of cases of rheumatoid arthritis, fracture, and some zones of
      osteoarthritis were below normal values. The interesting feature was that the
      cortex at the calcar of the neck tended to show a greater porosity than expected
      for cortical bone in all cases. There was difference in density, with statistical
      significance in comparing weight-bearing zones of osteoarthritis versus fracture,
      and in osteonecrosis versus fracture, in both weight-bearing and non-weight
      bearing zones. There was a strong statistically significant difference in P
      values between the weight-bearing and non-weight-bearing areas of patients with
      osteoarthritis and a relatively nonsignificant difference in patients with
      rheumatoid arthritis. There also was a statistically significant difference
      between weight-bearing and non-weight-bearing areas in the patients with
      fractures. Conclusion. The study demonstrated the static morphologic and
      morphometric variables in surgically resected femoral heads at the time of total
      hip arthroplasty. Obviously, this data is not a measure of outcome but must be
      regarded as a potential indicator of implant/host bone relationship with
      morphologic and morphometric implications. One can only speculate that assessment
      of bone density/porosity can be a predictor of long-term outcome. 

PMID- 24570157
TI  - Avascular necrosis of the head in paediatric hip fractures, an inevitable
      complication.
AB  - Hip fracture in patients with open physis is known for its low occurrence rate.
      However, despite its rare presentation, this type of fracture is known for its
      serious complications. Avascular necrosis (AVN), coxa vara, premature closure of
      the physis and secondary displacement are major complications that will determine
      prognosis. AVN with associated growth disturbances is the most serious
      complication and also an influential factor in predicting the outcome. This paper
      reports a retrospective study of 20 children who sustained a hip fracture
      according to Delbet type I-IV followed for at least 2 years. AVN was observed in
      four patients (21%), two of whom developed a complete AVN Ratliff type I within 6
      months, requiring reconstructive surgery. Non-AVN-associated coxa vara (n=5) and
      re-displacement (n=3) are complications with less serious effects on outcome. Our
      clinical results regarding AVN and its risk factors - such as age group and type
      of fracture - are comparable to the results of other documented reports. An
      overview of both avoidable and inevitable AVN risk factors, including possible
      preventative measures, is presented in this report. 

PMID- 24570158
TI  - Short-term results with the Zweymueller-SL metal-on-metal total hip arthroplasty.
AB  - In a prospective study we followed 266 consecutive patients who received 350
      Zweymueller-SL uncemented total hip replacements with metal-on-metal articulation
      for osteoarthritis. Mean follow-up was 52 (range 37-92) months. Patient age at
      the time of surgery was 55+/-9 (25-70) years. Pre-operative Harris score of 45+/
      19 was increased post-operatively to 96+/-4. Pre-operative invalidity was
      significantly improved post-operatively (P<0.001), and 97% of the patients were
      either satisfied or very satisfied with the results. There was no aseptic
      loosening of either component. Revision was made in six hips (1.8%) because of
      either septic loosening (five, 1.5%) or technical error (one, 0.3%). At revision,
      surgical microscopic evidence for metalosis (Mirra grades 1 and 2) was shown in
      all revised hips. The reasons for early loosening were unrelated to the metal-on
      metal bearing but rather were the result of either low-grade deep infection or
      inadequate surgical technique. Survival rate for Zweymueller screw socket and
      stem 7.6 years after implantation was 99.4% and 96.8% respectively. There was no
      evidence that metal-on-metal articulation gives rise to new problems or
      complications. 

PMID- 24570159
TI  - The utility of gait analysis in the rehabilitation of patients after surgical
      treatment of Achilles tendon rupture.
AB  - The purpose of our examinations was to determine whether gait analysis can
      provide evidence of functional deficits in patients with surgically treated
      ruptures of the Achilles tendon, and whether measurable parameters for
      rehabilitation result. In a retrospective study, we examined 30 patients with
      traumatic Achilles tendon rupture who had been surgically treated immediately
      posttraumatically with direct tendon suturing between May 1996 and November 1999.
      We used gait analysis and applied the Hannover Achilles tendon score with regard
      to occupational and athletic disability. The average follow-up examination
      interval was 24 (range 18-28) months. After processing results and placing
      patients in deficit-oriented therapy, a final assessment was conducted using the
      score mentioned above and a gait analysis. Prior to beginning deficit-oriented
      therapy, the 100-point score showed that, after an Achilles tendon rupture, 66.7%
      of the patients had a good to very good outcome. Gait analysis indicated
      significant deficits in functional mobility during the swing phase, manifesting
      as a diminishment of the active heel lift. At the time of the final assessment,
      the findings from gait analysis demonstrated that these deficits were no longer
      evident to any significant extent. The 100-point score from the final assessment
      yielded an increase in good and very good results to a total of 80.0%. Gait
      analysis is suited to both the detection of functional deficits following
      reconstructive surgery on the musculoskeletal system and to devising individual,
      patient-oriented rehabilitation plans. 

PMID- 24570160
TI  - Accessory coracobrachialis muscle as a cause of anterior impingement syndrome of
      the rotator cuff in an athlete.
AB  - Subcoracoid impingement is a rare but well-know cause of anterior shoulder pain
      in throwing and overhead athletics. Bulging of the walls or the contents of the
      coracohumeral space may hamper the smooth gliding of soft tissue between the
      coracoid process and glenohumeral joint, especially in forward elevation and
      internal rotation of the arm. Following is a case report of subcoracoid
      impingement caused by an accessory coracobrachialis muscle in an alpinist treated
      by resection of the muscular supernumerary slip. 

PMID- 24570161
TI  - Compartment syndrome of the shoulder girdle.
AB  - We report a case of subacute compartment syndrome involving the deltoid muscle of
      a young person. We discuss the presentation, predisposing factors, investigation
      and treatment of this otherwise rare condition. 

PMID- 24570162
TI  - Fracture-dislocation of the hip with ipsilateral femoral neck fracture.
AB  - Fracture-dislocation of the hip associated with fracture of the femoral neck and
      intrapelvic intrusion of the femoral head is a rare injury. In this case we
      performed open reduction for the femoral neck fracture, and external fixation for
      the pelvic fracture by Judet-Meyers method. As a result the patient has not
      complained of pain, although he developed arthrokleisis due to ectopic
      ossification around the femoral head, as well as femoral head necrosis. 

PMID- 24570163
TI  - Dislocation of bipolar hemiarthroplasty following breakage of the polyethylene
      ring.
AB  - Dislocation after bipolar hemiarthroplasty is rare. In classical dislocations of
      bipolar prosthesis, the prosthetic femoral head escapes from the natural
      acetabular cavity. Two cases of a bipolar hip prosthesis are presented in which
      the dislocation occurred between the cup and the metallic ball head 4 and 12
      months postoperatively. The reason for the dislocation was fracturing of the edge
      of the polyethylene ring - either due to impingement at the full flexion position
      of the hip or to dislocating forces in extreme positions of the metallic ball
      head. To avoid this complication we recommend installation of the notch of the
      polyethylene ring be at the peripheral half of the acetabular cup. 

PMID- 24570164
TI  - Traumatic dislocation of hip joint following low-velocity trauma, similarities to
      glenohumeral instability.
AB  - Acute posterior hip dislocation following low velocity trauma in a young healthy
      adult is a rare injury. Almost 30 cases previously have been described in the
      literature. They are usually associated with prior trauma to the hip joint and
      will lead to recurrent instability after relocation. This injury is similar to
      shoulder instability: lesions and anomalies present in the hip joint with
      posterior instability are identical to the ones in the shoulder with instability.
      These are Bankart-like lesion of the posterior labrum, defect in ischiofemoral
      ligament similar to inferior glenohumeral ligament laxity of the shoulder,
      relative retroversion of femoral neck angle similar to loss of retroversion of
      the humeral neck and, finally, Pipkin type 1 fracture of the femoral head
      resembling a Hill-Sachs lesion of the humeral head. Successful treatment of this
      injury depends on addressing these pathologies. We present three cases of acute
      posterior hip dislocation in young adults after low-energy trauma, which
      presented to our unit over a 4-year period, and a review of another 21 cases of
      similar injury previously described in the literature. We will demonstrate these
      lesions and discuss the investigation and treatment modalities for posterior
      instability of the hip joint. We conclude that hip dislocation caused by low
      energy trauma must be investigated and treated to avoid recurrence of dislocation
      and associated complications. 

PMID- 24570165
TI  - Stingray injury to the ankle.
AB  - We are reporting on a case of traumatic ankle penetration by the sting of a
      stingray that occurred in the West Indies. Clinical presentation, management and
      revue of the literature are also presented. 

PMID- 24570166
TI  - Sixth International Argos Symposium: Lumbar and lumbo-sacral fusions: Operative
      indications and surgical strategies.

PMID- 24570167
TI  - Adjusting for bias in C-reactive protein levels when using a vitros slide method
      in infants.
AB  - OBJECTIVE: Low total serum protein levels may cause a positive bias on C-reactive
      protein (CRP) detected by the Vitros 250 Chemistry System (Ortho-Clinical
      Diagnostics, Inc., Johnson & Johnson Co., Raritan, NJ). Low total serum protein
      levels are observed in some infants. Our objective was to define a cutoff value
      for normal levels of CRP measured on the Vitros System that is comparable to the
      cutoff value of 1.0 mg/dL measured by rate nephelometry on a Beckman Array System
      (Beckman Instruments Inc., Fullerton, CA). STUDY DESIGN: CRP was prospectively
      measured on the same serum sample on Vitros and Beckman systems. Using a result
      of >=1.0 as the "gold standard" definition of an abnormal CRP, measures of
      association were calculated. RESULTS: CRP was measured in 981 blood samples that
      were collected from 361 infants. A cutoff CRP level using the Vitros system at
      1.5 mg/dL had the highest sensitivity and negative predictive value comparable to
      1.0 mg/dL measured by nephelometry. By regression analysis, each increase by 1
      mg/dL by nephelometry caused an increase by 1.5 mg/dL on the Vitros system (R(2)
      = 0.94; p < 0.001; slope = 0.66; 95% confidence intervals, 0.65, 0.67).
      CONCLUSION: In infants, when measuring CRP levels by Vitros CRP slide system, a
      normal reference level of 1.5 mg/dL instead of 1 mg/dL should be used.

PMID- 24570168
TI  - The history of fetal therapy.
AB  - The Fetal Treatment Center founded by Michael Harrison is credited as the
      birthplace of fetal surgery. His trainees in pediatric surgery subsequently
      founded fetal centers throughout the United States. In Europe, the advent of
      minimally invasive fetal surgical techniques led to the establishment of
      treatment centers led predominantly by perinatologists. More recently,
      perinatologists in North America have begun to play a greater role in the field
      of fetal intervention.Intrauterine transfusion for the treatment of hemolytic
      disease of the fetus/newborn was the first successful fetal intervention.
      Although not subjected to the rigors of clinical trials, this treatment has
      withstood the test of time. Interventions for other fetal disease states such as
      twin-twin transfusion and repair of fetal myelomeningocele were investigated in
      animal models followed by randomized clinical trials before widespread adoption.
      Tracheal occlusion for diaphragmatic hernia is still currently being investigated
      as the next promising step in fetal intervention. 

PMID- 24570169
TI  - Genomic analysis of NAC transcription factors in banana (Musa acuminata) and
      definition of NAC orthologous groups for monocots and dicots.
AB  - Identifying the molecular mechanisms underlying tolerance to abiotic stresses is
      important in crop breeding. A comprehensive understanding of the gene families
      associated with drought tolerance is therefore highly relevant. NAC transcription
      factors form a large plant-specific gene family involved in the regulation of
      tissue development and responses to biotic and abiotic stresses. The main goal of
      this study was to set up a framework of orthologous groups determined by an
      expert sequence comparison of NAC genes from both monocots and dicots. In order
      to clarify the orthologous relationships among NAC genes of different species, we
      performed an in-depth comparative study of four divergent taxa, in dicots and
      monocots, whose genomes have already been completely sequenced: Arabidopsis
      thaliana, Vitis vinifera, Musa acuminata and Oryza sativa. Due to independent
      evolution, NAC copy number is highly variable in these plant genomes. Based on an
      expert NAC sequence comparison, we propose forty orthologous groups of NAC
      sequences that were probably derived from an ancestor gene present in the most
      recent common ancestor of dicots and monocots. These orthologous groups provide a
      curated resource for large-scale protein sequence annotation of NAC transcription
      factors. The established orthology relationships also provide a useful reference
      for NAC function studies in newly sequenced genomes such as M. acuminata and
      other plant species. 

PMID- 24570170
TI  - Association between internalizing disorders and day-to-day activities of low
      energetic expenditure.
AB  - The objective of this study is to compare energetic expenditure in day-to-day
      activities among subjects with internalizing disorders (depression and anxiety),
      externalizing disorders (attention deficit/hyperactivity disorder and
      oppositional defiant disorder) and healthy children and adolescents without any
      psychiatric diagnosis. One hundred and five (n = 105) students from a community
      sample were evaluated throughout a structured psychiatric interview and
      categorized into three groups: internalizing (n = 54), externalizing (n = 12) and
      typically developing controls (TDC, n = 39). Energetic expenditure was evaluated
      using 3-day physical activity record. Subjects with internalizing disorders
      performed activities with lower energetic expenditure as compared to those with
      externalizing disorders and TDC. Participants with externalizing disorders had
      more energetic expenditure variability. Our study suggests that internalizing
      disorders are associated with activities of low energetic expenditure in day-to
      day activities, extending previous findings with physical exercise. These
      findings may further contribute to the understanding of the associated morbidity
      previously described in patients with internalizing disorders.

PMID- 24570171
TI  - Ruminative and catastrophizing cognitive styles mediate the association between
      daily hassles and high anxiety in Hong Kong adolescents.
AB  - This study assessed rumination, catastrophizing and daily hassles as predictors
      of anxiety when controlling for depressive symptoms in a community sample of
      adolescents reporting high anxiety. Adolescents aged 12-18 (N = 2,802, mean age
      of 14.9) completed the Screen For Child Anxiety-Related Emotional Disorders. With
      a total score of 30 as the cutoff, a group of high anxiety adolescents was
      identified (a prevalence rate of 28.02%). Path analyses results showed that
      amongst the high anxiety boys, catastrophizing but not rumination was a positive
      predictor of anxiety and it mediated the effects of daily hassles on anxiety. In
      the high anxiety girls, both rumination and catastrophizing predicted anxiety but
      only catastrophizing was the mediator between daily hassles and anxiety. It is
      suggested that such gender differences in cognitive responses styles should be
      considered in cognitive-behavioral therapeutic approaches designed to help
      adolescents showing high anxiety.

PMID- 24570172
TI  - The expression of aquaporins 1 and 5 in rat lung after thoracic irradiation.
AB  - Radiation-induced lung toxicity (RILT), leading to radiation pneumonia or
      fibrosis, is a primary problem of radiation therapy. The pathogenesis of RILT
      remains unclear. In this study, we used a rat model of RILT to examine the
      expression of aquaporins (AQPs) after radiation injury. Sprague Dawley rats were
      given a single dose of 17 Gy (dose rate of 3.0 Gy/min) of X-irradiation to the
      thorax. Rats that survived acute pneumonitis (at 1-4 weeks) were evaluated weekly
      for the expression of AQP1 and AQP5 in the lung by immunohistochemical and
      reverse transcription polymerase chain reaction (RT-PCR) analyses.
      Immunohistochemical analysis showed that AQP1 protein was expressed in the
      capillary endothelium, and its level was significantly decreased after
      irradiation. AQP5 protein was expressed in the alveolar epithelium, and its level
      was increased between Days 7 and 14 after irradiation but decreased at Day 28,
      compared with the sham group. The RT-PCR results were consistent with the
      immunohistochemical analysis results. In summary, this study provides the first
      report of AQP1 and AQP5 expression in a model of radiation-induced pulmonary
      inflammation and edema. Decreased levels of AQP1 and AQP5 after irradiation
      suggest that these proteins play a role in the pathogenesis of RILT.

PMID- 24570173
TI  - Profiling of low molecular weight proteins in plasma from locally irradiated
      individuals.
AB  - In studies reported in the 1960s and since, blood plasma from radiation-exposed
      individuals has been shown to induce chromosome damage when transferred into
      lymphocyte cultures of non-irradiated persons. This effect has been described to
      occur via clastogenic factors, whose nature is still mostly unknown. We have
      previously examined clastogenic factors from irradiated individuals by looking at
      plasma-induced DNA damage in reporter cells. Plasma was tested from ca. 30
      locally exposed clinical patients receiving fractionated radiation treatment, as
      well as from three radiological accident victims exposed in 1994, albeit sampled
      14 years post-accident. In the current work, proteome changes in the plasma from
      all subjects were examined with 2D gel electrophoresis-based proteomics
      techniques, in order to evaluate the level of protein expression with respect to
      the findings of a clastogenic factor effect. No differences were observed in
      protein expression due to local radiation exposure (pre- vs post-exposure). In
      contrast, plasma from the radiation accident victims showed alterations in the
      expression of 18 protein spots (in comparison with plasma from the control
      group). Among these, proteins such as haptoglobin, serotransferrin/transferrin,
      fibrinogen and ubiquitin-60S ribosomal protein L40 were observed, none of them
      likely to be clastogenic factors. In conclusion, the proteomics techniques
      applied were unable to identify changes in the proteome of the locally irradiated
      patients, whereas such differences were observed for the accident victims.
      However, association with the clastogenic effect or any specific clastogenic
      factor remains unresolved and thus further studies with more sensitive techniques
      are warranted.

PMID- 24570174
TI  - Preliminary results of a novel quorum sensing inhibitor against pneumococcal
      infection and biofilm formation with special interest to otitis media and
      cochlear implantation.
AB  - The purpose of the study is to assess the effect of a novel quorum sensing
      inhibitor (QSI), coded as 'yd 47', against otitis media and biofilm formation on
      Cochlear implants (CIs). Small pieces cut from cochlear implant were implanted
      under the skin in the retroauricular area on both sides of four guinea pigs. The
      implant pieces in the study and control sides were implanted in Streptococcus
      pneumoniae strain solution and saline, respectively. The right and left middle
      ears were also instilled with a solution containing pneumococci and saline,
      respectively. The animals were only given an intraperitoneal 'yd 47' twice daily
      for three months to be assessed later with electron microscopy. Clinical
      examination with palpation, inspection and otoscopy did not reveal any sign of
      implant infection or otitis media. In the study and control implant materials,
      soft tissues around the implant and tympanic membranes, there was no biofilm
      formation by pneumococci. Contamination by various cells and some rod-shaped
      bacteria (not diplococcic) were seen in some of the materials. In conclusion, the
      novel QSI seems promising in the prevention of otitis media and biofilm formation
      on CIs by pneumococci.

PMID- 24570175
TI  - Chemical labyrinthectomy for the worse ear of adult Nigerians with bilateral
      Meniere's disease: preliminary report of treatment outcomes.
AB  - The objective of this study was to assess the effectiveness of variable
      titration, low-dose intratympanic gentamycin (ITG) into the worse affected ear of
      patients with bilateral Meniere's disease (MD). It is a prospective analytic case
      series conducted in a tertiary care referral hospital in a developing economy and
      a tertiary care otologic private ENT clinic. Patients with MD who failed or are
      intolerant to medical treatment were recruited based on the criteria of definite
      MD and bilateral ear involvement. 0.75 cc of low-dose (40 mg/ml) buffered
      gentamycin was injected into the worse affected ear and patients followed up
      every 2 months, and the regime repeated only if subjective vertigo persists. The
      patient's age, sex, duration of MD symptom, ear first affected, ear selected for
      ITG, pure tone threshold at each visit, duration of caloric response (in seconds)
      for the injected ear, status of tinnitus in both ipsilateral (injected) and
      contralateral ears, total number of injections before last follow-up, and time
      since last follow-up are entered into the study protocol and analyzed. Nine
      patients with a mean age of 45 years and mean duration of symptoms of 59 months
      were treated. The mean total number of injections was 2.8 with a mean follow-up
      period of 34 months. Three cases showed drop in pure tone average threshold (2.5
      7.5 dB) while an increase in threshold was noted in six cases (2.5-5 dB). All
      cases demonstrated decrease in duration of response to iced water caloric
      stimulation in ipsilateral ear, and 4/9 of contralateral ear. The variable
      titration method using low-dose intratympanic gentamycin directed at worse ear of
      adult Nigerians with bilateral Meniere's disease appears to be highly effective.
      More studies are needed.

PMID- 24570176
TI  - Mosaic RNA phage VLPs carrying domain III of the West Nile virus E protein.
AB  - The virus-neutralising domain III (DIII) of the West Nile virus glycoprotein E
      was exposed on the surface of RNA phage AP205 virus-like particles (VLPs) in
      mosaic form. For this purpose, a 111 amino acid sequence of DIII was added via
      amber or opal termination codons to the C-terminus of the AP205 coat protein, and
      mosaic AP205-DIII VLPs were generated by cultivation in amber- or opal
      suppressing Escherichia coli strains. After extensive purification to 95 %
      homogeneity, mosaic AP205-DIII VLPs retained up to 11-16 % monomers carrying DIII
      domains. The DIII domains appeared on the VLP surface because they were fully
      accessible to anti-DIII antibodies. Immunisation of BALB/c mice with AP205-DIII
      VLPs resulted in the induction of specific anti-DIII antibodies, of which the
      level was comparable to that of the anti-AP205 antibodies generated against the
      VLP carrier. The AP205-DIII-induced anti-DIII response was represented by a
      significant fraction of IgG2 isotype antibodies, in contrast to parallel
      immunisation with the DIII oligopeptide, which failed to induce IgG2 isotype
      antibodies. Formulation of AP-205-DIII VLPs in alum adjuvant stimulated the level
      of the anti-DIII response, but did not alter the fraction of IgG2 isotype
      antibodies. Mosaic AP205-DIII VLPs could be regarded as a promising prototype of
      a putative West Nile vaccine.

PMID- 24570177
TI  - Transplantation of human adipose-derived stem cells enhances remyelination in
      lysolecithin-induced focal demyelination of rat spinal cord.
AB  - Adipose-derived stem cells (ADSCs) are a desirable stem cell source in
      neurodegenerative diseases treatment due to their ability to differentiate into
      different cell lineages. In this study, we transplanted human ADSCs (hADSCs) into
      a lysophosphatidylcholine (lysolecithin) model of multiple sclerosis (MS) and
      determined the efficiency of these cells in remyelination process. Forty adult
      rats were randomly divided into control, lysolecithin, vehicle, and
      transplantation groups, and focal demyelination was induced by lysolecithin
      injection into spinal cord. To assess motor performance, all rats were examined
      weekly with a standard EAE scoring scale. Four weeks after cell transplantation,
      to assess the extent of demyelination and remyelination, Luxol Fast Blue staining
      was used. In addition, immunohistochemistry technique was used for assessment of
      the presence of oligodendrocyte phenotype cells in damaged spinal cord. Our
      results indicated that hADSCs had ability to differentiate into oligodendrocyte
      phenotype cells and improved remyelination process. Moreover, the evaluation of
      rat motor functions showed that animals which were treated with hADSC compared to
      other groups had significant improvement (P < 0.001). Our finding showed that
      hADSCs transplantation for cell-based therapies may play a proper cell source in
      the treatment of neurodegenerative diseases such as MS.

PMID- 24570178
TI  - Apolipoprotein E mutations: a comparison between lipoprotein glomerulopathy and
      type III hyperlipoproteinemia.
AB  - Apolipoprotein E (ApoE) serves as a ligand for the low-density lipoprotein (LDL)
      receptor and cell surface receptors of the LDL receptor gene family. More than 10
      different causative apoE mutations associated with lipoprotein glomerulopathy
      (LPG) have been reported. ApoE polymorphisms including three common phenotypes
      (E2, E3, E4), and a variety of rare mutations can affect blood cholesterol and
      triglyceride levels. The N-terminal domain of apoE is folded into a four-helix
      bundle of amphipathic alpha-helices, and contains the receptor-binding domain in
      which most apoE mutations that cause LPG or dominant mode of type III
      hyperlipoproteinemia (HL) are located. No single apoE mutation has been reported
      that causes both LPG and the dominant mode of type III HL. 

PMID- 24570179
TI  - Immediate implant breast reconstruction with acellular dermal matrix for
      treatment of a large recurrent malignant phyllodes tumor.
AB  - Phyllodes tumors (PT) are rare fibroepithelial breast tumors representing less
      than 1 % of all breast malignancies. These tumors are unpredictable and fast
      growing with a high local recurrence rate, making this disease challenging to
      treat. Previous literature focused on surgical resection, and breast
      reconstruction following a mastectomy in patients with PT is rarely addressed. We
      report a case of a recurrent malignant PT treated with a nipple-sparing
      mastectomy followed by immediate single-stage silicone implant breast
      reconstruction. While PT is a rare breast malignancy that presents challenges
      with both surgical resection and reconstruction, we demonstrate that nipple
      sparing mastectomy with immediate implant breast reconstruction with AlloMax is
      curative and can offer an appealing cosmetic option. 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- 24570180
TI  - Tattoo ink-related cutaneous pseudolymphoma: a rare but significant complication.
      Case report and review of the literature.
AB  - BACKGROUND: The demand for decorative tattoos is steadily growing worldwide, and
      in the US it is estimated that up to 24% of adults has one or more tattoos.
      Subsequently, the number of tattoo-related complications is increasing. Among
      these, lymphoproliferative disorders play a minor but important role. The aim of
      this article is to arouse the awareness of plastic surgeons and dermatologists
      about this rare but serious complication and to stimulate stricter clinical
      control of their tattooed patients. METHODS: We report a new case of tattoo
      related cutaneous pseudolymphoma (CPL) and perform a review of the last 30 years
      of literature on the topic in PubMed. RESULTS: Apart from this new case, only 18
      cases of CPL have been reported in PubMed so far. In contrast to the classic
      knowledge, the T cell was the predominant phenotype in 68% of cases. Red is
      confirmed to be the most involved ink. Topical and intralesional steroids, laser
      therapy, and surgery were used for treatment of CPL. CONCLUSIONS: Even if CPL is
      a very rare and benign complication, we should not forget that in rare cases
      pseudolymphoma may evolve into a true lymphoma. Diagnosis is still difficult and
      is based on anamnestic, clinical, and histopathological data. From the review of
      the literature, the T cell predominance suggests a reclassification of tattoo
      induced CPL and there is not a gold standard treatment yet. Finally, once a
      pseudolymphoma is diagnosed, there must be a long follow-up because of the
      possibility to transform into a malignancy. 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- 24570182
TI  - The efficacy of bevacizumab plus paclitaxel as first-line treatment for HER2
      negative metastatic breast cancer: a meta-analysis of randomized controlled
      trials.
AB  - Although both bevacizumab and paclitaxel significantly improve the efficacy of
      chemotherapy for human epidermal growth factor receptor 2 (HER2)-negative
      patients with metastatic breast cancer (MBC), little have changed with overall
      survival rates when they have been used alone or combined with other
      chemotherapy. Thus, a meta-analysis was conducted to evaluate the efficacy of
      bevacizumab combined with paclitaxel in HER2-negative MBC patients. Pubmed and
      Embase were systematically reviewed for studies published up to September 2013 in
      which bevacizumab plus paclitaxel were compared with other chemotherapy. Primary
      outcomes comprised overall survival (OS), progression-free survival (PFS), and
      objective response rate (ORR). Eight phase II/III clinical trials met the
      inclusion criteria, with a total of 3,758 patients. The pooled results showed
      that combination of bevacizumab and paclitaxel significantly improved the PFS (HR
      = 0.63, 95% CI, 0.55-0.73, P = 0.011), ORR (RR = 1.28, 95% CI, 0.96-1.70, P =
      0.0), but had no effect on OS (HR = 0.91, 95% CI, 0.81-1.01, P = 0.855). The meta
      analysis confirms the benefits of bevacizumab-paclitaxel combination therapy in
      HER2 negative metastatic breast cancer, with an improvement in both progression
      free survival and objective response rate. However, no significant OS benefit was
      observed.

PMID- 24570183
TI  - Bufalin inhibited the growth of human osteosarcoma MG-63 cells via down
      regulation of Bcl-2/Bax and triggering of the mitochondrial pathway.
AB  - Cinobufacini (Huachansu), a Chinese medicine prepared from the skin of Bufo bufo
      gargarizans Cantor (Bufonidae), has potent anti-tumor activity in vitro and in
      vivo. However, the molecular mechanism of cell apoptosis induced by Bufalin
      remains elusive. Here, we investigated the apoptosis in Bufalin-treated human
      osteosarcoma MG-63 cells. The results showed that Bufalin could inhibit cell
      proliferation and induce apoptosis in a dose- and time-dependent manner. Further
      investigation revealed that a disruption of mitochondrial transmembrane potential
      (MMP) and an up-regulation of reactive oxygen species (ROS) in Bufalin-treated
      cells. By western blot analysis, we found that the up-regulation of Apaf-1,
      cleaved PARP, cleaved caspase-3, cleaved caspase-9, and Bax/Bcl-2, varies with
      different concentration of Bufalin. These protein interactions may play a pivotal
      role in the regulation of apoptosis. Taken together, these results overall
      indicate that Bufalin could be used as an effective anti-tumor agent in therapy
      of osteosarcoma targets the mitochondrial-dependent signaling pathway. 

PMID- 24570184
TI  - Increased expression of IL17A in human gastric cancer and its potential roles in
      gastric carcinogenesis.
AB  - Inflammatory cytokines modulate immune responses in the tumor microenvironment
      during progression. The role of interleukin (IL) 17A in cancer is currently under
      debate. We aim to investigate the expression of IL17A in situ tumors as well as
      in nontumor gastric mucosa tissues and further explore the functional
      significance of IL17A on gastric cancer cells in vitro. We found that compared
      with nontumor regions, the expression of IL17A were increased significantly in
      tumors of gastric cancer patients (P=0.007). The immunoreactivity for IL17A was
      found only in cytoplasm of inflammatory cells as well as vascular endothelial
      cells but not in tumor cells. Consistently, IL17A transcription was silenced in a
      variety of gastric cancer cell lines. In vitro, recombinant human IL17A protein
      promotes cell proliferation and monolayer wound healing of both AGS and
      SGC7901cells, in a dose-dependent manner. Besides, IL17A inhibits H2O2-induced
      cell apoptosis. Expression of IL6 and MMP13 mRNA was increased significantly
      after IL17A stimulation. These data suggest that accumulation of intratumoral
      IL17A-producing cells may promote gastric cancer progression directly or by
      inducing key signal transduction pathways implicated in gastric carcinogenesis.

PMID- 24570185
TI  - Cyclin D1 G870A polymorphism and the risk of hepatocellular carcinoma in a
      Chinese population.
AB  - Cyclin D1, encoded by the gene CCND1, is a regulatory protein in the cell cycle
      transition from G1 phase to S phase. A common polymorphism (G870A) in the exon 4
      of CCND1 gene affects splicing of the CCND1 transcript and may cause
      uncontrollable cellular growth. Therefore, the CCND1 G870A polymorphism may
      influence an individual's susceptibility to the development of certain tumors.
      The present study was performed to test the association between G870A
      polymorphism in the CCND1 gene and hepatocellular carcinoma (HCC) risk in a
      Chinese population. We extracted the peripheral blood samples from 220 patients
      with HCC and 220 age- and gender-matched healthy controls. The polymerase chain
      reaction-restriction fragment length polymorphism (PCR-RFLP) analysis and direct
      DNA sequencing were performed to detect the polymorphism. The CCND1 genotype
      distribution among HCC patients was not significantly different from that among
      healthy controls (P=0.08). Compared with the wild-type GG genotype, neither the
      variant AA genotype nor the variant genotypes containing the A allele were
      associated with risk of HCC. However, stratification analysis by HBV carrier
      status revealed that the variant genotypes containing the A allele were
      associated with a significantly increased risk of HCC among HBsAg-positive
      individuals (adjusted OR=3.87; 95 % CI=1.12, 13.30). These results suggest that
      the CCND1 G870A polymorphism may increase the risk of HBV-related HCC in the
      Chinese population.

PMID- 24570187
TI  - The use of vancomycin powder reduces surgical reoperation in posterior
      instrumented and noninstrumented spinal surgery.
AB  - BACKGROUND: Surgical site infections can complicate posterior spine surgery.
      Multiple hospital admissions may be required to adequately treat a surgical site
      infection, which is associated with increased costs and lower patient
      satisfaction. The objective of this study was to evaluate the efficacy of
      prophylactic intra-wound vancomycin powder in reducing the incidence of repeat
      surgery for infections after posterior instrumented and noninstrumented spine
      surgery. METHODS: A series of consecutive patients who underwent instrumented or
      noninstrumented posterior spine surgery for any indication by two surgeons from
      July 2010 to July 2012 were reviewed. The preoperative antibiotic regimens of
      both surgeons were identical, except that one surgeon applied 1 g vancomycin
      powder directly to the surgical bed before wound closure, while the other did
      not. Patient demographics, operative details, and rates of reoperation for wound
      infection in the control and the treatment groups were compared. RESULTS: Both
      the control group and treatment group consisted of 150 patients; mean ages were
      58.33 and 54.14 years, respectively. Both groups had low rates of deep infection
      requiring surgical intervention. The treatment group had a significantly lower
      rate of infection requiring reoperation or surgical debridement (0 %; 95 % CI: 0
      %-2.4 %) compared with the control group (4 %; 95 % CI: 1.5 %-8.5 %) (P =
      0.0297). The six infections identified in the control group resulted in 12 repeat
      operative debridement procedures. Gram-positive organisms were identified in 66.7
      % of infections. No complications were related to the application of vancomycin
      powder. CONCLUSIONS: The results of this study demonstrate that adjunctive
      vancomycin powder applied directly to the surgical bed before closure seems
      effective in preventing deep infections that require operative debridement
      following posterior spine surgery.

PMID- 24570188
TI  - Prothrombin complex concentrate facilitates emergency spinal surgery in
      anticoagulated patients.
AB  - BACKGROUND: Oral anticoagulants are commonly used in the ageing population and
      therefore, spine surgeons are increasingly confronted with anticoagulated
      patients requiring surgical therapy. 'Bridging therapies' with heparins are
      established in elective settings, but the time frame for haemostasis restoration
      may be too long for patients presenting with acute spinal pathology and impending
      disability. The goal of this study was to analyse the feasibility of prothrombin
      complex concentrate (PCC) administration to facilitate emergency spinal surgery
      in anticoagulated patients. METHOD: A retrospective analysis of the institutional
      database of neurosurgical patients receiving PCC from February 2007 to December
      2013 (n = 485) identified 18 patients who received PCC prior to emergency spinal
      surgery. Clinical characteristics, as well as modalities of PCC administration
      and parameters of haemostasis were analysed. Furthermore, haemorrhagic
      complications and thromboembolic events in the further course were evaluated.
      RESULTS: Spinal pathologies requiring urgent neurosurgical decompression were
      spinal haematoma (n = 9), spinal metastasis (n = 5), vertebral body fracture (n =
      2), and disc herniation (n = 2). The mean international normalized ratio (INR) on
      admission was 2.27 +/- 1.20 and after administration of PCC (mean: 1,944 +/- 953
      I.U.), INR significantly decreased to 1.12 +/- 0.10 (p < 0.001). Emergency
      surgery was initiated within 4.4 h after PCC administration (range: 0-16.6 h).
      Postoperatively, symptoms improved in 12 patients (66.7 %). There were two deaths
      (11 %), one caused by acute myocardial infarction on the fourth postoperative
      day. Bleeding complications occurred in two patients (epidural haemorrhage n = 1,
      rectal tumour haemorrhage n = 1). CONCLUSIONS: The administration of PCC
      facilitates emergency spinal surgery in anticoagulated patients who present with
      acute spinal pathology requiring urgent neurosurgical decompression. The risk of
      PCC-associated thromboembolic events seems to be low and justifies the use of PCC
      in order to avoid permanent disablement resulting from delayed surgery or non
      operation.

PMID- 24570189
TI  - [Do antibodies provide advantages for the therapy of Alzheimer's disease?
      Solanezumab: the jury is still out].

PMID- 24570186
TI  - Effects of aerobic exercise on cancer-related fatigue in breast cancer patients
      receiving chemotherapy: a meta-analysis.
AB  - Increasing scientific evidences suggest that aerobic exercise may improve cancer
      related fatigue in breast cancer patients, but many existing studies have yielded
      inconclusive results. This meta-analysis aimed to derive a more precise
      estimation of the effects of aerobic exercise on cancer-related fatigue in breast
      cancer patients receiving chemotherapy. The PubMed, CISCOM, CINAHL, Web of
      Science, Google Scholar, EBSCO, Cochrane Library, and CBM databases were searched
      from inception through July 1, 2013 without language restrictions. Crude
      standardized mean difference (SMD) with 95 % confidence interval (CI) was
      calculated. Twelve comparative studies were assessed with a total of 1,014 breast
      cancer patients receiving chemotherapy, including 522 patients in the aerobic
      exercise group (intervention group) and 492 patients in the usual care group
      (control group). The meta-analysis results revealed that the Revised Piper
      Fatigue Scale (RPFS) scores of breast cancer patients in the intervention group
      were significantly lower than those in the control group (SMD=-0.82, 95% CI=-1.04
      ~ -0.60, P<0.001). However, there was no significant difference in the Functional
      Assessment of Chronic Illness Treatment-Fatigue scale (FACIT-F) scores between
      the intervention and control groups (SMD=0.09, 95% CI=-0.07 ~ 0.25, P=0.224).
      Subgroup analysis by ethnicity indicated that there were significant differences
      in RPFS and FACIT-F scores between the intervention and control groups among
      Asian populations (RPFS: SMD=-1.08, 95% CI=-1.35 ~ -0.82, P<0.001; FACIT-F:
      SMD=1.20, 95 % CI=0.70 ~1.71, P<0.001), but not among Caucasian populations (all
      P>0.05). The current meta-analysis indicates that aerobic exercise may improve
      cancer-related fatigue in breast cancer patients receiving chemotherapy,
      especially among Asian populations.

PMID- 24570190
TI  - [Endocrinology: from bench to bedside].

PMID- 24570191
TI  - [Epidemiological study on the dimension of vitamin D deficiency in North
      Germany].
AB  - BACKGROUND AND PURPOSE: In North Germany, the recommended exposure to sunlight of
      30 minutes per day to produce sufficient vitamin D is hardly achieved, in
      particular due to weather conditions. Moreover, lifestyle and working habits also
      contribute to this problem. The aim of our study was therefore to investigate the
      prevalence of the vitamin D deficiency in North Germany. METHODS: For this
      purpose, 25-hydroxy vitamin D levels of over 98,000 people from North Germany
      during the time period 2008-2011 were retrospectively analysed based on age,
      gender and season. 25-vitamin D status was divided into sufficient (> 75 nmol/l)
      and insufficient (50 to 75 nmol/l) supply as well as vitamin D deficiency (< 50
      to 25 nmol/l) and severe vitamin D deficiency (< 25 nmol/l). RESULTS: An
      undersupply of vitamin D was evident in all age groups analysed both in women and
      men in North Germany. Overall, vitamin D deficiency was particularly present
      during the months with less sunlight: more than 30 % of the people analysed
      showed a severe vitamin D deficiency in the months January to April. The study
      also showed that 25-vitamin D tests were almost evenly distributed over the
      individual months of the whole year and that this analysis was requested more
      frequently in elderly than in younger people. However, a severe vitamin D
      deficiency could also be detected in 25 % of the people analysed in the
      adolescent and young adult age group. CONCLUSION: Based on these results, it can
      be recommended to test 25-vitamin D levels once a year during the months January
      to April to detect a severe deficiency and to early initiate preventive
      supplementation.

PMID- 24570193
TI  - [19-year-old woman with nodular painless skin alterations].

PMID- 24570192
TI  - [Fine-needle aspiration cytology of thyroid nodules: molecular diagnostics in a
      routine diagnostic setting].
AB  - BACKGROUND AND OBJECTIVE: Results for the detection of point mutations and
      rearrangements have thus far been obtained by fresh material of fine needle
      aspiration cytology (FNAC). After a first retrospective study we report on the
      diagnostic detection in routinely obtained, consecutive air-dried FNAC smears.
      METHODS: RNA and DNA was extracted from 154 consecutive routine air-dried FNAC
      smears: 80 with microfollicular proliferation (MFP), 45 with follicular neoplasia
      (FN), 26 with the cytological diagnosis of papillary carcinomas (PTC) and 3 which
      were suspicious for malignancy. PAX8/PPARG and RET/PTC3 rearrangements were
      detected by qPCR, while BRAF and RAS point mutations were detected by
      pyrosequencing. RESULTS: Only 0.7 % and 5.3 % of the routine air-dried FNAC
      samples did not allow analysis of a point mutation or rearrangements,
      respectively. NRAS mutations could be detected in 7 MFP smears, and in one of FN
      and PTC samples, respectively. HRAS mutations were detected in one MPF and one FN
      sample. A KRAS mutation was only detected in one FN sample, whereas BRAF
      mutations were detected in 20 samples with PTC (but in no other sample).
      PAX8/PPARG was detected in 2 MFP samples, while RET/PTC was detected in only one
      MFP sample. In total, 13.8 % MFP-FNAC, 6.7 % FN-FNAC, and 80.8 % PTC-FNAC samples
      harbored a mutation. CONCLUSION: These results demonstrate that rearrangements
      and point mutations can be detected in routinely obtained air-dried FNAC samples.

PMID- 24570194
TI  - [Cardiac myopathy due to overt hypothyroidism].
AB  - HISTORY AND ADMISSION FINDINGS: A 51-year-old man presented with progressive
      tiredness, proximal muscle weakness, hair loss and weight gain for months. The
      patient showed mild pretibial myxedema and dry skin. Laboratory findings revealed
      strongly elevated cardiac enzymes as well as marked hypothyroidism.
      INVESTIGATIONS: The electrocardiogram, echocardiography, abdominal sonography and
      chest X-ray were unremarkable. Thyroid ultrasound demonstrated features of
      Hashimoto thyroiditis. TREATMENT AND COURSE: The findings supported the diagnosis
      of an overt hypothyroidism with myxedema and rhabdomyolysis. After starting
      levothyroxine and volume substitution laboratory parameters and clinical
      condition slowly normalized. CONCLUSION: Severe overt hypothyroidism may rarely
      present primarily as myopathy with myositis and cardiac involvement.

PMID- 24570195
TI  - [Pheochromocytoma: update on diagnosis and therapy].
AB  - Pheochromocytomas (P) are rare catecholamine producing neuroendocrine tumors
      originating from the chromaffin cells of the adrenal medulla or in 15 % of cases
      from extra adrenal chromaffin tissue and termed paragangliomas (PGL). Because of
      secretion of the catecholamines - adrenaline, noradrenaline and dopamine - the
      tumors are dangerous with a risk of life threating hypertensive crises.
      Measurements of plasma metanephrine, normetanephrine and methoxytyramine by
      liquid chromatography with tandem mass spectrometry provides the most accurate
      and precise method for biochemical diagnosis. Approximately 30-40 % of the tumors
      have a hereditary background due to mutations of 11 known susceptibility genes,
      with identification facilitated by targeted genetic testing according to clinical
      presentation. Apart from syndrome-dependent clinical stigmata, other hints to an
      underlying mutation can be provided by biochemical profiles of the catecholamine
      metabolites, tumor location, patient age and presence of metastatic disease.
      Surgery with minimal invasive procedures is the recommended therapeutic way after
      pretreatment with an alpha receptor blocking medication.

PMID- 24570196
TI  - [Prevention of diabetes mellitus--yes].

PMID- 24570197
TI  - [Prevention of diabetes mellitus--no].

PMID- 24570198
TI  - [Thyroid hormone action beyond classical concepts. The priority programme
      "Thyroid Trans Act" (SPP 1629) of the German Research Foundation].
AB  - Thyroid hormones are of crucial importance for the function of nearly all organ
      systems. In case of dysfunction of thyroid hormone production and function many
      organ systems may be affected. The estimation of normal thyroid function is based
      on determination of TSH and the thyroid hormones T3 and T4. However,
      international conventions about the normal TSH range are still lacking which
      bears consequences for patient's treatment. Hence not unexpected, many patients
      complain although their thyroid hormone status is in the normal range by clinical
      estimation. Here, more precise parameters are needed for a better definition of
      the healthy thyroid status of an individual. Recently, new key players in the
      system of thyroid hormone action were detected, like specific transporters for
      uptake of thyroid hormones and thyroid hormone derivatives. DFG, the German
      Research Foundation supports the priority program Thyroid Trans Act to find
      answers to the main question: what defines the healthy thyroid status of an
      individual. The overall aim of this interdisciplinary research consortium is to
      specify physiological and pathophysiological functions of thyroid hormone
      transporters and thyroid hormone derivative as new players in thyroid regulation
      in order to better evaluate, treat, and prevent thyroid-related disease. 

PMID- 24570199
TI  - [Drug treatment of osteoporosis].

PMID- 24570200
TI  - [Medical care: equal opportunities and minimum standards between rationalization
      and rationing].

PMID- 24570201
TI  - Optimal surgical management for esophagogastric junction carcinoma.
AB  - OBJECTIVES: Esophagogastric junction carcinoma incidence is increasing worldwide.
      However, surgical strategies for this cancer remain controversial. This study
      aimed to clarify the optimal surgical strategy for esophagogastric junction
      carcinoma. METHODS: We retrospectively reviewed a database of 68 consecutive
      patients with esophagogastric junction carcinoma [Japanese classification of
      gastric carcinoma (Nishi's definition): adenocarcinoma, N=53; squamous cell
      carcinoma, N=15] who underwent curative surgical resection at Keio University
      Hospital between January 2000 and September 2008. RESULTS: In both adenocarcinoma
      and squamous cell carcinoma, most lymph node metastases were located in the
      lesser curvature area. Mediastinal lymph node metastasis was observed in 4
      patients (7.5%) with adenocarcinoma and 7 patients (46.7%) with squamous cell
      carcinoma. No patient presented with lymph node metastases in the pyloric region.
      The therapeutic value of extended lymph node dissection was 0, except for lymph
      node station numbers 1, 2, 3, 4sa, 7, and 110. Extended lymph node dissection in
      the lesser curvature area showed a high therapeutic value. The para-aortic lymph
      node was the most frequent nodal recurrence site. All patients with tumor centers
      located below the esophagogastric junction (N=37) did not develop mediastinal
      lymph node metastasis or recurrence. CONCLUSIONS: Proximal gastrectomy through a
      transhiatal approach may be the optimal surgical strategy for esophagogastric
      carcinoma. Mediastinal lymph node dissection through a thoracic approach seems
      unnecessary, particularly when the tumor center is located below the
      esophagogastric junction. To confirm the necessity of para-aortic nodal
      dissection, further studies are required.

PMID- 24570202
TI  - Correlates of depressive symptoms in urban middle-aged and elderly Lithuanians.
AB  - PURPOSE: The study aimed to examine the prevalence of depressive symptoms and
      their correlates in urban middle-aged and elderly Lithuanian adults. METHODS:
      Data from the survey was collected within the framework of the international
      project HAPIEE (Health, Alcohol and Psychosocial Factors in Eastern Europe). A
      random sample of 7,115 individuals aged 45-72 years was screened in 2006-2008.
      RESULTS: Depressive symptoms were differently associated with independent
      variables by sex. In men, deprivation (OR 1.85, 95 % CI 1.54-2.17), being
      divorced (OR 2.34, 95 % CI 1.61-3.39) or widowed (OR 3.64, 95 % CI 2.40-5.52),
      physical inactivity (OR 1.30, 95 % CI 1.02-1.65), having a history of spine and
      joint disease (OR 1.72, 95 % CI 1.36-2.17), average perceived health (OR 2.14, 95
      % CI 1.55-2.95), poor perceived health (OR 5.13, 95 % CI 3.39-7.76), average
      quality of life (OR 2.0, 95 % CI 1.55-2.95), or poor quality of life (OR 8.86, 95
      % CI 5.19-15.13) were significantly associated with depressive symptoms. In
      women, deprivation (OR 1.28, 95 % CI 1.15-1.43), being widowed (OR 1.52, 95 % CI
      1.23-1.88), mean dose of alcohol per occasion 40-79.9 g (OR 1.65, 95 % CI 1.18
      2.30) and more than 80 g (OR 2.09, 95 % CI 1.14-3.82), physical inactivity in
      leisure time (OR 1.27, 95 % CI 1.04-1.57), having a history of spine and joint
      disease (OR 1.26, 95 % CI 1.06-1.51), average perceived health (OR 2.56, 95 % CI
      1.89-2.72), poor perceived health (OR 5.07, 95 % CI 3.62-7.11), average quality
      of life (OR 2.27, 95 % CI 1.89-2.72), or poor quality of life (OR 7.21, 95 % CI
      4.73-11.00) were significantly associated with depressive symptoms. CONCLUSIONS:
      Health status and lifestyle factors are associated with depressive symptoms.
      Associations between depressive symptoms and long-term health problems are
      partially mediated by self-rated quality of life and self-rated health.

PMID- 24570205
TI  - Special section guest editorial: Optical coherence tomography and interferometry:
      advanced engineering and biomedical applications.

PMID- 24570203
TI  - Service use in adolescents at risk of depression and self-harm: prospective
      longitudinal study.
AB  - PURPOSE: Although depression and self-harm are common mental health problems in
      adolescents, there are barriers to accessing help. Using a community-based
      sample, this study investigates predictors of service contacts for adolescents at
      high risk of depression and self-harm. METHODS: Three thousand seven hundred and
      forty-nine (3,749) 12- to 16-year-olds in UK secondary (high) schools provided
      baseline and 6 months' follow-up data on mood, self-harm and service contacts
      with a range of primary and secondary healthcare services. RESULTS: Although most
      adolescents at high risk of depression or self-harm had seen their general
      practitioner (GP) in the previous 6 months, less than one-third had used primary
      or secondary healthcare services for emotional problems. 5 % of adolescents who
      reported self-harm had seen specialist child and adolescent mental health
      services in the previous 6 months. In longitudinal analyses, after adjustment for
      confounders, both depression and self-harm predicted the use of any healthcare
      services [adjusted odds ratio (AOR) = 1.34 (95 % CI 1.09, 1.64); AOR = 1.38 (95 %
      CI 1.02, 1.86), respectively] and of specialist mental health services [AOR =
      5.48 (95 % CI 2.27, 13.25); AOR = 2.58 (95 % CI 1.11, 6.00), respectively].
      Amongst those with probable depression, 79 % had seen their GP and 5 % specialist
      mental health services in the preceding year. CONCLUSIONS: Most adolescents at
      high risk of depression or self-harm see their GP over a 6-month period although
      only a minority of them access specialist mental health services. Their
      consultations within primary care settings provide a potential opportunity for
      their identification and for signposting to appropriate specialist services.

PMID- 24570206
TI  - Modulation transfer function assessment in parallel beam and fan beam collimators
      with square and cylindrical holes.
AB  - OBJECTIVE: This study investigates modulation transfer function (MTF) in parallel
      beam (PB) and fan beam (FB) collimators using the Monte Carlo method with full
      width at half maximum (FWHM), square and circular-shaped holes, and scatter and
      penetration (S + P) components. METHODS: A regulation similar to the lead-to-air
      ratio was used for both collimators to estimate output data. The hole pattern was
      designed to compare FB by PB parameters. The radioactive source in air and in a
      water phantom placed in front of the collimators was simulated using MCNP5 code.
      RESULTS: The test results indicated that the square holes in PB (PBs) had better
      FWHM than did the cylindrical (PBc) holes. In contrast, the cylindrical holes in
      the FB (FBc) had better FWHM than the square holes. In general, the resolution of
      FBc was better than that of the PBc in air and scatter mediums. The S + P
      decreased for all collimators as the distance from the source to the collimator
      surface (z) increased. The FBc had a lower S + P than FBs, but PBc had a higher S
      + P than PBs. Of the FB and PB collimators with the identical hole shapes, PBs
      had a smaller S + P than FBs, and FBc had a smaller S + P than PBc. The MTF value
      for the FB was greater than for the PB and had increased spatial frequency; the
      FBc had higher MTF than the FBs and PB collimators. CONCLUSIONS: Estimating the
      FB using PB parameters and diverse hole shapes may be useful in collimator design
      to improve the resolution and efficiency of SPECT images.

PMID- 24570204
TI  - Sexual orientation disparities in mental health: the moderating role of
      educational attainment.
AB  - PURPOSE: Mental health disparities between sexual minorities and heterosexuals
      remain inadequately understood, especially across levels of educational
      attainment. The purpose of the present study was to test whether education
      modifies the association between sexual orientation and mental disorder. METHODS:
      We compared the odds of past 12-month and lifetime psychiatric disorder
      prevalence (any Axis-I, any mood, any anxiety, any substance use, and
      comorbidity) between lesbian, gay, and bisexual (LGB) and heterosexual
      individuals by educational attainment (those with and without a bachelor's
      degree), adjusting for covariates, and tested for interaction between sexual
      orientation and educational attainment. Data are drawn from the National
      Epidemiologic Survey on Alcohol and Related Conditions, a nationally
      representative survey of non-institutionalized US adults (N = 34,653; 577 LGB).
      RESULTS: Sexual orientation disparities in mental health are smaller among those
      with a college education. Specifically, the disparity in those with versus those
      without a bachelor's degree was attenuated by 100 % for any current mood
      disorder, 82 % for any current Axis-I disorder, 76 % for any current anxiety
      disorder, and 67 % for both any current substance use disorder and any current
      comorbidity. Further, the interaction between sexual orientation and education
      was statistically significant for any current Axis-I disorder, any current mood
      disorder, and any current anxiety disorder. Our findings for lifetime outcomes
      were similar. CONCLUSIONS: The attenuated mental health disparity at higher
      education levels underscores the particular risk for disorder among LGBs with
      less education. Future studies should consider selection versus causal factors to
      explain the attenuated disparity we found at higher education levels.

PMID- 24570208
TI  - Analysis of cell concentration, volume concentration, and colony size of
      Microcystis via laser particle analyzer.
AB  - The analysis of the cell concentration, volume concentration, and colony size of
      Microcystis is widely used to provide early warnings of the occurrence of blooms
      and to facilitate the development of predictive tools to mitigate their impact.
      This study developed a new approach for the analysis of the cell concentration,
      volume concentration, and colony size of Microcystis by applying a laser particle
      analyzer. Four types of Microcystis samples (55 samples in total) were analyzed
      by a laser particle analyzer and a microscope. By the application of the laser
      particle analyzer (1) when n = 1.40 and k = 0.1 (n is the intrinsic refractive
      index, whereas k is absorption of light by the particle), the results of the
      laser particle analyzer showed good agreement with the microscopic results for
      the obscuration indicator, volume concentration, and size distribution of
      Microcystis; (2) the Microcystis cell concentration can be calculated based on
      its linear relationship with obscuration; and (3) the volume concentration and
      size distribution of Microcystis particles (including single cells and colonies)
      can be obtained. The analytical processes involved in this new approach are
      simpler and faster compared to that by microscopic counting method. From the
      results, it was identified that the relationship between cell concentration and
      volume concentration depended on the colony size of Microcystis because the
      intercellular space was high when the colony size was high. Calculation of cell
      concentration and volume concentration may occur when the colony size information
      is sufficient. 

PMID- 24570207
TI  - Genome-wide association study for age-related hearing loss (AHL) in the mouse: a
      meta-analysis.
AB  - Age-related hearing loss (AHL) is characterized by a symmetric sensorineural
      hearing loss primarily in high frequencies and individuals have different levels
      of susceptibility to AHL. Heritability studies have shown that the sources of
      this variance are both genetic and environmental, with approximately half of the
      variance attributable to hereditary factors as reported by Huag and Tang (Eur
      Arch Otorhinolaryngol 267(8):1179-1191, 2010). Only a limited number of large
      scale association studies for AHL have been undertaken in humans, to date. An
      alternate and complementary approach to these human studies is through the use of
      mouse models. Advantages of mouse models include that the environment can be more
      carefully controlled, measurements can be replicated in genetically identical
      animals, and the proportion of the variability explained by genetic variation is
      increased. Complex traits in mouse strains have been shown to have higher
      heritability and genetic loci often have stronger effects on the trait compared
      to humans. Motivated by these advantages, we have performed the first genome-wide
      association study of its kind in the mouse by combining several data sets in a
      meta-analysis to identify loci associated with age-related hearing loss. We
      identified five genome-wide significant loci (<10(-6)). One of these loci
      confirmed a previously identified locus (ahl8) on distal chromosome 11 and
      greatly narrowed the candidate region. Specifically, the most significant
      associated SNP is located 450 kb upstream of Fscn2. These data confirm the
      utility of this approach and provide new high-resolution mapping information
      about variation within the mouse genome associated with hearing loss.

PMID- 24570209
TI  - Immunohistochemistry for BRAF(V600E) antibody VE1 performed in core needle biopsy
      samples identifies mutated papillary thyroid cancers.
AB  - BRAF(V600E) is the most frequent genetic mutation in papillary thyroid cancer
      (PTC) and has been reported as an independent predictor of poor prognosis of
      these patients. Current guidelines do not recommend the use of BRAF(V600E)
      mutational analysis on cytologic specimens from fine needle aspiration due to
      several reasons. Recently, immunohistochemistry using VE1, a mouse anti-human
      BRAF(V600E) antibody, has been reported as a highly reliable technique in
      detecting BRAF-mutated thyroid and nonthyroid cancers. The aim of this study was
      to test the reliability of VE1 immunohistochemistry on microhistologic samples
      from core needle biopsy (CNB) in identifying BRAF-mutated PTC. A series of 30
      nodules (size ranging from 7 to 22 mm) from 30 patients who underwent surgery
      following CNB were included in the study. All these lesions had had inconclusive
      cytology. In all cases, both VE1 and BRAF(V600E) genotypes were evaluated. After
      surgery, final histology demonstrated 21 cancers and 9 benign lesions. CNB
      correctly diagnosed 20/20 PTC and 5/5 adenomatous nodules. One follicular thyroid
      cancer and 4 benign lesions were assessed at CNB as uncertain follicular
      neoplasm. VE1 immunohistochemistry revealed 8 mutated PTC and 22 negative cases.
      A 100% agreement was found when positive and negative VE1 results were compared
      with BRAF mutational status. These data are the first demonstration that VE1
      immunohistochemistry performed on thyroid CNB samples perfectly matches with
      genetic analysis of BRAF status. Thus, VE1 antibody can be used on thyroid
      microhistologic specimens to detect BRAF(V600E)-mutated PTC before surgery. 

PMID- 24570210
TI  - Social network analysis of multi-level linkages: a Swedish case study on Northern
      Forest-Based sectors.
AB  - Forest use in Northern Sweden is being influenced both by global trends and local
      situations. This results in interactions between numerous groups that may impact
      local forest governance. Social network analysis can here provide insight into
      the total pattern of positive, negative, and cross-level interactions within user
      group community structure (within and among groups). This study analyses
      interactions within selected renewable resource sectors in two northern Swedish
      municipalities, both with regard to whether they are positive, neutral, or
      negative, as well as with regard to how local actors relate to actors across
      levels, e.g., with regional, national, and international actors. The study
      illustrates that many interactions both within and outside a given sector are
      seen as neutral or positive, and that considerable interaction and impact are
      defined as national and in some cases even international. It also indicates that
      the impact of Sweden's only existing Model Forest may to some extent constitute a
      bridge between different sectors and levels, in comparison with the interactions
      between sectors in a municipality where such a cooperation mechanism does not
      exist. 

PMID- 24570211
TI  - Climate change and forest communities: prospects for building institutional
      adaptive capacity in the Congo Basin forests.
AB  - Tropical forests are vulnerable to climate-change representing a risk for
      indigenous peoples and forest-dependent communities. Mechanisms to conserve the
      forest, such as REDD+, could assist in the mitigation of climate change, reduce
      vulnerability, and enable people to adapt. Ninety-eight interviews were conducted
      in three countries containing the Congo Basin forest, Cameroon, CAR, and DRC, to
      investigate perceptions of decision-makers within, and responses of the
      institutions of the state, private sector, and civil society to the challenges of
      climate change. Results indicate that while decision-makers' awareness of climate
      change is high, direct institutional action is at an early stage. Adaptive
      capacity is currently low, but it could be enhanced with further development of
      institutional linkages and increased coordination of multilevel responses across
      all institutions and with local people. It is important to build networks with
      forest-dependent stakeholders at the local level, who can contribute knowledge
      that will build overall institutional adaptive capacity. 

PMID- 24570212
TI  - Mercury in precipitation at an urbanized coastal zone of the Baltic Sea (Poland).
AB  - Wet deposition is an important source of metals to the sea. The temporal
      variability of Hg concentrations in precipitation, and the impact of air masses
      of different origins over the Polish coastal zone were assessed. Samples of
      precipitation were collected (August 2008-May 2009) at an urbanized coastal
      station in Poland. Hg analyses were conducted using CVAFS. These were the first
      measurements of Hg concentration in precipitation obtained in the Polish coastal
      zone. Since Poland was identified as the biggest emitter of Hg to the Baltic,
      these data are very important. In the heating and non-heating season, Hg
      concentrations in precipitation were similar. Hg wet deposition flux dominated in
      summer, when the production of biomass in the aquatic system was able to actively
      adsorb Hg. Input of metal to the sea was attributed to regional and distant
      sources. Maritime air masses, through transformation of Hg(0), were an essential
      vector of mercury in precipitation. 

PMID- 24570213
TI  - Water planning and hydro-climatic change in the Murray-Darling Basin, Australia.
AB  - More than a third of humanity lives in regions with less than 1 million liters of
      fresh water per person per year. Population growth will increase water demand
      while climate change in arid and semi-arid areas may reduce water availability.
      The Murray-Darling Basin in Australia is a region where water reform and planning
      have been used to reduce consumptive extraction to better sustain river
      ecosystems under climate variability. Using actual data and previously published
      models that account for climate variability and climate change, the trade-off
      between water extractions and water essential to the long-term ecological
      function of river systems is analysed. The findings indicate that better water
      planning and a more complete understanding of the effects of irrigation on
      regional climate evapotranspiration could: (1) increase the overall benefits of
      consumptive and non-consumptive water use; (2) improve riparian environments
      under climate variability; and (3) be achieved with only small effects on the
      profits and gross value of food and fiber production.

PMID- 24570214
TI  - Mechanisms of association between physical functioning and breast cancer
      mortality: evidence from the Women's Healthy Eating and Living Study.
AB  - PURPOSE: Low physical functioning among breast cancer survivors appears to reduce
      survival, although the mechanisms underlying these associations are not clear. We
      examined inflammation as a possible biological mediator of association between
      low physical functioning and mortality after breast cancer. METHODS: Analysis
      included 2,892 participants from the Women's Healthy Eating and Living Study. All
      measures were collected at study baseline. Physical function was assessed by the
      Short Form 36 (SF-36) Health Survey Physical Function subscale. Low physical
      function was defined as the bottom tertile of the subscale score. Inflammation
      was measured as serum concentration of C-reactive protein (CRP). Cox proportional
      hazards modeled the associations of low physical function and the putative
      mediator (i.e., CRP) with all-cause and breast cancer-specific mortality.
      RESULTS: There were 293 deaths during study follow up, with 243 due to breast
      cancer. Low physical functioning was associated with a 50 % higher risk of all
      cause mortality (HR, 1.49; 95 % CI, 1.2-1.9) and a 40 % higher risk of breast
      cancer-specific mortality (HR, 1.39; 95 % CI, 1.1-1.8), after adjustment for
      covariates. The addition of CRP did not markedly change the all-cause mortality
      hazard ratio attributed to low physical functioning. However, the addition of CRP
      modestly attenuated the breast cancer-specific mortality hazard ratio such that
      it was no longer statistically significant. CONCLUSIONS: Interventions to improve
      physical functioning may prevent early morbidity and mortality among breast
      cancer survivors. IMPLICATIONS FOR CANCER SURVIVORS: Functional status measure
      may be a valuable indicator of long-term health outcomes among breast cancer
      survivors.

PMID- 24570215
TI  - Determinants of newly diagnosed comorbidities among breast cancer survivors.
AB  - PURPOSE: Comorbid conditions have become increasingly relevant for breast cancer
      care given the large numbers of long-term survivors. Our aim was to identify
      potential determinants associated with the development of comorbidities after
      breast cancer. METHODS: Self-reported comorbidities and lifestyle were assessed
      at recruitment and after a median follow up of 69.4 months from diagnosis in a
      population-based cohort of breast cancer cases aged 50 to 74 years at diagnosis
      (MARIEplus study). Tumor and therapy data were extracted from medical records.
      Determinants potentially associated with incident diagnoses of hypertension,
      cardiovascular diseases (CVD), and osteoporosis were assessed using multivariable
      Cox proportional hazard regression models. RESULTS: Follow-up interview was
      completed by 2,542 women (76.4 % of eligible patients). A diagnosis of
      hypertension was significantly associated with age, higher education (hazard
      ratio (HR) 0.54, CI 0.37-0.79), baseline body mass index (BMI; >=30 kg/m(2); HR,
      1.90; CI, 1.24-2.90), and trastuzumab medication (HR, 2.16; CI, 1.09-4.33). An
      increased risk for CVD was associated with age, BMI, and intake of aromatase
      inhibitors (AI; HR, 1.42; CI, 1.09-1.84). Risk of osteoporosis was also
      positively associated with AI treatment (HR, 2.15; CI, 1.64-2.82) but inversely
      associated with a higher BMI (>=30 kg/m(2); HR, 0.50; CI, 0.31-0.79). CONCLUSION:
      In breast cancer survivors, treatment with AI constituted a risk factor for
      incident CVD and osteoporosis. Besides known risk factors, patients who were
      treated with trastuzumab may have an increased risk for hypertension.
      IMPLICATIONS FOR CANCER SURVIVORS: Reducing overweight and regular sport/cycling
      activities may help to prevent CVD after breast cancer. Patients should be
      monitored for risk factors and advised on possible cardiac side effects of AI and
      trastuzumab.

PMID- 24570216
TI  - Unmet information and support needs in newly diagnosed thyroid cancer: comparison
      of adolescents/young adults (AYA) and older patients.
AB  - PURPOSE: Thyroid cancer (TC) is the most common cancer in adolescent and young
      adult (AYA) females ages 15-29 and second for 30-39. However, little research
      details the unmet support needs and survivorship concerns of TC patients.
      METHODS: TC patients >=15 years of age at diagnosis completed online surveys
      through the thyroid cancer survivor (ThyCa) website. Survivors rated the
      importance of medical/physical (M/Ph), practical, and emotional/psychological
      (E/Ps) realms of information during diagnosis and treatment, as well as
      recollection of receiving such information. Comparison was made between AYAs and
      those >=40 years at diagnosis. RESULTS: Of 1,113 respondents, most were female
      (88.3 %), part Caucasian (92.3 %), and treated in academic or private urban
      settings. More than 80 % of patients rated receiving information about most M/Ph
      matters very or extremely important and >70 % for most E/Ps concerns. However,
      few recalled receiving any information besides the surrounding surgery and
      radioiodine (RAI). AYAs were more often female, non-white, Hispanic, married with
      children, living with a spouse/significant other, and unemployed at diagnosis (p
      < 0.001). Significant differences were noted in the importance AYAs placed on
      many M/Ph and practical matters, but not E/Ps ones. AYAs less commonly recalled
      receiving information on recurrence (p = 0.038), long-term side effects (p =
      0.024), coping strategies (p = 0.049), support groups (p = 0.019), opportunities
      for meeting other survivors (p = 0.009), or help with treatment decisions (p =
      0.036); they reported receiving less overall care for E/Ps concerns (p = 0.016).
      CONCLUSION: TC patients place high importance on receiving information regarding
      most aspects of TC treatment and survivorship care. However, these information
      needs and survivorship concerns are largely unmet, especially among AYAs.
      IMPLICATIONS FOR CANCER SURVIVORS: Participating in multidisciplinary and
      survivorship-focused TC care may alleviate some of these unmet information and
      support needs.

PMID- 24570217
TI  - Efficacy and feasibility of a tele-health intervention for acute coronary
      syndrome patients with depression: results of the "MoodCare" randomized
      controlled trial.
AB  - BACKGROUND: Depression is common after a cardiac event, yet there remain few
      approaches to management that are both effective and scalable. PURPOSE: We aimed
      to evaluate the 6-month efficacy and feasibility of a tele-health program
      (MoodCare) that integrates depression management into a cardiovascular disease
      risk reduction program for acute coronary syndrome patients with low mood.
      METHODS: A two-arm, parallel, randomized design was used comprising 121 patients
      admitted to one of six hospitals for acute coronary syndrome. RESULTS:
      Significant treatment effects were observed for Patient Health Questionnaire 9
      (PHQ9) depression (mean difference [change] = -1.8; p = 0.025; effect size: d =
      0.36) for the overall sample, when compared with usual medical care. Results were
      more pronounced effects for those with a history of depression (mean difference
      [change] = -2.7; p = 0.043; effect size: d = 0.65). CONCLUSIONS: MoodCare was
      effective for improving depression in acute coronary syndrome patients, producing
      effect sizes exceeding those of some face-to-face psychotherapeutic interventions
      and pharmacotherapy. ( TRIAL REGISTRATION NUMBER: ACTRN1260900038623.).

PMID- 24570219
TI  - Nutrient-specific perceptions of food healthiness and the role of nutrition
      knowledge: a comment on Rizk and Treat.

PMID- 24570218
TI  - Divergent associations of antecedent- and response-focused emotion regulation
      strategies with midlife cardiovascular disease risk.
AB  - BACKGROUND: It is not known whether various forms of emotion regulation are
      differentially related to cardiovascular disease risk. PURPOSE: The purpose of
      this study is to assess whether antecedent and response-focused emotion
      regulation would have divergent associations with likelihood of developing
      cardiovascular disease. METHODS: Two emotion regulation strategies were examined:
      reappraisal (antecedent-focused) and suppression (response-focused).
      Cardiovascular disease risk was assessed with a validated Framingham algorithm
      that estimates the likelihood of developing CVD in 10 years. Associations were
      assessed among 373 adults via multiple linear regression. Pathways and gender
      specific associations were also considered. RESULTS: One standard deviation
      increases in reappraisal and suppression were associated with 5.9 % lower and
      10.0 % higher 10-year cardiovascular disease risk, respectively, in adjusted
      analyses. CONCLUSIONS: Divergent associations of antecedent and response-focused
      emotion regulation with cardiovascular disease risk were observed. Effective
      emotion regulation may promote cardiovascular health.

PMID- 24570220
TI  - Beliefs about medicines in 3D: a comment on Phillips et al.

PMID- 24570222
TI  - Involuntary detention: do psychiatrists clinically justify continuing involuntary
      hospitalization?
AB  - To elucidate disparities in clinical and legal documentation for patients
      admitted involuntarily to a county psychiatric hospital in Texas. The study
      sample comprised of 89 randomly selected patients, involuntarily hospitalized to
      our facility in September 2011. All patients met criteria for involuntary
      detention based on the legal documents filed by admitting psychiatrists.
      Electronic medical records were reviewed to assess if the clinical documentation
      from the same date when legal documents were filed; demonstrated criteria for
      involuntary detention (harm to self, harm to others, inability to care for self).
      A logistic regression model was used to assess the predictors of concordance
      between legal and clinical documentation of involuntary detention criteria. Of
      89, 6 patients were made voluntary, while two were discharged within 24 h, thus
      removed from the analysis pool. Of 81, 31(38.2 %) patients lacked sufficient
      clinical documentation on medical records required for involuntary
      hospitalization. Patients, for whom detention was justified in clinical notes,
      were more likely to have single marital status, longer duration of
      hospitalization and they were more likely to undergo commitment for further
      inpatient mental health treatment. Our study found that involuntary detention of
      many patients based on the legal documents filed by admitting psychiatrists was
      not justified by the clinical documentation. This indicates that appropriate
      standards are not maintained when completing the medical certificates for
      involuntary detention. Maintaining appropriate standards may reduce the need for
      involuntary hospitalization, increase patient autonomy, and reduce resource
      utilization.

PMID- 24570225
TI  - February Thaw: Charles Burchfield.

PMID- 24570226
TI  - Time to hang up the white coat? Epidemiologists suggest ways to prevent clothing
      from spreading infection.

PMID- 24570227
TI  - Demonstration projects in Vietnam and Uganda show global health security begins
      at the local level.

PMID- 24570221
TI  - The implementation of life space crisis intervention in residential care and
      special education for children and adolescents with EBD: an effect study.
AB  - When working with children and adolescents with emotional and behavioural
      disorders, conflicts are a part of daily life. At present, a variety of conflict
      resolution or conflict management programs, that can be divided into three
      categories, are described in the literature. A first category contains programs
      that focus on training for children and adolescents, and are often curriculum
      based. The second category focuses on training for parents, and the third
      category contains programs that focus on training for professionals. The presents
      study was designed to evaluated the effectiveness of Life Space Crisis
      Intervention (LSCI), a therapeutic and verbal strategy developed by Long that
      fits into this third category of conflict management programs. Throughout a four
      year project, al staff in a Flemish centre offering residential care and special
      education were trained in LSCI. On a yearly basis, data with regard to time in
      program, academic achievement, behavioural problems and anxiety problems were
      collected. The results show an increase in time spent in program and in academic
      achievement, and a decrease in youths' anxiety, indicating that the
      implementation of LSCI contributes constructively to the treatment of children
      and adolescents with EBD.

PMID- 24570240
TI  - A unified code of ethics for health professionals: insights from an IOM workshop.

PMID- 24570241
TI  - A piece of my mind. Adverbs.

PMID- 24570242
TI  - The patient-centered medical home: one size does not fit all.

PMID- 24570243
TI  - Nonspecific effects of vaccines.

PMID- 24570244
TI  - Prevalence of childhood and adult obesity in the United States, 2011-2012.
AB  - IMPORTANCE: More than one-third of adults and 17% of youth in the United States
      are obese, although the prevalence remained stable between 2003-2004 and 2009
      2010. OBJECTIVE: To provide the most recent national estimates of childhood
      obesity, analyze trends in childhood obesity between 2003 and 2012, and provide
      detailed obesity trend analyses among adults. DESIGN, SETTING, AND PARTICIPANTS:
      Weight and height or recumbent length were measured in 9120 participants in the
      2011-2012 nationally representative National Health and Nutrition Examination
      Survey. MAIN OUTCOMES AND MEASURES: In infants and toddlers from birth to 2
      years, high weight for recumbent length was defined as weight for length at or
      above the 95th percentile of the sex-specific Centers for Disease Control and
      Prevention (CDC) growth charts. In children and adolescents aged 2 to 19 years,
      obesity was defined as a body mass index (BMI) at or above the 95th percentile of
      the sex-specific CDC BMI-for-age growth charts. In adults, obesity was defined as
      a BMI greater than or equal to 30. Analyses of trends in high weight for
      recumbent length or obesity prevalence were conducted overall and separately by
      age across 5 periods (2003-2004, 2005-2006, 2007-2008, 2009-2010, and 2011-2012).
      RESULTS: In 2011-2012, 8.1% (95% CI, 5.8%-11.1%) of infants and toddlers had high
      weight for recumbent length, and 16.9% (95% CI, 14.9%-19.2%) of 2- to 19-year
      olds and 34.9% (95% CI, 32.0%-37.9%) of adults (age-adjusted) aged 20 years or
      older were obese. Overall, there was no significant change from 2003-2004 through
      2011-2012 in high weight for recumbent length among infants and toddlers, obesity
      in 2- to 19-year-olds, or obesity in adults. Tests for an interaction between
      survey period and age found an interaction in children (P = .03) and women (P =
      .02). There was a significant decrease in obesity among 2- to 5-year-old children
      (from 13.9% to 8.4%; P = .03) and a significant increase in obesity among women
      aged 60 years and older (from 31.5% to 38.1%; P = .006). CONCLUSIONS AND
      RELEVANCE: Overall, there have been no significant changes in obesity prevalence
      in youth or adults between 2003-2004 and 2011-2012. Obesity prevalence remains
      high and thus it is important to continue surveillance.

PMID- 24570245
TI  - Association between participation in a multipayer medical home intervention and
      changes in quality, utilization, and costs of care.
AB  - IMPORTANCE: Interventions to transform primary care practices into medical homes
      are increasingly common, but their effectiveness in improving quality and
      containing costs is unclear. OBJECTIVE: To measure associations between
      participation in the Southeastern Pennsylvania Chronic Care Initiative, one of
      the earliest and largest multipayer medical home pilots conducted in the United
      States, and changes in the quality, utilization, and costs of care. DESIGN,
      SETTING, AND PARTICIPANTS: Thirty-two volunteering primary care practices
      participated in the pilot (conducted from June 1, 2008, to May 31, 2011). We
      surveyed pilot practices to compare their structural capabilities at the pilot's
      beginning and end. Using claims data from 4 participating health plans, we
      compared changes (in each year, relative to before the intervention) in the
      quality, utilization, and costs of care delivered to 64,243 patients who were
      attributed to pilot practices and 55,959 patients attributed to 29 comparison
      practices (selected for size, specialty, and location similar to pilot practices)
      using a difference-in-differences design. EXPOSURES: Pilot practices received
      disease registries and technical assistance and could earn bonus payments for
      achieving patient-centered medical home recognition by the National Committee for
      Quality Assurance (NCQA). MAIN OUTCOMES AND MEASURES: Practice structural
      capabilities; performance on 11 quality measures for diabetes, asthma, and
      preventive care; utilization of hospital, emergency department, and ambulatory
      care; standardized costs of care. RESULTS: Pilot practices successfully achieved
      NCQA recognition and adopted new structural capabilities such as registries to
      identify patients overdue for chronic disease services. Pilot participation was
      associated with statistically significantly greater performance improvement,
      relative to comparison practices, on 1 of 11 investigated quality measures:
      nephropathy screening in diabetes (adjusted performance of 82.7% vs 71.7% by year
      3, P < .001). Pilot participation was not associated with statistically
      significant changes in utilization or costs of care. Pilot practices accumulated
      average bonuses of $92,000 per primary care physician during the 3-year
      intervention. CONCLUSIONS AND RELEVANCE: A multipayer medical home pilot, in
      which participating practices adopted new structural capabilities and received
      NCQA certification, was associated with limited improvements in quality and was
      not associated with reductions in utilization of hospital, emergency department,
      or ambulatory care services or total costs over 3 years. These findings suggest
      that medical home interventions may need further refinement.

PMID- 24570246
TI  - Live vaccine against measles, mumps, and rubella and the risk of hospital
      admissions for nontargeted infections.
AB  - IMPORTANCE: In low-income countries, live measles vaccine reduces mortality from
      causes other than measles infection. Such nonspecific effects of vaccines might
      also be important for the health of children in high-income settings. OBJECTIVE:
      To examine whether the live vaccine against measles, mumps, and rubella (MMR) is
      associated with lower rates of hospital admissions for infections among children
      in Denmark. DESIGN, SETTING, AND PARTICIPANTS: Population-based cohort study of
      Danish children born 1997-2006 and followed up from ages 11 months to 2 years
      (last follow-up, August 31, 2008). Nationwide Danish registers provided data on
      vaccinations and hospital admissions. The recommended vaccination schedule was
      inactivated vaccine against diphtheria, tetanus, pertussis, polio, and
      Haemophilus influenzae type b (DTaP-IPV-Hib) administered at ages 3, 5, and 12
      months and MMR at age 15 months. MAIN OUTCOMES AND MEASURES: Incidence rate
      ratios (IRRs) of hospital admissions for any infection, comparing receipt of MMR
      vs DTaP-IPV-Hib as the most recent vaccine. Risks, risk difference, and number
      needed to vaccinate were calculated for receiving MMR on time. RESULTS: The study
      included 495,987 children contributing with 56,889 hospital admissions for any
      type of infection during 509,427 person-years (rate, 11.2 per 100 person-years).
      For the 456,043 children who followed the recommended schedule and received MMR
      after the third dose of DTaP-IPV-Hib, MMR (rate, 8.9 per 100 person-years) vs the
      third dose of DTaP-IPV-Hib (rate, 12.4 per 100 person-years) as the most recent
      vaccine was associated with an adjusted IRR of 0.86 (95% CI, 0.84-0.88) for any
      admission for infection. There were 19,219 children immunized out of sequence.
      The adjusted IRR was 0.87 (95% CI, 0.80-0.95) for those receiving MMR (rate, 9.9
      per 100 person-years) after the second dose of DTaP-IPV-Hib (rate, 15.1 per 100
      person-years). However, in the 1981 children who subsequently received the third
      dose of DTaP-IPV-Hib (rate, 12.8 per 100 person-years) after MMR, the IRR for
      hospital admissions for infection was significantly greater (adjusted IRR, 1.62
      [95% CI, 1.28-2.05]). The risk of admission for an infection between ages 16
      months and 24 months was 4.6% (95% CI, 4.5%-4.7%) for receiving MMR on time and
      5.1% (95% CI, 5.0%-5.2%) for not receiving MMR on time. The risk difference was
      0.5 percentage point (95% CI, 0.4-0.6), and the number needed to vaccinate with
      MMR before age 16 months to prevent 1 admission for any infection was 201 (95%
      CI, 159-272). CONCLUSIONS AND RELEVANCE: In a cohort of Danish children, receipt
      of live MMR vs inactivated DTaP-IPV-Hib as the most recent vaccine was associated
      with a lower rate of hospital admissions for any infections. These findings
      require replication in other high-income populations.

PMID- 24570247
TI  - Patterns and outcomes of red blood cell transfusion in patients undergoing
      percutaneous coronary intervention.
AB  - IMPORTANCE: Studies have shown variation in the use of red blood cell transfusion
      among patients with acute coronary syndromes. There are no definitive data for
      the efficacy of transfusion in improving outcomes, and concerning data exist
      about possible association with harm. Current transfusion practices in patients
      undergoing percutaneous coronary intervention (PCI) are not well understood.
      OBJECTIVE: To determine the current patterns of blood transfusion among patients
      undergoing PCI and the association of transfusion with adverse cardiac outcomes
      across hospitals in the United States. DESIGN, SETTING, AND PARTICIPANTS:
      Retrospective cohort study of all patient visits from the CathPCI Registry from
      July 2009 to March 2013 that included PCI, excluding those with missing data on
      bleeding complications or who underwent in-hospital coronary artery bypass graft
      surgery (N = 2,258,711 visits). MAIN OUTCOMES AND MEASURES: Transfusion rates in
      the overall population and by hospital (N = 1431) were the primary outcomes. The
      association of transfusion with myocardial infarction, stroke, and death after
      accounting for a patient's propensity for transfusion was also measured. RESULTS:
      The overall rate of transfusion was 2.14% (95% CI, 2.13%-2.16%) and quarterly
      transfusion rates slightly declined from July 2009 to March 2013 (from 2.11% [95%
      CI, 2.03%-2.19%] to 2.04% [95% CI, 1.97%-2.12%]; P < .001). Patients who were
      more likely to receive transfusion were older (mean, 70.5 vs 64.6 years), were
      women (56.3% vs 32.5%), and had hypertension (86.4% vs 82.0%), diabetes (44.8% vs
      34.6%), advanced renal dysfunction (8.7% vs 2.3%), prior myocardial infarction
      (33.0% vs 30.2%), or prior heart failure (27.0% vs 11.8%). Overall, 96.3% of
      sites gave a transfusion to less than 5% of patients and 3.7% of sites gave a
      transfusion to 5% of patients or more. Variation in hospital risk-standardized
      rates of transfusion persisted after adjustment, and hospitals showed variability
      in their transfusion thresholds. Receipt of transfusion was associated with
      myocardial infarction (42,803 events; 4.5% vs 1.8%; odds ratio [OR], 2.60; 95%
      CI, 2.57-2.63), stroke (5011 events; 2.0% vs 0.2%; OR, 7.72; 95% CI, 7.47-7.98),
      and in-hospital death (31,885 events; 12.5% vs 1.2%; OR, 4.63; 95% CI, 4.57
      4.69), irrespective of bleeding complications. CONCLUSIONS AND RELEVANCE: Among
      patients undergoing PCI at US hospitals, there was considerable variation in
      blood transfusion practices, and receipt of transfusion was associated with
      increased risk of in-hospital adverse cardiac events. These observational
      findings may warrant a randomized trial of transfusion strategies for patients
      undergoing PCI.

PMID- 24570249
TI  - Drugs for urinary tract infections.

PMID- 24570250
TI  - Handling of thermal receipts as a source of exposure to bisphenol A.

PMID- 24570251
TI  - Next-day surgical complications after nighttime procedures.

PMID- 24570248
TI  - Urinary tract infections in older women: a clinical review.
AB  - IMPORTANCE: Asymptomatic bacteriuria and symptomatic urinary tract infections
      (UTIs) in older women are commonly encountered in outpatient practice. OBJECTIVE:
      To review management of asymptomatic bacteriuria and symptomatic UTI and review
      prevention of recurrent UTIs in older community-dwelling women. EVIDENCE REVIEW:
      A search of Ovid (Medline, PsycINFO, Embase) for English-language human studies
      conducted among adults aged 65 years and older and published in peer-reviewed
      journals from 1946 to November 20, 2013. RESULTS: The clinical spectrum of UTIs
      ranges from asymptomatic bacteriuria, to symptomatic and recurrent UTIs, to
      sepsis associated with UTI requiring hospitalization. Recent evidence helps
      differentiate asymptomatic bacteriuria from symptomatic UTI. Asymptomatic
      bacteriuria is transient in older women, often resolves without any treatment,
      and is not associated with morbidity or mortality. The diagnosis of symptomatic
      UTI is made when a patient has both clinical features and laboratory evidence of
      a urinary infection. Absent other causes, patients presenting with any 2 of the
      following meet the clinical diagnostic criteria for symptomatic UTI: fever,
      worsened urinary urgency or frequency, acute dysuria, suprapubic tenderness, or
      costovertebral angle pain or tenderness. A positive urine culture (>=105 CFU/mL)
      with no more than 2 uropathogens and pyuria confirms the diagnosis of UTI. Risk
      factors for recurrent symptomatic UTI include diabetes, functional disability,
      recent sexual intercourse, prior history of urogynecologic surgery, urinary
      retention, and urinary incontinence. Testing for UTI is easily performed in the
      clinic using dipstick tests. When there is a low pretest probability of UTI, a
      negative dipstick result for leukocyte esterase and nitrites excludes infection.
      Antibiotics are selected by identifying the uropathogen, knowing local resistance
      rates, and considering adverse effect profiles. Chronic suppressive antibiotics
      for 6 to 12 months and vaginal estrogen therapy effectively reduce symptomatic
      UTI episodes and should be considered in patients with recurrent UTIs.
      CONCLUSIONS AND RELEVANCE: Establishing a diagnosis of symptomatic UTI in older
      women requires careful clinical evaluation with possible laboratory assessment
      using urinalysis and urine culture. Asymptomatic bacteriuria should be
      differentiated from symptomatic UTI. Asymptomatic bacteriuria in older women
      should not be treated.

PMID- 24570252
TI  - Next-day surgical complications after nighttime procedures--reply.

PMID- 24570253
TI  - beta-Blocker therapy for patients with hypertension.

PMID- 24570254
TI  - beta-Blocker therapy for patients with hypertension--reply.

PMID- 24570255
TI  - Patient-physician shared decision making.

PMID- 24570256
TI  - Patient-physician shared decision making--reply.

PMID- 24570258
TI  - Quantitative heredity.

PMID- 24570259
TI  - JAMA patient page. Urinary tract infections in older women.

PMID- 24570260
TI  - Categorical interoception: perceptual organization of sensations from inside.
AB  - Adequate perception of bodily sensations is essential to protect health. However,
      misinterpretation of signals from within the body is common and can be fatal, for
      example, in asthma or cardiovascular disease. We suggest that placing
      interoceptive stimuli into interoceptive categories (e.g., the category of
      symptoms vs. the category of benign sensations) leads to perceptual
      generalization effects that may underlie misinterpretation. In two studies, we
      presented stimuli inducing respiratory effort (respiratory loads) either
      organized into categories or located on a continuous dimension. We found
      pervasive effects of categorization on magnitude estimations, affective stimulus
      evaluations, stimulus recognition, and breathing behavior. These findings
      indicate the need for broadening perspectives on interoception to include basal
      processes of stimulus organization, in order for interoceptive bias to be
      understood. The results are relevant to a wide range of interoception-related
      phenomena, from emotion to symptom perception. 

PMID- 24570262
TI  - Fertility can have different effects on single and nonsingle women: reply to
      Harris and Mickes (2014).

PMID- 24570261
TI  - Inferring character from faces: a developmental study.
AB  - Human adults attribute character traits to faces readily and with high consensus.
      In two experiments investigating the development of face-to-trait inference,
      adults and children ages 3 through 10 attributed trustworthiness, dominance, and
      competence to pairs of faces. In Experiment 1, the attributions of 3- to 4-year
      olds converged with those of adults, and 5- to 6-year-olds' attributions were at
      adult levels of consistency. Children ages 3 and above consistently attributed
      the basic mean/nice evaluation not only to faces varying in trustworthiness
      (Experiment 1) but also to faces varying in dominance and competence (Experiment
      2). This research suggests that the predisposition to judge others using scant
      facial information appears in adultlike forms early in childhood and does not
      require prolonged social experience. 

PMID- 24570263
TI  - Women can keep the vote: no evidence that hormonal changes during the menstrual
      cycle impact political and religious beliefs.

PMID- 24570264
TI  - ELCS in ice: cryo-electron microscopy of nuclear envelope-limited chromatin
      sheets.
AB  - Nuclear envelope-limited chromatin sheets (ELCS) form during excessive interphase
      nuclear envelope growth in a variety of cells. ELCS appear as extended sheets
      within the cytoplasm connecting distant nuclear lobes. Cross-section stained
      images of ELCS, viewed by transmission electron microscopy, resemble a sandwich
      of apposed nuclear envelopes separated by ~30 nm, containing a layer of parallel
      chromatin fibers. In this study, the ultrastructure of ELCS was compared by three
      different methods: (1) aldehyde fixation/dehydration/plastic embedding/sectioning
      and staining, (2) high-pressure freezing/freeze substitution into
      plastic/sectioning and staining, and (3) high-pressure freezing/cryo
      sectioning/cryo-electron microscopy. ELCS could be clearly visualized by all
      three methods and, consequently, must exist in vivo and are not fixation
      artifacts. The ~30-nm chromatin fibers could only be observed following aldehyde
      fixation; none were seen in cryo-sections. Electron microscopic tomography
      tangential views of aldehyde-fixed ELCS suggested an ordering of the separate
      chromatin fibers adjacent to the nuclear envelope. Possible mechanisms of this
      chromatin ordering are discussed. 

PMID- 24570265
TI  - How to derive and validate clinical prediction models for use in intensive care
      medicine.
AB  - BACKGROUND: Clinical prediction models are formal combinations of historical,
      physical examination and laboratory or radiographic test data elements designed
      to accurately estimate the probability that a specific illness is present
      (diagnostic model), will respond to a form of treatment (therapeutic model) or
      will have a well-defined outcome (prognostic model) in an individual patient.
      They are derived and validated using empirical data and used to assist physicians
      in their clinical decision-making that requires a quantitative assessment of
      diagnostic, therapeutic or prognostic probabilities at the bedside. PURPOSE: To
      provide intensivists with a comprehensive overview of the empirical development
      and testing phases that a clinical prediction model must satisfy before its
      implementation into clinical practice. RESULTS: The development of a clinical
      prediction model encompasses three consecutive phases, namely derivation,
      (external) validation and impact analysis. The derivation phase consists of
      building a multivariable model, estimating its apparent predictive performance in
      terms of both calibration and discrimination, and assessing the potential for
      statistical over-fitting using internal validation techniques (i.e. split
      sampling, cross-validation or bootstrapping). External validation consists of
      testing the predictive performance of a model by assessing its calibration and
      discrimination in different but plausibly related patients. Impact analysis
      involves comparative research [i.e. (cluster) randomized trials] to determine
      whether clinical use of a prediction model affects physician practices, patient
      outcomes or the cost of healthcare delivery. CONCLUSIONS: This narrative review
      introduces a checklist of 19 items designed to help intensivists develop and
      transparently report valid clinical prediction models.

PMID- 24570266
TI  - Medical research in emergency research in the European Union member states:
      tensions between theory and practice.
AB  - In almost all of the European Union member states, prior consent by a legal
      representative is used as a substitute for informed patient consent for non
      urgent medical research. Deferred (patient and/or proxy) consent is accepted as a
      substitute in acute emergency research in approximately half of the member
      states. In 12 European Union member states emergency research is not mentioned in
      national law. Medical research in the European Union is covered by the Clinical
      Trial Directive 2001/20/EC. A proposal for a regulation by the European
      Commission is currently being examined by the European Parliament and the Council
      and will replace Directive 2001/20/EC. Deferred patient and/or proxy consent is
      allowed in the proposed regulation, but does not fit completely in the practice
      of emergency research. For example, deferred consent is only possible when legal
      representatives are not available. This criterion will delay inclusion of
      patients in acute life-threatening conditions in short time frames. As the
      regulation shall be binding in its entirety in all member states, emergency
      research in acute situations is still not possible as it should be.

PMID- 24570267
TI  - Cardiopulmonary resuscitation among mechanically ventilated patients.
AB  - PURPOSE: To evaluate the outcomes, including long-term survival, after
      cardiopulmonary resuscitation (CPR) in mechanically ventilated patients. METHODS:
      We analyzed Medicare data from 1994 to 2005 to identify beneficiaries who
      underwent in-hospital CPR. We then identified a subgroup receiving CPR one or
      more days after mechanical ventilation was initiated [defined by ICD-9 procedure
      code for intubation (96.04) or mechanical ventilation (96.7x) one or more days
      prior to procedure code for CPR (99.60 or 99.63)]. RESULTS: We identified 471,962
      patients who received in-hospital CPR with an overall survival to hospital
      discharge of 18.4 % [95 % confidence interval (CI) 18.3-18.5 %]. Of those, 42,163
      received CPR one or more days after mechanical ventilation initiation. Survival
      to hospital discharge after CPR in ventilated patients was 10.1 % (95 % CI 9.8
      10.4 %), compared to 19.2 % (95 % CI 19.1-19.3 %) in non-ventilated patients (p <
      0.001). Among this group, older age, race other than white, higher burden of
      chronic illness, and admission from a nursing facility were associated with
      decreased survival in multivariable analyses. Among all CPR recipients, those who
      were ventilated had 52 % lower odds of survival (OR 0.48, 95 % CI 0.46-0.49, p <
      0.001). Median long-term survival in ventilated patients receiving CPR who
      survived to hospital discharge was 6.0 months (95 % CI 5.3-6.8 months), compared
      to 19.0 months (95 % CI 18.6-19.5 months) among the non-ventilated survivors (p <
      0.001 by logrank test). Of all patients receiving CPR while ventilated, only 4.1
      % were alive at 1 year. CONCLUSIONS: Survival after in-hospital CPR is decreased
      among ventilated patients compared to those who are not ventilated. This
      information is important for clinicians, patients, and family members when
      discussing CPR in critically ill patients.

PMID- 24570269
TI  - [Smoking cessation in patients with COPD].
AB  - Chronic obstructive pulmonary disease (COPD) is a leading cause of death
      worldwide. Cigarette smoking is the main cause of COPD. Quitting smoking is thus
      the most effective treatment strategy and central in COPD prevention. A number of
      guidelines on prevention, diagnosis, therapy and rehabilitation of COPD have been
      published. To help implementing and standardizing smoking cessation in COPD a
      guideline was published 2008 in Germany focusing on this complex issue. The
      present guideline is an update of the 2008 guideline and has a high grade of
      evidence (S3 according to the AWMF; Arbeitsgemeinschaft wissenschaftlicher
      medizinischer Fachgesellschaften). The guideline gives comprehensive and
      practical information on how to integrate smoking cessation as an central part of
      COPD therapy. 

PMID- 24570268
TI  - Nuclear localization of Kaiso promotes the poorly differentiated phenotype and
      EMT in infiltrating ductal carcinomas.
AB  - The expression and biological consequences of Kaiso, a novel bi-modal
      transcription factor, in infiltrating ductal carcinomas (IDCs) have not been
      widely investigated. In the present study, we determined Kaiso expression and
      subcellular localization in 146 normal tissues, 376 IDCs, and 85 lymph node
      metastases. In IDCs, there was higher Kaiso expression in both the cytoplasmic
      and nuclear compartments, which correlated with age <48 (cytoplasmic p < 0.0093;
      nuclear p < 0.0001) and moderate differentiation (cytoplasmic p < 0.0042; nuclear
      p < 0.0001), as determined by Chi square analysis. However, only nuclear Kaiso
      correlated with poor prognostic factors, i.e., race (African Americans) (p <
      0.0001), poor differentiation (p < 0.0001), and metastases (p < 0.0001). Nuclear
      Kaiso was also associated with worse overall survival (p < 0.0019), with African
      American patients displaying worse survival rates relative to Caucasian patients
      (p < 0.029). MCF-7 (non-metastatic), MDA-MB-468 (few metastases), and MDA-MB-231
      (highly metastatic) breast cancer cells demonstrated increasing Kaiso levels,
      with more nuclear localization in the highly metastatic cell line. Over
      expression of Kaiso in MCF-7 cells increased cell migration and invasion, but
      treatment of MDA-MB-468 and MDA-MB-231 cells with si-Kaiso decreased cell
      migration and invasion and induced expression of E-cadherin RNA and protein. E
      cadherin re-expression was associated with a reversal of mesenchymal associated
      cadherins, N-cadherin and cadherin 11, as well as decreased vitamin expression.
      Further, Kaiso directly bound to methylated sequences in the E-cadherin promoter,
      an effect prevented by 5-aza-2-deoxycytidine. Immunofluorescence co-staining of
      poorly differentiated IDCs demonstrated that nuclear Kaiso is associated with a
      loss of E-cadherin expression. These findings support a role for Kaiso in
      promoting aggressive breast tumors.

PMID- 24570270
TI  - Development of new criteria for cortical bone histomorphometry in femoral neck:
      intra- and inter-observer reproducibility.
AB  - Histomorphometry is commonly applied to study bone remodeling. Histological
      definitions of cortical bone boundaries have not been consistent. In this study,
      new criteria for specific definition of the transitional zone between the
      cortical and cancellous bone in the femoral neck were developed. The intra- and
      inter-observer reproducibility of this method was determined by quantitative
      histomorphometry and areal overlapping analysis. The undecalcified histological
      sections of femoral neck specimens (n = 6; from men aged 17-59 years) were
      processed and scanned to acquire histological images of complete bone sections.
      Specific criteria were applied to define histological boundaries. "Absolute
      cortex area" consisted of pure cortical bone tissue only, and was defined mainly
      based on the size of composite canals and their distance to an additional "guide"
      boundary (so-called "preliminary cortex boundary," the clear demarcation line of
      density between compact cortex and sparse trabeculae). Endocortical bone area was
      defined by recognizing characteristic endocortical structures adjacent to the
      preliminary cortical boundary. The present results suggested moderate to high
      reproducibility for low-magnification parameters (e.g., cortical bone area). The
      coefficient of variation (CV %) ranged from 0.02 to 5.61 in the intra-observer
      study and from 0.09 to 16.41 in the inter-observer study. However, the intra
      observer reproducibility of some high-magnification parameters (e.g., osteoid
      perimeter/endocortical perimeter) was lower (CV %, 0.33-87.9). The overlapping of
      three histological areas in repeated analyses revealed highest intra- and inter
      observer reproducibility for the absolute cortex area. This study provides
      specific criteria for the definition of histological boundaries for femoral neck
      bone specimens, which may aid more precise cortical bone histomorphometry. 

PMID- 24570271
TI  - The association between genetic variants of RUNX2, ADIPOQ and vertebral fracture
      in Korean postmenopausal women.
AB  - Contrary to the traditional belief that obesity acts as a protective factor for
      bone, recent epidemiologic studies have shown that body fat might be a risk
      factor for osteoporosis and bone fracture. Accordingly, we evaluated the
      association between the phenotypes of osteoporosis or vertebral fracture and
      variants of obesity-related genes, peroxisome proliferator-activated receptor
      gamma (PPARG), runt-related transcription factor 2 (RUNX2), leptin receptor
      (LEPR), and adiponectin (ADIPOQ). In total, 907 postmenopausal healthy women,
      aged 60-79 years, were included in this study. BMD and biomarkers of bone health
      and adiposity were measured. We genotyped for four single nucleotide
      polymorphisms (SNPs) from four genes (PPARG, RUNX2, LEPR, ADIPOQ). A general
      linear model for continuous dependent variables and a logistic regression model
      for categorical dependent variables were used to analyze the statistical
      differences among genotype groups. Compared with the TT subjects at rs7771980 in
      RUNX2, C-carrier (TC + CC) subjects had a lower vertebral fracture risk after
      adjusting for age, smoking, alcohol, total calorie intake, total energy
      expenditure, total calcium intake, total fat intake, weight, body fat. Odds ratio
      (OR) and 95% interval (CI) for the vertebral fracture risk was 0.55 (95% CI 0.32
      0.94). After adjusting for multiple variables, the prevalence of vertebral
      fracture was highest in GG subjects at rs1501299 in ADIPOQ (p = 0.0473). A high
      calcium intake (>1000 mg/day) contributed to a high bone mineral density (BMD) in
      GT + TT subjects at rs1501299 in ADIPOQ (p for interaction = 0.0295). Even if the
      mechanisms between obesity-related genes and bone health are not fully
      established, the results of our study revealed the association of certain SNPs
      from obesity-related genes with BMD or vertebral fracture risk in postmenopausal
      Korean women.

PMID- 24570272
TI  - Anthocyanins, phenolic acids and antioxidant properties of Jucara fruits (Euterpe
      edulis M.) along the on-tree ripening process.
AB  - Jucara (Euterpe edulis M.) fruits are an interesting source of phenolic
      compounds, mainly anthocyanins, making them valuable to the food and
      pharmaceutical industries. Jucara fruits were harvested along the on-tree
      ripening process between March and June as practiced in Parana state, Brazil and
      examined for their total anthocyanin content (TAC), total phenolic content (TPC),
      total phenolic acid (TPA) and total antioxidant capacity (TAA). Overall, TAC
      increased (91.52-236.19 mg cyanidin-3-glucoside equivalent/100 g dm) whereas TPC
      (81.69-49.09 mg GAE/g dm) and TPA (44.27-30.95 mg/100 g dm) decreased during
      ripening of jucara fruits. Use of tandem mass spectrometry allowed the
      identification of cyanidin-3,5-diglucoside, peonidin-3-glucoside and peonidin-3
      rutinoside for the first time in jucara fruits. The analysis of the phenolic
      acids by HPLC-MS/MS indicated the presence of gallic, protocatechuic, p
      hydroxybenzoic, vanillic, chlorogenic, caffeic, syringic, p-coumaric, sinapinic
      and ferulic acids. The high antioxidant capacity using DPPH radical scavenging
      capacity (655.89-745.32 MUmol TE/g dm) and ORAC assays (1088.10-2071.55 MUmol
      TE/g dm) showed that jucara fruits have potential as a source of novel natural
      antioxidants for disease prevention and health promotion, and also as natural
      food additives for developing new functional food products. 

PMID- 24570273
TI  - Effect of a tart cherry juice supplement on arterial stiffness and inflammation
      in healthy adults: a randomised controlled trial.
AB  - Tart cherries are a particularly rich source of anthocyanins. Evidence indicates
      that dietary intake of anthocyanins is inversely associated with arterial
      stiffness. We conducted an open-label randomised placebo controlled study to
      determine whether a tart cherry juice concentrate (Cherry Active) reduced
      arterial stiffness, inflammation and risk markers for cardiovascular disease in
      47 healthy adults (30-50 years). Participants consumed 30 ml of cherry
      concentrate diluted to a volume of 250 ml with water or the same volume of an
      energy matched control drink daily for six weeks. Measurements were taken at
      baseline and at the end of the intervention. There was no effect of the
      intervention on arterial stiffness (P = 0.218), c-reactive protein (P = 0.220),
      systolic blood pressure (P = 0.163), diastolic blood pressure (P = 0.121), total
      cholesterol (P = 0.342) and high density lipoprotein cholesterol (P = 0.127). At
      the end of the intervention, plasma antioxidant capacity (measured as the ferric
      reducing ability of plasma (FRAP)) was significantly higher in the intervention
      group than the control group (P = 0.012). We conclude that a tart cherry juice
      concentrate rich in anthocyanins has no effect on arterial stiffness, c-reactive
      protein and risk markers for cardiovascular disease, but evokes a minor increase
      in antioxidant status in healthy adults.

PMID- 24570276
TI  - Usefulness of contrast enhanced FLAIR imaging for predicting the severity of
      meningitis.
AB  - The aim of this study was to evaluate whether contrast enhanced fluid attenuated
      inversion recovery (CE-FLAIR) imaging can be used to predict the severity of
      meningitis based on leptomeningeal enhancement (LE) score and cerebrospinal fluid
      signal intensity (CSF-SI) on CE-FLAIR. We retrospectively analyzed data collected
      from 43 consecutive patients admitted to our hospital due to meningitis. Clinical
      factors including initial Glasgow Coma Scale (GCS) score, CSF glucose ratio, log
      CSF protein, log CSF WBC, and prognosis were evaluated. The LE score was semi
      quantitatively scored, and we evaluated CSF-SI ratio at the interpeduncular or
      quadrigerminal cisterns on CE-FLAIR. We evaluated the differences in clinical
      variables, LE scores and CSF-SI ratios between the recovery and the complication
      group. We assessed the correlation between clinical variables, LE scores and CSF
      SI ratios. The values of log CSF protein, CSF-SI ratio, and LE score were
      significantly higher in the complication group (p value <0.05). GCS score and CSF
      glucose ratio were significantly lower in the complication group (p value <0.01).
      The LE scores had significant negative correlation with GCS scores and CSF
      glucose ratios (p value <0.001). The LE score was significantly positively
      correlated with the value of log CSF protein and CSF-SI ratio (p value <0.01).
      The CSF-SI ratio was negatively correlated with GCS score and CSF glucose ratio
      (p value <0.01). The CSF-SI ratio was positively correlated with the value of log
      CSF protein (p value <0.05). Our results suggest that LE score and CSF-SI ratio
      are well correlated with clinical prognostic factors. We may predict the clinical
      severity of meningitis by using LE scores and CSF-SI ration on CE-FLAIR imaging.

PMID- 24570277
TI  - A case of steroid-responsive MADSAM with late appearance of a partial conduction
      block in the forearm.

PMID- 24570275
TI  - Feeling happy enhances early spatial encoding of peripheral information
      automatically: electrophysiological time-course and neural sources.
AB  - Previous research has shown that positive mood may broaden attention, although it
      remains unclear whether this effect has a perceptual or a postperceptual locus.
      In this study, we addressed this question using high-density event-related
      potential methods. We randomly assigned participants to a positive or a neutral
      mood condition. Then they performed a demanding oddball task at fixation (primary
      task ensuring fixation) and a localization task of peripheral stimuli shown at
      three positions in the upper visual field (secondary task) concurrently. While
      positive mood did not influence behavioral performance for the primary task, it
      did facilitate stimulus localization on the secondary task. At the
      electrophysiological level, we found that the amplitude of the C1 component
      (reflecting an early retinotopic encoding of the stimulus in V1) was enhanced in
      the positive, as compared with the neutral, mood group. Importantly, this effect
      appeared to be largely automatic, because it occurred regardless of the task
      relevance of the peripheral stimulus and prior to top-down gain control effects
      seen at the level of the subsequent P1 component. This early effect was also
      observed irrespective of a change of the target-related P300 component (primary
      task) by positive mood. These results suggest that positive mood can
      automatically boost the spatial encoding of peripheral stimuli early on following
      stimulus onset. This effect can eventually underlie the broadening of spatial
      attention, which has been associated with this specific mood state. 

PMID- 24570278
TI  - Predictive mechanisms improve the vestibulo-ocular reflex in patients with
      bilateral vestibular failure.

PMID- 24570280
TI  - Diagnostic profiles of patients with late-onset Creutzfeldt-Jakob disease differ
      from those of younger Creutzfeldt-Jakob patients: a historical cohort study using
      data from the German National Reference Center.
AB  - In contrast to other neurodegenerative diseases, sporadic Creutzfeldt-Jakob
      disease (sCJD) is rarely diagnosed in patients older than 75 years. Data
      describing the characteristics of sCJD in the very old are rare and inconclusive.
      Therefore, a historical cohort study was designed to evaluate clinical,
      cerebrospinal fluid (CSF), electroencephalography (EEG), and magnetic resonance
      imaging (MRI) features of this group. Patients older than 75 years identified via
      the German surveillance program from 2001 to 2012 (n = 73) were compared to a
      random subsample of sCJD patients younger than 75 (n = 73) from the same time
      period using an historical cohort design. Older patients showed a faster disease
      progression represented by an earlier point of diagnosis and a shorter survival
      time (p < 0.001). In the early stages of disease, older patients presented
      slightly more often with dementia (p = 0.127) or dysarthria (p = 0.238), whereas
      disorders of the extrapyramidal (p = 0.056) and visual system (p = 0.015) were
      more common in the younger group. Atypical MRI profiles such as MRI lesions
      restricted to one hemisphere (p < 0.001) or cortical lesions only (p = 0.258)
      were found more frequently in patients older than 75 years, whereas typical
      cortical and basal ganglia hyperintensities were more common in the younger group
      (p = 0.001). We demonstrated for the first time that patients with late-onset
      sCJD differ from younger sCJD patients with respect to MRI profiles and initial
      clinical presentation, but not among CSF markers. Misclassification of
      Creutzfeldt-Jakob disease cases in patients older than 75 years seems likely due
      to atypical clinical and radiological presentation. This might contribute to
      lower sCJD incidence rates in this age group.

PMID- 24570279
TI  - Central cholinergic dysfunction in the adult form of Niemann Pick disease type C:
      a further link with Alzheimer's disease?
AB  - Adult patients with Niemann-Pick disease type C (NPC) usually develop cognitive
      impairment progressing to dementia, whose pathophysiology remains still unclear.
      Noteworthy parallels exist in cognitive impairment and cellular pathology of NPC
      and Alzheimer's disease (AD). In particular, alterations of cholinergic system,
      which represent one of the pathological hallmarks and contribute to cognitive
      deterioration in AD, have recently been demonstrated in a human brain autopsy and
      in an experimental model of NPC. This finding raised the issue that central
      cholinergic circuits dysfunction may contribute to pathophysiology of cognitive
      impairment in NPC as well, and prompted us to evaluate the cholinergic functional
      involvement in NPC patients by applying a neurophysiologic technique, named short
      latency afferent inhibition (SAI). We describe clinical, biochemical, molecular
      and neuropsychological features, and SAI findings in three patients affected by
      NPC. Diagnosis of NPC was assessed by molecular analysis of the NPC1 gene in all
      patients. In two of them, biochemical analysis of intracellular accumulation of
      unesterified cholesterol was also performed. The main clinical features were
      cerebellar ataxia, vertical supranuclear gaze palsy and a variable degree of
      cognitive impairment ranging from only memory impairment to severe dementia.
      Electrophysiological evaluation revealed a reduced SAI in all three patients. Our
      SAI findings provide evidence of cholinergic dysfunction in patients with the
      adult form of NPC, supporting that cholinergic alterations may play a role in
      cognitive impairment in NPC, and strengthening the similarities between NPC and
      AD.

PMID- 24570281
TI  - Interpreting therapeutic effect in multiple sclerosis via MRI contrast enhancing
      lesions: now you see them, now you don't.
AB  - Gadolinium (Gd) enhancement of multiple sclerosis (MS) lesions on MRI scans is a
      commonly used outcome measure in therapeutic trials. However, enhancement depends
      on MRI acquisition parameters that might significantly alter detectability. We
      investigated how the difference in blood-brain barrier (BBB) permeability
      threshold between MRI protocols affects lesion detection and apparent enhancement
      time using dynamic-contrast-enhanced (DCE) MRI. We examined fourty-four relapsing
      remitting MS patients with two MRI protocols: 'standard sensitivity' (SS) (1.5 T,
      single-dose Gd) and 'high sensitivity' (HS) (3 T, triple-dose Gd, delayed
      acquisition). Eleven patients had at least one enhancing lesion and completed the
      1-month follow-up. We acquired DCE-MRI during the HS protocol and calculated BBB
      permeability. Sixty-five lesions were enhanced with the SS vs. 135 with the HS
      protocol. The detection threshold of the HS was significantly lower than that of
      the SS protocol (K trans = 2.64 vs. 4.00E-3 min(-1), p < 0.01). Most lesions (74
      %) were in the recovery phase; none were in the onset phase and 26 % were at the
      peak of enhancement. The estimated duration of detectability with the HS protocol
      was significantly longer than for the SS protocol (6-12 weeks vs. 3 weeks). Our
      observations on the protocol-dependent threshold for detection and time-course
      help explain discrepancies in the observed effects of anti-inflammatory therapies
      on MS lesions.

PMID- 24570282
TI  - Successful thrombolysis of stroke with intravenous alteplase in the third
      trimester of pregnancy.

PMID- 24570284
TI  - Canal conversion after repositioning procedures: comparison of Semont and Epley
      maneuver.
AB  - Although the efficacy of Semont (SM) and Epley maneuvers (EM) for treatment of
      posterior canal benign paroxysmal positional vertigo (BPPV) is well established,
      data comparing SM and EM regarding maneuver-induced canal switch are lacking. We
      prospectively investigated 102 posterior canal BPPV patients after application of
      the Semont or the Epley maneuver and looked for the appearance of ipsilateral
      horizontal canal BPPV symptoms. Although treatment success was similar for SM and
      EM (67 and 76 %, respectively), there was a significant difference in posterior
      to-horizontal canal switch rates. In particular, 4 of 51 patients (7.8 %) of the
      EM group converted to the geotropic type of horizontal canal BPPV, whereas none
      of the 51 SM patients exhibited a canal switch. All four patients were cleared
      with a single barbecue maneuver. Our data suggest a small but significant
      difference in canal switch rate between EM and SM, which could be partly
      explained by the higher number of maneuver steps during which the head is in the
      dependent position throughout the EM.

PMID- 24570283
TI  - Childhood onset tubular aggregate myopathy associated with de novo STIM1
      mutations.
AB  - We investigated three unrelated patients with tubular-aggregate myopathy and
      slowly progressive muscle weakness manifesting in the first years of life. All
      patients showed type 1 muscle fiber predominance and hypotrophy of type 2 fibers.
      Tubular aggregates were abundant. In all three patients mutations were identified
      in the gene STIM1, and the mutations were found to be de novo in all patients. In
      one of the patients the mutation was identified by exome sequencing. Two patients
      harbored the previously described mutation c.326A>G p.(His109Arg), while the
      third patient had a novel mutation c.343A>T p.(Ile115Phe). Taking our series
      together with previously published cases, the c.326A>G p.(His109Arg) seems to be
      a hotspot mutation that is characteristically related to early onset muscle
      weakness.

PMID- 24570285
TI  - The Role of Cyclooxygenase-1 and -2 in Sevoflurane-Induced Postconditioning
      Against Myocardial Infarction.
AB  - Cyclooxygenase (COX)-2 mediates ischemic pre- and postconditioning as well as
      anesthetic-induced preconditioning. However, the role of COX-1 and -2 in
      anesthetic-induced postconditioning has not been investigated. We evaluated the
      role of COX-1 and -2 in sevoflurane-induced postconditioning in vivo.
      Pentobarbital-anaesthetized male C57BL/6 mice were subjected to 45 minutes of
      coronary artery occlusion and 3 hours of reperfusion. Animals received either no
      intervention, the vehicle dimethyl sulfoxide (DMSO, 10 uL/g intraperitoneally),
      acetylsalicylic acid (ASA, 5 ug/g intraperitoneally), the selective COX-1
      inhibitor SC-560 (10 ug/g intraperitoneally), or the selective COX-2 inhibitor NS
      398 (5 ug/g intraperitoneally). 1.0 MAC (minimum alveolar concentration)
      sevoflurane was administered for 18 minutes during early reperfusion either alone
      or in combination with ASA, SC-560, and NS-398. Infarct size was determined with
      triphenyltetrazolium chloride. Statistical analysis was performed using 1-way and
      2-way analyses of variance with post hoc Duncan testing. The infarct size in the
      control group was 44% +/- 9%. DMSO (42% +/- 7%), ASA (36% +/- 6%), and NS-398
      (44% +/- 18%) had no effect on infarct size. Sevoflurane (17% +/- 4%; P < .05)
      and SC-560 (26% +/- 10%; P < .05) significantly reduced the infarct size compared
      with control condition. Sevoflurane-induced postconditioning was not abolished by
      ASA (16% +/- 5%) and SC-560 (22% +/- 4%). NS-398 abolished sevoflurane-induced
      postconditioning (33% +/- 14%). It was concluded that sevoflurane induces
      postconditioning in mice. Inhibition of COX-1 elicits a myocardial infarct size
      reduction and does not abolish sevoflurane-induced postconditioning. Blockade of
      COX-2 abolishes sevoflurane-induced postconditioning. These results indicate that
      sevoflurane-induced postconditioning is mediated by COX-2. 

PMID- 24570287
TI  - [Mental health promotion in school with school coaches: evaluation of a pilot
      project].
AB  - OBJECTIVE: How did the work of four school coaches in five Saxonian schools
      influence children's and adolescents' psychosocial development? METHODS: At three
      points in time, students at intervention (N = 292) and control schools (N = 300)
      were evaluated concerning their social distance towards mentally ill people and
      their help-seeking behavior in case of crisis. The survey also included teachers
      (N = 323) and parents (N = 370). Data analysis was done descriptively and with
      random effects models. RESULTS: The social distance of the intervention schools
      declined significantly compared to the control schools. Having heard or read
      about mental illnesses, or personally knowing somebody affected by mental
      illness, led to less social distance and more empathy. Information increased the
      confidence to receive help from a professional consultant. Friends and family
      were the main reference groups. The school coaches were accepted as confidential
      persons and helped with school and private issues. CONCLUSION: The school
      coaches' work showed positive influence on all members of the school system.

PMID- 24570288
TI  - [First contact with psychiatric services: what do relatives caring for
      schizophrenia patients need?].
AB  - OBJECTIVE: The purpose of the present study was to investigate the problems and
      needs for interventions among caregivers of patients with schizophrenia who were
      the first time in contact with psychiatric services. METHODS: 93 family
      caregivers of schizophrenia patients during the first contact with services were
      investigated by means of the the "Carer's Needs Assessment for Schizophrenia"
      (CNA-S). RESULTS: The most frequent problems of caregivers of first contact
      patients with schizophrenia were insufficient information on mental illness and
      concerns about the patient's future. Individual psychoeducation was needed
      significantly more often among caregivers of first contact patients than among
      those having been previously in contact with psychiatric services. CONCLUSION:
      Those being the first time in contact with psychiatric services need some
      specific interventions significantly more often than later.

PMID- 24570289
TI  - [German version of the Marce-Clinical-Checklist as a basic documentation for
      inpatient mother-and-baby units: evaluation of the MKE Herten data].
AB  - OBJECTIVE: Evaluation of the psychiatric mother-and-child treatment, the goal
      being to find predictive factors for a positive treatment result. METHODS:
      Statistical assessment of 166 treatment dyads by using the Marce-Clinical
      Checklist (11/2006-12/2011). RESULTS: About 90% of (women) patients show a
      positive success of the treatment.Disease severity at admission, social status,
      education or the illness of the partner are significant influential factors.
      CONCLUSION: In the field of perinatal psychiatry mother-and-child treatment is
      effective, social risk factors have a significant influence on the success of the
      treatment.

PMID- 24570290
TI  - Efinaconazole: a new topical treatment for onychomycosis.
AB  - Efinaconazole is an emerging antifungal therapy for the topical treatment of
      onychomycosis. Efinaconazole is an inhibitor of sterol 14alpha-demethylase and is
      more effective in vitro than terbinafine, itraconazole, ciclopirox and amorolfine
      against dermatophytes, yeasts and non-dermatophyte molds. Phase II studies
      indicate that efinaconazole 10% nail solution is more effective than either the
      5% strength or 10% solution with semi-occlusion. In duplicate Phase III clinical
      trials, complete cure rates of 17.8% and 15.2% were demonstrated. The mean
      mycological cure rate for efinaconazole is similar to the oral antifungal
      itraconazole and exceeds the efficacy of topical ciclopirox. Efinaconazole showed
      minimal localized adverse events, which ceased upon stopping treatment. Overall,
      efinaconazole 10% nail solution is an effective topical monotherapy for distal
      and lateral subungual onychomycosis (<65% nail involvement, excluding the matrix)
      that shows further potential use as an adjunct to oral and device-based
      therapies. 

PMID- 24570291
TI  - Steroid-sparing properties of emollients in dermatology.
AB  - Topical corticosteroids (TCS) and topical calcineurin inhibitors (TCIs) are very
      effective treatments in inflammatory dermatoses, but carry risks with long-term
      use. TCS are associated with cutaneous atrophy and tachyphylaxis and TCIs can be
      irritating and contain a black box warning of an increased risk of cancers
      including lymphoma and non-melanomatous skin cancers. Nevertheless, they are
      appropriate treatments for inflammatory conditions such as psoriasis and atopic
      dermatitis (AD) and should be used more often with disease flares and less as
      maintenance therapy. Given the associated risks of long-term continuous use with
      these pharmacologic agents, alternatives are needed with similar anti
      inflammatory and barrier repair properties that can be used indefinitely without
      risk. Some over-the-counter (OTC) ingredients such as colloidal oatmeal and
      petrolatum, as well as anti-inflammatory prescription moisturizers (medical
      device creams), have demonstrated efficacy with little complications in skin
      barrier repair and symptom relief in steroid-responsive conditions. With
      regimented application, these non-drug options are safe and effective and can
      limit the longterm continuous use of TCS or TCIs. 

PMID- 24570292
TI  - Occupational radiation monitoring at a large medical center in Japan.
AB  - Occupational radiation dose monitoring is a method of ensuring that radiation
      levels are within the regulatory limits. Our objective in this study was to
      evaluate the radiation doses experienced by personnel at a radiology facility
      between 2001 and 2010. Overall, 2418 annual dose records for workers who were
      categorized into four occupational groups were analyzed. The groups included: (1)
      radiologists, (2) radiologic technologists, (3) nurses, and (4) other workers,
      who belong to other hospital departments, but who participate partially in some
      radiologic procedures. The dose distribution was found to be skewed, with 76 % of
      personnel having received no measurable doses and almost 2 % having received
      doses of more than 2 mSv. The weighted-average annual doses ranged from 0.13 to
      0.57, 0.9 to 2.12, 0.01 to 0.19, and 0.01 to 0.09 mSv for the radiologists,
      radiologic technologists, nurses, and the other workers, respectively. The
      radiologic technologists received the highest radiation exposure among the four
      groups. It was found that the average annual doses were decreasing over time for
      the radiologists, radiologic technologists, and others, whereas they were
      increasing for the nurses. Nurses play an important role in assisting
      radiologists and patients during various radiologic procedures, which might have
      increased their average annual dose. During the 10-year period of this study,
      there was no incidence of a dose exceeding the annual dose limit of 20 mSv.
      Furthermore, there was no detectable neutron exposure.

PMID- 24570293
TI  - Microalga Euglena as a bioindicator for testing genotoxic potentials of organic
      pollutants in Taihu Lake, China.
AB  - The microalga Euglena was selected as a bioindicator for determining genotoxicity
      potencies of organic pollutants in Meiliang Bay of Taihu Lake, Jiangsu, China
      among seasons in 2008. Several methods, including the comet assay to determine
      breaks in DNA and quantification of antioxidant enzymes were applied to
      characterize genotoxic effects of organic extracts of water from Taihu Lake on
      the flagellated, microalga Euglena gracilis. Contents of photosynthetic pigments,
      including Chl a, Chl b and carotenoid pigments were inversely proportion to
      concentrations of organic extracts to which E. gracilis was exposed. Organic
      extracts of Taihu Lake water also affected activities of superoxide dismutase
      (SOD) and peroxidase (POD) of E. gracilis. There were no statistically
      significant differences in SOD activities among seasons except in June but
      significant differences in POD activities were observed among all seasons. The
      metrics of DNA fragmentation in the alkaline unwinding assay (Comet assay), olive
      tail moment (OTM) and tail moment (TM), used as measurement endpoints during the
      genotoxicity assay were both greater when E. gracilis was exposed to organic of
      water collected from Taihu Lake among four seasons. It is indicated that the
      comet assay was useful for determining effects of constituents of organic
      extracts of water on E. gracilis and this assay was effective as an early warning
      to organic pollutants. 

PMID- 24570294
TI  - Causal relationship between the AHSG gene and BMD through fetuin-A and BMI:
      multiple mediation analysis.
AB  - Using mediation analysis, a causal relationship between the AHSG gene and bone
      mineral density (BMD) through fetuin-A and body mass index (BMI) mediators was
      suggested. INTRODUCTION: Fetuin-A, a multifunctional protein of hepatic origin,
      is associated with bone mineral density. It is unclear if this association is
      causal. This study aimed at clarification of this issue. METHODS: A cross
      sectional study was conducted among 1,741 healthy workers from the Electricity
      Generating Authority of Thailand (EGAT) cohort. The alpha-2-Heremans-Schmid
      glycoprotein (AHSG) rs2248690 gene was genotyped. Three mediation models were
      constructed using seemingly unrelated regression analysis. First, the ln[fetuin
      A] group was regressed on the AHSG gene. Second, the BMI group was regressed on
      the AHSG gene and the ln[fetuin-A] group. Finally, the BMD model was constructed
      by fitting BMD on two mediators (ln[fetuin-A] and BMI) and the independent AHSG
      variable. All three analyses were adjusted for confounders. RESULTS: The
      prevalence of the minor T allele for the AHSG locus was 15.2%. The AHSG locus was
      highly related to serum fetuin-A levels (P < 0.001). Multiple mediation analyses
      showed that AHSG was significantly associated with BMD through the ln[fetuin-A]
      and BMI pathway, with beta coefficients of 0.0060 (95% CI 0.0038, 0.0083) and
      0.0030 (95% CI 0.0020, 0.0045) at the total hip and lumbar spine, respectively.
      About 27.3 and 26.0% of total genetic effects on hip and spine BMD, respectively,
      were explained by the mediation effects of fetuin-A and BMI. CONCLUSIONS: Our
      study suggested evidence of a causal relationship between the AHSG gene and BMD
      through fetuin-A and BMI mediators.

PMID- 24570295
TI  - Longitudinal changes and seasonal variations in serum 25-hydroxyvitamin D levels
      in different age groups: results of the Longitudinal Aging Study Amsterdam.
AB  - Vitamin D levels remained fairly stable during ageing with increasing levels in
      persons aged 55-65 years old and decreasing levels in persons aged 65-88 years
      old. The seasonal variation was larger than the longitudinal change. Our findings
      implicate that vitamin D supplementation becomes more important in older age
      groups and during wintertime. INTRODUCTION: Longitudinal changes in serum 25
      hydroxyvitamin D (25-OHD) levels during aging have not been studied extensively.
      Two studies showed increasing serum 25-OHD levels. One of these studies suggested
      that there might be decreasing levels in persons aged 65 years and older. The
      objectives of the current study are the following: (1) to examine longitudinal
      changes in serum 25-OHD levels in different age groups and (2) to describe the
      seasonal variation in different age groups. METHODS: Data of the Longitudinal
      Aging Study Amsterdam (LASA), an ongoing cohort study, were used. Two different
      cohorts were included: (1) younger cohort: aged 55-65 years old at baseline, n =
      738, follow-up of 6 years and (2) older cohort: aged 65-88 years old at baseline,
      n = 1,320, follow-up of 13 years. RESULTS: At baseline, average levels were 56.5
      nmol/L in the younger cohort and 51.1 nmol/L in the older cohort. In the younger
      cohort, a longitudinal increase in the mean serum 25-OHD levels of 4 nmol/L in 6
      years was observed; in the older cohort, a longitudinal decrease in the mean
      serum 25-OHD levels of 4 nmol/L in 13 years was observed. The seasonal variation
      was +/-12 nmol/L in the younger cohort and +/-7 nmol/L in the older cohort.
      CONCLUSIONS: Long-term serum 25-OHD levels remained fairly stable during aging
      with slightly increasing levels in persons aged 55-65 years old and slightly
      decreasing levels in persons aged 65-88 years old. On average, the seasonal
      variation was larger than the longitudinal change. Our findings implicate that
      vitamin D supplementation becomes more important in older age groups and during
      wintertime.

PMID- 24570296
TI  - Theoretical consideration of the effect of drug holidays on BMD and tissue age.
AB  - It has been suggested that some patients undergoing prolonged treatment for
      osteoporosis with anti-resorptive agents may benefit from discontinuing
      treatment. Here we use a computer simulation of bone cell activity to estimate
      changes in bone mineral density (BMD) and tissue age when treatment is
      discontinued. INTRODUCTION: Although anti-resorptive agents are effective at
      reducing fracture risk, questions remain regarding how long patients should
      continue treatment and how long treatment should be discontinued. Suspending
      treatment as part of a drug holiday may reduce the risk of adverse effects, but
      may also lead to reduced BMD. METHODS: We use a computer simulation of the bone
      remodeling process to estimate how BMD and mean tissue age are changed after
      treatment is suspended. Mean tissue age is studied because increased tissue age
      has been associated with impaired bone quality and has been linked to the risk of
      adverse effects. RESULTS: Our simulations suggest that BMD gains from anti
      resorptive therapy can be lost over time, especially with anti-resorptive agents
      that have little residual effects. With regard to mean tissue age, the
      simulations suggest that increases in tissue age from anti-resorptive treatment
      are long lasting; increases in mean tissue age caused by treatment may remain for
      as long as 15 years after treatment is suspended. After stopping treatment,
      reductions in BMD are expected to occur long before mean tissue age returns to
      normal. CONCLUSIONS: Our simulations suggest that, when using a long-lasting anti
      resorptive agent, 1- to 5-year drug holidays may have little effect on BMD in
      most patients but that drug holiday intervals that maintain BMD are unlikely to
      reverse alterations in tissue age caused by treatment. Our analysis echoes recent
      reviews suggesting patient selection and monitoring when anti-resorptive
      treatment is discontinued.

PMID- 24570297
TI  - Proactive pharmaceutical care interventions decrease patients' nonadherence to
      osteoporosis medication.
AB  - Using a protocolled intervention program, pharmacists can decrease nonadherence
      to osteoporosis medication, by continuous monitoring and tailored counseling
      sessions, starting at treatment initiation. In the usual care group, 32.8% of
      patients initiating osteoporosis medication discontinued or were nonadherent,
      compared to 19.0% of patients in the intervention group. PURPOSE: While community
      pharmacies have been shown to offer a promising platform for osteoporosis
      management in patients with osteoporosis, more research is needed to determine
      pharmacists' effects on improving adherence. The aim of this study was to
      determine the effects of a community pharmacists' intervention program on the 1
      year discontinuation and nonadherence rates of patients initiating osteoporosis
      medication. METHODS: This intervention study included 937 patients, recruited
      from 13 Dutch community pharmacies, initiating osteoporosis medication. The
      intervention group (N = 495), received the Medication Monitoring and Optimization
      (MeMO) intervention, comprising of continuous monitoring of patients' adherence
      to their osteoporosis medication and tailored counseling sessions with
      nonadherent patients. Results were compared to an internal (n = 442) reference
      group, receiving usual pharmacy care. Primary study outcomes were therapy
      discontinuation and nonadherence; results were adjusted for potential confounders
      using Cox proportional hazard analysis. Secondary outcome was patients'
      satisfaction. RESULTS: In the usual care group, 32.8% of patients initiating
      osteoporosis medication discontinued or were nonadherent, compared to 19.0% of
      patients in the intervention group (P < 0.001). Ninety-three percent of the
      respondents were satisfied with the pharmacies' services provided. Notably, 31%
      mentioned that the pharmacy was the only place where they received information on
      various aspects of administration and acting of their medication. CONCLUSION:
      Pharmacists can decrease nonadherence and discontinuation with osteoporosis
      medication by providing tailored counseling sessions and continuous monitoring of
      drug use. Pharmaceutical care programs, such as MeMO, contribute to more optimal
      use of osteoporosis medication.

PMID- 24570298
TI  - Cost of managing anemia in end-stage renal disease: the experience of five French
      dialysis centers.
AB  - OBJECTIVE: The aim of this retrospective study was to evaluate the direct cost of
      anemia treatment in hemodialysis patients and to evidence factors predictive of 1
      year cost. METHODS: Retrospective study which included hemodialyzed patients
      during year 2009 in five centers. Patients were evaluable if they had at least
      one hemoglobin (Hb) assay per month and were monitored for at least 4 months.
      Patients were classified in different "annual Hb category" according to their
      monthly mean Hb [Hb categories: Ideal (10 <= Hb <= 12 g/dL); High (Hb > 12 g/dL)
      and Low (Hb < 10 g/dL) if >75% of time in respective category, otherwise
      classified in the Fluctuating category]. RESULTS: We analyzed 636 patients (male,
      59.4%) with a mean age of 67 years who underwent 144 hemodialysis sessions
      (median number per patient) in 2009. The cost of anemia treatment was largely
      driven by erythropoiesis-stimulating agents (ESA) (68% of total cost for Low Hb
      category and approximately 90% for the other Hb categories). Adjusted predictive
      factors for 1-year direct cost of anemia treatment (p < 0.0001) were dialysis
      center (<euro>2,518-<euro>5,617), death (<euro>6,091 vs. <euro>4,911), age
      (<euro>4,911 for <=55 years and <euro>5,378 for 65-75 years), female gender
      (<euro>4,911 vs. <euro>4,398 for male), Low Hb category (<euro>13,005 vs.
      <euro>5,034 for Ideal, <euro>4,911 for Fluctuating and <euro>2,418 for High),
      serum ferritin level (<euro>5,102 for 200-500 MUg/mL and <euro>4,646 for >=500
      MUg/mL) and duration of dialysis (<euro>4,911 if <=2 years and <euro>2,952 if 4-6
      years). LIMITATIONS: Retrospective study, and low number of patients in the Low
      Hb category. CONCLUSIONS: The main factors that were predictive of 1-year cost of
      anemia treatment in hemodialysis patients were centers, patients in the Low Hb
      category, and dialysis duration of less than 2 years.

PMID- 24570274
TI  - Treatment of unicameral bone cyst: systematic review and meta analysis.
AB  - PURPOSE: Different treatment modalities have been utilized to treat unicameral
      bone cyst (UBC), but evidence has not been fully described to support one
      treatment over another and the optimal treatment is controversial. The aim of
      this quantitative systematic review was to assess the effectiveness of different
      UBC treatment modalities. METHODS: We utilized Pubmed to isolate retrospective
      studies on patients with UBC who received any kind of treatment. The included
      studies needed to have a minimum sample size of 15 patients, and have provided
      data on radiographic healing outcome. RESULTS: Sixty-two articles were selected
      for the meta-analysis from a total of 463 articles. The cumulative sample size
      was 3,211 patients with 3,217 UBC, and male to female ratio was 2.2:1. The
      summary or pool estimate of methylprednisolone acetate (MPA) injection resulted
      in a healing rate of (77.4 %) that was comparable to bone marrow injection (77.9
      %). A higher healing rate was observed with MPA injection when inner wall
      disruption was performed. The pool estimate of bone marrow with demineralized
      bone matrix injection was high (98.7 %). UBC healing rate after surgical
      curettage was comparable whether autograft or allograft was utilized (90 %). UBC
      treatment with flexible intramedullary nails without curettage provided almost
      100% healing rate, while continuous decompression with cannulated screws provided
      89 % healing rate. Conservative treatment indicated a healing rate of 64.2, 95 %
      CI (26.7-101.8). CONCLUSIONS: Active treatment for UBC provided variable healing
      rates and the outcomes were favorable relative to conservative treatment. Due to
      the heterogeneity of the studies and reporting bias, the interpretation of these
      findings should be handled with caution.

PMID- 24570299
TI  - Association between roentgenographic findings of the cervical spine and neck
      symptoms in a Japanese community population.
AB  - BACKGROUND: Radiographic findings may provide clues to the underlying cause of
      neck symptoms. However, these associations remain controversial. This study
      investigates the association between roentgenographic findings of the cervical
      spine and neck symptoms in a Japanese community population. METHODS: A total of
      762 volunteers participated in this study. Sagittal radiographs of the cervical
      spine were taken and a questionnaire about the presence of and visual analog
      scale (VAS) for neck pain or stiff shoulder was completed. The sagittal alignment
      of the cervical spine (C2-C7) and the degenerative index were measured from
      lateral aspect radiographs. Three groups based on the sagittal alignment of C2-C7
      were defined: straight-spine, lordotic-spine, and kyphotic-spine. The
      roentgenographic findings were examined in relation to symptoms. RESULTS: The
      prevalence rate of stiff shoulder on the day of examination was significantly
      higher in females than males. Although the VAS for neck pain and stiff shoulder
      on the examination day and for stiff shoulder in the preceding 12 months were not
      significantly different between females and males, that for neck pain in the
      preceding 12 months was significantly higher in females than males. Although
      there was no association between the sagittal alignment of C2-C7 and neck
      symptoms in males or females, a significant correlation between the degenerative
      index and VAS for neck pain on the examination day and in the preceding 12 months
      was seen in females after adjusting for age. The prevalence of and VAS for neck
      pain and stiff shoulder were not significantly different among the three C2-C7
      sagittal alignment groups. CONCLUSION: Although the sagittal alignment of the
      cervical spine was not associated with neck symptoms, degenerative changes were
      associated with the severity of neck pain in females.

PMID- 24570300
TI  - Awareness and use of diagnostic support tools for lumbar spinal stenosis in
      Japan.
AB  - BACKGROUND: Lumbar spinal stenosis (LSS) is a major clinical problem associated
      with back pain, intermittent claudication, leg pain, and leg numbness. Diagnostic
      support tools for LSS such as the self-administered, self-reported history
      questionnaire (SSHQ) and developmental clinical diagnosis support tool (ST) have
      been validated in Japan. However, the degree of awareness and use of these two
      diagnostic support tools for LSS in Japan has not been clarified. The aims of the
      current study were to determine the degree of awareness and use of these two
      diagnostic support tools by Japanese physicians. Furthermore, we compared these
      results among nonorthopedic general practitioner (GP), orthopedic GP, and
      hospital-based orthopedic physicians. METHODS: The LSS Diagnosis Support Tool
      (DISTO) Project was conducted to evaluate the degree of awareness and use of
      these two diagnostic support tools in Japan from 2011 to 2012. A total of 1,811
      answers were obtained from physicians including nonorthopedic general
      practitioners (GP), orthopedic GPs, and hospital-based orthopedic physicians.
      Questions were (1) Do you know about these two diagnostic tools? and (2) If you
      know about these two diagnostic tools, have you used them? RESULTS: The degree of
      awareness of ST and SSHQ was about 30 and 26 % by nonorthopedic GPs, 70 and 46 %
      by orthopedic GPs, and 68 and 41 % by hospital-based orthopedic physicians. The
      degree of awareness of ST and SSHQ by nonorthopedic GPs was significantly lower
      than by orthopedic GPs or hospital-based orthopedic physicians (p < 0.001). For
      physicians who were aware of ST and SSHQ, the degree of use of ST or SSHQ was <50
      % by nonorthopedic GPs, orthopedic GPs, and hospital-based orthopedic physicians.
      CONCLUSIONS: We expect that use of the ST or SSHQ tools in primary care will
      improve the accuracy of diagnosis and lead to improved quality of patient care.
      The low proportion of awareness by nonorthopedic GPs (<30 %) and use by all
      physicians (<50 %) indicate a need to encourage physicians to use ST and SSHQ
      more frequently.

PMID- 24570301
TI  - Variable plant hydraulic conductance.

PMID- 24570302
TI  - The history and reception of Charles Darwin's hypothesis of pangenesis.
AB  - This paper explores Charles Darwin's hypothesis of pangenesis through a popular
      and professional reception history. First published in The Variation of Animals
      and Plants under Domestication (1868), pangenesis stated that inheritance can be
      explained by sub-cellular "gemmules" which aggregated in the sexual organs during
      intercourse. Pangenesis thereby accounted for the seemingly arbitrary absence and
      presence of traits in offspring while also clarifying some botanical and
      invertebrates' limb regeneration abilities. I argue that critics largely
      interpreted Variation as an extension of On the Origin of Species by Means of
      Natural Selection (1859), while pangenesis was an extension of natural selection.
      Contrary to claims that pangenesis was divorced from natural selection by its
      reliance on the inheritance of acquired characters, pangenesis's mid nineteenth
      century reception suggests that Darwin's hypothesis responded directly to
      selection's critics. Using Variation's several editions, periodical reviews, and
      personal correspondence I assess pangenesis popularly, professionally, and
      biographically to better understand Variation's impact on 1860s and 70s British
      evolutionism and inheritance. 

PMID- 24570304
TI  - The history of neurosurgery in Germany.

PMID- 24570303
TI  - Rare mimicry of meningioma: angioleiomyoma of the falx.
AB  - BACKGROUND: Angioleiomyomas (ALMs) are benign soft tissue tumors composed of
      various size vessels with abundant intervening smooth muscles. Intracranial ALMs
      are exceedingly rare with 12 reported cases to date presenting as extracerebral
      masses that mimic cerebral cavernous malformation or meningiomas. OBJECTIVE: We
      report a case of intracranial ALM of the falx cerebri imitating an atypical
      meningioma or hemangiopericytoma. RESULTS AND CONCLUSIONS: Magnetic resonance
      imaging (MRI) features and perfusion-weighted MRI revealed special features that
      may be helpful to distinguish ALMs from meningiomas and should result in the
      consideration of rarer extracerebral tumors like ALMs.

PMID- 24570305
TI  - Frameless nonstereotactic image-guided surgery of supratentorial lesions:
      introduction to a safe and inexpensive technique.
AB  - BACKGROUND: We describe a simple, safe, and inexpensive technique that through
      the comparison of three-dimensional (3D)-rendered magnetic resonance (MR) images
      and real anatomy allows us to navigate and remove brain lesions, including those
      without cortical appearance, by direct recognition of anatomical landmarks.
      Preoperative planning no longer requires the use of fiducials and can therefore
      be performed out a stereotactic setting. METHODS: MR Digital Imaging and
      Communications in Medicine format scans of 93 patients were reconstructed using
      MRIcro freeware for their three-dimensional rendering (3DR). The main location of
      the lesions was rolandic or left temporal, and most of them were without cortical
      appearance (78%). The two-dimensional (2D) sets of images were processed by the
      software to perform a 3DR, thus obtaining a virtual model of the patient's head.
      Using the same 2D sets, the edges of the lesion's images were contoured by the
      region of interest (ROI) tool. In the next step, the ROI was projected onto the
      surface of the virtual model of the patient's head, thus helping to attain the
      best identification of the craniotomy area. MRIcro automatic segmentation
      function, the Brain Extraction Tool (BET), provides a clear 3DR of the cortical
      surface. We used BET to display gyri, sulci, and perilesional vessels to have
      further anatomical landmarks to guide the surgical approach. RESULTS: The lesions
      were accessed through an optimally suited craniotomy. The visual matching of the
      cortical surface with reconstructed 3D images of the cortex permitted a fast
      localization of cortical and subcortical lesions. The major limitation is the
      depth of a lesion deeper than 3 cm. In these cases, the use of frame-based or
      frameless techniques still seems safer and more advantageous. Conclusions: The
      shape recognition of the cortical landmarks was not biased by brain distortion
      because the sulci and cortical vessels almost always had a relationship to each
      other that was not modified by edema or cerebrospinal fluid leakage. This 3DR
      allows us to reconstruct a virtual anatomy in an easy, portable, and inexpensive
      way. In selected cases, this technique represents a valid and safe alternative to
      the use of costly neuronavigation tools and is potentially helpful in developing
      countries.

PMID- 24570306
TI  - Improved magnetic resonance myelography of the cervical spine using image fusion
      and volumetry.
AB  - BACKGROUND AND AIMS: Discrepancies between symptoms and imaging findings may be
      significant in spinal diseases. The relative advantages and disadvantages of
      postmyelographic CT (pmCT) and magnetic resonance myelography (MRM) in measuring
      cervical cerebrospinal fluid dimensions and volumes are poorly understood. This
      study investigated the usefulness of an improved MRM approach and compared its
      findings of dural areas and volumes of normal and pathologic cervical spine
      levels with those obtained by pmCT. MATERIALS AND METHOD: Sixty patients with
      suspected cervical spinal stenosis underwent myelography, pmCT, and an improved
      MRM approach using a dedicated heavily T2-weighted magnetic resonance (MR)
      sequence in combination with image fusion. Cross-sectional areas and volumes of
      the dural sac from C2-3 to C7-T1 were compared for significance of differences
      between mean values. Pearson correlations between pmCT and MRM values were
      analyzed. Then 99% confidence intervals for normal levels and levels with obvious
      stenosis were calculated. RESULTS: For normal cervical levels we found no
      significant differences for both dural areas and volumes between pmCT and MRM.
      For cervical spine levels C3-4 to C6-7 with pathologic alterations, we found
      significant larger areas and volumes on MRM when compared with pmCT but not for
      the levels C2-3 and C7-T1. Both dural area and volume of normal and pathologic
      levels showed strong correlation between pmCT and MRM. We found no overlap
      between 99% confidence intervals for normal levels and stenotic levels.
      CONCLUSIONS: The optimized MRM approach (i.e., a dedicated MRM sequence in
      combination with image fusion) and pmCT demonstrated excellent quantitative
      volumetric agreement. Image fusion with conventional T2 may be used to aid in
      diagnosis.

PMID- 24570307
TI  - Video-assisted thoracoscopic surgery under O-arm navigation system guidance for
      the treatment of thoracic disk herniations: surgical techniques and early
      clinical results.
AB  - This study describes the surgical technique and clinical results of video
      assisted thoracoscopic surgery (VATS) assisted by an O-arm-based navigation
      system, used for the treatment of thoracic disk herniation (TDH). The trend
      toward the use of minimally invasive procedures with endoscopic visualization of
      the thoracic cavity in thoracic spine surgery has evolved. It is difficult to
      develop a new set of visuomotor skills unique to endoscopic procedures and
      understand the three-dimensional (3D) anatomy while performing a two-dimensional
      (2D) imaging procedure. Adding image guidance would have a positive impact on
      these procedures, making them safer and more precise. We report the results of 10
      patients who underwent diskectomy for TDH using VATS assisted by an O-arm-based
      navigation system and describe the surgical technique. The average duration of
      the symptoms was 2.8 years; average operation time, 326.9 minutes; and average
      additional time required for the image guidance surgery using the O-arm-based
      navigation, ~ 29.4 minutes. No complications occurred during the surgical
      procedure or the immediate postoperative period. The advantages of using
      navigational assistance during the surgical procedure include better
      visualization of the operative field, more accurate surgical planning, and
      optimization of the surgical approach involving the establishment of the correct
      drilling trajectory and safe decompression of the spinal cord, as well as the
      possibility of intraoperative control of bone resection. 

PMID- 24570308
TI  - Stereotactic anatomy of the human subthalamic nucleus: providing coordinates for
      accurate electrode placement.
AB  - BACKGROUND AND STUDY AIMS: Stereotactic targeting of the subthalamic nucleus
      (STN) for insertion of deep brain stimulation (DBS) electrodes became popular in
      the last two decades. We present a study focused on the detailed stereotactic
      anatomy of the STN with respect to its targeting. MATERIAL AND METHODS: We used
      cerebral magnetic resonance (MR) images from 26 patients (50 STNs) for the
      imaging study. The material of the anatomical study consisted of 24 cerebral
      hemispheres (24 STNs) from 16 normal human brains. We measured and analyzed the
      X, X', Y, Y', and Z, Z' stereotactic coordinates of the STN at specific
      clinically important transverse, coronal, and sagittal planes. RESULTS: The STN
      extended almost 1.5 mm more lateral and almost 1 mm more posterior in patients <
      60 years of age. The Y coordinate was more posterior and the X coordinate more
      lateral on MRI than in anatomical specimens. The left STN was located more
      lateral than the right STN. Analyzing our data we found a standard coronal zone
      1.1 mm wide (zone T), a standard coronal plane (thus providing the most accurate
      Y target coordinate, plane M), and a standard transverse area (area C) for
      accurate right STN targeting. CONCLUSIONS: Our study offers new insights into the
      stereotactic anatomy of the human STN. These data should be taken into account if
      performing STN DBS.

PMID- 24570309
TI  - Radio-anatomic measurements and statistical generation of a safe surgical
      corridor to enter the ventricular trigone while avoiding injury to the optic
      radiations.
AB  - OBJECTIVE: To find a safe operative corridor to the ventricular trigone avoiding
      injury to the optic radiations (ORs). METHODS: In 24 adult hemispheres,
      dimensions of the atrium, height of the OR, and the cortex-to-atrium distance
      were measured. Superior parietal lobule (SPL), parieto-occipital sulcus (POS),
      and middle temporal gyrus (MTG) traced approaches were used to measure maximum
      safe angles to enter the atrium without traversing the OR. A statistical
      algorithm was generated using these measurements to predict the height of the OR
      and safe angles from measurements from MR imaging of five test hemispheres.
      Statistically calculated angles were compared with measured angles from
      dissection. RESULTS: Mean length and height of atrium, height of OR, and cortico
      atrium distances were 2.07 cm, 3.36 cm, 2.53 cm, and 4.11 cm, respectively. The
      height of the atrium influenced the height of the OR significantly (p < 0.0001).
      The height of the dilated and small atrium was > 4.5 cm (> 95th percentile) and <
      2 cm (< 5th percentile), respectively. For the SPL approach, the mean sagittal
      angle was 15.75 to 41.04 degrees; the mean coronal angle was - 17.08 to 14.92
      degrees. For the POS approach, the mean sagittal angle was 51.29 to 70.1 degrees;
      the mean coronal angle was -8.63 to 17.22 degrees. Mean calculated height
      (statistically) of the OR was 0.29 mm above the mean observed height
      (dissection). The calculated angles and observed angles were very similar when
      tested for a variability of +/- 2 degrees. CONCLUSION: The height of the normal
      atrium was 2.58 cm (height of atrium to height of OR ratio was 1:0.76). An
      operative corridor to the atrium without damaging the OR can be calculated from
      MR imaging of the brain.

PMID- 24570310
TI  - Smart trepanation system: preclinical analysis of safety, efficiency, and user
      satisfaction.
AB  - BACKGROUND/OBJECTIVE: To reduce the risk of dural tears during craniotomies and
      the associated complications, we developed the Smart Trepanation System (STS)
      that provides an image- and sensor-based automatic control of the cutting depth
      of a manually guided soft tissue preserving saw. This article presents the
      results of an initial user-centered evaluation. METHODS: Interactive usability
      tests with six neurosurgeons were conducted. Resection time and accuracy were
      recorded in a standardized laboratory setting and compared with a standard
      craniotome. User satisfaction and subjective workload were assessed using the
      National Aeronautics and Space Administration Task Load Index scale and a
      questionnaire regarding intuitiveness, fault tolerance, learnability, and user
      satisfaction. RESULTS: The mean resection time after getting used to the STS was
      36.4 +/- 9.2 second longer than with the conventional craniotome. All task load
      indexes except for the temporal demand were rated higher when using the STS, but
      all were rated smaller than 3 and thus classified as only a small extra task
      load. The questionnaire showed that the system is not only feasible but also
      accepted by surgeons and that the user interaction seems to be designed as
      intuitive, fault tolerant, and easy to learn. CONCLUSION: Although the
      conventional craniotome seems to perform a trepanation faster and with less
      workload, the advantage of performing a dura-preserving trepanation with
      significantly smaller cutting gaps outweighs those disadvantages. For validation
      of those promising in vitro results, further studies have to be conducted in a
      fresh human cadaver model or in a clinical setting.

PMID- 24570311
TI  - The beginning of a new journey.

PMID- 24570312
TI  - Clinics in diagnostic imaging (151). Acromioclavicular joint geyser sign with
      chronic full-thickness supraspinatus tendon (SST) tear.
AB  - An 82-year-old man presented with neck pain, right upper limb radiculopathy and
      right shoulder pain. Physical examination revealed a soft lump over the right
      shoulder joint, as well as reduced range of shoulder movements. On magnetic
      resonance imaging, the soft lump was shown to be a cystic mass over the
      acromioclavicular joint and was related to a full-thickness supraspinatus tendon
      tear. This is the classic geyser sign. The pathophysiology and clinical features
      of the geyser sign, and its imaging features with various imaging modalities, are
      discussed. 

PMID- 24570313
TI  - Academy of Medicine-Ministry of Health Clinical Practice Guidelines: assessment
      and management of infertility at primary healthcare level.
AB  - The Academy of Medicine (AMS) and Ministry of Health (MOH) have developed the
      clinical practice guidelines on Assessment and Management of Infertility at
      Primary Healthcare Level to provide doctors and patients in Singapore with
      evidence-based treatment for infertility. This article reproduces the
      introduction and executive summary (with recommendations from the guidelines)
      from the AMS-MOH clinical practice guidelines on Assessment and Management of
      Infertility at Primary Healthcare Level, for the information of SMJ readers.
      Chapters and page numbers mentioned in the reproduced extract refer to the full
      text of the guidelines, which are available from the Ministry of Health website:
      http://www.moh.gov.sg/content/moh_web/healthprofessionalsportal/doctors/guideline
      /cpg_medical/2013/cpgmed_infertility.html. The recommendations should be used
      with reference to the full text of the guidelines. Following this article are
      multiple choice questions based on the full text of the guidelines. 

PMID- 24570315
TI  - The music listening preferences and habits of youths in Singapore and its
      relation to leisure noise-induced hearing loss.
AB  - INTRODUCTION: Noise-induced hearing loss (NIHL) is a preventable condition, and
      much has been done to protect workers from it. However, thus far, little
      attention has been given to leisure NIHL. The purpose of this study is to
      determine the possible music listening preferences and habits among young people
      in Singapore that may put them at risk of developing leisure NIHL. METHODS: In
      our study, the proportion of participants exposed to > 85 dBA for eight hours a
      day (time-weighted average) was calculated by taking into account the daily
      number of hours spent listening to music and by determining the average sound
      pressure level at which music was listened to. RESULTS: A total of 1,928 students
      were recruited from Temasek Polytechnic, Singapore. Of which, 16.4% of
      participants listened to portable music players with a time-weighted average of >
      85 dBA for 8 hours. On average, we found that male students were more likely to
      listen to music at louder volumes than female students (p < 0.001). We also found
      that the Malay students in our study listened to louder music than the Chinese
      students (p < 0.001). CONCLUSION: We found that up to one in six young persons in
      Singapore is at risk of developing leisure NIHL from music delivered via
      earphones. As additional risks due to exposure to leisure noise from other
      sources was not taken into account, the extent of the problem of leisure NIHL may
      be even greater. There is a compelling need for an effective leisure noise
      prevention program among young people in Singapore.

PMID- 24570316
TI  - Evaluation of the patient safety Leadership Walkabout programme of a hospital in
      Singapore.
AB  - INTRODUCTION: The Patient Safety Leadership Walkabout (PSLWA) programme is a
      commonly employed tool in the West, in which senior leaders visit sites within
      the hospital that are involved in patient care to talk to healthcare staff about
      patient safety issues. As there is a lack of perspective regarding PSLWA in Asia,
      we carried out an evaluation of its effectiveness in improving the patient safety
      culture in Tan Tock Seng Hospital, Singapore. METHODS: A mixed methods analysis
      approach was used to review and evaluate all documents, protocols, meeting
      minutes, post-walkabout surveys, action plans and verbal feedback pertaining to
      the walkabouts conducted from January 2005 to October 2012. RESULTS: A total of
      321 patient safety issues were identified during the study period. Of these, 308
      (96.0%) issues were resolved as of November 2012. Among the various categories of
      issues raised, issues related to work environment were the most common (45.2%).
      Of all the issues raised during the walkabouts, 72.9% were not identified through
      other conventional methods of error detection. With respect to the hospital's
      patient safety culture, 94.8% of the participants reported an increased awareness
      in patient safety and 90.2% expressed comfort in openly and honestly discussing
      patient safety issues. CONCLUSION: PSLWA serves as a good tool to uncover latent
      errors before actual harm reaches the patient. If properly implemented, it is an
      effective method for engaging leadership, identifying patient safety issues, and
      supporting a culture of patient safety in the hospital setting.

PMID- 24570314
TI  - Comparison between elderly inpatient fallers with and without dementia.
AB  - INTRODUCTION: This study aimed to examine the various factors associated with
      inpatient falls among patients with and without dementia in a hospital setting.
      METHODS: This was a retrospective one-year study using data collected from
      Singapore General Hospital's electronic reporting system for inpatient falls.
      RESULTS: In the study period, 298 patients aged >= 65 years fell during their
      hospital stay. The majority of the patients (n = 248) did not have dementia. In
      our study, fallers with dementia were more likely to use ambulatory aids, be
      visually impaired and have urinary incontinence. More patients with dementia than
      those without had a history of previous falls, and were placed on fall precaution
      with restricted freedom of movement, which at times, included restraints.
      However, the difference between patients who were put on restraints and those who
      were allowed to move freely was not statistically significant. The majority of
      falls in both groups occurred at the bedside. We found that fallers without
      dementia were more likely to fall during the morning shift, whereas fallers with
      dementia were more likely to fall during the night shift. Fallers with dementia
      were more likely to be confused at the time of the fall. CONCLUSION: In our
      study, we found that fallers with dementia were more likely to have visual
      impairment, have urinary incontinence, use walking aids, and to be confused and
      physically restrained at the time of the fall. The fallers without dementia in
      our study may have undiagnosed dementia.

PMID- 24570317
TI  - Prevalence of obesity and its associated risk factors among Chinese adults in a
      Malaysian suburban village.
AB  - INTRODUCTION: Obesity is a major modifiable risk factor associated with most
      chronic diseases. The aim of this study was to determine the prevalence of
      obesity, and its associated risk factors, among apparently healthy Chinese adults
      in a Malaysian suburban village. METHODS: This was a cross-sectional study
      conducted among the Chinese residents in Seri Kembangan New Village, Klang
      Valley, Selangor, Malaysia. Convenience sampling was used for the selection of
      participants. Body weight, height, waist and hip circumferences, and blood
      pressure were measured. Fasting venous plasma was drawn for the measurement of
      fasting glucose level and lipid profile. Data on sociodemographic factors,
      dietary habits, physical activity, perceived stress level and sleep duration were
      collected using interviewer-administered, pretested and validated questionnaires.
      RESULTS: Among the 258 Chinese residents (mean age 41.4 +/- 10.0 years)
      recruited, the prevalence of obesity was 40%. The obese participants had
      significantly higher mean blood pressure, and triglyceride and fasting plasma
      glucose levels than the non-obese participants (p < 0.05). The obese participants
      also had a significantly lower high-density lipoprotein cholesterol level than
      the non-obese participants. Logistic regression analysis showed that drinking soy
      milk (adjusted odds ratio [OR] 0.447; 95% confidence interval [CI] 0.253-0.787; p
      < 0.05) and the perception that a balanced diet consists mainly of vegetables
      (adjusted OR 0.440; 95% CI 0.215-0.900; p < 0.05) were associated with a reduced
      risk of obesity. The risk of obesity was higher in younger participants (adjusted
      OR 2.714; 95% CI 1.225-6.011; p < 0.05). CONCLUSION: The prevalence of obesity
      was high among the apparently healthy suburban Chinese. Our findings suggest that
      soy milk consumption and the perception that a balanced diet consists mainly of
      vegetables are associated with a lower risk of developing obesity in this
      population.

PMID- 24570319
TI  - Dr Wu Lien-teh: modernising post-1911 China's public health service.

PMID- 24570318
TI  - Adherence to highly active antiretroviral therapy in a tertiary care hospital in
      West Bengal, India.
AB  - INTRODUCTION: The introduction of highly active antiretroviral therapy (HAART)
      for the treatment of human immunodeficiency virus (HIV) infection and acquired
      immunodeficiency syndrome (AIDS) has led to the reduction of mortality and the
      improvement of the quality of life of people living with HIV/AIDS (PLWHA). The
      present study was conducted to determine the pattern of adherence to HAART among
      PLWHA, and to assess the factor(s) affecting nonadherence, if any. METHODS: This
      study was a hospital-based analytical, cross-sectional epidemiological study
      conducted between July and October 2011. A total of 370 adult HIV-positive
      patients registered in the Antiretroviral Therapy Centre of Burdwan Medical
      College and Hospital, West Bengal, India, were included. Nonadherence was defined
      as missing at least a single dose of medicine within the last four days. Data was
      analysed using the Statistical Package for the Social Sciences version 19.0 (IBM
      Corp, Armonk, NY, USA). RESULTS: A total of 87.6% of patients were found to be
      adherent to HAART. Principal causes of nonadherence were forgetting to take
      medicine (70.2%), being away from home (65.2%), and busyness with other things
      (64.7%). Multivariate logistic regression analysis revealed that nonadherence was
      significantly associated with a positive family history of HIV/AIDS (odds ratio
      [OR] 16; 95% confidence interval [CI] 2.2-114.3; p = 0.01), occurrence of side
      effects with HAART (OR 9.81; 95% CI 1.9-51.7; p = 0.01) and employment (OR 5.93;
      95% CI 1.5-23.2; p = 0.01). CONCLUSION: Although overall adherence was high, the
      factors that affect nonadherence can be addressed with proper counselling and
      motivation of patients and their family members. Adherence to HAART could delay
      the progression of this lethal disease and minimise the risk of developing drug
      resistance.

PMID- 24570320
TI  - First transcatheter aortic valve implantation for severe pure aortic
      regurgitation in Asia.
AB  - Transcatheter aortic valve implantation (TAVI) has become the standard of care
      for inoperable patients with symptomatic severe aortic stenosis (AS), and an
      alternative to open aortic valve replacement for patients at high surgical risk.
      TAVI has also been performed in several groups of patients with off-label
      indications such as severe bicuspid AS, and as a valve-in-valve therapy for a
      degenerated surgical bioprosthesis. Although TAVI with CoreValve(r) prosthesis is
      technically challenging, and global experience in the procedure is limited, the
      procedure could be a treatment option for well-selected patients with severe pure
      aortic regurgitation (AR). Herein, we report Asia's first case of TAVI for severe
      pure AR in a patient who was at extreme surgical risk, with good clinical outcome
      at six months. 

PMID- 24570323
TI  - Phosphate-independent utilization of phosphonoacetic acid as sole phosphorus
      source by a psychrophilic strain of Geomyces pannorum P15.
AB  - A psychrophilic fungal strain of Geomyces pannorum P15 was screened for its
      ability to utilize a range of synthetic and natural organophosphonate compounds
      as the sole source of phosphorus, nitrogen, or carbon. Only phosphonoacetic acid
      served as a phosphorus source for microbial growth in phosphate-independent
      manner. Substrate metabolism did not lead to extracellular release of inorganic
      phosphate. No phosphonate metabolizing enzyme activity was detectable in cell
      free extracts prepared from Geomyces biomass pregrown on 2 mmol/L phosphonoacetic
      acid.

PMID- 24570324
TI  - Sex differences in color preferences transcend extreme differences in culture and
      ecology.
AB  - At first glance, color preferences might seem to be the most subjective and
      context-dependent aspects of color cognition. Yet they are not. The present study
      compares color preferences of women and men from an industrialized and a remote,
      nonindustrialized culture. In particular, we investigated preferences in
      observers from Poland and from the Yali in Papua, respectively. Not surprisingly,
      we found that color preferences clearly differed between the two communities and
      also between sexes. However, despite the pronounced cultural differences, the way
      in which men and women differed from each other was almost the same in both
      cultures. At the same time, this sexual contrast was not specific to biological
      components of color vision. Our results reveal a pattern of sexual dimorphism
      that transcends extreme differences in culture and ecology. They point toward
      strong cross-cultural constraints beyond the biological predispositions of nature
      and the cultural particularities of nurture.

PMID- 24570325
TI  - Point mutation of the xylose reductase (XR) gene reduces xylitol accumulation and
      increases citric acid production in Aspergillus carbonarius.
AB  - Aspergillus carbonarius accumulates xylitol when it grows on D-xylose. In fungi,
      D-xylose is reduced to xylitol by the NAD(P)H-dependent xylose reductase (XR).
      Xylitol is then further oxidized by the NAD(+)-dependent xylitol dehydrogenase
      (XDH). The cofactor impairment between the XR and XDH can lead to the
      accumulation of xylitol under oxygen-limiting conditions. Most of the XRs are
      NADPH dependent and contain a conserved Ile-Pro-Lys-Ser motif. The only known
      naturally occurring NADH-dependent XR (from Candida parapsilosis) carries an
      arginine residue instead of the lysine in this motif. In order to overcome
      xylitol accumulation in A. carbonarius a Lys-274 to Arg point mutation was
      introduced into the XR with the aim of changing the specificity toward NADH. The
      effect of the genetic engineering was examined in fermentation for citric acid
      production and xylitol accumulation by using D-xylose as the sole carbon source.
      Fermentation with the mutant strain showed a 2.8-fold reduction in xylitol
      accumulation and 4.5-fold increase in citric acid production compared to the wild
      type strain. The fact that the mutant strain shows decreased xylitol levels is
      assumed to be associated with the capability of the mutated XR to use the NADH
      generated by the XDH, thus preventing the inhibition of XDH by the high levels of
      NADH and ensuring the flux of xylose through the pathway. This work shows that
      enhanced production of citric acid can be achieved using xylose as the sole
      carbon source by reducing accumulation of other by-products, such as xylitol. 

PMID- 24570326
TI  - Calcium/calmodulin-dependent kinases are involved in growth, thermotolerance,
      oxidative stress survival, and fertility in Neurospora crassa.
AB  - Calcium/calmodulin-dependent kinases (Ca(2+)/CaMKs) are Ser/Thr protein kinases
      that respond to change in cytosolic free Ca(2+) ([Ca(2+)]c) and play multiple
      cellular roles in organisms ranging from fungi to humans. In the filamentous
      fungus Neurospora crassa, four Ca(2+)/CaM-dependent kinases, Ca(2+)/CaMK-1 to 4,
      are encoded by the genes NCU09123, NCU02283, NCU06177, and NCU09212,
      respectively. We found that camk-1 and camk-2 are essential for full fertility in
      N. crassa. The survival of ?camk-2 mutant was increased in induced
      thermotolerance and oxidative stress conditions. In addition, the ?camk-1 ?camk
      2, ?camk-4 ?camk-2, and ?camk-3 ?camk-2 double mutants display slow growth
      phenotype, reduced aerial hyphae, decreased thermotolerance, and increased
      sensitivity to oxidative stress, revealing the genetic interactions among these
      kinases. Therefore, Ca(2+)/CaMKs are involved in growth, thermotolerance,
      oxidative stress tolerance, and fertility in N. crassa. 

PMID- 24570327
TI  - Prevention of contrast-induced nephropathy with prostaglandin E1 in high-risk
      patients undergoing percutaneous coronary intervention.
AB  - PURPOSE: Contrast-induced nephropathy (CIN) is an important complication in the
      use of iodinated contrast media. The present study aimed to assess the safety and
      efficacy of prostaglandin E1 (PGE1) in prevention of CIN in patients with high
      risk factors undergoing percutaneous coronary intervention (PCI). METHODS: The
      study group consisted of 163 patients who had undergone a coronary intervention
      procedure between January 1, 2012 and October 31, 2012. Study participants were
      randomly assigned to either the PGE1 group (82 patients) or the control group (81
      patients). Patients in the PGE1 group received PGE1 intravenous infusion of 20
      ng/kg/min for 6 h before and after the administration of contrast media. The
      control group received 0.9 % sodium chloride solution for routine hydration only.
      A nonionic, low-osmolality contrast agent was used in our laboratory at this
      time. Serum creatinine (Scr) values and estimated glomerular filtration rate were
      measured before and within 48 h of the administration of contrast agents. CIN was
      defined as an increase of >=0.5 mg/dL or >= a 25 % increase in Scr concentrations
      over baseline within 48 h of angiography. RESULTS: The amount of contrast agent
      administered was similar for the PGE1 and control groups (156 +/- 63 vs. 161 +/-
      68 mL, P > 0.05). The incidence of CIN was lower in the PGE1 group than in the
      control group (3.7 vs. 11.1 %, P < 0.05). No serious adverse effects were
      observed. CONCLUSIONS: In patients with high-risk factors undergoing PCI, the use
      of PGE1 for prevention of CIN is safe and efficacious.

PMID- 24570329
TI  - Exploring factors that have caused a decrease in surgical manpower in Taiwan.
AB  - The decreasing availability of surgical physicians is a concern in most
      countries. In the past decade, total physician manpower in Taiwan increased by
      12%, but the number of surgical physicians decreased by 11%. Medical students are
      not inclined to choose surgery as a career--this study examines the factors
      involved in students' career choices. This study was conducted from January 2011
      to April 2011. In total, 401 interns successfully completed questionnaires; this
      population makes up 34% of all interns in Taiwan. The structural questionnaire
      was designed to investigate factors affecting specialty decisions, with
      additional open-ended questions to investigate students' preferences in career
      specialty. Based on the research findings, the 3 most relevant factors in
      decreasing order of priority are personal interest, career-oriented lifestyle,
      and specialty characteristics (including workload and stress). For students
      likely to become surgical physicians, concerns about the work environment include
      the balance between work and family, wages that are incompatible with the
      workload, and the shortage of manpower on duty. Addressing the following concerns
      would increase medical students' likelihood of choosing a career in surgery: the
      need for a facilitator to help mitigate medical disputes and legal problems,
      decreased work hours, and decreased on-call duty hours. This study shows both
      motivating and discouraging factors affecting whether medical students choose
      surgery as a career. The purpose of this study is to strengthen the incentives
      for medical students to choose surgery as a career and to minimize the influence
      of factors that negatively affect such a choice.

PMID- 24570328
TI  - Chronic respiratory conditions in a cohort of metropolitan fire-fighters:
      associations with occupational exposure and quality of life.
AB  - OBJECTIVES: To assess the prevalence of chronic respiratory conditions in
      metropolitan fire-fighters and to study associations between occupational
      exposure, use of respiratory protection and health-related quality of life
      (HRQoL) in fire-fighters with and without chronic respiratory conditions.
      METHODS: Cross-sectional cohort analysis: Respiratory symptoms, medical
      conditions, occupational tasks and exposures and consistency of using respiratory
      protection were inquired by questionnaire. The SF12((r))V2 Health Survey was used
      to measure physical (PCS-12) and mental (MCS-12) HRQoL. Fire-fighters were
      categorised in subgroups: asthma; COPD/emphysema/chronic bronchitis; no chronic
      respiratory conditions; and as being 'not involved' or 'involved' in fire
      fighting tasks, the latter further categorised as 'consistent' or 'inconsistent'
      use of respiratory protection. PCS-12 and MCS-12 scores were compared between
      subgroups and categories using linear regression. RESULTS: Five hundred and
      seventy fire-fighters were analysed, 24 (4%) fulfilled the criteria for asthma,
      39 (7%) for COPD/emphysema/chronic bronchitis. Fire-fighters with asthma were
      older than those in the other two subgroups and had been employed in the fire
      service longer. Respiratory subgroups did not differ in their involvement in fire
      fighting tasks. Ninety-one percent of fire-fighters reported relevant
      occupational exposure in the past year. Mean PCS-12 scores for fire-fighters with
      no chronic respiratory conditions, asthma and COPD/emphysema/bronchitis were 52.0
      (SD 6.9), 47.0 (8.5) and 48.1 (9.4). For PCS-12 (but not for MCS-12), interaction
      between having a chronic respiratory condition and inconsistent use of
      respiratory protection during fire knockdown was observed (p < 0.001).
      CONCLUSIONS: Ten percent of metropolitan fire-fighters reported underlying
      chronic respiratory conditions. Presence of such a condition in combination with
      suboptimal protection from inhaled exposures may lead to poorer physical HRQoL.

PMID- 24570330
TI  - Phase II clinical trial of PM00104 (Zalypsis((r))) in urothelial carcinoma
      patients progressing after first-line platinum-based regimen.
AB  - PURPOSE: This exploratory phase II clinical trial evaluated the antitumor
      activity, safety profile and pharmacokinetics of PM00104 (Zalypsis((r))) 3
      mg/m(2) 1 h every 3-week intravenous infusion in patients with advanced and/or
      metastatic urothelial carcinoma progressing after first-line platinum-based
      chemotherapy. METHODS: The primary efficacy end point was the disease control
      rate (DCR), defined as the percentage of patients with confirmed objective
      response or progression-free at 3 months, according to the response evaluation
      criteria in solid tumors. RESULTS: In a first stage (n = 19 patients evaluable
      for efficacy), only one patient achieved DCR (stable disease as best response and
      progression-free survival of 3.1 months). According to the 2-stage design used,
      the primary efficacy objective was unmet, and therefore, the trial was finalized
      without opening the second stage. The most common adverse events related to
      PM00104 were fatigue, anorexia, nausea, troponin I increase and neutropenia,
      which were transient and manageable with dose modifications or administration
      delays. Mean PK results (Cmax = 48.57 MUg/l and area under the curve (AUC) =
      154.97 h MUg/l) were similar to those observed in a previous phase I trial
      evaluating the same dose and schedule. Few troponin I concentrations were higher
      than 0.10 ng/ml, and none of them were related to parameters of PM00104 exposure
      such as AUC or Cmax. CONCLUSIONS: No recommendation is given for further
      evaluation of PM00104 as single-agent treatment of patients with pretreated
      advanced and/or metastatic urothelial carcinoma. No new safety signals were
      observed.

PMID- 24570331
TI  - Role of CD30 targeting in malignant lymphoma.
AB  - CD30 is an important therapeutic target for the treatment of malignant lymphomas.
      CD30 is a member of the TNF cell receptor superfamily and is highly expressed in
      a variety of lymphoma subsets, including Hodgkin lymphoma and anaplastic large
      cell lymphoma. Initial studies evaluated the safety and efficacy of several
      monoclonal antibodies targeting CD30, with limited success. More recently, the
      anti-CD30 drug-conjugate brentuximab vedotin produced high response rates with an
      excellent safety profile. These results lead to the approval of brentuximab
      vedotin for the treatment of patients with relapsed Hodgkin lymphoma and
      anaplastic large cell lymphoma. Current studies are focusing on incorporating
      brentuximab vedotin in front-line regimens and expanding its potential clinical
      utility in other CD30-expressing malignancies.

PMID- 24570332
TI  - Correlative study of squash smear cytology with histopathology in a rare case of
      anaplastic giant cell ependymoma of the pineal.
AB  - Anaplastic giant cell ependymoma (AGCE) is a very rare neoplasm. Its cytological
      features, helpful for the intraoperative diagnosis, have been reported only once.
      AGCE is characterized by giant cells with intranuclear inclusions, besides other
      findings, observable in ependymal neoplasms, such as intracytoplasmic vacuoles,
      epithelial and glial features of the tumor cells and ependymal pseudorosettes.
      These findings can be detected also in intraoperative squash smear. Herein we
      describe a pineal AGCE, highlighting the cytological and histological
      correlations and underlining some useful diagnostic clues of this unusual entity.

PMID- 24570334
TI  - Presentation and validation of "The Learning Game," a tool to study associative
      learning in humans.
AB  - This article presents a 3-D science-fiction-based videogame method to study
      learning, and two experiments that we used to validate it. In this method,
      participants are first trained to respond to enemy spaceships (Stimulus 2, or S2)
      with particular keypresses, followed by transport to a new context (galaxy),
      where other manipulations can occur. During conditioning, colored flashing lights
      (Stimulus 1, or S1) can predict S2, and the response attached to S2 from the
      prior phase comes to be evoked by S1. In Experiment 1 we demonstrated that, in
      accord with previous findings from animals, conditioning in this procedure was
      positively related to the ratio of the time between trials to the time within a
      trial. Experiment 2 demonstrated the phenomena of extinction, timing, and
      renewal. Responding to S1 was slightly lost with a context change, and diminished
      over trials in the absence of S2. On early extinction trials, responding during
      S1 declined after the time that S2 normally occurred. Extinguished responding to
      S1 recovered robustly with a context change. 

PMID- 24570335
TI  - Measuring mechanical pain: the refinement and standardization of pressure pain
      threshold measurements.
AB  - Pain thresholds are widely used in behavioral research, but unlike other pain
      modalities, a standardized assessment of pressure pain remains a challenge. In
      this research, we describe the application of an automatic pressure algometer
      with a linear increase in force. Ergonomically designed fixation devices were
      developed to increase the accuracy and to shorten the time of each measurement.
      Ten healthy volunteers were included in a pilot study to test the algometry
      method. Pressure pain thresholds (PPTs) were investigated over 2 experimental
      days in three nonconsecutive runs at 29 measurement sites. During the experiment,
      subjects reported their subjective sleepiness, level of state-anxiety,
      psychological status and the perceived pain intensity of each measurement. Pain
      intensity ratings indicate that instructions were followed. State-anxiety and
      subjective sleepiness levels were low throughout the experiment. The method has
      proven to be suitable for standardized PPT measurements across the body in an
      ergonomic, safe, and user-friendly fashion. 

PMID- 24570333
TI  - Endothelin receptor polymorphisms in the cardiovascular system: potential
      implications for therapy and screening.
AB  - Since its discovery in 1988, the endothelin system has been employed in multiple
      physiological and pathological roles. Endothelin-1 (ET-1) is not only a major
      regulator of vascular tone and cardiac contractility but also exerts mitogenic
      effects and is involved in inflammatory responses. ET-1 acts via two endothelin
      receptors located mainly on smooth muscle and endothelial cells through complex
      intracellular pathways differing between receptors and cell types. Polymorphisms
      of the endothelin receptor A have been associated not only with the risk in
      pulmonary arterial hypertension (PAH), systolic heart failure and systemic
      hypertension but are also of prognostic significance in dilated cardiomyopathy.
      Polymorphisms of endothelin receptors might lead to altered endothelin signaling
      and influence the response to endothelin receptor antagonist therapy in PAH in
      light of pharmacogenetics. This review will summarize the role of ET-1 within
      major cardiovascular pathologies and discuss endothelin receptor polymorphisms
      with special emphasis on potential therapeutic and screening implications. 

PMID- 24570336
TI  - Absolute quantification of perfusion by dynamic susceptibility contrast MRI using
      Bookend and VASO steady-state CBV calibration: a comparison with pseudo
      continuous ASL.
AB  - OBJECTIVE: Dynamic susceptibility contrast MRI (DSC-MRI) tends to return elevated
      estimates of cerebral blood flow (CBF) and cerebral blood volume (CBV). In this
      study, subject-specific calibration factors (CFs), based on steady-state CBV
      measurements, were applied to rescale the absolute level of DSC-MRI CBF.
      MATERIALS AND METHODS: Twenty healthy volunteers were scanned in a test-retest
      approach. Independent CBV measurements for calibration were accomplished using a
      T1-based contrast agent steady-state method (referred to as Bookend), as well as
      a blood-nulling vascular space occupancy (VASO) approach. Calibrated DSC-MRI was
      compared with pseudo-continuous arterial spin labeling (pCASL). RESULTS: For
      segmented grey matter (GM) regions of interests (ROIs), pCASL-based CBF was 63 +/
      11 ml/(min 100 g) (mean +/- SD). Nominal CBF from non-calibrated DSC-MRI was 277
      +/- 61 ml/(min 100 g), while calibrations resulted in 56 +/- 23 ml/(min 100 g)
      (Bookend) and 52 +/- 16 ml/(min 100 g) (VASO). Calibration tended to eliminate
      the overestimation, although the repeatability was generally moderate and the
      correlation between calibrated DSC-MRI and pCASL was low (r < 0.25). However,
      using GM instead of WM ROIs for extraction of CFs resulted in improved
      repeatability. CONCLUSION: Both calibration approaches provided reasonable
      absolute levels of GM CBF, although the calibration methods suffered from low
      signal-to-noise ratio, resulting in weak repeatability and difficulties in
      showing high degrees of correlation with pCASL measurements.

PMID- 24570337
TI  - Pilot study of Iopamidol-based quantitative pH imaging on a clinical 3T MR
      scanner.
AB  - OBJECTIVE: The objective of this study was to show the feasibility to perform
      Iopamidol-based pH imaging via clinical 3T magnetic resonance imaging (MRI) using
      chemical exchange saturation transfer (CEST) imaging with pulse train
      presaturation. MATERIALS AND METHODS: The pulse train presaturation scheme of a
      CEST sequence was investigated for Iopamidol-based pH measurements using a 3T
      magnetic resonance (MR) scanner. The CEST sequence was applied to eight tubes
      filled with 100-mM Iopamidol solutions with pH values ranging from 5.6 to 7.0.
      Calibration curves for pH quantification were determined. The dependence of pH
      values on the concentration of Iopamidol was investigated. An in vivo measurement
      was performed in one patient who had undergone a previous contrast-enhanced
      computed tomography (CT) scan with Iopamidol. The pH values of urine measured
      with CEST MRI and with a pH meter were compared. RESULTS: In the measured pH
      range, pH imaging using CEST imaging with pulse train presaturation was possible.
      Dependence between the pH value and the concentration of Iopamidol was not
      observed. In the in vivo investigation, the pH values in the human bladder
      measured by the Iopamidol CEST sequence and in urine were consistent. CONCLUSION:
      Our study shows the feasibility of using CEST imaging with Iopamidol for
      quantitative pH mapping in vitro and in vivo on a 3T MR scanner.

PMID- 24570338
TI  - Delayed hepatic signal recovery on ferucarbotran-enhanced magnetic resonance
      images in a rat model with regional liver irradiation.
AB  - OBJECT: To determine whether superparamagnetic iron oxide (SPIO)-enhanced
      magnetic resonance (MR) imaging could demonstrate signal recovery delay in
      irradiated areas of rat livers. We also investigated the relationship between MR
      imaging and histological findings. MATERIALS AND METHODS: Twelve rats received 20
      MUmol iron/kg of SPIO followed by X-irradiation to the right upper abdomen 4 h
      later. Radiation doses were 0, 50 and 70 Gy. Hepatic signals were assessed on
      unenhanced T 2 (*) -weighted images for up to 7 days using a 9.4-Tesla scanner.
      The livers were excised on day 7 and examined histologically. RESULTS: Normalized
      relative signal intensity of 70 Gy-irradiated right liver lobe (2.36 +/- 0.22)
      and 50 Gy-irradiated right liver lobe (2.37 +/- 0.46) was significantly lower
      than that of the non-irradiated right liver lobe (4.04 +/- 0.28) on day 7,
      respectively (p < 0.05). Pearson product-moment correlation coefficient between
      relative intensity of the liver and the number of hepatic iron deposits was 
      0.588 (p < 0.01). CONCLUSION: Superparamagnetic iron oxide-enhanced MR imaging
      could demonstrate signal recovery delay in irradiated areas of rat livers. It
      seems that the signal recovery delay in irradiated areas was due to SPIO-derived
      iron deposition. Hepatic signal recovery could be a novel diagnostic marker for
      delineation of irradiated areas.

PMID- 24570340
TI  - Evaluation of estimation methods and power of tests of discrete covariates in
      repeated time-to-event parametric models: application to Gaucher patients treated
      by imiglucerase.
AB  - Analysis of repeated time-to-event data is increasingly performed in
      pharmacometrics using parametric frailty models. The aims of this simulation
      study were (1) to assess estimation performance of Stochastic Approximation
      Expectation Maximization (SAEM) algorithm in MONOLIX, Adaptive Gaussian
      Quadrature (AGQ), and Laplace algorithm in PROC NLMIXED of SAS and (2) to
      evaluate properties of test of a dichotomous covariate on occurrence of events.
      The simulation setting is inspired from an analysis of occurrence of bone events
      after the initiation of treatment by imiglucerase in patients with Gaucher
      Disease (GD). We simulated repeated events with an exponential model and various
      dropout rates: no, low, or high. Several values of baseline hazard model,
      variability, number of subject, and effect of covariate were studied. For each
      scenario, 100 datasets were simulated for estimation performance and 500 for test
      performance. We evaluated estimation performance through relative bias and
      relative root mean square error (RRMSE). We studied properties of Wald and
      likelihood ratio test (LRT). We used these methods to analyze occurrence of bone
      events in patients with GD after starting an enzyme replacement therapy. SAEM
      with three chains and AGQ algorithms provided good estimates of parameters much
      better than SAEM with one chain and Laplace which often provided poor estimates.
      Despite a small number of repeated events, SAEM with three chains and AGQ gave
      small biases and RRMSE. Type I errors were closed to 5%, and power varied as
      expected for SAEM with three chains and AGQ. Probability of having at least one
      event under treatment was 19.1%. 

PMID- 24570339
TI  - Multiscale tumor spatiokinetic model for intraperitoneal therapy.
AB  - This study established a multiscale computational model for intraperitoneal (IP)
      chemotherapy, to depict the time-dependent and spatial-dependent drug
      concentrations in peritoneal tumors as functions of drug properties (size,
      binding, diffusivity, permeability), transport mechanisms (diffusion,
      convection), spatial-dependent tumor heterogeneities (vessel density, cell
      density, pressure gradient), and physiological properties (peritoneal pressure,
      peritoneal fluid volume). Equations linked drug transport and clearance on three
      scales (tumor, IP cavity, whole organism). Paclitaxel was the test compound. The
      required model parameters (tumor diffusivity, tumor hydraulic conductivity,
      vessel permeability and surface area, microvascular hydrostatic pressure, drug
      association with cells) were obtained from literature reports, calculation,
      and/or experimental measurements. Drug concentration-time profiles in peritoneal
      fluid and plasma were the boundary conditions for tumor domain and blood vessels,
      respectively. The finite element method was used to numerically solve the
      nonlinear partial differential equations for fluid and solute transport. The
      resulting multiscale model accounted for intratumoral spatial heterogeneity,
      depicted diffusive and convective drug transport in tumor interstitium and across
      blood vessels, and provided drug flux and concentration as a function of time and
      spatial position in the tumor. Comparison of model-predicted tumor spatiokinetics
      with experimental results (autoradiographic data of 3H-paclitaxel in IP ovarian
      tumors in mice, 6 h posttreatment) showed good agreement (1% deviation for area
      under curve and 23% deviations for individual data points, which were several
      fold lower compared to the experimental intertumor variations). The computational
      multiscale model provides a tool to quantify the effects of drug-, tumor-, and
      host-dependent variables on the concentrations and residence time of IP
      therapeutics in tumors.

PMID- 24570341
TI  - Analyzing subvisible particles in protein drug products: a comparison of dynamic
      light scattering (DLS) and resonant mass measurement (RMM).
AB  - Aggregation is common in protein drug manufacture, and while the effects of
      protein particulates are under investigation, many techniques applicable for
      their characterization have been recently developed. Among the methods available
      to characterize and quantify protein aggregates, none is applicable over the full
      size range and different methods often give conflicting results. The studies
      presented here compare two such methods: dynamic light scattering (DLS) and
      resonant mass measurement (RMM). The performance of each method was first
      characterized using polystyrene particle size standards (20, 60, 100, 200, 400,
      and 1,000 nm) over a range of concentrations. Standard particles were measured
      both singly and in binary mixtures containing 20 nm particles at a fixed
      concentration (10(14) particles/mL) and various concentrations of one of the
      other particle sizes (i.e., 60, 100, 200, 400, or 1,000 nm). DLS and RMM were
      then used to detect unknown aggregate content in stressed samples of IgG. Both
      instruments were shown to have a working range that depends on particle size and
      concentration. In binary mixtures and polydisperse solutions, DLS was able to
      resolve two species in a manner dependent on both concentration and particle
      size. RMM was able to resolve particles above 200 nm (150 nm for protein) at
      concentrations below 10(9) particles/mL. In addition, dilution was evaluated as a
      technique to confirm and quantify the number of particles in solution.

PMID- 24570342
TI  - Long-term low-dose exposure of human urothelial cells to sodium arsenite
      activates lipocalin-2 via promoter hypomethylation.
AB  - We previously reported that the sustained exposure of human urothelial cells
      (HUCs) to low-dose sodium arsenite induces changes in the gene expression profile
      and neoplastic transformation. In this study, we used the HumanMethylation27
      BeadChip to analyze genome-wide methylation profiles and 5-aza-2'-deoxycytidine
      to examine the involvement of promoter methylation in gene expression. Because
      the expression of lipocalin-2 (LCN2) was highly enhanced by promoter
      hypomethylation in inorganic arsenic (iAs)-HUCs cells as well as bladder cancer
      tissues, we further showed that mutations at the binding sequences for NF-kappaB
      and C/EBP-alpha significantly reduced LCN2 promoter activity. By chromatin
      immunoprecipitation assay, we demonstrated the significantly increased binding of
      RelA (p65) and NF-kappaB1 (p50) to the hypomethylated promoter of LCN2 in the iAs
      HUCs. Furthermore, we also demonstrated that LCN2 overexpression was crucial for
      the neoplastic characteristics of the iAs-HUCs, such as enhanced anchorage
      independent growth, resistance to serum deprivation and activation of NF-kappaB
      signaling. In addition, our results indicated that enhanced NF-kappaB activity in
      iAs-HUCs was via LCN2-mediated increase in intracellular iron and reactive oxygen
      species levels. Taken together, our results show that sustained low-dose arsenic
      exposure results in epigenetic changes and enhanced oncogenic potential via LCN2
      overexpression. 

PMID- 24570343
TI  - The epidemiology and aetiology of infections in children admitted with clinical
      severe pneumonia to a university hospital in Rabat, Morocco.
AB  - OBJECTIVES: Scarce and limited epidemiological, clinical and microbiological data
      are available regarding paediatric respiratory tract infections in the Kingdom of
      Morocco, a middle-income country in northwestern Africa. The results of hospital
      based surveillance aiming at describing the aetiology and epidemiology of
      respiratory distress among children <5 years of age are presented. METHODS:
      Children admitted to the Hopital d'Enfants de Rabat, Morocco, and meeting the
      World Health Organization clinical criteria for severe pneumonia were recruited
      over a period of 14 months and were thoroughly investigated to ascertain a
      definitive diagnosis. RESULTS: In total, 700 children were recruited for the
      study. Most frequent clinical diagnoses included wheezing-related conditions
      (bronchitis/asthma, 46%; bronchiolitis, 15%), while typical bacterial pneumonia
      was infrequent (only 19% of the cases). Invasive bacterial disease detected by
      classical microbiology or molecular methods was also uncommon, affecting only
      3.5% of the patients, and with an overall low detection of pneumococcal or
      Haemophilus influenzae type b disease. Conversely, coverage of respiratory viral
      detection in the nasopharynx was almost universal among cases (92%), with the
      three most frequent viruses detected being rhinovirus (53%), respiratory
      syncytial virus (18%) and adenovirus (17%). The overall case fatality rate (CFR)
      among recruited patients with a known outcome was 4.1% (28/690). CONCLUSIONS: In
      Morocco, the epidemiological profile of paediatric acute respiratory infections
      is markedly shifted towards wheezing-related diseases and thus resembles that of
      high-income countries. However, the high associated CFRs found in this study call
      for an improvement in preventive and clinical management strategies.

PMID- 24570344
TI  - Immuno-histochemistry and three-dimensional architecture of the intermediate
      filaments in Purkinje cells in mammalian hearts.
AB  - In mammalian hearts, Purkinje cells varied greatly in morphological appearance in
      different species, and were divided into three groups. Bovine Purkinje cells
      corresponding to group I were a large size, and had a few myofibrils and abundant
      intermediate filaments throughout the cytoplasm. The aim of the present study was
      to clarify the more detailed distribution and three-dimensional architecture of
      intermediate filaments in Purkinje cells. The hearts in various mammals including
      humans were investigated by both immuno-histochemistry and scanning electron
      microscopy (SEM).Immuno-histochemical studies demonstrated that sheep Purkinje
      cells in group I had a great number of intermediate filaments of 10 nm positive
      for desmin antibody. Purkinje cells in group II (humans, monkeys and dogs) and
      group III (mice) were somewhat larger or smaller in size than myocardial cells,
      but also showed a strong positive reaction for desmin antibody. The saponin or
      NaOH treatment of cardiac tissues in sheep and humans enabled us to view
      intermediate filaments by SEM three-dimensionally. Intermediate filaments in
      sheep Purkinje cells formed a considerably delicate network, and were distributed
      throughout the cytoplasm. In contrast, those in human Purkinje cells were lower
      in density, and were present around the nucleus and between myofibrils. It was
      concluded that a delicate network of intermediate filaments in Purkinje cells of
      mammalian hearts acted as the cytoskeleton to maintain intercellular stability.

PMID- 24570345
TI  - Supraretinacular endoscopic carpal tunnel release: surgical technique with
      prospective case series.
AB  - Current techniques for endoscopic carpal tunnel release use an infraretinacular
      approach, inserting the endoscope deep to the flexor retinaculum. We present a
      supraretinacular endoscopic carpal tunnel release technique in which a dissecting
      endoscope is inserted superficial to the flexor retinaculum, which improves
      vision and the ability to dissect and manipulate the median nerve and tendons
      during surgery. The motor branch of the median nerve and connections between the
      median and ulnar nerve can be identified and dissected. Because the endoscope is
      inserted superficial to the flexor retinaculum, the median nerve is not
      compressed before division of the retinaculum and, as a result, we have observed
      no cases of the transient median nerve deficits that have been reported using
      infraretinacular endoscopic techniques.

PMID- 24570346
TI  - Avascular necrosis of the capitate: report of six cases and review of the
      literature.
AB  - Avascular necrosis of the capitate is rare. Little is known about the aetiology,
      disease progression or optimal management. From 1992 to 2012 we treated six
      patients; four had a scaphocapitolunate arthrodesis and two had a four corner
      arthrodesis. The average follow up was 9 years (range 1-20). Three patients had
      good or excellent results, two fair and one poor, based on a visual analogue
      scale for pain and satisfaction and a Quick-DASH score. The Mayo wrist score was
      satisfactory in five cases and poor in one. Better results were seen when the
      arthrodesis fused. In the English, French and German literature 42 other cases
      were found. The aetiology, patient characteristics, clinical presentation,
      treatment and outcome were reviewed.

PMID- 24570348
TI  - Implications of the spatial dynamics of fire spread for the bistability of
      savanna and forest.
AB  - The role of fire in expanding the global distribution of savanna is well
      recognized. Empirical observations and modeling suggest that fire spread has a
      threshold response to fuel-layer continuity, which sets up a positive feedback
      that maintains savanna-forest bistability. However, modeling has so far failed to
      examine fire spread as a spatial process that interacts with vegetation. Here, we
      use simple, well-supported assumptions about fire spread as an infection process
      and its effects on trees to ask whether spatial dynamics qualitatively change the
      potential for savanna-forest bistability. We show that the spatial effects of
      fire spread are the fundamental reason that bistability is possible: because fire
      spread is an infection process, it exhibits a threshold response to fuel
      continuity followed by a rapid increase in fire size. Other ecological processes
      affecting fire spread may also contribute including temporal variability in
      demography or fire spread. Finally, including the potential for spatial
      aggregation increases the potential both for savanna-forest bistability and for
      savanna and forest to coexist in a landscape mosaic. 

PMID- 24570347
TI  - Characterisation of the green turtle's leukocyte subpopulations by flow cytometry
      and evaluation of their phagocytic activity.
AB  - Phagocytosis is a fundamental aspect of innate immunity that is conserved across
      many species making it a potentially useful health-assessment tool for wildlife.
      In non-mammalian vertebrates, heterophils, monocytes, macrophages,
      melanomacrophages, and thrombocytes all have phagocytic properties. Recently, B
      lymphocytes from fish, amphibians, and aquatic turtles have also showed
      phagocytic capacity. Phagocytes can be studied by flow cytometry; however, the
      use of this tool is complicated in reptiles partly because nucleated erythrocytes
      complicate the procedure. We separated green turtle leukocytes by density
      gradient centrifugation and identified subpopulations by flow cytometry and
      confocal microscopy. Additionally, we assessed their ability to phagocytize
      Fluorspheres and Ovoalbumin-Alexa. We found that heterophils and lymphocytes but
      not monocytes could be easily identified by flow cytometry. While heterophils
      from adults and juvenile turtles were equally able to phagocytize fluorspheres,
      adults had significantly more phagocytic ability for OVA-Alexa. Lymphocytes had a
      mild phagocytic activity with fluorospheres (27-38 %; 39-45 %) and OVA-Alexa (35
      46 %; 14-22 %) in juvenile and adult green turtles, respectively. Confocal
      microscopy confirmed phagocytosis of fluorospheres in both heterophils and
      lymphocytes. This provides the first evidence that green turtle lymphocytes have
      phagocytic activity and that this assay could potentially be useful to measure
      one aspect of innate immunity in this species. 

PMID- 24570350
TI  - An ideal-observer model of human sound localization.
AB  - In recent years, a great deal of research within the field of sound localization
      has been aimed at finding the acoustic cues that human listeners use to localize
      sounds and understanding the mechanisms by which they process these cues. In this
      paper, we propose a complementary approach by constructing an ideal-observer
      model, by which we mean a model that performs optimal information processing
      within a Bayesian context. The model considers all available spatial information
      contained within the acoustic signals encoded by each ear. Parameters for the
      optimal Bayesian model are determined based on psychoacoustic discrimination
      experiments on interaural time difference and sound intensity. Without regard as
      to how the human auditory system actually processes information, we examine the
      best possible localization performance that could be achieved based only on
      analysis of the input information, given the constraints of the normal auditory
      system. We show that the model performance is generally in good agreement with
      the actual human localization performance, as assessed in a meta-analysis of many
      localization experiments (Best et al. in Principles and applications of spatial
      hearing, pp 14-23. World Scientific Publishing, Singapore, 2011). We believe this
      approach can shed new light on the optimality (or otherwise) of human sound
      localization, especially with regard to the level of uncertainty in the input
      information. Moreover, the proposed model allows one to study the relative
      importance of various (combinations of) acoustic cues for spatial localization
      and enables a prediction of which cues are most informative and therefore likely
      to be used by humans in various circumstances. 

PMID- 24570349
TI  - Synthesis and characterization of zinc and calcium nanoferrites.
AB  - In this work, Zn(1-x)CaxFe(2)O(4) nanoparticles (x = 0, 0.5 and 1) have been
      synthesized by sol-gel method followed by heat treatment at a temperature within
      the range of 300-700  degrees C. The samples with appropriate saturation
      magnetization (Ms), low coercivity and remanence were Zn(0)Ca(1)Fe(2)O(4) treated
      at 300  degrees C (Ms ~ 25 emu/g), Zn(0)Ca(1)Fe(2)O(4) treated at 400  degrees C
      (Ms ~ 40 emu/g) and Zn(0.50)Ca(0.50)Fe(2)O(4) treated at 400  degrees C (Ms ~ 31
      emu/g). These samples were analyzed by scanning electron microscopy, energy
      dispersive spectroscopy, X-ray diffraction and transmission electron microscopy.
      The heating ability of selected nanoparticles was evaluated under a magnetic
      field using a solid state induction heating equipment. The obtained nanoferrites
      showed a particle size within the range of 13-14 nm. The Zn(0)Ca(1)Fe(2)O(4)
      treated at 400  degrees C was able to heat the nanoferrite particles/water
      suspension (10 mg/2 ml) at a temperature of 44  degrees C under the selected
      magnetic field (10.2 kA/m and frequency 362 kHz). Additionally, in vitro
      bioactivity assessment was performed by immersing samples in a simulated body
      fluid for different periods of time at physiological conditions of pH and
      temperature. The samples showed an appropriate bioactivity. These nanoferrites
      are highly potential materials for hyperthermia treatment.

PMID- 24570351
TI  - A computational model of the effect of gene misexpression on the development of
      cortical areas.
AB  - Brain function depends on the specialisation of brain areas. In the murine
      cerebral cortex, the development of these areas depends on the coordinated
      expression of several genes in precise spatial patterns in the telencephalon
      during embryogenesis. Manipulating the expression of these genes during
      development alters the positions and sizes of cortical areas in the adult.
      Qualitative data also show that these genes regulate each other's expression
      during development so that they form a regulatory network with many feedback
      loops. However, it is currently unknown which regulatory interactions are
      critical to generating the correct expression patterns to lead to normal cortical
      development. Here, we formalise the relationships inferred from genetic
      manipulations into computational models. We simulate many different networks
      potentially consistent with the experimental data and show that a surprising
      diversity of networks produce similar results. This demonstrates that existing
      data cannot uniquely specify the network. We conclude by suggesting experiments
      necessary to constrain the model and help identify and understand the true
      structure of this regulatory network. 

PMID- 24570352
TI  - Learning robotic eye-arm-hand coordination from human demonstration: a coupled
      dynamical systems approach.
AB  - We investigate the role of obstacle avoidance in visually guided reaching and
      grasping movements. We report on a human study in which subjects performed
      prehensile motion with obstacle avoidance where the position of the obstacle was
      systematically varied across trials. These experiments suggest that reaching with
      obstacle avoidance is organized in a sequential manner, where the obstacle acts
      as an intermediary target. Furthermore, we demonstrate that the notion of
      workspace travelled by the hand is embedded explicitly in a forward planning
      scheme, which is actively involved in detecting obstacles on the way when
      performing reaching. We find that the gaze proactively coordinates the pattern of
      eye-arm motion during obstacle avoidance. This study provides also a quantitative
      assessment of the coupling between the eye-arm-hand motion. We show that the
      coupling follows regular phase dependencies and is unaltered during obstacle
      avoidance. These observations provide a basis for the design of a computational
      model. Our controller extends the coupled dynamical systems framework and
      provides fast and synchronous control of the eyes, the arm and the hand within a
      single and compact framework, mimicking similar control system found in humans.
      We validate our model for visuomotor control of a humanoid robot. 

PMID- 24570353
TI  - Multi-layered multi-pattern CPG for adaptive locomotion of humanoid robots.
AB  - In this paper, we present an extended mathematical model of the central pattern
      generator (CPG) in the spinal cord. The proposed CPG model is used as the
      underlying low-level controller of a humanoid robot to generate various walking
      patterns. Such biological mechanisms have been demonstrated to be robust in
      locomotion of animal. Our model is supported by two neurophysiological studies.
      The first study identified a neural circuitry consisting of a two-layered CPG, in
      which pattern formation and rhythm generation are produced at different levels.
      The second study focused on a specific neural model that can generate different
      patterns, including oscillation. This neural model was employed in the pattern
      generation layer of our CPG, which enables it to produce different motion
      patterns-rhythmic as well as non-rhythmic motions. Due to the pattern-formation
      layer, the CPG is able to produce behaviors related to the dominating rhythm
      (extension/flexion) and rhythm deletion without rhythm resetting. The proposed
      multi-layered multi-pattern CPG model (MLMP-CPG) has been deployed in a 3D
      humanoid robot (NAO) while it performs locomotion tasks. The effectiveness of our
      model is demonstrated in simulations and through experimental results. 

PMID- 24570354
TI  - Bioregenerative medicine.

PMID- 24570356
TI  - In silico analysis on structure and DNA binding mode of AtNAC1, a NAC
      transcription factor from Arabidopsis thaliana.
AB  - NAC (NAM/ATAF/CUC) transcription factors regulate the expression of the target
      genes by formation of NAC-DNA complex, which are involved in development, stress
      responses and nutrient distribution in many metaphyta plants. AtNAC1, a NAC
      transcription factor from Arabidopsis thaliana, plays an important role in auxin
      signaling and root development. In order to understand the structure and DNA
      binding model of AtNAC1, the 3D structure model of AtNAC1 was constructed and
      docked with its target DNA. The structure of AtNAC1 monomer contained four alpha
      helices and eight beta-sheets. Two homo monomers of AtNAC1 formed a homo-dimer.
      The N-terminal sheet S1, Arg24 and Glu31 played an important role in forming
      AtNAC1 homo-dimer. AtNAC1 dimer interacted with DNA via its core beta-sheet (S5)
      which contained WKATGKD motif inserting into the major groove of DNA and formed a
      tight AtNAC1-DNA complex. The DNA sites for AtNAC1 binding were 5'-CTGACGTA-3'
      and 5'-GATGACGC-3'. Lys102, Ala103, Thr104, Gly105, Lys106, and Asp107
      interacting with sugars/bases of DNA were probably responsible for specific
      recognition of DNA sites. Meanwhile, Arg91, Lys135, and Lys171 binding with
      phosphate groups of DNA backbone might be the key residues for affinity with DNA.
      The study provided the in silico framework to understand the interactions of
      AtNAC1 with DNA at the molecular level. 

PMID- 24570355
TI  - Duodenal-jejunal bypass liner to treat type 2 diabetes mellitus in morbidly obese
      patients.
AB  - Endoscopic placement of the duodenal-jejunal bypass liner (DJBL) in morbidly
      obese patients induces significant weight loss. Additionally, early studies
      reported significant improvements in several parameters of glucose homeostasis in
      morbidly obese patients with T2DM. The observed glycemic control occurred soon
      after device placement, after a minimal weight loss, suggesting the activation of
      weight loss-independent anti-diabetic mechanisms of glucose normalization. This
      effect is associated with favorable changes in hormones involved in glucose level
      regulation. Recently, larger clinical studies, focused primarily on the effect of
      the DJBL on T2DM treatment, have corroborated initial observations not only in
      morbidly obese patients but in non-morbidly obese diabetic patients as well. In
      this article we review the evidence from preclinical animal and clinical human
      studies that support the efficacy of DJBL to treat T2DM in obese patients.

PMID- 24570357
TI  - [Iatrogenic after spinal puncture technique. Prevalence study of headache and
      associated factors].
AB  - AIM: To determine the prevalence of headache following a transdural lumbar
      puncture and the risk factors involved. PATIENTS AND METHODS: The method used was
      a prospective observation-based cohort study. Patients were recruited from the A
      and E Department, Neurology Service and Day Care Clinic. The following data were
      collected: physician's experience, number of punctures, variations in the plane,
      patient's posture, local anaesthetic, needle calibre and bevel, degrees of
      inclination, amount of liquid, fluid overload and whether or not rest is
      indicated after the puncture. After 48 hours, the appearance of headache (or not)
      was determined. RESULTS: The sample consisted of 59 patients, 31 (52.5%) of whom
      were males. Mean age: 47 years; 32 patients (54.2%) came from A and E, 18 (30.5%)
      from Neurology and 9 (15.3%) from the Day Care Clinic. Forty-one (69.5%) received
      the lumbar puncture in a lateral decubitus position and 7 (11.9%) in a seated
      position. All the needles were bevelled, 21 (35.6%) with a calibre of 20 and 38
      (64.4%) of calibre 22. Eight patients (13.56%) were without repose and 18 (33.3%)
      had no fluid overload. Twenty-three (38.98%) had post-lumbar-puncture headache,
      12 (52.2%) of them females, with a mean age of 38.3 +/- 16.4 years. The median of
      the headache intensity was 2.6. The mean time of appearance was seven hours.
      There were no differences for any of the factors studied, except the observed
      tendency towards a higher incidence of headache at younger ages. CONCLUSIONS:
      Rates of post-lumbar-puncture headache in our series are high, and no differences
      were found in terms of the service where it was performed or experience. No
      influence was observed due to the amount of liquid extracted, the patient's
      position, the indication of repose or fluid overload.

PMID- 24570358
TI  - [Erythropoietin as a protective factor in rat CNS cells receiving radiotherapy 
      an in vitro study].
AB  - AIM: To investigate the effect of erythropoietin in cultured rat cerebral cortex
      cells receiving radiotherapy. MATERIALS AND METHODS: Cerebral cortex was taken
      from 17-day-old Wistar rat embryos and placed in culture. At 72 hours, the
      cultures were divided into two groups, one receiving 30 pM erythropoietin alpha
      and the other was the control group. Both groups received 6 Gy from a Phoenix
      apparatus and were incubated for another 24 hours before fixation in 4%
      formaldehyde. TUNEL technique was employed to calculate the number of apoptotic
      cells in the irradiated cultures. RESULTS: Apoptosis affected 25.22% of the cells
      cultured without erythropoietin and 15.5% in the group receiving erithropoyetin.
      Student's t-test was used to analyse quantitative variables and showed a
      significant difference in apoptosis between the two groups (p < 0.0001).
      CONCLUSION: Our in vitro experimental model demonstrated that erythropoietin
      effectively prevents apoptosis in irradiated rat SNC cells, opening new fields
      for investigation into protective agents for the nervous system.

PMID- 24570359
TI  - [Musical hallucinations: perpetual music].
AB  - INTRODUCTION: Musical hallucinations are a kind of auditory hallucination that
      are prevalent among the non-psychiatric population, but which have rarely been
      reported in the neurological literature. They occur most frequently in the
      elderly, in females and when there is a loss of hearing, but their
      pathophysiology has still to be unravelled. CASE REPORTS: We report here six
      cases (five females and one male) of musical hallucinations diagnosed in a
      general neurology clinic over a time-span of five years. In five cases there was
      also concurrent hypoacusis, to a greater or lesser extent, and one had been
      triggered by pentoxifylline. In most instances, the musical content of the
      hallucinations had its origins in music experienced in childhood and early youth.
      In the cases submitted to pharmacological treatment, the response was poor. Yet,
      after explaining to the patients that the condition was benign and had no
      connection with a psychotic pathology, the degree of acceptance of the symptoms
      was good. CONCLUSIONS: Musical hallucinations are a little-known pathology lying
      on the borderline between neurology, otorhinolaryngology and psychiatry which are
      often wrongly linked to mental disease. It is essential to explain to patients
      and relatives that these symptoms are not necessarily of a psychiatric nature,
      and to be aware of the potential capacity of some commonly used drugs to generate
      them.

PMID- 24570360
TI  - [Neurological disorders and the blood-brain barrier. Strategies and limitations
      for drug delivery to the brain].
AB  - INTRODUCTION: The incidence in the central nervous system diseases has increased
      with a growing elderly population. Unfortunately, conventional treatments used to
      treat the mentioned diseases are frequently ineffective due to the presence of
      the blood brain barrier. AIM: To illustrate the blood-brain barrier properties
      that limit drug transport into the brain and the main strategies employed to
      treat neurologic disorders. DEVELOPMENT: The blood-brain barrier is mainly
      composed of a specialized microvascular endothelium and of glial cells. It
      constitutes a valuable tool to separate the central nervous system from the rest
      of the body. Nevertheless, it also represents an obstacle to the delivery of
      therapeutic drugs to the brain. CONCLUSIONS: To be effective, drugs must reach
      their target in the brain. On one hand, therapeutic agents could be designed to
      be able to cross the blood brain barrier. On the other hand, drug delivery
      systems could be employed to facilitate the therapeutic agents' entry into the
      central nervous system. In vivo models of neurological diseases, in addition to
      in vitro models of the blood brain barrier, have been widely employed for the
      evaluation of drugs utilized to treat central nervous system diseases.

PMID- 24570361
TI  - [Neuroethics (I): moral pathways in normal brain].
AB  - INTRODUCTION: Morality is made of rules and values that guide human behavior.
      They barely change among different cultures. Social accomplishments are the
      result of moral development, due to a taint of fairness which pervades any human
      activity. The moral functions are the consequence of evolution and have their own
      specific neural circuits. AIM: To describe their appearance, starting and
      underlying mechanisms in the normal brain. DEVELOPMENT: Moral responses are
      basically homogeneous. They are linked to the emotional development, as much
      basic and individual (fear, wrath) as social (compassion, justice). Their
      emergence is the result of the emotional dichotomies pleasure/pain and
      reward/punishment, which lead to the basic moral dichotomy good/bad. For their
      working it is required the running of the prefrontal cortex (ventromedian and
      dorsolateral), the anterior cingular cortex and the superior temporal sulcus,
      that asses and elaborate and utilitarian moral response; and also the insula, the
      amygdale and the hypothalamus, that perform a quicker and emotionally rooted
      response. In addition, the mirror neuronal system (fronto-parietal) enables motor
      learning and empathy, linking this factor to the theory of mind. CONCLUSIONS:
      Moral sense and its responses underlay the complex social development that humans
      have reached and enjoyed. Thus opens ways for improving benefits in human groups
      and individuals alike. In addition, the knowledge of the normal function of the
      moral circuits is permeating and influencing the many areas of neuroculture.

PMID- 24570363
TI  - [Blepharospasm as the presenting symptom of a brain stem glioma].

PMID- 24570362
TI  - [The 'black turbinate sign' in a case of rhinocerebral mucormycosis].

PMID- 24570364
TI  - [Bilateral thalamic ischaemia secondary to a tentorial dural fistula].

PMID- 24570365
TI  - [Etanercept: does it constitute a risk factor for development of cerebral venous
      thrombosis?].

PMID- 24570366
TI  - Acetic Acid, the active component of vinegar, is an effective tuberculocidal
      disinfectant.
AB  - Effective and economical mycobactericidal disinfectants are needed to kill both
      Mycobacterium tuberculosis and non-M. tuberculosis mycobacteria. We found that
      acetic acid (vinegar) efficiently kills M. tuberculosis after 30 min of exposure
      to a 6% acetic acid solution. The activity is not due to pH alone, and propionic
      acid also appears to be bactericidal. M. bolletii and M. massiliense
      nontuberculous mycobacteria were more resistant, although a 30-min exposure to
      10% acetic acid resulted in at least a 6-log10 reduction of viable bacteria.
      Acetic acid (vinegar) is an effective mycobactericidal disinfectant that should
      also be active against most other bacteria. These findings are consistent with
      and extend the results of studies performed in the early and mid-20th century on
      the disinfectant capacity of organic acids. IMPORTANCE Mycobacteria are best
      known for causing tuberculosis and leprosy, but infections with nontuberculous
      mycobacteria are an increasing problem after surgical or cosmetic procedures or
      in the lungs of cystic fibrosis and immunosuppressed patients. Killing
      mycobacteria is important because Mycobacterium tuberculosis strains can be
      multidrug resistant and therefore potentially fatal biohazards, and environmental
      mycobacteria must be thoroughly eliminated from surgical implements and
      respiratory equipment. Currently used mycobactericidal disinfectants can be
      toxic, unstable, and expensive. We fortuitously found that acetic acid kills
      mycobacteria and then showed that it is an effective mycobactericidal agent, even
      against the very resistant, clinically important Mycobacterium abscessus complex.
      Vinegar has been used for thousands of years as a common disinfectant, and if it
      can kill mycobacteria, the most disinfectant-resistant bacteria, it may prove to
      be a broadly effective, economical biocide with potential usefulness in health
      care settings and laboratories, especially in resource-poor countries.

PMID- 24570367
TI  - Generation of unique poliovirus RNA replication organelles.
AB  - Poliovirus (PV), a model for interactions of picornaviruses with host cells,
      replicates its genomic RNA in association with cellular membranes. The origin of
      PV replication membranes has not been determined. Hypotheses about the origin of
      replication membranes, based largely on localization of viral proteins, include
      modification of coat protein complex I (COPI) and/or COPII secretory pathway
      vesicles and subversion of autophagic membranes. Here, we use an antibody against
      double-stranded RNA (dsRNA) to identify replication complexes by detection of
      dsRNA replication intermediates. dsRNA signal is dependent on virus genome
      replication and colocalizes with the viral integral membrane protein 3A, which is
      part of the RNA replication complex. We show that early in infection, dsRNA does
      not colocalize with a marker for autophagic vesicles, making it unlikely that
      autophagosomes contribute to the generation of PV RNA replication membranes. We
      also find that dsRNA does not colocalize with a marker of the COPII coat, Sec31,
      and, in fact, we demonstrate proteasome-dependent loss of full-length Sec31
      during PV infection. These data indicate that COPII vesicles are an unlikely
      source of PV replication membranes. We show that the Golgi resident G-protein
      Arf1 and its associated guanine nucleotide exchange factor (GEF), GBF1,
      transiently colocalize with dsRNA early in infection. In uninfected cells, Arf1
      nucleates COPI coat formation, although during infection the COPI coat itself
      does not colocalize with dsRNA. Phosphatidylinositol-4-phosphate, which is
      associated with enterovirus-induced vesicles, tightly colocalizes with Arf1/GBF1
      throughout infection. Our data point to a noncanonical role for some of the COPI
      generating machinery in producing unique replication surfaces for PV RNA
      replication. IMPORTANCE Picornaviruses are a diverse and major cause of human
      disease, and their genomes replicate in association with intracellular membranes.
      There are multiple hypotheses to explain the nature and origin of these
      membranes, and a complete understanding of the host requirements for membrane
      rearrangement would provide novel drug targets essential for viral genome
      replication. Here, we study the model picornavirus, poliovirus, and show that
      some, but not all, components of the cellular machinery required for retrograde
      traffic from the Golgi apparatus to the endoplasmic reticulum are transiently
      present at the sites of viral RNA replication. We also show that the full-length
      Sec31 protein, which has been suggested to be present on PV RNA replication
      membranes, is lost during infection in a proteasome-dependent manner. This study
      helps to reconcile multiple hypotheses about the origin of poliovirus replication
      membranes and points to known host cell protein complexes that would make likely
      drug targets to inhibit picornavirus infections.

PMID- 24570368
TI  - Cell-type-specific effects of RNase L on viral induction of beta interferon.
AB  - The interferon (IFN)-inducible antiviral state is mediated in part by the 2',5'
      oligoadenylate (2-5A) synthetase (OAS)/RNase L system. 2-5A, produced from ATP by
      OAS proteins in response to viral double-stranded RNA, binds to and activates
      RNase L. RNase L restricts viral infections by degrading viral and cellular RNA,
      inducing autophagy and apoptosis, and producing RNA degradation products that
      amplify production of type I interferons (IFNs) through RIG-I-like receptors.
      However, the effects of the OAS/RNase L pathway on IFN induction in different
      cell types that vary in basal levels of these proteins have not been previously
      reported. Here we report higher basal expression of both RNase L and OAS in mouse
      macrophages in comparison to mouse embryonic fibroblasts (MEFs). In MEFs, RNase L
      gene knockout decreased induction of IFN-beta by encephalomyocarditis virus
      infection or poly(rI):poly(rC) (pIC) transfection. In contrast, in macrophages,
      RNase L deletion increased (rather than decreased) induction of IFN-beta by virus
      or pIC. RNA damage from RNase L in virus-infected macrophages is likely
      responsible for reducing IFN-beta production. Similarly, direct activation of
      RNase L by transfection with 2-5A induced IFN-beta in MEFs but not in
      macrophages. Also, viral infection or pIC transfection caused RNase L-dependent
      apoptosis of macrophages but not of MEFs. Our results suggest that cell-type
      specific differences in basal levels of OAS and RNase L are determinants of IFN
      beta induction that could affect tissue protection and survival during viral
      infections. IMPORTANCE Type I interferons (IFNs) such as IFN-beta are essential
      antiviral cytokines that are often required for animal survival following
      infections by highly pathogenic viruses. Therefore, host factors that regulate
      type I IFN production are critically important for animal and human health.
      Previously we reported that the OAS/RNase L pathway amplifies antiviral innate
      immunity by enhancing IFN-beta production in mouse embryonic fibroblasts and in
      virus-infected mice. Here we report that high basal levels of OAS/RNase L in
      macrophages reduce, rather than increase, virus induction of IFN-beta. RNA damage
      and apoptosis caused by RNase L were the likely reasons for the decreased IFN
      beta production in virus-infected macrophages. Our studies suggest that during
      viral infections, the OAS/RNase L pathway can either enhance or suppress IFN
      production, depending on the cell type. IFN regulation by RNase L is suggested to
      contribute to tissue protection and survival during viral infections.

PMID- 24570369
TI  - Honey bee-infecting plant virus with implications on honey bee colony health.
AB  - Honey bees are eusocial insects that are commercially managed to provide
      pollination services for agricultural crops. Recent increased losses of honey bee
      colonies (averaging 32% annually since 2006) are associated with the incidence
      and abundance of pathogens. In their study in mBio, J. L. Li et al. [mBio
      5(1):e00898-13, 2014, doi:10.1128/mBio.00898-13] share their discovery that a
      plant virus, tobacco ring spot virus (TRSV), replicates in honey bees and that
      the prevalence of this virus was high in weak colonies. Their findings increase
      our understanding of the role of viruses in honey bee colony losses and
      underscore the importance of surveying for new and/or emerging viruses in honey
      bees. Furthermore, their findings will pique the interest of virologists and
      biologists across all disciplines. The discovery that a plant virus (TRSV)
      replicates, spreads, and negatively affects the health of an insect host will
      lead to additional studies on the mechanisms of host-specific adaptation and the
      role of cross-kingdom infections in the transmission of this virus.

PMID- 24570370
TI  - Middle East respiratory syndrome coronavirus infection in dromedary camels in
      Saudi Arabia.
AB  - The Middle East respiratory syndrome (MERS) is proposed to be a zoonotic disease;
      however, the reservoir and mechanism for transmission of the causative agent, the
      MERS coronavirus, are unknown. Dromedary camels have been implicated through
      reports that some victims have been exposed to camels, camels in areas where the
      disease has emerged have antibodies to the virus, and viral sequences have been
      recovered from camels in association with outbreaks of the disease among humans.
      Nonetheless, whether camels mediate transmission to humans is unresolved. Here we
      provide evidence from a geographic and temporal survey of camels in the Kingdom
      of Saudi Arabia that MERS coronaviruses have been circulating in camels since at
      least 1992, are distributed countrywide, and can be phylogenetically classified
      into clades that correlate with outbreaks of the disease among humans. We found
      no evidence of infection in domestic sheep or domestic goats. IMPORTANCE This
      study was undertaken to determine the historical and current prevalence of Middle
      East respiratory syndrome (MERS) coronavirus infection in dromedary camels and
      other livestock in the Kingdom of Saudi Arabia, where the index case and the
      majority of cases of MERS have been reported.

PMID- 24570372
TI  - Inhibitors of TonB function identified by a high-throughput screen for inhibitors
      of iron acquisition in uropathogenic Escherichia coli CFT073.
AB  - The urinary tract is one of the most common sites of infection in humans, and
      uropathogenic Escherichia coli (UPEC) is the main causative agent of urinary
      tract infections. Bacteria colonizing the urinary tract face extremely low iron
      availability. To counteract this, UPEC expresses a wide variety of iron
      acquisition systems. To exploit iron acquisition in UPEC as a global target for
      small-molecule inhibition, we developed and carried out a whole-cell growth-based
      high throughput screen of 149,243 compounds. Our primary assay was carried out
      under iron-limiting conditions. Hits in the primary screen were assayed using two
      counterscreens that ruled out iron chelators and compounds that inhibit growth by
      means other than inhibition of iron acquisition. We determined dose-response
      curves under two different iron conditions and purchased fresh compounds for
      selected hits. After retesting dose-response relationships, we identified 16
      compounds that arrest growth of UPEC only under iron-limiting conditions. All
      compounds are bacteriostatic and do not inhibit proton motive force. A loss-of
      target strategy was employed to identify the cellular target of these inhibitors.
      Two compounds lost inhibitory activity against a strain lacking TonB and were
      shown to inhibit irreversible adsorption of a TonB-dependent bacteriophage. Our
      results validate iron acquisition as a target for antibacterial strategies
      against UPEC and identify TonB as one of the cellular targets. IMPORTANCE Half of
      women will suffer at least one episode of urinary tract infection (UTI) during
      their lifetime. The current treatment for UTI involves antibiotic therapy.
      Resistance to currently used antibiotics has steadily increased over the last
      decade, generating a pressing need for the development of new therapeutic agents.
      Since iron is essential for colonization and scarce in the urinary tract,
      targeting iron acquisition would seem to be an attractive strategy. However, the
      multiplicity and redundancy of iron acquisition systems in uropathogenic
      Escherichia coli (UPEC) make it difficult to pinpoint a specific cellular target.
      Here, we identified 16 iron acquisition inhibitors through a whole-cell high
      throughput screen, validating iron acquisition as a target for antibacterial
      strategies against UPEC. We also identified the cellular target of two of the
      inhibitors as the TonB system.

PMID- 24570373
TI  - Recent trends in coverage of the Mexican-born population of the United States:
      results from applying multiple methods across time.
AB  - The accuracy of counts of U.S. racial/ethnic and immigrant groups depends on the
      coverage of the foreign-born in official data. Because Mexicans constitute by far
      the largest single national-origin group among the foreign-born in the United
      States, we compile new evidence about the coverage of the Mexican-born population
      in the 2000 census and 2001-2010 American Community Survey (ACS) using three
      techniques: a death registration, a birth registration, and a net migration
      method. For the late 1990s and first half of the 2000-2010 decade, results
      indicate that coverage error was somewhat higher than currently assumed but had
      substantially declined by the latter half of the 2000-2010 decade. Additionally,
      we find evidence that U.S. census and ACS data miss substantial numbers of
      children of Mexican immigrants, as well as people who are most likely to be
      unauthorized: namely, working-aged Mexican immigrants (ages 15-64), especially
      males. The findings highlight the heterogeneity of the Mexican foreign-born
      population and the ways in which migration dynamics may affect population
      coverage. 

PMID- 24570371
TI  - Single clinical isolates from acute uncomplicated urinary tract infections are
      representative of dominant in situ populations.
AB  - Urinary tract infections (UTIs) are one of the most commonly acquired bacterial
      infections in humans, and uropathogenic Escherichia coli strains are responsible
      for over 80% of all cases. The standard method for identification of uropathogens
      in clinical laboratories is cultivation, primarily using solid growth media under
      aerobic conditions, coupled with morphological and biochemical tests of typically
      a single isolate colony. However, these methods detect only culturable
      microorganisms, and characterization is phenotypic in nature. Here, we explored
      the genotypic identity of communities in acute uncomplicated UTIs from 50
      individuals by using culture-independent amplicon pyrosequencing and whole-genome
      and metagenomic shotgun sequencing. Genus-level characterization of the UTI
      communities was achieved using the 16S rRNA gene (V8 region). Overall UTI
      community richness was very low in comparison to other human microbiomes. We
      strain-typed Escherichia-dominated UTIs using amplicon pyrosequencing of the
      fimbrial adhesin gene, fimH. There were nine highly abundant fimH types, and each
      UTI sample was dominated by a single type. Molecular analysis of the
      corresponding clinical isolates revealed that in the majority of cases the
      isolate was representative of the dominant taxon in the community at both the
      genus and the strain level. Shotgun sequencing was performed on a subset of eight
      E. coli urine UTI and isolate pairs. The majority of UTI microbial metagenomic
      sequences mapped to isolate genomes, confirming the results obtained using
      phylogenetic markers. We conclude that for the majority of acute uncomplicated E.
      coli-mediated UTIs, single cultured isolates are diagnostic of the infection.
      IMPORTANCE In clinical practice, the diagnosis and treatment of acute
      uncomplicated urinary tract infection (UTI) are based on analysis of a single
      bacterial isolate cultured from urine, and it is assumed that this isolate
      represents the dominant UTI pathogen. However, these methods detect only
      culturable bacteria, and the existence of multiple pathogens as well as strain
      diversity within a single infection is not examined. Here, we explored bacteria
      present in acute uncomplicated UTIs using culture-independent sequence-based
      methods. Escherichia coli was the most common organism identified, and analysis
      of E. coli dominant UTI samples and their paired clinical isolates revealed that
      in the majority of infections the cultured isolate was representative of the
      dominant taxon at both the genus and the strain level. Our data demonstrate that
      in most cases single cultured isolates are diagnostic of UTI and are consistent
      with the notion of bottlenecks that limit strain diversity during UTI
      pathogenesis.

PMID- 24570374
TI  - Application of carrier and plasticizer to improve the dissolution and
      bioavailability of poorly water-soluble baicalein by hot melt extrusion.
AB  - The objective of this study was to develop a suitable formulation for baicalein
      (a poorly water-soluble drug exhibiting high melting point) to prepare solid
      dispersions using hot melt extrusion (HME). Proper carriers and plasticizers were
      selected by calculating the Hansen solubility parameters, evaluating melting
      processing condition, and measuring the solubility of obtained melts. The
      characteristic of solid dispersions prepared by HME was evaluated. The
      dissolution performance of the extrudates was compared to the pure drug and the
      physical mixtures. Physicochemical properties of the extrudates were
      characterized by differential scanning calorimetry (DSC), powder X-ray
      diffraction (PXRD), and Fourier transform infrared spectroscopy (FTIR). Relative
      bioavailability after oral administration in beagle dogs was assessed. As a
      result, Kollidon VA64 and Eudragit EPO were selected as two carriers; Cremophor
      RH was used as the plasticizer. The dissolution of all the extrudates was
      significantly improved. DSC and PXRD results suggested that baicalein in the
      extrudates was amorphous. FTIR spectroscopy revealed the interaction between drug
      and polymers. After oral administration, the relative bioavailability of solid
      dispersions with VA64 and EPO was comparative, about 2.4- and 2.9-fold greater
      compared to the pure drug, respectively.

PMID- 24570377
TI  - Effect of carbonylcyanide-4-(trifluoromethoxy)phenylhydrazone (FCCP) on the
      interaction of 1-anilino-8-naphthalene sulfonate (ANS) with phosphatidylcholine
      liposomes.
AB  - The weak hydrophobic acid carbonylcyanide-4-(trifluoromethoxy)phenylhydrazone
      (FCCP) is a protonophoric uncoupler of oxidative phosphorylation in mitochondria.
      It dissipates the electrochemical proton gradient (DeltaMUH (+)) increasing the
      mitochondrial oxygen consumption. However, at concentrations higher than 1 MUM it
      exhibits additional effects on mitochondrial energy metabolism, which were
      tentatively related to modifications of electrical properties of the membrane.
      Here we describe the effect of FCCP on the binding of 1-anilino-8-naphthalene
      sulfonate (ANS) to 1, 2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and 1,2
      dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) unilamellar vesicles. FCCP
      inhibited the binding of ANS to liposomes either in the gel or in the liquid
      crystalline phase, by increasing the apparent dissociation constant of ANS.
      Smaller effect on the dissociation constant was observed at high ionic strength,
      suggesting that the effect of FCCP is through modification of the electrostatic
      properties of the membrane interface. In addition, FCCP also decreased
      (approximately 50 %) the quantum yield and increased the intrinsic dissociation
      constant of membrane-bound ANS, results that suggest that FCCP makes the
      environment of the ANS binding sites more polar. On those grounds we postulate
      that the binding of FCCP: i) increases the density of negative charges in the
      membrane surface; and ii) distorts the phospholipid bilayer, increasing the
      mobility of the polar headgroups making the ANS binding site more accessible to
      water. 

PMID- 24570378
TI  - Usefulness of contrast-enhanced intraoperative ultrasound in identifying
      disappearing liver metastases from colorectal carcinoma after chemotherapy.
AB  - BACKGROUND: Preoperative chemotherapy sometimes makes colorectal liver metastases
      disappear or diminish. Contrast-enhanced intraoperative ultrasound (CE-IOUS)
      using perflubutane may identify such metastases. METHODS: Among 131 consecutive
      patients who underwent hepatic resection, 86 had received preoperative
      chemotherapy. Of these patients, 72 were examined using contrast-enhanced
      computed tomography (CE-CT), gadolinium ethoxybenzyl diethylenetriamine
      pentaacetic acid-enhanced magnetic resonance imaging (EOB-MRI), contrast-enhanced
      ultrasound (CEUS), intraoperative ultrasound (IOUS), and CE-IOUS; these patients
      were the subject of the present study. Effects of IOUS and CE-IOUS to search for
      disappearing liver metastases (DLM) and tumors with a diameter of 1 cm or less
      based on the preoperative imaging were assessed. RESULTS: A total of 32 DLMs were
      noted in 11 patients. Four DLMs were identified using IOUS, and 16 DLMs
      (including the four DLMs identified using IOUS) were identified using CE-IOUS. Of
      the 16 DLMs that were missed using both IOUS and CE-IOUS, nine were resected
      using anatomical resection and seven were not resected. One of the nine resected
      DLMs was histologically proven to be adenocarcinoma. Three of the seven
      unresected DLMs showed tumor regrowth during a postoperative follow-up
      examination. CE-IOUS identified 79 % of the 19 DLMs that were ultimately
      confirmed as liver metastases, whereas IOUS identified 21 % of them (p < 0.004).
      Among the 202 tumors that were identified using preoperative imaging, 54 were 1
      cm or less in diameter. The sensitivity of CE-IOUS for these tumors were superior
      to CE-CT (p < 0.04) and IOUS (p < 0.04), respectively. CONCLUSIONS: CE-IOUS might
      be necessary after preoperative chemotherapy for colorectal liver metastasis.

PMID- 24570379
TI  - Chemotherapy and targeted therapy for patients with initially unresectable
      colorectal liver metastases, focusing on conversion hepatectomy and long-term
      survival.
AB  - BACKGROUND: Eight years have passed since the introduction of chemotherapy
      (chemo) and targeted therapy regimens for colorectal liver metastases (CRLM).
      This study aimed to clarify the effectiveness of chemo and targeted therapy in
      facilitating conversion hepatectomy and improving long-term survival in Japanese
      patients with CRLM. METHODS: A total of 199 patients with CRLM were treated
      between May 2005 and August 2012. Initial therapies for these patients included
      straightforward hepatic resection (n = 48; 24 %), induction chemotherapy (n =
      148; 74 %), and radiofrequency ablation (n = 3; 2 %). RESULTS: In 56 of 137
      patients (40.1 %) with initially unresectable CRLM, 7.5 courses of chemo and
      targeted therapy downsized and converted tumors to resectable tumors. The 5-year
      cumulative overall survival (OS) rate and the median survival time were
      significantly higher for the resectable CRLM than for the unresectable CRLM (54.6
      vs. 5.3 % and 77.3 vs. 21.3 months, respectively; P < .0001). Multivariate
      analysis revealed that conversion hepatectomy (hazard ratio [HR] 0.19; P < .001)
      and responder to chemo and targeted therapy (HR 0.46; P < .01) were independent
      prognostic factors for OS. Multivariate analysis also revealed that left-sided
      colon or rectal cancer (odds ratio [OR] 8.4; P < .05), H1/H2 metastases (OR 7.3;
      P < .05), no extrahepatic metastases (OR 52.6; P < .001), and responder to chemo
      and targeted therapy (OR 6.1; P < .05) were significant predictors of conversion
      hepatectomy. CONCLUSIONS: A chemo and targeted therapy can facilitate conversion
      hepatectomy and allow for an excellent prognosis in patients with initially
      unresectable CRLM.

PMID- 24570381
TI  - A Comprehensive Approach to Risk Reduction for Asian and Pacific Islander
      American Women With HIV/AIDS.
AB  - As HIV incidence rises globally, Asian and Pacific Islander communities are
      increasingly affected. While often overlooked, Asian and Pacific Islander
      American women have shown the greatest percentage increase in HIV diagnosis
      rates. The development of a multilevel and multistrategy approach to HIV/AIDS
      education, prevention, and treatment among Asian and Pacific Islander females
      requires health care providers to identify personal and cultural barriers to
      prevention and treatment and implement culturally sensitive and specific
      measures. The purpose of this article is to illuminate barriers to HIV-related
      prevention, treatment, and care among Asian and Pacific Islander American females
      and provide practical application-based suggestions for providers, which may
      enhance Asian and Pacific Islander female inclusion in comprehensive HIV
      prevention. 

PMID- 24570380
TI  - Eye development in the Cape dune mole rat.
AB  - Studies on mammalian species with naturally reduced eyes can provide valuable
      insights into the evolutionary developmental mechanisms underlying the reduction
      of the eye structures. Because few naturally microphthalmic animals have been
      studied and eye reduction must have evolved independently in many of the modern
      groups, novel evolutionary developmental models for eye research have to be
      sought. Here, we present a first report on embryonic eye development in the Cape
      dune mole rat, Bathyergus suillus. The eyes of these animals contain all the
      internal structures characteristic of the normal eye but exhibit abnormalities in
      the anterior chamber structures. The lens is small but develops normally and
      exhibits a normal expression of alpha- and gamma-crystallins. One of the
      interesting features of these animals is an extremely enlarged and highly
      pigmented ciliary body. In order to understand the molecular basis of this
      unusual feature, the expression pattern of an early marker of the ciliary zone,
      Ptmb4, was investigated in this animal. Surprisingly, in situ hybridization
      results revealed that Ptmb4 expression was absent from the ciliary body zone of
      the developing Bathyergus eye. 

PMID- 24570382
TI  - Heart Disease and Depression: Is Culture a Factor?
AB  - PURPOSE: This article seeks to review and discuss the evidence linking
      depression, coronary heart disease (CHD), and culture. METHOD: PsychInfo, CINAHL,
      PubMed, and Google were searched for pertinent evidence linking depression,
      culture, and CHD, and retrieved articles were analyzed using thematic content
      analysis. FINDINGS: Identified themes were the followings: depression is a factor
      in development and prognosis of CHD and affects the capacity to self-manage and
      adhere to treatment recommendations; culture mediates mental health/illness
      representations and treatment-seeking behaviors; screening and assessment of
      depression can be affected by cultural factors; and there is a need for
      culturally appropriate screening and therapeutic strategies. DISCUSSION AND
      CONCLUSIONS: As depression is a predictor and moderating variable in the genesis
      and progression of CHD, understanding how factors such as culture affect
      screening and management of the disease is important to inform the development of
      culturally and linguistically competent strategies that ensure accurate
      screening, detection, and treatment of depression in cardiac patients in clinical
      practice.

PMID- 24570383
TI  - Therapeutic ultrasound as a treatment modality for chronic rhinosinusitis.
AB  - Chronic rhinosinusitis (CRS) is a chronic infective, inflammatory upper
      respiratory disease. While the current medical treatment of CRS focuses on the
      systemic and topical use of steroids and/or antibiotics, many bacteria residing
      on mucosal surfaces of patients with CRS exist in a biofilm state, making them
      resistant to most systemic antibiotics. Alternative therapeutic strategies that
      include blocking bacterial molecular communication, inhibiting biofilm matrix
      production and breaking down bacterial biofilms are all being explored. Physical
      therapies such as therapeutic ultrasound (US) have been advocated and utilized as
      a treatment modality for CRS for many years. US may have antiinflammatory actions
      and can also be used for the local delivery of drugs through the skin.
      Therapeutic US, which has been shown in clinical studies to be an effective
      treatment for both acute rhinosinusitis and CRS, offers significant potential in
      CRS management. 

PMID- 24570384
TI  - Interstitial lung disease in patients with rheumatoid arthritis: spontaneous and
      drug induced.
AB  - Rheumatoid arthritis (RA) is an inflammatory autoimmune disease characterized by
      the destruction of articular joint structures. RA is a systemic condition that
      often affects multiple organs, including the heart, lungs, and kidneys. Pulmonary
      complications of RA are relatively common and include pleural effusion,
      rheumatoid nodules, bronchiectasis, obliterative bronchiolitis, and opportunistic
      infections. Interstitial lung disease (ILD) is a common occurrence in patients
      with RA, and can range in severity from an asymptomatic incidental finding to a
      rapidly progressing life-threatening event. Usual interstitial pneumonia and non
      specific interstitial pneumonia are the two most common patterns, though others
      have been reported. Various disease-modifying anti-rheumatic drugs-in particular,
      methotrexate and the tumor necrosis factor-alpha inhibitors-have been associated
      with RA-ILD in numerous case reports and case series, though it is often
      difficult to distinguish association from causality. Treatment for RA-ILD
      typically involves the use of high-dose corticosteroids, often in conjunction
      with alternative immunosuppressant agents such as azathioprine or mycophenolate
      mofetil, and outcomes vary widely depending on the initial pattern of lung
      disease. Additional research into the mechanisms driving RA-ILD is needed to
      guide future therapy. 

PMID- 24570385
TI  - Perception of complex motion in humans and pigeons (Columba livia).
AB  - In the primate visual system, local motion signals are pooled to create a global
      motion percept. Like primates, many birds are highly dependent on vision for
      their survival, yet relatively little is known about motion perception in birds.
      We used random-dot stimuli to investigate pigeons' ability to detect complex
      motion (radial, rotation, and spiral) compared to humans. Our human participants
      had a significantly lower threshold for rotational and radial motion when
      compared to spiral motion. The data from the pigeons, however, showed that the
      pigeons were most sensitive to rotational motion and least sensitive to radial
      motion, while sensitivity for spiral motion was intermediate. We followed up the
      pigeon results with an investigation of the effect of display aperture shape for
      rotational motion and velocity gradient for radial motion. We found no effect of
      shape of the aperture on thresholds, but did observe that radial motion
      containing accelerating dots improved thresholds. However, this improvement did
      not reach the thresholds levels observed for rotational motion. In sum, our
      experiments demonstrate that the pooling mechanism in the pigeon motion system is
      most efficient for rotation. 

PMID- 24570386
TI  - Fast transfer of crossmodal time interval training.
AB  - Sub-second time perception is essential for many important sensory and perceptual
      tasks including speech perception, motion perception, motor coordination, and
      crossmodal interaction. This study investigates to what extent the ability to
      discriminate sub-second time intervals acquired in one sensory modality can be
      transferred to another modality. To this end, we used perceptual classification
      of visual Ternus display (Ternus in Psychol Forsch 7:81-136, 1926) to implicitly
      measure participants' interval perception in pre- and posttests and implemented
      an intra- or crossmodal sub-second interval discrimination training protocol in
      between the tests. The Ternus display elicited either an "element motion" or a
      "group motion" percept, depending on the inter-stimulus interval between the two
      visual frames. The training protocol required participants to explicitly compare
      the interval length between a pair of visual, auditory, or tactile stimuli with a
      standard interval or to implicitly perceive the length of visual, auditory, or
      tactile intervals by completing a non-temporal task (discrimination of auditory
      pitch or tactile intensity). Results showed that after fast explicit training of
      interval discrimination (about 15 min), participants improved their ability to
      categorize the visual apparent motion in Ternus displays, although the training
      benefits were mild for visual timing training. However, the benefits were absent
      for implicit interval training protocols. This finding suggests that the timing
      ability in one modality can be rapidly acquired and used to improve timing
      related performance in another modality and that there may exist a central clock
      for sub-second temporal processing, although modality-specific perceptual
      properties may constrain the functioning of this clock.

PMID- 24570387
TI  - The effect of transcranial direct current stimulation on experimentally induced
      heat pain.
AB  - Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulatory
      technique that can affect human pain perception. Placebo effects are present in
      most treatments and could therefore also interact with treatment effects in tDCS.
      The present study investigated whether short-term tDCS reduced heat pain
      intensity, stress, blood pressure and increased heat pain thresholds in healthy
      volunteers when controlling for placebo effects. Seventy-five (37 females)
      participants were randomized into three groups: (1) active tDCS group receiving
      anodal tDCS (2 mA) for 7 min to the primary motor cortex (M1), (2) placebo group
      receiving the tDCS electrode montage but only active tDCS stimulation for 30 s
      and (3) natural history group that got no tDCS montage but the same pain
      stimulation as the active tDCS and the placebo group. Heat pain was induced by a
      PC-controlled thermode attached to the left forearm. Pain intensity was
      significantly lower in the active tDCS group when examining change scores
      (pretest-posttest) for the 47  degrees C condition. The placebo group displayed
      lower pain compared with the natural history group, displaying a significant
      placebo effect. In the 43 and 45  degrees C conditions, the effect of tDCS could
      not be separated from placebo effects. The results revealed no effects on pain
      thresholds. There was a tendency that active tDCS reduced stress and systolic
      blood pressure, however, not significant. In sum, tDCS had an analgesic effect on
      high-intensity pain, but the effect of tDCS could not be separated from placebo
      effects for medium and low pain.

PMID- 24570388
TI  - The influence of a single bout of aerobic exercise on short-interval
      intracortical excitability.
AB  - Regular physical activity can have positive effects on brain function and
      plasticity. Indeed, there is some limited evidence that even a single bout of
      exercise may promote plasticity within the cortex. However, the mechanisms by
      which exercise acutely promotes plasticity are not clear. To further explore the
      effects of acute exercise on cortical function, we examined whether a single bout
      of exercise was associated with changes in cortical excitability and inhibition.
      Using standard techniques, cortical stimulus-response curves [90% resting motor
      threshold (RMT)-150% RMT] were investigated in nine subjects (four females, 31.1
      +/- 11.7 years) and short-interval intracortical inhibition (SICI) [interstimulus
      interval 2 ms and 3 ms, conditioning intensities of 80% active motor threshold
      (AMT) and 90% AMT] in 13 subjects (six females, 28.4 +/- 5.1 years) before and at
      0 and 15 min following 30 min of ergometer cycling at low-moderate or moderate
      high intensity. There were no changes in cortical excitability following exercise
      but less SICI at both 0 and 15 min post-exercise (F [2, 24] = 7.7, P = 0.003).
      These findings show that a short period of exercise can transiently reduce SICI.
      Such a change in inhibition after exercise may contribute to the development of a
      cortical environment that would be more optimal for plasticity and may partially
      explain previous findings of enhanced neuroplasticity following low-intensity
      exercise.

PMID- 24570389
TI  - Oxygen-tension controlled matrices for enhanced osteogenic cell survival and
      performance.
AB  - The success of a clinically-applicable bone tissue engineering construct for
      large area bone defects depends on its ability to allow for homogeneous bone
      regeneration throughout the construct. Insufficient vascularization, and
      consequently inadequate oxygen tension, throughout constructs has been largely
      cited as the most significant obstacle facing successful bone regeneration in
      large area defects. The development of constructs that support bone and vessel
      forming cell growth and function throughout the scaffold structure are desired
      for large-area bone defect repair. Here, we developed oxygen tension-controlled
      matrices that support more homogenous oxygen levels throughout the constructs.
      Specifically, we examined polylactic co-glycolic acid (PLGA) scaffolds with
      optimized pore distribution and the percent pore volumes, and demonstrated
      significantly decreased oxygen and pH gradient from the exterior of the construct
      to the interior after long-term cell culture in vitro. We confirmed the ability
      of these optimized constructs to support the cellular survival via live/dead
      assay. In addition, we examined their ability to support the maintenance of two
      clinically relevant progenitor cell populations for bone tissue engineering and
      vascularization, namely mesenchymal stem cells (MSCs) and endothelial progenitor
      cells (EPCs), and confirmed the expression of key bone and vascular markers via
      immunofluorescence. 

PMID- 24570390
TI  - Redirection of neurite outgrowth by coupling chondroitin sulfate proteoglycans to
      polymer membranes.
AB  - Upon nerve injury, the body creates an environment consisting of permissive and
      non-permissive cues that instruct the function of cells involved in nerve repair.
      Among other roles, the developing extracellular matrix (ECM) acts as an
      underlying substrate to guide the union of neurites extending from the proximal
      stump for bridging the nerve gap. Chondroitin sulfate proteoglycans (CSPGs) are
      present in the nerve ECM and inhibit axon growth, potentially providing molecular
      cues to prevent aberrant growth and direct regeneration. In this study, we
      examined the potential of CSPGs to guide dorsal root ganglia (DRG) neurite
      outgrowth when freely available in the media or presented from a polymeric
      membrane. Soluble CSPGs added to the media of DRG explant cultures inhibited
      neurite outgrowth without spatial bias, caused retraction of axons, and decreased
      neurite extension in a dose-dependent manner. Poly-L-lactic acid membranes were
      chemically treated to enhance adsorption of CSPGs to the surface. CSPGs bound to
      1,6-hexanediamine-treated membranes directed the orientation of neurite
      outgrowth, as neurites avoided bound CSPGs and a higher number and percentage
      grew on treated membranes lacking CSPGs. DRG explants cultured on CSPG-coated
      membranes without 1,6-hexanediamine-treatment had a smaller number of neurites
      and decreased neurite outgrowth, suggesting CSPGs were not retained on the
      membrane and were released into the culture medium. Taken together, these data
      demonstrate the potential of CSPG presentation to guide axonal growth. This
      approach offers a strategy to improve upon existing nerve guidance conduits by
      incorporating axon guidance molecules to direct nerve regeneration. 

PMID- 24570391
TI  - MicroRNA expression might predict prognosis of epithelial hepatoblastoma.
AB  - Hepatoblastoma (HB) is the most common primary liver cancer in childhood. The
      fetal and mixed embryonal/fetal epithelial subtypes of HB differ not only in
      grade of differentiation but probably also in prognosis. We aimed to determine
      microRNA (miRNA) expression patterns of the main subtypes of epithelial HBs to
      reveal differences and relate them to survival. We studied 20 cases of epithelial
      HB, subtyped as pure fetal (n = 12) or embryonal/fetal (n = 8). Tissues were
      sampled according to subtype to arrive at 15 purely fetal and eight purely
      embryonal samples (n = 8) and 15 samples of non-tumorous surrounding liver (SL).
      Relative expression of miR-17-5p, miR-18a, miR-21, miR-34a, miR-96, miR-122, miR
      181a, miR-195, miR-210, miR-214, miR-221, miR-222, miR-223, and miR-224 was
      determined by TaqMan MicroRNA Assays applying miR-140 as reference. A higher
      level of miR-18a (p < 0.01) was found in embryonal samples than in fetal samples.
      Lower miR-17-5p, miR-195, miR-210, miR-214, and higher miR-221 levels were
      detected in fetal samples (p < 0.02) in comparison with SL samples, whereas a
      lower miR-122 level was observed in embryonal samples (p < 0.003). Histological
      subtype did not correlate with survival; however, high miR-21, low miR-222, and
      low miR-224 levels proved to be independently prognostic for HB with
      significantly increased overall survival (p < 0.03). The fetal and embryonal
      components of epithelial HB, as well as SL, revealed different miRNA expression
      patterns. Furthermore, miR-21, miR-222, and miR-224 levels predict overall
      survival of HB patients regardless of epithelial subtype.

PMID- 24570392
TI  - In pulmonary lymphangioleiomyomatosis expression of progesterone receptor is
      frequently higher than that of estrogen receptor.
AB  - Lymphangioleiomyomatosis (LAM) of the lung is a rare low-grade malignancy
      affecting primarily women of childbearing age. LAM is characterized by the
      proliferation of SMA and HMB-45 positive spindle-shaped and epithelioid cells
      throughout the lung in the form of discrete lesions causing cystic destruction
      and ultimately respiratory insufficiency. LAM occurs sporadically or in patients
      with tuberous sclerosis complex (TSC) and is etiologically linked to mutations in
      the TSC1 and TSC2 genes. Although LAM cells are known to express estrogen and
      progesterone receptors (ER and PR, respectively), their respective expression
      level was never determined. Therefore, here we measured the immunohistochemical
      expression of ERs and PRs in a large series of pulmonary LAM cases using the
      Aperio Spectrum Analysis Platform. Our case series comprised open lung biopsy
      specimens from 20 LAM patients and lungs explanted during the course of lung
      transplant from 24 patients. All cases were positive for ER and PR. PR expression
      was statistically significantly higher than ER in 80 % of the biopsies while ER
      predominated only in one case. Specimens from explanted cases of LAM had
      relatively fewer PR-positive nuclei. As a result, PR expression was significantly
      higher than ER in 38 % of the cases, whereas ER predominated in 33 %. Overall, PR
      expression predominated in 57 % of cases and ER in 21 %. These data indicate that
      PR frequently prevails over ER in pulmonary LAM. LAM is unusual in its high PR/ER
      ratio; other female neoplasms show a definite prevalence of ER. Our findings
      therefore warrant further study of PR function in LAM.

PMID- 24570393
TI  - Stem cell marker-positive stellate cells and mast cells are reduced in benign
      appearing bladder tissue in patients with urothelial carcinoma.
AB  - Survival after invasive bladder cancer has improved less than that of other
      common non-skin cancers. In many types of malignancy, treatment failure has been
      attributed to therapy-resistant stem-like cancer cells. Our aim was therefore to
      determine identities of stem cell marker-positive cells in bladder cancer tissue
      and to investigate possible associations between these cells and different forms
      of bladder neoplasia. We investigated tissue from 52 patients with bladder
      neoplasia and 18 patients with benign bladder conditions, from a cohort that had
      been previously described with regard to diagnosis and outcome. The samples were
      analysed immunohistologically for the stem cell markers aldehyde dehydrogenase 1
      A1 (ALDH1) and CD44, and markers of cell differentiation. The majority of stem
      cell marker-positive cells were located in connective tissue, and a smaller
      fraction in epithelial tissue. Stem cell marker-positive cells exhibiting
      possible stem cell characteristics included cells in deeper locations of benign
      and malignant epithelium, and sub-endothelial cells in patients with or without
      neoplasia. Stem cell marker-positive cells with non-stem cell character included
      stellate cells, mast cells, endothelial cells, foamy histiocytes, and neurons.
      Significantly, ALDH1+ stellate cells and ALDH1+ mast cells were reduced in number
      in stroma of benign-appearing mucosa of bladder cancer patients. The stem cell
      markers ALDH1 and CD44 label several types of differentiated cells in bladder
      tissue. ALDH1+ stellate cells and mast cells appear to be reduced in stroma of
      normal-appearing mucosa of bladder cancer patients, and may be part of a "field
      effect" in cancer-near areas.

PMID- 24570395
TI  - One Health and paradigms of public biobanking.
AB  - In this paper, the authors consider the idea of the public biobank governance
      framework with respect to the innovative paradigm of One Health. The One Health
      initiative has been defined as an integrative and interdisciplinary effort to
      improve the lives and well-being of human beings and non-human animals, as well
      as to preserve the environment. Here, we use this approach as a starting
      presumption with respect to institutional design. We examine the theoretical and
      legal framework underlying the concept of biobanking that, being public
      orientated, is for the public good. We suggest that this account of research
      practice does not ethically correlate with One Health principles. Instead, we
      argue that One Health requires a model of biobanking that is based on universal
      goods, that is, goods that serve human beings as well as non-human animals and
      the environment, and which we define in detail. Our purpose is to begin a
      discussion on how One Health principles might be implemented in health
      initiatives. 

PMID- 24570394
TI  - The interleukin-17 pathway in psoriasis and psoriatic arthritis: disease
      pathogenesis and possibilities of treatment.
AB  - Psoriasis and psoriatic arthritis (PsA) are pathophysiological enigmas among
      rheumatic diseases. Substantial clinical advances have been made with new therapy
      targeting different components of the IL-17 and IL-23 pathways. At the same time,
      an increase in research on the topic has provided new insights into the potential
      functional effects of treatments on cell types, pathways, and tissues of
      interest. Here we review our knowledge of all IL-17 family members, their
      relationships with the IL-23 pathway, and the outcomes of relevant clinical
      trials in which different strategies for targeting these molecules have been
      tested in the treatment of moderate to severe psoriasis and PsA. 

PMID- 24570396
TI  - Morally relevant potential.
AB  - Fetuses and infants are said to warrant protecting because of their potential.
      But valuing potential supposedly leads to absurdities like protecting cells that
      could be technologically altered to develop into persons. This can be avoided by
      recognising that morally relevant potential is determined by what is presently
      healthy development (proper functioning) for an organism. The only interests of
      mindless organisms are in the flourishing that necessarily depends upon their
      healthy functioning. They can be harmed when those interests are frustrated. We
      criticise McMahan for claiming that harm is instead a function of the degree of
      psychological ties to the future. 

PMID- 24570397
TI  - Ras-dva1 small GTPase regulates telencephalon development in Xenopus laevis
      embryos by controlling Fgf8 and Agr signaling at the anterior border of the
      neural plate.
AB  - We previously found that the small GTPase Ras-dva1 is essential for the
      telencephalic development in Xenopus laevis because Ras-dva1 controls the Fgf8
      mediated induction of FoxG1 expression, a key telencephalic regulator. In this
      report, we show, however, that Ras-dva1 and FoxG1 are expressed in different
      groups of cells; whereas Ras-dva1 is expressed in the outer layer of the anterior
      neural fold, FoxG1 and Fgf8 are activated in the inner layer from which the
      telencephalon is derived. We resolve this paradox by demonstrating that Ras-dva1
      is involved in the transduction of Fgf8 signal received by cells in the outer
      layer, which in turn send a feedback signal that stimulates FoxG1 expression in
      the inner layer. We show that this feedback signal is transmitted by secreted Agr
      proteins, the expression of which is activated in the outer layer by mediation of
      Ras-dva1 and the homeodomain transcription factor Otx2. In turn, Agrs are
      essential for maintaining Fgf8 and FoxG1 expression in cells at the anterior
      neural plate border. Our finding reveals a novel feedback loop mechanism based on
      the exchange of Fgf8 and Agr signaling between neural and non-neural compartments
      at the anterior margin of the neural plate and demonstrates a key role of Ras
      dva1 in this mechanism. 

PMID- 24570399
TI  - Impact of the 2011 Great East Japan Earthquake and Tsunami on functional
      disability among older people: a longitudinal comparison of disability prevalence
      among Japanese municipalities.
AB  - OBJECTIVE: To examine the hypothesis that disability prevalence has increased to
      a greater degree in the areas severely affected by the earthquake and tsunami of
      11 March 2011 than in other areas. METHODS: Longitudinal analysis using public
      statistics data from the Ministry of Health, Labour and Welfare in Japan. The
      analysis included 1549 municipalities covered by the Long-term Care Insurance
      (LTCI) system. 'Disaster areas' were defined as three prefectures (Iwate, Miyagi,
      Fukushima). The outcome measure was the number of aged people (>=65 years) with
      LTCI disability certification. Rates of change in disability prevalence from
      February 2011 to February 2012 were used as the primary outcome variable, and
      were compared by analysis of covariance between 'Coastal disaster areas', 'Inland
      disaster areas' and 'Non-disaster areas'. RESULTS: Regarding disability
      prevalence at all levels, the mean value of the increase rate in Coastal disaster
      areas (7.1%) was higher than in Inland disaster areas (3.7%) and Non-disaster
      areas (2.8%) (p<0.001). CONCLUSIONS: The areas that were severely affected by the
      earthquake and tsunami had a significantly higher increase in disability
      prevalence during the 1 year after the earthquake disaster than other areas.

PMID- 24570398
TI  - Oncogenic mutations produce similar phenotypes in Drosophila tissues of diverse
      origins.
AB  - An emerging interest in oncology is to tailor treatment to particular cancer
      genotypes, i.e. oncogenic mutations present in the tumor, and not the tissue of
      cancer incidence. Integral to such a practice is the idea that the same oncogenic
      mutation(s) produces similar outcomes in different tissues. To test this idea
      experimentally, we studied tumors driven by a combination of Ras(V12) and
      scrib(1) mutations in Drosophila larvae. We found that tumors induced in tissues
      of neural ectodermal and mesodermal origins behaved similarly in every manner
      examined: cell cycle checkpoints, apoptosis, cellular morphology, increased
      aneuploidy and response to Taxol. We conclude that oncogenic effects override
      tissue-specific differences, at least for the mutations, tissues, and phenotypes
      studied herein. 

PMID- 24570400
TI  - Effectiveness of different farrowing induction protocols in sows using
      alphaprostol on day 114 of gestation.
AB  - Farrowing induction in sows is frequently applied and different protocols were
      described. Most studies induce farrowing between day 111 and 113 of gestation,
      but hardly any later during gestation. The aim of this study was to investigate
      the effects of different induction protocols when applied on d114 of gestation.
      We randomly assigned 118 sows to four treatment groups: single injection of
      prostaglandin (1*PG), prostaglandin combined with oxytocin 24 hours later
      (PG+OT), half the dosage of prostaglandin twice with six hours interval
      (2*1/2PG), and a control group of which farrowing wasn't induced. All injections
      were administered intramuscularly in the neck on day 114 of gestation. A
      significantly higher percentage of sows started farrowing between 22 and 32 hours
      after induction in the PG+OT-group (68 per cent) and the 2*1/2PG-group (52 per
      cent) compared to the control group (23 per cent). The 1*PG-group (46 per cent)
      tended to differ from the control group (P=0.087). More sows from the PG+OT-group
      were constipated at farrowing (P=0.042). Farrowing duration, birth interval, per
      cent stillborn piglets, dystocia and other variables were similar between the
      groups. In the present herd and with continuous farrowing supervision, applying
      PG+OT or 2*1/2PG on d114 of gestation was efficient to induce onset of farrowing
      in most of the sows 22-32 hours after induction without considerable negative
      effects. 

PMID- 24570401
TI  - Survey of the UK veterinary profession: common species and conditions nominated
      by veterinarians in practice.
AB  - The practice of evidence-based veterinary medicine involves the utilisation of
      scientific evidence for clinical decision making. To enable this, research topics
      pertinent to clinical practice need to be identified, and veterinary clinicians
      are best placed to do this. The main aim of this study was to describe the
      veterinary population, the common species and conditions veterinary clinicians
      nominated they saw in practice and how much information clinicians perceived was
      available in the literature for these. A questionnaire was distributed to all
      Royal College of Veterinary Surgeons registered veterinarians agreeing to be
      contacted for research purposes (n=14,532). A useable response rate of 33 per
      cent (4842/14,532) was achieved. The most commonly seen species reported by vets
      were dogs, cats and rabbits followed by equines and cattle. Overall, skin
      conditions were most commonly mentioned for small animals, musculoskeletal
      conditions for equines and reproduction conditions for production animals.
      Veterinary clinicians perceived there was a higher level of information available
      in the literature for conditions in dogs, cattle and equines and lower levels for
      rabbits and guinea pigs. The results from this study can be used to help define
      the research needs of the profession to aid the incorporation of evidence in
      veterinary practice. 

PMID- 24570402
TI  - Accuracy of distal limb fracture diagnosis at British racecourses 1999-2005.
AB  - Accurate diagnosis of racing injuries can be difficult. The objectives of this
      study were to describe the postmortem (PM) defined distribution of fatal distal
      limb fractures (DLF) affecting Thoroughbreds racing in Great Britain between
      February 1999 and August 2005 and then assess the accuracy of veterinary
      racecourse diagnoses and examine whether these improved following introduction of
      a computerised recording system. PM examinations were performed on limbs distal
      to radius or tibia from all cases of fatal DLF occurring on British racecourses
      during the study period. Results of these examinations were described and
      compared with the diagnoses made at the racecourses. Over the study period, fatal
      DLF prevalence in all race types was 0.63 per 1000 starts (344/545,335), with the
      lowest frequency (0.34 per 1000 starts) in flat racing on turf and the highest
      frequency (1.56 per 1000 starts) in national hunt flat races. The prevalence of
      fatal DLF in steeplechase racing had reduced from that reported previously: from
      2.3 to 1 per 1000 starts. Racecourse veterinary identification of fracture
      presence was good (>93 per cent); however, identification of all fractured bones
      was poor (<55 per cent). Introduction of a computerised recording system did not
      significantly improve diagnostic accuracy. The prevalence of fatal DLF has not
      significantly altered since the 1970s. Techniques such as on course digital
      radiography to help improve racecourse fracture diagnoses could be introduced. 

PMID- 24570403
TI  - Encephalitozoon cuniculi in rabbits in Germany: prevalence and sensitivity of
      antibody testing.
AB  - The aim of this study was to investigate the prevalence of Encephalitozoon
      cuniculi antibodies in healthy and diseased rabbits in Germany. Age and gender
      dependencies were taken into consideration. The sensitivity of the E cuniculi
      antibody test and its relevance for the diagnosis of E cuniculi infection in
      rabbits was also examined. A total of 773 healthy and diseased rabbits were
      tested for E cuniculi antibodies (indirect immune fluorescence antibody test
      (IFAT) or carbon immunoassay (CIA). No differences between diseased and healthy
      rabbits were observed with regard to gender, but diseased rabbits were
      significantly older (P>0.001). Forty-three percent (336/773) of all rabbits were
      positive for E cuniculi antibodies. Of the diseased rabbits, 48 per cent
      (266/555) were positive for E cuniculi antibodies. While 96 per cent (91/95) of
      the rabbits with histopathologically or PCR confirmed encephalitozoonosis were E
      cuniculi antibody-positive, only 60 per cent (144/241) of the rabbits suspected
      of E cuniculi infection were antibody-positive. Of the healthy rabbits, 18 per
      cent (39/218) were positive for E cuniculi antibodies. Diseased rabbits were
      almost three times more likely to be E cuniculi antibody-positive than healthy
      ones (P>0.001; relative risk (RR): 2.68; 95% CI 1.99 to 3.61). The sensitivity of
      the E cuniculi antibody test was 96 per cent.

PMID- 24570404
TI  - Detection of the human-pandemic Escherichia coli B2-O25b-ST131 in UK dogs.

PMID- 24570405
TI  - Identification and characterisation of a novel genogroup II picobirnavirus in a
      calf in India.

PMID- 24570406
TI  - An epidemiological study of diabetes mellitus in dogs attending first opinion
      practice in the UK.
AB  - This study aimed to estimate the prevalence of canine diabetes mellitus (DM) in
      primary-care clinics in England, to identify risk factors associated with DM and
      to describe the survival of affected dogs. Cases of DM were identified within the
      electronic patient records of 89 small-animal practices. A nested case-control
      study identified risk factors for the diagnosis of DM using logistic regression
      models. Cox proportional hazards models were used to analyse variables associated
      with survival. Four-hundred and thirty-nine canine DM cases were identified,
      giving an apparent prevalence of 0.34% (95% CI 0.31% to 0.37%). Neutered males
      were at an increased risk of diabetes compared with entire males, whereas
      neutering was not associated with DM in females. When compared with crossbred
      dogs, Yorkshire terriers had increased odds, whereas German shepherd dogs and
      golden retrievers had lower odds of DM. Being classified as overweight and having
      a diagnosis of pancreatitis, hyperadrenocorticism or a urinary tract infection
      were positively associated with DM. Older dogs and those diagnosed with
      pancreatitis had a higher hazard of death, whereas insured and neutered dogs had
      a lower hazard. This study provides an objective assessment of canine DM using
      primary-care veterinary practice data and is a valuable benchmark against which
      future epidemiological trends in DM can be assessed and improvements in the
      management of DM in primary-care practice can be judged.

PMID- 24570407
TI  - Use of plasma samples to assess passive transfer in calves using refractometry:
      comparison with serum and clinical cut-off point.

PMID- 24570408
TI  - Fertility after fetotomy: a clinical study focusing on heavy draft mares.
AB  - Although fetotomy is recommended for all mares when the fetus is dead and
      difficult to extract, little has been written about fetotomy and heavy draft
      mares. This lack includes indications for fetotomy in heavy draft mares,
      differences in treatment and prognosis of heavy mares kept by farmers of low
      socioeconomic status, and how this procedure affects the mare's further
      fertility. The literature on mares, in general, also differs on the survival rate
      of mares that undergo fetotomy, the prevalence of postpartum complications, and
      further fertility. To answer these questions, we reviewed the medical records of
      102 mares that underwent fetotomy, mostly heavy draft mares (n=93). Head
      malposture (62.7 per cent) was the most common fetal maldisposition, which
      required fetotomy in all cases. The survival rate was 84.3 per cent (n=86). The
      most common postpartum complications were endometritis puerperalis (32.5 per
      cent) and retained placenta (27.9 per cent). 61 mares (70.9 per cent) both showed
      foal heat and cycled regularly in the first season after fetotomy. Out of 45
      mares that were bred in the first season, 14 became pregnant (31.1 per cent).
      Survival rate and further fertility were reduced by delayed requests for
      veterinary assistance due to the difficult economic situation of the owners.
      Fetotomy is the method of choice for serious maldispositions, especially head
      malpostures, because in contrast with cesarean sections, it has a higher survival
      rate and allows the mare to return to breeding in the same season. 

PMID- 24570409
TI  - Legislation allowing dairy farmers to treat milk fever with intravenous calcium
      results in more treatments and lower case fatality.

PMID- 24570410
TI  - Investigation of the use of pooled faecal and environmental samples following an
      enrichment step for the detection of Salmonella enterica by real-time PCR.

PMID- 24570411
TI  - Leptospira cases and vaccination habits within UK vet-visiting dogs.

PMID- 24570412
TI  - Efficient identification of context dependent subgroups of risk from genome-wide
      association studies.
AB  - We have developed a modified Patient Rule-Induction Method (PRIM) as an
      alternative strategy for analyzing representative samples of non-experimental
      human data to estimate and test the role of genomic variations as predictors of
      disease risk in etiologically heterogeneous sub-samples. A computational limit of
      the proposed strategy is encountered when the number of genomic variations
      (predictor variables) under study is large (>500) because permutations are used
      to generate a null distribution to test the significance of a term (defined by
      values of particular variables) that characterizes a sub-sample of individuals
      through the peeling and pasting processes. As an alternative, in this paper we
      introduce a theoretical strategy that facilitates the quick calculation of Type I
      and Type II errors in the evaluation of terms in the peeling and pasting
      processes carried out in the execution of a PRIM analysis that are under
      estimated and non-existent, respectively, when a permutation-based hypothesis
      test is employed. The resultant savings in computational time makes possible the
      consideration of larger numbers of genomic variations (an example genome-wide
      association study is given) in the selection of statistically significant terms
      in the formulation of PRIM prediction models.

PMID- 24570413
TI  - Ion age transport: developing devices beyond electronics.

PMID- 24570414
TI  - Voltage gated ion and molecule transport in engineered nanochannels: theory,
      fabrication and applications.
AB  - Nanochannels remain at the focus of growing scientific and technological
      interest. The nanometer scale of the structure allows the discovery of a new
      range of phenomena that has not been possible in traditional microchannels, among
      which a direct field effect control over the charges in nanochannels is very
      attractive for various applications, since it offers a unique opportunity to
      integrate wet ionics with dry electronics seamlessly. This review will focus on
      the voltage gated ionic and molecular transport in engineered gated nanochannels.
      We will present an overview of the transport theory. Fabrication techniques
      regarding the gated nanostructures will also be discussed. In addition, various
      applications using the voltage gated nanochannels are outlined, which involves
      biological and chemical analysis, and energy conversion. 

PMID- 24570415
TI  - Modeling as a research tool in poultry science.
AB  - The World's Poultry Science Association (WPSA) is a long-established and unique
      organization that strives to advance knowledge and understanding of all aspects
      of poultry science and the poultry industry. Its 3 main aims are education,
      organization, and research. The WPSA Keynote Lecture, titled "Modeling as a
      research tool in poultry science," addresses 2 of these aims, namely, the value
      of modeling in research and education. The role of scientists is to put forward
      and then to test theories. These theories, or models, may be simple or highly
      complex, but they are aimed at improving our understanding of a system or the
      interaction between systems. In developing a model, the scientist must take into
      account existing knowledge, and in this process gaps in our knowledge of a system
      are identified. Useful ideas for research are generated in this way, and
      experiments may be designed specifically to address these issues. The resultant
      models become more accurate and more useful, and can be used in education and
      extension as a means of explaining many of the complex issues that arise in
      poultry science. 

PMID- 24570416
TI  - Extended survival times of Mycoplasma gallisepticum and Mycoplasma synoviae on
      kanekalon synthetic hair fibres.
AB  - The survival times of Mycoplasma gallisepticum (Mg) and Mycoplasma synoviae (Ms)
      on washed and unwashed natural and synthetic kanekalon hair samples over a 5-d
      period were evaluated using the color changing unit method for comparison with
      results of previous studies conducted on natural hair. Regardless of whether
      synthetic or natural hair samples prewashed with a disinfectant shampoo were
      spiked with Mg or Ms, all viable organisms rapidly dropped below a count of 1 *
      10(1)/mL of culture. Unwashed natural hair seeded with a titer of approximately 1
      * 10(6)/mL of viable Mg or Ms decreased to 6 * 10(5)/mL and 6 * 10(3)/mL,
      respectively, by 4 h postseeding, but no viable Mg or Ms were detected on natural
      hair from 8 h onwards. By contrast, the titers of Mg and Ms on synthetic hair did
      not decline from the initial 1 * 10(6)/mL seed dose up to 96 h postseeding, and,
      in fact, viable Mg and Ms was still detectable at 9 d postinfection. Application
      of a real-time quantitative single-tube duplex PCR assay confirmed that no
      proliferation of Mg or Ms had occurred on the synthetic hair samples, the cells
      simply remained viable. The unexpected finding that Mg and Ms survive for
      extended periods on synthetic kanekalon hair fibers raises the question of
      whether attachment to a surface is a prerequisite for the survival and
      persistence of Mg and Ms in the extra-host environment. Future studies should be
      aimed at determining whether other synthetic hair types or indeed other types of
      plastics commonly found in the poultry house offer similar survival advantages to
      mycoplasmas. 

PMID- 24570417
TI  - Mutations in the Cyp51A gene and susceptibility to itraconazole in Aspergillus
      fumigatus isolated from avian farms in France and China.
AB  - Azole resistance in the fungal pathogen Aspergillus fumigatus is an emerging
      problem and may develop during azole therapy in humans and animals or exposure to
      azole fungicides in the environment. To assess the potential risk of azole
      resistance emergence in avian farms where azole compounds are used for the
      control of avian mycoses, we conducted a drug susceptibility study including A.
      fumigatus isolates from birds and avian farms in France and Southern China. A
      total number of 175 isolates were analyzed: 57 isolates were collected in France
      in avian farms where chemoprophylaxis with parconazole was performed; 51 isolates
      were collected in southern China in avian farms where no chemoprophylaxis was
      performed; and 67 additional isolates came from the collection of a mycology
      laboratory. No resistant isolate was detected, and the distribution of minimum
      inhibitory concentrations was similar for isolates collected in farms with or
      without azole chemoprophylaxis. For 61 randomly selected isolates, the full
      coding sequence of the Cyp51A gene was determined to detect mutations. Nine amino
      acid alterations were found in the target enzyme, 3 of which were new. 

PMID- 24570418
TI  - Thirty-four generations of divergent selection for 8-week body weight in
      chickens.
AB  - Chickens of the Slovenian commercial Prelux-bro line were divergently selected
      over 34 generations for high and low BW at 8 wk of age. The aim of the study was
      to estimate responses to selection with a nonlinear model. Estimates of BW for
      each generation were provided by the mixed model. For fitting generation means
      against generation or cumulative selection differential, an exponential model was
      used. Estimates of realized heritability over generations were derived from
      regression of the response on cumulative selection differential. After 34
      generations, the lines differed by approximately 2,220 g for males and 1,860 g
      for females. Estimates for a selection limit in the high line were 2,598.4 and
      2,144.1 g, for males and females, respectively. A selection limit was not reached
      in the low line. Half of the selection response was obtained after approximately
      6 to 8 generations in the high line and 20 to 28 generations in the low line.
      Estimated realized heritability decreased over generations. Heritability was
      larger for females than males and reduction of heritability was more rapid in the
      high line than in the low line. Genetic SD decreased over generations. Phenotypic
      SD increased over generations in the high line, but was constant in the low line
      in the initial 22 generations and decreased thereafter. According to the good fit
      of the nonlinear model and informative parameter estimates, the results confirmed
      the usefulness of the nonlinear model for analyzing responses to long-term
      selection. 

PMID- 24570419
TI  - Genetic parameter estimates of growth curve and reproduction traits in Japanese
      quail.
AB  - The goal of selection studies in broilers is to obtain genetically superior
      chicks in terms of major economic traits, which are mainly growth rate, meat
      yield, and feed conversion ratio. Multiple selection schedules for growth and
      reproduction are used in selection programs within commercial broiler dam lines.
      Modern genetic improvement methods have not been applied in experimental quail
      lines. The current research was conducted to estimate heritabilities and genetic
      correlations for growth and reproduction traits in a Japanese quail flock. The
      Gompertz equation was used to determine growth curve parameters. The Gibbs
      sampling under a multi-trait animal model was applied to estimate the
      heritabilities and genetic correlations for these traits. A total of 948 quail
      were used with complete pedigree information to estimate the genetic parameters.
      Heritability estimates of BW, absolute and relative growth rates at 5 wk of age
      (AGR and RGR), beta0 and beta2 parameters, and age at point of inflection (IPT)
      of Gompertz growth curve, total egg number (EN) from the day of first lay to 24
      wk of age were moderate to high, with values ranging from 0.25 to 0.40. A low
      heritability (0.07) for fertility (FR) and a strong genetic correlation (0.83)
      between FR and EN were estimated in our study. Body weight exhibited negative
      genetic correlation with EN, FR, RGR, and IPT. This genetic antagonism among the
      mentioned traits may be overcome using modern poultry breeding methods such as
      selection using multi-trait best linear unbiased prediction and crossbreeding. 

PMID- 24570420
TI  - An association between genetic variation in the roundabout, axon guidance
      receptor, homolog 2 gene and immunity traits in chickens.
AB  - The roundabout, axon guidance receptor, homolog 2 (ROBO2) gene is one member of
      the roundabout (ROBO) family, which belongs to the immunoglobulin superfamily.
      The ROBO molecules are known to function in axon guidance and cell migration and
      are involved in SLIT/ROBO signaling. In this study, we obtained the full-length
      cDNA sequence of the chicken ROBO2 gene. Sequence analysis indicated that 3 SNP
      (1418G > A, 1421C > A and 2462T > C) exist in exons 5 and 12 of the ROBO2 gene.
      Genotyping results revealed that the allele frequency of SNP 1421C > A was
      similar in all tested breeds, but the allele frequencies of the other 2 SNP were
      different between White Leghorn and Chinese indigenous chickens. Allele G of
      1418G > A and allele T of 2462T > C predominated in the Chinese indigenous breed,
      whereas alleles A and C predominated in the White Leghorn breed. Association
      analyses revealed that birds with the GG genotype of SNP 1418G > A or the TT
      genotype of SNP 2462T > C had significantly higher antibody responses to
      Newcastle disease virus (NDV_S/P; P < 0.01) than carriers of the A allele (GA and
      AA) or the C allele (TC), respectively. Real-time PCR further revealed that ROBO2
      expression in the spleens of the birds with higher antibody responses (GG and TT
      genotypes at SNP 1418 and 2462, respectively) was significantly higher than in
      the spleens of birds with the AA and AG genotypes at SNP 1418 or the TC genotype
      at SNP 2462 (P < 0.01). The results demonstrated that genetic variation at the
      ROBO2 gene plays a key role in the immune response to Newcastle disease virus,
      and SNP 1418G > A and 2462T > C can be used as genetic markers for the selection
      of chickens with stronger immune responses to Newcastle disease virus. 

PMID- 24570421
TI  - Immune response of broiler chickens immunized orally with the recombinant
      proteins flagellin and the subunit B of cholera toxin associated with
      Lactobacillus spp.
AB  - This study investigated the immune response of broiler chickens with oral
      treatment of a Lactobacillus spp. pool (PL) associated with microencapsulated
      recombinant proteins flagellin (FliC) and the subunit B of cholera toxin (CTB).
      Immune responses were evaluated by measuring IgA from intestinal fluid, serum
      IgY, and immunostaining of CD8(+) T lymphocytes present in the cecum. The
      evaluations were performed on d 0, 7, 14, 21, and 28 posttreatment. A significant
      increase (P < 0.05) was observed in IgA levels in all immunized groups,
      especially 3 wk after immunization. Treatments 2 (recombinant CTB) and 3
      (recombinant FliC+CTB) showed the highest concentrations. Similarly, serum
      concentrations IgY (MUg/mL) increased along the experiment, and the means for
      treatments 2 and 3 showed significant differences (P < 0.05) compared with
      controls, reaching concentrations of 533 and 540 MUg/mL, respectively. The number
      of CD8(+) T lymphocytes in all treatments greatly differed (P < 0.05) compared
      with the negative control at 21 d posttreatment. However, only treatment 2
      (recombinant CTB), 4 (PL), and 5 (recombinant FliC+ recombinant CTB + PL)
      remained significantly (P < 0.05) different from the control at 28 d
      posttreatment. Thus, it is concluded that the microencapsulated recombinant
      proteins administered orally to broiler chickens are capable of stimulating
      humoral and cellular immune response, and the combinations of these antigens with
      Lactobacillus spp. can influence the population of CD8(+) T cells residing in the
      cecum. 

PMID- 24570422
TI  - Effects of Clostridium butyricum on growth performance, immune function, and
      cecal microflora in broiler chickens challenged with Escherichia coli K88.
AB  - This study was conducted to investigate the effects of Clostridium butyricumon
      growth performance, immune function, and cecal microflora in broiler chickens
      challenged with Escherichia coli K88. Three hundred sixty 1-d-old broiler
      chickens were randomly divided into 4 treatments: negative control (NC) birds
      were fed a basal diet and not challenged with E. coli K88; positive control (PC)
      birds were fed a basal diet and challenged with E. coli K88; C. butyricum
      treatment (CB) birds were fed a diet containing 2 * 10(7) cfu C. butyricum/kg of
      diet and challenged with E. coli K88; and colistin sulfate treatment (CS) birds
      were fed a diet containing 20 mg of colistin sulfate/kg of diet and challenged
      with E. coli K88. Birds fed CB had greater (P < 0.05) BW than the PC birds from 3
      to 21 d postchallenge. Birds fed CB had greater (P < 0.05) serum IgA and IgY at
      14 d postchallenge, greater (P < 0.05) serum IgM at 21 d postchallenge, and
      greater (P < 0.05) mucosal secreted IgA at 3 and 7 d postchallenge than the PC
      birds. Birds fed CB had greater concentrations of serum complement component 3 at
      14 d postchallenge, and greater (P < 0.05) concentrations of serum complement
      component 4 at 3, 7, and 14 d postchallenge than the PC birds. Birds in the CS or
      CB treatments had less cecal E. coli population at 3, 7, and 21 d postchallenge,
      and less cecal Clostridium perfringens counts at 21 d postchallenge compared with
      the PC birds. The CB treatment increased (P < 0.05) the population of cecal
      Lactobacillus at 3 d postchallenge and the number of cecal Bifidobacterium at 3,
      14, and 21 d postchallenge in comparison with the PC treatment. The results
      indicate that dietary supplementation of CB promotes growth performance, improves
      immune function, and benefits the cecal microflora in Escherichia coli K88
      challenged chickens. 

PMID- 24570423
TI  - Resveratrol induces antioxidant and heat shock protein mRNA expression in
      response to heat stress in black-boned chickens.
AB  - This study investigated the effects of dietary resveratrol at 0, 200, 400, or 600
      mg/kg of diet on the performance, immune organ growth index, serum parameters,
      and expression levels of heat shock protein (Hsp) 27, Hsp70, and Hsp90 mRNA in
      the bursa of Fabricius, thymus, and spleen of 42-d-old female black-boned
      chickens exposed to heat stress at 37 +/- 2 degrees C for 15 d. The results
      showed that heat stress reduced daily feed intake and BW gain; decreased serum
      glutathione (GSH), growth hormone, and insulin-like growth factor-1 levels; and
      inhibited GSH peroxidase (GSH-Px), superoxide dismutase (SOD), and catalase (CAT)
      activities compared with birds subjected to thermo-neutral circumstances.
      Chickens that were fed diets supplemented with resveratrol exhibited a linear
      increase in feed intake and BW gain (P < 0.001); serum GSH, growth hormone, and
      insulin-like growth factor-1 levels (P <= 0.01); and GSH-Px, SOD, and CAT
      activities (P < 0.001) compared with chickens that were fed diets without
      resveratrol during heat stress. In contrast, serum malonaldehyde concentrations
      were decreased (P < 0.001) in the chickens fed a resveratrol-supplemented diet.
      Heat stress also reduced (P < 0.05) the growth index of the bursa of Fabricus and
      spleen; however, it had no effect on the growth index of the thymus. The growth
      index of the bursa of Fabricius and spleen increased (P < 0.05) upon heat stress
      and coincided with an increase in supplemental resveratrol levels. The expression
      of Hsp27, Hsp70, and Hsp90 mRNA in the bursa of Fabricius and spleen were
      increased (P < 0.01), but those of Hsp27 and Hsp90 mRNA in thymus were decreased
      (P < 0.01) under heat stress compared with no heat stress. Resveratrol attenuated
      the heat stress-induced overexpression of Hsp27, Hsp70, and Hsp90 mRNA in the
      bursa of Fabricius and spleen and increased the low expression of Hsp27 and Hsp90
      mRNA in thymus upon heat stress. The results suggest that supplemental
      resveratrol improves growth performance and reduces oxidative stress in heat
      stressed black-boned chickens by increasing serum growth hormone concentrations
      and modulating the expression of heat shock genes in organs of the immune system.

PMID- 24570424
TI  - The stimulatory effect of different CpG oligonucleotides on the maturation of
      chicken bone marrow-derived dendritic cells.
AB  - CpG oligonucleotide (CpG-ODN) can exert an immunostimulatory effect on different
      types of immune cells such as dendritic cells (DC). The immunostimulatory
      activity of CpG-ODN is closely related to its nucleotide sequence and structural
      characteristics. In this study, we aimed at evaluating the stimulatory effects of
      different CpG-ODN on the maturation of chicken bone marrow-derived DC (BM-DC) in
      vitro. First, 4 CpG-ODN were designed. Then chicken bone marrow cells were
      extracted from tibia and femur and cultured in the RPMI 1640 medium with
      recombinant chicken granulocyte-macrophage colony-stimulating factor (GM-CSF) and
      IL-4. After culture for 6 d, the cells were stimulated by different CpG-ODN or
      lipopolysaccharide for 24 h. Finally, the effects of different CpG-ODN on the
      maturation of chicken BM-DC were investigated by morphologic, phenotypic, and
      functional assays. The results showed that the cultured cells could display the
      typical DC morphology, and the CpG-ODN could efficiently stimulate the BM-DC to
      show the mature morphologic characteristics and upregulate the expression of
      cluster of differentiation (CD) 40 and CD86 molecules. In addition, after
      stimulation by CpG-ODN, the BM-DC could significantly induce T-cell proliferative
      response (P < 0.01). Among all the sequences, the stimulatory effect of CpG-ODN
      F3 with an addition of poly-guanosine strings at the 3' end was the best on the
      chicken BM-DC. In conclusion, this is the first report to demonstrate that
      different CpG-ODN have distinct stimulatory effects on the maturation of chicken
      BM-DC and CpG-ODN F3 with the best stimulatory effect can be a potent stimulant
      for the maturation of chicken BM-DC. 

PMID- 24570425
TI  - Evaluation of changes induced by temperature, contact time, and surface in the
      efficacies of disinfectants against avian influenza virus.
AB  - Avian influenza viruses (AIV) are highly susceptible to all disinfectants because
      they are enveloped viruses. Disinfectants effective against AIV have optimum
      efficacies at temperatures above 20 degrees C. Very few studies on effective
      disinfectants at low temperatures have been done. Disinfectants were investigated
      at 4 different temperatures (25, 4, 0, and -10 degrees C) and 2 contact times (1
      and 5 min) with suspension tests. Virucidal activity of the disinfectants was
      evaluated by carrier tests (wood and stainless steel) at 25 and -10 degrees C.
      The concentration of each disinfectant for efficient disinfection within a short
      time (<1 min) at 25 and -10 degrees C was also reestablished. The results from
      the suspension test indicated that low temperatures inhibited the virucidal
      efficacy of citric acid (CA) and CA + quaternary ammonium compounds (CA+ QAC) for
      1 and 5 min, whereas the remaining disinfectants were effective, regardless of
      the short contact times and low temperatures. The carrier test results suggested
      that dried virus on wood was more difficult to inactivate compared with that on
      stainless steel. However, sodium dichloroisocyanurate and glutaraldehyde could
      inactivate AIV on both wood and stainless steel at -10 degrees C. Citric acid
      based agents could not sufficiently inactivate AIV at -10 degrees C; however, the
      limitation due to low temperatures was overcome by adjusting disinfectant
      concentration. For a successful disinfection during winter, the disinfectants
      that could have short contact times with optimum efficacy against the target
      organism should be selected. 

PMID- 24570426
TI  - The influence of genetic background versus commercial breeding programs on
      chicken immunocompetence.
AB  - Immunocompetence of livestock plays an important role in farm profitability
      because it directly affects health maintenance. Genetics significantly influences
      the immune system, and the genotypic structure of modern fast-growing chickens
      has been changed, particularly after decades of breeding for higher production.
      Therefore, this study was designed to help determine if intensive breeding
      programs have adversely affected immunocompetence or whether the immune response
      profiles are controlled to greater extent by genetic background. Thus, 3
      indigenous chicken populations from different genetic backgrounds and 2 globally
      available modern broiler strains, Ross 308 and Cobb 500, were evaluated for
      various aspects of immune response. These included antibody responses against
      sheep red blood cells and Brucella abortus antigen, as well as some aspects of
      cell-mediated immunocompetence by toe web swelling test and in vitro blood
      mononuclear cell proliferation. Significant differences (P < 0.05) in antibody
      responses to both antigens and cellular proliferation were observed among
      populations but not consistently between modern commercial strains versus the
      indigenous populations. In fact, the immune response profiles of Cobb 500 were
      similar to the indigenous populations, but varied compared with the other
      commercial strain. In addition, considerable variation was recorded between
      indigenous populations for all responses measured in this study. The results of
      this study suggest that the variation observed in immune responses between these
      strains of chickens is most likely due to differences in the genetic background
      between each strain of chicken rather than by commercial selection programs for
      high production. 

PMID- 24570427
TI  - 2-Hydroxy-4-methylselenobutanoic acid induces additional tissue selenium
      enrichment in broiler chickens compared with other selenium sources.
AB  - Two experiments were conducted in broiler chickens to compare the effect of
      different Se sources on Se tissue enrichment: sodium selenite (SS), seleno-yeast
      (SY), and a new organic Se source (SO) containing 2-hydroxy-4
      methylselenobutanoic acid (HMSeBA) as an active substance. For each experiment,
      treatments differed only in source or dose of Se additive. Relative efficiency
      was compared by plasma and tissue [muscle (pectoralis major) and liver] total Se
      concentrations. The first experiment compared Se sources (SS, SY, and SO) at
      different concentrations (mg of Se/kg of feed; SS-0.3; SY-0.1 and -0.3; SO-0.1
      and -0.3; and a negative control, 0) in broilers between 0 and 42 d of age.
      Plasma, liver, and muscle Se concentrations were improved by all Se sources at
      both d 21 and 42 compared with the negative control group. Between Se sources,
      minor differences were observed for plasma and liver results, whereas a
      significant dose effect was observed from 0.1 to 0.3 mg of Se/kg of feed (P <
      0.05) for each source. Muscle Se concentrations were improved such as SO > SY >
      SS (P < 0.05). Moreover, the relative muscle Se enrichment comparison, using
      linear regression slope ratio, indicated an average of 1.48-fold (95% CI 1.38,
      1.58) higher Se deposition in muscle for SO compared with SY. In the second
      experiment, excessive dietary doses of 5 mg of Se/kg of feed from SS and SO
      showed a lower deleterious effect of SO on BW and feed intake in comparison with
      standard Se doses (P < 0.05). Seleno amino acid measurements conducted on
      different tissues of animals fed SO at 0.5 mg/kg of feed showed that HMSeBA is
      fully converted into selenomethionine and selenocysteine. These results of both
      experiments demonstrate the higher relative bioavailability of SO compared with
      SS and SY as determined through tissue Se enrichment. 

PMID- 24570428
TI  - Xylanase supplementation of a wheat-based diet improved nutrient digestion and
      mRNA expression of intestinal nutrient transporters in broiler chickens infected
      with Clostridium perfringens.
AB  - Necrotic enteritis caused by Clostridium perfringens has become prevalent in the
      European Union due to the withdrawal of antibiotics in poultry feed. In an
      experiment with a 2 * 2 factorial arrangement, 336 one-day-old male broiler
      chicks (Ross 308) were assigned to 4 groups with or without C. perfringens
      challenge and fed wheat-based diets supplemented with or without xylanase at
      5,500 U/kg of diet. The study aimed to investigate effects of xylanase addition
      on growth performance as well as nutrient digestion and absorption of C.
      perfringens-infected broilers. Before challenge (d 0-14), xylanase-supplemented
      birds had greater ADG and lower feed conversion ratio (FCR; P < 0.05). During
      infection (d 14-21), challenge tended to decrease ADG (P = 0.063) and
      significantly increased FCR (P < 0.05), whereas xylanase addition greatly reduced
      FCR (P < 0.05). Clostridium perfringens infection decreased AME values and
      apparent ileal digestibility of DM of diets (P < 0.05). Xylanase supplementation
      increased AME values regardless of infection and apparent ileal digestibility of
      CP in challenged birds (P < 0.05). Activities of duodenal alpha-amylase and
      chymotrypsin and pancreatic trypsin were decreased by C. perfringens infection (P
      < 0.05). Xylanase supplementation elevated pancreatic chymotrypsin activity and
      reduced duodenal alpha-amylase and trypsin activities (P < 0.05). It also
      decreased jejunal alpha-amylase activity and increased pancreatic alpha-amylase
      as well as jejunal sucrase activities in uninfected birds (P < 0.05). The
      duodenal mRNA expression of sodium glucose cotransporter 1 (SGLT1), H(+)
      dependent peptide transporter 1 (PepT1), and liver fatty acid-binding protein (L
      FABP) were downregulated (P < 0.05), but ileal SGLT1 gene expression was
      increased by infection (P < 0.05). Xylanase addition upregulated expression of
      jejunal SGLT1, PepT1, and L-FABP genes as well as ileal PepT1 and L-FABP genes in
      challenged broilers (P < 0.05). In conclusion, xylanase supplementation of wheat
      based diets improved FCR and AME in birds irrespective of C. perfringens
      infection and elevated apparent ileal digestibility of CP and mRNA expression of
      nutrient transporters in challenged birds. 

PMID- 24570429
TI  - Productive performance, eggshell quality, and eggshell ultrastructure of laying
      hens fed diets supplemented with organic trace minerals.
AB  - This study was carried out with the purpose of evaluating the effect of
      supplementing hens' diets with trace minerals from inorganic or organic sources
      on the productive performance, eggshell quality, and eggshell ultrastructure of
      laying hens. Three hundred sixty Hy-Line W36 laying hens between 47 to 62 wk of
      age were used and distributed in a completely randomized experimental design with
      9 treatments, 5 replicates, and 8 birds for each experimental unit. The
      treatments consisted of a control diet without supplementation of the trace
      minerals Mn, Zn, and Cu; 4 supplementation levels of these trace minerals from an
      inorganic source; and the same levels of supplementation from an organic source
      (proteinates). The supplementation levels in milligrams per kilogram for Mn, Zn,
      and Cu, were, respectively, 35-30-05, 65-60-10, 95-90-15, and 125-120-20. There
      was no effect of supplementation of trace minerals on the rate of posture, feed
      intake, feed conversion, specific weight, and Haugh unit of eggs. However, there
      was a quadratic effect (P < 0.05) of the levels of trace mineral supplementation
      on average egg weight and egg mass; the results did not differ regarding the
      source used. The increase in the levels of supplementation of Mn, Zn, and Cu
      provided a linear increase (P < 0.05) in the breaking strength and the percentage
      of eggshell. There was a linear decrease (P < 0.05) in the egg loss and the
      number of mammillary buttons in the shell. The best results were obtained using
      diets supplemented with trace minerals from an organic source because these diets
      provided lower egg loss, higher thickness, and increased strength of the shell.
      Structurally, organic Mn, Zn, and Cu provided higher thickness of the palisade
      layer and lower mammillary density. The trace mineral supplementation improved
      the structural characteristics and the quality of the eggshells. 

PMID- 24570430
TI  - Activation of mammalian target of rapamycin signaling in skeletal muscle of
      neonatal chicks: effects of dietary leucine and age.
AB  - The mammalian target of rapamycin (mTOR) signaling pathway is necessary for
      cellular protein synthesis regulation. Leucine was reported to stimulate muscle
      protein synthesis in mammalian embryos and neonates, but in higher animals
      (chickens) the effect of dietary leucine on mTOR signaling is unknown. Thus, we
      investigated the effects of dietary leucine and age on mRNA expression and
      phosphorylation of mTOR as well as its downstream targets, ribosomal protein S6
      kinase (S6K1) and eukaryotic initiation factor 4E binding protein 1 (4E-BP1) in
      chick pectoral muscles. One hundred eighty newly hatched male chicks were
      randomly assigned to 1 of 3 dietary leucine treatment groups (1.43, 1.73, and
      2.03% leucine) for 14 d, respectively. Each treatment group consisted of 6 cages
      with 10 chicks each. On d 3, 7, and 14, plasma insulin and leucine were measured
      and target gene expression and phosphorylation was assessed. Dietary leucine
      influenced plasma leucine but not insulin, and plasma leucine and insulin
      declined with chick age. The mTOR, S6K1, and 4E-BP1 mRNA expression and
      phosphorylation within chick pectoral muscles were upregulated with increased
      dietary leucine but downregulated with increased chick age. Thus, high dietary
      leucine activates target of rapamycin signaling pathways in skeletal muscle of
      neonatal chicks to stimulate muscle protein synthesis, and this pathway is
      attenuated with aging. 

PMID- 24570431
TI  - Performance, serum biochemical responses, and gene expression of intestinal
      folate transporters of young and older laying hens in response to dietary folic
      acid supplementation and challenge with Escherichia coli lipopolysaccharide.
AB  - The present study was conducted to investigate the effects of dietary folic acid
      (FA) supplementation on performance, serum biochemical indices, and mRNA
      abundance of intestinal folate transporters in young and older laying hens after
      acute lipopolysaccharide (LPS) challenge. Two experiments were conducted
      separately involving 48 Shaver White young laying hens (24 wk of age) in
      experiment 1 and 48 Shaver White older laying hens (58 wk of age) in experiment
      2. Birds were fed 2 diets in a complete randomized design. The diets were wheat
      soybean meal based, with or without supplemental 4 mg of FA/kg of diet. Birds
      were fed for 8 wk, during which time feed consumption and egg production were
      monitored. At the end of each feeding experiment, 6 hens from each dietary
      treatment were injected intravenously with 8 mg/kg of BW of either Escherichia
      coli LPS or sterile saline. Four hours after injection, blood and intestinal
      samples were collected for further analysis. Compared with the control, dietary
      FA supplementation increased egg weight and egg mass and decreased serum glucose
      levels in the young laying hens, and reduced serum uric acid in the older laying
      hens (P < 0.05). Relative to saline injection, plasma homocysteine, serum
      calcium, and phosphorus levels were found to be lower in both young and older
      laying hens after LPS challenge (P < 0.05). Other serum biochemical variables and
      the mRNA expression of 2 folate transport genes in the small and large intestine
      were differentially affected by LPS challenge, and some of those responses varied
      with the age of the birds. Additionally, interactions between diet and LPS
      challenge were specifically found in the older laying hens. In summary, in
      addition to improving production performance, there were effects of dietary FA
      supplementation and its interaction with LPS challenge on biochemical
      constituents, and age played a role in the development of responses to diet and
      bacterial LPS infections. 

PMID- 24570432
TI  - Effects of natural blend of essential oil on growth performance, blood
      biochemistry, cecal morphology, and carcass quality of broiler chickens.
AB  - The study evaluated the effect of a novel commercial preparation of natural blend
      of essential oils from basil, caraway, laurel, lemon, oregano, sage, tea, and
      thyme (Tecnaroma Herbal Mix PL) on growth performance, blood biochemistry, cecal
      morphology, and carcass quality of broilers. Six nutritionally adequate wheat and
      soybean-based diets were generated by the addition of Tecnaroma Herbal Mix PL at
      0, 100, 200, 300, 400, and 500 g/t of feed. The diets were fed as crumbs in the
      starter phase (d 0-10) and as pellets during the grower (d 10-24) and finisher (d
      24-42) phases. Nine hundred sixty 1-d-old chicks were allocated to the 6 dietary
      treatments each having 8 replicate pens with 20 birds per pen. The data obtained
      were analyzed using ANOVA with a P < 0.05 level of significance. Birds fed diets
      supplemented with Tecnaroma Herbal Mix PL had significantly heavier BW and higher
      (P < 0.05) weight gain and had improved (P < 0.05) feed to gain ratio compared
      with the control group during grower phase and overall performance. The blood
      biochemistry results showed no differences (P > 0.05) between treatments. The
      carcass weight, breast weight, and relative percentage of breast meat increased
      (P < 0.05) when diets were supplemented with Tecnaroma Herbal Mix PL compared
      with that from birds fed the control diet. The inclusion level of 300 g of
      Tecnaroma Herbal Mix PL/t of feed was optimum for enhancing breast meat yield and
      nutrient utilization as indicated by increased (P < 0.05) cecal villus surface
      area. 

PMID- 24570433
TI  - Decorin-induced proliferation of avian myoblasts involves the myostatin/Smad
      signaling pathway.
AB  - Decorin, a small leucine-rich proteoglycan as a component of the extracellular
      matrix, plays an important role in the skeletal muscle development. It has been
      reported that decorin promoted proliferation and differentiation of muscle cells
      by restraining myostatin activity in rodents. However, the effects and mechanisms
      of decorin on avian myoblast proliferation are not understood clearly. Thus, in
      our research, decorin overexpressing and knocking-down quail myoblast-7 (QM7)
      myoblasts were established to explore the effects of decorin on avian myoblast
      proliferation by flow cytometry. The results showed that overexpression of
      decorin enhanced the proliferation of QM7 myoblasts, which was accompanied by the
      upregulation of follistatin and primary muscle regulatory factors (i.e., myogenic
      factor 5, myogenic factor 1, myogenin), and downregulation of myostatin
      expression, as well as the decreased phosphorylation level of SMAD family member
      3 (Smad3). In line with expectations, decorin RNAi displayed an opposite effect
      on the proliferation and gene expression pattern of QM7 cells. In conclusion, our
      in vitro studies suggested the decorin-mediated myostatin/Smad signaling pathway
      might be involved in the regulation of avian myoblast proliferation. 

PMID- 24570434
TI  - Expression profiles of muscle genes in postnatal skeletal muscle in lines of
      chickens divergently selected for high and low body weight.
AB  - Long-term genetic selection for BW has generated high weight select (HWS) and low
      weight select (LWS) lines of chickens. These lines show an approximate 10-fold
      difference in BW at selection age (d 56). The objective of this study was to
      profile the expression of master regulators of early lineage specification (Pax3,
      Pax7) and myogenic regulatory factors (Myf5, MyoD1, MyoG, and Mrf4) on day of
      hatch and d 7, 28, and 56 in pectoralis major and gastrocnemius muscles. There
      was a line * age interaction for expression of all 6 genes in both muscles. In
      pectoralis major muscle, Pax3, MyoD1, and Mrf4 showed greater expression in LWS
      than HWS at day of hatch, whereas all 6 genes showed greater expression in HWS
      than LWS at d 28. In gastrocnemius muscle, Pax3, Myf5, MyoD1, and MyoG showed
      greater expression in LWS than HWS at day of hatch, whereas Pax7, Myf5, MyoD1,
      and Mrf4 showed greater expression in HWS than LWS at d 28. At day of hatch there
      was no difference in fiber number in gastrocnemius muscle between HWS and LWS;
      however, HWS had greater fiber diameter than LWS. These results indicate that in
      LWS there is enhanced expression of genes that are necessary for proliferation of
      progenitor muscle cells and muscle cell differentiation at day of hatch compared
      with HWS, but by d 28 these genes are expressed greater in HWS than LWS. Thus,
      long-term selection for growth has altered the pattern of muscle gene expression.

PMID- 24570435
TI  - Effects of the commercial in ovo injection of 25-hydroxycholecalciferol on
      broiler posthatch performance and carcass characteristics.
AB  - In ovo injection of 25-hydroxycholecalciferol [25(OH)D3] has been shown to
      improve hatchability of injected broiler eggs. Effects of the in ovo injection of
      commercial diluent containing various levels of 25(OH)D3 on broiler posthatch
      performance and carcass characteristics were investigated in 2 trials. On each of
      10 tray levels of a single-stage incubator, all treatment groups were randomly
      represented with each containing 21 and 40 eggs in trials 1 and 2, respectively.
      Treatments included noninjected and diluent-injected (100 uL commercial diluent
      injected) controls, and those that received 0.15, 0.30, 0.60, or 1.20 ug of
      25(OH)D3 in trial 1 and 0.20, 0.60, 1.80, or 5.4 ug of 25(OH)D3 in trial 2, in
      100 uL of commercial diluent using a commercial multi-egg injector on d 18 of
      incubation. On d 21 of incubation, chicks from each treatment replicate group
      were placed in corresponding floor pens. Feed intake, BW gain, and feed
      conversion were determined for the weekly and cumulative 0 to 21 d age intervals
      in trial 1 and for the weekly and cumulative 0 to 48 d age intervals in trial 2.
      In trial 2, 2 birds from each sex were selected from each treatment replicate
      group for determination of processing carcass characteristics on d 49 posthatch.
      Feed intake in the 0 to 7, 7 to 14, and 14 to 21 d age intervals and BW gain in
      the 0 to 7 and 14 to 21 d age intervals were affected by treatment in trial 2.
      The in ovo injection of up to 1.20 and 0.60 ug of 25(OH)D3 in trials 1 and 2,
      respectively, did not affect the BW gain of birds during the 0 to 7, 7 to 14, and
      14 to 21 d age intervals compared with the noninjected and diluent-injected
      control groups. It was concluded that the in ovo injection of up to 1.20 ug of
      25(OH)D3 into the amnion has no detrimental effect on the overall posthatch
      performance of broilers. 

PMID- 24570436
TI  - The effect of nutritional status and muscle fiber type on myogenic satellite cell
      fate and apoptosis.
AB  - Satellite cells (SC) are multipotential stem cells that can be induced by
      nutrition to alter their cellular developmental fate, which may vary depending on
      their fiber type origin. The objective of the current study was to determine the
      effect of restricting protein synthesis on inducing adipogenic
      transdifferentiation and apoptosis of SC originating from fibers of the fast
      glycolytic pectoralis major (p. major) and fast oxidative and glycolytic biceps
      femoris (b. femoris) muscles of the chicken. The availability of the essential
      sulfur amino acids Met and Cys was restricted to regulate protein synthesis
      during SC proliferation and differentiation. The SC were cultured and treated
      with 1 of 6 Met/Cys concentrations: 60/192, 30/96 (control), 7.5/24, 3/9.6,
      1/3.2, or 0/0 mg/L. Reductions in Met/Cys concentrations from the control level
      resulted in increased lipid staining and expression of the adipogenic marker
      genes peroxisome proliferator-activated receptor gamma and stearoyl-CoA
      desaturase during differentiation in the p. major SC. Although b. femoris SC had
      increased lipid staining at lower Met/Cys concentrations, there was no increase
      in expression of either adipogenic gene. For both muscle types, SC Met/Cys,
      concentration above the control increased the expression of peroxisome
      proliferator-activated receptor gamma and stearoyl-CoA desaturase during
      differentiation. As Met/Cys concentration was decreased during proliferation, a
      dose-dependent decline in all apoptotic cells occurred except for early apoptotic
      cells in the p. major, which had no treatment effect (P < 0.05). During
      differentiation, decreasing Met/Cys concentration caused an increase in early
      apoptotic cells in both fiber types and no effect on late apoptotic cells except
      for an increase in the p. major 7.5/24 mg/L of Met/Cys treatment. In general, the
      viability of the SC was unaffected by the Met/Cys concentration except during
      proliferation in the p. major 0/0 mg/L of Met/Cys treatment, which increased SC
      viability. These data demonstrate the effect of nutrition on SC
      transdifferentiation to an adipogenic lineage and apoptosis, and the effect of
      fiber type on this response in an in vitro context. 

PMID- 24570437
TI  - The effect of nutritional status and myogenic satellite cell age on turkey
      satellite cell proliferation, differentiation, and expression of myogenic
      transcriptional regulatory factors and heparan sulfate proteoglycans syndecan-4
      and glypican-1.
AB  - Posthatch satellite cell mitotic activity is a critical component of muscle
      development and growth. Satellite cells are myogenic stem cells that can be
      induced by nutrition to follow other cellular developmental pathways, and whose
      mitotic activity declines with age. The objective of the current study was to
      determine the effect of restricting protein synthesis on the proliferation and
      differentiation, expression of myogenic transcriptional regulatory factors
      myogenic determination factor 1, myogenin, and myogenic regulatory factor 4, and
      expression of the heparan sulfate proteoglycans syndecan-4 and glypican-1 in
      satellite cells isolated from 1-d-, 7-wk-, and 16-wk-old turkey pectoralis major
      muscle (1 d, 7 wk, and 16 wk cells, respectively) by using variable
      concentrations of Met and Cys. Four Met concentrations-30 (control), 7.5, 3, or 0
      mg/L with 3.2 mg/L of Cys per 1 mg/L of Met-were used for culture of satellite
      cells to determine the effect of nutrition and age on satellite cell behavior
      during proliferation and differentiation. Proliferation was reduced by lower Met
      and Cys concentrations in all ages at 96 h of proliferation. Differentiation was
      increased in the 1 d Met-restricted cells, whereas the 7 wk cells treated with 3
      mg/L of Met had decreased differentiation. Reduced Met and Cys levels from the
      control did not significantly affect the 16 wk cells at 72 h of differentiation.
      However, medium with no Met or Cys suppressed differentiation at all ages. The
      expression of myogenic determination factor 1, myogenin, myogenic regulatory
      factor 4, syndecan-4, and glypican-1 was differentially affected by age and Met
      or Cys treatment. These data demonstrate the age-specific manner in which turkey
      pectoralis major muscle satellite cells respond to nutritional availability and
      the importance of defining optimal nutrition to maximize satellite cell
      proliferation and differentiation for subsequent muscle mass accretion. 

PMID- 24570438
TI  - Quality attributes in breast muscle from broilers of an Arkansas randombred line
      varying in growth rate.
AB  - The physico-chemical quality attributes of meat from broilers with significant
      differences in growth rate were investigated in this study. Two chicken
      populations from a random mating broiler control population were established as a
      slow-growing subpopulation (SG) with an average growth rate of 229 g/wk and a
      fast-growing subpopulation (FG) with an average growth rate of 319 g/wk. The
      initial pH at 15 min and final pH after 24 h were higher (P < 0.05) in breast
      muscle from FG than muscle from the SG population. Muscle from the SG had higher
      (P < 0.05) L* and b* of 57.0 and 11.2, compared with L* and b* of 55.8 and 10.5
      from the FG. Although no difference in a* was observed, hue angle was different
      (P < 0.05) at 52.7 and 50.4 in FG and SG populations, respectively. Water-holding
      capacity was 25 to 27% and not different between the populations, but 5-d drip
      loss at 8.48% was higher (P < 0.05) in the muscle from the SG compared with the
      FG at 6.44%. Cook yield was higher (P < 0.05) in the FG muscle at 86.92% compared
      with the SG muscle at 85.96%. There was a positive correlation of +0.20 between
      pH difference and drip loss only in the FG. Significantly higher (P < 0.05) cook
      yields were observed in muscle from FG than SG chickens. The lower weight, higher
      L* value, and lower initial and final pH values in the SG population, coupled
      with higher drip loss and lower cook yield, likely result from differences in
      growth rate. 

PMID- 24570439
TI  - The effect of carbon dioxide on the shelf life of ready-to-eat shredded chicken
      breast stored under refrigeration.
AB  - The objective of the present study was to determine the shelf life of ready-to
      eat cooked chicken breast fillets (shredded) stored in atmospheres that were
      modified with different concentrations of CO2 and to establish a relationship
      between the concentration of this gas and bacterial growth. The samples were
      divided into 7 groups with different packaging conditions: aerobiosis, vacuum,
      and 10, 30, 50, 70, and 90% CO2 (with the remaining volume filled with N2). All
      of the samples were stored at 4 +/- 2 degrees C for 28 d. During this period, pH
      tests and counts of aerobic heterotrophic mesophyll bacteria (AHMB), aerobic
      heterotrophic psychotropic bacteria (AHPB), Enterobacteriaceae, and lactic acid
      bacteria (LAB) were performed, and the gas compositions of the packaging
      atmospheres were verified. The pH of the aerobic packages increased during
      storage. However, the other treatments resulted in the opposite trend, with the
      CO2 concentration decreasing over the first 24 h and then remaining constant
      until the end of experiment. A gradual increase in the AHMB, AHPB,
      Enterobacteriaceae, and LAB counts was observed during storage; this increase was
      faster in the meat that was packed under aerobiosis conditions than in the other
      treatments. The treatments with a CO2 concentration above 10% exhibited lower
      Enterobacteriaceae growth, whereas LAB growth was discrete in all of the
      treatments, independent of the CO2 concentration. The shelf life of the samples
      packed with 90% CO2 was 28 d. Based on the AHMB and AHPB counts, the shelf life
      was 3 times longer than for the samples packed under aerobiosis conditions (9 d).
      The increased package CO2 concentration caused a reduction in the growth rate of
      the examined bacteria (r = 0.99), and treatment with 90% CO2 appears promising as
      a method with which to increase the product's shelf life. 

PMID- 24570440
TI  - Inhibitory effect of chlorine and ultraviolet radiation on growth of Listeria
      monocytogenes in chicken breast and development of predictive growth models.
AB  - The inhibitory effect of chlorine (50, 100, and 200 mg/kg) was investigated with
      and without UV radiation (300 mW.s/cm(2)) for the growth of Listeria
      monocytogenes in chicken breast meat. Using a polynomial model, predictive growth
      models were also developed as a function of chlorine concentration, UV exposure,
      and storage temperature (4, 10, and 15 degrees C). A maximum L. monocytogenes
      reduction (0.8 log cfu, cfu/g) was obtained when combining chlorine at 200 mg/kg
      and UV at 300 mW.s/cm(2), and a maximum synergistic effect (0.4 log cfu/g) was
      observed when using chlorine at 100 mg/kg and UV at 300 mW.s/cm(2). Primary
      models developed for specific growth rate and lag time showed a good fitness
      (R(2) > 0.91), as determined by the reparameterized Gompertz equation. Secondary
      polynomial models were obtained using nonlinear regression analysis. The
      developed models were validated with mean square error, bias factor, and accuracy
      factor, which were 0.0003, 0.96, and 1.11, respectively, for specific growth rate
      and 7.69, 0.99, and 1.04, respectively, for lag time. The treatment of chlorine
      and UV did not change the color and texture of chicken breast after 7 d of
      storage at 4 degrees C. As a result, the combination of chlorine at 100 mg/kg and
      UV at 300 mW.s/cm(2) appears to an effective method into inhibit L. monocytogenes
      growth in broiler carcasses with no negative effects on color and textural
      quality. Based on the validation results, the predictive models can be used to
      accurately predict L. monocytogenes growth in chicken breast. 

PMID- 24570441
TI  - The evaluation of combined chemical and physical treatments on the reduction of
      resident microorganisms and Salmonella Typhimurium attached to chicken skin.
AB  - This study was conducted to evaluate the efficacy of sodium hypochlorite (NaOCl,
      0-200 mg/kg), thiamine dilauryl sulfate (TDS, 1,000 mg/kg), and ultrasound (37
      kHz, 380 W) on reducing Salmonella Typhimurim, mesophilic aerobic bacteria (MAB),
      and coliforms on chicken skin. Chemical and physical treatments were applied for
      5 min either singly or jointly, and Salmonella previously inoculated on chicken
      skin were quantitatively assessed using brilliant green agar, and the populations
      of MAB and coliforms in the native flora were enumerated using plate count agar
      and violet red bile agar, respectively. In the evaluation of bacterial
      attachment/detachment, chicken skin was quantitatively assessed for loosely,
      intermediately, and tightly attached bacteria. The treatment effects on bacteria
      detachment were also visualized using field emission scanning electron
      microscopy. In addition, color and textural properties of the skin after
      treatments were evaluated using a color difference meter and texture analyzer.
      Antimicrobial activity of NaOCl increased as the NaOCl concentration was
      increased, especially for loosely attached cells. The combination of 200 mg/kg
      NaOCl and ultrasound (NaOCl/ultrasound) significant reduced loosely,
      intermediately, and tightly attached bacteria populations by 0.75 to 0.47, 0.43
      to 0.41, and 0.83 to 0.54 log cfu/g for MAB, coliforms, and Salmonella
      Typhimurium, respectively. However, the combination of NaOCl and TDS (NaOCl/TDS)
      did not sufficiently reduce those cells on chicken skins, except for loosely
      attached MAB and coliforms. The NaOCl/ultrasound combination produced a higher
      reduction in numbers of inoculated and native bacteria flora than any single
      application, with no negative effect on skin color or texture. Generally, the
      loosely attached bacteria were less resistant to the chemical and physical
      treatments than the intermediately and tightly attached bacteria in chicken skin,
      presumably due to their location in deeper skin layer and crevices. Further
      research is needed to investigate how the intermediately and tightly attached
      microorganisms can be effectively eliminated from chicken skin. 

PMID- 24570442
TI  - Bacteriophage-induced reduction in Salmonella Enteritidis counts in the crop of
      broiler chickens undergoing preslaughter feed withdrawal.
AB  - Salmonella food poisoning is a public health problem. Feed withdrawal from
      broiler chickens before slaughter can favor the multiplication of Salmonella in
      the cecum and crop of contaminated animals and subsequently lead to contamination
      of carcasses in the processing plant. In the present study, a cocktail of lytic
      bacteriophages isolated from sewage water was orally administered to 45-d-old
      broiler chickens 1 h after they received an oral dose of 10(7) cfu/mL Salmonella
      enterica subspecies enterica serotype Enteritidis. Immediately after phage
      administration and 30 min, 1, 3, 6, and 12 h thereafter, groups of chicken were
      killed. Ceca and crops were analyzed for the presence of Salmonella. At 3 h
      posttreatment, there were 10(3) cfu/g and 10(1) cfu/g of cecal and crop
      suspension, respectively. At 6 h after treatment, the number of Salmonella was
      10(3) cfu/g in the cecal suspension, but below the detection limit in the crops.
      Our results suggest that bacteriophage therapy may be able to reduce the
      contamination of chicken carcasses by reducing the preslaughter load of
      Salmonella in the birds. 

PMID- 24570443
TI  - Computational modeling and preliminary iroN, fepA, and cirA gene expression in
      Salmonella Enteritidis under iron-deficiency-induced conditions.
AB  - Salmonellosis outbreaks in Europe, the United States, and Latin America have been
      associated with contaminated food derivatives including meat from the poultry
      industry. Salmonella grown under iron-limiting conditions has the capability to
      increase concentration of several iron-regulated outer-membrane proteins to
      augment the acquisition of the metal. These proteins have been proved to have
      immunogenic properties. Our aim was to increase the relative expression of iroN,
      fepA, and cirA in Salmonella Enteritidis domestic strain. Furthermore, we
      proposed a 3-dimensional structure model for each protein to predict and locate
      antigenic peptides. Our eventual objective is to produce an effective vaccine
      against regional avian salmonellosis. Two simple factorial designs were carried
      out to discriminate between 2 nitrogen sources and determine chelating-agent
      addition timing to augment relative gene expression. Two antigenic peptides
      located at the external face of each protein and 2 typical domains of iron
      regulated outer-membrane proteins, plug and TonB-dep-Rec, were identified from
      the 3-dimensional models. Tryptone was selected as the best nitrogen source based
      on growth rate (MUx = 0.36 h(-1)) and biomass productivity (Px = 0.9 g*h(-1)*L(
      1)) as determined by a general factorial design. Optimum timing for chelating
      agent addition was in the middle of the log phase, which allowed relative
      expressions at 4 h of culture. Increase in iroN, fepA, and cirA relative
      expression was favored by the length of log phase and the addition of chelating
      agent, which decreased chelating toxicity and enhanced cell growth rate. 

PMID- 24570444
TI  - The greenhouse emissions footprint of free-range eggs.
AB  - Eggs are an increasingly significant source of protein for human consumption, and
      the global poultry industry is the single fastest-growing livestock sector. In
      the context of international concern for food security and feeding an
      increasingly affluent human population, the contribution to global greenhouse-gas
      (GHG) emissions from animal protein production is of critical interest. We
      calculated the GHG emissions footprint for the fastest-growing sector of the UK
      egg market: free-range production in small commercial units on mixed farms.
      Emissions are calculated to current Intergovernmental Panel on Climate Change and
      UK standards (PAS2050): including direct, indirect, and embodied emissions from
      cradle to farm gate compatible with a full product life-cycle assessment. We
      present a methodology for the allocation of emissions between ruminant and
      poultry enterprises on mixed farms. Greenhouse gas emissions averaged a global
      warming potential of 2.2 kg of CO2e/dozen eggs, or 1.6 kg of CO2equivalent (e)/kg
      (assuming average egg weight of 60 g). One kilogram of protein from free-range
      eggs produces 0.2 kg of CO2e, lower than the emissions from white or red meat
      (based on both kg of meat and kg of protein). Of these emissions, 63% represent
      embodied carbon in poultry feed. A detailed GHG emissions footprint represents a
      baseline for comparison with other egg production systems and sources of protein
      for human consumption. Eggs represent a relatively low-carbon supply of animal
      protein, but their production is heavily dependent on cereals and soy, with
      associated high emissions from industrial nitrogen production, land-use change,
      and transport. Alternative sources of digestible protein for poultry diets are
      available, may be produced from waste processing, and would be an effective tool
      for reducing the industry's GHG emissions and dependence on imported raw
      materials. 

PMID- 24570445
TI  - Comparison of the environmental footprint of the egg industry in the United
      States in 1960 and 2010.
AB  - The US egg industry has evolved considerably over recent decades by incorporating
      new technologies and production practices. To date, there has been no
      comprehensive assessment of the resource demand and environmental effects of
      these changes. This study quantifies the environmental footprint of egg
      production supply chains in the United States for 2010 compared with 1960 using
      life cycle assessment. The analysis considers changes in both foreground (e.g.,
      hen production performance) and background (e.g., efficiencies of energy
      provision, fertilizer production, production of feed inputs, and transport modes)
      system variables. The results revealed that feed efficiency, feed composition,
      and manure management are the 3 primary factors that determine the environmental
      impacts of US egg production. Further research and improvements in these areas
      will aid in continual reduction of the environmental footprint of the US egg
      industry over time. Per kilogram of eggs produced, the environmental footprint
      for 2010 is 65% lower in acidifying emissions, 71% lower in eutrophying
      emissions, 71% lower in greenhouse gas emissions, and 31% lower in cumulative
      energy demand compared with 1960. Table egg production was 30% higher in 2010;
      however, the total environmental footprint was 54% lower in acidifying emissions,
      63% lower in eutrophying emissions, 63% lower in greenhouse gas emissions, and
      13% lower in cumulative energy demand compared with 1960. Reductions in the
      environmental footprint over the 50-yr interval considered can be attributed to
      the following: 27 to 30% due to improved efficiencies of background systems,
      which outweighed the declining energy return on energy invested for primary
      energy sources; 30 to 44% due to changes in feed composition; and 28 to 43% due
      to improved bird performance.

PMID- 24570446
TI  - The effects of welfare-enhancing system changes on the environmental impacts of
      broiler and egg production.
AB  - The environmental impacts of 2 alternative UK broiler production systems that aim
      to improve bird welfare (a lower stocking density indoor system and the same
      system combined with heat exchangers for ventilation air) were compared with the
      baseline standard indoor system of broiler production. Furthermore, the
      environmental impacts of egg production in the conventional battery cage system
      (banned in the European Union in 2012) and its replacement, the enriched colony
      cage system, were compared. All comparisons were based on data obtained from the
      UK poultry industry, and the life cycle assessment method from cradle to farm
      gate was applied in the analyses. The results show that the lower density system
      slightly increased the global warming potential (GWP) of broiler production (by
      2%), compared with the standard indoor system, due to increased heating
      requirements. However, when combined with the heat exchanger, the GWP was
      actually reduced by 3% when compared with the standard system. Both alternative
      systems for broilers resulted in a reduction in the eutrophication potential (by
      up to 8%) and acidification potential (by up to 10%). The results also showed
      that the colony cage system had 8% lower primary energy use and 3% lower GWP than
      the baseline cage system, due to better energy use efficiency and slightly
      improved productivity. There were only minor differences in the eutrophication
      and acidification potentials between different egg production systems. The
      results suggest that welfare-friendly changes in chicken systems can be achieved
      without a compromise in their environmental impacts. 

PMID- 24570447
TI  - Evaluation of linalool, a natural antimicrobial and insecticidal essential oil
      from basil: effects on poultry.
AB  - Linalool is a natural plant-product used in perfumes, cosmetics, and flavoring
      agents. Linalool has proven antimicrobial and insect-repellent properties, which
      indicate it might be useful for control of enteropathogens or insect pests in
      poultry production. However, there are no published reports that linalool may be
      safely administered to or tolerated by chickens. Linalool was added to the diets
      of day-of-hatch chicks, and they were fed linalool-supplemented diets for 3 wk.
      We studied the effects of linalool on serum chemistry, gross pathology, feed
      conversion, and relative liver weights. Linalool had a dramatic negative dose
      dependent effect on feed conversion at concentrations in the feed exceeding 2%
      linalool, but not on gross pathology. Liver weights were significantly increased
      in the 5% linalool-treated birds. There was a statistical effect on blood
      glucose, but this parameter remained below the cut-offs for elevated serum
      glucose, and the result is likely of no biological significance. Linalool caused
      serum aspartate aminotransferase (AST) levels to increase, but it did not
      increase serum gamma-glutamyl transferase levels. The linalool effect on AST was
      dose-dependent, but in linalool doses between 0.1 and 2% of the feed, AST was not
      elevated beyond normal parameters. Linalool at 2% or less may be safely added to
      chicken feed. We suggest future studies to evaluate the addition of linalool to
      the litter, where it may be used as an antimicrobial or an insect repellent or to
      produce a calming effect.

PMID- 24570448
TI  - Transportation stress and the incidence of exertional rhabdomyolysis in emus
      (Dromaius novaehollandiae).
AB  - Many emu farms are located in areas lacking processing facilities that can handle
      these birds. Thus, long-distance shipping of birds to an abattoir is necessary.
      Two experiments were conducted, wherein emus were transported in a modified horse
      trailer for 6 h to an abattoir. Changes in the indices of stress and metabolic
      homeostasis (hematology, serum biochemistry, enzymes, and body temperature and
      weight) were used to evaluate the physiological response to transport. The
      activities of enzymes alanine aminotransferase, aspartate aminotransferase, and
      creatine kinase increased significantly (P < 0.001) from pretransport to
      slaughter, indicating muscle cell wall damages. The body temperature of emus was
      significantly (P < 0.001) increased from 37.0 to 39.6 degrees C after transport
      in experiment 1 and from 37.2 to 38.9 degrees C in experiment 2. Transport
      resulted in significant weight loss in both experiments (P < 0.001; 2.1 +/- 0.2
      kg vs. 0.6 +/- 0.2 kg) and posttransport resting at lairage led to slight
      regaining (P < 0.01) of BW. Oral administration of supplements before and after
      transport was effective in protecting against muscle damage and faster recovery
      of BW losses during lairage. The clinical findings were suggestive of the
      incidence of exertional rhabdomyolysis and thus underlined the need for careful
      handling and improved transport conditions of emus.

PMID- 24570449
TI  - The effect of dietary alterations during rearing on growth, productivity, and
      behavior in broiler breeder females.
AB  - Parent stocks of meat birds are severely feed restricted to avoid obesity-related
      health and fertility problems. This restriction often leads to chronic hunger,
      accompanied by stereotypic behavior. Research based in the United Kingdom has
      shown that using diets containing fiber and appetite suppressants may relieve
      some of the symptoms of hunger. However, few data are available regarding North
      American-sourced ingredients or nondaily feeding regimens. This study
      investigated the effects of 2 alternative diets, in combination with 2 feeding
      frequencies on growth, productivity, and behavior in broiler breeders. Six
      dietary treatments were tested, each with 5 replicate pens of 12 or 13 birds.
      Control diets consisted of a commercial crumble, fed on a daily or skip-a-day
      (SAD) basis. Alternative diets included soybean hulls as a fiber source, and
      calcium propionate as an appetite suppressant of either a feed-grade or purified
      quality, fed on either a daily or SAD basis. Birds were weighed weekly and egg
      production was recorded daily. Video cameras were used to record behavior during
      and following the morning feeding bout every 2 wk from 11 to 28 wk. Data were
      analyzed with a mixed model ANOVA, with repeated measures. Diet, feeding
      frequency, time, or an interaction of the 3 had significant effects on all
      observed behavior during rearing. These differences appeared to diminish during
      lay, with most stereotypic behavior no longer present. Very little object pecking
      and aggression was observed during and immediately following feeding bouts;
      however, daily-fed control birds still displayed this behavior more often,
      especially during rearing (P = 0.015). During feeding bouts, SAD birds feather
      pecked (P = 0.003) and rested more (P = 0.0002) than daily-fed birds. Control
      birds feather pecked most often (P = 0.033) after feeding bouts. Overall, the
      feed-grade diet appeared most effective at reducing hunger-related behavior, and
      the control diet appeared the least effective. There was little conclusive
      evidence to show that daily feeding was more effective at reducing hunger.

PMID- 24570450
TI  - A survey of current ostrich handling and transport practices in North America
      with reference to ostrich welfare and transportation guidelines set up in other
      countries.
AB  - Appropriate management of an ostrich's exposure to stressors during preslaughter
      handling and transport practices can improve its well-being and product quality.
      Because of the lack of information about ostrich farming and transportation in
      North America and lack of developed Codes of Practice for ratite transport in
      Canada and the United States, the first objective of our research was to identify
      current preslaughter handling and transport practices of the ostrich industry in
      Canada and the United States, and to identify potential welfare issues based on
      the current practices. The second objective of this research was to review
      ostrich transport welfare standards and guidelines from Australia, European
      Union, New Zealand, and South Africa to investigate if those guidelines are
      applicable to Canadian and American ostrich production systems. Preliminary
      producer interviews, on-farm visits, and literature review information sources
      were used to design a producer questionnaire that was used to survey producers by
      Internet and mail surveying methods to identify existing ostrich transport norms
      in Canada and the United States. Based on the results of our producer survey and
      review of the transport standards and guidelines, we conclude that following
      factors are potential ostrich handling and transport welfare issues in Canada and
      the United States: lack of scientific information about welfare of ostriches
      during handling and transport; unfamiliarity of handlers and birds with handling
      and transport practices; not considering birds' social bounds, sex, behavior, and
      physical state in mixing them during handling and transport process; lack of an
      established specific maximum water and feed withdrawal duration for ostrich
      transport in Canada and the United States; lack of a specific vehicle designed
      for ratite transportation in Canada and the United States considering different
      physical body characteristics of ostriches compared with other species; exposure
      of birds to natural light during transport inside the trailer; overcrowding; and
      long transportation in Canada and the United States. Results of this research
      will contribute toward developing Codes of Practice for preslaughter handling,
      transportation, and slaughter of ostriches in Canada and the United States. 

PMID- 24570452
TI  - Comparison of microsatellite variations between Red Junglefowl and a commercial
      chicken gene pool.
AB  - It is assumed that Red Junglefowl (Gallus gallus) is one of the main ancestors of
      domestic chickens (Gallus gallus domesticus). Differences in microsatellite
      polymorphisms between Red Junglefowl and modern commercial chickens, which are
      used for egg and meat production, have not been fully reported. A total of 361
      individuals from 1 Red Junglefowl population that has been maintained as a closed
      flock, 5 final cross-bred commercial layer populations (white-, tinted-, and
      brown-egg layers), and 2 final cross-bred commercial broiler populations were
      genotyped for 40 autosomal microsatellite loci. We compared microsatellite
      variations in Red Junglefowl with those in a commercial chicken gene pool. The
      contribution of each population to the genetic diversity was also estimated based
      on the molecular coancestry. In total, 302 distinct alleles were detected in 1
      Red Junglefowl and 7 commercial chicken populations, of which 31 alleles (10.3%)
      were unique to Red Junglefowl, most of which occurred at a high frequency. The
      genetic differentiation between Red Junglefowl and commercial chickens (pairwise
      FST) ranged from 0.32 to 0.47. According to the neighbor-joining tree based on
      the modified Cavalli-Sforza chord distances and the Bayesian clustering analysis,
      Red Junglefowl was genetically distant from the commercial chicken gene pool
      tested. In all of the populations analyzed, Red Junglefowl made the highest
      contribution to genetic diversity. These results suggest that Red Junglefowl has
      a distinct distribution of microsatellite alleles and that there is a high level
      of genetic divergence between Red Junglefowl and commercial chickens. 

PMID- 24570451
TI  - A quantitative trait locus for ascites on chromosome 9 in broiler chicken lines.
AB  - A genome-wide SNP survey was used to identify chromosomal regions that showed
      linkage disequilibrium with respect to ascites susceptibility and ventricular
      hypertrophy in an F2 cross between previously described ascites-resistant and 
      susceptible lines. Variable number tandem repeats were used to obtain genotype
      data to further characterize these regions. A region on chromosome 9 (12 to 13
      Mbp in 2011 assembly) shows association with ascites in the ascites lines and in
      several commercial broiler breeder lines with a significant sex effect. There are
      2 candidate genes, AGTR1 (an angiotensin II type 1 receptor) and UTS2D (urotensin
      2 domain containing), in this region that have been associated with hypertension
      and hypoxic response in mammals. 

PMID- 24570453
TI  - Effects of heat treatment of soy protein isolate on the growth performance and
      immune function of broiler chickens.
AB  - This study was conducted to evaluate the effects of oxidative modification of soy
      protein isolate (SPI) after exposure to heat on the growth performance and immune
      function of broilers. The SPI was heated in an oven at 100 degrees C for 1, 4,
      and 8 h, respectively, and resultant oxidative status was evaluated. A total of
      320 one-day-old Arbor Acres chickens were randomly divided into 4 treatment
      groups with 8 replicates of 10 birds, and fed diets supplemented with the native
      SPI or 1 of the 3 heat-treated SPI for 21 d. The results showed that heat
      exposure of SPI for 4 and 8 h caused an increase in protein carbonyl (P < 0.05),
      and a simultaneous decrease in sulfhydryl and free amine groups (P < 0.05)
      compared with native SPI. The BW of broilers fed diets supplemented with SPI
      heated for 8 h were significantly lower than that of broilers fed diets
      supplemented with native SPI (P < 0.05). Compared with native SPI, heat-treated
      SPI (heated for 8 h) diminished liver weight at 14 d (P = 0.01), spleen (P <
      0.01) and bursa (P < 0.05) weights at 21 d; and the content of IgG in serum and
      duodenal mucosa of broilers (at 14 d) was decreased when diets supplemented with
      heat-treated SPI (heated for 8 h; P < 0.01). No significant differences were
      observed in the mucosa secretory IgA contents of broilers among the treatment
      groups (P > 0.05). Compared with native SPI, a significant increases were
      observed in the content of adrenocorticotropic hormone and cortisol in serum of
      broilers fed the heat-treated SPI (heated for 8 h) at 21 d (P < 0.05); and the
      myeloperoxidase activities in serum (at 14 d) and mucosa of broilers were
      increased when diets supplemented with heat-treated SPI (heated for 8 h; P <
      0.05). The present study suggests that protein oxidation of SPI is induced by
      heating, and oxidized protein may negatively affect the immune function of
      broilers.

PMID- 24570454
TI  - Molecular epidemiological survey on quinolone resistance genotype and phenotype
      of Escherichia coli in septicemic broilers in Hebei, China.
AB  - In this study, the quinolone-resistant determining region (QRDR) of gyrA of
      Escherichia coli and plasmid-mediated quinolone resistance (PMQR) genes,
      qnr(qnrA, qnrB, and qnrS), and aac(6 ')-Ib-cr were detected, sequenced, and
      analyzed. In addition, antimicrobial susceptibility tests (using the Kirby-Bauer
      disc diffusion method) were performed for all 111 E. coli isolates from
      septicemic broilers in Hebei, China. The results show that the resistance rates
      were as follows: ofloxacin 99.10%, ciprofloxacin 93.69%, levofloxacin 91.89%,
      norfloxacin 90.09%, and gatifloxacin 76.58%. Of the PMQR genes examined, aac(6 ')
      Ib-cr (36.04%) was the most frequently identified gene in all isolates, followed
      by qnrS (8.11%), qnrB (0.90%), and qnrA (0%). Of the QRDR examined in the 40
      phenotypic quinolone-resistant isolates, compared with the gyrA(+) gene of E.
      coli K-12, 4 amino acid exchanges were found, namely Ser-83->Asp, Asp-87->Asn,
      Asp-87->Tyr, and Asp-87->Ala, and all 40 isolates had 1 or 2 exchanges in QRDR.
      It was concluded that quinolone-resistance in E. coli remains a serious problem
      in Hebei, China. Therefore, there is considerable local surveillance of quinolone
      resistance. Plasmid-mediated quinolone resistance of the qnr type remains rare in
      Hebei, China, and mutation in QRDR may be the main problem.

PMID- 24570456
TI  - Effects of dietary supplementation of quercetin on performance, egg quality,
      cecal microflora populations, and antioxidant status in laying hens.
AB  - Plant polyphenols, especially flavonoids, are of great interest due to their wide
      range of biological activities. Quercetin, a ubiquitous flavonoid, is known to
      have antioxidant and antibacterial effects. In this study, we investigated the
      effect of quercetin on performance, egg quality, cecal microflora populations,
      and antioxidant status in laying hens. Two hundred forty 28-wk-old Hessian laying
      hens, with an average laying rate of lay 85% at the start, were randomly allotted
      to 4 treatments and fed 1 of 4 diets (negative control, 0.2, 0.4, and 0.6 g of
      quercetin/kg of diet) for 8 wk. Layer performance responses, egg quality
      parameters, cecal microflora populations and antioxidant status were measured at
      the end of the experiment. Results showed that feed conversion decreased as the
      quercetin level increased. Laying rate had a quadratic correlation with the level
      of quercetin (P = 0.056) and was maximized by the supplementation level of 0.2
      g/kg of diet. However, no significant quercetin effect was observed on egg
      quality. Regression analysis showed that the population of total aerobes and
      coliforms decreased and the population of Bifidobacteria increased as the level
      of quercetin increased. Regression analysis also showed the activities of Cu-Zn
      superoxide dismutase increased as the level of quercetin increased (P < 0.05).
      Results of the study suggest that the appropriate level of supplementation is
      0.367 to 0.369 g of quercetin/kg of feed based on the improvement of laying rate
      (with 88.55 as maximum value) and feed conversion (with 2.0725 as minimum value).
      Our observations provided further evidence that dietary supplementation of
      quercetin improved performance by modulation of intestinal environment and liver
      superoxide dismutase content in laying hens. Quercetin has the potential as
      functional feed additive in animal production. 

PMID- 24570455
TI  - Evaluation of the respiratory route as a viable portal of entry for Salmonella in
      poultry via intratracheal challenge of Salmonella Enteritidis and Salmonella
      Typhimurium.
AB  - Experimental and epidemiological evidence suggests that primary infection of
      Salmonella is by the oral-fecal route for poultry. However, the airborne
      transmission of Salmonella and similar enteric zoonotic pathogens has been
      historically neglected. Increasing evidence of Salmonella bioaerosol generation
      in production facilities and studies suggesting the vulnerabilities of the avian
      respiratory architecture together have indicated the possibility of the
      respiratory system being a potential portal of entry for Salmonella in poultry.
      Presently, we evaluated this hypothesis through intratracheal (IT) administration
      of Salmonella Enteritidis and Salmonella Typhimurium, as separate challenges, in
      a total of 4 independent trials, followed by enumeration of cfu recovery in ceca
      cecal tonsils and recovery incidence in liver and spleen. In all trials, both
      Salmonella Enteritidis and Salmonella Typhimurium, challenged IT colonized cecae
      to a similar or greater extent than oral administration at identical challenge
      levels. In most trials, chickens cultured for cfu enumeration from IT-challenged
      chicks at same dose as orally challenged, resulted in an increase of 1.5 log
      higher Salmonella Enteritidis from ceca-cecal tonsils and a much lower dose IT of
      Salmonella Enteritidis could colonize ceca to the same extent than a higher oral
      challenge. This trend of increased cecal colonization due to IT challenge was
      observed with all trails involving week-old birds (experiment 2 and 3), which are
      widely considered to be more difficult to infect via the oral route. Liver-spleen
      incidence data showed 33% of liver and spleen samples to be positive for
      Salmonella Enteritidis administered IT (10(6) cfu/chick), compared with 0% when
      administered orally (experiment 2, trial 1). Collectively, these data suggest
      that the respiratory tract may be a largely overlooked portal of entry for
      Salmonella infections in chickens. 

PMID- 24570457
TI  - The effect of dietary calcium inclusion on broiler gastrointestinal pH:
      quantification and method optimization.
AB  - There is little consensus as to the most appropriate methodology for the
      measurement of gastrointestinal pH in chickens. An experiment was conducted to
      establish the optimum sampling method for the determination of broiler digesta pH
      in birds fed differing levels of dietary calcium. Ross 308 broilers (n = 60) were
      fed 1 of 2 experimental diets, one containing 0.8% monocalcium phosphate and 2%
      limestone and one containing 0.4% monocalcium phosphate and 1% limestone. Four
      factors were investigated to determine the most appropriate method of measuring
      broiler gastrointestinal digesta pH: removal from the tract, prolonged air
      exposure, altering the temperature of the assay, and controlling the water
      content of the digesta. The conditions were assessed at bird ages from 7 to 42 d
      posthatch. Dietary Ca content had no significant effect on in situ pH, but it
      contributed toward variance in ex situ pH of both gizzard and duodenum digesta.
      Digesta pH read higher when the digesta was removed from the tract, but the
      amount of time the digesta was exposed to air did not affect the reading. Digesta
      pH read higher when measured at room temperature than when measured at 41 degrees
      C; temperature made the strongest unique contribution to explaining variance in
      duodenum pH, and the second strongest contribution to explaining variance in
      gizzard pH, after diet. When water was added to the digesta, before pH
      determination, the pH of the digesta read higher (P < 0.001) than when measured
      in situ. The method that resulted in pH readings that were most representative of
      bird gastrointestinal environment was insertion of a pH probe directly into the
      gut lumen posteuthanasia, because measurement ex situ likely encourages
      dissociation of carbonic acid, the major buffer in the gastrointestinal tract,
      which causes pH to read to be higher than when measured in situ. This study shows
      that the method of pH measurement needs careful consideration to ensure the
      validity of the result.

PMID- 24570458
TI  - Effects of multistrain probiotics on growth performance, apparent ileal nutrient
      digestibility, blood characteristics, cecal microbial shedding, and excreta odor
      contents in broilers.
AB  - This experiment was conducted to investigate the efficacy of Lactobacillus
      acidophilus, Bacillus subtilis, and Clostridium butyricum supplementation in
      broilers. A total of 400 one-day-old mixed sex Ross 308 broilers with an initial
      average BW of 46 +/- 0.5 g were randomly allotted into 4 treatments with 5
      replicate pens per treatment and 20 broilers in each pen for 35 d. Dietary
      treatments were (1) an antibiotic-free diet (CON), (2) CON + 5 mg/kg of
      avilamycin, (3) CON + 1 * 10(5) cfu of multistrain probiotics/kg of diet (P1),
      and (4) CON + 2 * 10(5) cfu of multistrain probiotics/kg of diet (P2). Broilers
      fed the P1 and P2 diets had greater BW gain than broilers fed the CON diet during
      d 22 to 35 (P = 0.01) and overall (P = 0.02). Feed conversion ratios in P1 and P2
      were decreased (P = 0.03) compared with that in CON from d 22 to 35. Ileal
      digestibility of most essential amino acids, with the exception of His and Phe,
      were increased (P < 0.05) in P1 and P2 compared with CON. Serum IgA and IgM
      concentrations in P2 were higher (P < 0.05) than those in CON. The cecal
      Lactobacillus numbers were increased (P = 0.02), and the counts of Escherichia
      coli were decreased (P = 0.03) in P1 and P2 compared with CON. Dietary
      supplementation with multistrain probiotics decreased (P < 0.05) the excreta NH3
      content compared with the CON. In conclusion, dietary supplementation with
      multistrain probiotics improved broiler growth performance, ileal amino acids
      digestibility, and humoral immunity. Furthermore, the probiotics decreased the
      cecal numbers of E. coli and decreased the NH3 content of excreta. 

PMID- 24570459
TI  - Digestion of fat and fatty acids along the gastrointestinal tract of broiler
      chickens.
AB  - Two experiments were conducted. The first experiment investigated the digestion
      of fat and fatty acids (FA) from soybean oil and tallow along the
      gastrointestinal tract of broiler chickens. The second experiment was conducted
      to determine endogenous fat and FA losses and the FA profile of chicken bile. In
      experiment 1, 2-wk-old broilers were fed corn-soy diets supplemented with 50 g/kg
      of soybean oil or tallow for 7 d and digesta were collected from the duodenum,
      upper jejunum, upper ileum, and lower ileum. Apparent digestibility coefficients
      were calculated using the titanium marker ratio in diets, and digesta.
      Digestibility of fat was determined to be negative in the duodenum, indicating
      marked net secretion of fat into this segment. Fat was rapidly digested in the
      jejunum, with digestibility coefficients of 0.60 to 0.64 being determined at the
      end of the jejunum. The digestion of fat continued in the upper ileum. The
      apparent digestibility coefficient of fat determined at lower ileum in soybean
      oil diets was higher (P < 0.05) than that in tallow diets (0.82 vs. 0.74).
      Linoleic acid was digested throughout the intestinal tract, whereas the digestion
      of palmitic, stearic, and oleic acids started only in the jejunum. Measurements
      at the lower ileal level showed that the unsaturated FA (linoleic and oleic
      acids) were well digested (0.90 to 0.94), irrespective of the source of fat. In
      contrast, the digestibility of saturated FA (palmitic and stearic acids) was
      influenced (P < 0.05) by the fat source. Digestibility coefficients of palmitic
      and stearic acids at lower ileum were markedly higher (P < 0.05) in the diet
      containing soybean oil (0.77 to 0.85) compared with that containing tallow (0.58
      to 0.68). In experiment 2, ileal endogenous fat loss was determined to be 1,714
      mg/kg of DM intake. Endogenous fat was composed mainly of palmitic (75 g/kg),
      stearic (131 g/kg), oleic (73 g/kg), linoleic (133 g/kg), and arachidonic (60
      g/kg) acids. Fatty acid profile of endogenous fat was found to be remarkably
      similar to that of the bile, suggesting that the reabsorption of fat and FA from
      the bile was incomplete in growing broiler chickens.

PMID- 24570460
TI  - Manganese supplementation enhances the synthesis of glycosaminoglycan in eggshell
      membrane: a strategy to improve eggshell quality in laying hens.
AB  - This study investigated the effect of dietary Mn supplementation on eggshell
      quality, ultrastructure, glycosaminoglycan (GAG), and uronic acid content, and
      mRNA and protein expression of Galbeta1,3-glucuronosyltransferase (GlcAT-I). A
      total of 216 layers (Hy-Line Grey) at age of 50 wk were divided into 3 groups. In
      the first 8 wk of the 12-wk feeding trial, all groups were fed a basal diet that
      met all layer nutrient requirements except for Mn. In the last 4 wk, each group
      was fed 1 of 3 diets supplemented with Mn levels at 0, 25, or 100 mg Mn/kg.
      Dietary Mn deficiency did not affect the egg performance of layers. Dietary Mn
      supplementation significantly improved the breaking strength, thickness, and
      fracture toughness of eggshells (P < 0.05). In photographs of eggshell
      ultrastructure, the size of mammillary cones and cracks in the outer surface were
      decreased by dietary Mn supplementation. The contents of GAG and uronic acids in
      eggshell membrane were significantly increased by dietary Mn addition (P < 0.05).
      This result was further confirmed by increased mRNA expression and protein
      expression of GlcAT-I when Mn was added to the diet. This study suggests that
      dietary Mn supplementation can improve eggshell quality by enhancing the GAG and
      uronic acid synthesis in the eggshell glands, which can affect the ultrastructure
      of eggshells.

PMID- 24570462
TI  - Hydrolyzed porcine mucosa in broiler diets: effects on growth performance,
      nutrient retention, and histomorphology of the small intestine.
AB  - The effect of including hydrolyzed porcine mucosa sprayed into soybean meal (HPM)
      in the diet was studied in broilers. In experiment 1 (pen study), 1,080 one-day
      old chicks were used in a completely randomized design with 8 treatments arranged
      as a 4 * 2 factorial with 4 levels of HPM (0, 2.5, 5.0, and 7.5%) and 2 levels of
      Lys (1.23 and 1.38%). From d 1 to 22, HPM inclusion quadratically improved BW
      gain (BWG, P < 0.01) and feed conversion ratio (FCR, P < 0.01). From d 1 to 8,
      birds fed 1.38% Lys had higher BWG (P < 0.05) and better FCR (P < 0.05) than
      birds fed 1.23% Lys but only a trend (P < 0.08) for improved BWG was detected
      from d 1 to 22. From d 22 to 37, a period in which all birds received a common
      finisher diet, growth performance was not affected by the previous starter diet.
      In experiment 2 (battery study), birds were fed for 37 d the same diets used in
      the starter period of experiment 1. Broilers fed HPM had higher BWG (linear, P <
      0.05; Quadratic, P < 0.05) than birds fed control diet, and birds fed 1.38% Lys
      had higher BWG (P < 0.01) than birds fed 1.23% Lys. From d 1 to 22, BWG (P <
      0.05) and ADFI (P < 0.01) increased quadratically and FCR improved linearly (P <
      0.05) with HPM inclusion. Also in this period, BWG was higher at the higher Lys
      level (P < 0.01). Diet did not affect intestinal histomorphology of broilers on d
      8 or nutrient retention on d 22. We conclude that the inclusion of 2.5 to 5% HPM
      in the diet improved growth performance of broilers from d 1 to 22. An increase
      in Lys from 1.23 to 1.38% improved growth performance up to 15 d of age, but not
      thereafter. Diet did not affect villus histomorphology or nutrient retention of
      the small intestine. 

PMID- 24570463
TI  - Measurement of true ileal digestibility and total tract retention of phosphorus
      in corn and canola meal for broiler chickens.
AB  - The study reported herein was conducted to determine and compare the nonphytate
      P, digestible P, and retainable P contents of corn and canola meal for broiler
      chickens. Four semipurified diets were formulated from each of ingredient to
      contain graded concentrations of nonphytate P. The experiment was conducted as a
      randomized complete block design with 4 weight blocks of 8 cages each (6 birds
      per cage). A total of 192 broilers (Ross 308), 21 d old, were assigned to the 8
      test diets. Ileal digestibility and total tract retention coefficients of P were
      determined by the indicator and total collection methods, respectively, and
      linear regression method was used to determine the true P digestibility and true
      P retention coefficients. The apparent ileal digestibility of P in corn was
      influenced (quadratic, P < 0.05) by increasing dietary nonphytate P
      concentrations, whereas P retention was unaffected (P > 0.05). The apparent ileal
      P digestibility in broilers fed diets based on canola meal was similar (P > 0.05)
      at different P concentrations. Phosphorus retention in broilers fed diets based
      on canola meal (linear, P < 0.01) decreased with increasing P concentrations.
      True ileal P digestibility and true P retention coefficients of corn were
      determined to be 0.676 and 0.632, respectively. The corresponding values for
      canola meal were 0.469 and 0.486, respectively. In both ingredients, the
      determined true ileal digestibility and total tract retention coefficients were
      not different (P > 0.05). Total P, nonphytate P, true digestible P, and true
      retainable P contents of corn were determined to be 2.5, 0.8, 1.7, and 1.6 g/kg
      (as received), respectively. The corresponding values for canola meal were 9.7,
      2.8, 4.6, and 4.7 g/kg (as received), respectively. The present data demonstrated
      that the regression method can be successfully used to measure true P
      digestibility of low and high P feed ingredients and that both true ileal
      digestibility and retention coefficients are suitable to assess P availability in
      broilers.

PMID- 24570461
TI  - Efficacy of in-feed preparations of an anticoccidial, multienzyme, prebiotic,
      probiotic, and herbal essential oil mixture in healthy and Eimeria spp.-infected
      broilers.
AB  - The efficacies of 5 widely used dietary supplements were investigated on
      performance indices, fecal oocyst excretion, lesion score, and intestinal tract
      measurements in healthy and Eimeria spp.-infected birds by using a comparative
      model. This study included 2,400 sexed Ross 308 broiler chicks that were equally
      divided in 2 groups: the infected group, experimentally infected with oocysts of
      mixed Eimeria spp. at 14 d of age, and the healthy controls. The birds in both
      groups were further divided equally into 6 groups, of which one was fed a basal
      diet and served as control without treatment and the other 5 served as
      experimental treatments. These 5 groups were fed 5 diets containing preparations
      of 60 mg/kg of anticoccidial salinomycin (SAL), 1 g/kg of multienzyme (ENZ), 1
      g/kg of probiotic (PRO), 1 g/kg of prebiotic (PRE), and 40 mg/kg of an herbal
      essential oil mixture (EOM). Body weight gain and feed conversion ratio (FCR)
      showed significant improvement in the infected animals, which indicates that
      dietary supplemental regimens with SAL, ENZ, PRO, and PRE initiated in 1-d-old
      chicks reduced adverse effects after challenge with coccidiosis; however, chicks
      that were administered EOM failed to show such improvement. Uninfected chickens
      showed significant improvement in FCR with supplements SAL, PRE, and EOM, which
      signifies significant (P < 0.01) infection by supplement interactions for BW gain
      and FCR. In the infected group, all of the supplements reduced the severity of
      coccidiosis lesions (P < 0.01) induced by mixed Eimeria spp. through the middle
      and lower regions of the small intestines, whereas supplementation with SAL or
      EOM alone was effective (P < 0.01) in reducing oocyst excretion compared with the
      control treatment. The data indicated that use of these subtherapeutically
      efficacious supplements (except EOM) in broiler production can lessen the
      depression in growth due to coccidial challenge. 

PMID- 24570464
TI  - Standardized ileal amino acid digestibility of meat and bone meal and soybean
      meal in laying hens and broilers.
AB  - The objective of this study was to determine the standardized ileal amino acid
      digestibility (SIAAD) of 7 meat and bone meal (MBM) and 3 soybean meal (SBM)
      samples in broilers (Ross 708) and laying hens (Hy-line W36). All 10 feed
      ingredients were evaluated in 21-d-old broiler chickens and 30- or 50-wk-old
      laying hens. Standardization was accomplished by correcting for basal ileal
      endogenous amino acid losses using a nitrogen-free diet. Broilers were reared in
      cages from d 0 to 16 on a standard broiler starter diet adequate in all nutrients
      and energy; thereafter, they were allotted to treatments using a randomized
      complete design with 6 replicate cages of 8 birds each. For the laying hens, 6
      replicate cages of 6 birds each (542 cm(2)/bird) were used. Each treatment diet,
      which was fed for 5 d, was semipurified, with MBM or SBM being the sole source of
      amino acids in each diet. Ileal endogenous amino acid losses were not different
      between broilers and the 2 groups of laying hens. Meat and bone meal from
      different locations varied widely in digestibility. Broilers had higher (P <
      0.05) SIAAD in 4 of the 7 MBM samples. In 2 of the 3 SBM samples, broilers had
      higher (P < 0.05) SIAAD for most of the nonessential amino acids. Generally, hens
      had 6.4 and 7.7% units less Met and Lys digestibility of all MBM samples after
      standardization. Dry matter digestibility values of the SBM samples were higher
      (P < 0.05) in broilers. Likewise, broilers had 4.1 and 1.5% units more Met and
      Lys digestibility of all the SBM samples evaluated compared with those from
      laying hens. The results of these experiments suggest that differences exist in
      the digestive capabilities of laying hens and broilers, which indicates that
      species-specific nutrient digestibility values or adjustments may be needed. 

PMID- 24570465
TI  - The spleen accumulates advanced glycation end products in the chicken: tissue
      comparison made with rat.
AB  - Glycation starts from nonenzymatic amino-carbonyl reaction that binds carbonyl
      group of reducing sugars to the amino group of amino acids. Glycation leads to
      further complex reactions to form advanced glycation end products (AGE). Because
      AGE are implicated in the gradual development of diabetic complications, tissue
      accumulation of AGE has been widely examined in various tissues of rats. Avian
      species are known to have high body temperature and blood glucose concentration
      compared with mammals. Although these characteristics enabled chickens to be used
      as experimental models for diabetes mellitus, the information of AGE accumulation
      in various tissues of chickens has not been limited so far. In the present study,
      therefore, the radioactive AGE prepared by reacting (14)C-glucose and amino acids
      were intravenously administrated, and comparison of tissue accumulation of (14)C
      labeled AGE was made between chickens and rats. At 30 min after administration,
      tissues (18-20) were collected, and the radioactivity incorporated into tissues
      was determined. High levels of radioactivity per gram of tissue in the liver and
      kidney were observed in both rats and chickens. In chickens but not rats, a large
      amount of (14)C-labeled AGE incorporated into 1 g of spleen was observed, and the
      specific accumulation of AGE in the avian spleen might have a particular role in
      immune response in avian species. 

PMID- 24570466
TI  - Yerba mate enhances probiotic bacteria growth in vitro but as a feed additive
      does not reduce Salmonella Enteritidis colonization in vivo.
AB  - Yerba mate (Ilex paraguariensis) is a tea known to have beneficial effects on
      human health and antimicrobial activity against some foodborne pathogens. Thus,
      the application of yerba mate as a feed additive for broiler chickens to reduce
      Salmonella colonization was evaluated. The first in vitro evaluation was
      conducted by suspending Salmonella Enteritidis and lactic acid bacteria (LAB) in
      yerba mate extract. The in vivo evaluations were conducted using preventative and
      horizontal transmission experiments. In all experiments, day-of-hatch chicks were
      treated with one of the following 1) no treatment (control); 2) ground yerba mate
      in feed; 3) probiotic treatment (Lactobacillus acidophilus and Pediococcus; 9:1
      administered once on day of hatch by gavage); or 4) both yerba mate and probiotic
      treatments. At d 3, all chicks were challenged with Salmonella Enteritidis
      (preventative experiment) or 5 of 20 chicks (horizontal transmission experiment).
      At d 10, all birds were euthanized, weighed, and cecal contents enumerated for
      Salmonella. For the in vitro evaluation, antimicrobial activity was observed
      against Salmonella and the same treatment enhanced growth of LAB. For in vivo
      evaluations, none of the yerba mate treatments significantly reduced Salmonella
      Enteritidis colonization, whereas the probiotic treatment significantly reduced
      Salmonella colonization in the horizontal transmission experiment. Yerba mate
      decreased chicken BW and decreased the performance of the probiotic treatment
      when used in combination. In conclusion, yerba mate had antimicrobial activity
      against foodborne pathogens and enhanced the growth of LAB in vitro, but in vivo
      yerba mate did not decrease Salmonella Enteritidis colonization. 

PMID- 24570467
TI  - Survival of Salmonella enterica in poultry feed is strain dependent.
AB  - Feed components have low water activity, making bacterial survival difficult. The
      mechanisms of Salmonella survival in feed and subsequent colonization of poultry
      are unknown. The purpose of this research was to compare the ability of
      Salmonella serovars and strains to survive in broiler feed and to evaluate
      molecular mechanisms associated with survival and colonization by measuring the
      expression of genes associated with colonization (hilA, invA) and survival via
      fatty acid synthesis (cfa, fabA, fabB, fabD). Feed was inoculated with 1 of 15
      strains of Salmonella enterica consisting of 11 serovars (Typhimurium,
      Enteriditis, Kentucky, Seftenburg, Heidelberg, Mbandanka, Newport, Bairely,
      Javiana, Montevideo, and Infantis). To inoculate feed, cultures were suspended in
      PBS and survival was evaluated by plating samples onto XLT4 agar plates at
      specific time points (0 h, 4 h, 8 h, 24 h, 4 d, and 7 d). To evaluate gene
      expression, RNA was extracted from the samples at the specific time points (0, 4,
      8, and 24 h) and gene expression measured with real-time PCR. The largest
      reduction in Salmonella occurred at the first and third sampling time points (4 h
      and 4 d) with the average reductions being 1.9 and 1.6 log cfu per g,
      respectively. For the remaining time points (8 h, 24 h, and 7 d), the average
      reduction was less than 1 log cfu per g (0.6, 0.4, and 0.6, respectively). Most
      strains upregulated cfa (cyclopropane fatty acid synthesis) within 8 h, which
      would modify the fluidity of the cell wall to aid in survival. There was a weak
      negative correlation between survival and virulence gene expression indicating
      downregulation to focus energy on other gene expression efforts such as survival
      related genes. These data indicate the ability of strains to survive over time in
      poultry feed was strain dependent and that upregulation of cyclopropane fatty
      acid synthesis and downregulation of virulence genes were associated with a
      response to desiccation stress. 

PMID- 24570469
TI  - Effect of thyme/cumin essential oils and butylated hydroxyl anisole/butylated
      hydroxyl toluene on physicochemical properties and oxidative/microbial stability
      of chicken patties.
AB  - In this study, effects of thyme/cumin essential oils (EO) and butylated hydroxyl
      anisole (BHA)/butylated hydroxyl toluene (BHT) on physicochemical properties and
      storage stability of chicken patties were compared in different storage periods
      (0, 3, 7, 14, 21, and 28 d). It was found that there were significant (P < 0.05)
      differences between physicochemical properties of patty samples treated with EO
      and the synthetic antioxidants. The EO showed similar performance to those of BHA
      and BHT in limiting TBARS values of chicken patty samples. Similarity in
      performance was also the case for microbial stability (total aerobic mesophilic,
      psychrotrophic, lactic acid, and coliform bacteria as well as molds and yeasts);
      namely, their effects were significant (P < 0.05). Effect of thyme EO was
      significant (P < 0.05) and remarkable, not allowing any coliform bacteria to grow
      in the samples. Given that EO were obtained from natural sources, the data
      suggested that the EO might be more useful than their synthetic counterparts, BHA
      and BHT, as additives for chicken patties to maintain oxidative/microbial
      stability and increase shelf life. 

PMID- 24570470
TI  - The effects of different eggshell temperatures on embryonic development,
      hatchability, chick quality, and first-week broiler performance.
AB  - The aim of the current study was to determine the effects of different eggshell
      temperatures (EST) during 10 to 18 d of incubation on embryonic development,
      hatchability, chick quality, first-week broiler performance. The EST were
      maintained within the temperature ranges of 33.3 to 36.7, 37.8 to 38.2, and 38.9
      to 40.0 degrees C for the low, control, and high EST treatments, respectively.
      From d 15 to 18, embryo weight and relative embryo weight were found to be
      similar in the low and high EST groups. Salable chicks and hatchability of total
      eggs was found to be higher in the control EST group. Between d 10 and 17 of
      incubation, embryonic mortality in low, control, and high EST groups was
      determined to be 1.6, 0.8, and 2.0%, respectively. From d 18 to hatch, embryonic
      mortality and rate of dead and cull chicks were found to be significantly
      different. Hatching in high EST group was completed 26 h early, although hatching
      in low EST group was completed 10 h later than the control EST group. On the of
      hatching day, chick weight and length were found to be 39.5, 41.0, and 42.5 g,
      and 18.5, 21.4, and 19.1 cm in low, control, and high EST groups, respectively.
      The highest residual yolk sac weight and relative residual yolk sac weight were
      observed in high EST group as 7.7 g and 18.7%. Yolk-free chick weight and
      relative yolk-free chick weight were highest in the control EST group. At 1 wk of
      age, the BW in low, control, and high EST groups were determined as 131.1, 140.0,
      and 140.8 g, respectively. No significant difference was found for feed intake
      and feed conversion among treatments for wk 1. The mortality during the first
      week did not differ among groups; however, a higher mortality rate was observed
      numerically in the high EST group. In conclusion, embryo development, incubation
      parameters, chick quality, and the first week performance are affected by small
      changes in the EST.

PMID- 24570468
TI  - Evaluation of a commercially available organic acid product on body weight loss,
      carcass yield, and meat quality during preslaughter feed withdrawal in broiler
      chickens: a poultry welfare and economic perspective.
AB  - The effect of a commercial organic acid (OA) product on BW loss (BWL) during feed
      withdrawal and transportation, carcass yield, and meat quality was evaluated in
      broiler chickens. Two experiments were conducted in Brazil. Commercial houses
      were paired as control groups receiving regular water and treated groups
      receiving OA in the water. Treated birds had a reduction in BWL of 37 g in
      experiment 1 and 32.2 g in experiment 2. In experiment 2, no differences were
      observed in carcass yield between groups. Estimation of the cost benefit
      suggested a 1:16 ratio by using the OA. In experiment 3, conducted in Mexico,
      significant differences on water consumption, BWL, and meat quality
      characteristics were observed in chickens that were treated with the OA (P <
      0.05). These data suggest this OA product may improve animal welfare and economic
      concerns in the poultry industry by reducing BWL and improving meat quality
      attributes. 

PMID- 24570471
TI  - Effects of breeder age on mineral contents and weight of yolk sac, embryo
      development, and hatchability in Pekin ducks.
AB  - The current study was carried out to investigate the effects of breeder age on
      egg composition, changes of embryo, yolk sac, and yolk minerals during incubation
      and hatchability in Pekin ducks. A total of 495 freshly laid eggs were obtained
      from the same flock of Pekin ducks, aged 28, 34, and 40 wk, and were reared in
      accordance with the management guide of the duck breeders (Star 53-Grimaud
      Freres). At each breeder age, egg measurements were made on a random subsample of
      unincubated eggs. Embryo and yolk sac measurements were made on embryonic day (E)
      12, E16, E20, and E25. On d 28 of incubation, the healthy ducklings were removed
      and sex of chicks was determined. All chicks were weighed and hatching results
      were determined. Egg weight and yolk percentages increased; however, albumen
      percentages, shell thickness, and yolk index decreased as the flock aged. Shell
      percentages, shell breaking strength, albumen index, and haugh units were not
      affected by breeder age. Also, breeder age affected the Mg, P, K, Ca, Cu, and Zn
      levels in the yolk, except for Na level on day of setting, and breeder age
      affected the mineral consumed by embryo during incubation. However, on E25, the
      levels of examined minerals, except for P level in the yolk sac, were not
      statistically different in duck breeder age groups. Relative yolk sac and embryo
      weights of eggs obtained from different breeder ages varied from E16 to E25;
      however, embryo length was different in breeder age groups from E12 to E20.
      Hatching weight was affected by breeder age and sex. Hatching results were not
      different among breeder age groups. This study indicates that breeder age is
      important for some egg characteristics, relative yolk sac weight, some contents
      of minerals in the yolk, embryonic growth during incubation, and duckling weight.

PMID- 24570472
TI  - Next-generation sequencing strategies for characterizing the turkey genome.
AB  - The turkey genome sequencing project was initiated in 2008 and has relied
      primarily on next-generation sequencing (NGS) technologies. Our first efforts
      used a synergistic combination of 2 NGS platforms (Roche/454 and Illumina GAII),
      detailed bacterial artificial chromosome (BAC) maps, and unique assembly tools to
      sequence and assemble the genome of the domesticated turkey, Meleagris gallopavo.
      Since the first release in 2010, efforts to improve the genome assembly, gene
      annotation, and genomic analyses continue. The initial assembly build (2.01)
      represented about 89% of the genome sequence with 17X coverage depth (931 Mb).
      Sequence contigs were assigned to 30 of the 40 chromosomes with approximately 10%
      of the assembled sequence corresponding to unassigned chromosomes (ChrUn). The
      sequence has been refined through both genome-wide and area-focused sequencing,
      including shotgun and paired-end sequencing, and targeted sequencing of
      chromosomal regions with low or incomplete coverage. These additional efforts
      have improved the sequence assembly resulting in 2 subsequent genome builds of
      higher genome coverage (25X/Build3.0 and 30X/Build4.0) with a current sequence
      totaling 1,010 Mb. Further, BAC with end sequences assigned to the Z/W and MG18
      (MHC) chromosomes, ChrUn, or not placed in the previous build were isolated,
      deeply sequenced (Hi-Seq), and incorporated into the latest build (5.0). To aid
      in the annotation and to generate a gene expression atlas of major tissues, a
      comprehensive set of RNA samples was collected at various developmental stages of
      female and male turkeys. Transcriptome sequencing data (using Illumina Hi-Seq)
      will provide information to enhance the final assembly and ultimately improve
      sequence annotation. The most current sequence covers more than 95% of the turkey
      genome and should yield a much improved gene level of annotation, making it a
      valuable resource for studying genetic variations underlying economically
      important traits in poultry. 

PMID- 24570473
TI  - RNA-seq analysis revealed novel genes and signaling pathway associated with
      disease resistance to avian influenza virus infection in chickens.
AB  - Avian influenza virus (AIV) is a type A virus of the family Orthomyxoviridae.
      Avian influenza virus infection can cause significant economic losses to the
      poultry industry, and raises a great public health threat due to potential host
      jump from animals to humans. To develop more effective intervention strategies to
      prevent and control AIV infection in poultry, it is essential to elucidate
      molecular mechanisms of host response to AIV infection in chickens. The objective
      of this study was to identify genes and signal pathways associated with
      resistance to AIV infection in 2 genetically distinct highly inbred chicken lines
      (Fayoumi, relatively resistant to AIV infection, and Leghorn, susceptible to AIV
      infection). Three-week-old chickens were inoculated with 10(7) EID50 of low
      pathogenic H5N3 AIV, and lungs and trachea were harvested 4 d postinoculation.
      Four cDNA libraries (1 library each for infected and noninfected Leghorn, and
      infected and noninfected Fayoumi) were prepared from the lung samples and
      sequenced by Illumina Genome Analyzer II, which yielded a total of 116 million,
      75-bp single-end reads. Gene expression levels of all annotated chicken genes
      were analyzed using CLC Genomics Workbench. DESeq was used to identify
      differentially expressed transcripts between infected and noninfected birds and
      between genetic lines (false discovery rate < 0.05 and fold-change > 2). Of the
      expressed transcripts in a total of 17,108 annotated chicken genes in Ensembl
      database, 82.44 and 81.40% were identified in Leghorn and Fayoumi birds,
      respectively. The bioinformatics analysis suggests that the hemoglobin family
      genes, the functional involvements for oxygen transportation and circulation, and
      cell adhesion molecule signaling pathway play significant roles in disease
      resistance to AIV infection in chickens. Further investigation of the roles of
      these candidate genes and signaling pathways in the regulation of host-AIV
      interaction can lead new directions for the development of antiviral drugs or
      vaccines in poultry. 

PMID- 24570474
TI  - The value of resequence data for poultry breeding: a primary layer breeder
      perspective.
AB  - Poultry breeding companies are facing a new paradigm. Since 2004, extensive
      resources have been developed to increase understanding of the fundamental
      biology of the chicken. The chicken genome has been sequenced and revised twice,
      millions of novel DNA variants have been identified, and new tools have been
      created that allow rapid and inexpensive detection of these DNA variations. These
      developments have led to the establishment of molecular-based breeding programs
      within major poultry breeding companies that are revolutionizing the primary
      poultry breeding industries. Costs of sequencing continue to drop and are
      predicted to eventually reach the point where it is feasible to sequence the
      entire genome of elite birds before selection. There are multiple challenges to
      be resolved before this information can be fully incorporated into a breeding
      program. These include handling and analyzing the extremely large data sets
      generated, understanding which genes, variants, or both are relevant for
      commercial production traits, development of new bio-informatic tools, and
      integration of molecular information with traditional breeding programs. The
      novel variation identified within elite commercial lines will lead to
      enhancements in commercial breeding programs. Applications of this information
      include whole genomic selection, parentage identification, trait association
      studies, and quality control. 

PMID- 24570475
TI  - Epley and beyond: an update on treating positional vertigo.
AB  - Benign paroxysmal positional vertigo (BPPV) is the commonest cause of dizziness.
      It is characterised by brief episodes of vertigo and imbalance with nystagmus.
      The direction of nystagmus allows the identification of the culprit semicircular
      canal. As it is readily treatable--and often curable--BPPV should not be missed.
      Although recurrent episodes of vertigo triggered by movement suggest BPPV, the
      diagnosis can only be confirmed with the Dix-Hallpike manoeuvre. Here we review
      the diagnostic manoeuvres required to diagnose BPPV, and the various
      repositioning manoeuvres for treating different types of BPPV.

PMID- 24570476
TI  - Clinical assessment of the sensory ataxias; diagnostic algorithm with
      illustrative cases.
AB  - Ataxia is a common neurological syndrome resulting from cerebellar, vestibular or
      sensory disorders. The recognition and characterisation of sensory ataxia remains
      a challenge. Cerebellar ataxia is the more common and easier to identify; sensory
      ataxia is often mistaken for cerebellar ataxia, leading to diagnostic errors and
      delays. A coherent aetiological work-up is only possible if clinicians initially
      recognise sensory ataxia. We discuss ways to separate sensory from cerebellar
      ataxia, the causes of sensory ataxia and the clinico-neurophysiological syndromes
      causing the sensory ataxia syndromes. We summarise a logical tiered approach as a
      diagnostic algorithm. 

PMID- 24570477
TI  - Airway stem cells and lung cancer.
AB  - Lung cancer is the biggest cancer killer in the UK and despite recent therapeutic
      advances there is a desperate need for new therapies to improve outcomes from
      this devastating disease. Through defining the spatial location of the airway
      epithelial stem or progenitor cell populations and their mechanisms of
      maintenance and repair of the epithelium it is becoming clear that these
      populations are situated at areas corresponding to those involved in lung cancer
      initiation. We explore the evidence for stem cells being the cancer initiator
      cell and for a 'lung cancer stem cell' within tumours that may be the cause of
      resistance to current therapies.

PMID- 24570478
TI  - Survival of patients with ANCA-associated vasculitis on chronic dialysis: data
      from the French REIN registry from 2002 to 2011.
AB  - BACKGROUND: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides
      (AAV) can lead to end-stage renal disease in patients with renal involvement.
      OBJECTIVE: This study evaluated the survival of AAV patients on chronic dialysis
      in France. METHODS: Between 2002 and 2011, a total of 425 AAV patients started
      chronic dialysis and were registered in the Renal Epidemiology and Information
      Network. We analysed survival censored for renal transplantation, recovery of
      renal function and loss to follow-up. AAV patients were compared with 794 matched
      non-AAV patients on chronic dialysis. RESULTS: A total of 166 (39%) patients with
      microscopic polyangiitis and 259 (61%) patients with granulomatosis with
      polyangiitis were registered. Within a median follow-up of 23 months, 58 (14%)
      patients received a renal allograft and 19 (4%) recovered renal function. Median
      survival on dialysis was 5.35 years (95% CI, 4.4-6.3) and survival rates at 3
      months, 1, 3 and 5 years were 96%, 85%, 68% and 53%, respectively. A total of 143
      (41%) patients died after a median of 16 months. Causes of death were
      cardiovascular (29%), infections (20%), malnutrition (13%), malignancies (4%),
      AAV relapse (2%), miscellaneous (14%) and unknown (18%). Multivariate logistic
      regression identified three independent risk factors associated with AAV
      patients' mortality: age (HR = 1.05/year, P < 0.001), peripheral artery disease
      (HR = 2.62, P = 0.003) and frailty (HR = 2.43, P < 0.001). Survival of AAV
      patients did not differ from non-AAV controls, but infectious mortality was
      higher in AAV patients (20% vs. 8%, P < 0.001). CONCLUSION: Survival of AAV
      patients in chronic dialysis, although poor, was comparable to survival of non
      AAV controls on dialysis. There was a similar burden of cardiovascular mortality,
      but higher infectious mortality.

PMID- 24570479
TI  - Cardiologist service volume, percutaneous coronary intervention and hospital
      level in relation to medical costs and mortality in patients with acute
      myocardial infarction: a nationwide study.
AB  - BACKGROUND: We explore whether cardiologist service volume, hospital level and
      percutaneous coronary intervention (PCI) are associated with medical costs and
      acute myocardial infarction (AMI) mortality. METHODS: From the 1997-2010 Taiwan
      National Health Insurance Research Database of the National Health Research
      Institute, we identified AMI patients and performed multiple regression analyses
      to explore the relationships among the different hospital levels and treatment
      factors. RESULTS: We identified 2942 patients with AMI in medical centers and
      4325 patients with AMI in regional hospitals. Cardiologist service volume,
      performing PCI and medical costs per patient were higher in medical centers than
      in regional hospitals (P < 0.0001). However, the two hospital levels did not
      differ significantly in in-hospital mortality (P = 0.1557). Post hoc analysis
      showed significant differences in in-hospital mortality rate and in medical costs
      among the eight groups subdivided on the basis of hospital level, cardiologist
      service volume, and whether PCI was performed (P < 0.001 and P = 0.001,
      respectively). CONCLUSIONS: These results highlight the importance of encouraging
      hospitals to develop PCI capability and increase their cardiologist service
      volume after taking medical costs into account. Transferring AMI patients to
      hospitals with higher cardiologist service volume and PCI performed can also be
      very important.

PMID- 24570480
TI  - Melatonin deprival modifies follicular and corpus luteal growth dynamics in a
      sheep model.
AB  - This study assessed the effect of melatonin deprival on ovarian status and
      function in sheep. Experimental procedures were carried out within two
      consecutive breeding seasons. Animals were divided into two groups:
      pinealectomised (n=6) and sham-operated (n=6). The completeness of the pineal
      gland removal was confirmed by the plasma concentration of melatonin. Ovarian
      status was monitored by ovarian ultrasonography for 1 year to study reproductive
      seasonality. Follicular and corpus luteal growth dynamics were assessed during an
      induced oestrous cycle. As the effects of melatonin on the ovary may also be
      mediated by its antioxidant properties, plasma Trolox equivalent antioxidant
      capacity (TEAC) was determined monthly for 1 year. Pinealectomy significantly
      extended the breeding season (310+/-24.7 vs 217.5+/-24.7 days in controls;
      P<0.05). Both pinealectomised and sham-operated ewes showed a well-defined wave
      like pattern of follicle dynamics; however, melatonin deficiency caused fewer
      waves during the oestrous cycle (4.3+/-0.2 vs 5.2+/-0.2; P<0.05), because waves
      were 1 day longer when compared with the controls (7.2+/-0.3 vs 6.1+/-0.3;
      P<0.05). The mean area of the corpora lutea (105.4+/-5.9 vs 65.4+/-5.9 mm(2);
      P<0.05) and plasma progesterone levels (7.1+/-0.7 vs 4.9+/-0.6 ng/ml; P<0.05)
      were significantly higher in sham-operated ewes compared with pinealectomised
      ewes. In addition, TEAC values were significantly lower in pinealectomised ewes
      compared with control ones. These data suggest that melatonin, besides exerting
      its well-known role in the synchronisation of seasonal reproductive fluctuations,
      influences the growth pattern of the follicles and the steroidogenic capacity of
      the corpus luteum.

PMID- 24570481
TI  - A single inhibitory upstream open reading frame (uORF) is sufficient to regulate
      Candida albicans GCN4 translation in response to amino acid starvation
      conditions.
AB  - Candida albicans is a major fungal pathogen that responds to various
      environmental cues as part of its infection mechanism. We show here that the
      expression of C. albicans GCN4, which encodes a transcription factor that
      regulates morphogenetic and metabolic responses, is translationally regulated in
      response to amino acid starvation induced by exposure to the histidine analog 3
      aminotriazole (3AT). However, in contrast to the well-known translational control
      mechanisms that regulate yeast GCN4 and mammalian ATF4 expression via multiple
      upstream open reading frames (uORFs) in their 5'-leader sequences, a single
      inhibitory uORF is necessary and sufficient for C. albicans GCN4 translational
      control. The 5'-leader sequence of GCN4 contains three uORFs, but uORF3 alone is
      sufficient for translational regulation. Under nonstress conditions, uORF3
      inhibits GCN4 translation. Amino acid starvation conditions promote Gcn2-mediated
      phosphorylation of eIF2alpha and leaky ribosomal scanning to bypass uORF3,
      inducing GCN4 translation. GCN4 expression is also transcriptionally regulated,
      although maximal induction is observed at higher concentrations of 3AT compared
      with translational regulation. C. albicans GCN4 expression is therefore highly
      regulated by both transcriptional and translational control mechanisms. We
      suggest that it is particularly important that Gcn4 levels are tightly controlled
      since Gcn4 regulates morphogenetic changes during amino acid starvation
      conditions, which are important determinants of virulence in this fungus. 

PMID- 24570484
TI  - Thailand radiation monitoring program: a preliminary result analysis of the
      country's background radiation.
AB  - Environmental monitoring in the context of nuclear-related activities refers to
      the measurements of ambient gamma dose rates in the environment and radioactivity
      in air, water, soil etc. Since nuclear power programme in Thailand has not yet
      been in place, the environment surveillance programme in Thailand currently
      focuses on establishing 'baseline' environmental radiation levels and
      radioactivity for the purpose of establishing impacts of future possible sources
      such as nuclear accidents. The objective is to assure assessments concerning
      radiation safety for the environment and public. At present, Thailand's
      monitoring programme operates eight fixed monitoring stations installed in
      various regions of Thailand; four of which have been in operation since late
      2010. The ambient gamma dose rate data are routinely collected from those four
      real-time monitoring stations starting from October 2010 to September 2011 as
      described in this study. Also, the radiation data from each station are
      statically analysed. This study found that the dose rate from the stations
      located in north and north-east of Thailand showed an apparent tendency towards a
      diurnal pattern. With these routine data, the average exposure dose rate was
      possible to estimate in Thailand. Additionally, the assessment of the equivalent
      dose from natural background radiation was estimated. 

PMID- 24570482
TI  - An RNA aptamer possessing a novel monovalent cation-mediated fold inhibits
      lysozyme catalysis by inhibiting the binding of long natural substrates.
AB  - RNA aptamers are being developed as inhibitors of macromolecular and cellular
      function, diagnostic tools, and potential therapeutics. Our understanding of the
      physical nature of this emerging class of nucleic acid-protein complexes is
      limited; few atomic resolution structures have been reported for aptamers bound
      to their protein target. Guided by chemical mapping, we systematically minimized
      an RNA aptamer (Lys1) selected against hen egg white lysozyme. The resultant 59
      nucleotide compact aptamer (Lys1.2minE) retains nanomolar binding affinity and
      the ability to inhibit lysozyme's catalytic activity. Our 2.0-A crystal structure
      of the aptamer-protein complex reveals a helical stem stabilizing two loops to
      form a protein binding platform that binds lysozyme distal to the catalytic
      cleft. This structure along with complementary solution analyses illuminate a
      novel protein-nucleic acid interface; (1) only 410 A(2) of solvent accessible
      surface are buried by aptamer binding; (2) an unusually small fraction (~18%) of
      the RNA-protein interaction is electrostatic, consistent with the limited protein
      phosphate backbone contacts observed in the structure; (3) a single Na(+)
      stabilizes the loops that constitute the protein-binding platform, and consistent
      with this observation, Lys1.2minE-lysozyme complex formation takes up rather than
      displaces cations at low ionic strength; (4) Lys1.2minE inhibits catalysis of
      large cell wall substrates but not catalysis of small model substrates; and (5)
      the helical stem of Lys1.2minE can be shortened to four base pairs (Lys1.2minF)
      without compromising binding affinity, yielding a 45-nucleotide aptamer whose
      structure may be an adaptable protein binding platform. 

PMID- 24570485
TI  - Genital warts and chlamydia in Australian women: comparison of national
      population-based surveys in 2001 and 2011.
AB  - OBJECTIVES: Australia introduced a nationwide human papillomavirus (HPV)
      vaccination programme for women aged 12-26 years in 2007 and has implemented
      various chlamydia control strategies over the last 10 years. We compared reported
      diagnoses of warts and chlamydia in two national population-based samples
      surveyed 10 years apart. METHODS: An Australia-wide survey of women aged 18-39
      years was conducted by random-digit dialling mobile phone numbers in 2011. The
      proportion of women self-reporting genital warts and chlamydia was compared with
      that in equivalent-aged women interviewed in another national telephone survey
      conducted 10 years earlier using logistic regression adjusting for age, and other
      factors. RESULTS: 2394 women were included in the 2011 survey. 88 (3.7%) reported
      a genital warts diagnosis, and 127 (5.3%) had at least one chlamydia diagnosis.
      For women with warts and chlamydia, the majority were seen in general practice
      (63.3% and 70.0%, respectively). Comparing women surveyed in 2011 to 4874 women
      surveyed in 2001, among women eligible for free HPV vaccine through the national
      programme (women aged 18-30 years), there was a 41% decrease in warts (adjusted
      OR 0.59, 95% CI 0.39 to 0.89) but among ineligible women (31-39 years) there was
      a 64% increase (aOR 1.64, 95% CI 1.05 to 2.54). Over the same period chlamydia
      diagnoses increased by 97% (aOR 1.97, 95% CI 1.15 to 3.37) in women aged 18-24
      years. CONCLUSIONS: Our results add to evidence from clinic-based studies showing
      a significant reduction in genital warts among HPV vaccine-eligible women in the
      general community and increases in the proportion of Australian women diagnosed
      with chlamydia.

PMID- 24570483
TI  - Principles of ion recognition in RNA: insights from the group II intron
      structures.
AB  - Metal ions promote both RNA folding and catalysis, thus being essential in
      stabilizing the structure and determining the function of large RNA molecules,
      including group II introns. The latter are self-splicing metalloribozymes,
      containing a heteronuclear four-metal-ion center within the active site. In
      addition to these catalytic ions, group II introns bind many other structural
      ions, including delocalized ions that bind the RNA diffusively and well-ordered
      ions that bind the RNA tightly with high occupancy. The latter ions, which can be
      studied by biophysical methods, have not yet been analyzed systematically. Here,
      we compare crystal structures of the group IIC intron from Oceanobacillus
      iheyensis and classify numerous site-bound ions, which are primarily localized in
      the intron core and near long-range tertiary contacts. Certain ion-binding sites
      resemble motifs observed in known RNA structures, while others are idiosyncratic
      to the group II intron. Particularly interesting are (1) ions proximal to the
      active site, which may participate in splicing together with the catalytic four
      metal-ion center, (2) organic ions that bind regions predicted to interact with
      intron-encoded proteins, and (3) unusual monovalent ions bound to GU wobble
      pairs, GA mismatches, the S-turn, the tetraloop-receptor, and the T-loop. Our
      analysis extends the general principles by which ions participate in RNA
      structural organization and it will aid in the determination and interpretation
      of future RNA structures. 

PMID- 24570486
TI  - mTORC1 promotes denervation-induced muscle atrophy through a mechanism involving
      the activation of FoxO and E3 ubiquitin ligases.
AB  - Skeletal muscle mass and function are regulated by motor innervation, and
      denervation results in muscle atrophy. The activity of mammalian target of
      rapamycin complex 1 (mTORC1) is substantially increased in denervated muscle, but
      its regulatory role in denervation-induced atrophy remains unclear. At early
      stages after denervation of skeletal muscle, a pathway involving class II histone
      deacetylases and the transcription factor myogenin mediates denervation-induced
      muscle atrophy. We found that at later stages after denervation of fast-twitch
      muscle, activation of mTORC1 contributed to atrophy and that denervation-induced
      atrophy was mitigated by inhibition of mTORC1 with rapamycin. Activation of
      mTORC1 through genetic deletion of its inhibitor TSC1 (tuberous sclerosis complex
      1) sensitized mice to denervation-induced muscle atrophy and suppressed the
      kinase activity of Akt, leading to activation of FoxO transcription factors and
      increasing the expression of genes encoding E3 ubiquitin ligases atrogin [also
      known as MAFbx (muscle atrophy F-box protein)] and MuRF1 (muscle-specific ring
      finger 1). Rapamycin treatment of mice restored Akt activity, suggesting that the
      denervation-induced increase in mTORC1 activity was producing feedback inhibition
      of Akt. Genetic deletion of the three FoxO isoforms in skeletal muscle induced
      muscle hypertrophy and abolished the late-stage induction of E3 ubiquitin ligases
      after denervation, thereby preventing denervation-induced atrophy. These data
      revealed that mTORC1, which is generally considered to be an important component
      of anabolism, is central to muscle catabolism and atrophy after denervation. This
      mTORC1-FoxO axis represents a potential therapeutic target in neurogenic muscle
      atrophy. 

PMID- 24570487
TI  - Arginine methylation of CRTC2 is critical in the transcriptional control of
      hepatic glucose metabolism.
AB  - Fasting glucose homeostasis is maintained in part through cAMP (adenosine 3',5'
      monophosphate)-dependent transcriptional control of hepatic gluconeogenesis by
      the transcription factor CREB (cAMP response element-binding protein) and its
      coactivator CRTC2 (CREB-regulated transcriptional coactivator 2). We showed that
      PRMT6 (protein arginine methyltransferase 6) promotes fasting-induced
      transcriptional activation of the gluconeogenic program involving CRTC2. Mass
      spectrometric analysis indicated that PRMT6 associated with CRTC2. In cells,
      PRMT6 mediated asymmetric dimethylation of multiple arginine residues of CRTC2,
      which enhanced the association of CRTC2 with CREB on the promoters of
      gluconeogenic enzyme-encoding genes. In mice, ectopic expression of PRMT6
      promoted higher blood glucose concentrations, which were associated with
      increased expression of genes encoding gluconeogenic factors, whereas knockdown
      of hepatic PRMT6 decreased fasting glycemia and improved pyruvate tolerance. The
      abundance of hepatic PRMT6 was increased in mouse models of obesity and insulin
      resistance, and adenovirus-mediated depletion of PRMT6 restored euglycemia in
      these mice. We propose that PRMT6 is involved in the regulation of hepatic
      glucose metabolism in a CRTC2-dependent manner. 

PMID- 24570488
TI  - Tumor necrosis factor suppresses NR5A2 activity and intestinal glucocorticoid
      synthesis to sustain chronic colitis.
AB  - Intestinal crypt epithelial cells synthesize glucocorticoids, steroid hormones
      that protect against inflammatory bowel disease. To investigate how intestinal
      glucocorticoids are regulated during chronic inflammation, we induced chronic
      colitis in mice by exposing them to the chemical dextran sulfate sodium (DSS). We
      found that intestinal glucocorticoid secretion and expression of the genes
      Cyp11a1 and Cyp11b1 (which encode enzymes that synthesize glucocorticoids) were
      initially stimulated, but declined during the chronic phase, whereas tumor
      necrosis factor (TNF) and inflammatory cytokines secreted by T helper type 1
      (TH1) and TH17 cells continuously increased in abundance in the inflamed colon.
      This suggested that inadequate intestinal glucocorticoid synthesis is a feature
      of chronic intestinal inflammation. We screened for cytokines that regulated
      intestinal glucocorticoid synthesis and found that TNF suppressed corticosterone
      secretion and Cyp11a1 and Cyp11b1 expression in an intestinal crypt epithelial
      cell line. TNF suppressed steroidogenesis by activating the transcription factors
      c-Jun and nuclear factor kappaB (NF-kappaB), which both interacted with the
      transcription factor NR5A2 and repressed Cyp11a1 reporter activity. This
      repression was relieved by expression of a dominant-negative form of c-Jun amino
      terminal kinase 1 (JNK1), inhibitor of NF-kappaB, or by a JNK inhibitor.
      Furthermore, the dominant-negative TNF inhibitor XPro1595 inhibited c-Jun and NF
      kappaB activation in mice, restored intestinal Cyp11a1 and Cyp11b1 expression,
      reduced colonic cell death, and rescued chronic colitis caused by DSS. Thus,
      during chronic colitis, TNF suppresses intestinal steroidogenic gene expression
      by inhibiting the activity of NR5A2, thus decreasing glucocorticoid synthesis and
      sustaining chronic inflammation. 

PMID- 24570489
TI  - Yeast osmosensors Hkr1 and Msb2 activate the Hog1 MAPK cascade by different
      mechanisms.
AB  - To cope with environmental high osmolarity, the budding yeast Saccharomyces
      cerevisiae activates the mitogen-activated protein kinase (MAPK) Hog1, which
      controls an array of osmoadaptive responses. Two independent, but functionally
      redundant, osmosensing systems involving the transmembrane sensor histidine
      kinase Sln1 or the tetraspanning membrane protein Sho1 stimulate the Hog1 MAPK
      cascade. Furthermore, the Sho1 signaling branch itself also involves the two
      functionally redundant osmosensors Hkr1 and Msb2. However, any single osmosensor
      (Sln1, Hkr1, or Msb2) is sufficient for osmoadaptation. We found that the
      signaling mechanism by which Hkr1 or Msb2 stimulated the Hog1 cascade was
      specific to each osmosensor. Specifically, activation of Hog1 by Msb2 required
      the scaffold protein Bem1 and the actin cytoskeleton. Bem1 bound to the
      cytoplasmic domain of Msb2 and thus recruited the kinases Ste20 and Cla4 to the
      membrane, where either of them can activate the kinase Ste11. The cytoplasmic
      domain of Hkr1 also contributed to the activation of Ste11 by Ste20, but through
      a mechanism that involved neither Bem1 nor the actin cytoskeleton. Furthermore,
      we found a PXXP motif in Ste20 that specifically bound to the Sho1 SH3 (Src
      homology 3) domain. This interaction between Ste20 and Sho1 contributed to the
      activation of Hog1 by Hkr1, but not by Msb2. These differences between Hkr1 and
      Msb2 may enable differential regulation of these two proteins and provide a
      mechanism through Msb2 to connect regulation of the cytoskeleton with the
      response to osmotic stress. 

PMID- 24570491
TI  - Does early tetralogy of Fallot total correction give better final lung volumes?
AB  - BACKGROUND: Pulmonary blood flow may affect lung development in adulthood. Early
      total correction of tetralogy of Fallot may affect development of final lung
      volumes. We evaluated the effect of age at total correction on lung volumes years
      after the operation. METHODS: In a retrospective cohort study on patients with
      totally corrected tetralogy of Fallot (mean age, 13.40 years at the time of
      follow-up), forced vital capacity, slow vital capacity, forced expiratory volume
      in 1 s, and other parameters were measured 154.8 +/- 46.25 months after the
      operation. Comparison were made of 3 groups: <=2-, 2-8-, and >8-years old at the
      time of total correction surgery. RESULTS: Among 322 enrolled patients, the mean
      values of the follow-up spirometry results in <=2-, 2-8-, >8-year-olds and the
      percentage of predicted values were respectively: vital capacity: 4.46 +/- 0.57 L
      (107% +/- 10.96%), 3.89 +/- 0.58 L (91.10% +/- 12.25%), 3.25 +/- 0.48 L (82.35%
      +/- 10.62%), p < 0.001; forced vital capacity: 4.28 +/- 0.63 L (95.90% +/-
      18.77%), 3.76 +/- 0.58 L (90.83% +/- 12.52%), 3.14 +/- 0.49 L (83.26% +/-
      11.71%), p < 0.001; forced expiratory volume in 1 s: 4.22 +/- 0.63 L (104.84% +/-
      13.64%), 3.66 +/- 0.58 L (90.61% +/- 12.59%), 3.02 +/- 0.48 L (84.31% +/- 12%), p
      < 0.001. CONCLUSION: Early correction of defects or reestablishments of perfusion
      of tetralogy of Fallot before completion of lung development might improve final
      adulthood lung volumes and capacities. It is better to consider total correction
      for all tetralogy of Fallot patients below 2-years old, or at least below 8-years
      old, if it is technically possible.

PMID- 24570490
TI  - Perioperative use of a beta blocker in coronary artery bypass grafting.
AB  - OBJECTIVES: Atrial fibrillation after cardiac surgery is associated with
      increases in the risk of complications, length of intensive care unit stay, and
      cost of care. Beta blockers are effective for controlling myocardial ischemia and
      arrhythmia and suppressing inflammatory cytokines. The purpose of this study was
      to examine the effect of administrating a short-acting beta-adrenoceptor
      antagonist, landiolol, on postoperative atrial fibrillation. METHODS: 136
      patients undergoing off-pump coronary artery bypass grafting were single-blindly
      assigned randomly to landiolol (n = 68) and non-landiolol (control, n = 68)
      groups. In the landiolol group, the beta blocker was administered from the
      beginning of the operation until postoperative day 2. The primary endpoint was
      the incidence of atrial fibrillation until postoperative day 7, and the secondary
      endpoints were the postoperative levels of troponin I, creatine kinase MB
      isoenzyme, and C-reactive protein. RESULTS: The incidence of atrial fibrillation
      was significantly lower in the landiolol group compared to the control group
      (13/68, 19% vs. 25/68, 37%, p = 0.02, logrank test). Landiolol also significantly
      reduced the postoperative peak C-reactive protein level compared to the control
      group (132 +/- 55.4 vs. 161 +/- 50.9 mgcL(-1), p = 0.004). CONCLUSION: Low-dose
      continuous infusion of landiolol reduced the incidence of postoperative atrial
      fibrillation, and significantly suppressed inflammation.

PMID- 24570492
TI  - Normal aortic valves stay open much longer in systole than porcine substitutes.
AB  - OBJECTIVE: To compare the opening mechanics of porcine valve substitutes with
      those of a normal human aortic valve. BACKGROUND: All commercially available
      porcine valves are pretreated with glutaraldehyde. This study was undertaken to
      evaluate the consequences of such treatment on valve mechanics. METHODS: The
      opening mechanics of the aortic valve, especially the time taken to open fully
      from a closed position, and the duration for which the valve is maximally open,
      were compared in a normal aortic valve, a stent-mounted porcine valve, and a
      stentless porcine valve, using a finite element model. RESULTS: Despite a 4-fold
      higher gradient, stent-mounted porcine valves were slower in attaining the fully
      open position, and the time for which the valve was fully open was almost 25%
      less than a normal valve. In stentless valves, the compliant root made the
      initial opening mechanics similar to those of a normal valve. Once this effect
      was over, the effect of porcine leaflet properties took over, and there was a
      corresponding delay in the valve opening. CONCLUSIONS: Fixing the root with a
      stent and stiffening the leaflets with glutaraldehyde result in delayed valve
      opening and decrease the duration for which the valve is fully open, thus
      contributing to inferior hemodynamics.

PMID- 24570493
TI  - Diabetic control and coronary artery bypass: effect on short-term outcomes.
AB  - AIM: To evaluate the effect of preoperative glycemic control on hospital
      morbidity and mortality in diabetic patients undergoing primary coronary artery
      bypass grafting. METHODS: Data of 3857 patients undergoing primary coronary
      artery bypass grafting was prospectively collected and retrospectively analyzed.
      There were 1109 (29%) diabetic patients, of whom 712 (64%) had hemoglobin A1c
      levels recorded. They were categorized by diabetic treatment: diet (179), oral
      hypoglycemic agent, (718) or insulin (212); and by diabetic control: hemoglobin
      A1c < 7 (265) or >=7 (447). Nondiabetic patients (2,748) were used as controls.
      RESULTS: The preoperative risk factors of hypertension (p < 0.001),
      hyperlipidemia (p < 0.001), renal failure (p < 0.04), peripheral vascular disease
      (p < 0.001), and chronic obstructive pulmonary disease (p < 0.04) were
      significantly more prevalent in diabetic patients. Major complications were not
      significantly different between the diabetic and control groups (p = 0.33), but
      minor complications were less frequent in diabetic patients (p = 0.03). Major and
      minor complications were not significantly different among the treatment
      subgroups of diabetic patients (p = 0.74 and p = 0.48) or in those with
      hemoglobin A1c < 7 and >=7 (p = 0.23, p = 0.41). CONCLUSIONS: Short-term outcomes
      were not affected by the degree of preoperative glycemic control or type of
      treatment used in diabetic patients undergoing primary coronary artery bypass
      grafting. A plausible explanation is strict protocol-driven glycemic control in
      the perioperative period.

PMID- 24570494
TI  - Effect of mitral valve replacement on reduction of left atrial size.
AB  - INTRODUCTION: asymptomatic left atrial enlargement is not uncommon in rheumatic
      mitral valve disease. We studied the change in size of the left atrium after
      mitral valve replacement. PATIENTS AND METHODS: between January and December
      2005, 116 patients underwent isolated mitral valve replacement. Two groups were
      identified based on left atrial size: group 1 < 60 mm (n = 79) and group 2 > 60
      mm (n = 37). The patients were followed up for 40.4 +/- 19.3 months Clinical
      assessment, preoperative and last postoperative echocardiograms were considered
      for analysis. RESULTS: the left atrium decreased by 5.84 mm +/- 10.5 in group 1
      compared to 20.9 mm +/- 10.64 in group 2 (p = 0.0001). This correlated with
      preoperative mitral valve area (p = 0.009), preoperative mitral regurgitation (p
      = 0.000), and preoperative atrial fibrillation (p = 0.022). Linear regression
      analysis revealed atrial fibrillation (p = 0.001, b1 = 6.006), a high grade of
      mitral regurgitation (p = 0.001, b1 = -3.812), and larger size of the left atrium
      (p = 0.000, b1 = -0.701) predicted a greater reduction of left atrial size during
      follow-up. Left atrial size decreased by 28 mm in patients with a preoperative
      left atrium >60 mm (75% sensitivity and 100% specificity). CONCLUSION: the
      asymptomatic left atrium reduces in size considerably after mitral valve
      replacement, and the decrease is greater in patients with a left atrium >60 mm in
      size.

PMID- 24570496
TI  - Monitoring pulmonary artery pressure in children undergoing the Fontan procedure.
AB  - OBJECTIVE: To compare external and internal jugular venous pressures to monitor
      pulmonary artery pressure during the Fontan procedure. BACKGROUND: During the
      Fontan procedure, the internal jugular vein is used to assess pulmonary artery
      pressure. The risk of venous thrombosis in the low-pressure Fontan circuit may
      compromise the long-term success of cavopulmonary anastomosis. This study
      compared external and internal jugular venous pressures, femoral venous pressure,
      and actual pulmonary artery pressure during the Fontan procedure. METHOD: 32
      children undergoing a single-stage Fontan on cardiopulmonary bypass were
      monitored for mean external and internal jugular venous pressures and femoral
      venous pressure pre- and post-cardiopulmonary bypass. Pulmonary artery pressure
      was also recorded directly after cardiopulmonary bypass. The pressure data were
      analyzed using analysis of variance, and the coefficient of correlation was
      found. RESULTS: The differences between external jugular, internal jugular, and
      femoral venous pressure pre-cardiopulmonary bypass, and between the 3 venous
      pressures and the pulmonary artery pressure after cardiopulmonary bypass were
      found to be non-significant. The coefficient of correlation of external jugular
      venous pressure and internal jugular venous pressure was 0.8163 (p < 0.0001) pre
      cardiopulmonary bypass, and 0.6465 (p = 0.0001) post-cardiopulmonary bypass.
      CONCLUSION: The external jugular venous pressure correlates well with both
      internal jugular venous pressure and femoral venous pressure as a marker of
      pulmonary artery pressure in children undergoing the Fontan procedure. The use of
      external jugular venous pressure may also preclude the risk of thrombosis.

PMID- 24570495
TI  - Crosslinked acellular saphenous vein for small-diameter vascular graft.
AB  - OBJECTIVE: Patients with congenital and acquired heart diseases or arteriopathy
      require small-diameter vascular grafts for arterial reconstruction. Autologous
      veins are the most suitable graft, but when absent, an alternative is necessary.
      This work addresses the issue. BACKGROUND: Tissue-engineering efforts to create
      such grafts by modifications of acellular natural scaffolds are considered a
      promising area. METHODS: Homologous saphenous veins harvested from cadavers and
      organ donors were processed by decellularization with detergent and enzymatic
      digestion, followed by crosslinking by dye-mediated photooxidation. They were
      validated for acellularity, mechanical strength, and crosslink stability. In
      vitro and in-vivo cytotoxicity and hemocompatibility studies were conducted.
      Collagen conformity was studied by Fourier transform infrared spectroscopy, and
      heat stability by differential scanning calorimetry. A limited large animal study
      was performed. RESULTS: The processing method delivered biocompatible,
      hemocompatible, effectively crosslinked grafts, with high heat stability of 126 ,
      an enthalpy value of 183.5 J.g(-1), and collagen conformity close to that of the
      native vein. The mechanical strength was 250% better than the native vein. The
      presence of extracellular matrix proteins allowed the acellular vein to become a
      triple-layered vascular structure in the sheep venous system. CONCLUSION:
      Crosslinking after decellularization by the dye-mediated photooxidation method
      could be reproduced in any human vein to obtain a small-diameter vascular grafts.

PMID- 24570497
TI  - Mini-invasive diagnosis and synchronous treatment of solitary pulmonary nodule.
AB  - AIM: to develop a simplified method to make a rapid, cost-effective, and precise
      diagnosis of solitary pulmonary nodules, and to perform synchronous treatment of
      solitary pulmonary nodules. METHODS: the solitary pulmonary nodule was located by
      digital palpation, and tissue was acquired with a core biopsy gun. In the
      presence of primary lung cancer, the intervention proceeded to lobectomy. In the
      case of a benign assessment, the whole nodule was wedged out and sent for a
      frozen-section double check: if the benign assessment was confirmed, the patient
      was excluded from further surgery; if the assessment was revised to malignant,
      the intervention proceeded to lobectomy as well as lymphadenectomy. RESULTS: 76
      patients were enrolled. The mean nodule diameter was 1.8 +/- 0.6 cm, the mean
      distance between the visceral pleural and the nodule was 2.4 +/- 1.4 cm, and the
      mean number of punctures was 2.5. The mean time for the phase of intraoperative
      core biopsy was 10 +/- 2 min, and the related blood loss was approximately 5 mL.
      Fifty-six malignant nodules and 20 benign nodules were confirmed. Both the
      sensitivity and accuracy were 100%. CONCLUSION: our results indicate that the
      simplified mini-invasive diagnosis and treatment is an accurate, safe, rapid, and
      cost-saving method, which may translate into fundamentally reducing the medical
      cost and time for lung cancer patients.

PMID- 24570498
TI  - Risk factors for postoperative complications in the elderly with lung cancer.
AB  - BACKGROUND: While surgery for elderly patients has become more common with the
      aging of populations, the relatively high frequency of postoperative
      complications prevents broad application. We retrospectively evaluated prognoses
      after surgery for non-small-cell lung cancer in patients older and younger than
      75 years, to investigate whether age contributes to the risk of a poor outcome.
      PATIENTS AND METHODS: From January 1998 to September 2009, 727 patients underwent
      curative resection for non-small-cell lung cancer in our department; 119 were
      over 75-years old (group 1) and 608 (group 2) were aged less than 75 years.
      RESULTS: The rates of postoperative complications (49% in group 1 and 40% in
      group 2) were not significantly different. Age conferred no significant risk,
      with an odds ratio of 1.129, whereas smoking, blood loss during surgery, and
      lymph node dissection exhibited significant associations. Those aged over 75
      years had a 1.9-fold higher risk of mortality (p < 0.01), but significance did
      not extend to disease-specific survival (p = 0.117). CONCLUSIONS: Postoperative
      complications in elderly non-small-cell lung cancer patients are dependent on
      factors such as smoking, blood loss during surgery, and lymph node dissection,
      but not age. Elderly patients should not be considered ineligible for surgical
      treatment due to their age alone.

PMID- 24570499
TI  - Sternal wrapping: developments and results.
AB  - BACKGROUND: Postoperative sternal wound complications are infrequent events that
      negatively affect recovery and may have serious consequences. Sternal wrapping, a
      technique of sternal care, has hemostatic properties without bone wax, and offers
      mechanical and microbiologic protection. METHODS: From February 1998 to December
      2011, 258 patients in 2 Italian institutions underwent various cardiac surgery
      procedures with sternal wrapping in place, and were followed up for no less then
      6 months. RESULTS: Two (0.8%) extremely compromised patients with ischemic
      sternal osteonecrosis and deep sternal wound infection required a sternal
      stabilizing procedure. Four (2%) other patients developed sternal wound
      complications that were treated entirely medically; 3 of them were very trivial,
      and 1 was an atypical mediastinitis without sternal involvement. Overall, 46.1%
      of patients (45.3% of isolated coronary artery bypass, 49.3% of isolated on-pump
      coronary artery bypass, and 18.2% of off-pump coronary artery bypass patients)
      were transfused. None of the complications was related to sternal wrapping,
      bleeding from the sternal edge, or sternal wound problems. CONCLUSIONS: Sternal
      wrapping showed a very low incidence and severity of sternal wound complications,
      with good prevention of sternal osteomyelitis. Hemostatic properties were
      satisfactory, with transfusion rates within an acceptable range.

PMID- 24570500
TI  - Preoperative pulmonary artery pressure and mortality after lung transplantation.
AB  - BACKGROUND: The purpose of this study was to determine the influence of changes
      in pulmonary artery pressure during the waiting period on survival after lung
      transplantation for pulmonary fibrosis. METHODS: We identified 65 patients with
      pulmonary fibrosis who underwent lung transplantation from 2003 to 2010.
      Pulmonary artery pressure determined at listing was compared with intraoperative
      pressure. The primary outcome was overall survival. Co-variates included type of
      transplantation (single or bilateral), ischemic time, recipient and donor age and
      sex. RESULTS: The median age of the 65 patients undergoing transplantation was 58
      years, and 27 (43%) underwent bilateral sequential transplantation. Twenty-two
      (35%) patients presented at transplantation with a mean pulmonary artery pressure
      increased by at least 10% compared to the initial pressure at the time of
      listing. Rising pulmonary artery pressure at transplantation was associated with
      increased mortality (p = 0.022). Other factors including type of operation,
      ischemic time, age, and sex, were not significantly associated with mortality.
      Post-transplantation survival was worse among recipients who had pulmonary artery
      pressure increased by at least 10% at transplantation (p = 0.003, logrank).
      CONCLUSIONS: Increasing pulmonary artery pressure while awaiting lung
      transplantation is associated with worse long-term survival following
      transplantation, and is a sign of progressively worsening disease for which
      greater urgency of donor organ allocation should be considered.

PMID- 24570501
TI  - Analysis of the sternum for sternal closure with bioabsorbable sternal pins.
AB  - PURPOSE: Poly-L-lactide sternal pins have been reported to be beneficial for
      sternal closure. However, we sometimes experience a small sternum, and the size
      characteristics of the sternum have not been fully investigated. We analyzed size
      features of the sternum to determine the optimal size of sternal pin for sternal
      closure. METHODS: Chest computed tomography scans were preoperatively obtained in
      144 patients undergoing major cardiovascular surgery. We reviewed all scans at
      the level of the sternum, and measured the width of the bone marrow of the
      sternum on each computed tomography slice. RESULTS: The mean values of bone
      marrow width of the sternal manubrium and body of male patients were
      significantly higher than those of females (manubrium: 38.6 +/- 3.9 mm in males,
      34.5 +/- 3.3 mm in females, p < 0.0001; body: 23.4 +/- 3.7 mm in males, 20.8 +/-
      2.8 mm in females, p < 0.0001). There was no correlation between the bone marrow
      width of the sternal body and body surface area in either males or females
      (males: r = 0.08, p = 0.45, females: r = 0.08, p = 0.58). CONCLUSION: To select
      the appropriate size of sternal pin, preoperative measurement of the bone marrow
      width of the sternum is recommended because it cannot be predicted from body
      size.

PMID- 24570502
TI  - Successful staged operation for acute type A aortic dissection with paraplegia.
AB  - A 75-year-old man presented with both paraplegia and acute occlusion of the
      abdominal aorta at onset. Extraanatomical bypass was performed following spinal
      drainage. After 3 days, the ascending aorta replaced under cardiopulmonary bypass
      using the extraanatomical bypass graft for arterial cannulation. The abdominal
      aorta was replaced after 6 months. A staged operation is one of the options for
      acute aortic dissection with paraplegia and acute occlusion of the abdominal
      aorta. 

PMID- 24570504
TI  - Early type II endoleak repair after endovascular therapy in Behcet's disease.
AB  - Vascular complications of Behcet's disease include occlusion of vessels and
      arterial aneurysm formation, which is prone to rupture. Early type II endoleak
      repair following an endovascular stent-graft procedure for a ruptured descending
      aortic aneurysm in a 31-year-old man with Behcet's disease is described.
      Endovascular stent-grafts provide an important alternative in complicated cases,
      but the possibility of endoleak should be born in mind. 

PMID- 24570503
TI  - Hemitruncus, septal defect, and anomalous coronary artery from pulmonary artery.
AB  - An 8-month-old boy with aortic origin of the right pulmonary artery, ventricular
      septal defect, and anomalous origin of the left main coronary artery from the
      right pulmonary artery, underwent uneventful single-stage surgical correction.
      The rarity and technical aspects of managing this condition are discussed. 

PMID- 24570505
TI  - Methemoglobinemia due to nitric oxide therapy in a child after cardiac surgery.
AB  - A 5-month-old boy with trisomy 21 had repair of ventricular septal defect, atrial
      septal defect, and ligation of a patent ductus arteriosus. Due to severe
      pulmonary hypertension, NO inhalation was instituted postoperatively. Over the
      course of next few hours, he developed life-threatening methemoglobinemia. The
      condition once recognized was corrected with exchange blood transfusion. The
      management strategy is described with a brief review of the literature. 

PMID- 24570506
TI  - Integrity of mechanical aortic valve prostheses explanted after 27 and 23 years.
AB  - We describe 2 cases of mechanical aortic valve endocarditis and the influence on
      clinical outcome and prostheses material integrity. One patient required
      extensive reconstruction due to active endocarditis leading to a "rocking valve".
      The second case was caused by late aortic dissection following endocarditis. Both
      valve prostheses showed remarkable material quality and performance in functional
      assessment and high resolution scanning electron microscopic evaluation after 27
      and 23 years of service. 

PMID- 24570507
TI  - Truncal valve repair using autologous pericardial patch augmentation.
AB  - A 35-month-old boy with severe truncal valve regurgitation underwent successful
      repair by tricuspidization using raphe slicing and an extension technique with
      glutaraldehyde-treated autologous pericardium. His truncal valve regurgitation
      improved from severe to mild 5 years postoperatively. Tricuspidization using
      raphe slicing and valve extension with autologous pericardium might be one of the
      alternatives for truncal valve regurgitation with a quadricuspid valve. 

PMID- 24570508
TI  - Right ventricular free wall intramyocardial hematoma after coronary bypass.
AB  - Intramyocardial dissecting hematoma is a rare form of incomplete cardiac rupture
      usually reported with reference to the left ventricle or interventricular septum.
      Here we report the case of a 64-year-old man with an isolated right ventricular
      dissecting intramyocardial hematoma following coronary artery bypass surgery. 

PMID- 24570509
TI  - Percutaneous coronary intervention in a case of afibrinogenemia.
AB  - Congenital afibrinogenemia is a rare autosomic recessive blood disorder. A 30
      year-old lady, known to have congenital afibrinogenemia, presented with acute
      anterior myocardial infarction. We managed her with dual antiplatelet therapy and
      atorvastatin, but her chest pain did not subside and she was transferred to the
      catheterization laboratory. A proximal left anterior descending artery occlusion
      was crossed with a floppy wire. Angioplasty was performed successfully with a
      bare metal stent, and her symptoms resolved completely. 

PMID- 24570510
TI  - Reconstruction of pulmonary venous conduit with CorMatrix in lung transplant.
AB  - Anomalous pulmonary vein anatomy is infrequently encountered during
      reconstructive lung surgery, especially lung transplantation. Complications of
      pulmonary venous anastomosis carry high morbidity and mortality. We report a case
      of anomalous pulmonary vein reconstruction with a decellularized porcine small
      intestinal submucosa-derived extracellular matrix during bilateral lung
      transplantation in an 18-year-old woman with cystic fibrosis. 

PMID- 24570511
TI  - Mucinous adenocarcinoma of trachea: a rare case of primary tracheal tumor.
AB  - A primary tracheal tumor is not common, but adenocarcinoma is particularly rare.
      We describe a case of primary tracheal mucinous adenocarcinoma misdiagnosed as
      asthma in a 17-year-old girl. Computed tomography revealed an intraluminal
      partially obstructing mass in the mid portion of the trachea. A sleeve resection
      of the involved trachea with primary anastomosis was performed, followed by
      adjuvant radiotherapy. After 23 months of follow-up, there has been no
      recurrence. 

PMID- 24570512
TI  - Expanding extrapleural hematoma from rib fractures after cardiac surgery.
AB  - A 79-year-old man underwent coronary artery bypass grafting and ascending aorta
      prosthetic replacement for aneurysm at our Institution. His postoperative course
      was characterized by rapid onset of hypotension and anemia. Re-exploration found
      no surgical source of bleeding. A chest computed tomography showed a huge
      extrapleural hematoma caused by rib fractures. Percutaneous chest drainage was
      effective, and the patient recovered quickly. Follow-up computed tomography
      confirmed a good result. 

PMID- 24570513
TI  - Mounier-Kuhn syndrome: a rare and dangerous condition.

PMID- 24570514
TI  - Retroperitoneal leiomyoma that infiltrated into the right ventricle.

PMID- 24570515
TI  - Metastasis in lung transplant after hepatic transplant for cholangiocarcinoma.

PMID- 24570516
TI  - Massive postpartum pneumomediastinum.

PMID- 24570518
TI  - Dr Thomas Bruce Ferguson: 6 May 1923-26 May 2013.

PMID- 24570519
TI  - Transcatheter aortic valve implantation: implications for Asian patients.
AB  - BACKGROUND: transcatheter aortic valve implantation is now an accepted therapy
      for patients with severe aortic valve stenosis who are deemed inoperable, and it
      is a reasonable alternative for patients with high surgical risk. This study
      assessed the clinical outcomes of this procedure and the implications of
      transcatheter aortic valve implantation for such patients. METHODS: 14
      consecutive patients with severe aortic valve stenosis, who underwent
      transcatheter aortic valve implantation, were assessed. Baseline clinical
      characteristics, procedural information, and clinical outcomes and complications
      were compared at baseline and at follow-up. Thirty-day mortality was also
      assessed. RESULTS: the mean age of the patients was 81 +/- 8 years (35% females).
      The mean Society of Thoracic Surgeons score was 6.8 +/- 3.7. Most patients had
      chronic kidney disease with an estimated glomerular filtration rate of 44.5 +/-
      14.9 mL.kg(-1).min(-1). The mean annulus diameter was 21.9 +/- 1.7 mm, and 8
      (57%) patients received 23-mm valves. After transcatheter aortic valve
      implantation, the mean transaortic gradient and aortic valve area improved from
      42.9 +/- 19.4 to 8.9 +/- 3.1 mm Hg (p < 0.001) and 0.7 +/- 0.1 to 1.5 +/- 0.3
      cm(2) (p < 0.001), respectively. The 30-day mortality for this cohort was 7%.
      CONCLUSION: transcatheter aortic valve implantation can be performed successfully
      in carefully selected Asian patients. The decision to undertake this procedure
      should be guided by the surgical team.

PMID- 24570520
TI  - Trends in coronary artery bypass surgery: impact on early outcomes.
AB  - BACKGROUND: improvements in nonsurgical revascularization have left a group of
      higher-risk patients presenting for operation in a later stage of coronary artery
      disease. We undertook this study to analyze temporal changes in demographic and
      clinical profiles and outcomes of cardiac surgical patients. METHODS: we
      identified and retrieved preoperative, intraoperative, and postoperative
      variables for 3064 consecutive patients who underwent myocardial
      revascularization at the Aga Khan University Hospital between 2006 and 2011.
      Mortality and morbidity outcomes were compared using univariate and multivariate
      analyses. RESULTS: mean age, prevalence of left ventricular systolic dysfunction,
      unstable angina, mean number of occluded vessels, and arrhythmias at presentation
      increased steadily over time. The prevalence of diabetes, chronic lung disease,
      peripheral vascular disease, prior stroke, prior myocardial infarction, and left
      main disease declined. Operative mortality did not change significantly (3.5% vs.
      3.8%, p = 0.512). Determinants of operative mortality included older age, female
      sex, renal insufficiency, left ventricular systolic dysfunction, and longer
      bypass and crossclamp times. CONCLUSION: coronary operations are increasingly
      performed in higher-risk patients with greater comorbidities. Despite this,
      operative mortality has not increased.

PMID- 24570521
TI  - Does removal of steel wires relieve post-sternotomy pain after cardiac surgery?
AB  - BACKGROUND: Post-sternotomy pain in the absence of cardiac ischemia and sternal
      instability is most commonly due to the sternal wire sutures or a protruding
      wire. We performed a retrospective study to investigate the effect of removal of
      the steel wires for relief of post-sternotomy pain. METHODS: All 206 patients who
      underwent sternal wire removal in our institution from January 2003 through
      August 2011 were included in this study. Alive patients were contacted by
      telephone to inquire about the fate of their pain. Accordingly, patients were
      classified into 4 groups: group 1 were free of symptoms; group 2 were satisfied,
      significantly better than before wire removal; group 3 had unchanged symptoms;
      and group 4 had worsening of pain after wire removal. RESULTS: After excluding
      patients who died during the follow-up and those who had sternal instability and
      wound infection, 186 patients were available for the questionnaire. Complete
      relief of pain occurred in 83% of these patients, and 10% had improvement of
      their symptoms. CONCLUSIONS: We recommend removal of the steel wires in patients
      with persistent chest pain after median sternotomy, when sternal instability,
      mediastinitis, and cardiac causes such as ischemia are excluded.

PMID- 24570522
TI  - Minimally invasive pediatric surgery in uncomplicated congenital heart disease.
AB  - BACKGROUND: We aimed to highlight the use of a minimally invasive approach in
      uncomplicated congenital heart surgery. PATIENTS AND METHODS: We investigated
      retrospectively 32 children below 10 years of age who underwent elective closure
      of ostium secundum type (n = 27), sinus venosus type (n = 4) and ostium primum
      type (n = 1) atrial septal defects through a limited skin incision and partial
      lower sternotomy between August 2001 and December 2008. All patients had
      cannulation through the same incision for cardiopulmonary bypass. RESULTS: A
      pericardial patch was used to close the defect in 8 patients and direct suturing
      in 24. The mean time from the skin incision to cannulation was 56 +/- 23 min.
      Total bypass time was 27 +/- 12 min, and crossclamp time was 15 +/- 8 min. Mean
      length of hospital stay was 4 +/- 2 days. We did not encounter any complications
      or mortality. CONCLUSIONS: A minimally invasive approach, consisting of a limited
      skin incision and partial lower sternotomy, is a safe, reliable, and cosmetically
      advantageous method in uncomplicated congenital heart disease surgery, which can
      be performed widely, and may replace the standard approach without increasing
      mortality and morbidity.

PMID- 24570523
TI  - Magnetic resonance angiography vs. angiography in tetralogy of Fallot.
AB  - AIM: : To determine whether gadolinium-enhanced three-dimensional magnetic
      resonance angiography can provide a noninvasive alternative to diagnostic
      catheterization for evaluation of pulmonary artery anatomy in tetralogy of
      Fallot. PATIENTS AND METHODS: Thirty-five consecutive patients with tetralogy of
      Fallot, who attended the cardiology outpatient department between January 2008
      and December 2009, were included in the study. There were 21 males and 14
      females, with a mean age of 9 +/- 4.15 years (range, 3-21 years). Thirty-two
      patients had tetralogy of Fallot with varying severities of valvular and
      infundibular stenosis. Three patients had tetralogy of Fallot with pulmonary
      atresia. All patients underwent both cardiac catheterization with X-ray
      angiography and 3-dimensional magnetic resonance angiography within one month.
      RESULTS: Measurements of right and left pulmonary arteries and aortopulmonary
      collaterals were equal by both methods. There was a good correlation between
      magnetic resonance angiography and catheterization measurements of branch
      pulmonary arteries. CONCLUSION: Gadolinium-enhanced three-dimensional magnetic
      resonance angiography can be used as a reliable noninvasive alternative to X-ray
      cineangiography for delineation of pulmonary arterial anatomy in sick infants and
      young children, obviating the need for catheterization.

PMID- 24570524
TI  - Estimation of serum neopterin in patients with acute coronary syndrome.
AB  - BACKGROUND: The aim of our study was to determine neopterin levels in patients
      with acute coronary syndrome, in which the release of various cytokines activates
      the cellular immune system. There is an increase in the number and activity of T
      cells in unstable atherosclerotic plaques, and of type 1 helper T-cells that
      produce interferon gamma, which in turn produces neopterin, a byproduct of the
      guanosine triphosphate-biopterin pathway and a marker for activated macrophages.
      METHODS: We studied 600 subjects consisting of healthy volunteers and patients
      with noncardiac chest pain, ST-segment elevation myocardial infarction, non-ST
      segment elevation myocardial infarction, or unstable angina. Neopterin levels
      were determined by high-performance liquid chromatography. RESULTS: Mean serum
      neopterin levels in ST-segment elevation myocardial infarction (11.5 +/- 3.2
      nmol.L(-1)), non-ST-segment elevation myocardial infarction (9.8 +/- 2.9 nmol.L(
      1)), and unstable angina patients (9.4 +/- 2.3 nmol.L(-1)) were significantly
      higher than those in noncardiac chest pain patients (7.4 +/- 1.9 nmol.L(-1)) and
      healthy volunteers (7.2 +/- 0.6 nmol.L(-1); p < 0.001). CONCLUSION: These
      findings suggest that serum neopterin levels may be a useful marker of systemic
      inflammation, and measurement of serum neopterin may be helpful in assessing the
      risk of developing coronary heart disease.

PMID- 24570525
TI  - What outcome after the prescription of neoadjuvant chemotherapy in lung cancer?
AB  - BACKGROUND: The treatment of patients with locally advanced non-small-cell lung
      cancer is controversial. Surgery remains the gold standard, even in this group.
      Neoadjuvant chemotherapy could allow surgical resection in patients initially
      judged inoperable. METHODS: From January 2009 to May 2010, neoadjuvant
      chemotherapy was indicated in 27 patients with NSCLC (25 men, 2 women). Their
      mean age was 65 years. The stages were: IIB in 5, IIIA in 17 (6 in stage IIIAN2),
      IIIB in 2, and IV in 3. RESULTS: 23 patients received neoadjuvant chemotherapy, 2
      refused induction treatment, and 2 had impaired status. The neoadjuvant
      chemotherapy regimen was gemcitabine-cisplatin in 17 patients and vinorelbine
      cisplatin in 6. Only 5 patients underwent complete surgical treatment after
      induction: 1 in stage IIB, 1 in stage IIIAN0, 1 in IIIB, and 2 in stage IV (1
      operated brain metastasis, and 1 operated adrenal metastasis). Surgical treatment
      was not achieved after neoadjuvant chemotherapy in 18 patients because of
      progressive disease. CONCLUSION: Neoadjuvant chemotherapy offers several
      potential benefits, but it may delay surgery or eliminate eligibility as a
      surgical candidate. Rigorous patient selection for this type of multimodal
      treatment is essential.

PMID- 24570526
TI  - Pulmonary metastasectomy and repeat metastasectomy for soft-tissue sarcoma.
AB  - BACKGROUND: For patients with lung metastases from soft-tissue sarcoma, pulmonary
      metastasectomy is considered to be the only chance of possible cure. In this
      survey, we analyzed some potential prognostic factors affecting the outcome in
      these patients. PATIENTS AND METHODS: 34 patients who underwent pulmonary
      metastasectomy for soft-tissue sarcoma from April 1996 to April 2007, were
      enrolled in our study. The median follow-up period was 26 months. Survival
      curves, factors affecting the outcome, and treatment success rate were evaluated.
      RESULTS: Complete resection was achieved in 88.2% of patients. There was no
      perioperative mortality. The median overall survival and median disease-free
      survival were 42 and 27 months, respectively. Incomplete resection and bilateral
      lung metastases had significant adverse effects on overall survival. Shorter
      disease-free interval (<18 months) was a significant predictor of survival on
      multivariate analysis. Metastasectomy was attempted in 12 cases of whom 50%
      remained disease-free to the end of follow-up. CONCLUSION: Complete resection is
      the most important defining factor of success rate and survival. Patients with
      bilateral lung metastases or a shorter disease-free interval have significantly
      lower success rates. Repeat metastasectomy is curative in many patients.

PMID- 24570527
TI  - The role of thoracoscopic debridement in the treatment of parapneumonic empyema.
AB  - AIM: To evaluate the efficacy of early video-assisted thoracoscopic debridement
      in patients with the fibropurulent phase of parapneumonic empyema. PATIENTS AND
      METHODS: 40 patients with parapneumonic empyema resistant to 2 weeks of
      antibiotic therapy, were randomly divided into 2 groups. In group 1 (20
      patients), antibiotic therapy and irrigation was continued, and in group 2 (20
      patients), video-assisted thoracoscopic debridement was performed. The 2 groups
      were compared in terms of therapeutic results. RESULTS: The male/female ratio was
      29/11. Group 1 included 16 men and 4 women with a mean age of 54 years, and mean
      hospital stay was 41 days. Group 2 consisted of 14 men and 6 women with a mean
      age of 51 years, and mean hospital stay was 23 days. Considering the therapeutic
      results, 12 patients in group 1 were cured by antibiotic therapy and irrigation,
      whereas 8 required decortication and pleurectomy with thoracotomy. In group 2, 18
      patients were cured by video-assisted thoracoscopic debridement, and 2 underwent
      thoracotomy and decortication due to intraoperative bleeding. A significant
      difference in therapeutic results was noted between the groups (p = 0.028).
      CONCLUSION: Video-assisted thoracoscopic debridement provides a high success rate
      and less invasive treatment for the early stages of empyema.

PMID- 24570528
TI  - Repair of right ventricle rupture caused by left coronary artery occlusion.
AB  - A 67-year-old man was admitted with right ventricular free wall rupture secondary
      to occlusion of the left anterior descending artery. Emergency coronary
      angiography showed total occlusion of the proximal left anterior descending
      artery and severe stenosis of the proximal right coronary artery.
      Echocardiography revealed acute cardiac tamponade, and free wall rupture of the
      heart was suspected. At surgery under cardiopulmonary bypass, closure was
      achieved using mattress sutures with pledgets. 

PMID- 24570530
TI  - Chronic total occlusion of left main coronary artery in a young man.
AB  - Chronic total occlusion of the left main coronary artery is rarely encountered in
      coronary angiography. Patients are at high risk of death because of its intimate
      association with massive anterior myocardial infarction. A 29-year-old man with
      no cardiac risk factors, presented with myocardial infarction and severe mitral
      regurgitation. Coronary angiography revealed chronic total occlusion of the left
      main coronary artery. He underwent coronary artery bypass grafting and mitral
      valve repair. 

PMID- 24570529
TI  - Recurrent giant sinus of Valsalva aneurysm and ankylosing spondylitis.
AB  - A 48-year-old woman underwent aneurysmectomy and primary suture repair with a
      pericardial patch for sinus of Valsalva aneurysm secondary to ankylosing
      spondylitis. The sinus of Valsalva aneurysm recurred one year after surgery, and
      reached a diameter of 53 mm. Special attention must be paid to the potential
      relapse of aortic aneurysms that develop secondary to autoimmune disorders, when
      using primary suture or patch repair. 

PMID- 24570531
TI  - Systolic anterior motion of mitral valve with calcified annulus in octogenarians.
AB  - Systolic anterior motion of the mitral leaflet causing left ventricular outflow
      tract obstruction is commonly seen in hypertrophic cardiomyopathy and also in
      patients with advanced mitral valve disease with excessive anterior leaflet
      tissue or a reduced aortic-mitral angle. We describe 2 octogenarians who
      presented with systolic mitral leaflet anterior motion in advanced mitral valve
      disease with severe mitral annular calcification and associated asymmetrical
      septal hypertrophy. 

PMID- 24570532
TI  - Pulmonary atresia with ventricular septal defect and pulmonary sequestration.
AB  - A 5-day-old girl who had pulmonary atresia with ventricular septal defect, patent
      ductus arteriosus, intralobar pulmonary sequestration of the right lower lobe,
      and retroesophageal innominate vein, was referred to our institution. We
      successfully performed a systemic-to-pulmonary shunt. During cardiopulmonary
      bypass, the arteries supplying the sequestrated lung were ligated above the
      diaphragm through the median sternotomy, without a thoracotomy. The postoperative
      course was uneventful, and we avoided the potential complications of lung
      infection and ventricular overload. 

PMID- 24570533
TI  - Tetralogy of Fallot with pheochromocytoma: an unusual therapeutic challenge.
AB  - An adult with unoperated tetralogy of Fallot diagnosed simultaneously with
      pheochromocytoma is extremely rare. This poses obvious diagnostic and therapeutic
      challenges. A 29-year-old woman with these conditions was successfully operated
      on for both diseases in the same hospitalization. There is some interesting
      speculation regarding the association of pheochromocytoma with uncorrected
      cyanotic congenital heart disease. 

PMID- 24570534
TI  - Thrombi migration to atrium diagnosed by transesophageal echocardiography.
AB  - Two days before surgery in a 70-year-old man with renal cell carcinoma,
      transthoracic echocardiography showed a dense mass in the inferior vena cava,
      lying proximally, but no mass was observed in the right atrium. Intraoperative
      transesophageal echocardiography revealed unexpected tumor thrombi in the right
      atrium, and the surgical plan was changed. This case highlights the importance of
      intraoperative transesophageal echocardiography in patients with renal cell
      carcinoma. 

PMID- 24570535
TI  - Double patch repair for a double ventricular rupture.
AB  - We describe the case of a 77-year-old woman with recent acute myocardial
      infarction complicated by ventricular septal defect and formation of a
      pseudoaneurysm, which were successfully treated surgically with a double patch
      repair. This case highlights the importance of early recognition of this serious
      complication, using clinical and echocardiographic examinations, and the various
      challenges encountered in surgical repair. 

PMID- 24570536
TI  - Off-pump coronary artery bypass in congenital absence of pericardium.
AB  - Off-pump coronary artery bypass involves precise manipulations for proper
      positioning the heart without causing hemodynamic compromise. Pericardial stay
      sutures exerting appropriate traction play an important role in off-pump surgery.
      We report a rare case in which a congenital pericardial defect was discovered
      after sternotomy in a patient undergoing off-pump coronary artery bypass. 

PMID- 24570537
TI  - Resection of an intrapericardial paraganglioma under cardiopulmonary bypass.
AB  - We describe the case of a 52-year-old woman with a non-functional middle
      mediastinal paraganglioma. Radiologic diagnosis of paraganglioma was confirmed by
      multidetector computed tomography and (18)F-fluorodeoxyglucose positron-emission
      tomography, without biopsy. Surgical resection was performed via a median
      sternotomy, and cardiopulmonary bypass was required for complete resection of the
      tumor because of invasion to the intrapericardial pulmonary artery. Preoperative
      pathological diagnosis of mediastinal paraganglioma by biopsy is dangerous due to
      bleeding, and should be avoided. 

PMID- 24570538
TI  - A case of coelomic cysts of the mediastinum.
AB  - Coelomic cysts are rare cysts of mesothelial origin. They are generally
      unilocular and can develop in various sites. We describe a case of a multicystic
      lesion discovered incidentally in the anterior mediastinum of a 41-year-old man.
      Immunohistochemistry confirmed multiple coelomic cysts of the mediastinum. 

PMID- 24570539
TI  - Pneumonectomy after response to gefitinib treatment for lung adenocarcinoma.
AB  - A 69-year-old Japanese woman who had never smoked had lung adenocarcinoma
      harboring epidermal growth factor receptor mutation. After 8 months of gefitinib
      treatment, salvage pneumonectomy was performed. Microscopic examination showed
      that non-responsive adenocarcinoma remained although necrosis was prominent.
      Postoperatively, the patient developed empyema that was successfully managed. The
      postoperative empyema after treatment with gefitinib should be noted, as well as
      the finding that residual viable tumor cells remained even after the dramatic
      radiographic response. 

PMID- 24570540
TI  - Echinococcosis, bilateral pulmonary complicated and non complicated with
      bilateral thyroid gland.

PMID- 24570541
TI  - Translocation of dehisced aortic prosthesis to left ventricular outflow tract.

PMID- 24570542
TI  - Right heart overload due to pulmonary trunk obstruction after Bentall procedure.

PMID- 24570543
TI  - Cavernous hemangioma of the first rib.

PMID- 24570544
TI  - Diffuse mural thrombus in a patient with thoracic aortic aneurysm.

PMID- 24570545
TI  - Solitary malignant fibrous tumor of the mediastinum.

PMID- 24570546
TI  - Mediastinal drainage in descending necrotizing mediastinitis.
AB  - Descending necrotizing mediastinitis has been thoroughly described in the past,
      but we could not find a detailed description of the technique to perform adequate
      drainage and lavage of all the mediastinal and thoracic spaces. We describe the
      procedure as we perform it, emphasizing the sites for incision and proper
      drainage of all the mediastinal compartments and the contralateral thoracic
      cavity. 

PMID- 24570547
TI  - A "giant" complication at an early age: an unusual cause of cardiac tamponade.

PMID- 24570548
TI  - One-way endobronchial valve for bronchopleural fistula after necrotizing
      pneumonia.

PMID- 24570549
TI  - Chronic tension empyema or chronic expanding empyema?

PMID- 24570550
TI  - Chronic tension empyema or chronic expanding empyema? Authors' response.

PMID- 24570551
TI  - RETRACTION: Thrombus arising from the ascending aorta', Manabu Shiraishi, Kei
      Aizawa, Shin-ichi Ohki and Yoshio Misawa.
AB  - The paper entitled 'Thrombus arising from the ascending aorta' by Manabu
      Shiraishi, Kei Aizawa, Shin-ichi Ohki and Yoshio Misawa published in Asian
      Cardiovasc Thorac Ann 2012; 20: 351, doi: 10.1177/0218492311419767 has been
      retracted. This is due to duplicate publication. An earlier version of the
      article was found to have been previously published in Eur J Cardiothorac Surg
      (2011) 40(3): e133, doi: 10.1016/j.ejcts.2011.04.032. 

PMID- 24570552
TI  - Extracorporeal membrane oxygenation in adults: experience from the Middle East.
AB  - BACKGROUND: The literature reports conflicting results for survival after
      extracorporeal membrane oxygenator support, and survival differs in pediatric and
      adult patients. We present our institutional experience of adult extracorporeal
      membrane oxygenator support. METHODS: From January 2007 to December 2009, 19
      adult patients required extracorporeal membrane oxygenator support after cardiac
      surgery or catheter interventions. It was provided on an emergency basis to 11
      patients, urgently to 5, and electively to 3. Indications included post
      cardiotomy cardiogenic shock, post-cardiotomy acute respiratory failure,
      emergency cardiac resuscitation, and post-percutaneous coronary intervention
      cardiogenic shock. The mean duration of support was 4 days (range, 1-11 days).
      RESULTS: Seven (36.84%) patients could be weaned off extracorporeal membrane
      oxygenator support; one (14.28%) of them survived to hospital discharge and the
      other 6 (85.71%) died in hospital. Twelve (63.15%) patients could not be weaned
      off and died while still on extracorporeal membrane oxygenator support. Overall
      30-day hospital mortality was 94.73%, and survival to discharge was 5.26%.
      CONCLUSION: Our institutional experience of extracorporeal membrane oxygenator
      support for cardiac indications in adult patients indicates poor survival. It
      significantly increased costs by delaying imminent death and prolonging stay in
      the intensive care unit.

PMID- 24570553
TI  - Treatment of left anterior descending coronary artery stenosis: stent or surgery.
AB  - BACKGROUND: Drug-eluting stents have emerged as a solution to the problem of
      restenosis after bare-metal stent implantation, as an alternative to off-pump
      coronary bypass, for isolated left anterior descending coronary artery lesions at
      short-term follow-up. However, long-term follow-up is yet to be defined. METHODS:
      From January to December 2004, 64 consecutive patients underwent myocardial
      revascularization: 31 by drug-eluting stents and 33 by off-pump coronary bypass.
      The primary endpoint was angiographic outcome, and the secondary endpoint was
      clinical outcome at 5 years. RESULTS: There was no early or late mortality in
      either group. Hospital stay was significantly shorter in the stent group (2.5 +/-
      2.1 vs. 7.1 +/- 4.9 days, p = 0.003). Long-term patency was higher and major
      adverse cardiac events (recurrence of angina and revascularization of target
      vessel) were encountered less frequently in the coronary bypass group, although
      not significantly. CONCLUSION: The 5-year follow-up showed no significant
      difference between the off-pump coronary bypass and stent groups for the primary
      and secondary endpoints. As a significant difference between treatment options is
      lacking, decision-making for appropriate treatment in this group of patients
      requires the collaboration of cardiologists and cardiovascular surgeons and an
      individual approach, to achieve successful long-term outcomes.

PMID- 24570554
TI  - Determinants of renal replacement therapy after adult cardiac surgery.
AB  - BACKGROUND: Acute renal injury requiring renal replacement therapy after cardiac
      surgery develops in 1%-5% of patients, and is strongly associated with
      perioperative morbidity and mortality. The prognostic risk factors for
      development acute renal injury requiring renal replacement therapy are identified
      in this study. METHODS: 2585 adult patients who underwent cardiac surgery during
      a 1-year period (November 2010 to October 2011) were studied. The patients who
      developed acute renal injury requiring renal replacement therapy were compared
      with matched controls. Logistic regression analysis was applied to determine the
      predictors of acute renal injury requiring renal replacement therapy. RESULTS: 44
      patients developed acute renal injury requiring renal replacement therapy
      following cardiac surgery. On multivariate logistic analysis, the following
      factors independently predicted acute renal injury requiring renal replacement
      therapy (p < 0.05): preoperative critical state, pre-existing renal dysfunction,
      preoperative diastolic dysfunction, and combined cardiac surgery. CONCLUSION: The
      risk of acute renal injury requiring renal replacement therapy can be fairly
      accurately predicted and quantified on the basis of available preoperative and
      intraoperative data. These predictors may be used by physicians to estimate the
      risk and target high-risk groups for interventions that prevent, reduce, or
      ameliorate the occurrence of renal failure needing acute renal replacement
      therapy.

PMID- 24570555
TI  - Post-infarction ventricular septal defect: surgical outcomes in the last decade.
AB  - BACKGROUND: Post-infarction ventricular septal defects require surgical closure.
      Only a few studies have been conducted in Asian populations. This study reports
      the current outcomes and determinants affecting survival. METHODS: Between
      January 1995 and January 2012, 40 patients underwent surgery for post-infarction
      ventricular septal defect. We analyzed demographics, clinical, angiographic, and
      echocardiographic parameters, operative data, postoperative morbidity, and
      survival. Mean follow-up was 5.2 +/- 5.3 years. Univariate and multivariate
      analyses were used to determine the factors affecting 30-day mortality and long
      term survival. RESULTS: There was no intraoperative death. Our 30-day mortality
      was 20%. Single-vessel disease was found on coronary angiography in 63% of
      patients. Eight patients had concomitant coronary artery bypass grafting. Overall
      survival at 1, 5, and 10 years was 68%, 55%, and 42%, respectively. Event-free
      survival from subsequent angina, myocardial infarction, congestive heart failure,
      or percutaneous interventions at 1, 5, and 10 years was 66%, 43%, and 25%,
      respectively. Preoperative oliguria and postoperative sepsis were independent
      predictors of 30-days mortality on multivariate analysis (p = 0.02). Preoperative
      left ventricular function was associated with long-term survival (p = 0.048).
      CONCLUSION: We had good results of current postinfarction ventricular septal
      defect repair. Selected patients had concomitant coronary artery bypass grafting.
      Preoperative oliguria and postoperative sepsis were independent predictors of 30
      day mortality, while left ventricular function was related to long-term survival.

PMID- 24570556
TI  - External carotid-to-subclavian artery bypass in stent grafting of thoracic aorta.
AB  - BACKGROUND: A bypass between the left common carotid artery and the left
      subclavian artery has been made in some patients undergoing thoracic endovascular
      aortic repair that covers the orifice of the left subclavian artery. However,
      complications associated with temporary occlusion of the left common carotid
      artery are reportedly not uncommon. METHODS: Between January 2009 and September
      2011, left external carotid-to-left subclavian artery bypass was made using a
      polytetrafluoroethylene graft in 15 patients undergoing a thoracic endovascular
      aortic repair that covered the orifice of the left subclavian artery. Adverse
      effects associated with the procedure were assessed, and patency of the bypass
      graft was determined by contrast-enhanced computed tomography before discharge
      and at least once during follow-up. RESULTS: All patients were discharged without
      any brain complications. All 15 bypass grafts were patent prior to discharge and
      during the follow-up period. One patient suffered temporary left recurrent
      laryngeal nerve palsy postoperatively. No other sequelae were associated with
      left external carotid-to-left subclavian artery bypass. CONCLUSION: Left external
      carotid-to-left subclavian artery bypass is a promising procedure in patients
      undergoing thoracic endovascular aortic repair that covers the orifice of the
      left subclavian artery.

PMID- 24570557
TI  - Ventricular tachyarrhythmia after coronary bypass surgery: incidence and outcome.
AB  - BACKGROUND: Ventricular tachyarrhythmia after coronary artery bypass graft is
      common and the occurrence has been described, but the incidence and risk factors
      are not well defined. AIM: To evaluate the incidence of arrhythmias and to detect
      high-risk populations. METHODS: In this prospective study, 856 consecutive
      patients undergoing coronary artery bypass graft were monitored for new-onset
      ventricular tachyarrhythmias: non-sustained monomorphic ventricular
      tachyarrhythmia, sustained monomorphic ventricular tachyarrhythmia, sustained
      polymorphic ventricular tachyarrhythmia, and ventricular fibrillation. Detailed
      analyses of the clinical, demographic, echocardiographic, and surgical findings
      and arrhythmias occurrence was carried out during 6 months of follow-up. RESULTS:
      The incidence of ventricular tachyarrhythmia was 26.6% (17.6% non-sustained
      monomorphic ventricular tachycardia, 5.5% sustained monomorphic ventricular
      tachycardia, 0.8% sustained polymorphic ventricular tachycardia, and 2.7%
      ventricular fibrillation). The strongest degrees of statistical significance were
      for low ejection fraction (p = 0.01) and ischemic heart disease (p = 0.02). The
      incidence of ventricular fibrillation (61%) was greatest in the first 48 h after
      surgery. Postoperative myocardial infarction (p = 0.03) and hemodynamic
      instability (p = 0.05) were also predictors of arrhythmia occurrence. Recurrence
      of arrhythmia was highest in the ventricular fibrillation group (52%). The
      correlations between tachyarrhythmia, age, sex, electrolyte disorders, body mass
      index, and systemic or pulmonary hypertension were not significant. CONCLUSION:
      In view of the strong relationship between ventricular arrhythmias and low
      ejection fraction, ischemic heart disease, coronary artery disease severity,
      postoperative myocardial infection, and hemodynamic impairment, continuous
      monitoring is necessary, especially in the first 48 h after coronary artery
      bypass surgery.

PMID- 24570558
TI  - Cardiac echinococcosis.
AB  - OBJECTIVE: Cardiac echinococcosis is an extremely rare disease, seen worldwide.
      Some clinical characteristics are unknown, and treatment modalities are unclear.
      METHODS: 41 patients diagnosed with cardiac or pericardial echinococcosis
      underwent surgery. We evaluated the patients echocardiographically in 8 different
      categories: cardiac echinococcosis lesions located within the heart, imaging
      appearance of each lesion, activity of the cysts, mode of cardiac echinococcosis,
      and number of cardiac lesions per patient. The surgical technique was reevaluated
      according to the intraoperative echocardiographic findings, especially according
      to the mode of the lesion. RESULTS: The hydatid cysts were located in the
      ventricular wall in 34 cases, the right atrium in 2, the noncoronary sinus
      Valsalva of the aorta in 1, between the aorta and the pulmonary bifurcation in 1,
      and in the pericardium alone in 4 cases. In 1 case, septal rupture occurred and
      the patient died. Relapse was seen in 1 patient who was operated on due to
      multiple ventricular and pericardial cysts; this patient underwent a second
      operation 6 years and 8 months after the initial surgery. CONCLUSION: Recent
      echocardiographic developments and application of intraoperative echocardiography
      enables a detailed classification for extirpation, and allows successful
      treatment.

PMID- 24570559
TI  - Wedge resection verses lobectomy for stage 1 non-small-cell lung cancer.
AB  - BACKGROUND: Lobectomy remains the gold standard with regard to potentially
      curative resection of non-small-cell lung carcinoma. We aimed to investigate
      whether there is a survival difference in stage 1 non-small-cell lung cancer
      patients who undergo lobectomy compared to a wedge resection. METHODS: We
      retrospectively analyzed a prospective database of 1283 patients who had
      potentially curative resection for stage 1 non-small-cell lung cancer. Only
      patients with adenocarcinoma, squamous or adenosquamous carcinoma were included.
      We benchmarked our 5-year survival against the 6th International Association for
      the Study of Lung Cancer results. Three techniques were used to assess the effect
      of a lobectomy compared to a wedge resection with regard to long-term survival:
      Cox multivariate regression analysis, neuronal network analysis, and propensity
      matching. RESULTS: Benchmarking failed to reveal any significant difference
      compared to the 6th International Association for the Study of Lung Cancer
      results. Crude analysis demonstrated superiority of lobectomy compared to wedge
      resection, p = 0.02. Cox regression analysis confirmed that age, body mass index,
      female sex, being a current smoker, tumor diameter, and preoperative forced
      expiratory volume in 1 s were all significant factors determining long-term
      survival. Wedge resection was not a significant factor. Neuronal network analysis
      concurred with the Cox regression analysis. Propensity matching with 1:1 matching
      demonstrated that wedge resections was not inferior to a lobectomy, p = 0.10.
      CONCLUSIONS: Cox regression analysis, neuronal network analysis, and propensity
      matching in stage 1 non-small-cell lung cancer demonstrate no difference in long
      term survival after wedge resection compared to lobectomy.

PMID- 24570560
TI  - Long-term survival after pneumonectomy for non-small-cell lung cancer.
AB  - OBJECTIVE: to investigate long-term survival in patients who underwent
      pneumonectomy for non-small-cell lung cancer at the University of Kentucky
      Medical Center. METHODS: we retrospectively reviewed 100 consecutive
      pneumonectomy cases from 1998 to 2009 at the University of Kentucky. We were able
      to obtain follow-up data on 99 of 100 patients. RESULTS: overall 1-, 2-, and 5
      year survival was 66%, 48%, and 32%, respectively. The 1-, 2-, and 5- survival
      for left pneumonectomy was 76%, 55%, and 40%, respectively, compared to 56%, 44%,
      and 22%, respectively, for right pneumonectomy. The median survival for left
      pneumonectomy was 2.4 years compared to 1.2 years for right pneumonectomy (p =
      0.056). The 5-year survival for patients diagnosed with stage I disease was 34%,
      compared to 19% for stage II disease, and 38% for stage III disease. The 5-year
      survival for patients who underwent neoadjuvant therapy was 31% compared to 39%
      for patients who received adjuvant therapy and 29% for patients who received
      surgery alone. These results were also not statistically significant. CONCLUSION:
      neoadjuvant therapy did not adversely affect long-term survival in our study.
      When compared to left pneumonectomy, right pneumonectomy for non-small-cell lung
      cancer is associated with adverse postoperative outcomes as well as poorer long
      term survival.

PMID- 24570561
TI  - Chest wall deformity found in patients with primary spontaneous pneumothorax.
AB  - BACKGROUND: the current consensus is that primary spontaneous pneumothorax
      frequently occurs in young male patients who are tall and thin. However, upon
      careful observation, many chest wall deformities have been recognized in primary
      spontaneous pneumothorax patients. We investigated the distinctive features of
      the chest wall configuration of primary spontaneous pneumothorax patients by
      comparing them with controls (normal and Marfan syndrome patients). METHODS: the
      anteroposterior and transverse diameters of the bilateral hemithoraxes of each
      patient at predetermined levels were measured by computed tomography. The
      asymmetry, which was based on the right/left anteroposterior and right/left
      transverse diameter ratio, and thickness based on the anteroposterior/transverse
      ratio, were examined. RESULTS: severe anteroposterior asymmetry and transverse
      asymmetry were observed in Marfan syndrome patients, and moderate anteroposterior
      asymmetry and transverse asymmetry were observed in primary spontaneous
      pneumothorax patients in comparison with normal control patients. Primary
      spontaneous pneumothorax and Marfan patients showed flatter thoraxes than normal
      control patients. CONCLUSIONS: primary spontaneous pneumothorax patients tend to
      have asymmetric and flat thoraxes. Subclinical thoracic wall deformity observed
      in the primary spontaneous pneumothorax group may partly contribute to alveolar
      pressure heterogeneity, and may be related to subpleural bleb formation.

PMID- 24570563
TI  - Case of single right atrial diverticulum and review of etiology and management.
AB  - Single diverticulum of the right atrium is an exceedingly rare congenital
      malformation. We describe successful surgical resection in a 22-year-old
      asymptomatic woman with single right atrial diverticulum. An attempt is also made
      to throw light on the etiology and management of this disease entity. 

PMID- 24570562
TI  - Two cases of chylopericardium after aortic valve surgery.
AB  - Chylopericardium is a rare clinical condition. It is largely idiopathic but could
      be iatrogenic from breached thoracic duct collaterals or secondary to thoracic
      duct flow obstruction. We describe 2 patients seen in a single cardiothoracic
      center within 6 weeks, and detail the clinicopathologic correlation of an unusual
      complication of cardiac surgery, as well as provide an algorithm for the
      diagnosis and management of postcardiotomy pericardial chylous effusion. 

PMID- 24570564
TI  - Combined approach in ventricular septal defect and adult pulmonary hypertension.
AB  - Early closure of a large ventricular septal defect before the onset of elevated
      pulmonary vascular resistance is important. Pulmonary hypertensive events might
      cause significant morbidity or mortality, even when closure is performed after
      infancy. Therefore, treatment of pulmonary hypertension after surgery may be the
      most important issue affecting the prognosis. We describe successful treatment of
      pulmonary hypertension in a 25-year-old woman after closure of large ventricular
      septal defect, with inhaled nitric oxide, sildenafil, and bosentan. 

PMID- 24570565
TI  - Use of subclavian steal in treating chronic total subclavian artery occlusion.
AB  - Endovascular treatment is a well-established option for subclavian artery
      stenosis. However, total occlusion of the proximal subclavian artery remains a
      challenge, posing difficulties of nonvisualization of distal vessels, access site
      issues, and deployment of vertebral embolism protection devices. A 65-year-old
      man with chronic total occlusion of the ostial left subclavian artery, underwent
      successful endovascular stenting in which the subclavian steal phenomenon was
      utilized as a roadmap to cross the occlusion. 

PMID- 24570566
TI  - Surgery for left ventricular pseudoaneurysm: thoracotomy or sternotomy.
AB  - We experienced 2 cases of left ventricular pseudoaneurysm located at the
      posterolateral wall. Case 1 was an 80-year-old woman who developed a left
      ventricular pseudoaneurysm 4 months after sutureless repair of left ventricular
      free wall rupture due to acute myocardial infarction. The pseudoaneurysm was
      repaired through a left thoracotomy. Case 2 was a 77-year-old woman who was
      diagnosed with left ventricular pseudoaneurysm incidentally by computed
      tomography. Aneurysmorrhaphy was conducted through a standard median sternotomy. 

PMID- 24570567
TI  - Corpus callosum hemorrhage during left ventricular-assist device support.
AB  - Patients supported by left ventricular-assist devices are at high risk of
      bleeding, but among the numerous hemorrhagic complications, those involving the
      corpus callosum are very uncommon. We report the case of a 35-year-old woman who
      suddenly experienced neurological symptoms 4 months after HeartMate II
      implantation. Cranial computed tomography showed a voluminous hematoma involving
      the corpus callosum. 

PMID- 24570568
TI  - Enlarged coronary artery pseudoaneurysm after drug-eluting stent implantation.
AB  - A 73-year-old man with 2-vessel coronary artery disease underwent a staged
      percutaneous coronary intervention that resulted in rupture of the right coronary
      artery and pseudoaneurysm formation. Although the pseudoaneurysm regressed over a
      week, it reexpanded after a year. Resection of the pseudoaneurysm and coronary
      artery bypass grafting were performed. The drug-eluting stent at the coronary
      artery injury site may have delayed healing and remodeling of the artery, thus
      contributing to reexpansion of the pseudoaneurysm. 

PMID- 24570570
TI  - Successful endovascular treatment of ruptured bronchial artery aneurysm.
AB  - Rupture of a bronchial artery aneurysm occurs rarely and may mimic aortic
      dissection. A 78-year-old-man was admitted with sudden chest pain. Chest
      radiography showed widening of the mediastinum, suggestive of aortic dissection,
      but contrast-enhanced computed tomography revealed hemomediastinum and bronchial
      artery aneurysm. Although open surgery has been the first choice for ruptured
      bronchial artery aneurysm, this case was successfully treated by an endovascular
      procedure with the combined use of coils and a gelatin sponge. 

PMID- 24570569
TI  - Descending mediastinitis managed by sternotomy, taurolidine and delayed closure.
AB  - Descending necrotizing mediastinitis is a rare complication of upper respiratory
      infections. A quick diagnosis and prompt and complete surgical drainage is
      important for a successful outcome. A 74-year-old man with descending necrotizing
      mediastinitis needed a sternotomy, multiple washouts, and delayed sternal
      closure. 

PMID- 24570571
TI  - Descending necrotizing mediastinitis and sternoclavicular joint osteomyelitis.
AB  - Descending necrotizing mediastinitis is usually associated with cervical or
      odontogenic infections. We describe a patient with blunt trauma to the chest 2
      years earlier, and a slowly developing chest wall hematoma 18 months prior to
      admission, complicated by chronic sternoclavicular joint osteomyelitis,
      eventually leading to descending mediastinitis. Thoracotomy with drainage of the
      mediastinal spaces and multiple procedures for the sternoclavicular joint
      infection were successful. The rarity of this association and undefined optimal
      management prompted this report. 

PMID- 24570572
TI  - Cardiac tamponade due to purulent pericarditis.

PMID- 24570573
TI  - Compressive pneumopericardium following left ventricular-assist device removal.

PMID- 24570574
TI  - Intracardiac metastasis of primary synovial sarcoma of the lung.

PMID- 24570575
TI  - Pericardial constriction due to severely calcified pericardium.

PMID- 24570576
TI  - Huge solitary fibrous tumor of the pleura in a young man.

PMID- 24570578
TI  - Rejoinder to : Who Assumes the Burden of Proof When There's No Neutral Null
      Hypothesis?

PMID- 24570577
TI  - Graft anastomosis technique in the fragile aorta.
AB  - Here, we describe a technique for creating a secure anastomosis between a graft
      and the stump of the aorta, involving the fragile aortic wall between the folded
      flap of the graft inside the aorta and a Teflon felt strip outside. 

PMID- 24570579
TI  - Adaptive Elastic Net for Generalized Methods of Moments.
AB  - Model selection and estimation are crucial parts of econometrics. This paper
      introduces a new technique that can simultaneously estimate and select the model
      in generalized method of moments (GMM) context. The GMM is particularly powerful
      for analyzing complex data sets such as longitudinal and panel data, and it has
      wide applications in econometrics. This paper extends the least squares based
      adaptive elastic net estimator of Zou and Zhang (2009) to nonlinear equation
      systems with endogenous variables. The extension is not trivial and involves a
      new proof technique due to estimators lack of closed form solutions. Compared to
      Bridge-GMM of Caner (2009), we allow for the number of parameters to diverge to
      infinity as well as collinearity among a large number of variables, also the
      redundant parameters set to zero via a data dependent technique. This method has
      the oracle property, meaning that we can estimate nonzero parameters with their
      standard limit and the redundant parameters are dropped from the equations
      simultaneously. Numerical examples are used to illustrate the performance of the
      new method.

PMID- 24570580
TI  - Health Inequalities through the Lens of Health Capital Theory: Issues, Solutions,
      and Future Directions.
AB  - We explore what health-capital theory has to offer in terms of informing and
      directing research into health inequality. We argue that economic theory can help
      in identifying mechanisms through which specific socioeconomic indicators and
      health interact. Our reading of the literature, and our own work, leads us to
      conclude that non-degenerate versions of the Grossman model (1972a;b) and its
      extensions can explain many salient stylized facts on health inequalities. Yet,
      further development is required in at least two directions. First, a childhood
      phase needs to be incorporated, in recognition of the importance of childhood
      endowments and investments in the determination of later-life socioeconomic and
      health outcomes. Second, a unified theory of joint investment in skill (or human)
      capital and in health capital could provide a basis for a theory of the
      relationship between education and health.

PMID- 24570581
TI  - Self-adjustable glasses in the developing world.
AB  - Uncorrected refractive errors are the single largest cause of visual impairment
      globally. Refractive errors are an avoidable cause of visual impairment that are
      easily correctable. Provision of spectacles is a cost-effective measure.
      Unfortunately, this simple solution becomes a public health challenge in low- and
      middle-income countries because of the paucity of human resources for refraction
      and optical services, lack of access to refraction services in rural areas, and
      the cost of spectacles. Low-cost approaches to provide affordable glasses in
      developing countries are critical. A number of approaches has been tried to
      surmount the challenge, including ready-made spectacles, the use of focometers
      and self-adjustable glasses, among other modalities. Recently, self-adjustable
      spectacles have been validated in studies in both children and adults in
      developed and developing countries. A high degree of agreement between self
      adjustable spectacles and cycloplegic subjective refraction has been reported.
      Self-refraction has also been found to be less prone to accommodative inaccuracy
      compared with non-cycloplegic autorefraction. The benefits of self-adjusted
      spectacles include: the potential for correction of both distance and near
      vision, applicability for all ages, the empowerment of lay workers, the increased
      participation of clients, augmented awareness of the mechanism of refraction,
      reduced costs of optical and refraction units in low-resource settings, and a
      relative reduction in costs for refraction services. Concerns requiring attention
      include a need for the improved cosmetic appearance of the currently available
      self-adjustable spectacles, an increased range of correction (currently -6 to +6
      diopters), compliance with international standards, quality and affordability,
      and the likely impact on health systems. Self-adjustable spectacles show poor
      agreement with conventional refraction methods for high myopia and are unable to
      correct astigmatism. A limitation of the fluid-filled adjustable spectacles
      (AdSpecs, Adaptive Eyecare Ltd, Oxford, UK) is that once the spectacles are self
      adjusted and the power fixed, they become unalterable, just like conventional
      spectacles. Therefore, they will need to be changed as refractive power changes
      over time. Current costs of adjustable spectacles are high in developing
      countries and therefore not affordable to a large segment of the population. Self
      adjustable spectacles have potential for "upscaling" if some of the concerns
      raised are addressed satisfactorily. 

PMID- 24570582
TI  - Patient expectations and experiences of multiple sclerosis interferon beta-1a
      treatment: a longitudinal, observational study in routine UK clinical practice.
AB  - BACKGROUND: Premature discontinuation and poor treatment adherence are problems
      in chronic conditions, such as multiple sclerosis in which patients must take
      long-term treatment in order to receive maximum benefit from their medication.
      The Assessing needs In Multiple Sclerosis (AIMS) study explored factors related
      to premature treatment discontinuation and patients' experiences of subcutaneous
      (sc) interferon (IFN) beta-1a treatment in the UK. METHODS: A questionnaire-based
      survey was integrated into the Bupa Home Healthcare patient-support program,
      which delivers sc IFN beta-1a to patients in their home. Data were collected via
      patient questionnaires incorporated into routine clinical care and administered
      upon registration of a new patient by the coordinator, following initial delivery
      of treatment, prior to each delivery during therapy and at the end of treatment.
      Univariate and multivariate analyses were performed to identify factors
      associated with premature discontinuation. RESULTS: Data were collected from
      2,390 patients (1,267 new; 1,123 existing) from 59 UK prescribing centers
      (November 2006-April 2011). Following the first delivery of sc IFN beta-1a, 94%
      (1,149/1,225) of patients had received training, and 73% (818/1,120) reported
      that they had no concerns. In total, 24% of new patients discontinued therapy by
      the end of the study. In the univariate model, none of the candidate variables
      tested were significant predictors of treatment discontinuation. The strongest
      predictors of discontinuation in multivariate analyses were lack of information
      prior to starting treatment and patients feeling unwell on treatment and
      geographic region (P<0.05 for each variable). CONCLUSION: This study suggests
      that patients feeling well on treatment and provision of high-quality information
      are the main determinants of persistence with sc IFN beta-1a therapy. A package
      of care that targets these issues should therefore be considered when initiating
      sc IFN beta-1a therapy.

PMID- 24570583
TI  - Enrichment of breast cancer stem-like cells by growth on electrospun
      polycaprolactone-chitosan nanofiber scaffolds.
AB  - A small population of highly tumorigenic breast cancer cells has recently been
      identified. These cells, known as breast-cancer stem-like cells (BCSC), express
      markers similar to mammary stem cells, and are highly resistant to chemotherapy.
      Currently, study of BCSC is hampered by the inability to propagate these cells in
      tissue culture without inducing differentiation. Recently, it was reported that
      proliferation and differentiation can be modified by culturing cells on
      electrospun nanofibers. Here, we sought to characterize the chemoresistance and
      stem-like properties of breast cancer cell lines grown on nanofiber scaffolds.
      Cells cultured on three-dimensional templates of electrospun poly(epsilon
      caprolactone)-chitosan nanofibers showed increases in mammary stem cell markers
      and in sphere-forming ability compared with cells cultured on polystyrene culture
      dishes. There was no increase in proliferation of stem cell populations,
      indicating that culture on nanofibers may inhibit differentiation of BCSC. The
      increase in stemness was accompanied by increases in resistance to docetaxel and
      doxorubicin. These data indicate that BCSC populations are enriched in cells
      cultured on electrospun poly(epsilon-caprolactone)-chitosan nanofibers, scaffolds
      that may provide a useful system to study BCSC and their response to anticancer
      drug treatment. 

PMID- 24570584
TI  - Risk factors associated with postpartum depression in the Saudi population.
AB  - INTRODUCTION: Postpartum depression (PPD) is one of the major psychological
      disorders worldwide that affects both mother and child. The aim of this study was
      to correlate the risk of PPD with obstetric and demographic variables in Saudi
      females. MATERIALS AND METHODS: Data were collected by interviewing females 8-12
      weeks postpartum. PPD symptoms were defined as present when subjects had an
      Edinburgh Postnatal Depression Scale score of 10 or higher. Variables included in
      this study were age, education, occupation, parity, baby's sex, pregnancy period,
      delivery type, hemoglobin level, anemia, and iron pills taken during pregnancy.
      RESULTS: Of the 352 postpartum females, the prevalence of PPD symptom risk was
      117 (33.2%). Among the PPD symptomatic females, 66 (39.8%) had low hemoglobin
      levels, and 45 (40.5%) females were anemic during pregnancy (P<=0.05). These
      results suggest that early postpartum anemia, indicated by low hemoglobin level,
      is a significant risk factor for PPD (adjusted odds ratio 1.70, 95% confidence
      interval 1.05-2.74; P=0.03). Other variables, including age, parity, education,
      occupation, and delivery type, were not significantly correlated (P=0.15-0.95),
      but marginally indicative of the risk of depressive symptoms. CONCLUSION: Low
      hemoglobin level and anemia during pregnancy were risk factors for PPD in Saudi
      females. Many other factors may be considered risk factors, such as age,
      occupation, and parity. Anemic women need more attention and to be checked
      regarding their PPD, and treated if necessary.

PMID- 24570586
TI  - Olanzapine use in a manic patient during second and third trimester pregnancy.
AB  - Women with bipolar disorder have a high risk for symptom exacerbation during
      pregnancy and the risk is elevated further when mood stabilizers are
      discontinued. This report describes a 31-year-old bipolar woman who discontinued
      medication before pregnancy but had to resume her pharmacotherapy due to manic
      episodes that recurred during the second trimester. Olanzapine, an atypical
      antipsychotic, was administered from week 25 of gestation and then replaced with
      quetiapine in week 35 of gestation. Even though a consensus on clinical
      interventions for pregnant patients with symptom relapse has not been reached,
      clinicians should still discuss pregnancy and therapeutic management with every
      female bipolar patient of childbearing age. This discussion is important because
      treatment can be managed most effectively in these individuals if pregnancy is
      planned. Ultimately, clinical decisions should be made on a case-by-case basis,
      weighing the risks to the mother and fetus between the disorder itself and the
      teratogenicity of pharmacotherapy. 

PMID- 24570585
TI  - Altered baseline brain activity in children with bipolar disorder during mania
      state: a resting-state study.
AB  - BACKGROUND: Previous functional magnetic resonance imaging (fMRI) studies have
      shown abnormal functional connectivity in regions involved in emotion processing
      and regulation in pediatric bipolar disorder (PBD). Recent studies indicate,
      however, that task-dependent neural changes only represent a small fraction of
      the brain's total activity. How the brain allocates the majority of its resources
      at resting state is still unknown. We used the amplitude of low-frequency
      fluctuation (ALFF) method of fMRI to explore the spontaneous neuronal activity in
      resting state in PBD patients. METHODS: Eighteen PBD patients during the mania
      phase and 18 sex-, age- and education-matched healthy subjects were enrolled in
      this study and all patients underwent fMRI scanning. The ALFF method was used to
      compare the resting-state spontaneous neuronal activity between groups.
      Correlation analysis was performed between the ALFF values and Young Mania Rating
      Scale scores. RESULTS: Compared with healthy controls, PBD patients presented
      increased ALFF in bilateral caudate and left pallidum as well as decreased ALFF
      in left precuneus, left superior parietal lobule, and bilateral inferior
      occipital gyrus. Additionally, ALFF values in left pallidum were positively
      correlated with Young Mania Rating Scale score in PBD. CONCLUSION: The abnormal
      resting-state neuronal activities of the basal ganglia, parietal cortex, and
      occipital cortex may play an important role in the pathophysiology in PBD
      patients.

PMID- 24570588
TI  - New generation multi-modal antidepressants: focus on vortioxetine for major
      depressive disorder.
AB  - Vortioxetine is a novel antidepressant with effects on multiple 5-HT receptors
      and on the serotonin transporter. This paper reviews preclinical and clinical
      evidence regarding its mechanism of action, its tolerability, and its efficacy in
      treating major depression. Clinical studies indicate that vortioxetine is
      effective in the treatment of major depression, though there is no suggestion of
      superiority over active comparators. There may be a clinically meaningful
      advantage in terms of tolerability. 

PMID- 24570587
TI  - Psychological morbidity, quality of life, and self-rated health in the military
      personnel.
AB  - OBJECTIVE: The mental health of military personnel varies as a result of
      different cultural, political, and administrative factors. The purpose of this
      study was to evaluate the psychological morbidity and quality of life of military
      personnel in Taiwan. MATERIALS AND METHODS: This cross-sectional study utilized
      the World Health Organization Quality of Life Instrument, brief version, Taiwan
      version, the General Health Questionnaire-12, Chinese version, and the Visual
      Analog Scale (VAS) in several military units. RESULTS: More than half of the
      subjects (55.3%) identified themselves as mentally unhealthy on the General
      Health Questionnaire-12, Chinese version; however, a higher percentage of
      officers perceived themselves as healthy (57.4%) than did noncommissioned
      officers (38.5%) or enlisted men (42.2%). Officers also had higher total quality
      of life (QOL) scores (83.98) than did enlisted men (79.67). Scores on the VAS
      also varied: officers: 72.5; noncommissioned officers: 67.7; and enlisted men:
      66.3. The VAS and QOL were positively correlated with perceived mental health
      among these military personnel. CONCLUSION: Our subjects had higher rates of
      perceiving themselves as mentally unhealthy compared to the general population.
      Those of higher rank perceived themselves as having better mental health and QOL.
      Improving mental health could result in a better QOL in the military. The VAS may
      be a useful tool for the rapid screening of self-reported mental health, which
      may be suitable in cases of stressful missions, such as in disaster rescue;
      however, more studies are needed to determine the optimal cut-off point of this
      measurement tool.

PMID- 24570590
TI  - Ipilimumab in the treatment of metastatic melanoma: management of adverse events.
AB  - Recently, "ipilimumab," an anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4)
      monoclonal antibody, has been demonstrated to improve overall survival in
      metastatic melanoma. "CTLA-4" is an immune-checkpoint molecule that downregulates
      pathways of T-cell activation. Ipilimumab, by targeting CTLA-4, is able to remove
      the CTLA-4 inhibitory signal, allowing the immune system to react to cancer
      cells. Due to its immune-based mechanism of action, ipilimumab causes the
      inhibition of CTLA-4-mediated immunomodulatory effects, the enhancement of
      antitumor specific immune response mediated by the weakening of self-tolerance
      mechanisms while exacerbating the development of autoimmune diseases and immune
      related adverse events, including dermatitis, hepatitis, enterocolitis,
      hypophysitis, and uveitis. 

PMID- 24570589
TI  - Perioperative hyperglycemia is associated with postoperative neurocognitive
      disorders after cardiac surgery.
AB  - OBJECTIVE: Neurocognitive disorders commonly occur following cardiac surgery.
      However, the underlying etiology of these disorders is not well understood. The
      current study examined the association between perioperative glucose levels and
      other risk factors and the onset of neurocognitive disorders in adult patients
      following coronary artery bypass and/or valvular surgery. METHODS: Adult patients
      who underwent their first cardiac surgery at a large tertiary care medical center
      were identified and those with neurocognitive disorders prior to surgery were
      excluded. Demographic, perioperative, and postoperative neurocognitive outcome
      data were extracted from the Society for Thoracic Surgery database, and from
      electronic medical records, between January 2004 and June 2009. Multiple clinical
      risk factors and measures associated with insulin resistance, such as
      hyperglycemia, were assessed. Multivariable Cox competing risk survival models
      were used to assess hyperglycemia and postoperative neurocognitive disorders at
      follow up, adjusting for other risk factors and confounding variables. RESULTS:
      Of the 855 patients included in the study, 271 (31.7%) had new onset
      neurocognitive disorders at follow-up. Age, sex, New York Heart Failure (NYHF)
      Class, length of postoperative intensive care unit stay, perioperative blood
      product transfusion, and other key factors were identified and assessed as
      potential risk factors (or confounders) for neurocognitive disorders at follow
      up. Bivariate analyses suggested that new onset neurocognitive disorders were
      associated with NYHF Class, cardiopulmonary bypass, history of diabetes,
      intraoperative blood product use, and number of diseased coronary vessels, which
      are commonly-accepted risk factors in cardiac surgery. In addition, higher first
      glucose level (median =116 mg/dL) and higher peak glucose >169 mg/dL were
      identified as risk factors. Male sex and nonuse of intra-operative blood products
      appeared to be protective. Controlling for potential risk factors and
      confounders, multivariable Cox survival models suggested that increased
      perioperative first glucose measured in 20 unit increments, was significantly
      associated with the onset of postoperative neurocognitive disorders at follow-up
      (hazard ratio [HR] =1.16, P<0.001) and that women had an elevated risk for this
      outcome (HR =4.18, P=0.01). CONCLUSION: Our study suggests that perioperative
      hyperglycemia was associated with new onset of postoperative neurocognitive
      disorders in adult patients after cardiac surgery, and that men tended to be
      protected from these outcomes. These findings may suggest a need for the revision
      of clinical protocols for perioperative insulin therapy to prevent long-term
      neurocognitive complications.

PMID- 24570591
TI  - Prognostic significance of the combined expression of neutral endopeptidase and
      dipeptidyl peptidase IV in intrahepatic cholangiocarcinoma patients after surgery
      resection.
AB  - AIM: The aim of this study was to investigate the relationship between the
      expression of neutral endopeptidase (NEP) and dipeptidyl peptidase IV (DPP IV)
      proteins, and the clinical significance of the two proteins in patients with
      intrahepatic cholangiocarcinomas (IHCC). METHODS: Expression patterns and
      subcellular localizations of NEP and DPP IV proteins in 186 primary IHCC and 60
      noncancerous liver tissue specimens were detected by immunohistochemistry.
      RESULTS: Both the expression of NEP and DPP IV proteins in IHCC tissues were
      significantly higher than those in noncancerous liver tissues (both P<0.001). Of
      186 patients with IHCC, 128 (68.82%) highly expressed both NEP and DPP IV
      proteins. In addition, the coexpression of NEP and DPP IV proteins was
      significantly associated with advanced tumor stage (P=0.009), positive lymph node
      metastasis (P=0.016) and distant metastasis (P=0.013), and the presence of
      recurrence (P=0.027). Moreover, Kaplan-Meier analysis showed that IHCC patients
      with high NEP expression, high DPP IV expression, and combined overexpression of
      NEP and DPP IV proteins all had poorer overall survival and early recurrence
      after surgery. Furthermore, Cox analysis suggested that NEP expression, DPP IV
      expression, and combined expression of NEP and DPP IV proteins were all
      independent prognostic markers for overall survival and recurrence-free survival
      in patients with IHCC. CONCLUSION: Our data suggest, for the first time, that
      both the expression of NEP and DPP IV proteins may be upregulated in human IHCC
      tissues and the combined expression of NEP and DPP IV proteins may play important
      roles in progression and prognosis of patients with IHCC.

PMID- 24570592
TI  - Synergism from the combination of ulinastatin and curcumin offers greater
      inhibition against colorectal cancer liver metastases via modulating matrix
      metalloproteinase-9 and E-cadherin expression.
AB  - Liver metastasis is a major cause of mortality in colorectal cancer (CRC). The
      current study was to investigate the ability of ulinastatin (UTI) and curcumin
      (CUR) to inhibit CRC liver metastases via modulating matrix metalloproteinase-9
      (MMP-9) and E-cadherin expression. Human CRC HCT-116 cells were treated with
      compounds individually and in combination in order to understand the effect on
      cell migration and invasion. The HCT-116 cell line was established to stably
      express luciferase and green fluorescent protein (GFP) by lentiviral transduction
      (HCT-116-Luc-GFP). We identified an anti-metastasis effect of UTI and CUR on a
      CRC liver metastasis mouse model. Tumor development and therapeutic responses
      were dynamically tracked by bioluminescence imaging. Expression of MMP-9 and E
      cadherin in metastatic tumors was detected by immunohistochemical assay. Results
      of wound healing and cell invasion assays suggest that treatment with UTI, CUR,
      and UTI plus CUR, respectively, significantly inhibit HCT-116 cell migration and
      invasion. Furthermore, results of CRC hepatic metastasis on a nude mouse model
      showed that treatment with UTI, CUR alone, and a combination notably inhibited
      hepatic metastases from CRC and prolonged survival of tumor-bearing mice,
      especially in the UTI plus CUR group. These results suggest that the combination
      of UTI and CUR together may offer greater inhibition against metastasis of CRC. 

PMID- 24570594
TI  - miR-7 inhibits colorectal cancer cell proliferation and induces apoptosis by
      targeting XRCC2.
AB  - BACKGROUND: Analysis using publicly available algorithms predicts that X-ray
      repair complementing defective repair in Chinese hamster cells 2 (XRCC2), a key
      component in the homologous recombination repair pathway, is a potential target
      of micro-ribonucleic acid-7 (miR-7). Some studies have shown that both miR-7 and
      XRCC2 are associated with cancer development. For this purpose, we searched for
      the possible relationship between miR-7 and XRCC2 in the development of
      colorectal cancer (CRC). METHODS: miR-7 expression was assessed in CRC specimens
      and cell lines using real-time polymerase chain reaction (PCR). Luciferase
      reporter assay was used to confirm the target associations. The effect of miR-7
      on cell proliferation and apoptosis was confirmed in vitro by the methylthiazol
      tetrazolium (MTT) assay, colony formation assay, and flow cytometry. Gene and
      protein expression were examined using real time PCR and western blotting,
      respectively. RESULTS: miR-7 was downregulated in CRC specimens and cell lines,
      and targeted the 3' untranslated region of XRCC2. miR-7 overexpression reduced
      cyclin D1 expression and increased p21, caspase-3, and BAX expression, which
      subsequently inhibited CRC cell proliferation and induced CRC cell apoptosis.
      However, XRCC2 can repress the inhibitory effects of miR-7 on proliferation.
      CONCLUSION: Our findings suggest that miR-7 plays a protective role by inhibiting
      proliferation and increasing apoptosis of CRC cells. It may identify new targets
      for anti-cancer treatment.

PMID- 24570593
TI  - Recent advances in the ARID family: focusing on roles in human cancer.
AB  - The human AT-rich interaction domain (ARID) family contains seven subfamilies and
      15 members characterized by having an ARID. Members of the ARID family have the
      ability to regulate transcription and are involved in cell differentiation and
      proliferation. Accumulating evidence suggests that ARID family members are
      involved in cancer-related signaling pathways, highly mutated or differentially
      expressed in tumor tissues, and act as predictive factors for cancer prognosis or
      therapeutic outcome. Here we review the molecular biology and clinical studies
      concerned with the role played by the ARID family in cancer. This may contribute
      to our understanding of the initiation and progression of cancer from a novel
      point of view, as well as providing potential targets for cancer therapy. 

PMID- 24570596
TI  - Higher diastolic blood pressure at admission and antiedema therapy is associated
      with acute kidney injury in acute ischemic stroke patients.
AB  - Antiedema therapy with mannitol and furosemide is widely used for prevention and
      management of cerebral edema, elevated intracranial pressure, and cerebral
      hernia. There are some reports about mannitol and furosemide as risk factors of
      acute kidney injury (AKI). We investigated the risk factors for AKI including
      antiedema therapy in acute ischemic stroke patients. The subjects were 129
      patients with acute ischemic stroke including 56 females and 73 males with a mean
      age 68.16+/-12.29 years. Patients were divided into two groups: patients with AKI
      and without AKI according to Acute Kidney Injury Network criteria. All patients
      had undergone cranial, carotid, and vertebral artery evaluation with magnetic
      resonance imaging. The number of patients with AKI was 14 (10.9%). Subjects
      experiencing atrial fibrillation (P=0.043) and higher diastolic blood pressure
      (DBP) (P=0.032) treated with mannitol (P=0.019) and furosemide (P=0.019)
      disclosed significant association with AKI. Regression analysis revealed that
      higher DBP (P=0.029) and management with mannitol (P=0.044) were the risk factors
      for AKI. Higher DBP at admission is the most important risk factor for AKI.
      However antiedema therapy should be used carefully in patients with acute
      ischemic stroke. Serum creatinine levels or estimated glomerular filtration rate
      should be watched frequently to prevent AKI. 

PMID- 24570595
TI  - Long-term catheterization: current approaches in the diagnosis and treatment of
      port-related infections.
AB  - Since the first description in 1982, totally implanted venous access ports have
      progressively improved patients' quality of life and medical assistance when a
      medical condition requires the use of long-term venous access. Currently, they
      are part of the standard medical care for oncohematologic patients. However,
      apart from mechanical and thrombotic complications, there are also complications
      associated with biofilm development inside the catheters. These biofilms increase
      the cost of medical assistance and extend hospitalization. The most frequently
      involved micro-organisms in these infections are gram-positive cocci. Many
      efforts have been made to understand biofilm formation within the lumen
      catheters, and to resolve catheter-related infection once it has been
      established. Apart from systemic antibiotic treatment, the use of local catheter
      treatment (ie, antibiotic lock technique) is widely employed. Many different
      antimicrobial options have been tested, with different outcomes, in clinical and
      in in vitro assays. The stability of antibiotic concentration in the lock
      solution once instilled inside the catheter lumen remains unresolved. To prevent
      infection, it is mandatory to perform hand hygiene before catheter insertion and
      manipulation, and to disinfect catheter hubs, connectors, and injection ports
      before accessing the catheter. At present, there are still unresolved questions
      regarding the best antimicrobial agent for catheter-related bloodstream infection
      treatment and the duration of concentration stability of the antibiotic solution
      within the lumen of the port. 

PMID- 24570598
TI  - Cutting a mediolateral episiotomy at the correct angle: evaluation of a new
      device, the Episcissors-60.
AB  - BACKGROUND: Anal incontinence is nine times more prevalent in women than in men
      due to obstetric anal sphincter injury (OASI). OASI is linked to midline
      episiotomies and mediolateral episiotomies with post-delivery angles of <30 and
      >60 degrees. Studies show that doctors and midwives are unable to correctly
      "eyeball" the safe angle required due to perineal stretching by the fetal head at
      crowning. A new scissor instrument (Episcissors-60) was devised to allow cutting
      a mediolateral episiotomy at a fixed angle of 60 degrees from the perineal
      midline. METHODS: Scissors with a marker guide limb pointing towards the anus
      were devised, ensuring an angle of 60 degrees between the scissor blades and the
      guide limb. This device was initially tested in models. Post-delivery angles were
      recorded on transparencies and analyzed by an author blinded to clinical details.
      Accoucheurs were asked to rate the ease of use on a 5-point scale. RESULTS: Of
      the 17 women, 14 delivered with ventouse, two with forceps, and one with
      sequential ventouse-forceps. Indications for instrumental delivery were
      suboptimal cardiotocogram and/or prolonged second stage of labor. Mean birth
      weight was 3.41 (2.92-4.12) kg. A mean post-delivery angle of 42.4+/-7 (range 30
      60, median 43) degrees (95% confidence interval 38.8-46) was achieved with the
      Episcissors-60 instrument. Eighty-eight percent of clinicians agreed or strongly
      agreed that the scissors were easy to use. CONCLUSION: The Episcissors-60
      delivered a consistent post-delivery angle of 43 degrees. They could replace
      "eyeballing" when performing mediolateral episiotomies and form part of a
      preventative strategy to reduce OASI.

PMID- 24570597
TI  - New and emerging contraceptives: a state-of-the-art review.
AB  - BACKGROUND: The first hormonal contraceptive was introduced onto the market in
      several countries 50 years ago; however, the portfolio of contraceptive methods
      remains restricted with regards to their steroid composition, their cost, and
      their ability to satisfy the requirements of millions of women/couples in
      accordance with their different reproductive intentions, behaviors, cultures, and
      settings. METHODS: A literature review was conducted using Medline, Embase, and
      Current Contents databases, up to September 1, 2013 to identify publications
      reporting new contraceptives in development using combinations of the search
      terms: contraception, contraceptives, oral contraceptives, patch, vaginal ring,
      implants, intrauterine contraceptives, and emergency contraception (EC). Also,
      several experts in the field were also consulted to document ongoing projects on
      contraception development. Additionally, the Clinicaltrial.gov website was
      searched for ongoing studies on existing contraceptive methods and new and
      emerging female contraceptives developed over the past 5 years. Information was
      also obtained from the pharmaceutical industry. RESULTS: Early sexual debut and
      late menopause means that women may require contraception for up to 30 years.
      Although oral, injectable, vaginal, transdermal, subdermal, and intrauterine
      contraceptives are already available, new contraceptives have been developed in
      an attempt to reduce side effects and avoid early discontinuation, and to fulfill
      women's different requirements. Research efforts are focused on replacing ethinyl
      estradiol with natural estradiol to reduce thrombotic events. In addition, new,
      less androgenic progestins are being introduced and selective progesterone
      receptor modulators and new delivery systems are being used. In addition,
      research is being conducted into methods that offer dual protection
      (contraception and protection against human immunodeficiency virus transmission),
      and contraceptives for use "on demand." Studies are also investigating non
      hormonal contraceptive methods that have additional, non-contraceptive benefits.
      CONCLUSION: The most pressing need worldwide is, first, that the highly effective
      contraceptive methods already available should be affordable to most of the
      population and also that these methods should fulfill the needs of women of
      different ages and with different reproductive requirements. The development of
      new contraceptive methods should also take advantage of the knowledge obtained
      over the past 30 years on gamete physiology and gamete interaction to avoid the
      use of steroid compounds.

PMID- 24570599
TI  - Criterion-Related Validity of Sit-and-Reach Tests for Estimating Hamstring and
      Lumbar Extensibility: a Meta-Analysis.
AB  - The main purpose of the present meta-analysis was to examine the scientific
      literature on the criterion-related validity of sit-and-reach tests for
      estimating hamstring and lumbar extensibility. For this purpose relevant studies
      were searched from seven electronic databases dated up through December 2012.
      Primary outcomes of criterion-related validity were Pearson's zero-order
      correlation coefficients (r) between sit-and-reach tests and hamstrings and/or
      lumbar extensibility criterion measures. Then, from the included studies, the
      Hunter- Schmidt's psychometric meta-analysis approach was conducted to estimate
      population criterion- related validity of sit-and-reach tests. Firstly, the
      corrected correlation mean (rp), unaffected by statistical artefacts (i.e.,
      sampling error and measurement error), was calculated separately for each sit-and
      reach test. Subsequently, the three potential moderator variables (sex of
      participants, age of participants, and level of hamstring extensibility) were
      examined by a partially hierarchical analysis. Of the 34 studies included in the
      present meta-analysis, 99 correlations values across eight sit-and-reach tests
      and 51 across seven sit-and-reach tests were retrieved for hamstring and lumbar
      extensibility, respectively. The overall results showed that all sit-and-reach
      tests had a moderate mean criterion-related validity for estimating hamstring
      extensibility (rp = 0.46-0.67), but they had a low mean for estimating lumbar
      extensibility (rp = 0. 16-0.35). Generally, females, adults and participants with
      high levels of hamstring extensibility tended to have greater mean values of
      criterion-related validity for estimating hamstring extensibility. When the use
      of angular tests is limited such as in a school setting or in large scale
      studies, scientists and practitioners could use the sit-and-reach tests as a
      useful alternative for hamstring extensibility estimation, but not for estimating
      lumbar extensibility. Key PointsOverall sit-and-reach tests have a moderate mean
      criterion-related validity for estimating hamstring extensibility, but they have
      a low mean validity for estimating lumbar extensibility.Among all the sit-and
      reach test protocols, the Classic sit-and-reach test seems to be the best option
      to estimate hamstring extensibility.End scores (e.g., the Classic sit-and-reach
      test) are a better indicator of hamstring extensibility than the modifications
      that incorporate fingers-to-box distance (e.g., the Modified sit-and-reach
      test).When angular tests such as straight leg raise or knee extension tests
      cannot be used, sit-and-reach tests seem to be a useful field test alternative to
      estimate hamstring extensibility, but not to estimate lumbar extensibility. 

PMID- 24570600
TI  - VEGF and BFGF Expression and Histological Characteristics of the Bone-Tendon
      Junction during Acute Injury Healing.
AB  - Bone-tendon junction (BTJ) injuries are common and may be caused by acute trauma
      and delayed healing during exercise or work. To understand the nature of the
      healing process of BTJ injuries would help to prevent injuries and improve
      treatment. Thirty-three mature female rabbit hindlimbs were assigned to normal
      control (CON, n = 7) and injury groups (n = 26). The acute injury was established
      by administering one 7 plum-blossom needle puncture. Specimens were harvested
      post injury at 1, 2, 4, and 8 weeks (ND1W, n = 6; ND2W, n = 6; ND4W, n = 7; and
      ND8W, n = 7). The injury existed in all of the injury groups. Compared with the
      CON group, all of the animals in the injury group showed poor cell profiles, an
      unclear or undetectable tide mark, a proteoglycan area and profile changes; the
      BTJ cell density diminished significantly in the ND1W (p < 0.01), ND2W (p <
      0.05), ND4W (p < 0.01), and ND8W groups (p < 0.01); the fibrocartilage zone
      thickness in all injury groups was significantly thicker than in the CON group (p
      < 0.05), but no significant difference was found among the injury groups
      (p>0.05). The basic fibroblast growth factor (bFGF) expression in the CON group
      was significantly less than in the ND1W group (p<0.01), but no significant
      difference was found when compared with the ND2W, ND4W, and ND8W groups. The bFGF
      expression in the ND1W group was higher than that of the ND4W (p < 0.05) and ND8W
      groups (p < 0.01). The vascular endothelial growth factor (VEGF) levels were not
      significantly different among the groups (p > 0.05). The bFGF and VEGF expression
      levels indicated that the healing process stopped at 8 weeks post injury or was
      not activated, although the injury had not healed by histological examination. A
      repeatable animal model of BTJ acute injury was established in this study, and
      the results described the BTJ acute injury healing difficult concerned with the
      repairing stop. Key PointsThis study described the bone-tendon junction acute
      injury nature healing process.The bone-tendon junction acute injury could not be
      repaired naturally in 8 weeks.The bFGF and VEGF expression revealed that the bone
      tendon junction acute injury delayed healing concern with the repairing stop. 

PMID- 24570601
TI  - Evidence of a Non-Linear Dose-Response Relationship between Training Load and
      Stress Markers in Elite Female Futsal Players.
AB  - THE AIM OF THIS STUDY WAS: to describe typical training load (TL) carried out by
      a professional female futsal team for a period of 5 weeks; and to verify the
      relationship between TL, stress symptoms, salivary secretory immunoglobulin A
      (SIgA) levels, and symptoms of upper respiratory infections (URI). Over 45
      sessions, the TL of the athletes was monitored daily by means of session-RPE
      method during the in-season period prior to the main national competition. Stress
      symptoms were measured weekly by means of the "Daily Analysis of Life Demands in
      Athletes Questionnaire" (DALDA), SIgA levels, and by symptoms of URI by the
      "Wisconsin Upper Respiratory Symptom Survey-21" (WURSS). There was a significant
      increase in TL, monotony, and training strain in week 3, with a concomitant and
      significant reduction in percentage variation (Delta%) of SIgA concentration and
      secretion rate (p < 0.05). Additionally, a second order regression model showed a
      high goodness of fit (R(2) = 0.64 - 0.89) between TL and strain with SIgA
      concentration, secretion rate, and "worse than normal" responses of stress
      symptoms from the questionnaire. In conclusion, a link between TL and SIgA
      levels, and stress symptoms in female futsal players was evident in a non linear
      fashion. There appears to be an optimal range of values of daily TL between ~343
      and ~419 AU and strain between ~2639 and 3060 AU, because at levels below and
      above these values there was an increase in stress symptoms and above ~435 and
      ~3160 AU to TL and strain there were a decrease in SIgA levels. In contrast,
      symptoms of URI failed to demonstrate relationship with the variables studied.
      Key PointsThere is a dose-response relationship between SIgA levels and stress
      symptoms with TL.For the athletes of the present study, values of ~436 AU and
      ~3161 AU to TL and strain training would be desirable because higher values would
      decrease responses of SIgA levels.An optimal range of values of TL between ~336
      and ~412 AU to TL and ~2610 and ~3016 AU to strain training would be suggested
      for this group of athletes, since below and above these values increased
      responses of stress symptoms were observed.

PMID- 24570602
TI  - Acute Whole-Body Vibration does not Facilitate Peak Torque and Stretch Reflex in
      Healthy Adults.
AB  - The acute effect of whole-body vibration (WBV) training may enhance muscular
      performance via neural potentiation of the stretch reflex. The purpose of this
      study was to investigate if acute WBV exposure affects the stretch induced knee
      jerk reflex [onset latency and electromechanical delay (EMD)] and the isokinetic
      knee extensor peak torque performance. Twenty-two subjects were randomly assigned
      to the intervention or control group. The intervention group received WBV in a
      semi-squat position at 30 degrees  knee flexion with an amplitude of 0.69 mm,
      frequency of 45 Hz, and peak acceleration of 27.6 m/s(2) for 3 minutes. The
      control group underwent the same semii-squatting position statically without
      exposure of WBV. Two-way mixed repeated measures analysis of variance revealed no
      significant group effects differences on reflex latency of rectus femoris (RF)
      and vastus lateralis (VL; p = 0.934 and 0.935, respectively) EMD of RF and VL (p
      = 0.474 and 0.551, respectively) and peak torque production (p = 0.483) measured
      before and after the WBV. The results of this study indicate that a single
      session of WBV exposure has no potentiation effect on the stretch induced reflex
      and peak torque performance in healthy young adults. Key PointsThere is no acute
      potentiation of stretch reflex right after whole body vibration.Acute whole body
      vibration does not improve mus-cle peak torque performance in healthy young
      adults. 

PMID- 24570603
TI  - The effect of additional dead space on respiratory exchange ratio and carbon
      dioxide production due to training.
AB  - The purpose of the study was to investigate the effects of implementing
      additional respiratory dead space during cycloergometry-based aerobic training.
      The primary outcome measures were respiratory exchange ratio (RER) and carbon
      dioxide production (VCO2). Two groups of young healthy males: Experimental (Exp,
      n = 15) and Control (Con, n = 15), participated in this study. The training
      consisted of 12 sessions, performed twice a week for 6 weeks. A single training
      session consisted of continuous, constant-rate exercise on a cycle ergometer at
      60% of VO2max which was maintained for 30 minutes. Subjects in Exp group were
      breathing through additional respiratory dead space (1200ml), while subjects in
      Con group were breathing without additional dead space. Pre-test and two post
      training incremental exercise tests were performed for the detection of gas
      exchange variables. In all training sessions, pCO2 was higher and blood pH was
      lower in the Exp group (p < 0.001) ensuring respiratory acidosis. A 12-session
      training program resulted in significant increase in performance time in both
      groups (from 17"29 +/- 1"31 to 18"47 +/- 1"37 in Exp; p=0.02 and from 17"20 +/-
      1"18 to 18"45 +/- 1"44 in Con; p = 0.02), but has not revealed a significant
      difference in RER and VCO2 in both post-training tests, performed at rest and
      during submaximal workload. We interpret the lack of difference in post-training
      values of RER and VCO2 between groups as an absence of inhibition in glycolysis
      and glycogenolysis during exercise with additional dead space. Key PointsThe
      purpose of the study was to investigate the effects of implementing additional
      respiratory dead space during cycloergometry-based aerobic training on
      respiratory exchange ratio and carbon dioxide production.In all training
      sessions, respiratory acidosis was gained by experimental group only.No
      significant difference in RER and VCO2 between experimental and control group due
      to the trainings.The lack of difference in post-training values of RER and VCO2
      between groups means absence of inhibition in glycolysis and glycogenolysis
      during exercise with additional dead space. 

PMID- 24570604
TI  - Attitudes and motivations of competitive cyclists regarding use of banned and
      legal performance enhancers.
AB  - Drug 'doping' and the use of banned performance enhancing products (PEPs) remains
      an issue in virtually all competitive sports despite penal consequences and known
      health risks. The lines distinguishing "fair" and "unfair" performance
      enhancement have become increasingly blurred. Few studies have explored how
      attitudes towards legal performance enhancers (drugs/substances, diet, and
      equipment modifications) may influence motivations to use banned PEPs. In the
      present study, 68 competitive cyclists completed a survey examining the
      importance of choosing banned and non-banned PEPs using World Anti-Doping Agency
      (WADA) and Union Cycliste Internationale (UCI) criteria. Results showed that over
      60 percent of cyclists used non-banned PEPs while 8 percent used banned PEPs.
      Health was overall the most important factor in choosing a PEP while apprehension
      by a doping agency was least important. Mixed- model ANOVA analyses revealed that
      motivations to use banned PEPs were complex, as the importance of health,
      violating the sprit of the sport, performance improvement, and getting caught
      were differentially influenced by PEP legality (p < 0.001) and whether a cyclist
      endorsed non-banned PEP use (p < 0.001). The importance of winning, sponsorship,
      and maintaining competitiveness did not influence non-banned PEP use (p > 0.05).
      Our findings illustrate the multifactorial nature of PEP use/doping attitudes and
      highlight the unique role that "legal" performance enhancement may plays in
      influencing banned and/or unethical sports behaviors. Key PointsUse of
      performance enhancers is high even among non-professional athletesCyclists
      overall rated "risk to health" as the most important factor in choosing to use a
      performance enhancing product.Motivations to use banned performance enhancer are
      complex and are significantly influenced by whether an athlete utilizes "legal"
      performance enhancers. 

PMID- 24570605
TI  - Comparing fat oxidation in an exercise test with moderate-intensity interval
      training.
AB  - This study compared fat oxidation rate from a graded exercise test (GXT) with a
      moderate-intensity interval training session (MIIT) in obese men. Twelve
      sedentary obese males (age 29 +/- 4.1 years; BMI 29.1 +/- 2.4 kg.m(-2); fat mass
      31.7 +/- 4.4 %body mass) completed two exercise sessions: GXT to determine
      maximal fat oxidation (MFO) and maximal aerobic power (VO2max), and an interval
      cycling session during which respiratory gases were measured. The 30-min MIIT
      involved 5-min repetitions of workloads 20% below and 20% above the MFO
      intensity. VO2max was 31.8 +/- 5.5 ml.kg(-1).min(-1) and all participants
      achieved >= 3 of the designated VO2max test criteria. The MFO identified during
      the GXT was not significantly different compared with the average fat oxidation
      rate in the MIIT session. During the MIIT session, fat oxidation rate increased
      with time; the highest rate (0.18 +/- 0.11 g.min(- 1)) in minute 25 was
      significantly higher than the rate at minute 5 and 15 (p <= 0.01 and 0.05
      respectively). In this cohort with low aerobic fitness, fat oxidation during the
      MIIT session was comparable with the MFO determined during a GXT. Future research
      may consider if the varying workload in moderate-intensity interval training
      helps adherence to exercise without compromising fat oxidation. Key PointsFat
      oxidation during interval exercise is not com-promised by the undulating exercise
      intensityPhysiological measures corresponding with the MFO measured during the
      GXT correlated well to the MIITThe validity of exercise intensity markers derived
      from a GXT to reflect the physiological responses during MIIT. 

PMID- 24570606
TI  - Does the Timing of Measurement Alter Session-RPE in Boxers?
AB  - The purpose of this study was to compare the influence of measuring the overall
      session rating of perceived exertion (session-RPE) at 10 vs. 30 minutes following
      exercise. Eight boxers completed three different standardized training sessions
      of different intensities (easy, moderate and hard) in a matchedpairs, randomized
      research design. Exercise intensity was assessed during each bout by measuring
      heart rate, blood lactate concentration and session-RPE. To assess the effect of
      measurement timing on session-RPE, RPE data were collected either 10 or 30
      minutes post-exercise. There was no significant effect of measurement time on
      session-RPE values following easy (10 minutes: session-RPE = 1.3 +/- 1.0
      Arbitrary Unit (AU), %Heart Rate Reserve (HRR) = 49.5 +/- 11.1, and ?Blood
      lactate = -2.3 +/- 16.3%; 30 minutes: session-RPE = 1.7 +/- 1.0 AU, %HRR = 51.3
      +/- 10.8, and ?Blood lactate = 0.7 +/- 25.2%), moderate (10 minutes: session-RPE
      = 2.7 +/- 1.6 AU, %HRR = 67.2 +/- 10.8, and ?Blood lactate = 2.2 +/- 19%; 30
      minutes: session-RPE = 2.5 +/- 0.9 AU, %HRR = 67.2 +/- 5.9, and ?Blood lactate =
      24.5 +/- 17.1%) and hard (10 minutes: session-RPE = 5.7 +/- 1.0 AU, %HRR = 88.1
      +/- 6.3, and ?Blood lactate = 146.3 +/- 87.9%; 30 minutes: session-RPE = 5.8 +/-
      1.9 AU, %HRR> = 83.3 +/- 8.0, and ?Blood lactate = 91.6 +/- 39%) sessions. In
      conclusion, our findings suggest that session-RPE can be used in boxing training
      routines across a range of intensities and accurate measurements can be
      determined as early as 10 minutes after exercise. Key PointsIt is difficult to
      quantify and monitoring the external training load in martial arts (e.g. Aikido,
      Kung Fu, Judo) and physical combat sports (e.g. Boxing, Muay Thai), session RPE
      method appears to be a reliable method to quantifying training load in those
      sports.For many athletes it is impractical to wait 30 minutes after training
      session to provide a session-RPE. The present findings show that collecting ses
      sion-RPE measures at 10 min following exercise ses-sions of various intensities
      (i.e. easy, moderate, and hard) provide similar values as if taken 30 min fol
      lowing the session.Our data have significant practical benefit and fur-ther
      support the practical usefulness of session-RPE for measuring internal training
      load in sport. 

PMID- 24570607
TI  - Effect of uncertainty during the lunge in fencing.
AB  - The aim of this study is to determine the effect that uncertainty, in relation to
      the probability of error, exerts on the reaction response and speed during the
      lunge in fencing. The participants were 18 regional-level fencers with over five
      years' experience. Force platforms under the feet recorded the horizontal
      components of the reaction forces, from which the kinematic parameters of the
      center of mass were calculated. An electronic system to present stimuli,
      controlled by a programmable clock, projected a target onto a screen that
      represented a plastron. In situations without uncertainty, the fencers had to
      lunge as swiftly as possible when a circle (the target) appeared in the center of
      the plastron, trying to touch the center of the circle with the tip of the sword.
      In situations with uncertainty, the fencers had the same target as in the
      previous situation but they received the information that they had to change the
      lunge into a defensive move if the target disappeared from the plastron during
      the action. The results indicate that the reaction time and the movement time
      increased with uncertainty. Although there were no differences for the horizontal
      velocity of the center of mass at the end of the acceleration phase, the mean
      horizontal velocity of the lunge was reduced by the effect of the uncertainty.
      Prior knowledge of the opponent's possible action implies a reduction in
      uncertainty, reducing movement time as well as meaning faster execution, thereby
      increasing the success of the lunge in fencing. Key PointsReaction time (RT) and
      the movement time (MT) increase when doubts arise about being able to reach the
      target as planned during the lunge.The horizontal velocity of the lunge decreases
      by the effect of uncertainty due to the possibility that the events might not
      occur as planned.These results highlight the importance that tactical intent has
      in fencing for successfully predicting the defensive movements of the opponent
      during the attack. 

PMID- 24570608
TI  - Lactate Kinetics during Multiple Set Resistance Exercise.
AB  - Intensive exercise like strength training increases blood lactate concentration
      [La]. [La] is commonly used to define the metabolic stress of an exercise and
      depends on the lactate production, transportation, metabolism, and elimination.
      This investigation compared multiple set training of different volumes to show
      the influence of exercise volume on [La]. Ten male subjects performed 3 sets of
      resistance exercises within 4 separate sessions: Arm Curl with 1 or 2 arms (AC1
      or AC2), and Leg Extension with 1 or 2 legs (LE1 or LE2). Each set was performed
      at a standard velocity and at a previously determined 10RM load. Blood lactate
      samples were taken immediately before and after each set (pre1, post1, pre2,
      post2, pre3, post3). Maximum [La] was significantly higher after LE2 (6.8 +/-
      1.6mmol.L(-1)) and significantly lower after AC1 (2.8 +/- 0.7mmol.L(-1)) in
      comparison with the other exercise protocols. There was no difference between AC2
      (4.3 +/- 1.1mmol.L(-1)) and LE1 (4.4 +/- 1.1mmol.L(-1)). Surprisingly, [La]
      decreased during the 3(rd) set (for AC exercise), and during both the 2(nd) and
      3(rd) sets (for LE exercise) and increased only during the recovery phases. In
      contrast to our expectations, blood [La] decreased during the 2(nd) and 3(rd)
      exercise sets and further increased only during recovery phases. However, from
      the increases observed following the first set, we know that lactate was produced
      and transported to the blood during our exercise protocol. We speculate that
      lactate is taken up and metabolized by distal muscle fibres or organs. In
      addition, as the decreases occurred within a short period of time, blood volume
      shifts and/or the muscle-to-blood gradient may account for the rapid decreases in
      [La]. Key PointsBlood lactate concentration [La] decreases during the 2(nd) and
      3(rd) set of a resistance exercise program of the leg extensor muscles.[La]
      decreases during the 3(rd) set of a resistance exercise program of the arm flexor
      muscles.A significant increase of [La] only appears during the first set, during
      rest periods and after the last set.The decline of [La] during sets becomes
      larger over the course of exercise. 

PMID- 24570609
TI  - A comparison of jump height, takeoff velocities, and blocking coverage in the
      swing and traditional volleyball blocking techniques.
AB  - The purpose of this study was to compare traditional and swing blocking
      techniques on center of mass (COM) projectile motion and effective blocking area
      in nine healthy Division I female volleyball players. Two high-definition (1080
      p) video cameras (60 Hz) were used to collect two-dimensional variables from two
      separate views. One was placed perpendicular to the plane of the net and the
      other was directed along the top of the net, and were used to estimate COM
      locations and blocking area in a plane parallel to the net and hand penetration
      through the plane of the net respectively. Video of both the traditional and
      swing techniques were digitized and kinematic variables were calculated. Paired
      samples t-tests indicated that the swing technique resulted in greater (p < 0.05)
      vertical and horizontal takeoff velocities (vy and vx), jump height (H), duration
      of the block (tBLOCK), blocking coverage during the block (C) as well as hand
      penetration above and through the net's plane (YPEN, ZPEN). The traditional
      technique had significantly greater approach time (tAPP). The results of this
      study suggest that the swing technique results in both greater jump height and
      effective blocking area. However, the shorter tAPP that occurs with swing is
      associated with longer times in the air during the block which may reduce the
      ability of the athlete to make adjustments to attacks designed to misdirect the
      defense. Key PointsSwing blocking technique has greater jump height, effective
      blocking area, hand penetration, horizontal and vertical takeoff velocity, and
      has a shorter time of approach.Despite these advantages, there may be more
      potential for mistiming blocks and having erratic deflections of the ball after
      contact when using the swing technique.Coaches should take more than simple jump
      height and hand penetration into account when deciding which technique to employ.

PMID- 24570610
TI  - Comparison of the effects of local cryotherapy and passive cross-body stretch on
      extensibility in subjects with posterior shoulder tightness.
AB  - The objective was to compare the immediate effects of local cryotherapy (LC) and
      passive cross-body stretch on the extensibility of the posterior shoulder muscle
      in individuals with posterior shoulder tightness. Eighty-seven healthy subjects
      with a between-shoulder difference in internal rotation (IR) range of motion
      (ROM) greater than 10 degrees  were randomly divided into three groups: LC group,
      stretching group, and control group (n = 29 in each group). Subjects in the LC
      group received LC on infraspinatus and posterior deltoid muscles and subjects in
      the stretching group performed passive cross-body stretch. Stretch sensation was
      measured at the end range of passive IR and horizontal adduction (HA) using
      numerical rating scale, and the pressure pain threshold (PPT) at the
      infraspinatus and posterior deltoid muscles was measured using pressure
      algometry. Passive and active ROM of IR and HA of the glenohumeral joint were
      measured using an inclinometer. All measurements were performed at pre
      intervention, post- intervention, and 10-min follow-up. Stretch sensation was
      significantly decreased and PPT was significantly increased in the LC and
      stretching groups at post-intervention, and these effects were maintained at 10
      min follow-up, compared to the control group. Both the LC group and stretching
      group had a significantly greater increase in passive and active ROM of IR and
      HA, compared to the control group at post-intervention and 10-min follow-up.
      However, there were no significant differences in stretch sensation, PPT, or ROM
      of IR and HA between the LC group and stretching group. LC can be used to
      decrease the stretch sensation and increase PPT and ROM of IR and HA as much as a
      stretching exercise. LC could be an alternative method for increasing the
      restricted ROM of glenohumeral IR and HA for individuals with posterior shoulder
      tightness, especially for patients and sports players who have severe stretching
      discomfort. Key PointsLocal cryotherapy (LC) decreased the uncomfortable stretch
      sensation, and increased the pressure pain threshold (PPT) of infraspinatus and
      posterior deltoid muscles in subjects with posterior shoulder tightness.Decreased
      stretch sensation by LC without passive stretching could improve the passive and
      active ROM of internal rotation and horizontal adduction in subjects with
      posterior shoulder tightness, similar to cross-body stretch.LC can be an
      alternative method to increase extensibility when individuals with posterior
      shoulder tightness have high stretch sensitivity and low PPT in the infraspinatus
      and posterior deltoid muscles. 

PMID- 24570611
TI  - Hormone responses to an acute bout of low intensity blood flow restricted
      resistance exercise in college-aged females.
AB  - The purpose of this study was to determine whether the acute hormone response to
      exercise differed between low intensity blood flow restricted resistance exercise
      and traditional high-intensity resistance exercise in college-aged women. A total
      of 13 healthy women (aged 18-25 yrs), who were taking oral contraceptives,
      volunteered for this randomized crossover study. Subjects performed a session of
      low intensity blood flow restricted resistance exercise (BFR) (20% of 1-RM, 1 set
      30 reps, 2 sets 15 reps) and a session of traditional high intensity resistance
      exercise without blood flow restriction (HI) (3 sets of 10 repetitions at 80% of
      1-RM) on separate days. Fasting serum cortisol and growth hormone (GH) and blood
      lactate responses were measured in the morning pre and post exercise sessions. GH
      (Change: HI: 6.34 +/- 1.72; BFR: 4.22 +/- 1.40 ng.mL(-1)) and cortisol (Change:
      HI: 4.46 +/- 1.53; BFR: 8.10 +/- 2.30 ug.dL(-1)) significantly (p < 0.05)
      increased immediately post exercise for both protocols compared to baseline and
      there were no significant differences between the protocols for these responses.
      In contrast, blood lactate levels (HI: 7.35 +/- 0.45; BFR: 4.02 +/- 0.33 mmol.L(
      1)) and ratings of perceived exertion were significantly (p < 0.01) higher for
      the HI protocol. In conclusion, acute BFR restricted resistance exercise
      stimulated similar increases in anabolic and catabolic hormone responses in young
      women. Key PointsGrowth hormone and cortisol levels significantly increased after
      a single bout of low intensity blood flow restricted resistance exercise in young
      women.There were no significant differences in hormone responses between the low
      intensity blood flow restricted protocol and the traditional high intensity
      higher total workload protocol.Low intensity blood flow restricted resistance
      exercise provides a sufficient stimulus to elicit anabolic and catabolic hormone
      responses in young women. 

PMID- 24570612
TI  - Does a non-circular chainring improve performance in the bicycle motocross
      cycling start sprint?
AB  - Maximising power output during the initial acceleration phase of a bicycle
      motocross (BMX) race increases the chance to lead the group for the rest of the
      race. The purpose of this study was to investigate the effect of non-circular
      chainrings (Q-ring) on performance during the initial acceleration phase of a BMX
      race. Sixteen male cyclists (Spanish National BMX team) performed two
      counterbalanced and randomized initial sprints (3.95s), using Q- ring vs.
      circular chainring, on a BMX track. The sample was divided into two different
      groups according to their performance (Elite; n = 8 vs. Cadet; n = 8). Elite
      group covered a greater distance using Q-ring (+0.26 m, p = 0.02; D = 0.23),
      whilst the improvement for the Cadet (+0.04 m) was not significant (p = 0.87; D =
      -0.02). Also, there was no significant difference in power output for the Elite
      group, while the Cadet group revealed larger peak power with the circular
      chainring. Neither lactate level, nor heart rate showed significant differences
      due to the different chainring used. The non-circular chainring improved the
      initial acceleration capacity only in the Elite riders. Key PointsThis work
      provides novel results demonstrating very significant improvements in the sprint
      performance of BMX cycling discipline using a non-circular chainring system.This
      study seeks a practical application from scientific analysisAll data are obtained
      in a real context of high competition using a sample comprised by the National
      Spanish Team.Some variables influencing performance as subjects' physical fitness
      are discussed.Technical equipment approved by International Cycling Union is
      studied to check its potentially beneficial influence on performance. 

PMID- 24570613
TI  - Effects of baseline levels of flexibility and vertical jump ability on
      performance following different volumes of static stretching and potentiating
      exercises in elite gymnasts.
AB  - This study examined the effects of baseline flexibility and vertical jump ability
      on straight leg raise range of motion (ROM) and counter-movement jump performance
      (CMJ) following different volumes of stretching and potentiating exercises. ROM
      and CMJ were measured after two different warm-up protocols involving static
      stretching and potentiating exercises. Three groups of elite athletes (10 male,
      14 female artistic gymnasts and 10 female rhythmic gymnasts) varying greatly in
      ROM and CMJ, performed two warm-up routines. One warm-up included short (15 s)
      static stretching followed by 5 tuck jumps, while the other included long static
      stretching (30 s) followed by 3x5 tuck jumps. ROM and CMJ were measured before,
      during and for 12 min after the two warm-up routines. Three-way ANOVA showed
      large differences between the three groups in baseline ROM and CMJ performance. A
      type of warm-up x time interaction was found for both ROM (p = 0.031) and CMJ (p
      = 0.016). However, all athletes, irrespective of group, responded in a similar
      fashion to the different warm-up protocols for both ROM and CMJ, as indicated
      from the lack of significant interactions for group (condition x group, time x
      group or condition x time x group). In the short warm-up protocol, ROM was not
      affected by stretching, while in the long warm-up protocol ROM increased by 5.9%
      +/- 0.7% (p = 0.001) after stretching. Similarly, CMJ remained unchanged after
      the short warm-up protocol, but increased by 4.6 +/- 0.9% (p = 0.012) 4 min after
      the long warm- up protocol, despite the increased ROM. It is concluded that the
      initial levels of flexibility and CMJ performance do not alter the responses of
      elite gymnasts to warm-up protocols differing in stretching and potentiating
      exercise volumes. Furthermore, 3 sets of 5 tuck jumps result in a relatively
      large increase in CMJ performance despite an increase in flexibility in these
      highly-trained athletes. Key PointsThe initial levels of flexibility and vertical
      jump ability have no effect on straight leg raise range of motion (ROM) and
      counter-movement jump performance (CMJ) of elite gymnasts following warm-up
      protocols differing in stretching and potentiating exercise volumesStretching of
      the main leg muscle groups for only 15 s has no effect on ROM of elite gymnastsIn
      these highly-trained athletes, one set of 5 tuck jumps during warm-up is not
      adequate to increase CMJ performance, while 3 sets of 5 tuck jumps result in a
      relatively large increase in CMJ performance (by 4.6% above baseline), despite a
      5.9% increase in flexibility due to the 30 s stretching exercises. 

PMID- 24570614
TI  - Effects of cadence on aerobic capacity following a prolonged, varied intensity
      cycling trial.
AB  - We determined if high cadences, during a prolonged cycling protocol with varying
      intensities (similar to race situations) decrease performance compared to cycling
      at a lower, more energetically optimal, cadence. Eight healthy, competitive male
      road cyclists (35 +/- 2 yr) cycled for 180 min at either 80 or 100 rpm
      (randomized) with varying intensities of power outputs corresponding to 50, 65
      and 80% of VO2max. At the end of this cycling period, participants completed a
      ramped exercise test to exhaustion at their preferred cadence (90 +/- 7 rpm).
      There were no cadence differences in blood glucose, respiratory exchange ratio or
      rate of perceived exertion. Heart Rate, VO2 and blood lactate were higher at 100
      rpm vs. 80 rpm. The total energy cost while cycling during the 65% and 80% VO2max
      intervals at 100 rpm (15.2 +/- 2.7 and 19.1 +/- 2.5 kcal?min(-1), respectively)
      were higher than at 80 rpm (14.3 +/- 2.7 and 18.3+/- 2.2 kcal?min(-1),
      respectively) (p < 0.05). Gross efficiency was higher at 80 rpm vs. 100 rpm
      during both the 65% (22.8 +/- 1.0 vs. 21.3 +/- 4.5%) and the 80% (23.1 vs. 22.1
      +/- 0.9%) exercise intensities (P< 0.05). Maximal power during the performance
      test (362 +/- 38 watts) was greater at 80 rpm than 100 rpm (327 +/- 27 watts) (p
      < 0.05). Findings suggest that in conditions simulating those seen during
      prolonged competitive cycling, higher cadences (i.e., 100 vs. 80 rpm) are less
      efficient, resulting in greater energy expenditure and reduced peak power output
      during maximal performance. Key PointsWhen competitive cyclists perform prolonged
      exercise that simulates racing conditions (i.e., variable, low-moderate
      submaximal cycling), a higher cadence results in excess energy expenditure and
      lower gross efficiency compared to a lower cadence at the same power
      output.Consequently, maximal power output is reduced during a subsequent exercise
      bout to exhaustion after using a higher cadence.Selection of a lower, more
      energetically optimal cadence during prolonged cycling exercise may allow
      competitive cyclists to enhance maximal performance later in a race. 

PMID- 24570615
TI  - The effectiveness of shin guards used by football players.
AB  - In football, injuries from opponent contact occur commonly in the lower
      extremities. FIFA the world's governing body for football requires players to
      wear shin guards. The aim of this study was to compare the protective
      effectiveness of polypropylene based shin guards with custom-made carbon fiber
      ones. Three commercial polypropylene shin guards (Adidas PredatorTM, Adidas
      UCLTM, and Nike MercurialTM) and two custom-made carbon fiber shin guards were
      examined. The experimental setup had the following parts: 1) A pendulum attached
      a load cell at the tip (CAS Corp., Korea) and a fixed prosthetic foot equipped
      with a cleat to simulate an attacker's foot. 2) An artificial tibia prepared by
      condensed foam and reinforced by carbon fibers protected with soft clothing. 3) A
      multifunctional sensor system (Tekscan Corp., F-Socket System, Turkey) to record
      the impact on the tibia. In the low impact force trials, only 2.79-9.63 % of the
      load was transmitted to the sensors. When comparing for mean force, peak force
      and impulse, both carbon fiber shin guards performed better than the commercial
      ones (Adidas PredatorTM, Adidas UCLTM, and Nike MercurialTM) (p = 0.000). Based
      on these same parameters, the Nike MercurialTM provided better protection than
      the Adidas PredatorTM and the Adidas UCLTM (p = 0.000). In the high impact force
      trials, only 5.16-10.90 % of the load was transmitted to the sensors. For peak
      force and impulse, the carbon fiber shin guards provided better protection than
      all the others. Carbon fiber shin guards possess protective qualities superior to
      those of commercial polypropylene shin guards. Key PointsShin guards decrease the
      risk of serious injuries.Carbon shin guards provide sufficient protection against
      high impact forces.Commercially available Polypropylene based shin guards do not
      provide sufficient protection against high impact forces. 

PMID- 24570616
TI  - Acceleration kinematics in cricketers: implications for performance in the field.
AB  - Cricket fielding often involves maximal acceleration to retrieve the ball. There
      has been no analysis of acceleration specific to cricketers, or for players who
      field primarily in the infield (closer to the pitch) or outfield (closer to the
      boundary). This study analyzed the first two steps of a 10-m sprint in
      experienced cricketers. Eighteen males (age = 24.06 +/- 4.87 years; height = 1.81
      +/- 0.06 m; mass = 79.67 +/- 10.37 kg) were defined as primarily infielders (n =
      10) or outfielders (n = 8). Timing lights recorded 0-5 and 0-10 m time. Motion
      capture measured first and second step kinematics, including: step length; step
      frequency; contact time; shoulder motion; lead and rear arm elbow angle; drive
      leg hip and knee extension, and ankle plantar flexion; swing leg hip and knee
      flexion, and ankle dorsi flexion. A one-way analysis of variance (p < 0.05)
      determined between-group differences. Data was pooled for a Pearson's correlation
      analysis (p < 0.05) to analyze kinematic relationships. There were no differences
      in sprint times, and few variables differentiated infielders and outfielders.
      Left shoulder range of motion related to second step length (r = 0.471). First
      step hip flexion correlated with both step lengths (r = 0.570-0.598), and
      frequencies (r = -0.504--0.606). First step knee flexion related to both step
      lengths (r = 0.528-0.682), and first step frequency (r = -0.669). First step
      ankle plantar flexion correlated with second step length (r = -0.692) and
      frequency (r = 0.726). Greater joint motion ranges related to longer steps.
      Cricketers display similar sprint kinematics regardless of fielding position,
      likely because players may field in the infield or outfield depending on match
      situation. Due to relationships with shoulder and leg motion, and the importance
      and trainability of step length, cricketers should target this variable to
      enhance acceleration. Key PointsRegardless of whether cricketers field
      predominantly in the infield or outfield, they will produce relatively similar
      sprint acceleration kinematics. This is likely due to the fact that cricketers
      will often field in both areas of the cricket ground, depending on the
      requirements of the match.Due to the complexity of sprint acceleration, there
      were relatively few significant correlations between technique variables.
      However, step length had positive relationships with shoulder range of motion,
      swing leg hip and knee flexion, and drive leg ankle plantar flexion.As previous
      research has established the importance of step length to acceleration, as well
      as the trainability of this kinematic variable, training specifically to improve
      step length could lead to enhanced sprint acceleration in cricketers. 

PMID- 24570617
TI  - Factorial validity and internal consistency of the motivational climate in
      physical education scale.
AB  - The aim of the study was to examine the construct validity and internal
      consistency of the Motivational Climate in Physical Education Scale (MCPES). A
      key element of the development process of the scale was establishing a
      theoretical framework that integrated the dimensions of task- and ego involving
      climates in conjunction with autonomy, and social relatedness supporting
      climates. These constructs were adopted from the self-determination and
      achievement goal theories. A sample of Finnish Grade 9 students, comprising 2,594
      girls and 1,803 boys, completed the 18-item MCPES during one physical education
      class. The results of the study demonstrated that participants had highest mean
      in task-involving climate and the lowest in autonomy climate and ego-involving
      climate. Additionally, autonomy, social relatedness, and task- involving climates
      were significantly and strongly correlated with each other, whereas the ego-
      involving climate had low or negligible correlations with the other climate
      dimensions.The construct validity of the MCPES was analyzed using confirmatory
      factor analysis. The statistical fit of the four-factor model consisting of
      motivational climate factors supporting perceived autonomy, social relatedness,
      task-involvement, and ego-involvement was satisfactory. The results of the
      reliability analysis showed acceptable internal consistencies for all four
      dimensions. The Motivational Climate in Physical Education Scale can be
      considered as psychometrically valid tool to measure motivational climate in
      Finnish Grade 9 students. Key PointsThis study developed Motivational Climate in
      School Physical Education Scale (MCPES). During the development process of the
      scale, the theoretical framework using dimensions of task- and ego involving as
      well as autonomy, and social relatedness supporting climates was constructed.
      These constructs were adopted from the self-determination and achievement goal
      theories.The statistical fit of the four-factor model of the MCPES consisting of
      motivational climate factors supporting perceived autonomy, social relatedness,
      task-involvement, and ego-involvement was satisfactory. Additionally, the results
      of the reliability analysis showed acceptable internal consistencies for all four
      dimensions.The results of the study demonstrated that participants had highest
      mean in task-involving climate and the lowest in autonomy climate.Autonomy,
      social relatedness, and task climate were significantly and strongly correlated
      with each other, whereas the ego climate factor had low or negligible
      correlations with the other three factors. 

PMID- 24570618
TI  - Reliability of the dynavisionTM d2 for assessing reaction time performance.
AB  - Recently, the DynavisionTM D2 Visuomotor Training Device (D2) has emerged as a
      tool in the assessment of reaction time (RT); however, information regarding the
      reliability of the D2 have been limited, and to date, reliability data have been
      limited to non- generalizable samples. Therefore, the purpose of this study was
      to establish intraclass correlation coefficients (ICC2,1) for the D2 that are
      generalizable across a population of recreationally active young adults. Forty
      two recreationally active men and women (age: 23.41 +/- 4.84 years; height: 1.72
      +/- 0.11 m; mass: 76.62 +/- 18.26 Kg) completed 6 trials for three RT tasks of
      increasing complexity. Each trial was separated by at least 48-hours. A repeated
      measures ANOVA was used to detect differences in performance across the six
      trials. Intraclass correlation coefficients (ICC2,1) standard error of
      measurement (SEM), and minimal differences (MD) were used to determine the
      reliability of the D2 from the two sessions with the least significant difference
      score. Moderate to strong reliability was demonstrated for visual RT (ICC2,1:
      0.84, SEM: 0.033), and reactive ability in both Mode A and Mode B tasks (Mode A
      hits: ICC2,1: 0.75, SEM: 5.44; Mode B hits: ICC2,1: 0.73, SEM: 8.57). Motor RT
      (ICC2,1: 0.63, SEM: 0.035s) showed fair reliability, while average RT per hit for
      Modes A and B showed moderate reliability (ICC2,1: 0.68, SEM: 0.43 s and ICC2,1:
      0.72, SEM: 0.03 s respectively). It appears that one familiarization trial is
      necessary for the choice reaction time (CRT) task while three familiarization
      trials are necessary for reactive RT tasks. In conclusion, results indicate that
      the DynavisionTM D2 is a reliable device to assess neuromuscular reactivity given
      that an adequate practice is provided. The data presented are generalizable to a
      population of recreationally active young adults. Key PointsThe DynavisionTM D2
      is a light-training reaction device, developed to train sensory motor integration
      through the visual system, offering the ability to assess visual and motor
      reaction to both central and peripheral stimuli, with a capacity to integrate
      increasing levels of cognitive challenge.The DynavisionTM D2 is a reliable
      instrument for assessing reaction time in recreationally active young adults.It
      is recommended that one familiarization trial is necessary for the choice
      reaction time task assessment to learn the test protocol, while three
      familiarization trials are needed for reactive ability in Mode A and Mode B
      before a subsequent reliable baseline score can be established.Significant
      training effects were observed for all reaction time tests and should be taken
      into account with continuous trials. 

PMID- 24570619
TI  - Influence of omega-3 (n3) index on performance and wellbeing in young adults
      after heavy eccentric exercise.
AB  - A clinical study was undertaken to evaluate the associations between the tissue
      levels of omega-3 (N3), also known as the Omega-3 Index (N3 Index), on various
      clinical and quality of life outcomes in healthy young adults after heavy
      eccentric exercise.. To ensure an adequate number of participants with an
      elevated N3 index would be available for comparison to those with a lower N3
      Index, a subgroup of the study participants received N3 dietary supplementation
      (2.7 g.d(-1)) for 30 days prior to the performance of the heavy eccentric
      exercise. The remaining participants received a placebo supplement for the same
      30-day period. After 30 days of supplementation, participants performed an
      eccentric exercise routine and were then measured at baseline (time 0), 24-, 48-,
      72-, and 96 hours respectively on the following outcomes; C-reactive protein
      (CRP) and creatine kinase. Blood lactate levels were analyzed immediately after
      the exercise. Functional measurements of delayed onset of muscle soreness (DOMS),
      extension and torque were also analyzed. Quality of life (QOL) was measured by
      the quantitative questionnaire, the Profile of Mood States Questionnaire (POMS).
      Safety monitoring and analysis of adverse events was continuous throughout the
      study. Differences as demonstrated by a reduction in pain following eccentric
      exercise was experienced at both 72 and 96 hour time points in subjects with a
      higher N3 Index however there were no differences in extension or strength
      between the two groups. There was a significant difference in blood lactate
      levels (p = 0.0309) and improved emotional stability, reflected by the POMS
      questionnaire, in subjects with a higher N3 Index level. There was a
      statistically significant difference in CRP levels in subjects with a higher N3
      Index level at 24 hours and a trend toward significance over 96 hours. There were
      no significant differences in creatine kinase levels and no reported adverse
      events. Subjects with a higher Omega-3 (N3) Index reported less pain related to
      DOMS following heavy exercise at 72 and 96 hours post-exercise. Reduced pain in
      the higher N3 Index Group may be due to an increased concentration of omega-3
      fatty acids in the muscle cell walls, thus triggering a higher elasticity,
      flexibility and lower risk of physical damage to muscle tissue during exercise.
      Serum levels of blood lactate were lower in subjects with a high N3 Index, CRP
      was reduced at 24 hours and POMS scores were improved in high N3 Index subjects
      demonstrating better QOL. No serious adverse events were reported further
      supporting that omega-3 dietary supplementation is safe, bio-available and may
      improve athletic performance and well being in healthy young adults. Key
      PointsOmega-3 index (N3) is elevated after supplementation versus placebo in
      healthy young adultsSubjects with higher N3 index demonstrated reduced DOMS after
      heavy exerciseSubjects with higher N3 index reported better quality of life. 

PMID- 24570620
TI  - Leg strength and lean mass symmetry influences kicking performance in Australian
      football.
AB  - Differential loading patterns during game-based participation may produce or
      exacerbate strength imbalances between the lower limbs. It is currently unknown
      whether such imbalances are functionally beneficial or detrimental to
      performance. This study assessed the influence of lower limb strength and lean
      mass symmetry on kicking accuracy in Australian Football. Thirty-one Australian
      footballers were required to perform a kicking assessment, producing ten drop
      punt kicks over twenty metres to a player target. Athletes were subsequently
      separated into accurate (n = 15) and inaccurate (n = 16) groups, with lower-body
      lean mass assessed using whole body DXA scans, and lower-body strength assessed
      using an isometric protocol. Accurate kickers demonstrated significantly higher
      relative lean mass (~8% to 16%; p = 0. 001 to 0.004) and significantly lower
      relative fat mass (~21% to 40%; p = 0.001 to 0.024) than inaccurate kickers.
      Accurate kickers did not contain any significant difference in lean mass or
      unilateral strength between lower limbs. Inaccurate kickers displayed significant
      asymmetry in lean mass (~3%; p <= 0.003), producing significant imbalances in
      strength (~8%; p <= 0.002) highlighting a deficiency in their support leg.
      Greater relative strength and improved lower limb symmetry in strength and
      muscularity could increase the capacity of an athlete to be technically
      proficient in favour of greater accuracy. Key PointsStrength deficits in the
      support leg may lead to inaccurate kicking outcomes.An asymmetry of 3% in lean
      mass generated an 8% imbalance in leg strength.Greater levels of relative lower
      body strength and muscle mass are associated with improved kicking accuracy
      performance. 

PMID- 24570621
TI  - A multilevel approach to the path to expertise in three different competitive
      settings.
AB  - The objectives of the study were to analyze the deliberate practice variables in
      three different youth competitive sport settings; to analyze the effects of a
      season-long exposure on deliberate practice variables. The study explores three
      contexts in two different sports, soccer and volleyball, and at two competitive
      levels. The athletes fulfilled the questionnaire at the beginning and at the end
      of the season. A multilevel analysis was performed. Forty eight boys aged 15-17
      years (14 from a volleyball club; 14 from an elite volleyball centre; 20 from a
      professional soccer club) participated in the study. The measure was an adapted
      version for soccer and volleyball of the Deliberate Practice Motivation
      Questionnaire, which assesses two dimensions: the will to compete and the will to
      excel. Fewer people in the volleyball group showed a will to excel, the soccer
      group showed an increase in the scores. In will to compete, the three teams
      showed a decrease in their means. The decrease is more pronounced in the will to
      excel but the context effect is not significant. The biggest decrease is shown by
      the elite volleyball team, followed by the club teams. The findings raise
      questions for managers and coaches who look for physical and technical gifted
      young athletes and aim to develop their qualities through a careful planned
      training programme. The insertion in programmes that are believed to foster
      expertise seems to have unexpected consequences. Sport participation cannot rely
      exclusively on an orientation toward expertise, forgetting the autonomy of young
      people to set their goals. Key PointsThe need for the adolescents to focus on
      game performance can be a deterrent for their own perspectives of a career or
      just to have fun.The crucial factor to influence the players' answers seems to be
      the perspective of a rewarding professional career in sport.It is possible that
      young athletes, after a hard season, re-evaluate their priorities and think that
      their dedication to sport did not fit their initial expectations.Managers and
      coaches should be aware of important pedagogical implications, and the
      effectiveness of sport participation cannot rely exclusively on an orientation
      toward expertise. 

PMID- 24570622
TI  - Effects of heat stress on ocular blood flow during exhaustive exercise.
AB  - The hypothesis that heat stress reduces the ocular blood flow response to
      exhaustive exercise was tested by measuring ocular blood flow, blood pressure,
      and end- tidal carbon dioxide partial pressure (PETCO2) in 12 healthy males while
      they performed cycle ergometer exercise at 75% of the maximal heart rate at
      ambient temperatures of 20 degrees C (control condition) and 35 degrees C (heat
      condition), until exhaustion. The blood flows in the retinal and choroidal
      vasculature (RCV), the superior temporal retinal arteriole (STRA) and the
      superior nasal retinal arteriole (SNRA) were recorded at rest and at 6 and 16 min
      after the start of exercise period and at exhaustion [after 16 +/- 2 min (mean +/
      SE) and 24 +/- 3 min of exercise in the heat and control condition,
      respectively]. The mean arterial pressure at exhaustion was significantly lower
      in the heat condition than in the control condition at both 16 min and
      exhaustion. The degree of PETCO2 reduction did not differ significantly between
      the two thermal conditions at either 16 min or exhaustion. The blood flow
      velocity in the RCV significantly increased from the resting baseline value at 6
      min in both thermal conditions (32 +/- 6% and 25 +/- 5% at 20 degrees C and 35
      degrees C, respectively). However, at 16 min the increase in RCV blood flow
      velocity had returned to the resting baseline level only in the heat condition.
      At exhaustion, the blood flows in the STRA and SNRA had decreased significantly
      from the resting baseline value in the heat condition (STRA: -19 +/- 5% and SNRA:
      -30 +/- 6%), and SNRA blood flow was lower than that in the control condition (
      14 +/- 6% vs -30 +/- 6% at 20 degrees C and 35 degrees C, respectively), despite
      the finding that both thermal conditions induced the same reductions in PETCO2
      and vascular conductance. These findings suggested that the heat condition
      decreases or suppresses ocular blood flow via attenuation of pressor response
      during exhaustive exercise. Key PointsThe ocular (retinal and choroidal) blood
      flow response to exhaustive exercise with heat stress is unknown.We hypothesized
      that the heat stress decreases ocular blood flow response to exhaustive exercise,
      since cerebral flow, which is regulated similarly to ocular flow, was reported to
      decrease during heat stress.To test this hypothesis, ocular blood flow was
      measured during exhaustive exercise at 20 degrees C (control condition) and 35
      degrees C (heat condition).At exhaustion in the heat condition, the ocular flow
      response was suppressed or decreased with an attenuated pressor response.It is
      suggested that the heat condition decreases or suppresses the ocular blood flow
      to exhaustive exercise via attenuation of pressor response. 

PMID- 24570623
TI  - A three-dimensional kinematic and kinetic study of the college-level female
      softball swing.
AB  - This paper quantifies and discusses the three-dimensional kinematic and kinetic
      characteristics of the female softball swing as performed by fourteen female
      collegiate amateur subjects. The analyses were performed using a three
      dimensional computer model. The model was driven kinematically from subject
      swings data that were recorded with a multi-camera motion analysis system. Each
      subject used two distinct bats with significantly different inertial properties.
      Model output included bat trajectories, subject/bat interaction forces and
      torques, work, and power. These data formed the basis for a detailed analysis and
      description of fundamental swing kinematic and kinetic quantities. The analyses
      revealed that the softball swing is a highly coordinated and individual three
      dimensional motion and subject-to-subject variations were significant in all
      kinematic and kinetic quantities. In addition, the potential effects of bat
      properties on swing mechanics are discussed. The paths of the hands and the
      centre-of-curvature of the bat relative to the horizontal plane appear to be
      important trajectory characteristics of the swing. Descriptions of the swing
      mechanics and practical implications are offered based upon these findings. Key
      PointsThe female softball swing is a highly coordinated and individual three
      dimensional motion and subject-to-subject variations were significant in all
      kinematic and kinetic quantities.The paths of the grip point, bat centre-of
      curvature, CG, and COP are complex yet reveal consistent patterns among subjects
      indicating that these patterns are fundamental components of the swing.The most
      important mechanical quantity relative to generating bat speed is the total work
      applied to the bat from the batter.Computer modeling of the softball swing is a
      viable means for study of the fundamental mechanics of the swing motion, the
      interactions between the batter and the bat, and the energy transfers between the
      two. 

PMID- 24570624
TI  - Heavy Resistance Training and Supplementation With the Alleged Testosterone
      Booster Nmda has No Effect on Body Composition, Muscle Performance, and Serum
      Hormones Associated With the Hypothalamo-Pituitary-Gonadal Axis in Resistance
      Trained Males.
AB  - The effects of 28 days of heavy resistance training while ingesting the alleged
      testosterone-boosting supplement, NMDA, were determined on body composition,
      muscle strength, serum cortisol, prolactin, and hormones associated with the
      hypothalamo-pituitary- gonadal (HPG) axis. Twenty resistance-trained males
      engaged in 28 days of resistance training 4 times/wk while orally ingesting daily
      either 1.78 g of placebo (PLAC) or NMDA. Data were analyzed with separate 2 x 2
      ANOVA (p < 0.05). Criterion measures involved body composition, muscle strength,
      serum cortisol, prolactin, and gonadal hormone levels [free and total
      testosterone, luteininzing hormome (LH), gonadotrophin releasing hormone (GnRH),
      estradiol], and were assessed before (Day 0) and after (Day 29) resistance
      training and supplementation. No changes were noted for total body water and fat
      mass in response to resistance training (p > 0.05) or supplementation (p > 0.05).
      In regard to total body mass and fat-free mass, however, each was significantly
      increased in both groups in response to resistance training (p < 0.05), but were
      not affected by supplementation (p > 0.05). In both groups, lower-body muscle
      strength was significantly increased in response to resistance training (p <
      0.05); however, supplementation had no effect (p > 0.05). All serum hormones
      (total and free testosterone, LH, GnRH, estradiol, cortisol, prolactin) were
      unaffected by resistance training (p > 0.05) or supplementation (p > 0.05). The
      gonadal hormones and cortisol and prolactin were unaffected by 28 days of NMDA
      supplementation and not associated with the observed increases in muscle strength
      and mass. At the dose provided, NMDA had no effect on HPG axis activity or
      ergogenic effects in skeletal muscle. Key PointsIn response to 28 days of heavy
      resistance training and NMDA supplementation, similar increases in muscle mass
      and strength in both groups occurred; however, the increases were not different
      between supplement groups.The supplementation of NMDA had no preferential effect
      on augmenting testosterone or decreasing estrogen, cortisol, and prolactin.While
      resistance training was effective in increasing muscle mass and strength, it was
      not preferentially due to NMDA supplementation.At the dose provided, NMDA
      supplementation for 28 days combined with resistance training does not increases
      muscle mass and strength due to its ability to elevate endogenous testosterone
      levels and lower cortisol and prolactin when compared to placebo. 

PMID- 24570626
TI  - Optimum projection angle for attaining maximum distance in a rugby place kick.
AB  - This study investigated the effect of projection angle on the distance attained
      in a rugby place kick. A male rugby player performed 49 maximum-effort kicks
      using projection angles of between 20 and 50 degrees . The kicks were recorded by
      a video camera at 50 Hz and a 2 D biomechanical analysis was conducted to obtain
      measures of the projection velocity and projection angle of the ball. The
      player's optimum projection angle was calculated by substituting a mathematical
      expression for the relationship between projection velocity and projection angle
      into the equations for the aerodynamic flight of a rugby ball. We found that the
      player's calculated optimum projection angle (30.6 degrees , 95% confidence
      limits +/- 1.9 degrees ) was in close agreement with his preferred projection
      angle (mean value 30.8 degrees , 95% confidence limits +/- 2.1 degrees ). The
      player's calculated optimum projection angle was also similar to projection
      angles previously reported for skilled rugby players. The optimum projection
      angle in a rugby place kick is considerably less than 45 degrees  because the
      projection velocity that a player can produce decreases substantially as
      projection angle is increased. Aerodynamic forces and the requirement to clear
      the crossbar have little effect on the optimum projection angle. Key PointsThe
      optimum projection angle in a rugby place kick is about 30 degrees .The optimum
      projection angle is considerably less than 45 degrees  because the projection
      velocity that a player can produce decreases substantially as projection angle is
      increased.Aerodynamic forces and the requirement to clear the crossbar have
      little effect on the optimum projection angle. 

PMID- 24570625
TI  - Neuromuscular fatigue during 200 m breaststroke.
AB  - THE AIMS OF THIS STUDY WERE: i) to analyze activation patterns of four upper limb
      muscles (duration of the active and non-active phase) in each lap of 200m
      breaststroke, ii) quantify neuromuscular fatigue, with kinematics and physiologic
      assessment. Surface electromyogram was collected for the biceps brachii, deltoid
      anterior, pectoralis major and triceps brachii of nine male swimmers performing a
      maximal 200m breaststroke trial. Swimming speed, SL, SR, SI decreased from the
      1(st) to the 3(rd) lap. SR increased on the 4(th) lap (35.91 +/- 2.99 stroke.min(
      1)). Peak blood lactate was 13.02 +/- 1.72 mmol.l(-1) three minutes after the
      maximal trial. The EMG average rectified value (ARV) increased at the end of the
      race for all selected muscles, but the deltoid anterior and pectoralis major in
      the 1(st) lap and for biceps brachii, deltoid anterior and triceps brachii in the
      4(th) lap. The mean frequency of the power spectral density (MNF) decreased at
      the 4(th) lap for all muscles. These findings suggest the occurrence of fatigue
      at the beginning of the 2(nd) lap in the 200m breaststroke trial, characterized
      by changes in kinematic parameters and selective changes in upper limb muscle
      action. There was a trend towards a non-linear fatigue state. Key PointsFatigue
      in the upper limbs occurs in different way as it described by 100m swimming
      events.Neuromuscular fatigue was estimated by analyzing the physiological changes
      (high blood lactate concentrations), biomechanical changes in the swimming stroke
      characteristics (decreased in swimming velocity), and by the changes in the EMG
      amplitude and frequency parameters at the end of the swimming bout.The amplitude
      signal of EMG provided by the ARV demonstrated an increase at the end with the
      respect to the beginning for all muscles under study, excepted for the muscle
      deltoid anterior.The mean frequency (MNF) in our study decrease at the end of the
      swimming in the 4(th) lap relative to the 1(st) lap for all muscles under
      observation, along the 200m breaststroke.

PMID- 24570627
TI  - Maximal Voluntary Co-Contraction Training may not Always be Effective for Some
      Leg Muscles.

PMID- 24570629
TI  - Is muscular activity level during abdominal bracing trainable? A comparison study
      between bodybuilders and non-athletes.

PMID- 24570628
TI  - Acoustic analysis of breath sounds as a surrogate for gas exchange thresholds.

PMID- 24570630
TI  - Dupuytren's disease: current state of the art.
AB  - BACKGROUND: This review article critically examines the current literature for
      Dupuytren's disease. METHODS: Five procedures are considered: dermofasciectomy,
      limited fasciectomy, segmental aponeurectomy, needle aponeurotomy, and
      collagenase injection. Studies regarding the efficacy of these treatments focus
      primarily on the initial degree of correction, rate of recurrence, and
      complications. RESULTS: No one treatment has been declared superior and
      substantial controversy exists. Comparison between studies has been hampered by
      the absence of uniform definitions for clinical success and measurable disease
      progression. Traditional post-operative care includes formal therapy and night
      splinting, but recent studies have questioned the value of these adjuncts.
      CONCLUSION: The extent of involvement at which the surgeon should intervene was
      previously well accepted by convention, but as the paradigm shifts towards less
      invasive procedures, treatment may be offered at an earlier stage. Future
      research should be structured to recognize the value-based decision making used
      by patients when selecting treatment.

PMID- 24570631
TI  - Rehabilitation following hand transplantation.
AB  - BACKGROUND: Hand allotransplantation can restore motor, sensory and cosmetic
      functions to upper extremity amputees. Over 70 hand transplant operations have
      been performed worldwide, but there is little published regarding post-hand
      transplant rehabilitation. METHODS: The Brigham and Women's Hospital (BWH) Hand
      Transplantation Team's post-hand transplant rehabilitation protocol is presented
      here. The protocol must be modified to address each transplant recipient's unique
      needs. It builds on universally used modalities of hand rehabilitation such as
      splinting, edema and scar management, range of motion exercises, activities of
      daily living training, electrical stimulation, cognitive training and
      strengthening. RESULTS: The BWH hand transplant rehabilitation protocol consists
      of four phases with distinct goals, frequency, and modalities. (1) Pre-operative:
      functional assessments are completed and goals and expectations of
      transplantation are established. (2) Initial post-operative (post-operative weeks
      1-2): hand protection, minimization of swelling, education, and discharge. (3)
      Intermediate (post-operative weeks 2-8): therapy aims to prevent and/or decrease
      scar adhesion, increase tensile strength, flexibility and function, and prevent
      joint contractures. (4) Late (from 8 weeks forward): maximization of function and
      strength, and transition to routine activities. The frequency of rehabilitation
      therapy decreases gradually from the initial to late phases. CONCLUSIONS:
      Rehabilitation therapy after hand transplantation follows a progressive increase
      in activity in parallel with wound healing and nerve regeneration. Careful
      documentation of progress and outcomes is essential to demonstrate the utility of
      interventions and to optimize therapy protocols.

PMID- 24570632
TI  - Metacarpal fractures: treatment and complications.
AB  - Metacarpal fractures comprise between 18-44 % of all hand fractures. Non-thumb
      metacarpals account for around 88 % of all metacarpal fractures, with the fifth
      finger most commonly involved [19]. The majority of metacarpal fractures are
      isolated injuries, which are simple, closed, and stable. While many metacarpal
      fractures do well without surgery, there is a paucity of literature and
      persistent controversy to guide the treating physician on the best treatment
      algorithm. The purpose of this article is to review non-thumb metacarpal anatomy
      and treatment protocols for nonoperative management of stable fractures, and
      compare existing literature on surgical techniques for treatment of acute
      fractures and complications. 

PMID- 24570633
TI  - A hand surgeon's guide to common onychodystrophies.
AB  - The human fingernail contributes to the precise dexterity of the fingers,
      enhances sensibility, allows manipulation of fine objects, and shields the
      fingertip from traumatic injury. Nail abnormalities are a common incidental
      finding in the course of a hand surgeon's daily practice. These abnormalities may
      be clues to systemic, dermatologic, traumatic, and infectious processes that
      would benefit from further evaluation and treatment. The purpose of this review
      is to discuss common nail dystrophies and their related diagnoses. 

PMID- 24570634
TI  - Surgeon perspectives on alternative nerve repair techniques.
AB  - BACKGROUND: Over the past five decades, microsuturing has been established as the
      "gold standard" for nerve repair. Alternative techniques such as fibrin glue,
      protein "welds", and nerve connectors have been met with variable enthusiasm.
      While advancements in this area continue, there is little data on surgeon
      attitude and acceptance of these new techniques. METHODS: A short questionnaire
      was electronically distributed to the members of the American Society for Surgery
      of the Hand and the American Association of Hand Surgery. Survey questions
      ascertained demographic information of participants (specialty, years in
      practice, practice setting, etc.), attitudes about current techniques (what
      techniques currently used, why, etc.), and attitudes about new techniques
      (openness to trying, factors that would persuade for/against, etc.). The surveys
      were distributed and administered online. Data gathered from responses was
      analyzed looking for general trends and stratified based on demographic data.
      RESULTS: The majority of responders still consider microsuturing as the gold
      standard for primary nerve repair, and it is by far the most utilized technique.
      However, over 90 % also reported that they either currently use or would consider
      using alternate techniques. Common barriers to utilizing alternate techniques
      included lack of data regarding outcomes and unfamiliarity with new techniques.
      Only 40 % of responders considered metal as safe around nerves, but most consider
      absorbable polymers safe. None of the underlying demographic variables including
      years in practice, number of nerve repair surgeries performed per month, practice
      setting, or specialty affected these general trends. CONCLUSIONS: Most surgeons
      performing nerve repairs prefer suturing as their primary repair technique, but a
      vast majority is open to utilizing alternate repair techniques, especially those
      that improve outcomes with a faster and easier procedure. While not able to
      direct clinical practice guidelines, this study can be used to direct focus and
      funding of further alternate nerve repair techniques.

PMID- 24570635
TI  - Prospective randomized comparison of single-incision and two-incision carpal
      tunnel release outcomes.
AB  - BACKGROUND: This study analyzes both the subjective and objective symptom and
      functional outcomes of patients who underwent either traditional single-incision
      or two-incision carpal tunnel release (CTR). METHODS: From 2008 to 2009, patients
      with isolated carpal tunnel syndrome were randomized to undergo either single
      incision or two-incision CTR by a single surgeon at a university medical center.
      Pre-operatively, participants completed a Disabilities of the Arm, Shoulder, and
      Hand (DASH) Questionnaire, Brigham and Women's Carpal Tunnel Questionnaire
      (BWCTQ), as well as grip and pinch strength and Semmes-Weinstein monofilament
      sensation testing. At 2 weeks, 6 weeks and at least 6 months post-operatively,
      these measurements were repeated along with assessment of scar tenderness and
      pillar pain. Data were analyzed using SPSS version 20 software to perform non
      parametric tests and Pearson's correlations. Significance was set at p = 0.05.
      RESULTS: There was no statistically significant difference between the single-
      and two-incision CTR groups with respect to pre- and post-operative DASH scores,
      BWCTQ scores, grip strength, pinch strength, scar tenderness, or pillar pain. The
      only statistically significant difference was improved sensation by Semmes
      Weinstein in the single-incision group in the second finger at 6 weeks post
      operatively and in the third finger at 6 months post-operatively. CONCLUSIONS:
      The preservation of the superficial nerves and subcutaneous tissue between the
      thenar and hypothenar eminences may account for reports of less scar tenderness
      and pillar pain among recipients of two-incision CTR compared to single-incision
      CTR in the early post-operative period. However, there is similar post-operative
      recovery and improvement in grip and pinch strength and sensation after 6+ months
      post-operatively.

PMID- 24570636
TI  - Concomitant endoscopic carpal and cubital tunnel release: safety and efficacy.
AB  - BACKGROUND: When performed alone, endoscopic carpal tunnel release and endoscopic
      cubital tunnel release are safe and effective surgical options for the treatment
      of carpal and cubital tunnel syndromes, respectively. However, there is currently
      no literature that describes the performance of both procedures concomitantly. We
      describe the results of 17 cases in which dual endoscopic carpal and cubital
      tunnel releases were performed for the treatment of concurrent carpal and cubital
      tunnel syndromes. METHODS: A retrospective review of all patients in a single
      surgeon practice that presented with concomitant ipsilateral carpal and cubital
      tunnel syndromes was performed. Within an 8-month period, 17 patients had
      undergone 19 concomitant ipsilateral endoscopic carpal and cubital tunnel
      releases after failing conservative treatment. Pre- and postoperative
      measurements included subjective numbness/tingling; subjective pain; manual
      muscle testing of the abductor pollicis brevis (APB), intrinsics, and flexor
      digitorum profundus (FDP); static two-point discrimination; quick-DASH
      (Disabilities of the Arm, Shoulder and Hand) scores; grip strength; chuck pinch
      strength; and key pinch strength. Complete data are available for 15 patients and
      17 total procedures. RESULTS: Thirteen male and four female patients (average age
      of 50.5) underwent dual endoscopic cubital and carpal tunnel release. Two
      patients were lost to follow-up and eliminated from data analysis. Pre- and
      postoperative comparisons were completed for median DASH scores, grip strength,
      chuck pinch strength, and key pinch strength at their preoperative visit and at
      12 weeks. DASH scores improved significantly from a median of 67.5 to 16 (p =
      0.002), grip strengths improved from 42 to 55.0 lbs (p = 0.30), chuck pinch
      strengths improved significantly from 11 to 15.5 lbs (p = 0.02), and key pinch
      strengths increased significantly from 13 to 18 lbs (p = 0.003). Average static
      two-point discrimination decreased from 5.9 to 4.8 mm. In terms of pain, 82 % of
      patients had complete resolution of pain, and the remaining 18 % experienced pain
      only with strenuous activity. In terms of numbness/tingling, 100 % of patients
      had complete resolution of median nerve symptoms; 88 % of patients had
      substantial improvement of numbness and tingling symptoms, and 12 % had residual
      ulnar nerve symptoms. In terms of muscle strength, 92 % of patients had
      improvement to 5/5 APB strength, while 100 % of patients had improvement to 5/5
      intrinsic and FDP strengths. Two minor complications occurred, including one
      superficial hematoma and one superficial cellulitis. CONCLUSIONS: Preliminary
      data demonstrate that dual endoscopic carpal and cubital tunnel release is a safe
      and effective treatment option for patients who present with concurrent cubital
      and carpal tunnel syndromes recalcitrant to non-surgical management.
      Postoperative results and complications are comparable to endoscopic carpal and
      cubital tunnel releases performed alone.

PMID- 24570637
TI  - Carpal tunnel release using the Paine retinaculotome inserted through a palmar
      incision.
AB  - BACKGROUND: Carpal tunnel syndrome (CTS) is the most commonly diagnosed and
      treated entrapment neuropathy. There is no consensus regarding the optimal
      technique for carpal tunnel release. The objective of this study is to
      demonstrate the surgical treatment of CTS by a small palmar incision and
      utilization of Paine retinaculotome to divide the transverse carpal ligament.
      METHODS: In this technical note, we describe the use of a retinaculotome
      described by Paine in 1955, through a palmar approach. DISCUSSION: Open,
      minimally invasive and endoscopic surgical techniques have all been described as
      treatment options for CTS, and short-term success with these methods is well
      established. During the last decade, less invasive techniques have been developed
      in order to reduce the incidence of pillar pain and tender scars. We have used a
      mini-palmar incision and the Paine retinaculotome for carpal tunnel release since
      1994. The goals of surgery are to create a small incision that permits a patient
      to have early motion and return to activity. CONCLUSION: After many years, no
      permanent nerve or vascular damage has been reported. This method has
      demonstrated itself to be efficient and safe in the treatment of the carpal
      tunnel syndrome.

PMID- 24570638
TI  - Effects of multiple injections of hypertonic dextrose in the rabbit carpal
      tunnel: a potential model of carpal tunnel syndrome development.
AB  - BACKGROUND: This study investigated the effects of a series of four hypertonic
      dextrose injections on the subsynovial connective tissue (SSCT) and median nerve
      within the carpal tunnel of a rabbit model. METHODS: Twenty New Zealand white
      rabbits were used. One forepaw carpal tunnel was randomly injected with 0.1 ml of
      10 % dextrose solution. The contralateral forepaw was injected with a similar
      amount of saline. This injection was made once per week for 4 weeks. The animals
      were killed at 16 weeks after the initial injection and were evaluated by
      electrophysiology (EP), SSCT mechanical testing, and histology. RESULTS:
      Mechanical testing revealed significantly greater ultimate load and energy
      absorption in the dextrose injection group compared to the saline injection group
      (P < 0.05). Histological evaluation revealed SSCT fibrosis and thickening and
      edema in the median nerve bundles in the dextrose injection group. There was a
      prolongation in the latency of the EP test in the dextrose injection group (P =
      0.08). CONCLUSIONS: Previous studies had shown that one or two injections of 10 %
      dextrose could induce moderate SSCT fibrosis and mild EP changes without nerve
      histology changes. In this study, we have shown that higher doses create more
      severe fibrosis and, most importantly, more severe neuropathy, suggesting a dose
      response effect, and confirming this as a potentially useful animal model for
      researching the etiology and treatment of carpal tunnel syndrome.

PMID- 24570639
TI  - A role delineation study of hand surgery in the USA: assessing variations in
      fellowship training and clinical practice.
AB  - BACKGROUND: We examined the fellowship experience of hand surgeons in the USA to
      identify gaps and variations in exposure to essential skills and knowledge during
      hand fellowship. METHODS: We conducted a web-based survey of the entire American
      Society for Surgery of the Hand and American Association for Hand Surgery
      membership. We inquired about the level of exposure received to 170 knowledge
      topics and procedures during fellowship. We used factor analysis to group the
      knowledge topics and procedures into 79 scales of related items and calculated
      mean exposure ratings for each scale. We compared the ratings between graduates
      of plastic surgery (PS) and orthopedic surgery (OS) Residency Review Committee
      (RRC)-accredited fellowships. RESULTS: Our response rate was 21 % (n = 562).
      Plastic surgery RRC-accredited fellowship graduates reported inadequate exposure
      for proficiency in 22 % (17/79) of the knowledge topic and procedure scales
      whereas graduates of OS RRC-accredited fellowships reported inadequate exposure
      for proficiency in 10 % (8/79) of the scales. Moreover, 11 and 21 % of graduates
      from PS RRC-accredited fellowships reported receiving no exposure in distal
      radius/ulna and forearm conditions, respectively, whereas only 1 and 2 % of
      graduates from OS RRC-accredited fellowships reported receiving no exposure in
      the same domains, respectively. CONCLUSIONS: Hand surgeons reported significant
      variations in exposure to essential skills and knowledge. Additionally, in a
      considerable number of knowledge topics and procedures, a majority of
      participants in both groups reported what they perceived as inadequate or no
      exposure during their hand surgery fellowship.

PMID- 24570640
TI  - The correlation of phrases and feelings with disability.
AB  - BACKGROUND: Patient expressions reflect disability and psychological factors. The
      aim of this study was to list common phrases and feelings in hand surgery
      practice and to prospectively study the correlation of these phrases and to
      correlate them with possible associated feelings and disability. METHODS: Eighty
      three patients completed the short version of the disabilities of arm, shoulder
      and hand (QuickDASH) questionnaire to measure disability, the pain self-efficacy
      questionnaire (PSEQ) to study coping, and a pain scale. The patients also
      completed the phrases and feelings questionnaire, which list verbal expressions
      patients often use. Pearson's correlation was used to test the correlation of
      continuous variables, and independent t test and one-way ANOVA were used for
      categorical variables. All variables with p < 0.08 were inserted in a
      multivariable regression. RESULTS: There was a large correlation between the
      individual phrases and feelings questions with PSEQ and QuickDASH. The best model
      for the combined phrases questionnaire included pain, PSEQ, smoking, and other
      pain conditions. The best model for the combination of all the feelings questions
      included PSEQ, pain, and marital status. The best model for QuickDASH included
      phrases, PSEQ, prior treatment, and working status, with phrases being the
      strongest factor. CONCLUSIONS: Patients use specific phrases that indicate the
      magnitude of their disability and the effectiveness of their coping strategies.
      Providers should respond to these phrases by empathetically acknowledging these
      aspects of the human illness experience.

PMID- 24570641
TI  - The association of education level on outcome after distal radius fracture.
AB  - BACKGROUND: Socioeconomic factors have been found to be predictors of outcome for
      other ailments. The purpose of this study was to evaluate the association of
      patient education level on pain and disability after distal radius fracture.
      METHODS: A series of patients with distal radius fractures (n = 335) were
      enrolled into a prospective research registry. Standard demographic information
      was obtained from patients, including a five-value categorical education
      variable. After treatment with closed reduction, external fixation, or internal
      fixation patients were evaluated for pain, function (Disability of the Arm,
      Shoulder, and Hand score [DASH]), range of motion (ROM), and grip strength at
      standard intervals until 12 months post-injury. A series of linear mixed effects
      models were developed to evaluate the relationship between time from injury and
      education level with each of the outcomes measured. RESULTS: Complete demographic
      and 12-month follow-up data were available on 227 patients (75 %). There were
      neither group differences in mode of injury, severity, nor treatment modality
      after stratification by education level. Mixed effects model analyses revealed a
      significant linear association between level of education and measured outcomes
      at each follow-up point. Overall, each increase in education level demonstrated a
      doubling of improvement in pain, ROM, grip strength, and DASH score. CONCLUSIONS:
      Outcome of distal radius fracture depends on acute care and follow-up
      rehabilitation; however, patient-related factors indicative of socioeconomic
      status are becoming increasingly relevant as predictors of outcome and should be
      considered by the orthopaedist.

PMID- 24570642
TI  - The impact of demographic factors and comorbidities on distal radius fracture
      outcomes.
AB  - BACKGROUND: Despite the prevalence and consequences of distal radius fracture
      (DRF), there is limited research that analyzes the effects of demographic factors
      and comorbidities as they relate to pain, perceived disability, and functional
      outcomes. METHODS: All data for this study were examined retrospectively within
      an established clinical database. Patients with DRF were evaluated during their
      first and final visits with a criterion-based numeric pain scale (CR12), the
      Disability of the Arm, Shoulder, and Hand (DASH) questionnaire, and a global rate
      of change scale to assess outcomes of pain, perceived disability, and function,
      respectively. RESULTS: The number of days between injury and initial therapy
      evaluation were inversely correlated with changes in perceived pain and perceived
      disability (r = -0.315, p = 0.000; r = -0.348, p = 0.000). In addition, moderate
      and statistically significant correlations were noted between work status and
      average CR12 and DASH scores at final re-evaluation (r = 0.392, p = 0.000, r =
      0.473, p = 0.000). No significant relationships were noted between additional
      demographic factors or comorbidities and pain, perceived disability, or function
      during statistical analysis. CONCLUSIONS: Patients without diabetes,
      hypertension, or depression and those who were not smokers had better outcomes in
      terms of pain, perceived disability, and function in this study. In addition,
      earlier timing of initial evaluation after injury and full duty work status were
      significantly related to improvement in pain and perceived disability. Timing of
      initiation of therapy and return to work are suggested as avenues for future
      research.

PMID- 24570643
TI  - MRI detection of forearm soft tissue injuries with radial head fractures.
AB  - BACKGROUND: This study aims to evaluate the incidence of forearm soft tissue
      abnormalities associated with radial head fracture severity based on the Mason
      classification system. METHODS: Eighteen patients (age 18-45 years) were
      prospectively evaluated with elbow radiographs and magnetic resonance imaging
      (MRI) following longitudinal forearm trauma. MRI was performed within 10 days of
      the initial injury. Radiographs and MR images were evaluated in a blinded fashion
      by two musculoskeletal radiologists. RESULTS: Thirteen of 18 patients presented
      with Mason type I radial head fractures. In all patients with Mason type I
      fractures, the interosseous membrane (IOM) was intact. Two patients had Mason
      type II fractures with associated partial and compete tearing of the IOM and
      three patients had Mason type III fractures with complete tearing of the IOM.
      Edema was noted in the pronator quadratus in six of 13 type I injuries and seen
      in all type II and III injuries. No structural forearm soft tissue abnormalities
      were present in patients with Mason type I injuries. The presence of edema within
      the pronator quadratus correlated with distal forearm pain. CONCLUSIONS: The
      severity of radial head fracture correlates with longitudinal forearm injury
      evidenced by the presence of IOM tearing. The findings suggest patients with
      Mason type II or III fractures of the radial head should undergo further
      evaluation of the forearm for associated soft tissue injuries. Edema within the
      pronator quadratus was present following forearm trauma regardless of the
      severity of fracture and was related to symptomatic forearm pain.

PMID- 24570644
TI  - Reconstruction of swan neck deformities after proximal interphalangeal joint
      arthroplasty.
AB  - BACKGROUND: The authors report the use of a single slip of the flexor digitorum
      superficialis (FDS) as a hemitenodesis through the A2 pulley in treating swan
      neck deformities after previous unconstrained proximal interphalangeal joint
      (PIP) arthroplasty. METHODS: A retrospective chart review was undertaken to
      identify non-constrained PIP joint arthroplasties that underwent a subsequent
      soft tissue hemitenodesis for swan neck deformities. The range of motion (ROM),
      implant design, preoperative diagnosis, and surgical approach were collected. The
      Michigan Hand Outcomes Questionnaire and patient satisfaction questionnaire were
      collected. RESULTS: There were 12 patients with 14 procedures reviewed. There
      were seven surface replacement arthroplasties (SRA) (cobalt chrome on
      polyethylene) and eight pyrocarbon prostheses. The primary diagnosis for the
      initial joint arthroplasty was osteoarthritis (8), post-traumatic (2), and
      rheumatoid arthritis (5). The primary dorsal approach was a longitudinal split in
      eleven cases, Chamay in two, and unknown in one case. Nine of the 14 revision
      procedures had a concomitant dorsal approach to the joint. The average final
      position intraoperatively was 24.2 degrees  of flexion (range 15 degrees -40
      degrees ). Final ROM was 39 degrees  with average follow-up of 30 months. The
      average postoperative radiographic position was 20.3 degrees  flexion with an
      average of 24.8 degrees  hyperextension preoperatively. There was one failure
      secondary to implant loosening requiring fusion. DISCUSSION: For patients with a
      swan neck deformity after PIP arthroplasty, a FDS hemitenodesis provides a
      treatment option with a low revision rate, retained motion, and maintenance of
      the original implant with no shortening of the digit.

PMID- 24570645
TI  - The Effect of Pulley Reconstruction on Maximum Flexion, Bowstringing, and Gliding
      Coefficient in the Setting of Zone II Repair of FDS and FDP: a Cadaveric
      Investigation.
AB  - PURPOSE: The purpose of this experiment was to determine the effect of A2 pulley
      reconstruction on gliding coefficient (GC), bowstringing, and proximal
      interphalangeal (PIP) joint maximum flexion angle after zone II repair of flexor
      digitorum superficialis (FDS) and flexor digitorum profundus (FDP) lacerations.
      METHODS: Fresh frozen cadaver forearms were mounted, and the wrist and MCP joints
      fixed. FDS and FDP tendons were dissected free, and sequential loads were applied
      while digital images were captured. The dissected digit with intact native A2
      pulley, FDS, and FDP tendons was used as the control (group 1). Zone II
      lacerations followed by four-stranded repair of FDP plus epitendinous suture and
      repair of FDS were then performed, and the data recorded (group 2). A2 pulley
      excision and reconstruction with a loop of palmaris longus autograft was then
      completed and the specimens sequentially loaded and photographed (group 3). Using
      the digital images, GC, bowstringing, and maximum flexion angle were calculated.
      RESULTS: No difference in maximum flexion angle was observed across the three
      testing conditions. Zone II laceration and subsequent FDS and FDP tendon repair
      significantly increased the GC for group 2 specimens; however, pulley
      reconstruction alleviated some of this increase for group 3. Bowstringing was
      significantly greater after pulley reconstruction, with a mean increase of 1.9 mm
      at maximum flexion for group 3 specimens relative to group 1 controls.
      DISCUSSION: Strong flexor tendon repairs are needed to prevent gap formation and
      subsequent triggering; however, the increased bulk from these large repairs can
      itself produce deleterious triggering, as well as tendon abrasion. Pulley
      reconstruction, in the setting FDP and FDS repair (group 3), significantly
      reduced the GC relative to tendon repair alone (group 2). While bowstringing was
      significantly greater after pulley reconstruction (group 3), it averaged only 1.9
      mm over group 1 specimens and did not compromise maximum flexion angle compared
      to the uninjured controls (group 1) or the isolated tendon repair digits (group
      2).

PMID- 24570646
TI  - Importance of proximal A2 and A4 pulleys to maintaining kinematics in the hand: a
      biomechanical study.
AB  - PURPOSE: The A2 and A4 pulleys have been shown to be important in finger flexor
      tendon function. Other authors have suggested either reconstruction or venting of
      portions of these pulleys in an attempt to preserve finger function in certain
      clinical situations. This study examines the effects of partial incision of these
      pulleys on finger flexion kinematics and biomechanics. METHODS: The index and
      ring fingers of 16 cadaveric hands were studied. The flexor digitorum profundus
      tendon was isolated and attached to a computer driven servo-motor. Micro
      potentiometers measured flexion angles of the metacarpophalangeal, proximal inter
      phalangeal and distal inter-phalangeal joints. Joint inertial torques were
      calculated making use of this experimental kinematic data. RESULTS: Proximal 50 %
      incisions of either the A2 or the A4 pulleys resulted in a statistically
      significant decrease in overall finger motion. This effect was greatest in the
      proximal inter-phalangeal joint, with a decrease in joint motion, as well as an
      earlier time to initiation of motion. These changes in finger motion were more
      pronounced with A2 pulley incision than they were with A4 pulley incision, but
      the changes were statistically significant in either case. No significant changes
      in joint inertial torques were shown. CONCLUSIONS: Our data provides evidence to
      the importance of the proximal portions of the A2 and A4 pulleys, and may support
      partial distal incision of these pulleys in certain clinical situations.

PMID- 24570647
TI  - Utility of MRI for diagnosing complete tears of the collateral ligaments of the
      metacarpophalangeal joints of the lesser digits.
AB  - BACKGROUND: MRI has been shown to be highly accurate in assessing collateral
      ligament injuries of the metacarpophalangeal joint (MPJ) of the thumb. The
      purpose of this study is to evaluate the accuracy of MRI for diagnosing
      collateral ligament tears of the MPJ of the fingers. Our hypothesis is that MRI
      would accurately detect complete tears of collateral ligaments of the lesser
      digit MPJs. METHODS: We retrospectively evaluated 22 digits in 20 patients
      undergoing finger MPJ collateral ligament repair. All patients had preoperative
      MRI scans. The findings on preoperative imaging studies were compared to the
      intraoperative findings. RESULTS: All patients had surgically confirmed complete
      tears of the collateral ligament in question. In 8 of 22 MRI scans (36 %), the
      preoperative imaging study was inaccurate. Of these eight patients, MRI was
      interpreted as no tear in one and a partial tear in seven. The sensitivity of MRI
      for diagnosing a complete tear was 64 %. In all three digits in which 3-T MRI
      scanning was utilized and documented, the preoperative imaging results did not
      correlate with the intraoperative findings. CONCLUSIONS: Although MRI can be
      considered a useful adjunct to evaluating patients with collateral ligament
      injuries of the fingers, the sensitivity is poor and the imaging results can
      underestimate the extent of injury. In light of this, the emphasis for
      determining appropriate course of treatment remains on history and mechanism of
      injury, physical examination, and patient disability.

PMID- 24570648
TI  - Computed tomography for suspected scaphoid fractures: comparison of reformations
      in the plane of the wrist versus the long axis of the scaphoid.
AB  - BACKGROUND: Definitive diagnosis of occult scaphoid fractures remains difficult.
      We tested the null hypothesis that, for diagnosis of true fractures among
      suspected scaphoid fractures, computed tomography (CT) reformations along the
      long axis of the scaphoid have the same accuracy as reformations made relative to
      the anatomical planes of the wrist. METHODS: In a prospective trial, 34 patients
      with a suspected scaphoid fracture underwent CT scanning within 10 days after
      trauma. CT reformations along the long axis of the scaphoid (CT-scaphoid) and
      along planes relative to the wrist (CT-wrist) were made. We used radiographs
      obtained 6 weeks after injury as the reference standard for a true fracture. A
      blinded panel including two surgeons and one radiologist came to a consensus
      diagnosis for each reformation plane. RESULTS: The reference standard showed six
      fractures of the scaphoid (prevalence, 18 %). Using CT-wrist, a scaphoid fracture
      was diagnosed in five patients (15 %), with three false positive, four false
      negative and two true positive diagnoses. Using CT-scaphoid, a scaphoid fracture
      was diagnosed in five patients (15 %), with one false positive, two false
      negative and four true positive results. Sensitivity, specificity and accuracy
      were 33, 89 and 79 % for CT-wrist and 67, 96 and 91 % for CT-scaphoid,
      respectively. This resulted in positive predictive values of 36 % for CT-wrist
      and 76 % for CT-scaphoid. Negative predictive values were 87 % for CT-wrist and
      94 % for CT-scaphoid. No significant differences were found with the number of
      patients available. CONCLUSIONS: For diagnosis of true fractures among suspected
      scaphoid fractures, the diagnostic performance characteristics of CT scans
      reformatted along the long axis of the scaphoid were better than CT scans in the
      planes of the wrist, but the differences were not significant.

PMID- 24570649
TI  - Idiopathic avulsion of the flexor pollicis longus: Case report and review of the
      literature.

PMID- 24570650
TI  - Oral smoothened inhibitor for advanced basal cell carcinoma of the hand: a case
      report.

PMID- 24570651
TI  - Review of 'The importance of pronator quadratus repair in the treatment of distal
      radius fractures with volar plating'.

PMID- 24570652
TI  - Asynchronous visual event-based time-to-contact.
AB  - Reliable and fast sensing of the environment is a fundamental requirement for
      autonomous mobile robotic platforms. Unfortunately, the frame-based acquisition
      paradigm at the basis of main stream artificial perceptive systems is limited by
      low temporal dynamics and redundant data flow, leading to high computational
      costs. Hence, conventional sensing and relative computation are obviously
      incompatible with the design of high speed sensor-based reactive control for
      mobile applications, that pose strict limits on energy consumption and
      computational load. This paper introduces a fast obstacle avoidance method based
      on the output of an asynchronous event-based time encoded imaging sensor. The
      proposed method relies on an event-based Time To Contact (TTC) computation based
      on visual event-based motion flows. The approach is event-based in the sense that
      every incoming event adds to the computation process thus allowing fast avoidance
      responses. The method is validated indoor on a mobile robot, comparing the event
      based TTC with a laser range finder TTC, showing that event-based sensing offers
      new perspectives for mobile robotics sensing. 

PMID- 24570654
TI  - MicroRNAs in brain development and function: a matter of flexibility and
      stability.
AB  - Fine-tuning of gene expression is a fundamental requirement for development and
      function of cells and organs. This requirement is particularly obvious in the
      nervous system where originally common stem cell populations generate thousands
      of different neuronal and glial cell types in a temporally and quantitatively
      perfectly orchestrated manner. Moreover, after their generation, young neurons
      have to connect with pre-determined target neurons through the establishment of
      functional synapses, either in their immediate environment or at distance.
      Lastly, brain function depends not only on static circuitries, but on plastic
      changes at the synaptic level allowing both, learning and memory. It appears
      evident that these processes necessitate flexibility and stability at the same
      time. These two contrasting features can only be achieved by complex molecular
      networks, superposed levels of control and tight interactions between regulatory
      mechanisms. Interactions between microRNAs and their target mRNAs fulfill these
      requirements. Here we review recent literature dealing with the involvement of
      microRNAs in multiple aspects of brain development and connectivity. 

PMID- 24570653
TI  - Autonomic regulation of brown adipose tissue thermogenesis in health and disease:
      potential clinical applications for altering BAT thermogenesis.
AB  - From mouse to man, brown adipose tissue (BAT) is a significant source of
      thermogenesis contributing to the maintenance of the body temperature homeostasis
      during the challenge of low environmental temperature. In rodents, BAT
      thermogenesis also contributes to the febrile increase in core temperature during
      the immune response. BAT sympathetic nerve activity controlling BAT thermogenesis
      is regulated by CNS neural networks which respond reflexively to thermal afferent
      signals from cutaneous and body core thermoreceptors, as well as to alterations
      in the discharge of central neurons with intrinsic thermosensitivity.
      Superimposed on the core thermoregulatory circuit for the activation of BAT
      thermogenesis, is the permissive, modulatory influence of central neural networks
      controlling metabolic aspects of energy homeostasis. The recent confirmation of
      the presence of BAT in human and its function as an energy consuming organ have
      stimulated interest in the potential for the pharmacological activation of BAT to
      reduce adiposity in the obese. In contrast, the inhibition of BAT thermogenesis
      could facilitate the induction of therapeutic hypothermia for fever reduction or
      to improve outcomes in stroke or cardiac ischemia by reducing infarct size
      through a lowering of metabolic oxygen demand. This review summarizes the central
      circuits for the autonomic control of BAT thermogenesis and highlights the
      potential clinical relevance of the pharmacological inhibition or activation of
      BAT thermogenesis. 

PMID- 24570655
TI  - Astrocytes expressing mutant SOD1 and TDP43 trigger motoneuron death that is
      mediated via sodium channels and nitroxidative stress.
AB  - Amyotrophic lateral sclerosis (ALS) is a fatal paralytic disorder caused by
      dysfunction and degeneration of motor neurons. Multiple disease-causing
      mutations, including in the genes for SOD1 and TDP-43, have been identified in
      ALS. Astrocytes expressing mutant SOD1 are strongly implicated in the
      pathogenesis of ALS: we have shown that media conditioned by astrocytes carrying
      mutant SOD1(G93A) contains toxic factor(s) that kill motoneurons by activating
      voltage-sensitive sodium (Na v ) channels. In contrast, a recent study suggests
      that astrocytes expressing mutated TDP43 contribute to ALS pathology, but do so
      via cell-autonomous processes and lack non-cell-autonomous toxicity. Here we
      investigate whether astrocytes that express diverse ALS-causing mutations release
      toxic factor(s) that induce motoneuron death, and if so, whether they do so via a
      common pathogenic pathway. We exposed primary cultures of wild-type spinal cord
      cells to conditioned medium derived from astrocytes (ACM) that express SOD1 (ACM
      SOD1(G93A) and ACM-SOD1(G86R)) or TDP43 (ACM-TDP43(A315T)) mutants; we show that
      such exposure rapidly (within 30-60 min) increases dichlorofluorescein (DCF)
      fluorescence (indicative of nitroxidative stress) and leads to extensive
      motoneuron-specific death within a few days. Co-application of the diverse ACMs
      with anti-oxidants Trolox or esculetin (but not with resveratrol) strongly
      improves motoneuron survival. We also find that co-incubation of the cultures in
      the ACMs with Na v channel blockers (including mexiletine, spermidine, or
      riluzole) prevents both intracellular nitroxidative stress and motoneuron death.
      Together, our data document that two completely unrelated ALS models lead to the
      death of motoneuron via non-cell-autonomous processes, and show that astrocytes
      expressing mutations in SOD1 and TDP43 trigger such cell death through a common
      pathogenic pathway that involves nitroxidative stress, induced at least in part
      by Na v channel activity. 

PMID- 24570657
TI  - A spiking neural network model of self-organized pattern recognition in the early
      mammalian olfactory system.
AB  - Olfactory sensory information passes through several processing stages before an
      odor percept emerges. The question how the olfactory system learns to create odor
      representations linking those different levels and how it learns to connect and
      discriminate between them is largely unresolved. We present a large-scale network
      model with single and multi-compartmental Hodgkin-Huxley type model neurons
      representing olfactory receptor neurons (ORNs) in the epithelium, periglomerular
      cells, mitral/tufted cells and granule cells in the olfactory bulb (OB), and
      three types of cortical cells in the piriform cortex (PC). Odor patterns are
      calculated based on affinities between ORNs and odor stimuli derived from physico
      chemical descriptors of behaviorally relevant real-world odorants. The properties
      of ORNs were tuned to show saturated response curves with increasing
      concentration as seen in experiments. On the level of the OB we explored the
      possibility of using a fuzzy concentration interval code, which was implemented
      through dendro-dendritic inhibition leading to winner-take-all like dynamics
      between mitral/tufted cells belonging to the same glomerulus. The connectivity
      from mitral/tufted cells to PC neurons was self-organized from a mutual
      information measure and by using a competitive Hebbian-Bayesian learning
      algorithm based on the response patterns of mitral/tufted cells to different
      odors yielding a distributed feed-forward projection to the PC. The PC was
      implemented as a modular attractor network with a recurrent connectivity that was
      likewise organized through Hebbian-Bayesian learning. We demonstrate the
      functionality of the model in a one-sniff-learning and recognition task on a set
      of 50 odorants. Furthermore, we study its robustness against noise on the
      receptor level and its ability to perform concentration invariant odor
      recognition. Moreover, we investigate the pattern completion capabilities of the
      system and rivalry dynamics for odor mixtures. 

PMID- 24570659
TI  - Preliminary evidence for performance enhancement following parietal lobe
      stimulation in Developmental Dyscalculia.
AB  - Nearly 7% of the population exhibit difficulties in dealing with numbers and
      performing arithmetic, a condition named Developmental Dyscalculia (DD), which
      significantly affects the educational and professional outcomes of these
      individuals, as it often persists into adulthood. Research has mainly focused on
      behavioral rehabilitation, while little is known about performance changes and
      neuroplasticity induced by the concurrent application of brain-behavioral
      approaches. It has been shown that numerical proficiency can be enhanced by
      applying a small-yet constant-current through the brain, a non-invasive technique
      named transcranial electrical stimulation (tES). Here we combined a numerical
      learning paradigm with transcranial direct current stimulation (tDCS) in two
      adults with DD to assess the potential benefits of this methodology to remediate
      their numerical difficulties. Subjects learned to associate artificial symbols to
      numerical quantities within the context of a trial and error paradigm, while tDCS
      was applied to the posterior parietal cortex (PPC). The first subject (DD1)
      received anodal stimulation to the right PPC and cathodal stimulation to the left
      PPC, which has been associated with numerical performance's improvements in
      healthy subjects. The second subject (DD2) received anodal stimulation to the
      left PPC and cathodal stimulation to the right PPC, which has been shown to
      impair numerical performance in healthy subjects. We examined two indices of
      numerical proficiency: (i) automaticity of number processing; and (ii) mapping of
      numbers onto space. Our results are opposite to previous findings with non
      dyscalculic subjects. Only anodal stimulation to the left PPC improved both
      indices of numerical proficiency. These initial results represent an important
      step to inform the rehabilitation of developmental learning disabilities, and
      have relevant applications for basic and applied research in cognitive
      neuroscience, rehabilitation, and education. 

PMID- 24570658
TI  - The development of vestibular system and related functions in mammals: impact of
      gravity.
AB  - This chapter reviews the knowledge about the adaptation to Earth gravity during
      the development of mammals. The impact of early exposure to altered gravity is
      evaluated at the level of the functions related to the vestibular system,
      including postural control, homeostatic regulation, and spatial memory. The
      hypothesis of critical periods in the adaptation to gravity is discussed.
      Demonstrating a critical period requires removing the gravity stimulus during
      delimited time windows, what is impossible to do on Earth surface. The surgical
      destruction of the vestibular apparatus, and the use of mice strains with
      defective graviceptors have provided useful information on the consequences of
      missing gravity perception, and the possible compensatory mechanisms, but
      transitory suppression of the stimulus can only be operated during spatial
      flight. The rare studies on rat pups housed on board of space shuttle
      significantly contributed to this problem, but the use of hypergravity
      environment, produced by means of chronic centrifugation, is the only available
      tool when repeated experiments must be carried out on Earth. Even though
      hypergravity is sometimes considered as a mirror situation to microgravity, the
      two situations cannot be confused because a gravitational force is still present.
      The theoretical considerations that validate the paradigm of hypergravity to
      evaluate critical periods are discussed. The question of adaption of graviceptor
      is questioned from an evolutionary point of view. It is possible that
      graviception is hardwired, because life on Earth has evolved under the constant
      pressure of gravity. The rapid acquisition of motor programming by precocial
      mammals in minutes after birth is consistent with this hypothesis, but the slow
      development of motor skills in altricial species and the plasticity of vestibular
      perception in adults suggest that gravity experience is required for the tuning
      of graviceptors. The possible reasons for this dichotomy are discussed. 

PMID- 24570660
TI  - The cortical activation pattern by a rehabilitation robotic hand: a functional
      NIRS study.
AB  - INTRODUCTION: Clarification of the relationship between external stimuli and
      brain response has been an important topic in neuroscience and brain
      rehabilitation. In the current study, using functional near infrared spectroscopy
      (fNIRS), we attempted to investigate cortical activation patterns generated
      during execution of a rehabilitation robotic hand. METHODS: Ten normal subjects
      were recruited for this study. Passive movements of the right fingers were
      performed using a rehabilitation robotic hand at a frequency of 0.5 Hz. We
      measured values of oxy-hemoglobin (HbO), deoxy-hemoglobin (HbR) and total
      hemoglobin (HbT) in five regions of interest: the primary sensory-motor cortex
      (SM1), hand somatotopy of the contralateral SM1, supplementary motor area (SMA),
      premotor cortex (PMC), and prefrontal cortex (PFC). RESULTS: HbO and HbT values
      indicated significant activation in the left SM1, left SMA, left PMC, and left
      PFC during execution of the rehabilitation robotic hand (uncorrected, p < 0.01).
      By contrast, HbR value indicated significant activation only in the hand
      somatotopic area of the left SM1 (uncorrected, p < 0.01). CONCLUSIONS: Our
      results appear to indicate that execution of the rehabilitation robotic hand
      could induce cortical activation.

PMID- 24570661
TI  - Influence of extracellular oscillations on neural communication: a computational
      perspective.
AB  - Neural communication generates oscillations of electric potential in the
      extracellular medium. In feedback, these oscillations affect the electrochemical
      processes within the neurons, influencing the timing and the number of action
      potentials. It is unclear whether this influence should be considered only as
      noise or it has some functional role in neural communication. Through computer
      simulations we investigated the effect of various sinusoidal extracellular
      oscillations on the timing and number of action potentials. Each simulation is
      based on a multicompartment model of a single neuron, which is stimulated through
      spatially distributed synaptic activations. A thorough analysis is conducted on a
      large number of simulations with different models of CA3 and CA1 pyramidal
      neurons which are modeled using realistic morphologies and active ion
      conductances. We demonstrated that the influence of the weak extracellular
      oscillations, which are commonly present in the brain, is rather stochastic and
      modest. We found that the stronger fields, which are spontaneously present in the
      brain only in some particular cases (e.g., during seizures) or that can be
      induced externally, could significantly modulate spike timings. 

PMID- 24570662
TI  - Retinoic acid modulates intrahippocampal levels of corticosterone in middle-aged
      mice: consequences on hippocampal plasticity and contextual memory.
AB  - It is now established that vitamin A and its derivatives, retinoic acid (RA), are
      required for cognitive functions in adulthood. RA hyposignaling and hyperactivity
      of glucocorticoid (GC) pathway appear concomitantly during aging and would
      contribute to the deterioration of hippocampal synaptic plasticity and functions.
      Furthermore, recent data have evidenced counteracting effects of retinoids on GC
      signaling pathway. In the present study, we addressed the following issue:
      whether the stimulation of RA pathway could modulate intrahippocampal
      corticosterone (CORT) levels in middle-aged mice and thereby impact on
      hippocampal plasticity and cognitive functions. We firstly investigated the
      effects of vitamin A supplementation and RA treatment in middle-aged mice, on
      contextual serial discrimination task, a paradigm which allows the detection of
      early signs of age-related hippocampal-dependent memory dysfunction. We then
      measured intrahippocampal CORT concentrations by microdialysis before and after a
      novelty-induced stress. Our results show that both RA treatment and vitamin A
      supplementation improve "episodic-like" memory in middle-aged mice but RA
      treatment appears to be more efficient. Moreover, we show that the beneficial
      effect of RA on memory is associated to an increase in hippocampal PSD-95
      expression. In addition, intrahippocampal CORT levels are reduced after novelty
      induced stress in RA-treated animals. This effect cannot be related to a
      modulation of hippocampal 11beta-HSD1 expression. Interestingly, RA treatment
      induces a modulation of RA receptors RARalpha and RARbeta expression in middle
      aged mice, a finding which has been correlated with the amplitude of
      intrahippocampal CORT levels after novelty-induced stress. Taken together, our
      results suggest that the preventive action of RA treatment on age-related memory
      deficits in middle-aged mice could be, at least in part, due to an inhibitory
      effect of retinoids on GC activity. 

PMID- 24570663
TI  - Latent classes of substance use in adolescent cannabis users: predictors and
      subsequent substance-related harm.
AB  - Cannabis use is highly prevalent in late adolescence, but not all users
      experience significant negative consequences. Little information is available to
      identify the substance use patterns and risk factors of users who are at greater
      risk of experiencing negative consequences. In this prospective study, we aimed
      to empirically identify latent classes of substance use in adolescent cannabis
      users and to examine how these classes relate to antecedent psychosocial
      predictors and subsequent substance-related outcomes. The sample was recruited
      from 68 high schools in Quebec and consisted of 1618 participants who reported
      using cannabis in grade 10. We used latent class analysis to empirically identify
      classes of users based on the age of onset, frequency, and typical quantity of
      cannabis and other substance use, as well as substance mixing behaviors. We then
      compared classes in terms of (a) sociodemographic and psychosocial predictors in
      grades 7-8 and (b) substance-related consequences in grade 11. Four distinct
      classes were identified: Late-Light Users (28%); Late-Heavy + Polydrug Users
      (14%); Early-Moderate Users (33%); Early-Heavy + Polydrug Users (26%). Late-Light
      Users reported the lowest levels of substance use, while Early-Heavy + Polydrug
      Users reported the highest levels. Intermediate levels of substance use were
      found in the other two classes. Sex, age, delinquency, peer delinquency, school
      bonding, parental monitoring, and parental conflict all helped to differentiate
      classes. Class membership predicted substance-related harm, with greater
      consequences in early- and late-onset heavy using classes. In light of results,
      in addition to age and sex, screening and intervention for risky cannabis use
      among adolescents should focus on school bonding in order to target the most
      risky late-onset adolescents and on peer delinquency in order to target the most
      risky early-onset ones. 

PMID- 24570665
TI  - The influence of prior practice and handedness on the orthogonal Simon effect.
AB  - When stimuli are arranged vertically and responses horizontally, right-handed
      participants respond faster with right responses to stimuli presented above
      fixation and with left responses to stimuli presented below fixation, even when
      stimulus position is task-irrelevant (orthogonal Simon effect). The aim of the
      present work was twofold. First, we assessed whether the orthogonal Simon effect
      evident in right-handed participants is present also for left-handed participants
      (Experiment 1). Second, we investigated whether for both groups of participants
      the orthogonal Simon effect is influenced by the stimulus-response (S-R) mapping
      used for an orthogonal spatial S-R compatibility task performed 5 min before
      (Experiment 2). Our results showed that the orthogonal Simon effect significantly
      differed in the two groups, with left-handers showing an advantage for the up
      left/down-right mapping (Experiment 1). Interestingly, the orthogonal Simon
      effect was strongly influenced by prior practice regardless of the participants'
      handedness (Experiment 2). These results suggest that the short-term S-R
      associations acquired during practice can override the long-term, hardwired
      associations established on the basis of handedness. 

PMID- 24570656
TI  - Impaired activity-dependent neural circuit assembly and refinement in autism
      spectrum disorder genetic models.
AB  - Early-use activity during circuit-specific critical periods refines brain
      circuitry by the coupled processes of eliminating inappropriate synapses and
      strengthening maintained synapses. We theorize these activity-dependent (A-D)
      developmental processes are specifically impaired in autism spectrum disorders
      (ASDs). ASD genetic models in both mouse and Drosophila have pioneered our
      insights into normal A-D neural circuit assembly and consolidation, and how these
      developmental mechanisms go awry in specific genetic conditions. The monogenic
      fragile X syndrome (FXS), a common cause of heritable ASD and intellectual
      disability, has been particularly well linked to defects in A-D critical period
      processes. The fragile X mental retardation protein (FMRP) is positively activity
      regulated in expression and function, in turn regulates excitability and activity
      in a negative feedback loop, and appears to be required for the A-D remodeling of
      synaptic connectivity during early-use critical periods. The Drosophila FXS model
      has been shown to functionally conserve the roles of human FMRP in
      synaptogenesis, and has been centrally important in generating our current
      mechanistic understanding of the FXS disease state. Recent advances in Drosophila
      optogenetics, transgenic calcium reporters, highly-targeted transgenic drivers
      for individually-identified neurons, and a vastly improved connectome of the
      brain are now being combined to provide unparalleled opportunities to both
      manipulate and monitor A-D processes during critical period brain development in
      defined neural circuits. The field is now poised to exploit this new Drosophila
      transgenic toolbox for the systematic dissection of A-D mechanisms in normal
      versus ASD brain development, particularly utilizing the well-established
      Drosophila FXS disease model. 

PMID- 24570667
TI  - Mental disorders are somatic disorders, a comment on M. Stier and T. Schramme.

PMID- 24570666
TI  - Sadness might isolate you in a non-smelling world: olfactory perception and
      depression.
AB  - Major depressive disorder (MDD) occurs with a high prevalence among mental
      illnesses. MDD patients experience sadness and hopelessness, with blunted
      affective reactivity. However, such depressive episodes are also key symptoms in
      other depressive disorders, like Bipolar Disorder (BPD) or Seasonal Affective
      Disorder (SAD). Moreover, depressive symptoms can also be found in healthy
      individuals, but are experienced as less severe or for a shorter duration than in
      patients. Here, it is aimed to summarize studies investigating odor perception in
      depression, including depressive states in healthy individuals and patient
      populations. Odor perception in depression has been assessed with psychophysical
      methods (olfactory sensitivity, odor identification, and discrimination), and
      odor ratings (intensity, emotional valence, familiarity). In addition, some
      studies investigated affective reactions to odors, and physiological and
      anatomical correlates of odor perception in depression. The summary reveals that
      MDD is associated with reduced olfactory sensitivity. However, odor
      identification and discrimination scores seem to be unaffected by depression. The
      reduced olfactory sensitivity might be associated with a reduced ability to
      encode olfactory information and a reduced volume of the olfactory bulb. While
      similar processes seem to occur in healthy individuals experiencing depressive
      states, they have not been observed in BPD or SAD patients. However, in order to
      conclude that the reduced olfactory sensitivity is directly linked to depression,
      it is suggested that studies should implement control measures of cognitive
      performances or perceptual abilities in other stimulus modalities. It is
      concluded that the reduced olfactory performance in MDD patients seems to be
      disorder-, modality-, and test-specific, and that the application of an
      appropriate olfactory and cognitive test-battery might be highly useful in the
      differential diagnosis of MDD. 

PMID- 24570664
TI  - The influences of age on olfaction: a review.
AB  - Decreased olfactory function is very common in the older population, being
      present in over half of those between the ages of 65 and 80 years and in over
      three quarters of those over the age of 80 years. Such dysfunction significantly
      influences physical well-being and quality of life, nutrition, the enjoyment of
      food, as well as everyday safety. Indeed a disproportionate number of the elderly
      die in accident gas poisonings each year. As described in this review, multiple
      factors contribute to such age-related loss, including altered nasal engorgement,
      increased propensity for nasal disease, cumulative damage to the olfactory
      epithelium from viral and other environmental insults, decrements in mucosal
      metabolizing enzymes, ossification of cribriform plate foramina, loss of
      selectivity of receptor cells to odorants, changes in neurotransmitter and
      neuromodulator systems, and neuronal expression of aberrant proteins associated
      with neurodegenerative disease. It is now well established that decreased smell
      loss can be an early sign of such neurodegenerative diseases as Alzheimer's
      disease and sporadic Parkinson's disease. In this review we provide an overview
      of the anatomy and physiology of the aging olfactory system, how this system is
      clinically evaluated, and the multiple pathophysiological factors that are
      associated with its dysfunction. 

PMID- 24570670
TI  - Once upon a time, there was a fabulous funambulist...: what children learn about
      the "high-level" vocabulary they encounter while listening to stories.
AB  - Previous research has shown that listening to stories supports vocabulary growth
      in preschool and school-aged children and that lexical entries for even very
      difficult or rare words can be established if these are defined when they are
      first introduced. However, little is known about the nature of the lexical
      representations children form for the words they encounter while listening to
      stories, or whether these are sufficiently robust to support the child's own use
      of such "high-level" vocabulary. This study explored these questions by
      administering multiple assessments of children's knowledge about a set of newly
      acquired vocabulary. Four- and six-year-old children were introduced to nine
      difficult new words (including nouns, verbs and adjectives) through three
      exposures to a story read by their class teacher. The story included a definition
      of each new word at its first encounter. Learning of the target vocabulary was
      assessed by means of two tests of semantic understanding-a forced choice picture
      selection task and a definition production task-and a grammaticality judgment
      task, which asked children to choose between a syntactically-appropriate and
      syntactically-inappropriate usage of the word. Children in both age groups
      selected the correct pictorial representation and provided an appropriate
      definition for the target words in all three word classes significantly more
      often than they did for a matched set of non-exposed control words. However, only
      the older group was able to identify the syntactically-appropriate sentence
      frames in the grammaticality judgment task. Further analyses elucidate some of
      the components of the lexical representations children lay down when they hear
      difficult new vocabulary in stories and how different tests of word knowledge
      might overlap in their assessment of these components. 

PMID- 24570668
TI  - Lifespan development of attentiveness in domestic dogs: drawing parallels with
      humans.
AB  - Attention is pivotal to consciousness, perception, cognition, and working memory
      in all mammals, and therefore changes in attention over the lifespan are likely
      to influence development and aging of all of these functions. Due to their
      evolutionary and developmental history, the dog is being recognized as an
      important species for modeling human healthspan, aging and associated diseases.
      In this study, we investigated the normal lifespan development of attentiveness
      of pet dogs in naturalistic situations, and compared the resulting cross
      sectional developmental trajectories with data from previous studies in humans.
      We tested a sample of 145 Border collies (6 months to 14 years) with humans and
      objects or food as attention attractors, in order to assess their attentional
      capture, sustained and selective attention, and sensorimotor abilities. Our
      results reveal differences in task relevance in sustained attentional performance
      when watching a human or a moving object, which may be explained by life-long
      learning processes involving such stimuli. During task switching we found that
      dogs' selective attention and sensorimotor abilities showed differences between
      age groups, with performance peaking at middle age. Dogs' sensorimotor abilities
      showed a quadratic distribution with age and were correlated with selective
      attention performance. Our results support the hypothesis that the development
      and senescence of sensorimotor and attentional control may be fundamentally
      interrelated. Additionally, attentional capture, sustained attention, and
      sensorimotor control developmental trajectories paralleled those found in humans.
      Given that the development of attention is similar across humans and dogs, we
      propose that the same regulatory mechanisms are likely to be present in both
      species. Finally, this cross-sectional study provides the first description of
      age group changes in attention over the lifespan of pet dogs. 

PMID- 24570669
TI  - Visual cortex in aging and Alzheimer's disease: changes in visual field maps and
      population receptive fields.
AB  - Although several studies have suggested that cortical alterations underlie such
      age-related visual deficits as decreased acuity, little is known about what
      changes actually occur in visual cortex during healthy aging. Two recent studies
      showed changes in primary visual cortex (V1) during normal aging; however, no
      studies have characterized the effects of aging on visual cortex beyond V1,
      important measurements both for understanding the aging process and for
      comparison to changes in age-related diseases. Similarly, there is almost no
      information about changes in visual cortex in Alzheimer's disease (AD), the most
      common form of dementia. Because visual deficits are often reported as one of the
      first symptoms of AD, measurements of such changes in the visual cortex of AD
      patients might improve our understanding of how the visual system is affected by
      neurodegeneration as well as aid early detection, accurate diagnosis and timely
      treatment of AD. Here we use fMRI to first compare the visual field map (VFM)
      organization and population receptive fields (pRFs) between young adults and
      healthy aging subjects for occipital VFMs V1, V2, V3, and hV4. Healthy aging
      subjects do not show major VFM organizational deficits, but do have reduced
      surface area and increased pRF sizes in the foveal representations of V1, V2, and
      hV4 relative to healthy young control subjects. These measurements are consistent
      with behavioral deficits seen in healthy aging. We then demonstrate the
      feasibility and first characterization of these measurements in two patients with
      mild AD, which reveal potential changes in visual cortex as part of the
      pathophysiology of AD. Our data aid in our understanding of the changes in the
      visual processing pathways in normal aging and provide the foundation for future
      research into earlier and more definitive detection of AD. 

PMID- 24570671
TI  - The role of emotional engagement and mood valence in retrieval fluency of mood
      incongruent autobiographical memory.
AB  - BACKGROUND: Retrieval of opposite mood autobiographical memories serves emotion
      regulation, yet the factors influencing this ability are poorly understood.
      METHODS: Three studies examined the effect of mood valence (sad vs. happy) and
      degree of emotional engagement on fluency of mood incongruent retrieval by
      manipulating emotional engagement and examining the effect of emotional film
      clips on the Fluency of Autobiographical Memory task. RESULTS: Following both sad
      and happy film clips, participants who received emotionally engaging instructions
      exhibited a greater recall latency of the first opposite mood memory, and had
      generated less such memories than those receiving emotionally disengaging
      instructions (Studies 1 and 2). A happy mood induction resulted in recollection
      of fewer mood incongruent memories compared to a sad mood induction. Providing
      emotionally engaging instructions was found to specifically hinder mood
      incongruent retrieval, without impairing mood congruent retrieval (Study 3).
      CONCLUSION: High emotional engagement seems to impair the retrieval of mood
      incongruent memories. Being in a happy mood may also partially impair such
      retrieval. Implications regarding emotional regulation are discussed.

PMID- 24570673
TI  - Action game experimental evidence for effects on aggression and visuospatial
      cognition: similarities, differences, and one rather foolish question.

PMID- 24570672
TI  - Age differences in medial prefrontal activity for subsequent memory of truth
      value.
AB  - Much research has demonstrated that aging is marked by decreased source memory
      relative to young adults, yet a smaller body of work has demonstrated that
      increasing the socioemotional content of source information may be one way to
      reduce age-related performance differences. Although dorsomedial prefrontal
      cortex (dmPFC) activity may support source memory among young and older adults,
      the extent to which one activates dorsal vs. ventral mPFC may reflect one's
      personal connection with incoming information. Because truth value may be one
      salient marker that impacts one's connection with information and allocation of
      attention toward incoming material, we investigated whether the perceived truth
      value of information differently impacts differences in mPFC activity associated
      with encoding source information, particularly with age. Twelve young (18-23
      years) and 12 older adults (63-80 years) encoded true and false statements.
      Behavioral results showed similar memory performance between the age groups. With
      respect to neural activity associated with subsequent memory, young adults,
      relative to older adults, exhibited greater activity in dmPFC while older adults
      displayed enhanced ventromedial prefrontal cortex (vmPFC) and insula engagement
      relative to young. These results may potentially indicate that young adults focus
      on a general knowledge acquisition goal, while older adults focus on emotionally
      relevant aspects of the material. The findings demonstrate that age-related
      differences in recruitment of mPFC associated with encoding source information
      may in some circumstances underlie age-equivalent behavioral performance. 

PMID- 24570674
TI  - Somatostatin analogs therapy in gastroenteropancreatic neuroendocrine tumors:
      current aspects and new perspectives.
AB  - Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare tumors that
      present many clinical features secreting peptides and neuroamines that cause
      distinct clinical syndromes such as carcinoid syndrome. However most of them are
      clinically silent until late presentation with mass effects. Surgical resection
      is the first line treatment for a patient with a GEP-NET while in metastatic
      disease multiple therapeutic approaches are possible. GEP-NETs are able to
      express somatostatin receptors (SSTRs) bounded by somatostatin (SST) or its
      synthetic analogs, although the subtypes and number of SSTRs expressed are very
      variable. In particular, SST analogs are used frequently to control hormone
      related symptoms while their anti-neoplastic activity seems to result prevalently
      in tumor stabilization. Patients who fail to respond or cease to respond to
      standard SST analogs treatment seem to have a response to higher doses of these
      drugs. For this reason, the use of higher doses of SST analogs will probably
      improve the clinical management of these patients. 

PMID- 24570675
TI  - Evolution of microbiological analytical methods for dairy industry needs.
AB  - Traditionally, culture-based methods have been used to enumerate microbial
      populations in dairy products. Recent developments in molecular methods now
      enable faster and more sensitive analyses than classical microbiology procedures.
      These molecular tools allow a detailed characterization of cell physiological
      states and bacterial fitness and thus, offer new perspectives to integration of
      microbial physiology monitoring to improve industrial processes. This review
      summarizes the methods described to enumerate and characterize physiological
      states of technological microbiota in dairy products, and discusses the current
      deficiencies in relation to the industry's needs. Recent studies show that
      Polymerase chain reaction-based methods can successfully be applied to quantify
      fermenting microbes and probiotics in dairy products. Flow cytometry and omics
      technologies also show interesting analytical potentialities. However, they still
      suffer from a lack of validation and standardization for quality control
      analyses, as reflected by the absence of performance studies and official
      international standards. 

PMID- 24570676
TI  - Pre-Clinical Assessment of Immune Responses to Adeno-Associated Virus (AAV)
      Vectors.
AB  - Transitioning to human trials from pre-clinical models resulted in the emergence
      of inhibitory AAV vector immune responses which has become a hurdle for sustained
      correction. Early animal studies did not predict the full range of host immunity
      to the AAV vector in human studies. While pre-existing antibody titers against
      AAV vectors has been a lingering concern, cytotoxic T-cell (CTL) responses
      against the input capsid can prevent long-term therapy in humans. These
      discoveries spawned more thorough profiling of immune response to rAAV in pre
      clinical models, which have assessed both innate and adaptive immunity and
      explored methods for bypassing these responses. Many efforts toward measuring
      innate immunity have utilized Toll-like receptor deficient models and have
      focused on differential responses to viral capsid and genome. From adaptive
      studies, it is clear that humoral responses are relevant for initial vector
      transduction efficiency while cellular responses impact long-term outcomes of
      gene transfer. Measuring humoral responses to AAV vectors has utilized in vitro
      neutralizing antibody assays and transfer of seropositive serum to
      immunodeficient mice. Overcoming antibodies using CD20 inhibitors,
      plasmapheresis, altering route of delivery and using different capsids have been
      explored. CTL responses were measured using in vitro and in vivo models. In in
      vitro assays expansion of antigen-specific T-cells as well as cytotoxicity toward
      AAV transduced cells can be shown. Many groups have successfully mimicked antigen
      specific T-cell proliferation, but actual transgene level reduction and
      parameters of cytotoxicity toward transduced target cells have only been shown in
      one model. The model utilized adoptive transfer of capsid-specific in vitro
      expanded T-cells isolated from immunized mice with LPS as an adjuvant. Finally,
      the development of immune tolerance to AAV vectors by enriching regulatory T
      cells as well as modulating the response pharmacologically has also been
      explored. 

PMID- 24570677
TI  - Large-scale analysis of B-cell epitopes on influenza virus hemagglutinin -
      implications for cross-reactivity of neutralizing antibodies.
AB  - Influenza viruses continue to cause substantial morbidity and mortality
      worldwide. Fast gene mutation on surface proteins of influenza virus result in
      increasing resistance to current vaccines and available antiviral drugs. Broadly
      neutralizing antibodies (bnAbs) represent targets for prophylactic and
      therapeutic treatments of influenza. We performed a systematic bioinformatics
      study of cross-reactivity of neutralizing antibodies (nAbs) against influenza
      virus surface glycoprotein hemagglutinin (HA). This study utilized the available
      crystal structures of HA complexed with the antibodies for the analysis of tens
      of thousands of HA sequences. The detailed description of B-cell epitopes,
      measurement of epitope area similarity among different strains, and estimation of
      antibody neutralizing coverage provide insights into cross-reactivity status of
      existing nAbs against influenza virus. We have developed a method to assess the
      likely cross-reactivity potential of bnAbs for influenza strains, either newly
      emerged or existing. Our method catalogs influenza strains by a new concept named
      discontinuous peptide, and then provide assessment of cross-reactivity.
      Potentially cross-reactive strains are those that share 100% identity with
      experimentally verified neutralized strains. By cataloging influenza strains and
      their B-cell epitopes for known bnAbs, our method provides guidance for selection
      of representative strains for further experimental design. The knowledge of
      sequences, their B-cell epitopes, and differences between historical influenza
      strains, we enhance our preparedness and the ability to respond to the emerging
      pandemic threats. 

PMID- 24570678
TI  - Systems analysis of transcriptome data provides new hypotheses about Arabidopsis
      root response to nitrate treatments.
AB  - Nitrogen (N) is an essential macronutrient for plant growth and development.
      Plants adapt to changes in N availability partly by changes in global gene
      expression. We integrated publicly available root microarray data under
      contrasting nitrate conditions to identify new genes and functions important for
      adaptive nitrate responses in Arabidopsis thaliana roots. Overall, more than 2000
      genes exhibited changes in expression in response to nitrate treatments in
      Arabidopsis thaliana root organs. Global regulation of gene expression by nitrate
      depends largely on the experimental context. However, despite significant
      differences from experiment to experiment in the identity of regulated genes,
      there is a robust nitrate response of specific biological functions. Integrative
      gene network analysis uncovered relationships between nitrate-responsive genes
      and 11 highly co-expressed gene clusters (modules). Four of these gene network
      modules have robust nitrate responsive functions such as transport, signaling,
      and metabolism. Network analysis hypothesized G2-like transcription factors are
      key regulatory factors controlling transport and signaling functions. Our meta
      analysis highlights the role of biological processes not studied before in the
      context of the nitrate response such as root hair development and provides
      testable hypothesis to advance our understanding of nitrate responses in plants. 

PMID- 24570679
TI  - Molybdenum metabolism in plants and crosstalk to iron.
AB  - In the form of molybdate the transition metal molybdenum is essential for plants
      as it is required by a number of enzymes that catalyze key reactions in nitrogen
      assimilation, purine degradation, phytohormone synthesis, and sulfite
      detoxification. However, molybdate itself is biologically inactive and needs to
      be complexed by a specific organic pterin in order to serve as a permanently
      bound prosthetic group, the molybdenum cofactor, for the socalled molybdo
      enyzmes. While the synthesis of molybdenum cofactor has been intensively studied,
      only little is known about the uptake of molybdate by the roots, its transport to
      the shoot and its allocation and storage within the cell. Yet, recent evidence
      indicates that intracellular molybdate levels are tightly controlled by molybdate
      transporters, in particular during plant development. Moreover, a tight
      connection between molybdenum and iron metabolisms is presumed because (i) uptake
      mechanisms for molybdate and iron affect each other, (ii) most molybdo-enzymes do
      also require iron-containing redox groups such as iron-sulfur clusters or heme,
      (iii) molybdenum metabolism has recruited mechanisms typical for iron-sulfur
      cluster synthesis, and (iv) both molybdenum cofactor synthesis and
      extramitochondrial iron-sulfur proteins involve the function of a specific
      mitochondrial ABC-type transporter. 

PMID- 24570680
TI  - GIP/MZT1 proteins orchestrate nuclear shaping.
AB  - The functional organization of the nuclear envelope (NE) is only just emerging in
      plants with the recent characterization of NE protein complexes and their
      molecular links to the actin cytoskeleton. The NE also plays a role in
      microtubule nucleation by recruiting gamma-Tubulin Complexes (gamma-TuCs) which
      contribute to the establishment of a robust mitotic spindle. gamma-tubulin
      Complex Protein 3 (GCP3)-interacting proteins (GIPs) have been identified
      recently as integral components of gamma-TuCs. GIPs have been conserved
      throughout evolution and are also named MZT1 (mitotic-spindle organizing protein
      1). This review focuses on recent data investigating the role of GIP/MZT1 at the
      NE, including insights from the study of GIP partners. It also uncovers new
      functions for GIP/MZT1 during interphase and highlights a current view of NE
      associated components which are critical for nuclear shaping during both cell
      division and differentiation. 

PMID- 24570681
TI  - Trends of the Incidence of Ischemic Stroke Thrombolysis over Seven Years and One
      Year Outcome: A Population-Based Study in Joinville, Brazil.
AB  - BACKGROUND: In a population-based setting, we aimed to measure the incidence
      trends of ischemic stroke (IS) thrombolysis, thrombolysis times, proportion of
      symptomatic intracerebral hemorrhage (sICH), 30-day case fatality and functional
      outcomes. We also compared the 12-month functional status between thrombolyzed
      and nonthrombolyzed patients. METHODS: Using data from the Joinville Population
      Based Stroke Registry, we prospectively ascertained a cohort of all thrombolyses
      done in Joinville citizens, Southern Brazil, from 2005 to 2011. For the
      definition of sICH we used European Cooperative Acute Stroke Study (ECASS) II
      criteria. RESULTS: Over 7 years, 6% (220/3,552) of all IS were thrombolyzed. The
      thrombolysis incidence increased from 1.4 [95% confidence interval (CI), 0.6-2.9]
      in 2005 to 9.8 (7.3-12.9) per 100,000 population in 2011 (p < 0.0001). The
      thrombolysis incidence age-adjusted to the world population in 2011 was 11 (8.2
      14.3) per 100,000. Only 30% (50/165) were thrombolyzed within 1 h of arrival at
      hospital. In 7 days, 6.4% (14/220) had sICH and 57% (8/14) of those died. In the
      2009-2011 period, a favorable functional outcome [modified Rankin scale (mRS) 0
      1] at 12 months among patients who received thrombolysis was more frequent [mRS 0
      1; 36% (38/107)] than among patients who did not receive thrombolysis [mRS 0-1;
      24% (131/544); p = 0.016]. The logistic regression showed that thrombolyzed IS
      patients had a more favorable outcome (mRS 0-1; HR 2.13; 95% CI, 1.2-3.7; p <
      0.016) than nonthrombolyzed patients. CONCLUSION: In a population setting of a
      middle income country, the thrombolysis incidence and outcomes were similar to
      those of other well-structured services. After 1 year, patients thrombolyzed in
      the 4.5-hour time window had a better outcome. More than proportions, rates
      provide additional information and could be used to benchmark services against
      others.

PMID- 24570682
TI  - Glomerulopathy with homozygous apolipoprotein e2: a report of three cases and
      review of the literature.
AB  - Most cases of type III hyperlipoproteinemia are accounted for by apolipoprotein
      E2 (apoE2) homozygotes, a genetic mutation of apoE (Arg158Cys). Glomerulopathy
      with homozygous apoE2 is rare and characterized by marked foam cell infiltration
      in the glomerular capillaries and mesangium. Here, we report 3 cases of apoE2
      homozygote glomerulopathy diagnosed by renal biopsy and DNA analysis. All 3 cases
      were middle-aged or elderly males complicated with diabetes for at least a
      decade. The kidney biopsies showed massive foam cell infiltration in the
      glomerular capillaries and expanded mesangium accompanied by histological
      findings of diabetic glomerulosclerosis. The lipid profiles showed type III
      hyperlipoproteinemia and phenotypic/genetic analyses revealed homozygosity of
      apoE2. Two of the cases showed nephrotic proteinuria and progressed to renal
      failure in 3 and 8 years after the diagnosis of kidney disease. 

PMID- 24570683
TI  - An unusual prostate-specific antigen decrease in an advanced castration-resistant
      prostate cancer patient with intracerebral hemorrhage subsequently treated with
      luteinizing hormone-releasing hormone antagonist.
AB  - An unusual prostate-specific antigen (PSA) decrease in a Japanese patient with
      advanced castration-resistant prostate cancer (CRPC) treated with luteinizing
      hormone-releasing hormone (LH-RH) antagonist after cerebral bleeding was
      presented. There have been no previous reports that cerebral bleeding or
      trepanation/drainage of hematoma decreased PSA level, which would make this the
      first. The LH-RH antagonist may be only one reason for the PSA decrease. More
      cases need to be accumulated and and further investigation is needed to clarify
      if intracerebral bleeding or an LH-RH antagonist can decrease PSA in such
      advanced CRPC cases. 

PMID- 24570684
TI  - A case of atypical hemolytic uremic syndrome successfully treated with
      eculizumab.
AB  - Atypical hemolytic uremic syndrome (aHUS) is a rare thrombotic microangiopathy
      (TMA) characterized by the triad of hemolytic anemia, thrombocytopenia, and acute
      renal failure. Eculizumab, a monoclonal complement C5 antibody which prevents the
      induction of the terminal complement cascade, has recently emerged as a
      therapeutic option for aHUS. We report a case of aHUS successfully treated with
      eculizumab. A 51-year-old male was admitted to the hospital following a
      mechanical fall. His past medical history was significant for rheumatic valve
      disease and mitral valve replacement; he was on warfarin for anticoagulation. A
      computed tomography scan of the head revealed a right-sided subdural hematoma due
      to coagulopathy resulting from a supratherapeutic international normalized ratio
      (INR). Following treatment with prothrombin complex concentrate to reverse the
      INR, urine output dropped and his serum creatinine subsequently increased to
      247.52 MUmol/l from the admission value of 70.72 MUmol/l. Laboratory evaluation
      was remarkable for hemolytic anemia, thrombocytopenia, elevated lactate
      dehydrogenase (LDH), low haptoglobin, and low complement C3. A renal biopsy was
      consistent with TMA, favoring a diagnosis of aHUS. Treatment with eculizumab was
      initiated which resulted in the stabilization of his hemoglobin, platelets, and
      LDH. Hemodialysis was terminated after 2.5 months due to improvement in urine
      output and solute clearance. The interaction between thrombin and complement
      pathway might be responsible for the pathogenesis of aHUS in this case.
      Eculizumab is an effective therapeutic agent in the treatment of aHUS. Early
      targeting of the complement system may modify disease progression and thus treat
      aHUS more effectively. 

PMID- 24570685
TI  - A case of water intoxication with prolonged hyponatremia caused by excessive
      water drinking and secondary SIADH.
AB  - Water intoxication is a life-threatening disorder accompanied by brain function
      impairment due to severe dilutional hyponatremia. We treated a 22-year-old man
      without psychotic illness who had been put in a detention facility. He drank 6
      liters of water over a 3-hour period at the facility as a game's penalty, and he
      showed progressive psychiatric and neurological signs including restlessness,
      peculiar behavior and convulsions. On his admission, 15 h after the
      discontinuation of the water drinking, he was in a coma, showing intermittent
      convulsions and remarkable hyponatremia (120 mmol/l). Because his laboratory
      tests showed hypertonic urine and normal sodium excretion, the diagnosis of
      secondary development of syndrome of inappropriate secretion of antidiuretic
      hormone (SIADH) was strongly suggested and later confirmed by the suppression of
      the renin-aldosterone system and the inappropriately elevated secretion of ADH.
      Saline infusion and an initial administration of furosemide in addition to
      dexamethasone as treatments for the patient's brain edema successfully improved
      his laboratory data and clinical signs by the 3rd hospital day, and he was
      returned to the facility without physical or psychiatric abnormalities on the 6th
      day. The secondary SIADH might have been due to the prolonged emesis, recurrent
      convulsions and rapid elevation of intracranial pressure. 

PMID- 24570686
TI  - Lumen and calcium characteristics within calcified coronary lesions. Comparison
      of computed tomography coronary angiography versus intravascular ultrasound.
AB  - INTRODUCTION: Computed tomography coronary angiography (CTCA) is a diagnostic
      method used for exclusion of coronary artery disease. However, lower accuracy of
      CTCA in assessment of calcified lesions is a significant factor impeding
      applicability of CTCA for assessment of coronary atherosclerosis. AIM: To provide
      insight into lumen and calcium characteristics assessed with CTCA, we compared
      these parameters to the reference of intravascular ultrasound (IVUS). MATERIAL
      AND METHODS: Two hundred and fifty-two calcified lesions within 97 arteries of 60
      patients (19 women, age 63 +/-10 years) underwent assessment with both 2 * 64
      slice CT (Somatom Definition, Siemens) and IVUS (s5, Volcano Corp.). Coronary
      lumen and calcium dimensions within calcified lesions were assessed with CTCA and
      compared to the reference measurements made with IVUS. RESULTS: On average CTCA
      underestimated mean lumen diameter (2.8 +/-0.7 mm vs. 2.9 +/-0.8 mm for IVUS),
      lumen area (6.4 +/-3.4 mm(2) vs. 7.0 +/-3.7 mm(2) for IVUS, p < 0.001) and total
      calcium arc (52 +/-35 degrees  vs. 83 +/-54 degrees ). However, analysis of
      tertiles of the examined parameters revealed that the mean lumen diameter, lumen
      area and calcium arc did not significantly differ between CTCA and IVUS within
      the smallest lumens (1(st) tertile of mean lumen diameter at 2.1 mm, and 1(st)
      tertile of lumen area at 3.7 mm(2)) and lowest calcium arc (mean of 40 degrees ).
      CONCLUSIONS: Although, on average, CTCA underestimates lumen diameter and area as
      well as calcium arc within calcified lesions, the differences are not significant
      within the smallest vessels and calcium arcs. The low diagnostic accuracy of CTCA
      within calcified lesions may be attributed to high variance and not to systematic
      error of measurements.

PMID- 24570687
TI  - What is the optimal cut-off point for low coronary artery calcium score assessed
      by computed tomography? Multi-Detector Computed Tomography ANIN Registry.
AB  - AIM: This prospective study was conducted to evaluate the incidence and
      predictors of coronary artery disease (CAD) in relation to the low coronary
      artery calcium (CAC) score among patients with intermediate probability of CAD.
      MATERIAL AND METHODS: A total of 1132 consecutive patients were included in the
      analysis (58.7 +/-10.9 years, 46.7% males). Coronary computed tomography (CCT)
      angiography was performed in a multi-detector computed tomography scanner.
      Coronary artery calcium score was calculated by the Agatston method. Obstructive
      CAD was defined as the presence of coronary artery stenosis >= 50% on CCT
      angiography. RESULTS: Coronary artery disease was diagnosed in nearly one-fourth
      of patients (n = 272, 24%). In the receiver operating characteristics (ROC) curve
      analysis a CAC score of 10 was used as an optimal cut-off point for
      discriminating obstructive CAD (sensitivity: 0.79, specificity: 0.75, p < 0.0001)
      whereas for a CAC score of 100 the sensitivity and specificity were 0.48 and
      0.92, respectively. On multivariate analysis after adjustment for age, gender,
      hypertension, hyperlipidemia, creatinine levels, only in patients with CAC score
      <= 10 age (OR = 1.05, 95% CI: 1.02-1.08, p = 0.0005, OR = 1.05, 95% CI: 1.03
      1.08, p < 0.0001) and male gender (OR = 3.45, 95% CI: 1.92-6.22, p < 0.0001),
      likewise in group with CAC score <= 100 age (OR = 1.05, 95% CI: 1.03-1.08, p <
      0.0001) and male gender (OR = 3.31, 95% CI: 1.88-5.81, p < 0.0001) were
      independent predictors of obstructive CAD. CONCLUSIONS: The cut-off point of 10
      for CAC score determined patients with CAD with the best sensitivity and
      specificity. Therefore, a total CAC score < 10 should be classified as "low". In
      patients with a low CAC score obstructive high risk plaques prone to rupture are
      presented and are associated with increasing age and male gender.

PMID- 24570688
TI  - Regaining venous access for implantation of a new lead.
AB  - INTRODUCTION: Venous occlusion is a relatively common complication of endocardial
      lead implantation. It may cause a critical problem when implantation of a new
      lead is needed. Traditional methods result in leaving abandoned leads. The
      optimal approach seems to be the extraction of the damaged or abandoned lead,
      regaining venous access and implantation of a new lead. AIM: To assess the
      efficacy and safety of new lead implantation by the method of lead extraction.
      MATERIAL AND METHODS: All transvenous lead extraction procedures (203 patients)
      between 1 August 2008 and 15 October 2012 were assessed. The analysis included
      cases with leads implanted for at least 6 months prior to extraction. RESULTS:
      Regaining venous access was the main indication for lead extraction in 5 patients
      (4.9%). The reason for new lead implantation was lead damage (n = 7) and system
      up-grade to cardiac resynchronization therapy (CRT) (n = 3). In total, 23 leads
      were extracted (9 defibrillation leads, 12 pacing leads and 2 left ventricular
      leads). The mean time from the implantation was 92.2 +/-43.2 (48-152) months. In
      all cases Cook mechanical sheaths were applied. The use of the Evolution system
      was necessary to extract 3 leads. In all cases the new leads were successfully
      implanted as planned. No serious complications occurred. CONCLUSIONS: Diagnosis
      of venous occlusion should not be a contraindication for ipsilateral implantation
      of the new lead, because the techniques of transvenous lead extraction enable
      successful regaining of venous access.

PMID- 24570689
TI  - Biodegradable vascular scaffold ABSORB BVSTM - scientific evidence and methods of
      implantation.
AB  - Since 2006, over 600 biodegradable vascular scaffolds (BVS) have been implanted
      worldwide in clinical trials such as ABSORB cohort A and B, ABSORB Extend and
      ABSORB II RCT. Due to completely changed construction and mechanical properties
      of BVS, the choice of proper scaffold diameter and its implantation differ
      significantly from those used in the case of metal stents (bare metal stent (BMS)
      or drug eluting stent (DES)). Furthermore, all data concerning BVS efficacy and
      safety come from clinical trials, conducted in a selected group of patients. In
      2012 BVS ABSORBTM was approved as the first biodegradable scaffold for the
      treatment of coronary artery disease in EU and other countries, with a limitation
      of use only for experienced and trained interventional cardiologists. As one of
      the most experienced clinical centers in Europe and the first one that in 2006
      implanted BVS ABSORBTM in Poland we have a great pleasure and honor to share our
      experience with interventional cardiologists who would like to prepare for BVS
      ABSORBTM implantation in their centers. In this article we wanted to summarize
      the clinical data from already finished and ongoing trials, give a short overview
      of patient selection, and provide a detailed description of the implantation
      process with tips which could be helpful during BVS use. 

PMID- 24570690
TI  - Is further improvement of the treatment of acute coronary syndromes still
      possible?
AB  - Successful treatment of myocardial infarction related to early reperfusion
      therapy has caused growing interest in not only ischemic but also myocardial
      reperfusion injury. Most experimentally confirmed preservation myocardial
      reperfusion injury methods have failed in clinical practice. Probably one reason
      for their ineffectiveness was the very narrow "time window" necessitating
      application of protective methods before obtaining reperfusion. Reducing the
      myocardial necrosis and preservation of the left ventricular function are the
      main goals of the therapy. Experimental data suggest that up to 50% of the
      infarct size may be related to reperfusion injury. Function of the mitochondrial
      permeability transition pore (mPTP) in the inner mitochondrial membrane, being
      closed during myocardial ischemia and opening at the beginning of reperfusion, is
      the common element linking protective methods. Their opening gives rise to
      metabolic alterations and may lead to cardiomyocyte death (lethal reperfusion
      injury). That is why successful intervention, very difficult to achieve, has to
      take precedence over coronary blood flow restoration. Cyclosporin A, an mPTP
      blocker, was effective in the first small clinical trial in preservation of
      myocardial reperfusion injury in acute coronary syndrome intervention. Second
      mitochondrial injury action is related to generation of reactive oxygen species
      (ROS) including superoxide anions. Reactive oxygen species accumulation results
      in mitochondrial pH increase leading to mPTP opening. Discovery of a small
      molecule cationic peptide, readily penetrating cell membranes and concentrating
      in mitochondria, may give new therapy perspectives. Combining therapy may be
      possible as well. 

PMID- 24570691
TI  - The use of drug-eluting stents in acute myocardial infarction - is the battle
      coming to an end? From despair to acceptance.
AB  - The large-scale use of drug-eluting stents (DES) in elective percutaneous
      coronary interventions resulted in a significant reduction of restenosis and the
      need for repeat revascularization, compared to bare-metal stents (BMS) and
      balloon angioplasty. The position of DES used during primary percutaneous
      coronary intervention was not so well established. Based on the trials including
      the general population of patients, an increased risk of stent thrombosis was
      indicated, particularly late after implantation, which may be associated with
      increased mortality. A number of randomized clinical trials have compared first
      generation DES with BMS in acute ST-segment elevation myocardial infarction
      (STEMI). In most of them increased mortality after DES implantation was not
      confirmed, with demonstrated reduction of repeat revascularizations. However,
      long-term follow-up of these studies and the results from non-randomized "real
      world" registries are equivocal. A new generation of DES has been present on the
      market for several years. They have modern designs, are covered with more neutral
      polymers and release new drugs. The new generation DES have a better safety and
      efficacy profile, including a population of patients with acute STEMI, than the
      first generation stents. This paper is a review of randomized controlled trials,
      meta-analyses and registries, comparing DES with BMS in patients with acute
      STEMI. Attention was drawn to the current position and the role of new generation
      DES, which may prove to be a safe and effective choice in this population of
      patients. 

PMID- 24570693
TI  - Stent implantation into intracranial part of internal carotid artery in a patient
      with recurrent stroke, atrial fibrillation and iatrogenic bleeding during
      anticoagulant therapy.
AB  - Cardiovascular diseases are the leading cause of stroke. We present a 45-year-old
      woman with left hemisphere stroke, in which two sources of cerebral embolism were
      detected: atrial fibrillation and stenosis of intracranial part of left internal
      carotid artery. Oral anticoagulant therapy was used. The patient was qualified
      for intracranial revascularization. During anticoagulant therapy iatrogenic
      bleeding and then left hemisphere stroke occurred. Ultimately, the stent was
      implanted into the intracranial part of the internal carotid artery. Due to
      atrial fibrillation the patient is qualified for percutaneous closure of the left
      atrial appendage. 

PMID- 24570694
TI  - Percutaneous angioplasty of the only patent renal artery - treatment of choice
      for end-stage heart failure.
AB  - The causes leading to the exacerbation of preexisting chronic heart failure can
      be various. Renal artery stenosis is an important cause of renal dysfunction, and
      can lead to worsening of heart failure and increased mortality. We present a 49
      year old male patient after acute myocardial infarction, heart failure with left
      ventricle ejection fraction of 20%, permanent atrial flutter, peripheral vascular
      disease, chronic kidney disease and arterial hypertension. In 2008 the patient
      underwent stenting of the left renal artery. At that time there was only discrete
      stenosis of the right renal artery. Two years later the patient presented with
      exacerbation of bi-ventricular chronic heart failure and renal failure. The
      echocardiography revealed dramatically reduced systolic function of both
      ventricles. As no response to intravenous diuretics was achieved, the patient
      underwent several courses of hemodialysis. Before considering the patient as a
      potential candidate for orthotopic heart transplantation, color Doppler
      ultrasound showed the occlusion of the left renal artery and significant stenosis
      of the right renal artery, which was stented. After the procedure spectacular
      clinical improvement was observed. The results of two randomized trials, ASTRAL
      and STAR, were discouraging for invasive treatment of renal artery stenosis.
      Still, serious doubts regarding the methodology of the studies were raised. Renal
      artery stenting may be the treatment of choice in highly selected patients and
      lead to clinical improvement. 

PMID- 24570692
TI  - Percutaneous balloon aortic valvuloplasty in different age groups.
AB  - Aortic stenosis is a congenital or acquired reduction in the area of the aortic
      valve, resulting in obstruction of the blood flow from the left ventricle to the
      aorta. Aortic stenosis accounts for 2-5% of all congenital heart defects and is a
      potentially life-threatening disorder. In adults aortic stenosis represents 34%
      of all valvular heart diseases. Degenerative etiology is present in 80% of cases.
      Patients with mild aortic stenosis are usually asymptomatic. Symptoms of the
      disease occur along with the disappearance of effective compensatory mechanisms.
      These are symptoms of low cardiac output syndrome manifested as fainting,
      dizziness, ischemic pains, exercise intolerance, arrhythmias with the risk of
      sudden cardiac death, and heart failure. As soon as the symptoms occur the
      prognosis significantly worsens, which is associated with a high risk of death.
      Percutaneous aortic valvuloplasty is a palliative method of treatment of aortic
      stenosis. The aim of the procedure is to relieve left ventricular outflow tract
      obstruction, thereby improving cardiac output. The etiology, course of the aortic
      stenosis and treatment methods, including invasive procedures, vary depending on
      the patients' age. The purpose of this paper is to present the characteristics of
      the aortic valve disease and the strategy of aortic balloon valvuloplasty in
      different age groups. 

PMID- 24570695
TI  - Large coronary artery fistula and patent ductus arteriosus: transcatheter closure
      with three PDA nitinol wire mesh occluders.
AB  - Coronary artery fistulas (CAF) are the most common congenital anomaly of this
      vessel. We present the case of a 26-year-old man with two coexisting congenital
      cardiac defects: patent ductus arteriosus (PDA) and CAF. The patient 3 months
      earlier had the transcatheter PDA closed (type A, diameter 4 mm) with a 10/8 mm
      PDA nitinol wire mesh occluder. After the procedure he continued to have symptoms
      of fatigue and continuous murmur in the precordial region persisted. In angio-CT
      a large coronary fistula from the circumflex coronary artery with suspicion of
      multiple orifices to the right atrium was found. An arteriovenous wire loop was
      created (guidewire introduced from the aorta through the CAF was snared using a
      lasso catheter in the superior vena cava and exteriorized through the right
      femoral vein). Retrogradely an 8 F long sheath and delivery system was introduced
      to the end of the fistula and a 12/10 mm Cardio-O-Fix PDA occluder (Starway Comp,
      China, Beijing) was implanted, closing one orifice of the CAF. Another leak
      (orifice of CAF - 3.5 mm diameter) was closed using a similar technique with a
      10/8 mm PDA Cardio-O-Fix device. Complete closure of the coronary artery fistula
      and disappearance of the heart murmur were observed after the procedure. The
      patient was discharged home 4 days later on acetylsalicylic acid 150 mg/day.
      During 6 months of follow-up he was doing well without any complaints or
      pathological symptoms. In control angio-CT performed 3 months after the procedure
      complete closure of the CAF was confirmed. 

PMID- 24570696
TI  - Closure of patent ductus arteriosus with oversized Amplatzer occluder in a
      patient with pulmonary hypertension.
AB  - Diagnosis of patent ductus arteriosus is rare in adulthood. Closure of ductus is
      difficult when diagnosed at an adult age due to the development of pulmonary
      hypertension and pulmonary arterial disease that generally occurs. Closure of the
      ductus might be contraindicated, as it may lead to deterioration of the pulmonary
      arterial perfusion or to a pulmonary hypertensive crisis. In addition, another
      risk associated with percutaneous closure for these patients is the risk of
      embolism of the asymmetrically shaped device to the systemic circulation. We
      present in this manuscript a case with patent ductus arteriosus diagnosed at an
      adult age that underwent successful closure by the percutaneous method. During
      closure, an oversized Amplatzer duct occluder device was used to reduce the risk
      of device embolism. 

PMID- 24570697
TI  - Cardiac arrest due to left circumflex coronary artery embolism as a complication
      of subtherapeutic oral anticoagulation in a patient with mitral and aortic
      mechanical valve prostheses.
AB  - We report a case of a 65-year-old female patient after replacement of aortic and
      mitral valve with mechanical prostheses and implantation of a pacemaker
      hospitalized in our clinic due to acute coronary syndrome complicated with
      cardiac arrest due to ventricular fibrillation. The electrocardiogram performed
      on admission showed signs of myocardial infarction with concomitant ventricular
      pacing. After successful resuscitation the coronary angiography was performed,
      which showed occlusion of the left circumflex artery (LCx) by thrombus. On the
      basis of intravascular ultrasound imaging the presence of vulnerable plaque,
      parietal thrombus and dissection of LCx were excluded. It suggested that
      occlusion of the LCx resulted from its embolism by left-sided heart thrombus due
      to subtherapeutic oral anticoagulation. In this case suboptimal anticoagulation
      was partially iatrogenic. Two weeks before the patient had been given vitamin K
      intravenously due to indeterminable international normalized ratio (INR) level,
      which caused transient resistance to oral anticoagulants. This case report
      illustrates tragic difficulties in the treatment with vitamin K antagonists,
      which concern as many as 2/3 of anticoagulated patients. These troubles
      contributed to the search for new, more efficient and safer anticoagulants. There
      are two classes of new oral anticoagulant drugs, which do not require monitoring
      of coagulation: direct thrombin inhibitors (e.g. dabigatran) and factor Xa
      inhibitors (e.g. rivaroxaban). In spite of their proven efficacy in the
      prevention of ischaemic stroke related to atrial fibrillation and prevention or
      treatment of deep vein thrombosis and pulmonary embolism, the use of new oral
      anticoagulants for the treatment of patients with mechanical valve prostheses
      needs further research. 

PMID- 24570698
TI  - Left anterior descending artery percutaneous coronary intervention via the left
      internal mammary artery in a 54-year-old type 1 diabetic woman: a case report.
AB  - Data on the treatment of left anterior descending artery (LAD) stenosis involving
      or localized distally to left internal mammary artery anastomosis are scarce and
      not homogeneous. Both surgery (CABG) and percutaneous interventions (PCI) have
      been attempted, but the most effective treatment has not yet been established. We
      report a case of a 54-year-old woman suffering from chronic, stable angina and
      diabetes type 1 successfully treated with percutaneous angioplasty of LAD via the
      left internal mammary artery with drug-eluting stent implantation with excellent
      short-term results. 

PMID- 24570699
TI  - Transient cortical blindness after coronary artery angiography.
AB  - Coronary angiography is the current gold standard for the diagnosis of ischemic
      heart disease and therefore the prevalence of percutaneous coronary procedures
      such as angiography and angioplasty is high. The occurrence of cerebral
      complications after coronary angiography and coronary angioplasty is low and it
      mainly includes transient ischemic attack and stroke. The prevalence of transient
      cortical blindness after X-ray contrast media is low and it is usually seen after
      cerebral angiography. Until now only a few cases of transient cortical blindness
      have been described after coronary artery angiography. Regarding the spread of
      coronary angiography worldwide and in Poland this complication is uniquely rare.
      A 32-year-old man with multiple extrasystolic ventricular arrhythmia suggesting
      Brugada syndrome diagnosis according to morphology of the left bundle branch
      block and with decreased left ventricular ejection fraction was admitted to the
      First Department of Cardiology and Hypertension, Medical College of the
      Jagiellonian University in Krakow. Coronary angiography was performed in order to
      exclude ischemic etiology of the observed abnormalities. No arteriosclerotic
      lesions were found in coronary arteries. Transient cortical blindness was
      observed directly after angiography which may have been caused by the neurotoxic
      effect of the used X-ray contrast medium. In ophthalmologic and neurologic
      examination as well as in the cerebral computed tomography scan no pathologies
      were found. Visual impairment disappeared totally within several hours. 

PMID- 24570700
TI  - Life-saving necklace: collateral circulation from the conus artery to the
      anterior descending artery.
AB  - We report a case of hyperacute inferior myocardial infarction with life-saving
      collateral circulation from the conus artery to the left anterior descending
      artery. 

PMID- 24570701
TI  - Spontaneous coronary artery dissection diagnosed by multislice computed
      tomography.
AB  - Spontaneous coronary artery dissection is a rare cause of acute coronary
      syndrome. Spontaneous coronary artery dissection can cause stable angina
      pectoris, unstable angina pectoris, acute myocardial infarction, cardiogenic
      shock and sudden cardiac death. It usually occurs in young to middle aged women.
      Atherosclerosis, peripartum period, and structural and inflammatory diseases
      affecting the artery wall are predisposing factors. It shows similar clinical
      presentation to coronary artery disease. Diagnosis and early treatment decrease
      mortality. Treatment options are medical treatment, percutaneous coronary
      intervention and surgery. The treatment decision is made according to the
      clinical presentation of the patient, the affected coronary artery and the length
      of the dissected segment. Diagnosis of the disease is usually made by coronary
      angiography. We present a patient who consulted our clinic with atypical chest
      pain and was diagnosed with spontaneous left anterior descending dissection by
      coronary computed tomography angiography. 

PMID- 24570702
TI  - Relation between coronary plaque calcium deposits as described by computed
      tomography coronary angiography and acute results of stent deployment as assessed
      by intravascular ultrasound.
AB  - INTRODUCTION: The findings from intravascular ultrasound studies on the impact of
      calcium deposits on the results of stent implantation are conflicting. AIM: To
      evaluate whether calcium deposits as assessed by (CTCA) influence results of
      stent deployment. MATERIAL AND METHODS: The study population comprised 60
      patients (43 male; age 64.2 +/-8.6 years) who underwent CTCA before stent
      implantation. Lesion calcium score, total calcium length, and maximal area and
      maximal thickness of calcium deposits within the lesion segment were assessed.
      Plaques were divided into those with calcium score >= median (group 1), calcium
      score < median (group 2), and without calcium (group 3). Intravascular ultrasound
      (IVUS) was performed after attainment of optimal angiographic results of the
      stent procedure. Focal and diffuse stent expansion was defined as either minimum
      stent area (MSA) or mean stent area over the length of the stent divided by
      reference lumen area. RESULTS: The proximal reference segments of lesions with
      higher calcium score contained a larger plaque burden (47 +/-12% vs. 41 +/-9% vs.
      34 +/-18%, p = 0.02) - respectively for groups 1, 2, and 3. Positive correlation
      was observed between lesion calcium score and frequency of post-dilation (R =
      0.28, p = 0.03). There was no difference in focal stent expansion (71 +/-14% vs.
      65 +/-15% vs.71 +/-15%, p = 0.3) or diffuse stent expansion (92 +/-30% vs. 85 +/
      30% vs. 93 +/-38%, p = 0.7) comparing groups 1, 2, and 3. Lesion calcium score,
      total length of calcium, and maximum area and thickness of calcium deposits did
      not correlate with focal or diffuse stent expansion. CONCLUSIONS: Lesions with a
      higher CTCA calcium score had larger reference plaque burden after stent
      implantation and more likely required post-dilation, but final stent expansion as
      assessed by IVUS was not affected by the amount of CTCA calcium provided an
      angiographically optimal result was achieved.

PMID- 24570703
TI  - Comparison of short-term outcomes after carotid artery stenting according to
      different stent designs.
AB  - INTRODUCTION: In the developed countries, stroke is the third most common cause
      of death. There are many data indicating that stents reduce the risk of embolism
      but there are few publications assessing whether different stent designs can
      influence the periprocedural complications. AIM: To determine the effects of open
      and closed-cell stent designs on 1-month results of carotid artery stenting
      (CAS). MATERIAL AND METHODS: The study group consisted of 290 consecutive
      patients (216 men and 74 women, mean age 66.6 +/-8.7 years). Neuroprotection with
      a distal protection device was used in all cases. The patients were divided into
      two groups: the open-cell stent group (n = 144) and the closed-cell stent group
      (n = 138). Major adverse cardiac and cerebrovascular events (MACCE) described as
      myocardial infarction, stroke and death within 1 month were recorded and analysed
      subsequently. Periprocedural hypotension and transient cerebral ischaemia at 1
      month after the CAS procedure were also assessed. RESULTS: We treated 290 carotid
      stenoses and stents were implanted in all patients. Fifteen patients (5.5%) were
      treated by staged CAS due to bilateral carotid artery disease. The technical
      success rate was 97.2%. There was no difference in the MACCE and transient
      cerebral ischaemia rate at 1 month between the two groups (p = 0.44 and p = 0.94,
      respectively). The incidence of ischaemic stroke was lower in the closed-cell
      stent group (2.77% vs. 0%; p = 0.04). The periprocedural rate of hypotension was
      higher in the closed-cell stent group (2.1% vs. 7.2%; p = 0.04). CONCLUSIONS:
      Closed-cell stents are associated with a low rate of ischaemic stroke. We think
      that closed-cell stents may be preferred in patients at high risk of embolism.

PMID- 24570704
TI  - Percutaneous reduction of mitral valve regurgitation using the MitraClip system -
      immediate and 90-day follow-up of 3 cases.
AB  - Treatment of hemodynamically significant valvular heart diseases has been the
      domain of cardiac surgery for decades. However, a promising novel method is the
      MitraClip system, involving percutaneous connection of insufficient valve
      leaflets with special cobalt-chrome clips. Our study presents clinical
      characteristics, course of treatment with the MitraClip system, and immediate and
      90-day clinical and echocardiographic follow-up of the first 3 patients treated
      in our institution. Subsequently, based on data from the literature and our own
      experience, the current position around the world, and the target group of
      patients who are most likely to benefit from treatment using the MitraClip
      system, are discussed. 

PMID- 24570705
TI  - Less invasive percutaneous closure of persistent arterial duct in children below
      10 kilos.
AB  - INTRODUCTION: There is quite high risk of vascular complications connected with
      arterial puncture - mainly in the group of the smallest patients weighing less
      than 10 kg. AIM: To evaluate a new method of percutaneous closure of persistent
      arterial duct (PDA) in small children. MATERIAL AND METHODS: Six patients were
      enrolled in this method of PDA closure at the age of 10.67 +/-1.97 months. The
      mean weight was 8.85 +/-0.66 kg. The occluders were implanted using only venous
      access. The position of the occluder was determined by angiography in the
      pulmonary artery through the delivery system and by echocardiography. RESULTS:
      The procedure was effective in all six cases but we managed to proceed in the
      planned transvenous method in five cases. There was one case of complete duct
      constriction after introduction of the catheter, so precise measurements were
      impossible. After removal of the catheter the constriction remitted completely.
      The duct was closed in the standard manner. During echocardiographic examination
      we found complete closure of all six arterial ducts directly after the procedures
      and in the follow-up (9.17 +/-3.02 months). No stenosis within the pulmonary
      arteries or aorta were found. CONCLUSIONS: Transcatheter arterial duct occlusion
      without arterial puncture is an effective and safe method of treatment allowing
      one to reduce the complications connected with arterial puncture. A possible
      complication of this method may be a constriction of the duct walls as a result
      of a larger amount of manipulations.

PMID- 24570707
TI  - Reconstruction of the left-sided brachiocephalic trunk after vascular ring
      operation in left-handed child with Kommerell's diverticulum.
AB  - We report a case of a 2-year-old girl with prenatal diagnosis of vascular ring
      composed of a right-sided aortic arch, a left ligamentum arteriosum, and a left
      subclavian artery (arteria lusoria sin) originating from a retroesophageal
      Kommerell's diverticulum, who was referred for surgery with symptoms related to
      local compression - severe dysphagia and respiratory disorders. Through the left
      posterolateral thoracotomy, a ligamentum arteriosum between the Kommerell's
      diverticulum and the left pulmonary artery was divided and because of left
      handedness of the child a brachiocephalic trunk was reconstructed in the fashion
      of anastomosis of the left subclavian artery and the left common carotid artery,
      originating from the ascending aorta. 

PMID- 24570706
TI  - Percutaneous coronary intervention in treatment of multivessel coronary artery
      disease in patients with non-ST-segment elevation acute coronary syndrome.
AB  - Among patients with non-ST-elevated acute coronary syndromes (NSTE-ACS) the
      estimated percentage of single vessel coronary artery disease (SV-CAD) observed
      during coronarography is about 20-40%, while multivessel coronary artery disease
      (MV-CAD) is found in about 40-60%. Further treatment in patients with both SV CAD
      and MV CAD is usually culprit vessel percutaneous coronary intervention (CV-PCI).
      Nevertheless, in the group of patients with MV-CAD there is still a problematic
      decision whether the non-infarct related arteries (non-IRA) should be treated
      with PCI. According to the European Society of Cardiology (ESC) guidelines on
      myocardial revascularization this decision should be based on the overall
      clinical and angiographic status of the patient; simultaneously they suggest
      performing ad hoc CV-PCI. The decision of performing intervention in the rest of
      the narrowed coronary arteries should be made after consultation with the heart
      team or according to the protocols adopted in the specific clinic. Furthermore,
      there is a question of whether the procedure should be performed immediately
      after culprit vessel revascularization or it should be postponed until the
      patient is stabilized. Due to the lack of specific recommendations we decided to
      perform an analysis of existing studies which compared culprit versus multivessel
      revascularization in patients with MV-CAD and non-ST-elevated acute coronary
      syndromes. 

PMID- 24570708
TI  - Acute coronary syndrome as a result of left main coronary artery stenosis after
      aortic valve replacement. A report of three cases.
AB  - Acute coronary syndrome (ACS) as a result of iatrogenic coronary ostial stenosis
      (ICOS) is a rare but potentially life-threatening complication of aortic valve
      replacement (AVR). We present three cases of patients with ACS shortly after AVR,
      in whom ICOS were revealed. They refused an operation and thus they were treated
      with percutaneous coronary intervention. The potential pathomechanisms of ICOS
      and treatment options are discussed. 

PMID- 24570709
TI  - Coronary computed tomography angiography in planning of percutaneous coronary
      interventions in bifurcation lesions - study design and rationale.
AB  - Percutaneous treatment of coronary bifurcations is a complex issue due to
      numerous possible techniques and high risk of complications. Because of
      increasing interest in non-invasive imaging in interventional cardiology and
      growing quality of obtained images, we designed a prospective, randomized, single
      blinded trial to evaluate the role of coronary computed tomography angiography
      (CCTA) in the planning of percutaneous coronary interventions (PCI) of
      bifurcation lesions. Eighty eligible patients scheduled for PCI of bifurcations
      in stable coronary artery disease will undergo additional CCTA examination and
      will be randomized 1: 1 to either planning of PCI using angiography and CCTA or
      to PCI planning with use of angiography alone. Primary endpoints will include PCI
      strategy (one or two stents), technique, size of implanted stents and direct
      angiographic effect of the procedure. Immediate PCI effect measured with
      intravascular ultrasound (IVUS) and the effect on fractional flow reserve (FFR)
      in the side branch (in a subgroup of patients), as well as plaque morphology
      assessed in CCTA, patient radiation exposure and amount of contrast will be
      compared in secondary analysis. The study is intended to clarify the influence of
      CCTA analysis on the technique and direct effect of PCI of bifurcations and to
      provide evidence on the relevance of performing a CCTA scan prior to PCI of
      bifurcation lesions. 

PMID- 24570711
TI  - Calculating the overall risk of within-stent restenosis after multilesion
      percutaneous coronary intervention.

PMID- 24570710
TI  - Invasive and non-invasive fractional flow reserve index in validation of
      hemodynamic severity of intracoronary lesions.
AB  - This review discusses visual and functional evaluation of the hemodynamic
      significance of the degree of stenosis in coronary angiography, with respect to
      the indications for revascularization. The concept of the coronary flow reserve
      is defined, and the theoretical assumptions of the invasive measurement of the
      fractional flow reserve (FFR) are presented. In the following part, the
      publication describes the basic steps of numerical stimulations in terms of
      computational fluid dynamics (CFD) in calculating the fractional flow reserve
      based on computed tomography (CT) coronary angiography (FFRCT). The numerical
      FFRCT estimation in correlation with invasive measurements, as well as benefits
      deriving from FFRCT in the diagnosis of coronary artery disease, is presented in
      the example of the multicentre prospective DISCOVER-FLOW trial and the DeFACTO
      project. The CDF method enables to obtain hemodynamic significance of stenosis
      solely from the coronary anatomy vizualized by CT angiography. The calculation of
      FFRCT increases the diagnostic reliability of coronary flow reserve estimations.
      It contributes to the improvement in patients' qualification for contrast
      coronarography. If the accuracy of FFRCT is confirmed in clinical practice, and
      the time required for computational processing is shortened, it may turn out that
      the algorithms of coronary heart disease diagnosis will be verified and it will
      be to a greater extent based on the CT results. 

PMID- 24570712
TI  - Rescue percutaneous coronary recanalization of right coronary artery by
      retrograde approach.
AB  - We describe the case of a 62-year-old female patient in whom there was an
      occlusion of collaterals and acute inferior wall ischemia during the opening
      procedure of right coronary artery (RCA) chronic total occlusion. Rescue
      percutaneous coronary intervention (PCI) of RCA by the retrograde approach was
      performed preventing heart muscle damage. In this article we discuss the issue of
      PCI by the retrograde technique. 

PMID- 24570713
TI  - A very rare case of coexistence of ventricular noncompaction cardiomyopathy,
      myocardial bridging and atherosclerosis.
AB  - Noncompaction of the ventricular myocardium is a rare congenital heart disease,
      presumably caused by the intrauterine arrest of the myocardial compaction process
      at the beginning of fetal development. It could remain asymptomatic or manifest
      with congestive heart failure, arrhythmias, and systemic thromboemboli. Here we
      report a 55-year-old man who was admitted to hospital with chest pain and
      dyspnea, whose further evaluation revealed left ventricular noncompaction
      cardiomyopathy accompanying myocardial bridging and stenosis of the right
      coronary artery. 

PMID- 24570714
TI  - Acute coronary syndrome in a 100-year-old woman treated successfully with primary
      percutaneous coronary angioplasty.
AB  - We present a case of a 100-year-old woman living alone with ST-elevation
      myocardial infarction acute coronary syndrome of the infero-lateral wall treated
      with percutaneous coronary intervention. Coronary angiography revealed critical
      99% stenosis in the marginal branch of the circumflex artery and insignificant
      lesions in other arteries. Two bare metal stents were implanted successfully in
      the same session. The patient was discharged home in good general condition, able
      to live and function independently. 

PMID- 24570715
TI  - A case of acute brachial artery occlusion after transradial coronary
      intervention.
AB  - In 2010, a 49-year-old man was admitted to our hospital with chest pain.
      Angiography via the radial approach was performed. Acute brachial artery
      occlusion was present after the procedure. By transcatheter thrombolysis,
      brachial artery occlusion was recanalized. Transcatheter thrombolysis seemed to
      be effective and safe. 

PMID- 24570716
TI  - Proximal ductus arteriosus stenosis after the hybrid stage I procedure in a
      newborn with hypoplastic left heart syndrome.
AB  - We present a case of a severely ill newborn with hypoplastic left heart syndrome
      after the hybrid stage I procedure, with right systemic ventricle insufficiency
      due to proximal ductus arteriosus stenosis. The child was successfully treated
      with percutaneous second PDA stent implantation. 

PMID- 24570717
TI  - Stent entrapment and guide wire fracture during percutaneous coronary
      intervention in the same patient.
AB  - In the performance of increasingly complex PCI there remains an ever-present risk
      of stent entrapment and guide wire or other device fracture. We report the first
      case with stent dislodgement and guide wire fracture to occur simultaneously in
      the same patient. 

PMID- 24570718
TI  - Spontaneous resolution of iatrogenic dissection of the left main coronary artery
      extending to the thoracic and abdominal aorta.
AB  - Iatrogenic coronary artery dissection extending to the ascending aorta is a rare
      complication of percutaneous coronary interventions. Coronary stent implantation
      is usually sufficient to control the injury. In this report we describe an
      unusual case of spontaneous resolution of both left main coronary artery and
      aortic wall dissection. The patient was not operated on due to the location of
      the initial tear in the distal part of the left main coronary artery. Moreover,
      in computed tomography (CT) thrombus formation in the false lumen of the
      dissected aorta was seen. The in-hospital course was uneventful. The last follow
      up CT showed complete resolution of dissection. 

PMID- 24570719
TI  - Lidocaine bolus may facilitate computed tomographic coronary angiography in
      patients with frequent premature ventricular contractions.
AB  - INTRODUCTION: Heart rate irregularities are the major limitations of computed
      tomographic coronary angiography (CTCA) due to severe motion artifacts. AIM: To
      evaluate the safety and efficacy of a lidocaine intravenous bolus in preserving
      good image quality by the transient suppression of premature ventricular
      contractions (PVC) during the CTCA scan. MATERIAL AND METHODS: The study group
      comprised 67 consecutive patients with sinus rhythm and numerous PVC scheduled
      for CTCA. Intravenous boluses of 25-50 mg lidocaine were given after calcium
      score assessment and immediately before CTCA. The control group comprised 67
      patients with sinus rhythm without PVC matched according to the body mass index
      (BMI), age, sex, and calcium score. All coronary vessel segments were assessed
      for image quality and presence of significant stenosis. RESULTS: As compared with
      calcium score assessment, after administration of lidocaine and during the CTCA
      scan PVC were completely suppressed in 22 (40%), reduced in 10 (18%), unchanged
      in 18 (32%), and intensified in 5 (10%) patients. Overall, there were 32 (58%)
      patients with sinus rhythm during CTCA as compared with only 11 (20%) patients
      free from PVC during calcium score assessment (p < 0.001). Image quality in 871
      coronary segments including both the study group and control patients was worse
      in patients with PVC (p < 0.0001). However, there was no statistically
      significant difference in the number of patients with at least one segment of non
      diagnostic quality (6% vs. 12%, p = 0.36; respectively). CONCLUSIONS: Single
      lidocaine bolus given prior to CTCA is safe, may temporarily eliminate or reduce
      the intensity of arrhythmia, and hence results in improved quality of CTCA in
      patients with numerous PVC.

PMID- 24570720
TI  - Evaluation of morphological characteristics of septal rims affecting successful
      transcatheter atrial septal defect closure in children and adults.
AB  - INTRODUCTION: Determining other echocardiographic predictors along with the
      measured atrial septal defect (ASD) size and evaluating the closure together with
      these predictors would increase the chance of success for transcatheter closure
      of ASD. AIM: To evaluate echocardiographic parameters affecting defect closure in
      children and adult patients with secundum ASD. MATERIAL AND METHODS: In all
      patients, size of ASD, total length of atrial septum (TS), superior-posterior,
      inferior-posterior, superior-anterior and inferior-anterior rims surrounding the
      defect were measured by transesophageal echocardiography (TEE), and several
      measurement ratios were derived on the basis of TEE parameters. RESULTS: A total
      216 patients with secundum ASD were included in this study. The device was
      successfully implanted in 65 children and 65 adults. Both in pediatric and adult
      cases, the ratio of successful closure was found to be significantly higher when
      the ratio of defect size to TS was <= 0.35, the ratio of superior-anterior (SA)
      rim to the defect size was > 0.75 and the ratio of inferior-posterior (IP) rim to
      the defect size was > 1.0. It was found that having more than one of these
      predictors in a single case increased the chance of closure success significantly
      (p < 0.001). CONCLUSIONS: We concluded that a ratio of the defect size to TS <=
      0.35, a ratio of SA rim to defect size > 0.75 and a ratio of IP rim to defect
      size > 1.0 were found to be echocardiographic predictors that could be used in
      successful transcatheter ASD closure both in children and adults.

PMID- 24570721
TI  - Risk is not flat. Comprehensive approach to multidimensional risk management in
      ST-elevation myocardial infarction treated with primary angioplasty (ANIN STEMI
      Registry).
AB  - INTRODUCTION: Current risk assessment concepts in ST-elevation myocardial
      infarction (STEMI) are suboptimal for guiding clinical management. AIM: To
      elaborate a composite risk management concept for STEMI, enhancing clinical
      decision making. MATERIAL AND METHODS: 1995 unselected, registry patients with
      STEMI treated with primary percutaneous coronary intervention (pPCI) (mean age
      60.1 years, 72.1% men) were included in the study. The independent risk markers
      were grouped by means of factor analysis, and the appropriate hazards were
      identified. RESULTS: In-hospital death was the primary outcome, observed in 95
      (4.7%) patients. Independent predictors of mortality included age, leukocytosis,
      hyperglycemia, tachycardia, low blood pressure, impaired renal function, Killip >
      1, anemia, and history of coronary disease. The factor analysis identified two
      significant clusters of risk markers: 1. age-anemia- impaired renal function,
      interpreted as the patient-related hazard; and 2. tachycardia-Killip > 1
      hyperglycemia-leukocytosis, interpreted as the event-related (hemodynamic)
      hazard. The hazard levels (from low to high) were defined based on the number of
      respective risk markers. Patient-related hazard determined outcomes most
      significantly within the low hemodynamic hazard group. CONCLUSIONS: The
      dissection of the global risk into the combination of patient- and event-related
      (hemodynamic) hazards allows comprehensive assessment and management of several,
      often contradictory sources of risk in STEMI. The cohort of high-risk STEMI
      patients despite hemodynamically trivial infarction face the most suboptimal
      outcomes under the current invasive management strategy.

PMID- 24570722
TI  - Comparison of anti-embolic protection with proximal balloon occlusion and filter
      devices during carotid artery stenting: clinical and procedural outcomes.
AB  - AIM: The objective of this study was to compare the periprocedural and clinical
      outcomes after carotid artery stenting (CAS) with proximal protection devices
      versus with distal protection devices. MATERIAL AND METHODS: Patients with
      internal carotid artery (ICA) stenosis undergoing CAS with cerebral embolic
      protection were randomly assigned to proximal balloon occlusion or distal filter
      protection. Adverse events were defined as death, major stroke, minor stroke,
      transient ischemic attack (TIA) and myocardial infarction (MI). Periprocedural
      and 30-day adverse events and ICA vasospasm rates were compared between the two
      embolic protection groups. RESULTS: Eighty-eight consecutive patients were
      randomized: 48 patients with proximal protection (mean age 68.8 +/-13.6, 66%
      male) and 40 patients with a distal protection device (mean age 65.4 +/-12.3; 70%
      male). There was no significant difference in periprocedural or 30-day adverse
      event rates between the two groups (p > 0.05). However, there was a higher
      periprocedural ICA vasospasm rate in the distal filter protection group (9
      patients, 23%) compared with the proximal balloon occlusion group (1 patient, 2%)
      (p = 0.019). CONCLUSIONS: There was no difference between the clinical
      periprocedural and 30-day adverse event rates of distal filter and proximal
      balloon protection systems. However, distal filter protection systems showed
      higher rates of periprocedural ICA vasospasm.

PMID- 24570723
TI  - Clinical outcomes and effectiveness of renal artery stenting in patients with
      critical atherosclerotic renal artery stenosis: does it improve blood pressure
      control and renal function assessed by estimated glomerular filtration rate?
AB  - INTRODUCTION: Atherosclerotic renal artery stenosis (ARAS) is associated with
      uncontrolled hypertension and chronic renal failure. AIM: To evaluate the
      influence of gender and presence of chronic renal failure on the outcomes of
      percutaneous transluminal renal artery stenting (PTRAS) due to atherosclerosis.
      MATERIAL AND METHODS: A total of 28 ARAS patients underwent PTRAS and 36 stents
      were placed. Basal characteristics, laboratory data and blood pressure of
      patients were recorded. The differences between genders and
      improvement/deterioration of renal functions and blood pressure were analyzed.
      The predictors of outcomes were determined. RESULTS: Baseline characteristics
      were similar between men and women. Significant improvement of systolic and
      diastolic blood pressure control was achieved after PTRAS (153.04 +/-17.07 mm Hg
      vs. 124.75 +/-11.40 mm Hg, p = 0.001 and 92.50 +/-10.76 mm Hg vs. 77.54 +/-8.23
      mm Hg, p < 0.001, respectively). Although mean estimated glomerular filtration
      rate (eGFR) and creatinine levels did not significantly improve at the 6-month
      follow-up visit compared to baseline values, of the 28 patients 13 (46.4%)
      patients had improvement of renal functions. CONCLUSIONS: Our results suggest
      that PTRAS is a safe procedure and may offer blood pressure control but
      beneficial effects of PTRAS on renal function may be anticipated in a selected
      group of patients, especially those with a low eGFR.

PMID- 24570724
TI  - Balancing between bleeding and thromboembolism after percutaneous coronary
      intervention in patients with atrial fibrillation. Could triple anticoagulant
      therapy be a solution?
AB  - INTRODUCTION: Atrial fibrillation (AF) has nowadays become a common disease as it
      comes along with medical procedures propagation in the ageing population with
      coexistent diseases. Hence a need for use of combined anticoagulant and
      antithrombotic therapy has arisen. According to the 2010 ESC guidelines on
      myocardial revascularization, short-term triple antithrombotic therapy after
      percutaneous coronary intervention (PCI) should be given if compelling
      indications exist. AIM: To assess bleeding and thromboembolic events depending on
      the antithrombotic regimen in short- and long-term follow-up in patients with AF
      after PCI with stent implantation. MATERIAL AND METHODS: A 12-month prospective,
      non-randomized registry was conducted in the 3(rd) Department of Cardiology in
      the Upper Silesian Medical Center in Katowice from October 2008 to April 2011.
      One hundred and four patients in two groups - on triple therapy (TT; aspirin +
      clopidogrel + vitamin K antagonists (VKA; warfarin or acenocoumarol) n = 44) and
      on dual therapy (DT; aspirin + clopidogrel; n = 60) - were assessed 30 days and
      12 months after angioplasty. RESULTS: All bleeding events occurred more often in
      the triple anticoagulated group in 30 days (TT 20.5% vs. DT 6.7%; p = 0.03) and
      after 12 months (TT 38.9% vs. DT 17.2%, p = 0.09). The difference in major
      bleeding events was not significant after 30 days (TT 9.1% vs. DT 3.3%; p = NS)
      or 12 months (TT 11.1% vs. DT 6.9%; p = NS). Thromboembolic events after 30 days
      (DT 5.0% vs. TT 2.3%) and 12 months (TT 11.1% vs. DT 3.4%) were comparable. The
      percentage of deaths after 30 days (DT 1.7% vs. TT 0.0%, p = NS) increased after
      12 months (DT 13.8% vs. TT 0.0%, p = 0.09). CONCLUSIONS: Significantly higher
      risk of bleeding on TT becomes blurred by a tendency to increased mortality in
      patients on DT.

PMID- 24570725
TI  - Increased mean platelet volume is associated with coronary artery ectasia.
AB  - AIM: The present study was designed to investigate mean platelet volume (MPV)
      values in coronary artery ectasia (CAE) patients in comparison with individuals
      with coronary artery disease and normal coronary angiograms. MATERIAL AND
      METHODS: Patients with stable angina pectoris and scheduled for angiography were
      included in the study. Those with isolated coronary ectasia were evaluated in the
      coronary angiography. Mean platelet volume was measured in 126 patients (mean
      age: 57.2 +/-11.3 years) with isolated CAE, 126 patients (mean age: 56.3 +/-10.4
      years) with coronary artery disease (CAD) and 122 control subjects (mean age:
      58.1 +/-11.1 years). Coronary artery ectasia was defined as lack of stenotic
      lesion, on visual assessment, of the coronary arteries with a luminal dilatation
      1.5-fold or more of the adjacent normal coronary segments. Mean platelet volume
      values were recorded in all patients. Ectasia severity was evaluated and
      categorized in accordance with the Markis categorization. RESULTS: A significant
      difference with respect to age, sex, hypertension, diabetes mellitus, and
      cigarette use between the study groups was not found (p > 0.05). Mean platelet
      volume was significantly higher in patients with CAE and CAD than in the control
      group (9.8 +/-3.8 fl and 9.7 +/-3.9 fl vs. 8.8 +/-3.3 fl, p < 0.001). There were
      no statistically significant differences between CAE and CAD groups. When type I
      and type IV subgroups were compared in patients with coronary artery ectasia, MPV
      was detected as statistically high in the type I subgroup (p = 0.026).
      CONCLUSIONS: It was shown that patients with CAE and CAD have higher MPVs than
      subjects with normal coronary angiograms. Moreover, it was detected that in
      coronary artery ectasias, the increase in MPV is related to both the
      atherosclerotic process and severity of the disease.

PMID- 24570726
TI  - 74-year-old man with left main and carotid artery disease - how life can change
      plans.
AB  - An unexpected incident or rapid deterioration of a patient's condition may
      require optimal adaptation of the treatment to the current state of the patient.
      We present a case of a 74-year-old man with significant left main coronary artery
      stenosis and tight stenoses of both carotid arteries. The case was initially
      qualified for bypass grafting with accompanying carotid artery endarterectomy,
      but an unexpected accident changed our way of treatment. Three days after
      angiography the patient suffered an ischemic stroke. We held a multidisciplinary
      meeting of the "Neuro-Vascular-Heart Team" and decided to treat the patient
      percutaneously. 

PMID- 24570727
TI  - Myocardial infarction caused by pharmacological substances - case description and
      literature review.
AB  - Myocardial infarction (MI) is most commonly caused by atherosclerosis and/or
      inflammatory processes of coronary artery walls. The consequence of those
      phenomena is instability of the atherosclerotic plaque, activation of the
      coagulation cascade and thrombus formation which occludes the lumen of the
      vessel. Vasospasm and microembolisation may participate in MI pathogenesis. In
      young individuals with diagnosis of MI, coronarography often reveals no
      pathologies. Is reported that MIs without significant changes of the coronary
      arteries occur in 1% to 12% of patients. In this article we focus on chemical
      substances, medicines among them, which can be a cause of MI. 

PMID- 24570728
TI  - Arrhythmogenic right ventricular cardiomyopathy in a 52-year-old man - clinical
      presentation mimicking an acute coronary syndrome.
AB  - Arrhythmogenic right ventricular cardiomyopathy is an infrequently diagnosed,
      genetically determined disease that leads to significant clinical consequences,
      including progressive heart failure and ventricular arrhythmias accounting for
      sudden cardiac death. We report the case of a 52-year-old patient who presented
      with ventricular tachycardia and features of an acute coronary syndrome. However,
      routine tests excluded critical coronary stenosis and the final diagnosis was
      arrhythmogenic right ventricular cardiomyopathy. 

PMID- 24570729
TI  - Midterm results of sildenafil therapy in two complex patients with elevated
      pulmonary artery pressure after cavopulmonary connection.
AB  - Two cases are presented. In the first patient (8-year-old boy) after Glenn
      operation without closure of pulmonary outflow from the common ventricle (SV-PA)
      despite transcatheter SV-PA closure increased mean pulmonary artery pressure
      (mPAP) (22 mm Hg) remained. After 6 months of sildenafil therapy he was
      catheterized again. His mPAP dropped to 10 mm Hg and a Fontan operation was
      subsequently performed. The second patient was a 25-year-old man, 20 years after
      a Fontan operation, presenting protein losing enteropathy and severe heart
      failure. All syndromes diminished significantly after medical therapy with
      sildenafil. Good clinical results of sildenafil therapy were maintained after 1
      and 4 years of treatment. Chronic therapy with sildenafil can be beneficial in
      patients before and after the Fontan operation with elevated pulmonary artery
      pressure. 

PMID- 24570731
TI  - Patent foramen ovale and cryptogenic stroke - a statistical or cause-and-effect
      relationship? A neurological point of view.
AB  - Patent foramen ovale and atrial septal aneurysm are considered to be factors
      conducive to the occurrence of stroke and transient ischaemic attacks. However,
      there is no clear answer to the question whether patent foramen ovale is an
      independent risk factor for stroke and what the mechanism of potential cerebral
      ischaemia in patients with an interatrial septal abnormality is. The paper
      presents the results of studies regarding the issue, including epidemiological,
      clinical and neuroimaging data. The subject of secondary prevention in patients
      with cryptogenic stroke and patent foramen ovale, including the results of
      research into the effectiveness of pharmacological methods and percutaneous
      closure of interatrial septal defects, is raised. The available research results
      do not conclusively suggest a causal relationship between patent foramen ovale
      and stroke. There is a probable summative effect of atrial septal abnormality and
      other factors (haemostatic and genetic ones as well as those that are associated
      with cerebral vessels) leading to cerebral ischaemia. There are no indications
      for the use of anticoagulant treatment in patients with stroke and presence of
      patent foramen ovale. In patients at a high risk for stroke, invasive treatment
      should be considered, which is consistent with the position of the European
      Stroke Organisation. 

PMID- 24570730
TI  - A fatal outcome of thoracic aortic aneurysm in a male patient with bicuspid
      aortic valve.
AB  - Thoracic aortic aneurysm is often an asymptomatic but potentially lethal disease
      if its most catastrophic complication - aortic dissection - occurs. Thoracic
      aortic dissection is associated with a high mortality rate despite ongoing
      improvement in its management. We report a fatal outcome of thoracic aortic
      aneurysm in a male patient with bicuspid aortic valve. The patient was qualified
      for elective surgery of the ascending aorta and aortic valve at the age of 39 but
      he did not agree to undergo the proposed procedure. Three years later, he
      experienced acute aortic dissection and died despite a prompt diagnosis and
      complex management. 

PMID- 24570733
TI  - Optimal treatment of coronary-to-pulmonary artery fistula: surgery, coil or stent
      graft?
AB  - We report a case of a 57-year-old man with typical angina due to a coronary
      artery-to-pulmonary artery fistula, which was evident on transthoracic and
      transesophageal echocardiography with color Doppler flow mapping. The diagnosis
      was confirmed by coronary angiography. The patient underwent surgical ligation of
      the fistula. However, repeated transesophageal echocardiography and coronary
      angiography revealed persistence of the fistula with significant left-to-right
      shunt. The orifice of the fistula was then obliterated by stent-graft
      implantation, which was proven successful by angiography and echocardiography. 

PMID- 24570732
TI  - The impact of ischemia-reperfusion injury on the effectiveness of primary
      angioplasty in ST-segment elevation myocardial infarction.
AB  - The most effective method of reperfusion in patients with ST-segment elevation
      myocardial infarction (STEMI) is primary percutaneous coronary intervention
      (PCI), assisted by aspiration thrombectomy and administration of antiplatelet
      agents and anticoagulants. However, effective restoration of blood flow in the
      infarct-related artery may paradoxically result in further damage to the heart
      muscle. This phenomenon, called ischemia-reperfusion injury (IRI), can
      significantly reduce the beneficial effects of reperfusion therapy. The rapid
      restoration of blood flow to the previously ischemic area causes a number of
      pathophysiological mechanisms leading to increased necrosis of myocytes still
      viable at the end of the ischemic period. It has been postulated that there are
      several strategies that can reduce damage to the heart muscle. Attempts to
      translate the results of experimental trials has been disappointing. More
      recently, however, some of the clinical benefits of ischemic postconditioning in
      which reperfusion in patients with STEMI who are undergoing PCI is interrupted
      with short episodes of ischemia were demonstrated. This renewed the interest in
      the reperfusion phase as a target for cardioprotective therapy. Research in this
      field has also been reinforced by the discovery of new potential targets for
      treatment that protects against IRI, such as the kinase pathway to protect
      against damage (reperfusion injury salvage kinases - RISK) and mitochondrial
      permeability transition pore. It seems that these findings will help to develop
      strategies that will improve the efficiency of mechanical reperfusion and may
      translate into long-term clinical effects. 

PMID- 24570734
TI  - Successful percutaneous coronary intervention using a 4-in-3 "Slender Mother and
      Child" PCI technique.
AB  - We report two cases of successful percutaneous coronary intervention (PCI) using
      a 4-in-3 "Slender Mother and Child" PCI technique. In both cases, coronary
      angiography revealed severe stenosis of the right coronary artery (RCA). In both
      cases, 5-Fr sheathless guiding catheters were inserted into the RCA (virtual 3-Fr
      PCI) but stents could not pass through because of stents previously implanted at
      the proximal site of the target lesions. After 4-Fr straight "child" guiding
      catheters were inserted into the 5-Fr sheathless "slender mother" guiding
      catheters, they were deployed successfully at the target lesions. This system
      might be useful to improve stent delivery in virtual 3-Fr PCI. 

PMID- 24570735
TI  - Expanded indications for transcatheter renal denervation.
AB  - Renal denervation (RDN) is a catheter-based procedure introduced in 2009 as a
      treatment of resistant hypertension. The method is based on the concept that
      resistant hypertension is a result of hyperactivity of the sympathetic nervous
      system (SNS), and therefore reducing the impact of the SNS by ablating the renal
      nerves should eliminate the condition. Since 2009 numerous investigators have
      proven the procedure to be safe and effective, which contributed to the quick
      success and wide spread of the method, subsequently triggering further research
      in this area. The dynamic distribution of the procedure induced investigators to
      examine the influence of RDN on other conditions involving hyperactivity of the
      SNS (such as atrial fibrillation or ventricular arrhythmia). A few studies aiming
      to explain the influence of RDN on arrhythmias in patients with resistant
      hypertension have been conducted. The results in treating atrial fibrillation
      additionally to pulmonary vein ablation and electrical storm appear to be
      promising; however, the data are limited and further investigations needs to be
      done. The influence of RDN on insulin resistance, left ventricular hypertrophy
      and heart failure are possible. Perspectives of expanding indications are
      discussed. Renal denervation appears to be a promising way of treating
      hypertension and raises hope for a wider group of patients with conditions
      closely related to hyperactivity of the sympathetic nervous system such as
      arrhythmia. 

PMID- 24570736
TI  - Compressed valve in a calcified right ventricular outflow tract.

PMID- 24570738
TI  - Coronary artery perforation during diagnostic coronary angiography resulting in
      acute pericarditis.
AB  - We report a case of coronary artery perforation during diagnostic coronary
      angiography. No cardiac biomarker elevation was observed. However, the patient
      suffered acute pericarditis which was treated conservatively. 

PMID- 24570737
TI  - Circumflex-to-bronchial artery fistula with saccular aneurysm.
AB  - We report a case of fistulous communication with two saccular aneurysms (9 mm and
      7 mm) between the sinoatrial branch of the circumflex artery and the bronchial
      arteries. 

PMID- 24570739
TI  - Percutaneous retrieval of a detached rotational atherectomy burr.
AB  - Rotablation (rotational atherectomy) is an acknowledged method of percutaneous
      treatment of highly calcified coronary artery lesions that cannot be treated with
      traditional angioplasty. The complexity of the technique and usage of very
      specific equipment can contribute to the development of uncommon complications.
      We present a case of percutaneous retrieval of a damaged rotational atherectomy
      burr in a 74-year-old male patient. 

PMID- 24570740
TI  - Successful angioplasty for radial artery chronic total occlusion in a patient
      with digital gangrene.
AB  - Critical hand ischemia caused by chronic occlusive arterial disease is an
      uncommon condition. Diabetes mellitus and chronic renal insufficiency are the
      concomitant conditions in most of these patients. A 59-year-old woman with
      diabetic nephropathy being treated with hemodialysis was referred to the
      Cardiology Department for a non-healing necrotic lesion in the distal part of the
      fourth finger. We performed balloon angioplasty for diffuse and severe calcified
      total occlusion of the radial artery using long and high pressure resistant
      balloons. After successful angioplasty the symptoms were relieved immediately and
      the finger was almost healed within 2 months of follow-up. 

PMID- 24570741
TI  - Advanced peripheral arterial disease in a 59-year-old man with suspected acute
      coronary syndrome and normal coronary angiogram.
AB  - Atherosclerosis is a systemic process with variable expression in different
      vascular beds. Peripheral arterial disease (PAD) is thought to be found in 12% of
      the age-adjusted population. Reasons for differential anatomic expression of
      atherosclerosis may involve the interplay between inflammation, shear stresses,
      flow characteristics, and other local factors. It's well known that synchronous
      PAD and coronary artery disease is very common and is likely the result of the
      systemic impact of atherosclerotic risk factors. On the other hand, there are
      limited data concerning atherosclerotic process restricted to specific vascular
      areas in the human body. 

PMID- 24570742
TI  - One step behind to step ahead - femoral approach to stabilize and to extract
      functional pacing lead to regain venous access.
AB  - Transvenous lead extraction can be a method to regain venous access. We present
      the case of a man, aged 67, with indications to upgrade an ICD to a
      resynchronization therapy device. Since innominate vein occlusion was diagnosed
      and extraction of an abandoned ventricular pacing lead did not provide lumen
      regain, a functional atrial lead was extracted with the femoral approach to
      stabilization and venous access was regained. Asymptomatic vein wall damage but
      no other complications were recorded. The simultaneous application of different
      techniques to regain venous access may allow success of the final procedure in
      system upgrading. 

PMID- 24570743
TI  - Complex percutaneous coronary intervention of the left coronary artery with
      rotational atherectomy in an 84-year-old dialysed patient.
AB  - Coronary artery disease in patients with end-stage renal disease occurs several
      dozen times more often than in the general population. Atherosclerotic changes in
      coronary arteries in dialysed patients are more diffused and calcified, which
      hampers the percutaneous coronary angioplasty. We present a case of an 84-year
      old dialysed patient, in whom complex percutaneous coronary intervention of the
      left anterior descending artery was performed with the use of rotational
      atherectomy. 

PMID- 24570744
TI  - Ostial stenosis of the left main coronary artery as the result of the previous
      percutaneous coronary intervention on the left coronary artery.
AB  - A 76-year-old patient was admitted to hospital due to recurrent chest pain.
      Angiography revealed multivessel coronary artery disease with significant
      stenosis in medial and distal parts of the left main coronary artery (LMCA). Two
      drug-eluting stents (DES) were implanted from the medial part of the LMCA to the
      proximal part of the left anterior descending (LAD) artery. An excellent
      angiographic result was achieved. After 20 days the patient returned to our
      clinic because of acute coronary syndrome (ACS). Angiography showed 80% stenosis
      in the ostial LMCA. The lesion was stented with DES, obtaining a good
      angiographic result. 

PMID- 24570745
TI  - Report from the 12(th) Conference of the Pediatric Cardiology Section of the
      Polish Cardiac Society (Zabrze 7-8.06.2013) - "Progress in interventional
      treatment of congenital heart diseases".

PMID- 24570746
TI  - Plasma lipoprotein(a) levels in patients with slow coronary flow.
AB  - INTRODUCTION: Slow coronary flow (SCF) is a microvascular disorder characterized
      by delayed opacification of coronary vessels with normal coronary angiogram. It
      may be due to endothelial dysfunction and diffuse atherosclerosis. Lipoprotein(a)
      [Lp(a)] is related to cardiovascular events. Plasma Lp(a) levels have not been
      studied previously in SCF patients. AIM: We investigated plasma Lp(a) and
      fibrinogen levels, and their relation to coronary flow rate in patients with SCF.
      MATERIAL AND METHODS: This cross-sectional study included 50 patients with SCF
      and 30 age- and sex-matched controls who had normal coronary arteries and normal
      flow. Coronary flow rates of patients and controls were counted with the
      thrombolysis in myocardial infarction (TIMI) frame count. Plasma Lp(a) and
      fibrinogen levels were measured in SCF patients and controls, with routine
      biochemical tests. RESULTS: There were no significant differences between the two
      groups with respect to plasma Lp(a) (21 mg/dl vs. 14 mg/dl, p = 0.11) and
      fibrinogen (278 mg/dl vs. 291 mg/dl, p = 0.48) levels. The TIMI frame count was
      not correlated with plasma Lp(a) (r = 0.13, p = 0.25) or fibrinogen (r = -0.14, p
      = 0.28) levels. CONCLUSIONS: Our results show that there is no significant
      association between SCF and Lp(a) and fibrinogen levels.

PMID- 24570747
TI  - The clinical significance of anticardiolipin antibody levels in patients with
      acute myocardial infarction: a regional study.
AB  - INTRODUCTION: Acute myocardial infarction (AMI) will probably remain the most
      important cause of death over the next decades. Traditional risk factors of
      atherosclerosis could not exactly explain the development of acute coronary
      events such as AMI. Antiphospholipid antibody syndrome is a disorder
      characterized by the development of arterial and venous thrombosis. AIM: In this
      study, we investigated the relations between acute myocardial infarction and anti
      phospholipid antibody syndrome in our population representing Aegean Region
      people characteristics. MATERIAL AND METHODS: One hundred patients with acute
      myocardial infarction were consecutively included in the study (group I) and one
      hundred age and sex matched people with similar risk factors were enrolled in the
      study as a control group (group II). Anticardiolipin antibody (aCL) IgM and IgG
      levels were measured in the two groups. Levels of aCL IgG >= 48 U/ml and/or aCL
      IgM >= 44 U/ml were accepted as positive and significant. RESULTS: In patients
      with acute myocardial infarction, 5 patients (5%) had positive IgM levels and 8
      patients (8%) were found to have positive IgG levels. All cases in the control
      group had negative aCL IgM and IgG antibody levels. These results were accepted
      as significant for both aCL antibodies between patients and controls (p < 0.001).
      CONCLUSIONS: We concluded that aCL antibody levels are also higher in a small
      proportion of patients with acute myocardial infarction than controls in our
      region, also, and these results suggest that there may be an immune stimulus in
      the pathogenesis of acute coronary events.

PMID- 24570748
TI  - Evaluation of the usefulness of coronary catheters and 4 Fr insertion sets for
      transradial access coronarography in comparison with catheters and 5 Fr sets.
AB  - INTRODUCTION: Application of transradial arterial access during coronarography,
      besides pain, means faster patient mobilization and fewer complications. During
      those procedures, vascular sheaths and 5/6 Fr catheters, and lately 4 Fr
      catheters, are used. AIM: To assess the usefulness of 4 Fr catheters and sheaths
      in comparison to 5 Fr in diagnostic coronarography. MATERIAL AND METHODS: In the
      period from 5.12.2010 to 27.02.2012, a group of patients who had coronarography
      with a 4 Fr catheter (n = 20) and a 5 Fr catheter (n = 20) were studied.
      Technical issues and potential problems related to the use of each catheter were
      analyzed. Morphology, biochemical parameters, and local complications were
      analyzed. The assessment included pain intensification during catheter removal
      and insertion in the VAS/numerical (0-10)/verbal scales and the quality of image
      obtained during the coronarography. RESULTS: All the angiograms obtained during
      all the interventions were of diagnostic value and in invasive cardiologists'
      opinions, they did not differ statistically in clarity. Moreover, there were no
      statistically significant differences in radiation/fluoroscopy time, amount of
      contrast medium, or morphological and biochemical parameters. The size of
      hematomas in the 4 Fr group was 17.55 +/-14.6 cm(2), and in the 5 Fr group 31.07
      +/-32.11 cm(2), p = 0.12. The average intensity of pain felt during the
      intervention/at the time of its removal and insertion in the numerical scale was
      in the 4 Fr group 0.65 +/-0.93/0.55 +/-0.94 and in the 5 Fr group 1.88 +/
      1.64/1.42 +/-1.61, p < 0.05. CONCLUSIONS: Application of 4 Fr catheters allows
      one to perform a diagnostic procedure with a small number of local and
      hemorrhagic complications comparable with 5 Fr catheters. Due to reduced pain, it
      is appropriate to continue studies with the use of 4 Fr catheters and sheaths.

PMID- 24570749
TI  - Chronic total occlusion in ostium of right coronary artery - retrograde approach
      as the first-choice method of revascularization?
AB  - Recanalization of chronic total occlusion (CTO) located in the ostium may require
      the operator's ability to use the retrograde approach. We present a case of
      opening a chronically occluded right coronary artery (RCA) by the retrograde
      approach after an unsuccessful attempt of recanalization by classic antegrade
      technique. 

PMID- 24570750
TI  - Distal neuroprotection system as option for right subclavian artery ostial
      recanalization.
AB  - We present the case of a 49-year-old woman with neurological symptoms and severe
      atherosclerosis of aortic arch branches affecting subclavian and carotid
      arteries. Our patient has a history of transient ischemic attack and recurrent
      paresthesias of her right arm. We present a double access intervention using a
      distal embolic neuroprotection device during ostial right subclavian artery
      recanalization. We recommend that use of an embolic protection device in right
      subclavian artery ostial recanalization should be considered. 

PMID- 24570751
TI  - Relationship between SYNTAX score and Trans-Atlantic Inter-Society Consensus II
      classification in patients undergoing diagnostic angiography.
AB  - INTRODUCTION: Peripheral artery disease (PAD) is a marker of systemic
      atherosclerosis and most patients with PAD also have concomitant coronary artery
      disease (CAD). AIM: There are no published data investigating the relationship
      between PAD and CAD complexity assessed by a well-accepted classification system
      such as the SYNTAX score (SS) or Trans-Atlantic Inter-Society Consensus II (TASC
      II). MATERIAL AND METHODS: The study population consisted of 72 patients who
      underwent coronary angiography for the assessment of CAD. At the same session,
      peripheral angiography was performed in cases of suspected PAD. A coronary lesion
      was defined as significant if it caused a 50% reduction of the luminal diameter
      by visual estimation in vessels >= 1.5 mm. The SYNTAX score was computed by
      dedicated software. RESULTS: Patients with peripheral artery disease were divided
      into four groups according to the Trans-Atlantic Inter-Society Consensus II
      classification. Numbers of patients with peripheral artery disease classified as
      A, B, C, and D by the Trans-Atlantic Inter-Society Consensus II classification
      were 27, 16, 18 and 11, respectively. SYNTAX scores for each group from A to D
      were 10 +/-9, 11 +/-10, 24 +/-13 and 27 +/-12, respectively; p for trend < 0.001.
      CONCLUSIONS: Higher Trans-Atlantic Inter-Society Consensus II classification is
      associated with higher SYNTAX score in patients who underwent coronary and
      peripheral diagnostic angiography. It may suggest that arterial atherosclerotic
      disease complexity is a systemic panvascular phenomenon.

PMID- 24570752
TI  - New oral anticoagulants - will they be used with antiplatelet drugs in patients
      with atrial fibrillation after acute coronary syndrome?
AB  - Atrial fibrillation (AF) is the most frequent indication for oral
      anticoagulation. Dual antiplatelet treatment with aspirin and clopidogrel is an
      antithrombotic treatment recommended after acute coronary syndrome and/or
      coronary artery stenting. The evidence for optimal antiplatelet therapy for
      patients who underwent a long-term treatment based on oral anticoagulation is
      strong. A direct thrombin inhibitor, dabigatran, as well as direct factor X
      inhibitors, apixaban and rivaroxaban, are now being commonly used in the
      prevention of thromboembolic complications of AF. Given the consistent increase
      in bleeding and the less consistent reduction in ischaemic events, the overall
      profile of adding new oral anticoagulants to antiplatelet treatment after acute
      coronary syndrome is unknown. 

PMID- 24570753
TI  - Radial artery occlusion after percutaneous coronary interventions - an
      underestimated issue.
AB  - The femoral approach is the most common arterial access for percutaneous coronary
      artery interventions. Despite the convenience and simplicity of this approach, it
      is burdened with a high risk of arterial puncture bleeding, which worsens the
      prognosis of the patient. An alternative approach through the radial artery has
      been gaining more and more popularity in recent years. This is due to a
      significant reduction of local bleeding complications as compared with the
      femoral artery approach. The use of the radial approach in patients with ST
      segment elevation myocardial infarction improves outcome, reducing the risk of
      death, subsequent myocardial infarction and stroke, and is the preferred approach
      according to the latest ESC guidelines. In addition to improving safety, it is
      beneficial for improving patient comfort, with a shorter recovery after the
      procedure, shorter hospitalization and lower medical costs. One of the major
      complications of procedures performed through the radial approach is radial
      artery occlusion (RAO). Although it usually has an asymptomatic course, RAO
      eliminates the ability to use the radial artery as an access in the future. A
      number of factors that contribute to the occurrence of RAO have been identified,
      such as the size of the sheath and the catheter, diameter ratio of the sheath to
      the diameter of the radial artery, insufficient anticoagulation and, above all,
      the way of obtaining hemostasis at the puncture site: the duration of artery
      compression after sheath removal and the preservation of artery patency during
      compression (so-called patent hemostasis). This paper presents the current state
      of the art about the factors that contribute to the occurrence of RAO and methods
      for preventing this complication. 

PMID- 24570754
TI  - Renal denervation - current evidence and perspectives.
AB  - Clinical trials have demonstrated that catheter-based renal denervation (RDN)
      reduces blood pressure and improves blood pressure control in patients with
      resistant hypertension. The follow-up data indicate that the blood pressure
      lowering effect of the procedure may last for up to 36 months. Despite the fact
      that RDN is a growing and promising technique, still more data from clinical
      trials are needed to support the long-term safety and persistent efficacy of this
      approach as compared to the best possible pharmacological treatment. It would
      also be particularly important to recognize the clinical features of patients who
      would benefit most from RDN as well as the clinical characteristics of non
      responders to the procedure. As renal denervation also reduces whole-body
      sympathetic nerve activity, the clinical entities characterized by sympathetic
      nervous system activation - including hypertension coexisting with metabolic
      abnormalities and/or sleep apnea, chronic kidney disease, heart failure, and
      arrhythmias - may be potential new indications for the procedure. However, only a
      few small clinical studies so far have shown the potential benefit of renal
      denervation in these clinical situations and large clinical trials are needed to
      prove this concept. Catheter-based RDN is a promising (but also novel)
      therapeutic approach and further studies should also verify whether it can be
      considered as a procedure in management of patients not only with resistant
      hypertension, but also as a tool in the treatment of mild to moderate forms of
      hypertension. 

PMID- 24570755
TI  - Successful treatment of a young woman with acute complicated myocardial
      infarction.
AB  - Therapeutic hypothermia is method used to improve the neurological status of
      patients who are at risk of ischaemia after myocardial infarction. We report a
      case of a 28-year-old woman who suffered acute myocardial infarction complicated
      by ventricular fibrillation. The patient was successfully resuscitated. Invasive
      and non-invasive medical treatment was applied including therapeutic hypothermia.
      Success was achieved due to adequate public reaction, fast transportation, blood
      vessel revascularization and application of therapeutic hypothermia. The patient
      was successfully discharged after one week of treatment, and just minor changes
      in heart function were present. 

PMID- 24570756
TI  - Stroke following transcatheter aortic valve implantation. Is neuroprotection
      justified?
AB  - Degenerative aortic stenosis (AS) is the most frequent type of valvular heart
      disease. In patients with symptomatic AS surgical aortic valve replacement (SAVR)
      is a recommended treatment strategy. Due to a high risk of perioperative
      mortality, up to 30% of patients with AS are considered not suitable for SAVR. In
      the last 10 years dynamic development of transcatheter aortic valve implantation
      (TAVI) has been observed as an alternative to SAVR in patients with AS and high
      risk for surgery. In the two randomized trials published so far and numerous
      registries, stroke and transient ischemic attack still remain serious
      periprocedural complications after TAVI. Because the majority of these episodes
      are driven by microembolization during the procedure, different neuroprotection
      devices were developed and clinically tested. Embrella and SMT are deflector
      devices, using a microporous membrane mounted on a nitinol frame, designed to
      cover the ostia of the brachiocephalic trunk and the left carotid artery. The
      Claret System is designed to filter cerebral blood flow within the ostia of the
      brachiocephalic trunk, as well as in the left common carotid artery. Randomized
      clinical data have demonstrated that TAVI is associated with more neurological
      events compared to SAVR. However, to date the efficacy of the neuroprotection
      systems has not been assessed in randomized trials. Before we know the results of
      such trials, the use of the devices should be limited to patients at high risk of
      neurological complications, such as patients with previous stroke, massive
      calcification on aortic leaflets, annulus and porcelain aorta. 

PMID- 24570757
TI  - Percutaneous treatment of mitral regurgitation with MitraClip device.
AB  - The percutaneous edge-to-edge repair of mitral regurgitation with a MitraClip
      device has been recently approved in Europe. The results of the randomized
      EVEREST II study showed a favourable safety profile of the technique. However,
      the efficacy in terms of regurgitation reduction in a population with
      predominantly degenerative mitral disease was inferior as compared to the results
      of conventional open heart surgery. Nevertheless, up to 50% of symptomatic heart
      failure patients with severe mainly functional mitral regurgitation are not
      treated surgically because of very high procedural risk. The registry data
      suggest that the minimally invasive and generally well-tolerated MitraClip
      procedure reduces symptoms and need for recurrent hospitalization and improves
      left ventricular function in inoperable subjects. The ongoing randomized clinical
      trials with clinical endpoints will further define the current role of
      percutaneous edge-to-edge repair in heart failure patients with mitral
      regurgitation. 

PMID- 24570758
TI  - Transcatheter closure of sinus of Valsalva aneurysm rupture in a young patient.
AB  - Sinus of Valsalva aneurysm rupture is a rare cardiac anomaly and demands prompt
      treatment. We present a case of a young patient who underwent transcatheter
      closure due to a ruptured sinus of Valsalva aneurysm. 

PMID- 24570759
TI  - Coronary accordion effect mimicking coronary dissection.
AB  - The coronary "accordion" effect is a rare pseudo-complication of percutaneous
      coronary intervention (PCI). It is usually observed due to straightening and
      shortening of tortuous vessels with stiff guidewires during PCI. In this case
      report, we present an interesting case of the coronary accordion effect observed
      in a 52-year-old woman undergoing PCI. 

PMID- 24570760
TI  - Cardiac arrest during percutaneous coronary intervention in a patient 'resistant'
      to clopidogrel - successful 50-minute mechanical chest compression.
AB  - We report a case of 72-year-old female patient with end-stage chronic kidney
      disease, undergoing percutaneous coronary intervention (PCI) that resulted in a
      cardiac arrest caused by a thrombus mediated flow limitation in the left coronary
      artery. With mechanical cardiopulmonary resuscitation (CPR) PCI of the left main
      artery was performed successfully during 50 min cardiac arrest. The patient was
      discharged from the hospital without compromising cardiac function and
      neurological deficits. 

PMID- 24570761
TI  - Coronary artery perforation treated with multiple bare metal stent implantation.
AB  - Although coronary artery perforations are quite rare, when they occur, the
      consequences are devastating. Treatment options differ according to the type,
      location and severity of the perforation. As a general rule severe perforations
      are treated with covered stents. However, when implanting a covered stent is not
      an option as in our case due to various reasons, multiple bare metal stent
      implantation may be a good option. Besides that, management of the antiplatelet
      and the anticoagulant therapy remains controversial. We believe that therapy
      should be individualized. 

PMID- 24570762
TI  - Speckle-free laser imaging using random laser illumination.

PMID- 24570764
TI  - Inspiratory Flows and Volumes in Subjects with Non-CF Bronchiectasis Using a New
      Dry Powder Inhaler Device.
AB  - INTRODUCTION: Drug inhalation via a dry-powder inhaler (DPI) is a convenient,
      time efficient alternative to nebulizers in the treatment of cystic fibrosis (CF)
      or non-CF bronchiectasis. Efficient drug administration via DPIs depends on the
      device resistance and adequate (>=45L/min) inspiratory flows and volumes
      generated by individuals. Drypowder mannitol is delivered using a RS01 breath
      actuated device developed by Plastiape, for Pharmaxis. The study aim was to
      determine in vivo if non-CF bronchiectasis patients' inspiratory flows and
      volumes are adequate to use the RS01 DPI device. MATERIALS AND METHODOLOGY: An
      open, non-interventional study; enrolled 17 subjects with non-CF bronchiectasis,
      18 to 80 years, with baseline FEV1 >=1.0L and >=500/00 predicted. Inspiratory
      flows and volumes were measured when subjects inhaled in a controlled manner
      through the RS01 device in series with a spirometer. RESULTS: The mean
      inspiratory volume (IV) of non-CF bronchiectasis subjects was 2.08 +/- 0.5L and
      achieved a mean PIF of 78.6 +/- 11.2L/min with the inhaler device. CONCLUSION:
      Use of the RS01 DPI device allowed adequate inspiratory flow and volume for
      dispersion of dry-powder mannitol in non-CF bronchiectasis patients.

PMID- 24570763
TI  - Inspiratory flows and volumes in subjects with cystic fibrosis using a new dry
      powder inhaler device.
AB  - INTRODUCTION: Drug inhalation via a dry-powder inhaler (DPI) is a convenient,
      time efficient alternative to nebulizers in the treatment of cystic fibrosis
      (CF). Efficient drug administration via DPIs depends on the device resistance and
      adequate (>= 45L/min) inspiratory flows and volumes generated by individuals. Dry
      powder mannitol is delivered using a RS01 breath-actuated device developed by
      Plastiape, for Pharmaxis. The study aim was to determine in vivo if CF patients'
      inspiratory flows and volumes are adequate to use the RS01 DPI device. MATERIALS
      AND METHODOLOGY: An open, non-interventional study; enrolled 25 CF subjects, aged
      >= 6 years with FEV1 >= 30 to < 900/00 predicted. Inspiratory flows and volumes
      were measured when subjects inhaled in a controlled manner through the RS01
      device in series with a spirometer. RESULTS: The mean inspiratory volume (IV) of
      CF subjects was 1.83L +/- 0.97. Their achieved mean +/- SD peak inspiratory flow
      (PIF) was 75.5 +/- 27.2L/min. Twenty-three subjects (92%) achieved PIF of >
      45L/min with the inhaler device; eighteen of those subjects (78%) had a baseline
      FEV1 of > 1L. CONCLUSION: Use of the RS01 DPI device allowed adequate inspiratory
      flow and volume for dispersion of dry-powder mannitol in CF patients.

PMID- 24570765
TI  - CASE REPORT Treatment of a Lower Extremity Lymphocele With Intraoperative
      Lymphatic Mapping.
AB  - OBJECTIVE: Lower extremity lymphoceles secondary to saphenous vein grafting are
      exceptionally rare and there is only 1 previously reported case in the English
      literature. Data on treatment of lower extremity lymphoceles are limited and
      based on studies of groin lymphoceles. We discuss operative resection with
      selective ligation of feeding lymphatic vessels as a treatment option of lower
      extremity lymphoceles. METHODS: A 64-year-old man who had undergone coronary
      artery bypass grafting 6 years prior presented with a left lower extremity mass
      at the site where his saphenous vein had been harvested. Examination demonstrated
      a 12-cm, mobile, nonpulsatile mass at his medial left calf. The findings of
      magnetic resonance imaging were consistent with a lymphocele. RESULTS:
      Intraoperative injection of isosulfan blue dye was used to identify feeding
      lymphatic vessels and the lymphocele cavity was excised. Leg drains were
      discontinued after 3 days, and the patient was discharged home after 6 days.
      CONCLUSION: Operative resection with isosulfan blue dye lymphatic mapping and
      selective ligation of lymphatic vessels is a viable treatment of lower extremity
      lymphoceles.

PMID- 24570766
TI  - Ovine forestomach matrix as a substrate for single-stage split-thickness graft
      reconstruction.
AB  - OBJECTIVE: Split skin graft reconstruction of scalp defects often leaves an
      obvious contour defect. Here, we aimed to demonstrate the use of a decellularized
      extracellular matrix biomaterial, termed ovine forestomach matrix (OFM), as a
      substrate for split-thickness skin grafts (STSGs) for scalp reconstruction.
      METHODS: Following full-thickness tumor excision, OFM was applied directly to
      skull periosteum, and then an STSG was applied. Participants were monitored for
      graft take, epithelialization, and cosmetic outcomes. RESULTS: Participants
      responded well to the procedure with more than 95% graft take in 4 participants,
      and 100% epithelialization of the grafts after 2 weeks. A 30% graft take was
      observed in the fifth participant due to local infection and partial necrosis of
      the graft. Ovine forestomach matrix was remodelled with time and the regenerated
      dermis was well vascularized and had robust and ordered collagen deposition.
      CONCLUSIONS: This series demonstrates that OFM can serve as a temporary dermal
      scaffold to support an overlying STSG and allow for a single-stage grafting
      procedure.

PMID- 24570767
TI  - Isolated subcutaneous mass of the scalp as initial presentation of metastatic
      squamous cell carcinoma of the lung.

PMID- 24570769
TI  - A simple and safe technique for manipulation of retrosternal dissection in the
      nuss procedure.
AB  - OBJECTIVE: The Nuss procedure has become the first choice for repairing the
      pectus excavatum because of the advantages of the technique including minimal
      invasiveness and short operative duration. Although this technique appears simple
      and easy, life-threatening complications during dissection such as intraoperative
      cardiac perforation have been reported. We developed a new approach for safer
      dissection of retrosternal space. METHODS: We use a dissector that is commonly
      used for laparoscopic operation, instead of the Nuss introducer. The dissector
      goes through the same skin incision where the Nuss bar will be inserted. The
      major difference is the position of dissector insertion, which is set up more
      dorsally than usual, and the use of a laparoscopic dissector instead of the Nuss
      introducer. In this new approach, the direction of dissection is from dorsal
      toward the anterior thoracic wall, which allows us to visually follow the tip of
      the dissector throughout the surgery. Moreover using the dissector that has
      better manipulation capability enables us the fine dissection and also is able to
      precisely determine both the layer and the area of the dissection level. RESULTS:
      We have treated more than 150 patients using this technique without any
      complications since 2008. In all the cases, safer dissection of the retrosternal
      space was performed with good results. CONCLUSION: We believe every surgeon can
      easily apply this procedure to patients with pectus excavatum, and this procedure
      can reduce the stress during the dissection.

PMID- 24570768
TI  - Comparative host response of 2 human acellular dermal matrices in a primate
      implant model.
AB  - OBJECTIVE: We examined the differences in capsule formation between 2
      commercially available human acellular dermal matrices in a nonhuman primate
      model. METHODS: Primates were implanted dorsally with a subcutaneously placed
      tissue expander and randomized into 3 groups, receiving skin coverage only,
      coverage with non-irradiated freeze-dried human acellular dermal matrix, or
      coverage with gamma-irradiated human acellular dermal matrix. After 9 weeks, soft
      tissue around the tissue expander was excised and evaluated qualitatively and
      quantitatively to assess extent of inflammation (CD68 antibodies and interleukin
      6 levels), degradation and fibrosis (matrix metalloproteinase-1 and procollagen-1
      staining), and mechanical (tensile) strength. RESULTS: Histological evaluation of
      tissue around the tissue expander indicated differences in host response,
      suggesting capsule presence in the gamma-irradiated matrix group but not the
      freeze-dried matrix group. The extent of local inflammation was much higher in
      the gamma-irradiated matrix group which demonstrated mean (standard deviation)
      localized interleukin-6 concentration of 67.3 (53.6) vs 16.3 (6.7) pg/mg protein
      in the non-irradiated matrix group. There was robust degradation and fibrotic
      response in the gamma-irradiated matrix group versus the freeze-dried matrix
      group. Mechanical testing indicated mean (standard deviation) ultimate tensile
      strength of 12.0 (7.1) N in the gamma-irradiated matrix group versus 99.3 (48.8)
      N in the freeze-dried matrix group. CONCLUSIONS: Enclosure of a tissue expander
      with human acellular dermal matrix untreated by gamma irradiation led to minimal
      inflammation and minimal evidence of fibrosis/capsule around the tissue expander
      compared with robust capsule formation around the tissue expander that was
      covered by a gamma-irradiated human acellular dermal matrix.

PMID- 24570770
TI  - Anatomic Evaluation of the Internal Mammary Vessels Using Multidetector CT
      Angiography Images in 100 Asian Patients.

PMID- 24570771
TI  - Posterior interosseous nerve compression.

PMID- 24570772
TI  - [Unilateral coloboma of the eye lens: about a case].

PMID- 24570774
TI  - [Oculocutaneous albinism: iris in transillumination].

PMID- 24570773
TI  - [Prostate laser photovaporisation in patients at high risk of bleeding].

PMID- 24570775
TI  - Cerebral venous sinus thrombosis in HIV-infected patients: report of 2 cases.
AB  - Infection with the human immunodeficiency virus (HIV) is associated with
      increased risk of cerebrovascular disease; however Cerebral Venous Sinus
      Thrombosis (CVST) is rarely associated with HIV-related cerebrovascular events.
      We describe two cases of HIV-positive patients who, at the same time, presented
      to our hospital with deep cerebral venous thrombosis and stroke. 

PMID- 24570776
TI  - A rare third ventricle solitary tuberculoma.
AB  - The localization of the tuberculoma at the third ventricle is rare. The authors
      report a case of third ventricle solitary Tuberculoma which has occurred in a 10
      year old patient and revealed by a syndrome of intracranial hypertension without
      tuberculosis stigma. This lesion appears clinically and radiologically as a
      primary brain tumor. A total removal using a subchoroidal approach to the third
      ventricle has been performed. Histological examination showed a tuberculous like
      granuloma. An adjuvant antituberculous chemotherapy practiced for 6 months
      brought the complete cure. The authors insist on the diagnostic and therapeutic
      difficulties in front of a third ventricle solitary tuberculoma. 

PMID- 24570777
TI  - [Othello syndrome: a case observed in Ouagadougou].

PMID- 24570779
TI  - [Atypical zoster in an immunocompromised patient].

PMID- 24570778
TI  - Sero-prevalence of hepatitis B virus and hepatitis C virus among HIV patients in
      a suburban University Teaching Hospital in South-East Nigeria.
AB  - INTRODUCTION: Highly active antiretroviral therapy (HAART) has improved survival
      of human immunodeficiency virus (HIV) patients. Concurrent morbidities from liver
      diseases among these patients have also been observed due to co-infection with
      hepatitis B and C viruses (HBV and HCV). HAART reduces liver-associated
      morbidities and mortalities in such patients. Unfortunately free testing of HBV
      and HCV are not provided alongside free HIV testing and treatment in Nigeria. We
      assessed the seroprevalence of HBV and HCV among HIV patients presenting for
      treatment in our center. METHODS: This prospective study of adult patients with
      HIV/AIDS assessed the seroprevalence of HBV and HCV co-infection using a 19-item
      questionnaire and collection of 2ml venous blood for hepatitis B surface antigens
      (HBsAg) and anti-HCV antibodies. All previously diagnosed HIV patients of the
      unit were excluded from the study. RESULTS: Of the 404 patients, 69.2% were
      females while 30.8% were males. Married participants were 59.6%, 25.3% were
      single and 15% were previously married. A large proportion (69%) of patients were
      farmers, artisans and traders. Most had some formal education; secondary (55.3%),
      primary 27.3%, tertiary 13.8%. HBsAg positive participants were 9 (2.2%) while 3
      (0.7%) were positive for HCV. No participant had triple infection of HIV/HBV/HCV.
      CONCLUSION: Seroprevalence of HBV and HCV is low among HIV patients in Orlu.
      However there is a need for HBV and HCV testing of all HIV positive patients to
      reduce morbidities and mortalities from liver diseases.

PMID- 24570780
TI  - [Conservative management of postpartum hematomas large volume: about 3 cases].

PMID- 24570781
TI  - Research priority setting for health policy and health systems strengthening in
      Nigeria: the policymakers and stakeholders perspective and involvement.
AB  - INTRODUCTION: Nigeria is one of the low and middle income countries (LMICs)
      facing severe resource constraint, making it impossible for adequate resources to
      be allocated to the health sector. Priority setting becomes imperative because it
      guides investments in health care, health research and respects resource
      constraints. The objective of this study was to enhance the knowledge and
      understanding of policymakers on research priority setting and to conduct a
      research priority setting exercise. METHODS: A one-day evidence-to-policy
      research priority setting meeting was held. The meeting participants included
      senior and middle level policymakers and key decision makers/stakeholders in the
      health sector in Ebonyi State southeastern Nigeria. The priorities setting
      meeting involved a training session on priority setting process and conduction of
      priority setting exercise using the essential national health research (ENHR)
      approach. The focus was on the health systems building blocks (health workforce;
      health finance; leadership/governance; medical products/technology; service
      delivery; and health information/evidence). RESULTS: Of the total of 92
      policymakers invited 90(97.8%) attended the meeting. It was the consensus of the
      policymakers that research should focus on the challenges of optimal access to
      health products and technology; effective health service delivery and disease
      control under a national emergency situation; the shortfalls in the supply of
      professional personnel; and the issues of governance in the health sector
      management. CONCLUSION: Research priority setting exercise involving policymakers
      is an example of demand driven strategy in the health policymaking process
      capable of reversing inequities and strengthening the health systems in LMICs.

PMID- 24570783
TI  - Morphea on the breast and pregnancy.

PMID- 24570782
TI  - Multiple myeloma revealed by spinal cord compression and herpes zoster in a 36
      year-old Cameroonian.
AB  - Multiple myeloma is a malignant plasma cell disorder occurring mostly in people
      above 60 years old. The authors describe a case of multiple myeloma in a 36-year
      old patient revealed by spinal cord compression and Herpes zoster with a rapidly
      unfavourable outcome. 

PMID- 24570784
TI  - [Phospho-calcic status in chronic hemodialysis in Oriental Morocco: assessment of
      adherence to K/DOQI and KDIGO recommendations].

PMID- 24570785
TI  - [Bartonella endocarditis in Tunisia: lesional and evolutionary characteristics].

PMID- 24570786
TI  - [Dermatozoic delirium: about a case].

PMID- 24570788
TI  - Cervical hibernoma in a two year old boy.
AB  - Hibernomas are uncommon benign soft tissue tumours mimicking brown fat. They are
      mostly seen in the fourth and fifth decades of life. Only few cases in the
      cervical area have been reported. Because of its rarity in pediatrics and
      difficult diagnosis, we report a tow year-old patient with a cervical tumor.
      Ultrasound and computed tomography exams showed an infiltrative, with
      hypervascular and lipomatous features. After tumor excision, histopathological
      exam confirmed the diagnosis of hibernoma or brown fat tumor. This presentation
      describes the characteristics of this type of tumor, rare in children.

PMID- 24570787
TI  - [About a case of very prolonged abdominal pregnancy].

PMID- 24570789
TI  - An unusual cause of meningismus.

PMID- 24570790
TI  - [Gumma of the face revealing a late congenital syphilis].

PMID- 24570793
TI  - [Abscess of the thigh: think of tuberculosis].

PMID- 24570792
TI  - Cancer incidence in Morocco: report from Casablanca registry 2005-2007.
AB  - INTRODUCTION: Few population-based cancer registries are in place in developing
      countries. In order to know the burden of cancer in Moroccan population, cancer
      registry initiative was put in place in the Casablanca district, the biggest city
      of Morocco. METHODS: The data collected covers 3.6 millions inhabitant and
      included Casablanca city and the administrative region. RESULTS: The data
      collected in the years 2005-07 show that the top 5 forms of cancers in women were
      breast (ASR: 36.4 per 100,000), cervical (15.0), thyroid (6.7), colon-rectum
      (5.8), and ovarian (5.3); the top 5 cancers in men were lung (25.9), prostate
      (13.5), bladder (8.7), colon-rectum (8.1) and non-Hodgkin lymphoma (7.2). Tumours
      of haematopoietic and lymphoid tissues represented 11% of all cancers (skin
      excluded); some presented unusual sex ratios. For breast, cervical, colorectal
      and thyroid cancer, respectively 57%, 42%, 28% and 60% of the cases were under 50
      years of age. This was attributable to particularly low numbers of cases recorded
      among old people, and the young age of the general population; the observed age
      specific incidences under age 50 were not higher than in western countries.
      Cancers at young ages were particularly common in women: 67% of the cases were
      under 50. Stage at diagnosis could be obtained for 82% of the breast cancer cases
      and was as follows: 28% local, 63% regional and 9% distant, in the absence of
      screening. CONCLUSION: These first population-based data have provided an
      invaluable resource for the national cancer control plan of Morocco, and will be
      useful tool to its future evaluation.

PMID- 24570791
TI  - Factors influencing adherence to paediatric antiretroviral therapy in
      Portharcourt, South- South Nigeria.
AB  - INTRODUCTION: The efficiency of antiretroviral therapy (ART) depends on a near
      perfect level of patient's adherence. Adherence in children poses peculiar
      challenges. The aim of the study was to determine the adherence level and factors
      influencing adherence among HIV-infected children and adolescents in University
      of Port Harcourt Teaching Hospital, Nigeria. METHODS: A cross-sectional survey of
      HIV-infected children and adolescents on ART using self-report by the
      caregiver/child in the past one month. RESULTS: A total of 213 caregivers and
      their children were interviewed. A hundred and sixty-two (76.1%) had adherence
      rates >=95%. Only 126 (59.2%) were completely (100%) adherent. The commonest
      caregiver-related factors for missing doses were forgetfulness 48(55.2%),
      travelled 22(25.3%) and drugs finished 16(18.4%), while the child-related factors
      were refused drugs 10(11.5%), slept 8(9.2%), and vomited 8(9.2%). Sixty-eight
      (31.9%) caregivers reported missing clinic visit and reasons given were travelled
      18(26.5%), caregiver ill 12(17.6%) and family problems 9(13.2%). Predictors of
      poor adherence include mother as the primary caregiver (OR 3.32; 95%CI, 1.33
      8.67), younger than 5 years (OR 2.62; 95%CI, 1.30-5.31) and presence of a co
      morbidity (OR 3.97; 95%CI, 1.92-8.33). Having a medication reminder strategy (OR
      6.34; 95%CI, 3.04-13.31), regular clinic visits (OR 8.55; 95%CI 4.01-18.45) and
      status disclosure (p = 0.008) predicted a better adherence. The caregiver's age
      (p= 0.11), education (p = 0.86), socioeconomic status (p = 0.89), gender of the
      child (p = 0.84), type of ART (p = 0.2) and duration of ART (1.0) did not
      significantly affect adherence. CONCLUSION: Adherence is still suboptimal. Since
      barriers to Paediatric ART adherence are largely caregiver-dependent, identifying
      and addressing these barriers in each caregiver-child pair will improve adherence
      and patient outcome.

PMID- 24570794
TI  - Complete acute uterine inversion.

PMID- 24570795
TI  - Improved services to enrollees into an HIV rural care and treatment center in
      Tanzania.
AB  - Better quality of services is essential for the sustainability of HIV programs,
      in particular in rural Sub-Saharan Africa, to support the increasing number of
      individuals treated with combination antiretroviral therapy (cART). However,
      longitudinal data from rural care and treatment centers (CTC) are scarce. The
      objective was to assess trend in quality of care for HIV infected persons before
      start of combination antiretroviral therapy (pre-ART). A retrospective analysis
      of pre-ART registers and patient's files of 1950 patients enrolled in the
      Bagamoyo CTC in Tanzania between 2008 and 2010 analyzing was conducted; with
      parameters including year of enrollment, gender, age, CD4 cell count and WHO
      clinical stage at time enrollment. We noted a significant increase by 20% of
      total patients who had CD4 cell count performed from 69% (n=457) in 2008, 83%
      (n=493) 2009 to 89% (n=616) 2010 (X(2)= 87.014, P(2)= 14.945, P(2)= 85.028, P(3).
      Efforts must be undertaken for more HIV testing and timely referral of HIV
      infected patients to CTC. 

PMID- 24570796
TI  - [Metaplastic breast carcinoma with extensive bone differentiation: report of a
      case].

PMID- 24570797
TI  - Characterization and factors associated with diarrhoeal diseases caused by
      enteric bacterial pathogens among children aged five years and below attending
      Igembe District Hospital, Kenya.
AB  - INTRODUCTION: Diarrhoea remains a major public health problem in East African
      nations such as Kenya. Surveillance for a broad range of enteric pathogens is
      necessary to accurately predict the frequency of pathogens and potential changes
      in antibiotic resistance patterns. METHODS: A cross sectional study was conducted
      in Igembe District Hospital in Meru County to determine the burden and factors
      associated enteric bacterial infection among children aged five years and below.
      Stool samples were collected between March and July 2012. Bacterial pathogens
      were identified and antibiotic susceptibility of bacterial isolates was
      ascertained. Questionnaire was administered to the 308 study participants to
      identify the modifiable risk factors. Data was entered and analyzed using Epi
      Info version 3.5.3. RESULTS: The study recruited 308 children. The mean age was
      27.25 months, median of 26.0 months and age range between 2-60 months. The
      bacterial isolation rates were ETEC 9.1%, EPEC 6.8% and EAEC 12.3%, Salmonella
      paratyphoid (10.4%), Shigella flexineri (1.9%) and Shigella dysentriae (0.9%).
      Over 95%, of the isolates were resistance to amoxicillin, sulphinatozole,
      cotrimoxazole. Six factors were independently associated with diarrhoeal
      diseases, occupation of the parent/ guardian (miraa business) (OR=1.8, CI:1.44
      4.99),care taker not washing hands after changing napkins (OR= 1.6, CI:1.2-19.7),
      child drank untreated water from the river (OR= 2.7, CI:2.4-9.9) child not
      exclusively breastfed (OR= 2.4, CI:2.1-10.5),child did not Wash hands before
      eating (OR=2.2, CI:1.91-16.3) and after visiting toilet (OR=3.7,CI:2.8-39.4).
      Eating of mangoes was found to be protective against diarrhoea (OR=0.5, CI:0.03
      0.89). CONCLUSION: The bacterial pathogens were found to be a significant cause
      of diarrhoea in the study participants. We established higher resistance to
      several commonly prescribed antibiotics. Several factors were significantly
      association with diarrhoea illness. We recommend multifaceted approach that
      acknowledges the public health aspects that would reduce the burden of diarrhoea
      infections as identified in this study.

PMID- 24570799
TI  - [Characteristics of TB patients in west Cameroon: 2000-2009].

PMID- 24570798
TI  - Status report on hypertension in Africa--consultative review for the 6th Session
      of the African Union Conference of Ministers of Health on NCD's.
AB  - Hypertension has always been regarded as a disease of affluence but this has
      changed drastically in the last two decades with average blood pressures now
      higher in Africa than in Europe and USA and the prevalence increasing among poor
      sections of society. We have conducted a literature search on PubMed on a broad
      range of topics regarding hypertension in Africa, including data collection from
      related documents from World Health Organization and other relevant organizations
      that are available in this field. We have shared the initial results and drafts
      with international specialists in the context of hypertension in Africa and
      incorporated their feedback. Hypertension is the number one risk factor for CVD
      in Africa. Consequently, cardiovascular disease (CVD) has taken over as number
      one cause of death in Africa and the total numbers will further increase in the
      next decades reflecting on the growing urbanization and related lifestyle
      changes. The new epidemic of hypertension and CVD is not only an important public
      health problem, but it will also have a big economic impact as a significant
      proportion of the productive population becomes chronically ill or die, leaving
      their families in poverty. It is essential to develop and share best practices
      for affordable and effective community-based programs in screening and treatment
      of hypertension. In order to prevent and control hypertension in the population,
      Africa needs policies developed and implemented through a multi-sectoral approach
      involving the Ministries of Health and other sectors including education,
      agriculture, transport, finance among others. 

PMID- 24570800
TI  - [Giant and recalcitrant warts: successful treatment with photodynamic therapy].

PMID- 24570801
TI  - Overview of the development of the Korean exposure factors handbook.
AB  - A set of exposure factors that reflects the characteristics of individual
      behavior capable of influencing exposure is essential for risk and exposure
      assessment. In 2007, the Korean Exposure Factors Handbook was, therefore, issued,
      driven by the need to develop reliable exposure factors representing the Korean
      population. The purpose of this study was to overview the development process of
      the Korean Exposure Factors Handbook and major recommended exposure values for
      the Korean population to allow information exchanges and comparison of
      recommended values among nations. The researchers reviewed the domestic data that
      could be used in the development of exposure factors, confirmed a knowledge gap,
      and set a priority of development by phases. A methodology to measure exposure
      factors was established to develop measuring techniques and test their validity.
      Data were processed or a survey was conducted according to the availability of
      data. The study thus produced recommended values for 24 exposure factors grouped
      by general exposure factors, food ingestion factors, and activity factors by
      setting up a database of exposure factors and carrying out statistical analysis.
      The study has significantly contributed to reducing the potential uncertainty of
      the risk and exposure assessment derived by the application of foreign data or
      research findings lacking representativeness or grounds by developing a set of
      exposure factors reflecting the characteristics of the Korean people. It will be
      necessary to conduct revisions in light of the changing statistical values of
      national data and the exposure factors based on Korean characteristics. 

PMID- 24570802
TI  - General factors of the Korean exposure factors handbook.
AB  - Risk assessment considers the situations and characteristics of the exposure
      environment and host. Various physiological variables of the human body reflects
      the characteristics of the population that can directly influence risk exposure.
      Therefore, identification of exposure factors based on the Korean population is
      required for appropriate risk assessment. It is expected that a handbook about
      general exposure factors will be used by professionals in many fields as well as
      the risk assessors of the health department. The process of developing the
      exposure factors handbook for the Korean population will be introduced in this
      article, with a specific focus on the general exposure factors including life
      expectancy, body weight, surface area, inhalation rates, amount of water intake,
      and soil ingestion targeting the Korean population. The researchers used national
      databases including the Life Table and the 2005 Time Use Survey from the National
      Statistical Office. The anthropometric study of size in Korea used the resources
      provided by the Korean Agency for Technology and Standards. In addition, direct
      measurement and questionnaire surveys of representative samples were performed to
      calculate the inhalation rate, drinking water intake, and soil ingestion. 

PMID- 24570803
TI  - Food ingestion factors of the Korean exposure factors handbook.
AB  - The purpose of this study was to establish food ingestion factors needed to
      assess exposure to contaminants through food ingestion. The study reclassified
      the raw data of the Korean National Health and Nutrition Examination Survey in
      2001 into 12 subcategories including grain products, meat products, fish and
      shellfish, and vegetables for international comparability of exposure evaluation.
      The criteria for food intake calculation were unified according to the
      characteristics of food groups, and recommended values for food ingestion factors
      were calculated through moisture correction and recategorization of cooked,
      processed, and mixed foods for each group. The average intake rate for grain and
      grain products was 6.25 g/kg-d per capita and the men's intake rate was
      approximately 8% higher than that of the women. The average intake rate of meat
      and meat products was 1.62 g/kg-d per capita and the men's intake rate was 30%
      higher than that of the women, on average. The average intake rate of fish and
      shellfish was 1.53 g/kg-d per capita, and the age groups of 1 to 2 and 3 to 6
      recorded higher capita intake rates than other age groups, 2.62 g/kg-d and 2.25
      g/kg-d, respectively. The average intake rate of vegetables was 6.47 g/kg-d per
      capita, with the age group of 1 to 2 recording the highest per capita intake rate
      of 9.79 g/kg-d and that of 13 to 19 recording the lowest mean. The study also
      offers recommended values for food ingestion factors of other food groups by
      gender, age, and region. The food ingestion exposure factors will need future
      updates in consideration of ongoing changes in food consumption behavior. 

PMID- 24570804
TI  - Activity factors of the Korean exposure factors handbook.
AB  - Exposure factors based on the Korean population are required for making
      appropriate risk assessment. It is expected that handbooks for exposure factors
      will be applied in many fields, as well as by health department risk assessors.
      The present article describes the development of an exposure factors handbook
      that specifically focuses on human activities in situations involving the
      possible risk of exposure to environmental contaminants. We define majour
      exposure factors that represent behavioral patterns for risk assessment,
      including time spent on routine activities, in different places, on using
      transportation, and engaged in activities related to water contact including
      swimming, bathing and washing. Duration of residence and employment are also
      defined. National survey data were used to identify recommended levels of
      exposure factors in terms of time spent on routine activities and period of
      residence and employment. An online survey was conducted with 2073 subjects who
      were selected using a stratified random sampling method in order to develop a
      list of exposure factors for the time spent in different places and in performing
      water-related activities. We provide the statistical distribution of the
      variables, and report reference levels of average exposure based on the reliable
      data in our exposure factors handbook. 

PMID- 24570805
TI  - Levothyroxine dose and fracture risk according to the osteoporosis status in
      elderly women.
AB  - OBJECTIVES: To evaluate the association between fracture risk and levothyroxine
      use in elderly women with hypothyroidism, according to previous osteoporosis
      history. METHODS: We conducted a cohort study from the Korean Health Insurance
      Review and Assessment Service claims database from January 2005 to June 2006. The
      study population comprised women aged >=65 years who had been diagnosed with
      hypothyroidism and prescribed levothyroxine monotherapy. We excluded patients who
      met any of the following criteria: previous fracture history, hyperthyroidism,
      thyroid cancer, or pituitary disorder; low levothyroxine adherence; or a follow
      up period <90 days. We categorized the daily levothyroxine doses into 4 groups:
      <=50 ug/d, 51 to 100 ug/d, 101 to 150 ug/d, and >150 ug/d. The hazard ratios
      (HRs) and 95% confidence intervals (CIs) were estimated with the Cox proportional
      hazard model, and subgroup analyses were performed according to the osteoporosis
      history and osteoporosis-specific drug prescription status. RESULTS: Among 11 155
      cohort participants, 35.6% had previous histories of osteoporosis. The adjusted
      HR of fracture for the >150 ug/d group, compared with the 51 to 100 ug/d group,
      was 1.56 (95% CI, 1.03 to 2.37) in osteoporosis subgroup. In the highly probable
      osteoporosis subgroup, restricted to patients who were concurrently prescribed
      osteoporosis-specific drugs, the adjusted HR of fracture for the >150 ug/d group,
      compared with the 51 to 100 ug/d group, was 1.93 (95% CI, 1.14 to 3.26).
      CONCLUSIONS: While further studies are needed, physicians should be concerned
      about potential levothyroxine overtreatment in elderly osteoporosis patients.

PMID- 24570806
TI  - Implementation and results of a survey on safe community programs in Gangbuk-gu,
      Korea: focusing on participants at a local public health center.
AB  - OBJECTIVES: The purpose of this study was to investigate the current status of
      and problems with the Safe Community Programs in Gangbuk-gu, one of the 25
      districts of the capital city of Korea. METHODS: The study subjects were 396
      individuals who were involved in Safe Community Programs between 2009 and 2011.
      We examined the effectiveness and willingness of respondents to participate as a
      safety leader of the Safe Community Program with a questionnaire. We examined the
      injury death rates of Gangbuk-gu by using of the death certificate data of
      Korea's National Statistical Office. Descriptive statistics and chi-squared tests
      were used. RESULTS: The effectiveness of programs did not differ but active
      participation differed significantly among subjects (p<0.05). The injury death
      rate of Gangbuk-gu as a whole increased during the implementation period.
      However, senior safety, in particular, may be a helpful program for reducing
      injuries in Gangbuk-gu. CONCLUSIONS: This study suggests that the lack of active
      participation may be a major problem of Safe Community Programs in Gangbuk-gu.
      Therefore, Safe Community Programs should be expanded to the entire district of
      Gangbuk-gu and more active participation programs should be developed.

PMID- 24570808
TI  - Factors predicting the physical activity behavior of female adolescents: a test
      of the health promotion model.
AB  - OBJECTIVES: Physical activity behavior begins to decline during adolescence and
      continues to decrease throughout young adulthood. This study aims to explain
      factors that influence physical activity behavior in a sample of female
      adolescents using a health promotion model framework. METHODS: This cross
      sectional survey was used to explore physical activity behavior among a sample of
      female adolescents. Participants completed measures of physical activity,
      perceived self-efficacy, self-esteem, social support, perceived barriers, and
      perceived affect. Interactions among the variables were examined using path
      analysis within a covariance modeling framework. RESULTS: The final model
      accounted for an R(2) value of 0.52 for physical activity and offered a good
      model-data fit. The results indicated that physical activity was predicted by
      self-esteem (beta=0.46, p<0.001), perceived self-efficacy (beta=0.40, p<0.001),
      social support (beta=0.24, p<0.001), perceived barriers (beta=-0.19, p<0.001),
      and perceived affect (beta=0.17, p<0.001). CONCLUSIONS: The findings of this
      study showed that the health promotion model was useful to predict physical
      activity behavior among the Iranian female adolescents. Information related to
      the predictors of physical activity behavior will help researchers plan more
      tailored culturally relevant health promotion interventions for this population.

PMID- 24570807
TI  - IL-4 and IL-5 secretions predominate in the airways of wistar rats exposed to
      toluene diisocyanate vapor.
AB  - OBJECTIVES: We established a Wistar rat model of asthma caused by toluene
      diisocyanate (TDI) exposure, and investigated the relationship between TDI
      exposure concentrations and respiratory hypersensitivity, airway inflammation,
      and cytokine secretions in animals, to better understand the mechanism of TDI
      induced occupational asthma. METHODS: Wistar rats were exposed to two different
      concentrations of TDI vapor four hours a day for five consecutive days.
      Bronchoalveolar lavage (BAL) was performed, and differential leucocytes from the
      BAL fluid were analyzed. Lung histopathological examination was carried out to
      investigate the inflammatory status in the airways. Production of cytokines
      interleukin (IL)-4 and IL-5 productions in the BAL fluid in vivo was determined
      with enzyme-linked immunosorbent assay kits. RESULTS: The TDI-exposed rats
      exhibited greater airway hypersensitivity symptoms than the control rats. The BAL
      differential cell count and lung histopathological examination demonstrated that
      inflammation reactions were present in both the central and peripheral airways,
      characterized with marked infiltration of eosinophils in the TDI-exposed rats.
      The cytokine assay showed that IL-4 and IL-5 were predominantly produced in the
      BAL fluid in vivo. CONCLUSIONS: These findings imply that TDI exposure
      concentrations may greatly affect the occurrence and extent of inflammatory
      events and that Th2 type cytokines may play an important role in the
      immunopathogenesis of TDI-induced occupational respiratory hypersensitivity.

PMID- 24570810
TI  - Mortality and real cause of death from the nonlesional intracerebral hemorrhage.
AB  - OBJECTIVE: The case fatality rate of nonlesional intracerebral hemorrhage (n-ICH)
      was high and not changed. Knowing the causes is important to their prevention;
      however, the reasons have not been studied. The aims of this study were to
      determine the cause of death, to improve the clinical outcomes. METHODS: We
      retrospectively analyzed consecutive cases of nonlesional intracerebral
      hemorrhage in a prospective stroke registry from January 2010 to December 2010.
      RESULTS: Among 174 patients (61.83+/-13.36, 28-90 years), 29 patients (16.7%)
      died during hospitalization. Most common cause of death was initial neurological
      damage (41.4%, 12/29). Seventeen patients who survived the initial damage may
      then develop various potentially fatal complications. Except for death due to the
      initial neurological sequelae, death associated with immobilization (such as
      pneumonia or thromboembolic complication) was the most common in eight cases
      (8/17, 47.1%). However, death due to early rebleeding was not common and occurred
      in only 2 cases (2/17, 11.8%). Age, initial Glasgow Coma Scale, and diabetes
      mellitus were statistically significant factors influencing mortality (p<0.05).
      CONCLUSION: Mortality of n-ICH is still high. Initial neurological damage is the
      most important factor; however, non-neurological medical complications are a
      large part of case fatality. Most cases of death of patients who survived from
      the first bleeding were due to complications of immobilization. These findings
      have implications for clinical practice and planning of clinical trials. In
      addition, future conduct of a randomized study will be necessary in order to
      evaluate the benefits of early mobilization for prevention of immobilization
      related complications.

PMID- 24570811
TI  - Pseudoprogression and pseudoresponse in the management of high-grade glioma :
      optimal decision timing according to the response assessment of the neuro
      oncology working group.
AB  - OBJECTIVE: We evaluated pseudoprogression (PsPD) following radiation therapy
      combined with concurrent temozolomide (TMZ), and we assessed pseudoresponse
      following anti-angiogenic therapy for patients with recurrent disease using the
      Response Assessment of the Neuro-Oncology Working Group. METHODS: Patients who
      were pathologically confirmed as having high-grade glioma received radiotherapy
      with concurrent TMZ followed by adjuvant TMZ. Bevacizumab (Avastin) with CPT-11
      were used as a salvage option for cases of radiologic progression. Magnetic
      resonance imaging (MRI) was routinely performed 1 month after concurrent
      radiochemotherapy (CRT) and every 3 months thereafter. For cases treated with the
      bevacizumab-containing regimen for progressive disease, MRI was performed every 2
      months. RESULTS: Of 55 patients, 21 (38%) showed radiologic progression within 4
      weeks after CRT. Of these patients, 16 (29%) showed progression at second post
      CRT MRI (etPD) and five (9%) showed improvement (PsPD). Seven of thirty-four
      initially non-progressed patients showed progression at the second post-CRT MRI
      (ltPD). No difference in survival was observed between the etPD and ltPD groups
      (p=0.595). Five (50%) of ten patients showed a radiological response after
      salvage bevacizumab therapy. Four of those patients exhibited rapid progression
      immediately after discontinuation of the drug (drug holiday). CONCLUSION: Twelve
      weeks following treatment could be the optimal timing to determine PsPD or true
      progression. MRI with gadolinium enhancement alone is not sufficient to
      characterize tumor response or growth. Clinical correlation with adequate follow
      up duration and histopathologic validation may be helpful in discriminating PsPD
      from true progression.

PMID- 24570812
TI  - Anterior Cervical Discectomy and Fusion Using a Double Cylindrical Cage versus an
      Anterior Cervical Plating System with Iliac Crest Autografts for the Treatment of
      Cervical Degenerative Disc Disease.
AB  - OBJECTIVE: Anterior cervical discectomy and fusion (ACDF) is often complicated by
      subsidence, pseudoarthrosis, kyphosis, and graft donor site morbidities. To
      decrease the occurrence of these complications, various types of cages have been
      developed. We designed this retrospective study to analyze and compare the
      efficacy and outcomes of ACDF using double cylindrical cages (DCC) (BK Medical,
      Seoul, Korea) versus an anterior cervical plating system with autogenous iliac
      crest grafts. METHODS: Forty-eight patients were treated with autograft and
      plating (plate group), and 48 with DCC group from October 2007 to October 2011.
      We analyzed construct length, cervical lordotic curvarture, the thickness of the
      prevertebral soft tissue, segmental instability, and clinical outcomes. RESULTS:
      There were no significant differences between the two groups with regard to the
      decrease in construct length or cervical lodortic curvature at the 3-, 6-, and 12
      month follow-ups. The prevertebral soft tissue was thinner in the DCC group than
      the plate group immediately after surgery and at the 3-, 6-, and 12-month follow
      ups. The difference in interspinous distance on flexion-extension was shorter in
      the plate group than the DCC group at the 3- and 6-month follow-ups. However,
      there was no significant difference in this distance between the two groups at
      the 12-month follow-up. CONCLUSION: A double cylindrical cage is a good
      alternative for fusion in patients with cervical degenerative diseases; the
      surgical method is relatively simple, allows good synostosis, has less associated
      prevertebral soft tissue swelling, and complications associated with autografting
      can be avoided.

PMID- 24570813
TI  - Prognostic factors of neurocognitive and functional outcomes in junior and senior
      elderly patients with traumatic brain injury undergoing disability evaluation or
      appointed disability evaluation.
AB  - OBJECTIVE: This study explored the relationships among demographic (DVs) and
      clinical variables (CVs), neurocognitive (NOs) and functional outcome (FO) that
      could be used as prognostic factors for old aged patients with traumatic brain
      injury (TBI) undergoing or appointed disability evaluation (DE) after treatment.
      METHODS: A total of 162 subjects with TBI above the age of 55 years undergoing DE
      or appointed to do so after treatments were selected. The patients were divided
      into two subgroups according to age : a junior elderly group 55 to 64 years old
      and a senior elderly group over the age of 65. NOs and FO were evaluated using
      the Seoul Neuropsychological Screening Battery and Clinical Dementia Rating
      scale. RESULTS: Gender, age, and education level were shown to significantly
      impact the recovery of NOs after TBI. Other DVs and CVs such as area of
      residency, occupation, type of injury, or loss of consciousness were not found to
      significantly affect the recovery of NOs after TBI. Analysis of the relationships
      among DVs, CVs and NOs demonstrated that gender, age, and education level
      contributed to the variance of NOs. In FO, loss of consciousness (LOC) was
      included to prognostic factor. CONCLUSION: Gender, age and education level
      significantly influence the NOs of elderly patients with TBI. LOC may also serve
      as a meaningful prognostic factor in FO. Unlike younger adult patients with TBI,
      old aged patients with TBI did not show global faking-bad or malingering
      attitudes to DE for compensation, but assume that they could faking their
      performance in a test set available visual feedback.

PMID- 24570814
TI  - Significance of intracranial pressure monitoring after early decompressive
      craniectomy in patients with severe traumatic brain injury.
AB  - OBJECTIVE: Early decompressive craniectomy (DC) has been used as the first stage
      treatment to prevent secondary injuries in cases of severe traumatic brain injury
      (TBI). Postoperative management is the major factor that influences outcome. The
      aim of this study is to investigate the effect of postoperative management, using
      intracranial pressure (ICP) monitoring and including consecutive DC on the other
      side, on the two-week mortality in severe TBI patients treated with early DC.
      METHODS: Seventy-eight patients with severe TBI [Glasgow Coma Scale (GCS) score
      <9] underwent early DC were retrospectively investigated. Among 78 patients with
      early DC, 53 patients were managed by conventional medical treatments and the
      other, 25 patients were treated under the guidance of ICP monitoring, placed
      during early DC. In the ICP monitoring group, consecutive DC on the other side
      were performed on 11 patients due to a high ICP of greater than 30 mm Hg and
      failure to respond to any other medical treatments. RESULTS: The two-week
      mortality rate was significantly different between two groups [50.9% (27
      patients) and 24% (6 patients), respectively, p=0.025]. After adjusting for
      confounding factors, including sex, low GCS score, and pupillary abnormalities,
      ICP monitoring was associated with a 78% lower likelihood of 2-week mortality
      (p=0.021). CONCLUSION: ICP monitoring in conjunction with postoperative
      treatment, after early DC, is associated with a significantly reduced risk of
      death.

PMID- 24570815
TI  - Treatment for giant fusiform aneurysm located in the cavernous segment of the
      internal carotid artery using the pipeline embolization device.
AB  - The pipeline embolization device (PED) is a new endovascular device for treatment
      of complex, fusiform and wide-neck intracranial aneurysms. The main mechanism of
      this stent is to divert the flow in the parent artery with reduction of inflow in
      the aneurysm leading to thrombosis. We treated a 40-year-old woman who had left
      facial pain and orbit discomfort. Angiography showed a giant fusiform aneurysm
      located in the cavernous segment of the left internal carotid artery. A PED was
      successfully deployed across the aneurysm. The procedure and post-procedural
      course were uneventful. After 3 months, angiography showed complete obliteration
      of the aneurysm with good patency of the branching vessels originating from the
      deployed segment. The patient's symptoms improved completely without
      complications. 

PMID- 24570816
TI  - A case of endovascular treatment for followed by side to side bypass for
      vertebral artery dissecting aneurysms involved posterior inferior cerebellar
      artery.
AB  - Treatment of complex aneurysms usually entails not only direct clipping but also
      alternative treatment modality. We recently experienced a case of vertebral
      artery dissecting aneurysm and obtained good treatment outcomes. Our case
      suggests that the endovascular segmental occlusion with posterior inferior
      cerebellar artery (PICA) to PICA side anastomosis might be a good treatment
      option in patients with complex vertebral artery dissecting aneurysms. A 45-year
      old woman has a left vertebral dissecting aneurysm with dizziness. Based on the
      aneurysmal morphology and the involvement of PICA, the patient underwent side to
      side anastomosis of the PICA. This was followed by the endovascular segmental
      coil occlusion. The aneurysmal sac was completely obliterated. At a 2-year follow
      up, the patient achieved a good patency of both PICA. In conclusion our case
      suggests that the endovascular segmental occlusion of the parent artery followed
      by PICA to PICA bypass surgery through a midline suboccipital approach is a
      reasonable multimodal treatment option in patients with complex vertebral artery
      dissecting aneurysms. 

PMID- 24570817
TI  - Two cystic cavernous angiomas after radiotherapy for atypical meningioma in adult
      woman : case report and literature review.
AB  - A correlation between radiation therapy and cavernoma has been suspected since
      1994. Since then, only a few cases of radio-induced cavernomas have been reported
      in the literature (85 patients). Most of them were children, and the most
      frequent original tumour had been medulloblastoma. The authors report a case of
      two cystic cavernous angiomas after radiation therapy for atypical meningioma in
      adult woman. This is the first case of cavernous angioma after radiotherapy for
      low grade meningioma. A 39-year-old, Latin american woman was operated on for a
      frontal atypical meningioma with intradiploic component and adjuvant radiotherapy
      was delivered (6000 cGy local brain irradiation, fractionated over 6 weeks).
      Follow-up MR imaging showed no recurrences of the tumour and no other lesions.
      Ten years later, at the age of 49, she consulted for progressive drug-resistant
      headache. MR imaging revealed two new well defined areas of different signal
      intensity at the surface of each frontal pole. Both lesions were surgically
      removed; the histopathological diagnosis was cavernous angioma. This is the first
      case of cavernous angioma after radiation therapy for atypical meningioma : it
      confirms the development of these lesions after standard radiation therapy also
      in patients previously affected by non-malignant tumours. 

PMID- 24570818
TI  - Spinal cord ependymoma associated with neurofibromatosis 1 : case report and
      review of the literature.
AB  - Patients with neurofibromatosis 1 (NF1) are predisposed to develop central
      nervous system tumors, due to the loss of neurofibromin, an inactivator of proto
      oncogene Ras. However, to our knowledge, only three cases of ependymomas with NF1
      have been reported in the literature. The authors present a case of NF1 patient
      with a spinal cord ependymoma. She was referred for about half a year history of
      increasing numbness that progressed from her fingers to her entire body above the
      bellybutton. Magnetic resonance imaging revealed a relative-demarcated,
      heterogeneously enhanced mass lesion accompanied by perifocal edema in C5-7
      level, a left-sided T11 spinous process heterogeneously enhanced mass in soft
      tissue, intervertebral disk hernia in L2-5 level, and widespread punctum
      enhancing lesion in her scalp and in T11-L5 level. The patient underwent C5-7
      laminectomies and total excision of the tumor under operative microscope, and
      intraoperative ultrasonography and physiological monitoring were used during the
      surgery. Histopathologically, her tumor was found to be a ependymoma without
      malignant features (grade II in the World Health Organization classification).
      Therefore, no adjuvant therapy was applied. Following the operation, the patient
      showed an uneventful clinical recovery with no evidence of tumor recurrence after
      one year of follow-up. 

PMID- 24570819
TI  - Collapsed L4 vertebral body caused by brucellosis.
AB  - Brucellosis is caused by gram-negative, aerobic, non-motile, facultative,
      intracellular coccobacilli belonging to the genus Brucella. A 50-year-old man
      working as an employee was admitted to neurosurgery clinic with severe low back,
      radicular right leg pain and hypoesthesia in right L4-5 dermatomes for 2 months.
      Brucella tube agglutination (Wright) test was positive in serum sample of the
      patient with a titer of 1/640. Brucella melitensis was isolated from blood
      culture. X-ray and MRI of the lomber spine showed massive collapse of L4
      vertebral body. Neural tissue was decompressed and then posterior L3-5 short
      segment transpedicular screw fixation and stabilization was performed. Brucella
      melitensis was isolated from microbiologic culture of pathologic specimen.
      Antibiotic therapy was given as doxycycline 200 mg/day and rifampicin 600 mg/day
      for 6 months. Brucellosis is a systemic zoonotic infection and still an important
      public health problem in many geographical parts of the world. Vertebral body
      collapse caused by brucellosis occurs very rarely but represents a neurosurgical
      emergency because of its potential for causing rapidly progressive spinal cord
      compression and permanent paralysis. Neurosurgeons, emergency department
      personnel as well as infectious disease specialists should always keep a high
      index of suspicion and include brucellosis in the differential diagnosis of
      vertebral body collapse. 

PMID- 24570820
TI  - Patients on Anticoagulants after a Head Trauma : Is a Negative Initial CT Scan
      Enough? Report of a Case of Delayed Subdural Haematoma and Review of the
      Literature.
AB  - Mild traumatic brain injury is common in elderly patients, many of whom are on
      anticoagulant. The common practice is to discharge these patients from the
      emergency room if the computed tomography (CT) of the brain is normal. However, a
      very small proportion of these patients may develop a life threatening
      intracranial haematoma in the following days. We present here a case of a 66-year
      old male on anticoagulant therapy that developed a subdural haematoma 48 hours
      after a mild head injury, with a normal initial CT scan of the brain. The patient
      underwent a craniotomy with evacuation of a large subdural clot. Postoperatively
      he had progressively improved and six months later has a Glasgow Outcome Score of
      three. This case is characterized by the delayed onset of a subdural haematoma in
      a patient on anticoagulation and we discuss here the possible pathogenesis
      related to this phenomenon. We also briefly review the pertinent literature and
      the current guidelines for the management of this type of head injuries. 

PMID- 24570821
TI  - Should adjuvant radiotherapy be recommended for pediatric craniopharyngiomas?
AB  - Intracranial tumors secondary to radiotherapy are rare. In this group gliomas are
      the rarest. Only 6 cases of glioblastoma multiforme (GBM) have been reported in
      patients undergoing radiotherapy (RT) for craniopharyngiomas of which only 4 have
      been in children less than 18 years of age. In recent years RT has become a
      mainstay of adjuvant therapy for recurrent or partially excised
      craniopharyngiomas. We report a child of 12 years who had previously undergone RT
      for a suprasellar craniopharyngioma and presented 10 years later with a GBM. This
      is the 5th pediatric case in literature demonstrating a GBM after RT for a
      craniopharyngioma. The implications of subjecting the pediatric population to RT
      for a benign lesion versus the outcome of gross total removal and management of
      RT induced tumors is discussed and the need to avail of safer alternatives such
      as stereotactic radiosurgery is stressed. 

PMID- 24570822
TI  - Malignant rhabdoid tumor of the kidney and spine in an infant.
AB  - Rhabdoid tumor of the kidney (RTK) is a rare malignancy in infancy. Central
      nervous system involvement in RTK is already known. However, solitary spinal
      metastasis in RTK has been hardly reported. The authors report a case of
      metastatic RTK to spine causing paraplegia in an 8-month-old girl. Since the
      patient was young, the diagnosis of spine metastasis was delayed until paraplegia
      was seen after radical nephrectomy. Thorough neurological examination should be
      performed for early diagnosis of spinal metastasis in young patients with RTK. If
      there are any abnormal signs in neurologic examination, magnetic resonance images
      of brain and spine are recommended. 

PMID- 24570823
TI  - Solitary cavernous sinus neurosarcoidosis mimicking neurosyphilis.
AB  - A differential diagnosis between neurosarcoidosis and neurosyphilis is
      particularly problematic in patients with a positive serologic result for
      syphilis. We report here a patient with a solitary cavernous sinus sarcoidosis
      who had a history of syphilis and showed rapidly progressing cavernous sinus
      syndrome. A transsphenoidal biopsy was performed and a histopathologic
      examination revealed a non-caseating granuloma with an asteroid body. His facial
      pain disappeared after steroid therapy. He received oral prednisolone for one
      year. A follow-up magnetic resonance imaging of the brain revealed resolution of
      the mass over the cavernous sinus. Particularly in patients with a history of
      syphilis, neurosyphilis should be included in a differential diagnosis of
      neurosarcoidosis. 

PMID- 24570824
TI  - Significance of Arachnoid Dissection to Obtain Optimal Exposure of Lower Cranial
      Nerves and the Facial Nerve Root Exit Zone during Microvascular Decompression
      Surgery.

PMID- 24570825
TI  - Combination antioxidant effect of erythropoietin and melatonin on renal ischemia
      reperfusion injury in rats.
AB  - OBJECTIVE(S): Renal ischemia reperfusion (IR) contributes to the development of
      acute renal failure (ARF). Oxygen free radicals are considered to be principal
      components involved in the pathophysiological tissue alterations observed during
      renal IR. The purpose of this study was to investigate the effect of co
      administration of melatonin (MEL) and erythropoietin (EPO), potent antioxidant
      and anti-inflammatory agents, on IR-induced renal injury in rats. MATERIALS AND
      METHODS: Wistar albino rats were unilaterally nephrectomized and subjected to 45
      min of renal pedicle occlusion followed by 24 hr reperfusion. MEL (10 mg/kg, IP)
      and EPO (5000 U/kg, IP) were administered prior to ischemia. After 24 hr
      reperfusion, following decapitation, renal samples were taken for the
      determination of malondialdehyde (MDA), superoxide dismutase (SOD), catalase
      (CAT), glutathione peroxidase (GPx) levels and histological evaluation. The level
      of urea was measured in serum samples. RESULTS: Ischemia reperfusion
      significantly increased urea, and MDA levels, and decreased CAT and SOD
      activities. Histopathological findings of the IR group confirmed that there was
      renal impairment in the tubular epithelium. Treatment with EPO and MEL markedly
      decreased urea level and increased SOD and GPx activities. CONCLUSION: Treatment
      with EPO and MEL had a beneficial effect on renal IR injury. These results may
      show that the co-administration of MEL and EPO cannot exert more beneficial
      effects than either agent alone.

PMID- 24570826
TI  - Dose Ramadan Fasting Affects Inflammatory Responses: Evidences for Modulatory
      Roles of This Unique Nutritional Status via Chemokine Network.
AB  - OBJECTIVE(S): The impact of fasting in Ramadan as a unique type of nutritional
      regimen on biochemical and hematological parameters is still an issue of debate.
      Almost very little is known regarding the regulatory role(s) of this nutritional
      status on immune responses or inflammation. MATERIALS AND METHODS: The levels of
      biochemical parameters were determined using commercial diagnostic kits.
      Hematological parameters were also examined. We also employed ELISA for detection
      of CXCL1, CXCL10 and CXCL12 chemokines. The Student-T test was used to compare
      the values of different parameters obtained in the first and last day of Ramadan
      fasting by employing SPSS (version 18) software. RESULTS: As our findings
      demonstrated, there was a markedly difference between before and after Ramadan
      BMI of the individuals who fast. Our results also revealed that there was a
      remarkable difference between the levels of total cholesterol, FBS, Triglycerides
      and LDL before and after Ramadan fasting. RESULTS revealed that among studied
      hematological parameters only the numbers of platelets were markedly different
      before and after Ramadan fasting program in individuals who practice fasting. Our
      results also showed decreased levels of pro-inflammatory CXC chemokines but
      unaltered levels of homoeostatic ones. CONCLUSION: The results of this study may
      reveal that Ramadan fasting is quite safe for normal healthy adults and so very
      useful in reduction of cholesterol and triglycerides in relation with
      dyslipidemia. It is also possible to conclude that fasting is important in
      controlling of inflammation via chemokines.

PMID- 24570828
TI  - Evaluation of serum interleukins-6, 8 and 10 levels as diagnostic markers of
      neonatal infection and possibility of mortality.
AB  - OBJECTIVE(S): Bacterial infection contributes substantially to neonatal morbidity
      and mortality. Early diagnosis of neonatal sepsis is difficult because clinical
      signs are non-specific. We have evaluated serum IL-6, 8 and 10 as potential early
      diagnostic markers of neonatal infection and their relationship to mortality rate
      and poor prognosis. Materials and Methods : A total of 84 infants, aged >= 72 hr
      were enrolled in this prospective case-control trial. The case group (n=41)
      included babies with clinical and laboratory findings compatible with sepsis
      and/or positive blood or cerebrospinal fluid cultures. The control group (n=43)
      included healthy infants. IL-6, 8 and 10 were measured for all infants. Receiver
      operating characteristic (ROC) curves were used for the determination of
      thresholds. Results : Statistically significant differences were observed between
      control and case groups for serum median level of IL-6, 8 and 10 (P<0.001). IL-6
      cut-off values of 10.85 Pg/ml for discriminating between cases and controls and
      78.2 Pg/ml for predicting mortality are suggested. IL-8 at a cut-off value of
      60.05 Pg/ml was valuable for differentiation of definite versus indefinite
      infection. Conclusion : Evaluating the IL-6, 8 and 10 simultaneously, could
      improve the sensitivity and specificity of early diagnosis of the neonatal
      sepsis. Regarding our results, interleukin 6 had the greatest value for
      predicting infection and possible mortality, whereas IL-8 was valuable for
      diagnosing definitive infection.

PMID- 24570827
TI  - Aripiprazole-cyclodextrin binary systems for dissolution enhancement: effect of
      preparation technique, cyclodextrin type and molar ratio.
AB  - OBJECTIVE(S): The aim of this work was to investigate the effect of the natural
      and the chemically modified form of cyclodextrins namely; beta-cyclodextrin (beta
      CD) and hydroxypropyl-beta-cyclodextrin (HP-beta-CD) respectively on the
      solubility and dissolution rate of aripiprazole; an antipsychotic medication
      showing poor aqueous solubility. MATERIALS AND METHODS: Phase solubility of
      aripiprazole with the studied CDs and the complexation efficiency values (CE)
      which reflect the solubilizing power of the CDs towards the drug was performed.
      Solid binary systems of aripiprazole with CDs were prepared by kneading,
      microwave irradiation and freeze-drying techniques at 1:1 and 1:2 (drug to CD)
      molar ratios. Drug-CD physical mixtures were also prepared in the same molar
      ratios for comparison. The dissolution of aripiprazole-binary systems was carried
      out to select the most appropriate CD type, molar ratio and preparation
      technique. RESULTS: Phase solubility study indicated formation of higher order
      complexes and the complexation efficiency values was higher for HP-beta-CD
      compared to beta-CD. Drug dissolution study revealed that aripiprazole
      dissolution was increased upon increasing the CD molar ratio and, the freeze
      drying technique was superior to the other studied methods especially when
      combined with the HP-beta-CD. The cyclodextrin type, preparation technique and
      molar ratio exhibited statistically significant effect on the drug dissolution at
      P<= 0.05. CONCLUSION: The freeze-dried system prepared at molar ratio 1:2 (drug:
      CD) can be considered as efficient tool for enhancing aripiprazole dissolution
      with the possibility of improving its bioavailability.

PMID- 24570829
TI  - Synthesis, Anti-Inflammatory and Anti- Nociceptive Activities and Cytotoxic
      Effect of Novel Thiazolidin-4-ones Derivatives as Selective Cyclooxygenase (COX
      2) Inhibitors.
AB  - OBJECTIVE(S): Nowadays, COX - 2 inhibitors such as valdecoxib are removed from
      the market because of their cardiovascular toxicity and their potential to
      increase the risk of strokes. In response to this, medicinal chemists have
      attempted to synthesize new classes of COX-2 Inhibitors. MATERIALS AND METHODS:
      In this study, three novel analogues of thiazolidin-4-ones derivatives 2a-c were
      synthesized. The ability of these compounds to inhibit ovine COX-1 and COX-2 (0.2
      0.8 uM) was determined using a colorimetric method. The cytotoxic effect of the
      synthesized compounds (25-100 M) was also investigated by measuring their
      cytotoxicity against Caco-2 and MCF-7 cell lines using MTT assay. Cell apoptosis
      was determined by flow cytometry. Writhing test (7.5-75 mg/kg) was used to
      examine the antinociceptive effects in mice. The effect of the analogues against
      acute inflammation (7.5-75 mg/kg) was also studied using xylene-induced ear edema
      test in mice. RESULTS: The synthesized compounds showed a weak capacity to
      inhibit the proliferation of Caco-2 and MCF-7 cell lines. The COX-2 inhibition
      potency and selectivity index for test compounds 2a-b were as follows; celecoxib
      > 2b > 2a. On the other hand, all three analogues exhibited strong
      antinociceptive activity against acetic acid-induced writhing. The anti
      inflammatory and antinociceptive effects of the analogues were markedly more than
      positive control, celecoxib. CONCLUSION: This study demonstrates that the
      antinociceptive and anti-inflammatory activity profiles exhibited by the novel
      synthesized compounds are independent from their COX-2 inhibitory potencies. The
      found antinociceptive and anti-inflammatory effects can be caused by interaction
      with other target; independent from COX-2. Accordingly, the compounds 2a-c could
      serve as lead compounds to develop novel anti-inflammation and antinociceptive
      drugs.

PMID- 24570830
TI  - Partial Optimization of Endo-1, 4-Beta-Xylanase Production by Aureobasidium
      pullulans Using Agro-Industrial Residues.
AB  - Objective(s) : Although bacteria and molds are the pioneering microorganisms for
      production of many enzymes, yet yeasts provide safe and reliable sources of
      enzymes with applications in food and feed. MATERIALS AND METHODS: Single
      xylanase producer yeast was isolated from plant residues based on formation of
      transparent halo zones on xylan agar plates. The isolate showed much greater endo
      1, 4-beta-xylanase activity of 2.73 IU/ml after optimization of the initial
      extrinsic conditions. It was shown that the strain was also able to produce beta
      xylosidase (0.179 IU/ml) and alpha-arabinofuranosidase (0.063 IU/ml).
      Identification of the isolate was carried out and the endo-1, 4-beta
      xylanaseproduction by feeding the yeast cells on agro-industrial residues was
      optimized using one factor at a time approach. RESULTS: The enzyme producer
      strain was identified as Aureobasidiumpullulans. Based on the optimization
      approach, an incubation time of 48 hr at 27 degrees C, inoculum size of 2% (v/v),
      initial pH value of 4 and agitation rate of 90 rpm were found to be the optimal
      conditions for achieving maximum yield of the enzyme. Xylan, containing
      agricultural residues, was evaluated as low-cost alternative carbon source for
      production of xylanolytic enzymes. The production of xylanase enzyme in media
      containing wheat bran as the sole carbon source was very similar to that of the
      medium containing pure beechwoodxylan. CONCLUSION: This finding indicates the
      feasibility of growing of A. pullulans strain SN090 on wheat bran as an alternate
      economical substrate in order for reducing the costs of enzyme production and
      using this fortified agro-industrial byproduct in formulation of animal feed.

PMID- 24570831
TI  - Expression of acrA and acrB Genes in Esherichia coli Mutants with or without marR
      or acrR Mutations.
AB  - OBJECTIVE(S): The major antibiotic efflux pump of Esherichia coli is AcrAB-TolC.
      The first part of the pump, AcrAB, is encoded by acrAB operon. The expression of
      this operon can be kept elevated by overexpression of an activator, MarA
      following inactivation of MarR and AcrR repressors due to mutation in encoding
      genes, marR and acrR, respectively. The aims of this research were to use E. coli
      mutants with or without mutation in marR to search for the presence of possible
      mutation in acrR and to quantify the expression of acrAB. MATERIALS AND METHODS:
      The DNA binding region of acrR gene in these mutants were amplified by PCR and
      sequenced. The relative expression of acrA and acrB were determined by real time
      PCR. RESULTS: RESULTS showed that W26 and C14 had the same mutation in acrR, but
      none of the mutants overexpressed acrA and acrB in comparison with wild type
      strain. CONCLUSIONS: The effect of marR or acrR mutation on acrAB overexpression
      is dependent on levels of resistance to tetracycline and ciprofloxacin.

PMID- 24570832
TI  - An efficient covalent coating on glass slides for preparation of optical
      oligonucleotide microarrays.
AB  - OBJECTIVE(S): Microarrays are potential analyzing tools for genomics and
      proteomics researches, which is in needed of suitable substrate for coating and
      also hybridization of biomolecules. MATERIALS AND METHODS: In this research, a
      thin film of oxidized agarose was prepared on the glass slides which previously
      coated with poly-L-lysine (PLL). Some of the aldehyde groups of the activated
      agarose linked covalently to PLL amine groups; also bound to the amino groups of
      biomolecules. These linkages were fixed by UV irradiation. The prepared
      substrates were compared to only agarose-coated and PLL-coated slides. RESULTS:
      RESULTS on atomic force microscope (AFM) demonstrated that agarose provided three
      dimensional surface which had higher loading and bindig capacity for biomolecules
      than PLL-coated surface which had two-dimensional surface. In addition, the
      signal-to-noise ratio in hybridization reactions performed on the agarose-PLL
      coated substrates increased two fold and four fold compared to agarose and PLL
      coated substrates, respectively. CONCLUSION: The agarose-PLL microarrays had the
      highest signal (2546) and lowest background signal (205) in hybridization,
      suggesting that the prepared slides are suitable in analyzing wide concentration
      range of analytes.

PMID- 24570833
TI  - A Consistent PCR-RFLP Assay Based on ITS-2 Ribosomal DNA for Differentiation of
      Fasciola Species.
AB  - OBJECTIVE(S): Fascioliasis is a zoonotic parasitic disease caused by liver fluke
      species of Fasciola hepatica and Fasciola gigantica. Differentiation of these two
      species, based on their morphological characteristics, is difficult. The current
      study aimed to use PCR-RFLP assay to distinguish between F. hepatica and F.
      gigantica, based on profiles of RFLP, produced by effect of endonucleases on ITS2
      of the ribosomal DNA genes from these two species. MATERIALS AND METHODS: Adult
      Fasciola spp. were isolated from bile duct of naturally infected animals. The
      species of Fasciola were confirmed by sequencing the 505 bp region of the ITS2
      gene in the isolates. By running the sequences of the samples in NEBcutter,
      suitable restriction enzymes (MspI and KpnI) were selected. Eight F. gigantica
      and eighteen F. hepatica samples were evaluated. RESULTS: While RFLP pattern with
      MspI produced a profile by which it was difficult to differentiate these two
      species, KpnI along with MspI, produced a consistent pattern of a 231, 212 and 93
      bp fragments in F. hepatica. This pattern was not seen in F. gigantica.
      CONCLUSION: Findings of this study demonstrated that RFLP with KpnI and MspI
      produce a suitable pattern which simply differentiates F. hepatica from F.
      gigantica.

PMID- 24570834
TI  - 8-OH-DPAT (5-HT1A agonist) Attenuates 6-Hydroxy- dopamine-induced catalepsy and
      Modulates Inflammatory Cytokines in Rats.
AB  - OBJECTIVE(S): Neuroinflammation in Parkinson disease (PD) is associated with
      glial cells activation and production of different inflammatory cytokines. In
      this study, we investigated the effect of chronic administration of 8-OH-DPAT on
      6-OHDA-induced catalepsy and levels of inflammatory cytokines in cerebrospinal
      fluid (CSF). MATERIALS AND METHODS: Catalepsy was induced by unilateral infusion
      of 6-OHDA (8 MUg/2 MUl/rat) into the central region of the sabstantia nigra pars
      compacta (SNc) being assessed by the bar-test, 5, 60, 120 and 180 min after
      intraperitoneal (IP) administration of 8-OH-DPAT (5-HT1A receptor agonist; 0.25,
      0.5 and 1mg/kg, IP for 10 days). CSF samples were collected on the tenth day of 8
      OH-DPAT administration and analyzed by ELISA method to measure levels of TNF
      alpha, IL-1beta and IL-6. RESULTS: Chronic injection of 8-OH-DPAT decreased
      catalepsy in a dose dependent manner when compared with the control group. The
      most anti-cataleptic effect was observed at the dose of 1 mg/kg of 8-OH-DPAT.
      Levels of TNF-alpha in CSF increased three weeks after 6-OHDA injection while
      there was a significant decrease in TNF-alpha level of parkinsonian animals
      treated with 8-OH-DPAT (1 mg/kg, IP for 10 days). IL-1beta and IL-6 decreased and
      increased in parkinsonian rats and in 8-OH-DPAT-treated parkinsonian rats,
      respectively. CONCLUSION: Our study indicated that chronic administration of 8-OH
      DPAT improves catalepsy in 6-OHDA-induced animal model of PD and restores central
      concentration of inflammatory cytokines to the basal levels. 5-HT1A receptor
      agonists can be suggested as potential adjuvant therapy in PD by modulation of
      cerebral inflammatory cytokines.

PMID- 24570835
TI  - PKCa Agonists Enhance the Protective Effect of Hyaluronic Acid on Nitric Oxide
      Induced Apoptosis of Articular Chondrocytes in Vitro.
AB  - OBJECTIVE(S): Protein kinase C (PKCalpha) is involved in modulating articular
      chondrocytes apoptosis induced by nitric oxide (NO). Hyaluronic acid (HA)
      inhibits nitric oxide-induced apoptosis of articular chondrocytes by protecting
      PKCalpha, but the mechanism remains unclear. The present study was performed to
      investigate the effects and mechanisms of PKCalpha regulate protective effect of
      hyaluronic acid. Materials and Methods The ratio of apoptotic cell and cell
      viability was surveyed by PCNA and MTT assay. The expression of caspase-3 was
      determined by real-time PCR and western blot. RESULTS: It was showed that HA was
      able to reduce the nuclei fragment and PCNA expression, and NO-induced articular
      apoptosis blocked by HA, pretreated chondrocytes with PMA, HA significantly
      inhibits the activation of caspase-3 induced by NO, but pretrement with CHR, HA
      significantly incresed the expression of caspase-3. CONCLUSION: The results may
      be showed that PKCa regulate the expresion of caspase-3, which contribute to the
      apoptosis of chondrocytes induced by NO. PKC alpha agonists enhance the
      protective effect of hyaluronic acid on nitric oxide-induced articular
      chondrocytes apoptosis.

PMID- 24570836
TI  - Effect of phenobarbital on chloramphonicol-induced toxicity in rat liver and
      small intestine.
AB  - OBJECTIVE(S): The aim of the present study is to determine the effect of
      Chloramphenicol (CAP) on rat liver and small intestine. Effect of phenobarbital
      (PB) on CAP toxicity was also investigated. MATERIALS AND METHODS: Rats were
      received CAP at doses of 0, 200, 400 and 600 mg/kg. Another group was pretreated
      with 80 mg/kg PB 30 min prior to administration of various doses of CAP. The
      experiment was repeated for seven consecutive days. Blood was collected for
      determination of serum aspartate aminotransferase (AST) alanine aminotransferase
      (ALT). The liver and small intestine tissues were processed for light microscopy.
      RESULTS: CAP induced a dose dependent elevation of AST and ALT and produced
      injury in the liver and small intestine when compared to control animals. PB
      markedly decreased AST and ALT levels and protected liver and small intestine
      against CAP-induced toxicity. Conclusion : This study suggested rat liver and
      small intestine have potential to bioactivate CAP.

PMID- 24570838
TI  - Risk awareness in secondary stroke prevention: a review of the literature.
AB  - Despite improvements in the diagnosis and treatment of cardiovascular disease
      through medical advances, it remains the largest single cause of disability and
      the second leading cause of death on a global scale. Despite this, patient
      awareness of cardiovascular risk is low and adherence to secondary prevention
      measures is inadequate. This combined with an ageing population could have
      serious consequences for both personal and health care costs. Risk management has
      been used to design strategies to prevent both primary and secondary stroke.
      These strategies have largely relied upon health professionals providing
      information, support and monitoring of patients conditions and control of
      individual risk factors. However, these strategies have not always been
      successful in the long-term management and prevention of secondary cardiovascular
      disease. This review explores the literature surrounding risk awareness as a tool
      to improve patient adherence to medications and lifestyle behaviours to reduce
      risk of secondary stroke. 

PMID- 24570837
TI  - Imaging biomarkers for antiangiogenic   therapy in malignant gliomas.
AB  - The discovery that malignant gliomas produce an excessive amount of VEGF, a key
      mediator of angiogenesis, has heightened interest in developing drugs that block
      angiogenic pathways. These antiangiogenic drugs tend to decrease vascular
      permeability, thereby diminishing tumor contrast enhancement independent of anti
      tumor effects. This has made the determination of tumor response difficult, since
      contrast enhancement on post-contrast T1-weighted images is standard for
      assessing therapy effectiveness. In light of these unique challenges in assessing
      antiangiogenic therapy, new biomarkers have been proposed, based on advanced
      magnetic resonance techniques and PET. This article outlines the challenges
      associated with the evaluation of antiangiogenic therapy in malignant gliomas and
      describes how new imaging biomarkers can be used to better predict response.

PMID- 24570839
TI  - Aldosterone synthase inhibitors in hypertension: current status and future
      possibilities.
AB  - The renin-angiotensin aldosterone system is a critical mechanism for controlling
      blood pressure, and exerts most of its physiological effects through the action
      of angiotensin II. In addition to increasing blood pressure by increasing
      vascular resistance, angiotensin II also stimulates aldosterone secretion from
      the adrenal gland. Aldosterone acts to cause an increase in sodium and water
      reabsorption, thus elevating blood pressure. Although treatment with angiotensin
      converting enzyme inhibitors initially lowers circulating aldosterone, with
      chronic treatment aldosterone levels increase back to baseline, a phenomenon
      termed aldosterone escape; aldosterone blockade may therefore give added value in
      the treatment of hypertension. The first mineralocorticoid receptor antagonist
      developed was spironolactone, but its use has been severely hampered by adverse
      (notably oestrogenic) effects. The more recently developed mineralocorticoid
      receptor antagonist eplerenone exhibits a better adverse effect profile, although
      it is not devoid of effects similar to spironolactone. In addition, aldosterone
      activates non-genomic receptors that are not inhibited by either eplerenone or
      spironolactone. It is believed that deleterious organ remodelling is mediated by
      aldosterone via such non-genomic pathways. A new class of drugs, the aldosterone
      synthase inhibitors, is currently under development. These may offer a novel
      therapeutic approach for both lowering blood pressure and preventing the non
      genomic effects of aldosterone. Here, we will review the cardiovascular effects
      of aldosterone and review the drugs available that target this hormone, with a
      particular focus on the aldosterone synthase inhibitors. 

PMID- 24570840
TI  - BRG1 Is Required to Maintain Pluripotency of Murine Embryonic Stem Cells.
AB  - BAF chromatin remodeling complexes containing the BRG1 protein have been shown to
      be not only essential for early embryonic development, but also paramount in
      enhancing the efficiency of reprogramming somatic cells to pluripotency mediated
      by four transcription factors. To investigate the role of BRG1 in regulating
      pluripotency, we found that Oct4 and Nanog levels were increased immediately
      after BRG1 knockdown. While Nanog levels remained elevated over the investigated
      time period, Oct4 levels decreased at later time points. Additionally, OCT4
      target genes were also found to be upregulated upon Brg1 knockdown. SiRNA
      mediated BRG1 knockdown in embryonic stem (ES) cells led to Oct4 and Nanog
      upregulation, whereas F9 cells showed primarily Oct4 upregulation. BRG1 knockdown
      upregulated the expression of differentiation markers in mouse ES cells as well
      as differentiated morphology under reduced leukemia inhibitory factor conditions.
      Our results show that BRG1 plays an important role in maintaining pluripotency by
      fine-tuning the expression level of Oct4 and other pluripotency-associated genes.

PMID- 24570841
TI  - Culture expansion in low-glucose conditions preserves chondrocyte differentiation
      and enhances their subsequent capacity to form cartilage tissue in three
      dimensional culture.
AB  - Culture conditions that preserve a stable chondrocyte phenotype are desirable in
      cell-based cartilage repair to maximize efficacy and clinical outcome. This study
      investigates whether low-glucose conditions will preserve the chondrocyte
      phenotype during culture expansion. Articular chondrocytes were culture-expanded
      in media supplemented with either low (1 mM) or high (10 mM) glucose. The
      metabolic phenotype, reactive oxygen species generation, and mRNA expression of
      markers of differentiation or catabolism were assessed by reverse-transcription
      quantitative polymerase chain reaction after four population doublings (PDs) and
      subsequent tissue formation capacity determined using pellet cultures. Continuous
      monolayer culture was used to determine the population doubling limit. After
      expansion in monolayer for four PDs, chondrocytes expanded in low-glucose
      conditions exhibited higher expression of the differentiation markers SOX9 and
      COL2A1 and reduced expression of the catabolic metalloproteinase matrix
      metallopeptidase 13. When chondrocytes expanded in low glucose were cultured in
      micropellets, they consistently generated more cartilaginous extracellular matrix
      than those expanded in high glucose, as evaluated by wet weight, sulfated
      glycosaminoglycan content, and hydroxyproline assay for collagen content. The
      same pattern was observed whether high or low glucose was used during the pellet
      culture. During expansion, chondrocytes in high-glucose generated 50% more
      reactive oxygen species than low-glucose conditions, despite a lower dependence
      on oxidative phosphorylation for energy. Furthermore low-glucose cells exhibited
      >30% increased population doubling limit. These data suggests that low-glucose
      expansion conditions better preserve the expression of differentiation markers by
      chondrocytes and enhance their subsequent capacity to form cartilage in vitro.
      Therefore, low glucose levels should be considered for the expansion of
      chondrocytes intended for tissue engineering applications. 

PMID- 24570842
TI  - Programmable mechanobioreactor for exploration of the effects of periodic
      vibratory stimulus on mesenchymal stem cell differentiation.
AB  - A programmable bioreactor using a voice-coil actuator was developed to enable
      research on the effects of periodic vibratory stimulus on human and porcine
      mesenchymal stem cells (MSCs). We hypothesized that low frequency vibrations
      would result in a cartilage phenotype and higher frequency vibrations would
      result in a bone phenotype. The mechanical stimulation protocol is adjusted from
      a computer external to the incubator via a USB cable. Once programmed, the
      embedded microprocessor and sensor system on the bioreactor execute the protocol
      independent of the computer. In each test, a sinusoidal stimulus was applied to a
      culture plate in 1-min intervals with a 15-min rest following each, for a total
      of 15 h per day for 10 days. Frequencies of 1 and 100 Hz were applied to cultures
      of both human and porcine umbilical cord-derived MSCs. Chondrogenesis was
      determined by Alcian blue staining for glycosaminoglycans and an increased
      differentiation index (ratio of mRNA for collagen II and collagen I). Osteogenic
      differentiation was indicated with Alizarin red for calcium staining and
      increased bone morphogenetic protein 2 mRNA. One-hertz stimulation resulted in a
      cartilage phenotype for both human and porcine MSCs, while 100-Hz stimulation
      resulted in a bone phenotype. 

PMID- 24570843
TI  - The Effect of Recombinant Human Interleukin-6 on Osteogenic Differentiation and
      YKL-40 Expression in Human, Bone Marrow-Derived Mesenchymal Stem Cells.
AB  - Human mesenchymal stem cells are an attractive cell source for tissue engineering
      and regenerative medicine applications, especially because of their
      differentiation potential toward the mesenchymal lineage. Furthermore, this cell
      type participates in the regeneration of tissue damage and plays an important
      role in immunity. Similarly, chitinase-like proteins have been proposed to aid in
      tissue remodeling, inflammation, and differentiation processes. The chitinase
      like protein YKL-40 in particular is indicated in preventing damage to the
      extracellular matrix in response to proinflammatory cytokines, even though its
      biological function remains speculative. Finally, interleukin (IL)-6, a
      pleiotropic acute phase protein, participates in the regulation of bone turnover
      and immunoregulation. The physiological role of IL-6 in bone homeostasis is
      complex, exerting different effects on osteoblasts and osteoclasts depending on
      their differentiation stage. The aim of this study was to determine the effect of
      recombinant human IL-6 (5 ng/mL) on YKL-40 expression and osteogenic
      differentiation of human mesenchymal stem cells. Recombinant human IL-6 induced a
      donor-dependent change in mineralization and significantly promoted YKL-40
      protein secretion. However, YKL-40 gene expression remained unaffected, and no
      statistically significant differences in the expression of osteogenic marker
      genes could be observed. 

PMID- 24570844
TI  - Physico-chemical factors influencing autologous conditioned serum purification.
AB  - Autologous conditioned serum (ACS) is a recent biotherapy based on certain
      cytokines anti-inflammatory properties mainly used for the reduction of
      osteoarthritis (OA) symptoms. Here we investigated different physico-chemical
      factors influencing ACS purification and cytokine production. Human venous blood
      was incubated in the presence of different diameter beads (respectively 2.5, 3,
      3.5, and 4 mm) or glass beads with different types of coating (polished or coated
      with CrSO4). Sera were recovered, and the concentrations of pro-inflammatory and
      anti-inflammatory relevant cytokines were measured using Luminex((r)) technology.
      Fresh whole blood incubated for 24 h highly increased production of interleukin
      (IL)-6 and IL-8 cytokines. At the same time, the concentrations of IL-1beta, IL-1
      receptor agonist (IL-1Ra), IL-10, and tumor necrosis factor (TNF)-alpha were
      slightly induced. The highest cytokine concentrations were obtained with the
      exposure of whole blood to 3-mm glass beads and 3.5-mm polished beads. The
      minimum IL-1beta/IL-1Ra ratio obtained was 3.2+/-1.3 after 24-h incubation
      without any beads. ACS has been shown to alleviate clinical symptoms of OA in
      clinical studies. This descriptive study demonstrated that different pro- and
      anti-inflammatory cytokines are present in ACS since no selective anti
      inflammatory cytokines were produced based on the different protocols.
      Furthermore, we showed that CrSO4-treated glass beads are not necessary and that
      the absence of beads combined with a 24-h incubation could also lead to an
      enriched serum. 

PMID- 24570845
TI  - Traveling wave solutions of the Boussinesq equation via the new approach of
      generalized (G'/G)-expansion method.
AB  - ABSTRACT: Exact solutions of nonlinear evolution equations (NLEEs) play a vital
      role to reveal the internal mechanism of complex physical phenomena. In this
      work, the exact traveling wave solutions of the Boussinesq equation is studied by
      using the new generalized (G'/G)-expansion method. Abundant traveling wave
      solutions with arbitrary parameters are successfully obtained by this method and
      the wave solutions are expressed in terms of the hyperbolic, trigonometric, and
      rational functions. It is shown that the new approach of generalized (G'/G)
      expansion method is a powerful and concise mathematical tool for solving
      nonlinear partial differential equations in mathematical physics and engineering.
      PACS: 05.45.Yv, 02.30.Jr, 02.30.Ik.

PMID- 24570846
TI  - Comparative study of the adsorption of acetaminophen on activated carbons in
      simulated gastric fluid.
AB  - Samples of commercial activated carbons (AC) obtained from different sources:
      Norit E Supra USP, Norit B Test EUR, and ML (Baracoa, Cuba) were investigated.
      The adsorption of acetaminophen, Co = 2500 mg/L, occured in simulated gastric
      fluid (SGF) at pH 1.2 in contact with activated carbon for 4 h at 310 K in water
      bath with stirring. Residual acetaminophen was monitored by UV visible. The
      results were converted to scale adsorption isotherms using alternative models:
      Langmuir TI and TII, Freundlich, Dubinin-Radushkevich (DR) and Temkin. Linearized
      forms of the characteristic parameters were obtained in each case. The models
      that best fit the experimental data were Langmuir TI and Temkin with R(2) >=0.98.
      The regression best fits followed the sequence: Langmuir TI = Temkin > DR >
      LangmuirTII > Freundlich. The microporosity determined by adsorption of CO2 at
      273 K with a single term DR regression presented R(2) > 0.98. The adsorption of
      acetaminophen may occur in specific sites and also in the basal region. It was
      determined that the adsorption process of acetaminophen on AC in SGF is
      spontaneous (DeltaG <0) and exothermic (-DeltaHads.). Moreover, the area occupied
      by the acetaminophen molecule was calculated with a relative error from 7.8 to
      50%. 

PMID- 24570847
TI  - Spray drying as a strategy for biosurfactant recovery, concentration and storage.
AB  - The objective of this study was to analyze the use of Spray Drying for
      concentration and preservation of biosurfactants produced by Bacillus subtilis
      LBBMA RI4914 isolated from a heavy oil reservoir. Kaolinite and maltodextrin 10DE
      or 20DE were tested as drying adjuvants. Surface activity of the biosurfactant
      was analyzed by preparing dilution x surface activity curves of crude
      biosurfactant, crude biosurfactant plus adjuvants and of the dried products,
      after their reconstitution in water. The shelf life of the dried products was
      also evaluated. Spray drying was effective in the recovery and concentration of
      biosurfactant, while keeping its surface activity. Drying adjuvants were required
      to obtain a solid product with the desired characteristics. These compounds did
      not interfere with tensoactive properties of the biosurfactant molecules. The
      dehydrated product maintained its surfactant properties during storage at room
      temperature during the evaluation period (120 days), with no detectable loss of
      activity. 

PMID- 24570848
TI  - Symptomatic cluster headache: a review of 63 cases.
AB  - Cluster headache is a primary headache by definition not caused by any known
      underlying structural pathology. Symptomatic cases have been described, for
      example tumours, dissections and infections, but a causal relationship between
      the underlying lesion and the headache is difficult to determine in many cases.
      The proper diagnostic evaluation of cluster headache is an issue unresolved. The
      literature has been reviewed for symptomatic cluster headache or cluster headache
      like cases in which causality was likely. The review also attempted to identify
      clinical predictors of underlying lesions in order to formulate guidelines for
      neuroimaging. Sixty-three cluster headache or "cluster headache-like"/"cluster
      like headache" cases in the literature were identified which were associated with
      an underlying lesion. A majority of the cases had a non-typical presentation that
      is atypical symptomatology and abnormal examination (including Horner's
      syndrome). A striking finding in this appraisal was that a significant proportion
      of CH cases were secondary to diseases of the pituitary gland or pituitary
      region. Another notable finding was that a proportion of cluster headache cases
      were associated with arterial dissection. Even typical cluster headaches can be
      caused by structural lesions and the response to typical cluster headache
      treatments does not exclude a secondary form. It is difficult to draw definitive
      conclusions from this retrospective review of case reports especially considering
      the size of the material. However, based on this review, I suggest that
      neuroimaging, preferably contrast-enhanced magnetic resonance imaging/magnetic
      resonance angiography should be undertaken in patients with atypical
      symptomatology, late onset, abnormal examination (including Horner's syndrome),
      or those resistant to the appropriate medical treatment. The decision to perform
      magnetic resonance imaging in cases of typical cluster headache remains a matter
      of medical art. 

PMID- 24570849
TI  - Adenosine triphosphate stress dual-source computed tomography to identify
      myocardial ischemia: comparison with invasive coronary angiography.
AB  - PURPOSE: The purpose of this study was to investigate the utility incremental
      diagnostic value of combined assessment with coronary CT angiography (CCTA) and
      myocardial CT perfusion imaging (CTP) using dual-energy technology with an
      Adenosine Triphosphate (ATP) load technique. MATERIALS AND METHODS: Twenty-one
      patients underwent ATP-provocation dual-energy CT and CAG. We compared the
      diagnostic accuracy with CAG, for ischemic region due coronary stenosis by CCTA
      alone and CCTA combined with CTP (Combined CCTA/CTP). RESULTS: All of 21 patients
      CTP images could be evaluated, however 8 CCTA images could not be evaluated by
      calcification and motion artifact, so assessability was 61.9% (13/21) for CCTA
      alone, and 100% for Combined CCTA/CTP. With CAG results as a comparison, the
      sensitivity, specificity, positive predictive value, and negative predictive
      value were, respectively, 83.3% (20/24), 74.4% (29/39), 66.7% (20/30), and 87.8%
      (29/33) for CCTA alone, and 66.7% (16/24), 92.3% (36/39), 84.2% (16/19), and
      81.8% (36/44) for combined CCTA/CTP. The diagnostic accuracy of the two methods
      were 77.8% (49/63) and 82.5% (52/63). CONCLUSION: Dual-energy CT may be a useful
      modality for perfusion assessment and correlated well with the severity of
      stenosis on CAG. This technique may even be of use in cases of severe
      calcification in the coronary artery wall.

PMID- 24570850
TI  - Driving for patients in palliative care-a reality?
AB  - OBJECTIVE: Very little is known about car driving in palliative patients. We have
      asked patients in at home palliative care environments about their driving habits
      during palliative care. METHODS: At admittance to the palliative care program and
      at regular visits the patients were asked a few questions about age, diagnosis,
      sex, driving license, driving, medication and functional status. RESULTS: 23%
      (40) of our studied patients (173) were still driving, and if we included
      patients who responded that they would still consider driving, the corresponding
      figure was 39%. CONCLUSIONS: Our study indicates that the prescribing doctor
      should be well informed about national driving legislation and be prepared to
      discuss driving in combination with heavy opioid medication and tranquilizers
      even with patients in palliative care.

PMID- 24570852
TI  - Investment into the future of microbial resources: culture collection funding
      models and BRC business plans for biological resource centres.
AB  - Through their long history of public service, diverse microbial Biological
      Resource Centres (mBRCs) have made myriad contributions to society and science.
      They have enabled the maintenance of specimens isolated before antibiotics, made
      available strains showing the development and change of pathogenicity toward
      animals, humans and plants, and have maintained and provided reference strains to
      ensure quality and reproducibility of science. However, this has not been
      achieved without considerable financial commitment. Different collections have
      unique histories and their support is often tied to their origins. However many
      collections have grown to serve large constituencies and need to develop novel
      funding mechanisms. Moreover, several international initiatives have described
      mBRCs as a factor in economic development and have led to the increased
      professionalism among mBRCs. 

PMID- 24570853
TI  - Thin films with high surface roughness: thickness and dielectric function
      analysis using spectroscopic ellipsometry.
AB  - An optical surface roughness model is presented, which allows a reliable
      determination of the dielectric function of thin films with high surface
      roughnesses of more than 10 nm peak to valley distance by means of spectroscopic
      ellipsometry. Starting from histogram evaluation of atomic force microscopy (AFM)
      topography measurements a specific roughness layer (RL) model was developed for
      an organic thin film grown in vacuum which is well suited as an example.
      Theoretical description based on counting statistics allows generalizing the RL
      model developed to be used for all non-conducting materials. Finally, a direct
      input of root mean square (RMS) values found by AFM measurements into the
      proposed model is presented, which is important for complex ellipsometric
      evaluation models where a reduction of the amount of unknown parameters can be
      crucial. Exemplarily, the evaluation of a N,N'-dimethoxyethyl-3,4,9,10-perylene
      tetracarboxylic-diimide (DiMethoxyethyl-PTCDI) film is presented, which exhibits
      a very high surface roughness, i.e. showing no homogeneous film at all. 

PMID- 24570851
TI  - Stem cells in a three-dimensional scaffold environment.
AB  - Stem cells have emerged as important players in the generation and maintenance of
      many tissues. However, the accurate in vitro simulation of the native stem cell
      niche remains difficult due at least in part to the lack of a comprehensive
      definition of the critical factors of the stem cell niche based on in vivo
      models. Three-dimensional (3D) cell culture systems have allowed the development
      of useful models for investigating stem cell physiology particularly with respect
      to their ability to sense and generate mechanical force in response to their
      surrounding environment. We review the use of 3D culture systems for stem cell
      culture and discuss the relationship between stem cells and 3D growth matrices
      including the roles of the extracellular matrix, scaffolds, soluble factors, cell
      cell interactions and shear stress effects within this environment. We also
      discuss the potential for novel methods that mimic the native stem cell niche in
      vitro as well as the current associated challenges. 

PMID- 24570854
TI  - Will women soon outperform men in open-water ultra-distance swimming in the
      'Maratona del Golfo Capri-Napoli'?
AB  - This study investigated the change in sex differences across years in ultra
      distance swimming performances at the 36-km 'Maratona del Golfo Capri-Napoli'
      race held from 1954 to 2013. Changes in swimming performance of 662 men and 228
      women over the 59-year period were investigated using linear, non-linear and
      hierarchical regression analyses. Race times of the annual fastest swimmers
      decreased linearly for women from 731 min to 391 min (r (2)  = 0.60, p < 0.0001)
      and for men from 600 min to 373 min (r (2)  = 0.30, p < 0.0001). Race times of
      the annual top three swimmers decreased linearly between 1963 and 2013 for women
      from 736.8 +/- 78.4 min to 396.6 +/- 4.5 min (r (2)  = 0.58, p < 0.0001) and for
      men from 627.1 +/- 34.5 min to 374.1 +/- 0.3 min (r (2)  = 0.42, p < 0.0001). The
      sex difference in performance for the annual fastest decreased linearly from
      39.2% (1955) to 4.7% (2013) (r (2)  = 0.33, p < 0.0001). For the annual three
      fastest competitors, the sex difference in performance decreased linearly from
      38.2 +/- 14.0% (1963) to 6.0 +/- 1.0% (2013) (r (2)  = 0.43, p < 0.0001). In
      conclusion, ultra-distance swimmers improved their performance at the 'Maratona
      del Golfo Capri-Napoli' over the last ~60 years and the fastest women reduced the
      gap with the fastest men linearly from ~40% to ~5-6%. The linear change in both
      race times and sex differences may suggest that women will be able to achieve
      men's performance or even to outperform men in the near future in an open-water
      ultra-distance swimming event such as the 'Maratona del Golfo Capri-Napoli'. 

PMID- 24570855
TI  - An optical interferometric technique for assessing ozone induced damage and
      recovery under cumulative exposures for a Japanese rice cultivar.
AB  - Exposure to ozone (O3) causes reduction both in the growth and yield of rice
      (Oriza sativa L.). Commonly used Chlorophyll fluorescent measurements are not
      sensitive enough for short term exposure of O3 aiming an immediate assessments.
      Such a conventional method typically needs exposure over a few days to detect the
      influence. As an alternative method, we proposed a novel non-invasive, robust,
      real-time, optical Statistical Interferometric Technique (SIT) to measure growth
      at an accuracy of 0.1 nm with a commonly consumed Japanese rice cultivar,
      Koshihikari. In the present study, we have conducted a repetitive O3 exposure
      experiment for three days under three different concentrations of 0 nl l(-1)
      (control), 120 nl l(-1), and 240 nl l(-1), to investigate the damage and recovery
      strengths. As a measure to assess the effect and recovery from three consecutive
      day exposures of O3, we measured the elongation rate (nm mm(-1) sec(-1)) every
      5.5 sec for 7 hours, and it revealed nanometric elongation rate fluctuations or
      Nanometric Intrinsic Fluctuations (NIF). Comparing the standard deviation (SD) of
      normalized nanometric intrinsic fluctuations (NNIF), which was normalized by that
      before the exposure, we found that drastic reductions under both 120 nl l(-1) and
      240 nl l(-1) O3 concentrations. Reduction percentages were large under high O3
      concentration of 240 nl l(-1) indicating the possibility of irreversible effect.
      However exposure to 120 nl l(-1) of O3 showed recovery on the 2(nd) and 3(rd)
      days. While SIT did reveal immediate effect based on an observation for a few
      hours, the visible foliar effect could be observed only after a week. Hence, the
      technique could provide a way for fast assessment of effect and recovery due to
      cumulative exposure of O3 and hence the tolerance as well as the vitality of
      plant. 

PMID- 24570856
TI  - Comparison of in vitro acaricidal effects of commercial preparations of
      cypermethrin and fenvalerate against Rhipicephalus (Boophilus) annulatus.
AB  - Commercially available preparations of cypermethrin (Clinar and Ectomin) and
      fenvalerate (Flytik and Ticomax, 20% E.C) were compared for their acaricidal
      activity against Rhipicephalus (Boophilus) annulatus using adult immersion test.
      Adult tick mortality was higher with Ectomin compared to Clinar. Complete
      eclosion blocking was observed at all the tested concentrations with Ectomin
      while it was observed only at the highest concentration tested for Clinar.
      Compared to Flytik, adult tick mortality was higher with Ticomax at the tested
      concentrations. Complete blocking of hatching of laid ova was observed with
      Flytik at the highest concentration tested. At the manufacture recommended dosage
      of 200 ppm Ectomin elicited 93.37 per cent inhibition of fecundity, while it was
      91.7 per cent for Clinar. For fenvalerate, the recommended concentration was 1200
      ppm at which Ticomax showed 86 per cent and Flytik produced 80.05 per cent
      inhibition of fecundity respectively. 

PMID- 24570857
TI  - Comparative studies on genital infections and antimicrobial susceptibility
      patterns of isolates from camels (Camelus dromedarius) and cows (Bos indicus) in
      Maiduguri, north-eastern Nigeria.
AB  - A total of 160 genitalia of Camels and cows were investigated in Maiduguri, north
      eastern Nigeria to compare bacterial isolates and the antibacterial
      susceptibilities of some of the isolates. Streptococcus (Str.) pyogenes (31%),
      Escherichia (E.) coli (24%) and Staphylococcus (S.) aureus (20%) were the most
      common vaginal bacterial isolates in camels; while E. coli (73%), Str. pyogenes
      (18%) and S. aureus (11%) were the most frequent isolates in the cows. Of the 78
      uterine isolates recovered in this study, E. coli was the most prominent in
      camels (8%) and cows (54%). The overall weight of genital infection in all camels
      and cows examined was highest (P < 0.05) with E. coli (79%), but there was no
      difference (P > 0.05) between vaginal and uterine bacterial isolates from camels
      and cows in this study. The Relative Risk (RR) for an infection of the vagina
      with E coli (3.04, 95% Confidence Interval (CI): 2.104 to 4.398, P < 0.0001) is
      more in cows compared to the camel, but the RR for vaginal infection with S.
      aureus and Str. pyogenes were lower in cows compared to Camels. The E. coli and
      S. aureus isolates were highly susceptible to the antimicrobial agents tested.
      Therefore effective management of reproductive disorders associated with these
      pathogens can be achieved with proper use of these antimicrobial agents in these
      animal species. 

PMID- 24570858
TI  - Initial experience with total thoracoscopic ablation.
AB  - BACKGROUND: Recently, a hybrid surgical-electrophysiological (EP) approach for
      confirming ablation lines in patients with atrial fibrillation (AF) was
      suggested. The aim of this approach was to overcome the limitations of current
      surgery- and catheter-based techniques to yield better outcomes. METHODS: Ten
      consecutive patients with AF underwent total thoracoscopic ablation (TTA)
      following transvenous catheter EP ablation (residual gap and cavotricuspid
      isthmus [CTI] ablation). Holter monitoring was performed 6 months
      postoperatively. RESULTS: Ten patients (90% with persistent AF) underwent
      successful hybrid procedures, and there was no in-hospital mortality. An EP study
      was performed in 8 patients and showed that successful antral ablation in all
      pulmonary veins was achieved in 7 of them. The median follow-up duration was 7.63
      months (range, 6.7 to 11.6 months). Nine patients underwent Holter monitoring 6
      months postoperatively, and the results indicated an underlying sinus rhythm
      without AF, atrial flutter, or atrial tachycardia lasting more than 30 seconds in
      all of the patients. There was no recurrence of AF during follow-up. CONCLUSION:
      A hybrid approach that consists of TTA followed by transvenous catheter EP
      ablation (residual gap and CTI ablation) yielded excellent outcomes in our
      patient population. A hybrid approach should be considered in patients with a
      high risk of AF recurrence.

PMID- 24570859
TI  - Influence of radiologically evident residual intimal tear on expansion of
      descending aorta following surgery for acute type I aortic dissection.
AB  - BACKGROUND: Although a residual intimal tear may contribute to the dilatation of
      the descending aorta following surgical repair of acute type I aortic dissection
      (AD), its causal relationship has not been elucidated by clinical data due to the
      limited resolution of imaging modalities. METHODS: This study enrolled 41
      patients (age, 55.2+/-11.9 years) who were evaluated with dual-source computed
      tomography (CT) imaging of the whole aorta in the setting of the surgical repair
      of acute type I AD. Logistic regression models were used to determine the
      predictors of a composite of the aortic aneurysm formation (diameter >55 mm) and
      rapid aortic expansion (>5 mm/yr). RESULTS: On initial CT, a distal re-entry tear
      was identified in 9 patients. Two patients failed to achieve proximal tear
      exclusion by the surgery. Serial follow-up CT evaluations (median, 24.6 months;
      range, 6.0 to 67.2 months) revealed that 14 patients showed rapid expansion of
      the descending aorta or aortic aneurysm formation. A multivariate analysis
      revealed that the residual intimal tear (odds ratio [OR], 4.31; 95% confidence
      interval [CI], 1.02 to 19.31) and the patent false lumen in the early
      postoperative setting (OR, 4.64; 95% CI, 0.99 to 43.61) were predictive of the
      composite endpoint. CONCLUSION: The presence of a residual intimal tear following
      surgery for acute type I AD adversely influenced the expansion of the descending
      aorta.

PMID- 24570861
TI  - Cost-Effectiveness of Carotid Endarterectomy versus Carotid Artery Stenting for
      Treatment of Carotid Artery Stenosis.
AB  - BACKGROUND: Symptomatic or asymptomatic patients with significant carotid artery
      stenosis (range, 70% to 99%) generally undergo either carotid artery
      endarterectomy (CEA) or carotid artery stenting (CAS) to prevent stroke. In this
      study, we evaluated the cost effectiveness of these two treatment modalities.
      METHODS: A total of 47 patients (mean age, 67.1+/-9.1 years; male, 87.2%)
      undergoing either CEA (n=28) or CAS (n=19) for the treatment of significant
      carotid artery stenosis were enrolled in this study. Hospitalization costs were
      subdivided into three parts, namely pre-procedure, procedure and resource, and
      post-procedure costs. RESULTS: Total hospitalization costs were similar in both
      groups of CEA and CAS (6,377 thousand won [TW] vs. 6,703 TW, p=0.255); however,
      the total cost minus the pre-procedure cost was higher in the CAS group than in
      the CEA group (4,948 TW vs. 5,941 TW, p<0.0001). The pre-procedure cost of the
      CEA group was higher than that of the CAS group (1,429 TW vs. 762 TW, p<0.0001).
      However, the procedure and resource cost was higher in the CAS group because the
      resource cost was approximately three times higher in the CAS group than in the
      CEA group. The post-procedure cost was higher in the CEA group because hospital
      stays were approximately two times longer. CONCLUSION: The total hospitalization
      cost was not different between the CEA and the CAS groups. The pre-procedure cost
      was high in the CEA group, but the cost from procedure onset to discharge,
      including the resource cost, was significantly lower in this group.

PMID- 24570860
TI  - The Prognosis According to Patterns of Mediastinal Lymph Node Metastasis in
      Pathologic Stage IIIA/N2 Non-Small Cell Lung Cancer.
AB  - BACKGROUND: The aim of this study is to evaluate prognostic factors for survival
      in pathologic stage IIIA/N2 non-small-cell lung cancer (NSCLC), to identify the
      prognostic significance of the metastatic patterns of mediastinal lymph nodes
      (MLNs) relating to survival and to recurrence and metastasis. METHODS: A total of
      129 patients who underwent radical resection for pathologic stage IIIA-N2 NSCLC
      from July 1998 to April 2011 were retrospectively reviewed. The end points of
      this study were rates of loco-regional recurrence and distant metastasis, and
      survival. RESULTS: The overall 5-year survival rate was 47.4%. A univariate
      analysis showed that age, pathologic T stage, and adjuvant chemotherapy were
      significant prognostic factors, while in multivariate analysis, pathologic T
      stage and adjuvant chemotherapy were significant prognostic factors. The
      metastasis rate was higher in patients with multistation N2 involvement and with
      more than 3 positive MLNs. Further, non-regional MLN metastasis was associated
      with a higher loco-regional recurrence rate. CONCLUSION: Pathologic T stage and
      adjuvant chemotherapy were independent prognostic factors for long-term survival
      in pathologic stage IIIA/N2 NSCLC. The recurrence and the metastasis rate were
      affected by the metastatic patterns of MLNs. These results may be helpful for
      planning postoperative therapeutic strategies and predicting outcomes.

PMID- 24570862
TI  - A retrospective clinical study: complications of totally implanted central venous
      access ports.
AB  - BACKGROUND: When managing patients who require repeated venous access, gaining a
      viable intravenous route has been problematic. To improve the situation, various
      studies on techniques for venous access have been conducted. The aim of this
      study is to evaluate the clinical results of complications following totally
      implanted central venous access port (TICVAP) insertion. METHODS: A retrospective
      analysis was conducted on 163 patients, from December 2008 to March 2013. The
      occurrence of complications was studied in three separate periods of catheter
      use: the intraoperative period, postoperative period, and period during the
      treatment. RESULTS: A total of 165 cases of TICVAP insertions involving 156
      patients were included in the final analysis. There were 35 complications (21%)
      overall. Among these, 31 cases of complications (19%) occurred during the
      treatment period and the other 4 cases were intraoperative and postoperative
      complications (2%). There were no statistically significant differences in age
      and gender of the patients between the two groups to be risk factors (p=0.147,
      p=0.08). Past history of chemotherapy, initial laboratory findings, and the
      locations of TICVAP insertion also showed no statistical significance as risk
      factors (p>0.05). CONCLUSION: Because the majority of complications occurred
      after port placement and during treatment, meticulous care and management and
      appropriate education are necessary when using TICVAPs.

PMID- 24570863
TI  - Abnormal origin of the left subclavian artery from the left pulmonary artery in a
      patient with double outlet right ventricle.
AB  - Anomalous aortic origin of the left subclavian artery (LSCA) from the left
      pulmonary artery (LPA) is a rare congenital cardiac malformation. We describe a
      case of LSCA from the LPA via ductus arteriosus in association with a double
      outlet right ventricle, which never has been reported previously in Korea. 

PMID- 24570865
TI  - Surgical repair of retrograde type a aortic dissection after thoracic
      endovascular aortic repair.
AB  - It is expected that the stent graft will become an alternative method for
      treating aortic diseases or reducing the extent of surgery; therefore, thoracic
      endovascular aortic repair has widened its indications. However, it can have rare
      but serious complications such as paraplegia and retrograde type A aortic
      dissection. Here, we report a surgical repair of retrograde type A aortic
      dissection that was performed after thoracic endovascular aortic repair. 

PMID- 24570864
TI  - Surgical management of recurrent leiomyosarcoma in heart.
AB  - Leiomyosarcoma may occur anywhere in the body but rarely occurs in the heart or
      great vessels. Leiomyosarcoma may be managed by surgical resection with or
      without chemotherapy or radiotherapy. Owing to the high rate of metastasis and
      poor prognosis, a definitive treatment modality for leiomyosarcoma has not yet
      been suggested. This case study reports the surgical management of the recurrent
      leiomyosarcoma of the heart and the great vessels in a 63-year-old woman. 

PMID- 24570866
TI  - Phlegmasia cerulea dolens after coronary artery bypass surgery: what should we
      know.
AB  - Phlegmasia cerulea dolens (PCD) is one of the most critical disorders of acute
      deep vein thrombosis in that it can cause permanent disability secondary to the
      compartment syndrome. Although several etiological factors have been proposed,
      PCD after coronary artery bypass surgery is extremely rare and its definitive
      pathophysiology is still under debate. We herein present a case of PCD that
      resulted in the compartment syndrome after coronary artery bypass surgery. Early
      recognition and decompression of PCD are crucial for saving the affected limbs. 

PMID- 24570867
TI  - Primary Ewing's Sarcoma of the Lung.
AB  - Most cases of Ewing's sarcoma are reported in the bone, and extraosseous Ewing's
      sarcoma is an extremely rare disease. Here, we report a rare case of primary
      pulmonary Ewing's sarcoma in a patient with hemoptysis. The patient underwent
      right upper lung lobe lobectomy with adjuvant chemotherapy and radiation therapy
      and has been free of recurrent disease for 4 years. 

PMID- 24570868
TI  - Bronchioloalveolar carcinoma in a juvenile rhadomyosarcoma patient.
AB  - Primary tumors of the lung are uncommon in pediatric patients, particularly
      bronchioloalveolar carcinoma (BAC). An 11-year-old female suffering from back
      pain for 1 month was referred to Seoul St. Mary's Hospital for treatment of a
      pathologic fracture of the lumbar spine. Comprehensive evaluation disclosed
      numerous pulmonary metastases of rhabdomyosarcoma (stage IV). During
      chemotherapy, most of the lung lesions regressed, with the exception of two
      nodules. Wedge resections, intended for diagnosis and cure, yielded a histologic
      diagnosis of BAC. 

PMID- 24570869
TI  - Mixed squamous cell and glandular papilloma of the lung in a 64-year-old woman.
AB  - Mixed squamous cell and glandular papilloma of the lung is an extremely rare
      benign epithelial tumor showing a mixture of squamous and glandular epithelium.
      Here, we report a case of mixed squamous cell and glandular papilloma that
      presented as a solitary nodule in the left lower lobe of a 64-year-old woman.
      Chest computed tomography demonstrated a lobulated mass in the basal segment of
      the left lower lobe. The patient underwent a lobectomy under the suspicion of
      lung malignancy. The histopathological diagnosis was mixed squamous cell and
      glandular papilloma. 

PMID- 24570870
TI  - Primary epithelial myoepithelial lung carcinoma.
AB  - Primary epithelial-myoepithelial carcinoma (EMC) of the lung is an extremely rare
      neoplasm that originates from submucosal bronchial glands and has been found in
      the salivary glands, breast tissue, and sweat glands. However, only a few cases
      in the respiratory tract have been identified. In the literature, most pulmonary
      EMCs have been reported to have developed endobronchially although a few EMC
      cases have been presented as intraparenchymatous tumors. We have identified a
      case of primary EMC that developed in the peripheral lung parenchyma. 

PMID- 24570871
TI  - Metastatic pulmonary ameloblastoma misdiagnosed as primary squamous cell
      carcinoma preoperatively.
AB  - Ameloblastomas are rare odontogenic epithelial tumors that occur mainly in the
      mandible. Despite their benign histologic appearance, they are locally aggressive
      with a high recurrence rate. However, a metastasizing ameloblastoma has been
      rarely reported. According to the current World Health Organization
      classification system, the definitive diagnosis of metastasizing ameloblastoma
      can only be carried out in retrospect, after the event of metastasis. This case
      report describes a patient with metastatic pulmonary ameloblastoma, 17 years
      after the surgical excision of an odontogenic tumor, preoperatively misdiagnosed
      as primary squamous cell carcinoma. 

PMID- 24570872
TI  - Treatment of large arteriovenous malformation in right lower limb.
AB  - A 10-year-old boy with arteriovenous malformation (AVM) of the right lower limb
      was scheduled for an amputation of the affected limb. Limb amputation was
      necessary because of the ineffectiveness of previous sclerotherapy and the rapid
      progression of AVM causing pain and heart failure. Right hip disarticulation was
      considered the best option to improve his quality of life. To prevent congestive
      heart failure and uncontrollable hemorrhage during surgery, the disarticulation
      was done under a partial cardiopulmonary bypass. The patient underwent surgery
      successfully without complications. 

PMID- 24570873
TI  - Successful Endovascular Management of Intraoperative Graft Limb Occlusion and
      Iliac Artery Rupture Occurred during Endovascular Abdominal Aortic Aneurysm
      Repair.
AB  - For high-risk patients, endovascular aortic aneurysm repair (EVAR) is a good
      option but may lead to serious complications, which should be addressed
      immediately. A 75-year-old man with a history of abdominal surgery underwent EVAR
      for an aneurysm of the abdominal aorta and iliac arteries. During EVAR, iliac
      artery rupture and graft limb occlusion occurred, and they were successfully
      managed by the additional deployment of an iliac stent graft and balloon
      thrombectomy, respectively. We, herein, report a rare case of the simultaneous
      development of the two fatal complications treated by the endovascular technique.

PMID- 24570875
TI  - Interobserver agreement in using magnifying narrow band imaging system.

PMID- 24570876
TI  - Rectal Retroflexion during Colonoscopy: A Bridge over Troubled Water.

PMID- 24570877
TI  - Metal stenting in benign biliary strictures.

PMID- 24570878
TI  - Recent advances in molecular imaging of premalignant gastrointestinal lesions and
      future application for early detection of barrett esophagus.
AB  - Recent advances in optical molecular imaging allow identification of morphologic
      and biochemical changes in tissues associated with gastrointestinal (GI)
      premalignant lesions earlier and in real-time. This focused review series
      introduces high-resolution imaging modalities that are being evaluated
      preclinically and clinically for the detection of early GI cancers, especially
      Barrett esophagus and esophageal adenocarcinoma. Although narrow band imaging,
      autofluorescence imaging, and chromoendoscopy are currently applied for this
      purpose in the clinic, further adoptions of probe-based confocal laser
      endomicroscopy, high-resolution microendoscopy, optical coherence tomography, and
      metabolomic imaging, as well as imaging mass spectrometry, will lead to detection
      at the earliest and will guide predictions of the clinical course in the near
      future in a manner that is beyond current advancements in optical imaging. In
      this review article, the readers will be introduced to sufficient information
      regarding this matter with which to enjoy this new era of high technology and to
      confront science in the field of molecular medical imaging. 

PMID- 24570879
TI  - Barrett esophagus in Asia: same disease with different pattern.
AB  - Barrett esophagus (BE) is considered to develop as a result of chronic
      gastroesophageal reflux disease (GERD) and to predispose to esophageal
      adenocarcinoma (EAC). However, the disease pattern of BE in Asia differs from
      that observed in the West. For example, in the West, the prevalence rates of BE
      and EAC have progressively increased, whereas although the prevalence rate of
      GERD is increasing in Asia, the prevalence rates of BE and EAC have remained low
      in most Asian countries. GERD, hiatal hernia, old age, male sex, abdominal
      obesity (visceral obesity), smoking, alcohol consumption, and kyphosis are known
      risk factors for BE in Asia, and most Asian patients have short-segment BE.
      Helicobacter pylori infection is more prevalent in Asia than in the West. We
      suggest larger studies with a prospective design be conducted to elaborate
      further the different patterns of BE in Asia. 

PMID- 24570880
TI  - Confocal laser endomicroscopy and molecular imaging in barrett esophagus and
      stomach.
AB  - Detection of premalignant lesions in the upper gastrointestinal tract may
      facilitate endoscopic treatment and improve survival. Despite technological
      advances in white light endoscopy, its ability to detect premalignant lesions
      remains limited. Early detection could be improved by using advanced endoscopic
      imaging techniques, such as magnification endoscopy, narrow band imaging, i
      scanning, flexible spectral imaging color enhancement, autofluorescence imaging,
      and confocal laser endomicroscopy (CLE), as these techniques may increase the
      rate of detection of mucosal abnormalities and allow optical diagnosis. The
      present review focuses on advanced endoscopic imaging techniques based on the use
      of CLE for diagnosing premalignant lesions in Barrett esophagus and stomach. 

PMID- 24570881
TI  - Histopathology in barrett esophagus and barrett esophagus-related dysplasia.
AB  - Pathologic specimens, both biopsies and endoscopic mucosal resections, for
      Barrett esophagus and Barrett-associated dysplasia and malignancy are common for
      pathologists in North America, and the incidence in South Asian countries seems
      to be increasing. Dysplasia and malignancy arising in intestinalized gastric-type
      mucosa raises issues in the interpretation of dysplasia and the evaluation of the
      depth of invasion of malignancies that are not seen in squamous dysplasia and
      squamous cell carcinoma. We review the North American approach to these lesions. 

PMID- 24570882
TI  - Barrett esophagus: when to endoscope.
AB  - Increasing interest in identifying an effective strategy for decreasing the
      burden of esophageal adenocarcinoma (EAC) has been fuelled by the rising EAC
      rates worldwide, the morbidity associated with esophagectomy, and the development
      of endoscopic methods for curing early-stage EAC. In the face of this enthusiasm,
      however, we should be cautious about continuing our current evidence-free
      approach to screening and one with unclear benefits and unclear costs to the
      community. The literature is increasingly recognizing that the value of
      traditional endoscopy for screening and surveillance of Barrett esophagus may be
      more limited than initially believed. A better understanding of the risk factors
      for Barrett esophagus and progression to dysplasia and a more individualized risk
      calculation will be useful in defining populations to consider for Barrett
      screening. The development of novel, nonendoscopic screening techniques and of
      less expensive endoscopic techniques holds promise for a cost-effective screening
      and surveillance method to curtail the increasing rates of EAC. 

PMID- 24570883
TI  - Advanced imaging technologies for the detection of dysplasia and early cancer in
      barrett esophagus.
AB  - Advanced esophageal adenocarcinomas arising from Barrett esophagus (BE) are
      tumors with an increasing incidence and poor prognosis. The aim of endoscopic
      surveillance of BE is to detect dysplasia, particularly high-grade dysplasia and
      intramucosal cancers that can subsequently be treated endoscopically before
      progression to invasive cancer with lymph node metastases. Current surveillance
      practice standards require the collection of random 4-quadrant biopsy specimens
      over every 1 to 2 cm of BE (Seattle protocol) to detect dysplasia with the
      assistance of white light endoscopy, in addition to performing targeted biopsies
      of recognizable lesions. This approach is labor-intensive but should currently be
      considered state of the art. Chromoendoscopy, virtual chromoendoscopy (e.g.,
      narrow band imaging), and confocal laser endomicroscopy, in addition to high
      definition standard endoscopy, might increase the diagnostic yield for the
      detection of dysplastic lesions. Until these modalities have been demonstrated to
      enhance efficiency or cost effectiveness, the standard protocol will remain
      careful examination using conventional off the shelf high-resolution endoscopes,
      combined with as longer inspection time which is associated with increased
      detection of dysplasia. 

PMID- 24570884
TI  - Treatment of dysplasia in barrett esophagus.
AB  - Barrett esophagus is recognized as a risk factor for the development of dysplasia
      and adenocarcinoma of the esophagus. Cancer is usually diagnosed at an advanced
      stage with a 5-year survival rate of 15%. Most of these patients present de novo
      and are not part of a surveillance program. Endoscopic screening with improvement
      in recognition of early lesions may change this pattern. In the past, patients
      diagnosed with dysplasia and mucosal cancer were best managed by esophagectomy.
      Endoscopic techniques such as endoscopic mucosal resection and radiofrequency
      ablation have resulted in high curative rates and a shift away from
      esophagectomy. This pathway is supported by the literature review of
      esophagectomies performed for mucosal disease, as well as pathologists'
      interpretation of endoscopic mucosal specimens, which document the low risk of
      lymph node metastasis. The role of endoscopic therapy for superficial submucosal
      disease continues to be a challenge. 

PMID- 24570886
TI  - Observer variability in gastric neoplasm assessment using the vessel plus surface
      classification for magnifying endoscopy with narrow band imaging.
AB  - BACKGROUND/AIMS: Recent studies have demonstrated that magnifying endoscopy with
      narrow band imaging (ME-NBI) facilitates differentiation of early gastric cancer
      from gastric adenoma using vessel plus surface (VS) classification. This study
      estimated the interobserver and intraobserver agreement of endoscopists using the
      Yao VS classification system for the gastric mucosal surface. METHODS: We
      retrospectively reviewed patients who underwent endoscopic submucosal dissection
      or endoscopic mucosal resection, and selected cases in which preoperative ME-NBI
      was conducted. Before testing endoscopists, a 20-minute training module was
      given. Static ME-NBI images (n=47 cases) were presented to seven endoscopists
      (two experts and five trainees) who were asked to assess the images in 20 seconds
      using the Yao VS classification system. After 2 weeks, the endoscopists were
      asked to analyze the images again. The kappa statistic was calculated for
      intraobserver and interobserver variability. RESULTS: The mean kappa for
      intraobserver agreement was 0.69 (experts, 0.74; trainees, 0.64). The mean kappa
      for interobserver agreement was 0.42 (experts, 0.49; trainees, 0.40).
      CONCLUSIONS: We obtained reliable results as assessed by observer variability,
      with only brief training on VS classification. The VS classification appears to
      provide an objective assessment of ME-NBI for trainees who are not familiar with
      ME-NBI.

PMID- 24570885
TI  - Status and literature review of self-expandable metallic stents for malignant
      colorectal obstruction.
AB  - Use of colorectal stents has increased dramatically over the last decades.
      Colorectal stents offer an alternative way to relieve fatal intestinal
      obstruction and can take place of emergency surgery, which associated with
      significant morbidity and mortality and a high incidence of stoma creation, to
      elective resection. Although there remain a few concerns regarding the use of
      stents as a bridge to surgical resection, use of self-expandable metallic stents
      for palliation in patients with unresectable disease has come to be generally
      accepted. Advantages of colorectal stents include acute restoration of luminal
      patency and allowance of time for proper staging and surgical optimization, and
      the well-known disadvantages are procedure-related complications including
      perforation, migration, and stent failure. General indications, procedures, and
      clinical outcomes as well as recent evidences regarding the use of colorectal
      stents will be discussed in this review. 

PMID- 24570887
TI  - Diagnostic yield and therapeutic impact of rectal retroflexion: a prospective,
      single-blind study conducted in three centers.
AB  - BACKGROUND/AIMS: No clear data have been established and validated regarding
      whether rectal retroflexion has an important and therapeutic impact. The aim of
      the present study was to evaluate the diagnostic yield and therapeutic impact of
      rectal retroflexion compared with straight view examination. METHODS: A
      prospective single-blind study was conducted. Consecutive patients evaluated
      between October 2011 and April 2012 were included. RESULTS: A total of 934
      patients (542 women, 58%) were included. The mean age was 57.4+/-14.8 years.
      Retroflexion was successful in 917 patients (98.2%). Distinct lesions in the
      anorectal area were detected in 32 patients (3.4%), of which 10 (1%) were
      identified only on retroflex view and 22 (2.4%) on both straight and retroflex
      views. Of the 32 identified lesions, 16 (50%) were polyps, nine (28.1%) were
      angiodysplasias, six (18.8%) were ulcers, and one (3.1%) was a flat lesion. All
      10 patients (1%) in whom lesions were detected only by rectal retroflexion showed
      a therapeutic impact. CONCLUSIONS: Rectal retroflexion has minimal diagnostic
      yield and therapeutic impact. However, its low rate of major complications and
      the possibility of detecting lesions undetectable by straight viewing justify its
      use.

PMID- 24570888
TI  - Histological Changes in the Bile Duct after Long-Term Placement of a Fully
      Covered Self-Expandable Metal Stent within a Common Bile Duct: A Canine Study.
AB  - BACKGROUND/AIMS: To date, it has been difficult to determine the optimal stenting
      duration of a fully covered self-expandable metal stent (FCSEMS) in a benign
      biliary stricture. The purpose of this study was to identify the
      histopathological changes in a bile duct resulting from long-term placement of a
      FCSEMS. METHODS: An FCSEMS was inserted into the common bile duct of 12 canines,
      and the animals were divided into four groups. Posteuthanasia, necropsy was
      performed to examine the histopathological changes in the bile ducts after 1, 3,
      6, and 9 months. RESULTS: The results of necropsy showed that the covered
      membranes of the FCSEMSs were intact and easily removed from the bile ducts in 11
      of the canines. Severe epithelial hyperplasia of the stented bile duct and
      epithelial ingrowth into the stent occurred in one animal (from the 3-month
      group). On histopathological examination, mild inflammatory changes were observed
      in the stented bile ducts, and there was no significant difference between the
      four groups. Among the 12 animals, five had de novo stricture. CONCLUSIONS: An
      FCSEMS can be inserted into the bile duct without severe histopathological
      changes up until 9 months. However, a de novo stricture and severe epithelial
      hyperplasia relating to the stent insertion might occur.

PMID- 24570889
TI  - Comparison between Midazolam Used Alone and in Combination with Propofol for
      Sedation during Endoscopic Retrograde Cholangiopancreatography.
AB  - BACKGROUND/AIMS: Endoscopic retrograde cholangiopancreatography (ERCP) is an
      uncomfortable procedure that requires adequate sedation for its successful
      conduction. We investigated the efficacy and safety of the combined use of
      intravenous midazolam and propofol for sedation during ERCP. METHODS: A
      retrospective review of patient records from a single tertiary care hospital was
      performed. Ninety-four patients undergoing ERCP received one of the two
      medication regimens, which was administered by a nurse under the supervision of a
      gastroenterologist. Patients in the midazolam (M) group (n=44) received only
      intravenous midazolam, which was titrated to achieve deep sedation. Patients in
      the midazolam pulse propofol (MP) group (n=50) initially received an intravenous
      combination of midazolam and propofol, and then propofol was titrated to achieve
      deep sedation. RESULTS: The time to the initial sedation was shorter in the MP
      group than in the M group (1.13 minutes vs. 1.84 minutes, respectively; p<0.001).
      The recovery time was faster in the MP group than in the M group (p=0.031). There
      were no significant differences between the two groups with respect to frequency
      of adverse events, pain experienced by the patient, patient discomfort, degree of
      amnesia, and gag reflex. Patient cooperation, rated by the endoscopist as
      excellent, was greater in the MP group than in the M group (p=0.046).
      CONCLUSIONS: The combined use of intravenous midazolam and propofol for sedation
      during ERCP is more effective than midazolam alone. There is no difference in the
      safety of the procedure.

PMID- 24570890
TI  - A Case of Esophageal Fibrovascular Polyp That Induced Asphyxia during Sleep.
AB  - Esophageal fibrovascular polyps are rare, benign, submucosal tumors of the upper
      digestive tract that usually have an indolent course until the lesion attains a
      very large size. The most frequent complaints associated with these tumors
      include dysphagia and foreign body sensation. However, a long pedunculated polyp
      can regurgitate into the pharynx or oral cavity and cause asphyxia and sudden
      death if the larynx is occluded. We describe the case of a 51-year-old man who
      experienced snoring and occasional asphyxia during sleep. Upper endoscopy was
      performed, which indicated the presence of a pedunculated esophageal polyp that
      regurgitated into the vocal cords. The polyp was removed using a polypectomy
      snare and was confirmed to be a fibrovascular polyp based on pathologic
      examination findings. Three months after the excision of the polyp, the patient
      was found to be doing well without any further occurrence of asphyxia or sleep
      disturbances. 

PMID- 24570891
TI  - A Case of Postfundoplication Dysphagia without Symptomatic Improvement after
      Endoscopic Dilatation.
AB  - Laparoscopic fundoplication is a treatment option for gastroesophageal reflux
      disease refractory to medical treatment. When deciding whether or not to undergo
      surgery, patients with refractory gastroesophageal reflux disease and esophageal
      motility disorder need to fully understand the operative procedure, postoperative
      complications, and residual symptoms such as dysphagia, globus sensation, and
      recurrence of reflux. Herein, we report a case of a patient diagnosed with
      gastroesophageal reflux disease and aperistalsis who underwent Nissen (total, 360
      degrees ) fundoplication after lack of response to medical treatment and
      subsequently underwent pneumatic dilatation due to unrelieved postoperative
      dysphagia and globus sensation. 

PMID- 24570892
TI  - Small Bowel Stent-in-Stent Placement for Malignant Small Bowel Obstruction Using
      a Balloon-Assisted Overtube Technique.
AB  - Self-expanding metal stents are a useful therapy to palliate malignant and benign
      luminal gastrointestinal obstruction. Self-expanding metal stents has been widely
      reported for colonic, esophageal, and gastric obstruction. However, endoscopic
      delivery and placement to the small bowel is more challenging and difficult. This
      case illustrates the usefulness and technical advantages of the balloon-overtube
      and enteroscopy technique for the palliative treatment of neoplastic stenosis
      affecting the small intestine. 

PMID- 24570893
TI  - A case of endoscopic removal of a giant appendicolith combined with stump
      appendicitis.
AB  - Stump appendicitis is an acute inflammation of the residual appendix and is a
      rare complication after appendectomy. The physician should be aware of the
      possibility of stump appendicitis in patients with right lower abdominal pain
      after appendectomy so that delayed diagnosis and treatment can be prevented.
      Stump appendicitis is usually treated by surgical resection, and endoscopic
      treatment has not been reported previously. A 48-year-old man who had undergone
      appendectomy 35 years earlier presented to the hospital because of right lower
      quadrant discomfort. A computed tomography scan showed a large stone in the
      residual appendix. Colonoscopic findings revealed a large, smooth, protruding
      lesion at the cecum with a stone inside the appendiceal orifice. Endoscopic
      removal after incision of the appendiceal orifice was performed successfully. 

PMID- 24570894
TI  - Extramedullary plasmacytoma of the pancreas diagnosed using endoscopic
      ultrasonography-guided fine needle aspiration.
AB  - Extramedullary plasmacytoma involves organs outside the bone marrow; however,
      involvement of the pancreas is rare. We recently experienced a case of
      extramedullary plasmacytoma of the pancreas that was diagnosed by endoscopic
      ultrasonography-guided fine needle aspiration (EUS-FNA). EUS-FNA, which has a
      high diagnostic accuracy and an excellent safety profile, is the modality of
      choice for establishing tissue diagnosis. We report a case of extramedullary
      plasmacytoma of the pancreas diagnosed using EUS-FNA. 

PMID- 24570895
TI  - White esophageal mucosa and black gastric mucosa: upper gastrointestinal injury
      due to hydrochloric Acid ingestion.

PMID- 24570898
TI  - HepatoBiliary Surgery and Nutrition - Message from the Editor-in-Chief.

PMID- 24570896
TI  - Neuroendocrine tumors show altered expression of chondroitin sulfate, glypican 1,
      glypican 5, and syndecan 2 depending on their differentiation grade.
AB  - Neuroendocrine tumors (NETs) are found throughout the body and are important as
      they give rise to distinct clinical syndromes. Glycosaminoglycans, in
      proteoglycan (PG) form or as free chains, play vital roles in every step of tumor
      progression. Analyzing tumor samples with different degrees of histological
      differentiation we determined the existence of important alterations in
      chondroitin sulfate (CS) chains. Analysis of the transcription of the genes
      responsible for the production of CS showed a decline in the expression of some
      genes in poorly differentiated compared to well-differentiated tumors. Using anti
      CS antibodies, normal stroma was always negative whereas tumoral stroma always
      showed a positive staining, more intense in the highest grade carcinomas, while
      tumor cells were negative. Moreover, certain specific cell surface PGs
      experienced a drastic decrease in expression depending on tumor differentiation.
      Syndecan 2 levels were very low or undetectable in healthy tissues, increasing
      significantly in well-differentiated tumors, and decreasing in poorly
      differentiated NETs, and its expression levels showed a positive correlation with
      patient survival. Glypican 5 appeared overexpressed in high-grade tumors with
      epithelial differentiation, and not in those that displayed a neuroendocrine
      phenotype. In contrast, normal neuroendocrine cells were positive for glypican 1,
      displaying intense staining in cytoplasm and membrane. Low-grade NETs had
      increased expression of this PG, but this reduced as tumor grade increased, its
      expression correlating positively with patient survival. Whilst elevated glypican
      1 expression has been documented in different tumors, the downregulation in high
      grade tumors observed in this work suggests that this proteoglycan could be
      involved in cancer development in a more complex and context-dependent manner
      than previously thought. 

PMID- 24570899
TI  - Some issues regarding the development of general surgery during the last half
      century.

PMID- 24570897
TI  - Effects of Exposure to Community Violence and Family Violence on School
      Functioning Problems among Urban Youth: The Potential Mediating Role of
      Posttraumatic Stress Symptoms.
AB  - Adolescents who are exposed to violence during childhood are at an increased risk
      for developing posttraumatic stress (PTS) symptoms. The literature suggests that
      violence exposure might also have negative effects on school functioning, and
      that PTS might serve as a potential mediator in this association. The purpose of
      the current study was to replicate and extend prior research by examining PTS
      symptoms as a mediator of the relationship between two types of violence exposure
      and school functioning problems among adolescent youth from an urban setting.
      Participants included a sample of 121 junior high and high school students (M =
      15 years; range = 13-16 years; 60 males, 61 females) within high-crime
      neighborhoods. Consistent with our hypotheses, community violence and family
      violence were associated with PTS symptoms and school functioning problems. Our
      data suggest that community and family violence were indirectly related to school
      functioning problems through PTS symptoms. Findings from this study demonstrate
      that PTS symptoms potentially mediate the relationship between violence exposure
      and school functioning problems across two settings (community and home). Future
      research should further examine protective factors that can prevent youth
      violence exposure as well as negative outcomes related to violence. 

PMID- 24570900
TI  - Diagnosis and treatment of hepatic angiomyolipoma.
AB  - BACKGROUND: Hepatic angiomyolipoma (HAML) is a rare liver tumor. This paper
      summarized the clinical, radiological and pathological features of HAML. METHODS:
      Seventeen cases of HAML were analyzed retrospectively. All patients were
      subjected to surgical resection of tumor, one of which was performed emergency
      surgery because of hemorrhage of tumor. RESULTS: There are 13 females and 4
      males, most of whom were asymptotic except 4 had minimal abdominal discomfort.
      US, CT and/or MRI were taken and corresponding data was comprehensively analyzed
      with other clinical signs and symptoms. Correct preoperative diagnosis was able
      to be achieved in 9 patients. Pathological analysis and immunohistochemistry of
      HMB-45 was used as final diagnosis. All patients were followed up and survived
      without recurrence. CONCLUSIONS: Preoperative diagnosis of HAML can be benefited
      from comprehensive analysis of clinical manifestations. The malignant potential
      and fast growth of tumor suggested surgical removal of tumor while it was
      diagnosed.

PMID- 24570902
TI  - Molecular targeted therapy for biliary tract malignancy: defining the target.

PMID- 24570903
TI  - New evidence of lncRNA role in tumor progression and metastasis.

PMID- 24570904
TI  - Prevention of chronic HBV infection induced hepatocellular carcinoma development
      by using antiplatelet drugs.

PMID- 24570905
TI  - Novel susceptibility loci for hepatocellular carcinoma in chronic HBV carriers.

PMID- 24570907
TI  - Chemoprevention for hepatocellular carcinoma: the role of statins.

PMID- 24570906
TI  - Gallbladder carcinoma post gallbladder-preserving cholecystolithotomy: a case
      report.

PMID- 24570908
TI  - Circulating cancer stem cells: a novel prognostic predictor of hepatocellular
      carcinoma.

PMID- 24570901
TI  - Nutrition of the critically ill - emphasis on liver and pancreas.
AB  - About 25 million individuals undergo high risk surgery each year. Of these about
      3 million will never return home from hospital, and the quality of life for many
      of those who return is often significantly impaired. Furthermore, many of those
      who manage to leave hospital have undergone severe life-threatening
      complications, mostly infections/sepsis. The development is strongly associated
      with the level of systemic inflammation in the body, which again is entirely a
      result of malfunctioning GI microbiota, a condition called dysbiosis, with
      deranged composition and function of the gastrointestinal microbiota from the
      mouth to the anus and impaired ability to maintain intact mucosal membrane
      functions and prevent leakage of toxins-bacterial endotoxins and whole or debris
      of bacteria, but also foods containing proteotoxins gluten, casein and zein and
      heat-induced molecules such as advanced glycation end products (AGEs) and
      advanced lipoxidation end products (ALEs). Markedly lower total anaerobic
      bacterial counts, particularly of the beneficial Bifidobacterium and
      Lactobacillus and higher counts of total facultative anaerobes such as
      Staphylococcus and Pseudomonas are often observed when analyzing the colonic
      microbiota. In addition Gram-negative facultative anaerobes are commonly
      identified microbial organisms in mesenteric lymph nodes and at serosal
      "scrapings" at laparotomy in patients suffering what is called "Systemic
      inflammation response system" (SIRS). Clearly the outcome is influenced by
      preexisting conditions in those undergoing surgery, but not to the extent as one
      could expect. Several studies have for example been unable to find significant
      influence of pre-existing obesity. The outcome seems much more to be related to
      the life-style of the individual and her/his "maintenance" of the microbiota
      e.g., size and diversity of microbiota, normal microbiota, eubiosis, being highly
      preventive. About 75% of the food Westerners consume does not benefit microbiota
      in the lower gut. Most of it, refined carbohydrates, is already absorbed in the
      upper part of the GI tract, and of what reaches the large intestine is of limited
      value containing less minerals, less vitamins and other nutrients important for
      maintenance of the microbiota. The consequence is that the microbiota of modern
      man has a much reduced size and diversity in comparison to what our Palelithic
      forefathers had, and individuals living a rural life have today. It is the
      artificial treatment provided by modern care, unfortunately often the only
      alternative, which belongs to the main contributor to poor outcome, among them;
      artificial ventilation, artificial nutrition, hygienic measures, use of skin
      penetrating devices, tubes and catheters, frequent use of pharmaceuticals, all
      known to significantly impair the total microbiome of the body and dramatically
      contribute to poor outcome. Attempts to reconstitute a normal microbiome have
      often failed as they have always been undertaken as a complement to and not an
      alternative to existing treatment schemes, especially treatments with
      antibiotics. Modern nutrition formulas are clearly too artificial as they are
      based on mixture of a variety of chemicals, which alone or together induce
      inflammation. Alternative formulas, based on regular food ingredients, especially
      rich in raw fresh greens, vegetables and fruits and with them healthy bacteria
      are suggested to be developed and tried. 

PMID- 24570909
TI  - Correlation between 3D-MRCP and intra-operative findings in right liver donors.
AB  - A correct preoperative definition of the hepatic duct confluence anatomy of right
      liver living donors is a pivotal step in determining their candidacy for donation
      and planning the surgery. The purposes of this study are to evaluate the accuracy
      of three-dimensional Magnetic Resonance Cholangiography (3D MRCP) when compared
      with intraoperative cholangiography (IOC) in assessing biliary anatomy and to
      identify imaging characteristics that may help predict the yield of hepatic duct
      orifices in the right liver graft. Twenty consecutive right liver donors were
      imaged with 3D MRCP and IOC. The MRCP and IOC findings were compared, and the
      results confirmed against actual donor anatomy. Three-D MRCP accurately predicted
      the biliary anatomy in 18 of 20 cases. Specificity and positive predictive value
      of 3D MRCP in defining normal biliary anatomy was 100%. In 2 patients, 3D MRCP
      failed to indentify abnormal anatomy. The yield of more than one hepatic duct was
      associated with: (I) The presence of abnormal biliary anatomy, (II) The length of
      the main right hepatic duct, and (III) The presence of an acute angle at the
      confluence of right and left hepatic duct. In conclusion, 3D MRCP reliably
      represents normal biliary anatomy. The presence of anatomical variations
      decreases MRCP sensitivity and makes IOC or duct probing a necessary tool for
      accurately performing the transection of the right hepatic duct. 

PMID- 24570910
TI  - Improvement of nutritional support strategies after surgery for benign liver
      tumor through nutritional risk screening: a prospective, randomized, controlled,
      single-blind clinical study.
AB  - OBJECTIVE: The rising of individualized therapy requires nutritional risk
      screening has become a major topic for each particular disease, yet most of the
      screenings were for malignancies, less for benign diseases. There is no report on
      the screening of patients with benign liver tumors postoperatively. We aim to
      evaluate the nutritional support strategies post operation for benign liver
      tumors through nutritional risk screening. METHODS: In this prospective,
      randomized, controlled study, 95 patients who underwent hepatectomy for benign
      tumors were divided into two groups. Fifty patients in the control group were
      given routine permissive underfeeding nutritional supply (75 kJ/kg/d), and 45
      patients in the experimental group were given lower energy (42 kJ/kg/d) in
      accordance of their surgical trauma. Routine blood tests, liver/kidney function
      were monitored before surgery and at the day 1, 3, 5, 9 after surgery, patients
      were observed for the time of flatus, complications, length of hospitalization
      (LOH), nutrition-related costs, and other clinical parameters. This completed
      study is registered with Clinicaltrials.gov, number NCT01292330. RESULTS: The
      nutrition-related expenses (494.0+/-181.0 vs. 1,514.4+/-348.4 RMB, P<0.05) and
      the total hospital costs (18,495.2+/-4735.0 vs. 21,432.7+/-8,291.2 RMB, P<0.05)
      for patients in the experimental group were significantly lower than those in the
      control group. Meanwhile, the lowered energy supply after the surgeries did not
      have adverse effects on clinical parameters, complications, and LOH. CONCLUSIONS:
      Patient with benign liver tumors can adopt an even lower postoperative
      nutritional supply that close to that for mild non-surgical conditions, and lower
      than the postoperative permissive underfeeding standard.

PMID- 24570912
TI  - Targeted agents: how can we improve the outcome in biliary tract cancer?

PMID- 24570911
TI  - Liver transplantation for hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is the most common primary tumor of the liver and
      is considered an aggressive tumor with mean survival estimated between 6 and 20
      months. Hepatitis B and C are the most common etiologies. Pathological,
      laboratory and radiologic imaging all aid in diagnosis but much controversy
      exists in the utilization of any given modality. Many treatment options exist for
      management of HCC, each has its own limitation. Liver transplantation offers the
      most reasonable expectation for curative treatment while simultaneously removing
      the burden of the diseased liver. Still, advancements in the field have thus far
      not yet matched its potential, although new immunosuppressive and chemotherapy
      regimen may allow transplantation to push the envelope once again. 

PMID- 24570913
TI  - Do statins reduce the risk of hepatocellular carcinoma in patients with chronic
      hepatitis B?

PMID- 24570914
TI  - Chemoprevention and novel therapy for hepatocellular carcinoma associated with
      chronic hepatitis B virus infection.

PMID- 24570915
TI  - Saving private healthcare after the verdict.

PMID- 24570917
TI  - Angiogenic factors in chronic liver diseases: the effects on hepatic progenitor
      cells.

PMID- 24570916
TI  - Peripheral primitive neuroectodermal tumors arising in the pancreas: the first
      case report in Asia and a review of the 14 total reported cases in the world.
AB  - OBJECTIVE: To discuss the diagnosis and treatment of peripheral primitive
      neuroectodermal tumors of the pancreas based on our case and all the cases in the
      world. METHODS: The first case of peripheral primitive neuroectodermal tumors of
      the pancreas in Asia was preliminarily reported by our group in 2006. The patient
      underwent three operations for the primary tumor and recurrences over 41 months
      prior to the patient's death in November 2007. All 14 reported cases of
      pancreatic PNETs in the world were analyzed. The corresponding literatures on its
      diagnosis and treatment of were reviewed. RESULTS: A 13 year-old female patient
      was diagnosed with pancreatic PNETs by the clinical, microscopic,
      immunohistochemical features, and cytogenetic analysis after the resection of the
      tumor located in the uncinate process of the pancreas at PUMC Hospital. During
      the follow-up course, radiotherapy and chemotherapy were given after the first
      operation. Two additional operations were performed 10 months and 25 months after
      the first one, respectively, because of tumor recurrence. The patient died 41
      months after the initial diagnosis with the recurrence and metastasis that were
      not suitable for a further surgery. Primitive neuroectodermal tumors of the
      pancreas are extremely rare. A review of the world's literature on this tumor
      identified fourteen cases with a mean survival time of 12 months (ranging from 6
      to 50 months). These patients often have no specific clinical symptoms, but most
      do present with abdominal pain and/or jaundice. The diagnosis is established by
      small round tumor cells seen on light microscopy, immunohistochemical features of
      positive P30/32(MIC2) with at least two positive neuronal markers., and
      cytogenetic analysis showing characteristic translocation of t[11;22][q24;q12].
      Since pancreatic PNETs are highly aggressive, early diagnosis, immediate surgical
      resection and re-resection if possible, early radiotherapy and chemotherapy and
      close follow-up are required. CONCLUSIONS: Peripheral primitive neuroectodermal
      tumors can arise in pancreas. The diagnosis and treatment should be made as early
      as possible, aggressive surgeries for the primary and recurrences may help to
      improve the prognosis.

PMID- 24570918
TI  - Vascular endothelial growth factors in progenitor cells mediated liver repair.

PMID- 24570920
TI  - Effects of EZH2 gene on the growth and migration of hepatocellular carcinoma
      HepG2 cells.
AB  - OBJECTIVE: To investigate the effects of EZH2 gene on the growth and migration of
      hepatocellular carcinoma HepG2 cell in vitro and in vivo. METHODS: EZH2 shRNA
      plasmid vectors were constructed and transfected into HepG2 cells. A model of
      EZH2 gene-silencing HepG2 cell lines was constructed, and the experimental cells
      were classified into 3 groups: HepG2 blank control group, HepG2-V vector control
      group and HepG2-EZH2 (-) group. The mRNA and protein expressions of EZH2 in these
      three cells were detected by real-time fluorogenic quantitative PCR and Western
      blotting, respectively. Cell proliferation was analyzed by MTT assay. Cells were
      inoculated subcutaneously in nude mice, and the growth of tumor cells in vivo was
      observed. Transwell chamber assay was performed to observe any change in the
      migration ability of cells. RESULTS: The mRNA expression of HepG2 and HepG2-V was
      100% and (95.27+/-10.87)%, respectively. Compared with the control group, the
      mRNA level of HepG2-EZH2 (-) were significantly decreased to (20.55+/-13.21)%
      (P<0.001). Similarly, the EZH2 protein expression were inhibited in HepG2-EZH2 (
      ) cells. The inhibition rate of tumor growth was 36.3% in vitro and 52.5% in
      vivo. The migration rate of the HepG2-EZH2 (-) group [(7.15+/-1.13)%] was
      significantly lower than those in the HepG2 group [(14.57+/-4.32)%] and the HepG2
      V group [(15.21+/-5.22)%], with significant differences (both P<0.05).
      CONCLUSIONS: EZH2 silencing can effectively inhibit the proliferation and growth
      of HepG2 cells in vitro and in vivo and inhibit cell migration. Therefore, the
      EZH2 gene may be a novel target for the treatment of liver cancer.

PMID- 24570919
TI  - Expression of vascular endothelial growth factors and their receptors by hepatic
      progenitor cells in human liver diseases.
AB  - Hepatic stem/progenitor cells (HPCs) are stem cells residing in the most
      peripheral branches of the biliary tree; these cells are able to differentiate
      towards mature hepatocyte or mature cholangiocyte; moreover in normal conditions,
      they are mostly quiescent cells. HPC activation has been involved in the
      progression of chronic parenchymal diseases (chronic viral hepatitis) and chronic
      biliary diseases (such as Primary Biliary Cirrhosis: PBC) and in the occurrence
      of intrahepatic cholangiocarcinoma. The HPCs participate in the repair of liver
      damage either through the replacement of dead cells or by driving fundamental
      repair processes, including fibrosis and angiogenesis. Little information exists
      regarding the expression of VEGF by HPC in the course of liver non-malignant
      pathologies. In this study, we evaluated: (I) the presence of HPCs in PBC and HCV
      related Cirrhosis (HCV-C) samples, and (II) the expression of VEGFs and VEGF-Rs
      in PBC and HCV-C samples. Our results showed (I) PBC samples presented a more
      extensive expansion of HPC population in comparison with those of HCV-C samples;
      (II) PBC samples showed a more extensive angiogenesis if compared to HCV-C; and
      (III) PBC samples were characterized by an increased expression of VEGF-A and
      VEGF-C if compared to HCV-C and the number of HPCs expressing VEGFs was
      correlated with the extension of ductular reaction and angiogenesis. The role of
      VEGFs in the expansion of HPC niche could have important implication in the
      management of fibrogenic processes and carcinogenesis. 

PMID- 24570921
TI  - Selection of patients of hepatocellular carcinoma beyond the Milan criteria for
      liver transplantation.
AB  - The Milan criteria have been proven to be reliable and easily applicable in
      selection of patients with small unresectable hepatocellular carcinomas for liver
      transplantation. It has been repeatedly shown that patients who met these
      criteria had a 5-year survival of over 70% after transplantation. Such a result
      is remarkably good for an otherwise incurable malignancy. The main disadvantage
      of this set of criteria is that it is rather restrictive. Following it
      religiously denies transplantation to many patients who have tumor stage slightly
      more advanced. There have been many attempts to extend the criteria to include
      tumors with larger sizes (as in the UCSF criteria) or with a larger number (as in
      the Kyoto criteria). Alpha-fetoprotein and PIVKA-II, two biological markers in
      more aggressive tumors, have also been employed in the selection of patients, and
      biopsies have been used by the University of Toronto to determine tumor
      aggressiveness before deciding on transplantation. Patients with tumors beyond
      the Milan criteria yet not of a high grade have been accepted for transplantation
      and their survival is comparable to that of transplant recipients who were within
      the Milan criteria. Preoperative dual-tracer ((11)C-acetate and FDG) positron
      emission tomography has been used to determine tumor grade, and transarterial
      chemoembolization has been used to downstage tumors, rendering them meeting the
      Milan criteria. Patients with downstaged tumors have excellent survival after
      transplantation. Partial response to chemical treatment is a reflection of less
      aggressive tumor behavior. Careful selection of patients beyond the Milan
      criteria with the aid of serum tumor marker assay, positron emission tomography
      or tumor biopsy allows transplanting more patients without compromising survival.
      The use of liver grafts either from the deceased or from living donors could thus
      be justified. 

PMID- 24570922
TI  - Nutrition and metabolism in hepatocellular carcinoma.
AB  - Hepatocellular carcinoma is the fifth most common human cancer worldwide, with an
      overall 5-year survival in the range of 10%. In addition to the very substantial
      role of chronic viral hepatitis in causing hepatocellular carcinoma, nutritional
      status and specific nutritional factors appear to influence disease risk. This is
      apparent in the increased risk associated with non-alcoholic hepatic cirrhosis
      occurring in the context of obesity, the metabolic syndrome, and type 2 diabetes.
      Specific nutrients and ingested toxins, including ethanol, aflatoxin,
      microcystins, iron, and possibly components of red meat, also are associated with
      increased hepatocellular carcinoma risk. Other dietary components, including
      omega-3 fatty acids and branched chain amino acids, may have protective effects.
      Recent data further suggest that several metabolic regulatory drugs, including
      metformin, pioglitazone, and statins, may have the potential to decrease the risk
      of hepatocellular carcinoma. The available data on these nutritional and
      metabolic factors in causing hepatocellular carcinoma are reviewed with the goal
      of identifying the strength of current knowledge and directions for future
      investigation. 

PMID- 24570924
TI  - Intraoperative margin re-resection for colorectal cancer liver metastases.
AB  - One of the basic tenets of surgical oncology is the achievement of margin
      negative resection. The importance of surgical margins in hepatic resection for
      colorectal cancer liver metastases (CRCLM) is reflected in the abundance of
      literature written about this topic. However, the definition of the ideal
      surgical margin has evolved in parallel with advances in systemic chemotherapy,
      biologic therapy and surgical technology. A better understanding of the biology
      of liver metastasis is of critical importance in the context of surgical strategy
      for CRCLM. The value of intraoperative margin re-resection to achieve R0 status
      for CRCLM is addressed, taking into consideration current understandings of
      cancer biology. 

PMID- 24570925
TI  - Liver transplantation for hepatocellular carcinoma: are international guidelines
      possible?

PMID- 24570926
TI  - Statins: emerging role in chemoprevention for hepatocellular carcinoma?

PMID- 24570927
TI  - Hepatitis B virus and host factors.

PMID- 24570923
TI  - Regional hepatic therapies: an important component in the management of
      colorectal cancer liver metastases.
AB  - The treatment of colorectal cancer liver metastases (CRLM) has evolved
      significantly in the last 15 years. Currently, complete surgical resection
      remains the only potentially curative option; unfortunately, approximately 80% of
      patients with CRLM are not candidates for complete tumor resection. For patients
      with unresectable CRLM the available treatment options were historically limited;
      however, the development of regional hepatic therapies (RHT) and improvement of
      systemic chemotherapeutic regimens have emerged as viable options to improve
      overall survival and quality of life for this group of patients. The selection,
      sequence and integration of interventions into a multi-modal approach is a
      complex and evolving discipline. In this article, the currently available RHT
      modalities for CRLM are presented as a guide to the options for clinical
      treatment decisions. 

PMID- 24570928
TI  - Profiling HBV integrations in hepatocellular carcinoma.

PMID- 24570929
TI  - DKK1 as a serum biomarker for hepatocellular carcinoma.

PMID- 24570930
TI  - Risk stratification for Hepatitis B treatment in the molecular age.

PMID- 24570931
TI  - The antiapoptotic effects of different doses of beta-carotene in chronic ethanol
      fed rats.
AB  - BACKGROUND: Ethanol consumption might induce hepatic apoptosis and cause liver
      damage. The study was to investigate the effects of different doses of beta
      carotene supplementation on the antioxidant capacity and hepatic apoptosis in
      chronic ethanol-fed rats. METHODS: Rats were divided into 6 groups: C (control
      liquid diet), CLB [control liquid diet with beta-carotene supplementation at 0.52
      mg/kg body weight (BW)/day], CHB (control liquid diet with beta-carotene
      supplementation at 2.6 mg/kg BW/day), E (ethanol liquid diet), ELB (ethanol
      liquid diet with beta-carotene supplementation at 0.52 mg/kg BW/day), and EHB
      (ethanol liquid diet with beta-carotene supplementation at 2.6 mg/kg BW/day).
      After 12 weeks, rats were sacrificed and blood and liver samples were collected
      for analysis. RESULTS: Lipid peroxidation and hepatic cytochrome P450 2E1
      (CYP2E1) expression had increased, and hepatic Fas ligand, caspase-8, cytochrome
      c, caspase-9, and -3 expressions had significantly increased in the E group.
      However, lipid peroxidation and CYP2E1, caspase-9, and -3 expressions were
      significantly lower and Bcl-xL expression was higher in the ELB group. The
      hepatic tumor necrosis factor (TNF)-alpha level, lipid peroxidation, and
      cytochrome c expression were significantly lower and Bcl-2 expression was
      significantly higher in the EHB group. CONCLUSIONS: The results suggest that
      ethanol treatment causes oxidative stress and hepatic apoptosis leading to liver
      injury, and beta-carotene supplementation (0.52 mg/kg BW/day) can prevent ethanol
      induced liver damage by decreasing ethanol-induced oxidative stress and
      inhibiting apoptosis in the liver.

PMID- 24570932
TI  - Probiotic use in preventing postoperative infection in liver transplant patients.
AB  - BACKGROUND: Although liver transplantation has been widely practised, post
      operative bacterial infection is still a frequent complication which contributed
      to an increased risk of fatality. There were studies on preoperative use of
      probiotics for liver transplant patients and acquired reduction in postoperative
      sepsis and wound infection, but the relevant clinical experience with pre- and
      probiotics is still limited. OBJECTIVES: This study is to assess fibre and
      probiotic use aimed at preventing bacterial sepsis and wound complications in
      patients undergoing liver transplantation. STUDY METHODS: There were a total of
      sixty-seven adult patients scheduled for liver transplantation were included in a
      public teaching hospital. From January to December 2011, 34 continuous patients
      following liver transplantation were put on fibre + probiotics. In
      retrospectively, from January to December 2010, 33 continuous patients were
      collected as a control group and they were only received fibre post operation.
      The incidence of bacterial infections was compared in patients receiving either
      fibre and lactobacillus or fibre only. Statistical analysis was performed using
      SPSS 15. The t test, fisher's and chi- square test was used to compare discrete
      variables. RESULTS: In summary, in the analysis of 67 liver transplant
      recipients, 8.8% group A patients developed infections compared to 30.3% group B
      patients. The difference between groups A and B was statistically significant in
      both cases. In addition, the duration of antibiotic therapy was significantly
      shorter in the lactobacillus-group. Wound infection was the most frequent
      infections and enterococci the most frequently isolated bacteria. Fibre and
      lactobacilli were well tolerated in most cases. The operating time, amount of
      intra- and post-operatively transfused units of blood, fresh frozen plasma and
      albumin did not differ significantly between the groups. CONCLUSIONS: Combined
      fibre and probiotics could lower the incidence of bacterial infections and
      shorten the duration of antibiotic therapy following liver transplantation in
      comparison to conventional nutrition. In contrast to antibiotics, it is
      relatively cheap and does not cause resistant strains or serious side effects.

PMID- 24570933
TI  - Prognostic significance of vascular endothelial growth factor expression in
      hepatocellular carcinoma tissue: a meta-analysis.
AB  - BACKGROUND: Vascular endothelial growth factor (VEGF) is considered as a prime
      mediator of angiogenesis, and has been implicated in carcinogenesis and
      metastasis. Various studies examined the relationship between VEGF overexpression
      with the clinical outcome in patients with hepatocellular carcinoma (HCC), but
      yielded conflicting results. METHODS: Electronic databases updated to June 2013
      were searched to find relevant studies. A meta-analysis was conducted with
      eligible studies which quantitatively evaluated the relationship between VEGF
      overexpression and survival of patients with HCC. Survival data were aggregated
      and quantitatively analyzed. RESULTS: We performed a meta-analysis of 14 studies
      that evaluated the correlation between VEGF overexpression and survival in
      patients with HCC. Combined hazard ratios suggested that VEGF overexpression had
      an unfavorable impact on overall survival (OS) [hazard ratio (HR) =1.42, 95%
      confidence interval (CI): 1.42-1.7], but not disease free survival (DFS)
      (HR=1.13, 95% CI: 0.89-1.38) in patients with HCC. No significant heterogeneity
      (P=0.949) was observed among 9 studies for OS, however significant heterogeneity
      (P=0.008) was observed among 11 studies for DFS. CONCLUSIONS: VEGF overexpression
      indicates a poor prognosis for patients with HCC.

PMID- 24570934
TI  - Gas jet transection of liver parenchima: experimental research.
AB  - BACKGROUND: There exists a great variety of liver parenchyma transection
      techniques. The objective of this research is to develop a new method of liver
      transection, and to compare it with the traditional ones. METHODS: An original
      gas jet transection method of biological tissues and the apparatus "Pneumojet" to
      make the method practicable were developed in our institute. Comparison between
      the efficiency of gas jet, water jet, ultrasonic methods of liver transection and
      clamp crushing technique were carried out on 24 mini-pigs. Pringle maneuver was
      not included. RESULTS: The mean blood loss was the smallest in the group of
      animals that had a gas jet transection (3.5+/-0.15 mL/cm(2)) but the highest in
      the clamp crushing technique group (5.5+/-0.46 mL/cm(2)). Indicators
      significantly showed the statistical difference (P<0.001). The transection speed
      was the highest in the Clamp crushing technique group (2.9+/-0.25 cm(2)/min) and
      was credibly higher than in the gas jet (2.4+/-0.16 cm(2)/min), ultrasonic (2.4+/
      0.13 cm(2)/min) and water jet (2.5+/-0.14 cm(2)/min) transection groups. Compared
      with the water jet and ultrasonic methods of liver transection, the original
      method does not have statistically significant distinctions on the basic indexes
      of work. CONCLUSIONS: The research conducted proves high efficiency and safety of
      the gas jet transection method. The gas jet transection, therefore, could be
      recommended for further improvement and clinical application.

PMID- 24570935
TI  - Liver transplantation for unresectable colorectal liver metastasis.

PMID- 24570936
TI  - Magnetic resonance cholangiopancreatography in assessing living liver donors
      biliary anatomy: opportunities and challenges.

PMID- 24570937
TI  - Comparison of high-intensity focused ultrasound therapy and radiofrequency
      ablation for recurrent hepatocellular carcinoma.

PMID- 24570938
TI  - T-tube or no T-tube for bile duct anastomosis in orthotopic liver
      transplantation.

PMID- 24570939
TI  - Multiple disciplinary consensus on perioperative management of overwhelming
      inflammation for patients undergoing liver resection: an interpretation.

PMID- 24570940
TI  - Professor James Garden: my experiences and opinions of laparoscopic surger.

PMID- 24570941
TI  - Professor Timothy Pawlik: what have we achieved in hilar cholangiocarcinoma over
      the past decade?

PMID- 24570942
TI  - Is really full right full left split liver transplantation a valuable tool to
      increase organ availability?

PMID- 24570943
TI  - High-intensity focused ultrasound (HIFU) for the treatment of hepatocellular
      carcinoma: is it time to abandon standard ablative percutaneous treatments?

PMID- 24570944
TI  - Liver transplantation in mainland China: the overview of CLTR 2011 annual
      scientific report.
AB  - China Liver Transplant Registry (CLTR) is the official national liver transplant
      registry in Mainland China that has been authorized by the National Health and
      Family Planning Commission of the People's Republic of China (NHFPC) and serves
      for both regulatory and scientific purposes. The CLTR 2011 annual scientific
      reports released national statistics describing current status of liver
      transplant (LT) in China. This article, as an accompanying document of CLTR 2011
      annual scientific report, provides an overview of scientific results for LT in
      China. Up to December 2011, a total number of 20,877 LT performed during 1980
      2011 in 81 certified transplant centers had been reported to CLTR. Of these
      donated livers, 92.63% were procured from deceased donors (N=19,338) and 7.37%
      were from living donors (N=1,539). In March 2010, the pilot project of the new
      deceased organ donation was initiated. From the initiation of the pilot program
      to the end of 2011, there were 115 LT (0.55% of all LT) using the liver grafts
      from Chinese categories donors. The recipient post-transplant survival had been
      significantly improved over years. The median post-transplant follow-up was 14.74
      months, of which the longest follow-up time was 192.47 months. The 1-year, 3-year
      and 5-year cumulative survival rate for all recipients was 77.97%, 65.38% and
      60.53%, respectively. 

PMID- 24570945
TI  - Serum VEGF level is associated with the outcome of patients with hepatocellular
      carcinoma: a meta-analysis.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is a highly vascular tumor that
      expresses vascular endothelial growth factor (VEGF). Various studies have
      evaluated the prognostic value of VEGF levels in HCC, but yielded conflicting
      results. METHODS: Electronic databases updated to June 2013 were searched to find
      relevant studies. A meta-analysis was conducted with eligible studies which
      quantitatively evaluated the relationship between serum VEGF level and survival
      of patients with HCC. Survival data were aggregated and quantitatively analyzed.
      RESULTS: We performed a meta-analysis of 11 studies that evaluated the
      correlation between serum VEGF level and survival in patients with HCC. Combined
      hazard ratios suggested that serum VEGF level had an unfavorable impact on
      overall survival (OS) [hazard ratio (HR) =1.88, 95% confidence interval (CI):
      1.46-2.30], and disease free survival (DFS) (HR=2.27, 95% CI: 1.55-2.98) in
      patients with HCC. No significant heterogeneity was observed among all studies.
      CONCLUSIONS: Serum high VEGF level indicates a poor prognosis for patients with
      hepatocellular carcinoma.

PMID- 24570948
TI  - Twenty-eight years of repeated relapse of gastrointestinal stromal tumor.

PMID- 24570947
TI  - Perspectives on using des-gamma-carboxyprothrombin (DCP) as a serum biomarker:
      facilitating early detection of hepatocellular carcinoma in China.
AB  - Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related
      deaths in China. Evidence has shown that surgical resection and liver
      transplantation may offer the best potential for treating HCC but are only
      available to patients whose tumors are detected early. Over the past few decades,
      although a series of measures for standardized management of HCC has been
      implemented in China, most patients with HCC in China still present with advanced
      stage disease, thus strategies to screen for and diagnose HCC at an earlier stage
      are urgently needed in China when curable interventions can be offered to achieve
      long-term disease-free survival for patients with HCC. In China, the serum
      biomarker alpha-fetoprotein (AFP) is considered a useful and feasible tool for
      HCC screening and early diagnosis. However, the sensitivity and specificity of
      AFP vary widely, and the total AFP is not always specific, especially when HCC is
      in its early stages. Globally, numerous studies have reported that the
      combination of des-gamma-carboxyprothrombin (DCP) and AFP may have a higher
      sensitivity than AFP alone, and suggested DCP could also be used to assess the
      progression of HCC. However, DCP has not been approved in China until now. Differ
      from most of Western countries, people with HBV infection are the largest
      population at risk of developing HCC China. In order to assess the screening and
      diagnostic value of DCP in Chinese patients with HCC, a first large-scale, multi
      center study was launched in China in 2012, results showed that DCP can help to
      detect HCC in its early stages and facilitate definitive treatment. The clinical
      use of DCP is urgently needed to facilitate early detection of HCC in China. 

PMID- 24570949
TI  - China's expert consensus on laparoscopic liver resection and guidelines on
      surgical procedures: an interpretation.

PMID- 24570946
TI  - Histamine regulation of pancreatitis and pancreatic cancer: a review of recent
      findings.
AB  - The pancreas is a dynamic organ that performs a multitude of functions within the
      body. Diseases that target the pancreas, like pancreatitis and pancreatic cancer,
      are devastating and often fatal to the suffering patient. Histamine and histamine
      receptors (H1-H4HRs) have been found to play a critical role in biliary diseases.
      Accordingly, the biliary tract and the pancreas share similarities with regards
      to morphological, phenotypical and functional features and disease progression,
      studies related the role of H1-H4HRs in pancreatic diseases are important. In
      this review, we have highlighted the role that histamine, histidine decarboxylase
      (HDC), histamine receptors and mast cells (the main source of histamine in the
      body) play during both pancreatitis and pancreatic cancer. The objective of the
      review is to demonstrate that histamine and histamine signaling may be a
      potential therapeutic avenue towards treatment strategies for pancreatic
      diseases. 

PMID- 24570950
TI  - Professor Henri Bismuth: the past, present and future of hepatobiliary surgery.

PMID- 24570951
TI  - Professor Pierce Chow: neo-adjuvant and adjuvant therapy for hepatocellular
      carcinoma-current evidence.

PMID- 24570952
TI  - Splitting liver grafts for two adults: suboptimal grafts or suboptimal matching?
AB  - Liver splitting in order to offer liver transplant to two adult candidates is an
      attractive strategy in order to expand the donor pool, however, results have
      limited the widespread of this option. Some of the most relevant aspects of graft
      allocation and recipient selection are discussed in this editorial, based on the
      most recent Italian experience. 

PMID- 24570953
TI  - Carotenoids and alcoholic liver disease.
AB  - Chronic and excessive consumption of alcohol leads to the development of
      alcoholic liver disease. The depletion of vitamin A is a well-known consequence
      of alcohol consumption, and may be associated with the observed alcohol-induced
      hepatic injury. The provitamin A carotenoid beta-carotene has been demonstrated
      to increase alcohol-induced hepatic injury when given in high doses, while low
      dose supplementation provides protection against hepatic injury. However, it is
      unknown if the hepatoprotective effects of low dose beta-carotene are due to the
      protective actions of beta-carotene itself or if the alterations are due to
      restored vitamin A levels. Future studies are needed to provide further insight
      into the specific mechanisms by which beta-carotene exerts its protective effect.
      Further, supplementation studies utilizing high doses of beta-carotene in the
      presence of alcohol must be done with caution. 

PMID- 24570954
TI  - Eat more carrots? Dampening cell death in ethanol-induced liver fibrosis by beta
      carotene.
AB  - Alcoholic liver disease (ALD) represents one of the principal causes of liver
      damage in humans. Long-term ethanol abuse leads to progressive liver injury and
      tissue remodeling, including steatosis, inflammation, fibrosis, cirrhosis and
      increased risk for hepatocellular carcinoma (HCC) development. Oxidative stress
      and subsequent liver cell death has long been identified as one of the key
      mechanisms during ALD progression, therefore antioxidants may display promising
      treatment options. In this issue of Hepatobiliary Surgery and Nutrition (HBSN),
      Peng et al. demonstrate that oral supplementation with beta-carotene during
      chronic ethanol feeding in rats reduces oxidative stress, apoptotic cell death
      and inflammation. Reducing hepatocyte apoptosis, a major trigger for fibrogenesis
      and tumorigenesis, would make beta-carotene a prospective target for treatment.
      However, before translating the promising findings of Peng and colleagues into
      clinical scenarios, it needs to be determined which cell death pathways,
      including necrosis and necroptosis, are affected by beta-carotene, which liver
      cell populations are targeted by this vitamin A precursor, how specific the
      effects are for ALD in comparison to non-alcoholic steatohepatitis (NASH) or
      other chronic liver diseases, and whether reduced hepatic oxidative stress and
      apoptosis upon beta-carotene supplementation truly relate to beneficial long-term
      consequences with respect to fibrosis, cirrhosis or HCC development. 

PMID- 24570955
TI  - Aggravation of nonalcoholic steatohepatitis by moderate alcohol consumption is
      associated with decreased SIRT1 activity in rats.
AB  - Chronic alcohol intake decreases adiponectin and sirtuin 1 (SIRT1) expressions,
      both of which have been implicated in various biological processes including
      inflammation, apoptosis and metabolism. We have previously shown that moderate
      consumption of alcohol aggravates liver inflammation and apoptosis in rats with
      pre-existing nonalcoholic steatohepatitis (NASH). This study investigated whether
      moderate alcohol intake alters SIRT1 activity, adiponectin/Adiponectin receptor
      (AdipoR)-related signaling and lipid metabolism in a pre-existing NASH status.
      Sprague-Dawley rats were fed with a high-fat diet (71% energy from fat) for 6
      weeks to induce NASH then subsequently divided into 2 sub-groups: fed either a
      modified high-fat diet (HFD, 55% energy from fat) or a modified high-fat
      alcoholic diet (HFA, 55% energy from fat and 16% energy from ethanol) for an
      additional 4 weeks. We observed in comparison to HFD group, HFA increased hepatic
      nuclear SIRT1 protein but decreased its deacetylase activity. SREBP-1c protein
      expression and FAS mRNA levels were significantly upregulated, while DGAT1/2 and
      CPT-I mRNA levels were downregulated in the livers of HFA compared to HFD.
      Although hepatic AdipoR1 decreased, HFA did not alter AdipoR2 and their
      downstream signaling. There were no significant changes in plasma adiponectin and
      free fatty acids (FFA), as well as adiponectin expression in adipose tissue
      between the two groups. The present study indicates that suppression in SIRT1
      deacetylase activity contributes to alcohol-exacerbated hepatic inflammation and
      apoptosis in rats with pre-existing NASH. In addition, moderate alcohol intake
      did not modulate adiponectin/AdipoR signaling axis in this model. 

PMID- 24570956
TI  - TP53 mutation is associated with a poor outcome for patients with hepatocellular
      carcinoma: evidence from a meta-analysis.
AB  - BACKGROUND: Various studies examined the relationship between p53 mutation with
      the clinical outcome in patients with hepatocellular carcinoma (HCC), but yielded
      conflicting results. METHODS: Electronic databases updated to July 2013 were
      searched to find relevant studies. A meta-analysis was conducted with eligible
      studies which quantitatively evaluated the relationship between p53 mutation and
      survival of patients with HCC. Survival data were aggregated and quantitatively
      analyzed. RESULTS: We performed a meta-analysis of 9 studies that evaluated the
      correlation between p53 mutation and survival in patients with HCC. Combined
      hazard ratios suggested that p53 mutation had an unfavorable impact on overall
      survival (OS) [hazard ratio (HR) =1.46, 95% confidence interval (CI): 1.15-1.76],
      and disease free survival (DFS) (HR =2.57, 95% CI: 1.46-3.68) in patients with
      HCC. The significant heterogeneity (P=0.035) was observed among 8 studies for OS,
      however no significant heterogeneity (P=0.597) was observed among 5 studies for
      DFS. CONCLUSIONS: p53 mutation indicates a poor prognosis for patients with
      hepatocellular carcinoma.

PMID- 24570957
TI  - Should preoperative biliary drainage be routinely performed for obstructive
      jaundice with resectable tumor?
AB  - Obstructive jaundice is a common clinical manifestation of malignant lesions
      adjacent to extrahepatic bile duct, ampulla or pancreatic head. Animal
      experiments and some clinical observations have demonstrated that preoperative
      biliary drainage could improve liver function as well as reduce endotoxemia,
      thereby reducing the incidence of perioperative complications. However, a number
      of randomized, controlled studies have found that preoperative biliary drainage
      failed to improve prognosis or reduce the incidence of perioperative
      complications; in contrast, it might increase the incidence of complications and
      cause extra financial burden on patients. Thus, whether preoperative biliary
      drainage should be performed or not is controversial. Since clinical randomized
      controlled studies are more relevant in clinical setting, we believe that
      preoperative biliary drainage should not be routinely performed for obstructive
      jaundice with resectable tumors. More randomized, controlled, prospective studies
      should be conducted for further exploration. 

PMID- 24570960
TI  - Multiple liver lesions with dormant submandibular gland nodule.

PMID- 24570958
TI  - Cholangiocarcinoma: increasing burden of classifications.
AB  - Cholangiocarcinoma (CCA) is a very heterogeneous cancer from any point of view,
      including epidemiology, risk factors, morphology, pathology, molecular pathology,
      modalities of growth and clinical features. Given this heterogeneity, a uniform
      classification respecting the epidemiologic, pathologic and clinical needs is
      currently lacking. In this manuscript we discussed the different proposed
      classifications of CCA in relation with recent advances in pathophysiology and
      biology of this cancer. 

PMID- 24570959
TI  - Assessment of nodal status for perihilar cholangiocarcinoma location, number, or
      ratio of involved nodes.
AB  - Surgical treatment of perihilar cholangiocarcinoma (PCC) is the treatment of
      choice that can achieve long term results. Unfortunately the presence of lymph
      node metastases is frequent and it is one of the major negative prognostic
      factors in patients submitted to surgery. In literature there are few data about
      the prognostic significance of location, number and ratio of involved nodes.
      Moreover guidelines about the extent of lymph node dissection are not available.
      In this commentary the data of literature about prognostic significance of lymph
      node involvement are described and analysed. 

PMID- 24570962
TI  - China's surgical expert consensus on the diagnosis and treatment of
      cholangiocarcinoma: an interpretation.

PMID- 24570961
TI  - The therapeutic potential of brown adipose tissue.

PMID- 24570963
TI  - Professor William Jarnagin: biliary malignancy.

PMID- 24570964
TI  - Professor Javier C. Lendoire: colorectal liver metastases.

PMID- 24570965
TI  - Engagement vs. isolationism: China's transplant system.

PMID- 24570966
TI  - Network meta-analysis on prophylactic regimens against recurrent hepatitis B
      virus infection after liver transplantation.
AB  - BACKGROUND: Previous meta-analyses of non-randomized studies suggested that the
      hepatitis B immunoglobulin (HBIG) and lamivudine (LAM) combination therapy was
      significantly better than HBIG or LAM alone in preventing hepatitis B virus (HBV)
      recurrence after transplantation. However, substantial evidences supporting the
      superiority of combination therapy are still insufficient. Therefore, we sought
      to conduct a multiple-treatment comparison to integrate current data which was
      based on randomized controlled trials (RCTs). METHODS: We searched electronic
      databases of PubMed, Embase and the Cochrane Library for eligible literatures.
      Pair-wise meta-analyses were to synthesize studies comparing the same pair of
      treatments. Appropriate networks for overall and 1-year recurrence rates were
      established. Bayesian algorithm was used in multiple-treatment comparisons to
      compare relative effects of all included regimens. RESULTS: Four RCTs on
      prophylaxis against HBV recurrence after liver transplantation, involving 162
      participants, were included. HBIG mono-therapy, LAM mono-therapy and HBIG plus
      LAM showed no statistically difference in risk ratios (RRs) in terms of overall
      HBV recurrence rate in network meta-analysis. Nevertheless, HBIG mono-therapy had
      potential advantage compared with combination of HBIG and LAM in 1-year HBV
      recurrence rate [RR 0.00, 95% confidence interval (CI): 0.00 to 0.91] while the
      rest comparisons revealed no significance. The cumulative probabilities of
      treatments associated with the highest recurrence were (overall HBV recurrence
      rate, 1-year HBV recurrence rate): HBIG (18%, 1%), LAM (32%, 42%) and HBIG plus
      LAM (50%, 57%). CONCLUSIONS: This network meta-analysis based on data from RCTs
      showed no significant differences among HBIG mono-therapy, LAM mono-therapy,
      combination of HBIG and LAM in overall HBV recurrence rate after liver
      transplantation. Further well designed and large-scale RCTs are warranted to
      clarify these issues.

PMID- 24570967
TI  - Organ transplantation is getting back its "true" luster in China.
AB  - Although a great success has been made in the field of organ transplantation in
      China, the practice of organ donation from executed prisoners has long been
      rebuked by the international transplant community. The "boycott" attitude of
      western countries has stifled the development of transplant science and medicine
      in China. With the efforts of the Chinese government and transplant community, a
      voluntary organ donation system has been successfully established. The medical
      authorities have committed that the practice of using organs from executed
      prisoners will be abandoned in the near future. It is time for a big hug from the
      international transplant community to its Chinese partner. And it is time for a
      rapid development of organ transplantation in China. 

PMID- 24570968
TI  - New national policy for deceased organ donation in China.

PMID- 24570969
TI  - Responses to comments on "Liver transplantation in mainland China: the overview
      of CLTR 2011 annual scientific report".

PMID- 24570970
TI  - Professor Ronald W. Busuttil: my opinion about the national program for diseased
      organ donation in China.

PMID- 24570971
TI  - Prof. Anita S. Chong: focused research in transplantation tolerance.

PMID- 24570972
TI  - Hangzhou Resolution announcement ceremony.

PMID- 24570973
TI  - OTC Hangzhou Resolution.

PMID- 24570974
TI  - The Transplantation Society embraces the national program for diseased organ
      donation in China: "TTS President Francis L. Delmonico"s China Trip.

PMID- 24570976
TI  - EJOI New Year's wishes.

PMID- 24570975
TI  - Human regulatory T cells kill tumor cells through granzyme-dependent cytotoxicity
      upon retargeting with a bispecific antibody.
AB  - A major mechanism by which human regulatory T cells (T(regs)) have been shown to
      suppress and kill autologous immune cells is through the granzyme-perforin
      pathway. However, it is unknown whether T(regs) also possess the capacity to kill
      tumor cells using similar mechanisms. Bispecific antibodies (bscAbs) have emerged
      as a promising class of therapeutics that activate T cells against tumor antigens
      without the need for classical MHC-restricted TCR recognition. Here, we show that
      a bscAb targeting the tumor-specific mutation of the epidermal growth factor
      receptor, EGFRvIII, redirects human CD4(+)CD25(+)FoxP3(+) T(regs) to kill
      glioblastoma (GBM) cells. This activity was significantly abrogated by inhibitors
      of the granzyme-perforin pathway. Notably, analyses of human primary GBM also
      displayed diffuse infiltration of granzyme-expressing FoxP3(+) T cells. Together,
      these data suggest that despite their known suppressive functions, tumor
      infiltrating T(regs) possess potent cytotoxic mechanisms that can be co-opted for
      efficient tumor cell lysis.

PMID- 24570977
TI  - Letter regarding a case report of severe bleeding after sinus floor elevation
      using the transcrestal approach published in EJOI in 2012.
AB  - A case report of severe bleeding after sinus floor elevation using the
      transcrestal approach was published in EJOI in the third issue of 2012 by Dr
      Simon Storgard Jensen and coworkers1. EJOI has received a letter regarding this
      case report from Dr Federico Mandelli and Dr Tiziano Testori. EJOI has decided to
      publish this letter together with the answers from the authors as well as minor
      comments from the EJOI editors. It is our hope that the letter and the reply will
      provide readers with improved interpretation and understanding of the case report
      presented.

PMID- 24570978
TI  - Response to 'Letter regarding a case report of severe bleeding after sinus floor
      elevation using the transcrestal approach published in EJOI in 2012'.

PMID- 24570979
TI  - Different implant impression techniques for edentulous patients treated with
      CAD/CAM complete-arch prostheses: a randomised controlled trial reporting data at
      3 year post-loading.
AB  - PURPOSE: To compare two different impression techniques for implants in totally
      edentulous patients. MATERIALS AND METHODS: A total of 38 patients had
      impressions taken both using plaster and splinted vinyl polysiloxane (splinted
      VPS). Two casts per patient were generated and allocated as test (plaster) and
      control (splinted-VPS) cast groups according to a randomised cross-over design.
      One of the two casts from each patient was randomly selected as master cast
      according to a parallelgroup design and used to fabricate the definitive
      prosthesis. Outcome measures were implant and prosthetic success rates,
      complications, marginal bone level (MBL) changes, patient satisfaction, chair
      time required to take the impressions, inter-implant discrepancy between the
      casts, sulcus bleeding index (SBI) and plaque score (PS). RESULTS: In total, 76
      impressions were taken in 38 patients. Two plaster impressions failed.
      Furthermore, 38 computer-aided design/computer-assisted manufacturing screw
      retained complete-arch prostheses were fabricated onto the master cast (18 from
      plaster and 20 from splinted-VPS impressions) and the patients were followed up
      for 3 years after loading. No drop-out occurred and no implants or prostheses
      failed, accounting for a cumulative implant and prosthesis survival rate of 100%
      over the 3-year post-loading period. Plaster impressions yielded significantly
      greater patient satisfaction and shorter chair time. The discrepancy between the
      casts was 0.055 +/- 0.067 mm (P = 0.931). Mixed model analysis revealed a
      significant main effect from both the implant number and the inter-implant
      distance, while no difference was found with regard to implant angulation. Five
      chip-off fractures of the porcelain veneer occurred in 5 of the 38 patients (3 in
      restorations fabricated onto the plaster cast group and 2 in the splinted-VPS
      cast group) with no effect from the type of impression on the prosthetic success
      rate (P = 0.331). However, all of the patients were functionally and
      aesthetically satisfied with their prostheses. Furthermore, mean MBL, SBI and PS
      showed no significant differences (P > 0.05) between the groups. CONCLUSIONS: The
      clinical outcome of plaster impressions for completely edentulous patients was
      found to be the same as that for splinted-VPS impressions. The intraoral pre-scan
      resin framework try-in can be avoided. Plaster impressions may be less time
      consuming and thus more comfortable for the patient, but sometimes may have to be
      repeated due to fractures. CONFLICT-OF-INTEREST STATEMENT: All materials used in
      this study were purchased by the authors and there were no commercial or
      institutional interests.

PMID- 24570980
TI  - Posterior atrophic jaws rehabilitated with prostheses supported by 5 x 5 mm
      implants with a novel nanostructured calcium-incorporated titanium surface or by
      longer implants in augmented bone. One-year results from a randomised controlled
      trial.
AB  - PURPOSE: To evaluate whether 5 * 5 mm dental implants with a novel nanostructured
      calciumincorporated titanium surface could be an alternative to implants at least
      10 mm long placed in bone augmented with bone substitutes in posterior atrophic
      jaws. MATERIALS AND METHODS: A total of 40 patients with atrophic posterior
      (premolar and molar areas) mandibles having 5 to 7 mm of bone height above the
      mandibular canal and 40 patients with atrophic maxillae having 4 to 6 mm below
      the maxillary sinus, were randomised according to a parallel group design to
      receive one to three 5 mm implants or one to three at least 10 mm-long implants
      in augmented bone at two centres. All implants had a diameter of 5 mm. Mandibles
      were vertically augmented with interpositional bovine bone blocks and resorbable
      barriers. Implants were placed after 4 months. Maxillary sinuses were augmented
      with particulated porcine bone via a lateral window covered with resorbable
      barriers and implants were placed simultaneously. All implants were submerged and
      loaded after 4 months with provisional prostheses. Four months later, definitive
      screw-retained or provisionally cemented metal-ceramic or zirconia prostheses
      were delivered. Patients were followed up to 1 year post-loading and the outcome
      measures were prosthesis and implant failures, any complications and peri-implant
      marginal bone level changes. RESULTS: One maxillary grafted patient dropped out
      before the 1-year evaluation. In mandibles, 1 grafted patient did not want to go
      ahead with the treatment because of multiple complications and graft failure, and
      another grafted patient did not receive his prostheses due the loss of 2
      implants. In maxillae, one 5 * 5 mm implant failed with its provisional crown 3
      months post-loading. There were no statistically significant differences in
      prostheses and implant failures. Significantly more complications occurred at
      both mandibular and maxillary grafted sites: 17 augmented patients were affected
      by complications versus 8 patients treated with short implants in the mandible (P
      = 0.0079; difference in proportion = -0.45; 95% CI -0.67 to -0.15), and 5 sinus
      lift patients versus none treated with maxillary short implants (P = 0.047;
      difference in proportion = -0.25; 95% CI -0.44 to -0.06). Patients with
      mandibular short implants lost on average 0.94 mm of peri-implant bone at 1 year
      and patients with 10 mm or longer mandibular implants lost 1.03 mm. Patients with
      maxillary short implants lost on average 0.87 mm of peri-implant bone at 1 year
      and patients with 10 mm or longer maxillary implants lost 1.15 mm. There were no
      statistically significant differences in bone level changes up to 1 year between
      short and longer implants in maxillae (mean difference -0.28 mm, 95% CI -0.56 to
      0.01, P = 0.051) and in mandibles (mean difference -0.09 mm, 95% CI -0.26 to
      0.08, P = 0.295). CONCLUSIONS: One year after loading, 5 * 5 mm implants achieved
      similar results compared to longer implants placed in augmented bone. Short
      implants might be a preferable choice to bone augmentation especially in
      posterior mandibles since the treatment is faster, cheaper and associated with
      less morbidity, however 5 to 10 years of post-loading data are necessary before
      making reliable recommendations. CONFLICT-OF-INTEREST STATEMENT: MegaGen
      partially supported this trial and donated implants and prosthetic components
      used in this study, whereas Tecnoss donated the biomaterials. The data belonged
      to the authors and by no means did the manufacturers interfere with the conduct
      of the trial or the publication of its results.

PMID- 24570981
TI  - Posterior atrophic jaws rehabilitated with prostheses supported by 6 mm long 4 mm
      wide implants or by longer implants in augmented bone. One-year post-loading
      results from a pilot randomised controlled trial.
AB  - PURPOSE: To evaluate whether 6 mm long by 4 mm wide dental implants could be an
      alternative to implants at least 10 mm long placed in bone augmented with bone
      substitutes in posterior atrophic jaws. MATERIALS AND METHODS: A total of 20
      patients with bilateral atrophic mandibles and 20 patients with bilateral
      atrophic maxillae, having 5 to 7 mm of bone height above the mandibular canal or
      below the maxillary sinus, had each side of the jaws randomly allocated according
      to a split-mouth design. They were allocated to receive one to three 6 mm long
      and 4 mm wide implants, or implants at least 10 mm long in augmented bone by two
      different surgeons in different centres. Mandibles were vertically augmented with
      interpositional equine bone blocks and resorbable barriers, and implants were
      placed 3 months later. Maxillary sinuses were augmented with particulated porcine
      bone via a lateral window and implants were placed simultaneously. All implants
      were submerged and loaded, after 4 months, with provisional prostheses. Four
      months later, definitive metal-ceramic prostheses were delivered. Outcome
      measures were prosthesis and implant failures, any complication and radiographic
      peri-implant marginal bone level changes. RESULTS: One patient treated in the
      mandible dropped out before the 1-year post-loading follow-up. All maxillary
      implants and prostheses were successful, whereas 2 mandibular prostheses could
      not be placed on implants at least 10 mm long due to graft failures; one was
      associated with the loss of 3 implants because of infection. There were no
      statistically significant differences in implant and prosthesis failures, though
      significantly more complications occurred at grafted sites in mandibles (P =
      0.0078), but not in maxillae (P = 0.1250). In total, 14 complications occurred in
      12 patients at augmented sites versus none at 6 mm-long implants. All failures
      and complications occurred before loading. Patients with mandibular 6 mm-long
      implants lost an average of 1.05 mm of peri-implant bone at 1 year and patients
      with mandibular implants at least 10 mm long lost 1.07 mm. These differences were
      statistically significant (P < 0.001). Patients with maxillary 6 mm-long implants
      lost an average of 1.02 mm of peri-implant bone at 1 year and patients with
      maxillary implants at least 10 mm long lost 1.09 mm. These differences were
      statistically significant (P < 0.001). There were no statistically significant
      differences in bone level changes up to 1 year between 6 mm and at least 10 mm
      long implants in both jaws (mandibles n = 18, mean difference -0.02 mm, 95% CI 
      0.16 to 0.12, P = 0.7384; maxillae n = 20, mean difference -0.07 mm, 95% CI -0.18
      to 0.05, P = 0.2547). CONCLUSIONS: Short-term data (1 year after loading)
      indicate that 6 mm-long implants with a conventional diameter of 4 mm achieved
      similar if not better results than longer implants placed in augmented bone.
      Short implants might be a preferable choice to bone augmentation, especially in
      posterior mandibles since the treatment is faster, cheaper and associated with
      less morbidity. However, data obtained 5 to 10 years after loading are necessary
      before making reliable recommendations. CONFLICT OF INTEREST STATEMENT: Tecnoss
      and Southern Implants partially supported this trial and donated biomaterials,
      implants and prosthetic components used in this study. However, the data belonged
      to the authors and by no means did the manufacturers interfere with the conduct
      of the trial or the publication of its results.

PMID- 24570982
TI  - The bony lid approach in pre-implant and implant surgery: a prospective study.
AB  - PURPOSE: The aim of this prospective study is to evaluate the outcome of the bony
      lid approach in pre-implant and implant surgery. MATERIALS AND METHODS: A total
      of 200 consecutive patients were treated between 2003 and 2008 with the bony lid
      technique in a prospective study and followed up for at least 4 years. The bony
      lid approach consisted in cutting and luxating a bony lid using a microsaw, which
      was then repositioned at the end of the surgery to avoid large bone defects in
      the case of osteotomies. In 146 cases the bony lid approach was used for implant
      explantation, in 29 cases for removal of fractured roots or foreign bodies from
      the implant site, in 14 cases for removal of impacted teeth from the implant
      site, in 4 patients in combination with nerve decompression/nerve lateralisation,
      and in 7 cases for removal of implants from the sinus. In 76 patients, the bony
      lid technique was performed simultaneously with the implant insertion or bone
      grafting procedure. In the remaining 124 cases, the bone grafting
      procedure/implant insertion was performed 3 months postoperatively. Outcome
      measures were success of the procedure, complications and stability of the bone
      volume of the alveolar crest. RESULTS: All of the bony lid procedures obtained
      the desired aim and healed without any complication. The re-entry showed, in most
      cases (98.5%), a well integrated vestibular bone wall with volume stability. The
      average width of the alveolar crest after the reimplantation of the bony lid was
      7.6 +/- 0.8 mm in 124 patients, where the bony lid was reimplanted without
      simultaneous implantation/augmentation. At the re-entry 3 months later, an
      average width of 7.1 +/- 1.2 mm was observed. In the 76 patients where the bony
      lid was reimplanted simultaneously with the implant insertion or with the bone
      grafting procedure, normal healing without any infection was observed. Only 3
      cases demonstrated important volume changes, all in the 2-stage group. In all
      patients, it was possible to continue the treatment as planned. CONCLUSION: The
      results of the present study showed good outcomes for the bony lid approach.
      CONFLICT-OF-INTEREST STATEMENT: This study was completely self-supported and no
      contribution from any commercial party was received, even in the form of free
      materials.

PMID- 24570983
TI  - Patient satisfaction and aesthetic outcome of implant-supported single-tooth
      replacements performed by dental students: a retrospective evaluation 8 to 12
      years after treatment.
AB  - PURPOSE: To assess patient satisfaction and aesthetic treatment outcome of
      implant-supported singletooth replacements performed by dental students as part
      of their undergraduate curriculum 8 to 12 years after treatment. MATERIALS AND
      METHODS: A total of 51 patients were consecutively treated by dental students
      with 55 implant-supported single-tooth replacements within the incisor, canine
      and premolar regions. The surgical and prosthetic treatment was performed by the
      dental students under the supervision of dentists and oral and maxillofacial
      surgeons, all with specific knowledge about oral implantology. The outcome
      measures were patient subjective evaluation of peri-implant soft tissues, implant
      crown, implant function and total implant treatment using a Visual Analogue Scale
      (VAS). The professional evaluation included the peri-implant soft tissues,
      implant crown and total implant treatment (combined scores, PES/WES) using the
      Pink Esthetic Score (PES) and the White Esthetic Score (WES), as well as the
      level of incisor edge/occlusal surface in relation to neighbouring teeth.
      RESULTS: A total of 42 patients with 46 implants were available for evaluation 8
      to 12 years after treatment. The patients were in general satisfied with the
      treatment outcome and few patients had low VAS scores. Most implants were
      characterised by single scores of 1 or 2 resulting in a mean PES score of 8.3
      (maximum 14), a mean WES score of 6.3 (maximum 10) and a mean PES/WES score of
      14.6 (maximum 24). However, 33% of the implants were characterised by recession
      (>1 mm) of the facial soft-tissue margin. Correlation analyses involving the
      subjective parameters indicated that the evaluation of the total implant
      treatment was mainly influenced by the appearance of the implant crown and to a
      lesser extent by the peri-implant mucosa. There were no significant correlations
      between the subjective and professional evaluation. Both the subjective and
      professional evaluation revealed implants in infraposition. This was registered
      in 7% and 17% of the implants, respectively. CONCLUSIONS: The patient
      satisfaction and aesthetic outcome 8 to 12 years after treatment with implant
      supported single-tooth replacements performed by dental students as part of their
      clinical undergraduate dental curriculum were characterised by high patient
      satisfaction and an acceptable aesthetic treatment outcome. Therefore, it seems
      acceptable to include implant therapy of straightforward cases in the clinical
      undergraduate curriculum, provided there is substantial supervision by trained
      clinicians. CONFLICT-OF-INTEREST STATEMENT: The study was partially supported by
      Nobel Biocare, Denmark. There was no conflict of interest.

PMID- 24570984
TI  - Parachuting in the evidence-based dentistry minefield.

PMID- 24570985
TI  - Regenerative periodontal therapy.
AB  - The goal of regenerative periodontal therapy is to completely restore the tooth's
      supporting apparatus that has been lost due to inflammatory periodontal disease
      or injury. It is characterized by formation of new cementum with inserting
      collagen fibers, new periodontal ligament, and new alveolar bone. Indeed
      conventional, nonsurgical, and surgical periodontal therapy usually result in
      clinical improvements evidenced by probing depth reduction and clinical
      attachment gain, but the healing occurs predominantly through formation of a long
      junctional epithelium and no or only unpredictable periodontal regeneration.
      Therefore, there is an ongoing search for new materials and improved surgical
      techniques, with the aim of predictably promoting periodontal wound
      healing/regeneration and improving the clinical outcome. This article attempts to
      provide the clinician with an overview of the most important biologic events
      involved in periodontal wound healing/ regeneration and on the criteria on how to
      select the appropriate regenerative material and surgical technique in order to
      optimize the clinical outcomes. 

PMID- 24570986
TI  - Short-term effects of nonsurgical periodontal treatment with and without use of
      diode laser (980 nm) on serum levels of reactive oxygen metabolites and clinical
      periodontal parameters in patients with chronic periodontitis: a randomized
      controlled trial.
AB  - OBJECTIVE: The aim of this study was to compare the clinical efficiency of a
      diode laser as an adjunct to scaling and root planing (SRP) in the treatment of
      chronic periodontitis patients, and also to evaluate the changes in the clinical
      parameters such as clinical attachment level in teeth with periodontal pockets
      and blood reactive oxygen metabolites. METHOD AND MATERIALS: A total of thirty
      patients (mean age 38.2 years) with chronic periodontitis were selected for this
      study. The patients were randomly assigned into two groups of 15 patients each,
      as the control group and test group. The control group received only conventional
      SRP and the test group received conventional SRP and diode laser (GaAlAs)
      assisted pocket debridement. The clinical parameters (Plaque Index, bleeding on
      probing, probing pocket depth, and clinical attachment level) were recorded at
      baseline and day 60, and the serum levels of reactive oxygen metabolites were
      estimated at baseline, day 30, and day 60 for both the groups. RESULTS: When the
      groups were compared, there was statistically significant improvement in Plaque
      Index score, decrease in bleeding on probing and probing pocket depth, and gain
      in clinical attachment level (P < .001) in both the groups from baseline to day
      60. There was significant reduction in reactive oxygen metabolites in both the
      groups from baseline to day 30 and day 60 (P < .001). However no statistically
      significant changes were present between the treatment groups from baseline to
      day 60 in terms of clinical parameters and blood reactive oxygen metabolites.
      CONCLUSION: From the results observed in this study it can be concluded that use
      of diode laser as an adjunct to SRP did not provide any significant difference
      compared to use of SRP alone in terms of clinical parameters and reactive oxygen
      metabolites.

PMID- 24570987
TI  - Negotiating the severely resorbed extraction site: a clinical case report with
      histologic sample.
AB  - The treatment of an infected socket with a severe facial dehiscence/ fenestration
      defect presents a therapeutic dilemma to the dental team. Both implant-supported
      restoration and fixed partial denture are viable options to restore function and
      occlusion, each with its benefits and disadvantages. In the present case report,
      a multi-stage regenerative approach was selected to enable implant-supported
      single crown. The first phase of the treatment after extraction of the maxillary
      central incisor was the stabilization of the blood clot with a collagen plug. Six
      weeks later, the surgical site was re-entered and the socket was grafted with
      biphasic calcium sulfate (BCS). Six months later, a dental implant was placed and
      a core biopsy taken. However, the central portion of the facial defect
      demonstrated only partial regeneration resulting in exposure of six implant
      threads. Freeze-dried bone allograft (FDBA) and a collagen membrane were utilized
      to augment the ridge and cover the exposed threads. The histology of the bone
      core showed a complete resorption of the grafted material with the presence of
      new woven bone throughout the specimen. Clinically, complete defect regeneration
      and augmentation of the alveolar ridge were attained after 4 months. Thus, the
      clinician should consider the pros and cons of this regenerative approach along
      with other more conservative treatment alternatives when dealing with similar
      cases. 

PMID- 24570988
TI  - Evaluation of an air-abrasive device with amino acid glycine-powder during
      surgical treatment of peri-implantitis.
AB  - OBJECTIVE: The aim of this retrospective study was to analyze collected data
      concerning the effect of an air-abrasive device (Perio-Flow(r)) during surgical
      treatment of peri-implantitis without addition of any antimicrobials. METHOD AND
      MATERIALS: Data reports from 22 implants with peri-implantitis surgically treated
      using either an air-abrasive device (Perio- Flow) (test group), or plastic
      curettes and cotton pellets impregnated with saline (control group) were analyzed
      for the present study. Clinical and radiographic parameters plaque index (PI),
      gingival index (GI), probing pocket depth (PPD), and bone loss (BL) were
      previously assessed at baseline, 6 months, and 12 months after treatment. A
      repeated measures ANOVA test was used for each clinical and radiographic
      parameter (PI, GI, PPD, and BL). The implant and the patient were considered
      separately as the statistical unit. RESULTS: Regarding betweengroup comparisons,
      PI scores remained low during the entire study period (at implant and patient
      levels). At the end of the study, GI and PPD reductions were statistically higher
      (P < .05) in the Perio-Flow group (implant level), and no differences were
      observed between the two groups at patient level (P > .05) (repeated measures
      ANOVA test). It was also noted that BL analyses (implant and patient levels)
      revealed no differences between baseline and 12 months in both groups.
      Nevertheless, only 8% from each treatment group were considered stabilized after
      12 months. CONCLUSION: Within the limitations of the present study, both groups
      (Perio-Flow and its control group) revealed a significant reduction of the
      clinical parameters. Moreover, the air-abrasive device group yielded better
      improvements regarding GI and PPD when the implant was considered as the
      statistical unit. However, if the stabilization of the disease was the final
      objective, these two treatments failed in resolving its activity. A longer follow
      up and a larger number of patients would be needed to confirm these results and
      the benefit of adding this air-abrasive method of decontamination to the surgical
      procedure.

PMID- 24570989
TI  - Is a grooved collar implant design superior to a machined design regarding bone
      level alteration? An observational pilot study.
AB  - OBJECTIVE: This retrospective observational pilot study examined differences in
      peri-implant bone level changes (DeltaIBL) between two similar implant types
      differing only in the surface texture of the neck. The hypothesis tested was that
      DeltaIBL would be greater with machined-neck implants than with groovedneck
      implants. METHOD AND MATERIALS: 40 patients were enrolled; n = 20 implants with
      machined (group 1) and n = 20 implants with a rough, grooved neck (group 2), all
      placed in the posterior mandible. Radiographs were obtained after loading (at 3
      to 9 months) and at 12 to 18 months after implant insertion. Case number
      calculation with respect to DeltaIBL was conducted. Groups were compared using a
      Brunner-Langer model, the Mann-Whitney test, the Wilcoxon signed rank test, and
      linear model analysis. RESULTS: After the 12- to 18-month observation period,
      mean DeltaIBL was -1.11 +/- 0.92 mm in group 1 and -1.25 +/- 1.23 mm in group 2.
      DeltaIBL depended significantly on time (P < .001), but not on group. In both
      groups, mean marginal DeltaIBL was significantly less than -1.5 mm. Only
      insertion depth had a significant influence on the amount of periimplant bone
      loss (P = .013). Case number estimate testing for a difference between group 1
      and 2 with a power of 90% revealed a sample size per group of 1,032 subjects.
      CONCLUSION: DeltaIBL values indicated that both implant designs fulfilled implant
      success criteria, and the modification of implant neck texture had no significant
      influence on DeltaIBL.

PMID- 24570990
TI  - Diagnosis and interdisciplinary treatment of a botryoid odontogenic cyst in the
      posterior mandible: report of a case.
AB  - Botryoid odontogenic cysts (BOC) are considered to be rare polycystic variants of
      lateral periodontal cysts characterized by a multilocular growth pattern. The
      most frequent location of BOC is the mandible, predominantly the premolar-canine
      area, followed by the anterior region of the maxilla. The cyst shows a slight
      female predilection. This case report of a BOC demonstrates a treatment with
      initial fenestration and decompression of the cyst in order to prevent damage to
      adjacent structures such as the inferior alveolar nerve. The present case report
      emphasizes the importance of accurate clinical, radiographic, and histologic
      diagnostic procedures of unspecific radiolucent lesions in the jaws to establish
      a firm diagnosis and avoid inappropriate treatment strategies. 

PMID- 24570991
TI  - Management of third molar removal with doses of native plasma-derived factor IX
      (Octanine) and local measures in a female patient with severe hemophilia B: a
      case report.
AB  - Patients with hemophilia are at high risk of bleeding following oral surgery. As
      an X-linked recessive chromosomal bleeding disorder it is very rare in female
      patients. This is the first described case of management of third molar removal
      in a female patient suffering from severe hemophilia B. Excellent hemostasis was
      achieved by following a protocol using defined pre- and postoperative doses of
      factor IX and local hemostatic measures of collagen fleece, fibrin glue, primary
      suture, and tranexamic acid solution. Following defined protocols is essential in
      the management of oral surgery in patients with hemophilia and helps to prevent
      postoperative hemorrhages. 

PMID- 24570992
TI  - Intraoral hyperplastic Fordyce granule with destruction of bone: a case
      presentation.
AB  - Fordyce granules of the oral mucosa are often discovered during routine dental
      examinations. They are considered anatomic variations and are typically seen on
      the labial and buccal mucosa in adults. The present case report describes for the
      first time in the literature an atypical location of an enlarged Fordyce granule
      with local bone destruction. The diagnostic process, surgical treatment, and
      follow-up are presented and discussed. 

PMID- 24570993
TI  - A possible association of idiopathic osteosclerosis with excessive occlusal
      forces.
AB  - OBJECTIVES: The aim of the study was to determine the relationship between
      idiopathic osteosclerotic lesions and occlusal forces using the T-Scan II
      computerized occlusal analysis device, and to test the sensitivity of the system
      in occlusal analysis. METHOD AND MATERIALS: The study was conducted with 21
      volunteers with idiopathic osteosclerosis (IO; 14 women, 7 men) aged between 17
      and 62 years (mean 29.95). For every patient, seven or eight recordings were made
      with the T-Scan II occlusal analysis device in maximum intercuspation, and the
      last two (excluding any with technical problems) were chosen for evaluation. For
      each lesion-related area, the distribution of high occlusal forces from two
      different movies was analyzed. RESULTS: In 18 patients (85.71%), lesions were
      observed in an area of high occlusal force, and in 13 patients (61.9%), the
      lesions were located at the first area subjected to high occlusal forces. The
      percentage distribution of high forces at a lesion related area ranged from 0% to
      88%. On average, the high forces at an osteosclerotic lesion area accounted for
      20% of the maximum total force. No statistical differences were observed between
      the measurements of the two selected recordings (P > .05). CONCLUSION: The
      findings of this study suggest a possible relationship between IO and occlusal
      forces and primary contacts. T-Scan II was found to be a successful diagnostic
      device for detecting primary contacts and excessive occlusal forces.

PMID- 24570995
TI  - Oral hygiene instructions provided by dental hygienists: results from a self
      report cohort study and a suggested protocol for oral hygiene education.
AB  - OBJECTIVE: To investigate the extent to which dental hygienists target their
      efforts toward patients' oral hygiene instruction. METHOD AND MATERIALS: A
      population of 179 dental hygienists who attended an annual meeting were given a
      structured anonymous questionnaire to assess information regarding their habits
      of instructing patients about oral hygiene measures. RESULTS: The dental
      hygienists were females aged 21 to 68 years (mean age 39.05 +/- 18.18); 49.7%
      worked in private practice, 21.7% in public practice, and 28.57% in both.
      Overall, 70.9% reported that they provided oral hygiene instruction to all their
      patients; 28.5% to most of their patients; and 0.6% reported that they never
      provided oral hygiene instruction. Among the participants, 54.5% reported giving
      instruction at every treatment, 41% at every periodic treatment, and 4.5% only on
      first meeting. The reasons for not instructing their patients included: lack of
      time (21.7%), the patients know how to brush (61.5%), and the patient appears
      uninterested (23.6%). Most of the participants (77.7%) reported giving the same
      hygiene instructions for patients at high and low risk for caries and/or
      periodontal disease. CONCLUSION: Participants did not use enough demonstration
      methods in order to improve their patients' performance. Dental hygienists should
      pay more attention to instruction and education regarding oral hygiene preventive
      measures. Dental practitioners employing hygienists should encourage oral hygiene
      instruction programs in their clinics. Those programs should include repetitious
      demonstrations and reinforcement in order to improve overall outcome and
      prevention of future disease.

PMID- 24570996
TI  - Geriatric dentistry: a changing paradigm.

PMID- 24570994
TI  - Reliability of multiple-degree incisal/occlusal tooth wear assessment on dental
      casts: findings from a fiveexaminer investigation and related clinical
      implications.
AB  - OBJECTIVE: The aim was to answer the clinical research question: is
      incisal/occlusal tooth wear assessment on dental casts performed by five
      professionals with expertise in different fields of dentistry reliable? METHOD
      AND MATERIALS: Five examiners with different fields of expertise in the dental
      profession assessed tooth wear on dental casts of 45 subjects, based on a six
      degree rating of incisal/occlusal wear. After a calibration meeting, the
      examiners evaluated the casts individually and various issues concerning
      interexaminer agreement and reliability were assessed. RESULTS: A total of 872
      teeth were evaluated. The five examiners agreed only for the rating of 6.6% of
      the teeth. The teeth with the highest percentage of agreement were the premolars.
      Pairwise comparison of the assessments of the examiners #1 (bruxism expert), #2
      (orthodontist), #3 (temporomandibular disorders [TMD] and occlusion expert), #4
      (dental nurse) showed fair to moderate agreement, with kappa-values ranging from
      0.306 to 0.577, whilst the examiner #5 (lab technician) achieved low
      interexaminer reliability values with all the other four examiners. CONCLUSION:
      The interexaminer reliability of tooth wear assessment on dental casts performed
      by five professionals with expertise in different fields of dentistry is highly
      variable. General practitioners should keep in mind that consensus decisions by
      the examiners and assessment by raters belonging to the same dental discipline
      are recommended strategies to increase the reliability of tooth wear evaluation
      in the clinical setting. CLINICAL SIGNIFICANCE: This investigation adds to the
      literature suggesting that, in a clinical setting, a single examiner's assessment
      of tooth wear on dental casts does not have optimal reliability and that it may
      be source of internal validity problems in the research setting.

PMID- 24570997
TI  - All-ceramic resin-bonded fixed dental prostheses: treatment planning, clinical
      procedures, and outcome.
AB  - Single-retainer resin-bonded fixed dental prostheses (RBFDPs) present a minimally
      invasive treatment option as an alternative to implant-retained restorations in
      the esthetic zone. Advantages such as applicability to juvenile patients who do
      not come into consideration for implant therapy, and highly predictable and
      esthetic results make them a valuable treatment modality. This article outlines
      the treatment procedures with an all-ceramic RBFDP and reviews the existing data
      on the clinical outcome of this prosthetic therapy. The materials used for
      fabrication and insertion of the RBFDPs as well as the current scientific data
      are discussed. 

PMID- 24570998
TI  - Nativity status and oral cancer survival in the United States: implications for
      dental clinical practice.
AB  - OBJECTIVE: Nativity status is a major determinant of health and healthcare access
      in the United States. This study compared oral squamous cell carcinoma (OSCC)
      survival between US-born and foreign-born patients. METHOD AND MATERIALS: Data
      were obtained from the 1988-2008 Surveillance, Epidemiology and End Results
      database. A Cox proportional hazards multivariate model was used to assess the
      eff ect of birthplace on OSCC survival, adjusting for other sociodemographic and
      clinical covariates. RESULTS: US-born patients had a higher median survival time
      (19.3 years; 95% confidence interval [CI]: 18.6-19.7) compared to foreign-born
      patients (10.7 years; 95% CI: 10.1-11.3). After adjusting for other factors,
      being born in the US conferred a modest protective eff ect from OSCC mortality
      (hazard ratio [HR] = 0.93, 95% CI: 0.87- 0.99). Other factors that conferred
      better survival included involvement of paired structures (HR = 0.65; 95% CI:
      0.58- 0.74), lip involvement rather than tongue lesions (HR = 0.76; 95% CI: 0.71
      0.82), and receipt of either surgery (HR = 0.89; 95% CI: 0.84-0.94) or radiation
      therapy (HR = 0.92; 95% CI: 0.87-0.97). CONCLUSION: US-born patients had
      significantly better OSCC survival compared to their foreign-born counterparts.
      This underscores the need for enhanced and sustained efforts to improve access to
      healthcare among immigrant populations. In addition, oral health professionals
      such as general dentists, oral pathologists, and oral surgeons providing care to
      immigrant patients should ensure that reasonable efforts are made to communicate
      effectively with patients with language barriers, especially in high-stake
      conditions such as cancer. This may help increase such patients' awareness of
      treatment provided and the critical issues regarding cancer care, resulting in
      enhanced treatment outcome.

PMID- 24570999
TI  - Identification of pathogenic fungi with an optoelectronic nose.
AB  - Human fungal infections have gained recent notoriety following contamination of
      pharmaceuticals in the compounding process. Such invasive infections are a more
      serious global problem, especially for immunocompromised patients. While
      superficial fungal infections are common and generally curable, invasive fungal
      infections are often life-threatening and much harder to diagnose and treat.
      Despite the increasing awareness of the situation's severity, currently available
      fungal diagnostic methods cannot always meet diagnostic needs, especially for
      invasive fungal infections. Volatile organic compounds produced by fungi provide
      an alternative diagnostic approach for identification of fungal strains. We
      report here an optoelectronic nose based on a disposable colorimetric sensor
      array capable of rapid differentiation and identification of pathogenic fungi
      based on their metabolic profiles of emitted volatiles. The sensor arrays were
      tested with 12 human pathogenic fungal strains grown on standard agar medium.
      Array responses were monitored with an ordinary flatbed scanner. All fungal
      strains gave unique composite responses within 3 hours and were correctly
      clustered using hierarchical cluster analysis. A standard jackknifed linear
      discriminant analysis gave a classification accuracy of 94% for 155 trials.
      Tensor discriminant analysis, which takes better advantage of the high
      dimensionality of the sensor array data, gave a classification accuracy of 98.1%.
      The sensor array is also able to observe metabolic changes in growth patterns
      upon the addition of fungicides, and this provides a facile screening tool for
      determining fungicide efficacy for various fungal strains in real time. 

PMID- 24571000
TI  - Ion dynamics in a trapped ion mobility spectrometer.
AB  - In the present paper, theoretical simulations and experimental observations are
      used to describe the ion dynamics in a trapped ion mobility spectrometer. In
      particular, the ion motion, ion transmission and mobility separation are
      discussed as a function of the bath gas velocity, radial confinement, analysis
      time and speed. Mobility analysis and calibration procedure are reported for the
      case of sphere-like molecules for positive and negative ion modes. Results showed
      that a maximal mobility resolution can be achieved by optimizing the gas
      velocity, radial confinement (RF amplitude) and ramp speed (voltage range and
      ramp time). The mobility resolution scales with the electric field and gas
      velocity and R = 100-250 can be routinely obtained at room temperature. 

PMID- 24571001
TI  - In situ molecular imaging of a hydrated biofilm in a microfluidic reactor by ToF
      SIMS.
AB  - A novel microfluidic reactor for biofilm growth and in situ characterization
      using time-of-flight secondary ion mass spectrometry (ToF-SIMS) was constructed
      to enable two-dimensional chemical imaging of hydrated biofilms. We demonstrate
      the detection of characteristic fatty acid fragments from microfluidic reactor
      grown biofilms and illustrate advantages of hydrated-state ToF-SIMS imaging. 

PMID- 24571003
TI  - Editors' introduction to Hearing Research special issue: music: a window into the
      hearing brain.

PMID- 24571002
TI  - Advance medical directives: a proposed new approach and terminology from an
      Islamic perspective.
AB  - Advance directives are specific competent consumers' wishes about future medical
      plans in the event that they become incompetent. Awareness of a patient's
      autonomy particularly, in relation to their right to refuse or withdraw
      treatment, a right for the patient to die from natural causes and interest in end
      of life issues were among the main reasons for developing and legalizing advance
      medical directives in developed countries. However, in many circumstances
      cultural and religious aspects are among many factors that can hamper
      implementation of advance directives. Islam and Muslims in general have a good
      understanding of death and dying. Islam allows the withholding or withdrawal of
      treatments in some cases where the intervention is considered futile. However,
      there is lack of literature and debate about such issues from an Islamic point of
      view. This article provides the Islamic perspective with regards to advance
      medical directive with the hope that it will generate more thoughts and evoke
      further discussion on this important topic.

PMID- 24571004
TI  - The instrumental Nathaniel Bishop Harman (1869-1945).

PMID- 24571006
TI  - Princeton University can import vaccine to combat meningitis outbreak.

PMID- 24571005
TI  - Population-based referrals for adjuvant radiotherapy after radical prostatectomy
      in men with prostate cancer: impact of randomized trials.
AB  - INTRODUCTION: To examine the impact of published randomized controlled trial
      (RCT) data on referrals for adjuvant radiotherapy (RT) in patients who had high
      risk pathologic features after radical prostatectomy (RP). METHODS: In this
      population-based, retrospective Canadian study, all patients who received a
      diagnosis of prostate adenocarcinoma and underwent RP from 2003-2008 were
      identified through the Manitoba Cancer Registry. Manual review of pathology
      reports was performed, and patients who had high-risk pathologic features of
      extracapsular extension, seminal vesicle invasion, or positive surgical margins
      were included. Referrals for adjuvant RT were examined before and after
      publication of RCT data to determine their influence on practice. Multivariable
      logistic regression was used to identify factors related to referral. RESULTS: Of
      the 1080 identified patients, 546 (50.6%) had >= 1 high-risk pathologic feature.
      Only 78 (14.3%) of the 546 patients were referred for adjuvant RT within 6 months
      of RP. Year of diagnosis, in relation to the publication of the RCT, was not
      significantly associated with referral (P =.60). Higher pT stage (P < .0001),
      Gleason score (P =.035), and increased distance from cancer center (P =.004) were
      associated with referral. CONCLUSION: In patients who had high-risk pathologic
      features after RP, referral rates for adjuvant RT were low and did not increase
      after presentation of RCT. Men who had higher pT stage, Gleason score, and rural
      residence were more likely to be referred.

PMID- 24571007
TI  - FDA drug safety communication: FDA requests label changes and single-use
      packaging for some over-the-counter topical antiseptic products to decrease risk
      of infection.

PMID- 24571008
TI  - Primary amebic meningoencephalitis associated with ritual nasal rinsing-St
      Thomas, US Virgin Islands, 2012.

PMID- 24571009
TI  - Encephalitis and bocavirus?

PMID- 24571010
TI  - HIV controllers: not in total control.

PMID- 24571011
TI  - [The German Cancer Society].

PMID- 24571012
TI  - Reflections: neurology and the humanities. Odd harvest.

PMID- 24571014
TI  - [The Professional Association of Gastroenterologists Germany e. V. informed].

PMID- 24571013
TI  - Periprostatic adipose tissue from obese prostate cancer patients promotes tumor
      and endothelial cell proliferation: a functional and MR imaging pilot study.
AB  - BACKGROUND: Obesity, particularly visceral adiposity, confers a worse prognosis
      for prostate cancer (PCa) patients, and increasing periprostatic adipose (PPA)
      tissue thickness or density is positively associated with more aggressive
      disease. However, the cellular mechanism of this activity remains unclear.
      Therefore, in this pilot study, we assessed the functional activity of PPA tissue
      secretions and established a biochemical profile of PPA as compared to
      subcutaneous adipose (SQA) tissues from lean, overweight and obese PCa patients.
      METHODS: Adipose tissues were collected from PCa patients undergoing surgical
      prostate removal. Tissues were analyzed by histologic and magnetic resonance (MR)
      techniques. Explant tissue culture secretions were used in proliferation assays
      on PCa and endothelial cells. RESULTS: PPA secretions obtained from obese
      patients were significantly more pro-proliferative in both PCa and endothelial
      cells as compared to PPA obtained from lean or overweight men and SQA tissues.
      Consistent with this, PPA microvessel density was increased, and the T2
      relaxation time was decreased, compared to SQA tissues, and we observed a modest,
      inverse correlation between the T2 and tumor stage. Moreover, the ratio of
      unsaturated to saturated fatty acids, obtained using MR spectroscopy, showed a
      modest, inverse correlation with Gleason score. CONCLUSIONS: These pilot data
      show that PPA stimulates PCa cell proliferation and angiogenesis and that obesity
      intensifies this activity, thus generating a mechanistic hypothesis to explain
      the worse prognosis observed in obese PCa patients. Our pilot study also shows
      that MR technology may be useful in further elucidating the relationship between
      obesity and PCa progression.

PMID- 24571015
TI  - [Hygienic procedures].

PMID- 24571016
TI  - [Outpatient before inpatient].

PMID- 24571017
TI  - Author response.

PMID- 24571018
TI  - Author response.

PMID- 24571019
TI  - Reply: To PMID 23255692.

PMID- 24571020
TI  - Reply: To PMID 23942432.

PMID- 24571021
TI  - Reply: To PMID 23942401.

PMID- 24571022
TI  - Auditory hallucinations as ictal phenomena in a patient with voltage-gated
      potassium channel antibody-associated limbic encephalitis.
AB  - Limbic encephalitis involving anti-voltage-gated potassium channel antibodies
      (VGKC-LE) has become increasingly recognised, with seizures and psychotic
      features, such as hallucinations being typical clinical manifestations. Though
      the literature supports auditory hallucinations as ictal phenomena, there are no
      reported cases of these hallucinations correlating with electrographic seizure
      for this disease entity. Early recognition of auditory hallucinations as seizures
      could alter treatment and subsequently affect short-term outcomes in these
      patients. We report the case of a patient with auditory hallucinations and
      progressive cognitive decline, as well as serological evidence of VGKC
      antibodies, in whom ictal hallucinations were identified by continuous video-EEG
      monitoring. This case highlights the subtlety of this entity, in both clinical
      and electrographic detection. [Published with video sequences].

PMID- 24571023
TI  - Reply: To PMID 23502660.

PMID- 24571024
TI  - Reply to Schubert et al.: Regarding critique of highly multiplexed technologies.

PMID- 24571026
TI  - Mir-155, a central modulator of T-cell responses.
AB  - The activation of T cells is a tightly regulated process that has evolved to
      maximize protective immune responses to pathogens while minimizing damage to self
      tissues. A delicate balance of cell-intrinsic, costimulatory, and transcriptional
      pathways as well as micro-environmental cues such as local cytokines controls the
      magnitude and nature of T-cell responses in vivo. The discovery of functional
      small noncoding RNAs called micro-RNAs (miRNAs) has introduced new mechanisms
      that contribute to the regulation of protein translation and cellular responses
      to stimuli. miRNAs are short (approximately 22 bp) RNA species, which bind to
      mRNAs and suppress translation. Due to their short length and imperfect base
      pairing requirements, each miRNA has the potential to regulate various pathways
      through the translational inhibition of multiple mRNAs. The human and mouse
      genomes each encode hundreds of miRNAs, and studying the function of miRNAs has
      led to the realization that they play important roles in diverse biological
      processes from development and cancer to immunity. This review focuses on the
      function of mir-155 in T cells and the impact of this miRNA on autoimmunity,
      tumor immunity, and pathogen-induced immunity.

PMID- 24571025
TI  - Family transitions and changes in drinking from adolescence through mid-life.
AB  - AIMS: To examine how changes in social roles, particularly in the family, predict
      rises and falls in alcohol consumption from ages 16 to 50 years. DESIGN:
      Longitudinal data from the National Child Development Study. SETTING: The birth
      cohort includes 99% of British infants born in 1 week in 1958. Participants After
      initial assessment of 17,415 infants, the cohort was interviewed at ages 7, 11,
      16, 23, 33, 42, 46, and 50. This study uses the six adolescent to adult waves (n
      = 7212 women, 7377 men). MEASUREMENTS: Alcohol use [i.e. quantity consumed in
      past week and heavy daily drinking), symptoms of problem drinking (i.e. Cut-down,
      Annoyed, Guilt, Eye-opener (CAGE)] and social roles (i.e. union formation,
      parenthood and employment). FINDINGS: Estimates from fixed-effects models
      demonstrate that alcohol use is lower when women reside with child(ren) under age
      5, compared to occasions when they do not [estimate = -0.38, 95% confidence
      interval (CI) = -0.43, -0.32 for past week units; odds ratio (OR) = 0.47, CI =
      0.36, 0.62 for heavy-daily drinking; OR = 0.66, CI = 0.50, 0.87 for CAGE
      symptoms]. Associations are similar for men (estimate = -0.29, CI = -0.36, -0.23;
      OR = 0.64, CI = 0.53, 0.77; OR = 0.69, CI = 0.51, 0.94, respectively). When women
      and men are married, working and residing with young child(ren), past week units
      (estimate = -0.51, CI = -0.61, -0.41 for women; estimate = -0.34, CI = -0.44, 
      0.25 for men), heavy-daily drinking (OR = 0.49, CI = 0.30, 0.79 for women; OR =
      0.47, CI = 0.35, 0.64 for men) and CAGE (OR = 0.44, CI = 0.23, 0.83 for women; OR
      = 0.39, CI = 0.18, 0.82 for men) are lower compared to occasions when they are
      not in these roles. CONCLUSIONS: From late adolescence to mid-life, women and men
      in Britain are most at risk for higher levels of alcohol consumption and problem
      drinking when family roles are absent.

PMID- 24571027
TI  - Working memory impairment and cardiovascular hyperarousal in young primary
      insomniacs.
AB  - We investigated memory performance and cardiovascular activity in 13 primary
      insomniacs (PI) compared to 13 good sleepers (GS). Cardiovascular and hemodynamic
      measures, including heart rate, pre-ejection period, and blood pressure, were
      continuously recorded at rest and during two memory tasks. PI showed working
      memory impairment under high cognitive load, but performed as well as GS in an
      easy memory task. In addition, PI exhibited markers of hyperarousal both at rest
      and during the execution of the two tasks. However, we failed to find a clear-cut
      relationship between cardiovascular hyperarousal and cognitive performance in
      insomniacs. Our data provide further evidence of both cognitive impairment and
      cardiovascular hyperarousal in primary insomnia, while not supporting the
      hypothesis of hyperarousal as a compensatory mechanism to overcome cognitive
      challenges.

PMID- 24571028
TI  - HRT, body mass index and breast cancer risk.

PMID- 24571029
TI  - Menopausal hormone therapy and prevention of chronic diseases: IMS members react
      to the recent JAMA paper.

PMID- 24571030
TI  - Influence of recency and duration of glucocorticoid use on bone mineral density
      and risk of fractures.

PMID- 24571031
TI  - Keep your weight--don't miss breakfast.

PMID- 24571032
TI  - The importance of HT dose, formulation and route of delivery.

PMID- 24571033
TI  - Breast cancer risk and pretreatment estrogen levels.

PMID- 24571034
TI  - The value of repeat BMD testing in elderly people.

PMID- 24571035
TI  - Cognitive behavior therapy and hot flushes.

PMID- 24571036
TI  - American College of Cardiology/American Heart Association release new guideline
      for assessing cardiovascular risk in adults.

PMID- 24571037
TI  - American Heart Association late-breaking clinical trials 2013.

PMID- 24571038
TI  - Eating fish and atrial fibrillation.

PMID- 24571039
TI  - The author response.

PMID- 24571040
TI  - Reply from the authors.

PMID- 24571041
TI  - Goals for 2013 can still be met.

PMID- 24571042
TI  - Foreword. Evidence review: efficacy and reproducible compression of the KTwo
      bandage system.

PMID- 24571043
TI  - Efficacy and reproducible compression of KTwo.
AB  - To achieve good patient outcomes, clinicians must ensure that clinical decision
      making is informed by valid and reliable evidence. This review examines the
      evidence on the clinical efficacy and reproducibility of compression applied by
      the KTwo bandage system. Its aim is to describe the evidence, not critique it.
      However, it clearly shows there is a body of evidence, from simple comparative
      evaluations to a randomised controlled trial, demonstrating the effectiveness of
      this system

PMID- 24571044
TI  - Opportunity knocking?

PMID- 24571045
TI  - Building and sustaining a referral network.

PMID- 24571046
TI  - [Peer support: experiences and international perspectives].

PMID- 24571048
TI  - The intersection of ostomy and wound management, obesity, and associated science.

PMID- 24571049
TI  - Exploring workplace bullying in nursing.
AB  - Bullying in the nursing workplace has been identified as a factor that affects
      patient outcomes and increases occupational stress and staff turnover. The
      purpose of this project was to assess registered nurses' perceived exposure to
      workplace bullying. A convenience sample of a Pacific Northwest state
      professional nurses' association membership was solicited for this descriptive
      study using the Negative Acts Questionnaire-Revised (NAQ-R). Forty-eight percent
      of respondents admitted to being bullied in the workplace during the previous 6
      months, with respondents choosing "being ignored or excluded" as the most common
      negative experience in the workplace. The results of this study suggest that
      workplace bullying remains a problem for which reduction strategies must be
      devised as a means of retaining nurses and preventing adverse outcomes. One
      strategy shown to be effective in curbing bullying is assertiveness and
      aggression training for nurses.

PMID- 24571050
TI  - Personal protective equipment use among students with special health care needs
      reporting injuries in school-sponsored vocational, career, and technical
      education programs in New Jersey.
AB  - Students with special health care needs (SHCNs) and individualized education
      plans (IEPs) may be injured more often in vocational, career, and technical
      education (CTE) programs. No research to date considers personal protective
      equipment (PPE) use among students with SHCNs in school-based programs reporting
      injuries to agencies. Data from 1999 to 2011 on PPE use among injured students in
      CTE programs in public schools and private secondary schools for the disabled
      were analyzed; students with SHCNs were distinguished by IEP status within New
      Jersey Safe Schools surveilance data. Among students with IEPs using PPE, 36% of
      injuries occurred to body parts PPE was meant to protect. Likely injury types
      were cuts-lacerations and burns for students with IEPs using PPE and cuts
      lacerations and sprains for students with IEPs not using PPE. Females with IEPs
      using PPE were injured less often than males across ages. Results suggested
      students with SHCNs with IEPs need further job-related training with increased
      emphasis on properly selecting and fitting PPE.

PMID- 24571052
TI  - Firefighters' cardiovascular risk behaviors.
AB  - Cardiac events are strongly associated with line-of-duty deaths among
      firefighters. The frequency with which firefighters succumb to cardiovascular
      events while on duty is well documented. Many firefighters have undiagnosed or
      undertreated hypertension, hyperlipidemia, and obesity, as well as poor dietary
      habits and marginal physical fitness. Extremely high heart rates while engaged in
      fire suppression increase the risk for cardiovascular risk within the fire
      service. Cultural factors such as shift work and crew cohesion create multiple
      levels of influence on firefighters' decisions about engaging in positive health
      behaviors. This review highlights the significance of primordial and primary
      prevention of cardiovascular diseases that is culturally congruent with the fire
      service.

PMID- 24571051
TI  - Resident aggression toward staff at a center for the developmentally disabled.
AB  - Few studies have examined factors contributing to nonfatal assaults to staff
      working in residential care facilities. The authors evaluated resident assaults
      toward direct care/nursing staff at an intermediate Care Facility for Individuals
      with Mental Retardation (ICF/MR), which included observations of work areas,
      employee interviews, calculation of injury and assault rates for 2004 to 2007
      from Occupational Safety and Health Administration Logs, and review of state
      ICP/MR guidelines. Most staff interviewed reported having been injured during
      physical restraint of a resident and the average rate of injury from assault at
      the center evaluated was higher than the average national rates for the health
      care and social assistance sector for the same time period. The center lacked
      policies and developing a post-incident response and evaluation program to assist
      staff in coping with the consequences of assault and/or occupational injury.

PMID- 24571053
TI  - Structurally defined nanoscale sheets from self-assembly of collagen-mimetic
      peptides.
AB  - We report the design of two collagen-mimetic peptide sequences, NSI and NSII,
      that self-assemble into structurally defined nanoscale sheets. The underlying
      structure of these nanosheets can be understood in terms of the layered packing
      of collagen triple helices in two dimensions. These nanosheet assemblies
      represent a novel morphology for collagen-based materials, which, on the basis of
      their defined structure, may be envisioned as potentially biocompatible platforms
      for controlled presentation of chemical functionality at the nanoscale. The
      molecularly programmed self-assembly of peptides NSI and NSII into nanosheets
      suggests that sequence-specific macromolecules offer significant promise as
      design elements for two-dimensional (2D) assemblies. This investigation provides
      a design rubric for fabrication of structurally defined, peptide-based nanosheets
      using the principles of solution-based self-assembly facilitated through
      complementary electrostatic interactions. 

PMID- 24571054
TI  - Molecular determinants of a regulatory prolyl isomerization in the signal adapter
      protein c-CrkII.
AB  - The cellular CT10 regulator of kinase protein (c-CrkII) transmits signals from
      oncogenic tyrosine kinases to cellular targets. Nuclear magnetic resonance
      studies had suggested that in chicken c-CrkII a native state prolyl cis-trans
      isomerization is involved in signal propagation. Corresponding evidence for the
      closely related human c-CrkII was not obtained. Here we analyzed the kinetics of
      folding and substrate binding of the two homologues and found that cis-trans
      isomerization of Pro238 determines target binding in chicken but not in human c
      CrkII. A reciprocal mutational analysis uncovered residues that determine the
      isomeric state at Pro238 and transmit it to the binding site for downstream
      target proteins. The transfer of these key residues to human c-CrkII established
      a regulatory proline switch in this protein, as well. We suggest that Pro238
      isomerization extends the lifetime of the signaling-active state of c-CrkII and
      thereby functions as a long-term molecular storage device. 

PMID- 24571055
TI  - New solvates of an old drug compound (phenobarbital): structure and stability.
AB  - The solvent formation of phenobarbital, an important drug compound with an
      unusually complex polymorphic behavior, was studied in detail. Monosolvates with
      acetonitrile, nitromethane, dichloromethane, and 1,4-dioxane were produced and
      characterized by single-crystal and powder X-ray diffraction, thermoanalytical
      methods, FT-IR, Raman, and solid-state NMR spectroscopy. Thermal desolvation of
      these compounds yields mainly mixtures of polymorphs III, II, and I. At a low
      relative humidity (25  degrees C) the solvates transform to polymorph III, and at
      higher relative humidity the monohydrate and the metastable polymorphs IV and VI
      can be present as additional desolvation products. These results highlight the
      potential complexity of desolvation reactions and illustrate that a tight control
      of ambient conditions is a prerequisite for the production of phase-pure raw
      materials of drug compounds. Transformation in aqueous media results in the
      monohydrate. Below room temperature, the 1,4-dioxane monosolvate undergoes a
      reversible single-crystal-to-single-crystal phase transition due to the
      ordering/disordering of 50% of its solvent molecules. Dipolar-dephasing NMR
      experiments show that the solvent molecules are relatively mobile. Deuterium NMR
      spectra reinforce that conclusion for the dioxane solvent molecules. The crystal
      structure of an elusive 1,4-dioxane hemisolvate was also determined. This study
      clearly indicates the existence of "transient solvates" of phenobarbital. The
      formation of unstable phases of this kind must be considered in order to better
      understand how different solvents affect the crystallization of specific
      polymorphs. 

PMID- 24571056
TI  - PIFs get BRright: PHYTOCHROME INTERACTING FACTORs as integrators of light and
      hormonal signals.
AB  - Light and temperature, in coordination with the endogenous clock and the hormones
      gibberellin (GA) and brassinosteroids (BRs), modulate plant growth and
      development by affecting the expression of multiple cell wall- and auxin-related
      genes. PHYTOCHROME INTERACTING FACTORS (PIFs) play a central role in the
      activation of these genes, the activity of these factors being regulated by the
      circadian clock and phytochrome-mediated protein destabilization. GA signaling is
      also integrated at the level of PIFs; the DELLA repressors are found to bind
      these factors and impair their DNA-binding ability. The recent finding that PIFs
      are co-activated by BES1 and BZR1 highlights a further role of these regulators
      in BR signal integration, and reveals that PIFs act in a concerted manner with
      the BR-related BES1/BZR1 factors to activate auxin synthesis and transport at the
      gene expression level, and synergistically activate several genes with a role in
      cell expansion. Auxins feed back into this growth regulatory module by inducing
      GA biosynthesis and BES1/BZR1 gene expression, in addition to directly regulating
      several of these growth pathway gene targets. An exciting challenge in the future
      will be to understand how this growth program is dynamically regulated in time
      and space to orchestrate differential organ expansion and to provide plants with
      adaptation flexibility.

PMID- 24571057
TI  - Changes in arterial function in a mouse model of human familial
      hypercholesterolaemia.
AB  - AIM: Atherosclerosis is the most common cause of cardiovascular disease. The ApoB
      mouse is a model for human familial hypercholesterolaemia and has a lipoprotein
      profile similar to that of humans with atherosclerosis. Therefore, it is a
      suitable model to investigate the changes in vasoreactivity during atherogenesis.
      This study investigates contractile and dilatative properties of arteries in this
      model in relation to age. METHODS: Male ApoB mice and B6, wild-type (WT), mice
      were examined at age four or 18 months. Isometric measurements of 2-mm ring
      preparations of the aorta thoracica were performed using a wire myograph.
      Histological and biochemical methods served to determine atherosclerosis, lipid
      status and endothelial markers respectively. RESULTS: Morphometric analysis
      showed that all old ApoB mice had severe atherosclerosis in the aorta.
      Atherosclerotic alteration of the aorta of the ApoB mice coincided with a
      diminished vasodilatation to acetylcholine. The phenylephrine response was
      significantly attenuated already to the same degree in the non-atherosclerotic
      aorta of the young ApoB mice as in the atherosclerotic aorta of the older ApoB
      mice. Serum parameters showed a rise in total cholesterol and triglycerides in
      the ApoB strain compared to WT mice. Soluble intercellular adhesion molecule
      (sICAM)-1 and soluble vascular adhesion molecule (sVCAM)-1 were increased in old
      compared to young ApoB mice. CONCLUSION: The study shows that reduced
      acetylcholine-induced dilatation is related to the presence of atherosclerosis in
      old ApoB mice. Remarkably, the impaired vessel reactivity to phenylephrine
      already in young ApoB mice indicates early changes in vascular function in this
      model.

PMID- 24571058
TI  - Review of high-dose intravenous vitamin C as an anticancer agent.
AB  - In the 1970s, Pauling and Cameron reported increased survival of patients with
      advanced cancer treated with high-dose intravenous (IV) vitamin C (L-ascorbate,
      ascorbic acid). These studies were criticized for their retrospective nature and
      lack of standardization of key prognostic factors including performance status.
      Subsequently, several well-designed randomized controlled trials failed to
      demonstrate a significant survival benefit, although these trials used high-dose
      oral vitamin C. Marked differences are now recognized in the pharmacokinetics of
      vitamin C with oral and IV administration, opening the issue of therapeutic
      efficacy to question. In vitro evidence suggests that vitamin C functions at low
      concentrations as an antioxidant but may have pro-oxidant activity at high
      concentrations. The mechanism of its pro-oxidant action is not fully understood,
      and both intra- and extracellular mechanisms that generate hydrogen peroxide have
      been proposed. It remains to be proven whether vitamin C-induced reactive oxygen
      species occur in vivo and, if so, whether this will translate to a clinical
      benefit. Current clinical evidence for a therapeutic effect of high-dose IV
      vitamin C is ambiguous, being based on case series. The interpretation and
      validation of these studies is hindered by limited correlation of plasma vitamin
      C concentrations with response. The methodology exists to determine if there is a
      role for high-dose IV vitamin C in the treatment of cancer, but the limited
      understanding of its pharmacodynamic properties makes this challenging.
      Currently, the use of high-dose IV vitamin C cannot be recommended outside of a
      clinical trial. 

PMID- 24571059
TI  - Economic analysis of aprepitant-containing regimen to prevent chemotherapy
      induced nausea and vomiting in patients receiving highly emetogenic chemotherapy
      in Hong Kong.
AB  - AIM: We aim to evaluate the cost effectiveness of aprepitant-containing regimens
      for the prevention of chemotherapy-induced nausea and vomiting (CINV) among
      patients receiving high emetogenic chemotherapy (HEC) in Hong Kong. METHODS: Both
      cost-effectiveness and cost-utility analyses were conducted utilizing a decision
      analytic model to measure the economic costs and clinical outcomes associated
      with the aprepitant-containing regimen versus a standard regimen in the
      prevention of CINV. Analyses were conducted on the basis of four published double
      blind randomized clinical trials involving different usages of serotonin receptor
      antagonists. RESULTS: The use of aprepitant-containing regimens is associated
      with an improvement in quality-adjusted life years (QALYs) compared with non
      aprepitant regimens. For cisplatin-based chemotherapy, the incremental cost per
      QALY gained is HKD 239,644 (1 USD approximates HKD 7.8) when ondansetron is
      administered on day 1 only. The incremental cost per QALY is HKD 440,950 when
      ondansetron is used on day 1 to 4. For anthracycline and cyclophosphamide
      chemotherapy, the aprepitant-containing regimen is associated with incremental
      cost of HKD 195,442 per QALY gained. Similar results were obtained when other
      5HT3 receptor antagonists are used. The use of aprepitant was associated with
      higher cost of drug but lower costs of emesis-related management. With the cost
      effectiveness threshold set at the World Health Organization endorsed criteria of
      three times gross domestic product (GDP) per capita (three times GDP per capita
      in Hong Kong in 2011 is HKD 798,078), the current analyses showed that the
      aprepitant-containing regimen was cost-effective. CONCLUSIONS: In patients
      undergoing HEC, the use of aprepitant as the anti-emetic is cost-effective in
      Hong Kong.

PMID- 24571062
TI  - Comparison between the combination of gabapentin, ketamine, lornoxicam, and local
      ropivacaine and each of these drugs alone for pain after laparoscopic
      cholecystectomy: a randomized trial.
AB  - BACKGROUND: The main purpose of the study was to test whether the combination of
      gabapentin (600 mg 4 hours before surgery, 600 mg after 24 hours), ketamine (0.3
      mg/kg before anesthesia), lornoxicam (8 mg before anesthesia and 8 mg/12 hours),
      and local ropivacaine (5 mL 7.5% at insertion sites) provides superior analgesia
      to each of these drugs alone in the first 24 hours after laparoscopic
      cholecystectomy. The secondary purpose was to examine whether this combination
      has less opioid-related side effects. METHODS: This was a 2-center randomized
      placebo-controlled trial. One hundred forty-eight patients, between 18 and 70
      years of age, were randomly assigned to 6 groups (28 in each group) with the use
      of computer software: A(gabapentin/ketamine/lornoxicam/ropivacaine);
      B(gabapentin/placebo/placebo/placebo); C (placebo/ketamine/placebo/placebo); D
      (placebo/placebo/lornoxicam/placebo); E (placebo/placebo/placebo/ropivacaine);
      and F (placebo/placebo/placebo/placebo). Only the principal investigator was
      aware of patients' allocation and provided drugs and placebo in covered prefilled
      syringes. The primary outcome of the study was the 24-hour morphine consumption.
      Secondary outcomes were frequency of opioid-related side effects (nausea,
      vomiting, sedation, pruritus, and dysuria). RESULTS: Only groups A (6.4 mg), B
      (9.46 mg), and D (9.36 mg) had lower morphine consumption than control group
      (20.29 mg) (P < 0.001, P = 0.01, and P = 0.008, respectively). Group A was not
      different from B and D (P = 0.92, P = 0.93). The only difference was in episodes
      of nausea between groups A (n = 5) and the control group (n = 12) (P = 0.018).
      CONCLUSION: The combination of gabapentin, ketamine, lornoxicam, and local
      ropivacaine does not provide superior analgesia than gabapentin alone or
      lornoxicam alone after laparoscopic cholecystectomy. The combination reduces only
      the frequency of postoperative nausea, but larger studies are needed for safer
      results.

PMID- 24571063
TI  - Electroconvulsive therapy reappraised.

PMID- 24571064
TI  - A synthesis of the ABC tricyclic core of the clionastatins serves to corroborate
      their proposed structures.
AB  - A synthesis of the ABC tricyclic ring system of the clionastatins, an unusual
      pair of highly chlorinated androstane steroids, has been accomplished. This work
      provides strong support for the original structural proposal. An unexpected
      substrate-dependent reversal in alkene chlorination diastereoselectivity was
      critical to success. This approach should be amenable to an eventual
      enantioselective synthesis of the natural products themselves. 

PMID- 24571065
TI  - Aflatoxin: does it contribute to an increase in HIV viral load?

PMID- 24571066
TI  - An insight into flaviviral budding: a need to know more.

PMID- 24571068
TI  - Pseudotypes: your flexible friends.
AB  - Pseudotype viruses: applications and troubleshooting' (EuroSciCon 2013), a 1-day
      conference held at Cineworld: The O2 (London, UK) on 2 October 2013, focused on
      the technique of pseudotyping enveloped viruses (for a review of the technique,
      see [1]). The talks and posters covered the challenges and successes of
      pseudotyping viruses from a broad range of families (Retroviridae, Flaviviridae,
      Orthomyxoviridae, Bunyaviridae and Rhabdoviridae) for a variety of applications.
      The conference was chaired by Nigel Temperton, University of Kent (UK), who
      placed a strong emphasis on using this event to explore the technical challenges
      of pseudotyping viruses, especially during the poster and afternoon question and
      answer sessions.

PMID- 24571069
TI  - Antifungal activity of phenolic compounds identified in flowers from North
      Eastern Portugal against Candida species.
AB  - AIM: To evaluate the antifungal effect of gallic acid, catechin, luteolin and
      quercetin, phenolic compounds identified from flowers of North Eastern Portugal,
      against Candida planktonic and biofilm cells. MATERIALS & METHODS: The MICs were
      determined in Candida planktonic cells and the effect of phenolic compounds on
      Candida biofilms was assessed through quantification of colony-forming units.
      RESULTS: MIC values demonstrated that gallic acid presented the highest effect
      against all Candida species. Catechin showed a similar effect against Candida
      albicans American Type Culture Collection (ATCC) 90028 cells. In addition, gallic
      acid and quercetin had demonstrated only a minimal effect against Candida species
      biofilms. CONCLUSION: Gallic acid affected the growth of the different planktonic
      Candida species in all concentrations used; still, catechin showed a similar
      effect against C. albicans ATCC 90028 and Candida glabrata ATCC 2001 cells. In
      addition, only gallic acid and quercetin demonstrated a slight effect against all
      Candida species biofilms.

PMID- 24571071
TI  - Correlation between Candida albicans biofilm formation and invasion of the
      invertebrate host Galleria mellonella.
AB  - AIM: The aim of our study was to investigate whether biofilm production by
      Candida albicans clinical isolates could be a hallmark of virulence in vivo.
      MATERIALS & METHODS: Twenty clinical isolates of C. albicans were examined via
      histological studies on larvae infected with various fungal doses (from 10(3) to
      10(5) CFU/larva) of biofilm producer and nonproducer strains. RESULTS: The poor
      prognostic role of infection due to a biofilm-producing isolate was confirmed by
      the Wald test (hazard ratio: 2.63; 95% CI: 2.03-3.41). Histological examinations
      at 24 h showed a strong innate immune response, with evidence of melanization for
      both infection groups. However, at 48 h, we found huge differences in
      filamentation and tissue invasion capability between biofilm nonproducing and
      producing isolates, the latter being highly organized into biofilm and invading
      the larval intestinal tract. Invasion corroborated survival data. CONCLUSION: The
      histological results demonstrate that the production of biofilm could enhance the
      invasiveness of C. albicans.

PMID- 24571072
TI  - Biofilm-based infections in long-term care facilities.
AB  - The recent trend in the early admittance to long-term care facilities (LTCFs) of
      severely injured patients transferred from general hospitals has given a new
      dynamic to the incidence of healthcare-associated infections, including biofilm
      based infections related to the implant of urinary and intravascular catheters,
      and the onset of pressure ulcers. Catheter-associated urinary tract infections
      lead in most of the surveys on LTCFs, approximately 80% of urinary tract
      infections in these settings being due to the short- or long-term insertion of a
      urinary catheter. Furthermore, the implantation of intravascular catheters is
      often responsible for catheter-related bloodstream infections caused by the
      development of an intraluminal biofilm. Pressure ulcers, frequently occurring in
      bedridden patients admitted to LTCFs, are also susceptible to infection by
      biofilm-growing aerobic and anaerobic bacteria, the biofilm formation on the
      wound being the main reason for its delayed healing. 

PMID- 24571070
TI  - Cryptococcus neoformans glucuronoxylomannan fractions of different molecular
      masses are functionally distinct.
AB  - AIMS: Glucuronoxylomannan (GXM) is the major polysaccharide component of
      Cryptococcus neoformans. We evaluated in this study whether GXM fractions of
      different molecular masses were functionally distinct. MATERIALS & METHODS: GXM
      samples isolated from C. neoformans cultures were fractionated to generate
      polysaccharide preparations differing in molecular mass. These fractions were
      used in experiments focused on the association of GXM with cell wall components
      of C. neoformans, as well as on the interaction of the polysaccharide with host
      cells. RESULTS & CONCLUSION: GXM fractions of variable molecular masses bound to
      the surface of a C. neoformans acapsular mutant in a punctate pattern that is in
      contrast to the usual annular pattern of surface coating observed when GXM
      samples containing the full molecular mass range were used. The polysaccharide
      samples were also significantly different in their ability to stimulate cytokine
      production by host cells. Our findings indicate that GXM fractions are
      functionally distinct depending on their mass.

PMID- 24571073
TI  - Is gonorrhea becoming untreatable?
AB  - An estimated 498 million new cases of curable sexually transmitted infections
      occur worldwide annually. Of these, 106 million are gonococcal infections,
      rendering gonorrhea the second most prevalent bacterial sexually transmitted
      infection after chlamydia. A decline in susceptibility to extended-spectrum
      cephalosporins, as well as treatment failures, have been identified worldwide.
      This, together with the associated epidemiological and socioeconomic burden, is
      of increasing concern. Currently, the effectiveness of antibiotic resistance
      control measures is limited. Barriers include the lack of therapeutic options,
      the difficulties of reducing high-risk sexual behavior and Neisseria
      gonorrhoeae's propensity to rapidly acquire resistance determinants. While the
      disease remains treatable for the moment, we need to anticipate and be prepared
      for the arrival and spread of untreatable gonorrhea by using a multifaceted
      approach and search for other, perhaps novel control strategies. 

PMID- 24571074
TI  - Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry: a
      new possibility for the identification and typing of anaerobic bacteria.
AB  - Anaerobic bacteria predominate in the normal flora of humans and are important,
      often life-threatening pathogens in mixed infections originating from the
      indigenous microbiota. The isolation and identification of anaerobes by
      phenotypic and DNA-based molecular methods at a species level is time-consuming
      and laborious. Following the successful adaptation of the matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry for the routine laboratory
      identification of bacteria, the extensive development of a database has been
      initiated to use this method for the identification of anaerobic bacteria. Not
      only frequently isolated anaerobic species, but also newly recognized and
      taxonomically rearranged genera and species can be identified using direct smear
      samples or whole-cell protein extraction, and even phylogenetically closely
      related species can be identified correctly by means of matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry. Typing of anaerobic
      bacteria on a subspecies level, determination of antibiotic resistance and direct
      identification of blood culture isolates will revolutionize anaerobe bacteriology
      in the near future. 

PMID- 24571075
TI  - On bacteriocin delivery systems and potential applications.
AB  - Bacteriocins are antimicrobial peptides produced by a variety of bacteria. These
      peptides can act as antibiotic synergists or alternatives to enhance the
      therapeutic effects of current infection treatments and decrease the prevalence
      of resistant strains. Two bacteriocins, namely nisin and pediocin PA-1, are
      currently being used by the food industry; however, the introduction of these and
      others into the biomedical industry, and further development of food
      applications, have been challenged by the slow development of reliable delivery
      systems. For bacteriocins, these systems rely on novel and pre-existing
      technologies. Many essential variables need to be accounted for to formulate
      successful delivery methods. In this review, documented and potential bacteriocin
      delivery systems are examined, with special attention paid to how those systems
      are being implemented in the food and medical industries. 

PMID- 24571076
TI  - Paper money and coins as potential vectors of transmissible disease.
AB  - Paper currency and coins may be a public health risk when associated with the
      simultaneous handling of food and could lead to the spread of nosocomial
      infections. Banknotes recovered from hospitals may be highly contaminated by
      Staphylococcus aureus. Salmonella species, Escherichia coli and S. aureus are
      commonly isolated from banknotes from food outlets. Laboratory simulations
      revealed that methicillin-resistant S. aureus can easily survive on coins,
      whereas E. coli, Salmonella species and viruses, including human influenza virus,
      Norovirus, Rhinovirus, hepatitis A virus, and Rotavirus, can be transmitted
      through hand contact. Large-scale, 16S rRNA, metagenomic studies and culturomics
      have the capacity to dramatically expand the known diversity of bacteria and
      viruses on money and fomites. This review summarizes the latest research on the
      potential of paper currency and coins to serve as sources of pathogenic agents. 

PMID- 24571077
TI  - Home dampness, childhood asthma, hay fever, and airway symptoms in Shanghai,
      China: associations, dose-response relationships, and lifestyle's influences.
AB  - Numerous studies of associations between dampness and respiratory diseases have
      been conducted, but their implications remain inconclusive. In this study of
      13,335 parent-reported questionnaires (response rate: 85.3%), we analyzed
      associations between home dampness and asthma and related symptoms in 4- to 6
      year-old children in a cross-sectional study of Shanghai. Indicators of home
      dampness were strongly and significantly associated with dry cough, wheeze, and
      rhinitis symptoms. In the current residence, children with visible mold spots
      (VMS) exposure had 32% higher risk of asthma (adjusted OR, 95% CI: 1.32, 1.07
      1.64); damp clothing and/or bedding (frequently) was strongly associated with dry
      cough (1.78, 1.37-2.30); condensation on windows was strongly associated with hay
      fever (1.60, 1.27-2.01). In the early-life residence, VMS or damp stains
      (frequently) were strongly associated with dry cough (2.20, 1.55-3.11) and
      rhinitis ever (1.57, 1.11-2.21). Associations between dampness and diseases among
      children with or without family history of atopy were similar. The total number
      of dampness indicators had strong dose-response relationships with investigated
      health outcomes. Actions, including opening windows of the child's room at night
      and cleaning the child's room frequently, could potentially mitigate 25% of home
      VMS, thereby preventing more than 1.5% of attributable risk of the studied
      symptoms. 

PMID- 24571078
TI  - Influence of hydrogen bonding on the structure of the (001) corundum-water
      interface. Density functional theory calculations and Monte Carlo simulations.
AB  - Density functional theory calculations and classical Monte Carlo simulations are
      applied to study the behavior of water in contact with a hydroxylated corundum
      (001) surface. Using DFT with periodic boundary conditions at T = 0 K, we
      systematically study the influence of the number of water molecules on the
      surface geometry and on the structure of the contact water layer. Only little
      effect of the thickness of the water layer on the geometry of the surface
      hydroxyl groups is observed. On the other hand, the molecules in the second layer
      have strong influence on the arrangement of water molecules in direct contact
      with the solid surface. In order to mimic macroscopic systems at room
      temperature, we perform inhomogeneous MC simulations of model corundum surface in
      contact with the water phase modeled by SPC/E model. The water molecules are
      classified according to their hydrogen-bonded partners into several groups. It is
      found that the preferential orientation of interfacial water molecules is
      primarily determined by the type of their hydrogen bonding. The hydroxyl groups
      at the corundum surface can serve as hydrogen bond donor or acceptor, depending
      on their orientation. No surface hydroxyls are found to coordinate two water
      molecules at the same time. On the other hand, water molecules coordinated by two
      different surface groups appear in MC simulations. 

PMID- 24571079
TI  - Chronic conditions policies: oral health, a felt absence.
AB  - The global health scenario shows an epidemic of non-communicable diseases that
      lead to long-term chronic conditions, some of which are incurable. Many
      infectious diseases, owing to their development and length, also generate chronic
      conditions. Similarly, non-morbid states, such as pregnancy, and some life cycles
      such as adolescence and ageing, follow the same logic. Among all these chronic
      conditions there is a significant interrelationship with oral health, both in
      parallel events and common risk factors. This article presents cross-sectional
      qualitative research into World Health Organisation recommended health policies
      to address chronic conditions. Several documents published by the organisation
      were analysed to verify the presence of references to oral health in relation to
      chronic conditions, particularly cardiovascular diseases and diabetes as these
      most frequently have oral manifestations. The analysis showed no significant
      references to oral health or its indicators within the published texts. The study
      recognises the value of the work developed by the World Health Organisation, as
      well as its worldwide leadership role in the development of health policies for
      chronic conditions. This article proposes a coalition of dentistry organisations
      that could, in a more forceful and collective way, advocate for a greater
      presence of oral health in drafting policies addressing chronic conditions. 

PMID- 24571080
TI  - Different dynamics of aquaporin 4 and glutamate transporter-1 distribution in the
      perineuronal and perivascular compartments during ischemic stroke.
AB  - Aquaporin-4 (AQP4) and glutamate transporter-1 (GLT-1) represent the major water
      and glutamate astrocyte buffering gateways in the brain. Utilizing perilesional
      ischemic human cortices, we have performed here for the first time an integrative
      assessment on both AQP4 and GLT-1, and on their proximity to blood vessels and
      neurons. Counting the relative number of AQP4+/-/GLT-1+/-/glial fibrillary acidic
      protein+/- cells showed that double-positive variants were overall most frequent,
      and their number tended to decrease from organized and recent perilesional
      cortices to controls. AQP4/GLT-1 colocalization showed higher coefficients for
      the perilesional cortices compared with controls, suggesting an increased
      water/glutamate-buffering capability. Distance frequency analysis of AQP4/GLT-1
      in relationship to neurons showed that both markers were concentrated at 20-40
      MUm around the perikarya; with AQP4 being more abundant in close proximity, these
      differences were not being driven by changes in neuropil density alone. Our study
      suggests a dual, simultaneous astrocytic function depending on the relative
      distance to neurons and vessels, with increased water and glutamate-buffering
      capability in the mid perineuronal space, and an increased water-buffering
      capability in the immediate perineuronal space, even higher than around vessels.
      Thus, adding specific AQP4/GLT-1 modulator agents selectively depending on the
      acute/chronic phase of stroke might increase the efficacy of existing treatments.

PMID- 24571081
TI  - Measuring the effectiveness of interventions for children with cerebral palsy.

PMID- 24571082
TI  - A Bayesian localized conditional autoregressive model for estimating the health
      effects of air pollution.
AB  - Estimation of the long-term health effects of air pollution is a challenging
      task, especially when modeling spatial small-area disease incidence data in an
      ecological study design. The challenge comes from the unobserved underlying
      spatial autocorrelation structure in these data, which is accounted for using
      random effects modeled by a globally smooth conditional autoregressive model.
      These smooth random effects confound the effects of air pollution, which are also
      globally smooth. To avoid this collinearity a Bayesian localized conditional
      autoregressive model is developed for the random effects. This localized model is
      flexible spatially, in the sense that it is not only able to model areas of
      spatial smoothness, but also it is able to capture step changes in the random
      effects surface. This methodological development allows us to improve the
      estimation performance of the covariate effects, compared to using traditional
      conditional auto-regressive models. These results are established using a
      simulation study, and are then illustrated with our motivating study on air
      pollution and respiratory ill health in Greater Glasgow, Scotland in 2011. The
      model shows substantial health effects of particulate matter air pollution and
      nitrogen dioxide, whose effects have been consistently attenuated by the
      currently available globally smooth models.

PMID- 24571083
TI  - Activation of microglia and induction of pro-inflammatory cytokines in the
      hippocampus of type 2 diabetic rats.
AB  - OBJECTIVES: The majority of immune cells in the brain are comprised of microglia,
      which undergo morphological changes when activated to remove damaged neurons and
      infectious agents from the brain tissue. In this study, we investigated the
      effects of type 2 diabetes on microglial activation and the subsequent secretion
      of pro-inflammatory cytokines, such as interferon-gamma (IFN-gamma) and
      interleukin-1beta (IL-1beta), in the hippocampus using Zucker diabetic fatty
      (ZDF) rats and Zucker lean control (ZLC) rats at various diabetic stages.
      METHODS: Zucker lean control and Zucker diabetic fatty rats were sacrificed at 12
      (early diabetic stage), 20, or 30 weeks of age (chronic diabetic stage), and the
      hippocampus was obtained via transcardiac perfusion or dissection for
      immunohistochemistry and western blot analysis, respectively. RESULTS: Zucker
      diabetic fatty rats demonstrated significantly higher glucose levels at 12 and 30
      weeks of age compared to ZLC rats. Microglia immunoreactive to ionized calcium
      binding adapter molecule 1 (Iba-1) had hypertrophied cytoplasm with retracted
      processes at 30 weeks of age. In contrast, Iba-1-immunoreactive microglia
      displayed similar morphology in ZDF and ZLC rats at 12 and 20 weeks of age.
      Similarly, IFN-gamma and IL-1beta protein levels were significantly increased in
      ZDF rats compared to ZLC rats at 30 weeks of age, but not at 12 and 20 weeks of
      age. Interleukin-1beta immunoreactivity in the ZDF rats predominantly increased
      in the dentate gyrus and CA1 region of the hippocampus compared to that of ZLC
      rats at 30 weeks of age. In addition, IL-1beta immunoreactive structures in ZDF
      rats at 30 weeks of age were detected near the astrocytes and microglia.
      CONCLUSION: These results suggest that chronic diabetes activates microglia and
      significantly increases pro-inflammatory cytokine levels in the hippocampus.

PMID- 24571084
TI  - When tonic cardiac vagal tone predicts changes in phasic vagal tone: the role of
      fear and perceptual load.
AB  - We examined the relationship between tonic--a correlate of self-regulatory
      functioning--and phasic cardiac vagal activity (indexed by heart rate
      variability; HRV) during a selective attentional task with varying levels of
      load. Participants detected a target letter among letter strings superimposed on
      either fearful or neutral face distractors. Letter strings consisted of six
      target letters under low load and one target letter and five nontarget letters
      under high load. With fearful distractors, lower tonic HRV was associated with
      phasic HRV suppression, suggesting an autonomic stress response under both low
      and high load. In contrast, higher tonic HRV was associated with phasic HRV
      enhancement, suggesting greater self-regulatory effort under low load and an
      absence of phasic HRV suppression under high load. The current research suggests
      that tonic cardiac vagal tone is associated with the ability to flexibly adapt
      autonomic responses.

PMID- 24571086
TI  - Antibacterial activity of lichen secondary metabolite usnic acid is primarily
      caused by inhibition of RNA and DNA synthesis.
AB  - Usnic acid, a compound produced by various lichen species, has been demonstrated
      previously to inhibit growth of different bacteria and fungi; however, mechanism
      of its antimicrobial activity remained unknown. In this report, we demonstrate
      that usnic acid causes rapid and strong inhibition of RNA and DNA synthesis in
      Gram-positive bacteria, represented by Bacillus subtilis and Staphylococcus
      aureus, while it does not inhibit production of macromolecules (DNA, RNA, and
      proteins) in Escherichia coli, which is resistant to even high doses of this
      compound. However, we also observed slight inhibition of RNA synthesis in a Gram
      negative bacterium, Vibrio harveyi. Inhibition of protein synthesis in B.
      subtilis and S. aureus was delayed, which suggest indirect action (possibly
      through impairment of transcription) of usnic acid on translation. Interestingly,
      DNA synthesis was halted rapidly in B. subtilis and S. aureus, suggesting
      interference of usnic acid with elongation of DNA replication. We propose that
      inhibition of RNA synthesis may be a general mechanism of antibacterial action of
      usnic acid, with additional direct mechanisms, such as impairment of DNA
      replication in B. subtilis and S. aureus. 

PMID- 24571087
TI  - Tumors with a more complex genome have a higher frequency of HLA class I total
      loss: a unifying pan-cancer hypothesis.

PMID- 24571085
TI  - Conditional expression of apical membrane antigen 1 in Plasmodium falciparum
      shows it is required for erythrocyte invasion by merozoites.
AB  - Malaria is caused by obligate intracellular parasites, of which Plasmodium
      falciparum is the most lethal species. In humans, P.  falciparum merozoites
      (invasive forms of the parasite) employ a host of parasite proteins to rapidly
      invade erythrocytes. One of these is the P.  falciparum apical membrane antigen 1
      (PfAMA1) which forms a complex with rhoptry neck proteins at the tight junction.
      Here, we have placed the Pfama1 gene under conditional control using dimerizable
      Cre recombinase (DiCre) in P.  falciparum. DiCre-mediated excision of the loxP
      flanked Pfama1 gene results in approximately 80% decreased expression of the
      protein within one intraerythrocytic growth cycle. This reduces growth by 40%,
      due to decreased invasion efficiency characterized by a post-invasion defect in
      sealing of the parasitophorous vacuole. These results show that PfAMA1 is an
      essential protein for merozoite invasion in P.  falciparum and either directly or
      indirectly plays a role in resealing of the red blood cell at the posterior end
      of the invasion event.

PMID- 24571089
TI  - Possible benefits of catheters with lateral holes in coronary thrombus
      aspiration: a computational study for different clot viscosities and vacuum
      pressures.
AB  - According to a number of clinical studies, coronary aspiration catheters are
      useful tools to remove a thrombus (blood clot) blocking a coronary artery.
      However, these thrombectomy devices may fail to remove the blood clot entirely.
      Few studies have been devoted to a systematic analysis of factors affecting clot
      aspiration. The geometric characteristics of the aspiration catheter, the
      physical properties of the thrombus, and the applied vacuum pressure are crucial
      parameters. In this study, the aspiration of a blood clot blocking a coronary
      bifurcation is computationally simulated. The clot is modeled as a highly viscous
      fluid, and a two-phase (blood and clot) problem is solved. The effects of
      geometric variations in the tip of the coronary catheter, including lateral hole
      size and location, are investigated considering different aspiration pressures
      and clot viscosities. A Bird-Carreau model is adopted for blood viscosity, while
      a power law model is used to describe the clot rheology. Computational results
      for blood clot aspiration show that the presence of holes in the lateral part of
      the tip of the catheter can be beneficial depending on clot viscosity, hole
      features, and applied aspiration pressure. In general, the holes are beneficial
      when the clot viscosity is low, while aspiration catheters without any extra
      lateral holes exhibit better performance for higher clot viscosity. However, when
      higher aspiration pressures are applied, the catheters tend to behave relatively
      similarly in removing clots with various viscosities, reducing the role of the
      clot viscosity. 

PMID- 24571088
TI  - Comparative genomics of type VI secretion systems in strains of Pantoea ananatis
      from different environments.
AB  - BACKGROUND: The Type VI secretion system (T6SS) has been identified in several
      different bacteria, including the plant pathogenPantoea ananatis. Previous in
      silico analyses described three different T6SS loci present in the pathogenic
      strain of P. ananatis LMG 20103. This initial investigation has been extended to
      include an additional seven sequenced strains of P. ananatis together with 39
      strains from different ecological niches. Comparative and phylogenetic analyses
      were used to investigate the distribution, evolution, intra-strain variability
      and operon structure of the T6SS in the sequenced strains. RESULTS: Three
      different T6SS loci were identified in P. ananatis strain LMG 20103 and
      designated PA T6SS 1-3. PA T6SS-1 was present in all sequenced strains of P.
      ananatis and in all 39 additional strains examined in this study. In addition, PA
      T6SS-1 included all 13 core T6SS genes required for synthesis of a functional
      T6SS. The plasmid-borne PA T6SS-2 also included all 13 core T6SS genes but was
      restricted to only 33% (15/46) of the strains examined. In addition, PA T6SS-2
      was restricted to strains of P. ananatis isolated from symptomatic plant
      material. This finding raises the possibility of an association between PA T6SS-2
      and either pathogenicity or host specificity. The third cluster PA T6SS-3 was
      present in all strains analyzed in this study but lacked 11 of the 13 core T6SS
      genes suggesting it may not encoded a functional T6SS. Inter-strain variability
      was also associated with hcp and vgrG islands, which are associated with the T6SS
      and encode a variable number of proteins usually of unknown function. These
      proteins may play a role in the fitness of different strains in a variety of
      ecological niches or as candidate T6SS effectors. Phylogenetic analysis indicated
      that PA T6SS-1 and PA T6SS-2 are evolutionarily distinct. CONCLUSION: Our
      analysis indicates that the three T6SSs of P. ananatis appear to have been
      independently acquired and may play different roles relating to pathogenicity,
      host range determination and/or niche adaptation. Future work will be directed
      toward understanding the roles that these T6SSs play in the biology of P.
      ananatis.

PMID- 24571090
TI  - Comparative studies of cytotoxic and apoptotic properties of different extracts
      and the essential oil of Lavandula angustifolia on malignant and normal cells.
AB  - Lavender (Lavandula angustifolia Mill.) is a bush-like shrub from Lamiaceae. The
      herb has been used in alternative medicine for several centuries. In this study,
      the cytotoxicity and the mechanisms of cell death induced by 3 different extracts
      of aerial parts and the essential oil of L. angustifolia were compared in normal
      and cancerous human cells. Malignant (HeLa and MCF-7 cell lines) and nonmalignant
      (human fibroblasts) cells were incubated with different concentrations of the
      plant extracts. Cell viability was quantified by MTS assay. Apoptotic cells were
      determined using propidium iodide staining of DNA fragmentation by flow cytometry
      (sub-G1 peak). The molecules as apoptotic signal translation, including Bax and
      cleaved PARP, were identified by Western blot. Ethanol and n-hexane extracts and
      essential oil exhibited significant cytotoxicity to malignant cells but marginal
      cytotoxicity to human fibroblasts in vitro and induced a sub-G1 peak in flow
      cytometry histogram of treated cells compared to the control. Western blot
      analysis demonstrated that EtOH and n-hexane extracts upregulated Bax expression,
      also it induced cleavage of PARP in HeLa cells compared to the control. In
      conclusion, L. angustifolia has cytotoxic and apoptotic effects in HeLa and MCF-7
      cell lines, and apoptosis is proposed as the possible mechanism of action. 

PMID- 24571092
TI  - Urban stormwater runoff nitrogen composition and fate in bioretention systems.
AB  - Multiple chemical forms of nitrogen in urban stormwater make its management
      challenging. Sixteen storm events were monitored and analyzed for total nitrogen
      (TN), particulate organic nitrogen (PON), nitrate (NO3-N), nitrite (NO2-N),
      ammonium (NH3-N), and dissolved organic nitrogen (DON) in stormwater runoff and
      in treated discharge through a conventional bioretention cell. Influent PON can
      be effectively removed via bioretention sedimentation/filtration, NH3-N by ion
      exchange/sorption, and NO2-N by oxidation. However, significant DON and NO3-N
      leached from the bioretention cell, resulting in only 9% net overall TN
      concentration reduction. Captured PON and vegetation detritus in the bioretention
      cell can be leached as DON or mineralized into NO3-N. The effluent N is dominated
      by NO3-N (46%) and DON (42%). Therefore, in addition to creating denitrification
      conditions for NO3-N, preventing DON leaching is also critical for effective
      nitrogen removal though bioretention systems. The bioretention cell exhibited a
      moderate mass load reduction for TN (41%), which mainly results from runoff
      volume reduction. 

PMID- 24571094
TI  - Special issue on computations in oscillating neuronal networks.

PMID- 24571091
TI  - Genome and secretome analysis of the hemibiotrophic fungal pathogen,
      Moniliophthora roreri, which causes frosty pod rot disease of cacao: mechanisms
      of the biotrophic and necrotrophic phases.
AB  - BACKGROUND: The basidiomycete Moniliophthora roreri is the causal agent of Frosty
      pod rot (FPR) disease of cacao (Theobroma cacao), the source of chocolate, and
      FPR is one of the most destructive diseases of this important perennial crop in
      the Americas. This hemibiotroph infects only cacao pods and has an extended
      biotrophic phase lasting up to sixty days, culminating in plant necrosis and
      sporulation of the fungus without the formation of a basidiocarp. RESULTS: We
      sequenced and assembled 52.3 Mb into 3,298 contigs that represent the M. roreri
      genome. Of the 17,920 predicted open reading frames (OFRs), 13,760 were validated
      by RNA-Seq. Using read count data from RNA sequencing of cacao pods at 30 and 60
      days post infection, differential gene expression was estimated for the
      biotrophic and necrotrophic phases of this plant-pathogen interaction. The
      sequencing data were used to develop a genome based secretome for the infected
      pods. Of the 1,535 genes encoding putative secreted proteins, 1,355 were
      expressed in the biotrophic and necrotrophic phases. Analysis of the data
      revealed secretome gene expression that correlated with infection and
      intercellular growth in the biotrophic phase and invasive growth and plant
      cellular death in the necrotrophic phase. CONCLUSIONS: Genome sequencing and RNA
      Seq was used to determine and validate the Moniliophthora roreri genome and
      secretome. High sequence identity between Moniliophthora roreri genes and
      Moniliophthora perniciosa genes supports the taxonomic relationship with
      Moniliophthora perniciosa and the relatedness of this fungus to other
      basidiomycetes. Analysis of RNA-Seq data from infected plant tissues revealed
      differentially expressed genes in the biotrophic and necrotrophic phases. The
      secreted protein genes that were upregulated in the biotrophic phase are
      primarily associated with breakdown of the intercellular matrix and modification
      of the fungal mycelia, possibly to mask the fungus from plant defenses. Based on
      the transcriptome data, the upregulated secreted proteins in the necrotrophic
      phase are hypothesized to be actively attacking the plant cell walls and plant
      cellular components resulting in necrosis. These genes are being used to develop
      a new understanding of how this disease interaction progresses and to identify
      potential targets to reduce the impact of this devastating disease.

PMID- 24571093
TI  - Construction of a radiation hybrid panel and the first yellowtail (Seriola
      quinqueradiata) radiation hybrid map using a nanofluidic dynamic array.
AB  - BACKGROUND: Yellowtail (Seriola quinqueradiata) are an economically important
      species in Japan. However, there are currently no methods for captive breeding
      and early rearing for yellowtail. Thus, the commercial cultivation of this
      species is reliant upon the capture of wild immature fish. Given this, there is a
      need to develop captive breeding techniques to reduce pressure on wild stocks and
      facilitate the sustainable development of yellowtail aquaculture. We constructed
      a whole genome radiation hybrid (RH) panel for yellowtail gene mapping and
      developed a framework physical map using a nanofluidic dynamic array to use SNPs
      (single nucleotide polymorphisms) in ESTs (expressed sequence tags) for the DNA
      assisted breeding of yellowtail. RESULTS: Clonal RH cell lines were obtained
      after ionizing radiation; specifically, 78, 64, 129, 55, 42, and 53 clones were
      isolated after treatment with 3,000, 4,000, 5,000, 6,000, 8,000, or 10,000 rads,
      respectively. A total of 421 hybrid cell lines were obtained by fusion with mouse
      B78 cells. Ninety-four microsatellite markers used in the genetic linkage map
      were genotyped using the 421 hybrid cell lines. Based upon marker retention and
      genome coverage, we selected 93 hybrid cell lines to form an RH panel.
      Importantly, we performed the first genotyping of yellowtail markers in an RH
      panel using a nanofluidic dynamic array (Fluidigm, CA, USA). Then, 580 markers
      containing ESTs and SNPs were mapped in the first yellowtail RH map. CONCLUSIONS:
      We successfully developed a yellowtail RH panel to facilitate the localization of
      markers. Using this, a framework RH map was constructed with 580 markers. This
      high-density physical map will serve as a useful tool for the identification of
      genes related to important breeding traits using genetic structural information,
      such as conserved synteny. Moreover, in a comparison of 30 sequences in the RH
      group 1 (SQ1), yellowtail appeared to be evolutionarily closer to medaka and the
      green-spotted pufferfish than to zebrafish. We suggest that synteny analysis may
      be potentially useful as a tool to investigate chromosomal evolution by
      comparison with model fish.

PMID- 24571095
TI  - On phasic inhibition during hippocampal theta.
AB  - Two computational models are used to explore the possible implications of recent
      experimental data (Royer et al. 2012) on phasic inhibition during theta frequency
      (4-10 Hz) oscillations in the hippocampi of actively behaving rodents. A working
      hypothesis from previous experimental and modelling studies is that a theta cycle
      is divided into encoding (when synaptic plasticity is enhanced) and recall (when
      plasticity is suppressed) half cycles. Using a compartmental model of a CA1
      pyramidal cell, including dendritic spines, we demonstrate that out-of-phase
      perisomatic and dendritic inhibition, respectively, can promote the necessary
      conditions for these half cycles. Perisomatic inhibition allows dendritic calcium
      spikes that promote synaptic LTP, while minimising cell output. Dendritic
      inhibition, on the other hand, both controls cell output and suppresses dendritic
      calcium spikes, preventing LTP. The exact phase relationship between these sub
      cycles may not be fixed. Using a simple sum-of-sinusoids activity model, we
      suggest an interpretation of the data of Royer et al. (2012) in which a fixed
      phase encoding sub-cycle is surrounded by a flexible-phase recall cycle that
      follows the peak of excitatory drive and consequent phase precession of activity
      as an animal passes through a pyramidal cell's place field.

PMID- 24571096
TI  - Anxiolytic drugs and altered hippocampal theta rhythms: the quantitative systems
      pharmacological approach.
AB  - The spirit of systems pharmacology was adopted to study the possible mechanisms
      of anxiolytic drugs on hippocampal electric patterns. The frequency of the
      hippocampal theta rhythm increases linearly with the intensity of electrical
      stimulation to the brainstem. The reduction of mean theta frequency in this
      paradigm predicts the clinical efficacy of anxiolytic drugs. The purpose of this
      study was to investigate the mechanisms by which anxiolytics produce their
      characteristic effects on the slope and intercept of the stimulus-frequency
      relationship of hippocampal theta. A network of neuron populations that generates
      septo-hippocampal theta rhythm was modeled using a compartmental modeling
      technique. The influence of cellular and synaptic parameters on network frequency
      was studied. Results show that halving the rate of rise and fall of pyramidal
      hyperpolarization-activated (Ih) conductance lowers nPO elicited theta frequency
      at low levels of stimulation. Results also suggest that increasing the decay time
      constant of inhibitory post-synaptic current can reduce the frequency of low nPO
      stimulation elicited theta rhythm, while maximal synaptic conductance of GABA
      mediated synapses has little effect on frequency. Given their similar effect on
      network dynamics as by known anxiolytics, these parameter manipulations may mimic
      or predict the biophysical manifestations of anxiolytic action within the septo
      hippocampal system. 

PMID- 24571099
TI  - Perceptual grouping by entrainment in coupled Kuramoto oscillator networks.
AB  - In this article we present a network composed of coupled Kuramoto oscillators,
      which is able to solve a broad spectrum of perceptual grouping tasks. Based on
      attracting and repelling interactions between these oscillators, the network
      dynamics forms various phase-synchronized clusters of oscillators corresponding
      to individual groups of similar input features. The degree of similarity between
      features is determined by a set of underlying receptive fields, which are learned
      directly from the feature domain. After illustrating the theoretical principles
      of the network, the approach is evaluated in an image segmentation task.
      Furthermore, the influence of a varying degree of sparse couplings is evaluated. 

PMID- 24571097
TI  - Effect of heterogeneity and noise on cross frequency phase-phase and phase
      amplitude coupling.
AB  - Cross-frequency coupling is hypothesized to play a functional role in neural
      computation. We apply phase resetting theory to two types of cross-frequency
      coupling that can occur when a slower oscillator periodically forces one or more
      oscillators: phase-phase coupling, in which the two oscillations are phase
      locked, and phase-amplitude coupling, in which the amplitude of the driven
      oscillation is modulated. Our first result is that the shape of the phase
      resetting curve predicts the tightness of locking to a pulsatile forcing periodic
      input at any ratio of forced to intrinsic period; the tightness of the locking
      decreases as the ratio increases. Theoretical expressions were obtained for the
      probability density of the phases for a population of heterogeneous oscillators
      or a noisy single oscillator. Results were confirmed using two types of simulated
      networks and experiments on hippocampal CA1 neurons. Theoretical expressions were
      also obtained and confirmed for the probability density of N spike times within a
      single cycle of low frequency forcing. The second result is a suggested mechanism
      for phase-amplitude coupling in which progressive desynchronization leads to
      decreasing amplitude during a low frequency forcing cycle. Network simulations
      confirmed the theoretical viability of this mechanism, and that it generalizes to
      more diffuse input. 

PMID- 24571098
TI  - Gamma frequency feedback inhibition accounts for key aspects of orientation
      selectivity in V1.
AB  - There is now strong evidence that gamma frequency oscillations occur during the
      engagement of cortical regions. These oscillations involve gamma frequency
      feedback inhibition. Thus, understanding the properties of this form of
      inhibition is critical to understanding how excitation and inhibition interact to
      determine which cells fire and, more generally, how cortex performs computations.
      In previous work, we argued that gamma frequency inhibition performs a type of
      winner-take-all computation that obeys simple rules: 1) cells fire if their
      excitation is within E% of the cell with maximum excitation; 2) E%max is
      determined by the delay of feedback inhibition and the membrane time constant.
      This framework was previously applied to the best-studied cortical computation,
      orientation selectivity of cells in V1. Measurements show that orientation tuning
      is insensitive to illumination contrast. We showed that this finding can be
      simply explained by the E%max model. Recently, a new property of orientation
      selectivity has been discovered: orientation tuning varies with the phase of the
      gamma oscillation. Here, we show that this too can be simply explained by the
      E%max model. These successes suggest that simple rules underlie the selection of
      which cells fire in cortical networks. 

PMID- 24571100
TI  - Oscillations can reconcile slowly changing stimuli with short neuronal
      integration and STDP timescales.
AB  - Oscillatory brain activity has been widely reported experimentally, yet its
      functional roles, if any, are still under debate. In this review we argue two
      things: firstly, thanks to oscillations, even slowly changing stimuli can be
      encoded in precise relative spike times, decodable by downstream "coincidence
      detector" neurons in a feedforward manner. Secondly, the required connectivity to
      do so can spontaneously emerge with spike timing-dependent plasticity (STDP), in
      an unsupervised manner. The key here is that a common oscillatory drive enables
      neurons to remain under a fluctuation-driven regime. In this regime spike time
      jitter does not accumulate and can thus be lower than the intrinsic timescales of
      stimulus fluctuations, which leads to so-called "temporal encoding". Furthermore,
      the oscillatory drive formats the spikes in discrete oversampling volleys, and
      the relative spike times between neurons indicate the eventual differences in
      their activation levels. The oversampling accelerates the STDP-based learning for
      downstream neurons. After learning, readout only takes one oscillatory cycle.
      Finally, we also discuss experimental evidence, and the question of how the
      theory is complementary to the so-called "communication through coherence"
      theory. 

PMID- 24571102
TI  - HIV-negative gay men's accounts of using context-dependent sero-adaptive
      strategies.
AB  - We enrolled 166 gay and bisexual men who tested HIV-negative at a community
      sexual health clinic in Vancouver, British Columbia, into a year-long mixed
      methods study. A subsample of participants who reported recent condomless anal
      sex (n = 33) were purposively recruited into an embedded qualitative study and
      completed two in-depth qualitative interviews. Analysis of baseline interviews
      elicited three narratives relevant to men's use of context- or relationally
      dependent HIV-risk management strategies: (1) seroadaptive behaviours such as
      partner testing and negotiated safety agreements used with primary sexual
      partners, (2) serosorting and seroguessing when having sex with new partners and
      first-time hookups and (3) seroadaptive behaviours, including one or more of
      seropositioning/strategic positioning, condom serosorting and viral load sorting,
      used by participants who knowingly had sex with a serodiscordant partner. Within
      men's talk about sex, we found complex and frequently biomedically-informed
      rationale for seroadaptation in men's decisions to have what they understood to
      be various forms of safe or protected condomless anal sex. Our findings support
      the need for gay men's research and health promotion to meaningfully account for
      the multiple rationalities and seroadaptive strategies used for having condomless
      sex in order to be relevant to gay men's everyday sexual decision-making.

PMID- 24571101
TI  - The white-coat effect is an independent predictor of myocardial ischemia in
      resistant hypertension.
AB  - White-coat hypertension (WCH), commonly found in pseudoresistant hypertension,
      does not pose higher cardiovascular risk than hypertensive status. However, when
      the decrease of the out-of-office blood pressure does not reach normal levels -
      the white-coat effect (WCE) - the repercussions are still obscure. We
      investigated the repercussions of the WCE in myocardial perfusion in resistant
      hypertension (RHTN). We enrolled 129 asymptomatic RHTN subjects - divided into
      WCE (n = 63) and non-WCE (n = 66) - to perform rest and stress myocardial
      perfusion scintigraphy and biochemical tests. Groups were equal regarding age,
      gender and body mass index. There was a high prevalence of WCE (49%). WCE was
      associated with higher prevalence of myocardial ischemia (49.2% vs 7.6%, p <
      0.001), microalbuminuria (60.3% vs 36.4%, p = 0.01) and higher heart rate (72 [64
      80] vs 64 [60-69], p < 0.001), compared with non-WCE patients. On an adjusted
      logistic regression, heart rate was considered a predictor of WCE (OR = 1.10, 95%
      CI 1.04-1.15; p < 0.001), but not MA (OR = 1.8, 95% CI 0.8-3.9; p = 0.15). On a
      second model of adjusted logistic regression, WCE was an independent predictor of
      myocardial ischemia (OR = 14.7, 95% CI 4.8-44.8; p < 0.001). We found a high
      prevalence of WCE in RHTN, and this effect may predict silent myocardial ischemia
      in this subset of hypertensive patients. In this group of hypertensives special
      attention should be given to the WCE.

PMID- 24571103
TI  - An alternative synthetic approach for efficient catalytic conversion of syngas to
      ethanol.
AB  - Ethanol is an attractive end product and a versatile feedstock because a
      widespread market exists for its commercial use as a fuel additive or a potential
      substitute for gasoline. Currently, ethanol is produced primarily by fermentation
      of biomass-derived sugars, particularly those containing six carbons, but
      coproducts 5-carbon sugars and lignin remain unusable. Another major process for
      commercial production of ethanol is hydration of ethylene over solid acidic
      catalysts, yet not sustainable considering the depletion of fossil fuels.
      Catalytic conversion of synthetic gas (CO + H2) could produce ethanol in large
      quantities. However, the direct catalytic conversion of synthetic gas to ethanol
      remains challenging, and no commercial process exists as of today although the
      research has been ongoing for the past 90 years, since such the process suffers
      from low yield and poor selectivity due to slow kinetics of the initial C-C bond
      formation and fast chain growth of the C2 intermediates. This Account describes
      recent developments in an alternative approach for the synthesis of ethanol via
      synthetic gas. This process is an integrated technology consisting of the
      coupling of CO with methanol to form dimethyl oxalate and the subsequent
      hydrogenation to yield ethanol. The byproduct of the second step (methanol) can
      be separated and used in circulation as the feedstock for the coupling step. The
      coupling reaction of carbon monoxide for producing dimethyl oxalate takes place
      under moderate reaction conditions with high selectivity (~95%), which ideally
      leads to a self-closing, nonwaste, catalytic cycling process. This Account also
      summarizes the progress on the development of copper-based catalysts for the
      hydrogenation reaction with remarkable efficiencies and stability. The unique
      lamellar structure and the cooperative effect between surface Cu(0) and Cu(+)
      species are responsible for the activity of the catalyst with high yield of
      ethanol (~91%). The understanding of nature of valence states of Cu could also
      guide the rational design of Cu-based catalysts for other similar reactions,
      particularly for hydrogenation catalytic systems. In addition, by regulating the
      reaction condition and the surface structure of the catalysts, the products in
      the hydrogenation steps, such as ethanol, methyl glycolate, and ethylene glycol,
      could be tuned efficiently. This synthetic approach enables a more sustainable
      ethanol, methyl glycolate, and ethylene glycol synthesis in industry and greatly
      reduces the dependence on petroleum resources and the emission of the greenhouse
      gas.

PMID- 24571104
TI  - Hydrogen bond dynamics in intrinsically disordered proteins.
AB  - Hydrogen bond dynamics is used to investigate the internal motions and structural
      plasticity of intrinsically disordered (ID) proteins. Group a represent
      completely disordered proteins, while group b proteins are comprised of regular
      secondary structures linked by flexible disordered regions. Molecular dynamics
      simulations of two different groups of ID proteins provide an insight into the
      hydrogen bond dynamics via the evaluation of the continuous and intermittent time
      autocorrelation functions. The intermolecular hydrogen bonds between the residues
      of the ID proteins and water record a short lifetime in both groups of proteins.
      The intermolecular hydrogen bonds relax faster at a constant rate compared to
      that of the intramolecular hydrogen bonds whose rate of decay fluctuate during
      the entire simulation trajectory. The simulations reveal that the intramolecular
      hydrogen bonds have a longer lifetime in group b proteins compared to those in
      group a proteins. The hydrophilic residues in ID proteins form stable persistent
      intramolecular hydrogen bonds as compared to the hydrophobic residues and help to
      maintain the dynamic equilibrium among the interconvertible conformations. 

PMID- 24571105
TI  - Atypical hereditary spastic paraplegia mimicking multiple sclerosis associated
      with a novel SPG11 mutation.

PMID- 24571106
TI  - Susceptibility-weighted imaging changes suggesting brain iron accumulation in
      Huntington's disease: an epiphenomenon which causes diagnostic difficulty.

PMID- 24571108
TI  - Synergy of different fluorescent enhancement effects on spiropyran appended onto
      cellulose.
AB  - An excellent fluorescent material derived from spiropyran species was facilely
      fabricated by appending spiropyran onto the cellulose matrix via a covalent link
      of an ester carbonyl group. The interior high-polar environment in the porous
      cellulose matrix can promote the concentration of the merocyanine form; the
      conformational constraint of cellulose cavities and the elimination of solvent
      influence can sufficiently develop the quantum yield of merocyanine. In contrast
      with other spiropyran materials, the synergy of the three different effects can
      significantly enhance the fluorescent intensity of the spiropyran compound by 1
      order of magnitude approximately. These experimental results may bring about more
      promising applications of spiropyran species beyond their photochromic
      properties. 

PMID- 24571109
TI  - Introduction.

PMID- 24571110
TI  - The history of the concept of epileptic encephalopathy.
AB  - The first description of epileptic encephalopathies dates back to Dr. West who,
      in 1857, described the syndrome that took his name. In addition to West syndrome,
      in the last century other epileptic syndromes entered into the chapter of
      epileptic encephalopathies. Henry Gastaut has the virtue of having created the
      modern concept of epileptic encephalopathy and entering it into the official
      terminology of the International League Against Epilepsy (ILAE). After the first
      proposal, it was further defined and refined over time. 

PMID- 24571112
TI  - Do seizures and epileptic activity worsen epilepsy and deteriorate cognitive
      function?
AB  - Relevant to the definition of epileptic encephalopathy (EE) is the concept that
      the epileptic activity itself may contribute to bad outcomes, both in terms of
      epilepsy and cognition, above and beyond what might be expected from the
      underlying pathology alone, and that these can worsen over time. The review of
      the clinical and experimental evidence that seizures or interictal
      electroencephalography (EEG) discharges themselves can induce a progression
      toward more severe epilepsy and a regression of brain function leads to the
      following conclusions: The possibility of seizure-dependent worsening is by no
      means a general one but is limited to some types of epilepsy, namely mesial
      temporal lobe epilepsy (MTLE) and EEs. Clinical and experimental data concur in
      indicating that prolonged seizures/status epilepticus (SE) are a risky initial
      event that can set in motion an epileptogenic process leading to persistent,
      possibly drug-refractory epilepsies. The mechanisms for SE-related epileptogenic
      process are incompletely known; they seem to involve inflammation and/or
      glutamatergic transmission. The evidence of the role of recurrent individual
      seizures in sustaining epilepsy progression is ambiguous. The correlation between
      high seizure frequency and bad outcome does not necessarily demonstrate a cause
      effect relationship, rather high seizure frequency and bad outcome can both
      depend on a particularly aggressive epileptogenic process. The results of EE
      studies challenge the idea of a common seizure-dependent mechanism for epilepsy
      progression/intellectual deterioration. 

PMID- 24571113
TI  - Genetic epileptic encephalopathies: is all written into the DNA?
AB  - Epileptic encephalopathy is a condition in which epileptic activity, clinical or
      subclinical, is thought to be responsible for any disturbance of cognition,
      behavior, or motor control. However, experimental evidence supporting this
      clinical observation are still poor and the causal relationship between
      pharmacoresistant seizures and cognitive outcome is controversial. In the past
      two decades, genetic studies shed new light onto complex mechanisms underlying
      different severe epileptic conditions associated with intellectual disability and
      behavioral abnormalities, thereby providing important clues on the relationship
      between seizures and cognitive outcome. Dravet syndrome is a childhood disorder
      associated with loss-of-function mutations in SCN1A and is characterized by
      frequent seizures and severe cognitive impairment, thus well illustrating the
      concept of epileptic encephalopathy. However, it is difficult to determine the
      causative role of the underlying sodium channel dysfunction and that of the
      consequent seizures in influencing cognitive outcome in these children. It is
      also difficult to demonstrate whether a recognizable profile of cognitive
      impairment or a definite behavioral phenotype exists. Data from the laboratory
      and the clinics may provide greater insight into the degree to which epileptic
      activity may contribute to cognitive impairment in individual syndromes. 

PMID- 24571111
TI  - Pathophysiology of epileptic encephalopathies.
AB  - The application of metabolic imaging and genetic analysis, and now the
      development of appropriate animal models, has generated critical insights into
      the pathogenesis of epileptic encephalopathies. In this article we present ideas
      intended to move from the lesions associated with epileptic encephalopathies
      toward understanding the effects of these lesions on the functioning of the
      brain, specifically of the cortex. We argue that the effects of focal lesions may
      be magnified through the interaction between cortical and subcortical structures,
      and that disruption of subcortical arousal centers that regulate cortex early in
      life may lead to alterations of intracortical synapses that affect a critical
      period of cognitive development. Impairment of interneuronal function globally
      through the action of a genetic lesion similarly causes widespread cortical
      dysfunction manifesting as increased delta slow waves on electroencephalography
      (EEG) and as developmental delay or arrest clinically. Finally, prolonged focal
      epileptic activity during sleep (as occurring in the syndrome of continuous spike
      wave in slow sleep, or CSWSS) might interfere with local slow wave activity at
      the site of the epileptic focus, thereby impairing the neural processes and,
      possibly, the local plastic changes associated with learning and other cognitive
      functions. Seizures may certainly add to these pathologic processes, but they are
      likely not necessary for the development of the cognitive pathology.
      Nevertheless, although seizures may be either a consequence or symptom of the
      underlying lesion, their effective treatment can improve outcomes as both
      clinical and experimental studies may suggest. Understanding their substrates may
      lead to novel, effective treatments for all aspects of the epileptic
      encephalopathy phenotype. 

PMID- 24571114
TI  - Functional neuroimaging in epileptic encephalopathies.
AB  - Epileptic encephalopathies (EEs) represent a group of severe epileptic disorders
      associated with cognitive and behavioral disturbances. The mechanisms of
      cognitive disability in EEs remain unclear. This review summarized neuroimaging
      studies that have tried to describe specific fingerprints of brain activation in
      EE. Although the epileptic activity can be generated individually in different
      brain regions, it seems likely that the activity propagates in a syndrome
      specific way. In some EEs, the epileptiform discharges were associated with an
      interruption of activity in the default mode network. In another EE, other
      mechanisms seem to underlie cognitive disability associated with epileptic
      activity, for example, abnormal connectivity pattern or interfering activity in
      the thalamocortical network. Further neuroimaging studies are needed to
      investigate the short-term and long-term impact of epileptic activity on
      cognition and development. 

PMID- 24571115
TI  - Epileptic encephalopathy as models of system epilepsy.
AB  - The pathophysiology of epileptic encephalopathies has long been debated.
      Recently, some authors proposed the new concept of so-called system epilepsies.
      This hypothesis postulates that system epilepsies are produced by the enduring
      propensity to generate seizures in different cerebral areas that, alone, are
      unable to create a specific electroclinical phenotype. This goes beyond the
      classical dichotomy between focal and generalized epilepsy. Epileptic
      encephalopathies, in general, have the ideal profile to be considered as system
      epilepsies, and West syndrome and Lennox-Gastaut syndrome are two of the best
      examples. Apart from the conventional neurophysiologic methods for studying brain
      activities and the pathophysiologic mechanisms underlying epileptic syndromes,
      other new methods of neuroimaging support this hypothesis. 

PMID- 24571116
TI  - Neuropsychological approaches to epileptic encephalopathies.
AB  - The International League Against Epilepsy (ILAE) Commission report on
      classification and terminology indicates that "diagnosing an individual as having
      an encephalopathic course requires demonstration of a failure to develop as
      expected relative to the same-aged peers or to regress in abilities." In this
      chapter, basing our discussion on the theoretical framework of
      neuroconstructivism, on the latest results deriving from functional neuroimaging
      and on the concept of system epilepsy, we use continuous spike-waves during slow
      wave sleep (CSWS) as an example of how non-rapid eye movement (NREM) sleep spikes
      interfere with the organization and consolidation of neuropsychological networks
      in the sensitive phase of development, affecting also interconnected systems.
      Indeed, recent discoveries show that the normal overnight downscaling of slow
      wave activity (SWA) from the first to the last hours of sleep is absent in
      electrical status epilepticus during sleep (ESES) patients, thus impairing the
      neural process and possibly the local plastic changes associated with learning
      and other cognitive functions. Moreover, specific patterns of spike-induced
      activation (especially in perisylvian and/or prefrontal areas) and deactivation
      of default mode network (DMN) have been shown in patients with CSWS.
      Consequently, to date, we may conceive that the possible mechanisms underlying
      neuropsychological disorders in encephalopathic epilepsy (EE) may be double,
      since NREM sleep interictal epileptic discharges (IEDs) induce both a pathologic
      activation in epileptogenic areas and a pathologic deactivation of DMN beyond the
      epileptogenic zone. The growing body of literature on the effects of ESES in CSWS
      provides us with increasing knowledge on the complexity of brain development and
      a better understanding of plasticity, enlightening the pathogenesis of damage on
      developing neuropsychological functions. Finally, the need for an individually
      tailored interpretation of the neuropsychological testing results, expected to
      integrate neurophysiology and functional neuroimaging data, is suggested. 

PMID- 24571118
TI  - NKX2-5, SIL/TAL and TLX3/HOX11L2 expression in Egyptian pediatric T-cell acute
      lymphoblastic leukemia.
AB  - AIM: Cohorts of T-cell acute lymphoblastic leukemia (T-ALL) patients show
      regional geographic differences in incidence, biological features and clinical
      outcome, implying that in different populations, cases may harbor different
      genetic lesions than those reported elsewhere. In this study, we prospectively
      evaluated the frequency and the clinical relevance of NKX2-5, TLX3/HOX11L2 and
      SIL/TAL expression in Egyptian childhood T-ALL. METHODS: NKX2-5, TLX3/HOX11L2 and
      SIL/TAL expression were tested in peripheral blood and/or bone marrow of 83 newly
      diagnosed Egyptian childhood T-ALL patients. RESULTS: NKX2-5 expression was
      detected in 11/83 cases (13%), TLX3/HOX11L2 (5/83, 6%) and SIL/TAL (4/83, 5%).
      Initial central nervous system involvement was significantly higher in the NKX2-5
      positive versus negative patients (P = 0.009). The follow-up period was a median
      of 65.5 months. The 5-year leukemia-free and event-free survival rates of the
      whole T-ALL population were 70 +/- 6% and 58 +/- 6%, respectively. The 5-year
      leukemia-free and event-free survival rates of NKX2-5 were 86 +/- 13% and 60 +/-
      16%, respectively. There were no statistically significant differences in
      clinical presentation, biological features, initial response to chemotherapy, or
      subsequent treatments between the subgroups and the total population. CONCLUSION:
      Egyptian T-ALL cases seemed to have a different genetic pattern compared to other
      populations, with a lower incidence of TLX3/HOX11L2 and SIL/TAL but a higher
      incidence of NKX2-5 expression than recorded in Western countries.

PMID- 24571117
TI  - Therapeutic approach to epileptic encephalopathies.
AB  - Epileptic encephalopathies (EEs) are electroclinical entities with a peculiar
      course of disease; seizures and electroencephalographic (EEG) epileptiform
      abnormalities, ictal and interictal, contribute to progressive disturbance of
      cerebral functions. Frequently EEs are drug resistant, and consequences may be
      catastrophic. The main goal of treatment is to stop the peculiar course of
      epilepsy, operating on three parameters: seizure control, reduction of EEG
      abnormalities, and developmental outcome. For a correct therapeutic approach it
      is mandatory to have an as accurate as possible syndromic and etiologic
      diagnosis. Given the poor efficacy of conventional antiepileptic drugs (AEDs),
      the use of specific drugs for EEs, such as adrenocorticotropic hormone (ACTH) and
      corticosteroids or stiripentol is suggested. In some cases the choice of
      treatment is strictly related to the etiology: vigabatrin in tuberous sclerosis,
      ketogenic diet in glucose transporter type 1 (GLUT-1) deficiency, and pyridoxine
      in pyridoxine deficiency. Some AEDs combinations, such as sodium valproate with
      lamotrigine, have also provided interesting results, for example, in Lennox
      Gastaut syndrome, although controlled studies are lacking. Finally, early surgery
      can be an option in children with focal structural abnormalities responsible for
      EEs preferably before irreversible damage on developmental outcome.
      Multispecialist support is recommended in EE. Management should be global from
      the onset, integrating not only seizure control but also all issues related to
      comorbidities, particularly neuropsychological and psychiatric. 

PMID- 24571119
TI  - Efficacy of prophylactic intra-aortic balloon pump therapy in chronic heart
      failure patients undergoing cardiac surgery.
AB  - This study investigated the efficacy of prophylactic intraoperative intra-aortic
      balloon pump (IABP) usage in chronic heart failure patients with severely reduced
      left ventricular function undergoing elective cardiac surgery. Between January
      2008 and December 2012, 107 patients with severely reduced left ventricular
      ejection fraction (LVEF <35%) received prophylactic intraoperative IABP
      implantation during open-heart surgery. Surgical procedures performed were
      isolated coronary artery bypass grafting (CABG) in 35 patients (32.7%), aortic
      valve replacement in 12 (11.2%), mitral valve repair or replacement in 15
      (14.0%), combined valve and CABG procedures in 27 (25.2%), and other surgical
      procedures in 18 (16.8%). Results and outcomes were compared with those in a
      propensity score-matched cohort of 107 patients who underwent cardiac surgery
      without intraoperative IABP implantation. Matching criteria were age, gender,
      LVEF, and surgical procedure. Duration of intensive care unit (ICU) stay,
      duration of hospital stay, and 30-day mortality were markers of outcome. In the
      IABP group, mean patient age was 69.1 +/- 13.7 years; 66.4% (70) were male. All
      IABPs were placed intraoperatively. Mean duration of IABP application time was
      42.4 +/- 8.7 h. IABP-related complications occurred in five patients (4.7%),
      including one case of inguinal bleeding, one case of mesenteric ischemia, and
      ischemia of the lower limb in three patients. No stroke or major bleeding
      occurred during IABP support. Mean durations of ICU and hospital stay were 3.38
      +/- 2.15 days and 7.69 +/- 2.02 days, respectively, in the IABP group, and 4.20
      +/- 3.14 days and 8.57 +/- 3.26 days in the control group, showing statistically
      significant reductions in duration of ICU and hospital stay in the IABP group
      (ICU stay, P = 0.036; hospital stay, P = 0.015). Thirty-day survival rates were
      92.5 and 94.4% in the IABP and control group, respectively, showing no
      statistically significant difference (P = 0.75). IABP usage in chronic heart
      failure patients with severely reduced LVEF undergoing cardiac surgery was safe
      and resulted in shorter ICU and hospital stay but did not influence 7- and 30-day
      survival rates.

PMID- 24571120
TI  - The DSM-5 classification of mood disorders: some fallacies and fault lines.

PMID- 24571121
TI  - Resting-state functional magnetic resonance imaging: the impact of regression
      analysis.
AB  - PURPOSE: To investigate the impact of regression methods on resting-state
      functional magnetic resonance imaging (rsfMRI). During rsfMRI preprocessing,
      regression analysis is considered effective for reducing the interference of
      physiological noise on the signal time course. However, it is unclear whether the
      regression method benefits rsfMRI analysis. MATERIALS AND METHODS: Twenty
      volunteers (10 men and 10 women; aged 23.4 +/- 1.5 years) participated in the
      experiments. We used node analysis and functional connectivity mapping to assess
      the brain default mode network by using five combinations of regression methods.
      RESULTS: The results show that regressing the global mean plays a major role in
      the preprocessing steps. When a global regression method is applied, the values
      of functional connectivity are significantly lower (P <= .01) than those
      calculated without a global regression. This step increases inter-subject
      variation and produces anticorrelated brain areas. CONCLUSION: rsfMRI data
      processed using regression should be interpreted carefully. The significance of
      the anticorrelated brain areas produced by global signal removal is unclear.

PMID- 24571122
TI  - Impact of noncancer pain on health-related quality of life.
AB  - BACKGROUND: While the economic costs of pain have been documented, the impact of
      noncancer pain on quality of life has not been studied extensively. OBJECTIVE: To
      estimate the influence of noncancer pain on quality of life measures. DESIGN:
      Prospective, multicenter, observational nonrandomized patient pain registry.
      SETTING: Outpatient settings. PARTICIPANTS: Patients with acute episodes of
      noncancer pain requiring treatment with a prescription medication containing
      oxycodone immediate-release on an as-needed basis for at least 5 days (n = 629).
      MEASUREMENTS: The modified Brief Pain Inventory and the 12-item Short Form Health
      Survey (SF-12) was measured at baseline when oxycodone immediate-release began
      and days 7, 14, 21, and 28. Repeated measures mixed models provided estimates of
      impact of pain on the physical component summary score (PCS) and mental health
      component summary score (MCS) of the SF-12. RESULTS: Patterns indicating pain
      oscillation over the 28-day window were common (Range: 44.3% back/neck pain
      cohort to 61.2% postoperative cohort). After adjustment for sociodemographics,
      concomitant medications and gastrointestinal symptoms, worst pain in 24 hours was
      associated with a 13.9 point PCS reduction (adjusted PCS for pain = 10: 31.1;
      adjusted PCS for pain = 0: 45.0) and a 7.2 point MCS reduction (adjusted MCS for
      pain = 10: 44.1; adjusted MCS for pain = 0: 51.3). Similar clinically relevant
      differences were observed among patients with arthritis, back/neck pain,
      injury/trauma, postoperative pain, neuropathic pain and fibromyalgia, although
      statistical significance was not observed in the latter 2 groups. CONCLUSION:
      Among outpatients with various underlying causes of pain, the negative impact of
      pain on physical and mental health-related quality of life is significant.

PMID- 24571123
TI  - Adolescent girls with emotional disorders have a lower end-tidal CO2 and
      increased respiratory rate compared with healthy controls.
AB  - Hyperventilation has been linked to emotional distress in adults. This study
      investigates end-tidal carbon dioxide (ETCO2 ), respiratory rate (RR), and heart
      rate variability (HRV) in adolescent girls with emotional disorders and healthy
      controls. ETCO2 , RR, HRV, and ratings of emotional symptom severity were
      collected in adolescent female psychiatric patients with emotional disorders (n =
      63) and healthy controls (n = 62). ETCO2 and RR differed significantly between
      patients and controls. ETCO2, HR, and HRV were significant independent predictors
      of group status, that is, clinical or healthy, while RR was not. ETCO2 and RR
      were significantly related to emotional symptom severity and to HRV in the total
      group. ETCO2 and RR were not affected by use of selective serotonin reuptake
      inhibitors. It is concluded that emotional dysregulation is related to
      hyperventilation in adolescent girls. Respiratory-based treatments may be
      relevant to investigate in future research.

PMID- 24571125
TI  - Preparation of a protected 3-deoxy-D-manno-oct-2-ulosonate glycal donor for the
      synthesis of beta-KDO-containing oligosaccharides.
AB  - A practical method for the synthesis of KDO glycal donors was developed. The
      prepared KDO donors exhibited excellent disastereoselectivity of glycosylation in
      a CH2Cl2-CH3CN solvent mixture, which was found to be associated with the
      isopropylidene protection at the C-4 and C-5 hydroxyls. The synthetic use of the
      KDO donor was demonstrated in the preparation of beta-KDO-containing
      oligosaccharides.

PMID- 24571124
TI  - The role of platelets in coagulation dysfunction in xenotransplantation, and
      therapeutic options.
AB  - Xenotransplantation could resolve the increasing discrepancy between the
      availability of deceased human donor organs and the demand for transplantation.
      Most advances in this field have resulted from the introduction of genetically
      engineered pigs, e.g., alpha1,3-galactosyltransferase gene-knockout (GTKO) pigs
      transgenic for one or more human complement-regulatory proteins (e.g., CD55,
      CD46, CD59). Failure of these grafts has not been associated with the classical
      features of acute humoral xenograft rejection, but with the development of
      thrombotic microangiopathy in the graft and/or consumptive coagulopathy in the
      recipient. Although the precise mechanisms of coagulation dysregulation remain
      unclear, molecular incompatibilities between primate coagulation factors and pig
      natural anticoagulants exacerbate the thrombotic state within the xenograft
      vasculature. Platelets play a crucial role in thrombosis and contribute to the
      coagulation disorder in xenotransplantation. They are therefore important targets
      if this barrier is to be overcome. Further genetic manipulation of the organ
      source pigs, such as pigs that express one or more coagulation-regulatory genes
      (e.g., thrombomodulin, endothelial protein C receptor, tissue factor pathway
      inhibitor, CD39), is anticipated to inhibit platelet activation and the
      generation of thrombus. In addition, adjunctive pharmacologic anti-platelet
      therapy may be required. The genetic manipulations that are currently being
      tested are reviewed, as are the potential pharmacologic agents that may prove
      beneficial. 

PMID- 24571126
TI  - Investigational new insulin glargine 300 U/ml has the same metabolism as insulin
      glargine 100 U/ml.
AB  - Insulin glargine is processed in vivo into soluble 21(A) -Gly-human insulin (M1),
      the principal moiety responsible for metabolic effects, and subsequently into M2.
      This sub-study compared metabolism and metabolite pharmacokinetic (PK) profiles
      of investigational new insulin glargine U300 (Gla-300) with insulin glargine 100
      U/ml (Gla-100, Lantus(r), Sanofi-Aventis Deutschland GmbH, Frankfurt am Main,
      Germany) in people with type 1 diabetes. Participants received 0.4 (n = 18) or
      0.6 U/kg Gla-300 (n = 12), and 0.4 U/kg Gla-100 (n = 30) once daily in randomized
      order for 8 days prior to a 36-h euglycaemic clamp. Metabolites were quantified
      using immunoaffinity enrichment and liquid chromatography tandem mass
      spectrometry (LC-MS/MS). Glargine metabolism was the same regardless of Gla-100
      or Gla-300 administration; M1 was confirmed as the principal active moiety
      circulating in blood. Steady state concentrations of M1 were achieved after 2
      days for Gla-100, and 4 days for Gla-300. Steady state M1 values defined
      prolonged and even flatter PK profiles after Gla-300 administration compared with
      M1 profiles after Gla-100.

PMID- 24571127
TI  - A novel HLA-A allele, HLA-A*02:441, identified by sequence-based typing in
      Chinese individuals.
AB  - HLA-A*02:441 differs from HLA-A*02:01:01:01 by one nucleotide exchange at
      position 91(T>C) with an amino acid exchange. 

PMID- 24571131
TI  - Rate coefficients for the gas-phase reaction of chlorine atoms with a series of
      methoxylated aromatic compounds.
AB  - The reaction of a series of oxygenated aromatics (two methoxybenzene and six
      methoxyphenol isomers) with chlorine atoms has been studied in two simulation
      chambers with volumes of 1080 and 480 L at the University of Wuppertal.
      Experiments were performed at 295 +/- 2 K and a total pressure of synthetic air
      of 1 bar using the relative kinetic method with in situ Fourier transform
      infrared spectroscopy for chemical analysis. The following rate coefficients (in
      units of cubic centimeter per molecule per second) were determined: (1.07 +/-
      0.24) * 10(-10) for methoxybenzene, (1.20 +/- 0.24) * 10(-10) for 1-methoxy-2
      methylbenzene, (2.97 +/- 0.66) * 10(-10) for 2-methoxyphenol (guaiacol), (2.99 +/
      0.62) * 10(-10) for 3-methoxyphenol, (2.86 +/- 0.58) * 10(-10) for 4
      methoxyphenol, (3.35 +/- 0.68) * 10(-10) for 2-methoxy-4-methylphenol, (4.73 +/-
      1.06) * 10(-10) for 2,3-dimethoxyphenol, and (2.71 +/- 0.61) * 10(-10) for 2,6
      dimethoxyphenol (syringol). To the best of our knowledge, this work represents
      the first determination of the rate coefficients for the gas-phase reaction of
      the chlorine atoms with the methoxy-aromatic compounds investigated. The
      reactivity of the methoxylated aromatics toward Cl is compared with that of other
      substituted aromatic compounds, and the differences in the rate coefficients are
      interpreted in terms of the type, number, and position of the different
      substituents on the aromatic ring. The atmospheric implications of the studied
      reactions are also discussed. 

PMID- 24571130
TI  - Ellagic acid induces novel and atypical PKC isoforms and promotes caspase-3
      dependent apoptosis by blocking energy metabolism.
AB  - Antioxidant ellagic acid is a herbal polyphenolic compound shown to possess
      growth-inhibiting and apoptotic activities in cancer. Protein kinase C (PKC)
      plays an important role in cell proliferation, apoptosis, and differentiation.
      Apoptosis of tumor cells is induced by inactivation of glycolytic enzyme of
      anaerobic metabolism, lactate dehydrogenase (LDH)-A, and by activating apoptotic
      protein caspase-3 via PKCdelta. The present study aims to analyze the role of
      ellagic acid on regulation of novel and atypical isozymes of PKC to modulate
      apoptosis and anaerobic metabolism to prevent lymphoma growth as its role on
      classical PKCs is reported earlier. Expression of novel and atypical isozymes of
      PKC, activity of PKCdelta, expression and activity of caspase-3, and LDH-A have
      been analyzed. Expression is measured by RT-PCR, activities of PKCdelta as level
      of its catalytic fragment, caspase-3 as level of its p17 fragment, and LDH-A by
      specific staining. Lymphoma bearing mice were treated with 3 different doses of
      ellagic acid. The treatment enhanced expression of all novel and atypical PKCs,
      activity and expression of caspase-3, and activity of PKCdelta but decreased
      activity and expression of LDH-A. Our results suggest that ellagic acid induces
      apoptosis via novel and atypical PKCs in association with caspase-3 and induces
      cancer cell death by blocking the energy metabolism. 

PMID- 24571129
TI  - Stratified doubly robust estimators for the average causal effect.
AB  - Suppose we are interested in estimating the average causal effect from an
      observational study. A doubly robust estimator, which is a hybrid of the outcome
      regression and propensity score weighting, is more robust than estimators
      obtained by either of them in the sense that, if at least one of the two models
      holds, the doubly robust estimator is consistent. However, a doubly robust
      estimator may still suffer from model misspecification since it is not consistent
      if neither of them is correctly specified. In this article, we propose an
      alternative estimator, called the stratified doubly robust estimator, by further
      combining propensity score stratification with outcome regression and propensity
      score weighting. This estimator allows two candidate models for the propensity
      score and is more robust than existing doubly robust estimators in the sense that
      it is consistent either if the outcome regression holds or if one of the two
      models for the propensity score holds. Asymptotic properties are examined and
      finite sample performance of the proposed estimator is investigated by simulation
      studies. Our proposed method is illustrated with the Tone study, which is a
      community survey conducted in Japan.

PMID- 24571128
TI  - Mapping structurally defined guanine oxidation products along DNA duplexes:
      influence of local sequence context and endogenous cytosine methylation.
AB  - DNA oxidation by reactive oxygen species is nonrandom, potentially leading to
      accumulation of nucleobase damage and mutations at specific sites within the
      genome. We now present the first quantitative data for sequence-dependent
      formation of structurally defined oxidative nucleobase adducts along p53 gene
      derived DNA duplexes using a novel isotope labeling-based approach. Our results
      reveal that local nucleobase sequence context differentially alters the yields of
      2,2,4-triamino-2H-oxal-5-one (Z) and 8-oxo-7,8-dihydro-2'-deoxyguanosine (OG) in
      double stranded DNA. While both lesions are overproduced within endogenously
      methylated (Me)CG dinucleotides and at 5' Gs in runs of several guanines, the
      formation of Z (but not OG) is strongly preferred at solvent-exposed guanine
      nucleobases at duplex ends. Targeted oxidation of (Me)CG sequences may be caused
      by a lowered ionization potential of guanine bases paired with (Me)C and the
      preferential intercalation of riboflavin photosensitizer adjacent to (Me)C:G base
      pairs. Importantly, some of the most frequently oxidized positions coincide with
      the known p53 lung cancer mutational "hotspots" at codons 245 (GGC), 248 (CGG),
      and 158 (CGC) respectively, supporting a possible role of oxidative degradation
      of DNA in the initiation of lung cancer. 

PMID- 24571132
TI  - Genome sequencing reveals the environmental origin of enterococci and potential
      biomarkers for water quality monitoring.
AB  - Enterococci are common members of the gut microbiome and their ease of culturing
      has facilitated worldwide use as indicators of fecal pollution of waters.
      However, enterococci were recently shown to persist in environmental habitats,
      often in the absence of fecal input, potentially confounding water quality
      assays. Toward resolving this issue and providing a more complete picture of
      natural enterococci diversity, 11 isolates of Enterococcus faecalis recovered
      from freshwater watersheds (environmental) were sequenced and compared to 59
      available enteric genomes. Phenotypically and phylogenetically the environmental
      E. faecalis were indistinguishable from their enteric counterparts. However,
      distinct environmental- and enteric-associated gene signatures, encoding mostly
      accessory nutrient utilization pathways, were detected among the variable genes.
      Specifically, a nickel uptake operon was over-represented in environmental
      genomes, while genes for utilization of sugars thought to be abundant in the gut
      such as xylose were over-represented in enteric genomes. The distribution and
      phylogeny of these identified signatures suggest that ancestors of E. faecalis
      resided in extra-enteric habitats, challenging the prevailing commensal view of
      enterococci ecology. Thus, habitat-associated gene content changes faster than
      core genome phylogeny and may include biomarkers for reliably detecting fecal
      contaminants for improved microbial water quality monitoring. 

PMID- 24571133
TI  - Removal of biofilms by intermittent low-intensity ultrasonication triggered
      bursting of microbubbles.
AB  - In this study, a chemical-free cleaning method for biofilms removal is presented,
      which is based on intermittent low-intensity ultrasonication (US) triggered
      bursting of microbubbles (MB) in such a sequence that MB were continuously
      introduced into the reaction vessel for 15 min, while US was activated for 2 s
      after every 2 min of microbubbling. It was found that the fixed biomass, and the
      extracellular proteins and polysaccharides of 24-h old biofilms grown on a nylon
      membrane surface were reduced, respectively, by 75, 79 and 72% after treatment by
      the US + MB method. Fourier transform infrared (FTIR) analysis further revealed
      that the chemical composition of the biofilms was not altered by the US + MB
      treatment, suggesting that biofilms were removed through physical forces due to
      the generation of a shock wave and a high-speed water jet through US-triggered
      bursting of the MB. The proposed method can be considered a chemical-free
      technology for biofilm removal. 

PMID- 24571135
TI  - Oregon patients with HIV infection who experience delayed diagnosis.
AB  - This project sought to understand factors contributing to the delayed diagnosis
      of HIV in the state of Oregon, USA in order to increase timely testing and
      diagnosis. People unaware of their positive HIV status account for a
      disproportionate number of transmissions of HIV, making delayed diagnosis a
      profound public health concern. We interviewed a sample of 17 adults, diverse in
      age, reported risk behaviors and sexual orientation, who were identified as being
      diagnosed late, about their experiences with testing and diagnosis. We defined
      delayed diagnosis as a diagnosis of AIDS within 12 months of the first positive
      HIV test. We conducted thematic analysis using NVivo(r) software for data
      management. Three overarching themes emerged: risk perception, missed
      opportunities for diagnosis, routine testing and the role of the medical
      community. Definitions of these themes, corresponding sub-themes, and illustrious
      quotations provide an informative description of characteristics of late testers,
      factors contributing to delayed diagnosis, and potential points of intervention
      to increase regular and timely testing. We conclude that routine HIV screening as
      part of regular medical care might significantly reduce the number of delayed
      diagnoses and minimize the stigma of testing by normalizing it as part of routine
      medical care. Earlier diagnosis of HIV will result in better outcomes for
      individual patients and lower rates of HIV transmission by unknowing individuals.

PMID- 24571136
TI  - Synergy between polyamine and anionic surfactant: a bioinspired approach for
      ordered mesoporous silica.
AB  - A novel bioinspired approach for ordered mesoporous silica was developed on the
      basis of the synergic coassembly between polyamine and an anionic surfactant as a
      template. With the help of cationic polyamine, anionic surfactant micelles could
      be utilized as a mesostructure template, whereas with the aid of the anionic
      surfactant micelles the cationic polyamine chains underwent aggregation to exert
      their ability to induce silica condensation. Mesoporous silicas with well-ordered
      mesostructure of Fd-3m symmetry and 3D hexagonal close-packed mesostructure (hcp)
      were fabricated. Because of the abundant types of anionic surfactants and
      polyamines, the synthesis approach can be regarded as a general method for
      anionic-surfactant-templated mesoporous silica, and new mesostructures and
      morphologies are expected. 

PMID- 24571134
TI  - Atomic force microscopy probing of receptor-nanoparticle interactions for
      riboflavin receptor targeted gold-dendrimer nanocomposites.
AB  - Riboflavin receptors are overexpressed in malignant cells from certain human
      breast and prostate cancers, and they constitute a group of potential surface
      markers important for cancer targeted delivery of therapeutic agents and imaging
      molecules. Here we report on the fabrication and atomic force microscopy (AFM)
      characterization of a core-shell nanocomposite consisting of a gold nanoparticle
      (AuNP) coated with riboflavin receptor-targeting poly(amido amine) dendrimer. We
      designed this nanocomposite for potential applications such as a cancer targeted
      imaging material based on its surface plasmon resonance properties conferred by
      AuNP. We employed AFM as a technique for probing the binding interaction between
      the nanocomposite and riboflavin binding protein (RfBP) in solution. AFM enabled
      precise measurement of the AuNP height distribution before (13.5 nm) and after
      chemisorption of riboflavin-conjugated dendrimer (AuNP-dendrimer; 20.5 nm).
      Binding of RfBP to the AuNP-dendrimer caused a height increase to 26.7 nm, which
      decreased to 22.8 nm when coincubated with riboflavin as a competitive ligand,
      supporting interaction of AuNP-dendrimer and its target protein. In summary,
      physical determination of size distribution by AFM imaging can serve as a
      quantitative approach to monitor and characterize the nanoscale interaction
      between a dendrimer-covered AuNP and target protein molecules in vitro. 

PMID- 24571137
TI  - Bipolar or borderline: a clinical overview.
AB  - OBJECTIVE: To examine the empirical literature on diagnostic validators in
      borderline personality and bipolar illness. METHOD: Using principles of evidence
      based medicine, the highest levels of evidence were emphasized in interpretation
      of similarities or differences between bipolar illness and borderline personality
      on the five standard diagnostic validators in psychiatric nosology: symptoms,
      course, genetics, treatment response, and neurobiology. RESULTS: Bipolar illness
      and borderline personality were found to be similar in the nosological validator
      of symptoms of mood lability and impulsivity, but differed notably on all other
      diagnostic validators, especially the course validator of past sexual abuse and
      the genetic validator of a bipolar family history. They also differ notably in
      the symptom validator of parasuicidal self-harm. Treatment response and
      neurobiological differences were also present and consistent. CONCLUSION: This
      review of the literature indicates that these two conditions, bipolar illness and
      borderline personality, are different and can be distinguished. The much stronger
      biological and genetic evidence for bipolar illness in particular suggests that
      the two conditions can be reasonably seen as different kinds of clinical
      entities, namely a biological disease versus a psychosocially caused clinical
      picture. If this interpretation is correct, similarities between the two
      conditions, such as mood lability and impulsivity, are superficial, while
      differences are profound. Further, true comorbidity may be much less common than
      often presumed.

PMID- 24571139
TI  - Does faith have a place at work?

PMID- 24571147
TI  - Why managers are taking notice of staff happiness .

PMID- 24571148
TI  - Expression of religious beliefs still contentious in workplace.

PMID- 24571138
TI  - Linkage maps of the Atlantic salmon (Salmo salar) genome derived from RAD
      sequencing.
AB  - BACKGROUND: Genetic linkage maps are useful tools for mapping quantitative trait
      loci (QTL) influencing variation in traits of interest in a population.
      Genotyping-by-sequencing approaches such as Restriction-site Associated DNA
      sequencing (RAD-Seq) now enable the rapid discovery and genotyping of genome-wide
      SNP markers suitable for the development of dense SNP linkage maps, including in
      non-model organisms such as Atlantic salmon (Salmo salar). This paper describes
      the development and characterisation of a high density SNP linkage map based on
      SbfI RAD-Seq SNP markers from two Atlantic salmon reference families. RESULTS:
      Approximately 6,000 SNPs were assigned to 29 linkage groups, utilising markers
      from known genomic locations as anchors. Linkage maps were then constructed for
      the four mapping parents separately. Overall map lengths were comparable between
      male and female parents, but the distribution of the SNPs showed sex-specific
      patterns with a greater degree of clustering of sire-segregating SNPs to single
      chromosome regions. The maps were integrated with the Atlantic salmon draft
      reference genome contigs, allowing the unique assignment of ~4,000 contigs to a
      linkage group. 112 genome contigs mapped to two or more linkage groups,
      highlighting regions of putative homeology within the salmon genome. A
      comparative genomics analysis with the stickleback reference genome identified
      putative genes closely linked to approximately half of the ordered SNPs and
      demonstrated blocks of orthology between the Atlantic salmon and stickleback
      genomes. A subset of 47 RAD-Seq SNPs were successfully validated using a high
      throughput genotyping assay, with a correspondence of 97% between the two assays.
      CONCLUSIONS: This Atlantic salmon RAD-Seq linkage map is a resource for salmonid
      genomics research as genotyping-by-sequencing becomes increasingly common. This
      is aided by the integration of the SbfI RAD-Seq SNPs with existing reference maps
      and the draft reference genome, as well as the identification of putative genes
      proximal to the SNPs. Differences in the distribution of recombination events
      between the sexes is evident, and regions of homeology have been identified which
      are reflective of the recent salmonid whole genome duplication.

PMID- 24571149
TI  - NHS England learns lessons from Scottish colleagues on improving patient safety.

PMID- 24571150
TI  - In search of clarity.

PMID- 24571157
TI  - A pan-European network for all.

PMID- 24571161
TI  - Review of non-medical prescribing among acute and community staff.
AB  - All employers of non-medical prescribers (NMPs) have a duty to ensure they remain
      competent and current, and have access to relevant continuing professional
      development as identified through their staff appraisals. This article describes
      a survey that was undertaken to evaluate non-medical prescribing in one trust
      that operates an acute district hospital and community services. Five themes
      emerged from the results: prescribing activity, patient safety, effect of non
      medical prescribing on care, workforce planning and organisational support. The
      findings also suggested that most NMPs surveyed were compliant with local and
      national policy. Non-compliance was addressed through line manager intervention.
      Support for NMPs must be addressed at organisational level to ensure safety of
      all stakeholders.

PMID- 24571162
TI  - Ten years of transfusion practitioners and better blood transfusion in Scotland.
AB  - After the Department of Health's Better Blood Transfusion recommendations ( DH
      2002 ) ten years ago, a network of 18 transfusion practitioners supported by a
      central team in the Scottish National Blood Transfusion Service was established.
      This article discusses the impact that transfusion practitioners in Scotland have
      had in driving local transfusion teams to promote safe and effective transfusion
      practice across Scotland. They have done this through education, audit and
      raising awareness of current guidelines. 

PMID- 24571163
TI  - Self-management in chronic conditions: partners in health scale instrument
      validation.
AB  - AIMS: This article describes a study that aimed to validate the Self-care in
      Chronic Conditions Partners in Health Scale instrument in the Mexican population.
      The instrument has been validated in Australia for use as a screening tool by
      primary healthcare professionals to assess the self-care skills and abilities of
      people with a chronic illness. METHODS: Validation was conducted using baseline
      data for 552 people with diabetes, hypertension and cancer aged 18 or older who
      were users of healthcare centres in Tampico, Tamaulipas, Mexico. RESULTS: Results
      show high reliability and validity of the instrument and three themes were
      identified: knowledge, adherence, and dealing with and managing side effects.
      CONCLUSION: The findings suggest the scale is useful as a generic self-rated
      clinical tool for assessing self-management in a range of chronic conditions, and
      provides an outcome measure for comparing populations and change in patient self
      management knowledge and behaviour. The authors recommend validating the scale in
      other Latin-American settings with more research into the effect of gender on
      self- management.

PMID- 24571164
TI  - Different dimension.

PMID- 24571165
TI  - Targeting carnitine biosynthesis: discovery of new inhibitors against gamma
      butyrobetaine hydroxylase.
AB  - gamma-Butyrobetaine hydroxylase (BBOX) catalyzes the conversion of gamma
      butyrobetaine (GBB) to l-carnitine, which is involved in the generation of
      metabolic energy from long-chain fatty acids. BBOX inhibitor 3-(1,1,1
      trimethylhydrazin-1-ium-2-yl)propanoate (mildronate), which is an approved,
      clinically used cardioprotective drug, is a relatively poor BBOX inhibitor and
      requires high daily doses. In this paper we describe the design, synthesis, and
      properties of 51 compounds, which include both GBB and mildronate analogues. We
      have discovered novel BBOX inhibitors with improved IC50 values; the best
      examples are in the nanomolar range and about 2 orders of magnitude better when
      compared to mildronate. For six inhibitors, crystal structures in complex with
      BBOX have been solved to explain their activities and pave the way for further
      inhibitor design. 

PMID- 24571167
TI  - Sequential thiol click reactions: formation of ternary thiourethane/thiol-ene
      networks with enhanced thermal and mechanical properties.
AB  - We report the physical properties of thiol-ene networks modified with
      thiourethane or urethane linkages, either along the main chain or as a branched
      component in the network, respectively. Because of the robust and orthogonal
      nature of thiol-isocyanate and thiol-ene reactions, these networks can be formed
      in a two-step, one-pot synthesis. Resultant networks were characterized using
      dynamic mechanical analysis, mechanical testing and other complementary
      techniques. It was found that incorporating (thio)urethanes into the networks
      increased Tg, but also increased strain at break and toughness while decreasing
      cross-link density. The changes in physical properties are discussed in terms of
      a proposed dual network morphology. These facile modifications to thiol-ene
      networks demonstrate how molecular-level, nanoscale changes can have a profound
      influence on the macroscale properties through hierarchical development of
      network morphology. 

PMID- 24571166
TI  - Chronic subthreshold subdural cortical stimulation for the treatment of focal
      epilepsy originating from eloquent cortex.
AB  - Medically refractory epilepsy remains a major medical problem worldwide. Although
      some patients are eligible for surgical resection of seizure foci, a proportion
      of patients are ineligible for a variety of reasons. One such reason is that the
      foci reside in eloquent cortex of the brain and therefore resection would result
      in significant morbidity. This retrospective study reports our experience with a
      novel neurostimulation technique for the treatment of these patients. We
      identified three patients who were ineligible for surgical resection of the
      intracranially identified seizure focus because it resided in eloquent cortex,
      who underwent therapeutic trial of focal cortical stimulation delivered through
      the subdural monitoring grid. All three patients had a significant reduction in
      seizures, and two went on to permanent implantation, which resulted in long-term
      reduction in seizure frequency. In conclusion, this small case report provides
      some evidence of proof of concept of the role of targeted continuous neocortical
      neurostimulation in the treatment of medically refractory focal epilepsy, and
      provides support for ongoing investigations into this treatment modality.

PMID- 24571168
TI  - Biomechanical properties of the tomato (Solanum lycopersicum) fruit cuticle
      during development are modulated by changes in the relative amounts of its
      components.
AB  - In this study, growth-dependent changes in the mechanical properties of the
      tomato (Solanum lycopersicum) cuticle during fruit development were investigated
      in two cultivars with different patterns of cuticle growth and accumulation. The
      mechanical properties were determined in uniaxial tensile tests using strips of
      isolated cuticles. Changes in the functional groups of the cuticle chemical
      components were analysed by attenuated total reflectance-Fourier transform
      infrared (ATR-FTIR). The early stages of fruit growth are characterized by an
      elastic cuticle, and viscoelastic behaviour only appeared at the beginning of
      cell enlargement. Changes in the cutin:polysaccharide ratio during development
      affected the strength required to achieve viscoelastic deformation. The increase
      in stiffness and decrease in extensibility during ripening, related to flavonoid
      accumulation, were accompanied by an increase in cutin depolymerization as a
      result of a reduction in the overall number of ester bonds. Quantitative changes
      in cuticle components influence the elastic/viscoelastic behaviour of the
      cuticle. The cutin:polysaccharide ratio modulates the stress required to
      permanently deform the cuticle and allow cell enlargement. Flavonoids stiffen the
      elastic phase and reduce permanent viscoelastic deformation. Ripening is
      accompanied by a chemical cleavage of cutin ester bonds. An infrared (IR) band
      related to phenolic accumulation can be used to monitor changes in the cutin
      esterification index. 

PMID- 24571169
TI  - Probiotics reduce psychological stress in patients before laryngeal cancer
      surgery.
AB  - AIM: Laryngeal cancer is a common malignancy; surgery is the preferred treatment.
      Psychosocial stress is one of the negative impacts on patient recovery. This
      study aimed to elucidate the effect of probiotics on ameliorating anxiety, and on
      serum corticotropin-releasing factor (CRF) in laryngeal cancer patients before
      surgery. METHODS: A total 30 patients with laryngeal cancer and 20 healthy
      volunteers were recruited. During the 2 weeks before surgery, 20 patients were
      randomly allocated to receive probiotics or placebo twice a day. Heart rate was
      recorded daily. The degree of anxiety was assessed by the Hamilton Anxiety Scale
      (HAMA). RESULTS: Serum CRF levels in laryngeal cancer patients increased
      significantly in approaching surgery. After ingestion of probiotics, serum levels
      of CRF and heart rate did not increase before surgery. In addition, taking
      probiotics relieved the degree of anxiety of the patients from HAMA 19.8 to 10.2.
      CONCLUSION: Probiotics can ameliorate the clinical anxiety and biochemical
      features of stress in patients scheduled for laryngectomy.

PMID- 24571170
TI  - Myasthenia and risk of cancer: a population-based case-control study.
AB  - BACKGROUND AND PURPOSE: To evaluate the association between having non-thymoma
      myasthenia and the risk of extra-thymic cancer in a population-based setting.
      METHODS: A nationwide case-control study was conducted in Denmark based on
      medical registries. The study included all cases with a first time diagnosis of
      cancer during 2000-2009. Each case was matched by birth year and gender with
      eight population controls using risk set sampling. Subjects with myasthenia were
      identified through a validated register-based algorithm. Conditional logistic
      regression was used to compute crude and adjusted odds ratios (ORs), with 95%
      confidence intervals (CIs), for cancer associated with a prior diagnosis of
      myasthenia. RESULTS: In all, 233 437 cases and 1 867 009 controls were
      identified. A total of 80 cases and 518 controls had a prior diagnosis of
      myasthenia. Myasthenia was not associated with an increased risk of overall
      cancer (OR 1.1; 95% CI 0.9-1.4). Adjusted ORs for major cancer sites were also
      close to unity, whereas an elevated risk of lymphomas was observed (OR 2.0; 95%
      CI 0.8-5.5). Early-onset myasthenia was associated with a slightly increased OR
      for overall cancer (1.5; 95% CI 1.0-2.3); however, this estimate was based on
      small numbers. CONCLUSIONS: Non-thymoma myasthenia was not associated with an
      increased risk of overall cancer. Larger studies are necessary to evaluate the
      association between myasthenia and risk of lymphoma and the potential effect
      modification by age of myasthenia onset in relation to cancer risk.

PMID- 24571171
TI  - Formation of a hydrogen-bonded barbiturate [2]-rotaxane.
AB  - Interlocked structures containing the classic Hamilton barbiturate binding motif
      comprising two 2,6-diamidopyridine units are reported for the first time. Stable
      [2]-rotaxanes can be accessed either through hydrogen-bonded preorganization by a
      barbiturate thread followed by a Cu(+)-catalyzed "click" stoppering reaction or
      by a Cu(2+)-mediated Glaser homocoupling reaction. 

PMID- 24571172
TI  - Asking women about mental health and social adversity in pregnancy: results of an
      Australian population-based survey.
AB  - BACKGROUND: Social adversity undermines health in pregnancy. The objective of
      this study was to examine the extent to which pregnant women were asked about
      their mental health and life circumstances in pregnancy checkups. METHOD:
      Population-based postal survey of recent mothers in two Australian states.
      FINDINGS: Around half of the 4,366 participants reported being asked about
      depression (45.9%) and whether they were anxious or worried about things
      happening in their life (49.6%); fewer reported being asked about relationship
      issues (29.6%), financial problems (16.6%), or family violence (14.1%). One in
      five women (18%) reported significant social adversity. These women were more
      likely to recall being asked about their mental health and broader social health
      issues. Far higher levels of inquiry were reported by women in the public
      maternity system with midwives more likely than doctors to ask about mental
      health, family violence, and other social hardships. CONCLUSIONS: Routine
      pregnancy visits afford a window of opportunity for identifying and supporting
      women experiencing mental health problems and social adversity. Changing practice
      to take advantage of this opportunity will require concerted and coordinated
      efforts by practitioners and policy makers to build systems to support public
      health approaches to antenatal care.

PMID- 24571173
TI  - Heat exposure enhances radiosensitivity by depressing DNA-PK kinase activity
      during double strand break repair.
AB  - PURPOSE: From the role of double strand DNA dependent protein kinase (DNA-PKcs)
      activity of non-homologous end joining (NHEJ) repair for DNA double strand breaks
      (DSBs), we aim to define possible associations between thermo-sensitisation and
      the enzyme activities in X-ray irradiated cells. MATERIALS AND METHODS: DNA-PKcs
      deficient mouse, Chinese hamster and human cultured cells were compared to the
      parental wild-type cells. The radiosensitivities, the number of DSBs and DNA-PKcs
      activities after heat-treatment were measured. RESULTS: Both DNA-PKcs deficient
      cells and the wild-type cells showed increased radiosensitivities after heat
      treatment. The wild-type cells have two repair processes; fast repair and slow
      repair. In contrast, DNA-PKcs deficient cells have only the slow repair process.
      The fast repair component apparently disappeared by heat-treatment in the wild
      type cells. In both cell types, additional heat exposure enhanced
      radiosensitivities. Although DNA-PKcs activity was depressed by heat, the
      inactivated DNA-PKcs activity recovered during an incubation at 37  degrees C.
      DSB repair efficiency was dependent on the reactivation of DNA-PKcs activity.
      CONCLUSION: It was suggested that NHEJ is the major process used to repair X-ray
      induced DSBs and utilises DNA-PKcs activity, but homologous recombination repair
      provides additional secondary levels of DSB repair. The thermo-sensitisation in X
      ray-irradiated cells depends on the inhibition of NHEJ repair through the
      depression of DNA-PKcs activities.

PMID- 24571174
TI  - Experimental characterisation of the thermal lesion induced by microwave
      ablation.
AB  - PURPOSE: This work focuses on the characterisation of the ablated area induced by
      a microwave thermal ablation (MTA) procedure. An experimental methodology for
      establishing a straightforward correlation between the temperature gradient and
      the changes in the dielectric properties of the tissue is presented and
      discussed. MATERIALS AND METHODS: Temperature measurements were performed during
      an ablation procedure in ex vivo bovine liver, at different distances from the
      antenna, whereas measurements of complex permittivity were conducted in sagittal
      sections of the ablated samples. The measured temperatures and dielectric
      properties were then correlated to obtain the dependence of the dielectric
      properties' spatial variation on the temperature gradient. The obtained
      correlation has been validated through comparison with previously obtained
      experimental data. A weighted cubic polynomial function and a weighted sigmoid
      function have been tested for best-fit interpolation of the measured data.
      RESULTS: Temperatures in the range 23-105  degrees C were measured during the MTA
      procedure, while, after the end of the MTA trials, relative permittivities in the
      range 7-43 and electric conductivities in the range 0.3-1.8 S/m were measured
      according to the distance from the antenna's axis. The polynomial function showed
      better regression coefficients than the sigmoid one for both the relative
      permittivity (R(2 )= 0.9947 versus R(2 )= 0.9912, respectively) and the
      conductivity (R(2 )= 0.9919 versus R(2 )= 0.9866, respectively). However, the
      weighted cubic function showed an unrealistic behaviour for the relative
      permittivity at temperatures lower than 40  degrees C. CONCLUSIONS: According to
      the results obtained, information on the changes in the dielectric properties of
      the tissue under MTA treatment could be inferred from measured temperature data.
      Once validated by in vivo studies, the proposed methodology could be exploited to
      develop predictive tools for treatment planning.

PMID- 24571175
TI  - Non-invasive temperature monitoring and hyperthermic injury onset detection using
      X-ray CT during HIFU thermal treatment in ex vivo fatty tissue.
AB  - PURPOSE: This paper examines X-ray CT, to serve as an image-guiding thermal
      monitoring modality for high intensity focused ultrasound (HIFU) treatment of
      fatty tissues. MATERIALS AND METHODS: Six ex vivo porcine fat tissue specimens
      were scanned by X-ray CT simultaneously with the application of HIFU. Images were
      acquired during both heating and post-ablation stages. The temperature at the
      focal zone was measured simultaneously using a thermocouple. The mean values of
      the Hounsfield units (HU) at the focal zone were registered and plotted as a
      function of temperature. RESULTS: In all specimens studied, the HU versus
      temperature curves measured during the heating stage depicted a characteristic
      non-linear parabolic trajectory (R(2) > 0.87). The HU-temperature trajectory
      initially decreased to a minimum value at about 44.5  degrees C and then
      increased substantially as the heating progressed. The occurrence of this nadir
      point during the heating stage was clearly detectable. During post-ablation
      cooling, on the other hand, the HU increased monotonically with the decreasing
      temperature and depicted a clearly linear trajectory (R(2) >= 0.9). CONCLUSIONS:
      Our results demonstrate that the HU-temperature curve during HIFU treatment has a
      characteristic parabolic trajectory for fat tissue that might potentially be
      utilised for thermal monitoring during HIFU ablation treatments. The clear
      detection of 44.5  degrees C, presumably marking the onset of hyperthermic
      injury, can be detected non-invasively as an occurrence of a minimum on the HU
      time curve without any need to relate the HU directly to temperature. Such
      features may be helpful in monitoring and optimising HIFU thermal treatment for
      clinically applicable indications such as in the breast by providing a non
      invasive monitoring of tissue damage.

PMID- 24571176
TI  - Efficacy and safety of artificial ascites in assisting percutaneous microwave
      ablation of hepatic tumours adjacent to the gastrointestinal tract.
AB  - PURPOSE: This study assessed the efficacy and safety of artificial ascites in
      assisting ultrasound-guided percutaneous microwave (MW) ablation of hepatic
      tumours adjacent to the gastrointestinal tract. MATERIALS AND METHODS: In total,
      36 patients with 36 hepatic malignancies who underwent the introduction of
      artificial ascites before ultrasound-guided percutaneous MW ablation were
      included in this retrospective study. The separation success rate of the
      artificial ascites, the technique effectiveness of the MW ablation, local tumour
      progression and complications were assessed. RESULTS: The separation success rate
      of the artificial ascites for 36 hepatic tumours adjacent to the gastrointestinal
      tract was 88.9% (32/36). The technical effectiveness of MW ablation in 32 cases
      with successful separation was 96.9% (31/32). During follow-up (mean, 12.1 +/-
      7.2 months), local tumour progression was found in five of 31 patients (16.1%).
      One patient experienced a major complication (infection of the hepatic ablation
      zone). CONCLUSIONS: Ultrasound-guided percutaneous MW ablation assisted by
      artificial ascites is a safe and effective method for the treatment of primary
      and metastatic hepatic tumours adjacent to the gastrointestinal tract and can
      achieve good local control of such tumours.

PMID- 24571177
TI  - Validation of MR thermometry: method for temperature probe sensor registration
      accuracy in head and neck phantoms.
AB  - PURPOSE: Magnetic resonance thermometry (MRT) is an attractive means to non
      invasively monitor in vivo temperature during head and neck hyperthermia
      treatments because it can provide multi-dimensional temperature information with
      high spatial resolution over large regions of interest. However, validation of
      MRT measurements in a head and neck clinical set-up is crucial to ensure the
      temperature maps are accurate. Here we demonstrate a unique approach for
      temperature probe sensor localisation in head and neck hyperthermia test
      phantoms. METHODS: We characterise the proton resonance frequency shift
      temperature coefficient and validate MRT measurements in an oil-gel phantom by
      applying a combination of MR imaging and 3D spline fitting for accurate probe
      localisation. We also investigate how uncertainties in both the probe
      localisation and the proton resonance frequency shift (PRFS) thermal coefficient
      affect the registration of fibre-optic reference temperature probe and MRT
      readings. RESULTS: The method provides a two-fold advantage of sensor
      localisation and PRFS thermal coefficient calibration. We provide experimental
      data for two distinct head and neck phantoms showing the significance of this
      method as it mitigates temperature probe localisation errors and thereby
      increases accuracy of MRT validation results. CONCLUSIONS: The techniques
      presented here may be used to simplify calibration experiments that use an
      interstitial heating device, or any heating method that provides rapid and
      spatially localised heat distributions. Overall, the experimental verification of
      the data registration and PRFS thermal coefficient calibration technique provides
      a useful benchmarking method to maximise MRT accuracy in any similar context.

PMID- 24571178
TI  - Ultrasound-guided percutaneous microwave ablation of solitary T1N0M0 papillary
      thyroid microcarcinoma: initial experience.
AB  - PURPOSE: The aim of this study was to evaluate the feasibility, safety and
      efficacy of ultrasound-guided percutaneous microwave (MW) ablation for solitary
      T1N0M0 papillary thyroid microcarcinoma. MATERIALS AND METHODS: A total of 21
      patients (six men and 15 women; age range, 29-81 years; mean, 52.1 +/- 13.6
      years) with 21 nodules of pathologically proven solitary papillary carcinoma 3.7
      to 10.0 mm in diameter without clinically apparent lymph node, or distant
      metastasis at diagnosis (T1N0M0) were treated with MW ablation in our department.
      Microwaves were emitted at 40 W for 400 s and prolonged as necessary to attain
      confluent ablation zones. All patients were treated with levothyroxine after MW
      ablation to maintain thyroid stimulating hormone (TSH) levels below 0.1 mU/L.
      Follow-up consisted of ultrasound in 21 patients, biopsy in five patients, and
      surgical treatment in three patients. RESULTS: Four patients complained of
      hoarseness immediately after the MW ablation procedure, and all of them recovered
      within 3 months spontaneously. All tumours were completely ablated at a single
      session and no serious or permanent complications occurred. No recurrence at the
      treatment site and no distant metastases were detected, with a mean follow-up of
      11 months. Histological examination showed no evidence of a tumour in the treated
      lesions in eight patients. Follow-up ultrasound examinations showed disappearance
      of previously detected colour Doppler flow, as well as mass shrinkage, or both.
      CONCLUSION: During the short-term follow-up period, ultrasound-guided
      percutaneous MW ablation appears to be a safe and effective technique for
      solitary T1N0M0 papillary thyroid microcarcinoma.

PMID- 24571180
TI  - Modeling of nitrous oxide production by autotrophic ammonia-oxidizing bacteria
      with multiple production pathways.
AB  - Autotrophic ammonia oxidizing bacteria (AOB) have been recognized as a major
      contributor to N2O production in wastewater treatment systems. However, so far
      N2O models have been proposed based on a single N2O production pathway by AOB,
      and there is still a lack of effective approach for the integration of these
      models. In this work, an integrated mathematical model that considers multiple
      production pathways is developed to describe N2O production by AOB. The pathways
      considered include the nitrifier denitrification pathway (N2O as the final
      product of AOB denitrification with NO2(-) as the terminal electron acceptor) and
      the hydroxylamine (NH2OH) pathway (N2O as a byproduct of incomplete oxidation of
      NH2OH to NO2(-)). In this model, the oxidation and reduction processes are
      modeled separately, with intracellular electron carriers introduced to link the
      two types of processes. The model is calibrated and validated using experimental
      data obtained with two independent nitrifying cultures. The model satisfactorily
      describes the N2O data from both systems. The model also predicts shifts of the
      dominating pathway at various dissolved oxygen (DO) and nitrite levels,
      consistent with previous hypotheses. This unified model is expected to enhance
      our ability to predict N2O production by AOB in wastewater treatment systems
      under varying operational conditions. 

PMID- 24571181
TI  - Novel combination therapy with imiquimod and sorafenib for renal cell carcinoma.
AB  - OBJECTIVES: To investigate whether the combination of the imidazoquinoline immune
      response modifier, imiquimod, and the multitargeted tyrosine-kinase inhibitor,
      sorafenib, inhibits the growth of renal cell carcinoma in mice. METHODS: Female
      BALB/c mice were implanted subcutaneously with 2 * 10(5) RENCA mouse kidney
      cancer cells, and were treated with transcutaneously applied cream containing
      imiquimod and oral administrations of sorafenib beginning 5 days after
      implantation of the cells. Tumor incidence and burden were determined at 28 days
      after initiation of therapy. T cell infiltration in the tumor was determined by
      immunofluorescence staining with anti-CD3-epsilon and CD8-alpha antibodies.
      RESULTS: Therapy with imiquimod, sorafenib or their combination was well
      tolerated. Combination therapy with imiquimod and sorafenib significantly
      inhibited tumor growth when compared with administration of control vehicle,
      imiquimod or sorafenib alone (P < 0.05). The CD3- and CD8-positive T cells
      infiltrated into tumors to a greater degree in response to the combination
      therapy when compared with tumors treated with control vehicle or sorafenib
      alone. CONCLUSIONS: Combination therapy with a tyrosine-kinase inhibitor and an
      imidazoquinoline could be a promising therapeutic strategy for patients with
      renal cell carcinoma.

PMID- 24571183
TI  - Foreword to Advances in Meditation Research: neuroscience and clinical
      applications.

PMID- 24571184
TI  - Effects of 12 weeks of dynamic strength training with local vibration.
AB  - The purpose of this study was to investigate the chronic effects of dynamic
      strength training (ST) with local vibration on the maximum strength of elbow
      flexor muscles. Twenty healthy male untrained volunteers were divided randomly
      into the following two groups: the conventional training group (CTG) or the
      vibration training group (VTG). Both groups performed ST for 12 weeks, three
      times a week. The ST protocol included four sets of 8-10 repetition maximums
      (RMs) of unilateral elbow flexion exercise. The VTG performed this training
      protocol with local vibration at a frequency of 30 Hz and amplitude of 6 mm. The
      mean values of the one repetition maximum (1RM) tests for both groups increased
      significantly from the pretest week to the fourth week and from the fourth week
      to the eighth week (CTG: mean 19.02, s = 7.88%, p = 0.01; mean 10.50, s = 6.86%,
      p = 0.019, respectively; VTG: mean 16.02, s = 8.30%, p = 0.017; mean 12.55, s =
      8.76%, p = 0.019, respectively). The increases in the maximal voluntary
      contraction (MVC) tests were also statistically significant from the pretest week
      to the fourth week and from the fourth week to the eighth week (CTG: mean 12.32,
      s = 8.33%, p = 0.004; mean 9.95, s = 5.32%, p = 0.006, respectively; VTG: mean
      10.16, s = 11.71%, p = 0.003; mean 10.36, s = 2.96%, p = 0.01, respectively).
      There was no significant difference between the 1RM and MVC test results in the
      eighth and twelfth weeks in either group. No significant differences were
      observed between the groups (p < 0.05). In conclusion, the application of local
      vibration does not change the chronic effects of dynamic ST in untrained
      individuals.

PMID- 24571185
TI  - Simple benchmark for complex dose finding studies.
AB  - While a general goal of early phase clinical studies is to identify an acceptable
      dose for further investigation, modern dose finding studies and designs are
      highly specific to individual clinical settings. In addition, as outcome-adaptive
      dose finding methods often involve complex algorithms, it is crucial to have
      diagnostic tools to evaluate the plausibility of a method's simulated performance
      and the adequacy of the algorithm. In this article, we propose a simple technique
      that provides an upper limit, or a benchmark, of accuracy for dose finding
      methods for a given design objective. The proposed benchmark is nonparametric
      optimal in the sense of O'Quigley et al. (2002, Biostatistics 3, 51-56), and is
      demonstrated by examples to be a practical accuracy upper bound for model-based
      dose finding methods. We illustrate the implementation of the technique in the
      context of phase I trials that consider multiple toxicities and phase I/II trials
      where dosing decisions are based on both toxicity and efficacy, and apply the
      benchmark to several clinical examples considered in the literature. By comparing
      the operating characteristics of a dose finding method to that of the benchmark,
      we can form quick initial assessments of whether the method is adequately
      calibrated and evaluate its sensitivity to the dose-outcome relationships.

PMID- 24571186
TI  - No signs of intracranial arterial vasoconstriction in transient global amnesia.
AB  - BACKGROUND AND PURPOSE: The current theories to explain the pathophysiology of
      transient global amnesia (TGA) involve epilepsy, migraine, and hippocampal
      ischemia which might be determined by venous congestion or arterial
      vasoconstriction triggered by Valsalva-associated maneuvers in susceptible
      individuals. METHODS: Seventy-five TGA patients [mean age 60.3 +/- 8.0 years, 44
      (59%) females] and 75 age- and gender-matched controls were enrolled into a case
      control study and underwent extracranial and transcranial arterial echo-color
      Doppler sonography. RESULTS: Intracranial arterial obstructions of the posterior
      circulation were neither observed in TGA patients nor in controls. There was no
      significant difference between the two groups with regard to intima-media
      thickness of the common carotids (.73 +/- .07 vs. .72 +/- .06), cervical vessel
      atherosclerosis (13% vs. 15%), >50% intracranial stenosis of the anterior
      circulation arteries (3% vs. 3%), resistance index values of the vertebral
      arteries at rest and during Valsalva maneuver (.69 +/- .08 vs. .67 +/- .09) and
      pulsatility index values of the major intracranial arteries at rest and during
      Valsalva maneuver. No difference in all study items was found between patients
      assessed during or soon after the TGA episode. CONCLUSIONS: Extra-intracranial
      atherosclerosis does not play a pathogenic role in TGA and no supporting evidence
      for the arterial vasoconstriction hypothesis of TGA emerged from this study.

PMID- 24571187
TI  - Parental perceptions of the learner driver log book system in two Australian
      states.
AB  - OBJECTIVE: Though many jurisdictions internationally now require learner drivers
      to complete a specified number of hours of supervised driving practice before
      being able to drive unaccompanied, very few require learner drivers to complete a
      log book to record this practice and then present it to the licensing authority.
      Learner drivers in most Australian jurisdictions must complete a log book that
      records their practice, thereby confirming to the licensing authority that they
      have met the mandated hours of practice requirement. These log books facilitate
      the management and enforcement of minimum supervised hours of driving
      requirements. METHOD: Parents of learner drivers in 2 Australian states,
      Queensland and New South Wales, completed an online survey assessing a range of
      factors, including their perceptions of the accuracy of their child's learner log
      book and the effectiveness of the log book system. RESULTS: The study indicates
      that the large majority of parents believe that their child's learner log book is
      accurate. However, they generally report that the log book system is only
      moderately effective as a system to measure the number of hours of supervised
      practice a learner driver has completed. CONCLUSIONS: The results of this study
      suggest the presence of a paradox, with many parents possibly believing that
      others are not as diligent in the use of log books as they are or that the system
      is too open to misuse. Given that many parents report that their child's log book
      is accurate, this study has important implications for the development and
      ongoing monitoring of hours of practice requirements in graduated driver
      licensing systems.

PMID- 24571188
TI  - 3,3'-Dinitroamino-4,4'-azoxyfurazan and its derivatives: an assembly of diverse N
      O building blocks for high-performance energetic materials.
AB  - On the basis of a design strategy that results in the assembly of diverse N-O
      building blocks leading to energetic materials, 3,3'-dinitroamino-4,4'
      azoxyfurazan and its nitrogen-rich salts were obtained and fully characterized
      via spectral and elemental analyses. Oxone (potassium peroxomonosulfate) is an
      efficient oxidizing agent for introducing the azoxy N-oxide functionality into
      the furazan backbone, giving a straightforward and low-cost synthetic route. On
      the basis of heats of formation calculated with Gaussian 03 and combined with
      experimentally determined densities, energetic properties (detonation velocity,
      pressure and specific impulse) were obtained using the EXPLO v6.01 program. These
      new molecules exhibit high density, moderate to good thermal stability,
      acceptable impact and friction sensitivities, and excellent detonation
      properties, which suggest potential applications as energetic materials.
      Interestingly, 3,3'-dinitroamino-4,4'-azoxyfurazan (4) has the highest calculated
      crystal density of 2.02 g cm(-3) at 173 K (gas pycnometer measured density is
      1.96 g cm(-3) at 298 K) for N-oxide energetic compounds yet reported. Another
      promising compound is the hydroxylammonium salt (6), which has four different
      kinds of N-O moieties and a detonation performance superior to those of 1,3,5,7
      tetranitrotetraazacyclooctane (HMX), and 2,4,6,8,10,12-hexanitro-2,4,6,8,10,12
      hexaazatetracyclododecane (CL-20). Furthermore, computational results, viz., NBO
      charges and ESP, also support the superior qualities of the newly prepared
      compounds and the design strategy. 

PMID- 24571182
TI  - The potential effects of meditation on age-related cognitive decline: a
      systematic review.
AB  - With a rapidly aging society it becomes increasingly important to counter normal
      age-related decline in cognitive functioning. Growing evidence suggests that
      cognitive training programs may have the potential to counteract this decline. On
      the basis of a growing body of research that shows that meditation has positive
      effects on cognition in younger and middle-aged adults, meditation may be able to
      offset normal age-related cognitive decline or even enhance cognitive function in
      older adults. In this paper, we review studies investigating the effects of
      meditation on age-related cognitive decline. We searched the Web of Science (1900
      to present), PsycINFO (1597 to present), MEDLINE (1950 to present), and CABI
      (1910 to present) to identify original studies investigating the effects of
      meditation on cognition and cognitive decline in the context of aging. Twelve
      studies were included in the review, six of which were randomized controlled
      trials. Studies involved a wide variety of meditation techniques and reported
      preliminary positive effects on attention, memory, executive function, processing
      speed, and general cognition. However, most studies had a high risk of bias and
      small sample sizes. Reported dropout rates were low and compliance rates high. We
      conclude that meditation interventions for older adults are feasible, and
      preliminary evidence suggests that meditation can offset age-related cognitive
      decline. 

PMID- 24571189
TI  - The role of self-efficacy in health coaching and health education for patients
      with type 2 diabetes.
AB  - PURPOSE: To assess the role of toothbrushing self-efficacy (TBSE) in diabetes
      management by comparing health education (HE) and health coaching (HC) in type 2
      diabetes. METHODS: The data [HbA1c , Clinical Attachment Loss (CAL), TBSE] were
      collected initially and after intervention. Participants were allocated randomly
      to HC (n = 77) and HE (n = 109) groups. RESULTS: The low TBSE subgroup showed
      greater improvement in TBSE in the HC group (?mean:23.4 +/- 9.2) than the HE
      group (?mean:12.4 +/- 10.3), (P < 0.01). The moderate TBSE group showed
      significant improvements only in the HC group (P < 0.001).There was a significant
      reduction in HbA1c and CAL in all the TBSE subgroups in HC (P < 0.05), which was
      significantly higher than in the HE groups (P < 0.05). Improvements in TBSE and
      CAL were explanatory variables for the reduction in HbA1c among the HC patients
      in all the TBSE subgroups (P < 0.05). Among HE patients, improvement in CAL was
      an explanatory variable for change at HbA1c in the low TBSE subgroup.
      CONCLUSIONS: The present findings show that HC is more effective in terms of
      reduced HbA1c and CAL compared with HE. The data suggest that HC unlocks positive
      self-intrinsic motivation, anchoring the self-efficacy/competency beliefs for
      adjustment of healthy lifestyles. Thus, TBSE may be a practical starting point
      for empowerment and more effective outcomes.

PMID- 24571190
TI  - A new theoretical approach to analyze complex processes in cytoskeleton proteins.
AB  - Cytoskeleton proteins are filament structures that support a large number of
      important biological processes. These dynamic biopolymers exist in nonequilibrium
      conditions stimulated by hydrolysis chemical reactions in their monomers. Current
      theoretical methods provide a comprehensive picture of biochemical and
      biophysical processes in cytoskeleton proteins. However, the description is only
      qualitative under biologically relevant conditions because utilized theoretical
      mean-field models neglect correlations. We develop a new theoretical method to
      describe dynamic processes in cytoskeleton proteins that takes into account
      spatial correlations in the chemical composition of these biopolymers. Our
      approach is based on analysis of probabilities of different clusters of subunits.
      It allows us to obtain exact analytical expressions for a variety of dynamic
      properties of cytoskeleton filaments. By comparing theoretical predictions with
      Monte Carlo computer simulations, it is shown that our method provides a fully
      quantitative description of complex dynamic phenomena in cytoskeleton proteins
      under all conditions. 

PMID- 24571192
TI  - Gas-phase synthesis and structure of Wade-type ruthenium carbonyl and hydrido
      carbonyl clusters.
AB  - The gas-phase reaction of size-selected Ru(n)(+) (n = 4-6) clusters with CO in an
      ion trap yields only one specific ruthenium carbonyl complex for each cluster
      size, Ru4(CO)14(+), Ru5(CO)16(+), and Ru6(CO)18(+). First-principles density
      functional theory calculations reveal structures for these hitherto unknown
      carbonyl compounds that are in perfect agreement with the geometries predicted by
      Wade's electron counting rules. Furthermore, reactions with D2 show that for
      Ru4(+) and Ru6(+), CO molecules can be partially replaced by D2 to form hydrido
      carbonyl complexes while preserving the total ligand count corresponding to the
      Wade cluster sizes.

PMID- 24571191
TI  - Obsessive-compulsive symptoms in at-risk mental states for psychosis:
      associations with clinical impairment and cognitive function.
AB  - OBJECTIVE: Obsessive-compulsive symptoms (OCS) constitute a major comorbidity in
      schizophrenia. Prevalence estimations of OCS for patients with at-risk mental
      states (ARMS) for psychosis vary largely. It is unclear how ARMS patients with or
      without comorbid OCS differ regarding general psychosocial functioning, psychotic
      and affective symptoms and neurocognitive abilities. METHOD: At-risk mental
      states patients (n = 233) from the interventional trial PREVENT (Secondary
      Prevention of Schizophrenia) were stratified according to the presence or absence
      of comorbid OCS and compared on several clinical variables. RESULTS: Patients,
      who fulfilled the criteria for obsessive-compulsive disorder (OCD) or presented
      with subclinical OCS (ARMSposOCS sample), did not significantly differ from
      patients without OCS (ARMSnegOCS) with regard to gender, age, premorbid verbal
      intelligence and levels of education. Furthermore, similar severity of depressive
      syndromes, basic cognitive, attenuated psychotic and brief limited intermittent
      psychotic symptoms were found. However, ARMSposOCS patients showed more
      impairment of psychosocial functioning and higher general psychopathology. In
      contrast, they scored higher in cognitive tasks measuring working memory and
      immediate verbal memory. CONCLUSION: Findings extend upon previous results due to
      the multidimensional assessment. Subsequent longitudinal studies might elucidate
      how comorbid OCS influence differential treatment response, especially to
      cognitive behavioural interventions and the transition rates to psychosis.

PMID- 24571193
TI  - The effect of methylnaltrexone on the side effects of intrathecal morphine after
      orthopedic surgery under spinal anesthesia.
AB  - Methylnaltrexone is a peripheral opioid receptor antagonist that does not cross
      the blood-brain barrier; so without interference with pain relief, it could
      reverse the peripheral opioid side effects such as constipation, pruritus,
      postoperative ileus, and urinary retention. This study has been designed to
      evaluate the effect of methylnaltrexone on postoperative side effects of
      intrathecal morphine. In seventy-two 18- to 55-year-old patients scheduled for
      elective orthopedic operations under spinal anesthesia, neuraxial blockade was
      achieved using 10 mg 0.5% hyperbaric bupivacaine and 0.1 mg preservative-free
      morphine sulfate. The first group (M) received 12 mg methylnaltrexone, while the
      second group (P) received normal saline, subcutaneously, immediately after spinal
      block in a randomized, double-blind fashion. There was a significant decrease in
      the rate of nausea and vomiting in group M, but there was no significant
      difference in the rate of pruritus or urinary retention between the two groups.
      Pain score was significantly lower in group M. Respiratory depression or
      decreased level of consciousness was not reported in any patient. Subcutaneous
      administration of methylnaltrexone was not effective in decreasing postoperative
      urinary retention and pruritus, but lowered the rate of nausea and vomiting and
      pain score after intrathecal bupivacaine and morphine. 

PMID- 24571195
TI  - Imidazole aldoximes effective in assisting butyrylcholinesterase catalysis of
      organophosphate detoxification.
AB  - Intoxication by organophosphate (OP) nerve agents and pesticides should be
      addressed by efficient, quickly deployable countermeasures such as antidotes
      reactivating acetylcholinesterase or scavenging the parent OP. We present here
      synthesis and initial in vitro characterization of 14 imidazole aldoximes and
      their structural refinement into three efficient reactivators of human
      butyrylcholinesterase (hBChE) inhibited covalently by nerve agent OPs, sarin,
      cyclosarin, VX, and the OP pesticide metabolite, paraoxon. Rapid reactivation of
      OP-hBChE conjugates by uncharged and nonprotonated tertiary imidazole aldoximes
      allows the design of a new OP countermeasure by conversion of hBChE from a
      stoichiometric to catalytic OP bioscavenger with the prospect of oral
      bioavailability and central nervous system penetration. The enhanced in vitro
      reactivation efficacy determined for tertiary imidazole aldoximes compared to
      that of their quaternary N-methyl imidazolium analogues is attributed to ion
      pairing of the cationic imidazolium with Asp 70, altering a reactive alignment of
      the aldoxime with the phosphorus in the OP-hBChE conjugate. 

PMID- 24571196
TI  - Nitric oxide from mononuclear cells may be involved in platelet responsiveness to
      aspirin.
AB  - BACKGROUND: Several mechanisms have been proposed to explain why some platelets
      have a reduced response to aspirin (ASA). Among them, it was reported an
      increased circulating level of vitamin-D-binding protein (DBP). In addition,
      nitric oxide (NO) released from mononuclear cells was involved in the
      antiplatelet effects of ASA. The aim was to analyse the relationship between
      platelet response to ASA and both NO generation and vitamin-D-binding protein
      content in mononuclear cells. MATERIALS AND METHODS: Mononuclear cells were
      obtained from patients with stable coronary artery disease that were divided by a
      platelet functionality test (PFA-100) as ASA-sensitive (n=23) and ASA resistant
      (n=27). RESULTS: Both the release of NO (determined by nitrite+nitrate
      concentration) and the expression of endothelial-type NO synthase (eNOS) were
      higher in mononuclear cells from ASA sensitive as compared with those from ASA
      resistant patients. There was a positive correlation between either the release
      of NO and the expression of eNOS protein in mononuclear cells with the ability of
      ASA to inhibit platelet activity. DBP content in mononuclear cells was higher in
      ASA resistant than in ASA sensitive. The level of DBP content in mononuclear
      cells was negatively associated with the ability of ASA to inhibit platelets.
      However, in vitro experiments suggested that there was no association between DBP
      and NO production by mononuclear cells. CONCLUSIONS: Mononuclear cells from
      patients with platelets with lower responsiveness to ASA showed a reduced ability
      to produce NO.

PMID- 24571199
TI  - Long-term inhibition of ethanol intake by the administration of an aldehyde
      dehydrogenase-2 (ALDH2)-coding lentiviral vector into the ventral tegmental area
      of rats.
AB  - Previous studies suggest that acetaldehyde generated from ethanol in the brain is
      reinforcing. The present studies tested the feasibility of achieving a long-term
      reduction of chronic and post-deprivation binge ethanol drinking by a single
      administration into the brain ventral tegmental area (VTA) of a lentiviral vector
      that codes for aldehyde dehydrogenase-2 (ALDH2), which degrades acetaldehyde. The
      ALDH2 gene coding vector or a control lentiviral vector were microinjected into
      the VTA of rats bred for their alcohol preference. In the chronic alcohol
      administration model, naive animals administered the control vector and
      subsequently offered 10% ethanol and water ingested 8-9 g ethanol/kg body
      weight/day. The single administration of the ALDH2-coding vector prior to
      allowing ethanol availability reduced ethanol drinking by 85-90% (P < 0.001) for
      the 45 days tested. In the post-deprivation binge-drinking model, animals that
      had previously consumed ethanol chronically for 81 days were administered the
      lentiviral vector and were thereafter deprived of ethanol for three 7-day
      periods, each interrupted by a single 60-minute ethanol re-access after the last
      day of each deprivation period. Upon ethanol re-access, control vector-treated
      animals consumed intoxicating 'binge' amounts of ethanol, reaching intakes of 2.7
      g ethanol/kg body weight in 60 minutes. The administration of the ALDH2-coding
      vector reduced re-access binge drinking by 75-80% (P < 0.001). This study shows
      that endowing the ventral tegmental with an increased ability to degrade
      acetaldehyde greatly reduces chronic alcohol consumption and post-deprivation
      binge drinking for prolonged periods and supports the hypothesis that brain
      generated acetaldehyde promotes alcohol drinking. 

PMID- 24571200
TI  - Effects of virus on plant fecundity and population dynamics.
AB  - Microorganisms are ubiquitous and thought to regulate host populations. Although
      microorganisms can be pathogenic and affect components of fitness, few studies
      have examined their effects on wild plant populations. As individual traits might
      not contribute equally to changes in population growth rate, it is essential to
      examine the entire life cycle to determine how microorganisms affect host
      population dynamics. In this study, we used data from common garden experiments
      with plants from three Cucurbita pepo populations exposed to three virus
      treatments. These data were used to parameterize a deterministic matrix model,
      which allowed us to estimate the effect of virus on components of fitness and
      population growth rate. Virus did not reduce fruit number, but population growth
      rates varied among virus treatments and wild C. pepo populations. The effect of
      virus on population growth rate depended on virus species and wild C. pepo
      population. Contributions of life-history transitions and life-history traits to
      population growth rates varied among populations and virus treatments. However,
      this population-virus interaction was not evident when examining individual
      components of fitness. Thus, caution must be used when interpreting the effects
      of changes in individual traits, as single traits do not always predict
      population-level change accurately. 

PMID- 24571201
TI  - External self-representations improve self-awareness in a child with autism.
AB  - We have previously suggested that the social symptoms of autism spectrum disorder
      (ASD) could be caused in part by a dysfunctional mirror neuron system (MNS).
      Since the recursive activity of a functioning MNS might enable the brain to
      integrate visual and motor sensations into a coherent body schema, the deficits
      in self-awareness often seen in ASD might be caused by the same mirror neuron
      dysfunction. CL is an autistic adolescent who is profoundly fascinated with his
      reflection, looking in mirrors at every opportunity. We demonstrate that CL's
      abnormal gait improves significantly when using a mirror for visual feedback. We
      also show that both the fascination and the happiness that CL derives from
      looking at a computer-generated reflection diminish when a delay is introduced
      between the camera input and screen output. We believe that immediate, real-time
      visual feedback allows CL to integrate motor sensations with external visual ones
      into a coherent body schema that he cannot internally generate, perhaps due to a
      dysfunctional MNS. 

PMID- 24571202
TI  - Density functional theory study of oxygen-atom insertion into metal-methyl bonds
      of iron(II), ruthenium(II), and osmium(II) complexes: study of metal-mediated C-O
      bond formation.
AB  - Metal-mediated C-O bond formation is a key step in hydrocarbon oxygenation
      catalytic cycles; however, few examples of this reaction have been reported for
      low-oxidation-state complexes. Oxygen insertion into a metal-carbon bond of
      Cp*M(CO)(OPy)R (Cp* = eta(5)-pentamethylcyclopentadienyl; R = Me, Ph; OPy =
      pyridine-N-oxide; M = Fe, Ru, Os) was analyzed via density functional theory
      calculations. Oxygen-atom insertions through a concerted single-step
      organometallic Baeyer-Villiger pathway and a two-step pathway via a metal-oxo
      intermediate were studied; calculations predict that the former pathway was lower
      in energy. The results indicated that functionalization of M-R to M-OR (R = Me,
      Ph) is plausible using iron(II) complexes. Starting from Cp*Fe(CO)(OPy)Ph, the
      intermediate Fe-oxo showed oxyl character and, thus, is best considered an
      Fe(III)O(*-) complex. Oxidation of the pi-acid ancillary ligand CO was facile.
      Substitutions of CO with dimethylamide and NH3 were calculated to lower the
      activation barrier by ~1-2 kcal/mol for formation of the Fe(III)O(*-)
      intermediate, whereas a chloride ligand raised the activation barrier to 26
      kcal/mol from 22.9 kcal/mol. 

PMID- 24571203
TI  - Robotic retroperitoneal partial nephrectomy: a step-by-step guide.
AB  - OBJECTIVE: To describe a step-by-step guide for successful implementation of the
      retroperitoneal approach to robotic partial nephrectomy (RPN) PATIENTS AND
      METHODS: The patient is placed in the flank position and the table fully flexed
      to increase the space between the 12th rib and iliac crest. Access to the
      retroperitoneal space is obtained using a balloon-dilating device. Ports include
      a 12-mm camera port, two 8-mm robotic ports and a 12-mm assistant port placed in
      the anterior axillary line cephalad to the anterior superior iliac spine, and 7-8
      cm caudal to the ipsilateral robotic port. RESULTS: Positioning and port
      placement strategies for successful technique include: (i) Docking robot directly
      over the patient's head parallel to the spine; (ii) incision for camera port ~1.9
      cm (1 fingerbreadth) above the iliac crest, lateral to the triangle of Petit;
      (iii) Seldinger technique insertion of kidney-shaped balloon dilator into
      retroperitoneal space; (iv) Maximising distance between all ports; (v) Ensuring
      camera arm is placed in the outer part of the 'sweet spot'. CONCLUSION: The
      retroperitoneal approach to RPN permits direct access to the renal hilum, no need
      for bowel mobilisation and excellent visualisation of posteriorly located
      tumours.

PMID- 24571204
TI  - Young women's experiences as consumers of maternity care in Queensland.
AB  - BACKGROUND: Young motherhood is commonly associated with vulnerabilities,
      stereotyping of young women's behavior, and poor outcomes for them and their
      children. The objective was to understand how maternity care is experienced by
      this group in the transition to parenthood. METHODS: Data from a large-scale 2010
      survey of women's experience of maternity care were analyzed using qualitative
      methods with open text responses. RESULTS: Overall, 7,193 women responded to the
      survey: 237 were aged 20 years or less. Most (83%) of these young women provided
      open text responses. The main themes were: "being a consumer," "the quality of
      care," "needing support," and "pride in parenthood" whereas subthemes included
      "being young" and "how staff made me feel," "testimonials for staff," "not being
      left," and "it is all worthwhile." CONCLUSION: Many young women responding
      described a positive experience. For many first-time mothers this feeling marked
      a change in their identity. Nevertheless, staff perceptions and attitudes
      affected how they saw themselves and what they took away from their experience of
      maternity care. A key message for other women is offered, supporting and
      reinforcing their role as active and involved consumers who, in engaging with
      services, have to stand up for themselves and make their needs and wishes known.

PMID- 24571205
TI  - Tadalafil 5 mg once-daily therapy for men with lower urinary tract symptoms
      suggestive of benign prostatic hyperplasia: results from a randomized, double
      blind, placebo-controlled trial carried out in Japan and Korea.
AB  - OBJECTIVES: To gain further evidence on the efficacy, safety and tolerability of
      tadalafil 5 mg once-daily in Asian men with lower urinary tract symptoms
      suggestive of benign prostatic hyperplasia. METHODS: Japanese and Korean men with
      lower urinary tract symptoms suggestive of benign prostatic hyperplasia were
      randomized to once-daily tadalafil 5 mg (n = 306) or placebo (n = 304) for 12
      weeks. RESULTS: A significantly greater improvement (P < 0.001) in total
      International Prostate Symptom Score for the change from baseline (week 0) to
      study end-point (week 12) was observed for tadalafil (-6.0) versus placebo (
      4.5). Significantly greater improvements (P < 0.01) in total International
      Prostate Symptom Score for the change from baseline to weeks 4 and 8 were
      observed for tadalafil versus placebo. Significantly greater improvements (P <
      0.05) in International Prostate Symptom Score voiding and storage subscores, and
      International Prostate Symptom Score Quality of Life Index were observed for the
      change from baseline to end-point for tadalafil versus placebo. Significantly
      greater improvements (P < 0.001) in urinary symptoms were observed for tadalafil
      versus placebo for both Patient and Clinician Global Impressions of Improvement.
      No new safety concerns were identified. CONCLUSIONS: These findings confirm the
      efficacy and safety profile of tadalafil 5 mg once-daily in Asian men with lower
      urinary tract symptoms suggestive of benign prostatic hyperplasia.

PMID- 24571207
TI  - Securing intersubjectivity through interprofessional workplace learning
      experiences.
AB  - Effective interprofessional work is premised on high levels of shared
      understandings (i.e. intersubjectivity) among those who are co-working. In
      particular, when quick or seemingly spontaneous responses are required for urgent
      or immediate action, what is termed as "shared intuition" is highly desirable.
      Much of the required intersubjectivity can arise ordinarily through everyday
      healthcare collaborations, such as through joint problem-solving. Yet, a concern
      is how best to develop these capacities in circumstances when co-working is
      temporary, fleeting and partial, and also when the goals to be achieved are
      ambiguous and uncertain, and the processes indeterminate. To achieve the kinds
      and levels of intersubjectivity required for these non-routine forms of care and
      intermittent interprofessional working, therefore, likely requires particular
      curriculum and pedagogic interventions within practice settings. These
      interventions may be used to shape the organisation and sequencing of experiences
      for interprofessional work through which can arise a foundation of shared
      understanding of concepts, procedures and values. Yet, to assist the
      articulation, sharing, appraising and elaborating shared disciplinary and
      personal-professional positions, values and procedures, specific pedagogic
      interventions may also be required, albeit their exercise being embedded in co
      working practices in healthcare work activities.

PMID- 24571208
TI  - Interprofessional education and service learning: a model for the future of
      health professions education.
AB  - The implementation of interprofessional education for healthcare professionals
      has been lackluster, at best, since it was recommended by the Institute of
      Medicine. There have been various attempts in institutions of higher learning to
      meet this goal with mixed results. Herbert Wertheim College of Medicine, Florida
      International University has developed the Green Family NeighborhoodHELPTM
      (GFNHelp) program to meet this challenge. GFNHelp is an interprofessional,
      longitudinal, service-learning program for healthcare students. Through
      participation in this program medical students team up with students from other
      professions, such as nursing, social work, and law, and collaborate to improve
      health outcomes for medically underserved families in the community. This
      educational program emphasizes the Core Competencies of the Interprofessional
      Education Collaborative through community-based service-learning, allowing
      student teams to engage firsthand and address the impact of social determinants
      on health.

PMID- 24571209
TI  - New insights into the analysis of the electrode kinetics of flavin adenine
      dinucleotide redox center of glucose oxidase immobilized on carbon electrodes.
AB  - New insights into electrochemical kinetics of the flavin adenine dinucleotide
      (FAD) redox center of glucose-oxidase (GlcOx) immobilized on reduced graphene
      oxide (rGO), single- and multiwalled carbon nanotubes (SW and MWCNT), and
      combinations of rGO and CNTs have been gained by application of Fourier
      transformed AC voltammetry (FTACV) and simulations based on a range of models. A
      satisfactory level of agreement between experiment and theory, and hence
      establishment of the best model to describe the redox chemistry of FAD, was
      achieved with the aid of automated e-science tools. Although still not perfect,
      use of Marcus theory with a very low reorganization energy (<=0.3 eV) best mimics
      the experimental FTACV data, which suggests that the process is gated as also
      deduced from analysis of FTACV data obtained at different frequencies. Failure of
      the simplest models to fully describe the electrode kinetics of the redox center
      of GlcOx, including those based on the widely employed Laviron theory is
      demonstrated, as is substantial kinetic heterogeneity of FAD species. Use of a
      SWCNT support amplifies the kinetic heterogeneity, while a combination of rGO and
      MWCNT provides a more favorable environment for fast communication between FAD
      and the electrode. 

PMID- 24571210
TI  - How have changes in front air bag designs affected frontal crash death rates? An
      update.
AB  - OBJECTIVE: Provide updated death rates comparing latest generations of frontal
      air bags in fatal crashes. METHODS: Rates of driver and right-front passenger
      deaths in frontal crashes per 10 million registered vehicle years were compared
      using Poisson marginal structural models for passenger vehicles equipped with air
      bags certified as advanced and compliant (CAC), sled-certified air bags with
      advanced features, and sled-certified air bags without any advanced features.
      Analyses of driver death rates were disaggregated by age group, gender, and belt
      use. RESULTS: CAC air bags were associated with slightly elevated frontal crash
      death rates for both drivers and right-front passengers compared to sled
      certified air bags with advanced features, but the differences were not
      statistically significant. Sled-certified air bags with advanced features were
      associated with significant benefits for drivers and for right-front passengers
      compared to sled-certified air bags without advanced features. CAC air bags were
      associated with a significant increase in belted driver death rate and a
      comparable but nonsignificant decrease in unbelted driver death rate compared to
      sled-certified air bags with advanced features. Sled-certified air bags with
      advanced features were associated with a nonsignificant 2 percent increase in
      belted driver death rate and a significant 26 percent decrease in unbelted driver
      death rate, relative to sled-certified air bags without advanced features.
      CONCLUSIONS: Implementing advanced features in sled-certified air bags was
      beneficial overall to drivers and right-front passengers with sled-certified air
      bags. No overall benefit was observed for CAC air bags compared to sled-certified
      air bags with advanced features. Further study is needed to understand the
      apparent reduction in belted driver protection observed for CAC air bags.

PMID- 24571211
TI  - Promoting equity through integrated early child development and nutrition
      interventions.
AB  - Sustainable development, a foundation of the post-2015 global agenda, depends on
      healthy and productive citizens. The origins of adult health begin early in life,
      stemming from genetic-environmental interactions that include adequate nutrition
      and opportunities for responsive learning. Inequities associated with inadequate
      nutrition and early learning opportunities can undermine children's health and
      development, thereby compromising their productivity and societal contributions.
      Transactional theory serves as a useful framework for examining the associations
      that link early child development and nutrition because it emphasizes the
      interplay that occurs between children and the environment, mediated through
      caregiver interactions. Although single interventions targeting early child
      development or nutrition can be effective, there is limited evidence on the
      development, implementation, evaluation, and scaling up of integrated
      interventions. This manuscript introduces a special edition of papers on six
      topics central to integrated child development/nutrition interventions: (1)
      review of integrated interventions; (2) methods and topics in designing
      integrated interventions; (3) economic considerations related to integrated
      interventions; (4) capacity-building considerations; (5) examples of integrated
      interventions; and (6) policy implications of integrated interventions. Ensuring
      the health and development of infants and young children through integrated child
      development/nutrition interventions promotes equity, a critical component of
      sustainable development. 

PMID- 24571212
TI  - Advantages and challenges of integration: opportunities for integrating early
      childhood development and nutrition programming.
AB  - A growing body of evidence supports the notion that integrated programs
      addressing nutrition and stimulation provide stronger impacts on nutritional and
      developmental outcomes than either intervention alone. When translating evidence
      into practice, several advantages and challenges for integration can be noted.
      Combined interventions may be more efficient than separate interventions, because
      they are intended for the same population and make use of the same facilities,
      transportation, and client contacts. In addition, for families, particularly for
      those most at risk, combined interventions can also lead to increased access to
      services. However, in order for integrated nutrition and early childhood
      development interventions to be successful, a variety of challenges must be
      addressed. These include workload of staff and supervisors, communication and
      coordination among different ministries and among staff in different sectors, and
      common language and measurement. It must be acknowledged at both the national and
      community levels that comprehensive, integrated care addressing both the physical
      and developmental needs of the child is key to promoting optimal health, growth,
      and development for children. 

PMID- 24571213
TI  - Integrating maternal psychosocial well-being into a child-development
      intervention: the five-pillars approach.
AB  - Maternal psychosocial well-being (MPW) is a wide-ranging concept that encompasses
      the psychological (e.g., mental health, distress, anxiety, depression, coping,
      problem solving) and social (e.g., family and community support, empowerment,
      culture) aspects of motherhood. Evidence-based MPW interventions that can be
      integrated into large-scale maternal and child health programs have not been
      developed. Building on several years of research in Pakistan, we developed and
      integrated a cognitive behavioral therapy-based MPW intervention (the five
      pillars approach) into a child nutrition and development program. Following
      formative research with community health workers (CHWs; n = 40) and families (n =
      37), CHWs were trained in (1) empathic listening, (2) family engagement, (3)
      guided discovery using pictures, (4) behavioral activation, and (5) problem
      solving. A qualitative feasibility study in one area demonstrated that CHWs were
      able to apply these skills effectively to their work, and the approach was found
      to be useful by CHWs, mothers, and their families. The success of the approach
      can be attributed to (1) mothers being the central focus of the intervention, (2)
      using local CHWs whom the mothers trust, (3) simplified training and regular
      supervision, and (4) an approach that facilitates, not adds, to the CHWs' work. 

PMID- 24571214
TI  - Water, sanitation, and hygiene (WASH), environmental enteropathy, nutrition, and
      early child development: making the links.
AB  - There is scarce research and programmatic evidence on the effect of poor water,
      sanitation, and hygiene (WASH) conditions of the physical environment on early
      child cognitive, sensorimotor, and socioemotional development. Furthermore, many
      common WASH interventions are not specifically designed to protect babies in the
      first 3 years of life, when gut health and linear growth are established. We
      review evidence linking WASH, anemia, and child growth, and highlight pathways
      through which WASH may affect early child development, primarily through
      inflammation, stunting, and anemia. Environmental enteropathy, a prevalent
      subclinical condition of the gut, may be a key mediating pathway linking poor
      hygiene to developmental deficits. Current early child development research and
      programs lack evidence-based interventions to provide a clean play and infant
      feeding environment in addition to established priorities of nutrition,
      stimulation, and child protection. Solutions to this problem will require
      appropriate behavior change and technologies that are adapted to the social and
      physical context and conducive to infant play and socialization. We propose the
      concept of baby WASH as an additional component of early childhood development
      programs. 

PMID- 24571215
TI  - Cost-benefit analysis of a micronutrient supplementation and early childhood
      stimulation program in Nicaragua.
AB  - This paper estimates the cost-benefit ratio for an integrated early childhood
      development program in Nicaragua (PAININ). Using longitudinal data, we estimate
      the average treatment effects of PAININ including micronutrient sprinkles on the
      prevalence of anemia and hemoglobin levels among disadvantaged children aged 6-36
      months. We also estimate the effects of PAININ excluding sprinkles on cognitive
      outcomes among children aged 2.5-5 years. In the younger age group the program
      reduced anemia by 4 percentage points after 8 months and nearly 6 percentage
      points after 1 year; the latter is a 26% decrease in anemia. In the older age
      group, the program improved verbal and numeric memory after a year and a half,
      but the effects were modest (0.13 SD). When analyzing its potential impact on
      earnings, we conclude that the discounted annual costs of the program per child
      are less than the discounted annual increase in beneficiary earnings.
      Specifically, we estimate a cost-benefit ratio of 1.50 from the PAININ plus
      sprinkles package. Our sensitivity analysis suggests a range for this ratio
      between 1.30 and 2.30. 

PMID- 24571216
TI  - Cost effectiveness of responsive stimulation and nutrition interventions on early
      child development outcomes in Pakistan.
AB  - Early childhood programs are heralded as a way to improve children's health and
      educational outcomes. However, few studies in developing countries calculate the
      effectiveness of quality early childhood interventions. Even fewer estimate the
      associated costs of such interventions. The study here looks at the costs and
      effectiveness of a cluster-randomized effectiveness trial on children from birth
      to 24 months in rural Sindh, Pakistan. Responsive stimulation and/or enhanced
      nutrition interventions were integrated in the Lady Health Worker program in
      Pakistan. Outcomes suggest that children who receive responsive stimulation had
      significantly better development outcomes at 24 months than those who only
      received enhanced nutrition intervention. A cost-effectiveness analysis of the
      results verifies that early childhood interventions that include responsive
      stimulation are more cost effective than a nutrition intervention alone in
      promoting children's early development. Costs of a responsive stimulation
      intervention integrated in an existing community-based service providing basic
      health and nutrition care is approximately US$4 per month per child. We discuss
      these findings and make recommendations about scaling up and costs for future
      early child development programs. 

PMID- 24571217
TI  - Capacity building in the health sector to improve care for child nutrition and
      development.
AB  - The effectiveness of interventions promoting healthy child growth and development
      depends upon the capacity of the health system to deliver a high-quality
      intervention. However, few health workers are trained in providing integrated
      early child-development services. Building capacity entails not only training the
      frontline worker, but also mobilizing knowledge and support to promote early
      child development across the health system. In this paper, we present the
      paradigm shift required to build effective partnerships between health workers
      and families in order to support children's health, growth, and development, the
      practical skills frontline health workers require to promote optimal caregiving,
      and the need for knowledge mobilization across multiple institutional levels to
      support frontline health workers. We present case studies illustrating challenges
      and success stories around capacity development. There is a need to galvanize
      increased commitment and resources to building capacity in health systems to
      deliver early child-development services. 

PMID- 24571218
TI  - A job analysis of community health workers in the context of integrated nutrition
      and early child development.
AB  - Stunting and poor child development are major public health concerns in Malawi.
      Integrated nutrition and early child development (ECD) interventions have shown
      potential to reduce stunting, but it is not known how these integrated approaches
      can be implemented in Malawi. In this paper, we aimed to evaluate the current
      jobs status of community health workers and their potential to implement
      integrated approaches. This was accomplished by a desk review of nutrition and
      ECD policy documents, as well as interviews with key informants, community health
      workers, and community members. We found that Malawi has comprehensive policies
      and well-outlined coordination structures for nutrition and ECD that advocate for
      integrated approaches. Strong multidisciplinary interaction exists at central
      levels but not at the community level. Integration of community health workers
      from different sectors is limited by workload, logistics, and a lack of
      synchronized work schedules. Favorable, sound policies and well-outlined
      coordination structures alone are not enough for the establishment of integrated
      nutrition and ECD activities. Balanced bureaucratic structures, improved task
      allocation, and synchronization of work schedules across all relevant sectors are
      needed for integrated intervention in Malawi. 

PMID- 24571219
TI  - Integrating early child development programs into health and nutrition services
      in Bangladesh: benefits and challenges.
AB  - Bangladesh is one of the poorest countries of the world with the highest
      population density. The Bangladesh government recognizes the educational and
      financial benefits of early childhood development (ECD) and has incorporated ECD
      into the national plan of action. However, ECD activities are not fully
      established in the country and there have been few evaluations. In this paper, we
      present ECD programs that are integrated into health and nutrition services in
      Bangladesh. We present four evaluation reports of such programs and we also
      include seven published research projects showing evidence that such integrations
      are feasible. We provide short reviews on coverage, methodology, and effects of
      the published reports and share our experience of challenges faced and steps
      taken to solve them. Overall, very few programs are based on scientific evidence
      and fewer are even evaluated. The research projects so far conducted are
      promising and there is sufficient evidence on feasibility of integrating ECD
      activities into nutrition and health programs. Suggestions are made on measures
      to overcome the implementation problems and on suitable methods to establish high
      quality ECD programs in Bangladesh and in other low- and middle-income countries.

PMID- 24571220
TI  - Strengthening systems for integrated early childhood development services: a
      cross-national analysis of governance.
AB  - While there has been substantial growth in early childhood development (ECD)
      services in low- and middle-income countries (LMICs), there is considerable
      inequity in their distribution and quality. Evidence-based governance strategies
      are necessary, but currently they are insufficient for widespread, quality
      implementation. In particular, there is a limited understanding of the use of
      systems approaches for the analysis of ECD services as they go to scale. The aim
      of this paper is to present findings from four countries, using a cross-national
      case study approach to explore governance mechanisms required to strengthen
      national systems of ECD services. While different sets of governance strategies
      and challenges were identified in each country, overarching themes also emerged
      with implications for systems strengthening. Study results focus on local, mid
      level and central governance, with recommendations for effective coordination and
      the integration of ECD services in LMICs. 

PMID- 24571221
TI  - Foreword to Every Child's Potential: integrating nutrition and early childhood
      development interventions.

PMID- 24571222
TI  - Investing in early child development: an imperative for sustainable development.

PMID- 24571223
TI  - 4,5-Dihydropyrrolo[1,2-a]quinoxalines: a tunable and regenerable biomimetic
      hydrogen source.
AB  - A series of tunable and regenerable biomimetic hydrogen sources, 4,5
      dihydropyrrolo[1,2-a]quinoxalines, have been synthesized and applied in
      biomimetic asymmetric hydrogenation of 3-aryl-2H-benzo[b][1,4]oxazines and 1
      alkyl-3-aryl-quinoxalin-2(1H)-ones, providing the chiral amines with up to 92%
      and 89% ee, respectively. 

PMID- 24571225
TI  - Intracranial arterial fenestrations associated with arteriovenous malformations
      diagnosed by CT angiography.
AB  - BACKGROUND: Fenestrations involving aneurysms have been well documented. Only
      sporadic papers have been reported on fenestrations associated with AVMs
      (arteriovenous malformations) with few cases. Our study is to determine the rate
      of co-occurrence of fenestrations and AVMs and to analyze the possible
      relationship between them by CTA. METHODS: Between January 2006 and February
      2012, the CTA data of 5,657 consecutive patients were retrospectively reviewed.
      RESULTS: A total of 12 cases (.21%) of fenestrations associated with AVMs were
      found. Of these, single-fenestrations were identified in 9 cases, and
      multifenestrations were found in 3 cases. Among 349 fenestrations, there were 15
      cases of multifenestrations. The frequency of multifenestrations among
      fenestrated patients without AVMs was 3.6%. There was no significant difference
      in the incidence of AVMs in cases with and without fenestrations (3.4% and 2.7%),
      and there was no significant difference in the incidence of fenestration in cases
      with and without AVMs (7.7% and 6.1%, chi(2) = .643, P = .423). CONCLUSIONS: CTA
      may play a vital role in assessing the anomalies of co-occurring AVM and
      fenestration, with an incidence of .21%. The frequency of multifenestrations in
      fenestrated cases with AVMs was higher than those without AVMs, though there is
      no significant association between fenestrations and AVMs.

PMID- 24571224
TI  - Semiparametric approach for non-monotone missing covariates in a parametric
      regression model.
AB  - Missing covariate data often arise in biomedical studies, and analysis of such
      data that ignores subjects with incomplete information may lead to inefficient
      and possibly biased estimates. A great deal of attention has been paid to
      handling a single missing covariate or a monotone pattern of missing data when
      the missingness mechanism is missing at random. In this article, we propose a
      semiparametric method for handling non-monotone patterns of missing data. The
      proposed method relies on the assumption that the missingness mechanism of a
      variable does not depend on the missing variable itself but may depend on the
      other missing variables. This mechanism is somewhat less general than the
      completely non-ignorable mechanism but is sometimes more flexible than the
      missing at random mechanism where the missingness mechansim is allowed to depend
      only on the completely observed variables. The proposed approach is robust to
      misspecification of the distribution of the missing covariates, and the proposed
      mechanism helps to nullify (or reduce) the problems due to non-identifiability
      that result from the non-ignorable missingness mechanism. The asymptotic
      properties of the proposed estimator are derived. Finite sample performance is
      assessed through simulation studies. Finally, for the purpose of illustration we
      analyze an endometrial cancer dataset and a hip fracture dataset.

PMID- 24571226
TI  - Trade-off between processivity and hydrolytic velocity of cellobiohydrolases at
      the surface of crystalline cellulose.
AB  - Analysis of heterogeneous catalysis at an interface is difficult because of the
      variety of reaction sites and the difficulty of observing the reaction. Enzymatic
      hydrolysis of cellulose by cellulases is a typical heterogeneous reaction at a
      solid/liquid interface, and a key parameter of such reactions on polymeric
      substrates is the processivity, i.e., the number of catalytic cycles that can
      occur without detachment of the enzyme from the substrate. In this study, we
      evaluated the reactions of three closely related glycoside hydrolase family 7
      cellobiohydrolases from filamentous fungi at the molecular level by means of high
      speed atomic force microscopy to investigate the structure-function relationship
      of the cellobiohydrolases on crystalline cellulose. We found that high moving
      velocity of enzyme molecules on the surface is associated with a high
      dissociation rate constant from the substrate, which means weak interaction
      between enzyme and substrate. Moreover, higher values of processivity were
      associated with more loop regions covering the subsite cleft, which may imply
      higher binding affinity. Loop regions covering the subsites result in stronger
      interaction, which decreases the velocity but increases the processivity. These
      results indicate that there is a trade-off between processivity and hydrolytic
      velocity among processive cellulases. 

PMID- 24571227
TI  - Environmental influence on Zn-histidine complexes under no-packing conditions.
AB  - This paper describes a combined structural analysis of the Zn-histidine complex,
      using two different and complementary techniques, X-ray absorption spectroscopy
      (XAS) and surface X-ray diffraction, paying special attention to the
      environmental conditions. The current procedure for investigating macromolecules
      consists of examining simple molecules that exhibit properties similar to those
      of the larger ones, whose functionality is totally related to the atomic
      structure. The detailed study of the bonding structure formed by zinc and
      histidine amino acids is motivated by the fact that this material serves as a
      model for metalloproteins, such as in metalloproteinase, acting as active sites
      in enzymatic or structural functions. For XAS modeling, Zn-histidine complexes
      were dissolved in several aqueous solutions, over a wide pH range. Correlations
      among the degree of protonation, the steric impediment, and the multiple
      combinations of the histidine amino acid have been found. For the diffraction
      study, high-quality crystals grown by the seeding method in a supersaturated
      solution have been studied, and the samples for the surface diffraction study
      were mounted on a cell specially designed for solid-liquid or solid-gas interface
      analysis. The surface structural model was built from XAS results. In both cases,
      the obtained structures are compared with the bulk one, showing atomic
      differences and highlighting the importance of the environment in which the
      complex is studied. 

PMID- 24571228
TI  - Oral hygiene practices among middle-school students in 44 low- and middle-income
      countries.
AB  - OBJECTIVE: To examine the frequency of toothbrushing or cleaning among middle
      school students from 44 low- and middle-income countries. METHODS: Secondary
      analysis of nationally representative data from 146,462 middle school students
      who participated in the Global School-based Student Health Survey (GSHS) between
      2003 and 2010. RESULTS: In 39 of the 44 countries, more than 80% of students
      reported brushing or cleaning their teeth at least once each day. In 23
      countries, more than 5% of participants reported brushing their teeth less than
      once a day or never. In 37 countries, boys reported a significantly lower
      frequency of toothbrushing or cleaning than did girls. Countries where miswak
      (chewing stick) use is common reported lower toothbrushing or cleaning frequency,
      perhaps because the questionnaire item did not clarify that this counts as a form
      of tooth cleaning. CONCLUSION: School-based dental health education programmes
      that target early adolescents may help students to develop habits that improve
      their immediate and long-term health.

PMID- 24571229
TI  - Recent radiation within Y-chromosomal haplogroup R-M269 resulted in high Y-STR
      haplotype resemblance.
AB  - Y-chromosomal short tandem repeats (Y-STRs) are often used in addition to Y
      chromosomal single-nucleotide polymorphisms (Y-SNP) to detect subtle patterns in
      a population genetic structure. There are, however, indications for Y-STR
      haplotype resemblance across different subhaplogroups within haplogroup R1b1b2 (R
      M269) which may lead to erosion in the observation of the population genetic
      pattern. Hence the question arises whether Y-STR haplotypes are still informative
      beyond high-resolution Y-SNP genotyping for population genetic studies. To
      address this question, we genotyped the Y chromosomes of more than 1000 males
      originating from the West-European regions of Flanders (Belgium), North-Brabant
      and Limburg (the Netherlands) at the highest resolution of the current Y-SNP tree
      together with 38 commonly used Y-STRs. We observed high resemblance of Y-STR
      haplotypes between males belonging to different subhaplogroups of haplogroup R
      M269. Several subhaplogroups within R-M269 could not be distinguished from each
      other based on differences in Y-STR haplotype variation. The most likely
      hypothesis to explain this similarity of Y-STR haplotypes within the population
      of R-M269 members is a recent radiation where various subhaplogroups originated
      within a relatively short time period. We conclude that high-resolution Y-SNP
      typing rather than Y-STR typing might be more useful to study population genetic
      patterns in (Western) Europe. 

PMID- 24571230
TI  - A family-based robust multivariate association test using maximum statistic.
AB  - For characterizing the genetic mechanisms of complex diseases familial data with
      multiple correlated quantitative traits are usually collected in genetic studies.
      To analyze such data, various multivariate tests have been proposed to
      investigate the association between the underlying disease genes and the multiple
      traits. Although these multivariate association tests may have better power
      performance than the univariate association tests, they suffer from loss of
      testing power when the genetic models of the putative genes are misspecified. To
      address the problem, in this paper we aim to develop a family-based robust
      multivariate association test. We will first establish the optimal multivariate
      score tests for the recessive, additive, and dominant genetic models. Based on
      these optimal tests, a maximum-type robust multivariate association test is then
      obtained. Simulations are conducted to compare the power of our method with that
      of other existing multivariate methods. The results show that the robust
      multivariate test does manifest the robustness in power over all plausible
      genetic models. A practical data set is applied to demonstrate the applicability
      of our approach. The results suggest that the robust multivariate test is more
      powerful than the robust univariate test when dealing with multiple quantitative
      traits. 

PMID- 24571231
TI  - Utilising family-based designs for detecting rare variant disease associations.
AB  - Rare genetic variants are thought to be important components in the causality of
      many diseases but discovering these associations is challenging. We demonstrate
      how best to use family-based designs to improve the power to detect rare variant
      disease associations. We show that using genetic data from enriched families
      (those pedigrees with greater than one affected member) increases the power and
      sensitivity of existing case-control rare variant tests. However, we show that
      transmission- (or within-family-) based tests do not benefit from this
      enrichment. This means that, in studies where a limited amount of genotyping is
      available, choosing a single case from each of many pedigrees has greater power
      than selecting multiple cases from fewer pedigrees. Finally, we show how a pseudo
      case-control design allows a greater range of statistical tests to be applied to
      family data. 

PMID- 24571232
TI  - The effects of fasting in Muslim patients taking warfarin: comment.

PMID- 24571233
TI  - Validation of continuous clinical indices of cardiometabolic risk in a cohort of
      Australian adults.
AB  - BACKGROUND: Indicators of cardiometabolic risk typically include non-clinical
      factors (e.g., smoking). While the incorporation of non-clinical factors can
      improve absolute risk prediction, it is impossible to study the contribution of
      non-clinical factors when they are both predictors and part of the outcome
      measure. Metabolic syndrome, incorporating only clinical measures, seems a
      solution yet provides no information on risk severity. The aims of this study
      were: 1) to construct two continuous clinical indices of cardiometabolic risk
      (cCICRs), and assess their accuracy in predicting 10-year incident cardiovascular
      disease and/or type 2 diabetes; and 2) to compare the predictive accuracies of
      these cCICRs with existing risk indicators that incorporate non-clinical factors
      (Framingham Risk Scores). METHODS: Data from a population-based biomedical cohort
      (n = 4056) were used to construct two cCICRs from waist circumference, mean
      arteriole pressure, fasting glucose, triglycerides and high density lipoprotein:
      1) the mean of standardised risk factors (cCICR-Z); and 2) the weighted mean of
      the two first principal components from principal component analysis (cCICR-PCA).
      The predictive accuracies of the two cCICRs and the Framingham Risk Scores were
      assessed and compared using ROC curves. RESULTS: Both cCICRs demonstrated
      moderate accuracy (AUCs 0.72 - 0.76) in predicting incident cardiovascular
      disease and/or type 2 diabetes, among men and women. There were no significant
      differences between the predictive accuracies of the cCICRs and the Framingham
      Risk Scores. CONCLUSIONS: cCICRs may be useful in research investigating
      associations between non-clinical factors and health by providing suitable
      alternatives to current risk indicators which include non-clinical factors.

PMID- 24571235
TI  - Participant supervision: supervisor and supervisee experiences of cotherapy.
AB  - Participant supervision is a unique application of live supervision in which a
      supervisor and supervisee see clients conjointly. Although minimally discussed in
      the family therapy literature, it has notable advantages, chief among them being
      a shared clinical experience that increases attunement to supervisee skill and
      development, the modeling of skillful intervention, and a higher degree of
      collegiality. However, it is not without its challenges, including supervisee
      vulnerability and anxiety, diffusion of responsibility, and limited time for case
      discussion. This article highlights the experience of one supervisor and three
      doctoral-level supervisees engaging in participant supervision over the course of
      a 2-year period. Using illustrative examples, we discuss our experience of the
      advantages and challenges of participant supervision, and provide recommendations
      for establishing a collaborative relational context within which supervisory
      benefits can be maximized. 

PMID- 24571236
TI  - On the evolution of migration in heterogeneous environments.
AB  - Populations often experience variable conditions, both in time and space. Here we
      develop a novel theoretical framework to study the evolution of migration under
      the influence of spatially and temporally variable selection and genetic drift.
      First, we examine when polymorphism is maintained at a locus under heterogeneous
      selection, as a function of the pattern of spatial heterogeneity and the
      migration rate. In a second step, we study how levels of migration evolve under
      the joint action of kin competition and local adaptation at a polymorphic locus.
      This analysis reveals the existence of evolutionary bistability, whereby a low or
      a high migration rate may evolve depending on the initial conditions. Last, we
      relax several assumptions regarding selection heterogeneity commonly made in
      previous studies and explore the consequences of more complex spatial and
      temporal patterns of variability in selection on the evolution of migration. We
      found that small modifications in the pattern of environmental heterogeneity may
      have dramatic effects on the evolution of migration. This work highlights the
      importance of considering more general scenarios of environmental heterogeneity
      when studying the evolution of life-history traits in ecologically complex
      settings. 

PMID- 24571237
TI  - A survey of the frequency of aminoglycoside antibiotic-resistant genotypes and
      phenotypes in Escherichia coli in broilers with septicaemia in Hebei, China.
AB  - 1. The aim of this study was to investigate the occurrence of aminoglycoside
      resistance and the prevalence of 6 important modifying enzyme genes, i.e. (strA,
      strB, aph(3')-IIa, aac(3)-IIa, aac(6')-Ib and ant(3")-Ia), in Escherichia coli
      strains in broilers with septicaemia in Hebei, China. 2. A total of 111 clinical
      isolates of E. coli were collected from 46 large-scale farms. Antimicrobial
      susceptibility tests, using the Kirby-Bauer disc diffusion method, were performed
      on all 111 isolates. In addition, all were screened for the presence of modifying
      enzyme genes using the polymerase chain reaction (PCR). 3. The results show that
      the rates of resistance were as follows: streptomycin: 97.3%, kanamycin: 97.0%,
      gentamicin: 95.5%, neomycin: 50.5%, amikacin: 46.0%, spectinomycin: 22.5%. Of the
      genes examined, strB (73.9%) was the most frequently identified gene in the
      phenotypic resistant isolates, followed in order by: ant(3")-Ia, aac(3)-IIa,
      aac(6')-Ib, aph(3')-IIa and strA. 4. It is concluded that aminoglycoside
      resistance in E. coli from broilers with septicaemia remains a serious problem in
      Hebei, China. This emphasises the need to ban the non-therapeutic use of
      antibiotics, discourage their misuse and to be continually vigilant by providing
      appropriate scientific and technological support for the poultry industry.

PMID- 24571238
TI  - Thermoresponsive worms for expansion and release of human embryonic stem cells.
AB  - The development of robust suspension cultures of human embryonic stem cells
      (hESCs) without the use of cell membrane disrupting enzymes or inhibitors is
      critical for future clinical applications in regenerative medicine. We have
      achieved this by using long, flexible, and thermoresponsive polymer worms
      decorated with a recombinant vitronectin subdomain that bridge hESCs, aiding in
      hESC's natural ability to form embryoid bodies (EBs) and satisfying their
      inherent requirement for cell-cell and cell-extracellular matrix contact. When
      the EBs reached an optimal upper size where cytokine and nutrient penetration
      becomes limiting, these long and flexible polymer worms facilitated EB breakdown
      via a temperature shift from 37 to 25  degrees C. The thermoresponsive nature of
      the worms enabled a cyclical dissociation and propagation of the cells. Repeating
      the process for three cycles (over eighteen days) provided a >30-fold expansion
      in cell number while maintaining pluripotency, thereby providing a simple,
      nondestructive process for the 3D expansion of hESC. 

PMID- 24571234
TI  - Scrutinizing the scaffolds of marine biosynthetics from different source
      organisms: Gram-negative cultured bacterial products enter center stage.
AB  - Compounds from macro marine organisms are presumed to owe their biosynthetic
      origins to associated microbial symbionts, although few definitive examples
      exist. An upsurge in the recent literature from 2012 to 2013 has shown that four
      compounds previously reported from macro marine organisms are in fact
      biosynthesized by non-photosynthetic Gram-negative bacteria (NPGNB). Structural
      parallels between compounds isolated from macro marine organisms and NPGNB
      producers form the basis of this review. Although less attention has been given
      to investigating the chemistry of NPGNB sources, there exists a significant list
      of structural parallels between NPGNB and macro marine organism-derived
      compounds. Alternatively, of the thousands of compounds isolated from Gram
      positive actinomycetes, few structural parallels with macro marine organisms are
      known. A summary of small molecules isolated from marine NPGNB sources is
      presented, including compounds isolated from marine myxobacteria. From this
      assemblage of structural parallels and diverse chemical structures, it is
      hypothesized that the potential for the discovery of inspirational molecules from
      NPGNB sources is vast and that the recent spike in the literature of macro marine
      compounds owing their biosynthetic origin to NPGNB producers represents a turning
      point in the field. 

PMID- 24571240
TI  - Soil freezing and N deposition: transient vs multi-year effects on plant
      productivity and relative species abundance.
AB  - Plant responses to increased atmospheric nitrogen (N) deposition must be
      considered in the context of a rapidly changing climate. Reductions in snow cover
      with climate warming can increase the exposure of herbaceous plants to freezing,
      but it is unclear how freezing damage may interact with increased N availability,
      and to what extent freezing effects may extend over multiple years. We explored
      potential interactions between freezing damage and N availability in the context
      of plant productivity and relative species abundance in a temperate old field
      using both snow removal and mesocosm experiments, and assessed the legacy effects
      of the freezing damage over 3 yr. As expected, N addition increased productivity
      and freezing damage decreased productivity, but these factors were nonadditive; N
      addition increased productivity disproportionately in the snow removal plots,
      whereas extreme freezing diminished N addition responses in the mesocosm
      experiment. Freezing altered relative species abundances, although only the most
      severe freezing treatments exhibited legacy effects on total productivity over
      multiple growing seasons. Our results emphasize that while both increased N
      deposition and freezing damage can have multi-year effects on herbaceous
      communities, the interactions between these global change factors are contingent
      on the intensities of the treatments.

PMID- 24571239
TI  - A new hypofractionated schedule of weekly irradiation for basal cell carcinoma of
      the head and neck skin area in elderly patients.
AB  - The effectiveness of radiotherapy in patients with basal cell carcinoma (BCC) has
      been already reported in the literature. However, there is little information
      about the irradiation of BCC in elderly patients, especially due to the low
      conformity of them to daily irradiation. Thirty-eight retrospectively selected
      elderly patients (78 years as median age) diagnosed with skin BCC of the head and
      neck area were treated with five weekly fractions of 600 cGy by three-dimensional
      conformal radiotherapy (3DCRT) as an adjuvant treatment. The primary endpoint was
      the relapse free survival. Acute toxicity, as secondary endpoint, was assessed
      according to EORTC/RTOG criteria. Among our patients, there were only three local
      recurrences at 15, 32 and 38 months post-3DCRT. There was no severe toxicity,
      while only 10 out of 38 patients presented grade II/III skin toxicity. Our
      proposed irradiation schedule seems effective in terms of local control and acute
      toxicity and could be an alternative scheme for elderly patients unfit for daily
      irradiation.

PMID- 24571244
TI  - Impact of laparoscopic radical prostatectomy on clinical T3 prostate cancer:
      experience of a single centre with long-term follow-up.
AB  - OBJECTIVE: To investigate the oncological safety and effectiveness of
      laparoscopic radical prostatectomy (LRP) for patients with clinical T3 (cT3)
      prostate cancer compared with patients with cT1 and cT2 prostate cancer. PATIENTS
      AND METHODS: In all, 2375 consecutive LRPs were evaluated between 1999 and 2013.
      Of the 1751 patients enrolled with complete follow-up data (>24 months), patients
      were divided into three groups according to clinical stage of prostate cancer
      using Tumour-Node-Metastasis (TNM) classification. Group 1 consisted of patients
      with cT1 stage prostate cancer, group 2 those with cT2, and group 3 those with
      cT3. Demographic, postoperative, and long-term data of patients were recorded and
      statistical analyses were performed. RESULTS: The mean (SD) age was 63.6 (6.2)
      years. The mean (SD) follow-up was 104 (28.4) months. There were 417 patients in
      group 1, 842 patients in group 2, and 492 patients in group 3. The mean prostate
      specific antigen level, biopsy Gleason score, tumour volume, body mass index, and
      age, were all higher in group 3 (P < 0.001). Nerve-sparing techniques were used
      more in group 1 than in the other groups (P < 0.001). Extracapsular extension,
      seminal vesicle invasion, Gleason score, positive surgical margin (PSM), and rate
      of adjuvant hormone and radiotherapies were highest in group 3. However, urinary
      continence was similar in all groups. Group 1 contained the most patients with an
      erection sufficient for intercourse. Group 1 had the best cancer-specific
      survival rate, whereas overall survival (OS) rates and complications were similar
      in all groups. CONCLUSION: LRP seems effective and safe for patients with cT3
      prostate cancer with similar OS rates as for those with cT1 and cT2; however,
      additional therapies may have contributed to these rates. LRP can be considered
      for the treatment of patients with cT3 prostate cancer.

PMID- 24571245
TI  - Multi-drug-resistant enterotoxigenic and enterohemorrhagic Escherichia coli
      isolated from children with diarrhea.
AB  - Multi-drug-resistant (MDR) diarrheagenic Escherichia coli (DEC) has rapidly
      spread worldwide and represents the most serious threat to the management of
      diarrhea in developing countries. During the period from March 2011 to January
      2012, a total of 450 stool samples of diarrheal children aged 0-60 months were
      studied. In order to detect enterotoxigenic E. coli (ETEC) and enterohemorrhagic
      E. coli (EHEC) simultaneously, a mixture of four primer pairs specific for eltB,
      estA, vt1, and vt2 genes was used in a multiplex PCR. Antimicrobial
      susceptibility testing was performed as the Clinical and Laboratory Standards
      Institute (CLSI) guidelines. A total of 140 (31.1%) DEC were isolated from 450
      stool samples. Diarrheagenic E. coli exhibited high-level resistance to aztreonam
      (80.7%), amoxicillin (74.4%), and tetracycline (69.3%). Also, 86.4% of E. coli
      isolates were resistant to at least three different classes of antimicrobial
      agents and considered as MDR. The frequency of ETEC and EHEC pathotypes was 46.4
      and 12.1%, respectively and all of these isolates were MDR. In conclusion, MDR
      ETEC continues to be an important agent associated with diarrhea in children from
      Tabriz, Iran. 

PMID- 24571246
TI  - Near fatal 5-FU gut toxicity post surgery--remarkable effect of high-dose
      sucralfate.
AB  - BACKGROUND: The objective of this review article and case report was to
      investigate the effectiveness of high-dose sucralfate on severe life-threatening
      5-fluorouracil (5-FU) gut toxicity, with reference to, but not limited to
      dihydropyrimidine dehydrogenase (DPD) deficiency. METHODS: A search was conducted
      on PubMed from 1950 to July 2013 for original studies on 5-FU gut toxicity and
      sucralfate. Studies were limited to human trials and English language and all
      articles included in this study were assessed with the application of
      predetermined selection criteria. Each article was then reviewed independently by
      two reviewers. A case report from our own centre was included in this review.
      RESULTS: From 33 results, 6 manuscripts were identified including 4 randomized
      controlled trial. One trial evaluated the use of sucralfate to alleviate
      stomatitis in patients with 5-FU-based chemotherapy. The other three trials
      evaluated the role of sucralfate in radiation toxicity. There was one case report
      which showed gastroscopy confirmed normalization of severe dysplastic erosive
      gastroduodenitis attributed to hepatic arterial infusion of 5-FU following a 2
      month course of sucralfate and cimetidine and one case series showing clinical
      and sigmoidoscopically demonstrated improvement in ulcerative colitis in majority
      of patients receiving sucralfate enemas. There was no current literature
      specifically focussed on the role of sucralfate in 5-FU gut toxicity. Our case
      report describes the clinical course and successful treatment with sucralfate of
      a patient with Pseudomyxoma peritonei (PMP) who experienced 5-FU gut toxicity
      resulting in life-threatening bleeding due to presumed DPD deficiency post
      intraperitoneal 5-FU administration. CONCLUSION: This review article showed a
      lack of literature concerning the use of sucralfate in 5-FU gut toxicity. In our
      patient's case, sucralfate had a crucial role in the management of near fatal 5
      FU gut toxicity, and further evaluation is required.

PMID- 24571247
TI  - Meropenem delirium: a previously unrecognized neurologic side effect.

PMID- 24571248
TI  - Molecular characterization of integrons in clinical isolates of betalactamase
      producing Escherichia coli and Klebsiella pneumoniae in Iran.
AB  - Integrons are considered to play a significant role in the evolution and spread
      of antibiotic resistance genes. A total of 349 clinical isolates of Escherichia
      coli and Klebsiella pneumoniae were investigated for molecular characterization
      of integrons and betalactamases. Antimicrobial susceptibility testing was also
      performed as the Clinical and Laboratory Standards Institute (CLSI) guidelines.
      The frequency of extended spectrum betalactamases (ESBL) or metallo
      betalactamases (MBL)-producing isolates, patient demographics, and the
      susceptibility to various antimicrobial agents were described. BlaCTX-M was the
      most frequently detected betalactamase in all isolates. Moreover, MBL producing
      K. pneumoniae carried blaIMP and blaVIM at 100 and 41.6%, respectively but no MBL
      positive E. coli was detected. Class 1 integrons were more frequent among E. coli
      and K. pneumoniae isolates in comparison with class 2 integrons and the frequency
      of intI2 in K. pneumoniae was significantly higher than E. coli isolates. Five
      different resistance gene arrays were identified among class 1 integrons.
      Dihydrofolate reductase (dfrA) and aminoglycoside adenyltransferase (aad) gene
      cassettes were found to be predominant in the class 1 integrons. These results
      indicate that class 1 integrons are widespread among ESBL-producing isolates of
      K. pneumoniae and E. coli and appropriate surveillance and control measures are
      essential to prevent further dissemination of these elements among
      Enterobacteriaceae in our country. 

PMID- 24571250
TI  - Genetic architecture of skeletal evolution in European lake and stream
      stickleback.
AB  - Advances in genomic techniques are greatly facilitating the study of molecular
      signatures of selection in diverging natural populations. Connecting these
      signatures to phenotypes under selection remains challenging, but benefits from
      dissections of the genetic architecture of adaptive divergence. We here perform
      quantitative trait locus (QTL) mapping using 488 F2 individuals and 2011 single
      nucleotide polymorphisms (SNPs) to explore the genetic architecture of skeletal
      divergence in a lake-stream stickleback system from Central Europe. We find QTLs
      for gill raker, snout, and head length, vertebral number, and the extent of
      lateral plating (plate number and height). Although two large-effect loci emerge,
      QTL effect sizes are generally small. Examining the neighborhood of the QTL
      linked SNPs identifies several genes involved in bone formation, which emerge as
      strong candidate genes for skeletal evolution. Finally, we use SNP data from the
      natural source populations to demonstrate that some SNPs linked to QTLs in our
      cross also exhibit striking allele frequency differences in the wild, suggesting
      a causal role of these QTLs in adaptive population divergence. Our study paves
      the way for comparative analyses across other (lake-stream) stickleback
      populations, and for functional investigations of the candidate genes. 

PMID- 24571249
TI  - Protective effects of melatonin in reducing oxidative stress and in preserving
      the fluidity of biological membranes: a review.
AB  - Free radicals generated within subcellular compartments damage macromolecules
      which lead to severe structural changes and functional alterations of cellular
      organelles. A manifestation of free radical injury to biological membranes is the
      process of lipid peroxidation, an autooxidative chain reaction in which
      polyunsaturated fatty acids in the membrane are the substrate. There is
      considerable evidence that damage to polyunsaturated fatty acids tends to reduce
      membrane fluidity. However, adequate levels of fluidity are essential for the
      proper functioning of biological membranes. Thus, there is considerable interest
      in antioxidant molecules which are able to stabilize membranes because of their
      protective effects against lipid peroxidation. Melatonin is an indoleamine that
      modulates a wide variety of endocrine, neural and immune functions. Over the last
      two decades, intensive research has proven this molecule, as well as its
      metabolites, to possess substantial antioxidant activity. In addition to their
      ability to scavenge several reactive oxygen and nitrogen species, melatonin
      increases the activity of the glutathione redox enzymes, that is, glutathione
      peroxidase and reductase, as well as other antioxidant enzymes. These beneficial
      effects of melatonin are more significant because of its small molecular size and
      its amphipathic behaviour, which facilitates ease of melatonin penetration into
      every subcellular compartment. In the present work, we review the current
      information related to the beneficial effects of melatonin in maintaining the
      fluidity of biological membranes against free radical attack, and further, we
      discuss its implications for ageing and disease. 

PMID- 24571251
TI  - Lithium toxicity and PRES: a novel association.
AB  - We report two cases of posterior reversible encephalopathy syndrome (PRES)
      occurring in association with supra-therapeutic serum lithium levels. Although
      the neurologic manifestations of lithium toxicity are well known, this is, to our
      knowledge, the first report describing a link between lithium toxicity and PRES.
      We discuss the current understanding of the pathogenesis of PRES and suggest
      mechanisms by which lithium may play a role in its development.

PMID- 24571252
TI  - Evaluation of deterrent impact of Ontario's Street Racing and Stunt Driving Law
      on extreme speeding convictions.
AB  - OBJECTIVE: The purpose of this study was to conduct a process and outcome
      evaluation of the deterrent impact of Ontario's street racing and stunt driving
      legislation, introduced in September 2007, on extreme speeding convictions. It
      was hypothesized that because males are much more likely to engage in speeding,
      street racing, and stunt driving, the new law would have more impact in reducing
      extreme speeding in males compared to females. METHODS: Descriptive statistics
      and time series plots were used for the suspensions data. Interrupted time series
      analysis with autoregressive integrated moving average (ARIMA) modeling was
      applied to the monthly extreme speeding convictions in Ontario for the period of
      January 1, 2003, to December 31, 2011, to assess the impact of the new
      legislation, separately for male drivers (intervention group) and female drivers
      (comparison group). RESULTS: The results indicated that per licensed driver, 1.21
      percent of 16- to 24-year-old male drivers and 0.37 percent of 25- to 64-year-old
      male drivers had their licenses suspended between September 2007 and December
      2011. This is in contrast to female drivers: 0.21 percent of 16- to 24-year-old
      female drivers and 0.07 percent of 25- to 64-year-old female drivers had their
      licenses suspended during the same time period. A significant intervention effect
      of reduced extreme speeding convictions was found in the male driver group,
      though no corresponding effect was observed in the female driver group. The
      findings of this study are consistent with previous research on demographics of
      street racers and stunt drivers. CONCLUSIONS: These findings are congruent with
      deterrence theory that certain, swift, and severe sanctions can deter risky
      driving behavior and support the hypothesis that legal sanctions can have an
      impact on the extreme speeding convictions of the intervention group.

PMID- 24571253
TI  - Effects of genetic, processing, or product formulation changes on efficacy and
      safety of probiotics.
AB  - Commercial probiotic strains for food or supplement use can be altered in
      different ways for a variety of purposes. Production conditions for the strain or
      final product may be changed to address probiotic yield, functionality, or
      stability. Final food products may be modified to improve flavor and other
      sensory properties, provide new product formats, or respond to market
      opportunities. Such changes can alter the expression of physiological traits
      owing to the live nature of probiotics. In addition, genetic approaches may be
      used to improve strain attributes. This review explores whether genetic or
      phenotypic changes, by accident or design, might affect the efficacy or safety of
      commercial probiotics. We highlight key issues important to determining the need
      to re-confirm efficacy or safety after strain improvement, process optimization,
      or product formulation changes. Research pinpointing the mechanisms of action for
      probiotic function and the development of assays to measure them are greatly
      needed to better understand if such changes have a substantive impact on
      probiotic efficacy. 

PMID- 24571254
TI  - Probiotics and prebiotics: prospects for public health and nutritional
      recommendations.
AB  - Probiotics and prebiotics are useful interventions for improving human health
      through direct or indirect effects on the colonizing microbiota. However,
      translation of these research findings into nutritional recommendations and
      public health policy endorsements has not been achieved in a manner consistent
      with the strength of the evidence. More progress has been made with clinical
      recommendations. Conclusions include that beneficial cultures, including
      probiotics and live cultures in fermented foods, can contribute towards the
      health of the general population; prebiotics, in part due to their function as a
      special type of soluble fiber, can contribute to the health of the general
      population; and a number of challenges must be addressed in order to fully
      realize probiotic and prebiotic benefits, including the need for greater
      awareness of the accumulated evidence on probiotics and prebiotics among policy
      makers, strategies to cope with regulatory roadblocks to research, and high
      quality human trials that address outstanding research questions in the field. 

PMID- 24571255
TI  - Targeting epigenetic regulators for cancer therapy.
AB  - Human gene expression patterns are controlled and coordinated by the activity of
      a diverse array of epigenetic regulators, including histone methyltransferases,
      acetyltransferases, and chromatin remodelers. Deregulation of these epigenetic
      pathways can lead to genome-wide changes in gene expression, with serious disease
      consequences. In recent years, research has suggested that cross talk between
      genomic (i.e., for example, mutations, translocations) and epigenomic factors may
      drive the etiology of both hematologic malignancies and solid tumors. Current
      work in translational research seeks to identify epigenetic regulators whose
      aberrant activity contributes to oncogenesis, including the histone
      methyltransferases DOT1L and EZH2 and the bromodomain-containing BET family, and
      to develop drugs that inhibit the aberrant activity of these regulators.
      Preclinical and clinical studies using small-molecule inhibitors of epigenetic
      regulators have underscored their value for therapeutic intervention, and these
      inhibitors can also be used to drive further studies into dissecting the
      functions of epigenetic factors in normal and cancer cells. 

PMID- 24571256
TI  - Precis of nutrition of children and women in Haiti: analyses of data from 1995 to
      2012.
AB  - Between 1995 and 2012, many surveys including child and maternal nutrition
      indicators were conducted in Haiti. While many questions emerged from the results
      of those surveys, they have remained unanswered, in particular as they pertain to
      the determinants of poor children's and women's nutrition in Haiti. The purpose
      of this paper is to fill that gap and provide policymakers, program managers, and
      readers interested in nutrition issues in Haiti with information on (1) the
      trends and determinants of infant and young child feeding and food practices; (2)
      micronutrient deficiencies among children and women; (3) the status of severe
      acute malnutrition in children; (4) associations among women's empowerment,
      access to health care, water, and sanitation and child nutrition; (5) the current
      community-based early child care and nutrition initiatives; and (6) the status of
      nutrition governance in the country. By looking at many sources of data,
      including previously published and new data, we provide insight into major
      predictors of child malnutrition and associations among child feeding practices,
      maternal nutrition, and child growth outcomes. We also show that important
      progress has been made recently in the governance of nutrition programs and in
      child and maternal nutrition indicators, a result of effective evidence-based
      advocacy, partnerships, and design, implementation, and scale-up of nutrition
      specific and sensitive interventions. 

PMID- 24571257
TI  - Zirconium(IV) metallocavitands as blue-emitting materials.
AB  - A series of zirconium-carboxylate metallocavitands with the general formula
      [(CpZr)3(MU-kappa2,O',O"CR)3(MU3-O)(MU2-OH)3]Cl (Cp = cyclopentadienyl; R = C5H4N
      (5), C6H7N (6), C18H14N (7), and C18H12N (8)) were synthesized in moderate to
      high yields (40-83%) by reacting the corresponding carboxylic acids 1-4 with
      Cp2ZrCl2 in a self-assembly procedure at room temperature. The metallocavitands
      were characterized using (1)H and (13)C NMR spectroscopy and by single-crystal X
      ray diffraction. Complexes 7 and 8 exhibit efficient photoluminescence properties
      in solution. The photoluminescence peak of 7 was observed at 464 nm and that of 8
      at 422 nm with respective quantum yields in solution of 87 and 65%. 

PMID- 24571258
TI  - Lactoferrin gene knockdown leads to similar effects to iron chelation in human
      adipocytes.
AB  - In human and mice adipose tissue, lactoferrin (LTF) has been found to be
      associated with increased adipogenesis and decreased inflammatory markers. Here,
      we aimed to investigate the effects of LTF knockdown (KD) in human adipocyte
      differentiation. In addition, the effects of exogenous LTF administration and
      iron chelation [using deferoxamine (DFO, 10 MUM)] were tested. In both
      subcutaneous and visceral pre-adipocytes, LTF KD led to decrease significantly
      adipogenic, lipogenic and insulin signalling-related gene expression and a
      significant increase in the gene expression of inflammatory mediators. Human
      lactoferrin (hLf, 1 MUM) administration led to recover adipocyte differentiation
      in LTF KD pre-adipocytes. Interestingly, iron chelation triggered similar effects
      to LTF KD, decreasing significantly adipogenic gene expressions. Of note, DFO (10
      MUM) and hLf (1 and 10 MUM) co-administration led to a dose-dependent recovery of
      adipocyte differentiation. These new data reveal that endogenous LTF biosynthesis
      during human adipocyte differentiation is essential to achieve this process,
      possibly, modulating adipocyte iron homoeostasis. hLf administration might be a
      useful therapeutic target in obesity-associated adipose tissue dysfunction.

PMID- 24571260
TI  - Editorial comment to simple and reliable predictor of urinary continence after
      radical prostatectomy: serial measurement of urine loss ratio after catheter
      removal.

PMID- 24571259
TI  - LMO2 and BCL6 are associated with improved survival in primary central nervous
      system lymphoma.
AB  - Primary central nervous system lymphoma (PCNSL) is an aggressive sub-variant of
      non-Hodgkin lymphoma (NHL) with morphological similarities to diffuse large B
      cell lymphoma (DLBCL). While methotrexate (MTX)-based therapies have improved
      patient survival, the disease remains incurable in most cases and its
      pathogenesis is poorly understood. We evaluated 69 cases of PCNSL for the
      expression of HGAL (also known as GCSAM), LMO2 and BCL6 - genes associated with
      DLBCL prognosis and pathobiology, and analysed their correlation to survival in
      49 PCNSL patients receiving MTX-based therapy. We demonstrate that PCNSL
      expresses LMO2, HGAL(also known as GCSAM) and BCL6 proteins in 52%, 65% and 56%
      of tumours, respectively. BCL6 protein expression was associated with longer
      progression-free survival (P = 0.006) and overall survival (OS, P = 0.05), while
      expression of LMO2 protein was associated with longer OS (P = 0.027). Further
      research is needed to elucidate the function of BCL6 and LMO2 in PCNSL. 

PMID- 24571261
TI  - Comparison of external radiotherapy and percutaneous vertebroplasty for spinal
      metastasis.
AB  - AIM: To compare the efficacy of external radiotherapy (ERT) and percutaneous
      vertebroplasty (PVP) for spinal metastasis. METHODS: A total of 137 patients with
      174 spinal metastases between June 2006 and April 2009 in our hospital were
      reviewed. For their spinal metastasis, 52 patients received ERT; 46 patients
      received PVP; and 39 patients received both ERT and PVP. Pain and neurological
      deficit response, overall survival, and side effects were evaluated. RESULTS: ERT
      combined with PVP achieved pain remission in 84.8% of the patients, which was
      higher than ERT (72.5%) or PVP (76.3%) alone. It also showed a higher remission
      rate of neurological deficits (50%) than ERT (18.2%) or PVP (11.1%) alone.
      Toxicities from the employed treatments were mild. The Karnofsky Performance
      Score and visceral or brain metastases were the significant influencing factors
      for overall survival. Patients with spinal metastases derived from breast cancer
      had a significantly better overall survival than those whose spinal metastases
      were derived from lung cancer. CONCLUSION: ERT combined with PVP can be a more
      effective treatment for spinal metastases; however, prospective randomized trials
      are needed to draw any definitive conclusion.

PMID- 24571262
TI  - Combined analysis of polycation/ODN polyplexes by analytical ultracentrifugation
      and dynamic light scattering reveals their size, refractive index increment,
      stoichiometry, porosity, and molecular weight.
AB  - Analytical ultracentrifugation (AUC) and dynamic light scattering (DLS) were
      combined to characterize polyplexes formed with 10 kDa chitosan or 10 kDa PEI and
      oligodeoxynucleotides (ODN). Combined analysis revealed that both polyplexes were
      highly porous (over 80%) and that their weight average hydrodynamic diameters
      were of 46 and 55 nm for chitosan/ODN and PEI/ODN complexes, respectively.
      Transformation of the sedimentation coefficient distribution to a size and
      molecular weight distribution gave an average molecular weight of 19 and 29 MDa
      for chitosan and PEI polyplexes, respectively. Data from AUC also allowed for the
      calculation of the actual dn/dc and N/P ratios of each polyplex. Additional data
      from scanning electron microscopy and static light scattering confirmed the
      conclusions that were initially derived from AUC and DLS, thus validating that
      the combination of AUC and DLS is a powerful approach to characterize polyplexes
      in terms of refractive index increment, size, and molecular weight distributions,
      as well as porosity. 

PMID- 24571263
TI  - Protein adsorption into mesopores: a combination of electrostatic interaction,
      counterion release, and van der Waals forces.
AB  - Bovine heart cytochrome c has been immobilized into the mesoporous silica host
      material SBA-15 in both its native folded and urea-unfolded state. The comparison
      of the two folding states' behavior casts doubt on the commonly used explanation
      of cytochrome c adsorption, that is, the electrostatic interaction model. A
      detailed investigation of the protein binding as a function of pH and ionic
      strength of the buffer solution reveals the complex nature of the protein-silica
      interaction. Electrostatic interaction, van der Waals forces, and entropic
      contributions by counterion release each contribute to adsorption on the silica
      pore walls. 

PMID- 24571267
TI  - Assessing lesbian, gay, and bisexual affirmative training in couple and family
      therapy: establishing the validity of the Faculty Version of the Affirmative
      Training Inventory.
AB  - This study established the validity and factor structure of the Faculty Version
      of the Affirmative Training Inventory (ATI-F), which assesses faculty members'
      perceptions of the level of lesbian, gay, and bisexual (LGB) affirmative training
      that occurs in clinical programs. Additionally, this study examined the latent
      associations among the subscales of the ATI-F and three convergent validity items
      utilizing a sample of 117 faculty members from accredited family therapy
      programs. The findings provide empirical support for the relationship between
      including classroom content on LGB affirmative therapy and faculty members'
      beliefs about LGB individuals and relationships. Specifically, faculty members
      who report more positive beliefs about LGB clients appear to be more likely to
      include LGB affirmative therapy content in the courses they teach. 

PMID- 24571268
TI  - Knee surgery recovery: Post-operative Quality of Recovery Scale comparison of age
      and complexity of surgery.
AB  - BACKGROUND: Initial validation and feasibility for the Post-operative Quality of
      Recovery Scale (PQRS) was published in 2010. Ongoing validation includes studies
      to determine whether this scale can discriminate differences in recovery between
      cohorts. METHODS: A prospective cohort study included 61 patients, 18-40 years,
      and 61 patients, aged >= 65 years, undergoing knee arthroscopy under general
      anaesthesia; and 13 patients, aged >= 65 years, undergoing total knee replacement
      under general anaesthesia. Patients were assessed using the PQRS. Assessments
      were performed pre-surgery, at 15 and 40 min, 1 and 3 days, and 3 months after
      surgery. RESULTS: The effect of age was assessed by comparing young versus older
      arthroscopy patients. There were minimal differences in recovery profiles, other
      than for the nociceptive domain, where pain recovery was significantly better in
      the older arthroscopy patients (P < 0.001). The effect of surgery was assessed by
      comparing older patients undergoing knee arthroscopy with knee replacement
      patients. Recovery was significantly worse for the knee replacement group for
      cognition (P = 0.015), nociception (pain and nausea, P < 0.001), activities of
      daily living (P < 0.001), emotive recovery (P = 0.029), and all-domains recovery
      (P < 0.001). Despite differences in quality of recovery, satisfaction was high in
      all cohorts. CONCLUSIONS: Knee replacement had a large effect on recovery
      compared with knee arthroscopy. Age had minimal effect on recovery after knee
      arthroscopy. The study showed the ability of the PQRS to discriminate recovery in
      different domains.

PMID- 24571269
TI  - Conserved histidine of metal transporter AtNRAMP1 is crucial for optimal plant
      growth under manganese deficiency at chilling temperatures.
AB  - Manganese (Mn) is an essential nutrient required for plant growth, in particular
      in the process of photosynthesis. Plant performance is influenced by various
      environmental stresses including contrasting temperatures, light or nutrient
      deficiencies. The molecular responses of plants exposed to such stress factors in
      combination are largely unknown. Screening of 108 Arabidopsis thaliana
      (Arabidopsis) accessions for reduced photosynthetic performance at chilling
      temperatures was performed and one accession (Hog) was isolated. Using genetic
      and molecular approaches, the molecular basis of this particular response to
      temperature (G * E interaction) was identified. Hog showed an induction of a
      severe leaf chlorosis and impaired growth after transfer to lower temperatures.
      We demonstrated that this response was dependent on the nutrient content of the
      soil. Genetic mapping and complementation identified NRAMP1 as the causal gene.
      Chlorotic phenotype was associated with a histidine to tyrosine (H239Y)
      substitution in the allele of Hog NRAMP1. This led to lethality when Hog
      seedlings were directly grown at 4 degrees C. Chemical complementation and
      hydroponic culture experiments showed that Mn deficiency was the major cause of
      this G * E interaction. For the first time, the NRAMP-specific highly conserved
      histidine was shown to be crucial for plant performance.

PMID- 24571270
TI  - An increase in melatonin in transgenic rice causes pleiotropic phenotypes,
      including enhanced seedling growth, delayed flowering, and low grain yield.
AB  - No previous reports have described the effects of an increase in endogenous
      melatonin levels on plant yield and reproduction. Here, the phenotypes of
      melatonin-rich transgenic rice plants overexpressing sheep serotonin N
      acetyltransferase were investigated under field conditions. Early seedling growth
      of melatonin-rich transgenic rice was greatly accelerated, with enhanced biomass
      relative to the wild type (WT). However, flowering was delayed by 1 wk in the
      transgenic lines compared with the WT. Grain yields of the melatonin-rich
      transgenic lines were reduced by 33% on average. Other phenotypes also varied
      among the transgenic lines. For example, the transgenic line S1 exhibited greater
      height and biomass than the WT, while the S10 transgenic line showed diminished
      height and an increase in panicle numbers per plant. The expression levels of
      Oryza sativa homeobox1 (OSH1) and TEOSINTE BRANCHED1 (TB1) genes, two key
      regulators of meristem initiation and maintenance, were not altered in the
      transgenic lines. These data demonstrate that an alteration of endogenous
      melatonin levels leads to pleiotropic effects such as height, biomass, panicle
      number, flowering time, and grain yield, indicating that melatonin behaves as a
      signaling molecule in plant growth and reproduction.

PMID- 24571271
TI  - Novel synthesis of 3-substituted 2,3-dihydrobenzofurans via ortho-quinone methide
      intermediates generated in situ.
AB  - A new method is presented for the regioselective one-pot synthesis of 3
      substituted 2,3-dihydrobenzofurans from 2-bromo-1-{2
      [(triisopropylsilyl)oxy]phenyl}ethyl nitrate by fluoride-induced desilylation
      leading to o-quinone methide generation, Michael addition of different C, N, O,
      and S nucleophiles, and intramolecular 5-exo-tet elimination of a bromide anion.
      The method has potential synthetic applications in drug discovery. 

PMID- 24571272
TI  - Theoretical study of the hydroxyl radical addition to uracil and photochemistry
      of the formed U6OH* adduct.
AB  - Hydroxyl radical ((*)OH) is produced in biological systems by external or
      endogenous agents. It can damage DNA/RNA by attacking pyrimidine nucleobases
      through the addition to the C5?C6 double bond. The adduct resulting from the
      attachment at the C5 position prevails in the experimental measurements, although
      the reasons for this preference remain unclear. The first aim of this work is
      therefore to shed light on the comprehension of this important process. Thus, the
      thermal (*)OH addition to the C5?C6 double bond of uracil has been studied
      theoretically by using DFT, MP2, and the multiconfigurational CASPT2//CASSCF
      methodologies. The in-vacuo results obtained with the latter protocol plus the
      analysis of solvent effects support the experimental observation. A significant
      lower barrier height is predicted for the C5 pathway with respect to that of the
      C6 route. In contrast to the C5 adduct, the C6 adduct is able to absorb visible
      light. Hence, the second aim of the work is to study the photochemistry of this
      species using the CASPT2//CASSCF methodology within the framework of the
      photochemical reaction path approach (PRPA). The nonradiative decay to the ground
      state of this compound has been characterized. A photoreactive character is
      predicted for the C6 adduct in the excited states according to the presence of
      excited-state minima along the main decay channel. Finally, a new mechanism of
      photodissociation has been explored, which implies the photoinduced regeneration
      of the canonical nucleobase by irradiating with visible light, being therefore
      relevant in RNA protection against damage by reactive oxygen species. 

PMID- 24571273
TI  - Spiromastixones A-O, antibacterial chlorodepsidones from a deep-sea-derived
      Spiromastix sp. fungus.
AB  - Fifteen new depsidone-based analogues named spiromastixones A-O (1-15) were
      isolated from the fermentation broth of a deep-sea Spiromastix sp. fungus. Their
      structures were elucidated on the basis of extensive NMR and mass spectroscopic
      analysis in association with chemical conversion. Spiromastixones A-O are
      classified into two subtypes based on the orientation of ring C relative to ring
      A, while the n-propyl substituents on rings A and C are rarely seen in natural
      products. Most analogues are substituted by various numbers of chlorine atoms.
      All compounds exhibited significant inhibition against Gram-positive bacteria
      including Staphylococcus aureus, Bacillus thuringiensis, and Bacillus subtilis
      with MIC values ranging from 0.125 to 8.0 MUg/mL. In addition, compounds 6-10
      displayed potent inhibitory effects against methicillin-resistant bacterial
      strains of S. aureus (MRSA) and S. epidermidis (MRSE), while 10 also inhibited
      the growth of the vancomycin-resistant bacteria Enterococcus faecalis and E.
      faecium (VRE). The structure-activity relationships are discussed. 

PMID- 24571274
TI  - The accuracy of ultrasound-estimated fetal weight in extremely preterm infants: a
      comparison of small for gestational age and appropriate for gestational age.
AB  - OBJECTIVES: To compare the accuracy of estimated fetal weight (EFW) in extremely
      preterm small for gestational age (SGA) and appropriate for gestational age (AGA)
      infants and report other significant factors influencing the accuracy of EFW.
      METHODS: A retrospective cohort study of singleton pregnancies 22(+0) -27(+6) 
      weeks. Women were included in the study if an ultrasound scan had been performed
      within seven days of delivery, with no major fetal anomaly and data available to
      calculate customised birthweight (BW) centiles. Mean error of EFW and actual BW
      and mean % error of EFW and actual birthweight were compared for SGA and AGA
      infants. A stepwise backward elimination linear regression model was used to
      determine the significant factors influencing the accuracy of EFW. RESULTS: A
      total of 134 cases (51 SGA and 83 AGA) were analysed. The mean gestational age at
      delivery was 25(+2)  weeks (SD 11.5 days) and mean BW 711 g (SD 227 g). Overall
      mean percentage error of EFW and actual BW was 8.8% (range 0-34.6%). There was a
      significant difference in mean error of EFW and actual BW for SGA and AGA
      deliveries (mean +16 g versus -23 g, respectively, P = 0.01) and in mean % error
      of EFW (11.2%, 95%CI 9.1-13.3 versus 7.4%, 95% CI 6.2-8.6 P = 0.009). Factors
      that significantly influenced the accuracy of EFW included SGA (P = 0.001, coeff.
      = -3.73, 95% CI -5.94/-1.52), scan to delivery interval (P = 0.02, coeff. = 0.66,
      95% CI 0.12/1.21) and reduced amniotic fluid (P = 0.008, coeff = 3.61, 95% CI 
      5.47/-0.85). CONCLUSIONS: Ultrasonographic EFW for extreme preterm SGA fetuses is
      less accurate than AGA fetuses and is more likely to overestimate EFW. This
      should be considered when counselling women with growth restricted fetuses at the
      limits of viability.

PMID- 24571276
TI  - Direct dynamics simulation of the activation and dissociation of 1,5
      dinitrobiuret (HDNB).
AB  - Certain room-temperature ionic liquids exhibit hypergolic activity as liquid
      bipropellants. Understanding the chemical pathways and reaction mechanisms
      associated with hypergolic ignition is important for designing new fuels. It has
      been proposed (J. Phys. Chem. A 2008, 112, 7816) that an important ignition step
      for the hypergolic ionic liquid bipropellant system of dicyanamide/nitric acid is
      the activation and dissociation of the 1,5-dinitrobiuret anion DNB(-). For the
      work reported here, a quasiclassical direct dynamics simulation, at the DFT/M05
      2X level of theory, was performed to model H(+) + DNB(-) association and the
      ensuing unimolecular decomposition of HDNB. This association step is 324 kcal/mol
      exothermic, and the most probable collision event is for H(+) to directly scatter
      off of DNB(-), without sufficient energy transfer to DNB(-) for H(+) to associate
      and form a highly vibrationally excited HDNB molecule. Approximately 1/3 of the
      trajectories do form HDNB, which decomposes by eight different reaction paths and
      whose unimolecular dynamics is highly nonstatistical. Some of these paths are the
      same as those found in a direct dynamics simulation of the high-temperature
      thermal decomposition of HDNB (J. Phys. Chem. A 2011, 115, 8064), for a similar
      total energy.

PMID- 24571275
TI  - Family medicine model in Turkey: a qualitative assessment from the perspectives
      of primary care workers.
AB  - BACKGROUND: A person-list-based family medicine model was introduced in Turkey
      during health care reforms. This study aimed to explore from primary care
      workers' perspectives whether this model could achieve the cardinal functions of
      primary care and have an integrative position in the health care system. METHODS:
      Four groups of primary care workers were included in this exploratory-descriptive
      study. The first two groups were family physicians (FP) (n = 51) and their
      ancillary personnel (n = 22). The other two groups were physicians (n = 44) and
      midwives/nurses (n = 11) working in community health centres. Participants were
      selected for maximum variation and 102 in-depth interviews and six focus groups
      were conducted using a semi-structured form. RESULTS: Data analysis yielded five
      themes: accessibility, first-contact care, longitudinality, comprehensiveness,
      and coordination. Most participants stated that many people are not registered
      with any FP and that the majority of these belong to the most disadvantaged
      groups in society. FPs reported that 40-60% of patients on their lists have never
      received a service from them and the majority of those who use their services do
      not use FPs as the first point of contact. According to most participants, the
      list-based system improved the longitudinality of the relationship between FPs
      and patients. However, based on other statements, this improvement only applies
      to one quarter of the population. Whereas there was an improvement limited to a
      quantitative increase in services (immunisation, monitoring of pregnant women and
      infants) included in the performance-based contracting system, participants
      stated that services not among the performance targets, such as family planning,
      postpartum follow-ups, and chronic disease management, could be neglected. FPs
      admitted not being able to keep informed of services their patients had received
      at other health institutions. Half of the participants stated that the list-based
      system removed the possibility of evaluating the community as a whole.
      CONCLUSIONS: According to our findings, FPs have a limited role as the first
      point of contact and in giving longitudinal, comprehensive, and coordinated care.
      The family medicine model in Turkey is unable to provide a suitable structure to
      integrate health care services.

PMID- 24571277
TI  - Creative surrender: a Milnerian view of works by Y. Z. Kami.
AB  - Born in 1900, Marion Milner started psychoanalytic training in 1940, following a
      trajectory which took her into territory later developed by Winnicott. She was an
      independent thinker who drew on a variety of sources to explore her own and her
      patients' creativity. She linked the creative process to psychic health and to
      the ability to achieve a level of perception that leads not to the re-creation of
      lost objects but to the creation of what did not exist before. By linking
      Milner's theory of perception to works by Y.Z. Kami, I draw parallels between a
      psychoanalyst's perception of the creative process and that process as described
      and executed by an artist. Milner's lens and Kami's brush both articulate
      thoughts and feelings about what it means to be human, the condition of mortality
      and, after Freud, the illusions that sustain mankind through the creation of the
      gods. This study looks at how the work of an artist and a psychoanalytic thinker
      can be mutually reinforcing and inter-animating, thereby broadening and deepening
      the insights gained from both. 

PMID- 24571279
TI  - White matter alterations in bipolar disorder: potential for drug discovery and
      development.
AB  - OBJECTIVES: Brain white matter (WM) alterations have recently emerged as
      potentially relevant in bipolar disorder. New techniques such as diffusion tensor
      imaging allow precise exploration of these WM microstructural alterations in
      bipolar disorder. Our objective was to critically review WM alterations in
      bipolar disorder, using neuroimaging and neuropathological studies, in the
      context of neural models and the potential for drug discovery and development.
      METHODS: We conducted a systematic PubMed and Google Scholar search of the WM and
      bipolar disorder literature up to and including January 2013. RESULTS: Findings
      relating to WM alterations are consistent in neuroimaging and neuropathology
      studies of bipolar disorder, especially in regions involved in emotional
      processing such as the anterior frontal lobe, corpus callosum, cingulate cortex,
      and in fronto-limbic connections. Some of the structural alterations are related
      to genetic risk factors for bipolar disorder and may underlie the dysfunctional
      emotional processing described in recent neurobiological models of bipolar
      disorder. Medication effects in bipolar disorder, from lithium and other mood
      stabilizers, might impact myelinating processes, particularly by inhibition of
      glycogen synthase kinase-3 beta. CONCLUSIONS: Pathways leading to WM alterations
      in bipolar disorder represent potential targets for the development and discovery
      of new drugs. Myelin damage in bipolar disorder suggests that the effects of
      existing pro-myelinating drugs should also be evaluated to improve our
      understanding and treatment of this disease.

PMID- 24571280
TI  - A new water oxidation catalyst: lithium manganese pyrophosphate with tunable Mn
      valency.
AB  - The development of a water oxidation catalyst has been a demanding challenge for
      the realization of overall water-splitting systems. Although intensive studies
      have explored the role of Mn element in water oxidation catalysis, it has been
      difficult to understand whether the catalytic capability originates mainly from
      either the Mn arrangement or the Mn valency. In this study, to decouple these two
      factors and to investigate the role of Mn valency on catalysis, we selected a new
      pyrophosphate-based Mn compound (Li2MnP2O7), which has not been utilized for
      water oxidation catalysis to date, as a model system. Due to the monophasic
      behavior of Li2MnP2O7 with delithiation, the Mn valency of Li(2-x)MnP2O7 (x =
      0.3, 0.5, 1) can be controlled with negligible change in the crystal framework
      (e.g., volume change ~1%). Moreover, inductively coupled plasma mass
      spectrometry, X-ray photoelectron spectroscopy, ex-situ X-ray absorption near
      edge structure, galvanostatic charging-discharging, and cyclic voltammetry
      analysis indicate that Li(2-x)MnP2O7 (x = 0.3, 0.5, 1) exhibits high catalytic
      stability without additional delithiation or phase transformation. Notably, we
      observed that, as the averaged oxidation state of Mn in Li(2-x)MnP2O7 increases
      from 2 to 3, the catalytic performance is enhanced in the series Li2MnP2O7 <
      Li(1.7)MnP2O7 < Li(1.5)MnP2O7 < LiMnP2O7. Moreover, Li2MnP2O7 itself exhibits
      superior catalytic performance compared with MnO or MnO2. Our study provides
      valuable guidelines for developing an efficient Mn-based catalyst under neutral
      conditions with controlled Mn valency and atomic arrangement.

PMID- 24571278
TI  - Dietary essential oils improve the hepatic antioxidative status of broiler
      chickens.
AB  - 1. A total of 200 male Ross 308 chickens were used to evaluate the effects of a
      standardised combination of essential oils including 5% carvacrol, 3%
      cinnamaldehyde and 2% capsicum oleoresin (XT 6930; Pancosma S.A., Geneva,
      Switzerland) on their performance, hepatic antioxidant concentration and caecal
      tonsils morphometry. 2. Two diets were offered to broiler chickens from d old to
      21 d of age. The control diet (C) was slightly lower in metabolisable energy
      (12.13 MJ/kg ME) and crude protein (215 g/kg CP) than breeders' recommendation.
      The second diet, made as XT 6930, was added on the top of the control diet at 100
      mg/kg. Each diet was offered ad libitum to birds housed in one of 10 floor pens
      in a randomised complete block design. The birds were housed in 20 floor pens, 10
      birds in each pen, and were allocated to 10 replicates of the two dietary
      treatments. 3. The concentration of antioxidants in the liver of the birds was
      determined using high-performance liquid chromatography (HPLC) at 21 d of age.
      Birds fed control diet only had lower weight and converted less efficiently feed
      to gain compared to birds fed essential oils-supplemented diet. Feed consumption
      was not affected by dietary treatments. The antioxidant data showed that
      supplemented essential oils improved the hepatic concentration of carotenoids and
      coenzyme Q10 when fed to broiler chickens. The morphometry of the caecal tonsils
      of the birds was not influenced by dietary treatments. 4. It can be concluded
      that that dietary combination of essential oils, including carvacrol,
      cinnamaldehyde and capsicum oleoresin, improved growth, feed efficiency and the
      hepatic concentration of carotenoids and coenzyme Q10 when fed to broiler
      chickens.

PMID- 24571281
TI  - Association of type of renal surgery and access to robotic technology for kidney
      cancer: results from a population-based cohort.
AB  - OBJECTIVE: To evaluate the relationship between partial nephrectomy (PN) and
      hospital availability of robot-assisted surgery from a population-based cohort in
      the USA. METHODS: After merging the Nationwide Inpatient Sample (NIS) and the
      American Hospital Association survey from 2006 to 2008, we identified 21 179
      patients who underwent either PN or radical nephrectomy (RN) for renal cell
      carcinoma (RCC). The primary outcome assessed was the type of nephrectomy
      performed. Multivariable logistic regression identified the patient and hospital
      characteristics associated with receipt of PN. RESULTS: We identified 4832
      (22.8%) and 16 347 (77.2%) patients who were treated for RCC with PN and RN,
      respectively. On multivariable analysis, patients were more likely to receive PN
      at academic centres (odds ratio [OR] 2.77; P < 0.001), urban centres (OR 3.66; P
      < 0.001) and American College of Surgeons (ACOS)-designated cancer centres (OR:
      1.10; P < 0.05) compared with non-academic, rural and non-ACOS-designated cancer
      centre hospitals, respectively. Robot-assisted surgery availability at a hospital
      was also associated with a higher adjusted odds of PN compared with centres
      without that availability (OR 1.28; P < 0.001). CONCLUSIONS: Although academic
      and urban locations are established factors that affect the receipt of PN for
      RCC, the availability of robot-assisted surgery at a hospital was also
      independently associated with higher use of PN. Our results are informative in
      identifying other key hospital characteristics which may facilitate greater
      adoption of PN.

PMID- 24571282
TI  - The influence of oral contraceptive knowledge on oral contraceptive continuation
      among young women.
AB  - BACKGROUND: Using a multidimensional approach, we assessed young women's
      knowledge of oral contraceptives (OC) and its influence on OC continuation rates.
      METHODS: We used data from 659 women aged 13-25 years participating in a
      randomized controlled trial of an educational text message OC continuation
      intervention. Women received 6 months of daily text messages or routine care. At
      baseline and 6 months, we administered a comprehensive 41-item questionnaire
      measuring knowledge of OC's mechanism, effectiveness, use, side effects, risks,
      and benefits. We ascertained OC continuation status and reasons for
      discontinuation at 6 months. We analyzed relationships between OC knowledge and
      continuation with multivariable logistic regression. RESULTS: Young women scored,
      on average, 22.8 out of 41 points on the OC knowledge assessment at baseline and
      24.7 points at 6 months. The 6-month OC continuation rate was 59%. OC continuers
      had >2-points-higher OC knowledge scores at 6 months than discontinuers
      (p<0.001). Those who reported discontinuing their OCs for side effects and
      forgetfulness scored >2 points lower than women who discontinued for other
      reasons (p-values<0.001). In multivariable regression models, each correct
      response on the baseline and 6-month knowledge assessments was associated with a
      4% and 6% increased odds of OC continuation, respectively. Six-month OC knowledge
      scores were negatively associated with OC discontinuation due to side effects
      (odds ratio [OR] 0.94) and forgetfulness (OR 0.88). CONCLUSIONS: OC knowledge,
      which was low among young women in our study, was associated with OC continuation
      and common reasons for discontinuation. Continued efforts to characterize
      relationships between OC knowledge and behavior and to test the effectiveness of
      different components of interventions aimed at increasing knowledge, addressing
      side effects, and improving use of OCs are warranted.

PMID- 24571283
TI  - Agriculture, nutrition, and health in global development: typology and metrics
      for integrated interventions and research.
AB  - Despite rhetoric arguing that enhanced agriculture leads to improved nutrition
      and health, there is scant empirical evidence about potential synergies across
      sectors or about the mix of actions that best supports all three sectors. The
      geographic scale and socioeconomic nature of these interventions require
      integration of previously separate research methods. This paper proposes a
      typology of interventions and a metric of integration among them to help
      researchers build on each other's results, facilitating integration in methods to
      inform the design of multisector interventions. The typology recognizes the
      importance of regional effect modifiers that are not themselves subject to
      randomized assignment, and trade-offs in how policies and programs are
      implemented, evaluated, and scaled. Using this typology could facilitate
      methodological pluralism, helping researchers in one field use knowledge
      generated elsewhere, each using the most appropriate method for their situation. 

PMID- 24571285
TI  - Colorectal cancer among Indigenous and non-Indigenous people in Queensland,
      Australia: Toward survival equality.
AB  - AIM: While Indigenous people in Queensland have lower colorectal cancer (CRC)
      incidence and mortality than the rest of the population, CRC remains the third
      most frequent cancer among Australian Indigenous people overall. This study aimed
      to investigate patterns of care and survival between Indigenous and non
      Indigenous Australians with CRC. METHODS: Through a matched-cohort design we
      compared 80 Indigenous and 85 non-Indigenous people all diagnosed with CRC and
      treated in Queensland public hospitals during 1998-2004 (frequency matched on
      age, sex, geographical remoteness). We compared clinical and treatment data
      (Pearson's chi-square) and all-cause and cancer survival (Cox regression
      analysis). RESULTS: Indigenous patients with CRC were not significantly more
      likely to have comorbidity, advanced disease at diagnosis or less treatment than
      non-Indigenous people. There was also no statistically significant difference in
      all-cause survival (HR 1.14, 95% CI 0.69, 1.89) or cancer survival (HR 1.01, 95%
      CI 0.60, 1.69) between the two groups. CONCLUSIONS: Similar CRC mortality among
      Indigenous and other Australians may reflect both the lower incidence and
      adequate management. Increasing life expectancy and exposures to risk factors
      suggests that Indigenous people are vulnerable to a growing burden of CRC.
      Primary prevention and early detection will be of paramount importance to future
      CRC control among Indigenous Australians. Current CRC management must be
      maintained and include prevention measures to ensure that predicted increases in
      CRC burden are minimized.

PMID- 24571286
TI  - Renal cell carcinoma in adult patients with thalassaemia major: a description of
      three cases.

PMID- 24571287
TI  - Heteroleptic bis(cis-1,2-disubstituted ethylene-1,2-dithiolato)nickel complexes
      obtained by ligand-exchange reaction: synthesis and properties.
AB  - The ligand-exchange reaction has been investigated to synthesize nickel
      bis(dithiolene) complexes bearing one hydroxyl functional group aimed at being
      grafted thereafter onto polymer materials. This reaction leads easily to
      heteroleptic complexes with the ethylene-1,2-dithiolato core substituted by
      either alkyl or aryl moieties. Details on synthetic parameters are given. A
      direct link between the electronic properties of the obtained molecules and those
      of the parent complexes involved in the ligand-exchange reaction is highlighted
      and also demonstrates that this reaction is a powerful method for preparing
      nickel complexes with tailor-made frontier orbital energies. 

PMID- 24571288
TI  - CO2 enrichment alters diurnal stem radius fluctuations of 36-yr-old Larix decidua
      growing at the alpine tree line.
AB  - To understand how trees at high elevations might use water differently in the
      future, we investigated the effects of CO2 enrichment and soil warming
      (separately and combined) on the water relations of Larix decidua growing at the
      tree line in the Swiss Alps. We assessed diurnal stem radius fluctuations using
      point dendrometers and applied a hydraulic plant model using microclimate and
      soil water potential data as inputs. Trees exposed to CO2 enrichment for 9 yr
      showed smaller diurnal stem radius contractions (by 46 +/- 16%) and expansions
      (42 +/- 16%) compared with trees exposed to ambient CO2 . Additionally, there was
      a delay in the timing of daily maximum (40 +/- 12 min) and minimum (63 +/- 14
      min) radius values for trees growing under elevated CO2 . Parameters optimized
      with the hydraulic model suggested that CO2 -enriched trees had an increased flow
      resistance between the xylem and bark, representing a more buffered water supply
      system. Soil warming did not alter diurnal fluctuation dynamics or the CO2
      response. Elevated CO2 altered the hydraulic water flow and storage system within
      L. decidua trees, which might have contributed to enhanced growth during 9 yr of
      CO2 enrichment and could ultimately influence the future competitive ability of
      this key tree-line species.

PMID- 24571289
TI  - The evolution of the sexually selected sword in Xiphophorus does not compromise
      aerobic locomotor performance.
AB  - Sexual selection can increase morphological diversity within and among species.
      Little is known regarding how interspecific variation produced through sexual
      selection affects other functional systems. Here, we examine how morphological
      diversity resulting from sexual selection impacts aerobic locomotor performance.
      Using Xiphophorus (swordtail fish) and their close relatives (N = 19 species), we
      examined whether the evolution of a longer sexually selected sword affects
      critical swimming speed. We also examined the effect of other suborganismal,
      physiological, and morphological traits on critical swimming speed, as well as
      their relationship with sword length. In correlation analyses, we found no
      significant relationship between sword length and critical swimming speed.
      Unexpectedly, we found that critical swimming speed was higher in species with
      longer swords, after controlling for body size in multiple regression analyses.
      We also found several suborganismal and morphological predictors of critical
      swimming speed, as well as a significant negative relationship between sword
      length and heart and gill mass. Our results suggest that interspecific variation
      in sword length is not costly for this aspect of swimming performance, but
      further studies should examine potential costs for other types of locomotion and
      other components of Darwinian fitness (e.g., survivorship, life span). 

PMID- 24571290
TI  - Four screening instruments for frailty in older patients with and without cancer:
      a diagnostic study.
AB  - BACKGROUND: Frailty in older patients might influence treatment decisions.
      Frailty can be determined using a Comprehensive Geriatric Assessment (CGA), but
      this is time-consuming and expensive. Therefore we assessed the diagnostic value
      of four shorter screening instruments. METHODS: We tested the abbreviated CGA
      (aCGA), the Vulnerable Elders Survey-13 (VES-13), the Groningen Frailty Indicator
      (GFI) and the Geriatric 8 (G8). A full CGA including functional status, cognitive
      status, depression, nutrition and comorbidity was used as reference. A minimum of
      85% for both sensitivity and specificity was predefined as acceptable. Data were
      collected through personal interviews by trained interviewers. We assessed people
      aged >= 70 years: 108 patients with recently diagnosed cancer recruited in
      hospitals and 290 without cancer recruited by general practitioners in the
      Netherlands and Belgium.Frailty was defined as having impairment in at least two
      domains of the full CGA. We used original cut-offs for the screening instruments
      and calculated sensitivity, specificity, positive and negative diagnostic values
      and the percentage classified as frail. RESULTS: Sensitivity of aCGA was 79% and
      87% for patients with and without cancer; specificity was 59% and 64%.
      Sensitivity of VES-13 was 67% and 82% for patients with and without cancer;
      specificity was 70% and 79%. Sensitivity for GFI was 76% (in both groups) and
      specificity 73% (in both groups). Sensitivity for G8 was 87% and 75% for patients
      with and without cancer; specificity was 68% (in both groups). CONCLUSIONS: No
      screening instrument was acceptable according to our predefined minimum of 85%
      for both sensitivity and specificity. The diagnostic value of the investigated
      instruments is rather poor and one could wonder about their additional value to
      clinical judgment.

PMID- 24571292
TI  - Kinetics of CH4 and CO2 hydrate dissociation and gas bubble evolution via MD
      simulation.
AB  - Molecular dynamics simulations of gas hydrate dissociation comparing the behavior
      of CH4 and CO2 hydrates are presented. These simulations were based on a
      structurally correct theoretical gas hydrate crystal, coexisting with water. The
      MD system was first initialized and stabilized via a thorough energy
      minimization, constant volume-temperature ensemble and constant volume-energy
      ensemble simulations before proceeding to constant pressure-temperature
      simulations for targeted dissociation pressure and temperature responses. Gas
      bubble evolution mechanisms are demonstrated as well as key investigative
      properties such as system volume, density, energy, mean square displacements of
      the guest molecules, radial distribution functions, H2O order parameter, and
      statistics of hydrogen bonds. These simulations have established the essential
      similarities between CH4 and CO2 hydrate dissociation. The limiting behaviors at
      lower temperature (no dissociation) and higher temperature (complete melting and
      formation of a gas bubble) have been illustrated for both hydrates. Due to the
      shift in the known hydrate stability curves between guest molecules caused by the
      choice of water model as noted by other authors, the intermediate behavior (e.g.,
      260 K) showed distinct differences however. Also, because of the more hydrogen
      bonding capability of CO2 in water, as reflected in its molecular parameters,
      higher solubility of dissociated CO2 in water was observed with a consequence of
      a smaller size of gas bubble formation. Additionally, a novel method for
      analyzing hydrate dissociation based on H-bond breakage has been proposed and
      used to quantify the dissociation behaviors of both CH4 and CO2 hydrates.
      Activation energies Ea values from our MD studies were obtained and evaluated
      against several other published laboratory and MD values. Intrinsic rate
      constants were estimated and upscaled. A kinetic reaction model consistent with
      macroscale fitted kinetic models has been proposed to indicate the macroscopic
      consequences of this analysis. 

PMID- 24571291
TI  - Occurrence and distribution of Vibrio vulnificus and Vibrio parahaemolyticus-
      potential roles for fish, oyster, sediment and water.
AB  - Vibrio vulnificus and Vibrio parahaemolyticus are Gram-negative marine bacteria
      naturally found in estuaries such as the Gulf of Mexico and can be pathogenic to
      humans. We quantified both of these organisms in fish, oyster, sediment, and
      water using culture-independent (quantitative PCR; qPCR) and culture-dependent
      (direct plating-colony hybridization; DP-CH) techniques during the transition
      period between winter and spring. We correlated these levels to environmental
      conditions and to abundance of total bacteria and total vibrio. By qPCR, fish
      intestine samples had the highest V. vulnificus densities and were 2.7, 3.5, and
      4.2 logs greater than oyster, sediment and water samples, respectively. Densities
      of V. parahaemolyticus in fish samples by qPCR were 1.0, 2.1, and 3.1 logs
      greater than oyster, sediment and water samples, respectively. Similar
      differences between sample types were also observed by DP-CH. The difference
      between the more favourable and less favourable environmental conditions
      identified in this study was small (mean salinity 4.3 vs. 13 ppt). However, V.
      vulnificus and V. parahaemolyticus were consistently detected in fish intestines,
      but infrequently detected and at lower levels in oysters and during the less
      favourable period. This trend was observed by qPCR and DP-CH, indicating fish
      intestines are a significant source of pathogenic vibrios in the environment.
      SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first study to report the
      densities of Bacteria 16S rRNA, Vibrio 16S rRNA, Vibrio vulnificus, and V.
      parahaemolyticus in fish intestine, oyster, sediment and water samples, as well
      as compare these values through culture-dependent and culture-independent
      methodology. Vibrio vulnificus and V. parahaemolyticus were detected in samples
      of fish intestines by qPCR and colony hybridization when conditions were less
      favourable for their occurrence in the environment. In contrast, V. vulnificus
      and V. parahaemolyticus were infrequently detected and at lower levels in other
      niches examined. These results indicate that fish intestinal tracts are a
      significant source of these pathogens.

PMID- 24571293
TI  - Polymer/Perovskite-type nanoparticle multilayers with multielectric properties
      prepared from ligand addition-induced layer-by-layer assembly.
AB  - We introduce an adsorption mechanism for a layer-by-layer (LbL) assembly (i.e., a
      ligand addition-induced LbL assembly) and demonstrate that the
      (polymer/perovskite nanoparticle (NP))n nanocomposite films based on the ligand
      addition LbL exhibit ferroelectric and resistive switching properties. Oleic acid
      (OA)-stabilized BaTiO3 NPs (OA-BTO NPs) with a size of approximately 8 nm were
      LbL-assembled with amine-functionalized dendrimers (NH2-dendrimers) using the
      high affinity between NH2 moieties and Ti ions. The ferroelectric properties of
      the (NH2-dendrimer/OA-BTO NP)n multilayers were generated by the Ti disorder in
      the OA-BTO NP unit cell despite the use of sub-10 nm OA-BTO NPs (i.e., OA-BTO
      NPs), which are near the critical size for ferroelectric properties.
      Additionally, the (NH2-dendrimer/OA-BTO NP)n multilayers sandwiched between the
      bottom (platinum) and top (silver or tungsten) electrodes exhibited a resistive
      switching memory at a relatively low operating voltage below 2 V with a switching
      speed of approximately 100 ns and an ON/OFF current ratio of approximately 10(4).
      Furthermore, the ferroelectric and resistive switching properties could be
      further improved by controlling the bilayer number (n). We believe that our
      approach can provide a basis for designing and exploiting multifunctional memory
      electronics based on a variety of perovskite NPs with ferroelectric properties. 

PMID- 24571294
TI  - Influence of three anionic gemini surfactants with different chain lengths on the
      optical properties of a cationic polyfluorene.
AB  - The effects of three sulfonate gemini surfactants with different hydrophobic
      chain lengths (8, 10, and 12 carbon atoms) on the optical properties of a
      fluorene-based conjugated cationic polymer poly{[9,9-bis(6'-N,N,N
      trimethylammonium)hexyl]-fluorene-phenylene} bromide (PFP) dissolved in DMSO
      water solutions (4% v/v) or water were investigated, respectively. When
      surfactants with PFP dissolved in DMSO-water solutions (4% v/v) are incubated, a
      decrease in photoluminescence (PL) intensity and a red shift of emission maxima
      are obtained at low surfactant concentrations. Intriguingly, two different Stern
      Volmer constants (KSV1 and KSV2) are obtained and analyzed in detail for the
      first time. Further increase in the surfactant concentration enhanced PL
      intensity, and distinct blue shifts of both absorption and emission maxima are
      observed. Importantly, the turning point between the emission quenching and
      enhancement is closely related to the hydrophobic chain length: the longer the
      chain length, the earlier the turning point appears. Simulation studies provide
      strong evidence to explain these phenomena. Surface tension measurements show
      more insight on the interactions between PFP and surfactant. On the contrary, no
      emission quenching is obtained at low surfactant concentrations for PFP dissolved
      in water. 

PMID- 24571296
TI  - Broadening definitions of family for older lesbians: modifying the Lubben social
      network scale.
AB  - Lesbian seniors have triple vulnerability (gender, sexual orientation, and age),
      necessitating inquiry into their social support needs, yet research about that is
      scare. Investigators identify relationships between social support and senior
      health. The Lubben Social Network Scale, Revised (LSNS-R), has provided such
      evidence and has been used to study many diverse senior groups. We modified it to
      include a Family of Choice category and qualitative questions to give context to
      responses among a sample of older lesbians. Our pilot demonstrated that the
      modification made a difference in accurately measuring social support among the
      sample, yet further investigation is warranted. 

PMID- 24571295
TI  - The incidence of Freudian self-analysis in the construction of the psychoanalytic
      theory of anxiety.
AB  - The value and function of self-analysis has been a contentious issue in several
      studies dedicated to the Freudian legacy. For some writers, Freud's experience of
      self-analysis is rightly considered to be the master key to an understanding of
      the origins of the fundamentals of psychoanalysis. For others, the exaggerated
      importance attributed to the process merely led to the construction of a
      foundational myth. Nevertheless, if it is recognized to be a process in which
      Freud, in collaboration with Fliess, analysed personal aspects, working
      hypotheses and psychopathological debates, a reconsideration of self-analysis may
      contribute new elements to our understanding of the paths that were taken in the
      elaboration of the theory and practice of pyschoanalysis. Starting from this
      premise, the present work will consider the systematic examination that Freud
      conducted of his own phobia in the course of his self-analysis to be a process of
      great relevance to the elaboration of the early psychoanlytic conceptualizations
      of anxiety, in that in the course of this process the possible role of sexuality,
      fantasy, memory and unconscious determinism in the etiology of anxiety became
      part of the discussion. 

PMID- 24571298
TI  - Cutaneous adverse food reactions in cats: retrospective evaluation of 17 cases in
      a dermatology referral population (2001-2011).
AB  - OBJECTIVE: To better characterise cutaneous adverse food reactions (AFR) in cats,
      including the diagnostic challenges. DESIGN: Retrospective evaluation of cases
      presenting to a dermatology referral service. METHODS: Cats were identified by a
      computerised medical record search. AFR was confirmed by clear deterioration on
      normal food re-challenge after completing an elimination diet, followed by
      improvement returning to the test diet. Prevalence, and breed, sex or age
      predispositions were compared with the base referral population. Patient records
      were reviewed for historical features, clinical presentations, concurrent
      dermatoses and dietary details. RESULTS: A total of 17 cats were identified with
      cutaneous AFR, with no breed or sex predisposition determined. Age of onset
      ranged from 3 months to 9 years, with a mean of 3.5 years. Prevalence was 6% of
      dermatoses and 10% of cutaneous hypersensitivities in the referral cat
      population. Cats typically presented with severe, perennial, non-seasonally
      flaring pruritus affecting the face/head, neck and/or ventral abdomen. Concurrent
      hypersensitivities were confirmed in 6 cats and/or suspected in another 5 cats.
      Home-prepared elimination diets were completed by 16 cats; 8 cats had initial
      poor response to minimum 6-week commercial hydrolysed protein diets. Identified
      adverse foods included fish in 2 cats, and chicken, beef, commercial dry, and
      some canned foods, each in 1 cat. CONCLUSIONS: The prevalence of cutaneous AFR in
      the general cat population is likely to be greater than 6%. A range of clinical
      presentations occur and practical challenges to diagnosis include reliance on
      strict adherence to dietary exclusion/provocation trials and misleading responses
      related to concurrent dermatoses and owner perceptions.

PMID- 24571299
TI  - Haematological and biochemical variations among eight sighthound breeds.
AB  - OBJECTIVE: The aim of the study was to compare the haematological and biochemical
      profiles of eight sighthound breeds. DESIGN: Samples were taken from 192
      individuals of the sighthound breeds (Whippet, Greyhound, Italian Greyhound,
      Sloughi, Saluki, Borzoi, Pharaoh Hound and Azawakh). Routine haematological and
      biochemical examinations were performed and the results were evaluated
      statistically. RESULTS: There were significant differences in haematology and
      clinical biochemistry among the sighthound breeds. The most similar laboratory
      profile to Greyhounds was found in Whippets. Italian Greyhounds had significantly
      higher alanine aminotransferase activity than other sighthounds, except Pharaoh
      Hounds. CONCLUSION: Application of the Greyhound laboratory profile to other
      sighthounds is not recommended because of the frequent differences in
      haematological and clinical biochemical reference intervals.

PMID- 24571300
TI  - Unique presentation of normolipaemic cutaneous xanthoma in a cat.
AB  - CASE REPORT: A normolipaemic 7-year-old female spayed Domestic Shorthair was
      initially presented with a history of pruritus for several years and diagnosed
      with concurrent atopic dermatitis, flea bite hypersensitivity and adverse food
      reaction. The hypersensitivities were controlled with cyclosporin, allergen
      specific immunotherapy, topical flea control and a restricted diet. Five months
      after initial presentation, the cat developed a non-healing nodular ulcerated
      cutaneous lesion in the left axilla and also developed immune-mediated haemolytic
      anaemic (IMHA). The IMHA was stabilised, but the axillary lesion persisted and
      progressed to a diffuse, firm, yellowed subcutaneous swelling over the ventral
      body approximately 20 months later. Histopathology was consistent with cutaneous
      xanthoma. The cat was normolipaemic and being fed a home-prepared diet of lean
      kangaroo meat and pumpkin to manage pruritus associated with adverse food
      reactions. No underlying malignancy was detected on routine screening tests.
      CONCLUSION: A diffuse, planar form of cutaneous xanthoma occurring without
      associated lipaemia has not been previously reported in cats.

PMID- 24571301
TI  - Incidence of calf scours and associated risk factors in southern New South Wales
      beef herds.
AB  - OBJECTIVE: The aim of this study was to identify the incidence of morbidity and
      mortality associated with calf scours in beef calves between birth and 14 days of
      age. Farm characteristics, animal factors and management practices were also
      assessed for any association with calf scours being present on the farm. METHODS:
      A questionnaire and return address envelope were distributed to 721 farms with at
      least 50 head of beef cattle in the Hume area of New South Wales, Australia.
      RESULTS: In total, 147 (20.4%) farmers responded to the survey, of which 76
      (51.7%) indicated calf scours did occur on their farm. On average, farmers
      estimated the morbidity of calf scours was 4.5%, but only 0.2% of all calves died
      as a result of scours. Affected herds were more likely to have multiple breeds
      and a higher proportion of cows with mismothering problems or weak calves
      compared with unaffected herds. These differences were confirmed with regression
      analysis. A large proportion of farmers with affected herds reported the loss of
      many calves from 'unexplained' or 'sudden' death within the first 14 days of
      life. CONCLUSIONS: The incidence of calf morbidity was lower and mortality was
      within the same range compared with other studies on beef farms around the world.
      The high percentage of farms reporting losses from 'unexplained' or 'sudden'
      death of calves requires further monitoring and diagnostic and economic
      investigations.

PMID- 24571302
TI  - Ureaplasma diversum in bull semen in Australia: its detection and potential
      effects.
AB  - BACKGROUND: The primary objective of this study was to confirm the infection
      status of Ureaplasma diversum in Australian bulls and to identify morphological
      changes of sperm from U. diversum-positive bulls. METHODS: Fresh semen samples
      were taken from 29 sexually active beef bulls from suspect herds in the
      Riverina/Upper Murray region. U. diversum was identified using PCR analyses and
      culture of the organism. RESULTS: Nine of the bulls were PCR-positive for U.
      diversum but none of these had genital lesions. Sperm from infected bulls showed
      increased incidence of abnormal tails (bent and coiled), as well as surface
      abnormalities (i.e. small protuberances or lumps). CONCLUSIONS: The results
      suggest impairment of sperm function and possibly fertility. Further
      investigations into the potential role of U. diversum as a pathogen for
      Australian cattle are warranted.

PMID- 24571303
TI  - Suspected Lythrum hyssopifolia (lesser loosestrife) poisoning of cattle.
AB  - CASE REPORT: Morbidity and mortality in two herds of cattle in southern New South
      Wales were associated with ingestion of lesser or hyssop loosestrife (Lythrum
      hyssopifolia). Clinical signs in adult cows included depression, listlessness,
      inappetence, anorexia and recumbency. Deaths occurred in 16/48 (33.3%) and 4/60
      (6.7%) adult cows, but calves in both herds were unaffected. Elevated
      concentrations of urea and creatinine were present in the serum of one clinically
      affected cow and an elevated concentration of urea was detected in the aqueous
      humour of one cow that died. On histopathological examination, there was severe,
      acute necrosis of the proximal convoluted tubular epithelial cells in the kidneys
      of both affected cattle examined. CONCLUSION: There is strong evidence that
      lesser loosestrife is nephrotoxic for cattle.

PMID- 24571304
TI  - Neuroangiostrongyliasis due to Angiostrongylus cantonensis in gang-gang cockatoos
      (Callocephalon fimbriatum).
AB  - CASE REPORT: Four gang-gang cockatoos from an aviary in Sydney displayed severe
      neurological signs. Three were necropsied and histopathology of the brains and
      spinal cords revealed migrating nematodes, which were identified as
      Angiostrongylus cantonensis. The migrating larval nematodes created tracts of
      malacia in the brain, but elicited little inflammatory cell infiltration.
      However, adult nematodes that had emerged onto the meningeal surface of the
      spinal cord evoked a marked non-suppurative reaction. Detailed histological
      examination of other tissues revealed larvae embedded in arterioles in the
      gastrointestinal serosa, lung and heart, which were associated with a significant
      granulomatous response. The latter lesions were consistent with our understanding
      of the pathogenesis of infection with this parasite, but have not been previously
      described, probably as a result of limited sampling. CONCLUSIONS: Angiostrongylus
      cantonensis is still present in the Sydney area and can cause significant disease
      in exposed animals, including birds. It also highlights potential human health
      problems.

PMID- 24571305
TI  - Population dynamics of feral horses (Equus caballus) following above-average
      rainfall in a semi-arid environment of Australia.
AB  - BACKGROUND: Recent record rainfall in much of semi-arid Central Australia is the
      most likely reason for a feral horse population increase in excess of normal.
      Uncontrolled numbers of feral horses have habitat degradation and animal welfare
      implications. OBJECTIVES: The aims of this study were to investigate the social
      structure of feral horses and assess their population growth rate following
      unseasonably high rainfall. METHODS: The study area was 4000 km(2) of unmanaged,
      semi-arid country in Central Australia (latitude 24.50 degrees S, longitude
      132.10 degrees E). Horses were identified by descriptive features from ground
      searches, movement-activated cameras and 'hides' positioned at key water holes.
      Wherever possible, sex and age categories were documented. Population growth rate
      was estimated by the number of foals divided by the number of horses older than 1
      year in the observed population. RESULTS: A total of 1424 horses were identified
      and categorised, of which 335 were foals born within the current year. Only 123
      juveniles were identified. Of the adult horses, 53.4% were male and 46.6% were
      female and this differed from parity (P = 0.04). Of the mares, 71.9% had a foal
      at foot and the population growth rate was 29.5%. CONCLUSIONS: With a sustained
      population growth rate of 29.5%, this population of feral horses will more than
      double within 3 years. The high population increase will likely have a
      detrimental effect on native fauna and flora and the fragile, semi-arid
      ecosystems of Central Australia. After a period of high rainfall and plentiful
      resources, 'normal' drought conditions will return and many feral horses will
      starve and die as they compete for limited resources.

PMID- 24571306
TI  - Pet ownership in Australia.

PMID- 24571308
TI  - Cross-linked supramolecular polymer gels constructed from discrete multi
      pillar[5]arene metallacycles and their multiple stimuli-responsive behavior.
AB  - A new family of discrete hexakis-pillar[5]arene metallacycles with different
      sizes have been successfully prepared via coordination-driven self-assembly,
      which presented very few successful examples of preparation of discrete multiple
      pillar[n]arene derivatives. These newly designed hexakis-pillar[5]arene
      metallacycles were well characterized with one-dimensional (1-D) multinuclear NMR
      ((1)H and (31) P NMR), two-dimensional (2-D) (1)H-(1)H COSY and NOESY, ESI-TOF
      MS, elemental analysis, and PM6 semiempirical molecular orbital methods.
      Furthermore, the host-guest complexation of such hexakis-pillar[5]arene hosts
      with a series of different neutral ditopic guests G1-6 were well investigated.
      Through host-guest interactions of hexakis-pillar[5]arene metallacycles H2 or H3
      with the neutral dinitrile guest G5, the cross-linked supramolecular polymers
      H2?(G5)3 or H3?(G5)3 were successfully constructed at the high-concentration
      region, respectively. Interestingly, these cross-linked supramolecular polymers
      transformed into the stable supramolecular gels upon increasing the
      concentrations to a relatively high level. More importantly, by taking advantage
      of the dynamic nature of metal-ligand bonds and host-guest interactions, the
      reversible multiple stimuli-responsive gel-sol phase transitions of such polymer
      gels were successfully realized under different stimuli, such as temperature,
      halide, and competitive guest, etc. The mechanism of such multiple stimuli
      responsive processes was well illustrated by in situ multinuclear NMR
      investigation. This research not only provides a highly efficient approach to the
      preparation of discrete multiple pillar[n]arene derivatives but also presents a
      new family of multiple stimuli-responsive "smart" soft matters. 

PMID- 24571307
TI  - Parallel tagged amplicon sequencing of transcriptome-based genetic markers for
      Triturus newts with the Ion Torrent next-generation sequencing platform.
AB  - Next-generation sequencing is a fast and cost-effective way to obtain sequence
      data for nonmodel organisms for many markers and for many individuals. We
      describe a protocol through which we obtain orthologous markers for the crested
      newts (Amphibia: Salamandridae: Triturus), suitable for analysis of interspecific
      hybridization. We use transcriptome data of a single Triturus species and design
      96 primer pairs that amplify c. 180 bp fragments positioned in 3-prime
      untranslated regions. Next, these markers are tested with uniplex PCR for a set
      of species spanning the taxonomical width of the genus Triturus. The 52 markers
      that consistently show a single band of expected length at gel electrophoreses
      for all tested crested newt species are then amplified in five multiplex PCRs
      (with a plexity of ten or eleven) for 132 individual newts: a set of 84
      representing the seven (candidate) species and a set of 48 from a presumed hybrid
      population. After pooling multiplexes per individual, unique tags are ligated to
      link amplicons to individuals. Subsequently, individuals are pooled equimolar and
      sequenced on the Ion Torrent next-generation sequencing platform. A
      bioinformatics pipeline identifies the alleles and recodes these to a genotypic
      format. Next, we test the utility of our markers. baps allocates the 84 crested
      newt individuals representing (candidate) species to their expected (candidate)
      species, confirming the markers are suitable for species delineation. newhybrids,
      a hybrid index and hiest confirm the 48 individuals from the presumed hybrid
      population to be genetically admixed, illustrating the potential of the markers
      to identify interspecific hybridization. We expect the set of markers we designed
      to provide a high resolving power for analysis of hybridization in Triturus. 

PMID- 24571309
TI  - Synthesis of sterically hindered N-acylated amino acids from N-carboxyanhydrides.
AB  - Sterically hindered N-acyl, gem-disubstituted amino acids are easily prepared via
      the addition of organometallic reagents to N-carboxyanhydrides (NCA). The process
      tolerates a wide variety of functional groups and allows the synthesis of amide
      products not readily accessible by traditional acylation chemistry. The existence
      of an isocyanate intermediate was established by in situ IR spectroscopy. 

PMID- 24571311
TI  - HPLC-based activity profiling for GABAA receptor modulators in Adenocarpus
      cincinnatus.
AB  - In a two-microelectrode voltage clamp assay with Xenopus laevis oocytes, a
      dichloromethane extract of Adenocarpus cincinnatus roots and tubers (Leguminosae)
      enhanced the GABA-induced chloride current (IGABA) through receptors of the
      subtype alpha1beta2gamma2s by 126.5 +/- 25.1% when tested at 100 MUg/mL. By means
      of HPLC-based activity profiling, 15 flavonoid and isoflavonoid derivatives,
      including eight new compounds, were identified in the active fractions of the
      extract. Isoflavone 11 and pterocarpans 2 and 8 showed promising activity in the
      oocyte assay, with EC50 values between 2.8 +/- 1.4 and 18.8 +/- 2.3 MUM. Maximal
      potentiation of IGABA ranged between 490% and 640%. This is the first report of
      pterocarpans as GABAA receptor modulators. 

PMID- 24571312
TI  - Intraoperative goal-directed fluid therapy--which goals should we choose?

PMID- 24571310
TI  - BMI1 reprogrammes histone acetylation and enhances c-fos pathway via directly
      binding to Zmym3 in malignant myeloid progression.
AB  - The polycomb group BMI1 is proved to be crucial in malignant myeloid progression.
      However, the underlying mechanism of the action of BMI1 in myeloid malignant
      progression was not well characterized. In this study, we found that the patients
      of both myelodysplastic syndromes and chronic myeloid leukaemia with BMI1
      overexpression had a higher risk in malignant myeloid progression. In vitro gene
      transfection studies showed that BMI1 inhibited cell myeloid and erythroid
      differentiation induced by 12-O-tetradecanoyl phorbol-13-acetate (TPA) and
      histone deacetylase inhibitor sodium butyrate respectively. BMI1 also resisted
      apoptosis induced by arsenic trioxide. Moreover, the transcript levels of Runx1
      and Pten were down-regulated in Bmi1-transfected cells in company with histone
      deacetylation modification. By using chromatin immunoprecipitation (ChIP)
      collaborated with secondary generation sequencing and verified by ChIP-PCR, we
      found that BMI1 directly bound to the promoter region of Zmym3, which encodes a
      component of histone deacetylase-containing complexes. In addition, as one of the
      downstream target genes of this complex, c-fos was activated with increasing
      histone acetylation when ZMYM3 was suppressed in the Bmi1-transfected cells.
      These results suggested that BMI1 may reprogramme the histone acetylation profile
      in multiple genes through either indirect or direct binding effects which
      probably contributes to the malignant progression of myeloid progenitor cells. 

PMID- 24571313
TI  - A pooled analysis of individual patient data from registrational trials of
      silodosin in the treatment of non-neurogenic male lower urinary tract symptoms
      (LUTS) suggestive of benign prostatic hyperplasia (BPH).
AB  - OBJECTIVE: To evaluate the efficacy and safety of silodosin in a pooled analysis
      based on individual patients data from three randomised controlled trials (RCTs)
      comparing silodosin and placebo. PATIENTS AND METHODS: A pooled analysis of 1494
      patients from three 12-week, similarly designed, parallel-group, multicentre,
      randomised, double-blind, placebo-controlled phase III RCTs (SI04009, SI04010,
      KMD3213-IT-CL 0215) was performed. Differences from placebo for the mean change
      from baseline to the end of treatment for the International Prostate Symptom
      Score (IPSS) and uroflowmetry data were tested using an analysis of covariance
      model. RESULTS: At study end, in the intention-to-treat population, silodosin was
      significantly more effective than placebo in improving IPSS total score (adjusted
      means differences [AMD] 2.7; P < 0.001). Silodosin was significantly more
      effective than placebo in improving storage, voiding, and quality-of-life-item
      subscores (all P < 0.001). Similarly, silodosin was more effective than placebo
      in improving maximum urinary flow rate (Qmax ; AMD 0.8; P = 0.002). The most
      frequently reported adverse event (AE) was ejaculatory dysfunction, reported in
      186 (22%) patients in the silodosin group and six (0.9%) in the placebo group
      (odds ratio 28.14; P < 0.001). Dizziness and orthostatic hypotension rates were
      similar in silodosin and placebo groups. CONCLUSIONS: Silodosin is an effective
      treatment for male lower urinary tract symptoms suggestive of benign prostatic
      hyperplasia. The drug is able to improve total IPSS, all IPSS-related parameters,
      and Qmax at uroflowmetry. Ejaculatory dysfunction is the main treatment-related
      AE, whereas prevalence of cardiovascular AEs was similar to placebo.

PMID- 24571321
TI  - Bladder function of patients with Parkinson's disease.
AB  - Bladder function of patients with Parkinson's disease alters significantly: the
      majority of patients have overactive bladder (urinary urgency/frequency) with
      little or no post-void residuals. This seems to be the result of an altered brain
      bladder relationship, as in Parkinson's disease, the frontal-basal ganglia D1
      dopaminergic circuit that normally suppresses the micturition reflex is altered.
      The pathophysiology of the bladder dysfunction in Parkinson's disease differs
      from that in multiple system atrophy; therefore, it might also aid in
      differential diagnosis. The effects of levodopa, the major drug to treat motor
      dysfunction, on the bladder in Parkinson's disease vary significantly; therefore,
      add-on therapy is often required. Anticholinergic drugs are the first-line
      treatment, with particular care for cognitive function in elderly patients. The
      second-line treatment includes serotonergics drug, desmopressin and others. Newer
      modalities include deep brain stimulation that improves the bladder in
      Parkinson's disease; and botulinum toxin is promising, particularly in difficult
      cases. These treatments might be beneficial in maximizing the patients' quality
      of life. 

PMID- 24571322
TI  - Simulator practice is not enough to become a robotic surgeon: the driving lessons
      model.

PMID- 24571323
TI  - Older driver estimates of driving exposure compared to in-vehicle data in the
      Candrive II study.
AB  - OBJECTIVE: Most studies on older adults' driving practices have relied on self
      reported information. With technological advances it is now possible to
      objectively measure the everyday driving of older adults in their own vehicles
      over time. The purpose of this study was to examine the ability of older drivers
      to accurately estimate their kilometers driven over one year relative to
      objectively measured driving exposure. METHODS: A subsample (n = 159 of 928;
      50.9% male) of Candrive II participants (age >= 70 years of age) was used in
      these analyses based on strict criteria for data collected from questionnaires as
      well as an OttoView-CD Autonomous Data Logging Device installed in their vehicle,
      over the first year of the prospective cohort study. RESULTS: Although there was
      no significant difference overall between the self-reported and objectively
      measured distance categories, only moderate agreement was found (weighted kappa =
      0.57; 95% confidence interval, 0.47-0.67). Almost half (45.3%) chose the wrong
      distance category, and some people misestimated their distance driven by up to
      20,000 km. Those who misjudged in the low mileage group (<=5000 km) consistently
      underestimated, whereas the reverse was found for those in the high distance
      categories (>= 20,000); that is, they always overestimated their driving
      distance. CONCLUSIONS: Although self-reported driving distance categories may be
      adequate for studies entailing broad group comparisons, caution should be used in
      interpreting results. Use of self-reported estimates for individual assessments
      should be discouraged.

PMID- 24571324
TI  - An analysis of sexual size dimorphism in goose.
AB  - 1. Sexual size dimorphism (SSD) is a common phenomenon in animals. Rensch's rule
      states that larger species generally exhibit a higher male to female body size
      ratio than smaller ones. 2. Domesticated animals offer excellent opportunities
      for testing predictions of the functional explanations of Rensch's rule and this
      was tested in a meta-analysis of SSD in 38 breeds of domestic geese compared
      among themselves and with their wild relatives (subfamily Anserinae, 35 species).
      3. Domestic geese and wild Anser species taken together supported Rench's rule
      but the wild species did not. 4. The non-targeted sex selection hypothesis seems
      to provide the best intuitive explanation for the lack of SSD in geese.

PMID- 24571328
TI  - Matrix supported poly(2-oxazoline)-based hydrogels for DNA catch and release.
AB  - We describe the synthesis of matrix supported hydrogel structures based on amine
      containing poly(2-oxazoline)s and their use to bind and release genetic material
      for potential applications in diagnostics or pathogen detection. Amine containing
      poly(2-oxazoline)s were synthesized by copolymerization of 2-ethyl-2-oxazoline
      with a monomer bearing a tert-butyl oxycarbonyl (Boc) protected amine group in
      the 2-position and subsequent deprotection. The statistical copolymers were used
      to generate hydrogels and matrix supported hydrogels by cross-linking of a
      certain fraction of the amine groups with epichlorhydrin. Supported structures
      were prepared by soaking porous polyethylene (PE) or polypropylene (PP) filter
      materials in a copolymer/epichlorhydrin solution, which was cross-linked upon
      heating. Scanning electron microscopy (SEM) of the composites revealed a bead
      like structure of the gel phase, which could be attributed to a lower critical
      solution temperature (LCST) behavior of the initial polymer prior to gelation.
      The dependency of the LCST behavior on the content of amine groups was
      investigated. Swelling values and the ratio of hydrogel per composite was
      determined using water sorption analysis. Subsequently, the ability of the
      systems to absorb and release labeled DNA was tested. Uptake and stimulated
      release, triggered by changes in pH, temperature, and heparin concentration, were
      investigated using fluorescence microscopy. Polymerase chain reaction (PCR)
      proved the successful recovery of the DNA, demonstrating the potential of the
      presented system for a broad range of molecular biological applications. 

PMID- 24571327
TI  - Strigolactone analog GR24 triggers changes in PIN2 polarity, vesicle trafficking
      and actin filament architecture.
AB  - Strigolactones (SLs) are plant hormones that regulate shoot and root development
      in a MAX2-dependent manner. The mechanism underlying SLs' effects on roots is
      unclear. We used root hair elongation to measure root response to SLs. We
      examined the effects of GR24 (a synthetic, biologically active SL analog) on
      localization of the auxin efflux transporter PIN2, endosomal trafficking, and F
      actin architecture and dynamics in the plasma membrane (PM) of epidermal cells of
      the primary root elongation zone in wildtype (WT) Arabidopsis and the SL
      insensitive mutant max2. We also recorded the response to GR24 of trafficking
      (tir3), actin (der1) and PIN2 (eir1) mutants. GR24 increased polar localization
      of PIN2 in the PM of epidermal cells and accumulation of PIN2-containing
      brefeldin A (BFA) bodies, increased ARA7-labeled endosomal trafficking, reduced F
      actin bundling and enhanced actin dynamics, all in a MAX2-dependent manner. Most
      of the der1 and tir3 mutant lines also displayed reduced sensitivity to GR24 with
      respect to root hair elongation. We suggest that SLs increase PIN2 polar
      localization, PIN2 endocytosis, endosomal trafficking, actin debundling and actin
      dynamics in a MAX2-dependent fashion. This enhancement might underlie the WT
      root's response to SLs, and suggests noncell autonomous activity of SLs in roots.

PMID- 24571325
TI  - Application of toxicogenomic profiling to evaluate effects of benzene and
      formaldehyde: from yeast to human.
AB  - Genetic variation underlies a significant proportion of the individual variation
      in human susceptibility to toxicants. The primary current approaches to identify
      gene-environment (GxE) associations, genome-wide association studies and
      candidate gene association studies, require large exposed and control populations
      and an understanding of toxicity genes and pathways, respectively. This limits
      their application in the study of GxE associations for the leukemogens benzene
      and formaldehyde, whose toxicity has long been a focus of our research. As an
      alternative approach, our published work has applied innovative in vitro
      functional genomics testing systems, including unbiased functional screening
      assays in yeast and a near-haploid human bone marrow cell line. Through
      comparative genomic and computational analyses of the resulting data, human genes
      and pathways that may modulate susceptibility to benzene and formaldehyde were
      identified, and the roles of several genes in mammalian cell models were
      validated. In populations occupationally exposed to low levels of benzene, we
      applied peripheral blood mononuclear cell transcriptomics and chromosome-wide
      aneuploidy studies in lymphocytes. In this review, we describe our comprehensive
      toxicogenomic approach and the potential mechanisms of toxicity and
      susceptibility genes identified for benzene and formaldehyde, as well as related
      studies conducted by other researchers. 

PMID- 24571330
TI  - Central nervous system multiple myeloma: a different cytogenetic profile.

PMID- 24571329
TI  - Performance of commercial dengue NS1 ELISA and molecular analysis of NS1 gene of
      dengue viruses obtained during surveillance in Indonesia.
AB  - BACKGROUND: Early diagnosis of dengue infection is crucial for better management
      of the disease. Diagnostic tests based on the detection of dengue virus (DENV)
      Non Structural Protein 1 (NS1) antigen are commercially available with different
      sensitivities and specificities observed in various settings. Dengue is endemic
      in Indonesia and clinicians are increasingly using the NS1 detection for dengue
      confirmation. This study described the performance of Panbio Dengue Early NS1 and
      IgM Capture ELISA assays for dengue detection during our surveillance in eight
      cities in Indonesia as well as the genetic diversity of DENV NS1 genes and its
      relationship with the NS1 detection. METHODS: The NS1 and IgM/IgG ELISA assays
      were used for screening and confirmation of dengue infection during surveillance
      in 2010-2012. Collected serum samples (n = 440) were subjected to RT-PCR and
      virus isolation, in which 188 samples were confirmed for dengue infection. The
      positivity of the ELISA assays were correlated with the RT-PCR results to obtain
      the sensitivity of the assays. The NS1 genes of 48 Indonesian virus isolates were
      sequenced and their genetic characteristics were studied. RESULTS: Using
      molecular data as gold standard, the sensitivity of NS1 ELISA assay for samples
      from Indonesia was 56.4% while IgM ELISA was 73.7%. When both NS1 and IgM results
      were combined, the sensitivity increased to 89.4%. The NS1 sensitivity varied
      when correlated with city/geographical origins and DENV serotype, in which the
      lowest sensitivity was observed for DENV-4 (19.0%). NS1 sensitivity was higher in
      primary (67.6%) compared to secondary infection (48.2%). The specificity of NS1
      assay for non-dengue samples were 100%. The NS1 gene sequence analysis of 48
      isolates revealed the presence of polymorphisms of the NS1 genes which apparently
      did not influence the NS1 sensitivity. CONCLUSIONS: We observed a relatively low
      sensitivity of NS1 ELISA for dengue detection on RT-PCR-positive dengue samples.
      The detection rate increased significantly when NS1 data was combined with IgM.
      In our study, the low sensitivity of NS1 antigen detection did not relate to NS1
      genetic diversity. Rather, the performance of the NS1 antigen test was affected
      by the infection status of patients and geographical origin of samples.

PMID- 24571331
TI  - Nimotuzumab, a humanized monoclonal antibody specific for the EGFR, in
      combination with temozolomide and radiation therapy for newly diagnosed
      glioblastoma multiforme: First results in Chinese patients.
AB  - AIM: To evaluate the safety and efficacy of nimotuzumab, a humanized monoclonal
      antibody specific for the epidermal growth factor receptor (EGFR), in combination
      with temozolomide (TMZ) and radiation therapy (RT) in the treatment of newly
      diagnosed glioblastoma (GBM) in Chinese patients. METHODS: Twenty-six patients
      with newly diagnosed GBM were enrolled. All patients received standard external
      beam RT after surgery, with a total dose of 60 Gy in 30 fractions. During RT,
      concurrent TMZ was given daily at 75 mg/m(2) for 40-42 days, combined with six
      weekly infusions of nimotuzumab at a 200 mg dose. After a 4-week interval upon
      completion of RT, six cycles of adjuvant TMZ (150 to 200 mg/m(2) for 5 days in
      each 28-day cycle) were given. The primary end point was 6-month progression-free
      survival (PFS) rate. EGFR expression in tumor tissues was analyzed by
      immunohistochemistry. RESULTS: Treatment was well tolerated and no grade III or
      higher grade toxicity was observed. Median PFS and overall survival (OS) were
      10.0 and 15.9 months, respectively, while the 6-month PFS and OS rates were 69.2%
      and 88.5%, respectively. No correlation between efficacy and EGFR expression was
      found. CONCLUSIONS: Combination of Nimotuzumab with RT plus concomitant and
      adjuvant TMZ showed favorable safety and tolerability profiles in newly diagnosed
      GBM in Chinese patients. The survival times were similar to those seen in
      historical data of standard therapy.

PMID- 24571332
TI  - Dental attendance among older adults with intellectual disabilities in Ireland.
AB  - PURPOSE: To investigate dental attendance patterns and reasons for nonattendance
      among older adults with intellectual disabilities (ID) in Ireland. METHODS: A
      cross-sectional survey of quantitative data and text analysis of qualitative data
      drawn from a nationally representative sample of 753 people with ID over 40 years
      of age in Ireland. Participants were considered as regular or irregular dental
      attenders for analysis of quantitative data. Text analysis grouped open-ended
      responses for analysis. RESULT: There were slightly more females. Mean age was
      54.1 years (SD = 8.8). Almost half had moderate ID. A majority (86.5%) of
      respondents attended dental services within the last 2 years. Age and type of
      residence were associated with frequency of attendance (p < .01), as were dentate
      status and reported oral problems (p < .001). Text analysis revealed a lack of
      perceived need as a reason for not attending regularly. CONCLUSION: Older people
      with ID in Ireland report a very high level of regular dental attendance.
      Irregular attenders did not attend because they saw no need. There is a need to
      further study the importance of regular dental attendance for this population.

PMID- 24571333
TI  - "Water flowing uphill is one of the commonest facts of nature": the emergence of
      a visual language for groundwater geology.

PMID- 24571334
TI  - Vicinal difunctionalization of alkenes: chlorotrifluoromethylation with CF3SO2Cl
      by photoredox catalysis.
AB  - Photoredox-catalyzed vicinal chlorotrifluoromethylation of alkene is described.
      In the presence of Ru(Phen)3Cl2, CF3SO2Cl was used as a source for the CF3
      radical and chloride ion under visible light irradiation. Various terminal and
      internal alkenes were transformed to their vicinal chlorotrifluoromethylated
      derivatives. Biologically active compounds were applied under the condition to
      obtain desired products, suggesting that the method could be feasible for late
      stage modification in drug discovery. 

PMID- 24571335
TI  - In this issue-March 2014: Emergency disease preparedness in the pig industry .
      Reducing mortalities in Merino ewes . Persicaria toxicity in beef cows . Vaginal
      smears in ovulating cats . Small gauge needles suitable for venepuncture .
      Osteotomy and locking plates for fracture malunion . Neoureterostomy with distal
      ureter in situ . Diagnostic challenge.

PMID- 24571336
TI  - Emergency disease planning and preparedness.

PMID- 24571337
TI  - Poor quality photomicrographs.

PMID- 24571338
TI  - Risk factors for Merino ewe mortality on the Northern Tablelands of New South
      Wales, Australia.
AB  - OBJECTIVE: To measure the association of worm egg count (WEC), body weight (BW)
      and fat score (FS) with mortality in Merino ewes. METHODS: On six farms, Merino
      ewes (n = 1440) were yarded at approximately 3-month intervals for 2 years for a
      range of experimental measurements. Mortality was defined by failure to present
      at two consecutive measurement days and at next shearing. Survival analysis was
      conducted with phenotypic traits measured both as continuous variables and
      categorised appropriately for industry guidelines. RESULTS: Overall mortality was
      10%, with most deaths occurring in autumn followed by winter. Age class (2006
      drop vs mature-age ewes) did not affect mortality. High WEC, low BW and low FS
      significantly increased the risk of mortality. WEC > 1200 epg significantly
      increased risk of mortality in summer (risk ratio 3.76) and autumn (risk ratio
      3.61) compared with the reference group. Risk of mortality increased 1.1-fold for
      each kilogram unit decrease in BW and 7-fold for each unit decrease in FS.
      CONCLUSIONS: Mortality of Merino ewes can be significantly reduced by management
      methods that reduce WEC, maintain BW and increase the FS. For Merino ewes on the
      Northern Tablelands of NSW, improved animal welfare and economic benefits may be
      achieved by maintaining sheep with WEC < 1200 epg, BW > 35 kg and FS > 2.5.

PMID- 24571339
TI  - Liver necrosis and photosensitisation in cattle after eating Persicaria
      lapathifolia (pale knotweed) and Persicaria orientalis (Prince's feather).
AB  - Cattle deaths in two contemporaneous incidents were attributed to acute
      intoxication with Persicaria lapathifolia and P. orientalis when the plants were
      under heat and moisture stress. To our knowledge this is the first confirmed
      report of acute, fatal hepatic necrosis associated with ingestion of these
      plants. 

PMID- 24571340
TI  - Vaginal cytology after induction of ovulation in the queen: comparison of
      postoestrus and dioestrus.
AB  - OBJECTIVE: To compare the vaginal cytology of ovulating and non-ovulating queens.
      PROCEDURE: The study group comprised 15 queens showing behavioural oestrus.
      Ovulation was induced in 7 (dioestrus group) and 8 were left untreated
      (postoestrus group). Vaginal smears were collected from all animals prior to
      ovariohysterectomy on day 7. Epithelial cells were classified as basal-parabasal,
      intermediate, superficial, or anucleated superficial cells and counted using
      computer-assisted image analysis. From each smear, 50 representative vaginal
      epithelial cells were chosen. Digital images of cells were taken and cell area,
      cytoplasm area, nucleus area, cell diameter, cell perimeter, nucleus/cytoplasm
      ratio and red-green-blue (RGB) values were measured using image analysis
      software. Measurement data were compared between groups. RESULTS: Ovulation
      induction was successful in all animals. The swabbing procedure in oestrus did
      not induce ovulation in any postoestrus queens. Mean duration of oestrus was 6.65
      +/- 0.44 and 4.71 +/- 0.32 days (P > 0.05) in the postoestrus and dioestrus
      queens, respectively. Intermediate cell count averaged 21.43% in dioestrus cats
      and 10.76% in postoestrus cats (P < 0.05). Epithelial cells in the postoestrus
      group had higher cell area, cytoplasm area, cell diameter and cell perimeter
      measurements (P < 0.01). Red (90.9 +/- 1.6), green (76.1 +/- 1.3) and blue (83.6
      +/- 1.4) channel values in postoestrus were higher than the values (81.3 +/- 0.8,
      65.8 +/- 0.9 and 74.0 +/- 0.7, respectively) in dioestrus (P < 0.01). CONCLUSION:
      Induction of ovulation in oestrus queens results in a significant increase in the
      number of intermediate cells and a significant decrease in both the dimensions
      and RGB values of vaginal epithelial cells on day 7.

PMID- 24571341
TI  - Influence of needle gauge used for venipuncture on automated platelet count and
      coagulation profile in dogs.
AB  - OBJECTIVE: To determine if differing gauge (G) needles used for venipuncture
      altered the automated platelet count and coagulation profile (prothrombin time
      (PT) and activated partial thromboplastin time (aPTT)) in clinically healthy
      dogs. DESIGN: Prospective, observational, randomised, clinical study. METHODS: We
      enrolled 20 clinically healthy dogs. Blood was collected via direct venipuncture
      of the jugular veins with 21G, 23G and 25G needles in a random order. Automated
      haematology and automated coagulation times were performed on the blood samples.
      Values were analysed for differences among the needle gauges and also the order
      of sample collection. RESULTS: No difference was found in the automated platelet
      count or automated coagulation times for the three needle gauges used or the
      order in which the samples were collected. CONCLUSION: Venipuncture can be
      performed with a 21G, 23G or 25G needle to obtain blood from dogs for automated
      platelet count and PT/aPTT measurement without affecting the results.

PMID- 24571342
TI  - Corrective osteotomy for procurvatum deformity caused by distal femoral physeal
      fracture malunion stabilised with String-of-Pearls locking plates: results in two
      dogs and a review of the literature.
AB  - BACKGROUND: This report describes the treatment of severe procurvatum because of
      distal femoral physeal fracture malunion in two skeletally immature dogs. CASE
      REPORTS: Both dogs presented with severe right hindlimb lameness and markedly
      reduced stifle extension at less than 5 months of age. Severe distal femoral
      procurvatum and mild-to-moderate femoral shortening secondary to distal femoral
      physeal fracture malunion were evident on radiographs. The sagittal plane
      deformities were addressed with a caudal opening-wedge osteotomy in one dog and
      cranial closing wedge ostectomy in the other dog. String-of-Pearls locking plates
      were used to stabilise the osteotomies. Functional stifle extension range of
      motion and femoral length were improved post surgery in both dogs. Explantation
      of the plates was required in both dogs because of local soft tissue irritation.
      Both dogs had excellent outcomes based on subjective and objective measures
      (pressure sensitive walkway, force platform analysis) when assessed at skeletal
      maturity. CONCLUSIONS: Corrective osteotomy stabilised with String-of-Pearls
      locking plates is a viable treatment option for improving limb function in dogs
      with severe procurvatum deformities caused by distal femoral physeal fracture
      malunion.

PMID- 24571343
TI  - Correction of intramural ureteral ectopia by ureteral transection and
      neoureterostomy with the distal ureter left in situ.
AB  - OBJECTIVE: Retrospective study to determine postoperative continence when
      correcting intramural ureteral ectopia by transection of the ureter and
      neoureterostomy, leaving the distal ureter in situ. We hypothesised that the
      technique would achieve results comparable to previously described surgical
      techniques. METHODS: Medical records for dogs that underwent surgery for
      correction of unilateral intramural ureteral ectopia were reviewed. Cases (n = 9)
      of a neoureterostomy where the distal ureter was left in situ were included.
      Postoperatively, owners were contacted by telephone or email and asked to
      complete a questionnaire, scoring their dog's urinary continence on a scale from
      0 to 2 where 0 was completely continent, 1 was occasional incontinence during
      excitement or while recumbent and 2 was no improvement in postoperative urinary
      continence, with the dog having constantly wet perivulvar fur and constant
      dribbling of urine. RESULTS: All dogs showed signs of severe urinary incontinence
      prior to surgery, including constantly wet perivulvar fur and constant dribbling
      of urine. Postoperatively, six dogs had a score of 0 and three dogs improved to a
      score of 1. Time to follow-up after surgery ranged from 1 to 62 months.
      CONCLUSION: The results of this study support our hypothesis. The technique was
      simple to perform and urinary continence achieved was comparable to that of other
      techniques. We suggest that this technique should be considered as an alternative
      for the correction of intramural ureteral ectopia.

PMID- 24571344
TI  - Diagnostic challenge: Right head tilt and depression in a dog.

PMID- 24571345
TI  - Animal welfare, animal rights.

PMID- 24571346
TI  - Fast nonradiative decay in o-aminophenol.
AB  - The gas phase structure of 2-aminophenol has been investigated using UV-UV as
      well as IR-UV hole burning spectroscopy. The presence of a free OH vibration in
      the IR spectrum rules out the contribution of the cis isomer, which is expected
      to have an intramolecular H-bond, to the spectra. The excited state lifetimes of
      different vibronic levels have been measured with pump-probe picosecond
      experiments and are all very short (35 +/- 5) ps as compared to other substituted
      phenols. The electronic states and active vibrational modes of the cis and trans
      isomers have been calculated with ab initio methods for comparison with the
      experimental spectra. The Franck-Condon simulation of the spectrum using the
      calculated ground and excited state frequencies of the trans isomer is in good
      agreement with the experimental one. The very short excited state lifetime of 2
      aminophenol can then be explained by the strong coupling between the two first
      singlet excited states due to the absence of symmetry, the geometry of the trans
      isomer being strongly nonplanar in the excited state. 

PMID- 24571347
TI  - Process-orientated psychoanalytic work in initial interviews and the importance
      of the opening scene.
AB  - From the very first moment of the initial interview to the end of a long course
      of psychoanalysis, the unconscious exchange between analysand and analyst, and
      the analysis of the relationship between transference and countertransference,
      are at the heart of psychoanalytic work. Drawing on initial interviews with a
      psychosomatically and depressively ill student, a psychoanalytic understanding of
      initial encounters is worked out. The opening scene of the first interview
      already condenses the central psychopathology - a clinging to the primary object
      because it was never securely experienced as present by the patient. The author
      outlines the development of some psychoanalytic theories concerning the initial
      interview and demonstrates their specific importance as background knowledge for
      the clinical situation in the following domains: the 'diagnostic position', the
      'therapeutic position', the 'opening scene', the 'countertransference' and the
      'analyst's free-floating introspectiveness'. More recent investigations refer to
      'process qualities' of the analytic relationship, such as 'synchronization' and
      'self-efficacy'. The latter seeks to describe after how much time between the
      interview sessions constructive or destructive inner processes gain ground in the
      patient and what significance this may have for the decision about the treatment
      that follows. All these factors combined can lead to establishing a differential
      process-orientated indication that also takes account of the fact that being
      confronted with the fear of unconscious processes of exchange is specific to the
      psychoanalytic profession. 

PMID- 24571348
TI  - Protective role of 5-azacytidine on myocardial infarction is associated with
      modulation of macrophage phenotype and inhibition of fibrosis.
AB  - We examined whether a shift in macrophage phenotype could be therapeutic for
      myocardial infarction (MI). The mouse macrophage cell line RAW264.7 was
      stimulated with peptidoglycan (PGN), with or without 5-azacytidine (5AZ)
      treatment. MI was induced by ligation of the left anterior descending coronary
      artery in rats, and the rats were divided into two groups; a saline-injection
      group and a 5AZ-injection group (2.5 mg/kg/day, intraperitoneal injection). LV
      function was evaluated and immunohistochemical analyses were performed 2 weeks
      after MI. Cardiac fibrosis was induced by angiotensin II (AngII) infusion with or
      without 5AZ (5 mg/kg/day) in mice. Nitric oxide was produced by PGN, which was
      reduced by 77.87% after 5AZ treatment. Both induction of inducible nitric oxide
      synthase (iNOS) and iNOS promoter activity by PGN were inhibited by 5AZ. Ejection
      fraction (59.00 +/- 8.03% versus 42.52 +/- 2.58%), contractility (LV dP/dt-max,
      8299.76 +/- 411.56 mmHg versus 6610.36 +/- 282.37 mmHg) and relaxation indices
      (LV dP/dt-min, -4661.37 +/- 210.73 mmHg versus -4219.50 +/- 162.98 mmHg) were
      improved after 5AZ administration. Cardiac fibrosis in the MI+5AZ was 8.14 +/-
      1.00%, compared with 14.93 +/- 2.98% in the MI group (P < 0.05). Arginase
      1(+)CD68(+) macrophages with anti-inflammatory phenotype were predominant in the
      infarct border zone of the MI+5AZ group, in comparison with the MI group. AngII
      induced cardiac fibrosis was also attenuated after 5AZ administration. In cardiac
      fibroblasts, pro-fibrotic mediators and cell proliferation were increased by
      AngII, and these increases were attenuated after 5AZ treatment. 5AZ exerts its
      cardiac protective role through modulation of macrophages and cardiac
      fibroblasts. 

PMID- 24571351
TI  - Two-dimensional solid-state topochemical reactions of 10,12-pentacosadiyn-1-ol
      adsorbed on graphite.
AB  - The photoinduced topochemical reaction of the diacetylene (DA) compound 10,12
      pentacosadiyn-1-ol in the two-dimensional (2D) crystal phase adsorbed on graphite
      was examined by scanning tunneling microscopy (STM). The reaction efficiency and
      the structure of the generated polydiacetylene depend on its polymorphic forms,
      i.e., the "herringbone" or the "parallel" monomer arrangements. The reaction
      efficiency of the herringbone arrangement is lower than that of the parallel
      arrangement because the distance R between the probable reactant acetylenic
      carbon atoms of the herringbone arrangement is longer than that of the parallel
      arrangement. However, the fact that polydiacetylenes form from the herringbone
      arrangement (R = 0.58 nm) is contrary to the geometric criteria for the
      polymerization of three-dimensional (3D) crystals (the reaction was only observed
      if R < 0.4 nm). The polymerization criterion for the 2D phase differs from that
      of the 3D phase. In addition, the STM cross-section profiles of the
      polydiacetylenes reveal that the "lifted-up" and "in-plane" conformations form
      from the parallel and herringbone arrangements, respectively. 

PMID- 24571350
TI  - Laparoscopic hepatectomy for liver metastases from colorectal cancer: a meta
      analysis.
AB  - BACKGROUND: Liver resection can improve long-term survival for liver metastases
      from colorectal cancer. Laparoscopic hepatectomy is gaining increasing
      applications in colorectal liver metastases. We conducted a meta-analysis to
      investigate the safety, feasibility, and efficacy of laparoscopic liver resection
      compared with open hepatectomy for patients with colorectal liver metastases.
      MATERIALS AND METHODS: We performed both database and manual searching for
      comparative studies published before June 2013 without language or region
      restriction. Outcomes of interest consisted of perioperative outcomes and
      oncologic outcomes. RESULTS: Seven observational studies including 624 patients
      (241 in the laparoscopic group, 383 in the open group) were included. No
      randomized controlled trials were available. Pooled long-term oncologic outcomes
      of overall survival (hazard ratio=0.844; 95% confidence interval [CI] 0.412,
      1.730; P=.644; I(2)=80.6%) and disease-free survival (hazard ratio=1.234; 95% CI
      0.652, 2.333; P=.518; I(2)=79.6%) were similar in both groups. Subgroup analyses
      of studies with high quality and homogeneity confirmed the above outcomes.
      However, a lower incidence of R1 resection was observed in the laparoscopic group
      (relative risk [RR]=0.357; 95% CI 0.180, 0.708; P=.003; I(2)=0.0%) than in the
      open group. As for perioperative outcomes, laparoscopic hepatectomy presented a
      lower occurrence of postoperative complications (RR=0.647; 95% CI 0.477, 0.877;
      P=.005; I(2)=0.0%) and similar mortality (RR=0.625; 95% CI 0.12, 3.25; P=.576;
      I(2)=0.0%); less blood loss and less need for transfusion were also found in
      laparoscopic patients, whereas comparable operative time and length of hospital
      stay were required in the two groups. CONCLUSIONS: Laparoscopic hepatectomy is a
      safe procedure for colorectal liver metastases with long-term survival comparable
      to that of open hepatectomy. More prospective studies with adequate subgroup
      analyses are awaited to construct defined criteria for patient selection. Future
      randomized controlled trials are needed to eliminate potential selection bias and
      to confirm this conclusion.

PMID- 24571349
TI  - Immunochromatographic diagnostic test analysis using Google Glass.
AB  - We demonstrate a Google Glass-based rapid diagnostic test (RDT) reader platform
      capable of qualitative and quantitative measurements of various lateral flow
      immunochromatographic assays and similar biomedical diagnostics tests. Using a
      custom-written Glass application and without any external hardware attachments,
      one or more RDTs labeled with Quick Response (QR) code identifiers are
      simultaneously imaged using the built-in camera of the Google Glass that is based
      on a hands-free and voice-controlled interface and digitally transmitted to a
      server for digital processing. The acquired JPEG images are automatically
      processed to locate all the RDTs and, for each RDT, to produce a quantitative
      diagnostic result, which is returned to the Google Glass (i.e., the user) and
      also stored on a central server along with the RDT image, QR code, and other
      related information (e.g., demographic data). The same server also provides a
      dynamic spatiotemporal map and real-time statistics for uploaded RDT results
      accessible through Internet browsers. We tested this Google Glass-based
      diagnostic platform using qualitative (i.e., yes/no) human immunodeficiency virus
      (HIV) and quantitative prostate-specific antigen (PSA) tests. For the
      quantitative RDTs, we measured activated tests at various concentrations ranging
      from 0 to 200 ng/mL for free and total PSA. This wearable RDT reader platform
      running on Google Glass combines a hands-free sensing and image capture interface
      with powerful servers running our custom image processing codes, and it can be
      quite useful for real-time spatiotemporal tracking of various diseases and
      personal medical conditions, providing a valuable tool for epidemiology and
      mobile health. 

PMID- 24571352
TI  - Hidden or uninvited? A content analysis of elder LGBT of color literature in
      gerontology.
AB  - As longevity increases and marginalized communities achieve greater visibility in
      the United States, a content analysis of 64 articles in social work, health,
      medicine and nursing, and gerontology/psychology examined the extent to which the
      literature examines the needs and concerns of lesbian, gay, bisexual, and
      transgender (LGBT) seniors of color (SOC). We found recognition of the distinct
      cultural needs of sexual orientation and gender minorities. However the
      distinctive needs of LGBT SOC remains underexplored and poorly documented.
      Gerontologists, social workers, policymakers, and advocates must support research
      that values the experience and multiple vulnerabilities of LGBT seniors and
      questions the structures preventing inclusion and participation. 

PMID- 24571353
TI  - Covalent attachment of mechanoresponsive luminescent micelles to glasses and
      polymers in aqueous conditions.
AB  - Covalent attachment of mechanoresponsive luminescent organic or organometallic
      compounds to other materials is a promising approach to develop a wide variety of
      mechanoresponsive luminescent materials. Here, we report covalently linkable
      mechanoresponsive micelles that change their photoluminescence from yellow to
      green in response to mechanical stimulation under aqueous conditions. These
      micelles are composed of a dumbbell-shaped amphiphilic pyrene derivative having
      amine groups at the peripheral positions of its dendrons. Using a well
      established cross-linker, the micelles were covalently linked via their
      peripheral amine groups to the surface of glass beads, polylactic acid (PLA)
      beads, and living cells under aqueous conditions. Vortexing of glass beads
      bearing the micelles in a glass vial filled with water caused a photoluminescence
      color change from yellow to green. PLA beads bearing the micelles showed no
      change in photoluminescence color under the same conditions. We ascribe this
      result to the lower density and stiffness of the PLA beads, because the color of
      the PLA beads changed on vortexing in the presence of bare glass beads. HeLa
      cells and HL-60 cells bearing the micelles showed no obvious photoluminescence
      color change under vortexing. The structure, photophysical properties, and
      mechanism of photoluminescence color change of the micellar assemblies were
      examined. 

PMID- 24571354
TI  - Emerging evidence on the crystalline water-light interface in ophthalmology and
      therapeutic implications in photobiomodulation: first communication.
AB  - OBJECTIVE: The purpose of this study was to present preliminary evidence of the
      exclusion zone (EZ) and photobiomodulation (PBM) phenomena relating to
      ophthalmology. BACKGROUND DATA: Water is the main media and fluid found in ocular
      tissues. Water is also an important photoacceptor and energy storage medium. Eyes
      are abundantly exposed to environmental radiant energy. Therefore, multiple light
      energy-absorption mechanisms may exist, including those associated with the
      recently discovered fourth phase of water, known as EZ. METHODS: Retrospective
      analysis of published data indicative of EZ phenomena related, in this first
      communication, to the retina and optic nerve (ON), using surgical microscopy and
      diffusion-weighted magnetic resonance imaging (MRI). RESULTS: Images showing
      removal of the internal limiting membrane (ILM) aided by preservative-free
      triamcinolone acetonide (TA) during macular hole surgery show continuous whitish
      lines indicative of water-layer ordering at the interface between collagen
      matrices and TA crystals. Apparent diffusion coefficient (ADC) results further
      exhibit an axis parallel to the ON, which may be an ocular expression of the EZ
      linked to the steady potential of the eye. CONCLUSIONS: Although existing results
      are still being decoded and analyzed in light of the state of the art studies of
      light-water interactions, they suggest a new understanding of the eye's
      bioenergetic environment, which may have deep implications in ocular physiology
      as well as in the pathophysiology, diagnosis, and treatment of blinding diseases
      using light-based therapies such as photobiomodulation. Research is needed to
      confirm the interpretation of these findings and validate potential ophthalmic
      applications.

PMID- 24571355
TI  - The risk of asthma exacerbation after reducing inhaled corticosteroids: a
      systematic review and meta-analysis of randomized controlled trials.
AB  - BACKGROUND: Asthma guidelines suggest reducing controller medications when asthma
      is stable. METHODS: The purpose of the study is to estimate the risk of asthma
      exacerbation in stable asthmatics who reduce inhaled corticosteroids (ICS)
      compared to those who maintain a stable ICS dose. We identified articles from a
      systematic review of English and non-English articles using MEDLINE, EMBASE, Web
      of Science, and CENTRAL (inception to May 25, 2013). We included randomized
      controlled trials (RCTs) with a stable asthma run-in period of 4 weeks or more,
      an intervention to reduce ICS, and a follow-up period of at least 3 months.
      RESULTS: The search strategy identified 2253 potential articles, of which 206
      were reviewed at the full-text level and 6 met criteria for inclusion. The
      relative risk of an asthma exacerbation in individuals who reduced ICS compared
      to those who maintained the same ICS dose was 1.25 (95% CI 0.96, 1.62; P = 0.10;
      I(2)  = 0%) in studies with a mean follow-up of 22 weeks. Individuals who reduced
      ICS had a decreased% predicted FEV1 of 0.87% (95% CI -1.58%,3.33%; P = 0.49, I(2)
      = 58%) and a decreased mean morning peak expiratory flow of 9.57 l/min (95% CI
      1.25, 17.90; P = 0.02; I(2)  = 74%) compared to those individuals who maintained
      a stable ICS dose. CONCLUSIONS: Asthma exacerbations were statistically no more
      likely among individuals who reduced ICS compared to those who maintained their
      ICS dose, supporting current guidelines which recommend decreasing ICS by 50%
      after a period of asthma stability.

PMID- 24571356
TI  - Time to death analysis of road traffic accidents in relation to delta V, drunk
      driving, and restraint systems.
AB  - OBJECTIVE: The main goal of this research is to identify variables related to the
      expected time to death due to road traffic accidents (RTAs). Such research is
      expected to be useful in improving safety laws and regulations and developing new
      safety systems. The resulting information is crucial not only for reducing
      accident fatalities but for assessing related insurance policies. METHODS: In
      this article, we analyze factors that are potentially associated with variation
      in the expected survival time after a road traffic accident using Weibull
      regression. In particular, we consider the association with alcohol involvement,
      delta V, and restraint systems. RESULTS: Our empirical results, obtained based on
      the NASS-CDS, indicate that the expected survival time for non-alcohol-impaired
      drivers is 3.23 times longer at a delta V of 50 km/h than that for alcohol
      impaired drivers under the same conditions. In addition, it was observed that,
      even when occupants were alcohol-impaired, if they were protected by both air
      bags and seat belts, their expected survival time after an RTA increased 2.59
      fold compared to alcohol-impaired drivers who used only seat belts. CONCLUSION:
      Our findings may be useful in improving road traffic safety and insurance
      policies by offering insights into the factors that reduce fatalities.

PMID- 24571357
TI  - Histone H3K9 and H3K27 methylation regulates fungal alkaloid biosynthesis in a
      fungal endophyte-plant symbiosis.
AB  - Epichloe festucae is a filamentous fungus that forms a mutually beneficial
      symbiotic association with Lolium perenne. This endophyte synthesizes
      bioprotective lolitrems (ltm) and ergot alkaloids (eas) in planta but the
      mechanisms regulating expression of the corresponding subtelomeric gene clusters
      are not known. We show here that the status of histone H3 lysine 9 and lysine 27
      trimethylation (H3K9me3/H3K27me3) at these alkaloid gene loci are critical
      determinants of transcriptional activity. Using ChIP-qPCR we found that levels of
      H3K9me3 and H3K27me3 were reduced at these loci in plant infected tissue compared
      to axenic culture. Deletion of E. festucae genes encoding the H3K9- (ClrD) or
      H3K27- (EzhB) methyltransferases led to derepression of ltm and eas gene
      expression under non-symbiotic culture conditions and a further enhancement of
      expression in the double deletion mutant. These changes in gene expression were
      matched by corresponding reductions in H3K9me3 and H3K27me3 marks. Both
      methyltransferases are also important for the symbiotic interaction between E.
      festucae and L. perenne. Our results show that the state of H3K9 and H3K27
      trimethylation of E. festucae chromatin is an important regulatory layer
      controlling symbiosis-specific expression of alkaloid bioprotective metabolites
      and the ability of this symbiont to form a mutualistic interaction with its host.

PMID- 24571358
TI  - The occurrence of giant fibres in different muscles of two chicken genotypes.
AB  - 1. The occurrence of Giant Fibres (GF) in three muscles (Pectoralis major (PM),
      Iliotibialis lateralis and Semimembranosus) with different types of energy
      metabolism was studied in slow- and fast-growing chicken strains. 2. A total of
      20 one-day-old Leghorn chicks (slow-growing) and 20 broiler (Ross 508) chicks
      (fast-growing) were reared to 100 and 45 d, respectively. 3. A small percentage
      of GF was seen in pre rigor muscle samples even at 3 min post mortem in both
      genotypes and in all muscle types studied. 4. From 3 min to 24 h post mortem GF
      increased both in Leghorn and broiler chickens but to a different extent
      according to muscle type and genotype. 5. The highest GF 24 h post mortem value
      was found in the PM muscles belonging to the fast-growing broiler line. 6. It was
      concluded that every type of muscle can develop GF, but this phenomenon is more
      evident in the PM especially in animals selected for increased growth rate.

PMID- 24571359
TI  - Current status and effectiveness of mentorship programmes in urology: a
      systematic review.
AB  - The objectives of this review were to identify and evaluate the efficacy of
      mentorship programmes for minimally invasive procedures in urology and give
      recommendations on how to improve mentorship. A systematic literature search of
      the PubMed/Medline databases was carried out according to the Preferred Reporting
      Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. In all, 21
      articles were included in the review and divided into four categories:
      fellowships, mini-fellowships, mentored skills courses and novel mentorship
      programmes. Various structures of mentorship programme were identified and in
      general, mentorship programmes were found to be feasible, having content validity
      and educational impact. Perioperative data showed equally good outcomes when
      comparing trainees and specialists. Mentorship programmes are effective and
      represent one of the best current methods of training in urology. However,
      participation in such programmes is not widespread. The structure of mentorship
      programmes is highly variable, with no clearly defined 'best approach' for
      postgraduate training. This review offers recommendations as to how this 'best
      approach' can be established. 

PMID- 24571360
TI  - Resveratrol attenuates NF-kappaB-binding activity but not cytokine production in
      mechanically ventilated mice.
AB  - BACKGROUND: Mechanical ventilation (MV) can result in inflammation and subsequent
      lung injury. Toll-like receptor (TLR)4 and NF-kappaB are proposed to play a
      crucial role in the MV-induced inflammatory response. Resveratrol (RVT) exhibits
      anti-inflammatory effects in vitro and in vivo supposedly by interfering with
      TLR4 signaling and NF-kappaB. In the present study, we investigated the role of
      RVT in MV-induced inflammation in mice. METHODS: RVT (10 mg/kg, 20 mg/kg and 40
      mg/kg) or vehicle was intraperitoneally administered 1 h before start of MV (4 h,
      tidal volume 8 ml/kg, positive end-expiratory pressure 1,5 cmH2 O and FiO2 0.4).
      Blood and lungs were harvested for cytokine analysis. DNA binding activity of
      transcription factor NF-kappaB was measured in lung homogenates. RESULTS: MV
      resulted in elevated pulmonary concentrations of IL-1beta, IL-6, keratinocyte
      derived chemokine (KC) and NF-kappaB DNA-binding activity. RVT at 10, 20 and 40
      mg/kg reduced NF-kappaB's DNA-binding activity following MV compared with
      ventilated controls. However, no differences in cytokine release were found
      between RVT-treated and control ventilated mice. Similarly, in plasma, MV
      resulted in elevated concentrations of TNF-alpha, KC and IL-6, but RVT did not
      affect cytokine levels. CONCLUSIONS: RVT abrogates the MV-induced increase in
      pulmonary NF-kappaB activity but does not attenuate cytokine levels. This implies
      a less prominent role for NF-kappaB in MV-induced inflammation than previously
      assumed.

PMID- 24571361
TI  - Scavenging of organic C-centered radicals by nitroxides.

PMID- 24571363
TI  - Will different OTU delineation methods change interpretation of arbuscular
      mycorrhizal fungal community patterns?

PMID- 24571362
TI  - Diagnostic accuracy of a point-of-care urine test for tuberculosis screening
      among newly-diagnosed HIV-infected adults: a prospective, clinic-based study.
AB  - BACKGROUND: A rapid diagnostic test for active tuberculosis (TB) at the clinical
      point-of-care could expedite case detection and accelerate TB treatment
      initiation. We assessed the diagnostic accuracy of a rapid urine
      lipoarabinomannan (LAM) test for TB screening among HIV-infected adults in a TB
      endemic setting. METHODS: We prospectively enrolled newly-diagnosed HIV-infected
      adults (>=18 years) at 4 outpatient clinics in Durban from Oct 2011-May 2012,
      excluding those on TB therapy. A physician evaluated all participants and offered
      CD4 cell count testing. Trained study nurses collected a sputum sample for acid
      fast bacilli smear microscopy (AFB) and mycobacterial culture, and performed
      urine LAM testing using DetermineTM TB LAM in the clinic. The presence of a band
      regardless of intensity on the urine LAM test was considered positive. We defined
      as the gold standard for active pulmonary TB a positive sputum culture for
      Mycobacterium tuberculosis. Diagnostic accuracy of urine LAM was assessed, alone
      and in combination with smear microscopy, and stratified by CD4 cell count.
      RESULTS: Among 342 newly-diagnosed HIV-infected participants, 190 (56%) were
      male, mean age was 35.6 years, and median CD4 was 182/mm3. Sixty participants had
      culture-positive pulmonary TB, resulting in an estimated prevalence of 17.5% (95%
      CI 13.7-22.0%). Forty-five (13.2%) participants were urine LAM positive. Mean
      time from urine specimen collection to LAM test result was 40 minutes (95% CI 34
      46 minutes). Urine LAM test sensitivity was 28.3% (95% CI 17.5-41.4) overall, and
      37.5% (95% CI 21.1-56.3) for those with CD4 count <100/mm3, while specificity was
      90.1% (95% CI 86.0-93.3) overall, and 86.9% (95% CI 75.8-94.2) for those with CD4
      < 100/mm3. When combined with sputum AFB (either test positive), sensitivity
      increased to 38.3% (95% CI 26.0-51.8), but specificity decreased to 85.8% (95% CI
      81.1-89.7). CONCLUSIONS: In this prospective, clinic-based study with trained
      nurses, a rapid urine LAM test had low sensitivity for TB screening among newly
      diagnosed HIV-infected adults, but improved sensitivity when combined with sputum
      smear microscopy.

PMID- 24571365
TI  - Use of groundwater levels with the PULSE analytical model.
AB  - The PULSE analytical model, which calculates daily groundwater discharge on the
      basis of user-specified recharge, was originally developed for calibration using
      streamflow data. This article describes a model application in which groundwater
      level data constitute the primary control on model input. As a test case, data
      were analyzed from a small basin in central Pennsylvania in which extensive
      groundwater level data are available. The timing and intensity of daily water
      level rises are used to ascertain temporal distribution of recharge, and the
      simulated groundwater discharge hydrograph has shape features that are similar to
      the streamflow hydrograph. This article does not include details about
      calibration, but some steps are illustrated and general procedures are described
      for calibration in specific hydrologic studies. The PULSE model can be used to
      assess results of fully automated base flow methods and can be used to define
      groundwater recharge and discharge at a relatively small time scale. 

PMID- 24571364
TI  - Improved intensity-based label-free quantification via proximity-based intensity
      normalization (PIN).
AB  - Researchers are increasingly turning to label-free MS1 intensity-based
      quantification strategies within HPLC-ESI-MS/MS workflows to reveal biological
      variation at the molecule level. Unfortunately, HPLC-ESI-MS/MS workflows using
      these strategies produce results with poor repeatability and reproducibility,
      primarily due to systematic bias and complex variability. While current global
      normalization strategies can mitigate systematic bias, they fail when faced with
      complex variability stemming from transient stochastic events during HPLC-ESI
      MS/MS analysis. To address these problems, we developed a novel local
      normalization method, proximity-based intensity normalization (PIN), based on the
      analysis of compositional data. We evaluated PIN against common normalization
      strategies. PIN outperforms them in dramatically reducing variance and in
      identifying 20% more proteins with statistically significant abundance
      differences that other strategies missed. Our results show the PIN enables the
      discovery of statistically significant biological variation that otherwise is
      falsely reported or missed. 

PMID- 24571366
TI  - Smoking behaviours of adolescents, influenced by smoking of teachers, family and
      friends.
AB  - BACKGROUND: Smoking tobacco is a global health problem, and this study highlights
      adolescent smoking in Taiwan. Smoking was completely banned on campuses under the
      Tobacco Hazards Prevention Act and School Health Regulations. Few have
      investigated the association between personnel smoking/school smoking policies
      and adolescent smoking in Taiwan. The smoking rate has gradually increased for
      senior high school students in Taiwan from 10.7% in 1994 to 14.7% in 2011. AIM:
      This study examined the influence of family and friends' smoking on the
      association between the presence of teachers smoking and each stage of
      adolescents' smoking behaviour. METHODS: A cross-sectional survey was conducted
      in nine high schools (n = 921). Logistic regression analysis was used to examine
      the association between smoking stage, father smoking, mother smoking, sibling
      smoking, friends smoking and the presence of smoking teachers. RESULTS: After
      adjusting for gender, school type and grade, fathers', siblings' and friends'
      smoking were significantly associated with adolescents' ever and current smoking
      behaviours, but mothers' smoking was only associated with adolescents' current
      smoking behaviours. Friends' smoking was strongly associated with being a smoker.
      While there was an interaction between friends' smoking and the presence of
      smoking teachers on current smoking behaviours indicating the effect of the
      presence of smoking teachers was increased when friends did not smoke.
      DISCUSSION: The results suggest that teachers smoking on school may increase the
      likelihood of being a current smoker as their friends do not smoke. Family and
      friends smoking are associated with adolescent smoking. CONCLUSION: The Taiwanese
      government has regulated a comprehensive smoking ban in schools to prohibit both
      student and staff smoking on all school premises. To achieve this, schools should
      make tobacco control communication efforts. Nurses could address the combined
      influence of family and friends as well as the effect of school smoking
      restrictions to help prevent adolescents from smoking.

PMID- 24571368
TI  - Characterization of the hydrides in Stryker's reagent: [HCu{P(C6H5)3}]6.
AB  - A structural, spectroscopic, and computational investigation of Stryker's
      reagent, [HCu{P(C6H5)3}]6, and its isotopomers has provided new insights into the
      complex. Neutron diffraction shows that the hydrides are best described as edge
      bridging rather than face bridging. The combination of infrared and inelastic
      neutron scattering spectroscopies has allowed the location of most of the modes
      associated with the hydrides and their assignments. The structural and
      spectroscopic conclusions are supported by the ab initio studies of the complex. 

PMID- 24571369
TI  - Subtle charge balance controls surface-nucleated self-assembly of designed
      biopolymers.
AB  - We report the surface-nucleated self-assembly into fibrils of a biosynthetic
      amino acid polymer synthesized by the yeast Pichia pastoris. This polymer has a
      block-like architecture, with a central silk-like block labeled SH, responsible
      for the self-assembly into fibrils, and two collagen-like random coil end blocks
      (C) that colloidally stabilize the fibers in aqueous solution. The silk-like
      block contains histidine residues (pKa~6) that are positively charged in the low
      pH region, which hinders self-assembly. In aqueous solution, CSHC self-assembles
      into fibers above a pH-dependent critical nucleation concentration Ccb. Below
      Ccb, where no self-assembly occurs in solution, fibril formation can be induced
      by a negatively charged surface (silica) in the pH range of 3.5-7. The density of
      the fibers at the surface and their length are controlled by a subtle balance in
      charge between the protein polymer and the silica surface, which is evidenced
      from the dependence on pH. With increasing number density of the fibers at the
      surface, their average length decreases. The results can be explained on the
      basis of a nucleation-and-growth mechanism: the surface density of fibers depends
      on the rate of nucleation, while their growth rate is limited by transport of
      proteins from solution. Screening of the charges on the surface and histidine
      units by adding NaCl influences the nucleation-and-growth process in a
      complicated fashion: at low pH, the growth is improved, while at high pH, the
      nucleation is limited. Under conditions where nucleation in the bulk solution is
      not possible, growth of the surface-nucleated fibers into the solution--away from
      the surface--can still occur.

PMID- 24571367
TI  - What's loneliness got to do with it? Older women who use benzodiazepines.
AB  - AIM: We examined qualitative data from a larger study of benzodiazepine-using
      women older than 65 years, living in the United States, for subjective
      experiences of loneliness and social isolation. METHOD: Data from semistructured
      interviews with seven participants discussed aspects of social isolation or
      loneliness. Following a phenomenological design, data were coded and analysed for
      experiences. RESULTS: Three themes emerged: 'Dislike being alone'; 'Loneliness
      and isolation'; and 'Social isolation causes negative feelings'. CONCLUSION:
      Social isolation and loneliness are negative aspects of the lived experience for
      older benzodiazepine-using women and the loss of companions and transportation is
      important to this experience. Being isolated can cause depression, fear and
      insecurity. Future research should consider the role psychotropic medications
      have in coping with social isolation and loneliness among older adults.
      Clinicians should be aware of social isolation and loneliness in late life and
      discuss non-pharmacologic treatment options with their ageing patients.

PMID- 24571370
TI  - Analysis of pulp prognosis in 603 permanent teeth with uncomplicated crown
      fracture with or without luxation.
AB  - AIM: To analyze the pulp prognosis of uncomplicated crown-fractured teeth with or
      without concurrent luxation injury in adolescent. MATERIAL AND METHODS: Complete
      dental records of traumatized permanent teeth were obtained, including the
      patient's name, gender and age, position of the traumatized tooth, its stage of
      root development, time elapsed between dental injury and treatment, diagnosis,
      clinical procedures, and follow-up period. Pulp prognosis was evaluated over a
      period of at least 6 months using Andreasen's classification. Kaplan-Meier method
      and Cox regression were used to examine the risk factors inherent to the
      prognosis of pulp healing, with P < 0.05 accepted as statistically significant.
      RESULTS: The study involved 603 teeth with uncomplicated crown fractures followed
      up for 6 months or longer, of which 104 suffered luxation at the same time. The
      frequency of pulp necrosis in teeth with complete root development was higher
      than those with incomplete root development. For uncomplicated crown fracture
      with luxation, crown-fractured teeth with intrusion had a higher incidence of
      pulp necrosis than other types of concurrent luxation (OR: 33.613). The incidence
      of pulp necrosis within 3 months was significantly higher than in other time
      periods (P = 0.021), and the median survival time was 53 days (95% confidence
      interval: 34-67 days). CONCLUSIONS: Existence of concurrent luxation injury and
      complete root development are important risk factors of pulp necrosis in teeth
      with uncomplicated crown fractures in adolescent.

PMID- 24571371
TI  - Arachidonic acid metabolites and enzyme transcripts in asthma are altered by
      cigarette smoking.
AB  - BACKGROUND: Arachidonic acid metabolites are implicated in the pathogenesis of
      asthma although only limited information is available on the impact of current
      smoking history on these metabolites. The aim of the study was to examine the
      effect of smoking status on urinary, sputum, and plasma eicosanoid concentrations
      and relevant enzyme transcripts in asthma. METHODS: In 108 smokers and never
      smokers with asthma and 45 healthy controls [smokers and never smokers], we
      measured urinary tetranor prostaglandin (PG)D2 (PGDM) and leukotriene (LT)E4 ,
      induced sputum fluid LTB4 , LTE4 , PGD2 , and PGE2 , plasma secretory
      phospholipase A2 (sPLA2 ), and 11beta prostaglandin F2alpha (11betaPGF2alpha ),
      and, in a subgroup with severe asthma, airway leukocyte and epithelial cell mRNA
      expression levels of arachidonic acid metabolic enzymes. RESULTS: Smokers with
      asthma had higher urinary LTE4 ; 83 (59, 130) vs 59 (40, 90) pg/mg creatinine, P
      = 0.008, and PGDM; 60 (35, 100) vs 41 (28, 59) ng/mg creatinine, P = 0.012
      concentrations, respectively, and lower sputum PGE2 concentrations 80 (46, 157)
      vs 192 (91, 301) pg/ml, P = 0.001 than never smokers with asthma. Sputum LTB4 (P
      = 0.013), and plasma 11betaPGF2alpha (P = 0.032), concentrations, respectively,
      were increased in smokers with asthma compared with healthy smokers. Asthma
      specific and smoking-related increases (>1.5-fold expression) in arachidonate 15
      lipoxygenase and gamma-glutamyltransferase transcripts were demonstrated.
      CONCLUSIONS: Several arachidonic acid metabolites and enzyme transcripts
      involving both lipoxygenase and cyclooxygenase pathways are increased in smokers
      with asthma and differ from never smokers with asthma. Possibly targeting
      specific lipoxygenase and cyclooxygenase pathways that are activated by asthma
      and cigarette smoking may optimize therapeutic responses.

PMID- 24571373
TI  - Boron trifluoride etherate functioning as a fluorine source in an iodosobenzene
      mediated intramolecular aminofluorination of homoallylic amines.
AB  - A widely used Lewis acid BF3.Et2O was shown to be capable of acting as an
      efficient fluorinating agent in an intramolecular aminofluorination reaction of
      homoallylic amines to provide 3-fluoropyrrolidines mediated by a commercially
      available hypervalent iodine(III) reagent PhIO at room temperature. A mechanism
      involving a carbocation intermediate was proposed on the basis of several
      experimental evidence. 

PMID- 24571372
TI  - Modeling the impact of hepatitis C viral clearance on end-stage liver disease in
      an HIV co-infected cohort with targeted maximum likelihood estimation.
AB  - Despite modern effective HIV treatment, hepatitis C virus (HCV) co-infection is
      associated with a high risk of progression to end-stage liver disease (ESLD)
      which has emerged as the primary cause of death in this population. Clinical
      interest lies in determining the impact of clearance of HCV on risk for ESLD. In
      this case study, we examine whether HCV clearance affects risk of ESLD using data
      from the multicenter Canadian Co-infection Cohort Study. Complications in this
      survival analysis arise from the time-dependent nature of the data, the presence
      of baseline confounders, loss to follow-up, and confounders that change over
      time, all of which can obscure the causal effect of interest. Additional
      challenges included non-censoring variable missingness and event sparsity. In
      order to efficiently estimate the ESLD-free survival probabilities under a
      specific history of HCV clearance, we demonstrate the double-robust and
      semiparametric efficient method of Targeted Maximum Likelihood Estimation (TMLE).
      Marginal structural models (MSM) can be used to model the effect of viral
      clearance (expressed as a hazard ratio) on ESLD-free survival and we demonstrate
      a way to estimate the parameters of a logistic model for the hazard function with
      TMLE. We show the theoretical derivation of the efficient influence curves for
      the parameters of two different MSMs and how they can be used to produce variance
      approximations for parameter estimates. Finally, the data analysis evaluating the
      impact of HCV on ESLD was undertaken using multiple imputations to account for
      the non-monotone missing data. 

PMID- 24571374
TI  - Morphology and molecular phylogeny of a new haptorian ciliate, Chaenea mirabilis
      sp. n., with implications for the evolution of the dorsal brush in haptorians
      (Ciliophora, Litostomatea).
AB  - We discovered a new haptorian ciliate, Chaenea mirabilis sp. n., in brackish
      water collected near the town of Busan, Korea. Its morphology was studied using
      standard taxonomical methods and its phylogenetic relationships were assessed by
      phylogenetic analysis of the 18S rRNA gene. Chaenea mirabilis is distinguished
      from all congeners by the combination of the following traits: (i) a narrowly
      bursiform to flask-shaped, 60-100 MUm long body; (ii) 11-21 doughnut-shaped or
      sometimes horseshoe-shaped macronuclear nodules; (iii) two types of extrusomes:
      type I is rod-shaped and 6-8 MUm long, while type II is narrowly to broadly
      teardrop-shaped and only 1.5-2 MUm long; (iv) highly refractive special granules
      tightly arranged between the first and second brush row, forming a conspicuous
      bulge; and (v) 12-13 somatic kineties. In the 18S rRNA gene phylogeny, C.
      mirabilis clustered with full support with other congeners. However, there was no
      statistical support for classification of Chaenea into the families Fuscheriidae,
      Acropisthiidae, or Trachelophyllidae, but a sister relationship with the
      Lacrymariidae could not be excluded. Therefore, we establish a new family,
      Chaeneidae, within the order Lacrymariida. This affiliation is strongly
      corroborated by the distinctly subapical dorsal brush bearing cilium-like
      bristles.

PMID- 24571375
TI  - Novel smart yolk/shell polymer microspheres as a multiply responsive cargo
      delivery system.
AB  - An effective strategy was developed to fabricate the novel dually thermo- and pH
      responsive yolk/shell polymer microspheres as a drug delivery system (DDS) for
      the controlled release of anticancer drugs via two-stage distillation
      precipitation polymerization and seed precipitation polymerization. Their pH
      induced thermally responsive polymer shells act as a smart "valve" to adjust the
      diffusion of the loaded drugs in/out of the polymer containers according to the
      body environments, while the movable P(MAA-co-EGDMA) cores enhance the drug
      loading capacity for the anticancer drug doxorubicin hydrochloride (DOX). The
      yolk/shell polymer microspheres show a low leakage at high pH values but
      significantly enhanced release at lower pH values equivalent to the tumor body
      fluid environments at human body temperature, exhibiting the apparent tumor
      environment-responsive controlled "on-off" drug release characteristics.
      Meanwhile, the yolk/shell microspheres expressed very low in vitro cytotoxicity
      on HepG2 cells. Consequently, their precise tumor-environment-responsive drug
      delivery performance and high drug loading capacity offer promise for tumor
      therapy. 

PMID- 24571376
TI  - Polytomous multilevel testlet models for testlet-based assessments with complex
      sampling designs.
AB  - Applications of standard item response theory models assume local independence of
      items and persons. This paper presents polytomous multilevel testlet models for
      dual dependence due to item and person clustering in testlet-based assessments
      with clustered samples. Simulation and survey data were analysed with a
      multilevel partial credit testlet model. This model was compared with three
      alternative models - a testlet partial credit model (PCM), multilevel PCM, and
      PCM - in terms of model parameter estimation. The results indicated that the
      deviance information criterion was the fit index that always correctly identified
      the true multilevel testlet model based on the quantified evidence in model
      selection, while the Akaike and Bayesian information criteria could not identify
      the true model. In general, the estimation model and the magnitude of item and
      person clustering impacted the estimation accuracy of ability parameters, while
      only the estimation model and the magnitude of item clustering affected the item
      parameter estimation accuracy. Furthermore, ignoring item clustering effects
      produced higher total errors in item parameter estimates but did not have much
      impact on the accuracy of ability parameter estimates, while ignoring person
      clustering effects yielded higher total errors in ability parameter estimates but
      did not have much effect on the accuracy of item parameter estimates. When both
      clustering effects were ignored in the PCM, item and ability parameter estimation
      accuracy was reduced. 

PMID- 24571377
TI  - Nurses, formerly incarcerated adults, and Gadamer: phronesis and the Socratic
      dialectic.
AB  - This paper describes the first phase of an ongoing education and research project
      guided by three main intentions: (1) to create opportunities for phronesis in the
      classroom; (2) to develop new understandings about phronesis as it relates to
      nursing care generally and to caring for specific groups, like formerly
      incarcerated adults; and (3) to provide an opportunity for formerly incarcerated
      adults and graduate nursing students to participate in a dialectical conversation
      about ethical knowing. Gadamer's writings on practical philosophy, phronesis, and
      the Socratic dialectic provide the philosophical foundation and framework for the
      project. The first phase in the project was a 4-h class within a graduate-level
      health promotion course during which 30 nursing students and three formerly
      incarcerated panelists engaged in a dialectic conversation about what it means to
      care for formerly incarcerated adults in a meaningful way. After the class, two
      focus groups were conducted, one with the students and one with the formerly
      incarcerated panelists. Findings articulated participants' prejudices and
      assumptions prior to the class, expanded sense of phronesis, and ability to
      consider nursing practice within a larger ethical framework. Panelists and
      students left the class with a deeper understanding of one another and expressed
      an openness towards continued dialectic conversations together. Use of the
      Socratic dialectic within nursing curricula reflects a current and critical trend
      in nursing education to bring non-epistemologic forms of knowledge into the
      classroom. 

PMID- 24571378
TI  - Outcomes of simultaneous laparoscopic colorectal and hepatic resection for
      patients with colorectal cancers: a comparative study.
AB  - BACKGROUND: Although laparoscopic colorectal resection and laparoscopic liver
      resection have been accepted as effective alternatives to conventional open
      procedures, there are only a few reports on the clinical availability of
      simultaneous performance of these two procedures. We report our collective
      experience of patients with colorectal cancers treated with totally laparoscopic
      colorectal and liver resection, in comparison with those treated with an open
      approach. PATIENTS AND METHODS: This study is a retrospective, case-match review
      of prospectively collected data. Between May 2008 and December 2012, 24 patients
      with primary colorectal cancer and associated hepatic lesions underwent
      simultaneous laparoscopic colorectal and liver resection (laparoscopic group).
      They were matched with patients who underwent an open procedure (open group; n=24
      out of 232) based on the types of surgery. Patient demographics, operative
      details, tumor-related parameters, and postoperative outcomes were analyzed.
      RESULTS: Demographic features and pathologic outcomes were similar in both
      groups. The median duration of operation was significantly longer in the
      laparoscopic group than in the open group (290 versus 244 minutes; P=.008), and
      the median estimated blood loss was larger (325 versus 250 mL; difference not
      significant, P=.35). However, the time to starting a soft blended diet (3.0
      versus 4.5 days; P<.001) and postoperative stay (8.0 versus 10.5 days; P=.001) in
      the laparoscopic group were both significantly shorter than in the open group.
      The postoperative complication rate was lower in the laparoscopic group (17%
      versus 42%; difference not significant, P=.06). The minor complication rate was
      significantly lower in the laparoscopic group (4% versus 33%; P=.02).
      CONCLUSIONS: A totally laparoscopic approach might provide short-term benefits
      associated with enhanced postoperative recovery despite a longer procedure time
      and larger blood loss. It can be a reasonable option for simultaneous colorectal
      and hepatic resection.

PMID- 24571379
TI  - Aneuploidy frequency in spermatozoa of Egyptian men with normal and abnormal
      semen parameters using fluorescence in situ hybridisation.
AB  - Chromosome anomalies were suggested to be more frequent in infertile males so our
      case-control study aimed at evaluating the incidence of spermatic aneuploidies in
      forty males with severe oligoasthenoteratozoospermia (OAT) and comparing it with
      that in another forty males having normal semen parameters. Semen samples were
      collected and analysed in the Clinical Pathology Department according to criteria
      of the World Health Organization (WHO laboratory manual for the examination and
      processing of human semen, 2010, WHO Press). Fluorescence in situ hybridisation
      (FISH) was performed on decondensed spermatozoa from fresh semen ejaculates,
      using dual coloured chromosome-specific DNA probes labelled with fluorochromes to
      study sperm aneuploidies in chromosomes 13, 21, X and Y. There was no statistical
      significant difference between cases and controls regarding disomy frequencies
      for chromosomes 13, 21 or both combined. However, 13, 21 diploidy frequency was
      significantly higher among OAT cases. Regarding chromosomes X and Y, both cases
      and controls showed similar results for disomy/diploidy frequency for both
      chromosomes; however, there was a statistical significant increase in YY
      disomy/diploidy frequency among OAT patients. X chromosome-bearing spermatozoa
      were found to be significantly higher among controls. Patients with severe OAT
      have a higher total sperm aneuploidy rate, regarding chromosomes 13, 21, X and Y
      but without a statistical significant difference. 

PMID- 24571380
TI  - Dissociation of gas-phase bimetallic clusters as a probe of charge densities: the
      effective charge of uranyl.
AB  - Complementary experimental and computational methods for evaluating relative
      charge densities of metal cations in gas-phase clusters are presented. Collision
      induced dissociation (CID) and/or density functional theory computations were
      performed on anion clusters of composition MM'A(m+n+1)(-), where the two metal
      ions have formal charge states M(m+) and M'(n+) and A is an anion, NO3(-), Cl(-),
      or F(-) in this work. Results for alkaline earth and lanthanide metal ions reveal
      that cluster CID generally preferentially produces MA(m+1)(-) and neutral M'An if
      the surface charge density of M is greater than that of M': the metal ion with
      the higher charge density takes the extra anion. Computed dissociation energies
      corroborate that dissociation occurs via the lowest energy process. CID of
      clusters in which one of the two metal ions is uranyl, UO2(2+), shows that the
      effective charge density of U in uranyl is greater than that of alkaline earths
      and comparable to that of the late trivalent lanthanides; this is in accord with
      previous solution results for uranyl, from which an effective charge of 3.2+ was
      derived. 

PMID- 24571381
TI  - Single institution retrospective review of perioperative chemotherapy in adult
      and adolescent patients with operable osteosarcoma.
AB  - AIMS: Perioperative chemotherapy has improved the prognosis for patients with
      operable osteosarcoma. The literature is conflicting about which regimen is
      optimal. The aim of this study was to evaluate the survival outcomes of two
      cohorts of patients with operable osteosarcoma treated with different
      perioperative chemotherapy regimens. METHODS: This was a retrospective review of
      patients diagnosed with operable osteosarcoma treated at the Princess Alexandra
      Hospital from 1986 to 2009. The standard perioperative chemotherapy regimen
      changed from the modified T10 Rosen protocol to cisplatin/doxorubicin in 1997.
      Using the Kaplan-Meier method, overall survival (OS) and disease-free survival
      (DFS) curves were generated for the cisplatin/doxorubicin and the modified T10
      Rosen cohorts. RESULTS: Seventy-one patients were identified of whom 63 had
      potentially curable disease. Of these, 24 received the modified T10 Rosen regimen
      and 39 received cisplatin/doxorubicin. There was a non-significant trend toward
      better OS and DFS in the patients who received the modified T10 Rosen protocol.
      CONCLUSION: The trend toward poorer survival in the cisplatin/doxorubicin cohort,
      in combination with current evidence, has prompted our institution to change its
      practice.

PMID- 24571382
TI  - The role of homocysteine-lowering B-vitamins in the primary prevention of
      cardiovascular disease.
AB  - Cardiovascular disease (CVD) is the leading cause of mortality in the Western
      world. The effort of research should aim at the primary prevention of CVD.
      Alongside statin therapy, which is maintained to be an effective method of CVD
      prevention, there are alternative methods such as vitamin B substitution therapy
      with folic acid (FA), and vitamins B12 and B6 . B-vitamins may inhibit
      atherogenesis by decreasing the plasma level of homocysteine (Hcy)-a suspected
      etiological factor for atherosclerosis-and by other mechanisms, primarily through
      their antioxidant properties. Although Hcy-lowering vitamin trials have failed to
      demonstrate beneficial effects of B-vitamins in the prevention of CVD, a meta
      analysis and stratification of a number of large vitamin trials have suggested
      their effectiveness in cardiovascular prevention (CVP) in some aspects.
      Furthermore, interpretation of the results from these large vitamin trials has
      been troubled by statin/aspirin therapy, which was applied along with the vitamin
      substitution, and FA fortification, both of which obscured the separate effects
      of vitamins in CVP. Recent research results have accentuated a new approach to
      vitamin therapy for CVP. Studies undertaken with the aim of primary prevention
      have shown that vitamin B substitution may be effective in the primary prevention
      of CVD and may also be an option in the secondary prevention of disease if statin
      therapy is accompanied by serious adverse effects. Further investigations are
      needed to determine the validity of vitamin substitution therapy before its
      introduction in the protocol of CVD prevention. 

PMID- 24571383
TI  - Clinical applications of bovine colostrum therapy: a systematic review.
AB  - Bovine colostrum, the first milk that cows produce after parturition, contains
      high levels of growth factors and immunomodulatory components. Some healthy and
      diseased individuals may gain health benefits by consuming bovine colostrum as a
      food supplement. This review provides a systematic, critical evaluation of the
      current state of knowledge in this area. Fifty-one eligible studies were
      identified from the following databases: Medline, Embase, Global Health, the
      Cochrane Library, and the Cumulative Index to Nursing and Allied Health
      Literature. Studies were heterogeneous with regard to populations, outcomes, and
      methodological quality, as judged by the Jadad assessment tool. Many studies used
      surrogate markers to study the effects of bovine colostrum. Studies suggesting
      clinical benefits of colostrum supplementation were generally of poor
      methodological quality, and results could not be confirmed by other
      investigators. Bovine colostrum may provide gastrointestinal and immunological
      benefits, but further studies are required before recommendations can be made for
      clinical application. Animal models may help researchers to better understand the
      mechanisms of bovine colostrum supplementation, the dosage regimens required to
      obtain clinical benefits, and the optimal methods for testing these effects in
      humans. 

PMID- 24571385
TI  - A study of fatality risk and head dynamic response of cyclist and pedestrian
      based on passenger car accident data analysis and simulations.
AB  - OBJECTIVE: The current study aims to compare the fatality risk of pedestrians and
      cyclists in urban traffic through an analysis of real-world accident data in
      China. METHODS: First, 438 cases, including 371 pedestrian cases and 67 cyclist
      cases, were selected as a sample from the accidents collected through an in-depth
      investigation of vehicle accidents in China. A statistical measurement of the
      fatality risk with respect to impact velocity was carried out using a logistic
      regression analysis. Furthermore, 21 pedestrian and 24 cyclist accidents were
      selected for reconstruction with the MADYMO program. A comparative analysis was
      conducted based on the results from accident analysis and simulations for the
      fatality risk and head dynamic response of pedestrians and cyclists. RESULTS: The
      results indicate that the vehicle impact velocity has a significant relationship
      with the fatality risk of both pedestrians and cyclists. The fatality risks at 50
      km/h are more than twice as high as the risk at 40 km/h and about 5 times as high
      as that at 30 km/h for both pedestrians and cyclists. Moreover, cyclists suffered
      slightly lower fatality risk compared to pedestrians. The corresponding vehicle
      impact velocity is 65.4 km/h for pedestrian with a fatality risk of 50 percent,
      whereas for cyclists it is 67.6 km/h. In addition, the head impact conditions
      between pedestrians and cyclists are different. CONCLUSIONS: These findings offer
      potential contributions for establishing a more reasonable speed limit for urban
      traffic in China and generating strategies for cyclists' and pedestrians' head
      protection.

PMID- 24571386
TI  - Comprehensive physical model of dynamic resistive switching in an oxide
      memristor.
AB  - Memristors have been proposed for a number of applications from nonvolatile
      memory to neuromorphic systems. Unlike conventional devices based solely on
      electron transport, memristors operate on the principle of resistive switching
      (RS) based on redistribution of ions. To date, a number of experimental and
      modeling studies have been reported to probe the RS mechanism; however, a
      complete physical picture that can quantitatively describe the dynamic RS
      behavior is still missing. Here, we present a quantitative and accurate dynamic
      switching model that not only fully accounts for the rich RS behaviors in
      memristors in a unified framework but also provides critical insight for
      continued device design, optimization, and applications. The proposed model
      reveals the roles of electric field, temperature, oxygen vacancy concentration
      gradient, and different material and device parameters on RS and allows accurate
      predictions of diverse set/reset, analog switching, and complementary RS
      behaviors using only material-dependent device parameters. 

PMID- 24571384
TI  - Medical emergency team activation: performance of conventional dichotomised
      criteria versus national early warning score.
AB  - BACKGROUND: To activate the hospital's medical emergency team (MET), either
      conventional dichotomised activation criteria or an early warning scoring system
      may be used. The relative performance of these different activation patterns to
      discriminate high risk patients in a heterogenic general ward population after
      adjustment for multiple confounding factors has not been evaluated. We aimed to
      evaluate the dichotomised activation criteria used at our institution and the
      recently published national early warning score (NEWS, United Kingdom). MATERIALS
      AND METHODS: Prospective point prevalence study at a university hospital in
      Finland. On two separate days, the vital signs of all adult patients without
      treatment limitations were measured. Data on cumulative comorbidity (Charlson
      comorbidity index), age, gender, admission characteristics and subsequent
      mortality were collected. Univariate and multivariate logistic regression models
      were used for unadjusted and adjusted performance testing. RESULTS: The cohort
      consisted of 615 patients. The dichotomised activation criteria were not
      associated with in-hospital serious adverse events (odds ratio 1.87, 95%
      confidence interval 0.55-6.30) or 30-day mortality (2.13, 0.79-5.72) after
      adjustments. For a NEWS of seven or more (the suggested trigger level for
      immediate MET activation), the adjusted odds ratios for the above mentioned
      outcomes were 7.45 (2.39-23.3) and 11.4 (4.40-29.6), respectively. Unlike the
      dichotomised activation criteria, NEWS was also independently associated with a
      higher 60- and 180-day mortality after adjustments. CONCLUSIONS: NEWS
      discriminates high risk patients in a heterogenic general ward population
      independently of multiple confounding factors. The conventional dichotomised
      activation criteria were not able to detect high risk patients.

PMID- 24571387
TI  - Creating a vision for the future: key competencies and strategies for culturally
      competent practice with lesbian, gay, bisexual, and transgender (LGBT) older
      adults in the health and human services.
AB  - Sexual orientation and gender identity are not commonly addressed in health and
      human service delivery, or in educational degree programs. Based on findings from
      Caring and Aging with Pride: The National Health, Aging and Sexuality Study
      (CAP), the first national federally-funded research project on LGBT health and
      aging, this article outlines 10 core competencies and aligns them with specific
      strategies to improve professional practice and service development to promote
      the well-being of LGBT older adults and their families. The articulation of key
      competencies is needed to provide a blueprint for action for addressing the
      growing needs of LGBT older adults, their families, and their communities. 

PMID- 24571388
TI  - Forecast of natural aquifer discharge using a data-driven, statistical approach.
AB  - In the Western United States, demand for water is often out of balance with
      limited water supplies. This has led to extensive water rights conflict and
      litigation. A tool that can reliably forecast natural aquifer discharge months
      ahead of peak water demand could help water practitioners and managers by
      providing advanced knowledge of potential water-right mitigation requirements.
      The timing and magnitude of natural aquifer discharge from the Eastern Snake
      Plain Aquifer (ESPA) in southern Idaho is accurately forecast 4 months ahead of
      the peak water demand, which occurs annually in July. An ARIMA time-series model
      with exogenous predictors (ARIMAX model) was used to develop the forecast. The
      ARIMAX model fit to a set of training data was assessed using Akaike's
      information criterion to select the optimal model that forecasts aquifer
      discharge, given the previous year's discharge and values of the predictor
      variables. Model performance was assessed by application of the model to a
      validation subset of data. The Nash-Sutcliffe efficiency for model predictions
      made on the validation set was 0.57. The predictor variables used in our forecast
      represent the major recharge and discharge components of the ESPA water budget,
      including variables that reflect overall water supply and important aspects of
      water administration and management. Coefficients of variation on the regression
      coefficients for streamflow and irrigation diversions were all much less than
      0.5, indicating that these variables are strong predictors. The model with the
      highest AIC weight included streamflow, two irrigation diversion variables, and
      storage. 

PMID- 24571390
TI  - A highly selective chemosensor for Al(III) and Zn(II) and its coordination with
      metal ions.
AB  - This paper reports a fluorescence chemosensor, N-(benzimidazol-2
      yl)salicylaldimine (H2L), for Zn(II) and Al(III) ions. H2L has high selectivity
      for Al(III) in dimethyl sulfoxide (DMSO) and for Zn(II) in N,N-dimethylformamide
      (DMF). In methanol, Zn(II) and Al(III) could also be distinguished by H2L with
      different excitation wavelengths. The fluorescent species
      [Zn(HL)(H2O)(CH3OH)](+), [Zn(HL)(H2O)(DMF)](+), [Al(HL)2(OH)(H2O)], and
      [Al(HL)(OH)2(H2O)(DMSO)] formed in solution were established by a combination of
      experimental and theoretical methods, including Job's plot, (1)H NMR titration,
      electrospray inonization mass spectrometry (ESI-MS), and B3LYP-SCRF/6-31(d) and
      TD-B3LYP-SCRF/6-31G* density functional theory methods. The results show that
      Zn(II) and Al(III) are all coordinated to the imine nitrogen atom and the
      hydroxyl oxygen atom from H2L, which is the same as the M(2+) ions in the
      obtained mononuclear complexes [M(HL)2(CH3OH)2] (where M = Cd, Ni, Co, and Mg).
      The detection limits of H2L for Zn(II) were 5.98 MUM in methanol and 5.76 MUM in
      DMF, while the detection limits of H2L for Al(III) were 3.3 MUM in methanol and
      5.25 MUM in DMSO. Furthermore, it is also confirmed that H2L has low toxicity for
      HeLa cells and could be used to detect Zn(II) and Al(III) ions in living cells by
      bioimaging. 

PMID- 24571389
TI  - Glycoprotein biomarker panel for pancreatic cancer discovered by quantitative
      proteomics analysis.
AB  - Pancreatic cancer is a lethal disease where specific early detection biomarkers
      would be very valuable to improve outcomes in patients. Many previous studies
      have compared biosamples from pancreatic cancer patients with healthy controls to
      find potential biomarkers. However, a range of related disease conditions can
      influence the performance of these putative biomarkers, including pancreatitis
      and diabetes. In this study, quantitative proteomics methods were applied to
      discover potential serum glycoprotein biomarkers that distinguish pancreatic
      cancer from other pancreas related conditions (diabetes, cyst, chronic
      pancreatitis, obstructive jaundice) and healthy controls. Aleuria aurantia lectin
      (AAL) was used to extract fucosylated glycoproteins and then both TMT protein
      level labeling and label-free quantitative analysis were performed to analyze
      glycoprotein differences from 179 serum samples across the six different
      conditions. A total of 243 and 354 serum proteins were identified and quantified
      by label-free and TMT protein-level quantitative strategies, respectively.
      Nineteen and 25 proteins were found to show significant differences in samples
      between the pancreatic cancer and other conditions using the label-free and TMT
      strategies, respectively, with 7 proteins considered significant in both methods.
      Significantly different glycoproteins were further validated by lectin-ELISA and
      ELISA assays. Four candidates were identified as potential markers with profiles
      found to be highly complementary with CA 19-9 (p < 0.001). Obstructive jaundice
      (OJ) was found to have a significant impact on the performance of every marker
      protein, including CA 19-9. The combination of alpha-1-antichymotrypsin (AACT),
      thrombospondin-1 (THBS1), and haptoglobin (HPT) outperformed CA 19-9 in
      distinguishing pancreatic cancer from normal controls (AUC = 0.95), diabetes (AUC
      = 0.89), cyst (AUC = 0.82), and chronic pancreatitis (AUC = 0.90). A marker panel
      of AACT, THBS1, HPT, and CA 19-9 showed a high diagnostic potential in
      distinguishing pancreatic cancer from other conditions with OJ (AUC = 0.92) or
      without OJ (AUC = 0.95). 

PMID- 24571391
TI  - Knowledge, attitudes, and practices towards prevention and early detection of
      chronic kidney disease.
AB  - OBJECTIVE: To describe the knowledge, attitudes and practices of Jordanian
      patients with chronic illnesses towards prevention and early detection of chronic
      kidney disease. BACKGROUND: Patients with chronic illnesses such as hypertension
      and diabetes need to adopt healthy attitudes and practices and gain knowledge
      regarding prevention and early detection of kidney disease to decrease the
      prevalence of dialysis-related complications and costs. METHODS: A total of 740
      patients were recruited from out-patients clinics in Jordan. Knowledge, attitudes
      and practices about kidney disease prevention and early detection were measured
      using the Chronic Kidney Disease Screening Index which was developed by the
      researcher and tested for validity and reliability. RESULTS: The results revealed
      that most of the participants have knowledge about kidney disease; however, half
      of them had wrong information related to signs and symptoms of chronic kidney
      disease. The majority of the participants were not aware about the importance of
      discovering health problems at early stages. CONCLUSION AND IMPLICATIONS:
      Improvement in population understanding about chronic kidney disease is needed to
      advance their awareness and practices to make appropriate decisions towards
      health promotion and better quality of life. IMPLICATION FOR POLICY DEVELOPMENT:
      Nurses need to be involved in development of protocols for screening and
      intervention programmes, taking into consideration the cultural issues and the
      financial status of individuals at risk for kidney disease. Governments should
      adopt a public health policy for chronic kidney disease that supports programmes
      for screening and programmes for improving public awareness for kidney disease
      prevention.

PMID- 24571393
TI  - Diffusible signal factor-repressed extracellular traits enable attachment of
      Xylella fastidiosa to insect vectors and transmission.
AB  - The hypothesis that a wild-type strain of Xylella fastidiosa would restore the
      ability of rpfF mutants blocked in diffusible signal factor production to be
      transmitted to new grape plants by the sharpshooter vector Graphocephala
      atropunctata was tested. While the rpfF mutant was very poorly transmitted by
      vectors irrespective of whether they had also fed on plants infected with the
      wild-type strain, wild-type strains were not efficiently transmitted if vectors
      had fed on plants infected with the rpfF mutant. About 100-fewer cells of a wild
      type strain attached to wings of a vector when suspended in xylem sap from plants
      infected with an rpfF mutant than in sap from uninfected grapes. The frequency of
      transmission of cells suspended in sap from plants that were infected by the rpfF
      mutant was also reduced over threefold. Wild-type cells suspended in a culture
      supernatant of an rpfF mutant also exhibited 10-fold less adherence to wings than
      when suspended in uninoculated culture media. A factor released into the xylem by
      rpfF mutants, and to a lesser extent by the wild-type strain, thus inhibits their
      attachment to, and thus transmission by, sharpshooter vectors and may also enable
      them to move more readily through host plants.

PMID- 24571394
TI  - Genetic variation and possible mechanisms driving the evolution of worldwide fig
      mosaic virus isolates.
AB  - Fig mosaic virus (FMV) is a multipartite negative-sense RNA virus infecting fig
      trees worldwide. FMV is transmitted by vegetative propagation and grafting of
      plant materials, and by the eriophyid mite Aceria ficus. In this work, the
      genetic variation and evolutionary mechanisms shaping FMV populations were
      characterized. Nucleotide sequences from four genomic regions (each within the
      genomic RNAs 1, 2, 3, and 4) from FMV isolates from different countries were
      determined and analyzed. FMV genetic variation was low, as is seen for many other
      plant viruses. Phylogenetic analysis showed some geographically distant FMV
      isolates which clustered together, suggesting long-distance migration. The extent
      of migration was limited, although varied, between countries, such that FMV
      populations of different countries were genetically differentiated. Analysis
      using several recombination algorithms suggests that genomes of some FMV isolates
      originated by reassortment of genomic RNAs from different genetically similar
      isolates. Comparison between nonsynonymous and synonymous substitutions showed
      selection acting on some amino acids; however, most evolved neutrally. This and
      neutrality tests together with the limited gene flow suggest that genetic drift
      plays an important role in shaping FMV populations.

PMID- 24571395
TI  - Chest physiotherapy is not clinically indicated for infants receiving outpatient
      care for acute wheezing episodes.
AB  - AIM: To evaluate the effectiveness of chest physiotherapy (CPT), which provides
      slow and long expiratory flow and assisted cough techniques, in infants receiving
      outpatient care for acute wheezing episodes. METHODS: Forty-eight infants with
      moderate acute wheezing episodes were randomised to receive either salbutamol MDI
      with CPT (n = 25) or without CPT (n = 23). The clinical score and SpO2 levels
      were recorded, before and after treatment, in a blinded design. The primary
      outcome was discharge after the first hour of treatment: clinical score <=5/12
      and SpO2 >= 93%. Secondary outcomes were the number of admissions to hospital
      after the second hour, use of oral corticosteroid bursts and admissions to
      hospital on day seven. RESULTS: There were no differences between children with
      and without CPT in discharge rate (92% vs. 87%), clinical score (median [IQR]:
      2.8 [2.2-3.3] vs. 3.4 [2.8-4.1]) and SpO2 = (96.4 [95.7-97.1] vs. 96.0 [94.9
      96.5]) after the first hour of treatment or in the number of hospital admissions
      after the second hour. No differences were observed at days seven and 28
      following treatment. CONCLUSION: There was no evidence of clinical benefits from
      these specific CPT techniques for infants receiving outpatient care for acute
      wheezing episodes.

PMID- 24571396
TI  - Likelihood-based analysis of longitudinal data from outcome-related sampling
      designs.
AB  - Investigators commonly gather longitudinal data to assess changes in responses
      over time and to relate these changes to within-subject changes in predictors.
      With rare or expensive outcomes such as uncommon diseases and costly radiologic
      measurements, outcome-dependent, and more generally outcome-related, sampling
      plans can improve estimation efficiency and reduce cost. Longitudinal follow up
      of subjects gathered in an initial outcome-related sample can then be used to
      study the trajectories of responses over time and to assess the association of
      changes in predictors within subjects with change in response. In this article,
      we develop two likelihood-based approaches for fitting generalized linear mixed
      models (GLMMs) to longitudinal data from a wide variety of outcome-related
      sampling designs. The first is an extension of the semi-parametric maximum
      likelihood approach developed in Neuhaus, Scott and Wild (2002, Biometrika 89, 23
      37) and Neuhaus, Scott and Wild (2006, Biometrics 62, 488-494) and applies quite
      generally. The second approach is an adaptation of standard conditional
      likelihood methods and is limited to random intercept models with a canonical
      link. Data from a study of attention deficit hyperactivity disorder in children
      motivates the work and illustrates the findings. 

PMID- 24571397
TI  - Factors affecting ranging behaviour in young and adult laying hens.
AB  - 1. A study was conducted to investigate the effect of environment on ranging in
      33 flocks reared with (16) or without (17) range access. Ranging was observed at
      8, 16 and 35 weeks. Information on house layout, weather conditions and range
      characteristics was used to create models predicting the percentage of the flock
      out on the range and the percentage of ranging birds observed away from the
      house. 2. Three flocks had range access at 8 weeks. The percentage of birds
      ranging averaged 28%, with 22% of these ranging away from the house. For the 13
      flocks with range access at 16 weeks, the percentage of pullets on the range was
      12%, with 29% of these ranging away from the house. At 35 weeks, all flocks had
      range access and the average percentage of birds out on the range was 13%, with
      42% of these ranging away from the house. 3. The percentage of birds seen using
      the range was higher with reduced flock size and stocking density, increased pop
      hole availability (cm/bird) and light intensity inside the house. More birds
      ranged on cooler days and on farms located in areas with fewer days of rain per
      year and lower average rainfall. The percentage of birds ranging varied with
      season and was lowest in May. More birds ranged away from the house when cover
      and more artificial structures were present on the range. The proportion of
      ranging birds located away from the house increased with lower outdoor humidity
      levels, higher air pressure, and on warmer days. Lastly, birds ranged away from
      the house more as they got older.

PMID- 24571398
TI  - The political downside of dual identity: group identifications and religious
      political mobilization of Muslim minorities.
AB  - Research on the political mobilization of ethnic minorities has shown that dual
      ethno-national identification facilitates involvement in political action on
      behalf of the ethnic group. This study extends this research by proposing that a
      dual identity can impede political mobilization on behalf of another relevant in
      group--the religious community - especially if this in-group is not accepted by
      the wider society. Using a sample of 641 Muslims of Turkish origin living in
      Germany and the Netherlands, dual ethno-national identity (Turkish-German/Turkish
      Dutch) was examined in relation to religious Muslim identification and religious
      political mobilization. Dual identity was expected to be indirectly related to
      lower mobilization via decreased religious group identification. Further, this
      mediating process was predicted to be stronger for Turkish Muslims who perceived
      relatively high religious group discrimination. In both countries we found
      support for the mediating hypothesis, however, the moderating role of
      discrimination was confirmed only for the Netherlands. Turkish-Dutch
      identification was associated with lower support for religious political
      mobilization because of lower Muslim identification only for Turkish-Dutch
      participants who perceived high levels of discrimination. These findings indicate
      that a strong dual (ethno-national) identity can undermine minority members'
      support for political rights and actions on behalf of a third relevant in-group,
      and therefore qualify the social psychological benefits of the dual identity
      model.

PMID- 24571400
TI  - Paresthesia mapping: a practical workup for successful implantation of the dorsal
      root ganglion stimulator in refractory groin pain.

PMID- 24571399
TI  - Outcome of acute East African trypanosomiasis in a Polish traveller treated with
      pentamidine.
AB  - BACKGROUND: African trypanosomiasis is a parasitic infection sporadically
      imported to Europe by tourists or immigrants returning from endemic areas. We
      present the first and an unusual case of East African trypanosomiasis imported to
      Poland by a patient returning from a tourist trip to Uganda and Rwanda, which was
      successfully treated with pentamidine. CASE PRESENTATION: A 61-year-old Polish
      man was admitted to the Department because of high-grade fever and multi-organ
      dysfunction after a tourist trip to East Africa. He experienced a single tsetse
      fly bite during a safari trip to the Queen Elizabeth National Park in Uganda. On
      admission, his clinical status was severe, with high fever of 41oC, preceded by
      chills, bleeding from the gums and oral mucosa, haemorrhages at the sites of
      venipuncture, numerous ecchymoses, fine-spotted skin rash, tachycardia,
      hepatosplenomegaly, dehydration, jaundice, dyspnoea, hypoxaemia, generalised
      oedema and oliguria. There was a typical non-painful trypanosomal chancre with
      central necrosis and peripheral erythema on his left arm. Laboratory
      investigations showed leucopenia, thrombocytopenia, haemolytic anaemia,
      hyperbilirubinaemia, hypoglycaemia, elevated creatinine and urea, high activity
      of aminotransferases, elevated levels of inflammatory markers, hypoproteinaemia,
      proteinuria, abnormal clotting and bleeding times, low fibrinogen level,
      metabolic acidosis, and electrolyte disturbances. A peripheral blood smear showed
      numerous Trypanosoma brucei trypomastigotes with a massive parasitaemia of
      100,000/MUl. T. brucei rhodesiense subspecies was finally identified on the basis
      of the characteristic serum resistance-associated gene using a polymerase chain
      reaction, and a seroconversion of specific immunoglobulin M and G antibodies in
      the peripheral blood by enzyme-linked immunosorbent assay. Serological tests for
      T. brucei gambiense subspecies were negative. A severe clinical course of acute
      rhodesiense trypanosomiasis with renal failure, respiratory distress,
      disseminated intravascular coagulation syndrome, haemolysis, liver insufficiency
      and myocarditis was confirmed. Intensive anti-parasitic and symptomatic treatment
      was immediately instituted, including intravenous pentamidine, plasmaphereses,
      oxygen therapy, blood transfusion, catecholamine administration, and fluid
      infusions, as well as haemostatic, hepatoprotective, anti-inflammatory,
      antipyretic and diuretic drugs. The final outcome was a full recovery with no
      late sequelae. CONCLUSION: Sleeping sickness should always be considered in the
      differential diagnosis of fever in people returning from safari trips to the
      national parks or nature reserves of sub-Saharan Africa.

PMID- 24571401
TI  - In-reach nursing services improve older patient outcomes and access to emergency
      care.
AB  - AIMS: To identify the impact of in-reach services providing specialist nursing
      care on outcomes for older people presenting to the emergency department from
      residential aged care. METHODS: Retrospective cohort study compared clinical
      outcomes of 2278 presentations from 2009 with 2051 presentations from 2011 before
      and after the implementation of in-reach services. RESULTS: Median emergency
      department length of stay decreased by 24 minutes (7.0 vs 6.6 hours, P < 0.001)
      and admission rates decreased by 23% (68 vs 45%, P < 0.001). The proportion of
      people with repeat emergency department visits within six months decreased by 12%
      (27 vs 15%). The proportion of admitted patients who were discharged with an end
      of life palliative care plan increased by 13% (8 vs 21%, P = 0.007). CONCLUSIONS:
      There was a significant reduction in the median length of stay, fewer hospital
      admissions and fewer repeat visits for people from residential aged care
      following implementation of in-reach services.

PMID- 24571403
TI  - Fracture resistance of endodontically restored, weakened incisors.
AB  - OBJECTIVES: To test the fracture strength of weakened bovine incisors
      endodontically treated with mineral trioxide aggregate (MTA), calcium phosphate
      bone cement (CPBC) or fibre reinforced composite (FRC) posts, and to evaluate the
      fracture mode. METHODS: Weakened bovine incisors (n = 75), standardized according
      to the dentinal wall thickness at the cervical area, were randomly assigned to
      one control group and three experimental groups. Unfilled teeth were assigned to
      group 1 (n = 20) and served as control group. Group 2 (n = 17) consisted of teeth
      filled with MTA. In group 3 (n = 18), the incisors were filled with CPBC and in
      group 4 (n = 20) with FRC posts. All specimens were subjected to load at a cross
      head speed of 60 mm min(-1) until fracture occurred. The initial (IL) and final
      fracture (FL) loads (N) were recorded, and the failure mode among the different
      groups was evaluated. RESULTS: anova showed a statistically significant
      difference in fracture load among the groups. Tukey's test revealed a significant
      difference for the IL between the control group and the experimental groups with
      exception of the MTA group. The FL was not significantly different among the
      experimental groups. A high percentage of favourable fractures was seen in the
      FRC and CPBC groups. CONCLUSION: FRC posts and CPBC could be promising materials
      to strengthen non-vital structurally compromised teeth.

PMID- 24571402
TI  - The current state of adhesive dentistry: a guide for clinical practice.
AB  - Adhesive dentistry is key to minimally invasive, esthetic, and tooth-preserving
      dental restorations. These are typically realized by bonding various restorative
      materials, such as composite resins, ceramics, or even metal alloys, to tooth
      structures or other materials with composite resin luting agents. For optimal
      bond strengths and long-lasting clinical success, however, these material and
      tooth substrates require their respective pretreatment steps, based on their
      natures and compositions. Today, dental adhesion is used in almost all dental
      specialties. This article summarizes key aspects and guidelines for clinical
      success with adhesive dentistry and summarizes information presented at the 5th
      International Congress on Adhesive Dentistry. 

PMID- 24571404
TI  - Complete F-type mitochondrial genome of Chinese freshwater mussels Lamprotula
      gottschei.
AB  - Lamprotula gottschei (Von Martens, 1894) is one of the freshwater pearl mussels
      which have great meaning on economy in China. The complete F-type mitochondrial
      genome of L. gottschei was firstly determined. This circle genome (15,915 bp in
      size) comprises 13 protein-coding genes, 22 tRNA genes, 2 rRNA genes, except for
      COI, CYTB, ND4, ND6 and ND4L, with ATA start codon, the remaining protein-coding
      genes initiated with the orthodox ATG start codon. There were 25 non-coding
      regions found throughout the mitogenome of L. gottschei, ranging in size from 1
      to 305 bp, the largest of which is between ND2 and tRNA(Gln) (305 bp), and is
      longer than the control region sequences (about 280 bp) of freshwater mussels
      from Poland and South Korea. Strictly maternal inheritance (SMI) of mitochondrial
      DNA (mtDNA) is the standard rule in nearly all anisogamic organisms (SMI), (Roze
      et al., 2005; White et al., 2008). However, bivalves of the marine family
      Mytilidae and Veneroida as well as the freshwater family Unionidae possess two
      independently inheritance mode of mitochondrial DNA (mtDNA) (Boyle & Etter,
      2013), which involves maternal (F) and paternal (M) transmission routes
      concomitant with highly divergent gender-associated mtDNA genomes. This system of
      mtDNA transmission was called doubly uniparental inheritance (DUI) (Zouros,
      2000).

PMID- 24571405
TI  - The complete chloroplast genome sequence of sugar beet (Beta vulgaris ssp.
      vulgaris).
AB  - The complete nucleotide sequence of the sugar beet (Beta vulgaris ssp. vulgaris)
      chloroplast genome (cpDNA) was determined in this study. The cpDNA was 149,637 bp
      in length, containing a pair of 24,439 bp inverted repeat regions (IR), which
      were separated by small and large single copy regions (SSC and LSC) of 17,701 and
      83,057 bp, respectively. 53.4% of the sugar beet cpDNA consisted of gene coding
      regions (protein coding and RNA genes). The gene content and relative positions
      of 113 individual genes (79 protein encoding genes, 30 tRNA genes, 4 rRNA genes)
      were almost identical to those of tobacco cpDNA. The overall AT contents of the
      sugar beet cpDNA were 63.6% and in the LSC, SSC and IR regions were 65.9%, 70.8%
      and 57.8%, respectively. Fifteen genes contained one intron, while three genes
      had two introns.

PMID- 24571406
TI  - Phylogenetic analysis of the Black Stork Ciconia nigra (Ciconiiformes:
      Ciconiidae) based on complete mitochondrial genome.
AB  - The Black Stork, Ciconia nigra belongs to family Ciconiidae, which is evaluated
      as Least Concern by IUCN. In this study, the complete mitochondrial genome of C.
      nigra was first sequenced and characterized, which was 17,795 bp in length. The
      mt-genome has tandem repeats of 80 bp and 78 bp repeat units, and AAACAAC and
      AAACAAACAAC tandem repeats in D-loop region. It is notable that a single extra
      base "C" at position 174 was inserted in gene ND3. Bayesian inference, maximum
      likelihood methods were used to construct phylogenetic trees based on 12 heavy
      strand protein-coding genes. Phylogenetic analyses showed that Ardeidae diverged
      earlier than Ciconiidae, Cathartida and Threskiornithidae, and Ciconiidae had
      closest relationship to Cathartida. C. nigra diverged first among three Ciconia
      birds.

PMID- 24571407
TI  - "They just don't have a clue": transgender aging and implications for social
      work.
AB  - This article explores transgender aging, drawing from life story interviews with
      transgender adults aged 62-78. The analysis focuses on 3 themes: intersections of
      age and gender during the life course, lack of knowledge of transgender issues,
      and how previous experiences of accessing care and social services matter in
      later life. It illustrates how older transgendered adults carry physical and
      mental scars from previously encountered transphobia, which affect various
      aspects of later life. Implications for social work are discussed and client
      centered care, with a biographical approach, is suggested to better meet the
      needs of transgendered older adults. 

PMID- 24571409
TI  - Multi-functionality of macroporous TiO2 spheres in dye-sensitized and hybrid
      heterojunction solar cells.
AB  - Micron-sized macroporous TiO2 spheres (MAC-TiO2) were synthesized using a
      colloidal templating process inside emulsions, which were then coated on a
      nanocrystalline TiO2 light absorption film to prepare a bilayered photoanode for
      liquid-based dye-sensitized solar cells (DSSC) and hybrid heterojunction solid
      state solar cells. MAC-TiO2 layers can enhance light scattering as well as
      absorption, because their pore size and periodicity are comparable to light
      wavelength for unique multiple scattering and a porous surface can load dye more.
      Moreover, due to the bicontinuous nature of macropores and TiO2 walls,
      electrolyte could be transported much faster in between the TiO2 spheres rather
      than within the small TiO2 nonporous architectures. Electron transport was also
      facilitated along the interconnected TiO2 walls. In DSSCs with these MAC-TiO2
      scattering layers, efficiency was higher than conventional DSSCs incorporating a
      commercial scattering layer. The unique geometry of MAC-TiO2 results in strong
      improvements in light scattering and infiltration of hole-transporting materials,
      thereby the MAC-TiO2-based solid-state device showed comparatively higher
      efficiency than the device with conventional nanocrystalline TiO2. 

PMID- 24571410
TI  - NH4FeCl2(HCOO): synthesis, structure, and magnetism of a novel low-dimensional
      magnetic material.
AB  - Solvothermal synthesis was used to create a low-dimensional iron(II) chloride
      formate compound, NH4FeCl2(HCOO), that exhibits interesting magnetic properties.
      NH4FeCl2(HCOO) crystallizes in the monoclinic space group C2/c (No. 15) with a =
      7.888(1) A, b = 11.156(2) A, c = 6.920(2) A, and beta = 108.066(2) degrees . The
      crystal structure consists of infinite zigzag chains of distorted Fe(2+)-centered
      octahedra linked by MU2-Cl and syn-syn formate bridges, with interchain hydrogen
      bonding through NH4(+) cations holding the chains together. The unique Fe(2+)
      site is coordinated by four equatorial chlorides at a distance of 2.50 A and two
      axial oxygens at a distance of 2.08 A. Magnetic measurements performed on powder
      and oriented single-crystal samples show complex anisotropic magnetic behavior
      dominated by antiferromagnetic interactions (TN = 6 K) with a small ferromagnetic
      component in the direction of chain propagation. An anisotropic metamagnetic
      transition was observed in the ordered state at 2 K in an applied magnetic field
      of 0.85-3 T. (57)Fe Mossbauer spectroscopy reveals mixed hyperfine interactions
      below the ordering temperature, with strong electric field gradients and complex
      noncollinear arrangement of the magnetic moments. 

PMID- 24571411
TI  - The influence of bicycle oriented facilities on bicycle crashes within crash
      concentrated areas.
AB  - OBJECTIVE: This study analyzes environmental features that influence bicycle
      crashes within crash concentrated areas. This study particularly provides a
      systemic approach to analyzing major bicycle oriented facilities contributing to
      bicycle crashes within crash concentrated areas. METHODS: This study applies
      geographic information systems (GIS) to the identification of crash concentrated
      areas in Riverside County, California using five years of crash data as well as
      the development of environment feature data inventory. Based on the data
      inventory, a regression method was applied to discover whether there was a
      correlation between the presence of bicycle facilities and the occurrence of
      bicycle crashes. RESULTS: This study identifies that longer distance between
      crosswalks and bus stops are positively associated with bicyclist crashes, while
      structured medians contribute to the reduction of bicycle crashes. This study
      also suggests that parking lot entrance ways and parking lots with no physical
      barrier from sidewalks cause bicycle crashes on sidewalks. CONCLUSIONS: This
      study presents guidelines for local transportation planners to analyze the
      patterns of bicyclist crashes in order to improve roadway safety. This research
      also assists planners in effectively allocating scarce resources as they address
      issues of bicyclist safety.

PMID- 24571408
TI  - Pathogenesis of percutaneous infection of goats with Burkholderia pseudomallei:
      clinical, pathologic, and immunological responses in chronic melioidosis.
AB  - Melioidosis is a severe suppurative to granulomatous infection caused by
      Burkholderia pseudomallei. The disease is endemic to South-East Asia and Northern
      Australasia and is also of interest as a potential biological weapon. Natural
      infection can occur by percutaneous inoculation, inhalation or ingestion, but the
      relative importance of each route is unknown. Experimental infection models using
      mice have shown inhalation to be the most lethal route of exposure, but few
      studies have examined the pathogenesis of percutaneous infection despite its
      presumptive importance in natural disease. Caprine models are useful in the study
      of melioidosis because goats are susceptible to natural infection by B.
      pseudomallei, display similar epizootiology/epidemiology to that of humans within
      the endemic range and develop similar pathologic lesions. Percutaneous
      inoculation with 10(4)  CFU of B. pseudomallei produced disease in all
      experimental animals with rapid dissemination to the lungs, spleen and kidneys.
      Initial fever was brief, but temperatures did not return to pre-infection levels
      until day 18, concurrent with a dramatic lymphocytosis and the transition to
      chronic disease. Distribution and appearance of gross pathologic and radiographic
      lesions in goats were similar to caprine aerosol infection and to reported human
      disease. The similarities seen despite different routes of infection suggest that
      host or bacterial factors may be more important than the route of infection in
      disease pathogenesis. The nature of melioidosis in goats makes it amenable for
      modelling additional risk factors to produce acute clinical disease, which is
      important to the study of human melioidosis. 

PMID- 24571412
TI  - Cardiac arrest teams and medical emergency teams in Finland: a nationwide cross
      sectional postal survey.
AB  - BACKGROUND: The implementation, characteristics and utilisation of cardiac arrest
      teams (CATs) and medical emergency teams (METs) in Finland are unknown. We aimed
      to evaluate how guidelines on advanced in-hospital resuscitation have been
      translated to practice. METHODS: A cross-sectional postal survey including all
      public hospitals providing anaesthetic services. RESULTS: Of the 55 hospitals, 51
      (93%) participated in the study. All hospitals with intensive care units
      (university and central hospitals, n = 24) took part. In total, 88% of these
      hospitals (21/24) and 30% (8/27) of the small hospitals had CATs. Most hospitals
      with CATs (24/29) recorded team activations. A structured debriefing after a
      resuscitation attempt was organised in only one hospital. The median incidence of
      in-hospital cardiac arrest in Finland was 1.48 (Q1 = 0.93, Q3 = 1.93) per 1000
      hospital admissions. METs had been implemented in 31% (16/51) of the hospitals. A
      physician participated in MET activation automatically in half (8/16) of the
      teams. Operating theatres (13/16), emergency departments (10/16) and paediatric
      wards (7/16) were the most common sites excluded from the METs' operational
      areas. The activation thresholds for vital signs varied between hospitals. The
      lower upper activation threshold for respiratory rate was associated with a
      higher MET activation rate. The national median MET activation rate was 2.3 (1.5,
      4.8) per 1000 hospital admissions and 1.5 (0.96, 4.0) per every cardiac arrest.
      CONCLUSIONS: Current guidelines emphasise the preventative actions on in-hospital
      cardiac arrest. Practices are changing accordingly but are still suboptimal
      especially in central and district hospitals. Unified guidelines on rapid
      response systems are required.

PMID- 24571413
TI  - Ruthenium-catalyzed oxidation of allyl alcohols with intermolecular hydrogen
      transfer: synthesis of alpha,beta-unsaturated carbonyl compounds.
AB  - Ruthenium-catalyzed oxidation of multisubstituted allyl alcohols in the presence
      of benzaldehyde gives enals or enones in good yields. Unlike the commonly
      reported ruthenium-catalyzed isomerization reaction of allyl alcohols to give
      saturated ketones, an intermolecular rather than intramolecular hydrogen transfer
      is involved in this transformation. This reaction offers an efficient, mild, and
      high-yielding method for the preparation of substituted alpha,beta-unsaturated
      compounds. 

PMID- 24571414
TI  - New frontiers for veterinary anaesthesia: the development of veterinary patient
      safety culture.

PMID- 24571415
TI  - SEAWAT-based simulation of axisymmetric heat transport.
AB  - Simulation of heat transport has its applications in geothermal exploitation of
      aquifers and the analysis of temperature dependent chemical reactions. Under
      homogeneous conditions and in the absence of a regional hydraulic gradient,
      groundwater flow and heat transport from or to a well exhibit radial symmetry,
      and governing equations are reduced by one dimension (1D) which increases
      computational efficiency importantly. Solute transport codes can simulate heat
      transport and input parameters may be modified such that the Cartesian geometry
      can handle radial flow. In this article, SEAWAT is evaluated as simulator for
      heat transport under radial flow conditions. The 1971, 1D analytical solution of
      Gelhar and Collins is used to compare axisymmetric transport with retardation
      (i.e., as a result of thermal equilibrium between fluid and solid) and a large
      diffusion (conduction). It is shown that an axisymmetric simulation compares well
      with a fully three dimensional (3D) simulation of an aquifer thermal energy
      storage systems. The influence of grid discretization, solver parameters, and
      advection solution is illustrated. Because of the high diffusion to simulate
      conduction, convergence criterion for heat transport must be set much smaller
      (10(-10) ) than for solute transport (10(-6) ). Grid discretization should be
      considered carefully, in particular the subdivision of the screen interval. On
      the other hand, different methods to calculate the pumping or injection rate
      distribution over different nodes of a multilayer well lead to small differences
      only. 

PMID- 24571416
TI  - Prevalence of macrolide resistance among group A streptococci isolated from
      pharyngotonsillitis.
AB  - A GAS Surveillance Study Group was organized to analyze group A streptococci
      (GAS) isolated from patients with acute pharyngotonsillitis, with participating
      pediatricians submitting swab samples between April and October 2012. Molecular
      analysis of emm typing and multilocus sequence typing (MLST), as well as
      antimicrobial susceptibility testing, were carried out for 363 GAS isolates.
      Strains belonging to emm1 were most prevalent (25.6%), followed in turn by emm12
      (23.7%), emm28 (16.3%), and emm89 (15.3%). In emm1, 87.2% of strains, typed as
      ST28 or ST661, showed macrolide (ML) resistance mediated by the mef(A) gene. In
      emm12 (ST36 and ST465), 64.3% of strains were resistant to MLs because of mef(A)
      or erm(B), as was also true for 81.7% of emm28 (ST52). In emm89 (ST101 and
      ST646), however, such resistance was not seen. Due to the high levels of ML
      resistance observed, GAS isolates from individuals with penicillin allergies need
      to be isolated and their antimicrobial susceptibility tested, rather than
      automatically giving the patient a ML. 

PMID- 24571417
TI  - Effect of filter designs on hydraulic properties and well efficiency.
AB  - To analyze the effect of filter pack arrangement on the hydraulic properties and
      the well efficiency of a well design, a step drawdown was conducted in a sand
      filled tank model. Prior to the test, a single filter pack (SFP), granule only,
      and two dual filter packs (DFPs), type A (granule-pebble) and type B (pebble
      granule), were designed to surround the well screen. The hydraulic properties and
      well efficiencies related to the filter packs were evaluated using the Hazen's,
      Eden-Hazel's, Jacob's, and Labadie-Helweg's methods. The results showed that the
      hydraulic properties and well efficiency of the DFPs were higher than those of a
      SFP, and the clogging effect and wellhead loss related to the aquifer material
      were the lowest owing to the grain size and the arrangement of the filter pack.
      The hydraulic conductivity of the DFPs types A and B was about 1.41 and 6.43
      times that of a SFP, respectively. In addition, the well efficiency of the DFPs
      types A and B was about 1.38 and 1.60 times that of the SFP, respectively. In
      this study, hydraulic property and well efficiency changes were observed
      according to the variety of the filter pack used. The results differed from the
      predictions of previous studies on the grain-size ratio. Proper pack-aquifer
      ratios and filter pack arrangements are primary factors in the construction of
      efficient water wells, as is the grain ratio, intrinsic permeability (k), and
      hydraulic conductivity (K) between the grains of the filter packs and the grains
      of the aquifer. 

PMID- 24571418
TI  - Development, implementation and impact of simple patient safety interventions in
      a university teaching hospital.
AB  - OBJECTIVE: To determine the incidence of anesthesia patient safety incidents at a
      university teaching hospital, develop interventions to address the most common
      incidents, and determine the effectiveness of these interventions. STUDY DESIGN:
      Pre-post intervention observational. ANIMALS: Four thousand, one hundred forty
      dogs and cats anesthetized by the anesthesia service. METHODS: The study was
      divided into two 11.5 month periods. During each period, incidents were logged
      (e.g. closed adjustable pressure limiting (APL) valve, esophageal intubation, and
      medication error). At the end of the first period, four countermeasures were
      incorporated into the service's protocols: 1) prior to any drug injection, the
      individual would read out aloud the drug name, patient name, and route of
      administration; 2) use of a uniquely colored occlusive wrap over arterial
      catheters; 3) a check box on the anesthesia record labeled "Technician Confirmed
      Intubation"; 4) a check box on the anesthesia record labeled "Technician Checked
      OR (operating room)". The number of patient safety incidents during period 1 and
      period 2 were compared using Fisher's Exact Test. RESULTS: During Period 1, there
      were 74 incidents documented in 2028 patients (3.6%) including 25 medication
      errors, 20 closed APL valves, and 16 of esophageal intubation. During Period 2,
      there were 30 incidents documented in 2112 patients (1.4%) including 14
      medication errors, 5 closed APL valves, and 4 of esophageal intubation. The
      proportion of events during Period 2 was significantly smaller than during Period
      1 (p < 0.0001). CONCLUSIONS AND CLINICAL RELEVANCE: Implementation of four simple
      interventions was associated with a significant decrease in the number of
      incidents.

PMID- 24571420
TI  - Identification of the sulfone functionality in protonated analytes via
      ion/molecule reactions in a linear quadrupole ion trap mass spectrometer.
AB  - A tandem mass spectrometric method is presented for the rapid identification of
      drug metabolites that contain the sulfone functional group. This method is based
      on a gas-phase ion/molecule reaction of protonated sulfone analytes with
      trimethyl borate (TMB) that yields a diagnostic product ion, adduct-Me2O, at high
      reaction efficiency. A variety of compounds with different functional groups,
      such as sulfoxides, hydroxylamines, N-oxides, anilines, phenol, an aliphatic
      amine, and an aliphatic alcohol, were examined to probe the selectivity of this
      reaction. Except for protonated sulfones, most of the protonated compounds react
      very slowly or not at all with TMB. Most importantly, none of them give the
      adduct-Me2O product. A mechanism that explains the observed selectivity is
      proposed for the diagnostic reaction and is supported by quantum chemical
      calculations. The reaction was tested with the anti-inflammatory drug sulindac
      and its metabolite, sulindac sulfone, which were readily distinguished. The
      presence of other functionalities in addition to sulfone was found not to
      influence the diagnostic reactivity. 

PMID- 24571421
TI  - Influence of seasonal variations in sea level on the salinity regime of a coastal
      groundwater-fed wetland.
AB  - Seasonal variations in sea level are often neglected in studies of coastal
      aquifers; however, they may have important controls on processes such as
      submarine groundwater discharge, sea water intrusion, and groundwater discharge
      to coastal springs and wetlands. We investigated seasonal variations in salinity
      in a groundwater-fed coastal wetland (the RAMSAR listed Piccaninnie Ponds in
      South Australia) and found that salinity peaked during winter, coincident with
      seasonal sea level peaks. Closer examination of salinity variations revealed a
      relationship between changes in sea level and changes in salinity, indicating
      that sea level-driven movement of the fresh water-sea water interface influences
      the salinity of discharging groundwater in the wetland. Moreover, the seasonal
      control of sea level on wetland salinity seems to override the influence of
      seasonal recharge. A two-dimensional variable density model helped validate this
      conceptual model of coastal groundwater discharge by showing that fluctuations in
      groundwater salinity in a coastal aquifer can be driven by a seasonal coastal
      boundary condition in spite of seasonal recharge/discharge dynamics. Because
      seasonal variations in sea level and coastal wetlands are ubiquitous throughout
      the world, these findings have important implications for monitoring and
      management of coastal groundwater-dependent ecosystems. 

PMID- 24571419
TI  - KPC-3 carbapenemase harbored in FIIk plasmid from Klebsiella pneumoniae ST512 and
      Escherichia coli ST43 in the same patient.
AB  - Five carbapenem-resistant strains (three Klebsiella pneumoniae, one Escherichia
      coli, and one Enterobacter aerogenes) were isolated between 2009 and 2012 at the
      Verona University Hospital, Italy, during an epidemiological analysis of
      antibiotic resistance determinants and plasmid profiles in Enterobacteriaceae.
      Two out of the five strains, K. pneumoniae E530 and E. coli E558, were cultured
      from bile and abdominal drainage, respectively, of a single patient. The strains
      were resistant to beta-lactams and fluoroquinolones, and susceptible to
      tigecycline and colistin. All the strains harboured bla(KPC-3), bla(TEM-1), and
      bla(OXA-9), and the three K. pneumoniae additionally carried blaSHV-11 and
      aac(6')Ib. The bla(KPC-3) was inserted in transposon Tn4401a. All the strains
      hosted an FIIk-type plasmid, and the three K. pneumoniae coharboured an colE-type
      plasmid. Transconjugants, besides bla(KPC-3), harboured bla(TEM-1) and bla(OXA-9)
      genes on FIIk-type plasmid. K. pneumoniae E301 was ST258, while strain E530 and
      C525 belonged to the ST512, and E. coli E558 was ST43. To our best knowledge,
      this is the first report that strongly supports the transmission of bla(KPC-3)
      from ST512 K. pneumoniae to E. coli ST43 in a single patient, a phenomenon of
      both clinical and microbiological importance.

PMID- 24571422
TI  - Comparison of Doppler, oscillometric, auricular and carotid arterial blood
      pressure measurements in isoflurane anesthetized New Zealand white rabbits.
AB  - OBJECTIVE: To assess agreement between carotid arterial pressure and auricular
      arterial, thoracic limb Doppler or thoracic limb oscillometric blood pressure
      measurements. STUDY DESIGN: Prospective experimental study. ANIMALS: Six adult
      New Zealand white rabbits. METHODS: Rabbits were anesthetized with isoflurane in
      oxygen at 1, 1.5 and 2 MAC on two separate occasions. Catheters in the auricular
      and the contralateral external carotid artery were connected to calibrated
      pressure transducers via non-compliant tubing. Inflatable cuffs of width equal to
      approximately 40% of the limb circumference were placed above the carpus on both
      thoracic limbs with a Doppler transducer placed distal to the cuff on one.
      Systolic (SAP) and mean (MAP) arterial blood pressure measurements were obtained
      at each dose, on each occasion. Agreement between measurement techniques was
      evaluated by repeated measures Bland Altman analysis with carotid pressure as the
      reference. Variation in bias over the measurement range was evaluated by
      regression analysis. RESULTS: Carotid MAP and SAP ranged from 20 to 65 mmHg and
      37 to 103 mmHg respectively. Bias and 95% limits of agreement for auricular and
      oscillometric MAP were 7 (0-14) and -5 (-21-11) mmHg, respectively, and for
      auricular, oscillometric and Doppler SAP were 23 (8-37), -2 (-24-20) and 13 (-14
      39) mmHg, respectively. Bias varied significantly over the measurement range (p <
      0.001) for all three SAP techniques but not for MAP measurements. CONCLUSIONS AND
      CLINICAL RELEVANCE: Limits of agreement for all measurements were large but less
      so for MAP than SAP. Variation in bias with SAP should be considered when using
      these measurements clinically.

PMID- 24571424
TI  - Effectiveness of neoadjuvant concurrent chemoradiotherapy versus up-front
      proctectomy in clinical stage II-III rectal cancer: A population-based study.
AB  - AIMS: Neoadjuvant concurrent chemoradiotherapy (NCCRT) is currently the preferred
      treatment for rectal cancer of clinical stage II-III based on its efficacy in
      clinical trials. The population-based effectiveness of NCCRT is rarely reported
      on in the literature. The purpose of our study is to investigate the nationwide
      population-based effectiveness of NCCRT as compared with up-front proctectomy.
      METHODS: In this retrospective cohort study, we identified the study population
      by linking datasets including the cancer registry, death registry and other
      related files in Taiwan. We identified all patients with rectal adenocarcinoma of
      American Joint Committee on Cancer clinical stage II or III who were diagnosed in
      2007 or 2008 and received either NCCRT or up-front proctectomy. We included
      patients' age, gender, residence, socioeconomic status and clinical stage as
      covariables. We used overall survival as the measure of effectiveness. The Cox
      proportional-hazards regression model was used for statistical analyses. We
      further conducted sensitivity analyses, one in only those who received optimal
      postoperative chemotherapy and one in two subgroups matched for propensity score.
      RESULTS: We included 1933 patients (NCCRT: 424; up-front proctectomy: 1509) in
      the study population. NCCRT was associated with improved survival as compared
      with up-front proctectomy (adjusted hazard ratio of death 0.656; 95% confidence
      interval 0.495-0.871). Our results were robust in the sensitivity analyses.
      CONCLUSION: We demonstrated that the use of neoadjuvant concurrent systemic
      therapy and radiotherapy is associated with better effectiveness in rectal
      adenocarcinoma of clinical stage II-III as compared with up-front proctectomy.
      Further studies are needed to elucidate the subgroups most likely to benefit and
      to clarify NCCRT's cost-effectiveness.

PMID- 24571423
TI  - Neck circumference is a predictor of metabolic syndrome and obstructive sleep
      apnea in short-sleeping obese men and women.
AB  - BACKGROUND: The constellation of metabolic syndrome, although controversial with
      regard to its clinical usefulness, is epidemiologically related to increased
      diabetes risk and cardiovascular mortality. Our goal was to investigate the
      associations among neck circumference (NC), obstructive sleep apnea syndromes
      (OSAS), and metabolic syndrome in obese men and women sleeping less than 6.5 hr
      per night. METHODS: This was a cross-sectional study of obese men and
      premenopausal obese women sleeping less than 6.5 hr per night. We enrolled 120
      individuals (92 women), age 40.5+/-6.9 years and body mass index (BMI) 38.6+/-6.5
      kg/m(2). Metabolic syndrome severity was assessed by a score and OSAS was defined
      as a respiratory disturbance index (RDI) >=5. Metabolic end endocrine parameters
      were measured, and sleep duration was determined by actigraphy and validated
      questionnaires. RESULTS: Metabolic syndrome was found in 41% and OSAS in 58% (28%
      had both). Subjects with metabolic syndrome were 3 years older and more often
      Caucasian; they had higher RDI scores, larger NC, more visceral fat, lower serum
      adiponectin, higher 24-hr urinary norepinephrine (NE) excretion, and lower growth
      hormone concentrations. A NC of >=38 cm had a sensitivity of 54% and 58% and a
      specificity of 70% and 79% in predicting the presence of metabolic syndrome and
      OSAS, respectively. RDI, adiponectin, and NC accounted for approximately 30% of
      the variability in the metabolic syndrome score, as estimated by an age-, gender
      , and race-corrected multivariate model (R(2)=0.376, P<0.001). CONCLUSION:
      Greater NC is associated with OSAS and metabolic syndrome in short-sleeping obese
      men and premenopausal obese women. Addition of NC to the definition of metabolic
      syndrome should be considered and needs to be validated in future studies.

PMID- 24571425
TI  - Effects of viscosity and volume on the patterns of esophageal motility in healthy
      adults using high-resolution manometry.
AB  - The purpose of this study was to determine the effects of age, sex, body mass
      index (BMI), viscosity, and volume on esophageal motility using high-resolution
      manometry (HRM). Manometric studies were performed on 60 asymptomatic volunteers
      (27 men and 33 women, age: 19-56 years) while in a supine position. Manometric
      protocol included 10 water swallows (5 cc), 10 jelly swallows (5 cc), and 1 water
      swallow (20 cc). Evaluation of HRM parameters including length of proximal
      pressure trough (PPT length), distal latency (DL), contractile front velocity
      (CFV), distal contractile integral (DCI), and 4-second integrated relaxation
      pressure (IRP) was performed using MATLAB. Significant differences were noted in
      median IRP between water 5 cc (median 7.2 mmHg [range 5.5-9.6]), jelly 5 cc
      (median 6.0 mmHg [range 3.8-8.0]), and water 20 cc {(Median 4.8 mmHg [range 3.3
      7.4]), P < 0.01}. DL were significantly different between water 5 cc, jelly 5 cc,
      and water 20 cc (P < 0.01), and in terms of PPT, proportions of small (2 cm <= <
      5 cm) and large (5 cm<=) break for jelly 5 cc were significantly higher than
      those for the water 5 cc swallow (P < 0.05). Furthermore, DCI increased with age
      for water 5 cc, and a significant negative correlation was noticed between
      proportions of small break and BMI for water 5 cc. Manometric measurements vary
      depending on age, BMI, viscosity, and volume. These findings need to be taken
      into account in the interpretation of manometry results.

PMID- 24571426
TI  - Photoexcited states of UV absorbers, benzophenone derivatives.
AB  - The UV absorption, phosphorescence and phosphorescence-excitation spectra of
      benzophenone (BP) derivatives used as organic UV absorbers have been observed in
      rigid solutions at 77 K. The triplet-triplet absorption spectra have been
      observed in acetonitrile at room temperature. The BP derivatives studied are
      2,2',4,4'-tetrahydroxybenzophenone (BP-2), 2-hydroxy-4-methoxybenzophenone (BP
      3), 2,2'-dihydroxy-4,4'-dimethoxybenzophenone (BP-6), 5-chloro-2
      hydroxybenzophenone (BP-7) and 2-hydroxy-4-n-octyloxybenzophenone (BP-12). The
      energy levels and lifetimes of the lowest excited triplet (T1 ) states of these
      BP derivatives were determined from the first peak of phosphorescence. The time
      resolved near-IR emission spectrum of singlet oxygen generated by
      photosensitization with BP-7 was observed in acetonitrile at room temperature. BP
      2, BP-3, BP-6 and BP-12 show photoinduced phosphorescence enhancement in ethanol
      at 77 K. The possible mechanism of the observed phosphorescence enhancement is
      discussed. The T1 states of 2-hydroxy-5-methylbenzophenone, 4-methoxybenzophenone
      and 2,4'-dimethoxybenzophenone have been studied for comparison. 

PMID- 24571427
TI  - Abacavir forms novel cross-linking abacavir protein adducts in patients.
AB  - Abacavir (ABC), a nucleoside-analogue reverse transcriptase inhibitor, is
      associated with severe hypersensitivity reactions that are thought to involve the
      activation of CD8+ T cells in a HLA-B*57:01-restricted manner. Recent studies
      have claimed that noncovalent interactions of ABC with HLA-B*57:01 are
      responsible for the immunological reactions associated with ABC. However, the
      formation of hemoglobin-ABC aldehyde (ABCA) adducts in patients exposed to ABC
      suggests that protein conjugation might represent a pathway for antigen
      formation. To further characterize protein conjugation reactions, we used mass
      spectrometric methods to define ABCA modifications in patients receiving ABC
      therapy. ABCA formed a novel intramolecular cross-linking adduct on human serum
      albumin (HSA) in patients and in vitro via Michael addition, followed by
      nucleophilic adduction of the aldehyde with a neighboring protein nucleophile.
      Adducts were detected on Lys159, Lys190, His146, and Cys34 residues in the
      subdomain IB of HSA. Only a cysteine adduct and a putative cross-linking adduct
      were detected on glutathione S-transferase Pi (GSTP). These findings reveal that
      ABC forms novel types of antigens in all patients taking the drug. It is
      therefore vital that the immunological consequences of such pathways of
      haptenation are explored in the in vitro models that have been used by various
      groups to define new mechanisms of drug hypersensitivity exemplified by ABC.

PMID- 24571428
TI  - Reply to letter: Age and sex effects on the single- and multiple-dose safety and
      pharmacokinetics of the new renin inhibitor ACT-178882.

PMID- 24571429
TI  - Russian pioneers of therapeutic hemapheresis and extracorporeal hemocorrection:
      100-year anniversary of the world's first successful plasmapheresis.
AB  - On 15 February 2013 (2 February on the Julian Calendar) we celebrated the 100
      year anniversary of the world's first successful experimental plasmapheresis.
      Scientific research projects in this field were carried out by the Department of
      Infectious Disease, Russian Imperial Medical Surgical Academy located in Saint
      Petersburg. Doctor of Medical Sciences and Professor Vadim A. Yurevich was a
      Principal Investigator for this research, which in 1913 resulted in the discovery
      of a new way of treatment. The results were published in Russki Vratch (Russian
      Physician) Journal no. 18 (1914) - V.A. Yurevich and N.K. Rosenberg "For the
      Question Regarding Washing of Blood Outside of the Body and the Vitality of Red
      Blood Cells". There was no terminology offered for this medical innovation at
      that time. Plasma removal was performed not solely, but in combination with
      washing of blood cells returned to the patient. Nowadays this combination is
      still considered to be more effective than separate plasmapheresis. According to
      the published experimental protocols this new treatment was done on 15 February
      (2 February on the Julian Calendar or "old style"). One year later in 1914 a
      famous researcher, John Abel and coauthors, repeated a separate plasma removal
      treatment with retransfusion of the blood cells and suggested the term
      "plasmapheresis", which is now official. The article entitled "Plasma Removal
      With Return of Corpuscles (Plasmapheresis)", written by Abel was published 3
      months later than the article by Professor Yurevich. In 1924, Dr Ivan P.
      Mikhailovskiy repeated experiments by Yurevich and Rosenberg in vivo on a dog
      model, confirmed the clinical efficiency and developed the methodology in his
      article "Washing of Blood In Vivo, the Methodology, Problems, and Importance for
      the Treatment of Toxic Conditions." 

PMID- 24571430
TI  - Carvedilol inhibits the cardiostimulant and thermogenic effects of MDMA in
      humans.

PMID- 24571431
TI  - Total synthesis of neuroprotectin D1 analogues derived from omega-6
      docosapentaenoic acid (DPA) and adrenic acid (AdA) from a common pivotal, late
      stage intermediate.
AB  - The first total synthesis of three omega-6 dihydroxylated (E,E,Z)-docosatrienes
      has been successfully achieved employing a flexible strategy. The key features
      encompass a Boland semireduction, to create the (E,E,Z)-triene via an (E,E)
      ynediene, and a selective deprotection of a tris(tert-butyldimethylsilyl) ether.
      The main advantage of the present strategy over previous syntheses of noncyclic
      dihydroxylated PUFA metabolites derived from docosahexaenoic and arachidonic
      acids comes from the introduction of the polar head chain at the very end of the
      synthesis from an advanced, pivotal aldehyde. In terms of divergency this enables
      late-stage modification of the head group. 

PMID- 24571432
TI  - Gold(I)-catalyzed ring-expanding spiroannulation of cyclopropenones with enynes.
AB  - The gold(I)-catalyzed ring-expanding spiroannulation of cyclopropenones with
      enynes is reported here. A molecule of water is incorporated into the products
      during the spiroannulation to afford spirocyclic cyclopentenones containing an
      alcohol functionality. 

PMID- 24571433
TI  - Choice of primary outcomes in randomised trials and systematic reviews evaluating
      interventions for preterm birth prevention: a systematic review.
AB  - BACKGROUND: The inappropriate and inconsistent selection of primary outcomes
      (POs) in randomised controlled trials (RCTs) and systematic reviews (SRs) can
      make evidence difficult to interpret, limiting its usefulness to inform clinical
      practice. OBJECTIVES: To systematically review the choice and consistency of POs
      in RCTs and SRs of preventative interventions for preterm birth. SEARCH STRATEGY:
      Cochrane Pregnancy and Childbirth Group's Specialised Register of trials and a
      full list of published reviews and protocols. SELECTION CRITERIA: Full reports of
      RCTs for preterm birth prevention published after CONSORT (January 1997-January
      2011), and Cochrane Reviews and protocols relevant to preterm birth prevention,
      for the same period. DATA COLLECTION AND ANALYSIS: For RCTs, the PO was the
      outcome used for sample size calculation. For SRs, we included all outcomes
      listed as 'primary'. Two review authors selected studies and double-checked the
      data for accuracy. RESULTS: Seventy-two different POs were reported by 103 RCTs.
      The three most common POs were based on length of gestation, with preterm birth
      before 37 weeks of gestation being the most common (18/103, 18%). Few RCTs chose
      perinatal morbidity (4/103) or mortality (1/103), or their composites (5/103), as
      POs. In 33 Cochrane Reviews, 29 different POs were reported. The three most
      common POs were based on death or morbidity in the baby, with death of the baby
      being the most common (22/33, 67%). POs were variably defined. CONCLUSIONS: There
      is a lack of consistency in the choice and definitions of POs in clinical
      research related to preterm birth prevention. SRs are more likely to report
      morbidity and mortality as POs, whereas RCTs tend to use length of gestation.
      Researchers are urged to review the outcomes reported in RCTs and SRs in their
      respective areas of interest to highlight discrepancies and facilitate the
      development of core outcome sets.

PMID- 24571434
TI  - A perspective on physical organic chemistry.
AB  - A perspective on the development of mechanistic carbene chemistry is presented.
      The author will point out questions that have been answered, and a next
      generation of questions will be proposed. 

PMID- 24571436
TI  - Diazirine-containing RNA photo-cross-linking probes for capturing microRNA
      targets.
AB  - Here, we report the applicability of diazirine-containing RNA photo-cross-linking
      probes for the identification of microRNA (miRNA) targets. The RNA cross-linking
      probes were synthesized by substituting the RNA nucleobases with nucleoside
      analogues such as 1-O-[3-(3-trifluoromethyl-3H-diazirin-3-yl)]benzyl-beta-d
      ribofuranose or 1-O-[4-(3-trifluoromethyl-3H-diazirin-3-yl)]benzyl-beta-D
      ribofuranose that carry aryl trifluoromethyl diazirine moieties. The probes were
      successfully cross-linked with synthetic RNAs containing the four natural
      nucleosides on the opposite site of the nucleoside analogues. Furthermore, it was
      found that miRNAs containing these analogues were effective in regulating the
      expression of their target genes. Thus, RNAs containing the nucleoside analogues
      are promising candidates as photo-cross-linking probes to identify the target
      mRNAs of miRNAs.

PMID- 24571435
TI  - Plasma biomarkers profile of female dogs with mammary carcinoma and its
      association with clinical and pathological features.
AB  - The immunological biomarkers profiles were evaluated using Luminex as putative
      measures to monitor canine mammary carcinomas (MCs). Forty female dogs were
      categorized into benign mixed tumour (MC-BMT = 28) and mammary carcinoma (MC=12).
      The ascendant biomarker signatures were used to compare the groups. For example,
      a higher frequency of MC-BMT animals producing IL-6, CXCL-8 and CXCL-10 was
      observed, whereas for the MC group IL-2 and CXCL-8 were detected. MC-BMT animals
      without metastasis had an increase in the levels of IL-2, CXCL-8, CXCL-10, IL-6,
      TNF-alpha, IL-15 and a decrease in IL-10 and CXCL-8. MC-BMT animals with
      metastasis showed only an increase in CXCL-10 and a decrease in IL-18. After
      comparing the ascendant signatures following the presence of metastasis in both
      groups, a higher frequency of dogs exhibiting IL-10 production was observed.
      Pearson correlation (P = 0.0273) and receiver operating characteristic (ROC)
      curve analysis revealed that this pattern was associated with worse outcome and
      lower survival rates in MC animals. 

PMID- 24571437
TI  - Dimerization of resveratrol induced by red light and its synergistic analgesic
      effects with cobra neurotoxin.
AB  - Resveratrol polymer has better effects than monomer in some aspects as reported,
      but most of synthetic methods acquire severe conditions and no analgesic effects
      are investigated. A novel method is found to synthesize resveratrol polymer by
      excitation of photosensitizer pheophorbide at red light of 630 nm. The polymer
      was analyzed by fluorescence spectra and HPLC, further isolated by preparative
      liquid chromatography and identified as a resveratrol dimer by MS and NMR.
      Analgesic effects were measured by acetic acid writhing and hot-plate test in
      mice. The resveratrol dimer has the stronger analgesic effects than monomer, and
      drug combination of the dimer and cobra neurotoxin enhances and prolongs
      analgesic effects, suggesting the synergistic action. Simulation of molecular
      interaction reveals that the dimer spontaneously binds to cobra neurotoxin and
      makes a complex substance. The dimer can interact with cyclooxygenase-2, MU
      receptor and nicotine receptor, the synergistic analgesic effects of the complex
      are attributed to its multiple targets role. The combination of resveratrol dimer
      and cobra neurotoxin may make up for their deficiencies in analgesic effects, and
      has prospects in clinical use.

PMID- 24571438
TI  - Tyrosine 263 in cyanobacterial phytochrome Cph1 optimizes photochemistry at the
      prelumi-R->lumi-R step.
AB  - We report a low-temperature fluorescence spectroscopy study of the PAS-GAF-PHY
      sensory module of Cph1 phytochrome, its Y263F mutant (both with known 3D
      structures) as well as Y263H and Y263S to connect their photochemical parameters
      with intramolecular interactions. None of the holoproteins showed photochemical
      activity at low temperature, and the activation barriers for the Pr->lumi-R
      photoreaction (2.5-3.1 kJ mol(-1)) and fluorescence quantum yields (0.29-0.42)
      were similar. The effect of the mutations on Pr->Pfr photoconversion efficiency
      (PhiPr->Pfr) was observed primarily at the prelumi-R S0 bifurcation point
      corresponding to the conical intersection of the energy surfaces at which the
      molecule relaxes to form lumi-R or Pr, lowering PhiPr->Pfr from 0.13 in the wild
      type to 0.05-0.07 in the mutants. We suggest that the Ea activation barrier in
      the Pr* S1 excited state might correspond to the D-ring (C19) carbonyl - H290
      hydrogen bond or possibly to the hindrance caused by the C13(1) /C17(1) methyl
      groups of the C and D rings. The critical role of the tyrosine hydroxyl group can
      be at the prelumi-R bifurcation point to optimize the yield of the photoprocess
      and energy storage in the form of lumi-R for subsequent rearrangement processes
      culminating in Pfr formation.

PMID- 24571440
TI  - Membrane damage efficiency of phenothiazinium photosensitizers.
AB  - Structure-activity relationships have been widely reported for porphyrin and
      phthalocyanine photosensitizers, but not for phenothiazinium derivatives. Here,
      four phenothiazinium salts (methylene blue, toluidine blue O, 1,9-dimethyl
      methylene blue and the pentacyclic derivative DO15) were used to investigate how
      the ability to damage membranes is affected by membrane/solution partition,
      photophysical properties and tendency to aggregation of the photosensitizer.
      These two latter aspects were studied both in isotropic solutions and in
      membranes. Membrane damage was assessed by leakage of a fluorescent probe
      entrapped in liposomes and by generation of thiobarbituric acid-reactive species
      (TBARS), while structural changes at the lipid bilayer were detected by small
      angle X-ray scattering. We observed that all compounds had similar singlet-oxygen
      quantum yields in ethanol, but only the photosensitizers that had higher
      membrane/solution partition (1,9-dimethyl methylene blue and DO15, the latter
      having the higher value) could permeabilize the lipid bilayer. Moreover, of these
      two photosensitizers, only DO15 altered membrane structure, a result that was
      attributed to its destabilization of higher order aggregates, generation of
      higher amounts of singlet oxygen within the membranes and effective electron
      transfer reaction within its dimers. We concluded that membrane-based protocols
      can provide a better insight on the photodynamic efficiency of the
      photosensitizer. 

PMID- 24571441
TI  - Successful use of tocilizumab in a case of multicentric Castleman's disease and
      end-stage renal disease.

PMID- 24571439
TI  - Genome-wide association analyses of child genotype effects and parent-of-origin
      effects in specific language impairment.
AB  - Specific language impairment (SLI) is a neurodevelopmental disorder that affects
      linguistic abilities when development is otherwise normal. We report the results
      of a genome-wide association study of SLI which included parent-of-origin effects
      and child genotype effects and used 278 families of language-impaired children.
      The child genotype effects analysis did not identify significant associations. We
      found genome-wide significant paternal parent-of-origin effects on chromosome
      14q12 (P = 3.74 * 10(-8)) and suggestive maternal parent-of-origin effects on
      chromosome 5p13 (P = 1.16 * 10(-7)). A subsequent targeted association of six
      single-nucleotide-polymorphisms (SNPs) on chromosome 5 in 313 language-impaired
      individuals and their mothers from the ALSPAC cohort replicated the maternal
      effects, albeit in the opposite direction (P = 0.001); as fathers' genotypes were
      not available in the ALSPAC study, the replication analysis did not include
      paternal parent-of-origin effects. The paternally-associated SNP on chromosome 14
      yields a non-synonymous coding change within the NOP9 gene. This gene encodes an
      RNA-binding protein that has been reported to be significantly dysregulated in
      individuals with schizophrenia. The region of maternal association on chromosome
      5 falls between the PTGER4 and DAB2 genes, in a region previously implicated in
      autism and ADHD. The top SNP in this association locus is a potential expression
      QTL of ARHGEF19 (also called WGEF) on chromosome 1. Members of this protein
      family have been implicated in intellectual disability. In summary, this study
      implicates parent-of-origin effects in language impairment, and adds an
      interesting new dimension to the emerging picture of shared genetic etiology
      across various neurodevelopmental disorders.

PMID- 24571442
TI  - Comparison of open, laparoscopic, and hand-assisted laparoscopic
      devascularization of the upper stomach and splenectomy for treatment of
      esophageal and gastric varices: a single-center experience.
AB  - INTRODUCTION: Laparoscopic devascularization of the upper stomach and splenectomy
      (Dev+Sp), is technically difficult in patients with portal hypertension because
      of enlarged collateral vessels and spleen. This report presents the efficacy and
      safety of hand-assisted laparoscopic (HALS) Dev+Sp. METHODS: Ten patients
      underwent HALS Dev+Sp as a treatment for esophagogastric varices between 2005 and
      2012 (HALS group). A vessel-sealing system was used for devascularization of
      vessels. An autosuture device was applied to dissect the splenic hilum and the
      left gastric and enlarged short gastric vessels. The operative and postoperative
      data were compared between patients who previously underwent laparoscopic Dev+Sp
      (LAP group, n = 9) and conventional Dev+Sp (OP group, n = 10) between 2001 and
      2008. RESULTS: The mean operative time was 328, 336, and 245 min (P < 0.05) and
      the mean blood loss was 1786, 981, and 250 mL (P < 0.05) in the OP, LAP, and HALS
      groups, respectively. Laparoscopic surgery was converted to HALS in one patient
      and to open surgery in three patients. There were no conversions in the HALS
      group. There was no significant difference in the cumulative recurrence rate and
      bleeding rate in the groups. CONCLUSION: HALS Dev+Sp is a feasible and effective
      surgery in patients with portal hypertension.

PMID- 24571444
TI  - Role of GAD2 and HTR1B genes in early-onset obsessive-compulsive disorder:
      results from transmission disequilibrium study.
AB  - One of the leading biological models of obsessive-compulsive disorder (OCD) is
      the frontal-striatal-thalamic model. This study undertakes an extensive
      exploration of the variability in genes related to the regulation of the frontal
      striatal-thalamic system in a sample of early-onset OCD trios. To this end, we
      genotyped 266 single nucleotide polymorphisms (SNPs) in 35 genes in 84 OCD
      probands and their parents. Finally, 75 complete trios were included in the
      analysis. Twenty SNPs were overtransmitted from parents to early-onset OCD
      probands and presented nominal pointwise P < 0.05 values. Three of these
      polymorphisms achieved P < 2 * 10(-4), the significant P-value after Bonferroni
      corrections: rs8190748 and rs992990 localized in GAD2 and rs2000292 in HTR1B.
      When we stratified our sample according to gender, different trends were observed
      between males and females. In males, SNP rs2000292 (HTR1B) showed the lowest P
      value (P = 0.0006), whereas the SNPs in GAD2 were only marginally significant (P
      = 0.01). In contrast, in females HTR1B polymorphisms were not significant,
      whereas rs8190748 (GAD2) showed the lowest P-value (P = 0.0006). These results
      are in agreement with several lines of evidence that indicate a role for the
      serotonin and gamma-Aminobutyric acid (GABA) pathways in the risk of early-onset
      OCD and with the gender differences in OCD pathophysiology reported elsewhere.
      However, our results need to be replicated in studies with larger cohorts in
      order to confirm these associations.

PMID- 24571445
TI  - Measuring exposure to solar ultraviolet radiation using a dosimetric technique:
      understanding participant compliance issues.
AB  - Personal ultraviolet dosimeters have been used in epidemiological studies to
      understand the risks and benefits of individuals' exposure to solar ultraviolet
      radiation (UVR). We investigated the types and determinants of noncompliance
      associated with a protocol for use of polysulphone UVR dosimeters. In the AusD
      Study, 1002 Australian adults (aged 18-75 years) were asked to wear a new
      dosimeter on their wrist each day for 10 consecutive days to quantify their daily
      exposure to solar UVR. Of the 10 020 dosimeters distributed, 296 (3%) were not
      returned or used (Type-I noncompliance) and other usage errors were reported for
      763 (8%) returned dosimeters (Type-II noncompliance). Type-I errors were more
      common in participants with predominantly outdoor occupations. Type-II errors
      were reported more frequently on the first day of measurement; weekend days or
      rainy days; and among females; younger people; more educated participants or
      those with outdoor occupations. Half (50%) the participants reported a
      noncompliance error on at least 1 day during the 10-day period. However, 92% of
      participants had at least 7 days of usable data without any apparent
      noncompliance issues. The factors identified should be considered when designing
      future UVR dosimetry studies.

PMID- 24571443
TI  - Impaired neurogenesis by HIV-1-Gp120 is rescued by genetic deletion of fatty acid
      amide hydrolase enzyme.
AB  - BACKGROUND AND PURPOSE: The HIV-envelope glycoprotein Gp120 is involved in
      neuronal injury and is associated with neuro-AIDS pathogenesis in the brain.
      Endocannabinoids are important lipid ligands in the CNS regulating neural
      functions, and their degeneration is controlled by hydrolysing enzymes such as
      the fatty acid amide hydrolase (FAAH). Here, we examined whether in vivo genetic
      deletion of Faah gene prevents HIV-1 Gp120-mediated effects on neurogenesis.
      EXPERIMENTAL APPROACH: We generated new GFAP/Gp120 transgenic (Tg) mice that have
      genetic deletion of Faah gene by mating glial fribillary acidic protein
      (GFAP)/Gp120 Tg mice with Faah-/- mice. Neurogenesis and cell death were assessed
      by immunocytochemical analysis. KEY RESULTS: Endocannabinoid levels in the brain
      of the double GFAP/Gp120//Faah-/- mice were similar to those observed in Faah-/-
      mice. However, unlike the impaired neurogenesis observed in GFAP/Gp120 Tg mice
      and Faah-/- mice, these GFAP/Gp120//Faah-/ mice showed significantly improved
      neurogenesis in the hippocampus, indicated by a significant increase in
      neuroblasts and neuronal cells, an increase in BrdU(+) cells and doublecortin
      positive cells (DCX(+) ), and an increase in the number of PCNA. Furthermore, a
      significant decrease in astrogliosis and gliogenesis was observed in
      GFAP/Gp120//Faah-/-mice and neurogenesis was stimulated by neural progenitor
      cells (NPCs) and/or the newly formed NPC niches characterized by increased COX-2
      expression and elevated levels of PGE2 . CONCLUSIONS AND IMPLICATIONS: In vivo
      genetic ablation of Faah, resulted in enhanced neurogenesis through modulation of
      the newly generated NPC niches in GFAP/Gp120//Faah-/- mice. This suggests a novel
      approach of using FAAH inhibitors to enhance neurogenesis in HIV-1 infected
      brain.

PMID- 24571446
TI  - Low hemoglobin levels and hypo-responsiveness to erythropoiesis-stimulating agent
      associated with poor survival in incident Japanese hemodialysis patients.
AB  - Although erythropoiesis-stimulating agents (ESAs) are effective at treating
      anemia, the association between hemoglobin (Hb) levels and survival is still
      unclear, especially for the incident Japanese hemodialysis (HD) population. The
      Japan Erythropoietin Treatment (JET) Study is an open multi-center, prospective,
      observational study designed to evaluate the relationship between the maintenance
      of Hb levels and new HD patient prognosis after the first administration of
      epoetin beta. Landmark analyses were performed to examine the relationship
      between Hb levels at 6 months and survival. Among a total of 10,310 patients,
      6631 completed the initial 6 months of epoetin beta treatment (induction phase)
      and were followed up for a further 2.5 years (maintenance phase). Three-year
      survival rate of patients with <9 g/dL Hb levels after 6 months was 74.1%, which
      was significantly lower than 89.3% for patients with Hb levels 10 to 11 g/dL; the
      adjusted hazard ratio (HR) was 2.08 (95% CI, 1.57-2.77; P < 0.0001). Moreover,
      the 3-year survival rate for poor responders defined by Hb levels <10 g/dL and
      weekly epoetin beta doses >= 9000 IU during the induction phase was 71.6%, which
      was significantly lower than 89.4% for the group, which had Hb levels 10 to 11
      g/dL excluding poor responders and those with excursion; the HR was 1.71 (95% CI,
      1.13-2.60; P = 0.0118). Adverse events related to the treatment were reported in
      71 of 10,310 patients (0.69%). These findings suggest that the achieved low Hb
      levels and poor response to ESA therapy are significantly associated with high
      mortality.

PMID- 24571447
TI  - Evaluation of Screening Assays for the Detection of Influenza A Virus Serum
      Antibodies in Swine.
AB  - Increased surveillance of influenza A virus (IAV) infections in human and swine
      populations is mandated by public health and animal health concerns. Antibody
      assays have proven useful in previous surveillance programmes because antibodies
      provide a record of prior exposure and the technology is inexpensive. The
      objective of this research was to compare the performance of influenza serum
      antibody assays using samples collected from pigs (vaccinated or unvaccinated)
      inoculated with either A/Swine/OH/511445/2007 gamma H1N1 virus or
      A/Swine/Illinois/02907/2009 Cluster IV H3N2 virus and followed for 42 days.
      Weekly serum samples were tested for anti-IAV antibodies using homologous and
      heterologous haemagglutination-inhibition (HI) assays, commercial swine influenza
      H1N1 and H3N2 indirect ELISAs, and a commercial influenza nucleoprotein (NP)
      blocking ELISA. The homologous HIs showed 100% diagnostic sensitivity, but
      largely failed to detect infection with the heterologous virus. With diagnostic
      sensitivities of 1.4% and 4.9%, respectively, the H1N1 and H3N2 indirect ELISAs
      were ineffective at detecting IAV antibodies in swine infected with the
      contemporary influenza viruses used in the study. At a cut-off of S/N <= 0.60,
      the sensitivity and specificity of the NP-blocking ELISA were estimated at 95.5%
      and 99.6%, respectively. Statistically significant factors which affected S/N
      results include vaccination status, inoculum (virus subtype), day post
      inoculation and the interactions between those factors (P < 0.0001). Serum
      antibodies against NP provide an ideal universal diagnostic screening target and
      could provide a cost-effective approach for the detection and surveillance of IAV
      infections in swine populations.

PMID- 24571449
TI  - [Abstracts of the Annual Meeting of the North German Dermatologic Society,
      February 28-March 1, 2014 Hamburg, Germany].

PMID- 24571451
TI  - Identifying environmental variables explaining genotype-by-environment
      interaction for body weight of rainbow trout (Onchorynchus mykiss): reaction norm
      and factor analytic models.
AB  - BACKGROUND: Identifying the relevant environmental variables that cause GxE
      interaction is often difficult when they cannot be experimentally manipulated.
      Two statistical approaches can be applied to address this question. When data on
      candidate environmental variables are available, GxE interaction can be
      quantified as a function of specific environmental variables using a reaction
      norm model. Alternatively, a factor analytic model can be used to identify the
      latent common factor that explains GxE interaction. This factor can be correlated
      with known environmental variables to identify those that are relevant.
      Previously, we reported a significant GxE interaction for body weight at harvest
      in rainbow trout reared on three continents. Here we explore their possible
      causes. METHODS: Reaction norm and factor analytic models were used to identify
      which environmental variables (age at harvest, water temperature, oxygen, and
      photoperiod) may have caused the observed GxE interaction. Data on body weight at
      harvest was recorded on 8976 offspring reared in various locations: (1) a
      breeding environment in the USA (nucleus), (2) a recirculating aquaculture system
      in the Freshwater Institute in West Virginia, USA, (3) a high-altitude farm in
      Peru, and (4) a low-water temperature farm in Germany. Akaike and Bayesian
      information criteria were used to compare models. RESULTS: The combination of
      days to harvest multiplied with daily temperature (Day*Degree) and photoperiod
      were identified by the reaction norm model as the environmental variables
      responsible for the GxE interaction. The latent common factor that was identified
      by the factor analytic model showed the highest correlation with Day*Degree.
      Day*Degree and photoperiod were the environmental variables that differed most
      between Peru and other environments. Akaike and Bayesian information criteria
      indicated that the factor analytical model was more parsimonious than the
      reaction norm model. CONCLUSIONS: Day*Degree and photoperiod were identified as
      environmental variables responsible for the strong GxE interaction for body
      weight at harvest in rainbow trout across four environments. Both the reaction
      norm and the factor analytic models can help identify the environmental variables
      responsible for GxE interaction. A factor analytic model is preferred over a
      reaction norm model when limited information on differences in environmental
      variables between farms is available.

PMID- 24571450
TI  - Hemoglobin A1c in patients on peritoneal dialysis: how should we interpret it?
AB  - Almost half the patients on peritoneal dialysis are diabetic and glycemic control
      is essential to improve both patient and technique survival. Hemoglobin A1c
      (HbA1c) is widely used in the general population for diabetes diagnosis and
      monitoring as it highly correlates with blood glucose levels and outcomes. Its
      use has been extrapolated to the peritoneal dialysis population, despite HbA1c
      being commonly underestimated. In renal failure patients, HbA1c is influenced by
      variables affecting not only glycemia but also hemoglobin and the time of
      interaction between the two. Importantly, the impact of these variables differs
      in peritoneal dialysis compared to non-dialysis chronic kidney disease and
      hemodialysis patients. Although HbA1c in peritoneal dialysis patients is less
      directly associated with blood glucose levels than in the general population,
      studies have confirmed its association with patient mortality. In this paper we
      review the variables that can influence HbA1c value emphasizing their impact in
      peritoneal dialysis patients. By providing clinicians with a comprehensive
      understanding of HbA1c results, we provide them with tools for a better patient
      management care and potential improved outcomes of peritoneal dialysis patients. 

PMID- 24571454
TI  - I. Introduction.

PMID- 24571448
TI  - Targeting Rho-GTPases in immune cell migration and inflammation.
AB  - Leukocytes are unmatched migrators capable of traversing barriers and tissues of
      remarkably varied structural composition. An effective immune response relies on
      the ability of its constituent cells to infiltrate target sites. Yet, unwarranted
      mobilization of immune cells can lead to inflammatory diseases and tissue damage
      ranging in severity from mild to life-threatening. The efficacy and plasticity of
      leukocyte migration is driven by the precise spatiotemporal regulation of the
      actin cytoskeleton. The small GTPases of the Rho family (Rho-GTPases), and their
      immediate downstream effector kinases, are key regulators of cellular actomyosin
      dynamics and are therefore considered prime pharmacological targets for stemming
      leukocyte motility in inflammatory disorders. This review describes advances in
      the development of small-molecule inhibitors aimed at modulating the Rho-GTPase
      centric regulatory pathways governing motility, many of which stem from studies
      of cancer invasiveness. These inhibitors promise the advent of novel treatment
      options with high selectivity and potency against immune-mediated pathologies.
      LINKED ARTICLES: This article is part of a themed section on Cytoskeleton,
      Extracellular Matrix, Cell Migration, Wound Healing and Related Topics. To view
      the other articles in this section visit
      http://dx.doi.org/10.1111/bph.2014.171.issue-24.

PMID- 24571452
TI  - ABT-263 enhances sorafenib-induced apoptosis associated with Akt activity and the
      expression of Bax and p21((CIP1/WAF1)) in human cancer cells.
AB  - BACKGROUND AND PURPOSE: Sorafenib, a potent inhibitor that targets several
      kinases associated with tumourigenesis and cell survival, has been approved for
      clinical treatment as a single agent. However, combining sorafenib with other
      agents improves its anti-tumour efficacy in various preclinical tumour models.
      ABT-263, a second-generation BH3 mimic, binds to the anti-apoptotic family
      members Bcl-2, Bcl-xL and Bcl-w, and has been demonstrated to enhance TNFSF10
      (TRAIL)-induced apoptosis in human hepatocarcinoma cells. Hence, we investigated
      the effects of ABT-263 treatment combined with sorafenib. EXPERIMENTAL APPROACH:
      The effects of ABT-263 combined with sorafenib were investigated in vitro, on
      cell viability, clone formation and apoptosis, and the mechanism examined using
      western blot and flow cytometry. This combination was also evaluated in vivo, in
      a mouse xenograft model; tumour growth, volume and weights were measured and a
      TUNEL assay performed. KEY RESULTS: ABT-263 enhanced sorafenib-induced apoptosis
      while sparing non-tumourigenic cells. Although ABT-263 plus sorafenib
      significantly stimulated intracellular reactive oxygen species production and
      subsequent mitochondrial depolarization, this was not sufficient to trigger cell
      apoptosis. ABT-263 plus sorafenib significantly decreased Akt activity, which
      was, at least partly, involved in its effect on apoptosis. Bax and p21
      (CIP1/WAF1) were shown to play a critical role in ABT-263 plus sorafenib-induced
      apoptosis. Combining sorafenib with ABT-263 dramatically increased its efficacy
      in vivo. CONCLUSION AND IMPLICATIONS: The anti-tumour activity of ABT-263 plus
      sorafenib may involve the induction of intrinsic cell apoptosis via inhibition of
      Akt, and reduced Bax and p21 expression. Our findings offer a novel effective
      therapeutic strategy for tumour treatment.

PMID- 24571455
TI  - II. European Americans in Centerville: community and family contexts.

PMID- 24571456
TI  - III. Affective dimensions of death: children's books, questions, and
      understandings.

PMID- 24571457
TI  - IV. Cognitive dimensions of death in context.

PMID- 24571453
TI  - Ginsenoside Rb3 attenuates oxidative stress and preserves endothelial function in
      renal arteries from hypertensive rats.
AB  - BACKGROUND AND PURPOSE: Panax ginseng is commonly used to treat cardiovascular
      conditions in Oriental countries. This study investigated the mechanisms
      underlying the vascular benefits of ginsenoside Rb3 (Rb3) in hypertension.
      EXPERIMENTAL APPROACH: Rings of renal arteries were prepared from spontaneously
      hypertensive rats (SHRs) and normotensive Wistar-Kyoto (WKY) rats and were
      cultured ex vivo for 8 h. Contractile responses of the rings were assessed with
      myograph techniques. Expression of NADPH oxidases was assessed by Western
      blotting and immunohistochemistry. Reactive oxygen species (ROS) were measured
      using dihydroethidium fluorescence imaging and production of NO was determined
      using the fluorescent NO indicator DAF-FM diacetate in human umbilical vein
      endothelial cells. KEY RESULTS: Ex vivo treatment with Rb3 concentration
      dependently augmented endothelium-dependent relaxations, suppressed endothelium
      dependent contractions and reduced ROS production and expressions of NOX-2, NOX-4
      and p67(phox) in arterial rings from SHR. Rb3 treatment also normalized
      angiotensin II (Ang II)-stimulated elevation in ROS and expression of NOX-2 and
      NOX-4 in arterial rings from WKY rats. Rb3 inhibited Ang II-induced reduction of
      NO production and phosphorylation of endothelial NOS in cultures of human
      umbilical vein endothelial cells. Rb3 also inhibited oxidative stress in renal
      arterial rings from hypertensive patients or in Ang II-treated arterial rings
      from normotensive subjects. CONCLUSION AND IMPLICATIONS: Ex vivo Rb3 treatment
      restored impaired endothelial function in arterial rings from hypertensives by
      reversing over-expression of NADPH oxidases and over-production of ROS, and
      improved NO bioavailability. Our findings suggest that medicinal plants
      containing Rb3 could decrease oxidative stress and protect endothelial function
      in hypertension.

PMID- 24571458
TI  - V. Cognitive models of death.

PMID- 24571459
TI  - VI. Mexican American immigrants in the Centerville Region: teachers, children,
      and parents.

PMID- 24571460
TI  - VII. Final thoughts.

PMID- 24571465
TI  - Diversity in children's understanding of death.
AB  - Rosengren, Miller, Gutierrez, Chow, Schein, and Anderson have written a powerful
      and important monograph focused on the fascinating topic of children's
      understanding of death. Combining multiple methods, converging data sources, and
      diverse theoretical approaches, their findings tell us that children may know
      more about death than their parents expect, that even children within a given
      community vary a great deal in their access to information about death, and that
      children's reasoning about life and death is related to the views of those around
      them. Their work highlights children's active role in their own cognitive
      development while showing how children's thinking is embedded in both cultural
      practices and religious ideas. This commentary discusses four topics highlighted
      in the monograph: the value of taking a sociocultural approach to studying
      development, the relative avoidance of religion in cognitive developmental
      research, potential pitfalls of cultural comparison, and the generative notion
      that conflicting ideas on a topic are likely to coexist in the same minds. The
      discussion highlights positive contributions of this monograph, raises critical
      concerns, and suggests future research directions. 

PMID- 24571470
TI  - Risk factors for severe anaemia during telaprevir-based triple therapy: is
      acquired renal dysfunction the missing link?

PMID- 24571472
TI  - Mixed chimerism in haemoglobinopathies: from risk of graft rejection to immune
      tolerance.
AB  - Mixed chimerism (MC), the simultaneous presence of both host- and donor-derived
      cells in the recipient, is observed in a large proportion of patients after
      haematopoietic stem cell transplant (HSCT) to treat haemoglobinopathies. Detected
      early after transplantation, MC often moves towards complete chimerism, although
      sometimes it may evolve into graft rejection, especially if the proportion of
      donor cells is very low. However, some patients develop stable MC, defined as
      persistent when donor- and host-derived cells coexist for periods longer than 2
      years after HSCT. Patients with persistent mixed chimerism (PMC) do not require
      additional red blood cell support and, regardless of the presence in some cases
      of an extremely low percentage of donor-derived nucleated cells in the bone
      marrow, their condition is clinically controlled by an incomplete but functional
      graft, as they express a two- to fivefold enrichment of donor-derived mature
      erythrocytes in the peripheral blood. These findings have tremendous implications
      not only in the context of allogeneic HSCT but also in the design of gene therapy
      trials based on the autologous transplantation of genetically modified CD34+
      cells. Recent studies have shown that durable allograft tolerance has been
      achieved by induction of haematopoietic chimerism in clinical kidney
      transplantation, showing the involvement of regulatory T cells. Similarly, it has
      been shown that the regulatory T cells play a pivotal role in promoting and
      maintaining immune tolerance in patients that develop a status of PMC after HSCT
      for Thalassemia. 

PMID- 24571471
TI  - IL-17A regulates Eimeria tenella schizont maturation and migration in avian
      coccidiosis.
AB  - Although IL17A is associated with the immunological control of various infectious
      diseases, its role in host response to Eimeria infections is not well understood.
      In an effort to better dissect the role of IL17A in host-pathogen interactions in
      avian coccidiosis, a neutralizing antibody (Ab) to chicken IL17A was used to
      counteract IL17A bioactivity in vivo. Chickens infected with Eimeria tenella and
      treated intravenously with IL17A Ab, exhibited reduced intracellular schizont and
      merozoite development, diminished lesion score, compared with untreated controls.
      Immunohistological evaluation of cecal lesions in the parasitized tissues
      indicated reduced migration and maturation of second-generation schizonts and
      reduced lesions in lamina propria and submucosa. In contrast, untreated and
      infected chickens had epithelial cells harboring second-generation schizonts,
      which extend into the submucosa through muscularis mucosa disruptions, maturing
      into second generation merozoites. Furthermore, IL17A Ab treatment was associated
      with increased parameters of Th1 immunity (IL2- and IFNgamma- producing cells),
      reduced levels of reactive oxygen species (ROS), and diminished levels of serum
      matrix metalloproteinase-9 (MMP-9). Finally, schizonts from untreated and
      infected chickens expressed S100, Wiskott-Aldrich syndrome protein family member
      3 (WASF3), and heat shock protein-70 (HSP70) proteins as merozoites matured,
      whereas the expression of these proteins was absent in IL17A Ab-treated chickens.
      These results provide the first evidence that the administration of an IL17A
      neutralizing Ab to E. tenella-infected chickens inhibits the migration of
      parasitized epithelial cells, markedly reduces the production of ROS and MMP-9,
      and decreases cecal lesions, suggesting that IL17A might be a potential
      therapeutic target for coccidiosis control.

PMID- 24571473
TI  - The presence of KIR2DS5 confers protection against adult immune thrombocytopenia.
AB  - Immune thrombocytopenia (ITP) is an autoimmune disorder of unknown aetiology,
      characterised by an isolated low platelet count in the absence of other
      identifiable causes. Genes influencing activation of the immune system have been
      identified as influencing predisposition. Killer cell immunoglobulin-like
      receptors (KIR) control T-cell and natural killer (NK) cell function via
      inhibitory and activating signalling pathways. The inhibitory KIR2DL3, KIR3DL2
      and KIR3DL1 are up-regulated in the T-cells of patients with ITP in remission
      relative to those with active disease, and an association of KIR2DS2 and KIR2DL2
      with ITP has also been reported. No comprehensive KIR analysis in ITP has been
      reported. We performed genotyping of all currently known KIR genes using sequence
      specific primer polymerase chain reaction (SSP-PCR) on a cohort of 83 adult
      patients with ITP (chronic/persistent or relapsed primary ITP identified by
      defined criteria) and 106 age matched healthy white volunteers. Non-white
      patients were not included in the analysis. There was an over-representation of
      KIR2DS3 (known to be in linkage disequilibrium with KIR2DS2 and 2DL2) and under
      representation of KIR2DS5 (also protective against other immune mediated
      disorders) in adult ITP [odds ratio (OR) = 0.16, confidence interval (CI) 0.08
      0.32, P < 0.001]. By multivariable binary logistic regression to adjust for age,
      sex and the effects of other KIR genes, the presence of KIR2DS2/2DL2 with KIR2DS5
      abrogated the risk of KIR2DS2/2DL2 and the protective benefit of KIR2DS5. Further
      studies are required to establish the mechanistic basis for these observations
      and their potential impact on ITP therapy. 

PMID- 24571474
TI  - HLA-G 14 bp deletion/insertion polymorphism and mother-to-child transmission of
      HIV.
AB  - The human leukocyte antigen HLA-G, highly expressed at the maternal-fetal
      interface, has a pivotal role in mediating immune tolerance. In this study we
      investigated the influence of HLA-G 14 bp insertion polymorphism in human
      immunodeficiency virus (HIV)-1 mother-to-child HIV-1 transmission. The 14 bp
      insertion polymorphism was analyzed among 99 HIV-1 positive mothers and 329
      infants born to HIV-positive mothers in Zambia, among whom vertical transmission
      status and timing had been determined. HLA-G 14 bp insertion polymorphism was
      detected using a custom TaqMan single nucleotide polymorphisms (SNPs) genotyping
      assay. Logistic regression was conducted to examine the associations between HLA
      G alleles and the risk of HIV transmission. The 14 bp insertion allele was more
      frequent in HIV exposed-uninfected (EU) infants than in infected infants, and was
      associated with reduced risk of both in utero (IU) and intrapartum (IP) HIV
      transmission, after adjusting for maternal cluster of differentiation 4 (CD4)
      cell count and plasma viral load. Maternal HLA-G 14 bp insertion genotype and HLA
      G concordance between mother and child were not associated with the risk of
      perinatal HIV transmission. The presence of the 14 bp insertion associates with
      protection toward IU and IP HIV infection in children from Zambia, suggesting
      that HLA-G could be involved in the vertical transmission of HIV. 

PMID- 24571475
TI  - The distribution of KIR-HLA functional blocks is different from north to south of
      Italy.
AB  - The killer cell immunoglobulin-like receptor (KIR)-human leukocyte antigen (HLA)
      interaction represents an example of genetic epistasis, where the concomitant
      presence of specific genes or alleles encoding receptor-ligand units is necessary
      for the activity of natural killer (NK) cells. Although KIR and HLA genes
      segregate independently, they co-evolved under environmental pressures to
      maintain particular KIR-HLA functional blocks for species survival. We
      investigated, in 270 Italian healthy individuals, the distribution of KIR and HLA
      polymorphisms in three climatic areas (from cold north to warm south), to verify
      their possible geographical stratification. We analyzed the presence of 13 KIR
      genes and genotyped KIR ligands belonging to HLA class I: HLA-C, HLA-B and HLA-A.
      We did not observe any genetic stratification for KIR genes and HLA-C ligands in
      Italy. By contrast, in a north-to-south direction, we found a decreasing trend
      for the HLA-A3 and HLA-A11 ligands (P = 0.012) and an increasing trend for the
      HLA-B ligands carrying the Bw4 epitope (P = 0.0003) and the Bw4 Ile80 epitope (P
      = 0.0005). The HLA-A and HLA-B KIR ligands were in negative linkage
      disequilibrium (correlation coefficient -0.1211), possibly as a consequence of
      their similar function in inhibiting NK cells. The distribution of the KIR-HLA
      functional blocks was different along Italy, as we observed a north-to-south
      ascending trend for KIR3DL1, when coupled with HLA-B Bw4 ligands (P = 0.0067) and
      with HLA-B Bw4 Ile80 (P = 0.0027), and a descending trend for KIR3DL2 when
      coupled with HLA-A3 and HLA-A11 ligands (P = 0.0044). Overall, people from South
      Italy preferentially use the KIR3DL1-HLA-B Bw4 functional unit, while those from
      the North Italy equally use both the KIR3DL2-HLA-A3/A11 and the KIR3DL1-HLA-B Bw4
      functional units to fight infections. Thus, only KIR3DL receptors, which exert
      the unique role of microbial sensors through the specific D0 domain, and their
      cognate HLA-A and HLA-B ligands are selectively pressured in Italy according to
      geographical north-to-south distribution. 

PMID- 24571477
TI  - G2848A and T-1237C polymorphisms of the TLR9 gene and susceptibility to
      inflammatory bowel disease in patients from southern Brazil.

PMID- 24571478
TI  - The novel allele, HLA-DPB1*04:01:15, is shared by a cord blood unit and
      corresponding maternal sample.
AB  - The novel allele HLA-DPB1*04:01:15 is different from DPB1*04:01:01:01 with one
      nucleotide at nt 351 (C > A) in exon 2. 

PMID- 24571479
TI  - Nomenclature for factors of the HLA system, update October 2013.

PMID- 24571476
TI  - Identification of 2127 new HLA class I alleles in potential stem cell donors from
      Germany, the United States and Poland.
AB  - We describe 2127 new human leukocyte antigen (HLA) class I alleles found in
      registered stem cell donors. These alleles represent 28.9% of the currently known
      class I alleles. Comparing new allele sequences to homologous sequences, we found
      68.1% nonsynonymous nucleotide substitutions, 28.9% silent mutations and 3.0%
      nonsense mutations. Many substitutions occurred at positions that have not been
      known to be polymorphic before. A large number of HLA alleles and nucleotide
      variations underline the extreme diversity of the HLA system. Strikingly, 156 new
      alleles were found not only multiple times, but also in carriers of various
      parentage, suggesting that some new alleles are not necessarily rare. Moreover,
      new alleles were found especially often in minority donors. This emphasizes the
      benefits of specifically recruiting such groups of individuals. 

PMID- 24571480
TI  - Nomenclature for factors of the HLA system, update November 2013.

PMID- 24571481
TI  - Nomenclature for factors of the HLA system, update December 2013.

PMID- 24571483
TI  - Effects of azilsartan compared to other angiotensin receptor blockers on left
      ventricular hypertrophy and the sympathetic nervous system in hemodialysis
      patients.
AB  - Hypertension is a major risk factor for cardiovascular and cerebrovascular
      events, and most patients with hypertension are administered antihypertensive
      drugs. However, not all patients achieve normal blood pressure levels. The new
      angiotensin receptor blocker azilsartan (Takeda Pharmaceutical Company Limited,
      Osaka, Japan) has been reported to have a strong hypotensive effect. Our study
      investigated the efficacy of azilsartan compared with other angiotensin receptor
      blockers. This study included 17 hypertensive patients on HD, who had been
      administered angiotensin receptor blockers, except for azilsartan, for more than
      6 months before enrolling, and after enrollment, they were switched to
      azilsartan. Blood tests, Holter electrocardiogram, ambulatory blood pressure
      monitoring, and echocardiography were performed at baseline and at the 6-month
      follow-up. The blood pressure from baseline to 6 months had significantly
      decreased (24-h systolic blood pressure from 150.9 +/- 16.2 mm Hg to 131.3 +/-
      21.7 mm Hg, P = 0.008), awakening time systolic blood pressure from 152.1 +/-
      16.9 mm Hg to 131.7 +/- 23.2 mm Hg, P = 0.01, sleep-time systolic blood pressure
      from 148.1 +/- 19.7 mm Hg to 130.0 +/- 20.1 mm Hg, P = 0.005). There was a
      significant reduction in serum noradrenaline levels as well as left ventricular
      mass index after switching to azilsartan (from 550.1 +/- 282.9 pg/mL, to 351.7 +/
      152.3 pg/mL, P = 0.002; from 117.0 +/- 26.4 g/m(2) to 111.3 +/- 23.9 g/m(2), P =
      0.01, respectively). Azilsartan had a significantly stronger hypotensive effect
      than other angiotensin receptor blockers. Thus, the switch to azilsartan might
      improve prognosis of hemodialysis patients. We suggest that the strong anti
      hypertensive effect of azilsartan originated from a combination of primary
      angiotensin receptor blocker class-effect and a stronger suppression of
      sympathetic nervous system.

PMID- 24571484
TI  - Diversity-oriented synthesis of ketoindoloquinoxalines and
      indolotriazoloquinoxalines from 1-(2-nitroaryl)-2-alkynylindoles.
AB  - A one-pot protocol for the diversity-oriented synthesis of two indole-based
      annulated polyheterocycles, ketoindoloquinoxalines and
      indolotriazoloquinoxalines, has been described. The salient features of the
      methodology involves either a metal/O2-catalyzed aminooxygenation or a [3 + 2]
      cycloaddition pathway. 

PMID- 24571482
TI  - The histone acetylranseferase hMOF acetylates Nrf2 and regulates anti-drug
      responses in human non-small cell lung cancer.
AB  - BACKGROUND AND PURPOSE: The histone acetyltransferase MOF is a member of the MYST
      family. In mammals, MOF plays critical roles by acetylating histone H4 at K16 and
      non-histone substrates such as p53. Here we have investigated the role of MOF in
      human lung cancer and possible new substrates of hMOF. EXPERIMENTAL APPROACH:
      Samples of human non-small cell lung cancer (NSCLC) were used to correlate MOF
      with clinicopathological parameters and NF-E2-related factor 2 (Nrf2) downstream
      genes. 293T-cells were used to study interactions between MOF and Nrf2, and
      acetylation of Nrf2 by MOF. Mouse embryonic fibroblast and A549 cells were
      utilized to assess involvement of MOF in antioxidative and anti-drug responses.
      A549 cells were used to analysis the role of MOF in anti-drug response in vitro
      and in vivo. KEY RESULTS: hMOF was overexpressed in human NSCLC tissues and was
      associated with large tumour size, advanced disease stage and metastasis, and
      with poor prognosis. hMOF levels were positively correlated with Nrf2-downstream
      genes. MOF/hMOF physically interacted with and acetylated Nrf2 at Lys(588) . MOF
      mediated acetylation increased nuclear retention of Nrf2 and transcription of its
      downstream genes. Importantly, MOF/hMOF was essential for anti-oxidative and anti
      drug responses in vitro and regulated tumour growth and drug resistance in vivo
      in an Nrf2-dependent manner. CONCLUSION AND IMPLICATIONS: hMOF was overexpressed
      in human NSCLC and was a predictor of poor survival. hMOF-mediated Nrf2
      acetylation and nuclear retention are essential for anti-oxidative and anti-drug
      responses. hMOF may provide a therapeutic target for the treatment of NSCLC.

PMID- 24571486
TI  - Cerebral Lipiodol embolism.

PMID- 24571485
TI  - Economic evaluation of a hypothetical screening assay for alloimmunization risk
      among transfused patients with sickle cell disease.
AB  - BACKGROUND: Prophylactic antigen-matching can reduce alloimmunization rates among
      chronically transfused patients with sickle cell disease (SCD), but this matching
      increases costs and may only benefit 30% of patients. We assessed the clinical
      and financial value of a potential assay for alloimmunization risk that would
      allow for targeted antigen-matching. STUDY DESIGN AND METHODS: A Markov-based
      model evaluated direct medical costs and alloimmunization events over 10 to 20
      years among transfused (simple or exchange) patients with SCD. Four matching
      strategies were evaluated: prospective matching (for all patients), history-based
      matching (only for patients with prior alloimmunization), perfectly informed
      matching (assay with 100% sensitivity, 100% specificity), and imperfectly
      informed matching (reduced accuracy). Under all matching protocols, matching
      included C, E, K, and any additional alloantibodies present. A hospital
      perspective was adopted, with costs (2012US$) and events discounted (3%).
      RESULTS: Perfectly informed antigen-matching using a $1000 assay is expected to
      save $82,334 per patient over 10 years, compared to prospective matching.
      Perfectly informed antigen-matching is more costly than history-based matching,
      but reduces alloimmunization events by 45.6% over 10 years. Averting each
      alloimmunization event using this strategy would cost an additional $10,934 per
      patient. Imperfectly informed antigen-matching using an assay with 75%
      specificity and 75% sensitivity is less costly than prospective matching, but
      increases alloimmunization events. Compared to history-based matching,
      imperfectly informed matching would decrease alloimmunization events by 32.61%,
      at an additional cost of $147,915 per patient over 10 years. Cost-effectiveness
      of informed antigen-matching is largely driven by assay specificity. CONCLUSIONS:
      A sufficiently specific assay to inform antigen-matching may be cost-effective in
      reducing alloimmunization among transfused patients with SCD.

PMID- 24571488
TI  - Identification of a novel HLA-DRB1*14 allele, HLA-DRB1*14:143, by sequence-based
      typing.
AB  - The novel HLA-DRB1*14:143 allele differs from DRB1*14:10 by two nucleotide
      substitutions at positions 344 and 345 of exon 2.

PMID- 24571487
TI  - Inhibition of mTORC1 induces loss of E-cadherin through AKT/GSK-3beta signaling
      mediated upregulation of E-cadherin repressor complexes in non-small cell lung
      cancer cells.
AB  - BACKGROUND: mTOR, which can form mTOR Complex 1 (mTORC1) or mTOR Complex 2
      (mTORC2) depending on its binding partners, is frequently deregulated in the
      pulmonary neoplastic conditions and interstitial lung diseases of the patients
      treated with rapalogs. In this study, we investigated the relationship between
      mTOR signaling and epithelial mesenchymal transition (EMT) by dissecting mTOR
      pathways. METHODS: Components of mTOR signaling pathway were silenced by shRNA in
      a panel of non-small cell lung cancer cell lines and protein expression of
      epithelial and mesenchymal markers were evaluated by immunoblotting and
      immunocytochemistry. mRNA level of the E-cadherin repressor complexes were
      evaluated by qRT-PCR. RESULTS: IGF-1 treatment decreased expression of the E
      cadherin and rapamycin increased its expression, suggesting hyperactivation of
      mTOR signaling relates to the loss of E-cadherin. Genetic ablation of rapamycin
      insensitive companion of mTOR (Rictor), a component of mTORC2, did not influence
      E-cadherin expression, whereas genetic ablation of regulatory-associated protein
      of mTOR (Raptor), a component of mTORC1, led to a decrease in E-cadherin
      expression at the mRNA level. Increased phosphorylation of AKT at Ser473 and GSK
      3beta at Ser9 were observed in the Raptor-silenced NSCLC cells. Of the E-cadherin
      repressor complexes tested, Snail, Zeb2, and Twist1 mRNAs were elevated in raptor
      silenced A549 cells, and Zeb2 and Twist1 mRNAs were elevated in Raptor-silenced
      H2009 cells. These findings were recapitulated by treatment with the GSK-3beta
      inhibitor, LiCl. Raptor knockdown A549 cells showed increased expression of N
      cadherin and vimentin with mesenchymal phenotypic changes. CONCLUSIONS: In
      conclusion, selective inhibition of mTORC1 leads to hyperactivation of the
      AKT/GSK-3beta pathway, inducing E-cadherin repressor complexes and EMT. These
      findings imply the existence of a feedback inhibition loop of mTORC1 onto mTORC2
      that plays a role in the homeostasis of E-cadherin expression and EMT, requiring
      caution in the clinical use of rapalog and selective mTORC1 inhibitors.

PMID- 24571490
TI  - Influence of dialysis duration on the outcome of living kidney transplantation.
AB  - Previous studies have reported negative impacts of long-term dialysis on kidney
      transplantation (KTx) outcomes. However, advances in surgical techniques,
      immunosuppressive therapies, and post-transplant monitoring have led to an
      impressive increase in patient and allograft survival. Thus, the number of KTx
      among patients on long-term dialysis is increasing. We evaluated the influence of
      dialysis duration on the outcome of living donor KTx. Between January 2000 and
      October 2011, we performed 1098 first KTx from living donors in adults (>18
      years). We divided the patients into six groups, A group: pre-emptive kidney
      transplantation, B group: <24 months duration of dialysis, C group: 25-60 months
      duration, D group: 61-120 months duration, E group: 121-240 months duration, and
      F group: >= 241 months duration. The 5-year patient survival rates were 95.7,
      98.8, 99.0, 99.0, 97.3, and 100% in groups A-F, respectively. The 5-year graft
      survival rates were 91.3, 95.6, 94.2, 96.3, 90.7, and 100% in groups A-F,
      respectively. No significant differences were observed in patient or graft
      survival among the six groups. Longer dialysis duration was correlated with lower
      rates of preoperative hypertension and diabetes mellitus. Survivors of long-term
      dialysis tended to be in good compliance with self-management. If recipients of
      living KTx have few complications, good prognoses are expectable even if dialysis
      periods are very long.

PMID- 24571489
TI  - Using viruses as nanomedicines.
AB  - The field of nanomedicine involves the design and fabrication of novel
      nanocarriers for the intracellular delivery of therapeutic cargo or for use in
      molecular diagnostics. Although traditionally recognized for their ability to
      invade and infect host cells, viruses and bacteriophages have been engineered
      over the past decade as highly promising molecular platforms for the targeted
      delivery and treatment of many human diseases. Inherently biodegradable, the
      outer capsids of viruses are composed entirely of protein building blocks, which
      can be genetically or chemically engineered with molecular imaging reagents,
      targeting ligands and therapeutic molecules. While there are several examples of
      viruses as in vitro molecular cargo carriers, their potential for applications in
      nanomedicine has only recently emerged. Here we highlight recent developments
      towards the design and engineering of viruses for the treatment of cancer,
      bacterial infections and immune system-related diseases.

PMID- 24571491
TI  - Identification and fine mapping of quantitative trait loci for seed vigor in
      germination and seedling establishment in rice.
AB  - Seed vigor is an index of seed quality that is used to describe the rapid and
      uniform germination and the establishment of strong seedlings in any
      environmental conditions. Strong seed vigor in low-temperature germination
      conditions is particularly important in direct-sowing rice production systems.
      However, seed vigor has not been selected as an important breeding trait in
      traditional breeding programs due to its quantitative inherence. In this study,
      we identified and mapped eight quantitative trait loci (QTLs) for seed vigor by
      using a recombinant inbred population from a cross between rice (Oryza sativa L.
      ssp. indica) cultivars ZS97 and MH63. Conditional QTL analysis identified qSV-1,
      qSV-5b, qSV-6a, qSV-6b, and qSV-11 influenced seedling establishment and that qSV
      5a, qSV-5c, and qSV-8 influenced only germination. Of these, qSV-1, qSV-5b, qSV
      6a, qSV-6b, and qSV-8 were low-temperature-specific QTLs. Two major-effective
      QTLs, qSV-1, and qSV-5c were narrowed down to 1.13-Mbp and 400-kbp genomic
      regions, respectively. The results provide tightly linked DNA markers for the
      marker-assistant pyramiding of multiple positive alleles for increased seed vigor
      in both normal and low-temperature germination environments. 

PMID- 24571493
TI  - Empirical multidimensional space for scoring peptide spectrum matches in shotgun
      proteomics.
AB  - Data-dependent tandem mass spectrometry (MS/MS) is one of the main techniques for
      protein identification in shotgun proteomics. In a typical LC-MS/MS workflow,
      peptide product ion mass spectra (MS/MS spectra) are compared with those derived
      theoretically from a protein sequence database. Scoring of these matches results
      in peptide identifications. A set of peptide identifications is characterized by
      false discovery rate (FDR), which determines the fraction of false
      identifications in the set. The total number of peptides targeted for
      fragmentation is in the range of 10,000 to 20,000 for a several-hour LC-MS/MS
      run. Typically, <50% of these MS/MS spectra result in peptide-spectrum matches
      (PSMs). A small fraction of PSMs pass the preset FDR level (commonly 1%) giving a
      list of identified proteins, yet a large number of correct PSMs corresponding to
      the peptides originally present in the sample are left behind in the "grey area"
      below the identity threshold. Following the numerous efforts to recover these
      correct PSMs, here we investigate the utility of a scoring scheme based on the
      multiple PSM descriptors available from the experimental data. These descriptors
      include retention time, deviation between experimental and theoretical mass,
      number of missed cleavages upon in-solution protein digestion, precursor ion
      fraction (PIF), PSM count per sequence, potential modifications, median fragment
      mass error, (13)C isotope mass difference, charge states, and number of PSMs per
      protein. The proposed scheme utilizes a set of metrics obtained for the
      corresponding distributions of each of the descriptors. We found that the
      proposed PSM scoring algorithm differentiates equally or more efficiently between
      correct and incorrect identifications compared with existing postsearch
      validation approaches.

PMID- 24571492
TI  - Development of a Suzuki cross-coupling reaction between 2-azidoarylboronic
      pinacolate esters and vinyl triflates to enable the synthesis of [2,3]-fused
      indole heterocycles.
AB  - The scope and limitations of a Suzuki reaction between 2-azidoarylboronic acid
      pinacolate esters and vinyl triflates are reported. This cross-coupling reaction
      enables the regioselective synthesis of indoles after a subsequent Rh(II)2
      catalyzed sp(2)-C-H bond amination reaction. 

PMID- 24571494
TI  - Effectiveness of an intervention to improve day centre services for people with
      psychiatric disabilities.
AB  - BACKGROUND/AIM: Day centres for people with psychiatric disabilities need to be
      evaluated for effectiveness in order to provide the best possible support. This
      study aimed at investigating the effectiveness of a tailor-made intervention to
      improve day centre services for people with psychiatric disabilities. METHODS:
      The intervention was devised to bridge identified gaps in the services and lasted
      for 14 months. Eight centres were allotted to the intervention (55 attendees) or
      comparison condition (51 attendees). Fidelity to the intervention and major
      events in the day centres were assessed. The outcomes were degree of
      meaningfulness found in the day centre occupations, satisfaction with the
      rehabilitation received, satisfaction with everyday occupations and quality of
      life. RESULTS: The fidelity to the intervention was good, but more positive
      events, such as new occupational opportunities, had taken place in the comparison
      units. No differences were identified between the intervention and the comparison
      group regarding changes from baseline to the 14-month follow-up in perceived
      meaningfulness among day centre occupations, satisfaction with everyday
      occupations or quality of life. CONCLUSIONS: The intervention seemed ineffective,
      but the positive events in the comparison group resembled the measures included
      in the tailor-made interventions. This first intervention study in the day centre
      context has hopefully helped to generate hypotheses and methods for future
      research.

PMID- 24571495
TI  - Iranian nurses' perspectives on factors influencing medication errors.
AB  - BACKGROUND: Medical errors are one of the major threats for patient safety in all
      countries. Medication errors are common medical mistakes that can lead to serious
      consequences and even death of patients. AIM: The aim of this study was to
      explore nurses' perspectives of factors influencing medication errors. METHODS:
      This qualitative study based on content analysis included 20 nurses (n = 20) with
      at least 2 years of clinical experience working in a large teaching hospital. The
      nurses were selected using purposeful sampling. The data were collected using
      semi-structured interviews and analysed using deductive content analysis approach
      based on Reason's human error model. Rigor of the data was confirmed by external
      and member check. RESULTS: Two themes were identified by the participants: (1)
      the individual approach including personal and psychological characteristics of
      nurses, patient medical history and physicians' orders errors; and (2) the
      cultural and organizational approach including workplace conditions, learning
      process, risk management strategies, nurses' pharmacological knowledge,
      inevitable nursing errors and medication error complications. LIMITATIONS:
      Concern about the potential consequences related to reporting of the medication
      errors was the major limitation of this study. Participants' concerns were
      handled by keeping their identity confidential and anonymous. CONCLUSION: Results
      show the importance of planning comprehensive educational programmes and
      providing constructive feedback in a favourable learning climate. IMPLICATIONS
      FOR NURSING AND HEALTH POLICY: Findings of this study can be beneficial to
      managers for nurturing a transparent organizational culture, whereby staff
      members freely discuss their errors in patient care and seek advice for problem
      solving.

PMID- 24571496
TI  - Motor dual-task Timed Up & Go test better identifies prefrailty individuals than
      single-task Timed Up & Go test.
AB  - AIM: The present study investigated whether dual-task Timed Up & Go tests (TUG)
      could identify prefrail individuals more sensitively than the single-task TUG
      (TUGsingle ) in community-dwelling middle-aged and older adults. METHODS: This
      cross-sectional study recruited adults aged 50 years and older who actively
      participated in local community programs. Time taken to complete single-task TUG
      and dual-task TUG, carrying a cup of water (TUGmanual ) or carrying out serial-3
      subtraction (TUGcognitive ) while executing TUG, was measured. Prefrailty status
      was defined based on Fried's phenotypic definition. RESULTS: Of the 65
      participants (mean age 71.5+/-8.1 years), 33.3% of the 12 middle-aged (50-64
      years) and 62.3% of the 53 older (>=65 years) adults were prefrail, mainly as a
      result of weak grip strength. The receiver operating characteristic curve
      analyses for differentiating prefrailty from non-frailty showed that the area
      under the curve (AUC) for TUGmanual (0.73, 95% CI 0.60-0.86) was better than that
      for TUGsingle (0.67, 95% CI 0.54-0.80), whereas the AUC value was not significant
      for TUGcognitive (0.60, 95% CI 0.46-0.74). The optimal cut-off points for
      detecting prefrailty using TUGsingle , TUGmanual and TUGcognitive were 7.7 s
      (sensitivity 68%), 8.2 s (sensitivity 83%), and 14.3 s (sensitivity 29%),
      respectively. After adjusting for age, logistic regression analyses showed that
      individuals with TUGmanual 8.2 s or slower were 7.2-fold more likely to have
      prefrailty than those with TUGmanual faster than 8.2 s. CONCLUSION: TUGmanual is
      more valid and sensitive than TUGsingle in identifying prefrail individuals. The
      TUGmanual thus could serve as a screening tool for early detection of individuals
      with prefrailty in community-dwelling middle-aged and older adults.

PMID- 24571497
TI  - An algorithmic programming approach for back pain symptoms in failed back surgery
      syndrome using spinal cord stimulation with a multicolumn surgically implanted
      epidural lead: a multicenter international prospective study.
AB  - INTRODUCTION: Many studies have demonstrated the efficacy and the
      medical/economic value of epidural spinal cord stimulation for the treatment of
      "failed back surgery syndrome" (FBSS). However, the back pain component of FBSS
      has been recalcitrant. Recent clinical trials have suggested that multicolumn
      surgically implanted leads combined with enhanced programming capabilities in the
      newer implantable pulse generators demonstrate the ability to treat the back pain
      component of FBSS. The objective of our present international multicentre study
      is to prospectively evaluate these findings in a larger population. METHODS: We
      conducted a prospective, nonrandomized, observational study on 76 patients with
      refractory FBSS, consecutively implanted with multicolumn spinal cord stimulation
      (SCS) between 2008 and 2011 in three neurosurgical pain management centers
      (Poitiers, France; Montreal, Canada; and Regina, Canada). The primary objective
      of this study was to prospectively analyze the effect of multicolumn lead
      programming on paresthesia coverage for the back pain region in these patients.
      The secondary objective was to assess the analgesic efficacy of this technique on
      the global and back pain components. RESULTS: Paresthesia could be induced in the
      lower extremities in the majority of patients with at least one of the
      configurations tested. Bilateral low back paresthesia was induced in 53.5% of
      patients, while unilateral low back paresthesia was induced in 78.9% of patients.
      Multicolumn configurations were statistically more effective than monocolumn
      configurations for all anatomic regions studied. At 6 months, 75.4% of patients
      receiving multicolumn stimulation (n = 57) obtained at least a 30% improvement of
      the back pain VAS score, while 42.1% of patients obtained at least a 50%
      improvement of the back pain VAS score. CONCLUSION: This study confirms the
      hypothesis that multicolumn SCS should be considered as an important tool in the
      treatment of radicular and axial pain in FBSS patients. The efficacy of this
      modality is based on a rigorous patient selection process, access to new
      generation lead technologies, but most importantly an algorithmic programming
      approach for optimal stimulation and electrical field shaping. With over 40
      million potential programming combinations associated with 16 contact leads to
      achieve paresthesia coverage, optimal stimulation is often missed as either the
      patient or the clinician become exhausted or overwhelmed during the course of
      therapy programming and optimization session.

PMID- 24571498
TI  - Determination of carbohydrate-deficient transferrin in a Han Chinese population.
AB  - BACKGROUND: Carbohydrate-deficient transferrin (CDT) is a widely used alcohol
      biomarker. Because of the high prevalence of chronic alcohol abuse in many
      countries, CDT plays an important role in the areas of traffic, clinical, and
      forensic medicine. However, CDT levels have not been determined in the Han
      Chinese population. Therefore, we investigated the frequency of genetic
      transferrin variants and the relationship between CDT levels and alcohol
      consumption in this population. From this data, we established a CDT cut-off for
      Han Chinese and evaluated the analytical performance of the CDT capillary zone
      electrophoresis system. RESULTS: The prevalence of transferrin variants was
      4.14%. The mean CDT level of the reference group was 0.73%. We recommended CDT
      level >1.5% as cut off standard of alcohol intake to ensuring the specificity was
      best. The CDT test total precision for 0.5%, 0.7%, and 1.55% was 14.4%, 11.5%,
      and 7.2%, respectively. The data showed good linearity in the studied range of
      0.6% to 8.2%. CONCLUSIONS: These results demonstrate that CDT is a useful marker
      to detect heavy daily alcohol consumption. We proposed and evaluated the first
      CDT cut-off for the Han Chinese population, and we showed that the CDT capillary
      zone electrophoresis system is a reliable analytic method.

PMID- 24571500
TI  - Case of peritoneal dialysis-related peritonitis and associated tunnel infection
      due to group G streptococcus.

PMID- 24571501
TI  - Overcoming barriers to implementing new technologies in the dental practice.

PMID- 24571502
TI  - Advancing wellness in the dental office through use of screening and diagnostic
      technology.
AB  - Implementing an oral health/systemic health wellness plan for patients can be an
      important part of a dental practice's proactive approach to healthcare that
      emphasizes early detection and treatment of disease. As an adjunct to clinical
      observations, medical history, and patient information gathered and assessed by
      the practitioner, utilization of screening and diagnostic technology, including
      oral cancer screening devices, salivary diagnostic tests, and caries detection
      devices, can aid in the early detection of disease. These tests, which are
      usually billable, can aid in providing timely, effectual wellness services to
      patients by enabling practitioners to supply these services more effectively and
      at an early stage to the benefit of the patient's overall health. 

PMID- 24571499
TI  - Heteromers of MU-delta opioid receptors: new pharmacology and novel therapeutic
      possibilities.
AB  - Several studies suggest that heteromerization between MU (MOP) and delta (DOP)
      opioid receptors modulates the signalling properties of the individual receptors.
      For example, whereas activation of MOP receptors by an agonist induces G protein
      mediated signalling, the same agonist induces beta-arrestin-mediated signalling
      in the context of the MOP-DOP receptor heteromer. Moreover, heteromer-mediated
      signalling is allosterically modulated by a combination of MOP and DOP receptor
      ligands. This has implications in analgesia given that morphine-induced
      antinociception can be potentiated by DOP receptor ligands. Recently reagents
      selectively targeting the MOP-DOP receptor heteromer such as bivalent ligands,
      antibodies or membrane permeable peptides have been generated; these reagents are
      enabling studies to elucidate the contribution of endogenously expressed
      heteromers to analgesia as well as to the development of side-effects associated
      with chronic opioid use. Recent advances in drug screening technology have led to
      the identification of a MOP-DOP receptor heteromer-biased agonist that activates
      both G protein-mediated and beta-arrestin-mediated signalling. Moreover, this
      heteromer-biased agonist exhibits potent antinociceptive activity but with
      reduced side-effects, suggesting that ligands targeting the MOP-DOP receptor
      heteromer form a basis for the development of novel therapeutics for the
      treatment of pain. In this review, we summarize findings regarding the biological
      and functional characteristics of the MOP-DOP receptor heteromer and the in vitro
      and in vivo properties of heteromer-selective ligands. LINKED ARTICLES: This
      article is part of a themed section on Opioids: New Pathways to Functional
      Selectivity. To view the other articles in this section visit
      http://dx.doi.org/10.1111/bph.2015.172.issue-2.

PMID- 24571503
TI  - Assessing image-guided implant surgery in today's clinical practice.
AB  - As implant dentistry has progressed, greater emphasis has been placed on natural
      looking tooth replacement, minimally invasive techniques, and better cost
      efficiencies, with implant positioning being guided by the desired prosthetic
      outcome. Image-guided surgery is a technique that merges preoperative diagnostic
      imaging with computer-based planning tools to facilitate surgical and restorative
      plans and procedures. This article discusses the intricacies of guided implant
      surgery, including 3-dimensional presurgical planning and the challenges of
      maintaining guide stability during surgical execution. 

PMID- 24571504
TI  - Diode laser soft-tissue surgery: advancements aimed at consistent cutting,
      improved clinical outcomes.
AB  - Laser dentistry and soft-tissue surgery, in particular, have become widely
      adopted in recent years. Significant cost reductions for dental lasers and the
      increasing popularity of CADCAM, among other factors, have contributed to a
      substantial increase in the installed base of dental lasers, especially soft
      tissue lasers. New development in soft-tissue surgery, based on the modern
      understanding of laser-tissue interactions and contact soft-tissue surgery
      mechanisms, will bring a higher quality and consistency level to laser soft
      tissue surgery. Recently introduced diode-laser technology enables enhanced
      control of side effects that result from tissue overheating and may improve soft
      tissue surgical outcomes. 

PMID- 24571505
TI  - CAD/CAM technology and esthetic dentistry: a case report.
AB  - Advances in dental materials as well as in computer technology have made CADCAM
      fabricated restorations not just possible in dentistry but plentiful. When using
      CADCAM systems, operators can fabricate restorations from several materials,
      including ceramics, metal alloys, and various composites. This case report
      describes the replacement of a porcelain-layered zirconia-based (coping) crown on
      a left lower cuspid that presented with a veneering ceramic chipping on a lithium
      disilicate CADCAM-fabricated crown. It demonstrates how all-ceramic systems offer
      a promising alternative in the restoration of anterior teeth. 

PMID- 24571506
TI  - The Photoshop Smile Design technique (part 1): digital dental photography.
AB  - The proliferation of digital photography and imaging devices is enhancing
      clinicians' ability to visually document patients' intraoral conditions. By
      understanding the elements of esthetics and learning how to incorporate
      technology applications into clinical dentistry, clinicians can predictably plan
      smile design and communicate anticipated results to patients and ceramists alike.
      This article discusses camera, lens, and flash selection and setup, and how to
      execute specific types of images using the Adobe Photoshop Smile Design (PSD)
      technique. 

PMID- 24571507
TI  - Digital dentistry: a new era of patient care.

PMID- 24571508
TI  - Color- and morphology-controlled self-assembly of new electron-donor-substituted
      aggregation-induced emission compounds.
AB  - Four electron-donor-substituted aggregation-induced emission (AIE) compounds,
      N,N'-bis(4-methoxylsalicylidene)-p-phenylenediamine (BSPD-OMe), N,N'-bis(4
      methylsalicylidene)-p-phenylenediamine (BSPD-Me), N,N'-bis(salicylidene)-p
      phenylenediamine (BSPD), and N,N'-bis(4-hydroxylsalicylidene)-p-phenylenediamine
      (BSPD-OH), are designed and synthesized. They are all found to exhibit controlled
      self-assembly behaviors and good thermal properties. By changing the terminal
      electron-donor groups, they are controlled to self-assemble into three emission
      colors (green, yellow, and orange) and four morphologies (microblocks,
      microparticles, microrods, and nanowires) in THF/water mixtures. Their self
      assembled structures were investigated with scanning electron microscopy (SEM),
      fluorescent microscopy images, transmission electron microscopy (TEM), and powder
      X-ray diffraction (PXRD) techniques. In addition, the emission colors of BSPD-OH
      can be successfully controlled to three colors (green -> yellow -> orange)
      through simply changing the water fraction (fw). Their thermal gravimetric
      analysis (TGA) results indicate that their thermal decomposition temperatures
      (Td, corresponding to 5% weight loss) range from 282 to 319  degrees C. Their
      differential scanning calorimetry (DSC) data show that BSPD-OH bears a glass
      transition temperature (Tg) of 118  degrees C. The good Td and Tg values will
      ensure them to be luminogens for organic light-emitting diodes (OLEDs). The
      theoretical calculations and single-crystal X-ray diffraction (XRD) analysis of
      BSPD-OMe and BSPD suggest that the stronger electron donor substituent can twist
      the molecular conformation, decrease the degree of pi conjugation, increase the
      energy gap, and then induce the emission colors' blue shift and morphology
      variation. The results are meaningful in controlling the emission colors and self
      assembly shapes of these derivatives, and they also provide a novel but facile
      way to get color-tunable AIE luminogens for OLEDs. 

PMID- 24571510
TI  - Artificial organ technologies around the world.

PMID- 24571509
TI  - A simple alopecia scoring system for use in colony management of laboratory
      housed primates.
AB  - BACKGROUND: Alopecia in captive primates continues to receive attention from
      animal care personnel and regulatory agencies. However, a method that enables
      personnel to reliably score alopecia over time and under various conditions has
      proven difficult to achieve. METHODS: The scoring system developed by the
      behavioral and veterinary staffs at the Washington National Primate Research
      Center (WaNPRC) uses the rule of 9s to estimate the percentage of the body
      affected with alopecia (severity) and how the alopecia presents itself (pattern).
      Training and scoring can conveniently be managed using photographic images, cage
      side observations, and/or physical examinations. RESULTS: Personnel with varying
      degrees of experience were quickly trained with reliability scores ranging from
      0.82 to 0.96 for severity and 0.82 to 0.89 for pattern using Cohen's kappa.
      CONCLUSIONS: This system allows for reliable and consistent scoring across
      species, sex, age, housing condition, seasons, clinical or behavioral treatments,
      and level of personnel experience.

PMID- 24571512
TI  - Successful insertion of a tunneled-cuffed catheter in a patient with multiple
      stenoses of the central vein.

PMID- 24571511
TI  - The effects of recombinant human bone morphogenetic protein-2-loaded tricalcium
      phosphate microsphere-hydrogel composite on the osseointegration of dental
      implants in minipigs.
AB  - Bone formation in tooth defect areas and the osseointegration of dental implants
      are very important for successful dental implant surgery. The aim of the present
      study was to assess the strengthening effect of a beta-TCP microsphere-hydrogel
      composite containing recombinant human bone morphogenetic protein-2 (rhBMP-2) on
      bone healing and implant osseointegration. The molars and premolars on the left
      and right sides of the maxilla were extracted from six male minipigs, and dental
      implants were placed using either the beta-TCP microsphere-hydrogel carrier alone
      or the carrier loaded with rhBMP-2 (500 MUg). The animals were kept alive for a
      further 8 weeks. The molars and premolars from the left and the right sides of
      the mandibles of another six minipigs were extracted, and the animals were kept
      alive for 4 weeks. Two 5-mm-diameter bone defects were then made on both sides of
      the mandible. The defects were filled with saline, beta-TCP microsphere-hydrogel
      carrier, or the carrier loaded with rhBMP-2 (300 MUg), and dental implant
      fixtures were inserted. The animals were kept alive for a further 4 weeks. Bone
      formation was examined using plane radiographs, micro-CT, and the histology of
      undecalcified specimens. The group treated with the rhBMP-2-loaded carrier
      composite showed a significantly higher percentage bone volume and a greater
      trabecular thickness for the newly formed bone in the tooth defect areas when
      compared to the group treated with the carrier alone. The rhBMP-2 group had a
      significantly higher osseointegration, a larger percentage bone volume, greater
      trabecular thickness in the newly formed bone in tooth defect areas, a larger
      newly formed bone fraction in the fixture pitch, and a greater number of newly
      formed trabecular bones when compared to the other groups. We confirmed that the
      rhBMP-2-loaded carrier composite promotes new bone formation after tooth
      extraction and strengthens osseointegration of dental fixtures by improving the
      degree of osseointegration around the dental implant fixture. 

PMID- 24571514
TI  - Implantation of scaffold-free engineered cartilage constructs in a rabbit model
      for chondral resurfacing.
AB  - Joint resurfacing techniques offer an attractive treatment for damaged or
      diseased cartilage, as this tissue characteristically displays a limited capacity
      for self-repair. While tissue-engineered cartilage constructs have shown efficacy
      in repairing focal cartilage defects in animal models, a substantial number of
      cells are required to generate sufficient quantities of tissue for the repair of
      larger defects. In a previous study, we developed a novel approach to generate
      large, scaffold-free cartilaginous constructs from a small number of donor cells
      (20 000 cells to generate a 3-cm(2) tissue construct). As comparable thicknesses
      to native cartilage could be achieved, the purpose of the present study was to
      assess the ability of these constructs to survive implantation as well as their
      potential for the repair of critical-sized chondral defects in a rabbit model.
      Evaluated up to 6 months post-implantation, allogenic constructs survived weight
      bearing without a loss of implant fixation. Implanted constructs appeared to
      integrate near-seamlessly with the surrounding native cartilage and also to
      extensively remodel with increasing time in vivo. By 6 months post-implantation,
      constructs appeared to adopt both a stratified (zonal) appearance and a
      biochemical composition similar to native articular cartilage. In addition,
      constructs that expressed superficial zone markers displayed higher histological
      scores, suggesting that transcriptional prescreening of constructs prior to
      implantation may serve as an approach to achieve superior and/or more consistent
      reparative outcomes. As the results of this initial animal study were
      encouraging, future studies will be directed toward the repair of chondral
      defects in more mechanically demanding anatomical locations. 

PMID- 24571515
TI  - Using memories to motivate future behaviour: an experimental exercise
      intervention.
AB  - This study tested a novel memory-based experimental intervention to increase
      exercise activity. Undergraduate students completed a two-part online survey
      ostensibly regarding college activity choices. At Time 1, they completed
      questionnaires that included assessments of exercise-related attitudes,
      motivation and self-reported behaviours. Next, they described a memory of a
      positive or negative experience that would increase their motivation to exercise;
      students in a control condition did not receive a memory prompt. Finally, they
      rated their intentions to exercise in the future. Eight days following Time 1,
      students received a Time 2 survey that included an assessment of their self
      reported exercise during the prior week. Students in the positive memory
      condition reported higher levels of subsequent exercise than those in the control
      condition; students in the negative memory condition reported intermediate levels
      of exercise. Activating a positive motivational memory had a significant effect
      on students' self-reported exercise activity even after controlling for prior
      attitudes, motivation and exercise activity. 

PMID- 24571517
TI  - Molecular dynamics simulation of C-C bond scission in polyethylene and linear
      alkanes: effects of the condensed phase.
AB  - The reaction of C-C bond scission in polyethylene chains of various lengths was
      studied using molecular dynamics under the conditions of vacuum and condensed
      phase (polymer melt). A method of assigning meaningful rate constant values to
      condensed-phase bond scission reactions based on a kinetic mechanism accounting
      for dissociation, reverse recombination, and diffusional separation of fragments
      was developed. The developed method accounts for such condensed-phase phenomena
      as cage effects and diffusion of the decay products away from the reaction site.
      The results of C-C scission simulations indicate that per-bond rate constants
      decrease by an order of magnitude as the density of the system increases from
      vacuum to the normal density of a polyethylene melt. Additional calculations were
      performed to study the dependence of the rate constant on the length of the
      polymer chain under the conditions of the condensed phase. The calculations
      demonstrate that the rate constant is independent of the degree of polymerization
      if polyethylene samples of different lengths are kept at the same pressure.
      However, if instead molecular systems of different polyethylene chain lengths
      decompose under the conditions of the same density, shorter chains result in
      higher pressures and lower rate constants. The observed effect is attributed to a
      higher degree of molecular crowding (lower fraction of free intermolecular space
      available for molecular motion) in the case of shorter molecules. 

PMID- 24571516
TI  - New Zealand nurses' views on preceptoring international nurses.
AB  - BACKGROUND: New Zealand encourages internationally educated nurses to seek
      registration in New Zealand to reduce local nursing shortages. Internationally
      educated nurses must meet requirements of the Health Practitioners Competency
      Assurance Act 2003, and demonstrate competency to practise through a clinical
      competency assessment programme. AIM: The purpose was to establish whether
      preceptors believe they are adequately prepared to assess nurses for whom English
      is a second language, and to determine the support and recognition received in
      the role. METHODS: Preceptor training, workload, understanding of ethical and
      legal accountability, and perceived organizational values, support and attitudes
      were evaluated via an anonymous internet survey. RESULTS: Some preceptors do not
      meet Nursing Council of New Zealand standards and some work environments require
      nurses to preceptor international nurses. Many nurses believe the role is not
      valued despite the high workload requirements. Training increased preceptor
      confidence and preparedness for clinical assessment but additional education is
      required to understand ethical and legal accountability within the role. Many
      preceptors indicated they felt pressured into recording assessments they were
      uncomfortable with. DISCUSSION: Enhancing preceptorship acceptance could be
      achieved through institutional recognition of the role's value via workload
      consideration, institutional recognition or financial means. Increased
      preceptorship training, particularly around ethical and legal issues, would
      encourage preceptor confidence. CONCLUSIONS: Organizations must find ways of
      meeting these challenges while recognizing they are responsible for the work
      environment of both preceptors and internationally registered nurses for whom
      English is a second language. A register of preceptors could provide a platform
      for audit and quality assurance principles, ensuring adequate education and
      preparation of preceptors. IMPLICATIONS FOR NURSING AND HEALTH POLICY: Effective
      preceptorship requires training, recognition and support. Successful integration
      of international nurses depends on organizational recognition and implementation
      of these factors.

PMID- 24571518
TI  - A hybrid method to estimate the minimum effective dose for monotone and non
      monotone dose-response relationships.
AB  - This article proposes a new multiple-testing approach for estimation of the
      minimum effective dose allowing for non-monotonous dose-response shapes. The
      presented approach combines the advantages of two commonly used methods. It is
      shown that the new approach controls the error rate of underestimating the true
      minimum effective dose. Monte Carlo simulations indicate that the proposed method
      outperforms alternative methods in many cases and is only marginally worse in the
      remaining situations. 

PMID- 24571519
TI  - Deep functional redundancy between FAMA and FOUR LIPS in stomatal development.
AB  - Functional redundancy arises between gene paralogs as well as non-homologous
      genes that play a common role at a shared node. The bHLH transcription factor
      FAMA, along with the paralogous MYB genes, FOUR LIPS (FLP) and MYB88 all ensure
      that Arabidopsis stomata contain just two guard cells (GCs) by enforcing a single
      symmetric precursor cell division before stomatal maturity. Consistent with this
      function, FLP and FAMA exhibit the same expression pattern in which both
      translational GFP fusions emit fluorescence just before and after symmetric
      division; however, FAMA but not FLP is required to confer GC fate. Strikingly,
      swapping the genes and promoters of the FLP and FAMA genes results in the
      reciprocal complementation of respective loss-of-function mutants. Thus, an FLP
      transgene can restore GC fate to a fama mutant background. FAMA, FLP and the FLP
      paralog MYB88 were previously shown to influence higher order functions in
      stomatal development, including maintaining and stabilizing stomatal fate. Here
      we show that these overlapping functions are likely to also involve interactions
      between FLP and FAMA with the RETINOBLASTOMA-RELATED (RBR) protein. 

PMID- 24571522
TI  - "Palliative hemodialysis" in the context of end-of-life care for dialysis
      patients.

PMID- 24571521
TI  - Associations between pain drawing and psychological characteristics of different
      body region pains.
AB  - BACKGROUND: Pain drawings have frequently been used for documentation of pain and
      a convenient diagnosis tool. Pain drawings were found to be associated with
      psychological states in chronic patients with low back pain. Few researchers have
      investigated pain drawings except in low back pain. The aim of this study was to
      investigate the pain, pain drawings, psychological characteristics, and pain
      interference in the head, neck-shoulder (NS), and low-back/lower-limb (LB-LL)
      regions among patients with chronic pain. METHODS: We included a total of 291
      patients with new chronic pain (headache, 62; NS pain, 87; LB-LL pain, 142). The
      pain drawings and scores of 10-cm Visual Analogue Scale (VAS), Hospital Anxiety
      and Depression Scale (HADS), Pain Catastrophizing Scale (PCS), Short-Form McGill
      Pain Questionnaire (SF-MPQ), and Pain Disability Assessment Scale (PDAS) were
      extracted from medical records. A subset of 60 pain drawings was scored by senior
      and junior evaluators to assess inter-rater agreement. We investigated the
      correlation between pain drawings and VAS, HADS, PCS, SF-MPQ, and PDAS in each
      body region group at the initial visit. Moreover, almost all patients received
      nonsurgical treatment as a follow-up and were investigated using VAS after
      treatment. RESULTS: The reliability of pain drawings was substantial with an
      interevaluator reliability in headache, NS, and LB-LL pain. Nonorganic pain
      drawings were associated with psychological disturbances in NS and LB-LL pain,
      but not headache. Poor outcomes were associated with nonorganic drawings in LB-LL
      pain, but not in the case of headache or NS pain. CONCLUSIONS: Our results
      suggest that the characteristics of patients with nonorganic drawings differ
      according to body regions.

PMID- 24571520
TI  - Combining techniques for screening and evaluating interaction terms on high
      dimensional time-to-event data.
AB  - BACKGROUND: Molecular data, e.g. arising from microarray technology, is often
      used for predicting survival probabilities of patients. For multivariate risk
      prediction models on such high-dimensional data, there are established techniques
      that combine parameter estimation and variable selection. One big challenge is to
      incorporate interactions into such prediction models. In this feasibility study,
      we present building blocks for evaluating and incorporating interactions terms in
      high-dimensional time-to-event settings, especially for settings in which it is
      computationally too expensive to check all possible interactions. RESULTS: We use
      a boosting technique for estimation of effects and the following building blocks
      for pre-selecting interactions: (1) resampling, (2) random forests and (3)
      orthogonalization as a data pre-processing step. In a simulation study, the
      strategy that uses all building blocks is able to detect true main effects and
      interactions with high sensitivity in different kinds of scenarios. The main
      challenge are interactions composed of variables that do not represent main
      effects, but our findings are also promising in this regard. Results on real
      world data illustrate that effect sizes of interactions frequently may not be
      large enough to improve prediction performance, even though the interactions are
      potentially of biological relevance. CONCLUSION: Screening interactions through
      random forests is feasible and useful, when one is interested in finding relevant
      two-way interactions. The other building blocks also contribute considerably to
      an enhanced pre-selection of interactions. We determined the limits of
      interaction detection in terms of necessary effect sizes. Our study emphasizes
      the importance of making full use of existing methods in addition to establishing
      new ones.

PMID- 24571523
TI  - Evidence-based dentistry as it relates to dental materials.
AB  - Evidence-based dentistry (EBD) is reviewed in depth to underscore the limitations
      for evidence-based dental materials information that exist at this time.
      Anecdotal estimates of evidence for dental practice are in the range of 8 percent
      to 10 percent. While the process of evaluating the literature base for dental
      evidence began 20 years ago, it was not practical to implement it until high
      speed wireless connections, open access to journals, and omnipresent connections
      via smart phones became a reality. EBD includes five stages of information
      collection and analysis, starting with a careful definition of a clinical
      question using the PICO(T) approach. Clinical evidence in randomized control
      trials is considered the best. Clinical trial perspectives (prospective, cross
      sectional, retrospective) and outcome designs (RCTs, SCTs, CCTs, cohort studies,
      case-control studies) are quite varied. Aggregation techniques (including meta
      analyses) allow meaningful combinations of clinical data from trials with similar
      designs but with fewer rigors. Appraisals attempt to assess the entire evidence
      base without bias and answer clinical questions. Varying intensities to these
      approaches, Cochrane Collaboration, ADA-EBD Library, UTHSCSA CATs Library, are
      used to answer questions. Dental materials evidence from clinical trials is
      infrequent, short-term, and often not compliant with current guidelines
      (registration, CONSORT, PRISMA). Reports in current evidence libraries indicate
      less than 5 percent of evidence is related to restorative dental materials. 

PMID- 24571524
TI  - Reconsidering glass-ionomer cements for direct restorations.
AB  - Glass-ionomer cements (GICs) have been used in dentistry for a number of
      applications, primarily as a base or liner under other direct filling materials
      or indirect restorative materials, for crown buildup/foundation restorations, or
      as luting cements for indirect restorations. However, GICs have many unique
      attributes that make them useful for either a full-contour restoration or
      sandwich/hybrid restorations where they are synergistic with composite resins.
      This article, which includes two brief case reports, discusses the potential
      advantages of GIC for some direct applications where composite resin or other
      materials may not be the most ideal choice. 

PMID- 24571525
TI  - Classifying dental ceramics: numerous materials and formulations available for
      indirect restorations.
AB  - Because there are numerous ceramic systems available to clinicians for all types
      of indirect restorations, deciding which system works best for a given clinical
      situation can be a challenge. Understanding the different classifications of
      ceramic restoratives can be helpful not only to the clinician but also the dental
      technician. Manufacturers are constantly introducing newer ceramic materials and
      improving their existing systems, which has resulted in an increase in all
      ceramic restorations and fewer porcelain-to-metal restorations. The
      classification of ceramic materials remains mostly constant; however, it is
      subject to change based on newer materials and formulations. The classifications
      of ceramics are described using several different methods. 

PMID- 24571526
TI  - Influence of ceramic shades on surface hardness of different resin cements.
AB  - OBJETIVES: The aim of this study was to evaluate the effect of different ceramic
      spacer shades on the Knoop hardness (KH) of dual-cure resin cements (RelyX ARC
      RLX, 3M ESPE; Variolink II VLK, Ivoclar Vivadent) cured for 20 seconds with an
      LED light-curing unit. MATERIALS: Eight groups (n equals 15) were tested as
      follows: RelyX Control (light-cured without ceramic spacer); RelyX-2M2 ceramic
      spacer; RelyX-5M3 ceramic spacer; RelyX self-cured. Similar conditions were used
      with Variolink II cement. A microhardness tester was used to measure the KH
      values. Specimens were subjected to five 50 g/15 s indentations following curing
      at 0, 1, 2, 3, 4, 6, 24, 168, and 336 hours in order to determine the point at
      which the cements reach the maximum KH values. RESULTS: Control groups exhibited
      significantly higher KH values than the other groups (P less than 0.001) at 0 h
      following light curing. The KH values for RelyX-2M2 were not significantly
      different than the control group (P greater than 0.05) after 336 hours. All
      groups tested with 5M3 spacers had KH values that were not significantly
      different from the groups with self-cure mode, P greater than 0.05. The KH values
      for RelyX self-cure cement were significantly higher than Variolink II self-cure,
      P equals 0.003. RelyX-2M2 had KH values that were not significantly different
      from that of Variolink-2M2, P greater than 0.05. CONCLUSIONS: Ceramic spacer
      shades have tremendous effect on the KH values of RelyX and Variolink II. Darker
      ceramic shades (5M3 spacers) interfere with the absorption of light by the
      cements tested. In addition, the chemical portion in the self-cured mode is not
      sufficient to achieve optimum microhardness.

PMID- 24571528
TI  - Provisional material considerations: creating a blueprint of the final
      restorations.
AB  - Indirect restorative dentistry generally requires temporization of prepared teeth
      during the laboratory fabrication phase. Over the years, the physical properties
      of newer provisional materials have improved, which has enabled an expansion of
      the function of provisional restorations. Better strength, surface finish, and
      color match have increased their acceptability by patients and clinicians. In
      some clinical situations provisional restorations can provide information that is
      critical to the overall success of a case. Such information allows the clinician
      to verify and confirm with the patient the esthetics, phonetics, and function of
      the proposed anterior restorative treatment. The provisional restorations can
      also provide valuable information to the laboratory technician regarding design,
      contour, length, shade, and even correct articulation of the master model. The
      success of the definitive restoration is dependent on the accurate transfer of
      this information to the laboratory technician. 

PMID- 24571527
TI  - Versatile composite resins simplifying the practice of restorative dentistry.
AB  - After decades of technical development and refinement, composite resins continue
      to simplify the practice of restorative dentistry, offering clinicians
      versatility, predictability, and enhanced physical properties. With a wide range
      of products available today, composite resins are a reliable, conservative, multi
      functional restorative material option. As manufacturers strive to improve such
      properties as compression strength, flexural strength, elastic modulus,
      coefficient of thermal expansion, water sorption, and wear resistance, several
      classification systems of composite resins have been developed. 

PMID- 24571529
TI  - Equipping the operatory for maximum efficiency.

PMID- 24571530
TI  - A novel recessive mutation in the gene ELOVL4 causes a neuro-ichthyotic disorder
      with variable expressivity.
AB  - BACKGROUND: A rare neuro-ichthyotic disorder characterized by ichthyosis, spastic
      quadriplegia and intellectual disability and caused by recessive mutations in
      ELOVL4, encoding elongase-4 protein has recently been described. The objective of
      the study was to search for sequence variants in the gene ELOVL4 in three
      affected individuals of a consanguineous Pakistani family exhibiting features of
      neuro-ichthyotic disorder. METHODS: Linkage in the family was searched by
      genotyping microsatellite markers linked to the gene ELOVL4, mapped at chromosome
      6p14.1. Exons and splice junction sites of the gene ELOVL4 were polymerase chain
      reaction amplified and sequenced in an automated DNA sequencer. RESULTS: DNA
      sequence analysis revealed a novel homozygous nonsense mutation (c.78C > G;
      p.Tyr26*). CONCLUSIONS: Our report further confirms the recently described ELOVL4
      related neuro-ichthyosis and shows that the neurological phenotype can be absent
      in some individuals.

PMID- 24571532
TI  - Values beyond value? Is anything beyond the logic of capital?
AB  - We are living in a time when it is frequently assumed that the logic of capital
      has subsumed every single aspect of our lives, intervening in the organization of
      our intimate relations as well as the control of our time, including investments
      in the future (e.g. via debt). The theories that document the incursion of this
      logic (often through the terms of neoliberalism and/or governmentality) assume
      that this logic is internalized, works and organizes everything including our
      subjectivity. These theories performatively reproduce the very conditions they
      describe, shrinking the domain of values and making it subject to capital's
      logic. All values are reduced to value. Yet values and value are always dialogic,
      dependent and co-constituting. In this paper I chart the history by which value
      eclipses values and how this shrinks our sociological imagination. By outlining
      the historical processes that institutionalized different organizations of the
      population through political economy and the social contract, producing ideas of
      proper personhood premised on propriety, I detail how forms of raced, gendered
      and classed personhood was formed. The gaps between the proper and improper
      generate significant contradictions that offer both opportunities to and limits
      on capitals' lines of flight. It is the lacks, the residues, and the excess that
      cannot be captured by capital's mechanisms of valuation that will be explored in
      order to think beyond the logic of capital and show how values will always haunt
      value. 

PMID- 24571531
TI  - Primary tumor regression speed after radiotherapy and its prognostic significance
      in nasopharyngeal carcinoma: a retrospective study.
AB  - BACKGROUND: To observe the primary tumor (PT) regression speed after radiotherapy
      (RT) in nasopharyngeal carcinoma (NPC) and evaluate its prognostic significance.
      METHODS: One hundred and eighty-eight consecutive newly diagnosed NPC patients
      were reviewed retrospectively. All patients underwent magnetic resonance imaging
      and fiberscope examination of the nasopharynx before RT, during RT when the
      accumulated dose was 46-50 Gy, at the end of RT, and 3-4 months after RT.
      RESULTS: Of 188 patients, 40.4% had complete response of PT (CRPT), 44.7% had
      partial response of PT (PRPT), and 14.9% had stable disease of PT (SDPT) at the
      end of RT. The 5-year overall survival (OS) rates for patients with CRPT, PRPT,
      and SDPT at the end of RT were 84.0%, 70.7%, and 44.3%, respectively (P < 0.001,
      hazard ratio [HR] = 2.177, 95% confidence interval [CI] = 1.480-3.202). The 5
      year failure-free survival (FFS) and distant metastasis-free survival (DMFS)
      rates also differed significantly (87.8% vs. 74.3% vs. 52.7%, P = 0.001, HR =
      2.148, 95% CI, 1.384-3.333; 91.7% vs. 84.7% vs. 66.1%, P = 0.004, HR = 2.252, 95%
      CI = 1.296-3.912). The 5-year local relapse-free survival (LRFS) rates were not
      significantly different (95.8% vs. 86.0% vs. 81.8%, P = 0.137, HR = 1.975, 95%
      CI, 0.976-3.995). By multivariate analyses, the PT regression speed at the end of
      RT was the only independent prognostic factor of OS, FFS, and DMFS (P < 0.001, P
      = 0.001, and P = 0.004, respectively). The 5-year FFS rates for patients with
      CRPT during RT and CRPT only at the end of RT were 80.2% and 97.1%, respectively
      (P = 0.033). For patients with persistent PT at the end of RT, the 5-year LRFS
      rates of patients without and with boost irradiation were 87.1% and 84.6%,
      respectively (P = 0.812). CONCLUSIONS: PT regression speed at the end of RT was
      an independent prognostic factor of OS, FFS, and DMFS in NPC patients. Immediate
      strengthening treatment may be provided to patients with poor tumor regression at
      the end of RT.

PMID- 24571533
TI  - Promotion of full-thickness wound healing using epigallocatechin-3-O-gallate/poly
      (lactic-co-glycolic acid) membrane as temporary wound dressing.
AB  - Epigallocatechin-3-O-gallate (EGCG) is a major polyphenolic compound in green
      tea. It has been known that EGCG regulates the secretion of cytokines and the
      activation of skin cells during wound healing. In this study, various
      concentrations of EGCG were added to the electrospun membranes composed of poly
      (lactic-co-glycolic acid) (PLGA), and its healing effects on full-thickness
      wounds created in nude mice were investigated. The electrospun membranes
      containing 5 wt% EGCG (5EGCG/PLGA membrane) exhibited cytotoxicity in human
      dermal fibroblasts (HDFs) as HDF morphologies were transformed on them. In the
      animal study, cell infiltration of mice treated with electrospun membranes
      containing 1 wt% EGCG (1EGCG/PLGA membrane) significantly increased after 2
      weeks. The immunoreactivity of Ki-67 (re-epithelialization at the wound site) and
      CD 31 (formation of blood vessels) also increased in the mice treated with
      1EGCG/PLGA membranes in comparison with the mice treated with PLGA membranes.
      These results suggest that 1EGCG/PLGA can enhance wound healing in full thickness
      by accelerating cell infiltration, re-epithelialization, and angiogenesis. 

PMID- 24571534
TI  - The organization of spatial reference frames involved in the SNARC effect.
AB  - The SNARC effect refers to faster reaction times for larger numbers with right
      sided responses and for smaller numbers with left-sided responses, even when
      numerical magnitude is irrelevant. Although the SNARC is generally thought to
      reflect a mapping between numbers and space, the question of which spatial
      reference frame(s) are critical for the effect has not been systematically
      explored. We propose a dynamic hierarchical organization of the reference frames
      (from a global left-right frame to body- and object-related frames), where the
      influence of each frame can be modulated by experimental context. We conducted
      two experiments based on predictions derived from this organizational system.
      Experiment 1 compared instructions that differed only in focusing participants'
      attention on either the response buttons or the hands. Instructions focusing on a
      hand-based reference frame eliminated the SNARC. Experiment 2 provided the
      opportunity for an object-centred reference frame to manifest itself in the
      SNARC. Although we did not observe an effect of an object-centred reference
      frame, we observed the influence of other reference frames in a context where an
      object-centred reference frame was emphasized. Altogether, these results support
      the proposed organization of the reference frames. 

PMID- 24571535
TI  - 'They don't look at what affects us': the role of ecodevelopmental factors on
      alcohol and drug use among Latinos with physical disabilities.
AB  - Objectives. Latinos with disabilities disproportionately report substance use,
      including binge drinking and drug use. Ecodevelopmental factors, including
      socioeconomic patterning of poverty, social exclusion, and post-colonial racism,
      have been shown to impact alcohol and drug use. However, this line of research
      remains underdeveloped among Latinos with disabilities. The purpose of this study
      was to obtain rich descriptions of the role of ecodevelopmental factors,
      including family and community, on alcohol and drug use among Latinos with
      physical disabilities. Methods. We utilized a community-based participatory
      research design, in conjunction with an innovative methodology referred to as
      photovoice. Three rounds of photography and focus group interviews were conducted
      with a total of 17 focus groups. Reflections in each focus group interview were
      aloud and digitally audiotaped. A total of 28 participants 19-35 years of age
      (mean age = 27.65, SD = 5.48) participated in each round of photography and focus
      group interviews. Data analyses followed the tenets of descriptive phenomenology.
      Results. Findings highlight ecodevelopmental family and community risk and
      protective factors. At the family level, participants reflected on the ways in
      which family functioning, including family support, communication, and cohesion,
      can serve as risk and promotive factors for alcohol and drug use. Additionally,
      participants described in detail how experiences of poverty, stigma and
      discrimination, violence, accessibility to alcohol and drugs, accessibility for
      persons with disabilities, transportation, community support and cohesion, and
      access to health and mental health services constitute risk and promotive factors
      at the community level. Conclusion. Findings are suggestive of how
      ecodevelopmental family and community factors might increase the risk of alcohol
      and drug use among Latinos with physical disabilities. From this qualitative
      research, we derive a series of testable hypotheses. For example, future studies
      should examine the impact of family functioning on alcohol and drug use among
      Latinos with physical disabilities over time. Study findings may have great
      utility to inform the development of preventive interventions for this at-risk
      group. 

PMID- 24571536
TI  - SwissScoring--a nationwide survey of NEMS assessing practices and its accuracy.
AB  - BACKGROUND: The nine equivalents of nursing manpower use score (NEMS) is used to
      evaluate critical care nursing workload and occasionally to define hospital
      reimbursements. Little is known about the caregivers' accuracy in scoring, about
      factors affecting this accuracy and how validity of scoring is assured. METHODS:
      Accuracy in NEMS scoring of Swiss critical care nurses was assessed using case
      vignettes. An online survey was performed to assess training and quality control
      of NEMS scoring and to collect structural and organizational data of
      participating intensive care units (ICUs). Aggregated structural and procedural
      data of the Swiss ICU Minimal Data Set were used for matching. RESULTS: Nursing
      staff from 64 (82%) of the 78 certified adult ICUs participated in this survey.
      Training and quality control of scoring shows large variability between ICUs. A
      total of 1378 nurses scored one out of 20 case vignettes: accuracy ranged from
      63.7% (intravenous medications) to 99.1% (basic monitoring). Erroneous scoring
      (8.7% of all items) was more frequent than omitted scoring (3.2%). Mean NEMS per
      case was 28.0 +/- 11.8 points (reference score: 25.7 +/- 14.2 points). Mean bias
      was 2.8 points (95% confidence interval: 1.0-4.7); scores below 37.1 points were
      generally overestimated. Data from units with a greater nursing management staff
      showed a higher bias. CONCLUSION: Overall, nurses assess the NEMS score within a
      clinically acceptable range. Lower scores are generally overestimated. Inaccurate
      assessment was associated with a greater size of the nursing management staff.
      Swiss head nurses consider themselves motivated to assure appropriate scoring and
      its validation.

PMID- 24571537
TI  - Detection of a novel killer-cell immunoglobulin-like receptor allele -
      KIR3DL1*0150207 - in Asian individuals.
AB  - KIR3DL1*0150207 differs from KIR3DL1*0150201 at five nucleotide positions in
      introns 2, 3, 4 and 5, respectively. 

PMID- 24571538
TI  - An intervention to preschool children for reducing screen time: a randomized
      controlled trial.
AB  - BACKGROUND: Screen time, defined as time spent watching television, DVDs, or
      videos or playing computer or video games, has been related to serious health
      consequences in children, such as impaired language acquisition, violent
      behaviour, tobacco smoking and obesity. Our aim was to determine if a simple
      intervention aimed at preschool-aged children, applied at the health maintenance
      visits, in the primary care setting, would be effective in reducing screen time.
      METHODS: We used a two group randomized controlled trial design. Two- to 6-year
      old children and their parents were randomly assigned to receive an intervention
      to reduce their screen time, BMI and parental report of aggressive behaviour. At
      the end of the intervention we made home visits at 2, 6 and 9 months and the
      parents completed questionnaire. RESULTS: Parents in the intervention group
      reported less screen time and less aggressive behaviour than those in the control
      group but there were no differences in BMI z scores. CONCLUSIONS: This study
      shows that a preschool-based intervention can lead to reductions in young
      children's television/video viewing.

PMID- 24571539
TI  - Fully Bayesian inference under ignorable missingness in the presence of auxiliary
      covariates.
AB  - In order to make a missing at random (MAR) or ignorability assumption realistic,
      auxiliary covariates are often required. However, the auxiliary covariates are
      not desired in the model for inference. Typical multiple imputation approaches do
      not assume that the imputation model marginalizes to the inference model. This
      has been termed "uncongenial" [Meng (1994, Statistical Science 9, 538-558)]. In
      order to make the two models congenial (or compatible), we would rather not
      assume a parametric model for the marginal distribution of the auxiliary
      covariates, but we typically do not have enough data to estimate the joint
      distribution well non-parametrically. In addition, when the imputation model uses
      a non-linear link function (e.g., the logistic link for a binary response), the
      marginalization over the auxiliary covariates to derive the inference model
      typically results in a difficult to interpret form for the effect of covariates.
      In this article, we propose a fully Bayesian approach to ensure that the models
      are compatible for incomplete longitudinal data by embedding an interpretable
      inference model within an imputation model and that also addresses the two
      complications described above. We evaluate the approach via simulations and
      implement it on a recent clinical trial. 

PMID- 24571541
TI  - Chronic antibiotic-refractory diversion pouchitis successfully treated with
      leukocyteapheresis.

PMID- 24571540
TI  - Expression of HMGA2 in bladder cancer and its association with epithelial-to
      mesenchymal transition.
AB  - OBJECTIVES: High mobility group protein2 (HMGA2) and epithelial-to-mesenchymal
      transition are both related to progress of bladder cancer, however, the
      relationship between HMGA2, E-cadherin and vimentin in bladder cancer is not yet
      known. Thus, this study has examined expression of HMGA2, E-cadherin and vimentin
      in bladder cancer and investigated their relationship. MATERIALS AND METHODS: The
      5637 bladder cancer cell line and SV-HUC-1 normal uroepithelial cells were used
      to study expression of HMGA2, E-cadherin and vimentin using RT-PCR and western
      blotting. Paraffin wax-embedded bladder cancer tissues were used to study protein
      expression using immunohistochemistry and chi(2) analysis and Kendall's
      correlation were utilized statistical methods. RESULTS: Overexpression of HMGA2
      was associated with down-regulation of E-cadherin and up-regulation of vimentin
      in the 5637 bladder cancer line. A total of 49 paraffin wax-embedded tissues of
      transitional cell bladder cancer were used. Positive expression levels of HMGA2
      protein and vimentin were 41 and 43% in bladder tissues, respectively. No
      expression of E-cadherin was found in 43%. Expression of HMGA2, loss of E
      cadherin and expression of vimentin are all significantly correlated with bladder
      cancer grade and stage. Loss of E-cadherin and expression of vimentin both
      correlated with recurrence of the bladder cancer. CONCLUSIONS: Expression of
      HMGA2 was closely associated with occurrence of epithelial-to-mesenchymal
      transition. Expression of HMGA2, loss of E-cadherin and expression of vimentin
      may indicate high degree malignancy of bladder cancer. Loss of E-cadherin
      expression and positive expression of vimentin may predict recurrence of bladder
      cancer.

PMID- 24571542
TI  - An assessment of diabetes-related knowledge among registered nurses working in
      hospitals in Jordan.
AB  - BACKGROUND: Nurses play a vital role in caring for people with diabetes where
      knowledge constitutes the cornerstone of this care. AIM: This study assessed the
      level of Jordanian nurses' perceived and actual knowledge of diabetes and
      examined the relationship between nurses' actual knowledge of diabetes and their
      different characteristics. METHODS: A cross-sectional descriptive design was used
      to report knowledge regarding diabetes. Registered nurses were asked to complete
      self-administered questionnaires. The Diabetes Self-Report Tool and the Modified
      Diabetes Basic Knowledge Test were used to assess nurses' perceived and actual
      knowledge of diabetes. RESULTS: A total of 277 out of the 450 eligible registered
      nurses accepted to participate and returned questionnaires from seven hospitals
      in Jordan. Nurses in this study mostly demonstrated a knowledge deficit in
      clinical and theoretical-based topics, such as initial treatment of
      hypoglycaemia, insulin storage and preparation; meal planning and duration of
      action with hypoglycaemic agents. Nurses' actual knowledge of diabetes was
      positively correlated with their perceived knowledge, perceived competence and
      level of education. LIMITATIONS: Study participants were selected using
      convenience sampling. The length of time needed for nurses exceeded 50 min to
      complete study questionnaires. CONCLUSIONS: This study examined current knowledge
      among Jordanian registered nurses regarding diabetes. A knowledge deficit
      regarding diabetes was demonstrated by the nurses who participated in this study.
      The role of continuing education is essential to supporting nurses' knowledge of
      complex clinical conditions, such as diabetes. Adequate implementation and
      dissemination of evidence-based guidelines on caring for people with diabetes is
      a prerequisite to improve the nurses' knowledge. IMPLICATION FOR NURSING AND
      HEALTH POLICY: Promoting continuing education in diabetes for nurses requires
      continuous effort and creativity. Healthcare system administrators must
      acknowledge and prioritize the need for this education.

PMID- 24571543
TI  - Correction of esthetic and biomechanical outcomes after maxillary anterior single
      dental implant fracture: a case report.
AB  - Rehabilitation of the single anterior tooth in the esthetic region after a dental
      implant fracture requires management of contributing biomechanical and/or
      biological etiologic factors. The multidisciplinary treatment of a fractured
      maxillary anterior single dental implant with a staged, combined surgical and
      prosthetic approach is discussed. Alleviation of several, but not all, risk
      factors eliminated the need for replacement of gingiva with pink porcelain and
      maintained a stable post implant host complex. 

PMID- 24571544
TI  - Periodontal management and restoration of an amelogenesis imperfecta patient: a
      case report.
AB  - This report describes the treatment of a young male patient diagnosed with
      amelogenesis imperfecta (AI), a hereditary disorder that affects the enamel of
      both primary and permanent dentition. For management and rehabilitation, it is
      crucial to determine the type of AI-hypoplastic, hypomaturation, or
      hypocalcified. As with this patient, who presented with tricho-dento osseous
      syndrome, patients may present with associated expression of a syndrome (partial
      or full) and secondary changes in the periodontium. AI is a serious problem;
      therefore extensive treatment using a multidisciplinary approach must be
      instituted, especially if the patient is syndrome-associated. 

PMID- 24571545
TI  - Lowered parasympathetic activity in apparently healthy subjects with self
      reported symptoms of pain: preliminary results from a pilot study.
AB  - OBJECTIVES: The aim was to evaluate differences in the autonomic nervous system
      (ANS) activity, indexed by heart rate variability (HRV) in apparently healthy
      subjects with self-reported symptoms of pain (SRSP) within an exploratory
      analysis. METHODS: HRV data from 14 apparently healthy male individuals were
      analyzed to address potential differences in subjects with and without SRSP. SRSP
      was assessed using the four pain-related items from the symptom checklist (SCL
      90R). Subjects were stratified based on the presence of SRSP. RESULTS:
      Parasympathetic activity, indexed by pNN50, RMSSD, and high frequency (HF)
      spectrum of HRV, was lower in subjects with SRSP. Low frequency (LF) HRV and the
      LF/HF ratio were greater in subjects with SRSP. However, analysis of variance
      revealed no significant differences between the groups. Pearson correlations
      showed a correlation of pNN50, HF, LF, and LF/HF ratio and the presence and
      frequency of SRSP. Measures of parasympathetic activity (pNN50 and HF) were
      inversely associated with more SRSP, indicating that subjects with more frequent
      SRSP show decreased parasympathetic activity. CONCLUSIONS: Consistent with
      evidence on changes in HRV in patients with clinical conditions of chronic or
      recurrent pain, this is the first study to show that healthy individuals who
      report symptoms of pain may have lower parasympathetic activity revealed by
      measures of HRV.

PMID- 24571546
TI  - Risk of intracranial hemorrhage associated with autosomal dominant polycystic
      kidney disease in patients with end stage renal disease.
AB  - BACKGROUND: An analysis of intracranial hemorrhage (ICH) in a national sample of
      autosomal dominant polycystic kidney disease (ADPKD) patients receiving long-term
      dialysis has not been reported. It is often assumed that patients with ADPKD are
      not at increased risk of ICH after starting dialysis. We hypothesized that
      patients with ADPKD would have a higher subsequent risk of ICH even after the
      start of chronic dialysis. METHODS: Retrospective cohort study of Medicare
      primary patients with and without ADPKD in the United States Renal Data System
      (USRDS), initiated on chronic dialysis or transplanted between 1 January 1999 and
      3 July 2009, and followed until 31 December 2009. Covariates included age,
      gender, race, prior stroke, diabetes mellitus, dialysis modality, body mass
      index, serum albumin and other co-morbid conditions from the Medical Evidence
      Form. Primary outcome was ICH, based on inpatient and outpatient Medicare claims,
      and all-cause mortality. Kaplan-Meier analysis was used for unadjusted assessment
      of time to events. Cox regression was used for assessment of factors associated
      with ICH and mortality. We performed competing risk regression using kidney
      transplant and death as competing risks. Kidney transplant was also modeled as a
      time-dependent covariate in Cox regression. RESULTS: Competing risk regression
      demonstrated that ADPKD had a subhazard ratio 2.97 for ICH (95% CI 2.27-3.89).
      Adjusted Cox analysis showed that ADPKD patients had an AHR for death of 0.59 vs.
      non-ADPKD patients (95% CI 0.57-0.61). CONCLUSIONS: ADPKD is a significant risk
      factor for ICH among patients on maintenance dialysis. Our Medicare primary
      cohort was older than in previous studies of intracranial aneurysm rupture among
      ADPKD patients. There are also limitations inherent to using the USRDS database.

PMID- 24571547
TI  - Large-scale biomedical concept recognition: an evaluation of current automatic
      annotators and their parameters.
AB  - BACKGROUND: Ontological concepts are useful for many different biomedical tasks.
      Concepts are difficult to recognize in text due to a disconnect between what is
      captured in an ontology and how the concepts are expressed in text. There are
      many recognizers for specific ontologies, but a general approach for concept
      recognition is an open problem. RESULTS: Three dictionary-based systems (MetaMap,
      NCBO Annotator, and ConceptMapper) are evaluated on eight biomedical ontologies
      in the Colorado Richly Annotated Full-Text (CRAFT) Corpus. Over 1,000 parameter
      combinations are examined, and best-performing parameters for each system
      ontology pair are presented. CONCLUSIONS: Baselines for concept recognition by
      three systems on eight biomedical ontologies are established (F-measures range
      from 0.14-0.83). Out of the three systems we tested, ConceptMapper is generally
      the best-performing system; it produces the highest F-measure of seven out of
      eight ontologies. Default parameters are not ideal for most systems on most
      ontologies; by changing parameters F-measure can be increased by up to 0.4. Not
      only are best performing parameters presented, but suggestions for choosing the
      best parameters based on ontology characteristics are presented.

PMID- 24571548
TI  - An eEF1A1 truncation encoded by PTI-1 exerts its oncogenic effect inside the
      nucleus.
AB  - BACKGROUND: The oncogene PTI-1 was originally isolated from a prostate cancer
      cell line by its capability to transform rat fibroblasts. The PTI-1 mRNA has a
      very eccentric structure as the 5'UTR is similar to prokaryotic 23S rRNA, while
      the major open reading frame and the 3'UTR corresponds to a part of the mRNA
      encoding human translation elongation factor eEF1A1. Thus, the largest open
      reading frame encodes a truncated version of eEF1A1 lacking the first 67 amino
      acids, while having three unique N-terminal amino acids. Previously, the UTRs
      were shown to be a prerequisite for the transforming capacity of the PTI-1
      transcript. In this study, we have investigated the possible role of the UTRs in
      regulating protein expression and localization. METHODS: The protein expression
      profiles of a number of PTI-1 mRNA variants were studied in vitro and in vivo.
      Furthermore, the oncogenic potentials of the same PTI-1 mRNAs were determined by
      monitoring the capacities of stably transfected cells expressing these mRNAs to
      induce tumors in nude mice and form foci in cell culture. Finally, the cellular
      localizations of PTI-1 proteins expressed from these mRNAs were determined by
      fluorescence microscopy. RESULTS: The PTI-1 mRNA was found to give rise to
      multiple protein products that potentially originate from translation initiation
      at downstream, inframe AUGs within the major open reading frame. At least one of
      the truncated protein variants was also found to be oncogenic. However, the UTRs
      did not appear to influence the amount and identities of these truncated protein
      products. In contrast, our localization studies showed that the UTRs of the
      transcript promote a nuclear localization of the encoded protein(s). CONCLUSIONS:
      Translation of the PTI-1 mRNA results in multiple protein products of which (a)
      truncated variant(s) may play a predominant role during cellular transformation.
      The PTI-1 UTRs did not seem to play a role in translation regulation, but
      appeared to contribute to a nuclear localization of the PTI-1 protein(s). This
      indicates that the PTI-1 protein(s) exert(s) its/their oncogenic function inside
      the nucleus.

PMID- 24571549
TI  - Conserved charged residues at the surface and interface of epithelial sodium
      channel subunits--roles in cell surface expression and the sodium self-inhibition
      response.
AB  - The epithelial sodium channel (ENaC) is composed of three homologous subunits
      that form a triangular pyramid-shaped funnel, anchored in the membrane with a
      stem of six transmembrane domains. We examined the structure-function
      relationships of 17 conserved charged residues on the surface of the ectodomain
      of human gamma-ENaC subunit by alanine mutagenesis and co-expression with alpha-
      and beta-ENaC subunits in Xenopus oocytes. The results showed that Na(+)
      conductance of cells expressing these mutants can be accounted for by two
      parameters: (a) the ENaC density on the cell surface as measured by the
      fluorescence of an alpha-EnaC-yellow fluorescent protein hybrid and (b) the
      sodium self-inhibition (SSI) response that reflects the open probability of the
      channel (Po). Overall, the activity of all 17 mutants was correlated with surface
      levels of ENaC. There was no significant correlation between these parameters
      measured for alpha- and gamma-ENaC subunit mutants at nine homologous positions.
      Thus, the functions of most of the homologous surface residues examined differ
      between the two subunits. Only four mutants (K328, D510, R514 and E518)
      significantly reduced the SSI response. The alpha-ENaC homologs of three of these
      (R350, E530 and E538) also severely affected the SSI response. The cASIC1
      homologs of these (K247, E417, Q421) are located at the interface between
      subunits, on or about the ion pathway at the rotational symmetry axis in the
      center of the trimer. Thus, it is likely that these residues are involved in
      conformational changes that lead to channel constriction and the SSI response
      upon Na(+) ion flooding.

PMID- 24571550
TI  - Strategies and opportunities to STOP colon cancer in priority populations:
      pragmatic pilot study design and outcomes.
AB  - BACKGROUND: Colorectal-cancer is a leading cause of cancer death in the United
      States, and Latinos have particularly low rates of screening. Strategies and
      Opportunities to STOP Colon Cancer in Priority Populations (STOP CRC) is a
      partnership among two research institutions and a network of safety net clinics
      to promote colorectal cancer screening among populations served by these clinics.
      This paper reports on results of a pilot study conducted in a safety net
      organization that serves primarily Latinos. METHODS: The study assessed two
      clinic-based approaches to raise rates of colorectal-cancer screening among
      selected age-eligible patients not up-to-date with colorectal-cancer screening
      guidelines. One clinic each was assigned to: (1) an automated data-driven
      Electronic Health Record (EHR)-embedded program for mailing Fecal Immunochemical
      Test (FIT) kits (Auto Intervention); or (2) a higher-intensity program consisting
      of a mailed FIT kit plus linguistically and culturally tailored interventions
      delivered at the clinic level (Auto Plus Intervention). A third clinic within the
      safety-net organization was selected to serve as a passive control (Usual Care).
      Two simple measurements of feasibility were: 1) ability to use real-time EHR data
      to identify patients eligible for each intervention step, and 2) ability to offer
      affordable testing and follow-up care for uninsured patients. RESULTS: The study
      was successful at both measurements of feasibility. A total of 112 patients in
      the Auto clinic and 101 in the Auto Plus clinic met study inclusion criteria and
      were mailed an introductory letter. Reach was high for the mailed component
      (92.5% of kits were successfully mailed), and moderate for the telephone
      component (53% of calls were successful completed). After exclusions for invalid
      address and other factors, 206 (109 in the Auto clinic and 97 in the Auto Plus
      clinic) were mailed a FIT kit. At 6 months, fecal test completion rates were
      higher in the Auto (39.3%) and Auto Plus (36.6%) clinics compared to the usual
      care clinic (1.1%). CONCLUSIONS: Findings showed that the trial interventions
      delivered in a safety-net setting were both feasible and raised rates of
      colorectal-cancer screening, compared to usual care. Findings from this pilot
      will inform a larger pragmatic study involving multiple clinics. TRIAL
      REGISTRATION: ClinicalTrial.gov: NCT01742065.

PMID- 24571552
TI  - Identification of a novel HLA-DPB1 allele, HLA-DPB1*167:01, in a Chinese
      individual.
AB  - HLA-DPB1*167:01 allele differs from HLA-DPB1*10:01 by a single nucleotide
      substitution at codon 65 (ATC>CTC. 

PMID- 24571553
TI  - Disgust and biological descriptions bias logical reasoning during legal decision
      making.
AB  - Legal decisions often require logical reasoning about the mental states of people
      who perform gruesome behaviors. We use functional magnetic resonance imaging
      (fMRI) to examine how brain regions implicated in logical reasoning are modulated
      by emotion and social cognition during legal decision-making. Participants read
      vignettes describing crimes that elicit strong or weak disgust matched on
      punishment severity using the US Federal Sentencing Guidelines. An extraneous
      sentence at the end of each vignette described the perpetrator's personality
      using traits or biological language, mimicking the increased use of scientific
      evidence presented in courts. Behavioral results indicate that crimes weak in
      disgust receive significantly less punishment than the guidelines recommend.
      Neuroimaging results indicate that brain regions active during logical reasoning
      respond less to crimes weak in disgust and biological descriptions of
      personality, demonstrating the impact of emotion and social cognition on logical
      reasoning mechanisms necessary for legal decision-making. 

PMID- 24571554
TI  - Effect of oral contraceptives on lamotrigine levels depends on comedication.
AB  - OBJECTIVES: To evaluate prospectively the influence of cyclic oral contraceptive
      (OC) use on lamotrigine (LTG) serum levels when used in combination therapy.
      METHODS: Women with epilepsy using LTG in combination with valproate (VPA; n=7),
      carbamazepine (CBZ; n=3) or oxcarbazepine (OXC; n=1) were evaluated during two
      periods of 28 days cyclic OC use, monitoring antiepileptic drug (AED) levels
      every other day with the dried blood spot sampling method. Results were compared
      with women on LTG monotherapy and OCs (n=12). Pharmacokinetic analysis was
      performed using NONMEM software. RESULTS: Mean study population value of LTG
      clearance estimated by the final model was 3.17 l/h. Introduction of covariates
      for comedication (VPA, CBZ, OXC and OC) significantly reduced the between-subject
      variability. A significant influence of OC comedication on LTG clearance was seen
      in both LTG monotherapy (clearance with OC 4.02+/-0.38 l/h, OC-free week 3.03+/
      0.39 l/h) and in LTG-CBZ combination (clearance with OC 4.95+/-0.15 l/h, OC-free
      week 4.15+/-0.26 l/h). No influence of OC was found in LTG-VPA combination
      (clearance with OC 0.99+/-0.16 l/h, OC-free week 0.90+/-0.15 l/h). CONCLUSIONS:
      Adding OCs to LTG monotherapy or the combination LTG-CBZ significantly increased
      the LTG clearance and thus reduced LTG serum levels. In the combination LTG-CBZ,
      OCs had a non-significant effect on CBZ clearance. No significant influence of
      cyclic OC use on LTG or VPA clearance was found when these AEDs were used in
      combination.

PMID- 24571556
TI  - Estimating marginal properties of quantitative real-time PCR data using nonlinear
      mixed models.
AB  - A unified modeling framework based on a set of nonlinear mixed models is proposed
      for flexible modeling of gene expression in real-time PCR experiments. Focus is
      on estimating the marginal or population-based derived parameters: cycle
      thresholds and DeltaDeltac(t), but retaining the conditional mixed model
      structure to adequately reflect the experimental design. Additionally, the
      calculation of model-average estimates allows incorporation of the model
      selection uncertainty. The methodology is applied for estimating the differential
      expression of a phosphate transporter gene OsPT6 in rice in comparison to a
      reference gene at several states after phosphate resupply. In a small simulation
      study the performance of the proposed method is evaluated and compared to a
      standard method. 

PMID- 24571555
TI  - Daptomycin-loaded polymethylmethacrylate bone cement for joint arthroplasty
      surgery.
AB  - Antibiotic-loaded acrylic bone cement has been frequently used as an infection
      prophylaxis or antibiotic-loaded spacer in infected arthroplasty. In addition,
      daptomycin has been used recently against broad spectrum Gram-positive organisms.
      The goal of this in vitro study is to investigate the bacteriacidal and
      mechanical properties of daptomycin-incorporated polymethylmethacrylate (PMMA)
      bone cement and evaluate its feasibility for clinical use. Daptomycin (0.5, 1, or
      2 g) was premixed with 40 g of PMMA bone cement powder before curing. The
      mechanical properties of the daptomycin-loaded acrylic bone cement (DLABC) were
      estimated following standard guidance, and the release profile and kinetics of
      daptomycin from PMMA were analyzed. The antimicrobial efficacy of DLABC was
      determined with a zone of inhibition (ZOI) assay against Staphylococcus aureus,
      Staphylococcus epidermis, Enterococcus faecalis, and Enterococcus faecium,
      respectively. The results showed that the compressive strength, of PMMA bone
      cement, which was higher than 100 MPa in all groups, was sufficient according to
      ISO 5833 after incorporation of daptomycin. The encapsulated daptomycin was
      released for 2 weeks with a 9.59 +/- 0.85%, 15.25 +/- 0.69%, and 20.64 +/- 20.33%
      released percentage on the first day in the low, mid, and high groups,
      respectively. According to the calculated release kinetics, incorporated
      daptomycin should be 3.3 times the original dose to double its release. Although
      all recipes of DLABC had a microbial inhibitory effect, the effect with a higher
      encapsulated amount of daptomycin was more significant. Therefore, we believe
      that daptomycin can be locally delivered from PMMA bone cement at the surgical
      site as a prophylactic or treatment for osteomyelitis against Gram-positive
      organisms with intact cement function. 

PMID- 24571557
TI  - Using fiber-optic transillumination as a diagnostic aid in dental practice.
AB  - Fiber-optic transillumination (FOTI) is a well-accepted and valuable adjunctive
      diagnostic tool with a wide range of clinical applications. In dentistry, FOTI
      has been primarily associated with caries diagnosis and has been corroborated
      through research studies to be a valid indicator of the histological presence or
      absence of bacterially infected tooth structure. In this review, techniques for
      using FOTI for tooth evaluation are presented along with examples of how FOTI can
      be effectively used as a supplemental diagnostic aid. 

PMID- 24571558
TI  - Dental headache care and assessing and treating dental force-related problems.
AB  - An innovative assessment and treatment protocol system now enables dentists to
      more effectively and comprehensively assess and treat patients with chronic
      headache and migraine pain, as well as other dental force-related conditions. The
      system combines objective assessment with scientifically based, systematic, and
      predictable treatment methods and technologies to offer successful outcomes and
      maintenance. 

PMID- 24571559
TI  - Dentin hypersensitivity: differential diagnosis, tests, and etiology.
AB  - Dentin hypersensitivity (DHS) is a painful condition that affects up to 57
      percent of the adult population. It occurs as a result of exposure of dentin to
      the oral environment. Ensuring the correct diagnosis of this condition is based
      on history and examination. An oral screening for DHS should encompass such
      elements as patient history, clinical examination that includes radiographs, a
      variety of tests, identification of risk factors, and a differential diagnosis.
      An understanding of dentinal fluid and odontoblasts is also beneficial for
      diagnosis. 

PMID- 24571560
TI  - Extraction site preservation using new graft material that combines mineralized
      and demineralized allograft bone: a case series report with histology.
AB  - This retrospective case series reports on the use of a new allograft bone product
      composed of a 70 to 30 ratio of mineralized to demineralized cortical bone
      particles to preserve the alveolar ridge dimensions of patients requiring tooth
      extraction with plans for future dental implant placement. Ten patients received
      atraumatic tooth extractions with subsequent placement of the blended bone
      allograft. All sites were covered with a single layer of amnion-chorion, which
      was intentionally left exposed. After an average healing time of 14 weeks, the
      surgical sites were accessed for placement of dental implants. Prior to implant
      placement, trephine core samples were taken for histologic analysis. Dental
      implants were successfully placed in all previously grafted surgical sites; no
      sites required any additional bone augmentation. Histologic analysis of trephined
      bone core samples revealed bone compositions similar to those described in
      previously published site preservation studies. The results of this case series
      suggest that blended bone allograft containing a 70 to 30 ratio of mineralized to
      demineralized cortical bone particles can be successfully used to facilitate
      future placement of dental implants with as little as 14 weeks of healing. 

PMID- 24571562
TI  - Chairside CAD/CAM technology: a positive "disruption" in dentistry.

PMID- 24571561
TI  - Esthetics built to last: treatment of functional anomalies may need to precede
      esthetic corrections.
AB  - In this case of a 33 year-old male patient seeking a more esthetically pleasing
      smile, comprehensive restorative treatment planning included recognition of the
      patient's incisor position and morphology, dentofacial requirements, and
      appropriate vertical dimension. The accepted treatment plan consisted of
      orthodontic correction of the patient's anterior constriction, followed by
      placement of eight maxillary veneers and composite augmentation on the mandibular
      incisors and canines. Keys to achieving a successful outcome included knowledge
      of smile design, material selection, and preparation techniques. The case
      demonstrates how functional problems oftentimes must be addressed before esthetic
      correction can be made. 

PMID- 24571563
TI  - Adiponectin levels in hemodialysis patients.

PMID- 24571564
TI  - An education booklet to aid cardiac patients' recovery at home.
AB  - BACKGROUND: Hospital and home-based cardiac rehabilitation programmes improve the
      health outcomes of cardiac patients. Both types of programmes include patient
      education as a core component. However, many patients do not attend cardiac
      rehabilitation programmes for a variety of reasons. In Singapore, where cardiac
      rehabilitation is comparatively uncommon, patient education is usually delivered
      face-to-face by healthcare professionals because educational materials designed
      specifically for cardiac patients recovering at home are not available. AIM: This
      paper describes the development of a patient education booklet designed to aid
      recovery at home after a myocardial infarction in Singapore. METHODS: The
      conception and development of this evidence-based Heart Recovery Education
      Booklet was based on patient need and current clinical guidelines pertaining to
      cardiac rehabilitation and planned in consultation with specialists such as
      cardiologists, psychiatrists and physiotherapists. RESULTS: The booklet is a
      patient resource to aid recovery at home after an myocardial infarction. It is
      interactive, based on identified need and aims to guide and assist the patient in
      performing their usual activities of daily living and adhering to treatment
      regimens, including exercise. CONCLUSION: This booklet is a resource for patients
      with myocardial infarction and healthcare professionals and its effectiveness in
      improving health-related quality of life, psychological status and coronary risk
      profile is to be tested in a randomized controlled trial. IMPLICATIONS FOR
      NURSING AND HEALTH POLICY: Policy makers in health and nursing must find ways of
      developing and implementing cardiac rehabilitation programmes that aid recovery
      from myocardial infarction. This education booklet offers one way to do this.

PMID- 24571565
TI  - Pain is not systematically registered in Dutch medical oncology outpatients.
AB  - BACKGROUND: Systematic pain registration and assessment with a visual analog
      scale (VAS) or numeric rating scale (NRS) at each visit are key recommendations
      in one of the most recent guidelines on cancer pain management. It is unclear
      whether this recommendation is applied. OBJECTIVES: The aim was to explore
      registration of pain in medical records of patients visiting the medical oncology
      outpatient clinic. METHODS: In a multicenter study in six Dutch hospitals, data
      were extracted from medical records of 380 outpatients with cancer. Data of the
      first three visits at the outpatient clinic were studied. Descriptive statistics
      were conducted. RESULTS: In 23% of all 987 visits at the outpatient clinic, pain
      or absence of pain was registered, and in an additional 15%, a nonspecific
      symptom description was given. Regarding all other visits, (62%) pain or absence
      of pain was not documented at all. Pain measurement using a VAS or NRS was
      documented in only one visit. Pain was more often registered in medical records
      of patients with metastasis, as well as in those of patients with urogenital
      tumors. CONCLUSION: Pain in medical oncology outpatients is not systematically
      registered in their medical records. With one exception, pain was not registered
      with a VAS or NRS. Yet, registration and assessment of pain to monitor pain are
      essential to evaluate and adapt pain treatment over time. Pain registration has
      not improved since 2001 and therefore implementing the recommendations regarding
      systematic monitoring of pain is needed.

PMID- 24571566
TI  - The role of support and other factors in early breastfeeding cessation: an
      analysis of data from a maternity survey in England.
AB  - BACKGROUND: Although the majority of women in England initiate breastfeeding,
      approximately one third cease breastfeeding by six weeks and many of these women
      report they would like to have breastfed for longer. METHODS: Data from a survey
      of women >=16 years who gave birth to singleton term infants in 2009 in England;
      questionnaires were completed approximately three months postnatally. Logistic
      regression was used to investigate the association between postnatal support and
      other factors, and breastfeeding cessation at 10 days and six weeks. Population
      attributable fractions (PAFs) were calculated to estimate the relative
      contribution of breastfeeding support factors to overall breastfeeding cessation
      at these two time points. RESULTS: Of the 3840 women who initiated breastfeeding
      and reported timing of breastfeeding cessation, 13% had stopped by 10 days; and
      of the 3354 women who were breastfeeding at 10 days, 17% had stopped by six
      weeks. Socio-demographic factors (maternal age, ethnicity, country of birth,
      deprivation, education) and antenatal feeding intention were all independently
      associated with breastfeeding cessation at 10 days and six weeks. Women who did
      not receive feeding advice or support from a parent or peer support group,
      voluntary organisation, or breastfeeding clinic were more likely to stop
      breastfeeding by 10 days. Perceived active support and encouragement from
      midwives was associated with a lower odds of breastfeeding cessation at both 10
      days and six weeks. Estimated PAFs suggest that 34-59% of breastfeeding
      cessations by 10 days could be avoided if more women in the study population
      received breastfeeding support. CONCLUSION: Although multiple factors influence a
      mother's likelihood of continuing breastfeeding, it is clear that socio
      demographic factors are strongly associated with breastfeeding continuation.
      However, there is evidence that breastfeeding support, including that delivered
      by peer or lay support workers, may have an important role in preventing
      cessations in the first few weeks.

PMID- 24571568
TI  - Clinical and electroencephalographic findings in acutely ill adults with non
      convulsive vs convulsive status epilepticus.
AB  - BACKGROUND: Non-convulsive status epilepticus (NCSE) indicates a change in the
      mental state with no motor manifestations, being a clinical expression of
      prolonged epileptiform activity. In contrast to convulsive status epilepticus
      (CSE), no unified treatment recommendations have been proposed so far. We were
      interested to review the clinical and encephalographic characteristics in
      hospitalized patients with NCSE and CSE and compare their treatment and outcome.
      PATIENTS AND METHODS: The electroencephalographic recording records of adult
      patients with electrographic status epilepticus were retrieved. Patients'
      clinical records were then analyzed. RESULTS: Fifty-three patients with CSE and
      25 patients with NCSE were identified. Background diseases, neuroimaging findings
      and complications were similar in CSE and NCSE. Anoxia was a more frequent
      etiological factor only for myoclonic SE. Patients with CSE presented more often
      with coma. The number of drugs used for treatment was similar, but anesthetics
      drugs were administered more frequently in patients with CSE. The 30-day
      mortality rate was higher in myoclonic SE and generalized tonic-clonic SE, but
      the outcome on discharge in terms of survival and recovery was comparable between
      CSE and NCSE. CONCLUSIONS: The results of the present study show that the
      clinical parameters of NCSE in acutely ill patients do not substantially differ
      from those of patients with CSE. Moreover, despite more severe mental changes and
      the need for more anesthetic drugs for treatment of CSE, the final outcome did
      not differ between both groups. This might indicate that NCSE in acutely ill
      patients should be regarded as seriously as CSE.

PMID- 24571567
TI  - Gene duplication in an African cichlid adaptive radiation.
AB  - BACKGROUND: Gene duplication is a source of evolutionary innovation and can
      contribute to the divergence of lineages; however, the relative importance of
      this process remains to be determined. The explosive divergence of the African
      cichlid adaptive radiations provides both a model for studying the general role
      of gene duplication in the divergence of lineages and also an exciting foray into
      the identification of genomic features that underlie the dramatic phenotypic and
      ecological diversification in this particular lineage. We present the first
      genome-wide study of gene duplication in African cichlid fishes, identifying gene
      duplicates in three species belonging to the Lake Malawi adaptive radiation
      (Metriaclima estherae, Protomelas similis, Rhamphochromis "chilingali") and one
      closely related species from a non-radiated riverine lineage (Astatotilapia
      tweddlei). RESULTS: Using Astatotilapia burtoni as reference, microarray
      comparative genomic hybridization analysis of 5689 genes reveals 134 duplicated
      genes among the four cichlid species tested. Between 51 and 55 genes were
      identified as duplicated in each of the three species from the Lake Malawi
      radiation, representing a 38%-49% increase in number of duplicated genes relative
      to the non-radiated lineage (37 genes). Duplicated genes include several that are
      involved in immune response, ATP metabolism and detoxification. CONCLUSIONS:
      These results contribute to our understanding of the abundance and type of gene
      duplicates present in cichlid fish lineages. The duplicated genes identified in
      this study provide candidates for the analysis of functional relevance with
      regard to phenotype and divergence. Comparative sequence analysis of gene
      duplicates can address the role of positive selection and adaptive evolution by
      gene duplication, while further study across the phylogenetic range of cichlid
      radiations (and more generally in other adaptive radiations) will determine
      whether the patterns of gene duplication seen in this study consistently
      accompany rapid radiation.

PMID- 24571569
TI  - Kinematic evaluation of movement smoothness in golf: relationship between the
      normalized jerk cost of body joints and the clubhead.
AB  - BACKGROUND: When the human body is introduced to a new motion or movement, it
      learns the placement of different body parts, sequential muscle control, and
      coordination between muscles to achieve necessary positions, and it hones this
      new skill over time and repetition. Previous studies have demonstrated definite
      differences in the smoothness of body movements with different levels of
      training, i.e., amateurs compared with professionals. Therefore, we tested the
      hypothesis that skilled golfers swing a driver with a smoother motion than do
      unskilled golfers. In addition, the relationship between the smoothness of body
      joints and that of the clubhead was evaluated to provide further insight into the
      mechanism of smooth golf swing. METHODS: Two subject groups (skilled and
      unskilled) participated in the experiment. The skilled group comprised 20 male
      professional golfers registered with the Korea Professional Golf Association, and
      the unskilled group comprised 19 amateur golfers who enjoy golf as a hobby. Six
      infrared cameras (VICON460 system) were used to record the 3D trajectories of
      markers attached to the clubhead and body segments, and the resulting data was
      evaluated with kinematic analysis. A physical quantity called jerk was calculated
      to investigate differences in smoothness during downswing between the two study
      groups. RESULTS: The hypothesis that skilled golfers swing a driver with a
      smoother motion than do unskilled golfers was supported. The normalized jerk of
      the clubhead of skilled golfers was lower than that of unskilled golfers in the
      anterior/posterior, medial/lateral, and proximal/distal directions. Most human
      joints, especially in the lower body, had statistically significant lower
      normalized jerk values in the skilled group. In addition, the normalized jerk of
      the skilled group's lower body joints had a distinct positive correlation with
      the normalized jerk of the clubhead with r = 0.657 (p < 0.01). CONCLUSIONS: The
      result of this study showed that skilled golfers have smoother swings than
      unskilled golfers during the downswing and revealed that the smoothness of a
      clubhead trajectory is related more to the smoothness of the lower body joints
      than that of the upper body joints. These findings can be used to understand the
      mechanisms behind smooth golf swings and, eventually, to improve golf
      performance.

PMID- 24571570
TI  - Estimating acute air pollution health effects from cohort study data.
AB  - Traditional studies of short-term air pollution health effects use time series
      data, while cohort studies generally focus on long-term effects. There is
      increasing interest in exploiting individual level cohort data to assess short
      term health effects in order to understand the mechanisms and time scales of
      action. We extend semiparametric regression methods used to adjust for unmeasured
      confounding in time series studies to the cohort setting. Time series methods are
      not directly applicable since cohort data are typically collected over a
      prespecified time period and include exposure measurements on days without health
      observations. Therefore, long-time asymptotics are not appropriate, and it is
      possible to improve efficiency by exploiting the additional exposure data. We
      show that flexibility of the semiparametric adjustment model should match the
      complexity of the trend in the health outcome, in contrast to the time series
      setting where it suffices to match temporal structure in the exposure. We also
      demonstrate that pre-adjusting exposures concurrent with the health endpoints
      using trends in the complete exposure time series results in unbiased health
      effect estimation and can improve efficiency without additional confounding
      adjustment. A recently published article found evidence of an association between
      short-term exposure to ambient fine particulate matter (PM2.5 ) and retinal
      arteriolar diameter as measured by retinal photography in the Multi-Ethnic Study
      of Atherosclerosis (MESA). We reanalyze the data from this article in order to
      compare the methods described here, and we evaluate our methods in a simulation
      study based on the MESA data. 

PMID- 24571571
TI  - Practice patterns when treating patients with low back pain: a survey of physical
      therapists.
AB  - Low back pain (LBP), is a common musculoskeletal problem, affecting 75-85% of
      adults in their lifetime. Direct costs of LBP in the USA were estimated over 85
      billion dollars in 2005 resulting in a significant economic burden for the
      healthcare system. LBP classification systems and outcome measures are available
      to guide physical therapy assessments and intervention. However, little is known
      about which, if any, physical therapists use in clinical practice. The purpose of
      this study was to identify the use of and barriers to LBP classification systems
      and outcome measures among physical therapists in one state. A mixed methods
      study using a cross-sectional cohort design with descriptive qualitative methods
      was performed. A survey collected both quantitative and qualitative data relevant
      to classification systems and outcome measures used by physical therapists
      working with patients with LBP. Physical therapists responded using
      classification systems designed to direct treatment predominantly. The McKenzie
      method was the most frequent approach to classify LBP. Barriers to use of
      classification systems and outcome measures were lack of knowledge, too limiting
      and time. Classification systems are being used for decision-making in physical
      therapy practice for patients with LBP. Lack of knowledge and training seems to
      be the main barrier to the use of classification systems in practice. The
      Oswestry Disability Index and Numerical Pain Scale were the most commonly used
      outcome measures. The main barrier to their use was lack of time. Continuing
      education and reading the literature were identified as important tools to teach
      evidence-based practice to physical therapists in practice.

PMID- 24571572
TI  - Separate assessment of gluteus medius and minimus: B-mode or M-mode ultrasound?
AB  - The hip abductors gluteus medius (Gmed) and minimus (Gmin) differ slightly in
      function and how they are affected by hip joint pathology. A separate assessment
      of Gmed and Gmin is feasible by ultrasound (US) imaging. B-mode and M-mode US can
      be used to measure muscle thickness. Two B- and two M-mode scans of Gmed and Gmin
      thickness were taken in relaxation on 16 asymptomatic volunteers, repeated within
      4 days on 11 subjects. Three types of intra-rater reliability of muscle thickness
      measurements were examined: (1) within-session reliability comparing two scans
      from the same session, (2) between-days reliability comparing thickness from two
      scanning occasion within 4 days and (3) reliability of taking thickness
      measurements by re-measuring the same US scans after 1 week. Thickness
      measurements on B- and M-mode images provided ICC3,1 >0.96 for within-session
      reliability. ICC3,k >0.89 for between-days reliability and ICC3,1 >0.85 for re
      reading the same scans were estimated. Minimal detectable changes >1.0 mm within
      session, >2.4 mm between-days and >1.7 mm for re-reading scans indicated that
      small thickness changes are not detectable. The investigation suggests a slight
      advantage for fascia recognition in B-mode and the advantage of visual control of
      muscle relaxation in M-mode.

PMID- 24571573
TI  - The GAR domain of GAS2L3 mediates binding to the chromosomal passenger complex
      and is required for localization of GAS2L3 to the constriction zone during
      abscission.
AB  - GAS2L3 is a recently identified tubulin- and actin-binding protein that regulates
      cytokinesis and abscission. In this study we show that GAS2L3 interacts with the
      chromosomal passenger complex (CPC), which plays key roles in mitosis and
      cytokinesis. Biochemical assays show that GAS2L3 directly interacts with the C
      terminus of borealin and the N-terminus of survivin. We find that the interaction
      between these two CPC subunits and GAS2L3 is mediated by the conserved GAR domain
      of GAS2L3. We further show that the GAR domain of GAS2L3 is required for
      localization of GAS2L3 to the constriction zone. Taken together these data
      suggest that GAS2L3 is a downstream effector of the CPC during cytokinetic
      abscission. 

PMID- 24571574
TI  - Synthesis and anticonvulsant activity of ethyl 2,2-dimethyl-1-(2
      substitutedhydrazinecarboxamido) cyclopropanecarboxylate derivatives.
AB  - In this study on the development of new anticonvulsants, fourteen ethyl 2,2
      dimethyl-1-(2-substitutedhydrazinecarboxamido) cyclopropanecarboxylate
      derivatives were synthesized and tested for anticonvulsant activity using the
      maximal electroshock, subcutaneous pentylenetetrazole screens, which are the most
      widely employed seizure models for early identification of candidate
      anticonvulsants. Their neurotoxicity was determined applying the rotorod test.
      Two compounds 6f and 6k showed promising anticonvulsant activities in both models
      employed for anticonvulsant evaluation. The most active compound 6k showed the
      maximal electroshock-induced seizures with ED50 value of 9.2 mg/kg and TD50 value
      of 387.5 mg/kg after intraperitoneally injection to mice, which provided compound
      6k with a protective index (TD50/ED50 ) of 42.1 in the maximal electroshock test.

PMID- 24571575
TI  - Characterization of subepithelial interstitial cells in normal and pathological
      human prostate.
AB  - AIMS: To characterize the subepithelial (SE) stromal cells in normal human
      prostate and to study phenotypical changes in these SE stromal cells in benign
      prostate hyperplasia (BPH) and prostate cancer (PCa). METHODS AND RESULTS: Tissue
      was obtained from normal, hyperplastic and tumoral areas in prostatectomy
      specimens. Tissue samples were processed for morphology, immunohistochemistry,
      immunofluorescence and electron microscopy. An ultrastructural and
      immunohistochemical phenotype for the SE stromal cells was assessed, and changes
      occurring in BPH and PCa were looked for. Based on the ultrastructural findings
      the dominant SE stromal cell types in normal prostate were interstitial Cajal
      like cells and spindle-shaped myoid cells with both myoid and fibroblastic
      features. An immunohistochemical correlate was found with selective expression of
      mesenchymal and myoid cell markers. In BPH and PCa, a changed stromal cell
      composition of the SE region was found. Furthermore, direct contacts between
      spindle-shaped myoid cells and tumour cells were observed in PCa. CONCLUSIONS:
      The present study shows for the first time that the SE area in the human prostate
      houses different stromal cell types with distinct phenotypes. In BPH and PCa
      specific disease-related changes were observed in the organization and phenotypes
      of SE interstitial cells.

PMID- 24571577
TI  - Large, segmental, circular vascular malformation of the small intestine (in a
      female toddler with hematochezia): unusual presentation in a child.
AB  - BACKGROUND: Failure to thrive and hematochezia in children may be alarm signs
      warranting endoscopy. In contrast, vascular malformations of the small intestine
      are uncommon in this age group. We report on a female toddler in whom various
      imaging techniques revealed an unusually large segmental vascular malformation of
      the ileum as the cause of the child's main clinical symptoms. CASE PRESENTATION:
      A 19 months old girl presented with severe anemia (Hb 3 mmol/l), failure to
      thrive and chronic diarrhea. Diagnostics for intestinal blood loss and pathogens
      were negative. The child had duodenoscopy, also for histological diagnosis of
      celiac disease, with negative results. A dietary protocol was suggestive for
      inadequate iron intake and she was supplemented. After symptomless four-months
      the child presented again, now with mild abdominal pain and, for the first time,
      hematochezia. An orienting abdominal ultrasound (US) study showed a suspicious
      tumorous bowel condition. A subsequent detailed abdominal US supplemented by a
      saline enema during investigation (i.e., "hydrocolon", to improve outlining of
      the formation's localization) revealed a large circumferential cystiform vascular
      mass of the ileum causing segmental ileal obstruction.Complementing preoperative
      abdominal hydro-MRI, planned based on the findings of the US study, confirmed the
      suspected vascular malformation of the ileum and exquisitely outlined the extent,
      location and anatomy.The patient was successfully operated laparoscopically, the
      affected ileum segment with the mass was completely removed as proven by
      histology, and the child recovered well. CONCLUSIONS: The huge segmental vascular
      malformation of the distal ileum described here is an extreme rarity in young
      children. Although the reported child's presenting symptoms malabsorption and
      malnutrition could have been responsible for its severe anemia, this was
      obviously caused by blood losses from the ileal vascular malformation. It was due
      to incipient abdominal pain rather than hematochezia that abdominal US was
      performed and proved crucial for correctly diagnosing this rare malformation.
      Even in this extensive case detailed imaging work-up including adapted MRI added
      all information necessary for minimal invasive laparoscopic en bloc resection.

PMID- 24571576
TI  - 3-D ultrastructure and collagen composition of healthy and overloaded human
      tendon: evidence of tenocyte and matrix buckling.
AB  - Achilles tendinopathies display focal tissue thickening with pain and
      ultrasonography changes. Whilst complete rupture might be expected to induce
      changes in tissue organization and protein composition, little is known about the
      consequences of non-rupture-associated tendinopathies, especially with regards to
      changes in the content of collagen type I and III (the major collagens in
      tendon), and changes in tendon fibroblast (tenocyte) shape and organization of
      the extracellular matrix (ECM). To gain new insights, we took biopsies from the
      tendinopathic region and flanking healthy region of Achilles tendons of six
      individuals with clinically diagnosed tendinopathy who had no evidence of
      cholesterol, uric acid and amyloid accumulation. Biochemical analyses of collagen
      III/I ratio were performed on all six individuals, and electron microscope
      analysis using transmission electron microscopy and serial block face-scanning
      electron microscopy were made on two individuals. In the tendinopathic regions,
      compared with the flanking healthy tissue, we observed: (i) an increase in the
      ratio of collagen III : I proteins; (ii) buckling of the collagen fascicles in
      the ECM; (iii) buckling of tenocytes and their nuclei; and (iv) an increase in
      the ratio of small-diameter : large-diameter collagen fibrils. In summary, load
      induced non-rupture tendinopathy in humans is associated with localized
      biochemical changes, a shift from large- to small-diameter fibrils, buckling of
      the tendon ECM, and buckling of the cells and their nuclei.

PMID- 24571578
TI  - Effects of cranial electrical stimulation on activity in regions of the basal
      ganglia in individuals with fibromyalgia.

PMID- 24571579
TI  - A new HLA-A*02 allele, A*02:465.
AB  - The new allele A*02:465 showed one nucleotide difference with A*02:06:01
      (172G>A). 

PMID- 24571580
TI  - Step counter use in type 2 diabetes: a meta-analysis of randomized controlled
      trials.
AB  - BACKGROUND: While step counter use has become popular among type 2 diabetes (T2D)
      patients, its effectiveness in increasing physical activity (PA) and improving
      glycemic control has been poorly defined. The aim of this meta-analysis of
      randomized controlled trials (RCTs) was to evaluate the association of step
      counter use with PA and glycemic control in T2D patients. METHODS: Articles were
      identified by searches of PubMed, Web of Science and Cochrane Library from
      January 1994 to June 2013. RCTs in the English language were included, if they
      had assessed the effectiveness of step counters as motivating and monitoring
      tools in T2D patients, with reported changes in steps per day (steps/d) or
      glycosylated hemoglobin A1c (HbA1c), or both. Data were independently collected
      by 2 authors and overall estimates were made by a random-effects model. RESULTS:
      Of the 551 articles retrieved, 11 RCTs were included. Step counter use
      significantly increased PA by 1,822 steps/d (7 studies, 861 participants; 95%
      confidence interval (CI): 751 to 2,894 steps/d) in patients with T2D. Step
      counter use with a PA goal showed a bigger increase in PA (weighted mean
      difference (WMD) 3,200 steps/d, 95% CI: 2,053 to 4,347 steps/d) than without (WMD
      598 steps/d, 95% CI: -65 to 1,260 steps/d). Further subgroup analysis suggested
      step counter use with a self-set PA goal (WMD 2,816 steps/d, 95% CI: 1,288 to
      4,344 steps/d) made no difference in increasing PA from a 10,000 steps/d goal
      (WMD 3,820 steps/d, 95% CI: 2,702 to 4,938 steps/d). However, no significant
      HbA1c change was observed by step counter use (10 studies, 1,423 participants;
      WMD 0.02%, 95% CI: -0.08% to 0.13%), either with (WMD 0.04%, 95% CI: -0.21% to
      0.30%) or without a PA goal (WMD 0.01%, 95% CI: -0.10% to 0.13%). CONCLUSIONS:
      Step counter use is associated with a significant increase in PA in patients with
      T2D. However, evidence regarding its effect in improving glycemic control remains
      insufficient. TRIAL REGISTRATION: PROSPERO CRD42013005236.

PMID- 24571581
TI  - SNPhylo: a pipeline to construct a phylogenetic tree from huge SNP data.
AB  - BACKGROUND: Phylogenetic trees are widely used for genetic and evolutionary
      studies in various organisms. Advanced sequencing technology has dramatically
      enriched data available for constructing phylogenetic trees based on single
      nucleotide polymorphisms (SNPs). However, massive SNP data makes it difficult to
      perform reliable analysis, and there has been no ready-to-use pipeline to
      generate phylogenetic trees from these data. RESULTS: We developed a new
      pipeline, SNPhylo, to construct phylogenetic trees based on large SNP datasets.
      The pipeline may enable users to construct a phylogenetic tree from three
      representative SNP data file formats. In addition, in order to increase
      reliability of a tree, the pipeline has steps such as removing low quality data
      and considering linkage disequilibrium. A maximum likelihood method for the
      inference of phylogeny is also adopted in generation of a tree in our pipeline.
      CONCLUSIONS: Using SNPhylo, users can easily produce a reliable phylogenetic tree
      from a large SNP data file. Thus, this pipeline can help a researcher focus more
      on interpretation of the results of analysis of voluminous data sets, rather than
      manipulations necessary to accomplish the analysis.

PMID- 24571582
TI  - Effects of chemical castration on sex offenders in relation to the kinetics of
      serum testosterone recovery: implications for dosing schedule.
AB  - INTRODUCTION: A growing number of countries are adopting chemical castration as
      treatment and penalty for sex offenders. AIM: The aim of this study is to
      evaluate the outcome of chemical castration of sexual offenders with a focus on
      the kinetics of serum testosterone (T) recovery. METHODS: This prospective
      analysis included 56 sex offenders imprisoned for sexual offenses at the National
      Forensic Hospital. Thirty-eight and 18 patients who received 3 and 6 months of
      leuprolide acetate injections were assigned to group A and group B, respectively.
      MAIN OUTCOME MEASURES: To evaluate treatment efficacy according treatment
      duration, psychobehavioral assessments and serum T levels were serially measured
      during the on-cycle and the following observational 12-month off-cycle. RESULTS:
      Chemical castration and the associated decrease in serum T levels reduced the
      frequency and intensity of sexual thoughts in 76% and 71% of group A patients and
      in 78% and 72% of group B patients, respectively. Reductions in masturbation
      frequency were observed in 74% of group A and 83% of group B patients. The median
      Wilson's Sex Fantasy Questionnaire (SFQ) scores were also significantly reduced
      in both groups. In group A, an upsurge of serum T to the flare level was observed
      during the first 2 months of the off-cycle, accompanied by an intense sexual
      drive and fantasy. In group B, serum T gradually recovered to the baseline level
      and continued to upsurge beyond baseline levels during the observational period.
      SFQ scores of group A returned to pretreatment levels following the observational
      period; however, SFQ scores of group B remained suppressed. Lack of objective
      assessments for psychobehavioral outcomes was a limitation. CONCLUSIONS: The
      efficacy of chemical castration varied according to the treatment duration.
      Regarding the kinetics of serum T recovery, maintaining at least 6 months of
      treatment warranted stable control of an excessive sexual drive following
      treatment cessation.

PMID- 24571583
TI  - Mapping potential groundwater-dependent ecosystems for sustainable management.
AB  - Ecosystems which rely on either the surface expression or subsurface presence of
      groundwater are known as groundwater-dependent ecosystems (GDEs). A comprehensive
      inventory of GDE locations at an appropriate management scale is a necessary
      first-step for sustainable management of supporting aquifers; however, this
      information is unavailable for most areas of concern. To address this gap, this
      study created a two-step algorithm which analyzed existing geospatial and remote
      sensing data to identify potential GDEs at both state/province and aquifer/basin
      scales. At the state/province scale, a geospatial information system (GIS)
      database was constructed for Texas, including climate, topography, hydrology, and
      ecology data. From these data, a GDE index was calculated, which combined
      vegetative and hydrological indicators. The results indicated that central Texas,
      particularly the Edwards Aquifer region, had highest potential to host GDEs.
      Next, an aquifer/basin scale remote sensing-based algorithm was created to
      provide more detailed maps of GDEs in the Edwards Aquifer region. This algorithm
      used Landsat ETM+ and MODIS images to track the changes of NDVI for each
      vegetation pixel. The NDVI dynamics were used to identify the vegetation with
      high potential to use groundwater--such plants remain high NDVI during extended
      dry periods and also exhibit low seasonal and inter-annual NDVI changes between
      dry and wet seasons/years. The results indicated that 8% of natural vegetation
      was very likely using groundwater. Of the potential GDEs identified, 75% were
      located on shallow soil averaging 45 cm in depth. The dominant GDE species were
      live oak, ashe juniper, and mesquite.

PMID- 24571584
TI  - The university of Virginia/Padova type 1 diabetes simulator matches the glucose
      traces of a clinical trial.
AB  - BACKGROUND: In 2008, the Food and Drug Administration (FDA) accepted our type 1
      diabetes mellitus (T1DM) simulator (S2008), equipped with 100 in silico adults,
      100 adolescents, and 100 children, as a substitute for preclinical trials for
      certain insulin treatments, including closed-loop algorithms. Hypoglycemia was
      well described in the simulator, but recent closed-loop trials showed a much
      larger frequency of hypoglycemia events in patients compared with the in silico
      ones. In order to better describe the distribution of glucose concentration
      observed in clinical trials, the simulator has recently been updated, and
      modifications have been accepted by the FDA (S2013). The aim of this study is to
      assess the validity of the S2013 simulator against clinical data and compare its
      performance with that of the S2008. SUBJECTS AND METHODS: The database consists
      of 24 T1DM subjects who received dinner (70.7+/-3.3 g of carbohydrate) and
      breakfast (52.9+/-0.1 g of carbohydrate) in two occasions (open- and closed
      loop), for a total of 96 postmeal glucose profiles. Measured plasma glucose
      profiles were compared with those simulated in 100 in silico adults, and the
      continuous glucose error grid analysis (CG-EGA) was used to assess the validity
      of the simulated traces. Moreover, the most common outcome metrics have been
      compared. RESULTS: The frequency of hypoglycemia episodes predicted by the S2013
      well reproduces that observed during clinical trials as proven by the CG-EGA. In
      addition, the outcome metrics provided by the S2013 are similar to those observed
      in clinical trials in a set of T1DM subjects. CONCLUSIONS: We demonstrated that
      the virtual subjects of the S2013 are representative of the T1DM population
      observed in a clinical trial. We conclude that the S2013 is a valid tool usable
      to test the robustness of closed-loop control algorithms for artificial pancreas.

PMID- 24571585
TI  - A unique bleeding-related complication of sorafenib, a tyrosine kinase inhibitor,
      in advanced hepatocellular carcinoma: a case report.
AB  - INTRODUCTION: Sorafenib, a multikinase inhibitor as a standard of care for
      advanced hepatocellular carcinoma, may lead endothelial cells to an unstable
      state by blocking the signaling pathway of vascular endothelial growth factor
      receptor, which may result in the disruption of the architecture and integrity of
      the microvasculature, and eventually increase the risk of hemorrhage. Hemobilia
      is a relatively uncommon condition as a consequence of hepatocellular carcinoma
      and its risk factors remain uncertain. CASE PRESENTATION: Here we report a unique
      case of hemobilia occurring in a 55-year-old Korean man with hepatitis B virus
      related hepatocellular carcinoma on Barcelona Clinic Liver Cancer advanced stage
      after seven days of treatment with sorafenib. He had received prior radiation
      therapy. Endoscopy revealed bleeding from the major duodenal papilla and
      endoscopic retrograde cholangiography revealed an amorphous filling defect
      throughout the common bile duct. Blood clots were removed by balloon sweeping and
      a nasobiliary drainage tube was placed. No further bleeding has been detected as
      of eight months after discontinuation of sorafenib. CONCLUSION: Sorafenib may
      increase the risk of biliary bleeding in hepatocellular carcinoma patients who
      were primed with irradiation, by blocking the signaling pathway of the vascular
      endothelial growth factor receptor. Therefore, sorafenib should be used with
      caution in patients with advanced hepatocellular carcinoma, especially when
      combined with radiation therapy.

PMID- 24571586
TI  - Ultrahigh dimensional time course feature selection.
AB  - Statistical challenges arise from modern biomedical studies that produce time
      course genomic data with ultrahigh dimensions. In a renal cancer study that
      motivated this paper, the pharmacokinetic measures of a tumor suppressor (CCI
      779) and expression levels of 12,625 genes were measured for each of 33 patients
      at 8 and 16 weeks after the start of treatments, with the goal of identifying
      predictive gene transcripts and the interactions with time in peripheral blood
      mononuclear cells for pharmacokinetics over the time course. The resulting data
      set defies analysis even with regularized regression. Although some remedies have
      been proposed for both linear and generalized linear models, there are virtually
      no solutions in the time course setting. As such, a novel GEE-based screening
      procedure is proposed, which only pertains to the specifications of the first two
      marginal moments and a working correlation structure. Different from existing
      methods that either fit separate marginal models or compute pairwise correlation
      measures, the new procedure merely involves making a single evaluation of
      estimating functions and thus is extremely computationally efficient. The new
      method is robust against the mis-specification of correlation structures and
      enjoys theoretical readiness, which is further verified via Monte Carlo
      simulations. The procedure is applied to analyze the aforementioned renal cancer
      study and identify gene transcripts and possible time-interactions that are
      relevant to CCI-779 metabolism in peripheral blood.

PMID- 24571587
TI  - Interferon beta-1a reduces increased interleukin-16 levels in multiple sclerosis
      patients.
AB  - OBJECTIVES: There is convergent evidence for an important role of interleukin-16
      (IL-16) in the pathogenesis of multiple sclerosis (MS). IL-16 serves as a
      chemoattractant for different immune cells that are involved in developing
      lesions. Here, we compared IL-16 levels of MS patients and controls and addressed
      the long-term effect of IFN-beta, the most common immunomodulatory MS therapy, on
      IL-16 serum levels in MS patients over 2 years. Beyond this, we analysed the
      expression of IL-16 in two CD4(+) T-cell subsets, Th1 and Th17 cells, which are
      important autoimmune mediators and affected by IFN-beta treatment, derived from
      myelin-specific T-cell transgenic mice. MATERIALS AND METHODS: IL-16 serum levels
      of 17 controls and of 16 MS patients before therapy and at months 1, 2, 3, 6, 9,
      12 and 24 during IFN-beta1a therapy were determined by ELISA. MRI was performed
      before therapy, at months 12 and 24. IL-16 expression of in vitro differentiated
      murine myelin oligodendrocyte glycoprotein (MOG)-specific Th1 and Th17 cells was
      quantified by real-time PCR. RESULTS: Before therapy, MS patients showed
      significantly elevated IL-16 levels compared with controls irrespective of
      disease activity determined by MRI. Therapy with IFN-beta1a led to a significant
      linear decrease in IL-16 serum levels beginning after 2 months. MOG-specific Th17
      cells expressed more IL-16 than Th1 cells. CONCLUSIONS: Reduction in increased IL
      16 levels may be of relevance for the therapeutic effect of IFN-beta1a in MS.
      Easily accessible IL-16 serum levels hold a potential as biomarker of treatment
      efficacy in MS.

PMID- 24571590
TI  - How we created a targeted teaching tool using blog architecture for anesthesia
      and critical care education--the A/e anesthesia exchange blog.
AB  - BACKGROUND: The time constraints on a clinical educator have increased immensely
      over the past decade. Technology has served to significantly bridge the challenge
      over the past decade. WHAT WE DID: We created a method of delivering targeted
      educational content for point of care learning in anesthesia and critical care.
      Our blog platform allows clinician-educators to deliver content as videopodcasts
      and presentations to learners in a straightforward and easily accessible manner
      both on the web and through mobile platforms. The A/e Anesthesia exchange
      "pushed" content at predetermined time intervals to learners and content was
      based on timely topics that were clinically relevant to their daily practice. The
      A/e Blog allowed multiple authors across disciplines to contribute content, thus
      providing learners potentially access to resources of knowledge from the entire
      team of clinician-educators at an institution. During the pilot phase of A/e blog
      implementation, the authors gained valuable insights into the use and limitations
      of web-based technology as a teaching tool. These included challenges with
      faculty and student participation, managing techno stress of faculty not fluent
      with the technology, tailoring content based on analytics data and web platform
      robustness and spam protection. CONCLUSION: With these insights in hand, we
      anticipate the launch of an even more robust A/e: Anesthesia Exchange (version
      2.0) by the end of 2013.

PMID- 24571591
TI  - Ormosil gels doped with engineered catechol 1,2 dioxygenases for chlorocatechol
      bioremediation.
AB  - Enzymes entrapped in wet, nanoporous silica gel have great potential as
      bioreactors for bioremediation because of their improved thermal, chemical, and
      mechanical stability with respect to enzymes in solution. The B isozyme of
      catechol 1,2 dioxygenase from Acinetobacter radioresistens and its mutants of
      Leu69 and Ala72, designed for an increased reactivity toward the environmental
      pollutant chlorocatechols, were encapsulated using alkoxysilanes and alkyl
      alkoxysilanes as precursors in varying proportions. Encapsulation of the mutants
      in a hydrophobic tetramethoxysilane/dimethoxydimethylsilane-based matrix yielded
      a remarkable 10- to 12-fold enhancement in reactivity toward chlorocatechols.
      These gels also showed a fivefold increase in relative reactivity toward
      chlorocatechols with respect to the natural substrate catechol, thus compensating
      for their relatively low activity for these substrates in solution. The
      encapsulated enzyme, unlike the enzyme in solution, proved resilient in assays
      carried out in urban wastewater and bacteria-contaminated solutions mimicking
      environmentally relevant conditions. Overall, the combination of a structure
      based rational design of enzyme mutants, and the selection of a suitable
      encapsulation material, proved to be a powerful approach for the production and
      optimization of a potential bioremediation device, with increased activity and
      resistance toward bacterial degradation. 

PMID- 24571592
TI  - Blue skin.

PMID- 24571588
TI  - Systematic analysis of 18F-FDG PET and metabolism, proliferation and hypoxia
      markers for classification of head and neck tumors.
AB  - BACKGROUND: Quantification of molecular cell processes is important for
      prognostication and treatment individualization of head and neck cancer (HNC).
      However, individual tumor comparison can show discord in upregulation
      similarities when analyzing multiple biological mechanisms. Elaborate tumor
      characterization, integrating multiple pathways reflecting intrinsic and
      microenvironmental properties, may be beneficial to group most uniform tumors for
      treatment modification schemes. The goal of this study was to systematically
      analyze if immunohistochemical (IHC) assessment of molecular markers, involved in
      treatment resistance, and 18F-FDG PET parameters could accurately distinguish
      separate HNC tumors. METHODS: Several imaging parameters and texture features for
      18F-FDG small-animal PET and immunohistochemical markers related to metabolism,
      hypoxia, proliferation and tumor blood perfusion were assessed within groups of
      BALB/c nu/nu mice xenografted with 14 human HNC models. Classification methods
      were used to predict tumor line based on sets of parameters. RESULTS: We found
      that 18F-FDG PET could not differentiate between the tumor lines. On the
      contrary, combined IHC parameters could accurately allocate individual tumors to
      the correct model. From 9 analyzed IHC parameters, a cluster of 6 random
      parameters already classified 70.3% correctly. Combining all PET/IHC
      characteristics resulted in the highest tumor line classification accuracy
      (81.0%; cross validation 82.0%), which was just 2.2% higher (p = 5.2*10-32) than
      the performance of the IHC parameter/feature based model. CONCLUSIONS: With a
      select set of IHC markers representing cellular processes of metabolism,
      proliferation, hypoxia and perfusion, one can reliably distinguish between HNC
      tumor lines. Addition of 18F-FDG PET improves classification accuracy of IHC to a
      significant yet minor degree. These results may form a basis for development of
      tumor characterization models for treatment allocation purposes.

PMID- 24571593
TI  - Pruritic nodules and plaques on the arms with blisters in a patient with chronic
      lymphocytic leukemia.

PMID- 24571594
TI  - Relaxers damage hair and increase fragility.

PMID- 24571595
TI  - Application of a photogrammetric kinematic model for prediction of lung volumes
      in adolescents: a pilot study.
AB  - BACKGROUND: There are several ways to measure the respiratory system, among them
      inductance plethysmography and three-dimensional kinematic analysis, methods of
      high cost and difficult transportability. The objective of this study was to
      correlate respiratory volumes obtained by spirometry standard equipment with a
      biomechanical model photogrammetric analysis of adolescents. METHODS: We
      evaluated 50 subjects of both genders, aged between 14 and 17 years old,
      excluding those with respiratory obstruction or restriction. Stickers with
      markers, there was a five-point mapping for anatomical modeling and
      photogrammetry, with each evaluated in supine position, was sought to test the
      Forced Vital Capacity (FVC). The test was filmed and repeated three times. Images
      of the films were extracted for the moment of maximum exhalation and inhalation
      of proof with better breathing. With the use of a commercial software, defined
      the respiratory volumes to the thorax and abdomen. RESULTS: The photogrammetric
      analysis has found values strongly correlated with the spirometric measurements
      of FVC (0.812), forced expiratory volume in one second (FEV1 - 0.708), Peak
      Expiratory Flow (PEF - 0.762) in addition to post test performed Inspiration (IP-
      0.816). There was a higher ventilatory mobility for boys than girls for Lower
      Chest and Lower and Upper Abdomen. It was possible to reach a regression R2 =
      0.866 for proof of FVC and R2 = 0.776 for IP with the use of photogrammetry,
      presenting a standard error of 0.353 and 0.451, respectively. CONCLUSIONS:
      Photogrammetry can be used to study thoracoabdominal movements by applying
      analytical two-dimensional and three-dimensional images acquired using a video
      camera being, applicable and reproducible.

PMID- 24571596
TI  - Development of a simple score to predict outcome for unresponsive wakefulness
      syndrome.
AB  - INTRODUCTION: Accurate assessment of prognosis for patients with unresponsive
      wakefulness syndrome (UWS; formerly vegetative state) may help clinicians and
      families guide the type and intensity of therapy; however, there is no suitable
      and accurate means to predict the outcome so far. We aimed to develop a simple
      bedside scoring system to predict the likelihood of awareness recovery in
      patients with UWS. METHODS: We prospectively enrolled 56 patients (age range 10
      to 73 years) with UWS 3 to 12 weeks post-onset. We collected demographic data and
      performed neurological, serological and neurophysiological tests at study entry.
      Each patient received a one year follow-up, during which awareness recovery was
      assessed by experienced physicians on the basis of clinical criteria. Univariate
      and multivariable analyses were employed to assess the relationships between
      predictors and awareness recovery. RESULTS: A total of 56 participants were
      included in the study; of these, 24 patients recovered awareness, 3 with moderate
      disabilities, 8 with severe disabilities, 12 were in a minimally conscious state,
      and 1 died after recovery. During the study, 23 patients remained in UWS and 9
      died in UWS. Motor response, type of brain injury, electroencephalogram
      reactivity, sleep spindles and N20 were shown to be independent predictors for
      awareness recovery. Based on their coefficients in the model, we assigned these
      predictors with 1 point each and created a 5-point score for prediction of
      awareness recovery. The resulting score showed good predictive accuracy in the
      derivation cohort. The area under the receiver operating characteristic curve for
      the score was 0.918 with 87.50% sensitivity. CONCLUSION: This simple bedside
      prognostic score can be used to predict the probability of awareness recovery in
      UWS, thus provide families and clinicians with useful outcome information.

PMID- 24571597
TI  - Temporal leukocyte numbers and granulocyte activation in pulsatile and rotary
      ventricular assist device patients.
AB  - Individual ventricular assist device (VAD) design may affect leukocytes and
      impact immunity. Few studies have presented leukocyte and infection profiles in
      VAD patients over the course of the implant period. CD11b (MAC-1) expression on
      granulocytes is an indicator of activation during inflammation, mediating
      extravasation and the release of reactive oxygen species in tissue. No reported
      studies have presented MAC-1 expression on circulating granulocytes in VAD
      patients. Fifty-six patients implanted at a single center with a HeartMate II
      (HMII; n = 32), HeartWare (HW; n = 12), or Thoratec pneumatic VAD (PVAD; n = 12)
      between 1999 and 2011 were followed for 120 days of support. The leukocyte
      profiles and infectious events of all patients were evaluated; additionally, a
      subset had MAC-1 expression on circulating granulocytes was measured (HMII n = 9;
      HW n = 7; PVAD n = 4). All groups exhibited a significant peak in leukocyte
      numbers at postoperative day (POD) 14 while simultaneously experiencing a
      significant decrease in hematocrit. HMII patients exhibited a 3.2-fold increase
      in granulocyte MAC-1 expression at POD 14, and the temporal trend over the
      implant period differed from that experienced by HW patients. Further, HW
      patients experienced significantly fewer infection events. Alterations in
      leukocyte profiles and granulocyte activation experienced by VAD patients appear
      to be device-specific. Elevations in leukocyte activation may be related to an
      increased risk for infection, although the specific relationship between these
      phenomena in this patient group is not known. 

PMID- 24571598
TI  - Regional molecular and cellular differences in the female rabbit Achilles tendon
      complex: potential implications for understanding responses to loading.
AB  - The aim of this study was: (i) to analyze the morphology and expression of
      extracellular matrix genes in six different regions of the Achilles tendon
      complex of intact normal rabbits; and (ii) to assess the effect of
      ovariohysterectomy (OVH) on the regional expression of these genes. Female New
      Zealand White rabbits were separated into two groups: (i) intact normal rabbits
      (n = 4); and (ii) OVH rabbits (n = 8). For each rabbit, the Achilles tendon
      complex was dissected into six regions: distal gastrocnemius (DG); distal flexor
      digitorum superficialis; proximal lateral gastrocnemius (PLG); proximal medial
      gastrocnemius; proximal flexor digitorum superficialis; and paratenon. For each
      of the regions, hematoxylin and eosin staining was performed for histological
      evaluation of intact normal rabbit tissues and mRNA levels for proteoglycans,
      collagens and genes associated with collagen regulation were assessed by real
      time reverse transcription-quantitative polymerase chain reaction for both the
      intact normal and OVH rabbit tissues. The distal regions displayed a more
      fibrocartilaginous phenotype. For intact normal rabbits, aggrecan mRNA expression
      was higher in the distal regions of the Achilles tendon complex compared with the
      proximal regions. Collagen Type I and matrix metalloproteinase-2 expression
      levels were increased in the PLG compared to the DG in the intact normal rabbit
      tissues. The tendons from OVH rabbits had lower gene expressions for the
      proteoglycans aggrecan, biglycan, decorin and versican compared with the intact
      normal rabbits, although the regional differences of increased aggrecan
      expression in distal regions compared with proximal regions persisted. The
      tensile and compressive forces experienced in the examined regions may be related
      to the regional differences found in gene expression. The lower mRNA expression
      of the genes examined in the OVH group confirms a potential effect of systemic
      estrogen on tendon.

PMID- 24571601
TI  - Pulmonary enteric adenocarcinoma indistinguishable morphologically and
      immunohistologically from metastatic colorectal carcinoma.

PMID- 24571599
TI  - The role of Nox2-derived ROS in the development of cognitive impairment after
      sepsis.
AB  - BACKGROUND: Sepsis- associated encephalopathy (SAE) is an early and common
      feature of severe infections. Oxidative stress is one of the mechanisms
      associated with the pathophysiology of SAE. The goal of this study was to
      investigate the involvement of NADPH oxidase in neuroinflammation and in the long
      term cognitive impairment of sepsis survivors. METHODS: Sepsis was induced in WT
      and gp91(phox) knockout mice (gp91(phox-/-)) by cecal ligation and puncture (CLP)
      to induce fecal peritonitis. We measured oxidative stress, Nox2 and Nox4 gene
      expression and neuroinflammation in the hippocampus at six hours, twenty-four
      hours and five days post-sepsis. Mice were also treated with apocynin, a NADPH
      oxidase inhibitor. Behavioral outcomes were evaluated 15 days after sepsis with
      the inhibitory avoidance test and the Morris water maze in control and apocynin
      treated WT mice. RESULTS: Acute oxidative damage to the hippocampus was
      identified by increased 4-HNE expression in parallel with an increase in Nox2
      gene expression after sepsis. Pharmacological inhibition of Nox2 with apocynin
      completely inhibited hippocampal oxidative stress in septic animals.
      Pharmacologic inhibition or the absence of Nox2 in gp91(phox-/-) mice prevented
      glial cell activation, one of the central mechanisms associated with SAE.
      Finally, treatment with apocynin and inhibition of hippocampal oxidative stress
      in the acute phase of sepsis prevented the development of long-term cognitive
      impairment. CONCLUSIONS: Our results demonstrate that Nox2 is the main source of
      reactive oxygen species (ROS) involved in the oxidative damage to the hippocampus
      in SAE and that Nox2-derived ROS are determining factors for cognitive
      impairments after sepsis. These findings highlight the importance of Nox2-derived
      ROS as a central mechanism in the development of neuroinflammation associated
      with SAE.

PMID- 24571600
TI  - Impact of caste on the neurodevelopment of young children from birth to 36 months
      of age: a birth cohort study in Chitwan Valley, Nepal.
AB  - BACKGROUND: Caste, a proxy of socioeconomic position, can influence the
      neurodevelopment of children through several pathways, including exposure to
      toxic elements. Studies from developing countries where caste is represented by
      prevailing caste groups and people are highly exposed to toxic elements can
      provide useful insights into the mechanisms of neurodevelopmental inequities
      among children. This study aims to investigate the impact of caste on the
      neurodevelopment of children from birth to 36 months of age in Chitwan Valley,
      Nepal, where people are exposed to high levels of arsenic (As) and lead (Pb).
      METHODS: Participants (N = 94) were mother-infant pairs from the Chitwan district
      in Nepal. The neurodevelopment of the infants was assessed using the Brazelton
      Neonatal Behavioral Assessment Scale, Third Edition, (NBAS III) at birth and the
      Bayley Scales of Infant Development, Second Edition, (BSID II) at ages 6, 24, and
      36 months. Caste was categorized based on surname, which, in Nepal generally
      refers to one of four caste groups. We also measured the concentrations of As and
      Pb in cord blood. RESULTS: Caste was positively associated with the state
      regulation cluster score of the NBAS III at birth after adjustment for covariates
      (p for trend < 0.01). Adding cord blood As levels attenuated the association (p
      for trend = 0.12). With regard to neurodevelopment at six months of age, the
      third-ranked caste group scored higher than the first-ranked caste group on the
      Mental Development Index (MDI) of the BSID II (coefficient = 3.7; 95% confidence
      interval (CI) = 1.3 to 6.0). This difference remained significant after
      adjustment for cord blood As levels and other covariates was made (coefficient =
      3.9; 95% CI = 1.2 to 6.7). The remaining clusters of the NBAS III and BSID II at
      6, 24, and 36 months were not significantly associated with caste group.
      CONCLUSIONS: Caste was positively associated with the state regulation cluster
      score of NBAS III at birth. This association was partially mediated by cord blood
      As levels. However, the negative impact of caste on neurodevelopment disappeared
      as the children grew. Furthermore, an inverse association between caste and MDI
      at six months of age was observed. Additional studies are needed to elucidate the
      mechanism of how caste affects neurodevelopment.

PMID- 24571602
TI  - Factors contributing to medication errors in Turkey: nurses' perspectives.
AB  - AIM: The aim of this study was to describe the experiences of nurses with regard
      to medication errors. BACKGROUND: Medication errors result in a significant
      proportion of the deaths related to avoidable medical errors in hospitals.
      DESIGN: A descriptive cross-sectional study. METHOD: This study was conducted on
      243 nurses working in two state hospitals in Turkey. Data collection was by means
      of a questionnaire developed by the researchers. Medication errors were explored
      in three areas: types of error, contributing factors and reporting of errors.
      RESULT: Among the most frequent types of errors were administration of drugs not
      ordered by the doctor, administration of a drug prepared by someone else and
      administration of a drug to the wrong patient. Contributing factors for
      medication errors included 'having to write an order in place of the physician',
      and 'an oral request being given in a non-urgent situation'. CONCLUSION: These
      results show the need for a multi-disciplinary approach in the prevention of
      errors. IMPLICATIONS FOR NURSING MANAGEMENT: Hospital administrations should
      maintain adequate staffing levels. Improving medication error reporting is also
      imperative in order to enable nurses to document all errors and potential errors
      as adverse events.

PMID- 24571603
TI  - Auricular acupressure helps improve sleep quality for severe insomnia in
      maintenance hemodialysis patients: a pilot study.
AB  - BACKGROUND: Insomnia is common in patients undergoing maintenance hemodialysis
      (MHD). Long-term use of sedative-hypnotic agents is often correlated with
      increasing adverse effects. Auricular acupressure therapy (AAT) applied to
      specific auricular acupoints for managing insomnia has achieved favorable
      outcomes in a hemodialysis unit. This pilot study was performed to demonstrate
      the potential of AAT for insomnia in MHD patients and to prepare for a future
      randomized controlled trial. METHODS: Eligible patients were enrolled into this
      descriptive pilot study and received AAT designed to manage insomnia for 4 weeks.
      Questionnaires that used the Pittsburgh sleep quality index (PSQI) were completed
      at baseline, after a 4-week intervention, and 1 month after completion of
      treatment. Sleep quality and other clinical characteristics, including sleeping
      pills taken, were statistically compared between different time points. RESULTS:
      A total of 22 patients were selected as eligible participants and completed the
      treatment and questionnaires. The mean global PSQI score was significantly
      decreased after AAT intervention (p<0.05). Participants reported improved sleep
      quality (p<0.01), shorter sleep latency (p<0.05), less sleep disturbance
      (p<0.01), and less daytime dysfunction (p=0.01). They also exhibited less
      dependency on sleep medications, indicated by the reduction in weekly estazolam
      consumption from 6.98+/-4.44 pills to 4.23+/-2.66 pills (p<0.01). However, these
      improvements were not preserved 1 month after treatment. CONCLUSION: In this
      single-center pilot study, complementary AAT for MHD patients with severe
      insomnia was feasible and well tolerated and showed encouraging results for sleep
      quality.

PMID- 24571604
TI  - Identification of a new HLA allele, HLA-B*13:70, in a Chinese individual.
AB  - HLA-B*13:70 differs from HLA-B*13:02:01 by one nucleotide (A to G) at nucleotide
      position 329 in exon 2. 

PMID- 24571605
TI  - Successful treatment for retroperitoneal cavernous hemangioma adjacent to the
      renal hilum via the laparoscopic approach: a case report.
AB  - INTRODUCTION: Cavernous hemangiomas are common benign tumors of the skin or liver
      but can also rarely originate from the retroperitoneal space, especially adjacent
      to the renal hilum. Qualitative characterization of these retroperitoneal tumors
      using available imaging modalities is relatively difficult. CASE PRESENTATION: A
      40-year-old Japanese woman was incidentally noted to have a round homogenous
      tumor adjacent to the left renal hilum on computed tomography. The preoperative
      diagnosis was paraganglioma according to hormonal and clinical findings. The
      tumor was successfully resected via a laparoscopic approach, and
      histopathological examination of the tumor revealed cavernous hemangioma.
      CONCLUSIONS: Cavernous hemangioma is a rare but relatively benign disease when
      considering the different types of retroperitoneal tumors. We were able to
      effectively treat the retroperitoneal cavernous hemangioma via laparoscopy.

PMID- 24571607
TI  - Patterned surface with controllable wettability for inkjet printing of flexible
      printed electronics.
AB  - Appropriate control of substrate surface properties prior to inkjet printing
      could be employed to improve the printing quality of fine resolution structures.
      In this paper, novel methods to fabricate patterned surfaces with a combination
      of hydrophilic and hydrophobic properties are investigated. The results of inkjet
      printing of PEDOT/PSS conductive ink on these modified surfaces are presented.
      Selective wetting was achieved via a two-step hydrophilic-hydrophobic coating of
      3-aminopropyl trimethoxysilane (APTMS) and 3M electronic grade chemical
      respectively on PET surfaces; this was followed by a selective hydrophilic
      treatment (either atmospheric O2/Ar plasma or UV/ozone surface treatment) with
      the aid of a Nickel stencil. Hydrophobic regions with water contact angle (WCA)
      of 105 degrees  and superhydrophilic regions with WCA <5 degrees  can be achieved
      on a single surface. During inkjet printing of the treated surfaces, PEDOT/PSS
      ink spread spontaneously along the hydrophilic areas while avoiding the
      hydrophobic regions. Fine features smaller than the inkjet droplet size
      (approximately 55 MUm in diameter) can be successfully printed on the patterned
      surface with high wettability contrast. 

PMID- 24571606
TI  - Radionuclide transport behavior in a generic geological radioactive waste
      repository.
AB  - We performed numerical simulations of groundwater flow and radionuclide transport
      to study the influence of several factors, including the ambient hydraulic
      gradient, groundwater pressure anomalies, and the properties of the excavation
      damaged zone (EDZ), on the prevailing transport mechanism (i.e., advection or
      molecular diffusion) in a generic nuclear waste repository within a clay-rich
      geological formation. By comparing simulation results, we show that the EDZ plays
      a major role as a preferential flowpath for radionuclide transport. When the EDZ
      is not taken into account, transport is dominated by molecular diffusion in
      almost the totality of the simulated domain, and transport velocity is about 40%
      slower. Modeling results also show that a reduction in hydraulic gradient leads
      to a greater predominance of diffusive transport, slowing down radionuclide
      transport by about 30% with respect to a scenario assuming a unit gradient. In
      addition, inward flow caused by negative pressure anomalies in the clay-rich
      formation further reduces transport velocity, enhancing the ability of the
      geological barrier to contain the radioactive waste. On the other hand, local
      high gradients associated with positive pressure anomalies can speed up
      radionuclide transport with respect to steady-state flow systems having the same
      regional hydraulic gradients. Transport behavior was also found to be sensitive
      to both geometrical and hydrogeological parameters of the EDZ. Results from this
      work can provide useful knowledge toward correctly assessing the post-closure
      safety of a geological disposal system. 

PMID- 24571608
TI  - Optic and auditory pathway dysfunction in demyelinating neuropathies.
AB  - OBJECTIVE: The involvement of optic and auditory pathways has rarely been studied
      in demyelinating polyneuropathies. We here aimed to study this further in a
      cohort of patients with acquired and gentic demyelinating neuropathy. METHODS: We
      studied eight patients with hereditary neuropathy with liability to pressure
      palsies (HNPP), six with Charcot-Marie-Tooth disease type 1A (CMT1A), ten with
      chronic inflammatory demyelinating polyneuropathy (CIDP) and seven with
      antimyelin-associated glycoprotein (MAG) neuropathy using visual evoked
      potentials and brainstem auditory evoked potentials. RESULTS: Optic pathway
      dysfunction was detected in 6/7 anti-MAG neuropathy patients, about half of those
      with CIDP and HNPP, but only in 1/6 patients with CMT1A. Peripheral auditory
      nerve dysfunction appeared common in all groups except HNPP. Brainstem
      involvement was exceptional in all groups. CONCLUSIONS: We conclude optic nerve
      involvement may be frequent in all demyelinating polyneuropathies, particularly
      anti-MAG neuropathy, except in CMT1A. Peripheral auditory nerves may be spared in
      HNPP possibly due to absence of local compression. Evidence for central brainstem
      pathology appeared infrequent in all four studied neuropathies. This study
      suggests that acquired and genetic demyelinating polyneuropathies may be
      associated with optic and auditory nerve involvement, which may contribute to
      neurological disability, and require greater awareness.

PMID- 24571609
TI  - Assessing the significance of global and local correlations under spatial
      autocorrelation: a nonparametric approach.
AB  - We propose a method to test the correlation of two random fields when they are
      both spatially autocorrelated. In this scenario, the assumption of independence
      for the pair of observations in the standard test does not hold, and as a result
      we reject in many cases where there is no effect (the precision of the null
      distribution is overestimated). Our method recovers the null distribution taking
      into account the autocorrelation. It uses Monte-Carlo methods, and focuses on
      permuting, and then smoothing and scaling one of the variables to destroy the
      correlation with the other, while maintaining at the same time the initial
      autocorrelation. With this simulation model, any test based on the independence
      of two (or more) random fields can be constructed. This research was motivated by
      a project in biodiversity and conservation in the Biology Department at Stanford
      University.

PMID- 24571610
TI  - Novel resveratrol-based substrates for human hepatic, renal, and intestinal UDP
      glucuronosyltransferases.
AB  - Trans-Resveratrol (tRes) has been shown to have powerful antioxidant, anti
      inflammatory, anticarcinogenic, and antiaging properties; however, its use as a
      therapeutic agent is limited by its rapid metabolism into its conjugated forms by
      UDP-glucuronosyltransferases (UGTs). The aim of the current study was to test the
      hypothesis that the limited bioavailability of tRes can be improved by modifying
      its structure to create analogs which would be glucuronidated at a lower rate
      than tRes itself. In this work, three synthetic stilbenoids, (E)-3-(3-hydroxy-4
      methoxyphenyl)-2-(3,4,5-trimethoxyphenyl)acrylic acid (NI-12a), (E)-2,4-dimethoxy
      6-(4-methoxystyryl)benzaldehyde oxime (NI-ST-05), and (E)-4-(3,5-dimethoxystyryl)
      2,6-dinitrophenol (DNR-1), have been designed based on the structure of tRes and
      synthesized in our laboratory. UGTs recognize and glucuronidate tRes at each of
      the 3 hydroxyl groups attached to its aromatic rings. Therefore, each of the
      above compounds was designed with the majority of the hydroxyl groups blocked by
      methylation and the addition of other novel functional groups as part of a drug
      optimization program. The activities of recombinant human UGTs from the 1A and 2B
      families were examined for their capacity to metabolize these compounds.
      Glucuronide formation was identified using HPLC and verified by beta
      glucuronidase hydrolysis and LC-MS/MS analysis. NI-12a was glucuronidated at both
      the -COOH and -OH functions, NI-ST-05 formed a novel N-O-glucuronide, and no
      product was observed for DNR-1. NI-12a is primarily metabolized by the hepatic
      and renal enzyme UGT1A9, whereas NI-ST-05 is primarily metabolized by an
      extrahepatic enzyme, UGT1A10, with apparent Km values of 240 and 6.2 MUM,
      respectively. The involvement of hepatic and intestinal UGTs in the metabolism of
      both compounds was further confirmed using a panel of human liver and intestinal
      microsomes, and high individual variation in activity was demonstrated between
      donors. In summary, these studies clearly establish that modified, tRes-based
      stilbenoids may be preferable alternatives to tRes itself due to increased
      bioavailability via altered conjugation.

PMID- 24571611
TI  - Oxygen atom transfer to a half-sandwich iridium complex: clean oxidation yielding
      a molecular product.
AB  - The oxidation of [Ir(Cp*)(phpy)(NCAr(F))][B(Ar(F))4] (1; Cp* = eta(5)
      pentamethylcyclopentadienyl, phpy = 2-phenylene-kappaC(1')-pyridine-kappaN,
      NCAr(F) = 3,5-bis(trifluoromethyl)benzonitrile, B(Ar(F))4 = tetrakis[3,5
      bis(trifluoromethyl)phenyl]borate) with the oxygen atom transfer (OAT) reagent 2
      tert-butylsulfonyliodosobenzene (sPhIO) yielded a single, molecular product at 
      40  degrees C. New Ir(Cp*) complexes with bidentate ligands derived by oxidation
      of phpy were synthesized to model possible products resulting from oxygen atom
      insertion into the iridium-carbon and/or iridium-nitrogen bonds of phpy. These
      new ligands were either cleaved from iridium by water or formed unreactive,
      phenoxide-bridged iridium dimers. The reactivity of these molecules suggested
      possible decomposition pathways of Ir(Cp*)-based water oxidation catalysts with
      bidentate ligands that are susceptible to oxidation. Monitoring the
      [Ir(Cp*)(phpy)(NCAr(F))](+) oxidation reaction by low-temperature NMR techniques
      revealed that the reaction involved two separate OAT events. An intermediate was
      detected, synthesized independently with trapping ligands, and characterized. The
      first oxidation step involves direct attack of the sPhIO oxidant on the carbon of
      the coordinated nitrile ligand. Oxygen atom transfer to carbon, followed by
      insertion into the iridium-carbon bond of phpy, formed a coordinated organic
      amide. A second oxygen atom transfer generated an unidentified iridium species
      (the "oxidized complex"). In the presence of triphenylphosphine, the "oxidized
      complex" proved capable of transferring one oxygen atom to phosphine, generating
      phosphine oxide and forming an Ir-PPh3 adduct in 92% yield. The final Ir-PPh3
      product was fully characterized. 

PMID- 24571612
TI  - Feasibility of a web-based gatekeeper training: implications for suicide
      prevention.
AB  - Web-based training programs have advantages such as increased scheduling
      flexibility and decreased training costs. Yet the feasibility of applying them to
      injury prevention programs such as suicide prevention gatekeeper training has not
      been empirically verified. Two studies were conducted to assess the feasibility
      and effectiveness of a web-based version of the Question, Persuade, and Refer
      (QPR) gatekeeper training program. Results of Study 1 revealed that participants
      in a web-based training demonstrated significant gains in knowledge of suicide
      prevention, self-efficacy for suicide prevention, and behavioral intentions to
      engage in suicide prevention, as compared to those in a control group. Results of
      Study 2 further showed that the web-based training may be as effective as the
      face-to-face QPR training across pre- (T1) and post training (T2); however,
      knowledge, self-efficacy, and behavioral intentions in both groups generally
      declined from T2 to 6-months after the training. Overall, these results provide
      initial evidence to support the feasibility of adopting web-based media to
      deliver gatekeeper training. Moreover, the present findings suggest the need to
      understand how to maintain gatekeepers' knowledge, confidence, motivation, and
      skills after training. 

PMID- 24571614
TI  - How we "breathed life" into problem-based learning cases using a mobile
      application.
AB  - BACKGROUND: Problem-based learning (PBL) has been widely adopted in medical
      education. Learners become bored with paper-based cases as they progress through
      their studies. AIM: To breathe life (i.e. develop virtual patients) into paper
      based PBL cases. METHODS: The "patients" in paper-based PBL cases in one Year 2
      were transformed into virtual patients by simulated patients role-playing and the
      videos and associated patient data uploaded to Bond's Virtual Hospital, a mobile
      Application. In unsupervised "clinical teams", second-year students undertook
      "ward rounds" twice a week, prompted by a virtual consultant and registered
      nurse. Immediately following the "ward rounds", they met with a clinician
      facilitator to discuss their "patients". RESULTS: Apart from some minor technical
      issues, the experience was rated positively by students and clinical
      facilitators. They claimed that it provided students with a sense of what happens
      in the real world of medicine. The group work skills students had developed
      during PBL stood them in good stead to self-manage their "clinical teams".
      CONCLUSIONS: This more authentic PBL experience will be extended to earlier
      semesters as well as later in the curriculum as the virtual hospital can be used
      to expose learners to a profile of patients that may not be guaranteed during
      hospital rounds.

PMID- 24571613
TI  - Increased IR-A/IR-B ratio in non-small cell lung cancers associates with lower
      epithelial-mesenchymal transition signature and longer survival in squamous cell
      lung carcinoma.
AB  - BACKGROUND: To evaluate the insulin receptor isoform mRNA expression status in
      non-small cell lung cancer (NSCLC) patients. METHODS: RNA-seq data from 614 NSCLC
      [355 adenocarcinomas (LUAD) and 259 squamous cell carcinomas (LUSC)] and 92
      normal lung specimens were obtained from The Cancer Genome Atlas (TCGA) to
      evaluate the mRNA expression of insulin receptor isoform A (IR-A) and insulin
      receptor isoform B (IR-B). The differential expression status of the insulin
      receptor isoforms in NSCLC patients was confirmed using qRT-PCR assays with lung
      cancer cDNA arrays and primary tumor samples. RESULTS: The mRNA expression levels
      of IR-B were significantly lower in some NSCLC samples compared to normal lung
      specimens, including both LUAD and LUSC. Notably, no IR-B transcripts were
      detected - only the IR-A isoform was expressed in 11% of NSCLC patients. This
      decrease in IR-B expression contributed to an elevated IR-A/IR-B ratio, which was
      also associated with lower epithelial-mesenchymal transition gene signatures in
      NSCLC and longer patient survival under standard of care in LUSC. In addition to
      NSCLC, RNA-seq data from TCGA revealed a similar increase in IR-A/IR-B ratio in
      many other cancer types, with high prevalence in acute myeloid leukemia,
      glioblastoma multiforme, and brain lower grade glioma. CONCLUSIONS: Our results
      indicate a common reduction of the mRNA expression level of IR-B and an increased
      IR-A/IR-B mRNA ratio in NSCLC and other tumor types. The relationship of altered
      IR-A/IR-B ratios with cancer progression and patient survival should be
      prospectively explored in future studies.

PMID- 24571615
TI  - Endometriosis and RAS system gene polymorphisms: the association of ACE A2350G
      polymorphism with endometriosis in Polish individuals.
AB  - To analyze the polymorphisms of angiotensin I converting enzyme (ACE) gene
      (insertion/deletion [I/D], A2350G) and angiotensin II type 1 receptor gene
      (A1166C) in women with endometriosis and to determine the correlation of the
      identified genotypes with the severity of the disease. Additionally, to estimate
      the prognostic value of the polymorphisms in patients with endometriosis treated
      due to infertility. The study group included 241 women, the control group
      (without endometriosis)-127. The molecular analysis was performed by polymerase
      chain reaction (PCR) and PCR-restriction fragment length polymorphism technique.
      For I/D ACE and A1166C AT1 polymorphisms no significant differences were observed
      between the study and control groups and between the severity grades of the
      disease (p>0.05). For A2350G ACE polymorphism the frequency of genotypes for the
      study and control groups respectively was the following: AA-31.54%, AG-54.36%, GG
      14.11% and AA-55.12%, AG-36.22%, GG-8.66% (x(2)=19.36, p<0.0001). Statistically
      significant differences were found between the frequency of A and G alleles
      between both groups (x(2)=15.16, p=0.0001), but not when individual grades of the
      disease severity were compared. There was no association between the investigated
      polymorphisms and the effect of infertility treatment. A2350G polymorphism
      (allele G, AG genotype) of ACE gene seems to be associated with the development
      of endometriosis. 

PMID- 24571617
TI  - Valley splitting in a silicon quantum device platform.
AB  - By suppressing an undesirable surface Umklapp process, it is possible to resolve
      the two most occupied states (1Gamma and 2Gamma) in a buried two-dimensional
      electron gas (2DEG) in silicon. The 2DEG exists because of an atomically sharp
      profile of phosphorus dopants which have been formed beneath the Si(001) surface
      (a delta-layer). The energy separation, or valley splitting, of the two most
      occupied bands has critical implications for the properties of delta-layer
      derived devices, yet until now, has not been directly measurable. Density
      functional theory (DFT) allows the 2DEG band structure to be calculated, but
      without experimental verification the size of the valley splitting has been
      unclear. Using a combination of direct spectroscopic measurements and DFT we show
      that the measured band structure is in good qualitative agreement with
      calculations and reveal a valley splitting of 132 +/- 5 meV. We also report the
      effective mass and occupation of the 2DEG states and compare the dispersions and
      Fermi surface with DFT. 

PMID- 24571618
TI  - Diversity, resistance and resilience of the bacterial communities at two alpine
      glacier forefields after a reciprocal soil transplantation.
AB  - In this study, we determined the driving key factor determining variability in
      bacterial community structures in soils at two unvegetated alpine glacier
      forefields with different bedrock geology (calcareous and siliceous). We further
      assessed the resistance and resilience capacities of the bacterial communities
      through reciprocal soil transplantations. Sterilized and unsterilized soils were
      incubated locally ('home') or transplanted ('away') for 15 months (July 2011
      October 2012) and sampled regularly during the snow-free seasons. Changes in
      bacterial community structures were determined through fingerprinting of the 16S
      rRNA gene and correlated with several environmental factors. This study
      demonstrates that bacterial community structures at our field sites were shaped
      by distinct mineralogical soil properties. Soil moisture and pH appeared to not
      be the major driving key factors. Calcareous soil was more selective to bacteria,
      thus diversity was higher in siliceous soils as a positive effect of its more
      diverse mineralogical composition. Bacterial community in the calcareous soil
      exhibited stronger resistance to transplantation than the community in the
      siliceous soil. In fact, siliceous soil was more easily invaded by extrinsic
      taxa. Bacterial communities of both soil types were equally resilient at home,
      although different resilience patterns were observed between calcareous and
      siliceous soils incubated away. 

PMID- 24571616
TI  - HIV-1 induces cytoskeletal alterations and Rac1 activation during monocyte-blood
      brain barrier interactions: modulatory role of CCR5.
AB  - BACKGROUND: Most HIV strains that enter the brain are macrophage-tropic and use
      the CCR5 receptor to bind and infect target cells. Because the cytoskeleton is a
      network of protein filaments involved in cellular movement and migration, we
      investigated whether CCR5 and the cytoskeleton are involved in endothelial
      mononuclear phagocytes interactions, adhesion, and HIV-1 infection. RESULTS:
      Using a cytoskeleton phospho-antibody microarray, we showed that after co-culture
      with human brain microvascular endothelial cells (HBMEC), HIV-1 infected
      monocytes increased expression and activation of cytoskeleton-associated
      proteins, including Rac1/cdc42 and cortactin, compared to non-infected monocytes
      co-cultured with HBMEC. Analysis of brain tissues from HIV-1-infected patients
      validated these findings, and showed transcriptional upregulation of Rac1 and
      cortactin, as well as increased activation of Rac1 in brain tissues of HIV-1
      infected humans, compared to seronegative individuals and subjects with HIV-1
      encephalitis. Confocal imaging showed that brain cells expressing phosphorylated
      Rac1 were mostly macrophages and blood vessels. CCR5 antagonists TAK-799 and
      maraviroc prevented HIV-induced upregulation and phosphorylation of cytoskeleton
      associated proteins, prevented HIV-1 infection of macrophages, and diminished
      viral-induced adhesion of monocytes to HBMEC. Ingenuity pathway analysis suggests
      that during monocyte-endothelial interactions, HIV-1 alters protein expression
      and phosphorylation associated with integrin signaling, cellular morphology and
      cell movement, cellular assembly and organization, and post-translational
      modifications in monocytes. CCR5 antagonists prevented these HIV-1-induced
      alterations. CONCLUSIONS: HIV-1 activates cytoskeletal proteins during monocyte
      endothelial interactions and increase transcription and activation of Rac1 in
      brain tissues. In addition to preventing macrophage infection, CCR5 antagonists
      could diminish viral-induced alteration and phosphorylation of cytoskeletal
      proteins, monocyte adhesion to the brain endothelium and viral entry into the
      central nervous system.

PMID- 24571619
TI  - The randomized physiologic assessment of thrombus aspiration in patients with
      acute ST-segment elevation myocardial infarction trial (PATA STEMI): study
      rationale and design.
AB  - INTRODUCTION: Routine thrombus aspiration is proposed to be superior to
      conventional primary percutaneous coronary intervention (PCI) in terms of
      improved myocardial perfusion, in patients with ST-segment elevation acute
      myocardial infarction (STEMI). However, myocardial perfusion after thrombus
      aspiration has not been evaluated by a quantitative, invasive method. We intend
      to determine whether manual thrombus aspiration in the infarct-related coronary
      artery increases myocardial perfusion assessed by index of microcirculatory
      resistance (IMR) compared with conventional primary PCI. STUDY DESIGN: PATA STEMI
      is a single-center, prospective, randomized trial with a planned inclusion of 128
      patients with the first STEMI. Prior to coronary angiography, patients are
      randomly assigned to thrombus aspiration using the Eliminate aspiration catheter
      (Terumo Medical Supply, Japan) or to conventional primary PCI. After completion
      of primary PCI, IMR is determined both in infarct-related artery and in
      noninfarct-related arteries without critical stenoses. The primary end-point is a
      group mean value of IMR after thrombus aspiration compared with conventional
      primary PCI. Secondary end-points are myocardial perfusion grade, resolution of
      ST-segment elevation, enzymatic estimation of infarct size, left ventricular
      remodeling assessed by echocardiographic indices, and major adverse cardiac
      events rate at 1, 6, and 12 months. CONCLUSION: If manual thrombus aspiration
      significantly reduces microcirculatory resistance, thereby improving myocardial
      perfusion, it may become the routine strategy in primary PCI.

PMID- 24571620
TI  - S-EMG signal compression based on domain transformation and spectral shape
      dynamic bit allocation.
AB  - BACKGROUND: Surface electromyographic (S-EMG) signal processing has been emerging
      in the past few years due to its non-invasive assessment of muscle function and
      structure and because of the fast growing rate of digital technology which brings
      about new solutions and applications. Factors such as sampling rate, quantization
      word length, number of channels and experiment duration can lead to a potentially
      large volume of data. Efficient transmission and/or storage of S-EMG signals are
      actually a research issue. That is the aim of this work. METHODS: This paper
      presents an algorithm for the data compression of surface electromyographic (S
      EMG) signals recorded during isometric contractions protocol and during dynamic
      experimental protocols such as the cycling activity. The proposed algorithm is
      based on discrete wavelet transform to proceed spectral decomposition and de
      correlation, on a dynamic bit allocation procedure to code the wavelets
      transformed coefficients, and on an entropy coding to minimize the remaining
      redundancy and to pack all data. The bit allocation scheme is based on
      mathematical decreasing spectral shape models, which indicates a shorter digital
      word length to code high frequency wavelets transformed coefficients. Four bit
      allocation spectral shape methods were implemented and compared: decreasing
      exponential spectral shape, decreasing linear spectral shape, decreasing square
      root spectral shape and rotated hyperbolic tangent spectral shape. RESULTS: The
      proposed method is demonstrated and evaluated for an isometric protocol and for a
      dynamic protocol using a real S-EMG signal data bank. Objective performance
      evaluations metrics are presented. In addition, comparisons with other encoders
      proposed in scientific literature are shown. CONCLUSIONS: The decreasing bit
      allocation shape applied to the quantized wavelet coefficients combined with
      arithmetic coding results is an efficient procedure. The performance comparisons
      of the proposed S-EMG data compression algorithm with the established techniques
      found in scientific literature have shown promising results.

PMID- 24571622
TI  - Size differentiation in Finnish house sparrows follows Bergmann's rule with
      evidence of local adaptation.
AB  - Bergmann's rule predicts that individuals are larger in more poleward populations
      and that this size gradient has an adaptive basis. Hence, phenotypic divergence
      in size traits between populations (PST ) is expected to exceed the level of
      divergence by drift alone (FST ). We measured 16 skeletal traits, body mass and
      wing length in 409 male and 296 female house sparrows Passer domesticus sampled
      in 12 populations throughout Finland, where the species has its northernmost
      European distributional margin. Morphometric differentiation across populations
      (PST ) was compared with differentiation in 13 microsatellites (FST ). We find
      that twelve traits phenotypically diverged more than FST in both sexes, and an
      additional two traits diverged in males. The phenotypic divergence exceeded FST
      in several traits to such a degree that findings were robust also to strong
      between-population environmental effects. Divergence was particularly strong in
      dimensions of the bill, making it a strong candidate for the study of adaptive
      molecular genetic divergence. Divergent traits increased in size in more northern
      populations. We conclude that house sparrows show evidence of an adaptive
      latitudinal size gradient consistent with Bergmann's rule on the modest spatial
      scale of ca. 600 km. 

PMID- 24571623
TI  - A correction on coastal heads for groundwater flow models.
AB  - We introduce a simple correction to coastal heads for constant-density
      groundwater flow models that contain a coastal boundary, based on previous
      analytical solutions for interface flow. The results demonstrate that accurate
      discharge to the sea in confined aquifers can be obtained by direct application
      of Darcy's law (for constant-density flow) if the coastal heads are corrected to
      ((alpha + 1)/alpha)hs  - B/2alpha, in which hs is the mean sea level above the
      aquifer base, B is the aquifer thickness, and alpha is the density factor. For
      unconfined aquifers, the coastal head should be assigned the value
      hs1+alpha/alpha. The accuracy of using these corrections is demonstrated by
      consistency between constant-density Darcy's solution and variable-density flow
      numerical simulations. The errors introduced by adopting two previous approaches
      (i.e., no correction and using the equivalent fresh water head at the middle
      position of the aquifer to represent the hydraulic head at the coastal boundary)
      are evaluated. Sensitivity analysis shows that errors in discharge to the sea
      could be larger than 100% for typical coastal aquifer parameter ranges. The
      location of observation wells relative to the toe is a key factor controlling the
      estimation error, as it determines the relative aquifer length of constant
      density flow relative to variable-density flow. The coastal head correction
      method introduced in this study facilitates the rapid and accurate estimation of
      the fresh water flux from a given hydraulic head measurement and allows for an
      improved representation of the coastal boundary condition in regional constant
      density groundwater flow models. 

PMID- 24571621
TI  - The rise of assertive community interventions in South Africa: a randomized
      control trial assessing the impact of a modified assertive intervention on
      readmission rates; a three year follow-up.
AB  - BACKGROUND: Many countries have over the last few years incorporated mental
      health assertive interventions in an attempt to address the repercussions of
      deinstitutionalization. Recent publications have failed to duplicate the positive
      outcomes reported initially which has cast doubt on the future of these
      interventions. We previously reported on 29 patients from a developing country
      who completed 12 months in an assertive intervention which was a modified version
      of the international assertive community treatment model. We demonstrated
      reduction in readmission rates as well as improvements in social functioning
      compared to patients from the control group. The obvious question was, however,
      if these outcomes could be sustained for longer periods of time. This study aims
      to determine if modified assertive interventions in an under-resourced setting
      can successfully maintain reductions in hospitalizations. METHODS: Patients
      suffering from schizophrenia who met a modified version of Weidens' high
      frequency criteria were randomized into two groups. One group received a modified
      assertive intervention based on the international assertive community treatment
      model. The other group received standard care according to the model of service
      delivery in this region. Data was collected after 36 months, comparing
      readmissions and days spent in hospital. RESULTS: The results demonstrated
      significant differences between the groups. Patients in the intervention group
      had significantly less readmissions (p = 0.007) and spent less days in hospital
      compared to the patients in the control group (p = 0.013). CONCLUSION: Modified
      assertive interventions may be successful in reducing readmissions and days spent
      in hospital in developing countries where standard care services are less
      comprehensive. These interventions can be tailored in such a way to meet service
      needs and still remain affordable and feasible within the context of an under
      resourced setting.

PMID- 24571624
TI  - Minimally invasive left ventricular assist device explantation after cardiac
      recovery: surgical technical considerations.
AB  - The new generation of left ventricular assist devices (LVADs) has enabled
      minimally invasive surgical procedures for implantation. Herein we present two
      alternative approaches for minimally invasive LVAD explantation following cardiac
      recovery, avoiding a sternotomy and improving patient safety. 

PMID- 24571625
TI  - Solvation dynamics and intermittent oscillation of cell membrane: live Chinese
      hamster ovary cell.
AB  - Dynamics of the exofacial thiols (i.e., cell surface thiol containing membrane
      proteins) of a live Chinese hamster ovary (CHO) cell is probed by time-resolved
      confocal microscopy. For this purpose, a fluorescent probe, 7-(diethylamino)-3-(4
      maleimidophenyl)-4-methylcoumarin (CPM) is covalently attached to the exofacial
      thiols. The emission maximum of CPM bound exofacial thiols indicates a highly
      exposed and polar environment. Using CPM, we studied solvation dynamics, for the
      first time, at the membrane of a live cell. The thiol containing membrane
      proteins shows ultraslow response with average solvation time, ?taus? = 475 ps.
      CPM labeled exofacial thiols also show spontaneous, intermittent oscillation in
      fluorescence intensity with a period of 0.5-1.0 s. This is ascribed to
      reversible, intermittent changes in the structure and conformation of the
      membrane proteins. 

PMID- 24571626
TI  - Effect of cargo loading on occupant injury and seat deformation in motor-vehicle
      crashes.
AB  - PURPOSE: NHTSA studied interior loose objects in the 2000-04 NASS-CDS as part of
      rulemaking on cargo retention testing in FMVSS 208. This study extends the
      investigation of cargo and loose interior object loading on occupant injury and
      seat deformation by cargo in motor-vehicles crashes using NASS-CDS data. METHODS:
      1996-2011 NASS-CDS was used to investigate the effects of loose interior objects
      and seat responses on occupant injury in motor vehicle crashes. Crashes were
      grouped by front, side, rear and rollover. Light vehicles were included with
      model year 1994+. NASS-CDS added new variables for cargo loading as an injury
      source and cause for seat deformation in 2007. NASS-CDS electronic cases were
      analyzed for rear occupants with moderate to severe injury (AIS 2+) from loose
      objects and MAIS 4+F injury with cargo deforming seats in frontal crashes.
      RESULTS: There were no AIS 2+ injuries due to cargo loading in the 16 years of
      NASS-CDS, including specific coding from 2007-11 and by case evaluation in
      earlier years. In frontal crashes, loose or other interior objects accounted for
      250 AIS 2+ injuries in drivers, 32 in front passengers and 206 in 2nd row
      occupants. The overall rate of AIS 2+ injury was 1.000% for 2nd row occupants due
      to loose or other interior objects. The individual cases of AIS 2+ injury from
      loose or other interior objects in 2nd row occupants involved 16 occupants with
      44 injuries in frontal crashes. Two cases involved police vehicles and one, an
      ambulance. In two other cases, the loose interior object was a bike placed in the
      3rd row of a station wagon and an unsecured fan in the 2nd row. Each year, there
      were 540 driver seats deformed by cargo, 438 front-passenger seats and 889 in 2nd
      row seats. Most cargo deformation of front seats occurred in frontal crashes.
      Annually, there were 462 driver seats deformed by cargo in frontal crashes, 143
      front-passenger seats and 660 in 2nd row seats. CONCLUSIONS: This analysis
      supports NHTSA's earlier conclusion that cargo is not a major source of injury in
      frontal crashes. While anecdotal cases have been presented in the literature,
      there were no cases in NASS-CDS. NASS-CDS also showed that when untethered cargo
      deforms rear seats, it was not related to severe injury to 2nd row occupants.

PMID- 24571628
TI  - Incidence of amyotrophic lateral sclerosis in Rhineland-Palatinate, Germany.
AB  - There is a lack of prospective and population based epidemiological data on
      amyotrophic lateral sclerosis in Germany to date. The ALS registry Rhineland
      Palatinate was established to investigate the incidence, course and phenotypic
      variety of ALS in this south-west German state of about 4 million inhabitants.
      During the period 2010-2011, consecutive incident patients with amyotrophic
      lateral sclerosis according to the revised El Escorial criteria were included and
      followed up using multiple overlapping sources of case ascertainment. One hundred
      and forty-six patients were enrolled. The annual crude incidence for amyotrophic
      lateral sclerosis in Rhineland-Palatinate was 1.8/100,000 person-years (95% CI
      1.6-2.2). Male to female ratio was 1.1:1. Incidence increased with age reaching a
      peak in the 70-74 years age group and declined thereafter. Late-onset ALS (>= 75
      years) was found in 14.4% of patients. About 32% of patients presented with
      bulbar onset. In conclusion, incidence rate of amyotrophic lateral sclerosis in
      Rhineland-Palatinate is within the range of other prospective population based
      registers in Europe and North America. Gender ratio is nearly balanced.

PMID- 24571629
TI  - Fluorescent drug-loaded, polymeric-based, branched gold nanoshells for localized
      multimodal therapy and imaging of tumoral cells.
AB  - Here we report the synthesis of PLGA/DOXO-core Au-branched shell nanostructures
      (BGNSHs) functionalized with a human serum albumin/indocyanine green/folic acid
      complex (HSA-ICG-FA) to configure a multifunctional nanotheranostic platform.
      First, branched gold nanoshells (BGNSHs) were obtained through a seeded-growth
      surfactant-less method. These BGNSHs were loaded during the synthetic process
      with the chemotherapeutic drug doxorubicin, a DNA intercalating agent and
      topoisomerase II inhibitior. In parallel, the fluorescent near-infrared (NIR) dye
      indocyanine green (ICG) was conjugated to the protein human serum albumin (HSA)
      by electrostatic and hydrophobic interactions. Subsequently, folic acid was
      covalently attached to the HSA-ICG complex. In this way, we created a protein
      complex with targeting specificity and fluorescent imaging capability. The
      resulting HSA-ICG-FA complex was adsorbed to the gold nanostructures surface
      (BGNSH-HSA-ICG-FA) in a straightforward incubation process thanks to the high
      affinity of HSA to gold surface. In this manner, BGNSH-HSA-ICG-FA platforms were
      featured with multifunctional abilities: the possibility of fluorescence imaging
      for diagnosis and therapy monitoring by exploiting the inherent fluorescence of
      the dye, and a multimodal therapy approach consisting of the simultaneous
      combination of chemotherapy, provided by the loaded drug, and the potential
      cytotoxic effect of photodynamic and photothermal therapies provided by the dye
      and the gold nanolayer of the hybrid structure, respectively, upon NIR light
      irradiation of suitable wavelength. The combination of this trimodal approach was
      observed to exert a synergistic effect on the cytotoxicity of tumoral cells in
      vitro. Furthermore, FA was proved to enhance the internalization of nanoplatform.
      The ability of the nanoplatforms as fluorescence imaging contrast agents was
      tested by preliminary analyzing their biodistribution in vivo in a tumor-bearing
      mice model. 

PMID- 24571630
TI  - Iatrogenic hypervitaminosis D as an unusual cause of persistent vomiting: a case
      report.
AB  - INTRODUCTION: Vitamin D is increasingly recognized to have several beneficial
      effects. Vitamin D deficiency is widely prevalent. Physicians often treat
      patients with high doses of vitamin D for various ailments without any monitoring
      for adverse effects and the prescribed doses often far exceed requirements
      resulting in toxicity. We present here a classic case of iatrogenic
      hypervitaminosis D, which presented with persistent vomiting and acute renal
      failure. CASE PRESENTATION: Here we present a case of a 45-year-old Asian Indian
      woman who presented to us with persistent vomiting the cause of which was
      iatrogenic hypervitaminosis D. She was treated with intravenous fluid, diuretics
      and calcitonin and had clinical improvement. CONCLUSIONS: We suggest that in any
      patient presenting with persistent vomiting and hypercalcemia, particularly in
      the presence of normal parathyroid hormone, a diagnosis of overdose of vitamin D
      should be suspected. Its treatment not only alleviates symptoms but also prevents
      ongoing acute kidney injury.

PMID- 24571627
TI  - Early mobilization of patients receiving extracorporeal membrane oxygenation: a
      retrospective cohort study.
AB  - INTRODUCTION: Critical illness is a well-recognized cause of neuromuscular
      weakness and impaired physical functioning. Physical therapy (PT) has been
      demonstrated to be safe and effective for critically ill patients. The impact of
      such an intervention on patients receiving extracorporeal membrane oxygenation
      (ECMO) has not been well characterized. We describe the feasibility and impact of
      active PT on ECMO patients. METHODS: We performed a retrospective cohort study of
      100 consecutive patients receiving ECMO in the medical intensive care unit of a
      university hospital. RESULTS: Of the 100 patients receiving ECMO, 35 (35%)
      participated in active PT; 19 as bridge to transplant and 16 as bridge to
      recovery. Duration of ECMO was 14.3 +/- 10.9 days. Patients received 7.2 +/- 6.5
      PT sessions while on ECMO. During PT sessions, 18 patients (51%) ambulated
      (median distance 175 feet, range 4 to 2,800) and 9 patients were on vasopressors.
      Whilst receiving ECMO, 23 patients were liberated from invasive mechanical
      ventilation. Of the 16 bridge to recovery patients, 14 (88%) survived to
      discharge; 10 bridge to transplant patients (53%) survived to transplantation,
      with 9 (90%) surviving to discharge. Of the 23 survivors, 13 (57%) went directly
      home, 8 (35%) went to acute rehabilitation, and 2 (9%) went to subacute
      rehabilitation. There were no PT-related complications. CONCLUSIONS: Active PT,
      including ambulation, can be achieved safely and reliably in ECMO patients when
      an experienced, multidisciplinary team is utilized. More research is needed to
      define the barriers to PT and the impact on survival and long-term functional,
      neurocognitive outcomes in this population.

PMID- 24571631
TI  - Description of the novel HLA-DPB1*166:01 allele identified by sequence-based
      typing.
AB  - The novel HLA-DPB1*166:01 allele differs from the closest allele DPB1*152:01 by a
      single missense mutation at CDS nt 315G>A in exon 2. 

PMID- 24571632
TI  - Emulsifying and emulsion-stabilizing properties of gluten hydrolysates.
AB  - Gluten is produced as a coproduct of the wheat starch isolation process. In this
      study, gluten was hydrolyzed to degrees of hydrolysis (DH) of 3-6-10 and 1-2-3
      with alcalase and trypsin, respectively. These peptidases have a clearly distinct
      substrate specificity. Corn oil-in-water emulsions (10 wt % oil) were prepared by
      high-pressure homogenization at pH 7.5. Gluten peptides with DH 3 proved to be
      the most effective in producing peptides displaying emulsifying properties.
      Higher levels of alcalase hydrolysates (2.0 wt %) than of trypsin hydrolysates
      (1.0 wt %) were required to produce stable emulsions with small droplet sizes,
      which is attributed to differences in the nature of the peptides formed. The
      emulsions had small mean droplet diameters (d32 < 1000 nm). Emulsions produced
      with trypsin hydrolysates (stable after 9 days at 55  degrees C) displayed better
      thermal stability compared to those produced with alcalase hydrolysates
      (destabilized after 2 days at 37  degrees C). The hydrolysate-containing
      emulsions, however, were quickly destabilized by salt addition (<=100 mM NaCl)
      and when the pH approached the isoelectric point of the coated droplets (pH
      ~5.5). Microscopic analysis revealed the formation of air-in-oil-in-water
      emulsions at lower hydrolysate concentrations, whereas at higher concentrations
      (>=3.0 wt %) extensive flocculation occurred. Both phenomena contributed to
      creaming of the emulsions. These results may be useful for the utilization of
      gluten hydrolysates in food and beverage products.

PMID- 24571633
TI  - Conscientious objection and its impact on abortion service provision in South
      Africa: a qualitative study.
AB  - BACKGROUND: Despite abortion being legally available in South Africa after a
      change in legislation in 1996, barriers to accessing safe abortion services
      continue to exist. These barriers include provider opposition to abortion often
      on the grounds of religious or moral beliefs including the unregulated practice
      of conscientious objection. Few studies have explored how providers in South
      Africa make sense of, or understand, conscientious objection in terms of refusing
      to provide abortion care services and the consequent impact on abortion access.
      METHODS: A qualitative approach was used which included 48 in-depth interviews
      with a purposively selected population of abortion related health service
      providers, managers and policy influentials in the Western Cape Province, South
      Africa. Data were analyzed using a thematic analysis approach. RESULTS: The ways
      in which conscientious objection was interpreted and practiced, and its impact on
      abortion service provision was explored. In most public sector facilities there
      was a general lack of understanding concerning the circumstances in which health
      care providers were entitled to invoke their right to refuse to provide, or
      assist in abortion services. Providers seemed to have poor understandings of how
      conscientious objection was to be implemented, but were also constrained in that
      there were few guidelines or systems in place to guide them in the process.
      CONCLUSIONS: Exploring the ways in which conscientious objection was interpreted
      and applied by differing levels of health care workers in relation to abortion
      provision raised multiple and contradictory issues. From providers' accounts it
      was often difficult to distinguish what constituted confusion with regards to the
      specifics of how conscientious objection was to be implemented in terms of the
      Choice on Termination of Pregnancy Act, and what was refusal of abortion care
      based on opposition to abortion in general. In order to disentangle what is
      resistance to abortion provision in general, and what is conscientious objection
      on religious or moral grounds, clear guidelines need to be provided including
      what measures need to be undertaken in order to lodge one's right to
      conscientious objection. This would facilitate long term contingency plans for
      overall abortion service provision.

PMID- 24571634
TI  - Semiparametric analysis of incomplete current status outcome data under
      transformation models.
AB  - This work, motivated by an osteoporosis survey study, considers regression
      analysis with incompletely observed current status data. Here the current status
      data, including an examination time and an indicator for whether or not the event
      of interest has occurred by the examination time, is not observed for all
      subjects. Instead, a surrogate outcome subject to misclassification of the
      current status is available for all subjects. We focus on semiparametric
      regression under transformation models, including the proportional hazards and
      proportional odds models as special cases. Under the missing at random mechanism
      where the missingness of the current status outcome can depend only on the
      observed surrogate outcome and covariates, we propose an approach of validation
      likelihood based on the likelihood from the validation subsample where the data
      are fully observed, with adjustments of the probability of observing the current
      status outcome, as well as the distribution of the surrogate outcome in the
      validation subsample. We propose an efficient computation algorithm for
      implementation, and derive consistency and asymptotic normality for inference
      with the proposed estimator. The application to the osteoporosis survey data and
      simulations reveal that the validation likelihood performs well; it removes the
      bias from the "complete case" analysis discarding subjects with missing data, and
      achieves higher efficiency than the inverse probability weighting analysis.

PMID- 24571635
TI  - Work engagement among Dutch dental hygienists.
AB  - OBJECTIVES: The aim of this study was to investigate the level of work engagement
      among Dutch dental hygienists. METHODS: A total of 1,520 questionnaires were
      randomly distributed to the members of the Dutch Dental Hygienists' Association
      (Nederlandse Vereniging van Mondhygienisten). The questionnaire consisted of the
      short form Utrecht Work Engagement Scale, a hypothesized three-factor structure
      of work engagement (Vigor, Dedication, and Absorption). Participants ranked
      statements about how they felt at work on 7-point rating scales (0 = never to 6 =
      always). RESULTS: From a sample of 490 dental hygienists (32 percent) with a mean
      age of 38.2 years [standard deviation (SD) = 10.1], the mean level of work
      engagement was 4.77 (SD = 0.90). The mean score on the dimension of Vigor was
      4.74 (SD = 0.74), Dedication was 5.08 (SD = 0.89), and Absorption was 4.48 (SD =
      1.12). A significant correlation was found between the dimension Absorption and
      age (r = -0.11, P < 0.05). CONCLUSIONS: Dutch dental hygienists reported a very
      high level of work engagement. Many dental hygienists experienced high levels of
      well-being at work at least once a week, with some reporting high levels of well
      being on a daily basis. Only a small percentage of dental hygienists reported
      experiencing very low levels of well-being at work. Dental hygienists also
      reported significantly higher scores for work engagement and the three dimensions
      as compared with the manual norms based on a variety of professions. Finally,
      dental hygienists had higher scores on these questionnaires compared with Dutch
      dentists.

PMID- 24571636
TI  - Reliability and validation of the Hebrew Version of the Reasons for Attempting
      Suicide Questionnaire (RASQ-H) and its importance for mental pain.
AB  - This study evaluated the Hebrew Reasons for Attempting Suicide Questionnaire
      (RASQ-H) and its application for suicidality, and mental pain and its tolerance.
      The sample comprised 97 participants who were inpatient suicide attempters,
      inpatient nonattempters, or nonpatient controls. Differentiation of the RASQ into
      internal perturbation-based reasons and extrapunitive/manipulative motivations
      factors was confirmed, with each scale demonstrating strong internal reliability.
      While the internal perturbation-based reasons factor related positively to some
      suicidal manifestations, to mental pain, and to lower mental pain tolerance, the
      extrapunitive/manipulative motivations factor mostly associated with lower
      suicidality and had fewer and smaller associations with mental pain and its
      tolerance. 

PMID- 24571637
TI  - Probing the spin states of a single acceptor atom.
AB  - We demonstrate a single-hole transistor using an individual acceptor dopant
      embedded in a silicon channel. Magneto-transport spectroscopy reveals that the
      ground state splits as a function of magnetic field into four states, which is
      unique for a single hole bound to an acceptor in a bulk semiconductor. The two
      lowest spin states are heavy (|m(j)| = 3/2) and light (|m(j)| = 1/2) hole-like, a
      two-level system that can be electrically driven and is characterized by a
      magnetic field dependent and long relaxation time, which are properties of
      interest for qubits. Although the bulklike spin splitting of a boron atom is
      preserved in our nanotransistor, the measured Lande g-factors, |g(hh)| = 0.81 +/-
      0.06 and |g(lh)| = 0.85 +/- 0.21 for heavy and light holes respectively, are
      lower than the bulk value.

PMID- 24571638
TI  - In situ preparation of 1D Co@C composite nanorods as negative materials for
      alkaline secondary batteries.
AB  - Cobalt-based coordination compounds were successfully prepared via employing
      nitrilotriacetic acid (NTA) as a complexing agent through a mild surfactant-free
      solvothermal process. Cobalt ions are linked with the amino group or carboxyl
      groups of NTA to become one-dimensional nanorods that can be proved by Fourier
      transform infrared measurement findings. The morphologies of the precursor Co-NTA
      highly depend on the solvent composition, the reaction time and temperature. The
      probable growth mechanism has been proposed. After heat treatment, the Co-NTA
      precursor can be completely converted into Co@C nanorods assembled by numerous
      core-shell-like Co@C nanoparticles, which preserved the rodlike morphology. The
      as-prepared Co@C composites display a rodlike morphology with 4 MUm length and
      100 nm diameter. The electrochemical performances of this novel Co@C material as
      the alkaline secondary Ni/Co battery negative electrode have been systematically
      researched. The discharge capacity of the Co@C-1 composite electrode can attain
      609 mAh g(-1) and retains about 383.3 mAh g(-1) after 120 cycles (the discharge
      current density of 500 mA g(-1)). The novel material exhibits a high discharge
      capacity of 610 and 470 mAh g(-1) at discharge currents of 100 and 1000 mA g(-1),
      respectively. This suggests that approximately 77% of the discharge capacity is
      kept when the discharge current density is increased to 1000 mA g(-1) (10 times
      the initial current density of 100 mA g(-1)). The excellent electrochemical
      properties could be ascribed to the porous channels of the novel Co@C materials,
      which is beneficial to electrolyte diffusion and electrons and ions
      transportation. 

PMID- 24571639
TI  - A spatially filtered multilevel model to account for spatial dependency:
      application to self-rated health status in South Korea.
AB  - BACKGROUND: This study aims to suggest an approach that integrates multilevel
      models and eigenvector spatial filtering methods and apply it to a case study of
      self-rated health status in South Korea. In many previous health-related studies,
      multilevel models and single-level spatial regression are used separately.
      However, the two methods should be used in conjunction because the objectives of
      both approaches are important in health-related analyses. The multilevel model
      enables the simultaneous analysis of both individual and neighborhood factors
      influencing health outcomes. However, the results of conventional multilevel
      models are potentially misleading when spatial dependency across neighborhoods
      exists. Spatial dependency in health-related data indicates that health outcomes
      in nearby neighborhoods are more similar to each other than those in distant
      neighborhoods. Spatial regression models can address this problem by modeling
      spatial dependency. This study explores the possibility of integrating a
      multilevel model and eigenvector spatial filtering, an advanced spatial
      regression for addressing spatial dependency in datasets. METHODS: In this
      spatially filtered multilevel model, eigenvectors function as additional
      explanatory variables accounting for unexplained spatial dependency within the
      neighborhood-level error. The specification addresses the inability of
      conventional multilevel models to account for spatial dependency, and thereby,
      generates more robust outputs. RESULTS: The findings show that sex, employment
      status, monthly household income, and perceived levels of stress are
      significantly associated with self-rated health status. Residents living in
      neighborhoods with low deprivation and a high doctor-to-resident ratio tend to
      report higher health status. The spatially filtered multilevel model provides
      unbiased estimations and improves the explanatory power of the model compared to
      conventional multilevel models although there are no changes in the signs of
      parameters and the significance levels between the two models in this case study.
      CONCLUSIONS: The integrated approach proposed in this paper is a useful tool for
      understanding the geographical distribution of self-rated health status within a
      multilevel framework. In future research, it would be useful to apply the
      spatially filtered multilevel model to other datasets in order to clarify the
      differences between the two models. It is anticipated that this integrated method
      will also out-perform conventional models when it is used in other contexts.

PMID- 24571641
TI  - Incidence rates of sickness absence related to mental disorders: a systematic
      literature review.
AB  - BACKGROUND: Over the past decade, growing attention has been given to the mental
      health of workers. One way to examine the mental health of workers is to look at
      the incidence rates of mental illness-related sickness absence. There is a
      scarcity of literature in which the incidence rates of mental illness-related
      sickness absence among different countries have been considered together. The
      purpose of this systematic literature review is to address the question: Are
      there similarities and differences in the incidence rates of mental disorder
      related sickness absence among and within OECD identified Social Democratic,
      Liberal and Latin American country categories? In this paper, we seek to identify
      differences and similarities in the literature rather than to explain them. With
      this review, we lay the groundwork for and point to areas for future research as
      well as to raise questions regarding reasons for the differences and
      similarities. METHODS: A systematic literature search of the following databases
      were performed: Medline Current, Medline In-process, PsycINFO, Econlit and Web of
      Science. The search period covered 2002-2013. The systematic literature search
      focused on working adults between 18-65 years old who had not retired and who had
      mental and/or substance abuse disorders. Intervention studies were excluded. The
      search focused on medically certified sickness absences. RESULTS: A total of
      3,818 unique citations were identified. Of these, 10 studies met the
      inclusion/exclusion criteria; six were from Social Democratic countries. Their
      quality ranged from good to excellent. There was variation in the incidence rates
      reported by the studies from the Social Democratic, Liberal and Latin American
      countries in this review. CONCLUSIONS: The results of this systematic review
      suggest that this is an emerging area of inquiry that needs to continue to grow.
      Priority areas to support growth include cross jurisdictional collaboration and
      development of a typology characterizing the benefit generosity and work
      integration policies of sickness absence schemes. Finally, the literature should
      be updated to reflect changes in sickness absence benefit schemes over time.

PMID- 24571642
TI  - Compilation and review of 87Sr/86Sr and stable isotopes from groundwater, calcite
      fracture fillings, mineral, and whole-rock sampling at Aspo, Sweden.
AB  - Integrated isotopic and hydrochemical studies of groundwater at Aspo, Sweden,
      support mixing models involving deep saline water, low-solute infiltration, and
      Baltic Sea water. Carbon, oxygen, and strontium isotope analyses of calcite
      fracture fillings indicate that paleohydrologic conditions were different than
      those of today in terms of the isotopic composition of water flowing through
      fractures. Sr isotopes of whole-rock and mineral (plagioclase, microcline,
      biotite, and epidote) samples are used to assess the effects of water-rock
      interaction. Biotite is a major reactant in the early stages of water-rock
      interaction. Strontium isotope systematics of groundwater from deep in the Hard
      Rock Laboratory, and underground research facility, and from low conductivity
      zones revealed a first order mixing line defined by a high-chloride saline
      component with 66 mg/L Sr and an ancient sea water component with approximately
      4.5 mg/L. Dilution with low salinity recharge has produced groundwater with
      variable Sr contents and 87Sr/86Sr values between 0.7186 and 0.7160. Differences
      between Aspo and Laxemar groundwater are shown by trends in Sr concentrations
      plotted against 87Sr/86Sr. The Aspo trend shows increasing 87Sr/86Sr values with
      increasing concentrations of Sr, whereas the Laxemar groundwater trend shows
      little variability in 87Sr/86Sr with increasing Sr concentrations. These trends
      are controlled by the differences in 87Sr/86Sr composition of the saline end
      members in the two areas.

PMID- 24571640
TI  - In situ visualization of newly synthesized proteins in environmental microbes
      using amino acid tagging and click chemistry.
AB  - Here we describe the application of a new click chemistry method for fluorescent
      tracking of protein synthesis in individual microorganisms within environmental
      samples. This technique, termed bioorthogonal non-canonical amino acid tagging
      (BONCAT), is based on the in vivo incorporation of the non-canonical amino acid L
      azidohomoalanine (AHA), a surrogate for l-methionine, followed by fluorescent
      labelling of AHA-containing cellular proteins by azide-alkyne click chemistry.
      BONCAT was evaluated with a range of phylogenetically and physiologically diverse
      archaeal and bacterial pure cultures and enrichments, and used to visualize
      translationally active cells within complex environmental samples including an
      oral biofilm, freshwater and anoxic sediment. We also developed combined assays
      that couple BONCAT with ribosomal RNA (rRNA)-targeted fluorescence in situ
      hybridization (FISH), enabling a direct link between taxonomic identity and
      translational activity. Using a methanotrophic enrichment culture incubated under
      different conditions, we demonstrate the potential of BONCAT-FISH to study
      microbial physiology in situ. A direct comparison of anabolic activity using
      BONCAT and stable isotope labelling by nano-scale secondary ion mass spectrometry
      ((15)NH(3) assimilation) for individual cells within a sediment-sourced
      enrichment culture showed concordance between AHA-positive cells and (15)N
      enrichment. BONCAT-FISH offers a fast, inexpensive and straightforward
      fluorescence microscopy method for studying the in situ activity of environmental
      microbes on a single-cell level.

PMID- 24571644
TI  - Routine serum C-reactive protein and stroke outcome after intravenous
      thrombolysis.
AB  - OBJECTIVES: The clinical usefulness of blood biomarkers in acute stroke is not
      yet fully established, especially after thrombolytic therapy. Our aim was to
      investigate the association between routine serum C-reactive protein (CRP)
      measured within 24 h after admission and outcome in ischaemic stroke patients
      treated with intravenous thrombolysis, adjusting for a history of recent
      infection. METHODS: We analysed the data of consecutive stroke patients who
      received intravenous alteplase in our centre between October 2003 and December
      2011, collected in a detailed prospective registry. Routine serum CRP was
      measured within 24 h from admission; concentration >5 ng/ml was considered
      elevated. RESULTS: Serum CRP was measured in 341 of 406 stroke patients treated
      with alteplase. Patients with elevated CRP (135/341, 42.5%) compared to those
      with normal CRP values, were significantly older, more frequently presented with
      a preexisting disability, comorbidities and suffered more severe strokes. They
      had a higher proportion of symptomatic intracranial haemorrhage according to
      ECASS II definition (7.2% vs 1.6%, P = 0.010), higher 3-month mortality (25.6% vs
      11.3%, P = 0.001), and were less frequently alive and independent after 3 months
      (45.9% vs 63.7%, P = 0.002). However, those associations were not confirmed after
      adjustment for age, stroke severity, diabetes, congestive heart failure, lack of
      prestroke disability and signs of recent infection. CONCLUSIONS: According to our
      findings, elevated routine serum CRP measured within 24 h after admission does
      not seem to independently affect the outcome in patients receiving intravenous
      thrombolysis for stroke. However, further studies of blood samples taken directly
      before the treatment are needed.

PMID- 24571645
TI  - Comparison of two case-based learning conditions with real patients in teaching
      occupational medicine.
AB  - OBJECTIVE: To investigate the impact of three different training formats in
      occupational medicine (OM) on perceptions and performance of undergraduate
      students. METHODS: A comparative study which included all fourth-year medical
      students was conducted over a three-year period. The year group in 2010 (211
      students) received paper case studies followed by one small group session. The
      format used in 2011 actively engaged 188 students in the learning process by
      adding collaborative work and group discussions to the written information. In
      2012, the approach comprised no longer constructed text cases but 212 students
      encountered real patients. Students' perceptions were obtained by questionnaire.
      Their learning performance was assessed through review of written reports and
      score on oral presentations. Statistical differences in ratings were analyzed
      using Fisher's exact and Kruskal-Wallis tests. RESULTS: All three formats were
      found to equally achieve the stated learning objectives. The year groups with
      incorporation of active learning strategies and patient contacts had significant
      better test performance compared to those receiving only written case studies.
      Real patient students gave statistically significant higher rates for relevance,
      authenticity and appropriate difficulty level of the training than did students
      who discussed written case studies. CONCLUSION: Both approaches with augmented
      interaction in 2011 and 2012, improved performance and satisfaction among
      students. However, students valued the use of real patients higher than paper
      form cases.

PMID- 24571643
TI  - Minimal model of self-assembly: emergence of diversity and complexity.
AB  - Molecular self-assembly is ubiquitous in nature, yet prediction of assembly
      pathways from fundamental interparticle interactions has yet to be achieved.
      Here, we introduce a minimal self-assembly model with two attractive and two
      repulsive beads bound into a tetrahedron. The model is associated with a single
      parameter eta defined as the repulsive to attractive interaction ratio. We
      explore self-assembly pathways and resulting assembly morphologies for different
      eta values by discrete molecular dynamics. Our results demonstrate that eta
      governs the assembly dynamics and resulting assembly morphologies, revealing an
      unexpected diversity and complexity for 0.5 <= eta < 1. One of the key processes
      that governs the assembly dynamics is assembly breakage, which emerges
      spontaneously at eta > 0 with the breakage rate increasing with eta. The observed
      assembly pathways display a broad variety of assembly structures characteristic
      of aggregation of amyloidogenic proteins, including quasi-spherical oligomers
      that coassemble into elongated protofibrils, followed by a conversion into
      ordered polymorphic fibril-like aggregates. We further demonstrate that eta can
      be meaningfully mapped onto amyloidogenic protein sequences, with the majority of
      amyloidogenic proteins characterized by 0.5 <= eta < 1. Prion proteins, which are
      known to form highly breakage-prone fibrils, are characterized by eta > 1,
      consistent with the model predictions. Our model thus provides a theoretical
      basis for understanding the universal aspects of aggregation pathways of
      amyloidogenic proteins relevant to human disease. As the model is not specific to
      proteins, these findings represent an important step toward understanding and
      predicting assembly dynamics of not only proteins but also viruses, colloids, and
      nanoparticles. 

PMID- 24571646
TI  - Microwave-assisted preparation of azachalcones and their N-alkyl derivatives with
      antimicrobial activities.
AB  - Two new azachalcones were prepared by both Claisen-Schmidt condensation and a
      simple environmentally trendy microwave-assisted method. Ten new N-alkyl
      (C6,8,10,12,14)-substituted azachalconium bromides (3a-e, 4a-e) were prepared
      from compounds 1 and 2 with corresponding alkyl halides. The antimicrobial
      activities of all the compounds were tested against Enterococcus faecalis,
      Yersinia pseudotuberculosis, Pseudomonas aeruginosa, Escherichia coli and
      Staphylococcus aureus micro-organisms. 

PMID- 24571647
TI  - Plasma level of LDL-cholesterol at diagnosis is a predictor factor of breast
      tumor progression.
AB  - BACKGROUND: Among women, breast cancer (BC) is the leading cancer and the most
      common cause of cancer-related death between 30 and 69 years. Although lifestyle
      and diet are considered to have a role in global BC incidence pattern, the
      specific influence of dyslipidemia in BC onset and progression is not yet
      completely understood. METHODS: Fasting lipid profile (total cholesterol, LDL-C,
      HDL-C, and triglycerides) was prospectively assessed in 244 women with BC who
      were enrolled according to pre-set inclusion criteria: diagnosis of non
      hereditary invasive ductal carcinoma; selection for surgery as first treatment,
      and no history of treatment with lipid-lowering or anti-diabetic drugs in the
      previous year. Pathological and clinical follow-up data were recorded for further
      inclusion in the statistical analysis. RESULTS: Univariate associations show that
      BC patients with higher levels of LDL-C at diagnosis have tumors that are larger,
      with higher differentiation grade, higher proliferative rate (assessed by Ki67
      immunostaining), are more frequently Her2-neu positive and are diagnosed in more
      advanced stages. Cox regression model for disease-free survival (DFS), adjusted
      to tumor T and N stages of TNM classification, and immunohistochemical subtypes,
      revealed that high LDL-C at diagnosis is associated with poor DFS. At 25 months
      of follow up, DFS is 12% higher in BC patients within the third LDL-C tertile
      compared to those in the first tertile. CONCLUSIONS: This is a prospective study
      where LDL-C levels, at diagnosis, emerge as a prognostic factor; and this
      parameter can be useful in the identification and follow-up of high-risk groups.
      Our results further support a possible role for systemic cholesterol in BC
      progression and show that cholesterol metabolism may be an important therapeutic
      target in BC patients.

PMID- 24571649
TI  - Early regenerative response in the intrathoracic porcine esophagus-the impact of
      the inflammation.
AB  - In order to improve the treatment of children born with long-gap esophageal
      atresia, a porcine model was developed for studying esophageal regrowth using a
      bridging graft composed of a silicone stented Biodesign mesh. The aim of the
      study was to investigate how leakage and contact between the native muscle and
      Biodesign mesh affected the early healing response. Resection of 3 cm of
      intrathoracic esophagus was performed in 10 newly weaned piglets. They were fed
      through a gastrostomy 8-10 days prior to sacrifice. In order to achieve
      nonleaking anastomoses, the silicone stent and suturing technique had to be
      adjusted between the first four and second six piglets. The technical adjustment
      decreased leakage. A nonleaking anastomosis could not be achieved when the native
      muscle layers were sewn less central on the bridging graft compared with the
      mucosa. If there was leakage, the inflammatory response increased, with islets of
      perivascular T-lymphocytes and infiltration of macrophages in the native muscle
      layers. In the bridging area, new vessels were seen in the submucosa in 9 of 10
      piglets between 4 and 10 days after surgery. Smooth muscle cells also appeared to
      move from the cut muscle edges of both the muscularis mucosa and the lamina
      muscularis and were seen as a layer of several cells under newly formed mucosa.
      Double staining of the basal membrane of the ingrowing vessels and the pericytes
      showed that the basal membrane was thinner over some of the pericytes, but there
      was no accumulation of immature-looking cells in the submucosa of the bridging
      area. In this porcine model, where esophageal regrowth was studied by using a
      bridging graft composed of a silicone stented Biodesign mesh, we can conclude
      that leakage increased the inflammatory response in early healing. Ingrowth of
      new vessels was seen in the bridging area and movement of smooth muscle cells was
      found under newly formed mucosa. 

PMID- 24571650
TI  - Correlation of EGFR mutation status with predominant histologic subtype of
      adenocarcinoma according to the new lung adenocarcinoma classification of the
      International Association for the Study of Lung Cancer/American Thoracic
      Society/European Respiratory Society.
AB  - CONTEXT: Epidermal growth factor receptor (EGFR) mutations have been identified
      as predictors of response to EGFR tyrosine kinase inhibitors in non-small cell
      lung cancer. OBJECTIVE: To investigate the relationship of EGFR mutation status
      to the histologic subtype of adenocarcinoma according to the new International
      Association for the Study of Lung Cancer (IASLC)/American Thoracic Society
      (ATS)/European Respiratory Society (ERS) classification. DESIGN: We screened EGFR
      mutation in 200 consecutive lung adenocarcinoma resection specimens diagnosed
      between 2008 and 2011. RESULTS: Among 200 lung adenocarcinomas, EGFR mutations
      were identified in 41 tumors (20.5%). The mean age in the EGFR-mutant group was
      64.8 years and this group consisted of 78% females and 22% males. Most patients
      with EGFR-positive lung cancers were never-smokers (51%) as compared to 8% with
      EGFR-negative cancers (P < .001). The most common mutations identified in our
      population were deletions in exon 19 (22 patients) and L858R in exon 21 (12
      patients). Five patients had double mutations. The predominant pattern of
      adenocarcinoma was lepidic (44%) in EGFR-mutant lung cancers as compared to 69%
      with acinar pattern in EGFR wild-type lung cancers (P < .001). Of 22 minimally
      invasive adenocarcinomas, 8 (36%) had EGFR mutations, accounting for 20% of
      adenocarcinomas with EGFR mutations (P < .05). CONCLUSIONS: Based on the new
      IASLC/ATS/ERS classification, the predominant subtype of adenocarcinoma was
      lepidic (44%) in EGFR-mutant lung cancers (P < .001). However, histologic subtype
      should not be used to exclude patients from tyrosine kinase inhibitor therapy,
      since EGFR mutations are found in lung adenocarcinomas of other subtypes.

PMID- 24571648
TI  - Aggregates of small nuclear ribonucleic acids (snRNAs) in Alzheimer's disease.
AB  - We recently discovered that protein components of the ribonucleic acid (RNA)
      spliceosome form cytoplasmic aggregates in Alzheimer's disease (AD) brain,
      resulting in widespread changes in RNA splicing. However, the involvement of
      small nuclear RNAs (snRNAs), also key components of the spliceosome complex, in
      the pathology of AD remains unknown. Using immunohistochemical staining of post
      mortem human brain and spinal cord, we identified cytoplasmic tangle-shaped
      aggregates of snRNA in both sporadic and familial AD cases but not in aged
      controls or other neurodegenerative disorders. Immunofluorescence using
      antibodies reactive with the 2,2,7-trimethylguanosine cap of snRNAs and
      transmission electron microscopy demonstrated snRNA localization with tau and
      paired helical filaments, the main component of neurofibrillary tangles.
      Quantitative real-time polymerase chain reaction (PCR) showed U1 snRNA
      accumulation in the insoluble fraction of AD brains whereas other U snRNAs were
      not enriched. In combination with our previous results, these findings
      demonstrate that aggregates of U1 snRNA and U1 small nuclear ribonucleoproteins
      represent a new pathological hallmark of AD. 

PMID- 24571652
TI  - Maternal mortality revisited: the application of the new ICD-MM classification
      system in reference to maternal deaths in Sri Lanka.
AB  - BACKGROUND: The recently published WHO guidelines on applications of ICD-10 to
      deaths during pregnancy, childbirth, and the puerperium (ICD-MM) aimed at
      enabling a comprehensive framework for international comparison of maternal
      deaths, which includes maternal suicides as a direct cause of maternal deaths. At
      present, most developing countries do not include suicide as a maternal death.
      METHODS: We extracted and analysed data from the maternal death surveillance
      system in North Central Province of Sri Lanka for the period of 2005 to 2011, in
      order to identify the implications of this new classification on maternal
      mortality estimates. All reported deaths of pregnant women and women within 12
      months of termination of pregnancy were included in this study. Causes of deaths
      were extracted and coded using ICD-10 reclassified according to new ICD-MM for
      maternal deaths. RESULTS: Of the 118 deaths analysed, the maternal death
      investigation system had classified 53 (44.9%) deaths as maternal deaths. These
      53 maternal deaths included one deaths due to suicied, out of 21 (17.8%) suicide
      deaths among 118 reported deaths. Application of the new ICD-MM showed 83
      maternal deaths which resulted in a 56.6% increase of number of maternal deaths
      in the province. Detailed analysis of all individual causes by ICD 10 codes
      showed that intentional self-poisoning by an exposure to pesticide (ICD code X63)
      as the leading cause of maternal deaths in NCP (n = 11, 13.3% of all maternal
      deaths) during this period. The estimated MMR in the study area based on the new
      classification in years 2009, 2010 and 2011 was 115, 103 and 88 per 100,000 live
      births respectively. CONCLUSIONS: The new classification system may have an
      immediate effect in raising maternal mortality thresholds, making the MDG Goal 5A
      more elusive for many countries. However, this new approach may ultimately lead
      to a more accurate understanding of maternal mortality, as well as the real
      number of maternal deaths attributed to suicide. This more accurate accounting
      has implications for policymakers andpractitioners globally as they strive to
      meet women's needs during pregnancy, including attention to detection and
      treatment for maternal depression, given its close correlation with maternal
      suicide.

PMID- 24571651
TI  - Patient engagement as a risk factor in personalized health care: a systematic
      review of the literature on chronic disease.
AB  - BACKGROUND: The role of patient engagement as an important risk factor for
      healthcare outcomes has not been well established. The objective of this article
      was to systematically review the relationship between patient engagement and
      health outcomes in chronic disease to determine whether patient engagement should
      be quantified as an important risk factor in health risk appraisals to enhance
      the practice of personalized medicine. METHODS: A systematic review of
      prospective clinical trials conducted between January 1993 and December 2012 was
      performed. Articles were identified through a medical librarian-conducted multi
      term search of Medline, Embase, and Cochrane databases. Additional studies were
      obtained from the references of meta-analyses and systematic reviews on
      hypertension, diabetes, and chronic care. Search terms included variations of the
      following: self-care, self-management, self-monitoring, (shared) decision-making,
      patient education, patient motivation, patient engagement, chronic disease,
      chronically ill, and randomized controlled trial. Studies were included only if
      they: (1) compared patient engagement interventions to an appropriate control
      among adults with chronic disease aged 18 years and older; (2) had minimum 3
      months between pre- and post-intervention measurements; and (3) defined patient
      engagement as: (a) understanding the importance of taking an active role in one's
      health and health care; (b) having the knowledge, skills, and confidence to
      manage health; and (c) using knowledge, skills and confidence to perform health
      promoting behaviors. Three authors and two research assistants independently
      extracted data using predefined fields including quality metrics. RESULTS: We
      reviewed 543 abstracts to identify 10 trials that met full inclusion criteria,
      four of which had 'high' methodological quality (Jadad score >= 3). Diverse
      measurement of patient engagement prevented robust statistical analyses, so data
      were qualitatively described. Nine studies documented improvements in patient
      engagement. Five studies reported reduction in clinical markers of disease (for
      example HbA1C). All studies reported improvements in self-reported health status.
      CONCLUSIONS: This review suggests patient engagement should be quantified as part
      of a comprehensive health risk appraisal given its apparent value in helping
      individuals to effectively self-manage chronic disease. Patient engagement
      measures should include assessment of the knowledge, confidence and skills to
      prevent and manage chronic disease, plus the behaviors to do so.

PMID- 24571653
TI  - Assessment of vascularized free fibula transplantation revealing a congenital
      aplastic posterior tibial artery: a case report.
AB  - INTRODUCTION: Anatomical abnormalities in the lower limb vessels are uncommon.
      However, the preoperative evaluation of the anatomical variations is very
      important for planning the operation procedure to prevent jeopardizing the donor
      leg. CASE PRESENTATION: In this case report, a 23-year-old Asian woman who was
      scheduled to have vascularized free fibula transplantation for reconstruction of
      her wrist after excision of bone tumor in her distal radius, was found to have
      congenital aplastic posterior tibial arteries in both legs. These findings were
      found on magnetic resonance angiography (our preferred methodology due to its
      simplicity). We planned testing the sufficiency of her pedal pulses after
      temporarily clamping her peroneal artery but prior to harvesting, to ensure
      minimal risk to the longevity of her donor leg. During the operation, after
      dissection of a 10cm segment of her fibula with the peroneal artery, the peroneal
      artery proximal to the graft was temporarily clamped and the tourniquet was
      released. As adequate sustainable pedal pulses were confirmed, the graft was
      harvested and transplanted to her wrist. There was no morbidity in her right leg
      postoperatively and the union of the grafted fibula was substantiated 10 months
      postoperatively. CONCLUSIONS: We concluded two findings: firstly, for accurate
      preoperative planning of a vascularized free fibula procedure, examination of the
      bilateral lower leg vasculature either by angiography or other imaging should be
      performed. Secondly, abnormalities are not in themselves reason to abandon the
      vascularized free fibula procedure. We contend that pedal pulses should be
      evaluated preoperatively and provided that adequate foot circulation can be
      confirmed (by temporarily clamping the vessels and releasing the tourniquet
      during the operation prior to harvesting the free vascularized fibula) the
      procedure should be successful without jeopardizing the donor leg.

PMID- 24571654
TI  - Age-related changes in 24-hour urine composition must be considered in the
      medical management of nephrolithiasis.
AB  - BACKGROUND AND PURPOSE: Over the past 50 years, there has been an upward shift in
      the age of peak incidence of stone disease, yet less is known regarding how the
      urinary biochemical profile changes with aging. Therefore, we sought to examine
      the relationship between age and 24-hour urine composition. METHODS: We
      retrospectively reviewed a database of our tertiary care stone clinic patients
      seen from March 2002 to February 2012. Analysis of pretreatment 24-hour urine
      collections across age groups was performed using univariate analysis of variance
      and multivariate linear regression models adjusting for clinical and demographic
      factors and 24-hour urine parameters. RESULTS: A total of 1115 patients were
      broken down into age groups consisting of <45 years (221; 19.7%), 45-54.9 years
      (270; 23.8%), 55-64.9 years (270; 24.6%), and >=65 years (356; 31.9%). Univariate
      analysis found significant ascending trends with aging for mean body mass index,
      while mean urine pH, 24-hour calcium, uric acid (UA), ammonium, creatinine, and
      supersaturation (SS) of calcium oxalate (CaOx) and calcium phosphate (CaP)
      decreased with age (all P for trend <0.05). Adjusted multivariate analysis
      demonstrated that increased age was significantly associated with increased 24
      hour citrate and SS UA, whereas increased age was significantly associated with
      decreased pH, 24-hour UA, creatinine, SS CaOx, and SS CaP (all P for trend
      <0.05). CONCLUSIONS: There are numerous age-related changes in the metabolic
      profile as seen on 24-hour urine collection. This highlights the importance of
      evaluating stone-forming patients of all ages with 24-hour urine collections
      because both the type and degree of metabolic abnormality may change with age.

PMID- 24571655
TI  - A solid chelating ligand: periodic mesoporous organosilica containing 2,2'
      bipyridine within the pore walls.
AB  - Synthesis of a solid chelating ligand for the formation of efficient
      heterogeneous catalysts is highly desired in the fields of organic transformation
      and solar energy conversion. Here, we report the surfactant-directed self
      assembly of a novel periodic mesoporous organosilica (PMO) containing 2,2'
      bipyridine (bpy) ligands within the framework (BPy-PMO) from a newly synthesized
      organosilane precursor [(i-PrO)3Si-C10H6N2-Si(Oi-Pr)3] without addition of any
      other silane precursors. BPy-PMO had a unique pore-wall structure in which
      bipyridine groups were densely and regularly packed and exposed on the surface.
      The high coordination ability to metals was also preserved. Various bipyridine
      based metal complexes were prepared using BPy-PMO as a solid chelating ligand
      such as Ru(bpy)2(BPy-PMO), Ir(ppy)2(BPy-PMO) (ppy = 2-phenylpyridine),
      Ir(cod)(OMe)(BPy-PMO) (cod = 1,5-cyclooctadiene), Re(CO)3Cl(BPy-PMO), and
      Pd(OAc)2(BPy-PMO). BPy-PMO showed excellent ligand properties for heterogeneous
      Ir-catalyzed direct C-H borylation of arenes, resulting in superior activity,
      durability, and recyclability to the homogeneous analogous Ir catalyst. An
      efficient photocatalytic hydrogen evolution system was also constructed by
      integration of a Ru-complex as a photosensitizer and platinum as a catalyst on
      the pore surface of BPy-PMO without any electron relay molecules. These results
      demonstrate the great potential of BPy-PMO as a solid chelating ligand and a
      useful integration platform for construction of efficient molecular-based
      heterogeneous catalysis systems. 

PMID- 24571657
TI  - Core size conversion: route for exclusive synthesis of Au38 or Au40
      nanomolecules.
AB  - Gold nanomolecules with a precise number of gold atoms and ligands have promise
      for catalytic, optical, and biomedical applications. For practical applications,
      it is essential to develop synthetic protocols to prepare monodisperse gold
      nanomolecules. A typical synthesis yields a number of nanomolecules with discrete
      numbers of core atoms. Thermochemical treatment in the presence of excess thiol,
      etching, is known to narrow down the number of discrete nanomolecules, by
      selective degradation of sizes with lower stability. Au38(SR)24 and Au40(SR)24
      are abundantly formed in these etching reactions due to their extraordinary
      stability to chemical etching. These nanomolecules are of high interest due in
      part to its stability, X-ray crystallographic structure availability (Au38), and
      intrinsic chirality arising from the arrangement of the Au-SR interface. However,
      the synthetic routes typically yield a mixture of Au38 and Au40, demanding
      extensive separation protocols. Here, we present a synthetic route to prepare
      either Au38 or Au40 exclusively in the product of etching. This was made possible
      by conducting a comprehensive mechanistic study starting from single-sized
      reactant. Au67 on etching yields Au40 exclusively. Au(103-105)(SR)(45-46) on
      etching also yields Au40 exclusively. Clusters of various sizes smaller than Au67
      on etching yield Au38 exclusively. This is the first direct evidence for the
      exclusive formation of Au38 and Au40 nanomolecules by core size conversion. Mass
      spectrometry was used to study the core size conversion reactions to understand
      the mechanism. Au38 and Au40 nanomolecules form via different intermediates, as
      observed in the mass spectrometry data.

PMID- 24571658
TI  - Bio-based ionic liquid crystalline quaternary ammonium salts: properties and
      applications.
AB  - In the present work, we describe the preparation, properties, and applications of
      novel ionic liquid crystalline quaternary ammonium salts (QSs) of 3
      pentadecylphenol, a bio-based low-cost material derived from cashew nut shell
      liquid. Amphotropic liquid crystalline phase formation in QSs was characterized
      using a combination of techniques, such as DSC, PLM, XRD, SEM, and rheology,
      which revealed the formation of one, two, and three dimensionally ordered
      mesophases in different length scales. On the basis of these results, a plausible
      mechanism for the formation of specific modes of packing in various mesophases
      was proposed. Observation of anisotropic ionic conductivity and electrochemical
      stability suggests their application as a solid electrolyte. 

PMID- 24571656
TI  - Bayesian hidden Markov models to identify RNA-protein interaction sites in PAR
      CLIP.
AB  - The photoactivatable ribonucleoside enhanced cross-linking immunoprecipitation
      (PAR-CLIP) has been increasingly used for the global mapping of RNA-protein
      interaction sites. There are two key features of the PAR-CLIP experiments: The
      sequence read tags are likely to form an enriched peak around each RNA-protein
      interaction site; and the cross-linking procedure is likely to introduce a
      specific mutation in each sequence read tag at the interaction site. Several ad
      hoc methods have been developed to identify the RNA-protein interaction sites
      using either sequence read counts or mutation counts alone; however, rigorous
      statistical methods for analyzing PAR-CLIP are still lacking. In this article, we
      propose an integrative model to establish a joint distribution of observed read
      and mutation counts. To pinpoint the interaction sites at single base-pair
      resolution, we developed a novel modeling approach that adopts non-homogeneous
      hidden Markov models to incorporate the nucleotide sequence at each genomic
      location. Both simulation studies and data application showed that our method
      outperforms the ad hoc methods, and provides reliable inferences for the RNA
      protein binding sites from PAR-CLIP data. 

PMID- 24571659
TI  - Deterministic optical-near-field-assisted positioning of nitrogen-vacancy
      centers.
AB  - Nanopositioning of single quantum emitters to control their coupling to
      integrated photonic structures is a crucial step in the fabrication of solid
      state quantum optics devices. We use the optical near-field enhancement produced
      by nanofabricated gold antennas subject to near-infrared illumination to
      deterministically trap and position single nanodiamonds (NDs) hosting nitrogen
      vacancy (NV) centers. The positioning of the NDs at the antenna regions of
      maximum field intensity is first characterized using both fluorescence and
      electron microscopy imaging. We further study the interaction between the
      nanoantenna and the delivered NV center by analyzing its change in fluorescence
      lifetime, which is driven by the increase in the local density of optical states
      at the trapping positions. Additionally, the plasmonic enhancement of the near
      field intensity allows us to optically control the NV excited lifetime using
      relatively low NIR illumination intensities, some 20 times lower than in the
      absence of the antennas. 

PMID- 24571660
TI  - Breaking the glass ceiling: an interview with Dr. Shirley Graves, a pioneering
      woman in medicine.
AB  - Shirley Graves M.D., D.Sc. (honorary) (1936), Professor Emeritus of
      Anesthesiology and Pediatrics at the University of Florida, was one of the most
      influential women in medicine in the 1960 and 1970s, a time when the medical
      profession was overwhelmingly male-dominated. In today's society, it is hard to
      believe that only 50 years ago, women were scarce in the field of medicine. Yet
      Dr. Graves was a pioneer in the fields of pediatric anesthesia and pediatric
      critical care medicine. She identifies her development of the pediatric intensive
      care unit and her leadership in the Division of Pediatric Anesthesia at the
      University of Florida as her defining contributions. Through her journal
      articles, book chapters, national and international lectures, and leadership in
      the American Society of Anesthesiology and the Florida Society of Anesthesiology,
      she inspired a generation of men and women physicians to conquer the unthinkable
      and break through the glass ceiling.

PMID- 24571661
TI  - Being a mindful clinical teacher: can mindfulness enhance education in a clinical
      setting?
AB  - Mindfulness may be viewed as a vehicle to promote the healer's role in medicine.
      This role addresses the way in which a medical practitioner interacts with
      patients. The aim of this article is to highlight how mindful qualities may also
      enhance teaching in clinical settings. Challenges to being a mindful clinical
      teacher are presented along with creative ways to accommodate them. Residents
      play an important role in training medical students. Examples of how mindfulness
      influenced a psychiatric resident's teaching experiences are presented to
      illustrate the concepts discussed herein. The dimension of "being" in medicine,
      based on the humanist philosophy of Dr Karl Jaspers, is provided as a framework
      for this article.

PMID- 24571663
TI  - Introduction to a Virtual Special Issue: modeling the hidden half - the root of
      our problem.

PMID- 24571664
TI  - Flow-limiting valve for ABA signalling in stomatal guard cells.

PMID- 24571665
TI  - Informing the improvement and biodesign of crassulacean acid metabolism via
      system dynamics modelling.

PMID- 24571666
TI  - Evidence for regulation of columnar habit in apple by a putative 2OG-Fe(II)
      oxygenase.
AB  - Understanding the genetic mechanisms controlling columnar-type growth in the
      apple mutant 'Wijcik' will provide insights on how tree architecture and growth
      are regulated in fruit trees. In apple, columnar-type growth is controlled by a
      single major gene at the Columnar (Co) locus. By comparing the genomic sequence
      of the Co region of 'Wijcik' with its wild-type 'McIntosh', a novel non-coding
      DNA element of 1956 bp specific to Pyreae was found to be inserted in an
      intergenic region of 'Wijcik'. Expression analysis of selected genes located in
      the vicinity of the insertion revealed the upregulation of the MdCo31 gene
      encoding a putative 2OG-Fe(II) oxygenase in axillary buds of 'Wijcik'.
      Constitutive expression of MdCo31 in Arabidopsis thaliana resulted in compact
      plants with shortened floral internodes, a phenotype reminiscent of the one
      observed in columnar apple trees. We conclude that MdCo31 is a strong candidate
      gene for the control of columnar growth in 'Wijcik'. 

PMID- 24571662
TI  - Accelerating clinical development of HIV vaccine strategies: methodological
      challenges and considerations in constructing an optimised multi-arm phase I/II
      trial design.
AB  - BACKGROUND: Many candidate vaccine strategies against human immunodeficiency
      virus (HIV) infection are under study, but their clinical development is lengthy
      and iterative. To accelerate HIV vaccine development optimised trial designs are
      needed. We propose a randomised multi-arm phase I/II design for early stage
      development of several vaccine strategies, aiming at rapidly discarding those
      that are unsafe or non-immunogenic. METHODS: We explored early stage designs to
      evaluate both the safety and the immunogenicity of four heterologous prime-boost
      HIV vaccine strategies in parallel. One of the vaccines used as a prime and boost
      in the different strategies (vaccine 1) has yet to be tested in humans, thus
      requiring a phase I safety evaluation. However, its toxicity risk is considered
      minimal based on data from similar vaccines. We newly adapted a randomised phase
      II trial by integrating an early safety decision rule, emulating that of a phase
      I study. We evaluated the operating characteristics of the proposed design in
      simulation studies with either a fixed-sample frequentist or a continuous
      Bayesian safety decision rule and projected timelines for the trial. RESULTS: We
      propose a randomised four-arm phase I/II design with two independent binary
      endpoints for safety and immunogenicity. Immunogenicity evaluation at trial end
      is based on a single-stage Fleming design per arm, comparing the observed
      proportion of responders in an immunogenicity screening assay to an unacceptably
      low proportion, without direct comparisons between arms. Randomisation limits
      heterogeneity in volunteer characteristics between arms. To avoid exposure of
      additional participants to an unsafe vaccine during the vaccine boost phase, an
      early safety decision rule is imposed on the arm starting with vaccine 1
      injections. In simulations of the design with either decision rule, the risks of
      erroneous conclusions were controlled <15%. Flexibility in trial conduct is
      greater with the continuous Bayesian rule. A 12-month gain in timelines is
      expected by this optimised design. Other existing designs such as bivariate or
      seamless phase I/II designs did not offer a clear-cut alternative. CONCLUSIONS:
      By combining phase I and phase II evaluations in a multi-arm trial, the proposed
      optimised design allows for accelerating early stage clinical development of HIV
      vaccine strategies.

PMID- 24571667
TI  - NF-kappaB-dependent microRNA-425 upregulation promotes gastric cancer cell growth
      by targeting PTEN upon IL-1beta induction.
AB  - Overexpression of the proinflammatory cytokine IL-1beta is associated with
      diverse diseases, including cancer. Alteration of microRNAs has been observed in
      cancer cells exposed to proinflammatory cytokines, yet their function in
      inflammation stress remains elusive. Here, we show that IL-1beta induces the
      upregulation of miR-425, which negatively regulates phosphatase and tensin
      homolog expression by targeting its 3' UTR. An increase in miR-425 depends on IL
      1beta-induced NF-kappaB activation, which enhances miR-425 gene transcription
      upon IL-1beta induction. Consequently, repression of phosphatase and tensin
      homolog by miR-425 promotes gastric cancer cell proliferation, which is required
      to protect cells from cisplatin-induced apoptosis. Taken together, our data
      support a critical role for NF-kappaB-dependent upregulation of miR-425, which
      represents a new pathway for the repression of phosphatase and tensin homolog
      activation and the promotion of cell survival upon IL-1beta induction.

PMID- 24571669
TI  - Secretome profiling reveals the signaling molecules of apoptotic HCT116 cells
      induced by the dietary polyacetylene gymnasterkoreayne B.
AB  - Dietary polyacetylenes from various foods have been receiving attention as
      promising cancer chemopreventive agents. However, until now, the detailed
      molecular mechanism and the regulatory proteins underlying these effects have not
      been elucidated. We investigated the effects of gymnasterkoreayne B (GKB), a
      model dietary polyacetylene from wild vegetables, on the programmed cell death of
      HCT116 human colorectal cancer cells. GKB inhibited HCT116 cell proliferation by
      inducing apoptotic cell death. GKB treatment resulted in ROS accumulation,
      leading to the activation of both intrinsic and extrinsic apoptotic pathway. We
      also found that FN1, TGFB1, APP, SERPINE1, HSPD1, SOD1, TXN, and ACTN4 may act as
      secretory signaling molecules during GKB-induced apoptotic cell death using LC
      MS/MS identification followed by spectrum counting, statistical calculation, and
      gene ontology analysis. The secretory proteins suggested in this study may be
      promising candidates involved in apoptotic cell death of cancer cells induced by
      GKB that warrant further functional study.

PMID- 24571670
TI  - How many bubbles in your glass of bubbly?
AB  - The issue about how many carbon dioxide bubbles are likely to nucleate in a glass
      of champagne (or bubbly) is of concern for sommeliers, wine journalists,
      experienced tasters, and any open minded physical chemist wondering about complex
      phenomena at play in a glass of bubbly. The whole number of bubbles likely to
      form in a single glass is the result of the fine interplay between dissolved CO2,
      tiny gas pockets trapped within particles acting as bubble nucleation sites, and
      ascending bubble dynamics. Based on theoretical models combining ascending bubble
      dynamics and mass transfer equations, the falsely naive question of how many
      bubbles are likely to form per glass is discussed in the present work. A
      theoretical relationship is derived, which provides the whole number of bubbles
      likely to form per glass, depending on various parameters of both the wine and
      the glass itself. 

PMID- 24571668
TI  - Pattern and severity of early childhood caries in Southern Italy: a preschool
      based cross-sectional study.
AB  - BACKGROUND: This survey was intended to investigate prevalence and severity of
      early childhood caries (ECC) in a sample of children in Southern Italy and to
      identify factors that may be related to this condition. METHODS: The study was
      designed as a cross-sectional survey. The study population (children aged 36-71
      months) attending thirteen kindergartens was randomly selected through a two
      stage cluster sampling procedure. Parents/guardians of all eligible children were
      invited to participate filling out a structured self-administered questionnaire,
      and after having returned the informed consent form an oral examination of the
      child was performed at school. The questionnaire included information on: socio
      demographics about parents/guardians and child, pregnancy and newborn
      characteristics, oral hygiene habits of child, eating habits particularly on
      consumption of sweets, access to dental services, and infant feeding practices.
      The WHO caries diagnostic criteria for deciduous decayed, missing and filled
      teeth (dmft) and surfaces (dmfs) were used to record ECC and severe-ECC (S-ECC).
      Univariate and multiple logistic regression analyses were conducted to evaluate
      statistical associations of social demographics, infant feeding practices, oral
      hygiene habits, and access to dental services to ECC, S-ECC, dmft and dmfs.
      RESULTS: 515 children participated in the study. 19% had experienced ECC, and
      2.7% severe-ECC (S-ECC), with a mean dmft and dmfs scores of 0.51 and 0.99,
      respectively. Mean dmft was 2.68 in ECC subjects, and 6.86 in S-ECC subjects.
      Statistical analysis showed that prevalence of ECC significantly increased with
      age (OR = 1.95; 95% CI = 1.3-2.91) and duration of breastfeeding (OR = 1.26; 95%
      CI = 1.01-1.57), whereas it was significantly lower in children of more educated
      mothers (OR = 0.64; 95% CI = 0.42-0.96), and higher in those who had been visited
      by a dentist in the previous year (OR = 3.29; 95% CI = 1.72-6.33). CONCLUSIONS:
      Results of our study demonstrate that even in Western countries ECC and S-ECC
      represent a significant burden in preschool children, particularly in those
      disadvantaged, and that most of the known modifiable associated factors regarding
      feeding practices and oral hygiene are still very spread in the population.

PMID- 24571671
TI  - Treatment of the acute sickle cell vaso-occlusive crisis in the Emergency
      Department: a Brazilian method of switching from intravenous to oral morphine.
AB  - OBJECTIVES: Describe the treatment of patients with vaso-occlusive crises (VOC)
      in a Brazilian emergency department (ED) and the successful switch from
      intravenous to oral morphine. PATIENTS AND METHODS: We analyzed records of 315
      patients with sickle cell disease using two different protocols for pain: one in
      March 2010 prescribing intravenous morphine every 4 h throughout their stay, and
      another in March 2011 and 2012 prescribing one initial dose of intravenous
      morphine followed by equianalgesic doses of oral morphine every 4 h. Patients
      were triaged into three groups: mild, moderate, and severe VOC. The mild group
      was treated within 1 h after triage, the moderate within 30 min and the severe
      was treated immediately. Patients whose pain was not relieved within 6 h after
      the first dose of morphine were transferred into a different holding area of the
      ED where they continued to receive the same treatment for 48 h after which they
      were hospitalized if still in pain. RESULTS: The number of patients who stayed
      <24 h in the ED increased significantly from 63 in 2010 to 87 in 2012, and the
      number of admissions decreased from 26 in 2010 to 10 in 2012. The incidence of
      acute chest syndrome decreased from 8.5% in 2010 to 1.9% in 2012. CONCLUSION:
      Patients treated with oral morphine stayed a shorter time in the ED, had more
      pain relief, were admitted less frequently, and had less acute chest syndrome.
      These differences may be due to environmental, cultural, psychological, and
      pharmacogenetic factors.

PMID- 24571672
TI  - Bilateral renal ischemia after kyphoplasty and clodronate treatment: a case
      report.
AB  - INTRODUCTION: The most common adverse effects associated with bisphosphonates are
      renal toxicity, acute-phase reactions, gastrointestinal toxicity, osteonecrosis
      of the jaw, transitory fever and uveitis. We report a unique adverse case of
      vasculitis induced by clodronate. CASE PRESENTATION: A 61-year-old Caucasian
      woman developed bilateral renal ischemia after kyphoplasty and clodronate
      treatment for lumbar vertebral fracture. Tests revealed a vasculitis due to
      clodronate treatment. The antithrombotic and immunosuppressive drugs allowed us
      to reduce the extent of the renal ischemia. In the following months the increased
      auto-antibodies returned to the healthy physiological range, but the chronic
      renal failure persisted. CONCLUSIONS: Drug-induced vasculitis is an inflammation
      of blood vessels caused by the use of various pharmaceutical agents. The spectrum
      of drug-induced vasculitis can range from cutaneous rashes to fatal multi-organ
      involvement. To the best of our knowledge this is the first documented case of
      drug-induced vasculitis caused by clodronate in the literature. Previously, it
      was verified that clodronate injection could increase the pro-apoptotic action on
      immune cells. Further studies are necessary to clarify the role of
      bisphosphonates on drug-inducing vasculitis.

PMID- 24571674
TI  - A new bisanthraquinone and cytotoxic xanthones from Cratoxylum cochinchinense.
AB  - A new bisanthraquinone has been isolated from the stems of Cratoxylum
      cochinchinense together with vismiaquinone C and 16 known xanthones. Their
      structures were characterised by using spectroscopic methods. Two of the isolated
      compounds are modified xanthones (6 and 15) and exhibited strong cytotoxicity
      against human epidermoid carcinoma (A341: IC50 2.01, 1.78 MUg/mL) and human
      breast cancer cell lines (SKBR3: IC50 1.54, 0.69 MUg/mL). 

PMID- 24571675
TI  - Multiplexed homogeneous assays of proteolytic activity using a smartphone and
      quantum dots.
AB  - Semiconductor quantum dot (QD) bioconjugates, with their unique and highly
      advantageous physicochemical and optical properties, have been extensively
      utilized as probes for bioanalysis and continue to generate widespread interest
      for these applications. An important consideration for expanding the utility of
      QDs and making their use routine is to make assays with QDs more accessible for
      laboratories that do not specialize in nanomaterials. Here, we show that digital
      color imaging of QD photoluminescence (PL) with a smartphone camera is a viable,
      easily accessible readout platform for quantitative, multiplexed, and real-time
      bioanalyses. Red-, green-, and blue-emitting CdSeS/ZnS QDs were conjugated with
      peptides that were labeled with a deep-red fluorescent dye, Alexa Fluor 647, and
      the dark quenchers, QSY9 and QSY35, respectively, to generate Forster resonance
      energy transfer (FRET) pairs sensitive to proteolytic activity. Changes in QD PL
      caused by the activity of picomolar to nanomolar concentrations of protease were
      detected as changes in the red-green-blue (RGB) channel intensities in digital
      color images. Importantly, measurements of replicate samples made with smartphone
      imaging and a sophisticated fluorescence plate reader yielded the same
      quantitative results, including initial proteolytic rates and specificity
      constants. Homogeneous two-plex and three-plex assays for the activity of
      trypsin, chymotrypsin, and enterokinase were demonstrated with RGB imaging. Given
      the ubiquity of smartphones, this work largely removes any instrumental
      impediments to the adoption of QDs as routine tools for bioanalysis in research
      laboratories and is a critical step toward the use of QDs for point-of-care
      diagnostics. This work also adds to the growing utility of smartphones in
      analytical methods by enabling multiplexed fluorimetric assays within a single
      sample volume and across multiple samples in parallel. 

PMID- 24571673
TI  - Integrated genomic and prospective clinical studies show the importance of
      modular pleiotropy for disease susceptibility, diagnosis and treatment.
AB  - BACKGROUND: Translational research typically aims to identify and functionally
      validate individual, disease-specific genes. However, reaching this aim is
      complicated by the involvement of thousands of genes in common diseases, and that
      many of those genes are pleiotropic, that is, shared by several diseases.
      METHODS: We integrated genomic meta-analyses with prospective clinical studies to
      systematically investigate the pathogenic, diagnostic and therapeutic roles of
      pleiotropic genes. In a novel approach, we first used pathway analysis of all
      published genome-wide association studies (GWAS) to find a cell type common to
      many diseases. RESULTS: The analysis showed over-representation of the T helper
      cell differentiation pathway, which is expressed in T cells. This led us to focus
      on expression profiling of CD4(+) T cells from highly diverse inflammatory and
      malignant diseases. We found that pleiotropic genes were highly interconnected
      and formed a pleiotropic module, which was enriched for inflammatory, metabolic
      and proliferative pathways. The general relevance of this module was supported by
      highly significant enrichment of genetic variants identified by all GWAS and
      cancer studies, as well as known diagnostic and therapeutic targets. Prospective
      clinical studies of multiple sclerosis and allergy showed the importance of both
      pleiotropic and disease specific modules for clinical stratification.
      CONCLUSIONS: In summary, this translational genomics study identified a
      pleiotropic module, which has key pathogenic, diagnostic and therapeutic roles.

PMID- 24571677
TI  - Test the reliability of doubly robust estimation with missing response data.
AB  - In statistical inference, one has to make sure that the underlying regression
      model is correctly specified otherwise the resulting estimation may be biased.
      Model checking is an important method to detect any departure of the regression
      model from the true one. Missing data are a ubiquitous problem in social and
      medical studies. If the underlying regression model is correctly specified,
      recent researches show great popularity of the doubly robust (DR) estimates
      method for handling missing data because of its robustness to the
      misspecification of either the missing data model or the conditional mean model,
      that is, the model for the conditional expectation of true regression model
      conditioning on the observed quantities. However, little work has been devoted to
      the goodness of fit test for DR estimates method. In this article, we propose a
      testing method to assess the reliability of the estimator derived from the DR
      estimating equation with possibly missing response and always observed auxiliary
      variables. Numerical studies demonstrate that the proposed test can control type
      I errors well. Furthermore the proposed method can detect departures from model
      assumptions in the marginal mean model of interest powerfully. A real dementia
      data set is used to illustrate the method for the diagnosis of model
      misspecification in the problem of missing response with an always observed
      auxiliary variable for cross-sectional data.

PMID- 24571676
TI  - RAS mutations in early age leukaemia modulated by NQO1 rs1800566 (C609T) are
      associated with second-hand smoking exposures.
AB  - BACKGROUND: Deregulation of the MAPK genes signalling caused by somatic mutations
      have been implied in leukaemia pathogenesis, including RAS mutation (RASmut) in
      acute myeloid leukaemia (AML), which has been associated with intra-uterine
      chemical exposures. A case-case study was conducted in order to explore maternal
      and child exposures to tobacco smoking associations with early age leukaemia
      (EAL). METHODS: Covariables of reference were MLL rearrangements (MLL-r), RASmut
      and NQO1 rs1800566 (C609T). Samples from 150 acute lymphoblastic leukaemia (ALL)
      and 85 AML were included. Maternal exposures were assessed using a structured
      questionnaire with demographic, personal habits and residence history
      information. Restriction fragment length polymorphism and denaturing high
      performance liquid chromatography were used to screen FLT3, KRAS, and NRAS
      mutations; direct sequencing was performed to validate the results. NQO1
      polymorphism was detected by real-time allelic discrimination technique. RESULTS:
      Overall, RASmut were detected in 28.7% of EAL cases; BRAFmut was found only in
      one AML patient. Higher rate of KRASmut was found in ALL (30.3%) compared to AML
      (20.8%) with MLL-r; RASmut showed an association with second-hand tobacco smoking
      exposures (OR, 3.06, 95% CI, 1.03-9.07). A considerable increased risk for EAL
      with the combination of RASmut and NQO1 609CT (OR, 4.24, 95% CI, 1.24-14.50) was
      observed. CONCLUSIONS: Our data demonstrated the increased risk association
      between maternal smoking and EAL with MLL-r. Additionally, suggests that children
      second-hand tobacco exposures are associated with increased risk of EAL with
      RASmut modulated by NQO1 rs1800566 (C609T).

PMID- 24571678
TI  - The hygroscopic biosurfactant syringafactin produced by Pseudomonas syringae
      enhances fitness on leaf surfaces during fluctuating humidity.
AB  - Biosurfactant production by bacteria on leaf surfaces is poorly documented, and
      its role in this habitat has not been explored. Therefore, we investigated the
      production and fitness benefits of syringafactin by Pseudomonas syringae pv.
      syringae B728a on leaves. Syringafactin largely adsorbed to the waxy leaf cuticle
      both when topically applied and when produced by cells on plants. Syringafactin
      increased the rate of diffusion of water across isolated cuticles and attracted
      water to hydrophobic surfaces exposed to high relative humidity due to its
      hygroscopic properties. While a wild-type and syringafactin mutant exhibited
      similar fitness on bean leaves incubated in static conditions, the fitness of the
      wild-type strain was higher under fluctuating humidity conditions typical of
      field conditions. When co-inoculated onto either the host plant bean or the non
      host plant romaine lettuce, the proportion of viable wild-type cells recovered
      from plants relative to that of a mutant unable to produce syringafactin
      increased 10% over 10 days. The number of disease lesions incited by the wild
      type strain on bean was also significantly higher than that of the syringafactin
      mutant. The production of hygroscopic biosurfactants on waxy leaf surfaces
      apparently benefits bacteria by both attracting moisture and facilitating access
      to nutrients. 

PMID- 24571679
TI  - Retrograde ureteroscopy via a continent urinary diversion: surgical techniques
      and common pitfalls.
AB  - PURPOSE: We assessed our experience performing retrograde ureteroscopy (URS) in
      patients with a continent urinary diversion. METHODS: A retrospective review was
      performed of patients with a continent urinary diversion necessitating URS for
      diagnostic or therapeutic purposes from 2002 to 2013. RESULTS: We identified 11
      male and 1 female patients with a continent urinary diversion with a mean age of
      62.5 years (27-77) who underwent 13 procedures on 17 renal units. Indication for
      URS was diagnostic in 10 (77%), stone disease in 2 (15%), and stricture in 1
      (8%). URS was attempted a median of 6.2 years (1.3-14.5) after diversion
      creation. Retrograde URS was attempted in 17 renal units with 10 (59%) accessed
      successfully. One procedure was staged with antegrade wire access obtained before
      retrograde URS. Inability to identify the afferent limb or ureteral orifice one
      (20%), tortuosity of afferent limb two (40%), angulation one (20%), and length of
      the afferent limb one (20%) were causes for unsuccessful retrograde URS. Of the
      successfully attempted retrograde URS, 75% occurred within the past 5 years.
      There were no complications in the successful retrograde URS group. Ureteral
      stents or nephrostomy tubes were left in place postprocedure in six (50%)
      patients. CONCLUSION: While technically challenging, retrograde URS can be
      performed successfully in patients with an orthotopic neobladder once the
      learning curve for the procedure is overcome.

PMID- 24571680
TI  - In situ quantification of living cell adhesion forces: single cell force
      spectroscopy with a nanotweezer.
AB  - A novel method is presented for in situ quantification of living cell adhesion
      forces using a homemade nanorobotic system provided with two independently
      actuated probes that form a dual-probe nanotweezer capable of pick-and-place
      manipulation of a single living cell in an aqueous environment. Compared with
      single-cell force spectroscopy (SCFS) based on traditional atomic force
      microscopy (AFM), cell immobilization via chemical trapping is unnecessary and
      the test cell can be efficiently released using the nanotweezer to significantly
      enhance production of the SCFS. Benefiting from the accurate force sensing
      capability of AFM, the nanotweezer allows reliable force measurement ranging from
      picoNewtons to microNewtons and is sufficiently sensitive to characterize short-
      and long-term adhesion of cell-cell and cell-substrate adhesions. Capabilities of
      the nanotweezer have been validated through experimental qualification of cell
      substrate and cell-cell adhesion events of C2C12 cells (mouse myoblast adherent)
      with different contact times. 

PMID- 24571681
TI  - Relationship between subjective and objective cognitive performance in multiple
      sclerosis.
AB  - OBJECTIVES: Self- and informant reports of patients' cognitive performance are an
      important source of information for clinicians to consider in neuropsychological
      evaluation. The aim of the study was to find out whether the relationship between
      subjective or informant observations of cognitive deterioration and objective
      cognitive performance differ in patients with relapsing and progressive multiple
      sclerosis (MS). MATERIALS & METHODS: One ninety-six MS patients (relapsing
      remitting n = 138; progressive n = 58) underwent neuropsychological assessment
      with the Brief Repeatable Battery of Neuropsychological Tests. Subjective and
      informant-reported cognitive symptoms, mood, impact of the disease, and quality
      of life were evaluated with self-reports. According to consistency of
      evaluations, patients and informants were classified as accurate estimators
      (consistent subjective and objective cognitive performance), underestimators
      (subjectively but not objectively cognitively impaired), or overestimators
      (objectively but not subjectively cognitively impaired). RESULTS: Patients' and
      informants' reports on patients' cognitive performance were approximately equally
      appropriate, slightly over half being accurate. Mood was associated with
      patients' subjective cognitive complaints. The relapsing group reported more
      subjective cognitive symptoms than the progressive group, although the objective
      cognitive performance did not differ between the groups. Overestimation occurred
      especially among patients with more severe physical disability, progressive
      phenotype of the disease, more pronounced cognitive impairment, and less
      education. CONCLUSIONS: Slightly over half of patient and informant observations
      of cognitive deterioration were appropriate. Patients with progressive phenotype
      were more prone to overestimation than patients with relapsing phenotype.

PMID- 24571682
TI  - Carboxybetaine methacrylate-modified nylon surface for circulating tumor cell
      capture.
AB  - Conventional in vitro circulating tumor cell (CTC) detection methods are always
      limited by blood sample volume because of the requirement of a large amount of
      blood. The aim of this study was to overcome the limitation by designing and
      making an in vivo CTC capture device. In this study, we designed and prepared a
      kind of proper material to serve the purpose of intervention. A method employing
      3-aminopropyltriethoxysilane (gamma-APS) as the coupling reagent to graft
      carboxybetaine methacrylate (CBMA) and to immobilize an anti-epithelial cell
      adhesion molecular (EpCAM) antibody on Nylon was developed. The results of X-ray
      photoelectron spectroscopy and Fourier transform infrared spectroscopy proved the
      successful graft of gamma-APS and CBMA to Nylon. Furthermore, the predicted
      improvement in the biocompatibilities of our modified Nylon was confirmed by
      water contact angle measurement, bovine serum albumin adhesion, platelet
      adhesion, plasma recalcification time determination, and cytotoxicity tests. The
      tumor cells adhesion experiment revealed that Nylon with the antibody immobilized
      on it had an affinity for EpCAM positive tumor cells higher than that of pristine
      Nylon. Additionally, the capture ability of the CTCs was demonstrated in a nude
      mouse tumor model using the interventional device made of the modified Nylon
      wire. The positive results suggest that CBMA-grafted and anti-EpCAM antibody
      immobilized Nylon is a promising new material for in vivo CTC capture devices. 

PMID- 24571683
TI  - Clinical outcomes associated with chronic antimicrobial suppression therapy in
      patients with continuous-flow left ventricular assist devices.
AB  - This retrospective cohort study evaluates the effect of chronic antimicrobial
      suppression (CAS) therapy on clinical outcomes in patients with continuous-flow
      left ventricular assist devices (CF-LVADs) and a history of device-related
      infection. Patients with CF-LVAD implantation between January 2008 and August
      2011 who received systemic CAS after index antibiotic treatment of a device
      related infection were included. Chronic suppression was defined as continuation
      of antibiotics for longer than 6 weeks after the index infection. Standard
      International Society for Heart and Lung Transplantation definitions were used.
      The primary outcome is failure of CAS, defined as a clinical deterioration
      resulting in the need for transition from oral to intravenous (IV) therapy or a
      need to change to a different IV antibiotic, elevation to status 1A on the
      transplant list as a result of ongoing infection, or device/driveline exchange.
      Of 140 patients screened, 16 patients were included (69% male, 63% African
      American, median age 52 years). The driveline was the most common site of
      infection (69%). Organisms isolated included Gram-positive cocci (n = 7), Gram
      negative bacilli (n = 10), and Candida (n = 1). Oral
      trimethoprim/sulfamethoxazole treatment was most commonly used for suppression
      (37.5%). Failure of CAS occurred in 5/16 (31%) patients after a mean time of 175
      days on therapy (range 10-598). The majority of failures (60%) required device
      exchanges. Side effects of nausea, vomiting, or diarrhea were reported in three
      patients; all required changes in oral suppression regimen. Clostridium difficile
      infection was noted in two patients. These results, which must be confirmed by a
      larger analysis, suggest that one-third of CF-LVAD patients may develop recurrent
      infections while on CAS therapy. 

PMID- 24571685
TI  - Post-Traumatic Endophthalmitis: A Mini-Review.
AB  - Post-traumatic endophthalmitis comprises 25-30% of all endophthalmitis cases.
      Post-traumatic endophthalmitis is an important clinical condition that may have
      serious anatomical and functional consequences. The type of pathogenic
      microorganism, nature of the injury, the presence of a foreign body, and the
      geographical region in which the trauma occurred are all important factors
      influencing both treatment and prognosis. Unlike postoperative endophthalmitis,
      there is not a confirmed treatment protocol recommended by the Endophthalmitis
      Vitrectomy Study Group in traumatic cases. In this study, we examine the
      incidence, risk factors, diagnosis, microbiological features, and treatment
      principles of post-traumatic endophthalmitis in order to guide clinicians who
      often encounter eye trauma related to this potential complication. 

PMID- 24571684
TI  - The Effect of Corneal Epithelium on Corneal Curvature in Patients with
      Keratoconus.
AB  - OBJECTIVE: To investigate the effects of corneal epithelium on corneal curvature
      in patients with keratoconus. DESIGN: This is a prospective, nonrandomized study.
      PARTICIPANTS: Fifty-nine eyes of 47 patients diagnosed as keratoconus and for
      whom corneal collagen crosslinking (CXL) was recruited in this study. METHODS:
      This study is a single-center clinical trial. Pregnancy, lactation, connective
      tissue disease, corneal thickness below 350 MUm, severe dry eyes, or scar of
      corneal surgery were exclusion criteria. Before and during CXL procedure after
      removing the corneal epithelium, maximum values of corneal apical curvature,
      simulated keratometry 1 (Sim-K1), simulated keratometry 2 (Sim-K2), temporal and
      inferior curvature values, all of which are 1.5 mm from the corneal center, were
      calculated. These values before and after removal of epithelium were compared
      statistically. RESULTS: Mean age of patients was 23.30 +/- 5.5 (12-38) years.
      Twenty-eight (59%) were male while 19 (41%) were female. Mean values measured
      before and after removing the corneal epithelium were: apical curvature; 59.19 +/
      7.2 (47.06-82.40) diopter (D) and 61.70 +/- 8.8 (49.19-92.66) D (p = 0.001),
      SimK1; 47.57 +/- 4.3 (39.14-64.57) D and 48.23 +/- 4.3 (41.89-66.70) D (p =
      0.001), SimK2; 52.04 +/- 5.3 (43.56-69.34) D and 53.34 +/- 5.6 (43.73-70.89) D (p
      = 0.001), inferior curvature; 53,85 +/- 5.2 (43.47-76.56) D and 55.05 +/- 5.8
      (44.56-81.93) D (p = 0.002), temporal curvature 49.49 +/- 5.1 (41.50-71.03) D and
      51.53 +/- 5.4 (41.58-73.34) D (p = 0.001), respectively. CONCLUSIONS: In
      keratoconus patients during CXL treatment, after removing the corneal epithelium,
      more steepness is detected in the curvature of the steeper area of the cornea.
      When evaluating patients with keratoconus, the masking effect of corneal
      epithelium on values of curvature should be taken into consideration.

PMID- 24571687
TI  - Vasovagal syncope and severe bradycardia following intranasal dexmedetomidine for
      pediatric procedural sedation.
AB  - We report syncope and bradycardia in an 11-year-old girl following administration
      of intranasal dexmedetomidine for sedation for a voiding cystourethrogram.
      Following successful completion of VCUG and a 60-min recovery period, the
      patient's level of consciousness and vital signs returned to presedation levels.
      Upon leaving the sedation area, the patient collapsed, with no apparent inciting
      event. The patient quickly regained consciousness and no injury occurred. The
      primary abnormality found was persistent bradycardia, and she was admitted to the
      hospital for telemetric observation. The bradycardia lasted ~2 h, and further
      cardiac workup revealed no underlying abnormality. Unanticipated and previously
      unreported outcomes may be witnessed as we expand the use of certain sedatives to
      alternative routes of administration.

PMID- 24571686
TI  - AKR1C3 overexpression may serve as a promising biomarker for prostate cancer
      progression.
AB  - BACKGROUND: Aldo-keto reductase family 1 member C3 (AKR1C3) is a key
      steroidogenic enzyme that is overexpressed in prostate cancer (PCa) and is
      associated with the development of castration-resistant prostate cancer (CRPC).
      The aim of this study was to investigate the correlation between the expression
      level of AKR1C3 and the progression of PCa. METHODS: Sixty human prostate needle
      biopsy tissue specimens and ten LNCaP xenografts from intact or castrated male
      mice were included in the study. The relationship between the level of AKR1C3
      expression by immunohistochemistry and evaluation factors for PCa progression,
      including prostate-specific antigen (PSA), Gleason score (GS) and age, were
      analyzed. RESULTS: Low immunoreactivity of AKR1C3 was detected in normal prostate
      epithelium, benign prostatic hyperplasia (BPH) and prostatic intraepithelial
      neoplasia (PIN). Positive staining was gradually increased with an elevated GS in
      PCa epithelium and LNCaP xenografts in mice after castration. The Spearman's r
      values (rs) of AKR1C3 to GS and PSA levels were 0.396 (P = 0.025) and -0.377 (P =
      0.036), respectively, in PCa biopsies. The rs of AKR1C3 to age was 0.76 (P =
      0.011). No statistically significant difference was found with other variables.
      CONCLUSION: Our study suggests that the level of AKR.1C3 expression is positively
      correlated with an elevated GS, indicating that AKR1C3 can serve as a promising
      biomarker for the progression of PCa. VIRTUAL SLIDES: The virtual slide(s) for
      this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/7748245591110149.

PMID- 24571689
TI  - The nature and evolutionary relationships of the earliest land plants.

PMID- 24571688
TI  - Association of apolipoprotein E polymorphism with maximal oxygen uptake after
      exercise training: a study of Chinese young adult.
AB  - BACKGROUND: Although a few studies have been conducted, it is still unclear
      whether the apolipoprotein E (APOE) polymorphism is associated with maximal
      oxygen uptake (VO(2max)) after exercise training. The objective of this study was
      to examine if the APOE gene polymorphisms affect VO(2max) after exercise training
      in Chinese young adult. METHODS: A total of 360 Chinese young adult (180 male and
      180 female) were recruited into this gender-specific cohorts. Anthropometrics,
      serum lipids, and VO(2max) were measured pre and post 6 months of supervised
      exercise training. Polymerase chain reaction restriction fragment length
      polymorphism (PCR-RFLP) assay was applied to assess the APOE gene polymorphisms.
      RESULTS: VO(2max) after exercise training increased significantly higher in
      carriers of E2/E3 in male [odds ratio (OR) =0.68, 95% confidence interval (CI) =
      0.04, 1.32; P = 0.04] and female (OR =0.62, 95% CI = 0.05, 1.18; P = 0.03).
      VO(2max) after exercise training increased significantly higher in carriers of
      E3/E4 in male (OR =0.60, 95% CI = 0.09, 1.11; P = 0.02) and female (OR =0.62, 95%
      CI = 0.09, 1.15; P = 0.02). No significant differences were found in carriers of
      E2/E2, E2/E4, E3/E3, E4/E4 in either male nor female. CONCLUSION: Our study found
      that APOE gene polymorphism was associated with VO(2max) levels after exercise
      training in Chinese young adult. In the future, further experiments will be
      necessary to confirm this finding and to find the possible mechanism.

PMID- 24571690
TI  - Being a facilitator can be costly: teasing apart reciprocal effects.

PMID- 24571691
TI  - The early bud gets to warm.

PMID- 24571692
TI  - Getting a sense for zinc in plants.

PMID- 24571693
TI  - Powdery mildew genomes reloaded.

PMID- 24571694
TI  - Drivers and dynamics of diversity in plant genomes.

PMID- 24571695
TI  - Fun, collaboration and formative assessment: skinquizition, a class wide gaming
      competition in a medical school with a large class.
AB  - BACKGROUND: Formative assessments are tools for assessing content retention,
      providing valuable feedback to students and teachers. In medical education,
      information technology-supported games can accommodate large classes divided into
      student teams while fostering active engagement. AIM: To establish an innovative
      stimulating approach to formative assessments for large classes furthering
      collaborative skills that promotes learning and student engagement linked to
      improvement of academic performance. METHODS AND RESULTS: Using audience response
      technology, a fast-paced, competitive, interactive quiz game involving
      dermatology was developed. This stimulating setting, provided on the last day of
      class, prepares students for high-stakes exams to continue their medical
      education while training collaborative skills as supported by survey outcomes and
      average class scores. SUMMARY AND CONCLUSIONS: Educational game competitions
      provide formative assessments and feedback for students and faculty alike,
      enhancing learning and teaching processes. In this study, we show an innovative
      approach to accommodate a large class divided into competing teams furthering
      collaborative skills reflected by academic performance.

PMID- 24571696
TI  - Taking research further still.

PMID- 24571697
TI  - Introduction. Stabilized stannous fluoride and dental erosion.

PMID- 24571699
TI  - Protective effects of SnF2 - Part II. Deposition and retention on pellicle-coated
      enamel.
AB  - Deposition of an acid-resistant barrier onto enamel represents a potentially
      superior means for delivering protection against dietary, erosive acid
      challenges. PURPOSE: The purpose of this study was to demonstrate the ability of
      a stabilised stannous fluoride (SnF2 ) dentifrice to: (1) deposit a SnF2 barrier
      layer onto pellicle-coated enamel surfaces; (2) increase the intensity of the
      barrier layer over time; and (3) be retained on the enamel surface for hours
      after product use. METHODS: Squares of human enamel were exposed to pooled saliva
      for 1 hour (pellicle formation) and separated into six sets. Set 1 was treated
      with the supernatant of a 1:3 slurry of the test dentifrice (Crest((r)) Pro
      Health((r)) : water for 2 minutes), then rinsed. Set 2 was treated in the same
      manner and then placed into saliva (6 hours). Set 3 was cycled through seven
      repeated treatments. Set 4 was treated for seven cycles and then placed into
      saliva (6 hours). Set 5 was a water control, and set 6 was a water control that
      remained in saliva for 6 hours. Surface analysis of specimens was done using
      laser ablation Inductively Coupled Plasma Mass Spectroscopy (ICP-MS). RESULTS:
      Deposition of a barrier layer was demonstrated, beginning with the initial
      treatment, with Sn (using isotopes (117) Sn + (120) Sn) measured on the enamel
      surface as the reference marker. Deposition of the barrier layer was greater
      after seven cycles, and the retention of this layer was highly significant (P =
      0.05, anova: 6 hours). CONCLUSIONS: This study confirms that: (1) the stabilised
      SnF2 dentifrice deposits a barrier layer onto the enamel surface, beginning with
      the first use of the product; (2) this barrier is enhanced following multiple
      treatments; and (3) the barrier layer is retained on the enamel surface for hours
      after product use.

PMID- 24571698
TI  - Protective effects of SnF2 - Part I. Mineral solubilisation studies on powdered
      apatite.
AB  - PURPOSE: To compare the ability of two active ingredients - sodium fluoride (NaF)
      and stannous fluoride (SnF2 ) - to inhibit hydroxyapatite (HAP) dissolution in
      buffered acidic media. METHODS: Two in vitro studies were conducted. HAP powder,
      which is representative of tooth mineral, was pretreated with: test solutions of
      NaF or SnF2 , 10 g solution per 300 mg HAP powder (Study 1); or NaF or SnF2
      dentifrice slurry supernatants, 20 g supernate per 200 mg HAP powder for 1 minute
      followed by three washes with water, then dried (Study 2). About 50 mg of
      pretreated HAP was exposed to 25 ml of acid dissolution media adjusted to and
      maintained at pH 4.5 in a Metrohn Titrino reaction cell. Exposure of HAP to the
      media results in dissolution and release of hydroxide ion, increasing the pH of
      the solution. The increase in pH is compensated for by automatic additions of
      acid to maintain the original pH (4.5) of the reaction cell. Total volume of
      titrant added after 30 minutes was used to calculate the percentage reduction in
      dissolution versus non-treated HAP control. RESULTS: Both F sources provided
      protection against acid dissolution; however, in each study, SnF2 -treated HAP
      was significantly more acid-resistant than the NaF treated mineral. In study 1,
      at 280 ppm F, representing concentrations of F found in the mouth after in vivo
      dentifrice use, the reduction in HAP dissolution was 47.7% for NaF and 75.7% for
      the SnF2 -treated apatite (extrapolated). In study 2, the reduction in HAP
      dissolution was 61.3% for NaF and 92.8% for SnF2 -treated samples. Differences in
      percentage reduction were statistically significant (Paired-t test). CONCLUSIONS:
      Results of these studies demonstrate that both of the fluoride sources tested
      enhance the acid resistance of tooth mineral and that resistance is significantly
      greater after treatment with SnF2 compared with treatment of tooth mineral with
      NaF.

PMID- 24571700
TI  - Protective effects of SnF2 - Part III. Mechanism of barrier layer attachment.
AB  - OBJECTIVE: To assess the ability of various fluoride salts to protect enamel
      against acid attack via a barrier mechanism. METHODS: Extracted human enamel
      specimens were cleaned and rinsed, then soaked in pooled human saliva for 1 hour
      to initiate formation of an early pellicle. Groups of three specimens each were
      etched for 10 minutes in 1% citric acid (pH 2.3), treated in a 1:3 slurry of
      dentifrice [1,100 ppm F as stannous fluoride (SnF2 ), 1,100 ppm F as sodium
      fluoride (NaF), 1,000 ppm F as sodium monofluorophosphate (SMFP), or 1,400 ppm F
      as amine fluoride (AmF)] and saliva for 2 minutes, exposed to 2% alizarin red-S
      (a calcium-selective dye) and rinsed again. The relative ability of each test
      product to deposit a barrier layer on the enamel surface was measured by its
      ability to protect against attachment of the calcium-selective dye. RESULTS:
      Specimens treated with the SnF2 dentifrice showed the least dye attachment,
      indicating a high level of surface protection. On a five-point scale, with 0
      being no dye deposition (100% protection) and four being complete dye coverage
      (0% protection), the SnF2 -treated specimens scored an average of 0.25, with NaF
      scoring 3.4, SMFP scoring 3.4 and AmF scoring 3.7. Protection of the enamel
      surface was significantly higher for the SnF2 product than for the other products
      (P < 0.05), with no significant differences among the other three F salts.
      CONCLUSIONS: These results demonstrate that after an aggressive acid challenge,
      SnF2 deposits a barrier layer onto the pellicle-coated enamel surface, and the
      barrier layer which attaches onto acid challenged tooth surfaces is different
      from any that might be provided by treatment with the other fluoride compounds
      tested.

PMID- 24571701
TI  - Erosion protection comparison of stabilised SnF2 , mixed fluoride active and
      SMFP/arginine-containing dentifrices.
AB  - PURPOSE: To investigate the relative erosion protection potential of marketed
      dentifrices formulated with either stabilised stannous fluoride (SnF2 ), sodium
      fluoride (NaF) and/or sodium monofluorophosphate (SMFP) using an established
      laboratory erosion cycling model. METHODS: Sound enamel cores from extracted,
      human enamel were cleaned, ground and polished, soaked in pooled saliva (pellicle
      formation) and treated with a 1:3 slurry of dentifrice and saliva. Specimens were
      subjected to daily challenges with 1% citric acid, a potentially damaging acid
      found in common food and drinks. Marketed dentifrices compared were: (1) a
      stabilised stannous fluoride product formulated with 1,100 ppm F as SnF2 ; (2) a
      cavity protection product containing 1,100 ppm F as NaF; (3) a cavity protection
      product comprising a mixed active fluoride system with 1,000 ppm F as SMFP + 450
      ppm F as NaF; and (4) a sensitivity product containing 1,450 ppm F as SMFP + 8%
      arginine bicarbonate. RESULTS: Specimens from Group 1 demonstrated an average
      loss of 5.5 (+/-1.2) MUm of tooth surface enamel; Groups 2, 3 and 4 lost an
      average of 18.3 (+/-0.9) MUm, 16.0 (+/-2.0) MUm and 17.1 (+/-1.1) MUm,
      respectively, of tooth surface enamel. Group 1 provided a statistically
      significant difference in protection compared with the other products.
      CONCLUSIONS: These results suggest that the marketed dentifrice formulated with
      stabilised SnF2 may provide enhanced protection of exposed tooth surfaces against
      dietary acid attack compared with the other products tested.

PMID- 24571702
TI  - Protective benefits of a stabilised stannous-containing fluoride dentifrice
      against erosive acid damage.
AB  - PURPOSE: To assess the potential of a stabilised stannous (Sn)-containing NaF
      dentifrice (Oral B/blend-a-Med((r)) Pro-Expert), in addition to a number of other
      marketed European dentifrices formulated with various fluoride actives and two
      control dentifrices, to protect enamel against erosive acid damage. METHODS:
      Cores of human enamel (four per group) were soaked in pooled human saliva, and
      then treated with a 1:3 slurry (dentifrice:saliva) using a standardised in vitro
      erosion model (5-day cycling) that includes 10-minute challenges with 1% citric
      acid applied 60 minutes after each dentifrice treatment. Enamel surface loss was
      measured using transverse microradiography (TMR). RESULTS: Specimens treated with
      the Sn-containing NaF dentifrice showed 6.5 MUm of surface loss +/- 1.2 (SEM),
      which was not significantly different (P < 0.05, Fisher LSD) from that of a
      clinically proven, stabilised SnF2 positive control [Crest((r)) Pro-Health, 1,100
      ppm F as SnF2 : 3.0 MUm of surface loss +/- 1.1 (SEM)]. The Sn-containing NaF
      dentifrice and the clinically proven positive control both provided significantly
      greater protection (P < 0.05, Fisher LSD) compared with all of the other products
      tested. Enamel loss (SEM) values for other European products and the reference
      control (active agents) were: Meridol((r)) : (1,400 ppm F as AmF + SnF2 ) 12.0
      MUm (1.47); Colgate((r)) Cavity Protection: (1,450 ppm F as SMFP + NaF) 12.9 MUm
      (1.66); Odol med 3((r)) (1,400 ppm F as NaF) 14.2 MUm (1.49); Elmex((r)) (1,400
      ppm F as AmF) 14.5 MUm (1.76); Colgate((r)) Enamel Protect: (1,450 ppm F as NaF +
      KNO3 ) 16.3 MUm (2.02); Lacalut((r)) aktiv: (1,400 ppm F as AlF3 ) 18.5 MUm
      (1.71); Sensodyne((r)) ProNamel(TM) : (1,450 ppm F as NaF + KNO3 ) 20.5 MUm
      (1.26); Crest Cavity Protection (1,100 ppm F as NaF, reference control) 22.00 MUm
      (2.04); and Mentadent((r)) : (1,450 ppm F as NaF + Zn citrate) 22.3 MUm (0.63).
      CONCLUSION: These results support the potential for the stabilised, Sn-containing
      NaF dentifrice to provide erosion protection benefits that are not significantly
      different from the positive control benchmark for erosion protection (stabilised
      SnF2 ), and are significantly better than a broad range of dentifrice
      formulations available on the European market.

PMID- 24571703
TI  - A randomised in situ trial, measuring the anti-erosive properties of a stannous
      containing sodium fluoride dentifrice compared with a sodium fluoride/potassium
      nitrate dentifrice.
AB  - OBJECTIVES: To determine if a stabilised, stannous-containing sodium fluoride
      dentifrice provides greater enamel protection in situ against intraoral dietary
      erosive challenges compared with a sodium fluoride/potassium nitrate dentifrice.
      METHODS: A single-centre, investigator blind, randomised, supervised, two
      treatment, non-brushing, four-period crossover in situ study was undertaken, with
      each test period being 15 days. Thirty-five healthy adult subjects were recruited
      to participate in the study, which included four erosive acid challenges per day.
      Subjects were randomised to product treatment, which included either: (1) a
      stannous-containing sodium fluoride dentifrice (Oral-B((r)) Pro-Expert Sensitive)
      or (2) a sodium fluoride/potassium nitrate dentifrice (Sensodyne((r))
      Pronamel((r)) ). Each study subject wore an intraoral appliance retaining two
      sterilised, polished human enamel samples for 6 hours/day. Subjects swished with
      an allocated dentifrice slurry twice a day and with 250 ml of orange juice for 10
      minutes (25 ml/minute over a 10-minute period) four times per day. The primary
      and secondary outcomes for this study were enamel loss measured using contact
      profilometry at days 15 and 5, respectively, using parametric analysis methods.
      RESULTS: At day 15, a 38% lower enamel loss (P < 0.0001) was observed, with
      estimated medians of 2.03 MUm (SE 0.247) and 3.30 MUm (SE 0.379), in favour of
      the stannous-containing dentifrice. At day 5, specimens treated with the stannous
      containing sodium fluoride dentifrice demonstrated 25% less enamel loss than
      those treated with the sodium fluoride/potassium nitrate dentifrice. Treatment
      differences at day 5 were also statistically significant (P < 0.05), with
      estimated medians of 1.37 MUm (SE 0.177) and 1.83 MUm (SE 0.223), respectively.
      CONCLUSIONS: Results of this in situ study suggest the stabilised, stannous
      containing sodium fluoride dentifrice could be used to provide significantly
      greater protection to enamel from erosive acid challenge compared with that
      provided by conventional fluoride-containing products.

PMID- 24571704
TI  - In situ clinical evaluation of a stabilised, stannous fluoride dentifrice.
AB  - OBJECTIVES: To compare the erosion protection efficacy of a stabilised, stannous
      fluoride (SnF2 ) dentifrice versus a sodium fluoride (NaF) dentifrice using a
      modified in situ clinical model. METHODS: This study, a randomised parallel group
      in situ design with in vivo product use and ex vivo acid challenge, compared: A,
      a dentifrice containing 1,450 ppm F as NaF; B, a dentifrice containing 1,450 ppm
      F (1,100 ppm F as SnF2 + 350 ppm F as NaF); and T, tap water. Sample size was n =
      4 per group (total of 12 subjects) and within each subject appliances were placed
      on each side of the mouth (left and right). Enamel specimens were placed in
      different positions of the mouth (front, mid-front, mid-rear, rear) in each
      appliance (total = 8 specimens per subject). Product treatment was twice per day
      (lingual brushing for 30 seconds followed by swishing for 90 seconds with the
      resultant product/saliva slurry) in vivo for 15 days, and ex vivo acid treatment
      (0.02 m citric acid 5 minutes four times per day; total exposure time = 300
      minutes). Data were analysed using a general linear repeated measures model with
      treatment, side and position as fixed effects. Within subjects, correlations were
      modelled assuming a different correlation and variance for treatment B relative
      to the other groups. Pairwise treatment differences were performed using a 5% two
      sided significance level. RESULTS: Enamel loss (in MUm) was significantly lower
      (P < 0.005) for treatment B versus treatments A and T. Treatment B reduced enamel
      surface loss by 86.9% relative to treatment A. There was no statistical
      difference in mean enamel loss (P = 0.51) between treatments A and T. Enamel loss
      was not statistically different for side (left vs. right; P = 0.44) or position
      (front, mid-front, mid-rear, rear; P = 0.36). CONCLUSION: This modified in situ
      erosion model confirmed the enhanced erosion protection benefits of a stabilised
      SnF2 dentifrice versus a conventional NaF dentifrice, validating the ability of
      the model to safely and effectively demonstrate differences in the erosion
      protection potential of oral care products.

PMID- 24571706
TI  - Efficient, uniform, and large area microwave magnetic coupling to NV centers in
      diamond using double split-ring resonators.
AB  - We report on the development and utilization of a double split-ring microwave
      resonator for uniform and efficient coupling of microwave magnetic field into
      nitrogen-vacancy (NV) centers in a diamond over a mm(2) area. Uniformity and
      magnitude of delivered microwave field were measured using the Rabi nutation
      experiment on arrays of diamond nanowires with ensemble NV centers. An average
      Rabi nutation frequency of 15.65 MHz was measured over an area of 0.95 * 1.2 mm,
      for an input microwave power of 0.5 W. By mapping the Rabi nutation frequency to
      the magnetic field, the average value of the magnetic field over the
      aforementioned area and input microwave power was 5.59 G with a standard division
      of 0.24 G. 

PMID- 24571705
TI  - Feasibility study for early supported discharge in adults with respiratory
      infection in the UK.
AB  - BACKGROUND: Many patients with pneumonia and lower respiratory tract infection
      that could be treated as outpatients according to their clinical severity score,
      are in fact admitted to hospital. We investigated whether, with medical and
      social input, these patients could be discharged early and treated at home.
      OBJECTIVES: (1) To assess the feasibility of providing an early supported
      discharge scheme for patients with pneumonia and lower respiratory tract
      infection (2) To assess the patient acceptability of a study comprising of
      randomisation to standard hospital care or early supported discharge scheme.
      METHODS:  DESIGN: Randomised controlled trial. SETTING: Liverpool, UK. Two
      University Teaching hospitals; one city-centre, 1 suburban in Liverpool, a city
      with high deprivation scores and unemployment rates. PARTICIPANTS: 200 patients
      screened: 14 community-dwelling patients requiring an acute hospital stay for
      pneumonia or lower respiratory tract infection were recruited. INTERVENTION:
      Early supported discharge scheme to provide specialist respiratory care in a
      patient's own home as a substitute to acute hospital care. MAIN OUTCOME MEASURES:
      Primary - patient acceptability. Secondary - safety/mortality, length of hospital
      stay, readmission, patient/carer (or next of kin) satisfaction, functional status
      and symptom improvement. RESULTS: 42 of the 200 patients screened were eligible
      for early supported discharge; 10 were only identified at the point of discharge,
      18 declined participation and 14 were randomised to either early supported
      discharge or standard hospital care. The total hospital length of hospital stay
      was 8.33 (1-31) days in standard hospital care and 3.4 (1-7) days in the early
      supported discharge scheme arm. In the early supported discharge scheme arm
      patient carers reported higher satisfaction with care and there were less
      readmissions and hospital-acquired infections. LIMITATIONS: A small study in a
      single city. This was a feasibility study and therefore not intended to compare
      outcome data. CONCLUSIONS: An early supported discharge scheme for patients with
      pneumonia and lower respiratory tract infection was feasible. Larger numbers of
      patients would be eligible if future work included patients with dementia and
      those residing in care homes. TRIAL REGISTRATION: ISRCTN25542492.

PMID- 24571707
TI  - Phenolic acids, hydrolyzable tannins, and antioxidant activity of geopropolis
      from the stingless bee Melipona fasciculata Smith.
AB  - Geopropolis is a mixture of plant resins, waxes, and soil produced by the
      stingless bee Melipona fasciculata Smith. This paper describes the antioxidant
      activity and chemical composition of geopropolis produced by M. fasciculata. The
      total phenolic content determined with the Folin-Ciocalteu reagent was highest in
      the ethyl acetate fraction and hydroalcoholic extract. Antioxidant activity was
      assayed by the in vitro DPPH, ABTS, and FRAP assays. The hydroalcoholic extract
      and fractions of geopropolis, except for the hexane fraction, exhibited
      antioxidant activity against DPPH, ABTS, and FRAP. The phenolic compounds were
      identified by HPLC-DAD-MS on the basis of the evaluation of their UV-vis
      absorption maxima (lambdamax) and mass spectral analysis. Eleven compounds
      belonging to the classes of phenolic acids and hydrolyzable tannins (gallotannins
      and ellagitannins) were tentatively identified. These compounds are responsible
      for the antioxidant activity and high phenolic content of geopropolis produced by
      M. fasciculata. 

PMID- 24571708
TI  - Coarse-grained modeling of the titration and conductance behavior of aqueous
      fullerene hexa malonic acid (FHMA) solutions.
AB  - The coarse-grained continuum primitive model is developed and used to
      characterize the titration and electrical conductance behavior of aqueous
      solutions of fullerene hexa malonic acid (FHMA). The spherical FHMA molecule, a
      highly charged electrolyte with an absolute valence charge as large as 12, is
      modeled as a dielectric sphere in Newtonian fluid, and electrostatics are treated
      numerically at the level of the non-linear Poisson-Boltzmann equation. Transport
      properties (electrophoretic mobilities and conductances) of the various charge
      states of FHMA are numerically computed using established numerical algorithms.
      For reasonable choices of the model parameters, good agreement between experiment
      (published literature) and modeling is achieved. In order to accomplish this,
      however, a moderate degree of specific binding of principal counterion and FHMA
      must be included in the modeling. It should be emphasized, however, that
      alternative explanations are possible. This comparison is made at 25  degrees C
      for both Na(+) and Ca(2+) principal counterions. The model is also used to
      characterize the different charge states and degree of counterion binding to
      those charge states as a function of pH. 

PMID- 24571709
TI  - A new cyclopeptide with antifungal activity from the co-culture broth of two
      marine mangrove fungi.
AB  - A new cyclic tetrapeptide, cyclo-(L-leucyl-trans-4-hydroxy-L-prolyl-D-leucyl
      trans-4-hydroxy-L-proline) (1), was isolated from the co-culture broth of two
      mangrove fungi Phomopsis sp. K38 and Alternaria sp. E33. The structure of 1 was
      determined by analysis of spectroscopic data and Marfey's analytic method.
      Primary bioassay demonstrated that compound 1 exhibited moderate to high
      inhibitory activity against four crop-threatening fungi including Gaeumannomyces
      graminis, Rhizoctonia cerealis, Helminthosporium sativum and Fusarium graminearum
      as compared with triadimefon.

PMID- 24571710
TI  - Currarino syndrome in an adult presenting with a presacral abscess: a case
      report.
AB  - INTRODUCTION: Currarino syndrome (Currarino triad) was described in 1981 as a
      triad syndrome with a common embryogenesis in infants and with three
      characteristics: anorectal stenosis, a defect in the sacral bone, and a presacral
      mass. We describe here an unusual case of Currarino syndrome in an adult
      presenting with a presacral abscess but no meningitis. CASE PRESENTATION: A 32
      year-old Japanese man presented with fever, arthralgia and buttock pain. A
      digital rectal examination showed mild rectal stenosis with local warmth and
      tenderness in the posterior wall of his rectum. Computed tomography showed a
      scimitar-shaped deformity of his sacrum and an 8cm presacral mass, which
      continued to a pedicle of his deformed sacrum. This was diagnosed as Currarino
      syndrome with a presacral abscess. The abscess was drained by a perianal approach
      with our patient treated with antibiotics. His symptoms soon disappeared. After
      three months, an excision was performed through a posterior sagittal approach.
      His postoperative course was uneventful and he was discharged 10 days after
      surgery. A histopathological examination revealed an infected epidermoid cyst. He
      has been free from recurrence as of four years and six months after surgery.
      CONCLUSIONS: We report a case of Currarino syndrome in an adult who presented
      with a presacral abscess but no meningitis. Abscess drainage followed by radical
      surgery resulted in a successful outcome.

PMID- 24571711
TI  - Epigenetic silencing of miR-375 induces trastuzumab resistance in HER2-positive
      breast cancer by targeting IGF1R.
AB  - BACKGROUND: Resistance to humanized monoclonal erbB2/HER2 antibody, trastuzumab
      (Herceptin), has become a pivotal obstacle for targeted therapy of HER2-positive
      breast cancers. The activation of alternative growth factor receptors, in
      particular, the insulin-like growth factor 1 receptor (IGF1R), represents a
      common feature of trastuzumab-refractory cells; however, the underlying mechanism
      remains elusive. METHODS: Trastuzumab-resistant breast cancer SKBr-3 cells were
      generated by long-term in vitro culture of SKBr-3 cells in the presence of
      trastuzumab. Among the differentially expressed microRNAs (miRNAs) screened by
      microarray analysis, candidate miRNA(s) predicted to target IGF1R was studied for
      its role in conferring trastuzumab resistance. The mechanism underlying decreased
      expression of IGF1R-targeted miRNA in refractory cells was also addressed.
      RESULTS: miR-375, which was downregulated and predicted to target IGF1R in
      trastuzumab-resistant HER2-positive breast cancer cells, could indeed inhibit the
      cellular luciferase activity in a reporter construct containing the 3'-UTR of
      IGF1R. Overexpression of miR-375 restored the sensitivity of cells to
      trastuzumab, while inhibition of miR-375 conferred trastuzumab resistance on HER2
      positive breast cancer cells. Blockade of DNA methylation and histone
      deacetylation restored the expression of miR-375 in trastuzumab-resistant cells.
      A reverse correlation between the levels of miR-375 and IGF1R was validated in
      clinical breast cancers. CONCLUSIONS: Epigenetic silencing of miR-375 causes the
      upregulation of IGF1R, which at least partially underlies trastuzumab resistance
      of breast cancer cells. Our study has implications for miR-375 as a potential
      target in combination with trastuzumab for treating HER2-positive breast cancers.

PMID- 24571712
TI  - Adaptation of Bacillus subtilis carbon core metabolism to simultaneous nutrient
      limitation and osmotic challenge: a multi-omics perspective.
AB  - The Gram-positive bacterium Bacillus subtilis encounters nutrient limitations and
      osmotic stress in its natural soil ecosystem. To ensure survival and sustain
      growth, highly integrated adaptive responses are required. Here, we investigated
      the system-wide response of B. subtilis to different, simultaneously imposed
      stresses. To address the anticipated complexity of the cellular response
      networks, we combined chemostat experiments under conditions of carbon
      limitation, salt stress and osmoprotection with multi-omics analyses of the
      transcriptome, proteome, metabolome and fluxome. Surprisingly, the flux through
      central carbon and energy metabolism is very robust under all conditions studied.
      The key to achieve this robustness is the adjustment of the biocatalytic
      machinery to compensate for solvent-induced impairment of enzymatic activities
      during osmotic stress. Specifically, increased production of several enzymes of
      central carbon metabolism compensates for their reduced activity in the presence
      of high salt. A major response of the cell during osmotic stress is the
      production of the compatible solute proline. This is achieved through the
      concerted adjustment of multiple reactions around the 2-oxoglutarate node, which
      drives metabolism towards the proline precursor glutamate. The fine-tuning of the
      transcriptional and metabolic networks involves functional modules that overarch
      the individual pathways. 

PMID- 24571713
TI  - Standardization of patient outcomes reporting in percutaneous nephrolithotomy.
AB  - BACKGROUND AND PURPOSE: There exist no global standards for defining patient
      outcomes in renal stone surgery. The objective of this study was to evaluate the
      quality of reporting of outcomes in studies investigating percutaneous
      nephrolithotomy (PCNL) and to propose standardized consensus definitions for
      common outcomes. METHODS: We performed a literature search in PubMed for
      randomized controlled studies that investigated PCNL between 2002 and 2012. All
      outcomes reported were analyzed for each study. Each article was examined to
      identify the definition of each reported patient outcome. Various aspects of
      patient outcomes were presented to a panel of 85 experts in a Delphi process
      consisting of three rounds. The experts were asked to select options that they
      believed would best describe each outcome. Finally, we composed recommendations
      for definition of the most common outcomes reported in PCNL studies. RESULTS:
      Eighty-three RCTs were included in the review of patient outcomes. Stone-free
      rate (55, 63.9%), length of stay (47, 56.6%), complication rate (44, 53.0%), and
      changes in hemoglobin (40, 48.2%) were the most frequently reported outcomes in
      randomized controlled trials of PCNL. Only 24/53 (45.3%) studies had a formal
      definition of stone-free status. Only 31/40 (77.5%) studies, which reported
      change in hemoglobin, had a unit of measurement; however, 22/40 (55.0%) did not
      report the timing of postoperative hemoglobin measurement. A set of
      recommendations for defining patient outcomes in PCNL is presented for the 15
      most commonly reported outcomes in PCNL. CONCLUSIONS: Wide variations and
      underspecification exist in the definition and reporting of outcomes in PCNL. We
      propose recommendations for the definition of outcomes based on a review of the
      literature and expert opinion. Standardization of outcome definition and
      reporting will improve the quality of urologic research.

PMID- 24571715
TI  - Using imputation and mixture model approaches to integrate multi-state capture
      recapture models with assignment information.
AB  - In this article, we first extend the superpopulation capture-recapture model to
      multiple states (locations or populations) for two age groups., Wen et al.,
      (2011; 2013) developed a new approach combining capture-recapture data with
      population assignment information to estimate the relative contributions of in
      situ births and immigrants to the growth of a single study population. Here, we
      first generalize Wen et al., (2011; 2013) approach to a system composed of
      multiple study populations (multi-state) with two age groups, where an imputation
      approach is employed to account for the uncertainty inherent in the population
      assignment information. Then we develop a different, individual-level mixture
      model approach to integrate the individual-level population assignment
      information with the capture-recapture data. Our simulation and real data
      analyses show that the fusion of population assignment information with capture
      recapture data allows us to estimate the origination-specific recruitment of new
      animals to the system and the dispersal process between populations within the
      system. Compared to a standard capture-recapture model, our new models improve
      the estimation of demographic parameters, including survival probability,
      origination-specific entry probability, and especially the probability of
      movement between populations, yielding higher accuracy and precision.

PMID- 24571714
TI  - Assessing tissue damage in multiple sclerosis: a biomarker approach.
AB  - OBJECTIVES: Magnetic resonance imaging (MRI) of the brain and spinal cord is the
      gold standard for assessing disease activity in multiple sclerosis (MS). MRI is
      an excellent instrument for determination of accumulated damage to the brain and
      spinal cord, but tells us little about ongoing tissue damage. In this study,
      biomarkers of oligodendrocyte, axonal and astrocyte injury were related to MRI
      and clinical findings and used to assess tissue damage in MS. MATERIALS AND
      METHODS: Cerebrospinal fluid from 44 patients with relapsing-remitting MS, 20
      with secondary progressive MS and 15 controls were investigated with ELISA to
      determine levels of myelin basic protein (MBP), neurofilament light (NFL) and
      glial fibrillary acidic protein (GFAp). Patients underwent MRI of the brain and
      spinal cord, and gadolinium enhancing lesions, T1 lesions and T2 lesions were
      counted. RESULTS: Patients in clinical relapse and patients with nonsymptomatic
      gadolinium enhancing lesions had high levels of MBP and NFL, indicating ongoing
      damage to oligodendrocytes and axons. The level of MBP dropped quickly within a
      week from the onset of a relapse, whereas NFL remained elevated for several weeks
      and GFAp slowly rose during the course of a relapse. Relapsing-remitting MS
      patients without gadolinium enhancing lesions had values of MBP, NFL and GFAp
      similar to controls, while patients with secondary progressive disease had
      moderately increased values of all biomarkers. CONCLUSIONS: Analysis of MBP, NFL
      and GFAp provides direct means to measure tissue damage and is a useful addition
      to our methods for evaluation of MS.

PMID- 24571716
TI  - Blastic plasmacytoid dendritic cell neoplasm: the first report of two cases
      treated by 5-azacytidine.
AB  - Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic
      malignancy which was first included as an independent cutaneous lymphoma in the
      2008 World Health Organisation (WHO) classification (1). BPDCN usually has an
      extremely poor prognosis, with quick relapses after chemotherapy (2; 3). Here, we
      report two cases of patients diagnosed in 2011 with BPDCN and myelodysplasia, and
      who were treated for the first time with 5-azacytidine (5-Aza); a drug approved
      by the Food and Drug Administration (FDA) and mainly used in the treatment of
      myelodysplastic syndrome (Kaminskas E, et al. 2005 Clin Cancer Res, 11, 3604-8).
      The first case was an 81-year-old man who presented with unusual CD10+, CD56-
      immunohistochemistry and 45X, -Y abnormality using fluorescent in situ
      hybridization (FISH) analysis. The second case was a 78-year-old woman who
      manifested monosomy 13 and chromosome instability due to D13S319 locus deletion
      in 13q14 as determined by FISH. Both patients showed excellent responses of their
      skin lesions after one cycle of chemotherapy, and their hematological disease was
      stabilized; however, pulmonary sepsis set in, followed by neutropenia after the
      fourth and the fifth cycle of treatment, that is, eight and 9 months
      postdiagnosis, respectively, leading to patient death.

PMID- 24571718
TI  - Blue-emitting copper nanoclusters synthesized in the presence of lysozyme as
      candidates for cell labeling.
AB  - Highly fluorescent copper nanoclusters (Cu NCs) have been synthesized using
      single-step reduction of copper sulfate by hydrazine in the presence of lysozyme.
      The fluorescence quantum yield was measured to be as high as 18%. The emission
      was also found to be dependent on the excitation wavelength. Mass spectrometric
      analyses indicated the presence of species corresponding to Cu2 to Cu9.
      Transmission electron microscopic analyses indicated the formation of
      agglomerated particles of average diameter of 2.3 nm, which were constituted of
      smaller particles of average diameter of 0.96 nm. They were found to be stable
      between pH 4 and 10 and in addition having excellent chemical and photostability.
      The noncytotoxic NCs were used to successfully label cervical cancer HeLa cells. 

PMID- 24571719
TI  - On the use of fixed-intensity functional electrical stimulation for attenuating
      essential tremor.
AB  - A great proportion of essential tremor (ET) patients have not so far been able to
      receive functional benefits from traditional therapies. In this regard, the use
      of functional electrical stimulation (FES) has been proposed for reducing tremor
      amplitude by stimulating muscles in antiphase with respect to the trembling
      motion. Although some studies have reported success in terms of tremor
      attenuation, drawbacks still exist that prevent the method from being used in
      real-life applications. In this article, we explore an alternative approach: a
      strategy based on the hypothesis that FES-induced constant muscle contraction may
      provide functional benefit for tremor patients. To evaluate the proposed
      strategy, experiments were conducted in which stimulation was intermittently
      turned on and off while the subjects performed a static motor task. The results
      of the proposed experimental protocol indicate that tremor attenuation using this
      strategy is feasible, as consistent tremor attenuation levels were obtained in
      eight out of 10 ET patients. Nonetheless, tremor reduction was not instantaneous
      for all successful trials, indicating that prior training with FES may improve
      the overall response. Furthermore, although simpler assistive devices may
      potentially be designed based on this technique, some experimental difficulties
      still exist, which suggests that further studies are necessary.

PMID- 24571717
TI  - Nature and biosynthesis of galacto-oligosaccharides related to oligosaccharides
      in human breast milk.
AB  - Human milk oligosaccharides (HMO) are prominent among the functional components
      of human breast milk. While HMO have potential applications in both infants and
      adults, this potential is limited by the difficulties in manufacturing these
      complex structures. Consequently, functional alternatives such as galacto
      oligosaccharides are under investigation, and nowadays, infant formulae are
      supplemented with galacto-oligosaccharides to mimic the biological effects of
      HMO. Recently, approaches toward the production of defined human milk
      oligosaccharide structures using microbial, fermentative methods employing
      single, appropriately engineered microorganisms were introduced. Furthermore,
      galactose-containing hetero-oligosaccharides have attracted an increasing amount
      of attention because they are structurally more closely related to HMO. The
      synthesis of these novel oligosaccharides, which resemble the core of HMO, is of
      great interest for applications in the food industry. 

PMID- 24571720
TI  - Results from screening immigrants of low-income countries: data from a public
      primary health care.
AB  - BACKGROUND: A total of 3,132 immigrants from low- and middle-income countries
      were involved in a cross-sectional observational study to screen for infectious
      diseases among immigrants attending public primary health care (PHC) centers. The
      study was conducted to clarify the degree of demographic differences and risk
      predictors of these diseases. METHODS: Demographic and clinical variables,
      screening for infectious diseases [hepatitis B and C, human immunodeficiency
      virus infection, syphilis, and tuberculosis (TB)], and analytical data (anemia,
      hematuria, and liver function) were recorded from immigrants attending a public
      PHC unit in Barcelona. RESULTS: Global hepatitis B, including chronic and
      previous, reached 18.1%; Morocco as the country of origin [odds ratio (OR) 2.1,
      95% confidence interval (CI) 1.07-4.14] and gastrointestinal symptoms (OR 1.9, CI
      1.18-3.02) were risk factors. Hepatitis C prevalence was 3.3% with elevated
      hepatic transaminase levels as a risk factor (OR 26.1, CI 8.68-78.37). Positive
      syphilis was 3.1%; latent and active TB rates were 28.1 and 5.8%, respectively.
      Concerning TB, we found remarkable differences both among WHO regions of origin
      (the Eastern Mediterranean region showed the highest rate of active TB, 8%) and
      the three categories of years of residence in Spain (6.5% for <1 year, 12.8% for
      1-5 years, and 10% for >5 years). CONCLUSIONS: The data allowed recommendation of
      a minimal screening of TB in immigrants from low-income countries regardless of
      the years of residence in Spain, hepatitis C in patients with altered
      transaminase levels, and hepatitis B in patients with gastrointestinal symptoms
      and/or from Morocco.

PMID- 24571721
TI  - Pathogenesis of Vernal Keratoconjunctivitis and Associated Factors.
AB  - AIM: To investigate the role of some variables, including allergy and
      autoimmunity, in the pathogenesis of vernal keratoconjunctivitis (VKC). The VKC
      is a chronic and often severe form of bilateral keratoconjunctivitis. Usually, it
      begins during the first decade and disappears during the end of the second decade
      of life. MATERIALS AND METHODS: 26 patients with VKC were selected. The diagnosis
      was performed by the ophthalmologist through a score based on ocular signs and
      subjective symptoms before and after administration of 1% cyclosporine A (Cy)
      eyedrops. Each variable was graded: 0 = absent; 1 = mild; 2 = moderate; 3 =
      severe. Patients with a total score >=7 were included in the study. Blood samples
      were collected at the initial time for the determination of autoimmunity by total
      IgE and antinuclear antibodies (ANA). A Skin Prick Test (SPT) was performed on
      each patient to common inhalants and food allergens. RESULTS: 53.8% of the
      children resulted atopic. The most important allergens were house dust mites and
      grasses. 46.1% of the patients showed total IgE >100 UI/ml and 30.8% had ANA
      positivity at the first determination. The photophobia occurred in 42.3% of
      children, most frequently with respect to other symptoms like secretion or
      tearing (30.8%), foreign body sensation (15.4%), itching and conjunctival
      hyperemia (11.5%). CONCLUSIONS: Fortunately all children improved their symptoms
      after Cy eyedrop therapy. Moreover, there was an elevated percentage (30.8%) of
      children with ANA positivity compared with the values in the general pediatric
      population. Despite the fact that it is a non-specific autoantibody, its high
      presence in a population of children with VKC may have an important role in
      clarifying etiopathogenesis and chronic inflammation.

PMID- 24571722
TI  - Rapid bioassay to measure early reactive oxygen species production in Arabidopsis
      leave tissue in response to living Pseudomonas syringae.
AB  - BACKGROUND: Arabidopsis thaliana and Pseudomonas syringae pathovar tomato (Pto)
      provide an excellent plant-bacteria model system to study innate immunity. During
      pattern-triggered immunity (PTI), cognate host receptors perceive pathogen
      associated molecular patterns (PAMPs) as non-self molecules. Pto harbors many
      PAMPs; thus for experimental ease, many studies utilize single synthesized PAMPs
      such as flg22, a short protein peptide derived from Pseudomonas flagellin. Flg22
      recognition by Arabidopsis Flagellin Sensing 2 (FLS2) initiates a plethora of
      signaling responses including rapid production of apoplastic reactive oxygen
      species (ROS). Assessing flg22-ROS has been instrumental in identifying novel
      PAMP-signaling components; but comparably little is known whether in Arabidopsis,
      ROS is produced in response to intact live Pto and whether this response can be
      used to dissect genetic requirements of the plant host and live bacterial
      pathogens in planta. RESULTS: Here, we report of a fast and robust bioassay to
      quantitatively assess early ROS in Arabidopsis leaves, a tissue commonly used for
      pathogen infection assays, in response to living bacterial Pto strains. We
      establish that live Pto elicits a transient and dose-dependent ROS that differed
      in timing of initiation, amplitude and duration compared to flg22-induced ROS.
      Our control experiments confirmed that the detected ROS was dependent on the
      presence of the bacterial cells. Utilizing Arabidopsis mutants previously shown
      to be defective in flg22-induced ROS, we demonstrate that ROS elicited by live
      Pto was fully or in part dependent on RbohD and BAK1, respectively. Because fls2
      mutants did not produce any ROS, flagellin perception by FLS2 is the predominant
      recognition event in live Pto-elicited ROS in Arabidopsis leaves. Furthermore
      using different Pto strains, our in planta results indicate that early ROS
      production appeared to be independent of the Type III Secretion System.
      CONCLUSIONS: We provide evidence and necessary control experiments demonstrating
      that in planta, this ROS bioassay can be utilized to rapidly screen different
      Arabidopsis mutant lines and ecotypes in combination with different bacterial
      strains to investigate the genetic requirements of a plant host and its pathogen.
      For future experiments, this robust bioassay can be easily extended beyond
      Arabidopsis-Pto to diverse plant-pathosystems including crop species and their
      respective microbial pathogens.

PMID- 24571723
TI  - The calculus of cures.

PMID- 24571725
TI  - PRKACB and Carney complex.

PMID- 24571724
TI  - Constitutive activation of PKA catalytic subunit in adrenal Cushing's syndrome.
AB  - BACKGROUND: Corticotropin-independent Cushing's syndrome is caused by tumors or
      hyperplasia of the adrenal cortex. The molecular pathogenesis of cortisol
      producing adrenal adenomas is not well understood. METHODS: We performed exome
      sequencing of tumor-tissue specimens from 10 patients with cortisol-producing
      adrenal adenomas and evaluated recurrent mutations in candidate genes in an
      additional 171 patients with adrenocortical tumors. We also performed genomewide
      copy-number analysis in 35 patients with cortisol-secreting bilateral adrenal
      hyperplasias. We studied the effects of these genetic defects both clinically and
      in vitro. RESULTS: Exome sequencing revealed somatic mutations in PRKACA, which
      encodes the catalytic subunit of cyclic AMP-dependent protein kinase (protein
      kinase A [PKA]), in 8 of 10 adenomas (c.617A->C in 7 and c.595_596insCAC in 1).
      Overall, PRKACA somatic mutations were identified in 22 of 59 unilateral adenomas
      (37%) from patients with overt Cushing's syndrome; these mutations were not
      detectable in 40 patients with subclinical hypercortisolism or in 82 patients
      with other adrenal tumors. Among 35 patients with cortisol-producing
      hyperplasias, 5 (including 2 first-degree relatives) carried a germline copy
      number gain (duplication) of the genomic region on chromosome 19 that includes
      PRKACA. In vitro studies showed impaired inhibition of both PKA catalytic subunit
      mutants by the PKA regulatory subunit, whereas cells from patients with germline
      chromosomal gains showed increased protein levels of the PKA catalytic subunit;
      in both instances, basal PKA activity was increased. CONCLUSIONS: Genetic
      alterations of the catalytic subunit of PKA were found to be associated with
      human disease. Germline duplications of this gene resulted in bilateral adrenal
      hyperplasias, whereas somatic PRKACA mutations resulted in unilateral cortisol
      producing adrenal adenomas. (Funded by the European Commission Seventh Framework
      Program and others.).

PMID- 24571727
TI  - Cyclic carbo-isosteric depsipeptides and peptides as a novel class of
      peptidomimetics.
AB  - A novel and highly efficient cyclization method has been developed to access a
      new class of cyclic carbo-isosteric depsipeptides and carbo-isosteric peptides.
      Our strategy requires easily accessible C-terminal methyl ketone ester or amide
      functionalized linear precursors as starting materials. The well-known reductive
      amination has then been used to afford cyclic tetra- to octa-pseudopeptides via a
      selective intramolecular formation of a glycine peptidomimetic unit under
      moderate dilution. 

PMID- 24571726
TI  - Increased longitudinal contractility and diastolic function at rest in well
      trained amateur Marathon runners: a speckle tracking echocardiography study.
AB  - BACKGROUND: Regular physical activity reduces cardiovascular risk. There is
      concern that Marathon running might acutely damage the heart. It is unknown to
      what extent intensive physical endurance activity influences the cardiac
      mechanics at resting condition. METHODS: Eighty-four amateur marathon runners (43
      women and 41 men) from Berlin-Brandenburg area who had completed at least one
      marathon previously underwent clinical examination and echocardiography at least
      10 days before the Berlin Marathon at rest. Standard transthoracic
      echocardiography and 2D strain and strain rate analysis were performed. The 2D
      Strain and strain rate values were compared to previous published data of healthy
      untrained individuals. RESULTS: The average global longitudinal peak systolic
      strain of the left ventricle was -23 +/- 2% with peak systolic strain rate -1.39
      +/- 0.21/s, early diastolic strain rate 2.0 +/- 0.40/s and late diastolic strain
      rate 1.21 +/- 0.31/s. These values are significantly higher compared to the
      previous published values of normal age-adjusted individuals. In addition, no age
      related decline of longitudinal contractility in well-trained athletes was
      observed. CONCLUSIONS: There is increased overall longitudinal myocardial
      contractility at rest in experienced endurance athletes compared to the published
      normal values in the literature indicating a preserved and even supra-normal
      contractility in the athletes. There is no age dependent decline of the
      longitudinal 2D Strain values. This underlines the beneficial effects of regular
      physical exercise even in advanced age.

PMID- 24571728
TI  - Career choice and future design of dental students in China and Japan.
AB  - The purpose of this study was to compare career choice and future plans of dental
      students in China and Japan. Information was derived from a self-answered
      questionnaire. Significant differences were detected for eight items between the
      two countries. Regarding motivation towards career choice, 41% of Japanese
      students indicated positive motives related to helping others, achieving self
      worth and health-care related interests, whereas Chinese students indicated that
      their choice was mainly for financial and prestige reasons, and for 32% of them,
      dentistry was a passive choice. More Chinese dental students (74%) wanted further
      education compared with Japanese students (22%). The majority of Japanese
      students (56.9%) planned to work as general dentists. Conversely, Chinese
      students were more likely to specialise (50%). More than 50% of Japanese students
      wanted to work in dental offices, but the majority of Chinese students (65%)
      preferred university hospital. We found it is strange that nearly one-fourth of
      the Chinese students did not want to be a clinical dentist mainly because of the
      poor health-care environment. This study provides a description of the
      perspectives of Japanese and Chinese dental students and enables a better
      understanding of career choices and future course design issues. 

PMID- 24571729
TI  - Quality of life is associated with physical activity and fitness in cystic
      fibrosis.
AB  - BACKGROUND: Health-related and disease-specific quality of life (HRQoL) has been
      increasingly valued as relevant clinical parameter in cystic fibrosis (CF)
      clinical care and clinical trials. HRQoL measures should assess - among other
      domains - daily functioning from a patient's perspective. However, validation
      studies for the most frequently used HRQoL questionnaire in CF, the Cystic
      Fibrosis Questionnaire (CFQ), have not included measures of physical activity or
      fitness. The objective of this study was, therefore, to determine the cross
      sectional and longitudinal relationships between HRQoL, physical activity and
      fitness in patients with CF. METHODS: Baseline (n = 76) and 6-month follow-up
      data (n = 70) from patients with CF (age >=12 years, FEV1 >=35%) were analysed.
      Patients participated in two multi-centre exercise intervention studies with
      identical assessment methodology. Outcome variables included HRQoL (German
      revised multi-dimensional disease-specific CFQ (CFQ-R)), body composition,
      pulmonary function, physical activity, short-term muscle power, and aerobic
      fitness by peak oxygen uptake and aerobic power. RESULTS: Peak oxygen uptake was
      positively related to 7 of 13 HRQoL scales cross-sectionally (r = 0.30-0.46).
      Muscle power (r = 0.25-0.32) and peak aerobic power (r = 0.24-0.35) were
      positively related to 4 scales each, and reported physical activity to 1 scale (r
      = 0.29). Changes in HRQoL-scores were directly and significantly related to
      changes in reported activity (r = 0.35-0.39), peak aerobic power (r = 0.31-0.34),
      and peak oxygen uptake (r = 0.26-0.37) in 3 scales each. Established associates
      of HRQoL such as FEV1 or body mass index correlated positively with fewer scales
      (all 0.24 < r < 0.55). CONCLUSIONS: HRQoL was associated with physical fitness,
      especially aerobic fitness, and to a lesser extent with reported physical
      activity. These findings underline the importance of physical fitness for HRQoL
      in CF and provide an additional rationale for exercise testing in this
      population. TRIAL REGISTRATION: ClinicalTrials.gov, NCT00231686.

PMID- 24571730
TI  - RbohB, a Phaseolus vulgaris NADPH oxidase gene, enhances symbiosome number,
      bacteroid size, and nitrogen fixation in nodules and impairs mycorrhizal
      colonization.
AB  - The reactive oxygen species (ROS) generated by respiratory burst oxidative
      homologs (Rbohs) are involved in numerous plant cell signaling processes, and
      have critical roles in the symbiosis between legumes and nitrogen-fixing
      bacteria. Previously, down-regulation of RbohB in Phaseolus vulgaris was shown to
      suppress ROS production and abolish Rhizobium infection thread (IT) progression,
      but also to enhance arbuscular mycorrhizal fungal (AMF) colonization. Thus, Rbohs
      function both as positive and negative regulators. Here, we assessed the effect
      of enhancing ROS concentrations, by overexpressing PvRbohB, on the P. vulgaris-
      rhizobia and P. vulgaris--AMF symbioses. We estimated superoxide concentrations
      in hairy roots overexpressing PvRbohB, determined the status of early and late
      events of both Rhizobium and AMF interactions in symbiont-inoculated roots, and
      analyzed the nodule ultrastructure of transgenic plants overexpressing PvRbohB.
      Overexpression of PvRbohB significantly enhanced ROS production, the formation of
      ITs, nodule biomass, and nitrogen-fixing activity, and increased the density of
      symbiosomes in nodules, and the density and size of bacteroides in symbiosomes.
      Furthermore, PvCAT, early nodulin, PvSS1, and PvGOGAT transcript abundances were
      elevated in these nodules. By contrast, mycorrhizal colonization was reduced in
      roots that overexpressed RbohB. Overexpression of PvRbohB augmented nodule
      efficiency by enhancing nitrogen fixation and delaying nodule senescence, but
      impaired AMF colonization.

PMID- 24571731
TI  - Structural disruption of phospholipid bilayers over a range of length scales by n
      butanol.
AB  - We report on the exposure of planar multicomponent lipid bilayers supported on
      mica to n-butanol. The bilayer contains 49 mol % 1,2-dioleoyl-sn
      phosphatidylcholine (DOPC), 10 mol % cholesterol, 40 mol % sphingomyelin, and 1
      mol % sulforhodamine-tagged 1,2-dioleoyl-sn-phosphatidylethanolamine (SR-DOPE).
      Phase separation of the cholesterol domains is seen within the bilayer structure,
      and exposure of this supported bilayer to controlled amounts of n-butanol in the
      aqueous overlayer produces morphological changes over a range of length scales.
      We report steady state fluorescence imaging, fluorescence lifetime imaging, and
      fluorescence anisotropy decay imaging for these bilayers. These data are
      consistent with literature reports on the interactions of lipid bilayers with n
      butanol and provide molecular-scale insight relative to bilayer organization that
      has not been available to date. The exposure of these bilayers to n-butanol leads
      to more extensive disruption of the bilayer than is seen for their exposure to
      ethanol. 

PMID- 24571732
TI  - The first report on flavonoid isolation from Annona crassiflora Mart.
AB  - Annona crassiflora, a native tree from Brazilian Cerrado, is reported to possess
      several ethnomedical uses. Here, we report the isolation and unambiguous
      characterisation of the flavonoids quercetin-3-O-beta-D-glucopyranosil(1 -> 6)-O
      alpha-L-arabinoside (1), known as peltatoside, kaempferol-3-O-beta-D
      galactopyranoside (2), quercetin-3-O-beta-D-galactopyranoside (3), quercetin-3-O
      beta-L-arabinopiranoside (4) and the ( - )-epicatechin (5) from the
      hydroalcoholic portion of the leaf ethanolic extract. Their structures were
      elucidated by using 1D and 2D NMR, ESI-MS, UV/Vis spectroscopy, optical rotation
      analysis and literature data comparison. The leaf ethanolic extract and its
      isolated compounds were evaluated by using antimicrobial, antioxidant and
      larvicidal assays, expressing antimicrobial and antioxidant activities. This is
      the first report on flavonoid isolation from A. crassiflora. 

PMID- 24571734
TI  - Rethinking band bending at the P3HT-TiO(2) interface.
AB  - The advancement of solar cell technology necessitates a detailed understanding of
      material heterojunctions and their interfacial properties. In hybrid bulk
      heterojunction solar cells (HBHJs), light-absorbing conjugated polymers are often
      interfaced with films of nanostructured TiO2 as a cheaper alternative to
      conventional inorganic solar cells. The mechanism of photovoltaic action requires
      photoelectrons in the polymer to transfer into the TiO2, and therefore, polymers
      are designed with lowest unoccupied molecular orbital (LUMO) levels higher in
      energy than the conduction band of TiO2 for thermodynamically favorable electron
      transfer. Currently, the energy level values used to guide solar cell design are
      referenced from the separated materials, neglecting the fact that upon
      heterojunction formation material energetics are altered. With
      spectroelectrochemistry, we discovered that spontaneous charge transfer occurs
      upon heterojunction formation between poly(3-hexylthiophene) (P3HT) and
      nanocrystalline TiO2. It was determined that deep trap states (0.5 eV below the
      conduction band of TiO2) accept electrons from P3HT and form hole polarons in the
      polymer. This equilibrium charge separation alters energetics through the
      formation of interfacial dipoles and results in band bending that inhibits
      desired photoelectron injection into TiO2, limiting HBHJ solar cell performance.
      X-ray photoelectron spectroscopic studies quantified the resultant vacuum level
      offset to be 0.8 eV. Further spectroelectrochemical studies indicate that 0.1 eV
      of this offset occurs in TiO2, whereas the balance occurs in P3HT. New guidelines
      for improved photocurrent are proposed by tuning the energetics of the
      heterojunction to reverse the direction of the interfacial dipole, enhancing
      photoelectron injection. 

PMID- 24571733
TI  - Salvage cytoreductive surgery for patients with recurrent endometrial cancer: a
      retrospective study.
AB  - BACKGROUND: Salvage cytoreductive surgery (SCR) has been shown to improve the
      survival of cancer patients. This study aimed to determine the survival benefits
      of SCR for recurrent endometrial cancer in Chinese population. METHODS: Between
      January 1995 and May 2012, 75 Chinese patients with recurrent endometrial cancer
      undergoing SCR were retrospectively analyzed. RESULTS: 43 patients (57.3%) had R0
      (no visible disease), 15 patients (20.0%) had R1 (residual disease <=1 cm), and
      17 (22.7%) had R2 (residual disease >1 cm) Resection. 35 patients (46.7%) had
      single, and 40 (53.3%) had multiple sites of recurrence. The median survival time
      was 18 months, and 5-year overall survival (OS) rate were 42.0%. Multivariate
      analysis showed that residual disease <=1 cm and high histology grade were
      significantly associated with a better OS. The size of the largest recurrent
      tumors (<=6 cm), solitary recurrent tumor, and age at recurrence (<=56 years old)
      were associated with optimal SCR. CONCLUSION: Optimal SCR and high histology
      grade are associated with prolonged overall survival for patients with recurrent
      endometrial cancer. Patients with young age, tumor size < 6 cm, and solitary
      recurrent tumor are more likely to benefit from optimal cytoreductive surgery.

PMID- 24571735
TI  - Diurnal variation of von Willebrand factor in plasma: the Bispebjerg study of
      diurnal variations.
AB  - BACKGROUND: Quantitation of von Willebrand factor (VWF) in plasma is a central
      element in assessing von Willebrand disease (VWD). VWF activity is known to vary,
      which has partly been ascribed to biological and preanalytical variation.
      However, a possible diurnal expression of VWF has not been thoroughly tested.
      OBJECTIVES: We examined whether VWF antigen and VWF activity in plasma display a
      diurnal profile in healthy young males, and whether such variation is related to
      changes in release or elimination. METHODS: Plasma from 20 healthy young males
      was collected at 9 time-points over 24 h (15 h of light and 9 h of darkness); the
      plasma concentration of melatonin was used as an internal control to confirm the
      normal 24-h rhythms of the individual participants. RESULTS: The data, analyzed
      by rhythmometric statistics, revealed a significant variation (P = 0.02) and
      total amplitude of 22.6% in VWF antigen concentrations over the 24-h period. A
      pronounced variation in VWF activity was also observed, although not significant
      according to the 24-h statistical model. To examine whether the diurnal pattern
      was related to changes in elimination or secretion, the ratio between (i)
      coagulation factor VIII and VWF and (ii) VWF propeptide and VWF was determined.
      Taken together, the data suggest changes in release and not in clearance.
      CONCLUSIONS: Diurnal variation in von Willebrand antigen and activity in plasma
      represents an important aspect of the biological variation. Standardized time-of
      day plasma sampling for quantitation of VWF in VWD patients seems warranted.

PMID- 24571736
TI  - Does social defeat mediate the association between childhood trauma and
      psychosis? Evidence from the NEMESIS-2 Study.
AB  - OBJECTIVE: Based on theoretical considerations and animal studies, mediation of
      'social defeat' (SD) in the association between childhood trauma (CT) and
      psychosis was investigated. METHOD: Trained interviewers administered a
      structured interview assessing CT, psychotic experiences and other
      psychopathology in 6646 participants in the second Netherlands Mental Health
      Survey and Incidence Study (NEMESIS-2). RESULTS: Childhood trauma was associated
      with psychotic experiences making up the extended psychosis phenotype (EPP), as
      well as with a diagnosis of psychotic disorder (PD). Similarly, CT was associated
      with a priori selected items indexing SD (discouraged, hopeless, worthless, loss
      of self-confidence, low self-esteem, better off dead, suicidal thoughts) and with
      a measure of affective dysregulation (AD), which in turn were also associated
      with psychosis. While SD and AD individually acted as mediators in the
      association between CT and EPP, only SD acted as a mediator in the association
      between CT and PD. Cannabis use did not mediate the association between CT and
      EPP or PD. CONCLUSION: The present results suggest a developmental model
      implicating SD as an important mediator in the link between childhood adverse
      experiences and later development of psychotic experiences. The combined
      mediation by SD and AD is compatible with an 'affective pathway' to early
      psychosis.

PMID- 24571737
TI  - Targeting kallikrein-related peptidases in prostate cancer.
AB  - INTRODUCTION: Novel therapeutic compounds are needed for prostate cancer (CaP),
      given the limitations of already used drugs and the disease's mortality, often
      attributed to castrate resistance. Tissue kallikrein and kallikrein-related
      peptidases (KLKs) form a family of serine proteases aberrantly expressed and
      broadly implicated in human malignancies. In CaP, KLKs participate in the
      promotion of cell proliferation, extracellular matrix degradation, tumour cell
      invasion and metastasis. AREAS COVERED: This review discusses the different ways
      of inhibiting, modulating and exploiting KLK activity and/or expression as
      emerging CaP therapeutics. KLKs are targeted by diverse naturally occurring
      substances, including proteinaceous inhibitors, low-molecular-weight peptides and
      Zn(2+). Synthetic KLK inhibitors include protein/peptide-based inhibitors and
      small molecules. A re-engineered serpin-based KLK inhibitor is under evaluation
      in first-in-human trials as a CaP therapeutic, whereas additional potent and
      selective KLK inhibitors with relevance to CaP have been synthesized. KLK3
      activated pro-drugs have entered Phase I and Phase II clinical trials as
      therapeutics for prostate tumours. The KLK3-based PROSTVAC(r) vaccine is
      evaluated in Phase III clinical trials. Targeting KLK expression via RNA
      interference methods could represent another promising therapeutic approach for
      CaP. EXPERT OPINION: Apart from their immense biomarker potential, KLKs also hold
      promise as the basis of novel CaP therapeutics.

PMID- 24571738
TI  - Predictors of financial capacity performance in older adults using the Financial
      Competence Assessment Inventory.
AB  - BACKGROUND: Declines in financial capacity in later life may arise from both
      neurocognitive and/or psychiatric disorders. The influence of socio-demographic,
      cognitive, health, and psychiatric variables on financial capacity performance
      was explored. METHODS: Seventy-six healthy community-dwelling adults and 25 older
      patients referred for assessment of financial capacity were assessed on pertinent
      cognitive, psychiatric, and financial capacity measures, including Addenbrooke's
      Cognitive Examination - Revised (ACE-R), Informant Questionnaire on Cognitive
      Decline in the Elderly (IQCODE), Geriatric Depression Scale (GDS), Geriatric
      Anxiety Inventory (GAI), selected Neuropsychiatric Inventory (NPI) items,
      Financial Competence Assessment Inventory (FCAI), and Social Vulnerability Scale
      (SVS). RESULTS: The internal consistency of the debt management subscale of the
      FCAI was relatively poor in our sample. Financial capacity performance differed
      between controls and patients. In our sample, performance on the FCAI was
      predicted by Mini-Mental State Examination, IQCODE, and GAI, but not by ACE-R,
      GDS, NPI items, or SVS (adjusted R(2) = 0.7059). CONCLUSIONS: Anxiety but not
      depression predicted financial capacity performance, possibly reflecting
      relatively low variance of depressive symptoms in this sample. Current cognitive
      decline as measured by the informant-rated IQCODE was more highly correlated to
      financial capacity than either educational attainment or ACE-R scores. Lack of
      significance of ACE-R data may reflect the instrument's decreased sensitivity to
      domains relevant to financial capacity, compared with more detailed
      neuropsychological assessment tools. The FCAI displayed fairly robust
      psychometric properties apart from the debt management subscale.

PMID- 24571739
TI  - Combining phospholipases and a liquid lipase for one-step biodiesel production
      using crude oils.
AB  - BACKGROUND: Enzymatic biodiesel is becoming an increasingly popular topic in
      bioenergy literature because of its potential to overcome the problems posed by
      chemical processes. However, the high cost of the enzymatic process still remains
      the main drawback for its industrial application, mostly because of the high
      price of refined oils. Unfortunately, low cost substrates, such as crude soybean
      oil, often release a product that hardly accomplishes the final required
      biodiesel specifications and need an additional pretreatment for gums removal. In
      order to reduce costs and to make the enzymatic process more efficient, we
      developed an innovative system for enzymatic biodiesel production involving a
      combination of a lipase and two phospholipases. This allows performing the
      enzymatic degumming and transesterification in a single step, using crude soybean
      oil as feedstock, and converting part of the phospholipids into biodiesel. Since
      the two processes have never been studied together, an accurate analysis of the
      different reaction components and conditions was carried out. RESULTS: Crude
      soybean oil, used as low cost feedstock, is characterized by a high content of
      phospholipids (900 ppm of phosphorus). However, after the combined activity of
      different phospholipases and liquid lipase Callera Trans L, a complete
      transformation into fatty acid methyl esters (FAMEs >95%) and a good reduction of
      phosphorus (P <5 ppm) was achieved. The combination of enzymes allowed avoidance
      of the acid treatment required for gums removal, the consequent caustic
      neutralization, and the high temperature commonly used in degumming systems,
      making the overall process more eco-friendly and with higher yield. Once the
      conditions were established, the process was also tested with different vegetable
      oils with variable phosphorus contents. CONCLUSIONS: Use of liquid lipase Callera
      Trans L in biodiesel production can provide numerous and sustainable benefits.
      Besides reducing the costs derived from enzyme immobilization, the lipase can be
      used in combination with other enzymes such as phospholipases for gums removal,
      thus allowing the use of much cheaper, non-refined oils. The possibility to
      perform degumming and transesterification in a single tank involves a great
      efficiency increase in the new era of enzymatic biodiesel production at
      industrial scale.

PMID- 24571740
TI  - Substantial early loss of induced pluripotent stem cells following
      transplantation in myocardial infarction.
AB  - The limited success of cardiac stem cell therapy has lately generated discussion
      regarding its effectiveness. We hypothesized that immediate cell loss after
      intramyocardial injection significantly obscures the regenerative potential of
      stem cell therapy. Therefore, our aim was to assess the distribution and quantity
      of induced pluripotent stem cells after intramyocardial delivery using in vivo
      bioluminescence analysis. In this context, we wanted to investigate if the
      injection of different cell concentrations would exert influence on cardiac cell
      retention. Murine-induced pluripotent stem cells were transfected for luciferase
      reporter gene expression and transplanted into infarcted myocardium in mice after
      left anterior descending coronary artery ligation. Cells were delivered
      constantly in aqueous media (15 MUL) in different cell concentrations (group A, n
      = 10, 5.0 * 10(5) cells; group B, n = 10, 1.0 * 10(6) cells). Grafts were
      detected using bioluminescence imaging. Organ explants were imaged 10 min after
      injection to quantify early cardiac retention and cell biodistribution.
      Bioluminescence imaging showed a massive early displacement from the injection
      site to the pulmonary circulation, leading to lung accumulation. Mean cell counts
      of explanted organs in group A were 7.51 * 10(4) +/- 4.09 * 10(3) (heart), 6.44 *
      10(4) +/- 2.48 * 10(3) (left lung), and 8.06 * 10(5) +/- 3.61 * 10(3) (right
      lung). Respective cell counts in group B explants were 1.69 * 10(5) +/- 7.69 *
      10(4) (heart), 2.11 * 10(5) +/- 4.58 * 10(3) (left lung), and 3.25 * 10(5) +/-
      9.35 * 10(3) (right lung). Applying bioluminescence imaging, we could unveil and
      quantify massive early cardiac stem cell loss and pulmonary cell accumulation
      following intramyocardial injection. Increased injection concentrations led to
      much higher intracardiac cell counts; however, pulmonary biodistribution of
      transplanted cells still persisted. Therefore, we recommend applying tissue
      engineering techniques for cardiac stem cell transplantations in order to improve
      cardiac retention and limit biodistribution.

PMID- 24571741
TI  - Monitoring water sources for environmental reservoirs of toxigenic Vibrio
      cholerae O1, Haiti.
AB  - An epidemic of cholera infections was documented in Haiti for the first time in
      more than 100 years during October 2010. Cases have continued to occur, raising
      the question of whether the microorganism has established environmental
      reservoirs in Haiti. We monitored 14 environmental sites near the towns of
      Gressier and Leogane during April 2012-March 2013. Toxigenic Vibrio cholerae O1
      El Tor biotype strains were isolated from 3 (1.7%) of 179 water samples;
      nontoxigenic O1 V. cholerae was isolated from an additional 3 samples. All
      samples containing V. cholerae O1 also contained non-O1 V. cholerae. V. cholerae
      O1 was isolated only when water temperatures were >=31 degrees C. Our data
      substantiate the presence of toxigenic V. cholerae O1 in the aquatic environment
      in Haiti. These isolations may reflect establishment of long-term environmental
      reservoirs in Haiti, which may complicate eradication of cholera from this
      coastal country. 

PMID- 24571743
TI  - Fetuin-A-containing calciprotein particle levels can be reduced by dialysis,
      sodium thiosulphate and plasma exchange. Potential therapeutic implications for
      calciphylaxis?
AB  - Calciprotein particles (CPP) are a novel marker of mineral stress. High levels of
      CPP are found in patients with calciphylaxis, a condition associated with marked
      vascular calcification and a poor prognosis. We report substantial reductions in
      CPP levels in a dialysis patient having combined haemodialysis (HD) and plasma
      exchange (PEx) prior to an ABO-incompatible kidney transplant. We also report the
      effects of the same treatments combined with sodium thiosulphate (STS) in a
      patient newly diagnosed with calciphylaxis. Combining HD with intra-dialytic STS
      and PEx we achieved a significant reduction in CCP with the least rebound between
      treatment sessions. After 6 weeks of treatment, the CPP reduction was paralleled
      by clinical improvement. Measurement of CPP may be an attractive marker for
      monitoring the effectiveness of calciphylaxis therapy. 

PMID- 24571742
TI  - Physical and psychological long-term outcome after traumatic brain injury in
      children and adult patients.
AB  - BACKGROUND: Several studies have indicated that younger age is associated with
      worse recovery after pediatric traumatic brain injury (TBI) compared to elder
      children. In order to verify this association between long-term outcome after
      moderate to severe TBI and patient's age, direct comparison between different
      pediatric age groups as well as an adult population was performed. METHODS: This
      investigation represents a retrospective cohort study at a level I trauma center
      including patients with moderate to severe, isolated TBI with a minimum follow-up
      of 10 years. According to their age at time of injury, patients were divided in
      pre-school (0-7 years), school (8-17 years) and adult (18-65 years) patients.
      Physical examination and standardized questionnaire on physical and psychological
      aspects (Glasgow Outcome Scale, Barthel Index, Impact of Event Scale, Hospital
      Anxiety and Depression Scale, short form 12) were performed. RESULTS: 135
      traumatized patients were included. Physical and psychological long-term outcome
      was associated with injury severity but not with patients' age at time of injury.
      Outcome recovery measured by Glasgow Outcome Scale was demonstrated with best
      results for pre-school aged children (p = 0.009). According to the Hospital
      Anxiety and Depression Scale an increased incidence of anxiety (p = 0.010) and
      depression (p = 0.026) was evaluated in older patients. CONCLUSION: Long-term
      outcome perceptions after moderate to severe TBI presented in this study question
      current views of deteriorated recovery for the immature brain. The sustained TBI
      impact seemed not to reduce the child's ability to overcome the suffered
      impairment measured by questionnaire based psychological, physical and health
      related outcome scores. These results distinguish the relevance of rehabilitation
      and family support in the long term.

PMID- 24571745
TI  - Right shoulder pain in peritoneal dialysis.

PMID- 24571744
TI  - Combination of caspofungin and low-dose trimethoprim/sulfamethoxazole for the
      treatment of severe Pneumocystis jirovecii pneumonia in renal transplant
      recipients.
AB  - Pneumocystis jirovecii pneumonia (PJP) is a severe and life-threatening
      complication in immunocompromised patients. Trimethoprim/sulfamethoxazole (TMP
      SMZ) is well known for its effectiveness as prophylaxis of PJP. However, the use
      of TMP-SMZ is associated with various adverse effects that may not be tolerated
      by critically ill patients. Caspofungin is recommended for invasive fungal
      infections, but the treatment of PJP after solid organ transplantation (SOT) is
      an off-label use of this drug. In this study, three cases of severe PJP in renal
      transplant recipients treated with a combination of caspofungin and low-dose TMP
      SMZ were presented. Initial findings indicated that the combined treatment may be
      beneficial for the treatment of PJP and decrease the incidence of TMP-SMZ-related
      adverse effects. 

PMID- 24571746
TI  - Transition of overlooked sterile pyuria.

PMID- 24571747
TI  - Arachnoid cyst in autosomal dominant polycystic kidney disease patient.

PMID- 24571748
TI  - Renal macrophages in autosomal recessive polycystic kidney disease.

PMID- 24571749
TI  - Improved plant resistance to drought is promoted by the root-associated
      microbiome as a water stress-dependent trait.
AB  - Although drought is an increasing problem in agriculture, the contribution of the
      root-associated bacterial microbiome to plant adaptation to water stress is
      poorly studied. We investigated if the culturable bacterial microbiome associated
      with five grapevine rootstocks and the grapevine cultivar Barbera may enhance
      plant growth under drought stress. Eight isolates, over 510 strains, were tested
      in vivo for their capacity to support grapevine growth under water stress. The
      selected strains exhibited a vast array of plant growth promoting (PGP) traits,
      and confocal microscopy observation of gfp-labelled Acinetobacter and Pseudomonas
      isolates showed their ability to adhere and colonize both the Arabidopsis and
      grapevine rhizoplane. Tests on pepper plants fertilized with the selected
      strains, under both optimal irrigation and drought conditions, showed that PGP
      activity was a stress-dependent and not a per se feature of the strains. The
      isolates were capable of increasing shoot and leaf biomass, shoot length, and
      photosynthetic activity of drought-challenged grapevines, with an enhanced effect
      in drought-sensitive rootstock. Three isolates were further assayed for PGP
      capacity under outdoor conditions, exhibiting the ability to increase grapevine
      root biomass. Overall, the results indicate that PGP bacteria contribute to
      improve plant adaptation to drought through a water stress-induced promotion
      ability. 

PMID- 24571750
TI  - Enterovirus vaccines for an emerging cause of brain-stem encephalitis.

PMID- 24571751
TI  - Pancreatic safety of incretin-based drugs--FDA and EMA assessment.

PMID- 24571752
TI  - DNA sequencing versus standard prenatal aneuploidy screening.
AB  - BACKGROUND: In high-risk pregnant women, noninvasive prenatal testing with the
      use of massively parallel sequencing of maternal plasma cell-free DNA (cfDNA
      testing) accurately detects fetal autosomal aneuploidy. Its performance in low
      risk women is unclear. METHODS: At 21 centers in the United States, we collected
      blood samples from women with singleton pregnancies who were undergoing standard
      aneuploidy screening (serum biochemical assays with or without nuchal
      translucency measurement). We performed massively parallel sequencing in a
      blinded fashion to determine the chromosome dosage for each sample. The primary
      end point was a comparison of the false positive rates of detection of fetal
      trisomies 21 and 18 with the use of standard screening and cfDNA testing. Birth
      outcomes or karyotypes were the reference standard. RESULTS: The primary series
      included 1914 women (mean age, 29.6 years) with an eligible sample, a singleton
      fetus without aneuploidy, results from cfDNA testing, and a risk classification
      based on standard screening. For trisomies 21 and 18, the false positive rates
      with cfDNA testing were significantly lower than those with standard screening
      (0.3% vs. 3.6% for trisomy 21, P<0.001; and 0.2% vs. 0.6% for trisomy 18,
      P=0.03). The use of cfDNA testing detected all cases of aneuploidy (5 for trisomy
      21, 2 for trisomy 18, and 1 for trisomy 13; negative predictive value, 100% [95%
      confidence interval, 99.8 to 100]). The positive predictive values for cfDNA
      testing versus standard screening were 45.5% versus 4.2% for trisomy 21 and 40.0%
      versus 8.3% for trisomy 18. CONCLUSIONS: In a general obstetrical population,
      prenatal testing with the use of cfDNA had significantly lower false positive
      rates and higher positive predictive values for detection of trisomies 21 and 18
      than standard screening. (Funded by Illumina; ClinicalTrials.gov number,
      NCT01663350.).

PMID- 24571753
TI  - Beyond malaria--causes of fever in outpatient Tanzanian children.
AB  - BACKGROUND: As the incidence of malaria diminishes, a better understanding of
      nonmalarial fever is important for effective management of illness in children.
      In this study, we explored the spectrum of causes of fever in African children.
      METHODS: We recruited children younger than 10 years of age with a temperature of
      38 degrees C or higher at two outpatient clinics--one rural and one urban--in
      Tanzania. Medical histories were obtained and clinical examinations conducted by
      means of systematic procedures. Blood and nasopharyngeal specimens were collected
      to perform rapid diagnostic tests, serologic tests, culture, and molecular tests
      for potential pathogens causing acute fever. Final diagnoses were determined with
      the use of algorithms and a set of prespecified criteria. RESULTS: Analyses of
      data derived from clinical presentation and from 25,743 laboratory investigations
      yielded 1232 diagnoses. Of 1005 children (22.6% of whom had multiple diagnoses),
      62.2% had an acute respiratory infection; 5.0% of these infections were
      radiologically confirmed pneumonia. A systemic bacterial, viral, or parasitic
      infection other than malaria or typhoid fever was found in 13.3% of children,
      nasopharyngeal viral infection (without respiratory symptoms or signs) in 11.9%,
      malaria in 10.5%, gastroenteritis in 10.3%, urinary tract infection in 5.9%,
      typhoid fever in 3.7%, skin or mucosal infection in 1.5%, and meningitis in 0.2%.
      The cause of fever was undetermined in 3.2% of the children. A total of 70.5% of
      the children had viral disease, 22.0% had bacterial disease, and 10.9% had
      parasitic disease. CONCLUSIONS: These results provide a description of the
      numerous causes of fever in African children in two representative settings.
      Evidence of a viral process was found more commonly than evidence of a bacterial
      or parasitic process. (Funded by the Swiss National Science Foundation and
      others.).

PMID- 24571754
TI  - Efficacy, safety, and immunogenicity of an enterovirus 71 vaccine in China.
AB  - BACKGROUND: Enterovirus 71 (EV71) is one of the major causative agents of
      outbreaks of hand, foot, and mouth disease or herpangina worldwide. This phase 3
      trial was designed to evaluate the efficacy, safety, and immunogenicity of an
      EV71 vaccine. METHODS: We conducted a randomized, double-blind, placebo
      controlled, multicenter trial in which 10,007 healthy infants and young children
      (6 to 35 months of age) were randomly assigned in a 1:1 ratio to receive two
      intramuscular doses of either EV71 vaccine or placebo, 28 days apart. The
      surveillance period was 12 months. The primary end point was the occurrence of
      EV71-associated hand, foot, and mouth disease or herpangina. RESULTS: During the
      12-month surveillance period, EV71-associated disease was identified in 0.3% of
      vaccine recipients (13 of 5041 children) and 2.1% of placebo recipients (106 of
      5028 children) in the intention-to-treat cohort. The vaccine efficacy against
      EV71-associated hand, foot, and mouth disease or herpangina was 94.8% (95%
      confidence interval [CI], 87.2 to 97.9; P<0.001) in this cohort. Vaccine
      efficacies against EV71-associated hospitalization (0 cases vs. 24 cases) and
      hand, foot, and mouth disease with neurologic complications (0 cases vs. 8 cases)
      were both 100% (95% CI, 83.7 to 100 and 42.6 to 100, respectively). Serious
      adverse events occurred in 111 of 5044 children in the vaccine group (2.2%) and
      131 of 5033 children in the placebo group (2.6%). In the immunogenicity subgroup
      (1291 children), an anti-EV71 immune response was elicited by the two-dose
      vaccine series in 98.8% of participants at day 56. An anti-EV71 neutralizing
      antibody titer of 1:16 was associated with protection against EV71-associated
      hand, foot, and mouth disease or herpangina. CONCLUSIONS: The EV71 vaccine
      provided protection against EV71-associated hand, foot, and mouth disease or
      herpangina in infants and young children. (Funded by Sinovac Biotech;
      ClinicalTrials.gov number, NCT01507857.).

PMID- 24571756
TI  - Clinical practice. Attention deficit-hyperactivity disorder in children and
      adolescents.

PMID- 24571755
TI  - An inactivated enterovirus 71 vaccine in healthy children.
AB  - BACKGROUND: Enterovirus 71 (EV71) is a major cause of hand, foot, and mouth
      disease in children and may be fatal. A vaccine against EV71 is needed. METHODS:
      We conducted a randomized, double-blind, placebo-controlled phase 3 trial
      involving healthy children 6 to 71 months of age in Guangxi Zhuang Autonomous
      Region, China. Two doses of an inactivated EV71 vaccine or placebo were
      administered intramuscularly, with a 4-week interval between doses, and children
      were monitored for up to 11 months. The primary end point was protection against
      hand, foot, and mouth disease caused by EV71. RESULTS: A total of 12,000 children
      were randomly assigned to receive vaccine or placebo. Serum neutralizing
      antibodies were assessed in 549 children who received the vaccine. The
      seroconversion rate was 100% 4 weeks after the two vaccinations, with a geometric
      mean titer of 170.6. Over the course of two epidemic seasons, the vaccine
      efficacy was 97.4% (95% confidence interval [CI], 92.9 to 99.0) according to the
      intention-to-treat analysis and 97.3% (95% CI, 92.6 to 99.0) according to the per
      protocol analysis. Adverse events, such as fever (which occurred in 41.6% of the
      participants who received vaccine vs. 35.2% of those who received placebo), were
      significantly more common in the week after vaccination among children who
      received the vaccine than among those who received placebo. CONCLUSIONS: The
      inactivated EV71 vaccine elicited EV71-specific immune responses and protection
      against EV71-associated hand, foot, and mouth disease. (Funded by the National
      Basic Research Program and others; ClinicalTrials.gov number, NCT01569581.).

PMID- 24571757
TI  - Bleeding and coagulopathies in critical care.

PMID- 24571758
TI  - Images in clinical medicine. Adamantinomatous craniopharyngioma containing teeth.

PMID- 24571759
TI  - Case records of the Massachusetts General Hospital. Case 7-2014. A 27-year-old
      man with diarrhea, fatigue, and eosinophilia.

PMID- 24571760
TI  - Screening for trisomies in circulating DNA.

PMID- 24571761
TI  - New diagnostics for common childhood infections.

PMID- 24571762
TI  - Vitamin D-binding protein and vitamin D in blacks and whites.

PMID- 24571764
TI  - Vitamin D-binding protein and vitamin D in blacks and whites.

PMID- 24571763
TI  - Vitamin D-binding protein and vitamin D in blacks and whites.

PMID- 24571765
TI  - Vitamin D-binding protein and vitamin D in blacks and whites.

PMID- 24571766
TI  - Vitamin D-binding protein and vitamin D in blacks and whites.

PMID- 24571767
TI  - Nut consumption and mortality.

PMID- 24571768
TI  - Nut consumption and mortality.

PMID- 24571769
TI  - Nut consumption and mortality.

PMID- 24571770
TI  - Laryngeal mask airway in medical emergencies.

PMID- 24571771
TI  - Laryngeal mask airway in medical emergencies.

PMID- 24571772
TI  - Laryngeal mask airway in medical emergencies.

PMID- 24571773
TI  - Dead man walking.

PMID- 24571774
TI  - Dead man walking.

PMID- 24571775
TI  - Two cases of invasive vancomycin-resistant group B streptococcus infection.

PMID- 24571779
TI  - Images in clinical medicine. Vanishing lung syndrome.

PMID- 24571780
TI  - Pharmacologic therapy for diabetic retinopathy.
AB  - Diabetic retinopathy is one of the most serious complications of chronic diabetes
      mellitus and is the leading cause of blindness in working-age populations. Large,
      randomized studies have demonstrated the benefits of systemic and ocular therapy
      in the prevention and treatment of diabetic retinopathy. The process of
      angiogenesis plays a critical role in the development of diabetic complications.
      VEGF is part of the angiogenic process and gives rise to retinal
      neovascularizations, which are part of the proliferative diabetic retinopathy.
      Various types of anti-VEGF drugs for the treatment of diabetic macular edema are
      currently being tested in ongoing clinical trials. Recently published prospective
      studies addressing the impact of anti-VEGF drugs on diabetic macular edema and
      proliferative diabetic retinopathy showed the clinical effects of these drugs and
      uncovered possible adverse effects. Herein we present a review on therapy of
      diabetic retinopathy with a special focus on anti-VEGF therapy. 

PMID- 24571781
TI  - Elucidating substrate promiscuity in the human cytochrome 3A4.
AB  - The human cytochrome P450 enzymes (CYPs) are heme-protein monooxygenases, which
      catalyze oxidative reactions of a broad spectrum of substrates. Consequently,
      they play a critical role in the metabolism of xenobiotics, such as drugs and
      carcinogens, and the catabolism of endogenous lipophilic factors. Bioavailability
      and toxicity, both of which can be related to CYPs, continue to pose problems in
      the development of new drugs. The isoform which metabolizes over one-third of
      drugs, CYP 3A4, was investigated employing ensemble-docking experiments of a 195
      substrate library with induced fit and GOLD docking algorithms and a number of
      scoring functions. Enzyme conformations included three currently available CYP
      3A4 crystal structures. All docking experiments were performed in duplicates with
      and without inclusion of crystallographic waters. Resultant poses were assessed
      based on accuracy of site of metabolism prediction. Analyses of the docked
      solutions pertaining to ranking efficacy, ligand molecular properties,
      stabilizing residues in the ligand-enzyme complexes, and metabolic reactions are
      discussed. Our analyses suggest that certain residues make favorable interactions
      with the bound substrates. Employing multiple receptor conformations enhances the
      accuracy of catalytic prediction, while ligand size and flexibility impact
      docking performance. The presence of waters observed in crystal complexes does
      not necessarily lead to improved performance. 

PMID- 24571784
TI  - Divergent syntheses of 2-aminonicotinonitriles and pyrazolines by copper
      catalyzed cyclization of oxime ester.
AB  - Copper-catalyzed cyclization of an oxime ester toward divergent heterocycle
      synthesis is reported. Oxime ester serves as an enamine precursor to cyclize with
      malononitrile and aldehydes for access to 2-aminonicotinonitriles in a one-pot
      reaction, while cyclizing with N-sulfonylimines leads to synthesis of
      pyrazolines. 

PMID- 24571782
TI  - Flower development of Phalaenopsis orchid involves functionally divergent
      SEPALLATA-like genes.
AB  - The Phalaenopsis orchid produces complex flowers that are commercially valuable,
      which has promoted the study of its flower development. E-class MADS-box genes,
      SEPALLATA (SEP), combined with B-, C- and D-class MADS-box genes, are involved in
      various aspects of plant development, such as floral meristem determination,
      organ identity, fruit maturation, seed formation and plant architecture. Four SEP
      like genes were cloned from Phalaenopsis orchid, and the duplicated PeSEPs were
      grouped into PeSEP1/3 and PeSEP2/4. All PeSEPs were expressed in all floral
      organs. PeSEP2 expression was detectable in vegetative tissues. The study of
      protein-protein interactions suggested that PeSEPs may form higher order
      complexes with the B-, C-, D-class and AGAMOUS LIKE6-related MADS-box proteins to
      determine floral organ identity. The tepal became a leaf-like organ when PeSEP3
      was silenced by virus-induced silencing, with alterations in epidermis identity
      and contents of anthocyanin and chlorophyll. Silencing of PeSEP2 had minor
      effects on the floral phenotype. Silencing of the E-class genes PeSEP2 and PeSEP3
      resulted in the downregulation of B-class PeMADS2-6 genes, which indicates an
      association of PeSEP functions and B-class gene expression. These findings reveal
      the important roles of PeSEP in Phalaenopsis floral organ formation throughout
      the developmental process by the formation of various multiple protein complexes.

PMID- 24571785
TI  - Bias in discriminating very mild dementia for older adults with different levels
      of education in Hong Kong.
AB  - BACKGROUND: Education has a profound effect on older adults' cognitive
      performance. In Hong Kong, some dementia screening tasks were originally designed
      for developed population with, on average, higher education. METHODS: We compared
      the screening power of these tasks for Chinese older adults with different levels
      of education. Community-dwelling older adults who were healthy (N = 383) and with
      very mild dementia (N = 405) performed the following tasks: Mini-Mental State
      Examination, Alzheimer's Disease Assessment Scale-Cognitive subscales, Verbal
      Fluency, Abstract Thinking, and Visual/Digit Span. Logistic regression was used
      to examine the power of these tasks to predict Clinical Dementia Rating (CDR 0.5
      vs. 0). RESULTS: Logistic regression analysis showed that while the screening
      power of the total scores in all tasks was similar for high and low education
      groups, there were education biases in some items of these tasks. CONCLUSION: The
      differential screening power in high and low education groups was not identical
      across items in some tasks. Thus, in cognitive assessments, we should exercise
      great caution when using these potentially biased items for older adults with
      limited education.

PMID- 24571783
TI  - MRI and CT imaging for preoperative target volume delineation in breast
      conserving therapy.
AB  - BACKGROUND: Accurate tumor bed delineation after breast-conserving surgery is
      important. However, consistency among observers on standard postoperative
      radiotherapy planning CT is low and volumes can be large due to seroma formation.
      A preoperative delineation of the tumor might be more consistent. Therefore, the
      purpose of this study was to determine the consistency of preoperative target
      volume delineation on CT and MRI for breast-conserving radiotherapy. METHODS:
      Tumors were delineated on preoperative contrast-enhanced (CE) CT and newly
      developed 3D CE-MR images, by four breast radiation oncologists. Clinical target
      volumes (CTVs) were created by addition of a 1.5 cm margin around the tumor,
      excluding skin and chest wall. Consistency in target volume delineation was
      expressed by the interobserver variability. Therefore, the conformity index (CI),
      center of mass distance (dCOM) and volumes were calculated. Tumor characteristics
      on CT and MRI were scored by an experienced breast radiologist. RESULTS:
      Preoperative tumor delineation resulted in a high interobserver agreement with a
      high median CI for the CTV, for both CT (0.80) and MRI (0.84). The tumor was
      missed on CT in 2/14 patients (14%). Leaving these 2 patients out of the
      analysis, CI was higher on MRI compared to CT for the GTV (p<0.001) while not for
      the CTV (CT (0.82) versus MRI (0.84), p=0.123). The dCOM did not differ between
      CT and MRI. The median CTV was 48 cm3 (range 28-137 cm3) on CT and 59 cm3 (range
      30-153 cm3) on MRI (p<0.001). Tumor shapes and margins were rated as more
      irregular and spiculated on CE-MRI. CONCLUSIONS: This study showed that
      preoperative target volume delineation resulted in small target volumes with a
      high consistency among observers. MRI appeared to be necessary for tumor
      detection and the visualization of irregularities and spiculations. Regarding the
      tumor delineation itself, no clinically relevant differences in interobserver
      variability were observed. These results will be used to study the potential for
      future MRI-guided and neoadjuvant radiotherapy. TRIAL REGISTRATION: International
      Clinical Trials Registry Platform NTR3198.

PMID- 24571787
TI  - Transition paths of Met-enkephalin from Markov state modeling of a molecular
      dynamics trajectory.
AB  - Conformational states and their interconversion pathways of the zwitterionic form
      of the pentapeptide Met-enkephalin (MetEnk) are identified. An explicit solvent
      molecular dynamics (MD) trajectory is used to construct a Markov state model
      (MSM) based on dihedral space clustering of the trajectory, and transition path
      theory (TPT) is applied to identify pathways between open and closed conformers.
      In the MD trajectory, only four of the eight backbone dihedrals exhibit bistable
      behavior. Defining a conformer as the string XXXX with X = "+" or "-" denoting,
      respectively, positive or negative values of a given dihedral angle and obtaining
      the populations of these conformers shows that only four conformers are highly
      populated, implying a strong correlation among these dihedrals. Clustering in
      dihedral space to construct the MSM finds the same four bistable dihedral angles.
      These state populations are very similar to those found directly from the MD
      trajectory. TPT is used to obtain pathways, parametrized by committor values, in
      dihedral state space that are followed in transitioning from closed to open
      states. Pathway costs are estimated by introducing a kinetics-based procedure
      that orders pathways from least (shortest) to greater cost paths. The least
      costly pathways in dihedral space are found to only involve the same XXXX set of
      dihedral angles, and the conformers accessed in the closed to open transition
      pathways are identified. For these major pathways, a correlation between reaction
      path progress (committors) and the end-to-end distance is identified. A dihedral
      space principal component analysis of the MD trajectory shows that the first
      three modes capture most of the overall fluctuation, and pick out the same four
      dihedrals having essentially all the weight in those modes. A MSM based on root
      mean-square backbone clustering was also carried out, with good agreement found
      with dihedral clustering for the static information, but with results that differ
      significantly for the pathway analysis. 

PMID- 24571786
TI  - Characterization of azithromycin-resistant Neisseria gonorrhoeae isolated in
      Tokyo in 2005-2011.
AB  - A total of 122 Neisseria gonorrhoeae isolated in the Tokyo metropolitan area in
      2005-2011 were collected and analyzed by N. gonorrhoeae multiantigen sequence
      typing (NG-MAST) and for their susceptibility to azithromycin and ceftriaxone.
      All 122 strains were susceptible to ceftriaxone, but 8 strains were azithromycin
      resistant, defined as an azithromycin MIC >= 1 MUg/ml. The 8 azithromycin
      resistant strains were in 6 NG-MAST types, 3 strains in NG-MAST type 1407 and
      each of the other 5 strains in a different NG-MAST type. NG-MAST type 1407
      strains are multidrug-resistant and are disseminated worldwide.

PMID- 24571788
TI  - Regional cortical thinning may be a biological marker for borderline personality
      disorder.
AB  - OBJECTIVE: We investigated cerebral cortical thickness and its relation to
      measurements of difficulties with identifying and describing emotions in patients
      with borderline personality disorder (BPD). METHOD: Eighteen SCID-II-diagnosed
      female patients with BPD and 21 healthy female controls underwent magnetic
      resonance imaging and completed the Toronto Alexithymia Scale (TAS). First,
      regional cortical thickness across the cerebral surface was compared between
      patients and healthy controls. Then, analyses of the association between cortical
      thickness and TAS subscales were performed in patients. RESULTS: Compared with
      controls, patients exhibited clusters of significantly reduced cortical thickness
      in the left medial and lateral prefrontal cortex, left temporoparietal junction,
      bilateral temporal poles, and bilateral paracentral lobules. Significant negative
      associations were observed between cortical thickness and the 'Difficulties
      Describing Feelings' TAS subscale (DDF) scores in patients. The anatomical
      distribution of these associations was highly overlapping with the group
      differences in cortical thickness. CONCLUSION: The pattern of regions exhibiting
      cortical thinning in patients resembles a network of cortical structures
      repeatedly shown to be involved in social cognition. The results of the DDF
      analyses suggest that the thinning may partly be related to interpersonal
      dysfunction in patients with BPD. The pattern of thinning may represent a
      potential biological marker for BPD.

PMID- 24571789
TI  - Vocal complaint in physical education teachers and its association with the
      cardiovascular system.
AB  - BACKGROUND: We examined the vocal complaints and evaluated the correlation
      between the vocal handicap index (VHI) and heart rate variability (HRV) in
      physical education teachers. We evaluated 46 teachers. METHOD: The subjects were
      investigated regarding voice complaint and the VHI was applied. HRV was recorded
      at seated rest for ten minutes and it was analyzed in the time, frequency
      domains, geometric indices and fractal exponents. The three domains of the VHI
      were correlated with the indices of HRV. RESULTS: The physical education teachers
      presented a VHI score much below the standard of the physiological normality.
      There was correlation of the organic domain of the VHI with the NN50 and pNN50
      and correlation of the functional domain and organic domain of the VHI with the
      HF index of HRV. CONCLUSION: The physical education teachers evaluated reported
      vocal complaints that affected their function and it is suggested to be related
      with the cardiac autonomic regulation.

PMID- 24571790
TI  - The influence of culture conditions on the identification of Mycobacterium
      species by MALDI-TOF MS profiling.
AB  - Matrix-assisted laser desorption/ionization-time of flight mass spectrometry
      (MALDI-TOF MS) represents a simple reliable approach for rapid bacterial
      identification based on specific peptide/protein fingerprints. However, cell-wall
      characteristics of mycobacterial species, and their well known stability,
      complicate MALDI-TOF MS profiling analysis. In this study, we tested two recently
      published protocols for inactivation and disruption of mycobacteria, and we also
      examined the influence of different culture conditions (four culture media and
      five cultivation times) on mass spectral quality and the discriminatory power of
      the method. We found a significant influence of sample pretreatment method and
      culture medium on species identification and differentiation for a total of 10
      strains belonging to Mycobacterium phlei and Mycobacterium smegmatis. Optimum
      culture conditions yielding the highest identification success rate against the
      BioTyper database (Bruker Daltonics) and permitting the possibility of automatic
      acquisition of mass spectra were found to be distinct for the two mycobacterial
      species examined. Similarly, individual changes in growth conditions had diverse
      effects on the two species. For these reasons, thorough control over cultivation
      conditions should always be employed to maximize the performance and
      discriminatory power of MALDI-TOF MS profiling, and cultivation conditions must
      be optimized separately for individual groups of mycobacterial species/strains. 

PMID- 24571791
TI  - Primary prevention research in suicide.

PMID- 24571794
TI  - Cellulose paper sensors modified with zwitterionic poly(carboxybetaine) for
      sensing and detection in complex media.
AB  - Poly(carboxybetaine) (PCB) functionalized cellulose paper was used as a paper
      based microfluidic device. The results showed that the PCB modified paper sensor
      was able to achieve (a) more rapid and sensitive glucose detection from undiluted
      human serum compared to bare cellulose and (b) specific antigen detection via
      covalently immobilized antibodies. 

PMID- 24571796
TI  - Patterns and determinants of COPD-related healthcare utilization by severity of
      airway obstruction in Korea.
AB  - BACKGROUND: We investigated patients with chronic obstructive pulmonary disease
      (COPD) to analyze patterns and identify determinants of healthcare use, according
      to the severity of airflow obstruction. We used retrospective cohort data from a
      combination of the 4th Korea National Health and Nutritional Examination Survey
      (KNHANES) and Korean National Health Insurance (NHI) claims. METHODS: Demographic
      and medical claims data were retrospectively analyzed from the 4th KNHANES along
      with NHI claims. Eligible patients were aged >=40 years, who underwent complete
      pulmonary function tests (PFTs), and had at least one inpatient or outpatient
      claim coded as COPD between January 1, 2007 and December 31, 2010. RESULTS: Among
      6,663 eligible participants, 897 (13.5%) had airway obstruction. Self-reported
      physician-diagnosed COPD comprised only 3%, and there were 870 undiagnosed COPD
      patients (97%). Self-reported physician-diagnosed asthma made up 3.7%. Of the 897
      respondents, 244 (27.2%) used COPD-related healthcare services. The frequency of
      healthcare visits increased with increasing severity of airway obstruction. After
      a 3-year follow-up period, 646 (74.2% of those initially undiagnosed) remained
      undiagnosed and only 224 (25.8%) were diagnosed and treated for COPD. Only 27.5%
      of the 244 participants with airway obstruction who used COPD-related healthcare
      underwent PFTs during the study period. The percentage of prescribed medications
      associated with COPD increased in accordance with the severity of the COPD.
      Inhaled long-acting anticholinergics were prescribed for 10.9% of patients with
      moderate airway obstruction and for 52.4% of patients with severe obstruction.
      Inhaled long-acting beta-agonists combined with corticosteroids were prescribed
      for 50% of patients with severe airway obstruction. Conversely, 44.6% of
      healthcare users were prescribed oral theophylline for COPD treatment, and 21.7%
      were also prescribed an oral corticosteroid. The determinants of COPD-associated
      healthcare use in respondents with obstructive lung disease were advanced age,
      severe airflow limitation, presence of comorbidities, and self-reported physician
      diagnosis of COPD. CONCLUSIONS: This study ascertained marked underdiagnosed
      COPD. Although the percentage of prescribed medication used to treat COPD
      increased with the severity of the COPD, medications primarily prescribed such as
      oral theophylline or oral corticosteroids are inappropriate for first-line COPD
      treatment.

PMID- 24571798
TI  - Anticancer activity of five forest crops used in African folklore:
      antiproliferative and pro-apoptotic effects.
AB  - Acalypha wilkesiana, Caesalpinia bonduc, Jatropha multifida, Momordica charantia
      and Picralima nitida used in African folklore for treating cancer were
      investigated. All extracts except J. multifida resulted in no significant
      alteration in cell cycle distribution and apoptosis in MCF-7 and BT-20. The J.
      multifilda (JMR-Ch) caused cell cycle arrest at G1 checkpoint and apoptosis in
      MCF-7. Slight changes in the integrin expression of MCF-7 after treatment with 1
      and 10 MUg/mL of JMR-Ch were observed. Fluorescence-activated confocal microscopy
      shows changes in cell morphology and beta1 integrin localisation within MCF-7
      cells after exposure to 10 and 25 MUg/mL of JMR-Ch. JMR-Ch (1 MUg/mL) treatment
      resulted in time-dependent decrease in cell acidification and respiration in MCF
      7 cells and a time-dependent decrease in BT-20 cell respiration, while in MCF
      10A, there was an enhancement of acidification. These results revealed the
      probable application of JMR-Ch in cancer therapy.

PMID- 24571801
TI  - KHA-CARI guideline: KHA-CARI adaptation of the KDIGO Clinical Practice Guideline
      for Acute Kidney Injury.

PMID- 24571800
TI  - Imaging and management of a small cell lung cancer metastasis/adrenal adenoma
      collision tumor: a case report and review of the literature.
AB  - OBJECTIVE: We report a case of an adrenal collision tumor composed of a small
      cell lung carcinoma metastasis and a benign adrenal adenoma identified
      preoperatively on FDG-PET, CT and MRI and confirmed pathologically. METHODS: The
      patient's history, preoperative imaging characteristics, postoperative course,
      and histopathology are described. A review of the literature addressing adrenal
      collision tumors is provided. RESULTS: A 47-year-old female was found to have a
      left upper lobe lung mass and an adrenal lesion on imaging. FDG-PET, CT and MRI
      of the adrenal suggested a metastatic lesion adjacent to an adrenal adenoma. CT
      guided biopsy of the adrenal gland was consistent with a small cell lung cancer
      metastasis. The patient underwent systemic chemotherapy and had complete
      resolution of the left upper lobe mass. Post-treatment FDG-PET demonstrated a
      persistently enlarged adrenal gland with decreased but persistent FDG uptake. The
      patient underwent adrenalectomy and pathologic examination demonstrated a small
      cell lung cancer/adenoma collision tumor. CONCLUSIONS: This case and a review of
      the literature demonstrate that FDG, CT and MR imaging can all characterize the
      separate components of collision tumors within the adrenal gland.

PMID- 24571799
TI  - What is the role of obesity in the aetiology of arsenic-related disease?
AB  - Consumption of arsenic contaminated drinking water causes a large variety of
      adverse health outcomes. Body mass index (BMI), which is linked to diet, is
      positively associated with arsenic methylation capacity. We investigated the
      association between an obesity-related diet and arsenic body burden from exposure
      to naturally contaminated drinking water among Nova Scotia residents. We
      collected home drinking water and toenail clipping samples among 960 men and
      women aged 35 to 69 years in Nova Scotia, Canada from 2009 through 2010. We
      measured body composition and arsenic concentrations in drinking water and
      toenails clipping samples and collected socio-demographic, behavioural, and
      dietary information via standardized questionnaires. We derived an obesity
      related dietary pattern score using reduced rank regression. Across quartiles of
      the obesity-related dietary pattern score there were no significant differences
      in drinking water arsenic concentrations, but there was an inverse trend in
      arsenic concentrations in toenails across the dietary pattern score (P=0.01).
      Compared with individuals in the first quartile of the dietary pattern score,
      those in the second through fourth quartiles had decreased likelihoods of high
      toenail arsenic (>= 85 percentile). The corresponding odds ratios (95% confidence
      intervals [CI]) were 0.81 (95% CI, 0.49, 1.36), 0.57 (95% CI, 0.33, 0.99), and
      0.55 (95% CI, 0.31, 0.98), respectively (P for trend=0.02). We conclude that
      given similar levels of naturally occurring arsenic exposure via drinking water,
      an obesity-related dietary pattern was associated with significantly lower
      arsenic concentrations in toenails. Further studies to investigate the
      underlining mechanisms are warranted.

PMID- 24571797
TI  - Whole blood assay and visceral leishmaniasis: Challenges and promises.
AB  - For years, the ability to study immune responses in patients with active visceral
      leishmaniasis (VL) has been hampered by the absence of detectable antigen
      specific Th1 responses using cells from peripheral blood mononuclear cells
      (PBMCs). Employing whole blood assay (WBA), we recently reported that whole blood
      cells of active VL patients maintain the capacity to secrete significant levels
      of antigen driven IFN-gamma and IL-10. Furthermore, WBA that uses soluble
      leishmania antigen (SLA) have advantages over the leishmanin skin test (LST), in
      terms of higher specificity and better correlation with surrogate markers of
      exposures to Leishmania donovani. These findings open the door to a series of
      immunological and epidemiological studies not previously possible for VL. In the
      present review, we discuss current status, future perspectives as well as
      obstacles in the research on WBA. Research in this area is essential for
      development of potential immunological and epidemiological tools for VL.

PMID- 24571802
TI  - Hydrogen passivation of impurities in Al(2)O(3).
AB  - Carbon and nitrogen are contaminant impurities in Al2O3 dielectrics grown by
      atomic layer deposition, leading to deleterious effects in device performance. We
      investigate whether these impurities can be passivated using hydrogen. The role
      of atomic hydrogen in the electronic properties is addressed by examining
      formation energies and charge-state transition levels of C-H and N-H complexes.
      Combined with calculated band alignment, we then assess the impact on
      Al2O3/semiconductor interfaces. We find that hydrogen is indeed an effective
      passivating agent: it removes carbon-related carrier traps and passivates
      negative fixed charge associated with nitrogen. 

PMID- 24571803
TI  - Context-based features enhance protein secondary structure prediction accuracy.
AB  - We report a new approach of using statistical context-based scores as encoded
      features to train neural networks to achieve secondary structure prediction
      accuracy improvement. The context-based scores are pseudo-potentials derived by
      evaluating statistical, high-order inter-residue interactions, which estimate the
      favorability of a residue adopting certain secondary structure conformation
      within its amino acid environment. Encoding these context-based scores as
      important training and prediction features provides a way to address a long
      standing difficulty in neural network-based secondary structure predictions of
      taking interdependency among secondary structures of neighboring residues into
      account. Our computational results have shown that the context-based scores are
      effective features to enhance the prediction accuracy of secondary structure
      predictions. An overall 7-fold cross-validated Q3 accuracy of 82.74% and Segment
      Overlap Accuracy (SOV) accuracy of 86.25% are achieved on a set of more than 7987
      protein chains with, at most, 25% sequence identity. The Q3 prediction accuracy
      on benchmarks of CB513, Manesh215, Carugo338, as well as CASP9 protein chains is
      higher than popularly used secondary structure prediction servers, including
      Psipred, Profphd, Jpred, Porter (ab initio), and Netsurf. More significant
      improvement is observed in the SOV accuracy, where more than 4% enhancement is
      observed, compared to the server with the best SOV accuracy. A Q8 accuracy of
      >70% (71.5%) is also found in eight-state secondary structure prediction. The
      majority of the Q3 accuracy improvement is contributed from correctly identifying
      beta-sheets and alpha-helices. When the context-based scores are incorporated,
      there are 15.5% more residues predicted with >90% confidence. These high
      confidence predictions usually have a rather high accuracy (averagely ~95%). The
      three- and eight-state prediction servers (SCORPION) implementing our methods are
      available online.

PMID- 24571805
TI  - Neisseria meningitidis serogroup W, Burkina Faso, 2012.
AB  - In 2010, Burkina Faso became the first country to introduce meningococcal
      serogroup A conjugate vaccine (PsA-TT). During 2012, Burkina Faso reported
      increases in Neisseria meningitidis serogroup W, raising questions about whether
      these cases were a natural increase in disease or resulted from serogroup
      replacement after PsA-TT introduction. We analyzed national surveillance data to
      describe the epidemiology of serogroup W and genotyped 61 serogroup W isolates.
      In 2012, a total of 5,807 meningitis cases were reported through enhanced
      surveillance, of which 2,353 (41%) were laboratory confirmed. The predominant
      organism identified was N. meningitidis serogroup W (62%), and all serogroup W
      isolates characterized belonged to clonal complex 11. Although additional years
      of data are needed before we can understand the epidemiology of serogroup W after
      PsA-TT introduction, these data suggest that serogroup W will remain a major
      cause of sporadic disease and has epidemic potential, underscoring the need to
      maintain high-quality case-based meningitis surveillance after PsA-TT
      introduction. 

PMID- 24571806
TI  - Risks of neurobehavioral teratogenicity associated with prenatal exposure to
      valproate monotherapy: a systematic review with regulatory repercussions.
AB  - Beyond its formal indications (epilepsy, bipolar disorder, and migraine),
      valproate sodium (VPA) is widely used in a number of other clinical conditions.
      Recently, however, the U.S. Food and Drug Administration (FDA) issued a warning
      regarding a decrease in IQ scores in children prenatally exposed to the drug. For
      patients with migraine, the pregnancy labeling of VPA will be changed from
      Category "D" to "X." VPA products will remain in pregnancy category "D" for
      treating epilepsy and manic episodes associated with bipolar disorder. Thus, this
      article aims to assess (through a computerized Medline/PubMed search) the
      neurobehavioral teratogenicity of valproate monotherapy, in order to evaluate
      alternative regulatory decisions. Reviewed information suggests a detrimental
      impact of antenatal valproate exposure on the global child neurodevelopment.
      Affected areas include not just reduced IQ scores, but also behavioral problems
      and a potential increase in the risk for a future diagnosis of attention
      deficit/hyperactivity disorder. An increased risk of developing autism-spectrum
      disorders has also been reported. Thus, in my opinion, VPA should be assigned
      definitively to the Category "X," independent of any considerations about its
      clinical indications, and should be strictly avoided during pregnancy, due to the
      demonstrated risk of both neurobehavioral and neurocognitive teratogenicity. 

PMID- 24571804
TI  - Involved-field irradiation in definitive chemoradiotherapy for locally advanced
      esophageal squamous cell carcinoma.
AB  - BACKGROUND: Since there is high local failure and poor survival for unresectable
      esophageal squamous cell carcinoma (ESCC), the necessity of elective node
      irradiation is controversial. The purpose of this study was to investigate the
      failure patterns and survival in patients with locally advanced ESCC receiving
      involved-field irradiation (IFI). METHODS: A retrospective study was preformed on
      the clinical records of patients with locally advanced ESCC, who have received
      IFI with concurrent chemotherapy between January 2003 and January 2009. Comparing
      the target volume and first sites of failure, patterns of failure were defined as
      in-field, out-of-field regional lymph node and distant failure. The survivals
      were analyzed by different patterns of failure. RESULTS: Eighty patients were
      included in our study. With a median follow-up of 52.6 months, failures were
      observed in 76 patients. In-field recurrence, distant metastasis, and out-of
      field regional failure were seen in 53.75%, 41.25%, 30% patients, respectively.
      There were significant differences in OS for patients with and without in-field
      (median OS 14.2 vs.17.4 m, P=0.01)or distant failure(13.2 vs.15.9 m, P <=
      0.0001), but not for out-of-field regional lymph node failure(both 14.5 m,
      P=0.665). CONCLUSIONS: The solitary regional nodal failure of out-of-field was
      acceptable in advanced ESCC patients treated with IFI. In-field and distant
      failures remained the predominant patterns and negatively impacted survival more
      significantly. Further investigation is needed to establish the optimal
      radiotherapy field for these patients at advanced stage.

PMID- 24571807
TI  - What was learned: studies by the consortium for research in ECT (CORE) 1997-2011.
AB  - OBJECTIVE: To review the findings of the four-hospital collaborative studies of
      electroconvulsive therapy (ECT) in unipolar depressed patients known as CORE
      between 1997 and 2011. Unipolar depressed patients were treated with bilateral
      ECT, and on remission were randomly assigned to a fixed schedule continuation ECT
      or to combined lithium and nortriptyline for 6 months. A second study compared
      three electrode placements in unipolar and bipolar depressed patients. METHOD:
      Nineteen published reports were reviewed. The findings are compared with those of
      a parallel multi-hospital study of ECT led by a Columbia University Collaboration
      (CUC) team that studied right unilateral ECT in a similar population with similar
      inclusion/exclusion and remission criteria. Successful ECT was followed by
      placebo, nortriptyline alone, or combined lithium, and nortriptyline. RESULTS:
      Relapse rates after remission were similar with fixed schedule ECT as with
      medications. Predictors of outcome (psychosis, suicide risk, polarity,
      melancholia, atypical depression, age) and technical aspects (electrode
      placement, seizure threshold, speed of response) are discussed, CONCLUSION: The
      findings offer criteria to optimize the selection of patients, the technique, and
      outcome of ECT for unipolar and bipolar depressed patients. Continuation ECT is
      an effective alternative to continuation treatment with lithium and
      nortriptyline. Bilateral electrode placement is more efficient than alternative
      placements. ECT relieves both bipolar and unipolar depression.

PMID- 24571808
TI  - Efficacy of pre-surgical axitinib for shrinkage of inferior vena cava thrombus in
      a patient with advanced renal cell carcinoma.
AB  - The authors present the first case report of pre-surgical axitinib treatment on
      primary renal tumor and vena cava thrombus. We report the case of a 78-year-old
      woman with renal cell carcinoma and inferior vena cava tumor thrombus,
      successfully downstaged with pre-surgical therapy with axitinib. A significant
      objective response was observed for tumor size and thrombus. After initiation of
      axitinib therapy, computed tomography showed a decrease, from 57 to 51 mm, in the
      maximal renal tumor diameter. The tumor thrombus had shortened to 42 mm and had
      moved to the inferior hepatic vein (Levels 4-3), thereby obviating the need for
      thoracotomy. The patient finally accepted surgical treatment. Our case was
      enabled to perform less surgery for advanced renal cell carcinoma with tumor
      thrombus using axitinib as a pre-surgical therapy. 

PMID- 24571809
TI  - Overweight, obesity and related conditions: a cross-sectional study of adult
      inpatients at a Norwegian hospital.
AB  - BACKGROUND: Overweight, obesity and associated conditions are major public health
      concerns in Norway. The prevalence of overweight and obesity in the general
      population in Norway is increasing, but there are limited data on how the
      situation is in hospitals. This study aimed to find the prevalence of overweight
      and obesity, and explore the associations of overweight, obesity and its related
      medical conditions in an adult in-patient sample at specified somatic and
      psychiatric departments at St. Olavs Hospital, Trondheim. RESULTS: A total of 497
      patients participated. The mean BMI for the total sample at screening was 25.4
      kg/m2. The prevalence of overweight and obesity was 45.1%. There was a higher
      association of overweight and obesity among patients aged 40-59 years (OR: 1.7)
      compared to those being younger. There was no significant difference between the
      somatic and the psychiatric samples. In the somatic sample overweight and obesity
      was associated with obesity-related conditions for both genders (OR: 2.0 and 2.1,
      respectively), when adjusted for age. CONCLUSION: The substantial prevalence of
      overweight and obese patients may pose a threat to future hospital services. To
      further address the burden of overweight and obesity in hospitals, we need more
      knowledge about consequences of length of stay, use of resources and overall
      cost.

PMID- 24571811
TI  - Dual binding site assisted chromogenic and fluorogenic recognition and
      discrimination of fluoride and cyanide by a peripherally borylated
      metalloporphyrin: overcoming anion interference in organoboron based sensors.
AB  - Peripherally triarylborane decorated porphyrin (2) and its Zn(II) complex (3)
      have been synthesized. Compound 3 contains of two different Lewis acidic binding
      sites (Zn(II) and boron center). Unlike all previously known triarylborane based
      sensors, the optical responses of 3 toward fluoride and cyanide are distinctively
      different, thus enabling the discrimination of these two interfering anions.
      Metalloporphyrin 3 shows a multiple channel fluorogenic response toward fluoride
      and cyanide and also a selective visual colorimetric response toward cyanide. By
      comparison with model systems and from detailed photophysical studies on 2 and 3,
      we conclude that the preferential binding of fluoride occurs at the peripheral
      borane moieties resulting in the cessation of the EET (electronic energy
      transfer) process from borane to porphyrin core and with negligible negetive
      cooperative effects. On the other hand, cyanide binding occurs at the Zn(II) core
      leading to drastic changes in its absorption behavior which can be followed by
      the naked eye. Such changes are not observed when the boryl substituent is absent
      (e.g., Zn-TPP and TPP). Compounds 2 and 3 were also found to be capable of
      extracting fluoride from aqueous medium. 

PMID- 24571812
TI  - Vitamin D receptor ApaI gene polymorphism and tuberculosis susceptibility: a meta
      analysis.
AB  - AIM: Vitamin D performs its actions through the vitamin D receptor (VDR), which
      acts as a transcriptional factor. Many case-control studies have been performed
      in the past to elucidate the association of the ApaI polymorphism of VDR gene and
      the risk of tuberculosis (TB). However, these studies have shown inconsistent and
      conflicting results. In the present study, a meta-analysis was performed to
      investigate the potential relationship between the VDR ApaI gene polymorphism and
      the risk of TB. METHODOLOGY: A quantitative synthesis was performed for the
      published studies based on the association between the VDR ApaI gene polymorphism
      and the risk of TB retrieved from PubMed (Medline) and EMBASE web databases. A
      meta-analysis was performed, and pooled odds ratios (ORs) and 95% confidence
      intervals (95% CIs) were calculated for all the genetic models. RESULTS: We
      observed a decreased risk of TB in allelic contrast (a vs. A: p=0.009; OR=0.869,
      95% CI=0.782 to 0.965), homozygous (aa vs. AA: p=0.006; OR=0.724, 95% CI=0.575 to
      0.910), and heterozygous (aA vs. AA: p=0.698; OR=0.948, 95% CI=0.722 to 1.243)
      comparisons. Similarly, dominant (aa+Aa vs. AA: p=0.032; OR=0.842, 95% CI=0.720
      to 0.985) and recessive (aa vs. AA+Aa: p=0.027; OR=0.796, 95% CI=0.650 to 0.975)
      models also demonstrated a decreased risk of TB, whereas a heterozygous genotype
      (Aa vs. AA: p=0.109; OR=0.873, 95% CI=0.740 to 1.030) did not indicate any
      association with the risk of TB. There was no evidence of publication bias and
      heterogeneity test. CONCLUSIONS: This meta-analysis suggests that ApaI
      polymorphism of the VDR gene is significantly associated with a decreased risk of
      TB. However, future larger studies with groups of populations are warranted to
      analyze this association.

PMID- 24571810
TI  - The LWDS-10J: reliability and validity of the Lebanon Waterpipe Dependence Scale
      among university students in Jordan.
AB  - INTRODUCTION: While the Lebanon Waterpipe Dependence Scale (LWDS-11) has shown
      promise in assessing dependence on waterpipe tobacco smoking (WTS) in Lebanon
      among adult users, it would be valuable to identify WTS addiction earlier and to
      explore reliability and validity of these items in other populations. METHODS: In
      2010-2012, we conducted a multiyear survey of 5,853 students from 4 Jordanian
      universities. We measured WTS, sociodemographic data, and the LWDS-11 items. We
      conducted exploratory factor analysis with half of the sample and confirmed the
      resulting model using confirmatory factor analysis with the other half. We
      examined construct validity with regression models assessing associations between
      the modified scale and 5 constructs conceptually expected to be associated with
      dependence. RESULTS: WTS rates were 35% in the past 30 days and 56% ever.
      Principal-components analysis of LWDS items in the first half of the sample
      yielded 10 items representing 3 factors labeled physical dependence,
      relaxation/pleasure, and social aspects. Cronbach's alpha was .77 for the total
      scale and was .75, .70, and .67 for each individual subscale. Confirmatory factor
      analysis in a structural equation modeling framework confirmed good fit (root
      mean squared error of approximation = 0.068, and comparative fit index = 0.937).
      Dependence according to the resulting scale (LWDS-10J) was strongly associated
      with each of the 5 expected constructs, whether the dependent variable was
      treated as categorical or continuous. CONCLUSIONS: The LWDS-11 items exhibited a
      different factor structure in our sample. However, the modified scale (LWDS-10J)
      showed promising reliability and construct validity in this population.

PMID- 24571813
TI  - [DSM-5-the revisions and their implications for child and adolescent psychiatry].

PMID- 24571814
TI  - [Association of peer victimization, coping, and pathological internet use among
      adolescents].
AB  - OBJECTIVE: To investigate the association of pathological internet use, peer
      victimization, and coping styles among German adolescents who reported
      experiences of peer victimization. METHOD: A cross-sectional survey was conducted
      within the framework of a European school-based study (SEYLE) which included 1357
      representative students (female/male: 710/647; mean age: 14.7; SD = 0.80) from
      Germany. Pathological internet use was assessed by the Young Diagnostic
      Questionnaire. Peer victimization was classified into verbal, physical, and
      relational. Coping style was divided into active, avoidance, help-seeking, and
      other. Psychological symptoms were assessed as covariate by the Strengths and
      Difficulties Questionnaire. RESULTS: 4.8 % of the students showed pathological
      internet use, 14.4 % presented with problematic internet use. 52.3 % of the
      adolescents reported peer victimization (38.7 % verbal victimization, 19.8 %
      physical victimization, 34.1 % relational victimization). There was a significant
      association of peer victimization with pathological internet use, which could
      partly be explained by psychological symptoms. Normal, problematic, und
      pathological internet users did not differ with regard to their coping styles in
      relation to victimization. CONCLUSIONS: There is an association between peer
      victimization, psychological symptoms, and pathological internet use. School- and
      family-based prevention programs and evaluated therapies are needed.

PMID- 24571815
TI  - [Female conduct disorders].
AB  - The last few years have seen much research on girls with conduct disorder (CD).
      This article summarizes the gender-specific data regarding prevalence,
      differences with respect to symptomatology (e.g., subtypes of aggression, callous
      unemotional (cu)-traits), and it presents data on the autonomic and
      neuroendocrine stress system as well as genetic, neurocognitive, and neuroimaging
      data. Differences in the impact of environmental factors on boys and girls for
      the development of CD are discussed. Taken together, the data indicate that there
      is great overlap in symptomatology, personality traits, and neurobiological
      aberrations in girls and boys with CD. Since fewer girls than boys exhibit CD
      symptomatology, further investigations on CD in girls might help to identify
      resilience factors that could improve future therapeutic interventions. 

PMID- 24571816
TI  - [Classification of enuresis/encopresis according to DSM-5].
AB  - Elimination disorders are common in childhood and adolescence. Enuresis is
      traditionally defined as wetting from the age of 5 years and encopresis as
      soiling from 4 years onwards - after all organic causes have been excluded. In
      the past decades, many subtypes of elimination disorders have been identified
      with different symptoms, etiologies, and specific treatment options.
      Unfortunately, the DSM-5 criteria did not integrate these new approaches. In
      contrast, classification systems of the International Children's Incontinence
      Society (ICCS) for enuresis and urinary incontinence as well as the ROME-III
      criteria for fecal incontinence offer new and relevant suggestions for both
      clinical and research purposes. 

PMID- 24571817
TI  - [Substance-related and addictive disorders in the DSM-5].
AB  - This paper concerns the revised classification of Substance-Related and Addictive
      Disorders in the fifth edition of the American Psychiatric Association's (APA)
      Diagnostic and Statistical Manual of Mental Disorders (DSM-5). In DSM-5,
      substance use disorders are diagnosed on a continuum of severity specified by
      explicit operationalized diagnostic criteria. "Gambling disorder" is the only
      behavioral addiction added to the DSM. Furthermore, preliminary criteria for
      "Caffeine Use Disorder" and "Internet Gaming Disorder" have now been defined in
      the manual. Adopting the DSM-5 criteria catalogue within the German treatment
      system for children and adolescents with substance use disorders or at risk for
      developing substance use disorders would be of great significance. Since the
      diagnostic threshold is lower, more patients would be eligible for treatment.
      Thus, early intervention in the area of substance use disorders should be
      strengthened, a development that appears to be highly desirable from the
      perspective of child and adolescent psychiatry. The current Section III
      diagnoses, with their now comprehensive diagnostic criteria, facilitate more
      internationally compatible research. 

PMID- 24571818
TI  - [Obsessive-compulsive disorders in DSM-5 - what is new?].
AB  - Obsessive-compulsive disorders are a frequent and debilitating condition also in
      children and adolescents. The present paper summarizes the changes in the DSM
      diagnostic criteria between the IV-TR edition and the DSM-5 edition, and
      evaluates them critically. A central feature is the revision of the category to
      which these disorders belong: Obsessive-Compulsive Disorders are no longer
      considered to be anxiety disorders, but rather now comprise an independent
      category encompassing a broader spectrum of obsessive-compulsive and related
      disorders. Minor changes have been made to the description of the criteria, and
      there is a new emphasis on the clinical assessment of the patient's insight level
      (good, poor, absent). Obsessive-compulsive disorders associated with tic
      disorders are classified as a separate subtype. The present paper discusses these
      changes on the basis of the available studies and literature, and then looks
      ahead to the implementation of the new criteria in the everyday clinical setting
      and in research. 

PMID- 24571819
TI  - [Tourette syndrome and other tic disorders in DSM-5 - a comment].
AB  - The classification of tic disorders has been revised in the new fifth edition of
      the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). The previously
      expressed suggestion to categorize tic disorders within the "Anxiety and
      Obsessive Compulsive Disorders" was not implemented. The section "Disorders
      Usually First Diagnosed in Infancy, Childhood, or Adolescence" was revised and
      renamed as "Neurodevelopmental Disorders." Tic disorders are classified there as
      movement disorders. Most of the changes are distinct improvements from both a
      clinical and a scientific perspective. For example, by removing the adjective
      "stereotype," the definition of tics is more precise and unified. Also, the new
      time-oriented criteria are more practical in the clinical setting, e.g., the
      exclusion criterion of a tic-free interval more than 3 months given for chronic
      tic disorders has been deleted. The renamings from "Transient" to "Provisional
      Tic Disorder" as well as from "Chronic" to "Persistent Tic Disorder" are welcome
      changes from a clinical perspective. Overall, the revision of the criteria is an
      important step towards providing more clarity and feasibility. However, the
      revised classification of tic disorders is still based only on clinical
      experience and not on evidence. Future studies should show whether the revised
      and improved criteria truly provide the optimal classification. 

PMID- 24571820
TI  - [Development of the new model of continuing education in child and adolescent
      psychiatry, psychosomatic medicine and psychotherapy and the national medical
      learning goals catalog].

PMID- 24571823
TI  - Drug-refractory aggression, self-injurious behavior, and severe tantrums in
      autism spectrum disorders: a chart review study.
AB  - Aggression, self-injurious behavior, and severe tantrums are impairing symptoms
      frequently experienced by individuals with autism spectrum disorders. Despite US
      Food and Drug Administration approval of two atypical antipsychotics targeting
      these symptoms in youth with autistic disorder, they remain frequently drug
      refractory. We define drug-refractory aggression, self-injurious behavior, and
      severe tantrums in people with autism spectrum disorders as behavioral symptoms
      requiring medication adjustment despite previous trials of risperidone and
      aripiprazole or previous trials of three psychotropic drugs targeting the symptom
      cluster, one of which was risperidone or aripiprazole. We reviewed the medical
      records of individuals of all ages referred to our clinic for autism spectrum
      disorder diagnostic evaluation, as well as pharmacotherapy follow-up notes for
      all people meeting autism spectrum disorder criteria, for drug-refractory
      symptoms. Among 250 consecutively referred individuals, 135 met autism spectrum
      disorder and enrollment criteria, and 53 of these individuals met drug-refractory
      symptom criteria. Factors associated with drug-refractory symptoms included age
      12 years or older (p < 0.0001), diagnosis of autistic disorder (p = 0.0139), and
      presence of intellectual disability (p = 0.0273). This pilot report underscores
      the significance of drug-refractory aggression, self-injurious behavior, and
      severe tantrums; suggests the need for future study clarifying factors related to
      symptom development; and identifies the need for focused treatment study of this
      impairing symptom domain. 

PMID- 24571825
TI  - Improved efficiency of a large-area Cu(In,Ga)Se2 solar cell by a nontoxic
      hydrogen-assisted solid Se vapor selenization process.
AB  - A nontoxic hydrogen-assisted solid Se vapor selenization process (HASVS)
      technique to achieve a large-area (40 * 30 cm(2)) Cu(In,Ga)Se2 (CIGS) solar panel
      with enhanced efficiencies from 7.1 to 10.8% (12.0% for active area) was
      demonstrated. The remarkable improvement of efficiency and fill factor comes from
      improved open circuit voltage (Voc) and reduced dark current due to (1) decreased
      interface recombination raised from the formation of a widened buried
      homojunction with n-type Cd(Cu) participation and (2) enhanced separation of
      electron and hole carriers resulting from the accumulation of Na atoms on the
      surface of the CIGS film. The effects of microstructural, compositional, and
      electrical characteristics with hydrogen-assisted Se vapor selenization,
      including interdiffusion of atoms and formation of buried homojunction, were
      examined in detail. This methodology can be also applied to CIS (CuInSe2) thin
      film solar cells with enhanced efficiencies from 5.3% to 8.5% (9.4% for active
      area) and provides a facile approach to improve quality of CIGS and stimulate the
      nontoxic progress in the large scale CIGS PV industry.

PMID- 24571824
TI  - Efficacy of a physiotherapy rehabilitation program for individuals undergoing
      arthroscopic management of femoroacetabular impingement - the FAIR trial: a
      randomised controlled trial protocol.
AB  - BACKGROUND: Femoroacetabular impingement is a common cause of hip/groin symptoms
      and impaired functional performance in younger sporting populations and results
      from morphological abnormalities of the hip in which the proximal femur abuts
      against the acetabular rim. Many people with symptomatic femoroacetabular
      impingement undergo arthroscopic hip surgery to correct the bony abnormalities.
      While many case series over the past decade have reported favourable surgical
      outcomes, it is not known whether formal rehabilitation is needed as part of the
      management of patients undergoing this surgical procedure. This randomised
      controlled trial will investigate the efficacy of a progressive physiotherapist
      supervised rehabilitation program (Takla-O'Donnell Protocol) in improving health
      related quality of life, physical function and symptoms in individuals undergoing
      arthroscopic management of femoroacetabular impingement. METHODS/DESIGN: 100
      people aged 16-35 years undergoing hip arthroscopy for symptomatic
      femoroacetabular impingement will be recruited from surgical practices in
      Melbourne, Australia and randomly allocated to either a physiotherapy or control
      group. Both groups will receive written information and one standardised post
      operative physiotherapy visit whilst in hospital as per usual care. Those in the
      physiotherapy group will also receive seven individual 30-minute physiotherapy
      sessions, including one pre-operative visit (within 2 weeks of surgery) and six
      post-operative visits at fortnightly intervals (commencing two weeks after
      surgery). The physiotherapy intervention will incorporate education and advice,
      manual techniques and prescription of a progressive rehabilitation program
      including home, aquatic and gym exercises. The control group will not receive
      additional physiotherapy management. Measurements will be taken at baseline (2
      weeks pre-operatively) and at 14 and 24 weeks post-surgery. Primary outcomes are
      the International Hip Outcome Tool and the sports subscale of the Hip Outcome
      Score at 14 weeks post-surgery. Secondary outcomes include the Copenhagen Hip and
      Groin Outcome Score, the activities of daily living subscale of the Hip Outcome
      Score, the Heidelberg Sports Activity Score, a modified Tegner Activity Scale and
      participant-perceived overall change. DISCUSSION: The findings from this
      randomised controlled trial will provide evidence for the efficacy of a specific
      physiotherapist-supervised rehabilitation program in improving outcomes following
      arthroscopic management of symptomatic femoroacetabular impingement. TRIAL
      REGISTRATION: Australian New Zealand Clinical Trials Registry reference number:
      ACTRN12613000282785.

PMID- 24571827
TI  - Epidemiology and outcome of community-acquired acute kidney injury.
AB  - AIMS: Very little data exist regarding community-acquired acute renal injury (CA
      AKI). We have identified and characterized a patient cohort with CA-AKI, and
      documented its impact on renal function and patient mortality. METHODS: Using the
      database of the Medical Biochemistry Department of the Cardiff and Vale
      University Health Board we identified all patients with CA-AKI over a 1 month
      period in 2009. Follow-up biochemical and clinical data were used to determine
      short-term (3 months) and long-term (3 years) outcomes. Comparisons were made to
      a random and an age/sex matched group. RESULTS: Patients with CA-AKI were older
      than a non-AKI cohort (70.3 vs 57.1 years; P < 0.0001), with a 61% male
      predominance. 38% had pre-existing chronic kidney disease (CKD) compared with 25%
      in the age- and sex-matched non-CA-AKI cohort (P = 0.007). 54% of CA-AKI were
      admitted for inpatient care. Admission was associated with a higher incidence of
      complete recovery of renal function. Mortality at 3 months was 16.5%, and was
      related to the severity of AKI. Over the 3 years of follow-up 71% of patients
      with CA-AKI developed progressive CKD which was more likely following
      incomplete/no recovery of renal function and in the context of pre-existing CKD.
      Three year mortality was 45%, which was higher than that of the age/sex matched
      control cohort (15.7%; P < 0.0001), but was not related to the development of
      progressive CKD. CONCLUSIONS: CA-AKI carries significant implications in terms of
      both development of progressive renal disease and high long-term patient
      mortality.

PMID- 24571826
TI  - Placement, support, and retention of health professionals: national, cross
      sectional findings from medical and dental community service officers in South
      Africa.
AB  - BACKGROUND: In South Africa, community service following medical training serves
      as a mechanism for equitable distribution of health professionals and their
      professional development. Community service officers are required to contribute a
      year towards serving in a public health facility while receiving supervision and
      remuneration. Although the South African community service programme has been in
      effect since 1998, little is known about how placement and practical support
      occur, or how community service may impact future retention of health
      professionals. METHODS: National, cross-sectional data were collected from
      community service officers who served during 2009 using a structured self-report
      questionnaire. A Supervision Satisfaction Scale (SSS) was created by summing
      scores of five questions rated on a three-point Likert scale (orientation,
      clinical advising, ongoing mentorship, accessibility of clinic leadership, and
      handling of community service officers' concerns). Research endpoints were guided
      by community service programmatic goals and analysed as dichotomous outcomes.
      Bivariate and multivariate logistical regressions were conducted using Stata 12.
      RESULTS: The sample population comprised 685 doctors and dentists (response rate
      44%). Rural placement was more likely among unmarried, male, and black
      practitioners. Rates of self-reported professional development were high (470 out
      of 539 responses; 87%). Participants with higher scores on the SSS were more
      likely to report professional development. Although few participants planned to
      continue work in rural, underserved communities (n = 171 out of 657 responses,
      25%), those serving in a rural facility during the community service year had
      higher intentions of continuing rural work. Those reporting professional
      development during the community service year were twice as likely to report
      intentions to remain in rural, underserved communities. CONCLUSIONS: Despite
      challenges in equitable distribution of practitioners, participant satisfaction
      with the compulsory community service programme appears to be high among those
      who responded to a 2009 questionnaire. These data offer a starting point for
      designing programmes and policies that better meet the health needs of the South
      African population through more appropriate human resource management. An
      emphasis on professional development and supervision is crucial if South Africa
      is to build practitioner skills, equitably distribute health professionals, and
      retain the medical workforce in rural, underserved areas.

PMID- 24571828
TI  - The psychopharmacology of violence: making sensible decisions.
AB  - Violent behavior associated with mental disorders is a common reason for
      admission to a psychiatric inpatient unit. Once hospitalized, patients may
      continue to be intermittently agitated and have persistent aggressive behaviors,
      preventing their discharge back into the community. Managing agitation quickly
      with effective pharmacological agents can avoid further escalation to aggression
      and violence. In the acute setting, this usually involves the parenteral use of
      antipsychotics, with or without benzodiazepines. Within the past decade, short
      acting intramuscular formulations of second-generation antipsychotics have become
      available and provide a means to induce calm with a substantially lower risk of
      acute dystonia or akathisia compared with haloperidol. New alternative
      formulations that avoid injections include inhalation and sublingual
      administration. Longer-term management of persistent aggressive behavior by
      reducing the frequency and intensity of future episodes of agitation is more
      complex. In contrast to agitation associated with schizophrenia or bipolar mania,
      no agents have yet been approved by regulatory agencies for the treatment of
      persistent aggressive behavior. The strongest evidence supports the use of
      clozapine as an antihostility agent, followed by olanzapine. Adjunctive
      strategies with anticonvulsants and beta-adrenergic agents may also be worthwhile
      to consider. 

PMID- 24571829
TI  - Non-invasive measurement of brain temperature with microwave radiometry:
      demonstration in a head phantom and clinical case.
AB  - This study characterizes the sensitivity and accuracy of a non-invasive microwave
      radiometric thermometer intended for monitoring body core temperature directly in
      brain to assist rapid recovery from hypothermia such as occurs during surgical
      procedures. To study this approach, a human head model was constructed with
      separate brain and scalp regions consisting of tissue equivalent liquids
      circulating at independent temperatures on either side of intact skull. This test
      setup provided differential surface/deep tissue temperatures for quantifying
      sensitivity to change in brain temperature independent of scalp and surrounding
      environment. A single band radiometer was calibrated and tested in a multilayer
      model of the human head with differential scalp and brain temperature. Following
      calibration of a 500MHz bandwidth microwave radiometer in the head model,
      feasibility of clinical monitoring was assessed in a pediatric patient during a 2
      hour surgery. The results of phantom testing showed that calculated radiometric
      equivalent brain temperature agreed within 0.4 degrees C of measured temperature
      when the brain phantom was lowered 10 degrees C and returned to original
      temperature (37 degrees C), while scalp was maintained constant over a 4.6-hour
      experiment. The intended clinical use of this system was demonstrated by
      monitoring brain temperature during surgery of a pediatric patient. Over the 2
      hour surgery, the radiometrically measured brain temperature tracked within 1-2
      degrees C of rectal and nasopharynx temperatures, except during rapid cooldown
      and heatup periods when brain temperature deviated 2-4 degrees C from slower
      responding core temperature surrogates. In summary, the radiometer demonstrated
      long term stability, accuracy and sensitivity sufficient for clinical monitoring
      of deep brain temperature during surgery. 

PMID- 24571830
TI  - Differential diagnosis of neurodegenerative dementias using metabolic phenotypes
      on F-18 FDG PET/CT.
AB  - Positron emission tomography (PET) imaging with F-18 fluorodeoxyglucose (FDG) can
      be used as a downstream marker of neuronal injury, a hallmark of
      neurodegenerative dementias. Characteristic patterns of regional glucose
      metabolism have been used to classify the dementia subtypes, namely Alzheimer's
      dementia (AD), frontotemporal dementia (FTD), diffuse Lewy body (DLBD) and
      vascular dementia (VD). We undertook this study to assess the utility of FDG-PET
      in the differential diagnosis of dementia subtypes. One hundred and twenty-five
      patients diagnosed with dementia were referred from cognitive disorders and
      memory clinics of speciality neurology centres for the FDG-PET study. Imaging
      based diagnosis of dementia type was established in 101 patients by visual
      assessment of individual scans by a PET physician blinded to the clinical
      diagnosis. The results were compared with an 18-month follow-up clinical
      assessment made by the specialist neurologist. Concordance of visual evaluation
      of FDG-PET scans with clinical diagnosis of the dementia type was achieved in 90%
      of patients scanned. This concordance was 93.4% for AD, 88.8% for FTD, 66.6% for
      DLBD and 92.3% for the other dementia syndromes. FDG-PET performed after the
      initial work-up of dementias is useful for supporting the clinical diagnosis of
      dementia subtype. 

PMID- 24571831
TI  - Ivy sign in mildly symptomatic beta-thalassemia intermedia, with development of
      moyamoya disease.
AB  - Cerebrovascular occlusive disease with secondary proliferative angiogenesis can
      be idiopathic as a standalone disease state, known as moyamoya disease, or it may
      develop secondary to different disease entities, such as chronic
      hemoglobinopathies, in which case it is known as moyamoya syndrome. Although
      moyamoya syndrome has been well described with sickle cell anemia, its
      association with other hemoglobinopathies is rarely reported. We describe a 16
      year-old girl with beta-thalassemia intermedia who presented with recurrent
      headaches and focal seizures non-responsive to medical treatment. Magnetic
      resonance imaging showed diffuse intrasulcal bright signal intensity on fluid
      attenuated inversion recovery and leptomeningeal enhancement previously termed
      the "ivy sign", and her magnetic resonance angiography was consistent with
      bilateral moyamoya disease. The literature describing and explaining the
      pathogenesis of the "ivy sign" and its relationship to moyamoya disease was
      reviewed. 

PMID- 24571832
TI  - MR anatomy of deep brain nuclei with special reference to specific diseases and
      deep brain stimulation localization.
AB  - Diseases affecting the basal ganglia and deep brain structures vary widely in
      etiology and include metabolic, infectious, ischemic, and neurodegenerative
      conditions. Some neurologic diseases, such as Wernicke encephalopathy or
      pseudohypoparathyroidism, require specific treatments, which if unrecognized
      could lead to further complications. Other pathologies, such as hypertrophic
      olivary degeneration, if not properly diagnosed may be mistaken for a primary
      medullary neoplasm and create unnecessary concern. The deep brain structures are
      complex and can be difficult to distinguish on routine imaging. It is imperative
      that radiologists first understand the intrinsic anatomic relationships between
      the different basal ganglia nuclei and deep brain structures with magnetic
      resonance (MR) imaging. It is important to understand the "normal" MR signal
      characteristics, locations, and appearances of these structures. This is
      essential to recognizing diseases affecting the basal ganglia and deep brain
      structures, especially since most of these diseases result in symmetrical, and
      therefore less noticeable, abnormalities. It is also crucial that neurosurgeons
      correctly identify the deep brain nuclei presurgically for positioning deep brain
      stimulator leads, the most important being the subthalamic nucleus for Parkinson
      syndromes and the thalamic ventral intermediate nucleus for essential tremor.
      Radiologists will be able to better assist clinicians in diagnosis and treatment
      once they are able to accurately localize specific deep brain structures. 

PMID- 24571833
TI  - EEG-fMRI evaluation of patients with mesial temporal lobe sclerosis.
AB  - This preliminary study sought more information on blood oxygen level dependent
      (BOLD) activation, especially contralateral temporal/extratemporal spread, during
      continuous EEG-fMRI recordings in four patients with mesial temporal sclerosis
      (MTS). In two patients, EEG showed unilateral focal activity during the EEG-fMRI
      session concordant with the interictal focus previously identified with standard
      and video-poly EEG. In the other two patients EEG demonstrated a contralateral
      diffusion of the irritative focus. In the third patient (with the most drug
      resistant form and also extratemporal clinical signs), there was an extratemporal
      diffusion over frontal regions, ipsilateral to the irritative focus. fMRI
      analysis confirmed a single activation in the mesial temporal region in two
      patients whose EEG showed unilateral focal activity, while it demonstrated a
      bilateral activation in the mesial temporal regions in the other two patients. In
      the third patient, fMRI demonstrated an activation in the supplementary motxor
      area. This study confirms the most significant activation with a high firing rate
      of the irritative focus, but also suggests the importance of using new techniques
      (such as EEG-fMRI to examine cerebral blood flow) to identify the controlateral
      limbic activation, and any other extratemporal activations, possible causes of
      drug resistance in MTS that may require a more precise pre-surgical evaluation
      with invasive techniques. 

PMID- 24571834
TI  - Brain herniations into the dural venous sinuses or calvarium: MRI of a recently
      recognized entity.
AB  - Brain herniations into dural venous sinuses (DVS) are rare findings recently
      described and their etiology and clinical significance are controversial. We
      describe five patients with brain herniations into the DVS or calvarium
      identified on MRI, and discuss their imaging findings, possible causes, and
      relationship to the patient's symptoms. All patients were examined with MRI
      including high resolution pre- and post-contrast T1- and T2-weighted sequences.
      With respect to brain herniations we documented their locations, signal
      intensities in different sequences, and size. We then reviewed clinical records
      in an attempt to establish if any symptoms were related to the presence of these
      herniations. Three males and two females were examined (age range, 11-68 years).
      Three patients had unilateral temporal lobe herniations into transverse sinuses,
      one had a cerebellar herniation into the skull, and one had bilateral temporal
      lobe herniations into the transverse sinuses as well as a cerebellar herniation
      into the sigmoid sinus. In all, the herniated brain and surrounding cerebrospinal
      fluid (CSF) had normal signal intensity on all MRI sequences. When correlated
      with clinical symptoms, brain herniations were thought to be incidental and
      asymptomatic in three patients and two patients had histories of headaches. Brain
      herniations with surrounding CSF into the DVS/skull should be considered
      potential sources of filling defects in the DVS. We believe that they are
      probably incidental findings that may be more common than previously recognized
      and should be not confused with the more common arachnoid granulations, clots, or
      tumors. Two patients had headaches, but their relation to the presence of
      herniated brain was uncertain. 

PMID- 24571836
TI  - Diffusion tensor tractography in the presurgical assessment of cerebral gliomas.
AB  - Glioma is the most common intra-axial brain tumor characterized by invasion into
      the surrounding white matter (WM) tracts. These tumors are usually diagnosed by
      conventional MRI, but this method is unable to describe the relationship between
      tumor and neighboring WM tracts. Diffusion tensor tractography (DTT) is a new
      imaging modality which can solve this problem. The current study evaluated the
      application of DTT imaging in the presurgical assessment of gliomas, and
      introduces this new modality and its importance to physicians and imaging centers
      in Iran. Ten patients with intra-axial brain tumor and suspicion of glioma
      underwent conventional brain MRI pulse sequences and DTT imaging between December
      2011 and February 2013 with a 1.5 Tesla system using 64 independent diffusion
      encoding directions. Acquired images were assessed by the neuroradiologist and
      neurosurgeon. The treatment strategies were recognized and compared using data
      before and after the tractography. On the basis of DTT data, the treatment
      strategy changed from radiotherapy to the craniotomy in seven patients, and in
      one patient, the neurosurgeon preferred to avoid surgery. In one patient, the
      treatment technique did not change, and in the last one radiosurgery was replaced
      by craniotomy. As we can infer from this study, based on the tractography
      results, the treatment strategy may be changed, and the treatment technique could
      be devised more accurately and may lead to fewer postoperative neurological
      deficits and better outcomes. 

PMID- 24571835
TI  - Evaluation of apparent diffusion coefficient thresholds for diagnosis of
      medulloblastoma using diffusion-weighted imaging.
AB  - We assess a diffusion-weighted imaging (DWI) analysis technique as a potential
      basis for computer-aided diagnosis (CAD) of pediatric posterior fossa tumors. A
      retrospective medical record search identified 103 children (mean age: 87 months)
      with posterior fossa tumors having a total of 126 preoperative MR scans with DWI.
      The minimum ADC (ADCmin) and normalized ADC (nADC) values [ratio of ADCmin values
      in tumor compared to normal tissue] were measured by a single observer blinded to
      diagnosis. Receiver operating characteristic (ROC) curves were generated to
      determine the optimal threshold for which the nADC and ADCmin values would
      predict tumor histology. Inter-rater reliability for predicting tumor type was
      evaluated using values measured by two additional observers. At histology, ten
      tumor types were identified, with astrocytoma (n=50), medulloblastoma (n=33), and
      ependymoma (n=9) accounting for 89%. Mean ADCmin (0.54 * 10(-3) mm(2)/s) and nADC
      (0.70) were lowest for medulloblastoma. Mean ADCmin (1.28 * 10(-3) mm(2)/s) and
      nADC (1.64) were highest for astrocytoma. For the ROC analysis, the area under
      the curve when discriminating medulloblastoma from other tumors using nADC was
      0.939 and 0.965 when using ADCmin. The optimal ADCmin threshold was 0.66 * 10(-3)
      mm(2)/s, which yielded an 86% positive predictive value, 97% negative predictive
      value, and 93% accuracy. Inter-observer variability was very low, with near
      perfect agreement among all observers in predicting medulloblastoma. Our data
      indicate that both ADCmin and nADC could serve as the basis for a CAD program to
      distinguish medulloblastoma from other posterior fossa tumors with a high degree
      of accuracy. 

PMID- 24571837
TI  - Acute ischemic stroke secondary to glioblastoma. A case report.
AB  - Glioblastoma is a malignant infiltrative glial tumor occurring most often over 50
      years of age, with diverse clinical presentations. We describe a case of temporal
      lobe glioblastoma with a rare presentation as an acute ischemic stroke,
      discussing the imaging and histopathological findings, and reviewing the
      literature. A 77-year-old woman had sudden onset of left hemiparesis and
      hemihypoesthesia. The neuroradiological studies revealed an acute ischemic lesion
      in the right lenticulostriate arteries territory and a right anterior temporal
      lobe tumor, enhancing heterogeneously after contrast with enhancement of the
      right middle cerebral artery wall. Histopathological analysis of the resected
      temporal lesion revealed a glioblastoma multiforme with tumoral infiltration of
      the vascular wall. Glioblastoma should be considered in the etiology of acute
      ischemic stroke, where neuroimaging plays an important diagnostic role, enabling
      a more immediate therapeutic approach, with a consequent impact on survival. 

PMID- 24571838
TI  - Reliability of CT perfusion in the evaluation of the ischaemic penumbra.
AB  - CT perfusion (CTP) is part of the initial evaluation of stroke patients, allowing
      differentiation between infarcted tissue and the ischaemic penumbra and helping
      in the selection of patients for endovascular treatment. This study assessed the
      reliability of the qualitative evaluation CTP maps in defining the ischemic
      penumbra and identified potential pitfalls associated with this technique. We
      reviewed CTP scans of 45 consecutive patients admitted to our institution with
      anterior circulation acute ischaemic stroke. Two neuroradiologists performed
      qualitative evaluations of cerebral blood volume (CBV) and mean transit time
      (MTT) maps, using 24h follow-up non-contrast CT as surrogate marker for the area
      of definitive infarct. For each slice analyzed, the area of qualitative
      alteration in the CBV and MTT maps was classified as either being inferior, equal
      or superior to the area of infarct on the follow-up CT. Three out of 45 (7%)
      patients had admission CT CBV abnormalities larger than follow-up lesions; 34/45
      (76%) patients had infarct areas smaller than initial MTT prolongation. In the
      group of patients with no recanalization 12/19 (63%) had infarct areas smaller
      than initial MTT lesion. CBV abnormality is a reliable marker for an irreversible
      ischaemic lesion, although rarely it may overestimate the ischaemic "core",
      possibly due to delay in contrast arrival to the brain. In the majority of
      patients without recanalization, MTT overestimated final infarct areas, probably
      because it does not differentiate true "at risk" penumbra from benign oligaemia.
      Qualitative evaluation of CBV and MTT maps may overestimate the real ischaemic
      penumbra. 

PMID- 24571839
TI  - Recurrent temporal bone tenosynovial giant cell tumor with chondroid metaplasia:
      the use of imaging to assess recurrence.
AB  - Tenosynovial giant cell tumor (TGCT) is a benign proliferative lesion of unclear
      etiology. It is predominantly monoarticular and involves the synovium of the
      joint, tendon sheath, and bursa. TGCT of the temporomandibular joint (TMJ) is
      rare and aggressive resulting in destruction of surrounding structures. The
      diagnosis may be suggested by imaging, mainly by the MR features and PET/CT, and
      confirmed by histopathology. We describe the case of a 50-year-old man who
      presented with right-sided hearing loss, tinnitus and TMJ pain. Pathology
      revealed tenosynovial giant cell tumor with chondroid metaplasia. Six years later
      he developed a recurrence, which was documented to our knowledge for the first
      time with CT, MR and FDG PET/CT imaging. 

PMID- 24571840
TI  - Thromboembolic complication following neurointervention in ruptured anomalous
      hyperplastic anterior choroidal artery aneurysm.
AB  - The anterior choroidal artery (AchA) is an important cerebral artery despite its
      small diameter and relatively short course, because it provides blood supply to
      several important structures. Hyperplastic AchA is an extremely rare anomaly, and
      its clinical significance is the increased occurrence of intracranial aneurysm
      formation compared with an ordinary AchA. Because it has many small choroidal
      branches, subtle injury to the artery may result in severe complications. We
      describe a patient with a ruptured aneurysm in anomalous hyperplastic AchA, who
      developed an acute internal capsule infarction after coil embolization in spite
      of saving the parent artery. 

PMID- 24571841
TI  - Predictors of total obliteration in endovascular treatment of cerebral
      arteriovenous malformations.
AB  - Endovascular therapy is a therapeutic option that can achieve total obliteration
      of cerebral arteriovenous malformations (AVMs). The objective of this study was
      to determine the predictive factors of total obliteration in the endovascular
      treatment of AVMs. A prospective study was carried out in 71 patients with
      cerebral AVMs having undergone 147 embolization sessions with n-BCA, performed
      between 2006 and 2011. A univariate analysis was carried out, followed by a
      logistic regression analysis to determine the predictive factors of total
      obliteration. Total obliteration was achieved in 18.3% of the patients and
      angiographic control after 12 months showed the permanency of total occlusion in
      100% of the AVMs with initial total obliteration. Angiographic characteristics
      found favorable for total eradication were: AVM size under 3 cm and the presence
      of a single arterial pedicle. Predictive factors of total obliteration were an
      AVM diameter smaller than 3 cm (OR: 50.9; IC: 7.41 - 349, 0; P = 0.000), and
      opposing factors, a 3-6 cm diameter (OR: 11.7; IC: 2.49 - 55, 4; P = 0.002) and
      afferences of more than two vessels of the Willis polygon (OR: 7.0; IC: 1.12
      43.9; P = 0.038). An AVM diameter smaller than 3 cm is a predictive factor of
      total obliteration. Total postembolization obliteration persisted in 100% of the
      cases after 12 months. 

PMID- 24571842
TI  - Monitoring balloon test occlusion of the internal carotid artery with
      transcranial Doppler. A case report and literature review.
AB  - Angiographic balloon test occlusion (BTO) allows preoperative risk evaluation of
      patients undergoing permanent therapeutic occlusion of the internal carotid
      artery (ICA). The sensitivity of the BTO can be increased using different
      complementary techniques. Transcranial Doppler (TCD) stands out as a non
      invasive, bedside method providing real-time monitoring of cerebral
      haemodynamics, therefore accurately identifying patients at risk of stroke. A
      case of a 30-year-old woman with a giant intracavernous aneurysm of the left ICA
      presenting with subacute left VI nerve palsy is described. A pre-operative TCD-
      and EEG-monitored BTO of the left ICA was performed. The 16.7% drop found in the
      middle cerebral artery's peak systolic velocity (PSVMCA) predicts clinical and
      haemodynamic tolerance to the permanent loss of that vessel. This case
      illustrates the potential of TCD monitoring during temporary BTO of the ICA. It
      highlights its ability to provide a complete preclinical evaluation of
      collateralization and autoregulatory adaptation to unilateral ICA occlusion. TCD
      may also decrease the time of occlusion required for the BTO. 

PMID- 24571843
TI  - Target volume delineation in breast conserving radiotherapy: are co-registered CT
      and MR images of added value?
AB  - INTRODUCTION: In breast conserving radiotherapy differences of target volume
      delineations between observers do occur. We evaluated whether delineations based
      on co-registered computed tomography (CT) and magnetic resonance (MR) imaging may
      result in an improved consistency between observers. We used the delineation
      conformity index (CI) to compare clinical target volumes of glandular breast
      tissue (CTV breast) and lumpectomy cavity (LC) on both imaging modalities.
      METHODS AND MATERIALS: Four observers delineated CTV breast and LC on co
      registered CTMR images in ten breast cancer patients. CIs were determined for CT
      and CTMR. Furthermore, the Cavity Visualization Score (CVS) of LC was taken into
      account. RESULTS: The mean CI for CTV breast (CICT;CTV: 0.82 and CICT-CTMR;CTV:
      0.80) and LC (CICT;LC: 0.52 and CICT-CTMR;LC: 0.48) did not differ significantly
      (p=0.07 and p=0.33, respectively). Taking CVS into account for the LC, with a CVS
      >= 4 the mean CI was 0.62 for both CICT;LC and CICT-CTMR;LC. CONCLUSION: The mean
      volume of the delineated glandular breast tissue based on CT was significantly
      larger compared to the volume based on CTMR. For patients with a CVS >= 4, the
      mean CIs of the LC were higher compared to CVS<4 for volumes delineated on both
      CT as well as CTMR images. In our study cohort no significant differences between
      the CIs of the CTV breast and the LC delineated on CTMR co-registered images were
      found compared to the CIs on CT images only. Adding MR images does not seem to
      improve consistency of the delineation of the CTV breast and the LC, even though
      the volumes were copied from CT images. Since we included only ten patients,
      caution should be taken with regard to the results of our study.

PMID- 24571844
TI  - [ Low-threshold support services for people with dementia from the family carers'
      viewpoint].
AB  - Low-threshold support services are one possibility to relieve family carers with
      an hourly care for people with dementia. The aim of the study is to invest
      aspects of low-thresholdness (accessibility, flexibility, reachability,
      cheapness) with regards to content and to organisation. In an explorative cross
      sectional study we collected the estimation according to low-threshold support
      services of family carers of people with dementia using those services in two
      regions of North-Rhine-Westphalia (Germany). The analysis was descriptive. The
      results show, that the 53 family carers estimate the aspects with regards to
      content mainly with focus on the well-being of the people with dementia as
      crucial, meanwhile the organisational aspects and the low-thresholdness were less
      important. Carers' burden was no object. For the family carers and the decision
      to utilise a low-threshold support service it seems to be import to have a
      transparent description of the care with a focus on the needs and well-being of
      the person with dementia. 

PMID- 24571845
TI  - [Interrater reliability and agreement of the Swiss MDS version 2.0].
AB  - Numerous studies have been performed to assess the validity and reliability of
      the Minimum Data Set (MDS) of the Resident Assessment Instrument (RAI), which was
      developed and initially implemented in the United States. In general, RAI-MDS 2.0
      has been reported to have moderate to high interrater reliability. From the late
      1990s onwards the geriatric nursing assessment has been used in nursing homes in
      Switzerland. The objective of this study was to examine interrater agreement and
      reliability of the Swiss version of RAI-MDS 2.0 for the first time. For this
      purpose, 61 nursing home residents were independently assessed by two assessors.
      The MDS coordinator of the nursing home and an extern expert conducted
      independent resident assessments by reviewing the chart and asking front line
      staff about the residents' behaviour. Proportions of exact agreement were
      calculated and interrater reliability was assessed using kappa and intraclass
      correlation (ICC) coefficients. For most of the checked items, a high agreement
      between the two raters was observed. The reliability coefficients for 47 % of the
      items reached values between 0,81 and 1,0. 29 % of the items achieved values
      between 0,61 and 0,80. The values of 10 % of the items ranged between 0,41 and
      0,60. Two items assessing skin condition obtained a value of 0,25 and 0,
      respectively. The results of the reliability analysis show that mainly items
      evaluating pain, mood and behavior, and some items estimating physical function
      and skin condition are less reliable. 

PMID- 24571846
TI  - [ Comparison of BESA and RAI: evaluating the outcomes of two assessment
      instruments for long-term residential care needs].
AB  - In Switzerland, the level of nursing care required for residents in nursing homes
      is either assessed by the BESA Catalogue 2010 or by the Minimum Data Set (MDS) of
      the Resident Assessment Instrument (RAI). Within both instruments the nursing
      care need is represented in minutes. According to these minutes, the resident is
      allocated to a tariff level. The aim of the study was to compare the outcomes of
      the two assessment instruments BESA Catalogue 2010 and MDS. For this purpose data
      were collected in two nursing homes. At each facility 60 nursing home residents
      were assessed with the BESA Catalogue 2010 and the MDS. The assessments were
      independently performed by nurses of the facility (internal assessment) and by
      system experts (external assessment). Descriptive data analysis and a comparison
      of the outcome in minutes and with regard to tariff level were carried out. In
      average, internal assessments were higher than external assessments. In both
      nursing homes, half or 54 % of residents were allocated into a higher tariff
      level by means of internal assessment. Comparing the outcomes in total and within
      tariff level, significant differences were found. Different classifications may
      occur, especially for residents with high nursing care needs. As a result, higher
      or lower costs of nursing care may arise.

PMID- 24571847
TI  - [Comparative quality measurements part 3: funnel plots].
AB  - Comparative quality measurements between organisations or institutions are
      common. Quality measures need to be standardised and risk adjusted. Random error
      must also be taken adequately into account. Rankings without consideration of the
      precision lead to flawed interpretations and enhances "gaming". Application of
      confidence intervals is one possibility to take chance variation into account.
      Funnel plots are modified control charts based on Statistical Process Control
      (SPC) theory. The quality measures are plotted against their sample size. Warning
      and control limits that are 2 or 3 standard deviations from the center line are
      added. With increasing group size the precision increases and so the control
      limits are forming a funnel. Data points within the control limits are considered
      to show common cause variation; data points outside special cause variation
      without the focus of spurious rankings. Funnel plots offer data based information
      about how to evaluate institutional performance within quality management
      contexts. 

PMID- 24571848
TI  - [The implementation of the national expert standard for pain management in
      nursing from the viewpoint of the registered nurses: a comparative evaluation
      studies in nursing homes for the aged in Baden-Wurttemberg].

PMID- 24571855
TI  - Tactile acuity training for patients with chronic low back pain: a pilot
      randomised controlled trial.
AB  - BACKGROUND: Chronic pain can disrupt the cortical representation of a painful
      body part. This disruption may play a role in maintaining the individual's pain.
      Tactile acuity training has been used to normalise cortical representation and
      reduce pain in certain pain conditions. However, there is little evidence for the
      effectiveness of this intervention for chronic low back pain (CLBP). The primary
      aim of this study was to inform the development of a fully powered randomised
      controlled trial (RCT) by providing preliminary data on the effect of tactile
      acuity training on pain and function in individuals with CLBP. The secondary aim
      was to obtain qualitative feedback about the intervention. METHODS: In this mixed
      methods pilot RCT 15 individuals were randomised to either an intervention
      (tactile acuity training) or a placebo group (sham tactile acuity training). All
      participants received 3 sessions of acuity training (intervention or sham) from a
      physiotherapist and were requested to undertake daily acuity home training
      facilitated by an informal carer (friend/relative). All participants also
      received usual care physiotherapy. The primary outcome measures were pain (0
      100visual analogue scale (VAS)) and function (Roland Morris Disability
      Questionnaire (RMDQ)). Participants and their informal carers were invited to a
      focus group to provide feedback on the intervention. RESULTS: The placebo group
      improved by the greatest magnitude for both outcome measures, but there was no
      statistically significant difference (Mean difference (95%CI), p-value) between
      groups for change in pain (25.6 (-0.7 to 51.9), p = 0.056) or function (2.2 (-1.6
      to 6.0), p = 0.237). Comparing the number of individuals achieving a minimally
      clinically significant improvement, the placebo group had better outcomes for
      pain with all participants achieving >=30% improvement compared to only a third
      of the intervention group (6/6 vs. 3/9, p = 0.036). Qualitatively, participants
      reported that needing an informal carer was a considerable barrier to the home
      training component of the study. CONCLUSIONS: This pilot RCT found tactile acuity
      training to be no more effective than sham tactile acuity training for function
      and less effective for pain in individuals with CLBP. That the intervention could
      not be self-applied was a considerable barrier to its use. TRIAL REGISTRATION
      ISRCTN: ISRCTN98118082.

PMID- 24571857
TI  - An evidence-based framework to measure quality of allied health care.
AB  - BACKGROUND: There is no standard way of describing the complexities of allied
      health (AH) care, or its quality. AH is an umbrella term which excludes medicine
      and nursing, and variably includes disciplines which provide therapy, diagnostic,
      or scientific services. This paper outlines a framework for a standard approach
      to evaluate the quality of AH therapy services. METHODS: A realist synthesis
      framework describing what AH does, how it does it, and what is achieved, was
      developed. This was populated by the findings of a systematic review of
      literature published since 1980 reporting concepts of quality relevant to AH.
      Articles were included on quality measurement concepts, theories, debates, and/or
      hypothetical frameworks. RESULTS: Of 139 included articles, 21 reported on
      descriptions of quality potentially relevant to AH. From these, 24 measures of
      quality were identified, with 15 potentially relating to what AH does, 17 to how
      AH delivers care, 8 relating to short term functional outcomes, and 9 relating to
      longer term functional and health system outcomes. CONCLUSIONS: A novel evidence
      based quality framework was proposed to address the complexity of AH therapies.
      This should assist in better evaluation of AH processes and outcomes, costs, and
      evidence-based engagement of AH providers in healthcare teams.

PMID- 24571858
TI  - Red blood cell transfusion in septic shock - clinical characteristics and outcome
      of unselected patients in a prospective, multicentre cohort.
AB  - BACKGROUND: Treating anaemia with red blood cell (RBC) transfusion is frequent,
      but controversial, in patients with septic shock. Therefore we assessed
      characteristics and outcome associated with RBC transfusion in this group of high
      risk patients. METHODS: We did a prospective cohort study at 7 general intensive
      care units (ICUs) including all adult patients with septic shock in a 5-month
      period. RESULTS: Ninety-five of the 213 included patients (45%) received median 3
      (interquartile range 2-5) RBC units during shock. The median pre-transfusion
      haemoglobin level was 8.1 (7.4-8.9) g/dl and independent of shock day and
      bleeding. Patients with cardiovascular disease were transfused at higher
      haemoglobin levels. Transfused patients had higher Simplified Acute Physiology
      Score (SAPS) II (56 (45-69) vs. 48 (37-61), p = 0.0005), more bleeding episodes,
      lower haemoglobin levels days 1 to 5, higher Sepsis-related Organ Failure
      Assessment (SOFA) scores (days 1 and 5), more days in shock (5 (3-10) vs. 2 (2
      4), p = 0.0001), more days in ICU (10 (4-19) vs. 4 (2-8), p = 0.0001) and higher
      90-day mortality (66 vs. 43%, p = 0.001). The latter association was lost after
      adjustment for admission category and SAPS II and SOFA-score on day 1.
      CONCLUSIONS: The decision to transfuse patients with septic shock was likely
      affected by disease severity and bleeding, but haemoglobin level was the only
      measure that consistently differed between transfused and non-transfused
      patients.

PMID- 24571860
TI  - 'Why nurses are leaving the profession ... lack of support from managers': What
      nurses from an e-cohort study said.
AB  - The shortage of nurses is known. We explored nurses' reasons for leaving the
      profession based on responses from an e-newsletter of the Nurses and Midwives e
      cohort Study. Qualitative content analysis of data from email responses (n = 66)
      showed 'Lack of support' as a social work value describing their manager's lack
      of support, unsupportive relationships within their work group, and a health-care
      system putting business principles before care resulting in job dissatisfaction
      and nurse turnover. These findings are examples of a 'complex'/'wicked' problem
      and as such will resist simple solutions to the presenting issues. The dialogic
      process such as Open Space Technology and Talking Circles should be considered as
      potentially suitable to the needs of nurses. 

PMID- 24571856
TI  - Endocannabinoids in synaptic plasticity and neuroprotection.
AB  - Endocannabinoids (eCBs) are endogenous lipid mediators involved in a variety of
      physiological, pharmacological, and pathological processes. While activation of
      the eCB system primarily induces inhibitory effects on both GABAergic and
      glutamatergic synaptic transmission and plasticity through acting on
      presynaptically expressed CB1 receptors in the brain, accumulated information
      suggests that eCB signaling is also capable of facilitating or potentiating
      excitatory synaptic transmission in the hippocampus. Recent studies show that a
      long-lasting potentiation of excitatory synaptic transmission at Schaffer
      collateral (SC)-CA1 synapses is induced by spatiotemporally primed inputs,
      accompanying with a long-term depression of inhibitory synaptic transmission (I
      LTD) in hippocampal CA1 pyramidal neurons. This input timing-dependent long
      lasting synaptic potentiation at SC-CA1 synapses is mediated by 2
      arachidonoylglycerol (2-AG) signaling triggered by activation of postsynaptic N
      methyl-D-aspartate receptors, group I metabotropic glutamate receptors (mGluRs),
      and a concurrent rise in intracellular Ca(2+). Emerging evidence now also
      indicates that 2-AG is an important signaling mediator keeping brain homeostasis
      by exerting its anti-inflammatory and neuroprotective effects in response to
      harmful insults through CB1/2 receptor-dependent and/or -independent mechanisms.
      Activation of the nuclear receptor protein peroxisome proliferator-activated
      receptor-gamma apparently is one of the important mechanisms in resolving
      neuroinflammation and protecting neurons produced by 2-AG signaling. Thus, the
      information summarized in this review suggests that the role of eCB signaling in
      maintaining integrity of brain function is greater than what we thought
      previously.

PMID- 24571859
TI  - Flavone-based ESIPT ratiometric chemodosimeter for detection of cysteine in
      living cells.
AB  - We have designed and synthesized a novel ratiometric fluorescent chemodosimeter
      MHF-based ESIPT process for specific detection of cysteine among the biological
      thiols. The probe MHF shows very weak blue fluorescence under UV excitation. Upon
      addition of cysteine (Cys), the reaction of Cys with MHF induces acrylate
      hydrolysis, thereby enabling the ESIPT process to shift the weak blue emission to
      a strong green emission with about 20-fold enhancement. We utilized (1)H NMR
      spectra to elucidate the fluorescence sensing mechanism. Moreover, the cellular
      imaging experiment indicated the MHF possessed excellent selectivity, low
      cytotoxicity, and desirable cell permeability for biological applications. 

PMID- 24571862
TI  - A novel nanoscale-dispersed eye ointment for the treatment of dry eye disease.
AB  - A novel nanoscale-dispersed eye ointment (NDEO) for the treatment of severe
      evaporative dry eye has been successfully developed. The excipients used as
      semisolid lipids were petrolatum and lanolin, as used in conventional eye
      ointment, which were coupled with medium-chain triglycerides (MCT) as a liquid
      lipid; both phases were then dispersed in polyvinyl pyrrolidone solution to form
      a nanodispersion. Single-factor experiments were conducted to optimize the
      formulations. A transmission electron micrograph showed that the ointment matrix
      was entrapped in the nanoemulsion of MCT, with a mean particle size of about 100
      nm. The optimized formulation of NDEO was stable when stored for six months at 4 
      degrees C, and demonstrated no cytotoxicity to human corneal epithelial cells
      when compared with commercial polymer-based artificial tears (Tears Natural
      Forte). The therapeutic effects of NDEO were evaluated on a mouse model with 'dry
      eye'. Both the tear break-up time and fluorescein staining demonstrated
      therapeutic improvement, displaying a trend of positive correlation with higher
      concentrations of ointment matrix in the NDEO formulations compared to a marketed
      product. Histological evaluation demonstrated that the NDEO restored the normal
      corneal and conjunctival morphology and is safe for ophthalmic application.

PMID- 24571861
TI  - Identification of the variations in the CPT1B and CHKB genes along with the HLA
      DQB1*06:02 allele in Turkish narcolepsy patients and healthy persons.
AB  - BACKGROUND: The HLA-DQB1*06:02 allele across all ethnic groups and the rs5770917
      variation between CPT1B and CHKB genes in Japanese and Koreans are common genetic
      susceptibility factors for narcolepsy. This comprehensive genetic study sought to
      assess variations in CHKB and CPT1B susceptibility genes and HLA-DQB1*06:02
      allele status in Turkish patients with narcolepsy and healthy persons. METHODS:
      CHKB/CPT1B genes were sequenced in patients with narcolepsy (n=37) and healthy
      persons (n=100) to detect variations. The HLA-DQB1*06:02 allele status was
      determined by sequence specific polymerase chain reaction. RESULTS: The HLA
      DQB1*06:02 allele was significantly more frequent in narcoleptic patients than in
      healthy persons (p=2*10(-7)) and in patients with narcolepsy and cataplexy than
      in those without (p=0.018). The mean of the multiple sleep latency test, sleep
      onset rapid eye movement periods, and frequency of sleep paralysis significantly
      differed in the HLA-DQB1*06:02-positive patients. rs5770917, rs5770911,
      rs2269381, and rs2269382 were detected together as a haplotype in three patients
      and 11 healthy persons. In addition to this haplotype, the indel variation
      (rs144647670) was detected in the 5' upstream region of the human CHKB gene in
      the patients and healthy persons carrying four variants together. CONCLUSION:
      This study identified a novel haplotype consisting of the indel variation, which
      had not been detected in previous studies in Japanese and Korean populations, and
      observed four single-nucleotide polymorphisms in CHKB/CPT1B. The study confirmed
      the association of the HLA-DQB1*06:02 allele with narcolepsy and cataplexy
      susceptibility. The findings suggest that the presence of HLA-DQB1*06:02 may be a
      predictor of cataplexy in narcoleptic patients and could therefore be used as an
      additional diagnostic marker alongside hypocretin.

PMID- 24571864
TI  - Lyme disease: neurology, neurobiology, and behavior.
AB  - The Lyme disease controversy can be largely linked to the misconception that
      neurobehavioral effects of illness constitute evidence of nervous system
      infection. Appropriate differentiation between neuroborreliosis (nervous system
      Borrelia burgdorferi infection) and Lyme encephalopathy (altered nervous system
      function in individuals with systemic but not nervous system infection)-or
      encephalopathies of other etiologies-would lessen the controversy considerably,
      as the attribution of nonspecific symptoms to supposed ongoing central nervous
      system infection is a major factor perpetuating the debate. Epidemiologic
      considerations suggest that the entities referred to as "posttreatment Lyme
      disease" and "chronic Lyme disease" may not actually exist but rather reflect
      anchoring bias, linking common, nonspecific symptoms to an antecedent medical
      event. On the other hand, there are data suggesting possible mechanisms by which
      posttreatment Lyme disease could occur.

PMID- 24571865
TI  - Pro-resolution of inflammation: a potential strategy for treatment of acute lung
      injury/acute respiratory distress syndrome.

PMID- 24571863
TI  - Hepatitis B testing and vaccination among adults with sexually transmitted
      infections in a large managed care organization.
AB  - Data on viral hepatitis B (HBV) testing and vaccination in primary care settings
      among persons at sexual risk for HBV infection have been sparse. We examined
      rates and factors associated with HBV serologic testing and vaccination rates in
      adults infected with sexually transmitted infections. We conducted a
      retrospective cohort study of adults diagnosed with chlamydia, gonorrhea, or
      syphilis in Kaiser Permanente Southern California in 2008-2011. The vaccine
      series initiation was examined in subjects who were tested susceptible. The 90
      day hepatitis B surface antigen (HBsAg) testing rate was 28.1% in 15 357 adults.
      Testing rates increased through the study period. Only 8.8% of patients received
      both HBsAg and hepatitis B surface antibody tests to determine prior exposure and
      susceptibility to HBV. Among those who were tested susceptible, 116 (10.6%)
      subjects initiated the vaccine series. In multivariable logistic regression
      analysis, the odds of receiving testing was inversely associated with female sex,
      black race, other/unknown race, or having prespecified chronic comorbidities. In
      survival analysis, adults aged 25-34 years and >=55 years were more likely to
      initiate hepatitis B vaccine series compared with those aged 18-24 years. There
      are missed opportunities in HBV testing and vaccination in primary care.
      Implementation of provider decision-making support tools in the electronic
      medical record system may potentially improve hepatitis B testing and vaccination
      rates.

PMID- 24571866
TI  - Effects of resolvin D1 on inflammatory responses and oxidative stress of
      lipopolysaccharide-induced acute lung injury in mice.
AB  - BACKGROUND: A variety of inflammatory mediators and effector cells participate
      together in acute lung injury, and lead to secondary injury that is due to an
      inflammatory cascade and secondary diffuse lung parenchyma injury. Inflammation
      is associated with an oxidative stress reaction, which is produced in the
      development of airway inflammation, and which has positive feedback on
      inflammation itself. Resolvin D1 can reduce the infiltration of neutrophils,
      regulate cytokine levels and reduce the inflammation reaction, and thereby
      promote the resolution of inflammation. The purpose of this study is to
      investigate the effects of resolvin D1 on an inflammatory response and oxidative
      stress during lipopolysaccharide (LPS)-induced acute lung injury. METHODS: LPS (3
      mg/kg) was used to induce the acute lung injury model. Pretreatment resolvin D1
      (100 ng/mouse) was given to mice 30 minutes before inducing acute lung injury.
      Mice were observed at 6 hours, 12 hours, 1 day, 2 days, 3 days, 4 days and 7 days
      after LPS was administrated, then they were humanely sacrificed. We collected
      bronchoalveolar lavage fluid (BALF) and the lung tissues for further analysis.
      Paraffin section and HE staining of the lung tissues were made for histopathology
      observations. Parts of the lung tissues were evaluated for wet-to-dry (W/D)
      weight ratio. tumor necrosis factor (TNF)-alpha, inter leukin (IL)-1beta, IL-10
      and myeloperoxidase (MPO) were detected by enzyme-linked immunosorbent assay
      (ELISA). A lipid peroxidation malondialdehyde (MDA) assay kit was used to detect
      MDA. A total superoxide dismutase assay kit with WST-1 was used to analyze
      superoxide dismutase (SOD). We determined the apoptosis of neutrophils by Flow
      Cytometry. A real-time quantitative PCR Detecting System detected the expression
      of mRNA for heme oxygenase (HO)-1. RESULTS: Pretreatment with resolvin D1 reduced
      the pathological damage in the lung, decreased the recruitment of neutrophils and
      stimulated their apoptosis. It markedly decreased the expressions of TNF-alpha,
      IL-1beta and increased the expressions of IL-10, and decreased the production of
      MDA and increased the expressions of SOD. The mRNA expression of HO-1 was also
      significantly increased. CONCLUSIONS: Resolvin D1 displays potent anti
      inflammatory actions by regulating cytokines, inhibiting aberrant neutrophil
      recruitment and stimulating apoptosis of neutrophils. Resolvin D1 can also
      relieve the injury due to oxidative stress. The mechanisms might be related to
      increase HO-1 expression.

PMID- 24571867
TI  - Protectin D1 promotes resolution of inflammation in a murine model of
      lipopolysaccharide-induced acute lung injury via enhancing neutrophil apoptosis.
AB  - BACKGROUND: Protectin D1 (PD1), derived from docosahexaenoic acid, has been shown
      to control and resolve inflammation in some experimental models of inflammatory
      disorders. We investigated the protective roles of protectin D1 in pulmonary
      inflammation and lung injury induced by lipopolysaccharide (LPS). METHODS: Mice
      were randomly assigned to six groups (n = 6 per group): sham-vehicle group, sham
      PD1 group, sham-zVAD-fmk group, LPS-vehicle group, LPS-PD1 group, and LPS-PD1
      zVAD-fmk group. Mice were injected intratracheally with 3 mg/kg LPS or saline,
      followed 24 hours later by intravenous injection of 200 ug/mouse PD1 or vehicle.
      At the same time, some mice were also injected intraperitoneally with the pan
      caspase inhibitor zVAD-fmk. Seventy-two hours after LPS challenge, samples of
      pulmonary tissue and bronchoalveolar lavage fluid were collected. Optical
      microscopy was used to examine pathological changes in lungs. Cellularity and
      protein concentration in bronchoalveolar lavage fluid were analyzed. Lung wet/dry
      ratios and myeloperoxidase activity were measured. Apoptosis of neutrophils in
      bronchoalveolar lavage fluid (BALF) was also evaluated by flow cytometry.
      RESULTS: Intratracheal instillation of LPS increased neutrophil counts, protein
      concentration in bronchoalveolar lavage fluid and myeloperoxidase activity, it
      induced lung histological injury and edema, and also suppressed apoptosis of
      neutrophils in BALF. Posttreatment with PD1 inhibited LPS-evoked changes in BALF
      neutrophil counts and protein concentration and lung myeloperoxidase activity,
      with the outcome of decreased pulmonary edema and histological injury. In
      addition, PD1 promoted apoptosis of neutrophils in BALF. The beneficial effects
      of PD1 were blocked by zVAD-fmk. CONCLUSION: Posttreatment with PD1 enhances
      resolution of lung inflammation during LPS-induced acute lung injury by enhancing
      apoptosis in emigrated neutrophils, which is, at least in part, caspase
      dependent.

PMID- 24571868
TI  - 15-deoxy-Delta12,14-prostaglandin J2 ameliorates endotoxin-induced acute lung
      injury in rats.
AB  - BACKGROUND: A proinflammatory milieu emerging in the lung due to neutrophil
      accumulation and activation is a key in the pathogenesis of acute lung injury
      (ALI). 15-deoxy-Delta(12, 14)-prostaglandin J2 (15d-PGJ2), one of the terminal
      products of the cyclooxygenase-2 pathway, is known to be the endogenous ligand of
      peroxisome proliferator-activated receptor gamma (PPAR-gamma) with multiple
      physiological properties. Growing evidence indicates that 15d-PGJ2 has anti
      inflammatory, antiproliferative, cytoprotective and pro-resolving effects. We
      investigated whether 15d-PGJ2 has a protective effect against endotoxin-induced
      acute lung injury in rats. METHODS: Twenty-four male Wistar rats were randomly
      assigned into four groups (n = 6 per group): sham+vehicle group, sham+15d-PGJ2
      group, LPS+vehicle group, and LPS+15d-PGJ2 group. The rats were given either
      lipopolysaccharide (LPS, 6 mg/kg intravenously) or saline, and pretreated with
      15d-PGJ2 (0.3 mg/kg intravenously) or its vehicle (dimethyl sulphoxide) 30
      minutes before LPS. Histological alterations, wet/dry weight (W/D) ratio and
      myeloperoxidase (MPO) activity as well as tumor necrosis factor (TNF)-alpha and
      cytokine-induced neutrophil chemoattractant-1 (CINC-1) levels were determined in
      lung tissues four hours after LPS injection. Immunohistochemical analysis for
      intercellular adhesion molecule-1 (ICAM-1) expression and Western blotting
      analysis for nuclear factor (NF)-kappaB p65 translocation and IkappaBalpha
      protein levels were also studied. RESULTS: 15d-PGJ2 pretreatment significantly
      attenuated LPS-induced lung injury, and reduced the increased W/D ratio, MPO
      activity, TNF-alpha, CINC-1 levels, and ICAM-1 expression in the lung. 15d-PGJ2
      also suppressed the nuclear NF-kappaB p65 translocation and increased cytosolic
      IkappaBalpha levels. CONCLUSIONS: 15d-PGJ2 protects against endotoxin-induced
      acute lung injury, most likely through the reduction of proinflammatory protein
      levels during endotoxemia subsequent to the inhibition of NF-kappaB activation.

PMID- 24571869
TI  - Impairment of recovery of muscle function by residual rocuronium after re
      transfusion of intraoperative salvaged blood.
AB  - BACKGROUND: Recurarization has previously been described in the context of acute
      normovolemic hemodilution. The aim of this study was to investigate the
      impairment of recovery of neuromuscular function after re-transfusion of
      intraoperative salvaged blood in patients treated with rocuronium. METHODS: We
      enrolled 50 patients undergoing general anesthesia for lumbar surgery.
      Intraoperative blood salvage (IBS) was used in 30 patients (group I); the
      remaining 20 comprised a control group (group C). Anesthesia was induced with
      fentanyl, midazolam, propofol and rocuronium. Rocuronium was infused to maintain
      neuromuscular blockade during surgery. Blood was collected from the operative
      field and re-transfused in the post-anesthesia care unit (PACU). Neuromuscular
      function was monitored using the train-of-four ratio (TOFr). Once the train-of
      four ratio exceeded 90 in the PACU, neuromuscular function was evaluated every 5
      minutes for 30 minutes. The TOFr and incremental recovery of TOFr from baseline
      were recorded. Salvaged blood was re-transfused at the beginning of the
      evaluation for patients in group I, and afterwards for patients in group C. Blood
      gas analysis was assessed before anesthesia and in the PACU. RESULTS: Incremental
      recovery of TOFr from baseline was significantly less in group I than controls at
      25 minutes (6.1 +/- 3.2 vs. 9.1 +/- 3.2, respectively; P = 0.001) and 30 minutes
      (7.1 +/- 3.2 vs. 10.0 +/- 2.2, respectively; P = 0.001). There were no
      significant differences in gas exchange between the groups. CONCLUSIONS: In
      patients who had received a rocuronium infusion during anesthesia, re-transfusion
      of salvaged blood significantly impaired recovery of neuromuscular function
      recovery in the PACU, but without significant impairment of respiratory function.

PMID- 24571870
TI  - Combined incisional ropivacaine infiltration and pulmonary recruitment manoeuvre
      for postoperative pain relief after diagnostic hysteroscopy and laparoscopy.
AB  - BACKGROUND: Preoperative incisional local anaesthesia with ropivacaine is a
      common method of providing post-laparoscopy pain relief. The pulmonary
      recruitment manoeuvre also provides pain relief, but the combined effect of these
      two methods on pain following laparoscopic procedures has not been reported. We
      investigated the efficacy of combining local anaesthetic infiltration of
      ropivacaine with pulmonary recruitment manoeuvre on postoperative pain following
      diagnostic hysteroscopy and laparoscopy. METHODS: This prospective, randomized,
      controlled study involved 60 patients divided into two groups (n = 30, each).
      Group 1 received 20 ml of 0.5% ropivacaine injected peri-incisionally
      preoperatively, with intra-abdominal carbon dioxide removed by passive deflation.
      Group 2 received 20 ml of 0.5% ropivacaine injected peri-incisionally with five
      manual inflations of the lungs with a positive-pressure ventilation of 40 cmH2O
      at the end of surgery. The last inflation was held for 5 seconds. The intensity
      of postoperative incisional and shoulder pain was evaluated using a numerical
      rating scale at 0, 2, 4, 8, 12, 24 and 48 hours postoperatively by an independent
      blinded anaesthesiologist. Tramadol was given postoperatively for analgesia.
      RESULTS: Compared with group 1, incisional ropivacaine infiltration combined with
      pulmonary recruitment manoeuvre significantly reduced dynamic pain at 0 hour, 4
      hours, and 24 hours postoperatively (4.1 +/- 2.2 vs. 2.1 +/- 1.9, P = 0.002; 2.7
      +/- 2.7 vs. 1.2 +/- 1.3, P = 0.035; and 3.5 +/- 2.1 vs. 2.1 +/- 1.8, P = 0.03,
      respectively). Static incisional pain was significantly relieved at 0 hour, 2
      hours, and 24 hours postoperatively (3.1 +/- 1.7 vs. 1.6 +/- 1.3, P = 0.001; 1.4
      +/- 1.3 vs. 0.5 +/- 0.8, P = 0.012; and 2.3 +/- 1.9 vs. 1.0 +/- 1.5, P = 0.038,
      respectively). Group 2 had more patients without shoulder pain (P < 0.05) and
      fewer requiring tramadol (P < 0.05). CONCLUSION: Ropivacaine with pulmonary
      recruitment manoeuvre provided simple and effective pain relief after diagnostic
      hysteroscopy and laparoscopy.

PMID- 24571871
TI  - Radial shock wave therapy in the treatment of chronic constriction injury model
      in rats: a preliminary study.
AB  - BACKGROUND: Pain physicians pay close attention to neuropathic pain (NP), since
      there is currently no ideal treatment. Radial shock wave therapy (RSWT) is a
      noninvasive treatment to chronic pain of soft tissue disorders. So far, there is
      no information on the use of RSWT for the treatment of NP. Therefore we observe
      the effects of RSWT on a NP model induced by chronic constriction injury (CCI) in
      rats. METHODS: Four different energy densities (1.0, 1.5, 2.0 and 2.5 bar) RSWT
      administered as a single session or repeated sessions in rats with NP induced by
      CCI of the sciatic nerve. The analgesic effect was assessed by measuring
      mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL). The
      safety was assessed through calculating sciatic functional index (SFI). RESULTS:
      MWT and TWL increased after a single session of RSWT from day 1 to day 5 but
      returned to baseline levels by day 10. Following repeated sessions of RSWT, both
      the MWT and TWL were significantly higher than NP group (P < 0.01) for at least 4
      weeks. In addition, no significant changes of SFI were observed in any groups
      after repeated sessions of RSWT and no increased pain or other side effects in
      any animals. CONCLUSIONS: A single session of RSWT is rapidly effective in the
      treatment of CCI, but the efficacy maintained in a short period. However,
      repeated sessions of RSWT have prolonged efficacy.

PMID- 24571872
TI  - Current attitudes toward organ donation after cardiac death in northwest China.
AB  - BACKGROUND: People's attitude toward organ donation after cardiac death (DCD) has
      not come to an agreement in different countries and regions. Influenced by the
      local culture in China for thousands of years, the general public has different
      ideas about this issue. The purpose of this study was to investigate the current
      attitudes trend and characteristics of transplantation with organs donated after
      cardiac death in northwest China. METHODS: This largest single-center cohort
      study was performed by an interview or by telephone using a questionnaire. The
      family members of potential DCD donors were recruited from the First Affiliated
      Hospital, medical college of Xi'an Jiaotong University located in a metropolitan
      area of northwest China. The 12-item attitude questionnaire was specifically
      developed from the literature review with coordinator, physician, and donor's
      family feedback. The participants were asked to rate the queries on a 5-point
      Likert intensity scale. RESULTS: The 174 participants included 56 (32.2%) women
      and 118 (67.8%) men. Most people were aged between 41 and 50 years (n = 63,
      36.2%), 31 and 40 years (n = 59, 33.9%), and less than 30 years (n = 36, 20.7%).
      The top five attitudes of participants were the best person to suggest organ
      donation to a family was ranked as the DCD coordinator of Red Cross Organization
      (RCO, n = 160, 92%), donor is a hero (n = 143, 82.2%), honor to be a donor's
      family member (n = 136, 78.2%), improved relationship with colleagues (n = 124,
      71.3%), and with recipient after donation (n = 123, 70.7%). The best person to
      suggest organ donation to a family was ranked as the coordinator of RCO (n = 160,
      92%), doctor unrelated to transplantation (n = 104, 59.8%), social worker (n =
      36, 20.7%), and doctor related to transplantation (n = 25, 14.4%). The top two
      reasons for non-consent to donation were that the family insisted on intact body
      after patient death and did not want to have surgery again (n = 51, 41.5%), and
      feared that they would be misunderstood by neighbors, relatives, and friends
      about donation (n = 28, 22.8%). CONCLUSIONS: This study revealed initial
      attitudes toward DCD in China. Some data afford insight into the decision-making
      procedure. The concerns of potential DCD donors and their families may help
      professionals provide better interventions in the future.

PMID- 24571873
TI  - Midterm results of diagnostic treatment and repair strategy in older patients
      presenting with nonrestrictive ventricular septal defect and severe pulmonary
      artery hypertension.
AB  - BACKGROUND: Congenital heart disease with severe pulmonary arterial hypertension
      (SPAH), previously thought to have irreversible pulmonary vascular disease (PVD),
      has been recently successfully corrected using diagnostic treatment and repair
      strategy by our surgery team. This study aimed to evaluate the midterm results of
      a selected cohort of older patients with nonrestrictive ventricular septal defect
      (VSD) and SPAH using diagnostic treatment and repair strategy. METHODS: The
      records of 56 patients older than six years with nonrestrictive VSD and SPAH
      undergoing diagnostic treatment and repair strategy from 2006 to 2012 were
      retrospectively reviewed. All patients received advanced pulmonary arterial
      hypertension (PAH) therapy and radical repairs were performed when transcutaneous
      oxygen saturation (SPO2) increased up to 93%. RESULTS: There were no operative
      deaths. SPO2 and baseline six-minute walk test (SMWT) distance of all selected
      patients increased significantly and mean pulmonary artery pressure (MPAP)
      regressed significantly after diagnostic treatment and at late follow-up (P <
      0.01). The incidence of late postoperative PAH was seen in six (10.7%) patients
      and by Logistic regression analysis, early postoperative PAH was an independent
      risk factor related to late postoperative PAH CONCLUSIONS: Diagnostic treatment
      and repair strategy was effective and safe for treatment of nonrestrictive VSD
      and SPAH and the midterm results were excellent. Diagnostic treatment strategy
      was effective in assessing the reversibility of SPAH in older patients associated
      with nonrestrictive VSD and the PVD in these selective patients is generally
      reversible.

PMID- 24571874
TI  - Clinical features and treatment status of hemifacial spasm in China.
AB  - BACKGROUND: Hemifacial spasm (HFS) is a facial nerve disorder characterized by
      episodic involuntary ipsilateral facial muscle contraction. Information on
      Chinese patients with HFS has not been well-characterized. This study aimed to
      evaluate the clinical feature and the treatment status of HFS across China.
      METHODS: A cross-sectional study including 1003 primary HFS patients had been
      carried out in 15 movement disorder clinics in China in 2012. The investigated
      information was acquired from questionnaires and medical records including
      demographic data, site of onset, aggravating and relieving factors, treatments
      prior to the investigation, etc. RESULTS: In this study, the ratio of male to
      female was 1.0:1.8, the mean age at onset was (46.6 +/- 11.5) years. About 1.0%
      patients were bilaterally affected. The most often site of initial onset was the
      orbicularis oculi muscle. The most often affected sites were orbicularis oculi,
      zygomatic, and orbicularis oris muscles. Stress/anxiety and relaxation were most
      often aggravating and relieving factors, respectively; 2.3% patients had family
      history, 28.4% cases were combined with hypertension, and 1.4% patients were with
      trigeminal neuralgia. Botulinum toxin type A (BTX-A) injection was the most
      commonly used treatment, followed by acupuncture and oral medication. BTX-A
      maintained the highest repeat treatment ratio (68.7%), while 98.4% patients gave
      up acupuncture. The mean latency of BTX-A effect was (5.0 +/- 4.7) days, the mean
      total duration of the effect was (19.5 +/- 11.7) weeks, and 95.9% patients
      developed improvements no worse than moderate in both severity and function. The
      most common side effect was droopy mouth. CONCLUSIONS: The onset age of HFS in
      China is earlier than that in western countries. The most often used two
      treatments are BTX-A injection and acupuncture, while the latter kept the poor
      repeat treatment ratio because of dissatisfactory therapeutic effect.

PMID- 24571875
TI  - Effects of plasma ghrelin, obestatin, and ghrelin/obestatin ratio on blood
      pressure circadian rhythms in patients with obstructive sleep apnea syndrome.
AB  - BACKGROUND: Obstructive sleep apnea syndrome (OSAS) is strongly associated with
      obesity and with cardiovascular disease. Ghrelin and obestatin are two peptides
      from the same source but have opposite roles. Both of them can affect feeding and
      regulate vascular tune. The aim of this study was to investigate the relationship
      between plasma ghrelin, obestatin, the ratio of ghrelin and obestatin (G/O) and
      sleep parameters and blood pressure circadian rhythms in patients with OSAS.
      METHODS: This study enrolled 95 newly diagnosed over-weight OSAS patients (OSAS
      group), 30 body mass index (BMI)-match non-OSAS adults (over-weight group) and 30
      non-OSAS normal weight adults (control group). Polysomnography (PSG) was
      performed in the OSAS group and over-weight group. Blood pressure of all subjects
      was monitored by means of 24-hour ambulatory blood pressure monitoring. The
      concentration of plasma ghrelin and obestatin was detected by enzyme-linked
      immunosorbent assay (ELISA). RESULTS: Plasma ghrelin levels in the OSAS group and
      over-weight group were significantly lower than that of the control group (P <
      0.05). Plasma obestatin levels were lower in the over-weight group and OSAS
      group, but there was no significant difference among the three groups. The blood
      pressure in OSAS patients was higher, and there was a significant difference in
      all blood pressure parameters compared to the control group, and in the daytime
      average diastolic blood pressure (DBP), nocturnal average systolic blood pressure
      (SBP) and DBP, DBP variability values as compared to over-weight subjects.
      Furthermore, there were significantly more non-dipper patterns of blood pressure
      (including hypertension and normotension) in the OSAS group than in the other two
      groups (P < 0.01). Correlation analysis showed that ghrelin levels had a
      significant correlation with BMI and nocturnal average DBP but not with PSG
      parameters. In contrast, the G/O ratio had a negative correlation with apnea
      hypopnea index (AHI) (P < 0.05), as well as a strong positive correlation with
      the blood pressure variability values (P < 0.01). In multivariate analyses, AHI
      (P < 0.05) and G/O (P < 0.05) were independently related to SBP variability
      changes, while AHI (P < 0.05), G/O (P < 0.01) and BMI (P < 0.05) were
      independently related to DBP variability changes. CONCLUSIONS: Our data show
      plasma ghrelin and obestatin levels were related to obesity in OSAS. Sleep apnea
      in OSAS patients could have led to an imbalance in G/O in the basis of obesity.
      Moreover, the imbalance may promote nighttime blood pressure elevation and affect
      blood pressure circadian disorder.

PMID- 24571876
TI  - Krupel-like factor 8 is a potential prognostic factor for pancreatic cancer.
AB  - BACKGROUND: Pancreatic cancer is a lethal disease that is often diagnosed at an
      advanced stage. There is a lack of information to predict the prognosis of
      pancreatic cancer. Kruppel-like factor (KLF) 8 has been found to be deregulated
      in multiple cancers, and its high expression was correlated with poor prognosis.
      However, so far, no information was reported about the expression of KLF8 in
      pancreatic cancer. In the present study, we investigated, possibly for the first
      time, the expression of KLF8 in pancreatic cancer samples and analyzed its
      correlation with clinical parameters and overall survival (OS) rate. METHODS: We
      used immunohistochemical staining to detect KLF8 in 68 samples from patients who
      underwent surgery and its correlation with the clinicopathological
      characteristics. We used Kaplan-Meier curve to analyze the relationship between
      KLF8 expression and the OS time. Univariate analysis was performed in addition to
      multivariate hazard models with clinicopathological features to assess KLF8 as an
      independent prognostic factor. RESULTS: KLF8 was present in the cytoplasm of
      pancreatic cancer cells and 52.9% of the 68 cases had positive expression. KLF8
      expression was not associated with sex, age, tumor location, lymph node stage,
      and metastasis stage, but was associated with tumor stage (P = 0.04). Kaplan
      Meier method demonstrated that patients with negative expression of KLF8 had a
      better prognosis. In univariate and multivariate models, KLF8 was a significant
      predictor of OS in pancreatic cancer. CONCLUSION: Our results revealed that KLF8
      may be a potential prognostic factor for pancreatic cancer.

PMID- 24571877
TI  - Jaundice as a prognostic factor in patients undergoing radical treatment for
      carcinomas of the ampulla of Vater.
AB  - BACKGROUND: Carcinomas of the ampulla of Vater (CAV) is a relatively rare
      malignant gastrointestinal tumor, and its postoperative prognostic factors have
      been well studied. However, as its first symptom, the impact of jaundice on the
      prognosis of CAV is not so clear. This study aims to explore the role of jaundice
      as a prognostic factor in patients undergoing radical treatment for CAV. METHODS:
      The clinical data of 195 patients with CAV who were treated in the Cancer
      Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College,
      from January 1989 to January 2013 were retrospectively analyzed. Among them, 170
      patients with pathologically confirmed CAV entered the statistical analysis.
      Jaundice was defined as a total bilirubin serum concentration of >= 3 mg/dl.
      Result Of these 170 patients, 99 (58.20%) had jaundice at presentation. Jaundice
      showed significant correlations with tumor differentiation (P = 0.002), lymph
      node metastasis (P = 0.016), pancreatic invasion (P = 0.000), elevated
      preoperative CA199 (P = 0.000), depth of invasion (P = 0.000), and tumor stage (P
      = 0.000). There were more patients with pancreatic invasion in the jaundice group
      than in the non-jaundice group. Also, lymph node metastasis was more common in
      the jaundice group (n = 26) than in the non-jaundice group (n = 8). The non
      jaundice group had significant better overall 5-year disease-free survival
      (72.6%) than the jaundice group (41.2%, P = 0.013). Jaundice was not
      significantly correlated with the postoperative bleeding (P = 0.050).
      CONCLUSIONS: Jaundice in patients with CAV often predicts more advanced stages
      and poorer prognoses. Pancreatic invasion and lymph node metastasis are more
      common in CAV patients with jaundice. Jaundice is not a risk factor for
      postoperative bleeding and preoperative biliary drainage cannot reduce the
      incidence of postoperative complications.

PMID- 24571878
TI  - Retroperitoneal laparoendoscopic single-site ureterolithotomy versus conventional
      laparoscopic ureterolithotomy.
AB  - BACKGROUND: Laparoendoscopic single-site (LESS) surgery through the
      retroperitoneal approach has been seldom reported. We aimed to evaluate the
      outcomes of LESS and conventional laparoscopic surgery via the retroperitoneal
      approach in the management of large, impacted ureteral calculi. METHODS: Between
      November 2011 and July 2013, retroperitoneal LESS ureterolithotomy was performed
      in 12 patients using a homemade single-port device comprising a surgical glove
      and several strips of tape. Another 16 patients underwent conventional
      retroperitoneal laparoscopic ureterolithotomy. We compared the operative time,
      complications, and surgical outcomes, retrospectively. RESULTS: All patients were
      completed without conversion to conventional laparoscopic or open surgery. The
      operative time of the LESS group and of the conventional laparoscopic group were
      (125.3 +/- 12.8) minutes and (116.9 +/- 14.4) minutes, respectively (P = 0.119).
      The intraoperative blood loss was (42.9 +/- 8.9) and (43.4 +/- 14.7) ml,
      respectively (P = 0.914). Postoperative radiologic evaluation revealed that the
      stones had been removed completely. Cosmetic results were superior in the LESS
      group (P = 0.001). CONCLUSION: Retroperitoneal LESS ureterolithotomy using a
      homemade single-port device can be considered a feasible and safe alternative to
      conventional laparoscopic ureterolithotomy.

PMID- 24571879
TI  - Atorvastatin attenuates involvement of RhoA/Rho-kinase pathway and NF-kappaB
      activation in hypoxic pulmonary hypertensive rats.
AB  - BACKGROUND: Hypoxic pulmonary hypertension (HPH) contributes to the pathogenesis
      of cardiopulmonary diseases. Several lines of evidence indicate that the Rho
      A/Rho-kinase pathway play an important role in the progress of pulmonary
      hypertension. Stains have been shown exert numerous biological effects that are
      independent of their cholesterol-lowering property. We hypothesized that the Rho
      A/Rho-kinase pathway is involved in the pathogenesis of HPH, and that
      atorvastatin would attenuate involvement of the Rho A/Rho-kinase pathway in a HPH
      rat model. METHODS: Thirty-two Wistar rats were randomly divided into four
      groups: control group, hypoxic group, atovastatin group, and normal saline group.
      The control group was kept in a normoxia environment. The other groups were
      exposed to hypoxia for three weeks. Atovastatin was administered daily via a
      gastric gavage in the atovastatin group. We measured the mean pulmonary arterial
      pressure (mPAP), the ratio of the right ventricular weight to the sum of the
      weights of the left heart ventricle and septum (RV/(LV+S)), arteriole wall
      thickness/vascular external diameter (WT%), vascular area/total vascular area
      (WA%), expression of RhoA and phos-MYPT-1 protein in lung tissue, and NF-kappaB
      activation in pulmonary vascular smooth muscle cells. RESULTS: Compared with the
      control group, mPAP, RV/(LV+S), WT%, WA%, NF-kappaB activation, expression of
      RhoA, and phos-MYPT-1 were increased in the hypoxic and normal saline groups (P <
      0.05). Compared with the hypoxic group, mPAP, RV/(LV+S), WT%, WA%, NF-kappaB
      activation, expression of RhoA, and phos-MYPT-1 were decreased in the atovastatin
      group (P < 0.05). Correlations between phos-MPTY-1 and mPAP, WA%, WT%, and NF
      kappaB activation were all positive. CONCLUSIONS: The Rho A/Rho-kinase pathway
      plays an important role in the development of HPH. Atorvastatin reversed HPH by
      inhibiting the activity of Rho A/Rho-kinase and NF-kappaB.

PMID- 24571880
TI  - Diagnostic values of combination of free running asthma screening test and total
      serum allergen IgE level in children with asthma.
AB  - BACKGROUND: A free running asthma screening test is usually used for screening
      exercise-induced bronchoconstriction. The total serum allergen IgE level can
      reveal the patient's atopy characteristics. Our study is to evaluate the
      diagnostic values of the combination of the two tests in asthmatic children and
      compare this new diagnostic method with the International Study of Asthma and
      Allergies in Childhood (ISSAC) questionnaires and the bronchial provocation test,
      which are popular diagnostic tool for pediatric asthma. METHODS: A total of 773
      school children were recruited in this study. The children's asthma was diagnosed
      by means of a combination of the free running asthma screening test and total
      serum allergen IgE level. The new diagnostic method value was assessed using
      receiver operating characteristic (ROC) curves and compared with other diagnostic
      tools such as ISSAC questionnaires and the bronchial provocation test. RESULTS:
      The AUC of this new diagnostic method was higher than 0.9. When the cut-off value
      of total serum allergen IgE level was >= 47 KU/L, the sensitivity and the
      specificity were 71.4% and 85.1%, respectively, which were better than those of
      either the ISSAC questionnaires or bronchial provocation test. CONCLUSION: The
      combination of the free running asthma screening test and total serum allergen
      IgE level may be an effective diagnostic tool for children's asthma.

PMID- 24571881
TI  - Urodynamic analysis and treatment of male Parkinson's disease patients with
      voiding dysfunction.
AB  - BACKGROUND: Parkinson's disease (PD) is an extrapyramidal neurological disorder.
      Urinary symptoms are frequently present in patients affected by PD. Symptoms such
      as urgency, frequency, nocturia, and urge incontinence significantly impact the
      patient's quality of life. We attempted to investigate the urodynamic changes and
      treatment of male PD patients with voiding dysfunction by means of a review.
      METHODS: Comprehensive urodynamic examinations were performed in 141 male
      patients with PD associated with voiding dysfunction. Appropriate treatments were
      given to subgroups that were divided based on test results, and the changes in
      urodynamic parameters as well as the treatment efficacy were observed. RESULTS:
      Detrusor hyperreflexia without bladder outlet obstruction (BOO) was observed in
      35 patients, who exhibited significant improvements in the international prostate
      symptom score (IPSS), maximum flow rate (Qmax), bladder volume at the first
      desire to void, post-void residual (PVR), and bladder compliance. Detrusor
      hyperreflexia associated with BOO was observed in 59 patients. The patients
      exhibited significant improvements in IPSS, Qmax, PVR, and bladder compliance.
      Detrusor dysfunction without BOO was observed in 19 patients, for whom the IPSS
      and the bladder volume at the first desire to void were improved after treatment.
      Detrusor dysfunction with BOO was found in 28 patients, with no significant
      improvement in the urodynamic parameters after the treatment. CONCLUSIONS:
      Urodynamic examination is recommended for male Parkinson's disease patients with
      voiding dysfunction. Early and effective treatment can improve the bladder
      function and quality of life of these patients.

PMID- 24571882
TI  - A novel method of defective vascular reconstruction using 2-octyl-cyanoacrylate
      and homemade prosthetic component.
AB  - BACKGROUND: Currently, adhesive technique is popular in vascular repair but not
      widely used for defective vessels. This study aimed to determine the feasibility
      and effectiveness of repairing defective vessels with 2-octyl-cyanoacrylate and a
      homemade prosthetic component. METHODS: Homemade prosthetic component consisting
      of expanded polytetrofluoroethylene (ePTFE), terylene film, and homemade soluble
      hollow stent mixed with adhesive can replace autologous graft and suture in
      repairing defective vessels, can fix vessels better using the stent without
      occlusive bleeding. Forty male mongrel dogs were used, 20 for biomechanical tests
      and 20 for animal experiments. In the biomechanical test, dogs were randomly
      divided into two groups (n = 10 each), one group repaired on the two sides of the
      carotid arteries with 2-octyl-cyanoacrylate and homemade component and another
      group repaired with suture and ePTFE. Of the 40 specimens, 10 were used for
      adhesive and 10 for suture specimens for tension strength test, whereas the
      remaining specimens were used for bursting pressure test. In animal experiments,
      dogs were also divided into adhesive and suture groups (n = 10), only of the left
      carotid artery. Recording the operational time, bleeding or not. Vessels were
      tested using color Doppler ultrasound, the inner diameter was measured, and the
      degree of stenosis at 8 weeks was evaluated digital subtraction angiography (DSA)
      were also performed. Specimens were then analyzed histologically. RESULTS: In the
      adhesive and suture groups, the specimens could afford atension strength of
      (23.80 +/- 1.51) N versus (24.60 +/- 1.08) N (P > 0.05), the bursting pressure
      was (52.03 +/- 2.43) kPa versus (50.04 +/- 3.51) kPa (P > 0.05), and the mean
      time of anastomosis was (15.20 +/- 0.55) minutes versus (25.97 +/- 0.58) minutes
      (P < 0.05). One dog in the adhesive group was bleeding from the suture. One dog
      from each group presented with thrombosis at 1 week. After measuring using
      ultrasound, the stenosis degree of all dogs were no more than 30% except the two
      thromboses. DSA and histological observation showed no obvious difference between
      the two groups. CONCLUSION: Defective vascular anastomosis with 2-octyl
      cyanoacrylate and our homemade prosthetic component is feasible, effective,
      timesaving, and easy to master.

PMID- 24571883
TI  - Twelve years' experience and clinical results of using the radial artery for
      coronary revascularization.
AB  - BACKGROUND: The radial artery (RA) is becoming a popular conduit for coronary
      artery bypass grafting (CABG), yet data reporting the long-term results are rare.
      We reported our clinical, angiographic and intravascular ultrasound findings on
      93 patients who had the RA used as part of the conduit for the CABG procedures
      during a 12-year period from June 2001 to June 2013. METHODS: A total of 118
      radial artery conduits were harvested in 87 males and 6 females, age from 28 to
      66 (mean 49.9) years. An "intra-operative Allen's test" was developed to
      safeguard blood supply to the arm and hand. A "double-clip & scissors-cut"
      technique was carried out to minimize the thermal injury to the radial artery
      from the diathermy. The left radial artery was used in 67 patients, the right in
      one, and bilateral radial arteries in 25 patients. One hundred and twenty-two out
      of 272 distal anastomoses (44.9%) were constructed with radial arteries, with an
      average of 2.9 grafts per patient (range 2-6). RESULTS: Follow-up angiography and
      intravascular ultrasound study at 3-139 postoperative months (mean 59 months)
      revealed a 93.1% RA patency. String sign occurred in one patient in whom the RA
      was directed to a big right coronary artery with a stenosis of around 50%. The
      patency for the internal mammary artery was 96.4%. CONCLUSIONS: The RA is an
      excellent conduit that broadens the options for total arterial CABG surgery. Good
      graft patency could be achieved through careful harvesting techniques and choice
      of proper target coronary vessels.

PMID- 24571884
TI  - Potential biomarkers predicting risk of pulmonary hypertension in congenital
      heart disease: the role of homocysteine and hydrogen sulfide.
AB  - BACKGROUND: Pulmonary hypertension (PH) is a common complication of congenital
      heart disease (CHD). Although risk stratification is vital for prognosis and
      therapeutic guidance, the need for understanding the role of novel biomarkers
      cannot be overlooked. The aim of the present study was to investigate the changes
      of homocysteine and hydrogen sulfide levels and find potential biomarkers for
      early detection and treatment. METHODS: Between September 2012 and April 2013, we
      prospectively collected data on 158 pediatric patients with left to right shunt
      CHD at our institution. Standard right heart catheterizations were performed in
      all cases. Seventy-seven cases were associated with PH. The levels of
      homocysteine and hydrogen sulfide were detected with fluorescence polarization
      immunoassay and a sensitive silver-sulphur electrode, respectively. Enzyme-linked
      immunosorbent assay was used to determine the expression of
      methylenetetrahydrofolate reductase (MTHFR), cystathionine beta-synthase (CBS),
      and cystathionine gamma-lyase (CSE). Radioimmunoassays were used to obtain folic
      acid and vitamin B12 levels. RESULTS: The difference in the levels of
      homocysteine, folic acid, vitamin B12, hydrogen sulfide, as well as the MTHFR and
      CSE expression between patients with PH and without PH were statistically
      significant (all P < 0.05). Homocysteine had the best sensitivity and specificity
      to predict PH (P < 0.001). Subgroup analysis showed that the levels of
      homocysteine and hydrogen sulfide, and the expression of CSE and MTHFR between
      patients with dynamic and obstructive PH were significantly different (all P <
      0.05). Based on the ROC curve, homocysteine had the best sensitivity and
      specificity to predict obstructive PH (P = 0.032), while CSE had the most
      significant sensitivity and specificity to predict the dynamic PH (P = 0.008).
      CONCLUSIONS: Increased levels of homocysteine and decreased levels of hydrogen
      sulfide were significantly negatively correlated in PH associated with CHD. The
      underlying mechanism involved the decreased expression of MTHFR and CSE along
      with vitamin B12 deficiency. Homocysteine and hydrogen sulfide are potential
      biomarkers to predict PH.

PMID- 24571885
TI  - Risk factors associated with emergency peripartum hysterectomy.
AB  - BACKGROUND: Use of an emergency peripartum hysterectomy (EPH) as a lifesaving
      measure to manage intractable postpartum hemorrhage (PPH) appears to be
      increasing recently around the world, and the indications for EPH have changed.
      The object of this study is to identify risk factors associated with EPH.
      METHODS: We conducted a case-control study of 21 patients who underwent EPH
      because of intractable PPH between January 1, 2005 and June 30, 2013, at the
      International Peace Maternity and Child Health Hospital Shanghai Jiao Tong
      University, School of Medicine (IPMCH). The parametric t-test, chi-square tests
      and Logistic regression models were used for analysis to identify the risk
      factors. The results were considered statistically significant when P < 0.05.
      RESULTS: There were 89 178 deliveries during the study period. Twenty-one women
      had an EPH, with an incidence of 24 per 100 000 deliveries. The loss of blood
      during postpartum hemorrhage of the EPH group was (5 060.7 +/- 3 032.6) ml, and
      that of the control group was (2 040.8 +/- 723.5) ml. There was a significant
      difference of PHH between the EHP group and the control group (P = 0.001).
      Independent risk factors for EPH from a logistic regression model were:
      disseminated intravascular coagulation (DIC) (OR: 9.9, 95% CI 2.8-34, P = 0.003),
      previous cesarean section (OR: 5.27; 95% CI: 1.48-17.9, P = 0.009), placenta
      previa (OR: 6.9; 95% CI 1.6-2.9, P = 0.008), the loss of PPH (OR: 1.001; 95% CI
      1.001-1.002, P = 0.002), placenta accreta (OR: 68; 95% CI 10-456, P = 0.004), the
      use of tocolytic agents prenatally (OR: 6.55, 95%CI 1.34-32.1,P = 0.049), and
      fetal macrosomia (OR: 6.9, 95% CI 1.25-38, P = 0.049). CONCLUSION: Significant
      risk factors of EPH are DIC, placenta previa, PPH, previous cesarean delivery,
      and placenta accrete, the use of tocolytic agents prenatally, and fetal
      macrosomia.

PMID- 24571886
TI  - Safety and efficacy of bimatoprost/timolol fixed combination in Chinese patients
      with open-angle glaucoma or ocular hypertension.
AB  - BACKGROUND: Lowering intraocular pressure (IOP) is currently the only therapeutic
      approach in primary open-angle glaucoma. and the fixed-combination medications
      are needed to achieve sufficiently low target IOP. A multicenter prospective
      study in the Chinese population was needed to confirm the safety and efficacy of
      Bimatoprost/Timolol Fixed Combination Eye Drop in China. In this study, we
      evaluated the safety and efficacy of Bimatoprost/Timolol Fixed Combination with
      concurrent administration of its components in Chinese patients with open-angle
      glaucoma or ocular hypertension. METHODS: In this multicenter, randomized, double
      masked, parallel controlled study, patients with open-angle glaucoma or ocular
      hypertension who were insufficiently responsive to monotherapy with either
      topical beta-blockers or prostaglandin analogues were randomized to one of two
      active treatment groups in a 1:1 ratio at 11 Chinese ophthalmic departments.
      Bimatoprost/timolol fixed combination treatment was a fixed combination of 0.03%
      bimatoprost and 0.5% timolol (followed by vehicle for masking) once daily at
      19:00 P.M. and concurrent treatment was 0.03% bimatoprost followed by 0.5%
      timolol once daily at 19:00 P.M. The primary efficacy variable was change from
      baseline in mean diurnal intraocular pressure (IOP) at week 4 visit in the intent
      to-treat (ITT) population. Primary analysis evaluated the non-inferiority of
      bimatoprost/ timolol fixed combination to concurrent with respect to the primary
      variable using a confidence interval (CI) approach. Bimatoprost/timolol fixed
      combination was to be considered non-inferior to concurrent if the upper limit of
      the 95% CI for the between-treatment (bimatoprost/timolol fixed combination minus
      concurrent) difference was <= 1.5 mmHg. Adverse events were collected and slit
      lamp examinations were performed to assess safety. Between-group comparisons of
      the incidence of adverse events were performed using the Pearson chi-square test
      or Fisher's exact test. RESULTS: Of the enrolled 235 patients, 121 patients were
      randomized to receive bimatoprost/timolol fixed combination and, 114 patients
      were randomized to receive concurrent treatment. At baseline the mean value of
      mean diurnal IOP was (25.20 +/- 3.06) mmHg in the bimatoprost/timolol fixed
      combination group and (24.87 +/- 3.88) mmHg in the concurrent group. The
      difference between the treatment groups was not statistically significant. The
      mean change from baseline in mean diurnal IOP (+/- standard deviation) in the
      bimatoprost/timolol fixed combination group was (-9.38 +/- 4.66) mmHg and it was
      (-8.93 +/- 4.25) mmHg in the concurrent group (P < 0.01). The difference between
      the two treatment groups (bimatoprost/timolol fixed combination minus concurrent)
      in the change from baseline of mean diurnal IOP was -0.556 mmHg (95% CI: -1.68,
      0.57, P = 0.330). The upper limit of the 95% CI was less than 1.5 mmHg, the
      predefined margin of non-inferiority. Adverse events occurred in 26.4% (32/121)
      of the bimatoprost/timolol fixed combination patients and 30.7% (35/114) of the
      concurrent patients. The most frequent adverse event was conjunctival hyperemia,
      which was reported as treatment related in 16.5% (20/121) in the
      bimatoprost/timolol fixed combination group and 18.4% (21/114) in the concurrent
      group (P > 0.05). CONCLUSIONS: Bimatoprost/Timolol Fixed Combination administered
      in Chinese patients with open-angle glaucoma or ocular hypertension was not
      inferior to concurrent dosing with the individual components. Safety profiles
      were similar between the treatment groups.

PMID- 24571887
TI  - A comparison of implantation, miscarriage and pregnancy rates of single and
      double day 3 embryo transfer between fresh and frozen thawed transfer cycles: a
      retrospective study.
AB  - BACKGROUND: Reduced endometrial receptivity in hyperstimulated cycles may lead to
      a lower implantation rate and a lower clinical pregnancy rate, but it is unclear
      if it is also associated with an increase in pregnancy loss rate. The aim of this
      study was to compare the implantation, miscarriage, and pregnancy rates between
      fresh and frozen thawed transfer of one or two day-3 embryos, with a view to
      understanding whether or not reduced endometrial receptivity encountered in
      hyperstimulated cycles is associated with an increase in miscarriage rate.
      METHODS: This study involved a consecutive series of 1 551 single day-3 embryo
      transfer cycles and consecutive 5 919 double day-3 embryo transfer cycles in the
      Assisted Reproductive Unit of the Sir Run Run Shaw Hospital, Hangzhou, China,
      between January 2010 and December 2012. RESULTS: The implantation and clinical
      pregnancy rates (single embryo 30.7% and double embryos 33.4% and 51.4%) using
      fresh cycle were both significantly lower than that of frozen-thawed cycles
      (single embryo 35.8% and double embryos 38.1% and 57.8%). There was no difference
      in biochemical loss or clinical miscarriage rates between the two groups.
      CONCLUSIONS: Impairment of endometrial receptivity associated with ovarian
      hyperstimulation leads to implantation failure at a very early stage, resulting
      in an increased number of non-pregnancy. It does not lead to increase in
      biochemical or clinical losses. The significantly reduced ongoing pregnancy rates
      in both fresh single and double embryo transfer are therefore due to failure to
      achieve a pregnancy, rather than pregnancy loss after conception.

PMID- 24571888
TI  - Relationship between [corrected] spatial memory in diabetic rats and protein
      kinase Cgamma, caveolin-1 in the hippocampus and neuroprotective effect of
      catalpol.
AB  - BACKGROUND: The mechanisms underlying diabetic encephalopathy are largely
      unknown, and no effective treatments are available. Catalpol has received much
      attention due to its numerous biological effects, especially in neuroprotective
      studies. The aim of this study was to investigate the effects of catalpol on
      cognitive functions in diabetic rats and the underlying mechanisms. METHODS: A
      rat model of diabetes was established by streptozotocin injection, followed by
      intraperitoneal infusion of catalpol after 10 weeks. Two weeks later, the Morris
      water maze was used to test the spatial learning performance. Nissl staining was
      performed to evaluate the morphological changes in the hippocampus. Expression of
      protein kinase Cgamma (PKCgamma) and caveolin-1 (Cav-1) in the hippocampus were
      assessed by reverse transcription PCR and Western blotting. Activities of anti
      oxidative enzymes such as glutathione (GSH), superoxide dismutase (SOD) and
      catalase (CAT) and levels of malonaldehyde (MDA) were measured using commercial
      kits. RESULTS: Significant hippocampal neuronal injury was observed in rats with
      streptozotocin-induced diabetes. Moreover, cognitive dysfunction was associated
      with markedly increased oxidative stress in the brain. Catalpol treatment
      significantly attenuated cognitive deficits, neuronal damage, and oxidative
      stress in the brain of diabetic rats. Biochemical analyses showed that catalpol
      reversed the down-regulation of PKCgamma and Cav-1 expression in the diabetic
      rats. CONCLUSIONS: Spatial memory in diabetic rats is associated with the
      expression of PKCgamma and Cav-1. Catalpol treatment markedly attenuated
      oxidative stress, reversed the alteration of PKCgamma, Cav-1 and spatial memory
      deficits.

PMID- 24571889
TI  - Gamma-secretase inhibitor DAPT prevents neuronal death and memory impairment in
      sepsis associated encephalopathy in septic rats.
AB  - BACKGROUND: Brain dysfunction is a frequent complication of sepsis, usually
      defined as sepsis-associated encephalopathy (SAE). Although the Notch signaling
      pathway has been proven to be involved in both ischemia and neuronal
      proliferation, its role in SAE is still unknown. Here, the effect of the Notch
      signaling pathway involved gamma-secretase inhibitor DAPT on SAE in septic rats
      was investigated in a cecal ligation and puncture (CLP) model. METHODS: Fifty
      nine Sprague-Dawley rats were randomly divided into four groups, with the septic
      group receiving the CLP operation. Twenty-four hours after CLP or sham treatment,
      rats were sacrificed and their hippocampus was harvested for Western blot
      analysis. TNF-alpha expression was determined using an enzyme-linked
      immunosorbent assay (ELISA) kit. Neuronal apoptosis was assessed by TUNEL
      staining, and neuronal cell death was detected by H&E staining. Finally, a novel
      object recognition experiment was used to evaluate memory impairment. RESULTS:
      Our data showed that sepsis can increase the expression of hippocampal Notch
      receptor intracellular domain (NICD) and poly (adenosine diphosphate [ADP]
      ribose) polymerase-1 (PARP-1), as well as the inflammatory response, neuronal
      apoptosis, neuronal death, and memory dysfunction in rats. The gamma-secretase
      inhibitor N-[N-(3,5-difluorophenacetyl)-1-alanyl]-S-phenylglycine t-butyl ester
      (DAPT) can significantly decrease the level of NICD and PARP-1, reduce
      hippocampal neuronal apoptosis and death, attenuate TNF-alpha release and rescue
      cognitive impairment caused by CLP. CONCLUSION: The neuroprotective effect of
      DAPT on neuronal death and memory impairment in septic rats, which could be a new
      therapeutic approach for treating SAE in the future.

PMID- 24571890
TI  - Prostate specific membrane antigen knockdown impairs the tumorigenicity of LNCaP
      prostate cancer cells by inhibiting the phosphatidylinositol 3-kinase/Akt
      signaling pathway.
AB  - BACKGROUND: Prostate specific membrane antigen (PSMA) can facilitate the growth,
      migration, and invasion of the LNCaP prostate cancer cell lines, but the
      underlying molecular mechanisms have not yet been clearly defined. Here, we
      investigated whether PSMA serves as a novel regulator of the phosphatidylinositol
      3-kinase (PI3K)/Akt signaling by employing PSMA knockdown model and PI3K
      pharmacological inhibitor (LY294002) in LNCaP prostate cancer cells. METHODS:
      PSMA knockdown had been stably established by transfecting with lentivirus
      mediated siRNA in our previous study. Then, LNCaP cells were divided into
      interference, non-interference, and blank groups. We first testified the efficacy
      of PSMA knockdown in our LNCaP cell line. Then, we compared the expression of
      PSMA and total/activated Akt by Western blotting in the above three groups with
      or without LY294002 treatment. Furthermore, immunocytochemistry was performed to
      confirm the changes of activated Akt (p-Akt, Ser473) in groups. Besides, cell
      proliferation, migration, and cell cycle were measured by CCK-8 assay, Transwell
      analysis, and Flow cytometry respectively. RESULTS: After PSMA knockdown, the
      level of p-Akt (Ser473) but not of total-Akt (Akt1/2) was significantly decreased
      when compared with the non-interference and blank groups. However, LY294002
      administration significantly reduced the expression of p-Akt (Ser473) in all the
      three groups. The results of immunocytochemistry further confirmed that PSMA
      knockdown or LY294002 treatment was associated with p-Akt (Ser473) down
      regulation. Decrease of cell proliferation, migration, and survival were also
      observed upon PSMA knockdown and LY294002 treatment. CONCLUSIONS: Taken together,
      our results reveal that PI3K/Akt signaling pathway inhibition may serve as a
      novel molecular mechanism in LNCaP prostate cancer cells of PSMA knockdown and
      suggest that Akt (Ser473) may play a critical role as a downstream signaling
      target effector of PSMA in this cellular model.

PMID- 24571891
TI  - Changes in energy metabolism in the quadriceps femoris after a single bout of
      acute exhaustive swimming in rats: a 31P-magnetic resonance spectroscopy study.
AB  - BACKGROUND: Little is known about the value of (31)P-magnetic resonance
      spectroscopy ((31)P-MRS) in in vivo assessment of exhaustive exercise-induced
      injury in skeletal muscle. We aimed to evaluate the value of a (31)P-MRS study
      using the quadriceps femoris after a single bout of acute exhaustive swimming in
      rats, and the correlation between (31)P-MRS and histological changes. METHODS:
      Sixty male Sprague-Dawley rats were randomly assigned to control, half
      exhaustive, and exhaustive exercise groups. (31)P-MRS of the quadriceps femoris
      of the right lower limb was performed immediately after swimming exercise to
      detect Pi, PCr, and beta-ATP. The Pi/PCr, Pi/beta-ATP, PCr/beta-ATP, and
      PCr/(PCr+Pi) were calculated and pH measured. Areas under the receiver operating
      characteristic curve (AUCs) were calculated to evaluate the diagnostic potential
      of (31)P-MRS in identifying and distinguishing the three groups. HE staining,
      electron microscopy and desmin immunostaining after imaging of the muscle were
      used as a reference standard. The correlation between (31)P-MRS and the mean
      absorbance (A value) of desmin staining were analyzed with the Pearson
      correlation test. RESULTS: Pi, PCr, Pi/PCr, and PCr/(PCr+Pi) showed statistically
      significant intergroup differences (P < 0.05). AUCs of Pi, PCr, Pi/PCr, and
      PCr/(PCr+Pi) were 0.905, 0.848, 0.930, and 0.930 for the control and half
      exhaustive groups, while sensitivity and specificity were 90%/85%, 95%/55%,
      95%/80%, and 90%/85%, respectively. The AUCs of Pi, PCr, Pi/PCr and PCr/(PCr+Pi)
      were 0.995, 0.980, 1.000, and 1.000 for the control and exhaustive groups, while
      sensitivity and specificity were 95%/90%, 100%/90%, 100%/95%, and 100%/95%,
      respectively. The AUCs of Pi, PCr, Pi/PCr, and PCr/(PCr+Pi) were 0.735, 0.865,
      0.903, and 0.903 for the half-exhaustive and exhaustive groups, while sensitivity
      and specificity were 80%/60%, 90%/75%, 95%/65%, and 95%/70%, respectively. In the
      half-exhaustive group, some muscle fibers exhibited edema in HE staining, and the
      unclear Z-discs and the mitochondria with vacuolar degeneration under electron
      microscopy. Compared with the half-exhaustive group, muscle fiber edema was
      increased in the exhaustive group, and the Z-discs were broken and the
      mitochondria exhibited marked vacuolar degeneration under electron microscopy.
      There were significant difference in A values of desmin staining in the right
      vastus lateralis among the control, half-exhaustive, and exhaustive groups with
      0.58 +/- 0.06, 0.30 +/- 0.04, and 0.21 +/- 0.02, respectively (P < 0.05).
      Histological examination also showed injury-induced changes in the vastus
      lateralis among the different intensities groups. Statistically a moderate
      correlation between (31)P-MRS and desmin was observed, the correlation
      coefficients of Pi, PCr, Pi/PCr, and PCr/(PCr+Pi) were -0.706, 0.709, -0.726, and
      0.791, respectively (P < 0.01). CONCLUSIONS: (31)P-MRS can effectively reflect
      the changes in energy metabolism in the skeletal muscle after a single bout of
      acute exhaustive swimming in rats. Based on the significant correlation between
      (31)P-MRS parameters and histological changes, the changes of Pi, PCr, Pi/PCr,
      and PCr/(PCr+Pi) can indirectly reflect the degree of exercise-induced injury.

PMID- 24571892
TI  - Relation of myocardial bridge to myocardial infarction: a meta-analysis.
AB  - BACKGROUND: Small case series have suggested an association of coronary
      myocardial bridge (MB) with myocardial infarction (MI). However, the relationship
      between MB and major adverse cardiac events (MACE) remains largely unknown. The
      aim of this study was to assess the relationship between MB and MACE involving
      MI. METHODS: We performed a systematic search of MEDLINE, PreMEDLINE, and all EMB
      Reviews as well as a reference list of relevant articles according to the SPICO
      (Study design, Patient, Intervention, Control-intervention, and Outcome) criteria
      using the following keywords: myocardial bridging, myocardial bridge, intramural
      coronary artery, mural coronary artery, tunneled coronary artery, coronary artery
      overbridging, etc. Bibliographies of the retrieved publications were additionally
      hand searched. Studies were included for the meta-analysis if they satisfied the
      following criteria: (1) they evaluate the association of MB with cardiovascular
      endpoint event; (2) they included individuals with MB and those without MB; 3)
      they excluded individuals with obstructive coronary artery disease (CAD). Studies
      were reviewed by a predetermined protocol including quality assessment. Dates
      were pooled using a random effect model. RESULTS: Seven observational studies
      that followed 5 486 patients eligible for the enrolled criteria were included
      from 7 136 initially identified articles. The prevalence of MB was 24.8% (1 363/5
      486). During 0.5-7.0 years of follow-up of this cohort of population, crude
      outcome rates were 8.0% in the MB group and 7.7% in the non-MB group. The odds
      ratio of overall MACE and MI were 1.34 (95% confidence interval (CI): 0.57-3.17,
      P = 0.51, n = 7 studies) and 2.75 (95% CI: 1.08-7.02, P < 0.03, n = 5 studies)
      respectively for subjects of MB compared to non-MB. CONCLUSION: Relationship
      between MB and MI appears to be a real one, although the study did not reveal a
      connection of MB to MACE, suggesting whether the necessity of antiplatelet
      therapy needs to be further studied in a larger cohort of patients with MB
      prospectively.

PMID- 24571893
TI  - Chemotherapy with or without irinotecan in patients with advanced or recurrent
      gastric cancer: a meta-analysis of randomized controlled trials.
AB  - BACKGROUND: Studies have shown that irinotecan can improve survival in patients
      with advanced or recurrent gastric cancer, but the overall benefit of irinotecan
      in the treatment of advanced or recurrent gastric cancer remains controversial.
      The aim of this study was to evaluate the benefits and risks of irinotecan for
      survival in patients with advanced or recurrent gastric cancer. Method We
      searched PubMed, EmBase, the Cochrane Central Register of Controlled Trials,
      reference lists of articles, and proceedings of major conferences for relevant
      clinical trials. We included randomized controlled trials that reported on the
      efficacy and safety of irinotecan in patients with advanced or recurrent gastric
      cancer. Outcomes were analyzed by survival rate, objective response rate (ORR),
      and toxicity. Furthermore, the analysis was further stratified by factors that
      could affect the treatment effects. RESULTS: Eight trials recruiting 1 546
      patients with advanced or recurrent gastric cancer were included in the analysis.
      Overall, irinotecan therapy was associated with a 6% improvement in survival
      rate, but this difference was not statistically significant (odds ratio (OR)
      0.94; 95% confidence interval (95% CI) 0.70-1.27; P = 0.69). However, irinotecan
      therapy had more frequent ORR than irinotecan-free arm (OR 1.70; 95% CI 1.34
      2.17; P < 0.001). Furthermore, irinotecan therapy was associated with a
      clinically and statistically significant increase in the risk for declined
      hemoglobin, hyponatremia, and diarrhea, but it also protected against
      thrombocytopenia risk when compared with irinotecan-free therapy. CONCLUSIONS:
      There is no evidence to support the use of irinotecan therapy in patients with
      advanced or recurrent gastric cancer; however, given the significant advantage in
      ORR irinotecan therapy using combination regimens may be considered for further
      evaluation in subsets of patients who may benefit from this treatment.

PMID- 24571894
TI  - Treatment strategies for locally advanced prostate cancer.

PMID- 24571895
TI  - Clinical study on eye metastasis in patients with breast cancer.

PMID- 24571896
TI  - Edaravone rescues the lung by inhibiting lipid peroxidation and pro-inflammatory
      cytokines in a rat model.

PMID- 24571897
TI  - ABO sequence analysis in an AB type with anti-B patient.

PMID- 24571898
TI  - Profile of the levonorgestrel-releasing intrauterine system users in China.

PMID- 24571900
TI  - Mini-culotte stenting for bifurcation coronary disease.

PMID- 24571899
TI  - Effects of low doses of aerosolized iloprost combined with tadalafil in treatment
      of adult congenital heart disease with severe pulmonary arterial hypertension.

PMID- 24571901
TI  - Successful management of an incarcerated left-sided Amyand's hernia in a 63-year
      old male.

PMID- 24571902
TI  - A novel case of Hyper IgE syndrome combined with natural killer cell deficiency.

PMID- 24571903
TI  - Mesonephric adenocarcinoma of the vaginal-urethral interspace.

PMID- 24571905
TI  - Surgical treatment of hairy polyp in the Eustachian tube.

PMID- 24571904
TI  - Vascular stent as a treatment for refractory cervical stenosis.

PMID- 24571906
TI  - Severe airway obstruction caused by tonsillar polyp in anesthetized patient.

PMID- 24571907
TI  - Noninvasive assessment of renal fractional flow reserve: are we there yet?

PMID- 24571908
TI  - Enhancement of the scientific management of earthquake disaster rescue: improving
      the state level of disaster medical care.

PMID- 24571909
TI  - Aggressive angiomyxoma of the vagina.

PMID- 24571910
TI  - Thrombolysis during prolonged resuscitation after cardiac arrest caused by
      presumed pulmonary embolism.

PMID- 24571911
TI  - Cutaneous metastasis of breast cancer previously diagnosed 25 years ago.

PMID- 24571912
TI  - Physiological changes induced by salt intake in female Spontaneously Diabetic
      Torii-Lepr(fa) (SDT fatty) rat, a novel obese type 2 diabetic model.
AB  - Salt plays an important role in the control of blood pressure in obesity and
      diabetes mellitus. In this study, we investigated physiological changes such as
      blood pressure and renal function in salt-loaded female Spontaneously Diabetic
      Torii-Lepr(fa) (SDT fatty) rats. SDT fatty rats were given 1% NaCl in drinking
      water for 14 weeks, from 4 to 18 weeks of age. Significant salt-sensitive
      hypertension was observed in the salt-loaded SDT fatty rats. Moreover, the salt
      loaded rats showed a decrease of creatinine clearance and deterioration on
      pathological renal findings, including glomerulosclerosis and tubular and
      interstitial lesions. Female SDT fatty rat is a useful model for investigating
      the mechanisms of high salt sensitivity in obesity and diabetes mellitus. 

PMID- 24571913
TI  - Evaluation of volumetric modulated arc therapy for postmastectomy treatment.
AB  - PURPOSE: To examine the feasibility of volumetric modulated arc therapy (VMAT)
      for post mastectomy radiotherapy (PMRT). METHODS AND MATERIALS: Fifteen PMRT
      patients previously treated at our clinic with helical tomotherapy (HT) were
      identified for the study. Planning target volumes (PTV) included the chest wall
      and regional lymph nodes. A systematic approach to constructing VMAT that met the
      clinical goals was devised. VMAT plans were then constructed for each patient and
      compared with HT plans with which they had been treated. The resulting plans were
      compared on the basis of PTV coverage; dose homogeneity index (DHI) and
      conformity index (CI); dose to organs at risk (OAR); tumor control probability
      (TCP), normal tissue complication probability (NTCP) and secondary cancer
      complication probability (SCCP); and treatment delivery time. Differences were
      tested for significance using the paired Student's t-test. RESULTS: Both
      modalities produced clinically acceptable PMRT plans. VMAT plans showed better CI
      (p<0.01) and better OAR sparing at low doses than HT plans, particularly at doses
      less than 5 Gy. On the other hand, HT plans showed better DHI (p<0.01) and showed
      better OAR sparing at higher doses. Both modalities achieved nearly 100% tumor
      control probability and approximately 1% NTCP in the lungs and heart. VMAT showed
      lower SCCP than HT (p<0.01), though both plans showed higher SCCP values than
      conventional mixed beam (electron-photon) plans reported by our group previously.
      VMAT plans required 66.2% less time to deliver than HT. CONCLUSIONS: Both VMAT
      and HT provide acceptable treatment plans for PMRT. Both techniques are currently
      utilized at our institution.

PMID- 24571914
TI  - Are public health organizations tweeting to the choir? Understanding local health
      department Twitter followership.
AB  - BACKGROUND: One of the essential services provided by the US local health
      departments is informing and educating constituents about health. Communication
      with constituents about public health issues and health risks is among the
      standards required of local health departments for accreditation. Past research
      found that only 61% of local health departments met standards for informing and
      educating constituents, suggesting a considerable gap between current practices
      and best practice. OBJECTIVE: Social media platforms, such as Twitter, may aid
      local health departments in informing and educating their constituents by
      reaching large numbers of people with real-time messages at relatively low cost.
      Little is known about the followers of local health departments on Twitter. The
      aim of this study was to examine characteristics of local health department
      Twitter followers and the relationship between local health department
      characteristics and follower characteristics. METHODS: In 2013, we collected
      (using NodeXL) and analyzed a sample of 4779 Twitter followers from 59 randomly
      selected local health departments in the United States with Twitter accounts. We
      coded each Twitter follower for type (individual, organization), location, health
      focus, and industry (eg, media, government). Local health department
      characteristics were adopted from the 2010 National Association of City and
      County Health Officials Profile Study data. RESULTS: Local health department
      Twitter accounts were followed by more organizations than individual users.
      Organizations tended to be health-focused, located outside the state from the
      local health department being followed, and from the education, government, and
      non-profit sectors. Individuals were likely to be local and not health-focused.
      Having a public information officer on staff, serving a larger population, and
      "tweeting" more frequently were associated with having a higher percentage of
      local followers. CONCLUSIONS: Social media has the potential to reach a wide and
      diverse audience. Understanding audience characteristics can help public health
      organizations use this new tool more effectively by tailoring tweet content and
      dissemination strategies for their audience.

PMID- 24571915
TI  - Physical activity and inactivity patterns in India - results from the ICMR-INDIAB
      study (Phase-1) [ICMR-INDIAB-5].
AB  - BACKGROUND: The rising prevalence of diabetes and obesity in India can be
      attributed, at least in part, to increasing levels of physical inactivity.
      However, there has been no nationwide survey in India on physical activity levels
      involving both the urban and rural areas in whole states of India. The aim of the
      present study was to assess physical activity patterns across India - as part of
      the Indian Council of Medical Research-India Diabetes (ICMR-INDIAB) study.
      METHODS: Phase 1 of the ICMR-INDIAB study was conducted in four regions of India
      (Tamilnadu, Maharashtra, Jharkhand and Chandigarh representing the south, west,
      east and north of India respectively) with a combined population of 213 million
      people. Physical activity was assessed using the Global Physical Activity
      Questionnaire (GPAQ) in 14227 individuals aged >= 20 years [urban- 4,173; rural-
      10,054], selected from the above regions using a stratified multistage design.
      RESULTS: Of the 14227 individuals studied, 54.4% (n=7737) were inactive (males:
      41.7%), while 31.9% (n=4537) (males: 58.3%) were active and 13.7% (n=1953)
      (males: 61.3%) were highly active. Subjects were more inactive in urban, compared
      to rural, areas (65.0% vs. 50.0%; p<0.001). Males were significantly more active
      than females (p<0.001). Subjects in all four regions spent more active minutes at
      work than in the commuting and recreation domains. Absence of recreational
      activity was reported by 88.4%, 94.8%, 91.3% and 93.1% of the subjects in
      Chandigarh, Jharkhand, Maharashtra and Tamilnadu respectively. The percentage of
      individuals with no recreational activity increased with age (Trend chi(2):
      199.1, p<0.001). CONCLUSIONS: The study shows that a large percentage of people
      in India are inactive with fewer than 10% engaging in recreational physical
      activity. Therefore, urgent steps need to be initiated to promote physical
      activity to stem the twin epidemics of diabetes and obesity in India.

PMID- 24571916
TI  - Predictors of functional response and remission with desvenlafaxine 50 mg/d in
      patients with major depressive disorder.
AB  - BACKGROUND: The predictive value of early functional improvement for treatment
      success at week 8 was assessed in a pooled analysis in patients with major
      depressive disorder (MDD). METHODS: Data were pooled from 7 double-blind studies
      in adult patients with MDD randomly assigned to desvenlafaxine 50 mg/d or
      placebo. Four levels of treatment success were determined at week 8 for patients
      with baseline Sheehan Disability Scale (SDS) score > 12 (N = 2156): functional
      response (SDS <=12 and >=50% improvement in SDS), functional/depression response
      (SDS <=12 and >=50% improvement in both SDS and 17-item Hamilton Rating Scale for
      Depression [HAM-D17] score), functional remission (SDS < 7), and
      functional/depression remission (SDS < 7 and HAM-D17 <=7). Week 2 improvement in
      SDS was evaluated as a predictor of later functional response/remission using
      receiver operating characteristic analysis. Odds ratios (ORs) of the
      predictability of improvement thresholds were computed from a logistic regression
      model. RESULTS: The proportion of patients achieving each level of treatment
      success was significantly greater for patients treated with desvenlafaxine (40%,
      32%, 23%, 15%, respectively) vs placebo (31%, 22%, 17%, 10%; all P <= 0.002).
      Early change in SDS was a highly significant predictor of functional
      response/remission (ORs, 0.958-0.970; all P < 0.0001). Discussion Patients' early
      functional response to desvenlafaxine 50 mg/d is predictive of treatment success.

PMID- 24571917
TI  - Effect of recovery interventions on cycling performance and pacing strategy in
      the heat.
AB  - PURPOSE: To determine the effect of active recovery (AR), passive rest (PR), and
      cold-water immersion (CWI) after 90 min of intensive cycling on a subsequent 12
      min time trial (TT2) and the applied pacing strategy in TT2. METHODS: After a
      maximal test and familiarization trial, 9 trained male subjects (age 22 +/- 3 y,
      VO2max 62.1 +/- 5.3 mL . min-1 . kg-1) performed 3 experimental trials in the
      heat (30 degrees C). Each trial consisted of 2 exercise tasks separated by 1 h.
      The first was a 60-min constant-load trial at 55% of the maximal power output
      followed by a 30-min time trial (TT1). The second comprised a 12-min simulated
      time trial (TT2). After TT1, AR, PR, or CWI was applied for 15 min. RESULTS: No
      significant TT2 performance differences were observed, but a 1-sample t test
      (within each condition) revealed different pacing strategies during TT2. CWI
      resulted in an even pacing strategy, while AR and PR resulted in a gradual
      decline of power output after the onset of TT2 (P <= .046). During recovery, AR
      and CWI showed a trend toward faster blood lactate ([BLa]) removal, but during
      TT2 significantly higher [BLa] was only observed after CWI compared with PR (P =
      .011). CONCLUSION: The pacing strategy during subsequent cycling performance in
      the heat is influenced by the application of different postexercise recovery
      interventions. Although power was not significantly altered between groups, CWI
      enabled a differently shaped power profile, likely due to decreased thermal
      strain.

PMID- 24571918
TI  - An analysis of reported motivational orientation in students undertaking doctoral
      studies in the biomedical sciences.
AB  - BACKGROUND: As the source of a sizeable percentage of research output and the
      future arbiters of science policy, practice and direction, doctoral (Ph.D.)
      students represent a key demographic in the biomedical research community.
      Despite this, doctoral learning in the biomedical sciences has, to date, received
      little research attention. METHODS: In the present study we aimed to
      qualitatively describe the motivational orientations present in semi-structured
      interview transcripts from a cohort of seventeen biomedical Ph.D. students drawn
      from two research intensive Australian Group of Eight universities. RESULTS:
      Applying elements of self-determination theory, external and introjected control
      loci (both strongly associated with alienation, disengagement and poor learning
      outcomes) were identified as common motivational determinants in this cohort.
      CONCLUSIONS: The importance of these findings to doctoral learning is discussed
      in light of previous research undertaken in higher education settings in the
      United States and the European Union. With motivation accepted as a malleable,
      context-sensitive factor, these data provide for both a better understanding of
      doctoral learning and highlight a potential avenue for future research aimed at
      improving outcomes and promoting meaningful learning processes in the biomedical
      doctorate.

PMID- 24571920
TI  - FGF1-mediated cardiomyocyte cell cycle reentry depends on the interaction of FGFR
      1 and Fn14.
AB  - Fibroblast growth factors (FGFs) signal through FGF receptors (FGFRs) mediating a
      broad range of cellular functions during embryonic development, as well as
      disease and regeneration during adulthood. Thus, it is important to understand
      the underlying molecular mechanisms that modulate this system. Here, we show that
      FGFR-1 can interact with the TNF receptor superfamily member fibroblast growth
      factor-inducible molecule 14 (Fn14) resulting in cardiomyocyte cell cycle
      reentry. FGF1-induced cell cycle reentry in neonatal cardiomyocytes could be
      blocked by Fn14 inhibition, while TWEAK-induced cell cycle activation was
      inhibited by blocking FGFR-1 signaling. In addition, costimulation experiments
      revealed a synergistic effect of FGF1 and TWEAK in regard to cardiomyocyte cell
      cycle induction via PI3K/Akt signaling. Overexpression of Fn14 with either FGFR-1
      long [FGFR-1(L)] or FGFR-1 short [FGFR-1(S)] isoforms resulted after FGF1/TWEAK
      stimulation in cell cycle reentry of >40% adult cardiomyocytes. Finally,
      coimmunoprecipitation and proximity ligation assays indicated that endogenous
      FGFR-1 and Fn14 interact with each other in cardiomyocytes. This interaction was
      strongly enhanced in the presence of their corresponding ligands, FGF1 and TWEAK.
      Taken together, our data suggest that FGFR-1/Fn14 interaction may represent a
      novel endogenous mechanism to modulate the action of these receptors and their
      ligands and to control cardiomyocyte cell cycle reentry.

PMID- 24571919
TI  - Genome-wide association mapping of acute lung injury in neonatal inbred mice.
AB  - Reactive oxygen species (ROS) contribute to the pathogenesis of many acute and
      chronic pulmonary disorders, including bronchopulmonary dysplasia (BPD), a
      respiratory condition that affects preterm infants. However, the mechanisms of
      susceptibility to oxidant stress in neonatal lungs are not completely understood.
      We evaluated the role of genetic background in response to oxidant stress in the
      neonatal lung by exposing mice from 36 inbred strains to hyperoxia (95% O2) for
      72 h after birth. Hyperoxia-induced lung injury was evaluated by using
      bronchoalveolar lavage fluid (BALF) analysis and pathology. Statistically
      significant interstrain variation was found for BALF inflammatory cells and
      protein (heritability estimates range: 33.6-55.7%). Genome-wide association
      mapping using injury phenotypes identified quantitative trait loci (QTLs) on
      chromosomes 1, 2, 4, 6, and 7. Comparative mapping of the chromosome 6 QTLs
      identified Chrm2 (cholinergic receptor, muscarinic 2, cardiac) as a candidate
      susceptibility gene, and mouse strains with a nonsynonymous coding single
      nucleotide polymorphism (SNP) in Chrm2 that causes an amino acid substitution
      (P265L) had significantly reduced hyperoxia-induced inflammation compared to
      strains without the SNP. Further, hyperoxia-induced lung injury was significantly
      reduced in neonatal mice with targeted deletion of Chrm2, relative to wild-type
      controls. This study has important implications for understanding the mechanisms
      of oxidative lung injury in neonates.

PMID- 24571921
TI  - A systems biology analysis of the unique and overlapping transcriptional
      responses to caloric restriction and dietary methionine restriction in rats.
AB  - Dietary methionine restriction (MR) and calorie restriction (CR) each improve
      metabolic health and extend life span. We used comprehensive transcriptome
      profiling and systems biology analysis to interrogate the unique and overlapping
      molecular responses in rats provided these dietary regimens for 20 mo after
      weaning. Microarray analysis was conducted on inguinal white adipose (IWAT),
      brown adipose tissue (BAT), liver, and skeletal muscle. Compared to controls, CR
      induced transcriptomic responses (absolute fold change >=1.5 and P<=0.05) were
      comparable in IWAT, BAT, and liver (~800 genes). MR-induced effects were largely
      restricted to IWAT and liver (~2400 genes). Pathway enrichment and gene
      coexpression analyses showed that induction of fatty acid synthesis in IWAT was
      common to CR and MR, whereas immunity and proinflammatory signaling pathways were
      specifically down-regulated in MR-treated IWAT and liver (FDR<=0.07-0.3). BAT
      demonstrated consistent down-regulation of PPAR-signaling under CR and MR,
      whereas muscle was largely unaffected. Interactome analysis identified CR
      specific down-regulation of cytoskeletal matrix components in IWAT and MR
      specific up-regulation of ribosomal genes in liver (FDR<=0.001). Transcriptomic
      down-regulation of inflammation genes by MR in IWAT was consistent with upstream
      inhibition of STAT3. Together, these results provide an integrated picture of the
      breadth of transcriptional responses to MR and CR among key metabolic tissues.

PMID- 24571922
TI  - Retinopathy in a novel model of metabolic syndrome and type 2 diabetes: new
      insight on the inflammatory paradigm.
AB  - The pathogenesis of diabetic retinopathy (DR) in metabolic syndrome (MetS) and
      type 2 diabetes (T2D) is not well studied, partly because an appropriate model
      has not been developed. Recently, we introduced a novel model of spontaneous T2D
      and MetS that replicates the relevant features of the human disease. In the
      current study, we investigated the retinal vascular changes in these animals.
      Experimental DR in streptozotocin (STZ)-injected rodents is described as an
      inflammatory disease, in which intercellular adhesion molecule 1 (ICAM-1) plays a
      key role. In comparison, advanced diabetes (HbA1c>10%) in the Nile grass rat
      (NGR) was associated with lower ICAM-1 protein expression when compared with that
      in normal or moderately diabetic animals. Vascular cell adhesion molecule 1 (VCAM
      1) expression, however, was unaffected by the disease state. As opposed to the
      STZ-induced model of DR, in diabetic NGRs, most leukocytes accumulated in the
      retinal arteries. Consistent with the ICAM-1 reduction, leukocyte accumulation
      was significantly reduced in advanced disease. Similarly, leukocyte adhesions
      were significantly lower, with elevated plasma triglycerides (>200 mg/dl), and
      cholesterol (>240 mg/dl). However, these adhesions were significantly higher in
      animals with higher plasma insulin (>5 MUIU/ml) and leptin (>20 ng/ml),
      suggesting a role for these hormones in diabetic retinal leukostasis. Diabetic
      NGRs showed substantial retinal endothelial injury, primarily in the
      microvessels, including vascular tortuosity, obliterated acellular capillaries,
      and pericyte ghosts. The NGR provides a convenient and realistic model for
      investigation of retinal changes in MetS/T2D with convincing advantages over the
      commonly used STZ-induced T1D.

PMID- 24571923
TI  - Association of lower limb muscle mass and energy expenditure with visceral fat
      mass in healthy men.
AB  - BACKGROUND: A high-calorie diet and physical inactivity, an imbalance between
      caloric intake and energy consumption, are major causes of metabolic syndrome
      (MetS), which manifests as accumulation of visceral fat and insulin resistance.
      However, the lifestyle-related factors associated with visceral fat mass in
      healthy men are not fully understood. METHODS: We evaluated visceral fat area
      (VFA), skeletal muscle mass, caloric intake, and energy expenditure in 67 healthy
      male participants (mean age, 36.9 +/- 8.8 years; body mass index 23.4 +/- 2.5
      kg/m2). RESULTS: Multiple regression analysis showed that the total skeletal
      muscle mass (P < 0.001) were negatively and age (P < 0.001) were positively
      associated with VFA. Lower limb muscle mass (P < 0.001) was strongly associated
      with VFA. However, total caloric intake, total energy expenditure, and energy
      expenditure during exercise were not associated with VFA. CONCLUSIONS: Skeletal
      muscle mass especially lower limb muscle mass negatively contributes to visceral
      fat mass in healthy men. Therefore, maintaining lower limb muscular fitness
      through daily activity may be a useful strategy for controlling visceral obesity
      and metabolic syndrome.

PMID- 24571924
TI  - Daily life impairments associated with childhood/adolescent attention
      deficit/hyperactivity disorder as recalled by adults: results from the European
      Lifetime Impairment Survey.
AB  - INTRODUCTION: The Lifetime Impairment Survey, conducted in Europe, assessed
      impairment and symptoms of attention-deficit/hyperactivity disorder (ADHD) in
      childhood, and experiences of ADHD diagnosis and treatment, as recalled by
      adults. METHODS: Adults with ADHD and without ADHD (control group) were invited
      to participate in an internet-based survey and report on their childhood
      experiences. History of ADHD diagnosis was self-reported. Groups were compared
      using impairment and symptom scales. RESULTS: Overall, 588 adults with ADHD and
      736 without ADHD participated. Mean (standard deviation [SD]) age at diagnosis of
      ADHD was 20.0 (12.6) years (median 18.0) following consultation with 3.8 (5.1)
      doctors (median 2) over 44.6 (69.3) months (median 17.0). A total of 64.1%
      (377/588) of adults with ADHD reported frustration or difficulties during the
      diagnostic process. The ADHD group had a higher mean (SD) score versus control
      for general (3.3 [1.2] vs 2.1 [1.2]; p < 0.001) and school impairment (2.8 [0.7]
      vs 2.3 [0.6]; p < 0.001) but not home impairment (2.1 [0.5] for both groups).
      Discussion The survey demonstrated that ADHD had a negative impact on all aspects
      of childhood investigated, as recalled by adults. CONCLUSIONS: These data provide
      insights into childhood impairments and identify areas for improvement in the
      management and treatment of ADHD.

PMID- 24571925
TI  - 2-Nitroimidazole-ruthenium polypyridyl complex as a new conjugate for cancer
      treatment and visualization.
AB  - A novel long-lifetime highly luminescent ruthenium polypyridyl complex containing
      2-nitroimidazole moiety [Ru(dip)2(bpy-2-nitroIm)]Cl2 (dip=4,7-diphenyl-1,10
      phenanthroline, bpy-2-nitroIm=4-[3-(2-nitro-1H-imidazol-1-yl)propyl]-2,2'
      bipyridine) has been designed cancer treatment and imaging. The luminescence
      properties of the synthesized compound strongly depend on the oxygen
      concentration. Under oxygen-free conditions quantum yield of luminescence and the
      average lifetime of emission were found to be 0.034 and 1.9 MUs, respectively,
      which is ca. three times higher in comparison to values obtained in air
      equilibrated solution. The binding properties of the investigated ruthenium
      complex to human serum albumin have been studied and the apparent binding
      constant for the formation of the protein-ruthenium adduct was determined to be
      1.1*10(5)M(-1). The quantum yield and the average lifetime of emission are
      greatly enhanced upon binding of ruthenium compound to the protein. The DNA
      binding studies revealed two distinguished binding modes which lead to a decrease
      in luminescence intensity of ruthenium complex up to 60% for [DNA]/[Ru]<2, and
      enhancement of emission for [DNA]/[Ru]>80. Preliminary biological studies
      confirmed fast and efficient accumulation of the ruthenium complex inside cells.
      Furthermore, the ruthenium complex was found to be relatively cytotoxic with LD50
      of 12 and 13 MUM for A549 and CT26 cell lines, respectively, under normoxic
      conditions. The retention and cellular uptake of ruthenium complex is enhanced
      under hypoxic conditions and its LD50 decreases to 8 MUM for A549 cell line.

PMID- 24571927
TI  - Children's vocabulary growth in English and Spanish across early development and
      associations with school readiness skills.
AB  - In line with evidence that variation in children's vocabulary size facilitates
      learning, we asked whether growth in Mexican and Dominican children's expressive
      vocabularies in English and/or Spanish would predict later cognitive skills.
      Children and mothers were video-recorded sharing wordless books at 2, 3, 4, and 5
      years, and children were assessed on language, literacy, and math skills at 5
      years. Growth in children's English and Spanish vocabularies, based on
      transcriptions of booksharing interactions, predicted specific cognitive skills
      and was associated with changes to mothers' language use across time. Mothers'
      years in the United States predicted children's English vocabulary growth. 

PMID- 24571928
TI  - Numerical abilities in children with congenital hemiplegia: an investigation of
      the role of finger use in number processing.
AB  - In this study, we assessed basic and more complex non-symbolic and symbolic
      numerical task abilities in children with hemiplegia and obtained a detailed
      picture of their strengths and weaknesses in the numerical domain. Those
      children, who experience difficulties in finger gnosia and spontaneous use of
      fingers in counting, exhibit difficulties in finger pattern recognition and
      symbolic numerical tasks. However, their non-symbolic numerical abilities and
      arithmetic skills are preserved. These original results are discussed in light of
      the "manumerical cognition" hypothesis, which postulates that the use of fingers
      in numerical activities during childhood shapes our comprehension of numbers. 

PMID- 24571926
TI  - Metabolic adaptation to weight loss: implications for the athlete.
AB  - Optimized body composition provides a competitive advantage in a variety of
      sports. Weight reduction is common among athletes aiming to improve their
      strength-to-mass ratio, locomotive efficiency, or aesthetic appearance. Energy
      restriction is accompanied by changes in circulating hormones, mitochondrial
      efficiency, and energy expenditure that serve to minimize the energy deficit,
      attenuate weight loss, and promote weight regain. The current article reviews the
      metabolic adaptations observed with weight reduction and provides recommendations
      for successful weight reduction and long term reduced-weight maintenance in
      athletes. 

PMID- 24571929
TI  - Visuomotor function in children treated for acute lymphoblastic leukaemia with
      chemotherapy only.
AB  - This study aimed to evaluate visuomotor function in children treated for acute
      lymphoblastic leukaemia (ALL). The performance of 64 children, 1-7 years post
      chemotherapy for ALL, was compared to that of their healthy peers (n = 56) on
      visuomotor integration (VMI) and motor coordination (MC) tasks. Children
      posttreatment for ALL displayed significantly reduced VMI, but not MC,
      performances as compared to controls. Children treated on chemotherapy-only ALL
      regimes are at heightened risk for visuomotor integration deficits. Monitoring of
      visuomotor skills and implementation of appropriate interventions targeting
      higher level visuomotor integration skills should form an important component of
      any ALL long-term effects program. 

PMID- 24571930
TI  - The effects of visual distracter complexity on auditory evoked p3b in contact
      sports athletes.
AB  - "Classic" P3b auditory oddball paradigms are insensitive to subtle deficits. An
      auditory oddball paradigm paired with visual distracters was used to compare
      football players with history of concussion, football players without history of
      concussion, and non-contact sport athletes. As hypothesized, increasing
      complexity of, and attention to, visual distracters reduced P3b amplitude. P3b
      amplitudes from non-contact athletes were larger than those from football
      players; however, players with and without a history of concussion were not
      significantly different. An auditory oddball paradigm with simple visual
      distracter improves sensitivity to cognitive deficits. Subconcussive impacts may
      contribute to brain damage frequently attributed to concussions. 

PMID- 24571931
TI  - A review of cognitive outcomes in children following perinatal stroke.
AB  - Perinatal stroke is a significant cause of congenital neurological disability.
      Although motor deficits and epilepsy are relatively easy to identify,
      developmental and behavioral co-morbidities are more complex and challenging to
      define. We provide an overview of perinatal stroke syndromes and theories
      relating injury in the developing brain to long-term outcomes. We present a
      comprehensive overview of the effects on intelligence and other specific
      cognitive domains, as well as investigations relating clinical features and
      neuroimaging to deficits. Better understanding of the impact of early stroke has
      potential to elucidate processes of brain development, in addition to providing
      guidance for prognosis and rehabilitation. 

PMID- 24571933
TI  - UV-driven microvalve based on a micro-nano TiO2/SiO2 composite surface for
      microscale flow control.
AB  - This paper presents a novel ultraviolet (UV)-driven microvalve based on the
      concept of inserting a trimethyl chlorosilane (CTMS) modified TiO2/SiO2 composite
      patch of switchable wettability in a microfluidic system. A unique micro-nano
      hierarchical structure was designed and used to enhance the overall wetting
      contrast with the aim of improving the wetting-based valve performances. Field
      emission scanning electron microscopy (FE-SEM) and x-ray photoelectron
      spectroscopy (XPS) were used to characterize the morphology and chemical
      composition of the surface. UV-driven wettability conversion on the patched
      microchannel was investigated using water column relative height tests, and the
      results confirmed the significant improvement of the hierarchical structure with
      the surface hydrophobic/hydrophilic conversion, which produced enhancements of
      276% and 95% of the water-repellent and water-sucking pressures, respectively,
      compared with those of the single-scale TiO2 nanopatterned structure.
      Accordingly, a good reversible and repeated on-off performance was identified by
      the valve tests, highlighting the potential application of the novel microvalve
      in the efficient control of microscale flow.

PMID- 24571932
TI  - A randomised controlled trial and cost-effectiveness evaluation of 'booster'
      interventions to sustain increases in physical activity in middle-aged adults in
      deprived urban neighbourhoods.
AB  - BACKGROUND: More evidence is needed on the potential role of 'booster'
      interventions in the maintenance of increases in physical activity levels after a
      brief intervention in relatively sedentary populations. OBJECTIVES: To determine
      whether objectively measured physical activity, 6 months after a brief
      intervention, is increased in those receiving physical activity 'booster'
      consultations delivered in a motivational interviewing (MI) style, either face to
      face or by telephone. DESIGN: Three-arm, parallel-group, pragmatic, superiority
      randomised controlled trial with nested qualitative research fidelity and
      geographical information systems and health economic substudies. Treatment
      allocation was carried out using a web-based simple randomisation procedure with
      equal allocation probabilities. Principal investigators and study statisticians
      were blinded to treatment allocation until after the final analysis only.
      SETTING: Deprived areas of Sheffield, UK. PARTICIPANTS: Previously sedentary
      people, aged 40-64 years, living in deprived areas of Sheffield, UK, who had
      increased their physical activity levels after receiving a brief intervention.
      INTERVENTIONS: Participants were randomised to the control group (no further
      intervention) or to two sessions of MI, either face to face ('full booster') or
      by telephone ('mini booster'). Sessions were delivered 1 and 2 months post
      randomisation. MAIN OUTCOME MEASURES: The primary outcome was total energy
      expenditure (TEE) per day in kcal from 7-day accelerometry, measured using an
      Actiheart device (CamNtech Ltd, Cambridge, UK). Independent evaluation of
      practitioner competence was carried out using the Motivational Interviewing
      Treatment Integrity assessment. An estimate of the per-participant intervention
      costs, resource use data collected by questionnaire and health-related quality of
      life data were analysed to produce a range of economic models from a short-term
      NHS perspective. An additional series of models were developed that used TEE
      values to estimate the long-term cost-effectiveness. RESULTS: In total, 282
      people were randomised (control = 96; mini booster = 92, full booster = 94) of
      whom 160 had a minimum of 4 out of 7 days' accelerometry data at 3 months
      (control = 61, mini booster = 47, full booster = 52). The mean difference in TEE
      per day between baseline and 3 months favoured the control arm over the combined
      booster arm but this was not statistically significant (-39 kcal, 95% confidence
      interval -173 to 95, p = 0.57). The autonomy-enabled MI communication style was
      generally acceptable, although some participants wanted a more paternalistic
      approach and most expressed enthusiasm for monitoring and feedback components of
      the intervention and research. Full boosters were more popular than mini
      boosters. Practitioners achieved and maintained a consistent level of MI
      competence. Walking distance to the nearest municipal green space or leisure
      facilities was not associated with physical activity levels. Two alternative
      modelling approaches both suggested that neither intervention was likely to be
      cost-effective. CONCLUSIONS: Although some individuals do find a community-based,
      brief MI 'booster' intervention supportive, the low levels of recruitment and
      retention and the lack of impact on objectively measured physical activity levels
      in those with adequate outcome data suggest that it is unlikely to represent a
      clinically effective or cost-effective intervention for the maintenance of
      recently acquired physical activity increases in deprived middle-aged urban
      populations. Future research with middle-aged and relatively deprived populations
      should explore interventions to promote physical activity that require less
      proactive engagement from individuals, including environmental interventions.
      STUDY REGISTRATION: Current Controlled Trials ISRCTN56495859, ClinicalTrials.gov
      NCT00836459. FUNDING: This project was funded by the NIHR Health Technology
      Assessment programme and will be published in full in Health Technology
      Assessment; Vol. 18, No. 13. See the NIHR Journals Library website for further
      project information.

PMID- 24571934
TI  - Primary Multifocal Pleomorphic Adenoma of the Parotid Gland with Dermal
      Involvement.

PMID- 24571935
TI  - Does STN-DBS really not change emotion recognition in Parkinson's disease?

PMID- 24571939
TI  - Computed tomography evaluation of aortic remodeling after endovascular treatment
      for complicated ulcer-like projection in patients with type B aortic intramural
      hematoma.
AB  - OBJECTIVE: The purpose was to investigate changes of the affected aorta after
      endovascular treatment for complicated ulcer-like projection (ULP), including
      aneurysmal change or rupture of ULP, or both, in patients with type B aortic
      intramural hematoma (IMH). METHODS: The study evaluated 18 patients (nine men)
      undergoing thoracic endovascular aortic repair for progressive aneurysmal
      formation of ULP (n = 17), rupture of ULP (n = 5), or both. Patients were a
      median age of 72 years (range, 45-83 years). Regular follow-up computed
      tomography studies were performed after treatment (mean follow-up, 61.2 months).
      A workstation was used to calculate changes on computed tomography images in the
      size or volume of ULP, affected aorta, and IMH. The growth rate of the volume of
      the affected aorta and IMH was also calculated before and after treatment. We
      evaluated the data using the paired t-test. RESULTS: A stent graft was
      successfully deployed and ULPs disappeared in all patients. IMH disappeared in 16
      or decreased in two after treatment. There were significant differences in the
      mean maximum aortic diameter (37.8 +/- 5.2 vs 34.5 +/- 5.2 mm; P = .0006), mean
      IMH volume (39.4 +/- 12.1 vs 2.0 +/- 6.0 mL; P < .0001), and total volume of the
      aorta with IMH (158.1 +/- 40.2 vs 128.9 +/- 28.0 mL; P < .0001) before and after
      treatment. CONCLUSIONS: Endovascular treatment is a useful treatment for
      complicated ULP in patients with IMH. Endovascular treatment also contributes to
      ideal remodeling of the affected aorta.

PMID- 24571937
TI  - Pathology-specific secondary aortic interventions after thoracic endovascular
      aortic repair.
AB  - OBJECTIVE: Despite improved short-term outcomes, concerns remain regarding
      durability of thoracic endovascular aortic repair (TEVAR). The purpose of this
      analysis was to evaluate the pathology-specific incidence of secondary aortic
      interventions (SAI) after TEVAR and their impact on survival. METHODS:
      Retrospective review was performed of all TEVAR procedures and SAI at one
      institution from 2004-2011. Kaplan-Meier analysis was used to estimate survival.
      RESULTS: Of 585 patients, 72 (12%) required SAI at a median of 5.6 months
      (interquartile range, 1.4-14.2) with 22 (3.7%) requiring multiple SAI. SAI
      incidence differed significantly by pathology (P = .002) [acute dissection
      (21.3%), postsurgical (20.0%), chronic dissection (16.7%), degenerative aneurysm
      (10.8%), traumatic transection (8.1%), penetrating ulcer (1.5%), and other
      etiologies (14.8%)]. Most common indications after dissection were persistent
      false lumen flow and proximal/distal extension of disease. For degenerative
      aneurysms, SAI was performed primarily to treat type I/III endoleaks. SAI
      patients had a greater mean number of comorbidities (P < .0005), stents placed (P
      = .0002), and postoperative complications after the index TEVAR (P < .0005)
      compared with those without SAI. Freedom from SAI at 1 and 5 years (95%
      confidence interval) was estimated to be 86% (82%-90%) and 68% (57%-76%),
      respectively. There were no differences in survival (95% confidence interval)
      between patients requiring SAI and those who did not [SAI 1-year, 88% (77%-93%);
      5-year, 51% (37%-63%); and no SAI 1-year, 82% (79%-85%); 5-year, 67% (62%-71%)
      (log-rank, P = .2)]. CONCLUSIONS: SAI after TEVAR is not uncommon, particularly
      in patients with dissection, but does not affect long-term survival. Aortic
      pathology is the most important variable impacting survival and dictated need,
      timing, and mode of SAI. The varying incidence of SAI by indication underscores
      the need for diligent surveillance protocols that should be pathology-specific.

PMID- 24571938
TI  - Outcomes of open and endovascular repair for ruptured and nonruptured internal
      iliac artery aneurysms.
AB  - OBJECTIVE: To evaluate outcomes of open (OR) and endovascular repair (II-EVAR) of
      internal iliac artery aneurysms (IIAAs) with or without preservation of internal
      iliac artery (IIA) flow. METHODS: We reviewed the clinical data of consecutive
      patients treated for IIAAs between 2001 and 2012. End-points were morbidity,
      mortality, graft patency, and freedom from pelvic ischemic symptoms (buttock
      claudication, ischemic colitis, and spinal cord injury). RESULTS: There were 97
      patients, 87 male and 10 female, with mean age of 74 +/- 8 years. A total of 125
      IIAAs (71 unilateral and 27 bilateral) with mean diameter of 3.6 +/- 2 cm were
      treated. Eighty-two patients (86%) had elective repair and 15 (14%) required
      emergent repair (mean size, 6.7 +/- 2.4 cm; range, 3.6-10 cm). OR in 60 patients
      (62%; 49 elective, 11 emergent) included IIA bypass in 36 (60%) patients and
      endoaneurysmorrhaphy in 24 (40%). II-EVAR in 37 patients (38%; 30 elective, 4
      emergent) required IIA embolization in 29, iliac branch device in five or open
      IIA bypass in three, combined with bifurcated aortic stent grafts in 17. Early
      mortality was 1% for elective (1/49 open, 0/33 endovascular) and 7% for emergent
      repair (1/11 open, 0/4 endovascular). Early morbidity (43% vs 8%; P < .001) and
      length of stay (9 vs 1 day; P < .001) were significantly higher for OR as
      compared with II-EVAR. Pelvic ischemic complications occurred in 25 patients
      (26%), including hip claudication in 23, ischemic colitis in two, and paraplegia
      in one. Freedom from buttock claudication at 2 years was 25% in patients with no
      IIA preserved, 68% with preservation of one, and 95% with preservation of both
      IIAs (P = .002). Freedom from buttock claudication was higher after OR than after
      II-EVAR (79% vs 59%; P = .05). Primary and secondary patency rates of IIAA
      bypasses were 95%, and 80% at 1 and 3 years, respectively. CONCLUSIONS: II-EVAR
      of IIAAs is associated with fewer complications and shorter hospital stay
      compared with OR. Open and endovascular IIA reconstructions have very good long
      term patency, and preservation of IIA flow is associated with higher freedom from
      buttock claudication.

PMID- 24571942
TI  - Popliteal artery pseudoaneurysm associated with osteochondroma.

PMID- 24571941
TI  - Intravascular ultrasound as a clinical adjunct for carotid plaque
      characterization.
AB  - OBJECTIVE: Virtual histology intravascular ultrasound (VH IVUS) is valuable for
      estimating minimal lumen diameter and plaque characterization. The clinical use
      of IVUS in carotid intervention is not well characterized. We aim to evaluate the
      role of IVUS in carotid plaque characterization and determine whether it could be
      predictive of procedure-related microemboli. METHODS: From July 2010, patients
      with severe carotid stenosis who underwent elective carotid stenting procedures
      were prospectively enrolled. IVUS evaluation was performed before stent
      placement. Patient demographics, comorbidities, and preoperative images were
      recorded. Comparison of pre- and postoperative diffusion-weighted magnetic
      resonance images was used to identify the number of procedure-related
      microemboli. IVUS-derived minimal lumen diameter and vessel wall plaque
      characteristics were collected. Univariate and multivariate logistic regressions
      were used to search for associations between IVUS-derived VH data and incidence
      of microemboli. RESULTS: A total of 38 high-risk patients receiving carotid
      stenting were enrolled. Among them, 25 patients had type I aortic arches and 17
      of the patients were symptomatic (preoperative stroke or transient ischemic
      attack). VH IVUS data did not show strong associations with microemboli, however,
      a trend was found between the area of fibrous tissue and median or more incidence
      of microemboli (P = .099). IVUS-defined vessel diameter maximum was associated
      with median or more incidence of microemboli (P = .042). In addition, median or
      more incidence of microemboli showed trends with proximal common carotid artery
      calcification (P = .056) and with being over the age of 80 (P = .06).
      Contralateral carotid occlusion or high-grade stenosis was associated with
      postoperative contralateral microemboli (P = .036). CONCLUSIONS: We demonstrate
      that periprocedural carotid IVUS is clinically feasible. VH IVUS may be helpful
      in better understanding plaque morphology and determining optimal stent
      placement. However, its use in predicting microembolization remains limited.

PMID- 24571940
TI  - Neutrophil-lymphocyte ratio as a predictor of cognitive dysfunction in carotid
      endarterectomy patients.
AB  - BACKGROUND: Systemic inflammation has been implicated in the development of
      cognitive dysfunction following carotid endarterectomy (CEA). Neutrophil
      lymphocyte ratio (NLR) is a reliable measure of systemic inflammation. We
      hypothesize that patients with elevated preoperative NLR have increased risk of
      cognitive dysfunction 1 day after CEA. METHODS: Five hundred fifty-one patients
      scheduled for CEA were enrolled at Columbia University in New York, NY from 1995
      to 2012. NLR was retrospectively reviewed; only 432 patients had preoperative NLR
      values available within 2 weeks of CEA. NLR was analyzed as a continuous variable
      and categorically with a cutoff of >=5 and <5 and equal tertiles, as done in
      previous studies. RESULTS: Patients with cognitive dysfunction had significantly
      higher NLR than those without cognitive dysfunction (4.5 +/- 4.0 vs 3.2 +/- 2.6;
      P < .001). The incidence of cognitive dysfunction was significantly higher in
      patients with NLR >=5 than NLR <5 (34.7% vs 12.8%; P < .001). Significantly fewer
      patients in the low tertile had cognitive dysfunction than in the high tertile
      (6.9% vs 25.9%; P <.001) and middle tertile (6.9% vs 17.4%; P = .006). In the
      final multivariate model, diabetes mellitus (odds ratio [OR], 2.03; 95%
      confidence interval [CI], 1.08-3.75; P = .03) and NLR >=5 (OR, 3.38; 95% CI, 1.81
      6.27; P < .001) were significantly associated with higher odds of cognitive
      dysfunction, while statin use was significantly associated with lower odds (OR,
      0.48; 95% CI, 0.27-0.84; P = .01). CONCLUSIONS: Preoperative NLR is associated
      with cognitive dysfunction 1 day after CEA. NLR >=5 and diabetes mellitus are
      significantly associated with increased odds of cognitive dysfunction whereas
      statin use is significantly associated with decreased odds.

PMID- 24571943
TI  - Giant aneurysm of the abdominal aorta.

PMID- 24571944
TI  - Double-barreled cannon stenting for extremely dilated landing zone in a giant
      thoracoabdominal aneurysm.

PMID- 24571945
TI  - Unknown pages in the history of vascular stent grafting.

PMID- 24571946
TI  - Outcomes of open and endovascular repair for ruptured and nonruptured internal
      iliac artery aneurysms.

PMID- 24571947
TI  - Regarding "Management strategy for spontaneous isolated dissection of the
      superior mesenteric artery based on morphologic classification".

PMID- 24571948
TI  - Reply: To PMID 23932803.

PMID- 24571949
TI  - Regarding "Statin use and lower extremity amputation risk in nonelderly diabetic
      patients".

PMID- 24571950
TI  - Regarding "One-year outcomes from an international study of the Ovation abdominal
      stent graft system for endovascular aneurysm repair".

PMID- 24571951
TI  - Reply: To PMID 23978572.

PMID- 24571952
TI  - Supporting patients treated for prostate cancer: a video vignette study with an
      email-based educational program in general practice.
AB  - BACKGROUND: Men who have been treated for prostate cancer in Australia can
      consult their general practitioner (GP) for advice about symptoms or side effects
      at any time following treatment. However, there is no evidence that such men are
      consistently advised by GPs and patients experience substantial unmet need for
      reassurance and advice. OBJECTIVE: The intent of the study was to evaluate a
      brief, email-based educational program for GPs to manage standardized patients
      presenting with symptoms or side effects months or years after prostate cancer
      treatment. METHODS: GPs viewed six pairs of video vignettes of actor-patients
      depicting men who had been treated for prostate cancer. The actor-patients
      presented problems that were attributable to the treatment of cancer. In Phase 1,
      GPs indicated their diagnosis and stated if they would prescribe, refer, or order
      tests based on that diagnosis. These responses were compared to the management
      decisions for those vignettes as recommended by a team of experts in prostate
      cancer. After Phase 1, all the GPs were invited to participate in an email-based
      education program (Spaced Education) focused on prostate cancer. Participants
      received feedback and could compare their progress and their performance with
      other participants in the study. In Phase 2, all GPs, regardless of whether they
      had completed the program, were invited to view another set of six video
      vignettes with men presenting similar problems to Phase 1. They again offered a
      diagnosis and stated if they would prescribe, refer, or order tests based on that
      diagnosis. RESULTS: In total, 64 general practitioners participated in the
      project, 57 GPs participated in Phase 1, and 45 in Phase 2. The Phase 1 education
      program was completed by 38 of the 57 (59%) participants. There were no
      significant differences in demographics between those who completed the program
      and those who did not. Factors determining whether management of cases was
      consistent with expert opinion were number of sessions worked per week (OR 0.78,
      95% CI 0.67-0.90), site of clinical practice (remote practice, OR 2.25, 95% CI
      1.01-5.03), number of patients seen per week (150 patients or more per week, OR
      10.66, 95% CI 3.40-33.48), and type of case viewed. Completion of the Spaced
      Education did impact whether patient management was consistent with expert
      opinion (not completed, OR 0.88, 95% CI 0.5-1.56). CONCLUSIONS: The management of
      standardized patients by GPs was particularly unlikely to be consistent with
      expert opinion in the management of impotence and bony metastasis. There was no
      evidence from this standardized patient study that Spaced Education had an impact
      on the management of patients in this context. However, the program was not
      completed by all participants. Practitioners with a greater clinical load were
      more likely to manage cases as per expert opinion.

PMID- 24571953
TI  - The effect of age on sagittal plane profile of the lumbar spine according to
      standing, supine, and various sitting positions.
AB  - BACKGROUND: The sagittal alignment of the spine changes depending on body posture
      and degenerative changes. This study aimed to observe changes in sagittal
      alignment of the lumbar spine with different positions (standing, supine, and
      various sitting postures) and to verify the effect of aging on lumbar sagittal
      alignment. METHODS: Whole-spine lateral radiographs were obtained for young
      volunteers (25.4 +/- 2.3 years) and elderly volunteers (66.7 +/- 1.7 years).
      Radiographs were obtained in standing, supine, and sitting (30 degrees , 60
      degrees , and 90 degrees ) positions respectively. We compared the radiological
      changes in the lordotic and segmental angles in different body positions and at
      different ages. Upper and lower lumbar lordosis were defined according to
      differences in anatomical sagittal mobility and kinematic behavior. RESULTS:
      Lumbar lordosis was greater in a standing position (52.79 degrees  and 53.90
      degrees  in young and old groups, respectively) and tended to decrease as
      position changed from supine to sitting. Compared with the younger group, the
      older group showed significantly more lumbar lordosis in supine and 60 degrees 
      and 90 degrees  sitting positions (P=0.043, 0.002, 0.011). Upper lumbar lordosis
      in the younger group changed dynamically in all changed positions compared with
      the old group (P=0.019). Lower lumbar lordosis showed a decreasing pattern in
      both age groups, significantly changing as position changed from 30 degrees  to
      60 degrees  (P=0.007, 0.007). CONCLUSIONS: Lumbar lordosis decreases as position
      changes from standing to 90 degrees sitting. The upper lumbar spine is more
      flexible in individuals in their twenties compared to those in their sixties.
      Changes in lumbar lordosis were concentrated in the lower lumbar region in the
      older group in sitting positions.

PMID- 24571954
TI  - Immune-inflammatory markers and arterial stiffness indexes in subjects with acute
      ischemic stroke with and without metabolic syndrome.
AB  - OBJECTIVE: The aim of our study was to evaluate the associations between arterial
      stiffness indexes and immune-inflammatory markers in subjects with acute ischemic
      stroke with and without metabolic syndrome. MATERIALS/METHODS: We enrolled 130
      patients with acute ischemic stroke and metabolic syndrome, 127 patients with
      acute ischemic stroke without metabolic syndrome and 120 control subjects without
      acute stroke. Applanation tonometry was used to record the augmentation index
      (Aix) and pulse wave velocity (PWV). We also evaluated plasma levels of C
      reactive protein (CRP), Interleukin-1beta (IL-1beta), tumor necrosis factor-alpha
      (TNF-alpha), Interleukin-6 (IL-6) and Interleukin-10 (IL-10), E-selectin, P
      selectin, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion
      molecule-1 (VCAM-1), von Willebrand Factor (vWF) plasma levels, tissue
      plasminogen activator (TPA) and plasminogen activator inhibitor-1 (PAI-1).
      RESULTS: In subjects with acute ischemic stroke and metabolic syndrome we
      observed higher median plasma values of immuno-inflammatory markers. In acute
      ischemic stroke patients and metabolic syndrome in relation of each TOAST subtype
      we observed a more significant positive correlation between PWV and immuno
      inflammatory markers. CONCLUSIONS: Stroke subjects with acute ischemic stroke and
      metabolic syndrome showed a higher degree of immuno-inflammatory and arterial
      stiffness indexes possibly due to metabolic background of these types of patients
      that trigger a more intense immune-inflammatory activation irrespective of stroke
      subtype, whereas being related to stroke subtype in subjects without metabolic
      syndrome.

PMID- 24571955
TI  - Conscientious objection to referrals for abortion: pragmatic solution or threat
      to women's rights?
AB  - BACKGROUND: Conscientious objection has spurred impassioned debate in many
      Western countries. Some Norwegian general practitioners (GPs) refuse to refer for
      abortion. Little is know about how the GPs carry out their refusals in practice,
      how they perceive their refusal to fit with their role as professionals, and how
      refusals impact patients. Empirical data can inform subsequent normative
      analysis. METHODS: Qualitative research interviews were conducted with seven GPs,
      all Christians. Transcripts were analysed using systematic text condensation.
      RESULTS: Informants displayed a marked ambivalence towards their own refusal
      practices. Five main topics emerged in the interviews: 1) carrying out
      conscientious objection in practice, 2) justification for conscientious
      objection, 3) challenges when relating to colleagues, 4) ambivalence and
      consistency, 5) effects on the doctor-patient relationship. CONCLUSIONS:
      Norwegian GP conscientious objectors were given to consider both pros and cons
      when evaluating their refusal practices. They had settled on a practical
      compromise, the precise form of which would vary, and which was deemed an
      acceptable middle way between competing interests.

PMID- 24571956
TI  - Reduced temperature-dependent thermal conductivity of magnetite thin films by
      controlling film thickness.
AB  - We report on the out-of-plane thermal conductivities of epitaxial Fe3O4 thin
      films with thicknesses of 100, 300, and 400 nm, prepared using pulsed laser
      deposition (PLD) on SiO2/Si substrates. The four-point probe three-omega (3
      omega) method was used for thermal conductivity measurements of the Fe3O4 thin
      films in the temperature range of 20 to 300 K. By measuring the temperature
      dependent thermal characteristics of the Fe3O4 thin films, we realized that their
      thermal conductivities significantly decreased with decreasing grain size and
      thickness of the films. The out-of-plane thermal conductivities of the Fe3O4
      films were found to be in the range of 0.52 to 3.51 W/m . K at 300 K. For 100-nm
      film, we found that the thermal conductivity was as low as approximately 0.52 W/m
      . K, which was 1.7 to 11.5 order of magnitude lower than the thermal conductivity
      of bulk material at 300 K. Furthermore, we calculated the temperature dependence
      of the thermal conductivity of these Fe3O4 films using a simple theoretical
      Callaway model for comparison with the experimental data. We found that the
      Callaway model predictions agree reasonably with the experimental data. We then
      noticed that the thin film-based oxide materials could be efficient
      thermoelectric materials to achieve high performance in thermoelectric devices. 

PMID- 24571957
TI  - Development of oral motor behavior related to the skill assisted spoon feeding.
AB  - Milestones in the typical development of eating skills are considered to be
      nippling (breast or bottle), eating from a spoon, drinking from a cup, biting and
      chewing. The purpose of this research was to study the development and
      consolidation of oral motor behavior related to the skill assisted spoon feeding
      in young infants. The present study longitudinally investigated the development
      of this skill in 39 healthy children from the start of spoon feeding until the
      skill was acquired. The Observation List Spoon Feeding with 7 observation items
      for oral motor behavior and 6 items for abnormal behavior was used. Results
      showed that infants between 4 and 8 months of age needed 5.7 weeks (SD 2.1), with
      a range of 8 weeks (from 2 to 10 weeks) to acquire this skill. No significant
      correlation (p=.109) between age at start spoon feeding and weeks needed to
      develop the skill was found. During this period oral motor behavior consolidated
      and abnormal behavior diminished. With this study it is shown that the period in
      weeks needed to acquire the oral motor behavior for the skill assisted spoon
      feeding is important in case of feeding problems.

PMID- 24571958
TI  - One-pot synthesis of gold nanorods using binary surfactant systems with improved
      monodispersity, dimensional tunability and plasmon resonance scattering
      properties.
AB  - A facile seedless growth method for high-yield synthesis of monodisperse gold
      nanorods using binary surfactant mixtures is reported for the first time. In
      comparison with other seedless methods, the present method enables the
      preparation of gold nanorods with much better monodispersity. Moreover, the
      present seedless growth method enables the preparation of not only thin gold
      nanorods but also thick gold nanorods which cannot be prepared by other reported
      seedless methods. Dark-field microscopy measurements of a single gold nanorod
      indicate that the thicker gold nanorod shows enhanced scattering properties. 

PMID- 24571960
TI  - Moving beyond the headlines: improving the technical quality of radical
      prostatectomy.
AB  - Recent work from surgeons in Europe and the United States has provided both the
      motivation, and a blueprint, for implementing peer assessments of technical skill
      as a robust and practical strategy for evaluating and ultimately improving
      technical expertise with radical prostatectomy. 

PMID- 24571959
TI  - Long-term outcomes of salvage lymph node dissection for clinically recurrent
      prostate cancer: results of a single-institution series with a minimum follow-up
      of 5 years.
AB  - BACKGROUND: Prostate cancer (PCa) patients with lymph node recurrence after
      radical prostatectomy (RP) are usually managed with androgen-deprivation therapy.
      Despite the absence of prospective randomized studies, salvage lymph node
      dissection (LND) has been proposed as an alternative treatment option. OBJECTIVE:
      To examine long-term outcomes of salvage LND in patients with nodal recurrent PCa
      documented by 11C-choline positron emission tomography/computed tomography
      (PET/CT) scan. DESIGN, SETTING, AND PARTICIPANTS: Overall, 59 patients affected
      by biochemical recurrence (BCR) with 11C-choline PET/CT scan with pathologic
      activity treated between 2002 and 2008 were included. INTERVENTION: Pelvic and/or
      retroperitoneal salvage LND. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSES:
      Biochemical response (BR) was defined as prostate-specific antigen (PSA) <0.2
      ng/ml at 40 d after surgery. BCR for those who achieved BR was defined as a PSA
      >0.2 ng/ml. Clinical recurrence (CR) was defined as a positive PET/CT scan after
      salvage LND in the presence of a rising PSA. Kaplan-Meier curves assessed time to
      BCR, CR, and cancer-specific mortality (CSM). Cox regression analyses were fitted
      to assess predictors of CR. RESULTS AND LIMITATIONS: Median follow-up after
      salvage LND was 81.1 mo. Overall, 35 patients (59.3%) achieved BR. The 8-yr BCR
      free survival rate in patients with complete BR was 23%. Overall, the 8-yr CR-
      and CSM-free survival rates were 38% and 81%, respectively. In multivariable
      analyses evaluating preoperative variables, PSA at salvage LND represented the
      only predictor of CR (p=0.03). When postoperative variables were considered, BR
      and the presence of retroperitoneal lymph node metastases were significantly
      associated with the risk of CR (all p <= 0.04). Our study is limited by the lack
      of a control group. CONCLUSIONS: Salvage LND may represent a therapeutic option
      for patients with BCR after RP and nodal pathologic uptake at 11C-choline PET/CT
      scan. Although most patients progressed to BCR after salvage LND, roughly 40% of
      them experienced CR-free survival. PATIENT SUMMARY: Salvage lymph node dissection
      may represent a therapeutic option for selected patients with nodal recurrence
      after radical prostatectomy. Roughly 40% of men did not show any further clinical
      recurrence at long-term follow-up after surgery.

PMID- 24571961
TI  - Team consultancy using cognitive analytic therapy: a controlled study in
      assertive outreach.
AB  - The objective of this study was to evaluate the clinical and organizational
      efficacy of formulation-based consultancy to clinical teams using a randomized
      control trial methodology. Patients in an Assertive Outreach Team (AOT) were
      randomized into cognitive analytic consultancy (CAC; n = 10) or treatment as
      usual (TAU; n = 10). CAC consisted of three consultancy sessions with individual
      team members to formulate and map the dysfunctional roles and procedures adopted
      by both patient and team. Subsequent changes to practice were then supported via
      team supervision. Measures of patient and team functioning were taken across four
      discrete study phases; (1) baseline team training, (2) case consultation, (3)
      team supervision and (4) 3-month follow-up. Team members were additionally
      interviewed before and following the trial. No differences were evident between
      CAC and TAU in terms of patient outcomes. However, the climate of the AOT
      significantly improved longitudinally over the course of the trial, with CAC
      facilitating enhanced clinical and team practices. The results are discussed in
      terms of methodological limitations, the advantages/disadvantages of team
      consultation and the potential for the further development of the CAC model.

PMID- 24571962
TI  - Neurobiological correlates of social anxiety disorder: an update.
AB  - Social anxiety disorder (SAD) is a condition characterized by pervasiveness and
      impairment in social functioning, with a prevalence in the general population
      between 1.9% and 12.1%. The most consistent findings on its neurobiological
      underpinnings involve a wide range of neurotransmitters (serotonin,
      norepinephrine, glutamate, and GABA) and neuropeptides (oxytocin), but no
      comprehensive hypothesis is yet available. In particular, oxytocin is becoming
      increasingly established as a "prosocial neuropeptide" and, as such, is a major
      focus of current research, with a great range of therapeutic applications
      including SAD treatment. Specifically, the amygdala plays a pivotal role in
      conditioning and processing of fear, and exaggerated amygdala responses in SAD
      patients have been observed during various social-emotional stimuli. In addition
      to the amygdala, other brain areas of interest in SAD-related circuitry are
      represented by the medial prefrontal cortex, dorsal raphe, striatum, locus
      coeruleus, prefrontal cortex, insular cortex, and anterior cingulate cortex. The
      aim of this review is to provide an update on neurobiological correlates of SAD,
      with a special focus on neurotransmitters and brain areas possibly involved, and
      suggestions for future research that could lead to more specific therapeutic
      interventions. 

PMID- 24571963
TI  - A systematic review of web-based educational interventions.
AB  - A complement to in-hospital educational interventions is web-based patient
      education accessed during the home recovery period. While findings demonstrate
      the effectiveness of web-based patient education interventions on patient
      outcomes, they fall short of identifying the characteristics that are associated
      with desired outcomes. The purpose of this systematic review was to determine the
      characteristics of web-based patient education interventions that are associated
      with producing changes in self-care behaviors. A systematic review involving 19
      studies was conducted to determine the most effective components of a web-based
      intervention. Findings suggest that the most effective form of web-based patient
      education is one that is interactive and allows patients to navigate the online
      system on their own. The findings from this systematic review allow for the
      design of a web-based educational intervention that will promote increased
      performance of self-care behaviors during the home recovery period. 

PMID- 24571964
TI  - Using mixed-method assessment to advance adolescent HIV prevention.
AB  - This two-phase, community-based pilot study examined the impact of an innovative
      calendar-based assessment on HIV risk perception and risk reduction planning with
      racially diverse youth aged 14 to 21 at a public health clinic. Participants (N =
      232) completed a Sexual Health History Calendar (SHHC) assessing behaviors over
      the previous 12 months, risk self-appraisals, and future behavioral intentions.
      Youths' narratives included negative self-appraisals (36%), named a risk-related
      critical incident (13%) or regret (9%), or expressed increased risk awareness
      (9%) and need for behavior change (18%). A minority were positive (28%) or
      reflected improvement (7%). All Phase 2 participants (n = 122) identified at
      least one specific risky behavior they intended to change. These data and the
      SHHC's visual cues facilitated risk-reduction intervention tailored to the unique
      circumstances in which each youth's risk taking occurred. For nurses and other
      providers in clinical settings, the SHHC can offer a critical link between
      assessment and intervention. 

PMID- 24571966
TI  - Pandemic potential of emerging influenza.

PMID- 24571967
TI  - Debt burden of Greece and HIV among injecting drug users.

PMID- 24571968
TI  - Editor's note.

PMID- 24571965
TI  - Improvement of organic solvent tolerance by disruption of the lon gene in
      Escherichia coli.
AB  - The Lon ATP-dependent protease plays an important role in regulating many
      biological processes in bacteria. In this study, we examined the organic solvent
      tolerance of a Deltalon mutant of Escherichia coli K-12 and found that the mutant
      showed remarkably higher organic solvent tolerance than the parent strain.
      Deltalon mutants are known to overproduce capsular polysaccharide, resulting in
      the formation of mucoid colonies. We considered that this increase in capsular
      polysaccharide production might be involved in the organic solvent tolerance in
      E. coli. However, a DeltalonDeltawcaJ double-gene mutant displaying a nonmucoid
      phenotype was as tolerant to organic solvents as the Deltalon mutant, suggesting
      that capsular polysaccharide is not involved in organic solvent tolerance. On the
      other hand, the Lon protease is known to exhibit proteolytic activity against the
      transcriptional activators MarA and SoxS, which can enhance the expression level
      of the AcrAB-TolC efflux pump. We found that the Deltalon mutant showed a higher
      expression level of AcrB than the parent strain. In addition, the
      DeltalonDeltaacrB double-gene mutant showed a significant decrease in organic
      solvent tolerance. Thus, it was shown that organic solvent tolerance in the
      Deltalon mutant depends on the AcrAB-TolC pump but not capsular polysaccharide.
      E. coli strain JA300 acrRIS marR overexpresses the AcrAB-TolC pump and exhibits
      high-level solvent tolerance. In an attempt to further improve the solvent
      tolerance of JA300 acrRIS marR, a lon gene disruptant of this strain was
      constructed. However, the resulting mutant JA300 acrRIS marR Deltalon showed
      lower solvent tolerance than JA300 acrRIS marR.

PMID- 24571969
TI  - Soil-transmitted helminth infections in South America.

PMID- 24571970
TI  - Soil-transmitted helminth infections in South America.

PMID- 24571971
TI  - Decreased susceptibility to cephalosporins among gonococci?

PMID- 24571972
TI  - Decreased susceptibility to cephalosporins among gonococci?

PMID- 24571973
TI  - Decreased susceptibility to cephalosporins among gonococci? Authors' reply.

PMID- 24571974
TI  - Decreased susceptibility to cephalosporins among gonococci?

PMID- 24571976
TI  - Measurement of vaccine confidence using media surveillance system--authors'
      reply.

PMID- 24571975
TI  - Measurement of vaccine confidence using media surveillance system.

PMID- 24571977
TI  - Procalcitonin as a diagnostic marker for sepsis.

PMID- 24571979
TI  - Fever and rash in an immunocompromised child.

PMID- 24571980
TI  - A simple and reliable health monitoring system for shoulder health: proposal.
AB  - BACKGROUND: The current health care system is complex and inefficient. A simple
      and reliable health monitoring system that can help patients perform medical self
      diagnosis is seldom readily available. Because the medical system is vast and
      complex, it has hampered or delayed patients in seeking medical advice or
      treatment in a timely manner, which may potentially affect the patient's chances
      of recovery, especially those with severe sicknesses such as cancer, and heart
      disease. OBJECTIVE: The purpose of this paper is to propose a methodology in
      designing a simple, low cost, Internet-based health-screening platform. METHODS:
      This health-screening platform will enable patients to perform medical self
      diagnosis over the Internet. Historical data has shown the importance of early
      detection to ensure patients receive proper treatment and speedy recovery.
      RESULTS: The platform is designed with special emphasis on the user interface.
      Standard Web-based user-interface design is adopted so the user feels ease to
      operate in a familiar Web environment. In addition, graphics such as charts and
      graphs are used generously to help users visualize and understand the result of
      the diagnostic. The system is developed using hypertext preprocessor (PHP)
      programming language. One important feature of this system platform is that it is
      built to be a stand-alone platform, which tends to have better user privacy
      security. The prototype system platform was developed by the National Cheng Kung
      University Ergonomic and Design Laboratory. CONCLUSIONS: The completed prototype
      of this system platform was submitted to the Taiwan Medical Institute for
      evaluation. The evaluation of 120 participants showed that this platform system
      is a highly effective tool in health-screening applications, and has great
      potential for improving the medical care quality for the general public.

PMID- 24571981
TI  - Proper connectivity of Drosophila motion detector neurons requires Atonal
      function in progenitor cells.
AB  - BACKGROUND: Vertebrates and invertebrates obtain visual motion information by
      channeling moving visual cues perceived by the retina through specific motion
      sensitive synaptic relays in the brain. In Drosophila, the series of synaptic
      relays forming the optic lobe are known as the lamina, medulla, lobula and lobula
      plate neuropiles. The fly's motion detection output neurons, called the T4 and T5
      cells, reside in the lobula plate. Adult optic lobe neurons are derived from
      larval neural progenitors in two proliferating compartments known as the outer
      and inner proliferation centers (OPC and IPC). Important insight has been gained
      into molecular mechanisms involved in the development of the lamina and medulla
      from the OPC, though less is known about the development of the lobula and lobula
      plate. RESULTS: Here we show that the proneural gene Atonal is expressed in a
      subset of IPC progenitors that give rise to the higher order motion detection
      neurons, T4 and T5, of the lobula plate. We also show that Atonal does not act as
      a proneural gene in this context. Rather, it is required specifically in IPC
      neural progenitors to regulate neurite outgrowth in the neuronal progeny.
      CONCLUSIONS: Our findings reveal that a proneural gene is expressed in
      progenitors but is required for neurite development of their progeny neurons.
      This suggests that transcriptional programs initiated specifically in progenitors
      are necessary for subsequent neuronal morphogenesis.

PMID- 24571982
TI  - Effects of four chemotherapeutic agents, bleomycin, etoposide, cisplatin, and
      cyclophosphamide, on DNA damage and telomeres in a mouse spermatogonial cell
      line.
AB  - Treatment with chemotherapeutics agents may induce persistent DNA damage in male
      germ cells with the possibility of long-term consequences on fertility and
      progeny outcome. Telomeres, specialized structures at the physical ends of
      chromosomes, play an important role in the maintenance of genetic stability and
      in the response of somatic cells to anticancer drugs. Our objective was to test
      the hypothesis that exposure to bleomycin, etoposide, or cisplatin (the drugs
      used to treat testicular cancer) or cyclophosphamide (an anticancer agent and
      immunosuppressant) targets telomeres in the male germ line. C18-4 spermatogonial
      cells were exposed to bleomycin, etoposide, cisplatin, or 4
      hydroperoxycyclophosphamide (4OOH-CPA, a preactivated analog of
      cyclophosphamide). All four anticancer drugs induced a significant increase in
      DNA damage in C18-4 cells, as assessed by gamma-H2AX immunofluorescence.
      Interestingly, the gamma-H2AX signal was localized to telomeres after treatment
      with bleomycin, cisplatin, and 4OOH-CPA, but not etoposide. Mean telomere
      lengths, the intensity of the telomere fluorescence in situ hybridization signal,
      telomerase activity, and the expression of the telomerase enzyme mRNA components,
      Tert and Terc, were reduced by exposure to cisplatin and 4OOH-CPA, but not by
      bleomycin or etoposide. Thus, although all four anticancer drugs induced DNA
      damage in this spermatogonial cell line, telomeres were not specifically affected
      by etoposide and only the two alkylating agents, cisplatin and 4OOH-CPA, induced
      telomere dysfunction. This telomere dysfunction may contribute to infertility and
      developmental defects in the offspring. 

PMID- 24571983
TI  - Wt1 is involved in leydig cell steroid hormone biosynthesis by regulating
      paracrine factor expression in mice.
AB  - Wilms tumor gene, Wt1, is abundantly expressed in testis Sertoli cells. Our
      recent study demonstrated that Wt1 is involved in spermatogenesis by regulating
      Sertoli cell polarity. In the present study, we found that Wt1 is also required
      for steroidogenesis in Leydig cells and that deletion of the Wt1 gene resulted in
      defects in testosterone biosynthesis and downregulation of steroidogenic gene
      expression, including cytochrome P450 side-chain cleavage (P450scc),
      steroidogenic acute regulatory protein (StAR), 3beta-hydroxysteroid dehydrogenase
      I (3beta-HSD), and cytochrome P450 17A1 (Cyp17a1). The expression of LHR was
      significantly decreased in Wt1(-/flox); Cre-ER(TM) testes after tamoxifen
      induction, whereas the luteinizing hormone level in serum was unchanged. Further
      studies revealed that desert hedgehog (Dhh) expression was regulated by Wt1 in
      Sertoli cells and that its expression was significantly reduced in Wt1-deficient
      testes. In vitro study demonstrated that the defect in testosterone production
      and decreased expression of several steroidogenic genes in Wt1-deficient testis
      explants was partially rescued by smoothened agonist (SAG), a hedgehog pathway
      agonist. These results indicate that Wt1 is most likely involved in Leydig cell
      steroidogenesis by regulating the expression of paracrine factors in seminiferous
      tubules. Dhh probably had important roles in this process, but we could not
      exclude the possibility that other factors were also required for Leydig cell
      steroidogenesis. Loss of Wt1 leads to downregulation of paracrine factors, which
      in turn causes a decrease in steroidogenic enzyme expression and reduces
      testosterone production in Leydig cells. The results of this study further
      confirm that the cross talk between Sertoli cells and Leydig cells has important
      roles in Leydig cell steroidogenesis. 

PMID- 24571984
TI  - Human amniotic fluid stem cells possess the potential to differentiate into
      primordial follicle oocytes in vitro.
AB  - Previous reports have demonstrated that embryonic stem cells were capable of
      differentiating into primordial germ cells through the formation of embryoid
      bodies that subsequently generated oocyte-like cells (OLCs). Such a process could
      facilitate studies of primordial follicle oocyte development in vitro and
      regenerative medicine. To investigate the pluripotency of human amniotic fluid
      stem cells (hAFSCs) and their ability to differentiate into germ cells, we
      isolated a CD117(+)/CD44(+) hAFSC line that showed fibroblastoid morphology and
      intrinsically expressed both stem cell markers (OCT4, NANOG, SOX2) and germ cell
      markers (DAZL, STELLA). To encourage differentiation into OLCs, the hAFSCs were
      first cultured in a medium supplemented with 5% porcine follicular fluid for 10
      days. During the induction period, cell aggregates formed and syntheses of
      steroid hormones were detected; some OLCs and granulosa cell-like cells could be
      loosened from the surface of the culture dish. Cell aggregates were collected and
      replated in oocyte culture medium for an additional 7-10 days. OLCs ranging from
      50 to 120 MUm presenting zona pellucida were observed in cumulus-oocyte
      complexes; some OLCs developed spontaneously into multicell structures similar to
      preimplantation embryos. Approximately 2% of the hAFSCs differentiated to meiotic
      germ cells that expressed folliculogenesis- and oogenesis-associated markers.
      Although the in vitro maturation and fertilization potentials are as yet
      unproven, short-term (<25 days) and high-efficiency (>2%) derivation of OLCs from
      hAFSCs might provide a new approach to the study of human germ cell development
      in vitro. 

PMID- 24571985
TI  - Glucocorticoids sensitize rat placental inflammatory responses via inhibiting
      lipoxin A4 biosynthesis.
AB  - Inflammation dysregulation in placenta is implicated in the pathogenesis of
      numerous pregnancy complications. Glucocorticoids (GCs), universally considered
      anti-inflammatory, can also exert proinflammatory actions under some conditions,
      whereas whether and how GCs promote placental inflammation have not been
      intensively investigated. In this paper we report the opposing regulation of rat
      placental inflammation by synthetic GC dexamethasone (Dex). When Dex was
      subcutaneously injected 1 h after we administered an intraperitoneal
      lipopolysaccharide (LPS) challenge, neutrophil infiltration and proinflammatory
      Il1b, Il6, and Tnfa expression in rat placenta were significantly reduced. In
      contrast, Dex pretreatment for 24 h potentiated rat placental proinflammatory
      response to LPS and delayed inflammation resolution, which involved MAPKs and NF
      kappaB activation. Mechanically, Dex pretreatment promoted 5-lipoxygenase (ALOX5)
      activation and increased leukotriene B4 production, whereas it inhibited the anti
      inflammatory and proresolving lipid mediator lipoxin A4 (LXA4) biosynthesis in
      rat placenta via downregulating ALOX15 and ALOX15B expression. Moreover, LXA4
      supplementation dampened Dex-potentiated placental inflammation and suppressed
      Dex-mediated ALOX5 activation in vivo and in vitro. Taken together, these
      findings suggest that GCs exposure could promote placental inflammation
      initiation and delay resolution via disrupting LXA4 biosynthesis. 

PMID- 24571986
TI  - Loss of the proapoptotic BH3-only protein BCL-2 modifying factor prolongs the
      fertile life span in female mice.
AB  - The duration of the female fertile life span is influenced by the number of
      oocytes stored in the ovary as primordial follicles. Cell death, both during
      ovarian development in the embryo and in the postnatal ovary, plays a critical
      role in determining how many primordial follicles are established and maintained
      within the ovary. However, the roles of individual apoptotic regulators in
      mediating cell death within the ovary have not yet been characterized. In this
      study, gene targeted mice were used to investigate the role of BCL-2-modifying
      factor (BMF), a proapoptotic protein belonging to the BH3-only subgroup of the
      BCL-2 family, in determining the number of primordial follicles maintained in the
      adult ovary and the length of the fertile life span. Stereological analysis of
      ovaries showed that Bmf(-/-) mice had significantly more primordial follicles
      than wild-type (WT) control animals at Postnatal Days 100, 200, 300, and 400 but
      not at Day 20. No differences were observed between WT and Bmf(-/-) mice in the
      number of ova shed following ovulatory stimulation with exogenous gonadotropins.
      Bmf(-/-) females were fertile and produced the same number pups/litter as WT
      females, but Bmf(-/-) females produced litters more frequently and consequently
      more offspring than WT females over a 6-mo period. Furthermore, the fertile life
      span of Bmf(-/-) females was significantly extended compared to WT females. Our
      findings support an important role for BMF in determining the number of
      primordial follicles maintained in the ovary throughout adult reproductive life
      and thus indicate that the length of female fertility may be extended by
      increasing the number of primordial follicles maintained within the ovary through
      inhibition of BMF. 

PMID- 24571989
TI  - Epigenetics of human myometrium: DNA methylation of genes encoding contraction
      associated proteins in term and preterm labor.
AB  - Preterm birth involves the interaction of societal and environmental factors
      potentially modulating the length of gestation via the epigenome. An established
      form of epigenetic regulation is DNA methylation where promoter hypermethylation
      is associated with gene repression. We hypothesized we would find differences in
      DNA methylation in the myometrium of women with preterm labor of different
      phenotypes versus normal term labor. Myometrial tissue was obtained at cesarean
      section at term with or without labor, preterm without labor, idiopathic preterm
      labor, and twin gestations with labor. Genomic DNA was isolated, and samples in
      each group were combined and analyzed on a NimbleGen 2.1M human DNA methylation
      array. Differences in methylation from -8 to +3 kb of transcription start sites
      of 22 contraction-associated genes were determined. Cytosine methylation was not
      present in CpG islands of any gene but was present outside of CpG islands in
      shores and shelves in 19 genes. No differential methylation was found across the
      tissue groups for six genes (PTGES3L, PTGER2, PTGER4, PTGFRN, ESR2, and GJA1).
      For 13 genes, differential methylation occurred in several patterns between
      tissue groups. We find a correlation between hypomethylation and increased mRNA
      expression of PTGES/mPGES-1, indicating potential functional relevance of
      methylation, but no such correlation for PTGS2/COX-2, suggesting other regulatory
      mechanisms for PTGS2 at labor. The majority of differential DNA methylation of
      myometrial contraction-associated genes with different labor phenotypes occurs
      outside of CpG islands in gene promoters, suggesting that the entirety of DNA
      methylation across the genome should be considered. 

PMID- 24571988
TI  - Leptin-promoted human extravillous trophoblast invasion is MMP14 dependent and
      requires the cross talk between Notch1 and PI3K/Akt signaling.
AB  - The overexpression of leptin is a crucial feature for the maintenance of
      pregnancy. The effects of leptin on trophoblast invasion are important to its
      reproductive function, but the underlying mechanisms remain poorly understood.
      MMP14 is a member of matrix metalloproteinase (MMP) family that is closely
      involved in the invasion process. Here, we characterized the importance of MMP14
      in the proinvasion effect of leptin on EVT cells and elucidated its molecular
      mechanisms. Transwell assay revealed that leptin promoted invasion of the
      immortalized EVT cell line HTR-8/SVneo in a dose- and time-related fashion.
      Further studies suggested that leptin enhanced HTR-8/SVneo cell invasion by up
      regulating MMP14 expression and that knockdown of MMP14 by small interference RNA
      (siRNA) blocked the proinvasion effect of leptin. Notably, leptin promoted the
      expression of Notch1 receptor and activated its signaling in HTR-8/SVneo cells,
      and blocking this pathway by siRNA inhibited both leptin-enhanced MMP14
      expression and invasiveness of HTR-8/SVneo cells. Such effects of Notch1
      signaling were related with the activation of the PI3K/Akt pathway, which was
      significantly activated after leptin stimulation and was interfered by Notch1
      signaling perturbation. Taken together, our observations suggest that leptin is
      an effective regulator of MMP14 expression, which consequently plays critical
      roles in invasion of EVT cells. The promoting effects of leptin on MMP14 require
      the cross talk between Notch1 and PI3K/Akt signaling pathways. 

PMID- 24571991
TI  - Biomechanics of the elbow.
AB  - This article examines the basic structure and function of the elbow from a
      biomechanical perspective. Kinematics, including types and ranges of motion are
      described. Anatomical and functional parameters related to joint stability and
      loading patterns are discussed in relation to joint kinetics. A final section
      summarizes pertinent EMG findings related to elbow function. 

PMID- 24571990
TI  - Surgical treatment of pheochromocytoma in MEN 2.
AB  - Multiple endocrine neoplasia type 2 (MEN 2) is a rare autosomal dominant cancer
      syndrome. Forty to fifty percent of patients with MEN 2A develops
      pheochromocytoma. Surgeons treating these patients with pheochromocytoma have
      always been faced with question of whether to perform mono-or bilateral
      adrenalectomy and the timing of surgical intervention. Over the past 20 years,
      thanks to the development of ever more sophisticated techniques of diagnostic
      imaging (TC, MRI, Scintigraphy, PET), which make it possible to identify small
      lesions, and to ever more rapid laboratory tests, there has been a change in the
      surgical management of this condition. Surgeons moved from bilateral open
      adrenalectomy (6- 9) to laparoscopic partial adrenalectomy and cortical sparing
      (10-13). After partial adrenalectomy one third of the patients require
      replacement therapy because the function of the residual parenchyma was
      compromised by excessive devascularization during surgery. In patients with
      bilateral pheochromocytoma it is advisable to perform only partial adrenalectomy
      of at least one gland, i.e. to completely remove the gland with the larger lesion
      and remove part of the gland with the smaller lesion to reduce the risk of
      recurrence. The authors report 4 cases of MEN 2, including 2 first-degree
      relatives, which illustrate the progress made in surgical treatment for
      pheochromocytoma.

PMID- 24571987
TI  - A murine uterine transcriptome, responsive to steroid receptor coactivator-2,
      reveals transcription factor 23 as essential for decidualization of human
      endometrial stromal cells.
AB  - Recent data from human and mouse studies strongly support an indispensable role
      for steroid receptor coactivator-2 (SRC-2)-a member of the p160/SRC family of
      coregulators-in progesterone-dependent endometrial stromal cell decidualization,
      an essential cellular transformation process that regulates invasion of the
      developing embryo into the maternal compartment. To identify the key progesterone
      induced transcriptional changes that are dependent on SRC-2 and required for
      endometrial decidualization, we performed comparative genome-wide transcriptional
      profiling of endometrial tissue RNA from ovariectomized SRC-2(flox/flox) (SRC
      2(f/f) [control]) and PR(cre/+)/SRC-2(flox/flox) (SRC-2(d/d) [SRC-2-depleted])
      mice, acutely treated with vehicle or progesterone. Although data mining revealed
      that only a small subset of the total progesterone-dependent transcriptional
      changes is dependent on SRC-2 (~13%), key genes previously reported to mediate
      progesterone-driven endometrial stromal cell decidualization are present within
      this subset. Along with providing a more detailed molecular portrait of the
      decidual transcriptional program governed by SRC-2, the degree of functional
      diversity of these progesterone mediators underscores the pleiotropic regulatory
      role of SRC-2 in this tissue. To showcase the utility of this powerful
      informational resource to uncover novel signaling paradigms, we stratified the
      total SRC-2-dependent subset of progesterone-induced transcriptional changes in
      terms of novel gene expression and identified transcription factor 23 (Tcf23), a
      basic-helix-loop-helix transcription factor, as a new progesterone-induced target
      gene that requires SRC-2 for full induction. Importantly, using primary human
      endometrial stromal cells in culture, we demonstrate that TCF23 function is
      essential for progesterone-dependent decidualization, providing crucial
      translational support for this transcription factor as a new decidual mediator of
      progesterone action. 

PMID- 24571992
TI  - Anatomy and examination of the elbow.
AB  - The treatment of elbow injuries necessitates establishment of a proper diagnosis.
      An understanding of anatomic relationships serves as the basis for clinical
      evaluation. The history must ascertain the details of specific injury as well as
      identify intrinsic and extrinsic risk factors. Physical examination includes
      inspection, range of motion testing, palpation, provocative testing, and
      neuromuscular testing. Radiologic and ancillary testing supplement the clinical
      evaluation. 

PMID- 24571993
TI  - Overuse injuries of the elbow.
AB  - Overuse injuries result from repetitive microtrauma that can lead to inflammation
      and local tissue damage in the form of cellular and extracellular degeneration.
      The elbow, secondary to its central positioning, is predisposed to an array of
      injuries that are often companion to associated pathology of the spine, shoulder,
      and hand/wrist complex. An understanding of etiology and rehabilitative
      management will assist the clinician in the diagnosis and treatment of common
      overuse injuries involving the elbow. 

PMID- 24571994
TI  - Entrapment Neuropathies about the Elbow.
AB  - The differential diagnosis of symptoms such as numbness, paresthesias, pain, or
      weakness in the hand must include entrapment neuropathies which can occur about
      the elbow region. Several potential entrapment sites have been described for the
      major peripheral nerves during their course down the upper arm and into the
      proximal forearm. With a well-directed history, physical and electrodiagnostic
      examination the localization of a specific entrapment site is possible. 

PMID- 24571995
TI  - Pediatric elbow injury.
AB  - The increasing involvement of children in sport and fitness related activity has
      been parallel by an increase in the frequency of sports-related childhood injury.
      Immature, open epiphyses, as well as soft articular cartilage predispose children
      to age-specific injury. An understanding of osseous development, normal
      radiologic variants, and the diagnosis and treatment of common elbow injuries in
      the pediatric population will assist the clinician who treats younger patients. 

PMID- 24571996
TI  - Surgical aspects of tennis elbow tendinosis.
AB  - Tennis elbow tendinosis represents a degenerative change in the forearm
      musculature resulting from chronic repetitive activity. Most cases of tennis
      elbow will respond favorably to an aggressive rehabilitation program. A small
      percentage of cases, however, may not respond adequately and may therefore
      benefit from surgical management. In 1979, Nirschl and Pettrone introduced a new
      technique for the surgical treatment of tennis elbow. The key to this technique,
      which has been applied to lateral, medial, and posterior tennis elbow, is
      identification and removal of pathologic angiofibroblastic tendinosis. Surgical
      management is followed by aggressive postoperative rehabilitation. 

PMID- 24571997
TI  - Neurologic pain syndromes in cancer patients.
AB  - Painful neurological syndromes in cancer patients require comprehensive clinical
      assessment for their accurate diagnosis. Early diagnosis of the painful
      neurological syndromes in cancer patients allows the clinician to target his
      therapy toward preventing escalating pain, disability, and further neurological
      morbidity. Active rehabilitation is critically important in the management of
      these patients with neurological pain syndromes. Rehabilitation helps prevent
      further pain due to the development of secondary problems of immobility or
      disuse, helps the individual patient achieve his maximal level of functioning and
      helps each patient adapt to his/her neurological deficits. 

PMID- 24572001
TI  - From the editor.

PMID- 24571998
TI  - Return to work for patients with low back pain: two case studies.
AB  - Dismal return to work rates and mounting disability costs in the chronic low back
      pain (LBP) population imply the need for innovative re-employment strategies. The
      supported employment approach utilizes a vocational specialist under close
      physician supervision. It is more proactive, less biased, and more specialized
      than the more traditional case management approach used by many insurance
      companies. Supported employment has been used extensively at our institution in
      the brain injured population and we have recently begun exploring its use in LBP
      patients. Herein, we describe the successful use of supported employment in two
      individuals with chronic disabling LBP. 

PMID- 24572002
TI  - Introduction.

PMID- 24572003
TI  - Nonsurgical management of tennis elbow.

PMID- 24572004
TI  - Deposition of F-doped ZnO transparent thin films using ZnF2-doped ZnO target
      under different sputtering substrate temperatures.
AB  - Highly transparent and conducting fluorine-doped ZnO (FZO) thin films were
      deposited onto glass substrates by radio-frequency (RF) magnetron sputtering,
      using 1.5 wt% zinc fluoride (ZnF2)-doped ZnO as sputtering target. Structural,
      electrical, and optical properties of the FZO thin films were investigated as a
      function of substrate temperature ranging from room temperature (RT) to 300
      degrees C. The cross-sectional scanning electron microscopy (SEM) observation and
      X-ray diffraction analyses showed that the FZO thin films were of polycrystalline
      nature with a preferential growth along (002) plane perpendicular to the surface
      of the glass substrate. Secondary ion mass spectrometry (SIMS) analyses of the
      FZO thin films showed that there was incorporation of F atoms in the FZO thin
      films, even if the substrate temperature was 300 degrees C. Finally, the effect
      of substrate temperature on the transmittance ratio, optical energy gap, Hall
      mobility, carrier concentration, and resistivity of the FZO thin films was also
      investigated. 

PMID- 24572005
TI  - Trends and changes in prescription opioid analgesic dispensing in Canada 2005
      2012: an update with a focus on recent interventions.
AB  - BACKGROUND: Prescription opioid analgesic (POA) utilization has steeply increased
      globally, yet is far higher in established market economies than elsewhere.
      Canada features the world's second-highest POA consumption rates. Following
      increases in POA-related harm, several POA control interventions have been
      implemented since 2010. METHODS: We examined trends and patterns in POA
      dispensing in Canada by province for 2005-2012, including a focus on the
      potential effects of interventions. Data on annual dispensing of individual POA
      formulations--categorized into 'weak opioids' and 'strong opioids'--from a
      representative sub-sample of 5,700 retail pharmacies across Canada (from IMS
      Brogan's Compuscript) were converted into Defined Daily Doses (DDD), and examined
      intra- and inter-provincially as well as for Canada (total). RESULTS: Total POA
      dispensing--driven by strong opioids--increased across Canada until 2011; four
      provinces indicated decreases in strong opioid dispensing; seven provinces
      indicated decreases specifically in oxycodone dispensing, 2011-2012. The
      dispensing ratio weak/strong opioids decreased substantively. Major inter
      provincial differences in POA dispensing levels and qualitative patterns of POA
      formulations dispensed persisted. Previous increasing trends in POA dispensing
      were reversed in select provinces 2011-2012, coinciding with POA-related
      interventions. CONCLUSIONS: Further examinations regarding the sustained nature,
      drivers and consequences of the recent trend changes in POA dispensing--including
      possible 'substitution effects' for oxycodone reductions--are needed.

PMID- 24572006
TI  - Prehospital stroke diagnostics based on neurological examination and transcranial
      ultrasound.
AB  - BACKGROUND: Transcranial color-coded sonography (TCCS) has proved to be a fast
      and reliable tool for the detection of middle cerebral artery (MCA) occlusions in
      a hospital setting. In this feasibility study on prehospital sonography, our aim
      was to investigate the accuracy of TCCS for neurovascular emergency diagnostics
      when performed in a prehospital setting using mobile ultrasound equipment as part
      of a neurological examination. METHODS: Following a '911 stroke code' call,
      stroke neurologists experienced in TCCS rendezvoused with the paramedic team. In
      patients with suspected stroke, TCCS examination including ultrasound contrast
      agents was performed. Results were compared with neurovascular imaging (CTA, MRA)
      and the final discharge diagnosis from standard patient-centered stroke care.
      RESULTS: We enrolled '232 stroke code' patients with follow-up data available in
      102 patients with complete TCCS examination. A diagnosis of ischemic stroke was
      made in 73 cases; 29 patients were identified as 'stroke mimics'. MCA occlusion
      was diagnosed in ten patients, while internal carotid artery (ICA) occlusion/high
      grade stenosis leading to reversal of anterior cerebral artery flow was diagnosed
      in four patients. The initial working diagnosis 'any stroke' showed a sensitivity
      of 94% and a specificity of 48%. 'Major MCA or ICA stroke' diagnosed by mobile
      ultrasound showed an overall sensitivity of 78% and specificity of 98%.
      CONCLUSIONS: The study demonstrates the feasibility and high diagnostic accuracy
      of emergency transcranial ultrasound assessment combined with neurological
      examinations for major ischemic stroke. Future combination with telemedical
      support, point-of-care analysis of blood serum markers, and probability
      algorithms of prehospital stroke diagnosis including ultrasound may help to speed
      up stroke treatment.

PMID- 24572008
TI  - Electron and force microscopy characterization of particle size effects and
      surface phenomena associated with individual natural organic matter fractions.
AB  - Natural organic matter (NOM) generically refers to organic substances found in
      soils, waters, and sediments. It is the brown-to-black, heterogeneous organic
      material produced through the diagenetic alteration of plant tissue and microbial
      biomass via a myriad of biotic and abiotic reactions. Since NOM is the primary
      source of organic carbon in the earth's surficial environment, understanding the
      processes by which NOM is produced is integral to understanding carbon
      sequestration, contaminant fate and transport, and other earth surface processes.
      NOM samples (HA0) consist of nonamphiphilic (HA1), lipid-like (L0 and L1), and
      strongly amphiphilic (HA2) components. Here we present the structure and
      morphology of self-assembled NOM components based on scanning electron microscopy
      (SEM), atomic force microscopy (AFM), and electrostatic force microscopy (EFM)
      characterizations. Effects of surface charge and hydrophobicity/hydrophilicity of
      the amphiphile on the interaction and resulting structures were investigated
      using SEM, AFM, and EFM. Data shows that the component's amphiphilic nature plays
      a key role in the formation of NOM. SEM data show that aggregates form while
      AFM/EFM analysis verifies the existence of hydrophobic/hydrophilic moieties in
      different fractions of HA0. Subsequently, the amphiphilic nature of HA2 will have
      a substantial effect on interfacial interactions and subsequent self-assembly of
      HA0's components. 

PMID- 24572007
TI  - Factors that influence the willingness of young adults in Dar es Salaam,
      Tanzania, to participate in phase I/II HIV vaccine trials.
AB  - BACKGROUND: HIV/AIDS continues to destroy the lives of young people especially in
      low-income countries. The inclusion of youths in HIV vaccine trials is of utmost
      importance in obtaining an effective vaccine that is acceptable to them.
      OBJECTIVE: To characterize the willingness of young adults in Tanzania to
      participate in an HIV vaccine trial and the factors that influence this
      willingness. DESIGN: Four hundred and fifty young adults who visited a youth
      friendly Infectious Diseases Clinic (IDC) from February 2012 to September 2012
      completed a self-administered questionnaire concerning sociodemographic
      information, their knowledge about and perception of HIV vaccine studies, and the
      availability of social support. RESULT: Of our participants, 50.6% expressed
      willingness to participate in HIV vaccine trials, and this willingness was
      positively correlated with having some knowledge about HIV vaccine studies (AOR,
      2.2; 95% CI: 1.4-3.4), a positive perception toward such studies (AOR, 2.3; 95%
      CI: 1.5-3.6), having a relationship with someone who could help them make a
      decision (AOR, 2.5; 95% CI: 1.3-4.9), and age at the time of sexual debut (AOR,
      2.6; 95% CI 1.0-6.7) for 15- to 19-year-olds and (AOR, 2.7; 95% CI 1.0-7.1) for
      older participants. CONCLUSION: The participants exhibited a moderate willingness
      to participate in HIV vaccine trials, which was associated with a positive
      perception of and some knowledge about such trials, having a relationship with
      someone who might influence their decision as well as age at time of sexual
      debut. More efforts should be made to inform the youths about specific HIV
      vaccine trials and related matters, as well as to engage significant others in
      the decision-making process.

PMID- 24572010
TI  - Comparing face-to-face and online qualitative research with people with multiple
      sclerosis.
AB  - We compared face-to-face focus groups and an online forum in qualitative research
      with people with multiple sclerosis (MS) and family members. Although the merits
      and challenges of online qualitative research have been considered by others,
      there is limited literature directly comparing these two data collection methods
      for people with disability or chronic illness. Twenty-seven people participated
      in one of four focus groups and 33 people took part in an online forum.
      Demographic and MS-related characteristics were similar between the two groups,
      with a slight nonsignificant trend toward nonmetropolitan residence in online
      forum participants. There was a high level of overlap in the themes generated
      between groups. Participant responses in the online forum were more succinct and
      on-topic, yet in the focus groups interaction was greater. Online qualitative
      research methods can facilitate research participation for people with chronic
      illness or disability, yielding generally comparable information to that gathered
      via face-to-face methods. 

PMID- 24572009
TI  - Epidemiology of transthyretin-associated familial amyloid polyneuropathy in the
      Majorcan area: Son Llatzer Hospital descriptive study.
AB  - BACKGROUND: Transthyretin-associated Familial Amyloid Polyneuropathy (TTR-FAP) is
      an autosomal dominant disease caused by the deposition of abnormal transthyretin
      that results from a gene mutation. Although rare worldwide, there are
      descriptions of several endemic foci, such as in Majorca, Balearic Islands,
      Spain. We aimed at describing a contemporary series of TTR-FAP patients in Son
      Llatzer Hospital in Majorca from an epidemiological point of view in order to
      report their main clinical and laboratory characteristics. METHODS: A
      retrospective, observational study was performed. Medical records from adult
      patients diagnosed with TTR-FAP from a single hospital were reviewed. RESULTS:
      Out of a total of 107 cases, 75 subjects were included: asymptomatic carriers
      (52.3%) and symptomatic patients (47.7%). Mean age was 58.3 years at the time of
      the study, and 50.7% were men. Mean age at diagnosis was 49.8 years. In addition,
      42 patients (39.2%) had received a liver transplant, and time to liver
      transplantation was on average 29.56 months from the initial diagnosis. They all
      had the Val30Met mutation. The organs of the nervous system were those most
      frequently impaired (57.3%), and 83.9% of the symptomatic patients were fully
      ambulant (stage 1). Family history was reported in 69.3% of the cases, with the
      patient's father being the most commonly affected relative. Comorbidities were
      frequent, with high blood pressure being the most common. CONCLUSIONS: Our
      findings provide additional information on this condition and are useful for
      describing the demographic features, clinical presentation, diagnosis, and
      natural course of TTR-FAP in Majorca.

PMID- 24572011
TI  - Internalizing motivation to self-care: a multifaceted challenge for young liver
      transplant recipients.
AB  - The transition from parent-controlled care to self-managed care represents an
      important challenge for adolescents with chronic conditions. We sought to gain a
      deeper understanding of the factors influencing the internalization of motivation
      to self-care in adolescent liver transplant recipients. We conducted a
      qualitative study using in-depth interviews with 18 young patients. We
      triangulated the data collected from the patients with data from parents and
      health care providers, and used an inductive approach to analyze the data. Our
      results illustrate three interrelated challenges that impact on young patients'
      motivation to self-care: (a) the cognitive challenge of fully understanding one's
      condition and personal health risks; (b) the behavioral challenge of developing
      independence regarding self-management issues; and (c) the psychological
      challenge of building a sense of self-ownership and purpose. The latter involves
      overcoming the trauma of survival and coming to terms with feelings of
      obligation, two challenges inherent to transplantation that warrant further
      investigation. 

PMID- 24572012
TI  - In their own voices: methodological considerations in narrative disability
      research.
AB  - Individuals with disabilities continue to experience exclusion from mainstream
      contexts amid stereotypical constructions of disability as an inferior status. To
      address these inequities, we contend that the ramifications for both theory and
      praxis in disability research rests heavily on the way in which disability is
      theorized. In this article, we draw on the findings of a narrative inquiry as a
      context to frame an alternative theoretical model for disability research at both
      individual and social levels. We propose the efficacy of an integrated
      theoretical approach using the vehicle of narrative inquiry to present
      alternative stories by individuals with disabilities themselves. In alignment
      with a poststructuralist epistemology, we propose the addition of Lacanian
      psychoanalysis to address the construct of internalized oppression felt at an
      individual psychological level. We conclude that the epistemological and
      ontological lens through which research is conceptualized has the power either to
      subjugate or to emancipate individual experience. 

PMID- 24572013
TI  - An in-depth, exploratory assessment of the implementation of the National Health
      Information System at a district level hospital in Tanzania.
AB  - BACKGROUND: A well functioning Health Information System (HIS) is crucial for
      effective and efficient health service delivery. In Tanzania there is a national
      HIS called Mfumo wa Taarifa za Uendeshaji Huduma za Afya (MTUHA). It comprises a
      guideline/manual, a series of registers for primary data collection and secondary
      data books where information from the registers is totalled or used for
      calculations. METHODS: A mix of qualitative methods were used. These included key
      informant interviews; staff interviews; participant observations; and a
      retrospective analysis of the hospital's 2010 MTUHA reporting documents and the
      hospital's development plan. RESULTS: All staff members acknowledged data
      collection as part of their job responsibilities. However, all had concerns about
      the accuracy of MTUHA data. Access to training was limited, mathematical
      capabilities often low, dissemination of MTUHA knowledge within the hospital
      poor, and a broad understanding of the HIS's full capabilities lacking.Whilst
      data collection for routine services functioned reasonably well, filling of the
      secondary data tools was unsatisfactory. Internal inconsistencies between the
      different types of data tools were found. These included duplications, and the
      collection of data that was not further used. Sixteen of the total 72 forms
      (22.2%) that make up one of the key secondary data books (Hospital data/MTUHA
      book 2) could not be completed with the information collected in the primary data
      books.Moreover, the hospital made no use of any of the secondary data. The
      hospital's main planning document was its development plan. Only 3 of the 22
      indicators in this plan were the same as indicators in MTUHA, the information for
      9 more was collected by the MTUHA system but figures had to be extracted and
      recalculated to fit, while for the remaining 10 indicators no use could be made
      of MTUHA at all. CONCLUSION: The HIS in Tanzania is very extensive and it could
      be advisable to simplify it to the core business of data collection for routine
      services. Alternatively, the more comprehensive, managerial aspects could be
      sharpened for each type of facility, with a focus upon the hospital level. In
      particular, hospital planning documents need to be more closely aligned with
      MTUHA indicators.

PMID- 24572014
TI  - Preparation and antibacterial properties of titanium-doped ZnO from different
      zinc salts.
AB  - To research the relationship of micro-structures and antibacterial properties of
      the titanium-doped ZnO powders and probe their antibacterial mechanism, titanium
      doped ZnO powders with different shapes and sizes were prepared from different
      zinc salts by alcohothermal method. The ZnO powders were characterized by X-ray
      powder diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR),
      ultraviolet-visible spectroscopy (UV-vis), scanning electron microscopy (SEM),
      transmission electron microscopy (TEM), and selected area electron diffraction
      (SAED), and the antibacterial activities of titanium-doped ZnO powders on
      Escherichia coli and Staphylococcus aureus were evaluated. Furthermore, the
      tested strains were characterized by SEM, and the electrical conductance
      variation trend of the bacterial suspension was characterized. The results
      indicate that the morphologies of the powders are different due to preparation
      from different zinc salts. The XRD results manifest that the samples synthesized
      from zinc acetate, zinc nitrate, and zinc chloride are zincite ZnO, and the
      sample synthesized from zinc sulfate is the mixture of ZnO, ZnTiO3, and ZnSO4 .
      3Zn (OH)2 crystal. UV-vis spectra show that the absorption edges of the titanium
      doped ZnO powders are red shifted to more than 400 nm which are prepared from
      zinc acetate, zinc nitrate, and zinc chloride. The antibacterial activity of
      titanium-doped ZnO powders synthesized from zinc chloride is optimal, and its
      minimum inhibitory concentration (MIC) and minimum bactericidal concentration
      (MBC) are lower than 0.25 g L-1. Likewise, when the bacteria are treated by ZnO
      powders synthesized from zinc chloride, the bacterial cells are damaged most
      seriously, and the electrical conductance increment of bacterial suspension is
      slightly high. It can be inferred that the antibacterial properties of the
      titanium-doped ZnO powders are relevant to the microstructure, particle size, and
      the crystal. The powders can damage the cell walls; thus, the electrolyte is
      leaked from cells. 

PMID- 24572015
TI  - Chromera velia, endosymbioses and the rhodoplex hypothesis--plastid evolution in
      cryptophytes, alveolates, stramenopiles, and haptophytes (CASH lineages).
AB  - The discovery of Chromera velia, a free-living photosynthetic relative of
      apicomplexan pathogens, has provided an unexpected opportunity to study the algal
      ancestry of malaria parasites. In this work, we compared the molecular footprints
      of a eukaryote-to-eukaryote endosymbiosis in C. velia to their equivalents in
      peridinin-containing dinoflagellates (PCD) to reevaluate recent claims in favor
      of a common ancestry of their plastids. To this end, we established the draft
      genome and a set of full-length cDNA sequences from C. velia via next-generation
      sequencing. We documented the presence of a single coxI gene in the mitochondrial
      genome, which thus represents the genetically most reduced aerobic organelle
      identified so far, but focused our analyses on five "lucky genes" of the Calvin
      cycle. These were selected because of their known support for a common origin of
      complex plastids from cryptophytes, alveolates (represented by PCDs),
      stramenopiles, and haptophytes (CASH) via a single secondary endosymbiosis with a
      red alga. As expected, our broadly sampled phylogenies of the nuclear-encoded
      Calvin cycle markers support a rhodophycean origin for the complex plastid of
      Chromera. However, they also suggest an independent origin of apicomplexan and
      dinophycean (PCD) plastids via two eukaryote-to-eukaryote endosymbioses. Although
      at odds with the current view of a common photosynthetic ancestry for alveolates,
      this conclusion is nonetheless in line with the deviant plastome architecture in
      dinoflagellates and the morphological paradox of four versus three plastid
      membranes in the respective lineages. Further support for independent
      endosymbioses is provided by analysis of five additional markers, four of them
      involved in the plastid protein import machinery. Finally, we introduce the
      "rhodoplex hypothesis" as a convenient way to designate evolutionary scenarios
      where CASH plastids are ultimately the product of a single secondary
      endosymbiosis with a red alga but were subsequently horizontally spread via
      higher-order eukaryote-to-eukaryote endosymbioses. 

PMID- 24572016
TI  - Increased substitution rates surrounding low-complexity regions within primate
      proteins.
AB  - Previous studies have found that DNA-flanking low-complexity regions (LCRs) have
      an increased substitution rate. Here, the substitution rate was confirmed to
      increase in the vicinity of LCRs in several primate species, including humans.
      This effect was also found among human sequences from the 1000 Genomes Project. A
      strong correlation was found between average substitution rate per site and
      distance from the LCR, as well as the proportion of genes with gaps in the
      alignment at each site and distance from the LCR. Along with substitution rates,
      dN/dS ratios were also determined for each site, and the proportion of sites
      undergoing negative selection was found to have a negative relationship with
      distance from the LCR. 

PMID- 24572019
TI  - Gait disorders in adults: a classification for their differential diagnosis.
AB  - The increasing frequency and prevalence of functionally significant gait
      disorders in adults requires that more physicians become familiar with systematic
      assessment and treatment approaches. The classification system presented can help
      physicians organize their observations and their clinical management of patients
      with gait problems. 

PMID- 24572020
TI  - Mobility disorders in older adults: the role of deconditioning.
AB  - Deconditioning is a prevalent problem in our sedentary society and is
      increasingly contributing to functional mobility problems in older adults.
      Information about exercise and appropriate exercise programs are increasingly
      available. Physicians and other health care professionals should identify when
      deconditioning is contributing to a patient's mobility problem and then assist
      the patient in developing a new exercise habit. 

PMID- 24572017
TI  - Ascidian mitogenomics: comparison of evolutionary rates in closely related taxa
      provides evidence of ongoing speciation events.
AB  - Ascidians are a fascinating group of filter-feeding marine chordates
      characterized by rapid evolution of both sequences and structure of their nuclear
      and mitochondrial genomes. Moreover, they include several model organisms used to
      investigate complex biological processes in chordates. To study the evolutionary
      dynamics of ascidians at short phylogenetic distances, we sequenced 13 new
      mitogenomes and analyzed them, together with 15 other available mitogenomes,
      using a novel approach involving detailed whole-mitogenome comparisons of
      conspecific and congeneric pairs. The evolutionary rate was quite homogeneous at
      both intraspecific and congeneric level, and the lowest congeneric rates were
      found in cryptic (morphologically undistinguishable) and in morphologically very
      similar species pairs. Moreover, congeneric nonsynonymous rates (dN) were up to
      two orders of magnitude higher than in intraspecies pairs. Overall, a clear-cut
      gap sets apart conspecific from congeneric pairs. These evolutionary
      peculiarities allowed easily identifying an extraordinary intraspecific
      variability in the model ascidian Botryllus schlosseri, where most pairs show a
      dN value between that observed at intraspecies and congeneric level, yet
      consistently lower than that of the Ciona intestinalis cryptic species pair.
      These data suggest ongoing speciation events producing genetically distinct B.
      schlosseri entities. Remarkably, these ongoing speciation events were
      undetectable by the cox1 barcode fragment, demonstrating that, at low
      phylogenetic distances, the whole mitogenome has a higher resolving power than
      cox1. Our study shows that whole-mitogenome comparative analyses, performed on a
      suitable sample of congeneric and intraspecies pairs, may allow detecting not
      only cryptic species but also ongoing speciation events. 

PMID- 24572021
TI  - The use of exercise in the elderly to enhance functional mobility and prevent
      falls.
AB  - Many studies have been conducted to document the positive effects of exercise in
      the elderly. Initially, the focus was on the benefits of aerobic training,
      however, more recent studies have shown that the elderly respond to isometric,
      isotonic, and isokinetic programs. Strength and mobility are two of the key
      factors in assessing a person's risk for falling. Studies have shown that people
      who fall frequently have weaker ankle dorsiflexors and knee extensors than
      persons who do not fall. As a result, it has been speculated that exercise
      programs to strengthen these muscle groups will improve functional mobility and
      reduce the risk of falling. At present ongoing trials are trying to provide
      documentation to support this idea. 

PMID- 24572018
TI  - Mutations enabling displacement of tryptophan by 4-fluorotryptophan as a
      canonical amino acid of the genetic code.
AB  - The 20 canonical amino acids of the genetic code have been invariant over 3
      billion years of biological evolution. Although various aminoacyl-tRNA
      synthetases can charge their cognate tRNAs with amino acid analogs, there has
      been no known displacement of any canonical amino acid from the code.
      Experimental departure from this universal protein alphabet comprising the
      canonical amino acids was first achieved in the mutants of the Bacillus subtilis
      QB928 strain, which after serial selection and mutagenesis led to the HR23 strain
      that could use 4-fluorotryptophan (4FTrp) but not canonical tryptophan (Trp) for
      propagation. To gain insight into this displacement of Trp from the genetic code
      by 4FTrp, genome sequencing was performed on LC33 (a precursor strain of HR23),
      HR23, and TR7 (a revertant of HR23 that regained the capacity to propagate on
      Trp). Compared with QB928, the negative regulator mtrB of Trp transport was found
      to be knocked out in LC33, HR23, and TR7, and sigma factor sigB was mutated in
      HR23 and TR7. Moreover, rpoBC encoding RNA polymerase subunits were mutated in
      three independent isolates of TR7 relative to HR23. Increased expression of sigB
      was also observed in HR23 and in TR7 growing under 4FTrp. These findings
      indicated that stabilization of the genetic code can be provided by just a small
      number of analog-sensitive proteins, forming an oligogenic barrier that
      safeguards the canonical amino acids throughout biological evolution. 

PMID- 24572022
TI  - The geriatric athlete.
AB  - More individuals over the age of 55 are becoming involved in athletics and
      physical fitness. These individuals benefit from this increased activity in a
      number of ways: improved cardiovascular function, improved muscle strength and
      functional ability, and less medical care. By following a gradual, low-intensity
      exercise program, an elderly individual can reap all of the benefits of improved
      physical fitness with little chance of injury. As physicians who care for elderly
      individuals, we need to be cognizant of the benefits and risk involved with
      geriatric athletes. 

PMID- 24572023
TI  - Shoulder problems in the elderly.
AB  - Shoulder disorders, typically characterized by pain and diminished range of
      motion, is a common source of musculoskeletal pain in the elderly. Degenerative
      changes predominate in the elderly shoulder. Like younger patients rotator cuff
      and bicipital tendon disorders are common. Unlike younger patients elderly
      patients are more likely to suffer from shoulder pain as a consequence of a
      frozen shoulder, polymyalgia rheumatica, degenerative arthritis, referred pain
      especially from visceral sources, and hemiplegic shoulder pain. The usefulness of
      high technological diagnostic tests such as magnetic resonance imaging (MRI) is
      very questionable in the elderly because it rarely influences management, which
      is invariably conservative in the elderly. 

PMID- 24572024
TI  - A rheumatologic perspective on rehabilitation of shoulder problems in the older
      individual.
AB  - Shoulder dysfunction is a common but complex clinical problem among the aged. The
      shoulder is a diarthrodial joint that is designed to complement the elbow and
      wrist in stabilizing the arm and the hand. This complex joint has the greatest
      range of motion (ROM) of any joint in the human body. Unfortunately, the aging
      process increases the shoulder's vulnerability to many pathological conditions
      that decrease its ROM and interfere with self-care tasks. While initial therapy
      is typically managed by the primary care physician, the complexity of this
      problem often requires consultation across disciplines to assure pertinent
      management. This article provides an overview of rheumatologic considerations
      specific to geriatric persons with shoulder dysfunction. The differential
      diagnosis and issues of treatment and rehabilitation are discussed. 

PMID- 24572025
TI  - Rehabilitation of the old, old stroke patient.
AB  - Geriatric rehabilitation is an ever increasing part of the general physiatrist
      practice. Stroke rehabilitation will continue to make up a large part of that
      practice. Rehabilitation decreases institutionalization thereby decreasing long
      run costs. Stroke rehabilitation also improves quality of life and lengthens
      life. The management of these patients requires expert physiatric care. The most
      effective and least costly treatment option is still to be determined. 

PMID- 24572026
TI  - Public policy issues in geriatric rehabilitation.
AB  - As geriatric rehabilitation confronts major changes in health care funding,
      investigators and practitioners must identify and validate best practices in the
      field. Consistent, convincing outcomes research is lacking in several important
      areas of practice. Lack of scientific support for geriatric rehabilitation
      approaches is a common criticism at present, and may further jeopardize the
      availability of reimbursement in the future. It is, therefore, essential that
      geriatric rehabilitation investigators follow the lead of such influential groups
      as the Institute of Medicine and the Robert Wood Johnson Foundation in developing
      and defining a public policy-oriented research agenda. 

PMID- 24572028
TI  - From the editor.

PMID- 24572029
TI  - Introduction.

PMID- 24572030
TI  - Old age is not a disease.

PMID- 24572031
TI  - Novel approaches and opportunities for cardioprotective signaling through 3',5'
      cyclic guanosine monophosphate manipulation.
AB  - Limiting the injurious effects of myocardial ischemia-reperfusion is a desirable
      therapeutic target, which has been investigated extensively over the last three
      decades. Here we provide an up to date review of the literature documenting the
      experimental and clinical research demonstrating the effects of manipulating cGMP
      for the therapeutic targeting of the injurious effects of ischemic heart disease.
      Augmentation of the cyclic nucleotide cGMP plays a crucial role in many
      cardioprotective signaling pathways. There is an extensive body of literature
      which supports pharmacological targeting of cGMP or upstream activators in models
      of ischemia-reperfusion to limit injury. NO donors have long been utilised to
      manipulate cGMP, and more recently non-NO synthase derived NOx species have been
      investigated, resulting in their evaluation in clinical trials for the treatment
      of ischemic heart disease. Encouraging results demonstrate that natriuretic
      peptides are worthy candidates in manipulating cGMP and its downstream effectors
      to afford cytoprotection. Synthetic ligands have been designed which co-activate
      natriuretic peptide receptors to improve targeting this pathway. Advances have
      been made in targeting the soluble guanylyl cyclase which catalyzes the
      production of cGMP independently of the endogenous ligand NO using NO-independent
      stimulators and activators of sGC. These novel compounds show promise as a new
      class of drugs that target this signaling cascade specifically under pathological
      conditions when endogenous NO production may be compromised. Regulating the
      degradation of cGMP via phosphodiesterase inhibition also shows therapeutic
      potential. It is clear that production and regulation of cGMP is complex, indeed
      its spatial production and cellular distribution are only just emerging. 

PMID- 24572032
TI  - Injectable collagen implant improves survival, cardiac remodeling, and function
      in the early period after myocarditis in rats.
AB  - AIM: Despite clear evidence of immune system involvement in the pathogenesis of
      myocarditis, the treatment of myocarditis remains nonspecific and supportive. We
      sought to test the hypothesis that injection of a collagen-based implant into the
      inflamed myocardium would stabilize the left ventricular (LV) wall and prevent
      adverse remodeling and dysfunction. METHODS AND RESULTS: Autoimmune myocarditis
      was induced in 42 male Lewis rats. Development of myocarditis was evaluated and
      confirmed by serial echocardiography and cardiac magnetic resonance scans, LV
      wall thickening, global and regional LV wall motion abnormalities, and in some
      cases pericardial effusion. Sick animals were randomized to either injectable
      collagen implantation or saline injection into the anterior inflamed myocardium
      14 days after immunization. Significantly, injectable collagen implantation
      improved 31-day survival compared with controls (85.7% vs 50%; P = .03).
      Furthermore, although injectable collagen significantly attenuated LV systolic
      and diastolic dilatation and preserved LV geometry and function, control animals
      developed significant LV dilatation and dysfunction. These favorable effects on
      LV remodeling were confirmed by postmortem morphometry. Significantly, the
      injectable collagen implant attenuated cardiomyocyte hypertrophy and infiltration
      of macrophages and lymphocytes into the myocardium. CONCLUSIONS: The present
      study shows, for the first time, that injectable collagen biomaterial improves
      survival and attenuates cardiac inflammation, cardiomyocyte hypertrophy, LV
      remodeling, and dysfunction in the early period after myocarditis in rats. Our
      findings suggest a new biomaterial-based strategy to ameliorate the devastating
      effects of myocarditis.

PMID- 24572033
TI  - The Listeria monocytogenes LPXTG surface protein Lmo1413 is an invasin with
      capacity to bind mucin.
AB  - Many Gram-positive bacterial pathogens use surface proteins covalently anchored
      to the peptidoglycan to cause disease. Bacteria of the genus Listeria have the
      largest number of surface proteins of this family. Every Listeria genome
      sequenced to date contains more than forty genes encoding surface proteins
      bearing anchoring-domains with an LPXTG motif that is recognized for covalent
      linkage to the peptidoglycan. About one-third of these proteins are present
      exclusively in pathogenic Listeria species, with some of them acting as adhesins
      or invasins that promote bacterial entry into eukaryotic cells. Here, we
      investigated two LPXTG surface proteins of the pathogen L. monocytogenes, Lmo1413
      and Lmo2085, of unknown function and absent in non-pathogenic Listeria species.
      Lack of these two proteins does not affect bacterial adhesion or invasion of host
      cells using in vitro infection models. However, expression of Lmo1413 promotes
      entry of the non-invasive species L. innocua into non-phagocytic host cells, an
      effect not observed with Lmo2085. Moreover, overproduction of Lmo1413, but not
      Lmo2085, increases the invasion rate in non-phagocytic eukaryotic cells of an L.
      monocytogenes mutant deficient in the acting-binding protein ActA. Unexpectedly,
      production of full-length Lmo1413 and InlA exhibited opposite trends in a high
      percentage of L. monocytogenes isolates obtained from different sources. The idea
      of Lmo1413 playing a role as a new auxiliary invasin was also sustained by assays
      revealing that purified Lmo1413 binds to mucin via its MucBP domains. Taken
      together, these data indicate that Lmo1413, which we rename LmiA, for Listeria
      mucin-binding invasin-A, may promote interaction of bacteria with adhesive host
      protective components and, in this manner, facilitate bacterial entry. 

PMID- 24572034
TI  - Enhancement of the effectiveness of graphene as a transparent conductive
      electrode by AgNO3 doping.
AB  - Single-layer graphene sheets have been synthesized by using chemical vapor
      deposition, and subsequently doped with AgNO3 at various doping concentrations
      (n(D)) from 5 to 50 mM. Atomic force microscopy and field emission scanning
      electron microscopy images reveal the formation of ~10-100 nm Ag particles on the
      graphene surface after doping. The type of n doping is confirmed by analyzing the
      n(D)-dependent behaviors of Raman scattering and the work function of the doped
      graphene films. The sheet resistance monotonically decreases to ~173 Omega/sq
      with the increase of n(D) to 50 mM, and the transmittance is reduced by only
      about 3% for the highest n(D). At n(D) = 10 mM optimized doped graphene layers
      with a sheet resistance of 202 Omega/sq and a transmittance of 96% are obtained,
      resulting in a maximum DC conductivity/optical conductivity ratio
      (sigma(DC)/sigma(OP)) of ~45.5, much larger than the minimum industry standard
      (sigma(DC)/sigma(OP) = ~35) for transparent conductive electrodes.

PMID- 24572036
TI  - Human milk oligosaccharides influence maturation of human intestinal Caco-2Bbe
      and HT-29 cell lines.
AB  - Stimulation of gastrointestinal tract maturation is 1 of the many benefits of
      human milk. Human milk oligosaccharides (HMOs) are abundant in human milk and are
      reported to promote enterocyte differentiation in vitro. The objective of this
      study was to assess the impact of 3 predominant HMOs on multiple aspects of
      enterocyte maturation in vitro. Ranging from crypt-like to differentiated
      enterocytes, we used the well-characterized intestinal cell lines HT-29 and Caco
      2Bbe to model early and late stages of differentiation, respectively. With this
      model of the crypt-villus axis made up of preconfluent HT-29, preconfluent Caco
      2Bbe, and postconfluent Caco-2Bbe cultures, we characterized the impact of lacto
      N-neotetraose (LNnT), 2'-fucosyllactose (2'FL), and 6'-sialyllactose on
      epithelial cell kinetics and function. All 3 HMOs dose-dependently inhibited cell
      proliferation in undifferentiated HT-29 and Caco-2Bbe cultures (P < 0.05). In
      contrast to previous reports, only treatment with 2'FL at concentrations similar
      to human milk increased alkaline phosphatase activity by 31% (P = 0.044) in HT-29
      cultures and increased sucrase activity by 54% (P = 0.005) in well-differentiated
      Caco-2Bbe cultures. LNnT at concentrations similar to that reported for human
      milk increased transepithelial resistance by 21% (P = 0.002) in well
      differentiated Caco-2Bbe cells. In summary, all 3 HMOs reduced cell proliferation
      in an epithelial cell model of the crypt-villus axis. However, effects on
      differentiation, digestive function, and epithelial barrier function differed
      between the HMOs tested. These results suggest differential roles for specific
      HMOs in maturation of the gastrointestinal tract. 

PMID- 24572035
TI  - Adherence to a vegetable-fruit-soy dietary pattern or the Alternative Healthy
      Eating Index is associated with lower hip fracture risk among Singapore Chinese.
AB  - Data on overall dietary pattern and osteoporotic fracture risk from population
      based cohorts are limited, especially from Asian populations. This study examined
      the relation between overall diet and hip fracture risk by using principal
      components analysis (PCA) to identify dietary pattern specific to the study
      population and by using the Alternative Healthy Eating Index (AHEI) 2010 to
      assess dietary quality. The Singapore Chinese Health Study is a prospective
      population-based cohort that enrolled 63,257 Chinese men and women (including
      both pre- and postmenopausal women) aged 45-74 y between 1993 and 1998 in
      Singapore. Habitual diet was assessed by using a validated food-frequency
      questionnaire. Two dietary patterns, the vegetable-fruit-soy (VFS) pattern and
      the meat-dim-sum (MDS) pattern, were derived by PCA. Overall dietary quality was
      assessed according to the AHEI 2010, which was defined a priori for chronic
      disease prevention. A Cox regression model was applied with adjustment for
      potential confounders. In both genders, higher scores for the VFS pattern and the
      AHEI 2010 were associated with lower risk of hip fracture in a dose-dependent
      manner (all P-trend <= 0.008). Compared with the lowest quintile, participants in
      the highest quintile had a 34% reduction in risk (HR: 0.66; 95% CI: 0.55, 0.78)
      for the VFS pattern and a 32% reduction in risk (HR: 0.68; 95% CI: 0.58, 0.79)
      for the AHEI 2010. The MDS pattern score was not associated with hip fracture
      risk. An Asian diet rich in plant-based foods, namely vegetables, fruit, and
      legumes such as soy, may reduce the risk of hip fracture. 

PMID- 24572037
TI  - High diet quality is associated with a lower risk of cardiovascular disease and
      all-cause mortality in older men.
AB  - Although diet quality is implicated in cardiovascular disease (CVD) risk, few
      studies have investigated the relation between diet quality and the risks of CVD
      and mortality in older adults. This study examined the prospective associations
      between dietary scores and risk of CVD and all-cause mortality in older British
      men. A total of 3328 men (aged 60-79 y) from the British Regional Heart Study,
      free from CVD at baseline, were followed up for 11.3 y for CVD and mortality.
      Baseline food-frequency questionnaire data were used to generate 2 dietary
      scores: the Healthy Diet Indicator (HDI), based on WHO dietary guidelines, and
      the Elderly Dietary Index (EDI), based on a Mediterranean-style dietary intake,
      with higher scores indicating greater compliance with dietary recommendations.
      Cox proportional hazards regression analyses assessed associations between
      quartiles of HDI and EDI and risk of all-cause mortality, CVD mortality, CVD
      events, and coronary heart disease (CHD) events. During follow-up, 933 deaths,
      327 CVD deaths, 582 CVD events, and 307 CHD events occurred. Men in the highest
      compared with the lowest EDI quartile had significantly lower risks of all-cause
      mortality (HR: 0.75; 95% CI: 0.60, 0.94; P-trend = 0.03), CVD mortality (HR:
      0.63; 95% CI: 0.42, 0.94; P-trend = 0.03), and CHD events (HR: 0.66; 95% CI:
      0.45, 0.97; P-trend = 0.05) but not CVD events (HR: 0.79; 95% CI: 0.60, 1.05; P
      trend = 0.16) after adjustment for sociodemographic, behavioral, and
      cardiovascular risk factors. The HDI was not significantly associated with any of
      the outcomes. The EDI appears to be more useful than the HDI for assessing diet
      quality in relation to CVD and morality risk in older men. Encouraging older
      adults to adhere to the guidelines inherent in the EDI criteria may have public
      health benefits. 

PMID- 24572038
TI  - Associations between dietary fiber and colorectal polyp risk differ by polyp type
      and smoking status.
AB  - The association of dietary fiber intake with colorectal cancer risk is
      established. However, the association may differ between cigarette smokers and
      nonsmokers. We evaluated this hypothesis in a large colonoscopy-based case
      control study. Dietary fiber intakes were estimated by self-administered food
      frequency questionnaire. Unconditional logistic regression analysis was used to
      estimate ORs and 95% CIs with adjustment for potential confounders. Analysis also
      was stratified by cigarette smoking and sex. High dietary fiber intake was
      associated with reduced risk of colorectal polyps (P-trend = 0.003). This
      association was found to be stronger among cigarette smokers (P-trend = 0.006)
      than nonsmokers (P-trend = 0.21), although the test for multiplicative
      interaction was not statistically significant (P = 0.11). This pattern of
      association was more evident for high-risk adenomatous polyps (ADs), defined as
      advanced or multiple ADs (P-interaction smoking and dietary fiber intake = 0.09).
      Among cigarette smokers who smoked >=23 y, a 38% reduced risk of high-risk ADs
      was found to be associated with high intake of dietary fiber compared with those
      in the lowest quartile fiber intake group (P-trend = 0.004). No inverse
      association with dietary fiber intake was observed for low-risk ADs, defined as
      single nonadvanced ADs. Cigarette smoking may modify the association of dietary
      fiber intake with the risk of colorectal polyps, especially high-risk ADs, a well
      established precursor of colorectal cancer. 

PMID- 24572040
TI  - Doubly labeled water is a validated and verified reference standard in nutrition
      research.

PMID- 24572039
TI  - Higher diet quality is associated with decreased risk of all-cause,
      cardiovascular disease, and cancer mortality among older adults.
AB  - Increased attention in dietary research and guidance has been focused on dietary
      patterns, rather than on single nutrients or food groups, because dietary
      components are consumed in combination and correlated with one another. However,
      the collective body of research on the topic has been hampered by the lack of
      consistency in methods used. We examined the relationships between 4 indices--the
      Healthy Eating Index-2010 (HEI-2010), the Alternative Healthy Eating Index-2010
      (AHEI-2010), the alternate Mediterranean Diet (aMED), and Dietary Approaches to
      Stop Hypertension (DASH)--and all-cause, cardiovascular disease (CVD), and cancer
      mortality in the NIH-AARP Diet and Health Study (n = 492,823). Data from a 124
      item food-frequency questionnaire were used to calculate scores; adjusted HRs and
      95% CIs were estimated. We documented 86,419 deaths, including 23,502 CVD- and
      29,415 cancer-specific deaths, during 15 y of follow-up. Higher index scores were
      associated with a 12-28% decreased risk of all-cause, CVD, and cancer mortality.
      Specifically, comparing the highest with the lowest quintile scores, adjusted HRs
      for all-cause mortality for men were as follows: HEI-2010 HR: 0.78 (95% CI: 0.76,
      0.80), AHEI-2010 HR: 0.76 (95% CI: 0.74, 0.78), aMED HR: 0.77 (95% CI: 0.75,
      0.79), and DASH HR: 0.83 (95% CI: 0.80, 0.85); for women, these were HEI-2010 HR:
      0.77 (95% CI: 0.74, 0.80), AHEI-2010 HR: 0.76 (95% CI: 0.74, 0.79), aMED HR: 0.76
      (95% CI: 0.73, 0.79), and DASH HR: 0.78 (95% CI: 0.75, 0.81). Similarly, high
      adherence on each index was protective for CVD and cancer mortality examined
      separately. These findings indicate that multiple scores reflect core tenets of a
      healthy diet that may lower the risk of mortality outcomes, including federal
      guidance as operationalized in the HEI-2010, Harvard's Healthy Eating Plate as
      captured in the AHEI-2010, a Mediterranean diet as adapted in an Americanized
      aMED, and the DASH Eating Plan as included in the DASH score.

PMID- 24572041
TI  - The formation of short-chain fatty acids is positively associated with the blood
      lipid-lowering effect of lupin kernel fiber in moderately hypercholesterolemic
      adults.
AB  - Lupin kernel fiber beneficially modifies blood lipids because of its bile acid
      binding capacity. The aim of this study was to evaluate the preventive effects of
      a lupin kernel fiber preparation on cardiovascular diseases and to clarify
      possible mechanisms. In a randomized, double-blind, controlled crossover trial,
      60 moderately hypercholesterolemic adults (plasma total cholesterol: >5.2 mmol/L)
      passed 3 intervention periods in different orders with a 2-wk washout phase
      between each. Participants consumed either a high-fiber diet containing 25-g/d
      lupin kernel fiber (LF) or citrus fiber (CF), or a low-fiber control diet (CD)
      for 4 wk each. Anthropometric, plasma, and fecal variables were assessed at
      baseline and after the interventions. Contrary to the CF period, total (9%) and
      LDL (12%) cholesterol as well as triacylglycerols (10%) were lower after the LF
      period when compared with the CD period [P <= 0.02, adjusted for baseline, age,
      gender, and body mass index (BMI)]. HDL cholesterol remained unchanged. Moreover,
      the LF period reduced high-sensitivity C-reactive protein (P = 0.02) and systolic
      blood pressure (P = 0.01) when compared with baseline. Bile acid binding could
      not be shown because the excretion of total bile acids remained constant after
      the high-fiber diets. However, the LF period resulted in an enhanced formation of
      the main short-chain fatty acids in comparison with the CD period. During the CF
      period, only acetate increased significantly. Both high-fiber diets led to higher
      satiety and modified nutritional behavior, resulting in significantly lower body
      weight, BMI, and waist circumference compared with the CD period. The blood lipid
      lowering effects of LF are apparently not a result of bile acid binding. Rather,
      we hypothesize for the first time, to our knowledge, that the blood lipid
      lowering effects of LF may be mainly attributed to the formation of short-chain
      fatty acids, specifically propionate and acetate. This trial was registered at
      clinicaltrials.gov as NCT01035086. 

PMID- 24572042
TI  - Social stimulation and corticolimbic reactivity in premenstrual dysphoric
      disorder: a preliminary study.
AB  - BACKGROUND: Premenstrual dysphoric disorder (PMDD), characterized by luteal phase
      induced negative affect and loss of impulse control, often results in compromised
      social interactions. Although amygdala activation is generally linked to negative
      affect, increased amygdala reactivity to aversive stimuli in the luteal phase has
      not been consistently reported in PMDD. We tested the hypothesis that amygdala
      hyper-reactivity in PMDD is symptom specific, rather than generalized, and linked
      to socially relevant stimuli. Blood oxygenation level dependent signal changes
      during exposure to negative images with social and non-social content were
      evaluated in the mid-follicular and late luteal phase of the menstrual cycle.
      Fourteen women with PMDD and 13 healthy controls participated. RESULTS: When
      compared with healthy controls, women with PMDD in the luteal phase had enhanced
      reactivity to social stimuli compared to non-social stimuli in the amygdala and
      insula, but attenuated reactivity in the anterior cingulate cortex. Functional
      couplings between emotion processing and controlling areas were significantly
      different, being positive in women with PMDD and negative in healthy controls.
      Changes in progesterone levels in women with PMDD correlated positively with
      altered amygdala reactivity. CONCLUSIONS: Socially relevant aversive stimulation
      elicited enhanced activity in affective processing brain regions that were
      functionally coupled to compromised activity in cognitive control areas. Because
      increased reactivity correlated positively with alterations in ovarian steroid
      levels, data preliminary support the hypothesis that enhanced progesterone
      sensitivity in PMDD affects corticolimbic processing of social emotions.

PMID- 24572043
TI  - Enhanced chemoprophylactic and clinical efficacy of albendazole formulated as
      solid dispersions in experimental cystic echinococcosis.
AB  - Cystic echinococcosis is a chronic, complex, and still neglected disease.
      Although albendazole has demonstrated efficacy, only about one-third of patients
      experience complete remission or cure and 30-50% of treated patients develop some
      evidence of a therapeutic response. Different strategies have been developed in
      order to improve the albendazole water solubility and dissolution rate. The aim
      of the current work was to investigate the chemoprophylactic and clinical
      efficacy of an albendazole:poloxamer 188 solid dispersion formulation on mice
      infected with Echinococcus granulosus metacestodes. Albendazole formulated as
      solid dispersion had greater chemoprophylactic and clinical efficacy than
      albendazole alone. The improved in therapeutic efficacy could be a consequence of
      the increase in the systemic availability of albendazole sulfoxide. The work
      reported here demonstrates that in vivo treatment with albendazole:poloxamer 188
      impairs the development of the hydatid cysts. This new pharmacotechnically based
      strategy could be a suitable alternative for treating cystic echinococcosis in
      humans. 

PMID- 24572044
TI  - Polymerase chain reaction - restriction fragment length polymorphism analysis for
      the differentiation of Trichinella nativa and Trichinella britovi.
AB  - Recently, Trichinella nativa was identified in foxes in Germany and Poland,
      indicating that the geographical distribution of T. nativa is not restricted to
      areas north of the isotherm -4 degrees C in January. In the European Union,
      legislation requires that a regular monitoring of the occurrence of Trichinella
      spp. in indicator animals such as foxes or raccoon dogs be carried out. The
      Trichinella isolates must also be identified on a species level. The multiplex
      PCR recommended by the Community Reference Laboratory for Trichinella allows
      species identification, yet the differentiation of T. nativa and Trichinella
      britovi, a widespread Trichinella species in the temperate regions of Europe, is
      unstable. We therefore describe an easy and reliable method for the
      differentiation of the two species, which can be utilised to monitor a potential
      spread of T. nativa in Central Europe. 

PMID- 24572045
TI  - Wet-STEM tomography: principles, potentialities and limitations.
AB  - The characterization of biological and inorganic materials by determining their
      three-dimensional structure in conditions closer to their native state is a major
      challenge of technological research. Environmental scanning electron microscopy
      (ESEM) provides access to the observation of hydrated samples in water
      environments. Here, we present a specific device for ESEM in the scanning
      transmission electron microscopy mode, allowing the acquisition of tilt-series
      suitable for tomographic reconstructions. The resolution which can be obtained
      with this device is first determined. Then, we demonstrate the feasibility of
      tomography on wet materials. The example studied here is hydrophilic mesoporous
      silica (MCM-41). Finally, the minimum thickness of water which can be detected is
      calculated from Monte Carlo simulations and compared with the resolution expected
      in the tomograms. 

PMID- 24572046
TI  - Correlation of EGFR, pEGFR and p16INK4 expressions and high risk HPV infection in
      HIV/AIDS-related squamous cell carcinoma of conjunctiva.
AB  - BACKGROUND: Squamous cell carcinoma of conjunctiva has increased tenfold in the
      era of HIV/AIDS. The disease pattern has also changed in Africa, affecting young
      persons, with peak age-specific incidence of 30-39 years, similar to that of
      Kaposi sarcoma, a well known HIV/AIDS defining neoplasm. In addition, the disease
      has assumed more aggressive clinical course. The contributing role of exposure to
      high risk HPV in the development of SCCC is still emerging. OBJECTIVE: The
      present study aimed to investigate if immunohistochemical expressions of EGFR,
      pEGFR and p16, could predict infection with high risk HPV in HIV-related SCCC.
      METHODS: FFPE tissue blocks of fifty-eight cases diagnosed on hematoxylin and
      eosin with SCCC between 2005-2011, and subsequently confirmed from medical
      records to be HIV positive at the department of human pathology, UoN/KNH, were
      used for the study. Immunohistochemistry was performed to assess the expressions
      of p16INK4A, EGFR and pEGFR. This was followed with semi-nested PCR based
      detection and sequencing of HPV genotypes. The sequences were compared with the
      GenBank database, and data analyzed for significant statistical correlations
      using SPSS 16.0. Ethical approval to conduct the study was obtained from KNH-ERC.
      RESULTS: Out of the fifty-eight cases of SCCC analyzed, twenty-nine (50%) had
      well differentiated (grade 1), twenty one (36.2%) moderately differentiated
      (grade 2) while eight (13.8%) had poorly differentiated (grade 3) tumours.
      Immunohistochemistry assay was done in all the fifty eight studied cases, of
      which thirty nine cases (67.2%) were positive for p16INK4A staining, forty eight
      cases (82.8%) for EGFR and fifty one cases (87.9%) showed positivity for p-EGFR.
      HPV DNA was detected in 4 out of 40 SCCC cases (10%) in which PCR was performed,
      with HPV16 being the only HPV sub-type detected. Significant statistical
      association was found between HPV detection and p16INK4 (p=0.000, at 99% C.I) and
      EGFR (p=0.028, at 95% C.I) expressions, but not pEGFR. In addition, the
      expressions of these biomarkers did not show any significant association with
      tumor grades. CONCLUSION: This study points to an association of high risk HPV
      with over expressions of p16INK4A and EGFR proteins in AIDS-associated SCCC.

PMID- 24572048
TI  - [Mothers' difficulty in childrearing classified in terms of their children's
      behavioral characteristics].
AB  - OBJECTIVES: Mothers who experience difficulty in childrearing are becoming
      increasingly more prevalent in Japan. This study described and classified
      mothers' childrearing difficulty in terms of their children's behavioral
      characteristics and related factors. METHODS: Self-administered questionnaires
      were distributed to 818 mothers at their children's 3-year-old health checkup in
      eight suburban cities in Japan. The questionnaire consisted of items assessing
      the mother's experience of difficulty in childrearing for the child undergoing
      the checkup. The subjects were classified into four groups according to their
      children's behavioral characteristics: "low needs," "internalizing behavior,"
      "externalizing behavior," and "comorbid internalizing-externalizing behavior."
      Multiple regression analysis was performed to examine the relationships between
      mothers' difficulty in childrearing and related factors. RESULTS: A total of 775
      respondents were divided as follows: 332 mothers had children with low needs, 104
      had those with internalizing behavior, 230 had those with externalizing behavior,
      and 109 had those with comorbid internalizing-externalizing behavior. Mothers in
      the low needs group showed less childrearing difficulty than did mothers in the
      other groups. Childrearing difficulty increased by group in the following order:
      internalizing, externalizing, and comorbid internalizing-externalizing. In all
      four groups, mothers with low self-efficacy and less appraisal support from their
      family encountered greater childrearing difficulty. In the low needs group,
      experiencing childrearing difficulty with another child was related experiencing
      childrearing difficulty with the child undergoing the checkup. In the
      internalizing behavior group, mothers who had experienced greater difficulty in
      childrearing were more likely to be housewives and of younger age, and were more
      likely to have had boys as the child undergoing the checkup. In the externalizing
      behavior group, mothers with more difficulty in childrearing were more likely to
      be younger and less healthy, have less appraisal support from their friends, and
      live in apartments. In the comorbid internalizing-externalizing group, if the
      mothers were housewives, they were more likely to have difficulty in caring for
      their other children, receive less appraisal support from their friends, and
      experience more difficulty in childrearing. CONCLUSION: The results showed that
      mothers' difficulty in childrearing and the factors related to this difficulty
      differed according to their children's behavioral characteristics. Public health
      nurses could provide more effective care and support to mothers by considering
      children's behavioral characteristics.

PMID- 24572047
TI  - Costs and repeat rates associated with colonoscopy observed in medical claims for
      commercial and Medicare populations.
AB  - BACKGROUND: Colorectal cancer is among the leading causes of cancer and cancer
      related mortality in the United States. The incidence and mortality associated
      with CRC can be reduced with preventive screening. Inadequate bowel preparation
      has been associated with missed adenomas and the need for repeat colonoscopies.
      METHODS: Separate claims source databases were analyzed to determine the costs
      associated with colonoscopy in the commercial and Medicare populations. Observed
      repeat rates for colonoscopy within 4 years of initial screening were also
      examined. RESULTS: Among the 6 most commonly used billing codes, the average
      allowed cost for an episode of colonoscopy in 2010 was $2,146 in the commercial
      population and $1,071 in the Medicare population, with average cost sharing of
      $334 and $275, respectively. The portion of colonoscopies associated with a
      biopsy or polyp removal exceeded 50% in the commercial and Medicare populations.
      Approximately 57% of colonoscopies in the commercial population were associated
      with claims for a prescription bowel preparation product within 30 days prior to
      the procedure. Three branded and three generic bowel cleansing products accounted
      for approximately 75% of the total number of prescription claims for colonoscopy.
      Given literature reports that up to 25% of patients receive inadequate bowel
      preparation, the rate of repeat colonoscopy within 4 years of initial screening
      was lower than expected among patients who were not coded with common clinical
      reasons for early repeat: benign neoplasm, lesion, or polyp removed at initial
      screening colonoscopy. CONCLUSIONS: The reported rates of inadequate bowel
      preparation are 15% to 25%, but the rates of repeat colonoscopy found in our
      analysis are much lower; this is a risk concern considering the reported,
      significant miss rate of adenomas secondary to inadequate bowel preparation.

PMID- 24572049
TI  - [The effect of determining birthdays by social factors such as maternal
      preference on the distribution in the number of daily live births].
AB  - OBJECTIVES: To investigate the effect of determining birthdays by social factors
      on the distribution of daily live births. METHODS: We obtained data on live
      births tabulated by date and birthplace (hospitals, clinics, and maternity homes)
      between 1981 and 2010 in Japan from the National Vital Statistics System. This
      study analyzed the variations in live births for each day of the week, as well as
      for several specific days observed to have a systematic variation in the number
      of live births. We determined the ratio of the mean daily live births on those
      specific days to the overall daily average each month (the birth number ratio).
      The standardized deviation (the ratio of the deviation to the standard deviation
      for the day of week) regarding the birth number ratio of each specific day was
      also determined. RESULTS: The birth number ratio in hospitals and clinics was
      highest on Tuesdays and lowest on Sundays. Hospitals showed a large difference in
      the birth number ratio between weekdays and weekends, although the difference in
      the birth number ratio between weekdays and Saturdays was smaller in clinics than
      in hospitals. The birth number ratio during the first three days of the New Year
      was lower than that on Sundays. Until approximately 1995, the standardized
      deviation on February 29th and April 1st (the end of the Japanese school year)
      showed abnormally low values, while those on March 1st and April 2nd showed
      significantly high values. Following that time period, the significant variations
      on February 29th (only on Sundays), April 1st (only on Sundays), March 1st, and
      April 2nd almost completely disappeared. Maternity homes showed equivalent
      results until the 1980s or the middle of the 1990s. CONCLUSION: The variations in
      the days of the week were inconsistent with nationwide policies for consultation
      in each setting. These results indicate that some birth dates were set for
      institutional reasons or maternal preferences (i.e., the day after the leap day
      or the next school year) by using or avoiding obstetric intervention. The
      abnormal variation on leap days and on April 1st might be related to fictitious
      reporting. More recent variations in the birth number ratio on specific days
      suggest that some individuals may avoid obstetric intervention. The results of
      this study indicate that determining birthdays by social factors may have been
      practiced in maternity homes until approximately 1990.

PMID- 24572050
TI  - [The process and factors associated with the establishment of voluntary groups
      among community-dwelling elderly].
AB  - OBJECTIVES: Interviews were conducted with elderly people who had participated in
      the Care-Prevention Leadership Training Course (CPLTC), and had then established
      voluntary groups that practice care-prevention activities. This study examined
      the process and factors associated with the establishment of voluntary groups
      among subjects. METHODS: The subjects were ten 62- to 76-year-old community
      dwelling elderly in Tokyo who had taken the CPLTC. Data were obtained from 40- to
      90-minute semi-structured interviews concerning the process of voluntary-group
      establishment. The data were then qualitatively analyzed using a modified
      grounded theory approach. Some of the concepts associated with the voluntary
      group establishment were extracted, and organized into categories. These
      relationships were comparatively reviewed, and a figure for the results was
      constructed. RESULTS: Subjects went through the following processes and feelings
      while establishing voluntary groups: "feelings that encourage participation in
      the local community," "opportunity for participation in the local community,"
      "recognition of issues in the local community," "recognition of the importance of
      care prevention," "enhanced motivation for voluntary-group activities," and
      "recognition of requirements to establish a voluntary-group through its
      preparation." In addition, related factors were as follows; "past experience,"
      "experience in the local community," "experience in CPLTC," "support in the local
      community," "support in CPLTC," "support in establishment of voluntary groups,"
      and "feelings that promote or inhibit activities for the voluntary-group
      establishment." These processes were considered to be core concepts: "feelings
      and experiences that lead to participation in the local community," "deep
      understanding through experiences in the community and CPLTC," and "enhancement
      of motivation and skills for the activities through voluntary-group preparation."
      CONCLUSION: The results showed that the community-dwelling elderly experienced
      gradual changes in their feelings, awareness, and related factors concerning
      their establishment of voluntary groups. The data showed that three points of
      view were important in those changes: "participation in the local community,"
      "recognition of issues in the local community," and "enhanced motivation and
      skills for community activities." With transition-related factors taken into
      account, it is possible to effectively support elderly who are establishing
      voluntary groups by promoting involvement in the local community, holding
      courses, and providing preparatory support for group establishment.

PMID- 24572051
TI  - [Research on mental health and welfare activities in public health centers].

PMID- 24572054
TI  - The anatomy and biomechanics of the hip joint.
AB  - The human hip is the largest ball and socket joint in the body. It differs in
      design from the more common hinge joint in order to meet the requirements of
      ambulation. The hip is an inherently stable joint because of its bony structure
      and its extensive ligamentous and muscular support. Regardless of this stability,
      the hip joint maintains a wide functional range of movement. This dichotomy of
      function has resulted in a complex organization of joint structure. A thorough
      understanding of the biomechanic forces exerted across the joint surfaces is
      essential to the understanding of both normal and pathologic function.The authors
      of this article will explore the complex structural anatomy of this joint system
      in light of the biomechanic principles that effect movement and weight bearing
      through the joint. 

PMID- 24572052
TI  - Antitumor effects of flavopiridol on human uterine leiomyoma in vitro and in a
      xenograft model.
AB  - Dysregulated cyclin-dependent kinases (CDKs) are considered a potential target
      for cancer therapy. Flavopiridol is a potent CDK inhibitor. In this study, the
      antiproliferative effect of the flavonoid compound flavopiridol and its mechanism
      in human uterine leiomyoma cells were investigated. The present study focused on
      the effect of flavopiridol in cell proliferation and cell cycle progression in
      primary cultured human uterine leiomyoma cells. Cell viability and cell
      proliferation assays were conducted. Flow cytometry was performed to determine
      the effect of flavopiridol on cell cycle. The expression of cell cycle regulatory
      related proteins was evaluated by Western blotting. Cell viability and
      proliferation of uterine leiomyoma cells were significantly reduced by
      flavopiridol treatment in a dose-dependent manner. Flow cytometry results showed
      that flavopiridol induced G1 phase arrest. Flavopiridol-induced growth inhibition
      in uterine leiomyoma cells was associated with increased expression of
      p21(cip/wafl) and p27(kip1) in a dose-dependent manner. Downregulation of CDK2/4
      and Cyclin A with a concomitant increase in dephosphorylation of retinoblastoma
      was observed. This study demonstrates that flavopiridol inhibits cell
      proliferation by initiating G1 cell cycle arrest in human uterine leiomyoma. We
      also found that flavopiridol is effective in inhibiting xenografted human uterine
      leiomyoma growth. These results indicate that flavopiridol could prove to be a
      promising chemopreventive and therapeutic agent for human uterine leiomyoma. 

PMID- 24572055
TI  - Hip pain: differential diagnosis.
AB  - This review discusses the many etiologies of hip pain and how to clinically
      evaluate. Both primary hip disorders and conditions that refer pain to the hip
      are included in the differential diagnosis. The key components to a history are
      reviewed with clinically relevant examples. A comprehensive physical exam is
      described that includes disease and injury-specific tests. Imaging studies and
      diagnostic tests available are outlined. Conditions of bursitis, snapping hip
      syndromes, myofascial pain, fibromyalgia, arthropathies, fractures, neurogenic
      pain, metabolic diseases, and neoplastic disorders will be discussed. 

PMID- 24572056
TI  - Twenty-five Years Before the Fall: Preventing Osteoporotic Hip Fracture.
AB  - Osteoporosis is a common entity, especially among elderly Caucasian women.
      Osteoporosis leads to hip fracture in many persons, putting them at risk for
      death and marked handicap. Hip fracture shows a steady increase in incidence
      after age 60 years, and most of the victims are over age 75 years. Screening
      studies predict hip fracture up to 8 years before fracture. Estrogen therapy, to
      be effective, should be initiated between the ages of 50 and 60 years, 25 to 15
      years before the most likely age of fracture. Guidelines describing for whom the
      physician targets estrogen therapy, which is not without risks, are sketchy or
      nonexistent. The patient should also be educated as a young adult about risk
      factor modification for osteoporosis, including increasing exercise, ceasing
      smoking, and minimizing coffee and alcohol use. 

PMID- 24572057
TI  - Rehabilitation following total hip arthroplasty.
AB  - Rehabilitation professionals play an important role in the comprehensive
      postoperative management of the patient who has undergone a total hip
      replacement. Understanding the general surgical considerations that eventually
      impact the rehabilitation process is essential. Coordination of physicians,
      physical and occupational therapists, social services, and family members results
      in better quality of care. The technology and design of hip prostheses and
      fixation methods impact the functional outcome of total hip arthroplasty.
      Professionals involved in total hip arthroplasty rehabilitation should also
      understand the potential complications following total hip arthroplasty that
      oftentimes cause delays or revisions in the rehabilitation program. When these
      are combined with appropriate preoperative patient selection and education, as
      well as postoperative physical and occupational therapy programs, most patients
      are able to achieve a satisfactory functional outcome, including independence in
      basic activities of daily living and independent ambulation with an assistive
      device. 

PMID- 24572053
TI  - Spending of HIV resources in Asia and Eastern Europe: systematic review reveals
      the need to shift funding allocations towards priority populations.
AB  - INTRODUCTION: It is increasingly important to prioritize the most cost-effective
      HIV interventions. We sought to summarize the evidence on which types of
      interventions provide the best value for money in regions with concentrated HIV
      epidemics. METHODS: We conducted a systematic review of peer-reviewed and grey
      literature reporting measurements of cost-effectiveness or cost-benefit for
      HIV/AIDS interventions in Asia and Eastern Europe. We also collated HIV/AIDS
      spending assessment data from case-study countries in the region. RESULTS: We
      identified 91 studies for inclusion, 47 of which were from peer-reviewed
      journals. Generally, in concentrated settings, prevention of mother-to-child
      transmission programmes and prevention programmes targeting people who inject
      drugs and sex workers had lower incremental cost-effectiveness ratios than
      programmes aimed at the general population. The few studies evaluating programmes
      targeting men who have sex with men indicate moderate cost-effectiveness.
      Collation of prevention programme spending data from 12 countries in the region
      (none of which had generalized epidemics) indicated that resources for the
      general population/non-targeted was greater than 30% for eight countries and
      greater than 50% for five countries. CONCLUSIONS: There is a misalignment between
      national spending on HIV/AIDS responses and the most affected populations across
      the region. In concentrated epidemics, scarce funding should be directed more
      towards most-at-risk populations. Reaching consensus on general principles of
      cost-effectiveness of programmes by epidemic settings is difficult due to
      inconsistent evaluation approaches. Adopting a standard costing, impact
      evaluation, benefits calculation, analysis and reporting framework would enable
      cross comparisons and improve HIV resource prioritization and allocation.

PMID- 24572058
TI  - Venous thromboembolism in the hip surgery patient.
AB  - Venous thromboembolism is the most common and potentially lethal problem
      following elective or emergency hip surgery. Appropriate DVT prophylaxis is
      absolutely essential, as the incidence of both calf and proximal vein thrombosis
      is significant. Two to three percent of postoperative hip patients die secondary
      to pulmonary embolism.Prophylactic measures include a variety of pharmacological
      and non pharmacological tools. Early mobilization, leg exercises, and gradient
      compression stockings constitute a minimum protocol. Low-dose Coumadin or low
      molecular weight heparin should be employed as a pharmacological prophylaxis.If
      deep venous thrombosis is suspected, clinical judgment alone should not be a
      basis for treatment decisions. Venography or, if necessary, other modem
      diagnostic agents must be employed. If appropriate studies are positive,
      aggressive treatment with heparin followed by Coumadin is suggested. 

PMID- 24572059
TI  - Heterotopic ossification after total hip replacement.
AB  - Heterotopic ossification (HO) is a common finding after total hip arthroplasty
      (THA), and may cause diminished hip range of motion and an antalgic gait.
      Although the etiology remains unclear, two theories currently prevail. In this
      article, the incidence, etiology, risk factors, and classifications of HO are
      discussed. Effective prophylactic treatments including radiation and anti
      inflammatory medications are detailed. Once HO is present, the value of these
      treatments are doubtful and surgical excision may be required after bony
      maturity. With increasing THA projected as the population ages, the need for
      safe, effective, and inexpensive prophylaxis may be required. 

PMID- 24572060
TI  - Congenital hip dislocation and pediatric hip disorders.
AB  - The pediatric hip changes through development, leading to a challenging
      evaluation of pain. Common problems noted in children include congenital
      dislocation of the hip, Legg-Calve-Perthes disease, slipped capital femoral
      epiphysis, and transient synovitis. Hip disorders are also seen secondary to
      other childhood diseases, such as spina bifida. Long-term complications of all of
      these hip disorders can lead to joint deformity and osteoarthritis in adulthood. 

PMID- 24572061
TI  - The hip in cerebral palsy.
AB  - The care of the hip in children with cerebral palsy is an ongoing challenge.
      Interventions need to be physiologically based and well timed. Early management
      will prevent future complications in both the ambulatory and nonambulatory child
      with cerebral palsy. Evaluation management and treatment of the hips in cerebral
      palsy will be discussed in this article. 

PMID- 24572062
TI  - Overuse injuries of the hip and pelvis in sport.
AB  - The majority of athletic injuries of the hip and pelvis are caused by overuse.
      Most of these injuries will respond to adequate rehabilitative management,
      including the correction of intrinsic and extrinsic risk factors and controlling
      abusive force loads that may have contributed to injury. In addition to injury
      specific rehabilitation, imbalances and abnormalities at each level of the
      kinetic chain also must be corrected to ensure optimal healing. 

PMID- 24572065
TI  - From the editor.

PMID- 24572063
TI  - The piriformis syndrome: a review.
AB  - Piriformis syndrome is a controversial cause of hip and low back pain whose
      etiology stems from anatomic irregularities of the piriformis muscle and
      surrounding structures of the posterior hip region. Although this syndrome has
      been described by many clinicians, the association of piriformis muscle
      dysfunction and pain in the hip region remains conjectural. The diagnosis is one
      of exclusion of other more common pain generators in the hip, pelvis, or low
      back.The authors of this article will review the anatomy of the region as it
      relates to piriformis muscle dysfunction and delineate the various clinical,
      radiological, and interventional procedures described in the literature to
      diagnose and treat this elusive syndrome. 

PMID- 24572066
TI  - Introduction.

PMID- 24572067
TI  - The confusion of hip pain.

PMID- 24572068
TI  - DNA-templated synthesis of PtAu bimetallic nanoparticle/graphene nanocomposites
      and their application in glucose biosensor.
AB  - In this paper, single-stranded DNA (ss-DNA) is demonstrated to functionalize
      graphene (GR) and to further guide the growth of PtAu bimetallic nanoparticles
      (PtAuNPs) on GR with high densities and dispersion. The obtained nanocomposites
      (PtAuNPs/ss-DNA/GR) were characterized by transmission electron microscopy (TEM),
      energy-dispersive X-ray spectrometer (EDS), and electrochemical techniques. Then,
      an enzyme nanoassembly was prepared by self-assembling glucose oxidase (GOD) on
      PtAuNP/ss-DNA/GR nanocomposites (GOD/PtAuNPs/ss-DNA/GR). The nanocomposites
      provided a suitable microenvironment for GOD to retain its biological activity.
      The direct and reversible electron transfer process between the active site of
      GOD and the modified electrode was realized without any extra electron mediator.
      Thus, the prepared GOD/PtAuNP/ss-DNA/GR electrode was proposed as a biosensor for
      the quantification of glucose. The effects of pH, applied potential, and
      temperature on the performance of the biosensor were discussed in detail and were
      optimized. Under optimal conditions, the biosensor showed a linearity with
      glucose concentration in the range of 1.0 to 1,800 MUM with a detection limit of
      0.3 MUM (S/N = 3). The results demonstrate that the developed approach provides a
      promising strategy to improve the sensitivity and enzyme activity of
      electrochemical biosensors. 

PMID- 24572071
TI  - Laser-induced disaggregation of TiO2 nanofillers for uniform nanocomposites.
AB  - Exploiting the intrinsic photosensitivity of TiO2 nanoparticles, we demonstrated
      how ultraviolet (UV) pulsed laser irradiation of acrylate polymer nanocomposite
      solutions can separate the initial clusters of these colloidal semiconductor
      nanorods into clearly distinct units. From the irradiated solutions, optically
      clear nanocomposite films are obtained which exhibit enhanced optical properties
      with respect to the nanocomposites obtained without previous UV treatment.

PMID- 24572069
TI  - Modeling of chemical inhibition from amyloid protein aggregation kinetics.
AB  - BACKGROUNDS: The process of amyloid proteins aggregation causes several human
      neuropathologies. In some cases, e.g. fibrillar deposits of insulin, the problems
      are generated in the processes of production and purification of protein and in
      the pump devices or injectable preparations for diabetics. Experimental kinetics
      and adequate modelling of chemical inhibition from amyloid aggregation are of
      practical importance in order to study the viable processing, formulation and
      storage as well as to predict and optimize the best conditions to reduce the
      effect of protein nucleation. RESULTS: In this manuscript, experimental data of
      insulin, Abeta42 amyloid protein and apomyoglobin fibrillation from recent
      bibliography were selected to evaluate the capability of a bivariate sigmoid
      equation to model them. The mathematical functions (logistic combined with
      Weibull equation) were used in reparameterized form and the effect of inhibitor
      concentrations on kinetic parameters from logistic equation were perfectly
      defined and explained. The surfaces of data were accurately described by proposed
      model and the presented analysis characterized the inhibitory influence on the
      protein aggregation by several chemicals. Discrimination between true and
      apparent inhibitors was also confirmed by the bivariate equation. EGCG for
      insulin (working at pH = 7.4/T = 37 degrees C) and taiwaniaflavone for Abeta42
      were the compounds studied that shown the greatest inhibition capacity.
      CONCLUSIONS: An accurate, simple and effective model to investigate the
      inhibition of chemicals on amyloid protein aggregation has been developed. The
      equation could be useful for the clear quantification of inhibitor potential of
      chemicals and rigorous comparison among them.

PMID- 24572070
TI  - Comparison of the neuropoietic activity of gene-modified versus parental
      mesenchymal stromal cells and the identification of soluble and extracellular
      matrix-related neuropoietic mediators.
AB  - INTRODUCTION: Transplanting mesenchymal stromal cells (MSCs) or their derivatives
      into a neurodegenerative environment is believed to be beneficial because of the
      trophic support, migratory guidance, immunosuppression, and neurogenic stimuli
      they provide. SB623, a cell therapy for the treatment of chronic stroke,
      currently in a clinical trial, is derived from bone marrow MSCs by using
      transient transfection with a vector encoding the human Notch1 intracellular
      domain. This creates a new phenotype, which is effective in experimental stroke,
      exhibits immunosuppressive and angiogenic activity equal or superior to parental
      MSCs in vitro, and produces extracellular matrix (ECM) that is exceptionally
      supportive for neural cell growth. The neuropoietic activity of SB623 and
      parental MSCs has not been compared, and the SB623-derived neuropoietic mediators
      have not been identified. METHODS: SB623 or parental MSCs were cocultured with
      rat embryonic brain cortex cells on cell-derived ECM in a previously
      characterized quantitative neuropoiesis assay. Changes in expression of rat
      neural differentiation markers were quantified by using rat-specific qRT-PCR.
      Human mediators were identified by using expression profiling, an enzymatic
      crosslinking activity, and functional interference studies by means of blocking
      antibodies, biologic inhibitors, and siRNA. Cocultures were immunolabeled for
      presynaptic vesicular transporters to assess neuronal specialization. RESULTS:
      Among six MSC/SB623 pairs, SB623 induced expression of rat neural precursor,
      oligodendrocyte, and astrocyte markers on average 2.6 to 3 times stronger than
      did their parental MSCs. SB623 expressed significantly higher FGF2, FGF1, and
      BMP4, and lower FGFR1 and FGFR2 levels; and human FGF1, FGF2, BMPs, and HGF were
      implicated as neuropoietic mediators. Neural precursors grew faster on SB623-
      than on MSC-derived ECM. SB623 exhibited higher expression levels and
      crosslinking activity of tissue transglutaminase (TGM2). TGM2 silencing reduced
      neural precursor growth on SB623-ECM. SB623 also promoted the induction of GABA
      ergic, but not glutamatergic, neurons more effectively than did MSCs.
      CONCLUSIONS: These data demonstrate that SB623 cells tend to support neural cell
      growth more effectively than their parental MSCs and identify both soluble and
      insoluble mediators responsible, at least in part, for enhanced neuropoietic
      potency of SB623. The neuropoiesis assay is a useful tool for identifying
      beneficial factors produced by MSCs and their derivatives.

PMID- 24572072
TI  - Interactive effects of CO2 and trace metals on the proteasome activity and
      cellular stress response of marine bivalves Crassostrea virginica and Mercenaria
      mercenaria.
AB  - Increased anthropogenic emission of CO2 changes the carbonate chemistry and
      decreases the pH of the ocean. This can affect the speciation and the
      bioavailability of metals in polluted habitats such as estuaries. However, the
      effects of acidification on metal accumulation and stress response in estuarine
      organisms including bivalves are poorly understood. We studied the interactive
      effects of CO2 and two common metal pollutants, copper (Cu) and cadmium (Cd), on
      metal accumulation, intracellular ATP/ubiquitin-dependent protein degradation,
      stress response and energy metabolism in two common estuarine bivalves
      Crassostrea virginica (eastern oyster) and Mercenaria mercenaria (hard shell
      clam). Bivalves were exposed for 4-5 weeks to clean seawater (control) and to
      either 50 MUg L(-1) Cu or 50 MUg L(-1) Cd at one of three partial pressures of
      CO2 ( [Formula: see text] ~ 395, ~ 800 and ~ 1500 MUatm) representative of the
      present-day conditions and projections of the Intergovernmental Panel for Climate
      Change (IPCC) for the years 2100 and 2250, respectively. Clams accumulated lower
      metal burdens than oysters, and elevated [Formula: see text] enhanced the Cd and
      Cu accumulation in mantle tissues in both species. Higher Cd and Cu burdens were
      associated with elevated mRNA expression of metal binding proteins
      metallothionein and ferritin. In the absence of added metals, proteasome
      activities of clams and oysters were robust to elevated [Formula: see text] , but
      [Formula: see text] modulated the proteasome response to metals. Cd exposure
      stimulated the chymotrypsin-like activity of the oyster proteasome at all CO2
      levels. In contrast, trypsin- and caspase-like activities of the oyster
      proteasome were slightly inhibited by Cd exposure in normocapnia but this
      inhibition was reversed at elevated [Formula: see text] . Cu exposure inhibited
      the chymotrypsin-like activity of the oyster proteasome regardless of the
      exposure [Formula: see text] . The effects of metal exposure on the proteasome
      activity were less pronounced in clams, likely due to the lower metal
      accumulation. However, the general trends (i.e. an increase during Cd exposure,
      inhibition during exposure to Cu, and overall stimulatory effects of elevated
      [Formula: see text] ) were similar to those found in oysters. Levels of mRNA for
      ubiquitin and tumor suppressor p53 were suppressed by metal exposures in
      normocapnia in both species but this effect was alleviated or reversed at
      elevated [Formula: see text] . Cellular energy status of oysters was maintained
      at all metal and CO2 exposures, while in clams the simultaneous exposure to Cu
      and moderate hypercapnia (~ 800 MUatm [Formula: see text] ) led to a decline in
      glycogen, ATP and ADP levels and an increase in AMP indicating energy deficiency.
      These data suggest that environmental CO2 levels can modulate accumulation and
      physiological effects of metals in bivalves in a species-specific manner which
      can affect their fitness and survival during the global change in estuaries.

PMID- 24572073
TI  - Using a multibiomarker approach and behavioural responses to assess the effects
      of anthracene in Palaemon serratus.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are recognised as one of the main groups
      of contaminants that assume more importance in the marine environment, enhancing
      the need of studies concerning their adverse effects and more efficient and
      ecologically relevant tools for environmental monitoring purposes. This study
      aims to apply an integrated approach including several multi-level biological
      responses (accumulation levels, biochemical responses important for different
      physiological functions and behavioural alterations) to assess the ecological
      relevance of the effects induced by sub-lethal concentrations of anthracene (ANT)
      in Palaemon serratus (common prawn). ANT accumulation was assessed by measuring
      the levels of ANT-type compounds in prawn digestive gland, muscle and eye;
      biochemical responses were determined using biomarkers involved in
      biotransformation, oxidative damage, energy production and neurotransmission
      processes; and behavioural alterations through swimming performance after 96 h
      exposure bioassay (ANT:16-1,024 MUg/L). The rationale behind this approach is to
      assess the ecologically relevant effects induced by ANT in prawn, given by the
      association between behavioural alterations with biochemical responses, in search
      for more efficient tools for environmental risk assessment. Results show a
      significant decrease of swimming velocity (LOEC=128 MUg/L) along with increased
      levels of ANT-type compounds in digestive gland (LOEC=128 MUg/L), muscle
      (LOEC=256 MUg/L) and eye (LOEC=32 MUg/L) in prawn exposed to ANT. Increased
      activities of glutathione peroxidase (GPx) and catalase (CAT), involved in anti
      oxidant defence system, were also observed (LOEC=256 MUg/L; 1024MUg/L,
      respectively) in the digestive gland of prawn, induction of oxidative damage in
      lipids (LPO) also occurred (LOEC=32 MUg/L). The inhibition of swimming velocity
      showed a correlation with some biochemical parameters measured, including the
      levels of ANT-type compounds in tissues and LPO, and thus these may be considered
      sensitive and ecologically relevant criteria as well as early warning endpoints
      for assessing polycyclic aromatic compounds exposure effects on marine organisms.

PMID- 24572074
TI  - Stromal vascular fraction improves deep partial thickness burn wound healing.
AB  - OBJECTIVE: The practice of early burn wound excision and wound closure by
      immediate autologous skin or skin substitutes is the preferred treatment in
      extensive deep partial and full-thickness burns. To date there is no proven
      definite medical treatment to decrease burn wound size and accelerate burn wound
      healing in modern clinical practice. Stromal vascular fraction is an autologous
      mixture that has multiple proven beneficial effects on different kinds of wounds.
      In our study, we investigated the effects of stromal vascular fraction on deep
      partial-thickness burn wound healing. METHODS: In this study, 20 Wistar albino
      rats were used. Inguinal adipose tissue of the rats was surgically removed and
      stromal vascular fraction was isolated. Thereafter, deep second-degree burns were
      performed on the back of the rats by hot water. The rats were divided into two
      groups in a randomized fashion. The therapy group received stromal vascular
      fraction, whereas the control group received only physiologic serum by
      intradermal injection. Assessment of the burn wound healing between the groups
      was carried out by histopathologic and immuno-histochemical data. RESULTS:
      Stromal vascular fraction increased vascular endothelial growth factor,
      proliferating cell nuclear antigen index, and reduced inflammation of the burn
      wound. Furthermore, vascularization and fibroblastic activity were achieved
      earlier and observed to be at higher levels in the stromal vascular fraction
      group. CONCLUSIONS: Stromal vascular fraction improves burn wound healing by
      increasing cell proliferation and vascularization, reducing inflammation, and
      increasing fibroblastic activity.

PMID- 24572075
TI  - A national survey of inpatient medication systems in English NHS hospitals.
AB  - BACKGROUND: Systems and processes for prescribing, supplying and administering
      inpatient medications can have substantial impact on medication administration
      errors (MAEs). However, little is known about the medication systems and
      processes currently used within the English National Health Service (NHS). This
      presents a challenge for developing NHS-wide interventions to increase medication
      safety. We therefore conducted a cross-sectional postal census of medication
      systems and processes in English NHS hospitals to address this knowledge gap.
      METHODS: The chief pharmacist at each of all 165 acute NHS trusts was invited to
      complete a questionnaire for medical and surgical wards in their main hospital
      (July 2011). We report here the findings relating to medication systems and
      processes, based on 18 closed questions plus one open question about local
      medication safety initiatives. Non-respondents were posted another questionnaire
      (August 2011), and then emailed (October 2011). RESULTS: One hundred (61% of NHS
      trusts) questionnaires were returned. Most hospitals used paper-based prescribing
      on the majority of medical and surgical inpatient wards (87% of hospitals),
      patient bedside medication lockers (92%), patients' own drugs (89%) and 'one-stop
      dispensing' medication labelled with administration instructions for use at
      discharge as well as during the inpatient stay (85%). Less prevalent were the use
      of ward pharmacy technicians (62% of hospitals) or pharmacists (58%) to order
      medications on the majority of wards. Only 65% of hospitals used drug trolleys;
      50% used patient-specific inpatient supplies on the majority of wards. Only one
      hospital had a pharmacy open 24 hours, but all had access to an on-call
      pharmacist. None reported use of unit-dose dispensing; 7% used an electronic drug
      cabinet in some ward areas. Overall, 85% of hospitals had a double-checking
      policy for intravenous medication and 58% for other specified drugs. "Do not
      disturb" tabards/overalls were routinely used during nurses' drug rounds on at
      least one ward in 59% of hospitals. CONCLUSIONS: Inter- and intra-hospital
      variations in medication systems and processes exist, even within the English
      NHS; future research should focus on investigating their potential effects on
      nurses' workflow and MAEs, and developing NHS-wide interventions to reduce MAEs.

PMID- 24572076
TI  - Radiotherapy for indolent lymphomas: how much is enough?

PMID- 24572078
TI  - HIV prevention research ethics: an introduction to the special issue.
AB  - This special issue of the Journal of Empirical Research on Human Research Ethics
      represents a sampling of projects fostered through the NIDA-funded Fordham
      University HIV Prevention Research Ethics Institute. The first three articles
      employ processes of co-learning to give voice to the experiences of individuals
      recovering from substance abuse and engaged in sex work who have participated in
      HIV prevention studies in the United States, India, and the Philippines. The
      fourth article describes a unique community-based approach to the development of
      research ethics training modules designed to increase participation of American
      Indian and Alaskan Native (AI/AN) tribal members as partners in research on
      health disparities. The last two articles focus a critical scholarly lens on two
      underexamined areas confronting IRB review of HIV research: The emerging and
      continuously changing ethical challenges of using social media sites for
      recruitment into HIV prevention research, and the handling of research-related
      complaints from participants involving perceived research harms or research
      experiences that do not accord with their initial expectations. Together, the
      articles in this special issue identify key ethical crossroads and provide
      suggestions for best practices that respect the values and merit the trust of
      research participants. 

PMID- 24572077
TI  - 4 Gy versus 24 Gy radiotherapy for patients with indolent lymphoma (FORT): a
      randomised phase 3 non-inferiority trial.
AB  - BACKGROUND: Follicular lymphoma has been shown to be highly radiosensitive with
      responses to doses as low as 4 Gy in two fractions. This trial was designed to
      explore the dose response for follicular lymphoma comparing 4 Gy in two fractions
      with 24 Gy in 12 fractions METHODS: FORT is a prospective randomised, unblinded,
      phase 3 non-inferiority study comparing radiotherapy given as 4 Gy in two
      fractions with a standard dose of 24 Gy in 12 fractions. Entry criteria included
      all patients aged over 18 years, having local radiotherapy for radical or
      palliative local control, with follicular lymphoma or marginal zone lymphoma, who
      had received no previous treatment for at least 1 month before. The primary
      outcome was time to local progression analysed on an intention-to-treat basis.
      Randomisation was centralised through the Cancer Research UK and University
      College London Cancer Trials Centre. Radiotherapy target sites were randomised
      (1:1) with minimisation stratified by histology (follicular lymphoma vs marginal
      zone lymphoma), treatment intent (palliative or curative) and centre. This trial
      is registered with ClinicalTrials.gov number, NCT00310167. FINDINGS: 299 sites
      were randomly assigned to 24 Gy and 315 sites to 4 Gy between April 7, 2006, and
      June 8, 2011, at 43 centres in the UK. After a median follow-up of 26 months
      (range 0.39-75.4), 91 local progressions had been recorded (21 in the 24 Gy group
      and 70 in the 4 Gy group). Time to local progression with 4 Gy was not non
      inferior to 24 Gy (hazard ratio 3.42, 95% CI 2.09-5.55, p<0.0001). Eight (3%) of
      282 patients in the 24 Gy group and four (1%) of 300 in the 4 Gy group had acute
      grade 3-4 toxic effects. Four (1%) patients in the 24 Gy group and four (1%)
      patients in the 4 Gy group had late toxic effects. Mucositis was the most common
      event in the 24 Gy group (two patients with acute mucositis and two with late
      mucositis; all grade 3) and was not reported in the 4 Gy group. The most common
      acute effect was pain at the site of irradiation (two patients in the 4 Gy group,
      one patient in the 24 Gy group; all grade 3), and the most common late effect was
      fatigue (two patients in the 4 Gy group, one patient in the 24 Gy group; all
      grade 3). INTERPRETATION: 24 Gy in 12 fractions is the more effective radiation
      schedule for indolent lymphoma and should be regarded as the standard of care.
      However, 4 Gy remains a useful alternative for palliative treatment. FUNDING:
      Cancer Research UK.

PMID- 24572079
TI  - Participant and staff experiences in a peer-delivered HIV intervention with
      injection drug users.
AB  - We explore ethical issues faced by investigators as they conduct research as part
      of a peer-delivered HIV/AIDS risk reduction program for injection drug users
      (IDUs). Staff and participant experiences in peer-delivered interventions among
      IDUs have come under scrutiny by ethics researchers because of their potential to
      inadvertently and negatively impact participant rehabilitation due to continued
      engagement with drug-using networks during the course of outreach. This study
      explores whether enhanced communication of participant concerns and experiences
      with clinic and research staff helps to reduce inadvertent malfeasance in peer
      delivered drug treatment interventions. Results contribute to the development of
      patient support infrastructure in peer-delivered risk reduction programs
      involving IDUs. 

PMID- 24572080
TI  - Confidentiality, privacy, and respect: experiences of female sex workers
      participating in HIV research in Andhra Pradesh, India.
AB  - Female sex workers (FSWs) from Andhra Pradesh, India, who had participated in HIV
      research were interviewed to examine participant perspectives on research ethics.
      Content analysis indicated that aspects of the consent process, staff gender and
      demeanor, study environment, survey content, time requirements for study
      participation, and perceived FSW community support for research were key factors
      influencing whether FSWs perceived their confidentiality and privacy had been
      maintained, and whether they felt the study was conducted respectfully. Findings
      suggest that partnership with community-based organizations and investigation of
      participant's experiences in HIV prevention research can provide critical
      information to best inform research ethics protocols, a particular priority among
      research studies with highly stigmatized populations, such as FSWs. 

PMID- 24572081
TI  - Social and structural constraints on disclosure and informed consent for HIV
      survey research involving female sex workers and their bar managers in the
      Philippines.
AB  - This qualitative study explored the ethical issues of female sex workers' (FSWs)
      participation in HIV prevention research. Twenty female bar/spa workers and 10
      venue managers in the Philippines underwent individual semi-structured
      interviews; three community advisory board meetings informed the study design and
      interpretation of findings. RESULTS: Informed consent was constrained by
      perceived government coercion and skepticism that research results would
      translate into community benefits. Disclosure was constrained by distrust in
      confidentiality and perceived intrusiveness of survey questions. FSWs and
      managers were frustrated by the government's inability to stop police from using
      condoms as evidence of prostitution. Findings suggest HIV interventions move
      beyond didactic prevention workshops to include FSWs in intervention design and
      implementation, and to reduce social and structural constraints on participation.

PMID- 24572082
TI  - A collaborative methodology for investigating the ethical conduct of research on
      female sex workers in the Philippines.

PMID- 24572083
TI  - Capacity building from the inside out: development and evaluation of a CITI
      ethics certification training module for American Indian and Alaska Native
      community researchers.
AB  - Current human subject research training modules fail to capture ethically
      relevant cultural aspects of research involving American Indian and Alaska Native
      (AI/AN) community members. Applying a Community Engaged Research (CEnR) approach,
      we adapted the Collaborative IRB Training Initiative training module "assessing
      risk and benefits." In a two-arm randomized controlled trial, followed by
      debriefing interviews, we evaluated module acceptability and understandability
      (test scores) among 40 reservation-based community members. Participants who took
      the adapted module, compared to those who took the standard module, reported
      higher scores on relevance of the material overall satisfaction, module quiz
      scores, and a trend toward higher self-efficacy. Implications of the efficacy of
      this approach for enhancing ethics training and community participation in
      research within AI/AN and other cultural populations within and outside the
      United States are discussed. 

PMID- 24572084
TI  - Social networking and online recruiting for HIV research: ethical challenges.
AB  - Social networking sites and online advertising organizations provide HIV/AIDS
      researchers access to target populations, often reaching difficult-to-reach
      populations. However, this benefit to researchers raises many issues for the
      protections of prospective research participants. Traditional recruitment
      procedures have involved straightforward transactions between the researchers and
      prospective participants; online recruitment is a more complex and indirect form
      of communication involving many parties engaged in the collecting, aggregating,
      and storing of research participant data. Thus, increased access to online data
      has challenged the adequacy of current and established procedures for
      participants' protections, such as informed consent and privacy/confidentiality.
      Internet-based HIV/AIDS research recruitment and its ethical challenges are
      described, and research participant safeguards and best practices are outlined. 

PMID- 24572085
TI  - Legal and ethical values in the resolution of research-related disputes: how can
      IRBS respond to participant complaints?
AB  - Under US federal regulations, participants providing informed consent must
      receive information regarding whom to contact in case of a research-related
      injury or complaint. Although informed consent processes routinely direct
      participants to contact institutional review boards (IRBs) with questions or
      concerns, there has been little empirical study of the ways in which IRBs act to
      resolve participants' research-related complaints. This article explores
      available literature on participant complaints, considers the responsibilities of
      IRBs in dispute resolution, and outlines a research agenda. As a case study, this
      review considers disputes arising from HIV/AIDS research, focusing on novel
      issues arising from biomedical HIV prevention trials. 

PMID- 24572086
TI  - Ancillary care in South African HIV vaccine trials: addressing needs, drafting
      protocols, and engaging community.
AB  - There has been debate about sponsor-investigator ethical responsibilities to
      address participants' medical needs in trials in resource-constrained contexts.
      Certain ethical guidelines make detailed recommendations. This study explored
      whether ethical guideline recommendations for care in HIV vaccine trials were
      being met, and whether stakeholders were facing difficulties addressed by
      guidelines. It sampled key stakeholders involved in two trials across five sites
      in South Africa, and reviewed relevant documentation. It concluded that sites
      were largely meeting guideline recommendations for addressing needs, with some
      exceeding these. Recommendations for writing protocols were only partially
      achieved. Recommendations for engaging participating community were mostly met,
      except for "moral negotiation" recommendations. Suggestions are made to
      strengthen practices, and to improve guidelines so they address empirical
      concerns.

PMID- 24572088
TI  - Epstein-Barr virus and telomerase: from cell immortalization to therapy.
AB  - Overcoming cellular senescence is strictly required for virus-driven tumors,
      including those associated with Epstein-Barr virus (EBV). This critical step is
      successfully accomplished by EBV through TERT expression and telomerase
      activation in infected cells. We herein review the complex interplay between EBV
      and TERT/telomerase in EBV-driven tumorigenesis. Evidence accumulated so far
      clearly indicates that elucidation of this issue may offer promising
      opportunities for the design of innovative treatment modalities for EBV
      associated malignancies. Indeed, several therapeutic strategies for telomerase
      inhibition have been developed and are being investigated in clinical trials. In
      this respect, our recent finding that TERT inhibition sensitizes EBV+ lymphoma
      cells to antivirals through activation of EBV lytic replication is particularly
      promising and provides a rationale for the activation of clinical studies aimed
      at assessing the effects of combination therapies with TERT inhibitors and
      antivirals for the treatment of EBV-associated malignancies. 

PMID- 24572090
TI  - Equalization and decorrelation in primary visual cortex.
AB  - There are many theories on the purpose of neural adaptation, but evidence remains
      elusive. Here, we discuss the recent work by Benucci et al. (Nat Neurosci 16: 724
      729, 2013), who measured for the first time the immediate effects of adaptation
      on the overall activity of a neuronal population. These measurements confirm two
      long-standing hypotheses about the purpose of adaptation, namely that adaptation
      counteracts biases in the statistics of the environment, and that it maintains
      decorrelation in neuronal stimulus selectivity. 

PMID- 24572089
TI  - Effects of ethanol on glycinergic synaptic currents in mouse spinal cord neurons.
AB  - Ethanol increased the frequency of miniature glycinergic currents [miniature
      inhibitory postsynaptic currents (mIPSCs)] in cultured spinal neurons. This
      effect was dependent on intracellular calcium augmentation, since preincubation
      with BAPTA (an intracellular calcium chelator) or thapsigargin [a
      sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA) pump inhibitor] significantly
      attenuated this effect. Similarly, U73122 (a phospholipase C inhibitor) or 2
      aminoethoxydiphenyl borate [2-APB, an inositol 1,4,5-trisphosphate (IP3) receptor
      (IP3R) inhibitor] reduced this effect. Block of ethanol action was also achieved
      after preincubation with Rp-cAMPS, inhibitor of the adenylate cyclase (AC)/PKA
      signaling pathway. These data suggest that there is a convergence at the level of
      IP3R that accounts for presynaptic ethanol effects. At the postsynaptic level,
      ethanol increased the decay time constant of mIPSCs in a group of neurons (30 +/-
      10% above control, n = 13/26 cells). On the other hand, the currents activated by
      exogenously applied glycine were consistently potentiated (55 +/- 10% above
      control, n = 11/12 cells), which suggests that ethanol modulates synaptic and
      nonsynaptic glycine receptors (GlyRs) in a different fashion. Supporting the role
      of G protein modulation on ethanol responses, we found that a nonhydrolyzable GTP
      analog [guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS)] increased the decay time
      constant in ~50% of the neurons (28 +/- 12%, n = 11/19 cells) but potentiated the
      glycine-activated Cl(-) current in most of the neurons examined (83 +/- 29%, n =
      7/9 cells). In addition, confocal microscopy showed that alpha1-containing GlyRs
      colocalized with Gbeta and Piccolo (a presynaptic cytomatrix protein) in ~40% of
      synaptic receptor clusters, suggesting that colocalization of Gbetagamma and
      GlyRs might account for the difference in ethanol sensitivity at the postsynaptic
      level.

PMID- 24572091
TI  - Organization and trade-off of spectro-temporal tuning properties of duration
      tuned neurons in the mammalian inferior colliculus.
AB  - Neurons throughout the mammalian central auditory pathway respond selectively to
      stimulus frequency and amplitude, and some are also selective for stimulus
      duration. First found in the auditory midbrain or inferior colliculus (IC), these
      duration-tuned neurons (DTNs) provide a potential neural mechanism for encoding
      temporal features of sound. In this study, we investigated how having an
      additional neural response filter, one selective to the duration of an auditory
      stimulus, influences frequency tuning and neural organization by recording single
      unit responses and measuring the dorsal-ventral position and spectral-temporal
      tuning properties of auditory DTNs from the IC of the awake big brown bat
      (Eptesicus fuscus). Like other IC neurons, DTNs were tonotopically organized and
      had either V-shaped, U-shaped, or O-shaped frequency tuning curves (excitatory
      frequency response areas). We hypothesized there would be an interaction between
      frequency and duration tuning in DTNs, as electrical engineering theory for
      resonant filters dictates a trade-off in spectral-temporal resolution: sharp
      tuning in the frequency domain results in poorer resolution in the time domain
      and vice versa. While the IC is a more complex signal analyzer than an electrical
      filter, a similar operational trade-off could exist in the responses of DTNs. Our
      data revealed two patterns of spectro-temporal sensitivity and spatial
      organization within the IC: DTNs with sharp frequency tuning and broad duration
      tuning were located in the dorsal IC, whereas cells with wide spectral tuning and
      narrow temporal tuning were found in the ventral IC. 

PMID- 24572092
TI  - Disturbances of motor unit rate modulation are prevalent in muscles of spastic
      paretic stroke survivors.
AB  - Stroke survivors often exhibit abnormally low motor unit firing rates during
      voluntary muscle activation. Our purpose was to assess the prevalence of
      saturation in motor unit firing rates in the spastic-paretic biceps brachii
      muscle of stroke survivors. To achieve this objective, we recorded the incidence
      and duration of impaired lower- and higher-threshold motor unit firing rate
      modulation in spastic-paretic, contralateral, and healthy control muscle during
      increases in isometric force generated by the elbow flexor muscles. Impaired
      firing was considered to have occurred when firing rate became constant (i.e.,
      saturated), despite increasing force. The duration of impaired firing rate
      modulation in the lower-threshold unit was longer for spastic-paretic (3.9 +/-
      2.2 s) than for contralateral (1.4 +/- 0.9 s; P < 0.001) and control (1.1 +/- 1.0
      s; P = 0.005) muscles. The duration of impaired firing rate modulation in the
      higher-threshold unit was also longer for the spastic-paretic (1.7 +/- 1.6 s)
      than contralateral (0.3 +/- 0.3 s; P = 0.007) and control (0.1 +/- 0.2 s; P =
      0.009) muscles. This impaired firing rate of the lower-threshold unit arose,
      despite an increase in the overall descending command, as shown by the
      recruitment of the higher-threshold unit during the time that the lower-threshold
      unit was saturating, and by the continuous increase in averages of the rectified
      EMG of the biceps brachii muscle throughout the rising phase of the contraction.
      These results suggest that impairments in firing rate modulation are prevalent in
      motor units of spastic-paretic muscle, even when the overall descending command
      to the muscle is increasing. 

PMID- 24572095
TI  - Responses of intact and injured sural nerve fibers to cooling and menthol.
AB  - Intact and injured cutaneous C-fibers in the rat sural nerve are cold sensitive,
      heat sensitive, and/or mechanosensitive. Cold-sensitive fibers are either low
      threshold type 1 cold sensitive or high-threshold type 2 cold sensitive. The
      hypothesis was tested, in intact and injured afferent nerve fibers, that low
      threshold cold-sensitive afferent nerve fibers are activated by the transient
      receptor potential melastatin 8 (TRPM8) agonist menthol, whereas high-threshold
      cold-sensitive C-fibers and cold-insensitive afferent nerve fibers are menthol
      insensitive. In anesthetized rats, activity was recorded from afferent nerve
      fibers in strands isolated from the sural nerve, which was either intact or
      crushed 6-12 days before the experiment distal to the recording site. In all, 77
      functionally identified afferent C-fibers (30 intact fibers, 47 injured fibers)
      and 34 functionally characterized A-fibers (11 intact fibers, 23 injured fibers)
      were tested for their responses to menthol applied to their receptive fields
      either in the skin (10 or 20%) or in the nerve (4 or 8 mM). Menthol activated all
      intact (n = 12) and 90% of injured (n = 20/22) type 1 cold-sensitive C-fibers; it
      activated no intact type 2 cold-sensitive C-fibers (n = 7) and 1/11 injured type
      2 cold-sensitive C-fibers. Neither intact nor injured heat- and/or
      mechanosensitive cold-insensitive C-fibers (n = 25) and almost no A-fibers (n =
      2/34) were activated by menthol. These results strongly argue that cutaneous type
      1 cold-sensitive afferent fibers are nonnociceptive cold fibers that use the
      TRPM8 transduction channel. 

PMID- 24572096
TI  - Dopamine neurons coding prediction errors in reward space, but not in aversive
      space: a matter of location?
AB  - Dopamine midbrain neurons are well known for prediction error coding in a reward
      context. A recent report by Christopher Fiorillo (Science 341: 546-549, 2013),
      however, suggests that these neurons behave markedly different when subjects get
      confronted with aversive, rather than appetitive, stimuli. Despite his findings
      being in line with indications of appetitive and aversive stimuli being processed
      by distinct neurotransmitter systems, they should still be interpreted with some
      caution due to a potential issue of recording location. 

PMID- 24572093
TI  - Prestimulus frontal-parietal coherence predicts auditory detection performance in
      rats.
AB  - Electrophysiology in primates has implicated long-range neural coherence as a
      potential mechanism for enhancing sensory detection. To test whether local
      synchronization and long-range neural coherence support detection performance in
      rats, we recorded local field potentials (LFPs) in frontal and parietal cortex
      while rats performed an auditory detection task. We observed significantly
      elevated power at multiple low frequencies (<15 Hz) preceding the target beep
      when the animal failed to respond to the signal (misses), in both frontal and
      parietal cortex. In terms of long-range coherence, we observed significantly more
      frontal-parietal coherence in the beta band (15-30 Hz) before the signal on
      misses compared with hits. This effect persisted after regressing away linear
      trends in the coherence values during a session, showing that the excess frontal
      parietal beta coherence prior to misses cannot be explained by slow motivational
      changes during a session. In addition, a trend toward higher low-frequency (<15
      Hz) coherence prior to miss trials compared with hits became highly significant
      when we rereferenced the LFPs to the mean voltage on each recording array,
      suggesting that the results are specific to our frontal and parietal areas. These
      results do not support a role for long-range frontal-parietal coherence or local
      synchronization in facilitating the detection of external stimuli. Rather, they
      extend to long-range frontal-parietal coherence previous findings that correlate
      local synchronization of low-frequency (<15 Hz) oscillations with inattention to
      external stimuli and synchronization of beta rhythms (15-30 Hz) with voluntary or
      involuntary prolongation of the current cognitive or motor state. 

PMID- 24572094
TI  - Different phase delays of peripheral input to primate motor cortex and spinal
      cord promote cancellation at physiological tremor frequencies.
AB  - Neurons in the spinal cord and motor cortex (M1) are partially phase-locked to
      cycles of physiological tremor, but with opposite phases. Convergence of spinal
      and cortical activity onto motoneurons may thus produce phase cancellation and a
      reduction in tremor amplitude. The mechanisms underlying this phase difference
      are unknown. We investigated coherence between spinal and M1 activity with
      sensory input. In two anesthetized monkeys, we electrically stimulated the
      medial, ulnar, deep radial, and superficial radial nerves; stimuli were timed as
      independent Poisson processes (rate 10 Hz). Single units were recorded from M1
      (147 cells) or cervical spinal cord (61 cells). Ninety M1 cells were
      antidromically identified as pyramidal tract neurons (PTNs); M1 neurons were
      additionally classified according to M1 subdivision (rostral/caudal, M1r/c).
      Spike-stimulus coherence analysis revealed significant coupling over a broad
      range of frequencies, with the strongest coherence at <50 Hz. Delays implied by
      the slope of the coherence phase-frequency relationship were greater than the
      response onset latency, reflecting the importance of late response components for
      the transmission of oscillatory inputs. The spike-stimulus coherence phase over
      the 6-13 Hz physiological tremor band differed significantly between M1 and
      spinal cells (phase differences relative to the cord of 2.72 +/- 0.29 and 1.72 +/
      0.37 radians for PTNs from M1c and M1r, respectively). We conclude that
      different phases of the response to peripheral input could partially underlie
      antiphase M1 and spinal cord activity during motor behavior. The coordinated
      action of spinal and cortical feedback will act to reduce tremulous oscillations,
      possibly improving the overall stability and precision of motor control. 

PMID- 24572097
TI  - BDNF Val66Met polymorphism is associated with abnormal interhemispheric transfer
      of a newly acquired motor skill.
AB  - Recent data suggest that the Val66Met polymorphism of the brain-derived
      neurotrophic factor (BDNF) gene can alter cortical plasticity within the motor
      cortex of carriers, which exhibits abnormally low rates of cortical
      reorganization after repetitive motor tasks. To verify whether long-term
      retention of a motor skill is also modulated by the presence of the polymorphism,
      20 participants (10 Val66Val, 10 Val66Met) were tested twice at a 1-wk interval.
      During each visit, excitability of the motor cortex was measured by transcranial
      magnetic stimulations (TMS) before and after performance of a procedural motor
      learning task (serial reaction time task) designed to study sequence-specific
      learning of the right hand and sequence-specific transfer from the right to the
      left hand. Behavioral results showed a motor learning effect that persisted for
      at least a week and task-related increases in corticospinal excitability
      identical for both sessions and without distinction for genetic group. Sequence
      specific transfer of the motor skill from the right hand to the left hand was
      greater in session 2 than in session 1 only in the Val66Met genetic group.
      Further analysis revealed that the sequence-specific transfer occurred equally at
      both sessions in the Val66Val genotype group. In the Val66Met genotype group,
      sequence-specific transfer did not occur at session 1 but did at session 2. These
      data suggest a limited impact of Val66Met polymorphism on the learning and
      retention of a complex motor skill and its associated changes in corticospinal
      excitability over time, and a possible modulation of the interhemispheric
      transfer of procedural learning. 

PMID- 24572098
TI  - Monkeys time their pauses of movement and not their movement-kinematics during a
      synchronization-continuation rhythmic task.
AB  - A critical question in tapping behavior is to understand whether the temporal
      control is exerted on the duration and trajectory of the downward-upward hand
      movement or on the pause between hand movements. In the present study, we
      determined the duration of both the movement execution and pauses of monkeys
      performing a synchronization-continuation task (SCT), using the speed profile of
      their tapping behavior. We found a linear increase in the variance of pause
      duration as a function of interval, while the variance of the motor
      implementation was relatively constant across intervals. In fact, 96% of the
      variability of the duration of a complete tapping cycle (pause + movement) was
      due to the variability of the pause duration. In addition, we performed a
      Bayesian model selection to determine the effect of interval duration (450-1,000
      ms), serial-order (1-6 produced intervals), task phase (sensory cued or
      internally driven), and marker modality (auditory or visual) on the duration of
      the movement-pause and tapping movement. The results showed that the most
      important parameter used to successfully perform the SCT was the control of the
      pause duration. We also found that the kinematics of the tapping movements was
      concordant with a stereotyped ballistic control of the hand pressing the push
      button. The present findings support the idea that monkeys used an explicit
      timing strategy to perform the SCT, where a dedicated timing mechanism controlled
      the duration of the pauses of movement, while also triggered the execution of
      fixed movements across each interval of the rhythmic sequence. 

PMID- 24572101
TI  - How to estimate variability in affinity relationships in partially observed
      groups of domestic herbivores?
AB  - Animal sociability measurements based on inter-individual distances or nearest
      neighbour distributions can be obtained automatically with telemetry collars. So
      far, all the indices that have been used require the whole group to be observed.
      Here, we propose an index of the variability in affinity relationships in groups
      of domestic herbivores, whose definition does not depend on group size and that
      can be used even if some data are missing. This index and its estimators are
      based on a function that measures how frequently an animal is closer than another
      one from a third animal. When no data are missing, we show that our estimator and
      the variance of the sociability matrix sensu Sibbald (considered as the reference
      method) are strongly correlated. We then consider two cases of missing data. In
      the first case, some animals are randomly missing, that is, to account for random
      breakdown of telemetry collars. Our estimator is unbiased by such missing data
      and its variance decreases as the number of observation dates increases. In the
      second case, the same animals are missing at all observation dates, that is, in
      large herds where there are more individuals to be observed than available
      telemetry collars. Our estimator of affinity variance within a group is biased by
      such missing data. Thus, it requires changing animals equipped with telemetry
      collars regularly during the experiment. Conversely, the estimator remains
      unbiased at the population level, that is, if several independent groups are
      being analysed. We finally illustrate how this estimator can be used by
      investigating changes in the variability of affinities according to group size in
      grazing heifers. 

PMID- 24572102
TI  - [From greed research to grid research].

PMID- 24572099
TI  - Optical control of retrogradely infected neurons using drug-regulated "TLoop"
      lentiviral vectors.
AB  - Many approaches that use viral vectors to deliver transgenes have limited
      transduction efficiency yet require high levels of transgene expression. In
      particular, infection via axon terminals is relatively inefficient but is a
      powerful means of achieving infection of specific neuron types. Combining this
      with optogenetic approaches requires high gene expression levels that are not
      typically achieved with nontoxic retrogradely infecting vectors. We generated
      rabies glycoprotein-pseudotyped lentiviral vectors that use a positive feedback
      loop composed of a Tet promoter driving both its own tetracycline-dependent
      transcription activator (tTA) ("TLoop") and channelrhodopsin-2-YFP (ChR2YFP). We
      show that TLoop vectors strongly express proteins in a drug-controllable manner
      in neurons that project to injection sites within the mouse brain. After initial
      infection, the virus travels retrogradely, stably integrates into the host
      genome, and expresses gene products. The expression is robust and allows
      optogenetic studies of neurons projecting to the location of virus injection, as
      demonstrated by fluorescence-targeted intracellular recordings. ChR2YFP
      expression did not cause observable signs of toxicity and continued for up to 6
      mo after infection. Expression can be reversibly blocked by administration of
      doxycycline, if necessary, for expression of gene products that might be more
      toxic. Overall, we present a system that will allow researchers to achieve high
      levels of gene expression even in the face of inefficient viral transduction. The
      particular vectors that we demonstrate may enhance efforts to gain a precise
      understanding of the contributions of specific types of projection neurons to
      brain function. 

PMID- 24572103
TI  - [Neurons in motion: spinal networks controlling left-right alternation of walking
      movements deciphered by genetics].

PMID- 24572100
TI  - Quantitative cumulative biodistribution of antibodies in mice: effect of
      modulating binding affinity to the neonatal Fc receptor.
AB  - The neonatal Fc receptor (FcRn) plays an important and well-known role in
      antibody recycling in endothelial and hematopoietic cells and thus it influences
      the systemic pharmacokinetics (PK) of immunoglobulin G (IgG). However,
      considerably less is known about FcRn's role in the metabolism of IgG within
      individual tissues after intravenous administration. To elucidate the organ
      distribution and gain insight into the metabolism of humanized IgG1 antibodies
      with different binding affinities FcRn, comparative biodistribution studies in
      normal CD-1 mice were conducted. Here, we generated variants of herpes simplex
      virus glycoprotein D-specific antibody (humanized anti-gD) with increased and
      decreased FcRn binding affinity by genetic engineering without affecting antigen
      specificity. These antibodies were expressed in Chinese hamster ovary cell lines,
      purified and paired radiolabeled with iodine-125 and indium-111. Equal amounts of
      I-125-labeled and In-111-labeled antibodies were mixed and intravenously
      administered into mice at 5 mg/kg. This approach allowed us to measure both the
      real-time IgG uptake (I-125) and cumulative uptake of IgG and catabolites (In
      111) in individual tissues up to 1 week post-injection. The PK and distribution
      of the wild-type IgG and the variant with enhanced binding for FcRn were largely
      similar to each other, but vastly different for the rapidly cleared low-FcRn
      binding variant. Uptake in individual tissues varied across time, FcRn binding
      affinity, and radiolabeling method. The liver and spleen emerged as the most
      concentrated sites of IgG catabolism in the absence of FcRn protection. These
      data provide an increased understanding of FcRn's role in antibody PK and
      catabolism at the tissue level. 

PMID- 24572104
TI  - [Akkermansia muciniphila: a novel target controlling obesity, type 2 diabetes and
      inflammation?].

PMID- 24572105
TI  - [An allergic response to fight against venoms].

PMID- 24572106
TI  - [When microtubules meet clathrin-coated pits].

PMID- 24572107
TI  - [From centrosomes to microcephaly: follow the link].

PMID- 24572108
TI  - [Collectrin: a new component of the renin-angiotensin system?].

PMID- 24572110
TI  - [TSLP, the key of pruritus in atopic dermatitis].

PMID- 24572109
TI  - [From prion diseases to Alzheimer's disease: a common therapeutic target, PDK1].

PMID- 24572111
TI  - [Organization of interneurons lineages in the cerebral cortex].

PMID- 24572112
TI  - [Microglial cells and development of the embryonic central nervous system].
AB  - Microglia cells are the macrophages of the central nervous system with a crucial
      function in the homeostasis of the adult brain. However, recent studies showed
      that microglial cells may also have important functions during early embryonic
      central nervous system development. In this review we summarize recent works on
      the extra embryonic origin of microglia, their progenitor niche, the pattern of
      their invasion of the embryonic central nervous system and on interactions
      between embryonic microglia and their local environment during invasion. We
      describe microglial functions during development of embryonic neuronal networks,
      including their roles in neurogenesis, in angiogenesis and developmental cell
      death. These recent discoveries open a new field of research on the functions of
      neural-microglial interactions during the development of the embryonic central
      nervous system. 

PMID- 24572113
TI  - [Microglia: immune cells sculpting and controlling neuronal synapses].
AB  - The development of new animal models and functional analysis methods has
      dramatically changed our understanding of the physiology of microglial cells.
      These cells which are the resident macrophages of central nervous system have the
      ability to adapt rapidly to subtle changes of their environment. Recent findings
      indicate in particular that they can establish contacts with neuronal synapses
      that they can eliminate and modulate by releasing specific mediators. Here we
      review the experimental observations that have revealed the occurrence of these
      interactions not only in pathological conditions but also in the healthy brain
      and in particular during normal brain development. The discovery of bi
      directional communications between synapses and microglia sheds a new light on
      our understanding of brain functioning and should allow a better understanding of
      brain functioning and of interactions between immune and nervous systems. 

PMID- 24572114
TI  - [Interleukin-7, a new immunoadjuvant for the treatment of septic shock].
AB  - Sepsis-induced immunosuppression is a new paradigm in sepsis pathophysiology.
      This up-to-date review integrates recent facts in the field. It focuses on immune
      dysfunctions described so far in septic patients (especially regarding T
      lymphocytes), on the mechanisms sustaining this immune failure, on the monitoring
      of the pro-/anti-inflammatory balance rapidly changing over time and on new
      promising therapeutic avenues emerging from those recent findings. Of them, the
      case of interleukin-7 is more specifically envisaged. 

PMID- 24572115
TI  - [Neonatal tolerance to alloantigens].
AB  - In early life, our immune system has the characteristics of tolerance to
      alloantigens. During this period, our adaptive immunity is not at rest. On the
      contrary, it is polarized so as to promote the activation of Th2-type T cell
      response at the expense of cytotoxic Th1- or Th17-type responses. This may
      explain the vulnerability of infants to aggression by pathogens, their increased
      sensitivity to develop allergic diseases or their poor responses to some
      vaccines. Exposure to environmental factors will modify that neonatal tolerance
      due to its control by other actors and will thus have potential repercussions on
      the subsequent onset of allergies or autoimmune diseases.

PMID- 24572116
TI  - [The telomere position effect: silence in the back row!].
AB  - Heterochromatin displays repressive histone marks that down-regulate
      transcription. In the absence of specialized barriers, these repressive marks
      spread onto nearby nucleosomes and induce transcriptional silencing of these
      regions. Accordingly, in various species, transgenes that are experimentally
      inserted directly next to telomeric repeats are silenced. Transcriptional
      repression induced by the spreading of telomeric heterochromatin is known as the
      "telomere position effect". Although it is attenuated by the presence of natural
      subtelomeric barriers acting against the spreading of telomeric heterochromatin,
      telomere-induced silencing is also observed at the level of endogenous loci where
      it was initially proposed to provide a mean to regulate gene expression during
      senescence. This, however, remains to be formally demonstrated. Here, I review
      the current evidences for a telomere position effect, from yeast to human. 

PMID- 24572117
TI  - [Role of the prefrontal cortex in human behavioral adaptation].
AB  - Behavioral adaptation to complex or new situations depends on the anatomical,
      physiological and functional properties of the prefrontal cortex, and on its
      interaction with other regions. These properties allow distinguishing two main
      prefrontal regions: the lateral part involved in cognitive aspects of goal
      directed behaviors, and the ventral part involved in its affective aspects.
      Damage to these two regions is associated with two distinct clinical syndromes.
      Cognitive deficits in planning dominate in the lateral syndrome, behavioral
      regulation and motivation disorders in the ventral syndrome. Beyond this
      distinction, the question of how the systems that enable cognitive and behavioral
      aspects of adaptation are organized in prefrontal subregions, and can be best
      assessed, is not fully understood. This question is an essential issue in
      cognitive neuroscience and is crucial to improve clinical practice.

PMID- 24572118
TI  - [Targeted genome modifications using TALEN].
AB  - Precise modifications of genomes have been one of the biggest goals in the fields
      of biotechnology and biomedical research. Recent discovery of TALE (transcription
      activator-like effectors) and the engineering of customized TALEN (transcription
      activator-like effector nucleases) allowed rapid genome editing in a variety of
      cell types and different model organisms. TALEN are molecular scissors used to
      induce a wide range of specific and efficient genomic modifications. TALEN
      promise to have profound impacts on biological and medical research over the
      coming years. 

PMID- 24572119
TI  - [International teaching and training program in the international network of
      Pasteur Institutes].

PMID- 24572120
TI  - [2012 health national accounts: an apparent stability?].

PMID- 24572121
TI  - [Keys to the success of the CARMAT project?].

PMID- 24572122
TI  - [Reproductive medicine and the " desire for a child ": from normative judgment to
      conceptual analysis].
AB  - Reproductive medicine is widely discussed today in France, far beyond the borders
      of medical community. It is a topic of public controversy. The notion of "desire
      for a child" is very frequently referred to in this debate. It is wrongly
      considered as an obvious idea. A philosophical examination of the "desire for a
      child" allows us to elaborate a critical definition of it, cut from the normative
      judgments made about it. It highlights its double nature, being a desire linked
      to the private sphere as well as to public policies and social norms. It gives
      some reasons to understand how it became something that could be said and even
      claimed for in the public sphere. It examines the explanations that have been
      proposed about the desire for a child (its origin, the goal it fulfills). It
      proposes a frame of analysis based on a case-by-case approach and acknowledges as
      essential features of this desire its complexity, its ambiguous frontiers and its
      variability. The normative evaluation of the "desire for a child" cannot skip the
      phase of this conceptual analysis. 

PMID- 24572123
TI  - [Surprising results from Hiroshima studies].
AB  - One of the initial motivations for the Genome project was to improve the
      detection of possible mutations in children of atomic bomb survivors. In fact it
      has proved very difficult to find any genetic effect in these descendants in
      spite of the strong irradiation suffered by their parents: this factual evidence
      is largely ignored in the current debates about the effects of radiation and the
      future of nuclear energy. Sequencing studies on this population would be very
      desirable. 

PMID- 24572124
TI  - [After iPS, welcome to STAPs, a new reprogramming method].

PMID- 24572126
TI  - The biologic aspects of hydrotherapy.
AB  - The aquatic environment has a long and documented history in rehabilitation. This
      environment causes significant biologic effects which are applicable to many
      rehabilitative problems. Both immediate and delayed physiologic effects are noted
      in the immersed human and involve nearly all the basic homeostatic mechanisms.
      Particularly affected are the cardiovascular, renal, and pulmonary systems. The
      fundamental cardiovascular process is an increase in venous return with
      consequent increases in right atrial pressure, stroke volume, and cardiac output.
      The net effects upon the renal system are decreased anti-diuretic hormone (ADH)
      and aldosterone production, causing increased sodium and potassium excretion and
      consequent diuresis. The effects upon the respiratory system result from
      hydrostatic compression of the thorax coupled with increased intrathoracic blood
      volume. Both increase the work of breathing and decrease expiratory reserve
      volume. Effects upon muscle circulation, joint unloading, and general
      conditioning are also potentially useful in rehabilitation. This article reviews
      these effects and the literature support for these biologic changes. 

PMID- 24572125
TI  - Home-based oral immunotherapy (OIT) with an intermittent loading protocol in
      children unlikely to outgrow egg allergy.
AB  - BACKGROUND: Home based oral immunotherapy (OIT) for food allergy has often been
      used for young children in Japan, the majority of whom are believed to outgrow
      the allergy by the school age, therefore the true efficacy of the therapy has
      been controversial. The aim of this study was to evaluate the efficacy and safety
      of a newly developed slow- type home-based oral immunotherapy (OIT) regimen in
      children with hen's egg (HE) allergy, who had low likelihood of outgrowing the
      allergy, with treatment involving only elimination diet. METHOD: We
      retrospectively reviewed the medical records of 43 children with egg allergy (30
      males; median age 6) who fulfilled Burks et al.'s criteria of being unlikely to
      outgrow the allergy. Thirty children who agreed to start OIT were assigned to the
      treatment group, and 13 who did not want to participate immediately were assigned
      to the untreated group; the patients underwent an elimination diet for 1 year,
      during which they were monitored. The OIT regimen involved the intake of the
      maximum tolerated dose 2 to 3 times a week at home, with initial dose
      introduction followed by dose build-ups with medical supervision. We
      statistically evaluated the rate of children who changed their threshold up to 32
      g of egg - defined as, oral tolerance induction- in both the groups for 1 year
      and in the OIT group for 2 years, as well as the rate of children who fulfilled
      Savage et al.'s criteria of clinical tolerance after reaching the abovementioned
      remission stage. RESULTS: The rate of children who achieved oral tolerance
      induction to 32 g of egg after 1 year in the OIT group (9/30) was significantly
      higher than that in the untreated group (0/13). The total rate within the OIT
      group was significantly increased from 9/30 at 1 year to 17/30 at two years
      without any severe adverse reaction; of the above 17 children, we followed 14
      children, and noted that 11 of these were able to obtain clinical tolerance.
      CONCLUSION: The home-based OIT with an intermittent loading protocol was very
      safe and effective in children with a low likelihood of outgrowing egg allergy.

PMID- 24572127
TI  - Aquatics: risk management strategies for the therapy pool.
AB  - Risk management planning for employees and owners providing therapy services in
      the aquatic environment is preventive medicine. Being familiar with regulations,
      codes, operations, maintenance, contraindications, and appropriate personal
      safety in and around the therapy pool is essential for a safe environment for
      both patients and staff. 

PMID- 24572128
TI  - Spine pain: aquatic rehabilitation strategies.
AB  - Aquatic rehabilitation and swimming programs have been designed to treat spinal
      pain and dysfunction. They may be used in conjunction with land-based
      rehabilitation protocols or as the sole rehabilitative tool. The effectiveness of
      these programs requires the treating physician and therapist to have a thorough
      understanding of spinal anatomy, biomechanics, and pathophysiology as well as
      that of its associated kinetic chain. This understanding ensures that the primary
      dysfunction and any associated deficits are completely identified and treated.
      Aquatic programs can then be customized to address these dysfunctions and
      deficits thus helping to more rapidly minimize pain and maximize function. 

PMID- 24572129
TI  - Fundamentals and techniques of aqua running for athletic rehabilitation.
AB  - Aqua running is an effective form of cardiovascular conditioning for both injured
      athletes and those who desire a low-impact aerobic workout. Sufficient
      cardiovascular responses have been demonstrated to result in a training effect.
      Understanding the bioengineering principles of the aquatic environment, proper
      technique, physiological response, and methods of exercise prescription help
      practitioners incorporate aqua running into rehabilitation and training programs.

PMID- 24572130
TI  - Aquatic rehabilitation for the treatment of neurological disorders.
AB  - Patients with neurological disorders present therapists with complex challenges
      for treatment, including weakness, hypertonicity, voluntary movement deficit,
      limited range of motion, sensory loss, incoordination, and postural instability.
      The presence of one or more of these impairments negatively influences these
      patients by contributing to problems in walking, transferring, and reaching.
      Aquatic rehabilitation offers a unique, versatile approach to the treatment of
      these disabilities. This article examines the problems encountered by patients
      with neurological disorders, general principles guiding neurotreatment, and
      aquatic neurorehabilitation approaches. 

PMID- 24572131
TI  - Asthma, exercise-induced asthma, and aquatic physical activities.
AB  - Swimming is probably the most universal and healthiest sport, being practiced by
      individuals of all ages, either for leisure or to promote health. Compared to
      other types of physical activities (land based), swimming and other aquatic
      exercises are less likely to cause an asthmatic attack, often called exercise
      induced asthma, or EIA. Asthmatics and other chronic respiratory patients are
      often advised to swim in order to improve their fitness and ameliorate their
      symptoms. This article discusses the relationship between aquatic exercise and
      asthma, and provides practical clinical guidelines for the use of swimming and
      other water-based physical activities. 

PMID- 24572132
TI  - Overview of non-swimming aquatic research.
AB  - Research from 1967 through 1994 on non-swimming aquatic exercise has been
      reviewed to determine the physiologic parameters involved. The literature is
      replete with studies that deal with swimming but few have demonstrated the
      efficacy of non-swimming activity in an aquatic environment. The results of the
      review indicate that aquatic exercise performed in warm water-given the proper
      parameters of warm-up, intensity, duration, frequency, mode of training, and cool
      down-can influence maximal oxygen consumption, heart rate at rest and during
      exercise, upper body strength, and muscular endurance. It has also been noted
      that there is a paucity of clinical studies; therefore the need for application
      of this physiologic data appears paramount. As more clinical studies are
      performed, physicians can feel confident in referring their patients to aquatic
      physical therapists and other licensed professionals. 

PMID- 24572133
TI  - Swimming onward: the future of aquatic rehabilitation.
AB  - This article is a summary of the current state of the art in aquatic
      rehabilitation. It discusses affordable treatment modalities to enhance
      compliance. Fundamental research is lacking in aquatic rehabilitation as well as
      the availability of trained resource people. There is much to be gained through
      further development of aquatic methods, facilities, and communication pathways
      between medical professionals and the external world of aquatic community-based
      activities. 

PMID- 24572134
TI  - Annual index 1994.

PMID- 24572136
TI  - Back to water (or hydrotherapy).

PMID- 24572137
TI  - From the editor.

PMID- 24572138
TI  - Introduction.

PMID- 24572139
TI  - Intensive, progressive exercise improves quality of life following lumbar
      microdiskectomy: a randomized controlled trial.
AB  - OBJECTIVE: The purpose of the study was to examine changes in quality of life
      measures in patients who have undergone an intensive exercise program following a
      single level microdiskectomy. DESIGN: Randomized controlled trial with blinded
      examiners. SETTING: The study was conducted in outpatient physical therapy
      clinics. SUBJECTS: Ninety-eight participants (53 male, 45 female) who had
      undergone a single-level lumbar microdiskectomy allocated to receive exercise and
      education or education only. INTERVENTIONS: A 12-week periodized exercise program
      of lumbar extensor strength and endurance training, and mat and upright
      therapeutic exercises was administered. OUTCOME MEASURES: Quality of life was
      tested with the Short Form 36 (SF-36). Measurements were taken 4-6 weeks
      postsurgery and following completion of the 12-week intervention program. Since
      some participants selected physical therapy apart from the study, analyses were
      performed for both an as-randomized (two-group) design and an as-treated (three
      group) design. RESULTS: In the two-group analyses, exercise and education
      resulted in a greater increase in SF-36 scales, role physical (17.8 vs. 12.1) and
      bodily pain (13.4 vs. 8.4), and the physical component summary (13.2 vs. 8.9). In
      the three-group analyses, post-hoc comparisons showed exercise and education
      resulted in a greater increase in the SF-36 scales, physical function (10.4 vs.
      5.6) and bodily pain (13.7 vs. 8.2), and the physical component summary (13.7 vs.
      8.9) when compared with usual physical therapy. CONCLUSIONS: An intensive,
      progressive exercise program combined with education increases quality of life in
      patients who have recently undergone lumbar microdiskectomy.

PMID- 24572140
TI  - Service users' views of the assessment process in stroke rehabilitation.
AB  - OBJECTIVE: To investigate the service users' (stroke survivors and care-givers)
      experiences and views of the rehabilitation assessment process. DESIGN:
      Qualitative data analysis from three focus groups using a content analysis to
      identify the major themes. SETTING: Participants were recruited from stroke
      support groups and community rehabilitation services in a large UK city.
      SUBJECTS: Seventeen community-dwelling stroke survivors who had completed their
      rehabilitation within the previous year and six care-givers. RESULTS: Five themes
      emerged: understanding the purpose of the assessment; repetition of assessments;
      feedback about assessments and progress; format of feedback and barriers to
      feedback. While all participants reported undergoing assessment, some felt their
      purpose was not always explained and resented unexplained repetitions of tests.
      Some participants reported a positive experience, but most wanted more
      information about their progress and predictions of recovery. They wanted
      regular, consistent, objective information presented in layman's terms; verbally
      and in writing. Some carers reported difficulty accessing information
      particularly as a result of confidentiality policies. While some participants
      accepted these short-comings, others considered them due to staff's disinterest
      or ineptitude, which undermined their trust in the team. CONCLUSIONS: Stroke
      service users require clear information about the purpose of assessments and
      regular, consistent, objective feedback about their progress using layman's
      language both verbally and in writing.

PMID- 24572141
TI  - Epigenetic modification of MiR-429 promotes liver tumour-initiating cell
      properties by targeting Rb binding protein 4.
AB  - OBJECTIVE: Liver tumour-initiating cells (T-ICs) are critical for
      hepatocarcinogenesis. However, the underlying mechanism regulating the function
      of liver T-ICs remains unclear. METHODS: Tissue microarrays containing 242
      hepatocellular carcinoma (HCC) samples were used for prognostic analysis.
      Magnetically activated cell sorting was used to isolate epithelial cell adhesion
      molecule (EPCAM)-positive cells. The gene expressions affected by miR-429 were
      determined by arrays. Co-immunoprecipitation was used to study interactions among
      retinoblastoma protein (RB1), Rb binding protein 4 (RBBP4) and E2F transcription
      factor 1 (E2F1). The DNA methylation status in CpG islands was detected by
      quantitative methylation analysis. miRNAs in microvesicles were isolated by a
      syringe filter system. RESULTS: The significant prognosis factor miR-429 was
      upregulated in HCC tissues and also in primary liver T-ICs isolated from clinical
      samples. The enrichment of miR-429 in EPCAM+ T-ICs contributed to hepatocyte self
      renewal, malignant proliferation, chemoresistance and tumorigenicity. A novel
      functional axis involving miR-429, RBBP4, E2F1 and POU class 5 homeobox 1 (POU5F1
      or OCT4) governing the regulation of liver EPCAM+ T-ICs was established in vitro
      and in vivo. The molecular mechanism regulating miR-429 expression, involving
      four abnormal hypomethylated sites upstream of the miR-200b/miR-200a/miR-429
      cluster, was first defined in both EPCAM+ liver T-ICs and very early-stage HCC
      tissues. miR-429 secreted by high-expressing cells has the potential to become a
      proactive signalling molecule to mediate intercellular communication.
      CONCLUSIONS: Epigenetic modification of miR-429 can manipulate liver T-ICs by
      targeting the RBBP4/E2F1/OCT4 axis. This miRNA might be targeted to inactivate T
      ICs, thus providing a novel strategy for HCC prevention and treatment.

PMID- 24572142
TI  - XIAP variants in male Crohn's disease.
AB  - OBJECTIVE: The genetic basis of inflammatory bowel disease (IBD) is incompletely
      understood. The aim of this study was to identify rare genetic variants involved
      in the pathogenesis of IBD. DESIGN: Exome sequencing and immunological profiling
      were performed in a patient with early onset Crohn's disease (CD). The coding
      region of the gene encoding X-linked inhibitor of apoptosis protein (XIAP) was
      sequenced in samples of 275 paediatric IBD and 1047 adult-onset CD patients. XIAP
      genotyping was performed in samples of 2680 IBD patients and 2864 healthy
      controls. Functional effects of the variants identified were investigated in
      primary cells and cultured cell lines. RESULTS: Our results demonstrate the
      frequent occurrence of private variants in XIAP in about four percent of male
      patients with paediatric-onset CD. While XIAP mutations are known to be
      associated with the primary immunodeficiency (PID) X-linked lymphoproliferative
      disease type 2 (XLP2), CD patients described here exhibited intestinal
      inflammation in the absence of XLP2 and harboured a spectrum of mutations
      partially distinct from that observed in XLP2. The majority of XIAP variants
      identified was associated with a selective defect in NOD1/2 signalling, impaired
      NOD1/2-mediated activation of NF-kappaB, and altered NF-kappaB-dependent cytokine
      production. CONCLUSIONS: This study reveals the unanticipated, frequent
      occurrence of XIAP variants in male paediatric-onset CD. The link between XIAP
      and NOD1/2, and the association of XIAP variants with XLP2, support the concept
      of PID in a subset of IBD patients. Moreover, these studies provide a rationale
      for the implementation of XIAP sequencing in clinical diagnostics in male
      patients with severe CD.

PMID- 24572143
TI  - The human squamous oesophagus has widespread capacity for clonal expansion from
      cells at diverse stages of differentiation.
AB  - OBJECTIVE: Knowledge of the cellular mechanisms involved in homeostasis of human
      squamous oesophagus in the steady state and following chronic injury is limited.
      We aimed to better understand these mechanisms by using a functional 3D approach.
      DESIGN: Proliferation, mitosis and the expression of progenitor lineage markers
      were assessed in normal squamous oesophagus from 10 patients by
      immunofluorescence on 3D epithelial whole mounts. Cells expressing differential
      levels of epithelial and progenitor markers were isolated using flow cytometry
      sorting and characterised by qPCR and IF. Their self-renewing potential was
      investigated by colony forming cells assays and in vitro organotypic culture
      models. RESULTS: Proliferation and mitotic activity was highest in the
      interpapillary basal layer and decreased linearly towards the tip of the papilla
      (p<0.0001). The orientation of mitosis was random throughout the basal layer, and
      asymmetric divisions were not restricted to specific cell compartments. Cells
      sorted into distinct populations based on the expression of epithelial and
      progenitor cell markers (CD34 and EpCAM) showed no difference in self-renewal in
      2D culture, either as whole populations or as single cells. In 3D organotypic
      cultures, all cell subtypes were able to recapitulate the architecture of the
      tissue of origin and the main factor determining the success of the 3D culture
      was the number of cells plated, rather than the cell type. CONCLUSIONS:
      Oesophageal epithelial cells demonstrate remarkable plasticity for self-renewal.
      This situation could be viewed as an ex vivo wounding response and is compatible
      with recent findings in murine models.

PMID- 24572144
TI  - Automatic counting and positioning of 5-bromo-2-deoxyuridine (BrdU) positive
      cells in cortical layers of rat brain slices.
AB  - 5-Bromo-2-deoxyuridine (BrdU) staining is often used to evaluate cortical layer
      formation during mammalian brain development. This method allows the
      quantification of newly generated cells and therefore the study of the effects of
      xenobiotics or genetic factors on proliferation, cell death and migration
      behavior in a quantitative manner. However, these endpoints are generally
      assessed by time-consuming manual evaluation. In the present work, we introduce a
      novel procedure to identify and quantify BrdU(+) cells within cortical layers,
      using the commercially available vHCS-Scan V.6.3.1 software to identify BrdU(+)
      cell coordinates and the novel program 'BrdeLuxe' to define cortical layers and
      quantitatively assign BrdU(+) cells to them. This procedure is compared to
      BrdU(+) cell counting with the freeware 'ImageJ' in respect to the manual
      evaluation, all by two different researchers. BrdeLuxe shows high accuracy and
      precision for the determination of total number of BrdU(+) cells compared to the
      manual counting, while ImageJ does not reach such results. Accuracy and precision
      are also higher for employing the BrdeLuxe program to evaluate the percentage of
      BrdU(+) cells per brain layer compared to ImageJ. In terms of running time,
      BrdeLuxe is the fastest method of the three making it more suitable for multiple
      brain slices analyses. 

PMID- 24572145
TI  - Magnetic heterogeneous catalytic ozonation: a new removal method for phenol in
      industrial wastewater.
AB  - In this study, a new strategy in catalytic ozonation removal method for
      degradation of phenol from industrial wastewater was investigated. Magnetic
      carbon nano composite as a novel catalyst was synthesized, characterized and then
      used in the catalytic ozonation process (COP) and compared with the single
      ozonation process (SOP). The influential parameters were all investigated. The
      results showed that the removal efficiency of phenol and COD (chemical oxygen
      demand) in COP (98.5%, 69.8%) was higher than those of SOP (78.7%, 50.5%) and the
      highest catalytic potential was achieved at optimal neutral pH. First order
      modeling demonstrated that the reactions were dependent on the concentration of
      catalyst, with kinetic constants varying from 0.023 1/min (catalyst = 0 g/L) to
      0.071 1/min (catalyst = 4 g/L), whereby the optimum dosage of catalyst was found
      to be 2 g/L. Furthermore, the catalytic properties of the catalyst remained
      almost unchanged after 5-time reuse. The results regarding the biodegradability
      of the effluent showed that a 5-min reaction time in COP reduced the
      concentrations of phenol and COD to the acceptable levels for the efficient post
      treatment in the SBR in a 4-h cycle period. Finally, this combined system is
      proven to be a technically effective method for treating phenolic contaminants. 

PMID- 24572147
TI  - A new dielectric ta-C film coating of Ag-nanoparticle hybrids to enhance TiO2
      photocatalysis.
AB  - We have demonstrated a novel method to enhance TiO2 photocatalysis by adopting a
      new ultrathin tetrahedral-amorphous-carbon (ta-C) film coating on Ag
      nanoparticles to create strong plasmonic near-field enhancement. The result shows
      that the decomposition rate of methylene blue on the Ag/10 A ta-C/TiO2 composite
      photocatalyst is ten times faster than that on a TiO2 photocatalyst and three
      times faster than that on a Ag/TiO2 photocatalyst. This can be ascribed to the
      simultaneous realization of two competitive processes: one that excites the
      surface plasmons (SPs) of the ta-C-film/Ag-nanoparticle hybrid and provides a
      higher electric field near the ta-C/TiO2 interface compared to Ag nanoparticles
      alone, while the other takes advantage of the dense diamond-like ta-C layer to
      help reduce the transfer of photogenerated electrons from the conduction band of
      TiO2 to the metallic surface, since any electron transfer will suppress the
      excitation of SP modes in the metal nanoparticles.

PMID- 24572146
TI  - Neurogenic potential of dental pulp stem cells isolated from murine incisors.
AB  - INTRODUCTION: Interest in the use of dental pulp stem cells (DPSC) to enhance
      neurological recovery following stroke and traumatic injury is increasing
      following successful pre-clinical studies. A murine model of autologous neural
      stem cell transplantation would be useful for further pre-clinical investigation
      of the underlying mechanisms. However, while human-derived DPSC have been well
      characterised, the neurogenic potential of murine DPSC (mDPSC) has been largely
      neglected. In this study we demonstrate neuronal differentiation of DPSC from
      murine incisors in vitro. METHODS: mDPSC were cultured under neuroinductive
      conditions and assessed for neuronal and glial markers and electrophysiological
      functional maturation. RESULTS: mDPSC developed a neuronal morphology and high
      expression of neural markers nestin, betaIII-tubulin and GFAP. Neurofilament M
      and S100 were found in lower abundance. Differentiated cells also expressed
      protein markers for cholinergic, GABAergic and glutaminergic neurons, indicating
      a mixture of central and peripheral nervous system cell types. Intracellular
      electrophysiological analysis revealed the presence of voltage-gated L-type Ca2+
      channels in a majority of cells with neuronal morphology. No voltage-gated Na+ or
      K+ currents were found and the cultures did not support spontaneous action
      potentials. Neuronal-like networks expressed the gap junction protein, connexin
      43 but this was not associated with dye coupling between adjacent cells after
      injection of the low-molecular weight tracers Lucifer yellow or Neurobiotin. This
      indicated that the connexin proteins were not forming traditional gap junction
      channels. CONCLUSIONS: The data presented support the differentiation of mDPSC
      into immature neuronal-like networks.

PMID- 24572148
TI  - Acculturation and Health of Korean American Adults.
AB  - Increasing cultural diversity in the United States and significant health
      disparities among immigrant populations make acculturation an important concept
      to measure in health research. The purpose of this cross-sectional, descriptive
      study was to examine acculturation and health of Korean American adults. A
      convenience sample of 517 Korean American adults in a Midwestern city completed a
      survey in either English or Korean. All four groups of Berry's acculturation
      model were identified using cluster analysis with Lee's Acculturation Scale.
      Assimilation, integration, and separation were found in the English survey
      sample, whereas integration, separation, and marginalization were found in the
      Korean survey sample. Moreover, the findings revealed that acculturation is a
      bidimensional process, and the unique nature of samples may determine
      acculturation groups. Physical health and mental health were significantly
      related to acculturation in the English survey sample. However, there was not a
      significant relationship between health and acculturation in the Korean survey
      sample. 

PMID- 24572149
TI  - Spirituality, religiosity, and personal beliefs of Australian undergraduate
      nursing students.
AB  - PURPOSE: To explore Australian nursing students' perceptions of spirituality,
      religiosity, and personal belief. BACKGROUND: Spiritual and religious literature
      support the benefits to patients' physical and mental health. Nurses have an
      ethical obligation to understand and incorporate patient's spiritual beliefs and
      values into the care plan. METHOD: A cross-sectional survey was conducted using
      the 32-item WHO-QOL-SRPB questionnaire. SAMPLE: The sample consisted of 483
      undergraduate nursing students in Sydney, Australia. RESULTS: There were 21% male
      and 79% female students; age ranged from 18 to 56 years, with a mean age of 26.53
      (SD = 7.32). There were no significant difference between male and female nursing
      students, but there were difference in SRPB scores between first-, second-, and
      third-year students and between religious affiliations. CONCLUSIONS AND
      IMPLICATIONS: Spirituality is multidimensional and multilevel and is
      interconnected with religiosity and personal belief. Nurses need to understand
      their own spirituality before they can incorporate spirituality in their patient
      care.

PMID- 24572150
TI  - Self-management of type 2 diabetes: perspectives of Vietnamese Americans.
AB  - The purpose of this study was to explore diabetes self-management strategies and
      underpinnings of behaviors among Vietnamese with type 2 diabetes. Using
      Leventhal's illness representation model, semistructured interviews were
      conducted with a convenience sample of 23 participants, 14 women and 9 men. NVivo
      8 software was used for content analysis. Data revealed that participants
      constructed implicit theories of the identity, causes, consequences, timeline,
      and controllability of diabetes, which were inconsistent with the biomedical
      literature. Participants labeled diabetes by their symptoms of hypo
      /hyperglycemia, and they focused on the relief of these symptoms. However, the
      participants' focus on symptomatology undermined their use of blood glucose
      monitoring to manage diabetes as a majority of the participants had diabetes
      related complications. Participants integrated the continuum of Eastern and
      Western treatment belief systems to achieve a balance to create harmony between
      the two systems. 

PMID- 24572153
TI  - From the editor.

PMID- 24572154
TI  - The platinum league (tennis players don't ever stop playing).

PMID- 24572151
TI  - High glucose induces human endothelial dysfunction through an Axl-dependent
      mechanism.
AB  - BACKGROUND: The receptor tyrosine kinase Axl and its ligand growth arrest
      specific protein 6 (Gas6) are involved in the diabetic vascular disease. The aim
      of this study was to explore the role of Gas6/Axl system in high glucose (HG)
      induced endothelial dysfunction. METHODS: We investigated the effect of various
      glucose concentrations on Axl signaling in human microvascular endothelial cells
      (HMEC-1 s). RESULTS: Human plasma Gas6 value inversely correlated with glucose
      status, endothelial markers. HG decreased Gas6/Axl expression and increased
      intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1
      (VCAM-1) expression in HMEC-1 s. HG significantly decreased HMEC-1 s cell
      viability and tube formation and promoted monocyte-EC adhesion. Down-regulation
      of Akt phosphorylation was found in HG culture. Axl transfection significantly
      reversed HG-induced Akt phosphorylation, VCAM-1 expression and endothelial
      dysfunction. We also found additive changes in Axl-shRNA-infected HMEC-1 cells in
      HG culture. Furthermore, Axl overexpression in HMEC-1 s significantly reversed HG
      induced vascular endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR2)
      expression. In addition, significantly lower Axl and VEGFR2 expression in
      arteries were found in diabetic patients as compared with non-diabetic patients.
      CONCLUSIONS: This study demonstrates that HG can alter Gas6/Axl signaling and may
      through Akt and VEGF/VEGFR2 downstream molecules and suggests that Gas6/Axl may
      involve in HG-induced EC dysfunction.

PMID- 24572152
TI  - GraTeLPy: graph-theoretic linear stability analysis.
AB  - BACKGROUND: A biochemical mechanism with mass action kinetics can be represented
      as a directed bipartite graph (bipartite digraph), and modeled by a system of
      differential equations. If the differential equations (DE) model can give rise to
      some instability such as multistability or Turing instability, then the bipartite
      digraph contains a structure referred to as a critical fragment. In some cases
      the existence of a critical fragment indicates that the DE model can display
      oscillations for some parameter values. We have implemented a graph-theoretic
      method that identifies the critical fragments of the bipartite digraph of a
      biochemical mechanism. RESULTS: GraTeLPy lists all critical fragments of the
      bipartite digraph of a given biochemical mechanism, thus enabling a preliminary
      analysis on the potential of a biochemical mechanism for some instability based
      on its topological structure. The correctness of the implementation is supported
      by multiple examples. The code is implemented in Python, relies on open software,
      and is available under the GNU General Public License. CONCLUSIONS: GraTeLPy can
      be used by researchers to test large biochemical mechanisms with mass action
      kinetics for their capacity for multistability, oscillations and Turing
      instability.

PMID- 24572155
TI  - Introduction.

PMID- 24572156
TI  - Athletic performance - must it decline with age?
AB  - Many individuals continue to exercise train and experience athletic success well
      into the eighth and ninth decades of their lives. This paper examines the
      interaction between aging and athletic performance with specific reference to how
      regular exercise training attenuates the decrements in performance typically
      attributed to the aging process. The importance of rehabilitation of
      musculoskeletal injuries to facilitate continued participation in athletics is
      also addressed. 

PMID- 24572157
TI  - Osteoporosis and the aging athlete.
AB  - Osteoporosis is a clinical syndrome of bone fragility resulting in fractures with
      minimal or no trauma. Bone strength is directly related to bone mass, therefore
      factors that influence bone mass will determine the subsequent risk of
      osteoporotic fracture. Estrogen loss at the menopause is the most common cause of
      osteoporosis. Factors that limit the process of bone formation during adolescence
      and early adulthood can interfere with reaching peak adult bone mass and thereby
      predispose to osteoporosis in later adult years. Bone remodeling (bone resorption
      followed by formation) during the early and mid-adult years may be altered by
      many diseases, medications and lifestyle (alcohol, inadequate exercise, low
      calcium intake), resulting in reduced bone mass and increased risk for
      osteoporotic fracture. Extremes of physical training can also cause bone loss in
      women athletes, and can be reversed by estrogen and adequate calcium intake. More
      research is needed to determine which forms of training optimize the effects of
      exercise on bone mass. 

PMID- 24572158
TI  - The aging knee.
AB  - The aging knee presents significant problems to the mature athlete who wishes to
      continue participation in sports. The meniscus is a key structure in the knee and
      an injury to it may open the door to progressive arthritic changes. Because of
      our appreciation of the importance of the menisci, treatment options are geared
      toward salvaging as much of the meniscus as possible. The anterior cruciate
      ligament is a frequently injured structure which is associated with meniscus
      tears, articular cartilage damage and progressive degenerative changes. Once an
      athlete develops degenerative arthritis of their knee, their treatment options
      are mainly limited to arthroscopic lavage and debridement or an osteotomy
      procedure. The new knowledge and treatment options have allowed physicians to
      increase their arsenal in their battle to keep the mature athlete participating
      in sports. 

PMID- 24572159
TI  - Application of quantitative and progressive exercise rehabilitation to patients
      with osteoarthritis of the knee.
AB  - Osteoarthritis (OA) is one of the most prevalent and disabling diseases in the
      elderly, a rapidly growing segment of the population. OA is typically treated
      with a combination of drugs and inactivity, with total joint arthroplasty as the
      final treatment alternative. This paper reviews the potential of a non-surgical
      intervention for patients with OA, namely exercise rehabilitation. Several types
      of exercise rehabilitation are considered: home exercise (HE), physical therapy
      (PT), cycle exercise (CE) and a new program, quantitative progressive exercise
      rehabilitation (QPER). The HE program demonstrated improvements in some
      physiological and functional variables; however, these improvements were minimal.
      PT had a greater effect than HE on quadriceps and hamstring muscle strength and
      endurance and functional performance; however, PT had no effect on muscle
      contraction speed. The QPER program improved motor unit activation, quadriceps
      and hamstring muscle strength and endurance, contraction speed and all aspects of
      functional performance. In addition, QPER, although not aerobic, improved
      cardiorespiratory fitness and maximal workrate of VO2. This program significantly
      reduced difficulty, dependency and pain (during rest, exercise and at night). It
      would appear that the therapy of choice would be QPER since it reduces symptoms,
      improves joint integrity and may lead to delays in arthroplasty. These changes
      could improve the quality of life of patients with OA, as well as other diseases,
      and reduce medical costs. 

PMID- 24572160
TI  - The aging athlete's spine.
AB  - This article deals with the problems associated with the spine in an aging
      athletic person or in an elderly person who may be interested in starting a
      sports activity. The anatomy and pathophysiology of the spine as regards aging is
      discussed, as are common diagnostic tests and physical examination procedures.
      Specific disorders such as spinal stenosis and radiculopathy are examined and
      special issues in various sports activities are described. 

PMID- 24572161
TI  - Stabilization exercises for the aging athlete.
AB  - This article describes the use of spine stabilization exercises for treating low
      back pain in the aging athlete. Spine stabilization exercises are appropriate for
      treating a variety of pathological conditions in the spine and can be effective
      during all phases of the rehabilitative process. The emphasis of spine
      stabilization exercises is on minimizing stress on the spine to gain optimal
      function. 

PMID- 24572162
TI  - Imaging of the shoulder in the aging athlete.
AB  - The radiologic work-up of shoulder pain in the aging athlete should be tailored
      to meet the needs and expectations of the patient and physician. The value of
      high quality plain radiographs cannot be over-emphasized. When a more
      sophisticated imagine is necessary, the choice between arthrography, ultrasound,
      or MRI imaging is not straightforward. Arthrography is an excellent test to
      demonstrate full rotator cuff tears. In competitive athletes, a more
      sophisticated look at the rotator cuff and adjacent structures may be desired,
      which can be satisfied by MR imaging. 

PMID- 24572163
TI  - Reflections of a seasoned physician athlete.
AB  - Many seasoned athletes are more prone to injury than their younger counterparts
      due to the effects of aging, lack of coaching, and long intervals between
      workouts ('weekend warriors'). This is compounded if the middle-aged athlete was
      not an athlete as a young adult and therefore lacks prior instruction in good
      training habits. The author reflects on his own recent injury and interactions
      with medical care providers. Advice for care-givers includes: (1) wasting no time
      in work-up if the odds of successful treatment depend on timely diagnosis; (2)
      remembering to inform the patient of what can be expected during diagnostic and
      treatment procedures; (3) not forgetting the psychological well-being of your
      athlete-patient, and remembering you are treating the person, not just an injury;
      (4) helping the athlete-patient stay in shape during recovery; (5) involving the
      athlete-patient in decisions about treatment options, based on a mutual
      understanding of goals; (6) not assuming the seasoned athlete lacks the same
      aspirations as the young adult athlete; and (7) helping the athlete prevent other
      injuries for which he might be at risk. 

PMID- 24572164
TI  - An aging athlete looks at the aging athlete.

PMID- 24572167
TI  - Publishers note.

PMID- 24572165
TI  - Reflections of a seasoned athlete.

PMID- 24572169
TI  - A new murine model to study musculoskeletal tuberculosis (short communication).
AB  - Musculoskeletal tuberculosis (TB) is a severe extrapulmonary manifestation of
      chronic Mycobacterium (M.) tuberculosis infection. Considering increasing
      incidence, multi-drug resistance and associated treatment difficulties, more
      preclinical research is needed. In this study we developed a murine model for
      musculoskeletal TB. Mice, intranasally infected with M. tuberculosis, were
      sacrificed after ten months. Mycobacterial growth was detected in lung and femur
      homogenates. Ziehl-Neelsen staining of paraffin-embedded femurs showed acid-fast
      rods in the myelum and Magnetic Resonance Imaging demonstrated osteomyelitis and
      macronodular tuberculomas. This new murine model of musculoskeletal TB might be
      of value to further investigate immunologic and radiologic responses. 

PMID- 24572170
TI  - Effects of short-term oilseed supplementation on plasma fatty acid composition,
      progesterone and prostaglandin F metabolite in lactating beef cows.
AB  - Twenty-four 3-year-old Angus cows (512.2+/-21.6 kg) and six ruminally cannulated
      beef heifers (523.1+/-16.9 kg) were used to determine the impact of feeding
      oilseeds starting at the beginning of estrous synchronization until maternal
      recognition of pregnancy on plasma fatty acid composition. Starting ~60 days
      postpartum cows were synchronized with the Select Synch+controlled internal drug
      release (CIDR) device and timed artificial insemination (AI) protocol. The day
      CIDR was inserted; cattle were randomly assigned to one of the three treatments
      being grazing only (CON) or a supplement containing whole soybeans (SOY); or
      whole flaxseed (FLX). Cattle continued to receive these diets for 28 days. Blood
      was collected every 3 days until 10 days after insemination and then every day
      until 18 days after insemination. All cattle grazed a common pasture and
      supplemented cattle were individually fed their respective supplements once
      daily. Ruminally cannulated heifers were used to evaluate the impact supplements
      had on forage intake, which was reduced (P=0.05) with oilseed supplementation.
      Feeding oilseeds increased total fatty acid intake (P<0.001) across treatments
      with SOY having greater (P<0.001) 18:2n-6 intake than either CON or FLX.
      Likewise, cattle fed FLX had greater (P<0.001) 18:3n-3 intake than either CON or
      SOY. There was a treatment*time interaction (P<=0.05) for all fatty acids
      identified except for 20:5n-3 (P=0.99). Within 3 days after the start of
      supplementation, plasma concentrations of 18:2n-6 increased (P<0.001) for cattle
      fed SOY compared with CON or FLX, whereas flax-fed cattle did not exhibit an
      increase (P=0.02) until day 15 of supplementation over that of CON. Plasma
      concentrations for 18:3n-3 was greater (P<0.013) for FLX than both CON and SOY by
      day 12. Feeding flaxseed tended to (P=0.07) increase and increased (P=0.01)
      plasma concentrations of 20:4n-6 by day 18 over CON and SOY, respectively.
      Overall, treatment did not affect serum concentration of progesterone (P=0.18) or
      prostaglandin F metabolite (P=0.89). However, day after breeding had an effect on
      serum progesterone (P=0.01) with day 16 after timed AI being lower compared with
      other days. Feeding oilseeds during the time of estrous synchronization will not
      only increase the energy density of the diet but will provide key fatty acids
      around the time of maternal recognition of pregnancy.

PMID- 24572168
TI  - Non-tuberculous mycobacteria have diverse effects on BCG efficacy against
      Mycobacterium tuberculosis.
AB  - The efficacy of Bacillus Calmette-Guerin (BCG) vaccination in protection against
      pulmonary tuberculosis (TB) is highly variable between populations. One possible
      explanation for this variability is increased exposure of certain populations to
      non-tuberculous mycobacteria (NTM). This study used a murine model to determine
      the effect that exposure to NTM after BCG vaccination had on the efficacy of BCG
      against aerosol Mycobacterium tuberculosis challenge. The effects of
      administering live Mycobacterium avium (MA) by an oral route and killed MA by a
      systemic route on BCG-induced protection were evaluated. CD4+ and CD8+ T cell
      responses were profiled to define the immunological mechanisms underlying any
      effect on BCG efficacy. BCG efficacy was enhanced by exposure to killed MA
      administered by a systemic route; T helper 1 and T helper 17 responses were
      associated with increased protection. BCG efficacy was reduced by exposure to
      live MA administered by the oral route; T helper 2 cells were associated with
      reduced protection. These findings demonstrate that exposure to NTM can induce
      opposite effects on BCG efficacy depending on route of exposure and viability of
      NTM. A reproducible model of NTM exposure would be valuable in the evaluation of
      novel TB vaccine candidates. 

PMID- 24572171
TI  - The natural history of IgE mediated wheat allergy in children with dominant
      gastrointestinal symptoms.
AB  - BACKGROUND: Wheat is one of the most common food allergens in children. The
      purpose of this study is to define the natural course of wheat allergy in
      children with dominant gastrointestinal symptoms and identify factors that help
      predict development of tolerance. METHODS: The prospective analysis covered 50
      children with positive food challenge results (DBPCFC) and positive wheat IgE
      test result. Resolution of wheat allergy was determined on the basis of food
      challenge results (open challenge). The impact of each of the studied factors on
      the age when tolerance developed was assessed by means of the Cox proportional
      hazard regression model. RESULTS: The median age of tolerance development was
      69.5 months (37-192 mo.). The rates of resolution were 20% by the age of 4 years,
      52% by the age of 8 years, and 66% by 12 years, and 76% by 18 years. The median
      age of the tolerance development in children with peak wheat IgE level below10
      kU/L was 41.4 months, with peak wheat IgE from 10 to 19.9 kU/L was 44.5 months,
      with peak IgE from 20 to 49.9 kU/L - 84,9 months and with peak IgE >= 50 kU/L -
      190.5 months. The median of the age when the highest levels of IgE for wheat were
      reached was 33 months (2-52 mo.) in children with resolved wheat allergy and 67
      months (36-178 mo.) in children with persistent allergy (p = .001). CONCLUSIONS:
      1. The majority of children with wheat allergy can tolerate wheat by adolescence.
      2. The age when tolerance to wheat developed depended on the level and the age of
      reaching the highest levels of specific IgE for wheat. The higher the values of
      the above parameters, the older a child was when they developed tolerance to
      wheat.

PMID- 24572172
TI  - The competition between liquid and vapor transport in transpiring leaves.
AB  - In leaves, the transpirational flux of water exits the veins as liquid and
      travels toward the stomata in both the vapor and liquid phases before exiting the
      leaf as vapor. Yet, whether most of the evaporation occurs from the vascular
      bundles (perivascular), from the photosynthetic mesophyll cells, or within the
      vicinity of the stomatal pore (peristomatal) remains in dispute. Here, a one
      dimensional model of the competition between liquid and vapor transport is
      developed from the perspective of nonisothermal coupled heat and water molecule
      transport in a composite medium of airspace and cells. An analytical solution to
      the model is found in terms of the energy and transpirational fluxes from the
      leaf surfaces and the absorbed solar energy load, leading to mathematical
      expressions for the proportions of evaporation accounted for by the vascular,
      mesophyll, and epidermal regions. The distribution of evaporation in a given leaf
      is predicted to be variable, changing with the local environment, and to range
      from dominantly perivascular to dominantly peristomatal depending on internal
      leaf architecture, with mesophyll evaporation a subordinate component. Using
      mature red oak (Quercus rubra) trees, we show that the model can be solved for a
      specific instance of a transpiring leaf by combining gas-exchange data,
      anatomical measurements, and hydraulic experiments. We also investigate the
      effect of radiation load on the control of transpiration, the potential for
      condensation on the inside of an epidermis, and the impact of vapor transport on
      the hydraulic efficiency of leaf tissue outside the xylem. 

PMID- 24572173
TI  - Down-regulation of plasma intrinsic protein1 aquaporin in poplar trees is
      detrimental to recovery from embolism.
AB  - During their lifecycles, trees encounter multiple events of water stress that
      often result in embolism formation and temporal decreases in xylem transport
      capacity. The restoration of xylem transport capacity requires changes in cell
      metabolic activity and gene expression. Specifically, in poplar (Populus spp.),
      the formation of xylem embolisms leads to a clear up-regulation of plasma
      membrane protein1 (PIP1) aquaporin genes. To determine their role in poplar
      response to water stress, transgenic Populus tremula * Populus alba plants
      characterized by the strong down-regulation of multiple isoforms belonging to the
      PIP1 subfamily were used. Transgenic lines showed that they are more vulnerable
      to embolism, with 50% percent loss of conductance occurring 0.3 MPa earlier than
      in wild-type plants, and that they also have a reduced capacity to restore xylem
      conductance during recovery. Transgenic plants also show symptoms of a reduced
      capacity to control percent loss of conductance through stomatal conductance in
      response to drought, because they have a much narrower vulnerability safety
      margin. Finally, a delay in stomatal conductance recovery during the period of
      stress relief was observed. The presented results suggest that PIP1 genes are
      involved in the maintenance of xylem transport system capacity, in the promotion
      of recovery from stress, and in contribution to a plant's control of stomatal
      conductance under water stress. 

PMID- 24572174
TI  - Fasciola hepatica: effect of the natural light level on cercarial emergence from
      temperature-challenged Galba truncatula.
AB  - As abrupt changes in water temperature (thermal shock) triggered a significantly
      greater cercarial emergence of Fasciola hepatica from experimentally infected
      Galba truncatula, laboratory investigations were carried out to study the
      influence of light on cercarial emergence in snails subjected to a thermal shock
      every week (a mean of 12  degrees C for 3 h) during the patent period. Thermal
      shock for these temperature-challenged (TC) snails was carried out outdoors under
      artificial or natural light, or indoors under constant artificial light. Compared
      with the infected control snails always reared indoors at 20  degrees C, the
      number of cercariae in TC snails subjected to a thermal shock and natural light
      outdoors was significantly greater. The repetition of this experiment by
      subjecting TC snails to the same thermal shock indoors under an artificial light
      level ranging from 600 to 3000 lux did not show any significant difference among
      the numbers of cercariae in the different subgroups. A detailed analysis of the
      results noted in the TC snails subjected to natural light during the thermal
      shock demonstrated that the number of cercariae-releasing snails was
      significantly higher between 601 and 1200 lux and for the highest nebulosity
      values (7-8 octas, which corresponds to a sufficiently or completely overcast
      sky). Contrary to the intensity of artificial light, which did not influence
      cercarial emergence, the natural light level had a significant effect on this
      process when F. hepatica-infected snails were subjected to a regular thermal
      shock during the patent period.

PMID- 24572176
TI  - Rohdella amazonica n. sp. (Aspidogastrea: Aspidogastridae) from the Amazoninan
      banded puffer fish Colomesus psittacus (Bloch & Schneider, 1801).
AB  - Aspidogastreans are commonly found infecting freshwater and marine molluscs,
      teleosts fishes and freshwater turtles. The subclass comprises four families -
      Rugogastridae Schell 1973, Stichocotylidae Faust & Tang 1936, Multicalycidae
      Gibson & Chinabut 1984 and Aspidogastridae Poche 1907 - and it is characterized
      by the presence of a ventral adhesive disc divided into rows of alveoli. In the
      current work, using light and scanning electron microscopy and molecular
      approaches, a new species of Aspidogastridae of the genus Rohdella Gibson &
      Chinabut, 1984, is described as a parasite of Colomesus psittacus in Brazil. The
      new taxon is distinguishable by the presence of oesophageal glands, teguments
      covered by ciliated papillae, and the position and shape of the hermaphroditic
      duct. The present work describes the third species of the genus Rohdella, thereby
      adding new morphological and molecular data regarding Aspidogastridae. 

PMID- 24572175
TI  - Targeting FcRn for therapy: from live cell imaging to in vivo studies in mice.
AB  - The role of FcRn in regulating antibody levels and transport in the body is well
      documented. The use of fluorescence microscopy to investigate the subcellular
      trafficking behavior of FcRn and its IgG ligand has led to insight into the
      function of this receptor, including the identification of new intracellular
      pathways. The inhibition of FcRn using engineered antibodies that bind to this
      receptor with increased affinity through their Fc region can be exploited to
      treat antibody mediated autoimmunity. The efficacy of this approach in mouse
      models of arthritis and multiple sclerosis has been demonstrated. Finally, the
      cross-species difference between mouse and man for FcRn-IgG interactions needs to
      be considered when engineering antibodies for improved activities in FcRn
      mediated functions. 

PMID- 24572177
TI  - Expression of cathelicidins mRNA in the goat mammary gland and effect of the
      intramammary infusion of lipopolysaccharide on milk cathelicidin-2 concentration.
AB  - Cathelicidins are a family of antimicrobial peptides found in neutrophils and the
      epithelium that have broad-spectrum activity against bacteria. This study aimed
      to investigative the mRNA expression of cathelicidins and protein localization of
      cathelicidin-2 in the goat mammary gland and its secretion into milk. The mRNA
      expression of cathelicidins was examined in different regions of the mammary
      gland by reverse transcription PCR. A cathelicidin-2 antibody was raised in
      rabbits by immunization with a synthetic cathelicidin-2 peptide consisting of 17
      amino acids. The protein localization of cathelicidin-2 was investigated in the
      mammary gland by immunohistochemistry. Skim milk was collected before (0 h) and
      2, 4, 8, 12, and 24h after the intramammary infusion of lipopolysaccharide and
      saline, and the concentration of cathelicidin-2 was examined by an enzyme
      immunoassay. The mRNAs of cathelicidin-1, 2, 3, 6, and 7 were expressed in both
      the teat and deep region of the mammary gland from healthy and mastitic goats.
      Immunoreactive cathelicidin-2 was not localized in the epithelial cells of the
      teat skin, teat cistern, or mammary alveoli, whereas it was localized in
      polymorphonuclear cells in the mammary gland and those collected from the blood
      and milk. Cathelicidin-2 was detected in skim milk by Western blotting. The
      concentration of cathelicidin-2 in milk increased 4h after the intramammary
      infusion of lipopolysaccharide. These results suggest that cathelicidin-2 is
      expressed in polymorphonuclear cells and is secreted into milk in goat.

PMID- 24572178
TI  - Optimal care and design of the tracheal cuff in the critically ill patient.
AB  - Despite the increasing use of non-invasive ventilation and high-flow nasal-oxygen
      therapy, intubation is still performed in a large proportion of critically ill
      patients. The aim of this narrative review is to discuss recent data on long-term
      intubation-related complications, such as microaspiration, and tracheal ischemic
      lesions. These complications are common in critically ill patients, and are
      associated with substantial morbidity and mortality. Recent data suggest
      beneficial effects of tapered cuffed tracheal tubes in reducing aspiration.
      However, clinical data are needed in critically ill patients to confirm this
      hypothesis. Polyurethane-cuffed tracheal tubes and continuous control of cuff
      pressure could be beneficial in preventing microaspiration and ventilator
      associated pneumonia (VAP). However, large multicenter studies are needed before
      recommending their routine use. Cuff pressure should be maintained between 20 and
      30 cmH2O to prevent intubation-related complications. Tracheal ischemia could be
      prevented by manual or continuous control of cuff pressure. 

PMID- 24572187
TI  - Capitation combined with pay-for-performance improves antibiotic prescribing
      practices in rural China.
AB  - Pay-for-performance in health care holds promise as a policy lever to improve the
      quality and efficiency of care. Although the approach has become increasingly
      popular in developing countries in recent years, most policy designs do not
      permit the rigorous evaluation of its impact. Thus, evidence of its effect is
      limited. In collaboration with the government of Ningxia Province, a
      predominantly rural area in northwest China, we conducted a matched-pair cluster
      randomized experiment between 2009 and 2012 to evaluate the effects of capitation
      with pay-for-performance on primary care providers' antibiotic prescribing
      practices, health spending, outpatient visit volume, and patient satisfaction. We
      found that the intervention led to a reduction of approximately 15 percent in
      antibiotic prescriptions and a small reduction in total spending per visit to
      village posts-essentially, community health clinics. We found no effect on other
      outcomes. Our results suggest that capitation with pay-for-performance can
      improve drug prescribing practices by reducing overprescribing and inappropriate
      prescribing. Our study also shows that rigorous evaluations of health system
      interventions are feasible when conducted in close collaboration with the
      government.

PMID- 24572189
TI  - From the editor.

PMID- 24572190
TI  - Bifocals are a pain in the neck.

PMID- 24572188
TI  - A review of what is an emerging contaminant.
AB  - A review is presented of how one defines emerging contaminants and what can be
      included in that group of contaminants which is preferably termed "contaminants
      of emerging concern". An historical perspective is given on the evolution of the
      issues surrounding emerging contaminants and how environmental scientists have
      tackled this issue. This begins with global lead contamination from the Romans
      two millennia ago, moves on to arsenic-based and DDT issues and more recently to
      pharmaceuticals, cyanotoxins, personal care products, nanoparticles, flame
      retardants, etc. Contaminants of emerging concern will remain a moving target as
      new chemical compounds are continuously being produced and science continuously
      improves its understanding of current and past contaminants. 

PMID- 24572191
TI  - Physician limitations when assessing work capacity: a review.
AB  - Literature evidence indicates that physicians have great difficulty in
      translating medical impairment into functional limitation and thereby
      establishing the work capacity or the residual functional capacity (RFC) of the
      injured worker. This is especially true for the chronic pain patient (CPP).
      Development of quantitative methods for the measurement of functional capacity
      (FC), have not improved the problems involved in the measurement of RFC and the
      translation of RFC into the demand minimum functional capacity (DMFC) of some job
      or jobs. The relationship between FC, RFC, work capacity and DMFC is reviewed. We
      have developed a method/battery for measuring RFC in CPPs utilizing the
      Dictionary of Occupational Titles (DOT) which is readily translatable into DMFC
      of some job or jobs. Suggestions are made for future directions in the
      measurement of work capacity. 

PMID- 24572192
TI  - Clinical practice guidelines for chronic non-malignant pain syndrome patients.
AB  - The current paper provides specific guidelines for treating chronic non-malignant
      pain syndrome patients. The guidelines were developed from an extensive review of
      existing literature on practice guidelines, the research literature, and common
      clinical practice across major pain treatment facilities in the USA. They are
      intended for application to all chronic pain syndrome patients (other than cancer
      pain) regardless of specific site or etiology of pain. They advocate goal
      directed treatment to reduce medication misuse and invasive medical procedures,
      maximize and maintain physical activity, return to productive activity, increase
      the patient's ability to manage pain, reduce subjective pain intensity, reduce or
      eliminate the use of healthcare services for primary pain complaint, provide
      useful information for case settlement, and minimize treatment cost without
      sacrificing quality. The guidelines recommend interdisciplinary integrated
      evaluation and treatment on a time limit basis with a focus on conservative
      medical, psychological behavioral, physical, and vocational interventions based
      upon the patient's needs. There is emphasis on increasing the patient's level of
      function and ability to manage pain and related problems. Outpatient care is
      strongly recommended, with specific upper limits regarding treatment intensity
      and the use of trigger point injections and nerve blocks delineated. The
      guidelines also recommend that the long term use of opioid or sedative-hypnotic
      medications, surgery, implantable spinal devices, or brain stimulation techniques
      be avoided with chronic pain syndrome patients. These guidelines are intended to
      serve as a starting point to effectively extend and complement those released by
      the Agency for Health Care Policy and Research for other types of pain problems
      such as cancer and acute low back pain. 

PMID- 24572193
TI  - Common treatments for low back pain: have they been proven effective?
AB  - The etiology of low back pain can be complex and the specific etiologies are
      rarely separated for investigation. There continues to be no single clinically
      proven superior treatment for low back pain. This may explain the multiplicity of
      treatments available. The purpose of this article is to evaluate the different
      forms of treatment for low back pain, treatment outcome and effectiveness. Nine
      more common treatments for low back pain are described. The long term
      effectiveness of the procedures reviewed in this article for the treatment of low
      back pain remains doubtful. For the majority of patients with complaints of low
      back surgery is not indicated. For those patients who have neurological deficits
      and a documented lesion, surgery can be an immediate and appropriate treatment.
      The conventional treatment for low back pain continues to be the triad of rest,
      analgesic medication and perhaps exercise after the acute phase of low back pain.
      None of the other treatment options evaluated in this review were consistently
      shown to be more effective than this traditional triad treatment course. 

PMID- 24572194
TI  - The role of rehabilitation medicine in the management of chronic pain:
      description of a pain control program and longitudinal outcomes.
AB  - Longitudinal outcomes of 35 patients with chronic benign pain were studied
      following their participation in a 3-week multidisciplinary pain management
      program. Pretreatment status with respect to activity levels, health care
      utilization, medication use, and subjective pain intensity was compared
      statistically with post-treatment status at three follow-up assessments
      (discharge, 1.6 months, and 22.7 months post-discharge). Results suggest a
      positive impact of treatment on activity levels, health care utilization, and
      medication use post-discharge, with diminution of that impact over time. Pain
      management programs increasingly will need to demonstrate cost effectiveness,
      including finding ways to maximize program gains over time. 

PMID- 24572195
TI  - Types of cervical disc herniation and relation to myelopathy and radiculopathy.
AB  - Cervical disc herniation is divided into three types with respect to the
      intraspinal location of the herniated mass: median, paramedian and lateral
      herniations. Median herniation presses the spinal cord against the lamina and
      deforms it into a boomerang shape in a cross section, thereby giving rise to
      myelopathy of the central cord syndrome or transverse lesion syndrome, according
      to Crandall's classification. Paramedian herniation presses the spinal cord
      unilaterally and deforms it into a comma shape. The symptoms and signs produced
      are not always those of the Brown-Sequard syndrome. Radiculopathy is produced by
      compression of a root in patients with a wide spinal canal in which the spinal
      cord is thereby able to avoid compression. Lateral herniation presses a nerve
      root at the anterolateral corner of the spinal canal to the inlet of the foramen,
      thereby giving rise to radiculopathy. Of our 202 patients with myelopathy, 36%
      had median herniation and 64% had paramedian herniation. Of our 24 patients with
      radiculopathy, 12% had paramedian herniation and 88% had lateral herniation.
      Other matters pertinent to the management of patients are described. 

PMID- 24572196
TI  - Lumbar radiculopathy and intraspinal gas.
AB  - Gas within the spinal canal is uncommon and has been associated with trauma,
      infection and disc degeneration and vacuum phenomenon. We report a 73-year-old
      man with a history of intermittent low back pain who developed sharp low back
      pain with radiation to the left calf and ankle when ambulating or standing.
      Relief was obtained with sitting or lying down, which led to the clinical
      impression of spinal stenosis. The neuromuscular exam was unremarkable and no
      sciatic nerve tension sign was present. Electrodiagnostic studies were consistent
      with an acute S1 radiculopathy, while a dermatomal somatosensory evoked potential
      was interpreted as essentially normal. A CT scan showed gas in the left lateral
      spinal canal at L4-S1. After 2 weeks, spontaneous improvement occurred and the
      patient resumed normal activities. A repeat CT scan after 0.5 years showed the
      intraspinal gas was diminished while the L5-S1 disc vacuum phenomenon had
      worsened and a right disc extrusion occurred. The natural history of intraspinal
      gas, disc vacuum phenomenon and related complications are discussed. 

PMID- 24572197
TI  - Working with workers' compensation: one lawyer's opinion.

PMID- 24572198
TI  - The treating physician as expert witness.
AB  - Treating physicians frequently are called upon to offer expert testimony in
      litigation. Courts will usually require treating physicians to give testimony
      about the facts concerning-their treatment and care of the patient. Courts have
      reached varying conclusions as to the extent that a treating physician can be
      compelled to render opinions about the patient's condition and prognosis.
      Different jurisdictions have varying rules as to what compensation, if any, is
      required to be paid to a treating physician subpoenaed to testify in the absence
      of a contract between a physician and a party concerning such compensation.
      Testimony offered by treating physicians who qualify as medical experts must be
      found to be trustworthy by the court prior to being admitted into evidence. 

PMID- 24572199
TI  - Preparing medical legal reports and dealing with lawyers.
AB  - In preparing reports or records for patients in personal injuryThe term 'personal
      injury' includes cases involving automobile accidents, slip and falls, defective
      products and medical malpractice. litigation certain basic information will be
      necessary. Most of that information is often provided in the basic chart without
      the need for a written report. Ensure that when providing records or discussing
      the patient's care and treatment with an attorney that your are providing records
      in a timely manner to the attorney for the patient and that you are not
      discussing the case with counsel for your patient's opponent. When in doubt, call
      the patient's attorney and ask them what information is needed. 

PMID- 24572200
TI  - Radiologic 'clearance' of the traumatized cervical spine.
AB  - Rapid, thorough and cost effective radiologic evaluation of the traumatized spine
      can be performed through a tailored sequential approach. The radiologic
      evaluation is performed in conjunction with clinical management, and therefore
      communication between clinical and radiological services is essential. Judicious
      use of CT and MRI can provide critical information, particularly in the
      symptomatic patient with 'normal' radiographs. 

PMID- 24572203
TI  - The Impact of Hispanic Ethnicity on Knowledge and Behavior Among Patients With
      Diabetes.
AB  - PURPOSE: The purpose of the study was to measure the current level of awareness
      of the American Heart Association's 7 risk/protective factors of cardiovascular
      health among adults with diabetes of Hispanic and non-Hispanic origin and to
      identify factors associated with knowledge deficits. METHODS: A cross-sectional
      survey measured demographic data, personal behaviors/health factors,
      cardiovascular disease (CVD) history, and knowledge of 7 components of ideal
      cardiovascular health (smoking, obesity, exercise, diet, cholesterol, blood
      pressure, and blood glucose). A subset of 331 Hispanic and white patients with
      diabetes was surveyed. Knowledge scores were dichotomized between full knowledge
      (7 components) and less than full knowledge and compared between ethnicities
      using multiple logistic regression. RESULTS: Seventy-nine percent of surveys were
      returned; 50.5% of subjects were Hispanic. Median age was 64.5 years with 60.7%
      being female. Two-thirds of the sample completed high school and 26% reported
      comorbid CVD. Recognition of diabetes as a risk factor didn't differ by
      ethnicity. Thirty-five percent of respondents identified 7 American Heart
      Association risk factors. Hispanics were less likely to identify 7 components.
      After adjustment for education and English literacy, the difference disappeared.
      Better knowledge was positively associated with healthier behaviors for high
      cholesterol, hypertension, and exercise only among white patients. CONCLUSIONS:
      Hispanic patients with diabetes exhibit less knowledge about CVD risk/protective
      factors due to lower education and English literacy. Educational interventions
      should be tailored to those with less education/limited English proficiency.

PMID- 24572204
TI  - Toll-interacting protein modulates colitis susceptibility in mice.
AB  - BACKGROUND: The intestinal epithelium accommodates with a myriad of commensals to
      maintain immunological homeostasis, but the underlying mechanisms regulating
      epithelial responsiveness to flora-derived signals remain poorly understood.
      Herein, we sought to determine the role of the Toll/interleukin (IL)-1 receptor
      regulator Toll-interacting protein (Tollip) in intestinal homeostasis. METHODS:
      Colitis susceptibility was determined after oral dextran sulfate sodium (DSS)
      administration or by breeding Tollip on an IL-10 background. The intestinal flora
      was depleted with 4 antibiotics before DSS exposure to assess its contribution in
      colitis onset. Bone marrow chimeras were generated to identify the cellular
      compartment, whereby Tollip may negatively regulate intestinal inflammation in
      response to DSS. Tollip-dependent epithelial barrier functions were studied in
      vitro by using Tollip-knockdown in Caco-2 cells and in vivo by
      immunohistochemistry and fluorescein isothiocyanate-labeled dextran gavage.
      RESULTS: Genetic ablation of Tollip did not lead to spontaneous intestinal
      inflammatory disorders. However, Tollip deficiency aggravated spontaneous disease
      onset in IL-10 mice and increased susceptibility to DSS colitis. Increased
      colitis severity in Tollip-deficient mice was not improved by bacterial flora
      depletion using broad-spectrum antibiotics. In addition, DSS exposure of bone
      marrow chimeric mice revealed a protective role for Tollip in nonhematopoietic
      cells. Knockdown of Tollip in epithelial cells led to exaggerated NFkappa-B
      activity and proinflammatory cytokine secretion. Finally, DSS-treated Tollip mice
      showed enhanced intestinal permeability and increased epithelial apoptosis when
      compared with wild-type controls, a finding that coincided with tight junction
      alterations on injury. CONCLUSION: Overall, our data show an essential role for
      Tollip on colitis susceptibility in mice.

PMID- 24572205
TI  - Prevalence of anemia in inflammatory bowel diseases in european countries: a
      systematic review and individual patient data meta-analysis.
AB  - BACKGROUND: The main objective is to determine the overall prevalence of anemia
      in inflammatory bowel diseases (IBD) in Europe. METHODS: A systematic literature
      search in PubMed and Embase was performed for studies published between January
      2007 and May 2012. Eligible studies were included if they were original full
      paper publications originated from Europe and if the authors agreed to provide
      their data. An overall prevalence of anemia in IBD, disease specific, and age
      gender stratified basis prevalences were estimated. The influence of disease
      entity (Crohn's disease/ulcerative colitis), gender, age, disease activity
      (remission/active disease), and IBD-specific treatment strategies on the
      prevalence of anemia was analyzed by a mixed logistic regression model. Thereby,
      the factor country of origin was included as a random effect. RESULTS: Data were
      available for 2192 patients, mainly treated in tertiary referral centers. The
      overall prevalence of anemia in IBD patients was 24% (95% confidence interval, 18
      31). Age-gender stratified prevalences were estimated for the age strata 18 to
      29, 30 to 39, 40 to 49, 50 to 64, 65 to 74, >74 years and ranged from 18% to 35%.
      Patients receiving IBD-specific medication (P = 0.0002, odds ratio 1.54), and
      patients with active disease status (P < 0.0001, odds ratio 2.72) were
      significantly more likely to have anemia compared with patients not receiving IBD
      specific medication or being in remission. Patients with ulcerative colitis
      tended to have anemia less likely than patients with Crohn's disease (P = 0.01,
      odds ratio 0.77). CONCLUSIONS: The overall prevalence of anemia in patients with
      Crohn's disease was 27% (95% confidence interval, 19-35) and 21% (95% confidence
      interval, 15-27) in patients with ulcerative colitis. Thereby, 57% of the anemic
      patients were iron deficient.

PMID- 24572206
TI  - Stopping anti-TNF agents in patients with Crohn's disease in remission: is it a
      feasible long-term strategy?

PMID- 24572207
TI  - Colitis surveillance guidelines--which is best?

PMID- 24572208
TI  - Stem cells as potential targeted therapy for inflammatory bowel disease.
AB  - The incidence and prevalence of inflammatory bowel disease is increasing in
      Western countries. Current therapies, ranging from anti-inflammatory drugs,
      immunosuppressive regimens to new biological therapies, remain inadequate.
      Advances in our understanding of the pathophysiological mechanisms underlying the
      pathogenetic disease process and the recent findings on the regenerative and
      immunoregulatory potential of stem cells open new opportunities in the therapy of
      inflammatory bowel disease. Therapeutic modalities, including hematopoietic stem
      cells, adult mesenchymal stem/stromal cells, and the recently identified amniotic
      origin stem cells, attracted much attention in the recent years. The current
      review highlights the recent pivotal findings for stem cell-based approaches to
      inflammatory bowel disease therapy.

PMID- 24572209
TI  - Reply to Rutter.

PMID- 24572212
TI  - The plantar plate of the first metatarsophalangeal joint: an anatomical study.
AB  - The plantar plate of the first metatarsophalangeal (MP) joint is a critical
      structure of the forefoot that has been identified as a major stabilizer within
      the capsuloligamentous complex. Many studies have clarified and documented the
      anatomy of the lesser toe MP plantar plates, but few have looked closely at the
      anatomy of the first MP joint. Ten cadaveric specimens were examined to identify
      and document the objective anatomic relationship of the plantar plate, tibial
      sesamoid, and surrounding osseus structures. The average distance of the plantar
      plate distal insertion from the joint line into the proximal phalanx was 0.33 mm.
      The plantar plate was inserted into the metatarsal head on average 17.29 mm
      proximal from the joint line. The proximal aspect of the sesamoid was 18.55 mm
      proximal to the distal attachment of the plantar plate to the phalanx. The distal
      aspect of the sesamoid averaged 4.69 mm away from the distal attachment into the
      proximal phalanx. The footprint of the distal plate insertion was on average 6.33
      mm in length in the sagittal plane. The authors hope that these objective data
      measures can aid in the understanding and subsequent surgical repair of this
      important forefoot structure.

PMID- 24572210
TI  - Body adiposity dictates different mechanisms of increased coronary reactivity
      related to improved in vivo cardiac function.
AB  - BACKGROUND: Saturated fatty acid-rich high fat (HF) diets trigger abdominal
      adiposity, insulin resistance, type 2 diabetes and cardiac dysfunction. This
      study was aimed at evaluating the effects of nascent obesity on the cardiac
      function of animals fed a high-fat diet and at analyzing the mechanisms by which
      these alterations occurred at the level of coronary reserve. MATERIALS AND
      METHODS: Rats were fed a control (C) or a HF diet containing high proportions of
      saturated fatty acids for 3 months. Thereafter, their cardiac function was
      evaluated in vivo using a pressure probe inserted into the cavity of the left
      ventricle. Their heart was isolated, perfused iso-volumetrically according to the
      Langendorff mode and the coronary reserve was evaluated by determining the
      endothelial-dependent (EDV) and endothelial-independent (EIV) vasodilatations in
      the absence and presence of endothelial nitric oxide synthase and cyclooxygenase
      inhibitors (L-NAME and indomethacin). The fatty acid composition of cardiac
      phospholipids was then evaluated. RESULTS: Although all the HF-fed rats increased
      their abdominal adiposity, some of them did not gain body weight (HF- group)
      compared to the C group whereas other ones had a higher body weight (HF+). All HF
      rats displayed a higher in vivo cardiac activity associated with an increased
      EDV. In the HF- group, the improved EDV was due to an increase in the endothelial
      cell vasodilatation activity whereas in the HF+ group, the enhanced EDV resulted
      from an improved sensitivity of coronary smooth muscle cells to nitric oxide.
      Furthermore, in the HF- group the main pathway implicated in the EDV was the NOS
      pathway while in the HF+ group the COX pathway. CONCLUSIONS: Nascent obesity
      induced improvement of cardiac function may be supported by an enhanced coronary
      reserve occurring via different mechanisms. These mechanisms implicate either the
      endothelial cells activity or the smooth muscle cells sensitivity depending on
      the body adiposity of the animals.

PMID- 24572213
TI  - An unusual case of chronic lateral foot pain following ankle inversion injury:
      osteoid osteoma of the tarsal cuboid bone.
AB  - Osteoid osteomas are common benign tumors normally seen in the femur, tibia, and
      spine. They rarely are seen in the foot. We present an unusual case of osteoid
      osteoma of the cuboid in a 26-year-old man. This was initially thought to be an
      ankle sprain, as its first presentation was after a sporting injury. It was then
      treated as an infection before the true diagnosis--that of osteoid osteoma--was
      obtained.

PMID- 24572211
TI  - Probable hepatic capillariosis and hydatidosis in an adolescent from the late
      Roman period buried in Amiens (France).
AB  - Two calcified objects recovered from a 3rd to 4th-century grave of an adolescent
      in Amiens (Northern France) were identified as probable hydatid cysts. By using
      thin-section petrographic techniques, probable Calodium hepaticum (syn.
      Capillaria hepatica) eggs were identified in the wall of the cysts. Human hepatic
      capillariosis has not been reported from archaeological material so far, but
      could be expected given the poor level of environmental hygiene prevalent in this
      period. Identification of tissue-dwelling parasites such as C. hepaticum in
      archaeological remains is particularly dependent on preservation conditions and
      taphonomic changes and should be interpreted with caution due to morphological
      similarities with Trichuris sp. eggs. 

PMID- 24572214
TI  - Fifth metatarsal fractures.

PMID- 24572215
TI  - Predictive nature of prefrontal theta oscillation on the performance of trace
      conditioned eyeblink responses in guinea pigs.
AB  - Stimulus-evoked theta oscillations are observed in the medial prefrontal cortex
      (mPFC) when executing a variety of learning tasks. Here, we aimed to further
      determine whether spontaneous theta-band (5.0-10.0 Hz) oscillations in the mPFC
      predicted the subsequent behavioral performance in trace eyeblink conditioning
      (TEBC), in which the conditioned stimulus (CS) was separated from the
      unconditioned stimulus (US) by 500 ms trace interval. By recording local field
      potentials (LFP) signals in the guinea pigs performing the TEBC task, we found
      that, a higher mPFC relative theta ratio [theta/(delta+beta)] during the baseline
      (850-ms period prior to the onset of the CS) was predictive of higher magnitude
      and more adaptive timing rather than faster acquisition of trace conditioned
      eyeblink responses (CR). However, the prediction of baseline mPFC theta activity
      was time-limited to the well-learning stage. Additionally, the relative power of
      mPFC theta activity did not correlate with the CR performance if the trace
      interval between the CS and the US was shortened to 100 ms. These results suggest
      that the brain state in which the baseline mPFC theta activity is present or
      absent is detrimental for the subsequent performance of trace CRs especially when
      the asymptotic learning state is achieved.

PMID- 24572216
TI  - Double-V scrotoplasty for repair of congenital penoscrotal webbing: a hidden scar
      technique.
AB  - OBJECTIVE: Penoscrotal webbing (PSW) is a common reason for deferral of neonatal
      circumcision. Reports of successful procedures and outcomes in the literature are
      sparse. We have performed double-V scrotoplasty (DVS), a modification of a V-Y
      technique, in 138 patients with excellent results. PATIENTS AND METHODS: We
      retrospectively reviewed the charts of boys who had undergone DVS for PSW since
      January 2009 by a single surgeon (S.A.A.). The indications, intraoperative
      findings, concomitant procedures, outcomes, and complications were recorded.
      RESULTS: A total of 138 DVSs were performed. Concomitant genital surgeries
      included 81 hidden penis repairs and 10 other (hernia, hypospadias, chordee,
      orchidopexy). The median age at the time of surgery was 9.6 months (6.1 months
      9.8 years). Patients were evaluated about 1 month postoperatively. In seven cases
      (5%), minor skin separation occurred at the penoscrotal junction but all healed
      completely. Superficial skin infection occurred in one patient. None required
      reoperation and cosmetic results were subjectively excellent. CONCLUSIONS: PSW
      has been corrected in 138 patients without significant complications and with
      excellent results. This is the largest known peer-reviewed series evaluating a
      surgical technique for congenital PSW repair. We believe our technique is simple,
      reproducible, and, with no diverging suture lines lateral to the median raphe,
      improves cosmesis.

PMID- 24572217
TI  - Mapping collective behavior in the big-data era.
AB  - The behavioral sciences have flourished by studying how traditional and/or
      rational behavior has been governed throughout most of human history by
      relatively well-informed individual and social learning. In the online age,
      however, social phenomena can occur with unprecedented scale and
      unpredictability, and individuals have access to social connections never before
      possible. Similarly, behavioral scientists now have access to "big data" sets -
      those from Twitter and Facebook, for example - that did not exist a few years
      ago. Studies of human dynamics based on these data sets are novel and exciting
      but, if not placed in context, can foster the misconception that mass-scale
      online behavior is all we need to understand, for example, how humans make
      decisions. To overcome that misconception, we draw on the field of discrete
      choice theory to create a multiscale comparative "map" that, like a principal
      components representation, captures the essence of decision making along two
      axes: (1) an east-west dimension that represents the degree to which an agent
      makes a decision independently versus one that is socially influenced, and (2) a
      north-south dimension that represents the degree to which there is transparency
      in the payoffs and risks associated with the decisions agents make. We divide the
      map into quadrants, each of which features a signature behavioral pattern. When
      taken together, the map and its signatures provide an easily understood empirical
      framework for evaluating how modern collective behavior may be changing in the
      digital age, including whether behavior is becoming more individualistic, as
      people seek out exactly what they want, or more social, as people become more
      inextricably linked, even "herdlike," in their decision making. We believe the
      map will lead to many new testable hypotheses concerning human behavior as well
      as to similar applications throughout the social sciences. 

PMID- 24572218
TI  - "Big data" needs an analysis of decision processes.
AB  - We demonstrate by means of a simulation that the conceptual map presented by
      Bentley et al. is incomplete without taking into account people's decision
      processes. Within the same environment, two decision processes can generate
      strikingly different collective behavior; in two environments that fundamentally
      differ in transparency, a single process gives rise to virtually identical
      behavior. 

PMID- 24572219
TI  - "The map is not the territory".
AB  - Bentley et al.'s claim that their "map ... captures the essence of decision
      making" (target article, Abstract) is deconstructed and shown to originate in a
      serious misunderstanding of the role of principal components and statistical
      graphics in the generation of pattern claims and hypotheses from profile data.
      Three alternative maps are offered, each with its radiation of further
      investigations. 

PMID- 24572220
TI  - Extending the global village: emotional communication in the online age.
AB  - Bentley et al.'s analysis of how human decision-making has changed in the online
      age does not mention emotion. Although the suggested dimensions involving social
      influence and transparency are interesting and suggestive, the engines behind the
      changes wrought by online media are arguably largely emotional, and implications
      of the communication of specific emotions via online media need to be better
      understood. 

PMID- 24572221
TI  - Mapping collective behavior--beware of looping.
AB  - We discuss ambiguities of the two main dimensions of the map proposed by Bentley
      and colleagues that relate to the degree of self-reflection the observed agents
      have upon their behavior. This self-reflection is a variant of the "looping
      effect" which denotes that, in social research, the product of investigation
      influences the object of investigation. We outline how this can be understood as
      a dimension of "height" in the map of Bentley et al. 

PMID- 24572222
TI  - Modesty can be constructive: linking theory and evidence in social science.
AB  - This commentary argues that Bentley et al.'s mapping of shifts in collective
      human behavior provides a novel vision of how social science theory can inform
      large data set analysis. 

PMID- 24572223
TI  - The crowd is self-aware.
AB  - Bentley et al.'s framework assigns phenomena of personal and collective decision
      making to regions of a dual-axis map. Here, we propose that understanding the
      collective dynamics of decision-making requires consideration of factors that
      guide movement across the map. One such factor is self-awareness, which can lead
      a group to seek out new knowledge and re-position itself on the map. 

PMID- 24572224
TI  - Adding network structure onto the map of collective behavior.
AB  - We propose an extension to the map of Bentley et al. by incorporating an aspect
      of underlying network structure that is likely relevant for many modes of
      collective behavior. This dimension, which captures a feature of network
      community structure, is known both from theory and from experiments to be
      relevant for decision-making processes. 

PMID- 24572225
TI  - Missing emotions: the Z-axis of collective behavior.
AB  - Bentley et al. bypass the relevance of emotions in decision-making, resulting in
      a possible over-simplification of behavioral types. We propose integrating
      emotions, both in the north-south axis (in relation to cognition) as well as in
      the west-east axis (in relation to social influence), by suggesting a Z-axis, in
      charge of registering emotional depth and involvement. 

PMID- 24572226
TI  - Capturing the essence of decision making should not be oversimplified.
AB  - Bentley et al. propose a thought-provoking approach to the question of causal
      factors underlying human choice behavior. Their map model is interesting, but too
      simplified to capture the essence of decision making. They disregard, among other
      matters, qualitative differences between various subcategories of social
      influences, and the role of neurobiological factors engaged in interdependent
      individual and social decision-making processes. 

PMID- 24572227
TI  - Conflicting goals and their impact on games where payoffs are more or less
      ambiguous.
AB  - The two-dimensional map by Bentley et al. concerns decision-making and not games.
      The east-west dimension is interpreted as the level at which individuals identify
      with some larger group. We think that this should be linked to the concept of
      social ties. We argue that social ties will lead to different outcomes in the
      "north" compared to the "south." 

PMID- 24572228
TI  - It's distributions all the way down!: second order changes in statistical
      distributions also occur.
AB  - The textual, big-data literature misses Bentley et al.'s message on
      distributions; it largely examines the first-order effects of how a single,
      signature distribution can predict population behaviour, neglecting second-order
      effects involving distributional shifts, either between signature distributions
      or within a given signature distribution. Indeed, Bentley et al. themselves under
      emphasise the potential richness of the latter, within-distribution effects. 

PMID- 24572229
TI  - Keeping conceptual boundaries distinct between decision making and learning is
      necessary to understand social influence.
AB  - Bentley et al. make the deliberate choice to blur the distinction between
      learning and decision making. This obscures the social influence mechanisms that
      operate in the various empirical settings that their map aims to categorize.
      Useful policy prescriptions, however, require an accurate understanding of the
      social influence mechanisms that underlie the dynamics of popularity. 

PMID- 24572230
TI  - Alternative maps of the world of collective behaviors.
AB  - I compare the collective behavior map proposed by Bentley et al. ("BOB" for
      short) with a similar "balance of pressures" (BOP) map proposed by MacCoun
      (2012). The BOB and BOP maps have important points of convergence, but also some
      differences. The comparison suggests that they are analogous to different map
      "projections" for maps of Earth - different ways of simplifying a complex
      reality. 

PMID- 24572231
TI  - Coordination games, anti-coordination games, and imitative learning.
AB  - Bentley et al.'s scheme generates distributions characteristic of situations of
      high and low social influence on decisions and of high and low salience
      ("transparency") of rewards. Another element of decisions that may influence the
      placement of a decision process in their map is the way in which individual
      decisions interact to determine the payoffs. This commentary discusses the role
      of Nash equilibria in game theory, focusing especially on coordination and anti
      coordination games. 

PMID- 24572232
TI  - Cultural evolution in more than two dimensions: distinguishing social learning
      biases and identifying payoff structures.
AB  - Bentley et al.'s two-dimensional conceptual map is complementary to cultural
      evolution research that has sought to explain population-level cultural dynamics
      in terms of individual-level behavioral processes. Here, I qualify their scheme
      by arguing that different social learning biases should be treated distinctly,
      and that the transparency of decisions is sometimes conflated with the actual
      underlying payoff structure of those decisions. 

PMID- 24572233
TI  - Using big data to predict collective behavior in the real world.
AB  - Recent studies provide convincing evidence that data on online information
      gathering, alongside massive real-world datasets, can give new insights into real
      world collective decision making and can even anticipate future actions. We argue
      that Bentley et al.'s timely account should consider the full breadth, and, above
      all, the predictive power of big data. 

PMID- 24572234
TI  - The missing dimension: the relevance of people's conception of time.
AB  - While a timely conceptual innovation for the digital age, the "map" proposed by
      Bentley et al. would benefit from strengthening through the inclusion of a non
      clock-time perspective. In this way, there could be new hypotheses developed
      which could be applied and tested relevant to more diverse societies, cultures,
      and individuals. 

PMID- 24572235
TI  - Big data in the new media environment.
AB  - Bentley et al. argue for the social scientific contextualization of "big data" by
      proposing a four-quadrant model. We suggest extensions of the east-west (i.e.,
      socially motivated versus independently motivated) decision-making dimension in
      light of findings from social psychology and neuroscience. We outline a method
      that leverages linguistic tools to connect insights across fields that address
      the individuals underlying big-data media streams. 

PMID- 24572236
TI  - Independent decisions are fictional from a psychological perspective.
AB  - Contrasting independent with socially influenced decision making does not capture
      crucial differences in decision making. Independence is fictional, and social
      influences substantially permeate preference construction. A distinction between
      deliberate and intuitive decision making would be more useful, and the problem in
      the big-data era is deciding when it is better to rely on deliberation and when
      to trust one's intuitions. 

PMID- 24572237
TI  - What shapes social decision making?
AB  - Outcome transparency and the weight given to social information both play
      important roles in decision making, but we argue that an overarching influence is
      the degree to which individuals can and do gather information. Evolution,
      experience, and development may shape individual specializations in social
      decision making that carry over across contexts, and these individual differences
      may influence collective behavior and cultural evolution. 

PMID- 24572238
TI  - Bigger data for big data: from Twitter to brain-computer interfaces.
AB  - We are sympathetic with Bentley et al.'s attempt to encompass the wisdom of
      crowds in a generative model, but posit that a successful attempt at using big
      data will include more sensitive measurements, more varied sources of
      information, and will also build from the indirect information available through
      technology, from ancillary technical features to data from brain-computer
      interfaces. 

PMID- 24572239
TI  - Economics is all over the map.
AB  - Bentley et al. say that economics is the science of their map's northwest
      quadrant, where choice is individual and transparent. This accepts the picture of
      the discipline common among behavioral economists who aim to drag economics
      southward but not eastward. In fact, leading economics journals regularly publish
      models located in all four quadrants, and the prominence of work from the eastern
      zone is increasing. 

PMID- 24572240
TI  - Understanding social networks requires more than two dimensions.
AB  - The proposed framework is insufficient to categorize and understand current
      evidence on decision making. There are some ambiguities in the questions asked
      that require additional distinctions between correctness and accuracy, decision
      making and learning, accuracy and confidence, and social influence and
      empowerment. Social learning techniques are not all the same: Behavior copying is
      quite different from theory passing. Sigmoidal acquisition curves are not unique
      to social learning and are often mistaken for other accelerating curves. 

PMID- 24572241
TI  - The global shift: shadows of identifiability.
AB  - The presence of overwhelming amounts of information in our big-data era society
      is growing. Globalisation is increasingly giving these solicitations (regarding
      information) a more social aspect causing behavioural changes. While restricting
      my focus on this aspect of the Bentley et al article, I address related medical
      questions and pin-point the conceptual interest of the roadmap given therein. 

PMID- 24572242
TI  - A map of where? Problems with the "transparency" dimension.
AB  - Transparency is a fundamental concept in the target article by Bentley et al. But
      the text gives cryptic, inconclusive and sometimes conflicting suggestions as to
      what transparency consists of. Consequently, it is insufficiently clear what the
      north-south axis of the map of collective behaviour actually represents, or how
      to order behaviours by transparency. 

PMID- 24572243
TI  - Using big data to map the network organization of the brain.
AB  - The past few years have shown a major rise in network analysis of "big data" sets
      in the social sciences, revealing non-obvious patterns of organization and
      dynamic principles. We speculate that the dependency dimension - individuality
      versus sociality - might offer important insights into the dynamics of neurons
      and neuronal ensembles. Connectomic neural analyses, informed by social network
      theory, may be helpful in understanding underlying fundamental principles of
      brain organization. 

PMID- 24572244
TI  - Mapping collective emotions to make sense of collective behavior.
AB  - While Bentley et al.'s model is very appealing, in this commentary we argue that
      researchers interested in big data and collective behavior, including the way
      humans make decisions, must account for the emotional factor. We investigate how
      daily choice of activities is influenced by emotions. Results indicate that mood
      significantly predicts people's decisions about what to do next, stressing the
      importance of emotional state on decision-making. 

PMID- 24572245
TI  - Conformity under uncertainty: reliance on gender stereotypes in online hiring
      decisions.
AB  - We apply Bentley et al.'s theoretical framework to better understand gender
      discrimination in online labor markets. Although such settings are designed to
      encourage employer behavior in the northwest corner of Homo economicus, actual
      online hiring decisions tend to drift southeast into a "confirmation bias plus
      weak feedback loops" pattern of discrimination based on inaccurate social
      stereotypes. 

PMID- 24572246
TI  - Interaction between social influence and payoff transparency.
AB  - Social influence and payoff transparency interact with each other to influence
      decision making. Social influence masks payoff transparency, and lacking
      transparency drives people to seek social influence. Moreover, our survey
      supports our claim by showing that social influence and payoff transparency
      correlate with each other (r(53) = -.71). Bentley et al.'s model can be revised
      to accommodate the covariance. 

PMID- 24572248
TI  - Hypercalcemia in a male-to-female transgender patient after body contouring
      injections: a case report.
AB  - INTRODUCTION: Body contouring injections by non-licensed providers are frequently
      sought out by a subset of the male-to-female transgender community. Although
      short-term side effects such as pulmonary embolism and injection site infection
      are well known, long-term consequences of such practices are less well studied.
      CASE PRESENTATION: Here we describe the case of a 40-year-old African American
      male-to-female transgender patient who presented to our institution with
      hypercalcemia and acute renal failure secondary to body contouring injections
      with industrial strength silicone by non-licensed providers, a decade prior to
      her visit. Work-up revealed an extensive granulomatous inflammatory process in
      the injection area resulting in electrolyte abnormalities and kidney injury. The
      patient's lab results and symptoms responded well to long-term corticosteroid
      treatment and correlated with treatment adherence. CONCLUSION: Affected patients
      can sometimes present with unusual clinical symptoms many years after silicone
      injections. In a constantly growing transgender community that often utilizes non
      licensed providers for silicone injections, the medical community will likely
      face an increasing number of patients with long-term side effects of such
      practices. Therefore, it is imperative for physicians to recognize such cases
      promptly and initiate potentially life-saving treatment.

PMID- 24572249
TI  - Serum cholesterol concentration and prevalence, awareness, treatment, and control
      of high low-density lipoprotein cholesterol in the Korea National Health and
      Nutrition Examination Surveys 2008-2010: Beyond the Tip of the Iceberg.
AB  - BACKGROUND: The mortality rate from cardiovascular disease (CVD) among young
      adults has declined less than that in the older population, raising concerns
      about the increasing prevalence of obesity-related conditions including
      hypercholesterolemia in the younger population. We investigated the age
      standardized mean levels of serum cholesterols and the prevalence, awareness,
      treatment and control rates of hyper-low-density lipoprotein (LDL)
      cholesterolemia based on age. METHODS AND RESULTS: Nationally representative
      samples of 19 489 subjects aged >=20 years were analyzed from the Korea National
      Health and Nutrition Examination Surveys 2008-2010. Hyper-LDL-cholesterolemia was
      individually evaluated by the 2004 National Cholesterol Education Program Adult
      Treatment Panel III guidelines. Age-standardized mean levels of total
      cholesterol, high-density lipoprotein-cholesterol, LDL-cholesterol, and
      triglycerides were 186.8, 48.0, 112.9, and 136.0 mg/dL, respectively. Age
      standardized prevalence of hyper-LDL-cholesterolemia was 23.2% (men, 25.5%;
      women, 21.8%). Among subjects with hyper-LDL-cholesterolemia, awareness and
      treatment rates were significantly lower in younger adults (<50 years) compared
      to older adults >=50 years (awareness, 8.0% versus 21.5%; treatment, 5.1% versus
      18.5%, all Ps<0.001), indicating significant discrepancies in awareness and
      treatment rates of hypercholesterolemia between younger and older adults. Among
      subjects aware of their hyper-LDL-cholesterolemia, younger adults were more
      likely to have controlled LDL-cholesterol than the elderly (82.1% versus 67.5%,
      P<0.001). CONCLUSIONS: Compared to the elderly, significant proportions of young
      and middle-aged adults are unaware of their hypercholesterolemia and are not
      treated with proper lipid-lowering medications. Early screening, education, and
      proper management should be stressed in national public healthcare policies to
      reduce the increasing burden of CVD in the younger population with undiagnosed
      hypercholesterolemia.

PMID- 24572250
TI  - Enigmatic ectopic fat: prevalence of nonalcoholic fatty pancreas disease and its
      associated factors in a Chinese population.
AB  - BACKGROUND: Fatty infiltration of the pancreas is an enigmatic manifestation of
      ectopic fat deposition in obesity. Studies have shown that pancreatic lipid
      accumulation interferes with insulin secretion in humans. However, the prevalence
      of fatty pancreas and its associated factors in the general population remain
      unclear. The aim of this study was to investigate the prevalence of fatty
      pancreas and its association with diabetes, nonalcoholic fatty liver disease
      (NAFLD), and cardiometabolic risk factors in a Chinese population. METHODS AND
      RESULTS: This was a cross-sectional study. A total of 8097 subjects with or
      without fatty pancreas (n=1297 and 6800, respectively) were recruited. Each
      subject was assessed by using abdominal sonography to diagnose NAFLD and fatty
      pancreas. Clinical and metabolic parameters were compared between groups, and
      their associations with fatty pancreas were examined. The prevalence of fatty
      pancreas was 16%. The fatty pancreas group had a significantly greater proportion
      of subjects with diabetes (12.6% versus 5.2%) and NAFLD (67.2% versus 35.1%) than
      did the non-fatty pancreas group (P<0.001). In the logistic regression analysis,
      age (P<0.001), general or central obesity (P<0.001), diabetes (P<0.001), and
      NAFLD (P<0.001) were independently associated with fatty pancreas after
      adjustment for sex, lipid profile, alanine transaminase/aspartate transaminase
      ratio, hypertension, smoking, alcohol drinking, and exercise. CONCLUSIONS: The
      prevalence of fatty pancreas is high in the general population. Both diabetes and
      NAFLD are important associated factors of fatty pancreas, independent of age,
      sex, adiposity, and other cardiometabolic risk factors.

PMID- 24572251
TI  - Thrombolysis delivery by a regional telestroke network--experience from the U.K.
      National Health Service.
AB  - BACKGROUND: The majority of established telestroke services are based on "hub-and
      spoke" models for providing acute clinical assessment and thrombolysis. We report
      results from the first year of the successful implementation of a locally based
      telemedicine network, without the need of 1 or more hub hospitals, across a
      largely rural landscape. METHODS AND RESULTS: Following a successful pilot phase
      that demonstrated safety and feasibility, the East of England telestroke project
      was rolled out across 7 regional hospitals, covering an area of 7500 square miles
      and a population of 5.6 million to enable out-of-hours access to thrombolysis.
      Between November 2010 and November 2011, 142 telemedicine consultations were
      recorded out-of-hours. Seventy-four (52.11%) cases received thrombolysis. Median
      (IQR) onset-to-needle and door-to-needle times were 169 (141.5 to 201.5) minutes
      and 94 (72 to 113.5) minutes, respectively. Symptomatic hemorrhage rate was 7.3%
      and stroke mimic rate was 10.6%. CONCLUSIONS: We demonstrate the safety and
      effectiveness of a horizontal networking approach for stroke telemedicine, which
      may be applicable to areas where traditional "hub-and-spoke" models may not be
      geographically feasible.

PMID- 24572252
TI  - Mechanism of the susceptibility of remodeled pulmonary vessels to drug-induced
      cell killing.
AB  - BACKGROUND: Pulmonary arterial hypertension remains a devastating disease without
      a cure. The major complication of this disease is the abnormal growth of vascular
      cells, resulting in pulmonary vascular remodeling. Thus, agents, which affect the
      remodeled vessels by killing unwanted cells, should improve treatment strategies.
      The present study reports that antitumor drugs selectively kill vascular cells in
      remodeled pulmonary vessels in rat models of pulmonary hypertension. METHODS AND
      RESULTS: After developing pulmonary vascular remodeling in chronic hypoxia or
      chronic hypoxia/SU-5416 models, rats were injected with antitumor drugs including
      proteasome inhibitors (bortezomib and MG-132) and daunorubicin. Within 1 to 3
      days, these agents reduced the media and intima thickness of remodeled pulmonary
      vascular walls, but not the thickness of normal pulmonary vessels. These drugs
      also promoted apoptotic and autophagic death of vascular cells in the remodeled
      vessels, but not in normal vessels. We provide evidence that the upregulation of
      annexin A1, leading to GATA4-dependent downregulation of Bcl-xL, is a mechanism
      for specific apoptotic killing, and for the role of parkin in defining
      specificity of autophagic killing of remodeled vascular cells. The reversal of
      pulmonary vascular remodeling increased the capacity of vasodilators to reduce
      pulmonary arterial pressure. CONCLUSIONS: These results suggest that antitumor
      drugs can specifically kill cells in remodeled pulmonary vascular walls and may
      be useful for improving the efficacy of current therapeutic strategies to treat
      pulmonary arterial hypertension.

PMID- 24572253
TI  - Consumption of less than 10% of total energy from added sugars is associated with
      increasing HDL in females during adolescence: a longitudinal analysis.
AB  - BACKGROUND: Atherosclerotic changes associated with dyslipidemia and increased
      cardiovascular disease risk are believed to begin in childhood. While previous
      studies have linked added sugars consumption to low high-density lipoprotein
      (HDL), little is known about the long-term impact of this consumption. This study
      aims to assess the association between added sugars intake and HDL cholesterol
      levels during adolescence, and whether this association is modified by obesity.
      METHODS AND RESULTS: We used data from the National Heart Lung and Blood
      Institute's Growth and Health Study, a 10-year cohort study of non-Hispanic
      Caucasian and African-American girls (N=2379) aged 9 and 10 years at baseline
      recruited from 3 sites in 1987-1988 with biennial plasma lipid measurement and
      annual assessment of diet using a 3-day food record. Added sugars consumption was
      dichotomized into low (0% to <10% of total energy) and high (>=10% of total
      energy). In a mixed model controlling for obesity, race, physical activity,
      smoking, maturation stage, age, and nutritional factors, low compared with high
      added sugar consumption was associated with a 0.26 mg/dL greater annual increase
      in HDL levels (95% CI 0.48 to 0.04; P=0.02). Over the 10-year study period, the
      model predicted a mean increase of 2.2 mg/dL (95% CI 0.09 to 4.32; P=0.04) among
      low consumers, and a 0.4 mg/dL decrease (95% CI -1.32 to 0.52; P=0.4) among high
      consumers. Weight category did not modify this association (P=0.45). CONCLUSION:
      Low added sugars consumption is associated with increasing HDL cholesterol levels
      throughout adolescence.

PMID- 24572254
TI  - Dysferlin mediates the cytoprotective effects of TRAF2 following myocardial
      ischemia reperfusion injury.
AB  - BACKGROUND: We have demonstrated that tumor necrosis factor (TNF) receptor
      associated factor 2 (TRAF2), a scaffolding protein common to TNF receptors 1 and
      2, confers cytoprotection in the heart. However, the mechanisms for the
      cytoprotective effects of TRAF2 are not known. METHODS/RESULTS: Mice with cardiac
      restricted overexpression of low levels of TRAF2 (MHC-TRAF2LC) and a dominant
      negative TRAF2 (MHC-TRAF2DN) were subjected to ischemia (30-minute) reperfusion
      (60-minute) injury (I/R), using a Langendorff apparatus. MHC-TRAF2LC mice were
      protected against I/R injury as shown by a significant ~27% greater left
      ventricular (LV) developed pressure after I/R, whereas mice with impaired TRAF2
      signaling had a significantly ~38% lower LV developed pressure, a ~41% greater
      creatine kinase (CK) release, and ~52% greater Evans blue dye uptake after I/R,
      compared to LM. Transcriptional profiling of MHC-TRAF2LC and MHC-TRAF2DN mice
      identified a calcium-triggered exocytotic membrane repair protein, dysferlin, as
      a potential cytoprotective gene responsible for the cytoprotective effects of
      TRAF2. Mice lacking dysferlin had a significant ~39% lower LV developed pressure,
      a ~20% greater CK release, and ~29% greater Evans blue dye uptake after I/R,
      compared to wild-type mice, thus phenocopying the response to tissue injury in
      the MHC-TRAF2DN mice. Moreover, breeding MHC-TRAF2LC onto a dysferlin-null
      background significantly attenuated the cytoprotective effects of TRAF2 after I/R
      injury. CONCLUSION: The study shows that dysferlin, a calcium-triggered
      exocytotic membrane repair protein, is required for the cytoprotective effects of
      TRAF2-mediated signaling after I/R injury.

PMID- 24572255
TI  - Relative importance of step count, intensity, and duration on physical activity's
      impact on vascular structure and function in previously sedentary older adults.
AB  - BACKGROUND: Age-related endothelial dysfunction and vascular stiffening are
      associated with increased cardiovascular (CV) risk. Many groups have encouraged
      goals of >=10 000 steps/day or >=30 min/day of moderate intensity physical
      activity (MPA) to reduce age-related CV risk. The impact of MPA on the
      vasculature of older adults remains unclear. METHODS AND RESULTS: We randomized
      114 sedentary older adults ages >=50 to 12 weeks of either no intervention (group
      1), a pedometer-only intervention (group 2), or a pedometer with an interactive
      website employing strategies to increase the adoption of habitual physical
      activity (PA, group 3). Endothelial function by brachial flow-mediated dilation
      (FMD%), vascular stiffness by tonometry, step-count by pedometer, and PA
      intensity/distribution by accelerometer were measured. Step-count increased in
      groups 2 (5136+/-1554 to 9596+/-3907, P<0.001) and 3 (5474+/-1512 to 8167+/-3111,
      P<0.001) but not in group 1 (4931+/-1667 to 5410+/-2410). Both groups 2 and 3
      increased MPA >=30 min/day. Only group 3 increased MPA in continuous bouts of
      >=10 minutes (P<0.001) and improved FMD% (P=0.001). Neither achievement of >=10
      000 steps/day nor >=30 min/day of MPA resulted in improved FMD%. However,
      achieving >=20 min/day in MPA bouts resulted in improved FMD%. No changes in
      vascular stiffness were observed. CONCLUSIONS: MPA reverses age-related
      endothelial dysfunction, but may require MPA to be performed in bouts of >=10
      minutes duration for >=20 min/day to be effective. Commonly encouraged PA goals
      do not guarantee improved endothelial function and may not be as effective in
      reducing CV risk. CLINICAL TRIAL REGISTRATION URL: Clinicaltrials.gov. UNIQUE
      IDENTIFIER: NCT-01212978.

PMID- 24572256
TI  - Monoamine oxidase is a major determinant of redox balance in human atrial
      myocardium and is associated with postoperative atrial fibrillation.
AB  - BACKGROUND: Onset of postoperative atrial fibrillation (POAF) is a common and
      costly complication of heart surgery despite major improvements in surgical
      technique and quality of patient care. The etiology of POAF, and the ability of
      clinicians to identify and therapeutically target high-risk patients, remains
      elusive. METHODS AND RESULTS: Myocardial tissue dissected from right atrial
      appendage (RAA) was obtained from 244 patients undergoing cardiac surgery.
      Reactive oxygen species (ROS) generation from multiple sources was assessed in
      this tissue, along with total glutathione (GSHt) and its related enzymes GSH
      peroxidase (GPx) and GSH-reductase (GR). Monoamine oxidase (MAO) and NADPH
      oxidase were observed to generate ROS at rates 10-fold greater than intact,
      coupled mitochondria. POAF risk was significantly associated with MAO activity
      (Quartile 1 [Q1]: adjusted relative risk [ARR]=1.0; Q2: ARR=1.8, 95% confidence
      interval [CI]=0.84 to 4.0; Q3: ARR=2.1, 95% CI=0.99 to 4.3; Q4: ARR=3.8, 95%
      CI=1.9 to 7.5; adjusted Ptrend=0.009). In contrast, myocardial GSHt was inversely
      associated with POAF (Quartile 1 [Q1]: adjusted relative risk [ARR]=1.0; Q2:
      ARR=0.93, 95% confidence interval [CI]=0.60 to 1.4; Q3: ARR=0.62, 95% CI=0.36 to
      1.1; Q4: ARR=0.56, 95% CI=0.34 to 0.93; adjusted Ptrend=0.014). GPx also was
      significantly associated with POAF; however, a linear trend for risk was not
      observed across increasing levels of the enzyme. GR was not associated with POAF
      risk. CONCLUSIONS: Our results show that MAO is an important determinant of redox
      balance in human atrial myocardium, and that this enzyme, in addition to GSHt and
      GPx, is associated with an increased risk for POAF. Further investigation is
      needed to validate MAO as a predictive biomarker for POAF, and to explore this
      enzyme's potential role in arrhythmogenesis.

PMID- 24572260
TI  - From the editor.

PMID- 24572261
TI  - Dancing medicine.

PMID- 24572257
TI  - Autoimmune basis for postural tachycardia syndrome.
AB  - BACKGROUND: Patients with postural tachycardia syndrome (POTS) have exaggerated
      orthostatic tachycardia often following a viral illness, suggesting autoimmunity
      may play a pathophysiological role in POTS. We tested the hypothesis that they
      harbor functional autoantibodies to adrenergic receptors (AR). METHODS AND
      RESULTS: Fourteen POTS patients (7 each from 2 institutions) and 10 healthy
      subjects were examined for alpha1AR autoantibody-mediated contractility using a
      perfused rat cremaster arteriole assay. A receptor-transfected cell-based assay
      was used to detect the presence of beta1AR and beta2AR autoantibodies. Data were
      normalized and expressed as a percentage of baseline. The sera of all 14 POTS
      patients demonstrated significant arteriolar contractile activity (69+/-3%
      compared to 91+/-1% of baseline for healthy controls, P<0.001) when coexisting
      beta2AR dilative activity was blocked; and this was suppressed by alpha1AR
      blockade with prazosin. POTS sera acted as a partial alpha1AR antagonist
      significantly shifting phenylephrine contractility curves to the right. All POTS
      sera increased beta1AR activation (130+/-3% of baseline, P<0.01) and a subset had
      increased beta2AR activity versus healthy subjects. POTS sera shifted
      isoproterenol cAMP response curves to the left, consistent with enhanced beta1AR
      and beta2AR agonist activity. Autoantibody-positive POTS sera demonstrated
      specific binding to beta1AR, beta2AR, and alpha1AR in transfected cells.
      CONCLUSIONS: POTS patients have elevated alpha1AR autoantibodies exerting a
      partial peripheral antagonist effect resulting in a compensatory sympathoneural
      activation of alpha1AR for vasoconstriction and concurrent betaAR-mediated
      tachycardia. Coexisting beta1AR and beta2AR agonistic autoantibodies facilitate
      this tachycardia. These findings may explain the increased standing plasma
      norepinephrine and excessive tachycardia observed in many POTS patients.

PMID- 24572258
TI  - Endothelial KLF4: crippling vascular injury?

PMID- 24572259
TI  - Circulating microRNAs: understanding the limits for quantitative measurement by
      real-time PCR.

PMID- 24572262
TI  - Introduction.

PMID- 24572263
TI  - An easy way to quantity plantarflexion in the ankle.
AB  - A simple, reliable, replicable technique, which takes but moments to perform, is
      available to quantify ankle plantarflexion. The ability to accurately measure
      plantarflexion enables a normal value of plantarflexion to be placed upon the
      professional dancer's ankle. Values are set forth for both male and female
      dancers, based on n = 811. Common and less common complaints in the dancer's foot
      and ankle are described in relation to deviations from this norm, as an aid in
      diagnosis, treatment and prognosis. 

PMID- 24572264
TI  - Differential diagnosis and treatment of posterior ankle pain in dancers and
      equinus athletes.
AB  - Posterior ankle pain in dancers and equinus athletes is often caused by the
      extreme plantarflexion requirements of their activity. Differentiation between
      true posterior ankle pain and Achilles tendon pain is discussed. Signs and
      symptoms of posterior ankle pain are specific to the flexor hallicus tendon on
      the medial side or impingement when on the lateral side. Surgical exploration as
      well as conservative treatment is discussed. 

PMID- 24572265
TI  - Leg length discrepancy in the professional dancer.
AB  - Minor leg length discrepancies may not pose much of a problem in the general
      population, but in the dance population they should not be overlooked as a
      predisposing factor in overuse syndromes commonly found among dancers. The
      popular treatment of prescribing lift therapy is often inappropriate in this
      population as the patient may not wear a shoe during dance or may refuse a lift
      in their shoe as it interferes with the 'feel' of the floor. The key to
      successful treatment in the dancer is a thorough biomechanical evaluation and
      analysis of compensatory mechanisms. In this article, clinical evaluation of leg
      length discrepancy, common compensatory mechanisms, and clinical management in
      the dancer are discussed. An illustrative case study is presented to highlight
      some of the points made. 

PMID- 24572266
TI  - Functional movement impairment in dancers: An assessment and treatment approach
      utilizing the Biomechanical Asymmetry Corrector (BAC) to restore normal mechanics
      of the spine and pelvis.
AB  - Musculoskeletal injuries to the spine and pelvis are common in dancers. These
      injuries are associated with mechanical dysfunctions that impair spinal
      adaptation to the movement demands of the art form. This article introduces the
      biomechanical asymmetry corrector (BAC), a dynamic assessment and treatment tool,
      designed to restore normal spinal mechanics and functional movement patterns in
      dancers. A discussion of lumbo-pelvic mechanics and dance injury provides a
      theoretical context for describing exercises on the BAC. 

PMID- 24572267
TI  - Management adaptations for sacroiliac joint dysfunction in classical dancers.
AB  - Sacroiliac dysfunction occurs frequently in professional classical dancers and
      appears to be linked to the movement demands of the artform and the natural, or
      acquired, ligamentous laxity of its participants. Successful intervention focuses
      on removal of soft tissue and articular restrictions accompanied by the
      appropriate home program. Many treatment adaptations are possible and/or
      necessary when managing the thin, well defined, hypermobile classical dancer. 

PMID- 24572268
TI  - Piriformis involvement in dancers with low back pain - a conservative approach.
AB  - Low back pain is a rather common problem for the dancer, it can account for as
      much as 25% of all dance injuries. Within dance, injury to the piriformis muscle
      can be either due to a single traumatic incident or more commonly from overuse
      factors involved from repetitive micro trauma. The piriformis is of clinical
      importance in classical dance as regards to both low back and leg pain because of
      its close relationship anatomically to the sciatic nerve and biomechanically
      because it is the primary muscle responsible for external rotation of the leg,
      the turnout in dance. Symptoms arising from an involvement of the piriformis
      muscle syndrome are often muddled and often mimic other causes of mechanical low
      back pain. The dancer can either be affected acutely or chronically. It can
      present itself as either low back pain, buttock pain or leg pain, or any
      combination of these. Specific considerations may contribute to this syndrome (a)
      myofascial pain referred from trigger points in the piriformis muscle; (b) nerve
      and vascular entrapment by the piriformis muscle at the greater sciatic foramen;
      and (c) dysfunction of the SI joint. Diagnosis is based on evaluating both the
      static and kinetic functions of the low back and pelvis as well as the
      biomechanics specific to dance. The therapeutic aim of conservative treatment of
      the piriformis syndrome in dancers is aimed at relieving pain, reducing the
      hypertonicity of the piriformis muscle, restoring the biomechanics of the SI
      joint and lumbar spine, and having the dancer return to dance with little or no
      down time. A comprehensive protocol for the conservative treatment of the
      piriformis syndrome is outlined and presented. 

PMID- 24572269
TI  - On pain, illness and disability.
AB  - The biomedical perspective on management of pain, illness, and disability is
      analyzed and discussed. Pain and pain behavior are delineated. The distinction
      between acute and chronic pain, and the potential impact of social and
      environmental factors on pain behavior are reviewed. Distinctions between pain
      and suffering and between specific and non-specific pain are drawn and
      implications for the diagnostic process are considered. The importance of viewing
      clinical pain in biopsychosocial terms is emphasized and implications of that
      conceptual shift are reviewed. Attending to the social/environmental context in
      which patients function leads to an analysis of the social contract between
      individual and society. Implications of the concept of 'effort-related' on
      clinician as well as patient is considered. Clinician potential for stifling
      patient effort is reviewed. Finally implications of a biopsychosocial perspective
      on facilitation of return to work is considered. 

PMID- 24572271
TI  - Adsorption characteristics of selected hydrophilic and hydrophobic
      micropollutants in water using activated carbon.
AB  - In this study, we investigated adsorption characteristics of nine selected
      micropollutants (six pharmaceuticals, two pesticides, and one endocrine
      disruptor) in water using an activated carbon. The effects of carbon dosage,
      contact time, pH, DOM (dissolved organic matter), and temperature on the
      adsorption removal of micropollutants were examined. Increasing carbon dosage and
      contact time enhanced the removal of micropollutants. Sorption coefficients of
      hydrophilic compounds (caffeine, acetaminophen, sulfamethoxazole, and
      sulfamethazine) fit a linear isotherm and hydrophobic compounds (naproxen,
      diclofenac, 2, 4-D, triclocarban, and atrazine) fit a Freundlich isotherm. The
      removal of hydrophobic pollutants and caffeine were independent of pH changes,
      but acetaminophen, sulfamethazine, and sulfamethoxazole were adsorbed by mainly
      electrostatic interaction with activated carbon and so were affected by pH. The
      decrease in adsorption removal in surface water samples was observed and this
      decrease was more significant for hydrophobic than hydrophilic compounds. The
      decline in the adsorption capacity in surface water samples is caused by the
      competitive inhibition of DOM with micropollutants onto activated carbon. Low
      temperature (5 degrees C) also decreased the adsorption removal of
      micropollutants, and affected hydrophobic compounds more than hydrophilic
      compounds. The results obtained in this study can be applied to optimize the
      adsorption capacities of micropollutants using activated carbon in water
      treatment process. 

PMID- 24572272
TI  - New mechanistically based model for predicting reduction of biosolids waste by
      ozonation of return activated sludge.
AB  - Two pilot-scale activated sludge reactors were operated for 98 days to provide
      the necessary data to develop and validate a new mathematical model predicting
      the reduction of biosolids production by ozonation of the return activated sludge
      (RAS). Three ozone doses were tested during the study. In addition to the pilot
      scale study, laboratory-scale experiments were conducted with mixed liquor
      suspended solids and with pure cultures to parameterize the biomass inactivation
      process during exposure to ozone. The experiments revealed that biomass
      inactivation occurred even at the lowest doses, but that it was not associated
      with extensive COD solubilization. For validation, the model was used to simulate
      the temporal dynamics of the pilot-scale operational data. Increasing the
      description accuracy of the inactivation process improved the precision of the
      model in predicting the operational data. 

PMID- 24572273
TI  - Modification of a Ca-montmorillonite with ionic liquids and its application for
      chromate removal.
AB  - Ionic liquids (ILs), due to their low vapor pressure, have been explored as green
      solvents for organic synthesis. In this study, the uptake of ILs on a high charge
      Ca-montmorillonite (MMT) and the use of the IL-modified MMT for the removal of
      anionic contaminants from water were systematically studied. Uptake of ILs by MMT
      was exclusively resulted from a cation exchange mechanism when the initial IL
      concentrations were less than the critical micelle concentration (CMC) and the
      sorbed ILs formed a monolayer conformation on the surface of MMT. When the
      initial IL concentrations were greater than the CMC, both cation exchange and
      hydrophobic interactions were responsible for the IL uptake. The IL molecules
      formed admicelles and the surface charge was reversed to positive balanced by
      counterion Cl(-) when the IL loading was higher than the cation exchange capacity
      of the mineral. The modified MMT could remove chromate from water
      instantaneously, with an adsorption capacity of 190 mmol/kg and a 99.5% removal
      efficiency at an initial chromate concentration of 2.6 mmol/L. These features
      could further expand the application of ILs and enable IL-modified MMT to be used
      as inexpensive sorbents for the removal of chromate and other oxyanions from
      water.

PMID- 24572274
TI  - Vacant hospitals and under-employed nurses: a qualitative study of the nursing
      workforce management situation in Nepal.
AB  - It is vital for all healthcare systems to have a sufficient number of suitably
      trained health professionals including nurses at all levels of health services to
      deliver effective healthcare. An ethnographic, qualitative method was chosen for
      this study, which included open-ended, in-depth interviews with a range of
      stakeholders including student nurses, qualified nurses, nurse managers and
      lecturers, and the human resource co-ordinator in the Ministry of Health and
      Population. Available records and policy documents were also analysed. Study
      findings suggest that there is a severe mal-distribution of the nursing workforce
      in rural and urban healthcare centres in Nepal. Although there is an oversupply
      of newly qualified nurses in hospitals in Kathmandu, the staffing situation
      outside the valley is undesirable. Additionally, the turnover of junior nursing
      staff remains high in major urban hospitals. Most qualified nurses aspire to work
      in developed countries, such as the UK, North America, Australia and New Zealand.
      Between 2000 and 2008, as many as 3000 nurses have left Nepal for jobs in the
      developed west. There is no effective management strategy in place to retain a
      nursing workforce, particularly in rural Nepal. This article concludes by
      proposing some suggestions for a nursing workforce retention policy to address
      this critical issue. 

PMID- 24572275
TI  - PCR-based assay for rapid and specific detection of the new Xanthomonas oryzae
      pv. oryzae K3a race using an AFLP-derived marker.
AB  - We describe the development of a polymerase chain reaction method for the rapid,
      precise, and specific detection of the Xanthomonas oryzae pv. oryzae (Xoo) K3a
      race, the bacterial blight pathogen of rice. The specific primer set was designed
      to amplify a genomic locus derived from an amplified fragment length polymorphism
      specific for the K3a race. The 1,024 bp amplicon was generated from the DNA of 13
      isolates of Xoo K3a races out of 119 isolates of other races, pathovars, and
      Xanthomonas species. The assay does not require isolated bacterial cells or DNA
      extraction. Moreover, the pathogen was quickly detected in rice leaf 2 days after
      inoculation with bacteria and at a distance of 8 cm from the rice leaf 5 days
      later. The results suggest that this PCR-based assay will be a useful and
      powerful tool for the detection and identification of the Xoo K3a race in rice
      plants as well as for early diagnosis of infection in paddy fields. 

PMID- 24572276
TI  - Identification of novel non-metal haloperoxidases from the marine metagenome.
AB  - Haloperoxidase (HPO, E.C.1.11.1.7) is a metal-containing enzyme oxidizing
      halonium species, which can be used in the synthesis of halogenated organic
      compounds, for instance in the production of antimicrobial agents, cosmetics,
      etc., in the presence of halides and H2O2. To isolate and evaluate a novel non
      metal HPO using a culture-independent method, a cassette PCR library was
      constructed from marine seawater in Japan. We first isolated a novel HPO gene
      from Pseudomonas putida ATCC11172 by PCR for constructing the chimeric HPO
      library (HPO11172). HPO11172 showed each single open-reading frame of 828 base
      pairs coding for 276 amino acids, respectively, and showed 87% similarity with P.
      putida IF-3 sequences. Approximately 600 transformants screened for chimeric
      genes between P. putida ATCC11173 and HPO central fragments were able to identify
      113 active clones. Among them, we finally isolated 20 novel HPO genes. Sequence
      analyses of the obtained 20 clones showed higher homology genes with P. putida or
      Sinorhizobium or Streptomyces strains. Although the HPO A9 clone showed the
      lowest homology with HPO11172, clones in group B, including CS19, showed a
      relatively higher homology of 80%, with 70% identy. E. coli cells expressing
      these HPO chimeric genes were able to successfully bioconvert chlorodimedone with
      KBr or KCl as substrate. 

PMID- 24572277
TI  - Expression of the pro-domain-deleted active form of caspase-6 in Escherichia
      coli.
AB  - Caspases are a family of cysteine proteases that play an important role in the
      apoptotic pathway. Caspase-6 is an apoptosis effector that cleaves a variety of
      cellular substrates. The active form of the enzyme is required for use in
      research. However, it has been difficult to obtain sufficient quantities of
      active caspase-6 from Escherichia coli. In the present study, we constructed a
      caspase-6 with a 23-amino-acid deletion in the pro-domain. This engineered enzyme
      was expressed as a soluble protein in E. coli and was purified using affinity
      resin. In vitro enzyme assay and cleavage analysis revealed that the engineered
      active caspase-6 protein had characteristics similar to those of wild-type
      caspase-6. This novel method can be a valuable tool for obtaining active caspase
      6 that can be used for screening caspase-6-specific substrates, which in turn can
      be used to elucidate the function of caspase-6 in apoptosis. 

PMID- 24572278
TI  - Two-stage fermentation for 2-Ketogluconic acid production by Klebsiella
      pneumoniae.
AB  - 2-Ketogluconic acid production by Klebsiella pneumoniae is a pH-dependent
      process, strictly proceeding under acidic conditions. Unfortunately, cell growth
      is inhibited by acidic conditions, resulting in low productivity of 2
      ketogluconic acid. To overcome this deficiency, a two-stage fermentation strategy
      was exploited in the current study. During the first stage, the culture was
      maintained at neutral pH, favoring cell growth. During the second stage, the
      culture pH was switched to acidic conditions favoring 2-ketogluconic acid
      accumulation. Culture parameters, including switching time, dissolved oxygen
      levels, pH, and temperature were optimized for the fed-batch fermentation.
      Characteristics of glucose dehydrogenase and gluconate dehydrogenase were
      revealed in vitro, and the optimal pHs of the two enzymes coincided with the
      optimum culture pH. Under optimum conditions, a total of 186 g/l 2- ketogluconic
      acid was produced at 26 h, and the conversion ratio was 0.98 mol/mol. This
      fermentation strategy has successfully overcome the mismatch between optimum
      parameters required for cell growth and 2-ketogluconic acid accumulation, and
      this result has the highest productivity and conversion ratio of 2-ketogluconic
      and produced by microorganism. 

PMID- 24572279
TI  - Lipid production by a CO2-tolerant green microalga, Chlorella sp. MRA-1.
AB  - Since CO2 concentrations in industrial flue gases are usually 10%-20%, one of the
      prerequisites for efficient CO2 removal by algae is the level of tolerance of
      microalgal species to exposure to high concentrations of CO2. A newly isolated
      microalgal strain, Chlorella sp. MRA-1, could retain growth with high
      concentrations of CO2 up to 15%. The highest lipid productivity for Chlorella sp.
      MRA-1 was 0.118 g/l/day with a 5% CO2 concentration. Octadecenoic acid and
      hexadecanoic acid, the main components of biodiesel, accounted for 70% of the
      total fatty acids. A lipid content of 52% of dry cell weight was achieved with
      limited amounts of nitrogen. Chlorella sp. MRA-1 seems to be an ideal candidate
      for biodiesel production when cultured with high concentrations of CO2. 

PMID- 24572280
TI  - Identification of novel binding partners for caspase-6 using a proteomic
      approach.
AB  - Apoptosis is the process of programmed cell death executed by specific proteases,
      the caspases, which mediate the cleavage of various vital proteins. Elucidating
      the consequences of this endoproteolytic cleavage is crucial to understanding
      cell death and other related biological processes. Although a number of possible
      roles for caspase-6 have been proposed, the identities and functions of proteins
      that interact with caspase-6 remain uncertain. In this study, we established a
      cell line expressing tandem affinity purification (TAP)-tagged caspase- 6 and
      then used LC-MS/MS proteomic analysis to analyze the caspase-6 interactome. Eight
      candidate caspase-6-interacting proteins were identified. Of these, five proteins
      (hnRNP-M, DHX38, ASPP2, MTA2, and UACA) were subsequently examined by co
      immunoprecipitation for interactions with caspase-6. Thus, we identified two
      novel members of the caspase-6 interactome: hnRNP-M and MTA2.

PMID- 24572281
TI  - Phenotypic plasticity of male Schistosoma mansoni from the peritoneal cavity and
      hepatic portal system of laboratory mice and hamsters.
AB  - Morphometric analysis of Schistosoma mansoni male worms obtained from AKR/J and
      Swiss mice was carried out. Rodents infected by the intraperitoneal route with 80
      cercariae of the schistosome (LE strain) were killed by cervical dislocation at
      45 and 60 days post-infection and both peritoneal lavage and perfusion of the
      portal system were performed for the recovery of adult worms. Characteristics
      including total body length, the distance between oral and ventral suckers,
      extension of testicular mass and the number of testes were considered in the
      morphological analysis. Changes that occurred in S. mansoni recovered from the
      peritoneal cavity or from the portal system of AKR/J and Swiss mice included
      total body length and reproductive characteristics. Significant morphometric
      alterations were also observed when worms recovered from the portal system of
      both strains of mice were compared with the schistosomes obtained from hamsters
      (Mesocricetus auratus), the vertebrate host in which the LE strain had been
      adapted and maintained by successive passages for more than four decades. The
      present results reinforce the idea that S. mansoni has high plastic potential and
      adaptive capacity. 

PMID- 24572291
TI  - Reducing pain associated with arterial punctures for blood gas analysis.
AB  - Arterial punctures for arterial blood gases (ABGs) analysis are described as the
      most painful laboratory procedure and are performed without the benefit of pain
      management. This study originated from one nurse's concern about the level of
      pain her hospitalized patients endured when she drew their ABGs. A review of the
      literature found that ABG pain relief has not been studied in hospitalized
      patients. Therefore, this study explored the question "Can the pain of arterial
      blood gas draws be reduced through the use of infiltration with a local
      anesthetic agent?" This study compared the pain scores of 40 hospitalized
      patients who received either no intervention or one of three analgesic
      interventions (infiltration of 0.7 ml 1% lidocaine, 0.7 ml buffered 1% lidocaine,
      or 0.7 ml of bacteriostatic saline at the arterial puncture site). Results showed
      that, although lidocaine and buffered lidocaine are effective in reducing the
      pain associated with the arterial puncture, plain lidocaine was the only
      intervention in which the pain rating score for the overall experience was
      significantly diminished. This study is limited by partial randomization, small
      sample size, and patient duress; however, it provides a foundation for further
      nursing research that explores methods to reduce the pain associated with this
      very painful procedure. Future studies should be directed at larger, diverse
      populations, multiple operators, and comparison of interventions to topical
      analgesics and nonpharmacological measures. 

PMID- 24572292
TI  - Ritual healing and mental health in India.
AB  - Ritual healing is very widespread in the Indian state of Uttarakhand, and is by
      far the most common option for those with serious behavioral disturbances.
      Although ritual healing thus accounts for a very large part of the actual health
      care system, the state and its regulatory agencies have, for the most part, been
      structurally blind to its existence. A decade of research on in this region,
      along with a number of shorter research trips to healing shrines and specialists
      elsewhere in the subcontinent, and a thorough study of the literature, suggest
      that such techniques are often therapeutically effective. However, several
      considerations suggest that ritual healing may not be usefully combined with
      mainstream "Western" psychiatry: (a) psychiatry is deeply influenced by the
      ideology of individualism, which is incompatible with South Asian understandings
      of the person; (b) social asymmetries between religious healers and health
      professionals are too great to allow a truly respectful relationship between
      them; and (c) neither the science of psychiatry nor the regulatory apparatus of
      the state can or will acknowledge the validity of "ritual therapy"--and even if
      they did so, regulation would most likely destroy what is most valuable about
      ritual healing. This suggests that it is best if the state maintain its
      structural blindness to ritual healing.

PMID- 24572293
TI  - A phase 1 trial of oncolytic HSV-1, G207, given in combination with radiation for
      recurrent GBM demonstrates safety and radiographic responses.
AB  - G207, a mutant herpes simplex virus (HSV) type 1, is safe when inoculated into
      recurrent malignant glioma. We conducted a phase 1 trial of G207 to demonstrate
      the safety of stereotactic intratumoral administration when given 24 hours prior
      to a single 5 Gy radiation dose in patients with recurrent malignant glioma. Nine
      patients with progressive, recurrent malignant glioma despite standard therapy
      were included. Patients received one dose of G207 stereotactically inoculated
      into the multiple sites of the enhancing tumor margin and were then treated
      focally with 5 Gy radiation. Treatment was well tolerated, and no patient
      developed HSV encephalitis. The median interval between initial diagnosis and
      G207 inoculation was 18 months (mean: 23 months; range: 11-51 months). Six of the
      nine patients had stable disease or partial response for at least one time point.
      Three instances of marked radiographic response to treatment occurred. The median
      survival time from G207 inoculation until death was 7.5 months (95% confidence
      interval: 3.0-12.7). In conclusion, this study showed the safety and the
      potential for clinical response of single-dose oncolytic HSV therapy augmented
      with radiation in the treatment of malignant glioma patients. Additional studies
      with oncolytic HSV such as G207 in the treatment of human glioma are recommended.

PMID- 24572294
TI  - Elimination of progressive mammary cancer by repeated administrations of chimeric
      antigen receptor-modified T cells.
AB  - Continuous oncogenic processes that generate cancer require an on-going treatment
      approach to eliminate the transformed cells, and prevent their further
      development. Here, we studied the ability of T cells expressing a chimeric
      antibody-based receptor (CAR) to offer a therapeutic benefit for breast cancer
      induced by erbB-2. We tested CAR-modified T cells (T-bodies) specific to erbB-2
      for their antitumor potential in a mouse model overexpressing a human erbB-2
      transgene that develops mammary tumors. Comparing the antitumor reactivity of CAR
      modified T cells under various therapeutic settings, either prophylactic, prior
      to tumor development, or therapeutically. We found that repeated administration
      of CAR-modified T cells is required to eliminate spontaneously developing mammary
      cancer. Systemic, as well as intratumoral administered CAR-modified T cells
      accumulated at tumor sites and eventually eliminated the malignant cells.
      Interestingly, within a few weeks after a single CAR T cells' administration, and
      rejection of primary lesion, tumors usually relapsed both in treated mammary
      gland and at remote sites; however, repeated injections of CAR-modified T cells
      were able to control the secondary tumors. Since spontaneous tumors can arise
      repeatedly, especially in the case of syndromes characterized by specific
      susceptibility to cancer, multiple administrations of CAR-modified T cells can
      serve to control relapsing disease. 

PMID- 24572296
TI  - The management of pemphigus vulgaris in a burn intensive care unit: a case report
      and treatment review.
AB  - Pemphigus vulgaris is a rare, potentially fatal, autoimmune blistering disease of
      the skin and mucous membranes. Treatment of this disease is problematic because
      of a lack of high-grade, evidence-based recommendations, the side-effect profiles
      of the therapies available, and the extensive supportive care that afflicted
      patients require. The authors present the unfortunate course of a patient with
      severe pemphigus vulgaris who was admitted to the U.S. Army Institute of Surgical
      Research Burn Center, to demonstrate the potential complications of therapy.
      Given the patient's complex course, the authors reviewed the literature and share
      in this article the most up-to-date treatment recommendations for patients with
      pemphigus vulgaris. The authors' review of the literature supports using
      conventional therapy consisting of high-dose corticosteroids and an adjuvant
      immunosuppressant for mild to moderate cases of pemphigus vulgaris. The
      immunosuppresants recommended are mycophenolate mofetil, azathioprine, and
      cyclophosphamide, in order of preference, based on their side-effect profiles and
      steroid-sparing effects. For severe or recalcitrant cases of pemphigus vulgaris,
      the authors recommend adding rituximab as early as possible. If increased risk of
      infection is of particular concern, the use of intravenous immunoglobulin in
      place of rituximab is advised. 

PMID- 24572295
TI  - Aptamer against mannose-capped lipoarabinomannan inhibits virulent Mycobacterium
      tuberculosis infection in mice and rhesus monkeys.
AB  - The major surface lipoglycan of Mycobacterium tuberculosis (M. tb), mannose
      capped lipoarabinomannan (ManLAM), is an immunosuppressive epitope of M. tb. We
      used systematic evolution of ligands by exponential enrichment (SELEX) to
      generate an aptamer (ZXL1) that specifically bound to ManLAM from the virulent M.
      tb strain H37Rv. Aptamer ZXL1 had the highest binding affinity, with an
      equilibrium dissociation constant (Kd) of 436.3 +/- 37.84 nmol/l, and competed
      with the mannose receptor for binding to ManLAM and M. tb H37Rv. ZXL1
      significantly inhibited the ManLAM-induced immunosuppression of CD11c(+)
      dendritic cells (DCs) and enhanced the M. tb antigen-presenting activity of DCs
      for naive CD4(+) Th1 cell activation. More importantly, we demonstrated that
      injection of aptamer ZXL1 significantly reduced the progression of M. tb H37Rv
      infections and bacterial loads in lungs of mice and rhesus monkeys. These results
      suggest that the aptamer ZXL1 is a new potential antimycobacterial agent and
      tuberculosis vaccine immune adjuvant.

PMID- 24572297
TI  - Urban epidemic of dengue virus serotype 3 infection, Senegal, 2009.
AB  - An urban epidemic of dengue in Senegal during 2009 affected 196 persons and
      included 5 cases of dengue hemorrhagic fever and 1 fatal case of dengue shock
      syndrome. Dengue virus serotype 3 was identified from all patients, and Aedes
      aegypti mosquitoes were identified as the primary vector of the virus. 

PMID- 24572298
TI  - Long-term testosterone administration affects the number of paracervical ganglion
      ovary-projecting neurons in sexually mature gilts.
AB  - The influence of testosterone (T) overdose on the number and distribution of
      ovarian neurons in the paracervical ganglion (PCG) in pigs was examined. To
      identify the ovarian neurons, on day 3 of the estrous cycle, the ovaries of both
      the control and experimental gilts were injected with retrograde neuronal tracer
      Fast Blue. From next day to the expected day 20 of the second studied cycle,
      experimental gilts were injected with T, while control gilts received oil. The
      PCG was then collected and processed for double-labeling immunofluorescence. T
      injections increased the T (~3.5-fold) and estradiol-17beta (~1.6-fold) levels in
      the peripheral blood, and reduced the following in the PCG: the total number of
      Fast Blue-positive neurons, the number of perikarya in the lateral part of the
      PCG, the numbers of VAChT(+)/SOM(+), VAChT(+)/VIP(+), VAChT(+)/nNOS(+),
      VAChT(+)/VIP(-), VAChT(+)/DbetaH(-), VAChT(-)/SOM(-), VAChT(-)/VIP(-), VAChT(
      )/nNOS(-) and VAChT(-)/DbetaH(-) perikarya, In the T-affected PCG, the
      populations of ovarian perikarya coded VAChT(-)/SOM(+), VAChT(-)/VIP(+) and
      VAChT(-)/DbetaH(+), and expressing androgen receptor were increased. After T
      treatment within the PCG dropped the density of nerve fibers expressing VAChT
      and/or SOM, VIP, DbetaH. Obtained data suggest that elevated androgen levels
      occurring during pathological processes may regulate ovary function(s) by
      affecting the PCG gonad-supplying neurons. 

PMID- 24572299
TI  - From the editor.

PMID- 24572300
TI  - Foot orthoses. The runners' frequent bane and rare boon.

PMID- 24572301
TI  - IntroductionThe injured runner.

PMID- 24572302
TI  - The biomechanics of running.
AB  - Correct diagnosis and successful treatment of running related injuries are based
      on a firm understanding of the biomechanics of running. The sports medicine
      practitioner, knowing the principles of the bone and muscular interactions of the
      structures involved in running, can generate specific, accurate diagnosis and
      detailed, individualized treatment and prevention protocols. Intrinsic
      biomechanical factors and extrinsic influences will be examined for their effects
      on running and related injuries. 

PMID- 24572303
TI  - Evaluation of the injured runner.
AB  - The evaluation of the injured runner emphasizes the identification of intrinsic
      and extrinsic risk factors in addition to establishing injury specific diagnosis.
      The history emphasizes identification of contributory changes in training regimen
      or technique. The physical examination includes a biomechanical screening to
      identify related imbalances in posture, alignment, strength, and flexibility.
      This comprehensive, running specific approach to diagnosis will assist the
      clinician in developing optimum rehabilitation programs. 

PMID- 24572304
TI  - Overload injuries in the lower extremity in runners.
AB  - This article will discuss some of the common overload injuries that occur in
      runners. An approach to accurate diagnosis will be described in terms of tissue
      injuries, clinical symptoms, specific tissues overloaded, functional
      biomechanical deficits, and functional adaptations that occur. With this
      background, specific principles of rehabilitation of these disorders will be
      described. 

PMID- 24572305
TI  - Patellofemoral pain in runners.
AB  - Patellofemoral pain is one of the most common knee disorders affecting runners.
      The vast majority of cases arc related to some degree of patellar malalignment.
      This article addresses how to assess both static and dynamic factors contributing
      to altered patellar position and lower extremity mechanics. Emphasis is given to
      the anatomic, soft tissue and strength deficits that must be considered for
      correction of patellar mal alignment and a successful rehabilitation program. 

PMID- 24572306
TI  - Spine injuries in runners: A functional approach.
AB  - Interest and participation in running has increased over the past several
      decades. There has also been a substantial increase in the incidence and
      prevalence of injuries associated with running. The etiology of running injuries
      is multifactorial. Of all the musculoskeletal injuries associated with running,
      lumbar spine injuries are among the least common - yet can be the most
      debilitating. The impact load generated during heelstrike travels up the lower
      extremity kinetic chain and converges on the lumbar spine. This impact load is
      minimized through a series of normal biomechanical actions of the joints and the
      soft tissues that support them. Dysfunction at any link in the lower extremity
      kinetic chain can set off a cascading series of mechanical adaptations throughout
      the spinal axis. Similarly, spinal pain and dysfunction can create peripheral
      joint adaptations. These mechanical adaptations may become painful or may create
      a painful dysfunction at a more distant site. There are a variety of structures
      in the lumbar spine that can cause pain. Mechanical, vascular, biochemical, and
      neurochemical factors may also be involved in the production of low back pain and
      radiculopathy. Running stresses the normal biomechanics of the lumbar spine.
      Changes in normal tissue function including strength, strength balance,
      flexibility, and proprioception may be caused by these stresses or be the cause
      of them. New adaptive functional running patterns occur. A thorough
      rehabilitation plan that addresses all aspects of the injury requires an accurate
      and complete diagnosis that is made as soon as possible. The rehabilitation
      program is divided into acute and subacute phases. Education, physical
      modalities, medication, manual therapy, traction and therapeutic exercise are
      used to help meet the goals of the acute phase of rehabilitation. The goals of
      the subacute phase are met by optimizing strength, endurance, and coordination of
      the neuromuscular system as it affects the lumbar spine and preventing any
      further injury or recurrences. Running specific rehabilitation may start early in
      the subacute phase and then progress as the runner's spine stabilization skills
      improve. 

PMID- 24572307
TI  - Stress fractures in runners.
AB  - Stress fractures, were first described in military recruits but in recent years
      have increasingly been described in runners. In most surveys they comprise
      between 10 and 20% of all running injuries. The tibia is the most common site of
      all stress fractures although recent studies involving track and field athletes
      show an increased incidence of navicular stress fractures. The diagnosis is based
      on the clinical findings of a history of exercise-related bone pain with local
      bony tenderness on examination. The diagnosis is often confirmed by a typical
      appearance on an isotope bone scan or plain radiograph. In general, treatment
      consists of relative rest from the aggravating activity until symptom-free and
      then graduated resumption of activity. Attention also needs to be paid to
      correction of possible causative factors. These include excessive training, low
      bone density, low calcium intake, menstrual abnormalities in females and
      biomechanical features such as excessive sub-talar pronation. Certain stress
      fractures, such as those in the navicular, require specific management, e.g. six
      weeks non-weight bearing cast immobilization. 

PMID- 24572310
TI  - Volume contents Volume 5 (1995).

PMID- 24572311
TI  - Prospects for mathematical crystallography.
AB  - The potential of mathematical crystallography as an emerging field is examined
      from a sociological point of view. Mathematical crystallography is unusual as an
      emerging field as it is also an old field, albeit scattered, with evidence of
      continued substantial activity. But its situation is similar to that of an
      emerging field, so we analyse it as such. Comparisons with past emergent efforts
      suggest that a new field can grow if given an economic demand for its product and
      a receptive environment. Developing a field entails developing a sense of
      identity, developing infrastructure and recruiting practitioners. 

PMID- 24572312
TI  - Effects of merohedric twinning on the diffraction pattern.
AB  - In merohedric twinning, the lattices of the individuals are perfectly overlapped
      and the presence of twinning is not easily detected from the diffraction pattern,
      especially in the case of inversion twinning (class I). In general, the
      investigator has to consider three possible structural models: a crystal with
      space-group type H and point group P, either untwinned (H model) or twinned
      through an operation t in vector space (t-H model), and an untwinned crystal with
      space group G whose point group P' is obtained as an extension of P through the
      twin operation t (G model). In 71 cases, consideration of the reflection
      conditions may directly rule out the G model; in seven other cases the reflection
      conditions suggest a space group which does not correspond to the extension of H
      by the twin operation and the structure solution or at least the refinement will
      fail. When the twin operation belongs to a different crystal family (class IIB
      twinning: the crystal has a specialized metric), the presence of twinning can
      often be recognized by the peculiar effect it has on the reflection conditions. 

PMID- 24572313
TI  - Brillouin-zone database on the Bilbao Crystallographic Server.
AB  - The Brillouin-zone database of the Bilbao Crystallographic Server
      (http://www.cryst.ehu.es) offers k-vector tables and figures which form the
      background of a classification of the irreducible representations of all 230
      space groups. The symmetry properties of the wavevectors are described by the so
      called reciprocal-space groups and this classification scheme is compared with
      the classification of Cracknell et al. [Kronecker Product Tables, Vol. 1, General
      Introduction and Tables of Irreducible Representations of Space Groups (1979).
      New York: IFI/Plenum]. The compilation provides a solution to the problems of
      uniqueness and completeness of space-group representations by specifying the
      independent parameter ranges of general and special k vectors. Guides to the k
      vector tables and figures explain the content and arrangement of the data. Recent
      improvements and modifications of the Brillouin-zone database, including new
      tables and figures for the trigonal, hexagonal and monoclinic space groups, are
      discussed in detail and illustrated by several examples. 

PMID- 24572314
TI  - On physical property tensors invariant under line groups.
AB  - The form of physical property tensors of a quasi-one-dimensional material such as
      a nanotube or a polymer can be determined from the point group of its symmetry
      group, one of an infinite number of line groups. Such forms are calculated using
      a method based on the use of trigonometric summations. With this method, it is
      shown that materials invariant under infinite subsets of line groups have
      physical property tensors of the same form. For line group types of a family of
      line groups characterized by an index n and a physical property tensor of rank m,
      the form of the tensor for all line group types indexed with n > m is the same,
      leaving only a finite number of tensor forms to be determined. 

PMID- 24572315
TI  - Direct phasing in femtosecond nanocrystallography. I. Diffraction
      characteristics.
AB  - X-ray free-electron lasers solve a number of difficulties in protein
      crystallography by providing intense but ultra-short pulses of X-rays, allowing
      collection of useful diffraction data from nanocrystals. Whereas the diffraction
      from large crystals corresponds only to samples of the Fourier amplitude of the
      molecular transform at the Bragg peaks, diffraction from very small crystals
      allows measurement of the diffraction amplitudes between the Bragg samples.
      Although highly attenuated, these additional samples offer the possibility of
      iterative phase retrieval without the use of ancillary experimental data [Spence
      et al. (2011). Opt. Express, 19, 2866-2873]. This first of a series of two papers
      examines in detail the characteristics of diffraction patterns from collections
      of nanocrystals, estimation of the molecular transform and the noise
      characteristics of the measurements. The second paper [Chen et al. (2014). Acta
      Cryst. A70, 154-161] examines iterative phase-retrieval methods for
      reconstructing molecular structures in the presence of the variable noise levels
      in such data. 

PMID- 24572316
TI  - Direct phasing in femtosecond nanocrystallography. II. Phase retrieval.
AB  - X-ray free-electron laser diffraction patterns from protein nanocrystals provide
      information on the diffracted amplitudes between the Bragg reflections, offering
      the possibility of direct phase retrieval without the use of ancillary
      experimental diffraction data [Spence et al. (2011). Opt. Express, 19, 2866
      2873]. The estimated continuous transform is highly noisy however [Chen et al.
      (2014). Acta Cryst. A70, 143-153]. This second of a series of two papers
      describes a data-selection strategy to ameliorate the effects of the high noise
      levels and the subsequent use of iterative phase-retrieval algorithms to
      reconstruct the electron density. Simulation results show that employing such a
      strategy increases the noise levels that can be tolerated. 

PMID- 24572317
TI  - Viruses and fullerenes--symmetry as a common thread?
AB  - The principle of affine symmetry is applied here to the nested fullerene cages
      (carbon onions) that arise in the context of carbon chemistry. Previous work on
      affine extensions of the icosahedral group has revealed a new organizational
      principle in virus structure and assembly. This group-theoretic framework is
      adapted here to the physical requirements dictated by carbon chemistry, and it is
      shown that mathematical models for carbon onions can be derived within this
      affine symmetry approach. This suggests the applicability of affine symmetry in a
      wider context in nature, as well as offering a novel perspective on the geometric
      principles underpinning carbon chemistry. 

PMID- 24572318
TI  - Alternative approaches to onion-like icosahedral fullerenes.
AB  - The fullerenes of the C60 series (C60, C240, C540, C960, C1500, C2160 etc.) form
      onion-like shells with icosahedral Ih symmetry. Up to C2160, their geometry has
      been optimized by Dunlap & Zope from computations according to the analytic
      density-functional theory and shown by Wardman to obey structural constraints
      derived from an affine-extended Ih group. In this paper, these approaches are
      compared with models based on crystallographic scaling transformations. To start
      with, it is shown that the 56 symmetry-inequivalent computed carbon positions,
      approximated by the corresponding ones in the models, are mutually related by
      crystallographic scalings. This result is consistent with Wardman's remark that
      the affine-extension approach simultaneously models different shells of a carbon
      onion. From the regularities observed in the fullerene models derived from
      scaling, an icosahedral infinite C60 onion molecule is defined, with shells
      consisting of all successive fullerenes of the C60 series. The structural
      relations between the C60 onion and graphite lead to a one-parameter model with
      the same Euclidean symmetry P63mc as graphite and having a c/a = tau(2) ratio,
      where tau = 1.618... is the golden number. This ratio approximates (up to a 4%
      discrepancy) the value observed in graphite. A number of tables and figures
      illustrate successive steps of the present investigation. 

PMID- 24572319
TI  - What periodicities can be found in diffraction patterns of quasicrystals?
AB  - The structure of quasicrystals is aperiodic. Their diffraction patterns, however,
      can be considered periodic. They are composed solely of series of peaks which
      exhibit a fully periodic arrangement in reciprocal space. Furthermore, the peak
      intensities in each series define the so-called 'envelope function'. A Fourier
      transform of the envelope function gives an average unit cell, whose definition
      is based on the statistical distribution of atomic coordinates in physical space.
      If such a distribution is lifted to higher-dimensional space, it becomes the so
      called atomic surface - the most fundamental feature of higher-dimensional
      analysis. 

PMID- 24572320
TI  - Symmetry of helicoidal biopolymers in the frameworks of algebraic geometry: alpha
      helix and DNA structures.
AB  - The chain of algebraic geometry and topology constructions is mapped on a
      structural level that allows one to single out a special class of discrete
      helicoidal structures. A structure that belongs to this class is locally
      periodic, topologically stable in three-dimensional Euclidean space and
      corresponds to the bifurcation domain. Singular points of its bounding minimal
      surface are related by transformations determined by symmetries of the second
      coordination sphere of the eight-dimensional crystallographic lattice E8. These
      points represent cluster vertices, whose helicoid joining determines the topology
      and structural parameters of linear biopolymers. In particular, structural
      parameters of the alpha-helix are determined by the seven-vertex face-to-face
      joining of tetrahedra with the E8 non-integer helical axis 40/11 having a
      rotation angle of 99 degrees , and the development of its surface coincides with
      the cylindrical development of the alpha-helix. Also, packing models have been
      created which determine the topology of the A, B and Z forms of DNA. 

PMID- 24572322
TI  - Laser versus non-laser stapedotomy in otosclerosis: a systematic review and meta
      analysis.
AB  - OBJECTIVE: To compare and evaluate the hearing outcome and complications of
      otosclerosis treated with the laser or non-laser stapedotomy using meta-analysis.
      METHODS: A thorough search for publications and "in-process" articles with
      English abstract dating from January 1978 to July 2013 was conducted using
      Pubmed, EBSCO and Web of Science databases, as well as all related papers. The
      included criteria were otosclerosis as diagnosis, clear description of surgical
      methods, calibrated stapedotomy and regular collection of functional results.
      Hearing results and other comparable data (age, preoperative hearing status, and
      mean length of follow-up) were collected from the articles. RESULTS: Eleven
      studies with a total of 1614 subjects were identified to meet our criteria. There
      was a significant difference in the efficacy of stapedotomy with the laser or non
      laser technique; current data showed a combined RR of 1.07 (95% CI: 1.02-1.13,
      p=0.005). But, the postoperative complication showed no advantage for the laser
      group, with a combined RR of 0.63 (95% CI: 0.30-1.34, p=0.23). Although there was
      publication bias in this study (p=0.005), the funnel plot would turn out to be
      symmetrical after six more studies were added by the trim and fill method.
      CONCLUSION: Our overall results suggest that the laser stapedotomy had
      significantly better hearing results than non-laser stapedotomy. However, current
      papers on laser and non-laser stapedotomy did not provide enough subjects to make
      a subgroup analysis of the hearing outcome between different laser groups. More
      studies reporting different laser techniques are required to provide us with a
      better understanding of laser stapedotomy.

PMID- 24572323
TI  - Early days with Carl.
AB  - Science is all about making discoveries. That's it! It was my good fortune and
      Carl's good fortune to share an experiment that produced an unexpected result. In
      the 1960s, Carl became interested in the classification of bacteria with the
      ultimate goal of defining the relatedness of bacterial groups as well as events
      in the evolution of these organisms. He proposed to do this by studying the
      sequence of monomers in proteins or nucleic acids. Study of the sequence of amino
      acids in conserved proteins had severe limitations and could not serve Carl's
      purpose. However, the publication by Sanger of a technique for analysis of RNA
      caught Carl's attention. His previous experiments with the ribosome had convinced
      him that this organelle was of very ancient origin; it had only one role in the
      cell and so was "insulated" from the vast phenotypic variations of bacterial
      cells. 

PMID- 24572325
TI  - From the editor.

PMID- 24572324
TI  - Efficacy and safety of inferior turbinates coblation in children.
AB  - OBJECTIVE: To assess the effectiveness and safety of coblation in relieving
      inferior turbinate hypertrophy in children. METHODS: An observational cohort
      study was undertaken. The severity of allergic rhinitis and the severity and
      degree of nasal obstruction were assessed using subjective and clinical symptom
      grading tools, a visual analogue scale, and endoscopy. Any post-operative
      complications were noted at 1 week, and at 1, 3, 6 and 12 months post
      operatively. Data from extended follow-up periods were included when available.
      The statistical significance of changes in parameter values was assessed using
      the Wilcoxon signed-rank test. RESULTS: Thirty-two patients were recruited (mean
      age, 11.28 years; range, 6-17 years). Significant post-operative improvement
      (p<0.001) was noted in the severity and degree of nasal obstruction. This
      improvement was maintained after a mean follow-up period of 10.5 months (range, 1
      month to 4 years). No mucosal ulceration or adhesion was encountered. Minimal
      crusting was noted in 8.57 per cent of patients at 1-week follow up. Allergic
      rhinitis symptoms improved significantly. CONCLUSION: Inferior turbinate
      reduction by coblation is an effective and safe procedure in children aged six
      years and older. The positive outcomes seem to be long-lasting.

PMID- 24572326
TI  - IntroductionThe injured runner.

PMID- 24572327
TI  - Overuse injuries of the hip and pelvis.
AB  - The runner who presents with pain in the hip and pelvis, all too often is
      approached from a one-joint or soft tissue injury concept. Since most injuries to
      this region are related to overuse and, in particular, overload injury, a
      biomechanical approach to identify significant muscle imbalances and joint
      dysfunctions must be sought. In addition, their relationship as predisposing
      factors to soft tissue injury will be emphasized in this article. A thorough
      understanding of the relationship between the lumbar spine, pelvis, hip and
      thigh, and, in particular, dysfunctions and imbalances in the lumbo-pelvic
      movements, are the most essential. Evaluation and treatment focusing on this
      concept will more likely lead to a successful long-term result and prevention of
      re-injury in a runner who is at high risk for recurrence. 

PMID- 24572328
TI  - Special considerations for the pediatric running population.
AB  - Ever greater numbers of children are participating in running sports at earlier
      ages. These children will encounter many of the same problems seen in adults, but
      will also have many unique concerns. This article was written to provide
      information to primary health care providers on the differences in risks,
      injuries, treatments, and general health concerns of the pediatric running
      population. 

PMID- 24572329
TI  - Special considerations for the female runner.
AB  - There are a number of physiologic and anatomic differences between males and
      females which affect performance and the rate of injury. In addition, there are
      several disorders which occur with some frequency in female runners - eating
      disorders and amenorrhea, which warrant review. Most pregnant runners should be
      encouraged to remain active, with appropriate medical supervision. Providing good
      medical care for female runners requires a working knowledge of their unique
      features. 

PMID- 24572330
TI  - Cross-training and periodization in running.
AB  - Understanding the principles of cross-training and periodization will assist the
      coach and team physician in designing training programs that maximize performance
      while minimizing risk of injury. Cross-training is defined as simultaneous
      training for two or more sports or the use of multiple modes of training to
      enhance performance in one particular sport. This manuscript will review the
      benefits of three commonly used forms of cross training, deep water running,
      cycling and swimming, on running, training and performance. Periodization refers
      to the process of designing a progressive and appropriate training plan in order
      to optimize performance, yet minimize injury related to overtraining. The main
      structural components for periodization are macrocycles, mesocycles and
      microcycles. Physiological determinants for distance running performance,
      including VO2 max, lactate threshold and running economy, are presented as key
      components for the design of endurance training programs. Training intensity can
      be prescribed or monitored using running speed, heart rate, and rating of
      perceived exertion (RPE). The clinician must often make recommendations regarding
      the appropriate level of training or offer an alternative. By understanding the
      principles of cross-training and periodization, the clinician can assist the
      coach or athlete in preventing injury as well as assisting the attainment of peak
      performance. 

PMID- 24572331
TI  - Distance running: Organization of a medical team.
AB  - There has been a dramatic increase in endurance race participation, which has led
      to the need for medical coverage during these events. Organization and
      preparation for the event are essential to providing thorough medical coverage.
      The medical director coordinates medical coverage and works closely with the race
      director to develop a safe and efficient race plan. Education of staff and
      participants is done before race day, as well as during the event. Triage and
      prompt treatment of injuries are the major components of race day activities.
      This chapter discusses the needs and development of medical coverage for an
      endurance event. It also describes commonly seen injuries and their initial
      treatment. Finally, it gives suggestions for staff and participant education. 

PMID- 24572333
TI  - Appendix 1.

PMID- 24572332
TI  - Running shoes and orthoses: a practical approach.
AB  - The proper selection of running shoes and judicious use of orthoses are two key
      components in addressing the intrinsic and extrinsic abnormalities that often
      result in running injuries. Sports medicine practitioners need to know how the
      function of the running shoe is effected by its components, shape, and
      construction. Shoes must fit a runner's foot type as well as size. The proper use
      of orthoses can favorably alter biomechanical abnormalities. This article
      presents a practical approach to both the selection of running shoes and the use
      of orthoses. 

PMID- 24572335
TI  - Contents of journals relating to back and musculoskeletal rehabilitation.

PMID- 24572337
TI  - Sternal bone erosion by a giant chronic aortic pseudoaneurysm in a patient with
      previous surgery for type A aortic dissection.

PMID- 24572336
TI  - Assessing THK523 selectivity for tau deposits in Alzheimer's disease and non
      Alzheimer's disease tauopathies.
AB  - INTRODUCTION: The introduction of tau imaging agents such as (18)F-THK523 offers
      new hope for the in vivo assessment of tau deposition in tauopathies such as
      Alzheimer's disease (AD), where preliminary (18)F-THK523-PET studies have
      demonstrated significantly higher cortical retention of (18)F-THK523 in AD
      compared to age-matched healthy individuals. In addition to AD, tau imaging with
      PET may also be of value in assessing non-AD tauopathies, such as corticobasal
      degeneration (CBD), progressive supranuclear palsy (PSP) and Pick's disease
      (PiD). METHODS: To further investigate the ability of THK523 to recognize tau
      lesions, we undertook immunohistochemical and fluorescence studies in serial
      brain sections taken from individuals with AD (n = 3), CBD (n = 2), PSP (n = 1),
      PiD (n = 2) and Parkinson's disease (PD; n = 2). In addition to the
      neuropathological analysis, one PSP patient had undergone a (18)F-THK523 PET scan
      5 months before death. RESULTS: Although THK523 labelled tau-containing lesions
      such as neurofibrillary tangles and neuropil threads in the hippocampus and
      frontal regions of AD brains, it failed to label tau-containing lesions in non-AD
      tauopathies. Furthermore, though THK523 faintly labelled dense-cored amyloid-beta
      plaques in the AD frontal cortex, it failed to label alpha-synuclein-containing
      Lewy bodies in PD brain sections. CONCLUSION: The results of this study suggest
      that (18)F-THK523 selectively binds to paired helical filament tau in AD brains
      but does not bind to tau lesions in non-AD tauopathies, or to alpha-synuclein in
      PD brains.

PMID- 24572338
TI  - A propensity-score matched analysis on the impact of postoperative atrial
      fibrillation on the early and late outcomes after concomitant aortic valve
      replacement and coronary artery bypass graft surgery.
AB  - BACKGROUND: Postoperative atrial fibrillation (POAF) is a known complication of
      cardiac surgery. There is a paucity of data on the effects of POAF on short-term
      and long-term outcomes after concomitant aortic valve replacement and coronary
      artery bypass grafting (AVR-CABG ). METHODS: We retrospectively reviewed data on
      patients without preexisting arrhythmia who underwent isolated first-time AVR
      CABG between June 2001 and December 2009 using the Australasian Society of
      Cardiac and Thoracic Surgeons National Cardiac Surgery Database Program.
      Preoperative characteristics, early postoperative outcomes and late survival were
      compared between patients who developed POAF and those who did not. Propensity
      score matching was performed to account for the differences between the two
      groups. RESULTS: Isolated AVR-CABG surgery was performed in 2028 patients without
      preexisting arrhythmias at 18 Australian institutions, of whom 894 (44.1%)
      developed POAF. POAF patients were generally older (mean age, 75 vs. 73 years, P
      < 0.001). From the initial study population, 715 propensity-matched patient-pairs
      were derived; the overall matching rate was 80.0%. In the matched groups, 30-day
      mortality was similar in both groups (3.5 vs. 2.1%, P = 0.16). Patients with
      POAF, however, were more likely to develop perioperative complications, including
      new renal failure, prolonged ventilation (>24 h), multisystem failure and
      readmission within 30 days of surgery (all P < 0.05). Patients with POAF also had
      a significantly greater length of hospital stay (P < 0.001). Seven-year survival
      was not significantly different between the two groups (72 vs. 75%, P = 0.11).
      CONCLUSION: POAF was not associated with an increased risk of early or late
      mortality. It is, however, associated with poorer perioperative outcomes. It is
      important to evaluate potential treatment strategies for POAF.

PMID- 24572339
TI  - Personality traits, cardiac risk factors, and their association with presence and
      severity of coronary artery plaque in people with no history of cardiovascular
      disease.
AB  - BACKGROUND: Coronary artery disease (CAD) is a multifactorial complex disease.
      The aim of the present study is to verify whether the personality traits in CAD
      are associated with coronary artery plaque (CAP) presence and severity in people
      with no history of cardiovascular disease. DESIGN: A cross-sectional monocenter
      study. METHODS: Seventy five individuals with no history of CAD underwent 64
      slice computed tomography coronary angiography (CTCA) and were screened for
      traditional cardiac risk factors and for hostility, anger, and type D personality
      traits. RESULTS: In total, 48 patients (64%) had evidence of CAP, with mild
      (31%), moderate (33%), and severe (35%) coronary stenosis. Male sex,
      hypertension, being overweight, and number of cardiovascular risk factors
      increased the likelihood of CAP presence. Findings showed a significant
      difference between CAP presence vs. CAP absence for anger (26 vs. 30%, chi2 =
      6.82) and type D personality (23 vs. 35%; chi2 = 8.23, P = 0.03), but not
      hostility (P > 0.05). Anger personality, and the type D subscale social
      inhibition, but not negative affectivity, were associated with an increased
      prevalence and severity of CAP. Univariate analysis confirms anger (odds ratio,
      OR = 1.38, 95% confidence interval, CI = 1.12-2.31), social inhibition (OR =
      2.01, 95% CI = 1.81-2.93), 'negative affectivity by social inhibition' (OR =
      1.24, 95% CI = 1.12-2.14), and type D personality (OR = 1.9, 95% CI = 1.11-2.03)
      as predictors of CAP presence. Moreover, multivariate analysis suggests social
      inhibition as also a unique CAP predictor (OR = 2.14, 95% CI = 1.89-2.96) after
      adjustment for having cardiac risk factors as a covariate. CONCLUSION: The
      present data confirm the core role of traditional risk factors and suggest the
      primacy of social inhibition and anger personality traits in association with CAP
      presence and severity.

PMID- 24572352
TI  - The remnant of a merger between two dwarf galaxies in Andromeda II.
AB  - Driven by gravity, massive structures like galaxies and clusters of galaxies are
      believed to grow continuously through hierarchical merging and accretion of
      smaller systems. Observational evidence of accretion events is provided by the
      coherent stellar streams crossing the outer haloes of massive galaxies, such as
      the Milky Way or Andromeda. At similar mass scales, around 10(11) solar masses in
      stars, further evidence of merging activity is also ample. Mergers of lower-mass
      galaxies are expected within the hierarchical process of galaxy formation, but
      have hitherto not been seen for galaxies with less than about 10(9) solar masses
      in stars. Here we report the kinematic detection of a stellar stream in one of
      the satellite galaxies of Andromeda, the dwarf spheroidal Andromeda II, which has
      a mass of only 10(7) solar masses in stars. The properties of the stream show
      that we are observing the remnant of a merger between two dwarf galaxies. This
      had a drastic influence on the dynamics of the remnant, which is now rotating
      around its projected major axis. The stellar stream in Andromeda II illustrates
      the scale-free character of the formation of galaxies, down to the lowest
      galactic mass scales. 

PMID- 24572355
TI  - Influenza: Prediction is worth a shot.

PMID- 24572353
TI  - Detection and replication of epistasis influencing transcription in humans.
AB  - Epistasis is the phenomenon whereby one polymorphism's effect on a trait depends
      on other polymorphisms present in the genome. The extent to which epistasis
      influences complex traits and contributes to their variation is a fundamental
      question in evolution and human genetics. Although often demonstrated in
      artificial gene manipulation studies in model organisms, and some examples have
      been reported in other species, few examples exist for epistasis among natural
      polymorphisms in human traits. Its absence from empirical findings may simply be
      due to low incidence in the genetic control of complex traits, but an alternative
      view is that it has previously been too technically challenging to detect owing
      to statistical and computational issues. Here we show, using advanced computation
      and a gene expression study design, that many instances of epistasis are found
      between common single nucleotide polymorphisms (SNPs). In a cohort of 846
      individuals with 7,339 gene expression levels measured in peripheral blood, we
      found 501 significant pairwise interactions between common SNPs influencing the
      expression of 238 genes (P < 2.91 * 10(-16)). Replication of these interactions
      in two independent data sets showed both concordance of direction of epistatic
      effects (P = 5.56 * 10(-31)) and enrichment of interaction P values, with 30
      being significant at a conservative threshold of P < 9.98 * 10(-5). Forty-four of
      the genetic interactions are located within 5 megabases of regions of known
      physical chromosome interactions (P = 1.8 * 10(-10)). Epistatic networks of three
      SNPs or more influence the expression levels of 129 genes, whereby one cis-acting
      SNP is modulated by several trans-acting SNPs. For example, MBNL1 is influenced
      by an additive effect at rs13069559, which itself is masked by trans-SNPs on 14
      different chromosomes, with nearly identical genotype-phenotype maps for each cis
      trans interaction. This study presents the first evidence, to our knowledge, for
      many instances of segregating common polymorphisms interacting to influence human
      traits. 

PMID- 24572354
TI  - Mouse liver repopulation with hepatocytes generated from human fibroblasts.
AB  - Human induced pluripotent stem cells (iPSCs) have the capability of
      revolutionizing research and therapy of liver diseases by providing a source of
      hepatocytes for autologous cell therapy and disease modelling. However, despite
      progress in advancing the differentiation of iPSCs into hepatocytes (iPSC-Heps)
      in vitro, cells that replicate the ability of human primary adult hepatocytes
      (aHeps) to proliferate extensively in vivo have not been reported. This
      deficiency has hampered efforts to recreate human liver diseases in mice, and has
      cast doubt on the potential of iPSC-Heps for liver cell therapy. The reason is
      that extensive post-transplant expansion is needed to establish and sustain a
      therapeutically effective liver cell mass in patients, a lesson learned from
      clinical trials of aHep transplantation. Here, as a solution to this problem, we
      report the generation of human fibroblast-derived hepatocytes that can repopulate
      mouse livers. Unlike current protocols for deriving hepatocytes from human
      fibroblasts, ours did not generate iPSCs but cut short reprogramming to
      pluripotency to generate an induced multipotent progenitor cell (iMPC) state from
      which endoderm progenitor cells and subsequently hepatocytes (iMPC-Heps) could be
      efficiently differentiated. For this purpose we identified small molecules that
      aided endoderm and hepatocyte differentiation without compromising proliferation.
      After transplantation into an immune-deficient mouse model of human liver
      failure, iMPC-Heps proliferated extensively and acquired levels of hepatocyte
      function similar to those of aHeps. Unfractionated iMPC-Heps did not form
      tumours, most probably because they never entered a pluripotent state. Our
      results establish the feasibility of significant liver repopulation of mice with
      human hepatocytes generated in vitro, which removes a long-standing roadblock on
      the path to autologous liver cell therapy. 

PMID- 24572356
TI  - Disclinations provide the missing mechanism for deforming olivine-rich rocks in
      the mantle.
AB  - Mantle flow involves large strains of polymineral aggregates. The strongly
      anisotropic plastic response of each individual grain in the aggregate results
      from the interactions between neighbouring grains and the continuity of material
      displacement across the grain boundaries. Orthorhombic olivine, which is the
      dominant mineral phase of the Earth's upper mantle, does not exhibit enough slip
      systems to accommodate a general deformation state by intracrystalline slip
      without inducing damage. Here we show that a more general description of the
      deformation process that includes the motion of rotational defects referred to as
      disclinations can solve the olivine deformation paradox. We use high-resolution
      electron backscattering diffraction (EBSD) maps of deformed olivine aggregates to
      resolve the disclinations. The disclinations are found to decorate grain
      boundaries in olivine samples deformed experimentally and in nature. We present a
      disclination-based model of a high-angle tilt boundary in olivine, which
      demonstrates that an applied shear induces grain-boundary migration through
      disclination motion. This new approach clarifies grain-boundary-mediated
      plasticity in polycrystalline aggregates. By providing the missing mechanism for
      describing plastic flow in olivine, this work will permit multiscale modelling of
      the rheology of the upper mantle, from the atomic scale to the scale of the flow.

PMID- 24572357
TI  - The hippocampal CA2 region is essential for social memory.
AB  - The hippocampus is critical for encoding declarative memory, our repository of
      knowledge of who, what, where and when. Mnemonic information is processed in the
      hippocampus through several parallel routes involving distinct subregions. In the
      classic trisynaptic pathway, information proceeds from entorhinal cortex (EC) to
      dentate gyrus to CA3 and then to CA1, the main hippocampal output. Genetic
      lesions of EC (ref. 3) and hippocampal dentate gyrus (ref. 4), CA3 (ref. 5) and
      CA1 (ref. 6) regions have revealed their distinct functions in learning and
      memory. In contrast, little is known about the role of CA2, a relatively small
      area interposed between CA3 and CA1 that forms the nexus of a powerful disynaptic
      circuit linking EC input with CA1 output. Here we report a novel transgenic mouse
      line that enabled us to selectively examine the synaptic connections and
      behavioural role of the CA2 region in adult mice. Genetically targeted
      inactivation of CA2 pyramidal neurons caused a pronounced loss of social memory-
      the ability of an animal to remember a conspecific--with no change in sociability
      or several other hippocampus-dependent behaviours, including spatial and
      contextual memory. These behavioural and anatomical results thus reveal CA2 as a
      critical hub of sociocognitive memory processing.

PMID- 24572358
TI  - A dedicated circuit links direction-selective retinal ganglion cells to the
      primary visual cortex.
AB  - How specific features in the environment are represented within the brain is an
      important unanswered question in neuroscience. A subset of retinal neurons,
      called direction-selective ganglion cells (DSGCs), are specialized for detecting
      motion along specific axes of the visual field. Despite extensive study of the
      retinal circuitry that endows DSGCs with their unique tuning properties, their
      downstream circuitry in the brain and thus their contribution to visual
      processing has remained unclear. In mice, several different types of DSGCs
      connect to the dorsal lateral geniculate nucleus (dLGN), the visual thalamic
      structure that harbours cortical relay neurons. Whether direction-selective
      information computed at the level of the retina is routed to cortical circuits
      and integrated with other visual channels, however, is unknown. Here we show that
      there is a di-synaptic circuit linking DSGCs with the superficial layers of the
      primary visual cortex (V1) by using viral trans-synaptic circuit mapping and
      functional imaging of visually driven calcium signals in thalamocortical axons.
      This circuit pools information from several types of DSGCs, converges in a
      specialized subdivision of the dLGN, and delivers direction-tuned and orientation
      tuned signals to superficial V1. Notably, this circuit is anatomically segregated
      from the retino-geniculo-cortical pathway carrying non-direction-tuned visual
      information to deeper layers of V1, such as layer 4. Thus, the mouse harbours
      several functionally specialized, parallel retino-geniculo-cortical pathways, one
      of which originates with retinal DSGCs and delivers direction- and orientation
      tuned information specifically to the superficial layers of the primary visual
      cortex. These data provide evidence that direction and orientation selectivity of
      some V1 neurons may be influenced by the activation of DSGCs. 

PMID- 24572360
TI  - Cancer: Inflammation lights the way to metastasis.

PMID- 24572359
TI  - A cascade of DNA-binding proteins for sexual commitment and development in
      Plasmodium.
AB  - Commitment to and completion of sexual development are essential for malaria
      parasites (protists of the genus Plasmodium) to be transmitted through
      mosquitoes. The molecular mechanism(s) responsible for commitment have been
      hitherto unknown. Here we show that PbAP2-G, a conserved member of the
      apicomplexan AP2 (ApiAP2) family of DNA-binding proteins, is essential for the
      commitment of asexually replicating forms to sexual development in Plasmodium
      berghei, a malaria parasite of rodents. PbAP2-G was identified from mutations in
      its encoding gene, PBANKA_143750, which account for the loss of sexual
      development frequently observed in parasites transmitted artificially by blood
      passage. Systematic gene deletion of conserved ApiAP2 genes in Plasmodium
      confirmed the role of PbAP2-G and revealed a second ApiAP2 member (PBANKA_103430,
      here termed PbAP2-G2) that significantly modulates but does not abolish
      gametocytogenesis, indicating that a cascade of ApiAP2 proteins are involved in
      commitment to the production and maturation of gametocytes. The data suggest a
      mechanism of commitment to gametocytogenesis in Plasmodium consistent with a
      positive feedback loop involving PbAP2-G that could be exploited to prevent the
      transmission of this pernicious parasite. 

PMID- 24572361
TI  - Plant science: How to switch affinity.

PMID- 24572362
TI  - Crystal structure of the plant dual-affinity nitrate transporter NRT1.1.
AB  - Nitrate is a primary nutrient for plant growth, but its levels in soil can
      fluctuate by several orders of magnitude. Previous studies have identified
      Arabidopsis NRT1.1 as a dual-affinity nitrate transporter that can take up
      nitrate over a wide range of concentrations. The mode of action of NRT1.1 is
      controlled by phosphorylation of a key residue, Thr 101; however, how this post
      translational modification switches the transporter between two affinity states
      remains unclear. Here we report the crystal structure of unphosphorylated NRT1.1,
      which reveals an unexpected homodimer in the inward-facing conformation. In this
      low-affinity state, the Thr 101 phosphorylation site is embedded in a pocket
      immediately adjacent to the dimer interface, linking the phosphorylation status
      of the transporter to its oligomeric state. Using a cell-based fluorescence
      resonance energy transfer assay, we show that functional NRT1.1 dimerizes in the
      cell membrane and that the phosphomimetic mutation of Thr 101 converts the
      protein into a monophasic high-affinity transporter by structurally decoupling
      the dimer. Together with analyses of the substrate transport tunnel, our results
      establish a phosphorylation-controlled dimerization switch that allows NRT1.1 to
      uptake nitrate with two distinct affinity modes. 

PMID- 24572364
TI  - Earth science: Missing link in mantle dynamics.

PMID- 24572363
TI  - IL-35-producing B cells are critical regulators of immunity during autoimmune and
      infectious diseases.
AB  - B lymphocytes have critical roles as positive and negative regulators of
      immunity. Their inhibitory function has been associated primarily with
      interleukin 10 (IL-10) because B-cell-derived IL-10 can protect against
      autoimmune disease and increase susceptibility to pathogens. Here we identify IL
      35-producing B cells as key players in the negative regulation of immunity. Mice
      in which only B cells did not express IL-35 lost their ability to recover from
      the T-cell-mediated demyelinating autoimmune disease experimental autoimmune
      encephalomyelitis (EAE). In contrast, these mice displayed a markedly improved
      resistance to infection with the intracellular bacterial pathogen Salmonella
      enterica serovar Typhimurium as shown by their superior containment of the
      bacterial growth and their prolonged survival after primary infection, and upon
      secondary challenge, compared to control mice. The increased immunity found in
      mice lacking IL-35 production by B cells was associated with a higher activation
      of macrophages and inflammatory T cells, as well as an increased function of B
      cells as antigen-presenting cells (APCs). During Salmonella infection, IL-35- and
      IL-10-producing B cells corresponded to two largely distinct sets of surface
      IgM(+)CD138(hi)TACI(+)CXCR4(+)CD1d(int)Tim1(int) plasma cells expressing the
      transcription factor Blimp1 (also known as Prdm1). During EAE, CD138(+) plasma
      cells were also the main source of B-cell-derived IL-35 and IL-10. Collectively,
      our data show the importance of IL-35-producing B cells in regulation of immunity
      and highlight IL-35 production by B cells as a potential therapeutic target for
      autoimmune and infectious diseases. This study reveals the central role of
      activated B cells, particularly plasma cells, and their production of cytokines
      in the regulation of immune responses in health and disease. 

PMID- 24572365
TI  - Ultraviolet-radiation-induced inflammation promotes angiotropism and metastasis
      in melanoma.
AB  - Intermittent intense ultraviolet (UV) exposure represents an important
      aetiological factor in the development of malignant melanoma. The ability of UV
      radiation to cause tumour-initiating DNA mutations in melanocytes is now firmly
      established, but how the microenvironmental effects of UV radiation influence
      melanoma pathogenesis is not fully understood. Here we report that repetitive UV
      exposure of primary cutaneous melanomas in a genetically engineered mouse model
      promotes metastatic progression, independent of its tumour-initiating effects. UV
      irradiation enhanced the expansion of tumour cells along abluminal blood vessel
      surfaces and increased the number of lung metastases. This effect depended on the
      recruitment and activation of neutrophils, initiated by the release of high
      mobility group box 1 (HMGB1) from UV-damaged epidermal keratinocytes and driven
      by Toll-like receptor 4 (TLR4). The UV-induced neutrophilic inflammatory response
      stimulated angiogenesis and promoted the ability of melanoma cells to migrate
      towards endothelial cells and use selective motility cues on their surfaces. Our
      results not only reveal how UV irradiation of epidermal keratinocytes is sensed
      by the innate immune system, but also show that the resulting inflammatory
      response catalyses reciprocal melanoma-endothelial cell interactions leading to
      perivascular invasion, a phenomenon originally described as angiotropism in human
      melanomas by histopathologists. Angiotropism represents a hitherto
      underappreciated mechanism of metastasis that also increases the likelihood of
      intravasation and haematogenous dissemination. Consistent with our findings,
      ulcerated primary human melanomas with abundant neutrophils and reactive
      angiogenesis frequently show angiotropism and a high risk for metastases. Our
      work indicates that targeting the inflammation-induced phenotypic plasticity of
      melanoma cells and their association with endothelial cells represent rational
      strategies to specifically interfere with metastatic progression. 

PMID- 24572366
TI  - Molecular basis of nitrate uptake by the plant nitrate transporter NRT1.1.
AB  - The NRT1/PTR family of proton-coupled transporters are responsible for nitrogen
      assimilation in eukaryotes and bacteria through the uptake of peptides. However,
      in most plant species members of this family have evolved to transport nitrate as
      well as additional secondary metabolites and hormones. In response to falling
      nitrate levels, NRT1.1 is phosphorylated on an intracellular threonine that
      switches the transporter from a low-affinity to high-affinity state. Here we
      present both the apo and nitrate-bound crystal structures of Arabidopsis thaliana
      NRT1.1, which together with in vitro binding and transport data identify a key
      role for His 356 in nitrate binding. Our data support a model whereby
      phosphorylation increases structural flexibility and in turn the rate of
      transport. Comparison with peptide transporters further reveals how the NRT1/PTR
      family has evolved to recognize diverse nitrogenous ligands, while maintaining
      elements of a conserved coupling mechanism within this superfamily of nutrient
      transporters. 

PMID- 24572367
TI  - A predictive fitness model for influenza.
AB  - The seasonal human influenza A/H3N2 virus undergoes rapid evolution, which
      produces significant year-to-year sequence turnover in the population of
      circulating strains. Adaptive mutations respond to human immune challenge and
      occur primarily in antigenic epitopes, the antibody-binding domains of the viral
      surface protein haemagglutinin. Here we develop a fitness model for
      haemagglutinin that predicts the evolution of the viral population from one year
      to the next. Two factors are shown to determine the fitness of a strain: adaptive
      epitope changes and deleterious mutations outside the epitopes. We infer both
      fitness components for the strains circulating in a given year, using population
      genetic data of all previous strains. From fitness and frequency of each strain,
      we predict the frequency of its descendent strains in the following year. This
      fitness model maps the adaptive history of influenza A and suggests a principled
      method for vaccine selection. Our results call for a more comprehensive
      epidemiology of influenza and other fast-evolving pathogens that integrates
      antigenic phenotypes with other viral functions coupled by genetic linkage. 

PMID- 24572371
TI  - Toward an understanding of the effects of agitation and aeration on growth and
      laccases production by Pleurotus ostreatus.
AB  - Mycelial growth and laccase production by Pleurotus ostreatus CP50 cultured in a
      10-L mechanically agitated bioreactor were assessed through a 2(3) factorial
      experimental design. The main effects and interactions of three factors
      (agitation, aeration and copper induction) over five responses (MU, alphaLacc,
      betaLacc, maximal volumetric laccase activity and maximal biomass concentration)
      were analyzed. P. ostreatus growth was significantly improved when culturing was
      conducted with high agitation (5.9kW/m(3)s) and aeration flow (0.5vvm) rates.
      Under the experimental conditions evaluated, no evidence of hydrodynamic stress
      affecting fungal growth was observed. However, the high agitation and aeration
      conditions were detrimental for the growth-associated laccase production constant
      (alphaLacc), leading to a very complex optimization of the process. The maximal
      laccase volumetric activity (1.2 and 3.8U/ml for non-induced and copper-induced
      cultures, respectively) was observed when the culturing was performed at a low
      agitation rate (0.9kW/m(3)s) and a high aeration flow rate (0.5vvm). Laccase
      proteolysis may explain the complex interactions observed between agitation and
      aeration and the effects of these factors on the laccase volumetric activity
      observed in the cultures. 

PMID- 24572370
TI  - The reconstructive microsurgery ladder in orthopedics.

PMID- 24572369
TI  - A transcriptional switch underlies commitment to sexual development in malaria
      parasites.
AB  - The life cycles of many parasites involve transitions between disparate host
      species, requiring these parasites to go through multiple developmental stages
      adapted to each of these specialized niches. Transmission of malaria parasites
      (Plasmodium spp.) from humans to the mosquito vector requires differentiation
      from asexual stages replicating within red blood cells into non-dividing male and
      female gametocytes. Although gametocytes were first described in 1880, our
      understanding of the molecular mechanisms involved in commitment to gametocyte
      formation is extremely limited, and disrupting this critical developmental
      transition remains a long-standing goal. Here we show that expression levels of
      the DNA-binding protein PfAP2-G correlate strongly with levels of gametocyte
      formation. Using independent forward and reverse genetics approaches, we
      demonstrate that PfAP2-G function is essential for parasite sexual
      differentiation. By combining genome-wide PfAP2-G cognate motif occurrence with
      global transcriptional changes resulting from PfAP2-G ablation, we identify early
      gametocyte genes as probable targets of PfAP2-G and show that their regulation by
      PfAP2-G is critical for their wild-type level expression. In the asexual blood
      stage parasites pfap2-g appears to be among a set of epigenetically silenced loci
      prone to spontaneous activation. Stochastic activation presents a simple
      mechanism for a low baseline of gametocyte production. Overall, these findings
      identify PfAP2-G as a master regulator of sexual-stage development in malaria
      parasites and mark the first discovery of a transcriptional switch controlling a
      differentiation decision in protozoan parasites. 

PMID- 24572368
TI  - Mechanism of Tc toxin action revealed in molecular detail.
AB  - Tripartite Tc toxin complexes of bacterial pathogens perforate the host membrane
      and translocate toxic enzymes into the host cell, including in humans. The
      underlying mechanism is complex but poorly understood. Here we report the first,
      to our knowledge, high-resolution structures of a TcA subunit in its prepore and
      pore state and of a complete 1.7 megadalton Tc complex. The structures reveal
      that, in addition to a translocation channel, TcA forms four receptor-binding
      sites and a neuraminidase-like region, which are important for its host
      specificity. pH-induced opening of the shell releases an entropic spring that
      drives the injection of the TcA channel into the membrane. Binding of TcB/TcC to
      TcA opens a gate formed by a six-bladed beta-propeller and results in a
      continuous protein translocation channel, whose architecture and properties
      suggest a novel mode of protein unfolding and translocation. Our results allow us
      to understand key steps of infections involving Tc toxins at the molecular level.

PMID- 24572372
TI  - Citrus tristeza virus-based RNAi in citrus plants induces gene silencing in
      Diaphorina citri, a phloem-sap sucking insect vector of citrus greening disease
      (Huanglongbing).
AB  - A transient expression vector based on Citrus tristeza virus (CTV) is unusually
      stable. Because of its stability it is being considered for use in the field to
      control Huanglongbing (HLB), which is caused by Candidatus Liberibacter asiaticus
      (CLas) and vectored by Asian citrus psyllid, Diaphorina citri. In the absence of
      effective control strategies for CLas, emphasis has been on control of D. citri.
      Coincident cohabitation in phloem tissue by CLas, D. citri and CTV was exploited
      to develop a novel method to mitigate HLB through RNA interference (RNAi). Since
      CTV has three RNA silencing suppressors, it was not known if CTV-based vector
      could induce RNAi in citrus. Yet, expression of sequences targeting citrus
      phytoene desaturase gene by CTV-RNAi resulted in photo-bleaching phenotype. CTV
      RNAi vector, engineered with truncated abnormal wing disc (Awd) gene of D. citri,
      induced altered Awd expression when silencing triggers ingested by feeding D.
      citri nymphs. Decreased Awd in nymphs resulted in malformed-wing phenotype in
      adults and increased adult mortality. This impaired ability of D. citri to fly
      would potentially limit the successful vectoring of CLas bacteria between citrus
      trees in the grove. CTV-RNAi vector would be relevant for fast-track screening of
      candidate sequences for RNAi-mediated pest control. 

PMID- 24572373
TI  - IgG against dengue virus in healthy blood donors, Zanzibar, Tanzania.
AB  - We conducted a seroprevalence survey among 500 healthy adult donors at Zanzibar
      National Blood Transfusion Services. Dengue virus IgG seroprevalence was 50.6%
      and independently associated with age and urban residence. These data will aid in
      building a surveillance, preparedness, and response plan for dengue virus
      infections in the Zanzibar Archipelago. 

PMID- 24572374
TI  - Peripheral microcirculatory exploration during mechanical ventilation weaning.
AB  - BACKGROUND: Weaning from mechanical ventilation is a daily challenge in intensive
      care patients. Our objective was to explore microcirculatory perfusion during
      mechanical ventilation weaning and to evaluate its predictive value on the
      weaning outcome. METHODS: Prospective observational study. All consecutive
      patients, older than 18 years, under mechanical ventilation that met the criteria
      for weaning were enrolled. Patients underwent a T-piece Spontaneous Breath Trial
      (SBT) for 60 minutes and the usual clinical parameters were recorded every 5
      minutes. Microcirculatory perfusion was evaluated using the mottling score and
      the Tissue Oxygen Saturation (StO2) measured by Near Infrared Spectroscopy
      technology on the thenar and knee area. RESULTS: Seventy-three patients were
      studied (age: 67+/-15 years, men: 40, SAPS II: 47+/-15) after a duration of
      mechanical ventilation of 3 (1-6) days. Forty-five patients succeeded the first
      SBT. The mottling score severity recorded just before ventilator disconnection
      (baseline) was associated with weaning failure (P=0.03). Moreover, the mottling
      score increase during SBT was significantly associated with weaning failure (80%
      vs. 28%, P=0.001; Odds ratio 10.5 [2.0-54.8]). Baseline thenar StO2 was not
      different according to weaning outcome (failure 76+/-13% vs. success 77+/-7%,
      P=0.90) whereas baseline knee StO2 was significantly lower in patients who failed
      the first SBT (67+/-13% vs. 75+/-12%, P<0.01). This difference was apparent since
      the very beginning of the SBT and lasted throughout the trial (P=0.0001).
      CONCLUSION: In unselected mechanically ventilated patients undergoing SBT,
      mottling score and knee StO2 are early predictors of weaning failure.

PMID- 24572375
TI  - Molecular phylogenetics before sequences: oligonucleotide catalogs as k-mer
      spectra.
AB  - From 1971 to 1985, Carl Woese and colleagues generated oligonucleotide catalogs
      of 16S/18S rRNAs from more than 400 organisms. Using these incomplete and
      imperfect data, Carl and his colleagues developed unprecedented insights into the
      structure, function, and evolution of the large RNA components of the
      translational apparatus. They recognized a third domain of life, revealed the
      phylogenetic backbone of bacteria (and its limitations), delineated taxa, and
      explored the tempo and mode of microbial evolution. For these discoveries to have
      stood the test of time, oligonucleotide catalogs must carry significant
      phylogenetic signal; they thus bear re-examination in view of the current
      interest in alignment-free phylogenetics based on k-mers. Here we consider the
      aims, successes, and limitations of this early phase of molecular phylogenetics.
      We computationally generate oligonucleotide sets (e-catalogs) from 16S/18S rRNA
      sequences, calculate pairwise distances between them based on D 2 statistics,
      compute distance trees, and compare their performance against alignment-based and
      k-mer trees. Although the catalogs themselves were superseded by full-length
      sequences, this stage in the development of computational molecular biology
      remains instructive for us today. 

PMID- 24572377
TI  - Synthesis and anti-influenza activities of novel baicalein analogs.
AB  - A series of novel flavones derivatives were synthesized based on modification of
      the active ingredients of a traditional Chinese medicine Scutellaria baicalensis
      GEORGI and screened for anti-influenza activity. The synthetic baicalein
      (flavone) analogs, especially with the B-rings substituted with bromine atoms,
      were much more potent than oseltamivir or ribavirin against H1N1 Tamiflu
      resistant (H1N1 TR) virus and usually with more favorable selectivity. The most
      promising were 5b, 5c, 6b and 6c, all displaying an 50% effective concentration
      (EC50) at around 4.0-4.5 uM, and a selective index (SI=50% cytotoxic
      concentration (CC50)/EC50)>70. For seasonal H3N2-infected influenza virus, both
      5a and 5b with SI >17.3 indicated superior to ribavirin. The flavonoids having
      both not-naturally-occurring bromo-substituted B-rings and appropriate hydroxyls
      positioning on the A-rings might be critical in determining the activity and
      selectivity against H1N1-Tamiflu-resistant infected influenza viruses. 

PMID- 24572376
TI  - p16INK4a and its regulator miR-24 link senescence and chondrocyte terminal
      differentiation-associated matrix remodeling in osteoarthritis.
AB  - INTRODUCTION: Recent evidence suggests that tissue accumulation of senescent
      p16INK4a-positive cells during the life span would be deleterious for tissue
      functions and could be the consequence of inherent age-associated disorders.
      Osteoarthritis (OA) is characterized by the accumulation of chondrocytes
      expressing p16INK4a and markers of the senescence-associated secretory phenotype
      (SASP), including the matrix remodeling metalloproteases MMP1/MMP13 and pro
      inflammatory cytokines interleukin-8 (IL-8) and IL-6. Here, we evaluated the role
      of p16INK4a in the OA-induced SASP and its regulation by microRNAs (miRs).
      METHODS: We used IL-1-beta-treated primary OA chondrocytes cultured in three
      dimensional setting or mesenchymal stem cells differentiated into chondrocyte to
      follow p16INK4a expression. By transient transfection experiments and the use of
      knockout mice, we validate p16INK4a function in chondrocytes and its regulation
      by one miR identified by means of a genome-wide miR-array analysis. RESULTS:
      p16INK4a is induced upon IL-1-beta treatment and also during in vitro
      chondrogenesis. In the mouse model, Ink4a locus favors in vivo the proportion of
      terminally differentiated chondrocytes. When overexpressed in chondrocytes,
      p16INK4a is sufficient to induce the production of the two matrix remodeling
      enzymes, MMP1 and MMP13, thus linking senescence with OA pathogenesis and bone
      development. We identified miR-24 as a negative regulator of p16INK4a.
      Accordingly, p16INK4a expression increased while miR-24 level was repressed upon
      IL-1-beta addition, in OA cartilage and during in vitro terminal chondrogenesis.
      CONCLUSIONS: We disclosed herein a new role of the senescence marker p16INK4a and
      its regulation by miR-24 during OA and terminal chondrogenesis.

PMID- 24572378
TI  - Survival improvement by decade of patients aged 0-14 years with acute
      lymphoblastic leukemia: a SEER analysis.
AB  - To evaluate treatment outcomes in children with acute lymphoblastic leukemia
      (ALL) over the past 3 decades, we assessed the survival of children with ALL in
      the Surveillance, Epidemiology, and End Results (SEER) database. Among 12,096
      patients from 18 SEER sites diagnosed from 1981 to 2010, survival rates improved
      each decade from 74.8% to 84.5% to 88.6% at 5 years and from 69.3% to 80.9% to
      85.5% at 10 years (P < 0.0001). For ages 10-14 years, 10-year survival increased
      by more than 20 percentage points to 75.3%, but for infants, it remained low at
      54.7%. Improvements in survival rates were observed in both sexes, but survival
      rates were higher in girls than in boys. For ages 0-14 years during the 2001-2010
      period, the 10-year relative survival rates were 87.8% in girls and 83.6% in boys
      (P < 0.01). Survival rates in child with ALL are expected to further improve with
      continuous advance in therapies such as targeted therapy and personalized
      therapy. 

PMID- 24572381
TI  - From the editor.

PMID- 24572380
TI  - Influence of radiation dose and iterative reconstruction algorithms for
      measurement accuracy and reproducibility of pulmonary nodule volumetry: A phantom
      study.
AB  - PURPOSE: To evaluate the influence of radiation dose settings and reconstruction
      algorithms on the measurement accuracy and reproducibility of semi-automated
      pulmonary nodule volumetry. MATERIALS AND METHODS: CT scans were performed on a
      chest phantom containing various nodules (10 and 12mm; +100, -630 and -800HU) at
      120kVp with tube current-time settings of 10, 20, 50, and 100mAs. Each CT was
      reconstructed using filtered back projection (FBP), iDose(4) and iterative model
      reconstruction (IMR). Semi-automated volumetry was performed by two radiologists
      using commercial volumetry software for nodules at each CT dataset. Noise,
      contrast-to-noise ratio and signal-to-noise ratio of CT images were also
      obtained. The absolute percentage measurement errors and differences were then
      calculated for volume and mass. The influence of radiation dose and
      reconstruction algorithm on measurement accuracy, reproducibility and objective
      image quality metrics was analyzed using generalized estimating equations.
      RESULTS: Measurement accuracy and reproducibility of nodule volume and mass were
      not significantly associated with CT radiation dose settings or reconstruction
      algorithms (p>0.05). Objective image quality metrics of CT images were superior
      in IMR than in FBP or iDose(4) at all radiation dose settings (p<0.05).
      CONCLUSION: Semi-automated nodule volumetry can be applied to low- or ultralow
      dose chest CT with usage of a novel iterative reconstruction algorithm without
      losing measurement accuracy and reproducibility.

PMID- 24572382
TI  - Headache in the elderly.
AB  - Aging is accompanied by a decline in the incidence of most primary headache
      disorders and an increase in the incidence of organic causes of headache.
      Headaches that begin after age 55 are more often due to serious conditions, or
      are exacerbated by comorbid disorders. When evaluating the older patient with new
      onset headache or a change in headache pattern, one must rule out serious
      secondary causes of headache, such as tumor, subdural hematoma, stroke, transient
      ischemic attack, and temporal arteritis. When older patients present with
      headache, a lowered threshold for ordering tests is justified, particularly if
      the headaches are of recent onset, are atypical, or are associated with
      neurologic findings. This article discusses the secondary causes of headache in
      the elderly and the symptoms and appropriate testing and treatment of these
      headaches. The epidemiology and treatment of the primary headache disorders in
      the elderly are reviewed. 

PMID- 24572383
TI  - Integrated EMG study of the medial and lateral heads of the gastrocnemius during
      isometric plantar flexion with varying cuff weight loads.
AB  - Both heads of the gastrocnemius muscle contribute to ankle plantar flexion. This
      study utilized integrated electromyography to investigate whether the percent
      electrical activity contributed by each head remained constant or changed during
      isometric contractions at five different resistance levels. Fifty healthy
      volunteers ranging in age from 19 to 34 years, with no history of musculoskeletal
      or neuromuscular disorders involving the right lower extremity, were studied. All
      tasks were performed in the prone position, knee in extension, with the leg and
      foot in neutral with respect to rotation. Motor points of the medial head and
      lateral head were identified and surface electrodes were placed just distal to
      them. The subjects maintained 20 degrees  of plantar flexion under five
      conditions: a maximal isometric plantar flexion contraction (one trial only), and
      with a 5-, 10-, 15- and 20-lb cuff weight attached to the right foot (three
      trials each). EMG recordings, 8 s in length, were taken during the isometric
      contractions. Integrated EMGs were averaged for each cuff weight and the
      resulting values used in the analysis. A repeated measures ANOVA was performed
      and a significance level of p<=0.05 was used to determine statistical
      significance. As weight increased, the absolute value of the integrated EMG
      recorded over both muscles increased, but the percent contributed by each head
      remained essentially equal (50%) within the four submaximal loads tested.
      However, for the maximal isometric contraction, the medial head contributed a
      significantly higher percentage of the total integrated EMG (58%). Therefore, in
      the open-chain activity described, the two heads of the gastrocnemius demonstrate
      similar neural drive at submaximal levels of contraction, but this changes as
      maximum isometric levels are reached. 

PMID- 24572384
TI  - The use of spinal opioids in cancer pain.
AB  - Approximately two-thirds of cancer patients suffer from significant pain. Until
      recently, less expensive and less costly conservative treatments have been
      utilized to treat these patients' pain, but the outcomes have been poor, with
      many experiencing inadequate pain relief. Although intraspinal opioid therapy is
      relatively new and more invasive than traditional treatments, it can provide most
      cancer patients better pain relief with less side effects. Intraspinal opioids
      can be used successfully to treat intractable malignant pain states. 

PMID- 24572385
TI  - The Impact Of Florida's Low-Back Practice Guideline on Treatment of New Workers'
      Compensation Injuries.
AB  - SUMMARY: Low-back injuries are among the most common and costly work-related
      injuries. Many studies show a wide variation in the diagnostic and therapeutic
      approaches to treat these injuries. To help standardize medical practice patterns
      and reduce the use of procedures with little or no proven benefit, the Agency for
      Health Care Administration (AHCA) developed and endorsed a scientifically sound
      medical practice guideline for the treatment of low-back injuries.This study
      investigates the potential of the guideline to reduce workers' compensation costs
      by reducing unnecessary diagnostic and therapeutic treatments to workers with low
      back injuries. The study considers the universe of new low-back injuries reported
      to the Department of Labor and Employment Security (DLES) during the period
      October 1993 through September 1994. As many as two-thirds of the procedures
      provided to these workers were outside the guideline recommendations. In seven
      out of 11 procedure categories tested, 50% or more of the procedures were outside
      the guideline. In five of these areas, as many as 90% of the procedures were
      outside the guideline. The use of procedures outside the guideline was widespread
      across all major diagnosis groups, carrier types, geographic regions and
      practitioner types. POLICY IMPLICATIONS: These results suggest that a large
      percentage of the procedures in use during the study period were unnecessary.
      Unnecessary procedures represent inessential spending and, in some cases,
      needless patient risk. The Florida low-back guideline has great potential to
      reduce practice variation and standardize treatment patterns according to the
      best scientific evidence.Relevant Florida Statutes: Section 408.02, Florida
      Statutes, authorizes AHCA to develop and endorse medical practice guidelines.
      Section 440.13, Florida Statutes, requires workers' compensation insurance
      carriers and DLES to use guidelines in evaluating the appropriateness and
      overutilization of medical services provided to injured employees.For information
      Contact: Russell E. Mardon, Ph.D or Glenn E. Mitchell, Ph.D., Co-Principal
      Investigators, State Center for Health Statistics Agency for Health Care
      Administration. + 1 850 9225866, + 1 850 9225569.

PMID- 24572387
TI  - Anatomical workshops in orthopaedic surgery 1998/99.

PMID- 24572388
TI  - Scientist-versus-activist debates mislead the public.

PMID- 24572400
TI  - Vietnam on high alert over flu risk.

PMID- 24572401
TI  - Monkey brains wired to share.

PMID- 24572402
TI  - Sao Paulo poised to join megatelescope.

PMID- 24572403
TI  - Einstein's lost theory uncovered.

PMID- 24572404
TI  - Fish-kill method questioned.

PMID- 24572405
TI  - SOFIA irons out technical kinks.

PMID- 24572407
TI  - Crowd-sourcing: Strength in numbers.

PMID- 24572412
TI  - Q&A: Melodic psychologist. Interview by Jascha Hoffman.

PMID- 24572408
TI  - Science in court: Disease detectives.

PMID- 24572413
TI  - Developing world: Global fund needed for STEM education.

PMID- 24572414
TI  - Stamina therapies: Let the record stand.

PMID- 24572415
TI  - University budgets: Expand fundraising by Brazil's institutes.

PMID- 24572416
TI  - Stamina therapies: Time to call a halt.

PMID- 24572417
TI  - Tuberculosis: Drug discovery goes au naturel.

PMID- 24572418
TI  - Applied physics: Optical trapping for space mirrors.
AB  - Might it be possible to create mirrors for space telescopes, using nothing but
      microscopic particles held in place by light? A study that exploits a technique
      called optical binding provides a step towards this goal.

PMID- 24572421
TI  - Atmospheric science: Involatile particles from rapid oxidation.

PMID- 24572422
TI  - Quantum droplets of electrons and holes.
AB  - Interacting many-body systems are characterized by stable configurations of
      objects--ranging from elementary particles to cosmological formations--that also
      act as building blocks for more complicated structures. It is often possible to
      incorporate interactions in theoretical treatments of crystalline solids by
      introducing suitable quasiparticles that have an effective mass, spin or charge
      which in turn affects the material's conductivity, optical response or phase
      transitions. Additional quasiparticle interactions may also create strongly
      correlated configurations yielding new macroscopic phenomena, such as the
      emergence of a Mott insulator, superconductivity or the pseudogap phase of high
      temperature superconductors. In semiconductors, a conduction-band electron
      attracts a valence-band hole (electronic vacancy) to create a bound pair, known
      as an exciton, which is yet another quasiparticle. Two excitons may also bind
      together to give molecules, often referred to as biexcitons, and even
      polyexcitons may exist. In indirect-gap semiconductors such as germanium or
      silicon, a thermodynamic phase transition may produce electron-hole droplets
      whose diameter can approach the micrometre range. In direct-gap semiconductors
      such as gallium arsenide, the exciton lifetime is too short for such a
      thermodynamic process. Instead, different quasiparticle configurations are
      stabilized dominantly by many-body interactions, not by thermalization. The
      resulting non-equilibrium quantum kinetics is so complicated that stable
      aggregates containing three or more Coulomb-correlated electron-hole pairs remain
      mostly unexplored. Here we study such complex aggregates and identify a new
      stable configuration of charged particles that we call a quantum droplet. This
      configuration exists in a plasma and exhibits quantization owing to its small
      size. It is charge neutral and contains a small number of particles with a pair
      correlation function that is characteristic of a liquid. We present experimental
      and theoretical evidence for the existence of quantum droplets in an electron
      hole plasma created in a gallium arsenide quantum well by ultrashort optical
      pulses.

PMID- 24572426
TI  - Retraction: The NAD-dependent deacetylase SIRT2 is required for programmed
      necrosis.

PMID- 24572423
TI  - A large source of low-volatility secondary organic aerosol.
AB  - Forests emit large quantities of volatile organic compounds (VOCs) to the
      atmosphere. Their condensable oxidation products can form secondary organic
      aerosol, a significant and ubiquitous component of atmospheric aerosol, which is
      known to affect the Earth's radiation balance by scattering solar radiation and
      by acting as cloud condensation nuclei. The quantitative assessment of such
      climate effects remains hampered by a number of factors, including an incomplete
      understanding of how biogenic VOCs contribute to the formation of atmospheric
      secondary organic aerosol. The growth of newly formed particles from sizes of
      less than three nanometres up to the sizes of cloud condensation nuclei (about
      one hundred nanometres) in many continental ecosystems requires abundant,
      essentially non-volatile organic vapours, but the sources and compositions of
      such vapours remain unknown. Here we investigate the oxidation of VOCs, in
      particular the terpene alpha-pinene, under atmospherically relevant conditions in
      chamber experiments. We find that a direct pathway leads from several biogenic
      VOCs, such as monoterpenes, to the formation of large amounts of extremely low
      volatility vapours. These vapours form at significant mass yield in the gas phase
      and condense irreversibly onto aerosol surfaces to produce secondary organic
      aerosol, helping to explain the discrepancy between the observed atmospheric
      burden of secondary organic aerosol and that reported by many model studies. We
      further demonstrate how these low-volatility vapours can enhance, or even
      dominate, the formation and growth of aerosol particles over forested regions,
      providing a missing link between biogenic VOCs and their conversion to aerosol
      particles. Our findings could help to improve assessments of biosphere-aerosol
      climate feedback mechanisms, and the air quality and climate effects of biogenic
      emissions generally. 

PMID- 24572428
TI  - Is SIRT2 required for necroptosis?
AB  - Sirtuins can promote deacetylation of a wide range of substrates in diverse
      cellular compartments and regulate many cellular processes1,2. Recently Narayan
      et al., reported that SIRT2 was required for necroptosis based on their findings
      that SIRT2 inhibition, knock-down or knock-out prevented necroptosis. We sought
      to confirm and explore the role of SIRT2 in necroptosis and tested four different
      sources of the SIRT2 inhibitor AGK2, three independent siRNAs against SIRT2, and
      cells from two independently generated Sirt2-/- mouse strains, however we were
      unable to show that inhibiting or depleting SIRT2 protected cells from
      necroptosis. Furthermore, Sirt2-/- mice succumbed to TNF induced Systemic
      Inflammatory Response Syndrome (SIRS) more rapidly than wild type mice while
      Ripk3-/- mice were resistant. Our results therefore question the importance of
      SIRT2 in the necroptosis cell death pathway.

PMID- 24572429
TI  - Outcome of adjuvant therapy in biliary tract cancers.
AB  - OBJECTIVE: There are high rates of recurrence after definitive surgery in biliary
      tract cancer patients. We reviewed the use and effectiveness of adjuvant therapy
      (AT; chemotherapy+/-radiotherapy) in a single institution series. METHODS:
      Characteristics, treatment details, and follow-up data of all patients with
      biliary tract cancer who had definitive surgery from January 1987 to September
      2011 were reviewed. The association between baseline variables and disease-free
      survival/overall survival (OS) were tested using Cox proportional hazard analysis
      in the univariable and multivariable settings. RESULTS: Analysis included 296
      patients (58% male; median age, 63 y). Negative or microscopically positive
      resections were reported in 42% and 14%, respectively, with 44% not reported.
      Node positivity was reported in 35% patients. AT was given in 28% of patients
      with 59% receiving chemotherapy and 35% concurrent chemotherapy/radiotherapy.
      Disease recurred in 60% patients. AT was associated with significantly improved
      OS (hazard ratio, 0.41; P=0.02). Compared with R0 resection, patients with R1
      resection derived significantly increased benefit from AT (P for difference
      0.02). In the node positive population (n=103), AT was associated with
      significantly improved OS (hazard ratio, 0.60; 95% confidence interval, 0.38
      0.95; P=0.03). CONCLUSIONS: Patients with R1 resection and node positive disease
      receiving AT after definitive surgery seem to derive OS advantage. Large
      prospective trials are needed to confirm these data.

PMID- 24572430
TI  - Antihypertensive drugs methyldopa, labetalol, hydralazine, and clonidine improve
      trophoblast interaction with endothelial cellular networks in vitro.
AB  - OBJECTIVES: The interaction between trophoblasts and maternal endothelium is
      important for placental vascular modeling. Failure of uterine spiral artery
      transformation is linked to the etiopathology of preeclampsia. Antihypertensive
      medications used to control hypertension in early pregnancy can alter placental
      and circulating cytokines. This study investigated whether selected
      antihypertensive drugs can modulate the interaction between trophoblast and
      endothelial cells. METHODS: Human uterine myometrial microvascular endothelial
      cells were preincubated with (or without) low-dose tumor necrosis factor-alpha
      (TNF-alpha; 0.5 ng/ml) or TNF-alpha and soluble fms-like tyrosine kinase 1 (sFlt
      1; 100 ng/ml). Red fluorescent-labeled endothelial cells were then cultured on
      Matrigel. After appearance of endothelial cellular networks, green fluorescent
      labeled HTR-8/SVneo trophoblast cells were cocultured in the presence of
      pharmacological doses of methyldopa, labetalol, hydralazine, and clonidine.
      Images were captured after 24 h and drug effects on HTR-8/SVneo cell integration
      were quantified by Image Analysis software. The conditioned medium was collected
      to measure sFlt-1, vascular endothelial growth factor (VEGF), placental growth
      factor, interleukin-10, and interleukin-6 by ELISA. RESULTS: Methyldopa,
      labetalol, hydralazine, and clonidine increased trophoblast integration into TNF
      alpha-preincubated endothelial cellular networks. In conditioned medium, sFlt-1
      was reduced by methyldopa, hydralazine, and clonidine alone. VEGF was increased
      by methyldopa. A decrease in placental growth factor was seen by methyldopa and
      also in nontreated endothelial cell coculture of the other three drugs.
      CONCLUSION: Some antihypertensive drugs used in pregnancy may improve the
      cellular interaction between trophoblast and endothelial cells exposed to TNF
      alpha. Methyldopa, hydralazine, and clonidine reduced sFlt-1 concentration in
      culture medium, whereas labetalol increased trophoblast integration independently
      of sFlt-1. Methyldopa increased VEGF concentration. Some pregnancy-related
      antihypertensives may affect placental vascularization.

PMID- 24572431
TI  - Night-time heart rate cut-off point definition by resting office tachycardia in
      untreated hypertensive patients: data of the Spanish ABPM registry.
AB  - OBJECTIVE: Epidemiological studies have shown that an elevated resting heart rate
      (HR) is a risk factor for both total and cardiovascular mortality. Our aim was to
      estimate the night-time HR cut-off point that best predicts cardiovascular risk
      office tachycardia in hypertensive patients. DESIGN AND METHOD: Untreated
      hypertensive patients without concomitant cardiovascular diseases were included.
      Office and ambulatory HRs were measured. Cardiovascular risk office tachycardia
      was defined by office HR at least 85 beats per minute (bpm). Different night-time
      HR cut-offs were estimated by receiver operating characteristic curve analyses to
      predict cardiovascular risk office tachycardia. The best cut-off was selected on
      the basis of its combined sensitivity and specificity. RESULTS: A total of 32 569
      hypertensive patients were included: 46.5% women, mean age (SD) 52 (14) years,
      office blood pressure 146 (16)/89 (11) mmHg, diabetes 10.3%, smoking 19.2%, BMI
      29 (6.8) kg/m, office HR 77 (11.2) bpm, and night-time HR 64.9 (9.3) bpm. A total
      of 7070 (21.7%) patients were found to have cardiovascular risk office
      tachycardia. The night-time HR value that better predicted cardiovascular risk
      office tachycardia was more than 66 bpm. In comparison with patients with night
      HR below this value, those with night-time tachycardia were predominantly women,
      younger, with higher ambulatory blood pressure, greater BMI, and higher
      prevalence of diabetes and smoking. All comparisons were statistically
      significant (P less than 0.001). CONCLUSION: A mean night-time HR more than 66
      bpm is a good predictor of cardiovascular risk office tachycardia in untreated
      hypertensive patients and could be considered a variable associated with an
      increased cardiovascular risk.

PMID- 24572432
TI  - Surgical management of paediatric chronic rhinosinusitis: review of 10 years'
      experience.
AB  - OBJECTIVE: To assess the outcome of children with chronic rhinosinusitis who were
      managed surgically, over a 10-year study period. METHOD: From January 1999 to
      December 2008 inclusive, 136 children diagnosed with chronic rhinosinusitis
      underwent surgery following unsuccessful medical treatment. The operations ranged
      from adenoidectomy to functional endoscopic sinus surgery. RESULTS: The surgical
      procedures performed were: adenoidectomy (n=69), antral washouts (n=54), middle
      meatal antrostomy (n=82), endoscopic ethmoidectomy (n=66), nasal septal
      reconstruction (n=10), and inferior turbinate outfracture (n=23) or inferior
      turbinate reductions (n=55). Follow-up duration ranged from 6 months to 9 years
      (average 3.2 years). Three patients required revision surgery: adenoidectomy in
      two patients and adenoidectomy with turbinate reductions in another. CONCLUSION:
      This study demonstrates the benefits of focused surgical treatment for paediatric
      chronic rhinosinusitis. Surgical treatment can be an appropriate and effective
      option for children with chronic rhinosinusitis when medical management is
      unsuccessful.

PMID- 24572433
TI  - Assessment of recurrent mesenteric ischemia after stenting with a pressure wire.
AB  - Chronic mesenteric artery ischemia can be difficult to evaluate after stent
      placement. This case describes the use of a pressure wire to demonstrate the
      hemodynamic significance of in-stent restenosis. Papaverine was used to
      vasodilate the mesenteric bed, mimicking the post-prandial state. The study
      (arteriography with pressure wire) and retreatment (covered balloon-expandable
      stent) was driven by recurrent symptoms avoiding unnecessary ancillary testing.

PMID- 24572434
TI  - From the editor.

PMID- 24572435
TI  - Cervical strain/sprain (is this a metaphor or a medical diagnosis?).

PMID- 24572436
TI  - Recent advances in orofacial pain and temporomandibular disorders.
AB  - The field of orofacial pain and temporomandibular disorders (OFP/TMD) is a
      relatively new area of clinical and scientific interest that parallels the
      expanding interest in pain conditions in the back and other areas of the body.
      This new field is concerned with the understanding and care of patients with
      disorders that cause pain and dysfunction of the masticatory system and related
      orofacial, head, and neck structures. Because orofacial structures are integrally
      involved in communication, sustenance, sexuality, appearance, and self esteem,
      the personal impact of these disorders can be high, motivating patients to seek
      care and be a significant part of the clinical practice of dentistry and
      medicine. As a result of recent developments in research, education, and patient
      care in the past 10 years, significant progress has been made in helping patients
      with these disorders. These efforts can provide an example of what can be done
      with other pain disorders to advance efforts in research, teaching, and patient
      care. The purpose of this paper is to review these recent advances in OFP/TMD and
      their implications for patient care. 

PMID- 24572437
TI  - Orofacial pain - an overview.
AB  - Orofacial pain is a complex problem that requires careful assessment,
      understanding and appropriate therapy. This article reviews the function of the
      nervous system as it pertains to orofacial pain and introduces an organ based
      classification system that can be used to help differentiate the patient with
      orofacial pain. Current concepts in the pathogenous of each disorder and
      therapies are reviewed. 

PMID- 24572438
TI  - Orthopedic diagnostic tests for temporomandibular and cervical spine disorders.
AB  - The interexaminer reliability of six orthopedic tests, applied to the masticatory
      system, was determined in a group of 79 patients with signs and/or symptoms of
      TMD. Multitest Scores were composed for each test and combinations of tests for
      the three main symptoms of TMD, namely, pain, joint sounds, and restriction of
      movement. Although the tests showed different reliability scores, the reliability
      of detecting these three main symptoms of TMD was satisfactory. All the tests
      contributed to the diagnostic process, with active movements being the most
      powerful test. The combination of active movements, passive movements, and
      palpation provided valuable diagnostic information. Other tests could be used for
      specific diagnostic problems. The scores of the orthopedic tests applied to the
      neck show that extension and flexion can be evaluated most reliably with active
      movements and by assessing end feel. The interexaminer agreement for recording
      pain was also satisfactory for flexion and extension. The interexaminer
      reliability of the tests recording pain and end feel in the shoulder girdle was
      moderate for anteflexion. 

PMID- 24572439
TI  - Systemic ligament hypermobility in temporomandibular disorders.
AB  - Systemic ligament hypermobility (benign hypermobile joint syndrome or BHJS) and
      masticatory parafunction (clenching/bruxism) were evaluated in intracapsular TMD
      (n=110) and non-TMD (n=112) populations. Individuals that had a ligament mobility
      index greater than four were classified as benign hypermobile joint syndrome
      (BHJS) utilizing the modified Carter-Wilkinson systemic ligament hypermobility
      scale. All subjects in the TMD and control groups were female, between the ages
      of 10 and 79 with Angles' Class I molars and cuspids. This study found Benign
      Hypermobile Joint Syndrome (BHJS) and masticatory parafunction, when present
      simultaneously in females, to be significantly associated with intracapsular TMD
      symptoms (P<0.001). 

PMID- 24572440
TI  - Bruxism: A factor associated with temporomandibular disorders and orofacial pain.
AB  - Rhythmic masticatory muscle activities are probably part of normal jaw motor
      behavior. Certain factors, like disease, stress, personality, alcohol, and
      medication, may turn this normal activity into a condition that might include
      abnormal tooth wear, myofascial pain, and temporomandibular joint problems. This
      condition then corresponds with bruxism. Bruxism and masticatory muscle pain may
      reciprocally influence one another: although not a compulsory finding, bruxism
      may be associated with the predisposition, initiation, and perpetuation of
      temporomandibular disorders and orofacial pain. On the other hand, the presence
      of jaw muscle pain may reduce bruxism motor activity. Research on the integrity
      and nature of the relationship between bruxism and pain is hampered by
      controversies that exist regarding definition, diagnostic criteria, and
      measurement techniques. Moreover, the pathophysiology of bruxism and its
      association with other sleep-related and movement disorders are still unclear.
      Consequently, there is no real cure for bruxism, although several treatments may
      be used to control its adverse effects. However, there is very limited research
      to support the efficacy of behavioral, physical, dental, pharmacological, and
      orthopedic treatments. Probably the best current treatment modality for bruxism
      is the occlusal stabilization splint. Although such an orthopedic device may not
      actually prevent bruxism, it may help to reduce its symptoms. 

PMID- 24572441
TI  - Myofascial pain of the head and neck: diagnosis and management.
AB  - Myofascial pain (MFP) is a regional muscle pain disorder characterized by
      localized muscle tenderness and pain and the most common causes of persistent
      pain in the head and neck. The affected muscles may also display an increased
      fatigability, stiffness, subjective weakness, pain in movement, and slight
      restricted range of motion that is unrelated to joint restriction. MFP is
      frequently overlooked as a diagnosis because it is often accompanied by signs and
      symptoms in addition to pain, coincidental pathology conditions such as joint
      disorders, and behavioral and psychosocial problems. As MFP persists, chronic
      pain characteristics often precede or follow its development. Evaluation of
      myofascial pain includes locating the trigger points and muscles involved as well
      as recognition of these contributing factors. Management of the syndrome
      naturally follows with muscle exercises, therapy to the trigger points, and
      reducing all contributing factors. The difficulty in managing MFP lies in the
      critical need to match the level of complexity of the management program with the
      complexity of the patient. 

PMID- 24572442
TI  - The role of surgery in the management of chronic temporomandibular joint pain.
AB  - Although most painful conditions affecting the temporomandibular joint (TMJ) can
      be managed non-surgically, when such treatment fails, surgery is often
      recommended as an alternative. The success of surgery depends on accurate
      diagnosis, an understanding of which conditions are amenable to operation, and
      knowing what to do and when to do it. This article provides the information
      needed by the clinician to determine when surgery should be done for chronic TMJ
      pain and what can be accomplished by such treatment. 

PMID- 24572443
TI  - Erratum to "An easy way to quantify plantarflexion in the ankle" [J. Back
      Musculoskelet. Rehabil. 5 (1995) 191-199].

PMID- 24572446
TI  - Manual medicine - state of the art 1996.

PMID- 24572444
TI  - Contents of journals relating to back and musculoskeletal rehabilitation.

PMID- 24572447
TI  - Development of a respiratory sensitization/elicitation protocol of toluene
      diisocyanate (TDI) in Brown Norway rats to derive an elicitation-based
      occupational exposure level.
AB  - Toluene diisocyanate (TDI), a known human asthmagen, was investigated in skin
      sensitized Brown Norway rats for its concentration*time (C*t)-response
      relationship on elicitation-based endpoints. The major goal of study was to
      determine the elicitation inhalation threshold dose in sensitized, re-challenged
      Brown Norway rats, including the associated variables affecting the dosimetry of
      inhaled TDI-vapor in rats and as to how these differences can be translated to
      humans. Attempts were made to duplicate at least some traits of human asthma by
      using skin-sensitized rats which were subjected to single or multiple inhalation
      escalation challenge exposures. Two types of dose-escalation protocols were used
      to determine the elicitation-threshold C*t; one used a variable C (Cvar) and
      constant t (tconst), the other a constant C (Cconst) and variable t (tvar). The
      selection of the "minimal irritant" C was based an ancillary pre-studies.
      Neutrophilic granulocytes (PMNs) in bronchoalveolar lavage fluid (BAL) were
      considered as the endpoint of choice to integrate the allergic pulmonary
      inflammation. These were supplemented by physiological measurements
      characterizing nocturnal asthma-like responses and increased nitric oxide in
      exhaled breath (eNO). The Cconst*tvar regimen yielded the most conclusive dose
      response relationship as long C was high enough to overcome the scrubbing
      capacity of the upper airways. Based on ancillary pre-studies in naive rats, the
      related human-equivalent respiratory tract irritant threshold concentration was
      estimated to be 0.09ppm. The respective 8-h time-adjusted asthma-related human
      equivalent threshold C*t-product (dose), in 'asthmatic' rats, was estimated to be
      0.003ppm. Both thresholds are in agreement of the current ACGIH TLV((r)) of TDI
      and published human evidence. In summary, the findings from this animal model
      suggest that TDI-induced respiratory allergy is likely to be contingent on two
      interlinked, sequentially occurring mechanisms: first, dermal sensitizing
      encounters high enough to cause systemic sensitization. Second, when followed by
      inhalation exposure(s) high enough to initiate and amplify an allergic airway
      inflammation, then a progression into asthma may occur. This bioassay requires an
      in-depth knowledge on respiratory tract dosimetry and irritation of the involved
      test substance to clearly understand the dosimetry causing C- and/or C*t
      dependent respiratory tract irritation and eventually asthma.

PMID- 24572448
TI  - Helicobacter pylori infection and respiratory diseases: actual data and
      directions for future studies.
AB  - Helicobacter pylori (H. pylori) has been conclusively related to several
      gastroduodenal diseases. The possible role of the bacterium in the development of
      extragastric manifestations has been investigated in the past few years. To
      identify all publications on the association between H. pylori and respiratory
      diseases, a MEDLINE search of all studies published in English from 1965 to 2013
      was conducted. All data are based on case-control studies. Controversial findings
      of H. pylori seroprevalence have been obtained in patients with bronchial asthma,
      lung cancer, pulmonary tuberculosis, sarcoidosis, cystic fibrosis, chronic
      bronchitis and bronchiectasis. At present, on epidemiological bases, there is no
      definite evidence of a causal relationship between H. pylori infection and
      respiratory diseases. There is a low consideration of confounding factors as
      poorer socioeconomic status and tobacco use. The activation of pro-inflammatory
      cytokines by H. pylori might be a possible pathogenetic mechanism. However, there
      are no convincing data about the influence of H. pylori on the inflammatory
      changes of the bronchoepithelium so far. Further studies are needed on the impact
      of H. pylori eradication, on the prevention, development and natural history of
      these disorders. 

PMID- 24572449
TI  - The role of the inflammasome in fibrotic respiratory diseases.
AB  - Fibrotic respiratory diseases severely disrupt lung function and currently have
      an extremely poor prognosis. This is attributable to the limited amount of
      treatment options available, in part due to our lack of understanding of the
      mechanisms driving disease pathogenesis. Although the majority of cases appear to
      be idiopathic, a number of factors are known to cause pulmonary fibrosis, such as
      the inhalation of silica crystals (silicosis), asbestos fibers (asbestosis) and
      certain drugs such as bleomycin. Evidence suggests that the inhalation of such
      substances can induce the formation of the NLRP3 inflammasome; a multimeric
      protein complex responsible for the activation of caspase-1 and maturation of the
      proinflammatory cytokines IL-1b and IL-18. Moreover, data suggests that
      inhibition of the inflammasome activation pathway and/or inflammasome-mediated
      cytokines can attenuate the fibrotic response in in vitro and in vivo models of
      disease. In this review, we discuss the evidence suggesting that the NLRP3
      inflammasome plays an important role in the pathogenesis of fibrotic respiratory
      diseases, and the potential mechanisms by which activation of the NLRP3
      inflammasome may occur. It is possible that fibrotic respiratory diseases with a
      known cause may share a common mechanism with idiopathic pulmonary fibrosis,
      providing possible strategies for future drug therapies. 

PMID- 24572450
TI  - The upper airway in sleep-disordered breathing: UA in SDB.
AB  - Sleep disordered breathing (SDB) is a common condition and could be a risk factor
      for cardiovascular morbidity and mortality. However, the pathogenesis of SDB
      remains to be elucidated. In general, SDB is divided into two forms, obstructive
      and central sleep apnea (OSA and CSA, respectively). OSA results from the sleep
      related collapse of the upper airway (UA) in association with multiple factors
      like race, gender, obesity and UA dimensions. CSA primarily results from a fall
      in PaCO2 to a level below the apnea threshold during sleep through the reflex
      inhibition of central respiratory drive. It has been reported that UA alterations
      (i.e., collapse or dilation) can be observed in CSA. This review highlights the
      roles of the UA in the pathogenesis and pathophysiology of SDB. 

PMID- 24572451
TI  - Robuvit(r) (French oak wood extract) in the management of functional, temporary
      hepatic damage. A registry, pilot study.
AB  - AIM: The aim of this registry study was to evaluate the evolution of moderate
      functional hepatic failure (MTHF) using a proprietary new oak wood supplement
      (Robuvit(r)) extracted from Quercus Robur. Recent studies have indicated the
      protective effect of oak wood extracts on liver injury. Quercus wood extracts
      have shown hepatoprotective effect on initial induced liver-injury. METHODS: This
      registry included a total of 75 patients with MTHF characterized by: decreased
      albumin levels; increased total bilirubin, altered hepatic functions enzymes,
      increased oxidative stress, negative viral hepatitis markers. RESULTS: The two
      groups (best management in comparison with best management+ Robuvit(r)) were
      comparable: 32 Robuvit(r) patients and 29 comparable controls) completed the 12
      week registry. At inclusion, the blood parameter values in the two groups were
      comparable. At the end of the supplementation period, the increase in albumin
      levels was significantly (P<0.05 at 12 weeks) faster and higher in the Robuvit(r)
      group. The decrease in ALT-SGPT and AST-ASAT was significant in the supplement
      group (P<0.05 at 4 and 12 weeks); the tests were normalized at 4 and 12 weeks.
      Controls remained out of the normal range for more than 12 weeks. Alkaline
      phosphatase was normalized at 4 and 12 weeks in Robuvit(r) patients; they were
      decreased, but not normalized in controls at 4 weeks (Robuvit(r) group's values
      were significantly better; P<0.05). Values were normalized in controls
      (significantly higher in comparison with Robuvit(r); P<0.05) at 12 weeks. Total
      bilirubin was normalized in Robuvit(r) subjects at 4 and 12 weeks. Results were
      significantly better in comparison with controls (P<0.05). Direct bilirubin
      values increased more in the Robuvit(r) group at 4 and 12 weeks (P<0.05). Gamma
      GT values were normalized at 4 and 12 weeks in the Robuvit(r) group. There was a
      less important decrease in controls (P<0.05) without normalization at 12 weeks.
      Plasma free radicals increased at inclusion showed a significant decrease in
      Robuvit(r) subject (at 4 and 12 weeks) with normalization at 12 weeks.
      Persisting, elevated values in controls were observed even at 12 weeks (P<0.05).
      ESR and CRP decreased in both groups with a more important decrease in the
      Robuvit(r) group (P<0.05). Hepatitis markers were negative when repeated at 4 and
      12 weeks. CONCLUSION: Data from this pilot, supplement registry study indicate a
      significant protective activity of Robuvit(r), associated with a very good safety
      profile, in patients with temporary hepatic failure. The activity of Robuvit(r)
      seems to be mediated by its anti-inflammatory activity.

PMID- 24572452
TI  - Insulin resistance via modification of PGC1alpha function identifying a possible
      preventive role of vitamin D analogues in chronic inflammatory state of obesity.
      A double blind clinical trial study.
AB  - AIM: Obesity-induced chronic inflammation is a key component of the pathogenesis
      of insulin resistance. Mounting evidence has demonstrated anti-inflammatory
      characteristics for vitamin D. Although analogues of vitamin D3 have extensively
      been used in the treatment of various chronic inflammatory diseases, to our
      knowledge, no such research is conducted in regards with obesity. The aim of this
      double blind clinical trial study is to investigate whether alphacalcidol
      treatment in obese subjects can affect the cytokine profile and insulin
      resistance. Moreover, we evaluated the pathways of vitamin D receptor (VDR),
      PPARgamma and PGC1alpha gene expressions which may lead to insulin resistance
      following treatment with either alphacalcidol or placebo. METHODS: A total of 94
      obese participants (BMI>=30) were recruited for the current double blind clinical
      trial study. Patients were divided into two intervention (N.=40) and control
      groups (N.=54) based on the stratified randomized method. One-Alpha(r) Capsules 1
      microgram: alfacalcidol (1-alpha hydroxyvitamin D3) and placebo were given to
      subjects once a day for 8 weeks. Analysis of body composition was performed with
      use of Body Composition Analyzer. The circulating levels of TNF-alpha, IL-1beta,
      IL-4, IL-6, IL-10, IL-13, IL-17, PTH, and 25-Hydroxy Vi-tamin D were measured
      with the use of EIA method. The PBMCs were separated from whole blood by Ficoll
      hypaque technique. Total cellular RNA was extracted and the cDNA was synthesized.
      The real-time PCR using specific primer pairs for VDR, PGC1alpha, PPARgamma, and
      beta-actin was performed. RESULTS: The FPG, fat percent and PTH levels were
      decreased and the levels of HDL-cholesterol and 25-hydroxy vitamin D were
      significantly increased after treatment with Alfacalcidol. Regarding to cytokines
      levels, the levels of IL6 were significantly decreased and IL10 were
      significantly increased in Alfacalcidol group in comparison with the control
      group. The relative expressions of VDR, PGC1alpha, and PPARgamma genes
      significantly increased in Alfacalcidol group. We found also significant positive
      correlation between circulating 25-OH vitamin D and relative PGC1alpha gene
      expression in participants with insulin resistance. CONCLUSION: It seems that
      Alfacalcidol treatment may be effective in amelioration of the inflammatory state
      in obesity. This supplement might also improve resistance to insulin through
      enhancement of relative VDR and its downstream genes expression, which are
      demonstrated to be involved in glucose homeostasis pathways.

PMID- 24572453
TI  - Influence of single hemodialysis session on serum paraoxonase-1, arylesterase
      activity, total oxidant status and total antioxidant status.
AB  - AIM: Chronic kidney disease(CKD) and hemodialysis (HD) are associated with
      increased oxidative stress. Cardiovascular diseases (CVD) are the most important
      cause of mortality in these patients. Increased cardiovascular risk is associated
      with oxidative stress. The aim of this study was to evaluate whether the duration
      of single session hemodialysis may affect oxidative stress parameters on the
      patients with end-stage renal disease (ESRD). METHODS: Total oxidant status (TOS)
      and oxidative stress index (OSI) as oxidative markers and total antioxidant
      status (TAOS), paraoxonase1 (PON1) and arylesterase (ARES) as antioxidant markers
      were compared hemodialysis therapy before and after the treatment. RESULTS: TOS
      levels before hemodialysis were found as 4.4+/-2.4 MUmol H2O2 Equiv/L, TAOS 2.1+/
      0.3 umol trolox Equiv./L, OSI 0.2+/-0.1%, PON1 levels 58.5+/-35.6 U/L and ARES
      levels 22+/-0.2 U/L while after the HD the respective values were 1.4+/-1.2 MUmol
      H2O2 Equiv/L, 1.4+/-0.5 umol trolox Equiv./L, 0.1+/-0.1%, 54.3+/-31.3 U/L, 21.8+/
      0.1 U/L. A significant decreasing was observed in TOS TAOS OSI and ARES values
      before the HD compared to after the HD (P=0.0001, P=0.0001, P=0.0001, P=0.031,
      respectively). CONCLUSION: This study shows oxidant (TOS, OSI) and antioxidant
      (TAOS, ARES) markers were found to be significantly decrease after the HD
      compared to pre-hemodialysis. Although reverse is expected it is found that
      oxidants (indirectly ROS) did not increase and antioxidant reserve decreased in
      HD.

PMID- 24572454
TI  - Pneumococcal vaccination strategies in adult population: perspectives with the
      pneumococcal 13 - valent polysaccharide conjugate vaccine.
AB  - Streptococcus pneumoniae (Sp) is a leading cause of infection in people of all
      ages worldwide, determining a significant impact because of its relatively high
      incidence rate, the associated economic costs, and the high case-fatality rates.
      More attention has to be paid for elderly and people with one or more risk
      factors, in order to reduce health costs and pneumococcal hospital admissions.
      Moreover, the increasing incidence of antibiotic-resistant Sp strains is a source
      of concern for its relevant clinical importance in health-care settings. At
      present, the 23-valent polysaccharide (PPV23) vaccine has shown some limits in
      terms of protection in the elderly population and against invasive diseases,
      among adults affected with chronic diseases, non-bacteriemic pneumonias and with
      immune suppression, in particular in adults with HIV. In December 2011, FDA
      licensed the 13-valent pneumococcal conjugate vaccine (PCV13) for prevention of
      pneumonia and invasive diseases (IPDs) in adults aged >=50 years. The same
      decision was concomitantly assumed in Europe by EMA. PCV13 has shown superior
      results both in terms of immunogenicity and of adequate stimulation of a stable
      and long-lasting immunological memory. European recommendations for PCV13
      vaccination in adults are still heterogeneous between Countries. The availability
      of PCV13 for adults offer a new and promising tool against Sp IPDs and non-IPDs,
      especially in elderly and at risk populations.

PMID- 24572455
TI  - Nontoxigenic tox-bearing Corynebacterium ulcerans infection among game animals,
      Germany.
AB  - Corynebacterium ulcerans may cause diphtheria in humans and caseous lymphadenitis
      in animals. We isolated nontoxigenic tox-bearing C. ulcerans from 13 game animals
      in Germany. Our results indicate a role for game animals as reservoirs for
      zoonotic C. ulcerans. 

PMID- 24572457
TI  - Sensual sexuality education with young parenting women.
AB  - Comprehensive sexuality education curricula that incorporate sex positive and
      integrated approaches go beyond a presentation of facts and strategies for
      prevention to emphasize the promotion of sexual subjectivity and wellbeing. A
      pilot sensual sexuality education program was planned, implemented and informally
      evaluated with young parenting women at an alternative General Educational
      Development test preparation center. The program prioritized a sex positive
      framework, including topics such as pleasure, desire and sexual entitlement, and
      invited participants to explore sexuality through a multisensory orientation.
      Participants took part in small group discussions and activities that engaged
      their senses through arts-based methods. Grounded in holism, program topics were
      integrated with a focus on participants' everyday experiences. The pilot
      curriculum serves as a promising program for re-positioning young parenting women
      as sexual subjects, which is key to the promotion of health and wellbeing. 

PMID- 24572456
TI  - The role of newborn gender in postpartum depressive symptoms among women in Upper
      Egypt.
AB  - OBJECTIVE: To assess the magnitude of postpartum depression among women in Upper
      Egypt, in addition to the role of newborn gender. METHODS: A cross-sectional
      study was conducted at the outpatient family-planning clinic of a university
      hospital. Women were enrolled if their first offspring was female and if they had
      2 previous deliveries, the last within 3 months; no obstetric complications;
      regular marital life; middle social class or higher; and no past or family
      history of psychiatric illness. The Edinburgh Postnatal Depression Scale (EPDS)
      and Beck Depression Inventory (BDI) were used to assess the prevalence and
      severity of postpartum depressive symptoms. RESULTS: Of the 290 participants, 150
      had a female second child (group 1) and 140 had a male second child (group 2).
      Overall, 113 (39.0%) women scored more than 13 on the EPDS: 70 in group 1 and 43
      in group 2. Of the 113 women, 35 (31.0%) scored mild, 29 (25.7%) scored moderate,
      and 49 (43.4%) scored severe on the BDI. Significantly more women with a female
      second child had severe depression (P<0.001). CONCLUSION: Postpartum depressive
      symptoms were common among the present sample of women in Upper Egypt. Having
      female-only offspring is an important potential risk factor for postpartum
      depression and its severity.

PMID- 24572458
TI  - The effectiveness of HIV/AIDS school-based sexual health education programmes in
      Nigeria: a systematic review.
AB  - HIV/AIDS is one of the most important public health challenges facing Nigeria
      today. Recent evidence has revealed that the adolescent population make up a
      large proportion of the 3.7% reported prevalence rate among Nigerians aged 15-49
      years. School-based sexual health education has therefore become an important
      tool towards fighting this problem. This systematic review assesses the efficacy
      of these educational programmes and examines how future programmes and their
      evaluations can improve. Primary literature published between January 2002 and
      May 2012, which measured sexual health outcomes among school-based Nigerians
      before and after a sexual health education programme was delivered, was
      identified. All seven studies that met the inclusion and exclusion criteria
      showed there had been positive changes in outcomes following these educational
      programmes. These included increased knowledge, healthier attitudes and safer
      sexual health behaviour. However, these studies each had methodological flaws
      which highlighted a range of important design, implementation and evaluation
      challenges that future programmes need to meet. 

PMID- 24572465
TI  - Enhanced vertical carrier mobility in poly(3-alkylthiophene) thin films
      sandwiched between self-assembled monolayers and surface-segregated layers.
AB  - End-functionalized poly(3-butylthiophene) with a thiol group (P3BT-S) was
      synthesized and used to form a self-assembled monolayer (SAM). It can induce the
      end-on orientation in the thin film which has the potential to further enhance
      hole mobility up to 1.1 * 10(-2) cm(2) V(-1) s(-1) in the vertical direction. 

PMID- 24572466
TI  - From the editor.

PMID- 24572467
TI  - Residual functional capacity.

PMID- 24572468
TI  - Functional capacity assessment.

PMID- 24572469
TI  - Process analysis of functional capacity assessment.
AB  - Researchers and practitioners, as well as vendors, have placed much emphasis on
      what constitutes a functional capacity testing battery. Statistical, procedural,
      behavioral, technological, as well as legal issues surrounding this type of human
      performance evaluation are also continuously being addressed in the literature.
      In addition, several methods, batteries, equipment, and protocols have been
      developed for the purpose of evaluating what an injured person can or cannot do.
      It is a fact that 'testing' of individuals is but one component of an intricate
      process consisting of: identification of an evaluee, researching a market,
      referring the evaluee to a facility, evaluating a set of abilities, making
      inference about the evaluee's performance, reporting the findings, following up
      on the case, and possibly a legal involvement due to litigation. These components
      comprise the process of functional capacity testing. The purpose of this paper is
      to describe and analyze the various components of the process of quantitative
      testing of functional capacity. It is believed that each component of the FCA
      process is as important as the actual testing. 

PMID- 24572459
TI  - Analysis of biomolecular interactions using affinity microcolumns: a review.
AB  - Affinity chromatography has become an important tool for characterizing
      biomolecular interactions. The use of affinity microcolumns, which contain
      immobilized binding agents and have volumes in the mid-to-low microliter range,
      has received particular attention in recent years. Potential advantages of
      affinity microcolumns include the many analysis and detection formats that can be
      used with these columns, as well as the need for only small amounts of supports
      and immobilized binding agents. This review examines how affinity microcolumns
      have been used to examine biomolecular interactions. Both capillary-based
      microcolumns and short microcolumns are considered. The use of affinity
      microcolumns with zonal elution and frontal analysis methods are discussed. The
      techniques of peak decay analysis, ultrafast affinity extraction, split-peak
      analysis, and band-broadening studies are also explored. The principles of these
      methods are examined and various applications are provided to illustrate the use
      of these methods with affinity microcolumns. It is shown how these techniques can
      be utilized to provide information on the binding strength and kinetics of an
      interaction, as well as on the number and types of binding sites. It is further
      demonstrated how information on competition or displacement effects can be
      obtained by these methods. 

PMID- 24572470
TI  - Role of functional capacity assessment in disability evaluation.
AB  - Individuals presenting with pain frequently report associated disability. Both
      pain and disability are complex phenomena. The bio-psycho-social complexity of
      pain and the different systems of disability make the evaluation of disability a
      very difficult process. There is a significant mismatch between complaints of
      pain and pathological process, as pathology can be present without symptoms of
      pain. Similarly, the subjective complaints of pain are disassociated with
      objective identification of physical impairment. Finally, the relationship
      between objective impairment determination and its effects on functional
      capacities and disability does not have a one-to-one relationship. Patients with
      pain, especially those with chronic low back pain, have significant impact on
      healthcare costs and on societal costs due to associated disability. Patients,
      employers, legal professionals, and physicians alike, are involved in the
      disability system. Each person is interested in the determination of the
      functional capacities of the individual with pain, so that appropriate return to
      work planning can be initiated. Functional capacities assessment have gained in
      popularity and are frequently accepted by employers and insurance companies alike
      as an objective approach to assess an individual's functional abilities and
      potential limitations. This manuscript provides an overview of the complex nature
      of pain, disability, and the role of functional capacities assessment, as one of
      the many approaches in the medical determination of disability. 

PMID- 24572471
TI  - Standardized evaluation of work capacity.
AB  - A standardized method of evaluation of the work capacity of persons who are
      impaired by soft-tissue injuries is described. A demonstration project which
      involved testing 64 impaired subjects is described. The Cal-FCP test battery can
      be administered independently by a properly trained professional or by a
      technician under a physician's supervision and requires two hours or less to
      complete. This study demonstrated that the results of the test battery are
      unbiased in terms of both gender and age and can be applied to a standardized
      disability rating system. 

PMID- 24572472
TI  - Methods and limitations of assessing functional work capacity objectively.
AB  - This paper examined the methods and issues of assessing objectively the
      functional capacity of workers. The primary emphasis was on aerobic capacity
      (VO2max ) and repetitive lifting. While the direct measurement of expired gases
      during exhausting exercise is the most valid method of assessing the VO2max  of
      workers, it is rarely done outside research or medical settings. The methods more
      commonly used are: maximal exercise tests; submaximal exercise tests; and non
      exercise tests. Maximal tests are accurate, but require medical monitoring when
      testing workers at medical risk. Submaximal tests are less accurate, but are
      safer and faster than a maximal test. Submaximal tests use heart rate response to
      submaximal power output to estimate VO2max ; thus, any factor that alters heart
      rate response reduces the accuracy of the test. Non-exercise tests are as
      accurate as sub maximal tests, but require a self-report rating. The
      physiological criteria used to help define the recommended repetitive lift loads
      of the revised NIOSH equation included baseline aerobic capacity and energy
      expenditure values. While the goal is to reduce the risk of injury, the baseline
      aerobic capacity (~ 25 ml/kg/min) and energy expenditure levels are so low (<=3.5
      METs) that they may have an adverse effect on public health. Normative VO2max 
      data on industrial cohorts suggest that 44% of male and 79% of female industrial
      workers are at a health risk of low aerobic fitness. Data are presented that
      suggests that repetitive lifting tasks are more of a function of strength and fat
      free weight than aerobic capacity. While aerobic capacity, strength, and fat-free
      weight are objective methods to assess functional capacity, worker motivation and
      reaction to chronic pain can affect test results. 

PMID- 24572473
TI  - Functional capacity assessment: Influence of behavioral and environmental
      factors.
AB  - The environment surrounding the functional capacity evaluation (FCA) is complex
      and determined by both external factors as well as those specific to the testing
      situation. In this paper we (1) briefly review existing models of pain, (2)
      highlight how current FCAs of pain patients adhere in general to behavioral
      conceptualizations of chronic pain, (3) review some inadequacies of current
      conceptualizations of FCA when it applies to chronic pain, (4) review the many
      internal and external environmental factors that can significantly influence
      FCAs, and (5) consider some psychosocial factors that play an important role in
      patients' performances. We conclude that not only should evaluators more
      carefully consider the central influences of psychosocial factors when
      interpreting the results of FCAs, but that an alternate conceptual model that
      emphasizes both environmental and psychological factors is also needed to more
      adequately describe the physical performances obtained during FCAs. 

PMID- 24572474
TI  - Validation of sincerity of effort.
AB  - Sincerity of subject effort is critical to the functional capacity assessment
      process. This review examines attempts at devising ways of objectively
      determining whether an evaluee performed his best during functional assessment.
      It is concluded that good, but not conclusive, evidence of submaximal performance
      can be gained in some evaluees. The 5 hand position and the rapid exchange grip
      tests are the best validated and most practical tests devised which can provide
      evidence of malingering. EMG measurements, although not as practical, may be even
      better. Further research is needed to further validate these tests as reliable
      methods of determining sincerity of subject effort. 

PMID- 24572460
TI  - Constraint and opportunity in genome innovation.
AB  - The development of rigorous molecular taxonomy pioneered by Carl Woese has freed
      evolution science to explore numerous cellular activities that lead to genome
      change in evolution. These activities include symbiogenesis, inter- and
      intracellular horizontal DNA transfer, incorporation of DNA from infectious
      agents, and natural genetic engineering, especially the activity of mobile
      elements. This article reviews documented examples of all these processes and
      proposes experiments to extend our understanding of cell-mediated genome change. 

PMID- 24572477
TI  - Author indexVolume 6 (1996).

PMID- 24572476
TI  - Global management of work-related musculoskeletal injuries.

PMID- 24572479
TI  - Volume contentsVolume 6 (1996).

PMID- 24572481
TI  - Downstaging Hepatocellular Carcinoma with Yttrium-90 radioembolization: resection
      or transplantation?
AB  - Trans Arterial Radio Embolization with Yttrium 90 in the treatment of
      Hepatocellular Carcinoma is becoming a new interesting tool in the treatment of
      patients that are considered non resectable and non transplantable. A successful
      downstaging could improve the number of patients that could benefit from a
      resection or a liver transplantation, but some points still need to be addressed.

PMID- 24572480
TI  - Carl Woese's vision of cellular evolution and the domains of life.
AB  - In a series of conceptual articles published around the millennium, Carl Woese
      emphasized that evolution of cells is the central problem of evolutionary
      biology, that the three-domain ribosomal tree of life is an essential framework
      for reconstructing cellular evolution, and that the evolutionary dynamics of
      functionally distinct cellular systems are fundamentally different, with the
      information processing systems "crystallizing" earlier than operational systems.
      The advances of evolutionary genomics over the last decade vindicate major
      aspects of Woese's vision. Despite the observations of pervasive horizontal gene
      transfer among bacteria and archaea, the ribosomal tree of life comes across as a
      central statistical trend in the "forest" of phylogenetic trees of individual
      genes, and hence, an appropriate scaffold for evolutionary reconstruction. The
      evolutionary stability of information processing systems, primarily translation,
      becomes ever more striking with the accumulation of comparative genomic data
      indicating that nearly all of the few universal genes encode translation system
      components. Woese's view on the fundamental distinctions between the three
      domains of cellular life also withstand the test of comparative genomics,
      although his non-acceptance of symbiogenetic scenarios for the origin of
      eukaryotes might not. Above all, Woese's key prediction that understanding
      evolution of microbes will be the core of the new evolutionary biology appears to
      be materializing. 

PMID- 24572482
TI  - Reply to letter: Should videolaryngoscopes be as first choice for endotracheal
      intubation during cardiorespiratory resuscitation?

PMID- 24572483
TI  - Should videolaryngoscopes be as first choice for endotracheal intubation during
      cardiorespiratory resuscitation?: Re: Park SO, et al. Feasibility of the video
      laryngoscope (GlideScope(r)) for endotracheal intubation during uninterrupted
      chest compressions in actual advanced life support: a clinical observational
      study in an urban emergency department. Resuscitation 84 (2013) 1233-1237.

PMID- 24572484
TI  - Stent thrombosis: an increased adverse event after angioplasty following
      resuscitated cardiac arrest.
AB  - BACKGROUND: The leading cause of sudden cardiac death is myocardial ischemia. As
      for uncomplicated acute myocardial infarction (AMI), international guidelines
      plead for early coronary angiography with, in case of culprit lesion, angioplasty
      and stent implantation. However after cardiac arrest (CA), shock, hypothermia and
      changes in antiplatelet pharmacokinetic may promote stent thrombosis (ST).
      Incidence of ST in this situation has never been studied. OBJECTIVE: The aim of
      this study was to investigate incidence and determinants of ST after ischemic CA
      successfully revascularized. METHODS: We analyzed 208 consecutive patients
      admitted in our institution for AMI and who underwent PCI with stent
      implantation. Among these patients, 55 presented a resuscitated CA and were
      compared to 153 without CA (control group). All patients in the CA group received
      hypothermia (33  degrees C for 24 h) following resuscitation and PCI. RESULTS:
      There was no difference between the 2 groups for age, gender, cardiovascular risk
      factors, coronary lesions and type of stent. In the CA group, patients were less
      frequently pre-treated with heparin (50.9% vs 98.7%, p<0.001) and aspirin (52.7%
      vs 99%, p<0.001). In the CA group, we observed a significantly higher incidence
      of confirmed acute or subacute ST than in the control group: 10.9% vs 2.0%
      (p=0.01). None of CA patients had received a dual antiplatelets therapy (0% vs
      99%). LVEF at admission was lower in the CA group (40.3% vs 48%; p<0.001), and
      shock was more frequent (83.6% vs 8.5%; p<0.001). Survival at 28 days was 50.1%
      in CA group vs 98.0% (p<0.001). In multivariate analysis, CA before stenting
      appears to be an independent risk factor for confirmed ST (OR=12.9; 95%CI 1.3
      124.6; p=0.027). CONCLUSION: In CA patients treated with cooling, stenting for
      AMI is associated with a high risk of ST. Shock, insufficient antithrombotic
      treatment, pharmacokinetic changes related to hypothermia may contribute to this
      higher risk. A strategy aiming to reduce this complication may probably improve
      prognosis of patients who underwent coronary sudden death.

PMID- 24572485
TI  - Autoimmune pancreatitis.
AB  - INTRODUCTION: Autoimmune pancreatitis (AIP) is the specific type of chronic
      pancreatitis due to autoimmune background and mechanism. CHARACTERISTICS: The
      main clinical symptoms of AIP are obstructive jaundice and abdominal discomfort.
      The typical histological findings are lymphocytes and IgG4 plasma cells
      infiltration, fibrosis and venulitis within pancreatic gland. Plasma level of
      IgG4 is usually extremely high. OBJECTIVES:  DIAGNOSIS: High level IgG4 positive
      plasma cells in serum, lymphoplasmatic infiltration found on histological
      staining of pancreatic tissue, "sausage-like" pancreas in ultrasound and CT
      scans, and response to steroid therapy are crucial for making of diagnosis.
      Classification of AIP: AIP can be classified into two subtypes. Type 1 was
      recognized as the pancreatic manifestation of multiorgan disorder, called IgG4
      related disease. Type 2 is a pancreas-specific disorder not associated with IgG4,
      with similar histological signs as type 1, but also with the positivity of GEL
      (granulocythic epithelial lesion). RESULTS:  THERAPY: Due to its high effectivity
      in AIP treatment, steroid therapy is the first-line option. The alternative
      therapy is using immunosuppressants (azathioprine). Recently, there are also
      first experience in biological therapy already published. CONCLUSION: Before the
      start of AIP therapy - the differential diagnosis between pancreatic cancer and
      AIP is essential.

PMID- 24572486
TI  - The prevalence of obstructive sleep apnea in patients hospitalized for COPD
      exacerbation.
AB  - BACKGROUND: The concurrence of obstructive sleep apnea (OSA) and chronic
      obstructive pulmonary disease (COPD) is generally identified as an overlap
      syndrome. Only limited evidence is available on the prevalence of OSA in patients
      with stable COPD, and essentially no data on the prevalence of OSA in patients
      hospitalized for COPD exacerbation. The aims of the study were to determine the
      ratio of concurrence of OSA in patients hospitalized for COPD exacerbation and to
      identify the confounders of OSA detected in COPD subjects. METHODS: 101 patients
      were hospitalized for COPD exacerbation at the Department of Respiratory Diseases
      in the course of four months. Seventy-nine consecutive patients were enrolled in
      the study and in 35 of these subjects polygraphy was performed. Descriptive
      statistics, Mann-Whitney test, Kruskal-Wallis test, Spearman correlation and
      Fisher's test were used to summarize and evaluate results. RESULTS: In 18 (51.4%)
      subjects with polygraphy examination, the apnea-hypopnea index (AHI) >= 5
      indicated the presence of OSA. The AHI value, and thus the severity of the sleep
      disorder, correlated with the class of the Mallampati score, presence of snoring,
      apnea, coronary heart disease, diabetes mellitus in patient's history, height,
      body mass index, neck, waist and hip circumferences, and the value of the Epworth
      sleepiness scale. CONCLUSION: Polygraphy performed in patients hospitalized for
      exacerbation of COPD indicated an increased prevalence of OSA compared to the
      general population and stable COPD patients.

PMID- 24572487
TI  - Ultrasound-guided percutaneous ethanol injection of small and medium-sized
      thyroid cysts with relatively small amounts of ethanol.
AB  - BACKGROUND: Ultrasound-guided percutaneous ethanol injection (US-guided PEI) is
      used in patients with recurring symptomatic thyroid cysts in whom simple drainage
      was not successful. It is an alternative non-surgical approach in patients
      refusing or at risk during surgery. METHODS AND RESULTS: US-guided PEI was
      performed in 33 patients, with a success rate of 100% and significantly decreased
      cyst volume after 1, 3 and 6 months after the last PEI compared with the initial
      volume. The mean number of PEI procedures was 1.5+/-0.7 with a mean 96% ethanol
      volume of 2.4+/-1.2 mL. In the entire group, the initial cyst volume was
      significantly reduced to the final volume at 6 months after PEI (10.82+/-5.03 mL
      vs. 0.78+/-0.84 mL; P<0.001). Also in all patients, mean volume reduction rates
      were significantly increased (P<0.001) at check-ups at 1 month (83.1+/-8.1%), 3
      months (89.9+/-6.3%) and 6 months (92.6+/-6.4%). In case of medium-sized cysts,
      more PEI procedures were needed than in small cysts (1.1+/-0.4 vs. 2.0+/-0.5).
      The total amount of 96% ethanol was equal to 22.7+/-7.9% of the initial cyst
      volume. CONCLUSION: Our experiences confirm that small and medium-sized cysts may
      be successfully treated with relatively small amounts of ethanol. In case of
      medium-sized cysts, more PEI procedures were needed. Final reduction of complex
      cysts was achieved later. Apart from temporary localized pain, no serious
      complications were observed in most cases.

PMID- 24572488
TI  - Analysis of thymidine kinase serum levels by novel method DiviTum in multiple
      myeloma and monoclonal gammopathy of undetermined significance - comparison with
      imaging methods 99mTc-MIBI scintigraphy and 18F-FDG PET/CT.
AB  - AIMS: The study aimed at comparing two methods for evaluating thymidinekinase TK
      in serum - an older RIA method and novel DiviTum - in patients with MM and MGUS,
      and also comparing them with biochemical markers and degree of activity evaluated
      by imaging methods 99mTc-MIBI scintigraphy and 18F-FDG PET/CT. METHODS: Serum
      thymidinekinase TK levels were evaluated by DiviTum and an RIA method (TK REA kit
      by Immunotech);The study analyzed correlation of TK activity in serum with
      biochemical markers reflecting activity of MM: beta2-m, LDH, the ratio of kappa
      to lambda (kappa/lambda) free light chains and percentage of bone marrow plasma
      cells (BMPC). 99mTc-MIBI scintigraphy and 18F-FDG PET/CT were performed at the
      time of diagnosis. The degree of activity was expressed semiquantitatively. Scans
      were classified as 0 (normal activity), 1 (diffuse positivity) or 2 (focal
      positivity). RESULTS: We found a strong positive correlation between TK in serum
      evaluated by DiviTum and by TK REA.. The DiviTum analytic method extended the
      detection range and was able to detect higher levels of TK than the RIA method.
      DiviTum technique found positive correlation with beta2-m (r = 0.497) and LDH (r
      = 0.502) and moderate positive correlation with BMPC (r = 0.368). Significantly
      higher TK values measured by TK REA and DiviTum in the group of patients with MM
      (stages I, II or III) than in those with MGUS. Increased TK levels were observed
      in MIBI- or PET/CT-positive patients. Analysis of repeated measurements of TK in
      serum during treatment of MM patients found a correlation between change in TK
      measured by DiviTum and LDH during treatment. CONCLUSIONS: Analysis revealed a
      significant correlation between TK in serum and LDH, beta2-m and BMPC. Increased
      levels of TK in serum were observed in MIBI- or PET/CT-positive patients.
      Combination of positivity of imaging methods which can localize active tumor
      lesions and increased levels of TK in serum can have an impact on decision-making
      and optimization of the therapeutic approach.

PMID- 24572489
TI  - Association of angulation at stent edge and plaque increase or negative
      remodeling.

PMID- 24572490
TI  - Association of angulation at stent edge and plaque increase or negative
      remodeling.

PMID- 24572491
TI  - New biomarker in heart failure with reduced ejection fraction.

PMID- 24572492
TI  - Combined supine and prone myocardial perfusion single-photon emission computed
      tomography with a cadmium zinc telluride camera for detection of coronary artery
      disease.
AB  - BACKGROUND: Myocardial perfusion SPECT (MPS) traditionally requires the patient
      to be in the supine position, but diaphragmatic attenuation of the inferior wall
      reduces test specificity. The aim of this study was to assess the feasibility of
      combined MPS in the supine and prone positions using a novel cadmium zinc
      telluride (CZT) camera. METHODS AND RESULTS: A total of 276 consecutive patients
      with suspected/known coronary artery disease (CAD) who underwent single-day
      (99m)Tc-tetrofosmin or (99m)Tc-sestamibi stress/rest CZT SPECT, were enrolled in
      the study. Seventy-six underwent coronary angiography. Five-minute scan in the
      supine (S) position and thereafter in the prone (P) position produced images that
      were visually interpreted to obtain summed stress (SSS) and rest (SRS) scores. A
      combined stress score (C-SSS) was calculated by grouping anterior perfusion
      defects observed during supine imaging with inferior half segments observed
      during prone imaging. The SSS for the supine, prone, and combined protocols were
      9+/-8, 7+/-8, and 7+/-8, respectively (P<0.0001). The SRS were 5+/-8, 4+/-7, and
      6+/-7, respectively (P=0.005). The area under the ROC curve for the S-SSS, P-SSS,
      and C-SSS scores was 0.815 (95% CI: 0.713-0.917), 0.813 (0.711-0.914), and 0.872
      (0.783-0.961), respectively. Corresponding sensitivities and specificities for
      detecting CAD were 87% and 50%, 80% and 77%, and 85% and 82%, respectively. C-SSS
      had significantly better specificity and accuracy than S-SSS (P<0.05).
      CONCLUSIONS: Combined imaging with a CZT camera is suitable for routine clinical
      MPS and provides greater diagnostic accuracy than supine imaging alone.

PMID- 24572493
TI  - Adsorption and enzyme activity of sucrose phosphorylase on lipid Langmuir and
      Langmuir-Blodgett films.
AB  - The production of bioelectronic devices, including biosensors, can be conducted
      using enzymes immobilized in ultrathin solid films, for which preserving the
      enzymatic catalytic activity is crucial for optimal performance. In this sense,
      nanostructured films that allow for control over molecular architectures are of
      interest. In this paper, we investigate the adsorption of sucrose phosphorylase
      onto Langmuir monolayers of the phospholipid dimyristoylphosphatidic acid, which
      caused the surface pressure isotherms to expand. With polarization-modulated
      infrared reflection absorption spectroscopy (PM-IRRAS), the amide bands from the
      enzyme could be identified, with the C-N and C=O dipole moments lying parallel to
      the air-water interface. Structuring of the enzyme into an alpha-helix was noted,
      and this structure was preserved when the mixed enzyme-phospholipid monolayer was
      transferred in the form of a Langmuir-Blodgett (LB) film. The latter was
      demonstrated with measurements of the catalytic activity of sucrose
      phosphorylase, which presented the highest enzyme activity for multilayer LB
      film. The approach presented in this study not only allows for optimized
      catalytic activity toward sucrose but also permits to explain why certain film
      architectures exhibit superior performance. 

PMID- 24572494
TI  - Synthesis of composite gelatin-hyaluronic acid-alginate porous scaffold and
      evaluation for in vitro stem cell growth and in vivo tissue integration.
AB  - Engineering three-dimensional (3-D) porous scaffolds with precise bio-functional
      properties is one of the most important issues in tissue engineering. In the
      present study, a three-dimensional gelatin-hyaluronic acid-alginate (GHA)
      polymeric composite was synthesized by freeze-drying, which was followed by ionic
      crosslinking using CaCl2, and evaluated for its suitability in bone tissue
      engineering applications. The obtained matrix showed high porosity (85%), an
      interconnected pore morphology and a rapid swelling behavior. The rheological
      analysis of GHA showed a viscoelastic characteristic, which suggested a high load
      bearing capacity without fractural deformation. The influence of the GHA matrix
      on cell growth and on modulating the differentiation ability of mesenchymal stem
      cells was evaluated by different biochemical and immunostaining assays. The
      monitoring of cells over a period of four weeks showed increased cellular
      proliferation and osteogenic differentiation without external growth factors,
      compared with control (supplemented with osteogenic differentiation medium). The
      in vivo matrix implantation showed higher matrix-tissue integration and cell
      infiltration as the duration of the implant increased. These results suggest that
      a porous GHA matrix with suitable mechanical integrity and tissue compatibility
      is a promising substrate for the osteogenic differentiation of stem cells for
      bone tissue engineering applications.

PMID- 24572495
TI  - Effects of the sol-gel route on the structural characteristics and antibacterial
      activity of silica-encapsulated gentamicin.
AB  - The effects of sol-gel processes, i.e., acid-catalyzed gelation, base-catalyzed
      gelation and base-catalyzed precipitation routes, on the encapsulation of
      gentamicin were investigated. The resulting xerogels were characterized using a
      series of complementary instrumental techniques, i.e., the adsorption/desorption
      of nitrogen, small-angle X-ray scattering, Fourier transform infrared
      spectroscopy, diffuse reflectance spectroscopy, X-ray photoelectron spectroscopy,
      atomic force microscopy and scanning electron microscopy. The encapsulated
      gentamicin samples were tested against a series of Gram-positive and Gram
      negative bacterial strains. The best antimicrobial activity was observed with the
      encapsulated gentamicin that was prepared via the precipitation route, even in
      comparison with the neat antibiotic, especially in the case of the Gram-positive
      strain Staphylococcus aureus. The gentamicin concentration on the outermost
      surface and the zeta potential were identified as factors that affected the
      highest efficiency, as observed in the case of encapsulation via the base
      catalyzed process. 

PMID- 24572500
TI  - Postural perturbations induced by a moving virtual environment are reduced in
      persons with brain injury when gripping a mobile object.
AB  - BACKGROUND AND PURPOSE: Gripping a mobile (unfixed) object increases standing
      postural stability in healthy individuals. We tested whether the same strategy is
      effective for stabilizing upright posture perturbed by a moving environment
      (virtual perturbation) in participants with traumatic brain injury (TBI).
      METHODS: Fifteen participants with mild-to-moderate postural deficits after TBI
      and a comparison group of 15 age-matched healthy subjects participated in the
      study. Participants stood for 1 minute in front of a large screen with a
      projected three-dimensional image of a boat; for 30 seconds the boat remained
      stationary (no visual stimulation condition), and for 30 seconds the boat rocked
      on the water at a speed of 15 degrees /s (visual stimulation condition). The
      visual stimulation was applied in pseudorandom order (during either the first or
      second half of the 1-minute trial). To analyze postural stability, the
      displacement and velocity of the center of mass in the sagittal and frontal
      planes were compared between groups and across 4 experimental conditions,
      including standing with/without visual stimulation and with/without gripping a
      300-g object (short wooden stick) in the dominant hand. RESULTS: Participants
      with TBI showed greater instability under all experimental conditions. The visual
      stimulation significantly increased postural oscillations in the sagittal plane
      by 35% to 63% across groups. Gripping a stick significantly reduced the
      stimulation-induced instability in the sagittal plane by 19% to 29%, although not
      to the level of the no-stimulation condition in either group. CONCLUSION: The
      stabilizing effect of gripping an external object in participants with TBI was
      confirmed. A possibility of using this effect as a balance aid strategy requires
      further investigation.

PMID- 24572497
TI  - Immobilisation of a fibrillin-1 fragment enhances the biocompatibility of PTFE.
AB  - Current vascular biomaterials exhibit poor biocompatibility characterised by
      failure to promote endothelialisation, predisposition to neoinitmal hyperplasia
      and excessive thrombogenicity. Fibrillin-1, a major constituent of microfibrils
      is associated with elastic fibres in the arterial wall. Fibrillin-1 binds to
      endothelial cells through an RGD cell adhesion motif in the fourth TB module. The
      RGD motif is present in PF8, a recombinant fibrillin-1 fragment. We investigated
      the potential of PF8 to improve the biocompatibility of PTFE. PF8 enhanced
      endothelial cell attachment and cell proliferation to a greater extent than
      fibronectin (p<0.01). PF8 immobilised on PTFE using plasma immersion ion
      implantation (PIII), retained these favourable cell interactive properties, again
      promoting endothelial cell attachment and proliferation. The thrombogenicity of
      covalently bound PF8 on PTFE was assessed in both static and dynamic conditions.
      In static conditions, uncoated PIII treated PTFE was more thrombogenic than
      untreated PTFE, while PF8 coating reduced thrombogenicity. Under flow, there was
      no difference in the thrombogenicity of PF8 coated PTFE and untreated PTFE.
      Immobilised PF8 shows a striking ability to promote attachment and growth of
      endothelial cells on PTFE, while providing a non-thrombogenic surface. These
      features make PF8 a promising candidate to improve the biocompatibility of
      current synthetic vascular grafts.

PMID- 24572496
TI  - Poly(l-lactide-co-2-(2-methoxyethoxy)ethyl methacrylate): a biodegradable polymer
      with protein resistance.
AB  - We have synthesized poly(l-lactide-co-2-(2-methoxyethoxy)ethyl methacrylate) (LA
      co-MEO2MA) containing both degradable and protein resistant units via hybrid
      copolymerization with (1-tert-butyl-4,4,4-tris(dimethylamino)-2,2
      bis[tris(dimethylamino)phophoranylidenamino]-2Lambda5,Lambda5
      catenadi(phosphazene) (t-BuP4) as the catalyst. Nuclear magnetic resonance (NMR)
      and differential scanning calorimetry (DSC) show that LA-co-MEO2MA is a random
      copolymer. The studies of quartz crystal microbalance with dissipation (QCM-D)
      demonstrate that the copolymer enzymaticlly degrades much faster than poly(l
      lactide) (PLA) homopolymer due to its lower crystallinity. We have also
      investigated the adsorption of bovine serum albumin (BSA), lysozyme or fibrinogen
      on a LA-co-MEO2MA surface in real time by use of QCM-D and surface plasmon
      resonance (SPR). Our studies reveal that the polymer is protein resistant
      depending on MEO2MA content. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl
      tetrazolium bromide (MTT) assay experiments demonstrate that the polymer has a
      low cytotoxicity.

PMID- 24572503
TI  - From the editor.

PMID- 24572504
TI  - Advances in pain medicine: Epiduroscopy.

PMID- 24572501
TI  - Comparison of imported Plasmodium ovale curtisi and P. ovale wallikeri infections
      among patients in Spain, 2005-2011.
AB  - Sequencing data from Plasmodium ovale genotypes co-circulating in multiple
      countries support the hypothesis that P. ovale curtisi and P. ovale wallikeri are
      2 separate species. We conducted a multicenter, retrospective, comparative study
      in Spain of 21 patients who had imported P. ovale curtisi infections and 14 who
      had imported P. ovale wallikeri infections confirmed by PCR and gene sequencing
      during June 2005-December 2011. The only significant finding was more severe
      thrombocytopenia among patients with P. ovale wallikeri infection than among
      those with P. ovale curtisi infection (p = 0.031). However, we also found
      nonsignificant trends showing that patients with P. ovale wallikeri infection had
      shorter time from arrival in Spain to onset of symptoms, lower level of albumin,
      higher median maximum core temperature, and more markers of hemolysis than did
      those with P. ovale curtisi infection. Larger, prospective studies are needed to
      confirm these findings. 

PMID- 24572505
TI  - Advances in pain medicine: Pharmacologic and transplantation advances.

PMID- 24572502
TI  - The potential for dietary factors to prevent or treat osteoarthritis.
AB  - Osteoarthritis (OA) is a degenerative joint disease for which there are no
      disease-modifying drugs. It is a leading cause of disability in the UK.
      Increasing age and obesity are both major risk factors for OA and the health and
      economic burden of this disease will increase in the future. Focusing on
      compounds from the habitual diet that may prevent the onset or slow the
      progression of OA is a strategy that has been under-investigated to date. An
      approach that relies on dietary modification is clearly attractive in terms of
      risk/benefit and more likely to be implementable at the population level.
      However, before undertaking a full clinical trial to examine potential efficacy,
      detailed molecular studies are required in order to optimise the design. This
      review focuses on potential dietary factors that may reduce the risk or
      progression of OA, including micronutrients, fatty acids, flavonoids and other
      phytochemicals. It therefore ignores data coming from classical inflammatory
      arthritides and nutraceuticals such as glucosamine and chondroitin. In
      conclusion, diet offers a route by which the health of the joint can be protected
      and OA incidence or progression decreased. In a chronic disease, with risk
      factors increasing in the population and with no pharmaceutical cure, an
      understanding of this will be crucial. 

PMID- 24572506
TI  - Epiduroscopy.

PMID- 24572507
TI  - Long deep breathing.

PMID- 24572509
TI  - Symposium on osteoporosis: fractures, back pain, disability - management.

PMID- 24572511
TI  - Getting writing right.

PMID- 24572512
TI  - Misread labels as a cause of medication errors.
AB  - The dangerous convergence of small typefaces, dim lighting, aging nurses. 

PMID- 24572510
TI  - ATM specifically mediates repair of double-strand breaks with blocked DNA ends.
AB  - Ataxia telangiectasia is caused by mutations in ATM and represents a paradigm for
      cancer predisposition and neurodegenerative syndromes linked to deficiencies in
      the DNA-damage response. The role of ATM as a key regulator of signalling
      following DNA double-strand breaks (DSBs) has been dissected in extraordinary
      detail, but the impact of this process on DSB repair still remains controversial.
      Here we develop novel genetic and molecular tools to modify the structure of DSB
      ends and demonstrate that ATM is indeed required for efficient and accurate DSB
      repair, preventing cell death and genome instability, but exclusively when the
      ends are irreversibly blocked. We therefore identify the nature of ATM
      involvement in DSB repair, presenting blocked DNA ends as a possible pathogenic
      trigger of ataxia telangiectasia and related disorders. 

PMID- 24572513
TI  - Best practice vs. reality.

PMID- 24572514
TI  - Best practice vs. reality.

PMID- 24572515
TI  - Best practice vs. reality.

PMID- 24572516
TI  - Best practice vs. reality.

PMID- 24572517
TI  - Newly Licensed RNs.

PMID- 24572518
TI  - Eyes wide shut.
AB  - Evidence mounts that sleep deprivation leaves nurses error prone. 

PMID- 24572520
TI  - More work needed to equalize U.S. health care.
AB  - Accurate assessments require cultural awareness and communication skills. 

PMID- 24572522
TI  - Multivitamins may not prevent disease, new studies suggest.
AB  - No evidence that they prevent cognitive decline or cardiovascular events after
      myocardial infarction. 

PMID- 24572524
TI  - New global survey shows an increasing cancer burden.
AB  - Data show a 20% increase in breast cancer from 2008 to 2012. 

PMID- 24572526
TI  - Tobacco control: where are we now and where are we going?

PMID- 24572533
TI  - The systematic review: an overview.
AB  - This article is the first in a new series on systematic reviews from the Joanna
      Briggs Institute, an international collaborative supporting evidence-based
      practice in nursing, medicine, and allied health fields. The purpose of the
      series is to show nurses how to conduct a systematic review-one step at a time.
      This first installment provides a synopsis of the systematic review as a
      scientific exercise, one that influences health care decisions. 

PMID- 24572536
TI  - The new epidemic.
AB  - Editor's note: From its first issue in 1900 through to the present day, AJN has
      unparalleled archives detailing nurses' work and lives over the last century.
      These articles not only chronicle nursing's growth as a profession within the
      context of the events of the day, but they also reveal prevailing societal
      attitudes about women, health care, and human rights. Today's nursing school
      curricula rarely include nursing's history, but it's a history worth knowing. To
      this end, From the AJN Archives will be a frequent column, containing articles
      selected to fit today's topics and times.This month's article, from the November
      1982 issue, is the first AJN article published on AIDS. It was early in the
      epidemic; only 608 cases of Kaposi's sarcoma and opportunistic infections had
      been reported to the Centers for Disease Control and Prevention-a mere trickle in
      the flood that was to come. Reading it now, aware of all we've learned since, we
      have a sense of how much we were fumbling around in the dark in those early days,
      searching for a cause and a cure, often going in wrong directions. The closest we
      had come to the true nature of the syndrome was an understanding that "life-style
      factors seem to be involved and the agent appears to be infectious." To read the
      complete article from our archives, go to http://bit.ly/1iswhZe.

PMID- 24572541
TI  - Clostridium difficile infection is on the rise.
AB  - The emergence of an epidemic strain makes prevention and early diagnosis
      critical. 

PMID- 24572542
TI  - Red Cross nurses: leading change to advance health.
AB  - American nurses are recognized for service and leadership. 

PMID- 24572543
TI  - My first preceptor.
AB  - A patient emergency alters the dynamic of a less-than-nurturing relationship. 

PMID- 24572544
TI  - Equipment and preliminary results for orthogonal pressurized planar
      electrochromatography.
AB  - We report combination of overpressured layer chromatography (OPLC) and
      pressurized planar electrochromatography (PPEC) techniques into a single
      technique in which both OPLC and PPEC processes proceed simultaneously and
      orthogonally. The separation process with this new technique is performed in
      adsorbent layer of a chromatographic plate, which is equipped with special
      sealing margin on its whole periphery and closed under pressure in special
      chamber. We have named this separation technique as orthogonal pressurized planar
      electrochromatography (OPPEC). Examples of analytical and micropreparative
      (continuous) OPPEC separations are demonstrated. 

PMID- 24572545
TI  - The on-bead digestion of protein corona on nanoparticles by trypsin immobilized
      on the magnetic nanoparticle.
AB  - Proteins interacting with nanoparticles would form the protein coronas on the
      surface of nanoparticles in biological systems, which would critically impact the
      biological identities of nanoparticles and/or result in the physiological and
      pathological consequences. The enzymatic digestion of protein corona was the
      primary step to achieve the identification of protein components of the protein
      corona for the bottom-up proteomic approaches. In this study, the investigation
      on the tryptic digestion of protein corona by the immobilized trypsin on a
      magnetic nanoparticle was carried out for the first time. As a comparison with
      the usual overnight long-time digestion and the severe self-digestion of free
      trypsin, the on-bead digestion of protein corona by the immobilized trypsin could
      be accomplished within 1h, along with the significantly reduced self-digestion of
      trypsin and the improved reproducibility on the identification of proteins by the
      mass spectrometry-based proteomic approach. It showed that the number of
      identified bovine serum (BS) proteins on the commercial Fe3O4 nanoparticles was
      increased by 13% for the immobilized trypsin with 1h digestion as compared to
      that of using free trypsin with even overnight digestion. In addition, the on
      bead digestion of using the immobilized trypsin was further applied on the
      identification of human plasma protein corona on the commercial Fe3O4
      nanoparticles, which leads the efficient digestion of the human plasma proteins
      and the identification of 149 human plasma proteins corresponding to putative
      critical pathways and biological processes. 

PMID- 24572546
TI  - Evaluation of the kinetic performance of new prototype 2.1mm*100mm narrow-bore
      columns packed with 1.6MUm superficially porous particles.
AB  - The mass transfer mechanism in three prototype narrow-bore columns (2.1mm*100mm
      format) packed with 1.6MUm superficially porous particles was investigated using
      different instruments. The heights equivalent to a theoretical plate of three
      small molecules were measured using a mixture of acetonitrile and water as the
      eluent. The values reported include the contributions of longitudinal diffusion,
      eddy dispersion, and the solid-liquid mass transfer resistance. The bulk
      diffusion coefficients of the analytes were measured using the capillary method,
      calibrated with thiourea in pure water. The reduced longitudinal diffusion
      coefficient was determined from the results of a series of peak parking
      experiments. The solid-liquid mass transfer resistance coefficient and the intra
      particle diffusivities of the analytes in the porous region of the particles were
      estimated from Garnett-Torquato's model of effective diffusion in dense beds
      packed with core-shell particles. The eddy dispersion term, mostly due to trans
      column and border effects, was obtained by subtracting the longitudinal diffusion
      and the solid-liquid mass transfer resistance terms from the total HETP obtained
      from the first and second central peak moments calculated by numerical
      integration (Simpson's approach) after baseline correction and systematic left
      and right cuts of the peak profiles. The results show that the eddy dispersion
      controls at least 66% of the overall column HETP for small molecules beyond the
      optimum velocity. This work illustrates how important it is to use ultra-low
      dispersive very high pressure liquid chromatography (vHPLC) systems to properly
      measure and to practically use the high efficiencies of narrow-bore columns
      packed with 1.6MUm core-shell particles since these columns provide intrinsic
      efficiencies higher than 400,000 plates per meter. 

PMID- 24572547
TI  - A versatile method for protein-based antigen bioanalysis in non-clinical
      pharmacokinetics studies of a human monoclonal antibody drug by an immunoaffinity
      liquid chromatography-tandem mass spectrometry.
AB  - A versatile immunoaffinity liquid chromatography-tandem mass spectrometry (LC
      MS/MS) method was developed to quantify the total concentration of a protein
      based antigen in non-clinical pharmacokinetics (PK) studies of a human monoclonal
      antibody drug. The method combines using magnetic beads that have been coated
      with a commercial anti-human Fc region antibody to capture an immune complex of
      the antigen and antibody drug, with subsequent digestion and quantification of
      the antigen-derived tryptic peptide via LC-MS/MS. Although a typical immunoassay
      or an immunoaffinity LC-MS/MS assay requires an antigen-specific antibody that
      uses a different epitope from the antibody drug, this method requires only a
      commercial anti-human Fc region antibody. The method was applied to quantify
      total receptor activator of nuclear factor-kappaB ligand (RANKL) in the presence
      of denosumab, a humanized monoclonal antibody (mAb) specific to RANKL. The assay
      was validated as fit-for-purpose and found to be accurate (<115% interbatch
      accuracies) and precise (<15%, interbatch coefficient of variation) across a
      range of 3.13-200ng/mL RANKL. Commercial enzyme-linked immunosorbent assay
      (ELISA) kit was not able to determine the total RANKL because interference by
      denosumab decreased recovery. In contrast, the antibody drug had less effect on
      the LC-MS/MS method. The method now provides a bioanalytical platform for
      developing other protein-based antigen assays in the early drug stage. 

PMID- 24572549
TI  - From the editor.

PMID- 24572548
TI  - The angiotensinogen gene polymorphism is associated with heart failure among
      Asians.
AB  - The angiotensinogen (AGT) gene M235T polymorphism has been suggested to be linked
      to risk of heart failure (HF). However, association studies on the M235T
      polymorphism and HF risk have shown conflicting results. PubMed and China Biology
      Medicine (CBM) databases were systematically searched to identify relevant
      studies. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess
      the strength of the association. A total of 1,281 HF cases and 1,376 controls
      were included in the analysis. The pooled data showed that there was no
      significant associations between the AGT M235T polymorphism and HF risk for TT
      vs. MM (OR = 1.17, 95%CI = 0.62-2.19, P = 0.635), MT vs. MM (OR = 0.97, 95%CI =
      0.77-1.22, P = 0.776), MT/TT vs. MM (OR = 1.07, 95%CI = 0.67-1.69, P = 0.781),
      and TT vs. MM/MT (OR = 1.23, 95%CI = 0.86-1.76, P = 0.259). In contrast, in the
      HF subgroup analysis by ethnicity, the AGT M235T polymorphism had a decreased
      risk of HF among Asians (MT vs. MM, OR = 0.39, 95%CI = 0.17-0.92, P = 0.032). Our
      results suggest that the AGT M235T polymorphism is a low-penetrant risk factor
      for the development of HF among Asians. 

PMID- 24572550
TI  - Another opinion on non-malignant pain management?

PMID- 24572551
TI  - The influence of the spine on the shoulder in the throwing athlete.
AB  - Analysis of shoulder dysfunction in throwing and overhead athletes can no longer
      be restricted to evaluation of the glenohumeral joint alone. The isolated
      shoulder is incapable of generating the force necessary to hurl a baseball at
      velocities of 90-100 miles per hour or serve a tennis ball in excess of 120 miles
      per hour. The purpose of this paper is to provide a literature based theoretical
      framework for the role of the spine during these activities. The spine is a
      pivotal component of the kinematic chain which functions as a transfer link
      between the lower and upper limbs, a force generator capable of accelerating the
      arm, and a force attenuator which dampens shear forces at the glenohumeral joint
      during the deceleration phase of the pitching motion. Side bending and rotation
      of the cervical spine facilitates visual acquisition of the intended target.
      Inflexibility of the hip musculature and weakness of the muscles which attach to
      the thoracolumbar fascia have profound effects upon spine function which
      secondarily places greater stress upon the glenohumeral joint and rotator cuff.
      Shoulder rehabilitation and injury prevention programs should include evaluation
      of and exercise regimens for the lumbar, thoracic and cervical spine. 

PMID- 24572552
TI  - Guidelines for program evaluation in chronic non-malignant pain management.
AB  - The current article offers guidelines to systematically evaluate programs which
      treat chronic non-malignant pain syndrome patients. The guidelines represent a
      basic program evaluation strategy and include specific recommendations and
      choices on measurement-assessment tools based upon available research literature
      and common clinical practice. They are based on evaluation by objectives, which
      include the program's ability to reduce the misuse of medications, increase
      physical function, increase productive activity at home, work and socially,
      improve overall mood, reduce subjective pain intensity, reduce the use of
      healthcare, when applicable, achieve equitable case settlement, and minimize pain
      treatment program cost without compromising quality of care. The method and
      timing of assessing each of these objectives are delineated with an emphasis on
      using reliable, valid measures which can be applied effectively within a clinical
      setting. The guidelines also advocate patient and staff satisfaction assessment,
      thus offering a fully integrated program evaluation system which can measure
      effectiveness and allow ongoing improvement in care. 

PMID- 24572553
TI  - The sensory consequences of repetitive strain injury in musicians: focal dystonia
      of the hand.
AB  - Some individuals with repetitive strain injury (RSI) develop focal dystonia of
      the hand (FDh), a disorder of motor control manifested in a specific context
      during skilled, hand movements. This descriptive study was designed to determine
      if musicians with FDh had reduced tactile discrimination. Ten healthy adults and
      ten patients with FDh participated in the study. From the standardized Sensory
      Integration and Praxis Test, five subtests were selected to measure tactile
      discrimination. The Paired Wilcoxon Test was used to analyze, meaningful, planned
      pairwise differences by side and by group. The two groups performed similarly on
      the three tests measuring tactile motor perception (Finger Identification,
      Localization and Kinesthesia). However, those with FDh performed significantly
      worse than the healthy comparison group on two tactile perceptual tasks: (1)
      Graphesthesia, right affected (P < 0.003) and left unaffected (p < 0.005); and
      (2) Manual Form Perception (stereognosis) on the right affected (P < 0.002) and
      left unaffected (P < 0.002). It is possible that the somatosensory differences as
      measured by tactile discrimination tasks represent some degradation of the hand
      representation following prolonged, repetitive, near simultaneous sensory
      stimulation of adjacent digits. Tactile discrimination should be tested in
      patients with RSI to detect potential risks for developing FDh. Effective
      treatment of patients with RSI including FDh may need to target the somatosensory
      deficits in order to restore stress-free motor movements. 

PMID- 24572554
TI  - Utilizing psychological assessment in rehabilitating patients with occupational
      musculoskeletal injuries.
AB  - Patients with occupational musculoskeletal injuries who participate in
      multidisciplinary rehabilitation programs will likely undergo psychological
      assessment as a part of the evaluation process. Although the importance of
      examining non-physical influences on the patient's recovery is widely recognized
      among clinicians, it is often unclear how findings from psychological assessment
      are being utilized to facilitate rate of recovery from injury. The purpose of
      this study was to encourage a re-examination of current psychological assessment
      practices among multidisciplinary rehabilitation programs and to describe how the
      Minnesota Multiphasic Personality Inventory (MMPI-2) was utilized with a work
      hardening patient sample (n = 86). For the overall patient sample, the MMPI-2
      depicted relatively high levels of somatic focus and low levels of psychological
      distress. To enhance clinical utility, a clustering method identified profile
      groupings that were distinguishable on the basis of known personality and
      behavioral correlates. Two profile groupings (Scale 1; Scales 1-3/3-1) were
      discussed with recommendations for how clinicians may facilitate rate of recovery
      from injury. The MMPI-2 appears to be particularly useful in identifying
      treatment conditions that may favorably influence rate of recovery from
      occupational musculoskeletal injuries. 

PMID- 24572555
TI  - A maladaptive gait abnormality in patients with lumbar spinal stenosis.
AB  - A maladaptive pattern of abnormally increased anterior pelvic tilt during gait
      was documented using quantitative gait analysis in two patients presenting with
      lumbar spinal stenosis. Both patients also had, by physical examination, mild
      bilateral hip flexion contracture impairments which mayor may not have been
      directly related to the spinal stenosis. There is no literature to date
      supporting the presence of either hip flexion contractures or excessive anterior
      pelvic tilt during gait in patients with lumbar spinal stenosis. The excessive
      anterior pelvic tilt present in these patients was presumably a compensation for
      the hip flexion contractures to achieve reasonable step lengths. Increased
      anterior pelvic tilt induces increased hyperextension of the lumbosacral spine,
      which in a patient with spinal stenosis, could cause pain and lead to further
      spinal nerve impingement. Since hip flexion contracture impairments are amenable
      to stretching, their presence should be especially pursued in patients with
      spinal stenosis. 

PMID- 24572557
TI  - Alternative medicine.
AB  - This is the first installment of a new section on Alternative Medicine.
      Alternative medicine practices are fast becoming the treatment of choice for many
      Americans, as will be discussed below. As clinicians devoted to rehabilitating
      patients to their fullest potential, it is an avenue that deserves further
      exploration into the benefits and controversies surrounding it. Future columns
      will delve further into the disadvantages, advantages, varying methods available,
      and current research in Alternative Medicine. 

PMID- 24572556
TI  - Intra-articular ganglion cyst arising from the anterior cruciate ligament: a case
      report.
AB  - Intra-articular ganglion cysts have been reported in the medical literature but
      are extremely rare. A MEDLINE search from 1966 to July 1995 revealed no reported
      cases in the Physical Medicine literature. This case report details the
      presentation, evaluation and treatment course of a patient with knee complaints
      who was subsequently diagnosed to have a ganglion cyst arising from the anterior
      cruciate ligament. The patient was a 38-year-old woman with a 6-month history of
      knee swelling and pain. She had difficulty walking. Non-steroidal anti
      inflammatory agents had not alleviated her symptoms significantly. Physiatric
      evaluation revealed a supra-patellar effusion and a mass lateral to the patellar
      tendon. MRI evaluation revealed an intra-articular cyst. The patient underwent
      surgical removal of what was subsequently determined to be an intra-articular
      ganglion cyst arising from the anterior cruciate ligament. The patient has had
      progressive resolution of her knee symptoms post-operatively. Physiatrists need
      to be aware of this cause of mechanical knee symptoms. 

PMID- 24572558
TI  - Computer use and applications for physicians.
AB  - This article reviews widely available medical computer applications and discusses
      their use for individual physicians and physician groups. The medical
      applications reviewed include electronic mail, electronic medical references,
      medical literature databases, and medical areas of interest on the Internet. The
      reader is directed to other key sources for review of office management software
      solutions. 

PMID- 24572561
TI  - Demyelination in a patient receiving ustekinumab for refractory Crohn's disease.

PMID- 24572562
TI  - Adiposity and hepatic lipid in healthy full-term, breastfed, and formula-fed
      human infants: a prospective short-term longitudinal cohort study.
AB  - BACKGROUND: The effect of mode of infant feeding on adiposity deposition is not
      fully understood. OBJECTIVE: The objective was to test the hypothesis that
      differences in total and regional adipose tissue content and intrahepatocellular
      lipid (IHCL) arise in early infancy between breast- and formula-fed infants and
      to describe longitudinal changes. DESIGN: This prospective longitudinal cohort
      study was performed in 2 hospitals in the United Kingdom. Healthy, full-term,
      appropriate weight-for-gestational age infants were recruited; adipose tissue
      volume and distribution were directly quantified by using whole-body magnetic
      resonance imaging; IHCL was assessed by in vivo proton magnetic resonance
      spectroscopy. Measurements were performed after birth (median age: 13 d) and at 6
      12 wk of age. Method of infant feeding was recorded prospectively by using
      maternally completed feeding diaries. Breastfed was defined as >80% of feeds
      consisting of breast milk at both points; formula-fed was defined as >80% of
      feeds consisting of formula milk at both points. RESULTS: Longitudinal results
      were obtained from 70 infants (36 breastfed, 9 mixed-fed, and 25 formula-fed). No
      differences were found in total or regional adipose tissue or IHCL between
      breastfed and formula-fed infants. In pooled analyses including all feeding
      groups, IHCL and total adipose tissue approximately doubled between birth and 6
      12 wk: IHCL after birth (median: 0.949; IQR: 0.521-1.711) and at 6-12 wk (1.828;
      1.376-2.697; P < 0.001) and total adipose tissue after birth (0.749 L; 0.620
      0.928 L) and at 6-12 wk (1.547 L; 1.332-1.790 L; P < 0.001). Increasing adiposity
      was characterized by greater relative increases in subcutaneous than in internal
      adipose tissue depots. CONCLUSIONS: No differences were detectable in adipose
      tissue or IHCL accretion between breastfed and formula-fed infants up to 2 mo.
      The substantial increase in IHCL seen over this period in both breastfed and
      formula-fed infants is a novel observation, which suggests that hepatic storage
      of lipids may be physiologic up to 2 mo. This trial was registered at
      www.clinicaltrials.gov as NCT02033005.

PMID- 24572563
TI  - Reviews examining sugar-sweetened beverages and body weight: correlates of their
      quality and conclusions.
AB  - BACKGROUND: The role of sugar-sweetened beverages (SSBs) in increasing obesity is
      of great scientific, clinical, and public health interest. Many reviews have been
      published on this topic in recent years with very different conclusions.
      OBJECTIVE: We sought to assess the scientific quality and other characteristics
      that may be associated with the conclusions of reviews regarding the causal
      relation between SSB consumption and body weight. DESIGN: A systematic search of
      reviews in English language-published peer-reviewed journals in 2006-2013 was
      performed. Their methodologic quality was assessed by 2 judges using 2 scoring
      systems: the Assessment of Multiple Systematic Reviews and the American Dietetic
      Association Quality Criteria Checklist. The conclusions were blindly assessed by
      11 independent readers using a Likert scale ranging from a position score of 0 =
      no evidence of a causal relation to 5 = strong evidence of a causal relation.
      RESULTS: Twenty reviews were identified: 5 meta-analyses, 3 qualitative
      systematic reviews, and 12 qualitative nonsystematic reviews. Four received
      funding from the food industry. Quality scores were neither correlated with the
      readers' perception of conclusions nor with the source of funding. However,
      industry-funded reviews were more likely to suggest that evidence supporting a
      causal relation between SSB consumption and weight gain was weak (mean position
      score = 1.78), whereas evidence was generally considered well-founded in other
      reviews (mean position score = 3.39; P <= 0.01). CONCLUSIONS: For a complex and
      controversial scientific issue, it is important to minimize perceived or actual
      threats to scientific objectivity and methodologic quality. More refined tools
      are needed to better assess their scientific quality and to identify factors and
      mechanisms that may influence authors' conclusions.

PMID- 24572564
TI  - Protein requirements: methodologic controversy amid a call for change.

PMID- 24572565
TI  - Obesity paradox in cancer: new insights provided by body composition.
AB  - BACKGROUND: Obesity, defined by body mass index (BMI), appears to have a
      paradoxical protective effect in several chronic diseases. OBJECTIVE: We
      investigated the obesity paradox in cancer patients by using body composition.
      DESIGN: The study was an observational study of 175 cancer patients assessed
      before chemotherapy. Obesity was defined as BMI (in kg/m(2)) >=30 or fat mass
      index (FMI; fat mass divided by the square of height) >=5.2 (men) and >=8.2
      (women) measured by using a bioelectrical impedance analysis. Low muscle mass
      (sarcopenia) was defined as fat-free mass index (fat-free mass divided by the
      square of height) <17.5 (men) and <15.1 (women). RESULTS: Most patients were
      women (65.7%) and had a mean (+/-SD) age of 56.9 +/- 12.8 y. According to BMI
      criteria, 60% of patients were overweight or obese. The median survival time for
      overweight (2.64 y; range: 0.23-3.16 y) and obese (2.61 y; range: 0.26-3.20 y)
      patients was significantly higher than for patients with a normal (2.04 y; range:
      0.06-3.05 y) or low (0.52 y; range: 0.19-0.98 y) BMI (P < 0.001). Sarcopenic
      patients had shorter survival, regardless of their FMI. Obesity predicted higher
      survival rates only when sarcopenia was absent. In a multivariate Cox regression
      model, sarcopenia was an independent predictor of higher mortality (HR: 5.19; 95%
      CI: 2.58, 10.43) after we controlled for BMI, age, and tumor stage. CONCLUSIONS:
      The obesity paradox is present in cancer patients only when obesity is defined by
      BMI. Patients with sarcopenic obesity had the poorest prognosis. Cancer patients
      with high mortality risk can be identified by a body-composition assessment.

PMID- 24572566
TI  - BMI, age, and mortality: the slaying of a beautiful hypothesis by an ugly fact.

PMID- 24572567
TI  - From Woese to Wired: the unexpected payoffs of basic research.
AB  - Fundamental observations about nature sometimes take a circuitous and utterly
      unpredictable course from bright idea to demonstrably practical impact. The tale
      of how Carl Woese's basic insights about microbial diversity eventually
      contributed to the emergence of a new field of science with numerous potential
      applications is just such a story. 

PMID- 24572568
TI  - Regioselective synthesis of oxazole derivatives via palladium-catalyzed and
      copper-mediated cascade oxidative cyclization.
AB  - A novel Pd-catalyzed/Cu-mediated oxidative cyclization has been developed for the
      synthesis of trisubstituted oxazoles, which is thought to proceed through cascade
      formation of C-N and C-O bonds. In this protocol, four hydrogen atoms were
      removed and water was used as the oxygen atom source. 

PMID- 24572569
TI  - Layering in the Paleocene/Eocene boundary of the Millville core is drilling
      disturbance.

PMID- 24572570
TI  - Onset of carbon isotope excursion at the Paleocene-Eocene thermal maximum took
      millennia, not 13 years.

PMID- 24572571
TI  - Unsettled puzzle of the Marlboro clays.

PMID- 24572572
TI  - Histone demethylase Jmjd3 is required for the development of subsets of retinal
      bipolar cells.
AB  - Di- and trimethylation of lysine 27 on histone H3 (H3K27me2/3) is an important
      gene repression mechanism. H3K27me2/3-specific demethylase, Jmjd3, was expressed
      in the inner nuclear layer during late retinal development. In contrast, H3K27
      methyltransferase, Ezh2, was highly expressed in the embryonic retina but its
      expression decreased rapidly after birth. Jmjd3 loss of function in the
      developing retina resulted in failed differentiation of PKC-positive bipolar cell
      subsets (rod-ON-BP) and reduced transcription factor Bhlhb4 expression, which is
      critical for the differentiation of rod-ON-BP cells. Overexpression of Bhlhb4,
      but not of other BP cell-related genes, such as transcription factors Neurod and
      Chx10, in Jmjd3-knockdown retina rescued loss of PKC-positive BP cells.
      Populations of other retinal cell subsets were not significantly affected. In
      addition, proliferation activity and apoptotic cell number during retinal
      development were not affected by the loss of Jmjd3. Levels of histone H3
      trimethyl Lys27 (H3K27me3) in the Bhlhb4 locus were lower in Islet-1-positive BP
      cells and amacrine cells than in the Islet-1-negative cell fraction. The Islet-1
      negative cell fraction consisted mainly of photoreceptors, suggestive of lineage
      specific demethylation of H3K27me3 in the Bhlhb4 locus. We propose that lineage
      specific H3K27me3 demethylation of critical gene loci by spatiotemporal-specific
      Jmjd3 expression is required for appropriate maturation of retinal cells. 

PMID- 24572573
TI  - Mapping the innate signaling cascade essential for cytokine storm during
      influenza virus infection.
AB  - During pathogenic influenza virus infection, robust cytokine production (cytokine
      storm), excessive inflammatory infiltrates, and virus-induced tissue destruction
      all contribute to morbidity and mortality. Earlier we reported that modulation of
      sphingosine-1-phosphate-1 receptor (S1P1R) signaling provided a chemically
      tractable approach for the effective blunting of cytokine storm, leading to the
      improvement of clinical and survival outcomes. Here, we show that S1P1R agonist
      treatment suppresses global cytokine amplification. Importantly, S1P1R agonist
      treatment was able to blunt cytokine/chemokine production and innate immune cell
      recruitment in the lung independently of endosomal and cytosolic innate sensing
      pathways. S1P1R signaling suppression of cytokine amplification was independent
      of multiple innate signaling adaptor pathways for myeloid differentiation primary
      response gene 88 (MyD88) and IFN-beta promoter stimulator-1 signaling, indicating
      a common pathway inhibition of cytokine storm. We identify the MyD88 adaptor
      molecule as responsible for the majority of cytokine amplification observed
      following influenza virus challenge. 

PMID- 24572576
TI  - Concerns over the origin of NIH-CQV, a novel virus discovered in Chinese patients
      with seronegative hepatitis.

PMID- 24572577
TI  - [Epigenetics in the therapy of psychiatric disorders].

PMID- 24572574
TI  - Selective treatment and monitoring of disseminated cancer micrometastases in vivo
      using dual-function, activatable immunoconjugates.
AB  - Drug-resistant micrometastases that escape standard therapies often go undetected
      until the emergence of lethal recurrent disease. Here, we show that it is
      possible to treat microscopic tumors selectively using an activatable
      immunoconjugate. The immunoconjugate is composed of self-quenching, near-infrared
      chromophores loaded onto a cancer cell-targeting antibody. Chromophore
      phototoxicity and fluorescence are activated by lysosomal proteolysis, and light,
      after cancer cell internalization, enabling tumor-confined photocytotoxicity and
      resolution of individual micrometastases. This unique approach not only
      introduces a therapeutic strategy to help destroy residual drug-resistant cells
      but also provides a sensitive imaging method to monitor micrometastatic disease
      in common sites of recurrence. Using fluorescence microendoscopy to monitor
      immunoconjugate activation and micrometastatic disease, we demonstrate these
      concepts of "tumor-targeted, activatable photoimmunotherapy" in a mouse model of
      peritoneal carcinomatosis. By introducing targeted activation to enhance tumor
      selectively in complex anatomical sites, this study offers prospects for catching
      early recurrent micrometastases and for treating occult disease. 

PMID- 24572578
TI  - Neuroimaging procedures and related acquisitions in bipolar disorder: state of
      the art.
AB  - Bipolar disorder (BD) is a chronic and disabling mood disorder, with significant
      suicide rates among psychiatric disorders. Although the pathophysiological bases
      of BD have not been fully elucidated yet, over the last two decades, neuroimaging
      research has documented specific neuroanatomic and functional abnormalities in
      bipolar patients. The present review was aimed to provide an updated and
      comprehensive overview about currently available evidence on main structural and
      functional alterations documented in BD by neuroimaging procedures, through a
      Medline research. Among the structural alterations, the most consistent ones seem
      to be at the level of frontal, temporal and insular cortices, amygdala and basal
      ganglia, having been ventriculomegaly reported as well. Magnetic resonance
      spectroscopy findings showed, in turn, biochemical alterations in several
      neurotransmitter systems. Functional neuroimaging data are quite heterogeneous
      with positron emission tomography and single photon emission computed tomography
      studies showing phase-specific abnormalities of blood flow and glucose
      metabolism, as well as modifications of serotonin transporter density and
      binding. Functional magnetic resonance imaging data documented impaired neural
      networks involved in emotional regulation, including anterior limbic, ventral and
      dorsal prefrontal regions. Taken as a whole, neuroimaging data are strongly
      advancing the understanding of the neural bases of BD as described in the present
      review.

PMID- 24572579
TI  - [Lithium treatment and potential long-term side effects: a systematic review of
      the literature].
AB  - INTRODUCTION AND AIM: Lithium is recommended by all treatment guidelines for
      bipolar disorder (BD) as a first-line maintenance treatment. However, the
      potential side effects and risks associated with long-term lithium use may at
      times make the implementation of these recommendations in daily practice
      challenging. The aim of the study is to review available literature on potential
      long-term side effects of lithium. MATERIALS AND METHODS: A PubMed/Medline search
      was performed on papers dealing with long-term treatment with lithium and side
      effects. Articles published from January 1980 to February 2013 were selected.
      RESULTS: Long-term lithium treatment is associated with a reduced urinary
      concentrating ability, with subsequent polyuria and polidypsia and nephrogenic
      diabetes insipidus (in 10-40% of patients). Lithium also reduces glomerular
      filtration rate, and increases risk of renal failure, although the absolute risk
      is small (0.5% of patients). Lithium treatment is associated with significant
      higher TSH levels, with a 6-fold greater risk of hypothyroidism in lithium
      treated than in control subjects. Less known is the increase of PTH and calcium
      levels induced by lithium. An exacerbation of psoriasis is also frequently
      associated with lithium treatment. CONCLUSIONS: Lithium remains a fundamental
      tool for the treatment of BD. Clinicians should know potential side effects
      (renal, endocrine and dermatological) associated with long-term treatment with
      lithium, for a correct management of the patient. A specialist referral is often
      necessary; the question is how to deal with long-term side effects more than
      whether or not withdrawing lithium. This decision should remain a psychiatrist's
      competence.

PMID- 24572580
TI  - [Comorbidity of hysterical pathologies associated with gynecological diseases:
      historical perspectives and current evidence].
AB  - BACKGROUND: In spite of a large amount of observations made in Psychiatric Day
      Hospital of Sapienza University of Rome relating to comorbidity between sexual
      and gynecological disorders and hysteria, we have attempted to quantify the
      incidence of this phenomenon in order to assess their significance. METHODS: A
      retrospective study was conducted on medical records of patients hospitalized at
      the Day-Hospital of the Policlinico Umberto I in Rome between 1989 and 2009.
      RESULTS: It seems to be confirmed the hypothesis of a high frequency of
      correlating these disorders, although the results lead to a number of critical
      reflections on its significance and the method adopted. CONCLUSIONS: This
      research needs larger and more accurate future investigations, cause the type of
      study was made without direct information.

PMID- 24572581
TI  - [Efficacy of short-term psychodynamic psychotherapy vs treatment as usual in a
      sample of patients with anxiety and depressive disorders].
AB  - INTRODUCTION: The aim of this study is to evaluate the clinical efficacy of short
      term psychodynamic psychotherapy (STPP) in comparison with treatment as usual
      (TAU) in treatment of patients suffering from anxiety and depressive disorders.
      METHODS: Sixty patients were recruited from the Psychotherapy Service, University
      of Milan, Department of Psychiatry, at Milan's IRCCS Foundation Ca' Granda,
      Ospedale Maggiore Policlinico with the diagnosis of depressive or anxiety
      disorders according to DSM-IV-TR criteria. These subjects were randomly assigned
      in a 1:1 ratio to an intervention group (STPP) or control group (TAU) for 12
      months (T1). Each patient was clinically evaluated at the moment of recruitment
      (T0) and after 12 months using a battery composed of these scales: Clinical
      Global Impression Scale (CGI), Symptom Checklist-90-Revised (SCL-90-R), Inventory
      of Interpersonal Problems (IIP). RESULTS: Statistical analysis highlighted
      significant improvements (p<0.05) for the group treated with STPP in every
      clinical scale. Instead control group revealed significant changes (p<0.05) only
      for SCL-90 scale scores. We noticed a clinical improvement in both groups without
      particular differences, but the IIP scores went through a significant higher
      enhancement only in STPP group. CONCLUSIONS: Our results suggest that STPP is so
      effective as TAU in treatment of anxiety and depressive disorders. Moreover STPP
      leads to a better recover of relational functioning.

PMID- 24572582
TI  - Increase in mortality rate in patients with dementia treated with atypical
      antipsychotics: a cohort study in outpatients in Central Italy.
AB  - BACKGROUND: The purpose of this study was to investigate the risk of death among
      elderly outpatients (>65 years) with a dementia diagnosis treated with atypical
      antipsychotics. METHODS: We conducted a cohort study of 696 patients who entered
      the Unit of Alzheimer Evaluation (UVA) of Teramo Hospital in Central Italy,
      during a 3-year period (January 2007-December 2009). Among these patients, 375
      were treated with atypical antipsychotics (quetiapine, risperidone and
      olanzapine). Data were collected from record files sent to the pharmaceutical
      service of the hospital. RESULTS: Patients taking atypical antipsychotic
      medication were associated with a significantly higher mortality rate than
      patients not taking antipsychotics. The relative risk of death in patients
      treated with antipsychotics compared to control patients was 2.354 (95% CI 1.704
      3.279). The greatest increases in mortality rate occurred close to the last drug
      supply, and declined exponentially as time passed from the last drug supply in
      patients who stopped drug assumption. Quetiapine was the most commonly prescribed
      drug and higher doses of this drug were associated with higher mortality rates.
      CONCLUSIONS: These results are in line with the April 2005 warning of the Food
      and Drug Administration (FDA) that among elderly patients with dementia, the
      treatment of behavioural disorders with atypical antipsychotics is associated
      with a higher mortality rate. Given the potential risks of mortality with
      antipsychotics, and since antipsychotic medications may benefit only a minority
      of patients, new approaches are clearly needed to manage the neuropsychiatric
      symptoms of dementia.

PMID- 24572583
TI  - Long-term outcome of schizoaffective disorder. Are there any differences with
      respect to schizophrenia?
AB  - BACKGROUND: A number of studies suggest that the clinical characteristics and
      long-term outcome of schizoaffective patients closely resemble those observed in
      schizophrenia when cases are diagnosed according to DSM criteria. The primary aim
      was to compare remission and recovery rates in a cohort of chronic
      schizoaffective and schizophrenic outpatients. METHODS: A sample of 102
      consecutive outpatients, 46 affected by schizophrenia (45.1%, mean age 44.22+/
      9.97 years) and 66 affected by schizoaffective disorder (54.9%, mean age 43.00+/
      9.07 years) was examined in the study. Personal data and psychiatric history were
      collected according to AMDP system; premorbid assessment was performed by means
      of PAS. Axis I and II psychiatric diagnosis was confirmed by means of SCID-I and
      II. Psychopathological status was evaluated by means of PANSS and CGI-SCH scales;
      neuropsychological evaluation was performed by means of BACS and MMSE;
      Functioning, subjective well-being and quality of life were respectively
      evaluated by means of PSP, SWN and WHOQoL-bref. RESULTS: Schizophrenic and
      schizoaffective patients investigated were characterized by an overlapping age at
      onset, mean duration of illness, mean duration of untreated psychosis and common
      sociodemographic characteristics; subjects' cross-sectional psychopathological
      and neurocognitive profiles were remarkably similar. However, schizoaffective
      patients are more frequently of the female gender, showing a better social
      premorbid adjustment and a somewhat more complicated clinical course in terms of
      more frequent hospitalizations and suicidality; outcome measures are
      substantially better among schizoaffective patients: rates of clinical remission
      were 43.5% and 54.5% in schizophrenic and schizoaffective patients, respectively;
      13% and 25.8% of schizophrenic and schizoaffective patients, respectively, were
      considered as functionally remitted; recovery was observed in 6.5% and 22.7% of
      schizophrenic and schizoaffective patients, respectively; the majority of
      patients, both schizophrenic and schizoaffective, were taking antipsychotics,
      mainly atypical, although a significantly higher proportion of schizoaffective
      subjects were on mood stabilizers, antidepressants and benzodiazepines.
      CONCLUSION: Compared to schizophrenic patients, DSM-IV-TR schizoaffective
      patients may be considered as a subgroup of psychotic patients displaying several
      specific characteristics in terms of clinical course, clinical and functional
      outcome and treatment.

PMID- 24572584
TI  - [Can psychiatric trainees have a role in the improvement of training? The first
      20 years of European Federation of Psychiatric Trainees].
AB  - AIMS: The European Federation of Psychiatric Trainees (EFPT), founded in London
      in 1992, is an independent international federation of psychiatric trainees'
      national associations. The EFPT is engaged in several actions in order to pursue
      its general aims to promote high standards of quality of psychiatric training and
      promote the collaboration and networking between European psychiatric trainees.
      METHODS: Member associations constitute the general assembly that meets annually
      during the European Forum of Psychiatric Trainees. During the Forum, working
      groups are created and the activities for the next year are planned. RESULTS:
      Regular activities of the EFPT include the production of statements expressing
      the standpoint of trainees on educational issues, the conduction of research
      projects, the creation of new national trainees' associations, the facilitation
      of networking among European psychiatric trainees and the organization an annual
      meeting (EFPT Forum). The last EFPT Forum has been organized in Sorrento (Italy)
      on May 2012. Psychiatric trainees from 37 European countries have registered to
      this event. DISCUSSION: EFPT activities constitute a opportunity for psychiatric
      trainees to directly participate in the improvement of their psychiatric training
      and to establish a network with European colleagues that will contribute to their
      professonal development.

PMID- 24572585
TI  - Immediate and short-term use of tolvaptan for acute decompensated heart failure.

PMID- 24572586
TI  - Endothelial progenitor cells in morbid obesity.
AB  - BACKGROUND:  The aim of this study was to assess the relationship among
      anthropometric indexes of adiposity (body mass index [BMI], waist circumference
      [WC]), endothelial progenitor cells (EPC) and carotid intima-media thickness
      (IMT) in patients with morbid obesity, and the effect of diabetes and weight
      loss. METHODS AND RESULTS:  BMI, WC, IMT and circulating EPC (defined as
      CD34+/KDR+/CD45- cells) were assessed in 100 patients (37 with diabetes). Fifty
      patients underwent bariatric surgery, and in 48 of them a complete re-assessment
      after an average follow-up of 252+/-108 days was carried out. In 29 of them
      subcutaneous and visceral adipose tissue samples were obtained at the time of
      intervention and analyzed for the presence and number of EPC. EPC were directly
      correlated with weight, BMI, WC and insulin level, and inversely with mean IMT.
      All correlations were confined to non-diabetic patients. EPC were found in both
      subcutaneous and visceral adipose tissue specimens. Circulating EPC significantly
      decreased after weight loss (P=0.002). CONCLUSIONS:  EPC are positively related
      to markers of adiposity in severe obesity, when not complicated by diabetes.
      Weight loss is associated with decrease in EPC level. EPC are inversely
      correlated with IMT, confirming their protective role also in severe obesity.
      Diabetes has a negative modulating action. 

PMID- 24572587
TI  - Stabilizing effect of small concentrations of PAMAM dendrimers at the insulin
      aggregation.
AB  - Dendrimers' action on proteins and peptides has a dual and controversial
      character. On one hand, they dissolve prion protein and amyloid fibrils
      aggregates, which are otherwise only soluble in solvents containing both
      detergents and high denaturant concentrations. On the other hand they are able to
      destabilize proteins in generation dependent manner. In present work we estimated
      the influence of small concentrations (up to 1.4 MUg/ml) of cationic, neutral and
      anionic poly(amidoamine) dendrimers of 3rd and 4th generations on dithiotreitol
      induced aggregation of insulin. It was found that cationic dendrimers decreased
      the insulin aggregation, while anionic and neutral ones did not. At the same
      time, destabilizing effect of dendrimers on insulin structure was not observed.
      The conclusion was made that small concentrations of dendrimers can be applied to
      prevent or decrease the formation of misfolded structures of protein.

PMID- 24572588
TI  - Infective endocarditis in northeastern Thailand.
AB  - Despite rigorous diagnostic testing, the cause of infective endocarditis was
      identified for just 60 (45.5%) of 132 patients admitted to hospitals in Khon
      Kaen, Thailand, during January 2010-July 2012. Most pathogens identified were
      Viridans streptococci and zoonotic bacteria species, as found in other resource
      limited countries where underlying rheumatic heart disease is common. 

PMID- 24572589
TI  - Novel and functional ABCB1 gene variant in sporadic Parkinson's disease.
AB  - Parkinson's disease (PD) is a common progressive neurodegenerative disease. Most
      cases of PD are sporadic, which is caused by interaction of genetic and
      environmental factors. To date, genetic causes for sporadic PD remain largely
      unknown. ATP-binding cassette sub-family B member 1 (ABCB1) is a membrane
      associated protein that acts as an efflux transporter for many substrates,
      including chemotherapeutic agents, anti-epilepsy medicine, antibiotics and drugs
      for PD. ABCB1 gene is widely expressed in human tissues, including endothelial
      cells of capillary blood vessels at blood-brain barrier sites. In PD patients,
      decreased ABCB1 levels have been reported. We speculated that misregulation of
      ABCB1 gene expression, caused by DNA sequence variants (DSVs) within its
      regulatory regions, may be involved in PD development. In this study, we
      genetically and functionally analyzed the proximal promoter of the human ABCB1
      gene, which is required for constitutive expression, in sporadic PD patients and
      healthy controls. The results showed that a novel and heterozygous DSV
      g.117077G>A was identified in one PD patient, but in none of the controls. This
      DSV significantly altered the transcriptional activity of the ABCB1 gene promoter
      in transiently transfected HEK-293 cells. A heterozygous DSV g.116347T>C was only
      found in one control. Four single-nucleotide polymorphisms, g.116154T>C
      (rs28746504), g.117130A>G (rs2188524), g.117356C>G (rs34976462) and g.117372T>C
      (rs3213619), and one heterozygous deletion DSV g.116039del were found in PD
      patients and controls with similar frequencies. Therefore, our findings suggest
      that ABCB1 gene promoter DSVs may contribute to PD development as a rare risk
      factor. 

PMID- 24572590
TI  - Long term habitual exercise is associated with lower resting level of serum BDNF.
AB  - This experiment has been designed to evaluate the basal serum BDNF level and
      memory performance, and also the change in BDNF in response to acute aerobic and
      anaerobic training in athletes and sedentary groups. Nineteen middle aged elite
      athletes (45-65 years) who used to be competing at domestic championship for more
      than 10 years and 20 sedentary subjects participated in this study. Blood samples
      and cognitive function were assessed at rest and also after performing a single
      bout of acute aerobic and anaerobic exercise. Basal serum BDNF significantly was
      lower in the athletes group compared to the control one (475.18+/-45.32,
      1089.30+/-94.92, P=0.001). Serum BDNF was inversely correlated with Vo2 max (r=
      0.5, P=0.013), but positively with BMI (r=0.2, p=0.4). Pictures recall memory was
      better in the athlete group (9.25+/-1.61) compared with the control ones (8+/
      1.15, p=0.04). Basal platelets did not show any significant differences between
      athletes and controls (p>0.05). Both acute aerobic and anaerobic activity
      elevated serum BDNF and platelets in athletes and sedentary groups compared with
      rest (P<0.001). This study suggests that long-term habitual exercise is
      associated with lower peripheral BDNF and better intermediate memory. However
      acute form of intensive activity either aerobic or anaerobic are capable to
      elevate serum BDNF level in both sedentary and athletes. 

PMID- 24572591
TI  - Effects of L-tryptophan on L-DOPA-induced dyskinesia in the L-methyl-4-phenyl
      1,2,3,6-tetrahydropyridine (MPTP)-treated macaque model of Parkinson's disease.
AB  - In animal models of Parkinson's disease (PD), the serotonergic (5
      hydroxytryptamine, 5-HT) system is thought to play an important
      pathophysiological role in the development and expression of l-3,4
      dihydroxyphenylalanine (l-3,4-dihydroxyphenylalanine-DOPA)-induced dyskinesia
      (LID). These abnormal involuntary movements are associated with the unregulated
      release of dopamine from 5-HT fibres. Thus, modulating the false neurotransmitter
      release from 5-HT neurons, via attuning the serotonin tone, may be a potential
      therapeutic strategy in the treatment of LID. In this study, we investigated the
      effects of the primary precursor of 5-HT, l-tryptophan, on LID in 1-methyl-4
      phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated macaques. l-tryptophan treatment
      (0.5-5.0g) dramatically abolished the expression of LID. However, this effect was
      associated with worsening of the therapeutic effects of L-DOPA. These behavioural
      data further support the role of the serotonergic system in expression of LID,
      highlighting the difficult challenge of targeting 5-HT neurons for alleviating
      dyskinesia and maintaining the therapeutic response of L-DOPA.

PMID- 24572592
TI  - B-vitamins and bone in health and disease: the current evidence.
AB  - Osteoporosis, a metabolic skeletal disease characterised by decreased bone mass
      and increased fracture risk, is a growing public health problem. Among the
      various risk factors for osteoporosis, calcium and vitamin D have well
      established protective roles, but it is likely that other nutritional factors are
      also implicated. This review will explore the emerging evidence supporting a role
      for certain B-vitamins, homocysteine and the 677 C -> T polymorphism in the gene
      encoding the folate-metabolising enzyme methylenetetrahydrofolate reductase, in
      bone health and disease. The evidence, however, is not entirely consistent and as
      yet no clear mechanism has been defined to explain the potential link between B
      vitamins and bone health. Coeliac disease, a common condition of malabsorption,
      induced by gluten ingestion in genetically susceptible individuals, is associated
      with an increased risk both of osteoporosis and inadequate B-vitamin status.
      Given the growing body of evidence linking low bone mineral density and/or
      increased fracture risk with low B-vitamin status and elevated homocysteine,
      optimal B-vitamin status may play an important protective role against
      osteoporosis in coeliac disease; to date, no trial has addressed this possible
      link.

PMID- 24572593
TI  - Does infliximab prevent colectomy in acute and chronic active ulcerative colitis?
AB  - OBJECTIVES: The aim of the study was to evaluate clinical response, use of
      colectomy, and adverse events related to infliximab (IFX) treatment in acute and
      chronic active ulcerative colitis (UC) in children. METHODS: Children from 3
      centers, who had received IFX for UC, were identified, and patient charts were
      reviewed retrospectively. Data concerning symptoms, biochemistry, concomitant
      medical treatment, colectomy, and adverse events were registered. RESULTS: A
      total of 45 patients with UC (median age at diagnosis 12 years, interquartile
      range 10-14) were included, and studied for a median of 15 months (interquartile
      range 4.5-29) after first IFX infusion. The cumulative 1- and 2-year risks of
      colectomy were 21% and 26%, respectively. The cumulative 1- and 2-year risks of
      receiving a new course of systemic corticosteroids were 32% and 48%,
      respectively. Twenty-one patients (46%) experienced adverse events. Most common
      were mild infusion reactions, but 3 (7%) had serious adverse events. CONCLUSIONS:
      IFX was efficient in preventing colectomy in children with UC. The risk of
      receiving systemic corticosteroids was lower than that reported in other studies.
      Most adverse events were mild to moderate and self-limiting.

PMID- 24572594
TI  - Authors' response.

PMID- 24572596
TI  - From the editor.

PMID- 24572597
TI  - Pain management for special populations-pediatric, geriatric, and intensive care
      unit patients.
AB  - The treatment of pain in children, the elderly, and intensive care unit patients
      presents some unique problems. Here a unifying theme is emphasized: the
      difficulty in adequately assessing pain in patients who are often unable to
      communicate. Also addressed are the differences in pharmacokinetics and
      pharmacodynamics from neonates to the elderly. Finally, common pain syndromes in
      each group, the associated treatments, and recent controversies are discussed.
      Because of changing demographics, pain treatment for these groups will become
      increasingly important. Only in the past 10 years has pediatric pain been treated
      with the same energy as adult pain; application of the newest techniques still
      lags far behind these patients' adult counterparts. Pain treatment in the elderly
      will inevitably become a larger problem as our population ages. Finally, recent
      advances in technology enable us to sustain patients with increasingly severe
      illnesses. Thus, pain management in these special populations will take on
      progressively greater importance. 

PMID- 24572599
TI  - Physical examination of the pain patient.

PMID- 24572598
TI  - Myofascial pain and fibromyalgia: Diagnosis and treatment.
AB  - Myofascial pain syndrome (MPS) and fibromyalgia (FM) are common muscular pain
      syndromes. They are both characterized by tenderness, but MPS is further
      characterized by the myofascial trigger point that has a taut band and causes
      referred pain. FM can be either primary (idiopathic) or secondary. MPS is always
      secondary to some muscle stressor. The diagnosis of these conditions is generally
      made by physical examination. Algometry can quantify the tenderness. EMG of the
      trigger point and diagnostic ultrasound can provide objective evidence of the
      trigger point. Biochemical markers and other phenomena associated with FM have
      not yet been shown to be either specific or sensitive enough to use as clinical
      indicators of the condition. Tryptophane is low in the serum and spinal fluid of
      FM patients, whereas substance P is elevated in the spinal fluid. Treatment of
      MPS is effective when the trigger point is inactivated and underlying mechanical
      or medical perpetuating factors are corrected. Treatment of fibromyalgia is more
      difficult as the drugs commonly used, such as the tricyclic antidepressants,
      which have uncertain benefits; and exercise, which clearly shows a short-term
      benefit, fail to provide long-lasting relief at 4 years. 

PMID- 24572600
TI  - Radiofrequency denervation - basic science and clinical application.

PMID- 24572602
TI  - Symposium on osteoporosis: fractures, back pain, disability - management.

PMID- 24572603
TI  - Author indexVolume 11 (1998).

PMID- 24572595
TI  - Characterizing the genetic basis of methylome diversity in histologically normal
      human lung tissue.
AB  - The genetic regulation of the human epigenome is not fully appreciated. Here we
      describe the effects of genetic variants on the DNA methylome in human lung based
      on methylation-quantitative trait loci (meQTL) analyses. We report 34,304 cis-
      and 585 trans-meQTLs, a genetic-epigenetic interaction of surprising magnitude,
      including a regulatory hotspot. These findings are replicated in both breast and
      kidney tissues and show distinct patterns: cis-meQTLs mostly localize to CpG
      sites outside of genes, promoters and CpG islands (CGIs), while trans-meQTLs are
      over-represented in promoter CGIs. meQTL SNPs are enriched in CTCF-binding sites,
      DNaseI hypersensitivity regions and histone marks. Importantly, four of the five
      established lung cancer risk loci in European ancestry are cis-meQTLs and, in
      aggregate, cis-meQTLs are enriched for lung cancer risk in a genome-wide analysis
      of 11,587 subjects. Thus, inherited genetic variation may affect lung
      carcinogenesis by regulating the human methylome. 

PMID- 24572605
TI  - Volume contentsVolume 11 (1998).

PMID- 24572607
TI  - Seroprevalence for Coxiella burnetii, Francisella tularensis, Brucella abortus
      and Brucella melitensis in Austrian adults: a cross-sectional survey among
      military personnel and civilians.
AB  - The prevalence of Coxiella burnetii, Francisella tularensis, Brucella abortus,
      and Brucella melitensis infections in Austria and the exposure risk of military
      personnel were assessed in an exploratory nationwide cross-sectional
      seroprevalence survey in 526 healthy adult individuals, 222 of which were
      soldiers and 304 were civilians. Screening for IgA/IgG antibodies to C. burnetii
      (Phase I) and IgG/IgM antibodies to C. burnetii (Phase II), and to F. tularensis
      was done with commercial enzyme-linked immunosorbent assays. To detect antibodies
      against B. abortus and B. melitensis, an in-house complement fixation test was
      used. Overall, 11 individuals (2.0%) showed antibodies to C. burnetii, 3
      individuals (0.5%) were seropositive for F. tularensis, and one (0.3%) individual
      was borderline positive. All individuals positive or borderline for F. tularensis
      tested negative for antibodies against C. burnetii. All individuals tested
      negative for antibodies against B. melitensis/B. abortus. There were no
      significant differences between the seroprevalence of C. burnetii and F.
      tularensis among military personnel and civilians. Our data demonstrate
      serological evidence of a low rate of exposure to C. burnetii and F. tularensis
      among the Austrian adult population and military personnel. 

PMID- 24572608
TI  - Identification and partial characterization of a Salp15 homolog from Ixodes
      ricinus.
AB  - The immunomodulatory molecule Salp15 is originally described in Ixodes scapularis
      and has been shown to inhibit CD4 T cell activation. Many Salp15 homologs have
      been described from Ixodes species, and all were well conserved at C-terminal
      residues that seem to be essential for the function of the protein. In this
      study, a gene sequence was amplified from cDNA isolated from engorged female I.
      ricinus ticks, which was predicted to generate a protein of 12.3 kDa. The protein
      displayed distinct amino acid differences from previously described I. ricinus
      Salp15 homologs, with amino acid identity ranging between 46.6% and 93.9%. It was
      referred to as I. ricinus Salp15-like protein. The protein showed 48.1% sequence
      identity to I. scapularis Salp15. We analyzed the effect of the recombinant I.
      ricinus Salp15-like protein on the production of cytokines from human peripheral
      blood mononuclear cells stimulated with LPS. The recombinant protein exerted no
      effect on the production of TNF-alpha and IL-6, but the production of IL-10 was
      dose-dependently reduced. It can be concluded that I. ricinus Salp15-like protein
      exerts an immunomodulatory effect on the host. The inhibition of IL-10 production
      may possibly lead to a retardation of B cell activity.

PMID- 24572609
TI  - PCR detection of Babesia ovata from questing ticks in Japan.
AB  - Babesia ovata is a tick-transmitted hemoprotozoan parasite of cattle. In the
      present study, we analyzed tick DNA samples (n=1459) prepared from questing ticks
      collected from various cattle pastures in Hokkaido (Shibecha, Taiki, Otofuke,
      Memuro, and Shin-Hidaka districts) and Okinawa (Yonaguni Island) prefectures of
      Japan for B. ovata. When all the tick DNA samples were screened by a previously
      described B. ovata-specific apical membrane antigen-1 (AMA-1) gene-based
      polymerase chain reaction (PCR) assay, none of the DNA samples was positive.
      Therefore, we developed a PCR assay based on the protozoan beta-tubulin (beta
      tubulin) gene to detect B. ovata from ticks in Japan. In the specificity test,
      the PCR assay amplified the expected 444-bp target gene fragment from B. ovata
      DNA. No PCR products were amplified from DNA samples from other blood pathogens,
      bovine blood, or ticks. In addition, the PCR assay detected 100 fg of B. ovata
      genomic DNA extracted from an in vitro culture of the parasites. Subsequently,
      when all the tick DNA samples were screened by this new PCR assay, 18 were
      positive for B. ovata. Positive samples were found only in the Yonaguni and
      Memuro areas. In Okinawa, where all the ticks were identified as Haemaphysalis
      longicornis, 9.7% of the samples were PCR-positive, while a single tick (Ixodes
      ovatus) from Memuro was infected with B. ovata. When the nucleotide sequences of
      the PCR amplicons were phylogenetically analyzed, they formed a separate clade
      containing a previously described beta-tubulin gene sequence from B. ovata
      (Miyake strain), confirming that the PCR assay had detected only B. ovata from
      the tick DNA samples. This is the first report that describes the PCR detection
      of B. ovata in ticks. The findings warrant transmission experiments to evaluate
      I. ovatus as a potential vector of B. ovata.

PMID- 24572611
TI  - Histoplasmosis associated with a bamboo bonfire--Arkansas, October 2011.
AB  - On October 27, 2011, the Arkansas Department of Health (ADH) was notified by a
      northeast Arkansas primary care provider of a cluster of three histoplasmosis
      cases. On November 4, ADH was notified by a pediatric infectious diseases
      specialist regarding seven potential cases of pulmonary histoplasmosis associated
      with a family gathering that included a bonfire that burned bamboo from a grove
      that had been a red-winged blackbird roost. These reports prompted an outbreak
      investigation to ensure that the persons involved received appropriate medical
      care, to identify whether any novel exposures were associated with illness, and
      to determine whether any factors were associated with hospitalization. The
      investigation found that, among the 19 attendees at the family gathering, seven
      were confirmed with histoplasmosis, 11 were probable, and one did not have
      histoplasmosis. 

PMID- 24572610
TI  - Cryptosporidium parvum IId family: clonal population and dispersal from Western
      Asia to other geographical regions.
AB  - In this study, 111 Cryptosporidium parvum IId isolates from several species of
      animals in China, Sweden, and Egypt were subtyped by multilocus sequence typing
      (MLST). One to eleven subtypes were detected at each of the 12 microsatellite,
      minisatellite, and single nucleotide polymorphism (SNP) loci, forming 25 MLST
      subtypes. Host-adaptation and significant geographical segregation were both
      observed in the MLST subtypes. A clonal population structure was seen in C.
      parvum IId isolates from China and Sweden. Three ancestral lineages and the same
      RPGR sequence were shared by these isolates examined. Therefore, the present
      genetic observations including the higher nucleotide diversity of C. parvum IId
      GP60 sequences in Western Asia, as well as the unique distribution of IId
      subtypes (almost exclusively found in Asia, Europe, and Egypt) and in combination
      with the domestication history of cattle, sheep, and goats, indicated that C.
      parvum IId subtypes were probably dispersed from Western Asia to other
      geographical regions. More population genetic structure studies involving various
      C. parvum subtype families using high-resolution tools are needed to better
      elucidate the origin and dissemination of C. parvum in the world. 

PMID- 24572612
TI  - Multiple-serotype salmonella outbreaks in two state prisons--Arkansas, August
      2012.
AB  - In August 2012, the Arkansas Department of Health (ADH) was notified of
      gastrointestinal illness outbreaks in two Arkansas state prisons. ADH
      investigated the outbreaks and conducted case-control studies to identify the
      source of the illnesses. This report describes the results of these
      investigations, which identified 528 persons with onset of diarrhea during August
      2-18, 2012. Results from the prison A investigation identified chicken salad as
      the most likely vehicle. At prison B, person-to-person transmission and
      contamination of multiple foods likely contributed to illness. Analysis of stool
      specimens from inmates identified eight serotypes and 15 pulsed-field gel
      electrophoresis (PFGE) patterns of Salmonella. Isolates of Salmonella from eggs
      produced at prison B matched two outbreak patterns. An additional 69 inmates were
      positive by culture but were not interviewed or did not report diarrhea, making
      the total case count 597. Sanitarians identified problems with food preparation,
      hand washing, and food safety training. ADH tested inmate kitchen workers,
      excluded infected inmates from work, and provided food safety training. Prison
      kitchen staff should follow guidelines consistent with state regulations for safe
      food preparation and pass sanitarian inspection. 

PMID- 24572613
TI  - Two-dose varicella vaccination coverage among children aged 7 years--six sentinel
      sites, United States, 2006-2012.
AB  - In 2007, the Advisory Committee on Immunization Practices (ACIP) recommended a
      routine second dose of varicella vaccine for children at age 4-6 years, in
      addition to the first dose given at age 12-15 months. One strategy recommended
      for increasing varicella vaccination coverage is a school entry requirement of
      proof of varicella immunity. To determine the extent of implementation of the
      routine 2-dose varicella vaccination program, the number of states with a 2-dose
      varicella vaccination elementary school entry requirement in 2012 was compared
      with the number in 2007, and 2-dose varicella vaccination coverage during 2006
      was compared with coverage in 2012 among children aged 7 years, using data from
      six Immunization Information System (IIS) sentinel sites. The number of states
      (including the District of Columbia) with a 2-dose varicella vaccination
      elementary school entry requirement increased from four in 2007 to 36 in 2012.
      Two-dose varicella vaccination coverage levels among children aged 7 years in the
      six IIS sentinel sites increased from a range of 3.6%-8.9% in 2006 to a range of
      79.9%-92.0% in 2012 and were approaching the levels of 2-dose measles, mumps, and
      rubella (MMR) coverage, which had a range of 81.9%-94.0% in 2012. These increases
      suggest substantial progress in implementing the routine 2-dose varicella
      vaccination program in the first 6 years since its recommendation by ACIP. Wider
      adoption of 2-dose varicella vaccination school entry requirements might help
      progress toward the Healthy People 2020 target of 95% of kindergarten students
      having received 2 doses of varicella vaccine. 

PMID- 24572615
TI  - From the editor.

PMID- 24572616
TI  - Psychological factors in chronic pain: assessment and treatment issues.
AB  - This article presents an overview of psychological factors which influence
      chronic pain. Emphasis is placed on assessment techniques and psychological
      treatment approaches for patients with chronic pain. In the first section, the
      usefulness of psychometric measures are discussed and areas considered critical
      in the psychological assessment of chronic pain are reviewed, including (1) pain
      intensity, (2) functional capacity, (3) mood and personality, (4) pain beliefs
      and coping, (5) medication usage, (6) adverse effects, (7) behavioral analysis,
      and (8) health care utilization. Personality factors affecting pain syndromes,
      DSM-IV diagnoses and health care utilization issues are also discussed. In the
      second section, an overview of psychological and behavioral interventions for
      chronic non-malignant pain are presented within the context of a multi
      disciplinary pain management program. A rationale for a group-based program along
      with roles of a team, program goals, patient selection criterion, components of
      the program, and information on program evaluation is reviewed. 

PMID- 24572614
TI  - Notes from the field: wildlife rabies on an island free from canine rabies for 52
      years--Taiwan, 2013.
AB  - Dog-to-dog transmission of rabies in Taiwan was eliminated in 1961; the island
      was considered canine rabies-free for 52 years. On July 16, 2013, three ferret
      badgers (Melogale moschata) tested positive for rabies by fluorescent antibody
      testing at the Animal Health Research Institute, Council of Agriculture of
      Taiwan. This was the first time wild animals other than bats were tested. During
      1999-2012, a total of 6,841 clinically healthy dogs and five apparently normal
      cats from shelters were tested and found negative for rabies. During 2009-2012, a
      total of 322 bats were tested and found negative for rabies. 

PMID- 24572617
TI  - Measuring outcomes: the key to quality management.
AB  - Managed care continues to encroach upon virtually all health care delivery
      systems. Cost controls within these systems have been governed in the past by
      selection/deselection procedures and utilization management that are primarily
      based upon claims cost data. The recent movement toward integration of health
      care quality measures with financial data offers some hope that quality will not
      be unduly compromised in the efforts to control health care costs. In this new
      milieu there are increasing opportunities for health care professionals to
      participate in the development and refinement of managed care products. A model
      for a worker's compensation managed care system being developed in Colorado is
      offered as an example of the movement toward more meaningful partnering between
      health care payers and providers. 

PMID- 24572618
TI  - A practical approach to pain management in patients with cancer and AIDS.
AB  - This review describes practical management techniques for pain associated with
      cancer and AIDS. Multi-disciplinary and multi-modality approaches are discussed. 

PMID- 24572619
TI  - Injection techniques in the management of local pain.
AB  - This is a review of local anesthetic (LA) injections and infiltrations
      particularly combined with 'needling' for management of local musculoskeletal
      pain. New techniques are described including preinjection blocks (PIBs) which
      consist of blocking the sensory input from an area prior to giving an injection.
      PIBs prevent pain which would be caused by needle penetration of sensitive
      tissue. Needling and infiltration (N and I) with 1% lidocaine has been performed
      after PIB in 179 tender spots (TSs), trigger points (TrPs), and muscle spasms by
      the author, in 123 patients with the goal to relieve pain and promote healing.
      The immediate effect after the procedure as well as long-term results from 1 week
      to 7 months have been evaluated independently by a physiatrist experienced with
      injections (Dr. Tae Mo Chang). N and I extending over the entire taut band of
      abnormal muscle fibers, caused effective relief of pain and functional
      improvement in tender spots (TSs), trigger points (TrPs) and in muscle spasm
      caused by a variety of conditions including: acute and chronic sports and work
      injuries, motor vehicle accidents, muscle and ligament sprains (supraspinous,
      sacroiliac), overuse and repetitive stress syndromes, tennis elbow; local
      injuries or radicular irritation; and local inflammations such as bursitis,
      tendinitis, and osteoarthritis; and traumatic dystrophy, a type of reflex
      sympathetic dystrophy. Needling and infiltration of trigger areas and tender
      spots is effective treatment in several conditions. Pre-injection blocks allow
      the performance of the N and I of tender areas without pain. 

PMID- 24572620
TI  - Pelvic pain.
AB  - This paper focuses on the special aspects of pelvic pain that make it a difficult
      area in which to work. This will be done by use of specific examples of certain
      chronic pelvic pain conditions. This will be followed by a general discussion of
      current diagnosis and treatment methods for common pain syndromes. Most of these
      patients are women who suffer from pelvic pain. Case presentations will be used
      to illustrate the application of the materials presented. In the final analysis,
      diagnosis and management of chronic pelvic pain is best treated by an individual
      who is experienced, knowledgeable, and cognizant of the intricate relationship
      between pain, organopathology and neuropathology. 

PMID- 24572621
TI  - Origins of pain in HIV/AIDS.

PMID- 24572623
TI  - Carl Woese, Dick Young, and the roots of astrobiology.
AB  - The beginning of the space age in the late 1950s gave rise to innovative and
      interdisciplinary research concepts and perspectives, including the concept of
      "exobiology" as a way to approach the fundamental aspects of biology through a
      study of life outside of the Earth, if it existed. This concept was embodied by
      NASA into its formal Exobiology Program and into the philosophy of the program
      both before and after the Viking missions that were launched to Mars to search
      for signs of life in 1975. Due to both management flexibility and an acceptance
      of the interdisciplinary nature of the problem of "life in the universe," NASA
      program managers, and particularly Richard S Young who ran the Exobiology Program
      beginning 1967, have made some excellent investments in paradigm altering science
      of great use both on Earth and on future space missions. The work of Carl Woese
      is one such example, which has revolutionized our understanding of the microbial
      world and the relationships of all life on Earth. 

PMID- 24572624
TI  - Blink reflex recovery cycle distinguishes essential tremor with resting tremor
      from de novo Parkinson's disease: an exploratory study.
AB  - An increased R2 recovery component of the blink reflex (R2-BRrc) has been
      observed in Parkinson's disease (PD), cranio-cervical dystonia, dystonic tremor
      and essential tremor with associated resting tremor (rET), while the BRrc was
      reported normal in patients with essential tremor (ET). Distinguishing rET from
      tremor dominant PD (tPD) may be challenging especially in the first stages of the
      diseases, in the absence of DAT-SPECT investigation. We evaluated the possible
      usefulness of BRrc for differentiating subjects with de novo tPD from those with
      rET. We investigated R2-BRrc at interstimulus intervals (ISI) of 100, 150, 200,
      300, 400, 500 and 750 ms in 11 participants with tPD, 10 with rET and 20 healthy
      controls. All participants underwent DAT-SPECT and cardiac MIBG scintigraphy. R2
      recovery was significantly enhanced in tPD compared to controls at all
      investigated ISIs (p < 0.001), while in subjects with rET patients BRrc was
      significantly increased compared to controls at ISI 150, 200, 300, 400, 500 and
      750 ms (p < 0.001). At ISI 100 R2-BRrc distinguished patients participants with
      de novo tPD from those with rET with a sensitivity, specificity and accuracy of
      100%. Our findings demonstrate the usefulness of BRrc for differentiating de novo
      tPD from rET.

PMID- 24572625
TI  - Acinar cell carcinoma of exocrine pancreas in two horses.
AB  - Two horses were presented with non-specific clinical signs of several weeks'
      duration and were humanely destroyed due to a poor prognosis. At necropsy
      examination, both horses had multiple small, white nodules replacing pancreatic
      tissue and involving the serosal surface of the abdominal cavity, the liver and
      the lung. Microscopically, neoplastic cells were organized in acini and contained
      abundant (case 1) or sparse (horse 2) intracytoplasmic zymogen granules.
      Immunohistochemically, both tumours expressed amylase and pan-cytokeratin, but
      not insulin or neuron-specific enolase. In case 2, a low percentage of neoplastic
      cells expressed glucagon and synaptophysin. The presence of zymogen granules was
      confirmed in both cases by electron microscopy and occasional fibrillary or
      glucagon granules were observed in cases 1 and 2, respectively. A diagnosis of
      pancreatic acinar cell carcinoma was established in both horses. 

PMID- 24572627
TI  - Facile fabrication of corrosion-resistant superhydrophobic and superoleophilic
      surfaces with MnWO(4):Dy(3+) microbouquets.
AB  - Superhydrophobic and superoleophilic MnWO4:Dy(3+) microbouquets were successfully
      fabricated via a facile hydrothermal process. The surface morphologies and
      chemical composition were investigated by scanning electron microscopy (SEM) and
      X-ray powder diffraction (XRD). The wettability of the as-synthesized
      MnWO4:Dy(3+) microbouquet film was studied by measuring the water contact angle
      (CA). A static CA for water of 165 degrees  and a very low sliding angle (SA)
      were observed, which were closely related to both the MnWO4:Dy(3+) microbouquet
      structure and chemical modification. Furthermore, the as-prepared MnWO4:Dy(3+)
      surface showed superhydrophobicity for some corrosive liquids such as aqueous
      basic and salt solutions. 

PMID- 24572626
TI  - Associations of lifetime active and passive smoking with spontaneous abortion,
      stillbirth and tubal ectopic pregnancy: a cross-sectional analysis of historical
      data from the Women's Health Initiative.
AB  - OBJECTIVE: To examine the associations between tobacco exposure and adverse
      pregnancy outcomes using quantitative measures of lifetime active smoking and
      secondhand smoke (SHS) exposure. METHODS: Historical reproductive data on 80 762
      women who participated in the Women's Health Initiative Observational Study were
      examined with a cross-sectional analysis. We assessed self-reported lifetime
      active and passive tobacco smoke exposure, self-reported spontaneous abortions,
      stillbirths and ectopic pregnancies. RESULTS: When compared with never-smoking
      women, participants who were ever active smokers during their reproductive years
      had ORs (OR) of 1.16 (95% CI 1.08 to 1.26) for 1 or more spontaneous abortions,
      1.44 (95% CI 1.20 to 1.73) for 1 or more stillbirths, and 1.43 (95% CI 1.10 to
      1.86) for 1 or more ectopic pregnancies. Never-smoking women participants with
      the highest levels of lifetime SHS exposure, including childhood >10 years, adult
      home >20 years and adult work exposure >10 years, when compared with never
      smoking women with no SHS exposure had adjusted ORs of 1.17 (95% CI 1.05 to 1.30)
      for spontaneous abortion, 1.55 (95% CI 1.21 to 1.97) for stillbirth, and 1.61
      (95% CI 1.16 to 2.24) for ectopic pregnancy. CONCLUSIONS: Women who were ever
      smokers during their reproductive years had significantly greater estimates of
      risk for spontaneous abortion, stillbirth and tubal ectopic pregnancy. Never
      smoking women with the highest levels of lifetime exposure to SHS had
      significantly increased estimates of risk for spontaneous abortion, stillbirth
      and tubal ectopic pregnancy.

PMID- 24572628
TI  - An overview on mycotoxin contamination of foods in Africa.
AB  - Mycotoxins are fungal secondary metabolites that contaminate various feedstuffs
      and agricultural crops. The contamination of food by mycotoxins can occur before
      production, during storage, processing, transportation or marketing of the food
      products. High temperature, moisture content and water activity are among the
      predisposing factors that facilitate the production of mycotoxins in food.
      Aflatoxins, ochratoxins, fumonisins, deoxynivalenol and zearalenone are all
      considered the major mycotoxins produced in food and feedstuffs. In Africa,
      mycotoxin contamination is considered to be a major problem with implications
      that affect human and animal health and economy. Aflatoxin-related hepatic
      diseases are reported in many African countries. Ochratoxin and fumonisin
      toxicity in humans and animals is widespread in Africa. The available, updated
      information on the incidence of mycotoxin contamination, decontamination and its
      public health importance in Africa is lacking. The aim of this review is to
      highlight, update and discuss the available information on the incidence of
      mycotoxins in African countries. The public health implications and the
      recommended strategies for control of mycotoxins in food and agricultural crops
      are also discussed. 

PMID- 24572629
TI  - Cerebellar ataxia suspected to be caused by Oxytropis glabra poisoning in western
      Mongolian goats.
AB  - In the last five years in western Mongolia, a neurological disorder and resultant
      economic loss have developed in goats, sheep, cattle and horses: association of
      the disease with ingestion of Oxytropis glabra, a toxic plant, was suggested.
      Affected goats showed neurological signs, including ataxia, incoordination, hind
      limb paresis, fine head tremor and nystagmus. Three goats, one with moderate
      clinical signs and the other two with severe clinical signs, were necropsied and
      examined to describe and characterize the histologic, immunohistochemical and
      ultrastructural lesions. Although no gross pathological changes were observed in
      a variety of organs including the central nervous system of these goats,
      microscopic examination of the cerebellum demonstrated degenerative changes in
      all these goats, such as vacuolar changes and loss of Purkinje cells, torpedo
      formation in the granular layer, increased number of spheroids in the cerebellar
      medulla, and loss of axons and myelin sheaths of Purkinje cells. The chemical
      analysis of the dried plant detected 0.02-0.05% (dry weight basis) of
      swainsonine. This is the first report describing the clinical and pathological
      findings in Mongolian goats suspected to be affected by O. glabra poisoning. 

PMID- 24572630
TI  - Peculiar composition of epithelial cells in follicle-associated intestinal crypts
      of Peyer's patches in the rat small intestine.
AB  - The epithelial cell composition was investigated in the follicle-associated
      intestinal crypt (FAIC) of rat Peyer's patches. The epithelium of the FAIC mainly
      consisted of columnar epithelial cells, goblet cells and Paneth cells. The
      characteristics of secretory granules in Paneth cells and goblet cells of both
      the FAIC and ordinary intestinal crypts (IC) were almost the same in periodic
      acid-Schiff (PAS) reaction, Alcian blue (AB) staining and the immunohistochemical
      detection of lysozymes and soluble phospholipase A2. Both goblet cells and Paneth
      cells were markedly less frequent on the follicular sides than on the anti
      follicular sides of the FAIC. Goblet cells were also markedly less frequent in
      the follicle-associated epithelium (FAE) than in the ordinary intestinal villi
      (IV). Indigenous bacteria were more frequently adhered to FAE than to follicle
      associated intestinal villi or IV. These findings suggest that the host defense
      against indigenous bacteria is inhibited on the follicular sides of FAIC, which
      might contribute to the preferential settlement of indigenous bacteria on the
      FAE; they also suggest that differentiation into secretory cells is inhibited in
      the epithelium of the follicular sides of FAIC, so that differentiation into M
      cells might be admitted in the FAE of rat Peyer's patches. Furthermore,
      intermediate cells possessing characteristics of both Paneth cells and goblet
      cells were rarely found in the FAIC, but not in the IC. This finding suggests
      that the manner of differentiation into Paneth cells in the FAIC differs from
      that in the IC. 

PMID- 24572631
TI  - Effects of lidocaine, dexmedetomidine or their combination on the minimum
      alveolar concentration of sevoflurane in dogs.
AB  - The aim of this study was to determine the effects of lidocaine (LIDO) and
      dexmedetomidine (DEX) or their combination (LIDO-DEX), administered by constant
      rate infusion (CRI), on the minimum alveolar concentration (MAC) of sevoflurane
      in dogs. Seven healthy mongrel dogs were used with a 2-week washout interval
      between treatments in this study. Anesthesia was induced with propofol and
      maintained with sevoflurane in oxygen, and MAC of sevoflurane was determined
      after 90 min equilibration period in the dogs (SEV-MACBASAL). Then, sevoflurane
      MAC was determined again in the dogs after 45 min equilibration period of one of
      the following treatments: an intravenous loading dose of lidocaine 2 mg/kg
      followed by 6 mg/kg/hr CRI (SEV-MACLIDO); an intravenous loading dose of
      dexmedetomidine 2 ug/kg followed by 2 ug/kg/hr CRI (SEV-MACDEX); or their
      combination (SEV-MACLIDO-DEX). These SEV-MACs were determined in duplicate. Data
      were analyzed using ANOVA and post hoc Tuckey test when appropriate. The SEV
      MACBASAL was 1.82 +/- 0.06%, SEV-MACLIDO was 1.38 +/- 0.08%, SEV-MACDEX was 1.22
      +/- 0.10%, and SEV-MACLIDO-DEX was 0.78 +/- 0.06%. The CRI administration of
      lidocaine, dexmedetomidine and their combination produced a significant reduction
      in the MAC of sevoflurane by 26.1 +/- 9.0% (P<0.0001), 43.7 +/- 11.8% (P<0.0002)
      and 54.4 +/- 9.8% (P<0.0001), respectively. The MAC reduction was significantly
      greater after the CRI combination of lidocaine and dexmedetomidine when compared
      with lidocaine CRI (P<0.0001) or dexmedetomidine CRI treatments (P<0.025). 

PMID- 24572632
TI  - Influence of atopic dermatitis on reproduction and uterine natural killer cells.
AB  - The causal relationship between severe allergic conditions and successful
      pregnancy remains unclear. We aimed to evaluate reproductive performance in an
      experimental mouse model of atopic disease (AD), and the appearance of uterine
      natural killer (uNK) cells that have crucial roles in placental formation was
      examined. In the NC/Nga pregnant mice with moderate skin allergic lesions and an
      8.6-fold elevation of plasma IgE, significant differences were not detected in
      the reproductive indices of the number of normal fetuses, abortion rate and
      placental size. There were few uNK cells in the placenta of AD mice, and they
      showed a significant decrease regarding the immature subtype as compared with
      controls. These findings revealed that AD disturbs uNK cell differentiation and
      provides disadvantageous effects on placental formation, although it does not
      arrest the pregnancy process. It may be possible that specific immunological
      conditions behind AD operate favorably to recover the reproductive performance. 

PMID- 24572633
TI  - Cystic rete ovarii and uterine tube adenoma in a rabbit.
AB  - A 6-year-old female rabbit was presented to a veterinary clinic, and the result
      of ultrasound examination suggested a tumor in the uterine tube. Subsequently,
      both ovaries and uterus were surgically removed. In gross, a single large cyst in
      the right ovary and enlargement of the left uterine tube were observed.
      Histological examination revealed that the cyst had developed in the hilus of the
      ovary and was lined by single-layered cuboidal cells. In the left uterine tube, a
      tumor composed of epithelial cells arranged in tubular structures and pleomorphic
      cells between the tubular structures was observed. Immunohistochemically, the
      epithelial cells of the cyst were positive for pan-cytokeratin, cytokeratin 18,
      CD10, E-cadherin, calretinin and estrogen receptor; the tumor cells of the left
      uterine tube were positive for pan-cytokeratin, cytokeratin 18, E-cadherin,
      vimentin, calretinin and estrogen receptor. From these results, the cyst was
      diagnosed as cystic rete ovarii, and the tumor was diagnosed as adenoma of the
      uterine tube. This case is the first to demonstrate cystic rete ovarii and
      uterine tube adenoma in rabbits. 

PMID- 24572636
TI  - Adaptive real-time dual-comb spectroscopy.
AB  - The spectrum of a laser frequency comb consists of several hundred thousand
      equally spaced lines over a broad spectral bandwidth. Such frequency combs have
      revolutionized optical frequency metrology and they now hold much promise for
      significant advances in a growing number of applications including molecular
      spectroscopy. Despite an intriguing potential for the measurement of molecular
      spectra spanning tens of nanometres within tens of microseconds at Doppler
      limited resolution, the development of dual-comb spectroscopy is hindered by the
      demanding stability requirements of the laser combs. Here we overcome this
      difficulty and experimentally demonstrate a concept of real-time dual-comb
      spectroscopy, which compensates for laser instabilities by electronic signal
      processing. It only uses free-running mode-locked lasers without any phase-lock
      electronics. We record spectra spanning the full bandwidth of near-infrared fibre
      lasers with Doppler-limited line profiles highly suitable for measurements of
      concentrations or line intensities. Our new technique of adaptive dual-comb
      spectroscopy offers a powerful transdisciplinary instrument for analytical
      sciences. 

PMID- 24572638
TI  - Multifunctional Eu3+- and Er3+/Yb3+-doped GdVO4 nanoparticles synthesized by
      reverse micelle method.
AB  - Synthesis of Eu(3+)- and Er(3+)/Yb(3+)-doped GdVO4 nanoparticles in reverse
      micelles and their multifunctional luminescence properties are presented. Using
      cyclohexane, Triton X-100, and n-pentanol as the oil, surfactant, and co
      surfactant, respectively, crystalline nanoparticles with ~4 nm diameter are
      prepared at low temperatures. The particle size assessed using transmission
      electron microscopy is similar to the crystallite size obtained from X-ray
      diffraction measurements, suggesting that each particle comprises a single
      crystallite. Eu(3+)-doped GdVO4 nanoparticles emit red light through
      downconversion upon UV excitation. Er(3+)/Yb(3+)-doped GdVO4 nanoparticles
      exhibit several functions; apart from the downconversion of UV radiation into
      visible green light, they act as upconvertors, transforming near-infrared
      excitation (980 nm) into visible green light. The ratio of green emissions from
      (2)H11/2 -> (2)I15/2 and (4)S3/2 -> (4)I15/2 transitions is temperature dependent
      and can be used for nanoscale temperature sensing with near-infrared excitation.
      The relative sensor sensitivity is 1.11%K(-1), which is among the highest
      sensitivities recorded for upconversion-luminescence-based thermometers. 

PMID- 24572637
TI  - Coxiella burnetii seroprevalence and risk for humans on dairy cattle farms, the
      Netherlands, 2010-2011.
AB  - Q fever, caused by Coxiella burnetii, is a recognized occupational infection in
      persons who have regular contact with ruminants. We determined C. burnetii
      seroprevalence in residents living or working on dairy cattle farms with >=50
      adult cows and identified risk factors for seropositivity. Serum samples from
      farm residents, including employees, were tested for C. burnetii IgG and IgM;
      seroprevalence was 72.1% overall and 87.2%, 54.5%, and 44.2% among farmers,
      spouses, and children, respectively. Risk factors included farm location in
      southern region, larger herd size, farm employment, birds in stable, contact with
      pigs, and indirect contact with rats or mice. Protective factors included
      automatic milking of cows and fully compliant use of gloves during and around
      calving. We recommend strengthening general biosecurity measures, such as
      consistent use of personal protective equipment (e.g., boots, clothing, gloves)
      by farm staff and avoidance of birds and vermin in stables.

PMID- 24572639
TI  - Chronic pain after surgery: pathophysiology, risk factors and prevention.
AB  - Interest in chronic pain after surgery has grown since the finding that more than
      a fifth of patients attending chronic pain clinics cite surgery as the cause for
      their chronic pain. The problem is not limited to major surgery; even common
      minor procedures such as hernia repair have a significant risk of chronic pain.
      Surgical technique can influence the development of chronic postsurgical pain
      (CPSP) and techniques to minimise nerve injury should be used where possible.
      Central nervous system changes contribute to the development of persistent pain
      following surgical trauma and nerve injury. Pharmacological agents that interrupt
      the mechanisms contributing to central sensitisation may be helpful in reducing
      the incidence of CPSP. Psychosocial factors are also important in the development
      of chronic pain and should be addressed as part of a holistic approach to
      perioperative care. 

PMID- 24572640
TI  - Effects of cigarette smoke on Holter ECG recordings in patients with arterial
      hypertension. Part 2: Parameters of heart rate turbulence.
AB  - The studies aimed at evaluation of cigarette smoke effect on heart rate
      turbulence (HRT) in patients with arterial hypertension (AH). 223 consecutive
      individuals were qualified to the studies. The following groups of patients not
      suffering from other disease which may affect HRT were distinguished: 1--patients
      with AH (n=145); 2--patients without AH (n=48). In group 1 the following patient
      subgroups were studied: A--active smokers (n=42), B--non-smokers exposed to
      cigarette smoke (n=30), C--non-smokers not exposed to tobacco smoke (n=34), D-
      former smokers who had quit smoking (n=26). In every participant HRT analysis was
      conducted. Subgroup A manifested significantly higher values of TO and lower
      values of TS as compared to analogous values obtained in subgroups B-D. Subgroups
      B and D were characterized also by significantly higher values of TO and lower
      values of TS as compared to subgroup C. Active and passive cigarette smoking were
      found to represent independent risk factors for an abnormal HRT. CONCLUSION: Both
      active and passive exposure to tobacco smoke induces causes abnormal HRT in
      patients with arterial hypertension.

PMID- 24572642
TI  - Drug consumption rooms and the role of politics and governance in policy
      processes.
AB  - BACKGROUND: In 2012 after more than 20 years of discussion Denmark introduced
      drug consumption facilities as part of its drug policy. This article investigates
      the processes that led to this new policy and its implementation in Copenhagen.
      The aim of the article is to analyze if the new policy and its implementation can
      be understood in terms of a shift from 'government' to 'governance' in drug
      policy. On this basis the aim is also to discuss the possibilities and
      limitations of 'governance' as an analytical perspective for understanding policy
      change in the field of drug policy. METHODS: Through the use of Kingdon's theory
      about policy change as following alignments of problem streams, policy streams
      and politics streams and deployment of Callon's concepts of 'framing' and
      'overflowing' the article presents an analysis of recorded communication from the
      public debate and national and local policy processes. RESULTS: Politics and the
      authority of government played a key role in the policy change that led to the
      introduction of drug consumption facilities in Denmark. It was only after a
      change of government and a change of legislation that a new policy came about.
      Drug consumption facilities did exist on a small scale before this through acts
      of civil disobedience committed by civil society stakeholders. CONCLUSION: The
      space for governance seems to be limited in a drug policy that is prohibitive, at
      least when it touches upon issues that concern law enforcement and the sovereign
      power of the state.

PMID- 24572641
TI  - First report on isolation of methyl gallate with antioxidant, anti-HIV-1 and HIV
      1 enzyme inhibitory activities from a mushroom (Pholiota adiposa).
AB  - In this study, a compound with antioxidant and anti-HIV activities designated as
      HEB was first isolated from the edible mushroom Pholiota adiposa by extraction
      with ethanol and ethyl acetate. HEB was then purified by high performance liquid
      chromatography (HPLC) and identified to be methyl gallate (C8H8O5, 184.1 Da)
      based on data from its mass spectrum (MS) and nuclear magnetic resonance (NMR)
      spectrum. HEB displayed strong antioxidant potency in inhibiting, at 1.36 mM
      concentration, erythrocyte hemolysis and scavenging DPPH radicals and superoxide
      anion (O2(-)) by 82.4%, 85.6% and 71.4%, respectively. Besides exhibiting a low
      cytotoxicity, compound HEB demonstrated significant anti-HIV activity in that it
      inhibited HIV-1 replication in TZM-BL cells infected by pseudovirus with an IC50
      value of 11.9 MUM. Further study disclosed that HEB inhibited the viral entry
      process and activities of key enzymes essential for the HIV-1 life cycle. HEB
      inhibited HIV-1 reverse transcriptase and integrase activities with an IC50 value
      of 80.1 MUM and 228.5 MUM, respectively, and at 10 mM concentration inhibited HIV
      1 protease activity by 17.1% which was higher than that achieved by the positive
      control pepstatin A. Interestingly, this study first revealed that H2O2
      stimulation not only activated cell oxidative stress responses, but also
      accelerated HIV-1 long terminal repeat (LTR) promotion in TZM-BL cells, which was
      significantly reduced by HEB from 18.2% to about 2%. It implied a direct
      relationship between the antioxidant and anti-HIV activities of the natural
      active constituent HEB. Nuclear transcription factor kappa B (NF-kappaB) signal
      pathways plays an important role in oxidative stress responses. Meanwhile, there
      is kappaB target sequence in HIV promoter LTR which is significant for virus
      replication and gene expression. In this study, Western Blot assay showed that
      HEB could inhibit the activation of NF-kappaB signal pathway stimulated by H2O2
      in mouse spleen cells through suppressing NF-kappaB (p65) translocation into
      nucleus and NF-kappa-B inhibitor (IkappaB) degradation in cytoplasm. In summary,
      the antioxidant HEB from P. adiposa could inhibit HIV-1 replication through
      multiple target sites. The data suggest that natural antioxidant compounds might
      have a potential for treatment of AIDS.

PMID- 24572645
TI  - Introduction.

PMID- 24572646
TI  - Introduction to the knee.

PMID- 24572647
TI  - Functional rehabilitation of the knee.

PMID- 24572648
TI  - Patellofentoral dysfunction and overuse syndromes.

PMID- 24572643
TI  - Hand hygiene and risk of influenza virus infections in the community: a
      systematic review and meta-analysis.
AB  - Community-based prevention strategies for seasonal and pandemic influenza are
      essential to minimize their potential threat to public health. Our aim was to
      evaluate the efficacy of hand hygiene interventions in reducing influenza
      transmission in the community and to investigate the possible modifying effects
      of latitude, temperature and humidity on hand hygiene efficacy. We identified 979
      articles in the initial search and 10 randomized controlled trials met our
      inclusion criteria. The combination of hand hygiene with facemasks was found to
      have statistically significant efficacy against laboratory-confirmed influenza
      while hand hygiene alone did not. Our meta-regression model did not identify
      statistically significant effects of latitude, temperature or humidity on the
      efficacy of hand hygiene. Our findings highlight the potential importance of
      interventions that protect against multiple modes of influenza transmission, and
      the modest efficacy of hand hygiene suggests that additional measures besides
      hand hygiene may also be important to control influenza.

PMID- 24572649
TI  - Meniscal injuries.

PMID- 24572650
TI  - Treatment and rehabilitation of cruciate and collateral ligament injuries in the
      knee.

PMID- 24572651
TI  - Knee disorders in the skeletally immature athlete.

PMID- 24572652
TI  - On the value of plain films.

PMID- 24572653
TI  - Research opportunities.
AB  - "Research Opportunities" is a regular feature of the Journal that attempts to
      provide readers with relevant information regarding funding opportunities, policy
      changes, and future initiatives of the major sources of support for basic and
      applied research in spine and musculoskeletal rehabilitation. We welcome reader
      responses and suggestions concerning future topics for this section. This issue's
      section provides a description of the National Center for Medical Rehabilitation
      Research, a newly created unit of the National Institutes of Health, established
      in 1990 to provide leadership in the conduct and support of research in medical
      rehabilitation. 

PMID- 24572654
TI  - Prevention and control of haemophilus influenzae type b disease: recommendations
      of the advisory committee on immunization practices (ACIP).
AB  - This report compiles and summarizes all recommendations from CDC's Advisory
      Committee on Immunization Practices (ACIP) regarding prevention and control of
      Haemophilus influenzae type b (Hib) disease in the United States. As a
      comprehensive summary of previously published recommendations, this report does
      not contain any new recommendations; it is intended for use by clinicians, public
      health officials, vaccination providers, and immunization program personnel as a
      resource. ACIP recommends routine vaccination with a licensed conjugate Hib
      vaccine for infants aged 2 through 6 months (2 or 3 doses, depending on vaccine
      product) with a booster dose at age 12 through 15 months. ACIP also recommends
      vaccination for certain persons at increased risk for Hib disease (i.e., persons
      who have early component complement deficiencies, immunoglobulin deficiency,
      anatomic or functional asplenia, or HIV infection; recipients of hematopoietic
      stem cell transplant; and recipients of chemotherapy or radiation therapy for
      malignant neoplasms). This report summarizes current information on Hib
      epidemiology in the United States and describes Hib vaccines licensed for use in
      the United States. Guidelines for antimicrobial chemoprophylaxis of contacts of
      persons with Hib disease also are provided. 

PMID- 24572655
TI  - Synthetic biology and its regulation in the European Union.
AB  - The term synthetic biology is used increasingly, but without a clear definition.
      Most of the recent research carried out in this field is genetic engineering, as
      defined by current GMO-legislation in the EU. Synthetic biology has developed its
      own language. In vitro synthesis of DNA also carries the label synthetic biology.
      It is important to analyze whether present and future activities of synthetic
      biology are within the scope of existing EU-legislation. 

PMID- 24572657
TI  - From the editor.

PMID- 24572656
TI  - Robustness of Pseudomonas putida KT2440 as a host for ethanol biosynthesis.
AB  - Expansion of the burgeoning biofuels agenda involves not only the design of
      suitable genetic and metabolic devices but also their deployment into suitable
      hosts that can endure the stress brought about by the products themselves. The
      microorganisms that are easiest to genetically manipulate for these endeavors
      (e.g. Escherichia coli) are often afflicted by an undesirable sensitivity to the
      very product that they are engineered to synthesize. In this context, we have
      examined the resistance to the stress arising from ethanol synthesis and/or its
      addition to cultures of recombinant Pseudomonas putida, using as a benchmark the
      same trait in an E. coli strain. To this end, ethanologenic strains of these two
      species were constructed by functionally expressing pdc (pyruvate decarboxylase)
      and adhB (alcohol dehydrogenase) from Zymomonas mobilis. Recombinants were
      compared under anoxic conditions as ethanol producers, and cell survival, stress
      resistance, and phenotypic stability were quantified in each case. P. putida
      consistently outperformed E. coli in every ethanol tolerance test conducted -
      whether the alcohol was produced endogenously or added exogenously. These results
      highlight the value of this bacterium as a microbial cell factory for the
      production of biofuels owing to its naturally pre-evolved ability to withstand
      different kinds of chemical stresses. 

PMID- 24572658
TI  - The paradox of disability.

PMID- 24572659
TI  - Disability evaluation.

PMID- 24572660
TI  - Editor's note.

PMID- 24572661
TI  - American Academy of Disability Evaluating Physicians: history, mission and goals.

PMID- 24572662
TI  - Fitness for duty considerations in disabling occupational low-back pain.
AB  - Individuals who develop a work or non-work-related medical condition in the
      course of employment generally recover and return to full-duty status. There are,
      however, a small number who develop chronic diseases, delayed recovery syndromes
      or other similar disabling conditions. These difficult situations raise the
      question of whether the individual continues to be a qualified employee for the
      job he/she was hired to perform. Workers who develop stationary medical
      conditions with residual impairment, functional limitations, chronic pain
      syndromes or permanent medical restrictions represent significant medical, legal
      and ethical challenges for the treating or evaluating physician as well as the
      employer. Occupational low-back pain (OLBP) is not only one of the most commonly
      encountered of these type of conditions in the industrial setting, but also
      represents a significant disability challenge when material handling activities
      are considered essential functions of the job. This paper presents an appropriate
      medical, legal and ethical approach to identifying workers with OLBP risk and
      assisting the employer in either matching them to essential functions of jobs
      they may be qualified to hold or moving them into an appropriate disability
      pathway. 

PMID- 24572663
TI  - Management of debilitating injuries in a large industrial setting.
AB  - It has long been the goal of the occupational health specialist to avoid
      significant impairment or disability from debilitating injury at the work place.
      This paper is a description of effective and ineffective management strategies
      with disabling work injuries. Starting proactively with a preventive safety and
      health program, many of these injuries can be prevented or lessened
      significantly. When injury does occur, we must examine what can be done to ensure
      speedy recovery. The elements of prevention, including personal protective
      programs, ergonomics and pre-placement exams are reviewed. Injury care from early
      intervention with careful planning of case management involving all providers is
      also examined, as is the use of rehabilitation for early return to work including
      work conditioning and work hardening. Also included is how disability guides and
      a transitional work program can increase rapid recovery. Ultimately, although
      each element is essential as part of a good management program, the key to
      success lies in a good employee/employer relationship. 

PMID- 24572664
TI  - Evaluation of the cervicodorsal spine.
AB  - The proper evaluation of the cervical and dorsal spine is discussed, along with a
      presentation on various mechanisms for completing this evaluation in terms of
      making assessments on functional impairment. A discussion regarding testing and
      evaluation techniques is also provided. 

PMID- 24572665
TI  - Functional capacity evaluation and disability management.
AB  - The practical and theoretical basis behind the use of functional capacity testing
      is described. There is a description regarding the need for distinction between
      impairment and disability, necessitating the use of objective tests such as
      contained in a Functional Capacity Evaluation. A description regarding the
      mechanics of contemporary functional assessment is made, along with a statement
      of validity of the evaluation as well as practical considerations when
      considering why a Functional Capacity Evaluation should be performed. 

PMID- 24572666
TI  - Lower extremity impairment ratings. AMA Guides to the Evaluation of Permanent
      Impairment, Fourth Edition.

PMID- 24572667
TI  - Shiatsu massage therapy: a remarkable healing technique in spine pain.

PMID- 24572668
TI  - Investigation of the patient with HIV / AIDS and pain.

PMID- 24572670
TI  - 6th European congress on research in rehabilitation.

PMID- 24572671
TI  - Author indexVolume 7 (1996).

PMID- 24572673
TI  - Volume contentsVolume 7 (1996).

PMID- 24572675
TI  - Management and outcome of retinoblastoma with vitreous seeds.
AB  - PURPOSE: To report the treatment response of retinoblastoma with vitreous seeds
      to high-dose chemotherapy coupled with periocular carboplatin. DESIGN:
      Retrospective, interventional case series. PARTICIPANTS: Consecutive patients
      with retinoblastoma with vitreous seeds managed over 10 years at a comprehensive
      ocular oncology center and followed up for at least 12 months after the
      completion of treatment were included in this study. Institutional review board
      approval was obtained. INTERVENTION: High-dose chemotherapy with a combination of
      vincristine, etoposide, and carboplatin in patients with focal vitreous seeds and
      additional concurrent periocular carboplatin in patients with diffuse vitreous
      seeds. MAIN OUTCOME MEASURES: Tumor regression, vitreous seed regression, and eye
      salvage. RESULTS: After excluding the better eye of bilateral cases, 101 eyes of
      101 patients were part of the final analysis. All the patients belonged to Reese
      Ellsworth group VB, but on the International Classification of Retinoblastoma
      (ICRB), 21 were group C, 40 were group D, and 40 were group E. The mean basal
      diameter of the largest tumor was 11.8 +/- 4.7 mm. Mean tumor thickness was 7.5
      +/- 4.0 mm. Vitreous seeds were focal in 21 eyes and diffuse in 80 eyes.
      Chemotherapy cycles ranged from 6 to 12 (median, 6). Seventy-three eyes with
      diffuse vitreous seeds received a 15-mg posterior sub-Tenon carboplatin injection
      (range, 1-13 mg; median, 6 mg). Follow-up duration ranged from 13.4 to 129.2
      months (median, 48 months). External beam radiotherapy (EBRT) was necessary in 33
      eyes with residual tumor, vitreous seeds, or both. In all, 20 eyes (95%) with
      ICRB group C retinoblastoma, 34 eyes (85%) with group D retinoblastoma, and 23
      eyes (57.5%) with group E retinoblastoma were salvaged. Of 77 eyes that were
      salvaged, 74 (96%) had visual acuity of 20/200 or better. Twenty-four of 33
      chemotherapy failures (73%) regressed with EBRT. None of the patients
      demonstrated second malignant neoplasm or systemic metastasis. Factors predicting
      tumor regression and eye salvage were bilateral retinoblastoma and absence of
      subretinal fluid. Factors predicting vitreous seed regression were absence of
      subretinal fluid and subretinal seeds. CONCLUSIONS: Intensive management with
      primary high-dose chemotherapy and concurrent periocular carboplatin, and EBRT
      selectively in chemotherapy failures, provides gratifying outcome in
      retinoblastoma with vitreous seeds.

PMID- 24572676
TI  - Long-term, drug-free remission of sympathetic ophthalmia with high-dose, short
      term chlorambucil therapy.
AB  - OBJECTIVE: To evaluate the safety and effectiveness of short-term, high-dose
      chlorambucil therapy in achieving long-term, drug-free remission in the treatment
      of sympathetic ophthalmia (SO). DESIGN: Retrospective case series. PARTICIPANTS:
      Sixteen patients with SO treated with high-dose, short-term chlorambucil therapy
      between 1970 and 2010. METHODS: Descriptive and bivariate analyses were used to
      characterize disease and outcomes. MAIN OUTCOME MEASURES: Months of disease-free
      remission, prevalence rate of relapse, and prevalence of serious treatment
      related adverse events. RESULTS: Sixteen patients with SO treated with short
      term, high-dose chlorambucil were identified. Patients were treated with
      chlorambucil for a median of 14.0 weeks (mean, 14.5 weeks; range, 12.0-19.0
      weeks). Median follow-up was 98.5 months (mean, 139.1 months; range, 48-441
      months) from initiation of chlorambucil therapy. Control of inflammation was
      achieved in 100% of patients. Thirteen patients (81.3%) maintained vision of
      20/40 or better in the sympathizing eye. Four patients (25%) relapsed after a
      median of 83 months (mean, 131 months) after cessation of systemic therapy.
      Seventy-five percent of relapses were controlled with topical therapy only.
      Conjunctival Kaposi's sarcoma developed in 1 patient. No patient demonstrated
      systemic malignancy. CONCLUSIONS: Short-term, high-dose chlorambucil therapy
      provides sustained periods of drug-free remission. With median follow-up of more
      than 8 years (mean, 11.6 years; range, 4-37 years), there was a low rate of
      recurrence and minimal long-term serious health consequences or adverse events.
      Because SO may be a lifelong condition and because chlorambucil therapy may offer
      long-term, drug-free remission, this treatment may be worth considering early in
      the decision-making process for severe sight-threatening disease.

PMID- 24572677
TI  - Surgical debulking for idiopathic dacryoadenitis: a diagnosis and a cure.
AB  - PURPOSE: Idiopathic inflammatory tumor of the lacrimal gland, also called
      idiopathic dacryoadenitis, generally is treated with high-dose, long-term
      systemic corticosteroids, despite their limited success, high recurrence rate,
      and incidence of drug-induced side effects. This study describes the outcome of
      patients with idiopathic dacryoadenitis who were managed with surgical debulking.
      DESIGN: Retrospective case series from 2 tertiary referral centers. PARTICIPANTS:
      Forty-six patients (46 lacrimal glands). METHODS: Review of the clinical records,
      radiologic scans, and histopathologic specimens, with additional immunoglobulin
      G4 immunostaining. MAIN OUTCOME MEASURES: Clinical signs and symptoms at 2 months
      after the surgery and off medications. RESULTS: Before referral, 41% (19 of 46)
      of the patients had received systemic high-dose corticosteroids, after which they
      all showed recurrence, of whom 26% (5 of 19) became dependent on corticosteroids.
      At referral, all patients underwent debulking surgery of the inflammatory
      lacrimal gland mass for diagnostic and therapeutic reasons. Additionally,
      intralesional or systemic low-dose corticosteroids were given during the
      operation or the first postoperative days in 54% (25 of 46) of the patients. At 2
      months after the debulking surgery, a full clinical recovery was seen in 80% (37
      of 46) of the patients. A recurrence occurred in 8% (3 of 37) of the patients 4
      months and 2.2 and 4.6 years later. Surgical failure (20%; 9 of 46) was
      correlated with prior corticosteroid treatment (P = 0.002, Fisher exact test),
      but not with sclerosing inflammation present in 28% (13 of 46). The median follow
      up time was 7.2 years (range, 0.7-18 years). CONCLUSIONS: Debulking biopsy
      procedures for idiopathic dacryoadenitis, in addition to being diagnostic, may be
      therapeutic.

PMID- 24572678
TI  - Life is translation.
AB  - Evolutionary origin of translation represents one of the key questions that Carl
      Woese addressed in his work. Here we give a personal account of his results in
      this area and the effect they have had on the field. 

PMID- 24572679
TI  - Thermodynamics and high-pressure kinetics of a fast carbon dioxide fixation
      reaction by a (2,6-pyridinedicarboxamidato-hydroxo)nickel(II) complex.
AB  - The previously reported carbon dioxide fixation reaction by the planar terminal
      hydroxide complex [Ni(pyN2(Me2))(OH)](1-) in DMF has been further characterized
      by determination of the equilibrium constants K(eq)298 = 2.4 +/- 0.2 * 10(5) M(
      1) and K(eq)223 = 1.3 +/- 0.1 * 10(7) M(-1), as well as the volume of activation
      for the CO2 binding (DeltaV(on)(?223) = -21 +/- 3 cm(3) mol(-1)) and back
      decarboxylation (DeltaV(off)(?223) = -13 +/- 1 cm(3) mol(-1)) by high-pressure
      kinetics. The data are consistent with an earlier DFT computation, including the
      probable nature of the transition state, and support designating the reaction as
      one of the most completely investigated carbon dioxide fixation reactions of any
      type.

PMID- 24572674
TI  - Association of CAV1/CAV2 genomic variants with primary open-angle glaucoma
      overall and by gender and pattern of visual field loss.
AB  - PURPOSE: The CAV1/CAV2 (caveolin 1 and caveolin 2) genomic region previously was
      associated with primary open-angle glaucoma (POAG), although replication among
      independent studies has been variable. The aim of this study was to assess the
      association between CAV1/CAV2 single nucleotide polymorphisms (SNPs) and POAG in
      a large case-control dataset and to explore associations by gender and pattern of
      visual field (VF) loss further. DESIGN: Case-control study. PARTICIPANTS: We
      analyzed 2 large POAG data sets: the Glaucoma Genes and Environment (GLAUGEN)
      study (976 cases, 1140 controls) and the National Eye Institute Glaucoma Human
      Genetics Collaboration (NEIGHBOR) consortium (2132 cases, 2290 controls).
      METHODS: We studied the association between 70 SNPs located within the CAV1/CAV2
      genomic region in the GLAUGEN and NEIGHBOR studies, both genotyped on the
      Illumina Human 660WQuadv1C BeadChip array and imputed with the Markov Chain
      Haplotyping algorithm using the HapMap 3 reference panel. We used logistic
      regression models of POAG in the overall population and separated by gender, as
      well as by POAG subtypes defined by type of VF defect (peripheral or
      paracentral). Results from GLAUGEN and NEIGHBOR were meta-analyzed, and a
      Bonferroni-corrected significance level of 7.7 * 10(-4) was used to account for
      multiple comparisons. MAIN OUTCOME MEASURES: Overall POAG, overall POAG by
      gender, and POAG subtypes defined by pattern of early VF loss. RESULTS: We found
      significant associations between 10 CAV1/CAV2 SNPs and POAG (top SNP, rs4236601;
      pooled P = 2.61 * 10(-7)). Of these, 9 were significant only in women (top SNP,
      rs4236601; pooled P = 1.59 * 10(-5)). Five of the 10 CAV1/CAV2 SNPs were
      associated with POAG with early paracentral VF (top SNP, rs17588172; pooled P =
      1.07 * 10(-4)), and none of the 10 were associated with POAG with peripheral VF
      loss only or POAG among men. CONCLUSIONS: CAV1/CAV2 SNPs were associated
      significantly with POAG overall, particularly among women. Furthermore, we found
      an association between CAV1/CAV2 SNPs and POAG with paracentral VF defects. These
      data support a role for caveolin 1, caveolin 2, or both in POAG and suggest that
      the caveolins particularly may affect POAG pathogenesis in women and in patients
      with early paracentral VF defects.

PMID- 24572680
TI  - Photoresponsive supramolecular complexes as efficient DNA regulator.
AB  - Two supramolecular complexes of trans-1?CB[8] and trans-2?CB[8] were successfully
      achieved by the controlled selective complexation process of cucurbit[8]uril
      (CB[8]) with hetero-guest pair containing azobenzene and bispyridinium moieties
      in aqueous solution, exhibiting the reversibly light-driven movements of CB[8]
      upon the photocontrollable isomerization of azophenyl axle components.
      Significantly, the obtained bistable supramolecular complexes and their
      corresponding [2]pseudorotaxanes could act as a promising concentrator and
      cleavage agent to regulate the binding behaviors with DNA molecules. 

PMID- 24572681
TI  - Depression symptom clusters and their predictive value for treatment outcomes:
      results from an individual patient data meta-analysis of duloxetine trials.
AB  - We evaluated individual patient data from phase II to IV clinical trials of
      duloxetine in major depressive disorder (MDD) (34 studies, 13,887 patients). Our
      goal was to identify clusters of patients with similar depressive symptom
      patterns at baseline, as measured by the 17-item Hamilton Depression Rating Scale
      (HAMD-17), and to investigate their respective predictive value of outcomes as
      measured by the HAMD-17 total score. Five clusters were identified at baseline:
      1) "Lack of insight"; 2) "Sleep/sexual/somatic"; 3) "Typical MDD"; 4)
      "Gastrointestinal/weight loss"; and 5) "Mild MDD". However, it should be noted
      that cluster descriptors are not mutually exclusive. Analyses of the HAMD-17
      total score results over time were performed using the 18 randomized placebo
      and/or actively controlled studies representing 6723 patients. At the end of
      acute treatment (ranging from 4 to 36 weeks), different levels of effect sizes
      for active therapy (64.5% duloxetine) vs. placebo were detected by cluster. In 3
      out of 5 clusters (representing about 80% of the patients), the effect size was
      significantly different from 0, in favor of active therapy. The effect size was
      largest in those clusters with severe somatic symptoms ("Sleep/sexual/somatic"
      cluster [-0.4170], and "Gastrointestinal/weight loss" cluster [-0.338]). In
      conclusion, our cluster analysis identified 5 clinically relevant MDD patient
      clusters with specific mean treatment outcomes. Identification of MDD clusters
      may help to improve outcomes by adapting MDD treatment to particular clinical
      profiles. 

PMID- 24572684
TI  - Introduction.

PMID- 24572685
TI  - Clinical assessment of the shoulder.

PMID- 24572686
TI  - Shoulder pain and the instrumental musician.

PMID- 24572687
TI  - Management of work-related shoulder disorders.

PMID- 24572682
TI  - Trauma and posttraumatic stress disorder in Japan: results from the World Mental
      Health Japan Survey.
AB  - The purpose of the study was to report the prevalence of trauma exposure and
      PTSD, conditional risk of PTSD associated with each trauma exposure in the
      community population in Japan. An interview survey was conducted of a random
      sample of adult residents in 11 communities of Japan. Among 4134 respondents
      (response rate, 55%), data from those who completed the part 2 interview (n =
      1682) were analyzed with a weight for this subsample. Lifetime experiences of 27
      trauma events and PTSD were assessed using the WHO-Composite International
      Diagnostic Interview version 3.0. Sixty percent of the part 2 sample reported
      exposure to at least one lifetime traumatic event. Lifetime and 12-month PTSD
      prevalences were 1.3% and 0.7%, respectively. Percentage of all months lived with
      PTSD in the population was predominantly accounted for by physical/sexual
      assaults and having a child with serious illness, and unexpected death of loved
      one. Ten percent of respondents reported "private events", for which respondents
      did not have to describe the content, which accounted for 19% of months with
      PTSD. The lower prevalence of PTSD in Japan seems attributable to lower
      conditional risks of PTSD following these events, as well as different
      distributions of the events. The greater impact of events that occurred to loved
      ones rather than to oneself and "private events" on PTSD in Japan warrants
      further research of cross-cultural assessment of trauma exposure and cultural
      heterogeneity in the trauma-PTSD relationship. 

PMID- 24572688
TI  - Diagnosis and treatment of the reflex sympathetic dystrophy syndrome of the upper
      extremity.

PMID- 24572689
TI  - The shoulder in rheumatoid arthritis.

PMID- 24572690
TI  - Geriatric shoulder pain.

PMID- 24572691
TI  - Shoulder dysfunction secondary to axillary nerve palsy in the disabled.

PMID- 24572692
TI  - Research opportunities.
AB  - "Research Opportunities" is a regular feature of this journal that transmits
      information regarding sources of support for basic and applied research in spine
      and musculoskeletal rehabilitation. In the previous issue, this feature provided
      a historical and legislative overview of the National Center for Medical
      Rehabilitation Research (NCMRR), a newly created unit of the National Institutes
      of Health. In this issue, we provide additional information on the NCMRR,
      including the types of grants available through the center, possible research
      topics, and filing deadlines. 

PMID- 24572696
TI  - A waveguide frequency converter connecting rubidium-based quantum memories to the
      telecom C-band.
AB  - Coherently converting the frequency and temporal waveform of single and entangled
      photons will be crucial to interconnect the various elements of future quantum
      information networks. Of particular importance is the quantum frequency
      conversion of photons emitted by material systems able to store quantum
      information, so-called quantum memories. There have been significant efforts to
      implement quantum frequency conversion using nonlinear crystals, with non
      classical light from broadband photon-pair sources and solid-state emitters.
      However, solid state quantum frequency conversion has not yet been achieved with
      long-lived optical quantum memories. Here we demonstrate an ultra-low-noise solid
      state photonic quantum interface suitable for connecting quantum memories based
      on atomic ensembles to the telecommunication fibre network. The interface is
      based on an integrated-waveguide nonlinear device. We convert heralded single
      photons at 780 nm from a rubidium-based quantum memory to the telecommunication
      wavelength of 1,552 nm, showing significant non-classical correlations between
      the converted photon and the heralding signal. 

PMID- 24572697
TI  - Hendra virus vaccine, a one health approach to protecting horse, human, and
      environmental health.
AB  - In recent years, the emergence of several highly pathogenic zoonotic diseases in
      humans has led to a renewed emphasis on the interconnectedness of human, animal,
      and environmental health, otherwise known as One Health. For example, Hendra
      virus (HeV), a zoonotic paramyxovirus, was discovered in 1994, and since then,
      infections have occurred in 7 humans, each of whom had a strong epidemiologic
      link to similarly affected horses. As a consequence of these outbreaks,
      eradication of bat populations was discussed, despite their crucial environmental
      roles in pollination and reduction of the insect population. We describe the
      development and evaluation of a vaccine for horses with the potential for
      breaking the chain of HeV transmission from bats to horses to humans, thereby
      protecting horse, human, and environmental health. The HeV vaccine for horses is
      a key example of a One Health approach to the control of human disease. 

PMID- 24572700
TI  - Significant evidence of linkage for a gene predisposing to colorectal cancer and
      multiple primary cancers on 22q11.
AB  - OBJECTIVES: The genetic basis of colorectal cancer (CRC) is not completely
      specified. Part of the difficulty in mapping predisposition genes for CRC may be
      because of phenotypic heterogeneity. Using data from a population genealogy of
      Utah record linked to a statewide cancer registry, we identified a subset of CRC
      cases that exhibited familial clustering in excess of that expected for all CRC
      cases in general, which may represent a genetically homogeneous subset of CRC.
      METHODS: Using a new familial aggregation method referred to as the subset
      genealogic index of familiality (subsetGIF), combined with detailed information
      from a statewide tumor registry, we identified a subset of CRC cases that
      exhibited excess familial clustering above that expected for CRC: CRC cases who
      had at least one other primary tumor at a different site. A genome-wide linkage
      analysis was performed on a set of high-risk CRC pedigrees that included multiple
      CRC cases with additional primaries to identify evidence for predisposition loci.
      RESULTS: A total of 13 high-risk CRC pedigrees with multiple CRC cases with other
      primary cancers were identified. Linkage analysis identified one pedigree with a
      significant linkage signal at 22q11 (LOD (logarithm (base 10) of odds)=3.39).
      CONCLUSIONS: A predisposition gene or variant for CRC that also predisposes to
      other primary cancers likely resides on chromosome 22q11. The ability to use
      statewide population genealogy and tumor registry data was critical to identify
      an informative subset of CRC cases that is possibly more genetically homogeneous
      than CRC in general, and may have improved statistical power for predisposition
      locus identification in this study.

PMID- 24572701
TI  - Sphingosine kinase 1 promotes malignant progression in colon cancer and
      independently predicts survival of patients with colon cancer by competing risk
      approach in South asian population.
AB  - OBJECTIVES: Sphingosine kinase 1 (SphK1) phosphorylates the membrane
      sphingolipid, sphingosine, to sphingosine-1-phosphate (S1P), an oncogenic
      mediator, which drives tumor cell growth and survival. Although SphK1 has gained
      increasing prominence as an oncogenic determinant in several cancers, its
      potential as a therapeutic target in colon cancer remains uncertain. We
      investigated the clinical relevance of SphK1 expression in colon cancer as well
      as its inhibitory effects in vitro. METHODS: SphK1 expression in human colon
      tumor tissues was determined by immunohistochemistry and its clinicopathological
      significance was ascertained in 303 colon cancer cases. The effects of SphK1
      inhibition on colon cancer cell viability and the phosphoinositide 3-kinase
      (PI3K)/Akt cell survival pathway were investigated using a SphK1-selective
      inhibitor-compound 5c (5c). The cytotoxicity of a novel combination using SphK1
      inhibition with the chemotherapeutic drug, 5-fluorouracil (5-FU), was also
      determined. RESULTS: High SphK1 expression correlated with advanced tumor stages
      (AJCC classification). Using a competing risk analysis model to take into account
      disease recurrence, we found that SphK1 is a significant independent predictor
      for mortality in colon cancer patients. In vitro, the inhibition of SphK1 induced
      cell death in colon cancer cell lines and attenuated the serum-dependent PI3K/Akt
      signaling. Inhibition of SphK1 also enhanced the sensitivity of colon cancer
      cells to 5-FU. CONCLUSION: Our findings highlight the impact of SphK1 in colon
      cancer progression and patient survival, and provide evidence supportive of
      further development in combination strategies that incorporate SphK1 inhibition
      with current chemotherapeutic agents to improve colon cancer outcomes.

PMID- 24572702
TI  - Effects of watermelon supplementation on aortic hemodynamic responses to the cold
      pressor test in obese hypertensive adults.
AB  - BACKGROUND: Cold-induced increases in aortic blood pressure (BP) may cause
      adverse cardiac events in hypertensives by increasing ventricular afterload. L
      citrulline supplementation reduces BP at baseline and during the cold pressor
      test (CPT), but the effect on wave reflection (augmentation pressure (AP) and
      index (AIx)) is controversial. Our aim was to assess the effect of L-citrulline
      rich watermelon supplementation on aortic hemodynamic responses to CPT in
      hypertensive adults. METHODS: Brachial systolic BP (bSBP) and aortic systolic BP
      (aSBP), AP, AIx, AIx adjusted to 75 beats/min (AIx75), reflection time (Tr),
      first (P1) and second systolic peak (P2; wave reflection magnitude), heart rate
      (HR), and systolic time index (STI; myocardial oxygen demand) at baseline and
      during CPT and magnitude of the response from baseline to CPT were evaluated in
      13 individuals (10 women; 57+/-1 year; bSBP 151+/-5 mm Hg). Participants were
      randomized to a 6-week watermelon or placebo supplementation in a crossover
      design. RESULTS: Watermelon reduced (P < 0.05) bSBP, aSBP, P1, and P2 at baseline
      and CPT compared with placebo; thus, increases from baseline to CPT were
      unaffected. Watermelon did not affect AP, AIx, AIx75, and STI at baseline but
      decreased (P < 0.05) AP and STI during CPT and the increases in AP (~5mm Hg) and
      AIx75 (~7.3%) from baseline to CPT. CONCLUSIONS: Watermelon supplementation
      reduced aortic BP and myocardial oxygen demand during CPT and the magnitude of
      the cold-induced increase in wave reflection in obese adults with hypertension.
      Watermelon may provide cardioprotection by attenuating cold-induced aortic
      hemodynamic responses. CLINICAL TRIALS REGISTRATION: Clinicaltrial.gov register,
      NCT01185041.

PMID- 24572703
TI  - Developing hypertension guidelines: an evolving process.
AB  - Hypertension guidelines provide up-to-date information and recommendations for
      hypertension management to healthcare providers, and they facilitate translation
      of new knowledge into clinical practice. Guidelines represent consensus
      statements by expert panels, and the process of guideline development has
      inherent vulnerabilities. Between 1977 and 2003, under the direction of the
      National Institutes of Health (NIH), the Joint National Committee on Detection,
      Evaluation, and Treatment of High Blood Pressure (JNC) issued 7 reports. The
      evolution of the JNC recommendations reflects the acquisition of observational
      and clinical trial data and the availability of newer antihypertensive drugs.
      Despite 5 years in preparation, NIH did not release a JNC 8 report and recently
      made the decision to withdraw from issuing guidelines. The responsibility for
      issuing hypertension-related guidelines was transferred to the American Heart
      Association (AHA) and the American College of Cardiology. Without the endorsement
      of the NIH or the AHA, JNC 8 committee members recently published their guideline
      report. Notably, there have been discrepancies of JNC recommendations over time
      as well as discrepancies with recommendations of other professional
      organizations. The Institute of Medicine recently recommended criteria for
      "trustworthy" guidelines. Criticisms of the guideline process, and of the
      guidelines themselves, should not obscure their likely contribution to improved
      hypertension control and to decreases of mortality rates of stroke and
      cardiovascular disease over the past several decades. Nevertheless, translation
      of guidelines into clinical practice remains a challenge. 

PMID- 24572706
TI  - Call it what it is.

PMID- 24572705
TI  - Direct stimulation of angiotensin II type 2 receptor initiated after stroke
      ameliorates ischemic brain damage.
AB  - BACKGROUND: Stroke is a leading cause of death and disability; however, meta
      analysis of randomized controlled trials of blood pressure-lowering drugs in
      acute stroke has shown no definite evidence of a beneficial effect on functional
      outcome. Accumulating evidence suggests that angiotensin II type 1 receptor
      blockade with angiotensin II type 2 (AT2) receptor stimulation could contribute
      to protection against ischemic brain damage. We examined the possibility that
      direct AT2 receptor stimulation by compound 21 (C21) initiated even after stroke
      can prevent ischemic brain damage. METHODS: Stroke was induced by middle cerebral
      artery (MCA) occlusion, and the area of cerebral infarction was measured by
      magnetic resonant imaging. C21 (10 ug/kg/day) treatment was initiated immediately
      after MCA occlusion by intraperitoneal injection followed by treatment with C21
      once daily. RESULTS: We observed that ischemic area was enlarged in a time
      dependent fashion and decreased on day 5 after MCA occlusion. Treatment with C21
      initiated after MCA occlusion significantly reduced the ischemic area, with
      improvement of neurological deficit in a time-dependent manner without affecting
      blood pressure. The decrease of cerebral blood flow after MCA occlusion was also
      ameliorated by C21 treatment. Moreover, treatment with C21 significantly
      attenuated superoxide anion production and expression of proinflammatory
      cytokines, monocyte chemoattractant protein 1, and tumor necrosis factor alpha.
      Interestingly, C21 administration significantly decreased blood-brain barrier
      permeability and cerebral edema on the ischemic side. CONCLUSIONS: These results
      provide new evidence that direct AT2 receptor stimulation with C21 is a novel
      therapeutic approach to prevent ischemic brain damage after acute stroke.

PMID- 24572704
TI  - Risk stratification by ambulatory blood pressure monitoring across JNC classes of
      conventional blood pressure.
AB  - BACKGROUND: Guidelines propose classification of conventional blood pressure
      (CBP) into normotension (<120/<80 mm Hg), prehypertension (120-139/80-89 mm Hg),
      and hypertension (>=140/>=90 mm Hg). METHODS: To assess the potential
      differential contribution of ambulatory blood pressure (ABP) in predicting risk
      across CBP strata, we analyzed outcomes in 7,826 untreated people recruited from
      11 populations. RESULTS: During an 11.3-year period, 809 participants died (276
      cardiovascular deaths) and 639, 383, and 225 experienced a cardiovascular,
      cardiac, or cerebrovascular event. Compared with normotension (n = 2,639),
      prehypertension (n = 3,076) carried higher risk (P <= 0.015) of cardiovascular
      (+41%) and cerebrovascular (+92%) endpoints; compared with hypertension (n =
      2,111) prehypertension entailed lower risk (P <= 0.005) of total mortality (-14%)
      and cardiovascular mortality (-29%) and of cardiovascular (-34%), cardiac (-33%),
      or cerebrovascular (-47%) events. Multivariable-adjusted hazard ratios (HRs) for
      stroke associated with 24-hour and daytime diastolic ABP (+5 mm Hg) were higher
      (P <= 0.045) in normotension than in prehypertension and hypertension (1.98
      vs.1.19 vs.1.28 and 1.73 vs.1.09 vs. 1.24, respectively) with similar trends
      (0.03 <= P <= 0.11) for systolic ABP (+10 mm Hg). However, HRs for fatal
      endpoints and cardiac events associated with ABP did not differ significantly (P
      >= 0.13) across CBP categories. Of normotensive and prehypertensive participants,
      7.5% and 29.3% had masked hypertension (daytime ABP >=135/>=85 mm Hg). Compared
      with true normotension (P <= 0.01), HRs for stroke were 3.02 in normotension and
      2.97 in prehypertension associated with masked hypertension with no difference
      between the latter two conditions (P = 0.93). CONCLUSION: ABP refines risk
      stratification in normotension and prehypertension mainly by enabling the
      diagnosis of masked hypertension.

PMID- 24572708
TI  - From the editor.

PMID- 24572707
TI  - Application of a three-dimensional (3D) particle tracking method to microfluidic
      particle focusing.
AB  - In this paper, a defocusing-based three-dimensional (3D) particle tracking method
      is presented and demonstrated for microfluidic particle focusing applications.
      Previous work in particle focusing has verified particle position in two
      dimensions (2D) using micro-streak velocimetry, or confocal and stereoscopic
      setups for 3D tracking. The results obtained from the methodology presented are
      compared with the theoretical and previously observed trends, and it is shown
      that the defocusing technique provides a simple and precise tool for determining
      the 3D locations of cell-sized particles in microscale flows (Re <= 100).
      Although similar methods exist for micro-particle image velocimetry (MU-PIV)
      applications, this is the first implementation of this technique for particle
      focusing applications. 

PMID- 24572709
TI  - Is there such a thing as myofascial pain?

PMID- 24572710
TI  - Editor's note.

PMID- 24572711
TI  - American Academy of Disability Evaluating Physicians: history, mission and goals.

PMID- 24572712
TI  - Impairment ratings and disability issues of the upper extremity.
AB  - Determination of a fair and consistent permanent impairment rating is a very
      important part of the injured worker's care. This rating is a medical
      determination and is based on objective and consistent physical findings.
      Conversion of these findings into a percent of impairment is greatly facilitated
      by the use of guidelines which enable different examiners to be consistent in
      their determinations. The most widely used guide is the Guides to the Evaluation
      of Permanent Impairment, published by the American Medical Association.
      Disability is a legal determination which attempts to quantitate how the
      impairment will affect the injured person. Disability takes into account the
      worker's age, education, experience, and other social and economic factors. In
      the United States, disability is usually determined by the courts, while in other
      parts of the English-speaking world, the physician who does the impairment rating
      may be expected to estimate the disability as well as the impairment. This
      article will discuss some aspects of determination of impairment of the upper
      extremity, using the AMA Guides as the primary guideline. 

PMID- 24572713
TI  - Coordinating rehabilitation efforts and the disability evaluating process.
AB  - Treating industrial injuries/dysfunctions present greater challenges for the
      treating physician and rehabilitation team. The treatment and documentation needs
      of injured workers require a coordinated effort of the entire rehabilitation team
      in order to bring the disability evaluating process to an efficient and final
      conclusion. This manuscript presents the authors' personal clinical approaches to
      industrial injuries, focusing on the rehabilitation process: what to do, when to
      do it, and when to stop and proceed along a different plan. This paper will also
      address issues of completing the disability evaluating process while meeting the
      needs of the patient, employer, case manager, and payor source. The importance of
      the multi-disciplinary rehabilitation team and communication with the employer
      through the case manager, patient and family will be described. The use of
      Functional Capacity Evaluation, Job Analysis and other return to work and
      disability assessment modalities will be discussed as related to coordination
      with other rehabilitation efforts. 

PMID- 24572714
TI  - Evaluation of the peripheral nervous system in disability management: practical
      aspects in lower back pain.
AB  - Lower back pain (LBP) is a common condition with profound economic and social
      consequences. A conservative, symptomatic, goal-oriented management program is
      advocated by most, emphasizing pain relief and restoration of functional
      capacity. Still, LBP is recurrent in approximately 50% of patients and up to 5
      10% experience chronic intractable pain. This article describes how to evaluate
      and rehabilitate the patient with spinal impairment (SI). All is summarized in a
      diagnostic/treatment algorithm as used in the spine rehabilitation center. Causes
      of LBP, components of the patient history and physical, diagnostic test usage and
      management options are summarized in tables for future reference. Lastly,
      preventative measures are discussed which, when implemented within a treatment
      program, may prevent future reoccurrences. 

PMID- 24572715
TI  - The evolution and mechanics of the midfoot and hindfoot.
AB  - The foot and ankle have been an important part in the development of human gait
      and the erect posture of man. This paper presents several important evolutionary
      and biomechanical insights to the function of the midfoot and rearfoot. The bony
      architecture of the foot and ankle has enhanced the ability of man to walk in an
      upright posture. The complex movements of supination and pronation was
      established as a result of positional changes of the talus and calcaneus. The
      human foot has adapted to a bipedal striding gait by forming a compact structure
      that can absorb high ground reaction forces and provide a lever for push-off.
      Certain mechanical disorders of the foot and ankle may result from alterations of
      several evolutionary features. Excessive pronation and supination are the two
      major categories of mechanical disorders of the foot and ankle. The restoration
      of normal foot mechanics offers an important treatment approach to mechanical
      dysfunction of the foot and ankle. 

PMID- 24572716
TI  - Research on complementary therapies in physical medicine and rehabilitation.

PMID- 24572717
TI  - Pharmacotherapy of Pain in HIV/AIDS.

PMID- 24572719
TI  - New hybrid Cd(II) compounds: synthesis and structural characterization.
AB  - In an acidic solution, the room-temperature reactions of CdX2 (X(-) = Cl(-), Br(
      ) or CH3COO(-)) and organic N-heterocyclic molecules with or without SCN(-)/SeCN(
      )/dca(-) (dca(-) = dicyanamide) created the five new hybrid Cd(ii) compounds
      [H2(4,4'-dtdpy)]2[CdBr4]SO4.2.5H2O (dtdpy = dithiodipyridine) 1, [H(2,2'
      dtdpy)]2[CdBr4] 2, [(Hbim)2CdCl2(SCN)2] (bim = 2,2'-biimidazole) 3,
      [H2(pip)][Cd(SCN)4] (pip = piperazine) 4 and [CdL2] (L = HNC(OH)N(-)CN) 5. X-ray
      single-crystal diffraction analysis revealed that: (i) compound 1 is a double
      salt of [H2(4,4'-dtdpy)]SO4 and [H2(4,4'-dtdpy)][CdBr4], [H2(4,4'-dtdpy)]SO4
      shows a two-dimensional (2D) supramolecular layer structure and [H2(4,4'
      dtdpy)][CdBr4] is distributed in the space between the supramolecular layers;
      (ii) compounds 2 and 3 are mononuclear molecular entities. Of those, 2,2'-dtdpy
      and bim were only in situ monoprotonated; (iii) compound 4 contains a 2D
      supramolecular layered structure which is based on [Cd(SCN)4](2-) chains
      H2(pip)(2+)via NSCNNpip interactions; (iv) the three-dimensional (3D) compound 5
      exhibits a rutile-related (4.6(2))2(4(2).6(10).8(3))-topology. The ligand L
      originates from the in situ nucleophilic addition of H2O with one -CN group of
      dca(-). Upon excitation, the solid-state compounds 3 and 4 emit blue light, and
      the solid-state compound 5 emits violet light. 

PMID- 24572720
TI  - Organelle evolution, fragmented rRNAs, and Carl.
AB  - I am honored to have been asked to contribute to this memorial issue, although I
      cannot claim to have known Carl Woese well. Carl's insights and the discoveries
      that his research group made over the years certainly stimulated my own research
      program, and at several points early on, interactions with him were pivotal in my
      career. Here I comment on these personal dealings with Carl and emphasize his
      influence in two areas of long-standing interest in my lab: organelle evolution
      and rRNA evolution. 

PMID- 24572721
TI  - Husbandry risk factors associated with hock pododermatitis in UK pet rabbits
      (Oryctolagus cuniculus).
AB  - Pododermatitis, often called 'sore hocks', is a chronic, granulomatous,
      ulcerative dermatitis which most commonly affects the plantar aspect of the
      caudal metatarsal and tarsal areas. Pododermatitis is a common clinical finding
      in the pet rabbit population, but no data is available regarding the actual
      prevalence of this condition in the UK pet rabbit population or possible
      husbandry-related factors which may predispose pet rabbits to development of this
      condition. It was the aim of this study to determine the prevalence of
      pododermatitis within a sample pet rabbit population, and study possible
      correlations with husbandry, sex, breed and origin of the rabbits. Findings
      suggested that young rabbits are at a lower risk of pododermatitis compared with
      older rabbits; female domestic rabbits are more predisposed to pododermatitis
      than males; and 100 per cent of the neutered females examined showed clinical
      evidence of pododermatitis. The effect that different types of bedding may have
      on the prevalence of pododermatitis was also investigated. This study also
      produced a scoring system which can be used to score clinical cases. Our study is
      of clinical importance because it helps to recognise many of the factors which
      predispose pet rabbits to pododermatitis, representing the first step towards
      increased awareness of this extremely common problem. 

PMID- 24572722
TI  - Pathogen presence in feral pigs and their movement around two commercial
      piggeries in Queensland, Australia.
AB  - Feral pigs are wild animal reservoirs of infectious pathogens transmissible to
      other species, all of which are transmissible to domestic pigs. The objective of
      this study was to detect the presence of harmful production-limiting pathogens;
      Brucella suis, Leptospira species, Lawsonia intracellularis, Mycoplasma
      hyopneumoniae and Actinobacillus pleuropneumoniae in a feral pig population
      within a 10 km radius of two large-scale commercial piggeries in Southern
      Queensland, Australia. The movement pattern of six pigs within the feral
      population was also investigated using geographic positioning system collars. All
      pathogens were present in the feral pig population except for A pleuropneumoniae.
      The true seroprevalence (TP) from 83 serum samples was 10.5 per cent for B suis,
      48.6 per cent for Leptospira species, 100 per cent for L intracellularis and 42.1
      per cent for M hyopneumoniae. Of 72 lung samples, 27.6 per cent were positive for
      M hyopneumoniae. Serum samples from 86 domestic sows within the study region were
      positive for Leptospira species (TP 2.1 per cent), L intracellularis (TP 100 per
      cent) and M hyopneumoniae (TP 100 per cent). The majority of feral pig movement
      was within 5 km of the piggeries, with one approaching to 100 m of the free-range
      piggery. The presence of pathogens in feral pigs in such close proximity to
      commercial piggeries could pose a biosecurity risk. 

PMID- 24572723
TI  - Novel vital signs-controlled, patient-assisted intravenous analgesia using
      remifentanil for labour and delivery.

PMID- 24572724
TI  - Sciatic nerve ischaemia after iliac artery occlusion balloon catheter placement
      for placenta percreta.
AB  - Placenta percreta is a complex obstetric condition and a cause of life
      threatening peripartum haemorrhage. National guidelines advise preoperative
      placement of internal iliac artery occlusion balloon catheters in such cases to
      reduce haemorrhage, avoid caesarean hysterectomy and preserve fertility. Maternal
      complications of prophylactic occlusion balloon catheter insertion include
      puncture-site complications and arterial thrombosis, the signs of which are
      usually immediately clinically evident. Presentation of ischaemic nerve injury
      attributable to iliac artery thrombosis secondary to the presence of an occlusion
      balloon catheter is as yet unreported. Awareness of this possible complication
      and local unit guidelines may allow early detection and treatment. 

PMID- 24572727
TI  - Anatomy and kinesiology of the ankle and foot.

PMID- 24572725
TI  - Cheap, gram-scale fabrication of BN nanosheets via substitution reaction of
      graphite powders and their use for mechanical reinforcement of polymers.
AB  - As one of the most important two-dimensional (2D) materials, BN nanosheets
      attracted intensive interest in the past decade. Although there are many methods
      suitable for the preparation of BN sheets, finding a cheap and nontoxic way for
      their mass and high-quality production is still a challenge. Here we provide a
      highly effective and cheap way to synthesize gram-scale-level well-structured BN
      nanosheets from many common graphite products as source materials. Single
      crystalline multi-layered BN sheets have a mean lateral size of several hundred
      nanometers and a thickness ranging from 5 nm to 40 nm. Cathodoluminescence (CL)
      analysis shows that the structures exhibit a near band-edge emission and a broad
      emission band from 300 nm to 500 nm. Utilization of nanosheets for the
      reinforcement of polymers revealed that the Young's modulus of BN/PMMA composite
      had increased to 1.56 GPa when the BN's fraction was only 2 wt.%, thus
      demonstrating a 20% gain compared to a blank PMMA film. It suggests that the BN
      nanosheet is an ideal mechanical reinforcing material for polymers. In addition,
      this easy and nontoxic substitution method may provide a universal route towards
      high yields of other 2D materials. 

PMID- 24572726
TI  - Swallowing impairment and pulmonary dysfunction in Parkinson's disease: the
      silent threats.
AB  - INTRODUCTION: Swallowing disorders and respiratory impairment are frequent in
      Parkinson's disease (PD) patients, and aspiration pneumonia remains the leading
      cause of death among these subjects. OBJECTIVE: The objective of this study was
      to investigate whether there is an association between pulmonary impairment and
      swallowing dysfunction in PD patients. METHODS: A cross-sectional study with a
      comparison group was conducted with PD patients. Subjects were submitted to
      demographic questionnaires and underwent spirometric and videofluorographic
      assessments. Significance level was considered at 95% (p<0.05). RESULTS: Among 35
      PD patients, 40% presented with swallowing complaints. However, 22% of the
      clinically asymptomatic patients presented airway food penetration when submitted
      to videofluoroscopy. In 20% of PD patients material entered the airways and there
      was contact with the vocal folds in 7%. However, there was an efficient cleaning
      with residue deglutition in almost all patients. No penetration/aspiration was
      detected among the controls. Respiratory parameters were below the normal
      predicted values in PD patients when compared to the healthy controls.
      CONCLUSION: These data suggest an association between pulmonary dysfunction and
      swallowing impairment in PD patients; even in patients without swallowing
      complaints, impaired pulmonary function can be detected.

PMID- 24572729
TI  - Entrapment neuropathies of the foot and ankle.

PMID- 24572728
TI  - Acute and chronic compartment syndromes of the lower leg.

PMID- 24572731
TI  - Ankle RehabilitationA Sample Program for Injuries Involving the Ankle Joint.

PMID- 24572730
TI  - Persistent ankle pain after ankle sprain: diagnosis and treatment considerations.

PMID- 24572732
TI  - Ankle taping and orthoses: a review of the literature.

PMID- 24572733
TI  - Research opportunities.
AB  - "Research opportunities" is a regular feature of the Journal that attempts to
      provide relevant and timely information regarding funding opportunities for basic
      and applied research in back and musculoskeletal rehabilitation. This issue
      contains the third and final column in a series devoted to the National Center
      for Medical Rehabilitation Research (NCMRR), a major new center with the National
      Institutes of Health (NIH) devoted to the conduct and support of research in
      medical rehabilitation. Previous columns provided a historical and legislative
      overview of the NCMRR, and described the types of grants available through the
      center. This issue describes the types and range of research activity reported by
      the center. 

PMID- 24572735
TI  - From the editor.

PMID- 24572736
TI  - Introduction.

PMID- 24572737
TI  - Comprehensive study of the spin-charge interplay in antiferromagnetic La(2
      x)Sr(x)CuO4.
AB  - The origin of the pseudogap and its relationship with superconductivity in the
      cuprates remains vague. In particular, the interplay between the pseudogap and
      magnetism is mysterious. Here we investigate the newly discovered nodal gap in
      hole-doped cuprates using a combination of three experimental techniques applied
      to one, custom made, single crystal. The crystal is an antiferromagnetic La(2
      x)Sr(x)CuO4. with x=1.92%. We perform angle-resolved photoemission spectroscopy
      measurements as a function of temperature and find: quasi-particle peaks, Fermi
      surface, anti-nodal gap and below 45 K a nodal gap. Muon spin rotation
      measurements ensure that the sample is indeed antiferromagnetic and that the
      doping is close, but below, the spin-glass phase boundary. We also perform
      elastic neutron scattering measurements and determine the thermal evolution of
      the commensurate and incommensurate magnetic order, where we find that a nodal
      gap opens well below the commensurate ordering at 140 K, and close to the
      incommensurate spin density wave ordering temperature of 30 K.

PMID- 24572738
TI  - Woese on the received view of evolution.
AB  - As part of his attempt to reconstruct the earliest phase of the evolution of life
      on Earth, Woese produced a compelling critique of the received view of evolution
      from the 20th century. This paper explicitly articulates two related features of
      that critique that are fundamental but the first of which has not been
      sufficiently clearly recognized in the context of evolutionary theorizing: (1)
      according to Woese's scenario of communal evolution during life's earliest phase
      (roughly, the first billion years of life on Earth), well-defined biological
      individuals (and, thus, individual lineages) did not exist; and (2) during that
      phase, evolutionary change took place through ubiquitous horizontal gene transfer
      (HGT) rather than through vertical transmission of features (including genes) and
      the combinatorics of HGT was the dominant mechanism of evolutionary change. Both
      factors present serious challenges to the received view of evolution and that
      framework would have to be radically altered to incorporate these factors. The
      extent to which this will be necessary will depend on whether Woese's scenario of
      collective early evolution is correct. 

PMID- 24572740
TI  - Casting a long shadow in the classroom: an educator's perspective of the
      contributions of Carl Woese.
AB  - "What does one do when the giants pass away?" remarked a very famous
      microbiologist to me, soon after the death of Carl Woese in late 2012. I teach
      microbiology and introductory cell and molecular biology at a small undergraduate
      institution; Woese's example and contributions have long been part of every class
      I teach, and with good reason. Thus, I didn't know quite what to say to my
      colleague at first; I was still mentally processing the event. 

PMID- 24572739
TI  - Possible role of songbirds and parakeets in transmission of influenza A(H7N9)
      virus to humans.
AB  - Avian-origin influenza A(H7N9) recently emerged in China, causing severe human
      disease. Several subtype H7N9 isolates contain influenza genes previously
      identified in viruses from finch-like birds. Because wild and domestic songbirds
      interact with humans and poultry, we investigated the susceptibility and
      transmissibility of subtype H7N9 in these species. Finches, sparrows, and
      parakeets supported replication of a human subtype H7N9 isolate, shed high titers
      through the oropharyngeal route, and showed few disease signs. Virus was shed
      into water troughs, and several contact animals seroconverted, although they shed
      little virus. Our study demonstrates that a human isolate can replicate in and be
      shed by such songbirds and parakeets into their environment. This finding has
      implications for these birds' potential as intermediate hosts with the ability to
      facilitate transmission and dissemination of A(H7N9) virus. 

PMID- 24572743
TI  - The 64th regional meeting (kita area).

PMID- 24572741
TI  - Evidence of impairment of normal inflammatory reaction by a high-fat diet.
AB  - The murine dorsal air pouch model is a valuable tool for studying acute
      peripheral inflammatory reactions. We used this model to study the effect of diet
      on the onset of acute inflammation. Mice were fed a normal or a high-fat diet
      (HFD) for 5 weeks. Air pouches were raised and injected with non-stimulating
      (saline) or stimulating solution (saline containing lipopolysaccharides). After 4
      h, leukocytes in the pouch fluid were enumerated, sorted and their viability
      measured. Cytokine/chemokine levels in the cell-free fluid were measured using a
      cytometric bead assay. Gene expression level was measured in leukocytes and in
      lining tissues using comparative real-time PCR. Leukocyte migration and
      cytokine/chemokine secretion were decreased substantially in mice fed the HFD. In
      contrast, leptin levels were elevated. Gene expression profiles in leukocytes
      recovered from the pouch and in the pouch-lining tissue (believed to have an
      important role in the initiation of granulocyte recruitment) were depressed.
      Genes encoding CC and CXC family chemokines were among the most negatively
      affected. These results suggest that a HFD can alter peripheral tissue activation
      as well as leukocyte recruitment and response, thereby affecting the development
      of an effective local immune response, which could have deleterious consequences.

PMID- 24572744
TI  - The 66th regional meeting (seinan area).

PMID- 24572745
TI  - The 129th regional meeting (kanto area).

PMID- 24572742
TI  - Family studies of type 1 diabetes reveal additive and epistatic effects between
      MGAT1 and three other polymorphisms.
AB  - In a recent study on multiple sclerosis (MS), we observed additive effects and
      epistatic interactions between variants of four genes that converge to induce T
      cell hyperactivity by altering Asn-(N)-linked protein glycosylation: namely, the
      Golgi enzyme MGAT1, cytotoxic T-lymphocyte antigen 4 (CTLA-4), interleukin-2
      receptor-alpha (IL2RA) and interleukin-7 receptor-alpha (IL7RA). As the CTLA-4,
      IL2RA and IL7RA variants are associated with type 1 diabetes (T1D), we examined
      for joint effects in T1D. Employing a novel conditional logistic regression for
      family-based data sets, epistatic and additive effects were observed using 1423
      multiplex families from the Type 1 Diabetes Genetic Consortium data set. The
      IL2RA and IL7RA variants had univariate association in MS and T1D, whereas the
      MGAT1 and CTLA-4 variants associated with only MS or T1D, respectively. However,
      similar to MS, the MGAT1 variant haplotype interacted with CTLA4 (P=0.03), and a
      combination of IL2RA and IL7RA (P=0.01). The joint effects of MGAT1, CTLA4,
      IL2RA, IL7RA and the two interactions using a multiple conditional logistic
      regression were statistically highly significant (P<5 * 10(-10)). The MGAT1-CTLA
      4 interaction was replicated (P=0.01) in 179 trio families from the Genetics of
      Kidneys in Diabetes study. These data are consistent with defective N
      glycosylation of T cells contributing to T1D pathogenesis. 

PMID- 24572747
TI  - From the editor.

PMID- 24572746
TI  - The 124th regional meeting (kinki area).

PMID- 24572748
TI  - Technological advance amidst humanistic decline: Ignoring muscle evaluation and
      treatment in the modern age of medicine.

PMID- 24572749
TI  - Call for letters to the editor.

PMID- 24572750
TI  - Comprehensiveness, uniformity and standardization in the evaluation of patients
      with complaints of pain.
AB  - An increasing number of physicians from a variety of disciplines are specializing
      in the treatment of patients with pain, and reporting treatment success using
      disparate interventions. Due to the lack of standardized evaluations of patients
      with pain, however, it has been impossible to reasonably assess the claims of any
      facility and even more difficult to compare the types of treatments from a
      variety of treatment settings. This paper will describe the process of the
      fomation of the Uniform Outcome Measures Committee of the American Academy of
      Pain Medicine. The deliberations of the Committee and the status of the
      development of a data collection system package will be described. 

PMID- 24572751
TI  - The reintroduction of an exercise program to directly treat low back pain of
      muscular origin.
AB  - Decades of debate have yet to yield a universal solution to the treatment of low
      back pain, a problem that afflicts 80% of adults in the United States at some
      point of their lives [1,2]. Exercise, in general, has become widely recognized as
      playing a large role in the rehabilitation of back pain sufferers. Yet, there is
      no consensus on which types of exercises to utilize. Most exercise techniques
      address the muscles with the specific purpose of impacting the skeleton or the
      spinal cord and nerve roots, rather than the muscles themselves. This reinforces
      the notion that muscles are not the direct source of pain, but rather only
      reflect pathology elsewhere. We reintroduce a rational exercise regimen first
      developed by Hans Kraus, M.D. in 1949. This regimen was shaped over a period of
      several years, through usage by thousands of back pain sufferers. It directly
      addresses specific trunk muscle deficiencies and tension, which are postulated by
      the authors to be the major factors producing low back pain. The exercise
      protocol has shown to be highly effective and inexpensive to administer on a wide
      scale basis. Recent clinical experiences utilizing the Kraus techniques are
      discussed. 

PMID- 24572752
TI  - The New York Pain Treatment Program protocol: a structured physical therapy
      approach for treating the muscular components of chronic pain syndromes.
AB  - Although Myofascial Pain Syndrome (MPS) is the most common diagnosis for injured
      workers [1], there is no uniform description or definition of MPS in the medical
      literature. Often the phrase myofascial pain is used to describe a variety of
      difficult to classify pain syndromes, resulting in confused and contradictory
      treatment approaches. Correct diagnosis and successful treatment of patients
      suffering from MPS must be based on a firm understanding of the muscular
      component of chronic pain syndromes. The New York Pain Treatment Program protocol
      in use at Lenox Hill Hospital is based on classification, diagnosis and treatment
      guidelines, developed by Dr. Hans Kraus, that recognize four types of muscle pain
      (tension, spasm, deficiency, and trigger points). It is the author's hope that
      this presentation will assist other clinicians in developing optimal
      rehabilitation programs. 

PMID- 24572753
TI  - A review of utilization of diagnostic imaging in the evaluation of patients with
      back pain: The when and what of back pain imaging.
AB  - PURPOSE: To review the indications for imaging in patients with back pain.
      METHODS: The author's experience as a clinical neuroradiologist in dealing with
      both referring physicians and their patients with back pain form the basis of
      this manuscript. Several texts and recent peer reviewed papers dealing with
      imaging of the spine were consulted. RESULTS: There are controversies over when
      to image and the appropriate imaging modality to be used. The author presents his
      views on the sources of these controversies and his philosophy on imaging
      patients with back pain. A brief review of the major imaging findings in
      degenerative and non-degenerative causes of back pain is presented. To fully
      appreciate and see examples of these imaging findings, the reader should read
      texts devoted to spinal imaging. CONCLUSION: Controversy over the decision of
      when to perform imaging of patients with back pain persist. From the perspective
      of the radiologist there is little controversy over the choice of imaging studies
      to be performed. MRI is superior to all other tests in the identification of
      degenerative and non-degenerative causes of back pain. CT without intrathecal
      contrast is an excellent test for degenerative disease but will often fail to
      detect non-degenerative (e.g. neoplastic) causes of back pain.

PMID- 24572754
TI  - Epidural steroid injections for the treatment of lumbosacral radiculopathy.
AB  - OBJECTIVE: While there is an extensive body of literature concerning the use of
      epidural steroid injections in the treatment of sciatica, most of the literature
      is descriptive or anecdotal. There are few controlled studies regarding efficacy
      of this treatment modality. While there are few published reports of serious
      complications of this therapy, warnings about the hazards of epidural steroid
      injections occasionally appear in both medical and lay literature. It is the
      purpose of this review to assess the existing evidence for efficacy of epidural
      steroid injections for sciatica and to assess the risks of this procedure. DATA
      SOURCES: Peer reviewed medical literature from 1930 to the present was reviewed
      in order to survey reports regarding pathophysiology of radiculopathy, mechanism
      of action of epidural corticosteroids, controlled efficacy studies, reports on
      series of epidural steroid injections for sciatica, reports of adverse effects of
      epidural and intrathecal steroid injections, review articles of epidural and
      intrathecal steroid injections, and studies of the behavioral and histological
      effects of epidural steroids and their vehicle in animals. STUDY SELECTION:
      Studies and review articles were selected from Medline search and from the
      author's files of older literature. DATA SYNTHESIS: RESULTS of this review are
      qualitative. It was felt that there was insufficient controlled data to analyze
      efficacy or safety studies in a quantitative fashion. RESULTS: Radiculopathy
      following disc herniation appears to produce either mechanical or chemical nerve
      root inflammation. Epidurally injected corticosteroids most likely exert a
      beneficial effect through anti-inflammatory rather than direct analgesic
      mechanisms. Most descriptive studies report beneficial effects of epidural
      steroids in the majority of cases of radiculopathy, but not for other causes of
      low back pain. Most of the few controlled studies report epidural steroids to be
      more efficacious than placebo or epidural local anesthetic alone. Most patients
      who respond favorably continue to show improvement for many months. Several
      neurologic complications have been reported after intrathecal steroid injections,
      most following multiple intrathecal injections. Four cases of epidural abscess,
      one case of bacterial meningitis, and one case of aseptic meningitis have been
      reported following epidural steroid injections. CONCLUSIONS: The majority of the
      published literature supports the notion that epidural steroids provide relief of
      pain from lumbosacral radiculopathy. There is anecdotal evidence that multiple
      intrathecal steroid injections may be associated with neurological dysfunction,
      but there is very little evidence that epidural steroids are neurotoxic.

PMID- 24572755
TI  - Algometry in the daily practice of pain management.
AB  - PURPOSE: This is a review article to update the clinical applications of pressure
      pain sensitivity (PPS) measurement by pressure algometry (PA) [1,2]. BASIC
      PROCEDURES: The basic literature on pressure algometry has been reviewed with
      emphasis on new developments. The author's and his co-workers' experience with
      PA, extending several years, are also included along with some unpublished
      research results. FINDINGS: The high reliability and validity of PA for
      quantification of PPS has been proven by several authors. The specificity and
      sensitivity of PA in detection of trigger points (TrPs) is also very good. PA is
      also useful in evaluation of treatment results. PA can document the decreased PPS
      after 'preinjection (regional) blocks' administered prior to trigger point
      injections (TPIs). A study of ten patients with failed back surgery included 20
      muscles. PA documented long-term improvement (150 days) which corresponded to a
      decrease in pain rating. Treatment consisted of needling and infiltration of the
      entire trigger point (TrP) extending to taut band. Another study showed that
      physicians were unable to produce 4 kg of pressure, which is critical for
      diagnosis of fibromyalgia. CONCLUSIONS: Quantification of fibromyalgia diagnosis
      by PA is necessary for abnormal tenderness (pain on 4 kg pressure). The critical
      pressure for TrP, tender spots is a pressure pain threshold lower by 2 kg/cm2
      relative to a normally sensitive corresponding control point.

PMID- 24572756
TI  - Therapeutic trials with thyroid hormones in chemically euthyroid patients with
      myofascial pain and complaints suggesting mild thyroid insufficiency.
AB  - OBJECTIVE: To determine why patients with normal function of the pituitary
      thyroid axis, myofascial pain, and other symptoms resembling those of
      hypothyroidism respond to a slightly supraphysiological dose of levothyroxin
      administration. DESIGN: Review and analysis of author's records drawn from a data
      base of therapeutic trials. INTERVENTION: Oral administration of levothyroxin,
      0.2 mg daily for at least 3 months. MAIN OUTCOME MEASURES: Patient interviews and
      physical examinations by author. Measurement of differences in paired BMR, serum
      cholesterol, and subjective response after 3 or more months of thyroid hormone
      administration, using each patient as his or her own control. SUMMARY: Fifty
      seven chemically euthyroid adults of both sexes with myofascial pain and
      hypothyroid-like symptoms were treated with a slightly supraphysiological dose,
      0.2 mg, of levothyroxin daily. Cases were selected recently from a database of
      367 therapeutic trials performed by the author between 1954 and 1983. All
      patients had a normal thyroid profile, and a serum TSH measurement before
      initiating levothyroxin replacement. BMRs and serum cholesterol determinations
      before and after at least 3 months of thyroid hormone therapy were compared. A
      graph was constructed in which each point displayed three responses for each
      patient: change in resting oxygen consumption, following a 12-h fast (BMR);
      change in serum cholesterol; and symptom response score. Thirteen TSH levels were
      slightly elevated. Analysis of the graph suggests that almost all patients with:
      (1) normal function of the pituitary thyroid axis; (2) non-inflammatory
      myofascial pain refractory to physical medicine and trigger point therapy; and
      (3) symptoms and signs resembling hypothyroidism, responded to thyroid hormone
      therapy. The responses suggest correction of a peripheral block to thyroid
      hormone in patients with normal pituitary thyrotroph function.

PMID- 24572757
TI  - Theory and practice of myofascial pain as both practicing clinician and patient.

PMID- 24572759
TI  - Lumbar segmental instability fact or fiction?

PMID- 24572758
TI  - Non-pharmacologic Control of Pain in HIV / AIDS.

PMID- 24572761
TI  - Adaptive evolution of the circadian gene timeout in insects.
AB  - Most insects harbor two paralogous circadian genes, namely timeout and timeless.
      However, in the Hymenoptera only timeout is present. It remains unclear whether
      both genes, especially timeout in hymenopteran insects, have distinct
      evolutionary patterns. In this study, we examine the molecular evolution of both
      genes in 25 arthropod species, for which whole genome data are available, with
      addition of the daily expression of the timeout gene in a pollinating fig wasp,
      Ceratosolen solmsi (Hymenoptera: Chalcidoidea: Agaonidae). Timeless is under
      stronger purifying selection than timeout, and timeout has positively selected
      sites in insects, especially in the Hymenoptera. Within the Hymenoptera, the
      function of timeout may be conserved in bees and ants, but still evolving rapidly
      in some wasps such as the chalcids. In fig wasps, timeout is rhythmically
      expressed only in females when outside of the fig syconium but arrhythmically in
      male and female wasps inside the syconium. These plastic gene expressions reflect
      adaptive differences of males and females to their environment. 

PMID- 24572762
TI  - Dabigatran-induced lupus temporarily preventing blood group determination.
AB  - Epistaxis resulted in severe anemia in an 89-year-old Caucasian woman under a
      therapy with dabigatran for 12 months because of atrial fibrillation. Correction
      of the anemia was difficult because it was impossible to assess her blood group
      due to polyagglutination. Since hospital records disclosed that in 2011, her
      blood group was O positive, acquired polyagglutination was assumed. After 66
      days, it was again possible to assess the blood group as O positive. Immunologic
      investigations disclosed that antinuclear antibodies and antihistone antibodies
      were elevated, and antibodies to double-stranded DNA were negative. Drug-induced
      lupus was diagnosed due to the autoantibody profile detected. 

PMID- 24572765
TI  - An infinite square lattice of super-supertetrahedral T(6)-like tin oxyselenide
      clusters.
AB  - A new super-supertetrahedral cluster, resembling a coreless supertetrahedral T6
      cluster, was made as a tin oxyselenide by integrating hard and soft Lewis bases
      (O(2-) and Se(2-)) into the tetravalent system. Its hierarchical architecture,
      built from supertetrahedral T3-[Sn10O4Se20] and Sn2Se6 clusters, represents a new
      level of complexity in the cluster-based construction. Compared to pure tin
      selenides, the new tin oxyselenide material in this work shows much enhanced
      stability and size-dependent band energy level. 

PMID- 24572766
TI  - A series of rare earth complexes with novel non-interpenetrating 3D networks:
      synthesis, structures, magnetic and optical properties.
AB  - A series of metal-organic framework {Ln(BCPBA)(H2O)}n {Ln = Nd (1), Sm (2), Eu
      (3), Tb (4), Dy (5)}; {[Ln(BCPBA)(H2O)](H2O)}n {Ln = Pr (6), Gd (7)} have been
      synthesized through the hydrothermal synthesis method. These compounds possess
      non-interpenetrating 3D networks with 10.1438 A* 17.9149 A rhombic channels along
      the [001] direction. The results of temperature-dependent magnetic susceptibility
      measurements indicate that compounds 4 and 7 exhibit Ln(III)Ln(III)
      antiferromagnetic interactions, while compound 5 exhibits Ln(III)Ln(III)
      ferromagnetic interactions. Frequency dependent out-of-phase signals were
      observed in alternating current (ac) magnetic susceptibility measurements which
      indicate that they have slow magnetic relaxation characteristics. The luminescent
      properties of 1, 2, 3, 4, and 5 are also discussed. Due to the good match between
      the lowest triplet state of the ligand and the resonant energy level of the
      lanthanide ion, compound 4 has longer fluorescence lifetime (tau1 = 400.0000 ms,
      tau2 = 1143.469 ms) and higher quantum yield (Phi = 42%) compared with other
      compounds. 

PMID- 24572763
TI  - Identification of volatile organic compounds in human cerumen.
AB  - We report here the initial examination of volatile organic compounds (VOCs)
      emanating from human earwax (cerumen). Recent studies link a single nucleotide
      polymorphism (SNP) in the adenosine triphosphate (ATP) binding cassette, sub
      family C, member 11 gene (ABCC11) to the production of different types of
      axillary odorants and cerumen. ABCC11 encodes an ATP-driven efflux pump protein
      that plays an important function in ceruminous apocrine glands of the auditory
      canal and the secretion of axillary odor precursors. The type of cerumen and
      underarm odor produced by East Asians differ markedly from that produced by non
      Asians. In this initial report we find that both groups emit many of the same
      VOCs but differ significantly in the amounts produced. The principal odorants are
      volatile organic C2-to-C6 acids. The physical appearance of cerumen from the two
      groups also matches previously reported ethnic differences, viz., cerumen from
      East Asians appears dry and white while that from non-Asians is typically wet and
      yellowish-brown. 

PMID- 24572764
TI  - Omics approaches in food safety: fulfilling the promise?
AB  - Genomics, transcriptomics, and proteomics are rapidly transforming our approaches
      to the detection, prevention, and treatment of foodborne pathogens. Microbial
      genome sequencing in particular has evolved from a research tool into an approach
      that can be used to characterize foodborne pathogen isolates as part of routine
      surveillance systems. Genome sequencing efforts will not only improve outbreak
      detection and source tracking, but will also create large amounts of foodborne
      pathogen genome sequence data, which will be available for data-mining efforts
      that could facilitate better source attribution and provide new insights into
      foodborne pathogen biology and transmission. Although practical uses and
      application of metagenomics, transcriptomics, and proteomics data and associated
      tools are less prominent, these tools are also starting to yield practical food
      safety solutions. 

PMID- 24572767
TI  - In patients with extensive subcutaneous emphysema, which technique achieves
      maximal clinical resolution: infraclavicular incisions, subcutaneous drain
      insertion or suction on in situ chest drain?
AB  - A best evidence topic in cardiac surgery was written according to a structured
      protocol. The question addressed was: 'In patients with extensive subcutaneous
      emphysema, which technique achieves maximal clinical resolution: infraclavicular
      incisions, subcutaneous drain insertion or suction on in situ chest drain?'.
      Altogether more than 200 papers were found using the reported search, of which 14
      represented the best evidence to answer the clinical question. The authors,
      journal, date and country of publication, patient group studied, study type,
      relevant outcomes and results of these papers are tabulated. Subcutaneous
      emphysema is usually a benign, self-limiting condition only requiring
      conservative management. Interventions are useful in the context of severe
      patient discomfort, respiratory distress or persistent air leak. In the absence
      of any comparative study, it is not possible to choose definitively between
      infraclavicular incisions, drain insertion and increasing suction on an in situ
      drain as the best method for managing severe subcutaneous emphysema. All the
      three techniques described have been shown to provide effective relief.
      Increasing suction on a chest tube already in situ provided rapid relief in
      patients developing SE following pulmonary resection. A retrospective study
      showed resolution in 66%, increasing to 98% in those who underwent video-assisted
      thoracic surgery with identification and closure of the leak. Insertion of a
      drain into the subcutaneous tissue also provided rapid sustained relief. Several
      studies aided drainage by using regular compressive massage. Infraclavicular
      incisions were also shown to provide rapid relief, but were noted to be more
      invasive and carried the potential for cosmetic defect. No major complications
      were illustrated.

PMID- 24572768
TI  - Extraction bag lavage cytology during video-assisted thoracoscopic surgery for
      primary lung cancer.
AB  - OBJECTIVES: Sample extraction from the thoracic cavity through an intercostal
      space during video-assisted thoracoscopic surgery can result in cancer cell
      contamination by tumour crushing and tumour cell extravasation, and may have
      adverse effects on the surgical outcome. Lavage cytology of the sample extraction
      bag was investigated to clarify the risk of cancer cell spillage and identify the
      clinicopathological features associated with susceptibility to cancer cell
      spillage during extraction. METHODS: Lavage cytology of the sample extraction bag
      was investigated in 464 patients with negative pleural lavage cytology who
      underwent lung resection for primary lung cancer via video-assisted thoracoscopic
      surgery between January 2010 and December 2012. The surgical procedures,
      pathological findings and clinical course were evaluated by hospital record
      review. RESULTS: The incidence of positive bag lavage cytology (BLC) was 13.6%.
      Statistically significant factors associated with susceptibility to BLC
      positivity were tumour size, standardized uptake value of positron emission
      tomography, pathological features such as pathological N score, pleural invasion,
      vascular invasion and papillary-predominant adenocarcinoma. Among patients with
      Stage I lung cancer, the survival rate was significantly lower in the BLC
      positive group than in the BLC-negative group. CONCLUSIONS: BLC positivity can be
      related to oncological characteristics such as tumour invasiveness and
      adhesiveness as opposed to tumour size and surgical margin, and may help to
      determine the prognosis of Stage I lung cancer. The sample extraction bag must be
      carefully manoeuvred through the intercostal space to prevent cancer cell
      dissemination to the chest wall or thoracic cavity.

PMID- 24572770
TI  - The relationship between classification of multi-domain proteins using an
      alignment-free approach and their functions: a case study with immunoglobulins.
AB  - Establishing functional relationships between multi-domain protein sequences is a
      non-trivial task. Traditionally, delineating functional assignment and
      relationships of proteins requires domain assignments as a prerequisite. This
      process is sensitive to alignment quality and domain definitions. In multi-domain
      proteins due to multiple reasons, the quality of alignments is poor. We report
      the correspondence between the classification of proteins represented as full
      length gene products and their functions. Our approach differs fundamentally from
      traditional methods in not performing the classification at the level of domains.
      Our method is based on an alignment free local matching scores (LMS) computation
      at the amino-acid sequence level followed by hierarchical clustering. As there
      are no gold standards for full-length protein sequence classification, we
      resorted to Gene Ontology and domain-architecture based similarity measures to
      assess our classification. The final clusters obtained using LMS show high
      functional and domain architectural similarities. Comparison of the current
      method with alignment based approaches at both domain and full-length protein
      showed superiority of the LMS scores. Using this method we have recreated
      objective relationships among different protein kinase sub-families and also
      classified immunoglobulin containing proteins where sub-family definitions do not
      exist currently. This method can be applied to any set of protein sequences and
      hence will be instrumental in analysis of large numbers of full-length protein
      sequences. 

PMID- 24572769
TI  - Assessment of results of surgical treatment for persistent atrial fibrillation
      during coronary artery bypass grafting using implantable loop recorders.
AB  - OBJECTIVES: We report our experience with a modified mini-maze procedure and
      pulmonary vein isolation using radiofrequency energy for treating persistent
      atrial fibrillation during coronary artery bypass grafting (CABG). METHODS:
      Ninety-five patients with persistent atrial fibrillation and coronary heart
      disease underwent open heart surgery combined with intraoperative irrigated
      radiofrequency ablation. Patients were randomized into the following three
      groups: CABG and irrigated radiofrequency pulmonary vein isolation (CABG+PVI, n =
      31); CABG and an irrigated radiofrequency modified mini-maze procedure (CABG+MM,
      n = 30); and isolated CABG (CABG alone, n = 34). All patients received
      implantable loop recorders. RESULTS: No reoperation and no hospital mortality
      were recorded. Mean follow-up was 14.4 +/- 9.7 months. The implantable loop
      recorder-determined freedom from atrial fibrillation was 80% in the CABG+PVI
      group, 86.2% in the CABG+MM group and 44.1% in the CABG alone group. CONCLUSIONS:
      Patients with concomitant atrial fibrillation and coronary heart disease may
      benefit from intraoperative ablation to prevent relapse of arrhythmia.

PMID- 24572771
TI  - Non-reciprocal and highly nonlinear active acoustic metamaterials.
AB  - Unidirectional devices that pass acoustic energy in only one direction have
      numerous applications and, consequently, have recently received significant
      attention. However, for most practical applications that require
      unidirectionality at audio and low frequencies, subwavelength implementations
      capable of the necessary time-reversal symmetry breaking remain elusive. Here we
      describe a design approach based on metamaterial techniques that provides highly
      subwavelength and strongly non-reciprocal devices. We demonstrate this approach
      by designing and experimentally characterizing a non-reciprocal active acoustic
      metamaterial unit cell composed of a single piezoelectric membrane augmented by a
      nonlinear electronic circuit, and sandwiched between Helmholtz cavities tuned to
      different frequencies. The design is thinner than a tenth of a wavelength, yet it
      has an isolation factor of >10 dB. The design method generates relatively
      broadband unidirectional devices and is a good candidate for numerous acoustic
      applications. 

PMID- 24572772
TI  - Lower kinetic chain and human gait.

PMID- 24572773
TI  - Contributing factors in microtrauma injuries of the lower extremity.

PMID- 24572774
TI  - Microtrauma injuries and rehabilitation of the foot and ankle.

PMID- 24572775
TI  - The application of open and closed kinematic chain exercises in rehabilitation of
      the lower extremity.

PMID- 24572776
TI  - Clinical decision making for biomechanical foot orthoses.

PMID- 24572777
TI  - Indications for Referral: Orthotist, Physical Therapist, Podiatrist-What's the
      Difference?

PMID- 24572778
TI  - Radiographic evaluation of ankle trauma.

PMID- 24572779
TI  - Magnetic resonance and related modalities used to image osteonecrosis of the hip.

PMID- 24572782
TI  - Introduction.

PMID- 24572783
TI  - Intracisternal delivery of AAV9 results in oligodendrocyte and motor neuron
      transduction in the whole central nervous system of cats.
AB  - Systemic and intracerebrospinal fluid delivery of adeno-associated virus serotype
      9 (AAV9) has been shown to achieve widespread gene delivery to the central
      nervous system (CNS). However, after systemic injection, the neurotropism of the
      vector has been reported to vary according to age at injection, with greater
      neuronal transduction in newborns and preferential glial cell tropism in adults.
      This difference has not yet been reported after cerebrospinal fluid (CSF)
      delivery. The present study analyzed both neuronal and glial cell transduction in
      the CNS of cats according to age of AAV9 CSF injection. In both newborns and
      young cats, administration of AAV9-GFP in the cisterna magna resulted in high
      levels of motor neurons (MNs) transduction from the cervical (84+/-5%) to the
      lumbar (99+/-1%) spinal cord, demonstrating that the remarkable tropism of AAV9
      for MNs is not affected by age at CSF delivery. Surprisingly, numerous
      oligodendrocytes were also transduced in the brain and in the spinal cord white
      matter of young cats, but not of neonates, indicating that (i) age of CSF
      delivery influences the tropism of AAV9 for glial cells and (ii) AAV9
      intracisternal delivery could be relevant for both the treatment of MN and
      demyelinating disorders. 

PMID- 24572784
TI  - MULT1E/mIL-12: a novel bifunctional protein for natural killer cell activation.
AB  - Natural killer (NK) cells have the potential to be effective killers of tumor
      cells. They are governed by inhibitory and activating receptors like NKG2D, whose
      ligands are normally upregulated in cells that are stressed, like cancer cells.
      Advanced cancer cells, however, have ways to reduce these ligands' expression,
      leaving them less detectable by NK cells. Along with these receptors, NK cells
      also require activating cytokines, like interleukin 12 (IL-12). The goal of this
      study is to develop a novel bi-functional fusion protein for enhanced NK cell
      activation. The proposed protein combines the extracellular domain of the NKG2D
      ligand Mouse UL-16-binding protein-like transcript 1 (MULT1E) and mouse IL-12
      (mIL-12). It is hypothesized that when expressed by tumor cells, the protein will
      activate NK and other killer cells using the NKG2D receptor, and deliver mIL-12
      to the NK cells where it can interact with the IL-12R and enhance cytotoxicity.
      The fusion protein, when expressed by engineered tumor cells, indeed activated NK
      cells in vitro as assayed by increased production of interferon-gamma and
      cytotoxicity and significantly reduced tumor growth in vivo. Although the study
      is preliminary, the data suggest that the MULT1E/mIL-12 bi-functional fusion
      protein is an effective activator of NK cells for cancer treatment. 

PMID- 24572785
TI  - Gene therapy for trigeminal pain in mice.
AB  - The aim of this study was to test the efficacy of a single direct injection of
      viral vector encoding for encephalin to induce a widespread expression of the
      transgene and potential analgesic effect in trigeminal behavioral pain models in
      mice. After direct injection of herpes simplex virus type 1 based vectors
      encoding for human preproenkephalin (SHPE) or the lacZ reporter gene (SHZ.1,
      control virus) into the trigeminal ganglia in mice, we performed an orofacial
      formalin test and assessed the cumulative nociceptive behavior at different time
      points after injection of the viral vectors. We observed an analgesic effect on
      nociceptive behavior that lasted up to 8 weeks after a single injection of SHPE
      into the trigeminal ganglia. Control virus-injected animals showed nociceptive
      behavior similar to naive mice. The analgesic effect of SHPE injection was
      reversed/attenuated by subcutaneous naloxone injections, a MU-opioid receptor
      antagonist. SHPE-injected mice also showed normalization in withdrawal latencies
      upon thermal noxious stimulation of inflamed ears after subdermal complete
      Freund's adjuvant injection, indicating widespread expression of the transgene.
      Quantitative immunohistochemistry of trigeminal ganglia showed expression of
      human preproenkephalin after SHPE injection. Direct injection of viral vectors
      proved to be useful for exploring the distinct pathophysiology of the trigeminal
      system and could also be an interesting addition to the pain therapists'
      armamentarium. 

PMID- 24572787
TI  - Sonic hedgehog gene therapy increases the ability of the dystrophic skeletal
      muscle to regenerate after injury.
AB  - The Hedgehog (Hh) pathway is a crucial regulator of muscle development during
      embryogenesis. We have previously demonstrated that Sonic hedgehog (Shh)
      regulates postnatal myogenesis in the adult skeletal muscle both directly, by
      acting on muscle satellite cells, and indirectly, by promoting the production of
      growth factors from interstitial fibroblasts. Here, we show that in mdx mice, the
      murine equivalent of Duchenne muscular dystrophy in humans, progression of the
      dystrophic pathology corresponds to progressive inhibition of the Hh signaling
      pathway in the skeletal muscle. We also show that the upregulation of the Hh
      pathway in response to injury and during regeneration is significantly impaired
      in mdx muscle. Shh treatment increases the proliferative potential of satellite
      cells isolated from the muscles of mdx mice. This treatment also increases the
      production of proregenerative factors, such as insulin-like growth factor-1 and
      vascular endothelial growth factor, from fibroblasts isolated from the muscle of
      mdx mice. In vivo, overexpression of the Hh pathway using a plasmid encoding the
      human Shh gene promotes successful regeneration after injury in terms of
      increased number of proliferating myogenic cells and newly formed myofibers, as
      well as enhanced vascularization and decreased fibrosis. 

PMID- 24572788
TI  - Long-term correction of biochemical and neurological abnormalities in MLD mice
      model by neonatal systemic injection of an AAV serotype 9 vector.
AB  - As both the immune system and the blood-brain barrier (BBB) are likely to be
      developmentally immature in the perinatal period, neonatal gene transfer may be
      useful for the treatment of lysosomal storage disease (LSD) with neurological
      involvements such as metachromatic leukodystrophy (MLD). In this experiment, we
      examined the feasibility of single-strand adeno-associated viral serotype-9
      (ssAAV9)-mediated systemic neonatal gene therapy of MLD mice. ssAAV9 vector
      expressing human arylsulfatase A (ASA) and green fluorescent protein (GFP)
      (ssAAV9/ASA) was injected into the jugular vein of newborn MLD mice. High levels
      of ASA expression were observed in the muscle and heart for at least 15 months.
      ASA was continuously secreted into plasma without development of antibodies
      against ASA. Global gene transfer into the brain and spinal cord (SC), across the
      BBB, and long-term ASA expression in the central nervous system were detected in
      treated mice. Significant inhibition of the accumulation of sulfatide (Sulf) in
      the brain and cervical SC was confirmed by Alcian blue staining and biochemical
      analysis of the Sulf content. In a behavior test, treated mice showed a greater
      ability to traverse narrow balance beams than untreated mice. These data clearly
      demonstrate that MLD mice model can be effectively treated through neonatal
      systemic injection of ssAAV9/ASA. 

PMID- 24572786
TI  - Effect of bortezomib on the efficacy of AAV9.SERCA2a treatment to preserve
      cardiac function in a rat pressure-overload model of heart failure.
AB  - Adeno-associated virus (AAV)-based vectors are promising vehicles for therapeutic
      gene delivery, including for the treatment for heart failure. It has been
      demonstrated for each of the AAV serotypes 1 through 8 that inhibition of the
      proteasome results in increased transduction efficiencies. For AAV9, however, the
      effect of proteasome inhibitors on in vivo transduction has until now not been
      evaluated. Here we demonstrate, in a well-established rodent heart failure model,
      that concurrent treatment with the proteasome inhibitor bortezomib does not
      enhance the efficacy of AAV9.SERCA2a to improve cardiac function as examined by
      echocardiography and pressure volume analysis. Western blot analysis of SERCA2a
      protein and reverse transcription-PCR of SERCA2a mRNA demonstrated that
      bortezomib had no effect on either endogenous rat SERCA2a levels nor on
      expression levels of human SERCA2a delivered by AAV9.SERCA2a. Similarly, the
      number of AAV9 genomes in heart samples was unaffected by bortezomib treatment.
      Interestingly, whereas transduction of HeLa cells and neonatal rat cardiomyocytes
      by AAV9 was stimulated by bortezomib, transduction of adult rat cardiomyocytes
      was inhibited. These results indicate an organ/cell-type-specific effect of
      proteasome inhibition on AAV9 transduction. A future detailed analysis of the
      underlying molecular mechanisms promises to facilitate the development of
      improved AAV vectors. 

PMID- 24572790
TI  - Tumor-associated antigen/IL-21-transduced dendritic cell vaccines enhance
      immunity and inhibit immunosuppressive cells in metastatic melanoma.
AB  - Dendritic cell (DC)-based vaccine approaches are being actively evaluated for
      developing immunotherapeutic agents against cancers. In this study, we
      investigated the use of engineered DCs expressing transgenic tumor-associated
      antigen hgp100 and the regulatory cytokine interleukin-21, namely DC-hgp100/mIL
      21, as a therapeutic vaccine against melanoma. Tumor-bearing mice were injected
      intratumorally with transgenic DCs followed by three booster injections.
      Transgenic DC-hgp100/mIL-21 showed significant reduction in primary tumor growth
      and metastasis compared with DC-hgp100 alone and DC-mIL-21 alone. In vivo
      depletion of specific immune cell types (CD8(+) T, CD4(+) T and Natural killer
      (NK)-1.1(+) cells) effectively blocked the protective effect of this
      combinational vaccine. In adoptive transfer experiments, a survival rate of
      nearly 90% was observed at 60 days post-tumor inoculation for the combinational
      vaccine group. In contrast, all mice in the DC-hgp100 and DC-mIL-21-only groups
      died within 43-46 days after tumor challenge. Considerably increased levels of
      interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, granulocyte macrophage
      colony-stimulating factor (GM-CSF) and cytotoxic T lymphocytes (CTLs) were
      detected with the combination vaccine group compared with other individual
      treatment groups. In comparison with the DC-hgp100 or mIL-21 groups, the
      combinational DC-hgp100/mIL-21 vaccine also drastically suppressed the myeloid
      derived suppressor cells (MDSCs) and T-regulatory (Treg) cell populations. Our
      findings suggest that a combinational DC- and gene-based hgp100 and mIL-21
      vaccine therapy strategy warrants further evaluation as a clinically relevant
      cancer vaccine approach for human melanoma patients. 

PMID- 24572789
TI  - Vaccination with tumor cells expressing IL-15 and IL-15Ralpha inhibits murine
      breast and prostate cancer.
AB  - A number of antitumor vaccines have recently shown promise in upregulating immune
      responses against tumor antigens and improving patient survival. In this study,
      we examine the effectiveness of vaccination using interleukin (IL)-15-expressing
      tumor cells and also examine their ability to upregulate immune responses to
      tumor antigens. We demonstrated that the coexpression of IL-15 with its receptor,
      IL-15Ralpha, increased the cell-surface expression and secretion of IL-15. We
      show that a gene transfer approach using recombinant adenovirus to express IL-15
      and IL-15Ralpha in murine TRAMP-C2 prostate or TS/A breast tumors induced
      antitumor immune responses. From this, we developed a vaccine platform,
      consisting of TRAMP-C2 prostate cancer cells or TS/A breast cancer cells
      coexpressing IL-15 and IL-15Ralpha that inhibited tumor formation when mice were
      challenged with tumor. Inhibition of tumor growth led to improved survival when
      compared with animals receiving cells expressing IL-15 alone or unmodified tumor
      cells. Animals vaccinated with tumor cells coexpressing IL-15 and IL-15Ralpha
      showed greater tumor infiltration with CD8(+) T and natural killer (NK) cells, as
      well as increased antitumor CD8(+) T-cell responses. Vaccination with IL-15/IL
      15Ralpha-modified TS/A breast cancer cells provided a survival advantage to mice
      challenged with unrelated murine TUBO breast cancer cells, indicating the
      potential for allogeneic IL-15/IL-15Ralpha-expressing vaccines. 

PMID- 24572791
TI  - Gene transfer of arginine kinase to skeletal muscle using adeno-associated virus.
AB  - In this study, we tested the feasibility of non-invasively measuring
      phosphoarginine (PArg) after gene delivery of arginine kinase (AK) using an adeno
      associated virus (AAV) to murine hindlimbs. This was achieved by evaluating the
      time course, regional distribution and metabolic flux of PArg using
      (31)phosphorus magnetic resonance spectroscopy ((31)P-MRS). AK gene was injected
      into the gastrocnemius of the left hindlimb of C57Bl10 mice (age 5 weeks, male)
      using self-complementary AAV, type 2/8 with desmin promoter. Non-localized (31)P
      MRS data were acquired over 9 months after injection using 11.1-T and 17.6-T
      Bruker Avance spectrometers. In addition, (31)P two-dimensional chemical shift
      imaging and saturation transfer experiments were performed to examine the spatial
      distribution and metabolic flux of PArg, respectively. PArg was evident in each
      injected mouse hindlimb after gene delivery, increased until 28 weeks, and
      remained elevated for at least 9 months (P<0.05). Furthermore, PArg was primarily
      localized to the injected posterior hindimb region and the metabolite was in
      exchange with ATP. Overall, the results show the viability of AAV gene transfer
      of AK gene to skeletal muscle, and provide support of PArg as a reporter that can
      be used to non-invasively monitor the transduction of genes for therapeutic
      interventions. 

PMID- 24572794
TI  - The morbidity and mortality linked to melancholia: two cohorts compared, 1875
      1924 and 1995-2005.
AB  - For over a century, melancholia has been linked to increased rates of morbidity
      and mortality. Data from two epidemiologically complete cohorts of patients
      presenting to mental health services in North Wales (1874-1924 and 1995-2005)
      have been used to look at links between diagnoses of melancholia in the first
      period and severe hospitalized depressive disorders today and other illnesses,
      and to calculate mortality rates. This is a study of the hospitalized illness
      rather than the natural illness, and the relationship between illness and
      hospitalization remains poorly understood. These data confirm that melancholia is
      associated with a substantial increase in the standardized mortality rate both
      formerly and today, stemming from a higher rate of deaths from tuberculosis in
      the historical sample and from suicide in the contemporary sample. The data do
      not link melancholia to cancer or cardiac disease. The comparison between
      outcomes for melancholia historically and severe mood disorder today argue
      favourably for the effectiveness of asylum care. 

PMID- 24572795
TI  - Ergotism in Norway. Part 1: The symptoms and their interpretation from the late
      Iron Age to the seventeenth century.
AB  - Ergotism is a horrendous disease with grotesque symptoms caused by ingesting
      specific ergot alkaloids. Mass poisoning episodes are attributable to consumption
      of grain - usually rye - infected with the fungus Claviceps purpurea. By focusing
      on possible cases of ergotism, we re-examine Norwegian history from the sagas
      through to the end of the seventeenth century. Our review - not intended to be
      exhaustive, or ex post facto to assign medical or psychiatric labels - draws
      attention to the very real possibility that many remarkable medical cases may
      have been the result of the ingestion of highly poisonous and psychoactive food
      substances. Where possible we highlight explanations given at the time - often
      rooted in religion or demonology - to explain the disease. 

PMID- 24572792
TI  - Efficient delivery of lentiviral vectors into resting human CD4 T cells.
AB  - Resting human CD4 T cells are highly resistant to transfection or infection with
      lentiviral vectors derived from the human immunodeficiency virus. We now describe
      a flexible and efficient approach involving virus-like particles containing
      simian immunodeficiency virus lentiviral gene product protein X and pseudotyping
      with CXCR4-tropic HIV Env. This method permits effective genetic manipulation of
      these cells while preserving their naturally quiescent state. This technology can
      also be extended to primary lymphoid cultures where authentic cellular
      composition and functional relationships are preserved. 

PMID- 24572793
TI  - Efficient gene delivery to the cone-enriched pig retina by dual AAV vectors.
AB  - Gene therapy with adeno-associated viral (AAV) vectors is limited by AAV cargo
      capacity that prevents their application to the inherited retinal diseases
      (IRDs), such as Stargardt disease (STGD) or Usher syndrome type IB (USH1B), which
      are due to mutations in genes larger than 5 kb. Trans-splicing or hybrid dual AAV
      vectors have been successfully exploited to reconstitute large gene expression in
      the mouse retina. Here, we tested them in the large cone-enriched pig retina that
      closely mimics the human retina. We found that dual AAV trans-splicing and hybrid
      vectors transduce pig photoreceptors, the major cell targets for treatment of
      IRDs, to levels that were about two- to threefold lower than those obtained with
      a single AAV vector of normal size. This efficiency is significantly higher than
      that in mice, and is potentially due to the high levels of dual AAV co
      transduction we observe in pigs. We also show that subretinal delivery in pigs of
      dual AAV trans-splicing and hybrid vectors successfully reconstitute, albeit at
      variable levels, the expression of the large genes ABCA4 and MYO7A mutated in
      STGD and USH1B, respectively. Our data support the potential of dual AAV vectors
      for large gene reconstitution in the cone-enriched pig retina that is a relevant
      preclinical model. 

PMID- 24572796
TI  - Revisiting mental hygiene: Josef Lundahl's interpretation of modern psychiatry in
      Sweden at the beginning of the twentieth century.
AB  - The concept of mental hygiene is historically intertwined with eugenics and what
      it meant both ideologically and for the care of the mentally ill. A closer
      investigation of the concept and of the historical context shows that different
      interpretations existed simultaneously. The aim of this essay is to highlight the
      literary and scientific works of a Swedish psychiatrist, Josef Lundahl, an
      advocate of the mental hygiene concept. A close reading of his texts is used to
      provide an example of how the concept of mental hygiene was understood by a
      psychiatrist and practitioner of mental hygiene. The practice of child-care and
      out-patient care that Lundahl founded in Visby is far from what we now associate
      with mental hygiene in the past. 

PMID- 24572797
TI  - Psychopathology beyond semiology. An essay on the inner workings of
      psychopathology.
AB  - This text develops three interwoven issues: first, a succinct comparative
      analysis of medical and psychiatric semiology, which proposes that the lack of
      referring relations between psychiatric symptoms and brain/psychic dysfunction is
      a fundamental distinction between medical and psychiatric semiology. Second, the
      multiple features of psychiatric semiology are reviewed. Third, a new approach to
      psychopathology is introduced, proposing three different ways to shape symptoms
      (perception, linguistic structure, praxis); highlighting its role as a cognitive
      activity that creates intelligibility from undifferentiated experiences; and
      distinguishing psychopathology and semiology on an activity/product relation
      basis. 

PMID- 24572798
TI  - William James and psychical research: towards a radical science of mind.
AB  - Traditional textbooks on the history of psychiatry and psychology fail to
      recognize William James's investigations on psychic phenomena as a legitimate
      effort to understand the human mind. The purpose of this paper is to offer
      evidence of his views regarding the exploration of those phenomena as well as the
      radical, yet alternative, solutions that James advanced to overcome theoretical
      and methodological hindrances. Through an analysis of his writings, it is argued
      that his psychological and philosophical works converge in psychical research
      revealing the outline of a science of mind capable of encompassing psychic
      phenomena as part of human experience and, therefore, subject to scientific
      scrutiny. 

PMID- 24572800
TI  - Use and abuse of alcohol and other drugs during the heroic age of Antarctic
      exploration.
AB  - During the heroic age of Antarctic exploration, there was much discussion on the
      role of alcohol. The explorers expected to be able to consume alcohol, and the
      expeditions were supported by companies producing alcoholic beverages that used
      the Antarctic connection in their advertising. On the other side, it was said
      (incorrectly) than Fridjof Nansen, perhaps the most famous of the Arctic
      explorers, had taken no alcohol and this was used in the arguments against
      alcohol by the temperance movement. In general, alcohol consumption was low but
      it was felt that alcohol played an important role in maintaining the
      psychological welfare of the participants. A number of them had alcohol problems,
      and participation in an expedition was thought to be of benefit in that it would
      remove the temptation to consume alcohol. However, there were episodes of
      drunkenness on the ships and in the Antarctic. Cocaine was taken as one of a
      number of tonics but only one explorer is thought to have abused drugs, though
      another is said to have done so. 

PMID- 24572799
TI  - 'Paralysed with fears and worries': neurasthenia as a gender-specific disease of
      civilization.
AB  - Around 1900 neurasthenia received much attention in both the medical world and
      society at large. Based on professional publications by Dutch psychiatrists and
      neurologists and on patient records from the Rhijngeest sanatorium near Leiden in
      the Netherlands, this article addresses the meanings and interpretations of this
      nervous disorder as put forward by doctors and patients. We argue that their
      understanding of this disorder was determined not only by medical views, but also
      by social-cultural factors and prevailing gender norms. 

PMID- 24572801
TI  - 'On the Diseases of the Head' in the Scale of Medicine by Muhammad Akbar Arzani
      [d. 1722].
AB  - This Classic Text examines the Mizan-e Tibb (Scale of Medicine), an influential
      medical text by Muhammad Akbar Arzani which circulated widely throughout South
      Asia. The success of Arzani's text rests in its simple prose and the translation
      of Graeco-Arabic medical knowledge into Persian, the language of educated
      discourse throughout South Asia. His chapter 'Dar Amra-e Ras' (On the Diseases of
      the Head) presents the classification and treatment of neuropsychiatric disorders
      within South Asian, Islamic medicine. The excerpt below is taken from a
      critically edited text published in 2001 in Iran. 

PMID- 24572807
TI  - Retrospective diagnosis and its vicissitudes.

PMID- 24572808
TI  - A stem-loop structure directs oskar mRNA to microtubule minus ends.
AB  - mRNA transport coupled with translational control underlies the intracellular
      localization of many proteins in eukaryotic cells. This is exemplified in
      Drosophila, where oskar mRNA transport and translation at the posterior pole of
      the oocyte direct posterior patterning of the embryo. oskar localization is a
      multistep process. Within the oocyte, a spliced oskar localization element (SOLE)
      targets oskar mRNA for plus end-directed transport by kinesin-1 to the posterior
      pole. However, the signals mediating the initial minus end-directed, dynein
      dependent transport of the mRNA from nurse cells into the oocyte have remained
      unknown. Here, we show that a 67-nt stem-loop in the oskar 3' UTR promotes oskar
      mRNA delivery to the developing oocyte and that it shares functional features
      with the fs(1)K10 oocyte localization signal. Thus, two independent cis-acting
      signals, the oocyte entry signal (OES) and the SOLE, mediate sequential dynein-
      and kinesin-dependent phases of oskar mRNA transport during oogenesis. The OES
      also promotes apical localization of injected RNAs in blastoderm stage embryos,
      another dynein-mediated process. Similarly, when ectopically expressed in
      polarized cells of the follicular epithelium or salivary glands, reporter RNAs
      bearing the oskar OES are apically enriched, demonstrating that this element
      promotes mRNA localization independently of cell type. Our work sheds new light
      on how oskar mRNA is trafficked during oogenesis and the RNA features that
      mediate minus end-directed transport. 

PMID- 24572809
TI  - Polypyrimidine tract binding protein inhibits IgM pre-mRNA splicing by diverting
      U2 snRNA base-pairing away from the branch point.
AB  - The mouse immunoglobulin (IgM) pre-mRNA contains a splicing inhibitor that bears
      multiple binding sites for the splicing repressor polypyrimidine tract binding
      protein (PTB). Here we show that the inhibitor directs assembly of an ATP
      dependent complex that contains PTB and U1 and U2 small nuclear RNAs (snRNAs).
      Unexpectedly, although U2 snRNA is present in the inhibitor complex, it is not
      base-paired to the branch point. We present evidence that inhibitor-bound PTB
      contacts U2 snRNA to promote base-pairing to an adjacent branch point-like
      sequence within the inhibitor, thereby preventing the U2 snRNA-branch point
      interaction and resulting in splicing repression. Our studies reveal a novel
      mechanism by which PTB represses splicing. 

PMID- 24572811
TI  - Distinct functional classes of ram mutations in 16S rRNA.
AB  - During decoding, the ribosome selects the correct (cognate) aminoacyl-tRNA (aa
      tRNA) from a large pool of incorrect aa-tRNAs through a two-stage mechanism. In
      the initial selection stage, aa-tRNA is delivered to the ribosome as part of a
      ternary complex with elongation factor EF-Tu and GTP. Interactions between codon
      and anticodon lead to activation of the GTPase domain of EF-Tu and GTP
      hydrolysis. Then, in the proofreading stage, aa-tRNA is released from EF-Tu and
      either moves fully into the A/A site (a step termed "accommodation") or
      dissociates from the ribosome. Cognate codon-anticodon pairing not only
      stabilizes aa-tRNA at both stages of decoding but also stimulates GTP hydrolysis
      and accommodation, allowing the process to be both accurate and fast. In previous
      work, we isolated a number of ribosomal ambiguity (ram) mutations in 16S rRNA,
      implicating particular regions of the ribosome in the mechanism of decoding.
      Here, we analyze a representative subset of these mutations with respect to
      initial selection, proofreading, RF2-dependent termination, and overall miscoding
      in various contexts. We find that mutations that disrupt inter-subunit bridge B8
      increase miscoding in a general way, causing defects in both initial selection
      and proofreading. Mutations in or near the A site behave differently, increasing
      miscoding in a codon-anticodon-dependent manner. These latter mutations may
      create spurious favorable interactions in the A site for certain near-cognate aa
      tRNAs, providing an explanation for their context-dependent phenotypes in the
      cell. 

PMID- 24572810
TI  - Splicing factor hnRNP A2 activates the Ras-MAPK-ERK pathway by controlling A-Raf
      splicing in hepatocellular carcinoma development.
AB  - In recent years, it has become clear that splicing factors play a direct role in
      cancer development. We showed previously that splicing factors SRSF1, SRSF6, and
      hnRNP A2/B1 are up-regulated in several cancers and can act as oncogenes when up
      regulated. Here we examined the role of splicing factors hnRNP A1/A1b and hnRNP
      A2/B1 in hepatocellular carcinoma (HCC). We show that the splicing factors hnRNP
      A1 and hnRNP A2 are up-regulated in HCC tumors derived from inflammation-induced
      liver cancer mouse model. Overexpression of hnRNP A1 or hnRNP A2, but not the
      splicing isoform hnRNP B1, induced tumor formation of immortalized liver
      progenitor cells, while knockdown of these proteins inhibited anchorage
      independent growth and tumor growth of human liver cancer cell lines. In
      addition, we found that cells overexpressing hnRNP A2 showed constitutive
      activation of the Ras-MAPK-ERK pathway. In contrast, knockdown of hnRNP A2
      inhibited the Ras-MAPK-ERK pathway and prevented ERK1/2 activation by EGF.
      Moreover, we found that hnRNP A2 regulates the splicing of A-Raf, reducing the
      production of a short dominant-negative isoform of A-Raf and elevating the full
      length A-Raf transcript. Taken together, our data suggest that hnRNP A2 up
      regulation in HCC induces an alternative splicing switch that down-regulates a
      dominant-negative isoform of A-Raf, leading to activation of the Raf-MEK-ERK
      pathway and cellular transformation. 

PMID- 24572812
TI  - Simple and nonradioactive detection of microRNAs using digoxigenin (DIG)-labeled
      probes with high sensitivity.
AB  - The discovery of microRNAs (miRNAs), which are ~21-23 nucleotides that can
      regulate targeted mRNA by transcript cleavage or protein translation suppression,
      has changed the landscape of biomedical field greatly. At present, Northern blot
      analysis based on radioisotopes is still the most popular method on the detection
      of miRNAs for its high sensitivity. However, radioisotopes have been known for
      certain disadvantages, such as instability, expense, and safety; thus, developing
      a nonradioactive and highly sensitive method is needed. Here, we report a simple,
      nonradioactive, and sensitive method for miRNAs detection based on 5'-phos-3'-DIG
      labeled probes prepared through splinted ligation and EDC cross-linking (DSLE).
      The method was more sensitive than traditional Northern blots with a DIG-labeled
      DNA probe and can detect as low as 2 fmol of miRNAs. The whole procedure can be
      completed within 6-8 h. DSLE method is very convenient, cost-effective, time
      saving, and highly sensitive. 

PMID- 24572813
TI  - Vaccination with the RSV fusion protein formulated with a combination adjuvant
      induces long-lasting protective immunity.
AB  - Respiratory syncytial virus (RSV) is one of the primary causative agents of upper
      and lower respiratory tract infections in young children, in particular infants.
      Recently, we reported the protective efficacy of a RSV vaccine formulation
      consisting of a truncated version of the fusion (F) protein formulated with a
      Toll-like receptor (TLR) agonist and an immunostimulatory peptide in a carrier
      system (DeltaF/TriAdj). To evaluate the duration of immunity induced by this
      vaccine candidate, we carried out long-term trials. The DeltaF was formulated
      with triple adjuvant (TriAdj) containing either polyinosinic : polycytidylic acid
      (polyI : C) or cytosine-phosphate-guanosine oligodeoxynucleotides (CpG ODNs) and
      administered intranasally to mice. One year after the second vaccination all mice
      were challenged with RSV. Both DeltaF/TriAdj formulations mediated the induction
      of high levels of IgG1, IgG2a and virus-neutralizing antibodies, and IgA in the
      lungs. Based on the numbers of IFN-gamma- and IL-5-secreting cells in the spleen,
      the immune response was slightly T-helper cell type 1 (Th1)-biased. This was
      confirmed by the presence of F85-93-specific CD8(+) effector T cells in the lungs
      of both DeltaF/TriAdj(polyI : C)- and DeltaF/TriAdj(CpG)-immunized mice. Both
      DeltaF/TriAdj formulations induced RSV-specific CD8(+) T cells. However,
      DeltaF/TriAdj(polyI : C) generated significantly higher IgG affinity maturation
      and higher numbers of RSV-specific CD8(+) effector memory T cells in lungs and
      CD8(+) central memory T cells in spleen and lymph nodes than DeltaF/TriAdj(CpG).
      After RSV challenge, no virus replication and no evidence of vaccine-induced
      pathology were detected in mice immunized with either of the DeltaF/TriAdj
      formulations, demonstrating that the duration of immunity induced with these
      vaccines is at least one year. 

PMID- 24572814
TI  - Rikkunshito, a Kampo medicine, ameliorates post-operative ileus by anti
      inflammatory action.
AB  - Rikkunshito (RKT), a Kampo (Japanese herbal) medicine, is used as a prokinetic
      for patients with various diseases including functional dyspepsia. RKT promotes
      delayed gastric emptying via 5-HT3 receptor blockade. Otherwise, RKT increases
      ghrelin release via 5-HT2B and 5-HT2C receptor activation. Recent studies
      revealed that ghrelin and 5-HT3 receptor antagonists have an anti-inflammatory
      effect. So we hypothesize that RKT may have an anti-inflammatory action in the
      post-operative ileus. Intestinal manipulation (IM) was applied to the distal
      ileum of mice. RKT was administered orally 4 times before and after IM.
      Gastrointestinal transit in vivo, leukocyte infiltration, and gastric emptying
      were analyzed. We also investigated the effects of the 5-HT3 receptor agonist m
      chlorophenylbiguamide (mCPBG) and ghrelin-receptor antagonist [D-Lys3]-GHRP-6 on
      the ameliorative action of RKT. RKT treatment led to recovery of the delayed
      intestinal transit and gastric emptying rate induced by IM. RKT significantly
      inhibited the infiltration of neutrophils and macrophages. [D-Lys3]-GHRP-6
      reduced and mCPBG partially reduced the RKT-mediated anti-inflammatory activity,
      as monitored by infiltrating macrophages and neutrophils. RKT serves as a novel
      therapeutic agent for POI characterized by its anti-inflammatory potency, in
      addition to prokinetic action. The RKT-induced anti-inflammatory activity may be
      partly mediated by inhibition of the 5-HT3 receptor and ghrelin release.

PMID- 24572815
TI  - Chrono-biology, chrono-pharmacology, and chrono-nutrition.
AB  - The circadian clock system in mammals drives many physiological processes
      including the daily rhythms of sleep-wake behavior, hormonal secretion, and
      metabolism. This system responds to daily environmental changes, such as the
      light-dark cycle, food intake, and drug administration. In this review, we focus
      on the central and peripheral circadian clock systems in response to drugs, food,
      and nutrition. We also discuss the adaptation and anticipation mechanisms of our
      body with regard to clock system regulation of various kinetic and dynamic
      pathways, including absorption, distribution, metabolism, and excretion of drugs
      and nutrients. "Chrono-pharmacology" and "chrono-nutrition" are likely to become
      important research fields in chrono-biological studies. 

PMID- 24572817
TI  - From the editor.

PMID- 24572818
TI  - Thoracic outlet syndrome: An uncommon (even rare) condition trying to find a home
      in industrial injuries.

PMID- 24572816
TI  - Ranolazine attenuates the enhanced reverse Na+-Ca2+ exchange current via
      inhibiting hypoxia-increased late sodium current in ventricular myocytes.
AB  - Ranolazine (RAN), a novel antianginal agent, inhibits the increased late sodium
      current (INa.L) under many pathological conditions. In this study, the whole-cell
      patch-clamp technique was used to explore the effects of RAN on INa.L and reverse
      Na(+)/Ca(2+) exchange current (INCX) in rabbit ventricular myocytes during
      hypoxia.Tetrodotoxin (TTX) at 2 MUM or RAN at 9 MUM decreased significantly INa.L
      and reverse INCX under normoxia and RAN had no further effects on both currents
      in the presence of TTX. RAN (3, 6, and 9 MUM) attenuated hypoxia-increased INa.L
      and reverse INCX in a concentration-dependent manner. Hypoxia-increased INa.L and
      reverse INCX were inhibited by 2 MUM TTX, whereas 9 MUM RAN applied sequentially
      did not further decrease both currents. In another group, after both currents
      were decreased by 9 MUM RAN, 2 MUM TTX had no further effects in the presence of
      Ran. In monophasic action potential (MAP) recording, early after-depolarizations
      (EADs) were suppressed by RAN (9 MUM) during hypoxia. In conclusion, RAN
      decreased reverse INCX by inhibiting INa.L in normoxia, concentration-dependently
      attenuated the increase of INa.L, which thereby decreased the reverse INCX, and
      obviously relieved EADs during hypoxia. 

PMID- 24572819
TI  - Thoracic outlet syndrome: A functional dysfunction of the upper thoracic
      aperture?
AB  - PURPOSE OF THE STUDY: To determine possible malfunction of the upper thoracic
      aperture (an upward displacement of the first rib at the costotransverse joint)
      as the cause of thoracic outlet syndrome (TOS) symptoms among consecutive TOS
      patients admitted for conservative treatment. BASIC PROCEDURES: Fifteen
      consecutive TOS patients, with a positive TOS index, admitted for conservative
      treatment were investigated with a three-dimensional CT scan of the upper
      thoracic aperture. A rehabilitation program was administered at a rehabilitation
      ward. The CT scans were evaluated for a possible upward displacement of the first
      rib at the costotransverse joint. The outcome of conservative therapy was
      classified as good if the patient was symptom free and poor if loading of the
      upper limbs still produced symptoms. Outcome follow-up time was 1 year. MAIN
      FINDINGS: An asymmetry of the first rib was shown on the symptomatic side,
      indicating an upward displacement of the first rib at the costotransverse joint,
      in 12 of the patients. Only three patients did not respond to therapy. Eleven
      patients were engaged in sedentary work. CONCLUSION: Malfunction of the upper
      thoracic aperture, especially among patients doing sedentary work, seems to cause
      TOS symptoms. A carefully planned conservative therapy program based on the
      functional findings of the individual patient is recommended.

PMID- 24572820
TI  - The effect of back injury and load on ability to replicate a novel posture.
AB  - The purpose of this study was to investigate the effect of back injury and load
      on the ability to replicate a target standing posture. Subjects included 16 back
      injured males and 16 age-matched controls. Subjects were asked to reproduce a
      target standing posture and to repeat this task while holding a weight. Trunk
      inclination was measured using an electrogoniometer. Analysis of variance
      indicated that back-injured subjects were less accurate in reproducing the target
      posture than were control subjects. Back-injured subjects typically overestimated
      how much they had moved and therefore underestimated the target position. Both
      groups demonstrated a small but statistically significant difference between the
      load and no-load condition, with greater degrees of trunk inclination under the
      load condition. Analysis of covariance indicated that neither self-reported pain
      level nor maximum voluntary range of motion contributed to significant
      differences between the two groups. These data indicate that, following injury to
      the back, individuals may develop an inaccurate perception of body position. This
      study has implications for training the injured worker. 

PMID- 24572821
TI  - The value of pain drawings in the care of neck and back pain.
AB  - The magnetic resonance imaging (MRI) reports and pain questionnaires of 100
      patients with complaints of lower back or neck pain were reviewed. Prior to
      physician examination, each patient had completed a questionnaire which included
      pain drawings and a rating on a pain scale. The information given on the drawings
      and questionnaires was compared to the MRI reports. The levels of agreement
      between them were analyzed. The results show that the pain questionnaire with
      drawing is a useful tool in the evaluation of patients when the diagnoses of
      herniated nucleus pulposis (HNP) or spinal stenosis are in question. The levels
      of agreement between the pain drawings and the MRI findings were stronger for the
      cervical spine than for the lumbar spine and also stronger for the presence of
      HNP than for central canal spinal stenosis. Particularly useful was the negative
      predictive power for ruling out cervical and lumbar pathology. 

PMID- 24572822
TI  - EMG activity of medial and lateral hamstrings at three positions of tibial
      rotation during low-force isometric knee flexion contractions.
AB  - The purpose of this investigation was to determine how the position of tibial
      rotation effects the EMG activity of the medial and lateral hamstrings during low
      force isometric knee flexion contractions. Forty-five subjects (ages 18-35) with
      no history of lower extremity injury or disease volunteered for this study. While
      lying prone, and with surface EMG electrodes secured to the bellies of their
      right medial (semitendinous and semimembranosus) and lateral (long head of the
      biceps femoris) hamstring muscles, each subject held the knee in 45 degrees  of
      flexion for 8 s against 5% of their body weight. This was performed three times
      in each of the positions of neutral tibial rotation, external tibial rotation,
      and internal tibial rotation. The root-mean-square (RMS) of the EMG activity from
      these muscles was determined for each of the contractions. A repeated measures
      ANOVA was used to compare the RMS values of the two muscle groups in the three
      positions. The average RMS values (in microvolts [mV]) obtained were (means and
      standard deviation): medial hamstrings in external rotation: 50.74 +/- 23.11; in
      neutral: 65.57 +/- 25.35; in internal rotation: 70.73 +/- 31.86; lateral
      hamstrings in external rotation: 66.08 +/- 46.99; in neutral: 46.18 +/- 39.34; in
      internal rotation: 27.68 +/- 17.86. A statistically significant interaction was
      found between tibial rotation and hamstring muscle (p < 0.0001). These results
      are consistent with the presumed function of these muscles in that EMG activity
      in the medial hamstrings increased when the tibia was rotated internally, whereas
      the lateral hamstring EMG activity increased when the tibia was rotated
      externally. 

PMID- 24572823
TI  - Applications of physical and occupational therapy in chronic pain syndrome.
AB  - This article will describe how to approach the prescription of physical therapy
      for 'chronic pain syndrome'. Initial sections will describe script writing for
      physical and occupational therapies, and review types of exercise and physical
      therapeutics. Exercise regimens that the literature supports for patients with
      chronically painful syndromes will also be discussed. The author emphasizes that
      the practitioner cannot write a therapy script for 'chronic pain syndrome.'
      Instead, the practitioner should understand that physical and occupational
      therapy can remedy impairments of flexibility, strength and endurance and the
      patient should be examined to identify these impairments. When the practitioner
      has identified poor flexibility or contracture, weakness or loss of strength, or
      poor endurance in the patient with chronic pain, the practitioner can then write
      a physical therapy or occupational therapy script with goals to improve these
      impairments. It is not necessary for the practitioner to be familiar with the
      nuances of exercise application; it is only necessary for the practitioner to
      identify contracture, weakness and poor endurance, and to direct the therapist's
      attention to these deficits via a therapy script. The practitioner should include
      precautions on a script to a therapist. These precautions are based on the
      patient's concurrent medical and surgical diagnoses. Lastly, the literature
      describing therapeutic interventions in patients with chronic pain syndromes is
      poor because the painful conditions are poorly characterized and the therapeutic
      interventions are poorly described; however, where specific exercise programs for
      specific diagnoses were identified, the exercise regimens are discussed. 

PMID- 24572824
TI  - Hope: critical therapy.
AB  - According to a recent Time magazine article, a 1995 study at Dartmouth-Hitchcock
      Medical Center found that one of the best predictors of survival among 232 heart
      surgery patients was the degree to which the patients said they drew comfort and
      strength from religious faith. Those who did not had more than three times the
      death rate of those who did (June 24, 1996, pp. 59-68) Likewise, according to the
      article, numerous studies have found lower rates of depression among the
      religiously committed.The article goes on to state that patients with chronic
      health problems are failing to find relief in a doctor's office, and the
      increasing use of high-tech scans and tests of modern medicine leave patients
      feeling uncared for and alienated.Dr. Herbert Benson, President of the Mind/Body
      Medical Institute at Boston's Deaconess Hospital and Harvard Medical School, in
      his book, Timeless Healing, demonstrated the role of meditation and spirituality
      in patients battling chronic illnesses. A 5-year study found that those who
      claimed to feel the intimate presence of a higher power had better health and
      more rapid recoveries.As clinicians, we were not trained to recognize or teach
      our patients how to act on the role of faith and hope in healing. However, as
      researchers, we cannot dismiss the possibility that there is a definite
      relationship.The following commentary is offered to you as food for thought.
      Today, as we continue to seek ways to reduce health care costs while still
      providing effective methods of treating illness, we must not rule out factors
      such as faith and hope in meeting our ultimate goal of healing the sick. 

PMID- 24572825
TI  - Letters to the editor.

PMID- 24572826
TI  - Control of non-pain symptoms in HIV/AIDS.

PMID- 24572827
TI  - Erratum to "Theory and practice of myofascial pain as both practicing clinician
      and patient" (a Physician Commentary)[J. Back Musculoskeletal Rehabil. 8 (1997)
      173].

PMID- 24572828
TI  - The European spine society: the acromed prize for spinal research 1997.

PMID- 24572830
TI  - Author IndexVolume 8 (1997).

PMID- 24572832
TI  - Volume contentsVolume 8 (1997).

PMID- 24572833
TI  - Acylated and unacylated ghrelin administration to blunt muscle wasting.
AB  - PURPOSE OF REVIEW: Muscle wasting is a comorbidity often associated with a wide
      range of disorders that severely affects patient prognosis and quality of life.
      Ghrelin, through its receptor GHSR-1a, stimulates appetite and growth hormone
      (GH) release. Several studies indicate that ghrelin administration is a valid
      treatment for cachexia because it improves muscle mass and function, likely by
      restoring a positive energy balance. RECENT FINDINGS: In addition to its GHSR-1a
      mediated effects on muscle mass, ghrelin acts directly on skeletal muscle,
      wherein it exerts a protective activity against muscle wasting. This direct
      activity is independent of GHSR-1a and is shared by the unacylated form of
      ghrelin, which does not bind GHSR-1a and is devoid of the effects on appetite and
      GH release. SUMMARY: Both the acylated and unacylated forms of ghrelin might have
      therapeutic potential for the treatment of skeletal muscle wasting.

PMID- 24572834
TI  - Do patients with advanced cancer have any potential for protein anabolism in
      response to amino acid therapy?
AB  - PURPOSE OF REVIEW: There is evidence that protein anabolism is achievable before
      cancer evolves into refractory cachexia with attenuation of muscle loss and even
      muscle gain. This review summarizes recent observations on the role of total and
      specific amino acids in promoting protein anabolism in human cancer and revisits
      prior studies in this context. RECENT FINDINGS: Analysis of muscle changes in
      advanced cancer patients indicated opportunities for inducing anabolism.
      Maintenance and gain in muscle was reported in a majority of patients, from
      initiation of oncologic treatment and before the final refractory stage. In
      addition to being substrates, some amino acids, for example leucine, act as
      intracellular signals to promote protein synthesis. Recent acute studies
      demonstrated that provision of amino acids, sufficient to considerably elevate
      circulating leucine concentrations concurrent with other amino acid and nutrient
      availability, resulted in significant protein anabolism in cancer patients. This
      occurred even during weight loss and inflammation. SUMMARY: Patients with cancer
      have an anabolic potential to be exploited early on in cachexia development. High
      leucine and protein supplements are worth testing as part of a multimodal
      anabolic approach in long-term trials to confirm their efficacy to sustain
      anabolism, and attenuate or even reverse muscle wasting.

PMID- 24572835
TI  - Multimodal nutrition/anabolic therapy for wasting conditions.
AB  - PURPOSE OF REVIEW: Significant progress has been made in the field of defining
      and describing the pathophysiology of wasting conditions such as cachexia. The
      number of new promising drugs, nutritional therapy alternatives, and
      exercise/rehabilitation programs is increasing. The purpose of this review is to
      give an overview of recent clinical findings from intervention studies
      investigating multimodal anabolic therapies utilizing drug, nutritional, and/or
      exercise interventions in order to counteract wasting. RECENT FINDINGS: Anabolic
      agents such as ghrelin and selective androgen receptor modulators are under late
      phase clinical testing and hold promise as new therapies, and their ability to
      mitigate weight loss and improve muscle mass and physical function is evaluated.
      In the past 2 years, eight new studies investigating interventions with anabolic
      potential in wasting have been published, among which three of these studies were
      multimodal. SUMMARY: Targeted anabolic therapies aiming to prevent or reverse
      wasting might involve a combination of anabolic pharmacologic drugs, nutrition,
      and physical exercise working concurrently to enhance muscle protein synthesis
      and reduce breakdown. Some anabolic pharmacological interventions demonstrate the
      potential to improve muscle mass, but the multimodal interventions seem in
      greater extent to also demonstrate improvement in physical function.

PMID- 24572836
TI  - Prenatal and postnatal nutrition for future health.

PMID- 24572837
TI  - Mixtures with relatives: a pedigree perspective.
AB  - DNA mixture evidence pertains to cases where several individuals may have
      contributed to a biological stain. Statistical methods and software for such
      problems are available and a large number of cases can be handled adequately.
      However, one class of mixture problems remains untreated in full generality in
      the literature, namely when the contributors may be related. Disregarding a
      plausible close relative of the perpetrator as an alternative contributor
      (identical twin is the most extreme case) may lead to overestimating the evidence
      against a suspect. Existing methods only accommodate pairwise relationships such
      as the case where the suspect and the victim are siblings, for example. In this
      paper we consider relationships in full generality, conveniently represented by
      pedigrees. In particular, these pedigrees may involve inbreeding, for instance
      when the parents of an individual of interest are first cousins. Furthermore our
      framework handles situations where the opposing parties in a court case
      (prosecution and defence) propose different family relationships. Consequently,
      our approach combines classical mixture and kinship problems. The basic idea of
      this paper is to formulate the problem in a way that allows for the exploitation
      of currently available methods and software designed originally for linkage
      applications. We have developed a freely available R package, euroMix based on
      another package, paramlink, and we illustrate the ideas and methods on real and
      simulated data. 

PMID- 24572838
TI  - The multiple core-shell structure in Cu(24)Ln(6) cluster with magnetocaloric
      effect and slow magnetization relaxation.
AB  - Triple core-shell structures in the Cu24Gd6 and Cu24Dy6 clusters were first
      observed and structurally characterized. The magnetic investigations reveal that
      Cu24Gd6 possesses the significant magnetic entropy change (-DeltaSm) of 21.2 J
      kg(-1) K(-1) for DeltaH = 7 T, and a slow magnetization relaxation is observed in
      Cu24Dy6. 

PMID- 24572839
TI  - Economic implications of recent trends in U.S. immediate autologous breast
      reconstruction.
AB  - BACKGROUND: Recent trends in U.S. breast oncology and autologous reconstruction,
      such as greater use of contralateral prophylactic mastectomies and microsurgery,
      may have increased reconstructive complication rates and costs. Simultaneously,
      with the increased complexity of autologous reconstruction in the setting of
      declining reimbursement, there may be market concentration of these procedures to
      specialized high-volume centers. This study aimed to (1) measure cost of
      autologous reconstruction in the setting of microsurgical technique,
      contralateral prophylactic mastectomies, and high-volume centers; and (2) analyze
      trends in market share of these procedures. METHODS: Inflation-adjusted hospital
      charges were analyzed for autologous procedures using the Nationwide Inpatient
      Sample database (1998 to 2010), including a subgroup of microsurgical cases.
      Median charges were adjusted by patient case mix and analyzed by outcome,
      procedure type, and hospital volume using the Mann-Whitney test. Market share was
      evaluated through examination of trends in hospitals performing autologous
      reconstruction and procedures at high-volume centers. RESULTS: Median charges for
      21,016 autologous reconstructions were $22,198. Costs were higher for bilateral
      reconstruction ($34,202) and microsurgical cases ($57,449). Hospital charges
      increased from $20,315 (no complications) to $42,210 when both surgery-specific
      and systemic complications were present (p < 0.01). High-volume hospitals reduced
      charges by 7.5 percent and had lower costs in the setting of complications (p <
      0.01). The number of hospitals performing autologous reconstructions decreased 35
      percent, with increasing annual procedures in high-volume centers (48.3 to 73.3,
      p < 0.01). CONCLUSIONS: Bilateral reconstructions and microsurgical technique are
      associated with greater health care costs. The market concentration of autologous
      reconstruction to high-volume centers is associated with reduced charges. The
      long-term implications of this trend are unknown.

PMID- 24572840
TI  - Comparative analysis of 18-month outcomes and costs of breast reconstruction flap
      procedures.
AB  - BACKGROUND: Data from large-scale studies of breast reconstruction surgery
      outcomes and downstream costs are lacking. The authors assessed outcomes, patient
      return rates, and costs across a large, geographically diverse patient population
      undergoing autologous breast reconstruction. METHODS: Insurance claims for
      patients undergoing free flap, latissimus dorsi flap, or transverse rectus
      abdominis myocutaneous (TRAM) flap autologous breast reconstruction were
      extracted from a U.S. health care database. Claims for an 18-month period after
      the initial (index) procedure were analyzed to assess episodes of care,
      complications, breast procedures, and costs. RESULTS: Of 828 patients (274 free
      flaps, 302 latissimus dorsi flaps, and 252 TRAM flaps), 35 percent experienced
      postindex complications: incidences related to implant/graft/mesh and
      hematoma/seroma were highest in the latissimus dorsi arm (19 percent and 6
      percent, respectively); the incidence related to breast necrosis was highest in
      the free flap arm (8 percent); and that related to wound complications was
      highest in the TRAM arm (6 percent). Returns for complications were 92.7, 84.4,
      and 115.5 of 100 patients in the free, latissimus dorsi, and TRAM flap arms (p <
      0.05, TRAM flap versus other arms), respectively, and 105.5, 116.6, and 87.7 of
      100 patients, respectively, for procedures unrelated to complications (p < 0.05,
      latissimus dorsi versus TRAM flaps). Nearly all patients returned at least once
      for treatments unrelated to complications. Mean total costs for index surgery
      plus postindex events were $56,205, $30,783, and $33,380 in the free, latissimus
      dorsi, and TRAM flap arms, respectively. CONCLUSIONS: Eighteen-month complication
      and return rates for postindex events were similar across study arms. The
      frequency of returns and associated cost of procedures unrelated to complications
      point to the inherently staged nature of autologous breast reconstruction.
      CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

PMID- 24572841
TI  - Discussion: Comparative analysis of 18-month outcomes and costs of breast
      reconstruction flap procedures.

PMID- 24572842
TI  - Abdominally based free flap planning in breast reconstruction with computed
      tomographic angiography: systematic review and meta-analysis.
AB  - BACKGROUND: Computed tomographic angiography is often used for preoperative
      mapping. The authors aimed to systematically assess breast reconstruction
      outcomes after abdominally based free flaps planned with preoperative computed
      tomographic angiography versus Doppler ultrasonography. METHODS: A search of the
      PubMed, EMBASE, and Scopus databases and an additional hand-search of relevant
      articles until June of 2012 rendered 442 English-language citations. Three
      authors independently reviewed these citations and included all the studies
      comparing preoperative computed tomographic angiography versus Doppler
      ultrasonography with regard to short-term postoperative outcomes and operative
      times. A meta-analysis was performed to evaluate the incidence of flap-related
      complications (seven studies), donor-site morbidity (four studies), and operative
      times (five studies) between preoperative computed tomographic angiography and
      Doppler ultrasonography. A pooled relative risk was calculated using a random
      effect model to compare complication rates between the computed tomographic
      angiography and Doppler ultrasonography groups. RESULTS: A total of 13 studies
      met inclusion criteria. Preoperative computed tomographic angiography was
      associated with significantly fewer flap-related complications (relative risk,
      0.87; 95 percent CI, 0.78 to 0.97), reduced donor-site morbidity (relative risk,
      0.84; 95 percent CI, 0.76 to 0.94), and shorter reconstruction operative time by
      87.7 minutes (mean difference, 87.7 minutes; 95 percent CI, 78.3 to 97.1
      minutes). CONCLUSIONS: The use of preoperative computed tomographic angiography
      reduces the operative time, postoperative flap-related complications, and donor
      site morbidity compared with Doppler ultrasonography. Preoperative computed
      tomographic angiography has the potential to reduce operative cost and increase
      efficiency in the operating room. Thus, preoperative mapping by computed
      tomographic angiography should be strongly considered for abdominally based free
      flap breast reconstruction.

PMID- 24572843
TI  - Breast reconstruction following nipple-sparing mastectomy: predictors of
      complications, reconstruction outcomes, and 5-year trends.
AB  - BACKGROUND: Nipple-sparing mastectomy is increasingly used for treatment and
      prevention of breast cancer. Few data exist on risk factors for complications and
      reconstruction outcomes. METHODS: A single-institution retrospective review was
      performed between 2007 and 2012. RESULTS: Two hundred eighty-five patients
      underwent 500 nipple-sparing mastectomy procedures for breast cancer (46 percent)
      or risk reduction (54 percent). The average body mass index was 24, and 6 percent
      were smokers. The mean follow-up was 2.17 years. Immediate breast reconstruction
      (reconstruction rate, 98.8 percent) was performed with direct-to-implant (59
      percent), tissue expander/implant (38 percent), or autologous (2 percent)
      reconstruction. Acellular dermal matrix was used in 71 percent and mesh was used
      in 11 percent. Seventy-seven reconstructions had radiotherapy. Complications
      included infection (3.3 percent), skin necrosis (5.2 percent), nipple necrosis
      (4.4 percent), seroma (1.7 percent), hematoma (1.7 percent), and implant loss
      (1.9 percent). Positive predictors for total complications included smoking (OR,
      3.3; 95 percent CI, 1.289 to 8.486) and periareolar incisions (OR, 3.63; 95
      percent CI, 1.850 to 7.107). Increasing body mass index predicted skin necrosis
      (OR, 1.154; 95 percent CI, 1.036 to 1.286) and preoperative irradiation predicted
      nipple necrosis (OR, 4.86; 95 percent CI, 1.0197 to 23.169). An inframammary fold
      incision decreased complications (OR, 0.018; 95 percent CI, 0.0026 to 0.12089).
      Five-year trends showed increasing numbers of nipple-sparing mastectomy with
      immediate reconstruction and more single-stage versus two-stage reconstructions
      (p < 0.05). CONCLUSIONS: Nipple-sparing mastectomy reconstructions have a low
      number of complications. Smoking, body mass index, preoperative irradiation, and
      incision type were predictors of complications. CLINICAL QUESTION/LEVEL OF
      EVIDENCE: Risk, III.

PMID- 24572844
TI  - The deviated nose and asymmetric eyebrows: an important trap to avoid.
AB  - BACKGROUND: Failure to recognize asymmetrically positioned eyebrows, often
      altered by the patient to camouflage nasal asymmetry, can lead the surgeon to
      design the rhinoplasty using a faulty midline landmark. The purpose of this study
      was to investigate the frequency of eyebrow asymmetry and to test whether there
      is an association between eyebrow position and the direction of nasal deviation.
      METHODS: Life-size photographs of 100 rhinoplasty patients were selected randomly
      from the senior author's (B.G.) practice. Nasal deviation from the midpoint of
      the intercanthal distance was measured at standardized levels on anteroposterior
      views corresponding to the nasal bones, upper lateral cartilages, and nasal tip.
      The maximally deviated parameter was noted. RESULTS: Of the 27 men and 73 women
      studied, 96 patients had measurable eyebrow asymmetry, including 96 percent of
      men and 96 percent of women. All 100 patients had at least one level of nasal
      deviation. The direction of eyebrow shift correlated significantly with the
      direction of nasal deviation for nasal bones (p = 0.0018), nasal tip (p =
      0.0032), and maximally deviated parameter (p = 0.039), but not for upper lateral
      cartilages (p = 0.54). Mean eyebrow shift distance for male patients (1.8 mm) and
      female patients (1.3 mm) was not significantly different (p = 0.056).
      CONCLUSIONS: The frequency of eyebrow asymmetry and the significant correlation
      between eyebrow position and nasal deviation direction suggest that eyebrows can
      camouflage nasal deformities. Furthermore, the alarmingly high incidence of nasal
      deviation in rhinoplasty candidates emphasizes the value of a circumspect
      preoperative nasal analysis in reducing the incidence of residual postoperative
      nose deviation. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, IV.

PMID- 24572845
TI  - Discussion: The deviated nose and asymmetric eyebrows: an important trap to
      avoid.

PMID- 24572846
TI  - A process for quantifying aesthetic and functional breast surgery: II. Applying
      quantified dimensions of the skin envelope to design and preoperative planning
      for mastopexy and breast reduction.
AB  - BACKGROUND: A previous submission defined methods to objectively define nipple
      position and vertical and horizontal skin excess in mastopexy and breast
      reduction. This article defines a set of second-stage processes for quantified
      design and operative planning for skin envelope modification. METHODS: A skin
      envelope modification procedure (periareolar, periareolar plus vertical, or
      periareolar plus vertical plus horizontal) was selected based on the quantified
      amount of vertical skin excess. This process was applied in 124 consecutive
      mastopexy and 122 consecutive breast reduction cases. Average follow-up was 4.6
      years (range, 6 to 14 years). RESULTS: All cases were assessed, planned, and
      executed applying the processes in this article. No patient required nipple
      repositioning. Complications included excessive lower pole restretch (4 percent),
      periareolar scar hypertrophy (0.8 percent), hematoma (1.2 percent), and areolar
      shape irregularities (1.6 percent). Delayed healing at the junction of vertical
      and horizontal scars occurred in two reduction patients [two of 124 (1.6
      percent)], neither of which required revision. The overall reoperation rate was
      6.5 percent (16 of 246) for patients in the first 5 years of the study and
      decreased to 1.6 percent for patients from year 6 through year 14. CONCLUSIONS:
      This study defines processes for using objectively defined parameters for skin
      envelope modification in mastopexy and breast reduction. Quantifying desired skin
      envelope design enables surgeons to objectively quantify vertical skin excess and
      horizontal skin excess, select envelope modification design and techniques based
      on those parameters, and evaluate outcomes based on objective clinical
      measurements in both mastopexy and breast reduction. CLINICAL QUESTION/LEVEL OF
      EVIDENCE: Therapeutic, IV.

PMID- 24572847
TI  - Is the high superior tension technique an equivalent substitute for progressive
      tension sutures in postbariatric abdominoplasty? A comparison prospective study.
AB  - BACKGROUND: The addition of progressive tension sutures to the abdominoplasty
      technique is advocated to reduce the risk of several complications. High superior
      tension abdominoplasty is another technique aimed at reducing tension at the
      prepubic suture line and improving cosmesis of the umbilical area. METHODS: A
      cohort of massive weight loss patients undergoing abdominoplasty, treated with
      the progressive tension suture technique in association with the high superior
      tension technique (group A), was followed up and compared to a cohort of patients
      who underwent high superior tension abdominoplasty (group B). Several variables
      including rate of complications and patient satisfaction were explored to
      determine any possible benefit deriving from the combination of progressive
      tension suture and high superior tension techniques in the abdominoplasty.
      RESULTS: A total of 90 patients were included in the study, of whom 34 were in
      group A and 56 were in group B. No statistically significant difference was found
      between the two groups in terms of duration of the procedure, hospitalization
      time, rate of complications, drained volume, and patient or physician
      satisfaction. CONCLUSION: No beneficial effect appears to derive from the
      progressive tension suture technique in massive weight loss patients undergoing
      abdominoplasty, provided that the high superior tension technique is performed as
      an adjunct to the traditional method.

PMID- 24572848
TI  - Megavolume autologous fat transfer: part I. Theory and principles.
AB  - This article describes the theory and principles behind the authors' success in
      megavolume (250-ml range) autologous fat transfer to the breasts. When large
      volumes are grafted into a tight space, the interstitial fluid pressure increases
      to impair capillary blood flow and the crowded graft droplets coalesce into
      lakes, with poor graft-to-recipient interface. These factors have historically
      restricted the volume of fat that can be grafted into small recipient breasts.
      The decreased interface increases the distance oxygen must diffuse to reach the
      grafted adipocytes, causing central necrosis to occur before neovascularization.
      The increased interstitial fluid pressure reduces capillary radius, reducing
      oxygen delivery to grafted adipose tissue. The Brava external expansion device
      harnesses the regenerative capabilities of mechanical forces to preoperatively
      increase the volume and vascularity of the recipient site, allowing megavolumes
      of fat to be grafted diffusely without significantly decreasing graft-to
      recipient interface or increasing interstitial fluid pressure. The application of
      these principles has allowed the authors to successfully graft megavolumes of fat
      into the breasts of over 1000 patients with substantial long-term retention.

PMID- 24572849
TI  - Discussion: Megavolume autologous fat transfer: part I. Theory and principles.

PMID- 24572850
TI  - The graft-to-capacity ratio: volumetric planning in large-volume fat
      transplantation.
AB  - BACKGROUND: Variability in large-volume fat transplantation has been linked to
      technique. Meanwhile, the recipient-site volume and its relation to the volume of
      grafted fat have been relatively overlooked. Graft-to-capacity concepts are
      evidenced in other soft-tissue transplantation procedures such as skin and hair
      transplantation. The authors define the graft-to-capacity ratio as the volume of
      grafted fat in relation to the volume of the recipient site. The authors
      postulate its theoretical limits, and empirically analyze its potential clinical
      importance in large-volume fat transplantation. METHODS: Thirty cases of large
      volume fat transplantation to the breast were reviewed. All patients underwent
      (1) preoperative quantitative volumetric analysis using three-dimensional breast
      imaging and (2) large-volume fat transplantation using the large-syringe
      technique. The volume of fat transplanted into each breast at the time of surgery
      was noted. Quantitative volumetric breast imaging was repeated 12 months
      postoperatively. RESULTS: The average graft-to-capacity ratio was 117 percent,
      with a standard deviation of 22 percent, consistent with deduced theoretical
      limits. Cases where the graft-to-capacity ratio exceeded 1 SD demonstrated lower
      percentage volume maintenance. Cases where the graft-to-capacity ratio was lower
      than 1 SD appeared to demonstrate higher percentage volume maintenance.
      Univariate linear regression of percentage volume maintenance as a function of
      the graft-to-capacity ratio demonstrated a significant inverse relationship.
      CONCLUSION: The graft-to-capacity ratio appears to be a relevant variable in
      percentage volume maintenance outcomes and may be useful in establishing
      consistency in large-volume fat transplantation. CLINICAL QUESTION/LEVEL OF
      EVIDENCE: Therapeutic, IV.

PMID- 24572851
TI  - Transplantation of the LGR6+ epithelial stem cell into full-thickness cutaneous
      wounds results in enhanced healing, nascent hair follicle development, and
      augmentation of angiogenic analytes.
AB  - BACKGROUND: The recently discovered leucine-rich repeat-containing G-protein
      coupled receptor 6 (LGR6+) epithelial stem cell located within the follicular
      bulge of the adnexal compartment is capable of producing all cellular lineages of
      the skin. In this study, the authors sought to determine whether these cells can
      be transplanted for use as a type of cellular therapy for the repair of full
      thickness wounds in which the native stem cell niche has been obliterated.
      METHODS: Full-thickness murine skin was harvested and LGR6(+GFP) epithelial stem
      cells were isolated using fluorescence-activated cell sorting. This enriched
      epithelial stem cell population was then transplanted by means of local injection
      into wound beds on the dorsum of nude mice. Viability, migration, healing, the
      development of nascent hair follicles, and gene and proteomic expression studies
      were performed to determine whether the engraftment of LGR6(+GFP) epithelial stem
      cells enhanced healing when compared with controls. RESULTS: Wound beds receiving
      LGR6(+GFP) epithelial stem cells showed enhanced healing; nascent follicle
      growth; and augmentation of the Wnt, vascular endothelial growth factor,
      epidermal growth factor, and platelet-derived growth factor pathways when
      compared with controls. CONCLUSIONS: The LGR6+ epithelial stem cells appear to
      hold great promise for the development of a clinically useful stem cell-based
      therapy for the repair of full-thickness wounds and hair regeneration. These
      results indicate that transplantation of LGR6+ epithelial stem cells promotes
      epithelialization, hair growth, and angiogenesis in tissues destined for scar
      formation.

PMID- 24572852
TI  - Osteoarthritis of the wrist.
AB  - This article reviews pathogenesis and treatment of wrist osteoarthritis. Because
      there is no cure for osteoarthritis, treatment is directed at symptomatic relief.
      Surgical treatment is reserved for patients who have failed nonoperative
      modalities. This article reviews the surgical treatment of wrist osteoarthritis
      with an emphasis on selection of the appropriate procedure. Literature guiding
      surgical treatment with patient outcomes is reviewed.

PMID- 24572853
TI  - Determining the Michigan Hand Outcomes Questionnaire minimal clinically important
      difference by means of three methods.
AB  - BACKGROUND: To interpret patient-rated outcome measures, clinicians rely on the
      minimal clinically important difference. The authors studied the range of minimal
      clinically important difference scores for the overall Michigan Hand Outcomes
      Questionnaire score its and subscales in a population with various diagnoses and
      treatments. METHODS: Patients with a single, unilateral, atraumatic hand/forearm
      diagnosis completed the Michigan Hand Outcomes Questionnaire before treatment and
      at 4 +/- 1 weeks and 12 +/- 2 weeks after treatment. Three methods were used to
      calculate the minimal clinically important difference: two anchor question
      methods based on satisfaction (mean change and receiver operating characteristic)
      and a statistical distribution method. RESULTS: One hundred eighty-six patients
      were enrolled, with a baseline median overall questionnaire score of 60.7. Using
      the mean change method, a minimal clinically important difference of 13 was
      calculated for the overall questionnaire score. Using a receiver operating
      characteristic curve (0.8 effect size), the minimal clinically important
      difference was 9, with an area under the curve of 0.92. When receiver operating
      characteristic analysis was based on dichotomization of reported satisfaction,
      the minimal clinically important difference was 12, with an area under the curve
      of 0.85. Calculating the difference by statistical distribution gave a value of
      8. For the subscales, by all methods, triangulated minimal clinically important
      difference estimates ranged from 10.9 to 14.4. CONCLUSIONS: The minimal
      clinically important difference for the overall Michigan Hand Outcomes
      Questionnaire score in atraumatic hand/forearm conditions falls between 8 and 13.
      Multiple analytic methods produce nonidentical but similar minimal clinically
      important differences. The authors recommend using difference estimates in these
      ranges when planning a clinical trial to investigate hand/forearm function across
      a range of diagnoses and treatments.

PMID- 24572854
TI  - Three-dimensional computed tomography reveals different donor-site deformities in
      adult and growing microtia patients despite total subperichondrial costal
      cartilage harvest and donor-site reconstruction.
AB  - BACKGROUND: Donor-site deformity may complicate autologous costal cartilage
      harvest for microtia reconstruction. This is reportedly prevented by total
      subperichondrial costal cartilage harvest, costochondral growth center
      preservation, donor-site reconstitution with morselized leftover costal
      cartilage, and perichondrial repair (Kawanabe-Nagata method). However, no
      quantitative assessment of preoperative versus postoperative thoracic morphology
      exists following use of this method. METHODS: Twenty-five consecutive patients
      (11 adult and 14 growing patients) who received radiographic donor-site
      evaluation for autologous unilateral primary microtia reconstruction were
      studied. Each underwent thoracic three-dimensional computed tomography
      preoperatively and 6 months postoperatively. The authors quantified (1) donor
      site skeletal deformation with respect to the sixth to ninth costochondral
      junctions (2) and distortion in thoracic/hemithoracic Haller indices. The
      contralateral unoperated hemithorax provided intrapatient control data. RESULTS:
      Statistically significant deformations occurred in the sagittal and transverse
      planes in growing patients and in the transverse plane in adults, with respect to
      most costochondral junctions on operated versus unoperated sides. Importantly, in
      growing patients, the sixth to ninth costochondral junctions on the operated side
      failed to descend postoperatively with normal growth in the vertical plane,
      unlike on the unoperated side. However, no gross distortions in
      thoracic/hemithoracic proportions occurred according to Haller indices.
      CONCLUSIONS: Despite meticulous donor-site management and reconstruction
      according to the Kawanabe-Nagata method, patients sustained significant localized
      skeletal deformations, as quantified by three-dimensional computed tomography,
      the configurations of which differed according to whether patients were adult or
      growing when operated on. Whether these improve or worsen in the long term,
      particularly in growing patients, requires confirmation. CLINICAL QUESTION/LEVEL
      OF EVIDENCE: Therapeutic, III.

PMID- 24572855
TI  - Single-stage autologous ear reconstruction for microtia.
AB  - BACKGROUND: The authors have been using the Nagata technique since 2002. In this
      review of 100 consecutive ear reconstructions, the authors present technique
      modifications that have evolved over this period that have contributed to
      improved auricular contour and that now allow for auricular reconstruction in a
      single stage. METHODS: This study is a retrospective review of a prospectively
      acquired database. The series is restricted to primary reconstructions performed
      for congenital microtia. Photographs of 10 consecutive patients are presented to
      demonstrate the results of the technique. Surgical complication rates are
      discussed. RESULTS: One hundred ear reconstructions were performed in 96
      patients. There were 75 primary cases of congenital microtia. Twenty-four ears
      underwent a two-stage reconstruction, and 51 ears were reconstructed with a
      Nagata stage I procedure or a single-stage reconstruction. There was a gradual
      shift in technique, with a trend to perform fewer Nagata stage II outsetting
      procedures and more single-stage reconstructions. In patients who underwent an
      ear reconstruction in two stages, the surgical complication rate was 22 percent.
      In the last 40 consecutive ear reconstructions since abandoning the two-stage
      approach, the surgical complication rate is now 15 percent. CONCLUSIONS: A
      modification of Nagata's technique of autologous ear reconstruction for microtia
      is described. Modifications of the three-dimensional framework address the
      contour of the inferior crus and control tragal projection and position.
      Inclusion of a projection block and recruitment of retroauricular skin allow for
      symmetric projection of the ear in a single stage. CLINICAL QUESTION/LEVEL OF
      EVIDENCE: Therapeutic, IV.

PMID- 24572856
TI  - Discussion: Single-stage autologous ear reconstruction for microtia.

PMID- 24572858
TI  - The submental island flap for soft-tissue head and neck reconstruction: step-by
      step video description and long-term results.
AB  - A clinical case of a man undergoing radical parotidectomy with skin resection for
      an intraparotid recurrence of squamous cell carcinoma is presented. A step-by
      step video description of the regional submental island flap, based on the right
      submental vessels, is presented and discussed. Long-term results at 1 year in
      terms of color match at the recipient and donor sites are excellent, along with
      no functional consequence. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.

PMID- 24572857
TI  - Deferoxamine enhances bone regeneration in mandibular distraction osteogenesis.
AB  - BACKGROUND: Distraction osteogenesis is a powerful reconstructive technique for
      bone growth and repair. An angiogenic means of enhancing the efficacy of this
      metabolically demanding procedure would be beneficial in expanding its
      therapeutic potential. The authors posit that the angiogenic effect of
      deferoxamine, an iron chelator that has been shown to increase angiogenesis, will
      improve bone regeneration by means of augmentations in quality and quantity of
      bone and bone-producing cells. METHODS: Two groups of rats (n = 12) underwent
      surgical external fixation and subsequent distraction. During the distraction
      stage, the experimental deferoxamine group (n = 5) was treated with injections
      into the distraction gap. After 28 days of consolidation, mandibles were
      harvested and prepared for histologic analysis. RESULTS: The authors found a
      proliferation of osteocytes in the deferoxamine-treated group when compared with
      the regenerate of the control group. Deferoxamine effected a significant increase
      in osteocytes and an increase in bone volume fraction, with subsequent decreased
      osteoid volume fraction. The data also demonstrated no significant difference in
      empty lacunae. CONCLUSIONS: The authors' study demonstrates the effectiveness of
      deferoxamine treatment to enhance the number of osteocytes within the regenerate
      in a murine mandibular distraction osteogenesis model. Maintenance of full
      lacunae supports the authors' finding of a robust cellular response to
      deferoxamine therapy. These results suggest that the angiogenic capabilities of
      deferoxamine translate into an increase in the number of bone-forming cells in
      the regenerate. Deferoxamine may have utility in optimizing bone formation in
      distraction osteogenesis and lead to superior reconstructive capabilities for
      craniofacial surgeons in the future.

PMID- 24572859
TI  - Reinforcement of the abdominal wall following breast reconstruction with
      abdominal flaps: a comparison of synthetic and biological mesh.
AB  - BACKGROUND: Breast reconstruction using muscle-preserving abdominal flaps
      occasionally results in an abdominal bulge or hernia. The authors analyzed
      outcomes and complications following use of a synthetic or biological mesh for
      abdominal reinforcement following initial harvest or secondary repair of a bulge
      or hernia. METHODS: A retrospective review was conducted of all patients (n =
      818) who had abdominal flap-based breast reconstruction between 1995 and 2011.
      Ninety-seven patients met inclusion criteria; 61 had synthetic mesh and 36 had
      biological mesh (porcine acellular dermal matrix). Complications and outcomes
      were reviewed. Statistical analysis was performed to determine contributing
      factors and differences between cohorts. RESULTS: Overall complication rates for
      the synthetic and biological cohorts were 6.5 and 5.5 percent (p = 0.61),
      respectively, with slightly higher bulge rates in patients with synthetic
      compared with biological mesh (18 percent versus 8.3 percent; p = 0.25).
      Complication rates in primary and secondary placement of synthetic mesh were 5
      and 7.3 percent, respectively; bulge rates were 15 and 19.5 percent,
      respectively. Complication rates in primary and secondary placement of biological
      mesh were 6.3 and 0 percent, respectively; bulge rates were 9.4 and 0 percent,
      respectively. CONCLUSIONS: Synthetic and biological mesh reconstruction for
      primary abdominal repair and secondary contouring have similar, low complication
      rates. Postoperative abdominal wall laxity and bulge occurred in an equal
      distribution following unilateral or bilateral flap reconstruction. Early
      investigation demonstrates that porcine acellular dermal matrix is as effective
      as synthetic mesh for abdominal wall reinforcement and repair, with limited
      morbidity associated with each. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic,
      III.

PMID- 24572860
TI  - The impact of negative-pressure wound therapy with instillation compared with
      standard negative-pressure wound therapy: a retrospective, historical, cohort,
      controlled study.
AB  - BACKGROUND: Negative-pressure wound therapy with instillation is a novel wound
      therapy that combines negative pressure with instillation of a topical solution.
      METHODS: This retrospective, historical, cohort-control study examined the impact
      of negative-pressure wound therapy with and without instillation. RESULTS: One
      hundred forty-two patients (negative-pressure wound therapy, n = 74; therapy with
      instillation, 6-minute dwell time, n = 34; and therapy with instillation, 20
      minute dwell time, n = 34) were included in the analysis. Number of operative
      visits was significantly lower for the 6- and 20-minute dwell time groups (2.4 +/
      0.9 and 2.6 +/- 0.9, respectively) compared with the no-instillation group (3.0
      +/- 0.9) (p <= 0.05). Hospital stay was significantly shorter for the 20-minute
      dwell time group (11.4 +/- 5.1 days) compared with the no-instillation group
      (14.92 +/- 9.23 days) (p <= 0.05). Time to final surgical procedure was
      significantly shorter for the 6- and 20-minute dwell time groups (7.8 +/- 5.2 and
      7.5 +/- 3.1 days, respectively) compared with the no-instillation group (9.23 +/-
      5.2 days) (p <= 0.05). Percentage of wounds closed before discharge and culture
      improvement for Gram-positive bacteria was significantly higher for the 6-minute
      dwell time group (94 and 90 percent, respectively) compared with the no
      instillation group (62 and 63 percent, respectively) (p <= 0.05). CONCLUSION: The
      authors' results suggest that negative-pressure wound therapy with instillation
      (6- or 20-minute dwell time) is more beneficial than standard negative-pressure
      wound therapy for the adjunctive treatment of acutely and chronically infected
      wounds that require hospital admission. CLINICAL QUESTION/LEVEL OF EVIDENCE:
      Therapeutic, III.

PMID- 24572861
TI  - Intercostal neuroma pain after laparoscopic cholecystectomy: diagnosis and
      treatment.
AB  - BACKGROUND: Chest wall or abdominal pain after laparoscopic cholecystectomy is
      perceived as residual gastrointestinal problems. Some patients will have
      tenderness at the laparoscopic portal site(s), representing injury to one or more
      intercostal nerves. The author describes this patient population for the first
      time, outlining a diagnostic and therapeutic algorithm. METHODS: Inclusion
      criteria included (1) right chest wall or abdominal pain persisting more than 1
      year after laparoscopic cholecystectomy, (2) relief of that pain with intercostal
      nerve block, (3) resection of intercostal nerves identified by nerve block, and
      (4) at least a 6-month postoperative follow-up by telephone. Review from 2009
      through 2011 identified one man and seven women meeting these criteria. Mean age
      was 44 years (range, 18 to 74 years). Mean interval between cholecystectomy and
      intercostal neurectomy was 44.3 months (range, 13 to 72 months). RESULTS: Two
      intercostal nerves were resected in two patients, three in four patients, four in
      one patient, and five in one patient, most commonly intercostal nerves T6, T7,
      and T8. Proximal nerves were implanted into the serratus or latissimus dorsi. At
      a mean period of 18.3 months after surgery, the preoperative mean visual analogue
      score of 8.9 (range, 7 to 10) decreased to 3.6 (range, 0 to 6) (p < 0.01).
      Overall results were excellent in five (63 percent) and good in two (25 percent),
      with one failure (12 percent). CONCLUSIONS: Pain following laparoscopic
      cholecystectomy may represent intercostal nerve injury. Diagnostic blocks are
      essential to confirm diagnosis. Nerve resection and implantation of the proximal
      ends into muscle can give good to excellent results in most patients. CLINICAL
      QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

PMID- 24572862
TI  - Factors influencing fellowship selection, career trajectory, and academic
      productivity among plastic surgeons.
AB  - BACKGROUND: Several factors influence the career trajectory of graduating plastic
      surgeons, and the authors' study sought to capture characteristics of plastic
      surgery trainees as they relate to outcomes, including fellowship selection,
      career choice, and academic productivity. METHODS: Anonymous online survey data
      were obtained from members of the American Society of Plastic Surgeons.
      Correlative analysis was performed implementing the Pearson chi-square test, the
      Mann-Whitney test, and the Kendall tau-b correlation to determine significant
      correlations defined by values of p < 0.05. RESULTS: Of 4543 survey invitations
      sent, a total of 624 plastic surgeons (13.7 percent) completed the study. Greater
      numbers of publications on entering residency (p < 0.05) and on graduating from
      residency (p < 0.0001), stronger perceived mentorship during residency (p <
      0.01), graduating from an integrated program (p < 0.01), and fellowship training
      (p < 0.001) were all correlated with a future career in academia. In addition,
      fellowship training and number of publications during and before residency were
      correlated with eventual academic productivity (p < 0.05). Lastly, individual
      tendency to prioritize economics (p < 0.01) or geographic location (p < 0.05) was
      associated with eventual private practice, whereas prioritization of research (p
      < 0.01) and culture of training institute (p < 0.001) predicted academic careers.
      CONCLUSIONS: Graduating plastic surgery residents from integrated programs, with
      greater numbers of publications, stronger mentor relationships, and fellowship
      training were more likely to become academic surgeons. Among this academic
      cohort, fellowship training and greater numbers of publications before and during
      residency were significantly correlated with increased academic productivity as
      an attending surgeon.

PMID- 24572863
TI  - Discussion: Factors influencing fellowship selection, career trajectory, and
      academic productivity among plastic surgeons.

PMID- 24572864
TI  - Ketorolac does not increase perioperative bleeding: a meta-analysis of randomized
      controlled trials.
AB  - BACKGROUND: Postoperative pain control is essential for optimal patient outcomes.
      Ketorolac is an attractive alternative for achieving pain control
      postoperatively, but concerns over postoperative bleeding have limited its use.
      METHODS: Computer searches of the MEDLINE, EMBASE, and Cochrane Library databases
      were performed. Twenty-seven double-blind, randomized, controlled studies were
      reviewed by two independent investigators for the incidence of adverse events,
      including postoperative bleeding. Comprehensive meta-analysis software was used
      to evaluate the differences between ketorolac and control groups. RESULTS: Twenty
      seven studies with 2314 patients were analyzed. Postoperative bleeding occurred
      in 33 of 1304 patients (2.5 percent) in the ketorolac group compared with 21 of
      1010 (2.1 percent) in the control group (OR, 1.1; 95 percent CI, 0.61 to 2.06; p
      = 0.72). Adverse events were similar in the groups, 31.7 percent in the control
      group and 27.9 percent in the ketorolac group (OR, 0.64; 95 percent CI, 0.41 to
      1.01; p = 0.06). There was a lower incidence of adverse effects with low-dose
      ketorolac (OR, 0.49; 95 percent CI, 0.27 to 0.91; p = 0.02). Pain control with
      ketorolac was superior to controls and equivalent to opioids. CONCLUSIONS: This
      is the first meta-analysis of randomized controlled trials examining whether
      there is increased postoperative bleeding with ketorolac. Postoperative bleeding
      was not significantly increased with ketorolac compared with controls, and
      adverse effects were not statistically different between the groups. Pain control
      was found to be superior with ketorolac compared with controls. Ketorolac should
      be considered for postoperative pain control, especially to limit the use of
      opioid pain medications. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.

PMID- 24572865
TI  - The process of publishing industry-affiliated articles in Plastic and
      Reconstructive Surgery.

PMID- 24572867
TI  - The effect of prior abdominal surgery on abdominally based free flaps in breast
      reconstruction.
AB  - BACKGROUND: The abdomen has long remained the preferred donor site in breast
      reconstruction. Over time, the flap has evolved to limit morbidity with reduced
      muscular harvest. Previous abdominal operations, however, may limit the ability
      to perform a muscle- or fascia-sparing flap. The purpose of this study was to
      evaluate outcomes in women who had prior abdominal operations and underwent
      abdominally based autologous breast reconstruction. METHODS: All patients who
      underwent abdominally based breast free flap reconstruction between 2004 and 2009
      were reviewed. A study group of patients with previous open abdominal surgery
      were compared to patients with no prior abdominal surgery. Patient demographics,
      operative details, and flap and donor-site complications were analyzed. RESULTS:
      A total of 539 patients underwent abdominally based breast free flap
      reconstruction. The study group consisted of 268 patients (341 flaps) and the
      control group consisted of 271 patients (351 flaps). Prior abdominal surgery led
      to greater muscular harvest, as 19.9 percent in the study group versus 12.0
      percent required muscle-sparing 1-type harvest (p < 0.01). Both groups presented
      similar overall complications, with the exception of lower partial flap loss and
      increased wound healing complications in the study group (p < 0.05). Abdominal
      wall laxity became less frequent with increasing number of prior abdominal
      operations. CONCLUSIONS: Abdominally based flaps for breast reconstruction,
      including muscle-sparing 3 (deep inferior epigastric perforator) flaps, can be
      performed safely in patients with prior abdominal surgery. These patients should
      be informed, however, of an increased chance of muscular harvest and wound
      healing complications. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

PMID- 24572868
TI  - Analyzing implant movement with tabbed and nontabbed expanders through the
      process of two-stage breast reconstruction.
AB  - BACKGROUND: Tabbed tissue expanders have the potential benefit of less migration
      during the expansion process, which may allow for more predictable outcomes.
      Despite this theoretical benefit, no study has critically evaluated the proposed
      advantage as compared with traditional nontabbed expanders. Therefore, the
      authors photographically analyzed the migration and movement of tabbed and
      nontabbed expanders throughout the reconstructive process. METHODS: The authors
      performed a retrospective review of patients who underwent two-stage expander-to
      implant reconstruction from 2010 to 2012. Standardized frontal photographs were
      used for analysis. Adobe Photoshop was used to measure the relative movement of
      each patient's expander from insertion until immediately before implant exchange
      and after implant exchange. RESULTS: Forty-four breasts were analyzed. Migration
      was reduced significantly in all four directions for both the tissue expander and
      permanent implant stages of reconstruction. Medial, lateral, superior, and
      inferior migration of the tissue expander in the tabbed cohort was reduced by
      59.5 percent (p = 0.001), 48.3 percent (p = 0.004), 53.4 percent (p = 0.0005),
      and 73.4 percent (p < 0.0001), respectively, compared with the nontabbed cohort.
      Likewise, medial, lateral, superior, and inferior migration of the permanent
      implant in the tabbed cohort was reduced by 44.3 percent (p = 0.049), 73.7
      percent (p < 0.0001), 67.7 percent (p = 0.0008), and 61.0 percent (p = 0.003),
      respectively. CONCLUSIONS: Two-stage implant reconstruction allows for precision
      in implant placement after an appropriately placed expander. Tabbed expanders
      appear to maintain better positioning on the chest wall compared with nontabbed
      expanders during the expansion process, and may allow for more precise mound
      creation with the permanent implant. CLINICAL QUESTION/LEVEL OF EVIDENCE:
      Therapeutic, III.

PMID- 24572869
TI  - Discussion: Analyzing implant movement with tabbed and nontabbed expanders
      through the process of two-stage breast reconstruction.

PMID- 24572870
TI  - Venous thromboembolism risk in mastectomy and immediate breast reconstruction:
      analysis of the 2005 to 2011 American College of Surgeons National Surgical
      Quality Improvement Program data sets.
AB  - BACKGROUND: Venous thromboembolism, including deep venous thrombosis and
      pulmonary embolism, is a morbid and costly complication following surgical
      procedures. The authors aim to assess the added risk of venous thromboembolism in
      patients undergoing immediate breast reconstruction. METHODS: The 2005 to 2011
      American College of Surgeons National Surgical Quality Improvement Program data
      sets were used to identify patients undergoing mastectomy with or without
      immediate breast reconstruction. The dependent variable and our primary outcome
      was 30-day venous thromboembolism. Venous thromboembolism events were treated as
      a dichotomous variable. Subgroup analyses were performed with respect to
      procedure and body mass index stratifications. RESULTS: A total of 48,634
      patients were identified. Postoperative venous thromboembolism occurred in 184
      patients (0.4 percent), including deep venous thrombosis (n = 118) and pulmonary
      embolism (n = 82). A multivariate regression analysis demonstrated that immediate
      breast reconstruction, either implant-based (OR, 1.65; p = 0.01) or autologous
      (OR, 2.14; p = 0.009), was associated with a greater odds of venous
      thromboembolism. Obesity was also identified as a risk factor for venous
      thromboembolism: class I (OR, 2.20; p < 0.001), class II (OR, 1.6; p < 0.092),
      and class III (OR, 2.88; p < 0.001). Impaired patient functional status (OR,
      2.56; p = 0.035), recent irradiation (OR, 3.60; p = 0.03), and underlying renal
      comorbidities (OR, 5.60; p < 0.001) were associated with venous thromboembolism
      in adjusted analysis. Subgroup analysis of nonobese patients demonstrated that
      implant reconstruction (0.2 percent versus 0.3 percent; p = 0.383) did not confer
      an added risk of venous thromboembolism, whereas analysis of obese patients
      revealed a modality-specific increased risk of venous thromboembolism (0.4
      percent versus 0.8 percent versus 1.8 percent; p < 0.001) between mastectomy
      compared to implant and autologous reconstruction, and for which all intergroup
      comparisons were significant (p < 0.05). CONCLUSIONS: Immediate breast
      reconstruction is associated with an added risk of venous thromboembolism
      relative to mastectomy, but this risk is procedure and body mass index dependent.
      Overall, autologous reconstruction and states of obesity placed patients at
      significant added risk for venous thromboembolism, particularly when both factors
      are present. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

PMID- 24572871
TI  - Contouring of the lower face by a novel method of narrowing and lengthening
      genioplasty.
AB  - BACKGROUND: Lower face contouring surgery has become a popular aesthetic
      operation in most East Asian countries. Various surgical methods are used to
      improve lower face aesthetics. However, when a patient has both a short and a
      wide lower face, a chin-lengthening procedure should be performed simultaneously
      with narrowing genioplasty. Autogenous bone grafts or alloplastic materials are
      commonly used to correct this problem, but these surgical methods have several
      inherent disadvantages. To avoid these complications, the authors devised a
      novel, simple, and reliable method that can correct a short and wide lower face.
      METHODS: From January of 2010 to December of 2012, a consecutive series of 58
      patients underwent chin-narrowing and chin-lengthening surgery. First, the newly
      designed narrowing and lengthening genioplasty was performed. Then, the mandible
      lower borders were further contoured to diminish the bony steps at the chin
      mandible junction and achieve a smooth and slender jaw line. RESULTS: All
      patients showed sufficient improvement of their facial contours, and most of the
      patients were satisfied with their surgical outcomes. No severe complications
      were noted during the follow-up period. The results were confirmed with
      postoperative radiographs and medical photographs. CONCLUSIONS: As the lower face
      plays an important role in the aesthetics and balance of the entire face, the
      authors' novel surgical tool to narrow and lengthen the chin can provide
      aesthetically gratifying results when correcting a short and wide lower face.
      Complications seen with previous chin-lengthening methods were avoided, and the
      new surgical tool showed reliable and predictable surgical outcomes. CLINICAL
      QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

PMID- 24572872
TI  - Discussion: Contouring of the lower face by a novel method of narrowing and
      lengthening genioplasty.

PMID- 24572873
TI  - Achieving predictability in augmentation mastopexy.
AB  - BACKGROUND: Augmentation mastopexy remains a procedure wrought with high rates of
      complications and revisions given the diametrically opposing forces in this
      combined procedure. Thus, many surgeons remain cautious and err on a staged
      procedure. This article provides a dependable, predictable, and straightforward
      approach to a challenging operation. The technique centers on five key points,
      including precise preoperative markings, 8-cm vertical limbs with a broad pedicle
      base, limited undermining of thick skin flaps, small subpectoral implants, and
      movement of the nipple no more than 4 cm. METHODS: Eighty-three patients who
      underwent augmentation mastopexy performed by a single surgeon (R.J.R) were
      included in a retrospective chart review following institutional review board
      approval. Information regarding demographics, implant contracture, degree of
      breast ptosis, and standard breast measurements was recorded. Operative data and
      postoperative complications were documented. RESULTS: At a mean follow-up of 38
      months, major complications included 16 revisions and one readmission for
      superficial thrombophlebitis. The majority of revisions were for scar revision or
      implant size change. Minor complications included two hematomas, one seroma,
      three T-point skin sloughs, and two minor infections. There were no instances of
      major flap loss or nipple loss. CONCLUSIONS: The technique described provides a
      safe and conservative surgical approach for one-stage augmentation mastopexy
      resulting in the avoidance of major pitfalls and irreversible complications of
      flap or nipple loss while achieving the desired results of the patient and
      surgeon. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

PMID- 24572874
TI  - Plastic surgery: quo vadis? Current trends and future projections of aesthetic
      plastic surgical procedures in the United States.
AB  - BACKGROUND: The objective of this article was to evaluate past and current trends
      regarding aesthetic operations in the United States and to project future changes
      regarding such procedures. METHODS: Cosmetic surgery statistics from the American
      Society for Aesthetic Plastic Surgery from 1997 to 2012 were analyzed by sex,
      age, and ethnic group. Then, using population projections from the U.S. Census
      Bureau based on the 2010 census, two projection scenarios of the expected number
      of aesthetic plastic surgery procedures were generated. The scenarios included
      the presumed occurrence and nonoccurrence of a recession like that which occurred
      in 2007. RESULTS: Aesthetic procedures are expected to grow from 1,688,694 in
      2012 to 3,847,929 by 2030, representing an average annual growth rate of 7.1
      percent. Should another recession of similar degree to the one in 2007 occur,
      procedures would increase to only 2,086,994, displaying an average annual growth
      percentage rate of 1.3 percent. Because the age distribution of the patient
      population will change, preferences for specific procedures according to age
      influence-and thus are reflected in-future demand for those procedures.
      Furthermore, the ethnic profile of patients will change significantly, with 32
      percent of all procedures being performed on patients other than Caucasians by
      2030. CONCLUSIONS: Demand for aesthetic plastic surgical procedures is expected
      to continue to grow, while depending on the economic performance at the macro
      level and changing demographic dynamics of the U.S. population. Considering all
      investigated factors and trends among all patients, the most commonly requested
      procedures by 2030 are likely to be (1) breast augmentations, (2) lipoplasties,
      and (3) blepharoplasties.

PMID- 24572875
TI  - Degeneration, regeneration, and cicatrization after fat grafting: dynamic total
      tissue remodeling during the first 3 months.
AB  - BACKGROUND: Fat grafting is promising, but clinical outcomes are not always
      predictable. The mechanisms of tissue revascularization/regeneration, and tissue
      necrosis and subsequent absorption/fibrosis of the graft, are poorly understood.
      METHODS: An autologous inguinal fat pad was transplanted under the scalp of mice,
      and detailed cellular events during the first 3 months were investigated with
      immunohistochemistry. RESULTS: Except for the most superficial surviving zone,
      death of all adipocytes was confirmed at 1 week. Perilipin-positive small new
      adipocytes appeared at 1 week and peaked in number at 4 weeks in the regenerating
      zone (the second zone). In the most central necrotizing zone, adipogenesis did
      not occur and many inflammatory cells were observed after 2 weeks. CD34+/Ki67+
      proliferating adipose stem/progenitor cells were seen at 1 to 4 weeks, but the
      majority of proliferating cells were MAC2+ monocytes/macrophages. Although CD206+
      M1 macrophages surrounded oil droplets for phagocytosis, CD206+ M2 macrophages
      appeared in areas where adipocyte replacement failed and formed multiple layers
      for cicatrization of oil drop spaces. Adipogenesis was complete by 12 weeks, but
      stabilization of nonregenerated areas was still ongoing at that time. Lipid
      droplets derived from dead adipocytes were absorbed slowly and thus aided adipose
      remodeling by maintaining the space until adipocyte regeneration. CONCLUSIONS:
      Dynamic remodeling after fat grafting was confirmed. Adipocyte fate differed,
      depending on the microenvironment: intact survival, replacement with a new
      adipocyte, or replacement with cicatrization/oil cyst. This detailed
      understanding will help refine surgical grafting procedures and postoperative
      evaluation.

PMID- 24572877
TI  - Discussion: Prophylactic amifostine preserves the biomechanical properties of
      irradiated bone in the murine mandible.

PMID- 24572876
TI  - Prophylactic amifostine preserves the biomechanical properties of irradiated bone
      in the murine mandible.
AB  - BACKGROUND: The authors have previously demonstrated that amifostine prophylaxis
      mitigates the pernicious effects of radiation in settings of fracture repair and
      distraction osteogenesis. Expanding on these studies, the authors examined the
      biomechanical properties of uninjured bone exposed to both radiation and
      amifostine. The authors hypothesize that radiation will degrade the biomechanical
      properties of native bone, and further hypothesize that prophylactic amifostine
      will preserve biomechanical properties to levels of normal bone and protect
      against radiation-induced morbidities. METHODS: Rats were randomized into
      control, irradiated, and amifostine pretreatment plus radiation (amifostine
      pretreated) groups. Irradiated animals received a fractionated dosing schedule of
      35 Gy, with amifostine-pretreated animals receiving amifostine before
      irradiation. Hemimandibles were harvested at 8 and 18 weeks for biomechanical
      testing and micro-computed tomographic analysis. RESULTS: At 8 weeks, irradiated
      specimens displayed elevations above controls for all biomechanical properties.
      At 18 weeks, the biomechanical properties of irradiated specimens degraded in
      comparison with controls; at both time points, amifostine-pretreated specimens
      were maintained at levels comparable to controls. There was a significant
      decrease in tissue mineral density from 8- to 18-week irradiated specimens,
      whereas no such change existed for control and amifostine-pretreated specimens.
      CONCLUSIONS: The authors' findings demonstrate paradoxical and transient
      elevations in the initial biomechanical properties of irradiated specimens that
      were not sustained through the later study time point. Amifostine pretreatment,
      however, provided uninterrupted preservation of the biomechanical properties of
      normal, native bone at both time points. This supports the contention that
      amifostine is capable of providing continuous protection to bone against the
      untoward effects of radiation therapy.

PMID- 24572878
TI  - Traumatic orbital roof fractures: interdisciplinary evaluation and management.
AB  - BACKGROUND: The orbital roof forms part of the anterior skull base and is
      positioned for potential concomitant ophthalmologic and neurologic injury.
      Despite potential morbidity and mortality, orbital roof fractures have garnered
      little attention compared with orbital floor fractures. The authors' purpose is
      to review and describe key points when treating these fractures. METHODS: The
      authors reviewed 1171 consecutive patient at a trauma center with orbital or
      skull base fractures from 2009 to 2011. Patient demographics, mechanism of
      injury, associated injuries, treatment, outcomes, and complications were
      recorded. RESULTS: Among the 1171 patients, the authors identified 60 with an
      orbital roof fracture (5 percent). All were evaluated by plastic surgery,
      neurosurgery, and ophthalmology. Average age was 38.1 years, and the male-to
      female ratio was 4:1. Frequent mechanisms of injury were fall (33 percent),
      followed by assault (25 percent). Concomitant craniofacial skeletal fractures
      were common (87 percent), as were ophthalmologic injuries (47 percent), and
      traumatic brain injury with intracranial hemorrhage (65 percent). Six patients
      (10 percent) required operative repair of the orbital roof, all of whom had a
      dural laceration and cerebrospinal fluid leak. Most patients (90 percent) had
      minimal displacement and no clinically evident cerebrospinal fluid leak and were
      treated with observation without complications. CONCLUSIONS: Orbital roof
      fractures are a less common but potentially serious craniofacial injury. Most can
      be safely observed; however, intracranial or intraorbital injury may warrant
      surgical intervention to remove impinging bony fragments, repair dura, or
      reconstruct the orbital roof. An interdisciplinary approach with plastic surgery,
      ophthalmology, and neurosurgery is crucial to providing comprehensive care.
      CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

PMID- 24572879
TI  - Expression of follicle-stimulating hormone receptor in vascular anomalies.
AB  - BACKGROUND: The mechanism for the growth of infantile hemangioma and vascular
      malformations is unknown. Follicle-stimulating hormone secretion mirrors the life
      cycle of infantile hemangioma and increases during adolescence, when vascular
      malformations often progress. The purpose of this study was to determine whether
      vascular anomalies express the receptor for follicle-stimulating hormone.
      METHODS: Human vascular tumors (i.e., infantile hemangioma, congenital
      hemangioma, kaposiform hemangioendothelioma, and pyogenic granuloma) and vascular
      malformations (i.e., capillary, lymphatic, venous, and arteriovenous) were
      subjected to immunofluorescence for follicle-stimulating hormone receptor.
      Control specimens included normal skin/subcutis, mucosa, liver, spleen, Crohn
      disease, granulation, pancreatitis, rheumatoid arthritis, and synovitis. Receptor
      and microvessel density were quantified using imaging software. RESULTS: Follicle
      stimulating hormone receptor was found in the endothelium of all vascular
      anomalies but was not present in control specimens. Expression was greater in
      proliferating infantile hemangioma (6.0 percent) compared with other vascular
      tumors (congenital hemangioma, 0.61 percent; kaposiform hemangioendothelioma,
      0.55 percent; pyogenic granuloma, 0.56 percent; p < 0.0001), despite similar
      microvessel density (p = 0.1). Follicle-stimulating hormone receptor was elevated
      in arteriovenous malformations (2.65 percent) compared with other types of
      vascular malformations (capillary, 1.02 percent; lymphatic, 0.38 percent; venous,
      0.76 percent; p < 0.0001). CONCLUSIONS: Vascular anomalies express follicle
      stimulating hormone receptor on their endothelium, in contrast to vascular
      control tissues. Vascular anomalies are the only benign, pathologic tissue known
      to express this receptor. Because the secretion of follicle-stimulating hormone
      correlates with the growth pattern of infantile hemangioma and vascular
      malformations, follicle-stimulating hormone might be involved in the pathogenesis
      of these lesions.

PMID- 24572880
TI  - The effectiveness of mandibular distraction in improving airway obstruction in
      the pediatric population.
AB  - BACKGROUND: Distraction osteogenesis is an effective technique for elongating the
      deficient mandible. The authors specifically evaluated its effectiveness in the
      treatment of airway obstruction in pediatric patients with mandibular hypoplasia.
      METHOD: A comprehensive literature review of the National Library of Medicine
      (PubMed) database was performed. English-language studies involving isolated
      distraction of the pediatric mandible (younger than 18 years) with descriptive
      reporting of airway changes were included. Extracted data included demographics,
      initial diagnosis, distractor type, distraction protocol, predistraction and
      postdistraction airway status, and complications. RESULTS: Seventy-four articles
      met the inclusion criteria, resulting in 711 patients with craniofacial
      abnormalities who underwent mandibular distraction osteogenesis. Mean age at the
      time of distraction was 18.1 months. The most common diagnoses were isolated
      Pierre Robin sequence (52.9 percent), syndromic Pierre Robin sequence (7
      percent), and Treacher Collins syndrome (6.8 percent). Mandibular distraction
      osteogenesis successfully treated airway obstruction in 89.3 percent of cases.
      Success was defined as either decannulation of tracheostomy, avoidance of
      tracheostomy or continuous positive airway pressure, or alleviation or
      significant improvement of obstructive sleep apnea symptoms. One hundred seventy
      one (84.2 percent) of the 203 tracheostomy-dependent patients were successfully
      decannulated. Among the 181 patients with obstructive sleep apnea, mandibular
      distraction osteogenesis successfully allowed for either complete resolution or
      significant improvement of symptoms in 95.6 percent. A 23.8 percent overall
      complication rate was noted. The mean follow-up time was 28.7 months. CONCLUSION:
      In addition to its positive effect on facial appearance, mandibular distraction
      osteogenesis is an effective procedure for the treatment of airway obstruction
      associated with congenital craniofacial defects involving mandibular hypoplasia
      in appropriately selected patients.

PMID- 24572881
TI  - Auricular reconstruction using tissue-engineered alloplastic implants for
      improved clinical outcomes.
AB  - BACKGROUND: Alloplastic implants have been used clinically to treat congenital
      abnormalities and traumatic injuries. However, these implants are often
      associated with complications, including inflammation, infection, erosion, and
      dislodgment. To minimize these complications, the authors have developed a system
      in which tissue-engineered cartilage serves as a shell that entirely covers the
      implant. This system is designed to improve the structural and functional
      stability between the implant and recipient tissue. METHODS: Chondrocytes
      isolated from rabbit ear cartilage were expanded in vitro. The cells were mixed
      with fibrin hydrogel for spray-coating a human ear-shaped implant. The surface of
      the implant was modified using an oxidizing solution to provide hydrophilic
      characteristic; thus, the cell-fibrin suspension readily adhered onto the surface
      of the implants. The engineered cartilage-covered implants were implanted into
      the dorsal subcutaneous space of athymic mice. Histologic and gross examinations
      of the implants were performed at 2, 4, 8, and 12 weeks after implantation.
      RESULTS: None of the engineered cartilage-covered implants showed evidence of
      skin necrosis, implant exposure, or extrusion (n = 10). However, the control
      implants developed extensive necrosis following implantation (n = 10). In the
      experimental group, histologic evaluations showed the formation of neocartilage
      covering the implants. The presence of sulfated glycosaminoglycans was evident in
      the engineered cartilage tissue. CONCLUSIONS: These results demonstrate that
      engineered cartilage tissues can be used as a biological cover for an alloplastic
      implant. This system may improve the structural and functional interactions
      between the implant and the recipient's tissues and thus enhance the outcome of
      total auricular reconstruction.

PMID- 24572882
TI  - Management of hidradenitis suppurativa wounds with an internal vacuum-assisted
      closure device.
AB  - BACKGROUND: Hidradenitis suppurativa is a chronic, debilitating disease that is
      difficult to treat. Once medical management fails, wide local excision offers the
      best chance for cure. However, the resultant wound often proves too large or
      contaminated for immediate closure. METHODS: The authors performed a
      retrospective chart review of hidradenitis cases managed surgically between 2005
      and 2010. Data collected included patient characteristics, management method, and
      outcomes. Approximately half of the patients received internal vacuum-assisted
      closure therapy using the vacuum-assisted closure system and delayed closure and
      half of the patients received immediate primary closure at the time of their
      excision. Delayed closure consisted of closing the majority of the wound in a
      linear fashion following internal vacuum-assisted closure while accepting healing
      by means of secondary intention for small wound areas. RESULTS: Patients managed
      with internal vacuum-assisted closure had wounds on average four times larger in
      area than patients managed without internal vacuum-assisted closure. In both
      groups, all wounds were eventually closed primarily. Healing times averaged 2.2
      months with internal vacuum-assisted closure and 2.7 months without. At an
      average follow-up time of 2.3 months, all patients with internal vacuum-assisted
      closure had no recurrence of their local disease. CONCLUSIONS: Severe
      hidradenitis presents a treatment challenge, as surgical excisions are often
      complicated by difficult closures and unsatisfactory recurrence rates. This study
      demonstrates that wide local excision with reasonable outcomes can be achieved
      using accelerated delayed primary closure. This method uses internal vacuum
      assisted closure as a bridge between excision and delayed primary closure,
      facilitating closure without recurrence in large, heavily contaminated wounds.
      CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

PMID- 24572883
TI  - Donor-site preferences in women during autologous skin grafting.
AB  - BACKGROUND: Autologous split-thickness skin grafting has been proven to provide
      the best cosmetic and functional outcome after cutaneous burn injuries and thus
      is the standard of care. Clinical observations have shown that female burn
      patients frequently have greater difficulty choosing a donor site than do male
      burn patients. However, there is a lack of data characterizing donor-site
      preferences among women with burns. METHODS: The purpose of this study was to
      examine donor-site preferences among women using an online survey that included
      356 responders between January 4, 2012, and April 4, 2012. RESULTS: This study
      found that there was a preference for posterior donor sites, with lower back,
      left buttock, and left posterior thigh being the most preferred sites. The least
      preferred locations were the right anterior upper arm, any aspect of the
      forearms, and the chest. Those surveyed and reporting a higher education level or
      concerns with scarring were least likely to choose anterior locations. Age,
      concern for color changes, and prior surgery or grafting had no statistically
      significant effect on donor-site preference. CONCLUSION: Given these strong
      preferences among female patients, posterior donor sites should be considered and
      discussed as compared with the current standard of using lateral or anterior
      thigh donor sites.

PMID- 24572884
TI  - Wound healing: part II. Clinical applications.
AB  - Treatment of all wounds requires adequate wound bed preparation, beginning with
      irrigation and debridement. Complicated or chronic wounds may also require
      treatment adjuncts or specialized wound healing products. An extensive body of
      research and development has introduced novel wound healing therapies and scar
      management options. In this second of a two-part continuing medical education
      series on wound healing, the reader is offered an update on current wound healing
      technologies and recommendations for obtaining optimal outcomes.

PMID- 24572885
TI  - Academic plastic surgery: faculty recruitment and retention.
AB  - BACKGROUND: A critical element of a thriving academic plastic surgery program is
      the quality of faculty. A decline in recruitment and retention of faculty has
      been attributed to the many challenges of academic medicine. Given the
      substantial resources required to develop faculty, academic plastic surgery has a
      vested interest in improving the process of faculty recruitment and retention.
      METHODS: The American Council of Academic Plastic Surgeons Issues Committee and
      the American Society of Plastic Surgeons/Plastic Surgery Foundation Academic
      Affairs Council surveyed the 83 existing programs in academic plastic surgery in
      February of 2012. The survey addressed the faculty-related issues in academic
      plastic surgery programs over the past decade. Recruitment and retention
      strategies were evaluated. This study was designed to elucidate trends, and
      define best strategies, on a national level. RESULTS: Academic plastic surgery
      programs have added substantially more full-time faculty over the past decade.
      Recruitment efforts are multifaceted and can include guaranteed salary support,
      moving expenses, nurse practitioner/physician's assistant hires, protected time
      for research, seed funds to start research programs, and more. Retention efforts
      can include increased compensation, designation of a leadership appointment,
      protected academic time, and call dilution. CONCLUSIONS: Significant change and
      growth of academic plastic surgery has occurred in the past decade. Effective
      faculty recruitment and retention are critical to a successful academic center.
      Funding sources in addition to physician professional fees (institutional program
      support, grants, contracts, endowment, and so on) are crucial to sustain the
      academic missions.

PMID- 24572886
TI  - Discussion: Academic plastic surgery: faculty recruitment and retention.

PMID- 24572887
TI  - Characterization of the digestive tract microbiota of Hirudo orientalis
      (medicinal leech) and antibiotic resistance profile.
AB  - BACKGROUND: There are at least three distinct European leech species used
      medicinally: Hirudo medicinalis, H. orientalis, and H. verbana. Infection caused
      by leech microbiota is the most widely reported complication. Few studies have
      reported the culturable and unculturable bacteria and examined the antibiotic
      resistances in H. orientalis. METHODS: Following stratified random sampling from
      a major worldwide leech supplier, Hirudo orientalis leeches were identified by
      visual comparison and amplification and sequencing the cox1 locus. Combined
      culture and culture-independent approaches were used to characterize the
      microbiota of the midgut, and bacterial gyrB sequences from distinct colonies
      were used to identify the Aeromonas isolates. Nonculturable studies involved
      clone libraries of 16S rRNA genes, and Etests were used to investigate antibiotic
      sensitivities. RESULTS: Analysis of 16S rRNA gene clone libraries revealed the
      presence of several species in the intraluminal fluid of the crop, including a
      new finding of Morganella morganii, with Rikenella-like (35 percent) and
      Aeromonas veronii (38 percent) dominant members. The intestinum contained
      bacteria not previously isolated from the leech: Magnetospirillium species and
      Roseospira marina. Etests showed all A. veronii isolates were sensitive to
      ciprofloxacin, with either a complete or intermediate resistance to Augmentin.
      CONCLUSIONS: The authors show diverse microbiota in the leech digestive tract.
      The pathogenic potential of the additional gut symbionts isolated in this study
      is yet to be elucidated; however, M. morganii, which is a known human pathogen,
      is a new finding. In addition to adding to the knowledge base regarding
      antibiotic sensitivities, this article serves as an update to the reconstructive
      surgeon regarding leech therapy.

PMID- 24572888
TI  - The effect of pressure and shear on autologous fat grafting.

PMID- 24572889
TI  - Reply: The effect of pressure and shear on autologous fat grafting.

PMID- 24572890
TI  - A process for quantifying aesthetic and functional breast surgery: I. Quantifying
      optimal nipple position and vertical and horizontal skin excess for mastopexy and
      breast reduction.

PMID- 24572891
TI  - Reply: A process for quantifying aesthetic and functional breast surgery: I.
      Quantifying optimal nipple position and vertical and horizontal skin excess for
      mastopexy and breast reduction.

PMID- 24572892
TI  - Effects of CB-VEGF-A injection in rat flap models for improved survival.

PMID- 24572893
TI  - Reply: Effects of CB-VEGF-A injection in rat flap models for improved survival.

PMID- 24572894
TI  - Mechanisms of action of external volume expansion devices.

PMID- 24572895
TI  - Reply: Mechanisms of action of external volume expansion devices.

PMID- 24572896
TI  - Vascularized groin lymph node flap transfer for postmastectomy upper limb
      lymphedema: flap anatomy, recipient sites, and outcomes.

PMID- 24572897
TI  - Reply: Vascularized groin lymph node flap transfer for postmastectomy upper limb
      lymphedema: the flap anatomy, recipient sites, and outcomes.

PMID- 24572898
TI  - The Children's Hospital of Philadelphia modification of the Furlow double
      opposing Z-palatoplasty: 30-year experience and long-term speech outcomes.

PMID- 24572899
TI  - Reply: The Children's Hospital of Philadelphia modification of the Furlow double
      opposing Z-palatoplasty: 30-year experience and long-term speech outcomes.

PMID- 24572900
TI  - Free-style local perforator flaps: versatility of the V-Y design to reconstruct
      soft-tissue defects in the skin cancer population.

PMID- 24572901
TI  - Reply: Free-style local perforator flaps: versatility of the V-Y design to
      reconstruct soft-tissue defects in the skin cancer population.

PMID- 24572902
TI  - Soft-tissue coverage of the elbow.

PMID- 24572903
TI  - Managing malignant melanoma.

PMID- 24572904
TI  - Augmentation mammaplasty after breast enhancement with macrolane.

PMID- 24572905
TI  - A fascial band implicated in Wartenberg syndrome.

PMID- 24572907
TI  - Gossypiboma: an approach to diagnosis in the era of medical tourism.

PMID- 24572906
TI  - Reconstruction of extensive defects with combined transverse-vertical rectus
      abdominis (cruciate) myocutaneous flaps.

PMID- 24572908
TI  - The effect of flap coverage on length of stay and costs for patients with
      fractures of the tibia.

PMID- 24572909
TI  - When can social media lead financial markets?
AB  - Social media analytics is showing promise for the prediction of financial
      markets. However, the true value of such data for trading is unclear due to a
      lack of consensus on which instruments can be predicted and how. Current
      approaches are based on the evaluation of message volumes and are typically
      assessed via retrospective (ex-post facto) evaluation of trading strategy
      returns. In this paper, we present instead a sentiment analysis methodology to
      quantify and statistically validate which assets could qualify for trading from
      social media analytics in an ex-ante configuration. We use sentiment analysis
      techniques and Information Theory measures to demonstrate that social media
      message sentiment can contain statistically-significant ex-ante information on
      the future prices of the S&P500 index and a limited set of stocks, in excess of
      what is achievable using solely message volumes. 

PMID- 24572911
TI  - Renin-angiotensin system blockade and pleiotropic cardiovascular effects: the
      novel angiotensin receptor blocker azilsartan.

PMID- 24572910
TI  - An antagonistic interaction between PlexinB2 and Rnd3 controls RhoA activity and
      cortical neuron migration.
AB  - A transcriptional programme initiated by the proneural factors Neurog2 and Ascl1
      controls successive steps of neurogenesis in the embryonic cerebral cortex.
      Previous work has shown that proneural factors also confer a migratory behaviour
      to cortical neurons by inducing the expression of the small GTP-binding proteins
      such as Rnd2 and Rnd3. However, the directionality of radial migration suggests
      that migrating neurons also respond to extracellular signal-regulated pathways.
      Here we show that the Plexin B2 receptor interacts physically and functionally
      with Rnd3 and stimulates RhoA activity in migrating cortical neurons. Plexin B2
      competes with p190RhoGAP for binding to Rnd3, thus blocking the Rnd3-mediated
      inhibition of RhoA and also recruits RhoGEFs to directly stimulate RhoA activity.
      Thus, an interaction between the cell-extrinsic Plexin signalling pathway and the
      cell-intrinsic Ascl1-Rnd3 pathway determines the level of RhoA activity
      appropriate for cortical neuron migration. 

PMID- 24572912
TI  - Prediction of treatment-induced changes in target-organ damage using changes in
      clinic, home and ambulatory blood pressure.
AB  - Cross-sectional studies have shown that ambulatory and home blood pressure (ABP
      and HBP, respectively) measurements are more closely associated with preclinical
      organ damage than are office measurements. This study investigated the
      association between treatment-induced changes in BP assessed by the three methods
      and the corresponding changes in organ damage. Untreated hypertensives were
      evaluated with office, ABP and HBP measurements and indices of organ damage
      (echocardiographic left-ventricular mass index (LVMI), pulse wave velocity (PWV),
      albuminuria) before and after 12 months of treatment. A total of 116 subjects
      completed the study (mean age 50.7+/-10.5 years, 69 men (59%), mean follow-up
      13.4+/-1.4 months). The treatment-induced change in the LVMI was correlated with
      changes in BP and pulse pressure (PP) assessed by all methods. The change in PWV
      was correlated with changes in home systolic and ABP and PP and with the change
      in home diastolic BP. Albuminuria showed no correlations. In linear regression
      models, changes in home BP and PP had the strongest predictive ability for the
      change in the LVMI, whereas the change in ABP was the strongest predictor of the
      change in PWV. The change in office BP had no predictive value. HBP and ABP
      measurements appear to be superior to office BP measurements and should be
      considered complementary rather than interchangeable methods for monitoring the
      effects of antihypertensive treatment on target-organ damage. 

PMID- 24572913
TI  - Antithrombotic effects of losartan in patients with hypertension complicated by
      atrial fibrillation: 4A (Angiotensin II Antagonist of platelet Aggregation in
      patients with Atrial fibrillation), a pilot study.
AB  - Angiotensin receptor blockers (ARBs) are widely used for the treatment of
      hypertension. It has been reported that the ARB losartan has antiplatelet,
      anticoagulant and profibrinolytic effects experimentally. These properties could
      be desirable to treat hypertensive patients with high atherothrombotic and/or
      thromboembolic risk. To examine the antithrombotic effects of losartan in
      hypertension, 20 consecutive patients with hypertension complicated by atrial
      fibrillation (AF) were enrolled in this study. The patients were treated with
      losartan 50 mg for 8 weeks followed by 100 mg for 4 weeks. Blood samples were
      obtained from each patient at 0 (pretreatment), 8 and 12 weeks after initiating
      treatment. Platelet aggregability, plasma levels of tissue factor (TF) and type 1
      plasminogen activator inhibitor (PAI-1) activity levels were measured. The area
      under the curve for small platelet aggregability decreased from 100 to 42.8% at
      12 weeks (P<0.0001). TF levels (ng ml(-1)) and PAI-1 activity (IU ml(-1); mean+/
      s.d.) also changed from 14.2+/-3.6 to 10.9+/-4.5 at 12 weeks (P=0.0299) and from
      11.7+/-3.6 to 8.5+/-3.1 at 12 weeks (P=0.0122), respectively. Losartan inhibited
      platelet activity and coagulation factors in a dose- and time-dependent manner in
      patients with hypertension complicated by AF, whereas the fibrinolytic capacity
      was increased. The use of losartan could be advantageous in the treatment of
      hypertensive patients with high atherothrombotic risk. 

PMID- 24572914
TI  - Neuroadrenergic disarray in pseudo-resistant and resistant hypertension.
AB  - Several studies have investigated the behavior of sympathetic cardiovascular
      drive in essential hypertension, providing conclusive evidence of the adrenergic
      activation characterizing this condition. These studies have also shown the
      importance of neuroadrenergic overdrive in the development and progression of the
      hypertensive state as well as in the pathogenesis of hypertension-related end
      organ damage. The information available on the sympathetic nervous system's
      behavior in 'pseudo-resistant' and 'true resistant' hypertension is much more
      scarce. This paper will review the available knowledge on this issue by examining
      the data collected via indirect and direct approaches to investigate adrenergic
      function in resistant hypertension as well as the effects of pharmacological and
      non-pharmacological interventions. 

PMID- 24572915
TI  - The neurophysiology of pain: a clinical summary.

PMID- 24572916
TI  - Systematic assessment of impairment and residual functional capacity in pain
      impaired patients.

PMID- 24572917
TI  - Psychological Factors in the Assessment of Disability among Patients with Chronic
      Pain.
AB  - A number of self report, interview, and behavioral measures have been developed
      relevant to disability assessment. This paper reviews those measures and the
      psychological factors that have been studied in relation to those measures. In
      order to facilitate a systematic review of this research, the research is
      organized along lines suggested by the Glasgow Illness Model: (1) research
      associated with physical findings is reviewed first; (2) personality, emotional,
      and cognitive factors are examined as they relate to disability; (3) relations
      between illness behaviors and disability are studied; (4) social factors relevant
      to the sick role (compensation status, family dynamics) are reviewed. Patterns
      among the findings and suggestions for future research are discussed. 

PMID- 24572918
TI  - The multidisciplinary management of the chronic pain patient.

PMID- 24572919
TI  - Interdisciplinary Treatment of Musculoskeletal Pain: The EMPOWER Program.
AB  - Many individuals who experience chronic pain are able to return to work in some
      capacity but continue to suffer from ongoing pain problems resulting in increased
      absenteeism and reduced productivity on the job. These individuals continue to
      require ongoing medical interventions. Monthly follow-up visits to a physician
      rarely provide effective treatment strategies that patients can use at home. The
      challenge is to develop an effective and inexpensive treatment program that will
      assist patients in regaining or maintaining employment and decrease reliance on
      health care facilities. A program of this type has been developed for chronic
      pain sufferers, primarily those with low back and cervical spine pain. The
      treatment is a six-week interdisciplinary program including relaxation training,
      gradually increasing exercise, and significant education on behavioral and
      exercise strategies and nutrition for long-term pain management. This program is
      inexpensive, cost efficient, and may be implemented easily in a variety of
      settings. 

PMID- 24572920
TI  - Pro: impairment listing for pain in social security disability determination.

PMID- 24572921
TI  - Con: impairment listing for pain in social security disability determination.

PMID- 24572922
TI  - Case management: a clinical or sales function?

PMID- 24572923
TI  - The need for redefining chronic pain programs for the injured worker population.

PMID- 24572924
TI  - Point/Counterpoint: a response to redefining chronic pain programs for the
      injured worker population.

PMID- 24572926
TI  - From the editor.

PMID- 24572927
TI  - Exploring trade-offs between air pollutants through an Integrated Assessment
      Model.
AB  - When designing air pollution reduction policies, regional decision makers face a
      limited budget to choose the most efficient measures which will have impacts on
      several pollutants in different ways. RIAT+ is a regional integrated assessment
      tool that supports the policy maker in this selection of the optimal emission
      reduction technologies, to improve air quality at minimum costs. In this paper,
      this tool is formalized and applied to the specific case of a French region
      (Alsace), to illustrate how focusing on one single pollutant may exacerbate
      problems related to other pollutants, on top of conflicts related to budget
      allocation. In our case, results are shown for possible trade-offs between NO2
      and O3 control policies. The paper suggests an approach to prioritize policy
      maker objectives when planning air pollution policies at regional scale. 

PMID- 24572929
TI  - Theoretical and experimental evidences of medium range atmospheric transport
      processes of polycyclic musk fragrances.
AB  - This study investigates some aspects of the environmental fate of galaxolide
      (HHCB) and tonalide (AHTN) musk fragrances, paying particular attention to the
      phenomenon of atmospheric transport of these substances. The problem was
      addressed theoretically and experimentally. Firstly, the application of a
      multimedia model allowed the analysis of their potential atmospheric transport.
      The obtained results argued in favor of a possible phenomenon of medium range
      atmospheric transport for both substances. These theoretical findings were
      supported by the experimental results, which showed their presence both in the
      fresh fallen snow and in water samples taken from the Frodolfo, a glacial stream
      that originates from the Forni Glacier (Alps, Northern Italy). Furthermore, the
      analysis of the air back-trajectories highlighted the prevalence of air masses of
      local origins that reached the sampling area passing through a densely
      anthropized area of Northern Italy. Finally, the experimental results discussed
      here gave evidences of accumulation of these two compounds in the glacier. 

PMID- 24572928
TI  - Life cycle assessment of camelina oil derived biodiesel and jet fuel in the
      Canadian Prairies.
AB  - This study evaluated the environmental impact of biodiesel and hydroprocessed
      renewable jet fuel derived from camelina oil in terms of global warming
      potential, human health, ecosystem quality, and energy resource consumption. The
      life cycle inventory is based on production activities in the Canadian Prairies
      and encompasses activities ranging from agricultural production to oil extraction
      and fuel conversion. The system expansion method is used in this study to avoid
      allocation and to credit input energy to co-products associated with the products
      displaced in the market during camelina oil extraction and fuel processing. This
      is the preferred allocation method for LCA analysis in the context of most
      renewable and sustainable energy programs. The results show that greenhouse gas
      (GHG) emissions from 1 MJ of camelina derived biodiesel ranged from 7.61 to 24.72
      g CO2 equivalent and 3.06 to 31.01 kg CO2/MJ equivalent for camelina HRJ fuel.
      Non-renewable energy consumption for camelina biodiesel ranged from 0.40 to 0.67
      MJ/MJ; HRJ fuel ranged from -0.13 to 0.52 MJ/MJ. Camelina oil as a feedstock for
      fuel production accounted for the highest contribution to overall environmental
      performance, demonstrating the importance of reducing environmental burdens
      during the agricultural production process. Attaining higher seed yield would
      dramatically lower environmental impacts associated with camelina seed, oil, and
      fuel production. The lower GHG emissions and energy consumption associated with
      camelina in comparison with other oilseed derived fuel and petroleum fuel make
      camelina derived fuel from Canadian Prairies environmentally attractive.

PMID- 24572930
TI  - Small-scale passive emission chamber for screening studies on monoterpene
      emission flux from the surface of wood-based indoor elements.
AB  - Analysis of literature data published in the last few years leads to the
      conclusion that in the process of assessment of emission flux of organic
      compounds emitted from different types of equipment and finishing materials, new
      types of devices, among which small-scale passive emission chambers for the
      performance of in-situ research are designed and applied on a larger scale. These
      devices can be successfully used for the assessment of emission flux of organic
      compounds in any location of an apartment, with no interference with its normal
      exploitation. In the following article the possibility of application of a
      designed and constructed small-scale passive emission chamber for the evaluation
      of emission flux of organic compounds (mainly monoterpenes) emitted from the
      surface of wood-based material made of laminated chipboard has been presented.
      The emission chamber made from polished stainless steel of the inner volume of
      3.65 dm(3) allows for the examination/assessment of emission flux from the
      surface of 452 cm(2). A diffusive passive sampler was installed inside of the
      small-scale chamber, which enables collecting samples of the analytes emitted
      from the examined surface of indoor material. The working time of the passive
      emission chamber equaled 300 min. The results of preliminary studies show that,
      the constructed device can be successfully used for screening studies, related
      with the determination of emission flux of monoterpenes from any type of wood
      based flat surface located indoors.

PMID- 24572931
TI  - Comment on the new guidelines in USA by the JAS guidelines committee.

PMID- 24572933
TI  - Clinical presentation and treatment considerations of a ruptured posterior spinal
      artery pseudoaneurysm.
AB  - Spinal artery pseudoaneurysms are rare vascular lesions with poorly defined
      natural history, diagnostic paradigms, and treatment strategies. We present a 68
      year-old woman with severe back pain and left lower extremity weakness with
      spinal subarachnoid hemorrhage due to a ruptured T5 region posterior spinal
      artery pseudoaneurysm, and review issues related to radiologic diagnosis and
      endovascular and open neurosurgical interventions. 

PMID- 24572934
TI  - The first case of an actinide polyrotaxane incorporating cucurbituril: a unique
      'dragon-like' twist induced by a specific coordination pattern of uranium.
AB  - In situ assembly of a cucurbituril-based pseudorotaxane and a uranyl nitrate
      precursor under hydrothermal conditions affords the first actinide polyrotaxane
      with a unique 'dragon-like' twist, which is induced by the specific coordination
      pattern of uranium and stabilized by hydrogen bonding between the eta(1)-mode
      carboxylate group and adjacent methylene moieties of CB[6]. 

PMID- 24572935
TI  - Implementation of recommendations for hand eczema through a multifaceted
      strategy. A process evaluation among health care workers.
AB  - Process data give important insights into how an intervention is implemented. The
      aim of the present study is to conduct a process evaluation, alongside a
      randomised controlled trail, on the implementation of recommendations for the
      prevention of hand eczema. The intervention was carried out in healthcare
      workers' departments and consisted of working groups and role models. The role
      models were selected based on their representativeness, their influence on
      colleagues, and their motivation. The focus of the working group was to implement
      recommendations for hand eczema at the department by choosing solutions to
      overcome barriers for implementation. Out of the 104 solutions, 87 were realised.
      Solutions regarding moisturisers and use of cotton under gloves, were used by
      90.9% and 30.8% of the employees, respectively. Of all participants, 58.2%
      actively engaged with the role models. This process evaluation showed that the
      intervention was executed according to protocol and that the solutions were
      implemented well. However, the role model component in the intervention should be
      improved. 

PMID- 24572936
TI  - Early (before 6 months), late (6-12 months) and very late (after 12 months)
      angiographic scaffold restenosis in the ABSORB Cohort B trial.
AB  - AIMS: The long-term follow-up of the first-in-man ABSORB Cohort B trial showed
      that angiographic binary restenosis can occur early, late or very late after
      implantation of the Absorb everolimus-eluting bioresorbable vascular scaffold
      (Absorb BVS). Since the mechanical support of the scaffold decreases during
      bioresorption, the mechanism of in-segment restenosis (ISR) of the Absorb BVS
      might be different from that of metallic stents. The objective of the current
      analysis was to review the multimodality imaging of cases with binary restenosis
      to elucidate the mechanism of ISR after Absorb BVS implantation. METHODS AND
      RESULTS: The ABSORB Cohort B trial enrolled 101 patients with a maximum of two de
      novo coronary lesions. At the three-year imaging and clinical follow-up, there
      were six cases of in-segment binary restenosis: two early ISR (<6 months), one
      late ISR (6-12 months) and three very late ISR (>12 months). Three of these ISR
      cases seemed to be induced by anatomical or procedural factors. In the other
      three cases, intravascular imaging (IVUS/OCT) demonstrated that the main
      mechanism of restenosis was significant intra-scaffold tissue growth, while the
      structural circularity and diameter of the scaffold were not affected.
      CONCLUSIONS: Early and late restenosis after implantation of the Absorb
      bioresorbable scaffold could be related to anatomical or procedural factors. In
      this small cohort of patients late or very late restenosis seems to be attributed
      to pure intra-scaffold tissue growth without extrinsic encroachment of the
      scaffold.

PMID- 24572938
TI  - From the editor.

PMID- 24572939
TI  - Low back pain.

PMID- 24572937
TI  - New fluorescent sensor for Cu(2+) and S(2-) in 100% aqueous solution based on
      displacement approach.
AB  - An On-Off-On type fluorescent sensor (HL) has been developed, which exhibited
      high selectivity and sensitivity for Cu(2+) over other common ions in 100%
      aqueous solution. Once HL combined with Cu(2+), blue fluorescence was almost
      completely quenched and the L-Cu ensemble was formed. Moreover, the ensemble
      showed high specificity for S(2-) based on the displacement approach, and no
      interferences were observed in the presence of other anions. Such fluorescence
      modulation behavior simulates the performance of an IMPLICATION logic gate. In
      addition, the fluorescent sensor was successfully applied to fluorescent cellular
      imaging implying potential applications in physiological and environmental
      systems. 

PMID- 24572940
TI  - Proceedings of the 25th anniversary meeting of the Society for Back Pain
      Research.

PMID- 24572941
TI  - The Society for Back Pain Research: how did it start?

PMID- 24572942
TI  - Occupational back pain: then and now.

PMID- 24572943
TI  - Mechanisms of chronicity?

PMID- 24572944
TI  - Research and the prevention of chronicity.

PMID- 24572945
TI  - What about the next 25 years?

PMID- 24572946
TI  - Back to the future: what have we learned from 25 years of research into
      intervertebral disc biology?

PMID- 24572947
TI  - Does previous physical therapy contribute to self-reported disability in chronic
      low back pain?

PMID- 24572948
TI  - Lumbar spine motion during freestyle lifting and changes in this motion with
      time.

PMID- 24572949
TI  - A prospective evaluation of both outcome and psychological status in 100 patients
      with mechanical lower back pain.

PMID- 24572950
TI  - Measurement of lumbar spinal flexion-extension kinematics from lateral
      radiographs.

PMID- 24572951
TI  - Viscoelastic properties of nucleus pulposus.

PMID- 24572952
TI  - Can maximal back muscle strength be predicted from submaximal efforts?

PMID- 24572953
TI  - Euler buckling as a model for the curvature and flexion of the human lumbar
      spine.

PMID- 24572954
TI  - The development of a functional task-oriented measure of pain behaviour in
      chronic low back pain patients.

PMID- 24572955
TI  - The 'back home' leaflet: developing a self-management leaflet for people with
      acute low back pain.

PMID- 24572956
TI  - Patients' beliefs as to the cause of their low back pain.

PMID- 24572957
TI  - A pilot study of intervertebral disc replacement.
AB  - The aim of this study was to establish whether disc replacement can restore
      function reduced by back pain.Forty-six patients deemed suitable for disc
      replacement were assessed using the Oswestry Disability Scoring system pre
      operatively and post-operatively to assess function. The surgery was carried out
      between 1990 and 1995 using the Link (R) Charite 111 prosthesis. The post
      operative assessment was carried out by postal questionnaire.The diagnosis was
      recorded as degenerative disc disease in 41 patients, contained disc prolapse in
      one, sequestrated disc in three, foraminal stenosis in one and recurrent disc in
      two patients. Two or more diagnoses were recorded in six patients. Five patients
      who had intervertebral disc replacement had undergone previous surgery.The mean
      duration of follow-up was 3 years (range 11-72 months). Of the 46 patients (17
      male and 29 female) two were converted to fusion, one was lost to follow-up and
      three were excluded because of incomplete data sets. The mean Oswestry Disability
      score improved from 52.2 pre-operatively to 33.4 at follow-up. This is
      statistically significant (p = 0.001).This small but carefully studied group
      suggests that disc replacement can improve function in patients disabled by back
      pain. The present technology does not fail immediately nor does it simply sink
      into the vertebral bodies. Interbody fusion does not occur. 

PMID- 24572958
TI  - Debate: This Society believes that in the last 25 years of back pain research we
      have failed to see the wood for the trees - Chaired by C.G. Greenough.

PMID- 24572959
TI  - Children with pain and HIV / AIDS.

PMID- 24572961
TI  - Who is taking care of the orphan?

PMID- 24572964
TI  - The energetics of semicontact 3 x 2-min amateur boxing.
AB  - The energy expenditure of amateur boxing is unknown. PURPOSE: Total metabolic
      cost (Wtot) as an aggregate of aerobic (Waer), anaerobic lactic (W[lactate]), and
      anaerobic alactic (WPCr) energy of a 3 * 2-min semicontact amateur boxing bout
      was analyzed. METHODS: Ten boxers (mean +/- SD [lower/upper 95% confidence
      intervals]) age 23.7 +/- 4.1 (20.8/26.6) y, height 180.2 +/- 7.0 (175.2/185.2)
      cm, body mass 70.6 +/- 5.7 (66.5/74.7) kg performed a semicontact bout against
      handheld pads created from previously analyzed video footage of competitive
      bouts. Net metabolic energy was calculated using respiratory gases and blood
      [lactate]. RESULTS: Waer, 526.0 +/- 57.1 (485.1/566.9) kJ, was higher (P < .001)
      than WPCr, 58.1 +/- 13.6 (48.4/67.8) kJ. W[lactate], 26.2 +/- 7.1 (21.1/31.3) kJ,
      was lower (P < .001) than Waer and WPCr. An ~70-kJ fraction of the aerobic energy
      expenditure reflects rephosphorylation of high-energy phosphates during the
      breaks between rounds, which elevated Wtot to ~680 kJ with relative contributions
      of 77% Waer, 19% WPCr, and 4% W[lactate]. CONCLUSIONS: The results indicate that
      the metabolic profile of amateur boxing is predominantly aerobic. They also
      highlight the importance of a highly developed aerobic capacity as a prerequisite
      of a high activity rate during rounds and recovery of the high-energy phosphate
      system during breaks as interrelated requirements of successful boxing.

PMID- 24572971
TI  - No association between the HLA-DQB1*0501 variant and schizophrenia in a Chinese
      population.

PMID- 24572972
TI  - Genetic etiology of schizophrenia: possible role of immunoglobulin gamma genes.
AB  - There is increasing evidence for the involvement of herpes simplex virus type 1
      and human cytomegalovirus in the cognitive impairment of patients with
      schizophrenia (SCZ). Both herpes simplex virus type 1 and human cytomegalovirus
      have evolved strategies for decreasing the efficacy of the host immune response
      and interfering with viral clearance. Immunoglobulin GM genes, genetic markers of
      IgG heavy chains located on chromosome 14, modify certain immunoevasion
      strategies of these viruses. Particular GM alleles are also associated with
      antibody responsiveness to gliadin or gluten sensitivity, an attribute reported
      to be prevalent in a significant proportion of SCZ patients. On the basis of
      these properties, I hypothesize that GM alleles are risk factors for SCZ and
      their evaluation could help genetically dissect the disease in different subsets
      and/or help unify some disparate areas of pathobiology (e.g. cognitive
      dysfunction and gluten sensitivity) affected in this disorder. 

PMID- 24572973
TI  - Infant mortality and ethnicity in an indigenous European population: novel
      evidence from the Finnish population register.
AB  - We provide the first analyses of infant mortality rates by indigenous ethnic
      group in Finland, a country that has one of the lowest relative numbers of infant
      deaths in the world. Using files from the Finnish population register, we
      identified both of the parents of children born in the period from 1975-2003
      according to ethnic affiliation, socioeconomic profile, and demographic position.
      The infant mortality rate in homogamous Finnish unions is similar to that in
      homogamous Swedish unions, which reflects a lack of social disparities between
      the two groups. Surprisingly, infants from ethnically mixed unions have markedly
      lower mortality rates, with an adjusted rate ratio of 0.81 relative to homogamous
      Swedish unions (95% CI: 0.67-0.98). Although not empirically verified, we argue
      that the lower infant mortality rate in ethnically mixed unions may be due to
      lower levels of inbreeding, and hence related to historically low intermarriage
      rates between the two ethnic groups, remote consanguinities, and restricted inter
      community gene flow. 

PMID- 24572974
TI  - Absence of antibodies against Bordetella pertussis in pregnant women and newborns
      in the state of Nuevo Leon.
AB  - AIMS: To assess placental transfer of antibodies to the child at birth and at 2
      months of age. MATERIALS AND METHODS: For the quantification of anti-PT IgG
      antibodies, we used an indirect enzyme-linked immunosorbent assay standardized by
      The National Institute of Epidemiologic Diagnosis and Reference (InDRE). Samples
      were considered negative from 0 to 48 IU/mL, indeterminate from 49 to 93 IU/mL
      and positive at >=94 IU/mL. We performed a cross-sectional assessment of anti-PT
      IgG antibody levels in the mother, umbilical cord, and child. RESULTS: There was
      a higher concentration of IgG anti-TP in the umbilical cord (4.3%) and in the
      mother (1.4%), but a total absence was observed in the child (0%). CONCLUSION:
      The vulnerability of children to Bordetella pertussis shows the need to implement
      effective immunization strategies, whether actively, in the child, or passively
      through the mother, adolescents, and adults who are in contact with the child.

PMID- 24572975
TI  - Risk behaviors related to violence and injury among school-going adolescents in
      Karnataka, Southern India.
AB  - BACKGROUND: Adolescence is a crucial stage of life. The development and practice
      of various risk behaviors predisposes the risk of getting injured and
      consequences in later life. STUDY METHODS: This cross-sectional study was
      conducted among 381 adolescents (15-19 years) studying in different schools and
      colleges of Udupi. The Youth Risk Behavior Survey (YRBS), Center for Disease
      Control (CDC) Questionnaire and the Atlanta Questionnaire and Guidelines was
      adopted for data collection. Behaviors such as poor obeying traffic rules while
      driving, violence at school premises, and suicidal thoughts of the participants
      were explored. Univariate analysis followed by multivariate logistic regression
      was done to estimate the predictors of violence-related behavior using the
      Statistical Packages for Social Sciences (SPSS) v. 20. RESULTS: In our study,
      27.03% of students (total=381) had knowledge of traffic rules in detail, where
      65% drove a motorized vehicle. Nearly 75% of students did not use a helmet or
      seatbelt while driving and 17% used a mobile phone for either talking or texting
      while driving. Considering all violence risk behaviors, 33.07% of students had at
      least and 18% had at least two violence-related risk behaviors. Nearly 21.78%
      thought of hitting somebody, 16.34% of boys and 9.5% of girls carried sharp
      objects to school, 18.81% of boys and 10.39% of girls damaged or stole other
      students' property, 18.37% bullied others in the past month at the school campus,
      and 11.32% were involved in serious fights. Out of 381 students, 114 (30.32%)
      were bullied, 10% had been slapped intentionally, and 18% of girls felt unsafe to
      go out of their home because of threat compared with 15% of boys. In total, 71
      (18.93%) students thought of suicide and 22 of them attempted it. Logistic
      regression showed that boys [odds ratio (OR): 1.72, 95% confidence interval (CI):
      1.02-2.93) and students of 16 years of age (OR: 3.02, 95% CI: 1.06-9.02) affected
      or victimized by violent activities at school (OR: 3.23, 95% CI: 1.76-5.93) and
      bullied by others (OR: 2.6, 95% CI: 1.55-4.36) were determining factors for
      violence-related behaviors after adjusting for other variables. CONCLUSION: There
      is a need to identify students at risk and for intervention addressing the risk
      factors. Further qualitative studies could provide more insight.

PMID- 24572976
TI  - Healthy eating and physical activity.

PMID- 24572977
TI  - Effect of life skills training on physical activity patterns amongst school
      adolescents in Delhi: a non-randomized interventional study.
AB  - BACKGROUND: Effect of life skills on physical activity behavior of adolescents is
      little explored. OBJECTIVE: To assess impact of life-skills training on the level
      of physical activity amongst adolescents. METHODS: A nonrandomized interventional
      study with a control group. All students studying in Class IX and XI of two
      schools in Delhi were included. Data was collected at baseline, 15 days and 3
      months after the life-skills training. Two life-skills training sessions were
      conducted for each standard following collection of baseline data. RESULTS: There
      were 180 students in the intervention and 183 students in the control group. A
      significant increase was noted in the level of light-moderate, vigorous physical
      activity, and stretching and strengthening exercises (p<0.001) in an intervention
      group over the period of 3 months following the training. The number of students
      enrolled in physical education classes also increased. CONCLUSIONS: A skills
      based approach helped to improve the level of physical activity amongst the
      school adolescents.

PMID- 24572978
TI  - Cardiovascular disease and prevention.

PMID- 24572979
TI  - Importance of dietary calcium and vitamin D in the treatment of hypercalcaemia in
      Williams-Beuren syndrome.
AB  - BACKGROUND: Williams-Beuren syndrome (WBS) is a rare genetic disorder caused by
      the deletion of 26-28 genes on chromosome 7. Fifteen percent of WBS patients
      present with hypercalcaemia during infancy, which is generally mild and resolves
      spontaneously before the age of 4 years. The mechanisms underlying the transient
      hypercalcaemia in WBS are poorly understood. CASE: We report a case of severe
      symptomatic hypercalcaemia in a patient with WBS, in which treatment with mild
      calcium restriction, hyperhydration and repeated bisphosphonate administration
      only resulted in short-lasting effects. Long-term lowering of serum calcium was
      only achieved after reducing calcium and vitamin D intake to the bare minimum.
      CONCLUSIONS: This case illustrates the potential severity of hypercalcaemia in
      WBS, and demonstrates that both the cause as well as the solution of this problem
      may be found in the intestinal absorption of calcium. We hypothesise that the
      phenotypical resemblance between WBS and transient idiopathic infantile
      hypercalcaemia can be explained by similarities in the underlying genetic defect.
      Patients suffering from transient infantile hypercalcaemia were recently
      described to have mutations in CYP24A1, the key enzyme in 1,25-dihydroxyvitamin
      D3 degradation. In the light of this new development we discuss the role of one
      of the deleted genes in WBS, Williams syndrome transcription factor (WSTF), in
      the etiology of hypercalcaemia in WBS.

PMID- 24572980
TI  - Assessment of hearing in children with type 1 diabetes mellitus.
AB  - OBJECTIVE: To evaluate auditory function in a group of Egyptian type 1 diabetic
      children. METHODS: This was a cross sectional observational study, which included
      40 patients with type 1 diabetes and 40 controls. HbA1, urinary
      albumin/creatinine ratio, and auditory assessments (including dizziness
      questionnaire, pure tone audiometry, speech audiometry, tympanometry, and auto
      acoustic cochlear emission) were completed for all patients and controls. Mann
      Whitney U-test, chi2-test and Spearman's correlation were used for statistical
      analyses. RESULTS: Assessment of pure tone audiometry revealed that the diabetics
      had a significantly higher reading in high frequency at 8000 Hz, 16,000 Hz,
      17,000 Hz, and 18,000 Hz on the right side and at 4000 Hz, 8000 Hz, 16,000 Hz,
      17,000 Hz, and 18,000 Hz on the left side. There was a significantly lower level
      in speech reception threshold, repetition of words, and masking level of
      diabetics on the left side. Evaluation of transient otoacoustic emission revealed
      that diabetics recorded significantly lower signal to noise ratio at 4000 Hz on
      the right side and at 1000, 1500, 4000, and all Hz on left side. There was
      significant lower emission amplitude in the right side of the diabetics group at
      1500 and 4000 Hz and at 1000, 1500, and 4000 Hz on the left side. Patients with
      failed otoacoustic emission were significantly higher in disease duration >10
      years. CONCLUSION: Type 1 diabetes is associated with high/extended high
      frequency hearing loss, more prominent on the left side and with longer disease
      duration.

PMID- 24572981
TI  - Chitotriosidase as a possible marker of clinically evidenced atherosclerosis in
      dyslipidemic children.
AB  - A correlation has been clearly shown between inflammation markers and subclinical
      atherosclerosis markers in the early stages of atherogenesis in subjects with
      familial hypercholesterolemia (FH). The aim of this study was to investigate
      potential inflammation markers in the diagnosis of atherosclerosis in children
      with FH. A total of 48 dyslipidemic children and 24 healthy age-matched control
      subjects were taken into study. Inflammation and macrophage activation markers
      (hsCRP, myeloperoxidase, chitotriosidase, YKL-40, TNF-alpha, IL-6, IL-18, MMP-1
      and MMP-9) and lipid parameters of all patients were measured. Carotid intima
      media thickness (cIMT) and flow-mediated dilation (FMD) levels were determined.
      Our data suggested that clinically evidenced (by cIMT and FMD levels)
      atherosclerosis starts in the early ages in hypercholesterolemic children. Higher
      cholesterol levels strongly correlated with macrophage activation markers (ChT,
      YKL-40 and myeloperoxidase). ChT and YKL-40 seem to be the more predictable
      markers of atherosclerosis even in early ages (<6 years old) than other classical
      inflammation markers such as hs-CRP, IL-6 and TNF-alpha.

PMID- 24572982
TI  - Gut hormone profiles in preterm and term infants during the first 2 months of
      life.
AB  - AIM: To investigate changes of gut hormones in term and preterm infants in the
      first 2 months after birth, as the role and relationships of gut hormones in
      premature infants has not been well elucidated. METHODS: In 29 preterm and five
      term infants, fasting serum concentrations of leptin, glucose-dependent
      insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), peptide YY
      (PYY), pancreatic polypeptide, insulin, amylin, and ghrelin were measured using a
      bead array system. RESULTS: Serum leptin concentration soon after birth showed a
      positive correlation with gestational week in all infants (r=0.623, p<0.01).
      Serum leptin level rapidly decreased in all infants. In preterm infants, serum
      GLP-1 levels at birth showed negative correlations with gestational week (r=
      0.447, p=0.02). Serum GIP, GLP-1, and PYY levels increased after birth and were
      persistently high until 10 weeks of life. CONCLUSION: Serum concentrations of
      different gut hormones changed postnatally in their specific ways in preterm
      infants.

PMID- 24572983
TI  - Relationships of gamma-glutamyltransferase and beta 2-microglobulin on high
      sensitivity C-reactive protein among Japanese elementary school children.
AB  - Recent studies reported that gamma-glutamyltransferase (GGT) and beta 2
      microglobulin (beta2M) are possible markers of cardiovascular disease in adults,
      however, their roles among children have not been fully elucidated. We have
      examined the relationships of GGT and beta2M on C-reactive protein (CRP) among
      326 healthy elementary school children. To investigate the relationships of serum
      GGT and beta2M levels on measuring of CRP, multiple regression analysis and
      analysis of covariance (ANCOVA) were performed. After being adjusted for
      confounders, body mass index, log-transformed GGT, and beta2M were significantly
      related to CRP. Independent of other risk factors, ANCOVA showed that serum
      beta2M levels were significantly associated with serum CRP (p=0.012, p for trend
      <0.001), and GGT levels had similar results (p=0.211, p for trend=0.035). These
      results suggest that serum beta2M and GGT levels are useful indicators for
      evaluating the occurrence of slight inflammation as background, which promotes
      atherosclerosis even in healthy children.

PMID- 24572984
TI  - Circulating intact parathyroid hormone is suppressed at 25-hydroxyvitamin D
      concentrations >25 nmol/L in children.
AB  - Vitamin D status is best reflected by circulating concentrations of 25
      hydroxyvitamin D2 and D3 (25-OH-D). An adequate blood concentration of total 25
      OH-D is commonly defined as that which maintains parathyroid hormone (PTH) within
      the normal range. Consensus from studies of adults with renal impairment
      indicates that 75 nmol/L of 25-OH-D maintains suppression of PTH. No similar
      consensus exists in children. We studied the correlation of PTH and 25-OH-D in
      271 patients aged 2 months to 21 years (mean 11 years) in a tertiary care
      pediatric setting. Patients with renal impairment were excluded by elevated
      creatinine concentration and chart review. PTH did not significantly correlate
      with 25-OH-D concentrations >25 nmol/L. PTH was significantly elevated in
      specimens with <25 nmol/L of 25-OH-D (p=10-17). Using PTH suppression as
      indicator, these data suggest that 25-OH-D concentrations >25 nmol/L in children
      indicate vitamin D sufficiency.

PMID- 24572985
TI  - Antidepressant, anxiolytic, and anticataleptic effects of aqueous leaf extract of
      Antiaris toxicaria Lesch. (Moraceae) in mice: possible mechanisms of actions.
AB  - Abstract Background: The leaves of Antiaris toxicaria Lesch. (Moraceae) are used
      by traditional medicine practitioners in southwest Nigeria in the management of
      epilepsy, wounds, and neurological disorders. Hence, this study was undertaken to
      investigate the effect of the aqueous leaf extract of A. toxicaria on the central
      nervous system. Methods: One hour after administration of A. toxicaria [50-300
      mg/kg orally (p.o.)], its antidepressant effect was evaluated using the forced
      swimming test (FST), anxiolytic effect using elevated plus maze (EPM) test, and
      anticataleptic effect using haloperidol-induced catalepsy, whereas its effects on
      hypnosis and motor coordination were studied using hexobarbitone-induced sleeping
      time and open-field tests, respectively, in mice. Results: Antiaris toxicaria
      (300 mg/kg) significantly increased swimming activity (36.88%) and reduced
      immobility time (38.54%). Pretreatment of mice with prazosin (an alpha1
      adrenoceptor antagonist), sulpiride (a D2 receptor antagonist), and l-NG-nitro
      arginine (nitric oxide synthase inhibitor) 15 min before A. toxicaria (300 mg/kg
      p.o.) treatment significantly prevented its antidepressant-like effect by 35.58%,
      53.30%, and 56.11%, respectively, in the FST. However, pretreatment with
      metergoline (5-HT2 receptor antagonist), and atropine (muscarinic cholinergic
      antagonist) failed to reverse this effect. Interestingly, A. toxicaria (50 mg/kg)
      significantly increased open-arm exploration in the EPM by 70.31%, which was
      reversed by 82.66% in the presence of flumazenil [3 mg/kg intraperitoneally
      (i.p.)]. Haloperidol (1 mg/kg i.p.) induced cataleptic behavior in mice, which
      was reversed by A. toxicaria (300 mg/kg) (p<0.001) treatment. Conclusions: The
      results suggest that A. toxicaria possesses an antidepressant-like effect
      involving interaction with alpha1-adrenoceptor, D2 dopamine receptor, and
      nitrergic pathway; an anxiolytic-like effect linked to the benzodiazepine system;
      and a neuroprotective effect.

PMID- 24572986
TI  - The diverse roles of the Nup93/Nic96 complex proteins - structural scaffolds of
      the nuclear pore complex with additional cellular functions.
AB  - Nuclear pore complexes mediate the transport between the cell nucleoplasm and
      cytoplasm. These 125 MDa structures are among the largest assemblies found in
      eukaryotes, built from proteins organized in distinct subcomplexes that act as
      building blocks during nuclear pore complex biogenesis. In this review, we focus
      on one of these subcomplexes, the Nup93 complex in metazoa and its yeast
      counterpart, the Nic96 complex. We discuss its essential function in nuclear pore
      complex assembly as a linker between the nuclear membrane and the central part of
      the pore and its various roles in nuclear transport processes and beyond.

PMID- 24572987
TI  - Scan statistics analysis for detection of introns in time-course tiling array
      data.
AB  - A tiling array yields a series of abundance measurements across the genome using
      evenly spaced probes. These data can be used for detecting sequences that exhibit
      a particular behavior. Scanning window statistics are often employed for testing
      each probe while accounting for local correlation and smoothing noisy
      measurements. However, window testing may yield false probe discoveries around
      the sequences and false non-discoveries within the sequences, resulting in biased
      predicted intervals. We propose to avoid this problem by stipulating that a
      sequence of interest can appear at most once within a defined region, such as a
      gene; thus, only one window statistic is considered per region. This
      substantially reduces the number of tests and hence, is potentially more
      powerful. We compare this approach to a genome-wise scan that does not require
      pre-defined search regions, but considers clumps of adjacent probe discoveries.
      Simulations show that the gene-wise search maintains the nominal FDR level, while
      the genome-wise scan yields FDR that exceeds the nominal level for low interval
      effects, and achieves slightly less power. Using arrays to map introns in yeast,
      we identified 71% of the previously published introns, detected nine previously
      undiscovered introns, and observed no false intron discoveries by either method.

PMID- 24572988
TI  - Red cell adhesion in human diseases.
AB  - PURPOSE OF REVIEW: This review discusses the unexpected role of red blood cell
      (RBC) adhesiveness in the pathophysiology of two red cell diseases, hereditary
      spherocytosis and polycythemia vera, and two 'nonerythroid' disorders, central
      retinal vein occlusion and Gaucher disease. These pathologies share common
      clinical manifestations, that is vaso-occlusion and/or thrombotic events. RECENT
      FINDINGS: Recently, the direct involvement of RBC adhesion to the vascular
      endothelium has been demonstrated in the occurrence of vaso-occlusive events, in
      particular in sickle cell disease (SCD). Several erythroid adhesion molecules and
      their ligands have been identified that belong to different molecular classes
      (integrins, Ig-like molecules, lipids...) and are activated by a variety of
      signaling pathways. Among these, the laminin receptor, Lutheran/basal cell
      adhesion molecule, which is activated by phosphorylation, appears to play a
      central role in several pathologies. SUMMARY: RBC adhesiveness might be involved
      in complications such as the vaso-occlusive crisis in SCD, thrombosis in
      polycythemia vera, splenic sequestration in hereditary spherocytosis, occlusions
      in central retinal vein occlusion and bone infarcts in Gaucher disease.
      Characterization of this pathological process at the cellular and molecular
      levels should prove useful to develop new therapeutic approaches based on the
      blockade of RBC abnormal interactions with vascular endothelium and/or
      circulating blood cells.

PMID- 24572989
TI  - Toxicity assessment of perfluorinated carboxylic acids (PFCAs) towards the
      rotifer Brachionus calyciflorus.
AB  - The effects of acute toxicity, 3-day population growth and morphological effects
      of perfluorinated carboxylic acids (PFCAs) with carbon chain lengths of 2-6 on
      the freshwater rotifer Brachionus calyciflorus were investigated. The results
      indicated that the 24-h median lethal concentration (LC50) values of
      trifluoroacetic acid (TFA), perfluoropropionic acid (PFPrA), perfluorobutanoic
      acid (PFBA), perfluopentanoic acid (PFPeA), and perfluorohexanoic acid (PFHxA)
      towards B. calyciflorus were 70, 80, 110, 130 and 140 mg L(-1), respectively. The
      acute effects of PFCAs decreased with the increase of carbon chain length. The
      parameters used to determine 3-day population growth on these compounds were the
      rate of population increase (r) and mictic ratio. With the increase of
      fluorinated carbon-chain length, the r values of TFA, PFPrA, PFBA, PFPeA and
      PFHxA decreased by 0.99%, 16.8%, 16.5%, 22.4% and 32.0%, respectively. Mictic
      ratios ranged from 0.707 to 0.953 for PFCAs with carbon chain lengths of 2-6. In
      addition, the mictic ratio, body size and egg size exposed to some PFCAs were
      higher than those of the controls. These results offer a useful method for the
      ecological risk assessment of these short chain PFCAs.

PMID- 24572991
TI  - Quasiparticle dynamics and spin-orbital texture of the SrTiO3 two-dimensional
      electron gas.
AB  - Two-dimensional electron gases (2DEGs) in SrTiO3 have become model systems for
      engineering emergent behaviour in complex transition metal oxides. Understanding
      the collective interactions that enable this, however, has thus far proved
      elusive. Here we demonstrate that angle-resolved photoemission can directly image
      the quasiparticle dynamics of the d-electron subband ladder of this complex-oxide
      2DEG. Combined with realistic tight-binding supercell calculations, we uncover
      how quantum confinement and inversion symmetry breaking collectively tune the
      delicate interplay of charge, spin, orbital and lattice degrees of freedom in
      this system. We reveal how they lead to pronounced orbital ordering, mediate an
      orbitally enhanced Rashba splitting with complex subband-dependent spin-orbital
      textures and markedly change the character of electron-phonon coupling, co
      operatively shaping the low-energy electronic structure of the 2DEG. Our results
      allow for a unified understanding of spectroscopic and transport measurements
      across different classes of SrTiO3-based 2DEGs, and yield new microscopic
      insights on their functional properties. 

PMID- 24572990
TI  - Indirect targeting of IGF receptor signaling in vivo by substrate-selective
      inhibition of PAPP-A proteolytic activity.
AB  - The insulin-like growth factor (IGF) signaling pathway is involved in certain
      human cancers, and the feasibility of directly targeting the IGF receptor has
      been actively investigated. However, recent evidence from clinical trials
      suggests that this approach can be problematic. We have developed an alternative
      strategy to indirectly inhibit the IGF signaling by targeting the
      metalloproteinase, pregnancy-associated plasma protein-A (PAPP-A). PAPP-A
      associated with the cell surface cleaves IGF binding protein-4 (IGFBP-4), when
      IGF is bound to IGFBP-4, and thereby increases IGF bioavailability for receptor
      activation in an autocrine/paracrine manner. We hypothesized that inhibition of
      PAPP-A would suppress excessive local IGF signaling in tissues where this is
      caused by increased PAPP-A proteolytic activity. To test this hypothesis, we
      developed an inhibitory monoclonal antibody, mAb 1/41, which targets a unique
      substrate-binding exosite of PAPP-A. This inhibitor selectively and specifically
      inhibits proteolytic cleavage of IGFBP-4 with an inhibitory constant (Ki) of 135
      pM. In addition, it inhibited intracellular signaling of the IGF receptor (AKT
      phosphorylation) in monolayers of A549 cells, an IGF-responsive lung cancer
      derived cell line found to express high levels of PAPP-A. We further showed that
      mAb 1/41 is effective towards PAPP-A bound to cell surfaces, and that it is
      capable of inhibiting PAPP-A activity in vivo. Using a murine xenograft model of
      A549 cells, we demonstrated that mAb 1/41 administered intraperitoneally
      significantly inhibited tumor growth. Analysis of xenograft tumor tissue
      recovered from treated mice showed penetration of mAb 1/41, reduced IGFBP-4
      proteolysis, and reduced AKT phosphorylation. Our study provides proof of concept
      that IGF signaling can be selectively reduced by targeting a regulatory
      proteinase that functions extracellularly, upstream of the IGF receptor. PAPP-A
      targeting thus represents an alternative therapeutic strategy for inhibiting IGF
      receptor signaling. 

PMID- 24572992
TI  - Interleukin-6 in inflammatory and malignant diseases of the pancreas.
AB  - Interleukin-6 is an important pro-inflammatory cytokine strongly linked to the
      most burdened exocrine pancreatic diseases including acute pancreatitis, chronic
      pancreatitis and pancreatic cancer. However, its role in all these diseases is
      versatile and not completely defined. Several studies provided accumulating
      evidence that IL-6 is mainly involved in the JAK/STAT pathway activation
      promoting acute and chronic pancreatitis disease aggravation as well as
      pancreatic cancer initiation and progression. This review will focus on recent
      studies illustrating the role of IL-6 in acute and chronic pancreatitis and
      pancreatic oncogenesis. Further, a short overview of indicated disease
      pathologies will be given and the impact of IL-6 in JAK/STAT pathway, persistent
      STAT3 activation and cancer immunotherapy will be discussed. 

PMID- 24572993
TI  - New first order Raman-active modes in few layered transition metal
      dichalcogenides.
AB  - Although the main Raman features of semiconducting transition metal
      dichalcogenides are well known for the monolayer and bulk, there are important
      differences exhibited by few layered systems which have not been fully addressed.
      WSe2 samples were synthesized and ab-initio calculations carried out. We
      calculated phonon dispersions and Raman-active modes in layered systems: WSe2,
      MoSe2, WS2 and MoS2 ranging from monolayers to five-layers and the bulk. First,
      we confirmed that as the number of layers increase, the E', E" and E2g modes
      shift to lower frequencies, and the A'1 and A1g modes shift to higher
      frequencies. Second, new high frequency first order A'1 and A1g modes appear,
      explaining recently reported experimental data for WSe2, MoSe2 and MoS2. Third,
      splitting of modes around A'1 and A1g is found which explains those observed in
      MoSe2. Finally, exterior and interior layers possess different vibrational
      frequencies. Therefore, it is now possible to precisely identify few-layered
      STMD. 

PMID- 24572994
TI  - Id1 and NF-kappaB promote the generation of CD133+ and BMI-1+ keratinocytes and
      the growth of xenograft tumors in mice.
AB  - Id1 and NF-kappaB are highly expressed in oral squamous cell carcinoma (OSCC).
      Whether they have a synergistic role in the carcinogenesis of OSCC is unclear.
      The current study was designed to demonstrate the synergy of both Id1 and NF
      kappaB in the underlying disease mechanisms of OSCC using in vitro and in vivo
      animal models. Id1 and NF-kappaB strengthened the expression of both CD133 and
      BMI-1 in OSCC cell cultures. CD133(+) and BMI-1(+) keratinocytes from OSCC
      tissues and cell cultures initiated the growth of xenograft tumors in SCID/Beige
      mice. Id1 and NF-kappaB regulate the expression of CD133 and BMI-1 in an additive
      or synergistic manner in OSCC, which is associated with the generation of naive
      and self-renewable keratinocytes and initiate the growth of xenograft tumors in
      vivo.

PMID- 24572995
TI  - A reassessment of penile sensory pathways and effects of prilocaine-lidocaine
      cream in primary premature ejaculation.
AB  - To assess the penile sensory pathway abnormalities of the patients with primary
      premature ejaculation (PPE) and effects of prilocaine-lidocaine (PLA) cream, we
      enrolled 82 PPE patients and 34 normal potent male volunteers. Somatosensory
      evoked potentials of dorsal nerve (DNSEP) and glans penis (GPSEP) were performed
      in each subject. In addition, among the 82 patients, 60 were selected and
      randomly divided into PLA and placebo subgroups, each with 30 patients. Cream was
      applied evenly on the glans penis for 10 min and washed off just before DNSEP and
      GPSEP were repeatedly measured. Mean latencies of DNSEP and GPSPE were both
      remarkably shorter in the patients than those in the normal potent men (P<0.001,
      both). Compared with the control group, the mean amplitudes of GPSEP were
      significantly greater in the patient group (P<0.001), but not considerably on the
      amplitudes of DNSEP (P=0.229). After cream application, the latencies and
      amplitudes of both DNSEP and GPSEP were significantly prolonged and reduced,
      respectively, in the PLA cream subgroup (P<0.001, all). These results showed that
      hyperexcitable ejaculatory reflex neurological factor was linked to PPE, because
      of hypersensitivity of the penile, accelerated conduction and cortical
      amplification of the genital stimuli. The PLA cream could delay sensory latency
      and decrease glans penile hyperexcitability, which may be the mechanism for PPE
      treatment.

PMID- 24572996
TI  - Penile plication for Peyronie's disease: our results with mean follow-up of 103
      months on 89 patients.
AB  - To evaluate the outcome of the long-term follow-up in patients who underwent
      corporoplasty-straightening treatment for Peyronie's disease. Between 1990 and
      2012, a total of 89 patients underwent corporoplasty-straightening surgery using
      penile plication for Peyronie's disease. We followed up on all the patients for
      the following: (a) the correction of the curvature; (b) any penile shortening;
      (c) sexual function; and (d) complications. The mean follow-up period was 103
      months. Complete correction of the curvature was obtained in 81 patients (91%).
      Shortening of the penis (1.5 to <3 cm) occurred in 20 patients (22.5%) and 79
      patients (88.7%) had good erectile function (International Index of Erectile
      Function (IIEF) 5> 21). The most frequent complication was the sensitivity
      reduction of the glans in eight patients (8.9%), which was resolved within about
      a year after surgery (mean 11 months) and the shortening of the penis in 20
      patients (22.5%), which, however, did not result in problems during sexual
      intercourse. Corporoplasty using penile straightening plication is a safe
      procedure whose results are maintained for even many years after surgery. It is a
      procedure that can be applied to any type of curvature. Any reduction in the
      length of the penis, as a result of the surgery procedure, does not lead to
      difficulties in sexual intercourse. 

PMID- 24572998
TI  - Treatment of Kawasaki disease with anti-TNF antibodies.

PMID- 24572999
TI  - Visible light photoredox-catalysed intermolecular radical addition of alpha-halo
      amides to olefins.
AB  - We present alpha-chloro amides as a new class of alpha-acetyl radical precursors,
      which undergo a tin-free, photoredox-catalysed intermolecular alpha-alkylation
      with various olefins exclusively in an anti-Markovnikov fashion. The reaction
      represents a reductive atom transfer radical addition (ATRA) and provides a
      series of alkylated amides in good yields. 

PMID- 24572997
TI  - Infliximab for intensification of primary therapy for Kawasaki disease: a phase 3
      randomised, double-blind, placebo-controlled trial.
AB  - BACKGROUND: Kawasaki disease, the most common cause of acquired heart disease in
      developed countries, is a self-limited vasculitis that is treated with high doses
      of intravenous immunoglobulin. Resistance to intravenous immunoglobulin in
      Kawasaki disease increases the risk of coronary artery aneurysms. We assessed
      whether the addition of infliximab to standard therapy (intravenous
      immunoglobulin and aspirin) in acute Kawasaki disease reduces the rate of
      treatment resistance. METHODS: We undertook a phase 3, randomised, double-blind,
      placebo-controlled trial in two children's hospitals in the USA to assess the
      addition of infliximab (5 mg per kg) to standard therapy. Eligible participants
      were children aged 4 weeks-17 years who had a fever (temperature >=38.0 degrees
      C) for 3-10 days and met American Heart Association criteria for Kawasaki
      disease. Participants were randomly allocated in 1:1 ratio to two treatment
      groups: infliximab 5 mg/kg at 1 mg/mL intravenously over 2 h or placebo (normal
      saline 5 mL/kg, administered intravenously). Randomisation was based on a
      randomly permuted block design (block sizes 2 and 4), stratified by age, sex, and
      centre. Patients, treating physicians and staff, study team members, and
      echocardiographers were all masked to treament assignment. The primary outcome
      was the difference between the groups in treatment resistance defined as a
      temperature of 38.0 degrees C or higher at 36 h to 7 days after completion of the
      infusion of intravenous immunoglobulin. Analysis was by intention to treat. This
      trial is registered with ClinicalTrials.gov, NCT00760435. FINDINGS: 196 patients
      were enrolled and randomised: 98 to the infliximab group and 98 to placebo. One
      patient in the placebo group was withdrawn from the study because of hypotension
      before receiving treatment. Treatment resistance rate did not differ
      significantly (11 [11.2%] for infliximab and 11 [11.3%] for placebo; p=0.81).
      Compared with the placebo group, participants given infliximab had fewer days of
      fever (median 1 day for infliximab vs 2 days for placebo; p<0.0001). At week 2,
      infliximab-treated patients had greater mean reductions in erythrocyte
      sedimentation rate (p=0.009) and a two-fold greater decrease in Z score of the
      left anterior descending artery (p=0.045) than did those in the placebo group,
      but this difference was not significant at week 5. Participants in the infliximab
      group had a greater mean reduction in C-reactive protein concentration (p=0.0003)
      and in absolute neutrophil count (p=0.024) at 24 h after treatment than did those
      given placebo, but by week 2 this difference was not significant. At week 5, none
      of the laboratory values differed significantly compared with baseline. No
      significant differences were recorded between the two groups at any timepoint in
      proximal right coronary artery Z scores, age-adjusted haemoglobin values,
      duration of hospital stay, or any other laboratory markers of inflammation
      measured. No reactions to intravenous immunoglobulin infusion occurred in
      patients treated with infliximab compared with 13 (13.4%) patients given placebo
      (p<0.0001). No serious adverse events were directly attributable to infliximab
      infusion. INTERPRETATION: The addition of infliximab to primary treatment in
      acute Kawasaki disease did not reduce treatment resistance. However, it was safe
      and well tolerated and reduced fever duration, some markers of inflammation, left
      anterior descending coronary artery Z score, and intravenous immunoglobulin
      reaction rates. FUNDING: US Food and Drug Administration, Robert Wood Johnson
      Foundation, and Janssen Biotech.

PMID- 24573001
TI  - From the editor.

PMID- 24573000
TI  - Diagnosis of pigmented skin tumours in a dermatological setting: different
      aspects of the number needed to excise as a measure of efficiency.
AB  - The increasing incidence of melanoma prompts a need for efficient management of
      this patient group. In this study, we use the number needed to excise (NNE), as a
      measurement of the efficiency of diagnosing melanoma. From January 2009 to
      December 2012, postoperative records from all patients were prospectively
      registered. All excised tumours with the histopathological diagnosis of naevus,
      melanoma or seborrhoeic keratosis were included. NNE values, both excluding and
      including seborrhoeic keratosis, changes over time, as well as patient- and
      tumour-related factors influencing NNE were determined. In total, 1,717 cases
      were included. The overall NNE value was 6.5, and the value fell significantly (r
      = 0.959, p = 0.041) during the 4-year study period from 8.2 to 4.8. NNE values
      decreased with increasing patient age to 1.8 in patients >= 80 years of age. The
      overall NNE value including seborrhoeic keratosis was 6.8. 

PMID- 24573002
TI  - Narcotics for benign pain? Never!

PMID- 24573003
TI  - Pain, psychological status, and functional recovery in chronic pain patients on
      daily opioids: a case comparison.
AB  - Long-term opioid therapy for chronic benign pain remains controversial. Most
      studies on the effectiveness of such regimens have been case series or case
      comparisons and very few randomized placebo-controlled studies are available.
      Overall, this research has produced mixed results. The current study sought to
      further explore issues regarding the effectiveness of opioids for chronic pain
      and to examine the use of adjunctive medications in these patients. A random
      sample of 100 patients taking daily opioids (Opioid) and 100 taking no opioids
      (Non-opioid) at evaluation were selected from the patient population of a
      tertiary care multidisciplinary pain program. Statistical analyses revealed that
      the two groups did not differ regarding pain type, duration, location, or
      surgical history. Non-Caucasians were less likely to be taking opioids than
      Caucasians (p<0.05). Relative to the Non-opioid group, Opioid patients were less
      frequently taking non-steroidal anti-inflammatories (p<0.01) and were more often
      taking anxiolytics (p<0.05) and muscle relaxants (p<0.01). Opioid patients
      reported higher (p<0.05) current pain and more frequently (p<0.05) reported
      current or past clinical depression or anxiety. No other significant differences
      were noted on measures of pain, psychological status, or functioning. Statistical
      removal of the effects of pain differences did not alter the pattern of results
      for psychological and functional measures. Although the study design employed did
      not allow determination of causality, it is consistent with previous work which
      has failed to reveal any advantage to use of daily opioids in the chronic pain
      population with regard to analgesia, decreased adjunctive medication use, or
      functional recovery. Well-designed, prospective, randomized studies are needed,
      but the current results suggest continued caution in the use of daily opioids
      until such studies become available. 

PMID- 24573004
TI  - Evaluation and management of back pain: preventing disability.
AB  - Musculoskeletal pain has become a major public health problem with medical,
      occupational and socioeconomic implications. This paper reviews the problem of
      musculoskeletal back pain, impairment and implications for disability with
      specific reference to recent meta-analyses such as those performed by the Agency
      for Health Care Policy and Research (1994) and the IASP Task Force on Pain in the
      Workplace (1995). Data from these and other studies are consistent with our
      clinical findings suggesting that most cases of low back pain are idiopathic with
      an obscure etiology. As such they should be classified as non-specific low back
      pain (NSLBP) or back pain of undetermined etiology. The authors suggest that
      despite a paucity of objective findings many patients receive diagnoses difficult
      to justify and extensive diagnostic evaluation, some of which may be
      inappropriate and contribute to iatrogenic disability. Principles for appropriate
      diagnostic and therapeutic management are discussed with specific attention to
      risk factors likely to adversely influence treatment outcome and contribute to
      unnecessary disability. 

PMID- 24573005
TI  - Neuromuscular and somatic problems of post-acute brain injury patients.
AB  - Information regarding traumatic brain injury sequelae in a sample of 503
      traumatic brain injury patients was obtained using the Neurobehavioral
      Functioning Inventory (NFI). Data revealed that motor dysfunction was more
      frequently reported than somatic difficulties. Analyses of variance indicated
      that unemployed patients experienced significantly more motor problems than
      patients working 40 or more hours per week. No differences in the incidence of
      somatic complaints, headaches, or muscular pain were found between employed and
      unemployed patients. Data suggests that long-term, interdisciplinary
      rehabilitation may be cost effective, especially when viewed in the context of
      successful employment. 

PMID- 24573006
TI  - Management guidelines for participation in collision activities with congenital,
      developmental, or post-injury lesions involving the cervical spine.
AB  - Conditions involving the cervical spine in the athlete requiring management
      decisions are numerous. The purpose of this paper is to present appropriate
      guidelines for return to collision activities in those with congenital,
      developmental, or post-injury lesions. Collision activities include boxing,
      football, ice hockey, lacrosse, rugby and wrestling. Information compiled from
      over 1200 cervical spine lesions documented by the National Football Head and
      Neck Injury Registry, an extensive literature review, as well as an understanding
      of injury mechanisms have resulted in reasonable management guidelines. Each of
      the congenital, developmental and post-traumatic conditions presented are
      identified as either no contraindication, relative contraindication, or an
      absolute contraindication on the basis of a variety of parameters. Conditions
      involved in the discussion include: odontoid anomalies, spina bifida occulta,
      atlanto-occipital fusion, K1ippel-Feil syndrome, cervical canal stenosis, spear
      tackler's spine; and traumatic conditions of the upper, middle and lower cervical
      spine including ligamentous injuries and fractures, intervertebral disc injuries
      and post-cervical spine fusion. It should be emphasized that the proposed
      guidelines should be used in the decision making process and in conjunction with
      other such factors as age, experience, ability of the individual, level of
      participation, position played, as well as the attitude and desires of the
      athlete and his parents, where applicable following an informed discussion of the
      problem with particular regard to potential risk. 

PMID- 24573007
TI  - The use of opioids in treatment of chronic pain: an examination of the ongoing
      controversy.

PMID- 24573008
TI  - Chronic whiplash associated disorder treated with home cervical traction.
AB  - The subject of this case report is a 43-year-old woman who suffered a whiplash
      associated disorder as a result of a motor vehicle accident (15 October, 1993).
      Within several hours she developed neck pain and the next day head pain, earache
      and a sore throat which became chronic, creating significant disability and a
      poor quality of life. A variety of diagnostic tests, medications and physical
      therapy from October 1993 to December 1994 were unsuccessful in determining a
      cause or relieving her complaint. In January 1995, the patient was a very angry,
      frustrated woman, reluctant to trust another trial of physical therapy. After
      observing her cervical motion, a home program of cervical traction and exercise
      was implemented. She was followed by the same physical therapist for 19 months
      (21 visits). This systematic, consistent and clearly defined program allowed her
      to gain control of her condition. The result of this treatment may benefit other
      patients suffering chronic whiplash associated disorder. 

PMID- 24573009
TI  - Why persevere?
AB  - As you have seen, this issue of the Journal has a particular focus on chronic
      pain. As the issue of how to assess the impact of chronic pain from one
      individual to another continues to be one of uncertainty and controversy, we
      present this commentary to you to emphasize the many factors involved in the
      assessment of pain, including the psychological and emotional factors. This
      commentary peers into the perseverance factor of those suffering from disabling
      pain and disease. It is presented simply as food for thought. To what extent we,
      as clinicians, want to consider factors such as this, is left up to our own
      thinking and background. 

PMID- 24573010
TI  - Hand holding: a patient's perspective.

PMID- 24573012
TI  - Current views of haemolytic streptococcal pathogenesis.
AB  - PURPOSE OF REVIEW: Increasing disease caused by beta-haemolytic streptococci
      indicates the need for improved understanding of pathogenesis. RECENT FINDINGS:
      Streptococcus pyogenes, or group A Streptococcus (GAS), causes significant
      disease worldwide. The closely related Streptococcus dysgalactiae subspecies
      equisimilis (SDSE) is increasingly recognized as causing a similar disease
      spectrum. Whole-genome sequencing applied to the study of outbreaks may reveal
      factors that contribute to pathogenesis and changes in epidemiology. The role of
      quorum sensing in biofilm formation, and interspecies communication with other
      streptococci, is discussed. GAS has evolved multiple mechanisms to evade the
      humoral arm of innate immunity, including complement, which is well known in
      protecting the host from bacteria, and the coagulation-fibrinolytic system, which
      is increasingly recognized as an innate immune effector. SUMMARY: Molecular
      biology has enhanced our understanding of the intricate balance of host-pathogen
      interactions that result in clearance or establishment of invasive streptococcal
      infection. Although the skin and oropharynx remain the usual ecological niche of
      GAS and SDSE, occasionally the bacteria find themselves within deeper tissues and
      blood. Recent research has armed us with better knowledge of bacterial
      adaptations to this alternative environment. However, the challenge is to
      translate this knowledge into clinical practice, through the development of novel
      therapeutic options and ultimately a vaccine against GAS.

PMID- 24573013
TI  - Antimicrobial-resistant Gram-negative bacteria in febrile neutropenic patients
      with cancer: current epidemiology and clinical impact.
AB  - PURPOSE OF REVIEW: In the recent years, several studies involving cancer patients
      have demonstrated a clear trend in the epidemiology of bacterial infections
      showing a shift in the prevalence from Gram-positive to Gram-negative bacteria
      and the extensive emergence of antimicrobial-resistant strains among Gram
      negatives isolated from the blood. The aim of this systematic review was to
      examine the recent trends in epidemiology and antimicrobial resistance in Gram
      negatives recovered from neutropenic cancer patients, with particular emphasis on
      the impact of antimicrobial resistance on the clinical outcome of severe
      infections caused by such microorganisms. RECENT FINDINGS: Overall, from 2007 to
      date, the rate of Gram-negative bacteria recovery ranged from 24.7 to 75.8% (mean
      51.3%) in cancer patient cohorts. Escherichia coli represented the most common
      species (mean frequency of isolation 32.1%) among the Gram-negatives, followed by
      Pseudomonas aeruginosa (mean frequency of isolation 20.1%). An increasing
      frequency of Acinetobacter spp. and Stenotrophomonas maltophilia was also
      reported. Increased rates of multidrug-resistant Gram-negative strains have been
      highlighted among Enterobacteriaceae and nonfermenting Gram-negative rods,
      despite discontinuation of fluoroquinolone-based antibacterial prophylaxis for
      neutropenic patients. In addition, antimicrobial resistance and/or the inadequacy
      of empirical antibiotic treatment have been frequently linked to a worse outcome
      in cancer patients with bloodstream infections caused by Gram-negative isolates.
      SUMMARY: Sound knowledge of the local distribution of pathogens and their
      susceptibility patterns and prompt initiation of effective antimicrobial
      treatment for severe infections caused by Gram-negative bacteria are essential in
      cancer patients.

PMID- 24573014
TI  - Impact of the integrated guidance on the care of familial hypercholesterolaemia.

PMID- 24573015
TI  - Predictors of symptomatic and asymptomatic intracranial atherosclerosis: what is
      different and why?
AB  - AIM: The prognoses of symptomatic and asymptomatic intracranial atherosclerotic
      stenosis(ICAS) differ. Understanding the underlying pathomechanisms and
      predictors of progression or regression may help to clarify the differences. We
      herein attempted to compare the course and predictors of symptomatic ICAS to
      those of coexisting asymptomatic ICAS. METHODS: This was a post-hoc analysis of
      the 'Trials of Cilostazol in Symptomatic intracranial arterial stenosis-2(TOSS
      2)' study, which recruited patients with acute symptomatic ICAS receiving
      intensive medical treatment. Changes in the status of ICAS were classified as
      being indicative of regression, progression or no changes. Univariate and
      multivariate ordinal regression analyses were performed to identify predictors of
      symptomatic and asymptomatic ICAS based on clinical, laboratory and radiologic
      data. RESULTS: Of the 409 patients, symptomatic ICAS demonstrated regression in
      110(27%) cases and progression in 52(13%) cases. Among these patients, 250(61.1%)
      had asymptomatic ICAS, which regressed in 38(15%) cases and progressed in 16(6%)
      cases. Severe baseline stenosis, a high high-density lipoprotein(HDL) cholesterol
      level and the use of cilostazol were found to be independently associated with a
      favorable course of symptomatic ICAS(p<0.001, p=0.005 and p=0.038, respectively).
      Regarding asymptomatic ICAS, severe stenosis, the use of angiotensin receptor
      antagonists and a low fasting glucose level were associated with a favorable
      course(p<0.001, p=0.011 and p=0.007, respectively). CONCLUSIONS: Changes in
      atherosclerosis are more dynamic in patients with symptomatic ICAS, and the
      predictors of symptomatic and asymptomatic ICAS differ. In this study, changes in
      the status of symptomatic ICAS were associated with the level of HDL cholesterol,
      which is known to affect the regression of atherosclerosis and vascular
      remodeling.

PMID- 24573016
TI  - Reference interval for the apolipoprotein B-48 concentration in healthy Japanese
      individuals.
AB  - AIM: Small intestine-derived chylomicrons and chylomicron remnants, which are
      predominant in patients with postprandial hypertriglyceridemia, chylomicron
      syndrome and/or familial dyslipidemia, carry one molecule of apolipoprotein B
      48(apo B-48) per lipoprotein particle. We investigated the reference interval for
      the apo B-48 concentration. METHODS: We studied 516 individuals who provided
      written informed consent and confirmed that they were not taking any medications.
      BMI, waist circumference, blood pressure and the fasting serum concentrations of
      LDL-C, triglyceride(TG), HDL-C and apo B-48 were measured. The Apo B-48
      concentrations were compared according to sex, a pre- or postmenopausal status,
      dyslipidemia(LDL-C >=140 mg/dL, TG >=150 mg/dL, HDL-C <40 mg/dL), metabolic
      syndrome(MetS) and the number of risk factors. RESULTS: The fasting apo B-48
      concentrations(mean+/-SD) were significantly higher in men than in women(3.8+/
      3.3 MUg/mL vs 2.4+/-1.9 MUg/mL, p<0.001), subjects with a BMI of >=25 kg/m(2)
      versus a BMI of <25 kg/m(2) (4.4+/-3.7 MUg/mL vs 2.8+/-2.4 MUg/mL, p<0.001) and
      those with versus without MetS(6.5+/-4.3 MUg/mL vs 3.0+/-2.6 MUg/mL, p<0.001).
      High apo B-48 concentrations were also observed in correlation with the number of
      risk factors for the MetS. The upper reference limit of apo B-48 was estimated to
      be 5.7 MUg/mL among the 332 patients with normolipidemia, excluding those
      exhibiting a mean value above +/-2.58 standard deviations(SDs), as the mean and
      range of mean +/-1.96 SD were calculated to be 2.04 MUg/mL(reference value) and
      0.74 to 5.65 MUg/mL(reference interval), respectively. CONCLUSIONS: Based on our
      study of normolipidemic patients, the upper reference limit for the fasting apo B
      48 concentration is estimated to be 5.7 MUg/mL.

PMID- 24573017
TI  - Associations between the CDKN2A/B, ADTRP and PDGFD polymorphisms and the
      development of coronary atherosclerosis in Japanese patients.
AB  - AIM: Genome-wide association studies have identified a series of susceptibility
      loci for coronary artery disease(CAD). The present study attempted to replicate
      the results for eight of these loci, CDKN2A/B(rs1333049), ADTRP(rs6903956),
      PDGFD(rs974819), TCF21(rs12190287), COL4A1-A2(rs4773144), HHIPL1(rs2895811),
      ADAMTS7(rs4380028) and UBE2Z(rs46522), in patients with pathologically defined
      atherosclerosis of the coronary arteries. METHODS: Autopsy cases of elderly
      Japanese subjects were enrolled in the JG-SNP study(n=1,536). Polymorphisms were
      genotyped, and their associations with the coronary stenosis index(CSI) and
      incidence of pathological myocardial infraction(MI) were investigated. The
      potential combinatorial effects of the susceptibility loci were also assessed.
      RESULTS: Among the eight loci tested, three exhibited signs of positive
      associations. CDKN2A/B showed the most robust associations with CSI and
      MI(p=0.007 and OR=1.843, 95% CI 1.293-2.629, p=0.001, for CC+CG vs. GG). In
      addition, ADTRP demonstrated associations with CSI and MI, although the risk
      allele was opposite from that observed in the original report(p=0.008 and
      OR=1.652, 95% CI 1.027-2.656, p=0.038 for GG vs. AA+AG). Meanwhile, PDGFD
      displayed a suggestive association with CSI in women, but not men(p=0.023).
      CDKN2A/B and ADTRP were also found to be significantly associated with the
      severity of the CSI in a case-control setting. The cumulative risk allele
      counting of CDKN2A/B, ADTRP and PDGFD indicated an increased number of risk
      alleles to be associated with a higher CSI(p=4.61E-05). CONCLUSIONS: The present
      study confirmed the association between CDKN2A/B and CAD and identified a
      different associated risk allele of ADTRP. PDGFD was found to exhibit a gender
      specific association with CAD. The combination of multiple risk alleles may be
      associated with a higher risk of CAD.

PMID- 24573018
TI  - Role of Kruppel-like factor 4 and its binding proteins in vascular disease.
AB  - Kruppel-like factor 4(KLF4) is a zinc-finger transcription factor that plays a
      key role in cellular differentiation and proliferation during normal development
      and in various diseases, such as cancer. The results of recent studies have
      revealed that KLF4 is expressed in multiple vascular cell types, including
      phenotypically modulated smooth muscle cells(SMCs), endothelial cells and
      monocytes/macrophages and contributes to the progression of vascular diseases by
      activating or repressing the transcription of multiple genes via its associations
      with a variety of partner proteins. For example, KLF4 decreases the expression of
      markers of SMC differentiation by interacting with serum response factor, ELK1
      and histone deacetylases. KLF4 also suppresses SMC proliferation by associating
      with p53. In addition, KLF4 enhances arterial medial calcification in concert
      with RUNX2. Furthermore, endothelial KLF4 represses arterial inflammation by
      binding to nuclear factor-kappaB. This article summarizes the role of KLF4 in
      vascular disease with a particular focus on in vivo studies and reviews recent
      progress in our understanding of the regulatory mechanisms involved in KLF4-
      mediated gene transcription.

PMID- 24573020
TI  - Au nanoparticles on citrate-functionalized graphene nanosheets with a high
      peroxidase-like performance.
AB  - In this paper, Au nanoparticles (AuNPs) have been homogeneously deposited on
      citrate-functionalized graphene nanosheets (Cit-GNs) by a simple one-pot reducing
      method. The morphology and composition of the thus-prepared AuNPs/Cit-GNs were
      characterized by transmission electron microscopy (TEM), high resolution TEM,
      energy dispersive X-ray spectroscopy and X-ray photoelectron spectroscopy. The
      results showed that the AuNPs with a uniform size are well dispersed on the
      surface of the Cit-GNs. Significantly, the as-prepared AuNPs/Cit-GNs possess
      intrinsic peroxidase-like activity, which can catalyze the oxidation of the
      peroxidase substrate 3,3,5,5-tetramethylbenzidine (TMB) by hydrogen peroxide
      (H2O2) to develop a blue color in aqueous solution. The catalysis was in
      accordance with Michaelis-Menten kinetics and the AuNPs/Cit-GNs showed a strong
      affinity for both H2O2 and TMB. Moreover, by comparing with Cit-AuNPs, AuNPs/GNs
      and AuNPs/PVP-GNs, the AuNPs/Cit-GNs composite exhibits a higher catalytic
      ability with a lower Michaelis constant (Km) value, suggesting that the GNs with
      a large surface area and the citrate ions with more carboxyl groups around the
      AuNPs can greatly enhance the peroxidase-like activity of AuNPs/Cit-GNs. Taking
      the advantages of the high catalytic activity, the good stability and the low
      cost, the novel AuNPs/Cit-GNs represent a promising candidate as an enzyme mimic
      and may find a wide range of new applications in biochemistry and biotechnology. 

PMID- 24573021
TI  - Musculoskeletal Complications of CancerA Survey of 50 Patients.
AB  - A variety of complications associated with cancer may adversely affect the spine
      and musculoskeletal system, resulting in physical impairment, pain, or both.
      Dysfunction may arise because of tissue injury at the primary site of disease;
      from metastatic lesions and paraneoplastic syndromes; or as the result of
      treatment and bed rest. This study evaluated 50 patients seen in consultation by
      the Rehabilitation Service at Memorial Sloan-Kettering Cancer Center (28
      retrospective, 22 prospective). Patients were evaluated for functional problems
      resulting from their disease or therapy. Patients were noted to have an average
      of 1.74 physical impairments. Thirteen (26%) patients had only one identifiable
      problem adversely affecting function. Fifty-four percent of patients were found
      to have two physical impairments. Ten patients (20%) had three or more such
      abnormalities. The mean Karnofsky score, a measure commonly used in assessing
      cancer patient function, at initial evaluation was 46.6 (standard deviation (SD)
      12.05). The most frequently encountered problem limiting function was
      deconditioning (56%); 36% of patients had central nervous system dysfunction; 28%
      had peripheral neurologic disease; 22% of patients were found to have bone
      metastasis. Additionally, pain was present in 44% of all patients. These results
      suggest that it is common for cancer patients who are referred for physiatric
      evaluation to have more than one functional problem, and that deconditioning,
      neurological, and skeletal abnormalities are common causes of impairment in
      cancer patients.Cancer is a significant cause of morbidity and mortality in the
      United States.1 It is a disease process which is inherently destructive, both at
      the primary site as well as areas to which it may spread. Additionally, remote
      effects of cancer, such as paraneoplastic syndromes, may result in further
      compromise of the patient. Antineoplastic therapies such as chemotherapy,
      radiotherapy, and surgery are also potentially injurious to native tissues and
      organ systems. The deleterious effects of these direct and indirect consequences
      of cancer, whether affecting the musculoskeletal, nervous, cardiovascular, or
      pulmonary systems, may result in functional impairment and disability. Therefore,
      it is not surprising to find a high prevalence of disabilities among cancer
      patients.2,3Significant functional impairment has been noted by previous
      authors.2,3 A variety of organ systems may be either primarily or secondarily
      involved, including the spine and musculoskeletal systems. These authors have
      demonstrated a high prevalence of functional deficits in cancer patients.
      Additionally, they noted that the majority of cancer patients with disabilities
      can be successfully treated by physical medicine intervention. The principal
      impediments preventing patients from obtaining optimal rehabilitation, as
      determined by these authors were: primary care physicians' inability to recognize
      functional impairment; and a lack of understanding by these same physicians in
      rehabilitation principles.2The scope of musculoskeletal and neurological
      impairments, as well as the number of functionally compromising problems faced by
      the individual patient is less well known. The object of this survey was to
      evaluate a series of cancer patients, seen in consultation by a rehabilitation
      medicine service, for musculoskeletal, neurologic, and other relevant
      impairments. 

PMID- 24573022
TI  - Pharmacotherapy of Cancer PainA Practical Guide.
AB  - Chronic pain is experienced by approximately one-third of all cancer patients and
      as many as 70 to 90% of those with advanced disease.1 Although established
      pharmacotherapeutic strategies have been demonstrated to benefit most patients,
      undertreatment remains common.1 This unacceptable situation must be remedied;
      relief of cancer pain is an ethical imperative and it is incumbent upon
      clinicians to maximize the knowledge, skill, and diligence needed to attend to
      this task.2Analgesic pharmacotherapy is the mainstay approach in the management
      of cancer pain.3,4 Optimal therapy depends on an understanding of the clinical
      pharmacology of analgesic drugs and comprehensive assessment of the pain, medical
      condition, and psychosocial status of the patient. Through a process of repeated
      evaluations, therapy with opioid, nonopioid, and adjuvant analgesics is
      individualized to achieve and maintain a favorable balance between pain relief
      and adverse effects.An expert committee convened by the Cancer Unit of the World
      Health Organization has proposed a useful approach to drug selection for cancer
      pain, which has become known as the "analgesic ladder" (Fig. 1).3 When combined
      with appropriate dosing guidelines, this approach is capable of providing
      adequate relief to 70 to 90% of patients.5-9 Emphasizing that the intensity of
      pain, rather than its specific etiology, should be the prime consideration in
      analgesic selection, the approach advocates the following three basic steps:Step
      1. Patients with mild to moderate cancer-related pain should be treated with a
      nonopioid analgesic, which should be combined with an adjuvant analgesic if a
      specific indication for one exists.Step 2. Patients who are relatively
      nontolerant and present with moderate to severe pain, or who tail to achieve
      adequate relief after a trial of a nonopioid analgesic, should be treated with a
      socalled "weak" opioid; this drug is typically combined with a nonopioid and may
      be coadministered with an adjuvant analgesic or other adjuvant drug, if there is
      an indication for one.Step 3. Patients who present with severe pain, or fail to
      achieve adequate relief following appropriate administration of drugs on the
      second rung of the analgesic ladder, should receive a so-called strong opioid,
      which may be combined with a nonopioid analgesic or an adjuvant drug as
      indicated. 

PMID- 24573023
TI  - The management of pathologic fractures.
AB  - This article outlines the principles of pathologic fracture management and
      highlights the clinical features that predict impending fracture so that the
      nonsurgeon can recognize how to integrate orthopedic management into the overall
      treatment plan for patients with metastatic disease to bone.With the possible
      exception of carcinoma of the breast, there is little evidence that any treatment
      increases survival of patients with metastatic carcinoma. However, advances in
      chemotherapy, radiation therapy, and surgery have undoubtedly increased the
      quality of life in these patients and has kept them active for longer periods of
      time. Judicious surgical and physiatric management is needed to optimize care. 

PMID- 24573024
TI  - Evaluation of Neoplastic Involvement of Brachial and Lumbosacral PlexusImaging
      Aspects.
AB  - Traditionally, the regions of brachial and lumbosacral plexi have been difficult
      to evaluate, both by physical examination and conventional radiography.
      Presenting symptoms of plexus involvement may include pain, paresthesia, focal
      weakness, sensory deficits, and muscle atrophy. The symptomatology as well as
      electrodiagnostic studies are nonspecific and many conditions, such as mechanical
      compromise of the pathway by a benign process, inflammation, and infiltration by
      a neoplasm originating or metastatic to the region of plexi share similar
      features and cannot be differentiated. A general term "brachial or lumbosacral
      plexopathy" is universally used, to describe a variety of clinical syndromes,
      including tumor infiltration, neuritis, postsurgical, and postradiation changes
      as well as idiopathic conditions. Significant progress in detection and
      assessment of the extent of plexus disease has been made after introduction of
      computed tomography (CT). Further anatomical detail and tissue characteristics
      have been provided by magnetic resonance imaging (MRI). However, in spite of
      valuable contribution from both imaging methods, the plexi frequently present a
      challenging problem for a clinician as well as for a radiologist. 

PMID- 24573025
TI  - Evaluation of back pain caused by epidural neoplasm.
AB  - Back pain is a common symptom in the cancer population. For some patients, the
      complaint reflects a process independent of the underlying disease, such as
      myofascial pain, discogenic disease, or osteoporosis. Many patients, however,
      experience pain as the first indication of a spinal neoplasm, and this
      possibility increases the diagnostic challenge. This article discusses the
      presentation, evaluation, and treatment of spinal epidural neoplasm in patients
      with cancer.Symptomatic epidural neoplasm occurs in approximately 5 to 10% of
      patients with metastatic cancer.1-4 Without effective treatment, the tumor
      enlarges within the closed intraspinal space and ultimately damages the spinal
      cord or nerve roots, either through direct compression or interruption of local
      blood supply. The consequences-weakness, sensory loss, and sphincteric
      dysfunction-often have a devastating impact on the patient's ability to cope with
      the physical, psychosocial, and financial burdens of the disease and its
      treatment.The prognosis for continued ambulation following presentation of
      epidural disease (ED) is influenced by numerous factors, among which are the
      radiosensitivity of the neoplasm, location of the lesion, extent of myelographic
      block, and tempo of neurological dysfunction.5-15 From the clinical perspective,
      the most salient factor is the degree of neurological impairment at the onset of
      treatment:3,5,10,14-18 Ambulation following treatment is retained by
      approximately 75% of patients who are ambulatory at the time therapy is given; 30
      to 50% regain the ability to walk if treatment is given when the patient is
      severely paretic but not plegic, and only 10% of patients who begin treatment
      while paraplegic subsequently walk.These data suggest that prevention of
      neurological compromise is possible if ED can be identified and treated early,
      before ambulation is lost. Early treatment, in turn, can only be accomplished if
      clinicians are able to recognize the population at risk through knowledge of
      those clinical indicators-symptoms or signs-that suggest the existence of ED
      before it declares itself through progressive paraparesis.Back pain is the most
      important of these clinical indicators, since pain is the first symptom in up to
      95% of cancer patients who develop ED (Table 1) and often precedes the
      development of neurological deficits by many weeks or months.1,5,13,19,20 The
      discovery and treatment of ED when back pain is the only symptom would yield
      great improvements in the overall prognosis of this population. This observation
      has been the impetus for the development of algorithms that guide the evaluation
      of cancer patients with back pain,13,14,21,22 as described below. 

PMID- 24573026
TI  - Overview of physiatric approaches to cancer pain.
AB  - The role of the rehabilitation team in the management of the cancer patient with
      pain is not well understood by either oncologists or physiatrists. Readily
      available analgesic interventions at the rehabilitationist's disposal may be
      easily employed in this population as part of a multi modality and
      interdisciplinary approach to pain. This article describes the role of the
      rehabilitation team and highlights techniques which are appropriate for cancer
      pain management. Benefits realized in addition to analgesia from physiatric
      intervention are also described.Cancer, in all its varieties, is inherently
      destructive and thereby, a potentially disabling process.1,2 Typical examples of
      the deleterious physical consequences associated with cancer include primary and
      metastatic disease of the bone and brain, epidural spinal cord compression, and
      invasion or compression of nerves by malignant spread.Options available for the
      treatment of cancer, including radical surgery, cytotoxic chemotherapy, and
      radiotherapy, administered individually or in combination, are also noxious to
      native tissues. Therefore, antineoplastic therapies may also lead to, or
      exacerbate, physical impairments. Examples include surgical amputation of a limb,
      chemotherapy induced peripheral neuropathy, and radiation osteonecrosis.Pain is
      one of the most common causes of disability in the cancer population.3,4 Thirty
      to 50% of all cancer patients suffer pain, and 70 to 90% of terminal patients
      have pain. Pain contributing to functional impairment has been noted in 44% of
      patients seen on a cancer rehabilitation service.5 The World Health Organization
      has developed clear guidelines for the assessment and recommended treatment of
      cancer pain.6 Pharmacologic and anesthetic interventions, as well as ablative and
      electro-stimulatory neurosurgical procedures, provide significant pain relief in
      the majority of cancer patients.7 These techniques, employed by a cogent
      multidisciplinary team including supportive and palliative care specialists,
      psychiatric liaison, and rehabilitation professionals may be the most efficacious
      approach in optimizing pain relief for this population.8-11This article will
      review options available to the physiatrist for the treatment of cancer pain and
      related disabilities. 

PMID- 24573027
TI  - Physiatric evaluation of the cancer patient.
AB  - As time goes on, so do the advancements in medical treatment. Today we are faced
      with a population of cancer patients living longer and developing unique problems
      as a consequence of both treatment and progression of disease. The physiatrist is
      in a unique position to enhance independence and quality of life of cancer
      patients. Often this is simply a matter of applying well-established physiatric
      principles to a unique population. However, few physiatrists in clinical practice
      have the opportunity to treat large numbers of cancer patients, especially in an
      acute care setting. Experience is key for optimal physiatric management of the
      cancer patient. The purpose of this article is to familiarize physicians and
      therapists with evaluation and subsequent application of rehabilitation
      principles to cancer patients. It is beyond the scope of this manuscript to
      discuss all the specifics of the cancer patient's rehabilitation; however,
      references are available.1-4Functional deficits in the cancer patient can arise
      from disease progression as well as its treatment. The scope of complications
      include: osseous disease, myelosuppression, multiple manifestations of
      neurological deficit, deconditioning, pain syndromes, lymphedema, gait
      abnormalities, amputation, cardiopulmonary complications, psychiatric issues, and
      others. A survey of 50 rehabilitation consultations seen over a 6-month period
      reveals the diversity of problems (see Table 1). Although a small sample, it
      correlates with our experience. Of note, many patients had more than one
      disability, as illustrated in Table 2. 

PMID- 24573028
TI  - Physiatric management of patients with metastatic disease of the spine.
AB  - The specialist in physical medicine and rehabilitation, joining with medical and
      surgical colleagues, can contribute special skills to both the diagnosis and
      management of complications related to neoplastic diseases and their treatment.
      The multifaceted team approach-lending the skills of the physiatrist and the
      physical, occupational, and speech therapists as successfully employed in the
      rehabilitation of chronic neuro-musculoskeletal disability-can with equal
      facility be utilized in the management of the cancer patient. Although in these
      instances the rehabilitative goals of caring for patients with spinal metastatic
      disease may remain essentially the same, treatment time is often telescoped by
      progressive disease requiring frequent accommodation to the staging of functional
      levels of locomotion and self-care. The direct or remote effects of the cancer
      itself; the residual effects of radical surgery, and the toxic side effects of
      chemoprophylaxis and radiotherapy, combined with a sympathetic understanding of
      the dying process, individually or collectively are challenges the physiatrist
      has to master to become a productive member of the oncology treatment team. In
      this role the physiatrist can bring to bear his or her considerable diagnostic
      expertise in the neuro-musculoskeletal clinical and electroneuromyographic
      evaluation of spinal pain and weakness syndromes as well as their treatment.
      Realistic expectations, tempered by a knowledge of the natural history of the
      specific malignancy and the presence of associated comorbidities of pain,
      asthenia, and weakness, separately and together can influence the rehabilitation
      effort to restore patients to their fullest psychological, social, vocational,
      physical, avocational, and educational potential.1. 

PMID- 24573031
TI  - From the editor.

PMID- 24573029
TI  - The role of physical therapy in patients with metastatic disease to bone.
AB  - The American Cancer Society estimates that in 1991 over seven million Americans
      were alive despite a diagnosis of cancer.1 As the medical community becomes more
      successful in prolonging the lives of cancer patients, a significant number will
      experience the resultant disability of cancer and its treatment. Those with
      advanced disease may find the quality of their lives to be profoundly
      compromised. The role of rehabilitation with the latter population is to maximize
      the patients' functional capabilities and to conserve their limited energy
      reserves. Clearly, quality of life is an overriding issue fix this population.The
      development of bony metastases is devastating for the cancer patient and presents
      a considerable challenge for the physical therapist. Approximately 50% of
      patients with breast, lung, or prostate cancer will develop bony metastases. Less
      common, though equally problematic, are bone metastases in patients with
      carcinoma of the kidney, pancreas, bladder, thyroid, and cervix.Patients with
      advanced disease present a complex clinical picture. It is imperative that the
      physical therapist consult and confer regularly with the oncologist, physiatrist,
      and/or orthopedist to remain abreast of the patient's changing clinical picture.
      Information vital to safe and effective rehabilitation includes the presence,
      location, and extent of bony metastases, involvement of bone marrow potentiating
      refractory pancytopenia, infection, and hypercalcemia secondary to prolonged
      immobility.In patients with metastatic disease to bone, it is not sufficient to
      rely solely on plain X-ray findings. Plain radiographs will not detect bone
      lesions unless a sufficient amount of matrix is destroyed (30-50% of bone matrix
      must be involved to be visualized). Bone scan results should be assessed prior to
      establishing a rehabilitation program for most cancer patients. Patients with
      advanced disease frequently present with pain, neurologic deficits, impending or
      pathologic fractures, and generalized weakness associated with prolonged
      immobility. Any new complaints of pain, or findings of progressive weakness
      should be discussed with the patient's physician in order to initiate an
      appropriate work-up. 

PMID- 24573032
TI  - Introduction.

PMID- 24573033
TI  - Adenomatous polyposis coli determines sensitivity to the EGFR tyrosine kinase
      inhibitor gefitinib in colorectal cancer cells.
AB  - Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have been
      used to treat colorectal cancer (CRC). However, resistance to EGFR-TKIs presents
      a great challenge for the treatment of CRC, and the mechanisms of resistance are
      poorly understood. The adenomatous polyposis coli (APC) protein has been known to
      contribute to the carcinogenesis of CRC. However, its role in the sensitivity of
      CRC cells to gefitinib has not been investigated. Human CRC HCT-116 (wild-type
      APC) and HT-29 (mutant APC) cells were used to investigate the effect of APC on
      the sensitivity of CRC cells to gefitinib. The MTT assay was used to measure cell
      viability after exposure to gefitinib. Cell apoptosis, migration and invasion
      were determined by flow cytometry, wound healing assay and transwell assay,
      respectively. Knockdown and overexpression of APC were performed, and activation
      of the EGFR and its downstream pathway was determined. Gefinitib inhibited
      viability, promoted apoptosis, and reduced the migration of HCT-116 and HT-29
      cells. HT-29 cells exhibited increased sensitivity to gefinitib when compared to
      HCT-116 cells. Knockdown of APC expression increased the sensitivity of HCT-16
      cells to gefitinib, accompanied by downregulation of pEGFR, p-AKT and pERK1/2. In
      contrast, overexpression of APC decreased the sensitivity of HT-29 cells to
      gefitinib, accompanied by upregulation of pEGFR, p-AKT and pERK1/2. APC plays an
      important role in the sensitivity of CRC cells to gefitinib. APC may represent a
      potential therapeutic target for the treatment of CRC. 

PMID- 24573036
TI  - Bladder cancer: seemingly similar.

PMID- 24573035
TI  - Eukaryotic expression, purification and structure/function analysis of native,
      recombinant CRISP3 from human and mouse.
AB  - While the Cysteine-Rich Secretory Proteins (CRISPs) have been broadly proposed as
      regulators of reproduction and immunity, physiological roles have yet to be
      established for individual members of this family. Past efforts to investigate
      their functions have been limited by the difficulty of purifying correctly folded
      CRISPs from bacterial expression systems, which yield low quantities of correctly
      folded protein containing the eight disulfide bonds that define the CRISP family.
      Here we report the expression and purification of native, glycosylated CRISP3
      from human and mouse, expressed in HEK 293 cells and isolated using ion exchange
      and size exclusion chromatography. Functional authenticity was verified by
      substrate-affinity, native glycosylation characteristics and quaternary structure
      (monomer in solution). Validated protein was used in comparative
      structure/function studies to characterise sites and patterns of N-glycosylation
      in CRISP3, revealing interesting inter-species differences. 

PMID- 24573037
TI  - Epigenetics: histone methyltransferase mutations promote leukaemia.

PMID- 24573038
TI  - JAK/STAT3 signaling is required for TGF-beta-induced epithelial-mesenchymal
      transition in lung cancer cells.
AB  - Epithelial-mesenchymal transition (EMT), a key step in the early stages of cancer
      metastasis, is orchestrated by several signaling pathways, including IL
      6/JAK/STAT3 and TGF-beta/Smad signaling. However, an association between the two
      signaling pathways during the EMT process is largely unknown. Here, we focused on
      lung cancer and demonstrated that TGF-beta1 induced the phosphorylation of Smad3
      (p-Smad3), upregulation of Snail, a fibroblast-like morphology, and
      downregulation of E-cadherin as well as upregulation of vimentin in lung cancer
      cell lines. SIS3 (an inhibitor of Smad3) suppressed TGF-beta1-induced activation
      of Smad3, upregulation of Snail and the EMT process. Importantly, the JAK2/STAT3
      specific inhibitor AG490 blocked Stat3 phosphorylation, resulting in attenuated
      levels of TGF-beta1-induced p-Smad3, Snail, MMP2, and Smad-mediated PAI-1
      promoter reporter gene activity in A549 and H1650 cells. Subsequently, AG490
      inhibited TGF-beta-induced cell migration and invasion. Moreover, exogenous IL-6
      treatment stimulated Stat3 activation, enhanced TGF-beta-induced expression of p
      Smad3 and Snail, aggravated the EMT process, and increased lung cancer cell
      migration and invasion induced by TGF-beta1. Our findings show that the JAK/STAT3
      pathway is required for TGF-beta-induced EMT and cancer cell migration and
      invasion via upregulation of the expression of p-Smad3 and Snail, and the IL
      6/JAK/STAT3 and TGF-beta/Smad signaling synergistically enhance EMT in lung
      carcinomas. The present study suggests a novel rationale for inhibiting cancer
      metastasis using anti-IL-6/JAK/STAT3 and anti-TGF-beta/Smad therapeutic
      strategies. 

PMID- 24573039
TI  - [Neoadjuvant short-course radiotherapy followed by chemotherapy or simultaneous
      radiochemotherapy for local unresectable rectal cancer].

PMID- 24573047
TI  - Copper-catalysed oxidative C-H/C-H coupling between olefins and simple ethers.
AB  - The first copper-catalysed oxidative alkenylation of simple ethers to construct
      allylic ethers was successfully achieved. Different substituted olefins and
      simple ethers could be cross-coupled well to generate the corresponding
      alkenylation products. Notably, open-chain ethers were also found to be efficient
      coupling partners in this reaction. This reaction is likely to proceed via a
      radical process. 

PMID- 24573040
TI  - [Gemcitabine-based or capecitabine-based chemoradiotherapy for locally advanced
      pancreatic cancer (SCALOP)].

PMID- 24573048
TI  - From the editor.

PMID- 24573050
TI  - Chronic low back pain.

PMID- 24573051
TI  - Pain management: Establishing a role for implantable technologies.
AB  - Pain due to terminal illness such as AIDS and cancer-related pain should be
      managed according to the guidelines set forth by the World Health Organization.
      These guidelines suggest a pharmacologic tailoring approach to the level and
      intensity of the patient's pain. These guidelines obey the KISS principal (keep
      it simple) suggesting the use of less potent analgesic agents before utilizing
      more potent agents. Likewise, the treatment of non-malignant pain should be based
      on the same KISS principal utilizing least costly and least invasive therapies
      either in series or in parallel until the patient's pain is well managed.
      Interventional strategies and certainly implantable technologies for pain control
      have a place as 'tools' for the management of cancer, AIDS, and non-malignant
      related pain syndromes. Since these therapies are costly and invasive, they
      should be used only after the failure of more conservative, less invasive and
      less costly therapies. This paper outlines a rational place for the use of
      implantable modalities for the treatment of cancer, AIDS and non-malignant pain. 

PMID- 24573052
TI  - Depression and pain: Assessment and therapeutic strategies.
AB  - Many patients with pain also suffer from depression. The exact relationship
      between these two problems is unclear but it appears that, in many patients, the
      depression may not simply be secondary to the pain. When these problems coexist,
      successful management requires the proper assessment and treatment of both. This
      paper discusses depressive disorders associated with pain and their treatment,
      with special focus on medication management. 

PMID- 24573053
TI  - Visceral pain: From physiology to clinical practice.

PMID- 24573054
TI  - Therapeutic drugs for neuropathic pain.
AB  - Neuropathic pain is common and may be resistant to usual doses of analgesic
      medications. However, an improved understanding of the pathophysiology of
      neuropathic pain and a growing number of adjuvant medications that are useful for
      the treatment of neuropathic pain provide renewed hope for clinicians and their
      patients. It is useful to classify adjuvant analgesic drugs into two broad
      categories. Membrane stabilizing agents, which include the anticonvulsants,
      antiarrhythmics and probably corticosteroids, may act by blocking sodium channels
      on damaged neural membranes. Medications that enhance dorsal horn inhibition,
      which include the antidepressants and some anticonvulsants, may augment biogenic
      amine or GABAergic mechanisms in the dorsal horn of the spinal cord. Current
      evidence regarding efficacy generally does not support the use of one agent over
      another and selection of a particular agent may depend in part on the expected
      side effects or experience with a given drug. For maximum analgesic effect, more
      than one agent may be necessary and to improve therapy and minimize side effects,
      medications generally should be started at lower doses and titrated slowly to
      effect. Although labor-intensive, this strategy may improve compliance and
      optimize patient care. 

PMID- 24573055
TI  - The spinal form of spasticity.

PMID- 24573056
TI  - Pediatric pain management and therapeutic strategies.

PMID- 24573057
TI  - The management of post-operative pain and the rationale for pre-emptive
      analgesia.

PMID- 24573058
TI  - Disarming the dominance of chronic pain.

PMID- 24573060
TI  - Author indexVolume 9 (1997).

PMID- 24573062
TI  - Volume contentsVolume 9 (1997).

PMID- 24573063
TI  - Non-motor symptoms in treated and untreated Chinese patients with early
      Parkinson's disease.
AB  - Non-motor symptoms (NMS) are important preclinical features of Parkinson's
      disease (PD) and have become the leading cause of poor quality of life with
      disease progression. There are little data on how antiparkinsonian medications
      influence the NMS in PD at early stage. In this study, we explored the
      distribution of NMS in treated and untreated PD and investigated the association
      between NMS and antiparkinsonian medications in Chinese patients with early PD.
      Subjects were enrolled from a Chinese PD patient cohort based on 2 clinical
      trials. Face-to-face interviews and evaluations were performed for clinical
      information. NMS were compared in patients with or without antiparkinsonian
      treatment, and between subgroups of dopaminergic medications. Eight hundred and
      sixteen PD patients were enrolled in this study, of whom 428 were newly diagnosed
      PD. Only 5 in 646 patients who completed all these NMS measurements (0.6%) were
      free of NMS. PD patients with antiparkinsonian medications had a significantly
      higher frequency of poor sleep (p = 0.001), depression (p = 0.0001) and
      constipation (p = 0.0001) after adjusted gender, onset age, duration, and Hoehn &
      Yahr stage. Moreover, patients treated by levodopa plus dopamine agonist had a
      higher percentage of bad sleepers (adjusted p = 0.040), and correlation analysis
      revealed that Levodopa Equivalent Dose (LED) was associated with constipation
      (coefficient 0.146, p = 0.005). These findings suggest that although NMS exist in
      the prodromal stage of PD, antiparkinsonian treatment is associated with
      increased frequency of some NMS, which may challenge the management for PD. 

PMID- 24573064
TI  - Coronary artery ectasia is associated with the c.894G>T (Glu298Asp) polymorphism
      of the endothelial nitric oxide synthase gene.
AB  - Coronary artery ectasia (CAE) is characterized by inappropriate dilation of the
      coronary vasculature. The underlying mechanisms of CAE formation are not yet
      entirely known. A polymorphism in the endothelial nitric oxide synthase (eNOS)
      gene, which reduces eNOS activity, might be a risk factor for coronary heart
      diseases. However, its role in CAE is unknown. One of the most studied eNOS gene
      polymorphisms is a c.894G>T polymorphism that results in the conversion of Glu
      (GAG) to Asp (GAT) at position 298. In this study, we investigated the potential
      association between the c.894G>T (Glu298Asp) polymorphism and CAE. The present
      study included 84 subjects from 2,980 consecutive patients in whom elective
      diagnostic coronary angiography was performed. Forty patients with isolated CAE
      and 44 subjects with normal coronary arteries were enrolled. The frequencies of
      the G allele were 78.4% in the control and 57.5% in CAE patients. The TT genotype
      was more frequent in patients with CAE than that in the controls (20% vs. 4.5%, p
      = 0.013). Furthermore, the risk of developing CAE in the presence of the
      homozygous TT genotype was significantly higher in the patients than that in the
      controls (OR = 7.7, 95% CI = 1.44-41.3). The presence of an 894T allele increased
      the risk of CAE 2.8-fold (95% CI = 1.15-6.73; p = 0.027). The frequencies of the
      T allele were 65% in CAE patients and 38.6% in the controls. In conclusion, the
      c.894G>T polymorphism in the eNOS gene may be a risk factor for CAE. 

PMID- 24573066
TI  - Almanac 2013-stable coronary artery disease.

PMID- 24573065
TI  - Prenatal treatment of Down syndrome: a reality?
AB  - PURPOSE OF REVIEW: Down syndrome affects more than 5 million people globally.
      During the last 10 years, there has been a dramatic increase in the research
      efforts focused on therapeutic interventions to improve learning and memory in
      Down syndrome. RECENT FINDINGS: This review summarizes the different functional
      abnormalities targeted by researchers in mouse models of Down syndrome. Three
      main strategies have been used: neural stem cell implantation; environmental
      enrichment and physical exercise; and pharmacotherapy. Pharmacological targets
      include the choline pathway, GABA and NMDA receptors, DYRK1A protein, oxidative
      stress and pathways involved in development and neurogenesis. Many strategies
      have improved learning and memory as well as electrophysiological and molecular
      alterations in affected animals. To date, eight molecules have been tested in
      human adult clinical trials. No studies have yet been performed on infants.
      However, compelling studies reveal that permanent brain alterations originate
      during fetal life in Down syndrome. Early prenatal diagnosis offers a 28 weeks
      window to positively impact brain development and improve postnatal cognitive
      outcome in affected individuals. Only a few approaches (Epigallocatechine
      gallate, NAP/SAL, fluoxetine, and apigenin) have been used to treat mice in
      utero; these showed therapeutic effects that persisted to adulthood. SUMMARY: In
      this article, we discuss the challenges, recent progress, and lessons learned
      that pave the way for new therapeutic approaches in Down syndrome.

PMID- 24573068
TI  - Alkyl chlorido hydridotris(3,5-dimethylpyrazolyl)borate imido niobium and
      tantalum(V) complexes: synthesis, conformational states of alkyl groups in solid
      and solution, X-ray diffraction and multinuclear magnetic resonance spectroscopy
      studies.
AB  - The alkylation of the starting pseudooctahedral dichlorido imido hydridotris(3,5
      dimethylpyrazolyl)borate niobium and tantalum(v) compounds [MTp*Cl2(NtBu)] (M =
      Nb,Ta; Tp* = BH(3,5-Me2C3HN2)3) with MgClR in different conditions led to new
      alkyl chlorido imido derivatives [MTp*ClR(NtBu)] (M = Nb/Ta, R = CH2CH31a/1b,
      CH2Ph 2a/2b, CH2tBu 3a/3b, CH2SiMe34a/4b, CH2CMe2Ph 5a/5b), whereas the dimethyl
      derivatives [MTp*Me2(NtBu)] (M = Nb 6a, Ta 6b) could be isolated as unitary
      species when the reaction was carried out using 2 equivalents of the magnesium
      reagent MgClMe. However, the chlorido methyl [MTp*ClMe(NtBu)] (M = Nb 7a, Ta 7b)
      complexes were obtained by heating at 50  degrees C the dichlorido and dimethyl
      imido complexes mixtures in a 1 : 1 ratio. All of the complexes were studied by
      multinuclear magnetic resonance spectroscopy and the molecular structures of 1b,
      2a/b, 3a/b, 4a and 5a/b were determined by X-ray diffraction methods. In the
      solid state the complexes 1b, 4a and 5a exhibit only a gauche-anti conformation
      and the complexes 2a/b, 3a/b and 5b exhibit only a gauche-syn conformation of the
      alkyl substituents, whereas both conformational states, which do not show mutual
      exchange in the NMR time scale, were observed for 3a/b in a benzene-d6 solution.
      The (15)N chemical shifts of the complexes 1-7 are discussed.

PMID- 24573067
TI  - Punctate palmoplantar keratoderma type 1: a novel AAGAB mutation and efficacy of
      etretinate.

PMID- 24573069
TI  - Normal values for cervical range of motion.
AB  - STUDY DESIGN: Cohort study. OBJECTIVE: To generate normal values for active range
      of motion (ACROM) of the cervical spine in asymptomatic persons. SUMMARY OF
      BACKGROUND DATA: There is a lack of normal values for ACROM based on large groups
      and stratified for different age categories. METHODS: Four hundred asymptomatic
      persons were included, 100 for each decade of age from 20 years to 60 years and
      in each subgroup 50 males and 50 females. ACROM was measured with the cervical
      range of motion (CROM) device. Analysis of variance and the Scheffe post hoc test
      was used to investigate the differences of ACROM between the decades of age.
      Linear regression analysis was performed to examine the influence of age and sex
      on ACROM. RESULTS: The results of this study show that the ACROM decreases
      significantly in persons older than 50 years for all directions except extension
      and side flexion compared with that in the subgroup aged 40 to 50. Age had an
      overall significant effect on the ACROM for all directions. Sex proved to have no
      significant effect on the ACROM. CONCLUSION: Normal values were established for
      ACROM in a group of 400 persons without neck complaints. It was demonstrated that
      age has a significant influence on the ACROM, but sex has no influence. LEVEL OF
      EVIDENCE: N/A.

PMID- 24573070
TI  - Thoracolumbar kyphosis in treated mucopolysaccharidosis 1 (Hurler syndrome).
AB  - STUDY DESIGN: A retrospective radiographical follow-up study of thoracolumbar
      deformity in 33 children with mucopolysaccharidosis 1 (Hurler syndrome).
      OBJECTIVE: To report the severity, natural history, risk factors for progression,
      and results of intervention for thoracolumbar kyphosis in children with Hurler
      syndrome. SUMMARY OF BACKGROUND DATA: Literature on the subject of thoracolumbar
      kyphosis in Hurler syndrome and its treatment is limited to small case series.
      The natural history and thus indications for intervention are unknown. METHODS:
      Patients who had been treated with bone marrow transplantation and/or enzyme
      replacement therapy were followed up with erect radiographs of the spine. Mean
      follow-up period was 3.5 years (range, 2-12 yr). Radiographs were retrieved and
      analyzed retrospectively. Seven patients underwent varied forms of surgical
      intervention for progressive deformity, the technique and principles of which are
      described. RESULTS: The thoracolumbar kyphosis on initial radiographs obtained at
      a mean age of 17 months measured 38 degrees  (95% confidence interval, 34 degrees
      -42 degrees ). Fifteen of the 33 patients (45%) followed for more than 2 years
      developed a deformity that made a progression of more than 10 degrees . The
      magnitude of the initial deformity was predictive of whether the deformity
      progressed (univariate analysis, P < 0.001). An initial kyphosis angle greater
      than 45 degrees  was predictive of progression of more than 10 degrees  with
      sensitivity of 67% and specificity of 88%. All patients who underwent surgical
      intervention had sustained improvement in the magnitude of thoracolumbar
      deformity. CONCLUSION: Thoracolumbar kyphosis in Hurler syndrome is of variable
      severity with an average deformity, in our series, of 38 degrees  at a mean age
      of 17 months. Forty-five percent of patients developed progression of greater
      than 10 degrees . Patients with an initial deformity greater than 45 degrees 
      seemed to be more likely to progress. Surgical interventions in the form of
      anterior fusion, combined anterior and posterior surgery and use of the vertical
      expandable prosthetic titanium rib provided good correction. LEVEL OF EVIDENCE:
      N/A.

PMID- 24573071
TI  - Cost and value of spinal deformity surgery.
AB  - STUDY DESIGN: Literature review. OBJECTIVE: To assess (1) quality of life in
      patients with adult scoliosis who underwent nonoperative and/or surgical
      treatment, and (2) cost-effectiveness of different scoliosis treatment
      modalities. SUMMARY OF BACKGROUND DATA: Recently, there has been an interest in
      examining quality of life of patients undergoing treatment for adult scoliosis,
      comparing the value of nonoperative versus operative management. This article
      reviews the current literature on treatment of adult scoliosis, in the hopes of
      drawing conclusions for the best approach to these patients. METHODS: MEDLINE and
      PubMed databases were searched to identify articles. Health-related quality of
      life measures included Oswestry Disability Index scores, Scoliosis Research
      Society (SRS) instrument scores, 12-Item Short Form Health Survey, and numerical
      rating scale for leg and/or back pain. Studies included were those involving
      patients with adult scoliosis who underwent primary surgery or nonoperative
      management. The studies that focused on the change in validated outcome scores
      from the onset of the study to final follow-up were found to be valuable. Studies
      on predominantly adolescent scoliosis and those that only measured postoperative
      outcomes scores were excluded. RESULTS: The SRS-22, Oswestry Disability Index, 12
      Item Short Form Health Survey, and numerical rating scale were found to be
      validated for measuring quality of life in patients with scoliosis. Thirteen
      studies were included, which evaluated changes in health-related quality of life
      outcomes from baseline in surgical and nonsurgical treatment of adult scoliosis.
      There was a trend toward improved quality of life measures in patients undergoing
      surgical treatment for adult scoliosis. CONCLUSION: Adults with painful and
      disabling scoliosis may benefit from surgical treatment compared with nonsurgical
      treatment, given the proper indications. Nonsurgical treatment does not seem to
      be cost-effective and has not shown to have a positive impact on quality of life,
      although there is a possibility that patients' health may have deteriorated if
      they did not receive the nonsurgical treatment. Future prospective studies
      focusing on the cost-effectiveness of adult scoliosis treatment and improvement
      of quality of life are needed to confirm the assertion of the current
      retrospective literature that surgery provides better quality of life than
      nonoperative treatment. LEVEL OF EVIDENCE: N/A.

PMID- 24573072
TI  - Prevalence, distribution, and morphology of thoracic ossification of the
      posterior longitudinal ligament in Japanese: results of CT-based cross-sectional
      study.
AB  - STUDY DESIGN: A cross-sectional study. OBJECTIVE: To gain an insight into the
      prevalence, morphology, and distribution of thoracic ossification of the
      posterior longitudinal ligament of the spine (T-OPLL) by computed tomography (CT)
      and review of the literature. SUMMARY OF BACKGROUND DATA: The epidemiology and
      cause of T-OPLL remains obscure. To date, to the best of our knowledge, there is
      no study that has comprehensively evaluated the thoracic spine by CT to assess
      the prevalence, distribution, and morphology of T-OPLL in a sufficiently large
      size of sample with wide distribution of age. METHODS: The participants of this
      study were the patients who have undergone chest CT for the examination of
      pulmonary diseases in our institute. The patients with previous thoracic spine
      surgery and younger than 15 years were excluded. Prevalence, distribution, and
      morphology of T-OPLL were reviewed. RESULTS: A total of 3013 patients (1261
      females and 1752 males) with the mean age of 65 years were recruited. The CT
      based evidence of T-OPLL was noted in 56 (38 females and 18 males) individuals
      (1.9%). Most frequently encountered type was liner type, followed by continuous
      cylindrical type and mixed type. Continuous waveform and beaked type were less
      frequently encountered. Statistical analyses revealed that T-OPLL was noted at a
      significantly higher rate among the females. The mean age of T-OPLL-positive
      males was significantly higher than that of T-OPLL-negative males. Furthermore,
      there was significant difference of body mass index between T-OPLL-positive and T
      OPLL-negative individuals. Most of T-OPLLs were confirmed in higher or middle
      thoracic regions and the highest peak was found at T3-T4. T-OPLL was noted after
      the age of 40 years with the peak distribution found at the age of 60 years.
      CONCLUSION: The prevalence of T-OPLL in Japanese was 1.9%. Further studies that
      characterize definitive subtypes of T-OPLL on CT are warranted so as to establish
      possible association between clinical manifestations and size and/or subtypes of
      T-OPLL. LEVEL OF EVIDENCE: N/A.

PMID- 24573073
TI  - Complications after lumbar spine surgery between teaching and nonteaching
      hospitals.
AB  - STUDY DESIGN: Retrospective national database analysis. OBJECTIVE: A national
      population-based database was analyzed to characterize the perioperative
      complications of lumbar spine procedures performed at teaching and nonteaching
      hospitals. SUMMARY OF BACKGROUND DATA: Perception biases exist regarding the
      complications of lumbar spine surgery based upon the hospital teaching
      environment. METHODS: Data from the Nationwide Inpatient Sample was queried from
      2002-2011. Patients undergoing an anterior lumbar interbody fusion, posterior
      lumbar interbody fusion, anterior/posterior lumbar fusion, or lumbar
      decompression to treat lumbar degenerative pathology were identified and
      separated into cohorts based upon the teaching status of the hospital. Patient
      demographics, Charlson Comorbidity Index, length of stay, complications,
      mortality, and costs were assessed. RESULTS: A total of 658,616 lumbar procedures
      were identified from 2002-2011, of which 367,875 (55.9%) were performed at
      teaching hospitals. An older patient population comprised the teaching hospital
      cohort and demonstrated a greater comorbidity burden than the nonteaching group
      (Charlson Comorbidity Index 2.90 vs. 2.55; P < 0.001). In addition, the teaching
      hospital cohort was associated with a significantly greater number of multilevel
      fusion cases (P < 0.001) and incurred a greater mean length of stay (3.7 vs. 3.0
      d; P < 0.001). Patients treated at teaching hospitals demonstrated a
      significantly greater incidence of postoperative pulmonary embolism, deep vein
      thrombosis, infection, and neurological complications than the nonteaching cohort
      (P < 0.001). Overall, there were no significant differences in the mean total
      hospital costs or mortality between the hospital cohorts. Regression analysis
      demonstrated that teaching status was not a significant predictor of mortality
      (OR, 1.02; confidence interval 0.8-1.2; P = 0.8). CONCLUSION: Patients treated in
      teaching hospitals for lumbar spine surgery incurred a longer hospitalization and
      a greater incidence of postoperative complications including pulmonary embolism,
      deep vein thrombosis, infection, and neurological events. These findings may be
      explained by an increased complexity of procedures performed at teaching
      hospitals along with an older and a more comorbid patient population. Despite
      these differences, the teaching status was not a significant predictor of in
      hospital mortality after a lumbar spine surgery. LEVEL OF EVIDENCE: 3.

PMID- 24573074
TI  - Clinical and radiographic outcomes after 3-column osteotomies with 5-year follow
      up.
AB  - STUDY DESIGN: Retrospective review of prospective database. OBJECTIVE: To
      investigate long-term results after 3-column osteotomies (3-CO). SUMMARY OF
      BACKGROUND DATA: Short-term studies have noted improved outcomes and alignment
      after 3-CO, but there is a paucity of long-term studies with a large group of
      patients. METHODS: An analysis of 126 patients who underwent a 3-CO (pedicle
      subtraction osteotomy [N = 101]/vertebral column resection [N = 25]) with minimum
      5-year follow-up was performed at a single institution. The mean age was 48 years
      (range, 8-79 yr) and average follow-up was for 7 years (range, 5-14 yr). Oswestry
      Disability Index and Scoliosis Research Society (SRS) scores and radiographical
      parameters were assessed at baseline, 6 weeks, and 1, 2, 3, and/or 5 years
      postoperatively and complications were recorded. RESULTS: Sagittal alignment
      improved at all postoperative time points from baseline (mean, 117 mm), but
      diminished from 6 weeks (mean, 24 mm) to 5 years (mean, 41 mm; P = 0.03). Average
      coronal alignment was improved from baseline (27 mm) at 6 weeks (18 mm; P =
      0.003) and 5 years postoperatively (19 mm; P = 0.007), with no deterioration
      between 6 weeks and 5 years postoperatively (P = 0.9). Major surgical
      complications occurred in 36% (n = 45) and major repeat surgery was performed in
      28% (n = 35). Significant improvements (P < 0.05) in Oswestry Disability Index
      and all SRS domain scores were found at each time point. All mean outcome scores
      at 5 years postoperatively exceeded minimal clinically important difference
      thresholds except the SRS function domain. Improvement in outcomes at 5 years
      postoperatively was similar in groups with major surgical complications versus
      those without and in those with reoperation versus those without. CONCLUSION:
      This study of 126 patients undergoing 3-CO found significant and sustained
      improvements in Oswestry Disability Index and SRS scores and sagittal alignment
      at a minimum 5 years postoperatively. This demonstrates the durability of these
      complex spinal reconstructions, even surprisingly in those patients having a
      major complication and/or revision surgery. LEVEL OF EVIDENCE: 4.

PMID- 24573075
TI  - Single-stage anterior high sacrectomy for locally recurrent rectal cancer.
AB  - STUDY DESIGN: A review of prospectively collected data on a consecutive series of
      patients undergoing single-stage anterior high sacrectomy for locally recurrent
      rectal carcinoma (LRRC). OBJECTIVE: To determine the clinical outcome of patients
      who underwent anterior high sacrectomy for LRRC. SUMMARY OF BACKGROUND DATA: High
      sacrectomy for oncological resection remains technically challenging. Surgery has
      the potential to achieve cure in carefully selected patients. Complete (R0) tumor
      excision in LRRC may require sacrectomy. High sacral resections (S3 and above)
      typically require a combined anterior/supine and posterior/prone procedure. We
      investigated our experience performing single-stage anterior high sacrectomy for
      LRRC. METHODS: A consecutive series of patients with LRRC without systemic
      metastases who underwent resection with curative intent requiring high sacrectomy
      were identified. A review of a prospectively maintained colorectal and spine
      cancer database data was performed. An oblique dome high sacral osteotomy was
      performed during a single-stage anterior procedure. Outcome measures included
      surgical resection margin status, hospital length of stay, postoperative
      complications, physical functioning status, and overall survival. RESULTS:
      Nineteen consecutive patients were treated between 2002 and 2011. High sacrectomy
      was performed at sacral level S1-S2 in 4 patients, S2-S3 in 9 patients, and
      through S3 in 6 patients. An R0 resection margin was achieved histologically in
      all 19 cases. There was 1 early (<30 d) postoperative death (1/19, 5%). At median
      follow-up of 38 months, 13 patients had no evidence of residual disease, 1 was
      alive with disease, and 4 had died of disease. Morbidities occurred in 15 of the
      19 patients (79%). CONCLUSION: Although high sacrectomy may require a combined
      anterior and posterior surgical approach, our series demonstrates the feasibility
      of performing single-stage anterior high sacrectomy in LRRC, with acceptable
      risks and outcomes compared with the literature. The procedure described by us
      for LRRC lessens the need for a simultaneous or staged prone posterior resection,
      with favorable R0 tumor resections, patient survival, and clinical outcomes.
      LEVEL OF EVIDENCE: N/A.

PMID- 24573076
TI  - Letter.

PMID- 24573078
TI  - Responsiveness and interpretability of the Portuguese version of the Quebec Back
      Pain Disability Scale in patients with chronic low back pain.
AB  - STUDY DESIGN: A prospective cohort study with a 6-week follow-up of patients with
      chronic low back pain undergoing physiotherapy. OBJECTIVE: To examine the
      responsiveness of the Portuguese version of the Quebec Back Pain Disability Scale
      (QBPDS-PT), and to determine the minimal clinically important difference, minimal
      detectable change (MDC), and floor/ceiling effects. SUMMARY OF BACKGROUND DATA:
      Measuring change over time is critical to assess the effectiveness of a
      physiotherapy intervention or to distinguish individual differences in response
      to treatment. METHODS: One hundred thirty-two patients were recruited from 16
      outpatient clinics in 7 different regions of Portugal. A final sample of 120
      patients completed the QBPDS-PT twice: at the baseline and after 6 weeks of
      physiotherapy treatment. The patient global impression of change scale was used
      as an external criterion measure to distinguish between improved or nonimproved
      patients' scores between baseline and follow-up. The responsiveness of the QBPDS
      PT was assessed through correlation coefficient and receiver operating
      characteristics curves. The minimal clinically important difference was estimated
      by the receiver operating characteristics curve method and the MDC through the
      standard error of measurement. RESULTS: The scale revealed moderate
      responsiveness (rho = 0.426 and area under the curve = 0.741; 95% confidence
      interval: 0.645-0.837). The MDC achieved 19 points, whereas the minimal
      clinically important difference was found to be 6.5 points (area under the curve
      = 0.741, sensitivity = 72%, specificity = 71%). A floor effect was founded with
      15.8% of the participants reporting values within the MDC at the lower end of the
      available range of scores. For the highest baseline scores of QBPDS-PT (>=34
      points) the optimal cutoff point was found to be 10.5 points (area under the
      curve = 0.738, sensitivity = 73%, specificity = 67%). CONCLUSION: The QBPDS-PT
      demonstrated moderate levels of responsiveness, and is recommended to measure
      change in disability in patients with chronic low back pain after physiotherapy
      intervention. LEVEL OF EVIDENCE: N/A.

PMID- 24573080
TI  - Photo quiz: A patient with ulcerated nodules on his face.

PMID- 24573083
TI  - Even an old technique is suitable in the molecular world of science: the everted
      sac preparation turns 60 years old.
AB  - An old proverb states "necessity is the mother of invention." This certainly
      holds true in science as one pursues research questions. Experimental techniques
      have evolved as scientists have asked more specific research questions. Indeed,
      techniques such as the Ussing chamber, the perfused renal tubule preparation,
      patch-clamp, polymerase chain reaction, and site-directed mutagenesis have been
      developed over the past 60 years. However, sometimes, simple techniques may be
      useful and still very informative, and this certainly applies to intestinal
      physiology. Indeed, Gerald Wiseman and Thomas Hastings Wilson described the
      intestinal everted sac preparation some 60 years ago. Since then, this technique
      has been used for numerous research purposes including determining ion, amino
      acid, water and solute transport across the intestinal epithelium; and drug
      metabolism, absorption, and interactions in pharmaceutical/pharmacological
      research and even in education. This article provides a historical review of the
      development of the in vitro intestinal preparation that led to the everted sac
      preparation and its use in science. 

PMID- 24573084
TI  - Angiogenic microenvironment augments impaired endothelial responses under
      diabetic conditions.
AB  - Diabetes-induced cardiomyopathy is characterized by cardiac remodeling, fibrosis,
      and endothelial dysfunction, with no treatment options currently available.
      Hyperglycemic memory by endothelial cells may play the key role in microvascular
      complications in diabetes, providing a potential target for therapeutic
      approaches. This study tested the hypothesis that a proangiogenic environment can
      augment diabetes-induced deficiencies in endothelial cell angiogenic and
      biomechanical responses. Endothelial responses were quantified for two models of
      diabetic conditions: 1) an in vitro acute and chronic hyperglycemia where normal
      cardiac endothelial cells were exposed to high-glucose media, and 2) an in vivo
      chronic diabetes model where the cells were isolated from rats with type I
      streptozotocin-induced diabetes. Capillary morphogenesis, VEGF and nitric oxide
      expression, cell morphology, orientation, proliferation, and apoptosis were
      determined for cells cultured on Matrigel or proangiogenic nanofiber hydrogel.
      The effects of biomechanical stimulation were assessed following cell exposure to
      uniaxial strain. The results demonstrate that diabetes alters cardiac endothelium
      angiogenic response, with differential effects of acute and chronic exposure to
      high-glucose conditions, consistent with the concept that endothelial cells may
      have a long-term "hyperglycemic memory" of the physiological environment in the
      body. Furthermore, endothelial cell exposure to strain significantly diminishes
      their angiogenic potential following strain application. Both diabetes and strain
      associated deficiencies can be augmented in the proangiogenic nanofiber
      microenvironment. These findings may contribute to the development of novel
      approaches to reverse hyperglycemic memory of endothelium and enhance
      vascularization of the diabetic heart, where improved angiogenic and
      biomechanical responses can be the key factor to successful therapy. 

PMID- 24573086
TI  - Fingerprints of hSGLT5 sugar and cation selectivity.
AB  - Sodium glucose cotransporters (SGLTs) mediate the translocation of carbohydrates
      across the brush border membrane of different organs such as intestine, kidney,
      and brain. The human SGLT5 (hSGLT5), in particular, is localized in the kidney
      were it is responsible for mannose and fructose reabsorption from the glomerular
      filtrate as confirmed by more recent studies on hSGLT5 knockout mice. Here we
      characterize the functional properties of hSGLT5 expressed in a stable T-Rex-HEK
      293 cell line using biochemical and electrophysiological assays. We confirmed
      that hSGLT5 is a sodium/mannose transporter that is blocked by phlorizin. Li(+)
      and H(+) ions were also able to drive mannose transport, and transport was
      electrogenic. Our results moreover indicate that substrates require a pyranose
      ring with an axial hydroxyl group (-OH) on carbon 2 (C-2). Compared with
      Na(+)/glucose cotransport, the level of function of Na(+)/mannose cotransport in
      rat kidney slices was low.

PMID- 24573087
TI  - Label-free quantitative proteomic analysis of the YAP/TAZ interactome.
AB  - The function of an individual protein is typically defined by protein-protein
      interactions orchestrating the formation of large complexes critical for a wide
      variety of biological processes. Over the last decade the analysis of purified
      protein complexes by mass spectrometry became a key technique to identify protein
      protein interactions. We present a fast and straightforward approach for analyses
      of interacting proteins combining a Flp-in single-copy cellular integration
      system and single-step affinity purification with single-shot mass spectrometry
      analysis. We applied this protocol to the analysis of the YAP and TAZ
      interactome. YAP and TAZ are the downstream effectors of the mammalian Hippo
      tumor suppressor pathway. Our study provides comprehensive interactomes for both
      YAP and TAZ and does not only confirm the majority of previously described
      interactors but, strikingly, revealed uncharacterized interaction partners that
      affect YAP/TAZ TEAD-dependent transcription. Among these newly identified
      candidates are Rassf8, thymopoetin, and the transcription factors CCAAT/enhancer
      binding protein (C/EBP)beta/delta and core-binding factor subunit beta (Cbfb). In
      addition, our data allowed insights into complex stoichiometry and uncovered
      discrepancies between the YAP and TAZ interactomes. Taken together, the stringent
      approach presented here could help to significantly sharpen the understanding of
      protein-protein networks.

PMID- 24573085
TI  - Activation of Notch signaling by short-term treatment with Jagged-1 enhances
      store-operated Ca(2+) entry in human pulmonary arterial smooth muscle cells.
AB  - Notch signaling plays a critical role in controlling proliferation and
      differentiation of pulmonary arterial smooth muscle cells (PASMC). Upregulated
      Notch ligands and Notch3 receptors in PASMC have been reported to promote the
      development of pulmonary vascular remodeling in patients with pulmonary arterial
      hypertension (PAH) and in animals with experimental pulmonary hypertension.
      Activation of Notch receptors by their ligands leads to the cleavage of the Notch
      intracellular domain (NICD) to the cytosol by gamma-secretase; NICD then
      translocates into the nucleus to regulate gene transcription. In this study, we
      examined whether short-term activation of Notch functionally regulates store
      operated Ca(2+) entry (SOCE) in human PASMC. Treatment of PASMC with the active
      fragment of human Jagged-1 protein (Jag-1) for 15-60 min significantly increased
      the amplitude of SOCE induced by passive deletion of Ca(2+) from the
      intracellular stores, the sarcoplasmic reticulum (SR). The Jag-1-induced
      enhancement of SOCE was time dependent: the amplitude was maximized at 30 min of
      treatment with Jag-1, which was closely correlated with the time course of Jag-1
      mediated increase in NICD protein level. The scrambled peptide of Jag-1 active
      fragment had no effect on SOCE. Inhibition of gamma-secretase by N-[N-(3,5
      difluorophenacetyl-L-alanyl)]-S-phenylglycine t-butyl ester (DAPT) significantly
      attenuated the Jag-1-induced augmentation of SOCE. In addition to the short-term
      effect, prolonged treatment of PASMC with Jag-1 for 48 h also markedly enhanced
      the amplitude of SOCE. These data demonstrate that short-term activation of Notch
      signaling enhances SOCE in PASMC; the NICD-mediated functional interaction with
      store-operated Ca(2+) channels (SOC) may be involved in the Jag-1-mediated
      enhancement of SOCE in human PASMC.

PMID- 24573088
TI  - Defining the relationship between average glucose and HbA1c in patients with type
      2 diabetes and chronic kidney disease.
AB  - AIMS: To examine the relationship between average glucose (AG) and HbA1c in
      patients with and without chronic kidney disease (CKD) and type 2 diabetes.
      MATERIALS AND METHODS: 43 patients with diabetes and CKD (stages 3-5) with stable
      glycaemic control, and glucose-lowering and erythropoiesis stimulating agent
      (ESA) doses, were prospectively studied for 3 months and compared to 104 age
      matched controls with diabetes, without CKD from the ADAG study. Over 3 months,
      AG was calculated from 7 to 8 point self-monitored blood glucose measurements
      (SMBG) and from continuous glucose monitoring (CGMS), and mean HbA1c was
      calculated from 4 measurements. AG and HbA1c relationships were determined using
      multivariable linear regression analyses. RESULTS: The CKD and non-CKD groups
      were well matched for age and gender. Mean AG tended to be higher (p=0.08) but
      HbA1c levels were similar (p=0.68) in the CKD compared with non-CKD groups. A
      linear relationship between AG and HbA1c was observed irrespective of the
      presence and stage of CKD. The relationship was weaker in patients with stage 4-5
      CKD (non-CKD R2=0.75, stage 3 CKD R2=0.79 and stage 4-5 CKD R2=0.34, all p<0.01).
      The inclusion of ESA use in the model rendered the effect of CKD stage
      insignificant (R2=0.67, p<0.01). CONCLUSIONS: In patients with type 2 diabetes
      and CKD there is a linear relationship between HbA1c and AG that is attenuated by
      ESA use, suggesting that ESA results in a systematic underestimation of AG
      derived from HbA1c.

PMID- 24573089
TI  - Nanomembrane-based materials for Group IV semiconductor quantum electronics.
AB  - Strained-silicon/relaxed-silicon-germanium alloy (strained-Si/SiGe)
      heterostructures are the foundation of Group IV-element quantum electronics and
      quantum computation, but current materials quality limits the reliability and
      thus the achievable performance of devices. In comparison to conventional
      approaches, single-crystal SiGe nanomembranes are a promising alternative as
      substrates for the epitaxial growth of these heterostructures. Because the
      nanomembrane is truly a single crystal, in contrast to the conventional SiGe
      substrate made by compositionally grading SiGe grown on bulk Si, significant
      improvements in quantum electronic-device reliability may be expected with
      nanomembrane substrates. We compare lateral strain inhomogeneities and the local
      mosaic structure (crystalline tilt) in strained-Si/SiGe heterostructures that we
      grow on SiGe nanomembranes and on compositionally graded SiGe substrates, with
      micro-Raman mapping and nanodiffraction, respectively. Significant structural
      improvements are found using SiGe nanomembranes. 

PMID- 24573091
TI  - Nucleation & crystallisation.

PMID- 24573092
TI  - Introduction: lumbar spinal orthotics.
AB  - Considerable medical literature has been devoted to the use of spinal orthotics
      in the treatment of conditions effecting the lumbar spine. Nonetheless, when it
      comes to clinical application, controversy and misunderstanding continue to
      exist. This issue of The journal of Back and Musculoskeletal Rehabilitation
      attempts to reexplore this knowledge base and reexamine the clinical utility of
      lumbar spinal orthotics. This introductory article briefly covers the history and
      nomenclature of spinal orthotics with a more in-depth look at the mechanical
      principles of spinal orthotics. Finally, the more commonly perscribed orthotic
      designs are presented pictorially. 

PMID- 24573093
TI  - Elastic Supports and Body SuitsEffective Energy-Storing Garments.
AB  - The principles behind the use of lumbar supports have changed drastically in
      recent years. Once used for immobilization, lumbar supports and body suits are
      now being used to encourage mobility and return to function in low back pain
      patients. Modern concepts regarding the stored/strain energy of elastic garments
      are introduced, followed by a discussion of how body suits and elastic supports
      utilize these properties to assist the low back pain patient. A number of
      different types of elastic garments are illustrated.The use of rigid corsets for
      low back pain began around the turn of the century with the use of plaster
      jackets. More recently, heavy nylon, steel stays, and complex plastics have been
      used for the same purpose. The rationale for this type of immobilization includes
      assistance for weakened muscles, protection from injury, correction of deformity,
      control of pain, restriction of spinal movements, and increased temperature.1
      4Some of these proposed physiologic mechanisms have been investigated, including
      intraabdominal and intradiscal pressure changes, paraspinal electro myographic
      (EMG) activity, and intersegmental as well as gross spinal motions.4-9 The
      results ofthese studies have been equivocal, as have the findings of clinical
      trials investigating the efficacy of rigid orthoses.10-15 Further, certain
      disadvantages to the use of rigid orthoses have been described, including
      possible muscle atrophy and dependency. Also, because of the discomfi)rt of the
      devices and the resultant interference with activities of daily living, patient
      compliance can be poor.16Corsets and other similar rigid supports are not
      commonly used now, except for a few special cases. Elastic body suits or supports
      are replacing the rigid-backed brace, and the emphasis is shifting from
      immobilization to assisted mobility and increased function. These new garments
      are comfortable, and the patient is almost unaware of their presence.In this
      article the principles of stored or strain (elastic) energy will be reviewed,
      followed by a discussion of the merits of its use in the back pain patient. We
      will also illustrate some types of elastic garments available today. 

PMID- 24573094
TI  - Regarding the controversy of lumbosacral supports and braces - an update.
AB  - Many health care practitioners believe lumbosacral supports and braces can be
      used effectively in treatment and prevention of musculoskeletal disorders of the
      lumbar spine.Ninety-nine percent of 3,410 orthopedic surgeons surveyed in the
      United States reported prescribing spinal orthoses.1 While there is no hard
      scientific evidence of the clinical effectiveness of lumbosacral supports and
      braces as a group, there are retrospective studies that have documented
      acceptance by patients and improvement of symptoms in from 30% to 80% of the
      cases.2-4The lower lumbar region is of particular interest because most disorders
      occur in one or both of the lower two segments. The use of supports and braces in
      the management of many common disorders will be discussed. Disorders of the
      sacroiliac joints, spinal fractures, postsurgical management, and corrective
      braces used in the treatment of disorders such as scoliosis and kyphosis are not
      within the scope of this article.Medical as well as industrial health and safety
      literature is filled with the pros and cons of using lumbar supports and braces.
      Certain factual information concerning the effects of back supports and braces
      has been known fix many years, while certain other effects remain unclear. While
      it is true that we have not made many recent discoveries concerning the effects
      of back supports, we have seen a renewed interest in their use. This renewed
      interest seems to focus on prevention as well as treatment, as is especially
      evident in business and industry.There also seems to be increased awareness and
      evidence of back injuries in sports. This has created interest in and use of back
      supports, and has led to development of new concepts and designs of back
      supports.Perhaps another reason for the renewed interest in back supports and
      braces has to do with the recent changes in attitudes toward the treatment of
      back disorders in general. Most experts now agree that almost all back disorders
      can be treated most effectively with early intervention of exercise and patient
      education. We no longer tell the patient to rest, take it easy, and wait until he
      or she is completely free of pain before starting exercises and activities. Many
      practitioners are recognizing that placing a back support on a patient often
      assists him or her in returning to full function sooner, avoiding the well
      documented harmfi.il effects of prolonged immobilization and inactivity. 

PMID- 24573095
TI  - Sacroiliac Joint DysfunctionA New Perspective.
AB  - The sacroiliac (SI) joint as a primary source of low back pain is a resurgent,
      yet controversial subject. In 1905, Goldthwaite proposed that the sacroiliac
      joint could be a physiologic pain generator independent of pregnancy.1 The role
      of the sacroiliac joint fell into obscurity over the ensuing decades, with the
      discovery of such tangible entities (with accepted pathophysiology) as the
      herniated nucleus pulposus,2 and spinal stenosis.3 Accordingly, there is a
      paucity of basic and clinical science information available to aid physicians in
      understanding the biomechanics, diagnosis, and rehabilitation of sacroiliac joint
      dysfunction. 

PMID- 24573090
TI  - Founder effect confirmation of c.241A>G mutation in the L2HGDH gene and
      characterization of oxidative stress parameters in six Tunisian families with L-2
      hydroxyglutaric aciduria.
AB  - L-2-hydroxyglutaric aciduria (L2HGA) is an autosomal recessive neurometabolic
      disorder characterized essentially by the presence of elevated levels of L-2
      hydroxyglutaric acid (LGA) in plasma, cerebrospinal fluid and urine. L2HGA is
      caused by a deficiency in the L2-Hydroxyglutaric dehydrogenase (L2HGDH) enzyme
      involved in the oxidation of LGA to the alpha 2-ketoglutarate. LGA has been
      proposed as an endo- and exogenous cytotoxic organic acid that induces free
      radical formation and generation of reactive oxygen species (ROS). In this
      report, we analyzed 14 L2HGA patients belonging to six unrelated consanguineous
      families the south of Tunisia. The patients were diagnosed with L2HGA disease
      confirmed on the presence of high level of LGA in urine. We analyzed the L2HGDH
      gene in all probands and identified the same c.241A>G homozygous mutation, which
      was previously reported in Tunisia. We also used intragenic single nucleotide
      length polymorphisms (SNPs) and two extragenic microsatellites flanking the
      L2HGDH gene to confirm the founder effect of c.241A>G mutation in the 14 studied
      cases. In addition, we carried out the measurement of the oxidative stress
      parameters in the plasma of L2HGA patients which revealed a significant increase
      in the malondialdehyde levels (MDA), a biomarker of lipid peroxydation, and the
      reduced glutathione (GSH). A diminution of the antioxidant enzyme activities
      including superoxide dismutase (SOD), glutathione peroxidase (GPx), was also
      observed. 

PMID- 24573096
TI  - Spinal OrthoticsSelective Use in Rehabilitation of Vertebral Osteoporosis.
AB  - Symptomatic involutional osteoporosis is a significant clinical problem. The
      prevalence of radiographic vertebral compression fractures (VCF) reached 26% in a
      rigorous population study of men and women more than 50 years old.1 However, only
      an estimated 8% of the total affected population actually seek medical
      attention.2-4 Investigations of effective medical therapy have been extensive,
      while sound studies of the physical therapeutic measures have been relatively
      few.5-10Pain and loss of functional mobility result from this disorder. Kyphosis,
      with or without vertebral compression fracture, is the major structural culprit
      that produces these disabling clinical problems. Spinal orthoses are used
      clinically for mechanical support and pain relief of osteoporosis.5,11-13
      However, little research exists on the efficacy of orthotics in osteoporosis.
      This article provides a practical approach to guide the practitioner in orthotic
      selection for selected patients. New concepts presented may stimulate further
      research interest and more appropriate orthosis prescription. By focusing on
      level of fracture, biomechanical deficits, and physiatric team mangement, the end
      product can better satisfy the patient. 

PMID- 24573097
TI  - The use and abuse of ankle supports in sports injuries.
AB  - The use of ankle bracing, taping, and wrapping for athletic injuries is both
      overused and underused. The overuse occurs in patients who don't need ankle
      support at all, or who don't need it anymore. Underuse occurs in patients who
      could potentially return to activity sooner with the extra support.It is now well
      established and accepted that prolonged immobilization of a body part brings with
      it a number of deleterious effects. Immobilized animals have been shown to have
      decreased strength of muscles, bones, tendons, and ligaments.1-3 Immobility
      adversely affects the healing process and has been shown to decrease ligamentous
      tissue, DNA, and collagen synthesis, and to decrease tensile strength compared to
      ligaments in mobilized rats.4 Similar effects are seen in humans. Proprioception
      is felt to be impaired after immobilization of the ankle,5-8 and persistent
      atrophy of the muscles may ensue.9 Weak muscles and poor proprioception
      predispose the athlete to further injury. Thus, it is clear that immobilizing
      joints as a part of treatment brings with it morbidity of its own. That is not to
      say that it is never necessary and useful. Certainly an unstable joint needs to
      be stabilized, but in recent years the emphasis has shifted from complete
      immobilization to providing support in only the unstable planes, allowing
      functional activity to occur in the stable planes. Bracing, taping, and wrapping
      are increasingly used to provide such support. 

PMID- 24573100
TI  - From the editor.

PMID- 24573098
TI  - Juxtafacet cysts as a cause of low back pain.
AB  - A case of persistent low back pain occurring in association with facet joint
      synovial cysts is presented. A history of low back pain and negative plain
      radiographs illustrate the nonspecific nature of the problem these cysts cause.
      Magnetic resonance imaging (MRI) clearly demonstrates the presence of lumbar
      facet joint cysts. Our patient underwent a L5-S1 laminectomy prior to presenting
      with a new episode of low back pain. Workup, including computed tomography (CT)
      scan and MRI, confirmed the presence of bilateral synovial cysts at the L4-5
      level. Our patient exhibited a partial clinical improvement after surgical
      excision of bilateral facet joint cysts.Intraspinal synovial or ganglion cysts of
      the facet joints are rarely diagnosed. They originate from the synovium of the
      facet articulation. They can be a source of low back pain1 and present an
      important diagnostic and therapeutic challenge. Their presence can be easily
      overlooked using standard radiological techniques2 which may only demonstrate
      nonspecific degenerative changes such as disc space narrowing and osteophytes. If
      the patient undergoes surgery and the cyst is not identified preoperatively, the
      patient may be left with persistent back pain. Computed tomography scan and
      myelogram have been shown to demonstrate cystic lesions with calcified walls
      typical of facet joint cysts.3,4 In our case MRI definitively identified what was
      suspected on the CT scan. It is proposed that MRI is also a valuable, if not
      better imaging technique of the identification of these cysts. 

PMID- 24573101
TI  - Introduction.

PMID- 24573102
TI  - Communication and Medical DevicesA Clarification.

PMID- 24573103
TI  - beta3GnT8 regulates the metastatic potential of colorectal carcinoma cells by
      altering the glycosylation of CD147.
AB  - Aberrant glycosylation of cell surface glycoproteins is commonly associated with
      the invasion and metastasis of colorectal carcinomas, which can be attributed to
      the upregulated expression of glycosyltransferases. Therefore, elucidation of
      glycosyltransferases and their substrates may improve our understanding of their
      roles in tumor metastasis. beta-1,3-N-acetylglucosaminyltransferase-8 (beta3GnT8)
      is a key enzyme that catalyzes the formation of poly-N-acetyllactosamine
      (polylactosamine) chains on beta1,6-branched N-glycans in vitro, which is also
      involved in tumor invasion. In the present study, we analyzed the expression of
      beta3GnT8 and its product polylactosamine in four human colorectal carcinoma cell
      lines (LS-174T, SW620, SW480 and LoVo) with different metastatic potential. We
      found that the levels of beta3GnT8 and polylactosamine chains were gradually
      increased in the colorectal cancer cell lines in a trend from low to high
      metastatic potential. Notably, a significantly positive relationship between
      beta3GnT8 expression and HG-CD147 was noted in the colorectal cancer cell lines.
      To further investigate their relationships, exogenous beta3GnT8 was introduced
      into the LS-174T cells, while expression of beta3GnT8 was downregulated in the
      LoVo cells. The overexpression of beta3GnT8 in LS-174T cells increased the level
      of HG-CD147. Conversely, downregulation of beta3GnT8 expression in LoVo cells
      significantly decreased the expression of HG-CD147. HG-CD147 is a major carrier
      of beta1,6-branched polylactosamine sugars; therefore, the regulation of
      beta3GnT8 significantly altered the beta1,6-branched polylactosamine structures
      on CD147. Hence, we suggest that beta3GnT8 plays a key role in the metastasis of
      colorectal cancer cells by altering the beta1,6-branched polylactosamine sugars
      of CD147. 

PMID- 24573104
TI  - Brand loyalty, patients and limited generic medicines uptake.
AB  - The sluggish development of European generic drug markets depends heavily on
      demand side factors, and more specifically, patients' and doctors' loyalty to
      branded products. Loyalty to originator drugs, to the point where originator
      prices rise upon generic entry has been described as the 'generics paradox'.
      Originator loyalty can emerge for a plethora of reasons; including costs,
      perceptions about quality and physician advice. We know very little about the
      behavioural underpinnings of brand loyalty from the consumer or patient
      standpoint. This paper attempts to test the extent to which patients are brand
      loyal by drawing upon Spain's 2002 Health Barometer survey as it includes
      questions about consumer acceptance of generics in a country with exceptionally
      low generic uptake and substitution at the time of the study. Our findings
      suggest that at least 13% of the population would not accept generics as
      substitutes to the originator. These results confirm evidence of brand loyalty
      for a minority. Alongside high levels of awareness of generics, we find that low
      cost-sharing levels explain consumer brand loyalty but their impact on acceptance
      of generic substitution is very small. Higher cost-sharing and exempting fewer
      patients from cost-sharing have the potential to encourage generic acceptance. 

PMID- 24573105
TI  - [The throwing shoulder].
AB  - BACKGROUND: During the throwing motion high forces are placed on the athlete's
      shoulder and extreme positions of external rotation and abduction are reached.
      The dynamic and static stabilizers of the glenohumeral joint need to handle a
      delicate balance between shoulder mobility and stability. CAUSES OF INJURY:
      Repetitive forces lead to adaptive osseous, capsular, ligament and muscular
      changes. This should increase external rotation of the shoulder and thus
      initially help to improve performance but ultimately could cause shoulder
      pathologies. For instance, tissue overuse can result in muscular imbalance,
      functional instability and posterior capsular contracture with the development of
      a glenohumeral internal rotation deficit. INJURY PATTERNS: An internal
      impingement is often observed in throwing athletes which can be subdivided into
      the more common posterosuperior type and the rarer anterosuperior type. Typical
      lesions in the throwing shoulder are articular-sided partial rotator cuff tears,
      labrum and biceps tendon lesions and edema, cysts or osteochondral lesions of the
      humeral head or glenoid. DIAGNOSTICS: For an accurate diagnosis it is important
      to include the history, a thorough physical examination and magnetic resonance
      arthrography. The correlation of clinical examination and imaging is critical to
      identify symptomatic lesions. THERAPY: If conservative therapy fails or in cases
      of significant structural damage resulting in clinical symptoms, surgical
      treatment should be considered based on the underlying pathology and carried out
      using established techniques and criteria.

PMID- 24573106
TI  - Current concepts in psoriatic arthritis: pathogenesis and management.
AB  - Psoriatic arthritis occurs in a subset of psoriasis patients and is therefore
      commonly encountered in dermatology practice. Although its exact pathogenesis is
      unknown, psoriatic arthritis is thought to share common mechanisms with psoriatic
      skin symptoms. Innate and adaptive immune responses are abnormally activated in
      psoriasis and may acquire the ability to attack peripheral joints and other sites
      following an environmental trigger (e.g. mechanical stress, trauma, infection) in
      genetically susceptible patients. The increased cardiovascular risk inherent in
      psoriasis appears further enhanced in psoriatic arthritis, likely reflecting the
      overall burden of systemic inflammation contributing to atherogenic processes.
      Basic research and clinical trials have suggested that tumour necrosis factor is
      important in psoriatic arthritis pathophysiology, and accumulating evidence
      suggests that Th17 cells and interleukin-17A may also be important. Basic
      research and clinical trials inform our understanding of psoriatic arthritis
      pathophysiology and, in turn, help dermatologists to make better treatment
      decisions. 

PMID- 24573107
TI  - DFT studies on the mechanism of palladium-catalyzed carbon-silicon cleavage for
      the synthesis of benzosilole derivatives.
AB  - DFT calculations have been carried out to study the detailed mechanism of Pd
      catalyzed intermolecular coupling reactions of 2-silylaryl bromides with alkynes
      via selective cleavage of C(sp(3))-Si bonds. Through our calculations, we found
      that, starting from the alkenylpalladium intermediate derived from oxidative
      addition of the substrate C-Br bond followed by alkyne insertion, there are two
      possible pathways leading to the formation of the benzosilole product.
      Furthermore, these two pathways were found to be competitive. In this paper, we
      will present the detailed mechanistic study and analyze the results we have
      obtained. 

PMID- 24573108
TI  - Commentary on "Angiosome-targeted lower limb revascularization for ischaemic foot
      wounds: systematic review and meta-analysis".

PMID- 24573110
TI  - ROCK1, a novel target of miR-145, promotes glioma cell invasion.
AB  - Malignant glioma is the most common type of cancer in the central nervous system,
      with highly invasive characteristics. The Rho-associated protein kinase (ROCK1)
      has been found to act as key regulator of actin cytoskeleton reorganization, a
      process closely associated with cancer cell invasion. microRNA-145 (miRNA-145)
      has been recently shown to act as a suppressor in several types of tumor,
      including glioma. However, the exact regulatory mechanism by which miR-145
      inhibits glioma still remains to be uncovered. In this study, we report that the
      miR-145 level was significantly reduced in glioma tissues and in the human glioma
      cell lines U87 and U251, as compared to matched adjacent and normal brain
      tissues. We then identified the ROCK1 gene as a novel target of miR-145. The
      expression of ROCK1 was markedly upregulated in glioma tissues, as well as in U87
      and U251 cells. Moreover, miR-145 significantly inhibited ROCK1 protein
      expression in U87 cells. We further show that miR-145 transfection considerably
      reduced the invasive ability of U87 cells, and was accompanied by the
      downregulation of matrix metalloproteinase 2 and 9, an effect which could be
      attenuated by overexpression of ROCK1. In conclusion, the present study suggests
      that miR-145 can inhibit U87 glioma cell invasion, at least partially via
      downregulation of the RhoA/ROCK1 pathway. In conclusion, this is the first study
      to report that ROCK1, as a novel target of miR-145, acts as a positive regulator
      of glioma cell invasion. Therefore, ROCK1 may constitute a promising target for
      glioma treatment. 

PMID- 24573109
TI  - Fluctuation-based imaging of nuclear Rac1 activation by protein oligomerisation.
AB  - Here we describe a fluctuation-based method to quantify how protein
      oligomerisation modulates signalling activity of a multifunctional protein. By
      recording fluorescence lifetime imaging microscopy (FLIM) data of a FRET
      biosensor in a format that enables concomitant phasor and cross Number and
      Brightness (cN&B) analysis, we measure the nuclear dynamics of a Rac1 FRET
      biosensor and assess how Rac1 homo-oligomers (N&B) regulate Rac1 activity (hetero
      oligomerisation with the biosensor affinity reagent, PBD, by FLIM-FRET) or
      interaction with an unknown binding partner (cN&B). The high spatiotemporal
      resolution of this method allowed us to discover that upon DNA damage monomeric
      and active Rac1 in the nucleus is segregated from dimeric and inactive Rac1 in
      the cytoplasm. This reorganisation requires Rac1 GTPase activity and is
      associated with an importin-alpha2 redistribution. Only with this multiplexed
      approach can we assess the oligomeric state a molecular complex must form in
      order to regulate a complex signalling network. 

PMID- 24573111
TI  - Proliferation inhibition and differentiation induction of hepatic cancer stem
      cells by knockdown of BC047440: a potential therapeutic target of stem cell
      treatment for hepatocellular carcinoma.
AB  - Recent findings suggest that clinical hepatocellular carcinoma (HCC) progression
      is driven by hepatic cancer stem cells (HCSCs) through their capacity for self
      renewal, generation of heterogeneous lineages of cancer cells, resistance to
      chemotherapy and their ability to divide limitlessly, which may contribute to the
      failure of existing therapies to consistently eradicate malignant tumors.
      Therefore, HCSC-directed therapeutic approaches might represent strategies to
      improve clinical HCC therapy. In previous studies, we showed that BC047440 was
      found to play a critical role in mediating HCC cell proliferation. The present
      study sought to determine whether BC047440 is involved in maintaining HCSC
      malignant behavior (including proliferation and differentiation). We demonstrated
      that BC047440 expression was markedly upregulated in HCSCs. Furthermore, we
      inhibited BC047440 in HCSCs using short hairpin RNA (shRNA). The effects of
      BC047440 on proliferation and differentiation were investigated. We also analyzed
      the involvement of critical molecular events known to regulate the proliferation
      and the differentiation machinery. Excluding apoptosis-related effects, we found
      that BC047440 inhibition resulted in enhanced cell proliferation through
      enhancing cytoplasmic accumulation of nuclear factor-kappaB (NF-kappaB) with a
      concomitant decrease in the nuclear fraction. BC047440 inhibition also resulted
      in inducing HCSC differentiation into hepatocytes. Furthermore, following
      downregulation of BC047440, the level of hepatocyte nuclear factor 4alpha
      (HNF4alpha) increased. Finally, tumorigenicity suppression following BC047440
      depletion was confirmed in a nude mouse model. In conclusion, our findings
      indicate that BC047440 plays an important role in the proliferation and
      differentiation of HCSCs and may represent a novel therapeutic target for the
      treatment of HCC. 

PMID- 24573112
TI  - C1-esterase-inhibitor for primary graft dysfunction in lung transplantation.
AB  - BACKGROUND: Primary graft dysfunction (PGD) is the most important cause of early
      morbidity and mortality in lung transplantation (LTX) with an incidence of 8% to
      20%. We hypothesized that application of C1-esterase-inhibitor (C1-INH) in LTX
      recipients showing early signs of severe PGD would attenuate the condition.
      METHODS: Starting as of May 2010, all recipients showing a PaO2/FiO2 ratio of
      less than 100 as early sign of PGD at first measurement in the OR were
      immediately treated with C1-INH. Postoperative courses of C1-INH-treated
      recipients were compared with a subgroup of recipients that developed severe PGD
      (PGD3-group) within 72 hours after LTX but did not receive C1-INH. Additionally,
      a third group consisting of all remaining recipients was assembled. RESULTS: A
      total of 275 LTX were performed between May 2010 and September 2012 at our
      center. Among these, 24 patients (8.7%) revealed a first PaO2/FiO2 ratio less
      than 100 and were treated with C1-INH (C1-INH-group). The PGD3-group consisted of
      14 patients; the control cohort consisted of 237 patients. PGD scores were
      significantly higher in the C1-INH-group and PGD3-group as compared with the
      control group at all times postoperatively. ICU stay was longest in the PGD3
      cohort and prolonged in C1-INH patients compared with the control group (29 [2
      70] vs. 9 [2-83] vs. 3 [1-166] days, P=0.002). One-year survival in the PGD3
      cohort was 71.4%, the C1-INH-treated-group had a one-year-survival of 82.5%, the
      control group had the best outcome (95%) (P=0.001). CONCLUSION: Treatment of PGD
      with C1-INH led to acceptable outcome. Although survival in the C1-INH treated
      patients was lower than in the remaining collective, it was as good or better,
      compared with the PGD3 group and as what is internationally regarded as
      reasonable after LTX.

PMID- 24573113
TI  - Outcome and cost analysis of induction immunosuppression with IL2Mab or ATG in
      DCD kidney transplants.
AB  - BACKGROUND: Kidney transplantation from DCD now represents a significant part of
      the overall transplant activity in the UK. Outcome of different induction
      immunosuppression regimes and related cost benefit analysis has been reported by
      very few studies.This is a single centre study on frequency-matched patients who
      received a DCD kidney transplant between August 2007 and August 2009. METHODS:
      Data on 45 patients divided in 2 groups were collected prospectively and analyzed
      retrospectively. Group A (24 patients) received IL2Mab and Group B (21 patients)
      ATG as induction immunosuppression. Patient and graft survival were similar in
      both groups. RESULTS: In the ATG-induced group, there was a significant lower
      rate of DGF, BPAR, and infections requiring readmission.A cost analysis was
      performed including all immunosuppression-related costs, and it has shown
      remarkable savings in the ATG-induced group. CONCLUSION: Considering that the
      number of DCD kidney transplants is destined to rise in the UK, we believe that
      ATG is a valid option to continue optimizing outcomes of DCD kidney transplant.
      In our experience, ATG proved to be safe, effective, and contributed to
      significant cost savings.

PMID- 24573115
TI  - Overcoming primary graft dysfunction after lung transplantation: are we finding
      our way there?

PMID- 24573121
TI  - Development of a novel chiral palladacycle and its application in asymmetric
      hydrophosphination reaction.
AB  - A novel amine ligand, 1-(2,5-dichlorophenyl)-N,N-dimethylethanamine, was
      synthesized from 1-(2,5-dichlorophenyl)ethanone via a three step synthetic route.
      Direct ortho-palladation of the amine ligand with Pd(OAc)(2) gave the racemic
      dimeric complex in high yield. This racemic palladacycle was efficiently resolved
      through the formation of its (S)-prolinato derivatives. The resulting
      diastereomeric complexes were separated efficiently by column chromatography. In
      the solid state, the structure and absolute configuration of the two optically
      resolved palladium complexes were determined by single crystal X-ray
      crystallography. In solution, their absolute conformations were also investigated
      by the 2D (1)H-(1)H rotating frame nuclear Overhauser enhancement (ROESY) NMR
      spectroscopy. Both (R,R) and (S,S)-di-MU-chloro dimeric palladium complexes could
      be obtained chemoselectively by treating the corresponding prolinato derivatives
      with dilute hydrochloric acid. The amine auxiliary could be subsequently removed
      from the palladium center by treatment with concentrated hydrochloric acid. The
      enantiomerically pure palladacycle was used to promote the asymmetric
      hydrophosphination reaction between diphenylphosphine and dimethyl
      acetylenedicarboxylate. The (31)P{(1)H} NMR spectroscopy indicated that only one
      stereo-isomeric product was formed. 

PMID- 24573114
TI  - Health literacy of living kidney donors and kidney transplant recipients.
AB  - BACKGROUND: Health literacy (HL) may be a mediator for known socioeconomic and
      racial disparities in living kidney donation. METHODS: We evaluated the
      associations of patient and demographic characteristics with HL in living kidney
      donors (LD), living donor kidney transplant recipients (LDR), and deceased donor
      recipients (DDR) in a single-center retrospective review of patients undergoing
      kidney donation or transplantation from September 2010 to July 2012. HL and
      demographic data were collected. HL was assessed via the Short Literacy Survey
      (SLS) comprising three self-reported screening questions scored using the five
      point Likert scale (low, moderate, high). Chi-square and logistic regression were
      used to test factors associated with lower HL. RESULTS: The sample included 360
      adults (105 LD, 103 LDR, and 152 DDR; 46+/-14 years; 70% white; 56% male; 14+/-3
      years of education). HL scores were skewed (49% high, 41% moderate, and 10% low).
      The distribution of HL categories differed significantly among groups (P=0.019).
      After controlling for age, race, sex, education, and a race-education interaction
      term, DDR was more likely to have moderate or low HL than LDR (OR, 1.911; 95% CI,
      1.096-3.332; P=0.022). CONCLUSION: Overall, living donors had high HL. The
      distribution of low, moderate, and high HL differed significantly between LD,
      DDR, and LDR. DDR had a higher likelihood of having low HL than LDR. Screening
      kidney transplant candidates and donors for lower HL may identify barriers to
      living donation. Future interventions addressing HL may be important to increase
      living donation and reduce disparities.

PMID- 24573122
TI  - Antioxidant supplementation attenuates oxidative stress in patients undergoing
      coronary artery bypass graft surgery.
AB  - Ischemia-reperfusion has been reported to be associated with augmented oxidative
      stress in the course of surgery, which might be causally involved in the onset of
      atrial fibrillation (AF), the most common arrhythmia after cardiac surgery. We
      hypothesized that supplementation of antioxidants and n-3 polyunsaturated fatty
      acids (n-3 PUFAs) might lower the incidence of AF following coronary artery
      bypass graft (CABG) surgery. In the present study, by monitoring oxidative stress
      in the course of CABG surgery, we analyzed the efficacy of vitamins (ascorbic
      acid and alpha-tocopherol) and/or n-3 PUFAs (eicosapentaenoic acid and
      docosahexaenoic acid). Subjects (n = 75) were divided into 4 subgroups: control,
      vitamins, n-3 PUFAs, and a combination of vitamins and n-3 PUFAs. Fluorescent
      techniques were used to measure the antioxidative capacity, i.e. ability to
      inhibit oxidation. Total peroxides, endogenous peroxidase activity, and
      antibodies against oxidized LDL (oLAb) were used as serum oxidative stress
      biomarkers. Post-operative increase in oxidative stress was associated with the
      consumption of antioxidants and a simultaneous onset of AF. This was confirmed
      through an increased peroxide level and a decreased oLAb titer in control and n-3
      PUFAs groups, indicating the binding of antibodies to oxidative modified
      epitopes. In both subgroups that were supplemented with vitamins, total peroxides
      decreased, and the maintenance of a constant IgG antibody titer was facilitated.
      However, treatment with vitamins or n-3 PUFAs was inefficient with respect to AF
      onset and its duration. We conclude that the administration of vitamins
      attenuates post-operative oxidative stress in the course of CABG surgery. 

PMID- 24573123
TI  - State of the art in temporal bone malignancies.
AB  - PURPOSE OF REVIEW: To discuss the histological variants, tumor staging, work up
      and the latest trends in the treatment of malignancies of the temporal bone.
      RECENT FINDINGS: Because of the rarity of this subset of tumors, there has been
      no serious attempt to study tumor histologies of the temporal bone other than the
      squamous cell carcinomas (SCCs). The modified Pittsburgh tumor staging, though
      popularly used, was primarily developed only for SCC of the external auditory
      canal. Recent studies have shown that this staging is not without faults. There
      is also divergence of opinions regarding the surgical procedures to be adopted in
      treating temporal bone carcinomas. Moreover, the role of radiotherapy and
      chemotherapy has not been clearly defined. SUMMARY: In this review, we analyzed
      all the histological varieties of tumors that can arise from the temporal bone
      and classified them. The merits and demerits of the modified Pittsburgh tumor
      staging has been discussed outlining the need for further refining this system.
      The surgical approaches and their applications with respect to the extent of the
      tumor have been defined. The role of parotidectomy, neck dissection and adjuvant
      radiotherapy has been discussed.

PMID- 24573124
TI  - Role of multiple free flaps in head and neck reconstruction.
AB  - PURPOSE OF REVIEW: The benefit of using multiple simultaneous free flaps for
      postablative extensive composite head and neck reconstruction has gradually
      become increasingly accepted worldwide, with recent case series being reported
      from several continents. This review summarizes the cogent conclusions that can
      be drawn from this growing international experience. RECENT FINDINGS: Running
      themes include: firstly, that careful organization of the operation is critical
      to expediency to the extent that double and single free flap reconstructions are
      not greatly different in duration; secondly, that the functional results of
      double free flap reconstructions are generally better than single free flap
      reconstructions when the defect is appropriately extensive; and thirdly, that
      there remains a lack of consensus regarding which patients would and would not
      benefit from a double free flap approach from a survival perspective. SUMMARY:
      Local audit should guide local practice for when double free flap reconstructions
      are or are not appropriate, as survival data are greatly variable internationally
      because of the differences in treatment, margins status for resections and,
      amongst other factors, cause and aggression of tumors. This is especially the
      case for the most infiltrative malignancies that mandate extensive composite
      resections for which a double free flap procedure would likely provide the best
      long-term functional and aesthetic results.

PMID- 24573125
TI  - The link between allergy and Meniere's disease.
AB  - PURPOSE OF REVIEW: To examine evidence supporting the association of allergy and
      Meniere's disease. RECENT FINDINGS: Animal studies have shown evidence that a
      provoked systemic immune challenge can result in an allergic reaction within the
      inner ear, whereas premedication with leukotriene antagonists can prevent the
      development of endolymphatic hydrops. In human subjects, further data support a
      heightened allergic response in patients with Meniere's disease, whereas
      pharmacological treatments that target histamine receptors help to control
      vertiginous symptoms. However, the relationship of migraine with a history of
      allergy and Meniere's disease may confound this association. SUMMARY: Although
      the evidence of a causal association between allergy and Meniere's disease is
      inconclusive, the inclusion of allergy control as part of the treatment plan for
      Meniere's disease is low risk to the patient and should be considered for
      patients with indications that include history of seasonal or food allergy,
      childhood or family history of allergy, bilateral Meniere's symptoms, or a
      development of symptoms within a short time after exposure of food or inhaled
      allergen.

PMID- 24573126
TI  - Current understanding of allergic fungal rhinosinusitis and treatment
      implications.
AB  - PURPOSE OF REVIEW: The pathophysiology of allergic fungal rhinosinusitis (AFRS)
      is not fully understood and is in constant evolution. Although initial theories
      favored an immunoglobulin E-mediated immune response to fungal antigens as having
      a primary role in the immunopathologic process of AFRS, the purpose of this
      review is to highlight recent studies that suggest a more complex, epithelial
      cell-driven immune response being central to the pathophysiology of the disease.
      Treatment implications are considered. RECENT FINDINGS: Recent studies
      demonstrate a central role of cytokines derived from respiratory epithelial
      cells, including interleukin (IL)-25, IL-33, and thymic stromal lymphopoietin, in
      the orchestration of both innate and adaptive T helper 2 immune responses that
      are important components of the immunopathology of chronic rhinosinusitis with
      nasal polyposis and AFRS. In addition, the robust Th2 adaptive response may be
      mediated by both fungal antigens and Staphylococcus aureus superantigens.
      SUMMARY: Given the evolving understanding of AFRS pathophysiology, management
      continues to maintain a broad focus on minimizing the burden of the inflammatory
      trigger(s) and suppressing the inflammatory cascade. This is primarily
      accomplished through surgery and corticosteroid therapy. Immunotherapy,
      antimicrobial therapy, and other immunomodulatory medications may help mediate
      the disease process as well.

PMID- 24573127
TI  - Time to die!

PMID- 24573128
TI  - A simulation of T-wave alternans vectocardiographic representation performed by
      changing the ventricular heart cells action potential duration.
AB  - The presence of T wave alternans (TWA) in the surface ECG signals has been
      recognized as a marker of electrical instability, and is hypothesized to be
      related to patients at increased risk for ventricular arrhythmias. In this paper
      we present a TWA simulation study. The TWA phenomenon was simulated by changing
      the duration of the ventricular heart cells action potential. The magnitude was
      calculated in the surface ECG with the use of the time domain method. The
      spatially concordant TWA, where during one heart beat all ventricular cells
      display a short-duration action potential and during the next beat they exhibit a
      long-duration action potential, as well as the discordant TWA, where at least one
      region is out of phase, was simulated. The vectocardiographic representation was
      employed. The obtained results showed a high level of T-loop pattern and location
      disturbances connected to the discordant TWA simulation in contrast to the
      concordant one. This result may be explained by the spatial heterogeneity of the
      ventricular repolarization process, which could be higher for the discordant TWA
      than for the concordant TWA.

PMID- 24573129
TI  - BiOSS: A system for biomedical ontology selection.
AB  - In biomedical informatics, ontologies are considered a key technology for
      annotating, retrieving and sharing the huge volume of publicly available data.
      Due to the increasing amount, complexity and variety of existing biomedical
      ontologies, choosing the ones to be used in a semantic annotation problem or to
      design a specific application is a difficult task. As a consequence, the design
      of approaches and tools addressed to facilitate the selection of biomedical
      ontologies is becoming a priority. In this paper we present BiOSS, a novel system
      for the selection of biomedical ontologies. BiOSS evaluates the adequacy of an
      ontology to a given domain according to three different criteria: (1) the extent
      to which the ontology covers the domain; (2) the semantic richness of the
      ontology in the domain; (3) the popularity of the ontology in the biomedical
      community. BiOSS has been applied to 5 representative problems of ontology
      selection. It also has been compared to existing methods and tools. Results are
      promising and show the usefulness of BiOSS to solve real-world ontology selection
      problems. BiOSS is openly available both as a web tool and a web service.

PMID- 24573130
TI  - Monitoring population sodium intake using spot urine samples: validation in a New
      Zealand population.
AB  - Although 24-h urine collection is widely considered the 'gold standard' for
      estimation of population sodium intake, spot urine collection is increasingly
      used as a convenient and affordable alternative. We used four published formulae
      to convert spot urine sodium into estimates of 24-h sodium excretion in order to
      establish which (if any) formula would be suitable for use in the New Zealand
      population. A convenience sample of 101 healthy volunteers provided two spot
      urine samples and a 24-h urine collection. Two formulae (one proposed by the Pan
      American Health Organisation (PAHO) and one derived from INTERSALT data) were
      most accurate, and provided estimates of key population indicators (mean, range
      and proportion above nutrient reference values) that were close to those of the
      measured 24-h urine excretion. Estimates using these formula were in closer
      agreement with 24-h excretion than the other formulae estimates using the Bland
      Altman method. We conclude that spot urine sampling is a suitable alternative to
      24-h urine collection in population surveys when spot urine sodium results are
      converted into estimates of 24-h sodium excretion using either the PAHO or
      INTERSALT formulae. However spot urine is a poor predictor of 24-h urinary sodium
      excretion for individual assessment. 

PMID- 24573131
TI  - Prevalence and characteristics of hypertension in mainland Chinese adults over
      decades: a systematic review.
AB  - Hypertension is considered to be the leading risk factor for cardiovascular
      mortality and accounts for a large proportion of premature deaths in China. An
      empirical understanding of the pattern of disease burden, such as reliable
      information about the trend and prevalence of hypertension, is essential in
      developing effective prevention and control strategies and is also important in
      the decision-making and planning processes of health. However, there are limited
      comprehensive reviews or nationwide studies that reveal the current burden of
      hypertension in China. This review is to systematically evaluate hypertension
      prevalence and determinants as well as its awareness, treatment and control over
      decades in China. A systematic search was performed for epidemiological studies
      on hypertension, published between 1982 and January 2013. MeSH major topic terms
      'hypertension' and 'prevalence' and 'China' were used in the search. Data on
      hypertension prevalence, determinants and awareness, as well as its treatment and
      control, were extracted and compared. Sixty articles were included for data
      extraction. The prevalence reported in the studies varied from 7.17 to 51.2%.
      Awareness, treatment and control rates also varied regionally. Except in the
      central region of China, where a declining trend in hypertension prevalence was
      witnessed, a rising trend in hypertension prevalence over time could still be
      observed in other parts of China. Higher hypertension prevalence was found among
      men and in the urban population, whereas lower prevalence was found in the
      southern region. Hypertension awareness and treatment rate varied extensively,
      with a low control rate, nationwide. 

PMID- 24573132
TI  - Parental history of hypertension and dietary intakes in early adolescent
      offspring: a population-based study.
AB  - We investigated the cross-sectional association between parental history of
      hypertension and dietary intakes among early adolescent schoolchildren. A total
      of 1845 participants aged 12 years had complete data on diet and parental medical
      history, and thus they were included in the final analyses. Dietary data were
      assessed from validated semi-quantitative food-frequency questionnaires. Parents
      completed questionnaires about their medical conditions. Cases where the
      biological mother and/or father had hypertension were classified as positive
      parental history of hypertension. After multivariable adjustment, participants
      with positive versus negative parental history of hypertension had 33% greater
      likelihood of consuming soft drinks ?1 per week. Boys with a parental history
      versus boys without a parental history of hypertension consumed more energy
      dense, nutrient-poor foods: 379.4 g per day and 318.0 g per day, respectively,
      P=0.02. Girls with a positive versus a negative parental history consumed more
      vegetables: 164.1 versus 142.6 g per day, P=0.01. Significant associations were
      not observed between those with and those without a positive parental history in
      mean dietary intakes of carbohydrates, fats, sugars and sodium. Children with a
      positive parental history of hypertension were 67% more likely to simultaneously
      engage in three unhealthy lifestyle behaviors (excessive recreational screen
      viewing, high consumption of snacks and and high consumption of soft drinks).
      Parental hypertension was associated with unhealthy dietary behaviors among
      offspring, including higher consumption of soft drinks and energy-dense, nutrient
      poor foods. 

PMID- 24573135
TI  - Clinical strategies for controlling costs and improving quality in the primary
      care of low back pain.
AB  - Back pain is a pervasive problem which ranks only behind cold symptoms as a
      reason for all physician visits. Among persons with back pain lasting at least
      two weeks, 85% will seek the care of a health professional. These patients obtain
      care from primary care physicians (Family Medicine, Internal Medicine, and
      Osteopathic physicians), but also see a variety of specialists, including
      physiatrists, rheumatologists, orthopedic surgeons, and neurosurgeons. Since any
      of these specialties may evaluate patients early in their course, it is important
      to adopt a systematic and rational early approach to back pain. This discussion
      emphasizes recent data suggesting that such an approach would include a
      parsimonious diagnostic evaluation, careful attention to patients' concerns, and
      careful choice of proven effective treatments. Specifically, we propose five
      strategies that may help to reduce costs of care while maintaining quality:1.
      Avoid premature or unnecessary diagnostic tests.2. Avoid patient deactivation.3.
      Avoid ineffective or unproven remedies.4. Prescribe effective therapy in a cost
      conscious manner, and5. Emphasize lifestyle changes and patient self-efficacy. 

PMID- 24573136
TI  - Spondylolisthesis.

PMID- 24573133
TI  - Unmasking masked hypertension: prevalence, clinical implications, diagnosis,
      correlates and future directions.
AB  - 'Masked hypertension' is defined as having non-elevated clinic blood pressure
      (BP) with elevated out-of-clinic average BP, typically determined by ambulatory
      BP monitoring. Approximately 15-30% of adults with non-elevated clinic BP have
      masked hypertension. Masked hypertension is associated with increased risks of
      cardiovascular morbidity and mortality compared with sustained normotension (non
      elevated clinic and ambulatory BP), which is similar to or approaching the risk
      associated with sustained hypertension (elevated clinic and ambulatory BP). The
      confluence of increased cardiovascular risk and a failure to be diagnosed by the
      conventional approach of clinic BP measurement makes masked hypertension a
      significant public health concern. However, many important questions remain.
      First, the definition of masked hypertension varies across studies. Further, the
      best approach in the clinical setting to exclude masked hypertension also remains
      unknown. It is unclear whether home BP monitoring is an adequate substitute for
      ambulatory BP monitoring in identifying masked hypertension. Few studies have
      examined the mechanistic pathways that may explain masked hypertension. Finally,
      scarce data are available on the best approach to treating individuals with
      masked hypertension. Herein, we review the current literature on masked
      hypertension including definition, prevalence, clinical implications, special
      patient populations, correlates, issues related to diagnosis, treatment and areas
      for future research. 

PMID- 24573134
TI  - Interferon beta protects against lethal endotoxic and septic shock through SIRT1
      upregulation.
AB  - Lipopolysaccharide (LPS), an endotoxin derived from gram-negative bacteria,
      promotes the secretion of proinflammatory cytokines and mediates endotoxemia
      through activation of mitogen activated protein kinases, NF-kappaB, and
      interferon regulatory factor-3. Silent information regulator transcript-1
      (SIRT1), an NAD-dependent deacetylase, mediates NF-kappaB deacetylation, and
      inhibits its function. SIRT1 may affect LPS-mediated signaling pathways and
      endotoxemia. Here we demonstrate that SIRT1 blocks LPS-induced secretion of
      interleukin 6 and tumor necrosis factor alpha in murine macrophages, and protects
      against lethal endotoxic and septic shock in mice. We also demonstrate that
      interferon beta increases SIRT1 expression by activating the Janus kinase--signal
      transducer and activator of transcription (JAK-STAT) pathway in mouse bone marrow
      derived macrophages. In vivo treatment of interferon beta protects against lethal
      endotoxic and septic shock, which is abrogated by infection with dominant
      negative SIRT1-expressing adenovirus. Our work suggests that both SIRT1 and SIRT1
      inducing cytokines are useful targets for treating patients with sepsis.

PMID- 24573138
TI  - Resistance training for rehabilitation of disability secondary to low back pain.
AB  - Low back pain (LBP) is the number-one cause of disability of individuals under 40
      years of age. The cost to society both in medical expense and loss of
      productivity is billions of dollars annually.1,2 The etiology of both acute and
      more persistent LBP is multifactorial, but torso weakness is considered a
      contributing factor. It is well documented that improved strength, as well as
      general conditioning, improve the odds of successful return to work.2-7 For these
      reasons, resistance training is often prescribed for the prevention and
      rehabilitation of disability secondary to LBP.The purpose of this article is to
      review current literature regarding resistance training for rehabilitation of
      LBP. Trunk strengthening will be reviewed in more detail and general principles
      for extremity resistance training will be reviewed as well. 

PMID- 24573137
TI  - Evaluation and conservative management of spondylolisthesis.
AB  - Plain x-rays of the lumbar spine are not helpful in diagnosing most known causes
      of low back pain but can reveal structural changes such as disc space narrowing,
      scoliosis, lumbarization or sacralization, spondylolysis, and spondylolisthesis.
      Spondylolisthesis is defined as the forward displacement of one vertebrae upon
      another, usually at the L5-S1 level, but also occurring at L4-5. For
      spondylolisthesis to occur there must be an anatomical change in the structures
      which normally resist the anterior displacement of one vertebrae upon the other.
      Forward slippage is resisted by the bony block of the posterior facets, by the
      intact neural arch and pedicle, by normal bone plasticity preventing stretch of
      the pedicle, and by the intervertebral disc bonding the vertebral bodies
      together.1 The degree of vertebral body anterior displacement is rated from 1-4
      depending upon the severity of the slip.2 Five major categories have been
      proposed for the classification of spondylolisthesis.3 Clinically, the type most
      often seen is a defect in the pars interarticularis of L5 with resultant slippage
      of L5 on S1. This is known as isthmic spondylolisthesis. The other commonly seen
      type of spondylolisthesis is degenerative, arising from the remodeling of the
      facet joints so that bony opposition to resist anterior displacement of one
      vertebrae upon another no longer exists. Degenerative spondylolisthesis most
      commonly occurs at the L4-5 level in women over the age of 40. Surgical
      intervention for treatment of spondylolisthesis is well documented,4-6 but
      literature regarding conservative management is scarce. The purpose of this
      article is to present an evaluation and treatment approach which has been found
      by the author to be clinically effective for patients presenting with symptomatic
      grade I or II isthmic or degenerative spondylolisthesis.Documented conservative
      treatment for spondylolisthesis includes instruction in exercise and body
      mechanics, the use of back supports including antilordotic orthoses, and job
      modifications. Magora7 recommends strengthening of the abdominals and paraspinal
      muscles, especially in the thoracic area, as well as occupational modifications
      and instruction in body mechanics, deep-heat therapy, avoidance of maximal
      forward flexion of the lumbar spine, and in severe cases, bed rest. He recommends
      three to four months as the minimal trial period for conservative treatment.
      Gramse et al.8 and Sinaki et al.9 compared two types of exercise programs over a
      three-year period for patients with symptomatic spondylolisthesis. Patients were
      divided into two groups with one group performing a flexion routine consisting of
      abdominal curl-ups, posterior pelvic tilts, and seated trunk flexion; a second
      group was instructed in extensor strengthening exercises performed in prone
      lying. The authors found that patients treated with the flexion exercise program
      were less likely to require the use of back supports, require job modification,
      or limit their activities because of pain. At three-year follow-up only 19% of
      the flexion group had moderate or severe pain compared to 67% of the patients in
      the extension group.9 Gramse et al.8 and Sinaki et al.9 did not describe how they
      determined that the spondylolisthesis was indeed symptomatic. Bell et al.10
      reported 100% success with the use of an antilordotic orthosis in 28 children
      (mean age 11.4 years) with grade I and grade II isthmic spondylolisthesis. Other
      authors have been less enthusiastic about the use of corsets and braces.7,11. 

PMID- 24573139
TI  - An overview of functional progressions in the rehabilitation of low back
      patients.
AB  - Low back pain is one of the most common dysfunctions seen by health care
      professionals. Eighty percent of the population will suffer from low back pain in
      their adult life.1-4 Accordingly, this societal problem has taken its toll via
      missed days of work and the adverse economic impact that results.3-9The good news
      is that most people with low back pain improve within a short period of time.1,9
      11 Acute attacks of back pain and sciatica can last up to two weeks with chronic
      attacks persisting for more than three months.10 Vukmir reported that 74.2% of
      patients with low back pain improved within one month, 87.3% within three months,
      and 92.6% within six months.1 Additional good news is the fact that surgery is
      the appropriate solution for only a small percentage of the patients with low
      back pain.12,13 Saal and Saal report that nonoperative treatment for lumbar
      disorders, including intervertebral disc dysfunction prove most successful.13
      Weber, in a landmark study, reported that patients who received surgery for
      lumbar disc herniations showed statistically better results at the one-year
      follow-up examination. However, at the four-year follow-up, there were no
      statistically significant differences in how patients who received surgery
      compared to the patients who did not receive surgery.14On a less positive note,
      people who suffer an episode of low back pain, have a greater chance of
      developing future episodes.10,15 Those patients who develop repeated episodes of
      low back pain and those patients who do not improve spontaneously over a short
      period of time can fall into the group known as chronic low back pain. This group
      creates a major drain on our economic resources and leads to a large number of
      people who are deemed disabled.1,7,8,12 Therefore, if the health care community
      is unable to cure all types of low back pain, keeping patients with low back pain
      functional should be of prime importance. Through the performance of functional
      activities, such as activities of daily living and working, the societal drain
      caused by low back pain, would hopefully decrease. 

PMID- 24573140
TI  - A program of functional progression for low back patients.

PMID- 24573141
TI  - Roles and responsibilities of team members in the functional capacity evaluation
      and rehabilitation of the injured worker.

PMID- 24573142
TI  - Cancer rehabilitation approaches to neurologic pain syndromes in malignancy.
AB  - Pain is a common symptom in cancer patients. Thirty to fifty percent of patients
      will experience pain while undergoing cancer treatment, and 70 to 90% of patients
      with advanced disease report pain.1-7 In addition, greater than 50% of patients
      state their pain is incompletely controlled. In part, this is due to the
      difficulty physicians have in accurately assessing the patient's level of pain
      and response to treatment, as well as utilizing a treatment approach that is
      agreeable to the patient. It is common that patients underreport the severity of
      the pain that they are experiencing, as well as their inability to achieve pain
      control. There are many possible reasons for this, including their wish to
      appease the physician; the fear of confirming progression of their disease by
      admitting to having increased pain; and the concern of possible narcotic
      addiction. To address these problems, the World Health Organization, the American
      Pain Society, and the American Society of Clinical Oncology's Ad Hoc Committee on
      Cancer Pain have published guidelines for assessing and treating pain.8-10Pain is
      one of the most disabling conditions experienced by cancer patients.7,11-14 This
      disabling effect is exacerbated by the patient's fear of the loss of control of
      both the ability to regulate his/her pain and loss of control of his physical
      mobility due to the pain. Therefore, it affects the patient both physically and
      emotionally and further compromises the ability of the patient and family to deal
      with the disease.The perceived intensity of the pain as well as the level of
      disability experienced by the patient can be influenced by many variables such as
      family support and cultural background of the patient. These influences in the
      patient's life can magnify or diminish his/her perception of pain and disability.
      Therefore, in the same way that patients tolerate pain differently, the treatment
      approach must to some extent be appropriately individualized, periodically
      reviewed, and frequently altered to change with the needs of the patient. This is
      one reason why those involved with cancer rehabilitation use an individualized
      interdisciplinary approach to the patients' needs, including pain control. In
      addition to the traditional use of analgesics, chemotherapy, radiation therapy,
      surgery, and nerve blocks to palliate pain, cancer rehabilitation employs a wide
      range of other modalities, both physical and cognitive behavioral, in its
      treatment approach. Physical and occupational therapy utilize positioning,
      strengthening, transcutaneous electrical nerve stimulation (TENS), and other
      electrical stimulation modalities, orthotics, and other assistive devices to
      alleviate pain and maximize function. In addition, psychological support in its
      various forms, with both patient and family counseling, affords better handling
      of the disease. In some cases biofeedback and/or hypnosis can be utilized as an
      adjunct to pain control. Since the pathophysiology of cancer pain and its
      pharmacologic, surgical, and radiation treatments were dealt with in a previous
      issue, they will not be addressed further. This article will focus primarily on
      the more unique aspects of cancer rehabilitation, and the physical,
      nonpharmacologic, and behavioral approaches to pain management that practitioners
      commonly use in relation to neurological pain syndromes in cancer. 

PMID- 24573143
TI  - Thoracic segmental flexion during cervical forward bending.
AB  - The purpose of this study was to assess the amount of thoracic segmental flexion
      associated with cervical forward bending. Twenty-four healthy men and women
      between the ages of 21-29, with no past or present cervical or thoracic
      dysfunction, participated. Spinal segmental mobility in the thoracic region was
      measured in the neutral sitting position and sitting with the cervical spine in
      the forward bent position. Mobility was measured by the Faro Metrecom Skeletal
      Analysis System. The Faro Metrecom is an external measuring device that records
      each individual spinal segment's position within the body. Descriptive statistics
      were used to describe the position of the thoracic segments when the cervical
      region was in the neutral and in the forward bent positions. Additionally,
      intrarater reliability, .83 and .76, and interrater, .72, were analyzed for the
      thoracic segments in the neutral position. The results show that with cervical
      flexion there was thoracic segmental flexion. Segments T1-4 demonstrated forward
      bending ranging from 2.88-4.42 degrees . The greatest amount of flexion occurred
      at T2, 4.42 degrees, and T3, 4.19 degrees. Below T4 no pattern was noted. The
      results indicate that upper-thoracic segmental flexion occurs during cervical
      forward bending.During evaluation and treatment of patients with cervical
      dysfunction physical therapists routinely evaluate spinal segmental mobility. It
      is clear to clinicians that cervical segmental mobility is important to cervical
      range of motion. What it not clear is the role of thoracic segmental mobility in
      cervical range of motion. Physical therapists frequently evaluate and treat the
      thoracic region when patients have cervical dysfunction. Therefore, the purpose
      of this study was to assess the amount of thoracic segmental flexion associated
      with cervical forward bending.Since the early 1970s when the concept of joint
      mobilization was brought to American physical therapists, interest in spinal
      segmental motion has increased. Though interest in this area exists, there is a
      scarcity ofresearch documenting normal and abnormal spinal segmental mobility.
      Additionally, most of the studies on spinal segmental mobility have been
      conducted on cadavers or through radiographic methods.Lysell studied
      intersegmental movements of the cervical spine using autopsy specimens. Steel
      balls were placed in fixed points on each vertebrae and then a three-dimensional
      radiographic examination was used to measure movements of these points during
      cervical range of motion.1 Ball and Meijers studied cervical mobility using fresh
      cadaveric cervical spinal specimens. In this study steel pins were inserted into
      the cervical bodies and serial x-rays were taken.2 Panjabi, Dvorak, and Duranceau
      studied upper-cervical spine mobility using fresh cadaveric whole cervical spine
      specimens and steel balls. Their specimens were set into a quick-setting epoxy
      material to help align the centers of C2 and C7, thereby providing fixation.3
      Yamamoto et al. studied three-dimensional movements of the lumbar spine and
      lumbosacral joint. They used fresh cadaveric whole lumbar spine specimens
      analyzing from L1 to the sacrum.4 Robert studied intervertebral motion of the
      whole spine. This was performed with cadavers as the segmental excursions were
      determined from a point at the inferior surface of the vertebrae to the tip of
      the spinous process.5Three separate noncadaveric studies were conducted by
      Penning,6 Felding7 and Moll and Wright.8 Penning studied normal movements of the
      cervical spine by superimposing two x-ray films representing the cervical spine
      in the end positions (i.e., flexion and extension). Fielding studied normal and
      abnormal motion of the cervical spine from C2 and C7 using cineroentgenography;
      roentgenograms were taken while the subjects were moving. Moll and Wright studied
      normal range of spinal mobility using live subjects with markers on the skin.
      When the subjects moved the separation of the skin markers was recorded.The above
      studies used procedures that are not convenient for use during clinical sessions.
      Additionally, the above studies did not evaluate thoracic mobility in relation to
      cervical motion.In the textbook, Common Vertebral joint Problems,9 Grieve
      presents a complete discussion of vertebral motion. This section is highly
      referenced as it pertains to segmental spinal mobility.9 White and Panjabi are
      the most frequently cited source on spinal segmental mobility.10,11 They reported
      flexion/extension degrees of motion for the thoracic segments. The ranges of the
      motion and the "representative angle" (most likely the mean angle) in degrees for
      each thoracic segment are T1-T5 2-5 (4); T6 2-7 (5); T7-T9 3-8 (6); T10 4-14 (9);
      and T11-T12 6-20 (12). However, they did not state how their estimated range and
      "representative angle" in degrees of segmental spinal mobility were
      measured.10,11 Valencia in the book Physical Therapy of the Cervical and Thoracic
      Spine states similar motion for the thoracic segments.12The upper-thoracic spine,
      T1-T6, has been related to the cervical region anatomically. The upper-thoracic
      facet joints are orientated like the cervical facet joints and have a similar
      pattern of movement.11,13 Additionally, the caudal attachment of many cervical
      muscles is in the thoracic region.13. 

PMID- 24573145
TI  - Annual index 1993.

PMID- 24573144
TI  - ??? Fce-wts-wh-wce-ffd-wc ???

PMID- 24573147
TI  - From the editor.

PMID- 24573148
TI  - Low back pain.
AB  - Why do so many patients opt for a surgical solution to lumbosacral (L-S)
      radicular pain? A rhetoric as well as specific question.Recently a Big Ten coach
      underwent the scalpel for the third time in two years. "Pain" not masochism was
      his response when questioned by the press, "Why the knife?"Most physicians and
      patients equate the severity of L-S radicular pain with the seriousness of the
      disc derangement.This is not so!Most physicians are aware that radicular pain is
      inversely proportional to the weakness associated with L-S disc herniation or
      extrusion. The natural history is a general remission of pain with a little
      exercise, perhaps some medication, and mostly Mother Nature.A sudden cessation of
      pain suggests a "dead" root and significant weakness. Unfortunate? Not
      necessarily.Electrodiagnostic studies can demonstrate a L-S radiculopathy within
      two weeks of onset and after one week can differentiate neurapraxic (reversible)
      weakness from permanent weakness.In both instances surgery is not the treatment
      of choice. In the first instance a conduction block at this inflamed nerve root
      is the problem and in the second scenario the weakness is generally not
      reversible with surgery (in fact the operation could be blamed).Nonradicular back
      pain needs a physiatric evaluation and management program.Patients should be
      reassured in all situations that most people "get over" acute back pain
      (including radicular) with minimal residuals if they are patient and
      educable!After all, rehabilitation is essentially teaching and patient learning.
      All patients with low back pain need thorough grounding in anatomy and physiology
      of the low back and biomechanics of lifting, in order to fend off advice of well
      meaning friends, relatives, or even other "health" professionals.A recent study
      announced 10 times more lumbar laminectomies are done in the United States than
      in Europe. To reduce this number, I suggest all second opinions for this major
      (e.g., Discectomy) lumbar assault be given by a nonsurgeon who understands back
      problems (i.e., a physiatrist).Isn't this essentially the same as a
      gastroenterologist presenting a second opinion for management of a gastric ulcer
      medical versus surgical?A physiatrist would provide a second opinion instead of a
      seconding opinion. 

PMID- 24573149
TI  - New p-tolylimido rhenium(V) complexes with carboxylate-based ligands: synthesis,
      structures and their catalytic potential in oxidations with peroxides.
AB  - Novel p-tolylimido rhenium(v) complexes trans-(Cl,Cl)-[Re(p-NC6H4CH3)Cl2(pyz-2
      COO)(PPh3)].MeCN (1), trans-(Cl,Cl)-[Re(p-NC6H4CH3)Cl2(pyz-2-COO)(PPh3)] (2),
      trans-(Br,Br)-[Re(p-NC6H4CH3)Br2(pyz-2-COO)(PPh3)] (3), cis-(Cl,Cl)-[Re(p
      NC6H4CH3)Cl2(ind-3-COO)(PPh3)].2MeOH (4), 2[Re(p-NC6H4CH3)Cl2(ind-3
      COO)(PPh3)].MeCN (5), 2[Re(p-NC6H4CH3)Br2(ind-3-COO)(PPh3)].MeOH (6) and 2[Re(p
      NC6H4CH3)Br2(ind-3-COO)(PPh3)].MeCN (7) were obtained in the reactions of [Re(p
      NC6H4CH3)X3(PPh3)2] (X = Cl, Br) with pyrazine-2-carboxylic (pyz-2-COOH or PCA)
      and indazole-3-carboxylic (ind-3-COOH) acids. The compounds were identified by
      elemental analysis, IR, (1)H, (13)C and (31)P NMR spectroscopy and X-ray
      crystallography. To get a deeper understanding of the structural and bonding
      properties of the imido rhenium(v) complexes, calculations at the DFT level were
      undertaken for trans-(Cl,Cl)-[Re(p-NC6H4CH3)Cl2(pyz-2-COO)(PPh3)] and cis-(Cl,Cl)
      [Re(p-NC6H4CH3)Cl2(ind-3-COO)(PPh3)]. Complexes 1, 3, 4 and 6 exhibited high
      catalytic activity in oxidation of alkanes with H2O2 and tert-butyl hydroperoxide
      (TBHP) and of alcohols with TBHP. The selectivity parameters measured in the
      reactions with linear and branched alkanes indicated that the processes with H2O2
      or TBHP proceed with the participation of hydroxyl or tert-butoxyl radicals,
      respectively. The composition of isomers from oxygenation of methylcyclohexane
      corresponds to the existence of some steric hindrance around the reaction
      centers. 

PMID- 24573150
TI  - Expression of the lysyl oxidase propeptide in hepatocellular carcinoma and its
      clinical relevance.
AB  - Lysyl oxidase is an important extracellular matrix remodeling enzyme and plays
      critical roles in tumor progression and development. Its tumor-suppressor
      activity has been shown to depend on the propeptide region. Previous studies have
      reported that the expression levels of lysyl oxidase propeptide (LOX-PP) are
      associated with cancer of the breast, pancreas, lung, prostate and
      gastrointestinal system. However, to date, the exact effects and molecular
      mechanisms of LOX-PP in hepatocellular carcinoma progression are still unclear.
      The present study aimed to investigate the expression and clinical significance
      of LOX-PP in human hepatocellular carcinoma. First, 42 cases of hepatocellular
      carcinoma and corresponding adjacent non-cancerous tissues (ANCTs) were
      collected, and the expression of LOX-PP in these samples was assessed by
      immunohistochemistry (IHC). The clinicopathological characteristics of all
      patients were recorded. Next, in in vitro studies, recombinant adenovirus LOX (ad
      LOX-PP) was used to infect hepatocellular carcinoma cell lines to determine the
      function of LOX-PP. To determine whether ad-LOX-PP affects hepatocellular
      carcinoma cell survival, cell viability was examined by CCK-8 assay, and cell
      cycle progression was assessed by flow cytometry. We also investigated the
      effects of LOX-PP on the expression of cell cycle regulators (cyclin D1 and
      cyclin E) by western blot analysis. The migration and invasion capacities of
      hepatocellular carcinoma cells were observed by wound-healing and tranwell
      invasion assays. To further investigate how LOX-PP affects migration levels of
      matrix metallopeptidase (MMP)-2 and MMP-9 were assessed by western blot analysis.
      Additionally, markers of the PI3K and MAPK signaling pathway were detected to
      further confirm the mechanisms of LOX-PP. As a result, reduced expression of LOX
      PP was found in hepatocellular carcinoma tissues, when compared with that in the
      ANCTs (15 vs. 83%, P<0.01), and its expression was associated with tumor stage
      and distant metastasis (each P<0.05). Proliferation in hepatocellular carcinoma
      cells was significantly decreased in the ad-LOX-PP group as indicated by CCK-8
      assay. LOX-PP significantly reduced the expression of Ki-67, while prominent
      increases in the rate of apoptosis and cell cycle arrest were observed.
      Similarly, cell migration was significantly inhibited in the ad-LOX-PP group as
      evidenced by transwell invasion and wound-healing assays. The expression levels
      of MMP-2 and MMP-9 were attenuated in the ad-LOX-PP group, suggesting that LOX-PP
      inhibits hepatocellular carcinoma cell migration via down-regulation of MMPs
      expression. When LOX-PP expression was potentiated by an adenovirus containing
      LOX-PP, the expression of p-ERK was significantly downregulated, indicating that
      LOX-PP inhibits hepatocellular carcinoma cell proliferation and induces its
      apoptosis probably through downregulation of the MAPK/ERK pathway.

PMID- 24573151
TI  - Prognostic performance of a series of model for end-stage liver disease and
      respective Delta scores in patients with hepatitis B acute-on-chronic liver
      failure.
AB  - The present study aimed to compare the short-term prognostic performance of a
      series of model for end-stage liver disease (MELD) and respective delta (?)
      scores scoring systems in a population with acute-on-chronic hepatitis B liver
      failure (ACHBLF), and to investigate the potential effects from antivirals. A
      total of 77 patients with ACHBLF of mean age 46 years, 82% male, with 58.4%
      receiving antivirals, were recruited for this study. The ? scores for MELDs were
      defined as the changes one week after admission. Thirty-eight (49%) patients (22
      treated with antivirals) died within three months. The mean MELD and ?MELD scores
      of the survival group were 19.5 +/- 4.4 and 0.2 +/- 3.7 respectively, and those
      of the mortality group were 23.5 +/- 5.5 and 7.9 +/- 6, respectively. The area
      under the receiver operating characteristic curve (AUC) for MELD, integrated MELD
      (iMELD), MELD with the addition of serum sodium (MELD-Na), updated MELD (upMELD),
      MELD excluding the international normalized ratio (INR; MELD-XI), United Kingdom
      MELD (UKMELD) and their ? scores were 0.72, 0.81, 0.77, 0.69, 0.65, 0.77 and
      0.86, 0.83, 0.83, 0.82, 0.79 and 0.79, respectively. iMELD and MELD-Na
      significantly improved the accuracy of MELD (P<0.05). A cut-off value of 41.5 for
      the iMELD score can prognose 71% of mortalities with a specificity of 85%. In
      each pair of models, the ? score was superior to its counterpart, particularly
      when applied to patients with MELD <= 30. Decreased accuracy was observed for all
      models in the subset of patients treated with antivirals, although their baseline
      characteristics were comparable to those of untreated patients, while iMELD, MELD
      Na and respective ? models remained superior with regard to the predictability.
      The iMELD and MELD-Na models predicted three-month mortality more accurately,
      while the ? models were superior to their counterparts when MELD <= 30; however,
      their performance was altered by antivirals, and thus requires optimization.

PMID- 24573152
TI  - Behavioural flexibility allows an invasive vertebrate to survive in a semi-arid
      environment.
AB  - Plasticity or evolution in behavioural responses are key attributes of successful
      animal invasions. In northern Australia, the invasive cane toad (Rhinella marina)
      recently invaded semi-arid regions. Here, cane toads endure repeated daily bouts
      of severe desiccation and thermal stress during the long dry season (April
      October). We investigated whether cane toads have shifted their ancestral
      nocturnal rehydration behaviour to one that exploits water resources during the
      day. Such a shift in hydration behaviour could increase the fitness of individual
      toads by reducing exposure to desiccation and thermal stress suffered during the
      day even within terrestrial shelters. We used a novel method (acoustic tags) to
      monitor the daily hydration behaviour of 20 toads at two artificial reservoirs on
      Camfield station, Northern Territory. Remarkably, cane toads visited reservoirs
      to rehydrate during daylight hours, with peaks in activity between 9.00 and
      17.00. This diurnal pattern of rehydration activity contrasts with nocturnal
      rehydration behaviour exhibited by adult toads in their native geographical range
      and more mesic parts of Australia. Our results demonstrate that cane toads phase
      shift a key behaviour to survive in a harsh semi-arid landscape. Behavioural
      phase shifts have rarely been reported in invasive species but could facilitate
      ongoing invasion success. 

PMID- 24573153
TI  - Team of rivals: alliance formation in territorial songbirds is predicted by vocal
      signal structure.
AB  - Cooperation and conflict are regarded as diametric extremes of animal social
      behaviour, yet the two may intersect under rare circumstances. We here report
      that territorial competitors in a common North American songbird species, the
      chipping sparrow (Spizella passerina), sometimes form temporary coalitions in the
      presence of simulated territorial intruders. Moreover, analysis of birds' vocal
      mating signals (songs) reveals that coalitions occur nearly exclusively under
      specific triadic relationships, in which vocal performances of allies and
      simulated intruders exceed those of residents. Our results provide the first
      evidence that animals like chipping sparrows rely on precise assessments of
      mating signal features, as well as relative comparisons of signal properties
      among multiple animals in communication networks, when deciding when and with
      whom to form temporary alliances against a backdrop of competition and rivalry. 

PMID- 24573154
TI  - Programmed death in a unicellular organism has species-specific fitness effects.
AB  - Programmed cell death (PCD) is an ancient phenomenon and its origin and
      maintenance in unicellular life is unclear. We report that programmed death
      provides differential fitness effects that are species specific in the model
      organism Chlamydomonas reinhardtii. Remarkably, PCD in this organism not only
      benefits others of the same species, but also has an inhibitory effect on the
      growth of other species. These data reveal that the fitness effects of PCD can
      depend upon genetic relatedness. 

PMID- 24573155
TI  - Female cowbirds have more accurate spatial memory than males.
AB  - Brown-headed cowbirds (Molothrus ater) are obligate brood parasites. Only females
      search for host nests and they find host nests one or more days before placing
      eggs in them. Past work has shown that females have a larger hippocampus than
      males, but sex differences in spatial cognition have not been extensively
      investigated. We tested cowbirds for sex and seasonal differences in spatial
      memory on a foraging task with an ecologically relevant retention interval. Birds
      were trained to find one rewarded location among 25 after 24 h. Females made
      significantly fewer errors than males and took more direct paths to the rewarded
      location than males. Females and males showed similar search times, indicating
      there was no sex difference in motivation. This sex difference in spatial
      cognition is the reverse of that observed in some polygynous mammals and is
      consistent with the hypothesis that spatial cognition is adaptively specialized
      in this brood-parasitic species. 

PMID- 24573156
TI  - Sexually antagonistic association between paternal phenotype and offspring
      viability reinforces total selection on a sexually selected trait.
AB  - The evolution of conspicuous sexually selected traits, such as horns or antlers,
      has fascinated biologists for more than a century. Elaborate traits can only
      evolve if they substantially increase reproduction, because they probably incur
      survival costs to the bearer. Total selection on these traits, however, includes
      sexual selection on sires and viability selection on offspring and can be
      influenced by changes in each of these components. Non-random associations
      between paternal phenotype and offspring viability may thus affect total
      selection on sexually selected traits. Long-term data on wild bighorn sheep (Ovis
      canadensis) provide the first evidence in nature that association between
      paternal phenotype and lamb viability strengthens total selection on horn size of
      adult rams, a sexually selected trait. The association of paternal horn length
      and offspring viability was sexually antagonistic: long-horned males sired sons
      with high viability but daughters of low viability. These results shed new light
      on the evolutionary dynamics of an iconic sexually selected trait and have
      important implications for sustainable wildlife management. 

PMID- 24573158
TI  - Pedobacter jejuensis sp. nov., isolated from soil of a pine grove, and emended
      description of the genus Pedobacter.
AB  - A Gram-stain-negative, strictly aerobic, non-motile, rod-shaped bacterial strain,
      THG-DR3T, was isolated from soil of a pine grove in Jeju island, Republic of
      Korea. Strain THG-DR3T grew optimally at 20-25  degrees C, at pH 7.0-8.0 and in
      R2A broth without added NaCl. 16S rRNA gene sequence analysis indicated that
      strain THG-DR3T belongs to the genus Pedobacter. The closest relatives based on
      16S rRNA gene sequence similarity were Pedobacter aquatilis AR107T (98.0%),
      Pedobacter alluvionis NWER-II11T (97.7%), Pedobacter borealis G-1T (97.7%) and
      Pedobacter ginsengiterrae DCY49T (97.4%). The G+C content of the genomic DNA of
      strain THG-DR3T was 47.5 mol%. Levels of DNA-DNA relatedness between strain THG
      DR3T and its closest phylogenetic neighbours were below 44.7%. The presence of
      menaquinone 7 and of iso-C15:0 and summed feature 3 (comprising C16:1omega7c
      and/or C16:1omega6c) as the major fatty acids supported the affiliation of strain
      THG-DR3T to the genus Pedobacter. The polar lipids of strain THG-DR3T consisted
      of phosphatidylethanolamine, three unidentified aminophospholipids, five
      unidentified aminolipids and three unidentified lipids. The results of
      physiological and biochemical tests allowed the differentiation of strain THG
      DR3T from recognized species of the genus Pedobacter. Strain THG-DR3T (=KACC
      17172T=JCM 18824T) is proposed as the type strain of a novel species of the genus
      Pedobacter, Pedobacter jejuensis sp. nov. An emended description of the genus
      Pedobacter is also proposed.

PMID- 24573159
TI  - Comparative polyphasic characterization of Streptococcus phocae strains with
      different host origin and description of the subspecies Streptococcus phocae
      subsp. salmonis subsp. nov.
AB  - A polyphasic study was undertaken to clarify the taxonomic position of
      Streptococcus phocae strains isolated from Atlantic salmon (Salmo salar) cage
      farmed in Chile. Four salmon and three seal isolates showed minor differences in
      the SDS-PAGE protein analysis. Thus, a major protein band present in the salmon
      isolates, of approximately 22.4 kDa, was absent in the pinniped strains,
      regardless of the growth media employed. In addition, the pinniped strains showed
      protein bands with molecular masses of 71.5 and 14.2 kDa, when grown on
      trypticase soy agar supplemented with 1% NaCl, or 25.6 kDa, when grown on
      Columbia blood agar, not present in the Atlantic salmon strains. A high
      similarity in the matrix-assisted laser desorption/ionization time-of-flight
      (MALDI-TOF) MS spectra of the strains was observed, although some minor peaks
      were absent in the fish isolates. Fatty acid methyl esters from isolates with
      different host origin significantly (P<0.05) differed in the content of C16:0,
      C17:0, C18:1omega9c, C20:4omega6,9,12,15c and summed features 3, 5 and 8. The
      salmon isolates formed a separate cluster in the phylogenetic analysis of
      housekeeping genes, separately or as concatenated sequences. Sequence divergences
      among salmon and seal strains were in the range of inter-subspecies
      differentiation for groEL (2.5%), gyrB (1.8%), recN (2.1%), rpoB (1.7%) and sodA
      (2.0%) genes. DNA-DNA hybridization results confirmed those of sequencing,
      showing reassociation values between seal and salmon strains close to the
      borderline of species definition. Differences in growth at low temperatures and
      in the haemolytic capacities were also observed between both groups of isolates.
      On the basis of all these results, the salmon isolates represent a novel
      subspecies of S. phocae, for which the name Streptococcus phocae subsp. salmonis
      subsp. nov. is proposed. The type strain is C-4T (=CECT 7921T=DSM 24768T). The
      subspecies Streptococcus phocae subsp. phocae subsp. nov. is automatically
      created. An emended description of S. phocae is also provided.

PMID- 24573160
TI  - Pseudopedobacter beijingensis gen. nov., sp. nov., isolated from coking
      wastewater activated sludge, and reclassification of Pedobacter saltans as
      Pseudopedobacter saltans comb. nov.
AB  - A taxonomic study was carried out on strain GCS-AE-31(T), which was isolated from
      a phenol-degrading consortium, enriched from coking wastewater activated sludge
      of the Beijing Shougang Company Limited during the screening of phenol-degrading
      bacteria. Cells of strain GCS-AE-31(T) were Gram-stain-negative, short rods,
      motile by gliding, oxidase- and catalase-positive. Growth was observed at
      salinities of 0-3% and at temperatures of 10-37  degrees C. On the basis of 16S
      rRNA gene sequence similarity, strain GCS-AE-31(T) was most closely related to
      Pedobacter saltans LMG 10337(T) (96.17%), but it showed low similarity to all
      other species of the genus Pedobacter (89.28-92.45%). It also showed low 16S rRNA
      gene similarity to all other species of the family Sphingobacteriaceae (87.25
      92.45%) examined. The dominant fatty acids were iso-C(15 : 0), summed feature 3
      (C(16 : 1)omega7c/C(16 : 1)omega6c), anteiso-C(15 : 0) and iso-C(17 : 0) 3-OH.
      The menaquinones were MK-7 (95.5%) and MK-6 (4.5%). The polar lipids were
      phosphatidylethanolamine, three aminolipids and three unknown phospholipids.
      Sphingolipid was present. The G+C content of the chromosomal DNA was 36.2 mol%.
      According to its phylogenetic position and phenotypic traits, the novel strain
      could not be assigned to the genus Pedobacter; it should be classified as
      representing a novel species of a novel genus in the family Sphingobacteriaceae,
      for which the name Pseudopedobacter beijingensis gen. nov., sp. nov. is proposed
      (type strain GCS-AE-31(T) = MCCC 1A01299(T) = CGMCC 1.12329(T) = LMG 27180(T)).
      The misclassified species Pedobacter saltans is transferred to the novel genus as
      Pseudopedobacter saltans comb. nov. (type strain LMG 10337(T) = MCCC 1A06472(T) =
      DSM 12145(T) = CCUG 39354(T) = CIP 105500(T) = JCM 21818(T) = NBRC 100064(T)).

PMID- 24573161
TI  - Nitrolancea hollandica gen. nov., sp. nov., a chemolithoautotrophic nitrite
      oxidizing bacterium isolated from a bioreactor belonging to the phylum
      Chloroflexi.
AB  - A novel nitrite-oxidizing bacterium (NOB), strain Lb(T), was isolated from a
      nitrifying bioreactor with a high loading of ammonium bicarbonate in a mineral
      medium with nitrite as the energy source. The cells were oval (lancet-shaped)
      rods with pointed edges, non-motile, Gram-positive (by staining and from the cell
      wall structure) and non-spore-forming. Strain Lb(T) was an obligately aerobic,
      chemolitoautotrophic NOB, utilizing nitrite or formate as the energy source and
      CO2 as the carbon source. Ammonium served as the only source of assimilated
      nitrogen. Growth with nitrite was optimal at pH 6.8-7.5 and at 40  degrees C
      (maximum 46  degrees C). The membrane lipids consisted of C20 alkyl 1,2-diols
      with the dominant fatty acids being 10MeC18 and C(18 : 1)omega9. The
      peptidoglycan lacked meso-DAP but contained ornithine and lysine. The dominant
      lipoquinone was MK-8. Phylogenetic analyses of the 16s rRNA gene sequence placed
      strain Lb(T) into the class Thermomicrobia of the phylum Chloroflexi with
      Sphaerobacter thermophilus as the closest relative. On the basis of physiological
      and phylogenetic data, it is proposed that strain Lb(T) represents a novel
      species of a new genus, with the suggested name Nitrolancea hollandica gen. nov.,
      sp. nov. The type strain of the type species is Lb(T) ( = DSM 23161(T) = UNIQEM
      U798(T)).

PMID- 24573162
TI  - Metschnikowia laotica f.a., sp. nov., a dimorphic, pigment-producing yeast
      species isolated from fruit.
AB  - Eight strains with identical sequences of the D1/D2 domains of the large subunit
      rRNA genes were isolated from fallen fruits in two distant localities in Laos.
      These strains represent a novel dimorphic budding yeast species producing
      invasive pseudohyphae and a brown pigment when growing on media containing quinic
      acid as the sole carbon source or tryptophan as the sole nitrogen source.
      Phylogenetic analysis of the sequences of the D1/D2 domains, the internal
      transcribed spacer (ITS) regions and the 18S rRNA genes placed the novel species
      in the Metschnikowia clade close to Candida torresii, Metschnikowia drosophilae
      and Candida danieliae. The taxonomic name Metschnikowia laotica f.a., sp. nov.,
      reflecting the geographical origin of the isolates, is proposed for the novel
      species. The type strain is 11-524(T) ( = CBS 12961(T) = NCAIM Y.02124(T) = CCY
      64-4-1(T)). The Mycobank number is MB 807383.

PMID- 24573163
TI  - Aridibacter famidurans gen. nov., sp. nov. and Aridibacter kavangonensis sp.
      nov., two novel members of subdivision 4 of the Acidobacteria isolated from
      semiarid savannah soil.
AB  - Acidobacteria constitute an abundant fraction of the soil microbial community and
      are currently divided into 26 subdivisions. Most cultivated members of the
      Acidobacteria are affiliated with subdivision 1, while only a few representatives
      of subdivisions 3, 4, 8, 10 and 23 have been isolated and described so far. Two
      novel isolates of subdivision 4 of the Acidobacteria were isolated from
      subtropical savannah soils and are characterized in the present work. Cells of
      strains A22_HD_4H(T) and Ac_23_E3(T) were immotile rods that divided by binary
      fission. Colonies were pink and white, respectively. The novel strains
      A22_HD_4H(T) and Ac_23_E3(T) were aerobic mesophiles with a broad range of
      tolerance towards pH (4.0-9.5 and 3.5-10.0, respectively) and temperature (15-44
      and 12-47  degrees C, respectively). Both showed chemo-organoheterotrophic growth
      on some sugars, the amino sugar N-acetylgalactosamine, a few amino acids, organic
      acids and various complex protein substrates. Major fatty acids of A22_HD_4H(T)
      and Ac_23_E3(T) were iso-C(15 : 0), summed feature 1 (C(13 : 0) 3-OH/iso-C(15 :
      1) H), summed feature 3 (C(16 : 1)omega7c/C(16 : 1)omega6c) and anteiso-C(17 :
      0). The major quinone was MK-8; in addition, MK-7 occurred in small amounts. The
      DNA G+C contents of A22_HD_4H(T) and Ac_23_E3(T) were 53.2 and 52.6 mol%,
      respectively. The closest described relative was Blastocatella fastidiosa A2
      16(T), with 16S rRNA gene sequence identity of 93.2 and 93.3%, respectively.
      Strains A22_HD_4H(T) and Ac_23_E3(T) displayed 16S rRNA gene sequence similarity
      of 97.4% to each other. On the basis of the low DNA-DNA hybridization value, the
      two isolates represent different species. Based on morphological, physiological
      and molecular characteristics, the new genus Aridibacter gen. nov. is proposed,
      with two novel species, the type species Aridibacter famidurans sp. nov. (type
      strain A22_HD_4H(T) = DSM 26555(T) = LMG 27985(T)) and a second species,
      Aridibacter kavangonensis sp. nov. (type strain Ac_23_E3(T) = DSM 26558(T) = LMG
      27597(T)).

PMID- 24573164
TI  - Brugada syndrome disease phenotype explained in apparently benign sodium channel
      mutations.
AB  - BACKGROUND: Brugada syndrome (BrS) is an arrhythmogenic disorder that has been
      linked to mutations in SCN5A, the gene encoding for the pore-forming alpha
      subunit of the cardiac sodium channel. Typically, BrS mutations in SCN5A result
      in a reduction of sodium current with some mutations even exhibiting a dominant
      negative effect on wild-type (WT) channels, thus leading to an even more
      prominent decrease in current amplitudes. However, there is also a category of
      apparently benign (atypical) BrS SCN5A mutations that in vitro demonstrates only
      minor biophysical defects. It is therefore not clear how these mutations produce
      a BrS phenotype. We hypothesized that similar to dominant-negative mutations,
      atypical mutations could lead to a reduction in sodium currents when coexpressed
      with WT to mimic the heterozygous patient genotype. METHODS AND RESULTS: WT and
      atypical BrS mutations were coexpressed in Human Embryonic Kidney-293 cells,
      showing a reduction in sodium current densities similar to typical BrS mutations.
      Importantly, this reduction in sodium current was also seen when the atypical
      mutations were expressed in rat or human cardiomyocytes. This decrease in current
      density was the result of reduced surface expression of both mutant and WT
      channels. CONCLUSIONS: Taken together, we have shown how apparently benign SCN5A
      BrS mutations can lead to the ECG abnormalities seen in patients with BrS through
      an induced defect that is only present when the mutations are coexpressed with WT
      channels. Our work has implications for risk management and stratification for
      some SCN5A-implicated BrS patients.

PMID- 24573165
TI  - Proteome-based systems biology analysis of the diabetic mouse aorta reveals major
      changes in fatty acid biosynthesis as potential hallmark in diabetes mellitus
      associated vascular disease.
AB  - BACKGROUND: Macrovascular complications of diabetes mellitus are a major risk
      factor for cardiovascular morbidity and mortality. Currently, studies only
      partially described the molecular pathophysiology of diabetes mellitus-associated
      effects on vasculature. However, better understanding of systemic effects is
      essential in unraveling key molecular events in the vascular tissue responsible
      for disease onset and progression. METHODS AND RESULTS: Our overall aim was to
      get an all-encompassing view of diabetes mellitus-induced key molecular changes
      in the vasculature. An integrative proteomic and bioinformatics analysis of data
      from aortic vessels in the low-dose streptozotocin-induced diabetic mouse model
      (10 animals) was performed. We observed pronounced dysregulation of molecules
      involved in myogenesis, vascularization, hypertension, hypertrophy (associated
      with thickening of the aortic wall), and a substantial reduction of fatty acid
      storage. A novel finding is the pronounced downregulation of glycogen synthase
      kinase-3beta (Gsk3beta) and upregulation of molecules linked to the tricarboxylic
      acid cycle (eg, aspartate aminotransferase [Got2] and hydroxyacid-oxoacid
      transhydrogenase [Adhfe1]). In addition, pathways involving primary alcohols and
      amino acid breakdown are altered, potentially leading to ketone-body production.
      A number of these findings were validated immunohistochemically. Collectively,
      the data support the hypothesis that in this diabetic model, there is an
      overproduction of ketone-bodies within the vessels using an alternative
      tricarboxylic acid cycle-associated pathway, ultimately leading to the
      development of atherosclerosis. CONCLUSIONS: Streptozotocin-induced diabetes
      mellitus in animals leads to a reduction of fatty acid biosynthesis and an
      upregulation of an alternative ketone-body formation pathway. This working
      hypothesis could form the basis for the development of novel therapeutic
      intervention and disease management approaches.

PMID- 24573166
TI  - Restoration of mountain big sagebrush steppe following prescribed burning to
      control western juniper.
AB  - Western juniper (Juniperus occidentalis ssp. occidentalis Hook) encroachment into
      mountain big sagebrush (Artemisia tridentata spp. vaseyana (Rydb.) Beetle) steppe
      has reduced livestock forage production, increased erosion risk, and degraded
      sagebrush-associated wildlife habitat. Western juniper has been successfully
      controlled with partial cutting followed by prescribed burning the next fall, but
      the herbaceous understory and sagebrush may be slow to recover. We evaluated the
      effectiveness of seeding perennial herbaceous vegetation and sagebrush at five
      sites where juniper was controlled by partially cutting and prescribed burning.
      Treatments tested at each site included an unseeded control, herbaceous seed mix
      (aerially seeded), and the herbaceous seed mix plus sagebrush seed. In the third
      year post-treatment, perennial grass cover and density were twice as high in
      plots receiving the herbaceous seed mix compared to the control plots. Sagebrush
      cover and density in the sagebrush seeded plots were between 74- and 290-fold and
      62- and 155-fold greater than the other treatments. By the third year after
      treatment, sagebrush cover was as high as 12 % in the sagebrush seeded plots and
      between 0 % and 0.4 % where it was not seeded. These results indicate that aerial
      seeding perennial herbaceous vegetation can accelerate the recovery of perennial
      grasses which likely stabilize the site. Our results also suggest that seeding
      mountain big sagebrush after prescribed burning encroaching juniper can rapidly
      recover sagebrush cover and density. In areas where sagebrush habitat is limited,
      seeding sagebrush after juniper control may increase sagebrush habitat and
      decrease the risks to sagebrush-associated species. 

PMID- 24573167
TI  - Identification of potential essential fish habitats for skates based on fishers'
      knowledge.
AB  - Understanding of spatio-temporal patterns of sensitive fish species such as
      skates (Rajidae) is essential for implementation of conservation measures. With
      insufficient survey data available for these species in Portuguese Continental
      waters, this study shows that fishery-dependent data associated with fishers'
      knowledge can be used to identify potential Essential Fish Habitats (EFH) for
      seven skate species. Sites with similar geomorphology were associated with the
      occurrence of juveniles and/or adults of the same group of species. For example,
      sites deeper than 100 m with soft sediment include predominantly adults of Raja
      clavata, and are the habitat for egg deposition of this species. Raja undulata
      and R. microocellata are the more coastal species, preferring sand or gravel
      habitats, while coastal areas with rocks and sand seabed are potential nursery
      areas for R. brachyura, R. montagui and R. clavata. The main output of this study
      is the identification of preferential fishing sites enclosing potential EFH for
      some species, associated with egg-laying and nursery grounds. The location of
      these areas will be considered for future seasonal closures, and studies will be
      conducted to evaluate the biological and socio-economic impacts of such measures.
      As in the past, fishermen will collaborate in the process of evaluating those
      impacts, since they have practical and applied knowledge that is extremely
      valuable for evaluating the advantages and disadvantages of such closures. In
      conclusion, this study is a first contribution to the understanding and
      identification of EFH for skate species, associated with nursery and egg
      deposition sites, with direct application to management. 

PMID- 24573168
TI  - Perspective of humanized mouse models for assessing PK/PD and toxic profile of
      drug candidates in preclinical study.

PMID- 24573169
TI  - The cutting-edge of clinical therapeutics based on
      pharmacokinetic/pharmacodynamic theory. Preface.

PMID- 24573170
TI  - Censoring weighted separate-and-conquer rule induction from survival data.
AB  - OBJECTIVES: Rule induction is one of the major methods of machine learning. Rule
      based models can be easily read and interpreted by humans, that makes them
      particularly useful in survival studies as they can help clinicians to better
      understand analysed data and make informed decisions about patient treatment.
      Although of such usefulness, there is still a little research on rule learning in
      survival analysis. In this paper we take a step towards rule-based analysis of
      survival data. METHODS: We investigate so-called covering or separate-and-conquer
      method of rule induction in combination with a weighting scheme for handling
      censored observations. We also focus on rule quality measures being one of the
      key elements differentiating particular implementations of separate-and-conquer
      rule induction algorithms. We examine 15 rule quality measures guiding rule
      induction process and reflecting a wide range of different rule learning
      heuristics. RESULTS: The algorithm is extensively tested on a collection of 20
      real survival datasets and compared with the state-of-the-art survival trees and
      random survival forests algorithms. Most of the rule quality measures outperform
      Kaplan-Meier estimate and perform at least equally well as tree-based algorithms.
      CONCLUSIONS: Separate-and-conquer rule induction in combination with weighting
      scheme is an effective technique for building rule-based models of survival data
      which, according to predictive accuracy, are competitive with tree-based
      representations.

PMID- 24573171
TI  - Effects of topical sphingosine-1-phosphate 1 receptor agonist on corneal
      allograft in mice.
AB  - PURPOSE: The aim of this study was to compare the antirejection effects of
      topical selective sphingosine-1-phosphate 1 receptor (S1P1) agonist and
      cyclosporine A (CsA) on the acceptance of a transplanted, allogeneic cornea graft
      in a murine animal model. METHODS: Fifty-six BALB/c mice were randomly divided
      into 4 groups. All the mice received corneal grafts from 28 C57BL/6 donors.
      Experimental recipients were treated with 0.25%, 0.5% S1P1 agonist suspension eye
      drops or 1% CsA eye drops 4 times a day after the corneal graft was performed.
      Controls received no treatment. The corneal grafts were imaged and evaluated with
      clinical scoring. The excised corneal sections 14 days after transplantation were
      stained using hematoxylin-eosin for histopathological evaluation. CD86+ and MHC
      II+ dendritic cells in corneal samples were identified by immunohistochemical
      staining. The expression of mRNA in the cornea was evaluated using real-time
      quantitative PCR for interleukin-2, interferon-gamma, and cytotoxic T-lymphocyte
      antigen 4. RESULTS: Corneal graft survival was prolonged by treatment with 0.5%
      S1P1 agonist and 1% CsA (P < 0.01, respectively) when compared with that in the
      control in clinical scoring. In addition, topical application of 0.5% S1P1
      increased the cytotoxic T-lymphocyte antigen 4 mRNA expression of the corneal
      grafts. There were significant differences observed with 0.5% S1P1 and agonist 1%
      CsA (P < 0.01, respectively) when compared with the values of the control group
      in histology scoring. CONCLUSIONS: Topical 0.5% S1P1 agonist is as effective as
      1% CsA, and both can effectively prolong the survival of corneal allografts in
      mice.

PMID- 24573172
TI  - Reactivity and catalytic activity of tert-butoxy-aluminium hydride reagents.
AB  - The reactivity and catalytic activities of the tert-butoxy aluminium hydride
      reagents [((t)BuO)xAlH3-x] [x = 1 (1), 2 (2)] and (L)Li[((t)BuO)2AlH2] [L = THF
      (3), 1,4-dioxane (4)] are investigated. The structural characterisation of the
      novel compounds 3 and 4 shows that the nature of the hydridic species present is
      affected dramatically by the donor ligand coordinating the Li(+) cation.
      Stoichiometric reaction of 1 with pyridine gives [(1,4-H-pyrid-1-yl)4Al](
      )[(pyridine)4AlH2](+) (5) while reaction with the amine-borane Me2NHBH3 in the
      presence of PMDETA [(Me2NCH2CH2)2NMe] affords [(PMDETA)AlH2](+)[(BH3)2NMe2](-)
      (6). The reagents 1-4 catalyse the dehydrocoupling reaction of the amine-borane
      Me2NHBH3 into the ring compound [Me2NBH2]2, with the activity decreasing in the
      order 1?2~3 > 4. The greater reactivity of the neutral dihydride 1 provides the
      potential basis for future catalytic optimisation. 

PMID- 24573173
TI  - Melanocytes as instigators and victims of oxidative stress.
AB  - Epidermal melanocytes are particularly vulnerable to oxidative stress owing to
      the pro-oxidant state generated during melanin synthesis, and to the intrinsic
      antioxidant defenses that are compromised in pathologic conditions. Melanoma is
      thought to be oxidative stress driven, and melanocyte death in vitiligo is
      thought to be instigated by a highly pro-oxidant state in the epidermis. We
      review the current knowledge about melanin and the redox state of melanocytes,
      how paracrine factors help counteract oxidative stress, the role of oxidative
      stress in melanoma initiation and progression and in melanocyte death in
      vitiligo, and how this knowledge can be harnessed for melanoma and vitiligo
      treatment. 

PMID- 24573175
TI  - T-type channels in the sino-atrial and atrioventricular pacemaker mechanism.
AB  - Cardiac automaticity is a fundamental physiological function in vertebrates.
      Heart rate is under the control of several neurotransmitters and hormones and is
      permanently adjusted by the autonomic nervous system to match the physiological
      demand of the organism. Several classes of ion channels and proteins involved in
      intracellular Ca(2+) handling contribute to pacemaker activity. Voltage-dependent
      T-type Ca(2+) channels are an integral part of the complex mechanism underlying
      pacemaking. T-type channels also contribute to impulse conduction in mice and
      humans. Strikingly, T-type channel isoforms are co-expressed in the cardiac
      conduction system with other ion channels that play a major role in pacemaking
      such as f- (HCN4) and L-type Cav1.3 channels. Pharmacologic inhibition of T-type
      channels reduces the spontaneous activity of isolated pacemaker myocytes of the
      sino-atrial node, the dominant heart rhythmogenic centre. Target inactivation of
      T-type Cav3.1 channels abolishes I Ca,T in both sino-atrial and atrioventricular
      myocytes and reduces the daily heart rate of freely moving mice. Cav3.1 channels
      contribute also to automaticity of the atrioventricular node and to ventricular
      escape rhythms, thereby stressing the importance of these channels in
      automaticity of the whole cardiac conduction system. Accordingly, loss-of
      function of Cav3.1 channels contributes to severe form of congenital bradycardia
      and atrioventricular block in paediatric patients. 

PMID- 24573174
TI  - Exercise training in adverse cardiac remodeling.
AB  - Cardiac remodeling in response to a myocardial infarction or chronic pressure
      overload is an independent risk factor for the development of heart failure. In
      contrast, cardiac remodeling produced by regular physical exercise is associated
      with a decreased risk for heart failure. There is evidence that exercise training
      has a beneficial effect on disease progression and survival in patients with
      cardiac remodeling and dysfunction, but concern has also been expressed that
      exercise training may aggravate pathological remodeling and dysfunction. Here we
      present studies from our laboratory into the effects of exercise training on
      pathological cardiac remodeling and dysfunction in mice. The results indicate
      that even in the presence of a large infarct, exercise training exerts beneficial
      effects on the heart. These effects were mimicked in part by endothelial nitric
      oxide synthase (eNOS) overexpression and abrogated by eNOS deficiency,
      demonstrating the importance of nitric oxide signaling in mediating the cardiac
      effects of exercise. Exercise prior to a myocardial infarction was also
      cardioprotective. In contrast, exercise tended to aggravate pathological cardiac
      remodeling and dysfunction in the setting of pressure-overload produced by an
      aortic stenosis. These observations emphasize the critical importance of the
      underlying pathological stimulus for cardiac hypertrophy and remodeling, in
      determining the effects of exercise training. Future studies are needed to define
      the influence of exercise type, intensity and duration in different models and
      severities of pathological cardiac remodeling. Together such studies will aid in
      optimizing the therapy of exercise training in the setting of cardiovascular
      disease. 

PMID- 24573176
TI  - A human rights approach to an international code of conduct for genomic and
      clinical data sharing.
AB  - Fostering data sharing is a scientific and ethical imperative. Health gains can
      be achieved more comprehensively and quickly by combining large, information-rich
      datasets from across conventionally siloed disciplines and geographic areas.
      While collaboration for data sharing is increasingly embraced by policymakers and
      the international biomedical community, we lack a common ethical and legal
      framework to connect regulators, funders, consortia, and research projects so as
      to facilitate genomic and clinical data linkage, global science collaboration,
      and responsible research conduct. Governance tools can be used to responsibly
      steer the sharing of data for proper stewardship of research discovery, genomics
      research resources, and their clinical applications. In this article, we propose
      that an international code of conduct be designed to enable global genomic and
      clinical data sharing for biomedical research. To give this proposed code
      universal application and accountability, however, we propose to position it
      within a human rights framework. This proposition is not without precedent:
      international treaties have long recognized that everyone has a right to the
      benefits of scientific progress and its applications, and a right to the
      protection of the moral and material interests resulting from scientific
      productions. It is time to apply these twin rights to internationally
      collaborative genomic and clinical data sharing. 

PMID- 24573177
TI  - Enhanced noise at high bias in atomic-scale Au break junctions.
AB  - Heating in nanoscale systems driven out of equilibrium is of fundamental
      importance, has ramifications for technological applications, and is a challenge
      to characterize experimentally. Prior experiments using nanoscale junctions have
      largely focused on heating of ionic degrees of freedom, while heating of the
      electrons has been mostly neglected. We report measurements in atomic-scale Au
      break junctions, in which the bias-driven component of the current noise is used
      as a probe of the electronic distribution. At low biases (<150 mV) the noise is
      consistent with expectations of shot noise at a fixed electronic temperature. At
      higher biases, a nonlinear dependence of the noise power is observed. We consider
      candidate mechanisms for this increase, including flicker noise (due to ionic
      motion), heating of the bulk electrodes, nonequilibrium electron-phonon effects,
      and local heating of the electronic distribution impinging on the ballistic
      junction. We find that flicker noise and bulk heating are quantitatively unlikely
      to explain the observations. We discuss the implications of these observations
      for other nanoscale systems, and experimental tests to distinguish vibrational
      and electron interaction mechanisms for the enhanced noise. 

PMID- 24573179
TI  - CDKN3 is an independent prognostic factor and promotes ovarian carcinoma cell
      proliferation in ovarian cancer.
AB  - Cyclin-dependent kinase inhibitor 3 (CDKN3) has been reported to promote tumor
      genesis. Since it is unclear whether CDKN3 participates in the development of
      epithelial ovarian cancer (EOC), this study assessed the association between
      CDKN3 expression and cell biological functions, and demonstrated the clinical
      significance and prognosis of CDKN3 in EOC. CDKN3 expression was evaluated in 97
      cases of tumor tissue by immunohistochemistry and in 60 tissues by western
      blotting. The clinical correlation was analyzed by Kaplan-Meier method and Cox
      hazards model. The molecular functional roles of CDKN3 in ovarian cancer cell
      line OVCAR3 were examined by small interfering RNA-mediated depletion of the
      protein followed by analyses of cell proliferation and invasion. Twenty-three out
      of 30 (76.7%) human EOC tissues exhibited stronger levels of CDKN3 protein
      compared with 10 out of 30 (33.3%) human ovarian surface epithelial (HOSE)
      tissues. The mean level of CDKN3 expression in the EOC tissues was 3.35-fold that
      in the HOSE tissues. CDKN3 protein was found to be overexpressed in 68.0% of the
      EOC samples and was correlated with poor patient survival (P<0.05). Furthermore,
      expression of CDKN3 was significantly associated with FIGO stage, recurrence and
      residual tumor size (P<0.05), and the CDKN3 status was a significant prognostic
      factor for EOC patients (P=0.005). In addition, depletion of CDKN3 expression
      inhibited the growth and clonogenic potential of the OVCAR3 cell line. Our
      present research found that CDKN3 may play an important role in the development
      and proliferation of EOC. CDKN3 may be used as a novel tumor marker to predict
      the prognosis of EOC. 

PMID- 24573180
TI  - Activation of the carotid chemoreflex secondary to muscle metaboreflex
      stimulation in men.
AB  - Recent work has shown that the carotid chemoreceptor (CC) contributes to
      sympathetic control of cardiovascular function during exercise, despite no
      evidence of increased circulating CC stimuli, suggesting enhanced CC
      activity/sensitivity. As interactions between metaboreceptors and chemoreceptors
      have been previously observed, the purpose of this study was to isolate the
      metaboreflex while acutely stimulating or inhibiting the CC to determine whether
      the metaboreflex increased CC activity/sensitivity. Fourteen young healthy men
      (height: 177.0 +/- 2.1 cm, weight: 85.8 +/- 5.5 kg, age: 24.6 +/- 1.1 yr)
      performed three trials of 40% maximal voluntary contraction handgrip for 2 min,
      followed by 3 min of postexercise circulatory occlusion (PECO) to stimulate the
      metaboreflex. In random order, subjects either breathed room air, hypoxia (target
      SPo2 = 85%), or hyperoxia (FiO2 = 1.0) during the PECO to modulate the
      chemoreflex. After these trials, a resting hypoxia trial was conducted without
      handgrip or PECO. Ventilation (Ve), heart rate (HR), blood pressure, and muscle
      sympathetic nervous activity (MSNA) data were continuously obtained. Relative to
      normoxic PECO, inhibition of the CC during hyperoxic PECO resulted in lower MSNA
      (P = 0.038) and HR (P = 0.021). Relative to normoxic PECO, stimulation of the CC
      during hypoxic PECO resulted in higher HR (P < 0.001) and Ve (P < 0.001). The
      ventilatory and MSNA responses to hypoxic PECO were not greater than the sum of
      the responses to hypoxia and PECO individually, indicating that the CC are not
      sensitized during metaboreflex activation. These results demonstrate that
      stimulation of the metaboreflex activates, but does not sensitize the CC, and
      help explain the enhanced CC activity with exercise. 

PMID- 24573178
TI  - Biodistribution of mesenchymal stem cell-derived extracellular vesicles in a
      model of acute kidney injury monitored by optical imaging.
AB  - Mesenchymal stem cells (MSCs) contribute to the recovery of tissue injury,
      providing a paracrine support. Cell-derived extracellular vesicles (EVs),
      carrying membrane and cytoplasmatic constituents of the cell of origin, have been
      described as a fundamental mechanism of intercellular communication. We
      previously demonstrated that EVs derived from human MSCs accelerated recovery
      following acute kidney injury (AKI) in vivo. The aim of the present study was to
      investigate the biodistribution and the renal localization of EVs in AKI. For
      this purpose, two methods for EV labeling suitable for in vivo tracking with
      optical imaging (OI), were employed using near infrared (NIR) dye (DiD): i)
      labeled EVs were generated by MSCs pre-incubated with NIR dye and collected from
      cell supernatants; ii) purified EVs were directly labeled with NIR dye. EVs
      obtained with these two procedures were injected intravenously (i.v.) into mice
      with glycerol-induced AKI and into healthy mice to compare the efficacy of the
      two labeling methods for in vivo detection of EVs at the site of damage. We found
      that the labeled EVs accumulated specifically in the kidneys of the mice with AKI
      compared with the healthy controls. After 5 h, the EVs were detectable in whole
      body images and in dissected kidneys by OI with both types of labeling
      procedures. The directly labeled EVs showed a higher and brighter fluorescence
      compared with the labeled EVs produced by cells. The signal generated by the
      directly labeled EVs was maintained in time, but provided a higher background
      than that of the labeled EVs produced by cells. The comparison of the two methods
      indicated that the latter displayed a greater specificity for the injured kidney.

PMID- 24573181
TI  - Hindbrain energy status controls hypothalamic metabolic and neuropeptide signals.
      Focus on "Hindbrain lactostasis regulates hypothalamic AMPK activity and
      hypothalamic metabolic neurotransmitter mRNA and protein responses to
      hypoglycemia".

PMID- 24573182
TI  - Development of attenuated baroreflexes in obese Zucker rats coincides with
      impaired activation of nucleus tractus solitarius.
AB  - Adult obese Zucker rats (OZR; >12 wk) develop elevated sympathetic nerve activity
      (SNA) and mean arterial pressure (MAP) with impaired baroreflexes compared with
      adult lean Zucker rats (LZR) and juvenile OZR (6-7 wk). In adult OZR,
      baroreceptor afferent nerves respond normally to changes in MAP, whereas
      electrical stimulation of baroreceptor afferent fibers produces smaller
      reductions in SNA and MAP compared with LZR. We hypothesized that impaired
      baroreflexes in OZR are linked to reduced activation of brain stem sites that
      mediate baroreflexes. In conscious adult rats, a hydralazine (HDZ)-induced
      reduction in MAP evoked tachycardia that was initially blunted in OZR, but
      equivalent to LZR within 5 min. In agreement, HDZ-induced expression of c-Fos in
      the rostral ventrolateral medulla (RVLM) was comparable between groups. In
      contrast, phenylephrine (PE)-induced rise in MAP evoked markedly attenuated
      bradycardia with dramatically reduced c-Fos expression in the nucleus tractus
      solitarius (NTS) of adult OZR compared with LZR. However, in juvenile rats, PE
      induced hypertension evoked comparable bradycardia in OZR and LZR with similar or
      augmented c-Fos expression in NTS of the OZR. In urethane-anesthetized rats,
      microinjections of glutamate into NTS evoked equivalent decreases in SNA, heart
      rate (HR), and MAP in juvenile OZR and LZR, but attenuated decreases in SNA and
      MAP in adult OZR. In contrast, microinjections of glutamate into the caudal
      ventrolateral medulla, a target of barosensitive NTS neurons, evoked comparable
      decreases in SNA, HR, and MAP in adult OZR and LZR. These data suggest that OZR
      develop impaired glutamatergic activation of the NTS, which likely contributes to
      attenuated baroreflexes in adult OZR. 

PMID- 24573186
TI  - A comparison between the diffusion-reaction and slow axonal transport models for
      predicting tau distribution along an axon.
AB  - This paper developed equations describing steady-state tau distributions for
      three versions of the diffusion-reaction model of tau transport: a model with
      constant kinetic rates, a model that additionally accounts for tau diffusion
      along microtubules (MTs) and a model with a modulated rate of tau attachment to
      MTs. We demonstrated that, for the model with constant kinetic rates, the
      concentration of free tau in the cytoplasm was determined by a single
      dimensionless parameter that represents the ratio of the diffusion time (the time
      it takes tau to diffuse from the axon hillock to the axon tip) to the half-life
      of tau. We also developed a model based on the hypothesis that tau is actively
      transported. Analytical solutions for some special situations were obtained. The
      model predictions were compared with experimentally measured tau distributions in
      axons reported in Black et al. (1996, J. Neurosc., 16: , 3601-3619), and based on
      these comparisons, we discussed the performance of various models. We
      demonstrated the significance of modulation of the tau attachment rate to MTs in
      the diffusion-reaction model. On the other hand, the active transport model
      predictions were consistent with experimental data even with constant kinetic
      rates. For short axons (up to 600 MUm in length) the predicted average transport
      velocity of tau was in the experimentally reported range for both the diffusion
      reaction and active transport models, but for the active transport model the
      average tau velocity was larger. 

PMID- 24573190
TI  - European Board Examination in Emergency Medicine (EBEEM): assessment of
      excellence.

PMID- 24573184
TI  - Estradiol, but not testosterone, heightens cortisol-mediated negative feedback on
      pulsatile ACTH secretion and ACTH approximate entropy in unstressed older men and
      women.
AB  - How sex steroids modulate glucocorticoid feedback on the hypothalamic-pituitary
      corticotrope (HPC) unit is controversial in humans. We postulated that
      testosterone (T) in men and estradiol (E2) in women govern unstressed cortisol
      mediated negative feedback on ACTH secretion. To test this hypothesis, 24 men and
      24 women age 58 +/- 2.4 yr were pretreated with leuprolide and either sex steroid
      (E2 in women, T in men) or placebo addback. Placebo or ketoconazole (KTCZ) was
      administered overnight to inhibit adrenal steroidogenesis during overnight 14-h
      intravenous infusions of saline or cortisol in a continuous versus pulsatile
      manner to test for feedback differences. ACTH was measured every 10 min during
      the last 8 h of the infusions. The main outcome measures were mean ACTH
      concentrations, pulsatile ACTH secretion, and ACTH approximate entropy (ApEn).
      ACTH concentrations were lower in women than men (P < 0.01), and in women in the
      E2+ compared with E2- group under both continuous (P = 0.01) and pulsatile (P =
      0.006) cortisol feedback, despite higher cortisol binding globulin and lower free
      cortisol levels in women than men (P < 0.01). In the combined groups, under both
      modes of cortisol addback, ACTH concentrations, pulsatile ACTH secretion, and
      ACTH secretory-burst mass correlated negatively and univariately with E2 levels
      (each P < 0.005). E2 also suppressed ACTH ApEn (process randomness) during
      continuous cortisol feedback (P = 0.004). T had no univariate effect but was a
      positive correlate of ACTH when assessed jointly with E2 (negative) under
      cortisol pulses. In conclusion, sex steroids modulate selective gender-related
      hypothalamic-pituitary adrenal-axis adaptations to cortisol feedback in
      unstressed humans. 

PMID- 24573187
TI  - Apelin-13 stimulates angiogenesis by promoting cross-talk between AMP-activated
      protein kinase and Akt signaling in myocardial microvascular endothelial cells.
AB  - Currently, there is major interest in the functions of apelin-13, an endogenous
      ligand for the orphan G-protein coupled receptor APJ, a receptor that closely
      resembles the angiotensin receptor AT1. In the present study, the role of apelin
      13 in angiogenesis and its mechanism as a novel angiogenic factor in myocardial
      microvascular endothelial cells (MMVECs) was investigated. It was revealed that
      apelin-13 can promote proliferation, migration and tube formation in MMVECs. In
      addition, apelin-13 dose dependently stimulated the phosphorylation of AMP
      activated protein kinase (AMPK) and endothelial nitric oxide synthase (eNOS) at
      Thr-172 and Ser-1179, respectively. The treatment with the AMPK (compound C) and
      protein kinase Akt/protein kinase B (Akt; LY294002) inhibitor significantly
      suppressed the apelin-13-induced AMPK, Akt and eNOS phosphorylation. They also
      inhibited the apelin13-stimulated endothelial cell migration and tube formation.
      Therefore, we hypothesize that apelin-13 promotes angiogenesis through the
      modulation of AMPK and Akt signaling in MMVECs.

PMID- 24573191
TI  - Impact of professional quality management on interdisciplinary emergency care
      units.
AB  - OBJECTIVES: In emergency departments (EDs), overcrowding, workload complexity,
      and cost containment represent current operational problems. In this
      retrospective observational study, we analyzed the effects of a professional
      quality management (QM) system on patient flow, diagnostic validity, and hospital
      costs. MATERIALS AND METHODS: In 2005/2006, the main ED at the University Medical
      Center Goettingen was reorganized. A professional QM system according to DIN EN
      ISO 9001:2008 was introduced in 2008. In a retrospective observational study, we
      compared the number of cases, the spectrum of clinical diagnoses, the validity of
      diagnoses, and hospital costs in the ED before (2005) and 2 years after the
      introduction of the QM system (2010). RESULTS: In the ED at the University
      Medical Center Goettingen, the number of cases increased by 22.7% between 2005
      and 2010. After the introduction of the QM system, a significant reduction in
      patients' length of stay within the ED was achieved (P<0.001). Furthermore, the
      rate of diagnostic errors for patients assigned for admission within the ED could
      be reduced significantly (P=0.002). A reduction of patient-related hospital costs
      of 8.9% was achieved by restriction of diagnostic tests according to standard
      operating procedures for each emergency diagnosis. CONCLUSION: The introduction
      of a professional QM system in EDs improves patient flow as well as quality of
      medical care and results in a significant reduction in hospital costs. Further
      analyses should evaluate the effects of QM on quality indicators in a prospective
      multicenter study. Validation of results has to be performed in a dynamic model
      for process simulation.

PMID- 24573192
TI  - Intubation by paramedics using the intubating laryngeal mask or AirTraq, King
      Vision, and Macintosh laryngoscopes in vehicle-entrapped patients: a manikin
      study.

PMID- 24573193
TI  - Capability of emergency departments to provide physician-based prehospital
      critical care teams.

PMID- 24573183
TI  - Remembering to eat: hippocampal regulation of meal onset.
AB  - A wide variety of species, including vertebrate and invertebrates, consume food
      in bouts (i.e., meals). Decades of research suggest that different mechanisms
      regulate meal initiation (when to start eating) versus meal termination (how much
      to eat in a meal, also known as satiety). There is a very limited understanding
      of the mechanisms that regulate meal onset and the duration of the postprandial
      intermeal interval (ppIMI). In the present review, we examine issues involved in
      measuring meal onset and some of the limited available evidence regarding how it
      is regulated. Then, we describe our recent work indicating that dorsal
      hippocampal neurons inhibit meal onset during the ppIMI and describe the
      processes that may be involved in this. We also synthesize recent evidence,
      including evidence from our laboratory, suggesting that overeating impairs
      hippocampal functioning and that impaired hippocampal functioning, in turn,
      contributes to the development and/or maintenance of diet-induced obesity.
      Finally, we identify critical questions and challenges for future research
      investigating neural controls of meal onset.

PMID- 24573194
TI  - Author response.

PMID- 24573195
TI  - A decision support system for the treatment of patients with ventricular assist
      device support.
AB  - BACKGROUND: Heart failure (HF) is affecting millions of people every year and it
      is characterized by impaired ventricular performance, exercise intolerance and
      shortened life expectancy. Despite significant advancements in drug therapy,
      mortality of the disease remains excessively high, as heart transplant remains
      the gold standard treatment for end-stage HF when no contraindications subsist.
      Traditionally, implanted Ventricular Assist Devices (VADs) have been employed in
      order to provide circulatory support to patients who cannot survive the waiting
      time to transplantation, reducing the workload imposed on the heart. In many
      cases that process could recover its contractility performance. OBJECTIVES: The
      SensorART platform focuses on the management and remote treatment of patients
      suffering from HF. It provides an interoperable, extendable and VAD-independent
      solution, which incorporates various hardware and software components in a
      holistic approach, in order to improve the quality of the patients' treatment and
      the workflow of the specialists. This paper focuses on the description and
      analysis of Specialist's Decision Support System (SDSS), an innovative component
      of the SensorART platform. METHODS: The SDSS is a Web-based tool that assists
      specialists on designing the therapy plan for their patients before and after VAD
      implantation, analyzing patients' data, extracting new knowledge, and making
      informative decisions. RESULTS: SDSS offers support to medical and VAD experts
      through the different phases of VAD therapy, incorporating several tools covering
      all related fields; Statistics, Association Rules, Monitoring, Treatment,
      Weaning, Speed and Suction Detection. CONCLUSIONS: SDSS and its modules have been
      tested in a number of patients and the results are encouraging.

PMID- 24573196
TI  - A possible origin of emerged HIV-1 after interrupting anti-retroviral therapy.
AB  - Although HIV-1 can be successfully eradicated from the circulating blood of HIV-1
      infected individuals using anti-retroviral therapy (ART), HIV-1 virions emerge
      immediately after the interruption of ART. This study was aimed to investigate
      the origin of the emerged HIV-1. After obtaining informed consent, blood samples
      from nine HIV-1-infected individuals and endoscopic ileum samples from five of
      the individuals were obtained. Purified peripheral mononuclear cells (PBMCs)and
      ileum cells were analyzed by flow-cytometry, and the V3 loop sequences of the HIV
      1 envelope protein were determined. By comparing the V3 loop sequences of the
      samples, we confirmed that the provirus hidden in the CD4(+) PBMCs was not the
      source of the HIV-1 that emerged after the interruption of ART. Although free
      virus and HIV-1-p24 antigen (p24)-positive cells were not seen in the blood of
      patients receiving ART, proviral DNA and p24 could be detected in the ileum from
      the same patient. Among the HIV-1-infected CD4(+) cells in the ileum samples,
      Valpha24(+) natural killer T (NKT) cells were the major p24-positive cells. These
      results suggest that the innate NKTcells in the mucosal compartment are the most
      likely candidates for the origin of the HIV-1 that emerged after ART was
      interrupted.

PMID- 24573197
TI  - Role of type I- and type II-interferon in expression of melanoma differentiation
      associated gene-5 in HSC-3 oral squamous carcinoma cells.
AB  - Melanoma differentiation-associated gene 5 (MDA-5) and retinoic acid-inducible
      gene-I (RIG-I)are members of DExH family of proteins, and known to play important
      roles in antiviral responses to induce type I interferons (IFNs). MDA-5 has been
      thought to sense RNA virus with long(>1 kb) double-stranded RNA. However, MDA-5
      is also induced by type II IFN that is involved in acquired immunity, suggesting
      that role of MDA-5 remains to be elucidated. In addition, no study regarding MDA
      5 in oral region has been performed. Here we investigated the role of MDA-5 in
      HCS-3 squamous carcinoma cells derived from oral epithelial cells. Treatment of
      HCS-3 cells with IFN-alpha2b or IFN-gamma significantly induced MDA-5 as well as
      RIG-I. IFN-alpha2b exerted anti-proliferative effect in HSC-3 cells while no such
      effect was observed in the cells treated with IFN-gamma. MDA-5 is known to be
      associated with tumor cell growth in melanoma. However, overexpression of MDA-5
      did not alter the proliferation in HSC-3 cells, indicating that MDA-5 is
      unrelated to the cell growth in this type of cells. We conclude that MDA-5 is
      induced by both type I- and type II-IFNs in HSC-3 cells, and this suggests MDA-5
      may play a role in immune responses in oral cavity.

PMID- 24573198
TI  - Synergistic effects of loxoprofen and glycine on the micturition reflex in
      conscious rats.
AB  - We examined the inhibitory effects of loxoprofen, a cyclooxygenase inhibitor, and
      glycine, a major inhibitory neurotransmitter, on the micturition reflex in
      conscious rats and hypothesized that these drugs would interact synergistically
      to inhibit micturition. Voiding behaviors were assessed using a metabolic cage.
      Oral loxoprofen decreased the urinary frequency, and only a high dose(10 mg/kg)
      significantly reduced the voided volume. With cystometry, intravenous
      loxoprofen(0.1-3 mg/kg) and glycine (30 and 100 mg/kg) prolonged the
      intercontraction intervals (ICI) in adose-dependent manner, but did not change
      the maximum voiding pressure (MVP) in conscious rats. The combination of
      loxoprofen (3 mg/kg) and glycine (100 mg/kg) strongly prolonged the ICI more than
      with either drug alone. The lowest dose of loxoprofen (0.1 mg/kg) and glycine(30
      mg/kg) did not affect either the ICI or the MVP, but their combination resulted
      in a significant increase in the ICI. These results suggest that the combined
      administration of loxoprofen and glycine produced a synergistic inhibitory effect
      on the micturition reflex.

PMID- 24573199
TI  - Detection of tumor-associated antigens in culture supernatants using
      autoantibodies in sera from patients with bladder cancer.
AB  - Secreted proteins play essential roles in the process of tumorigenesis, and the
      analysis of tumor-secreted proteins has been suggested as a promising strategy
      for identifying cancer biomarkers. In this study, we performed proteomic analysis
      to identify proteins secreted from bladder cancer cell lines that are recognized
      by autoantibodies in sera from patients with bladder cancer. In
      addition,autoantibodies against the identified proteins were validated using a
      dot-blot array with sera from patients with bladder cancer and normal controls.
      As the results, we detected twenty-five and thirty-two immunoreactive spots in
      sera from patients with high- and low-grade bladder cancer, respectively.In
      addition, validation analysis revealed that serum IgG levels of anti-calreticulin
      and matrix metalloproteinase-2 (MMP2) autoantibodies were significantly higher in
      bladder cancer patients than in normal controls (both P < 0.05). Furthermore, the
      serum IgG level of anti-MMP2 autoantibody was significantly higher in patients
      with high- compared to low-grade bladder cancer(P < 0.05). On multivariate
      analysis, the serum IgG level of anti-MMP2 autoantibody was an independent
      predictor of cancer-specific survival (P < 0.05). Based on these findings, serum
      IgG levels of anti-calreticulin and MMP2 autoantibodies may be novel biomarker
      candidates for bladder cancer and its clinical outcome.

PMID- 24573200
TI  - Three types of macrophagic cells in the mesentery of mice with special reference
      to LYVE-1-immunoreactive cells.
AB  - Immunohistochemistry using whole mount preparations of the murine mesentery
      revealed two types of LYVE-1-immunoreactive cells with dendritic morphology other
      than F4/80(+) typical macrophages.The two types of LYVE-1(+) cells were regularly
      distributed with constant intervals throughout the mesentery and appeared to
      possess their own territory. Both types of LYVE-1(+) cells were weakly or
      moderately immunopositive for F4/80 antibody, a marker of macrophages,while
      F4/80(+) round macrophages were absolutely free from the LYVE-1 immunoreactivity.
      Only macrophages could ingest latex particles of 20 nm in diameter 3 h after a
      peritoneal injection.Peritoneal administration of lipopolysaccharide (LPS)
      induced a rapid reduction of LYVE-1 immunoreactivity in the cells with dendritic
      morphology followed by an increased immunoreactivity to F4/80 antibody, and
      simultaneously by dynamic changes in their shape. Under normal
      conditions,F4/80(+) macrophages in various connective tissues expressed LYVE-1,
      in contrast to lack of LYVE-1 in F4/80(+) macrophages within the parenchyma of
      visceral organs and macrophages residing in hepatic sinusoids and pulmonary
      alveoli. LYVE-1 may play a role in cell adhesion and migration of macrophagic
      cells within connective tissues rich in hyaluronan, and loss of LYVE-1 becomes a
      reliable sign of activated conditions in inflammation.

PMID- 24573201
TI  - Purification of the goldfish membrane progestin receptor alpha (mPRalpha)
      expressed in yeast Pichia pastoris.
AB  - Membrane progestin receptors (mPRs) are key mediators of rapid, nongenomic
      actions of progestins on plasma membranes. We established a procedure for the
      expression and purification of recombinant goldfish mPRalpha using the
      methylotropic yeast Pichia pastoris. In P. pastoris, the recombinant protein,
      which carried C-terminal histidine and c-Myc tags, was expressed in an active
      form as the receptor for maturation-inducing steroids of fish. Expressed proteins
      were bound reversibly with a high affinity (Kd = 9.4 nM) at a single binding site
      that could be saturated. After solubilization of mPRalpha with n-dodecyl-beta-D
      maltoside (DDM) from yeast membranes, the recombinant protein was purified using
      three different columns: first it was affinity-purified over nickel
      nitrilotriaceticacid (Ni-NTA), then bound to a cellulose resin with free amino
      groups and finally to a column with affinity for the c-Myc epitope. The identity
      of the purified protein was verified by MALDI-TOF/MS analysis and its capacity to
      bind progestin remained. Expression and purification of mPRalpha protein in its
      functional form will enable the screening of ligands and the determination of its
      three dimensional structure.

PMID- 24573202
TI  - Expression of mRNAs for the diacylglycerol kinase family in immune cells during
      an inflammatory reaction.
AB  - Phosphoinositide metabolism is intimately involved in cellular signal
      transduction. In response to extracellular stimuli, it generates diacylglycerol
      (DG), which serves as a lipid second messenger molecule to activate various
      proteins in various organs under pathophysiological conditions.
      Diacylglycerolkinase (DGK) constitutes an enzyme family that catalyzes conversion
      of DG to phosphatidic acid. It is therefore regarded as a regulator of the DG
      signal. Previous studies have revealed the critical role of alpha and zeta types
      of DGK in T cell functions. Nevertheless, little is known about the expression
      patterns of the DGK family in immune cells of various kinds. After examination of
      the expression profile of DGK isozymes in immune cells that are isolated from
      human blood, we investigated whether their mRNA expression levels would be
      changed during an inflammatory reaction. Results showed that DGK isozyme mRNAs
      are widely expressed in immune cells, except for DGKbeta and DGKiota. During an
      inflammatory reaction, DGKepsilon mRNA was increased transiently in the initial
      phase (20-40 min) of stimulation with both LPS and IL-2 in T cell-derived HUT-102
      cells and macrophage-derived RAW264 cells. At the organismal level, an
      intraperitoneal injection of LPS also induced upregulation of DGKepsilon mRNA in
      the spleen in a similar,but not identical, manner. These results suggest that
      DGKepsilon is involved in inflammatory processes of the cellular immune system.

PMID- 24573203
TI  - Periosteum-derived cells respond to mechanical stretch and activate Wnt and BMP
      signaling pathways.
AB  - The periosteum supplies osteoblasts and nutrients for bone metabolism and is
      important for osteoblast differentiation and osteogenesis. Recently, periosteum
      derived cells have been used for orofacial bone regeneration therapy. However,
      little is known about the function of the periosteum in physiological bone
      remodeling. On our hypothesis that the periosteum senses a mechanical stress to
      induce bone remodeling, we subjected human jaw bone periosteum cells (HJBPCs) to
      uniaxial stretching for 24 h and characterized their gene expression profiles by
      microarray analysis. Of62,976 genes detected, 550 genes related to bone
      metabolism were extracted, and 76 of these genes with large changes in gene
      expression were short-listed. The results indicated that mechanical stretch in
      HJBPCs regulated the expression levels of genes involved in the Wingless-type
      MMTV integration (Wnt) site, bone morphogenetic protein (BMP) signaling pathways,
      and inflammatory cytokines. We propose that periosteum-derived cells sense
      mechanical stress and then activate and regulate signals for osteoblast
      differentiation and osteogenesis.

PMID- 24573204
TI  - Serotonergic modulation of inhibitory synaptic transmission in mouse inferior
      colliculus.
AB  - The inferior colliculus (IC) transmits the ascending auditory signal to the
      thalamic medial geniculate nucleus. Previous studies have reported that
      serotonergic input originating from the raphe nuclei has a strong influence on
      signal processing within the central nucleus of the IC. To identify the cellular
      target for the serotonergic modulation in the IC, we examined the effect of
      serotonin as well as selective serotonin reuptake inhibitor (SSRI) fluvoxamine on
      spontaneous GABAergic and glycinergic inhibitory postsynaptic currents (sIPSCs)
      recorded with whole-cell recordings.Consistent with earlier studies, we confirmed
      that serotonin robustly enhanced the frequency, but not amplitude, of GABAergic
      sIPSCs. It should be noted that the application of fluvoxamine alone marginally
      increased the frequency of GABAergic sIPSCs. These findings suggest that
      serotonin is endogenously released even in slice preparations, and it negatively
      modulates the tone of activity of inhibitory neurons within IC. We also examined
      the effect of serotonin and fluvoxamine on glycinergic sIPSCs and found that
      serotonin has a significantly weaker effect on glycinergic sIPSCs than on
      GABAergic sIPSCs. The differential sensitivity of the GABAergic and glycinergic
      sIPSCs to serotonin implies that serotonergic input plays a specific role in
      auditory information processing.Moreover, it suggests that the serotonergic input
      may contribute to pathological conditions such as tinnitus.

PMID- 24573205
TI  - Expression of a monocarboxylate transporter in reticular cells of the mouse lymph
      node and its involvement in the uptake of exogenous particles.
AB  - The monocarboxylate transporter (MCT)-1 plays an important role in the transfer
      of monocarboxylate metabolites such as lactate, ketone bodies, and acetic acid.
      The present study revealed the selective localization of MCT1 in reticular cells
      of the murine lymph node. An intense MCT1 immunoreactivity was found in the
      reticular cells forming a cellular network together with sinus-lining cells in
      the medullary sinuses and in cells covering the inside of subcapsular
      sinuses.Electron-microscopically, MCT1 was localized along the plasma membrane of
      the reticular cells.The medullary reticular cells vigorously ingested carboxylate
      modified latex particles, but any reticular cells within the cortical lymphoid
      follicles and medullary cords neither expressed MCT1 nor incorporated latex
      particles. MCT1-immunoreactive reticular cells also expressed LYVE-1,which is a
      hyaluronan receptor abundant in both the lymphatic endothelium and hepatic
      sinusoidal epithelium. The selective localization of MCT1 and LYVE-1 suggests a
      high level of activity for lymphoid reticular cells in the uptake of carboxylate
      modified and hyaluronate waste substances circulating in the body.

PMID- 24573208
TI  - Severe intraventricular hemorrhage in a new decade: what do we tell parents?

PMID- 24573209
TI  - Development of care in the NICU.

PMID- 24573206
TI  - Cardiomyocyte-specific transforming growth factor beta suppression blocks
      neutrophil infiltration, augments multiple cytoprotective cascades, and reduces
      early mortality after myocardial infarction.
AB  - RATIONALE: Wound healing after myocardial infarction involves a highly regulated
      inflammatory response that is initiated by the appearance of neutrophils to clear
      out dead cells and matrix debris. Neutrophil infiltration is controlled by
      multiple secreted factors, including the master regulator transforming growth
      factor beta (TGFbeta). Broad inhibition of TGFbeta early postinfarction has
      worsened post-myocardial infarction remodeling; however, this signaling displays
      potent cell specificity, and targeted suppression particularly in the myocyte
      could be beneficial. OBJECTIVE: Our aims were to test the hypothesis that
      targeted suppression of myocyte TGFbeta signaling ameliorates postinfarct
      remodeling and inflammatory modulation and to identify mechanisms by which this
      may be achieved. METHODS AND RESULTS: Mice with TGFbeta receptor-coupled
      signaling genetically suppressed only in cardiac myocytes (conditional TGFbeta
      receptor 1 or 2 knockout) displayed marked declines in neutrophil recruitment and
      accompanying metalloproteinase 9 activation after infarction and were protected
      against early-onset mortality due to wall rupture. This is a cell-specific
      effect, because broader inhibition of TGFbeta signaling led to 100% early
      mortality due to rupture. Rather than by altering fibrosis or reducing the
      generation of proinflammatory cytokines/chemokines, myocyte-selective TGFbeta
      inhibition augmented the synthesis of a constellation of highly protective
      cardiokines. These included thrombospondin 4 with associated endoplasmic
      reticulum stress responses, interleukin-33, follistatin-like 1, and growth and
      differentiation factor 15, which is an inhibitor of neutrophil integrin
      activation and tissue migration. CONCLUSIONS: These data reveal a novel role of
      myocyte TGFbeta signaling as a potent regulator of protective cardiokine and
      neutrophil-mediated infarct remodeling.

PMID- 24573210
TI  - Spontaneous thrombosis of the abdominal aorta in two neonates.
AB  - Although relatively rare, thromboembolic events are a major complication of
      invasive procedures, mainly vascular catheterization, required for the survival
      of neonates admitted to the neonatal intensive care unit. Sometimes symptoms may
      be ambiguous and the diagnosis may not be immediate. The clinical relevance of
      polymorphism of methilene tetrahydrofolate reductase (MTHFR) gene heterozigosity
      and of omocystein level in the genesis of these thromboembolic events are poorly
      understood. We report two cases of thrombosis of the abdominal aorta, mimicking
      aortic coarctation, in two neonates, successfully treated at diagnosis with 170
      UI/Kg of low molecular weight heparin (LMWH) twice daily, without side effects.
      Screening for prothrombotic defects revealed the heterozygosity for MTHFR C677T
      in both neonates and low omocystein level in one of them. We suggest that in
      newborns vascular thrombosis should be considered in the differential diagnosis
      of acute disorders of blood circulation at birth and familial thrombophilia
      should be investigated. LMWH therapy with a dose of 170 UI/Kg twice daily usually
      allows vascular recanalization, without side effects. 

PMID- 24573211
TI  - Hypertrophic intraventricular flow obstruction after very-low-dose dexamethasone
      (Minidex) in preterm infants: case presentation and review of the literature.
AB  - The use of dexamethasone in preterm infants developing bronchopulmonary dysplasia
      has been proven to be effective. Hypertrophic cardiomyopathy is a frequently
      reported, although transient, side effect of high-dose dexamethasone
      administration. The recent introduction of very low dexamethasone dose, called
      'Minidex', promised equal effectiveness compared to high-dose dexamethasone
      without relevant side effects. Our study presents two patients developing
      hypertrophic cardiomyopathy with intraventricular cardiac obstruction after
      administration of 'Minidex'. Marked cardiac side effects may occur even during
      very-low-dose dexamethasone treatment in preterm neonates. Betablocker and
      discontinuation of dexamethasone seem to allow spontaneous reversal of myocardial
      hypertrophy and obstruction. After all, systematic surveys of the incidence of
      cardiac complications in a larger population of preterm infants treated with very
      low doses of dexamethasone are needed. 

PMID- 24573212
TI  - Hyperinsulinemia has prominent role in refeeding syndrome pathophysiology.

PMID- 24573213
TI  - Transient hyperinsulinemia may be responsible from electrolyte abnormalities of
      refeeding syndrome seen in very low birth weight infants with intrauterine growth
      restriction.

PMID- 24573214
TI  - Sulfur and iron accumulation in three marine-archaeological shipwrecks in the
      Baltic Sea: the Ghost, the Crown and the Sword.
AB  - Sulfur and iron concentrations in wood from three 17(th) century shipwrecks in
      the Baltic Sea, the Ghost wreck, the Crown and the Sword, were obtained by X-ray
      fluorescence (XRF) scanning. In near anaerobic environments symbiotic
      microorganisms degrade waterlogged wood, reduce sulfate and promote accumulation
      of low-valent sulfur compounds, as previously found for the famous wrecks of the
      Vasa and Mary Rose. Sulfur K-edge X-ray absorption near-edge structure (XANES)
      analyses of Ghost wreck wood show that organic thiols and disulfides dominate,
      together with elemental sulfur probably generated by sulfur-oxidizing Beggiatoa
      bacteria. Iron sulfides were not detected, consistent with the relatively low
      iron concentration in the wood. In a museum climate with high atmospheric
      humidity oxidation processes, especially of iron sulfides formed in the presence
      of corroding iron, may induce post-conservation wood degradation. Subject to more
      general confirmation by further analyses no severe conservation concerns are
      expected for the Ghost wreck wood. 

PMID- 24573215
TI  - Effect of PEG-mediated pore forming on Ca-alginate immobilization of nitrilase
      producing bacteria Pseudomonas putida XY4.
AB  - Effect of PEG-mediated pore forming on Ca-alginate immobilization of nitrilase
      producing bacteria Pseudomonas putida XY4 was studied. Through using PEG as
      porogen, the environmental tolerance as well as the biocatalytic reaction
      efficiency of immobilized cells was greatly improved, i.e., Ca-alginate-PEG
      immobilized cells got better temperature and substrate concentration tolerance
      than Ca-alginate immobilized cells and showed similar efficiency with free cells,
      suggesting that the intrinsic mass transfer resistance of immobilization
      obviously decreased. It was also observed that the pore diameter and porosity of
      immobilization beads were related with the molecular weight of PEG. PEG400 was
      found to be a relatively suitable porogen for Ca-alginate-PEG immobilized cells
      catalyzed hydrolysis of glycinonitrile. It was noteworthy that the Ca-alginate
      PEG immobilized cells could be reused more than 18 times with little loss of
      enzyme activity which had shown good operation ability and great application
      potential. 

PMID- 24573216
TI  - Growth conditions of clostridium perfringens type B for production of toxins used
      to obtain veterinary vaccines.
AB  - The diseases caused for Clostridium perfringens are generically called
      enterotoxemias because toxins produced in the intestine may be absorbed into the
      general circulation. C. perfringens type B, grown in batch fermentation, produced
      toxins used to obtain veterinary vaccines. Glucose in concentrations of 1.4-111.1
      mM was used to define the culture medium. The minimum concentration for a
      satisfactory production of vaccines against clostridial diseases was 55.6 mM.
      Best results were brought forth by meat and casein peptones, both in the
      concentration 5.0 g l(-1) in combination with glucose and a culture pH maintained
      at 6.5 throughout the fermentation process. The production of lactic, acetic and
      propionic organic acids was observed. Ethanol was the metabolite produced in the
      highest concentration when cultures maintained steady pH of 6.5 with exception of
      cultures with initial glucose concentration of 1.4 mM, where the highest
      production was of propionic acid. Maximal cell concentration and the highest
      toxin title concomitantly low yield coefficient to organic acids and ethanol were
      obtained using basal medium containing 111.1 mM glucose under a controlled pH
      culture (pH) 6.5 in batch fermentations of C. perfringens type B. These data
      contribute to improve process for industrial toxin production allowing better
      condition to produce a toxoid vaccine. 

PMID- 24573217
TI  - Exponential model describing methane production kinetics in batch anaerobic
      digestion: a tool for evaluation of biochemical methane potential assays.
AB  - Biochemical methane potential assays, usually run in batch mode, are performed by
      numerous laboratories to characterize the anaerobic degradability of biogas
      substrates such as energy crops, agricultural residues, and organic wastes.
      Unfortunately, the data obtained from these assays lacks common, universal bases
      for comparison, because standard protocols did not diffuse to the entire
      scientific community. Results are usually provided as final values of the methane
      yields of substrates. However, methane production curves generated in these
      assays also provide useful information about substrate degradation kinetics,
      which is rarely exploited. A basic understanding of the kinetics of the biogas
      process may be a first step towards a convergence of the assay methodologies on
      an international level. Following this assumption, a modeling toolbox containing
      an exponential model adjusted with a simple data-fitting method has been
      developed. This model should allow (a) quality control of the assays according to
      the goodness of fit of the model onto data series generated from the digestion of
      standard substrates, (b) interpretation of substrate degradation kinetics, and
      (c) estimate of the ultimate methane yield at infinite time. The exponential
      model is based on two assumptions: (a) the biogas process is a two-step reaction
      yielding VFA as intermediate products, and methane as the final product, and (b)
      the digestible substrate can be divided into a rapidly degradable and a slowly
      degradable fraction. 

PMID- 24573218
TI  - Evidence for natural Borna disease virus infection in healthy domestic animals in
      three areas of western China.
AB  - Borna disease virus (BDV) is a non-cytolytic, neurotropic RNA virus that can
      infect many vertebrate species, including humans. To date, BDV infection has been
      reported in a range of animal species across a broad global geographic
      distribution. However, a systematic epidemiological survey of BDV infection in
      domesticated animals in China has yet to be performed. In current study, BDV RNA
      and antibodies in 2353 blood samples from apparently healthy animals of eight
      species (horse, donkey, dog, pig, rabbit, cattle, goat, sheep) from three areas
      in western China (Xinjiang province, Chongqing municipality, and Ningxia
      province) were assayed using reverse transcription qPCR (RT-qPCR) and ELISA
      assay. Brain tissue samples from a portion of the BDV RNA- and/or antibody
      positive animals were subjected to RT-qPCR and western blotting. As a result,
      varying prevalence of BDV antibodies and/or RNA was demonstrated in various
      animal species from three areas, ranging from 4.4 % to 20.0 %. Detection of BDV
      RNA and/or antibodies in Chongqing pigs (9.2 %) provided the first known evidence
      of BDV infection in this species. Not all brain tissue samples from animals whose
      blood was BDV RNA and/or antibody positive contained BDV RNA and protein. This
      study provides evidence that BDV infection among healthy domestic animal species
      is more widespread in western China than previously believed.

PMID- 24573219
TI  - The complete genome sequence of a European goose reovirus strain.
AB  - The complete genomic sequence of a Hungarian goose orthoreovirus strain (D20/99)
      is reported in this study. The genome of D20/99 is 22,969 bp in length (range,
      3958 bp for L1 to 1124 bp for S4) and encodes 11 putative proteins. Pairwise
      sequence comparisons and phylogenetic analyses indicated that D20/99 shares
      genetic signatures with some contemporary Chinese duck and goose reovirus
      strains, except for the MUA, MUNS and sigmaA protein coding genes, which
      represented independent genetic lineages. This study implies a greater genetic
      diversity among waterfowl-origin orthoreoviruses than hitherto recognized.

PMID- 24573220
TI  - Comparing the effect of Toll-like receptor agonist adjuvants on the efficiency of
      a DNA vaccine.
AB  - We have investigated whether poly(I:C) Toll-like receptor 3 (TLR3) and resiquimod
      Toll-like receptor 7 (TLR7) agonists can serve as vaccine adjuvants and promote
      the efficiency of therapeutic DNA vaccination against tumors expressing the human
      papilloma virus 16 (HPV-16) E7 protein. For this purpose, C57BL/6 mice were
      inoculated with 2 * 10(5) TC-1 cells, and they were then immunized with HPV-16 E7
      DNA vaccine alone or with 50 MUg of resiquimod or poly(I:C) individually. We
      found that poly(I:C) and resiquimod could induce more antigen-specific lymphocyte
      proliferation and cytolytic activity compared to vaccination with E7 DNA alone.
      While E7 DNA had no significant inhibitory effect on tumor growth, co
      administration of poly(I:C) and resiquimod with E7 DNA induced significant tumor
      regression. Peripheral and local cytokine assays demonstrated that co
      administration of poly(I:C) and resiquimod with E7 DNA induced circulating
      antigen-specific IFN-gamma and nonspecific intratumoral IL-12. TLR3 and TLR7
      agonists can be used to enhance the immune response to DNA vaccine immunogens.
      Taken together, these data indicate that combined vaccination with DNA encoding
      HPV-16 E7 plus TLR agonists provides a strategy for improving the efficacy of a
      vaccine as a possible immunotherapeutic strategy for cervical cancer.

PMID- 24573222
TI  - 1,25-Dihydroxyvitamin D3 and cisplatin synergistically induce apoptosis and cell
      cycle arrest in gastric cancer cells.
AB  - 1,25-Dihydroxyvitamin D3 [1,25(OH)2D3] plays an anticancer role in multiple types
      of cancer and potentiates the cytotoxic effects of several common
      chemotherapeutic agents. The hypercalcemia caused by 1,25(OH)2D3 alone or
      resistance to cisplatin weaken the anticancer effects of vitamin D. Thus, in this
      study, we aimed to investigate the synergistic effects of 1,25(OH)2D3 and
      cisplatin on the apoptosis and cell cycle progression of gastric cancer cells.
      BGC-823 human gastric cancer cells were treated with 1,25(OH)2D3 or cisplatin
      alone, or a combination of both agents. Cell apoptosis was assessed by TUNEL
      assay and flow cytometry. The expression of the apoptosis-related proteins,
      poly(ADP-ribose) polymerase (PARP), Bax, Bcl-2, caspase-3 and caspase-8, was
      examined using immunoblot analysis. ERK and AKT phosphorylation were examined by
      immunoblot analysis. The cell cycle distribution was determined by propidium
      iodide staining and flow cytometric analysis. p21 and p27 protein expression was
      also examined using immunoblot analysis. Our results revealed that co-treatment
      with 1,25(OH)2D3 enhanced cisplatin-induced apoptosis and upregulated the
      expression of Bax, and promoted the cleavage of PARP and caspase-3. The
      phosphorylation levels of ERK and AKT were reduced following combined treatment
      with 1,25(OH)2D3 and cisplatin. The percentage of cells in the G0/G1 phase was
      greater in the cells treated with the combined treatment than in those treated
      with either 1,25(OH)2D3 or cisplatin alone. p21 and p27 expression was
      upregulated following co-treatment with both agents. The results of this study
      suggest that 1,25(OH)2D3 potentiates cisplatin-mediated cell growth inhibition
      and cell apoptosis, which involves the upregulation of Bax, a decrease in ERK and
      AKT phosphorylation levels, and increased p21 and p27 levels.

PMID- 24573223
TI  - A telemonitoring tool based on serious games addressing money management skills
      for people with intellectual disability.
AB  - This article presents a telemonitoring tool based on computer games, aimed at
      money management skill improvement for people with Intellectual Disabilities
      (ID). The presented tool is divided into two parts: on one hand, some training
      activities related to payments and currency discrimination based on Serious Games
      are proposed to the user using a multitouch device. On the other hand, the
      psychologists and specialist who work with them, can access to the Serious Games
      results using an online application in order to evaluate their evolution. The
      results are measured according to the number of errors they have during the
      proposed activities, the time they need to complete them and the score. The
      article show the results of an experiment made with a clinical sample of 12 users
      with ID between 12 and 15 years, taking into account that all of them are capable
      of correct oral communication and they do not have severe physical coordination
      problems. Only two users completed all the games without errors. Males obtained a
      mean of 28.25 errors, whereas females obtained a mean of 17.75. The results show
      significant difference between the selection of games 1, 2 or 3, because all of
      them prefer the game 1 related with "Payments" probably because it permits more
      interaction using the multitouch device. The authors also made a qualitative
      evaluation and the results have been very promising and satisfactory. 

PMID- 24573224
TI  - Comparative proteome analysis of the response of ramie under N, P and K
      deficiency.
AB  - Ramie is an important natural fiber. There has been little research on the
      molecular mechanisms of ramie related to the absorption, utilization and
      metabolism of nitrogen (N), phosphorus (P) and potassium (K). One approach to
      reveal the mechanisms of N, P and K (NPK) utilization and metabolism in ramie is
      comparative proteome analysis. The differentially expressed proteins in the
      leaves of ramie were analyzed by proteome analysis after 6 days of N- and K
      deficient treatments and 3 days of P-deficient treatment using MALDI-TOF/TOF mass
      spectrometry and 32, 27 and 51 differential proteins were obtained, respectively.
      These proteins were involved in photosynthesis, protein destination and storage,
      energy metabolism, primary metabolism, disease/defense, signal transduction, cell
      structure, transcription, secondary metabolism and protein synthesis. Ramie
      responded to NPK stress by enhancing secondary metabolism and reducing
      photosynthesis and energy metabolism to increase endurance. Specifically, ramie
      adapted to NPK deficiency by increasing signal transduction pathways, enhancing
      the connection between glycolysis and photosynthesis, promoting the intracellular
      flow of carbon and N; promoting the synthesis cysteine and related hormones and
      upregulating actin protein to promote growth of the root system. The experimental
      results provide important information for further study on the high-efficiency
      NPK utilization mechanism of ramie.

PMID- 24573226
TI  - Allelic methylation status of CpG islands on chromosome 21q in patients with
      Trisomy 21.
AB  - Trisomy 21 is a chromosomal condition caused by the presence of all or part of an
      extra 21st chromosome. There has been limited research into the DNA methylation
      status of CpG islands (CGIs) in trisomy 21, therefore, exploring the DNA
      methylation status of CGIs in 21q is essential for the development of a series of
      potential epigenetic biomarkers for prenatal screening of trisomy 21. First, DNA
      sequences of CGIs in 21q from the USCS database were obtained and 149 sequences
      and 148 pairs of primers in the BGI YH database were aligned. All 300 cases were
      analyzed by a heavy methyl-polymerase chain reaction (HM-PCR) assay and a
      comparison of the DNA methylation status of CGIs was made between trisomy 21 and
      the control. The HM-PCR assay results did not show a difference in the DNA
      methylation status between individuals with trisomy 21 and the control. In total,
      there were 11 CGIs that showed various DNA methylation statuses between Japanese
      and Chinese patients. Subsequently, bisulfite genomic sequencing found variations
      in the methylation status of CpG dinucleotides in CGIs (nos. 14, 75, 109, 134 and
      146) between trisomy 21 and the control. The different DNA methylation status of
      CpG dinucleotides in CGIs may be a potential epigenetic marker for diagnosing
      trisomy 21. No difference was identified in the DNA methylation status of 21q
      CGIs among Chinese individuals with trisomy 21 and the control. The homogeneity
      of the DNA methylation status of 21q CGIs in Chinese patients indicates that DNA
      methylation is likely to be an epigenetic marker distinguishing ethnicities.

PMID- 24573227
TI  - [Assessing the influence of reconstruction kernel in plaque imaging in computed
      tomography].
AB  - Plaque imaging using computed tomography (CT) is an important diagnostic method
      for predicting the risk of vascular events. However, the CT value variability of
      plaques, which depends on the scan parameters, remains a key challenge. The aim
      of this study was to evaluate the effect of reconstruction properties on the CT
      value, area, and shape reproducibility of plaques. In general, the types of
      reconstruction kernels in a CT system are limited, thus impeding the acquisition
      of the necessary resolution properties (modulation transfer functions: MTFs). We
      therefore obtained images with eight types (smoothed to edge-enhanced) of
      resolution property by applying frequency processing to the original CT images.
      We made phantoms of simulated 6-mm-diameter vessels with plaque and scanned them
      at different doses. The CT values, areas, and shape reproducibility of plaques
      were measured from each processed image. Enhanced-type resolution with no edge
      enhancement (not exceeding 1.0) effectively raised the CT value and shape
      reproducibility accuracies. However, edge-enhancement type resolution caused
      errors in the CT value, area and shape reproducibility. 

PMID- 24573225
TI  - Selection of candidate reference genes for real-time PCR studies in lettuce under
      abiotic stresses.
AB  - The process of selection and validation of reference genes is the first step in
      studies of gene expression by real-time quantitative polymerase chain reaction
      (RT-qPCR). The genome of lettuce, the most popular leaf vegetable cultivated
      worldwide, has recently been sequenced; therefore, suitable reference genes for
      reliable results in RT-qPCR analyses are required. In the present study, 17
      candidate reference genes were selected, and their expression stability in
      lettuce leaves under drought, salt, heavy metal, and UV-C irradiation conditions
      and under the application of abscisic acid (ABA) was evaluated using geNorm and
      NormFinder software. The candidate reference genes included protein-coding
      traditional and novel reference genes and microRNAs (miRNAs). The results
      indicate that the expression stability is dependent on the experimental
      conditions. The novel protein-coding reference genes were more suitable than the
      traditional reference genes under drought, UV-C irradiation, and heavy metal
      conditions and under the application of ABA. Only under salinity conditions were
      the traditional protein-coding reference genes more stable than the novel genes.
      In addition, the miRNAs, mainly MIR169, MIR171/170 and MIR172, were stably
      expressed under the abiotic stresses evaluated, representing a suitable
      alternative approach for gene expression data normalization. The expression of
      phenylalanine ammonia lyase (PAL) and 4-hydroxyphenylpyruvate dioxygenase (HPPD)
      was used to further confirm the validated protein-coding reference genes, and the
      expression of MIR172 and MIR398 was used to confirm the validated miRNA genes,
      showing that the use of an inappropriate reference gene induces erroneous
      results. This work is the first survey of the stability of reference genes in
      lettuce and provides guidelines to obtain more accurate RT-qPCR results in
      lettuce studies.

PMID- 24573228
TI  - [Research studies on independent verification of monitor units in radiation
      therapy].
AB  - To prevent the recurrence of irradiation accidents, monitor-unit (MU)
      verification that is independent of the MU values calculated using the radiation
      treatment planning system (RTPS) is required. In this study, we investigated
      whether independent verification of MU values is being conducted in medical
      settings and examined the types and methods used. Our results indicate that 93.8%
      of facilities conduct independent MU verification. The methods used vary
      according to the facility: 30.4% conduct actual measurements, 18.6% use MS-Excel
      calculation sheets, 16.7% use specialized commercially-available software, 14.7%
      use spreadsheets 13.7% use calculators, and 5.9% use other methods. In this
      study, we were able to formulate basic data that can be used for information
      sharing between facilities. 

PMID- 24573229
TI  - [Technical features and roles of cobalt-57 flood sources for daily quality
      control of gamma cameras].
AB  - Quality control (QC) detects changes in the performance of gamma cameras that
      could adversely affect interpretations of clinical studies. We used plate and
      sheet (57)Co flood sources to measure extrinsic uniformity during daily QC. Each
      source, when placed on the top of a collimated detector, allowed the acquisition
      of uniform images from both detectors, thus reducing the amount of time needed to
      perform daily QC. No serious problems with the gamma camera system were revealed
      by visual checks, and changes in detector sensitivity were rapidly determined by
      observing daily variations in the measured values of extrinsic uniformity.
      Furthermore, (57)Co flood sources confer advantages in that they shorten the time
      required for preparation of flood sources and reduce the consequent exposure of
      medical staff to radiation. 

PMID- 24573230
TI  - [Data quality and interpretation of analysis results].

PMID- 24573231
TI  - [Primitive assessment system for secondary neutron in the radiotherapy field].

PMID- 24573233
TI  - [Medical electrical equipment-part 2-54: particular requirements for the basic
      safety and essential performance of X-ray equipment for radiography and
      radioscopy, JIS Z 4751-2-54: 2012].

PMID- 24573232
TI  - [Strategy of how to take action for system of a radiation section in natural
      disasters and rolling blackouts].

PMID- 24573234
TI  - [Seeking proper medical payment system reward evaluation based on three
      guarantees (safety, precision and production)].

PMID- 24573235
TI  - [Upon the opening of 70th Annual Scientific Congress of the Japanese Society of
      Radiological Technology].

PMID- 24573236
TI  - miR-1236-3p represses the cell migration and invasion abilities by targeting ZEB1
      in high-grade serous ovarian carcinoma.
AB  - Ovarian cancer, particularly high-grade serous ovarian carcinoma (HG-SOC), is
      still the main cause of death among gynecological malignancies. However, the
      molecular mechanisms related to its malignant biological behavior are still
      unclear. Recent studies indicate that microRNAs (miRNAs) play an important role
      in tumor metastasis. Here, we report that miR-1236-3p expression was
      downregulated in HG-SOC when compared to that in normal fallopian tube tissue.
      Manipulation of miR-1236-3p significantly influenced the morphology, migration
      and invasion of ovarian cancer cell lines (A2780 and SKOV3). With dual-luciferase
      reporter assay, we demonstrated that miR-1236-3p binds to the 3'UTR of zinc
      finger E-box binding homeobox 1 (ZEB1) mRNA, and functions as a negative
      regulator of ZEB1. Furthermore, we revealed that manipulation of miR-1236-3p
      modulates ZEB1 expression and influences expression of its downstream genes E
      cadherin and N-cadherin at both the mRNA and protein levels. We also found an
      inverse relationship between miR-1236-3p and ZEB1 expression in the HG-SOC tissue
      samples. Taken together, our results indicate that miR-1236-3p regulates ovarian
      cancer metastasis by directly targeting ZEB1, and it may play an important role
      in the diagnosis and treatment of ovarian cancer.

PMID- 24573237
TI  - Repair of articular cartilage defects in the knee with autologous iliac crest
      cartilage in a rabbit model.
AB  - PURPOSE: To demonstrate that iliac crest cartilage may be used to repair
      articular cartilage defects in the knees of rabbits. METHODS: Full-thickness
      cartilage defects were created in the medial femoral condyle on both knees of 36
      New Zealand white rabbits. The 72 defects were randomly assigned to be repaired
      with ipsilateral iliac crest cartilage (Group I), osteochondral tissues removed
      at defect creation (Group II), or no treatment (negative control, Group III).
      Animals were killed at 6, 12, and 24 weeks post-operatively. The repaired tissues
      were harvested for magnetic resonance imaging (MRI), histological studies
      (haematoxylin and eosin and immunohistochemical staining), and mechanical
      testing. RESULTS: At 6 weeks, the iliac crest cartilage graft was not yet well
      integrated with the surrounding articular cartilage, but at 12 weeks, the graft
      deep zone had partial ossification. By 24 weeks, the hyaline cartilage-like
      tissue was completely integrated with the surrounding articular cartilage.
      Osteochondral autografts showed more rapid healing than Group I at 6 weeks and
      complete healing at 12 weeks. Untreated defects were concave or partly filled
      with fibrous tissue throughout the study. MRI showed that Group I had slower
      integration with surrounding normal cartilage compared with Group II. The
      mechanical properties of Group I were significantly lower than those of Group II
      at 12 weeks, but this difference was not significant at 24 weeks. CONCLUSION:
      Iliac crest cartilage autografts were able to repair knee cartilage defects with
      hyaline cartilage and showed comparable results with osteochondral autografts in
      the rabbit model.

PMID- 24573238
TI  - The longitudinal anatomy of the long head of the biceps tendon and implications
      on tenodesis.
AB  - PURPOSE: Regarding biceps tenodesis, there are no evidence-based recommendations
      for the ideal level at which to cut and stabilize the tendon. The purpose of this
      study is to provide information referencing the tendon for potential clinical
      applications during biceps tenodesis. METHODS: Forty-three embalmed shoulder
      specimens were dissected, and markers were placed at four points along each
      biceps tendon: (1) proximal border of the bicipital groove, (2) distal border of
      the bicipital groove, (3) proximal edge of the pectoralis major insertion, and
      (4) musculotendonous junction. Using the origin as the initial point of
      reference, measurements were made to the four subsequent sites. The humeral
      length was recorded by measuring the distance between the greater tuberosity and
      the lateral epicondyle. RESULTS: Measurements were recorded from the origin of
      the tendon on the supraglenoid tubercle to each established point along its
      length, and the mean, minimum, and maximum values (cm) were calculated as
      follows: origin to the proximal bicipital groove [2.8 (1.9, 4.3)], distal
      bicipital groove [5.2 (3.8, 7.0)], pectoralis major insertion [8.1 (6.3, 10.4)],
      and musculotendonous junction [13.8 (7.7, 20.3)], and overall humeral length
      [29.2 (25.2, 32.7)]. An analysis demonstrated a statistically significant overall
      increase in tendon length at each anatomic site as the overall humeral length
      increased (p < 0.05). Utilizing the constant and coefficient data from our
      regression analysis, a predictive formula was calculated based on humeral length.
      For example, distance from the origin to each anatomic point was determined by a
      formula [Tendon length at each anatomic landmark, cm = coefficient (humeral
      length, cm) + constant] for each respective anatomic landmark along the course of
      the tendon. CONCLUSION: This work will allow surgeons who prefer tenodesis to
      more accurately re-approximate the appropriate length-tension relationship of the
      biceps when tenodesing the tendon in a variety of locations. This benefit will
      potentially result in the most efficient biceps muscle-tendon function and
      improve the results of biceps surgery. LEVEL OF EVIDENCE: IV.

PMID- 24573239
TI  - Association between increased availability of emergency contraceptive pills and
      the sexual and contraceptive behaviors of women.
AB  - In the United States (US), access to emergency contraceptive pills (ECPs)
      expanded to nationwide in 2006 when regulators allowed Plan B, a brand of
      emergency contraception, to be sold without prescription. Using data from the
      National Health and Nutrition Examination Survey from 2001 to 2010, I examined
      any association between increased access to these ECPs in the US and negative
      consequences. I found an association between increased access to ECPs and a 2.2
      per cent higher probability of any sexual activity, a 5.2 per cent increase in
      the likelihood of reporting sex with multiple partners, an increase in the
      average number of partners by 0.35, and a -7.6 per cent decrease in the
      likelihood of injectable contraceptive use. These results suggest that policies
      in the US and other countries that expand access to ECPs should be paired with
      information on ECPs' lack of protection against sexually transmitted infections
      and relatively lower efficacy compared to other forms of contraception. 

PMID- 24573245
TI  - A remarkable activity of human leukotriene A4 hydrolase (LTA4H) toward unnatural
      amino acids.
AB  - Leukotriene A4 hydrolase (LTA4H--EC 3.3.2.6) is a bifunctional zinc
      metalloenzyme, which processes LTA4 through an epoxide hydrolase activity and is
      also able to trim one amino acid at a time from N-terminal peptidic substrates
      via its aminopeptidase activity. In this report, we have utilized a library of
      130 individual proteinogenic and unnatural amino acid fluorogenic substrates to
      determine the aminopeptidase specificity of this enzyme. We have found that the
      best proteinogenic amino acid recognized by LTA4H is arginine. However, we have
      also observed several unnatural amino acids, which were significantly better in
      terms of cleavage rate (k cat/K m values). Among them, the benzyl ester of
      aspartic acid exhibited a k cat/K m value that was more than two orders of
      magnitude higher (1.75 * 10(5) M(-1) s(-1)) as compared to L-Arg (1.5 * 10(3) M(
      1) s(-1)). This information can be used for design of potent inhibitors of this
      enzyme, but may also suggest yet undiscovered functions or specificities of
      LTA4H.

PMID- 24573240
TI  - Commentary: the global tobacco litigation initiative: an effort to protect
      developing countries from big tobacco.
AB  - The tobacco industry faces challenges in the affluent world, but preys upon poor
      and populous countries, taking advantage of underdeveloped tobacco policies. One
      of the ways to address tobacco control globally is to create a tobacco litigation
      partnership between developed and developing countries. A global litigation
      partnership has the potential to alleviate concerns over weak tobacco control
      structures in developing countries and benefit developed countries in monetary as
      well as legislative ways. 

PMID- 24573247
TI  - Heterogeneity of Li-Fraumeni syndrome links to unequal gain-of-function effects
      of p53 mutations.
AB  - Mutations of p53 cause not only loss of wild-type function but also gain of novel
      oncogenic functions (GOF). Accumulating evidence suggest that p53 hotspot
      mutations may confer different types and magnitudes of GOF. Here we add support
      to the heterogeneity of mutant p53 GOF by showing their unequal association with
      early tumor onset and spectrum of tumor types. We stratified Li-Fraumeni syndrome
      (LFS) patients according to carried p53 mutations using data from the updated p53
      germline mutation database. When compared to loss-of-function nonsense mutations,
      the R282 GOF mutation associated with significantly earlier onset, while the G245
      mutation displayed later onset. The R175, Y220, R248, R282 and nonsense mutations
      showed preferential distribution in certain cancer types, which varied in the age
      of onset. Multivariate COX regression model adjusting for cancer types and
      patient sex suggested that nonsense and G245 mutations had lower risk than R248
      for early onset, suggesting unequal strengths of mutant GOF effects. Our results
      suggest that Li-Fraumeni syndrome can be subdivided into subtypes linking to
      unequal GOF effects of p53 mutations. These findings have potential implications
      in the prevention, early detection and targeted treatment of LFS tumors. 

PMID- 24573248
TI  - The various states of von Willebrand factor and their function in physiology and
      pathophysiology.
AB  - The specific interactions of von Willebrand factor (VWF) with the vessel wall,
      platelets or other interfaces strongly depend on (a shear-induced) VWF
      activation. Shear flow has been shown to induce a conformational transition of
      VWF, but is modulated by its thermodynamic state (state-function relationship).
      The state in turn is determined by physical (e.g. vessel geometry), physico
      chemical (e.g. pH) and molecular-biological (e.g. mutants, binding) factors.
      Combining established results with recent insights, we reconstruct VWF biology
      and its state-function relationship from endothelial cell release to final
      degradation in the human vasculature. After VWF secretion, endothelial-anchored
      and shear activated VWF multimers can rapidly interact with surrounding colloids,
      typically with platelets. Simultaneously, this VWF activation enables ADAMTS13 to
      cleave VWF multimers thereby limiting VWF binding capacity. The subsequent cell
      surface dissociation leads to a VWF recoiling to a globular conformation,
      shielding from further degradation by ADAMTS13. High local concentrations of
      these soluble VWF multimers, transported to the downstream vasculature, are
      capable for an immediate reactivation and re-polymerisation initiating colloid
      binding or VWF-colloid aggregation at the site of inflamed endothelium, vessel
      injuries or pathological high-shear areas. Focusing on these functional steps in
      the lifecycle of VWF, its qualitative and quantitative deficiencies in the
      different VWD types will facilitate more precise diagnostics and reliable risk
      stratification for prophylactic therapies. The underlying biophysical principles
      are of general character, which broadens prospective studies on the physiological
      and pathophysiological impact of VWF and VWF-associated diseases and beares hope
      for a more universal understanding of an entire class of phenomena. 

PMID- 24573249
TI  - Galectin-9 induced myeloid suppressor cells expand regulatory T cells in an IL-10
      dependent manner in CVB3-induced acute myocarditis.
AB  - The objective of the study was to explore the effects of galectin-9 on myeloid
      suppressor cells in Coxsackievirus B3 (CVB3)-induced myocarditis and the possible
      mechanisms involved. For this purpose, BALB/c male mice were infected with CVB3
      on day 0 and then received intraperitoneal (IP) administration of recombinant
      galectin-9 or phosphate-buffered saline (PBS) daily from day 3 to day 7. The
      phenotypes and functions of myeloid suppressor cells were evaluated. The role and
      mechanism of myeloid suppressor cells and subsets in CVB3-induced myocarditis in
      vitro were explored. We found that galectin-9 remarkably increased the
      frequencies of CD11b+Gr-1+ cells in the cardiac tissue and spleen with
      myocarditis. Ly-6G+ cells were decreased and Ly-6C+ cells were increased in
      galectin-9-treated mice. In addition, CD11b+Gr-1+ cells were highly effective in
      suppressing CD4+ T cells. Moreover, our data demonstrate that CD11b+Gr-1+ cells
      are capable of expanding regulatory T cells (Tregs) from a preexisting population
      of natural Tregs, which depends on IL-10 but not TGF-beta. Our results indicate
      that galectin-9 therapy may represent a useful approach to ameliorate CVB3
      induced myocarditis. 

PMID- 24573250
TI  - Development of lipid-shell and polymer core nanoparticles with water-soluble
      salidroside for anti-cancer therapy.
AB  - Salidroside (Sal) is a potent antitumor drug with high water-solubility. The
      clinic application of Sal in cancer therapy has been significantly restricted by
      poor oral absorption and low tumor cell uptake. To solve this problem, lipid
      shell and polymer-core nanoparticles (Sal-LPNPs) loaded with Sal were developed
      by a double emulsification method. The processing parameters including the
      polymer types, organic phase, PVA types and amount were systemically
      investigated. The obtained optimal Sal-LPNPs, composed of PLGA-PEG-PLGA triblock
      copolymers and lipids, had high entrapment efficiency (65%), submicron size (150
      nm) and negatively charged surface (-23 mV). DSC analysis demonstrated the
      successful encapsulation of Sal into LPNPs. The core-shell structure of Sal-LPNPs
      was verified by TEM. Sal released slowly from the LPNPs without apparent burst
      release. MTT assay revealed that 4T1 and PANC-1 cancer cell lines were sensitive
      to Sal treatment. Sal-LPNPs had significantly higher antitumor activities than
      free Sal in 4T1 and PANC-1 cells. The data indicate that LPNPs are a promising
      Sal vehicle for anti-cancer therapy and worthy of further investigation. 

PMID- 24573251
TI  - Improved establishment of embryonic stem (ES) cell lines from the Chinese Kunming
      mice by hybridization with 129 mice.
AB  - Chinese Kunming mice (Mus musculus Km), widely used as laboratory animals
      throughout China, remain very refractory for embryonic stem (ES) cell isolation.
      The present study was aimed to evaluate the effects of hybridization with 129/Sv
      mice, and culture media containing fetal bovine serum (FBS) or Knockout serum
      replacement (KSR) on ES cell isolation from Kunming mice. The results
      demonstrated that ES cells had been effectively isolated from the hybrid embryos
      of Kunming and 129/Sv mice using all three media containing 15% FBS, 15% KSR and
      their mixture of 14% KSR and 1% FBS, individually. These isolated ES cells had
      maintained in vitro undifferentiated for a long time, exhibiting all features
      specific for mouse ES cells. In addition, the rates of ES cell isolation in the
      medium containing 14% KSR and 1% FBS, was 46.67% and significantly higher than
      those in another two media containing only FBS or KSR (p < 0.05). Contrarily, no
      ES cell line had been established from Kunming mouse inbred embryos using the
      same protocols. These results suggested that ES cells with long-term self-renewal
      ability could be efficiently generated from hybrid embryos of Kunming and 129/Sv
      mice, and a small volume of FBS was necessary to isolate ES cells in the KSR
      medium when embryos and early ES cells cultured. 

PMID- 24573255
TI  - Ergotism in Norway. Part 2: The symptoms and their interpretation from the
      eighteenth century onwards.
AB  - Ergotism, the disease caused by consuming Claviceps purpurea, a highly poisonous,
      grain-infecting fungus, occurred at various places scattered throughout Norway
      during the eighteenth and nineteenth centuries. By focusing on these cases we
      chart the changing interpretations of the peculiar disease, frequently understood
      within a religious context or considered as a supernatural (e.g. ghostly)
      experience. However, there was a growing awareness of the disease ergotism, and
      from the late eighteenth century onwards it was often correctly interpreted as
      being due to a fungus consumed via bread or porridge. Also, nineteenth-century
      fairy-tales and regional legends reveal that people were increasingly aware and
      fearful of the effects of consuming infected grain. 

PMID- 24573256
TI  - From psychiatric symptom to diagnostic category: self-harm from the Victorians to
      DSM-5.
AB  - It is rare that a symptom becomes a disease entity. 'Self-harm' is now a full
      fledged diagnostic category for DSM-5. The existing literature of the topic
      posits that it is a trans-historical psychiatric category and that examples of
      self-harm can be found from the earliest written records, which is part of the
      underlying argument for its inclusion in DSM-5. But how old is self-harm and
      indeed what defines 'self-harm' historically and culturally? 

PMID- 24573257
TI  - Neopositivism and the DSM psychiatric classification. An epistemological history.
      Part 1: Theoretical comparison.
AB  - Recent research suggests that the DSM psychiatric classification is in a
      paradigmatic crisis and that the DSM-5 will be unable to overcome it. One
      possible reason is that the DSM is based on a neopositivist epistemology which is
      inadequate for the present-day needs of psychopathology. However, in which sense
      is the DSM a neopositivist system? This paper will explore the theoretical
      similarities between the DSM structure and the neopositivist basic assumptions.
      It is shown that the DSM has the following neopositivist features: (a) a sharp
      distinction between scientific and non-scientific diagnoses; (b) the exclusion of
      the latter as nonsensical; (c) the faith on the existence of a purely observable
      basis (the description of reliable symptoms); (d) the introduction of the
      operative diagnostic criteria as rules of correspondence linking the
      observational level to the diagnostic concept. 

PMID- 24573253
TI  - Genistein-inhibited cancer stem cell-like properties and reduced chemoresistance
      of gastric cancer.
AB  - Genistein, the predominant isoflavone found in soy products, has exerted its
      anticarcinogenic effect in many different tumor types in vitro and in vivo.
      Accumulating evidence in recent years has strongly indicated the existence of
      cancer stem cells in gastric cancer. Here, we showed that low doses of genistein
      (15 uM), extracted from Millettia nitida Benth var hirsutissima Z Wei, inhibit
      tumor cell self-renewal in two types of gastric cancer cells by colony formation
      assay and tumor sphere formation assay. Treatment of gastric cancer cells with
      genistein reduced its chemoresistance to 5-Fu (fluorouracil) and ciplatin.
      Further results indicated that the reduced chemoresistance may be associated with
      the inhibition of ABCG2 expression and ERK 1/2 activity. Furthermore, genistein
      reduced tumor mass in the xenograft model. Together, genistein inhibited gastric
      cancer stem cell-like properties and reduced its chemoresistance. Our results
      provide a further rationale and experimental basis for using the genistein to
      improve treatment of patients with gastric cancer.

PMID- 24573258
TI  - A 'German world' shared among doctors: a history of the relationship between
      Japanese and German psychiatry before World War II.
AB  - This article deals with the critical history of German and Japanese psychiatrists
      who dreamed of a 'German world' that would cross borders. It analyses their
      discourse, not only by looking at their biographical backgrounds, but also by
      examining them in a wider context linked to German academic predominance and
      cultural propaganda before World War II. By focusing on Wilhelm Stieda, Wilhelm
      Weygandt and Kure Shuzo, the article shows that the positive evaluation of
      Japanese psychiatry by the two Germans encouraged Kure, who was eager to
      modernize the treatment of and institutions for the mentally ill in Japan. Their
      statements on Japanese psychiatry reflect their ideological and historical
      framework, with reference to national/ethnic identity, academic position, and the
      relationship between Germany and Japan. 

PMID- 24573259
TI  - The bones of the insane.
AB  - This article examines alienist explanations for fracture among British asylum
      patients in the late nineteenth to early twentieth centuries. A series of deaths
      in asylums came to light in the 1870s which, in placing the blame for such
      incidents on asylum staff, called for a response from the psychiatric profession.
      This response drew upon other medical fields and employed novel pathological
      techniques to explain why fractures occurred among the insane, in many cases
      aligning bone fragility with particular forms of insanity (namely, General
      Paralysis of the Insane). Although such research aimed to provide a medical
      explanation for the 'fracture death', it also called into question the value of
      pathological research and the utility of quantitative measurement in
      understanding mental disease. 

PMID- 24573260
TI  - The theoretical root of Karl Jaspers' General Psychopathology. Part 1:
      Reconsidering the influence of phenomenology and hermeneutics.
AB  - The present paper investigates the methodology involved in Jaspers'
      psychopathology and compares it with Husserl's phenomenology and with Dilthey's
      cultural science. Allgemeine Psychopathologie and other methodological works by
      Jaspers, the works of Husserl and Dilthey that Jaspers cited, and previous
      research papers on Jaspers are reviewed. Jaspers had conflicting views on
      understanding, which were comprised of both empathic understanding and rational,
      ideal-typical understanding. Such a standpoint on understanding is considerably
      different from Dilthey's. Additionally, the present paper reconfirms that
      Jaspers' 'phenomenology' as a form of descriptive psychology for the
      understanding of empirical psychic states is different from Husserl's
      phenomenology. Thus, this paper casts doubt on the common opinion that Jaspers
      was under the profound influence of Husserl or Dilthey. 

PMID- 24573252
TI  - Genotoxic anti-cancer agents and their relationship to DNA damage, mitosis, and
      checkpoint adaptation in proliferating cancer cells.
AB  - When a human cell detects damaged DNA, it initiates the DNA damage response (DDR)
      that permits it to repair the damage and avoid transmitting it to daughter cells.
      Despite this response, changes to the genome occur and some cells, such as
      proliferating cancer cells, are prone to genome instability. The cellular
      processes that lead to genomic changes after a genotoxic event are not well
      understood. Our research focuses on the relationship between genotoxic cancer
      drugs and checkpoint adaptation, which is the process of mitosis with damaged
      DNA. We examine the types of DNA damage induced by widely used cancer drugs and
      describe their effects upon proliferating cancer cells. There is evidence that
      cell death caused by genotoxic cancer drugs in some cases includes exiting a DNA
      damage cell cycle arrest and entry into mitosis. Furthermore, some cells are able
      to survive this process at a time when the genome is most susceptible to change
      or rearrangement. Checkpoint adaptation is poorly characterised in human cells;
      we predict that increasing our understanding of this pathway may help to
      understand genomic instability in cancer cells and provide insight into methods
      to improve the efficacy of current cancer therapies. 

PMID- 24573261
TI  - 'Struensee's memoir on the situation of the King' (1772): Christian VII of
      Denmark.
AB  - Christian VII of Denmark (1749-1808) was insane throughout his long reign. The
      royal physician, Johann Friedrich Struensee (1737-72), usurped his power. In 1771
      the King appointed him Privy Cabinet Minister. Struensee revolutionized the whole
      administration of the Danish-Norwegian kingdom and had an adulterous relationship
      with the Queen, Caroline Mathilda, George III's sister. In January 1772 he was
      arrested, sentenced to death for lese-majesty and executed. During his
      confinement, he wrote a memoir on the King's condition, which he considered to be
      caused by, or the effect of, masturbation. In 1906 Christiansen interpreted it as
      a case of dementia praecox, i.e. schizophrenia. It is now suggested that
      Christian's insanity, like that of George III (his cousin), might have been due
      to porphyria - the 'royal malady', possibly inherited through his mother,
      Princess Louise of England or his father, King Frederik V, who died from an
      illness which retrospectively resembles a case of porphyria. 

PMID- 24573271
TI  - A motor-oriented organization of human ventral visual cortex?

PMID- 24573272
TI  - Comparison of five peptide vectors for improved brain delivery of the lysosomal
      enzyme arylsulfatase A.
AB  - Enzyme replacement therapy (ERT) is a treatment option for lysosomal storage
      disorders (LSDs) caused by deficiencies of soluble lysosomal enzymes. ERT depends
      on receptor-mediated transport of intravenously injected recombinant enzyme to
      lysosomes of patient cells. The blood-brain barrier (BBB) prevents efficient
      transfer of therapeutic polypeptides from the blood to the brain parenchyma and
      thus hinders effective treatment of LSDs with CNS involvement. We compared the
      potential of five brain-targeting peptides to promote brain delivery of the
      lysosomal enzyme arylsulfatase A (ASA). Fusion proteins between ASA and the
      protein transduction domain of the human immunodeficiency virus TAT protein
      (Tat), an Angiopep peptide (Ang-2), and the receptor-binding domains of human
      apolipoprotein B (ApoB) and ApoE (two versions, ApoE-I and ApoE-II) were
      generated. All ASA fusion proteins were enzymatically active and targeted to
      lysosomes when added to cultured cells. In contrast to wild-type ASA, which is
      taken up by mannose-6-phosphate receptors, all chimeric proteins were
      additionally endocytosed via mannose-6-phosphate-independent routes. For ASA-Ang
      2, ASA-ApoE-I, and ASA-ApoE-II, uptake was partially due to the low-density
      lipoprotein receptor-related protein 1. Transendothelial transfer in a BBB cell
      culture model was elevated for ASA-ApoB, ASA-ApoE-I, and ASA-ApoE-II. Brain
      delivery was, however, increased only for ASA-ApoE-II. ApoE-II was also superior
      to wild-type ASA in reducing lysosomal storage in the CNS of ASA-knock-out mice
      treated by ERT. Therefore, the ApoE-derived peptide appears useful to treat
      metachromatic leukodystrophy and possibly other neurological disorders more
      efficiently. 

PMID- 24573273
TI  - ASIC1a activation enhances inhibition in the basolateral amygdala and reduces
      anxiety.
AB  - The discovery that even small changes in extracellular acidity can alter the
      excitability of neuronal networks via activation of acid-sensing ion channels
      (ASICs) could have therapeutic application in a host of neurological and
      psychiatric illnesses. Recent evidence suggests that activation of ASIC1a, a
      subtype of ASICs that is widely distributed in the brain, is necessary for the
      expression of fear and anxiety. Antagonists of ASIC1a, therefore, have been
      proposed as a potential treatment for anxiety. The basolateral amygdala (BLA) is
      central to fear generation, and anxiety disorders are characterized by BLA
      hyperexcitability. To better understand the role of ASIC1a in anxiety, we
      attempted to provide a direct assessment of whether ASIC1a activation increases
      BLA excitability. In rat BLA slices, activation of ASIC1a by low pH or ammonium
      elicited inward currents in both interneurons and principal neurons, and
      increased spontaneous IPSCs recorded from principal cells significantly more than
      spontaneous EPSCs. Epileptiform activity induced by high potassium and low
      magnesium was suppressed by ammonium. Antagonism of ASIC1a decreased spontaneous
      IPSCs more than EPSCs, and increased the excitability of the BLA network, as
      reflected by the pronounced increase of evoked field potentials, suggesting that
      ASIC1a channels are active in the basal state. In vivo activation or blockade of
      ASIC1a in the BLA suppressed or increased, respectively, anxiety-like behavior.
      Thus, in the rat BLA, ASIC1a has an inhibitory and anxiolytic function. The
      discovery of positive ASIC1a modulators may hold promise for the treatment of
      anxiety disorders. 

PMID- 24573274
TI  - Neuropeptidergic signaling partitions arousal behaviors in zebrafish.
AB  - Animals modulate their arousal state to ensure that their sensory responsiveness
      and locomotor activity match environmental demands. Neuropeptides can regulate
      arousal, but studies of their roles in vertebrates have been constrained by the
      vast array of neuropeptides and their pleiotropic effects. To overcome these
      limitations, we systematically dissected the neuropeptidergic modulation of
      arousal in larval zebrafish. We quantified spontaneous locomotor activity and
      responsiveness to sensory stimuli after genetically induced expression of seven
      evolutionarily conserved neuropeptides, including adenylate cyclase activating
      polypeptide 1b (adcyap1b), cocaine-related and amphetamine-related transcript
      (cart), cholecystokinin (cck), calcitonin gene-related peptide (cgrp), galanin,
      hypocretin, and nociceptin. Our study reveals that arousal behaviors are
      dissociable: neuropeptide expression uncoupled spontaneous activity from sensory
      responsiveness, and uncovered modality-specific effects upon sensory
      responsiveness. Principal components analysis and phenotypic clustering revealed
      both shared and divergent features of neuropeptidergic functions: hypocretin and
      cgrp stimulated spontaneous locomotor activity, whereas galanin and nociceptin
      attenuated these behaviors. In contrast, cart and adcyap1b enhanced sensory
      responsiveness yet had minimal impacts on spontaneous activity, and cck
      expression induced the opposite effects. Furthermore, hypocretin and nociceptin
      induced modality-specific differences in responsiveness to changes in
      illumination. Our study provides the first systematic and high-throughput
      analysis of neuropeptidergic modulation of arousal, demonstrates that arousal can
      be partitioned into independent behavioral components, and reveals novel and
      conserved functions of neuropeptides in regulating arousal. 

PMID- 24573275
TI  - Absence of transient receptor potential vanilloid-1 accelerates stress-induced
      axonopathy in the optic projection.
AB  - How neurons respond to stress in degenerative disease is of fundamental
      importance for identifying mechanisms of progression and new therapeutic targets.
      Members of the transient receptor potential (TRP) family of cation-selective ion
      channels are candidates for mediating stress signals, since different subunits
      transduce a variety of stimuli relevant in both normal and pathogenic physiology.
      We addressed this possibility for the TRP vanilloid-1 (TRPV1) subunit by
      comparing how the optic projection of Trpv1(-/-) mice and age-matched C57
      controls responds to stress from elevated ocular pressure, the critical stressor
      in the most common optic neuropathy, glaucoma. Over a 5 week period of elevated
      pressure induced by microbead occlusion of ocular fluid, Trpv1(-/-) accelerated
      both degradation of axonal transport from retinal ganglion cells to the superior
      colliculus and degeneration of the axons themselves in the optic nerve. Ganglion
      cell body loss, which is normally later in progression, occurred in nasal sectors
      of Trpv1(-/-) but not C57 retina. Pharmacological antagonism of TRPV1 in rats
      similarly accelerated ganglion cell axonopathy. Elevated ocular pressure resulted
      in differences in spontaneous firing rate and action potential threshold current
      in Trpv1(-/-) ganglion cells compared with C57. In the absence of elevated
      pressure, ganglion cells in the two strains had similar firing patterns. Based on
      these data, we propose that TRPV1 may help neurons respond to disease-relevant
      stressors by enhancing activity necessary for axonal signaling. 

PMID- 24573276
TI  - Proteasome modulates positive and negative translational regulators in long-term
      synaptic plasticity.
AB  - Proteolysis by the ubiquitin-proteasome pathway appears to have a complex role in
      synaptic plasticity, but its various functions remain to be elucidated. Using
      late phase long-term potentiation (L-LTP) in the hippocampus of the mouse as a
      model for long-term synaptic plasticity, we previously showed that inhibition of
      the proteasome enhances induction but blocks maintenance of L-LTP. In this study,
      we investigated the possible mechanisms by which proteasome inhibition has
      opposite effects on L-LTP induction and maintenance. Our results show that
      inhibiting phosphatidyl inositol-3 kinase or blocking the interaction between
      eukaryotic initiation factors 4E (eIF4E) and 4G (eIF4G) reduces the enhancement
      of L-LTP induction brought about by proteasome inhibition suggesting interplay
      between proteolysis and the signaling pathway mediated by mammalian target of
      rapamycin (mTOR). Also, proteasome inhibition leads to accumulation of
      translational activators in the mTOR pathway such as eIF4E and eukaryotic
      elongation factor 1A (eEF1A) early during L-LTP causing increased induction.
      Furthermore, inhibition of the proteasome causes a buildup of translational
      repressors, such as polyadenylate-binding protein interacting protein 2 (Paip2)
      and eukaryotic initiation factor 4E-binding protein 2 (4E-BP2), during late
      stages of L-LTP contributing to the blockade of L-LTP maintenance. Thus, the
      proteasome plays a critical role in regulating protein synthesis during L-LTP by
      tightly controlling translation. Our results provide novel mechanistic insights
      into the interplay between protein degradation and protein synthesis in long-term
      synaptic plasticity. 

PMID- 24573277
TI  - Glutamate and dopamine transmission from midbrain dopamine neurons share similar
      release properties but are differentially affected by cocaine.
AB  - Synaptic transmission between ventral tegmental area and nucleus accumbens (NAc)
      is critically involved in reward-motivated behaviors and thought to be altered in
      addiction. In addition to dopamine (DA), glutamate is packaged and released by a
      subset of mesolimbic DA neurons, eliciting EPSCs onto medium spiny neurons in
      NAc. Little is known about the properties and modulation of glutamate release
      from DA midbrain terminals and the effect of cocaine. Using an optogenetic
      approach to selectively activate midbrain DA fibers, we compared the properties
      and modulation of DA transients and EPSCs measured using fast-scan cyclic
      voltammetry and whole-cell recordings in mouse brain slices. DA transients and
      EPSCs were inhibited by DA receptor D2R agonist and showed a marked paired-pulse
      depression that required 2 min for full recovery. Cocaine depressed EPSCs
      amplitude by 50% but enhanced the overall DA transmission from midbrain DA
      neurons. AMPA and NMDA receptor-mediated EPSCs were equally inhibited by cocaine,
      suggesting a presynaptic mechanism of action. Pharmacological blockage and
      genetic deletion of D2R in DA neurons prevented the cocaine-induced inhibition of
      EPSCs and caused a larger increase in DA transient peak, confirming the
      involvement of presynaptic D2R. These findings demonstrate that acute cocaine
      inhibits DA and glutamate release from midbrain DA neurons via presynaptic D2R
      but has differential overall effects on their transmissions in the NAc. We
      postulate that cocaine, by blocking DA reuptake, prolongs DA transients and
      facilitates the feedback inhibition of DA and glutamate release from these
      terminals. 

PMID- 24573278
TI  - alpha1F64 Residue at GABA(A) receptor binding site is involved in gating by
      influencing the receptor flipping transitions.
AB  - GABA receptors (GABAARs) mediate inhibition in the adult brain. These channels
      are heteropentamers and their ligand binding sites are localized at the beta+ /
      alpha- interfaces. As expected, mutations of binding-site residues affect binding
      kinetics but accumulating evidence indicates that gating is also altered,
      although the underlying mechanisms are unclear. We investigated the impact of the
      hydrophobic box residue localized at alpha1(-), F64 (alpha1F64), on the binding
      and gating of rat recombinant alpha1beta1gamma2 receptors. The analysis of
      current responses to rapid agonist applications confirmed a marked effect of
      alpha1F64 mutations on agonist binding and revealed surprisingly strong effects
      on gating, including the disappearance of rapid desensitization, the slowing of
      current onset, and accelerated deactivation. Moreover, nonstationary variance
      analysis revealed that the alpha1F64C mutation dramatically reduced the maximum
      open probability without altering channel conductance. Interestingly, for wild
      type receptors, responses to saturating concentration of a partial agonist, P4S,
      showed no rapid desensitization, similar to GABA-evoked responses mediated by
      alpha1F64C mutants. For the alpha1F64L mutation, the application of the high
      affinity agonist muscimol partially rescued rapid desensitization compared with
      responses evoked by GABA. These findings suggest that alpha1F64 mutations do not
      disrupt desensitization mechanisms but rather affect other gating features that
      obscure it. Model simulations indicated that all of our observations related to
      alpha1F64 mutations could be properly reproduced by altering the flipped state
      transitions that occurred after agonist binding but preceded opening. In
      conclusion, we propose that the alpha1F64 residue may participate in linking
      binding and gating by influencing flipping kinetics.

PMID- 24573279
TI  - Motivational tuning of fronto-subthalamic connectivity facilitates control of
      action impulses.
AB  - It is critical for survival to quickly respond to environmental stimuli with the
      most appropriate action. This task becomes most challenging when response
      tendencies induced by relevant and irrelevant stimulus features are in conflict,
      and have to be resolved in real time. Inputs from the pre-supplementary motor
      area (pre-SMA) and inferior frontal gyrus (IFG) to the subthalamic nucleus (STN)
      are thought to support this function, but the connectivity and causality of these
      regions in calibrating motor control has not been delineated. In this study, we
      combined off-line noninvasive brain stimulation and functional magnetic resonance
      imaging, while young healthy human participants performed a modified version of
      the Simon task. We show that impairing pre-SMA function by noninvasive brain
      stimulation improved control over impulsive response tendencies, but only when
      participants were explicitly rewarded for fast and accurate responses. These
      effects were mediated by enhanced activation and connectivity of the IFG-STN
      pathway. These results provide causal evidence for a pivotal role of the IFG-STN
      pathway during action control. Additionally, they suggest a parallel rather than
      hierarchical organization of the pre-SMA-STN and IFG-STN pathways, since
      interruption of pre-SMA function can enhance IFG-STN connectivity and improve
      control over inappropriate responses. 

PMID- 24573282
TI  - Large somatic synapses on neurons in the ventral lateral lemniscus work in pairs.
AB  - In the auditory system, large somatic synapses convey strong excitation that
      supports temporally precise information transfer. The information transfer of
      such synapses has predominantly been investigated in the endbulbs of Held in the
      anterior ventral cochlear nucleus and the calyx of Held in the medial nucleus of
      the trapezoid body. These large synapses either work as relays or integrate over
      a small number of inputs to excite the postsynaptic neuron beyond action
      potential (AP) threshold. In the monaural system, another large somatic synapse
      targets neurons in the ventral nucleus of the lateral lemniscus (VNLL). Here, we
      comparatively analyze the mechanisms of synaptic information transfer in endbulbs
      in the VNLL and the calyx of Held in juvenile Mongolian gerbils. We find that
      endbulbs in the VNLL are functionally surface-scaled versions of the calyx of
      Held with respect to vesicle availability, release efficacy, and synaptic peak
      currents. This functional scaling is achieved by different calcium current
      kinetics that compensate for the smaller AP in VNLL endbulbs. However, the
      average postsynaptic current in the VNLL fails to elicit APs in its target
      neurons, even though equal current suffices to generate APs in neurons
      postsynaptic to the calyx of Held. In the VNLL, a postsynaptic A-type outward
      current reduces excitability and prevents AP generation upon a single presynaptic
      input. Instead, coincidence detection of inputs from two converging endbulbs is
      ideal to reliably trigger APs. Thus, even large endbulbs do not guarantee one-to
      one AP transfer. Instead, information flow appears regulated by circuit
      requirements. 

PMID- 24573281
TI  - The shape of dendritic arbors in different functional domains of the cortical
      orientation map.
AB  - The neocortex is organized into macroscopic functional maps. However, at the
      microscopic scale, the functional preference and degree of feature selectivity
      between neighboring neurons can vary considerably. In the primary visual cortex,
      adjacent neurons in iso-orientation domains share the same orientation
      preference, whereas neighboring neurons near pinwheel centers are tuned to
      different stimulus orientations. Moreover, several studies have found greater
      orientation selectivity in iso-orientation domains than in pinwheel centers.
      These differences suggest that neurons sample local inputs in a spatially
      homogenous fashion and independently of the location of their soma on the
      orientation map. Here we determine whether dendritic geometry is affected by
      neuronal position on the orientation map. We labeled individual layer 2/3
      pyramidal neurons with fluorescent dyes in specific domains of the orientation
      map in cat primary visual cortex and imaged their dendritic trees in vivo by two
      photon microscopy. We found that the circularity and uniformity of dendritic
      trees is independent of somatic position on the orientation map. Moreover, the
      dendrites of neurons located close to pinwheel centers extend across all
      orientation domains in an unbiased fashion. Thus, unbiased dendritic trees appear
      to provide an anatomical substrate for the systematic variations in feature
      selectivity across the orientation map. 

PMID- 24573283
TI  - Figure-ground processing during fixational saccades in V1: indication for higher
      order stability.
AB  - In a typical visual scene we continuously perceive a "figure" that is segregated
      from the surrounding "background" despite ongoing microsaccades and small
      saccades that are performed when attempting fixation (fixational saccades [FSs]).
      Previously reported neuronal correlates of figure-ground (FG) segregation in the
      primary visual cortex (V1) showed enhanced activity in the "figure" along with
      suppressed activity in the noisy "background." However, it is unknown how this FG
      modulation in V1 is affected by FSs. To investigate this question, we trained two
      monkeys to detect a contour embedded in a noisy background while simultaneously
      imaging V1 using voltage-sensitive dyes. During stimulus presentation, the
      monkeys typically performed 1-3 FSs, which displaced the contour over the retina.
      Using eye position and a 2D analytical model to map the stimulus onto V1, we were
      able to compute FG modulation before and after each FS. On the spatial cortical
      scale, we found that, after each FS, FG modulation follows the stimulus retinal
      displacement and "hops" within the V1 retinotopic map, suggesting visual
      instability. On the temporal scale, FG modulation is initiated in the new
      retinotopic position before it disappeared from the old retinotopic position.
      Moreover, the FG modulation developed faster after an FS, compared with after
      stimulus onset, which may contribute to visual stability of FG segregation, along
      the timeline of stimulus presentation. Therefore, despite spatial discontinuity
      of FG modulation in V1, the higher-order stability of FG modulation along time
      may enable our stable and continuous perception. 

PMID- 24573280
TI  - Nonvisual complex spike signals in the rabbit cerebellar flocculus.
AB  - In addition to the well-known signals of retinal image slip, floccular complex
      spikes (CSs) also convey nonvisual signals. We recorded eye movement and CS
      activity from Purkinje cells in awake rabbits sinusoidally oscillated in the dark
      on a vestibular turntable. The stimulus frequency ranged from 0.2 to 1.2 Hz, and
      the velocity amplitude ranged from 6.3 to 50 degrees /s. The average CS
      modulation was evaluated at each combination of stimulus frequency and amplitude.
      More than 75% of the Purkinje cells carried nonvisual CS signals. The amplitude
      of this modulation remained relatively constant over the entire stimulus range.
      The phase response of the CS modulation in the dark was opposite to that during
      the vestibulo-ocular reflex (VOR) in the light. With increased frequency, the
      phase response systematically shifted from being aligned with contraversive head
      velocity toward peak contralateral head position. At fixed frequency, the phase
      response was dependent on peak head velocity, indicating a system nonlinearity.
      The nonvisual CS modulation apparently reflects a competition between eye
      movement and vestibular signals, resulting in an eye movement error signal
      inferred from nonvisual sources. The combination of this error signal with the
      retinal slip signal in the inferior olive results in a net error signal reporting
      the discrepancy between the actual visually measured eye movement error and the
      inferred eye movement error derived from measures of the internal state. The
      presence of two error signals requires that the role of CSs in models of the
      floccular control of VOR adaption be expanded beyond retinal slip. 

PMID- 24573285
TI  - The emotional homunculus: ERP evidence for independent somatosensory responses
      during facial emotional processing.
AB  - Current models of face perception propose that initial visual processing is
      followed by activation of nonvisual somatosensory areas that contributes to
      emotion recognition. To test whether there is a pure and independent involvement
      of somatosensory cortex (SCx) during face processing over and above visual
      responses, we directly measured participants' somatosensory-evoked activity by
      tactually probing (105 ms postvisual facial stimuli) the state of SCx during an
      emotion discrimination task while controlling for visual effects. Discrimination
      of emotional versus neutral expressions enhanced early somatosensory-evoked
      activity between 40 and 80 ms after stimulus onset, suggesting visual emotion
      processing in SCx. This effect was source localized within primary, secondary,
      and associative somatosensory cortex. Emotional face processing influenced
      somatosensory responses to both face (congruent body part) and finger (control
      site) tactile stimulation, suggesting a general process that includes nonfacial
      cortical representations. Gender discrimination of the same facial expressions
      did not modulate somatosensory-evoked activity. We provide novel evidence that
      SCx activation is not a byproduct of visual processing but is independently
      shaped by face emotion processing. 

PMID- 24573284
TI  - M5 receptor activation produces opposing physiological outcomes in dopamine
      neurons depending on the receptor's location.
AB  - Of the five muscarinic receptor subtypes, the M5 receptor is the only one
      detectable in midbrain dopaminergic neurons, making it an attractive potential
      therapeutic target for treating disorders in which dopaminergic signaling is
      disrupted. However, developing an understanding of the role of M5 in regulating
      midbrain dopamine neuron function has been hampered by a lack of subtype
      selective compounds. Here, we extensively characterize the novel compound
      VU0238429 and demonstrate that it acts as a positive allosteric modulator with
      unprecedented selectivity for the M5 receptor. We then used VU0238429, along with
      M5 knock-out mice, to elucidate the role of this receptor in regulating
      substantia nigra pars compacta (SNc) neuron physiology in both mice and rats. In
      sagittal brain slices that isolate the SNc soma from their striatal terminals,
      activation of muscarinic receptors induced Ca2+ mobilization and inward currents
      in SNc dopamine neurons, both of which were potentiated by VU0238429 and absent
      in M5 knock-out mice. Activation of M5 also increased the spontaneous firing rate
      of SNc neurons, suggesting that activation of somatodendritic M5 increases the
      intrinsic excitability of SNc neurons. However, in coronal slices of the
      striatum, potentiation of M5 with VU0238429 resulted in an inhibition in dopamine
      release as monitored with fast scan cyclic voltammetry. Accordingly, activation
      of M5 can lead to opposing physiological outcomes depending on the location of
      the receptor. Although activation of somatodendritic M5 receptors on SNc neurons
      leads to increased neuronal firing, activation of M5 receptors in the striatum
      induces an inhibition in dopamine release.

PMID- 24573287
TI  - Representation of outcome risk and action in the anterior caudate nucleus.
AB  - The anterior caudate nucleus is essential for goal-directed behavior because it
      links outcome information to actions. It is well known that caudate neurons
      provide a variety of reward-related and action signals. However, it is still
      unclear how the two signals are integrated. We investigated whether and how
      outcome risk modulates spatial representation. We recorded neural activity in the
      anterior caudate nucleus while monkeys made saccades to multiple spatial targets,
      each associated with either fixed (safe) or variable (risky) amount of reward. We
      report that individual neurons combined the outcome reward signal with spatial
      information about the direction of saccades. These signals could be reliably read
      out from the populations of neurons. Moreover, the prospect of a risky outcome
      improved the quality of spatial information. These results provide direct
      evidence that global spatial representation in the caudate is modulated by
      outcome, which can be important for flexible control of behavior, particularly
      during learning and habit formation, when outcomes vary. 

PMID- 24573286
TI  - Transduction for pheromones in the main olfactory epithelium is mediated by the
      Ca2+ -activated channel TRPM5.
AB  - Growing evidence suggests that the main olfactory epithelium contains a subset of
      olfactory sensory neurons (OSNs) responding to pheromones. One candidate
      subpopulation expresses the calcium activated cation channel TRPM5 (transient
      receptor potential channel M5). Using GFP driven by the TRPM5 promoter in mice,
      we show that this subpopulation responds to putative pheromones, urine, and major
      histocompatibility complex peptides, but not to regular odors or a pheromone
      detected by other species. In addition, this subpopulation of TRPM5-GFP+ OSNs
      uses novel transduction. In regular OSNs, odorants elicit activation of the
      cyclic nucleotide-gated (CNG) channel, leading to Ca2+ gating of Cl- channels; in
      TRPM5-GFP+ OSNs, the Ca2+ -activated Cl- ANO2 (anoctamin 2) channel is not
      expressed, and pheromones elicit activation of the CNG channel leading to Ca2+
      gating of TRPM5. In conclusion, we show that OSNs expressing TRPM5 respond to
      pheromones, but not to regular odors through the opening of CNG channels leading
      to Ca2+ gating of TRPM5.

PMID- 24573289
TI  - Intracellular correlates of stimulus-specific adaptation.
AB  - Stimulus-specific adaptation (SSA) is the reduction in response to a common
      stimulus that does not generalize, or only partially generalizes, to rare
      stimuli. SSA is strong and widespread in primary auditory cortex (A1) of rats,
      but is weak or absent in the main input station to A1, the ventral division of
      the medial geniculate body. To study SSA in A1, we recorded neural activity in A1
      intracellularly using sharp electrodes. We studied the responses to tone pips of
      the same frequency in different contexts: as Standard and Deviants in Oddball
      sequences; in equiprobable sequences; in sequences consisting of rare tone
      presentations; and in sequences composed of many different frequencies, each of
      which was rare. SSA was found both in subthreshold membrane potential
      fluctuations and in spiking responses of A1 neurons. SSA for changes in frequency
      was large at a frequency difference of 44% between Standard and Deviant, and
      clearly present with tones separated by as little as 4%, near the behavioral
      frequency difference limen in rats. When using equivalent measures, SSA in
      spiking responses was generally larger than the SSA at the level of the membrane
      potential. This effect can be traced to the nonlinearity of the transformation
      between membrane potential to spikes. Using the responses to the same tone in
      different contexts made it possible to demonstrate that cortical SSA could not be
      fully explained by adaptation in narrow frequency channels, even at the level of
      the membrane potential. We conclude that local processing significantly
      contributes to the generation of cortical SSA. 

PMID- 24573288
TI  - Functional motifs composed of morphologically homologous neurons repeated in the
      hindbrain segments.
AB  - Segmental organization along the neuraxis is a prominent feature of the CNS in
      vertebrates. In a wide range of fishes, hindbrain segments contain orderly
      arranged reticulospinal neurons (RSNs). Individual RSNs in goldfish and zebrafish
      hindbrain are morphologically identified. RSNs sharing similar morphological
      features are called segmental homologs and repeated in adjacent segments.
      However, little is known about functional relationships among segmental homologs.
      Here we investigated the electrophysiological connectivity between the Mauthner
      cell (M-cell), a pair of giant RSNs in segment 4 (r4) that are known to trigger
      fast escape behavior, and different series of homologous RSNs in r4-r6. Paired
      intracellular recordings in adult goldfish revealed unidirectional connections
      from the M-cell to RSNs. The connectivity was similar in morphological homologs.
      A single M-cell spike produced IPSPs in dorsally located RSNs (MiD cells) on the
      ipsilateral side and excitatory postsynaptic depolarization on the contralateral
      side, except for MiD2cm cells. The inhibitory or excitatory potentials
      effectively suppressed or enhanced target RSNs spiking, respectively. In contrast
      to the lateralized effects on MiD cells, single M-cell spiking elicited equally
      strong depolarizations on bilateral RSNs located ventrally (MiV cells), and the
      depolarization was high enough for MiV cells to burst. Therefore, the
      morphological homology of repeated RSNs in r4-r6 and their functional M-cell
      connectivity were closely correlated, suggesting that each functional connection
      works as a functional motif during the M-cell-initiated escape. 

PMID- 24573292
TI  - Arm movements induced by electrical microstimulation in the superior colliculus
      of the macaque monkey.
AB  - Neuronal activity in the deep layers of the macaque (Macaca mulatta) superior
      colliculus (SC) and the underlying reticular formation is correlated with the
      initiation and execution of arm movements (Werner, 1993). Although the
      correlation of this activity with EMGs of proximal arm muscles is as strong as in
      motor cortex (Werner et al., 1997a; Stuphorn et al., 1999), little is known about
      the influence of electrical microstimulation in the SC on the initiation and
      trajectories of arm movements. Our experiments on three macaque monkeys clearly
      show that arm movements can be elicited by electrical microstimulation in the
      deep layers of the lateral SC and underlying reticular formation. The most
      extensively trained monkey, M1, extended his arm toward the screen in front of
      him more or less stereotypically upon electrical SC stimulation. In two other
      monkeys, M2 and M3, a larger repertoire of arm movements were elicited,
      categorized into three movement types, and compared before (M3) and after (M2 and
      M3) training: twitch (56% vs. 62%), lift (6% vs. 5%), and extend (37% vs. 32%),
      respectively. Therefore, arm movements induced by electrical stimulation in the
      monkey SC represent a further component of the functional repertoire of the SC
      using its impact on motoneurons in the spinal cord, probably via premotor neurons
      in the brainstem, as well as on structures involved in executing more complex
      movements such as target-directed reaching. Therefore, the macaque SC could be
      involved directly in the initiation, execution, and amendment of arm and hand
      movements.

PMID- 24573290
TI  - UV irradiation accelerates amyloid precursor protein (APP) processing and
      disrupts APP axonal transport.
AB  - Overexpression and/or abnormal cleavage of amyloid precursor protein (APP) are
      linked to Alzheimer's disease (AD) development and progression. However, the
      molecular mechanisms regulating cellular levels of APP or its processing, and the
      physiological and pathological consequences of altered processing are not well
      understood. Here, using mouse and human cells, we found that neuronal damage
      induced by UV irradiation leads to specific APP, APLP1, and APLP2 decline by
      accelerating their secretase-dependent processing. Pharmacological inhibition of
      endosomal/lysosomal activity partially protects UV-induced APP processing
      implying contribution of the endosomal and/or lysosomal compartments in this
      process. We found that a biological consequence of UV-induced gamma-secretase
      processing of APP is impairment of APP axonal transport. To probe the functional
      consequences of impaired APP axonal transport, we isolated and analyzed
      presumptive APP-containing axonal transport vesicles from mouse cortical
      synaptosomes using electron microscopy, biochemical, and mass spectrometry
      analyses. We identified a population of morphologically heterogeneous organelles
      that contains APP, the secretase machinery, molecular motors, and previously
      proposed and new residents of APP vesicles. These possible cargoes are enriched
      in proteins whose dysfunction could contribute to neuronal malfunction and
      diseases of the nervous system including AD. Together, these results suggest that
      damage-induced APP processing might impair APP axonal transport, which could
      result in failure of synaptic maintenance and neuronal dysfunction. 

PMID- 24573291
TI  - Anterior cingulate cortex instigates adaptive switches in choice by integrating
      immediate and delayed components of value in ventromedial prefrontal cortex.
AB  - Actions can lead to an immediate reward or punishment and a complex set of
      delayed outcomes. Adaptive choice necessitates the brain track and integrate both
      of these potential consequences. Here, we designed a sequential task whereby the
      decision to exploit or forego an available offer was contingent on comparing
      immediate value and a state-dependent future cost of expending a limited
      resource. Crucially, the dynamics of the task demanded frequent switches in
      policy based on an online computation of changing delayed consequences. We found
      that human subjects choose on the basis of a near-optimal integration of
      immediate reward and delayed consequences, with the latter computed in a
      prefrontal network. Within this network, anterior cingulate cortex (ACC) was
      dynamically coupled to ventromedial prefrontal cortex (vmPFC) when adaptive
      switches in choice were required. Our results suggest a choice architecture
      whereby interactions between ACC and vmPFC underpin an integration of immediate
      and delayed components of value to support flexible policy switching that
      accommodates the potential delayed consequences of an action. 

PMID- 24573293
TI  - Global optogenetic activation of inhibitory interneurons during epileptiform
      activity.
AB  - Optogenetic techniques provide powerful tools for bidirectional control of
      neuronal activity and investigating alterations occurring in excitability
      disorders, such as epilepsy. In particular, the possibility to specifically
      activate by light-determined interneuron populations expressing channelrhodopsin
      2 provides an unprecedented opportunity of exploring their contribution to
      physiological and pathological network activity. There are several subclasses of
      interneurons in cortical areas with different functional connectivity to the
      principal neurons (e.g., targeting their perisomatic or dendritic compartments).
      Therefore, one could optogenetically activate specific or a mixed population of
      interneurons and dissect their selective or concerted inhibitory action on
      principal cells. We chose to explore a conceptually novel strategy involving
      simultaneous activation of mixed populations of interneurons by optogenetics and
      study their impact on ongoing epileptiform activity in mouse acute hippocampal
      slices. Here we demonstrate that such approach results in a brief initial action
      potential discharge in CA3 pyramidal neurons, followed by prolonged suppression
      of ongoing epileptiform activity during light exposure. Such sequence of events
      was caused by massive light-induced release of GABA from ChR2-expressing
      interneurons. The inhibition of epileptiform activity was less pronounced if only
      parvalbumin- or somatostatin-expressing interneurons were activated by light. Our
      data suggest that global optogenetic activation of mixed interneuron populations
      is a more effective approach for development of novel therapeutic strategies for
      epilepsy, but the initial action potential generation in principal neurons needs
      to be taken in consideration. 

PMID- 24573294
TI  - Sprouting of brainstem-spinal tracts in response to unilateral motor cortex
      stroke in mice.
AB  - After a stroke to the motor cortex, sprouting of spared contralateral
      corticospinal fibers into the affected hemicord is one mechanism thought to
      mediate functional recovery. Little is known, however, about the role of the
      phylogenetically old, functionally very important brainstem-spinal systems. Adult
      mice were subjected to a unilateral photothrombotic stroke of the right motor
      cortex ablating 90% of the cross-projecting corticospinal cells. Unilateral
      retrograde tracing from the left cervical spinal hemicord devoid of its
      corticospinal input revealed widespread plastic responses in different brainstem
      nuclei 4 weeks after stroke. Whereas some nuclei showed no change or a decrease
      of their spinal projections, several parts of the medullary reticular formation
      as well as the spinally projecting raphe nuclei increased their projections to
      the cortically denervated cervical hemicord by 1.2- to 1.6-fold. The terminal
      density of corticobulbar fibers from the intact, contralesional cortex, which
      itself formed a fivefold expanded connection to the ipsilateral spinal cord,
      increased up to 1.6-fold specifically in these plastic, caudal medullary nuclei.
      A second stroke, ablating the originally spared motor cortex, resulted in the
      reappearance of the deficits that had partially recovered after the initial right
      sided stroke, suggesting dependence of recovered function on the spared cortical
      hemisphere and its direct corticospinal and indirect corticobulbospinal
      connections. 

PMID- 24573295
TI  - Neural responses to target features outside a search array are enhanced during
      conjunction but not unique-feature search.
AB  - The visual world is typically too complex to permit full apprehension of its
      content from a single fixation. Humans therefore use visual search to direct
      attention and eye movements to locations or objects of interest in cluttered
      scenes. Psychophysical investigations have revealed that observers can select
      target elements from within an array of distractors on the basis of their spatial
      location or simple features, such as color. It remains unclear, however, how
      stimuli that lie outside the current search array are represented in the visual
      system. To investigate this, we recorded continuous neural activity using EEG
      while participants searched a foveal array of colored targets and distractors,
      and ignored irrelevant objects in the periphery. Search targets were defined
      either by a unique feature within the array or by a conjunction of features.
      Objects outside the array could match the target or distractor color within the
      array, or otherwise possessed a baseline (neutral) color present only in the
      periphery. The search array and irrelevant peripheral objects flickered at unique
      rates and thus evoked distinct frequency-tagged neural oscillations. During
      conjunction but not unique-feature search, target-colored objects outside the
      array evoked enhanced activity relative to distractor-colored and neutral
      objects. The results suggest that feature-based selection applies to stimuli at
      ignored peripheral locations, but only when central targets compete with
      distractors within the array. Distractor-colored and neutral objects evoked
      equivalent oscillatory responses, suggesting that feature-based selection at
      ignored locations during visual search arises exclusively from enhancement rather
      than suppression of neural activity. 

PMID- 24573296
TI  - Mutation of 3-hydroxy-3-methylglutaryl CoA synthase I reveals requirements for
      isoprenoid and cholesterol synthesis in oligodendrocyte migration arrest, axon
      wrapping, and myelin gene expression.
AB  - Myelin membrane, which ensheaths axons, has an unusually high amount of
      cholesterol. Cholesterol influences membrane fluidity and assembles lipid-rich
      microdomains within membranes, and some studies have shown that cholesterol is
      important for myelination. How cholesterol influences the development and
      differentiation of oligodendrocytes, glial cells that make myelin, is not known
      nor is clear whether isoprenoids, which also are products of the cholesterol
      biosynthetic pathway, contribute to myelination. Through a forward genetic screen
      in zebrafish we discovered that mutation of hmgcs1, which encodes an enzyme
      necessary for isoprenoid and cholesterol synthesis, causes oligodendrocyte
      progenitor cells (OPCs) to migrate past their target axons and to fail to express
      myelin genes. Drawing on a combination of pharmacological inhibitor and rescue
      experiments, we provide evidence that isoprenoids and protein prenylation, but
      not cholesterol, are required in OPCs to halt their migration at target axons. On
      the other hand, cholesterol, but not isoprenoids, is necessary both for axon
      ensheathment and myelin gene expression. Our data reveal that different products
      of the cholesterol biosynthetic pathway have distinct roles in oligodendrocyte
      development and that they together help to coordinate directed migration, axon
      wrapping, and gene expression. 

PMID- 24573297
TI  - Postsynaptic FMRP promotes the pruning of cell-to-cell connections among
      pyramidal neurons in the L5A neocortical network.
AB  - Pruning of structural synapses occurs with development and learning. A deficit in
      pruning of cortical excitatory synapses and the resulting hyperconnectivity is
      hypothesized to underlie the etiology of fragile X syndrome (FXS) and related
      autistic disorders. However, clear evidence for pruning in neocortex and its
      impairment in FXS remains elusive. Using simultaneous recordings of pyramidal
      neurons in the layer 5A neocortical network of the wild-type (WT) mouse to
      observe cell-to-cell connections in isolation, we demonstrate here a specific
      form of "connection pruning." Connection frequency among pyramidal neurons
      decreases between the third and fifth postnatal weeks, indicating a period of
      connection pruning. Over the same interval in the FXS model mouse, the Fmr1 knock
      out (KO), connection frequency does not decrease. Therefore, connection frequency
      in the fifth week is higher in the Fmr1 KO compared with WT, indicating a state
      of hyperconnectivity. These alterations are due to postsynaptic deletion of Fmr1.
      At early ages (2 weeks), postsynaptic Fmr1 promoted the maturation of cell-to
      cell connections, but not their number. These findings indicate that impaired
      connection pruning at later ages, and not an excess of connection formation,
      underlies the hyperconnectivity in the Fmr1 KO mouse. FMRP did not appear to
      regulate synapses individually, but instead regulated cell-to-cell connectivity
      in which groups of synapses mediating a single cell-to-cell connection are
      uniformly removed, retained, and matured. Although we do not link connection
      pruning directly to the pruning of structurally defined synapses, this study
      nevertheless provides an important model system for studying altered pruning in
      FXS. 

PMID- 24573299
TI  - SPIG1 negatively regulates BDNF maturation.
AB  - We previously identified SPARC-related protein-containing immunoglobulin domains
      1 (SPIG1, also known as Follistatin-like protein 4) as one of the dorsal-retina
      specific molecules expressed in the developing chick retina. We here demonstrated
      that the knockdown of SPIG1 in the retinal ganglion cells (RGCs) of developing
      chick embryos induced the robust ectopic branching of dorsal RGC axons and failed
      to form a tight terminal zone at the proper position on the tectum. The knockdown
      of SPIG1 in RGCs also led to enhanced axon branching in vitro. However, this was
      canceled by the addition of a neutralizing antibody against brain-derived
      neurotrophic factor (BDNF) to the culture medium. SPIG1 and BDNF were colocalized
      in vesicle-like structures in cells. SPIG1 bound with the proform of BDNF
      (proBDNF) but very weakly with mature BDNF in vitro. The expression and secretion
      of mature BDNF were significantly decreased when SPIG1 was exogenously expressed
      with BDNF in HEK293T or PC12 cells. The amount of mature BDNF proteins as well as
      the tyrosine phosphorylation level of the BDNF receptor, tropomyosin-related
      kinase B (TrkB), in the hippocampus were significantly higher in SPIG1-knockout
      mice than in wild-type mice. Here the spine density of CA1 pyramidal neurons was
      consistently increased. Together, these results suggest that SPIG1 negatively
      regulated BDNF maturation by binding to proBDNF, thereby suppressing axonal
      branching and spine formation. 

PMID- 24573298
TI  - Mir-592 regulates the induction and cell death-promoting activity of p75NTR in
      neuronal ischemic injury.
AB  - The neurotrophin receptor p75(NTR) has been implicated in mediating neuronal
      apoptosis after injury to the CNS. Despite its frequent induction in pathologic
      states, there is limited understanding of the mechanisms that regulate p75(NTR)
      expression after injury. Here, we show that after focal cerebral ischemia in vivo
      or oxygen-glucose deprivation in organotypic hippocampal slices or neurons,
      p75(NTR) is rapidly induced. A concomitant induction of proNGF, a ligand for
      p75(NTR), is also observed. Induction of this ligand/receptor system is
      pathologically relevant, as a decrease in apoptosis, after oxygen-glucose
      deprivation, is observed in hippocampal neurons or slices after delivery of
      function-blocking antibodies to p75(NTR) or proNGF and in p75(NTR) and ngf
      haploinsufficient slices. Furthermore, a significant decrease in infarct volume
      was noted in p75(NTR)-/- mice compared with the wild type. We also investigated
      the regulatory mechanisms that lead to post-ischemic induction of p75(NTR). We
      demonstrate that induction of p75(NTR) after ischemic injury is independent of
      transcription but requires active translation. Basal levels of p75(NTR) in
      neurons are maintained in part by the expression of microRNA miR-592, and an
      inverse correlation is seen between miR-592 and p75(NTR) levels in the adult
      brain. After cerebral ischemia, miR-592 levels fall, with a corresponding
      increase in p75(NTR) levels. Importantly, overexpression of miR-592 in neurons
      decreases the level of ischemic injury-induced p75(NTR) and attenuates activation
      of pro-apoptotic signaling and cell death. These results identify miR-592 as a
      key regulator of p75(NTR) expression and point to a potential therapeutic
      candidate to limit neuronal apoptosis after ischemic injury. 

PMID- 24573300
TI  - Activity-dependent and activity-independent development of the axon initial
      segment.
AB  - The axon initial segment (AIS) is the site of spike initiation in neurons.
      Previous studies revealed that spatial distribution of the AIS varies greatly
      among neurons to meet their specific needs. However, when and how this
      differentiation arises is unknown. Neurons in the avian nucleus laminaris (NL)
      are binaural coincidence detectors for sound localization and show
      differentiation in the distribution of the AIS, with shorter length and a more
      distal position from the soma with an increase in tuning frequency. We studied
      these characteristics of the AIS in NL neurons of the chicken during development
      and found that the AIS differentiates in its distribution after initial
      formation, and this is driven by activity-dependent and activity-independent
      mechanisms that differentially regulate distal and proximal boundaries of the
      AIS. Before hearing onset, the ankyrinG-positive AIS existed at a wide stretch of
      proximal axon regardless of tuning frequency, but Na+ channels were only
      partially distributed within the AIS. Shortly after hearing onset, Na+ channels
      accumulated along the entire AIS, which started shortening and relocating
      distally to a larger extent in neurons with higher tuning frequencies. Ablation
      of inner ears abolished the shortening of the AIS without affecting the position
      of its proximal boundary, indicating that both distal and proximal AIS boundaries
      are disassembled during development, and the former is dependent on afferent
      activity. Thus, interaction of these activity-dependent and activity-independent
      mechanisms determines the cell-specific distribution of the AIS in NL neurons and
      plays a critical role in establishing the function of sound localization circuit.

PMID- 24573302
TI  - sp3-sp3 Coupling reactions in the synthesis of natural products and biologically
      active molecules.
AB  - This Highlight covers the current status of relatively unexplored sp(3)-sp(3)
      cross-coupling reactions with particular focus on natural product and related
      syntheses.

PMID- 24573301
TI  - Salvia miltiorrhiza increases the expression of transcription factor Foxp3 in
      experimental murine colitis.
AB  - Salvia miltiorrhiza (SM) is mainly used for the treatment of coronary heart
      disease in China, but previous studies demonstrated that it also shows anti
      inflammatory effects and the underlying mechanisms of these effects are not well
      understood. The present study aimed to investigate the effect of an injection of
      SM powder on the expression of transcription factor Foxp3 (Foxp3) in experimental
      colitis in mice. Mice were grouped and treated with SM powder for injection at
      the time of colonic instillation of trinitrobenzene sulfonic acid. Expression
      studies were performed by quantitative polymerase chain reaction and western blot
      analysis and histological studies were performed by hematoxylin and eosin
      staining. Myeloperoxidase activity was also tested for the evaluation of colitis.
      In the treated groups, the expression of Foxp3 mRNA and protein in the spleen
      were increased, the inflamed colonic lesions were relieved and the
      myeloperoxidase activity in the colon decreased significantly. Thus, it was
      demonstrated that SM exhibited its anti-inflammatory by promoting Foxp3
      expression. SM may be effective for the treatment of inflammatory disease,
      particularly for inflammatory bowel disease. 

PMID- 24573303
TI  - Crystallized and amorphous vortices in rotating atomic-molecular Bose-Einstein
      condensates.
AB  - Vortex is a topological defect with a quantized winding number of the phase in
      superfluids and superconductors. Here, we investigate the crystallized
      (triangular, square, honeycomb) and amorphous vortices in rotating atomic
      molecular Bose-Einstein condensates (BECs) by using the damped projected Gross
      Pitaevskii equation. The amorphous vortices are the result of the considerable
      deviation induced by the interaction of atomic-molecular vortices. By changing
      the atom-molecule interaction from attractive to repulsive, the configuration of
      vortices can change from an overlapped atomic-molecular vortices to carbon
      dioxide-type ones, then to atomic vortices with interstitial molecular vortices,
      and finally into independent separated ones. The Raman detuning can tune the
      ratio of the atomic vortex to the molecular vortex. We provide a phase diagram of
      vortices in rotating atomic-molecular BECs as a function of Raman detuning and
      the strength of atom-molecule interaction. 

PMID- 24573307
TI  - Reading about explanations enhances perceptions of inevitability and
      foreseeability: a cross-cultural study with Wikipedia articles.
AB  - In hindsight, people often perceive events to be more inevitable and foreseeable
      than in foresight. According to Causal Model Theory (Nestler et al. in J Exp
      Psychol Learn Mem Cogn 34: 1043-1054, 2008), causal explanations are crucial for
      such hindsight distortions to occur. The present study provides further empirical
      support for this notion but extends previous findings in several ways. First,
      ecologically valid materials were used. Second, the effect of causal information
      on hindsight distortions was investigated in the realm of previously known
      events. Third, cross-cultural differences in reasoning (analytic vs. holistic)
      were taken into account. Specifically, German and Vietnamese participants in our
      study were presented with Wikipedia articles about the nuclear power plant in
      Fukushima Daiichi, Japan. They read either the version that existed before the
      nuclear disaster unfolded (Version 1) or the article that existed 8 weeks after
      the catastrophe commenced (Version 2). Only the latter contained elaborations on
      causal antecedents and therefore provided an explanation for the disaster.
      Reading that version led participants to perceive the nuclear disaster to be more
      likely inevitable and foreseeable when compared to reading Version 1. Cultural
      background did not exert a significant effect on these perceptions. Hence,
      hindsight distortions were obtained for ecologically valid materials even if the
      event was already known. Implications and directions for future research are
      discussed.

PMID- 24573306
TI  - An investigation into membrane bound redox carriers involved in energy
      transduction mechanism in Brevibacterium linens DSM 20158 with unsequenced
      genome.
AB  - Brevibacterium linens (B. linens) DSM 20158 with an unsequenced genome can be
      used as a non-pathogenic model to study features it has in common with other
      unsequenced pathogens of the same genus on the basis of comparative proteome
      analysis. The most efficient way to kill a pathogen is to target its energy
      transduction mechanism. In the present study, we have identified the redox
      protein complexes involved in the electron transport chain of B. linens DSM 20158
      from their clear homology with the shot-gun genome sequenced strain BL2 of B.
      linens by using the SDS-Polyacrylamide gel electrophoresis coupled with nano LC
      MS/MS mass spectrometry. B. linens is found to have a branched electron transport
      chain (Respiratory chain), in which electrons can enter the respiratory chain
      either at NADH (Complex I) or at Complex II level or at the cytochrome level.
      Moreover, we are able to isolate, purify, and characterize the membrane bound
      Complex II (succinate dehydrogenase), Complex III (menaquinone cytochrome c
      reductase cytochrome c subunit, Complex IV (cytochrome c oxidase), and Complex V
      (ATP synthase) of B. linens strain DSM 20158.

PMID- 24573308
TI  - Improvement in pH sensitivity of low-temperature polycrystalline-silicon thin
      film transistor sensors using H2 sintering.
AB  - In this article, we report an improvement in the pH sensitivity of low
      temperature polycrystalline-silicon (poly-Si) thin-film transistor (TFT) sensors
      using an H2 sintering process. The low-temperature polycrystalline-silicon (LTPS)
      TFT sensor with H2 sintering exhibited a high sensitivity than that without H2
      sintering. This result may be due to the resulting increase in the number of Si
      OH2(+) and Si-O(-) bonds due to the incorporation of H in the gate oxide to
      reduce the dangling silicon bonds and hence create the surface active sites and
      the resulting increase in the number of chemical reactions at these surface
      active sites. Moreover, the LTPS TFT sensor device not only offers low cost and a
      simple fabrication processes, but the technique also can be extended to integrate
      the sensor into other systems.

PMID- 24573309
TI  - Sensor network infrastructure for a home care monitoring system.
AB  - This paper presents the sensor network infrastructure for a home care system that
      allows long-term monitoring of physiological data and everyday activities. The
      aim of the proposed system is to allow the elderly to live longer in their home
      without compromising safety and ensuring the detection of health problems. The
      system offers the possibility of a virtual visit via a teleoperated robot. During
      the visit, physiological data and activities occurring during a period of time
      can be discussed. These data are collected from physiological sensors (e.g.,
      temperature, blood pressure, glucose) and environmental sensors (e.g., motion,
      bed/chair occupancy, electrical usage). The system can also give alarms if sudden
      problems occur, like a fall, and warnings based on more long-term trends, such as
      the deterioration of health being detected. It has been implemented and tested in
      a test environment and has been deployed in six real homes for a year-long
      evaluation. The key contribution of the paper is the presentation of an
      implemented system for ambient assisted living (AAL) tested in a real
      environment, combining the acquisition of sensor data, a flexible and adaptable
      middleware compliant with the OSGistandard and a context recognition application.
      The system has been developed in a European project called GiraffPlus. 

PMID- 24573305
TI  - Transferrin receptor-mediated endocytosis: a useful target for cancer therapy.
AB  - Current cancer management strategies fail to adequately treat malignancies with
      multivariable dose-restricting factors such as systemic toxicity and multi-drug
      resistance limiting therapeutic benefit, quality of life and complete long-term
      remission rates. The targeted delivery of a therapeutic compound aims to enhance
      its circulation and cellular uptake, decrease systemic toxicity and improve
      therapeutic benefit with disease specificity. The transferrin peptide, its
      receptor and their biological significance, has been widely characterised and
      vastly relevant when applied to targeting strategies. Utilising knowledge about
      the physiological function of the transferrin-transferrin receptor complex and
      the efficiency of its receptor-mediated endocytosis provides rationale to
      continue the development of transferrin-targeted anticancer modalities.
      Furthermore, multiple studies report an upregulation in expression of the
      transferrin receptor on metastatic and drug resistant tumours, highlighting its
      selectivity to cancer. Due to the increased expression of the transferrin
      receptor in brain glioma, the successful delivery of anticancer compounds to the
      tumour site and the ability to cross the blood brain barrier has shown to be an
      important discovery. Its significance in the development of cancer-specific
      therapies is shown to be important by direct conjugation and immunotoxin studies
      which use transferrin and anti-transferrin receptor antibodies as the targeting
      moiety. Such conjugates have demonstrated enhanced cellular uptake via
      transferrin-mediated mechanisms and increased selective cytotoxicity in a number
      of cancer cell lines and tumour xenograft animal models. In addition, incubation
      of chemotherapy-insensitive cancer cells with transferrin-targeted conjugates in
      vitro has resulted in a reversal of their drug resistance. Transferrin
      immunotoxins have also shown similar promise, with a diphtheria toxin mutant
      covalently bound to transferrin (Tf-CRM107) currently involved in human clinical
      trials for the treatment of glioblastoma. Despite this, the inability to
      translate preliminary research into a clinical setting has compelled research
      into novel targeting strategies including the use of nanoparticulate theory in
      the design of drug delivery systems. The main objective of this review is to
      evaluate the importance of the transferrin-transferrin receptor complex as a
      target for cancer therapy through extensive knowledge of both the physiological
      and pathological interactions between the complex and different cell types. In
      addition, this review serves as a summary to date of direct conjugation and
      immunotoxin studies, with an emphasis on transferrin as an important targeting
      moiety in the directed delivery of anticancer therapeutic compounds. 

PMID- 24573310
TI  - Intrinsic embedded sensors for polymeric mechatronics: flexure and force sensing.
AB  - While polymeric fabrication processes, including recent advances in additive
      manufacturing, have revolutionized manufacturing, little work has been done on
      effective sensing elements compatible with and embedded within polymeric
      structures. In this paper, we describe the development and evaluation of two
      important sensing modalities for embedding in polymeric mechatronic and robotic
      mechanisms: multi-axis flexure joint angle sensing utilizing IR phototransistors,
      and a small (12 mm), three-axis force sensing via embedded silicon strain gages
      with similar performance characteristics as an equally sized metal element based
      sensor. 

PMID- 24573312
TI  - Magnetic sensing with ferrofluid and fiber optic connectors.
AB  - A simple, cost effective and sensitive fiber optic magnetic sensor fabricated
      with ferrofluid and commercially available fiber optic components is described in
      this paper. The system uses a ferrofluid infiltrated extrinsic Fabry-Perot
      interferometer (EFPI) interrogated with an infrared wavelength spectrometer to
      measure magnetic flux density. The entire sensing system was developed with
      commercially available components so it can be easily and economically reproduced
      in large quantities. The device was tested with two different ferrofluid types
      over a range of magnetic flux densities to verify performance. The sensors
      readily detected magnetic flux densities in the range of 0.5 mT to 12.0 mT with
      measurement sensitivities in the range of 0.3 to 2.3 nm/mT depending on
      ferrofluid type. Assuming a conservative wavelength resolution of 0.1 nm for
      state of the art EFPI detection abilities, the estimated achievable measurement
      resolution is on the order 0.04 mT. The inherent small size and basic structure
      complimented with the fabrication ease make it well-suited for a wide array of
      research, industrial, educational and military applications. 

PMID- 24573311
TI  - Pathlength determination for gas in scattering media absorption spectroscopy.
AB  - Gas in scattering media absorption spectroscopy (GASMAS) has been extensively
      studied and applied during recent years in, e.g., food packaging, human sinus
      monitoring, gas diffusion studies, and pharmaceutical tablet characterization.
      The focus has been on the evaluation of the gas absorption pathlength in porous
      media, which a priori is unknown due to heavy light scattering. In this paper,
      three different approaches are summarized. One possibility is to simultaneously
      monitor another gas with known concentration (e.g., water vapor), the pathlength
      of which can then be obtained and used for the target gas (e.g., oxygen) to
      retrieve its concentration. The second approach is to measure the mean optical
      pathlength or physical pathlength with other methods, including time-of-flight
      spectroscopy, frequency-modulated light scattering interferometry and the
      frequency domain photon migration method. By utilizing these methods, an average
      concentration can be obtained and the porosities of the material are studied. The
      last method retrieves the gas concentration without knowing its pathlength by
      analyzing the gas absorption line shape, which depends upon the concentration of
      buffer gases due to intermolecular collisions. The pathlength enhancement effect
      due to multiple scattering enables also the use of porous media as multipass gas
      cells for trace gas monitoring. All these efforts open up a multitude of
      different applications for the GASMAS technique. 

PMID- 24573313
TI  - A tensor-based subspace approach for bistatic MIMO radar in spatial colored
      noise.
AB  - In this paper, a new tensor-based subspace approach is proposed to estimate the
      direction of departure (DOD) and the direction of arrival (DOA) for bistatic
      multiple-input multiple-output (MIMO) radar in the presence of spatial colored
      noise. Firstly, the received signals can be packed into a third-order measurement
      tensor by exploiting the inherent structure of the matched filter. Then, the
      measurement tensor can be divided into two sub-tensors, and a cross-covariance
      tensor is formulated to eliminate the spatial colored noise. Finally, the signal
      subspace is constructed by utilizing the higher-order singular value
      decomposition (HOSVD) of the cross-covariance tensor, and the DOD and DOA can be
      obtained through the estimation of signal parameters via rotational invariance
      technique (ESPRIT) algorithm, which are paired automatically. Since the
      multidimensional inherent structure and the cross-covariance tensor technique are
      used, the proposed method provides better angle estimation performance than
      Chen's method, the ESPRIT algorithm and the multi-SVD method. Simulation results
      confirm the effectiveness and the advantage of the proposed method. 

PMID- 24573314
TI  - New players in haemostasis and thrombosis.
AB  - The blood coagulation cascade is essential for haemostasis, but excessive
      activation can cause thrombosis. Importantly, recent studies have identified
      factors that contribute to thrombosis but not haemostasis. These include factor
      XII (FXII), tissue factor-positive microparticles (MPs) and neutrophil
      extracellular traps (NETs). Studies have shown that FXII plays a role in
      thrombosis but not haemostasis. FXII is activated in vivo by a variety of
      negatively-charged polyphosphates, which include extracellular RNA, DNA and
      inorganic polyphosphate (PolyP) that are released during cell damage and
      infection. These findings have led to the development of nucleic acid-binding
      polymers as a new class of anticoagulant drug. Other studies have analysed the
      role of MPs in experimental thrombosis. MPs are small membrane vesicles released
      from activated or apoptotic cells. We and others have found that tissue factor
      positive MPs enhance thrombosis in mouse models and are elevated in the plasma of
      pancreatic cancer patients. Finally, NETs have been shown to contribute to
      experimental venous thrombosis in mouse models and are present in human thrombi.
      NETs are composed of chromatin fibers that are released from neutrophils
      undergoing cell death. NETs can capture platelets and increase fibrin deposition.
      The recent advances in our understanding of the factors contributing to
      thrombosis in animal models provide new opportunities for the development of
      safer anticoagulant drugs. 

PMID- 24573317
TI  - The changing epidemiology of HIV-related chronic kidney disease in the era of
      antiretroviral therapy.
AB  - The epidemiology of kidney disease in HIV-infected individuals has changed
      significantly since the introduction of combination antiretroviral therapy (cART)
      in the mid 1990s. HIV-associated nephropathy (HIVAN), an aggressive form of
      collapsing focal segmental glomerulosclerosis (FSGS) caused by direct HIV
      infection of the kidney in a genetically susceptible host, emerged early in the
      HIV epidemic as a leading cause of end-stage renal disease. With the widespread
      use of cART, HIVAN is increasingly rare in populations with access to care, and
      the spectrum of HIV-related chronic kidney disease now reflects the growing
      burden of comorbid disease in the aging HIV population. Nonetheless, available
      data suggest that both HIV infection and cART nephrotoxicity continue to
      contribute to the increased risk of chronic kidney disease in HIV-infected
      individuals in the United States and Europe. Despite the genetic susceptibility
      to HIVAN in individuals of West African descent, limited data are available to
      define the prevalence and spectrum of HIV-related kidney disease in sub-Saharan
      Africa, which is home to two-thirds of the world's HIV population. In this mini
      review, we characterize the changing epidemiology of HIV-related chronic kidney
      disease in Western nations and in sub-Saharan Africa. 

PMID- 24573318
TI  - BPA from dental resin material: where are we going with restorative and
      preventive dental biomaterials?

PMID- 24573315
TI  - Advances in the pathophysiology of pre-eclampsia and related podocyte injury.
AB  - Pre-eclampsia is a pregnancy-specific hypertensive disorder that may lead to
      serious maternal and fetal complications. It is a multisystem disease that is
      commonly, but not always, accompanied by proteinuria. Its cause(s) remain
      unknown, and delivery remains the only definitive treatment. It is increasingly
      recognized that many pathophysiological processes contribute to this syndrome,
      with different signaling pathways converging at the point of systemic endothelial
      dysfunction, hypertension, and proteinuria. Different animal models of pre
      eclampsia have proven utility for specific aspects of pre-eclampsia research, and
      offer insights into pathophysiology and treatment possibilities. Therapeutic
      interventions that specifically target these pathways may optimize pre-eclampsia
      management and may improve fetal and maternal outcomes. In addition, recent
      findings regarding placental, endothelial, and podocyte pathophysiology in pre
      eclampsia provide unique and exciting possibilities for improved diagnostic
      accuracy. Emerging evidence suggests that testing for urinary podocytes or their
      markers may facilitate the prediction and diagnosis of pre-eclampsia. In this
      review, we explore recent research regarding placental, endothelial, and podocyte
      pathophysiology. We further discuss new signaling and genetic pathways that may
      contribute to pre-eclampsia pathophysiology, emerging screening and diagnostic
      strategies, and potential targeted interventions. 

PMID- 24573319
TI  - Lack of supportive evidence for the use of immunohistochemical staining to
      identify occult regional lymph node metastases in primary lung cancer.
AB  - Immunohistochemical (IHC) staining for the identification of nodal occult
      metastases (OM), not detected by routine histological examination, has been
      proposed for improved staging, prognostication and decision of adjuvant treatment
      in surgically treated primary lung cancer. In a prospective study, we analysed
      178 cases of primary lung cancer stage I-III (N0-N1) for OM by immunostaining
      lymph node tissue using a broad-spectrum anti-cytokeratin antibody. OM were found
      in 7 (4 %) of the 178 cases. Using Kaplan-Meier analysis, overall survival was
      not significantly different between cases with stage I and cases upstaged to
      stage II because of OM (n = 3), or between cases with stage II and cases upstaged
      to stage III (n = 4). Likewise, the presence of OM was not significantly
      correlated with overall survival in univariable or multivariable Cox proportional
      hazards regression models, also when disregarding OM <0.2 mm in size. Given the
      low frequency of OM and lack of significant impact on survival in our study, the
      justification for including IHC staining of lymph nodes in lung cancer in
      clinical practise does not appear convincing. Moreover, we report several
      potential pitfalls in the use of broad-spectrum cytokeratin IHC staining for OM
      detection, for example staining of intra-nodal mesothelial cells.

PMID- 24573320
TI  - Retinitis pigmentosa-associated rhodopsin mutant T17M induces endoplasmic
      reticulum (ER) stress and sensitizes cells to ER stress-induced cell death.
AB  - Retinitis pigmentosa (RP) is a group of inherited diseases that primarily affect
      light-sensitive rods and cones in the retina. Rhodopsin mutations, including the
      T17M mutation, are associated with the autosomal dominant form of retinitis
      pigmentosa (ADRP) and have been linked to abnormal protein folding. However, the
      molecular mechanisms underlying T17M rhodopsin-induced retinal degeneration are
      yet to be elucidated. In the present study, Human embryonic kidney (HEK) 293 and
      ARPE-19 cells were transfected with myc-tagged wild-type (WT) and T17M rhodopsin
      constructs. Cells were fixed and stained with anti-myc antibodies and the
      localization of WT and T17M rhodopsin was visualized using immunofluorescence
      microscopy. Turnover rates of WT and T17M rhodopsin were measured using western
      blot analysis. In addition, endoplasmic reticulum (ER) stress-induced cell death
      was analyzed in WT and T17M rhodopsin-transfected cells using nuclear staining.
      Misfolded T17M rhodopsin was observed to be abnormally localized in the ER, while
      WT rhodopsin was predominantly found at the plasma membrane. Protein turnover
      analysis revealed that T17M rhodopsin was more rapidly degraded by proteasomes
      than WT rhodopsin. Furthermore, overexpression of T17M rhodopsin was observed to
      induce cell death and increase cytotoxicity; predisposing cells to ER stress
      induced cell death. These findings show novel insight into the properties of T17M
      rhodopsin and highlight the role of ER stress in T17M-associated RP. 

PMID- 24573321
TI  - Synthesis of wurtzite-zincblende Cu2ZnSnS4 and Cu2ZnSnSe4 nanocrystals: insight
      into the structural selection of quaternary and ternary compounds influenced by
      binary nuclei.
AB  - Nearly monodispersed wurtzite-dominant Cu2ZnSnS4 and zincblende-dominant
      Cu2ZnSnSe4 nanocrystals were successfully synthesized by mixing metal salts with
      heated thiourea or selenourea in oleylamine. A perspective of the structural
      relationship between quaternary and ternary semiconductors was investigated
      through the application of different anion sources to prepare Cu2SnS3 and
      Cu2SnSe3 nanocrystals. Investigations on copper-based binary compounds found that
      CuSe (or CuS) and Cu2Se (or Cu1.96S, Cu9S5) nuclei were primarily responsible for
      the formation of zincblende or wurtzite structures, respectively. Further
      management over these binary intermediates corresponded to slight structural
      transformations of the quaternary nanocrystals which could be observed not only
      in XRD patterns, but from optical and electrical properties as well. According to
      these results, Cu2ZnGeS4 nanocrystals with wurtzite-dominant structures were
      first reported using SC(NH2)2, which also verified that the binary semiconductors
      are the determinative factors. 

PMID- 24573316
TI  - Relation between BK-alpha/beta4-mediated potassium secretion and ENaC-mediated
      sodium reabsorption.
AB  - The large-conductance, calcium-activated BK-alpha/beta4 potassium channel,
      localized to the intercalated cells of the distal nephron, mediates potassium
      secretion during high-potassium, alkaline diets. Here we determine whether BK
      alpha/beta4-mediated potassium transport is dependent on epithelial sodium
      channel (ENaC)-mediated sodium reabsorption. We maximized sodium-potassium
      exchange in the distal nephron by feeding mice a low-sodium, high-potassium diet.
      Wild-type and BK-beta4 knockout mice were maintained on a low-sodium, high
      potassium, alkaline diet or a low-sodium, high-potassium, acidic diet for 7-10
      days. Wild-type mice maintained potassium homeostasis on the alkaline, but not
      acid, diet. BK-beta4 knockout mice could not maintain potassium homeostasis on
      either diet. During the last 12 h of diet, wild-type mice on either a regular,
      alkaline, or an acid diet, or knockout mice on an alkaline diet, were
      administered amiloride (an ENaC inhibitor). Amiloride enhanced sodium excretion
      in all wild-type and knockout groups to similar values; however, amiloride
      diminished potassium excretion by 59% in wild-type but only by 33% in knockout
      mice on an alkaline diet. Similarly, amiloride decreased the trans-tubular
      potassium gradient by 68% in wild-type but only by 42% in knockout mice on an
      alkaline diet. Amiloride treatment equally enhanced sodium excretion and
      diminished potassium secretion in knockout mice on an alkaline diet and wild-type
      mice on an acid diet. Thus, the enhanced effect of amiloride on potassium
      secretion in wild-type compared to knockout mice on the alkaline diet clarify a
      BK- alpha/beta4-mediated potassium secretory pathway in intercalated cells driven
      by ENaC-mediated sodium reabsorption linked to bicarbonate secretion. 

PMID- 24573322
TI  - LincRNA-p21 enhances the sensitivity of radiotherapy for human colorectal cancer
      by targeting the Wnt/beta-catenin signaling pathway.
AB  - Recent studies show that long intergenic noncoding RNA-p21 (lincRNA-p21) is
      aberrantly expressed in several types of cancer, including colorectal cancer
      (CRC), one of the most common cancers in the world. Radiotherapy is considered as
      a standard preoperative treatment approach to reduce local recurrence for local
      advanced rectal cancer. However, a considerable number of rectal cancers are
      resistant to radiotherapy. In the present study, we evaluated the role of lincRNA
      p21 in radiotherapy for CRC and detected the possible molecular mechanism. By
      expression profile analysis, we demonstrated that lincRNA-p21 decreases in CRC
      cell lines and tissue samples, which contributes to the elevation of beta-catenin
      in CRC. We further showed that lincRNA-p21 increases following X-ray treatment,
      and enforced expression of the lincRNA enhances the sensitivity of radiotherapy
      for CRC by promoting cell apoptosis. Suppression of the beta-catenin signaling
      pathway and elevation of the pro-apoptosis gene Noxa expression may help explain
      the role of lincRNA-p21 in CRC radiotherapy. The present study not only deepens
      our understanding of the mechanism of radiotherapy for CRC, but it also provides
      a potential target for CRC radiotherapy. 

PMID- 24573323
TI  - Protective effect of apigenin against oxidative stress-induced damage in
      osteoblastic cells.
AB  - Apigenin, a plant-derived flavonoid, was investigated to determine whether it
      could influence hydrogen peroxide (H2O2)-induced oxidative damage and cellular
      dysfunction in the MC3T3-E1 mouse osteoblastic cell line. In the present study,
      osteoblastic cells were treated with H2O2 in the presence or absence of apigenin.
      Cell viability, apoptosis, reactive oxygen species (ROS) production and
      mitochondrial membrane potential (DeltaPsim) were subsequently examined. It was
      observed that H2O2 reduced cell survival and DeltaPsim, while it markedly
      increased the intracellular levels of ROS and apoptosis. However, pretreatment of
      cells with apigenin attenuated all the H2O2-induced effects. The antioxidants,
      catalase and N-acetyl-L-cysteine (NAC) also prevented H2O2-induced oxidative cell
      damage. In addition, treatment with apigenin resulted in a significant elevation
      of osteoblast differentiation genes including alkaline phosphatase (ALP),
      collagen, osteopontin (OPN), osteoprotegerin (OPG), bone sialoprotein (BSP),
      osterix (OSX) and osteocalcin (OC) and bone morphogenetic proteins (BMPs) genes
      (BMP2, BMP4 and BMP7). In the mechanistic studies of cell signaling by the
      antioxidative potential of apigenin, it was found that apigenin activated the
      H2O2-induced decreased expression of phosphatidylinositol 3'-kinase (PI3K),
      protein kinase B2 (AKT2) genes and extracellular signal-related kinase (EPK) 2,
      which are key regulators of survival-related signaling pathways. By contrast,
      there were no changes in the expression of nuclear facor-kappaB (NF-kappaB) and c
      Jun N-terminal kinase (JNK) gene exposed to H2O2 in the present study. Apigenin
      also upregulated the gene expression of antioxidant enzymes, superoxide dismutase
      (SOD) 1, SOD2 and glutathione peroxidase (GPx) 1. Taken together, these results
      suggested that apigenin attenuated oxidative-induced cell damage in osteoblastic
      cells and may be useful for the treatment of oxidative-related bone disease.

PMID- 24573324
TI  - Diagnostic accuracy of short-time inversion recovery sequence in Graves'
      Ophthalmopathy before and after prednisone treatment.
AB  - INTRODUCTION: In Graves' Ophthalmopathy, it is important to distinguish active
      inflammatory phase, responsive to immunosuppressive treatment, from fibrotic
      unresponsive inactive one. The purpose of this study is, first, to identify the
      relevant orbital magnetic resonance imaging signal intensities before treatment,
      so to classify patients according to their clinical activity score (CAS),
      discriminating inactive (CAS < 3) from active Graves' Ophthalmopathy (GO) (CAS >
      3) subjects and, second, to follow post-steroid treatment disease. METHODS: An
      observational study was executed on 32 GO consecutive patients in different
      phases of disease, based on clinical and orbital Magnetic Resonance Imaging
      parameters, compared to 32 healthy volunteers. Orbital Magnetic Resonance Imaging
      was performed on a 1.5 tesla Magnetic Resonance Unit by an experienced
      neuroradiologist blinded to the clinical examinations. RESULTS: In pre-therapy
      patients, compared to controls, a medial rectus muscle statistically significant
      signal intensity ratio (SIR) in short-time inversion recovery (STIR) (long TR/TE)
      sequence was found, as well as when comparing patients before and after
      treatment, both medial and inferior rectus muscle SIR resulted significantly
      statistically different in STIR. These increased outcomes explain the
      inflammation oedematous phase of disease, moreover after steroid administration,
      compared to controls; patients presented lack of that statistically significant
      difference, thus suggesting treatment effectiveness. CONCLUSION: In our study, we
      proved STIR signal intensities increase in inflammation oedematous phase,
      confirming STIR sequence to define active phase of disease with more sensibility
      and reproducibility than CAS alone and to evaluate post-therapy involvement.

PMID- 24573325
TI  - Respiratory syncytial virus-related encephalitis: magnetic resonance imaging
      findings with diffusion-weighted study: response to a "letter to the editor".

PMID- 24573326
TI  - Improved reversibility in lithium-oxygen battery: understanding elementary
      reactions and surface charge engineering of metal alloy catalyst.
AB  - Most Li-O2 batteries suffer from sluggish kinetics during oxygen evolution
      reactions (OERs). To overcome this drawback, we take the lesson from other
      catalysis researches that showed improved catalytic activities by employing metal
      alloy catalysts. Such research effort has led us to find Pt3Co nanoparticles as
      an effective OER catalyst in Li-O2 batteries. The superior catalytic activity was
      reflected in the substantially decreased overpotentials and improved cycling/rate
      performance compared to those of other catalysts. Density functional theory
      calculations suggested that the low OER overpotentials are associated with the
      reduced adsorption strength of LiO2 on the outermost Pt catalytic sites. Also,
      the alloy catalyst generates amorphous Li2O2 conformally coated around the
      catalyst and thus facilitates easier decomposition and higher reversibility. This
      investigation conveys an important message that understanding elementary
      reactions and surface charge engineering of air-catalysts are one of the most
      effective approaches in resolving the chronic sluggish charging kinetics in Li-O2
      batteries. 

PMID- 24573328
TI  - Actinomycetospora atypica sp. nov., a novel soil actinomycete and emended
      description of the genus Actinomycetospora.
AB  - A novel actinomycete, designated strain NEAU-st4(T), was isolated from a soil
      sample collected from Shaanxi province, Northwest China and characterized using a
      polyphasic approach. 16S rRNA gene sequence analysis revealed that strain NEAU
      st4(T) has the highest sequence similarities with Actinomycetospora rishiriensis
      RI109-Li102(T) (99.4 %), Actinomycetospora corticicola 014-5(T) (99.1 %),
      Actinomycetospora chiangmaiensis YIM 0006(T) (98.8 %) and Actinomycetospora
      iriomotensis IR73-Li102(T) (98.2 %). However, the low level of DNA-DNA
      relatedness differentiated strain NEAU-st4(T) from its closest phylogenetic
      neighbours. The main chemotaxonomic properties of strain NEAU-st4(T), such as the
      diamino acid of the peptidoglycan, the whole-cell hydrolysates, the predominant
      menaquinones and the phospholipid profile, supported its classification within
      the genus Actinomycetospora. The distinctive morphology of this strain compared
      with that of other members in the genus Actinomycetospora is the formation of
      sporangia directly on the substrate hyphae. Phenotypic and genotypic differences
      also allowed the distinction of the strain from closely related species.
      Consequently, strain NEAU-st4(T) represents a new species of the genus
      Actinomycetospora, for which the name Actinomycetospora atypica sp. nov. is
      proposed. The type strain is NEAU-st4(T) (=CGMCC 4.7093(T) = DSM 45873(T)). 

PMID- 24573327
TI  - Halocynthiibacter namhaensis gen. nov., sp. nov., a novel alphaproteobacterium
      isolated from sea squirt Halocynthia roretzi.
AB  - A Gram-negative, non-motile and rod-shaped bacterial strain, designated RA2-3(T),
      was isolated from a sea squirt (Halocynthia roretzi) collected from the South
      Sea, Korea, and its taxonomic position was investigated by using a polyphasic
      approach. Strain RA2-3(T) was observed to grow optimally at 25  degrees C, at pH
      7.0-7.5 and in the presence of 2 % (w/v) NaCl. Strain RA2-3(T) exhibited the
      highest 16S rRNA gene sequence similarity values to the type strains of
      Litoreibacter meonggei (95.7 %), Planktotalea frisia (95.6 %), Thalassobius
      gelatinovorus (95.5 %) and Pelagicola litoralis (95.4 %). A neighbour-joining
      phylogenetic tree based on 16S rRNA gene sequences revealed that strain RA2-3(T)
      clustered with the type strains of Planktotalea frisia, Pelagicola litoralis,
      Pacificibacter maritimus and Roseovarius marinus. Strain RA2-3(T) was found to
      contain Q-10 as the predominant ubiquinone and C18:1 omega7c as the major fatty
      acid. The major polar lipids detected in strain RA2-3(T) were
      phosphatidylcholine, phosphatidylglycerol, one unidentified aminolipid and one
      unidentified lipid. The DNA G+C content of strain RA2-3(T) was 52.9 mol%. On the
      basis of the phylogenetic, chemotaxonomic and phenotypic properties, strain RA2
      3(T) is considered to represent a new genus and species within the family
      Rhodobacteraceae, for which the name Halocynthiibacter namhaensis gen. nov., sp.
      nov. is proposed. The type strain of H. namhaensis is RA2-3(T) (=KCTC
      32362(T)=NBRC 109999(T)). 

PMID- 24573329
TI  - The effect of nanoscale surface curvature on the oligomerization of surface-bound
      proteins.
AB  - The influence of surface topography on protein conformation and association is
      used routinely in biological cells to orchestrate and coordinate biomolecular
      events. In the laboratory, controlling the surface curvature at the nanoscale
      offers new possibilities for manipulating protein-protein interactions and
      protein function at surfaces. We have studied the effect of surface curvature on
      the association of two proteins, alpha-lactalbumin (alpha-LA) and beta
      lactoglobulin (beta-LG), which perform their function at the oil-water interface
      in milk emulsions. To control the surface curvature at the nanoscale, we have
      used a combination of polystyrene (PS) nanoparticles (NPs) and ultrathin PS films
      to fabricate chemically pure, hydrophobic surfaces that are highly curved and are
      stable in aqueous buffer. We have used single-molecule force spectroscopy to
      measure the contour lengths Lc for alpha-LA and beta-LG adsorbed on highly curved
      PS surfaces (NP diameters of 27 and 50 nm, capped with a 10 nm thick PS film),
      and we have compared these values in situ with those measured for the same
      proteins adsorbed onto flat PS surfaces in the same samples. The Lc distributions
      for beta-LG adsorbed onto a flat PS surface contain monomer and dimer peaks at 60
      and 120 nm, respectively, while alpha-LA contains a large monomer peak near 50 nm
      and a dimer peak at 100 nm, with a tail extending out to 200 nm, corresponding to
      higher order oligomers, e.g. trimers and tetramers. When beta-LG or alpha-LA is
      adsorbed onto the most highly curved surfaces, both monomer peaks are shifted to
      much smaller values of Lc. Furthermore, for beta-LG, the dimer peak is strongly
      suppressed on the highly curved surface, whereas for alpha-LA the trimer and
      tetramer tail is suppressed with no significant change in the dimer peak. For
      both proteins, the number of higher order oligomers is significantly reduced as
      the curvature of the underlying surface is increased. These results suggest that
      the surface curvature provides a new method of manipulating protein-protein
      interactions and controlling the association of adsorbed proteins, with
      applications to the development of novel biosensors. 

PMID- 24573330
TI  - Genome metabolome integrated network analysis to uncover connections between
      genetic variants and complex traits: an application to obesity.
AB  - Current studies of phenotype diversity by genome-wide association studies (GWAS)
      are mainly focused on identifying genetic variants that influence level changes
      of individual traits without considering additional alterations at the system
      level. However, in addition to level alterations of single phenotypes,
      differences in association between phenotype levels are observed across different
      physiological states. Such differences in molecular correlations between states
      can potentially reveal information about the system state beyond that reported by
      changes in mean levels alone. In this study, we describe a novel methodological
      approach, which we refer to as genome metabolome integrated network analysis
      (GEMINi) consisting of a combination of correlation network analysis and genome
      wide correlation study. The proposed methodology exploits differences in
      molecular associations to uncover genetic variants involved in phenotype
      variation. We test the performance of the GEMINi approach in a simulation study
      and illustrate its use in the context of obesity and detailed quantitative
      metabolomics data on systemic metabolism. Application of GEMINi revealed a set of
      metabolic associations which differ between normal and obese individuals. While
      no significant associations were found between genetic variants and body mass
      index using a standard GWAS approach, further investigation of the identified
      differences in metabolic association revealed a number of loci, several of which
      have been previously implicated with obesity-related processes. This study
      highlights the advantage of using molecular associations as an alternative
      phenotype when studying the genetic basis of complex traits and diseases. 

PMID- 24573331
TI  - Simultaneous reconstruction of evolutionary history and epidemiological dynamics
      from viral sequences with the birth-death SIR model.
AB  - The evolution of RNA viruses, such as human immunodeficiency virus (HIV),
      hepatitis C virus and influenza virus, occurs so rapidly that the viruses'
      genomes contain information on past ecological dynamics. Hence, we develop a
      phylodynamic method that enables the joint estimation of epidemiological
      parameters and phylogenetic history. Based on a compartmental susceptible
      infected-removed (SIR) model, this method provides separate information on
      incidence and prevalence of infections. Detailed information on the interaction
      of host population dynamics and evolutionary history can inform decisions on how
      to contain or entirely avoid disease outbreaks. We apply our birth-death SIR
      method to two viral datasets. First, five HIV type 1 clusters sampled in the UK
      between 1999 and 2003 are analysed. The estimated basic reproduction ratios range
      from 1.9 to 3.2 among the clusters. All clusters show a decline in the growth
      rate of the local epidemic in the middle or end of the 1990s. The analysis of a
      hepatitis C virus genotype 2c dataset shows that the local epidemic in the
      Cordoban city Cruz del Eje originated around 1906 (median), coinciding with an
      immigration wave from Europe to central Argentina that dates from 1880 to 1920.
      The estimated time of epidemic peak is around 1970. 

PMID- 24573332
TI  - Lag, lock, sync, slip: the many 'phases' of coupled flagella.
AB  - In a multitude of life's processes, cilia and flagella are found indispensable.
      Recently, the biflagellated chlorophyte alga Chlamydomonas has become a model
      organism for the study of ciliary motility and synchronization. Here, we use high
      speed, high-resolution imaging of single pipette-held cells to quantify the rich
      dynamics exhibited by their flagella. Underlying this variability in behaviour
      are biological dissimilarities between the two flagella-termed cis and trans,
      with respect to a unique eyespot. With emphasis on the wild-type, we derive limit
      cycles and phase parametrizations for self-sustained flagellar oscillations from
      digitally tracked flagellar waveforms. Characterizing interflagellar phase
      synchrony via a simple model of coupled oscillators with noise, we find that
      during the canonical swimming breaststroke the cis flagellum is consistently
      phase-lagged relative to, while remaining robustly phase-locked with, the trans
      flagellum. Transient loss of synchrony, or phase slippage, may be triggered
      stochastically, in which the trans flagellum transitions to a second mode of
      beating with attenuated beat envelope and increased frequency. Further,
      exploiting this alga's ability for flagellar regeneration, we mechanically
      induced removal of one or the other flagellum of the same cell to reveal a
      striking disparity between the beatings of the cis and trans flagella, in
      isolation. These results are evaluated in the context of the dynamic coordination
      of Chlamydomonas flagella. 

PMID- 24573334
TI  - Impact of adherence to best practice guidelines on the diagnostic and assessment
      services for autism spectrum disorder.
AB  - Despite their range and complexity, adherence to Scottish Intercollegiate
      Guidelines Network guideline for the diagnosis and assessment of autism spectrum
      disorders (ASD) was shown to be high within child development and specialist
      diagnostic clinics serving a geographical cohort of children diagnosed under the
      age of 7 years. A retrospective analysis of comprehensive clinical notes
      demonstrated that the recommended discretionary use of structured history
      instruments was increased after medical training (p = 0.003). 56% (51/90) of
      children received the diagnosis of ASD at their initial specialist appointment.
      51% underwent the recommended discretionary structured observational instrument.
      This further assessment was more likely to be required for older children in the
      reaudited group (p = 0.001). The implications for service capacity planning when
      delivering best practice recommendations are discussed.

PMID- 24573335
TI  - Using Portable Video Modeling Technology to Increase the Compliment Behaviors of
      Children with Autism During Athletic Group Play.
AB  - A multiple baseline design across participants was used to examine the effects of
      a portable video modeling intervention delivered in the natural environment on
      the verbal compliments and compliment gestures demonstrated by five children with
      autism. Participants were observed playing kickball with peers and adults. In
      baseline, participants demonstrated few compliment behaviors. During
      intervention, an iPad((r)) was used to implement the video modeling treatment
      during the course of the athletic game. Viewing the video rapidly increased the
      verbal compliments participants gave to peers. Participants also demonstrated
      more response variation after watching the videos. Some generalization to an
      untrained activity occurred and compliment gestures also occurred. Results are
      discussed in terms of contributions to the literature. 

PMID- 24573336
TI  - A preliminary investigation of the Spence Children's Anxiety Parent Scale as a
      screening tool for anxiety in young people with autism spectrum disorders.
AB  - Despite high rates of clinically elevated anxiety difficulties in children and
      adolescents with autism spectrum disorders (ASDs), very few studies have
      systematically examined the usefulness of commonly used caregiver report anxiety
      screening tools with this population. This study investigated the use of the
      Spence Children's Anxiety Scale-Parent version (SCAS-P) as a screening tool for
      anxiety disorders when compared to a standardized DSM-IV-TR-based clinical
      interview, the Kiddie-Schedule for Schizophrenia and Affective Disorders-Present
      and Lifetime version (K-SADS-PL). Thirty-two caregivers of youth with a clinical
      diagnosis of ASD (mean age 10.3 years) attending a specialist autism school
      participated in this study. They first completed the SCAS-P, a measure of
      adaptive functioning and a checklist of other emotional and behavioral
      difficulties. They were then interviewed with the K-SADS-PL. Internal consistency
      for the SCAS Total score was .88, but Cronbach's alphas were <.70 in three of the
      six SCAS-P subscales. The sensitivity, specificity, positive predictive value
      (PPV) and negative predictive value (NPV) of the SCAS-P against K-SADS diagnosis
      were .75, .71, .27, and .95, respectively. All values were >.70, except for the
      PPV. Evidence of convergent validity between the SCAS-P, K-SADS-PL and DBC
      anxiety subscale was also found. The high false positive rates notwithstanding,
      the preliminary data of acceptable to excellent sensitivity, specificity and NPV
      values tentatively suggest that the SCAS-P may be useful for screening non-help
      seeking young people with ASD for elevated anxiety symptoms. Further replication
      in larger studies is needed and ways in which the SCAS-P could be further
      developed and investigated for use with youth with ASD are discussed. 

PMID- 24573341
TI  - Mesenchymal stem cell-based developmental endothelial locus-1 gene therapy for
      acute lung injury induced by lipopolysaccharide in mice.
AB  - Studies have suggested that bone marrow-derived mesenchymal stem cells (MSCs) may
      be used as a tool for gene therapy. Developmental endothelial locus-1 (Del-1) is
      a critical factor for cell migration and infiltration via the inhibition of the
      function of a major leukocyte adhesion receptor LFA-1 which prevents leukocyte
      adhesion to the endothelium. In the present study, we hypothesized that MSC-based
      Del-1 gene therapy may have potential therapeutic applications for
      lipopolysaccharide (LPS)-induced lung injury. The MSCs in the present assay were
      isolated from 6 week-old male mice. In order to investigate the therapeutic
      effect of the Del-1 gene on LPS-induced ALI mice, a lentivirus vector containing
      the Del-1 gene was constructed and transduced into the MSCs. In the in vivo
      assay, we induced lung injury with LPS injection and treated mice with different
      groups of MSCs, and compared with groups treated with MSCs alone, we observed
      that the administration with MSCs carrying Del-1 (MSCs-Del1) markedly alleviated
      the LPS-induced lung injury. There were significant decreases in the number of
      neutrophils in bronchoalveolar lavage (BAL) and the serum levels of TNF-alpha and
      IL-6 in the Del-1-expressed MSC-treated mice. Furthermore, compared with MSCs
      treated alone, Del1-MSC-treated mice also exhibited low lung injury scores, high
      protein concentrations and myeloperoxidase activity. In conclusion, treatment
      with Del-1-expressed MSCs significantly decreases the severity of endotoxin
      induced acute lung injury and the level of inflammatory cytokines in mice.

PMID- 24573337
TI  - Predicting cooperative drug effects through the quantitative cellular profiling
      of response to individual drugs.
AB  - Quantitative prediction of cellular responses to drugs and drug combinations is a
      challenging and valuable topic in pharmaceutical research. In the past decade,
      microarray technology has become a routine tool for monitoring genome-wide
      expression changes and has been widely adopted for exploring drug response in the
      pharmaceutical field. However, how to predict the synergistic effect of drug
      combinations using microarray data is a challenging task. In this article, we
      report a simple prediction framework based on the genome-wide and quantitative
      profiling of cellular responses to individual drugs. By exploring the
      differential expression profiles, our correlation-based strategy can reveal the
      synergistic effects of drug combinations. The comparison with gold-standard
      experimental results demonstrates the strengths and weaknesses in relation to
      prediction based only on cellular response to individual drugs. Specifically, the
      prediction strategy may work for a drug combination whose individual drugs show
      related transcriptomic mechanisms but not for others. 

PMID- 24573343
TI  - Layered double hydroxide supported gold nanoclusters by glutathione-capped Au
      nanoclusters precursor method for highly efficient aerobic oxidation of alcohols.
AB  - M3Al-layered double hydroxide (LDH, M = Mg, Ni, Co) supported Au nanoclusters
      (AuNCs) catalysts have been prepared for the first time by using water-soluble
      glutathione-capped Au nanoclusters as precursor. Detailed characterizations show
      that the ultrafine Au nanoclusters (ca. 1.5 +/- 0.6 nm) were well dispersed on
      the surface of LDH with a loading of Au below ~0.23 wt% upon synergetic
      interaction between AuNCs and M3Al-LDH. AuNCs/Mg3Al-LDH-0.23 exhibits much higher
      catalytic performance for the oxidation of 1-phenylethanol in toluene than
      Au/Mg3Al-LDH(DP) by the conventional deposition precipitation method and can be
      applied for a wide range of alcohols without basic additives. This catalyst can
      also be reused without loss of activity or selectivity. The AuNCs/M(= Ni, Co)3Al
      LDH catalysts present even higher alcohol oxidation activity than AuNCs/Mg3Al
      LDH. Particularly, AuNCs/Ni3Al-LDH-0.22 exhibits the highest activity (46 500 h(
      1)) for the aerobic oxidation of 1-phenylethanol under solvent-free conditions
      attributed to its strongest Au-support synergy. The excellent activity and
      stability of AuNCs/M3Al-LDH catalysts render these materials promising candidates
      for green base-free selective oxidation of alcohols by molecular oxygen. 

PMID- 24573342
TI  - Adherence to lifestyle modifications after a cardiac rehabilitation program and
      endothelial progenitor cells. A six-month follow-up study.
AB  - An increase of endothelial progenitor cells (EPCs) among acute myocardial
      infarction (AMI) patients participating in a cardiac rehabilitation (CR) program
      has been reported, but no data on the impact of adherence to lifestyle
      recommendations provided during a CR program on EPCs are available. It was our
      aim to investigate the effect of adherence to lifestyle recommendations on EPCs,
      inflammatory and functional parameters after six months of a CR program in AMI
      patients. In 110 AMI patients (90 male/20 female; mean age 57.9 +/- 9.4 years)
      EPCs, high sensitivity C-reactive protein (hsCRP), N-terminal pro-brain
      natriuretic peptide (NT-ProBNP) levels, and cardiopulmonary testings were
      determined at the end of the CR (T1) and at a six-month follow-up (T2). At T2 we
      administered a questionnaire assessing dietary habits and physical activity. At
      T2, we observed a decrease of EPCs (p<0.05), of hsCRP (p=0.009) and of NT-ProBNP
      (p<0.0001). Patient population was divided into three categories by Healthy
      Lifestyle (HL) score (none/low, moderate and high adherence to lifestyle
      recommendations). We observed a significant association between adherence to
      lifestyle recommendations, increase in EPCs and exercise capacity between T1 and
      T2 (Delta EPCs p for trend <0.05; DeltaWatt max p for trend=0.004). In a
      multivariate logistic regression analyses, being in the highest tertile of HL
      score affected the likelihood of an increase of EPC levels at T2 [OR (95%
      confidence interval): 3.36 (1.0-10.72) p=0.04]. In conclusion, adherence to
      lifestyle recommendations provided during a CR program positively influences EPC
      levels and exercise capacity. 

PMID- 24573348
TI  - Inhibitory effects of Pericarpium zanthoxyli extract on adipocyte
      differentiation.
AB  - Obesity is a risk factor associated with numerous disorders, such as type 2
      diabetes, hypertension, dyslipidemia and coronary heart disease. In this study,
      we investigated the inhibitory effects of Pericarpium zanthoxyli extract (PZE) on
      the adipocytic differentiation of OP9 cells. During adipocyte differentiation,
      the OP9 cells were treated with 0, 10 and 20 ug/ml of PZE at various time
      intervals, followed by the examination of lipid droplet formation and the mRNA
      expression of adipogenesis-related genes. The cells treated with PZE during the
      early period (days 0-2) showed a significant reduction in the accumulation of
      lipid droplets, which were induced by a standard adipogenic cocktail, as well as
      a decrease in the expression of the adipogenesis-related transcription factor,
      peroxisome proliferator-activated receptor gamma (PPARgamma) and PPARgamma-target
      genes, such as adipocyte protein 2 (aP2), fatty acid synthase (FAS) and other
      adipocyte markers. Adipocyte differentiation was not inhibited by treatment with
      PZE during the late stage of differentiation (days 3-5). Thus, the inhibitory
      effects of PZE on adipocyte differentiation occurred during the early stages of
      adipogenesis, which was confirmed by the decrease in the levels of CCAAT/enhancer
      binding protein beta (C/EBPbeta) in a dose-dependent manner when the OP9 cells
      were exposed to PZE. Taken together, our results indicate that PZE inhibit the
      early stages of adipogenic differentiation by inhibiting C/EBPbeta expression.

PMID- 24573349
TI  - Clinical usefulness, angiographic characteristics, and safety evaluation of
      intracoronary acetylcholine provocation testing among 921 consecutive white
      patients with unobstructed coronary arteries.
AB  - BACKGROUND: Coronary spasm can cause myocardial ischemia and angina in patients
      with and those without obstructive coronary artery disease. However, provocation
      tests using intracoronary acetylcholine administration are rarely performed in
      clinical routine in the United States and Europe. Thus, we assessed the clinical
      usefulness, angiographic characteristics, and safety of intracoronary
      acetylcholine provocation testing in white patients with unobstructed coronary
      arteries. METHODS AND RESULTS: From September 2007 to June 2010, a total of 921
      consecutive patients (362 men, mean age 62+/-12years) who underwent diagnostic
      angiography for suspected myocardial ischemia and were found to have unobstructed
      coronary arteries (no stenosis >=50%) were enrolled. The intracoronary
      acetylcholine provocation testing was performed directly after angiography
      according to a standardized protocol. Three hundred forty-six patients (35%)
      reported chest pain at rest, 222 (22%) reported chest pain on exertion, 238 (24%)
      reported a combination of effort and resting chest pain, and 41 (4%) presented
      with troponin-positive acute coronary syndrome. The overall frequency of
      epicardial spasm (>75% diameter reduction with angina and ischemic ECG shifts)
      was 33.4%, and the overall frequency of microvascular spasm (angina and ischemic
      ECG shifts without epicardial spasm) was 24.2%. Epicardial spasm was most often
      diffuse and located in the distal coronary segments (P<0.01). No fatal or
      irreversible nonfatal complications occurred. However, 9 patients (1%) had minor
      complications (nonsustained ventricular tachycardia [n=1], fast paroxysmal atrial
      fibrillation [n=1], symptomatic bradycardia [n=6], and catheter-induced spasm
      [n=1]). CONCLUSIONS: Epicardial and microvascular spasm are frequently found in
      white patients with unobstructed coronary arteries. Epicardial spasm is most
      often diffuse and located in the distal coronary segments. The intracoronary
      acetylcholine provocation test is a safe technique to assess coronary vasomotor
      function.

PMID- 24573350
TI  - Coronary artery spasm as a cause of angina.

PMID- 24573351
TI  - The global burden of ischemic heart disease in 1990 and 2010: the Global Burden
      of Disease 2010 study.
AB  - BACKGROUND: Ischemic heart disease (IHD) burden consists of years of life lost
      from IHD deaths and years of disability lived with 3 nonfatal IHD sequelae:
      nonfatal acute myocardial infarction, angina pectoris, and ischemic heart
      failure. Our aim was to estimate the global and regional burden of IHD in 1990
      and 2010. METHODS AND RESULTS: Global and regional estimates of acute myocardial
      infarction incidence and angina and heart failure prevalence by age, sex, and
      world region in 1990 and 2010 were estimated based on data from a systematic
      review and nonlinear mixed-effects meta-regression methods. Age-standardized
      acute myocardial infarction incidence and angina prevalence decreased globally
      between 1990 and 2010; ischemic heart failure prevalence increased slightly. The
      global burden of IHD increased by 29 million disability-adjusted life-years (29%
      increase) between 1990 and 2010. About 32.4% of the growth in global IHD
      disability-adjusted life-years between 1990 and 2010 was attributable to aging of
      the world population, 22.1% was attributable to population growth, and total
      disability-adjusted life-years were attenuated by a 25.3% decrease in per capita
      IHD burden (decreased rate). The number of people living with nonfatal IHD
      increased more than the number of IHD deaths since 1990, but >90% of IHD
      disability-adjusted life-years in 2010 were attributable to IHD deaths.
      CONCLUSIONS: Globally, age-standardized acute myocardial infarction incidence and
      angina prevalence have decreased, and ischemic heart failure prevalence has
      increased since 1990. Despite decreased age-standardized fatal and nonfatal IHD
      in most regions since 1990, population growth and aging led to a higher global
      burden of IHD in 2010.

PMID- 24573353
TI  - Documenting the global burden of cardiovascular disease: a major achievement but
      still a work in progress.

PMID- 24573352
TI  - Temporal trends in ischemic heart disease mortality in 21 world regions, 1980 to
      2010: the Global Burden of Disease 2010 study.
AB  - BACKGROUND: Ischemic heart disease (IHD) is the leading cause of death worldwide.
      The Global Burden of Diseases, Risk Factors and Injuries 2010 Study estimated
      global and regional IHD mortality from 1980 to 2010. METHODS AND RESULTS: Sources
      for IHD mortality estimates were country-level surveillance, verbal autopsy, and
      vital registration data. Regional income, metabolic and nutritional risk factors,
      and other covariates were estimated from surveys and a systematic review. An
      estimation and validation process led to an ensemble model of IHD mortality for
      21 world regions. Globally, age-standardized IHD mortality has declined since the
      1980s, and high-income regions (especially Australasia, Western Europe, and North
      America) experienced the most remarkable declines. Age-standardized IHD mortality
      increased in former Soviet Union countries and South Asia in the 1990s and
      attenuated after 2000. In 2010, Eastern Europe and Central Asia had the highest
      age-standardized IHD mortality rates. More IHD deaths occurred in South Asia in
      2010 than in any other region. On average, IHD deaths in South Asia, North Africa
      and the Middle East, and sub-Saharan Africa occurred at younger ages in
      comparison with most other regions. CONCLUSIONS: In most world regions,
      particularly in high-income regions, age-standardized IHD mortality rates have
      declined significantly since 1980. High age-standardized IHD mortality in Eastern
      Europe, Central Asia, and South Asia point to the need to prevent and control
      established risk factors in those regions and to research the unique behavioral
      and environmental determinants of higher IHD mortality.

PMID- 24573355
TI  - Engineering interface structures and thermal stabilities via SPD processing in
      bulk nanostructured metals.
AB  - Nanostructured metals achieve extraordinary strength but suffer from low thermal
      stability, both a consequence of a high fraction of interfaces. Overcoming this
      tradeoff relies on making the interfaces themselves thermally stable. Here we
      show that the atomic structures of bi-metal interfaces in macroscale
      nanomaterials suitable for engineering structures can be significantly altered
      via changing the severe plastic deformation (SPD) processing pathway. Two types
      of interfaces are formed, both exhibiting a regular atomic structure and
      providing for excellent thermal stability, up to more than half the melting
      temperature of one of the constituents. Most importantly, the thermal stability
      of one is found to be significantly better than the other, indicating the
      exciting potential to control and optimize macroscale robustness via atomic-scale
      bimetal interface tuning. Taken together, these results demonstrate an innovative
      way to engineer pristine bimetal interfaces for a new class of simultaneously
      strong and thermally stable materials. 

PMID- 24573354
TI  - MicroRNA-10b promotes migration and invasion through KLF4 and HOXD10 in human
      bladder cancer.
AB  - The present study was performed to investigate the effect of microRNA-10b (miR
      10b) on cell migration and invasion in human bladder cancer (BC). Real-time PCR
      was performed to detect the expression of miR-10b in BC cell lines. miR-10b
      mimics, the negative control for mimics, miR-10b inhibitor and the negative
      control for inhibitor were transfected into BC cell lines and the effects of miR
      10b on the migration and invasion of cells were investigated through Transwell
      assay. Meanwhile, protein levels of KLF4, HOXD10, E-cadherin and MMP14 were
      measured. Luciferase assays were also performed to validate KLF4 and HOXD10 as
      miR-10b targets. In vivo metastasis assay was performed to validate if miR-10b
      can promote BC cell line metastasis in vivo. miR-10b is significantly upregulated
      in BC cell lines and metastatic tissues. Increased miR-10b expression
      significantly enhanced BC cell migration and invasion, while decreased miR-10b
      expression reduced cell migration and invasion. In vivo metastasis assay
      demonstrated that overexpression of miR-10b markedly promoted BC metastasis.
      Moreover, KLF4 and HOXD10 were identified as direct targets of miR-10b in BC
      cells. Silencing of KLF4 or HOXD10 recapitulated the pro-metastatic function.
      Furthermore, we found that E-cadherin and MMP14 may be the downstream factors of
      KLF4 and HOXD10 in the suppression of BC metastasis by miR-10b. These data
      suggest that miR-10b may function as oncogenes in BC cells. Targeting these novel
      strategies, inhibition of miR-10b/KLF4/E-cadherin axis and miR-10b/HOXD10/MMP14
      axis may be helpful as a therapeutic approach to block BC cell metastasis.

PMID- 24573356
TI  - Food source affects the expression of vitellogenin and fecundity of a biological
      control agent, Neoseiulus cucumeris.
AB  - Neoseiulus cucumeris (Oudemans) (Acari: Phytoseiidae) is one of the most widely
      used and important biological control agents for thrips and other small pests
      worldwide. In the present study, we cloned two cDNAs of vitellogenins (Vgs, NcVg1
      and NcVg2) and analyzed the effect of food source on the expression of both Vgs
      and fecundity in female adults. NcVgs showed higher sequence similarity to Vgs
      from Parasitiformes. Both neighbor-joining and maximum likelihood methods for
      phylogenetic analysis of NcVgs yielded similar topologies and showed that the
      Parasitiformes except Haemaphysalis longicornis segregated into a single clade
      that was separated into two subclades including one of both Vgs from N.
      cucumeris. Both transcripts, NcVg1 and NcVg2 revealed similar trends during
      developmental periods and reached the maximum level at the pre-oviposition
      period. When fed with different food sources, both NcVg1 and NcVg2 of female
      adults demonstrated a significant difference (P < 0.05) during the pre
      oviposition period. Meanwhile, a positive correlation between the expression of
      Vgs and fecundity was observed. Therefore, the nutrients provided by the food
      sources affected fecundity resulting in differential expression of Vgs.
      Vitellogenin expression can be used as a molecular marker of fecundity of N.
      cucumeris.

PMID- 24573357
TI  - Patients' experience compared with physicians' recommendations for treating fecal
      incontinence: a qualitative approach.
AB  - INTRODUCTION AND HYPOTHESIS: Using qualitative methods, we compared physician
      recommended treatment options for fecal incontinence to patient knowledge of
      treatment options. Our hypothesis was that physician recommendations were not
      being communicated well to patients and that this impaired patients' ability to
      cope with fecal incontinence. METHODS: Cognitive interviews were conducted with
      physicians who routinely care for women with fecal incontinence. Physicians were
      asked to describe their typical nonsurgical treatment recommendations and
      counseling for fecal incontinence. Women with bothersome fecal incontinence were
      recruited to participate in focus groups and asked about personal experience with
      fecal incontinence symptoms and treatment options. For both physician interviews
      and patient focus groups, qualitative data analysis was performed using grounded
      theory methodology. RESULTS: Physicians identified several barriers patients face
      when seeking treatment: lack of physician interest toward fecal incontinence, and
      patient embarrassment in discussing fecal incontinence. Physicians universally
      recommended fiber and pelvic floor exercise; they felt the majority
      (approximately 70-80 %) of patients will improve with these therapies.
      Collectively, patients were able to identify all treatment recommendations given
      by physicians, although many had discovered these treatments through personal
      experience. Three concepts emerged regarding treatment options that physicians
      did not identify but that patients felt were important in their treatment: hope
      for improvement, personal effort to control symptoms, and encouragement to go on
      living life fully. CONCLUSIONS: Whereas physicians had treatment to offer women
      with fecal incontinence, women had already found the best treatments through
      personal research and effort. Women want to hear a message of hope and
      encouragement and perceive personal effort from providers.

PMID- 24573359
TI  - Adenoma malignum presenting as urinary incontinence.
AB  - Adenoma malignum is a rare malignancy of the cervix that often presents, as in
      this case, as urinary incontinence (UI). Due to this symptomatology, women with
      adenoma malignum are often referred to urogynecologists for investigation and
      management. Without a high degree of suspicion, the diagnosis is easy to overlook
      due to the atypical presentation for a gynecological malignancy and the
      deceptively benign histopathology. Adenoma malignum is highly malignant, and a
      late diagnosis is often fatal. An early diagnosis is therefore crucial for
      curative management, and the following paper provides a timely reminder of this
      rare but potentially devastating condition. 

PMID- 24573358
TI  - A randomized controlled trial comparing anatomical and functional outcome between
      vaginal colposuspension and transvaginal mesh.
AB  - INTRODUCTION AND HYPOTHESIS: Our aim was to compare anatomical and functional
      outcome between vaginal colposuspension and transvaginal mesh. METHODS: This was
      a prospective randomized controlled trial in a teaching hospital. Sixty-eight
      women with stage >=3 anterior vaginal wall prolapse according to the Pelvic Organ
      Prolapse Quantification (POP-Q) system were assessed, randomized, and analyzed.
      Patients were randomized to anterior colporrhaphy with vaginal colposuspension (n
      = 35) or transvaginal mesh (n = 33). Primary outcome was objective cure rate of
      the anterior vaginal wall, defined as POP-Q <=1 at 2 years. Secondary outcomes
      were functional results, quality-of-life (QoL) scores, mesh-related morbidity,
      and onset of urinary incontinence. RESULTS: The anatomical result for point Ba
      was significantly better at 2 years in the mesh group (-2.8 cm) than in the
      colposuspension group (-2.4 cm) (p = 0.02). Concerning POP-Q stages, the
      anatomical success rate at 2 years was 84.4 % for colposuspension and 100 % for
      mesh (p = 0.05). There were 5 anatomic recurrences (15.6 %) in the
      colposuspension group. The erosion rate was 6 % (n = 2). No significant
      difference was noted regarding minor complications. Analysis of QoL
      questionnaires showed overall improvement in both groups, with no significant
      difference between them. CONCLUSIONS: The vaginal colposuspension technique of
      anterior vaginal wall prolapse repair gave good anatomical and functional results
      at 2 years. Transobturator vaginal mesh gave better 2-year anatomical results
      than vaginal colposuspension, with overall improvement in QoL in both groups.

PMID- 24573360
TI  - Clinical and urodynamic evaluation of women referred with diabetes mellitus.
AB  - INTRODUCTION AND HYPOTHESIS: We investigated the impact of diabetes mellitus (DM)
      on female lower urinary tract dysfunction. METHODS: We prospectively collected
      data of 1,640 consecutive diabetic women from the inpatient departments and
      outpatient clinics of urology, endocrinology, geriatrics, and nephrology in
      primary, secondary, and tertiary referral hospitals, rural healthcare stations,
      and nursing homes in Dujiangyan, China. Clinical histories were taken on an
      individualized basis depending on patient presentation. Urodynamics were
      performed in the enrolled female diabetic patients after excluding other causes
      of lower urinary tract dysfunction. Data on lower urinary tract symptoms and
      urodynamic parameters were analyzed. RESULTS: Ninety-three percent of diabetic
      women complained of lower urinary tract symptoms, and 88 % had positive
      urodynamic findings. Sixty-three percent presented with storage symptoms, 918
      cases of which had detrusor overactivity, 787 impaired detrusor contractility,
      and 131 detrusor areflexia. Among the 918 patients with impaired detrusor
      contractility or detrusor areflexia, the mean first sensation of filling was
      238.1 ml, with a mean maximum cystometric capacity of 624 ml, mean maximum flow
      rate of 9.6 ml/s, mean detrusor pressure at maximum flow rate of 32.4 cmH2O, and
      mean postvoid residual of 323 ml. Thirty-eight of 131 patients with detrusor
      areflexia had impaired renal function on blood chemistry test, and massive
      bilateral ureterohydronephrosis and "Christmas-tree-shaped" bladder in
      videourodynamic studies. On the whole, 95 % diabetic women had diabetic
      cystopathy. CONCLUSIONS: DM alters voiding patterns significantly, causing
      various lower urinary tract symptoms in a significant proportion of diabetic
      women. Diabetic cystopathy is a progressive condition with a spectrum of clinical
      symptoms and urodynamic findings. The prevalence of diabetic cystopathy is very
      high in Dujiangyan, China.

PMID- 24573364
TI  - Prison and community outbreak of severe respiratory infection due to adenovirus
      type 14p1 in Tayside, UK.
AB  - BACKGROUND: This report describes the investigation and public health management
      of a community-based outbreak of severe adenovirus serotype 14p1 respiratory
      infection affecting the Tayside area during 2011. It is the first report of an
      adenovirus outbreak involving prisons. METHODS: An outbreak-based/incident
      management approach was carried out. Alerts were sent out to local doctors,
      general practitioners, prison healthcare staff and consultants so that cases
      could be identified prospectively. Sequencing of hexon, fibre and E1A regions of
      adenovirus were carried out to genotype the viruses. RESULTS: Fifteen cases were
      identified in total, including 13 confirmed cases and 2 possible cases. There
      were 3 deaths amongst the 13 confirmed cases, with a case fatality rate of 23%.
      Eight of the cases had a direct association with one of the two prisons in the
      area. CONCLUSIONS: We advise that surveillance measures for adenovirus infection
      and guidelines for the management of critically ill patients should be developed
      in order to identify outbreaks at an early stage and allow patients to receive
      appropriate treatment. Adenovirus infection should be borne in mind as a cause of
      severe pneumonia in closed settings such as prisons.

PMID- 24573365
TI  - Implementing the Alcohol, Smoking, Substance Involvement Screening Test and
      linked brief intervention service in primary care in Thailand.
AB  - BACKGROUND: This paper reports findings on the implementation, acceptability and
      uptake of the screening and brief intervention programme based on the Alcohol,
      Smoking and Substance Involvement Screening Test (ASSIST) to help decrease
      substance misuse in primary care in Thailand. METHODS: Action research involving
      selection of suitable study areas; obtaining support for its introduction and
      corporation at national and local levels; training and monitoring of healthcare
      providers; delivery of the ASSIST-BI (brief intervention) procedure and
      assessments of acceptability and uptake of the procedure by patients and staff.
      RESULTS: Between October 2011 and October 2012, 5931 patients (2.5% of all
      patients attending primary care units) were screened with the ASSIST. Of these,
      29.6 and 3.4% were in the moderate- and high-risk groups, respectively, and were
      offered BI or other treatment. The most popular substances used were tobacco and
      alcohol. Less than 1% screened positively for illicit substances. CONCLUSION: The
      ASSIST detected many substance users capable of benefiting from intervention. The
      programme was well received by patients and staff. The development of the project
      from conception to inclusion in Thailand's national public health strategy is
      described and suggested as a model for introducing similar procedures into
      developing countries.

PMID- 24573366
TI  - Trends in lipid profiles among South Korean adults: 2005, 2008 and 2010 Korea
      National Health and Nutrition Examination Survey.
AB  - BACKGROUND: This study aimed to investigate recent trends in the prevalence and
      parameters of dyslipidemia and rates of lipid-lowering medication use in Korean
      adults. Trends in lipid profiles in subjects with hypertension, diabetes or
      obesity were also studied. METHODS: Data from the Korea National Health and
      Nutrition Examination Survey in 2005, 2008 and 2010 were used in this study. A
      total of 17 009 subjects participated in this study. RESULTS: There was a
      declining trend in the prevalence of dyslipidemia and an increasing trend in the
      rates of use of lipid-lowering medication among Korean adults. In both men and
      women, the age-adjusted mean high-density lipoprotein cholesterol level linearly
      increased. There was a significantly decreasing trend in the age-adjusted mean
      triglycerides in women and age-adjusted mean lipid-related ratios in both sexes.
      The age-adjusted mean total cholesterol level showed a slightly increasing trend
      and the age-adjusted mean low-density lipoprotein cholesterol level was not
      changed in both sexes. These patterns persisted among subjects not taking lipid
      lowering medication. The favorable trends were also observed in subjects with
      hypertension, diabetes and obesity. CONCLUSIONS: Our study showed favorable
      trends in the prevalence of dyslipidemia and in several lipid profiles among
      Korean adults.

PMID- 24573368
TI  - A partial proteome reference map of the wine lactic acid bacterium Oenococcus
      oeni ATCC BAA-1163.
AB  - Oenococcus oeni is the main lactic acid bacterium that carries out the malolactic
      fermentation in virtually all red wines and in some white and sparkling wines.
      Oenococcus oeni possesses an array of metabolic activities that can modify the
      taste and aromatic properties of wine. There is, therefore, industrial interest
      in the proteins involved in these metabolic pathways and related transport
      systems of this bacterium. In this work, we report the characterization of the O.
      oeni ATCC BAA-1163 proteome. Total and membrane protein preparations from O. oeni
      were standardized and analysed by two-dimensional gel electrophoresis. Using
      tandem mass spectrometry, we identified 224 different spots corresponding to 152
      unique proteins, which have been classified by their putative function and
      subjected to bioinformatics analysis. 

PMID- 24573369
TI  - Developing cellular therapies for retinal degenerative diseases.
AB  - Biomedical advances in vision research have been greatly facilitated by the
      clinical accessibility of the visual system, its ease of experimental
      manipulation, and its ability to be functionally monitored in real time with
      noninvasive imaging techniques at the level of single cells and with quantitative
      end-point measures. A recent example is the development of stem cell-based
      therapies for degenerative eye diseases including AMD. Two phase I clinical
      trials using embryonic stem cell-derived RPE are already underway and several
      others using both pluripotent and multipotent adult stem cells are in earlier
      stages of development. These clinical trials will use a variety of cell types,
      including embryonic or induced pluripotent stem cell-derived RPE, bone marrow- or
      umbilical cord-derived mesenchymal stem cells, fetal neural or retinal progenitor
      cells, and adult RPE stem cells-derived RPE. Although quite distinct, these
      approaches, share common principles, concerns and issues across the clinical
      development pipeline. These considerations were a central part of the discussions
      at a recent National Eye Institute meeting on the development of cellular
      therapies for retinal degenerative disease. At this meeting, emphasis was placed
      on the general value of identifying and sharing information in the so-called
      "precompetitive space." The utility of this behavior was described in terms of
      how it could allow us to remove road blocks in the clinical development pipeline,
      and more efficiently and economically move stem cell-based therapies for retinal
      degenerative diseases toward the clinic. Many of the ocular stem cell approaches
      we discuss are also being used more broadly, for nonocular conditions and
      therefore the model we develop here, using the precompetitive space, should
      benefit the entire scientific community. 

PMID- 24573376
TI  - Cavity types and microclimate: implications for ecological, evolutionary, and
      conservation studies.
AB  - The abiotic conditions of the immediate environment of organisms are key factors
      for a better understanding of ecological and evolutionary processes. Yet,
      information in this regard is biased towards some habitat types, landscapes, and
      organisms. Here, we present a 2-year comparative study of the microclimatic
      properties (temperature, relative humidity, and their fluctuation) of three
      cavity types (nest boxes, cavities in bridges, and burrows in sandy cliffs) in an
      arid environment. We found marked and consistent months-long differences in
      microclimate among the three cavity types. Nest boxes were colder than the other
      cavity types, with temperature oscillations being an order of magnitude higher
      than in other cavity types. In contrast, microclimate was very stable in burrows
      and cavities in bridges, the former being generally warmer and drier than the
      latter. We also discuss the biological implications of microclimatic conditions
      and its variation in different cavity types by presenting two case studies,
      namely the temperature-humidity index and water vapor pressure during the
      hatching period of an endotherm and the chilling period during the diapause of an
      ectotherm ectoparasite. We stress the need for comparative studies of the same
      organisms subjected to different microclimates given the important ecological,
      evolutionary, and conservation implications. 

PMID- 24573380
TI  - Synthesis and photo-darkening/photo-brightening of blue emitting doped
      semiconductor nanocrystals.
AB  - By programming the synthetic reaction chemistry, stable blue emitting Cu(i) or
      Ag(i) doped Al(iii) co-doped ZnS (Al,Cu:ZnS or Al,Ag:ZnS) semiconductor
      nanocrystals are designed. Further, the photostability of the obtained intense
      blue-violet emission is studied, and the effects of doping/co-doping are
      correlated. Finally, it is revealed that the strong binding surface ligand 1
      dodecanethiol and Al(iii) co-doping play pivotal roles in achieving such stable
      blue emitting doped nanocrystals. 

PMID- 24573377
TI  - Anti-Mullerian hormone (AMH): a reliable biomarker of oocyte quality in IVF.
AB  - PURPOSE: To evaluate the impact of serum AMH levels on stimulated IVF
      implantation and clinical pregnancy rates. METHODS: * DESIGN: Retrospective study
      with multivariate analysis. * SETTING: Clinique ovo (Montreal University
      affiliated Center). * PATIENT(S): Six hundred and thirty seven patients
      undergoing a stimulated IVF protocol were included. Only non-polycystic ovary
      patients at their first IVF attempt were considered for the analysis. *
      INTERVENTION(S): None. * MAIN OUTCOME MEASURES(S): Implantation and ongoing
      pregnancy rates. RESULT(S): Cycle outcomes were analysed according to AMH
      percentiles based on the AMH normogram per patient's age of our infertile
      population. Multivariate analyses were done to adjust for potential confounding
      factors such as age, total exogenous FSH dosage and number of eggs retrieved.
      Compared to the reference population, a significant lower mean implantation rate
      (0.26 vs 0.45) was observed in patients under 35 years of age with AMH < 1 ng/ml.
      Women with AMH < 25th percentile had less chances of having an embryo
      transferred, lower chances of having an ongoing pregnancy per started IVF cycle
      and a lower embryo freezing rate compared to the reference population.
      CONCLUSION(S): Patients with AMH < 0.47 ng/ml should be advised before starting a
      stimulated IVF cycle of the poorer prognosis compared to our reference population
      independently of their age, total exogenous FSH dosage and number of eggs
      retrieved. Therefore, AMH could enable a more individualized number of embryo
      transfer policy based on oocyte quality.

PMID- 24573381
TI  - Transforming growth factor-beta1 in the microenvironment of ischemia reperfusion
      injured kidney enhances the chemotaxis of mesenchymal stem cells to stromal cell
      derived factor-1 through upregulation of surface chemokine (C-X-C motif) receptor
      4.
AB  - Acute renal failure is one of the most common complications observed in
      hospitals. Although extensive studies have been carried out to search for
      therapeutic treatments, no effective cure has been established. In recent years,
      stem cell therapy for tissue engineering and repair has become a key area of
      study. Bone marrow mesenchymal stem cells (MSCs) have been demonstrated to
      exhibit a reparative role in ischemia reperfusion-injured kidney tissue, and the
      stromal cell-derived factor-1 (SDF-1)/chemokine (C-X-C motif) receptor 4 (CXCR4)
      axis has been found to play an important role in the migration and homing of
      MSCs. In the present study, transforming growth factor-beta1 (TGF-beta1) in the
      homogenate of the acute ischemia reperfusion-injured renal tissue was found to
      markedly increase the CXCR4 surface expression of MSCs, which contributes to the
      migration of MSCs to SDF-1. Neutralization of TGF-beta1 inhibited the migration
      in an antibody concentration-dependent manner, through downregulation of CXCR4
      localized to the membrane. These observations suggest a potential mechanism for
      MSC migration to the kidney which may provide a possible therapeutic target for
      curing acute renal failure.

PMID- 24573382
TI  - Rubbing salt into wounded endothelium: sodium potentiates proatherogenic effects
      of TNF-alpha under non-uniform shear stress.
AB  - Increased consumption of sodium is a risk factor for hypertension and
      cardiovascular diseases. In vivo studies indicated that high dietary sodium may
      have a direct negative influence on endothelium. We investigated the effects of
      high sodium on the endothelial activation during early steps of atherogenesis.
      Endothelial cells (HUVECs) grown in a model of arterial bifurcations were exposed
      to shear stress in the presence of normal or high (+ 30 mmol/l) sodium. Adherent
      THP-1 cells, and the adhesion molecule expression were quantified. Sodium channel
      blockers, pathways' inhibitors, and siRNA against tonicity-responsive enhancer
      binding protein (TonEBP) were used to identify the mechanisms of sodium effects
      on endothelium. ApoE-deficient mice on low-fat diet received water containing
      normal or high salt (8% w/v) for four weeks, and the influence of dietary salt on
      inflammatory cell adhesion in the common carotid artery and carotid bifurcation
      was measured by intravital microscopy. In vitro, high sodium dramatically
      increased the endothelial responsiveness to tumour necrosis factor-alpha under
      non-uniform shear stress. Sodium-induced increase in monocytic cell adhesion was
      mediated by reactive oxygen species and the endothelial nitric oxygen synthase,
      and was sensitive to the knockdown of TonEBP. The results were subsequently
      confirmed in the ApoE-deficient mice. As compared with normal-salt group, high
      salt intake significantly enhanced the adhesion of circulating CD11b+ cells to
      carotid bifurcations, but not to the straight segment of common carotid artery.
      In conclusion, elevated sodium has a direct effect on endothelial activation
      under atherogenic shear stress in vitro and in vivo, and promotes the endothelial
      leukocyte interactions even in the absence of increased lipid concentrations. 

PMID- 24573383
TI  - MYD88 and beyond: novel opportunities for diagnosis, prognosis and treatment in
      Waldenstrom's Macroglobulinemia.
AB  - Waldenstrom's Macroglobulinemia (WM) is a rare disease of the elderly with a
      median age of 63-68 years at diagnosis. Despite recent progress in biological
      insights and therapeutics, WM remains clinically challenging to diagnose and is
      difficult to manage with significant morbidity and lack of established curative
      therapies. Recently, the use of whole-genome sequencing has helped to identify a
      highly recurrent somatic mutation, myeloid differentiation factor 88 [MYD88]
      L265P in WM. This has fueled major interest in the field and as newer evidence
      accumulates, it is clear that that discovery of MYD88 L265P mutation may
      represent an important breakthrough in understanding the pathogenesis of WM and
      lymphoproliferative disorders. Recent scientific work in this field has also
      guided the identification of new targets such as CXCR4 and PI3K-delta that may
      have major implications in the future treatment of WM. This review discusses the
      role of MYD88 L265P mutations as well as targets beyond MYD88 in the setting of
      pathogenesis and development of future rational therapeutic trials focusing on
      patients diagnosed with WM. 

PMID- 24573384
TI  - Novel activating STAT5B mutations as putative drivers of T-cell acute
      lymphoblastic leukemia.

PMID- 24573385
TI  - The prognostic relevance of flt3 and npm1 mutations on older patients treated
      intensively or non-intensively: a study of 1312 patients in the UK NCRI AML16
      trial.
AB  - Although the prognostic impact of mutations of FLT3 and NPM1 have been
      extensively studied in younger patients with acute myeloid leukaemia, less is
      known in older patients whether treated intensively or non-intensively, or in the
      context of existing prognostic scores. In 1312 patients 16 and 21%, respectively
      had an FLT3 and NPM1 mutation. An FLT3 mutation did not affect remission rate in
      intensively or non-intensively treated patients but was associated with an
      inferior survival. All patients with an NPM1c mutation had a significantly higher
      remission rate irrespective of treatment approach but survival was not improved,
      overall, or in any genotype except as in younger patients, in the FLT3 WT NPM1c
      mutant subgroup. When incorporated into an established multi-parameter prognostic
      risk score, the molecular information provided additional prognostic definition
      in 11% of patients. 

PMID- 24573386
TI  - Human podocytes perform polarized, caveolae-dependent albumin endocytosis.
AB  - The renal glomerulus forms a selective filtration barrier that allows the passage
      of water, ions, and small solutes into the urinary space while restricting the
      passage of cells and macromolecules. The three layers of the glomerular
      filtration barrier include the vascular endothelium, glomerular basement membrane
      (GBM), and podocyte epithelium. Podocytes are capable of internalizing albumin
      and are hypothesized to clear proteins that traverse the GBM. The present study
      followed the fate of FITC-labeled albumin to establish the mechanisms of albumin
      endocytosis and processing by podocytes. Confocal imaging and total internal
      reflection fluorescence microscopy of immortalized human podocytes showed FITC
      albumin endocytosis occurred preferentially across the basal membrane. Inhibition
      of clathrin-mediated endocytosis and caveolae-mediated endocytosis demonstrated
      that the majority of FITC-albumin entered podocytes through caveolae. Once
      internalized, FITC-albumin colocalized with EEA1 and LAMP1, endocytic markers,
      and with the neonatal Fc receptor, a marker for transcytosis. After preloading
      podocytes with FITC-albumin, the majority of loaded FITC-albumin was lost over
      the subsequent 60 min of incubation. A portion of the loss of albumin occurred
      via lysosomal degradation as pretreatment with leupeptin, a lysosomal protease
      inhibitor, partially inhibited the loss of FITC-albumin. Consistent with
      transcytosis of albumin, preloaded podocytes also progressively released FITC
      albumin into the extracellular media. These studies confirm the ability of
      podocytes to endocytose albumin and provide mechanistic insight into cellular
      mechanisms and fates of albumin handling in podocytes.

PMID- 24573387
TI  - Persistence of 1,25D-induced hypercalciuria in alendronate-treated genetic
      hypercalciuric stone-forming rats fed a low-calcium diet.
AB  - Genetic hypercalciuric stone-forming (GHS) rats demonstrate increased intestinal
      Ca absorption, increased bone resorption, and reduced renal tubular Ca
      reabsorption leading to hypercalciuria and all form kidney stones. GHS have
      increased vitamin D receptors (VDR) at these sites of Ca transport. Injection of
      1,25(OH)2D3 (1,25D) leads to a greater increase in urine (u)Ca in GHS than in
      control Sprague-Dawley (SD), possibly due to the additional VDR. In GHS the
      increased uCa persists on a low-Ca diet (LCD) suggesting enhanced bone
      resorption. We tested the hypothesis that LCD, coupled to inhibition of bone
      resorption by alendronate (alen), would eliminate the enhanced 1,25D-induced
      hypercalciuria in GHS. SD and GHS were fed LCD and half were injected daily with
      1,25D. After 8 days all were also given alen until euthanasia at day 16. At 8
      days, 1,25D increased uCa in SD and to a greater extent in GHS. At 16 days, alen
      eliminated the 1,25D-induced increase in uCa in SD. However, in GHS alen
      decreased, but did not eliminate, the 1,25D-induced hypercalciuria, suggesting
      maximal alen cannot completely prevent the 1,25D-induced bone resorption in GHS,
      perhaps due to increased VDR. There was no consistent effect on mRNA expression
      of renal transcellular or paracellular Ca transporters. Urine CaP and CaOx
      supersaturation (SS) increased with 1,25D alone in both SD and GHS. Alen
      eliminated the increase in CaP SS in SD but not in GHS. If these results are
      confirmed in humans with IH, the use of bisphosphonates, such as alen, may not
      prevent the decreased bone density observed in these patients.

PMID- 24573389
TI  - Activation of ERK1/2 by NADPH oxidase-originated reactive oxygen species mediates
      uric acid-induced mesangial cell proliferation.
AB  - Hyperuricemia is associated with kidney complications including
      glomerulosclerosis and mesangial cell (MC) proliferation by poorly understood
      mechanisms. The present study investigated the underlying mechanisms that mediate
      uric acid (UA)-induced MC proliferation. A rat MC line, HBZY-1, was treated with
      various concentrations of UA in the presence or absence of a specific
      extracellular-regulated protein kinase 1/2 (ERK1/2) inhibitor (U0126), apocynin.
      UA dose dependently stimulated MC proliferation as shown by increased DNA
      synthesis and number of cells in the S and G2 phases in parallel with the
      upregulation of cyclin A2 and cyclin D1. In addition, UA time dependently
      promoted MC proliferation and significantly increased phosphorylation of ERK1/2
      but not c-Jun NH2-terminal kinase and p38 MAPK in MCs as assessed by
      immunoblotting. Inhibition of ERK1/2 signaling via U0126 markedly blocked UA
      induced MC proliferation. More importantly, UA induced intracellular reactive
      oxygen species (ROS) production of MCs dose dependently, which was completely
      blocked by apocynin, a specific NADPH oxidase inhibitor. Toll-like receptor
      (TLR)2 and TLR4 signaling had no effect on NADPH-derived ROS and UA-induced MC
      proliferation. Interestingly, pretreatment with apocynin inhibited ERK1/2
      activation, the upregulation of cyclin A2 and cyclin D1, and MC proliferation. In
      conclusion, UA-induced MC proliferation was mediated by NADPH/ROS/ERK1/2
      signaling pathway. This novel finding not only reveals the mechanism of UA
      induced MC cell proliferation but also provides some potential targets for future
      treatment of UA-related glomerular injury. 

PMID- 24573388
TI  - Increasing cGMP-dependent protein kinase activity attenuates unilateral ureteral
      obstruction-induced renal fibrosis.
AB  - Our previous studies support the protective effect of cGMP and cGMP-dependent
      protein kinase I (PKG-I) pathway on the development of renal fibrosis. Therefore,
      in the present studies, we determined whether pharmacologically or genetically
      increased PKG activity attenuates renal fibrosis in a unilateral ureteral
      obstruction (UUO) model and also examined the mechanisms involved. To increase
      PKG activity, we used the phosphodiesterase 5 inhibitor sildenafil and PKG
      transgenic mice. UUO model was induced in wild-type or PKG-I transgenic mice by
      ligating the left lateral ureteral and the renal fibrosis was observed after 14
      days of ligation. Sildenafil was administered into wild-type UUO mice for 14
      days. In vitro, macrophage and proximal tubular cell function was also analyzed.
      We found that sildenafil treatment or PKG transgenic mice had significantly
      reduced UUO-induced renal fibrosis, which was associated with reduced TGF-beta
      signaling and reduced macrophage infiltration into kidney interstitial. In vitro
      data further demonstrated that both macrophages and proximal tubular cells were
      important sources of UUO-induced renal TGF-beta levels. The interaction between
      macrophages and tubular cells contributes to TGF-beta-induced renal fibrosis.
      Taken together, these data suggest that increasing PKG activity ameliorates renal
      fibrosis in part through regulation of macrophage and tubular cell function,
      leading to reduced TGF-beta-induced fibrosis.

PMID- 24573392
TI  - Renal tubular Notch signaling triggers a prosenescent state after acute kidney
      injury.
AB  - The aging kidney has a diminished regenerative potential and an increased
      tendency to develop tubular atrophy and fibrosis after acute injury. In this
      study, we found that activation of tubular epithelial Notch1 signaling was
      prolonged in the aging kidney after ischemia/reperfusion (IR) damage. To analyze
      the consequences of sustained Notch activation, we generated mice with
      conditional inducible expression of Notch1 intracellular domain (NICD) in
      proximal tubules. NICD kidneys were analyzed 1 and 4 wk after renal IR.
      Conditional NICD expression was associated with aggravated tubular damage, a
      fibrotic phenotype, and the expression of cellular senescence markers p21 and
      p16(INK4a). In wild-type mice pharmacological inhibition of Notch using the gamma
      secretase inhibitor N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t
      butyl ester (DAPT) improved tubulo-interstitial damage and antagonized the
      prosenescent pathway activation after IR. In vitro, activation of Notch signaling
      with delta-like-ligand-4 caused prosenescent changes in tubular cells while
      inhibition with DAPT attenuated these changes. In conclusion, our data suggest
      that sustained epithelial Notch activation after IR might contribute to the
      inferior outcome of old kidneys after injury. Sustained epithelial activation of
      Notch is associated with a prosenescent phenotype and maladaptive repair. 

PMID- 24573390
TI  - Novel MAPK-dependent and -independent tubulogenes identified via microarray
      analysis of 3D-cultured Madin-Darby canine kidney cells.
AB  - Cystogenesis and tubulogenesis are basic building blocks for many epithelial
      organs, including the kidney. Most researchers have used two-dimensional (2D)
      cell culture to investigate signaling pathways downstream of hepatocyte growth
      factor (HGF). We hypothesize that three-dimensional (3D) collagen-grown Madin
      Darby canine kidney (MDCK) cells, which form cysts and then tubulate in response
      to HGF, are a much more in vivo-like system for the identification of novel
      tubulogenes. With the use of a canine microarray containing over 20,000 genes,
      2,417 genes were identified as potential tubulogenes that were differentially
      regulated, exclusively in 3D-grown MDCK cells. Among these, 840 were dependent on
      MAPK signaling. Importantly, this work shows that many putative tubulogenes,
      previously identified via microarray analysis of 2D cultures, including by us, do
      not change in 3D culture and vice versa. The use of a 3D-culture system allowed
      for the identification of novel MAPK-dependent and -independent genes that
      regulate early renal tubulogenesis in vitro, e.g., matrix metalloproteinase 1
      (MMP1). Knockdown of MMP1 led to defects in cystogenesis and tubulogenesis in 3D
      grown MDCK cells, most likely due to problems establishing normal polarity. We
      suggest that data obtained from 2D cultures, even those using MDCK cells treated
      with HGF, should not be automatically extrapolated to factors important for
      cystogenesis and tubulogenesis. Instead, 3D culture, which more closely
      replicates the biological environment and is therefore a more accurate model for
      identifying tubulogenes, is preferred. Results from the present analysis will be
      used to build a more accurate model of the signaling pathways that control
      cystogenesis and tubulogenesis.

PMID- 24573395
TI  - Diabetic retinopathy and renal function in Chinese type 2 diabetic patients.
AB  - AIMS: To evaluate associations of diabetic retinopathy (DR) with renal function
      in Chinese type 2 diabetic patients. METHODS: This cross-sectional study enrolled
      523 type 2 diabetic patients. All patients underwent ophthalmic examination to
      assess DR [normal, non-proliferative DR (NPDR), proliferative DR (PDR)]. The
      renal function measurements were taken in urine and blood. The estimated
      glomerular rate (eGFR) and albumin/creatinine ratio (ACR) were calculated using
      standard formulas. The chronic kidney disease (CKD) was defined as eGFR < 60
      mL/min/1.73 m(2), and microalbuminuria was defined as ACR > 17 for males and ACR
      > 25 for females. The associations of DR with renal function and CKD were
      assessed by regression models, without and with the adjustment of risk factors
      for CKD. RESULTS: In multivariate analysis, increasing severity of DR was
      significantly associated with lower eGFR (p < 0.001), higher level of retinol
      binding protein (p < 0.001), and larger ACR (p < 0.0001). The DR was
      significantly associated increased risk of CKD with odds ratio of 2.22 (95% CI
      1.01-4.86) for NPDR and 3.52 (1.30-9.55) for PDR. CONCLUSIONS: Among Chinese type
      2 diabetic patients, increasing DR severity is significantly associated reduced
      kidney function and increased risk of CKD. These associations are independent of
      risk factors for CKD, suggesting that assessment of DR may provide useful
      information on the renal function and risk of kidney disease.

PMID- 24573397
TI  - Minority stress in lesbian, gay, and bisexual young adults in Australia:
      associations with psychological distress, suicidality, and substance use.
AB  - Lesbian, gay, bisexual, and other same-sex attracted young people have been shown
      to be at a higher risk of mental health problems, including depression, anxiety,
      suicidality, and substance abuse, compared to their heterosexual peers.
      Homophobic prejudice and stigma are often thought to underlie these disparities.
      In this study, the relationship between such experiences of social derogation and
      mental health and substance use in same-sex attracted young people was examined
      using Meyer's minority stress theory. An online survey recruited 254 young women
      and 318 young men who identified as same-sex attracted, were aged 18-25 years,
      and lived in Sydney, Australia. Multivariate logistic regression analyses showed
      that internalized homophobia, perceived stigma, and experienced homophobic
      physical abuse were associated with higher levels of psychological distress and
      self-reported suicidal thoughts in the previous month. Furthermore, perceived
      stigma and homophobic physical abuse were associated with reporting a lifetime
      suicide attempt. The association between minority stress and substance use was
      inconsistent. While, as expected, higher levels of perceived stigma were
      associated with club drug dependence, there was an inverse association between
      internalized homophobia and club drug use, and between perceived stigma and
      hazardous alcohol use. The findings of this study provide support for the
      minority stress theory proposition that chronic social stress due to sexual
      orientation is associated with poorer mental health. The high rates of mental
      health and substance use problems in the current study suggest that same-sex
      attracted young people should continue to be a priority population for mental
      health and substance use intervention and prevention.

PMID- 24573398
TI  - Childhood sexual abuse and HIV-related risks among men who have sex with men in
      Washington, DC.
AB  - Childhood sexual abuse (CSA) has been reported to be disproportionately higher
      among men who have sex with men (MSM) than among heterosexual men; it has also
      been found to be significantly positively associated with HIV status and HIV risk
      factors, including unprotected anal intercourse. The purpose of this study was to
      assess the correlates of CSA in a sample of community-recruited MSM, investigate
      race as a potential effect modifier, and describe the independent association
      between CSA and HIV infection in Washington, DC. A total of 500 MSM were
      recruited by venue-based sampling in 2008 as part of the National HIV Behavioral
      Surveillance. More than one-half of MSM identified as White, while one-third
      identified as Black. CSA was reported by 17.5 % of the 451 MSM, with the first
      instance of abuse occurring at a median age of 8.3 (interquartile range = 5.0,
      11.0). In multivariable analysis, HIV-positive men were significantly more likely
      to report a history of CSA compared to HIV-negative men after adjusting for
      intimate partner violence in the last 12 months, having been arrested in the last
      12 months, and depressive symptoms. HIV-positive MSM had more than four times the
      odds of reporting CSA after controlling for other correlates (aOR = 4.19; 95 % CI
      2.26, 7.75). Despite hypothesizing that race modified the effect of CSA on HIV
      infection we found this was not the case in this sample. More research is needed
      to investigate the potential pathway between a history of CSA and HIV infection,
      and how this contributes to driving the HIV epidemic among MSM in Washington, DC.

PMID- 24573399
TI  - Explaining the suicide risk of sexual minority individuals by contrasting the
      minority stress model with suicide models.
AB  - Many studies have found elevated levels of suicide ideation and attempts among
      sexual minority (homosexual and bisexual) individuals as compared to heterosexual
      individuals. The suicide risk difference has mainly been explained by minority
      stress models (MSTM), but the application of established suicidological models
      and testing their interrelations with the MSTM has been lacking so far.
      Therefore, we have contrasted two established models explaining suicide risk, the
      Interpersonal Psychological Theory (IPT) (Joiner, 2005) and the Clinical Model
      (CM) (Mann et al., 1999), with the MSTM (Meyer, 2003) in a Bavarian online-sample
      of 255 adult sexual minority participants and 183 heterosexual participants. The
      results suggested that the CM and the IPT model can well explain suicide ideation
      among sexual minorities according to the factors depression, hopelessness,
      perceived burdensomeness, and failed belongingness. The CM and the IPT were
      intertwined with the MSTM via internalized homophobia, social support, and early
      age of coming out. Early coming out was associated with an increased suicide
      attempt risk, perhaps through violent experiences that enhanced the capability
      for suicide; however, coming out likely changed to a protective factor for
      suicide ideation by enhanced social support and reduced internalized homophobia.
      These results give more insight into the development of suicide risk among sexual
      minority individuals and may be helpful to tailor minority-specific suicide
      prevention strategies. 

PMID- 24573394
TI  - Lipid, blood pressure and kidney update 2013.
AB  - The year 2013 proved to be very exciting as far as landmark trials and new
      guidelines in the field of lipid disorders, blood pressure and kidney diseases.
      Among these are the International Atherosclerosis Society Global Recommendations
      for the Management of Dyslipidemia, European Society of Cardiology (ESC)/European
      Society of Hypertension Guidelines for the Management of Arterial Hypertension,
      American Diabetes Association Clinical Practice Recommendations, the Kidney
      Disease: Improving Global Outcomes Clinical Practice Guidelines for Managing
      Dyslipidemias in Chronic Kidney Disease (CKD) Patients, the American College of
      Cardiology/American Heart Association Guideline on the Treatment of Blood
      Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults, the Joint
      National Committee Expert Panel (JNC 8) Evidence-Based Guideline for the
      Management of High Blood Pressure in Adults, the American Society of
      Hypertension/International Society of Hypertension Clinical Practice Guidelines
      for the Management of Hypertension in the Community, the American College of
      Physicians Clinical Practice Guideline on Screening, Monitoring, and Treatment of
      Stage 1-3 CKD and many important trials presented among others during the ESC
      Annual Congress in Amsterdam and the American Society of Nephrology Annual
      Meeting--Kidney Week in Atlanta, GA. The paper is an attempt to summarize the
      most important events and reports in the mentioned areas in the passing year.

PMID- 24573400
TI  - Novel cancer-testis antigen expression on glioma cell lines derived from high
      grade glioma patients.
AB  - Glioblastoma multiforme (GBM) is one of the most malignant and aggressive tumors,
      and has a very poor prognosis with a mean survival time of <2 years, despite
      intensive treatment using chemo-radiation. Therefore, novel therapeutic
      approaches including immunotherapy have been developed against GBM. For the
      purpose of identifying novel target antigens contributing to GBM treatment, we
      developed 17 primary glioma cell lines derived from high-grade glioma patients,
      and analyzed the expression of various tumor antigens and glioma-associated
      markers using a quantitative PCR and immunohistochemistry (IHC). A quantitative
      PCR using 54 cancer-testis (CT) antigen-specific primers showed that 36 CT
      antigens were positive in at least 1 of 17 serum-derived cell lines, and 17
      antigens were positive in >50% cell lines. Impressively, 6 genes (BAGE, MAGE-A12,
      CASC5, CTAGE1, DDX43 and IL-13RA2) were detected in all cell lines. The
      expression of other 13 glioma-associated antigens than CT genes were also
      investigated, and 10 genes were detected in >70% cell lines. The expression of CT
      antigen and glioma-associated antigen genes with a high frequency were also
      verified in IHC analysis. Moreover, a relationship of antigen gene expressions
      with a high frequency to overall survival was investigated using the Repository
      of Molecular Brain Neoplasia Data (REMBRANDT) database of the National Cancer
      Institute, and expression of 6 genes including IL-13RA2 was inversely correlated
      to overall survival time. Furthermore, 4 genes including DDX43, TDRD1, HER2 and
      gp100 were identified as MGMT-relevant factors. In the present study, several CT
      antigen including novel genes were detected in high-grade glioma primary cell
      lines, which might contribute to developing novel immunotherapy and glioma
      specific biomarkers in future. 

PMID- 24573401
TI  - The biomaterial-mediated healing of critical size bone defects in the
      ovariectomized rat.
AB  - This study demonstrated an impaired biomaterial-mediated bone regeneration in a
      critical sized calvarial defect established within an ovariectomized rat model.
      Histological and microtomographic evidences were supported by an impaired
      osteoblastic gene expression and altered expression of estrogen receptors and
      adipogenic markers. INTRODUCTION: This work aims to address the bone regeneration
      process in the ovariectomized rat model, by assessing a calvarial critical size
      defect implanted with a biocompatible bovine bone mineral graft. METHODS: Animals
      were randomly divided into two groups: Ovx (bilateral ovariectomy) and Sham
      (control surgery). Following 8 weeks, all animals were submitted to a surgical
      bicortical craniotomy (5-mm circular critical size defect), which was filled with
      a biocompatible mineral graft. Animals were euthanized at 1, 3, and 6 months
      following graft implantation (n = 10), and results on the orthotopic bone
      regeneration process were blindly evaluated by radiographic, microtomographic,
      histological, histomorphometric, and gene expression techniques. RESULTS: In the
      attained model, in both Sham and Ovx groups, the bone regenerative process was
      found to occur in a slow-paced manner. Likewise, a qualitative evaluation of the
      microtomographic and histological analysis, as well as quantitative data from
      histomorphometric indexes, revealed reduced bone regeneration in Ovx animals, at
      the assayed time points. Significant differences were attained at the 3 and 6
      months. Gene expression analysis revealed a reduced expression of osteoblastic
      related genes and an altered expression of estrogen receptors and adipogenic
      markers, within the regenerating bone of Ovx animals. CONCLUSIONS: Due to the
      similarities between the osteoporotic animal model and the human condition of
      postmenopausal osteoporosis, it might be relevant to consider the potential
      clinical implication of the osteoporotic condition in the biomaterial-mediated
      bone tissue healing/regeneration process.

PMID- 24573402
TI  - Identification of differentially expressed microRNAs in metastatic melanoma using
      next-generation sequencing technology.
AB  - In this study, we investigated differentially expressed microRNAs (miRNAs or
      miRs) and their functions in metastatic melanoma using next-generation sequencing
      technology. The GSE36236 data set was downloaded from the Gene Expression Omnibus
      (GEO) database and 4 primary cutaneous melanoma samples (used as controls) and 3
      metastatic melanoma samples were selected from 31 samples for further analysis.
      Firstly, the differentially expressed miRNAs were screened by limma package in R
      language. Secondly, the target genes of the miRNAs were retrieved with
      TargetScanHuman 6.2, and the interactions among these genes were identified by
      String and an interaction network was established. Finally, functional and
      pathway analyses were performed for the genes in the network using Expression
      Analysis Systematic Explorer (EASE). A total of 4 differentially expressed miRNAs
      (hsa-miR-146, hsa-miR-27, hsa-miR-877 and hsa-miR-186) were obtained between the
      metastatic melanoma and primary cutaneous melanoma samples. We predicted 101 high
      confidence target genes of hsa-miR-27 and obtained a network with 41
      interactions. Finally, functional and pathway analyses revealed that the genes in
      the network were significantly enriched at the transcriptional level.
      Differentially expressed miRNAs were identified in the metastatic melanoma
      compared with the primary cutaneous melanoma samples and the target genes of hsa
      miR-27 were found to be significantly enriched at the transcriptional level. The
      results presented in our study may prove helpful in the diagnosis and treatment
      of metastatic melanoma.

PMID- 24573404
TI  - Establishment of successively transplantable rabbit VX2 cancer cells that express
      enhanced green fluorescent protein.
AB  - Morphological detection of cancer cells in the rabbit VX2 allograft
      transplantation model is often difficult in a certain region such as serosal
      cavity where reactive mesothelial cells mimic cancer cells and both cells share
      common markers such as cytokeratins. Therefore, tagging VX2 cells with a specific
      and sensitive marker that easily distinguishes them from other cells would be
      advantageous. Thus, we tried to establish a successively transplantable, enhanced
      green fluorescent protein (EGFP)-expressing VX2 model. Cancer cells obtained from
      a conventional VX2-bearing rabbit were cultured in vitro and transfected with an
      EGFP-encoding vector, and then successively transplanted in Healthy Japanese
      White rabbits (HJWRs) (n = 8). Besides, conventional VX2 cells were transplanted
      in other HJWRs (n = 8). Clinicopathological comparison analyses were performed
      between the two groups. The success rate of transplantation was 100% for both
      groups. The sensitivity and specificity of EGFP for immunohistochemical detection
      of VX2 cells were 84.3 and 100%, respectively. No significant differences in
      cancer cell morphology, tumor size (P = 0.742), Ki-67 labeling index (P = 0.878),
      or survival rate (P = 0.592) were observed between the two. VX2 cells can be
      genetically altered, visualized by EGFP, and successively transplanted without
      significant alteration of morphological and biological properties compared to
      those of the conventional model.

PMID- 24573405
TI  - Analysis of copper concentration in human serum by application of total
      reflection X-ray fluorescence method.
AB  - The chemotherapy and photon radiotherapy are the most often applied methods in
      treatment of the cancer diseases because of their effectiveness and high cure
      rates. Apart from eligible destruction of the tumour, one of the side effects of
      these treatment methods is possible modification of main and trace element
      concentration in different human tissues and fluids. In this paper, the copper
      (Cu) level in human serum was determined by total reflection X-ray fluorescence
      method in 142 chemotherapy patients and in 44 healthy persons being a control
      group. The Cu concentration in the chemotherapy group was found to be on the
      level 1.78 +/- 0.909 mg/L, while in the control group, it was 1.08 +/- 0.551
      mg/L. Performed measurements allowed for calculation of the parameters of copper
      concentration distribution (mean value, standard deviation, median) for both
      analysed groups. The theoretical nature of the concentration distribution was
      tested and found as a log-normal distribution (control group) and a log-stable
      distribution (chemotherapy group). The copper concentration distributions for
      both studied group were statistically compared using Kolmogorov-Smirnov test, and
      the conclusion was that the distributions are statistically different. Serum Cu
      levels were significantly higher in the chemotherapy group than in the control
      group. Taking into account the results for the control group, the copper
      concentration reference quantile ranges in human serum were obtained. The values
      of the mean, median and other quantiles determined in this case can be applied in
      two-group comparison studies. The obtained results can be used as a diagnostic
      tool for chemotherapy patients.

PMID- 24573406
TI  - Protective effects of selenium on cadmium-induced brain damage in chickens.
AB  - Selenium (Se) is an important dietary micronutrient with antioxidative roles.
      Cadmium (Cd), a ubiquitous environmental pollutant, is known to cause brain
      lesion in rats and humans. However, little is reported about the deleterious
      effects of subchronic Cd exposure on the brain of poultry and the protective
      roles on the brain by Se against Cd. The aim of this study was to investigate the
      protective effects of Se on Cd-induced brain damage in chickens. One hundred
      twenty 100-day-old chickens were randomly assigned to four groups and were fed a
      basal diet, or Se (as 10 mg Na2SeO3/kg dry weight of feed), Cd (as 150 mg
      CdCl2/kg dry weight of feed), or Cd + Se in their basic diets for 60 days. Then,
      concentrations of Cd and Se, production of nitric oxide (NO), messenger RNA
      (mRNA) level and activity of inducible NO synthase (iNOS), level of oxidative
      stress, and histological and ultrastructural changes of the cerebrum and
      cerebellum were examined. The results showed that Cd exposure significantly
      increased Cd accumulation, NO production, iNOS activities, iNOS mRNA level, and
      MDA content in the cerebrum and cerebellum. Cd treatment obviously decreased Se
      content and antioxidase activities and caused histopathological changes in the
      cerebrum and cerebellum. Se supplementation during dietary Cd obviously reduced
      Cd accumulation, NO production, mRNA level and activity of iNOS, oxidative
      stress, and histopathological damage in the cerebrum and cerebellum of chickens.
      It indicated that Se ameliorates Cd-induced brain damage in chickens by
      regulating iNOS-NO system changes, and oxidative stress induced by Cd and Se can
      serve as a potential therapeutic for Cd-induced brain lesion of chickens.

PMID- 24573411
TI  - Standardization of the methylation-specific PCR method for analyzing BRCA1 and ER
      methylation.
AB  - The significant differences in DNA methylation that are considered to be a
      biomarker for the diagnosis of cancer are a barrier to the application of
      biomarkers in the clinical field. In the present study, new primers were designed
      and further standard controls were set up to validate the accuracy of the
      methylation-specific PCR (MSP), a method widely used to analyze DNA methylation.
      By analyzing the methylation pattern of breast cancer 1 (BRCA1) and estrogen
      receptor (ER) in 60 patients with breast cancer, the number of cases of
      methylated BRCA1 and ER detected by the primer was 7/60 and 21/60, respectively,
      whereas that detected by the previous widely used primers was 25/60 and 47/60,
      respectively. Sequencing of the MSP products indicated that the 18 and 26 false
      positive methylations of BRCA1 and ER, respectively, were due to insufficient
      validation of the previously used primers. Thus, the present study proposes that
      all studies based on the MSP approach should incorporate more controls to
      validate the precision of the MSP primers.

PMID- 24573413
TI  - Long-term adherence to a 5 day antibiotic course guideline for treatment of
      intensive care unit (ICU)-associated Gram-negative infections.
AB  - OBJECTIVES: To determine long-term adherence to a 5 day antibiotic course
      guideline for treating intensive care unit (ICU)-acquired Gram-negative bacteria
      (GNB) infections. METHODS: Descriptive analysis of patient-level data on all GNB
      active antibiotics prescribed from day 3 and all GNB identified in clinical
      samples in 5350 patients admitted to a 30 bed general ICU between 2002 and 2009.
      RESULTS: Four thousand five hundred and eleven of 5350 (84%) patients were
      treated with one or more antibiotics active against GNB commenced from day 3.
      Gentamicin was the most frequently prescribed antibiotic (92.2 days of
      therapy/1000 patient-days). Only 6% of courses spanned >6 days of therapy and 89%
      of antibiotic therapy days were with a single antibiotic active against GNB.
      There was no significant difference between gentamicin and meropenem in the
      number of first courses in which a resistant GNB was identified in blood cultures
      [11/1177 (0.9%) versus 5/351 (1.4%); P = 0.43] or respiratory tract specimens
      [59/951 (6.2%) versus 17/246 (6.9%); P = 0.68] at the time of starting therapy.
      CONCLUSIONS: This study demonstrates long-term adherence to a 5 day course
      antibiotic guideline for treatment of ICU-associated GNB infections. This
      guideline is a potential antibiotic-sparing alternative to currently recommended
      dual empirical courses extending to >=7 days.

PMID- 24573412
TI  - Structure-guided optimization of small molecule c-Abl activators.
AB  - c-Abl kinase is maintained in its normal inactive state in the cell through an
      assembled, compact conformation. We describe two chemical series that bind to the
      myristoyl site of the c-Abl kinase domain and stimulate c-Abl activation. We
      hypothesize that these molecules activate c-Abl either by blocking the C-terminal
      helix from adopting a bent conformation that is critical for the formation of the
      autoinhibited conformation or by simply providing no stabilizing interactions to
      the bent conformation of this helix. Structure-based molecular modeling guided
      the optimization of binding and activation of c-Abl of these two chemical series
      and led to the discovery of c-Abl activators with nanomolar potency. The small
      molecule c-Abl activators reported herein could be used as molecular tools to
      investigate the biological functions of c-Abl and therapeutic implications of its
      activation. 

PMID- 24573414
TI  - Assembly-mediated interplay of dipolar interactions and surface spin disorder in
      colloidal maghemite nanoclusters.
AB  - Controlled assembly of single-crystal, colloidal maghemite nanoparticles is
      facilitated via a high-temperature polyol-based pathway. Structural
      characterization shows that size-tunable nanoclusters of 50 and 86 nm diameters
      (D), with high dispersibility in aqueous media, are composed of ~13 nm (d)
      crystallographically oriented nanoparticles. The interaction effects are examined
      against the increasing volume fraction, phi, of the inorganic magnetic phase that
      goes from individual colloidal nanoparticles (phi = 0.47) to clusters (phi =
      0.72). The frozen-liquid dispersions of the latter exhibit weak ferrimagnetic
      behaviour at 300 K. Comparative Mossbauer spectroscopic studies imply that intra
      cluster interactions come into play. New insight emerges from the clusters'
      temperature-dependent ac susceptibility that displays two maxima in chi''(T),
      with strong frequency dispersion. Scaling-law analysis together with the observed
      memory effects suggests that a superspin-glass state settles-in at TB ~ 160-200
      K, while at lower-temperatures, surface spin-glass freezing is established at Tf
      ~ 40-70 K. In such nanoparticle-assembled systems, with increased phi, Monte
      Carlo simulations corroborate the role of the inter-particle dipolar interactions
      and that of the constituent nanoparticles' surface spin disorder in the emerging
      spin-glass dynamics. 

PMID- 24573415
TI  - Evidence and clinical judgment: vena cava filters.

PMID- 24573418
TI  - Low expression of Mig-6 is associated with poor survival outcome in NSCLC and
      inhibits cell apoptosis via ERK-mediated upregulation of Bcl-2.
AB  - Mitogen-inducible gene-6 (Mig-6), an immediate early response gene, is a specific
      negative regulator of epidermal growth factor receptor (EGFR). Ablation of Mig-6
      has been shown to induce tumor formation in various tissues, supporting the tumor
      suppressor function of Mig-6. However, little is known about the role of Mig-6 in
      non-small cell lung cancer (NSCLC) apoptosis, nor has the contribution of
      upregulated Mig-6 on biological behaviors of A549 and H157 cells previously been
      reported. The aim of the present study was to investigate the effects of
      exogenously transfected Mig-6 on proliferation, invasion and apoptosis of A549
      and H157 cells and to identify novel underlying mechanisms of Mig-6-induced
      apoptosis. We used immunohistochemical staining to examine the expression of Mig
      6 protein in NSCLC tissues. For evaluation of the prognostic value of Mig-6
      expression to each clinicopathologic factor, Kaplan-Meier method and Cox's
      proportional hazards model were employed. Mig-6 low expression was correlated
      with a poor prognosis in patients with lung cancer. Patients with high expression
      of Mig-6 had a statistically significantly longer survival than those with low
      expression of Mig-6. Cox's regression analysis indicated that loss of Mig-6
      expression was an independent, unfavorable prognostic factors. We utilized siRNA
      targeting Mig-6 and Mig-6 overexpression plasmid to determine the effect of Mig-6
      on lung cancer cells. Flow cytometry studies revealed Mig-6 overexpression
      promoted apoptosis in NSCLC cell lines. siRNA-mediated Mig-6 knockdown inhibited
      apoptosis of cancer cells, but this anti-apoptotic effect was abolished by
      inhibition of ERK. Upregulation of Mig-6 decreased the proliferation and invasive
      potential of transfected cells. Moreover, upregulation of Mig-6 inhibited
      proliferation and invasion of A549 and H157 cells. Collectively, our results
      showed that Mig-6 is a potential biomarker for evaluation of tumor prognosis of
      lung cancer. Mig-6 promotes apoptosis in lung cancer cells via the ERK pathway. 

PMID- 24573416
TI  - Inhibition of angiotensin-converting enzyme by aqueous extract of tomato.
AB  - PURPOSE: To investigate the presence of anti-angiotensin converting enzyme (ACE)
      factors in aqueous extract of tomato. METHODS: The bio-guided fractionation of
      the aqueous extract of tomato produced a sugar-free, heat-stable fraction with
      molecular mass <1,000 Da from tomatoes. The sugar-free tomato extract (TE) was
      tested for its anti-ACE activity using human plasma and rabbit lung pure ACE. In
      addition, its effect on human platelet aggregation induced by ADP, collagen or
      arachidonic acid was determined. The mechanism of platelet inhibitory action of
      TE was investigated by measuring platelet factor 4 (PF4) release and cAMP
      synthesis by platelets. RESULTS: Typically, 100 g tomatoes produced 72.2 +/- 4.7
      mg of TE. This extract inhibited both platelet aggregation and plasma ACE
      activity in a dose-dependent manner. It inhibited platelet aggregation in
      response to ADP, collagen or arachidonic acid, and inhibitory action was mediated
      in part by reducing platelet PF4 release and by stimulating cAMP synthesis. The
      IC50 value of TE for ADP-induced platelet aggregation was 0.4 +/- 0.02 mg/ml,
      whereas the IC50 value for ACE enzyme inhibition was 1.40 +/- 0.04 mg/ml. Both
      the TE and commercially available sugar-free TE, Fruitflow((r))-2 had similar
      amount of catechin, and also had equal inhibitory potencies against platelet
      aggregation and plasma ACE activity. CONCLUSION: Together these data indicate
      that aqueous extract of tomatoes contain anti-ACE factors in addition to
      previously described anti-platelet factors.

PMID- 24573419
TI  - Identification, expression and function of apolipoprotein E in annual fish
      Nothobranchius guentheri: implication for an aging marker.
AB  - Apolipoprotein E (apoE) is a lipid-associated protein present in both plasma and
      in central nervous system. Variation in apoE gene has been reported to be
      associated with longevity in humans as well as with aged diseases such as
      atherosclerosis, Alzheimer's disease, and Parkinson's disease. However,
      information regarding the function and structure-activity relationship of apoE in
      lower vertebrates is rather limited. In this study we show that the apoE gene
      from the annual fish Nothobranchius guentheri, NapoE, encodes a protein of 262
      amino acids, which shares common structural features characteristic of mammalian
      apoE. We also show that like human apoE, recombinant NapoE is able to inhibit LDL
      oxidation, and it is the N-terminal domain of NapoE with lysine or arginine
      residues that plays a key role in inhibition of LDL oxidation. NapoE is
      predominantly expressed in the liver of N. guentheri, consistent with that in
      mammalian species. More importantly, we demonstrate an age-dependent down
      regulation of NapoE gene, rendering it a suitable biomarker of aging. This lays a
      foundation for further study of the role of apoE in the aging process of fish. 

PMID- 24573420
TI  - Factors affecting the intention and decision to be treated for obstructive sleep
      apnea disorder.
AB  - BACKGROUND AND PURPOSE: Obstructive sleep apnea (OSA) disorder has a deleterious
      impact on health. Using the continuous positive airway pressure (CPAP) device
      effectively lessens OSA. The purpose of this study was to examine the factors
      affecting patients' intention and actual decision to get treatment. METHODS:
      Questionnaires were distributed at three sleep laboratories in Israel among 633
      participants suspected of having OSA. Six months later, 194 OSA patients were
      contacted to verify whether they had purchased a CPAP device. RESULTS: Factors
      affecting intention to use the device included Health Belief Model variables,
      income level, and sleep laboratory location. The decision to get treatment was
      positively affected by the intention to use CPAP, the number of CPAP trial days,
      age, and number of years in the country. CONCLUSIONS: Patients' attitudes and
      health beliefs prior to diagnosis may predict their intention to be treated for
      OSA, and in turn, affect their actual decision to get treatment. Awareness of
      behavioral intention can enable decision makers developing targeted interventions
      to promote treatment.

PMID- 24573421
TI  - Parthenolide exerts inhibitory effects on angiogenesis through the downregulation
      of VEGF/VEGFRs in colorectal cancer.
AB  - Parthenolide (PT) is responsible for the bioactivities of feverfew (Tanacetum
      parthenium). Apart from its potent anti-inflammatory effects, this compound has
      been reported to induce apoptosis in various cancer cells. However, little is
      known about its role in the process of tumor angiogenesis. In the present study,
      we investigated the effects and potential mechanisms of action of PT on
      angiogenesis in human colorectal cancer (CRC). The anti-angiogenic effects of PT
      were evaluated in cultured human umbilical vein endothelial cells (HUVECs) and in
      the human CRC cell lines, HT-29, SW620 and HCT116. PT markedly inhibited vascular
      cell migration and capillary-like structure formation even at a dose which had
      not effects on cell viability. PT also suppressed the expression of angiogenic
      biomarker proteins [vascular endothelial growth factor (VEGF), VEGF receptor
      (VEGFR)1 and VEGFR2] in both the HUVECs and CRC cells. Additionally, PT
      effectively inhibited tumor neovascularization in a HT-29 xenograft model. These
      results indicate that PT suppresses angiogenesis by reducing the expression of
      VEGF and its receptors and may be a viable drug candidate in anti-angiogenesis
      therapies for human CRC. 

PMID- 24573423
TI  - Online First publication.

PMID- 24573422
TI  - Risk evaluation and mitigation strategy programs in solid organ transplantation:
      the promises of information technology.
AB  - Risk evaluation and mitigation strategies (REMS) required by the Food and Drug
      Administration are implemented to manage known or potential risks associated with
      medications and to ensure ongoing safe use throughout the life of a
      pharmaceutical agent. Healthcare organizations have begun to adopt information
      technologies with clinical decision support (CDS) to ensure safe use of
      medications. Systems have been expanded and customized to also ensure compliance
      with regulatory standards. End users who are unfamiliar with particular
      medication use provisions are at risk of unknowingly inappropriately fulfilling
      specific components. Institution-specific customization of vendor-provided CDS is
      useful to enhance provider awareness and ensure compliance with standards.
      Integration of health information technology systems to fulfill REMS requirements
      is novel and important to ensure consistency as healthcare standards evolve. 

PMID- 24573424
TI  - Apomixis in agriculture: the quest for clonal seeds.
AB  - Apomixis, or asexual reproduction through seeds, is a natural trait that could
      have an immense positive impact on crop production. Apomictic breeding strategies
      could allow the fixation and indefinite propagation of any desired genotype,
      however complex. Apomicts display a wide variety of developmental mechanisms,
      which can be viewed as a short-circuiting of sexual development. Gametophytic and
      sporophytic apomixis are distinguished by the developmental origin of
      apomictically derived embryos. Genetic studies suggest that individual elements
      of gametophytic apomixis, such as apomeiosis and parthenogenesis, are either
      controlled by one or two dominant Mendelian factors. As recombination around
      apomeiosis loci is suppressed, it is currently not known how complex these loci
      are. Much less is known regarding the genetic control of sporophytic apomixis but
      initial studies suggest a complex genetic control. Genetic analyses of sexual
      reproduction in plant model systems have identified genes that, when mutated,
      display elements of apomixis. Such studies help in the identification of
      candidate genes and promoters that can be used for the de novo engineering of
      apomixis through biotechnology. Molecular genetic studies in apomictic and sexual
      systems will generate the knowledge necessary for the engineering of conditional
      apomixis technology. Approaches encouraging collaboration and widespread
      dissemination of the acquired knowledge will constitute the most innovative route
      to the development, deployment and acceptance of apomixis technology in
      agriculture. 

PMID- 24573425
TI  - Autonomous endosperm development in flowering plants: how to overcome the
      imprinting problem?
AB  - In the vast majority of sexually reproducing flowering plants, a ratio of 2
      maternally derived genomes to 1 paternally derived genome (2m:1p) is essential
      for normal endosperm development, and therefore ultimately for seed development.
      Even in many pseudogamous apomicts, where the embryo develops without a paternal
      contribution, fertilisation of the endosperm to obtain the correct 2m:1p parental
      ratio is still necessary. How do autonomous apomicts, where both embryo and
      endosperm develop autonomously, circumvent this requirement? The background for
      the 2m:1p requirement is that the parental genomes are epigenetically different;
      in either genome, a set of genes is silenced in a sex-specific way by genomic
      imprinting. Removal of the imprints from the maternally derived endosperm genome
      leads to expression of normally maternally silenced genes, and effectively
      supplies the missing paternal genome. In Arabidopsis, we propose that a
      combination of the fie mutation and hypomethylation of the genome creates such a
      situation in the endosperm genome. As a result, in a fie mutant, hypomethylated
      ovule complete autonomous endosperm development takes place in the absence of
      fertilisation. 

PMID- 24573426
TI  - Reproductive development in apomictic populations of Arabis holboellii
      (Brassicaceae).
AB  - Megasporogenesis, megagametogenesis and seed formation were analyzed
      cytologically in populations of Arabis holboellii originating from North America
      (Colorado) and Greenland. The Colorado population contained only triploid plants,
      while the Greenland population consisted of diploid and triploid plants. The
      penetrance of the apomictic trait was assessed at the level of embryo sac
      development. All populations showed facultative apomeiotic embryo sac
      development; however the penetrance of this trait differed between the
      populations. Apomeiotic and meiotic embryo sac development were characterized by
      diplosporous dyad formation (Taraxacum-type) and meiotic tetrad formation
      (Polygonum-type), respectively. Flow cytometric analyses of single mature seeds
      from all three populations suggest that only unreduced gametes participate in
      viable seed development. Pseudogamy was the predominant mode of endosperm
      formation; however, autonomous endosperm development was also observed. The
      fertilization of unreduced egg cells with unreduced pollen was observed at a low
      frequency in the Greenland populations. The mechanisms of apomictic reproduction
      in A. holboellii are discussed. 

PMID- 24573427
TI  - Apomixis and sexuality in Paspalum simplex: characterization of the mode of
      reproduction in segregating progenies by different methods.
AB  - Segregating progenies of crosses between sexual and apomictic genotypes of
      Paspalum simplex were analysed for the formation of meiotic versus aposporous
      embryo sacs, zygotic versus parthenogenetic embryos, and autonomous versus
      pseudogamous endosperms by using cytoembryological and flow cytometric analyses.
      Reduced and unreduced 8-nucleated embryo sacs were the final product of female
      gametophyte development in sexual and aposporous genotypes, respectively. An
      incomplete penetrance of parthenogenesis was detected in aposporous genotypes.
      The relative DNA content of endosperm nuclei revealed the normal 2:1 maternal to
      paternal ratio in sexuals and a 4:1 ratio in apomicts, indicating insensitivity
      of the apomictic genotypes to endosperm imprinting. Apospory, parthenogenesis and
      pseudogamy are located on a relatively large linkage group and are inherited
      together with previously developed molecular markers as a single genetic unit in
      segregating progenies. 

PMID- 24573428
TI  - Direct evidence of pseudogamy in apomictic Brachiaria brizantha (Poaceae).
AB  - Brachiaria brizantha is a forage grass that has several apomictic accessions. B.
      brizantha cv. Marandu is a natural tetraploid aposporous apomict widely
      cultivated in Brazil. Pseudogamy was detected in this species by observation that
      seed set is suppressed in plants that have had the stigmas excised from the
      flowers. The egg cell develops parthenogenetically in the apomictic plants,
      meaning that fertilisation is necessary for the formation of the endosperm. A
      thorough knowledge of all the events of seed formation in natural apomictic
      plants is essential for a complete understanding of this mode of reproduction. In
      this paper, we show direct evidence of pseudogamy in B. brizantha through the
      cytological analysis of polar nucleus fertilisation and the determination of
      triploid level of the endosperm tissue. The development of the male gametophyte
      gives rise to a reduced tri-celled pollen, the viability of which varies
      throughout the year, reaching 88% in the peak of the flowering period. Discharge
      of the male gamete takes place around 10 h after pollination and monospermy is
      the predominant system observed. Precocious embryony was also observed in these
      plants; embryos arise from egg cells. Endosperm development followed the free
      nucleus model and was associated with the presence of an embryo. Cellularisation
      and reserve uptake occurred 2 days after pollination (DAP) and mature endosperm
      was observed 8 DAP. The triploid level of the endosperm in the apomictic
      accession confirmed the 2:1 maternal:paternal ratio of genome contribution in the
      tissue. 

PMID- 24573429
TI  - Apospory and parthenogenesis may be uncoupled in Poa pratensis: a cytological
      investigation.
AB  - Despite the potential that apomixis has for agriculture, there is little
      information regarding the genetic control of its functional components. We
      carried out a cytohistological investigation on an F1 segregating population of
      Poa pratensis obtained from a cross between a sexual and an apomictic parent.
      About half of the F1 progeny plants were parthenogenic, as adjudicated by an
      auxin test. The degree of parthenogenesis ranged from 1.44% to 92.9%. Apospory
      was detected in parthenogenetic plants as well as in two non-parthenogenetic
      individuals. These results indicate that two distinct genetic factors control
      apospory and parthenogenesis in P. pratensis and that apospory and
      parthenogenesis may be developmentally uncoupled. 

PMID- 24573430
TI  - Tripsacum dactyloides (Poaceae): a natural model system to study parthenogenesis.
AB  - Diplosporous apomeiosis, formation of unreduced embryo sacs primarily of the
      Antennaria type, followed by parthenogenetic embryo development and pseudogamy
      (fertilization of the central cell) describe gametophytic apomixis within the
      Tripsacum agamic complex. Tripsacum dactyloides (Eastern gamagrass) is a close
      relative of domesticated maize and was chosen as a natural model system to
      investigate gene expression patterns associated with parthenogenesis. The genome
      size of diploid sexual and polyploid apomictic T. dactyloides was estimated by
      flow cytometry to be 7.37 pg (2C), 14.74 pg (4C) and 22.39 pg (6C), respectively.
      The diploid genome size is thus approximately 1.35* larger than that of maize.
      The apomeiotic-pseudogamous pathway of seed formation was demonstrated at a rate
      of 92% by the flow cytometric seed screen (FCSS) with single mature seeds in
      tetraploid accessions. This number includes twin embryos which were detected in
      13% of the seeds analyzed. Fertilization of unreduced egg cells (BIII hybrids)
      was measured in 10% of apomictic seeds. Autonomous (fertilization-independent)
      embryo development and fertilization-dependent endosperm formation were confirmed
      by pollination of tetraploid T. dactyloides with a diploid transgenic maize line
      carrying an actin:: beta -glucuronidase (GUS) reporter construct. GUS expression
      was detected after pollination in the developing endosperm, but not in the
      embryo. In similar intraspecific crossing experiments with maize, GUS expression
      was detected in both the embryo and endosperm. A protocol was established for
      microdissection of embryo sacs and early parthenogenetic embryos of T.
      dactyloides. Together, these techniques provide new tools for future studies
      aimed at comparing gene expression patterns between sexual maize and sexual or
      apomictic T. dactyloides. 

PMID- 24573431
TI  - Strategies for isolating mutants in Hieracium with dysfunctional apomixis.
AB  - Species in the genus Hieracium subgenus Pilosella form asexual seed by the
      mechanism of apospory. We have reported previously that the capacity to be
      apomictic is inherited in these plants as a dominant trait at a single locus. The
      level of expression, however, is under the influence of a number of unlinked
      modifier loci. Several strategies are now being employed to identify and test
      sequences from these plants that may be involved in the control of this trait. An
      enhancer trap element, based on the Activator/Dissociator (Ac/Ds) transposons of
      maize and the beta glucuronidase reporter sequence, has been introduced into
      Hieracium. Introduced copies have been demonstrated to transpose in response to
      the co-introduction of a stabilized copy of Ac-transposase. Mutants are also
      being isolated following gamma irradiation of seed, and non-targeted T-DNA
      mediated mutagenesis. A total of 69 stable mutants were isolated following the
      gamma irradiation of asexual seed. These are currently undergoing histological
      analysis. A further two mutants, isolated from amongst the products of
      Agrobacterium-mediated transformation experiments, have lost apomixis yet retain
      sexuality. In one mutant, the loss of apomixis appears to be associated with a
      failure to form aposporous initials. Although asexual seed formation has been
      lost in this plant, no compensatory increase in sexuality was seen. Conversely,
      in the second mutant, aposporous initials were seen to begin differentiation but
      not to divide. Unlike the first mutant, the meiotic apparatus in this plant
      continued to develop normally and compensating sexuality was observed. 

PMID- 24573432
TI  - Analysis of gene expression during flowering in apomeiotic mutants of Medicago
      spp.: cloning of ESTs and candidate genes for 2n eggs.
AB  - Mutants showing features of apomixis have been documented in alfalfa (Medicago
      sativa L.), a natural outcrossing sexual species. A differential display of mRNAs
      that combines cDNA-AFLP markers and bulked segregant analysis was carried out
      with the aim of selecting expressed sequence tags (ESTs) and cloning candidate
      genes for apomeiosis in mutants of alfalfa characterized by 2n egg formation at
      high frequencies. The approach enabled us to select either mutant- or wild type
      specific transcript derived-fragments and to detect transcriptional changes
      potentially related to 2n eggs. Sequence alignments of a subset of 40 polymorphic
      clones showed significant homologies to genes of known function. An EST with
      identity to a beta-tubulin gene, highly expressed in the wild type and poorly
      expressed in the apomeiotic mutants, and an EST with identity to a Mob1-like
      gene, qualitatively polymorphic between pre- and post-meiotic stages, were
      selected as candidate genes for apomeiosis because of their putative roles in the
      cell cycle. A number of clone-specific primers were designed for performing both
      5' and 3' rapid amplification of cDNA ends to obtain the full-length clones.
      Southern blot hybridization revealed that both clones belong to a multi-gene
      family with a minimum of three genomic DNA members each. Northern blot
      hybridization of total RNA samples and in situ hybridization of whole buds
      enabled the definition of their temporal and spatial expression patterns in
      reproductive organs. Experimental achievements towards the elucidation of
      apomeiotic megasporogenesis in alfalfa are presented and discussed. 

PMID- 24573433
TI  - Parthenogenetic egg cells of wheat: cellular and molecular studies.
AB  - The 'Salmon' system of wheat comprises three isogenic alloplasmic lines with
      either zygotic (aS) or autonomous, fertilisation-independent (cS kS) embryo
      development. While the initiation of embryogenesis from the isolated sexual egg
      cell depends on in vitro fertilisation, the corresponding parthenogenetic egg
      cell develops into an early embryo without fertilisation. This demonstrates that
      parthenogenesis is an inherent feature of the isolated egg cell. Based on this
      observation, we have constructed egg-cell-specific cDNA libraries and report
      first results of a sequencing project aimed at the isolation of putative egg-cell
      specific and parthenogenesis-related genes. 

PMID- 24573434
TI  - 2nd International Apomixis Conference (AP02001) at Como, Italy, 24-28 April 2001.

PMID- 24573438
TI  - From promiscuity to the lipid divide: on the evolution of distinct membranes in
      Archaea and Bacteria.
AB  - The structural and biosynthetic features of archaeal phospholipids provide clues
      to the membrane lipid composition in the last universal common ancestor (LUCA)
      membranes. The evident similarity of the phospholipid biosynthetic pathways in
      Archaea and Bacteria suggests that one set of these biosynthetic enzymes would
      have worked on a wide range of lipids composed of enantiomeric glycerophosphate
      backbones linked with a variety of hydrocarbon chains. This notion was supported
      by the discovery of a wide range reactivity of enzymes belonging to the CDP
      alcohol phosphatidyltransferase family. It is hypothesized that lipid promiscuity
      is generated from the prebiotic surface metabolism on pyrite proposed by
      Wachtershauser. The significance of the phosphate groups on the intermediates of
      phospholipid biosynthesis and the extra anionic groups of a polar head group
      suggested the likely involvement of surface metabolism. Anionic groups are
      essential for surface metabolism. Since the early chemical evolution reactions
      are presumed to be non-specific, every combination of the available lipid
      component parts would be expected to be formed. The mixed lipid membranes present
      in LUCA were segregated and this led to the differentiation of Archaea and
      Bacteria, as described previously. The proper arrangement of membrane lipids was
      generated by the physicochemical drive arising from the promiscuity of the
      primordial membrane lipids. 

PMID- 24573439
TI  - Protective effects of the SEPS1 gene on lipopolysaccharide-induced sepsis.
AB  - Septic shock and sequential multiple organ failure are the main cause of
      mortality in patients with sepsis. The induction of inflammation during sepsis is
      a complex biological cascade, which requires successful therapeutic intervention.
      Selenoprotein S (SEPS1) is a novel endoplasmic reticulum-resident protein and is
      important in the production of inflammatory cytokines. The present study
      attempted to assess the effect of SEPS1 suppression by small interfering RNA
      (siRNA) on mice with lipopolysaccharide (LPS)-induced sepsis. In total, 30 mice
      were randomly assigned to three groups: i) H group (LPS-induced sepsis group;
      n=10): Mice with intraperitoneal injection of LPS (10 mg/kg); ii) K group
      (scrambled siRNA group; n=10): Mice transfected with scrambled control siRNA 12 h
      prior to injection with LPS and iii) L group (SEPS1 siRNA group; n=10): Mice
      transfected with SEPS1 siRNA 12 h prior to injection with LPS. The effects of
      siRNA were evaluated by SEPS1 gene and protein expression, biochemical parameters
      including serum alanine transaminase (ALT), aspartate aminotransferase (AST),
      blood urea nitrogen (BUN), lactic dehydrogenase (LDH), creatine kinase (CK) and
      myocardial kinase (CK-MB), as well as the cytokines interleukin-6 (IL-6) and
      tumor necrosis factor-alpha (TNF-alpha). The phosphorylation of p38 mitogen
      activated protein kinases (p38 MAPK) was also detected by western blot analysis.
      In the SEPS1 siRNA group, SEPS1 gene and protein expression decreased
      significantly, while the levels of TNF-alpha and IL-6 increased compared with the
      control group. The biochemical parameters of ALT, AST, BUN, LDH, CK and CK-MB
      were markedly increased in the SEPS1 siRNA group. The phosphorylation of p38 MAPK
      was also significantly activated. The decrease in SEPS1 gene and protein
      expression and the production of TNF-alpha and IL-6 may correlate with the
      activation of the p38 MAPK pathway. Biochemical factors and pathological results
      demonstrated that the damage to vital organs was aggravated. In conclusion, these
      findings suggested that SEPS1 may protect mice against LPS-induced sepsis and
      organ damage. Therefore, SEPS1 may be a new target to resolve LPS-induced sepsis.

PMID- 24573441
TI  - Monitoring the shape evolution of Pd nanocubes to octahedra by PdS frame markers.
AB  - We report the use of compounds formed on the surface of nanocrystals as markers
      to effectively monitor the shape evolution during nanocrystal growth. By
      labelling the corners and edges of cubic Pd seeds with PdS through sulfuration,
      we obtain clear insight into their shape transition to octahedra. This work
      significantly expands the scope of the marker technique for studying nanoparticle
      shape evolution. 

PMID- 24573440
TI  - Livistona chinensis seeds inhibit hepatocellular carcinoma angiogenesis in vivo
      via suppression of the Notch pathway.
AB  - Livistona chinensis seeds have been used for centuries to clinically treat
      various types of cancer. Our published data suggest that Livistona chinensis
      seeds are able to inhibit hepatocellular carcinoma (HCC) growth in vitro and in
      vivo via promotion of mitochondrial-dependent apoptosis. To further elucidate the
      molecular mechanisms of its antitumor activity, in the present study, we used an
      HCC xenograft mouse model to evaluate the effect of an ethanol extract of
      Livistona chinensis seeds (EELC) on tumor angiogenesis and on the activation of
      the Notch pathway. Intratumoral microvessel density (MVD) in HCC xenograft mouse
      tumors was evaluated via immunohistochemical (IHC) staining for CD31. The mRNA
      and protein expression of vascular endothelial growth factor A (VEGF-A), VEGFR-2,
      Notch, Dll4 and Jagged1 was evaluated using RT-PCR and IHC, respectively. We
      found that EELC profoundly reduced MVD in the HCC mouse tumors, demonstrating the
      in vivo inhibitory effect of EELC on tumor angiogenesis. In addition, EELC
      treatment reduced the expression of VEGF-A and VEGFR-2 in tumor tissues.
      Furthermore, EELC treatment inhibited the expression of Notch, Dll4 and Jagged1.
      Our findings suggest that Livistona chinensis seeds inhibit tumor angiogenesis
      through suppression of the Notch pathway.

PMID- 24573442
TI  - Efficient in vivo gene delivery using modified Tat peptide with cationic lipids.
AB  - A combination of modified HIV-1 Tat (mTat) peptide and cationic lipids, FuGENE HD
      (FH), dramatically enhanced transfection efficiency across a range of cell lines
      when compared to mTat or FH alone (Biomaterials 35:1705-1715 2014). The
      efficiency of this Tat peptide combination was significantly higher than many
      commercial non-viral vectors. In this present study, we tested the feasibility of
      this non-viral vector, mTat/FH, in vivo using plasmid DNA encoding a luciferase
      gene. The results of the in vivo studies showed that animals administered
      mTat/FH/DNA intramuscularly had significantly higher and longer luciferase
      expression (~7 months) than those with mTat/DNA, FH/DNA, or DNA alone.
      Histological evaluation showed little immune response in the muscles, livers, and
      kidneys of mice administered with the mTat/FH. The combination of mTat with FH
      could significantly improve transfection efficiency, expanding the potential use
      of non-viral gene vectors in vivo. 

PMID- 24573443
TI  - Bioreactors for plant cells: hardware configuration and internal environment
      optimization as tools for wider commercialization.
AB  - Mass production of value-added molecules (including native and heterologous
      therapeutic proteins and enzymes) by plant cell culture has been demonstrated as
      an efficient alternative to classical technologies [i.e. natural harvest and
      chemical (semi)synthesis]. Numerous proof-of-concept studies have demonstrated
      the feasibility of scaling up plant cell culture-based processes (most notably to
      produce paclitaxel) and several commercial processes have been established so
      far. The choice of a suitable bioreactor design (or modification of an existing
      commercially available reactor) and the optimization of its internal environment
      have been proven as powerful tools toward successful mass production of desired
      molecules. This review highlights recent progress (mostly in the last 5 years) in
      hardware configuration and optimization of bioreactor culture conditions for
      suspended plant cells. 

PMID- 24573444
TI  - The theoretical root of Karl Jaspers' General Psychopathology. Part 2: The
      influence of Max Weber.
AB  - The present study explores and compares Jaspers' methodology of psychopathology
      with Weber's methodology of sociology. In his works, Weber incorporated the
      arguments of many other researchers into his own methodology. Jaspers respected
      Weber as a mentor and presented arguments that were very similar to Weber's. Both
      Weber and Jaspers began from empathic understanding, but at the same time aimed
      for a rational and ideal-typical conceptualization. In addition, their
      methodologies were similar with respect to their detailed terminology. Such
      similarities cannot be seen with any other scholars. This suggests that Weber may
      have played an integral role as a mediator between his contemporary scholars and
      Jaspers. Thus, Weber may have had the most significant influence on Jaspers. 

PMID- 24573445
TI  - The Bavarian royal drama of 1886 and the misuse of psychiatry: new results.
AB  - The deaths of King Ludwig II of Bavaria and Bernhard von Gudden, Professor of
      Psychiatry in Munich, in Lake Starnberg near Munich on 13 June 1886 have often
      been mentioned in the psychiatric-historical literature and in fiction. Von
      Gudden had written a psychiatric assessment of the King, rating him permanently
      mentally ill and incapable of reigning. Ludwig II was declared legally
      incapacitated, dethroned and psychiatrically interned. We will report on an
      interdisciplinary research project conducted at the Heidelberg Academy of
      Sciences and Humanities. Information was collected from state, local and private
      archives in Germany and abroad on: (1) the correctness of the psychiatric
      assessment in form and content; (2) the constitutional basis of the deposition;
      and (3) its background, motives and execution. The results show that the
      psychiatric assessment was incorrect in substance and form. They highlight how
      those in power used psychiatry for their own purposes. 

PMID- 24573446
TI  - Mental health issues of Maria I of Portugal and her sisters: the contributions of
      the Willis family to the development of psychiatry.
AB  - Contemporary accounts credit Dr Francis Willis (1718-1807) with facilitating the
      recovery of King George III from his major episode of acute mania in 1788-9.
      Subsequently Willis was summoned to Lisbon to advise on the mental health
      problems of Queen Maria I. This article reports the nature of the illnesses of
      Maria and her two similarly affected sisters, and uses the program OPCRIT to
      propose diagnoses of major depressive disorders. The high prevalence of
      consanguinity and insanity among the Portuguese monarchy and their antecedents
      probably contributed to their mental health problems. The successive
      contributions of the Willis family from Thomas Willis (1621-75) to his grand
      nephew, Francis Willis (1792-1859), are reviewed; the popular image is somewhat
      inaccurate and does not highlight their part in the development of psychiatry. 

PMID- 24573447
TI  - Psychodynamics in child psychiatry in Sweden, 1945-85: from political vision to
      treatment ideology.
AB  - In this article, changing treatment ideologies and policies in child psychiatric
      outpatient services in Sweden from 1945 to 1985 are examined. The aim is to
      discuss the role played by psychoanalytic and psychodynamic thinking in this
      process of change. When mental health services for children were introduced in
      the mid-1940s, psychoanalytic thinking was intertwined with the social democratic
      vision of the Swedish welfare state in which children symbolized the future. In
      practice, however, treatment ideology was initially less influenced by
      psychoanalytic thinking. From the early 1960s, child psychiatric services
      expanded and the number of units increased. By then, the political vision had
      disappeared, but a treatment ideology began to evolve based on psychodynamic
      theories, which became dominant in the 1970s. 

PMID- 24573448
TI  - The birth and death of Villa 21.
AB  - From 1962 to 1966 David Cooper ran an experimental hospital ward in Villa 21 of
      Shenley Hospital, Hertfordshire, England. In the histories of mid-twentieth
      century psychiatry and anti-psychiatry, this ward has been almost entirely
      forgotten, overshadowed by the figure of R.D. Laing and his Kingsley Hall
      experiment. This study attempts to construct a history of Villa 21 and to
      reassert its historical importance as a manifestation of British anti-psychiatry
      and the radically anti-institutional politics of its time. Beginning before the
      opening of the ward, this article follows the story of Villa 21 on theoretical,
      practical and personal levels through its experimental journey and into its
      dramatic aftermath when Cooper's experiment was ideologically obliterated by his
      successor Michael Conran and physically obliterated by the Hospital
      administration. It contends that Villa 21 is an example of anti-psychiatry's
      attempt to engage with the very structure of society at a profound level. 

PMID- 24573449
TI  - Battling demons with medical authority: werewolves, physicians and
      rationalization.
AB  - Werewolves and physicians experienced their closest contact in the context of
      early modern witch and werewolf trials. For medical critics of the trials,
      melancholic diseases served as reference points for medical explanations of both
      individual cases and werewolf beliefs in general. This paper attempts to
      construct a conceptual history of werewolf beliefs and their respective medical
      responses. After differentiating the relevant terms, pre-modern werewolf concepts
      and medical lycanthropy are introduced. The early modern controversy between
      medical and demonological explanations forms the main part of this study. The
      history of werewolves and their medical explanations is then traced through to
      present times. An important point of discussion is to what extent the physicians'
      engagements with werewolves can be characterized as rationalization. 

PMID- 24573450
TI  - 'Pauper Lunatics and their Treatment', by Joshua Harrison Stallard (1870).
AB  - Little is known of Joshua Harrison Stallard other than that he was a provincial
      medical practitioner who moved to London and campaigned for improvement in
      metropolitan workhouses. In the pamphlet reproduced here, Stallard draws
      attention to the build-up of lunatics in workhouses due to lack of asylum beds.
      He also argues for the increased use of home care for lunatics instead of
      continually expanding asylum provision, and points to the need for training of
      asylum doctors. 

PMID- 24573453
TI  - Research on the history of psychiatry: Dissertation Abstracts, 2010-11 (Part 2).

PMID- 24573454
TI  - Otto m. Marx, 1929-2012.

PMID- 24573455
TI  - An adsorbent monolith device to augment the removal of uraemic toxins during
      haemodialysis.
AB  - Adsorbents designed with porosity which allows the removal of protein bound and
      high molecular weight uraemic toxins may improve the effectiveness of
      haemodialysis treatment of chronic kidney disease (CKD). A nanoporous activated
      carbon monolith prototype designed for direct blood contact was first assessed
      for its capacity to remove albumin bound marker toxins indoxyl sulphate (IS), p
      cresyl sulphate (p-CS) and high molecular weight cytokine interleukin-6 in spiked
      healthy donor studies. Haemodialysis patient blood samples were then used to
      measure the presence of these markers in pre- and post-dialysis blood and their
      removal by adsorbent recirculation of post-dialysis blood samples. Nanopores (20
      100 nm) were necessary for marker uraemic toxin removal during in vitro studies.
      Limited removal of IS and p-CS occurred during haemodialysis, whereas almost
      complete removal occurred following perfusion through the carbon monoliths
      suggesting a key role for such adsorbent therapies in CKD patient care.

PMID- 24573456
TI  - Multifunctional substrates of thin porous alumina for cell biosensors.
AB  - We have fabricated anodic porous alumina from thin films (100/500 nm) of
      aluminium deposited on technological substrates of silicon/glass, and
      investigated the feasibility of this material as a surface for the development of
      analytical biosensors aiming to assess the status of living cells. To this goal,
      porous alumina surfaces with fixed pitch and variable pore size were analyzed for
      various functionalities. Gold coated (about 25 nm) alumina revealed surface
      enhanced Raman scattering increasing with the decrease in wall thickness, with
      factor up to values of approximately 10(4) with respect to the flat gold surface.
      Bare porous alumina was employed for micro-patterning and observation via
      fluorescence images of dye molecules, which demonstrated the surface capability
      for a drug-loading device. NIH-3T3 fibroblast cells were cultured in vitro and
      examined after 2 days since seeding, and no significant (P > 0.05) differences in
      their proliferation were observed on porous and non-porous materials. The effect
      on cell cultures of pore size in the range of 50-130 nm--with pore pitch of about
      250 nm--showed no significant differences in cell viability and similar levels in
      all cases as on a control substrate. Future work will address combination of all
      above capabilities into a single device.

PMID- 24573457
TI  - An in vivo murine model for screening cranial bone regenerative materials:
      testing of a novel synthetic collagen gel.
AB  - Rapid and efficient animal models are needed for evaluating the effectiveness of
      many new candidate bone regenerative materials. We developed an in vivo model
      screening for calvarial bone regeneration in lipopolysaccharide (LPS)-treated
      mice, in which materials were overlaid on the periosteum of the calvaria in a 20
      min surgery and results were detectable in 1 week. Intraperitoneal LPS injection
      reduced spontaneous bone formation, and local application of basic fibroblast
      growth factor (bFGF) increased the bone-forming activities of osteoblasts. A
      novel synthetic collagen gel, alkali-treated collagen (AlCol) cross-linked with
      trisuccinimidyl citrate (TSC), acted as a reservoir for basic substances such as
      bFGF. The AlCol-TSC gel in conjunction with bFGF activated osteoblast activity
      without the delay in osteoid maturation caused by bFGF administration alone. The
      AlCol-TSC gel may slow the release of bFGF to improve the imbalance between
      osteoid formation and bone mineralization. These findings suggest that our model
      is suitable for screening bone regenerative materials and that the AlCOl-TSC gel
      functions as a candidate reservoir for the slow release of bFGF.

PMID- 24573458
TI  - Study on the efficiency of nanosized magnetite and mixed ferrites in magnetic
      hyperthermia.
AB  - Magnetic materials, which have the potential for application in heating therapy
      by hyperthermia, were prepared. This alternative treatment is used to eliminate
      cancer cells. Magnetite, magnesium-calcium ferrites and manganese-calcium
      ferrites were synthesized by sol-gel method followed by heat treatment at
      different temperatures for 30 min in air. Materials with superparamagnetic
      behavior and nanometric sizes were obtained in all the cases. Thus, these
      nanopowders may be suitable for their use in human tissue. The average sizes were
      14 nm for magnetite, 10 nm for both Mg(0.4)Ca(0.6)Fe(2)O(4) and
      Mg(0.6)Ca(0.4)Fe(2)O(4) and 11 nm for Mn(0.2)Ca(0.8)Fe(2)O(4). Taking into
      account that the Mg(0.4)Ca(0.6)Fe(2)O(4) and Mg(0.6)Ca(0.4)Fe(2)O(4) treated at
      350  degrees C showed the lower coercivity values, these nanoparticles were
      selected for heating tests and cell viability. Heating curves of
      Mg(0.4)Ca(0.6)Fe(2)O(4) subjected to a magnetic field of 195 kHz and 10 kA/m
      exhibited a temperature increase up to 45  degrees C in 15 min. A high human
      osteosarcoma cell viability of 90-99.5% was displayed. The human osteosarcoma
      cell with magnesium-calcium ferrites exposed to a magnetic field revealed a death
      cell higher than 80% in all the cases.

PMID- 24573459
TI  - Aqueous date fruit extract protects against lipid peroxidation and improves
      antioxidant status in the liver of rats subchronically exposed to trichloroacetic
      acid.
AB  - Trichloroacetic acid (TCA) is a prominent by-product of the chlorination of
      drinking water. It induces cell damage by producing free radicals and reactive
      oxygen species. The present study was carried out to evaluate the potential
      hepatoprotective role of the aqueous date extract (ADE) against TCA-induced liver
      injury. Forty-eight male Wistar rats were randomly divided into six groups of
      eight: group I served as the control; group II was given ADE by gavage; groups
      III and IV received TCA as drinking water at 0.5 and 2 g/L, respectively; and
      groups V and VI were treated with ADE by gavage and then received TCA at 0.5 and
      2 g/L, respectively, as drinking water. The experiment was performed for 2
      months. The hepatotoxicity of TCA administration was revealed by an increase in
      the levels of hepatic marker enzymes (transaminases, gamma-glutamyl transferase,
      and lactate dehydrogenase) and conjugated bilirubin and a decrease in albumin
      level. The TCA administration induced also significant elevation of the
      malondialdehyde (MDA) level and the antioxidant activity of superoxide dismutase
      (SOD) and glutathione peroxidase (GPx) paralleled with a significant decline in
      catalase (CAT) activity. These biochemical alterations were accompanied by
      histological changes marked by the appearance of vacuolization, necrosis,
      congestion, inflammation, and enlargement of sinusoids in the liver section.
      Treatment with date palm fruit extract restored the liver damage induced by TCA,
      as demonstrated by inhibition of hepatic lipid peroxidation; amelioration of SOD,
      GPx, and CAT activities; and improvement of histopathology changes. These results
      suggest that ADE has a protective effect over TCA-induced oxidative damage in rat
      liver. 

PMID- 24573460
TI  - Effects of di-n-butyl phthalate on the physiology and ultrastructure of cucumber
      seedling roots.
AB  - Agricultural pollution caused by the use of plastic sheetings has been documented
      to be a widespread problem in most of the major crop-planting regions of the
      world. In order to better understand the phytotoxic mechanisms induced by
      phthalic acid esters involved with this problem, Cucumber sativus L. cv Jinyan
      No. 4 were sown in pots to the three-leaf-stage in the presence of di-n-butyl
      phthalate (DBP; 0, 30, 50, 100, and 200 mg L(-1)) for 1, 3, 5, or 7 days.
      Physiology, biochemistry, and ultrastructure of seedling roots were examined. The
      results indicated that activities of three antioxidant enzymes (superoxide
      dismutase (SOD), catalase (CAT), and peroxidase (POD)) were stimulated at low-DBP
      treatments and decreased under higher levels (>100 mg L(-1)) compared to the
      controls. On the other hand, SOD and POD provided a better defense against DBP
      induced oxidative damage in the roots of cucumber seeding, compared to CAT. The
      productions of both malondialdehyde (MDA) and proline (Pro) were promoted under
      DBP stress. Visible impact on the cytoderm, mitochondrion, and vacuole was
      detected, possibly as a consequence of free radical generation. These results
      suggested that activation of the antioxidant system by DBP led to the formation
      of reactive oxygen species that resulted in cellular damage.

PMID- 24573461
TI  - Trace elements in sediments, blue spotted tilapia Oreochromis leucostictus
      (Trewavas, 1933) and its parasite Contracaecum multipapillatum from Lake
      Naivasha, Kenya, including a comprehensive health risk analysis.
AB  - This study presents the distribution of 15 major and trace elements in sediments
      and fish and their pericardial parasites from Lake Naivasha, Kenya. The lake is
      one of the few freshwater lakes in the Great Rift Valley and is under strong
      anthropogenic pressure mainly due to agricultural activities. Its fish provide a
      valuable protein source for approximately 100,000 people in the area. Fish and
      their parasites have been acknowledged as indicators of environmental quality due
      to their accumulation potential for both essential and nonessential trace
      elements. A total of 34 specimens of the blue spotted tilapia Oreochromis
      leucostictus and pooled samples of their pericardial parasite, the anisakid
      nematode Contracaecum multipapillatum (larvae 3), were examined. Element
      concentrations were determined by inductively coupled plasma-optical emission
      spectroscopy (ICP-OES) and graphite furnace atomic absorption spectrometry (GF
      AAS). The concentrations of elements in the sediments reflected the geology of
      the area and did not point to pollution: none of the investigated trace elements,
      including Pb, Cd, Cu, and Zn, showed elevated values. In contrast, concentrations
      in the fish muscle were elevated for Li, Sr, Cd, and Zn, with high target hazard
      quotients (THQ > 0.1) indicating a potential health risk to the consumers of this
      fish. Fish liver showed significantly higher concentrations of the trace elements
      Fe, Mn, Cd, and Cu compared to the muscle and C. multipapillatum. In the
      parasite, Zn had the highest concentration, but the worms only minimally
      accumulated trace elements in relation to their fish host. 

PMID- 24573462
TI  - Isovaleraldehyde elimination by UV/TiO2 photocatalysis: comparative study of the
      process at different reactors configurations and scales.
AB  - A proposal for scaling-up the photocatalytic reactors is described and applied to
      the coated catalytic walls with a thin layer of titanium dioxide under the near
      ultraviolet (UV) irradiation. In this context, the photocatalytic degradation of
      isovaleraldehyde in gas phase is studied. In fact, the removal capacity is
      compared at different continuous reactors: a photocatalytic cylindrical reactor,
      planar reactor, and pilot unit. Results show that laboratory results can be
      useful for reactor design and scale-up. The flowrate increases lead to the
      removal capacity increases also. For example, with pilot unit, when flowrate
      extends four times, the degradation rate varies from 0.14 to 0.38 g h(-1) mcat (
      2). The influence of UV intensity is also studied. When this parameter increases,
      both degradation rate and overall mineralization are enhanced. Moreover, the
      effects of inlet concentration, flowrate, geometries, and size of reactors on the
      removal capacity are also studied.

PMID- 24573463
TI  - Remediation of acid mine drainage (AMD)-contaminated soil by Phragmites australis
      and rhizosphere bacteria.
AB  - Experiments were conducted to assess the impact of citric acid (CA) and
      rhizosphere bacteria on metal uptake in Phragmites australis cultured in a spiked
      acid mine drainage (AMD) soil. Rhizosphere iron-oxidizing bacteria (Fe(II)OB)
      enhanced the formation of Fe plaque on roots, which decreased the uptake of Fe
      and Mn. CA inhibited the growth of Fe(II)OB, decreased the formation of metal
      plaque, raised the metal mobility in soil, and increased the accumulation of
      metals in all tissues of the reeds. The higher the CA dosage, the more metals
      accumulated into reeds. The total amount of metals in reeds increased from 7.8 +/
      0.5 * 10(-6) mol plant(-1) (Mn), 1.4 +/- 0.1 * 10(-3) mol plant(-1) (Fe), and
      1.0 +/- 0.1 * 10(-4) mol plant(-1) (Al) in spiked soil without CA to 22.2 +/- 0.5
      * 10(-6) mol plant(-1) (Mn), 3.5 +/- 0.06 * 10(-3) mol plant(-1) (Fe), and 5.0 +/
      0.2 * 10(-4) mol plant(-1) (Al) in soil added with 33.616 g C6H8O7.H2O for per
      kilogram soil. CA could be effective at enhancing the phytoremediation of metals
      from AMD-contaminated soil. 

PMID- 24573464
TI  - Fourteenth National Congress of the Environmental and Cultural Heritage Chemistry
      Division, "Chemistry in a Sustainable Society," held in Rimini (Italy) in June
      2013.
AB  - This report briefly presents the aims and the fields of interest of the
      Environmental and Cultural Heritage Division (Italian Chemical Society) and the
      issues addressed during its national congress, held in Rimini in June 2013. The
      broad range of topics raised by different speakers, the variety of affiliations
      and institutions participating at the conference, the scientific organisations
      and private companies co-sponsoring the different sessions give a clear picture
      of the interdisciplinarity which is a hallmark of this division. 

PMID- 24573465
TI  - Estimated crop yield losses due to surface ozone exposure and economic damage in
      India.
AB  - In this study, we estimate yield losses and economic damage of two major crops
      (winter wheat and rabi rice) due to surface ozone (O3) exposure using hourly O3
      concentrations for the period 2002-2007 in India. This study estimates crop yield
      losses according to two indices of O3 exposure: 7-h seasonal daytime (0900-1600
      hours) mean measured O3 concentration (M7) and AOT40 (accumulation exposure of O3
      concentration over a threshold of 40 parts per billion by volume during daylight
      hours (0700-1800 hours), established by field studies. Our results indicate that
      relative yield loss from 5 to 11% (6-30%) for winter wheat and 3-6% (9-16%) for
      rabi rice using M7 (AOT40) index of the mean total winter wheat 81 million metric
      tons (Mt) and rabi rice 12 Mt production per year for the period 2002-2007. The
      estimated mean crop production loss (CPL) for winter wheat are from 9 to 29 Mt,
      account for economic cost loss was from 1,222 to 4,091 million US$ annually.
      Similarly, the mean CPL for rabi rice are from 0.64 to 2.1 Mt, worth 86-276
      million US$. Our calculated winter wheat and rabi rice losses agree well with
      previous results, providing the further evidence that large crop yield losses
      occurring in India due to current O3 concentration and further elevated O3
      concentration in future may pose threat to food security.

PMID- 24573466
TI  - Concentration and characterization of airborne particles in Tehran's subway
      system.
AB  - Particulate matter is an important air pollutant, especially in closed
      environments like underground subway stations. In this study, a total of 13
      elements were determined from PM10 and PM2.5 samples collected at two subway
      stations (Imam Khomeini and Sadeghiye) in Tehran's subway system. Sampling was
      conducted in April to August 2011 to measure PM concentrations in platform and
      adjacent outdoor air of the stations. In the Imam Khomeini station, the average
      concentrations of PM10 and PM2.5 were 94.4 +/- 26.3 and 52.3 +/- 16.5 MUg m(-3)
      in the platform and 81.8 +/- 22.2 and 35 +/- 17.6 MUg m(-3) in the outdoor air,
      respectively. In the Sadeghiye station, mean concentrations of PM10 and PM2.5
      were 87.6 +/- 23 and 41.3 +/- 20.4 MUg m(-3) in the platform and 73.9 +/- 17.3
      and 30 +/- 15 MUg m(-3), in the outdoor air, respectively. The relative
      contribution of elemental components in each particle fraction were accounted for
      43% (PM10) and 47.7% (PM2.5) in platform of Imam Khomeini station and 15.9%
      (PM10) and 18.5% (PM2.5) in the outdoor air of this station. Also, at the
      Sadeghiye station, each fraction accounted for 31.6% (PM10) and 39.8% (PM2.5) in
      platform and was 11.7% (PM10) and 14.3% (PM2.5) in the outdoor. At the Imam
      Khomeini station, Fe was the predominant element to represent 32.4 and 36 % of
      the total mass of PM10 and PM2.5 in the platform and 11.5 and 13.3% in the
      outdoor, respectively. At the Sadeghiye station, this element represented 22.7
      and 29.8% of total mass of PM10 and PM2.5 in the platform and 8.7 and 10.5% in
      the outdoor air, respectively. Other major crustal elements were 5.8% (PM10) and
      5.3% (PM2.5) in the Imam Khomeini station platform and 2.3 and 2.4% in the
      outdoor air, respectively. The proportion of other minor elements was
      significantly lower, actually less than 7% in total samples, and V was the minor
      concentration in total mass of PM10 and PM2.5 in both platform stations.

PMID- 24573467
TI  - Exploring the role of a stigma-expressed plant U-box gene in the pollination
      responses of transgenic self-incompatible Arabidopsis thaliana.
AB  - Recognition of "self" pollen in the self-incompatibility (SI) response of the
      Brassicaceae is determined by allele-specific interaction between the S-locus
      receptor kinase (SRK), a transmembrane protein of the stigma epidermis, and its
      ligand, the pollen coat-localized S-locus cysteine-rich (SCR) protein. The
      current model for SRK-mediated signaling proposes a central role for the plant U
      box (PUB) Armadillo repeat-containing protein ARC1, an E3 ligase that interacts
      with, and is phosphorylated by, the kinase domain of SRK. According to the model,
      activated ARC1 causes the degradation of factors required for successful pollen
      tube growth. However, Arabidopsis thaliana plants transformed with functional SRK
      and SCR genes isolated from self-incompatible A. lyrata can express an intense SI
      response despite lacking a functional ARC1 gene. Here, we tested the possibility
      that a different member of the A. thaliana PUB protein family might have assumed
      the role of ARC1 in SI. Toward this end, we analyzed the AtPUB2 gene, which is
      annotated as being highly expressed in stigmas. Our functional analysis of a T
      DNA insertion pub2 allele, together with yeast two-hybrid interaction assays and
      reporter analysis of AtPUB2 promoter activity, demonstrates that AtPUB2 does not
      function in SI. The results leave open the question of whether the proposed model
      of ARC1-mediated signaling applies to transgenic SRK-SCR self-incompatible A.
      thaliana plants. 

PMID- 24573468
TI  - Smoking alters circulating plasma microvesicle pattern and microRNA signatures.
AB  - Circulating plasma microvesicles (PMVs) and their microRNA content are involved
      in the development of atherosclerosis and could serve as biomarkers for
      cardiovascular disease (CVD) progression. However, little is known on how smoking
      influences the levels of PMVs and microRNA signatures in vivo. Therefore, we
      aimed to investigate the effects of smoking on circulating PMV levels and CVD
      related PMV-derived microRNAs in young, healthy smokers. Twenty young (10 female,
      10 male; 25 +/- 4 years) healthy smokers (16 +/- 6 cigarettes per day for 8 +/- 4
      years) and age- and sex-matched controls were included in this study. While
      complete blood count revealed no differences between both groups, smoking
      significantly enhanced intracellular reactive oxygen species in platelets and
      leukocytes as well as platelet-leukocyte aggregate formation. Total circulating
      PMV counts were significantly reduced in smokers, which could be attributed to
      decreased platelet-derived PMVs. While the number of endothelial PMVs remained
      unaffected, smoking propagated circulating leukocyte-derived PMVs. Despite
      reduced total PMVs, PMV-derived microRNA-profiling of six smoker/control pairs
      revealed a decrease of only a single microRNA, the major platelet-derived
      microRNA miR-223. Conversely, miR-29b, a microRNA associated with aortic aneurysm
      and fibrosis, and RNU6-2, a commonly used reference-RNA, were significantly up
      regulated. Smoking leads to alterations in the circulating PMV profile and
      changes in the PMV-derived microRNA signature already in young, healthy adults.
      These changes may contribute to the development of smoking-related cardiovascular
      pathologies. Moreover, these smoking-related changes have to be considered when
      microRNA or PMV profiles are used as disease-specific biomarkers. 

PMID- 24573469
TI  - Epigenetic alterations in sporadic basal cell carcinomas.
AB  - Basal cell carcinoma (BCC) is the most common malignant human neoplasm
      characterized by slow growth and virtual absence of metastases. Recently, it has
      become evident that along with genetic mutations epigenetic alterations play a
      key role in the pathogenesis of human cancer. We searched for promoter
      methylation of hMLH1, RASSF1A, DAPK, APC, DCR1 and DCR2 genes and BRAF mutations
      in BCCs in association with the clinicopathological parameters and the
      histological subtypes of the tumours. Fifty-two BCCs, 17 FFPE along with 35 fresh
      tissue samples with matching normal tissues for 26 cases were analyzed by
      methylation-specific PCR to assess the methylation status of hMLH1, RASSF1A,
      DAPK, APC, DCR1 and DCR2 genes after sodium bisulfite treatment of the tumour and
      normal DNA. hMLH1 and DCR1 gene expression was investigated by
      immunohistochemistry. BRAF mutations were studied by high resolution melting
      analysis. Methylation was detected at a variable frequency of 44, 33, 32.5, 32
      and 14 % of DCR2, APC, DCR1, RASSF1 and DAPK promoters, respectively, whereas
      methylation of hMLH1 promoter was absent. No BRAF mutations were found. There was
      no correlation between the frequency of the promoter methylation of the above
      mentioned genes and the clinicopathological features or the histological subtypes
      of the tumours. The relatively high frequency of RASSF1A, DCR1, DCR2 and APC
      promoter methylation may imply that methylation constitutes an important pathway
      in the tumourigenesis of BCC that could provide new opportunities in developing
      epigenetic therapies for BCC patients. Nevertheless, further studies are needed
      to establish the above-mentioned hypothesis.

PMID- 24573470
TI  - Protein structure modeling with MODELLER.
AB  - Genome sequencing projects have resulted in a rapid increase in the number of
      known protein sequences. In contrast, only about one-hundredth of these sequences
      have been characterized at atomic resolution using experimental structure
      determination methods. Computational protein structure modeling techniques have
      the potential to bridge this sequence-structure gap. In this chapter, we present
      an example that illustrates the use of MODELLER to construct a comparative model
      for a protein with unknown structure. Automation of a similar protocol has
      resulted in models of useful accuracy for domains in more than half of all known
      protein sequences. 

PMID- 24573471
TI  - RaptorX server: a resource for template-based protein structure modeling.
AB  - Assigning functional properties to a newly discovered protein is a key challenge
      in modern biology. To this end, computational modeling of the three-dimensional
      atomic arrangement of the amino acid chain is often crucial in determining the
      role of the protein in biological processes. We present a community-wide web
      based protocol, RaptorX server ( http://raptorx.uchicago.edu ), for automated
      protein secondary structure prediction, template-based tertiary structure
      modeling, and probabilistic alignment sampling.Given a target sequence, RaptorX
      server is able to detect even remotely related template sequences by means of a
      novel nonlinear context-specific alignment potential and probabilistic
      consistency algorithm. Using the protocol presented here it is thus possible to
      obtain high-quality structural models for many target protein sequences when only
      distantly related protein domains have experimentally solved structures. At
      present, RaptorX server can perform secondary and tertiary structure prediction
      of a 200 amino acid target sequence in approximately 30 min.

PMID- 24573472
TI  - The MULTICOM protein tertiary structure prediction system.
AB  - With the expansion of genomics and proteomics data aided by the rapid progress of
      next-generation sequencing technologies, computational prediction of protein
      three-dimensional structure is an essential part of modern structural genomics
      initiatives. Prediction of protein structure through understanding of the
      theories behind protein sequence-structure relationship, however, remains one of
      the most challenging problems in contemporary life sciences. Here, we describe
      MULTICOM, a multi-level combination technique, intended to predict moderate- to
      high-resolution structure of a protein through a novel approach of combining
      multiple sources of complementary information derived from the experimentally
      solved protein structures in the Protein Data Bank. The MULTICOM web server is
      freely available at http://sysbio.rnet.missouri.edu/multicom_toolbox/.

PMID- 24573473
TI  - Modeling of protein side-chain conformations with RASP.
AB  - Modeling of side-chain conformations on a fixed protein backbone, also called
      side-chain packing, plays an important role in protein structure prediction,
      protein design, molecular docking, and functional analysis. RASP, or RApid Side
      chain Predictor, is a recently developed program that can model protein side
      chain conformations with both high accuracy and high speed. Moreover, it can
      generate structures with few atomic clashes. This chapter first provides a brief
      introduction to the principle and performances of the RASP package. Then details
      on how to use RASP programs to predict protein side-chain conformations are
      elaborated. Finally, it describes case studies for structure refinement in
      homology modeling and residue substitution. 

PMID- 24573474
TI  - Direct coupling analysis for protein contact prediction.
AB  - During evolution, structure, and function of proteins are remarkably conserved,
      whereas amino-acid sequences vary strongly between homologous proteins.
      Structural conservation constrains sequence variability and forces different
      residues to coevolve, i.e., to show correlated patterns of amino-acid
      occurrences. However, residue correlation may result from direct coupling, e.g.,
      by a contact in the folded protein, or be induced indirectly via intermediate
      residues. To use empirically observed correlations for predicting residue-residue
      contacts, direct and indirect effects have to be disentangled. Here we present
      mechanistic details on how to achieve this using a methodology called Direct
      Coupling Analysis (DCA). DCA has been shown to produce highly accurate estimates
      of amino-acid pairs that have direct reciprocal constraints in evolution.
      Specifically, we provide instructions and protocols on how to use the algorithmic
      implementations of DCA starting from data extraction to predicted-contact
      visualization in contact maps or representative protein structures. 

PMID- 24573475
TI  - ITScorePro: an efficient scoring program for evaluating the energy scores of
      protein structures for structure prediction.
AB  - One important component in protein structure prediction is to evaluate the free
      energy of a given conformation. Given the enormous number of possible
      conformations for a sequence, it is extremely challenging to quickly and
      accurately score the energies of these conformations and predict a reasonable
      structure within a practical computational time. Here, we describe an efficient
      program for energy evaluation, referred to as ITScorePro (Copyright (c) 2012).
      The energy scoring function in the ITScorePro program is based on the distance
      dependent, pairwise atomic potentials for protein structure prediction that we
      recently derived by using statistical mechanics principles (Huang and Zou,
      Proteins 79:2648-2661, 2011). ITScorePro is a stand-alone program and can also be
      easily implemented in other software suites for protein structure prediction.

PMID- 24573476
TI  - Assessing the quality of modelled 3D protein structures using the ModFOLD server.
AB  - Model quality assessment programs (MQAPs) aim to assess the quality of modelled
      3D protein structures. The provision of quality scores, describing both global
      and local (per-residue) accuracy are extremely important, as without quality
      scores we are unable to determine the usefulness of a 3D model for further
      computational and experimental wet lab studies.Here, we briefly discuss protein
      tertiary structure prediction, along with the biennial Critical Assessment of
      Techniques for Protein Structure Prediction (CASP) competition and their key role
      in driving the field of protein model quality assessment methods (MQAPs). We also
      briefly discuss the top MQAPs from the previous CASP competitions. Additionally,
      we describe our downloadable and webserver-based model quality assessment
      methods: ModFOLD3, ModFOLDclust, ModFOLDclustQ, ModFOLDclust2, and IntFOLD-QA. We
      provide a practical step-by-step guide on using our downloadable and webserver
      based tools and include examples of their application for improving tertiary
      structure prediction, ligand binding site residue prediction, and oligomer
      predictions.

PMID- 24573477
TI  - 3D-SURFER 2.0: web platform for real-time search and characterization of protein
      surfaces.
AB  - The increasing number of uncharacterized protein structures necessitates the
      development of computational approaches for function annotation using the protein
      tertiary structures. Protein structure database search is the basis of any
      structure-based functional elucidation of proteins. 3D-SURFER is a web platform
      for real-time protein surface comparison of a given protein structure against the
      entire PDB using 3D Zernike descriptors. It can smoothly navigate the protein
      structure space in real-time from one query structure to another. A major new
      feature of Release 2.0 is the ability to compare the protein surface of a single
      chain, a single domain, or a single complex against databases of protein chains,
      domains, complexes, or a combination of all three in the latest PDB.
      Additionally, two types of protein structures can now be compared: all-atom
      surface and backbone-atom-surface. The server can also accept a batch job for a
      large number of database searches. Pockets in protein surfaces can be identified
      by VisGrid and LIGSITE (csc) . The server is available at http://kiharalab.org/3d
      surfer/.

PMID- 24573479
TI  - POODLE: tools predicting intrinsically disordered regions of amino acid sequence.
AB  - Protein intrinsic disorder, a widespread phenomenon characterized by a lack of
      stable three-dimensional structure, is thought to play an important role in
      protein function. In the last decade, dozens of computational methods for
      predicting intrinsic disorder from amino acid sequences have been developed. They
      are widely used by structural biologists not only for analyzing the biological
      function of intrinsic disorder but also for finding flexible regions that
      possibly hinder successful crystallization of the full-length protein. In this
      chapter, I introduce Prediction Of Order and Disorder by machine LEarning
      (POODLE), which is a series of programs accurately predicting intrinsic disorder.
      After giving the theoretical background for predicting intrinsic disorder, I give
      a detailed guide to using POODLE. I then also briefly introduce a case study
      where using POODLE for functional analyses of protein disorder led to a novel
      biological findings. 

PMID- 24573478
TI  - SPOT-Seq-RNA: predicting protein-RNA complex structure and RNA-binding function
      by fold recognition and binding affinity prediction.
AB  - RNA-binding proteins (RBPs) play key roles in RNA metabolism and post
      transcriptional regulation. Computational methods have been developed separately
      for prediction of RBPs and RNA-binding residues by machine-learning techniques
      and prediction of protein-RNA complex structures by rigid or semiflexible
      structure-to-structure docking. Here, we describe a template-based technique
      called SPOT-Seq-RNA that integrates prediction of RBPs, RNA-binding residues, and
      protein-RNA complex structures into a single package. This integration is
      achieved by combining template-based structure-prediction software, SPARKS X,
      with binding affinity prediction software, DRNA. This tool yields reasonable
      sensitivity (46 %) and high precision (84 %) for an independent test set of 215
      RBPs and 5,766 non-RBPs. SPOT-Seq-RNA is computationally efficient for genome
      scale prediction of RBPs and protein-RNA complex structures. Its application to
      human genome study has revealed a similar sensitivity and ability to uncover
      hundreds of novel RBPs beyond simple homology. The online server and downloadable
      version of SPOT-Seq-RNA are available at http://sparks-lab.org/server/SPOT-Seq
      RNA/.

PMID- 24573480
TI  - Prediction of intrinsic disorder in proteins using MFDp2.
AB  - Intrinsically disordered proteins (IDPs) are either entirely disordered or
      contain disordered regions in their native state. IDPs were found to be abundant
      across all kingdoms of life, particularly in eukaryotes, and are implicated in
      numerous cellular processes. Experimental annotation of disorder lags behind the
      rapidly growing sizes of the protein databases and thus computational methods are
      used to close this gap and to investigate the disorder. MFDp2 is a novel
      webserver for accurate sequence-based prediction of protein disorder which also
      outputs well-described sequence-derived information that allows profiling the
      predicted disorder. We conveniently visualize sequence conservation, predicted
      secondary structure, relative solvent accessibility, and alignments to chains
      with annotated disorder. The webserver allows predictions for multiple proteins
      at the same time, includes help pages and tutorial, and the results can be
      downloaded as text-based (parsable) file. MFDp2 is freely available at
      http://biomine.ece.ualberta.ca/MFDp2/.

PMID- 24573481
TI  - Modeling protein-protein complexes using the HADDOCK webserver "modeling protein
      complexes with HADDOCK".
AB  - Protein-protein interactions lie at the heart of most cellular processes.
      Determining their high-resolution structures by experimental methods is a
      nontrivial task, which is why complementary computational approaches have been
      developed over the years. To gain structural and dynamical insight on an atomic
      scale in these interactions, computational modeling must often be complemented by
      low-resolution experimental information. For this purpose, we developed the user
      friendly HADDOCK webserver, the interface to our biomolecular docking program,
      which can make use of a variety of low-resolution data to drive the docking
      process. In this chapter, we explain the use of the HADDOCK webserver based on
      the real-life Lys48-linked di-ubiquitin case, which led to the 2BGF PDB model. We
      demonstrate the use of chemical shift perturbation data in combination with
      residual dipolar couplings and further highlight a few other cases where our
      software was successfully used. The HADDOCK webserver is available to the science
      community for free at haddock.science.uu.nl/services/HADDOCK.

PMID- 24573482
TI  - Predicting the structure of protein-protein complexes using the SwarmDock Web
      Server.
AB  - Protein-protein interactions drive many of the biological functions of the cell.
      Any two proteins have the potential to interact; however, whether the
      interactions are of biological significance is dependent on a number of
      complicated factors. Thus, modelling the three-dimensional structure of protein
      protein complexes is still considered to be a complex endeavor. Nevertheless,
      many experimentalists now wish to boost their knowledge of protein-protein
      interactions, well beyond complexes resolved experimentally, and for them to be
      able to do so it is important they are able to effectively and confidently
      predict protein-protein interactions. The main aim of this chapter is to acquaint
      the reader, particularly one from a non-computational background, how to use a
      state-of-the-art protein docking tool. In particular, we describe here the
      SwarmDock Server (SDS), a web service for the flexible modelling of protein
      protein complexes; this server is freely available at:
      http://bmm.cancerresearchuk.org/~SwarmDock/. Supplementary files for Case Studies
      are provided with the chapter and available at extras.springer.com.

PMID- 24573483
TI  - DOCK/PIERR: web server for structure prediction of protein-protein complexes.
AB  - In protein docking we aim to find the structure of the complex formed when two
      proteins interact. Protein-protein interactions are crucial for cell function.
      Here we discuss the usage of DOCK/PIERR. In DOCK/PIERR, a uniformly discrete
      sampling of orientations of one protein with respect to the other, are scored,
      followed by clustering, refinement, and reranking of structures. The novelty of
      this method lies in the scoring functions used. These are obtained by examining
      hundreds of millions of correctly and incorrectly docked structures, using an
      algorithm based on mathematical programming, with provable convergence
      properties.

PMID- 24573484
TI  - Pairwise and multimeric protein-protein docking using the LZerD program suite.
AB  - Physical interactions between proteins are involved in many important cell
      functions and are key for understanding the mechanisms of biological processes.
      Protein-protein docking programs provide a means to computationally construct
      three-dimensional (3D) models of a protein complex structure from its component
      protein units. A protein docking program takes two or more individual 3D protein
      structures, which are either experimentally solved or computationally modeled,
      and outputs a series of probable complex structures.In this chapter we present
      the LZerD protein docking suite, which includes programs for pairwise docking,
      LZerD and PI-LZerD, and multiple protein docking, Multi-LZerD, developed by our
      group. PI-LZerD takes protein docking interface residues as additional input
      information. The methods use a combination of shape-based protein surface
      features as well as physics-based scoring terms to generate protein complex
      models. The programs are provided as stand-alone programs and can be downloaded
      from http://kiharalab.org/proteindocking.

PMID- 24573485
TI  - Protocols for efficient simulations of long-time protein dynamics using coarse
      grained CABS model.
AB  - Coarse-grained (CG) modeling is a well-acknowledged simulation approach for
      getting insight into long-time scale protein folding events at reasonable
      computational cost. Depending on the design of a CG model, the simulation
      protocols vary from highly case-specific-requiring user-defined assumptions about
      the folding scenario-to more sophisticated blind prediction methods for which
      only a protein sequence is required. Here we describe the framework protocol for
      the simulations of long-term dynamics of globular proteins, with the use of the
      CABS CG protein model and sequence data. The simulations can start from a random
      or a selected (e.g., native) structure. The described protocol has been validated
      using experimental data for protein folding model systems-the prediction results
      agreed well with the experimental results. 

PMID- 24573486
TI  - Identification of peptides that bind hepatitis C virus envelope protein E2 and
      inhibit viral cellular entry from a phage-display peptide library.
AB  - Hepatitis C virus (HCV) envelope protein E2 is required for the entry of HCV into
      cells. Viral envelope proteins interact with cell receptors in a multistep
      process, which may be a promising target for the development of novel antiviral
      agents. In this study, a heptapeptide M13 phage-display library was screened for
      peptides that bind specifically to prokaryotically expressed, purified truncated
      HCV envelope protein E2. ELISA assay was used to quantify the binding of the
      peptides to HCV E2 protein. Flow cytometry, quantitative reverse-transcription
      PCR and western blotting were used to investigate the inhibition effect of one
      peptide on HCV infection in hepatoma cells (Huh7.5) in vitro. Four peptides
      capable of binding specifically to HCV E2 protein were obtained after three
      rounds of biopanning. Peptide C18 (WPWHNHR), with the highest affinity for
      binding HCV E2 protein, was synthesized. The results showed that peptide C18
      inhibited the viral infectivity of both HCV pseudotype particles (HCVpp)
      harboring HCV envelope glycoproteins and cell-culture produced HCV (HCVcc). Thus,
      this study demonstrated that peptide C18 is a potential candidate for anti-HCV
      therapy as a novel viral entry inhibitor.

PMID- 24573487
TI  - Anti-proliferative effects of quercetin and catechin metabolites.
AB  - Dietary flavonoids have been associated with a lower incidence of some chronic
      diseases. However, the mechanisms behind the in vivo biological activity of
      flavonoids are still mostly unknown. Flavonoids are metabolized in the human body
      to conjugated forms (methylated, sulphated and glucuronidated derivatives) that
      should play a role in flavonoid activity. In this study, the anti-proliferative
      effects of conjugated metabolites of quercetin and (epi)catechin, major
      flavonoids in the diet, have been evaluated against three different cancer cell
      lines from breast (MCF-7), colon (Caco-2) and pancreas (BxPC-3) and one normal
      cell line of human foreskin fibroblasts (HFF-1), and compared with the effect of
      their unconjugated forms. Quercetin showed anti-proliferative activity on the
      three assayed cell models, whereas catechin and epicatechin were not active.
      Methylation on ring-B of quercetin decreased the anti-proliferative effects,
      especially when the methylation occurred in position 3' (isorhamnetin), although
      methylated metabolites still showed significant anti-proliferative activity. As
      to catechins, 4'-O-methyl-epicatechin and 3'-O-methyl-epicatechin were the only
      ones to show some activity on MCF-7 and BxPC-3 cell lines, respectively.
      Conjugation of quercetin with glucose or glucuronic acid eliminated the anti
      proliferative effects of aglycones. Sulphated metabolites were also tested and
      found to be inactive in most of the explored cell lines, although quercetin-4'-O
      sulphate and epicatechin-3'-O-sulphate still showed some anti-proliferative
      activity on MCF-7 and Caco-2 cells, respectively.

PMID- 24573489
TI  - miR-7 inhibits the invasion and metastasis of gastric cancer cells by suppressing
      epidermal growth factor receptor expression.
AB  - The present study profiled differentially expressed microRNAs (miRs) in gastric
      cancer cell lines and then investigated miR-7 expression in gastric cancer tissue
      specimens and the effects of miR-7 on the growth, invasion and metastasis of
      gastric cancer cells and the underlying molecular events. A microRNA microarray
      was used to profile differentially expressed miRNAs in human gastric cancer cell
      lines relative to a normal stomach mucosal epithelial cell line. The miRNA miR-7
      was selected for further investigation, which included real-time reverse
      transcription PCR (qRT-PCR) analysis of miR-7 levels in different gastric cancer
      cell lines and tissues and distant non-tumor tissues from patient resections.
      Cell counting kit-8 (CCK-8), Transwell migration and invasion, and western blot
      assays were performed to assess tumor cell viability, invasion and gene
      expression, respectively, after miR-7 transfection. The miRNA microarray
      profiling revealed 14 upregulated miRNAs (including miR-21, miR-26b and miR-30b)
      and 19 downregulated miRNAs (including let-7i, miR-7 and miR-622) between gastric
      cancer and normal cell lines. The qRT-PCR analysis confirmed that reduced miR-7
      expression occurred more frequently in poorly and moderately differentiated
      gastric cancer MGC-803, MKN-45 and SGC-7901 cell lines than in the well
      differentiated gastric cancer NCI-N87 cell line, which was consistent with the
      results for gastric cancer tissues. Expression of miR-7 was downregulated in
      86.9% (20/23) of the gastric cancer tissues compared with that in the distant non
      tumor tissues. Restoration of miR-7 expression significantly inhibited tumor cell
      viability, invasiveness and migration when compared with the control cells.
      Luciferase assay confirmed the epidermal growth factor receptor (EGFR) as a
      target gene of mR-7, and expression of miR-7 significantly suppressed EGFR
      expression at both the mRNA and protein levels. The data from the present study
      demonstrated that reduced miR-7 expression contributes to gastric cancer
      development and progression. Further study will investigate miR-7 in the
      regulation of EGFR expression in vitro and in vivo.

PMID- 24573490
TI  - Kelp use in patients with thyroid cancer.
AB  - To report on the incidence and use of kelp among patients with thyroid cancer.
      Data were collected using a web-based online anonymous survey under Institutional
      Review Board approval from Boston University. This report is based on 27
      responses from subjects with thyroid cancer who use kelp. Demographic factors and
      complementary and alternative use were included. Respondents were primarily over
      age 40, white, female and have at least a high school education. The top five
      modalities were multivitamins, special diets, herbal supplements, prayer for
      health reasons and herbal tea. Only one patient reported perceiving a particular
      modality had a negative effect on treatment. Complementary and alternative
      medicine (CAM) was more often perceived as being used to aid their thyroid cancer
      treatment than to help with symptoms. On average, respondents who use kelp also
      use at least 11 additional CAM modalities. Only 1/2 of respondents who use kelp
      reported telling their physicians about their CAM use, and nearly 1/3 of
      respondents reported their CAM use was neither known, prescribed nor asked about
      by their physicians. In comparison to both national surveys of the general US
      population and patients with thyroid cancer, kelp users with thyroid cancer use
      at least twice the number of additional CAM therapies and report their use far
      less often. Physicians who treat patients with thyroid cancer should be aware of
      these data to further assist in their assessment and care. 

PMID- 24573492
TI  - C242T polymorphism of the NADPH oxidase p22PHOX gene and its association with
      endothelial dysfunction in asymptomatic individuals with essential systemic
      hypertension.
AB  - Vascular oxidative stress is an important factor in hypertension-associated
      vascular damage and is mediated by nicotinamide adenine dinucleotide phosphate
      (NADPH) oxidase activation. The C242T polymorphism at the p22PHOX gene affects
      binding of p22PHOX to heme, leading to variants of NADPH oxidase that produce
      different levels of reactive oxygen species (ROS). Specific variations in ROS are
      associated with an altered risk of developing cardiovascular disease. In the
      present study, 140 permanent Kashmiri-resident individuals were recruited (75
      with essential systemic hypertension and 65 normotensive controls). Endothelial
      function was assessed non-invasively using high-resolution ultrasonography of the
      brachial artery. Endothelium-dependent vasoreactivity was expressed in terms of
      flow-mediated dilation. The TT genotype was identified in 2% of hypertensive and
      7% of normotensive individuals. Frequency of the T-allele was not observed as
      significantly different between hypertensive and normotensive individuals
      (P=0.24; OR=0.4; 95% CI, 0.07-2.2). Blood pressure or the prevalence of
      hypertension did not vary between C242T p22PHOX genotypes or in the presence or
      absence of the T-allele.

PMID- 24573493
TI  - Warping effect-induced optical absorbance increment of topological insulator
      films for THz photodetectors with high signal-to-noise ratio.
AB  - Strong optical absorbance makes topological insulator (TI) surfaces a promising
      high-performance photodetector in the terahertz (THz) to infrared frequency
      range. Here, we study the optical absorbance of more realistic TI films with
      hexagonal warping effect using the Fermi's golden rules. It was found that when
      the warping term is lambda ? 0, the absorbance is no longer a universal value as
      that of graphene or ideal Dirac cone, but increases monotonously with the photon
      energy. The increment is positively correlated with the parameter lambda/vF(3)
      where vF is the Fermi velocity. The relative signal-to-noise ratio (SNR) of the
      TI film working as a photoresistor-type photodetector is significantly enhanced
      by the warping effect-induced absorbance increment. These investigations provide
      useful information for developing TI-based photodetectors with high SNR in the
      range of THz to infrared frequency. 

PMID- 24573491
TI  - Sustained high levels of serum leptin rather than IL-6 observed in patients with
      postpartum thyroiditis during their first postpartum year.
AB  - The purpose of the study is to explore the roles of leptin and interleukin-6 (IL
      6) during the first postpartum year in the occurrence and development of
      postpartum thyroiditis (PPT). We retrospectively collected serum samples from 57
      PPT patients consisting of 34 overt PPT (O-PPT) and 23 subclinical PPT (S-PPT) in
      addition to 37 healthy postpartum women at four postpartum time points, i.e., 3
      day and 3, 6, 12-month postpartum. Serum leptin and IL-6 levels were measured by
      radioimmunoassay and ELISA assay, respectively. Leptin level and leptin/BMI
      (LEP/BMI) ratio were higher in PPT patients than in control during the first
      postpartum year, but were not significantly different between O-PPT and S-PPT.
      However, a similar trend but did not reach significant difference in IL-6 level
      was observed during the postpartum period in PPT patients and control women. We
      conclude that a sustained high level of serum leptin after delivery may be
      involved in the pathogenesis of PPT. IL-6 does not contribute to the development
      of PPT. 

PMID- 24573488
TI  - The multiple faces of leukocyte interstitial migration.
AB  - Spatiotemporal control of leukocyte dynamics within tissues is critical for
      successful innate and adaptive immune responses. Homeostatic trafficking and
      coordinated infiltration into and within sites of inflammation and infection rely
      on signaling in response to extracellular cues that in turn controls a variety of
      intracellular protein networks regulating leukocyte motility, migration,
      chemotaxis, positioning, and cell-cell interaction. In contrast to mesenchymal
      cells, leukocytes migrate in an amoeboid fashion by rapid cycles of actin
      polymerization and actomyosin contraction, and their migration in tissues is
      generally referred to as low adhesive and nonproteolytic. The interplay of actin
      network expansion, contraction, and adhesion shapes the exact mode of amoeboid
      migration, and in this review, we explore how leukocyte subsets potentially
      harness the same basic biomechanical mechanisms in a cell-type-specific manner.
      Most of our detailed understanding of these processes derives from in vitro
      migration studies in three-dimensional gels and confined spaces that mimic
      geometrical aspects of physiological tissues. We summarize these in vitro results
      and then critically compare them to data from intravital imaging of leukocyte
      interstitial migration in mouse tissues. We outline the technical challenges of
      obtaining conclusive mechanistic results from intravital studies, discuss
      leukocyte migration strategies in vivo, and present examples of mode switching
      during physiological interstitial migration. These findings are also placed in
      the context of leukocyte migration defects in primary immunodeficiencies. This
      overview of both in vitro and in vivo studies highlights recent progress in
      understanding the molecular and biophysical mechanisms that shape robust
      leukocyte migration responses in physiologically complex and heterogeneous
      environments. 

PMID- 24573494
TI  - Quantitative effects of leaf area removal on indirect defense of lima bean
      (Phaseolus lunatus) in nature.
AB  - Plants employ a diverse array of defensive traits against multiple enemies. While
      many plant defenses are well-studied, quantitative feedback effects of leaf area
      loss on the expression of defensive traits remain little understood. Extrafloral
      nectar (EFN; an indirect defense acting via the attraction of carnivorous
      arthropods) is generally considered 'cheap' as it is composed mainly of
      photosynthates. However, to what extent EFN secretion is related to the amount of
      intact photosynthetic leaf area is unknown. In this study, we measured the
      production of EFN, ant attraction, and herbivore damage in response to a gradient
      of leaf area removal in wild lima bean (Phaseolus lunatus) under natural
      conditions in southern Mexico. EFN production and ant recruitment were
      significantly decreased with increasing leaf area removal. Consequently, EFN
      production was inversely correlated with leaf area loss, which suggests that EFN
      is metabolically more expensive than previously thought. Further, we found
      increased herbivory in plants with reduced EFN secretion indicating additive
      negative feedback effects of leaf area loss. Our study is one of the first
      showing a quantitative negative impact of leaf damage on EFN secretion-one of the
      most widely distributed defensive traits in the plant kingdom.

PMID- 24573496
TI  - Different proton transfer channels for the transformation of zwitterionic alanine
      (H2O)(n=2-4) to nonzwitterionic alanine-(H2O)(n=2-4): a density functional theory
      study.
AB  - We report here the various possibilities of proton transfer between the
      zwitterionic and the non-zwetterionic form of alanine (Ala) via (H2O)(n=2-4)
      clusters by calculating the transition state structures of zwitterionic alanine
      (ZAla)-(H2O)(n=2-4) and non-zwitterionic alanine (Ala)-(H2O)(n=2-4) complexes at
      B3LYP/6-311++G(d,p) and CAM-B3LYP/6-311++G(d,p) level of theory. In order to
      determine the most feasible channel for proton transfer, the barrier energy
      corresponding to each channel was calculated. For the transformation of ZAla
      (H2O)(n=2) to Ala-(H2O)(n=2), we identified eight channels for proton transfer.
      The lowest barrier energy (2.57 kcal mol-1) channel, where ZAla-(H2O)(n=2)
      transforms to Ala-(H2O)(n=2) via triple proton transfer, is said to be the
      energetically most feasible channel. The values of barrier energy corresponding
      to the least energy pathway for proton transfer were calculated to be 1.14 and
      9.82 kcal mol-1 for n = 3 and n = 4 complexes, respectively, at B3LYP/6
      311++G(d,p) level of theory. For complex n = 3, the structure where proton
      transfer takes place directly from -NH3+ to -COO- has the lowest energy pathway.
      However, the complexes for n = 2 and 3--the channels where proton transferred
      from -NH3+ to -COO- via two water molecules have the lowest barrier energy. For
      each n, the values of barrier energy calculated at CAM-B3LYP/6-311++G(d,p) level
      of theory were always less compared those calculated at B3LYP/6-311++G(d,p) level
      of theory. The value of rate constants corresponding to each proton transfer
      channel was also calculated.

PMID- 24573497
TI  - Reaction mechanism of methylamine decomposition on Ru(0001): a density functional
      theory study.
AB  - The reaction mechanism of methylamine decomposition on Ru(0001) has been
      systematically investigated by density functional theory slab calculations. The
      decomposition network has also been described. The adsorption energies under the
      most stable configuration of the possible species and the energy barriers of the
      possible elementary reactions involved are obtained. Desorption is preferred for
      adsorbing methylamine and hydrogen, whereas for the other species, decomposition
      is more favorable. Our calculated results show that methylamine decomposition on
      Ru(0001) starts with H2CNH2 formation from methyl dehydrogenation, followed by
      subsequent methylene dehydrogenation, bond breaking of N--H and C--N in HCNH2, CH
      dehydrogenation and C-N bond cleavage in HCNH, and dehydrogenation of NH2, NH,
      and CH.

PMID- 24573498
TI  - Density functional theory and molecular dynamics study of the uranyl ion (UO2)2+.
AB  - The detection of uranium is very important, especially in water and, more
      importantly, in the form of uranyl ion (UO2)2+, which is one of its most abundant
      moieties. Here, we report analyses and simulations of uranyl in water using ab
      initio modified force fields for water with improved parameters and charges of
      uranyl. We use a TIP4P model, which allows us to obtain accurate water properties
      such as the boiling point and the second and third shells of water molecules in
      the radial distribution function thanks to a fictitious charge that corrects the
      3-point models by reproducing the exact dipole moment of the water molecule. We
      also introduced non-bonded interaction parameters for the water-uranyl
      intermolecular force field. Special care was taken in testing the effect of a
      range of uranyl charges on the structure of uranyl-water complexes. Atomic
      charges of the solvated ion in water were obtained using density functional
      theory (DFT) calculations taking into account the presence of nitrate ions in the
      solution, forming a neutral ensemble. DFT-based force fields were calculated in
      such a way that water properties, such as the boiling point or the pair
      distribution function stand. Finally, molecular dynamics simulations of a water
      box containing uranyl cations and nitrate anions are performed at room
      temperature. The three peaks in the oxygen-oxygen radial distribution function
      for water were found to be kept in the presence of uranyl thanks to the
      improvement of interaction parameters and charges. Also, we found three shells of
      water molecules surrounding the uranyl ion instead of two as was previously
      thought.

PMID- 24573499
TI  - A density functional theory study of paramagnetic cyclopentadienylcobalt(III)
      derivatives: fluoride versus cyanide.
AB  - The cobalt(III) complexes Cp2Co2F4 and Cp2Co2(CN)4 have been studied by density
      functional theory methods as representatives of the experimentally known Cp2Co2X4
      species with the weak-field fluoride ligand and the strong-field cyanide ligand.
      Both complexes were found to have relatively complicated energy surfaces with low
      energy triplet and quintet spin state structures as well as the expected singlet
      state structures for Co(III) complexes. This existence of singlet-, triplet-, and
      quintet-state structures of similar energies complicates the study of these
      complexes by density functional theory. The B3LYP* method of Reiher et al. was
      chosen in an effort to provide the most reliable estimates of the relative
      energies of the singlet, triplet, and quintet spin states. The lowest-energy
      Cp2Co2F4 structure was found to be a doubly bridged quintet spin state structure,
      with similar triplet and singlet structures lying within ~4 kcal mol-1 of this
      quintet structure. The lowest-energy Cp2Co2(CN)4 structure was found to be a
      triplet spin state structure, with a singlet structure lying within ~1 kcal mol-1
      of this triplet structure. Almost all of the Cp2Co2X4 structures were found to
      have nonbonding Co...Co distances in excess of 2.9 A, as expected for Co(III)
      complexes. In general, structures with trans stereochemistry of the Cp and other
      terminal ligands were found to be of lower energy than the corresponding
      structures with cis stereochemistry.

PMID- 24573500
TI  - Self-consistent field convergence for proteins: a comparison of full and
      localized-molecular-orbital schemes.
AB  - Proteins in the gas phase present an extreme (and unrealistic) challenge for self
      consistent-field iteration schemes because their ionized groups are very strong
      electron donors or acceptors, depending on their formal charge. This means that
      gas-phase proteins have a very small band gap but that their frontier orbitals
      are localized compared to "normal" conjugated semiconductors. The frontier
      orbitals are thus likely to be separated in space so that they are close to, but
      not quite, orthogonal during the SCF iterations. We report full SCF calculations
      using the massively parallel EMPIRE code and linear scaling localized-molecular
      orbital (LMO) calculations using Mopac2009. The LMO procedure can lead to
      artificially over-polarized wavefunctions in gas-phase proteins. The full SCF
      iteration procedure can be very slow to converge because many cycles are needed
      to overcome the over-polarization by inductive charge shifts. Example molecules
      have been constructed to demonstrate this behavior. The two approaches give
      identical results if solvent effects are included. 

PMID- 24573502
TI  - Miniaturized fiber-optic ultrasound probes for endoscopic tissue analysis by
      micro-opto-mechanical technology.
AB  - A new Micro-Opto-Mechanical System (MOMS) technology for the fabrication of
      optoacoustic probes on optical fiber is presented. The technology is based on the
      thermoelastic emission of ultrasonic waves from patterned carbon films for
      generation and on extrinsic polymer Fabry-Perot acousto-optical transducers for
      detection, both fabricated on miniaturized single-crystal silicon frames used to
      mount the ultrasonic transducers on the tip of an optical fiber. Thanks to the
      fabrication process adopted, high miniaturization levels are reached in the MOMS
      devices, demonstrating fiber-optic emitters and detectors with minimum diameter
      around 350 and 250 MUm respectively. A thorough functional testing of the
      ultrasound emitters mounted on 200 and 600 MUm diameter optical fibers is
      presented, in which the fiber-optic emitter with a diameter of 200 MUm shows
      generated acoustic pressures with peak-to-peak value up to 2.8 MPa with rather
      flat emission spectra extended beyond 150 MHz. The possibility to use the
      presented optoacoustic sources in conjunction with the fiber-optic acousto
      optical detectors within a minimally invasive probe is also demonstrated by
      successfully measuring the ultrasonic echo reflected from a rigid surface
      immersed in water with various concentration of scatterers. The resulting spectra
      highlight the possibility to discriminate the effects due to frequency selective
      attenuation in a very wide range of frequencies within a biological medium using
      the presented fiber-optic probes.

PMID- 24573501
TI  - In pursuit of negative Fukui functions: molecules with very small band gaps.
AB  - A justification for the likely presence of negative Fukui functions in molecules
      with small band gaps is given, and a computational study performed to check
      whether molecules with small band gaps have negative Fukui functions to a
      chemically significant extent is reported. While regions with negative Fukui
      functions were observed, significantly negative values for the atom-condensed
      Fukui functions were not observed. 

PMID- 24573503
TI  - Electrical impedance tomographic imaging of a single cell electroporation.
AB  - A living cell placed in a high strength electric field, can undergo a process
      known as electroporation. It is believed that during electroporation nano-scale
      defects (pores) occur in the membrane of the cell, causing dramatic changes to
      the permeability of its membrane. Electroporation is an important technique in
      biotechnology and medicine and numerous methods are being developed to improve
      the understanding and use of the technology. We propose to extend the toolbox
      available for studying electroporation by generating impedance distribution
      images of the cell as it undergoes electroporation using Electrical Impedance
      Tomography (EIT). To investigate the feasibility of this concept, we develop a
      mathematical model of the process of electroporation in a single cell and of EIT
      of the process and show simulation results of a computer-based finite element
      model (FEM). Our work is an attempt to develop a new imaging tool for visualizing
      electroporation in a single cell, offering a different temporal and spatial
      resolution compared to the state of the art, which includes bulk measurements of
      electrical properties during single cell electroporation, patch clamp and voltage
      clamp measurement in single cells and optical imaging with colorimetric dyes
      during single cell electroporation. This paper is a preliminary theoretic
      feasibility study. 

PMID- 24573504
TI  - Investigation of uterine arterial chemoembolization and uterine arterial infusion
      chemotherapy for advanced cervical cancer before radical radiotherapy: a long
      term follow-up study.
AB  - PURPOSE: To investigate the contribution of uterine arterial chemoembolization
      (UACE) and uterine arterial infusion chemotherapy (UAIC) to advanced cervical
      cancer before radical radiotherapy. METHODS: A total of 735 patients with primary
      advanced cervical cancer were retrospectively studied; of these patients, 299
      were classified as FIGO stage II, 359 as stage III and 77 as stage IVa. 126
      underwent UACE, 103 underwent UAIC before radiotherapy, and 506 received radical
      radiotherapy alone (RT). Disease-specific survival (DSS), pelvic control (PC),
      distant metastasis-free survival (MFS), and risk factors of late toxicity were
      analyzed. RESULTS: The 1-, 2-, 5-, and 8-year DSS of all patients was 94.4, 82.1,
      50.2, and 30.7 %, respectively. The DSS of the UACE group was 96.0, 83.4, 39.6,
      18.3 %; UAIC group was 95.6, 84.3, 59.6, 42.7 % and RT group was 93.7, 80.8,
      51.5, 31.5 % (chi (2) = 10.236, P = 0.006). The 1- and 2-year DSS of the UAIC and
      UACE groups was higher than those of the RT group (chi (2) = 2.510, P = 0.285;
      chi (2) = 2.822, P = 0.244). The 5- and 8-year DSS of the UACE group was
      obviously decreased (chi (2) = 14.962, P = 0.001; chi (2) = 14.043, P = 0.001).
      PC and MFS were highest in the UAIC group and lowest in the UACE group. The
      incidence of late radiation toxicity of the small intestine and rectosigmoid was
      similar. The bladder injury was highest in the UACE group (UACE:UAIC:RT =
      11.1:4.8:4.2 %, chi (2) = 9.579, P = 0.008). UACE is a risk factor for late
      radiation toxicity of the urinary bladder. CONCLUSIONS: The use of UAIC before
      radical radiotherapy could improve the treatment outcome and prognosis of
      patients with advanced cervical cancer, while the UACE would significantly
      decrease long-time survival. UACE is an important risk factor for late radiation
      toxicity.

PMID- 24573505
TI  - The assessment of the relationship between amniotic fluid matrix
      metalloproteinase-9 and zinc levels with adverse obstetric outcomes.
AB  - OBJECTIVE: To examine the relationship between the amniotic fluid MMP-9 and zinc
      levels during 16-19th gestational weeks and perinatal outcomes. METHOD: One
      hundred and seventeen singleton pregnancies that underwent genetic amniocentesis
      from January 2005 through November 2009 were evaluated. Subjects were divided
      into two main groups: a control group (group 1) (n: 74), and an adverse obstetric
      outcomes group (group 2) (n: 43). Group 2 consisted of the following: preterm
      birth group, gestational hypertension and preeclampsia group, gestational
      diabetes group, fetal growth restriction group, macrosomia group, and pregnancy
      loss group. MMP-9 and zinc (Zn) values in the amniocentesis materials sampled
      between the 16th and 19th gestational weeks were analyzed retrospectively in
      terms of perinatal outcomes. Any significant difference among the groups was
      assessed by unpaired samples t test and the Mann-Whitney U test. Statistical
      significance was defined as p < 0.05. RESULTS: A comparison among groups showed
      no significant difference in terms of Zn results between the group 1 and 2 (p =
      0.879). MMP-9 levels were significantly lower in both the preterm birth group (p
      = 0.043) and group 1 (p = 0.015). CONCLUSION: We found that the amniotic fluid
      MMP-9 levels of patients who delivered preterm were significantly lower between
      the 16th and 19th gestational weeks.

PMID- 24573506
TI  - IUD in first-trimester abortion: immediate intrauterine contraceptive devices
      insertion vs delayed insertion following the next menstruation bleeding.
AB  - PURPOSE: Approximately 21 days after an abortion, ovulation occurs in 50 % of
      women. Installation of an IUD directly after induced or spontaneous abortion
      offers immediate contraceptive protection. The purpose of the present study was
      to weigh up contraceptive safety and adverse reactions of IUD inserted directly
      after first-trimester abortion under general or paracervical anesthesia as
      against the fitting of IUD in the days of the next menstrual cycle without
      anesthesia. METHOD: During the period May 1987 to October 2010, 73 women (Group
      A) underwent an immediate post-abortion insertion IUD after a first-trimester
      spontaneous or induced abortion under general or local paracervical anesthesia
      and 69 participants (Group B) received IUD during the next menstrual cycle
      without anesthesia. Questionnaires were completed by all the women of the study
      with respect to the effects of IUD. The women were examined every 3 months for 1
      year after the fitting of the IUD in the out-patient department of the University
      Obstetrics Gynecological Department of Alexandroupolis, Democritus University of
      Thrace, Greece. RESULTS: The demographic characteristics of the women of the two
      groups were similar. The age of the women ranged between 19 and 44 years, while
      61.98 % were women with one or two children and 38.02 % were women with three or
      more children. During the first menstrual cycles, with the exception of vaginal
      hemorrhages (5 %) and adnexitis (1 %), no serious adverse reactions were noted.
      During the transvaginal ultrasonography checks in both groups, no observation was
      made of any dislocation of the IUD, except for two cases in the subgroup of those
      women with paracervical anesthesia and one case in the women of Group B. As
      concerns the questionnaire with regard to the women's subjective evaluation of
      IUD, satisfactory answers were given. CONCLUSIONS: There were no differences
      between the two groups either with respect to the security of the supplied
      contraceptive methods or to the development of side effects.

PMID- 24573507
TI  - Correcting haemoglobin cut-offs to define anaemia in high-altitude pregnant women
      in Peru reduces adverse perinatal outcomes.
AB  - PURPOSE: To determine if correction of cut-offs of haemoglobin levels to define
      anaemia at high altitudes affects rates of adverse perinatal outcomes. METHODS:
      Data were obtained from 161,909 mothers and newborns whose births occurred
      between 1,000 and 4,500 m above sea level (masl). Anaemia was defined with or
      without correction of haemoglobin (Hb) for altitude as Hb <11 g/dL. Correction of
      haemoglobin per altitude was performed according to guidelines from the World
      Health Organization. Rates of stillbirths and preterm births were also
      calculated. RESULTS: Stillbirth and preterm rates were significantly reduced in
      cases of anaemia calculated after correction of haemoglobin for altitude compared
      to values obtained without Hb correction. At high altitudes (3,000-4,500 masl),
      after Hb correction, the rate of stillbirths was reduced from 37.7 to 18.3 per
      1,000 live births (p < 0.01); similarly, preterm birth rates were reduced from
      13.1 to 8.76 % (p < 0.01). The odds ratios for stillbirths and for preterm births
      were also reduced after haemoglobin correction. CONCLUSION: At high altitude,
      correction of maternal haemoglobin should not be performed to assess the risks
      for preterm birth and stillbirth. In fact, using low altitude Hb cut-off is
      associated with predicting those at risk.

PMID- 24573508
TI  - Newly diagnosed adult-onset Still's disease with pure red cell aplasia in
      pregnancy.
AB  - BACKGROUND: Adult-onset Still's disease (AOSD) is a rare inflammatory disease of
      unknown etiology that can present for the first time during pregnancy. Pure red
      cell aplasia (PRCA) is another rare condition that seldom is in association with
      AOSD. Herein, we have reported a newly diagnosed case with AOSD and PRCA in a
      previously healthy pregnant woman. CASE DESCRIPTION: A 25-year-old primigravida
      lady presented with fever, malaise, and arthralgia at 26 weeks of gestation. She
      had an extensive evaluation that led to the diagnosis of AOSD. Preliminary blood
      tests displayed a severe anemia with hemoglobin 5.1 g/dL, leukocytosis (total
      white blood cells count of 26,000 MUL(-1)), normal mean corpuscular volume,
      normal mean corpuscular hemoglobin, normal platelet count, and a low reticulocyte
      count (0.2 %). The condition was diagnosed as AOSD associated with PRCA. She was
      treated with prednisolone and had immediate and dramatic improvement. CONCLUSION:
      AOSD and PRCA in pregnancy are rare conditions. The recognition of these clinical
      syndromes may lead to earlier diagnosis and thus prevent the expensive
      investigations. Both conditions have a dramatic improvement upon using
      corticosteroids therapy.

PMID- 24573510
TI  - Action of an extract from the seeds of Fraxinus excelsior L. on metabolic
      disorders in hypertensive and obese animal models.
AB  - Nuzhenide and GI3, the principal secoiridoids of an extract obtained from the
      seeds of Fraxinus excelsior L. (FXE), are believed to be the active compounds
      responsible for the previously reported hypoglycemic effects of this extract. In
      this study, the effects of FXE were studied in two animal models which are
      representative of metabolic disorders: spontaneously hypertensive rats (SHR) and
      obese Zucker rats. SHR were acutely treated (oral gavage) with different doses of
      FXE. In addition, SHR and Zucker rats were chronically fed (20 or 5 weeks,
      respectively) with standard chow supplemented with FXE. Acute treatment with FXE
      (200 mg per kg body weight) decreased systolic blood pressure as in the case with
      captopril (50 mg per kg body weight). Chronic treatment with FXE at 100 mg per kg
      body weight per day, a dose equivalent to that showing hypoglycemic activity in
      humans, resulted in a significant decrease in glycemia (-16.3%), triglyceridemia
      (-33.4%) and body weight (-8.1%) in Zucker rats as well as a significant decrease
      in SBP in SHR (-6.7%), with a concomitant improvement in endothelial function in
      both strains. The broad-ranging effects of FXE may be due to a unique
      compositional profile that could be useful to prevent the metabolic syndrome,
      characterized by obesity, insulin resistance, glucose intolerance,
      hypertriglyceridemia and elevated blood pressure.

PMID- 24573511
TI  - Gaps in translation from trials to practice: non-vitamin K antagonist oral
      anticoagulants (NOACs) for stroke prevention in atrial fibrillation.
AB  - Worldwide there is a tremendous need for affordable anticoagulants that do not
      require monitoring. The advent of the non-warfarin oral anticoagulant drugs
      represents a major advance for stroke prevention in atrial fibrillation (AF). The
      objectives of this review are to 1) identify gaps in our current knowledge
      regarding use of these single target anticoagulant drugs; 2) outline the
      potential implications of these gaps for clinical practice, and thereby, 3)
      highlight areas of research to further optimise their use for stroke prevention
      in AF. 

PMID- 24573512
TI  - RASSF1A promotes apoptosis and suppresses the proliferation of ovarian cancer
      cells.
AB  - As the most lethal gynecological malignancy, ovarian cancer has attracted much
      attention over the past few decades; however, the early detection of this
      malignancy has been largely unsuccessful. The aim of this study was to determine
      the effects of Ras-association domain family 1, isoform A (RASSF1A) on ovarian
      cancer and to elucidate the molecular mechanisms responsible for these effects.
      The expression of RASSF1A in different ovarian cancer cells was detected by
      quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The
      morphology, structure, apoptosis and proliferation of differently treated SKOV-3
      cells were then analyzed using a fluorescence microscope, transmission electron
      microscope, flow cytometer and by western blot analysis, respectively. Moreover,
      the GSE14407 affymetrix microarray data were downloaded from the Gene Expression
      Omnibus database and the expression of RASSF1A was quantified by Spotfire
      DecisionSite software. A RASSF1A related protein-protein interaction (PPI)
      network was then constructed using STRING and Cytoscape software. Finally, DAVID
      was utilized to perform KEGG pathway enrichment analysis of the network. RASSF1A
      was expressed in the HO8910, HO8910PM cells and the SKOV-3 cells transfected with
      RASSF1A, whereas it was absent in the other SKOV-3 cells and OVCAR-3 cells.
      Additionally, compared with the other SKOV-3 cells, the nucleus of SKOV-3 cells
      transfected with RASSF1A was vacuolated, apoptosis was increased, and the
      expression of cyclin D1 and survivin was decreased (P<0.05), and that of p27 and
      caspase-3 was increased (P<0.01). Additionally, 10 genes, including
      serine/threonine kinase (STK)3, STK4, Harvey rat sarcoma viral oncogene homolog
      (HRAS) and cell division cycle 20 (CDC20), were found to have close interactions
      with RASSF1A in the PPI network. Finally, a total of 8 enriched pathways, such as
      bladder cancer, non-small cell lung cancer and pathways in cancer were
      identified. To our knowledge, this is the first study to explore the biological
      functions and the underlying mechanisms of action of RASSF1A in the development
      of ovarian cancer. Our findings may provide a novel therapeutic target for
      ovarian cancer.

PMID- 24573513
TI  - The elephant in the room.

PMID- 24573514
TI  - Hospitalist involvement in family medicine residency training: A CERA study.
AB  - BACKGROUND AND OBJECTIVES: Little is known about the impact of hospitalists on
      family medicine residencies. We surveyed family medicine residency directors to
      assess attitudes about hospitalists and their involvement in residency teaching.
      METHODS: Questions were included in the 2012 Council of Academic Family Medicine
      Educational Research Alliance (CERA) survey of family medicine residency
      directors. Univariate statistics were used to describe programs, directors, and
      our questions on the use of hospitalists. Bivariate statistics were used to
      examine relationships between the use of hospitalists to teach and program
      characteristics. RESULTS: Forty-one percent (n=175) of residency directors
      completed the hospitalist section of the CERA survey. Sixty-six percent of
      residency programs were community based/university affiliated. The majority of
      directors who have, or are planning to develop, a hospitalist service currently
      use an internal medicine service (92.5%), followed by family medicine (39.1%),
      pediatrics (35.4%), OB/laborists (18.0%), and combined services (8.7%). The
      majority of programs with a hospitalist training track (or plans to develop one)
      indicated that this was for a family medicine service. Sixty percent of programs
      that have a hospitalist service involve hospitalists in teaching. Twenty percent
      of directors reported that hospitalists serve as family medicine faculty, and 63%
      viewed them as "good educators." However, 85% reported no reduction in inpatient
      teaching by family medicine faculty despite using hospitalist teaching services.
      CONCLUSIONS: Hospitalists have a significant educational role in family medicine
      resident training. Further research is needed to explore how hospitalists and
      family medicine faculty can collaborate to promote enhanced efficiency and
      effectiveness as residency teachers.

PMID- 24573515
TI  - The status of adult inpatient care by family physicians at US academic medical
      centers and affiliated teaching hospitals 2003 to 2012: the impact of the
      hospitalist movement.
AB  - BACKGROUND AND OBJECTIVES: Over the past 10--15 years, the number of hospitalists
      has grown from a few hundred to over 30,000, and hospitalists have assumed a
      greater proportion of the care of hospitalized patients. No existing studies
      report on the impact this movement has had on the characteristics of the hospital
      practice of family physicians in teaching hospitals. To explore this impact we
      examined the volume and scope of discharges by family physicians at teaching
      hospitals in 2003 and 2012, the most recent decade of hospitalist growth. We also
      compared the characteristics of family physicians' hospital practices in 2012
      with hospitalists in 2012 to assess for differences in hospital performance.
      METHODS: We used the University Health Consortium (UHC) Clinical Database to
      capture adult non-pregnancy-related inpatient discharges in US teaching hospitals
      by family physicians and hospitalists in 2003 and 2012. We calculated the
      proportion of inpatient discharges by specialty in all UCH hospitals; did a
      qualitative comparison of frequent discharge diagnoses; and analyzed length of
      stay, case mix index, 7- and 30-day readmission rates, and mortality by specialty
      using UHCs risk adjustment methodology. RESULTS: The proportion of all inpatient
      discharges by family physicians in UHC hospitals was stable between 2003 and 2012
      (2.7% versus 2.6%) though the volume increased. Over the same time, the
      proportion of discharges attributable to hospitalists increased (0.0% to 13.9%)
      with a concomitant decrease in proportion of discharges from general medicine
      (18.4% to 13.9%) and all other specialties (78.9% to 73.2%). Fourteen of the top
      20 discharge diagnoses by family physicians from UHC hospitals were the same
      between 2003 and 2012. Family physicians and hospitalists shared 17 of the top 20
      discharge diagnoses in 2012. Length of hospital stay was stable for family
      medicine across time and lower than that of hospitalists (4.5 versus 5.5 days;
      P<.001). Seven- and 30-day readmission rates for any cause were lower for
      hospitalists but there was no difference in either rate when limited to
      readmission for the same DRG. Hospitalists cared for a somewhat more complex
      patient mix. CONCLUSIONS: The growth of hospitalists has had little to no impact
      on the proportion of inpatient discharges in teaching hospitals by family
      physicians. Quality of care as judged by length of stay, mortality, and
      readmission rates was comparable between family physicians and hospitals in 2012.

PMID- 24573516
TI  - Underrepresented minority faculty in academic medicine: a systematic review of
      URM faculty development.
AB  - BACKGROUND AND OBJECTIVES: Retention and recruitment of minority faculty members
      continues to be a concern of medical schools because there is higher attrition
      and talent loss among this group. While much has been written, there has not been
      a systematic review published on this topic. This is the first study to use
      evidence-based medicine (EBM) criteria and apply it to this issue. METHODS: We
      searched MEDLINE, Web of Knowledge, ProQuest, and Google Scholar for papers
      relating to the recruitment and retention of minority faculty. We then graded the
      evidence using the EBM criteria as defined by the American Academy of Family
      Physicians. The same criteria were applied to extract evidence-based observations
      of problems in recruitment and retention for minority faculty. RESULTS: Of the
      548 studies identified and reviewed, 11 met inclusion criteria for this
      literature review. This article presents the data from the reviewed papers that
      described or evaluated minority faculty development programs. Faculty development
      programs in 15 different institutions showed mentoring and faculty development
      for minority faculty could increase retention, academic productivity, and
      promotion rates for this group. CONCLUSIONS: For medical schools to be successful
      in retention and recruitment of minority medical school faculty, specific
      programs need to be in place. Overall evidence is strong that faculty development
      programs and mentoring programs increase retention, productivity, and promotion
      for this group of medical faculty. This paper is a call to action for more
      faculty development and mentorship programs to reduce the disparities that exist
      between minority faculty and all other faculty members.

PMID- 24573518
TI  - Lebanese medical students' exposure to domestic violence: does it affect helping
      survivors?
AB  - BACKGROUND AND OBJECTIVES: Our purpose was to assess medical students'
      willingness to help women survivors of intimate partner violence (IPV) and its
      relation to past exposure to violence. METHODS: A cross-sectional study of
      medical students enrolled in three major universities in Beirut was carried out:
      545 students filled out a self-administered questionnaire. The Inventory of
      Beliefs About Wife Beating, the Attitudes Toward Women's scale, the Marriage Role
      Expectations Inventory, the Conflict Tactics scale, and the Trauma Symptoms scale
      were used. RESULTS: The majority (93.6%) of medical students believed that
      battered wives should be helped by either social or governmental agencies, but
      only 48% showed readiness to provide help themselves. Female medical students
      were significantly more likely to be willing to help survivors of violence,
      whereas students exposed to domestic violence in childhood were significantly
      less likely to do so. Female medical students previously exposed to violence had
      significantly higher scores on the Briere and Runtz's Trauma Symptom Checklist,
      indicating more negative trauma-related symptoms. Multivariate analysis revealed
      that the students' exposure to verbal aggression, their marital role
      expectations, attitudes toward women, and parents' marital status accounted for
      26% of the variability in the Helping Battered Wives score. CONCLUSIONS: The
      results of this study suggest that the medical students' past exposure to DV
      impacts their psychological well-being and their willingness to help abuse
      survivors. Given the multitude of stresses medical students are exposed to,
      careful attention and attendance to the effect of abuse on their well-being may
      be warranted.

PMID- 24573517
TI  - "Not a kidney or a lung:" research challenges in a network of safety net clinics.
AB  - BACKGROUND AND OBJECTIVES: To gain a better understanding of the facilitators and
      barriers to creating a practice-based research network (PBRN) of safety net
      clinics, we conducted a qualitative study within our network of safety net health
      centers. METHODS: Utilizing snowball sampling, we conducted interviews with 19 of
      our founding stakeholders and analyzed these interviews to draw out common
      themes. RESULTS: The results showed four barriers to research in our network:
      lack of research generated from clinician questions, lack of appropriate funding,
      lack of clinician time, and lack of infrastructure. We discuss these results and
      suggest that inadequate funding for practice-based research, particularly in the
      health care safety net, is a unifying theme of these four barriers. CONCLUSIONS:
      Our results suggest that the national funding strategy for research relevant to
      underserved populations and all of primary care must undergo a fundamental shift.
      We discuss the features of possible models to meet this need.

PMID- 24573520
TI  - Patient preferences in discussing sexual dysfunctions in primary care.
AB  - BACKGROUND AND OBJECTIVES: There are multiple barriers that limit patients and
      primary care physicians (PCPs) from discussing sexual dysfunctions (SDs) during
      medical appointments. Exploring patient preferences in discussing SDs with PCPs
      may help address some barriers, which can improve doctor-patient communication
      about SDs, delivery of health care, and patient quality of life. METHODS: A
      sample (n=108) of adult patients from an urban primary care clinic completed a 5-
      10 minute anonymous opinion questionnaire about their preferences in discussing
      SDs with PCPs. RESULTS: The majority of participants agreed that PCPs should give
      information to all patients (74%), ask all patients (69%), and have questions on
      medical history forms (55%) about SDs. Fifty-eight (58%) participants preferred
      to start the conversations about SDs with PCPs themselves, but all of these
      participants did not object to PCPs asking them about SDs. Participants who had
      ever experienced SD symptoms were more likely to want questions on medical
      history forms and for PCPs to ask about SDs. CONCLUSIONS: Participants preferred
      discussions about SDs with PCPs through various means (ie, medical history forms,
      medical appointments). Although participants were divided on who (patient versus
      PCP) should start conversations about SDs, the majority of participants did not
      object to PCPs inquiring about SDs during office visits or on medical history
      forms. Patients in poorer health and with self-reported SDs may need PCPs to
      inquire about SDs. Recommendations to improve health care delivery are suggested,
      including PCPs inquiring about SDs with all patients, especially with individuals
      in poorer health or with histories of SDs.

PMID- 24573519
TI  - Reinvigorating pediatric care in an academic family medicine practice.
AB  - BACKGROUND AND OBJECTIVES: Primary care access is critical for all populations,
      and family physicians remain a vital link to pediatric care, especially for
      rural/underserved areas and adolescents. Pediatric visits to family physicians
      have declined nationally, a trend also noted at the University of North Carolina
      (UNC) Family Medicine Center (FMC). Academic FMCs are challenged with maintaining
      their pediatric population in a competitive environment and providing excellent
      pediatric training to prepare residents to care for children. We investigated
      potential factors impacting pediatric visits with a goal of reversing this trend.
      We developed a 360-degree approach to examine and reinvigorate pediatric care and
      training in our practice. METHODS: To determine which aspects of our practice
      made pediatric care challenging, we conducted focus groups with parents of former
      and current FMC pediatric practices. We used billing data to assess pediatric
      patient volume and performed chart audits to examine preventive health visits,
      immunizations, and developmental screening. We anonymously contacted local family
      medicine and pediatric practices to compare services offered in their practice
      versus ours. Resident in-training exam scores and graduate surveys were reviewed
      to assess our pediatric training. RESULTS: Based on our evaluation, we identified
      and implemented improvements in the areas of clinical quality interventions,
      provider/education competency, and community marketing/relationships.
      CONCLUSIONS: A longitudinal evaluation and quality improvement initiative
      positively impacted our pediatric practice and training. The 360-degree approach
      of quality improvement may be useful for other academic family practices that are
      challenged with pediatric volume.

PMID- 24573521
TI  - Through the cracks.

PMID- 24573522
TI  - Treating the whole person: my journey to a career in family medicine.

PMID- 24573523
TI  - Finding forgiveness and purpose in family medicine.

PMID- 24573526
TI  - In celebration of Gene Farley: a founder of family medicine and champion of
      justice.

PMID- 24573527
TI  - Career success in academic family medicine.

PMID- 24573528
TI  - Never asking patients for money.

PMID- 24573529
TI  - Author's reply to never asking patients for money.

PMID- 24573530
TI  - The 20th scientific conference of the Society on NeuroImmune Pharmacology.
AB  - The 20th conference of the Society on NeuroImmune Pharmacology will be held March
      26-29, 2014. It features the latest in research examining the intersection of
      neuroscience, immunology and pharmacology, relevant for human health and disease.
      Particular emphases are placed on HIV and other infectious diseases, and abused
      substances, including illicit drugs and alcohol. 

PMID- 24573531
TI  - Observation on symmetry properties of sodium zinc(II)-2,9,16,23-phthalocyanine
      tetracarboxylate in water:NaOH solution.
AB  - The shift of the Q-band of sodium zinc(II)-2,9,16,23-phthalocyanine
      tetracarboxylate (ZnPc(COONa)4) to about 800 nm is attributed to the influence of
      the electron-donating property of the carboxylate groups substituted in the beta
      position. ZnPc(COONa)4 which was found to have a symmetry of D 2h characterized
      by a splitting of the Q transition. This splitting was interpreted by the
      formation of dianionic symmetric ZnPc(COONa)4 resulting from the dissociation of
      the pyrrole protons as well as the possibility of Na(+) dissolution of
      ZnPc(COONa)4 in the aqueous solution of NaOH. 

PMID- 24573532
TI  - Tangeretin, a citrus polymethoxyflavonoid, induces apoptosis of human gastric
      cancer AGS cells through extrinsic and intrinsic signaling pathways.
AB  - Tangeretin, a natural polymethoxyflavone present in citrus peel oil, is known to
      have anticancer activities in breast cancer, colorectal carcinoma and lung
      carcinoma, yet, the underlying mechanisms of tangeretin in human gastric cancer
      AGS cells have not been investigated to date. In the present study, the apoptotic
      mechanisms of tangeretin in AGS cells were explored. It was observed that
      tangeretin increased the apoptotic rates of AGS cells following treatment with
      tangeretin for 48 h in a dose-dependent manner by Annexin V-FITC and PI double
      staining. In addition, characteristic apoptotic morphology such as nuclear
      shrinkage and apoptotic bodies was observed after Hoechst 33258 staining. Flow
      cytometric assay showed that treatment of AGS cells with tangeretin decreased the
      mitochondrial membrane potential (MMP) in a dose-dependent manner, which
      indicated that mitochondrial dysfunction was involved in the tangeretin-induced
      apoptosis. Caspase-3, -8 and -9 activities were increased by tangeretin in a dose
      dependent manner. Western blotting showed that the protein levels of pro
      apoptotic proteins including cleaved caspase-3, cleaved caspase-8, cleaved
      caspase-9, Bax, Bid, tBid, p53, p21/cip1, Fas and FasL were significantly
      upregulated by tangeretin. In addition, PFT-alpha (a p53 inhibitor) reduced the
      apoptotic rates and the expression of p53, p21, caspase-3 and caspase-9 induced
      by tangeretin, indicating that tangeretin-induced apoptosis was p53-dependent. In
      conclusion, these results suggest that tangeretin induces the apoptosis of AGS
      cells mainly through p53-dependent mitochondrial dysfunction and the Fas/FasL
      mediated extrinsic pathway.

PMID- 24573534
TI  - The effective use of acai juice, blueberry juice and pineapple juice as negative
      contrast agents for magnetic resonance cholangiopancreatography in children.
AB  - Magnetic resonance cholangiopancreatography (MRCP) is commonly performed in the
      evaluation of known or suspected pancreaticobiliary disease in children. The
      administration of a negative oral contrast agent can improve the quality of the
      examination without significant additional cost. We describe our experience with
      certain brands of acai juice, blueberry juice and pineapple juice as negative
      oral contrast agents in children. We believe these fruit juices are safe,
      palatable and may improve MRCP image quality. 

PMID- 24573533
TI  - Mycetism: a review of the recent literature.
AB  - Approximately 100 of the known species of mushrooms are poisonous to humans. New
      toxic mushroom species continue to be identified. Some species initially
      classified as edible are later reclassified as toxic. This results in a
      continually expanding list of toxic mushrooms. As new toxic species are
      identified, some classic teachings about mycetism no longer hold true. As more
      toxic mushrooms are identified and more toxic syndromes are reported, older
      classification systems fail to effectively accommodate mycetism. This review
      provides an update of myscetism and classifies mushroom poisonings by the primary
      organ system affected, permitting expansion, as new, toxic mushroom species are
      discovered. 

PMID- 24573535
TI  - Gene profiling and bioinformatics analyses reveal time course differential gene
      expression in surgically resected colorectal tissues.
AB  - It has previously been reported that gene profiles in surgically-resected
      colorectal cancer tissues are altered over time possibly due to the different
      tissue-acquisition methods and sample extraction timing that were used. However,
      the changes that occur are still not clearly understood. In the present study,
      time-dependent changes in gene expression profiling in colorectal surgical
      specimens were analyzed. Normal and tumor tissues at several time-points (0, 30,
      60 and 120 min) were extracted, and RNA quality, microarray experiments,
      quantitative PCR and bioinformatics clustering were performed. Although RNA
      integrity was preserved 2 h after resection, inherent increased/decreased gene
      expression was observed from 30-120 min in approximately 10% of genes.
      Bioinformatics clustering could not distinguish case-by-case, probably due to
      gene profiling changes. Irregular changes in gene expression after surgical
      resection were found, which could be a crucial confounding factor for
      quantitative analyses.

PMID- 24573536
TI  - Comparison of sequential same-day middle ear surgeries: bilateral mastoidectomy,
      unilateral mastoidectomy with contralateral tympanoplasty, and bilateral
      tympanoplasty.
AB  - We evaluated the advantages and outcomes of performing bilateral simultaneous
      middle ear surgery for chronic otitis media. For comprehensive analysis, we
      compared three subgroups, bilateral mastoidectomy (MM), unilateral mastoidectomy
      with contralateral tympanoplasty (MT), and bilateral tympanoplasty (TT). A total
      of 176 ears of 85 patients with chronic otitis media or cholesteatoma underwent
      bilateral same-day surgery. The side with worse hearing was chosen for the first
      operation. In the absence of any intra-operative complications, the contralateral
      operation was then performed. Results of hearing tests did not differ
      significantly among the three groups except for gained decibels in the TT versus
      MT groups (P = 0.033). The correlation between pre-operative sound-field
      audiometry (SFA) and postoperative SFA was statistically significant. These
      results indicate that low frequency hearing was recovered immediately, but middle
      and high frequencies recovered later. Temporary taste change differed
      statistically among the three groups (P = 0.006). There were significantly more
      revision cases during the postoperative period in the groups that included
      mastoidectomy (MM group, MT group) (P = 0.035). Bilateral simultaneous middle ear
      surgery provides good hearing outcomes, reduces costs and operation times, and
      has a low incidence of complications. The results of our study may be helpful in
      guiding the otologist's decision when performing bilateral middle ear surgery.

PMID- 24573537
TI  - Differential regulation of B2-type CDK accumulation in Arabidopsis roots.
AB  - KEY MESSAGE: The accumulation of the mitotic B2-type CDK is tightly controlled by
      multiple pathways in Arabidopsis roots. Root growth depends on cell proliferation
      in the apices, which determines the root meristem size. The expression of B2-type
      cyclin-dependent kinase (CDKB2) is known to be restricted to dividing cells in
      the meristematic region, and therefore, the mechanisms controlling CDKB2
      accumulation may be associated with those determining the meristem size. We
      investigated how CDKB2 expression is controlled in distinct zones of Arabidopsis
      roots. We found that CDKB2;1 expression was induced by a member of the PLETHORA
      (PLT) family of transcription factors, which are known to mediate auxin signaling
      and maintain the undifferentiated state of meristematic cells. When the root
      meristem was treated with an auxin antagonist, the CDKB2;1 level was reduced not
      only by transcriptional suppression but also by proteasome-mediated protein
      degradation. This indicates that auxin promotes CDKB2 accumulation at both mRNA
      and protein levels in the meristem. In the elongation and differentiation zones,
      on the other hand, neither the ubiquitin-proteasome system nor the PLT-mediated
      transcriptional regulation is associated with CDKB2;1 accumulation. Both CDKB2;1
      and HIGH PLOIDY2 (HPY2), a SUMO E3 ligase, were ectopically accumulated in the
      stele when treated with exogenous auxin, suggesting the possibility that CDKB2;1
      accumulation is dependent on HPY2-mediated sumoylation, which is usually
      maintained by a higher auxin level in the meristem. Our results demonstrate that
      the CDKB2 level is tightly controlled by multiple pathways to maintain the
      mitotic activity in developing roots.

PMID- 24573539
TI  - The contributions of solar ultraviolet radiation exposure and other determinants
      to serum 25-hydroxyvitamin D concentrations in Australian adults: the AusD Study.
AB  - The Quantitative Assessment of Solar UV [ultraviolet] Exposure for Vitamin D
      Synthesis in Australian Adults (AusD) Study aimed to better define the
      relationship between sun exposure and serum 25-hydroxyvitamin D (25(OH)D)
      concentration. Cross-sectional data were collected between May 2009 and December
      2010 from 1,002 participants aged 18-75 years in 4 Australian sites spanning 24
      degrees  of latitude. Participants completed the following: 1) questionnaires on
      sun exposure, dietary vitamin D intake, and vitamin D supplementation; 2) 10 days
      of personal ultraviolet radiation dosimetry; 3) a sun exposure and physical
      activity diary; and 4) clinical measurements and blood collection for 25(OH)D
      determination. Our multiple regression model described 40% of the variance in
      25(OH)D concentration; modifiable behavioral factors contributed 52% of the
      explained variance, and environmental and demographic or constitutional variables
      contributed 38% and 10%, respectively. The amount of skin exposed was the single
      strongest contributor to the explained variance (27%), followed by location
      (20%), season (17%), personal ultraviolet radiation exposure (8%), vitamin D
      supplementation (7%), body mass index (weight (kg)/height (m)(2)) (4%), and
      physical activity (4%). Modifiable behavioral factors strongly influence serum
      25(OH)D concentrations in Australian adults. In addition, latitude was a strong
      determinant of the relative contribution of different behavioral factors. 

PMID- 24573540
TI  - Assessing mumps outbreak risk in highly vaccinated populations using spatial
      seroprevalence data.
AB  - Mumps is a potentially severe viral infection. The incidence of mumps has
      declined dramatically in high-income countries since the introduction of mumps
      antigen-containing vaccines. However, recent large outbreaks of mumps in highly
      vaccinated populations suggest waning of vaccine-induced immunity and primary
      vaccine failure. In this paper we present a simple method for identifying
      geographic regions with high outbreak potential, demonstrated using 2006 mumps
      seroprevalence data from Belgium and Belgian vaccination coverage data.
      Predictions of the outbreak potential in terms of the effective reproduction
      number in future years signal an increased risk of new mumps outbreaks.
      Literature reviews on serological information for both primary vaccine failure
      and waning immunity provide essential information for our predictions. Tailor
      made additional vaccination campaigns would be valuable for decreasing local
      pockets of susceptibility, thereby reducing the risk of future large-scale mumps
      outbreaks. 

PMID- 24573538
TI  - From exposures to population interventions: pregnancy and response to HIV
      therapy.
AB  - Many epidemiologic studies identify contrasts between an "always-exposed"
      population and a "never-exposed" population. Such "exposure effects" are perhaps
      most valuable in discussing individual lifestyle changes, or in clinical care;
      they may be less valuable in estimating the potential effects of realistic public
      health interventions. Various methods, among them population attributable
      fractions and generalized impact fractions, attempt to obtain more policy
      relevant estimates of "population intervention" effects, but such methods remain
      rare in the epidemiologic literature. Here, we describe the use of the parametric
      g-formula as a tool for the estimation of population intervention effects in
      longitudinal data. Our discussion is motivated by a previous study of the effect
      of incident pregnancy on time to virological failure among human immunodeficiency
      virus-positive women initiating antiretroviral therapy in South Africa between
      2004 and 2011. We show that 1) interventional estimates of effect can be
      estimated in longitudinal data using the parametric g-formula and 2) exposure
      effects and population interventional effects can have dramatically different
      interpretations and magnitudes in real-world data. Epidemiologists should
      consider estimating interventional effects in addition to exposure effects; doing
      so would allow the results of epidemiologic studies to be more immediately
      relevant to policy-makers and to implementation science efforts. 

PMID- 24573541
TI  - Only high levels of dabigatran attenuate catheter thrombosis in vitro and in
      rabbits.
AB  - In patients with mechanical heart valves, thromboembolic events were more
      frequent with dabigatran, an oral thrombin inhibitor, than with warfarin. This
      observation raises the possibility that dabigatran may be less effective than
      conventional anticoagulants in patients with other blood-contacting devices, such
      as catheters. To address this, we compared the capacity of dabigatran and/or
      heparin to inhibit catheter-induced thrombin generation in vitro and to attenuate
      catheter occlusion in rabbits. Using a catheter-induced thrombin generation
      assay, concentrations of dabigatran over 100 ng/ml prolonged the lag time and
      time to peak thrombin, and reduced the peak thrombin concentration and endogenous
      thrombin potential in a concentration-dependent fashion. Compared with saline in
      a rabbit model of catheter thrombosis, dabigatran prolonged the mean time to
      catheter occlusion by 2.9- and 1.9-fold when plasma levels were 173 and 140
      ng/ml, respectively; values comparable to median peak levels in humans given
      dabigatran 150 mg twice daily. In contrast, low-dose dabigatran, which produced a
      level of 60 ng/ml; a value comparable to the trough level of dabigatran in
      humans, did not prolong the time to occlusion. Whereas a 70 U/kg bolus of heparin
      prolonged the mean time to occlusion by 3.4-fold, a 15 U/kg bolus had no effect.
      When low-dose dabigatran was given in combination with 15 U/kg heparin, the mean
      time to occlusion was prolonged by 2.7-fold. These findings suggest that only
      peak levels of dabigatran are sufficient to prevent catheter-induced clotting
      unless supplemented heparin is given. 

PMID- 24573544
TI  - A highly permeable and selective amino-functionalized MOF CAU-1 membrane for CO2
      N2 separation.
AB  - A thin tubular CAU-1 membrane of 2-3 MUm exhibiting a high CO2 permeance of up to
      1.34 * 10(-6) mol m(-2) s(-1) Pa(-1) and a CO2-N2 selectivity of 17.4-22.8 for
      CO2-N2 mixtures was achieved, demonstrating for the first time that amino
      functionalized MOF membranes can provide high CO2-N2 selectivity and possess the
      potential for CO2 capture from flue gas. 

PMID- 24573542
TI  - Activated Wnt signaling induces myofibroblast differentiation of mesenchymal stem
      cells, contributing to pulmonary fibrosis.
AB  - Acute lung injury may lead to fibrogenesis. However, no treatment is currently
      available. This study was conducted to determine the effects of bone marrow
      derived mesenchymal stem cells (MSCs) in a model of HCl-induced acute lung injury
      in Sprague-Dawley (SD) rats. Stromal cell-derived factor (SDF)-1 and its receptor
      CXC chemokine receptor (CXCR)4 have been shown to participate in mobilizing MSCs.
      Adenovirus carrying the CXCR4 gene was used to transfect MSCs in order to
      increase the engraftment numbers of MSCs at injured sites. Histological
      examination data demonstrated that the engraftment of MSCs did not attenuate lung
      injury and pulmonary fibrosis. The results showed that engraftment of MSCs almost
      differentiated into myofibroblasts, but rarely differentiated into lung
      epithelial cells. Additionally, it was demonstrated that activated canonical
      Wnt/beta-catenin signaling in injured lung tissue regulated the myofibroblast
      differentiation of MSCs in vivo. The in vitro study results demonstrated that
      activation of the Wnt/beta-catenin signaling stimulated MSCs to express
      myofibroblast markers; however, this process was attenuated by Wnt antagonist
      DKK1. Therefore, the results demonstrated that the aberrant activation of Wnt
      signaling induces the myofibroblast differentiation of engrafted MSCs, thus
      contributing to pulmonary fibrosis following lung injury. 

PMID- 24573543
TI  - Digoxin use and risk of invasive breast cancer: evidence from the Nurses' Health
      Study and meta-analysis.
AB  - Despite preclinical evidence supporting anti-cancer effects of cardiac
      glycosides, epidemiologic studies consistently show elevated breast cancer risk
      in digoxin users. We studied this association in the Nurses' Health Study cohort
      to evaluate influences of screening mammography and lifestyle-related risk
      factors. We followed 90,202 postmenopausal women from 1994 to 2010. Self-reported
      breast cancers were confirmed by medical record review. We fit Cox regression
      models to estimate associations between time-varying digoxin use and breast
      cancer incidence, overall and by tumor ER status, accounting for mammography
      screening and established breast cancer risk factors. There were 5,004 digoxin
      users over 1.05 million person-years of observation, among whom 144 breast cancer
      cases occurred. Digoxin users were more likely to undergo mammographic screening,
      to be former users of postmenopausal hormones, and to take other medications than
      never-users; the groups were similar on reproductive history and alcohol
      consumption. Current digoxin use of >4-year duration was associated with a 45 %
      increased rate of breast cancer compared with never use (HRadj = 1.45, 95 % CI
      1.13-1.86). The association appeared stronger for ER-positive disease (HRadj =
      1.46, 95 % CI 1.10-1.95) than for ER-negative disease (HRadj = 1.12, 95 % CI 0.52
      2.37). Associations were robust to restriction on regular mammography use and to
      adjustment for established breast cancer risk factors, including lifestyle
      related exposures. The positive association between digoxin use and breast cancer
      occurrence was not attenuated when lifestyle-related breast cancer risk factors
      and screening practices were accounted for. Digoxin, a common cardiac drug
      worldwide, may promote breast carcinogenesis.

PMID- 24573547
TI  - Desmoid tumor mimicking GIST recurrence.

PMID- 24573548
TI  - Gynaecologists' awareness of bone healthcare in Switzerland.
AB  - PRINCIPLES: To assess gynaecologists' awareness of bone healthcare in women and
      the prevalence of application of national recommendations on bone healthcare in
      Switzerland. METHODS: During the annual meeting of the Swiss Society of
      Gynaecology and Obstetrics 2012, the Swiss Association against Osteoporosis
      (SVGO) performed standardised interviews with conference participants (n = 210).
      Questions addressed responsibility for bone healthcare, and whether diagnostic
      procedures, initiation of bone-specific treatment and follow-up were performed in
      accordance with SVGO recommendations. RESULTS: The majority of respondents were
      aged 30-50 years (60%), female (70%) and working as board-certified
      gynaecologists (69%). Ninety-three percent of respondents considered care for
      bone health as part of the gynaecologist's expertise. As diagnostic procedures,
      44% recommended performing bone densitometry (DXA) only, 34% ordered additional
      laboratory testing. Seventy-two percent of respondents initiated a bone-specific
      treatment. Predictors for not performing diagnostic procedures and not initiating
      a bone-specific treatment were physician's age below 30, being a trainee
      gynaecologist, and working at a university clinic. Particularly, young trainee
      gynaecologists working at a university clinic were especially unlikely to
      initiate a bone-specific treatment (regression coefficient = -2.68; odds ratio
      [OR] 0.069, 95% confidence interval [CI] 0.01-0.61; p = 0.16). Follow-ups were
      performed by 77% of respondents, but were less likely to be by female physicians
      (OR 0.27, 95% CI 0.09-0.84; p = 0.024). CONCLUSIONS: Although the majority of
      board-certified gynaecologists follow national recommendations on bone
      healthcare, current medical training in obstetrics and gynaecology does not
      sufficiently cover the subject of women's health. However, since this is a small
      study our findings may not reflect the findings in the total population.

PMID- 24573550
TI  - BRaf and MEK inhibitors differentially regulate cell fate and microenvironment in
      human hepatocellular carcinoma.
AB  - PURPOSE: Small molecule inhibitors of the mitogen-activated protein kinase (MAPK)
      pathway, such as sorafenib, represent novel treatment options for advanced
      hepatocellular carcinoma. The aim of our study was to identify downstream targets
      as biomarker candidates that are directly linked to the oncogenic MAPK pathway in
      hepatocellular carcinoma and correlate with inhibition of this pathway by
      multikinase inhibitors. EXPERIMENTAL DESIGN: Hepatocellular carcinoma cell lines
      and fresh tumor and tumor-free liver tissues from patients with hepatocellular
      carcinoma were incubated with different BRaf or MEK inhibitors and analyzed for
      kinase phosphorylation, proliferation, induction of apoptosis, and chemokine
      secretion. RESULTS: Hepatocellular carcinoma cell lines responded differentially
      to these inhibitors in a dose-dependent manner, even those targeting the same
      kinase. Sorafenib inhibited both MEK1 and ERK1/2 phosphorylation at high but
      increased signaling at low concentrations. Similarly, PLX4720 increased MEK/ERK
      signaling independently from mutations in BRaf or NRas. MEK inhibitors decreased
      ERK1/2 phosphorylation in a dose-dependent manner. These signaling
      characteristics correlated with inhibition of proliferation, induction of
      apoptosis, and chemokine secretion. Fresh tissues derived from patients diagnosed
      with primary hepatocellular carcinoma responded to these inhibitors with changes
      in their microenvironment following the patterns observed in hepatocellular
      carcinoma cells. CONCLUSIONS: Oncogenic signaling of the MAPK pathway influences
      hepatocellular carcinoma sensitivity to treatment with BRaf and MEK inhibitors
      about cell fate independently from mutations in BRaf and NRas. MAPK inhibitors
      have a strong impact on chemokine secretion as a consequence of interference with
      oncogenic signaling. Therefore, novel biomarker candidates associated with the
      hepatocellular carcinoma microenvironment may be developed for prediction and
      monitoring of treatment response to small molecule inhibitors.

PMID- 24573549
TI  - A peptide-based positron emission tomography probe for in vivo detection of
      caspase activity in apoptotic cells.
AB  - PURPOSE: Apoptosis, or programmed cell death, can be leveraged as a surrogate
      measure of response to therapeutic interventions in medicine. Cysteine aspartic
      acid-specific proteases, or caspases, are essential determinants of apoptosis
      signaling cascades and represent promising targets for molecular imaging. Here,
      we report development and in vivo validation of [(18)F]4-fluorobenzylcarbonyl-Val
      Ala-Asp(OMe)-fluoromethylketone ([(18)F]FB-VAD-FMK), a novel peptide-based
      molecular probe suitable for quantification of caspase activity in vivo using
      positron emission tomography (PET). EXPERIMENTAL DESIGN: Supported by molecular
      modeling studies and subsequent in vitro assays suggesting probe feasibility, the
      labeled pan-caspase inhibitory peptide, [(18)F]FB-VAD-FMK, was produced in high
      radiochemical yield and purity using a simple two-step, radiofluorination. The
      biodistribution of [(18)F]FB-VAD-FMK in normal tissue and its efficacy to predict
      response to molecularly targeted therapy in tumors was evaluated using microPET
      imaging of mouse models of human colorectal cancer. RESULTS: Accumulation of
      [(18)F]FB-VAD-FMK was found to agree with elevated caspase-3 activity in response
      to Aurora B kinase inhibition as well as a multidrug regimen that combined an
      inhibitor of mutant BRAF and a dual PI3K/mTOR inhibitor in (V600E)BRAF colon
      cancer. In the latter setting, [(18)F]FB-VAD-FMK PET was also elevated in the
      tumors of cohorts that exhibited reduction in size. CONCLUSIONS: These studies
      illuminate [(18)F]FB-VAD-FMK as a promising PET imaging probe to detect apoptosis
      in tumors and as a novel, potentially translatable biomarker for predicting
      response to personalized medicine.

PMID- 24573551
TI  - U.S. Food and Drug Administration approval: crizotinib for treatment of advanced
      or metastatic non-small cell lung cancer that is anaplastic lymphoma kinase
      positive.
AB  - On August 26, 2011, the U.S. Food and Drug Administration (FDA) approved
      crizotinib (XALKORI Capsules, Pfizer Inc.) for treatment of patients with locally
      advanced or metastatic non-small cell lung cancer (NSCLC) that is anaplastic
      lymphoma kinase (ALK) positive as detected by an FDA-approved test. The Vysis ALK
      Break-Apart FISH Probe Kit (Abbott Molecular, Inc.) was approved concurrently. In
      two multicenter, single-arm trials, patients with locally advanced or metastatic
      ALK-positive NSCLC previously treated with one or more systemic therapies
      received crizotinib orally at a dose of 250 mg twice daily. In 119 patients with
      ALK-positive NSCLC by local trial assay, the objective response rate (ORR) was
      61% [95% confidence intervals (CI), 52%-70%] with a median response duration of
      48 weeks. In 136 patients with ALK-positive NSCLC by the to-be-marketed test, the
      ORR was 50% (95% CI, 42%-59%) with a median response duration of 42 weeks. The
      most common adverse reactions (>=25%) were vision disorder, nausea, diarrhea,
      vomiting, edema, and constipation. Accelerated approval was granted on the basis
      of the high ORRs and durable responses. On November 20, 2013, crizotinib received
      full approval based on an improvement in progression-free survival in patients
      with metastatic ALK-positive NSCLC previously treated with one platinum-based
      chemotherapy regimen.

PMID- 24573552
TI  - Ultra low-dose IL-2 for GVHD prophylaxis after allogeneic hematopoietic stem cell
      transplantation mediates expansion of regulatory T cells without diminishing
      antiviral and antileukemic activity.
AB  - PURPOSE: GVHD after allogeneic hematopoietic stem cell transplantation (alloSCT)
      has been associated with low numbers of circulating CD4(+)CD25(+)FoxP3(+)
      regulatory T cells (Tregs). Because Tregs express high levels of the interleukin
      (IL)-2 receptor, they may selectively expand in vivo in response to doses of IL-2
      insufficient to stimulate T effector T-cell populations, thereby preventing GVHD.
      EXPERIMENTAL DESIGN: We prospectively evaluated the effects of ultra low-dose
      (ULD) IL-2 injections on Treg recovery in pediatric patients after alloSCT and
      compared this recovery with Treg reconstitution post alloSCT in patients without
      IL-2. Sixteen recipients of related (n = 12) or unrelated (n = 4) donor grafts
      received ULD IL-2 post hematopoietic stem cell transplantation (HSCT; 100,000
      200,000 IU/m(2) *3 per week), starting <day 30 and continuing for 6 to 12 weeks.
      RESULTS: No grade 3/4 toxicities were associated with ULD IL-2.
      CD4(+)CD25(+)FoxP3(+) Tregs increased from a mean of 4.8% (range, 0%-11.0%) pre
      IL-2 to 11.1% (range, 1.2%-31.1%) following therapy, with the greatest change
      occurring in the recipients of matched related donor (MRD) transplants. No IL-2
      patients developed grade 2-4 acute GVHD (aGVHD), compared with 4 of 33 (12%) of
      the comparator group who did not receive IL-2. IL-2 recipients retained T cells
      reactive to viral and leukemia antigens, and in the MRD recipients, only 2 of 13
      (15%) of the IL-2 patients developed viral infections versus 63% of the
      comparator group (P = 0.022). CONCLUSIONS: Hence, ULD IL-2 is well tolerated,
      expands a Treg population in vivo, and may be associated with a lower incidence
      of viral infections and GVHD.

PMID- 24573553
TI  - Imaging the norepinephrine transporter in neuroblastoma: a comparison of [18F]
      MFBG and 123I-MIBG.
AB  - PURPOSE: The norepinephrine transporter (NET) is a critical regulator of
      catecholamine uptake in normal physiology and is expressed in neuroendocrine
      tumors like neuroblastoma. Although the norepinephrine analog, meta
      iodobenzylguanidine (MIBG), is an established substrate for NET, (123)I/(131)I
      MIBG has several clinical limitations for diagnostic imaging. In the current
      studies, we evaluated meta-[(18)F]-fluorobenzylguanidine ([(18)F]-MFBG) and
      compared it with (123)I-MIBG for imaging NET-expressing neuroblastomas.
      EXPERIMENTAL DESIGN: NET expression levels in neuroblastoma cell lines were
      determined by Western blot and (123)I-MIBG uptake assays. Five neuroblastoma cell
      lines and two xenografts (SK-N-BE(2)C and LAN1) expressing different levels of
      NET were used for comparative in vitro and in vivo uptake studies. RESULTS: The
      uptake of [(18)F]-MFBG in cells was specific and proportional to the expression
      level of NET. Although [(18)F]-MFBG had a 3-fold lower affinity for NET and an
      approximately 2-fold lower cell uptake in vitro compared with that of (123)I
      MIBG, the in vivo imaging and tissue radioactivity concentration measurements
      demonstrated higher [(18)F]-MFBG xenograft uptake and tumor-to-normal organ
      ratios at 1 and 4 hours after injection. A comparison of 4 hours [(18)F]-MFBG PET
      (positron emission tomography) imaging with 24 hours (123)I-MIBG SPECT (single
      photon emission computed tomography) imaging showed an approximately 3-fold
      higher tumor uptake of [(18)F]-MFBG, but slightly lower tumor-to-background
      ratios in mice. CONCLUSIONS: [(18)F]-MFBG is a promising radiopharmaceutical for
      specifically imaging NET-expressing neuroblastomas, with fast pharmacokinetics
      and whole-body clearance. [(18)F]-MFBG PET imaging shows higher sensitivity,
      better detection of small lesions with low NET expression, allows same day
      scintigraphy with a shorter image acquisition time, and has the potential for
      lower patient radiation exposure compared with (131)I/(123)I-MIBG.

PMID- 24573554
TI  - High-throughput detection of clinically relevant mutations in archived tumor
      samples by multiplexed PCR and next-generation sequencing.
AB  - PURPOSE: Tailoring cancer treatment to tumor molecular characteristics promises
      to make personalized medicine a reality. However, reliable genetic profiling of
      archived clinical specimens has been hindered by limited sensitivity and high
      false-positive rates. Here, we describe a novel methodology, MMP-seq, which
      enables sensitive and specific high-throughput, high-content genetic profiling in
      archived clinical samples. EXPERIMENTAL DESIGN: We first validated the technical
      performance of MMP-seq in 66 cancer cell lines and a Latin square cross-dilution
      of known somatic mutations. We next characterized the performance of MMP-seq in
      17 formalin-fixed paraffin-embedded (FFPE) clinical samples using matched fresh
      frozen tissue from the same tumors as benchmarks. To demonstrate the potential
      clinical utility of our methodology, we profiled FFPE tumor samples from 73
      patients with endometrial cancer. RESULTS: We demonstrated that MMP-seq enabled
      rapid and simultaneous profiling of a panel of 88 cancer genes in 48 samples, and
      detected variants at frequencies as low as 0.4%. We identified DNA degradation
      and deamination as the main error sources and developed practical and robust
      strategies for mitigating these issues, and dramatically reduced the false
      positive rate. Applying MMP-seq to a cohort of endometrial tumor samples
      identified extensive, potentially actionable alterations in the PI3K
      (phosphoinositide 3-kinase) and RAS pathways, including novel PIK3R1 hotspot
      mutations that may disrupt negative regulation of PIK3CA. CONCLUSIONS: MMP-seq
      provides a robust solution for comprehensive, reliable, and high-throughput
      genetic profiling of clinical tumor samples, paving the way for the incorporation
      of genomic-based testing into clinical investigation and practice.

PMID- 24573555
TI  - Repeatability of quantitative FDG-PET/CT and contrast-enhanced CT in recurrent
      ovarian carcinoma: test-retest measurements for tumor FDG uptake, diameter, and
      volume.
AB  - PURPOSE: Repeatability of baseline FDG-PET/CT measurements has not been tested in
      ovarian cancer. This dual-center, prospective study assessed variation in tumor
      2[18F]fluoro-2-deoxy-D-glucose (FDG) uptake, tumor diameter, and tumor volume
      from sequential FDG-PET/CT and contrast-enhanced computed tomography (CECT) in
      patients with recurrent platinum-sensitive ovarian cancer. EXPERIMENTAL DESIGN:
      Patients underwent two pretreatment baseline FDG-PET/CT (n = 21) and CECT (n =
      20) at two clinical sites with different PET/CT instruments. Patients were
      included if they had at least one target lesion in the abdomen with a
      standardized uptake value (SUV) maximum (SUVmax) of >= 2.5 and a long axis
      diameter of >= 15 mm. Two independent reading methods were used to evaluate
      repeatability of tumor diameter and SUV uptake: on site and at an imaging
      clinical research organization (CRO). Tumor volume reads were only performed by
      CRO. In each reading set, target lesions were independently measured on
      sequential imaging. RESULTS: Median time between FDG-PET/CT was two days (range 1
      7). For site reads, concordance correlation coefficients (CCC) for SUVmean,
      SUVmax, and tumor diameter were 0.95, 0.94, and 0.99, respectively. Repeatability
      coefficients were 16.3%, 17.3%, and 8.8% for SUVmean, SUVmax, and tumor diameter,
      respectively. Similar results were observed for CRO reads. Tumor volume CCC was
      0.99 with a repeatability coefficient of 28.1%. CONCLUSIONS: There was excellent
      test-retest repeatability for FDG-PET/CT quantitative measurements across two
      sites and two independent reading methods. Cutoff values for determining change
      in SUVmean, SUVmax, and tumor volume establish limits to determine metabolic
      and/or volumetric response to treatment in platinum-sensitive relapsed ovarian
      cancer.

PMID- 24573558
TI  - ECR 2014, Part A.

PMID- 24573559
TI  - ECR 2014, Part B.

PMID- 24573557
TI  - An assessment of time involved in pre-test case review and counseling for a whole
      genome sequencing clinical research program.
AB  - Whole genome sequencing (WGS) is being used for evaluation of individuals with
      undiagnosed disease of suspected genetic origin. Implementing WGS into clinical
      practice will place an increased burden upon care teams with regard to pre-test
      patient education and counseling about results. To quantitate the time needed for
      appropriate pre-test evaluation of participants in WGS testing, we documented the
      time spent by our clinical research group on various activities related to
      program preparation, participant screening, and consent prior to WGS.
      Participants were children or young adults with autism, intellectual or
      developmental disability, and/or congenital anomalies, who have remained
      undiagnosed despite previous evaluation, and their biologic parents. Results
      showed that significant time was spent in securing allocation of clinical
      research space to counsel participants and families, and in acquisition and
      review of participant's medical records. Pre-enrollment chart review identified
      two individuals with existing diagnoses resulting in savings of $30,000 for the
      genome sequencing alone, as well as saving hours of personnel time for genome
      interpretation and communication of WGS results. New WGS programs should plan for
      costs associated with additional pre-test administrative planning and patient
      evaluation time that will be required to provide high quality care. 

PMID- 24573560
TI  - ECR 2014, Part C.

PMID- 24573556
TI  - Ubiquitin-like with PHD and ring finger domains 2 is a predictor of survival and
      a potential therapeutic target in colon cancer.
AB  - In the present study, we investigated the expression of ubiquitin-like with PHD
      and ring finger domains 2 (UHRF2) in colon cancer and adjacent normal tissues and
      estimated the clinicopathological significance and predictive value of UHRF2
      expression in colon cancer. Using quantitative real-time PCR, tissue microarray
      (TMA), western blot analysis and immunohistochemical staining, we evaluated UHRF2
      mRNA and protein levels in tumor tissues and paired adjacent normal epithelium.
      We found that UHRF2 was upregulated at both the transcriptional and translational
      levels in tumor tissues. Immunohistochemical detection of UHRF2 on a TMA
      containing 203 paired specimens showed that increased cytoplasmic UHRF2 was
      significantly associated with clinical stage, depth of invasion, nodal
      involvement, tumor histologic grade and the presence of metastasis. Patients with
      UHRF2-positive tumors had a much lower disease-free survival [hazard ratio (HR)
      9.511, P<0.001] and overall survival (HR 9.820, P<0.001). Univariate and
      multivariate analyses were performed to determine the correlation between these
      parameters and the clinical and pathological variables of the study population
      verifying that UHRF2 immunoreactivity emerged as an independent prognostic factor
      in the multivariate analysis. UHRF2 may contribute to the progression of colon
      carcinogenesis and function as a novel prognostic indicator after curative
      operation.

PMID- 24573561
TI  - ECR 2014, Part D.

PMID- 24573562
TI  - ECR 2014, Part E.

PMID- 24573563
TI  - ECR 2014, Part G.

PMID- 24573564
TI  - ECR 2014, Part F.

PMID- 24573565
TI  - An enhanced model of cross-bridge operation with internal elasticity.
AB  - A recent study has shown (as reported by Rosenfeld, Eur Biophys J 41:733-753,
      2012) that an apparatus consisting of a cycling pump, a lever, and charged beads
      is able to generate force in accordance with Hill's force-velocity relation.
      Here, we show that a spring integrated into this microscopic model of a myosin
      motor allows reproducing, in general terms, the muscle fiber responses to sudden
      changes in fiber length. The time course of relaxation is governed by the same
      hindering force that determines the maximal value of muscle contraction velocity.
      Any single one of the exceptionally simple parts of the proposed model device
      corresponds to some element of the real myosin head and interacts with any other
      part in accordance with the laws of Newton, Coulomb, and Hooke. In essence, the
      model demonstrates that Coulomb repulsion should be understood as the physical
      source of muscle force. Accordingly, some fictitious master equation with ad hoc
      postulated rate constants is not needed to explain the essential mechanical
      characteristics of a muscle. The current model still contains no mechanism that
      could account for superfast relaxations within periods of about 0.1 ms.

PMID- 24573566
TI  - Determination of common urine substances as an assay for improving prostate
      carcinoma diagnostics.
AB  - Recently, interest in the identification of non-invasive markers for prostate
      carcinoma detectable in the urine of patients has increased. In this study, we
      monitored the abundance of potential non-invasive markers of prostate carcinoma
      such as amino acid sarcosine, involved in the metabolism of amino acids and
      methylation processes, ongoing during the progression of prostate carcinoma. in
      addition, other potential prostate tumor markers were studied. The most
      significant markers, prostate-specific antigen (PSA) and free PSA (fPSA), already
      used in clinical diagnosis, were analyzed using an immunoenzymometric assay.
      Whole amino acid profiles were also determined to evaluate the status of amino
      acids in patient urine samples and to elucidate the possibility of their
      utilization for prostate carcinoma diagnosis. To obtain the maximum amount of
      information, the biochemical parameters were determined using various
      spectrophotometric methods. All results were subjected to statistical processing
      for revealing different correlations between the studied parameters. We observed
      alterations in most of the analyzed substances. Based on the results obtained, we
      concluded that the specificity of prostate carcinoma diagnosis could be improved
      by determination of common urine metabolites, since we compiled a set of tests,
      including the analysis of sarcosine, proline, PSA and uric acid in the urine.
      These metabolites were not observed in the urine obtained from healthy subjects,
      while their levels were elevated in all patients suffering from prostate
      carcinoma. 

PMID- 24573567
TI  - Assessment of vascular contrast and wall motion of the aortic root and ascending
      aorta on MDCT angiography: dual-source high-pitch vs non-gated single-source
      acquisition schemes.
AB  - OBJECTIVES: This retrospective study assessed whether dual-source high-pitch
      computed tomographic angiography (CTA) offered advantages over single-source
      standard-pitch techniques in the evaluation of the ascending aorta. METHODS:
      Twenty patients who received both thoracic dual-source high-pitch and single
      source standard-pitch CTAs within 1 year were assessed. Dual-source CTAs were
      performed; standard-pitch imaging used dose-modulated 120 kVp/150 mAs and 0.8
      pitch compared with high-pitch protocols employing dose-modulated 120 kVp/250 mAs
      and 2.4 target pitch. Radiation dose was documented. Contrast-to-noise ratios
      (CNRs) at sinuses of the Valsalva (CNRValsalva) and ascending aorta (CNRAorta)
      were calculated. Dose/CNR for each technique was compared with paired t-tests.
      Motion at aortic valve, aortic root and ascending aorta were assessed with four
      point scales and Mann-Whitney U tests; longitudinal extension of motion was
      compared with paired t-tests. RESULTS: Significantly lower motion scores for high
      pitch, compared with standard-pitch acquisitions for aortic annulus, 0 vs. 2,
      aortic root, 0 vs. 3, and ascending aorta, 0 vs. 2, were achieved. Significantly
      reduced longitudinal extension of motion at aortic root, 4.9 mm vs 15.7 mm, and
      ascending aorta, 4.9 mm vs 21.6 mm, was observed. Contrast was not impacted:
      CNRValsalva, 45.6 vs 46.3, and CNRAorta, 45.3 vs 47.1. CTDIvol was significantly
      decreased for high-pitch acquisitions, 13.9 mGy vs 15.8 mGy. CONCLUSIONS: Dual
      source high-pitch CTAs significantly decreased motion artefact without negatively
      impacting vascular contrast and radiation dose. KEY POINTS: * Dual-source high
      pitch CTA significantly decreased motion artefact of the ascending aorta. * Dual
      source high-pitch CTA did not negatively impact on vascular contrast. * Dual
      source high-pitch CTA significantly decreased radiation dose compared with single
      source standard-pitch acquisitions.

PMID- 24573568
TI  - Relapse of IgG4-related sclerosing cholangitis after steroid therapy: image
      findings and risk factors.
AB  - OBJECTIVES: To compare imaging data from IgG4-related sclerosing cholangitis
      (IgG4-SC) obtained at initial attack and at relapse, and to determine risk
      factors predicting relapse of IgG4-SC after steroid therapy. METHODS: Twenty
      three patients with relapsed IgG4-SC and 36 non-relapsed patients were included.
      Computed tomography, magnetic resonance cholangiography, and endoscopic
      retrograde cholangiography were used to determine biliary and extrabiliary
      involvement. Images taken at the time of the initial attack were compared with
      those taken at relapse. Risk factors were determined by comparing clinical and
      imaging factors in the relapse and non-relapse groups. RESULTS: In comparison to
      the initial attack, relapsed IgG4-SC was characterised by more frequent
      extrapancreatic and multiple bile duct strictures, increased bile duct segment
      involvement, thicker bile duct walls, and a less frequent association with
      autoimmune pancreatitis (AIP) (P <= 0.016). Compared with non-relapse, relapse
      was significantly associated with less frequent use of maintenance steroid
      therapy, more frequent extrapancreatic and multiple bile duct strictures,
      increased bile duct segment involvement, and thicker bile duct walls during the
      initial attack (P <= 0.021). CONCLUSIONS: Relapsed IgG4-SC presented with a more
      aggressive appearance on imaging than the initial attack. The degree of bile duct
      involvement and use of maintenance steroid therapy were associated with relapse
      of IgG4-SC.

PMID- 24573569
TI  - MR imaging and T2 measurements in peripheral nerve repair with activation of Toll
      like receptor 4 of neurotmesis.
AB  - OBJECTIVE: To investigate the role of MR imaging in neurotmesis combined with
      surgical repair and Toll-like receptor 4 (TLR4) activation. METHODS: Forty-eight
      rats received subepineurial microinjection of the TLR4 agonist lipopolysaccharide
      (LPS, n = 24) or phosphate buffered saline (PBS, n = 24) immediately after
      surgical repair of the transected sciatic nerve. Sequential fat-suppressed T2
      weighted imaging and quantitative T2 measurements were obtained at 3, 7, 14 and
      21 days after surgery, with histologic assessments performed at regular
      intervals. T2 relaxation times and histological quantification of the distal
      stumps were measured and compared. RESULTS: The distal stumps of transected
      nerves treated with LPS or PBS both showed persistent enlargement and
      hyperintense signal. T2 values of the distal stumps showed a rapid rise to peak
      level followed by a rapid decline pattern in nerves treated with LPS, while
      exhibiting a slow rise to peak value followed by a slow decline in nerves treated
      with PBS. Nerves treated with LPS exhibited more prominent macrophage
      recruitment, faster myelin debris clearance and more pronounced nerve
      regeneration. CONCLUSION: Nerves treated with TLR4 activation had a
      characteristic pattern of T2 value change over time. Longitudinal T2 measurements
      can be used to detect the enhanced repair effect associated with TLR4 activation
      in the surgical repair of neurotmesis. KEY POINTS: * TLR4 activation had
      additional beneficial effects on neurotmesis beyond surgical repair. * TLR4
      activation had a characteristic time course of T2 values. * T2 measurements can
      help detect beneficial effects with TLR4 activation.

PMID- 24573570
TI  - [Prostate cancer].
AB  - For many clinical issues regarding prostate cancer magnetic resonance imaging
      (MRI) is gaining increasing importance for prostate diagnostics. The high
      morphological resolution of T2-weighted sequences is unsurpassed compared to
      other imaging modalities. It enables not only the detection and localization of
      prostate cancer but also allows the evaluation of extracapsular extensions.
      Functional MRI methods, such as diffusion-weighted imaging (DWI), dynamic
      contrast-enhanced (DCE) MRI and proton magnetic resonance spectroscopy ((1)H-MRS)
      increase the specificity and to a lesser extent, the sensitivity of diagnostics.
      In accordance with the interdisciplinary S3 guidelines, prostate MRI is
      recommended for patients with at least one negative biopsy for cancer detection.
      According to the guidelines areas suspected of being cancerous should be
      selectively biopsied in addition to the systematic biopsy. The transmission of
      findings about the suspected tumor areas according to the structured PI-RADS
      classification system has proven its worth. The localization and staging of
      prostate carcinoma is best achieved with the help of MRI and is recommended in
      the S3 guidelines especially for tumors with a clinical stage cT3/4 or with a
      Gleason grading system score >=8. In addition to these applications MRI is mainly
      used under study conditions for local recurrence or active surveillance. 

PMID- 24573571
TI  - Intraobserver and interobserver agreement in the classification and treatment of
      midshaft clavicle fractures.
AB  - BACKGROUND: With the recent emphasis on performing open reduction and internal
      fixation on midshaft clavicle fractures with complete displacement, comminution,
      and >2 cm of shortening, it is important to determine the reliability of
      orthopaedic surgeons to assess these variables on standard plain radiographs and
      to determine the agreement among orthopaedic surgeons in choosing the treatment.
      PURPOSE: To determine the intra- and interobserver reliability in the
      classification of midshaft clavicle fractures via standard plain radiographs and
      to determine the intra- and interobserver agreement in the treatment of these
      fractures. STUDY DESIGN: Cohort study (diagnosis); Level of evidence, 3. METHODS:
      Charts of patients seen by the 2 senior authors from 2006 to 2011 were reviewed
      to identify patients treated for clavicle fractures (CPT codes 23500 and 23515).
      Anteroposterior and 30 degrees  cephalad radiographs were selected, representing
      midshaft clavicle fractures treated both operatively and nonoperatively. Thirty
      pairs of radiographs were included in the investigation. The radiographs were
      standardized for size to allow accurate measurements within a non-PACS (picture
      archiving and communications system) program, and a PDF document was created with
      all representative radiographs. Clinical scenarios were created for each set of
      radiographs, and the evaluators were asked to (1) measure the degree of
      shortening in millimeters, (2) determine the percentage displacement, (3)
      determine whether the fracture was comminuted, and (4) state whether they would
      treat the fracture operatively or nonoperatively. The radiographs, along with
      instructions on how to use the measuring tool with Adobe Reader, were distributed
      to 22 shoulder/sports medicine fellowship-trained orthopaedic surgeons, then
      reordered and redistributed approximately 3 months later. Sixteen surgeons
      completed 1 round of surveys, and 13 surgeons completed both rounds. RESULTS:
      Interrater agreement was moderate for displacement of 0%-49% (kappa = 0.71, P <
      .001) and >100% (kappa = 0.73, P < .001), with minimal agreement for displacement
      of 50%-100% (kappa = 0.39, P < .001). There was moderate interrater agreement for
      the presence/absence of comminution (kappa = 0.75, P < .001). Interrater
      agreement was weak for shortening of 0-5.0 mm (kappa = 0.58, P < .001) and >30.0
      mm (kappa = 0.51, P < .001), with minimal agreement for shortening of 5.1-10.0 mm
      (kappa = 0.22, P < .001) and no agreement for the other 4 categories. Interrater
      analysis showed weak agreement on whether surgical treatment was recommended
      (kappa = 0.40, P < .001). Intrarater agreement was strong for comminution (kappa
      = 0.80, P < .0001), moderate for both displacement (kappa = 0.76, P < .001) and
      operative treatment (kappa = 0.64, P < .001), and minimal for shortening (kappa =
      0.38, P < .001). The following variables statistically predicted whether surgery
      was recommended (P < .001): (1) the odds of surgery were 2.26 if comminution was
      noted, holding displacement and the interaction between displacement and
      shortening constant, and (2) the odds of surgery were 3.37 if there is
      displacement of >100% compared with displacement of 0%-49%, holding comminution
      and shortening constant. CONCLUSION: Standard plain unilateral radiographs of the
      clavicle are insufficient to reliably determine the degree of shortening of
      clavicle fractures and the need for surgery among shoulder/sports medicine
      fellowship-trained orthopaedic surgeons. Consideration should be made to not use
      shortening as the sole determinant for whether to proceed with surgical
      intervention or to use other radiographic modalities to determine the amount of
      shortening.

PMID- 24573572
TI  - Chemical pleurodesis using a Viscum album extract in infants with congenital
      chylothorax.
AB  - Congenital chylothorax is a rare condition, but it is the most common cause of
      pleural effusion in neonates and infants. Here, we report on the first trials of
      the intrapleural instillation of an extract of Viscum album (European mistletoe)
      (Abnobaviscum Q(r)) in two infants with congenital chylothorax that was
      refractory to standard conservative management and thoracic duct ligation.
      CONCLUSION: The clinical course of both children improved with no side effects
      related to the extract after following up the children for 2 years and 9 months,
      respectively. Randomized multicenter prospective studies will help determine the
      effectiveness of pleurodesis with a V. album extract and the occurrence of long
      term side effects with this agent.

PMID- 24573573
TI  - Neurodevelopmental impairment in preterm infants with late-onset infection: not
      only in extremely preterm infants.
AB  - Late-onset infection is known to increase the risk of neurodevelopmental
      impairment in infants born extremely preterm. However, little data is available
      regarding infants born moderately preterm. The aim of this study was to determine
      whether late-onset infection in moderately preterm infants (<35 weeks of
      gestation) was associated with a non-optimal neurodevelopmental outcome at 2
      years of age. We analyzed a regional, population-based cohort of infants (LIFT
      cohort) between January 2003 and December 2009, and we used a propensity score
      method to reduce bias. Among the 4,618 preterm infants assessed at 2 years, 618
      had acquired late-onset infection (13.4 %), and 764 had a non-optimal outcome
      (16.5 %). The rate of non-optimal outcomes was significantly higher in preterm
      infants with late-onset infection, irrespective of subgroups of gestational age
      and birth weight Z-score. After adjusting for the propensity score, the
      relationship between late-onset infection and non-optimal neurodevelopmental
      outcome at 2 years among infants born before 35 weeks of gestation remained
      significant (aOR = 1.3; 95 % CI 1.01-1.7; p = .04). CONCLUSION: Late-onset
      infection is associated with poor neurological outcome at 2 years of age among
      infants born moderately preterm before and after adjustment for the propensity
      score.

PMID- 24573574
TI  - High expression of the secreted protein dickkopf homolog 4: roles in invasion and
      metastasis of renal cell carcinoma and its association with Von Hippel-Lindau
      gene.
AB  - The aim of this study was to investigate the effects of the dickkopf homolog 4
      (DKK4)/Wnt/beta-catenin signaling pathway on tumorigenesis and metastasis in
      clear cell renal cell carcinoma (ccRCC), as well as to elucidate the underlying
      mechanisms. We examined the expression of DKK4 in 30 cases of ccRCC and matched
      adjacent normal tissues, and investigated its correlation with
      clinicopathological characteristics. Stable DKK4-transfected cells were
      established, and DKK4 functional analyses were performed, including a T-cell
      factor/lymphoid enhancer factor (TCF/LEF) reporter assay, and experiments on cell
      viability, apoptosis, invasive capability and tumor growth in vivo. Finally,
      western blot analysis was performed to detect Von Hippel-Lindau (VHL) expression
      in 50 clinical specimens. The expression levels of the DKK4, beta-catenin and
      beta-catenin downstream target genes, cyclin D1 and c-myc, were determined in the
      these specimens, as well as in RCC4(-), T3-14(+) cell lines by qRT-PCR and
      western blot analysis. The same tests were also performed in human embryonic
      kidney (HEK)293 cells which were transfected with the pCDH-DKK4 plasmid. After 6
      weeks the tumor weight significantly increased in the mice transfected with the
      tumor cells. DKK4 mRNA and protein expression levels were significantly
      upregulated (p<0.001). DKK4 was distinctly overexpressed (68.0%) in all patient
      tissues. VHL(-) samples accounted for 60.0% of all samples, while DKK4 expression
      was significantly upregulated in 50% of these samples, indicating a correlation
      with VHL(-) expression (r=0.403, p<0.05). We also observed reduced expression
      levels of cyclin D1, c-myc and beta-catenin (to a greater extent) in the VHL(-),
      RCC4(-) and T3-14(+) cells, as well as in the stably transfected HEK293 cells.
      DKK4 may be an oncogene, and its upregulated expression may be involved in the
      pathogenesis of ccRCC as a downstream gene of VHL. By activating other pathways
      apart from the Wnt/beta-catenin pathway, DKK4 may play an important role in ccRCC
      tumorigenesis and metastasis.

PMID- 24573575
TI  - Synthesis of benzo-gamma-sultams via the Rh-catalyzed aromatic C-H
      functionalization of diazosulfonamides.
AB  - An efficient synthesis of 1-aryl-benzo-gamma-sultams, 1-aryl-1,3
      dihydrobenzo[c]isothiazole-2,2-dioxides, was achieved in 65-99% yields via the Rh
      catalyzed intramolecular aromatic C-H functionalization of N,N-diaryl
      diazosulfonamides with 0.5 mol% Rh2(oct)4 as the catalyst. 

PMID- 24573576
TI  - Monitoring subcellular biotransformation of N-L-leucyldoxorubicin by micellar
      electrokinetic capillary chromatography coupled to laser-induced fluorescence
      detection.
AB  - Development of prodrugs is a promising alternative to address cytotoxicity and
      nonspecificity of common anticancer agents. N-L-leucyldoxorubicin (LeuDox) is a
      prodrug that is biotransformed to the anticancer drug doxorubicin (Dox) in the
      extracellular space; however, its biotransformation may also occur
      intracellularly in endocytic organelles. Such organelle-specific
      biotransformation is yet to be determined. In this study, magnetically enriched
      endocytic organelle fractions from human uterine sarcoma cells were treated with
      LeuDox. Micellar electrokinetic chromatography with laser-induced fluorescence
      detection (MEKC-LIF) was used to determine that 10% of LeuDox was biotransformed
      to Dox, accounting for ~43% of the biotransformation occurring in the post
      nuclear fraction. This finding suggests that endocytic organelles also
      participate in the intracellular biotransformation of LeuDox to Dox.

PMID- 24573577
TI  - Development of a haemolytic-enzymatic assay with mediated amperometric detection
      for palytoxin analysis: application to mussels.
AB  - An electrochemical sensor for palytoxin (PlTX) detection, based on a strip of
      eight screen-printed electrodes connected to a cost-effective and portable
      apparatus, is reported. Sheep erythrocytes were used to test the palytoxin
      detector and degree of haemolysis was evaluated by measuring release of the
      cytosolic lactate dehydrogenase (LDH). Percentage haemolysis and, therefore, the
      amount of LDH measured, by use of NADH/pyruvate and appropriate electrochemical
      mediators, was correlated with the concentration of the toxin. Two different
      electrochemical approaches were investigated for evaluation of LDH release, but
      only one based on the use of a binary redox mediator sequence (phenazine
      methosulfate in conjugation with hexacyanoferrate(III)) proved useful for our
      purpose. After analytical and biochemical characterization, the sensor strip was
      used to measure palytoxin. Sheep blood and standard solutions of PlTX were left
      to react for two different incubation times (24 h or 4 h), resulting in working
      ranges of 7 * 10(-3)-0.02 ng mL(-1) and 0.16-1.3 ng mL(-1), respectively. The
      specificity of the test for palytoxin was evaluated by use of ouabain, which acts
      in the same way as PlTX on the Na(+)/K(+)-ATPase pump. A cross-reactivity study,
      using high concentrations of other marine biotoxins was also conducted.
      Experiments to evaluate the matrix effect and recovery from mussels are
      discussed.

PMID- 24573579
TI  - Ionic liquid-modified magnetic polymeric microspheres as dispersive solid phase
      extraction adsorbent: a separation strategy applied to the screening of
      sulfamonomethoxine and sulfachloropyrazine from urine.
AB  - Ionic liquid-modified magnetic polymeric microspheres (ILMPM) were prepared based
      on Fe3O4 magnetic nanoparticles (MNPs) and ionic liquids (ILs) incorporated into
      a polymer. The composites were characterized using scanning electron microscopy,
      Fourier transform infrared analysis, thermogravimetric analysis, X-ray
      diffraction, and vibrating magnetometer, which indicated that ILMPM had a
      regularly spherical shape and strong magnetic property. The obtained ILMPM were
      successfully applied as a special adsorbent of magnetic dispersive solid phase
      extraction (MDSPE) for the rapid extraction and isolation of sulfamonomethoxine
      sodium and sulfachloropyrazine sodium in urine. The factors that affected
      extraction efficiency, such as adsorption conditions, desorption conditions,
      washing and elution solvents, and pH of the sample solution, were optimized.
      Under the optimum condition, good linearity in the range of 0.005-2.0 MUg g(-1)
      (r >= 0.9996) was obtained for the two sulfonamides (SAs); the average recoveries
      at three spiked levels ranged from 86.9 to 102.1 %, with relative standard
      deviations of <=4.3 %. The presented ILMPM-MDSPE method combined the advantages
      of ILs, MNPs, and MDSPE and therefore could be potentially applied for rapid
      screening of SAs in urine.

PMID- 24573581
TI  - [What cares to be taken before surgery? Informed consent every time?].

PMID- 24573580
TI  - Development and validation of a LC/TOF MS method for the determination of
      carboplatin and paclitaxel in nanovesicles.
AB  - Carboplatin and paclitaxel co-loaded nanovesicles (CPT-PTX-CLV), a novel
      intravenous formulation void of cremophor EL, may have significant advantages
      over conventional carboplatin and paclitaxel formulations with respect to tumor
      targeting, sustained drug release, reduced toxicity, and synergistic efficacy
      profiles. The aim of this study was to develop and validate a rapid, specific,
      sensitive, and reliable liquid chromatography-time of flight-mass spectrometry
      (LC/TOF MS)-based bioanalytical method for the simultaneous quantification of CPT
      and PTX in a fetal bovine serum (FBS) vehicle containing the dispersed
      nanovesicles. The analytes were extracted from FBS by simple protein
      precipitation, with subsequent separation of CPT and PTX on a Waters HPLC SunFire
      C18 column at a flow rate of 0.25 ml/min using gradient elution mode. The total
      analytical time was only 12 min. Detection and quantitation was performed by
      electrospray ionization (ESI) in the positive ionization mode with selective ion
      monitoring (SIM) at m/z 310.0152 for CPT and 876.3224 for PTX. The calibration
      curves were linear over the concentration range of 10-4,000 ng/ml for CPT and 5
      2,000 ng/ml for PTX (r (2)  > 0.99), with the respective lower limit of
      quantification (LLOQ) at 10 and 5 ng/ml. The intra- and inter-day precision and
      accuracy of analysis of the quality control samples at low, medium, and high
      concentration levels were <=13.6 % relative standard deviation (RSD) and <=14.6 %
      relative errors (RE). The rapid, sensitive, and reproducible LC/TOF MS method may
      be used to support preclinical and clinical pharmacological studies of the CPT
      PTX-CLV administered by injection in animal and human cancer models.

PMID- 24573582
TI  - Impact of intraoperative transesophageal echocardiography in mortality in
      coronary artery bypass grafting.
AB  - OBJECTIVE: To evaluate the rates of mortality and morbidity in patients
      undergoing coronary artery bypass grafting (CABG) with cardiopulmonary bypass
      (CPB) using routine intraoperative transesophageal echocardiography (ITEE).
      METHODS: We conducted a retrospective, observational review of medical records of
      360 patients from April 2010 to April 2012. We analyzed: age, weight, height,
      gender, EuroSCORE, diabetes mellitus, ejection fraction and number of diseased
      vessels. Outcomes were compiled in intraoperative and postoperative (myocardial
      infarction, stroke, renal failure, hemodialysis, atrial fibrillation, length of
      stay in the intensive care unit). RESULTS: 53 patients were included, with 27
      receiving monitoring; we excluded 307 individuals, as they were not operated by
      the same surgical team. The two groups were homogeneous for age, weight and
      gender. However, the ejection fraction was lower in the group submitted to ITEE
      (ITEE group 56.3% versus Non-ITEE group 65.9 +/- 11%, p = 0.01). In patients not
      subjected to ITEE, mortality was higher (ITEE group 0% versus Non-ITEE group
      7.6%, p = 0.01). There was no significant difference between groups as for the
      incidence of stroke, myocardial infarction, atrial fibrillation and acute kidney
      injury. CONCLUSION: The use of intraoperative transesophageal echocardiography in
      patients undergoing coronary artery bypass grafting with cardiopulmonary bypass
      decreased perioperative mortality, warranted the use of inotropic drugs and
      vasodilators and contributed to a better patient outcome.

PMID- 24573583
TI  - Predictors of major postoperative complications in neonatal surgery.
AB  - OBJECTIVE: To investigate the incidence and severity of early postoperative
      complications and to identify their risk factors in newborns undergoing surgery
      under general anesthesia. METHODS: We conducted a retrospective analysis of data
      from 437 critically ill newborns undergoing surgery in a tertiary pediatric
      surgical center, between January 2000 and December 2010. Complications that
      occurred within the first 30 days after surgery were classified using the Clavien
      Dindo system, for which grades III to V were considered severe. We used
      univariate and multivariate analysis to evaluate pre- and intraoperative
      variables potentially predictive of severe postoperative complications. RESULTS:
      The incidence of at least one serious complication was 23%, with a median of one
      complication per patient 1:3. Altogether, there were 121 serious complications.
      Of these, 86 required surgical, endoscopic or radiological interventions (grade
      III), 25 endangered life, with uni or multi-organ failure (grade IV) and ten
      resulted in death (grade V). The most common complications were technical (25%),
      gastrointestinal (22%) and respiratory (21%). We identified four independent risk
      factors for severe postoperative complications: reoperation, operation for
      congenital diaphragmatic hernia, preterm birth less than 32 weeks of gestational
      age and abdominal surgery. CONCLUSION: The incidence of severe postoperative
      complications after neonatal surgeries under general anesthesia remains high. The
      conditions considered independent risk factors for those can guide interventions
      to improve results.

PMID- 24573584
TI  - Results of the simultaneous bilateral inguinal hernia repair by the Lichtenstein
      technique.
AB  - OBJECTIVE: To analyze the results of bilateral inguinal hernia repairs by the
      Lichtenstein technique. METHODS: We studied the charts of 59 patients who
      underwent elective simultaneous bilateral inguinal hernia repair between 2003 and
      2007. We analyzed: gender, age, weight, operative time, length of hospital stay,
      Nyhus classification, complications in the immediate and late postoperative
      periods, and recurrence. These data were submitted to descriptive statistical
      analysis. RESULTS: Of the 59 patients, 95% were men. Age ranged from 40 to 60
      years; weight, from 50 to 103 kg; operative time, from 60 to 80 minutes; and the
      length of stay, from one to six days. Thirty patients had type IIIB hernias;
      nine, type II; ten, type IIIA; seven, type IV; one, type II on the left and type
      IIIB on the right; one, type IIIA on the right and IIIB on the left; and one,
      type IIIA on the right and type II on the left. In the immediate postoperative
      period, pain was the most important manifestation, in 30.5% of subjects. In
      94.92% of cases there were no complications. There were two cases of inguinodinia
      and one of burning pain in the surgical site. There was one recurrence 29 months
      after the procedure. CONCLUSIONS: Simultaneous bilateral inguinal hernia repair
      by Lichtenstein technique was safe and effective, with a low rate of
      complications, short hospital stay, and only one case of recurrence at an average
      of 48 months follow-up.

PMID- 24573585
TI  - Inguinal hernias in patients of 50 years and above. Pattern and outcome.
AB  - OBJECTIVE: to evaluate a one year experience with inguinal hernia repair, in
      patients of > 50 years, with respect to the type of inguinal hernia, type of
      surgery, postoperative complications and recurrence. METHODS: a prospective
      descriptive study of patients (n=57) > 50 years operated for inguinal hernia
      during a one year period. Tension-free meshplasty and herniorrhaphy, using 3"x6"
      polypropylene mesh and 2-0 polypropylene suture, were performed in elective and
      emergency surgery respectively. Follow-up visits were scheduled at six weeks,
      three and six months postoperatively. RESULTS: the most representative age group
      was 61-70 years, and all patients were male. 52 (91.22%) patients had unilateral
      inguinal hernias, while five (8.77%) had bilateral hernias. In 50 (87.71%)
      patients, the hernia was uncomplicated, while seven (12.28%) patients presented
      with some complication such as obstruction or strangulation. Elective surgery was
      performed in 50 (87.71%) patients while seven (12.28%) patients were operated in
      emergency. Postoperatively, 50 (87.7%) patients had uneventful recovery, while
      seven (12.28%) patients developed some complications which were treated
      conservatively. Mean hospital stay was six days. One recurrence was observed and
      there was no peri/postoperative death. CONCLUSION: tension-free meshplasty and
      herniorrhaphy are safe, simple and applicable even in elderly patients after
      adequate pre-operative assessment and optimization. Although associated with
      longer hospital stay, the mortality rate is nil and complication as well as
      recurrence rate is low. Hence, timely repair is necessary in elderly patients
      even in those with comorbid conditions.

PMID- 24573586
TI  - Evaluation of the venous reflux of the great saphenous vein by duplex scan after
      surgical treatment of the saphenofemoral junction insufficiency.
AB  - OBJECTIVE: To evaluate the occurrence of reflux from the great saphenous vein by
      color Doppler ultrasonography in subjects undergoing treatment of insufficiency
      of the saphenofemoral junction by simple ligation or ligation with section of the
      saphenous arch. METHODS: We performed 60 operations (in 45 subjects) of varicose
      insufficiency of the saphenofemoral junction (SFJ), belonging to the CEAP
      clinical classification of 2-5, who were randomly divided into two groups. A
      group called C, with ligature and section of the saphenous arch, and a group
      called L, with simple ligation of the saphenous vein and no sectioning of its
      arch. We then investigated the occurrence of reflux from the great saphenous vein
      in groups C and L through postoperative color Doppler ultrasonography at
      intervals of six months to one year. RESULTS: Of the 60 members submitted to the
      approach of the saphenous arch, 57 were evaluated by postoperative doppler
      ultrasound, since two subjects (three limbs) did not return and were excluded
      from the study. The mean age was 54 years, with 93% females and predominance of
      CEAP classification 2 in 60.5%. Of the 57 operations for the treatment of reflux
      of the saphenous arch, 43.9% had reflux postoperatively,14.1% in group C and
      29.8% in group L (p < 0,05). The relative risk of reflux of the saphenous arch in
      group L was 2.03 times higher compared with group C. CONCLUSION: the section of
      the arch of the great saphenous vein causes less postoperative reflux than simple
      ligation in treatment of insufficiency of the great saphenous vein.

PMID- 24573587
TI  - Uterine artery embolization with spherical PVA-PVAc particles as preparation for
      surgical resection of myomas.
AB  - OBJECTIVE: To evaluate the use of a new spherical particle of polyvinyl alcohol
      and polyvinyl acetate (PVA-PVAc) for uterine artery embolization in patients with
      myoma with surgical indication. METHODS: twelve patients underwent uterine myoma
      embolization with PVA-PVAc particles. Three to nine months later, they were
      submitted to laparotomy with myomectomy. We analyzed the following parameters:
      volume of the uterus and of the bigger myoma; concentrations of follicle
      stimulating hormone and hemoglobin; menstrual bleeding (number of days and used
      absorbents), signs and symptoms before treatment, after embolization and after
      myomectomy. RESULTS: The mean age was 37 years and mean uterine volume prior to
      treatment, 939.3 cc. Three years after embolization, there was reduction in
      uterine volume (p = 0.0005), increase in hemoglobin concentration after
      embolization (p = 0.0004), without variation after the myomectomy. There was no
      significant variation of the follicle stimulating hormone (p = 0.17). There was
      no case of ovarian failure, but one of the patients had endometrial atrophy. Two
      patients became pregnant, with good obstetric indicators. Signs and symptoms
      improved after embolization, and remained after myomectomy. CONCLUSION: Arterial
      embolization with spherical PVA-PVAc particles is promising in the preparation
      for myoma surgery, since it was associated with a reduction in uterine volume,
      decrease in intraoperative bleeding and made possible the use of smaller
      incisions, increasing the chance of preserving the uterus.

PMID- 24573588
TI  - Subatmospheric pressure therapy in the treatment of traumatic soft tissue
      injuries.
AB  - OBJECTIVE: To evaluate the use of subatmospheric pressure therapy in the
      treatment of acute traumatic injuries of the soft tissues, especially in the
      limbs. METHODS: One hundred and seventy-eight patients with traumatic wounds were
      treated by the Center for Complex Wounds in the period from January 2010 to
      December 2011, and submitted to subatmospheric pressure therapy (SPT). RESULTS:
      Of the 178 patients who underwent SPT, 129 (72.5%) were male and 49 (27.5%) were
      aged between 18 and 40 years. Degloving injuries to the limbs were the most
      common type of traumatic wounds, being responsible for the hospitalization of 83
      (46.6%) patients. Mean hospital stay was 17.5 days. A total of 509 procedures
      were performed (average 2.9 per patient). SPT was used in 287 procedures, 209
      (72.8%) on traumatic wounds and 78 (27.2%) of skin grafts. The number of
      exchanges of the SPT apparel per patient was 1.6 and the mean time of use, 8.5
      days. CONCLUSION: SPT significantly reduced morbidity and healing time of
      injuries when compared with previously performed dressing treatments. The
      subatmospheric pressure therapy is a useful method in treating acute traumatic
      wounds, acting as a bridge between the emergency treatment and the final coverage
      of the skin lesions, being better when compared with more traditional methods of
      plastic surgery.

PMID- 24573589
TI  - Solid pseudopapillary tumor of the pancreatic: evaluation of clinical,
      radiological and surgical profiles.
AB  - OBJECTIVE: To describe the clinical, radiological and surgical features of solid
      pseudopapillary tumor of the pancreas. METHODS: We conducted a retrospective,
      observational study evaluating the multi-institutional clinical, radiological and
      surgical patients with a diagnosis of solid pseudopapillary tumor of the pancreas
      undergoing surgical treatment. RESULTS: We identified eight patients in three
      hospitals in the state of Amazonas, seven females, six under the age of 30. The
      neoplasia predominated in the head of the pancreas. Five patients underwent
      pancreaticoduodenectomy, one enucleation, one distal pancreatectomy, and one was
      considered unresectable. CONCLUSION: Solid pseudopapillary tumor of the pancreas
      predominated in young female patients, predominantly located in the pancreatic
      head.

PMID- 24573590
TI  - Complementation by argon plasma coagulation after endoscopic piecemeal resection
      of large colorectal adenomas.
AB  - OBJECTIVE: To evaluate the efficacy of complement by argon plasma coagulation to
      reduce the rate of residual or recurrent tumor after complete endoscopic
      piecemeal resection of large sessile colorectal adenomas. METHODS:  INCLUSION
      CRITERIA: patients with large sessile colorectal adenomas (e" 20 mm), without
      morphological signs of deep infiltration, submitted to complete endoscopic
      piecemeal resection studied with chromoendoscopy and magnification of images.
      Patients were randomized into two groups: group 1 - no additional procedure, and
      group 2 - complementation by argon plasma coagulation. follow-up colonoscopy was
      performed at three, six and 12 months postoperatively. We evaluated the rate of
      local recurrence or residual malignancy. RESULTS: The study included 21 patients,
      eleven in group 1 and ten in group 2. There were two local recurrences or
      residual tumors in each group, detected at three months follow-up. CONCLUSION:
      Complementation by argon plasma coagulation after apparent complete endoscopic
      piecemeal resection of large sessile colorectal adenomas does not seem to reduce
      the occurrence of residual adenomatous lesions or local recurrence.

PMID- 24573592
TI  - Mechanical cervical esophagogastric laterolateral anastomosis after
      esophagectomies.
AB  - Among the challenges of esophagectomies, the cervical anastomosis remains
      challenging for its consequences, the main being the anastomotic stricture. The
      authors present a technique for an Orringer-fashion mechanical cervical
      laterolateral esophagogastric anastomosis, which reduces the rate of fistula and
      stenosis. 

PMID- 24573591
TI  - Surgeons' knowledge and attitude regarding concepts of nutritional therapy.
AB  - OBJECTIVE: To compare the knowledge of nutritional therapy (NT) of surgery
      residents and surgeons. METHODS: We applied two standardized questionnaires on
      knowledge, attitude and behavior regarding NT to 50 physicians (35 residents and
      15 surgeons) of 12 different surgical areas. We compared the proportions of hits
      according to the perception on the subject of each group using the Fisher exact
      test, with 5% significance and p < 0.05. RESULTS: More than 80% did not feel safe
      regarding NT and 46% denied knowledge of the NT multidisciplinary team (NTMT).
      There was a higher percentage of correct answers among residents in the items:
      surgical trauma and its nutritional influence on the patient (p = 0.047); normal
      BMI (p = 0.036); preoperative NT (p = 0.007); and indication of preoperative NT
      in the group that referred that to interact with the NTMT (p = 0.02). Among
      surgeons: complications of NT and NT in previously malnourished patients (p =
      0.044); and methods for assessing preoperative nutritional status in the group
      that referred to interact with the NTMT (p =0.01). CONCLUSION: there are gaps in
      medical education. Only 13.3% were confident about NT, and their knowledge did
      not justify such confidence. There were no differences between the successes of
      confident and non-confident about NT in most subjects. The best results came from
      the group that claimed to be assisted by any NTMT. Better medical educational
      programs should be goal for this university.

PMID- 24573594
TI  - [Forequarter amputation under locoregional anesthesia].
AB  - Forequarter amputations are an uncommon option for the treatment of upper limb
      and shoulder girdle tumors nowadays. This procedure can be done by different
      approaches and general anesthesia is commonly used. The authors report a case of
      forequarter amputation by the posterior approach performed for treatment of a
      soft-tissue sarcoma under a brachial plexus block associated with venous sedation
      and local anesthesia. 

PMID- 24573593
TI  - The use of corticosteroid for the prophylaxis of fat embolism syndrome in
      patients with long bone fracture.
AB  - The "Evidence-based Telemedicine - Trauma & Acute Care Surgery" (EBT-TACS)
      Journal Club conducted a critical review of the literature and selected three
      recent studies on the use of corticosteroids for the prophylaxis of fat embolism
      syndrome. The review focused on the potential role of corticosteroids
      administration to patients admitted to the intensive care unit (ICU) at risk of
      developing post-traumatic fat embolism. The first study was prospective and aimed
      at identifying reliable predictors, which occurred early and were associated with
      the onset of fat embolism syndrome in trauma patients. The second manuscript was
      a literature review of the role of corticosteroids as a prophylactic measure for
      fat embolism syndrome (FES). The last manuscript was a meta-analysis on the
      potential for corticosteroids to prophylactically reduce the risk of fat embolism
      syndrome in patients with long bone fractures. The main conclusions and
      recommendations reached were that traumatized patients should be monitored with
      non-invasive pulse oximetry and lactate levels since these factors may predict
      the development of FES, and that there is not enough evidence to recommend the
      use of steroids for the prophylaxis of this syndrome. 

PMID- 24573595
TI  - [Pyloric stenosis due to adenocarcinoma of the pylorus].
AB  - We present a case of primary malignant pylorus neoplasia, emphasizing its rarity,
      the difficulty of diagnosis and the importance of an adequate prepare before the
      endoscopic procedure. Literature shows that tumors compromising the first, third
      and fourth segments of duodenum are rare, especially those of the pyloric area,
      representing only 0.35% of all malignant tumors of the gastrointestinal tract.
      Adenocarcinoma is the most common histological type, representing 50% of all
      malignant neoplasias at this site. The most common symptoms are weight loss,
      nausea, vomiting, abdominal pain, abdominal mass, sudden changes in intestinal
      habits and iron deficiency anemia secondary to chronic intestinal hemorrhage.
      Survival after five years is only 18%. We report a case of a seventy-one year-old
      male referring early satiety, epigastric pain, retrosternal burning and
      dyspepsia, with unspecific results in complementary exams, since complete gastric
      emptying was not achieved. As symptoms worsened, the patient was submitted to
      laparotomy, with identification of gastric dilation and severe pyloric stenosis,
      macroscopically suggesting malignancy. The chosen procedure was a subtotal
      gastrectomy. Adjuvant radiotherapy and chemotherapy were not used. The patient is
      been followed-up without tumor recurrence so far. 

PMID- 24573596
TI  - Effect of habitat quality on diet flexibility in Barbary macaques.
AB  - Barbary macaques live in extreme temperate environments characterized by strongly
      seasonal resource availability. They are mainly terrestrial while foraging,
      harvesting food from the herbaceous layer. These monkeys are threatened mainly
      because of anthropogenic habitat degradation. We studied the adaptive capacities
      of wild groups of Barbary macaques that lived in different cedar forests
      undergoing varying extents of grazing pressure from domestic livestock. In all
      three sites, diet varied seasonally. Heavy grazing led to a significant decrease
      in herbaceous production and species richness. As a consequence, the monkeys'
      diet in this poor habitat showed a decreased plant species richness. Moreover, it
      incorporated fewer above-ground herbaceous resources, and a greater proportion of
      subterranean resources (especially hypogeous fungi and subterranean invertebrates
      such as earthworms, eggs and adults of earwigs, and ant's larvae) than the diet
      of monkeys inhabiting ungrazed forest. Cedar bark, cedar strobiles, earthworms,
      and earwigs were part of the monkeys' diet only in grazed forest. Monkeys in
      heavily grazed forest compensated for a lack of herbaceous foods by eating
      subterranean foods preferentially to tree and shrub products. The foods they
      consumed take longer to harvest and process than the seeds or leaves consumed by
      Barbary macaques in less heavily grazed forest habitats. Our results suggest that
      monkeys do differ in their diets according to the degree of habitat change
      induced by human activities. They also highlight the dietary flexibility of
      Barbary macaques as a key element that allows them to cope with degraded
      habitats. We later compare the dietary adjustments of Barbary macaques facing
      environmental change to dietary strategies of other macaques and temperate-zone
      primates.

PMID- 24573597
TI  - Diverse roles of miR-29 in cancer (review).
AB  - microRNAs (miRNAs) are non-coding RNAs which have the capacity to regulate gene
      expression at the post-transcriptional level, and have emerging as key factors
      involved in cancer at all stages ranging from initiation to metastasis. In the
      present review, we summmarize the diverse roles of the microRNA-29 (miR-29)
      family in cancer. First, we present a concise introduction to the miR-29 family
      and the expression profile of miR-29 in various cancer types. We next highlight
      the upstream regulatory pathway of miR-29 and describe the relationship between
      miR-29 and cancer in detail. As a tumor suppressor, miR-29 restrains cancer
      progression by promoting tumor cell apoptosis, by suppressing DNA methylation of
      tumor-suppressor genes, by reducing proliferation of tumors and by increasing
      chemosensitivity. However, as a tumor promoter, miR-29 mediates epithelial
      mesenchymal transition (EMT) and promotes metastasis in breast cancer and colon
      cancer. Finally, we suggest that miR-29 represents a novel diagnostic and
      prognostic biomarker or a therapeutic target for cancer. Our review highlights
      the diverse relationship between miR-29 and cancer (particularly digestive system
      neoplasms). Further research of miR-29 in cancer is warranted. 

PMID- 24573598
TI  - Design and evaluation of a multimedia electronic patient record "oncoflow" with
      clinical workflow assistance for head and neck tumor therapy.
AB  - OBJECTIVES: The management of patient-specific information is a challenging task
      for surgeons and physicians because existing clinical information systems are
      insufficiently integrated into daily clinical routine and contained information
      entities are distributed across different proprietary databases. Thus, existing
      information is hardly usable for further electronic processing, workflow support
      or clinical studies. METHODS: A Web-based clinical information system has been
      developed that automatically imports patient-specific information from different
      information systems. The system is tailored to the existing workflow for the
      treatment of patients with head and neck cancer. In this paper, the clinical
      assistance functions and a quantitative as well as a qualitative system
      evaluation are presented. RESULTS: The information system has been deployed at a
      clinical site and is in use in daily clinical routine. Two evaluation studies
      show that the information integration, the structured information presentation in
      the Web browser and the assistance functions improve the physician's workflow.
      The studies also show that the usage of the new information system does not
      impair the time physicians need for a process step compared with the usage of the
      existing information system. CONCLUSIONS: Information integration is crucial for
      efficient workflow support in the clinic. The central access to information
      within a modern and structured user interface saves valuable time for the
      physician. The comprehensive database allows an instant usage of the existing
      information clinical workflow support or the conduction of trial studies.

PMID- 24573599
TI  - Sex differences and laterality of insulin receptor distribution in developing rat
      hippocampus: an immunohistochemical study.
AB  - This study aimed to compare the regional distribution of insulin receptor in
      various portions of newborn rat hippocampus on postnatal days 0 (P0), 7 (P7), and
      14 (P14) between male/female and right/left hippocampi. We found that the number
      of insulin receptor (InsR)-immunoreactive-positive (InsR+) cells in CA1 continued
      to increase until P7 and remained unchanged thereafter. A marked increase in
      distribution of InsR+ cells in CA3 from P0 to P14 was observed, although there
      was a significant decline in the number of InsR+ cells in dentate gyrus (DG) at
      the same time. No differences between the right/left and male/female hippocampi
      were detected at P0 (P > 0.05). Seven-day-old female rats showed a higher number
      of labeled cells in the left than in the right hippocampus. Moreover, the
      differences between the number of InsR+ cells in area CA1 and CA3 were
      statistically significant between males and females (P < 0.05). At P14, the
      number of InsR+ cells was significantly higher in CA1 and DG of males, especially
      in the right one (P < 0.05). These results indicate the existence of a
      differential distribution pattern of InsR between the left/right and male/female
      hippocampi. Together with other mechanisms, these differences may underlie sexual
      dimorphism and left/right asymmetry in the hippocampus.

PMID- 24573600
TI  - Acetylcholinesterase complexes with the natural product inhibitors
      dihydrotanshinone I and territrem B: binding site assignment from inhibitor
      competition and validation through crystal structure determination.
AB  - Acetylcholinesterase (AChE) is a critical enzyme that regulates neurotransmission
      by degrading the neurotransmitter acetylcholine in synapses of the nervous
      system. It is an important target for both therapeutic drugs that treat
      Alzheimer's disease and organophosphate (OP) chemical warfare agents that cripple
      the nervous system and cause death through paralysis. We are exploring a strategy
      to design compounds that bind tightly at or near a peripheral or P-site near the
      mouth of the AChE active site gorge and exclude OPs from the active site while
      interfering minimally with the passage of acetylcholine. However, to target the
      AChE P-site, much more information must be gathered about the structure-activity
      relationships of ligands that bind specifically to the P-site. Here, we review
      our recent reports on two uncharged, natural product inhibitors of AChE,
      dihydrotanshinone I and territrem B, that have relatively high affinities for the
      enzyme. We describe an inhibitor competition assay and comment on the structures
      of these inhibitors in complex with recombinant human acetylcholinesterase as
      determined by X-ray crystallography. Our results reveal that dihydrotanshinone I
      binding is specific to only the P-site, while territrem B binding spans the P
      site and extends into the acylation or A-site at the base of the gorge. 

PMID- 24573601
TI  - Gabapentin enhances the morphine anti-nociceptive effect in neuropathic pain via
      the interleukin-10-heme oxygenase-1 signalling pathway in rats.
AB  - In the present study, we investigated the anti-inflammatory mechanisms by which
      gabapentin enhances morphine anti-nociceptive effect in neuropathic pain in rats
      and the interaction between the anti-nociceptive effects of gabapentin on
      morphine and the interleukin (IL)-10-heme-oxygenase (HO)-1 signal pathway in a
      rat model of neuropathic pain. The neuropathic pain model was induced via a left
      L5/6 spinal nerve ligation (SNL) in rats. The anti-nociceptive effect of
      gabapentin and IL-10 on morphine was examined over a 7-day period, and the
      effects of the anti-IL-10 and HO-1 inhibitor zinc protoporphyrin (ZnPP) on
      gabapentin/morphine co-injection were assessed. Drug administration was given
      over 7 days, and on day 8, both anti-inflammatory cytokine IL-10, a stress
      induced protein HO-1 and pro-inflammatory cytokines IL-1beta, IL-6 and TNF-alpha
      were measured. Gabapentin attenuated morphine tolerance over 7 days of co
      administration, and reduced the expression of pro-inflammatory cytokines but
      increased IL-10 and HO-1 expression. The effect of gabapentin on morphine was
      partially blocked using the anti-IL-10 antibody or the HO-1 inhibitor zinc
      protoporphyrin. Our findings indicated that the anti-nociceptive effects of
      gabapentin on morphine might be caused by activation of the IL-10-HO-1 signalling
      pathway, which resulted in the inhibition of the expression of pro-inflammatory
      cytokines in neuropathic pain in the rat spinal cord.

PMID- 24573602
TI  - Differential regulation of lipid metabolism genes in the brain of
      acetylcholinesterase knockout mice.
AB  - Mice deficient in acetylcholinesterase (AChE; EC3.1.1.7) exhibited significant
      phenotypical and biochemical changes when compared with wild-type littermates.
      They showed a delay of growth in weight and size, immature external ears, and
      persistent body tremor, and they circled when walking. The molecular mechanisms
      underlying these changes have not been investigated yet. Here, we studied the
      profiles of both the messenger RNA (mRNA) and protein expression in the brain of
      AChE-deficient mice using mRNA microarray, quantitative PCR, and two-dimensional
      difference gel electrophoresis (2D DIGE) coupled to protein identification with
      matrix-assisted laser desorption/ionization time of flight (MALDI-TOF) mass
      spectrometry. Analysis of gene expression profile was conducted by DAVID (
      http://david.abcc.ncifcrf.gov ) and Ingenuity Pathway Analysis (IPA,
      http://www.ingenuity.com ). Previous results implicated that there is a close
      relationship between lipid metabolisms which were associated with central nervous
      system development. Here, we demonstrated that the mRNA expressions of brain
      specific fatty acid protein 7 (fabp-7) and phospholipase A2 group IV (pla2g4)
      were significantly downregulated in AChE-deficient mice. These results suggested
      that AChE may play a role in neurogenesis and neurodegeneration by specifically
      regulating lipid metabolism in the brain. 

PMID- 24573603
TI  - Thromboprophylaxis for lung cancer patients--multimodality assessment of
      clinician practices, perceptions and decision support tools.
AB  - PURPOSE: The purpose of this study was to report the opinions and self-reported
      practices of clinicians, as well as the availability of decision support tools,
      regarding appropriate thromboprophylaxis for patients with lung cancer to
      identify variation in practice and/or divergence from evidence-based clinical
      practice guidelines (CPG). METHODS: A computer-generated survey (SurveyMonkey
      software) was distributed to surgical, radiation and medical oncologists with
      lung cancer specialisation, via membership of the Australian Lung Cancer Trials
      Group (ALTG) from May to September 2013. RESULTS: Seventy-two clinicians, from
      public, private, specialist and general hospitals, completed the survey (46%
      response rate). Hospital-endorsed CPG were widely available (91%); however, these
      routinely lacked robust recommendations for the ambulatory care setting (98%) and
      risk stratification tools (65%). Clinicians consistently identified ambulatory
      care treatment modalities (chemotherapy, alone or in combination with
      radiotherapy) as having similar (high) thrombotic risk as surgery. Timing and
      duration of pharmacological thromboprophylaxis prescribing among surgical
      oncologists varied and were divergent from guideline recommendations. Fifty-eight
      percent of surveyed clinicians cited a lack of high-quality data to guide
      preventative strategies in lung cancer patients. CONCLUSION: Clinicians
      consistently identified patients with lung cancer as having a high thromboembolic
      risk in both ambulatory and surgical settings, but with differences in
      recommendations and variation in practice. CPG lacked robust recommendations for
      the ambulatory care setting, the main arena for the multimodality lung cancer
      treatment paradigm.

PMID- 24573604
TI  - The experiences of participants in an innovative online resource designed to
      increase regular walking among rural cancer survivors: a qualitative pilot
      feasibility study.
AB  - PURPOSE: Physical activity has been associated with improved outcomes for cancer
      survivors. Compared to their urban counterparts, rural Australians experience a
      health disadvantage, including poorer survival rates after diagnosis of cancer.
      The aim of this pilot feasibility study was to gain insight into the experiences
      of rural cancer survivors engaging in an online resource designed to increase
      regular walking. METHODS: A 6-week online lifestyle intervention was implemented
      among eight cancer survivors living in three rural regions of South Australia.
      Participants used a pedometer to monitor daily steps taken, reported daily steps
      using a specially designed website and were provided with daily step goals based
      on their affective state. Participants took part in semi-structured face-to-face
      interviews to gauge their impressions of the program. Data were analysed using
      qualitative description and content analysis to derive major themes from the
      interviews. RESULTS: The program motivated participants to increase their walking
      and resulted in improvements in several self-reported physical and quality of
      life outcomes. The resource was clear and easy to navigate. The three-tiered step
      goal system reduced feelings of guilt if participants were unable to reach a
      goal. The step log and graph allowed participants to self-monitor their progress.
      The forum fostered social support; however, more interaction with intervention
      personnel was suggested. CONCLUSIONS: This online pedometer-based walking
      intervention is feasible and effectively increases motivation for walking and
      enhances health-related quality of life in South Australian rural cancer
      survivors. A randomized controlled trial of this intervention is warranted.

PMID- 24573605
TI  - Looking for a better creatinine.

PMID- 24573606
TI  - A SAM-dependent methyltransferase cotranscribed with arsenate reductase alters
      resistance to peptidyl transferase center-binding antibiotics in Azospirillum
      brasilense Sp7.
AB  - The genome of Azospirillum brasilense harbors a gene encoding S
      adenosylmethionine-dependent methyltransferase, which is located downstream of an
      arsenate reductase gene. Both genes are cotranscribed and translationally
      coupled. When they were cloned and expressed individually in an arsenate
      sensitive strain of Escherichia coli, arsenate reductase conferred tolerance to
      arsenate; however, methyltransferase failed to do so. Sequence analysis revealed
      that methyltransferase was more closely related to a PrmB-type N5-glutamine
      methyltransferase than to the arsenate detoxifying methyltransferase ArsM.
      Insertional inactivation of prmB gene in A. brasilense resulted in an increased
      sensitivity to chloramphenicol and resistance to tiamulin and clindamycin, which
      are known to bind at the peptidyl transferase center (PTC) in the ribosome. These
      observations suggested that the inability of prmB:km mutant to methylate L3
      protein might alter hydrophobicity in the antibiotic-binding pocket of the PTC,
      which might affect the binding of chloramphenicol, clindamycin, and tiamulin
      differentially. This is the first report showing the role of PrmB-type N5
      glutamine methyltransferases in conferring resistance to tiamulin and clindamycin
      in any bacterium.

PMID- 24573607
TI  - Bone morphogenetic protein 2 inhibits hepatocellular carcinoma growth and
      migration through downregulation of the PI3K/AKT pathway.
AB  - Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide.
      Previous studies have suggested that abnormal expression of BMP-4, BMP-7, and BMP
      9 is correlated with tumor progression in HCC, but the role played by BMP-2 in
      HCC has not yet been reported. To determine the role of BMP-2 in HCC, we first
      investigated the effect of exogenous BMP-2 on the growth of the cell lines HCC SK
      Hep-1, Hep G2, and Hep 3B. Next, we studied the function of BMP-2 in SK-Hep-1 HCC
      cell line using a recombinant lentivirus vector to deliver BMP-2. We also used
      siRNA to silence endogenous BMP-2 expression in the HCC Hep 3B cell line. Then,
      cell growth and migration were assayed in vitro using WST-8, wound-healing, and
      transwell invasion assays. Cellular apoptosis and cell-cycle distribution were
      assessed using flow cytometry. We also investigated the effects of BMP-2
      overexpression and knockdown on the expression of proliferating cell nuclear
      antigen (PCNA), matrix metallopeptidase-2 (MMP-2), phosphorylated AKT (p-AKT),
      phosphoinositide 3-kinase p85alpha (PI3Kp85alpha), Bax, Bcl-2, caspase-3, cleaved
      caspase-3, p21, and cyclin E. As a result, we observed that BMP-2 inhibited the
      proliferation of HCC cells. Furthermore, HCC cell proliferation and migration
      were significantly diminished by BMP-2 overexpression, as was indicated by WST-8,
      would healing, and transwell assays, while knockdown of BMP-2 led to an increase
      in proliferation and migration of Hep 3B cells. BMP-2 overexpression
      significantly increased the susceptibility of SK-Hep-1 cells to low-serum-induced
      apoptosis, while BMP-2 knockdown reduced the susceptibility of Hep 3B cells.
      Overexpression of BMP-2 induced G1 phase arrest through upregulation of p21. When
      BMP-2 expression was elevated in SK-Hep-1 cells, the expression of PI3Kp85alpha,
      p-AKT, PCNA, and MMP-2 declined. These results suggest that BMP-2 exerts an
      inhibitory effect on the growth and migration of HCC cells, possibly via a
      blockade of PI3K/AKT signaling. 

PMID- 24573610
TI  - Abstracts of the ISOBM Congress 2014, 15-18 March 2014, Barcelona, Spain.

PMID- 24573611
TI  - E-cadherin expression and prognosis of oral cancer: a meta-analysis.
AB  - This study aims to evaluate the association of E-cadherin expression with the
      prognosis of oral squamous cell carcinoma (OSCC). Literature retrieval, selection
      and assessment, data extraction, and meta-analyses were performed according to
      the Revman 5.0 guidelines. In the meta-analysis, we utilized either fixed effects
      or random effects model to pool the HR according to the test of heterogeneity. A
      total of nine eligible studies included 973 OSCC patients were analyzed. Of the
      patients, 76.3 % had low expression of E-cadherin according to the cutoff value
      defined by the authors. The pooled hazard ratio (HR) of low expression of E
      cadherin for overall survival (OS) was 0.65 (95 % CI 0.52 to 0.80, P<0.001); in
      Asian population, the HR for overall survival of the patients with reduced
      expression of E-cadherin was 0.84 (95 % CI 0.75 to 0.95, P=0.006), and in non
      Asian population, the HR for overall survival of the patients with reduced
      expression of E-cadherin was 0.54 (95 % CI 0.41 to 0.69, P<0.001). Patients with
      reduced expression of E-cadherin appear to have a poorer OS compared with those
      with normal or higher expression of E-cadherin.

PMID- 24573612
TI  - Outcome of patients with cardiac resynchronisation defibrillator therapy and a
      follow-up of at least five years after implant.
AB  - QUESTIONS UNDER STUDY: Cardiac resynchronisation therapy with defibrillator
      backup (CRT-D) is an established therapeutic option in selected heart failure
      patients. Data on its pronounced long-term outcome are scarce. We evaluated the
      long-term outcome (>5 years) of patients with the main focus on device-associated
      events. METHODS: Out of a prospective CRT-D registry with 219 patients, all 49
      patients (22%) who survived for at least 5 years were analysed. Baseline
      characteristics, device associated issues (battery longevity, lead problems,
      phrenic nerve stimulation, infections and pacing threshold levels), implantable
      cardioverter-defibrillator (ICD) therapies, mortality, changes in left
      ventricular ejection fraction (LVEF) and improvement in New York Heart
      Association (NYHA) class were considered. RESULTS: The mean +/- standard
      deviation age of the patients was 63+/-10 years and follow-up was 84+/-18 months.
      Seventy-eight percent were male, 73% had nonischaemic cardiomyopathy and 80% a
      primary prevention indication. After initially surviving 5 years, 8 patients
      (16%) died during further follow-up. LVEF improved from 23%+/-7% to 35%+/-13% (p
      value <0.0001) at last follow-up. 14 patients (29%) had appropriate ICD therapy,
      mainly for ventricular tachycardia. No first-ever arrhythmic event occurred
      beyond year 4.5. Device longevity was 54+/-13 months. Twenty-three technical
      problems occurred in 20 patients (40%), 14 of whom (61%) required surgery (7 lead
      defects, 4 dislodgments, 3 others). Dislodgements occurred early (after 2+/-2
      months); defects were scattered (2-59 months) during follow-up. CONCLUSION:
      Selected patients who survive for at least 5 years experience sustained
      improvement in LVEF and NYHA- class and only few arrhythmic episodes. Technical
      problems occur in 40% of patients (60% requiring surgery), mainly shortly after
      implant and again after 4 to 5 years.

PMID- 24573614
TI  - Somatic GATA5 mutations in sporadic tetralogy of Fallot.
AB  - Tetralogy of Fallot (TOF) is the most common form of cyanotic congenital heart
      disease, with high morbidity and mortality rates. Accumulating evidence has
      demonstrated that genetic defects play an important role in the pathogenesis of
      TOF. However, the molecular basis of TOF in the majority of patients remains to
      be determined. In the present study, sequence analysis of the coding exons and
      exon-intron boundaries of GATA5, a gene encoding a zinc finger-containing
      transcriptional factor crucial for cardiogenesis, was performed on genomic DNA
      isolated from resected cardiac tissue and matched blood samples of 85 unrelated
      patients who underwent surgical repair of TOF. Genotyping was performed on the
      cardiac tissue and matched blood samples from 63 unrelated patients who underwent
      cardiac valve replacement due to rheumatic heart disease as well as the blood
      samples obtained from 200 unrelated healthy individuals. The functional effect of
      the mutations was evaluated by using a luciferase reporter assay system. As a
      result, the novel heterozygous GATA5 mutations, p.D203E and p.Y208X, were found
      in the cardiac tissues of two TOF patients, respectively. There were no mutations
      in the cardiac tissues obtained from 63 patients with rheumatic heart disease nor
      in the blood samples obtained from the 348 subjects. Functional analysis revealed
      that the GATA5 mutants were consistently associated with significantly decreased
      transcriptional activity compared with their wild-type counterpart. Thus, results
      of this study showed an association of somatic GATA5 mutations with TOF,
      providing further insight into the underlying molecular mechanism of TOF.

PMID- 24573615
TI  - On the accuracy of the GIAO-DFT calculation of 15N NMR chemical shifts of the
      nitrogen-containing heterocycles--a gateway to better agreement with experiment
      at lower computational cost.
AB  - The main factors affecting the accuracy and computational cost of the gauge
      independent atomic orbital density functional theory (GIAO-DFT) calculation of
      (15)N NMR chemical shifts in the representative series of key nitrogen-containing
      heterocycles--azoles and azines--have been systematically analyzed. In the
      calculation of (15)N NMR chemical shifts, the best result has been achieved with
      the KT3 functional used in combination with Jensen's pcS-3 basis set (GIAO-DFT
      KT3/pcS-3) resulting in the value of mean absolute error as small as 5 ppm for a
      range exceeding 270 ppm in a benchmark series of 23 compounds with an overall
      number of 41 different (15)N NMR chemical shifts. Another essential finding is
      that basically, the application of the locally dense basis set approach is
      justified in the calculation of (15)N NMR chemical shifts within the 3-4 ppm
      error that results in a dramatic decrease in computational cost. Based on the
      present data, we recommend GIAO-DFT-KT3/pcS-3//pc-2 as one of the most effective
      locally dense basis set schemes for the calculation of (15)N NMR chemical shifts.

PMID- 24573616
TI  - ortho-Benzoxylation of N-alkyl benzamides with aromatic acids catalyzed by
      ruthenium(II) complex.
AB  - A highly regioselective ortho-benzoxylation of N-alkyl benzamides with aromatic
      acids in the presence of [{RuCl2(p-cymene)}2], AgSbF6 , and (NH4)2S2O8 in 1,2
      dichloroethane at 100  degrees C for 24 h affording ortho-benzoxylated N-alkyl
      benzamides by C-H bond activation is described. Further, Ru-catalyzed
      alkenylation is done at the ortho C-H bond of benzoxylated N-alkyl benzamides
      with alkenes in water solvent. Subsequently, the benzoxyl moiety of N-alkyl
      benzamides was converted into a hydroxyl group in the presence of base or acid. A
      possible reaction mechanism was proposed to account for the present coupling
      reaction.

PMID- 24573617
TI  - [Levao Bogossian, the fomenter of scientific surgery].

PMID- 24573618
TI  - [Background on hernias].

PMID- 24573608
TI  - Genetic unraveling of colorectal cancer.
AB  - Colorectal cancer is a common disease in both men and women (being the third most
      common cancer in men and the second most common among women) and thus represents
      an important and serious public health issue, especially in the western world.
      Although it is a well-established fact that cancers of the large intestine
      produce symptoms relatively earlier at a stage that can be easily cured by
      resection, a large number of people lose their lives to this deadly disease each
      year. Recent times have seen an important change in the incidence of colorectal
      cancer in different parts of the world. The etiology of colorectal cancer is
      multifactorial and is likely to involve the actions of genes at multiple levels
      along the multistage carcinogenesis process. Exhaustive efforts have been made
      out in the direction of unraveling the role of various environmental factors,
      gene mutations, and polymorphisms worldwide (as well as in Kashmir-"a valley of
      gastrointestinal cancers") that have got a role to play in the development of
      this disease so that antitumor drugs could be developed against this cancer,
      first, and, finally, the responsiveness or resistance to these agents could be
      understood for combating this global issue. 

PMID- 24573619
TI  - Reducing accidents related to excessive alcohol intake? A retrospective study of
      polytraumatized patients undergoing surgery at a Brazilian University Hospital.
AB  - OBJECTIVE: To assess whether the Brazilian Driving Dry Law reached its goal after
      the three years following its enactment. METHODS: We conducted a retrospective
      study of patients with craniofacial fractures who underwent surgery at a
      university hospital in two periods: before the Law (2005 to 2008) and after the
      Law (2008 to 2011). RESULTS: 265 patients (220 men and 45 women) were operated on
      during this period, 149 (56%) before and 116 (44%) after the Law, which indicates
      a reduction in the number of traumatisms (p=0.04). The age range between 19 and
      40 years predominated in both periods. The main causes of traumas were car
      accidents, physical aggression and falls. Alcohol abuse was identified in 15.4%
      patients before and 19% patients after the enactment. The jaw and the maxillo
      zygomatic complex were the most affected bones. CONCLUSION: The drop in the
      number of polytraumatized patients operated on at this institution in the three
      years following the Driving Dry Law was 22%, which is below the expected and
      desired percentage. These results must be compared to those of different services
      offering the same attendance type in order to compile data and enlarge
      statistics. The low index of reduction in the number of traumatisms and the
      report of alcohol abuse by several patients at the moment of trauma, even after
      the law, evidence the need of adopting stricter measures to control and punish
      violators.

PMID- 24573620
TI  - Incidence of surgical site infection with pre-operative skin preparation using
      10% polyvidone-iodine and 0.5% chlorhexidine-alcohol.
AB  - OBJECTIVE: To analyze the incidence of surgical site infection when the
      preoperative skin preparation was performed with 10% povidone-iodine and 0.5%
      chlorhexidine-alcohol. METHODS: We conducted a randomized, longitudinal study
      based on variables obtained from patients undergoing clean and potentially
      contaminated operations. Those involved were divided into two groups. In group 1
      (G1) we included 102 patients with skin prepared with povidone-iodine, and in
      group 2 (G2), 103, whose skin was prepared with chlorhexidine. In the third,
      seventh and 30th postoperative days we evaluated the surgical site, searching for
      signs of infection. RESULTS: Data related to clinical profile, such as diabetes
      mellitus, smoking, alcoholism, haematological data (Hb, VG and leukocytes), age
      and gender, and the related variables, such as number of days of preoperative
      hospitalization, shaving, topography of incision, antibiotic prophylaxis and
      resident participation in the operation were not predisposing factors for
      surgical site infection. Two patients in G1 and eight in G2 undergoing clean
      operations had some type of infection (p = 0.1789), five in G1 and three in G2
      undergoing potentially contaminated operations had some type of infection (p =
      0.7205). CONCLUSION: The incidence of surgical site infection in operations
      classified as clean and as potentially contaminated for which skin preparation
      was done with 10% povidone-iodine and 0.5% chlorhexidine-alcohol was similar.

PMID- 24573621
TI  - Surgical treatment of skin carcinomas in the Brazilian Unified Health System:
      costs analysis.
AB  - OBJECTIVE: To analyze the costs of the surgical treatment of cutaneous carcinomas
      held in the Plastic Surgery service at a university hospital in patients of the
      Unified Health System (SUS). METHODS: we included seventy-one patients recorded
      their demographic and operation data. For analysis of direct costs we considered
      the period of patient hospitalization, including human and material costs.
      RESULTS: The average equipment cost per procedure was R$ 324.70, and the mean
      cost of hospital service, according to the table of SUS, was R$ 193.66. Thus, we
      obtained an average total cost of R$ 518.36 per procedure. However, the average
      amount refunded by the SUS per hospital procedure was R$ 429.19. CONCLUSION:
      Surgical treatment of cutaneous carcinomas generated for the hospital an average
      deficit of R$ 89.16 per procedure.

PMID- 24573622
TI  - Long-term quality of life after vertical sleeve gastroplasty.
AB  - OBJECTIVE: To evaluate the quality of life in patients undergoing vertical sleeve
      gastroplasty. METHODS: We conducted a historical cohort study including patients
      with morbid obesity the in the Unified Health System (SUS), registered in the
      database of the General University Hospital, University of Cuiaba. All patients
      underwent vertical sleeve gastroplasty and were followed for at least one year
      after the operation. The study variables were: quality of life, weight loss,
      improvement of hypertension and diabetes, and mortality. RESULTS: The sample
      comprised 41 patients, 13 (31.7%) men and 28 (61.3%) women, mean age was 37
      years, the average weight was 136.4 kg and mean BMI 50.3 kg/m2; mean follow-up
      was 19.1 months (12-32). There was a significant reduction in weight (96.7 kg, p
      < 0.001) and BMI (35.835 kg/m2, p < 0.001). The rate of blood pressure decreased
      from 56% to 31.7%, and diabetes from 14.6% to 4.8% (p < 0.001). Quality of life
      improved in 92.5% of patients. CONCLUSION: There was an improvement in the
      quality of life in the majority of patients, achieved by means of weight loss and
      clinical improvement of diabetes and hypertension.

PMID- 24573623
TI  - Surgical gastrostomy: current indications and complications in a university
      hospital.
AB  - OBJECTIVE: To analyze the surgical gastrostomies performed at a public University
      Hospital, their indications and complications. METHODS: We conducted a
      retrospective, nonrandomized review of medical records of patients who underwent
      surgical gastrostomy from 2007 to 2011; RESULTS: , In the period of studied, 86
      patients underwent surgical gastrostomies for enteral nutrition. The Stamm
      technique was employed in all cases. Men constituted 76 (88%) of the cases and
      the mean age was 58.4 years, the maximum age being 87 years and the minimum 19.
      We observed 16 (18.60%) minor complications, 17 (19.76%) serious complications
      and 8 (9.3%) perioperative deaths. CONCLUSION: Surgical gastrostomy, while
      considered a smaller procedure, is not without complications and mortality. The
      Stamm technique, despite the complications reported, is easy to perform and to
      handle, as well as safe.

PMID- 24573624
TI  - Lymph node ratio predicts tumor recurrence in stage III colon cancer.
AB  - OBJECTIVE: To evaluate the lymph node ratio as a predictor for tumor recurrence
      in stage III colon cancer patients. METHODS: Patients with stage III colon cancer
      who underwent curative resection between January 2005 and December 2010 were
      retrospectively reviewed. The main outcomes were tumor recurrence and death. The
      impact of lymph node ratio and other clinicopathological factors on disease-free
      survival were evaluated by uni- and multivariate analysis. Receiver operator
      characteristic (ROC) analysis was conducted in order to identify the best cutoff
      value for lymph node ratio to predict tumor recurrence. Disease-free survival was
      estimated by the Kaplan-Meier method. RESULTS: Seventy patients were included in
      the study (50% male). The mean age was 64 years. Univariate analysis identified
      four factors for tumor recurrence: carcinoembryonic antigen, N stage, number of
      positive lymph nodes and lymph node ratio. Lymph node ratio was the one with the
      greatest magnitude of association. Receiver operator characteristic analyzes
      identified 0.15 as the best cutoff value. Patients with a lymph node ratio < 0.15
      had a disease-free survival of 90% in 3 years (versus 64%, p = 0.011).
      CONCLUSION: Lymph node ratio is a strong predictor for tumor recurrence in stage
      III colon cancer.

PMID- 24573625
TI  - Analysis of PTEN gene by fluorescent in situ hybridization in renal cell
      carcinoma.
AB  - OBJECTIVE: To evaluate the frequency of deletion of the PTEN gene in renal cell
      carcinoma (RCC) and its impact on the rates of overall and disease-free survival.
      METHODS: We analyzed 110 patients with renal cell carcinoma who underwent radical
      or partial nephrectomy between 1980 and 2007. In 53 cases it was possible to
      analyse the PTEN gene by the method of fluorescent in situ hybridization using
      the technique of tissue microarray. For statistical analysis, patients were
      classified in two groups according to the presence or absence of the deletion.
      RESULTS: The mean follow-up time was 41.9 months. Hemizygous deletion was
      detected in 18 patients (33.9%), while the homozygous one was present in three
      (5.6%). Deletion was present in approximately 40% of the analyzed cases. Monosomy
      and trisomy were detected in nine (17%) and two patients (3.8%), respectively. In
      21 patients (39.6%) the analysis of the PTEN gene by in situ hybridization was
      normal. There were no statistically significant differences in overall (p =
      0.468) and disease-free (p = 0.344) survival rates between patients with or
      without deletion. Factors which were independent for overall survival: TNM
      clinical stage, symptoms at diagnosis, high Fuhrmann grade, performance status
      (ECoG) and tumor recurrence. Disease-free survival was influenced only by the
      clinical TNM stage. CONCLUSION: Deletion of the PTEN gene in RCC was detected
      with a frequency of approximately 40% and its presence was not determinant of
      lower survival rates, the traditional prognostic factors remaining as
      determinants of outcome.

PMID- 24573627
TI  - Guanylate cyclase inhibition by methylene blue in circulatory shock caused by
      acute necrotizing pancreatitis: a word of caution based on a porcine model.
AB  - OBJECTIVE: To study the therapeutic application of guanylate cyclase inhibition
      by methylene blue in an experimental model of acute pancreatitis in pigs.
      METHODS: acute necrotizing pancreatitis was induced in anesthetized pigs by the
      retrograde infusion of 1 ml/kg of 5% sodium taurocholate and 8 U/kg enterokinase
      in the pancreatic duct. Three groups were studied (n = 5): control (C),
      pancreatitis (AP), and MB bolus followed by pancreatitis (MB+P). The data
      included serum and abdominal fluid enzymes, hemodynamic variables, arterial
      hemogasometry, abdominal fluid volume, inflammatory markers, plasma
      nitrite/nitrate (NOx), plasma myeloperoxidase (MPO) and plasma malondialdehyde
      (MDA). One- and two-way analysis of variance (ANOVA) was performed, followed by
      the Bonferroni test (p < 0.05). RESULTS: amylase and lipase were three and 10
      fold higher in the AP group. Myeloperoxidase activity was 50% higher in the AP
      group. The hemodynamic data indicated early hypovolemic shock followed by
      cardiogenic shock. Severe fluid translocation to the peritoneal cavity was
      observed. Plasma NOx remained unchanged. The MB+P group had a five-fold increase
      in MDA compared with the C group. CONCLUSION: preemptive application of MB in
      pigs with AP demonstrated no significant effects on hemodynamic and inflammatory
      variables. The use of MB is inadequate in cases of exponential NO release, and
      extreme caution must be exercised, given the increase in lipid peroxidation based
      on the malondialdehyde dosage.

PMID- 24573626
TI  - Effects of andiroba (Carapa guianensis) oil on hepatic function of rats subjected
      to liver normothermic ischemia and reperfusion.
AB  - OBJECTIVE: To evaluate the effects of the Andiroba (carapa guianensis) oil on
      liver function in rats subjected to normothermic ischemia / reperfusion injury.
      METHODS: we divided 12 Wistar rats into two groups: saline (n = 6) and Andiroba
      (n = 6). The Andiroba group was treated with Andiroba oil (0.63 ml/kg orally) for
      seven days before surgery. Ischemia was induced by occlusion of the blood supply
      to the lateral and median lobes of the liver, using vascular clips, in both
      groups, for 45min, followed by reperfusion for 60 minutes later. We analyzed
      dosages of AST, ALT, Gamma-GT, and liver biodistribution of 99mTc phytate.
      RESULTS: There was no significant difference in the percentage of radioactivity /
      gram of tissue (%ATI/g) in the right lobe of the saline group (17.53 +/- 2.78)
      compared with the Andiroba group (18.04 +/- 3.52) p = 0.461, the same occurring
      in the%ATI/g of the left lobe of the liver when the two groups were compared (p =
      0.083). In the saline group, the%ATI/g was significantly higher in the non
      ischemic right hepatic lobe (17.53 +/- 2.78) when compared with the left lobe
      (5.04 +/- 0.82) that suffered ischemia / reperfusion (p = 0.002). Significant
      differences also occurred when comparing the right (18.04 +/- 3.52) and left
      (7.11 +/- 1.86) lobes of the animals of the Andiroba group (p = 0.004). There was
      no significant difference in dosages of AST, ALT and Gamma- GT when comparing the
      two groups (p > 0.05). CONCLUSION: Andiroba oil did not contribute to the
      protection of liver function in a rat model of liver injury induced by
      normothermic ischemia and reperfusion.

PMID- 24573629
TI  - [Defensive medicine: a necessary practice?].
AB  - We discuss the reasons why Defensive Medicine is widely used in Brazil and
      worldwide. The Defensive Medicine is characterized by excessive use of
      complementary tests, the use of supposedly safer therapeutic procedures, the
      frequent referral of patients to other specialists and by the refusal to care for
      critically ill patients and with greater potential for complications. This is a
      practice that aims to defend the doctor from legal suits. The way the processes
      are conducted by the judiciary certainly contributes to the consolidation of this
      foolish practice. The slow pace of justice in our country, associated with the
      unpreparedness of judges and legal experts in the analysis of cases, leads to an
      emotional exhaustion of the parties involved. Furthermore, poor training of
      doctors in our country values the use of sophisticated diagnostic and treatment
      methods, rather than a thorough clinical examination and appropriate
      communication with the patient. Besides inefficient in protecting the doctor,
      Defensive Medicine has severe consequences to the patient and to society, since
      it generates an additional invaluable cost to medical practice, determines
      greater suffering to the patient and causes deterioration of the doctor-patient
      relationship, which has always been marked by trust, respect and personhood. 

PMID- 24573628
TI  - [Use of panel of scientific articles on teaching of outpatient surgery].
AB  - The authors present their approach to paper selection, clinical evaluation and
      reviews as an adjunct tool to medical teaching in surgery. The panel model is
      described and discussed as an effective way to improve the learning process in a
      medical school. 

PMID- 24573630
TI  - Overweight in liver transplant recipients.
AB  - This review aims to describe the incidence and prevalence of overweight and
      obesity after liver transplantation and the consequences associated with it.
      Literature review consultation was conducted in Medline / PubMed, SciELO, EMBASE
      and LILACS, with the combination of the following keywords: liver
      transplantation, overweight, obesity, weight gain. Overweight is incident on more
      than 60% of patients undergoing liver transplantation and obesity rates exceed
      20% in the first year after surgery, during which occurs the largest relative
      weight gain. Studies have shown that between 60% and 70% of patients undergoing
      liver transplantation are overweight after the third year, 90% with abdominal
      obesity. Associated factors are, among others, advanced age, family history of
      overweight and excess weight prior to liver disease. The contribution of
      immunosuppressive medication remains controversial. Some of the consequences of
      overweight are liver steatosis, steatohepatitis, diabetes mellitus, hypertension,
      dyslipidemia, cardiovascular disease and death. 

PMID- 24573631
TI  - Management of metastatic spinal column neoplasms--an update.
AB  - The increased survival of cancer patients due to the improvement and advancement
      of therapeutic modalities has promoted progressive increase in the prevalence of
      metastatic tumors of the spine, making it important for healthcare professionals
      to acquire knowledge in the field. Spinal column metastases are usually secondary
      to malignant neoplasm of the breast, lung and prostate, male gender being the
      most often affected and pain being the initial symptom in 90% of patients. It is
      estimated that 30-90% of terminally ill patients with cancer have metastases at
      some spinal column segment. Clinical history, physical and neurological
      assessments are critical to determine the degree and extent of the lesion, and
      therefore choose the appropriate imaging method to be requested. This study aims
      to perform a review and didactic description of the main aspects related to the
      physiopathology, diagnosis and treatment of this disease. 

PMID- 24573632
TI  - Indications for head computed tomography in children with mild traumatic brain
      injury.
AB  - The "Evidence Based Telemedicine - Trauma and Emergency Surgery" (TBE-CITE)
      performed a critical appraisal of the literature and selected the three most
      relevant and recent publications on the indications for head computed tomography
      (CT) scan in pediatric patients with mild traumatic brain injury (TBI). The first
      study identified patients with mild TBI, high and low risk factors for
      intracranial injuries detected on CT scan and need for neurosurgical
      intervention. The second study evaluated the guidelines of the National Institute
      of Clinical Excellence for pediatric patients with TBI. The outcome of this study
      was either performing a head CT scan or hospital admission. The last study
      identified and analyzed the patients in whom the CT scan is not necessary and
      consequently should not be routinely indicated. Based on the critical appraisal
      of the literature and expert discussion, the opinion of the TBE-CITE was to favor
      the adoption of the PECARN guidelines, proposing CT scans for children with GCS
      of 14, altered level of consciousness and palpable skull fracture, or when the
      physician experience, multiple findings or worsening symptoms warrant it. 

PMID- 24573633
TI  - Water tuned the helical nanostructures and supramolecular chirality in
      organogels.
AB  - Water was found to tune the self-assembled nanostructures of a cationic
      amphiphile in organic solvents from nanofibers to helical tapes, helical tubes
      and chiral nanotwists with various pitch lengths depending on water content.
      Inversion of CD spectra was observed in the water-triggered polar and non-polar
      solvent gels. 

PMID- 24573634
TI  - Mountain gorilla ranging patterns: influence of group size and group dynamics.
AB  - Since the 1980s, the Virunga mountain gorilla population has almost doubled, now
      reaching 480 individuals living in a 430-km(2) protected area. Analysis of the
      gorillas' ranging patterns can provide critical information on the extent and
      possible effects of competition for food and space. We analyzed 12 years of daily
      ranging data and inter-group encounter data collected on 11 gorilla groups
      monitored by the Karisoke Research Center in Rwanda. During that period, the
      study population increased in size by almost 50% and the number of groups
      tripled. Groups had small yearly home ranges compared to other known gorilla
      populations, with an average 90% kernel density estimate of 8.07 km2 and large
      between-group variations (3.17-23.59 km2). Most groups had consistent home range
      location over the course of the study but for some, we observed gradual range
      shifts of up to 4 km. Neighboring groups displayed high home range overlap, which
      increased dramatically after the formation of new groups. On average, each group
      used only 28.6% of its 90% kernel home range exclusively, and in some areas up to
      six different groups had overlapping home ranges with little or no exclusive
      areas. We found a significant intra-group positive relationship between the
      number of weaned individuals in a group and the home range size, but the fitted
      models only explained 17.5% and 13.7% of the variance in 50% and 90% kernel home
      range size estimates, respectively. This suggests that despite the increase in
      size, the study population is not yet experiencing marked effects of feeding
      competition. However, the increase in home range overlap resulting from the
      formation of new groups led to a sixfold increase in the frequency of inter-group
      encounters, which exposes the population to elevated risks of fight-related
      injuries and infanticide.

PMID- 24573635
TI  - Effect of hypoxia on angiogenesis related factors in glioblastoma cells.
AB  - Pathological angiogenesis is a characteristic feature of glioblastoma multiforme
      (GBM) where the balance between pro-angiogenic and anti-angiogenic factors are
      shifted towards the pro-angiogenic phenotype. In this study we sought to
      determine whether angiostatins are expressed by GBM cells and whether their
      expression along with other related factors [matrix metalloproteinase (MMP)-2,
      MMP-9, and collagen type I alpha1 (COLIA1)] are altered by hypoxia and/or
      correlated with the levels of cancer stem cell marker CD133. Using qRT-PCR,
      western blotting, and gelatin zymography, we examined the expression of
      angiostatins, MMP-2, MMP-9, COLIA1 and CD133 in GBM cell lines cultured under
      aerobic conditions and hypoxia. Expression levels of MMP-2 and MMP-9 were
      significantly induced by hypoxia. Angiostatins were detected in all GBM cell
      lines and were increased by hypoxia while the angiostatin isoform of 38-kDa was
      the most abundant in GBM cells under aerobic and hypoxic conditions. COLIA1 and
      CD133 were significantly increased in several GBM cell lines under hypoxia.
      Despite expression and upregulation of anti-angiogenic factors (e.g.
      angiostatins) in GBM cells, they are overwhelmed by the overexpression of a
      larger number of angiogenic factors that shift the angiogenic balance towards the
      pro-angiogenic phenotype. Thus, an exogenous administration of anti-angiogenic
      factors may be required to improve the treatment of GBM tumors.

PMID- 24573636
TI  - Skeletal muscle metastases.

PMID- 24573637
TI  - miR-181 subunits enhance the chemosensitivity of temozolomide by Rap1B-mediated
      cytoskeleton remodeling in glioblastoma cells.
AB  - Glioblastoma multiforme (GBM) is the most malignant and frequent brain tumor,
      with an aggressive growth pattern and poor prognosis despite best treatment
      modalities. Although chemotherapy with temozolomide (TMZ) may restrain tumor
      growth for some months, TMZ resistance is also common and accounts for many
      treatment failures. Research into microRNA's role in GBM has shown that microRNAs
      play a key regulatory role in the GBM, making it a potential therapeutic target.
      In this study, we demonstrated that the lower expression of miR-181a/b/c/d
      subunits contributes to astrocytoma tumorigenesis, and their overexpression could
      inhibit the invasive proliferation of glioblastoma cells by targeting Rap1B
      mediated cytoskeleton remodeling and related molecular (Cdc42, RhoA and N
      cadherin) changes, suggesting that miR-181 was a critical regulator and might be
      an important target for glioblastoma treatment. TMZ as a standard
      chemotherapeutic agent for GBM inhibited the Rap1B expression and actin
      cytoskeleton remodeling to exert its cell killing by upregulating miR-181a/b/c/d
      subunits; conversely, each miR-181a/b/c/d subunit enhanced the chemosensitivity
      of TMZ in glioblastoma cells. 

PMID- 24573638
TI  - Detection of miR-34a and miR-34b/c in stool sample as potential screening
      biomarkers for noninvasive diagnosis of colorectal cancer.
AB  - Explore potential screening biomarkers for noninvasive diagnosis of colorectal
      cancer (CRC) by testing methylation of the miR-34a and miR-34b/c promoter in CRC
      patients' tissue and stool samples. Methylation-specific PCR analyses were
      performed on sample DNAs: 82 pairs of normal/cancer samples, 82 CRC patients'
      stool samples, 40 healthy volunteer stool samples, and 20 healthy volunteer blood
      samples were recruited. miR-34a has been found methylated in 65 of 82 (79.3%) the
      CRC tissue samples, but only 36 of 82 (43.9%) in corresponding normal samples.
      And when testing miR-34a in stool, 63 of 82 (76.8 %) CRC stool samples were
      observed methylated, and 2 of 40 (5%) healthy samples were observed methylated.
      The methylation for miR-34b/c has been found in 80 of 82 (97.5%) CRC tissue
      samples, 49 of 82 (59.8%) corresponding CRC normal samples, and 74 of 79 (93.6%)
      CRC stool samples. Yet we did not detect any methylation from healthy volunteers
      stool samples or healthy adult blood samples. Results indicated 76.8 %
      sensitivity and 93.6% specificity of the miR-34a methylation test for detecting
      CRC using stool samples. Meanwhile, the sensitivity and specificity of miR-34b/c
      were 95 and 100%, respectively. Moreover, our results revealed that abnormal DNA
      methylation of miR-34a was correlated with lymph metastasis (P = 0.010). Abnormal
      methylation of miR-34a and miR-34b/c genes might be regarded as potential
      biomarkers for noninvasive screening and diagnosis of colorectal cancer.

PMID- 24573639
TI  - Zoledronic acid treatment in advanced non-small cell lung cancer patients with
      bone metastases.
AB  - Bone metastases occur in 30-40% of patients with advanced non-small cell lung
      cancer (NSCLC). Several studies have demonstrated the direct anticancer effect of
      zoledronic acid against lung cancer; however, most of these studies are
      preclinical research. A total of 311 NSCLC patients with bone metastases who were
      treated with zoledronic acid at Zhejiang Cancer Hospital between 2008 and 2011
      were identified. Of these, 109 patients received zoledronic acid (4 mg
      intravenously every 21-28 days) more than 6 times (Group A), and the other 204
      patients received zoledronic acid <6 times (Group B). All patients received
      standard chemotherapy and other treatments. Survival time was significantly
      longer in Group A than in Group B (385 vs. 275 days; P = 0.002), and the
      incidence of malignant pleural effusion was lower in Group A than in Group B
      (22.0 vs. 33.8%; P = 0.041). In conclusion, our study results suggest that a
      longer zoledronic acid treatment period had a better effect on survival.
      Zoledronic acid use might decrease the incidence of malignant pleural effusion.

PMID- 24573640
TI  - Ubiquitin-specific protease 22: a novel molecular biomarker in glioma prognosis
      and therapeutics.
AB  - Ubiquitin-specific protease 22 (USP22) exhibits an important function in tumor
      progression and oncogenesis. The aim of this study was to investigate the role of
      USP22 and the association with its potential targets in patients with glioma. To
      our knowledge, this is the first study that determines the relationship between
      USP22 expression and clinicopathological significance in glioma. In our study,
      USP22 protein levels were detected by Western blot analysis. The protein levels
      of USP22 in glioma tissues were significantly higher than non-tumors. The
      immunohistochemistry results showed that USP22 protein was overexpressed in
      glioma tissues compared with non-tumors. The higher the grade of gliomas, the
      higher the level of USP22 expression. Further, the results of Kaplan-Meier
      analysis indicated that patients with high USP22 expression had significantly
      worse overall survival than patients with low expression of USP22. It suggested
      that USP22 overexpression may be associated with poor prognosis in patients with
      glioma. It may represent a novel prognostic biomarker or a target for improving
      the treatment efficiency of patients with glioma. 

PMID- 24573641
TI  - General assessment of copy number variation in normal and tumor tissues of the
      domestic dog (Canis lupus familiaris).
AB  - In recent years, characterization of a copy number variation (CNV) of the genomic
      DNA has provided evidence for the relationship of this type of genetic variation
      with the occurrence of a broad spectrum of diseases, including cancer lesions.
      Copy number variants (CNVs) also occur in the genomes of healthy individuals as a
      result of abnormal recombination processes in germ cells and have a hereditary
      character contributing to the natural genetic diversity. Recent image analysis
      methods and advanced computational techniques allow for identification of CNVs
      using SNPs genotyping microarrays based on the analysis of signal intensity
      observed for markers located in the specific genomic regions. In this study we
      used CanineHD BeadChip assay (Illumina) to identify both natural and cancer
      induced CNVs in the genomes of different dog breeds and in different cancer types
      occurring in this species. The obtained results showed that structural
      aberrations are a common phenomenon arising during a tumor progression and are
      more complex and widespread in tumors of mesenchymal tissue origin than in
      epithelial tissue originating tumors. The tumor derived CNVs, in comparison to
      healthy samples, were characterized by larger sizes of regions, higher number of
      amplifications, and in some cases encompassed genes with potential effect on
      tumor progression. 

PMID- 24573642
TI  - The effect of temperature on reproduction in the summer and winter annual
      Arabidopsis thaliana ecotypes Bur and Cvi.
AB  - BACKGROUND AND AIMS: Seed yield and dormancy status are key components of species
      fitness that are influenced by the maternal environment, in particular
      temperature. Responses to environmental conditions can differ between ecotypes of
      the same species. Therefore, to investigate the effect of maternal environment on
      seed production, this study compared two contrasting Arabidopsis thaliana
      ecotypes, Cape Verdi Isle (Cvi) and Burren (Bur). Cvi is adapted to a hot dry
      climate and Bur to a cool damp climate, and they exhibit winter and summer annual
      phenotypes, respectively. METHODS: Bur and Cvi plants were grown in reciprocal
      controlled environments that simulated their native environments. Reproductive
      development, seed production and subsequent germination behaviour were
      investigated. Measurements included: pollen viability, the development of floral
      structure, and germination at 10 and 25  degrees C in the light to determine
      dormancy status. Floral development was further investigated by applying
      gibberellins (GAs) to alter the pistil:stamen ratio. KEY RESULTS: Temperature
      during seed development determined seed dormancy status. In addition, seed yield
      was greatly reduced by higher temperature, especially in Bur (>90 %) compared
      with Cvi (approx. 50 %). The reproductive organs (i.e. stamens) of Bur plants
      were very sensitive to high temperature during early flowering. Viability of
      pollen was unaffected, but limited filament extension relative to that of the
      pistils resulted in failure to pollinate. Thus GA applied to flowers to enhance
      filament extension largely overcame the effect of high temperature on yield.
      CONCLUSIONS: High temperature in the maternal environment reduced dormancy and
      negatively affected the final seed yield of both ecotypes; however, the extent of
      these responses differed, demonstrating natural variation. Reduced seed yield in
      Bur resulted from altered floral development not reduced pollen viability. Future
      higher temperatures will impact on seed performance, but the consequences may
      differ significantly between ecotypes of the same species.

PMID- 24573643
TI  - Concentrations and resorption patterns of 13 nutrients in different plant
      functional types in the karst region of south-western China.
AB  - BACKGROUND AND AIMS: Elucidating the stoichiometry and resorption patterns of
      multiple nutrients is an essential requirement for a holistic understanding of
      plant nutrition and biogeochemical cycling. However, most studies have focused on
      nitrogen (N) and phosphorus (P), and largely ignored other nutrients. The current
      study aimed to determine relationships between resorption patterns and leaf
      nutrient status for 13 nutrient elements in a karst vegetation region. METHODS:
      Plant and soil samples were collected from four vegetation types in the karst
      region of south-western China and divided into eight plant functional types.
      Samples of newly expanded and recently senesced leaves were analysed to determine
      concentrations of boron (B), calcium (Ca), copper (Cu), iron (Fe), potassium (K),
      magnesium (Mg), manganese (Mn), molybdenum (Mo), N, sodium (Na), P, sulphur (S)
      and zinc (Zn). KEY RESULTS: Nutrient concentrations of the karst plants were
      lower than those normally found in other regions of China and the rest of the
      world, and plant growth was mainly limited by P. Overall, four nutrients revealed
      resorption [N (resorption efficiency 34.6 %), P (48.4 %), K (63.2 %) and Mg (13.2
      %)], seven nutrients [B (-16.1 %), Ca (-44.0 %), Cu (-14.5 %), Fe (-205.5 %), Mn
      (-72.5 %), Mo (-35.6 %) and Zn (-184.3 %)] showed accumulation in senesced leaves
      and two nutrients (Na and S) showed no resorption or accumulation. Resorption
      efficiencies of K and Mg and accumulation of B, Ca, Fe and Mn differed among
      plant functional types, and this strongly affected litter quality. Resorption
      efficiencies of N, P and K and accumulation of Ca and Zn increased with
      decreasing concentrations of these nutrients in green leaves. The N:P, N:K and
      N:Mg ratios in green leaves predicted resorption proficiency for N, K and Mg,
      respectively. CONCLUSIONS: The results emphasize the fact that nutrient
      resorption patterns strongly depend on element and plant functional type, which
      provides new insights into plant nutrient use strategies and nutrient cycling in
      karst ecosystems.

PMID- 24573644
TI  - Adaptation of an Acculturation Scale for African Refugee Women.
AB  - Newly-arrived African refugees are a vulnerable group of immigrants for whom no
      validated acculturation measures exist. A valid measurement tool is essential to
      understand how acculturative processes impact health and health disparities. We
      adapted the Bicultural Involvement Questionnaire (BIQ) to characterize its
      reliability among ethnic Somali women residing in Minnesota, and Somali, Somali
      Bantu, and Burundian women in Arizona. Surveys were administered to 164 adult
      women. Analyses were conducted along socio-demographic variables of ethnicity,
      geographic residence, age, and length of time in the United States through t
      tests and one-way analysis of variance. Exploratory factor analysis was conducted
      on the modified BIQ. Exploratory factor analyses yielded five subscales: "Speak
      Native Language", "Speak English Language", "Enjoy Native Activities", "Enjoy
      American Activities", and "Desired Ideal Culture". The subscales of the modified
      BIQ possessed Cronbach's alpha ranging from 0.68 to 0.92, suggestive that all
      subscales had acceptable to excellent internal consistency. The modified BIQ
      maintained its psychometric properties across geographic regions of resettled
      Central and East African refugees. 

PMID- 24573649
TI  - Paediatric thyroid surgery is safe--experiences at a tertiary surgical centre.
AB  - PRINCIPLES: Thyroidectomy in children is rare and mostly performed because of
      thyroid neoplasms. The aim of this study based on prospective data acquisition
      was to evaluate whether thyroid surgery in children can be performed as safely as
      in adults when undertaken by a team of adult endocrine surgeons and paediatric
      surgeons. METHODS: Between 2002 and 2012, 36 patients younger than 18 years
      underwent surgery for thyroid gland pathologies. All surgical procedures were
      performed by an experienced endocrine surgeon and a paediatric surgeon. Baseline
      demographic data, surgical procedure, duration of operation, length of hospital
      stay, and postoperative morbidity and mortality were analysed. RESULTS: The
      median age of all patients was 13 years (range 2-17 years), with predominantly
      female gender (n = 30, 83%). The majority of operations were performed because of
      benign thyroid disease (n = 27, 75%) and only a minority because of malignancy or
      genetic abnormality with predisposition for malignant transformation (MEN) (n =
      9, 25%). Total thyroidectomy was performed in the majority of the patients (n =
      24, 67%). The median duration of the surgical procedure was 153 minutes (range 90
      310 minutes). The median hospital stay was 5 days (3-1 days). One patient
      developed persistent hypoparathyroidism after neck dissection due to cancer. One
      persistent and two temporary recurrent nerve palsies occurred. CONCLUSION: This
      study demonstrated that paediatric thyroidectomy is safe as performed by this
      team of endocrine and paediatric surgeons, with acceptable morbidity even when
      total thyroidectomy was performed in the case of benign disease.

PMID- 24573652
TI  - Shikonin inhibits the growth of human prostate cancer cells via modulation of the
      androgen receptor.
AB  - Shikonin, a natural naphthoquinone isolated from the traditional Chinese medicine
      Zi Cao (gromwell), has been shown to possess tumor cell killing activity. The
      human androgen receptor (AR) is a nuclear transcription factor that serves as a
      major therapeutic target for prostate cancer. However, AR regulation by shikonin
      has not been reported. We investigated the effects of shikonin on the growth of
      prostate cancer cells. We observed that shikonin decreased the expression of AR
      at both the mRNA and the protein levels in LNCaP and 22RV1 human prostate cancer
      cells. The results from a luciferase assay showed that shikonin decreased the
      transcriptional activity of AR. Moreover, shikonin treatment inhibited AR target
      gene expression, PSA and growth inhibition of prostate cancer cells. In
      conclusion, the present study shows for the first time that shikonin treatment
      causes transcriptional repression of AR and inhibition of its nuclear
      localization in human prostate cancer cells. We propose that shikonin, an
      anticancer drug extracted from natural sources, induces inhibition of cell growth
      through modulation of AR in androgen-responsive prostate cancer cells and is a
      candidate for use in cancer chemotherapy for human prostate cancer.

PMID- 24573654
TI  - Inorganic-organic heteropolyacid-gold(I) hybrids: structures and catalytic
      applications.
AB  - Gold(I)-polyoxometalate hybrid complexes 1-4 ([PPh3AuMeCN]xH4-x SiW12O40, x=1-4)
      were synthesized and characterized. The structure of the primary gold(I)
      polyoxometalate 1 (x=1) was fully ascertained by XRD, FTIR, (31)P and (29)Si
      magic-angle spinning (MAS) NMR, mass spectroscopy, and SEM-energy dispersive X
      ray spectroscopy (EDX) techniques. Moreover, this complex exhibited better
      catalytic activity and selectivity compared with standard, homogeneous, gold
      catalysts in the new rearrangement of propargylic gem-diesters.

PMID- 24573653
TI  - Prophylactic bilateral salpingectomy (PBS) to reduce ovarian cancer risk
      incorporated in standard premenopausal hysterectomy: complications and re
      operation rate.
AB  - PURPOSE: Hysterectomy for benign conditions can be combined with bilateral
      salpingectomy to prevent re-intervention for malignant or benign fallopian tube
      pathologies. The objective of this study was to evaluate the benefit of
      prophylactic bilateral salpingectomy (PBS) in standard hysterectomy in
      premenopausal women. METHODS: This retrospective cohort study included all
      premenopausal patients at our institution who underwent laparoscopically assisted
      vaginal hysterectomy (LAVH) without oophorectomy for benign pathologies between
      2001 and 2007 [PBS group (LAVH + PBS), 2006-2007; non-PBS group (LAVH without
      PBS), 2001-2005]. Electronic and paper-based files as well as questionnaire
      responses were analyzed. In 2010, a survey on patients of a non-BRCA background
      with and without PBS was requested to complete a standardized questionnaire. Data
      were analyzed for differences between both subgroups regarding surgical outcome
      and adnexal pathologies as reported in the postoperative follow-up. RESULTS:
      Surgical outcomes of 540 patients (PBS: 127; non-PBS: 413) revealed no difference
      between groups. No preneoplastic or malignant lesions were diagnosed in the
      fallopian tubes. Follow-up (non-PBS 92 months, PBS 55 months; p < 0.01) responses
      from 295 (54.6 %) patients showed a higher incidence of benign adnexal
      pathologies in the non-PBS group (26.9 vs. 13.9 %; p = 0.02). The rate of LAVH
      related surgical re-intervention was higher in the non-PBS group (12.56 vs. 4.16
      %; p = 0.04). No malignant neoplasm was reported in the cohort. CONCLUSIONS: PBS
      did not increase the complication rate and reduced the incidence of adnexal
      pathologies requiring surgical re-intervention. Prospective trials should clarify
      the impact of PBS on cancer mortality.

PMID- 24573655
TI  - Effect of aging on magnetic resonance measures differentiating progressive
      supranuclear palsy from Parkinson's disease.
AB  - Imaging measurements, such as the ratio of the midsagittal areas of the midbrain
      and pons (midbrain/pons) and the Magnetic Resonance Parkinsonism Index (MRPI),
      have been proposed to differentiate progressive supranuclear palsy (PSP) from
      Parkinson's disease (PD). However, abnormal midbrain/pons values suggestive of
      PSP have also been reported in elderly individuals and in patients with PD. We
      investigated the effect of aging on single or combined imaging measurements of
      the brainstem. We calculated the midbrain/pons and the MRPI (the ratio of the
      midsagittal areas of the pons and the midbrain multiplied by the ratio of the
      middle cerebellar peduncle and superior cerebellar peduncle widths) in 152
      patients affected by PD, 25 patients with PSP, and a group of 81 age-matched and
      sex-matched healthy controls using a 3-Tesla magnetic resonance imaging scanner.
      In healthy controls, aging was negatively correlated with midsagittal area of the
      midbrain and midbrain/pons values. In patients with PD, in addition to the effect
      of aging, the disease status further influenced the midbrain/pons values (R(2)  =
      0.23; P < 0.001). In both groups, MRPI values were not influenced either by aging
      or by disease status. No effect of aging on either midbrain/pons or MRPI values
      was shown in the patients with PSP. Our findings indicated that the MRPI was not
      significantly influenced by aging or disease-related changes occurring in PD;
      whereas, in contrast, the midbrain/pons was influenced. Therefore, the MRPI
      appears to be a more reliable imaging measurement compared with midbrain/pons
      values for differentiating PSP from PD and controls in an elderly population.

PMID- 24573656
TI  - Exceptional expansion and conservation of a CT-repeat complex in the core
      promoter of PAXBP1 in primates.
AB  - Adaptive evolution may be linked with the genomic distribution and function of
      short tandem repeats (STRs). Proximity of the core promoter STRs to the +1
      transcription start site (TSS), and their mutable nature are characteristics that
      highlight those STRs as a novel source of interspecies variation. The PAXBP1 gene
      (alternatively known as GCFC1) core promoter contains the longest STR identified
      in a Homo sapiens gene core promoter. Indeed, this core promoter is a stretch of
      four consecutive CT-STRs. In the current study, we used the Ensembl, NCBI, and
      UCSC databases to analyze the evolutionary trend and functional implication of
      this CT-STR complex in six major lineages across vertebrates, including primates,
      non-primate mammals, birds, reptiles, amphibians, and fish. We observed
      exceptional expansion (>=4-repeats) and conservation of this CT-STR complex
      across primates, except prosimians, Microcebus murinus and Otolemur garnettii
      (Fisher exact P<4.1*10(-7)). H. sapiens has the most complex STR formula, and
      longest repeats. Macaca mulatta and Callithrix jacchus monkeys have the simplest
      STR formulas, and shortest repeat numbers. CT>=4-repeats were not detected in non
      primate lineages. Different length alleles across the PAXBP1 core promoter CT
      STRs significantly altered gene expression in vitro (P<0.001, t-test). PAXBP1 has
      a crucial role in craniofacial development, myogenesis, and spine morphogenesis,
      properties that have been diverged between primates and non-primates. To our
      knowledge, this is the first instance of expansion and conservation of a STR
      complex co-occurring specifically with the primate lineage.

PMID- 24573657
TI  - Combined SPECT/CT improves detection of initial bone invasion and determination
      of resection margins in squamous cell carcinoma of the head and neck compared to
      conventional imaging modalities.
AB  - PURPOSE: Knowledge of the presence and extent of bone infiltration is crucial for
      planning the resection of potential bone-infiltrating squamous cell carcinomas of
      the head and neck (HNSCC). Routinely, plain-film radiography, multislice computed
      tomography (MSCT) and magnetic resonance imaging (MRI) are used for preoperative
      staging, but they show relatively high rates of false-positive and false-negative
      findings. Scintigraphy with (99m)Tc-bisphosphonate has the ability to show
      increased metabolic bone activity. If combined with anatomical imaging (e.g.
      (SPECT)/CT), it facilitates the precise localization of malignant bone lesions.
      The aim of this study was to analyse the indications and advantages of SPECT/CT
      compared with standard imaging modalities and histology with regard to
      specificity and sensitivity METHODS: A longitudinally evaluated group of 30
      patients with biopsy-proven HNSCC adjacent to the mandible underwent (99m)Tc
      bisphosphonate SPECT/CT, MRI, MSCT and conventional radiography before partial or
      rim resection of the mandible was performed. Bone infiltration was first
      evaluated with plain films, MSCT and MRI. In a second reading, SPECT/CT data were
      taken into account. The results (region and certainty of bone invasion) were
      evaluated among the different imaging modalities and finally compared with
      histological specimens from surgical resection as the standard of reference. For
      a better evaluation of the hybrid property of SPECT/CT, a retrospectively
      evaluated group of 20 additional patients with tumour locations similar to those
      of the longitudinally examined SPECT/CT group underwent SPECT, MSCT and MRI. To
      assess the influence of dental foci on the specificity of the imaging modalities,
      all patients were separated into two subgroups depending on the presence or
      absence of teeth in the area of potential tumour-bone contact. RESULTS:
      Histologically proven bone infiltration was found in 17 patients (57 %) when
      analysed by conventional imaging modalities. SPECT/CT data revealed bone
      infiltration in two additional patients (7 %), who both showed discrete cortical
      bone erosion not visible by MSCT or MRI. There were no false-positive or false
      negative findings on SPECT/CT. The quality criteria for detecting bone
      involvement in HNSCC by SPECT/CT were as follows: sensitivity 100 % (lower 95 %
      confidence interval limit 80 %), specificity 100 % (75 %), positive predictive
      value 100 % (80 %) and negative predictive value 100 % (75 %). Corresponding data
      for MRI were 95 % (76 %), 94 % (73 %), 95 % (76 %) and 94 % (73 %), and for MSCT
      were 89 % (71 %), 100 % (85 %), 100 % (86 %) and 88 % (69 %). In the
      retrospective evaluation SPECT showed results similar to SPECT/CT. CONCLUSION:
      Hybrid SPECT/CT has a high specificity as it can provide additional information
      about the existence and local extent of malignant bone infiltration of the
      mandible. Although the sensitivity of conventional SPECT is similar to that of
      SPECT/CT, the latter provides a much better delineation of the local tumour-bone
      contact area. Based on this information, surgical intervention of the rim versus
      partial resection can be planned and performed more precisely. Patient outcome
      can be improved by avoiding undertreatment and unnecessary or overextended bone
      resections.

PMID- 24573658
TI  - Insight on AV-45 binding in white and grey matter from histogram analysis: a
      study on early Alzheimer's disease patients and healthy subjects.
AB  - PURPOSE: AV-45 amyloid biomarker is known to show uptake in white matter in
      patients with Alzheimer's disease (AD), but also in the healthy population. This
      binding, thought to be of a non-specific lipophilic nature, has not yet been
      investigated. The aim of this study was to determine the differential pattern of
      AV-45 binding in white matter in healthy and pathological populations. METHODS:
      We recruited 24 patients presenting with AD at an early stage and 17 matched,
      healthy subjects. We used an optimized positron emission tomography-magnetic
      resonance imaging (PET-MRI) registration method and an approach based on an
      intensity histogram using several indices. We compared the results of the
      intensity histogram analyses with a more canonical approach based on target-to
      cerebellum Standard Uptake Value (SUVr) in white and grey matter using MANOVA and
      discriminant analyses. A cluster analysis on white and grey matter histograms was
      also performed. RESULTS: White matter histogram analysis revealed significant
      differences between AD and healthy subjects, which were not revealed by SUVr
      analysis. However, white matter histograms were not decisive to discriminate
      groups, and indices based on grey matter only showed better discriminative power
      than SUVr. The cluster analysis divided our sample into two clusters, showing
      different uptakes in grey, but also in white matter. CONCLUSION: These results
      demonstrate that AV-45 binding in white matter conveys subtle information not
      detectable using the SUVr approach. Although it is not more efficient than
      standard SUVr in discriminating AD patients from healthy subjects, this
      information could reveal white matter modifications.

PMID- 24573659
TI  - The incidence of hiatal hernia after minimally invasive esophagectomy.
AB  - INTRODUCTION: Minimally invasive esophagectomy (MIE) has evolved as a means to
      minimize the morbidity of an operation which is traditionally associated with a
      significant risk. However, this approach may have its own unique postoperative
      complications. In this study, we describe the incidence and outcomes of hiatal
      hernia in a cohort of MIE patients. METHODS: Clinical follow-up data on 114
      patients who had undergone minimally invasive esophagectomy between 2003 and 2011
      were retrospectively reviewed. Clinical presentation and computed tomography (CT)
      scans of the chest and abdomen were used to establish the diagnosis of hiatal
      herniation after minimally invasive esophagectomy. Age, gender, presenting
      complaint, comorbid conditions, clinical tumor stage, surgical specimen size,
      length and cost of hospital admissions, operation performed for hiatal
      herniation, and mortality were all recorded for analysis. RESULTS: Nine (8%) of
      the 114 patients who underwent MIE had postoperative hiatal herniation. Five of
      these patients were asymptomatic. All patients except two who presented
      emergently were repaired laparoscopically on an elective basis. The average
      length of stay after hiatal hernia repair was 5.5 days (range 2-12) at an average
      charge of $40,785 (range $25,264-$83,953). At follow-up, one patient complained
      of symptoms associated with reflux. CONCLUSION: Hiatal herniation is not a rare
      event after MIE. It is also associated with significant health-care cost and may
      be lethal. Most occurrences appear to be asymptomatic and, if detected, can be
      repaired with good resolution of symptoms, minimal associated morbidity, and no
      mortality.

PMID- 24573660
TI  - Summaries for patients. Does the Mediterranean diet prevent diabetes?

PMID- 24573661
TI  - Prevention of diabetes with Mediterranean diets: a subgroup analysis of a
      randomized trial.
AB  - BACKGROUND: Interventions promoting weight loss can reduce the incidence of type
      2 diabetes mellitus. Whether dietary changes without calorie restriction also
      protect from diabetes has not been evaluated. OBJECTIVE: To assess the efficacy
      of Mediterranean diets for the primary prevention of diabetes in the Prevencion
      con Dieta Mediterranea trial, from October 2003 to December 2010 (median follow
      up, 4.1 years). DESIGN: Subgroup analysis of a multicenter, randomized trial.
      (Current Controlled Trials: ISRCTN35739639) SETTING: Primary care centers in
      Spain. PARTICIPANTS: Men and women without diabetes (3541 patients aged 55 to 80
      years) at high cardiovascular risk. INTERVENTION: Participants were randomly
      assigned and stratified by site, sex, and age but not diabetes status to receive
      1 of 3 diets: Mediterranean diet supplemented with extra-virgin olive oil (EVOO),
      Mediterranean diet supplemented with nuts, or a control diet (advice on a low-fat
      diet). No intervention to increase physical activity or lose weight was included.
      MEASUREMENTS: Incidence of new-onset type 2 diabetes mellitus (prespecified
      secondary outcome). RESULTS: During follow-up, 80, 92, and 101 new-onset cases of
      diabetes occurred in the Mediterranean diet supplemented with EVOO, Mediterranean
      diet supplemented with mixed nuts, and control diet groups, respectively,
      corresponding to rates of 16.0, 18.7, and 23.6 cases per 1000 person-years.
      Multivariate-adjusted hazard ratios were 0.60 (95% CI, 0.43 to 0.85) for the
      Mediterranean diet supplemented with EVOO and 0.82 (CI, 0.61 to 1.10) for the
      Mediterranean diet supplemented with nuts compared with the control diet.
      LIMITATIONS: Randomization was not stratified by diabetes status. Withdrawals
      were greater in the control group. CONCLUSION: A Mediterranean diet enriched with
      EVOO but without energy restrictions reduced diabetes risk among persons with
      high cardiovascular risk. PRIMARY FUNDING SOURCE: Instituto de Salud Carlos III.

PMID- 24573662
TI  - General internists' preferences and knowledge about the care of adult survivors
      of childhood cancer: a cross-sectional survey.
AB  - BACKGROUND: Adult childhood cancer survivors (CCSs) are at high risk for illness
      and premature death. Little is known about the physicians who provide their
      routine medical care. OBJECTIVE: To determine general internists' self-reported
      attitudes and knowledge about the care of CCSs. DESIGN: Cross-sectional survey.
      SETTING: Mailed survey delivered between September 2011 and August 2012.
      PARTICIPANTS: Random sample of 2000 U.S. general internists. MEASUREMENTS: Care
      preferences, comfort levels with caring for CCSs (7-point Likert scale: 1 = very
      uncomfortable, 7 = very comfortable), familiarity with available surveillance
      guidelines (7-point Likert scale: 1 = very unfamiliar, 7 = very familiar), and
      concordance with Children's Oncology Group Long-Term Follow-Up Guidelines in
      response to a clinical vignette. RESULTS: The response rate was 61.6% (1110 of
      1801). More than half the internists (51.1%) reported caring for at least 1 CCS;
      72.0% of these internists never received a treatment summary. On average,
      internists were "somewhat uncomfortable" caring for survivors of Hodgkin
      lymphoma, acute lymphoblastic leukemia, and osteosarcoma. Internists reported
      being "somewhat unfamiliar" with available surveillance guidelines. In response
      to a clinical vignette about a young adult survivor of Hodgkin lymphoma, 90.6% of
      respondents did not appropriately recommend yearly breast cancer surveillance,
      85.1% did not appropriately recommended cardiac surveillance, and 23.6% did not
      appropriately recommend yearly thyroid surveillance. Access to surveillance
      guidelines and treatment summaries were identified as the most useful resources
      for caring for CCSs. LIMITATION: Findings, based on self-report, may not reflect
      actual clinical practice. CONCLUSION: Although most general internists report
      involvement in the care of CCSs, many seem unfamiliar with available surveillance
      guidelines and would prefer to follow patients in collaboration with a cancer
      center. PRIMARY FUNDING SOURCE: National Cancer Institute.

PMID- 24573664
TI  - Health information technology: an updated systematic review with a focus on
      meaningful use.
AB  - BACKGROUND: Incentives offered by the U.S. government have spurred marked
      increases in use of health information technology (IT). PURPOSE: To update
      previous reviews and examine recent evidence that relates health IT
      functionalities prescribed in meaningful use regulations to key aspects of health
      care. DATA SOURCES: English-language articles in PubMed from January 2010 to
      August 2013. STUDY SELECTION: 236 studies, including pre-post and time-series
      designs and clinical trials that related the use of health IT to quality, safety,
      or efficiency. DATA EXTRACTION: Two independent reviewers extracted data on
      functionality, study outcomes, and context. DATA SYNTHESIS: Fifty-seven percent
      of the 236 studies evaluated clinical decision support and computerized provider
      order entry, whereas other meaningful use functionalities were rarely evaluated.
      Fifty-six percent of studies reported uniformly positive results, and an
      additional 21% reported mixed-positive effects. Reporting of context and
      implementation details was poor, and 61% of studies did not report any contextual
      details beyond basic information. LIMITATION: Potential for publication bias, and
      evaluated health IT systems and outcomes were heterogeneous and incompletely
      described. CONCLUSION: Strong evidence supports the use of clinical decision
      support and computerized provider order entry. However, insufficient reporting of
      implementation and context of use makes it impossible to determine why some
      health IT implementations are successful and others are not. The most important
      improvement that can be made in health IT evaluations is increased reporting of
      the effects of implementation and context. PRIMARY FUNDING SOURCE: Office of the
      National Coordinator.

PMID- 24573666
TI  - The adult childhood cancer survivor and the general internist: suggestions for
      patient and provider education.

PMID- 24573665
TI  - Fostering sustainable, integrated medical and behavioral health services in
      medical settings.
AB  - The integration of behavioral health (BH) and primary care services has been the
      subject of considerable attention for almost a decade. Such work has been
      motivated by the prevalence of chronic health problems in persons with BH
      conditions and correspondingly high rates of early death. Service integration
      efforts typically included cross-referral or bidirectional efforts to add some
      features of primary care to specialty BH settings or the reverse. This article
      proposes a third approach based on full service and financial integration and
      shows how it differs substantially from the other 2 models. This new model has
      the potential to bring much-needed BH services to persons served in primary care
      settings who have these conditions, while fostering integrated services in
      specialty settings for those with the most severe mental or substance use
      conditions. The Patient Protection and Affordable Care Act could provide a
      valuable opportunity to implement this third model. 

PMID- 24573663
TI  - Cost-effectiveness of treatment of diabetic macular edema.
AB  - BACKGROUND: Macular edema is the most common cause of vision loss among patients
      with diabetes. OBJECTIVE: To determine the cost-effectiveness of different
      treatments of diabetic macular edema (DME). DESIGN: Markov model. DATA SOURCES:
      Published literature and expert opinion. TARGET POPULATION: Patients with
      clinically significant DME. TIME HORIZON: Lifetime. PERSPECTIVE: Societal.
      INTERVENTION: Laser treatment, intraocular injections of triamcinolone or a
      vascular endothelial growth factor (VEGF) inhibitor, or a combination of both.
      OUTCOME MEASURES: Discounted costs, gains in quality-adjusted life-years (QALYs),
      and incremental cost-effectiveness ratios (ICERs). RESULTS OF BASE-CASE ANALYSIS:
      All treatments except laser monotherapy substantially reduced costs, and all
      treatments except triamcinolone monotherapy increased QALYs. Laser treatment plus
      a VEGF inhibitor achieved the greatest benefit, gaining 0.56 QALYs at a cost of
      $6975 for an ICER of $12 410 per QALY compared with laser treatment plus
      triamcinolone. Monotherapy with a VEGF inhibitor achieved similar outcomes to
      combination therapy with laser treatment plus a VEGF inhibitor. Laser monotherapy
      and triamcinolone monotherapy were less effective and more costly than
      combination therapy. RESULTS OF SENSITIVITY ANALYSIS: VEGF inhibitor monotherapy
      was sometimes preferred over laser treatment plus a VEGF inhibitor, depending on
      the reduction in quality of life with loss of visual acuity. When the VEGF
      inhibitor bevacizumab was as effective as ranibizumab, it was preferable because
      of its lower cost. LIMITATION: Long-term outcome data for treated and untreated
      diseases are limited. CONCLUSION: The most effective treatment of DME is VEGF
      inhibitor injections with or without laser treatment. This therapy compares
      favorably with cost-effective interventions for other conditions. PRIMARY FUNDING
      SOURCE: Agency for Healthcare Research and Quality.

PMID- 24573667
TI  - Podcast pearls in residency training.

PMID- 24573668
TI  - Acute pancreatitis after high-intensity focused ultrasonography for body
      sculpting.

PMID- 24573669
TI  - In the clinic. Stable ischemic heart disease.

PMID- 24573670
TI  - KIAA1199 and its biological role in human cancer and cancer cells (review).
AB  - KIAA1199 is a gene included in the Human Unidentified Gene-Encoded (HUGE) large
      protein database which contains more than 2,400 members identified in the Kazusa
      cDNA sequencing project. Early studies described KIAA1199 as an inner ear
      specific protein in which 3 point mutations were found to be associated with non
      syndromic hearing loss. Recently, KIAA1199 has been found to play a central role
      in hyaluronan binding and depolymerisation, and a small number of studies
      indicate its senescence/apoptosis-promoting role. An increasing body of evidence
      suggests its involvement in cancer progression, metastasis and poor prognosis of
      patients with cancer as determined in clinical studies. It has also been shown,
      in vitro, that KIAA1199 influences the proliferation, adhesion, motility,
      invasiveness and epithelial-to-mesenchymal transition of cancer cells. Pathway
      signalling analysis found that KIAA1199 is a likely target gene of the Wnt/beta
      catenin signalling pathway. Therefore, KIAA1199 may be a new and prospective
      target for cancer therapy, although further in vitro and in vivo investigations
      are required.

PMID- 24573671
TI  - Mechanism of immunotoxicological effects of tributyltin chloride on murine
      thymocytes.
AB  - Tributyltin-chloride, a well-known organotin compound, is a widespread
      environmental toxicant. The immunotoxic effects of tributyltin-chloride on
      mammalian system and its mechanism is still unclear. This study is designed to
      explore the mode of action of tributyltin-induced apoptosis and other parallel
      apoptotic pathways in murine thymocytes. The earliest response in oxidative
      stress followed by mitochondrial membrane depolarization and caspase-3 activation
      has been observed. Pre-treatment with N-acetyl cysteine and buthionine
      sulfoximine effectively inhibited the tributyltin-induced apoptotic DNA and
      elevated the sub G1 population, respectively. Caspase inhibitors pretreatment
      prevent tributyltin-induced apoptosis. Western blot and flow cytometry indicate
      no translocation of apoptosis-inducing factor and endonuclease G in the nuclear
      fraction from mitochondria. Intracellular Ca(2+) levels are significantly raised
      by tributyltin chloride. These results clearly demonstrate caspase-dependent
      apoptotic pathway and support the role of oxidative stress, mitochondrial
      membrane depolarization, caspase-3 activation, and calcium during tributyltin
      chloride (TBTC)-induced thymic apoptosis. 

PMID- 24573672
TI  - MicroRNA-137 is a novel hypoxia-responsive microRNA that inhibits mitophagy via
      regulation of two mitophagy receptors FUNDC1 and NIX.
AB  - Mitophagy receptors mediate the selective recognition and targeting of damaged
      mitochondria by autophagosomes. The mechanism for the regulation of these
      receptors remains unknown. Here, we demonstrated that a novel hypoxia-responsive
      microRNA, microRNA-137 (miR-137), markedly inhibits mitochondrial degradation by
      autophagy without affecting global autophagy. miR-137 targets the expression of
      two mitophagy receptors NIX and FUNDC1. Impaired mitophagy in response to hypoxia
      caused by miR-137 is reversed by re-expression of FUNDC1 and NIX expression
      vectors lacking the miR-137 recognition sites at their 3' UTR. Conversely, miR
      137 also suppresses the mitophagy induced by fundc1 (CDS+3'UTR) but not fundc1
      (CDS) overexpression. Finally, we found that miR-137 inhibits mitophagy by
      reducing the expression of the mitophagy receptor thereby leads to inadequate
      interaction between mitophagy receptor and LC3. Our results demonstrated the
      regulatory role of miRNA to mitophagy receptors and revealed a novel link between
      miR-137 and mitophagy. 

PMID- 24573673
TI  - A histidine aspartate ionic lock gates the iron passage in miniferritins from
      Mycobacterium smegmatis.
AB  - Dps (DNA-binding protein from starved cells) are dodecameric assemblies belonging
      to the ferritin family that can bind DNA, carry out ferroxidation, and store iron
      in their shells. The ferritin-like trimeric pore harbors the channel for the
      entry and exit of iron. By representing the structure of Dps as a network we have
      identified a charge-driven interface formed by a histidine aspartate cluster at
      the pore interface unique to Mycobacterium smegmatis Dps protein, MsDps2. Site
      directed mutagenesis was employed to generate mutants to disrupt the charged
      interactions. Kinetics of iron uptake/release of the wild type and mutants were
      compared. Crystal structures were solved at a resolution of 1.8-2.2 A for the
      various mutants to compare structural alterations vis a vis the wild type
      protein. The substitutions at the pore interface resulted in alterations in the
      side chain conformations leading to an overall weakening of the interface
      network, especially in cases of substitutions that alter the charge at the pore
      interface. Contrary to earlier findings where conserved aspartate residues were
      found crucial for iron release, we propose here that in the case of MsDps2, it is
      the interplay of negative-positive potentials at the pore that enables proper
      functioning of the protein. In similar studies in ferritins, negative and
      positive patches near the iron exit pore were found to be important in iron
      uptake/release kinetics. The unique ionic cluster in MsDps2 makes it a suitable
      candidate to act as nano-delivery vehicle, as these gated pores can be
      manipulated to exhibit conformations allowing for slow or fast rates of iron
      release. 

PMID- 24573674
TI  - Monoacylglycerol acyltransferase-2 is a tetrameric enzyme that selectively
      heterodimerizes with diacylglycerol acyltransferase-1.
AB  - Acyl-CoA:monoacylglycerol acyltransferases (MGATs) and diacylglycerol
      acyltransferases (DGATs) catalyze the two consecutive steps in the synthesis of
      triacylglycerol, a key process required for dietary fat absorption into the
      enterocytes of the small intestine. In this report, we investigated the tendency
      of MGAT2 to form an enzyme complex with DGAT1 and DGAT2 in intact cells. We
      demonstrated that in addition to the 38-kDa monomer of the MGAT2 enzyme predicted
      by its peptide sequence, a 76-kDa moiety was detected in SDS-PAGE without
      reducing agent and heat inactivation. The 76-kDa MGAT2 moiety was greatly
      enhanced by treatment with a cross-linking reagent in intact cells. Additionally,
      the cross-linking reagent dose-dependently yielded a band corresponding to the
      tetramer (152 kDa) in SDS-PAGE, suggesting that the MGAT2 enzyme primarily
      functions as a homotetrameric protein and as a tetrameric protein. Likewise,
      DGAT1 also forms a homodimer under nondenaturing conditions. When co-expressed in
      COS-7 cells, MGAT2 heterodimerized with DGAT1 without treatment with a cross
      linking reagent. MGAT2 also co-eluted with DGAT1 on a gel filtration column,
      suggesting that the two enzymes form a complex in intact cells. In contrast,
      MGAT2 did not heterodimerize with DGAT2 when co-expressed in COS-7 cells, despite
      high sequence homology between the two enzymes. Furthermore, systematic deletion
      analysis demonstrates that N-terminal amino acids 35-80 of DGAT1, but not a
      signal peptide at the N terminus of MGAT2, is required for the
      heterodimerization. Finally, co-expression of MGAT2 with DGAT1 significantly
      increased lipogenesis in COS-7 cells, indicating the functional importance of the
      dimerization. 

PMID- 24573675
TI  - The Ddc1-Mec3-Rad17 sliding clamp regulates histone-histone chaperone
      interactions and DNA replication-coupled nucleosome assembly in budding yeast.
AB  - The maintenance of genome integrity is regulated in part by chromatin structure
      and factors involved in the DNA damage response pathway. Nucleosome assembly is a
      highly regulated process that restores chromatin structure after DNA replication,
      DNA repair, and gene transcription. During S phase the histone chaperones Asf1,
      CAF-1, and Rtt106 coordinate to deposit newly synthesized histones H3-H4 onto
      replicated DNA in budding yeast. Here we describe synthetic genetic interactions
      between RTT106 and the DDC1-MEC3-RAD17 (9-1-1) complex, a sliding clamp
      functioning in the S phase DNA damage and replication checkpoint response, upon
      treatment with DNA damaging agents. The DNA damage sensitivity of rad17Delta
      rtt106Delta cells depends on the function of Rtt106 in nucleosome assembly.
      Epistasis analysis reveals that 9-1-1 complex components interact with multiple
      DNA replication-coupled nucleosome assembly factors, including Rtt106, CAF-1, and
      lysine residues of H3-H4. Furthermore, rad17Delta cells exhibit defects in the
      deposition of newly synthesized H3-H4 onto replicated DNA. Finally, deletion of
      RAD17 results in increased association of Asf1 with checkpoint kinase Rad53,
      which may lead to the observed reduction in Asf1-H3 interaction in rad17Delta
      mutant cells. In addition, we observed that the interaction between histone H3-H4
      with histone chaperone CAF-1 or Rtt106 increases in cells lacking Rad17. These
      results support the idea that the 9-1-1 checkpoint protein regulates DNA
      replication-coupled nucleosome assembly in part through regulating histone
      histone chaperone interactions. 

PMID- 24573676
TI  - Tipin functions in the protection against topoisomerase I inhibitor.
AB  - The replication fork temporarily stalls when encountering an obstacle on the DNA,
      and replication resumes after the barrier is removed. Simultaneously, activation
      of the replication checkpoint delays the progression of S phase and inhibits late
      origin firing. Camptothecin (CPT), a topoisomerase I (Top1) inhibitor, acts as a
      DNA replication barrier by inducing the covalent retention of Top1 on DNA. The
      Timeless-Tipin complex, a component of the replication fork machinery, plays a
      role in replication checkpoint activation and stabilization of the replication
      fork. However, the role of the Timeless-Tipin complex in overcoming the CPT
      induced replication block remains elusive. Here, we generated viable TIPIN gene
      knock-out (KO) DT40 cells showing delayed S phase progression and increased cell
      death. TIPIN KO cells were hypersensitive to CPT. However, homologous
      recombination and replication checkpoint were activated normally, whereas DNA
      synthesis activity was markedly decreased in CPT-treated TIPIN KO cells.
      Proteasome-dependent degradation of chromatin-bound Top1 was induced in TIPIN KO
      cells upon CPT treatment, and pretreatment with aphidicolin, a DNA polymerase
      inhibitor, suppressed both CPT sensitivity and Top1 degradation. Taken together,
      our data indicate that replication forks formed without Tipin may collide at a
      high rate with Top1 retained on DNA by CPT treatment, leading to CPT
      hypersensitivity and Top1 degradation in TIPIN KO cells. 

PMID- 24573677
TI  - The DDN catalytic motif is required for Metnase functions in non-homologous end
      joining (NHEJ) repair and replication restart.
AB  - Metnase (or SETMAR) arose from a chimeric fusion of the Hsmar1 transposase
      downstream of a protein methylase in anthropoid primates. Although the Metnase
      transposase domain has been largely conserved, its catalytic motif (DDN) differs
      from the DDD motif of related transposases, which may be important for its role
      as a DNA repair factor and its enzymatic activities. Here, we show that
      substitution of DDN(610) with either DDD(610) or DDE(610) significantly reduced
      in vivo functions of Metnase in NHEJ repair and accelerated restart of
      replication forks. We next tested whether the DDD or DDE mutants cleave single
      strand extensions and flaps in partial duplex DNA and pseudo-Tyr structures that
      mimic stalled replication forks. Neither substrate is cleaved by the DDD or DDE
      mutant, under the conditions where wild-type Metnase effectively cleaves ssDNA
      overhangs. We then characterized the ssDNA-binding activity of the Metnase
      transposase domain and found that the catalytic domain binds ssDNA but not dsDNA,
      whereas dsDNA binding activity resides in the helix-turn-helix DNA binding
      domain. Substitution of Asn-610 with either Asp or Glu within the transposase
      domain significantly reduces ssDNA binding activity. Collectively, our results
      suggest that a single mutation DDN(610) -> DDD(610), which restores the ancestral
      catalytic site, results in loss of function in Metnase. 

PMID- 24573678
TI  - Insight into the roles of helicase motif Ia by characterizing Fanconi anemia
      group J protein (FANCJ) patient mutations.
AB  - Helicases are molecular motors that couple the energy of ATP hydrolysis to the
      unwinding and remodeling of structured DNA or RNA, which is coordinated by
      conserved helicase motifs. FANCJ is a DNA helicase that is genetically linked to
      Fanconi anemia, breast cancer, and ovarian cancer. Here, we characterized two
      Fanconi anemia patient mutations, R251C and Q255H, that are localized in helicase
      motif Ia. Our genetic complementation analysis revealed that both the R251C and
      Q255H alleles failed to rescue cisplatin sensitivity of a FANCJ null cell line as
      detected by cell survival or gamma-H2AX foci formation. Furthermore, our
      biochemical assays demonstrated that both purified recombinant proteins abolished
      DNA helicase activity and failed to disrupt the DNA-protein complex.
      Intriguingly, R251C impaired DNA binding ability to single-strand DNA and double
      strand DNA, whereas Q255H retained higher binding activity to these DNA
      substrates compared with wild-type FANCJ protein. Consequently, R251C abolished
      its DNA-dependent ATP hydrolysis activity, whereas Q255H retained normal ATPase
      activity. Physically, R251C had reduced ATP binding ability, whereas Q255H had
      normal ATP binding ability and could translocate on single-strand DNA. Although
      both proteins were recruited to damage sites in our laser-activated confocal
      assays, they lost their DNA repair function, which explains why they exerted a
      domain negative effect when expressed in a wild-type background. Taken together,
      our work not only reveals the structural function of helicase motif Ia but also
      provides the molecular pathology of FANCJ in related diseases. 

PMID- 24573679
TI  - Signaling by the extracellular matrix protein Reelin promotes granulosa cell
      proliferation in the chicken follicle.
AB  - Chicken oocytes develop in follicles and reach an enormous size because of a
      massive uptake of yolk precursors such as very low density lipoprotein and
      vitellogenin. Oocyte growth is supported by theca cells and granulosa cells,
      which establish dynamic and highly organized cell layers surrounding the oocyte.
      The signaling processes orchestrating the development of these layered structures
      are largely unknown. Here we demonstrate that the Reelin pathway, which
      determines the development of layered neuronal structures in the brain, is also
      active in chicken follicles. Reelin, which is expressed in theca cells, triggers
      a signal in granulosa cells via apolipoprotein E receptor 2 and the very low
      density lipoprotein receptor, resulting in the phosphorylation of disabled-1 and
      consecutive activation of the phosphatidylinositol 3-kinase/Akt pathway. This
      signaling pathway supports the proliferation of differentiated granulosa cells to
      keep up with the demand of cells to cover the rapidly increasing surface of the
      giant germ cell. 

PMID- 24573680
TI  - Defective chemokine signal integration in leukocytes lacking activator of G
      protein signaling 3 (AGS3).
AB  - Activator of G-protein signaling 3 (AGS3, gene name G-protein signaling modulator
      1, Gpsm1), an accessory protein for G-protein signaling, has functional roles in
      the kidney and CNS. Here we show that AGS3 is expressed in spleen, thymus, and
      bone marrow-derived dendritic cells, and is up-regulated upon leukocyte
      activation. We explored the role of AGS3 in immune cell function by
      characterizing chemokine receptor signaling in leukocytes from mice lacking AGS3.
      No obvious differences in lymphocyte subsets were observed. Interestingly,
      however, AGS3-null B and T lymphocytes and bone marrow-derived dendritic cells
      exhibited significant chemotactic defects as well as reductions in chemokine
      stimulated calcium mobilization and altered ERK and Akt activation. These studies
      indicate a role for AGS3 in the regulation of G-protein signaling in the immune
      system, providing unexpected venues for the potential development of therapeutic
      agents that modulate immune function by targeting these regulatory mechanisms. 

PMID- 24573682
TI  - Mechanistic investigations of unsaturated glucuronyl hydrolase from Clostridium
      perfringens.
AB  - Experiments were carried out to probe the details of the hydration-initiated
      hydrolysis catalyzed by the Clostridium perfringens unsaturated glucuronyl
      hydrolase of glycoside hydrolase family 88 in the CAZy classification system.
      Direct (1)H NMR monitoring of the enzymatic reaction detected no accumulated
      reaction intermediates in solution, suggesting that rearrangement of the initial
      hydration product occurs on-enzyme. An attempt at mechanism-based trapping of on
      enzyme intermediates using a 1,1-difluoro-substrate was unsuccessful because the
      probe was too deactivated to be turned over by the enzyme. Kinetic isotope
      effects arising from deuterium-for-hydrogen substitution at carbons 1 and 4
      provide evidence for separate first-irreversible and overall rate-determining
      steps in the hydration reaction, with two potential mechanisms proposed to
      explain these results. Based on the positioning of catalytic residues in the
      enzyme active site, the lack of efficient turnover of a 2-deoxy-2-fluoro
      substrate, and several unsuccessful attempts at confirmation of a simpler
      mechanism involving a covalent glycosyl-enzyme intermediate, the most plausible
      mechanism is one involving an intermediate bearing an epoxide on carbons 1 and 2.

PMID- 24573681
TI  - Bacillus cereus Certhrax ADP-ribosylates vinculin to disrupt focal adhesion
      complexes and cell adhesion.
AB  - Bacillus cereus is often associated with mild to moderate gastroenteritis;
      however, some recent isolates cause inhalational anthrax-like diseases and death.
      These potential emerging human pathogens express multiple virulence factors. B.
      cereus strain G9241 expresses anthrax toxin, several polysaccharide capsules, and
      the novel ADP-ribosyltransferase, Certhrax. In this study, we show that Certhrax
      ADP-ribosylates Arg-433 of vinculin, a protein that coordinates actin
      cytoskeleton and extracellular matrix interactions. ADP-ribosylation of vinculin
      disrupted focal adhesion complexes and redistributed vinculin to the cytoplasm.
      Exogenous vinculin rescued these phenotypes. This provides a mechanism for strain
      G9241 to breach host barrier defenses and promote bacterial growth and spread.
      Certhrax is the first bacterial toxin to add a post-translational modification to
      vinculin to disrupt the actin cytoskeleton. 

PMID- 24573683
TI  - Antibodies that detect O-linked beta-D-N-acetylglucosamine on the extracellular
      domain of cell surface glycoproteins.
AB  - The transfer of N-acetylglucosamine (GlcNAc) to Ser or Thr in cytoplasmic and
      nuclear proteins is a well known post-translational modification that is
      catalyzed by the O-GlcNAc transferase OGT. A more recently identified O-GlcNAc
      transferase, EOGT, functions in the secretory pathway and transfers O-GlcNAc to
      proteins with epidermal growth factor-like (EGF) repeats. A number of antibodies
      that detect O-GlcNAc in cytosolic and nuclear extracts have been described
      previously. Here we compare seven of these antibodies (CTD110.6, 10D8, RL2,
      HGAC85, 18B10.C7(#3), 9D1.E4(#10), and 1F5.D6 (#14) for detection of the O-GlcNAc
      modification on extracellular domains of membrane or secreted glycoproteins that
      may also carry various N- and O-glycans. We found that CTD110.6 binds not only to
      O-GlcNAc on proteins but also to terminal beta-GlcNAc on the complex N-glycans of
      Lec8 Chinese hamster ovary (CHO) cells that lack UDP-Gal transporter activity and
      express GlcNAc-terminating, complex N-glycans. We show that CTD110.6, #3, and #10
      antibodies can be used to detect cell surface glycoproteins bearing O-GlcNAc.
      Cell surface glycoproteins recognized by CTD110.6 antibody included NOTCH1 that
      possesses many EGF repeats with a consensus site for EOGT. Knockdown of CHO Eogt
      reduced binding of CTD110.6 to Lec1 CHO cells, and expression of a human EOGT
      cDNA increased the O-GlcNAc signal on Lec1 cells and the extracellular domain of
      NOTCH1. Thus, with careful controls, antibodies CTD110.6 (IgM), #3 (IgG), and #10
      (IgG) can be used to detect membrane and secreted proteins modified by O-GlcNAc
      on EGF repeats. 

PMID- 24573686
TI  - beta-Hydroxy-gamma-lactones as nucleophiles in the Nicholas reaction for the
      synthesis of oxepene rings. Enantioselective formal synthesis of (-)
      isolaurepinnacin and (+)-rogioloxepane A.
AB  - The enantioselective formal synthesis of (-)-isolaurepinnacin and (+)
      rogioloxepane A has been achieved. The key steps are an intermolecular Nicholas
      reaction with a beta-hydroxy-gamma-lactone as the nucleophile, to form branched
      linear ethers, and an olefin ring-closing metathesis to obtain the oxepene core. 

PMID- 24573684
TI  - The presence of multiple cellular defects associated with a novel G50E iron
      sulfur cluster scaffold protein (ISCU) mutation leads to development of
      mitochondrial myopathy.
AB  - Iron-sulfur (Fe-S) clusters are versatile cofactors involved in regulating
      multiple physiological activities, including energy generation through cellular
      respiration. Initially, the Fe-S clusters are assembled on a conserved scaffold
      protein, iron-sulfur cluster scaffold protein (ISCU), in coordination with iron
      and sulfur donor proteins in human mitochondria. Loss of ISCU function leads to
      myopathy, characterized by muscle wasting and cardiac hypertrophy. In addition to
      the homozygous ISCU mutation (g.7044G->C), compound heterozygous patients with
      severe myopathy have been identified to carry the c.149G->A missense mutation
      converting the glycine 50 residue to glutamate. However, the physiological
      defects and molecular mechanism associated with G50E mutation have not been
      elucidated. In this report, we uncover mechanistic insights concerning how the
      G50E ISCU mutation in humans leads to the development of severe ISCU myopathy,
      using a human cell line and yeast as the model systems. The biochemical results
      highlight that the G50E mutation results in compromised interaction with the
      sulfur donor NFS1 and the J-protein HSCB, thus impairing the rate of Fe-S cluster
      synthesis. As a result, electron transport chain complexes show significant
      reduction in their redox properties, leading to loss of cellular respiration.
      Furthermore, the G50E mutant mitochondria display enhancement in iron level and
      reactive oxygen species, thereby causing oxidative stress leading to impairment
      in the mitochondrial functions. Thus, our findings provide compelling evidence
      that the respiration defect due to impaired biogenesis of Fe-S clusters in
      myopathy patients leads to manifestation of complex clinical symptoms. 

PMID- 24573685
TI  - Sensor domain of histidine kinase KinB of Pseudomonas: a helix-swapped dimer.
AB  - The overproduction of polysaccharide alginate is responsible for the formation of
      mucus in the lungs of cystic fibrosis patients. Histidine kinase KinB of the KinB
      AlgB two-component system in Pseudomonas aeruginosa acts as a negative regulator
      of alginate biosynthesis. The modular architecture of KinB is similar to other
      histidine kinases. However, its periplasmic signal sensor domain is unique and is
      found only in the Pseudomonas genus. Here, we present the first crystal
      structures of the KinB sensor domain. The domain is a dimer in solution, and in
      the crystal it shows an atypical dimer of a helix-swapped four-helix bundle. A
      positively charged cavity is formed on the dimer interface and involves several
      strictly conserved residues, including Arg-60. A phosphate anion is bound
      asymmetrically in one of the structures. In silico docking identified several
      monophosphorylated sugars, including beta-D-fructose 6-phosphate and beta-D
      mannose 6-phosphate, a precursor and an intermediate of alginate synthesis,
      respectively, as potential KinB ligands. Ligand binding was confirmed
      experimentally. Conformational transition from a symmetric to an asymmetric
      structure and decreasing dimer stability caused by ligand binding may be a part
      of the signal transduction mechanism of the KinB-AlgB two-component system.

PMID- 24573688
TI  - Training children in pedestrian safety: distinguishing gains in knowledge from
      gains in safe behavior.
AB  - Pedestrian injuries contribute greatly to child morbidity and mortality. Recent
      evidence suggests that training within virtual pedestrian environments may
      improve children's street crossing skills, but may not convey knowledge about
      safety in street environments. We hypothesized that (a) children will gain
      pedestrian safety knowledge via videos/software/internet websites, but not when
      trained by virtual pedestrian environment or other strategies; (b) pedestrian
      safety knowledge will be associated with safe pedestrian behavior both before and
      after training; and (c) increases in knowledge will be associated with increases
      in safe behavior among children trained individually at streetside locations, but
      not those trained by means of other strategies. We analyzed data from a
      randomized controlled trial evaluating pedestrian safety training. We randomly
      assigned 240 children ages 7-8 to one of four training conditions:
      videos/software/internet, virtual reality (VR), individualized streetside
      instruction, or a no-contact control. Both virtual and field simulations of
      street crossing at 2-lane bi-directional mid-block locations assessed pedestrian
      behavior at baseline, post-training, and 6-month follow-up. Pedestrian knowledge
      was assessed orally on all three occasions. Children trained by
      videos/software/internet, and those trained individually, showed increased
      knowledge following training relative to children in the other groups (ps <
      0.01). Correlations between pedestrian safety knowledge and pedestrian behavior
      were mostly non-significant. Correlations between change in knowledge and change
      in behavior from pre- to post-intervention also were non-significant, both for
      the full sample and within conditions. Children trained using
      videos/software/internet gained knowledge but did not change their behavior.
      Children trained individually gained in both knowledge and safer behavior.
      Children trained virtually gained in safer behavior but not knowledge. If VR is
      used for training, tools like videos/internet might effectively supplement
      training. We discovered few associations between knowledge and behavior, and none
      between changes in knowledge and behavior. Pedestrian safety knowledge and safe
      pedestrian behavior may be orthogonal constructs that should be considered
      independently for research and training purposes. 

PMID- 24573690
TI  - Hypoxia promotes stem-like properties of laryngeal cancer cell lines by
      increasing the CD133+ stem cell fraction.
AB  - Evidence indicates that a hypoxic micro-environment plays an essential role in
      the regulation of cancer stem cells (CSCs). However, whether hypoxia is able to
      regulate the stem-like biological properties of laryngeal cancer cells remains
      unknown. In this study, we investigated the influence of hypoxia on the stemness
      of two laryngeal cancer cell lines, Hep-2 and AMC-HN-8. We cultured the two cell
      lines under hypoxia and normoxia and examined the influence of hypoxia on the
      expression of hypoxia-inducible factors (HIFs) and the cancer stem-like
      properties of these cells, including cell cycle distribution, expression of stem
      cell genes (OCT4, SOX2 and NANOG) and laryngeal CSC surface marker (CD133),
      proliferation, invasion, colony formation and sphere formation capacity. We
      determined that both of these cell lines, when maintained under hypoxic
      conditions, showed expanded cells in the G0/G1 phase, exhibited preferential
      expression of stem cell genes and CD133, and manifested upregulation of HIFs.
      When treated with hypoxia followed by normoxia exposure, the two cell lines
      exhibited enhanced capacities for proliferation, invasion, and sphere and colony
      formation compared with cells maintained consistently under normoxia. Our
      findings indicate that a hypoxic microenvironment may upgrade the stem-like
      biological properties of laryngeal cancer cell lines by the expansion of the
      CD133(+) stem cell fraction.

PMID- 24573687
TI  - Prognostic and predictive value of copy number alterations in invasive breast
      cancer as determined by multiplex ligation-dependent probe amplification.
AB  - BACKGROUND: Breast cancer is a leading cause of morbidity and mortality in women
      worldwide. About 70 % of breast cancers are estrogen receptor (ER) positive.
      Blocking estrogen action by tamoxifen has been the treatment of choice in ER
      positive breast cancers for more than 30 years. In the past, several studies have
      revealed associations between gene copy number alterations and responsiveness to
      tamoxifen therapy, but so far no single gene copy number alteration could
      completely explain the response variation observed between individual breast
      cancer patients. Here, we set out to perform a simultaneous analysis of copy
      number alterations of several genes involved in the prognosis and response to
      therapy by multiplex ligation-dependent probe amplification (MLPA). METHODS: A
      case-control study was designed encompassing 170 non-metastatic ER positive
      breast cancer patients (case group = 85, control group = 85). All patients in the
      control group had received standard adjuvant tamoxifen treatment for 5 years
      without any evidence of recurrence. Patients in the case group had experienced
      early recurrences while receiving tamoxifen treatment. 76 % of the patients of
      the case group and 73 % of the patients of the control group had received
      anthracycline-based adjuvant chemotherapy. Gene copy number alterations detected
      by MLPA in both groups were compared. RESULTS: Amplification of CCND1 (OR = 3.13;
      95 % CI = 1.35 to 7.26; p = 0.006) and TOP2A (OR = 3.05; 95 % CI = 1.13 to 8.24;
      p = 0.022) were significantly more prevalent in the case group, compared to the
      control group. In a multivariate analysis CCND1 (p = 0.01) and TOP2A (p = 0.041)
      amplifications remained significant predictors of recurrence. CONCLUSIONS: Our
      results indicate that CCND1 amplification may serve as a useful biomarker for
      hormone responsiveness, and that TOP2A amplification may serve as a useful
      prognostic biomarker.

PMID- 24573692
TI  - Mode of action of S-methyl-N, N-diethylthiocarbamate sulfoxide (DETC-MeSO) as a
      novel therapy for stroke in a rat model.
AB  - One approach for protecting neurons from excitotoxic damage in stroke is to
      attenuate receptor activity with specific antagonists. S-Methyl-N, N
      diethylthiocarbamate sulfoxide (DETC-MeSO), the active metabolite of disulfiram,
      has been shown to be a partial antagonist of glutamate receptors and effective in
      reducing seizure. First, we investigated neuroprotective effect of DETC-MeSO on
      primary cortical neuronal culture under hypoxia/reoxygenation condition in vitro.
      Then, DETC-MeSO was administered subcutaneously for 4 and 8 days with the first
      injection occurring 1 h before or 24 h after reperfusion in the rat middle
      cerebral artery occlusion stroke model. Rats were subjected to the neuroscore
      test, and the brain was analyzed for infarct size. Monitoring neurotransmitter
      release was carried out by microdialysis. Heat shock proteins, key proteins
      involved in apoptosis and endoplasmic reticulum (ER) stress, were analyzed by
      immunoblotting. DETC-MeSO greatly reduced both cell death following
      hypoxia/reoxygenation and brain infarct size. It improved performance on the
      neuroscore test and attenuated proteolysis of alphaII-spectrin. The level of pro
      apoptotic proteins declined, and anti-apoptotic and HSP27 protein expressions
      were markedly increased. Levels of the ER stress protein markers p-PERK, p
      eIF2alpha, ATF4, JNK, XBP-1, GADD34, and CHOP significantly declined after DETC
      MeSO administration. Microdialysis data showed that DETC-MeSO increased high
      potassium-induced striatal dopamine release indicating that more neurons were
      protected and survived under ischemic insult in the presence of DETC-MeSO. We
      also showed that DETC-MeSO can prevent gliosis. DETC-MeSO elicits neuroprotection
      through the preservation of ER resulting in reduction of apoptosis by increase of
      anti-apoptotic proteins and decrease of pro-apoptotic proteins.

PMID- 24573694
TI  - In vivo genome-wide binding of Id2 to E2F4 target genes as part of a reversible
      program in mice liver.
AB  - The inhibitor of differentiation Id2, a protein lacking the basic DNA-binding
      domain, is involved in the modulation of a number of biological processes. The
      molecular mechanisms explaining Id2 pleiotropic functions are poorly understood.
      Id2 and E2F4 are known to bind simultaneously to c-myc promoter. To study whether
      Id2 plays a global role on transcriptional regulation, we performed in vivo
      genome-wide ChIP/chip experiments for Id2 and E2F4 in adult mouse liver. An Id2
      containing complex was bound to a common sequence downstream from the TSS on a
      subset of 442 E2F4 target genes mainly related to cell development and chromatin
      structure. We found a positive correlation between Id2 protein levels and the
      expression of E2F4/Id2 targets in fetal and adult liver. Id2 protein stability
      increased in fetal liver by interaction with USP1 de-ubiquitinating enzyme, which
      was induced during development. In adult liver, USP1 and Id2 levels dramatically
      decreased. In differentiated liver tissue, when Id2 concentration was low,
      E2F4/Id2 was bound to the same region as paused Pol II and target genes remained
      transcriptionally inactive. Conversely, in fetal liver when Id2 levels were
      increased, Id2 and Pol II were released from gene promoters and target genes up
      regulated. During liver regeneration after partial hepatectomy, we obtained the
      same results as in fetal liver. Our results suggest that Id2 might be part of a
      reversible development-related program involved in the paused-ON/OFF state of Pol
      II on selected genes that would remain responsive to specific stimuli. 

PMID- 24573696
TI  - Chimpanzee diet: phytolithic analysis of feces.
AB  - Most primate populations remain unobservable; therefore, researchers depend on
      the analyses of indirect evidence encountered at a study-site in order to
      understand their behavioral ecology. Diet can be determined through the analyses
      of scats or feeding remains encountered on-site. This allows aspects of their
      dietary repertoire to be established, which has implications both for
      conservation efforts (by locating food resources), and for understanding the
      evolution of hominin diet (if used as referential models). Macroscopic inspection
      of fecal samples is a common method applied to ascertain a primate population's
      diet. However, new approaches are required to identify food-items unrecognizable
      at this level. We applied a dry ash extraction method to fecal samples (N=50)
      collected from 10 adult chimpanzees in Kanyawara, Kibale National Park, Uganda
      and also to plant parts (N=66) from 34 species known to be included in the diet
      of this community of apes. We recovered phytoliths in 26 of the 34 plant species.
      Fifteen phytolith morphotypes were only detected in 14 plant species (termed
      "distinct" phytoliths). We used these distinct phytoliths to identify plant foods
      (i.e., that they were associated with) in fecal samples. We then validated
      findings by checking if the 10 chimpanzees had eaten parts of these plants ~24 hr
      prior to fecal sample collection; six plant species associated with five distinct
      phytoliths had been eaten. Finally, we compared plant foods identified in fecal
      samples from phytolith analyses with plants that had been identified from
      macroscopic inspection of the same fecal samples. Findings from phytolith
      analyses corroborate with those from macroscopic inspection by expanding the
      total number of plant species identified per fecal sample (i.e., we identified
      certain plant parts that remained unrecognizable at macroscopic level). This
      study highlights the potential of phytolith analyses of feces to increase our
      knowledgebase of the dietary repertoire of primate populations.

PMID- 24573693
TI  - Role of cytosolic phospholipase A2 in oxidative and inflammatory signaling
      pathways in different cell types in the central nervous system.
AB  - Phospholipases A(2) (PLA(2)s) are important enzymes for the metabolism of fatty
      acids in membrane phospholipids. Among the three major classes of PLA(2)s in the
      mammalian system, the group IV calcium-dependent cytosolic PLA(2) alpha
      (cPLA(2)alpha) has received the most attention because it is widely expressed in
      nearly all mammalian cells and its active participation in cell metabolism.
      Besides Ca(2+) binding to its C2 domain, this enzyme can undergo a number of cell
      specific post-translational modifications, including phosphorylation by protein
      kinases, S-nitrosylation through interaction with nitric oxide (NO), as well as
      interaction with other proteins and lipid molecules. Hydrolysis of phospholipids
      by cPLA(2) yields two important lipid mediators, arachidonic acid (AA) and
      lysophospholipids. While AA is known to serve as a substrate for cyclooxygenases
      and lipoxygenases, which are enzymes for the synthesis of eicosanoids and
      leukotrienes, lysophospholipids are known to possess detergent-like properties
      capable of altering microdomains of cell membranes. An important feature of
      cPLA(2) is its link to cell surface receptors that stimulate signaling pathways
      associated with activation of protein kinases and production of reactive oxygen
      species (ROS). In the central nervous system (CNS), cPLA(2) activation has been
      implicated in neuronal excitation, synaptic secretion, apoptosis, cell-cell
      interaction, cognitive and behavioral function, oxidative-nitrosative stress, and
      inflammatory responses that underline the pathogenesis of a number of
      neurodegenerative diseases. However, the types of extracellular agonists that
      target intracellular signaling pathways leading to cPLA(2) activation among
      different cell types and under different physiological and pathological
      conditions have not been investigated in detail. In this review, special emphasis
      is given to metabolic events linking cPLA(2) to activation in neurons,
      astrocytes, microglial cells, and cerebrovascular cells. Understanding the
      molecular mechanism(s) for regulation of this enzyme is deemed important in the
      development of new therapeutic targets for the treatment and prevention of
      neurodegenerative diseases.

PMID- 24573699
TI  - Easily accessible and highly tunable bisphosphine ligands for asymmetric
      hydroformylation of terminal and internal alkenes.
AB  - An efficient methodology for synthesizing a small library of easily tunable and
      sterically bulky ligands for asymmetric hydroformylation (AHF) has been reported.
      Five groups of alkene substrates have been tested with excellent conversions,
      moderate-to-excellent regio- and enantioselectivities. Among the best result of
      the reported literature, application of ligand 1 c in the highly selective AHF of
      the challenging substrate 2,5-dihydrofuran yielded almost one isomer in up to 99
      % conversion along with enantiomeric excesses (ee) of up to 92 %. Highly
      enantioselective AHF of dihydropyrrole substrates is achieved using the same
      ligand, with up to 95 % ee and up to >1:50 beta-isomer/alpha-isomer ratio. 

PMID- 24573695
TI  - ZEB2-transgene expression in the epidermis compromises the integrity of the
      epidermal barrier through the repression of different tight junction proteins.
AB  - Epithelial homeostasis within the epidermis is maintained by means of multiple
      cell-cell adhesion complexes such as adherens junctions, tight junctions, gap
      junctions, and desmosomes. These complexes co-operate in the formation and the
      regulation of the epidermal barrier. Disruption of the epidermal barrier through
      the deregulation of the above complexes is the cause behind a number of skin
      disorders such as psoriasis, dermatitis, keratosis, and others. During epithelial
      to-mesenchymal transition (EMT), epithelial cells lose their adhesive capacities
      and gain mesenchymal properties. ZEB transcription factors are key inducers of
      EMT. In order to gain a better understanding of the functional role of ZEB2 in
      epidermal homeostasis, we generated a mouse model with conditional overexpression
      of Zeb2 in the epidermis. Our analysis revealed that Zeb2 expression in the
      epidermis leads to hyperproliferation due to the combined downregulation of
      different tight junction proteins compromising the epidermal barrier. Using two
      epidermis-specific in vivo models and in vitro promoter assays, we identified
      occludin as a new Zeb2 target gene. Immunohistological analysis performed on
      human skin biopsies covering various pathogeneses revealed ZEB2 expression in the
      epidermis of pemphigus vulgaris. Collectively, our data support the notion for a
      potential role of ZEB2 in intracellular signaling of this disease. 

PMID- 24573700
TI  - Analysis of YouTube as a source of information for West Nile Virus infection.
AB  - INTRODUCTION: A major outbreak of West Nile Virus was seen last year in different
      parts of the United States. Adequate dissemination of correct information about
      the disease would have helped decrease its spread and the associated panic in the
      general population. In this study, we looked into the use of YouTube as a
      resource for providing information about West Nile Virus infection. OBJECTIVE:
      This study aims to identify and evaluate YouTube as resource for providing
      information on West Nile Virus infection to the general public. METHODS: YouTube
      was searched on November 25, 2012, using the keywords West Nile Virus epidemic,
      West Nile Virus infection, and West Nile Virus prevention for videos uploaded in
      the past 6 months containing relevant information about the disease. The videos
      were classified as useful, misleading, or as news updates based on the type of
      information contained. Total viewership, number of days since upload, total
      duration of videos, and source of upload were noted. RESULTS: A total of 106
      videos with information on West Nile Virus infection were included in the study,
      with 79.24% having useful information about the disease. Among the useful videos,
      51/84 (60.71%) had information on disease prevention, and 29/84 (34.52%)
      contained information on news and research updates. The majority of these videos
      were uploaded by individuals (54.6%) or news agencies (41.8 %). Healthcare
      agencies contributed only 3.4 % of the total videos. Even though the useful
      videos represented 72% of all videos, there was significantly higher total
      viewership and viewership per day for the non-useful videos (P<0.05).
      CONCLUSIONS: YouTube may be a significant resource for dissemination of
      information on public health issues like West Nile virus infection and should be
      targeted by healthcare agencies for this use. The major drawback of this medium
      is lack of verification by authorized healthcare professionals before these
      videos are made available for viewing by the community. Hence, a strict caution
      should be exercised in obtaining the information from unauthorized videos posted
      on YouTube.

PMID- 24573702
TI  - Paroxysmal paralytic attacks secondary to excessive cola consumption.
AB  - We report a rare case of cola-induced hypokalemia presenting as recurrent attacks
      of lower extremity weakness and falls. Excessive consumption of cola-based drinks
      has been associated with dental enamel erosion, obesity, and diabetes. There are
      very few published cases depicting the correlation between cola drinks and
      hypokalemic manifestations. In our patient an extensive workup was performed, and
      common causes were ruled out before making the diagnosis of cola-induced
      hypokalemia. Improvement in the patient's symptoms and electrolyte levels after
      reducing the consumption of cola-based drinks further confirmed our diagnosis.
      This case also emphasizes the importance of obtaining a detailed history and
      consideration of broad differential diagnoses in identifying uncommon but
      reversible etiologies. 

PMID- 24573701
TI  - SNPs previously associated with Dupuytren's disease replicated in a North
      American cohort.
AB  - OBJECTIVE: Dupuytren's disease is a progressive fibrosis of the hand that often
      results in debilitating flexion contractures. Its etiology is not completely
      understood but likely involves both genetic and environmental factors. A recent
      study performed in Europe identified DNA variants that associate with Dupuytren's
      disease. Given the likelihood for genetic variation among populations, we planned
      to validate the genetic variants identified by this study in a North American
      population. METHODS: In the Marshfield Clinic's Personalized Medicine Research
      Project, 296 cases with Dupuytren's disease were identified and matched 3-to-1 to
      controls without Dupuytren's disease. Clinical data were abstracted from the
      electronic medical record. The top 12 single nucleotide polymorphisms (SNPs) from
      the European study were selected and tested in a multiplex assay using the
      MassArray Analyzer 4 (Sequenom, Inc., San Diego, CA). Differences in allele
      frequency were determined, and variants with a P value of <0.004 were considered
      significant. RESULTS: We replicated 5 of the 12 SNPs previously reported to be
      associated with Dupuytren's disease. CONCLUSION: Our findings support a role for
      the Wnt signaling pathway in the development of Dupuytren's disease, and suggest
      that further study of this pathway may result in early diagnosis and non-surgical
      treatments for Dupuytren's disease.

PMID- 24573703
TI  - Is it time for the Cochrane Collaboration to reconsider its meta-analysis
      methodology?

PMID- 24573706
TI  - The use of (99m)Tc-phytate for sentinel node mapping in melanoma, breast cancer
      and vulvar cancer: a study of 100 cases.
AB  - Sentinel node mapping reduces surgical morbidity and allows the use of more
      accurate tumour staging techniques. Radionuclide studies are preferentially
      performed using small colloids, which have limited availability in our country.
      The possibility of using phytate for sentinel node mapping was raised because of
      the similarity between its biodistribution and that of nanocolloids in the
      reticulo-endothelial system. In this paper we evaluated the use of (99m)Tc
      phytate for sentinel node mapping, correlating the histopathological results with
      the status of the rest of the lymph node chain in different malignant tumours. A
      total of 100 patients were studied. group 1 consisted of 62 patients with breast
      cancer, group 2 of 20 patients with melanoma and group 3 of 18 patients with
      vulvar carcinoma. Lymph node scintigraphy was carried out after injecting (99m)Tc
      phytate subdermally, and the sentinel node projection was marked on the skin.
      After 18-24 h, intraoperative sentinel node localisation was performed using a
      gamma probe (combined with visual localisation using patent blue dye) in 75
      patients, and lymph node dissection was then carried out. Radionuclide
      scintigraphy identified the sentinel node in 98% of all studies. Intraoperative
      detection using the gamma probe was equally efficient: group 1=93% (38/41), group
      2=95% (18/19) and group 3=100% (15/15). The sentinel node was involved in 41%,
      31% and 20% of cases in groups 1, 2 and 3, respectively. Among the patients with
      positive nodes, the sentinel node was the only one affected in 53% of group 1,
      50% of group 2 and 67% of group 3 cases. The method's negative predictive value
      was 91% in group 1 and 100% in the other groups. One false-negative study
      occurred in a patient who had a multifocal tumour and an intraparenchymatous
      lymph node; another occurred in a patient with a macroscopically affected node
      found during surgery. There were no side-effects related to the (99m)Tc-phytate.
      It is concluded that scintigraphic and intraoperative sentinel node
      identification was satisfactorily performed using (99m)Tc-phytate. The results
      were comparable to those previously described in the literature using other
      radiopharmaceuticals. Easy availability and low cost justify the use of phytate
      in our practice. 

PMID- 24573707
TI  - Erratum to: Peptide radiopharmaceuticals for diagnosis and therapy.

PMID- 24573704
TI  - The role of aspirin in the prevention of cardiovascular disease.
AB  - Aspirin therapy is well-accepted as an agent for the secondary prevention of
      cardiovascular events and current guidelines also define a role for aspirin in
      primary prevention. In this review, we describe the seminal trials of aspirin use
      in the context of current guidelines, discuss factors that may influence the
      effectiveness of aspirin therapy for cardiovascular disease prevention, and
      briefly examine patterns of use. The body of evidence supports a role for aspirin
      in both secondary and primary prevention of cardiovascular events in selected
      population groups, but practice patterns may be suboptimal. As a simple and
      inexpensive prophylactic measure for cardiovascular disease, aspirin use should
      be carefully considered in all at-risk adult patients, and further measures,
      including patient education, are necessary to ensure its proper use. 

PMID- 24573710
TI  - Limiting electric fields of HVDC overhead power lines.
AB  - As a consequence of the increased use of renewable energy and the now long
      distances between energy generation and consumption, in Europe, electric power
      transfer by high-voltage (HV) direct current (DC) overhead power lines gains
      increasing importance. Thousands of kilometers of them are going to be built
      within the next years. However, existing guidelines and regulations do not yet
      contain recommendations to limit static electric fields, which are one of the
      most important criteria for HVDC overhead power lines in terms of tower design,
      span width and ground clearance. Based on theoretical and experimental data, in
      this article, static electric fields associated with adverse health effects are
      analysed and various criteria are derived for limiting static electric field
      strengths.

PMID- 24573709
TI  - Interstitial granulomatous dermatitis associated with myelodysplastic syndrome -
      complete clearance under therapy with 5-azacytidine.

PMID- 24573711
TI  - The National Commission on Physician Payment Reform: recalibrating fee-for
      service and transitioning to fixed payment models.

PMID- 24573712
TI  - Improving the quality and lowering the cost of health care: Medicare reforms from
      the National Commission on Physician Payment Reform.

PMID- 24573713
TI  - The national physician payment commission recommendation to eliminate fee-for
      service payment: balancing risk, benefit, and efficiency in bundling payment for
      care.

PMID- 24573714
TI  - Hospitalist career decisions among internal medicine residents.
AB  - BACKGROUND: Hospital medicine is a rapidly growing field of internal medicine.
      However, little is known about internal medicine residents' decisions to pursue
      careers in hospital medicine (HM). OBJECTIVE: To identify which internal medicine
      residents choose a career in HM, and describe changes in this career choice over
      the course of their residency education. DESIGN: Observational cohort using data
      collected from the annual Internal Medicine In-Training Examination (IM-ITE)
      survey. PARTICIPANTS: 16,781 postgraduate year 3 (PGY-3) North American internal
      medicine residents who completed the annual IM-ITE survey in 2009-2011, 9,501 of
      whom completed the survey in all 3 years of residency. MAIN MEASURES: Self
      reported career plans for individual residents during their postgraduate year 1
      (PGY-1), postgraduate year 2 (PGY-2) and PGY-3. KEY RESULTS: Of the 16,781
      graduating PGY-3 residents, 1,552 (9.3 %) reported HM as their ultimate career
      choice. Of the 951 PGY-3 residents planning a HM career among the 9,501 residents
      responding in all 3 years, 128 (13.5 %) originally made this decision in PGY-1,
      192 (20.2 %) in PGY-2, and 631 (66.4 %) in PGY-3. Only 87 (9.1 %) of these 951
      residents maintained a career decision of HM during all three years of residency
      education. CONCLUSIONS: Hospital medicine is a reported career choice for an
      important proportion of graduating internal medicine residents. However, the
      majority of residents do not finalize this decision until their final year.

PMID- 24573715
TI  - Molecular therapies in hepatocellular carcinoma: what can we target?
AB  - Numerous signaling pathways, such as Ras/Raf/MAPK, have been implicated in
      hepatic carcinogenesis. There are at least 35 combination therapy studies for
      advanced stage hepatocellular carcinoma (HCC) ongoing, and numerous reagents are
      being tested targeting novel signaling cascades. The management of HCC has
      changed substantially in recent times, and the successful development of
      sorafenib has prompted further expansion on molecular targeted therapies to
      potentially inhibit different pathways in hepatocarcinogenesis. 

PMID- 24573716
TI  - Racial disparities in the proportion of current, unresolved hepatitis C virus
      infections in the United States, 2003-2010.
AB  - BACKGROUND: The hepatitis C virus (HCV) antibody test alone does not distinguish
      current from resolved infections. AIM: The study aimed to describe the percentage
      of current HCV infection, defined by HCV RNA positivity, among those tested
      positive for anti-HCV, and to examine characteristics of those with current
      infection. METHODS: Using nationally representative data from the 2003 to 2010
      National Health and Nutrition Examination Surveys, descriptive analyses and
      regressions were performed on data from anti-HCV-positive adults aged >= 40
      years. RESULTS: Of 13,909 participants examined, 304 were anti-HCV-positive. Of
      these, 238 or 75.3% [95% confidence interval (CI) 67.5-81.8%] had detectable
      viral RNA. The percentage of current, unresolved HCV infection was highest among
      non-Hispanic Blacks (91.1%) and lowest among those with a college education
      (57.3%). In multivariate analyses, non-Hispanic Blacks were more likely to have
      current HCV infection compared to non-Hispanic Whites (adjusted odds ratio 3.9,
      95% CI 1.6-9.2). Among persons with current HCV infection, most had elevated
      alanine aminotransferase (56.5%) or aspartate aminotransferase (71.8%) levels,
      but only 35.3% reported having been diagnosed with any abnormal liver conditions.
      Excessive alcohol drinking was reported by 27.3% of participants with current HCV
      infection. CONCLUSIONS: Among adults aged >= 40 years who had ever been infected
      with HCV, approximately three-quarters had current, unresolved HCV infection. Non
      Hispanic Blacks were more likely to have current infection than non-Hispanic
      Whites. The majority of those with current infection had abnormal liver function
      tests but had not received appropriate diagnoses. Many currently infected persons
      would benefit from lifestyle modifications to avoid the multiplicative effect of
      alcohol on HCV infection.

PMID- 24573717
TI  - Isoniazid hepatotoxicity requiring liver transplantation.

PMID- 24573718
TI  - Comparison of the outcomes of endoscopic ultrasound based on community hospital
      versus tertiary academic center settings.
AB  - OBJECTIVE: Endoscopic ultrasound (EUS) is an established tool in the management
      of gastrointestinal diseases. The majority of EUS procedures are performed in
      tertiary care hospitals but the technology has also disseminated to community
      hospitals. The data from community hospitals are limited and there are no
      published studies comparing EUS-fine needle aspiration (FNA) outcomes in
      community versus tertiary settings. Our objective is to compare EUS procedures
      performed in these two separate settings. METHODS: EUS procedures performed for
      pancreatobiliary indications in an academic tertiary care hospital and a
      community hospital were retrospectively reviewed and compared. The patient
      demographics, procedure time, procedure indications, FNA performed, pass counts,
      needle size, rapid onsite evaluation (ROSE) and final cytological diagnosis were
      compared between the two centers. Cytological diagnosis was categorized as
      satisfactory and unsatisfactory samples. RESULTS: There was no significant
      difference in patient age, gender, indications, procedure time, FNA performed,
      needle size, or pass counts between the tertiary hospital (n = 361) and community
      hospital (n = 119). ROSE was a significant determinant factor for adequacy of
      sample. There was a positive linear relationship between adequacy of the sample
      and number of pass counts. After performing a logistic regression and adjusting
      for target site, the overall odds of having an unsatisfactory specimen were not
      significantly different at the two centers (OR 0.51, CI 0.23-1.17, p = 0.11).
      Percentages of unsatisfactory samples were not significantly different at the two
      centers for solid lesions (7.4 vs. 3.1%, p = 0.33), cysts (33.3 vs. 23.8%, p =
      0.31,) or lymph nodes (25.0 vs. 0%, p = 0.063). CONCLUSION: Cytological yield of
      EUS-FNA in a community hospital is similar to that of a tertiary hospital.
      Community hospitals can provide EUS services with reasonable success.

PMID- 24573720
TI  - Morphologic changes of dendritic spines of striatal neurons in the levodopa
      induced dyskinesia model.
AB  - Maladaptive plasticity at corticostriatal synapses plays an important role in the
      development of levodopa-induced dyskinesia. Recently, it has been shown that
      synaptic plasticity is closely linked to morphologic changes of dendritic spines.
      To evaluate morphologic changes of dendritic spines of two types of striatal
      medium spiny neurons, which project to the internal segment of globus pallidus or
      the external segment of globus pallidus, in the levodopa-induced dyskinesia
      model, we used 6-hydroxydopamine-lesioned rats chronically treated with levodopa.
      Dendritic spines were decreased and became enlarged in the direct pathway neurons
      of the model of levodopa-induced dyskinesia. The same levodopa treatment to
      normal rats, in which no dyskinesia was observed, also induced enlargement of
      dendritic spines, but not a decrease in density of spines in the direct pathway
      neurons. These results suggest that a loss and enlargement of dendritic spines in
      the direct pathway neurons plays important roles in the development of levodopa
      induced dyskinesia.

PMID- 24573723
TI  - A disulfide-constrained miniprotein with striking tumor-binding specificity
      developed by ribosome display.

PMID- 24573724
TI  - Highly efficient dehydrogenation of formic acid over a palladium-nanoparticle
      based Mott-Schottky photocatalyst.

PMID- 24573719
TI  - Increased gap density predicts weakness of the epithelial barrier in vivo by
      confocal laser endomicroscopy in indomethacin-induced enteropathy.
AB  - BACKGROUND AND AIMS: The intestinal epithelial barrier plays an important role in
      the pathogenesis of non-steroidal anti-inflammatory drug-induced enteropathy, and
      its disruption is often associated with increased cell shedding. The purpose of
      this report is to observe the gap density in indomethacin-induced small
      intestinal damage by confocal laser endomicroscopy (CLE) and to investigate the
      mechanisms involved in this process and how mucosal protectants improve
      intestinal epithelial barrier dysfunction. CLE is expected to provide a new way
      for evaluating non-steroidal anti-inflammatory drugs-induced enteropathy in
      humans and assessing drug efficacy. METHODS: Using the new technique of CLE, we
      established a method to evaluate, in real time, intestinal damage after the
      administration of indomethacin in Wistar rats by investigating the gap density in
      the small intestine. The mucosal protectant teprenone and acid-suppressant
      rabeprazole were then given by gavage before and after the administration of
      indomethacin, and the mechanisms affecting the intestinal epithelial barrier were
      investigated. RESULTS: Using CLE, gaps could be clearly observed and easily
      distinguished from goblet cells. Gap density was increased after the
      administration of indomethacin. During this process, the expression of tumor
      necrosis factor-alpha, nuclear factor-kappaB, and caspase-3 was up-regulated and
      the expression of tight junctions was down-regulated, which led to the damage of
      the epithelial barrier. Teprenone and rabeprazole could intervene in this pathway
      and protect the integrity of the epithelial barrier. CONCLUSIONS: CLE can be
      objective, accurate, and real time in investigating gap density. Teprenone and
      rabeprazole can prevent indomethacin-induced intestinal lesions and protect the
      epithelial barrier by intervening in the tumor necrosis factor-alpha pathway. Gap
      density was expected to be an indicator of evaluating intestinal inflammation and
      drug efficacy.

PMID- 24573725
TI  - Rhodium(III)-catalyzed azidation and nitration of arenes by C-H activation.

PMID- 24573726
TI  - RASSF10 is an epigenetically silenced tumor suppressor in gastric cancer.
AB  - To better understand the role of the N-Terminal Ras association domain family
      (RASSF) genes in the development of gastric cancer, we examined the expression of
      RASSF7 and RASSF10 and RASSF10 methylation in gastric cancer. We found that
      RASSF10 expression was lost in six gastric cancer cell lines, and was rescued by
      a DNA demethylating agent and a histone deacetylase inhibitor. However, RASSF7
      expression was strong in four cancer cell lines as well as in 87% of primary
      gastric cancer tissues. In contrast, RASSF7 expression was moderate in the GES-1
      cell line and negative in 33.3% of the corresponding non-cancerous tissues.
      Analysis of RASSF10 methylation by methylation-specific PCR (MSP) and sequencing
      revealed that the methylation frequency in primary gastric carcinoma tissues was
      significantly higher compared to that in adjacent non-carcinoma tissues (61.6 vs.
      38.4%; p<0.01). The methylation frequency in the tumor with invasion depth at T3
      and T4 was significantly higher compared to that with invasion depth at T1 and T2
      (67.1 vs. 37.5%; p<0.05). Hypermethylation of RASSF10 was found in the patients
      with lymph node metastasis, compared to those with unaffected lymph nodes (68.8
      vs. 40.9%; p<0.05). Among the 4 gross types of the Borrmann classification, i.e.
      EGC, Borrmann I, Borrmann II, Borrmann III and Borrmann IV, the last one was more
      frequently methylated (85.7 vs. 56.9%; p<0.05). The present study revealed that
      RASSF10 is an epigenetically silenced gene involved in tumor invasion and
      metastasis in gastric cancer, suggesting that the methylation status of RASSF10
      may be a useful indicator to predict the malignant degree of gastric cancer.

PMID- 24573727
TI  - Colorectal cancer awareness issue.

PMID- 24573728
TI  - Colonic adenoma detection and differentiation - does technology improve efficacy?

PMID- 24573729
TI  - Quality reporting - finally achievable?

PMID- 24573730
TI  - Carbon dioxide insufflation can significantly reduce toilet use after
      colonoscopy: a double-blind randomized controlled trial.
AB  - BACKGROUND AND STUDY AIMS: Carbon dioxide (CO2) insufflation during colonoscopy
      can significantly decrease abdominal pain and bloating after the procedure, but
      its impact on the frequency and duration of toilet use remains unknown. The aim
      of this study was to assess the impact of CO2 insufflation on toilet use after
      screening colonoscopy. METHODS: From 138 average-risk individuals who underwent
      screening colonoscopy during March to August 2013, 120 were enrolled and
      randomized to receive either CO2 or air insufflation at colonoscopy. Both the
      colonoscopist and participant were blinded to the type of gas used. Abdominal
      pain and distension were assessed using a visual analog scoring system. The
      frequency and duration of toilet visits during a 2-hour postcolonoscopy period
      were recorded using a radiofrequency identification system. RESULTS: Baseline
      characteristics were similar in both groups in terms of age, sex, and procedure
      time. In the 2 hours after colonoscopy, 50 participants (83 %) in the air group
      and 18 participants (30 %) in the CO2 group (P < 0.001) used the toilet at least
      once. The mean (+/- SD) duration of each toilet visit was 5.93 +/- 4.65 minutes
      in the air group and 1.53 +/- 2.84 minutes in the CO2 group (P < 0.001). The
      abdominal discomfort score was lower in the CO2 group than in the air group both
      at the end of the colonoscopy (P < 0.001) and 2 hours later (P < 0.001).
      CONCLUSION: Insufflation with CO2 can significantly reduce abdominal discomfort
      and toilet use after colonoscopy. Use of this technique may help reduce patient
      burden and allow more efficient use of space in the endoscopy unit.

PMID- 24573731
TI  - L-menthol improves adenoma detection rate during colonoscopy: a randomized trial.
AB  - BACKGROUND AND STUDY AIMS: Colonoscopy is one of the most reliable methods for
      the detection of colorectal neoplasms. However, colonic peristalsis during
      colonoscopy results in some neoplastic lesions being hidden from view and
      commonly requires an intravenous or intramuscular injection of antispasmodic
      agents, which may sometimes causes unexpected adverse reactions. The aim of this
      study was to evaluate the efficacy of L-menthol spray as an antiperistaltic agent
      and its effect on adenoma detection. PATIENTS AND METHODS: This was a
      prospective, randomized, single-blind placebo-controlled trial. A total of 226
      patients who were scheduled to undergo colonoscopy were randomly assigned to
      receive either 20 mL of 1.6 % L-menthol (n = 118) or placebo (n = 108). Both
      treatments were sprayed locally onto the colonic mucosa via an endoscope. The
      adenoma detection rate (ADR) and the proportion of patients with no peristalsis
      were the primary and secondary outcomes, respectively. RESULTS: The ADR was
      significantly higher in the L-menthol group than in the placebo group (60.2 % vs.
      42.6 %; P = 0.0083). The proportion of patients with no peristalsis after
      treatment with L-menthol was significantly higher than in the placebo group (71.2
      % vs. 30.9 %; P < 0.0001). There were no adverse effects in either group.
      CONCLUSIONS: The results suggest that the suppression of colonic peristalsis by L
      menthol sprayed directly onto the colonic mucosa improves the ADR. CLINICAL TRIAL
      REGISTRATION: ID: UMIN 000007972.

PMID- 24573732
TI  - Endoscopic characterization of sessile serrated adenomas/polyps with and without
      dysplasia.
AB  - BACKGROUND AND STUDY AIMS: Sessile serrated adenomas/polyps (SSA/Ps) are
      precursors of colorectal cancer (CRC), but their endoscopic detection can be
      difficult. We therefore examined the endoscopic characteristics of SSA/Ps with
      and without dysplasia in a cross-sectional study. PATIENTS AND METHODS: We
      reviewed clinical, endoscopic, and histopathologic data from patients undergoing
      colonoscopy between February 2008 and February 2012. We categorized colorectal
      polyps according to anatomic site, size, and shape, and classified serrated
      polyps using the World Health Organization (WHO) classification. Multiple
      logistic regression analyses examined potential differences regarding site, size,
      and shape between SSA/Ps and colorectal adenomas (overall and advanced only).
      RESULTS: We examined 7433 patients (mean age 59 years, 45.9 % men) with 5968
      colorectal polyps. In total, we found 170 SSA/Ps (170/5968, 2.9 %), including 63
      SSA/Ps with dysplasia (1.1 %) and 107 SSA/Ps without dysplasia (1.8 %). Compared
      with SSA/Ps with dysplasia, SSA/Ps without dysplasia were more often proximally
      located (odds ratio [OR] 3.3, 95 % confidence interval [95 %CI] 1.7 - 6.4), but
      less often < 6 mm in size (OR 0.6, 95 %CI 0.3 - 1.1). No significant differences
      were found regarding location between SSA/Ps with dysplasia and advanced adenomas
      (proximal colon, 47.6 % vs. 40.1 %). However, SSA/Ps with dysplasia were more
      often < 6 mm in size than advanced adenomas (OR 0.3, 95 %CI 0.2 - 0.5). Of the 63
      dysplastic SSA/Ps, 6 (9.5 %) contained high grade dysplasia, but none invasive
      carcinoma. CONCLUSIONS: SSA/Ps with dysplasia are frequently < 6 mm in size,
      located throughout the colon and 9.5 % of them contain high grade dysplasia.
      These findings underscore the importance of high quality colonoscopic examination
      to maximize protection against CRC.

PMID- 24573734
TI  - Pseudoaneurysm caused by a self-expandable metal stent: a report of three cases.
AB  - We present three cases of pseudoaneurysm caused by self-expandable metal stents
      that formed arteriobiliary fistulas and caused hemobilia. Diagnoses were made on
      the basis of dynamic computed tomography or angiography. One patient died because
      of bleeding and cholangitis, whereas the others were successfully treated by
      transarterial embolization. 

PMID- 24573735
TI  - Is capsule endoscopy a useful modality for the emergency triage of upper
      gastrointestinal hemorrhage?

PMID- 24573737
TI  - Do depressive symptoms in male and female adolescents predict unintended births
      in emerging adulthood?
AB  - Unintended birth and mental health are major public health problems in the United
      States. To date, little research has examined the relationship between depressive
      symptoms and unintended births, and no research has examined this relationship
      among men. Data from the National Longitudinal Survey of Adolescent Health (N =
      14,271) were used to examine the relationship between depressive symptoms among
      females and males in adolescence and unintended first birth in emerging
      adulthood. Respondents who reported higher levels of depressive symptoms in
      adolescence were more likely to report an unintended birth (OR 1.93, p < 0.001)
      compared with respondents who did not have children. They were also more likely
      to report an unintended birth compared with respondents who had an intended birth
      (OR 1.28, p < 0.05). The relationship between adolescent depressive symptoms and
      unintended birth remained significant, controlling for background variables, and
      it did not differ by gender. Adolescent depressive symptoms are associated with
      unintended birth in emerging adulthood. Thus, policies designed to treat
      depressive symptoms in adolescence may be effective in reducing unintended
      pregnancy among young adults.

PMID- 24573738
TI  - Vitamin D and systemic lupus erythematosus: state of the art.
AB  - Systemic lupus erythematosus (SLE) is a systemic inflammatory disease associated
      with genetic, environmental, hormonal, and immunological factors. One of these
      factors is vitamin D deficiency. Vitamin D plays many roles in the immune system.
      Several studies have suggested a potential role in the development of autoimmune
      diseases. SLE patients have low serum levels of vitamin D, which increase the
      possibility of an association between vitamin deficiency and disease onset and
      evolution. This review of the literature presents an analysis of the aspects
      related to the immunoregulatory effects of vitamin D and its importance for SLE,
      as well as the recommendations for vitamin D supplementation in these patients. 

PMID- 24573739
TI  - Ultrasonographic measurement of femoral cartilage thickness in acromegalic
      patients.
AB  - Joint involvement is one of the most frequent clinical complications of
      acromegaly. The aim of this study was to evaluate the femoral cartilage
      thicknesses of acromegalic patients using ultrasound (US). Sixty-two patients
      diagnosed with acromegaly (30 F, 32 M) were included. Patients' demographic and
      clinical characteristics were recorded. The thickness of the femoral articular
      cartilage was measured using a 6- to 18-MHz linear probe. Measurements were
      performed bilaterally from three points (medial condyle, intercondylar area, and
      lateral condyle). Of the patients, 14 (22.5 %) reported pain in the knee joints.
      A significantly higher femoral articular cartilage thickness was determined in
      the patients compared with the controls (all parameters, p < 0.001). US
      measurements results from all points were consistent, but these values were not
      correlated with levels of growth hormone (GH) and insulin-like growth factor-1
      (IGF-1). Analysis of acromegaly patients as active (n = 37) or inactive (n = 25)
      revealed no significance with respect to femoral cartilage thickness. Acromegalic
      patients seem to have thicker femoral articular cartilages irrespective of
      disease activity state. 

PMID- 24573740
TI  - General and food-specific inhibitory deficits in binge eating disorder.
AB  - OBJECTIVE: To investigate behavioral inhibition in individuals with binge eating
      disorder (BED) compared with overweight and obese individuals without BED (No
      BED). METHOD: Participants with BED (n = 31) and the weight-matched No-BED group
      (n = 29) completed an inhibitory control task (stop-signal task, SST) with food
      and neutral stimuli. RESULTS: The BED group needed more time to stop an ongoing
      response, as indicated by increased stop signal reaction time (SSRT) relative to
      the No-BED group. Additionally, compared with the No-BED group, the BED group
      displayed more difficulty inhibiting responses elicited by food stimuli. The
      deficits in behavioral response inhibition were also found to be related to the
      severity of reported symptoms. DISCUSSION: There is a general deficit in late
      stage behavioral inhibition in BED, and this may be particularly pronounced in
      the context of food stimuli.

PMID- 24573742
TI  - Pd-catalyzed decarboxylative cross-coupling of 2-carboxyazine N-oxides with
      various (hetero)aryl halides.
AB  - Decarboxylative cross-coupling reactions of substituted 2-carboxyazine N-oxides,
      with a variety of (hetero)aryl halides, by bimetallic Pd(0)/Cu(I) and Pd(0)/Ag(I)
      catalysis are reported. Two possible pathways, a conventional bimetallic
      catalyzed decarboxylative arylation, as well as a protodecarboxylative/direct C-H
      arylation sequence have been considered. These methods provide the first general
      decarboxylative arylation methodology for the 2-carboxyazine series.

PMID- 24573741
TI  - Paclitaxel-exposed ovarian cancer cells induce cancer-specific CD4+ T cells after
      doxorubicin exposure through regulation of MyD88 expression.
AB  - Ovarian cancer has the highest mortality rate among gynecological malignancies
      due to high chemoresistance to the combination of platinum with taxane.
      Immunotherapy against ovarian cancer is a promising strategy to develop from
      animal-based cancer research. We investigated changes in the immunogenicity of
      paclitaxel-exposed ovarian cancer cells following exposure to other
      chemotherapeutic drugs. Murine ovarian surface epithelial cells (MOSECs) showed
      some resistance to paclitaxel, a first-line therapy for ovarian cancer. However,
      MOSECs pre-exposed to paclitaxel died through apoptosis after incubation with
      doxorubicin or cisplatin for 2 h. Injected into mice, the paclitaxel-exposed
      MOSECs post-treated with doxorubicin induced more MOSEC-specific CD4(+) T cells
      and extended survival for a greater time than MOSECs treated with paclitaxel
      alone; and bone marrow-derived dendritic cells (BMDCs) expressed higher levels of
      co-stimulatory molecules and produced IL-12 after co-culture with paclitaxel
      exposed MOSECs treated with doxorubicin. We also observed that in paclitaxel
      exposed MOSECs treated with doxorubicin, but not cisplatin, the expression of
      MyD88 and related target proteins decreased compared to paclitaxel-exposed MOSECs
      only, while in BMDCs co-cultured with these MOSECs the expression of myeloid
      differentiation primary response gene 88 (MyD88) increased. These findings
      suggest that paclitaxel pre-exposed cancer cells treated with doxorubicin can
      induce significant apoptosis and a therapeutic antitumor immune response in
      advanced ovarian cancer.

PMID- 24573745
TI  - Th17 cells play a critical role in the development of experimental Sjogren's
      syndrome.
AB  - OBJECTIVE: Although Th17 cells have been increasingly recognised as an important
      effector in various autoimmune diseases, their function in the pathogenesis of
      Sjogren's syndrome (SS) remains largely uncharacterised. This study aims to
      determine the role of Th17 cells in the development of experimental SS (ESS).
      METHODS: The ESS was induced in wildtype and IL-17A knockout (IL-17 KO) C57BL/6
      mice immunised with salivary glands (SG) proteins. Phenotypic analysis of immune
      cells in the draining cervical lymph nodes (CLN) and SG was performed by flow
      cytometry and immunofluorescence microscopy. To determine the role of Th17 cells
      in ESS, immunised IL-17 KO mice were adoptively transferred with in vitro
      generated Th17 cells and monitored for SS development. The salivary flow rate was
      measured, whereas inflammatory infiltration and tissue destruction in SG were
      assessed by histopathology. RESULTS: SG protein-immunised mice developed overt SS
      symptoms with increased Th17 cells detected in CLN and within lymphocytic foci in
      inflamed SG. Notably, immunised IL-17 KO mice were completely resistant for SS
      induction, showing no evidence of disease symptoms and histopathological changes
      in SG. Adoptive transfer of Th17 cells rapidly induced the onset of ESS in
      immunised IL-17 KO mice with markedly reduced saliva secretion, elevated
      autoantibody production and pronounced inflammation and tissue damage in SG.
      CONCLUSIONS: Our findings have defined a critical role of Th17 cells in the
      pathogenesis of ESS. Further studies may validate Th17 cell as a potential target
      for treating SS.

PMID- 24573746
TI  - Mitochondrial control region variation in a Korean population sample.
AB  - Mitochondrial DNA (mtDNA) control region (16024-576) sequences were generated
      from 281 individuals from South Korea. Robotic liquid handling, a redundant
      sequencing strategy, and a series of quality control checks were implemented to
      ensure the high quality of the dataset. This population sample showed a low
      random match probability (0.25 %) and high genetic diversity (0.9933). The
      haplogroup breakdown was consistent with previous studies describing Korean mtDNA
      variation. The 224 unique haplotypes (33 shared) presented will supplement the
      data already publically available.

PMID- 24573743
TI  - A phase II open-label randomized multicenter trial of TSU-68 in combination with
      S-1 and oxaliplatin versus S-1 in combination with oxaliplatin in patients with
      metastatic colorectal cancer.
AB  - BACKGROUND: Colorectal cancer (CRC) is the fourth leading cause of cancer-related
      deaths worldwide. The combination of oxaliplatin-based treatments (oxaliplatin
      plus infusional 5-fluorouracil and leucovorin [FOLFOX] or oxaliplatin plus
      capecitabine [CapeOX]) and bevacizumab is a standard chemotherapy regimen for
      metastatic CRC (mCRC). However, several clinical studies that tested S-1 plus
      oxaliplatin (SOX) indicate that SOX is also a treatment option for mCRC. TSU-68
      is an oral compound that inhibits vascular endothelial growth factor receptor and
      platelet-derived growth factor receptor. The recommended dose of TSU-68 + SOX was
      previously determined in a phase I study of mCRC patients. The goal of this trial
      was to evaluate the efficacy of TSU-68 in combination with SOX. METHODS: This
      open-label multicenter randomized phase II trial was performed in Korea.
      Treatment-naive mCRC patients with a performance status of 0 or 1 were randomized
      in a 1:1 ratio to receive either TSU-68 + SOX or SOX alone. The primary endpoint
      was progression-free survival (PFS). RESULTS: A total of 105 patients (TSU-68 +
      SOX, 52 patients; SOX alone, 53 patients) were randomized. The median PFS was 7.0
      months in the TSU-68 + SOX group (hazard ratio [HR], 1.057) and 7.2 months in the
      SOX group (p = 0.8401). The most frequent grade 3 and 4 adverse events were
      thrombocytopenia (9.6 % [TSU-68 + SOX] vs. 26.4 % [SOX]), neutropenia (13.5 %
      [TSU-68 + SOX] vs. 15.1 % [SOX]), and anemia (3.8 % [TSU-68 + SOX] vs. 13.2 %
      [SOX]). We observed a difference between the 2 groups for all grades of anemia
      (15.4 % [TSU-68 + SOX] vs. 32.1 % [SOX]), diarrhea (30.8 % [TSU-68 + SOX] vs.
      47.2 % [SOX]), vomiting (50.0 % [TSU-68 + SOX] vs. 26.4 % [SOX]), and chromaturia
      (23.1 % [TSU-68 + SOX] vs. 0.0 % [SOX]). Analysis using a Cox proportional hazard
      model showed that baseline interleukin 6 (IL-6) levels were associated with a
      survival benefit of TSU-68 (p = 0.012). CONCLUSION: TSU-68 + SOX had a favorable
      safety profile. However, TSU-68 did not have a synergistic effect on the efficacy
      of SOX. The baseline serum IL-6 level could be a prognostic factor for TSU-68
      efficacy.

PMID- 24573748
TI  - MicroRNA-based therapy in cardiology.
AB  - The pathogenic role of noncoding microRNA (miR, miRNA) has been demonstrated for
      several disease conditions in the heart. The underlying molecular mechanisms have
      been deciphered for numerous miRs that are deregulated as a result of cardiac
      stress. Innovative therapeutic strategies based on antifibrotic,
      antihypertrophic, or proangiogenic effects of miRNAs are being currently
      developed to improve the function of the failing heart. Identifying a safe and
      efficient miR-based strategy remains challenging, yet these novel approaches
      offer enormous potential for the treatments for heart failure. In this review we
      highlight the latest development in the cardiac miRNA field. 

PMID- 24573749
TI  - Acute renal failure in tetanus: authors' reply.

PMID- 24573750
TI  - Soren Kierkegaard (1813-55): a bicentennial pathographical review.
AB  - Researchers in the fields of psychology, psychiatry, medicine and theology have
      made exhaustive efforts to shed light on the elusive biography/pathography of the
      great Danish philosopher Soren Kierkegaard (1813-55). This 'bicentennial' article
      reviews his main pathographical diagnoses of, respectively, possible manic
      depressive [bipolar] disease, epilepsy, complex partial seizure disorder, Landry
      Guillain-Barre's acute ascending paralysis, acute intermittent porphyria with
      possible psychiatric manifestations, and syphilidophobia. 

PMID- 24573752
TI  - Neopositivism and the DSM psychiatric classification. An epistemological history.
      Part 2: Historical pathways, epistemological developments and present-day needs.
AB  - Little is known about the concrete historical sources for the use of
      neopositivist operational criteria by the DSM-III. This paper suggests that
      distinct sources operated implicitly. The current usefulness of the operational
      approach is questioned. It is shown that: (a) in epistemology, neopositivism has
      been replaced by more adequate accounts; (b) psychologists rejected operational
      definitions because these were unable to define the majority of mental phenomena;
      (c) mental symptoms cannot be directly described as such, because they already
      make part of the psychiatric diagnosis to which they belong. In conclusion,
      diagnosing is based on the hermeneutical co-construction of mental symptoms. The
      failure of the neopositivist programme suggests that it is time to reconcile
      scientific formalization and semiotic activity. 

PMID- 24573751
TI  - Through the lens of the hospital magazine: Downshire and Holywell psychiatric
      hospitals in the 1960s and 1970s.
AB  - An exploration of the pages of two psychiatric hospital magazines, Speedwell from
      Holywell Hospital, Antrim, and The Sketch from Downshire Hospital, Downpatrick,
      reveals the activity-filled lives of patients and staff during the 1960s and
      1970s. This was a time of great change in mental health care. It was also a time
      of political turbulence in Northern Ireland. With large in-patient populations,
      both hospitals had a range of occupational and sporting activities available to
      patients and staff. The magazines formed part of the effort to promote the ethos
      of a therapeutic community. While hospital magazines may be viewed as one aspect
      of an institutional system that allowed people to cut themselves off from the
      wider society, they also provided opportunities for budding writers to express
      their views on life in a hospital from the service-user perspective. As such,
      they offer some valuable insights into the lives of psychiatric patients. 

PMID- 24573753
TI  - The relevance of the early history of probability theory to current risk
      assessment practices in mental health care.
AB  - Probability theory is at the base of modern concepts of risk assessment in mental
      health. The aim of the current paper is to review the key developments in the
      early history of probability theory in order to enrich our understanding of
      current risk assessment practices. 

PMID- 24573754
TI  - Autism in flux: a history of the concept from Leo Kanner to DSM-5.
AB  - In this paper, I argue that a new relation between past and present - a supposed
      historical continuity in the meaning of autism - is created by the histories
      written by the discipline itself. In histories of autism written by 'practitioner
      historians', a sense of scientific progress and an essentialist understanding of
      autism legitimize and reinforce current understandings and research directions in
      the field of autism. Conceptual discontinuities and earlier complexities and
      disputes concerning classifying and delineating autism are usually left out of
      the positivist narrative of autism. In an alternative history of the concept of
      autism, I demonstrate that there have been major shifts in the type of symptoms,
      signs and impairments that were - and are - thought to be essential and specific
      for autism. 

PMID- 24573755
TI  - Richard Arwed Pfeifer - a pioneer of 'medical pedagogy' and an opponent of Paul
      Schroder.
AB  - Richard Arwed Pfeifer (1877-1957) was one of the initiators and foster fathers of
      the renowned child-psychiatric and special needs education workgroup at Leipzig
      University under Paul Schroder (1873-1941) in the 1920s and 1930s. This paper is
      an account of their dispute concerning the interrelations between child and
      adolescent psychiatry and special needs education, as well as their disagreement
      about whether adolescent psychopaths should be admitted to specialized child
      psychiatric wards or elsewhere. Moreover, Pfeifer questioned the practical
      relevance of the separation of constitutional and environmentally-based
      psychopathy and fought eugenic research, which he found incompatible with the
      ethics of his profession as a remedial teacher and child psychiatrist. 

PMID- 24573756
TI  - Spiritist delusions and spiritism in the nosography of French psychiatry (1850
      1950).
AB  - At the turn of the twentieth century there was a wave of delusions which had a
      direct link to spiritism in their form and content. These so-called spiritist or
      mediumistic delusions were the object of detailed study, and clinicians assigned
      them a place in nosography, especially in France. This work of classification was
      carried out as a function of the convictions and paradoxes that these delusions
      aroused; it also made it possible to question the relationship between pathology
      and belief. It is therefore important to emphasize certain ideological views of
      psychiatry on para-normality. We observed both a reductionist discourse
      concerning these domains, and at the same time their utilization in the
      construction of psychiatric knowledge. 

PMID- 24573757
TI  - Forbes Winslow and his Journal: With an introduction by.
AB  - During the 19th century, there were few periodicals dedicated to the inchoate
      discipline of alienism (now called 'psychiatry'). Given the newness of alienism
      and the idiosyncratic structure of the British publishing industry at the time,
      for a private individual to start a new specialized journal was a major
      enterprise. Against all odds, Forbes Winslow managed to publish his journal from
      1848 to 1860, and during this period the scholarly nature of his publication
      could not be matched by the Asylum Journal, the official publication of the
      Association of Medical Officers of Asylums and Hospitals for the Insane. Under
      the title Psychological Medicine, Winslow offered a new view of alienism which he
      clearly conceived as a discipline broader than medicine. He strove to inform his
      readers about the conceptual and practical complexities that then (as now) beset
      and besiege the care of the mentally ill. He taught his readers that to
      understand and manage insanity, knowledge of philosophy and of the human sciences
      was as important as knowledge about the brain. In the 1850s this was a new
      message to impart. 

PMID- 24573761
TI  - Dementia praecox revisited.

PMID- 24573763
TI  - Clear cell renal cell carcinoma: multiphasic MDCT enhancement can predict the
      loss of chromosome 8p.
AB  - PURPOSE: To investigate whether imaging features on multiphasic multidetector
      computed tomography (MDCT) can predict the loss of chromosome 8p in clear cell
      renal cell carcinomas (RCCs), a cytogenetic abnormality associated with a higher
      tumor grade and greater risk of recurrence. METHODS: With IRB approval for this
      HIPAA-compliant retrospective study, we queried our institution's pathology
      database to derive all histologically proven cases of clear cell RCC with
      preoperative multiphasic MDCT with as many as four phases (unenhanced,
      corticomedullary, nephrographic, and excretory) from January 2000 to July 2010.
      Of 170 clear cell RCCs with preoperative multiphasic MDCT, 105 clear cell RCCs,
      representing 98 unique patients, had karyotypes of the resected specimens.
      Lesions were evaluated for magnitude and pattern of enhancement, contour,
      neovascularity, calcifications, and size. RESULTS: The corticomedullary phase
      mean enhancement of clear cell RCCs with a loss of 8p was significantly greater
      than that of clear cell RCCs without a loss of 8p (169.5 vs. 127.2 HU, p =
      0.004). A threshold of 165 HU predicted the loss of 8p in clear cell RCCs with an
      accuracy of 78% (69/88), a specificity of 81% (62/77), and a negative predictive
      value of 94% (62/66). There were no significant differences in the pattern of
      enhancement, contour, neovascularity, calcification, or size between clear cell
      RCCs with a loss of 8p and those without this abnormality. CONCLUSION:
      Enhancement on multiphasic MDCT can predict the loss of 8p in clear cell RCCs and
      can thus provide a non-invasive means of guiding further management, including
      surgery, ablation, watchful waiting, or medical management.

PMID- 24573765
TI  - The impact of parental death on child well-being: evidence from the Indian Ocean
      tsunami.
AB  - Identifying the impact of parental death on the well-being of children is
      complicated because parental death is likely to be correlated with other,
      unobserved factors that affect child well-being. Population-representative
      longitudinal data collected in Aceh, Indonesia, before and after the December
      2004 Indian Ocean tsunami are used to identify the impact of parental deaths on
      the well-being of children aged 9-17 at the time of the tsunami. Exploiting the
      unanticipated nature of parental death resulting from the tsunami in combination
      with measuring well-being of the same children before and after the tsunami,
      models that include child fixed effects are estimated to isolate the causal
      effect of parental death. Comparisons are drawn between children who lost one or
      both parents and children whose parents survived. Shorter-term impacts on school
      attendance and time allocation one year after the tsunami are examined, as well
      as longer-term impacts on education trajectories and marriage. Shorter- and
      longer-term impacts are not the same. Five years after the tsunami, there are
      substantial deleterious impacts of the tsunami on older boys and girls, whereas
      the effects on younger children are more muted. 

PMID- 24573766
TI  - Disseminated cutaneous infection caused by Mycobacterium colombiense.

PMID- 24573768
TI  - Preparation, sedation, and monitoring.

PMID- 24573767
TI  - Quantitative determination of c-myc facilitates the assessment of prognosis of
      OSCC patients.
AB  - Myc genes are a family of proto-oncogenes whose proteins are implicated in the
      regulation of cell proliferation, differentiation and apoptosis, and in
      regulating the activity of genes involved in cell division. The aim of the
      present study was to establish a quantitative description of the expression of c
      myc and evaluate its relationship with other clinical and prognostic factors, as
      well as to establish a multivariate survival prediction model. This is a
      retrospective study of 68 patients diagnosed with oral squamous cell carcinoma
      (OSCC). We constructed a tissue microarray for investigating the expression of c
      myc by immunohistochemistry. Statistical analyses were carried out, and a
      multivariate model that predicts survival was established. The average expression
      of c-myc was 50.32 (SD, 26.05) with a range from 6.60 to 99.48; similar for
      initial and advanced tumor stages. Non-smoking patients had higher levels of c
      myc, showing statistically significant differences (Kruskal-Wallis chi2=5.975;
      p=0.05). We found no statistically significant relationship between the
      quantitative expression of c-myc and any other clinical or pathological
      parameters. For each unit of increase of c-myc, the risk increased by 1.15
      (p<0.001; HR, 1.150; 95% CI, 1062-1245). Further study of this protein, which may
      have a significant diagnostic, prognostic and therapeutic value is warranted. Its
      determination can be valuable when used together with other markers to assess the
      prognosis of OSCC patients. 

PMID- 24573769
TI  - Upper gastrointestinal tumors.

PMID- 24573770
TI  - A novel magnetic countertraction device for endoscopic submucosal dissection
      significantly reduces procedure time and minimizes technical difficulty.
AB  - BACKGROUND AND STUDY AIMS: In endoscopic submucosal dissection (ESD), effective
      countertraction may overcome the current drawbacks of longer procedure times and
      increased technical demands. The objective of this study was to compare the
      efficacy of ESD using a novel magnetic countertraction device with that of the
      traditional technique. METHODS: Each ESD was performed on simulated gastric
      lesions of 30 mm diameter created at five different locations. In total, 10 ESDs
      were performed using this novel device and 10 were performed by the standard
      technique. RESULTS: The magnetic countertraction device allowed directional
      tissue manipulation and exposure of the submucosal space. The total procedure
      time was 605 +/- 303.7 seconds in the countertraction group vs. 1082 +/- 515.9
      seconds in the control group (P = 0.021). CONCLUSIONS: This study demonstrated
      that using a novel magnetic countertraction device during ESD is technically
      feasible and enables the operator to dynamically manipulate countertraction such
      that the submucosal layer is visualized directly. Use of this device
      significantly reduced procedure time compared with conventional ESD techniques.

PMID- 24573771
TI  - EUS-guided hepaticogastrostomy combined with fine-gauge antegrade stenting: a
      pilot study.
AB  - BACKGROUND AND STUDY AIM: To minimize bile leakage and avoid possible death
      because of stent migration in endoscopic ultrasound-guided hepaticogastrostomy
      (EUS-HGS), we have recently combined EUS-HGS with EUS-guided antegrade stenting
      (EUS-AS) of the biliary obstruction using a novel uncovered metallic stent with a
      fine-gauge delivery system. In this pilot study, we evaluated the feasibility and
      adverse events associated with this combination therapy using the novel stent.
      PATIENTS AND METHODS: We performed EUS-guided antegrade stenting and
      hepaticogastrostomy in 12 consecutive patients. RESULTS: The novel EUS-AS stent
      was placed across the ampulla of Vater in 8 patients and above the ampulla in 4.
      Technical and functional success rates were 100 %. In addition, the insertion of
      the first stent was achieved in all patients without dilation of the fistula
      between stomach and intrahepatic bile duct. Although 1 patient experienced mild
      pancreatitis, adverse events such as bile peritonitis or stent dysfunction did
      not occur during follow-up (mean 122 days, range 62 - 210 days). CONCLUSION: This
      method appears to safely and effectively avoid adverse events associated with EUS
      HGS.

PMID- 24573772
TI  - RDLPFC area of the brain encodes sentence polarity: a study using fMRI.
AB  - In this study, we use functional magnetic resonance imaging (fMRI) in combination
      with multivoxel pattern analysis to address the question of how mental activities
      that correspond to sentence polarity (affirmative or negative sentences) are
      encoded in the brain. This approach allows us to investigate the role of
      left/right dorsolateral prefrontal cortex (DLPFC) in predicting the neural
      activity of fMRI associated with sentence polarities. Subjects in the experiment
      were asked to judge the matching of the presented picture with the meaning of
      affirmative and negative sentences. Our results highlight the role of RDLPFC in
      encoding of the related mental activity to sentence polarities such that the
      right hemisphere (RDLPFC) can predict sentence polarity with high accuracy as
      compared to the left hemisphere (LDLPFC), and that the negative sentences are
      decoded with high performance as compared to affirmative sentences from the
      RDLPFC across subjects. In addition, this experiment's results show that negative
      sentences involve more syntactic structure than affirmative sentences. 

PMID- 24573773
TI  - Who wants a free brain scan? Assessing and correcting for recruitment biases in a
      population-based sMRI pilot study.
AB  - Neuroimaging research is usually conducted in volunteers who meet a priori
      selection criteria. Selection/volunteer bias is assumed but cannot be assessed.
      During an ongoing population-based cohort study of 1982 older adults, we asked
      1702 active participants about their interest in undergoing a research brain
      scan. Compared with those not interested, the 915 potentially interested
      individuals were significantly younger, more likely to be male, better educated,
      generally healthier, and more likely to be cognitively intact and dementia-free.
      In 48 of the interested individuals, we conducted a previously reported pilot
      structural magnetic resonance imaging (sMRI) study modelling mild cognitive
      impairment (MCI) vs. normal cognition, and Clinical Dementia Rating (CDR) = 0.5
      vs. CDR = 0, as a function of sMRI atrophy ratings. We now compare these 48
      individuals (1) with all interested participants, to assess selection bias; (2)
      with all who had been asked about their interest, to assess volunteer bias; and
      (3) with the entire study cohort, to assess attrition bias from those who had
      dropped out before the question was asked. Using these data in propensity score
      models, we generated weights which we applied to logistic regression models
      reanalyzing the data from the pilot sMRI study. These weighted models adjusted,
      in turn, for selection bias, interest/volunteer bias, and attrition bias. They
      show fewer regions of interest to be associated with MCI/ CDR than were in the
      original unweighted models. When study participants are drawn from a well
      characterized population, they can be compared with non-participants, and the
      information used to correct study results for potential bias and thus provide
      more generalizable estimates. 

PMID- 24573774
TI  - The use of chemical markers for the identification of farm escapees in feral mink
      populations.
AB  - Variations in the contaminant burden in feral and ranch mink, resulting from
      differences in their diet, may permit the identification of farm escapees.
      However, this is only possible in the case of contaminants that accumulate to
      significantly different levels in the two groups of animals. The main objective
      of this study was to identify chemical markers whose concentrations differ
      between feral and ranch mink, by analyzing the accumulation of 13 chemical
      elements in liver and kidney samples. Total mercury levels were up to 15-fold
      higher in kidney, and up to 7-fold higher in liver of feral mink compared with
      ranch mink. The majority of feral mink samples analyzed for mercury, contained
      concentrations that ranged from 1 to 5 MUg/g in kidney (68 %) and from 1 to 5
      MUg/g in liver (70 %). In comparison, the organs of ranch mink had significantly
      lower levels of mercury: 95 % of kidney samples had concentrations below 1 MUg/g
      and 82 % of liver samples had concentrations below 1 MUg/g. Small geographical
      variations in Hg levels were observed in mink from the four studied feral
      populations. Significant differences in Cu concentrations between ranch and feral
      mink were also detected, with low variation within the two groups. Less
      pronounced differences were recorded for other chemical elements. These data
      suggest that Hg and Cu may be used as chemical markers for the identification of
      first generation mink farm escapees.

PMID- 24573775
TI  - The relationship between the bioactivation and detoxification of diazinon and
      chlorpyrifos, and the inhibition of acetylcholinesterase activity in Chirostoma
      jordani from three lakes with low to high organophosphate pesticides
      contamination.
AB  - In fish, a number of studies have linked acetylcholinesterase (AChE) inhibition
      with exposure to organophosphate pesticides (OPs); however, evidence suggests the
      need to study aspects related to the bioactivation and detoxification of OPs,
      since their neurotoxicity is dependent on these processes. Thus, the study aim
      was to examine the relations between chlorpyrifos (CPF) and diazinon (DZN)
      bioactivation by hepatic CYP450 izoenzymes (CYP 2B6, CYP 2C19, CYP 3A4) and
      detoxification by aryl esterases and oxonases with brain and muscle AChE activity
      in Chirostoma jordani from three lakes with low to high OPs contamination in
      water and sediments. We found two patterns of bioactivation in vitro: (i) in fish
      from a lake with high CPF pollution, the main isoenzymes involved in this process
      were CYP 2C19>CYP 2B6>CYP 3A4, and (ii) in fish captured in a lake with a high
      concentration of DZN, the isoenzymes were CYP 3A4>CYP 2C19>CYP 2B6. Bioactivation
      is shown in this study to be fundamental in brain and muscle AChE inhibition in
      vivo. The rate of bioactivation of CPF was lower than for DZN. CPF bioactivation
      was accompanied by reduced detoxification and higher neurotoxicity, which was
      inversely dependent on the environmental contamination of CPF. Detoxification was
      also inversely correlated with environmental contamination by CPF, and was higher
      with diazoxon than chlorpyrifos-oxon. Oxonases were the most relevant enzymes
      involved in detoxification. The current findings suggest a series of strategies
      between the bioactivation and detoxification of OPs that allowed the survival of
      C. jordani despite of OPs pollution levels. 

PMID- 24573777
TI  - Reviewer's comment concerning "Is NICE guidance for identifying lumbar nerve root
      compression misguided?" (doi:10.1007/s00586-014-3233-y by T. Germon et al.).

PMID- 24573778
TI  - MRI evaluation of lumbar spinal stenosis: is a rapid visual assessment as good as
      area measurement?
AB  - BACKGROUND: Lumbar spinal stenosis (LSS) is commonly assessed on MRI by measuring
      dural sac cross-sectional area (DSCA). A new method, morphological grading A-D,
      has recently been introduced as an alternative method. OBJECTIVE: The aim of this
      study is to compare these two different methods for assessing LSS on MRI and
      study their reliability and intercorrelation. METHODS: On pretreatment MRI of 84
      patients, two experienced radiologists independently classified level L2/L3,
      L3/L4 and L4/L5 as no, relative or significant stenosis using both methods.
      Agreement was analyzed by weighted Kappa. The correlation between the two methods
      was analysed using Spearman correlation, and visualized in a box plot. RESULTS:
      The interobserver agreement (95 % CI) was 0.69 (0.61-0.77) and 0.65 (0.56-0.74),
      respectively. The intraobserver agreements for DSCA were 0.77 (0.60-0.74) and
      0.80 (0.66-0.93). On morphological grading A-D it was 0.78 (0.65-0.92) and 0.81
      (0.68-0.94). The correlation coefficient between the two methods was 0.85 (p <
      0.001). Grades C and D were under the limit value for significant stenosis using
      the DSCA. CONCLUSIONS: The study shows that the inter- and intraobserver
      agreements of DSCA and morphological grading A-D were acceptable and their
      intercorrelation is strong. Both methods may be used in the MRI evaluation of
      LSS.

PMID- 24573776
TI  - Prospects for neuroprotective therapies in prodromal Huntington's disease.
AB  - Huntington's disease (HD) is a prototypical dominantly inherited
      neurodegenerative disorder characterized by progressive cognitive deterioration,
      psychiatric disturbances, and a movement disorder. The genetic cause of the
      illness is a CAG repeat expansion in the huntingtin gene, which leads to a
      polyglutamine expansion in the huntingtin protein. The exact mechanism by which
      mutant huntingtin causes HD is unknown, but it causes abnormalities in gene
      transcription as well as both mitochondrial dysfunction and oxidative damage.
      Because the penetrance of HD is complete with CAG repeats greater than 39,
      patients can be diagnosed well before disease onset with genetic testing.
      Longitudinal studies of HD patients before disease onset have shown that subtle
      cognitive and motor deficits occur as much as 10 years before onset, as do
      reductions in glucose utilization and striatal atrophy. An increase in
      inflammation, as shown by elevated interleukin-6, occurs approximately 15 years
      before onset. Detection of these abnormalities may be useful in defining an
      optimal time for disease intervention to try to slow or halt the degenerative
      process. Although reducing gene expression with small interfering RNA or short
      hairpin RNA is an attractive approach, other approaches targeting energy
      metabolism, inflammation, and oxidative damage may be more easily and rapidly
      moved into the clinic. The recent PREQUEL study of coenzyme Q10 in presymptomatic
      gene carriers showed the feasibility of carrying out clinical trials to slow or
      halt onset of HD. We review both the earliest detectable clinical and laboratory
      manifestations of HD, as well as potential neuroprotective therapies that could
      be utilized in presymptomatic HD.

PMID- 24573781
TI  - Superconducting double perovskite bismuth oxide prepared by a low-temperature
      hydrothermal reaction.
AB  - Perovskite-type structures (ABO3) have received significant attention because of
      their crystallographic aspects and physical properties, but there has been no
      clear evidence of a superconductor with a double-perovskite-type structure, whose
      different elements occupy A and/or B sites in ordered ways. In this report,
      hydrothermal synthesis at 220  degrees C produced a new superconductor with an A
      site-ordered double perovskite structure,
      (Na(0.25)K(0.45))(Ba(1.00))3(Bi(1.00))4O12, with a maximum T(c) of about 27 K.

PMID- 24573779
TI  - Psychometric properties of the eating disorder belief questionnaire.
AB  - OBJECTIVE: The purpose of this investigation was to examine the psychometric
      properties of the eating disorder belief questionnaire (EDBQ). METHOD: The EDBQ
      was administered to clinical patients with bulimia nervosa (n = 44) and
      nonclinical female university students (n = 298). Six types of psychometric
      testing were conducted: internal consistency, test-retest reliability, convergent
      validity, ability to discriminate between clinical and nonclinical groups,
      exploratory factor analysis, and confirmatory factor analysis. RESULTS:
      Psychometric testing generally supported the utility of the EDBQ with good
      internal consistency, 4- to 6-week test-retest reliability, convergent validity,
      and ability to discriminate between groups. The a priori structure of the EDBQ
      was shown to provide a good fit to the observed data. DISCUSSION: The results
      suggest that the EDBQ is a reliable and valid measure that may assist researchers
      and clinicians aiming to assess eating disorder cognitions in populations with
      bulimic symptoms.

PMID- 24573785
TI  - MR imaging of the brachial plexus.
AB  - The characterization of brachial plexus (BP) pathology can be perplexing for the
      radiologist, especially due to varying combination of sensory and motor symptoms
      depending on the extent of disease and the level of disease process. Localization
      can be difficult due to inherently complex anatomy of the BP complicated by a
      variety of benign and malignant disease processes. Infrequently requested imaging
      of the BP, can be a challenge to both the novice and experienced reader. Invasive
      methods of diagnosis, such as biopsy, yield variable results and carry the risk
      of causing permanent sensory and/or motor deficit and may also cause long-term
      neuralgic pain. The purpose of this article is to provide a straightforward
      review of BP pathology as seen by conventional magnetic resonance imaging and to
      illustrate the value of this noninvasive technique in guiding management. 

PMID- 24573788
TI  - Nanocellulose aerogels functionalized by rapid layer-by-layer assembly for high
      charge storage and beyond.

PMID- 24573790
TI  - Solid-phase microextraction: a complementary in vivo sampling method to
      microdialysis.

PMID- 24573791
TI  - Experimental confirmation of low surface energy in LiCoO2 and implications for
      lithium battery electrodes.

PMID- 24573792
TI  - Organocatalytic enantioselective decarboxylative aldol reaction of malonic acid
      half thioesters with aldehydes.

PMID- 24573789
TI  - Recruiting cytotoxic T cells to folate-receptor-positive cancer cells.

PMID- 24573794
TI  - The bidirectional total synthesis of sampsonione P and hyperibone I.

PMID- 24573793
TI  - Nickel-catalyzed cycloaddition of 1,3-dienes with 3-azetidinones and 3
      oxetanones.

PMID- 24573797
TI  - Delicate polydimethylsiloxane hollow fibre membrane interfaces for condensed
      phase membrane introduction mass spectrometry (CP-MIMS).
AB  - RATIONALE: On-line analytical techniques such as condensed phase membrane
      introduction mass spectrometry (CP-MIMS) permit direct and rapid analyte
      measurements in complex samples. Direct, rapid analytical methods are desirable
      because they eliminate potential contamination and/or dilution from sample workup
      steps, facilitate rapid sample screening and allow 'real-time' monitoring
      applications. METHODS: PDMS hollow fibre membrane (HFM) flow cell interfaces (215
      um, 35 um, and 0.5 um thick composite) were coupled with an electrospray
      ionization (ESI) triple quadrupole mass spectrometer. A simultaneous push/pull
      methanol acceptor phase delivery system and membrane mounting via epoxy potting
      ensured that the delicate membranes were not ruptured during construction or
      sample measurements. Both flow cell and direct insertion 'J-Probe' interfaces
      using the 0.5 um thick composite PDMS HFM were utilized for direct naphthenic
      acid measurements. RESULTS: Delicate HFM CP-MIMS interfaces were used for the
      rapid screening and continuous, on-line monitoring of carboxylic acids and
      hydroxylated compounds directly in complex sample matrices under ambient
      conditions at pptr - ppb detection limits. Push/pull acceptor phase (methanol)
      delivery maintained ambient hydrostatic pressures within the HFMs, improving ESI
      stability and analytical sensitivity, especially with stopped acceptor flow
      operation. Signal response times less than 2 min were achieved for thin,
      composite PDMS HFMs at 30 degrees C. The continuous monitoring of naphthenic acid
      degradation was demonstrated. CONCLUSIONS: Delicate PDMS HFM CP-MIMS interfaces
      were developed and used for the direct, on-line detection of low volatility,
      polar analytes in complex aqueous samples. Composite PDMS HFM interfaces yielded
      the best overall analytical performance improvements, and were used to
      demonstrate the direct measurement of naphthenic acids in complex aqueous
      samples.

PMID- 24573796
TI  - Investigation of computer-aided diagnosis system for bone scans: a retrospective
      analysis in 406 patients.
AB  - OBJECTIVE: The aim of this study was to investigate the diagnostic ability of a
      completely automated computer-assisted diagnosis (CAD) system to detect
      metastases in bone scans by two patterns: one was per region, and the other was
      per patient. MATERIALS AND METHODS: This study included 406 patients with
      suspected metastatic bone tumors who underwent whole-body bone scans that were
      analyzed by the automated CAD system. The patients were divided into four groups:
      a group with prostatic cancer (N = 71), breast cancer (N = 109), males with other
      cancers (N = 153), and females with other cancers (N = 73). We investigated the
      bone scan index and artificial neural network (ANN), which are parameters that
      can be used to classify bone scans to determine whether there are metastases. The
      sensitivities, specificities, positive predictive value (PPV), negative
      predictive value (NPV), and accuracies for the four groups were compared.
      Receiver operating characteristic (ROC) analyses of region-based ANN were
      performed to compare the diagnostic performance of the automated CAD system.
      RESULTS: There were no significant differences in the sensitivity, specificity,
      or NPV between the four groups. The PPVs of the group with prostatic cancer (51.0
      %) were significantly higher than those of the other groups (P < 0.01). The
      accuracy of the group with prostatic cancer (81.5 %) was significantly higher
      than that of the group with breast cancer (68.6 %) and the females with other
      cancers (65.9 %) (P < 0.01). For the evaluation of the ROC analysis of region
      based ANN, the highest Az values for the groups with prostatic cancer, breast
      cancer, males with other cancers, and females with other cancers were 0.82 (ANN =
      0.4, 0.5, 0.6, 0.7, and 0.8), 0.83 (ANN = 0.7), 0.81 (ANN = 0.5), and 0.81 (ANN =
      0.6), respectively. CONCLUSION: The special CAD system "BONENAVI" trained with a
      Japanese database appears to have significant potential in assisting physicians
      in their clinical routine. However, an improved CAD system depending on the
      primary lesion of the cancer is required to decrease the proportion of false
      positive findings.

PMID- 24573798
TI  - Rapid analysis of Delta-9-tetrahydrocannabinol in hair using direct analysis in
      real time ambient ionization orbitrap mass spectrometry.
AB  - RATIONALE: Forensic hair analysis methods are laborious, time-consuming and
      provide only a rough retrospective estimate of the time of drug intake. Recently,
      hair imaging methods using matrix-assisted laser desorption/ionization mass
      spectrometry (MALDI-MS) were reported, but these methods require the application
      of MALDI matrix and are performed under vacuum. Direct analysis of entire locks
      of hair without any sample pretreatment and with improved spatial resolution
      would thus address a need. METHODS: Hair samples were attached to stainless steel
      mesh screens and scanned in the X-direction using direct analysis in real time
      (DART) ambient ionization orbitrap MS. The DART gas temperature and the accuracy
      of the probed hair zone were optimized using Delta-9-tetrahydrocannabinol (THC)
      as a model compound. Since external contamination is a major issue in forensic
      hair analysis, sub-samples were measured before and after dichloromethane
      decontamination. RESULTS: The relative intensity of the THC signal in spiked
      blank hair versus that of quinine as the internal standard showed good
      reproducibility (26% RSD) and linearity of the method (R(2)  = 0.991). With the
      DART hair scan THC could be detected in hair samples from different chronic
      cannabis users. The presence of THC was confirmed by quantitative liquid
      chromatography/tandem mass spectrometry. Zones with different THC content could
      be clearly distinguished, indicating that the method might be used for
      retrospective timeline assessments. Detection of THC in decontaminated drug user
      hair showed that the DART hair scan not only probes THC on the surface of hair,
      but penetrates deeply enough to measure incorporated THC. CONCLUSIONS: A new
      approach in forensic hair analysis has been developed by probing complete locks
      of hair using DART-MS. Longitudinal scanning enables detection of incorporated
      compounds and can be used as pre-screening for THC without sample preparation.
      The method could also be adjusted for the analysis of other drugs of abuse.

PMID- 24573799
TI  - Infrared multiple-photon dissociation spectroscopy of deprotonated 6
      hydroxynicotinic acid.
AB  - RATIONALE: Hydroxynicotinic acids (2-, 4-, 5- and 6-hydroxy) are widely used in
      the manufacture of industrial products, and hydroxypyridines are important model
      systems for study of the tautomerization of N-heterocyclic compounds. Here we
      determined the gas-phase structure of deprotonated 6-hydroxynicotinic acid
      (6OHNic). METHODS: Anions were generated by electrospray ionization, and isolated
      and stored in a Fourier transform ion cyclotron resonance mass spectrometer.
      Infrared (action) spectra were collected by monitoring photodissociation yield
      versus photon energy. Experimental spectra were then compared with those
      predicted by density functional theory (DFT) and second-order Moller-Plesset
      (MP2) perturbation theory calculations. RESULTS: For neutral 6OHNic, DFT and MP2
      calculations strongly suggest that the 6-pyridone tautomer is favored when
      solvent effects are included. The lowest energy isomer of deprotonated 6OHNic, in
      the aqueous or gas phase, is predicted to be the 6-pyridone structure
      deprotonated by the carboxylic acid group. CONCLUSIONS: The deprotonated, 6
      pyridone structure is confirmed by comparison of the infrared multiple-photon
      photodissociation (IRMPD) spectrum in the region of 1100-1900 cm(-1) with those
      predicted using DFT and MP2 calculations.

PMID- 24573800
TI  - Laser desorption time-of-flight mass spectrometry of atomic switch memory
      Ge2Sb2Te5 bulk materials and its thin films.
AB  - RATIONALE: Although the structure of atomic switch Ge2Sb2Te5 (GST) thin films is
      well established, the composition of the clusters formed in the plasma plume
      during pulsed-laser deposition (PLD) is not known. Laser Desorption Ionization
      Time-of-Flight Mass Spectrometry (LDI-TOF MS) is an effective method for the
      generation and study of clusters formed by laser ablation of various solids and
      thus for determining their structural fragments. METHODS: LDI of bulk or PLD
      deposited GST thin layers and of various precursors (Ge, Sb, Te, and Ge-Te or Sb
      Te mixtures) using a nitrogen laser (337 nm) was applied while the mass spectra
      were recorded in positive and negative ion modes using a TOF mass spectrometer
      equipped with a reflectron while the stoichiometry of the clusters formed was
      determined via isotopic envelope analysis. RESULTS: The singly negatively or
      positively charged clusters identified from the LDI of GST were Ge, Ge2, GeTe,
      Ge2Te, Ten (n = 1-3), GeTe2, Ge2Te2, GeTe3, SbTe2, Sb2Te, GeSbTe2, Sb3Te and the
      low abundance ternary GeSbTe3, while the LDI of germanium telluride yielded Gem
      Ten (+) clusters (m = 1-3, n = 1-3). Several minor Ge-H clusters were also
      observed for pure germanium and for germanium telluride. Sbn clusters (n = 1-3)
      and the formation of binary TeSb, TeSb2 and TeSb3 clusters were detected when
      Sb2Te3 was examined. CONCLUSIONS: This is the first report that elucidates the
      stoichiometry of Gem Sbn Tep clusters formed in plasma when bulk or nano-layers
      of GST material are ablated. The clusters were found to be fragments of the
      original structure. The results might facilitate the development of PLD
      technology for this memory phase-change material.

PMID- 24573801
TI  - Feasibility assessment of a novel selective peptide derivatization strategy for
      sensitivity enhancement for the liquid chromatography/tandem mass spectrometry
      bioanalysis of protein therapeutics in serum.
AB  - RATIONALE: Sensitivity is one major challenge limiting the application of liquid
      chromatography/tandem mass spectrometry (LC/MS/MS) methods for bioanalysis of
      proteins. A novel selective peptide derivatization (SPD) strategy was proposed to
      improve assay sensitivity. The main concept of the SPD strategy is to selectively
      derivatize surrogate peptides of the target protein in the digests, while not
      derivatizing the abundant background peptides, thereby improving the separation
      of target peptides during sample extraction and chromatography, and increasing
      the sensitivity. Additional benefits may help improve sensitivity include (1)
      increased ionization efficiency; (2) improved fragmentation pattern; and (3)
      increased sample extraction recovery of target peptides. METHODS: Feasibility
      assessment of the SPD strategy was conducted using BMS-986012, a monoclonal
      antibody, as the model protein, and with malondialdehyde (MDA) to selectively
      derivatize the arginine-containing surrogate peptide SLIY in tryptic-digested
      monkey serum samples. RESULTS: The decreased polarity and basicity of the MDA
      derivatized peptide SLIY (MDA-SLIY) helped improve its separation from the
      background peptides during solid-phase extraction (SPE) and chromatography. The
      recovery of MDA-SLIY was 36.1-44.2%, which was ~3-fold higher than the recovery
      of peptide SLIY (11.9-16.1%). There was no significant ion suppression for MDA
      SLIY. Overall, SPD improved the sensitivity ~5-fold. SPD methodology was then
      successfully applied to the development of a sensitive LC/MS/MS assay for BMS
      986012 in monkey serum. CONCLUSIONS: This work demonstrates the feasibility of
      the SPD strategy for sensitivity enhancement. SPD can provide a simple, cost
      efficient, and antibody-free sample preparation approach to improve sensitivity.

PMID- 24573802
TI  - Electrospray ionization collision-induced dissociation tandem mass spectrometry
      of amoxicillin and ampicillin and their degradation products.
AB  - RATIONALE: Detailed analysis of the literature results on the electrospray
      ionization mass spectrometry (ESI-MS) fragmentation of amoxicillin and
      ampicillin, and their comparison with our results, have revealed some incorrect
      suggestions or incomplete interpretations of mass spectra of these compounds.
      Therefore, this paper contains a comprehensive discussion devoted to the ESI
      MS/MS of ampicillin and amoxicillin as well as their degradation products, namely
      products of hydrolysis and methanolysis. METHODS: Electrospray ionization
      collision-induced dissociation tandem mass (ESI-CID-MS/MS) spectra and accurate
      mass measurements were made on a quadrupole time-of-flight (Q-tof) mass
      spectrometer. Hydrolysis of the antibiotics was performed by heating, for a few
      hours, their aqueous solutions adjusted to pH 10. Methanolysis of the antibiotics
      was performed by heating their methanol solutions for a few minutes.
      Additionally, mass spectra of isotope-labeled compounds were also obtained.
      RESULTS: A number of fragment ions, previously wrongly interpreted or not
      interpreted, have been rationalized. For example, formation of an abundant
      fragment at m/z 208 originating from the protonated amoxicillin molecule (ion
      [Amox + H](+)) was previously rationalized as a result of breaking of two bonds
      of the beta-lactam ring. We found that this fragment ion had to be formed by the
      loss of ammonia and breaking of three bonds of the bicyclic system. CONCLUSIONS:
      The discussion presented enables a better understanding of the MS decompositions
      of amoxicillin and ampicillin as well as their degradation products. MS
      decomposition is used for the determinations of these compounds, when the so
      called multiple-reaction monitoring is applied during liquid chromatography
      (LC)/ESI-MS analysis. Thus, better understanding of MS decompositions of the
      above compounds seems to be important.

PMID- 24573803
TI  - A systematic investigation of the fragmentation pattern of two furanoheliangolide
      C-8 stereoisomers using electrospray ionization mass spectrometry.
AB  - RATIONALE: Budlein A is a sesquiterpene lactone (STL) with some reported
      biological activities. Pre-clinical studies to identify in vivo metabolites often
      employ hyphenated techniques such as liquid chromatography/tandem mass
      spectrometry (LC/MS/MS). It is also possible to use the fragmentation pattern
      obtained by Collision-Induced Dissociation (CID) and Higher Energy Collision
      Induced Dissociation (HCD) to distinguish between the stereoisomers budlein A and
      centratherin. METHODS: The experiments were carried out in the positive mode
      using four different spectrometers with an electrospray ionization (ESI) source:
      (a) Waters ACQUITY((r)) TQD triple quadrupole mass spectrometer (QqQ), (b) AB
      Sciex API 4000 QTrap((r)) (QqQ), (c) Bruker Daltonics micrOTOFTM-Q II (time-of
      flight, QTOF), and (d) Thermo Scientific LTQ Orbitrap XL hybrid FTMS (Fourier
      transform mass spectrometer). Computational chemistry studies helped to identify
      the protonation sites. The B3LYP/6-31G(d) model furnished the equilibrium
      geometries and energies. RESULTS: The stereochemistry (alpha- or beta
      orientation) of the centratherin and budlein A side-chain esters influences the
      fragmentation pattern recorded on QqQ, QTOF, and Orbitrap-HCD. On QqQ,
      centratherin releases the side chain, to generate the m/z 275 fragment ion,
      whereas budlein A gives the m/z 83 fragment ion. On QTOF and Orbitrap-HCD, only
      budlein A affords the m/z 293 and 83 fragment ions, respectively. CONCLUSIONS:
      The data suggest that proton migration governs the fragmentation pathways under
      alpha- or beta-orientation. The difference in the QqQ, QTOF, and Orbitrap-HCD
      spectral profiles of each isomer can help to distinguish between centratherin and
      budlein A using MS/MS, which becomes an alternative to nuclear magnetic resonance
      (NMR) analysis.

PMID- 24573804
TI  - Analysis of amphetamine-type substances and piperazine analogues using desorption
      electrospray ionisation mass spectrometry.
AB  - RATIONALE: Although amphetamine-type substances (ATS) have been investigated
      extensively in recent years, scarce data is available on screening tests for
      piperazine analogues. The need for a universal technique capable of detecting an
      extensive range of drug compounds becomes increasingly important with the
      continued emergence of novel drug analogues. METHODS: Desorption electrospray
      ionisation mass spectrometry (DESI-MS) is a technique that allows examination of
      compounds in drug materials directly from ambient surfaces. In this study, DESI
      MS was utilised in the analysis of ATS including amphetamine (AP),
      methylamphetamine (MA), 3,4-methylenedioxymethylamphetamine (MDMA), N,N
      dimethylamphetamine (DMA), 4-methoxyamphetamine (PMA) and 4
      methoxymethylamphetamine (PMMA), and piperazine analogues including 1
      benzylpiperazine (BZP), 1-[3-(trifluoromethyl)phenyl]piperazine (TFMPP), 1-(3
      chlorophenyl)piperazine (mCPP) and 1-(4-methoxyphenyl)piperazine (MeOPP). Semi
      porous polytetrafluoroethylene (PTFE or Teflon) sheets welled with a 3 mm hole
      punch were used to contain the 2 MUL liquid sample (spot size 7 mm(2) ). RESULTS:
      The limits of detection (LODs) of these compounds using DESI-MS were determined
      to be in the range 0.02-2.80 ug/mm(2) . The intra-day and inter-day precision of
      the technique were <25% and <33%, respectively. DESI-MS was successful in
      determining the compound of interest and reaction by-products and impurities in
      the samples tested (such as 1,4-dibenzylpiperazine in BZP samples) with the
      exception of those present in trace amounts. The effects of common adulterants on
      the detectability of MA were evaluated. The addition of magnesium stearate to MA
      significantly enhanced the signal response. CONCLUSIONS: This work has
      demonstrated the applicability of DESI-MS in the screening and profiling of MDMA,
      PMMA, BZP, TFMPP, mCPP, MeOPP as well as other complex mixtures.

PMID- 24573805
TI  - Proteomics study of N-acetylcysteine response in H1N1-infected cells by using
      mass spectrometry.
AB  - RATIONALE: The pathology of A/Puerto Rico/8/1934 (H1N1) infection associated with
      the interaction of virus and its host cells is not clear. N-Acetylcysteine (NAC)
      is an antioxidant as well as a premier antitoxin and immune support substance. A
      high dose of NAC was recently reported for a therapy of H1N1 (2009) influenza
      pneumonia. METHODS: NAC was used as a small-molecule organic probe to investigate
      the protein expression of human lung carcinoma cell line (A549) infected by
      influenza virus A/Puerto Rico/8/1934 (H1N1). Differential proteins were
      identified from MALDI-TOF MS and Q-TOF MS/MS analyses. RESULTS: The obtained
      results showed that NAC kept cells away from apoptosis. Virus-infected cells were
      arrested in G0/G1 phase. The lowest cell population of G0/G1 phase was detected
      when the cells were treated by 10 mM NAC for one day. Application of MS-based
      proteomics allowed the identification of the differential proteins. Software
      analysis showed that four proteins had close relationship. CONCLUSIONS: The
      results indicated that NAC as a small-molecule probe might effect the protein
      expression of A549 cells infected by the H1N1 virus.

PMID- 24573806
TI  - A rapid and high-precision method for sulfur isotope delta(34)S determination
      with a multiple-collector inductively coupled plasma mass spectrometer: matrix
      effect correction and applications for water samples without chemical
      purification.
AB  - RATIONALE: Previous studies have indicated that prior chemical purification of
      samples, although complex and time-consuming, is essential in obtaining precise
      and accurate results for sulfur isotope ratios using multiple-collector
      inductively coupled plasma mass spectrometry (MC-ICP-MS). In this study, we
      introduce a new, rapid and precise MC-ICP-MS method for sulfur isotope
      determination from water samples without chemical purification. METHODS: The
      analytical work was performed on an MC-ICP-MS instrument with medium mass
      resolution (m/Deltam ~ 3000). Standard-sample bracketing (SSB) was used to
      correct samples throughout the analytical sessions. Reference materials included
      an Alfa-S (ammonium sulfate) standard solution, ammonium sulfate provided by the
      lab of the authors and fresh seawater from the South China Sea. A range of matrix
      matched Alfa-S standard solutions and ammonium sulfate solutions was used to
      investigate the matrix (salinity) effect (matrix was added in the form of NaCl).
      A seawater sample was used to confirm the reliability of the method. RESULTS:
      Using matrix-matched (salinity-matched) Alfa-S as the working standard, the
      measured delta(34)S value of AS (-6.73 +/- 0.090/00) was consistent with the
      reference value (-6.78 +/- 0.070/00) within the uncertainty, suggesting that this
      method could be recommended for the measurement of water samples without prior
      chemical purification. The delta(34)S value determination for the unpurified
      seawater also yielded excellent results (21.03 +/- 0.180/00) that are consistent
      with the reference value (20.990/00), thus confirming the feasibility of the
      technique. CONCLUSIONS: The data and the results indicate that it is feasible to
      use MC-ICP-MS and matrix-matched working standards to measure the sulfur isotopic
      compositions of water samples directly without chemical purification. In
      comparison with the existing MC-ICP-MS techniques, the new method is better for
      directly measuring delta(34)S values in water samples with complex matrices;
      therefore, it can significantly accelerate analytical turnover.

PMID- 24573807
TI  - Multi-stage tandem mass spectrometric analysis of novel beta-cyclodextrin
      substituted and novel bis-pyridinium gemini surfactants designed as nanomedical
      drug delivery agents.
AB  - RATIONALE: This study aimed at evaluating the collision-induced dissociation
      tandem mass spectrometric (CID-MS/MS) fragmentation patterns of novel beta
      cyclodextrin-substituted- and bis-pyridinium gemini surfactants currently being
      explored as nanomaterial drug delivery agents. In the beta-cyclodextrin
      substituted gemini surfactants, a beta-cyclodextrin ring is grafted onto an N,N
      bis(dimethylalkyl)-alpha,omega-aminoalkane-diammonium moiety using variable
      succinyl linkers. In contrast, the bis-pyridinium gemini surfactants are based on
      a 1,1'-(1,1'-(ethane-1,2-diylbis(sulfanediyl))bis(alkane-2,1-diyl))dipyridinium
      template, defined by two symmetrical N-alkylpyridinium parts connected through a
      fixed ethane dithiol spacer. METHODS: Detection of the precursor ion [M](2+)
      species of the synthesized compounds and the determination of mass accuracies
      were conducted using a QqTOF-MS instrument. A multi-stage tandem MS analysis of
      the detected [M](2+) species was conducted using the QqQ-LIT-MS instrument. Both
      instruments were equipped with an electrospray ionization (ESI) source. RESULTS:
      Abundant precursor ion [M](2+) species were detected for all compounds at sub-1
      ppm mass accuracies. The beta-cyclodextrin-substituted compounds, fragmented via
      two main pathways: Pathway 1: the loss of one head-tail region produces a [M
      (N(Me)2-R)](2+) ion, from which sugar moieties (Glc) are sequentially cleaved;
      Pathway 2: both head-tail regions are lost to give [M-2(N(Me)2-R)](+), followed
      by consecutive loss of Glc units. Alternatively, the cleavage of the Glc units
      could also have occurred simultaneously. Nevertheless, the fragmentation evolved
      around the quaternary ammonium cations, with characteristic cleavage of Glc
      moieties. For the bis-pyridinium gemini compounds, they either lost neutral
      pyridine(s) to give doubly charged ions (Pathway A) or formed complementary
      pyridinium alongside other singly charged ions (Pathway B). Similar to beta
      cyclodextrin-substituted compounds, the fragmentation was centered on the
      pyridinium functional groups. CONCLUSIONS: The MS(n) analyses of these novel
      gemini surfactants, reported here for the first time, revealed diagnostic ions
      for each compound, with a universal fragmentation pattern for each compound
      series. The diagnostic ions will be employed within liquid chromatography
      (LC)/MS/MS methods for screening, identification, and quantification of these
      compounds within biological samples.

PMID- 24573808
TI  - Determination of selected reaction monitoring peptide transitions via multiplexed
      product-ion scan modes.
AB  - RATIONALE: Although in silico prediction of selected reaction monitoring (SRM)
      peptide transitions is the most commonly used approach in quantitative
      proteomics, systematically detectable peptide transitions selected from actual
      experimental data are desirable. Here, we demonstrated the use of two triple
      quadrupole mass spectrometry (QqQ-MS) operation modes to identify reliable SRM
      peptide transitions of target peptides selected from a shotgun proteomic linear
      ion-trap mass spectrometry (LIT-MS) profiling dataset. METHODS: Transition ions
      (Q1 and Q3 ions) of target peptides were selected from the LIT MS/MS spectra. We
      performed multiplexed SRM blindly for the selected transition ions of target
      peptides using QqQ-MS and selected peptide transitions for which the
      chromatographically aligned and correlated ion intensities to the corresponding
      fragment ions appeared in the LIT MS/MS spectra. The identities of the peptides
      were further confirmed by MS/MS spectra acquired via SRM-triggered MS/MS on QqQ
      MS. RESULTS: Despite the different MS platforms, we observed similar MS/MS
      patterns and relative ion abundance using both LIT-MS and QqQ-MS. Therefore, we
      were able to determine peptide transitions based on matching the chromatographic
      peak areas of all the selected Q3 ions of target peptides by the order of the
      corresponding ion intensities in the LIT MS/MS spectra. This approach
      demonstrated an efficient method to determine SRM peptide transitions,
      particularly when the target proteins are in low abundance and are therefore not
      easily detected by the QqQ full MS/MS scan mode. We employed this approach to
      determine the SRM peptide transitions of mitochondrial oxidative phosphorylation
      (OXPHOS) proteins involved in mitochondrial ATP synthesis. CONCLUSIONS: The
      multiplexed product-ion scan mode using QqQ-MS generates systematically
      detectable peptide transitions in a single liquid chromatography/MS run, in which
      we were able to identify SRM peptides that represent known target proteins in
      complex biological samples. The method presented here is easy to implement and
      has high-throughput capabilities as a result of the short analysis time. It is
      therefore well suited for the design of optimal SRM experiments.

PMID- 24573809
TI  - Isotope-dilution mass spectrometric quantification of the prodrug
      lisdexamfetamine in human urine in doping control analysis.
AB  - RATIONALE: Therapeutic approaches concerning attention-deficit hyperactivity
      disorder (ADHD) commonly include the administration of drugs amplifying cerebral
      dopamine and norepinephrine signals. Among these, compounds belonging to the
      Prohibited List as established by the World Anti-Doping Agency (WADA) are present
      such as amfetamine or methylphenidate, and abuse of these can result in sanctions
      for athletes. The recently approved therapeutic lisdexamfetamine represents a
      slow-release prodrug of amfetamine for ADHD treatment. In order to support doping
      control laboratories in differentiating the abuse of amfetamine from a
      therapeutic administration of lisdexamfetamine, the determination of the prodrug
      from urine is desirable. Since approximately 2% of lisdexamfetamine are
      eliminated intact into urine, a liquid chromatography/high-resolution/high
      accuracy mass spectrometric method was developed, allowing the target analyte and
      one of its metabolites (4-hydroxyamfetamine sulfate) to be accurately quantified.
      METHODS: Urine samples were fortified with fourfold deuterated lisdexamfetamine
      and analyzed directly using ultrahigh-performance liquid chromatography (UHPLC)
      interfaced via electrospray ionization to a second-generation quadrupole-orbitrap
      mass spectrometer. The assay was characterized concerning specificity, limits of
      quantification (0.15-5 ng/mL), intraday and interday imprecision (4-22%),
      accuracy (90-120%), linearity, and ion suppression/enhancement effects. A
      patient's urine samples were analyzed to provide proof-of-principle data
      demonstrating that the intact prodrug lisdexamfetamine is detectable in urine up
      to 11 h post-administration at concentrations up to 80 ng/mL. Moreover,
      amfetamine and sulfoconjugated 4-hydroxyamfetamine were measured, yielding up to
      1146 and 56 ng/mL, respectively. CONCLUSIONS: Considering the observed comparably
      low urinary concentrations of lisdexamfetamine and 4-hydroxyamfetamine sulfate,
      the preferred minimally labor-intense sample preparation, and the necessity of
      fast and robust result generation, the employed instrumental setup proved fit-for
      purpose in sports drug testing.

PMID- 24573810
TI  - Dual track time-of-flight mass spectrometry for peptide quantification with
      matrix-assisted laser desorption/ionization.
AB  - RATIONALE: Previously, we reported a method (Anal. Chem. 2012, 84, 10332) for
      peptide quantification based on matrix-assisted laser desorption/ionization
      (MALDI) time-of-flight (TOF) mass spectrometry (MS). In the method, the peptide
      to-matrix ion abundance ratio was utilized. Implementation of the method with a
      commercial MALDI-TOF can be somewhat inconvenient because matrix-derived ions are
      routinely deflected away to avoid detector saturation. A solution for this
      inconvenience is required. METHODS: We installed a detector to acquire the TOF
      spectrum of the ions thrown away to avoid detector saturation. By sending the
      matrix- and peptide-derived ions along two different tracks and detecting them
      with different detectors, the inconvenience mentioned above could be avoided.
      RESULTS: Excellent linearity of the calibration curves obtained by the dual track
      TOF spectrometry is demonstrated. The method also allows for the acquisition of
      the tandem mass spectrum of a selected peptide, which can be useful for its
      identification. CONCLUSIONS: We devised the dual track MALDI-TOF MS method to
      avoid detector saturation and demonstrated that the quantification and
      identification of peptides can be performed simultaneously.

PMID- 24573812
TI  - High-temperature mass spectrometric study and modeling of thermodynamic
      properties of binary glass-forming systems containing Bi2O3.
AB  - RATIONALE: Binary glass-forming systems containing bismuth(III) oxide, especially
      the Bi2O3-SiO2 system, are of great importance in modern materials science:
      preparation of thin films, fiber optics, potential solar converters, and
      radiation shields in nuclear physics. Information on vaporization processes and
      thermodynamic properties obtained in the present study and the results of
      modeling of this system will be useful for optimization of the synthesis and
      applications of Bi2O3-containing materials at high temperatures. METHODS: High
      temperature Knudsen effusion mass spectrometry was used to study the vaporization
      processes and to determine the partial pressures of components of the Bi2O3-SiO2
      system. Measurements were performed with a MS-1301 mass spectrometer.
      Vaporization was carried out using two iridium-plated molybdenum effusion cells
      containing the sample under study and pure bismuth(III) oxide (reference
      substance). Modeling of the thermodynamic properties and structure of glasses and
      melts in the Bi2O3-SiO2 and Bi2O3-B2O3 systems was performed using a modified
      approach based on the generalized lattice theory of associated solutions (GLTAS).
      RESULTS: At a temperature of 1000 K, Bi and O2 were found to be the main vapor
      species over the samples studied. The Bi2O3 activity as a function of composition
      of the Bi2O3-SiO2 system was obtained from the measured partial pressures of the
      vapor species. The thermodynamic properties of mixing from oxides in this system
      were calculated. The advantages of GLTAS for modeling of glasses and melts in the
      binary systems containing Bi2O3 were demonstrated. CONCLUSIONS: The thermodynamic
      functions of mixing in glasses and melts of the Bi2O3-SiO2 system determined at
      1000 K in the present study, as well as in the Bi2O3-B2O3 system, demonstrated
      negative deviations from ideality. Modeling of the obtained experimental data
      using GLTAS allowed a correlation to be found between the thermodynamic
      properties and the relative number of bonds of various types formed in the
      glasses and melts of these systems.

PMID- 24573811
TI  - Probing bunyavirus N protein oligomerisation using mass spectrometry.
AB  - RATIONALE: Bunyaviruses have become a major threat to both humans and livestock
      in Europe and the Americas. The nucleocapsid (N) protein of these viruses is key
      to the replication cycle and knowledge of the N oligomerisation state is central
      to understanding the viral lifecycle and for development of therapeutic
      strategies. METHODS: Bunyamwera virus and Schmallenberg virus N proteins (BUNV-N
      and SBV-N) were expressed recombinantly in E. coli as hexahistidine-SUMO-tagged
      fusions, and the tag removed subsequently. Noncovalent nano-electrospray
      ionisation mass spectrometry was conducted in the presence and absence of short
      RNA oligonucleotides. Instrumental conditions were optimised for the transmission
      of intact protein complexes into the gas phase. The resulting protein-protein and
      protein-RNA complexes were identified and their stoichiometries verified by their
      mass. Collision-induced dissociation tandem mass spectrometry was used in cases
      of ambiguity. RESULTS: Both BUNV-N and SBV-N proteins reassembled into N-RNA
      complexes in the presence of RNA; however, SBV-N formed a wider range of
      complexes with varying oligomeric states. The N:RNA oligomers observed were
      consistent with a model of assembly via stepwise addition of N proteins.
      Furthermore, upon mixing the two proteins in the presence of RNA no heteromeric
      complexes were observed, thus revealing insights into the specificity of
      oligomerisation. CONCLUSIONS: Noncovalent mass spectrometry has provided the
      first detailed analysis of the co-populated oligomeric species formed by these
      important viral proteins and revealed insights into their assembly pathways.
      Using this technique has also enabled comparisons to be made between the two N
      proteins.

PMID- 24573813
TI  - Evaluation and optimization of high-performance liquid chromatography coupled
      with high-resolution mass spectrometry for phospholipid quantitation.
AB  - RATIONALE: High-performance liquid chromatography coupled with high-resolution
      mass spectrometry (HPLC/HRMS) provides an attractive alternative to the
      traditional triple quadrupole mass spectrometry selected reaction monitoring
      (SRM) methodology in the field of quantitation. METHODS: An LTQ Orbitrap Velos
      mass spectrometer coupled with a Shimadzu UHPLC system was used. A mass
      extraction window (MEW) was defined to mathematically correlate with mass
      resolving power (MRP). Five MRP measurement conditions at 7500, 15,000, 30,000,
      60,000, and 100,000, and five MEW widths at 10%, 20%, 50%, and 100% of +/
      1000000/MRP, and were utilized as the experimental conditions. Comparison of
      profile and centroid algorithms was evaluated as well. RESULTS: Selection of pH
      8.5 buffer, C4 column, 20% IPA, and 10 ppm H3 PO4 , minimized hydrophobic and
      silanol interactions to enhance separation. Narrowing the MEW minimized
      background noise, while over-narrowing the MEW gave signal loss due to mass
      accuracy deviation. The mass accuracy deviation was larger for lower MRP
      measurements especially with centriod data, and hence a profile algorithm was
      recommended. The post-ionization signal suppression was observed with low MRP and
      was further confirmed with the analysis of multi-level linearity. CONCLUSIONS: It
      was found that the HPLC/HRMS method with conditions of 20% +/-1000000/MRP as MEW,
      30,000 or 60,000 MRP, and profile algorithm, provide optimum results for
      quantitation of seven model phospholipids.

PMID- 24573814
TI  - Fragmentation study of noscapine derivatives under electrospray conditions.
AB  - RATIONALE: Noscapine is a biologically active molecule with anticancer activity
      among other things. Therefore, from an analytical point of view, knowledge of the
      mass spectrometric properties of noscapine and its derivatives is essential. The
      goal of the present study is to describe the collision-induced dissociation
      behavior of noscapine and its seven derivatives ionized by protons and lithium
      and sodium ions. METHODS: Protonated noscapines were produced using electrospray
      ionization (ESI) mass spectrometry (MS). For the tandem mass spectrometry (MS/MS)
      experiments nitrogen was used as the collision gas and the collision energies
      were varied in the range of 1-53 eV (in the laboratory frame). RESULTS: The ESI
      MS/MS measurements showed that the MS/MS spectra of the protonated noscapines
      were more informative than the lithiated and sodiated ones. Based on the MS/MS
      studies, the main fragmentation channels of the protonated noscapines were found
      to be the loss of water and the loss of a meconine moiety from the precursor ion;
      furthermore, methyl transfer was also observed in the MS/MS spectra. CONCLUSIONS:
      The MS/MS study of the protonated noscapines gives more structural information
      than that of lithiated and sodiated noscapines. However, the most important
      fragmentation channel, which leads to the formation of the most intensive product
      ion in the MS/MS spectra, is independent of the ionization agent.

PMID- 24573815
TI  - Facile Smiles-type rearrangement in radical cations of N-acyl arylsulfonamides
      and analogs.
AB  - RATIONALE: N-Alkylation of sulfonylbenzamides was reported recently to cause a
      dramatic and surprising change in electron ionization mass spectrometry (EIMS),
      leading to a closed-shell base peak. Only an incomplete, speculative mechanism
      was available at that time. The fragmentation mechanism is determined in the
      present work and set in the context of related compounds. METHODS: Candidate
      reaction mechanisms were evaluated theoretically using modest density-functional
      calculations. The fragmentation mechanism with the lowest barriers was identified
      and one of its implications tested successfully by experimental (18) O-isotopic
      substitution. RESULTS: The amide oxygen atom attacks the arylsulfonyl group at
      the ipso position (Smiles-type rearrangement), displacing a molecule of SO2 . The
      resulting carboximidate radical cation has a weak C-O bond that breaks easily.
      The incipient aryloxyl radical abstracts a proton from the amide nitrogen to form
      the dominant product ion, but if the molecule is N-alkylated this cannot occur.
      Instead, the neutral aryloxyl radical is lost and a closed-shell, N-alkyl
      nitrilium ion is the major product. CONCLUSIONS: The Smiles-type ion
      fragmentation mechanism is facile for the title compounds, despite the necessity
      for carbonyl oxygen to serve as a nucleophile. This rearrangement probably occurs
      in many of the mass spectra reported for structurally similar compounds, in which
      the nucleophile may be a thione, arylthio, imine, methylene, or methine moiety.

PMID- 24573816
TI  - Accessibilities of N-terminal myristoyl chain and cysteines in guanylyl cyclase
      activating protein-2 (GCAP-2) studied by covalent labeling and mass spectrometry.

PMID- 24573817
TI  - Investigation of noncovalent interactions of aconitine with duplex, triplex and G
      quadruplex DNA by electrospray ionization mass spectrometry.

PMID- 24573818
TI  - Virtual special issue of the 3rd Joint European Stable Isotope Users group
      Meeting (JESIUM) 2012, held in Leipzig, Germany.

PMID- 24573821
TI  - Using secondary analysis of qualitative data of patient experiences of health
      care to inform health services research and policy.
AB  - Qualitative research is recognized as an important method for including patients'
      voices and experiences in health services research and policy-making, yet the
      considerable potential to analyse existing qualitative data to inform health
      policy and practice has been little realized. This failure may partly be
      explained by: a lack of awareness amongst health policy makers of the increasing
      wealth of qualitative data available; and around 15 years of internal debates
      among qualitative researchers on the strengths, limitations and validity of re
      use of qualitative data. Whilst acknowledging the challenges of qualitative
      secondary data analysis, we argue that there is a growing imperative to be
      pragmatic and to undertake analysis of existing qualitative data collections
      where they have the potential to contribute to health policy formulation. Time
      pressures are inherent in the policy-making process and in many circumstances it
      is not possible to seek funding, conduct and analyse new qualitative studies of
      patients' experiences in time to inform a specific policy. The danger then is
      that the patient voice, and the experiences of relatives and carers, is either
      excluded or included in a way that is easily dismissed as 'unrepresentative'. We
      argue that secondary analysis of qualitative data collections may sometimes be an
      effective means to enable patient experiences to inform policy decision-making.

PMID- 24573820
TI  - A Th2 cytokine interleukin-31 signature in a case of sporadic lichen amyloidosis.

PMID- 24573822
TI  - [Always a topic: the distal radius fracture].

PMID- 24573819
TI  - Opioid use prior to total hip arthroplasty leads to worse clinical outcomes.
AB  - PURPOSE: The purpose of this study was to compare the clinical outcomes of
      patients undergoing total hip arthroplasty (THA) who had been using narcotic
      medications prior to surgery to those who had not used them. METHODS: Fifty-four
      patients (62 hips) who had required opioid analgesia for hip pain in the three
      months prior to THA were compared to a matched group of opioid-naive patients.
      Narcotic consumption was converted to a standardized morphine equivalent dose and
      compared between both groups of patients during their hospital stay, after six
      weeks, and at final follow-up. Other outcome measures included clinical outcome
      scores and the proportion of patients remaining on narcotic pain medication at
      final follow-up. RESULTS: The narcotic group required significantly higher total
      daily opioid doses as inpatients had a longer hospital stay and a higher
      proportion of patients who remained on opioids at six weeks and at final follow
      up. Of the patients who were taking opioids pre-operatively, 81 % were able to
      wean off opioids at final follow-up. At a mean post-operative follow-up of 58
      months (range, 24-258 months), Harris hip scores were lower in the narcotic
      group, with a mean of 84 compared to 91 points in the matching group. However, in
      both cohorts, there were significant improvements in Harris hip scores compared
      to pre-operative outcomes. CONCLUSIONS: Patients who use narcotics prior to total
      hip arthroplasty may be more likely to suffer from opioid-induced hyperalgesia
      after surgery and have worse clinical outcomes. When possible, efforts should be
      made to use other modes of analgesia or wean patients from their use prior to
      total hip arthroplasty.

PMID- 24573823
TI  - [Radiological evaluation of k-wire osteosynthesis, in comparison to fixed-angle
      plate osteosynthesis, in patients aged 80 years or more with distal radius
      fractures].
AB  - BACKGROUND: This study evaluates the short-term radiological outcome of K-wire
      osteosynthesis (KWO) in comparison to the fixed-angle-plate osteosynthesis (ORIF)
      on distal radius fractures in elderly patients (aged 80 years or more) with
      osteoporotic bones. PATIENTS AND METHODS: This study retrospectivly compares the
      postoperative X-rays of distal radius fractures (obtained between the years of
      1998-2009) of patients aged 80 years and above treated with KWO (228 fractures,
      mean age 85 years), with the results of patients who were treated with fixed
      angle plate ORIF (120 fractures, mean age 84 years). Within the KWO results, we
      also further compared the radiological results of a static and a dynamic
      (Kapandji) KWO technique. Only patients with a postoperative, anatomic reduction,
      and those who were radiologically followed up in a period of 2 months and above
      were included. The radiological criteria included the palmar and radial
      inclination as well as the radial shortening. RESULTS: With KWO performed in a
      static technique, 24% of the postoperative results showed no reduction loss. The
      use of the dynamic Kapandji technique KWO, improved the positive results to 63%.
      However, almost a third of the fractures (30%) treated with KWO, had shifted back
      to their preoperative positions, or worsened overall. The fixed angle plate
      (ORIF) was able to maintain 76% of all fractures in their postoperative
      positions. Merely 1.7% of the ORIF group sustained a complete reduction loss. The
      fixed-angle plate osteosynthesis shows a significant decrease of cases in which a
      complete repositioning loss is experienced. CONCLUSION: Although the importance
      of anatomic reconstruction of distal radius fractures is often debated in cases
      involving elderly patients, it is our considered opinion that, should an
      operative solution be chosen, one should consider the fixed-angle-plate
      osteosynthesis as the preferred operation method to prevent loss of reduction.

PMID- 24573824
TI  - A comparison of outcomes after K-wire fixation of distal radius fractures with
      and without associated ulnar styloid fracture.
AB  - PURPOSE: A prospective study was carried out to compare outcomes after K-wire
      fixation of distal radius fractures without and with associated ulnar styloid
      fracture, but without fixation of the styloid fracture. PATIENTS AND METHODS: 70
      patients, 60 women (86%) and 10 men (14%) with a mean age of 63 years were
      enrolled. 35 patients had an isolated fracture of the distal radius and 35 had an
      associated fracture of the ulnar styloid. All patients underwent percutaneous,
      "augmented" K-wire fixation of the distal radius fracture; the ulnar styloid
      fracture was left untreated. The patients were followed-up at 3 and 6 months. The
      stability of the distal radioulnar joint and the DASH scores were considered to
      be primary outcome measures. RESULTS: Instability of the distal radioulnar joint
      was diagnosed in 2 patients with ulnar styloid fracture. No significant and
      clinically meaningful differences were found between the groups in clinical
      (pain, wrist mobility, grip strength, DASH score) and radiological outcomes. The
      rate of non-union of the ulnar styloid was 77% at final assessment. CONCLUSION:
      An unrepaired ulnar styloid fracture does not affect the outcome of a distal
      radius fracture which is fixed by the "augmented" K-wire method.

PMID- 24573825
TI  - [Osteoconductive behaviour of beta-tricalcium phosphate ceramics in osteoporotic,
      metaphyseal bone defects of the distal radius].
AB  - BACKGROUND: Surgical treatment of osteoporotic distal radius fractures with
      locking plates does not completely prevent loss of reduction. Additional bone
      deficit stabilisation with the use of bone substitute materials is receiving
      increased attention. Most knowledge on the in vivo behavior of bone substitutes
      originates from a small number of animal models after its implantation in young,
      good vascularized bone. PURPOSE: This paper investigates the osteoconductivity,
      resorption and biocompatibility of beta-tricalcium phosphate as a temporary bone
      replacement in osteoporotic type distal radius fractures. PATIENTS AND METHODS:
      15 bone samples taken from the augmented area of the distal radius of elderly
      people during metal removal were examined. RESULTS: The material was found to be
      osteoconductive, good degradable, and biocompatible. Degrading process and
      remodelling to woven bone seem to require more time than in available comparative
      bioassays. CONCLUSIONS: The material is suitable for temporary replacement of
      lost, distal radius bone from the histological point of view.

PMID- 24573826
TI  - Galeazzi fractures: our modified classification and treatment regimen.
AB  - While diaphyseal fractures of the forearm are a common orthopedic injury,
      Galeazzi fractures are difficult to treat. The current knowledge on
      pathobiomechanics and modified therapeutic decisions implicate the need to devise
      an updated classification and treatment regimen of Galeazzi fractures. We
      challenge the concept that isolated fractures of the radius should be considered
      as a Galeazzi fractures as long as stability of the distal radioulnar joint is
      not proven. Contrary to others we demonstrate that the fracture location alone is
      not sufficient to determine the stability of the distal radioulnar joint. 

PMID- 24573827
TI  - [Impact of soft tissue injury on results after osteosynthesis of intraarticular
      fractures of the base of the middle phalanx of the finger].
AB  - BACKGROUND: The aim of this study was to investigate retrospectively if soft
      tissue injuries have an impact on the functional results of surgically treated
      intra-articular fractures of the base of the middle phalanx. PATIENTS AND
      METHODS: From 1/2007 to 4/2010 we operated on 27 patients with intra-articular
      fractures of the base of the middle phalanx with pins, screws or external
      fixation analogous to Suzuki. 5 patients were excluded. 13 patients had no
      significant soft tissue injury (kWTV group), 9 patients had significant soft
      tissue damage including open fractures, skin lesions or/and severe soft tissue
      swelling (WTV group). Postoperative function and complications were analysed
      based on total active range of motion (TAM) and range of motion of the proximal
      interphalangeal joint (PIP-ROM) with regard to the Larsen score and clinical
      data. RESULTS: Fractures with soft tissue injuries had a significantly worse TAM
      outcome (p=0.04) than fractures without soft tissue injury (kWTV group: TAM 197.1
      degrees ; WTV group TAM 231.2 degrees ) even if the functional results regarding
      the Larsen classification were excellent or good in both groups (kWTV 100%, WTV
      88.9%). There were no significant differences regarding PIP-ROM of both groups.
      CONCLUSION: Soft tissue injuries have a negative impact on the functional results
      of surgical treated intra-articular fractures of the base of the middle phalanx.
      The influence on PIP-ROM might be less. Other factors might play a considerable
      role for PIP-ROM. With an adequate operative treatment most intra-articular
      middle phalanx fractures show good to excellent functional -results.

PMID- 24573828
TI  - Commentary on "Does ultrasonography contribute significantly to the diagnosis of
      carpal tunnel syndrome?" by A. Zyluk, I. Walaszek and z. Szlosser.
AB  - The diagnosis of carpal tunnel syndrome diagnosis can be made based on the
      history and clinical findings in most of the cases, but in doubtful cases,
      electrophysiological tests and ultrasound can provide additonal and useful
      information. 

PMID- 24573830
TI  - [Bipartite carpal scaphoid with osteonecrosis of the proximal pole - differential
      diagnosis of pseudarthrosis].
AB  - We report on the case of a young patient with bipartite carpal scaphoid with
      osteonecrosis of the proximal pole. The important differentiation of this entity
      to the pseudarthrosis of the scaphoid is discussed. 

PMID- 24573831
TI  - [DAHTH - quality in hand therapy].

PMID- 24573829
TI  - [Infection of the hand: evaluation of a two-stage therapy].
AB  - INTRODUCTION: Infections of the hand are common diseases in hand surgery
      departments. The correct diagnosis and subsequent treatment is difficult and is
      often underestimated. In literature different and often conflicting treatments
      are recommended. The present study retrospectively analysed our two-stage
      surgical treatment. PATIENTS AND METHODS: 60 patients (mean age: 51 years, 38
      male, 22 female) were studied retrospectively on the basis of the diagnosis hand
      infection (ICD L03.-). In all patients, a rapid and radical surgical debridement
      without wound closure was performed. An antibiotic therapy was initiated. We
      investigated how often wound closure during a second-look operation, following a
      period of open wound treatment with antiseptic dressing was successful possible.
      Furthermore, the patients were followed up in our outpatient clinic. RESULTS: A
      successful secondary wound closure was possible after on average 38.7 h and in
      92% of the patients. 8% of patients required further surgical treatment. These
      patients presented with either an existing disease or a delayed presentation with
      initial antibiotic treatment. Antibiotic therapy was performed on an average for
      8.7 days. Altogether for 85% of the 58 patients examined in our outpatient clinic
      the therapy could be terminated after 3 weeks with a full recovery of function of
      the injured hand and with full force measurements. The inability to work was on
      average 16 days. DISCUSSION: The two-stage surgical treatment, with radical
      debridement and open wound dressing in our collective is an adequate treatment
      for infections of the hand. It is a safe procedure, that allows for combination
      with an antibiotic therapy by which a rapid restoration of function of the
      injured hand is possible.

PMID- 24573832
TI  - [Commentary on the paper "Der "Wide Awake Approach" - Effizienz und
      Patientensicherheit bei der Karpaldachspaltung" by S. Low, D. Herold and C.
      Eingartner and on the Commentary by M. Dinkel about this Paper].

PMID- 24573834
TI  - Response to the letter to the editor of P. Mahapatra.

PMID- 24573833
TI  - "The wide-awake approach" - just one step to a streamlined carpal tunnel release
      service.

PMID- 24573835
TI  - A flexible and high-voltage internal tandem supercapacitor based on graphene
      based porous materials with ultrahigh energy density.
AB  - Pursuing higher working voltage and packaged energy density, an internal tandem
      supercapacitor has been successfully designed and fabricated based on graphene
      based porous carbon hybrid material. Compared with the packaged energy density of
      27.2 Wh kgcell (-1) and working voltage of 3.5 V using EMIMBF4 electrolyte for
      the conventional single-cell supercapacitor, the internal tandem device with the
      same material achieves a much higher working voltage of 7 V as well as a
      significantly improved energy density of 36.3 Wh kgcell (-1) (increased by 33%),
      which is also about 7 times of that of the state-of-art commercial
      supercapacitors. A flexible internal tandem device is also designed and
      fabricated and demonstrated similar excellent performance. 

PMID- 24573839
TI  - Co-culture with periodontal ligament stem cells enhances osteogenic gene
      expression in de-differentiated fat cells.
AB  - In recent decades, de-differentiated fat cells (DFAT cells) have emerged in
      regenerative medicine because of their trans-differentiation capability and the
      fact that their characteristics are similar to bone marrow mesenchymal stem
      cells. Even so, there is no evidence to support the osteogenic induction using
      DFAT cells in periodontal regeneration and also the co-culture system.
      Consequently, this study sought to evaluate the DFAT cells co-culture with
      periodontal ligament stem cells (PDLSCs) in vitro in terms of gene expression by
      comparing runt-related transcription factor 2 (RUNX2) and Peroxisome proliferator
      activated receptor gamma 2 (PPARgamma2) genes. We isolated DFAT cells from mature
      adipocytes and compared proliferation with PDLSCs. After co-culture with PDLSCs,
      we analyzed transcriptional activity implying by DNA methylation in all
      adipogenic gene promoters using combined bisulfite restriction analysis. We
      compared gene expression in RUNX2 gene with the PPARgamma2 gene using
      quantitative RT-PCR. After being sub-cultured, DFAT cells demonstrated morphology
      similar to fibroblast-like cells. At the same time, PDLSCs established all stem
      cell characteristics. Interestingly, the co-culture system attenuated
      proliferation while enhancing osteogenic gene expression in RUNX2 gene. Using the
      co-culture system, DFAT cells could trans-differentiate into osteogenic lineage
      enhancing, but conversely, their adipogenic characteristic diminished. Therefore,
      DFAT cells and the co-culture system might be a novel cell-based therapy for
      promoting osteogenic differentiation in periodontal regeneration. 

PMID- 24573840
TI  - Shark fin, a symbol of wealth and good fortune may pose health risks: the case of
      mercury.
AB  - There is a lack of information concerning human health risks due to exposure to
      mercury contained in shark fins, through dietary intake. Health risk assessment
      of shark fins, collected from 5 cities in China: Hong Kong (HK), Beijing,
      Shanghai (SH), Haikou (HN) and Wenzhou (WZ), was conducted, based on total
      mercury and methylmercury, and analyzed by a cold vapor atomic fluorescence
      spectrometry equipped with high-performance liquid chromatography, respectively.
      The results showed that 16.8 % samples from HK, 8.3 % from SH, 33.3 % from HN,
      and 16.8 % from WZ were regarded as unsafe for human consumption. Extremely high
      consumption rates of shark fins for an adult and a child (0.150 and 0.0807
      kg/day, respectively), at 95th centile, samples from WZ demonstrated high non
      cancer risks (adverse health effects) (Hazard Quotient = 16.0) on adults (aged 25
      65), and samples from SH, HN and WZ also showed high non-cancer risks (Hazard
      Quotient = 12.9, 21.0, and 34.4, respectively) on children (aged 1-7).
      Consumption of shark fins may be detrimental to human health. 

PMID- 24573841
TI  - Integrating scientific guidance into marine spatial planning.
AB  - Marine spatial planning (MSP), whereby areas of the ocean are zoned for different
      uses, has great potential to reduce or eliminate conflicts between competing
      management goals, but only if strategically applied. The recent literature
      overwhelmingly agrees that including stakeholders in these planning processes is
      critical to success; but, given the countless alternative ways even simple
      spatial regulations can be configured, how likely is it that a stakeholder-driven
      process will generate plans that deliver on the promise of MSP? Here, we use a
      spatially explicit, dynamic bioeconomic model to show that stakeholder-generated
      plans are doomed to fail in the absence of strong scientific guidance. While
      strategically placed spatial regulations can improve outcomes remarkably, the
      vast majority of possible plans fail to achieve this potential. Surprisingly,
      existing scientific rules of thumb do little to improve outcomes. Here, we
      develop an alternative approach in which models are used to identify efficient
      plans, which are then modified by stakeholders. Even if stakeholders alter these
      initial proposals considerably, results hugely outperform plans guided by
      scientific rules of thumb. Our results underscore the importance of spatially
      explicit dynamic models for the management of marine resources and illustrate how
      such models can be harmoniously integrated into a stakeholder-driven MSP process.

PMID- 24573842
TI  - Phenotypic and genomic plasticity of alternative male reproductive tactics in
      sailfin mollies.
AB  - A major goal of modern evolutionary biology is to understand the causes and
      consequences of phenotypic plasticity, the ability of a single genotype to
      produce multiple phenotypes in response to variable environments. While
      ecological and quantitative genetic studies have evaluated models of the
      evolution of adaptive plasticity, some long-standing questions about plasticity
      require more mechanistic approaches. Here, we address two of those questions:
      does plasticity facilitate adaptive evolution? And do physiological costs place
      limits on plasticity? We examine these questions by comparing genetically and
      plastically regulated behavioural variation in sailfin mollies (Poecilia
      latipinna), which exhibit striking variation in plasticity for male mating
      behaviour. In this species, some genotypes respond plastically to a change in the
      social environment by switching between primarily courting and primarily sneaking
      behaviour. In contrast, other genotypes have fixed mating strategies (either
      courting or sneaking) and do not display plasticity. We found that genetic and
      plastic variation in behaviour were accompanied by partially, but not completely
      overlapping changes in brain gene expression, in partial support of models that
      predict that plasticity can facilitate adaptive evolution. We also found that
      behavioural plasticity was accompanied by broader and more robust changes in
      brain gene expression, suggesting a substantial physiological cost to plasticity.
      We also observed that sneaking behaviour, but not courting, was associated with
      upregulation of genes involved in learning and memory, suggesting that sneaking
      is more cognitively demanding than courtship. 

PMID- 24573843
TI  - Efficiency of partner choice and sanctions in Lotus is not altered by nitrogen
      fertilization.
AB  - Eukaryotic hosts must exhibit control mechanisms to select against ineffective
      bacterial symbionts. Hosts can minimize infection by less-effective symbionts
      (partner choice) and can divest of uncooperative bacteria after infection
      (sanctions). Yet, such host-control traits are predicted to be context dependent,
      especially if they are costly for hosts to express or maintain. Legumes form
      symbiosis with rhizobia that vary in symbiotic effectiveness (nitrogen fixation)
      and can enforce partner choice as well as sanctions. In nature, legumes acquire
      fixed nitrogen from both rhizobia and soils, and nitrogen deposition is rapidly
      enriching soils globally. If soil nitrogen is abundant, we predict host control
      to be downregulated, potentially allowing invasion of ineffective symbionts. We
      experimentally manipulated soil nitrogen to examine context dependence in host
      control. We co-inoculated Lotus strigosus from nitrogen depauperate soils with
      pairs of Bradyrhizobium strains that vary in symbiotic effectiveness and
      fertilized plants with either zero nitrogen or growth maximizing nitrogen. We
      found efficient partner choice and sanctions regardless of nitrogen
      fertilization, symbiotic partner combination or growth season. Strikingly, host
      control was efficient even when L. strigosus gained no significant benefit from
      rhizobial infection, suggesting that these traits are resilient to short-term
      changes in extrinsic nitrogen, whether natural or anthropogenic. 

PMID- 24573844
TI  - Feeding biomechanics in Acanthostega and across the fish-tetrapod transition.
AB  - Acanthostega is one of the earliest and most primitive limbed vertebrates. Its
      numerous fish-like features indicate a primarily aquatic lifestyle, yet cranial
      suture morphology suggests that its skull is more similar to those of terrestrial
      taxa. Here, we apply geometric morphometrics and two-dimensional finite-element
      analysis to the lower jaws of Acanthostega and 22 other tetrapodomorph taxa in
      order to quantify morphological and functional changes across the fish-tetrapod
      transition. The jaw of Acanthostega is similar to that of certain tetrapodomorph
      fish and transitional Devonian taxa both morphologically (as indicated by its
      proximity to those taxa in morphospace) and functionally (as indicated by the
      distribution of stress values and relative magnitude of bite force). Our results
      suggest a slow tempo of morphological and biomechanical changes in the transition
      from Devonian tetrapod jaws to aquatic/semi-aquatic Carboniferous tetrapod jaws.
      We conclude that Acanthostega retained a primitively aquatic lifestyle and did
      not possess cranial adaptations for terrestrial feeding. 

PMID- 24573845
TI  - Endocranial morphology of Palaeocene Plesiadapis tricuspidens and evolution of
      the early primate brain.
AB  - Expansion of the brain is a key feature of primate evolution. The fossil record,
      although incomplete, allows a partial reconstruction of changes in primate brain
      size and morphology through time. Palaeogene plesiadapoids, closest relatives of
      Euprimates (or crown-group primates), are crucial for understanding early
      evolution of the primate brain. However, brain morphology of this group remains
      poorly documented, and major questions remain regarding the initial phase of
      euprimate brain evolution. Micro-CT investigation of the endocranial morphology
      of Plesiadapis tricuspidens from the Late Palaeocene of Europe--the most complete
      plesiadapoid cranium known--shows that plesiadapoids retained a very small and
      simple brain. Plesiadapis has midbrain exposure, and minimal encephalization and
      neocorticalization, making it comparable with that of stem rodents and
      lagomorphs. However, Plesiadapis shares a domed neocortex and downwardly shifted
      olfactory-bulb axis with Euprimates. If accepted phylogenetic relationships are
      correct, then this implies that the euprimate brain underwent drastic
      reorganization during the Palaeocene, and some changes in brain structure
      preceded brain size increase and neocortex expansion during evolution of the
      primate brain.

PMID- 24573846
TI  - The making of a pest: the evolution of a fruit-penetrating ovipositor in
      Drosophila suzukii and related species.
AB  - Evolutionary innovation can allow a species access to a new ecological niche,
      potentially reducing competition with closely related species. While the vast
      majority of Drosophila flies feed on rotting fruit and other decaying matter, and
      are harmless to human activity, Drosophila suzukii, which has a morphologically
      modified ovipositor, is capable of colonizing live fruit that is still in the
      process of ripening, causing massive agricultural damage. Here, we conducted the
      first comparative analysis of this species and its close relatives, analysing
      both ovipositor structure and fruit susceptibility. We found that the ovipositor
      of the species most closely related to D. suzukii, Drosophila subpulchrella, has
      a similar number of enlarged, evolutionarily derived bristles, but a notably
      different overall shape. Like D. suzukii, D. subpulchrella flies are capable of
      puncturing the skin of raspberries and cherries, but we found no evidence that
      they could penetrate the thicker skin of two varieties of grapes. More distantly
      related species, one of which has previously been mistaken for D. suzukii, have
      blunt ovipositors with small bristles. While they did not penetrate fruit skin in
      any of the assays, they readily colonized fruit interiors where the skin was
      broken. Our results suggest that considering evolutionary context may be
      beneficial to the management of invasive species. 

PMID- 24573847
TI  - Distinctive convergence in Australian floral colours seen through the eyes of
      Australian birds.
AB  - We used a colour-space model of avian vision to assess whether a distinctive bird
      pollination syndrome exists for floral colour among Australian angiosperms. We
      also used a novel phylogenetically based method to assess whether such a syndrome
      represents a significant degree of convergent evolution. About half of the 80
      species in our sample that attract nectarivorous birds had floral colours in a
      small, isolated region of colour space characterized by an emphasis on long
      wavelength reflection. The distinctiveness of this 'red arm' region was much
      greater when colours were modelled for violet-sensitive (VS) avian vision than
      for the ultraviolet-sensitive visual system. Honeyeaters (Meliphagidae) are the
      dominant avian nectarivores in Australia and have VS vision. Ancestral state
      reconstructions suggest that 31 lineages evolved into the red arm region, whereas
      simulations indicate that an average of five or six lineages and a maximum of 22
      are likely to have entered in the absence of selection. Thus, significant
      evolutionary convergence on a distinctive floral colour syndrome for bird
      pollination has occurred in Australia, although only a subset of bird-pollinated
      taxa belongs to this syndrome. The visual system of honeyeaters has been the
      apparent driver of this convergence. 

PMID- 24573848
TI  - Male cognitive performance declines in the absence of sexual selection.
AB  - Sexual selection is responsible for the evolution of male ornaments and
      armaments, but its role in the evolution of cognition--the ability to process,
      retain and use information--is largely unexplored. Because successful courtship
      is likely to involve processing information in complex, competitive sexual
      environments, we hypothesized that sexual selection contributes to the evolution
      and maintenance of cognitive abilities in males. To test this, we removed mate
      choice and mate competition from experimental populations of Drosophila
      melanogaster by enforcing monogamy for over 100 generations. Males evolved under
      monogamy became less proficient than polygamous control males at relatively
      complex cognitive tasks. When faced with one receptive and several unreceptive
      females, polygamous males quickly focused on receptive females, whereas
      monogamous males continued to direct substantial courtship effort towards
      unreceptive females. As a result, monogamous males were less successful in this
      complex setting, despite being as quick to mate as their polygamous counterparts
      with only one receptive female. This diminished ability to use past information
      was not limited to the courtship context: monogamous males (but not females) also
      showed reduced aversive olfactory learning ability. Our results provide direct
      experimental evidence that the intensity of sexual selection is an important
      factor in the evolution of male cognitive ability.

PMID- 24573850
TI  - Life-history specialization was not an evolutionary dead-end in Pyrenean cave
      beetles.
AB  - Research on subterranean organisms has focused on the colonization process and
      some of the associated phenotypic changes, but little is known on the long-term
      evolutionary dynamics of subterranean lineages and the origin of some highly
      specialized complex characters. One of the most extreme modifications is the
      reduction of the number of larval instars in some Leptodirini beetles from the
      ancestral 3 to 2 and ultimately a single instar. This reduction is usually
      assumed to have occurred independently multiple times within the same lineage and
      geographical area, but its evolution has never been studied in a phylogenetic
      framework. Using a comprehensive molecular phylogeny, we found a low number of
      independent origins of the reduction in the number of instars, with a single
      transition, dated to the Oligocene-Miocene, from 3 to 2 and then 1 instar in the
      Pyrenees, the best-studied area. In the Pyrenees, the 1-instar lineage had a
      diversification rate (0.22 diversification events per lineage per million years)
      significantly higher than that of 3- or 2-instar lineages (0.10), and similar to
      that seen in other Coleopteran radiations. Far from being evolutionary dead-ends,
      ancient lineages fully adapted to subterranean life seem able to persist and
      diversify over long evolutionary periods. 

PMID- 24573851
TI  - Positional specification in the segmental growth pattern of an early arthropod.
AB  - In many arthropods, there is a change in relative segment size during post
      embryonic development, but how segment differential growth is produced is little
      known. A new dataset of the highest quality specimens of the 429 Myr old
      trilobite Aulacopleura koninckii provides an unparalleled opportunity to
      investigate segment growth dynamics and its control in an early arthropod.
      Morphometric analysis across nine post-embryonic stages revealed a growth
      gradient in the trunk of A. koninckii. We contrastively tested different growth
      models referable to two distinct hypotheses of growth control for the developing
      trunk: (i) a segment-specific control, with individual segments having
      differential autonomous growth progression, and (ii) a regional control, with
      segment growth depending on their relative position along the main axis. We show
      that the trunk growth pattern of A. koninckii was consistent with a regional
      growth control producing a continuous growth gradient that was stable across all
      developmental stages investigated. The specific posterior-to-anterior decaying
      shape of the growth gradient suggests it deriving from the linear transduction of
      a graded signal, similar to those commonly provided by morphogens. A growth
      control depending on a form of positional specification, possibly realized
      through the linear interpretation of a graded signal, may represent the primitive
      condition for arthropod differential growth along the main body axis, from which
      the diverse and generally more complex forms of growth control in subsequent
      arthropods have evolved. 

PMID- 24573849
TI  - Was skin cancer a selective force for black pigmentation in early hominin
      evolution?
AB  - Melanin provides a crucial filter for solar UV radiation and its genetically
      determined variation influences both skin pigmentation and risk of cancer.
      Genetic evidence suggests that the acquisition of a highly stable melanocortin 1
      receptor allele promoting black pigmentation arose around the time of savannah
      colonization by hominins at some 1-2 Ma. The adaptive significance of dark skin
      is generally believed to be protection from UV damage but the pathologies that
      might have had a deleterious impact on survival and/or reproductive fitness,
      though much debated, are uncertain. Here, I suggest that data on age-associated
      cancer incidence and lethality in albinos living at low latitudes in both Africa
      and Central America support the contention that skin cancer could have provided a
      potent selective force for the emergence of black skin in early hominins. 

PMID- 24573852
TI  - Fifty million years of herbivory on coral reefs: fossils, fish and functional
      innovations.
AB  - The evolution of ecological processes on coral reefs was examined based on Eocene
      fossil fishes from Monte Bolca, Italy and extant species from the Great Barrier
      Reef, Australia. Using ecologically relevant morphological metrics, we
      investigated the evolution of herbivory in surgeonfishes (Acanthuridae) and
      rabbitfishes (Siganidae). Eocene and Recent surgeonfishes showed remarkable
      similarities, with grazers, browsers and even specialized, long-snouted forms
      having Eocene analogues. These long-snouted Eocene species were probably pair
      forming, crevice-feeding forms like their Recent counterparts. Although Eocene
      surgeonfishes likely played a critical role as herbivores during the origins of
      modern coral reefs, they lacked the novel morphologies seen in modern Acanthurus
      and Siganus (including eyes positioned high above their low-set mouths). Today,
      these forms dominate coral reefs in both abundance and species richness and are
      associated with feeding on shallow, exposed algal turfs. The radiation of these
      new forms, and their expansion into new habitats in the Oligocene-Miocene,
      reflects the second phase in the development of fish herbivory on coral reefs
      that is closely associated with the exploitation of highly productive short algal
      turfs. 

PMID- 24573853
TI  - Action anticipation in human infants reveals assumptions about anteroposterior
      body-structure and action.
AB  - Animal actions are almost universally constrained by the bilateral body-plan. For
      example, the direction of travel tends to be constrained by the orientation of
      the animal's anteroposterior axis. Hence, an animal's behaviour can reliably
      guide the identification of its front and back, and its orientation can reliably
      guide action prediction. We examine the hypothesis that the evolutionarily
      ancient relation between anteroposterior body-structure and behaviour guides our
      cognitive processing of agents and their actions. In a series of studies, we
      demonstrate that, after limited exposure, human infants as young as six months of
      age spontaneously encode a novel agent as having a certain axial direction with
      respect to its actions and rely on it when anticipating the agent's further
      behaviour. We found that such encoding is restricted to objects exhibiting cues
      of agency and does not depend on generalization from features of familiar
      animals. Our research offers a new tool for investigating the perception of
      animate agency and supports the proposal that the underlying cognitive mechanisms
      have been shaped by basic biological adaptations in humans. 

PMID- 24573855
TI  - Repeated mass strandings of Miocene marine mammals from Atacama Region of Chile
      point to sudden death at sea.
AB  - Marine mammal mass strandings have occurred for millions of years, but their
      origins defy singular explanations. Beyond human causes, mass strandings have
      been attributed to herding behaviour, large-scale oceanographic fronts and
      harmful algal blooms (HABs). Because algal toxins cause organ failure in marine
      mammals, HABs are the most common mass stranding agent with broad geographical
      and widespread taxonomic impact. Toxin-mediated mortalities in marine food webs
      have the potential to occur over geological timescales, but direct evidence for
      their antiquity has been lacking. Here, we describe an unusually dense
      accumulation of fossil marine vertebrates from Cerro Ballena, a Late Miocene
      locality in Atacama Region of Chile, preserving over 40 skeletons of rorqual
      whales, sperm whales, seals, aquatic sloths, walrus-whales and predatory bony
      fish. Marine mammal skeletons are distributed in four discrete horizons at the
      site, representing a recurring accumulation mechanism. Taphonomic analysis points
      to strong spatial focusing with a rapid death mechanism at sea, before being
      buried on a barrier-protected supratidal flat. In modern settings, HABs are the
      only known natural cause for such repeated, multispecies accumulations. This
      proposed agent suggests that upwelling zones elsewhere in the world should
      preserve fossil marine vertebrate accumulations in similar modes and densities. 

PMID- 24573854
TI  - Genotyping of ancient Mycobacterium tuberculosis strains reveals historic genetic
      diversity.
AB  - The evolutionary history of the Mycobacterium tuberculosis complex (MTBC) has
      previously been studied by analysis of sequence diversity in extant strains, but
      not addressed by direct examination of strain genotypes in archaeological
      remains. Here, we use ancient DNA sequencing to type 11 single nucleotide
      polymorphisms and two large sequence polymorphisms in the MTBC strains present in
      10 archaeological samples from skeletons from Britain and Europe dating to the
      second-nineteenth centuries AD. The results enable us to assign the strains to
      groupings and lineages recognized in the extant MTBC. We show that at least
      during the eighteenth-nineteenth centuries AD, strains of M. tuberculosis
      belonging to different genetic groups were present in Britain at the same time,
      possibly even at a single location, and we present evidence for a mixed infection
      in at least one individual. Our study shows that ancient DNA typing applied to
      multiple samples can provide sufficiently detailed information to contribute to
      both archaeological and evolutionary knowledge of the history of tuberculosis. 

PMID- 24573856
TI  - Social complementation and growth advantages promote socially defective bacterial
      isolates.
AB  - Social interactions among diverse individuals that encounter one another in
      nature have often been studied among animals but rarely among microbes. For
      example, the evolutionary forces that determine natural frequencies of bacteria
      that express cooperative behaviours at low levels remain poorly understood.
      Natural isolates of the soil bacterium Myxococcus xanthus sampled from the same
      fruiting body often vary in social phenotypes, such as group swarming and
      multicellular development. Here, we tested whether genotypes highly proficient at
      swarming or development might promote the persistence of less socially proficient
      genotypes from the same fruiting body. Fast-swarming strains complemented slower
      isolates, allowing the latter to keep pace with faster strains in mixed groups.
      During development, one low-sporulating strain was antagonized by high
      sporulators, whereas others with severe developmental defects had those defects
      partially complemented by high-sporulating strains. Despite declining in
      frequency overall during competition experiments spanning multiple cycles of
      development, developmentally defective strains exhibited advantages during the
      growth phases of competitions. These results suggest that microbes with low
      sociality phenotypes often benefit from interacting with more socially proficient
      strains. Such complementation may combine with advantages at other traits to
      increase equilibrium frequencies of low-sociality genotypes in natural
      populations. 

PMID- 24573859
TI  - Current progress on internal medicine in China-2006 part I.
AB  - The growing interest has been placed in the current state of China's internal
      medicine from all over the world. Many data of internal medicine in China were
      collected by searching through some of the most prominent medical magazines
      published in China in 2006. Because there are many researches on the field of
      internal medicine, just some representative reports focusing on this topic were
      selected in this paper. In part I of this study, a summary of the advances made
      in cardiology, respiration diseases, and gastroenterology was presented. 

PMID- 24573858
TI  - The total burden of rare, non-synonymous exome genetic variants is not associated
      with childhood or late-life cognitive ability.
AB  - Human cognitive ability shows consistent, positive associations with fitness
      components across the life-course. Underlying genetic variation should therefore
      be depleted by selection, which is not observed. Genetic variation in general
      cognitive ability (intelligence) could be maintained by a mutation-selection
      balance, with rare variants contributing to its genetic architecture. This study
      examines the association between the total number of rare stop-gain/loss, splice
      and missense exonic variants and cognitive ability in childhood and old age in
      the same individuals. Exome array data were obtained in the Lothian Birth Cohorts
      of 1921 and 1936 (combined N = 1596). General cognitive ability was assessed at
      age 11 years and in late life (79 and 70 years, respectively) and was modelled
      against the total number of stop-gain/loss, splice, and missense exonic variants,
      with minor allele frequency less than or equal to 0.01, using linear regression
      adjusted for age and sex. In both cohorts and in both the childhood and late-life
      models, there were no significant associations between rare variant burden in the
      exome and cognitive ability that survived correction for multiple testing.
      Contrary to our a priori hypothesis, we observed no evidence for an association
      between the total number of rare exonic variants and either childhood cognitive
      ability or late-life cognitive ability. 

PMID- 24573860
TI  - Involvement of p38 mitogen-activated protein kinase in the regulation of platelet
      derived growth factor -induced cell migration.
AB  - The aim of this study was to investigate the role of p38 mitogen-activated
      protein kinase (MAPK) in cell migration induced by platelet-derived growth factor
      (PDGF). Western blot was performed to detect the phosphorylation of p38 in NIH3T3
      cells treated with PDGF. A Transwell cell migration system was used to determine
      the effects of PDGF treatment on the migration of NIH3T3 cells and the influence
      of p38 deficiency on this process in a p38 gene knockout (p38(-/-)) mouse
      embryonic fibroblast cell line. On the stimulation of PDGF, the migration of
      NIH3T3 cells was significantly increased (P < 0.001) compared to the control and
      p38 MAP kinase was simultaneously phosphorylated. Furthermore, the PDGF-induced
      cell migration was significantly blocked in p38 gene knockout (p38(-/-)) mouse
      embryonic fibroblasts (MEFs) (P < 0.001) as compared with the wild type cells
      (p38(+/+)). p38 MAPK plays an important role in the regulation of cell migration
      induced by PDGF. 

PMID- 24573857
TI  - Long-term variation in influenza A virus prevalence and subtype diversity in
      migratory mallards in northern Europe.
AB  - Data on long-term circulation of pathogens in wildlife populations are seldom
      collected, and hence understanding of spatial-temporal variation in prevalence
      and genotypes is limited. Here, we analysed a long-term surveillance series on
      influenza A virus (IAV) in mallards collected at an important migratory stopover
      site from 2002 to 2010, and characterized seasonal dynamics in virus prevalence
      and subtype diversity. Prevalence dynamics were influenced by year, but retained
      a common pattern for all years whereby prevalence was low in spring and summer,
      but increased in early autumn with a first peak in August, and a second more
      pronounced peak during October-November. A total of 74 haemagglutinin
      (HA)/neuraminidase (NA) combinations were isolated, including all NA and most HA
      (H1-H12) subtypes. The most common subtype combinations were H4N6, H1N1, H2N3,
      H5N2, H6N2 and H11N9, and showed a clear linkage between specific HA and NA
      subtypes. Furthermore, there was a temporal structuring of subtypes within
      seasons based on HA phylogenetic relatedness. Dissimilar HA subtypes tended to
      have different temporal occurrence within seasons, where the subtypes that
      dominated in early autumn were rare in late autumn, and vice versa. This suggests
      that build-up of herd immunity affected IAV dynamics in this system. 

PMID- 24573861
TI  - Construction of Hsp90beta gene specific silencing plasmid and its transfection
      efficiency.
AB  - The purpose of this work was to construct the plasmid that could direct the
      synthesis of siRNA-like transcripts and thus mediate strong and specific
      repression of human heat shock protein 90beta (Hsp90beta) gene expression and to
      compare the transfection efficiency of the plasmids in varying conditions of
      transfection. Three 64 nt oligos corresponding to different regions of the target
      gene were chemically synthesized and annealed and were then ligated with pSUPER
      EGFP1 plasmid and double-digested with HindIII and BglII. Recombinant plasmids
      were transformed into Escherichia coli, DH5a, and the colonies were picked and
      grown in the Amp-agarose. The presence of positive clones was checked by the
      means of endodigestion and sequencing. Three cell strains, HepG2, Human umbilicus
      vein endothelium cells (HUVEC) and HeK293, were cultured. Then the plasmids were
      transfected into the cells at different ratios of plasmid to Lipofectamine. The
      transfection efficiency was measured by detection of enhanced green fluorescence
      protein (EGFP). The presence of positive recombinant clones were verified by
      double-digestion and sequencing. The bases inserted into the plasmids were
      correct and the positive colonies were named pSuper-Hsp90beta1, pSuper-Hsp90beta2
      and pSuper-Hsp90beta3. After optimizing the ratio of plasmid to Lipofectamine, we
      achieved high transfection efficiency in HeK293 cells. Transfection efficiency
      was still low in the HepG2 cells. In conclusion, the si-RNA-synthesizing plasmids
      targeting Hsp90beta were constructed and transfected into cells with different
      transfection efficiency. 

PMID- 24573862
TI  - Observations on pathological and histochemical changes in piglet livers infected
      with Taenia saginata asiatica.
AB  - To study the pathological and histochemical characteristics of lesions in piglet
      livers infected with Taenia saginata asiatica (T. saginata asiatica) throughout
      the different stages, piglets were fed with eggs of T. saginata asiatica and
      raised in isolation in an animal center to establish the T. saginata asiatica
      infection model with normal piglets as control. The pathological changes in the
      piglet livers were observed after the infection using liver sections stained with
      hematoxylin and eosin. Histochemical methods were used to check the changes in
      lipid, glycogen and protein content in the liver. The data collected by image
      analysis were analyzed statistically with Statistical Package for the Social
      Science. The results show that T. saginata asiatica-exposed piglets were indeed
      infected. Inflammatory reactions began on the fourth day and progressed rapidly.
      Kupffer cell hyperplasia, hepatic hydropic degeneration and ballooning
      degeneration were found in the 10th-20th days after infection. Hepatic central
      veins and hepatic sinusoids were dilated and congested. Spotty necrosis occurred
      in some local liver tissues. In the 40th-60th days, granulomatous reactions and
      mild hepatocirrhosis were the main lesions. In the 70th-80th days,
      hepatocirrhosis and bile duct proliferation were observed in the liver. In the
      different stages, lipid drops were increased while glycogen and protein levels
      were decreased to some degree. There was a significant difference in metabolism
      between the infected group and the control group (P < 0.01). It is concluded that
      pigs are the favorable intermediate host of T. saginata asiatica and its
      infection can result in serious pathological and histochemical lesions in host
      organs. 

PMID- 24573864
TI  - Influence and related mechanism of Retn gene expression on glucose uptake in 3T3
      L1 cells.
AB  - The aim of this article was to investigate the influence and the related
      mechanism of the Retn gene on glucose uptake and insulin resistance in 3T3-L1
      cells. Radioimmuno-assay was used to determine glucose uptake in 3T3-L1 cells
      with different Retn gene expression levels, whether cells were stimulated by
      insulin or not. RT-PCR and real-time RT-PCR analysis were used to determine the
      mRNA levels of several glucose transport proteins in 3T3-L1 cells with different
      Retn gene expression levels, including insulin receptor substrate-1(IRS-1),
      phosphatidylinositol 3-kinase (PI-3K), AKT-2, glucose transporter-4 (GLUT-4), p38
      mitogen-activated protein kinase (p38MAPK) and glycogen synthase kinase-3beta
      (GSK-3beta). The glucose uptake decreased with the increase in Retn gene
      expression in 3T3-L1 cells, which was independent of whether the cells were
      stimulated by insulin or not. The mRNA expression of two signal proteins PI-3K
      and AKT-2 decreased and the other two signal proteins, GSK-3beta and p38MAPK,
      increased with Retn overexpression in 3T3-L1 cells. Resistin could induce insulin
      resistance in adipocytes, which might be related to the changes of some proteins
      in PI-3K and Ras pathways. 

PMID- 24573863
TI  - Immunohistochemical characterization of hepatic stem cell-related cells in
      developing human liver.
AB  - Little is known about the expression characteristics of the various kinds of
      possible markers in hepatic stem cells (HSCs) and other HSC-related cells in
      human fetal liver in various developmental stages. It is significant to
      investigate the immunohistochemical expression for better understanding of the
      origin, differentiation and migration of HSCs in the developing human liver. H-E
      staining and immunohistochemical methods were used to observe the expression of
      hepatic/cholangiocellular differentiation markers (AFP, GST-pi, CK7, CK19) and
      hematopoietic stem cell markers(CD34 and c-kit) in several kinds of HSC-related
      cells in thirty cases of fetal liver samples (4-35 weeks after pregnancy). AFP
      expression appears in fetal hepatocytes at four weeks' gestation. It peaks at 16
      24 weeks' gestation and decreases gradually afterwards. Finally, weak signals
      were only found in some ductal plate cells and a few limiting plate cells. GST-pi
      was detected in hepatic cord cells from the sixth week and in the ductal plate
      cells from the eighth week. Twenty-six weeks later, only some ductal plate cells
      and a few limiting plate cells show positive signals. CK19 expression peaks
      during the 6th-11th weeks in hepatic cord cells and decreases gradually
      afterwards, except for the ductal plates. CK7 expression was limited in the
      ductal plate cells and bile ducts cells from the 14th week. CD34 and c-kit were
      detected at the eighth week in some ductal plate cells and a few mononuclear
      cells in the hepatic cords/mesenchymal tissue of portal areas. After 21 weeks,
      CD34 and c-kit were found only in ductal plate cells and a few mononuclear cells
      in the hepatic mesenchymal tissue of portal areas. Fetal hepatocytes at 4-16
      weeks' gestation are mainly constituted by HSCs characterized with bi-potential
      differentiation capacity. At 16 weeks' gestation, most hepatic cord cells begin
      to differentiate into hepatocytes and abundant HSCs remain in ductal plate (the
      origin site of Hering canals). It is also indicated that the hematopoietic stem
      cells may give rise to some HSCs in embryonic liver. These indirectly support the
      hypothesis about the location and origin of HSCs in "liver valley hypothesis"
      reported previously. 

PMID- 24573865
TI  - Evaluation of the relative risk of stroke in patients with hypertension using
      cerebrovascular hemodynamic accumulative score.
AB  - The relative risk (RR) of stroke in patients with hypertension was evaluated by
      using synthetic index of cerebrovascular hemodynamics. A total of 7,371 patients
      with hypertension with ages >=40 years were selected from a population-based
      cohort study of the risk factors for stroke. The data on the baseline
      investigation of risk factors, the determination of cerebrovascular hemodynamic
      parameters (CVHP), and stroke follow-up were analyzed. The RR of stroke in
      patients with hypertension was evaluated by CVHP scores. Univariate analysis
      indicated that hypertension, complicated by other risk factors, had significant
      statistical association with the onset of stroke. RRs for stroke when
      hypertension complicated with decrease of hemodynamic scores, heart disease,
      cigarette smoking and alcohol consumption were 4.93 (95%CI, 3.26-7.45), 1.90
      (95%CI, 1.36-2.66), 1.99 (95%CI, 1.42-2.79) and 1.73 (95%CI, 1.19-2.53)
      respectively. In multivariate analysis, hemodynamic score, age, sex, cigarette
      smoking, family history of stroke and systolic blood pressure were selected by
      the Cox regression for inclusion in the final analysis. Among them, the RR of
      hemodynamic score was highest. The analysis of dose-response relationships
      indicated that when the hemodynamic scores in patients with hypertension were
      lower than 75 points, the RR of stroke at 75, 60, 45, 30 and 15 points were 2.85,
      4.43, 4.54, 5.40 and 9.88, respectively. The risk of stroke in patients with
      hypertension is closely associated with hemodynamic impairment and the
      hemodynamic score may be used for quantitative evaluation of relative risks of
      stroke. 

PMID- 24573866
TI  - Partial portacaval shunt with H-grafts to treat portal hypertension.
AB  - Partial portosystemic shunts have been popularized because of a reported low rate
      of mortality and morbidity (especially encephalopathy, liver failure and
      occlusion). The results of partial portacaval shunts [small-diameter expanded
      polytetrafluoroethylene (ePTFE) H-graft portacaval shunt] were retrospectively
      reviewed to evaluate the clinical efficacy in the treatment of portal
      hypertension. Forty-three patients with portal hypertension were treated by small
      diameter H-graft of ePTFE portacaval shunt from May 1995 to April 2006. Thirty
      three had externally ringed grafts and ten had non-ringed ones. Ten had grafts of
      10 mm in diameter and 33 had grafts of 8 mm. The left gastric artery and coronary
      vein were ligated in all the cases. Six had pericardial devascularization and
      splenectomy was performed in 42. An average decrease of free portal pressure
      (FPP) from (33.24 +/- 4.78) cmH2O before shunting and (13.65 +/- 5.65) cmH2O
      after shunting was observed. The portal blood flow was reduced by one-third of
      that before shunt. Thirty-eight patients survived and no upper gastro-intestinal
      rebleeding occurred in the follow-up period (50.5 months in average). Two were
      out of contact. Color Doppler ultrasonography and/or portography revealed the
      shunts were patent in 38 cases and were occluded in three cases (3/41, 7.3%).
      Encephalopathy developed in five cases (5/41, 12.2%). Partial (small-diameter
      ePTFE H-graft) portacaval shunting can reduce the portal pressure effectively.
      Majority of the hepatic flow from the portal vein can be maintained adequately.
      The shunts with reinforced grafts can keep a higher rate of patency. The
      morbidity of encephalopathy was lower than those with total shunt. The partial
      portacaval shunt is effective in preventing recurrent variceal bleeding. 

PMID- 24573867
TI  - Emergency adult living donor right lobe liver transplantation for fulminant
      hepatic failure.
AB  - Fulminant hepatitis is fatal in most cases and timely liver transplantation is
      the only effective treatment. This study evaluates the survival outcomes of
      patients who underwent living-donor liver transplantation (LDLT) using right lobe
      liver grafts for fulminant liver failure due to hepatitis B infection. Nine cases
      of adult right lobe LDLT were performed in our department from September 2002 to
      August 2005 and the clinical and following-up data were reviewed. According to
      the pre-transplant Child-Pugh-Turcotte classification, the nine patients were
      classified as grade C. The model for end-stage liver disease (MELD) score of
      these patients ranged from 16 to 42. The principal complications before
      transplantation included abnormal renal function, hepatic coma of different
      degrees and alimentary tract hemorrhage. The main complications after
      transplantation included pulmonary infection in two cases, acute renal failure in
      three cases and transplantation-related encephalopathy in one case. No primary
      failure of vascular or biliary complications occurred. The one-year survival rate
      was 55.6%. There were no serious complications or deaths in donors. In general,
      it is extremely difficult to treat fulminant hepatitis by conservative regimen,
      particularly, in cases with rapid progression. Emergency adult living-donor liver
      transplantation is an effective treatment for fulminant hepatitis patients and is
      relatively safe for donors. 

PMID- 24573868
TI  - Effects of parenteral nutrition with and without GH on the GH/IGF-1 axis after
      hepatectomy in hepatocellular carcinoma with liver cirrhosis.
AB  - Postoperative hepatic insulin-like growth factor-1 (IGF-1) production may be
      severely disturbed in patients with liver cirrhosis. Complex alterations in the
      GH/IGF-1 axis are thought to play an important role in the protein catabolism
      that complicates major surgical procedures. The aim of this study was to explore
      the effects of parenteral nutrition (PN) with and without growth hormone (GH) on
      the GH/IGF-1 axis after hepatectomy for hepatocellular carcinoma (HCC) with
      cirrhosis and evaluate the potential roles of recombinant human GH (rhGH)
      therapy. Twenty-four patients with HCC with cirrhosis who underwent hepatectomy
      were randomly divided into two groups: a PN group (n = 12) and an rhGH + PN group
      (n = 12). Liver function, serum GH, IGF-1 and IGFBP-3 were measured before the
      operation and at post-operative days (POD) 1 and 6. Insulin-like growth factor-1
      and IGFBP-3 mRNA in the liver tissue was detected by RT-PCR. The liver Ki67
      immunohistochemistry staining was studied. At the same time, 12 patients with
      cholelithiasis or liver hemangioma who underwent operation served as normal
      control group. On POD 6, serum prealbumin, GH, IGF-1, IGFBP-3, hepatic IGF-1
      mRNA, IGFBP-3 mRNA and liver Ki67 LI were higher in the rhGH + PN group than in
      the PN group. There was no significant difference in the 6-and 12-month tumor
      free survival rate and the median tumor-free survival time between the PN group
      and the rhGH + PN group (P>0.05). These data indicate that rhGH + PN could
      ameliorate the changes in the GH/IGF-1 axis after hepatectomy for HCC in the
      setting of cirrhosis. 

PMID- 24573870
TI  - High risk factors for pulmonary fungous infection in intensive care units of
      neurosurgery.
AB  - By analyzing the high risk factors for pulmonary fungous infection in intensive
      care units of neurosurgery, the strategy of early diagnosis and treatment was
      explored. According to the domestic diagnostic standard on pulmonary fungous
      infection, clinical data on 58 patients with the infection in our department were
      analyzed. One hundred and seventeen strains of fungi were separated from the 58
      cases. Candidiasis was the most frequent type, accounting for 92.3% of the cases.
      Conditions such as the severity of primary diseases, long-time coma, long-term
      use of broad-spectrum antibiotic, abuse of glucocorticoid, the open airway, and
      some invasive intubations, may be regarded as high risk factors for pulmonary
      fungous infection. Fluconazole showed good clinical effects on the treatment of
      fungous infection. To eliminate these high risk factors, early diagnosis and the
      use of prophylactic antifungal agents can help reduce the incidence of pulmonary
      fungous infection. 

PMID- 24573869
TI  - Determination of telomerase activity in stem cells and non-stem cells of breast
      cancer.
AB  - Although all normal tissue cells, including stem cells, are genetically
      homologous, variation in gene expression patterns has already determined the
      distinct roles for individual cells in the physiological process due to the
      occurrence of epigenetic modification. This is of special importance for the
      existence of tissue stem cells because they are exclusively immortal within the
      body, capable of self-replicating and differentiating by which tissues renew and
      repair itself and the total tissue cell population maintains a steady-state.
      Impairment of tissue stem cells is usually accompanied by a reduction in cell
      number, slows down the repair process and causes hypofunction. For instance,
      chemotherapy usually leads to depression of bone marrow and hair loss. Cellular
      aging is closely associated with the continuous erosion of the telomere while
      activation of telomerase repairs and maintains telomeres, thus slowing the aging
      process and prolonging cell life. In normal adults, telomerase activation mainly
      presents in tissue stem cells and progenitor cells giving them unlimited growth
      potential. Despite the extensive demonstration of telomerase activation in
      malignancy (> 80%), scientists found that heterogeneity also exists among the
      tumor cells and only minorities of cells, designated as cancer stem cells,
      undergo processes analogous to the self-renewal and differentiation of normal
      stem cells while the rest have limited lifespans. In this study, telomerase
      activity was measured and compared in breast cancer stem cells and non-stem cells
      that were phenotypically sorted by examining surface marker expression. The
      results indicated that cancer stem cells show a higher level of enzyme activity
      than non-stem cells. In addition, associated with the repair of cancer tissue (or
      relapse) after chemotherapy, telomerase activity in stem cells was markedly
      increased. 

PMID- 24573871
TI  - Influence of survivin-targeted siRNA on the biological features of colorectal
      carcinoma cells.
AB  - The transient transfection of survivin-targeted siRNA to Lovo cells and its
      influence on the biological features were studied. Two pairs of 19 base pairs
      (bp) siRNA-specific targeted survivin gene were designed and synthesized by in
      vitro transcription (Survivin-1, Survivin-2). After transient transfection of the
      two survivin-targeted siRNAs to Lovo cells by LipofectamineTM 2000, the
      expression of survivin mRNA was detected by reverse transcription-polymerase
      chain reaction (RT-PCR). Apoptosis was detected by flow cytometry and cell
      proliferation was evaluated by MTT assay. We found that the expression levels of
      survivin mRNA of the two RNAi groups (Survivin-1 group and Survivin-2 group)
      respectively decreased by 70% and 39.1% compared with the control Lovo's. Seventy
      two hours after transfection, apoptosis rates of the two RNAi groups were 21.51%
      and 26.28%, both of which were higher than control Lovo's (9.03%). The results at
      72 h after transfection were that the optical density (OD) at 490 nm of the two
      RNAi groups was 0.581 +/- 0.070 and 0.681 +/- 0.104, both of which were much
      lower than the control Lovo's (2.060 +/- 0.272). Based on the results, we can
      draw a conclusion that the two survivin-targeted siRNAs successfully suppressed
      the expression of survivin mRNA, inhibited cell growth and induce cell apoptosis.
      It provides a powerful evidence for colorectal carcinoma gene therapy. 

PMID- 24573872
TI  - Effect of renal function and hemodialysis on the serum tumor markers in patients
      with chronic kidney disease.
AB  - In patients with chronic renal failure, whether they have had hemodialysis or
      not, the specificity of some of the serum tumor markers for the diagnosis of the
      corresponding tumors is decreased while others remain as valuable as they are in
      patients with normal kidney function. The detection of tumor markers is
      extensively used for the diagnosis of corresponding tumors. It has been recently
      shown that some tumor markers are higher in patients with chronic kidney disease
      (CKD) than in the normal population. The effects of renal function and
      hemodialysis were examined on serum levels of some of the tumor markers including
      CEA, CA199, CA125, AFP, CA153, CA724, CYFRA21-1, NSE, SCC-Ag, PSA, and fPSA. The
      232 non-dialysis patients with CKD and 37 chronic uremic patients treated with
      maintenance hemodialysis were enrolled in this study. The 232 non-dialysis
      patients were divided into three groups according to their Ccr. In group 1, Ccr
      was [Symbol: see text] 25 mL/min. In group 2, Ccr was between 25 and 50 mL/min.
      In group 3, Ccr was [Symbol: see text] 50 mL/min. The male patients were also
      divided into three groups to compare the serum levels of PSA and fPSA among the
      three groups. Nine tumor markers in 37 uremic patients were tested. For
      comparison, 37 non-dialysis patients with similar Ccr of the same age and gender
      served as controls. There existed significant differences in serum levels of CEA,
      CA199, CYFRA21-1, NSE, and SCC-Ag among different Ccr groups and the markers bore
      a negative correlation with Ccr. There were no significant differences among the
      three groups in the serum concentrations of CA125, AFP, CA153, CA724, PSA and
      fPSA. The serum levels of CA125 and NSE were significantly higher (P < 0.01) in
      hemodialysis patients than in the nondialysis control patients. In patients with
      chronic renal failure, who were or were not on hemodialysis, the specificity of
      serum CEA, CA199, CYFRA21-1, NSE, CA125 and SCC-Ag for the diagnosis of the
      corresponding tumors was decreased while serum AFP, CA153, CA724, PSA and fPSA
      were as valuable as they were in patients with normal kidney function.
      Hemodialysis further increased the serum level of CA125 and NSE. 

PMID- 24573873
TI  - Mutation analysis of KCNQ1, KCNH2, SCN5A, KCNE1 and KCNE2 genes in Chinese
      patients with long QT syndrome.
AB  - Long QT syndrome (LQTS) is the prototype of the cardiac ion channelopathies,
      which cause syncope and sudden death. Inherited LQTS is represented by the
      autosomal dominant Romano-ward syndrome (RWS), which is not accompanied by
      congenital deafness, and the autosomal recessive Jervell and Lange-Nielsen
      syndrome (JLNS), which is accompanied by congenital deafness. The LQTS-causing
      mutations have been reported in patients and families from Europe, North America
      and Japan. Few genetic studies have been carried out in families with JLNS from
      China. This study investigates the molecular pathology in four families with LQTS
      (including a family with JLNS) in the Chinese population. Polymerase chain
      reaction and DNA sequencing were used to screen for KCNQ1, KCNH2, KCNE1, KCNE2
      and SCN5A mutation. A missense mutation G314S in an RWS family was identified,
      and a single nucleotide polymorphism (SNP) G643S was indentified in the KCNQ1 of
      the JLNS family. In this JLNS family, another heterozygous novel mutation in exon
      2a was found in KCNQ1 of the patients. Our data provide useful information for
      the identification of polymorphisms and mutations related to LQTS and the Brugada
      Syndrome (BS) in Chinese populations. 

PMID- 24573874
TI  - Abnormal glycosylated hemoglobin as a predictive factor for glucose metabolism
      disorders in antipsychotic treatment.
AB  - The aim of this study was to observe the changes in glucose metabolism after
      antipsychotic (APS) therapy, to note the influencing factors, as well as to
      discuss the relationship between the occurrence of glucose metabolism disorders
      of APS origin and abnormal glycosylated hemoglobin (HbA1c) levels. One hundred
      and fifty-two patients with schizophrenia, whose fasting plasma glucose (FPG) and
      2-h plasma glucose (2hPG) in the oral glucose tolerance test (2HPG) were normal,
      were grouped according to the HbA1c levels, one normal and the other abnormal,
      and were randomly enrolled into risperidone, clozapine and chlorpromazine
      treatment for six weeks. The FPG and 2hPG were measured at the baseline and at
      the end of the study. In the group with abnormal HbA1c and clozapine therapy,
      2HPG was higher after the study [(9.5 +/- 1.8) mmol/L] than that before the study
      [(7.2 +/- 1.4) mmol/L] and the difference was statistically significant (P <
      0.01). FPG had no statistically significant difference before and after the study
      in any group (P > 0.05). HbA1c levels and drugs contributing to 2HPG at the end
      of study had statistical cross-action (P < 0.01). In the abnormal HbA1c group,
      2HPG after the study was higher in the clozapine treatment group [(9.5 +/- 1.8)
      mmol/L] than in the risperidone treatment group [(7.4 +/- 1.7) mmol/L] and the
      chlorpromazine treatment group [(7.3 +/- 1.6) mmol/L]. The differences were
      statistically significant (P < 0.01). In the normal HbA1c group there was no
      statistically significant difference before and after the study in any group (P >
      0.05). 2HPG before [(7.1 +/- 1.6) mmol/L] and after the study [(8.1 +/- 1.9)
      mmol/L] was higher in the abnormal HbA1c group than in the normal HbA1c group
      [(6.2 +/- 1.4) mmol/L vs (6.5 +/- 1.4) mmol/L] with the difference being
      statistically significant (P < 0.01 vs P < 0.001). As compared with normal HbA1c
      group, the relative risk (RR) of glucose metabolism disease occurrence was 4.7 in
      the abnormal HbA1c group with the difference being statistically significant (P <
      0.001). Patients with abnormal HbA1c are more likely to have a higher risk of
      having glucose metabolism disorders after APS treatment. 

PMID- 24573875
TI  - Association of the genetic polymorphism of EPHX1 and EPHX2 with the
      susceptibility to chronic benzene poisoning.
AB  - The aim of this study was to explore the association of the genetic polymorphism
      of EPHX1 and EPHX2 with the susceptibility to chronic benzene poisoning (CBP). A
      case-control study of 268 patients with CBP and 268 healthy workers matched by
      age and sex, all of whom were occupationally exposed to benzene, was conducted.
      The single nucleotide polymorphisms (SNPs, rs2854451, rs3738047, rs2234922 and
      rs1051741) of EPHX1 gene and the SNP (rs751141) of EPHX2 gene were tested by the
      TaqMan PCR method. In the subjects carrying the genotype of EPHX1 rs3738047 GG,
      the risk of CBP was decreased in the individuals simultaneously carrying EPHX1
      rs2234922 G (P = 0.02). Alternatively, in the subjects carrying the genotype of
      EPHX1 rs2234922 AA, the risk of CBP was increased in the individuals
      simultaneously carrying the allele of EPHX2 rs751141A (P = 0.03). It was also
      found that there were potential interactions between alcohol consumption and the
      polymorphism of EPHX1 rs1051741 (chiH (2) = 5.28, P = 0.02) or rs2234922 (chiH
      (2) = 6.71, P = 0.01). Compared to individuals with EPHX1 rs1051741 CC or
      rs2234922 AA genotype in the drinkers, the risk of CBP in those carrying
      genotypes of EPHX1 rs1051741 CT+TT or rs2234922 AG+GG was decreased, respectively
      (P = 0.04, P < 0.01). Haplotype analysis of polymorphisms in EPHX1 showed that
      the risk of CBP was increased in the subjects with haplotype 2 (rs2854451-A,
      rs3738047-G, rs2234922-A, rs1051741-C) or haplotype 4 (rs2854451-G, rs3738047-A,
      rs2234922-G, rs1051741-T), but decreased in those with haplotype 6 (rs2854451-G,
      rs3738047-G, rs2234922-G, rs1051741-T) or haplotype 10 (rs2854451-A, rs3738047-A,
      rs2234922-G, rs1051741-T), respectively. Logistic regression analysis revealed
      that smoking might play a role in modifying the risk of CBP (OR = 0.313, 95% CI:
      0.123-0.794, P = 0.015). The genetic polymorphism in EPHX1 may be associated with
      the risk of CBP in the Chinese occupational population and further research is
      needed for the association between the genetic polymorphism in EPHX2 and the
      susceptibility to CBP. 

PMID- 24573876
TI  - Relationship between reactive oxygen species and sodium-selenite-induced DNA
      damage in HepG2 cells.
AB  - Selenium compounds, as an effective chemopreventive agent, can induce apoptosis
      in tumor cells. Reactive oxygen species (ROS) are important mediators in
      apoptosis induced by various stimuli, which include chemopreventive agents. In
      this study, we investigated the relationship between ROS and the levels of DNA
      damage induced by selenite in HepG2 cells. After HepG2 cells were treated with
      selenite, there was a dose-dependent decrease in cell viability. The levels of
      ROS induced by selenite were measured by 2', 7'-dichlorofluorescein diacetate
      (DCFH-DA) fluorescence, which shos a dose-and time-dependent increase in HepG2
      cells. The levels of DNA damage in HepG2 increased in all cells treated with an
      increasing dose of selenite at 0, 2.5, 5, 10, and 20 MUmol/L. N-acetylcysteine
      (NAC), a known antioxidant, increased cell viability and decreased ROS
      generation. Moreover, NAC effectively blocked DNA damage induced by selenite.
      These results revealed that ROS might play an important role in selenite-induced
      DNA damage that can be reduced by NAC treatment. 

PMID- 24573877
TI  - Synchronous rectal adenocarcinoma and anal canal adenocarcinoma.
AB  - It is difficult to distinguish a rectal carcinoma with anal metastases from
      coexistent synchronous anorectal carcinomas. The therapeutic strategy for rectal
      and anal carcinoma is so different that it should be clearly identified. Here, we
      report on the case of a 63-year-old man who presented with an upper-third rectal
      adenocarcinoma. Five months after resection, he developed an adenocarcinoma in
      the anal canal. The histological slides of both tumors were reviewed and
      immunohistochemical studies for cytokeratins (CKs) 7 and 20 were performed. The
      index tumor demonstrated CK 7-/CK 20+ and the second showed CK7+/CK20+. For this
      reason, we believe the present case had synchronous adenocarcinomas arising from
      anal canal and the rectum separately. It is very important to differentiate the
      anorectal lesions pathologically because of the impact on the therapeutic options
      available, especially for the lesion arising in the anal canal. 

PMID- 24573878
TI  - Sudden death due to arrhythmogenic right ventricular cardiomyopathy: Two case
      reports.
AB  - Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a kind of primary
      myocardial disease characterized by the regional or global replacement of right
      ventricular myocardium by fatty and fibrolipomatous tissues. The ARVC, usually
      presenting with different clinical manifestations and pathological changes, were
      mainly seen in young men and is one of the main causes of sudden death in the
      young. Here two autopsied cases of Chinese men aged 30 and 23 years old who
      appeared healthy but died suddenly while at work are reported respectively. One
      of the victims had extensive and severe pathological changes in his heart
      involving the left ventricular wall as well as the ventricular septum and the
      right atrium. Not only was there a global fatty and fibrolipomatous tissue
      replacement of the right ventricular myocardia, but also mild sarcoplasmic
      coagulation in the myocardium and focal lymphocytic infiltration in the
      myocardial interstitium of the right ventricular wall. In addition, slight
      atherosclerosis of the coronary artery and intimal thickening of the sino-atrial
      node were observed. It is believed that there are no marked differences in the
      pathological changes of ARVC between Chinese patients and patients from western
      countries. The etiology and pathogenesis of ARVC could not be explained by a
      single cause or factor and they are probably related to various congenital and
      acquired causes or factors. 

PMID- 24573879
TI  - NONATObase: a database for Polychaeta (Annelida) from the Southwestern Atlantic
      Ocean.
AB  - Networks can greatly advance data sharing attitudes by providing organized and
      useful data sets on marine biodiversity in a friendly and shared scientific
      environment. NONATObase, the interactive database on polychaetes presented
      herein, will provide new macroecological and taxonomic insights of the
      Southwestern Atlantic region. The database was developed by the NONATO network, a
      team of South American researchers, who integrated available information on
      polychaetes from between 5 degrees N and 80 degrees S in the Atlantic Ocean and
      near the Antarctic. The guiding principle of the database is to keep free and
      open access to data based on partnerships. Its architecture consists of a
      relational database integrated in the MySQL and PHP framework. Its web
      application allows access to the data from three different directions: species
      (qualitative data), abundance (quantitative data) and data set (reference data).
      The database has built-in functionality, such as the filter of data on user
      defined taxonomic levels, characteristics of site, sample, sampler, and mesh size
      used. Considering that there are still many taxonomic issues related to poorly
      known regional fauna, a scientific committee was created to work out consistent
      solutions to current misidentifications and equivocal taxonomy status of some
      species. Expertise from this committee will be incorporated by NONATObase
      continually. The use of quantitative data was possible by standardization of a
      sample unit. All data, maps of distribution and references from a data set or a
      specified query can be visualized and exported to a commonly used data format in
      statistical analysis or reference manager software. The NONATO network has
      initialized with NONATObase, a valuable resource for marine ecologists and
      taxonomists. The database is expected to grow in functionality as it comes in
      useful, particularly regarding the challenges of dealing with molecular genetic
      data and tools to assess the effects of global environment change. Database URL:
      http://nonatobase.ufsc.br/.

PMID- 24573880
TI  - TSLP signaling pathway map: a platform for analysis of TSLP-mediated signaling.
AB  - Thymic stromal lymphopoietin (TSLP) is a four-helix bundle cytokine that plays a
      critical role in the regulation of immune responses and in the differentiation of
      hematopoietic cells. TSLP signals through a heterodimeric receptor complex
      consisting of an interleukin-7 receptor alpha chain and a unique TSLP receptor
      (TSLPR) [also known as cytokine receptor-like factor 2 (CRLF2)]. Cellular targets
      of TSLP include dendritic cells, B cells, mast cells, regulatory T (Treg) cells
      and CD4+ and CD8+ T cells. The TSLP/TSLPR axis can activate multiple signaling
      transduction pathways including the JAK/STAT pathway and the PI-3 kinase pathway.
      Aberrant TSLP/TSLPR signaling has been associated with a variety of human
      diseases including asthma, atopic dermatitis, nasal polyposis, inflammatory bowel
      disease, eosinophilic eosophagitis and, most recently, acute lymphoblastic
      leukemia. A centralized resource of the TSLP signaling pathway cataloging
      signaling events is not yet available. In this study, we present a literature
      annotated resource of reactions in the TSLP signaling pathway. This pathway map
      is publicly available through NetPath (http://www.netpath.org/), an open access
      signal transduction pathway resource developed previously by our group. This map
      includes 236 molecules and 252 reactions that are involved in TSLP/TSLPR
      signaling pathway. We expect that the TSLP signaling pathway map will provide a
      rich resource to study the biology of this important cytokine as well as to
      identify novel therapeutic targets for diseases associated with dysregulated
      TSLP/TSLPR signaling. Database URL:
      http://www.netpath.org/pathways?path_id=NetPath_24. 

PMID- 24573881
TI  - AnaLysis of Expression on human chromosome 21, ALE-HSA21: a pilot integrated web
      resource.
AB  - Transcriptome studies have shown the pervasive nature of transcription,
      demonstrating almost all the genes undergo alternative splicing. Accurately
      annotating all transcripts of a gene is crucial. It is needed to understand the
      impact of mutations on phenotypes, to shed light on genetic and epigenetic
      regulation of mRNAs and more generally to widen our knowledge about cell
      functionality and tissue diversity. RNA-sequencing (RNA-Seq), and the other
      applications of the next-generation sequencing, provides precious data to improve
      annotations' accuracy, simultaneously creating issues related to the variety,
      complexity and the size of produced data. In this 'scenario', the lack of user
      friendly resources, easily accessible to researchers with low skills in
      bioinformatics, makes difficult to retrieve complete information about one or few
      genes without browsing a jungle of databases. Concordantly, the increasing amount
      of data from 'omics' technologies imposes to develop integrated databases merging
      different data formats coming from distinct but complementary sources. In light
      of these considerations, and given the wide interest in studying Down syndrome-a
      genetic condition due to the trisomy of human chromosome 21 (HSA21)-we developed
      an integrated relational database and a web interface, named ALE-HSA21 (AnaLysis
      of Expression on HSA21), accessible at http://bioinfo.na.iac.cnr.it/ALE-HSA21.
      This comprehensive and user-friendly web resource integrates-for all coding and
      noncoding transcripts of chromosome 21-existing gene annotations and transcripts
      identified de novo through RNA-Seq analysis with predictive computational
      analysis of regulatory sequences. Given the role of noncoding RNAs and
      untranslated regions of coding genes in key regulatory mechanisms, ALE-HSA21 is
      also an interesting web-based platform to investigate such processes. The
      'transcript-centric' and easily-accessible nature of ALE-HSA21 makes this
      resource a valuable tool to rapidly retrieve data at the isoform level, rather
      than at gene level, useful to investigate any disease, molecular pathway or cell
      process involving chromosome 21 genes. Database URL:
      http://bioinfo.na.iac.cnr.it/ALE-HSA21/.

PMID- 24573883
TI  - Estimation of body weight in children in the absence of scales: a necessary
      measurement to insure accurate drug dosing.

PMID- 24573882
TI  - COMPARTMENTS: unification and visualization of protein subcellular localization
      evidence.
AB  - Information on protein subcellular localization is important to understand the
      cellular functions of proteins. Currently, such information is manually curated
      from the literature, obtained from high-throughput microscopy-based screens and
      predicted from primary sequence. To get a comprehensive view of the localization
      of a protein, it is thus necessary to consult multiple databases and prediction
      tools. To address this, we present the COMPARTMENTS resource, which integrates
      all sources listed above as well as the results of automatic text mining. The
      resource is automatically kept up to date with source databases, and all
      localization evidence is mapped onto common protein identifiers and Gene Ontology
      terms. We further assign confidence scores to the localization evidence to
      facilitate comparison of different types and sources of evidence. To further
      improve the comparability, we assign confidence scores based on the type and
      source of the localization evidence. Finally, we visualize the unified
      localization evidence for a protein on a schematic cell to provide a simple
      overview. Database URL: http://compartments.jensenlab.org. 

PMID- 24573884
TI  - Lost among the trees? The autonomic nervous system and paediatrics.
AB  - The autonomic nervous system (ANS) has been strikingly neglected in Western
      medicine. Despite its profound importance for regulation, adjustment and
      coordination of body systems, it lacks priority in training and practice and
      receives scant attention in numerous major textbooks. The ANS is integral to
      manifestations of illness, underlying familiar physical and psychological
      symptoms. When ANS activity is itself dysfunctional, usual indicators of acute
      illness may prove deceptive. Recognising the relevance of the ANS can involve
      seeing the familiar through fresh eyes, challenging assumptions in clinical
      assessment and in approaches to practice. Its importance extends from physical
      and psychological well-being to parenting and safeguarding, public services and
      the functioning of society. Exploration of its role in conditions ranging from
      neurological, gastrointestinal and connective tissue disorders, diabetes and
      chronic fatigue syndrome, to autism, behavioural and mental health difficulties
      may open therapeutic avenues. The ANS offers a mechanism for so-called functional
      illnesses and illustrates the importance of recognising that 'stress' takes many
      forms, physical, psychological and environmental, desirable and otherwise.
      Evidence of intrauterine and post-natal programming of ANS reactivity suggests
      that neonatal care and safeguarding practice may offer preventive opportunity, as
      may greater understanding of epigenetic change of ANS activity through, for
      example, accidental or psychological trauma or infection. The aim of this article
      is to accelerate recognition of the importance of the ANS throughout paediatrics,
      and of the potential physical and psychological cost of neglecting it. 

PMID- 24573885
TI  - Down-regulated Six2 by knockdown of neurofibromin results in apoptosis of
      metanephric mesenchyme cells in vitro.
AB  - Embryonic Six2-positive nephron progenitor cells adjacent to ureteric bud tips
      ultimately give rise to nephron structures, including proximal and distal
      tubules, podocytes, Bowman's capsules, and the glomeruli. This process requires
      an internal balance between self-renew and differentiation of the nephron
      progenitor cells, which is mediated by numerous molecules. Recent studies have
      shown that the neurofibromin (Nf1) null mutant mouse embryos have an 18- to 24-h
      developmental delay in metanephros manifesting retardation in its cephalad
      repositioning and reduction number of glomeruli. However, the underlying inter
      /intracellular signaling mechanisms responsible for reducing number of glomeruli
      during nephrogenesis remain to be fully elucidated. Here, we originally detected
      the Nf1 expression in developing kidney and metanephric mesenchyme cells.
      Surprisingly, Nf1 knockdown by small interfering RNAs in the metanephric
      mesenchyme cells (mK3) resulted in a decreased expression of Six2, the key marker
      of renal progenitor cells, while the ratio of apoptotic cells was significantly
      increased. Furthermore, overexpression of Six2 in mk3 cells partially rescued
      apoptosis phenotype. Collectively, these results implied that knockdown of Nf1
      resulted in apoptosis of mK3 cells in vitro probably through down-regulation of
      Six2 expression. Collectively, we demonstrated that down-regulated Six2 by
      knockdown of Nf1 resulted in apoptosis of mK3 cells in vitro. These results
      implied that inhibition of Nf1 may delay metanephros development via down
      regulation of Six2.

PMID- 24573888
TI  - Posterior approach for low cervical fractures with unilateral or bilateral facet
      dislocation.
AB  - We evaluated treatment by posterior approach and its results for unilateral and
      bilateral facet dislocation of the lower cervical spine. Fracture reduction and
      ultimate stabilization of low cervical fractures located between C3 and C7 depend
      on the mechanism of the lesion and the resulting affectation of the
      osteoligamentary structures. The varied surgical approaches to fractures with
      unilateral or bilateral luxation include anterior, posterior, and combined. No
      surgery is performed if a conservative approach is used. Of the 71 low cervical
      fractures treated in our service in 10 years, 42 were facetary luxations
      (unilateral in 24 patients and bilateral in 18). Radiological studies included X
      ray, CT and, in some cases, MRI. Once cervical fracture was diagnosed, halo
      traction was initiated and the decision to operate (34 cases) or continue
      conservative treatment (eight cases) was made a week after admittance. Surgery
      consisted of the posterior approach (27 bilateral clamps with bone graft, 5 wires
      with bone graft, and two posterior plates). Average patient follow-up was 7
      (range 2-12) years. The patients' neurological status improved in 30 cases
      (71.42%) and was unchanged in 12 (28.57%). Three of eight patients initially
      treated conservatively developed radicular pain and instability and underwent
      surgery. Clamps were placed via a posterior approach in one case and the other
      two cases required a combined posterior and anterior approach. No instrumentation
      has required removal, although one patient developed a wall abscess. We found a
      posterior approach provides good stability for placing an arthrodesis in patients
      with a unilateral or bilateral cervical dislocation. In most of our cases we used
      clamps, and there was no worsening of any patient's neurological condition. 

PMID- 24573886
TI  - Genistein induces apoptosis and autophagy in human breast MCF-7 cells by
      modulating the expression of proapoptotic factors and oxidative stress enzymes.
AB  - Breast cancer is one of the common tumors occurring in woman and despite
      treatment, the prognostic is poor. Genistein, a soy isoflavone, has been reported
      to have chemopreventive?chemotherapeutic potential in multiple tumor types. Here,
      we investigated the genistein antiproliferative effect in MCF-7 breast cancer,
      underlying the molecular mechanisms involved in this effect. MCF-7 cancer and
      CCD1059sK fibroblast cells were treated with estradiol (10 nM) or genistein (0.01
      100 MUM) for 24, 48, and 72 h and the cell proliferation was investigated by MTT;
      membrane cell permeability was evaluated by LDH and PI incorporation; apoptosis
      was investigated by externalization of phosphatidylserine by FACS; and presence
      of autophagy was detected by LC3A/B immunostaining. The expression of apoptotic
      proteins and antioxidant enzymes was evaluated by qPCR. The results demonstrate
      that genistein (100 MUM) for 72 h of treatment selectively reduced MCF-7 cell
      proliferation independent of estrogen receptor activation, while no cytotoxicity
      was observed in fibroblast cells. Further experiments showed that genistein
      induced phosphatidylserine externalization and LC3A/B immunopositivity in MCF-7
      cells, indicating apoptosis and autophagy cell death. Genistein increased in
      three times proapoptotic BAX/Bcl-2 ratio and promoted a parallel downregulation
      of 20 times of antiapoptotic survivin. In addition, genistein promoted a decrease
      of 5.5, 9.3, and 3.6 times of MnSOD, CuZnSOD, and TrxR mRNA expression,
      respectively, while the GPx expression was increased by 6.5 times. These results
      suggest that the antitumor effect of genistein involved the modulation of
      antioxidant enzyme and apoptotic signaling expression, which resulted in
      apoptosis and progression of autophagy.

PMID- 24573887
TI  - The role of TGFbeta1 stimulating ROCK I signal pathway to reorganize actin in a
      rat experimental model of developmental dysplasia of the hip.
AB  - Importance of actin organization in control of chondrocyte phenotype is well
      established, but little is known about the role of transforming growth factor
      beta1 (TFGbeta1) in regulating of ROCK I signal pathway. Here, we investigated
      the role of the TGFbeta1, a well-studied member of the TGF-beta superfamily, in
      chondrogenesis. Newborn Rats were randomly assigned to developmental dysplasia of
      the hip (DDH) group and control group. The isolated hips were performed with HE
      staining and immunohistochemistry. The chondrocytes was isolated and stained by
      immunofluorescence. The relative quantification of TGFbeta1 on mRNA level was
      determined using real-time RT-PCR, and its secretion in culture supernatant in
      each well was detected by means of ELISA. The expression of ROCK I and ROCK II
      was detected by means of Western Blot. The relative amounts of actin in detergent
      soluble and insoluble fractions were determined. Furthermore, TGFbeta1 were
      employed to stimulate normal primary culture chondrocytes in vitro. We found
      TFGbeta1 significantly changed in acetabulum chondrocytes after mechanical
      overloading. Over expression of TFGbeta1 was observed by means of RT-PCR and
      ELISA assay. The expression of ROCK I was significantly increased in DDH
      acetabulum chondrocytes compared with normal cells. The detergent-soluble actin
      was confirmed reorganization in DDH chondrocytes. Furthermore, TFGbeta1 can
      stimulate the ROCK I signaling to modulate actin location in vitro. In
      conclusion, our data suggested that TFGbeta1 expression suppresses chondrogenesis
      through the control of ROCK signaling and actin organization. 

PMID- 24573889
TI  - Internal fixation of lateral clavicle fractures with Vicryl tape.
AB  - Six consecutive Neer type II fractures of the lateral end of the clavicle were
      treated by indirect open reduction and internal fixation using Vicryl tape. All
      fractures healed within 6-8 weeks after the operation. The pre-injury level of
      function was restored in all cases. This method of fixation is relatively simple
      and appears to be a valuable alternative to Bosworth-type screw fixation. 

PMID- 24573890
TI  - Segmental femoral cement extraction at revision hip arthroplasty - a safe
      technique.
AB  - Conventional methods of femoral cement extraction at revision hip arthroplasty
      may be associated with incomplete cement removal, excessive sacrifice of
      cancellous bone stock, inadvertent cortical perforation, or fracture. Segmental
      femoral cement extraction is a technique, first introduced in the early 1990s to
      optimise cement removal while minimising the potential complications of this
      procedure. It involves the instilling of fresh polymethylmethacrylate (PMMA) into
      the carefully prepared cement mantle after implant removal. Segments of new
      cement bound to the old mantle are then extracted. Since its initial description,
      few subsequent series have been published to validate or discredit this
      technique. We report on 25 consecutive femoral revisions employing this system.
      Complete cement removal was achieved in 88%. The integrity of the femoral cortex
      was preserved in all cases with no perforations or fractures. 

PMID- 24573891
TI  - Dall-Miles cable and plate system for periprosthetic femoral fracture.
AB  - Management of femoral shaft fractures in association with hip implants in situ is
      a difficult and complex problem. We present here our experience of nine
      periprosthetic femoral fractures treated successfully with open reduction and
      internal fixation using the Dall-Miles plate and cable system. We recommend this
      system for fixation of the type 3 fractures using a minimum of three proximal
      cables and three distal cables with supplementary screws. 

PMID- 24573892
TI  - Elevated prostate specific antigen (PSA) levels a risk factor for pathological
      hip fracture in metastatic prostatic carcinoma.
AB  - Metastatic carcinoma of the prostate is increasing in incidence and commonly
      affects the proximal femur, but fracture risk is difficult to predict.
      Prophylactic fixation may avert the technical problems and reduce post-operative
      complications associated with acute pathological fracture treatment. This is a
      retrospective study of 14 patients who sustained a pathological fracture in the
      proximal femur from prostatic metastases. Risk factors for fracture were
      assessed, peri-operative complications highlighted and patient survival noted. At
      time of the initial diagnosis of prostate carcinoma, 12/14 patients (86%) had
      uptake in the proximal femur on isotope bone scan and 11/14 (79%) had an initial
      prostate specific antigen (PSA) level above 100 ng/ml. A higher initial PSA level
      correlated with a shorter time to fracture. The subtrochanteric region was the
      most common fracture location and was technically the most demanding to fix.
      Blood loss and transfusion requirements were high. Post-operative survival was
      71%, 50% and 36% at 6, 12 and 18 months, respectively. From our findings, we
      suggest that patients with a greatly elevated PSA (>100 ng/ml), a positive
      isotope bone scan and plain X-ray changes in the proximal femur are at high risk
      of fracture and should be referred early for prophylactic stabilisation. 

PMID- 24573893
TI  - Polylactide acid pins versus stainless steel pins in the treatment of diaphyseal
      fracture: Experimental study in rats.
AB  - In order to develop a biodegradable pin for diaphyseal femoral fracture fixation,
      polylactide acid (PLA) pins were implanted in the femoral bone of rats. A distal
      diaphyseal fracture was performed. Union and tissue reaction to PLA pins versus
      stainless steel pins was studied after 15 days, and 1, 2 and 6 months of
      implantation. PLA and stainless steel pins induced the same union and a similar
      tissue reaction during the 6-month period. Biocompatibility of material was
      satisfactory. 

PMID- 24573894
TI  - Boyd H.B. and Griffin L.L. classification: A refinement proposal.
AB  - The purpose of this review is to describe a more precise type II classification
      of Boyd and Griffin (1949). It seems possible, according to the different
      intertrochanteric fractures, to describe three sub-groups. Classification takes
      account the most recent description of the coronal plane fracture (Briot 1980)
      and the behaviour of the compressed cancellous bone (Ender 1970). It allows a
      better understanding of what is called an unstable hip fracture and a better
      physiological approach. 

PMID- 24573895
TI  - Unusual variation of the extensor digitorum brevis manus: A case report.
AB  - An anomalous muscle, the extensor digitorum brevis manus (EDBM) was found at the
      dorsum of the right hand arising from the wrist capsule beneath the extensor
      retinaculum and inserting into the ulnar side of the basis of the proximal
      phalanx of the long finger. The EDBM was located superficial to the common
      extensor tendons of the fingers. We analyze the tendency of the dominant hand to
      be involved and the possible complications such as the appearance of the "fourth
      compartment syndrome" or attrition ruptures of the common extensor tendons. We
      report the various applications of the EDBM in surgery, such as its use as a flap
      in covering defects of the distal tibia. Finally, we present the different
      theories about the development of the EDBM and the treatment in symptomatic cases
      with division of the extensor retinaculum or complete surgical excision of the
      muscle. 

PMID- 24573897
TI  - Concerns: Article of J.F. Quinlan, D. McCarthy and W.R. Quinlan.

PMID- 24573896
TI  - Low-velocity dislocations of knee joint.
AB  - We treated two cases of low-velocity traumatic total dislocations of the knee
      joint. Although the injuries were similar, management was different due to a
      difference in ages and functional demands of the individual patients. In the
      first patient, with low functional demands, non-operative treatment of ligament
      injuries resulted in a functional knee. However, in the second young and active
      patient, optimal functional outcome was achieved with surgical repair of knee. 

PMID- 24573898
TI  - Multiple myeloma and intramedullary nailing.

PMID- 24573899
TI  - Recent CD-ROM releases.

PMID- 24573900
TI  - Assemblee Generale de la S.O.T.EST.

PMID- 24573901
TI  - Space-time prospective surveillance based on Knox local statistics.
AB  - We studied a surveillance system to prospectively monitor the emergence of space
      time clusters in point pattern of disease events. Its aim is to detect a cluster
      as soon as possible after its emergence, and it is also desired to keep the rate
      of false alarms at a controlled level. The method is a modification from a
      previous proposal based on a local version of the Knox statistic and which
      examined a retrospective surveillance scenario, looking for the earliest time in
      the past that change could have been deemed to occur. We modify this method to
      take into account the prospective case, being able then to fix the serious
      difficulties found by other authors. We evaluated the surveillance system in
      several scenarios, including without and with emerging clusters, checking
      distributional assumptions, and assessing performance impacts of different
      emergence times, shapes, extent, and intensity of the emerging clusters. Our
      conclusion is that the space-time surveillance system based on local Knox
      statistics is very efficient in its statistical properties, and it is appealing
      to epidemiologists and public health officials because it is simple to use and
      easily understandable. This makes it a promising candidate to practical use by
      public health official agencies.

PMID- 24573904
TI  - Association between the bladder wall thickness and urodynamic findings in
      patients with spinal cord injury.
AB  - PURPOSE: To investigate whether ultrasonographic bladder wall thickness (BWT)
      correlates with urodynamic parameters in patients with spinal cord injury (SCI).
      METHODS: Two hundred and seventy-two patients with SCI were enrolled in the
      study. All of the patients underwent bladder ultrasonography and urodynamic
      study. The anterior bladder wall was measured and compared to urodynamic data.
      RESULTS: The mean age of the patients was 37.4 years. The mean BWT was 3.9 mm.
      BWT was significantly higher in the patients with neurogenic detrusor
      overactivity associated with detrusor sphincter dyssynergia (NDO/DSD) compared to
      those without sphincter dyssynergia (4.2 vs. 3.6 mm, respectively, p < 0.001) and
      in those with compliance <20 ml/cm H2O. Nevertheless, ROC curve analysis [ROC =
      0.624, 95 % CI (0.530, 0.718), p = 0.011] showed that no meaningful BWT
      measurement cutoff could be made to predict an elevated detrusor pressure in the
      storage phase. CONCLUSIONS: Increased BWT was present in patients with low
      bladder compliance and NDO/DSD. No BWT cutoff value to predict an elevated
      detrusor pressure was found. Therefore, the measurement of BWT has no clinical
      role in patients with SCI and cannot replace urodynamic evaluation.

PMID- 24573905
TI  - Effect of stereochemistry of avermectin-like 6,6-spiroketals on biological
      activities and endogenous biotransformations in Streptomyces avermectinius.
AB  - Natural avermectins (AVEs) share a 6,6-spiroketal moiety with an exclusive R
      configuration at the C21 spirocyclic junction. Herein, we report the
      characterization of nine AVE-like spiroketals of two types (C21 S and R) in a
      mutant strain that lacks spirocyclase activity. Comparative analysis of their
      structures facilitated evaluation of the effect of stereochemistry on endogenous
      biotransformations and biological activities of the spiroketals. 

PMID- 24573907
TI  - Interactions between freons: a rotational study of CH2F2-CH2Cl2.
AB  - The rotational spectra of two isotopologues of a 1:1 difluoromethane
      dichloromethane complex have been investigated by pulsed-jet Fourier-transform
      microwave spectroscopy. The assigned (most stable) isomer has C(s) symmetry and
      it displays a network of two C-H???Cl-C and one C-H???F-C weak hydrogen bonds,
      thus suggesting that the former interactions are stronger. The hyperfine
      structures owing to (35)Cl (or (37)Cl) quadrupolar effects have been fully
      resolved, thus leading to an accurate determination of the three diagonal
      (chi(gg); g=a, b, c) and the three mixed quadrupole coupling constants (chi(gg');
      g, g'=a, b, c; g?g'). Information on the structural parameters of the hydrogen
      bonds has been obtained. The dissociation energy of the complex has been
      estimated to be 7.6 kJ mol(-1).

PMID- 24573908
TI  - Direct evidence for structural transition promoting shear thinning in cylindrical
      colloid assemblies.
AB  - In this paper, we describe stimuli-responsive hydrogels prepared from a rigid rod
      like polyelectrolyte 'imogolite' and a dicarboxylic acid. The hydrogel exhibited
      thixotropy in response to mechanical shock within the order of seconds or sub
      seconds. Here, using the latest structural/rheological characterisation
      techniques, the relationship between the structural transition processes and the
      shear thinning was estimated. The evidence obtained by the experiments revealed
      for the first time the direct relationship between the microscopic structural
      change and the macroscopic thixotropic behavior that have been extensively
      discussed. The thixotropic hydrogel has the hierarchical architecture in the
      combination of imogolite and dicarboxylic acid, i.e., sheathed
      nanotubes/hydroclusters of cross-bridged nanotubes/frameworks. The formation and
      disintegration of the network structure upon resting and agitating, respectively,
      were the origin of gel/sol transition (thixotropy), although the hydroclusters of
      cross-bridged nanotubes were maintained throughout the transition. 

PMID- 24573903
TI  - Absence of C9ORF72 expanded or intermediate repeats in autopsy-confirmed
      Parkinson's disease.
AB  - BACKGROUND: We have reported that intermediate repeat lengths of the C9ORF72
      repeat are a risk factor for Parkinson's disease (PD) in a clinically diagnosed
      data set. Because 10% to 25% of clinically diagnosed PD have different diagnoses
      upon autopsy, we hypothesized that this may reflect phenotypic heterogeneity or
      concomitant pathology of other neurodegenerative disorders. METHODS: We screened
      488 autopsy-confirmed PD cases for expansion haplotype tag rs3849942T. In 196
      identified haplotype carriers, the C9ORF72 repeat was genotyped using the repeat
      primed polymerase chain reaction assay. RESULTS: No larger (intermediate or
      expanded) repeats were found in these autopsy-confirmed PD samples. This absence
      of larger repeats is significantly different from the frequency in clinically
      diagnosed datasets (P = 0.002). CONCLUSIONS: Our results suggest that expanded or
      intermediate C9ORF72 repeats in clinically diagnosed PD or parkinsonism might be
      an indication of heterogeneity in clinically diagnosed PD cases. Further studies
      are needed to elucidate the potential contribution of the C9ORF72 repeat to
      autopsy-confirmed PD.

PMID- 24573910
TI  - [A 15-year-old adolescent presenting both Madelung deformity with Vickers'
      ligament and additional palmaris profundus muscle].
AB  - The palmaris profundus muscle is a rare entity which has been mentioned in
      association with nerve compressions. Madelung deformity is based both on an
      osteochondral lesion of the distal radial physis and often on the Vickers'
      ligament which originates around the lunate and inserts proximally in the radial
      physis. A 15-year-old right-handed female adolescent suffered from symptomatic
      left-sided Madelung deformity with Vickers' ligament and additional palmaris
      profundus muscle. 

PMID- 24573909
TI  - Does electronic monitoring influence adherence to medication? Randomized
      controlled trial of measurement reactivity.
AB  - BACKGROUND: Electronic monitoring is recommended for accurate measurement of
      medication adherence but a possible limitation is that it may influence
      adherence. PURPOSE: To test the reactive effect of electronic monitoring in a
      randomized controlled trial. METHODS: A total of 226 adults with type 2 diabetes
      and HbA1c >=58 mmol/mol were randomized to receiving their main oral glucose
      lowering medication in electronic containers or standard packaging. The primary
      outcomes were self-reported adherence measured with the MARS (Medication
      Adherence Report Scale; range 5-25) and HbA1c at 8 weeks. RESULTS: Non
      significantly higher adherence and lower HbA1c were observed in the electronic
      container group (differences in means, adjusting for baseline value: MARS, 0.4
      [95 % CI -0.1 to 0.8, p = 0.11]; HbA1c (mmol/mol), -1.02 [-2.73 to 0.71, p =
      0.25]). CONCLUSIONS: Electronic containers may lead to a small increase in
      adherence but this potential limitation is outweighed by their advantages. Our
      findings support electronic monitoring as the method of choice in research on
      medication adherence. (Trial registration Current Controlled Trials ISRCT
      N30522359).

PMID- 24573912
TI  - Direct medical costs for complications among children and adults with diabetes in
      the US commercial payer setting.
AB  - BACKGROUND: Complications associated with diabetes are a major contributor to the
      burden of the disease. To better inform decision modelling, there is a need for
      cost estimates of specific diabetes-related complications, stratified by diabetes
      type and patient age group. OBJECTIVE: To obtain direct medical costs of managing
      and treating diabetes-related complications over a 2-year period, for adults and
      children with type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM),
      using data from a large commercially insured US subscriber database. METHODS: We
      examined records from a large US multi-payer claims database to identify patients
      with any diabetes-related complications included in nine pre-specified
      categories, filed between January 2009 and September 2010, and with pre-index
      evidence of T1DM or T2DM. Patients were required to have continuous health plan
      enrolment 12 months before and 24 months after each index complication. Patients
      were classified into cohorts based on their diabetes type and age status at the
      time of the complication. The direct medical cost associated with each
      complication was calculated for the 12- and 24-month follow-up periods. Mean paid
      and allowed total costs were calculated and inflation-adjusted to the year 2011.
      RESULTS: Of the 119,715 patients who met the inclusion criteria, 211 (0.2 %) were
      categorized as children with T1DM, 55 (0.05 %) as children with T2DM, 6,227 (5.2
      %) as adults with T1DM and 113,222 (94.6 %) as adults with T2DM. The respective
      mean cohort ages were 13.5, 14.9, 48.5 and 58 years. Proteinuria/albuminuria was
      the most common complication for T1DM and T2DM child cohorts, with this
      complication occurring in almost one third of these children. Among the child
      cohorts, renal disease accounted for the highest mean paid cost for T1DM patients
      (US$6,053) whereas for T2DM patients, the complication associated with the
      highest mean paid cost was lactic acidosis (US$25,053). For the adult T1DM
      cohort, the complications with the highest occurrence and highest mean total paid
      cost were non-proliferative retinopathy (40.3 %) and renal disease (US$28,076),
      respectively. Similarly, for the adult T2DM cohort, these complications were
      neuropathy (26.8 %) and peritoneal dialysis (US$32,826). CONCLUSION: With the
      continuing and increasing interest in child and adult T1DM and T2DM, stakeholders
      will need relevant and timely information to guide treatment decision making.
      This cost research may directly inform the economic models that are often
      developed to better identify, understand and manage key economic considerations
      that drive the costs of this chronic disease.

PMID- 24573911
TI  - Impact of early versus late systemic lupus erythematosus diagnosis on clinical
      and economic outcomes.
AB  - BACKGROUND AND OBJECTIVES: Systemic lupus erythematosus (SLE) is a multisystem
      complex autoimmune disease that often mimics symptoms of other illnesses, which
      complicates the ability of healthcare providers to make the diagnosis. The
      objective of this study was to assess clinical outcomes, resource utilization,
      and costs between patients with earlier versus later SLE diagnosis. METHODS:
      Patients aged 18-64 years were identified from a large US commercial claims
      database between January 2000 and June 2010. Confirmed SLE diagnosis with a
      claims-based algorithm required either three or more claims for a visit to a
      rheumatologist on separate dates with an SLE diagnosis (International
      Classification of Diseases [ICD-9] code 710.0x), two or more claims for visits to
      a rheumatologist at least 60 days apart with SLE diagnoses, or two or more claims
      for visits to rheumatologist less than 60 days apart with SLE diagnoses with at
      least one dispensing for a typical SLE medication. SLE probable onset date was
      identified during the 12-month baseline period by the second claim for
      antinuclear antibody tests or prodromal symptoms of SLE. Patients were stratified
      into early or late diagnosis groups based on time between probable SLE onset and
      diagnosis (<6 months or >=6 months, respectively). Each patient observation
      period began on the date of the first medical claim, with a diagnosis code for
      SLE that satisfied the inclusion criteria, and ended on the earliest date between
      health plan disenrollment and 30 June 2010. Patients in each group were
      propensity-score matched on age, gender, diagnosis year, region, health plan
      type, and comorbidities. Flare rates and resource utilization were compared post
      diagnosis between groups using rate ratios. All-cause and SLE-related costs
      (adjusted to 2010 US dollars) per patient per month (PPPM) were calculated.
      RESULTS: There were 4,166 matched patients per group. Post-SLE diagnosis, the
      early diagnosis group had lower rates of mild (rate ratio [RR] 0.95; 95 % CI 0.93
      0.96), moderate (RR 0.96; 95 % CI 0.94-0.99), and severe (RR 0.87; 95 % CI 0.82
      0.93) flares compared with the late diagnosis group. The rates of
      hospitalizations (RR 0.80; 95 % CI 0.75-0.85) were lower for the early diagnosis
      group than the late diagnosis group. Compared with late diagnosis patients, mean
      all-cause inpatient costs PPPM were lower for the early diagnosis patients
      (US$406 vs. US$486; p = 0.016). Corresponding SLE-related hospitalization costs
      were also lower for early compared with late diagnosis patients (US$71 vs. US$95;
      p = 0.013). Results were consistent for other resource use and cost categories.
      CONCLUSIONS: Patients diagnosed with SLE sooner may experience lower flare rates,
      less healthcare utilization, and lower costs from a commercially insured
      population perspective. This finding needs to be further explored within the
      context of background SLE disease activity.

PMID- 24573915
TI  - Photocontrol over self-assembled nanostructures of pi-pi stacked dyes supported
      by the parallel conformer of diarylethene.
AB  - Diarylethenes (DAEs) have rarely been used in the design of photoresponsive
      supramolecular assemblies with a well-defined morphology transition owing to
      rather small structural changes upon photoisomerization. A supramolecular design
      based on the parallel conformation of DAEs enables the construction of
      photoresponsive dye assemblies that undergo remarkable nanomorphology
      transitions. The cooperative stacking of perylene bisimide (PBI) dyes was used to
      stabilize the parallel conformer of DAE through complementary hydrogen bonds.
      Atomic force microscopy, UV/Vis spectroscopy, and molecular modeling revealed
      that our DAE and PBI building blocks coassembled in nonpolar solvent to form well
      defined helical nanofibers featuring J-type dimers of PBI dyes. Upon irradiating
      the coassembly solution with UV and visible light in turn, a reversible
      morphology change between nanofibers and nanoparticles was observed. This system
      involves the generation of a new self-assembly pathway by means of photocontrol. 

PMID- 24573916
TI  - Catalytic asymmetric Tamura cycloadditions.
AB  - In the presence of a novel, tert-butyl-substituted squaramide-based catalyst,
      enolizable anhydrides react with alkylidene oxindoles to generate spirooxindole
      products of significant synthetic interest with excellent enantio- and
      diastereocontrol. The methodology is of wide scope and encompasses both
      homophthalic and glutaconic anhydride derivatives, which lead to structurally
      diverse products. Glutaconic acid-derived anhydrides undergo a clean post
      cyclization decarboxylation process which is not a feature of reactions involving
      homophthalic acid-derived anhydrides. The unusual influence of reaction
      temperature on diastereocontrol has been probed, with reactions occurring at 30 
      degrees C and -30  degrees C delivering products epimeric at one stereocenter
      only, in near optical purity. 

PMID- 24573917
TI  - The assessment of the relationship between various waterscapes and outdoor
      activities: Edirne, Turkey.
AB  - The environment is very important in terms of the behaviours and actions of human
      beings, and activity-environment correlation is used frequently in outdoor
      arrangements. The environment must meet the requirements and expectations of
      society. Outdoor activities are the activities that contribute to the well-being
      of human beings in physical (heartbeat, respiration, blood pressure, etc.)
      (Ulrich, Journal of Environmental Psychology 11:210-230, 1991), psychological
      (fear, anxiety, depression, loneliness, stress, etc.) (Marcus and Barnes 1999)
      and behavioural (insomnia, nervousness, restlessness, passivity, etc.) (Ulrich
      1999) terms. It is known that human beings are affected significantly by the
      environments they are in, and more importantly, it is known that the environment
      they are in affects their happiness status. The causes of this effect are the
      features and appearances of the spatial elements and components that mainly make
      up such environments. One of the elements that is used frequently in landscape is
      water. If one examines designed or natural open spaces, it may be observed that
      water has very distinctive features. Dynamic (in the form of a leak, with intense
      flow rate, cascade, foamy, squirting, jet, graded, etc.) and still water elements
      may be used with sculptures, plants, rocks and elevations (on land). This study
      aims to reveal which age groups of students enjoy the different types of
      activities with regards to water features and emotional associations that motion
      and characteristics of water bring out in human beings and also to reveal the
      water preferences of human beings, including their reasons for such preference.
      Thus, 20 different water compositions located in Edirne Province were selected,
      and in 2-min camera reels, the students of various age groups assessed water with
      various characteristic features via a survey. As a result, it was revealed that
      human beings from various age groups wish to perform different activities with
      water elements having distinctive characteristic features, and the types of water
      elements that are subject to various age groups' like and dislike were
      determined. Kruskal-Wallis test was used during testing the effect of age
      differences. Chi-square analysis was used in order to examine the effect of age
      differences on preferences with regards to the activities that shall be performed
      at locations that include utilization of various water elements. The results
      reveal that while the use of water should be allowed in landscaping, selections
      regarding the elements of these water features should be made based on the type
      of activity and the age group of users in relation to the location.

PMID- 24573918
TI  - Use of leaf litter breakdown and macroinvertebrates to evaluate gradient of
      recovery in an acid mine impacted stream remediated with an active alkaline
      doser.
AB  - The spatial congruence of chemical and biological recovery along an 18-km acid
      mine impaired stream was examined to evaluate the efficacy of treatment with an
      alkaline doser. Two methods were used to evaluate biological recovery: the
      biological structure of the benthic macroinvertebrate community and several
      ecosystem processing measures (leaf litter breakdown, microbial respiration
      rates) along the gradient of improved water chemistry. We found that the doser
      successfully reduced the acidity and lowered dissolved metals (Al, Fe, and Mn),
      but downstream improvements were not linear. Water chemistry was more variable,
      and precipitated metals were elevated in a 3-5-km "mixing zone" immediately
      downstream of the doser, then stabilized into a "recovery zone" 10-18 km below
      the doser. Macroinvertebrate communities exhibited a longitudinal pattern of
      recovery, but it did not exactly match the water chemistry gradient Taxonomic
      richness (number of families) recovered about 6.5 km downstream of the doser,
      while total abundance and % EPT taxa recovery were incomplete except at the most
      downstream site, 18 km away. The functional measures of ecosystem processes (leaf
      litter breakdown, microbial respiration of conditioned leaves, and shredder
      biomass) closely matched the measures of community structure and also showed a
      more modest longitudinal trend of biological recovery than expected based on pH
      and alkalinity. The measures of microbial respiration had added diagnostic value
      and indicated that biological recovery downstream of the doser is limited by
      factors other than habitat and acidity/alkalinity, perhaps episodes of AMD and/or
      impaired energy/nutrient inputs. A better understanding of the factors that
      govern spatial and temporal variations in acid mine contaminants, especially
      episodic events, will improve our ability to predict biological recovery after
      remediation. 

PMID- 24573919
TI  - Salivary estradiol and testosterone in Filipino men: Diurnal patterns and
      relationships with adiposity.
AB  - OBJECTIVES: We used detailed saliva sampling procedures to test for diurnal
      changes in men's salivary estradiol (E2) and testosterone (T) and assessed
      whether greater adiposity predicted higher E2 and T. METHODS: We drew on a
      subsample of young adults enrolled in a long-running birth cohort study in Metro
      Cebu, Philippines. Subjects provided saliva samples at four time points during
      the day (waking, waking +40 min, early evening, and bedtime), which were assayed
      for E2 and T. Using these detailed hormonal data, we calculated E2 (n = 29) and T
      (n = 44) area-under-the-curve values, which provide insights on hormonal
      production over the study period. RESULTS: While T declined immediately after
      waking and reached a nadir in the early evening, E2 did not show significant
      diurnal change (P >= 0.1) but was positively correlated to T at multiple time
      points (P <= 0.05). Subjects with higher adiposity (BMI, waist circumference,
      skinfolds) had elevated E2 secretion throughout the day (P <= 0.01), but
      adiposity was not related to salivary T. CONCLUSIONS: Consistent with past
      research, our results indicate that adipose tissue is a significant site of E2
      production in males but differ from a limited number of prior studies of young
      men in that we did not find lower T with increasing adiposity. Given E2's role in
      male hypothalamic-pituitary-gonadal function and complex interfaces with the
      immune system, these results have important implications for models of male life
      history as rates of overweight and obesity rise in populations around the world.

PMID- 24573920
TI  - An investigation of the stability of emerging new psychoactive substances.
AB  - The evolving nature of new psychoactive substances (NPS) - often referred to as
      'legal highs', 'designer drugs' or 'bath salts' - presents an evolving challenge
      for toxicologists. Apart from the detection and identification of these
      compounds, further analytical challenges may arise from the presence of possible
      metabolites or degradation products which may have to be considered when devising
      an analytical strategy. Whilst there has been some stability research for some
      more established drugs of abuse and medicinal products, data on emerging NPS are
      less abundant. In order to address this need, 13 NPS (4-MEC, MDAI, methoxetamine,
      5-MeO-DALT, 6-APB, MPA, 5-IAI, MDAT, 2-AI, AMT, 25C-NBOMe, AH-7921, 5-MAPB) were
      spiked in blood and plasma and kept at room temperature (20-23  degrees C).
      Detection and identification of the suspected breakdown products were carried out
      by high performance liquid chromatography with diode-array detection (HPLC-DAD),
      liquid chromatography-tandem mass spectrometry (LC-MS/MS), and ultra high
      performance liquid chromatography with high mass accuracy quadrupole time-of
      flight mass spectrometry (UHPLC-Q-TOF-MS). 4-MEC became undetectable in blood
      within 14 days with a corresponding loss of 54% in plasma. A breakdown product
      was identified as dihydro-4-MEC which was also found in vivo in a case work
      sample. Storage of AMT led to a range of potential breakdown products which were
      also found in vivo. The remaining substances were found to be stable for at least
      21 days in blood and plasma. This is the first time stability data have been
      published for these emerging substances and showed that additional compounds
      found during forensic casework were potential metabolites rather than instability
      products. In particular, presumptive metabolites of 25C-NBOMe and AH-7921 are
      presented.

PMID- 24573921
TI  - Quantifying unrecognised replication present in reports of HIV diagnoses.
AB  - New diagnoses of HIV infection were reported confidentially to the Public Health
      Laboratory Service AIDS Centre under a national voluntary surveillance scheme.
      Two sets of data drawn from the national data sets were made available to us for
      analysis, the first in 1991 and the second in 1994, by which time the replication
      of reports had been reduced. The data used in the analyses consisted of the
      numbers of replications of the reported full date of birth in the individual
      records (one, two, three and so on), for each year of birth. This paper uses a
      nonparametric maximum likelihood estimation method for quantifying the amount of
      replication in the data. The estimated amount of replication was 3.37% (95%
      confidence interval (0.98%, 11.83%)) in the 1991 data set and 0.58% (95%
      confidence interval (0%, 2.64%)) in the 1994 data set.

PMID- 24573922
TI  - Current progress on internal medicine in China-2006 Part II.
AB  - A lot of progress has been made on internal medicine in the past year. Here a
      great deal of data were collected about internal medicine in China by searching
      for some most important medicine magazines published in China in 2006. Because
      there are so many articles on internal medicine, some representative reports were
      selected and further reviewed. In the part II, a summary of advances made in four
      branches includes nephrology, hematology, endocrinology and metabolism,
      rheumatology. 

PMID- 24573923
TI  - The change of serum leptin and its relationship with platelet membrane
      glycoprotein Ib in patients with coronary heart disease.
AB  - The aim of this paper was to investigate the change of serum leptin and its
      relationship with platelet membrane glycoprotein Ib (GP Ib) in patients with
      coronary heart disease (CHD). The enrolled included 50 patients with CHD (CHD
      group) and 30 patients without CHD (control group) who were diagnosed by coronary
      angiography. The positive percentage and the average fluorescence intensity of
      platelet membrane GP Ib were detected by full-blood flow cytometry. Serum leptin
      was detected by enzyme linked immunosorbent assay. The positive percentage and
      the average fluorescence intensity of platelet membrane GP Ib in the CHD group
      were significantly lower than those in the control group (P < 0.05). After
      correcting the differences of systolic blood pressure, body mass index (BMI), low
      density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol
      (HDL-C), fasting glucose, PPBS, fasting insulin and quantitative insulin
      sensitive index, serum leptin level in the CHD group was significantly higher
      than that in the control group (P < 0.05). Single factor correlative analysis
      revealed that serum leptin in CHD patients was negatively correlated with the
      average fluorescence intensity of platelet membrane GP Ib (P < 0.05).
      Multifactorial stepwise regression analysis showed that serum leptin in CHD
      patients was independently negatively correlated with the average fluorescence
      intensity of platelet membrane GP Ib (P < 0.05). Logistic analysis demonstrated
      that serum leptin was independently correlated with the risk of CHD (P < 0.05).
      Hyperleptinemia was verified in CHD patients. The increase of serum leptin could
      affect blood platelet activation. Hyperleptinemia may play an important role in
      the pathogenesis of CHD. 

PMID- 24573924
TI  - Effect of hyperlipidemia on endothelial VCAM-1 expression and the protective role
      of fenofibrate.
AB  - The effect of hyperlipidemia and inflammation on endothelial functions was
      studied. The enrolled included control (basic chow), hyperlipidemia and
      fenofibrate-treated groups (high fat diet). The hyperlipidemia model was set up
      by four-week atherogenic diet, followed by a 16-week treatment in the fenofibrate
      treated group (fenofibrate 40 mg/kg every day) and without treatment in the
      hyperlipidemia group, respectively. In the 20th week, serum lipid level and NO
      levels were measured, and the expression of vascular cell adhesion molecule-1
      (VCAM-1) and cell adhesiveness in aortic endothelia observed by computer-aided
      system. Compared with the control group, hyperlipidemia rats showed lower levels
      of NO and increases in leukocyte accumulation on the endothelial surface, also
      stronger and more extensive endothelial expression of VCAM-1. In fenofibrate
      treated group, the expression of VCAM-1 and leukocyte accumulation on the
      endothelial surface was decreased, while serum levels of NO were increased as
      compared with hyperlipidemia group. Hyperlipidemia can inhibit the NO activity
      and promote the damage of VACA-1 to aortic endothelia. Fenofibrate can
      effectively prevent the pathogenesis of atherosclerosis by restoring NO levels
      and down-regulating the VCAM-1 expression. 

PMID- 24573925
TI  - Impact of siRNA targeting pirh2 on proliferation and cell cycle control of the
      lung adenocarcinoma cell line A549.
AB  - The aim of this study was to investigate the role of pirh2 (p53-induced RING-H2)
      protein in the proliferation, apoptosis and cell cycle control of the lung cancer
      cell line A549. Pirh2 expression was detected by immunofluorescence, Western blot
      analysis and real-time polymerase chain reaction (PCR). Cell proliferation was
      assessed by cell counting kit-8 (CCK-8). Cell cycle control and apoptosis were
      analyzed by flow cytometry. The results showed that pirh2 was expressed in the
      cytoplasm of A549 cells. The inhibition of pirh2 expression by siRNA (psiRNA
      pirh2) resulted in reduced cell proliferation and increased apoptosis. In
      addition, the number of G0/G1 phase cells was increased but G2/M cells were not
      affected significantly. Taken together, the inhibition of pirh2 expression in the
      lung adenocarcinoma cell line A549 resulted in reduced tumor cell growth via the
      inhibition of cell proliferation, the activation of apoptosis and the
      interruption of cell cycle transition. 

PMID- 24573926
TI  - Change and significance of T-cell subsets and TNF-alpha in patients with advanced
      malignant obstructive jaundice treated by percutaneous transhepatic biliary
      external and internal drainage.
AB  - The aim of this article was to study the influence of immunity function of
      advanced malignant obstructive jaundice (MOJ) treated by percutaneous
      transhepatic biliary external and internal drainage. Ninety-six cases of MOJ were
      divided into two groups according to the different ways of biliary drainage.
      Fifty-two external drainage tubes were placed in 41 cases of percutaneous
      transhepatic biliary external drainage group and 66 metal stents were placed in
      55 cases of percutaneous transhepatic biliary internal drainage group. Liver
      function, serum TNF-alpha and cellular function were examined one day before
      operation and one week after operation and liver function was re-examined two
      weeks after operation, in order to observe the change and analyze the association
      among them and compare with the control group. All patients' conditions were
      improved after operation. In the percutaneous transhepatic biliary external and
      internal drainage groups, the total level of bilirubin decreased from (343.54+/
      105.56) MUmol/L and (321.19+/-110.50) MUmol/L to (290.56+/-103.46) MUmol/L and
      (283.72+/-104.95) MUmol/L after operation respectively, which were significantly
      lower than pre-operation (P<0.05), but there was no significant difference
      between the two groups (P>0.05). Serum alanine aminotransferase (ALT) of all
      patients one week after operation was significantly lower than that before
      operation. TNF-alpha in percutaneous transhepatic biliary external and internal
      groups decreased from (108.58+/-19.95) pg/mL, (109.98+/-16.24) pg/mL of pre
      operation to (104.32+/-19.59) pg/mL, (83.92+/-13.43) pg/mL of post-operation
      respectively, there was notable improvement (P<0.01) in internal drainage group
      after operation. Patients' serum CD4, CD3 and CD4/CD8 were notably increased, but
      CD8 was notably decreased (P<0.05). There was no difference in external drainage
      group (P>0.05). There was a significant difference between the two groups. Serum
      TNF-alpha and ALT had positive correlation. Percutaneous transhepatic biliary
      internal or external drainage was an effective and important method to treat MOJ.
      Patients' immune function was weak when they suffered MOJ, but body's cellular
      immune function can be notably improved after internal biliary drainage. 

PMID- 24573927
TI  - A novel method for reconstruction in laparoscopic pancreaticoduodenectomy: an
      experience of 13 cases.
AB  - Laparoscopic pancreaticoduodenectomy (LPD) is a challenging operation to general
      surgeon. Up to date, only about 135 cases have been reported, 16 cases in China,
      119 cases outside China. The reconstruction of alimentary system is a key
      procedure to ensure success of the whole surgery. It is worth investigating the
      methods of reconstruction in LPD. A retrospective study is made to investigate
      the methods of reconstruction in LPD. We analyze 13 cases of LPD performed in our
      center. Child's or modified Child's method was used to make the reconstruction in
      our practice. We tried three methods to make the anastomosis of
      pancreaticojejunostomy, including end-to-end dunking binding
      pancreaticojejunostomy in two cases, end-to-end dunking pancreaticojejunostomy
      using interrupted suture in two cases, and duct-to-jejunal end-to-side embedding
      pancreaticojejunostomy in nine cases. The clinical data was collected and
      analyzed. Three of four patients, who underwent end-to-end
      pancreaticojejunostomy, had a little pancreatic leakage, especially in the first
      case. None of other nine patients, who underwent duct-to-jejunal end-to-side
      embedding pancreaticojejunostomy, was detected to have pancreatic leakage, and
      the operating time of these nine cases was less than other four cases. Duct-to
      jejunal end-to-side embedding pancreaticojejunostomy is a safe and efficient
      method of reconstruction in LPD. 

PMID- 24573928
TI  - Biological features of intrahepatic CD4(+)CD25 (+) T cells in the naturally
      tolerance of rat liver transplantation.
AB  - The biological features of intrahepatic CD4(+) CD25(+) T regulatory cells in the
      naturally tolerance of rat liver transplantation were explored. Orthotopic liver
      transplantation was performed in two allogeneic rat strain combinations, one with
      fatal immunosuppression despite a complete major histocompatibility complex
      mismatch. The subjects were divided into three groups according to different
      donors and recipients [Tolerance group: LEW-to-DA; Rejection group: DA-to-LEW;
      Syngegnic group (control group): DA-to-DA]. The proportion of intrahepatic
      CD4(+)CD25(+) T cells from three groups was determined by flow cytometry (FCM) in
      different time. The intrahepatic CD4(+)CD25(+) T cells were isolated by magnetic
      activated cell sorting (MACS) method and identified by FCM. The Foxp3 mRNA was
      detected by reverse transcriptase polymerase chain reaction (RT-PCR). And their
      suppression on the proliferation of CD4(+)CD25(-) T effector cells was analyzed
      by cell proliferation assay in vitro. Beginning immediately after
      transplantation, the proportion of Treg cells increased over time in both
      allogeneic groups but was significantly greater in the Rejection group. The
      proportion of Treg cells declined after day 5, and such reduction was more
      dramatic in the Rejection group than in the Tolerance group. Animals in the
      Tolerance group showed a second increase in the proportion after day 14.
      Intrahepatic CD4(+) CD25(+) T cells isolated from spontaneous tolerance models
      inhibited the proliferation of mixed lymphocyte reaction. The purity of
      CD4(+)CD25(+) T cells sorted by MACS was 86%-93%. The CD4(+)CD25(+) T cells could
      specifically express the Foxp3 gene compared with CD4(+)CD25(-) T cells. In
      vitro, the spleen cells from LEW rats can irritate the proliferation of
      CD4(+)CD25(+) T cells more obviously than the syngegnic spleen cells.
      CD4(+)CD25(+) Tr cells could suppress the proliferation of CD4(+)CD25(-) T cells,
      but the inhibition was reversed by exogenous IL-2 (200 U/mL). The CD4(+)CD25(+) T
      regulatory cells specifically express the Foxp3 gene, which may play an important
      role in the induction of liver transplantation tolerance by suppressing the
      reaction of effective T cells. 

PMID- 24573929
TI  - Study of recombinant human IFN-alpha-2b bacilli calmette-guerin activated killer
      cells and against bladder cancer cell in vitro.
AB  - Presently, one of the most potent immunotherapies is the application of bacillus
      Calmette Guerin (BCG) to prevent recurrences of the superficial bladder cancer.
      Despite its successful use, nonresponders and certain side effects remain a major
      obstacle. Therefore, current studies aim at developing recombinant BCG (rBCG)
      strains secreting Th1-like cytokines to improve the effectiveness of the therapy.
      In this study, a new type of rBCG strain constructed by Tianjin institute of
      Urology was tested for its immunostimulatory capacity in vitro. Peripheral blood
      monocytes (PBMC) were stimulated by recombinant BCG and transformed into bacilli
      Calmette-Guerin activated killer (BAK) cells, and the effect of anticancer BAK
      cells was studied. Recombinant IFN-alpha-2b-BCG, wild-type BCG (wBCG), wild-type
      BCG and IFN-alpha-2b were coincubated with PBMCs respectively in vitro, and the
      proliferation of PBMC was detected with MTT in different time. BAK cells have the
      ability to kill bladder tumor cells, and the antitumor activity of effecter cells
      was determined by LDH release assay. The result of MTT showed that the
      proliferation of PBMC in the recombinant BCG group was more powerful than in the
      other two groups (P < 0.05). The result of LDH release assay showed that the
      antitumor activity of BAK cells stimulated by Recombinant BCG was the highest in
      all groups. We conclude that the recombinant BCG can activate more PBMCs to anti
      bladder cancer in vitro than wild-type BCG does. 

PMID- 24573930
TI  - Improved local control without elective nodal radiotherapy in patients with
      unresectable NSCLC treated by 3D-CRT.
AB  - To investigate the influence of prophylactic elective nodal irradiation on the
      therapeutic results of definitive radiotherapy for patients with stage IIIA or
      stage IIIB unresectable non-small-cell lung cancer, 55 patients with clinically
      inoperable advanced non-small-cell lung cancer were studied. After four cycles of
      induction chemotherapy, the patients were divided into two groups at random. In
      one group, the elective nodal irradiation was included in clinical tumor volume
      (CTV) of definitive radiotherapy (ENI group); and in the other group, elective
      nodal irradiation was not included in CTV (non-ENI group). For the patients in
      the ENI group, the mean prescription dose for gross tumor volumes was 58.4 Gy,
      while for the patients in the non-ENI group, it was 65.8 Gy (P < 0.05). The
      responsive rates were 45.8% and 74.0% (P < 0.05), and the rate of the elective
      nodal failure (ENF) was 4.2% and 11.1%, respectively. Kaplan-Meier analysis
      showed that the mean local-progression-free survival time was 11.0 and 15.0
      months, and one-year local-failure rates were 51.9% and 24.5% (P < 0.05). The
      median overall survival time was 13.0 and 15.0 months, respectively (P = 0.084).
      The one-year survival rates were 55.7% and 72.5%, and two-year survival rates
      were 0% and 19.9%. There was no significant difference in the occurrences of
      radiation-associated complications between the two groups. Our results showed
      that omitting elective nodal irradiation did not result in a high incidence of
      elective nodal failure. On the contrary, it decreased local failure by increasing
      prescription doses to the primary diseases and lymphadenopaphy, and thereby it
      may further prolong the patients' survival. 

PMID- 24573931
TI  - Relationship between expression of hepatocyte grow factor and apoptosis of
      trophoblasts in hypertensive disorder complicating pregnancy.
AB  - The aim of this study was to investigate the expression of hepatocyte growth
      factor (HGF) and Fas in placentas of uncomplicated pregnant women and those with
      hypertensive disorder complicating pregnancy (HDCP), and elucidate the possible
      relationship between HGF and apoptosis of trophoblasts. Reverse transcription
      polymerase chain reaction (RT-PCR) was undertaken to examine the concentration of
      HGF mRNA and Fas mRNA obtained from 34 cases of HDCP and 30 cases of
      uncomplicated pregnancy. The expression of HGF mRNA in mild preeclampsia, severe
      preeclampsia and eclampsia cases was significantly lower than that in the
      uncomplicated cases (0.43 +/- 0.12, 0.38 +/- 0.09, 0.19 +/- 0.17 versus 0.67 +/-
      0.19, P < 0.05), while the expression of Fas mRNA in mild preeclampsia, severe
      preeclampsia and eclampisa cases was significantly higher than that in the
      uncomplicated cases (1.58 +/- 0.26, 2.96 +/- 0.14, 5.98 +/- 1.17 versus 1.01 +/-
      0.36, P < 0.05). For HGF mRNA and Fas mRNA, there was no difference between
      gestational hypertension cases and control cases. Decreased HGF mRNA or increased
      Fas mRNA was found along with the progress of HDCP. Negative correlation was
      found between the expressions of HGF and Fas. These results indicate that HGF
      inhibits the apoptosis mediated by Fas, and the reduced expression of HGF in HDCP
      may be responsible for the apoptosis of trophoblasts. 

PMID- 24573932
TI  - Effects of galectin-3 inhibition on endometrial cell cycle and adhesion.
AB  - Galectin-3 (gal-3) and its ligands have been implicated in cell transformation
      and cancer metastasis. Gal-3 protein has been found in uterine epithelial cells
      adjacent to implanting blastocysts in different cell types. In order to
      investigate the role of gal-3 in the establishment of human endometrial
      receptivity, the expression of gal-3 in human endometrial cell line RL95-2 was
      silenced by RNA interference technology using gal-3 specific small RNA. The
      expression of gal-3 was detected by the reverse transcriptase-polymerase chain
      reaction and Western blot analysis. After the suppression of gal-3, cell cycle
      changes and the expression of integrin beta1 were detected by flow cytometry. The
      adhesive ability of RL95-2 cells was analyzed by the adhesion test. Gal-3 siRNA
      transfection efficiency reached 70%-90%. The expression of gal-3 mRNA and protein
      in RL95-2 cells was strongly inhibited by 70%-90% after RNA interference.
      Inhibition of gal-3 expression decreased S-phase but increased G1 phase cells.
      Integrin beta1 expression was down-regulated, and the adhesive ability of RL95-2
      cells to fibronectin (FN) was significantly reduced. Gal-3 may be involved in the
      establishment of endometrial receptivity by regulating the proliferation and
      adhesion of endometrial cells. The influence on adhesion may be related with the
      integrin modulation. 

PMID- 24573933
TI  - Relationship of adrenomedullin expression and microvessel density and prognosis
      in smooth muscle tumor of uterus.
AB  - The aim of this paper was to investigate the relationship between the expression
      of adrenomedullin (ADM) and microvessel density (MVD) and prognosis in smooth
      muscle tumor of uterus. The expression of ADM was detected using
      immunohistochemical staining in specimens from 15 normal controls, 28 cases of
      uterine leiomyoma (LE) and 19 cases of uterine leiomyosarcoma (LES). The MVD was
      assayed by immunostainting with CD34. There was a positive correlation between
      the ADM expression and MVD in LE and LES respectively (r s = 0.823, P < 0.01; r s
      = 0.793, P < 0.01). The expression of ADM in LE was statistically lower than that
      in LES (P < 0.05). There was a positive correlation between the ADM expression
      and mitotic figures in LES (P < 0.05): the more mitotic figures, the higher
      levels of the ADM expression and poor prognosis. The ADM is an important
      angiogenic factor in smooth muscle tumor of uterus. The ADM can be used as an
      accessory marker in estimating the malignant potency of LE and judging the
      prognosis of LES, and as a novel molecular target of anti-angiogenic and
      anticarcinogenic strategies. 

PMID- 24573934
TI  - Correlative investigation of copper/low-density polyethylene nanocomposite on the
      endometrial angiogenesis in rats.
AB  - The purpose of this study was to investigate the effects of copper/low-density
      polyethylene nanocomposite (nano-Cu/LDPE) on the endometrial angiogenesis in
      rats, and 100 sexual mature female SD rats were randomly divided into five
      groups: sham-operation groups (SO group, n = 20), bulk copper groups (Cu group, n
      = 20), LDPE groups (n = 20), nano-Cu/LDPE groups I (n = 20) and II (n = 20). The
      levels of angiopoietin-2 (Ang-2), its receptor (Tie-2) and CD34 of the rats'
      endometria in each group were examined by using the S-P method of the
      immunohistochemistry 30 and 180 days after insertion, respectively. Compared with
      those in the SO group, the expression of Ang-2 and Tie-2 in all the experimental
      groups was obviously increased 30 days after insertion, and these parameters in
      nano-Cu/LDPE groups, except for Ang-2 level in nano-Cu/LDPE group II, were
      significantly lower in comparison with those in Cu group (P < 0.05). On the 180th
      day after insertion, Ang-2 and Tie-2 levels were still higher in Cu group and
      LDPE group, but there was no difference of Ang-2 and Tie-2 levels between nano
      Cu/LDPE groups and the SO group (P > 0.05). Compared with those in the SO group,
      the significant increases in microvessel density (MVD) were observed on the 30th
      and the 180th day after the insertion of the bulk copper (P < 0.05). There was no
      significant difference in MVD counts before and after the insertion of nano
      Cu/LDPE (P > 0.05). The results show that Nano-Cu/LDPE have slighter influence on
      the endometrial angiogenesis than bulk copper. 

PMID- 24573935
TI  - Photodynamic therapy combined with intravitreal injection of triamcinolone
      acetonide for choroidal neovascularization.
AB  - The aim of this research was to evaluate the efficacy and safety of photodynamic
      therapy (PDT) combined with intravitreal injection of triamcinolone acetonide
      (TA) in the treatment of choroidal neovascularization (CNV) secondary to age
      related macular degeneration (AMD) and pathological myopia. PDT combined with
      intravitreal injection of TA was performed on 16 eyes of 16 patients with CNV
      diagnosed by visual acuity, fluorescein fundus angiography (FFA) and optical
      coherent tomography (OCT), including 14 eyes secondary to age-related macular
      degeneration and two eyes secondary to pathological myopia. TA was injected
      intravitreally 72 h post PDT on 12 eyes and from three months to one year (mean
      nine months) post PDT on four eyes respectively. All the patients were followed
      up for 3 to 18 months (mean 18.6 months). Best-corrected visual acuity,
      intraocular pressure, retinal thickness and FFA were observed. The visual acuity
      was improved in seven eyes (43.8%) of all the 16 eyes and stable in nine eyes
      (56.2%), respectively. FFA revealed complete or partial closure of CNV in all
      patients. OCT showed that the macular edema disappeared or was alleviated.
      Transient intraocular pressure elevation occurred in one patient (6.25%) of all
      the 16 eyes and intraocular pressure returned to the normal after a transient
      treatment with antiglaucoma medication. The mean number of PDTs during the first
      year was 1.1. PDT combined with intravitreal injection of TA for CNV is safe and
      effective. It can reduce the risk of visual loss and the treatment frequency. 

PMID- 24573936
TI  - Clinical study on the related markers of blood coagulation in the patients with
      ANFH after SARS.
AB  - The aim of this research was to investigate the blood coagulation function in the
      patients with avascular necrosis of the femoral head (ANFH) after severe acute
      respiratory syndrome (SARS). The expression of CD31, CD61, CD62p, CD63 and PAC-1
      on platelet membrane was measured respectively by flowcytometry, and the plasma
      prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin
      time (TT) and fibrinogen (Fbg) were measured by blood clotting instrument in 26
      patients with ANFH after SARS and in 17 healthy adults. The expression of CD31,
      CD61, CD 62p, CD63 and PAC-1 on platelet membrane in 26 patients was all lower
      than that in 17 healthy subjects (P < 0.01). The levels of PT, APTT, TT and Fbg
      in 26 patients were all normal. There is no significant difference (P > 0.05) in
      those markers between patients and 17 healthy adults. The blood may not be in
      hypercoagulable state in patients with ANFH after SARS. 

PMID- 24573937
TI  - Pathological study of 130 cases of nonalcoholic fatty liver disease based on NASH
      CRN system.
AB  - To summarize the pathological features of nonalcoholic liver disease (NAFLD) in
      China based on a histological scoring system for NAFLD designed by the Pathology
      Committee of NASH Clinical Research Network (NASH-CRN), the specimens of liver
      needle biopsies from 130 patients with NAFLD were histopathologically analyzed by
      haematoxylin eosin, reticular fiber and Masson trichrome stain.
      Immunohistochemistry staining was used to exclude non-NAFLD cases combined with
      clinical data. Hepatic steatosis, lobular inflammation, hepatocytic ballooning
      and fibrosis were presented widespread in NAFLD liver tissues. Furthermore,
      macrovesicular steatosis predominantly located in acinar zone 3 was the main
      histologic feature of NAFLD and lobular inflammation was usually presented
      mildly. Hepatocyte ballooning was observed in 94.6% of all 130 cases. Mild
      perisinusoidal fibrosis and periportal fibrosis were often observed in stage 1
      cases. According to the statistic analysis, hepatic steatosis was positively
      correlated with lobular inflammation, hepatocytic ballooning and fibrosis (r =
      0.587, 0.488, 0.374, respectively, all P value < 0.01). The number of
      microgranulomas, lipogranulomas and apoptotic bodies increased following severity
      of steatosis, lobular inflammation and fibrosis. Meanwhile, the number of
      megamitochondria and glycogen nuclei was paralleveled to the degree of
      hepatocytic ballooning (P value all < 0.01). We suggest that the role of portal
      inflammation should be emphasized besides hepatic steatosis, lobular
      inflammation, hepatocyte ballooning and fibrosis in diagnosis and evaluation of
      NAFLD. It needs to be further verified whether microgranulomas, lipogranulomas
      and apoptosis bodies could be used as histopathological markers of development of
      NAFLD. The number of megamitochondria is more frequently be found in NAFLD, while
      in alcoholic liver diseases was Mallory bodies. 

PMID- 24573938
TI  - Protective roles of heat stress on the neurons in hippocampal CA1 region of mice.
AB  - The effects of heat stress on the neurons in hippocampal CA1 region of brain
      ischemia/reperfusion were explored. The mice were pretreated with heat stress
      followed by ischemia/reperfusion by clipping bilateral cervical common arteries
      for 7 min. Mice were divided randomly into four groups as follows: (1) normal
      control group; (2) heat stress pretreated subsequent to ischemia/reperfusion
      group (HS/IR); (3) ischemia/reperfusion group (IR); and (4) heat stress group
      (HS). Animals in the last three groups were subdivided into three subgroups: 1 d,
      4 d, 14 d respectively. The Morris water maze was used to test the ability of
      learning and memorizing, Nissl staining was used to count the average number of
      survived neurons in hippocampal CA1 region, and immunohistochemistry combined
      with image analysis system to detect the changes of Microtubule associated
      protein 2 (MAP-2) expression. The results showed that mice in IR group exhibited
      increased escape latency when compared with that of normal, HS and HS/IR groups
      (P < 0.01), and the mice in IR group adopted an inefficient search strategy,
      major in circling and restricted searching manners. Nissl staining results showed
      a significant reduction in the number of pyramidal neurons in hippocampal CA1
      regions in HS/IR and IR groups, with a decrease in IR group (P < 0.01). Compared
      with normal group, the expression of MAP-2 in hippocampal CA1 region obviously
      decreased in IR group (P < 0.05). The present results indicate that heat stress
      pretreatment can improve the spatial learning and memorizing function through
      protection to hippocampal neurons. 

PMID- 24573939
TI  - The molecular epidemiological study of colistin-only-sensitive strains in multi
      drug resistant Acinetobacter baumannii.
AB  - This paper reported the epidemiology of the colistin-only-sensitive Acinetobacter
      baumannii (COS-AB) in a tertiary teaching hospital in China. We analyzed the
      clinical data of 136 COS-AB isolates from June 2004 to May 2005 and collected 66
      A. baumannii isolates in which 33 strains were COS-AB, and the rest were non-COS
      AB. Random amplified polymorphic DNA (RAPD) analysis (primer ERIC2 and 272)
      showed that all COS-AB were identical, while pulsed-field gel electrophotesis
      (PFGE) analysis showed two separate genotypes of these COS-AB which were
      distinctly different from that of non-COS-AB. The COS-AB from burn wards showed
      the identical PFGE pattern which was distinguished from the genotype of COS-AB in
      other departments, mainly surgical systems. The cross-infection was severe and
      strict methods of disinfection and sterilization should be implemented.
      Meanwhile, the epidemiology of COS-AB in environment and patients should be
      closely monitored. The PFGE analysis is a reliable method of A. baumannii typing.

PMID- 24573940
TI  - P50 auditory sensory gating in first onset schizophrenics and normal healthy
      adults.
AB  - The aim of this research was to investigate the variations of P50 auditory
      sensory gating (P50) in normal healthy adults and the first onset schizophrenics.
      By using the American Nicolet Bravo electromyography/evoked potential (EMG/EP)
      system, P50 was measured with conditioning-testing paradigm (paired-click stimuli
      S1 and S2 were used) in 58 first onset schizophrenics and 108 healthy adults, and
      the Positive and Negative Syndrome Scale (PANSS) was applied. The following three
      conclusions have been reached. (1) In normal control (NC) group, measured from
      central, anterior and posterior zone (Cz, Fz and Pz respectively), there were no
      statistical differences (P > 0.05) between S1 and S2 evoked P50 peak latencies
      (S1-P50 and S2-P50); the amplitudes of S2-P50 [(2.2 +/- 1.4), (2.3 +/- 1.5) and
      (2.1 +/- 1.4) MUV respectively] reduced significantly as compared with S1-P50
      [(5.6 +/- 3.3), (5.6 +/- 3.9) and (4.9 +/- 2.8) MUV respectively] (P < 0.01); the
      S2/S1 ration, S1-S2 difference, and 100 (1-S2/S1) had no statistical differences
      (P > 0.05). (2) Compared with NC, the schizophrenic group significantly showed
      lower S1-P50 amplitudes (P < 0.01, except at Pz in which Z = 2.030, P = 0.042),
      higher S2-P50 amplitudes, higher S2/S1 ratio, lower S1-S2 difference, and more
      decreased 100 (1-S2/S1) (P < 0.01) at Cz, Fz and Pz. (3) No significant
      correlations were found among S2/S1 ratio, S1-S2, 100 (1-S2/S1) of sensory gating
      and PANSS (P > 0.05) in schizophrenic group. The first onset schizophrenics had
      sensory gating deficits, which could be quantified by P50. 

PMID- 24573941
TI  - Effect of oxytocin on gastric ischemia-reperfusion injury in rats.
AB  - The effect of peripherally administered oxytocin (OT) on gastric ischemia
      reperfusion injury (GI-RI) and its possible mechanism were investigated. The
      Sprague-Dawley (SD) rats were randomly divided into different treatment groups (n
      = 6). The animal GI-RI model was established by clamping the celiac artery for 30
      min to induce ischemia and then released to allow reperfusion for 1 h, and the
      degree of GI-RI was assessed by scoring the gastric mucosal damage index (GMDI),
      the gastric fluid output, gastric fluid output, gastric acidity were measured and
      the surgical preparations of vagotomy and sympathectomy were used to investigate
      the possible mechanism of OT on GI-RI. The results were as follows. Compared with
      the control group (NS plus GI-R only, GMDI 121.33 +/- 10.40, n = 6), the
      intraperitoneal (ip) administration of oxytocin (20, 100 MUg/0.5 mL) obviously
      attenuated GI-RI (P < 0.05), GMDI were 82.33 +/- 14.26, 53.5 +/- 5.58
      respectively (n = 6); the gastric fluid output and the gastric acidity (evaluated
      by pH) of the control group were (430.17 +/- 87.36) MUL, 1.55 +/- 0.25 (n = 6),
      and those of the OT group were (102.45 +/- 48.00) MUL, 2.65 +/- 0.40 (n = 6)
      respectively; differences had statistical significance (P < 0.01). The effect of
      oxytocin was reversed by atosiban, a selective oxytocin receptor antagonist. The
      GMDI of the group given atosiban 10 min before OT was 138.17 +/- 24.06 (n = 6),
      which had no significant difference with the control group. Oxytocin further
      attenuated GI-RI after vagotomy and sympathectomy (GMDI 6.83 +/- 8.89, 29.67 +/-
      5.54, n = 6), compared with the GI-R group and the oxytocin group (P < 0.01).
      These results indicated that the oxytocin could significantly protect gastric
      mucosal against injury induced by ischemia-reperfusion, and the oxytocin receptor
      was involved. This effect of oxytocin may be mediated through the vagus and
      sympathetic nerve, and then lead to the reduction of gastric juice output and the
      depression of gastric acidity. 

PMID- 24573944
TI  - Confined iron fluoride@CMK-3 nanocomposite as an ultrahigh rate capability
      cathode for Li-ion batteries.
AB  - A facile and advanced architecture design of FeF3.0.33H2O impregnated CMK-3
      nanocomposite (FeF3.0.33H2O@CMK-3) is presented. In the FeF3.0.33H2O@CMK-3
      nanocomposite, mesoporous carbon CMK-3 can provide enough passageways for
      electron and Li(+) transport to the confined nanosized FeF3.0.33H2O. The intimate
      conductive contact between the FeF3.0.33H2O nanoparticles and the carbon
      framework not only provides an expressway of electron transfer for Li(+)
      insertion/extraction but also suppresses the growth and agglomeration of
      FeF3.0.33H2O during the crystallization process. As expected, the nanostructured
      materials exhibit impressive rate capability and excellent cyclicity. Remarkably,
      even under an ultrahigh charge/discharge rate of 50 C (the charge or discharge
      process takes a mere 72 s), the confined FeF3.0.33H2O@CMK-3 still shows a high
      specific capacity of 78 mAh g(-1). By combining confined nanosized active
      material, high electron conductivity, and open framework, the FeF3.0.33H2O@CMK-3
      nanocomposite demonstrates excellent high-rate capability and good cycling
      properties.

PMID- 24573946
TI  - Notice of redundant publication.

PMID- 24573945
TI  - An improved technique for the rapid chemical characterisation of bacterial
      terpene cyclases.
AB  - A derivative of the pET28c(+) expression vector was constructed. It contains a
      yeast replication system (2MU origin of replication) and a yeast selectable
      marker (URA3), and can be used for gene cloning in yeast by efficient homologous
      recombination, and for heterologous expression in E. coli. The vector was used
      for the expression and chemical characterisation of three bacterial terpene
      cyclases. 

PMID- 24573948
TI  - [Stimulating mental health services research: what are the implications of the
      new DGPPN S3-guideline for psycho-social therapies?].

PMID- 24573942
TI  - Episodic memory impairment in Addison's disease: results from a telephonic
      cognitive assessment.
AB  - Patients with Addison's disease frequently self-report memory and attention
      difficulties, even when on standard replacement therapy. However, few published
      studies examine, using objective measures and assessing across multiple domains,
      the cognitive functioning of Addison's disease patients relative to healthy
      controls. The primary aim of this study was to investigate whether the previously
      reported subjective cognitive deficits in Addison's disease are confirmed by
      objective measures. Conducting comprehensive neuropsychological assessments of
      patients with relatively rare clinical disorders, such as Addison's disease, is
      challenging because access to those patients is often limited, and because their
      medical condition might prevent extended testing sessions. Brief telephonic
      cognitive assessments are a useful tool in such circumstances. Hence, we
      administered the Brief Test of Adult Cognition by Telephone to 27 Addison's
      disease patients and 27 matched healthy controls. The instrument provides
      objective assessment of episodic memory, working memory, executive functioning,
      reasoning, and speed of processing. Statistical analyses confirmed that, as
      expected, patients performed significantly more poorly than controls on the
      episodic memory subtest. There were, however, no significant between-group
      differences on the attention, executive functioning, reasoning, and speed of
      processing subtests. Furthermore, patients with a longer duration of illness
      performed more poorly across all domains of cognition. We conclude that, for
      Addison's disease patients, previously reported subjective cognitive deficits are
      matched by objective impairment, but only in the domain of episodic memory.
      Future research might investigate (a) whether these memory deficits are material
      specific (i.e., whether non-verbal memory is also affected), and (b) the
      neurobiological mechanisms underlying these deficits. 

PMID- 24573949
TI  - [Guardianship law: well meant, but deficiently realized - pro].

PMID- 24573950
TI  - [Guardianship law: well meant, but deficiently realized - contra].

PMID- 24573953
TI  - A flexible wide-field FLIM endoscope utilising blue excitation light for label
      free contrast of tissue.
AB  - Fluorescence lifetime imaging (FLIM) has previously been shown to provide
      contrast between normal and diseased tissue. Here we present progress towards
      clinical and preclinical FLIM endoscopy of tissue autofluorescence, demonstrating
      a flexible wide-field endoscope that utilised a low average power blue picosecond
      laser diode excitation source and was able to acquire ~mm-scale spatial maps of
      autofluorescence lifetimes from fresh ex vivo diseased human larynx biopsies in
      ~8 seconds using an average excitation power of ~0.5 mW at the specimen. To
      illustrate its potential for FLIM at higher acquisition rates, a higher power
      mode-locked frequency doubled Ti:Sapphire laser was used to demonstrate FLIM of
      ex vivo mouse bowel at up to 2.5 Hz using 10 mW of average excitation power at
      the specimen.

PMID- 24573955
TI  - Suppression of Hedgehog signalling promotes pro-tumourigenic integrin expression
      and function.
AB  - Aberrant Hedgehog (Hh) signalling has been reported in a number of malignancies,
      particularly basal cell carcinoma (BCC) of the skin. Clinical trials of Hh
      inhibitors are underway in many cancers, and these have produced significant
      clinical benefit in BCC patients, although regrowth of new, or clinically
      aggressive, variants, as well as development of secondary malignancies, has been
      reported. alphavbeta6 integrin is expressed in many cancers, where it has been
      shown to correlate with an aggressive tumour phenotype and poor prognosis. We
      have previously reported alphavbeta6 up-regulation in aggressive, morphoeic BCC
      variants, where it modulates the stromal response and induces invasion. To
      examine a possible link between Hh and alphavbeta6 function, we generated BCC
      models, overexpressing Gli1 in immortalized keratinocytes (NTert1, HaCaT).
      Unexpectedly, we found that suppressing Gli1 significantly increased alphavbeta6
      expression. This promoted tumour cell motility and also stromal myofibroblast
      differentiation through integrin-dependent TGF-beta1 activation. Gli1 inhibited
      alphavbeta6 expression by suppressing TGF-beta1-induced Smad2/3 activation,
      blocking a positive feedback loop maintaining high alphavbeta6 levels. A similar
      mechanism was observed in AsPC1 pancreatic cancer cells expressing endogenous
      Gli1, suggesting a common mechanism across tumour types. In vitro findings were
      supported using human clinical samples, where we showed an inverse correlation
      between alphavbeta6 and Gli1 expression in different BCC subtypes and pancreatic
      cancers. In summary, we show that expression of Gli1 and alphavbeta6 inversely
      correlates in tumours in vivo, and Hh targeting up-regulates TGF-beta1/Smad2/3
      dependent alphavbeta6 expression, promoting pro-tumourigenic cell functions in
      vitro. These results have potential clinical significance, given the reported
      recurrence of BCC variants and secondary malignancies in patients treated by Hh
      targeting.

PMID- 24573957
TI  - Changes in the prevalence of new psychoactive substances before and after the
      introduction of the generic scheduling of synthetic cannabinoids in Japan.
AB  - To counter the spread of the many analogues of psychoactive substances, the
      Pharmaceutical Affairs Law in Japan was amended in 2006 to establish a new
      category - Designated Substances - in order to more promptly control these drugs.
      As of March 2013, 106 substances (including one plant, Salvia divinorum) were
      listed in the category of Designated Substances, and 13 of them had had their
      category changed from Designated Substances into the much stricter category,
      Narcotics. However, new analogues of controlled substances, especially synthetic
      cannabinoids, appeared one-by-one since the new category was introduced. To avoid
      a cat-and-mouse game between regulators and illicit drug manufacturers, a
      comprehensive system (generic scheduling) for designating naphthoylindole-type
      synthetic cannabinoids, with particular substituents, was introduced into the
      Designated Substances in 2013. Since late 2012, the naphthoylindole-type
      compounds have been gradually replaced by other types of synthetic cannabinoids,
      such as cyclopropylmethanones, cannabimimetic carboxamide derivatives,
      adamanthoyl indoles, and cannabimimetic quinolinyl carboxylates. After the
      enforcement of the generic scheduling for designating naphthoylindoles in March
      2013, these naphthoylindoles have been completely replaced by other types and
      have rarely been detected in the products. New types of psychoactive substances,
      including opioid receptor agonists (e.g. AH-7921, MT-45), hallucinogenic
      phenethylamines (e.g. NBOMe-type compounds), and thiophene derivatives (e.g.
      methiopropamine, alpha-PVT) have also appeared. The almost infinite possibilities
      of altered structures of chemicals make it difficult to carry out effective and
      exhaustive scheduling. To prevent the widespread distribution and abuse of these
      new psychoactive substances, continuous and dedicated monitoring for the
      emergence of these substances is necessary.

PMID- 24573956
TI  - Apoptosis-associated genes related to photodynamic therapy in breast carcinomas.
AB  - The aim of this study was to find the apoptosis molecular markers involved in the
      cell death that might be related to photodynamic therapy (PDT) mechanisms in
      breast cancer. The mammary tumors were induced in 25 Sprague-Dawley female rats
      by a single, oral gavage of 7,12-dimethylbenz(a)anthracene (DMBA; 70 mg/kg body
      weight). Animals were divided into four groups: G1 (normal, without DMBA), G2
      (control, without PDT treatment), G3 (euthanized 48 h after PDT), and G4
      (euthanized 24 h after PDT). For PDT experiments, the photosensitizer used was
      Photodithazine, and 100 J/cm of light at a fluence rate of 100 mW/cm was
      delivered to treat lesions. A sample of each animal was investigated by
      quantitative real-time PCR using Rat Apoptosis RT2 ProfilerTM PCR Array platform.
      The results showed 20 genes with differential expression between PDT and control
      groups. A significant upregulation was observed for pro-apoptotic genes CASP4,
      CASP12, CIDEA, GADD45A, and FAS and downregulation of anti-apoptotic genes
      MAPK8IP1, TNFRSF11B, and NAIP2 in PDT-treated tumors. These results indicate that
      these genes are more directly involved in cell apoptosis induced by PDT.

PMID- 24573958
TI  - siRNA technology in kidney transplantation: current status and future potential.
AB  - Kidney transplantation is one of the most common transplantation operations in
      the world, accounting for up to 50 % of all transplantation surgeries. To curtail
      the damage to transplanted organs that is caused by ischemia-reperfusion injury
      and the recipient's immune system, small interfering RNA (siRNA) technology is
      being explored. Importantly, the kidney as a whole is a preferential site for non
      specific systemic delivery of siRNA. To date, most attempts at siRNA-based
      therapy for transplantation-related conditions have remained at the in vitro
      stage, with only a few of them being advanced into animal models. Hydrodynamic
      intravenous injection of naked or carrier-bound siRNAs is currently the most
      common route for delivery of therapeutic constructs. To our knowledge, no
      systematic screens for siRNA targets most relevant for kidney transplantation
      have been attempted so far. A majority of researchers have arrived at one or
      another target of interest by analyzing current literature that dissects
      pathological processes taking place in transplanted organs. A majority of the
      genes that make up the list of 53 siRNA targets that have been tested in
      transplantation-related models so far belong to either apoptosis- or immune
      rejection-centered networks. There is an opportunity for therapeutic siRNA
      combinations that may be delivered within the same delivery vector or injected at
      the same time and, by targeting more than one pathway, or by hitting the same
      pathways within two different key points, will augment the effects of each other.

PMID- 24573959
TI  - Analysis of 16 STRs of NOS gene regions and around in six Sardinian populations
      (Italy).
AB  - OBJECTIVES: The aims of this work are to provide first data on novel STRs at the
      NOS gene regions in human populations and to test for possible correlations with
      mortality rate by malaria in different areas of Sardinia (Italy). METHODS: In the
      present study, 16 STRs (13 analyzed for the first time in human populations)
      localized on three genes NOS were typed in 213 healthy individuals, unrelated for
      at least three generations, from six historical-geographical Sardinian areas.
      STRs alleles were determined through sequencing. Statistical analyses were
      performed by Genepop (v.4.0), Arlequin (v.3.5.1.2), R (v.2.15.1), Statistica
      (v.5.1), and PHASE (v.2.1) software packages. RESULTS: The number of alleles
      found for each locus ranged from 2 to 12 and their distribution is most often
      unimodal. All populations met Hardy Weinberg equilibrium after Bonferroni
      correction, with few exceptions. Analysis of genetic distances did not show
      strong genetic structuring of the investigated populations. Instead, the
      population genetic variability shows a positive and highly significant (P-value <
      0.01) correlation between mortality determined by malaria infection and alleles
      (TGGA)7 of NOS2, (AAAAG)2 and (ATTT)10 of adNOS1, and (AAACA)11 of adNOS3 genes.
      CONCLUSIONS: The peculiar allele distribution found for several NOS alleles could
      be due to malaria infection that may have contributed to their frequencies, but
      we cannot exclude that the peculiar allele distribution of NOS might also be due
      to genetic drift, emphasized by isolation and founder effect.

PMID- 24573961
TI  - Pseudopapilledema and association with idiopathic intracranial hypertension.
AB  - PURPOSE: Diagnosing idiopathic intracranial hypertension (IIH), or pseudotumor
      cerebri, can be challenging in children. Diagnosis is based on lumbar puncture,
      opening pressures, and appearance of the optic disk. Misdiagnosis of papilledema,
      a typical finding, may lead to unnecessary treatments and procedures. We report
      52 children over a 6-year period to better identify the true incidence of
      pseudopapilledema and other factors that may confound the diagnosis of IIH.
      METHODS: A retrospective chart review approved by the Institutional Review Board
      was performed. Fifty-two children under the age of 21 referred to us based on
      suspected IIH or papilledema from 2007 to 2013 are included in this study.
      Patients were assessed by a pediatric ophthalmologist and a neurosurgeon.
      RESULTS: Fifty-two children were initially diagnosed with IIH and/or papilledema;
      26 diagnoses were revised to pseudopapilledema after pediatric ophthalmological
      review. Out of those 26 patients with pseudopapilledema, 14 had undergone lumbar
      punctures, 19 had MRIs, 9 had CTs, and 12 were taking medications-these
      medications were discontinued upon revision of the diagnoses. The difference in
      the CSF opening pressure between children diagnosed with true IIH (32.7 cm H2O)
      and children diagnosed with pseudopapilledema (24.7 cm H2O) was statistically
      significant. CONCLUSIONS: IIH diagnosis is heavily reliant on the appearance of
      the optic disk. Pediatric ophthalmological assessment is essential to carefully
      examine the optic disk and prevent further unnecessary investigation and
      treatments. Close communication between pediatricians, ophthalmologists, and
      neurosurgeons can avoid invasive procedures for children who do have
      pseudopapilledema, and not IIH or associated papilledema.

PMID- 24573967
TI  - Long- and short-term indoor radon survey in the Ardea municipality, south Rome.
AB  - The indoor radon concentration was measured in 16 schools and 6 public
      departments in the Ardea municipality, using both active and passive detectors.
      The annual concentration of radon has been determined as the mean of two
      consecutive 6-month periods of sampling from January 2012 to January 2013. The
      indoor radon level measured in the monitored buildings ranged from 17 to 918
      Bq.m(-3), with a mean value of 154 Bq.m(-3). In addition, the correlation between
      short-term and long-term measurements was studied. Experimental data demonstrate
      that the deviation of short-term measurements with respect to polyallyl diglycol
      carbonate data does not exceed +/-40 % in a very extended range of radon
      concentrations. 

PMID- 24573962
TI  - Roux-en-Y esophagojejunostomy reduces serum and aortic inflammatory biomarkers in
      type 2 diabetic rats.
AB  - BACKGROUND: Recent studies have shown the reduction in serum inflammatory
      biomarkers by bariatric surgery. However, few studies have reported its effects
      on local vascular inflammation. We have investigated the effects of Roux-en-Y
      esophagojejunostomy on both serum and aortic tissue inflammation biomarkers in
      type 2 diabetic rats. METHODS: Sprague-Dawley rats were divided into five groups:
      diabetic RYEJ, diabetic RYEJ sham, diabetic food restriction, diabetic rats, and
      non-diabetic control (n = 6/group). At 4 weeks after surgery, serum leptin,
      interleukin-6, C-reactive protein, interleukin-1beta (IL-1beta), tumor necrosis
      factor-alpha (TNF-alpha), chemerin, and adiponectin were measured. Aortic
      expression of c-Jun NH2-terminal kinase and p38 mitogen-activated protein kinases
      was examined with immunohistochemistry; aortic expression of IL-1beta, TNF-alpha,
      intercellular adhesion molecule-1, and vascular adhesion molecule-1 was assessed
      with western blotting. Hyperinsulinemic-euglycemic clamps with tracer infusion
      were completed to assess insulin sensitivity. RESULTS: Roux-en-Y
      esophagojejunostomy significantly decreased serum inflammatory parameters and
      increased the concentration of the anti-inflammatory mediator adiponectin. The
      aortic inflammatory protein expression was markedly decreased in the diabetic
      RYEJ group as compared with that of the diabetic group (P < 0.05). Additionally,
      Roux-en-Y esophagojejunostomy improved insulin sensitivity and dyslipidemia and
      decreased body weight and total body fat. CONCLUSIONS: Roux-en-Y
      esophagojejunostomy reduces the systemic and local vascular inflammation. The
      improvements in systemic and vascular inflammation are not wholly dependent on
      the magnitude of weight loss. Moreover, Roux-en-Y esophagojejunostomy alleviates
      insulin resistance and improves the features of metabolic syndrome, leading to a
      reduction in multiple cardiovascular risks.

PMID- 24573968
TI  - Cosmic-ray neutron simulations and measurements in Taiwan.
AB  - This study used simulations of galactic cosmic ray in the atmosphere to
      investigate the neutron background environment in Taiwan, emphasising its
      altitude dependence and spectrum variation near interfaces. The calculated
      results were analysed and compared with two measurements. The first measurement
      was a mobile neutron survey from sea level up to 3275 m in altitude conducted
      using a car-mounted high-sensitivity neutron detector. The second was a previous
      measured result focusing on the changes in neutron spectra near air/ground and
      air/water interfaces. The attenuation length of cosmic-ray neutrons in the lower
      atmosphere was estimated to be 163 g cm(-2) in Taiwan. Cosmic-ray neutron spectra
      vary with altitude and especially near interfaces. The determined spectra near
      the air/ground and air/water interfaces agree well with measurements for neutrons
      below 10 MeV. However, the high-energy portion of spectra was observed to be much
      higher than our previous estimation. Because high-energy neutrons contribute
      substantially to a dose evaluation, revising the annual sea-level effective dose
      from cosmic-ray neutrons at ground level in Taiwan to 35 MUSv, which corresponds
      to a neutron flux of 5.30 * 10(-3) n cm(-2) s(-1), was suggested. 

PMID- 24573969
TI  - Da Vinci robot-assisted system for thymectomy: experience of 55 patients in
      China.
AB  - BACKGROUND: Da Vinci robot-assisted thymectomy has been used in the past several
      years in China, however, practical experience in performing this approach in
      China remains limited. Thus, the study aimed to evaluate the experience of da
      Vinci robot-assisted thymectomy in China. METHODS: From June 2010 to December
      2012, 55 patients with diseases of the thymus underwent thymectomy using the da
      Vinci surgical HD robotic system. The clinical data of the da Vinci robot
      assisted thymectomies were compared with the data of video-assisted thoracoscopic
      thymectomies in the same period. RESULTS: All da Vinci robot operations were
      successful. This is a retrospective analysis which demonstrated that compared
      with video-assisted thoracoscopic thymectomy in the same period, the clinical
      outcomes of da Vinci robot-assisted thymectomy were not significantly different.
      CONCLUSION: The da Vinci robot-assisted thymectomy is a safe, minimally invasive,
      and convenient operation, and shows promise for general thoracic surgery in
      China.

PMID- 24573970
TI  - Cross-linked, self-fluorescent gold nanoparticle/polypeptide nanocapsules
      comprising dityrosine for protein encapsulation and label-free imaging.

PMID- 24573960
TI  - Central nervous system circuits modified in heart failure: pathophysiology and
      therapeutic implications.
AB  - The pathophysiology of heart failure (HF) is characterized by an abnormal
      activation of neurohumoral systems, including the sympathetic nervous and the
      renin-angiotensin-aldosterone systems, which have long-term deleterious effects
      on the disease progression. Perpetuation of this neurohumoral activation is
      partially dependent of central nervous system (CNS) pathways, mainly involving
      the paraventricular nucleus of the hypothalamus and some regions of the
      brainstem. Modifications in these integrative CNS circuits result in the
      attenuation of sympathoinhibitory and exacerbation of sympathoexcitatory
      pathways. In addition to the regulation of sympathetic outflow, these central
      pathways coordinate a complex network of agents with an established
      pathophysiological relevance in HF such as angiotensin, aldosterone, and
      proinflammatory cytokines. Central pathways could be potential targets in HF
      therapy since the current mainstay of HF pharmacotherapy aims primarily at
      antagonizing the peripheral mechanisms. Thus, in the present review, we describe
      the role of CNS pathways in HF pathophysiology and as potential novel therapeutic
      targets. 

PMID- 24573971
TI  - Cisatracurium pretreatment with tourniquet reduces propofol injection pain: a
      double-blind randomized controlled trial.
AB  - OBJECTIVES: To investigate the efficacy of pretreatment with cisatracurium for
      prevention of pain associated with propofol injection, and compare its efficacy
      with that of lidocaine. METHODS: Patients undergoing general anaesthesia were
      randomized to receive normal saline (control group), lidocaine (0.5 mg/kg), 0.03
      mg/kg cisatracurium or 0.15 mg/kg cisatracurium. All drugs were administered into
      the largest dorsal vein of the hand with venous occlusion for 30 s, followed by
      propofol (0.5 mg/kg). Pain was evaluated using a four-point scale. RESULTS: The
      incidence and severity of pain was significantly lower in the lidocaine and 0.15
      mg/kg cisatracurium groups than the control and 0.03 mg/kg cisatracurium groups
      (n = 50/group). There was no significant difference between the lidocaine and
      0.15 mg/kg cisatracurium groups in the incidence and severity of pain.
      CONCLUSIONS: 0.15 mg/kg cisatracurium effectively decreases the incidence and
      severity of pain induced by propofol injection without any significant
      complications.

PMID- 24573972
TI  - The value of inflammatory parameters in the prognosis of malignant mesothelioma.
AB  - OBJECTIVE: This study investigated the relationship between potential prognostic
      parameters that may be associated with increased inflammation and survival in
      patients with malignant mesothelioma (MM). METHODS: This retrospective study
      assessed potential prognostic parameters measured at the time of MM diagnosis.
      Data on asbestos exposure, histopathological subtype of MM and laboratory
      parameters were collected. RESULTS: In 155 patients with MM (90 male), mean
      survival time was 13.9 months. In univariate analysis, age >= 60 years and
      neutrophil-to-lymphocyte ratio (NLR) >= 3 were associated with significantly
      shortened median survival times. In multivariate analysis, nonepithelial subtype,
      red cell distribution width (RDW) >= 20% and NLR >= 3 were associated with
      significantly shortened median survival times. Mortality rate was increased 2.77
      , 1.67- and 1.52-fold in patients with RDW >= 20%, NLR >= 3 and nonepithelial
      subtype, respectively. Nonepithelial subtype, white blood cell count >= 11 200 ul
      and platelet-to-lymphocyte ratio >= 300 at baseline were associated with a
      heightened NLR value. CONCLUSIONS: The NLR and RDW were significant predictive
      factors for MM prognosis.

PMID- 24573973
TI  - New endoscopic classification system for biliary stricture after liver
      transplantation.
AB  - AIM: A new classification system for biliary stricture (BS) after liver
      transplantation (LT) is proposed, aiming to standardize endoscopic treatment for
      this condition. METHODS: Data were retrospectively collected from patients who
      had undergone endoscopic retrograde cholangiography after LT, and who provided
      endoscopy images clear enough to reveal the biliary system. Images were
      classified separately by two endoscopists, who discussed and resolved any
      disputed findings. From these images, a new classification system is proposed
      (Ling classification): type A, normal biliary structure; type B, anastomotic
      stricture and normal intrahepatic biliary structure; type C, narrow and stiff
      intrahepatic biliary structure or beaded intrahepatic biliary structure or
      intrahepatic biliary cast without anastomotic stricture; type D, narrow and stiff
      intrahepatic biliary structure or beaded intrahepatic biliary structure or
      intrahepatic biliary cast with anastomotic stricture. RESULTS: Analysis involved
      93 patients: 76 men and 17 women, median age 54 years (range, 12-69 years). Type
      B was the most commonly observed BS after LT, accounting for 44 cases (47.3%).
      Type A, the least commonly observed type, accounted for nine (9.7%), type C for
      22 (23.7%) and type D for 18 (19.3%) cases. CONCLUSION: A new endoscopic
      classification system for BS after LT is proposed, to help determine the most
      appropriate treatment for patients with each type of stricture.

PMID- 24573974
TI  - Efficacy of acellular dermal matrix and autogenous connective tissue grafts in
      the treatment of gingival recession defects among Asians.
AB  - INTRODUCTION: The aim of the present study was to assess the efficacy of
      acellular dermal matrix (ADM) and subepithelial connective tissue grafts (sCTG)
      in the treatment of Miller class I and II gingival recession (GR) defects.
      METHODS: Six patients with eight GR sites were randomly assigned to the test
      group (GR defects treated with ADM) and control group (GR defects treated with
      sCTG). Recession height (RH) and width, probing depth, keratinized gingiva,
      clinical attachment level, and full mouth plaque and bleeding scores were
      measured at baseline, 3 and 6 months. RESULTS: The differences in mean changes
      were insignificant between the two groups in all parameters. In both groups,
      improvements from baseline to 3 and 6 months were significant for mean RH
      reduction and clinical attachment gain. A significant increase in the mean
      keratinized gingiva width was observed in both groups at 3 and 6 months.
      CONCLUSION: ADM and sCTG yield similar outcomes when used in the treatment of GR
      defects.

PMID- 24573975
TI  - Changes in dopamine release and dopamine D2/3 receptor levels with the
      development of mild obesity.

PMID- 24573976
TI  - Levels of antioxidants in the spinal fluid after induction of anesthesia with
      ropivacaine.
AB  - Anesthesia is a loss of sensation or consciousness and mechanisms by which drugs
      can produce this state are not clear. Recent studies gave insight show anesthetic
      agents may lead to loss of consciousness at the molecular level. The objective of
      this study was to determine whether ropivacaine can influence antioxidant defense
      system.To analyze the response of the antioxidant defense system to ropivacaine
      samples were taken from the vein before anesthesia (0 min) and 5 min, 15 min, and
      60 min after anesthesia. Subsequently, the levels of lipid peroxidation as
      melaninedialdehyde (MDA) and glutathione (GSH), as well as superoxide dismutase
      (SOD) and catalase (CAT) activities were measured.We observed moderate increase
      in lipid peroxidation and glutathione levels. More-over, the activity of
      superoxide dismutase was slightly enhanced. These alterations occurred 5 min
      after spinal injection of ropivacaine and this phenomenon was maintained
      throughout anesthesia. We measured decreased catalase activity starting from 5
      min after anesthesia and activity of this antioxidant enzyme was not recovered
      even after 60 min of anesthesia.We found that spinal injection of ropivacaine
      results in increased levels of free radicals in spinal fluid, which may stimulate
      antioxidant defense system of spinal fluid during anesthesia. 

PMID- 24573977
TI  - Assessment of antibacterial activity of smaller chain tripeptides and
      tetrapeptides.
AB  - Our objective is to investigate the smaller chain tripeptides and tetrapeptides
      with the efforts mainly directed towards the identification of compounds
      presenting a high bactericidal activity. In this connection, 5 peptides, Met-Arg
      Tyr (MRY), Met-Val-Tyr (MVY), Met-Ile-Cys-Tyr (MICY), Phe-Trp-Lys-Tyr (FWKY) and
      Met-Trp-Lys-Tyr (MWKY) were synthesized by solid phase peptide synthesis. The
      column eluted pure synthesized compounds were tested for in-vitro antibacterial
      disc diffusion assay using 2 g positive S. aureus, B.subtilis and 1 g negative
      E.coli bacterial strains at different concentrations predicted by pH and
      inhibitory concentration findings. 2 of the tetrapeptides, Phe-Trp-Lys-Tyr (FWKY)
      and Met-Trp-Lys-Tyr (MWKY) were found to be highly efficient against all the gram
      positive and microbial strains tested. Maximum activity was observed at a
      concentration of 300 ug/ml (499.17 uM) for the tetrapeptide Phe-Trp-Lys-Tyr
      (FWKY) against B. subtilis and at a concentration of 450 ug/ml (748.75 uM)
      against E. coli with the corresponding zonal inhibition diameter readings (17 mm;
      16 mm). The tetrapeptide Met-Trp-Lys-Tyr (MWKY) was found to have high potency
      against S. aureus at a concentration of 450 ug/ml (769.23 uM) with the
      corresponding zonal inhibition diameter as 13 mm. The experimental results are
      analysed statistically by t-test at 5% and 1% level of significance. Our
      tetrapeptides have shown antibacterial action against both gram positive and gram
      negative strains and are considered safer as par with commercial antibiotics
      available today. Further clinical studies will make sure to position our potent
      small chain tetrapeptides in the arsenal of new broad spectrum anti-gram positive
      and anti-gram negative agent. 

PMID- 24573978
TI  - Synthesis and biological evaluation of a new angiotensin II receptor antagonist.
AB  - The design, synthesis, in vitro and in vivo evaluation of (2 R,6 S)-4-({1-[2-(1 H
      tetrazol-5-yl)phenyl]-1 H-indol-4-yl}methyl)-2,6-dimethylmorpholine, compound 1,
      as a novel angiotensin II receptor antagonist is outlined. Radioligand binding
      assays showed that 1 displayed a high affinity for the angiotensin II type
      1receptor with IC50 value of 0.82 nM. It acted as a potent anti-hypertensive
      derivative (maximal reduction of mean arterial pressure of 47 mm Hg at 10 mg/kg
      po in spontaneously hypertensive rat producing a dose-dependent fall in blood
      pressure following oral administration lasting beyond 10 h. Acute toxicity tests
      measured the LD50 of 1 value as 2431.7 mg/kg, which is higher than Losartan
      (LD50=2248 mg/kg). In addition further testing showed that 1 also demonstrated
      efficient anti-proliferative activity in vitro and anti-prostate cancer activity
      in vivo were also found. Taken together this compound could be considered as an
      effective and durable anti-hypertension drug candidate with additional anti
      prostate cancer activity. These encouraging results are deserved of further
      investigation towards its use for therapeutic benefit. 

PMID- 24573982
TI  - Sinovenous thrombosis associated with skull fracture in the setting of blunt head
      trauma.
AB  - BACKGROUND: Emerging literature suggests that closed head injuries may be an
      important etiology of cerebral venous sinus thrombosis (CVST). Fractures over the
      dural sinuses, in particular, may predispose such patients to this secondary
      complication. The purpose of this study was to determine the incidence and
      characteristics of CVST resulting from skull fractures overlying cerebral venous
      sinuses at a single tertiary care center. METHODS: A retrospective review of
      consecutive patients presenting to our institution with skull fractures from
      blunt head trauma between 1 January 2009 and 31 December 2011 who underwent
      either a computed tomography (CT) or magnetic resonance (MR) venogram. Patient
      demographics, associated intracranial injuries, admission Glasgow Coma Scale
      (GCS), presence of CVST, and post-hospital disposition were recorded. RESULTS:
      Overall, 908 patients with skull fractures presented to the institution. Of
      those, 63 had fractures over a sinus and a venogram satisfying inclusion
      criteria. Twenty-two (34.9 %) patients demonstrated a thrombus in at least one
      sinus. There was no statistical difference in patient demographics, presenting
      GCS, length of stay (LOS), or outcome between patients with or without a
      thrombus. Pediatric patients had significantly shorter LOS (11 vs. 4 days, p <
      0.01) compared to adults. Adults had a greater incidence of total sinus
      occlusions while children had more non-occlusive thrombus formations; both were
      statistically significant (p = 0.035 and p = 0.037, respectively). CONCLUSIONS:
      This report suggests that over 10 % of skull fractures involve cerebral venous
      sinuses, thus emphasizing the need to rule out CVST in patients suffering blunt
      head trauma. We propose including a venogram as part of the initial trauma work
      up for these patients. Moreover, our data suggest that pediatric patients may be
      predisposed to less severe injuries than their adult counterparts.

PMID- 24573979
TI  - Comparison of dynamic contrast-enhanced MR, ultrasound and optical imaging
      modalities to evaluate the antiangiogenic effect of PF-03084014 and sunitinib.
AB  - Noninvasive imaging has been widely applied for monitoring antiangiogenesis
      therapy in cancer drug discovery. In this report, we used different imaging
      modalities including high-frequency ultrasound (HFUS), dynamic contrast enhanced
      MR (DCE-MR), and fluorescence molecular tomography (FMT) imaging systems to
      monitor the changes in the tumor vascular properties after treatment with gamma
      secretase inhibitor PF-03084014. Sunitinib was tested in parallel for comparison.
      In the MDA-MB-231Luc model, we demonstrated that antiangiogenesis was one of the
      contributing mechanisms for the therapeutic effect of PF-03084014. By
      immunohistochemistry and FITC-lectin perfusion assays, we showed that the
      vascular defects upon treatment with PF-03084014 were associated with Notch
      pathway modulation, evidenced by a decrease in the HES1 protein and by the
      changes in VEGFR2 and HIF1alpha levels, which indicates down-stream effects.
      Using a 3D power Doppler scanning method, ultrasound imaging showed that the%
      vascularity in the MDA-MB-231Luc tumor decreased significantly at 4 and 7 days
      after the treatment with PF-03084014. A decrease in the tumor vessel function was
      also observed through contrast-enhanced ultrasound imaging with microbubble
      injection. These findings were consistent with the PF-03084014-induced functional
      vessel changes measured by suppressing the K(trans) values using DCE-MRI. In
      contrast, the FMT imaging with the AngioSence 680EX failed to detect any
      treatment-associated tumor vascular changes. Sunitinib demonstrated an outcome
      similar to PF-03084014 in the tested imaging modalities. In summary, ultrasound
      and DCE-MR imaging successfully provided longitudinal measurement of the
      phenotypic and functional changes in tumor vasculature after treatment with PF
      03084014 and sunitinib.

PMID- 24573983
TI  - Staged 'intentional' bridging vein ligation: a safe strategy in gaining wide
      access to skull base tumors.
AB  - BACKGROUND: The venous drainage of the temporal lobe, through bridging veins to
      the middle cranial fossa, is pivotal in determining the surgical corridor for
      skull base lesions. In dealing with select cases, where venous drainage was an
      obstacle in the surgical approach, we hypothesized that staged 'intentional'
      ligation of the dominant pathway of venous drainage would provide a safer and
      wider access to skull base tumors. We study the indications and safety of this
      surgical strategy in the management of skull base lesions. MATERIALS AND METHODS:
      From 1995 to 2012, 318 patients with skull base tumors were treated at our
      institute by the fronto-orbito-zygomatic (FOZ) or transpetrosal approaches, eight
      of whom we planned for staged 'intentional' bridging vein ligation. Seven
      patients underwent planned ligation of the bridging veins from the temporal lobe
      to the middle cranial fossa floor in the first stage, followed by definitive
      surgery through the desired skull base approach, in the second stage, while in
      one patient the strategy was abandoned. These patients were evaluated with
      respect to their clinical presentation, pre- and post-operative radiology
      including venogram, intra-operative findings and post-operative course. RESULTS:
      Seven patients, four males and three females, with ages ranging from 16 to 63
      years, underwent staged 'intentional' bridging vein ligation. The diagnoses were
      recurrent craniopharyngioma in four, and petroclival meningioma,
      sphenopetroclival meningioma and spheno-orbital meningioma in one each. Six of
      these lesions were approached from the dominant (left) side, while one lesion was
      on the right side. Venograms done after the first-stage procedure showed
      obliteration of the dominant venous drainage with opening up of anastomotic
      venous channels in all patients. All patients tolerated the first-stage procedure
      well; only one patient showed asymptomatic mild temporal lobe edema on MRI, which
      resolved in 3 weeks. None of the patients had venous complications after
      definitive surgery. One patient with recurrent chordoma, who was planned for
      staged ligation, did not undergo ligation as, intra-operatively, the draining
      channel turned out to be a cortical vein, which could be mobilized without
      ligation. CONCLUSION: In an attempt to detether the temporal lobe, the
      disconnection of the bridging veins from the temporal lobe to the middle cranial
      fossa floor in the first stage may lead to re-direction of the venous outflow
      over time. This may allow skull base surgeons a better surgical corridor and
      ensure safety of venous structures during the definitive surgery.

PMID- 24573984
TI  - Identification of predictive factors for response to intravenous immunoglobulin
      treatment in children with immune thrombocytopenia.
AB  - Acute immune thrombocytopenia (ITP) is a common benign bleeding disorder of
      variable etiology characterized by isolated thrombocytopenia. Intravenous
      immunoglobulin (IVIG) treatment is generally given as an initial treatment to
      pediatric patients with ITP, but markers predictive of the response to IVIG
      remain poorly defined. We retrospectively evaluated whether clinical and
      laboratory findings before treatment could predict response to IVIG and
      progression to chronic ITP in Japanese children with ITP. Between April 1997 and
      December 2011, a total of 49 children with newly diagnosed ITP were initially
      treated with IVIG. Their medical records were retrospectively reviewed. In
      multivariate analyses, lower white blood cell (WBC) count was the only
      unfavorable factor for response to IVIG and progression to chronic ITP. Patients
      with WBC count <7.0 * 10(9)/L had a lower probability of thrombocytopenia-free
      survival (41 vs. 77 %, P = 0.003) and a higher rate of progression to chronic ITP
      (29 vs. 6 %, P = 0.040) than those with WBC count >=7.0 * 10(9)/L. These results
      suggest that ITP with lower WBC count may represent a distinct subgroup requiring
      initial treatment other than IVIG.

PMID- 24573985
TI  - Proton conductivity in doped aluminum phosphonate sponges.
AB  - Proton-conducting networks (NETs) were prepared successfully by the insertion of
      phosphonated nanochannels into organic-inorganic hybrid materials that contain
      Al(3+) as the connector and hexakis(p-phosphonatophenyl)benzene (HPB) as the
      linker. Noncomplexed phosphonic acid groups remain in the framework, which
      depends on the ratio of both compounds, to yield a proton conductivity in the
      region of 10(-3) S cm(-1). This conductivity can be further improved and values
      as high as Nafion, a benchmark proton-exchange membrane for fuel cell
      applications, can be obtained by filling the network pores with intrinsic proton
      conductors. As a result of their sponge-like morphology, aluminum phosphonates
      adsorb conductive small molecules such as phosphonic acids, which results in a
      very high proton conductivity of approximately 5 * 10(-2) S cm(-1) at 120 
      degrees C and 50 % relative humidity (RH). Contrary to Nafion, the doped networks
      show a remarkably low temperature dependence of proton conductivity from external
      humidification. This effect indicates a transport mechanism that is different to
      the water vehicle mechanism. Furthermore, the materials exhibit an activation
      energy of 40 kJ mol(-1) at 15 % RH that starts to diminish to 10 kJ mol(-1) at 80
      % RH, which is even smaller than the corresponding values obtained for Nafion
      117.

PMID- 24573986
TI  - Toxoplasma gondii infection of decidual CD1c(+) dendritic cells enhances
      cytotoxicity of decidual natural killer cells.
AB  - There is crosstalk between decidual natural killer (dNK) cells and decidual
      dendritic cells (dDCs) that promotes tolerance of trophoblast cells carrying
      paternally derived antigens. In the present study, we report that infection of
      CD1c(+) dDCs with Toxoplasma gondii enhanced gamma interferon (IFN-gamma)
      production by dNK cells in co-culture. The enhancement of IFN-gamma production
      was induced by cytokine IL-12 which increased obviously in co-culture of dDCs
      with dNK cells following T. gondii infection, and this enhancement largely
      abrogated when cells were cultured in the presence of an anti-IL-12 antibody. The
      expression of KIR2DL4 and NKG2D on dNK cells was increased after T. gondii
      infection, and higher expression of NKG2D was induced by co-cultured dDCs.
      Neutralization of IL-12 decreased NKG2D expression on dNK cells. Furthermore,
      dDCs with T. gondii infection increased the cytotoxicity of co-cultured dNK cells
      against K562 target cells, which was mediated by activating receptor of NKG2D.
      Thus, T. gondii infection of dDCs enhanced dNK cell IFN-gamma production and
      NKG2D expression, and then led to increased cytotoxicity of dNK cells. The up
      regulated dNK cell cytotoxicity at the maternal-fetal interface may contribute to
      abnormal pregnancy outcomes caused by T. gondii infection in early pregnancy. 

PMID- 24573987
TI  - Soluble thrombomodulin to evaluate the severity and outcome of community-acquired
      pneumonia.
AB  - This study aims to investigate the role of soluble thrombomodulin (sTM) in the
      evaluation of the severity and outcome of community-acquired pneumonia (CAP) in
      the emergency department (ED) and compare sTM with two biomarkers-procalcitonin
      (PCT) and C-reactive protein (CRP)-and two scoring systems-the Pneumonia Severity
      Index (PSI) and CURB65 score. Patients with CAP were consecutively enrolled in
      the ED of an urban university hospital. sTM, PCT, and CRP levels were measured on
      enrollment. In addition, the PSI and CURB65 scores were calculated. For all
      patients, a 30-day follow-up was performed. A total of 573 patients with CAP were
      enrolled in this study. sTM, PCT, and CRP levels increased with the aggravation
      of the disease severity as assessed by the PSI and CURB65 score (all P <0.01).
      The multivariate logistic regression analysis showed that sTM and the PSI were
      independent predictors of 30-day mortality, and the receiver operating
      characteristic curve analysis showed that the accuracy of sTM in the prediction
      of 30-day mortality was comparable with the PSI (P >0.05) and better than PCT,
      CRP, and the CURB65 score (P all <0.05). Furthermore, a combination of sTM and
      scoring systems can enhance the predictive accuracy of 30-day mortality. sTM is
      useful in the evaluation of the severity and outcome of CAP in the ED. A well
      designed, multi-center study will be needed to further investigate the value of
      sTM in CAP.

PMID- 24573988
TI  - Modification of biomaterials with a self-protein inhibits the macrophage
      response.
AB  - A biomaterial inhibits the host immune response by displaying an endo-genously
      expressed immunomodulatory molecule, CD200. Immobilization of CD200 onto
      biomaterial surfaces effectively suppresses macrophage activation and reduces
      inflammatory response to subcutaneously implanted materials. 

PMID- 24573995
TI  - Supramolecular assemblies by charge-transfer interactions between donor and
      acceptor chromophores.
AB  - We have collated various supramolecular designs that utilize organic donor
      acceptor CT complexation to generate noncovalently co-assembled structures
      including fibrillar gels, micelles, vesicles, nanotubes, foldamers,
      conformationally restricted macromolecules, and liquid crystalline phases.
      Possibly inspired by nature, chemists have extensively used hydrogen bonding as a
      tool for supramolecular assemblies of a diverse range of abiotic building blocks.
      As a structural motif, CT complexes can be compared to hydrogen-bonded complexes
      in its directional nature and complementarities. Additional advantages of CT
      interactions include wider solvent tolerance and easy spectroscopic probing.
      Nevertheless the major limitation is their low association constant. This article
      shows different strategies have evolved over the years to overcome this drawback
      by reinforcing the CT interactions with auxiliary noncovalent forces without
      hampering the alternate stacking mode. Emerging reports on promising CT complexes
      in organic electronics are intimately related to various supramolecular designs
      that one can postulate based on donor-acceptor CT interactions. 

PMID- 24573992
TI  - Highly efficient respiratory motion compensated free-breathing coronary MRA using
      golden-step Cartesian acquisition.
AB  - PURPOSE: To develop an efficient 3D affine respiratory motion compensation
      framework for Cartesian whole-heart coronary magnetic resonance angiography
      (MRA). MATERIALS AND METHODS: The proposed method achieves 100% scan efficiency
      by estimating the affine respiratory motion from the data itself and correcting
      the acquired data in the reconstruction process. For this, a golden-step
      Cartesian sampling with spiral profile ordering was performed to enable
      reconstruction of respiratory resolved images at any breathing position and with
      different respiratory window size. Affine motion parameters were estimated from
      image-based registration of 3D undersampled respiratory resolved images
      reconstructed with iterative SENSE and motion correction was performed directly
      in the reconstruction using a multiple-coils generalized matrix formulation
      method. This approach was tested on healthy volunteers and compared against a
      conventional diaphragmatic navigator-gated acquisition using quantitative and
      qualitative image quality assessment. RESULTS: The proposed approach achieved 47
      +/- 12% and 59 +/- 6% vessel sharpness for the right (RCA) and left (LAD)
      coronary arteries, respectively. Also, good quality visual scores of 2.4 +/- 0.74
      and 2.44 +/- 0.86 were observed for the RCA and LAD (scores from 0, no to 4,
      excellent coronary vessel delineation). A not statically significant difference
      (P = 0.05) was found between the proposed method and an 8-mm navigator-gated and
      tracked scan, although scan efficiency increased from 61 +/- 10% to 100%.
      CONCLUSION: We demonstrate the feasibility of a new 3D affine respiratory motion
      correction technique for Cartesian whole-heart CMRA that achieves 100% scan
      efficiency and therefore a predictable acquisition time. This approach yields
      image quality comparable to that of an 8-mm navigator-gated acquisition with
      lower scan efficiency. Further evaluation of this technique in patients is now
      warranted to determine its clinical use.

PMID- 24573996
TI  - Regulation of the cyanobacterial circadian clock by electrochemically controlled
      extracellular electron transfer.
AB  - There is growing awareness that circadian clocks are closely related to the
      intracellular redox state across a range of species. As the redox state is
      determined by the exchange of the redox species, electrochemically controlled
      extracellular electron transfer (EC-EET), a process in which intracellular
      electrons are exchanged with extracellular electrodes, is a promising approach
      for the external regulation of circadian clocks. Herein, we discuss whether the
      circadian clock can be regulated by EC-EET using the cyanobacterium Synechococcus
      elongatus PCC7942 as a model system. In vivo monitoring of chlorophyll
      fluorescence revealed that the redox state of the plastoquionone pool could be
      controlled with EC-EET by simply changing the electrode potential. As a result,
      the endogenous circadian clock of S. elongatus cells was successfully entrained
      through periodically modulated EC-EET by emulating the natural light/dark cycle,
      even under constant illumination conditions. This is the first example of
      regulating the biological clock by electrochemistry. 

PMID- 24573999
TI  - Association between ACE I/D polymorphism and pulmonary tuberculosis in Chinese
      population.
AB  - Tuberculosis (TB) remains a global public health problem worldwide. The objective
      of the current study is to investigate the possible association of ACE I/D
      polymorphism with pulmonary TB (PTB) for Chinese in Sichuan province. Three
      hundred eighty-six PTB patients and 398 healthy controls were genotyped to
      analyze the I/D polymorphism using PCR method. The results showed that the I/D
      polymorphism was not associated with susceptibility to PTB for Chinese (D vs. I:
      OR 1.03, 95% CI 0.84-1.26, and P=0.77; DD vs. II+DI: OR 1.09, 95% CI 0.73-1.63,
      and P=0.68; DD+DI vs. II: OR 1.00, 95% CI 0.74-1.33, and P=0.98). The I/D
      polymorphism in the ACE gene may not a risk factor for PTB in Chinese.

PMID- 24573998
TI  - Endothelial nitric oxide (eNOS) gene G894T and VNTR polymorphisms are closely
      associated with the risk of ischemic stroke development for Asians: meta-analysis
      of epidemiological studies.
AB  - Although the relationships between endothelial nitric oxide synthase (eNOS) gene
      polymorphisms (including G894T, VNTR and T786C) and risk of ischemic stroke (IS)
      have been extensively studied, controversial results have been reported. The aim
      of this study was to assess the relationships between them by using a meta
      analysis. Literatures were retrieved through the following databases: Medline,
      Embase and Wangfang (updated to January 1st, 2013). Fixed- or random-effects
      model was used to calculate pooled odds ratio and 95 % confidence interval (OR
      and 95 % CI). A total of 31 case-control studies including 8,547 patients and
      9,117 controls were included in this meta-analysis eventually. For eNOS G894T
      polymorphism, the results indicated that TT genotype was significantly associated
      with increased risk of IS incidence compared to G allele (OR and 95 % CI 1.25
      (1.09-1.42) for TT vs. GT+GG, P < 0.001). When subgroup analysis was conducted
      according to ethnicities, T allele was significantly associated with risk of IS
      for Asians rather than for Caucasians. For eNOS VNTR polymorphism, 4aa genotype
      was significantly associated with risk of IS incidence compared to 4bb genotype
      (OR (95 % CI) 2.22 (1.66-2.97) for aa vs. bb, P < 0.001). Similarly, when
      subgroup analyses were conducted, 4aa was closely associated with increased risk
      of IS for Asians rather than for Caucasians. For eNOS T786C polymorphism, it was
      not associated with risk of IS incidence. In conclusion, this study indicated
      that eNOS 894T and VNTR 4a allele was significantly associated with risk of IS
      incidence for Asians. However, eNOS T786C polymorphism was not a likely risk
      factor for IS incidence.

PMID- 24574000
TI  - Transcription factor 7-like 2 (TCF7L2) gene polymorphism and clinical phenotype
      in end-stage renal disease patients.
AB  - Variants of the transcription factor 7-like 2 gene (TCF7L2) have been associated
      with type 2 diabetes and cardiovascular disease in different populations. Here we
      investigated the potential association of the rs7903146 polymorphism in the
      TCF7L2 gene with clinical profile of end-stage renal disease (ESRD) patients. We
      examined a cohort of 1065 ESRD patients with diabetic and non-diabetic renal
      disease. The control group consisted of 924 healthy individuals. All subjects
      were genotyped for the rs7903146 single nucleotide polymorphism by polymerase
      chain reaction. The genotype distribution and allele frequencies were
      significantly different between ESRD patients and controls (p < 0.01). The OR for
      the TT genotype was 2.81 (95% CI 2.08-3.79). Genotype and allele frequencies were
      compared between subgroups of patients with different clinical phenotypes. The
      frequency of the T allele was significantly higher in patients with diabetic
      nephropathy versus non-diabetic renal disease (p = 0.007, OR 1.70, 95% CI 1.36
      2.11). The statistically significant differences were demonstrated between
      patients with and without cardiovascular disease, with the OR for T allele 1.57
      (95% CI 1.31-1.90). The odds ratio for TT genotype was 2.38 (95% CI 1.62-3.51).
      In our study the T allele of the rs7903146 SNP in the TCF7L2 gene confers the
      risk of developing diabetic nephropathy. We described for the first time a strong
      relationship between the TCF7L2 gene variant rs7903146 and cardiovascular disease
      in end-stage renal disease patients.

PMID- 24574001
TI  - Ellagic acid inhibits PKC signaling by improving antioxidant defense system in
      murine T cell lymphoma.
AB  - Antioxidants protect the cells from the damaging effects of reactive oxygen
      species (ROS). Production of ROS during cellular metabolism is balanced by their
      removal by antioxidants. Any condition leading to increased levels of ROS results
      in oxidative stress, which participates in multistage carcinogenesis by causing
      oxidative DNA damage, mutations in the proto-oncogenes and tumor suppressor
      genes. Antioxidant defense system is required to overcome the process of
      carcinogenesis generated by ROS. Antioxidant enzymes are major contributors to
      endogenous antioxidant defense system. Protein kinase C (PKC) is generally
      involved in cell proliferation and its over expression leads to abnormal tumor
      growth. Out of three classes of PKC, classical PKC is mainly involved in cell
      proliferation and tumor growth. Classical PKC initiates signaling pathway and
      leads to activation of a number of downstream protein via activation of NF
      kappaB. Therefore any agent which can promotes the endogenous antioxidant defense
      system should be able to down regulate PKC and NF-kappaB activation and thus may
      be useful in reducing cancer progression. To investigate this hypothesis we have
      tested the effect of antioxidant ellagic acid on antioxidant enzymes and PKC
      signaling in Dalton's lymphoma bearing (DL) mice. DL mice were treated with three
      different doses of ellagic acid. The treatment significantly increases the
      activity and expression of antioxidant enzymes and down regulates the expression
      of classical isozymes of PKC as well as the activation of NF-kappaB, indicating
      that ellagic acid improves antioxidant defense system and PKC signaling via NF
      kappaB which may contribute to its cancer preventive role. 

PMID- 24574002
TI  - Structure and dynamics studies of sterol 24-C-methyltransferase with mechanism
      based inactivators for the disruption of ergosterol biosynthesis.
AB  - The enzyme sterol 24-C-methyltransferase (SMT) belongs to the family of
      transferases, specifically to the one-carbon transferring methyltransferases. SMT
      has been found playing a major role during the production of steroids, especially
      for the biosynthesis of ergosterol, which is the major membrane sterol in
      leishmania parasites, causing leishmaniasis. However, SMT and ergosterol are not
      found in mammals, so, an extensive study has been carried out over the
      susceptible SMT protein, which is found to be highly conserved among all the
      Leishmania species and holds a significant anti-leishmanial drug target. To date,
      there is no computational data available for SMT, due to its highly unexplored
      profile. In this work, a complete set of structural attributes have been examined
      through the available computational procedures, along with an attempt to
      characterize the most capable modeling server available. The exploration ranges
      from physicochemical characterization, pairwise alignment, secondary structure
      prediction, to active site detection. With this information, a docking study was
      carried out to find the compound that best binds into the active site. Moreover,
      molecular dynamics simulation was conducted to examine the stability of the
      homology modeled protein and the ligand-enzyme complex. The results indicate that
      the ligand-enzyme complex is more stable. 

PMID- 24574003
TI  - RNAi Mediated curcin precursor gene silencing in Jatropha (Jatropha curcas L.).
AB  - Curcin, a type I ribosomal inhibiting protein-RIP, encoded by curcin precursor
      gene, is a phytotoxin present in Jatropha (Jatropha curcas L.). Here, we report
      designing of RNAi construct for the curcin precursor gene and further its genetic
      transformation of Jatropha to reduce its transcript expression. Curcin precursor
      gene was first cloned from Jatropha strain DARL-2 and part of the gene sequence
      was cloned in sense and antisense orientation separated by an intron sequence in
      plant expression binary vector pRI101 AN. The construction of the RNAi vector was
      confirmed by double digestion and nucleotide sequencing. The vector was then
      mobilized into Agrobacterium tumefaciens strain GV 3101 and used for tissue
      culture independent in planta transformation protocol optimized for Jatropha.
      Germinating seeds were injured with a needle before infection with Agrobacterium
      and then transferred to sterilized sand medium. The seedlings were grown for 90
      days and genomic DNA was isolated from leaves for transgenic confirmation based
      on real time PCR with NPT II specific dual labeled probe. Result of the
      transgenic confirmation analysis revealed presence of the gene silencing
      construct in ten out of 30 tested seedlings. Further, quantitative transcript
      expression analysis of the curcin precursor gene revealed reduction in the
      transcript abundance by more than 98% to undetectable level. The transgenic
      plants are being grown in containment for further studies on reduction in curcin
      protein content in Jatropha seeds.

PMID- 24574004
TI  - A man with low cholesterol and weakness of the lower limbs.

PMID- 24573997
TI  - Pharmacological approaches to reducing craving in patients with alcohol use
      disorders.
AB  - Research on the concept of craving may lead to better understanding of the
      biobehavioural circuitries that contribute to the complexity of alcohol use
      disorders (AUDs). The experiences described as craving or desire to drink are
      often associated with physical responses such as increased salivation and heart
      rate, and alteration of stress hormones, as well as psychological responses such
      as anxiety and depression. Greater craving has been associated with an increased
      probability of alcohol relapse. Reversal of craving, which is understood as a
      symptom of protracted abstinence, offers the possibility of preventing relapses
      and treating alcoholism. Various medications have been studied to establish
      whether they are able to reduce craving; however, the results obtained from
      clinical studies have been inconsistent. Here, we review the interdisciplinary
      models developed to evaluate craving, then the different approaches used to
      assess and measure craving and, finally, the medications utilized and tested to
      lessen craving in patients suffering from AUDs. 

PMID- 24574005
TI  - A man with two syndromes.

PMID- 24574006
TI  - Nitrogen-doped graphene/carbon nanotube hybrids: in situ formation on
      bifunctional catalysts and their superior electrocatalytic activity for oxygen
      evolution/reduction reaction.
AB  - There is a growing interest in oxygen electrode catalysts for oxygen reduction
      reaction (ORR) and oxygen evolution reaction (OER), as they play a key role in a
      wide range of renewable energy technologies such as fuel cells, metal-air
      batteries, and water splitting. Nevertheless, the development of highly-active
      bifunctional catalysts at low cost for both ORR and OER still remains a huge
      challenge. Herein, we report a new N-doped graphene/single-walled carbon nanotube
      (SWCNT) hybrid (NGSH) material as an efficient noble-metal-free bifunctional
      electrocatalyst for both ORR and OER. NGSHs were fabricated by in situ doping
      during chemical vapor deposition growth on layered double hydroxide derived
      bifunctional catalysts. Our one-step approach not only provides simultaneous
      growth of graphene and SWCNTs, leading to the formation of three dimensional
      interconnected network, but also brings the intrinsic dispersion of graphene and
      carbon nanotubes and the dispersion of N-containing functional groups within a
      highly conductive scaffold. Thus, the NGSHs possess a large specific surface area
      of 812.9 m(2) g(-1) and high electrical conductivity of 53.8 S cm(-1) . Despite
      of relatively low nitrogen content (0.53 at%), the NGSHs demonstrate a high ORR
      activity, much superior to two constituent components and even comparable to the
      commercial 20 wt% Pt/C catalysts with much better durability and resistance to
      crossover effect. The same hybrid material also presents high catalytic activity
      towards OER, rendering them high-performance cheap catalysts for both ORR and
      OER. Our result opens up new avenues for energy conversion technologies based on
      earth-abundant, scalable, noble-metal-free catalysts. 

PMID- 24574007
TI  - Preclinical cadaveric study of transanal robotic proctectomy with total
      mesorectal excision combined with laparoscopic assistance.
AB  - BACKGROUND: Anterior resection with total mesorectal excision (TME) is the
      standard method of rectal cancer resection. However, this procedure remains
      technically difficult. A robotic transanal approach could overcome some of these
      limitations. An initial laboratory experience with robotic transanal TME using a
      new designed port on human cadavers is reported. METHODS: The feasibility of
      robotic transanal TME and ideal set-up were evaluated in human cadavers. For the
      da Vinci Si HD system transanal access and total mesorectal excision, a
      specifically designed port was used. RESULTS: It was possible to complete a
      proctectomy with transanal total mesorectal excision. The port proved to be very
      reliable and facilitated docking of the robotic arms. CONCLUSION: Using the
      robotic technology and a specifically designed port for robotic transanal access,
      TME was shown to be feasible and one specific preferred set-up was determined.
      Further clinical trials will be necessary to assess the safety and efficacy of
      this technique.

PMID- 24574012
TI  - Makoplasty and the accuracy and efficacy of robotic-assisted arthroplasty.
AB  - In comparison with standard surgical techniques robotic-assisted surgery has the
      advantages of increased surgical accuracy, reproducibility, optimization of
      component position, and improved patient outcomes in unicompartmental knee
      arthroplasty (UKA) and total hip arthoplasty (THA) procedures. The MAKO Tactile
      Guidance System (TGS; MAKO Surgical Corp, Fort Lauderdale, FL) facilitates
      robotic-assisted arthroplasty procedures currently implemented in many operating
      rooms. The benefits of this technology are evident, but have not been shown to
      improve patient outcomes and justify the added financial burden imposed. Further
      research is needed to determine if this technological advancement will translate
      into improvements in longevity and clinical outcomes. 

PMID- 24574011
TI  - Simulation study comparing the effectiveness of the Gynecare Morcellex(r), the
      MOREsolutionTM, and the RotocutTM G1 tissue Morcellators.
AB  - Laparoscopic surgery has revolutionized the manner in which many operations are
      performed today. The volume of tissue to be removed during some operations can be
      a limiting factor for laparoscopy and is frequently a reason for converting from
      a minimally invasive laparoscopic surgical approach to the conventional open
      surgical approach. The introduction of the electronic morcellator has helped
      facilitate the removal of large specimens via minimally invasive surgery. The
      purpose of this study is to evaluate the effectiveness of the Gynecare
      Morcellex(r) morcellator (Ethicon, Inc., Somerville, NJ), the MOREsolutionTM
      morcellator (Blue Endo, Lenexa, Kansas), and the RotocutTM G1 morcellator (Karl
      Storz, Tuttlingen, Germany) tissue morcellators based upon their ease of use and
      efficacy in a simulation setting among an unbiased cohort of novice surgeons.
      University of Central Florida College of Medicine students were observed using
      the three different morcellators in a randomized order on 250 g beef tissue
      models and were surveyed on the ease of use of the morcellators. The
      MOREsolutionTM tissue morcellator demonstrated significantly faster tissue
      morcellation times (544.6 +/- 123.0 sec) and produced a higher number of long
      tissue fragments (7.44 +/- 0.683) compared to the RotocutTM G1 morcellators' time
      (609.7 +/- 153.2 sec) and number of long tissue fragments (6.00 +/- 0.638). No
      significant differences were found between the Gynecare Morcellex(r) and other
      morcellators in the total number of fragments obtained nor study participant
      opinion on the ease of use of the three morcellators. This study demonstrates
      that the MOREsolutionTM morcellator is a faster morcellator and produces larger
      tissue fragments as compared to the RotocutTM G1; however, more studies should be
      performed to confirm these findings in a clinical setting. 

PMID- 24574008
TI  - Vascular endothelial growth factor coordinates islet innervation via vascular
      scaffolding.
AB  - Neurovascular alignment is a common anatomical feature of organs, but the
      mechanisms leading to this arrangement are incompletely understood. Here, we show
      that vascular endothelial growth factor (VEGF) signaling profoundly affects both
      vascularization and innervation of the pancreatic islet. In mature islets, nerves
      are closely associated with capillaries, but the islet vascularization process
      during embryonic organogenesis significantly precedes islet innervation. Although
      a simple neuronal meshwork interconnects the developing islet clusters as they
      begin to form at E14.5, the substantial ingrowth of nerve fibers into islets
      occurs postnatally, when islet vascularization is already complete. Using genetic
      mouse models, we demonstrate that VEGF regulates islet innervation indirectly
      through its effects on intra-islet endothelial cells. Our data indicate that
      formation of a VEGF-directed, intra-islet vascular plexus is required for
      development of islet innervation, and that VEGF-induced islet
      hypervascularization leads to increased nerve fiber ingrowth. Transcriptome
      analysis of hypervascularized islets revealed an increased expression of
      extracellular matrix components and axon guidance molecules, with these
      transcripts being enriched in the islet-derived endothelial cell population. We
      propose a mechanism for coordinated neurovascular development within pancreatic
      islets, in which endocrine cell-derived VEGF directs the patterning of intra
      islet capillaries during embryogenesis, forming a scaffold for the postnatal
      ingrowth of essential autonomic nerve fibers.

PMID- 24574013
TI  - DIY 3D printing of custom orthopaedic implants: a proof of concept study.
AB  - 3D printing is an emerging technology that is primarily used for aiding the
      design and prototyping of implants. As this technology has evolved it has now
      become possible to produce functional and definitive implants manufactured using
      a 3D printing process. This process, however, previously required a large
      financial investment in complex machinery and professionals skilled in 3D product
      design. Our pilot study's aim was to design and create a 3D printed custom
      orthopaedic implant using only freely available consumer hardware and software. 

PMID- 24574010
TI  - Ubpy controls the stability of the ESCRT-0 subunit Hrs in development.
AB  - Ubiquitylated developmental membrane signaling proteins are often internalized
      for endocytic trafficking, through which endosomal sorting complexes required for
      transport (ESCRT) act sequentially to deliver internalized cargos to lysosomes.
      The ESCRT function in endocytic sorting is well established; however, it is not
      fully understood how the sorting machinery itself is regulated. Here, we show
      that Ubiquitin isopeptidase Y (Ubpy) plays a conserved role in vivo in the
      homeostasis of an essential ESCRT-0 complex component Hrs. We find that, in the
      absence of Drosophila Ubpy, multiple membrane proteins that are essential
      components of important signaling pathways accumulate in enlarged, aberrant
      endosomes. We further demonstrate that this phenotype results from endocytic
      pathway defects. We provide evidence that Ubpy interacts with and deubiquitylates
      Hrs. In Ubpy-null cells, Hrs becomes ubiquitylated and degraded in lysosomes,
      thus disrupting the integrity of ESCRT sorting machinery. Lastly, we find that
      signaling proteins are enriched in enlarged endosomes when Hrs activity is
      abolished. Together, our data support a model in which Ubpy plays a dual role in
      both cargo deubiquitylation and the ESCRT-0 stability during development.

PMID- 24574009
TI  - Hox proteins drive cell segregation and non-autonomous apical remodelling during
      hindbrain segmentation.
AB  - Hox genes encode a conserved family of homeodomain transcription factors
      regulating development along the major body axis. During embryogenesis, Hox
      proteins are expressed in segment-specific patterns and control numerous
      different segment-specific cell fates. It has been unclear, however, whether Hox
      proteins drive the epithelial cell segregation mechanism that is thought to
      initiate the segmentation process. Here, we investigate the role of vertebrate
      Hox proteins during the partitioning of the developing hindbrain into lineage
      restricted units called rhombomeres. Loss-of-function mutants and ectopic
      expression assays reveal that Hoxb4 and its paralogue Hoxd4 are necessary and
      sufficient for cell segregation, and for the most caudal rhombomere boundary
      (r6/r7). Hox4 proteins regulate Eph/ephrins and other cell-surface proteins, and
      can function in a non-cell-autonomous manner to induce apical cell enlargement on
      both sides of their expression border. Similarly, other Hox proteins expressed at
      more rostral rhombomere interfaces can also regulate Eph/ephrins, induce apical
      remodelling and drive cell segregation in ectopic expression assays. However,
      Krox20, a key segmentation factor expressed in odd rhombomeres (r3 and r5), can
      largely override Hox proteins at the level of regulation of a cell surface
      target, Epha4. This study suggests that most, if not all, Hox proteins share a
      common potential to induce cell segregation but in some contexts this is masked
      or modulated by other transcription factors.

PMID- 24574014
TI  - Negative pressure wound therapy with instillation: the current state of the art.
AB  - Traditional negative pressure wound therapy (NPWT) has revolutionized the
      treatment of complex wounds for nearly 20 years. A decade ago, a modification of
      the original system added intermittent automated instillation of topical wound
      irrigation solutions to traditional negative pressure wound therapy. This
      combined therapy, termed negative pressure wound therapy with instillation
      (NPWTi), has been shown to be effective in the treatment of a variety of complex
      wounds. Negative pressure wound therapy with instillation has been shown to
      reduce bioburden and biofilms present in wounds helping heal clinically infected
      wounds. It has also been used with success to jump-start stalled wounds, in
      relieving wound pain and treating infected foreign bodies including infected
      orthopedic hardware and some types of exposed abdominal wall mesh. The system
      includes a foam dressing placed in the wound covered by a semi-occlusive drape. A
      tubing placed over a hole cut in the drape connects the foam dressing to a pump
      run by a computerized microprocessor that delivers negative pressure to the
      dressing and wound. A preset volume of instillation fluid is automatically
      delivered via the instillation tubing to the wound. The fluid is held in the foam
      to bathe the wound for a predetermined time period. Negative pressure is then re
      started draining the irrigation fluid and any wound exudate into a collection
      canister. The entire sequence is automated and consists of three phases: (1)
      fluid instillation; (2) holding for a period of time in the wound, which is fully
      expanded since the negative pressure is off during this phase; and then (3) a
      cycle of continuous negative pressure. The entire sequence repeats itself
      automatically. Typically the dressing is changed three times a week. The
      variables involved in treating patients with negative pressure wound therapy with
      instillation included: the indicated wound types; the system settings; the choice
      of the irrigation solution and the duration of therapy. This article will serve
      as a reference to help the negative through treating patients with NPWTi from
      patient selection, system setting to the complication of therapy.

PMID- 24574015
TI  - Prospective Analysis of Laparoscopic Ventral Hernia Repair Using the
      VentralightTM ST Hernia Patch With or Without the ECHO PSTM Positioning System.
AB  - The purpose of the current prospective study was to confirm the results of our
      previous study on the use of the VentralightTM ST mesh. In this study we also
      evaluated a pre-attached positioning system. Between July 2011 and October 2013
      prospectively collected data of 61 consecutive patients who underwent a
      laparoscopic ventral hernia repair were analyzed. Short- and long-term outcomes
      were described. A total of 61 patients were treated in this period (men/women
      ratio 44/17). Overall median follow-up was 7 months (range 2-29). There were 30
      patients with a follow-up of at least 12 months. Mean hernia diameter was 6 x 5
      cm (craniocaudal x laterolateral) (range 1.5 x 1.5 to 20 x 15 cm). Overall mean
      length of hospital stay was 4.4 days. Postoperative visual analog scale (VAS) at
      last follow-up was significantly lower than the preoperative VAS (3.01 vs 0.68; P
      = 0.011) There were no intraoperative complications. In the whole group, only 6
      patients (10%) showed minor complications. Four patients had mild discomfort,
      another 2 patients developed a clinically significant seroma. The complication
      rate in the subgroup with a follow-up of at least 1 year was 13%. No recurrences
      were observed. This study confirms our preliminary findings on the use of this
      mesh. The optional positioning system offers a significantly more quick and
      proper mesh positioning.

PMID- 24574016
TI  - Innovations in hip arthroplasty three-dimensional modeling and analytical
      technology (SOMA).
AB  - The modern generations of cementless hip arthroplasty implant designs are based
      on precise fit and fill of components within the native bony geometry of the
      proximal femur and the acetabulum for enhanced implant longevity. Variations
      exist based on a number of population demographics such as age, gender, body mass
      index, and ethnicity. Recently, establishment of comprehensive electronic
      computerized tomographic databases from a diverse population worldwide have been
      key innovations in the field of implant development. This technology provides a
      potential improvement compared to historical techniques of implant design and
      manufacturing which involved limited trials on cadavers. Segmentation of the
      computerized data to generate three-dimensional models allows precise and
      accurate measurements of anatomical structures and may provide better
      understanding of anthropometric variations that occur among individuals. Evidence
      and population-based computational analyses may provide a better tool for
      designing orthopaedic implants that deliver an enhanced fit for a more diverse
      patient population. Moreover, these population-based databases can also verify
      new designs by means of virtual implantation and analysis on specific or large
      groups of bones within the database. The aim of this paper is to describe a three
      dimensional modeling and analytical technology and to review the various
      applications of this technology in relation to hip arthroplasty. 

PMID- 24574017
TI  - Systematic review and meta-analysis of closed suction drainage versus non
      drainage in primary hip arthroplasty.
AB  - The routine use of drains in surgery has been dogmatically instituted in some
      disciplines. Orthopaedic surgery is one such sub-speciality. The use of
      postoperative closed suction drainage in total hip arthroplasty (THA) has become
      increasingly controversial with multiple randomised control trials performed to
      assess the benefit to outcome in THA. The hypothesis of this systematic review is
      that closed suction drainage does not infer a benefit and increase transfusion
      requirements of primary total hip arthroplasty patients. A systematic review and
      meta-analysis was conducted adhering to the PRISMA guidelines. A search of the
      available literature was performed on PubMed, Cochrane Central Registry of
      Controlled Trials, MEDLINE (OVID) and EMBASE using a combination of MeSH terms
      and Boolean operators. All data analysis was performed using the Cochrane
      Collaboration's Review Manager 5.1. Sixteen studies (n=2705) were included in the
      analysis. Post-operative closed suction drainage was found to increase total
      blood loss and blood transfusion requirements (p<0.05). Surgical site infection
      demonstrated no significant difference between the two groups (p=0.82). No
      significant difference in haematoma formation between groups (p=0.19) was
      elicited. The routine use of closed suction drainage systems post primary hip
      arthroplasty is not supported by this meta-analysis. However, the heterogeneity
      between studies does limit the accuracy of the meta-analysis. 

PMID- 24574018
TI  - Prospective analysis of laparoscopic ventral hernia repair using the
      VentralightTM ST hernia patch with or without the ECHO PSTM positioning system.
AB  - The purpose of the current prospective study was to confirm the results of our
      previous study on the use of the VentralightTM ST mesh. In this study we also
      evaluated a pre-attached positioning system. Between July 2011 and October 2013
      prospectively collected data of 61 consecutive patients who underwent a
      laparoscopic ventral hernia repair were analyzed. Short- and long-term outcomes
      were described. A total of 61 patients were treated in this period (men/women
      ratio 44/17). Overall median follow-up was 7 months (range 2-29). There were 30
      patients with a follow-up of at least 12 months. Mean hernia diameter was 6 x 5
      cm (craniocaudal x laterolateral) (range 1.5 x 1.5 to 20 x 15 cm). Overall mean
      length of hospital stay was 4.4 days. Postoperative visual analog scale (VAS) at
      last follow-up was significantly lower than the preoperative VAS (3.01 vs 0.68; P
      = 0.011) There were no intraoperative complications. In the whole group, only 6
      patients (10%) showed minor complications. Four patients had mild discomfort,
      another 2 patients developed a clinically significant seroma. The complication
      rate in the subgroup with a follow-up of at least 1 year was 13%. No recurrences
      were observed. This study confirms our preliminary findings on the use of this
      mesh. The optional positioning system offers a significantly more quick and
      proper mesh positioning. 

PMID- 24574019
TI  - A prospective study of one-year clinical outcomes utilizing a composite three
      dimensional device with a tissue-separating layer for repair of primary ventral
      and small incisional hernia.
AB  - Primary ventral and even small incisional hernias have historically been repaired
      by primary closure; however, data proves that use of mesh can significantly
      reduce hernia recurrence. Here we report clinical outcomes at one year using the
      International Hernia Mesh Registry following the use of a three-dimensional
      tissue-separating mesh device (Proceed Ventral PatchTM, Ethicon, Somerville, NJ).
      This ongoing prospective multi-center registry collects preoperative,
      perioperative, and postoperative outcome data including adverse events at 1, 6,
      12, and 24 months. Patient-reported outcomes are collected including a hernia
      specific questionnaire. A total of 234 patients (72.1% male, 27.9% female) from
      13 sites in the United States and Europe were enrolled. Mean age and BMI were
      52.2 (SD 15.0) and 29.2 kg/m2 (SD 5.2), respectively. Hernia types: umbilical
      67.1%, epigastric 11.5%, small incisional including trocar 21.3%. Preoperatively
      46.9% and 38.3% of patients reported symptomatic pain and movement scores,
      respectively. At 1 year, these were significantly reduced to 8.9% and 5.0%,
      respectively (p < 0.001). At 12 months hernia recurrence was 3.0% (95% CI, 1.2%
      to 6.1%), seroma (2.1%), infection (2.1%) with other events being less than 1%.
      These results indicate repair using this device led to significant improvement in
      pain and movement limitations and were associated with low complication and
      recurrence rates.

PMID- 24574020
TI  - Microbial fuel cells as discontinuous portable power sources: syntropic
      interactions with anode-respiring bacteria.
AB  - For microbial fuel cells (MFCs) to work as portable power sources used in a
      discontinuous manner, anode-respiring bacteria (ARB) should survive for at least
      several days in the absence of exogenous electron donors, and immediately
      generate current upon addition of an electron donor. Here, we proved that
      biopolymer-accumulating bacteria provide substrate (fuel) for ARB to generate
      current in lack of exogenous electron donor in 4 days, which allows MFCs to be
      used as portable power sources.

PMID- 24574021
TI  - Factors influencing total carbon dioxide concentrations in plasma of thoroughbred
      and standardbred racehorses.
AB  - Horse racing authorities impose a limit on the concentration of plasma 'total
      carbon dioxide' (TCO2), typically 36 mM with action taken above 37 mM, as
      measured by an electrochemical gas analyzer. It is of interest to understand the
      distribution of TCO2 in a 'normal' population of racehorses and determine
      probabilities of members of this population exceeding these current regulatory
      and action limits. TCO2 levels in equine plasma samples have been modelled for 12
      months (2011-2012) of thoroughbred (3076 measurements) and standardbred (3788
      measurements) data in Australia. The two populations have a common seasonal
      pattern, while the non-seasonal distributions differ. A single Gaussian
      distribution about the seasonal pattern explains the thoroughbred data, but there
      is evidence for a second Gaussian component for the standardbred horses. A
      Gaussian mixture model for standardbred horses gave a main component that matched
      the thoroughbred distribution, which was centred about 30.2 mM, and a smaller
      (about 20 % of the total density) Gaussian centred at 32.3 mM. The existence of a
      second, higher-meaned population of standardbred horses points to increased use
      of alkalinizing salts among a minority of trainers, whom still, however, maintain
      mostly legal levels of TCO2. Identification of this group can be used to direct
      intelligence-based testing with a view to limiting use of these products.
      Probabilities of exceeding limits are affected by seasonality, but the current
      rules remain conservative.

PMID- 24574023
TI  - The invisible wounds of war: caring for women veterans who have experienced
      military sexual trauma.
AB  - PURPOSE: The purpose of this case study is to raise awareness about military
      sexual trauma (MST) and posttraumatic stress disorder (PTSD), and the physical
      and psychological comorbidities associated with MST. DATA SOURCES: Health Science
      Data Sources-PubMed and authors' experiences. CONCLUSIONS: Women veterans are the
      fastest growing segment of the veteran population. Approximately 200,000 of the
      2.6 million veterans who have deployed in support of Operation Enduring
      Freedom/Operation Iraqi Freedom/Operation New Dawn (OEF/OIF/OND) are women. Many
      are seeking care in both the Veteran Administration and the civilian sector. It
      is estimated that upwards of 26,000 women have experienced some form of sexual
      assault in the military. MST can lead to multiple deleterious physical and
      psychological comorbidities. It is imperative that nurse practitioners (NPs) ask
      women about military service and utilize the Military Health History Pocket Card
      for Clinicians to ascertain service-connected health risks, primarily MST and
      PTSD. Prompt identification and intervention is key to reducing physical and
      psychological comorbidities. IMPLICATIONS FOR PRACTICE: This case study
      emphasizes the need for NPs to ask all women about military service and potential
      exposure to sexual trauma. It provides guidance on how to incorporate the
      Military Health History Pocket Card for Clinicians into practice.

PMID- 24574022
TI  - Diethylnitrosamine genotoxicity evaluated in sprague dawley rats using pig-a
      mutation and reticulocyte micronucleus assays.
AB  - Diethylnitrosamine (DEN) is a genotoxic carcinogen, but in vivo DNA-damaging
      activities are not usually evident in hematopoietic cells because the short-lived
      active metabolite is formed mainly in the liver. DEN therefore represented an
      interesting case for evaluating the performance characteristics of blood-based
      endpoints of genotoxicity that have been automated using flow cytometric analysis
      frequency of micronucleated reticulocytes and Pig-a mutant phenotype
      reticulocytes (RET(CD59-) ) and erythrocytes (RBC(CD59-) ). Male Sprague Dawley
      rats were treated for 28 consecutive days with DEN at levels up to 12.5
      mg/kg/day. Serial blood samples were collected and micronucleus frequencies were
      determined on Days 4 and 29, while RET(CD59-) and RBC(CD59-) frequencies were
      determined on Days 15, 29, and 42. The Pig-a analyses were conducted with an
      enrichment step based on immunomagnetic column separation to increase the
      statistical power of the assay. Modest but significant reductions to reticulocyte
      frequencies demonstrated that bone marrow was exposed to reactive intermediates.
      Even so, DEN did not affect micronucleus frequencies at any dose level tested.
      However, RET(CD59-) frequencies were significantly elevated in the high dose
      group on Day 29, and RBC(CD59-) were increased at this same dose level on Days 29
      and 42. These results demonstrate that the Pig-a assay is sufficiently sensitive
      to evaluate chemicals for genotoxic potential, even in the case of a promutagen
      that has traditionally required direct assessment(s) of liver tissue for
      detection of DNA-damage.

PMID- 24574024
TI  - Gene expression of TLR homologues identified by genome-wide screening of the
      earthworm Dendrobaena veneta.
AB  - TLRs represent one of the most important components of innate immunity.
      Currently, these receptors have been extensively studied in vertebrates and
      insects, but our knowledge for annelids is very limited. Therefore, the aim of
      our study was to identify earthworm TLR homologs by genome-wide screening, and to
      determine the expression of candidate genes as a response to Gram-positive and
      Gram-negative bacteria. Using a combination of deep pyrosequencing and
      quantitative PCR we found six candidate genes, for which all were expressed in
      Dentrobaena veneta. Two of the candidates showed significant response to
      bacterial exposure. In conclusion, TLRs seem to have a role in earthworm
      immunology. 

PMID- 24574025
TI  - Relationship between levels of neuropeptide Substance P in periodontal disease
      and chronic pain: a literature review.
AB  - The aim of the current review was to investigate the relationship between levels
      of neuropeptide Substance P in periodontal disease and chronic pain. Substance P
      is a neuropeptide that is directly related with pain. In periodontal disease, it
      is expressed during the inflammatory process, and is one of the factors
      responsible for bone resorption. Studies have shown that Substance P levels are
      highest in the gingival crevicular fluid from sites with active periodontal
      disease and bone loss. The persistence of these substances could be sufficient to
      stimulate neurogenic inflammation in susceptible tissues, and cause pain. The
      scientific literature shows that Substance P expressed during periodontal disease
      can be a risk factor for patients with systemic inflammatory pathologies, such as
      chronic arthritis or rheumatoid arthritis. Additional research is needed to
      confirm the participation of this substance in the origin of some types of
      chronic pain. 

PMID- 24574026
TI  - Structure-based engineering and comparison of novel split inteins for protein
      ligation.
AB  - Protein splicing is an autocatalytic process involving self-excision of an
      internal protein domain, the intein, and concomitant ligation of the two flanking
      sequences, the exteins, with a peptide bond. Protein splicing can also take place
      in trans by naturally split inteins or artificially split inteins, ligating the
      exteins on two different polypeptide chains into one polypeptide chain. Protein
      trans-splicing could work in foreign contexts by replacing the native extein
      sequences with other protein sequences. Protein ligation using protein trans
      splicing increasingly becomes a useful tool for biotechnological applications
      such as semi-synthesis of proteins, segmental isotopic labeling, and in vivo
      protein engineering. However, only a few split inteins have been successfully
      applied for protein ligation. Naturally split inteins have been widely used, but
      they are cross-reactive to each other, limiting their applications to multiple
      fragment ligation. Based on the three-dimensional structures including two newly
      determined intein structures, we derived 21 new split inteins from four highly
      efficient cis-splicing inteins, in order to develop novel split inteins suitable
      for protein ligation. We systematically compared trans-splicing of 24 split
      inteins and tested the cross-activities among them to identify orthogonal split
      intein fragments that could be used in chemical biology and biotechnological
      applications. 

PMID- 24574031
TI  - Fluoride-bridged {Gd(III)3M(III)2} (M = Cr, Fe, Ga) molecular magnetic
      refrigerants.
AB  - The reaction of fac-[M(III)F3(Me3tacn)]?x H2O with Gd(NO3)3?5H2O affords a series
      of fluoride-bridged, trigonal bipyramidal {Gd(III)3M(III)2} (M = Cr (1), Fe (2),
      Ga (3)) complexes without signs of concomitant GdF3 formation, thereby
      demonstrating the applicability even of labile fluoride-complexes as precursors
      for 3d-4f systems. Molecular geometry enforces weak exchange interactions, which
      is rationalized computationally. This, in conjunction with a lightweight ligand
      sphere, gives rise to large magnetic entropy changes of 38.3 J kg(-1)  K(-1) (1)
      and 33.1 J kg(-1)  K(-1) (2) for the field change 7 T->0 T. Interestingly, the
      entropy change, and the magnetocaloric effect, are smaller in 2 than in 1 despite
      the larger spin ground state of the former secured by intramolecular Fe-Gd
      ferromagnetic interactions. This observation underlines the necessity of
      controlling not only the ground state but also close-lying excited states for
      successful design of molecular refrigerants.

PMID- 24574032
TI  - Direct solvothermal synthesis of B/N-doped graphene.
AB  - Heteroatom-doping into graphitic networks has been utilized for opening the band
      gap of graphene. However, boron-doping into the graphitic framework is extremely
      limited, whereas nitrogen-doping is relatively feasible. Herein, boron/nitrogen
      co-doped graphene (BCN-graphene) is directly synthesized from the reaction of
      CCl4 , BBr3 , and N2 in the presence of potassium. The resultant BCN-graphene has
      boron and nitrogen contents of 2.38 and 2.66 atom %, respectively, and displays
      good dispersion stability in N-methyl-2-pyrrolidone, allowing for solution
      casting fabrication of a field-effect transistor. The device displays an on/off
      ratio of 10.7 with an optical band gap of 3.3 eV. Considering the scalability of
      the production method and the benefits of solution processability, BCN-graphene
      has high potential for many practical applications. 

PMID- 24574030
TI  - Chemically orthogonal three-patch microparticles.
AB  - Compared to two-dimensional substrates, only a few methodologies exist for the
      spatially controlled decoration of three-dimensional objects, such as
      microparticles. Combining electrohydrodynamic co-jetting with synthetic polymer
      chemistry, we were able to create two- and three-patch microparticles displaying
      chemically orthogonal anchor groups on three distinct surface patches of the same
      particle. This approach takes advantage of a combination of novel chemically
      orthogonal polylactide-based polymers and their processing by electrohydrodynamic
      co-jetting to yield unprecedented multifunctional microparticles. Several
      micropatterned particles were fabricated displaying orthogonal click
      functionalities. Specifically, we demonstrate novel two- and three-patch
      particles. Multi-patch particles are highly sought after for their potential to
      present multiple distinct ligands in a directional manner. This work clearly
      establishes a viable route towards orthogonal reaction strategies on multivalent
      micropatterned particles. 

PMID- 24574033
TI  - A high-pressure polymorph of phosphorus nitride imide.
AB  - Phosphorus nitride imide, PN(NH), is of great scientific importance because it is
      isosteric with silica (SiO2). Accordingly, a varied structural diversity could be
      expected. However, only one polymorph of PN(NH) has been reported thus far.
      Herein, we report on the synthesis and structural investigation of the first high
      pressure polymorph of phosphorus nitride imide, beta-PN(NH); the compound has
      been synthesized using the multianvil technique. By adding catalytic amounts of
      NH4Cl as a mineralizer, it became possible to grow single crystals of beta
      PN(NH), which allowed the first complete structural elucidation of a highly
      condensed phosphorus nitride from single-crystal X-ray diffraction data. The
      structure was confirmed by FTIR and (31)P and (1)H solid-state NMR spectroscopy.
      We are confident that high-pressure/high-temperature reactions could lead to new
      polymorphs of PN(NH) containing five-fold- or even six-fold-coordinated
      phosphorus atoms and thus rivalling or even surpassing the structural variety of
      SiO2.

PMID- 24574035
TI  - Graphenal polymers for energy storage.
AB  - A key to improve the electrochemical performance of energy storage systems (e.g.,
      lithium ion batteries and supercapacitors) is to develop advanced electrode
      materials. In the last few years, although originating from the unique structure
      and property of graphene, interest has expanded beyond the originally literally
      defined graphene into versatile integration of numerous intermediate structures
      lying between graphene and organic polymer, particularly for the development of
      new electrode materials for energy storage devices. Notably, diverse designations
      have shaded common characteristics of the molecular configurations of these newly
      emerging materials, severely impeding the design, synthesis, tailoring,
      functionalization, and control of functional electrode materials in a rational
      and systematical manner. This concept paper highlights all these intermediate
      materials, specifically comprising graphene subunits intrinsically interconnected
      by organic linkers or fractions, following a general concept of graphenal
      polymers. Combined with recent advances made by our group and others, two
      representative synthesis approaches (bottom-up and top-down) for graphenal
      polymers are outlined, as well as the structure-property relationships of these
      graphenal polymers as energy storage electrode materials are discussed. 

PMID- 24574034
TI  - Patient and therapist perspectives on alliance development: therapists' practice
      experiences as predictors.
AB  - Research has shown that the therapist's contribution to the alliance is more
      important for the outcome than the patient's contribution (e.g., Baldwin,
      Wampold, & Imel, 2007); however, knowledge is lacking about which therapist
      characteristics are relevant for alliance building and development. The objective
      of this study was to explore the development of the working alliance (using the
      Working Alliance Inventory), rated by both patients and therapists as a function
      of therapist in-session experiences. The therapist experiences were gathered by
      means of the Development of Psychotherapists Common Core Questionnaire (Orlinsky
      & Ronnestad, 2005). Data from the Norwegian Multisite Study of the Process and
      Outcome of Psychotherapy (Havik et al., 1995) were used. Multilevel growth curve
      analyses of alliance scores from Sessions 3, 12, 20 and 40 showed that the
      therapist factors predicted working alliance levels or growths differently,
      depending on whether the alliance was rated by patients or by therapists. For
      example, it emerged that therapists' negative reactions to patients and their in
      session anxiety affected patient-rated alliance but not therapist-rated alliance,
      whereas therapist experiences of flow (Csikszentmihalyi, 1990) during sessions
      impacted only the therapist-rated alliance. The patterns observed in this study
      imply that therapists should be particularly aware that their negative
      experiences of therapy are noticed by, and seem to influence, their clients when
      they evaluate the working alliance through the course of treatment. KEY
      PRACTITIONER MESSAGE: The findings of this study suggest that the working
      alliance is influenced by therapists' self-reported practice experiences, which
      presumably are communicated through the therapists' in-session behaviours. The
      study found a notable divergence between practice experiences that influenced the
      therapists and those that influenced the patients when evaluating the working
      alliance. Specifically, practitioners' self-reported difficulties in practice,
      such as their negative reactions to patients and their in-session anxiety,
      affected patient-rated alliance but not therapist-rated alliance, whereas
      therapist experiences of 'flow' during sessions impacted only the therapist-rated
      alliance. Practitioners should note that patient alliance ratings were more
      likely to be influenced by therapists' negative practice experiences than by
      positive ones. The divergence in the patient and therapist viewpoints has
      potential implications for therapist training and supervision and everyday self
      reflection.

PMID- 24574036
TI  - Fabrication of barium- and strontium-doped silica/titania hollow nanoparticles
      and their synergetic effects on promoting neuronal differentiation by activating
      ERK and p38 pathways.
AB  - Pristine, barium-doped, and strontium-doped hollow nanoparticles (p-HNPs, Ba-HNP,
      and Sr-HNP; HNPs) are prepared by sonication-mediated etching and redeposition
      (SMER) method and alkali-earth-metal hydroxide solution treatment. The HNPs are
      investigated to facilitate synergetic neuronal differentiation through alkali
      earth-metal doping and in conjunction with nerve growth factor (NGF). PC12 cells
      are used as model cells for neuronal differentiation. The differentiation
      efficiency is improved in the presence of the HNPs+NGF, and the neurite length is
      in the order of Sr-HNP+NGF > Ba-HNP+NGF > p-HNP+NGF > NGF. Silica/titania have
      increasing effect on both differentiation efficiency and neurite length, and
      doped barium/strontium influences additional elongation of the average neurite
      length. Take advantage of hollow structure, NGF is encapsulated into HNPs, and
      they are further applied for directly inducing differentiation. The maximum
      differentiation efficiency is 67% in presence of the NGF-encapsulated Sr-HNP,
      which was 1.3 times higher than previous research. Furthermore, the neurite
      length is also 2.7 times higher than MnO2 decorated poly(3,4
      ethylenedioxythiophene) nanoellipsoids. Ba- and Sr-HNP may offer a possibility
      for novel application of metal-hybrid nanomaterials for cell differentiation, and
      can be expanded to other cellular applications. 

PMID- 24574037
TI  - Thymol, a monoterpene phenolic derivative of cymene, abrogates mercury-induced
      oxidative stress resultant cytotoxicity and genotoxicity in hepatocarcinoma
      cells.
AB  - Thymol (TOH) was investigated for its ability to protect against mercuric
      chloride (HgCl2 )-induced cytotoxicity and genotoxicity using human
      hepatocarcinoma (HepG2) cell line. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl
      tetrazolium bromide assay confirmed the efficacy of TOH pretreatment in
      attenuating HgCl2 -induced cytotoxicity. Pretreatment with TOH inhibited HgCl2 
      induced genotoxicity, depolarization of mitochondrial membrane, oxidative stress,
      and mitochondrial superoxide levels. Interestingly, TOH (100 uM) alone elevated
      the intracellular basal glutathione S-transferase (GST) levels and TOH
      pretreatment abrogated the decrease in glutathione, GST, superoxide dismutase,
      and catalase levels even after HgCl2 intoxication. Furthermore, TOH was also
      capable of inhibiting HgCl2 -induced apoptotic as well as necrotic cell death
      analyzed by flowcytometric analysis of cells dual stained with Annexin
      FITC/propidium iodide. The present findings clearly indicate the cytoprotective
      potential of TOH against HgCl2 -induced toxicity, which may be attributed to its
      free radical scavenging ability which facilitated in reducing oxidative stress
      and mitochondrial damage thereby inhibiting cell death.

PMID- 24574038
TI  - Tracking CF disease progression with CT and respiratory symptoms in a cohort of
      children aged 6-19 years.
AB  - INTRODUCTION: Cystic fibrosis (CF) lung disease is characterized by
      bronchiectasis and trapped air on chest computed tomography (CT). OBJECTIVE: We
      aim to validate bronchiectasis and trapped air as outcome measures by evaluating
      associations between changes in bronchiectasis, trapped air and patient-reported
      respiratory symptoms. METHODS: A longitudinal cohort study has been conducted. CF
      patients (aged 6-19 years) who had two routine CTs and completed twice a Cystic
      Fibrosis Questionnaire-Revised within 2 years (referred to as T1 and T2 ), in the
      period of July 2007 to January 2012 were included. Bronchiectasis and trapped air
      were scored using the CF-CT scoring system. Correlation coefficients and
      student's paired t tests were performed. RESULTS: In total 40 patients were
      included with a median age at T1 of 12.6 years (range 6-17 years), and at T2 14.5
      years (range 8-19 years). At T1 , bronchiectasis (r = -0.49, P < 0.01) and
      trapped air (r = -0.34, P = 0.04) correlated with CFQ-R Respiratory Symptoms
      Scores (CFQ-R RSS). At T2 similar correlations were found with the CFQ-R RSS.
      Over 2 years, there was significant progression in bronchiectasis (P = 0.03) and
      trapped air (P = 0.03), but not in CFQ-R RSS. Changes in bronchiectasis and
      trapped air were not associated with changes in CFQ-R RSS. CONCLUSION: Our
      results indicate that bronchiectasis and trapped are sensitive outcome measures
      in CF lung disease, showing a significant association with CFQ-R RSS at two-time
      points. However, progression of bronchiectasis and trapped air over 2 year does
      not necessarily correlate to changes in quality of life.

PMID- 24574039
TI  - Cu2O/reduced graphene oxide composites for the photocatalytic conversion of CO2.
AB  - A facile one-step microwave-assisted chemical method has been successfully used
      for the synthesis of Cu2O/reduced graphene oxide (RGO) composites. Photocatalytic
      CO2 reduction was then investigated on the junction under ambient conditions. The
      RGO coating dramatically increases Cu2O activity for CO2 photoreduction to result
      in a nearly six times higher activity than the optimized Cu2O and 50 times higher
      activity than the Cu2O/RuOx junction in the 20(th) hour. Furthermore, an apparent
      initial quantum yield of approximately 0.34 % at 400 nm has been achieved by the
      Cu2O/RGO junction for CO2 photoreduction. The photocurrent of the junction is
      nearly double that of the blank Cu2O photocathode. The improved activity together
      with the enhanced stability of Cu2O is attributed to the efficient charge
      separation and transfer to RGO as well as the protection function of RGO, which
      was proved by XRD, SEM, TEM, X-ray photoelectron spectroscopy, photo
      electrochemical, photoluminescence, and impedance characterizations. This study
      further presents useful information for other photocatalyst modification for
      efficient CO2 reduction without the need for a noble-metal co-catalyst.

PMID- 24574040
TI  - Cavernomas of the human brainstem: 3-dimensional reconstruction from histological
      slides using computerized techniques.
AB  - Cerebral cavernous malformations (CCMs) are described as vascular lesions
      consisting of endothelial-lined dilated vessels embedded in a connective tissue
      sheath without intervening parenchyma between them. Their anatomical connections
      with the normal blood vessels are still enigmatic and the fine three-dimensional
      (3-D) organization of these vascular lesions remains to be established. Two
      stacks of serial histological slices, obtained from two brainstem CCM lesions
      (from the necropsy of a CCM2 male patient), were stained using Masson's trichrome
      method and then digitized. Stacks of regions of interest underwent quasi
      automatic processing: 1) propagative registering using blockmatching algorithms
      and Brain Visa programs; 2) 3-D segmentation using Aphelion; 3) display with
      Anatomist or ImageVis3D. These first histological 3-D reconstructions show the
      external limits of the caverns defined as the external limit of their collagen
      sheath. These pictures not only reveal the gross spatial organization of the
      lesions, but due to their high resolution (4 MUm) and with the help of simple
      anaglyphic 3-D rendering, they also allow the visualization of connections
      between caverns and very small blood vessels.

PMID- 24574041
TI  - Quantification of gamma- and alpha-tocopherol isomers in combination with pattern
      recognition model as a tool for differentiating dry-cured shoulders of Iberian
      pigs raised on different feeding systems.
AB  - BACKGROUND: Quantification of gamma- and alpha-tocopherol in dry-cured shoulders
      of Iberian pigs was evaluated as a tool for differentiating feeding backgrounds
      or regimens. Samples (n = 115) were obtained over two different seasons from the
      four categories of pigs described in the Industry Quality Policy, i.e. pigs fed
      in free-range conditions (FREE-RANGE), pigs fed in free-range conditions and
      provided feed supplements (FREE-FEED), pigs fed outdoors with feed and with
      access to grass (FEED-OUT) and pigs fed in intensive conditions with feed (FEED).
      Linear discriminant functions were calculated and validated. RESULTS: The
      validation results showed that 20% of the muscle samples were not correctly
      classified into the four feeding categories, giving an 80% success rate. The FEED
      group had the lowest proportion of errors, with 100% of samples correctly
      classified. For the FREE-RANGE group, 87% of samples were assigned to the correct
      feeding system by cross-validation; however, 13% were considered as FREE-FEED. A
      higher rate of correct classification can be obtained when using three categories
      or by calculating the weight gain in free-range conditions using regression
      equations. CONCLUSION: Taking into account the high variability of the samples
      and the high success in classification, these results are of interest and may be
      applied in practical situations.

PMID- 24574042
TI  - Growth and functional harvesting of human mesenchymal stromal cells cultured on a
      microcarrier-based system.
AB  - Human mesenchymal stromal cells (hMSCs) cells are attractive for applications in
      tissue engineering and cell therapy. Because of the low availability of hMSCs in
      tissues and the high doses of hMSCs necessary for infusion, scalable and cost
      effective technologies for in vitro cell expansion are needed to produce MSCs
      while maintaining their functional, immunophenotypic and cytogenetic
      characteristics. Microcarrier-based culture systems are a good alternative to
      traditional systems for hMSC expansion. The aim of the present study was to
      develop a scalable bioprocess for the expansion of human bone marrow mesenchymal
      stromal cells (hBM-MSCs) on microcarriers to optimize growth and functional
      harvesting. In general, the results obtained demonstrated the feasibility of
      expanding hBM-MSCs using microcarrier technology. The maximum cell concentration
      (n = 5) was ~4.82 +/- 1.18 * 10(5) cell mL(-1) at day 7, representing a 3.9-fold
      increase relative to the amount of inoculated cells. At the end of culture, 87.2%
      of the cells could be harvested (viability = 95%). Cell metabolism analysis
      revealed that there was no depletion of important nutrients such as glucose and
      glutamine during culture, and neither lactate nor ammonia byproducts were formed
      at inhibitory concentrations. The cells that were recovered after the expansion
      retained their immunophenotypic and functional characteristics. These results
      represent an important step toward the implementation of a GMP-compliant large
      scale production system for hMSCs for cellular therapy.

PMID- 24574043
TI  - Elevated S-adenosylhomocysteine alters adipocyte functionality with corresponding
      changes in gene expression and associated epigenetic marks.
AB  - Maternal deficiencies in micronutrients affecting one-carbon metabolism before
      and during pregnancy can influence metabolic status and the degree of insulin
      resistance and obesity of the progeny in adulthood. Notably, maternal and progeny
      plasma S-adenosylhomocysteine (SAH) levels are both elevated after vitamin
      deficiency in pregnancy. Therefore, we investigated whether this key one-carbon
      cycle intermediate directly affects adipocyte differentiation and function. We
      found that expansion and differentiation of murine 3T3-L1 preadipocytes in the
      presence of SAH impaired both basal and induced glucose uptake as well as
      lipolysis compared with untreated controls. SAH did not alter preadipocyte factor
      1 (Dlk1) or peroxisome proliferator-activated receptor-gamma 2 (Ppargamma2) but
      significantly reduced expression of CAAT enhancer-binding protein-alpha
      (Cebpalpha), Cebpbeta, and retinoid x receptor-alpha (Rxralpha) compared with
      untreated adipocytes. SAH increased Rxralpha methylation on a CpG unit
      (chr2:27,521,057+, chr2:27,521,049+) and CpG residue (chr2:27,521,080+), but not
      Cebpbeta methylation, relative to untreated adipocytes. Trimethylated histone H3
      Lys27 occupancy was significantly increased on Cebpalpha and Rxralpha promoters
      in SAH-treated adipocytes, consistent with the reduction in gene expression. In
      conclusion, SAH did not affect adipogenesis per se but altered adipocyte
      functionality through epigenetic mechanisms, such that they exhibited altered
      glucose disposal and lipolysis. Our findings implicate micronutrient imbalance in
      subsequent modulation of adipocyte function. 

PMID- 24574045
TI  - Early detection of nerve fiber loss by corneal confocal microscopy and skin
      biopsy in recently diagnosed type 2 diabetes.
AB  - We sought to determine whether early nerve damage may be detected by corneal
      confocal microscopy (CCM), skin biopsy, and neurophysiological tests in 86
      recently diagnosed type 2 diabetic patients compared with 48 control subjects.
      CCM analysis using novel algorithms to reconstruct nerve fiber images was
      performed for all fibers and major nerve fibers (MNF) only. Intraepidermal nerve
      fiber density (IENFD) was assessed in skin specimens. Neurophysiological measures
      included nerve conduction studies (NCS), quantitative sensory testing (QST), and
      cardiovascular autonomic function tests (AFTs). Compared with control subjects,
      diabetic patients exhibited significantly reduced corneal nerve fiber length
      (CNFL-MNF), fiber density (CNFD-MNF), branch density (CNBD-MNF), connecting
      points (CNCP), IENFD, NCS, QST, and AFTs. CNFD-MNF and IENFD were reduced below
      the 2.5th percentile in 21% and 14% of the diabetic patients, respectively.
      However, the vast majority of patients with abnormal CNFD showed concomitantly
      normal IENFD and vice versa. In conclusion, CCM and skin biopsy both detect nerve
      fiber loss in recently diagnosed type 2 diabetes, but largely in different
      patients, suggesting a patchy manifestation pattern of small fiber neuropathy.
      Concomitant NCS impairment points to an early parallel involvement of small and
      large fibers, but the precise temporal sequence should be clarified in
      prospective studies. 

PMID- 24574046
TI  - Postpartum depression in immigrant Hispanic women: a comparative community
      sample.
AB  - PURPOSE: To determine whether a high rate of postpartum depression (PPD),
      previously found in immigrant Hispanic women at a community clinic, would also be
      found in a community sample. DATA SOURCES: Sixty women from local community
      settings were given the PPDS-S instrument and the General Acculturation Index to
      screen for PPD symptoms. Data were then compared with previously published
      community clinic data. CONCLUSION: Sixty percent of the immigrant Hispanic women
      showed significant PPD. The only statistically significant positive predictive
      factor for increased PPD symptoms was having a previous history of depression. In
      addition, 54% had an elevated symptom content profile score for suicidal
      thinking. IMPLICATIONS FOR PRACTICE: Health practitioners should be aware of a
      potentially high rate of PPD in this population, especially in light of
      previously studied increased rates of suicide attempts in Latinas. If a prior
      history of depression is predictive of PPD, it is possible that many of the
      mothers in our sample suffered from depression prior to the postpartum period,
      but were not appropriately diagnosed or treated. Recommendations for outreach and
      further research are discussed. In particular, further research regarding the
      prenatal prevalence of depression in immigrant Hispanic women is recommended in
      order to further understand the high incidence of PPD.

PMID- 24574044
TI  - Linagliptin-mediated DPP-4 inhibition ameliorates kidney fibrosis in
      streptozotocin-induced diabetic mice by inhibiting endothelial-to-mesenchymal
      transition in a therapeutic regimen.
AB  - Kidney fibrosis is the final common pathway of all progressive chronic kidney
      diseases, of which diabetic nephropathy is the leading cause. Endothelial-to
      mesenchymal transition (EndMT) has emerged as one of the most important origins
      of matrix-producing fibroblasts. Dipeptidyl peptidase-4 (DPP-4) inhibitors have
      been introduced into the market as antidiabetes drugs. Here, we found that the
      DPP-4 inhibitor linagliptin ameliorated kidney fibrosis in diabetic mice without
      altering the blood glucose levels associated with the inhibition of EndMT and the
      restoration of microRNA 29s. Streptozotocin-induced diabetic CD-1 mice exhibited
      kidney fibrosis and strong immunoreactivity for DPP-4 by 24 weeks after the onset
      of diabetes. At 20 weeks after the onset of diabetes, mice were treated with
      linagliptin for 4 weeks. Linagliptin-treated diabetic mice exhibited a
      suppression of DPP-4 activity/protein expression and an amelioration of kidney
      fibrosis associated with the inhibition of EndMT. The therapeutic effects of
      linagliptin on diabetic kidneys were associated with the suppression of
      profibrotic programs, as assessed by mRNA microarray analysis. We found that the
      induction of DPP-4 observed in diabetic kidneys may be associated with suppressed
      levels of microRNA 29s in diabetic mice; linagliptin restored microRNA 29s and
      suppressed DPP-4 protein levels. Using cultured endothelial cells, we found that
      linagliptin inhibited TGF-beta2-induced EndMT, and such anti-EndMT effects of
      linagliptin were mediated through microRNA 29 induction. These results indicate
      the possible novel pleiotropic action of linagliptin to restore normal kidney
      function in diabetic patients with renal impairment.

PMID- 24574047
TI  - The delayed-release combination of doxylamine and pyridoxine
      (Diclegis(r)/Diclectin (r)) for the treatment of nausea and vomiting of
      pregnancy.
AB  - Nausea and vomiting of pregnancy (NVP) affects up to 85 % of all pregnancies.
      Effective treatment can greatly improve a woman's quality of life, reduce the
      risk for maternal and fetal complications, and reduce healthcare costs.
      Unfortunately, many women receive either no pharmacological treatment or are
      recommended therapies for which fetal safety and efficacy have not been
      established. First-line treatment of NVP, as recommended by several leading
      healthcare and professional organizations, is the combination of doxylamine and
      pyridoxine. This combination, formulated as a 10 mg/10 mg delayed-release tablet,
      was approved by the US Food and Drug Administration (FDA) for the treatment of
      NVP in April 2013 under the brand name Diclegis((r)), and has been on the
      Canadian market since 1979, currently under the brand name Diclectin((r)). The
      efficacy of Diclegis((r))/Diclectin((r)) has been demonstrated in several
      clinical trials, and, more importantly, studies on more than 200,000 women
      exposed to doxylamine and pyridoxine in the first trimester of pregnancy have
      demonstrated no increased fetal risk for congenital malformations and other
      adverse pregnancy outcomes. The present review aims to present the scientific
      evidence on the effectiveness and fetal safety of Diclegis((r))/Diclectin((r))
      for the treatment of NVP to justify its use as first-line treatment for NVP.

PMID- 24574049
TI  - Activation of ErbB2- ErbB3 signaling pathway supports potential therapeutic
      activity of ErbB inhibitors in AT/RT.

PMID- 24574048
TI  - Cerulenin inhibits unsaturated fatty acids synthesis in Bacillus subtilis by
      modifying the input signal of DesK thermosensor.
AB  - Bacillus subtilis responds to a sudden decrease in temperature by transiently
      inducing the expression of the des gene encoding for a lipid desaturase, Delta5
      Des, which introduces a double bond into the acyl chain of preexisting membrane
      phospholipids. This Delta5-Des-mediated membrane remodeling is controlled by the
      cold-sensor DesK. After cooling, DesK activates the response regulator DesR,
      which induces transcription of des. We show that inhibition of fatty acid
      synthesis by the addition of cerulenin, a potent and specific inhibitor of the
      type II fatty acid synthase, results in increased levels of short-chain fatty
      acids (FA) in membrane phospholipids that lead to inhibition of the transmembrane
      input thermal control of DesK. Furthermore, reduction of phospholipid synthesis
      by conditional inactivation of the PlsC acyltransferase causes significantly
      elevated incorporation of long-chain FA and constitutive upregulation of the des
      gene. Thus, we provide in vivo evidence that the thickness of the hydrophobic
      core of the lipid bilayer serves as one of the stimulus sensed by the membrane
      spanning region of DesK.

PMID- 24574050
TI  - Diffusion abnormalities of the corpus callosum in patients receiving bevacizumab
      for malignant brain tumors: suspected treatment toxicity.
AB  - Bevacizumab has been reported to cause diffusion restriction in the tumor bed of
      patients with malignant gliomas. This study evaluated prolonged diffusion
      restriction, in the corpus callosum (CC), of patients with malignant brain tumors
      treated with bevacizumab. We retrospectively reviewed our database of patients
      treated with bevacizumab for malignant brain tumors looking for those with
      restricted diffusion in the CC. CC ADC ratio measurements were obtained prior to
      and following treatment. Correlation was made with biopsy (n = 3) and MR
      perfusion (n = 7) and PET (n = 4). The temporal evolution of these changes
      relative to therapy was examined with mixed effects regression analysis. Nine
      patients (eight malignant gliomas, one malignant meningioma) out of 146 patients
      were found to have developed areas of diffusion restriction in the CC. These
      areas tended to enlarge and coalesce over serial MRIs and persisted for up to 22
      months. Hypoperfusion was demonstrated in MR perfusion in 7/7. PET was
      hypometabolic in all 4. Biopsy of the CC showed no tumor in 3/3. ADC ratio
      measurements indicated a significant overall effect of time (F(16,60) = 11.2; p <
      0.0001), consistent with persistent diffusion restriction over the measured time
      periods. Bevacizumab causes prolonged diffusion restriction in the CC. The
      negative MR perfusion, FDG PET and histopathology suggest this is a toxicity of
      bevacizumab and not active tumor. Awareness of these changes can assist in
      patient care. 

PMID- 24574053
TI  - Electrochemistry of nanoparticles.
AB  - Metal nanoparticles (NPs) find widespread application as a result of their unique
      physical and chemical properties. NPs have generated considerable interest in
      catalysis and electrocatalysis, where they provide a high surface area to mass
      ratio and can be tailored to promote particular reaction pathways. The activity
      of NPs can be analyzed especially well using electrochemistry, which probes
      interfacial chemistry directly. In this Review, we discuss key issues related to
      the electrochemistry of NPs. We highlight model studies that demonstrate
      exceptional control over the NP shape and size, or mass-transport conditions,
      which can provide key insights into the behavior of ensembles of NPs. Particular
      focus is on the challenge of ultimately measuring reactions at individual NPs,
      and relating the response to their structure, which is leading to imaginative
      experiments that have an impact on electrochemistry in general as well as broader
      surface and colloid science. 

PMID- 24574052
TI  - Clinical and microbiological effects of levofloxacin in the treatment of chronic
      periodontitis: a randomized, placebo-controlled clinical trial.
AB  - AIM: The aim of the present study was to evaluate the clinical and
      microbiological effect of systemic levofloxacin (LFX) as an adjunct to scaling
      and root planing (SRP) in patients with chronic periodontitis (CP). METHODS:
      Sixty-five patients with CP were randomly divided into a test (n = 33, SRP and
      LFX 500 mg, once daily [o.d.]) and a control group (n = 32, SRP and placebo,
      o.d.). Plaque index (PI), gingival index (GI), percentage of sites with bleeding
      on probing (%BoP), probing depth (PD), and clinical attachment level (CAL) were
      recorded at baseline, 10 days, and 1-, 3-, and 6-month intervals. The percentage
      of sites positive for Aggregatibacter actinomycetemcomitans (A.
      actinomycetemcomitans), Porphyromonas gingivalis, and Tannerella forsythia were
      recorded at baseline and at 3 and 6 months. RESULTS: Patients receiving LFX
      showed statistically-significant improvements in mean PD and CAL. The intergroup
      difference in PI, GI, and%BoP was not significant at any interval. There was a
      reduction in the percentage of sites positive for periodontopathic bacteria over
      the duration of the study in both groups, and a statistically-significant
      reduction in the number of sites positive for A. actinomycetemcomitans in the LFX
      group (P < 0.001). CONCLUSION: Levofloxacin was found to significantly improve
      the clinical and microbiological parameters in CP individuals.

PMID- 24574051
TI  - Phosphorylation of alpha-tubulin by protein kinase C stimulates microtubule
      dynamics in human breast cells.
AB  - Protein kinase C (PKC) engenders motility through phosphorylation of alpha
      tubulin at Ser-165 in nontransformed MCF-10A cells. Live cell imaging explored
      the impact of PKC-mediated phosphorylation on microtubule (MT) dynamics. MTs
      fluorescently labeled with GFP-alpha-tubulin were treated with diacylglycerol
      (DAG)-lactone (a membrane-permeable PKC activator), or cotransfected with a
      pseudophosphorylated S165D-alpha6-tubulin mutant. Each condition increased the
      dynamicity of MTs by stimulating the rate and duration of the growth phase and
      decreasing the frequency of catastrophe. In MDA-MB-231 metastatic breast cells
      where the intrinsic PKC activity is high, these MT growth parameters were also
      high but could be suppressed by expression of phosphorylation-resistant S165N
      alpha6-tubulin or by treatment with a pan-PKC inhibitor (bis-indoleylmaleimide).
      Subcellular fractionation and immunofluorescence of MCF-10A cells showed that
      phosphorylation (via DAG-lactone) or pseudophosphorylation of alpha6-tubulin
      increased its partitioning into MTs as compared to controls, and produced longer,
      more stable MTs. Following expression of the plus-end binding protein GFP-EB1,
      DAG-lactone accelerated the formation and increased the number of nascent MTs.
      Expression of S165D-alpha6-tubulin promoted Rac1 activation and Rac1-dependent
      cell motility. These findings call attention to PKC-mediated phosphorylation of
      alpha-tubulin as a novel mechanism for controlling the dynamics of MTs that
      result in cell movement.

PMID- 24574055
TI  - Neck circumference percentile: A screening tool for pediatric obstructive sleep
      apnea.
AB  - RATIONALE: Large neck circumference (NC) is associated with obstructive sleep
      apnea (OSA) in adults, especially males. Since NC changes with age and sex, a
      lack of reference ranges makes neck size difficult to assess as a screening tool
      in children. METHODS: Using a population-based dataset of 1,913 children, we
      developed reference ranges for NC by age and sex for children aged 6-17 years. In
      this study, we collected NC data on 245 children aged 6-17 years presenting to
      the Children's Hospital of Eastern Ontario for polysomnography. The association
      between NC>the 95th percentile and OSA (total apnea-hypopnea-index>5 events/hr
      and/or obstructive-apnea-index >= 1 event/hr) was explored. Thresholds of BMI
      percentile and waist circumference were also examined. RESULTS: Individuals with
      NC>95th percentile for age and sex had increased risk of OSA (relative risk 1.7
      [95% CI 1.0-3.0], P=0.04), compared to those with NC <= 95th percentile. BMI >=
      95th percentile gave similar results (relative risk 1.8 [95% CI 1.1-2.9],
      P=0.02). When examined by sex, the association was significant in males >= 12
      years (relative risk 3.3 [95% CI 1.0-10.4], P=0.04), but not females (P=0.63).
      Neither BMI  >= 95th percentile nor waist circumference>95th percentile was
      significant. CONCLUSIONS: Children and youth with NC>95th percentile for age and
      sex have significantly increased risk of OSA. This effect is significant in males
      >= 12 years, whereas BMI is not. NC percentile may be an additional screening
      tool for OSA in children and youth.

PMID- 24574056
TI  - Electric fields in unsteady wind-blown sand.
AB  - The electrification of wind-blown sand has been widely confirmed by field and
      wind-tunnel measurements. It plays an important role in the lifting and transport
      of sand particles. In this study we investigated the behavior of electric fields
      in unsteady saltation by adopting periodic variation wind sequences. The
      influence of electric fields on sand transport rate was also discussed. The
      results show that both horizontal and vertical electric fields exist in unsteady
      saltation, and the transport rate in unsteady saltation is less than that in
      steady saltation. An interesting result is that the directions of vertical
      electric field fluctuate upward and downward-pointing with time in the unsteady
      saltation. This provides a possible explanation for the bipolar pattern of the
      vertical electric field in wind-blown sand. 

PMID- 24574054
TI  - Three-dimensional paper-based model for cardiac ischemia.
AB  - In vitro models of ischemia have not historically recapitulated the cellular
      interactions and gradients of molecules that occur in a 3D tissue. This work
      demonstrates a paper-based 3D culture system that mimics some of the interactions
      that occur among populations of cells in the heart during ischemia. Multiple
      layers of paper containing cells, suspended in hydrogels, are stacked to form a
      layered 3D model of a tissue. Mass transport of oxygen and glucose into this 3D
      system can be modulated to induce an ischemic environment in the bottom layers of
      the stack. This ischemic stress induces cardiomyocytes at the bottom of the stack
      to secrete chemokines which subsequently trigger fibroblasts residing in adjacent
      layers to migrate toward the ischemic region. This work demonstrates the
      usefulness of patterned, stacked paper for performing in vitro mechanistic
      studies of cellular motility and viability within a model of the laminar
      ventricle tissue of the heart. 

PMID- 24574057
TI  - Hyperbranched polymer stars with Gaussian chain statistics revisited.
AB  - Conformational properties of regular dendrimers and more general hyperbranched
      polymer stars with Gaussian statistics for the spacer chains between branching
      points are revisited numerically. We investigate the scaling for asymptotically
      long chains especially for fractal dimensions df = 3 (marginally compact) and df
      = 2.5 (diffusion limited aggregation). Power-law stars obtained by imposing the
      number of additional arms per generation are compared to truly self-similar
      stars. We discuss effects of weak excluded-volume interactions and sketch the
      regime where the Gaussian approximation should hold in dense solutions and melts
      for sufficiently large spacer chains.

PMID- 24574059
TI  - Is individualized medicine more cost-effective? A systematic review.
AB  - BACKGROUND: Individualized medicine (IM) is a rapidly evolving field that is
      associated with both visions of more effective care at lower costs and fears of
      highly priced, low-value interventions. It is unclear which view is supported by
      the current evidence. OBJECTIVE: Our objective was to systematically review the
      health economic evidence related to IM and to derive general statements on its
      cost-effectiveness. DATA SOURCES: A literature search of MEDLINE database for
      English- and German-language studies was conducted. STUDY APPRAISAL AND SYNTHESIS
      METHOD: Cost-effectiveness and cost-utility studies for technologies meeting the
      MEDLINE medical subject headings (MeSH) definition of IM (genetically targeted
      interventions) were reviewed. This was followed by a standardized extraction of
      general study characteristics and cost-effectiveness results. RESULTS: Most of
      the 84 studies included in the synthesis were from the USA (n = 43, 51 %), cost
      utility studies (n = 66, 79 %), and published since 2005 (n = 60, 71 %). The
      results ranged from dominant to dominated. The median value (cost-utility
      studies) was calculated to be rounded $US22,000 per quality-adjusted life year
      (QALY) gained (adjusted to $US, year 2008 values), which is equal to the rounded
      median cost-effectiveness in the peer-reviewed English-language literature
      according to a recent review. Many studies reported more than one strategy of IM
      with highly varying cost-effectiveness ratios. Generally, results differed
      according to test type, and tests for disease prognosis or screening appeared to
      be more favorable than tests to stratify patients by response or by risk of
      adverse effects. However, these results were not significant. LIMITATIONS:
      Different definitions of IM could have been used. Quality assessment of the
      studies was restricted to analyzing transparency. CONCLUSIONS: IM neither seems
      to display superior cost-effectiveness than other types of medical interventions
      nor to be economically inferior. Instead, rather than 'whether' healthcare was
      individualized, the question of 'how' it was individualized was of economic
      relevance.

PMID- 24574058
TI  - N-glycomic profiling of a glucosidase II mutant of Dictyostelium discoideum by
      ''off-line'' liquid chromatography and mass spectrometry.
AB  - In this study, we have performed the first mass spectrometric analysis of N
      glycans of the M31 mutant strain of the cellular slime mould Dictyostelium
      discoideum, previously shown to have a defect in glucosidase II. Together with
      glucosidase I, this enzyme mediates part of the initial processing of N-glycans;
      defects in either glucosidase are associated with human diseases and result in an
      accumulation of incorrectly processed oligosaccharides which are not, or only
      poor, substrates for a range of downstream enzymes. To examine the effect of the
      glucosidase II mutation in Dictyostelium, we employed off-line LC-MALDI-TOF MS in
      combination with chemical and enzymatic treatments and MS/MS to analyze the
      neutral and anionic N-glycans of the mutant as compared to the wild type. The
      major neutral species were, as expected, of the composition Hex10-11 HexNAc2-3
      with one or two terminal glucose residues. Consistent with the block in
      processing of neutral N-glycans caused by the absence of glucosidase II, fucose
      was apparently absent from the N-glycans and bisecting N-acetylglucosamine was
      rare. The major anionic oligosaccharides were sulfated and/or
      methylphosphorylated forms of Hex8-11 HexNAc2-3 , many of which surprisingly
      lacked glucose residues entirely. As anionic N-glycans are considered to be
      mostly associated with lysosomal enzymes in Dictyostelium, we hypothesise that
      glycosidases present in the acidic compartments may act on the oligosaccharides
      attached to such slime mould proteins. Furthermore, our chosen analytical
      approach enabled us, via observation of diagnostic negative-mode MS/MS fragments,
      to determine the fine structure of the methylphosphorylated and sulfated N
      glycans of the M31 glucosidase mutant in their native state. 

PMID- 24574061
TI  - Light therapy for improving cognition, activities of daily living, sleep,
      challenging behaviour, and psychiatric disturbances in dementia.
AB  - BACKGROUND: Rest-activity and sleep-wake cycles are controlled by the endogenous
      circadian rhythm generated by the suprachiasmatic nuclei (SCN) of the
      hypothalamus. Degenerative changes in the SCN appear to be a biological basis for
      circadian disturbances in people with dementia, and might be reversed by
      stimulation of the SCN by light. OBJECTIVES: The review examines the
      effectiveness of light therapy in improving cognition, activities of daily living
      (ADLs), sleep, challenging behaviour, and psychiatric symptoms associated with
      dementia. SEARCH METHODS: ALOIS, the Specialized Register of the Cochrane
      Dementia and Cognitive Improvement Group (CDCIG), The Cochrane Library, MEDLINE,
      EMBASE, PsycINFO, CINAHL and LILACS were searched on 20 January 2014 using the
      terms: "bright light*", "light box*", "light visor*", "dawn-dusk*", phototherapy,
      "photo therapy", "light therapy" "light treatment", light* . The CDCIG
      Specialized Register contains records from all major healthcare databases (The
      Cochrane Library, MEDLINE, EMBASE, PsycINFO, CINAHL, LILACS) as well as from many
      trials databases and grey literature sources. SELECTION CRITERIA: All relevant,
      randomized controlled trials were included in which light therapy, at any
      intensity and duration, was compared with a control group for the effect of
      improving cognition, ADLs, sleep, challenging behaviour, and psychiatric symptoms
      associated with dementia (as well as institutionalization rates or cost of care).
      Included were people with dementia of any type and degree of severity. DATA
      COLLECTION AND ANALYSIS: Two review authors independently assessed the retrieved
      articles for relevance, and four review authors independently assessed the
      selected studies for risk of bias and extracted the data. Statistically
      significant differences in outcomes between the treatment and control groups at
      the end of treatment and follow-up were examined. Each study was summarized using
      a measure of effect (for example mean difference). MAIN RESULTS: Eleven trials
      (13 articles) met the inclusion criteria. However, three of the studies could not
      be included in the analyses either because the reported data could not be used in
      the meta-analysis or we were unable to retrieve the required data from the
      authors.This updated review found no effect of light therapy on cognitive
      function, sleep, challenging behaviour (for example agitation), or psychiatric
      symptoms associated with dementia. Reduction in the development of ADL
      limitations was reported in one study, at three of five time points, and light
      therapy was found to have an effect after six weeks and two years but not after
      one year. AUTHORS' CONCLUSIONS: There is insufficient evidence to justify the use
      of bright light therapy in dementia. Further research should concentrate on
      replicating the suggested effect on ADLs, and establishing the biological
      mechanism for how light therapy improves these important outcomes.

PMID- 24574062
TI  - Nickel-tungsten carbide catalysts for the production of 2,5-dimethylfuran from
      biomass-derived molecules.
AB  - The development of new catalytic systems for the conversion of biomass-derived
      molecules into liquid fuels has attracted much attention. We propose a non-noble
      bimetallic catalyst based on nickel-tungsten carbide for the conversion of the
      platform molecules 5-(hydroxymethyl)furfural into the liquid-fuel molecule 2,5
      dimethylfuran (DMF). Different catalysts, metal ratios and reaction conditions
      have been tested and give rise to a 96% yield of DMF. The catalysts have been
      characterized and are discussed. The reaction mechanism is also explored through
      capture of reaction intermediates. The analysis of the reaction mixture over
      different catalysts is presented and helps to understand the role of nickel and
      tungsten carbide during the reaction.

PMID- 24574060
TI  - Prospective evaluation of potential toxicity of repeated doses of Thymus vulgaris
      L. extracts in rats by means of clinical chemistry, histopathology and NMR-based
      metabonomic approach.
AB  - In the field of natural extracts, research generally focuses on the study of
      their biological activities for food, cosmetic, or pharmacological purposes. The
      evaluation of their adverse effects is often overlooked. In this study, the
      extracts of Thymus vulgaris L. were obtained by two different extraction methods.
      Intraperitoneal injections of both extracts were given daily for four days to
      male Wistar Han rats, at two different doses for each extract. The evaluation of
      the potential toxic effects included histopathological examination of liver,
      kidney, and lung tissues, as well as serum biochemistry of liver and kidney
      parameters, and (1)H-NMR-based metabonomic profiles of urine. The results showed
      that no histopathological changes were observed in the liver and kidney in rats
      treated with both extracts of thyme. Serum biochemical investigations revealed
      significant increases in blood urea nitrogen, creatinine, and uric acid in
      animals treated with polyphenolic extract at both doses. In these latter groups,
      metabonomic analysis revealed alterations in a number of urine metabolites
      involved in the energy metabolism in liver mitochondria. Indeed, the results
      showed alterations of glycolysis, Krebs cycle, and beta-oxidative pathways as
      evidenced by increases in lactate and ketone bodies, and decreases in citrate,
      alpha-ketoglutarate, creatinine, hippurate, dimethylglycine, and dimethyalanine.
      In conclusion, this work showed that i.p. injection of repeated doses of thyme
      extracts causes some disturbances of intermediary metabolism in rats. The
      metabonomic study revealed interesting data which could be further used to
      determine the cellular pathways affected by such treatments.

PMID- 24574063
TI  - Mission accomplished: over and out.

PMID- 24574064
TI  - Exploring the pragmatic and explanatory study design on outcomes of systematic
      reviews of public health interventions: a case study on obesity prevention
      trials.

PMID- 24574066
TI  - Lack of synergistic interaction between the two mechanisms of action of
      tapentadol in gastrointestinal transit.
AB  - BACKGROUND: A multi-mechanistic approach offers potential enhancement of
      analgesic efficacy, but therapeutic gain could be offset by an increase in
      adverse events. The centrally acting analgesic tapentadol [(-)-(1R,2R)-3-(3
      dimethylamino-1-ethyl-2-methyl-propyl)-phenol hydrochloride] combines MU-opioid
      receptor (MOR) agonism and neuronal noradrenaline reuptake inhibition (NRI), both
      of which contribute to its analgesic effects. Previously, isobolographic analysis
      of occupation-effect data and a theoretically equivalent methodology determining
      interactions from the effect scale demonstrated pronounced synergistic
      interaction between the two mechanisms of action of tapentadol in two models of
      antinociception (low-intensity tail-flick and spinal nerve ligation). The present
      study investigated the nature of interaction of the two mechanisms on a surrogate
      measure for gastrointestinal adverse effect (inhibition of gastrointestinal
      transit). METHODS: Dose-response curves were generated in rats for tapentadol
      alone or in combination with the opioid receptor antagonist, naloxone, or the
      alpha2 -adrenoceptor antagonist, yohimbine, to reveal the effect of tapentadol
      based upon MOR agonism, NRI, and combined mechanisms. RESULTS: The dose-effect
      curve of tapentadol was shifted to the right by both antagonists, thereby
      providing data to distinguish between MOR agonism and NRI. Analysis revealed a
      simple additive interaction between the two mechanisms on this endpoint, in
      contrast to the synergistic interaction previously demonstrated for
      antinociception. CONCLUSIONS: We believe this is the first published evaluation
      of mechanistic interaction for a surrogate measure of adverse effect of a single
      compound with two mechanisms of action, and the results suggest that there is a
      greater separation between the analgesic and gastrointestinal effects of
      tapentadol than expected based upon its analgesic efficacy.

PMID- 24574067
TI  - Gene regulatory networks and epigenetic modifications in cell differentiation.
AB  - It is becoming increasingly clear that the functionalities of an organism are
      mostly derived from regulation of its gene repertoire. Specialized cell types are
      created from pluripotent stem cells by regulating expression of genes. In
      eukaryotes, genes are primarily regulated by gene regulatory networks consisting
      of highly sequence-specific transcription factors and epigenetic modifications.
      The former mode of regulation is more readily reversible and non-heritable across
      cell generations, whereas the latter mode is less reversible and heritable. In
      this article, we explore the relationship between cell differentiation and the
      two modes of regulation of gene expression, focusing primarily on pluripotent and
      multipotent stem cells. Recent studies suggest that stem cells execute different
      gene expression programs, probably driven by one or more gene regulatory
      network(s). It is now also evident that as stem cells differentiate to more
      specialized progeny cells, rewriting of epigenetic marks occurs in parallel with
      the change in the pattern of gene expression. A conceptual framework is put
      forward in which it is proposed that the cell fate determining gene regulatory
      network in a pluripotent or multipotent cell has the capability to exist in
      multiple stationary states with each stationary state dictating a particular
      pattern of gene expression. We also propose that the broad pattern of gene
      expression in each stationary state, termed the lineage biased state or LIBS,
      resembles that of a more differentiated progeny cell. The differentiation process
      leading to a particular progeny cell involves rewriting of epigenetic marks that
      result in upregulation of genes in a LIBS and silencing of genes involved in
      alternative LIBS; thus selecting a particular pattern of gene expression and
      making a lineage commitment.

PMID- 24574065
TI  - Complexity in regulation of microRNA machinery components in invasive breast
      carcinoma.
AB  - Altered expression of microRNA (miRNA) machinery components may play an important
      role in breast cancer progression. The objective of the current study was to
      evaluate Drosha, the DiGeorge syndrome critical region gene 8 (DGCR8), Dicer, and
      Argonaute 2 (AGO2) mRNA expression in invasive breast carcinoma (IBC) and to
      assess the value of clinical parameters on their expression. By using
      quantitative real-time PCR, we examined the expression of the four miRNA
      machinery components in 52 breast tumor tissues which are diagnosed as invasive
      ductal carcinoma and adjacent non-neoplastic tissues. In the present study,
      decreased mRNA expression levels of major miRNA machinery components were
      observed in IBC. The altered mRNA expression levels of DGCR8 and AGO2 are
      positively correlated with to each other. This study revealed for the first time
      that expression alterations of DGCR8 are significantly associated with estrogen
      receptor and Ki-67 status in IBC. Moreover, AGO2 mRNA expression level was
      significantly correlated with N stage. These results provided evidences that down
      regulated the four miRNA machinery components may play an important role in
      breast pathobiology and that DGCR8 and AGO2 might be associated with important
      clinical factors. 

PMID- 24574068
TI  - Viscosupplementation for knee osteoarthritis.
AB  - PURPOSE: To provide an overview of the diagnosis and pathophysiology of
      osteoarthritis (OA), and to describe appropriate treatments for knee OA, with a
      focus on the efficacy and safety of viscosupplementation. Because nurse
      practitioners (NPs) can inject viscosupplements, a section on injection technique
      is included. DATA SOURCES: Manuscripts were identified using PubMed and EMBASE
      with a review of the reference lists from retrieved articles. CONCLUSIONS:
      Viscosupplements are safe and effective at improving function and alleviating
      knee pain from OA for up to 26 weeks. IMPLICATIONS FOR PRACTICE: As the number of
      patients with OA is increasing, NPs need to be prepared to prescribe various
      treatment options to alleviate osteoarthritic knee pain, including
      viscosupplementation.

PMID- 24574069
TI  - Isolation of viable but nonculturable Vibrio cholerae O1 from environmental water
      samples in Kolkata, India, in a culturable state.
AB  - Previously, we reported that viable but nonculturable (VBNC) Vibrio cholerae was
      converted into a culturable state by coculture with several eukaryotic cell lines
      including HT-29 cells. In this study, we found that a factor converting VBNC V.
      cholerae into a culturable state (FCVC) existed in cell extracts of eukaryotic
      cells. FCVC was nondialyzable, proteinase K-sensitive, and stable to heating at
      <60 degrees C for 5 min. We prepared thiosulfate citrate bile salts sucrose
      (TCBS) plates with FCVC (F-TCBS plates). After confirming that VBNC V. cholerae
      O1 and O139 formed typical yellow colonies on F-TCBS plates, we tried to isolate
      cholera toxin gene-positive VBNC V. cholerae from environmental water samples
      collected in urban slum areas of Kolkata, India and succeeded in isolating V.
      cholerae O1 El Tor variant strains harboring a gene for the cholera toxin. The
      possible importance of VBNC V. cholerae O1 as a source of cholera outbreaks is
      discussed.

PMID- 24574070
TI  - Chemo- and regioselective C(sp3)-H arylation of unactivated allylarenes by
      deprotonative cross-coupling.
AB  - The combination of aryl bromides, allylbenzene, base and a palladium catalyst
      usually results in a Heck reaction. Herein we combine these same reagents, but
      override the Heck pathway by employing a strong base. In the presence of
      LiN(SiMe3)2, allylbenzene derivatives undergo reversible deprotonation.
      Transmetalation of the resulting allyllithium intermediate to LPdAr(Br) and
      reductive elimination provide the 1,1-diarylprop-2-enes, which are not accessible
      by the Heck reaction. The regioselectivity in this deprotonative cross-coupling
      process is catalyst-controlled and very high.

PMID- 24574072
TI  - Computer simulation of flagellar movement X: doublet pair splitting and bend
      propagation modeled using stochastic dynein kinetics.
AB  - Experimental observations on cyclic splitting and bending by a flagellar doublet
      pair are modeled using forces obtained from a model for dynein mechanochemistry,
      based on ideas introduced by Andrew Huxley and Terrill Hill and extended
      previously for modeling flagellar movements. The new feature is elastic
      attachment of dynein to the A doublet, which allows movement perpendicular to the
      A doublet and provides adhesive force that can strain attached dyneins. This
      additional strain influences the kinetics of dynein attachment and detachment.
      Computations using this dynein model demonstrate that very simple and realistic
      ideas about dynein mechanochemistry are sufficient for explaining the separation
      and reattachment seen experimentally with flagellar doublet pairs. Additional
      simulations were performed after adding a "super-adhesion" elasticity. This
      elastic component is intended to mimic interdoublet connections, normally present
      in an intact axoneme, that would prevent visible splitting but allow sufficient
      separation to cause dynein detachment and cessation of shear force generation.
      This is the situation envisioned by Lindemann's "geometric clutch" hypothesis for
      control of dynein function in flagella and cilia. The simulations show abrupt
      disengagement of the "clutch" at one end of a bend, and abrupt reengagement of
      the "clutch" at the other end of a bend, ensuring that active sliding is only
      operating where it will cause bend propagation from base to tip.

PMID- 24574073
TI  - Editorial. Hyperplastic growth and tissue damage.

PMID- 24574071
TI  - Facial emotion processing in borderline personality disorder: a systematic review
      and meta-analysis.
AB  - A body of work has developed over the last 20 years that explores facial emotion
      perception in Borderline Personality Disorder (BPD). We identified 25 behavioural
      and functional imaging studies that tested facial emotion processing differences
      between patients with BPD and healthy controls through a database literature
      search. Despite methodological differences there is consistent evidence
      supporting a negative response bias to neutral and ambiguous facial expressions
      in patients. Findings for negative emotions are mixed with evidence from
      individual studies of an enhanced sensitivity to fearful expressions and impaired
      facial emotion recognition of disgust, while meta-analysis revealed no
      significant recognition impairments between BPD and healthy controls for any
      negative emotion. Mentalizing studies indicate that BPD patients are accurate at
      attributing mental states to complex social stimuli. Functional neuroimaging data
      suggest that the underlying neural substrate involves hyperactivation in the
      amygdala to affective facial stimuli, and altered activation in the anterior
      cingulate, inferior frontal gyrus and the superior temporal sulcus particularly
      during social emotion processing tasks. Future studies must address
      methodological inconsistencies, particularly variations in patients' key clinical
      characteristics and in the testing paradigms deployed. 

PMID- 24574074
TI  - The role of secondhand smoke in sinusitis: a systematic review.
AB  - BACKGROUND: The objective of this study was to systematically review existing
      literature on the association between sinusitis and secondhand smoke (SHS)
      exposure. METHODS: We performed a literature search encompassing the last 25
      years in PubMed, EMBASE, and Cochrane CENTRAL. Inclusion criteria included
      English language papers containing original human data with at least 7 subjects.
      Data was systematically collected on study design, patient demographics, clinical
      characteristics/outcomes, and level-of-evidence (Oxford Center for Evidence-Based
      Medicine). Quality assessment was performed using the Newcastle-Ottawa scale. Two
      investigators independently reviewed all manuscripts. RESULTS: The initial search
      yielded 116 abstracts, of which 19 articles were included. Thirteen (68.4%) of
      the 19 articles showed a statistically significant association between sinusitis
      and SHS. Seven (36.8%) studies specifically evaluated chronic rhinosinusitis
      (CRS) with 5 (71.4%) CRS studies demonstrating a significant association between
      CRS and SHS. Seventeen articles were case-control studies (Level 3b). For
      characterizing sinusitis, 6 (31.6%) studies included computed tomography (CT) or
      endoscopy in the diagnostic criteria, with 5 of these studies following
      rhinosinusitis taskforce guidelines. For determining presence of SHS, all studies
      used questionnaires and 2 (10.5%) studies also reported serum or urine cotinine
      levels. CONCLUSION: A majority of the studies (68.4%) included in this systematic
      review showed a significant association between sinusitis and SHS. Furthermore, 5
      (83.3%) of the 6 studies with objective diagnostic criteria (CT, endoscopy) found
      a significant association between sinusitis and SHS. Further higher-quality
      studies with objective diagnosis of sinusitis and quantification of SHS exposure
      should be performed in the future to better evaluate the relationship between
      sinusitis and SHS.

PMID- 24574075
TI  - Anion effect on the binary and ternary phase diagrams of chiral medetomidine
      salts and conglomerate crystal formation.
AB  - The binary phase diagrams of hydrogen halides salts of medetomidine (Med.HX,
      X:Br,I) and hydrogen oxalate salt of medetomidine (Med.Ox) were determined based
      on thermogravimetric/differential thermal analysis (TGA/DTA) and their crystal
      structure behavior was confirmed by comparison of the X-ray diffractometry and FT
      IR spectroscopy of the racemate and pure enantiomer. All hydrogen halide salts
      presented racemic compound behavior. Heat of fusion of halides salt of (rac)
      medetomidine decreased with ionic radius increase. Eutectic points for Med.HCl
      (previously reported), Med.HBr, and Med.HI rest were unchanged approximately. The
      solubility of different enantiomeric mixtures of Med.HBr and Med.HI were measured
      at 10, 20, and 30 degrees C in 2-propanol showing a solubility increase with
      ionic radius. A binary phase diagram of Med.Ox shows a racemic conglomerate
      behavior. The solubility of enantiomeric mixtures of Med.Ox were measured at 10,
      20, 30, and 40 degrees C. The ternary phase diagram of Med.Ox in ethanol conforms
      to a conglomerate crystal forming system, favoring its enantiomeric purification
      by preferential crystallization.

PMID- 24574078
TI  - Detection of common respiratory viruses in tonsillar tissue of children with
      obstructive sleep apnea.
AB  - BACKGROUND: Early life viral infection is associated with neurogenic inflammation
      that is present in lymphoid tissues of the upper airway in children with
      obstructive sleep apnea (OSA). We hypothesized that viral genomic material is
      present in tonsils of children with OSA. Therefore, we examined tonsils for the
      presence of respiratory viruses' nucleic acids in children with OSA, and in
      children without OSA (undergoing surgery for recurrent throat infections (RI)).
      METHODS: Tonsillar tissue from patients with OSA and RI was subjected to
      multiplex quantitative real time reverse transcription PCR (mqRTPCR), analyzed
      for the presence of common respiratory viruses' genetic material. RESULTS: Fifty
      six patients were included, of whom 34 had OSA (age (years +/- S.D), 4.22 +/-
      1.14) and 22 with RI (4.35 +/- 1.36). Respiratory viruses nucleic acids (24
      detections) were observed in 17 (50%) OSA samples. In contrast, no virus was
      detected in RI samples (relative frequency P<0.0001). Viruses detected, based on
      frequency were Rhinovirus, Adenovirus, human metapneumovirus (hMPV), respiratory
      syncytial virus (RSV), and corona virus. CONCLUSIONS: Respiratory viruses are
      detected in OSA hypertrophic tonsils, suggestive of their role in the evolution
      of tonsillar inflammation and hypertrophy. Early life viral infections may
      contribute to the pathogenesis of pediatric OSA.

PMID- 24574079
TI  - Dosage individualization of warfarin using artificial neural networks.
AB  - BACKGROUND AND OBJECTIVES: Our objective was to explore artificial neural
      networks (ANNs) as a possible tool for dosage individualization of warfarin.
      METHODS: Demographic, clinical, and genetic data were gathered from a previously
      collected cohort of patients with a stable warfarin dosage who were able to
      achieve an observed international normalized ratio of 2-3. Data from a cohort of
      3,415 patients were used to develop an ANN dosing algorithm. Data from another
      cohort of 856 were used to validate the algorithm. The clinical significance of
      the ANN dosing algorithm was evaluated by calculating the percentage of patients
      whose predicted dosage of warfarin was within 20 % of the actual stable
      therapeutic dose. The clinical significance was also compared with a previously
      published dosing algorithm. RESULTS: A feed-forward neural network with three
      layers was able to successfully predict the ideal warfarin dosage in 48 % of the
      patients. The neural network model explained 48 % and 43 % of the dosage
      variability observed among patients in the derivation and validation cohorts,
      respectively. ANN analysis identified several predictors of warfarin dosage
      including race; age; height; weight; cytochrome P450 (CYP)2C9 genotype; VKORC1
      genotype; sulfonamide, azole antifungals, or macrolide administration;
      carbamazepine, phenytoin, or rifampicin administration; and amiodarone
      administration. CONCLUSION: An ANN was applied to develop a warfarin dosing
      algorithm. The proposed dosing algorithm has the potential to recommend warfarin
      dosages that are close to the appropriate dosages.

PMID- 24574080
TI  - Monitoring drug markets in the Internet age and the evolution of drug monitoring
      systems in Australia.
AB  - In Australia, drug monitoring systems have been in place for more than a decade
      allowing for the measurement of ongoing trends in drug use and the detection of
      new drugs. The Drug Trends Unit at the National Drug and Alcohol Research Centre
      monitors drugs through four separate systems. The Illicit Drug Reporting System
      (IDRS) measures the price, purity, and availability of drugs that are primarily
      injected. The Ecstasy and Related Drugs Reporting System (EDRS) monitors
      psychostimulants that are used recreationally. The National Illicit Drugs
      Indicator Project (NIDIP) analyzes indicator data including drug-related
      hospitalizations and deaths. Finally, the Drugs and Emerging Technologies Project
      (DNeT) analyzes the role of the Internet in the procurement and use of novel
      psychoactive substances. This paper provides an overview of each component of the
      system, demonstrating how the system has evolved over time.

PMID- 24574082
TI  - Psychological therapies (Internet-delivered) for the management of chronic pain
      in adults.
AB  - BACKGROUND: Chronic pain (i.e. pain lasting longer than three months) is common.
      Psychological therapies (e.g. cognitive behavioural therapy) can help people to
      cope with pain, depression and disability that can occur with such pain.
      Treatments currently are delivered via hospital out-patient consultation (face-to
      face) or more recently through the Internet. This review looks at the evidence
      for psychological therapies delivered via the Internet for adults with chronic
      pain. OBJECTIVES: Our objective was to evaluate whether Internet-delivered
      psychological therapies improve pain symptoms, reduce disability, and improve
      depression and anxiety for adults with chronic pain. Secondary outcomes included
      satisfaction with treatment/treatment acceptability and quality of life. SEARCH
      METHODS: We searched CENTRAL (Cochrane Library), MEDLINE, EMBASE and PsycINFO
      from inception to November 2013 for randomised controlled trials (RCTs)
      investigating psychological therapies delivered via the Internet to adults with a
      chronic pain condition. Potential RCTs were also identified from reference lists
      of included studies and relevant review articles. In addition, RCTs were also
      searched for in trial registries. SELECTION CRITERIA: Peer-reviewed RCTs were
      identified and read in full for inclusion. We included studies if they used the
      Internet to deliver the primary therapy, contained sufficient psychotherapeutic
      content, and promoted self-management of chronic pain. Studies were excluded if
      the number of participants in any arm of the trial was less than 20 at the point
      of extraction. DATA COLLECTION AND ANALYSIS: Fifteen studies met the inclusion
      criteria and data were extracted. Risk of bias assessments were conducted for all
      included studies. We categorised studies by condition (headache or non-headache
      conditions). Four primary outcomes; pain symptoms, disability, depression, and
      anxiety, and two secondary outcomes; satisfaction/acceptability and quality of
      life were extracted for each study immediately post-treatment and at follow-up
      (defined as 3 to 12 months post-treatment). MAIN RESULTS: Fifteen studies (N=
      2012) were included in analyses. We assessed the risk of bias for included
      studies as low overall. We identified nine high 'risk of bias' assessments, 22
      unclear, and 59 low 'risk of bias' assessments. Most judgements of a high risk of
      bias were due to inadequate reporting.Analyses revealed seven effects.
      Participants with headache conditions receiving psychological therapies delivered
      via the Internet had reduced pain (number needed to treat to benefit = 2.72, risk
      ratio 7.28, 95% confidence interval (CI) 2.67 to 19.84, p < 0.01) and a moderate
      effect was found for disability post-treatment (standardised mean difference
      (SMD) -0.65, 95% CI -0.91 to -0.39, p < 0.01). However, only two studies could be
      entered into each analysis; hence, findings should be interpreted with caution.
      There was no clear evidence that psychological therapies improved depression or
      anxiety post-treatment (SMD -0.26, 95% CI -0.87 to 0.36, p > 0.05; SMD -0.48, 95%
      CI -1.22 to 0.27, p > 0.05), respectively. In participants with non-headache
      conditions, psychological therapies improved pain post-treatment (p < 0.01) with
      a small effect size (SMD -0.37, 95% CI -0.59 to -0.15), disability post-treatment
      (p < 0.01) with a moderate effect size (SMD -0.50, 95% CI -0.79 to -0.20), and
      disability at follow-up (p < 0.05) with a small effect size (SMD -0.15, 95% CI 
      0.28 to -0.01). However, the follow-up analysis included only two studies and
      should be interpreted with caution. A small effect was found for depression and
      anxiety post-treatment (SMD -0.19, 95% CI -0.35 to -0.04, p < 0.05; SMD -0.28,
      95% CI -0.49 to -0.06, p < 0.01), respectively. No clear evidence of benefit was
      found for other follow-up analyses. Analyses of adverse effects were not
      possible.No data were presented on satisfaction/acceptability. Only one study
      could be included in an analysis of the effect of psychological therapies on
      quality of life in participants with headache conditions; hence, no analysis
      could be undertaken. Three studies presented quality of life data for
      participants with non-headache conditions; however, no clear evidence of benefit
      was found (SMD -0.27, 95% CI -0.54 to 0.01, p > 0.05). AUTHORS' CONCLUSIONS:
      There is insufficient evidence to make conclusions regarding the efficacy of
      psychological therapies delivered via the Internet in participants with headache
      conditions. Psychological therapies reduced pain and disability post-treatment;
      however, no clear evidence of benefit was found for depression and anxiety. For
      participants with non-headache conditions, psychological therapies delivered via
      the Internet reduced pain, disability, depression, and anxiety post-treatment.
      The positive effects on disability were maintained at follow-up. These effects
      are promising, but considerable uncertainty remains around the estimates of
      effect. These results come from a small number of trials, with mostly wait-list
      controls, no reports of adverse events, and non-clinical recruitment methods. Due
      to the novel method of delivery, the satisfaction and acceptability of these
      therapies should be explored in this population. These results are similar to
      those of reviews of traditional face-to-face therapies for chronic pain.

PMID- 24574083
TI  - c-fos and c-jun expression in the liver of silver carp and the effect of
      microcystins.
AB  - In the present study, c-fos and c-jun cDNAs were cloned, and their phylogenetic
      trees were constructed. The results demonstrate that the full-length c-fos cDNA
      is 1719 bp and contains a 1059-bp open reading frame (ORF) encoding 352 amino
      acids. The c-jun cDNA is 1931 bp and contains a 927-bp ORF encoding 308 amino
      acids. Moreover, constitutive expression of c-fos and c-jun was detected in all
      examined tissues of the silver carp using quantitative real-time polymerase chain
      reaction, and the liver showed the highest relative expression rate. In addition,
      we found that either 50 or 200 MUg/kg crude microcystin exposure significantly
      promoted the transcription of c-fos, c-jun, and c-myc in the silver carp liver,
      suggesting that c-fos, c-jun, and c-myc may be involved in the hepatotoxicity of
      microcystins. 

PMID- 24574081
TI  - Hyperphagia: current concepts and future directions proceedings of the 2nd
      international conference on hyperphagia.
AB  - OBJECTIVE: Hyperphagia is a central feature of inherited disorders (e.g., Prader
      Willi Syndrome) in which obesity is a primary phenotypic component. Hyperphagia
      may also contribute to obesity as observed in the general population, thus
      raising the potential importance of common underlying mechanisms and treatments.
      Substantial gaps in understanding the molecular basis of inherited hyperphagia
      syndromes are present as are a lack of mechanistic of mechanistic targets that
      can serve as a basis for pharmacologic and behavioral treatments. DESIGN AND
      METHODS: International conference with 28 experts, including scientists and
      caregivers, providing presentations, panel discussions, and debates. RESULTS: The
      reviewed collective research and clinical experience provides a critical body of
      new and novel information on hyperphagia at levels ranging from molecular to
      population. Gaps in understanding and tools needed for additional research were
      identified. CONCLUSIONS: This report documents the full scope of important topics
      reviewed at a comprehensive international meeting devoted to the topic of
      hyperphagia and identifies key areas for future funding and research.

PMID- 24574084
TI  - Advances in longitudinal studies of amnestic mild cognitive impairment and
      Alzheimer's disease based on multi-modal MRI techniques.
AB  - Amnestic mild cognitive impairment (aMCI) is a prodromal stage of Alzheimer's
      disease (AD), and 75%-80% of aMCI patients finally develop AD. So, early
      identification of patients with aMCI or AD is of great significance for
      prevention and intervention. According to cross-sectional studies, it is known
      that the hippocampus, posterior cingulate cortex, and corpus callosum are key
      areas in studies based on structural MRI (sMRI), functional MRI (fMRI), and
      diffusion tensor imaging (DTI) respectively. Recently, longitudinal studies using
      each MRI modality have demonstrated that the neuroimaging abnormalities generally
      involve the posterior brain regions at the very beginning and then gradually
      affect the anterior areas during the progression of aMCI to AD. However, it is
      not known whether follow-up studies based on multi-modal neuroimaging techniques
      (e.g., sMRI, fMRI, and DTI) can help build effective MRI models that can be
      directly applied to the screening and diagnosis of aMCI and AD. Thus, in the
      future, large-scale multi-center follow-up studies are urgently needed, not only
      to build an MRI diagnostic model that can be used on a single person, but also to
      evaluate the variability and stability of the model in the general population. In
      this review, we present longitudinal studies using each MRI modality separately,
      and then discuss the future directions in this field.

PMID- 24574085
TI  - Nasal saline irrigation has no effect on normal olfaction: a prospective
      randomized trial.
AB  - BACKGROUND: Nasal saline irrigation is a safe treatment for chronic
      rhinosinusitis; however, its effect on olfaction is unclear. Cyclic adenosine
      monophosphate (cAMP) is a key second messenger in the mechanism of olfaction and
      has been shown to be associated with smell function. In animal studies, olfactory
      cilia may be harvested by simple saline preparations. This study aimed to
      characterize the effect of nasal saline irrigation on smell function. METHODS:
      Volunteers with normal olfaction were randomized into a control or irrigation
      cohort. In the initial appointment, subjects completed a University of
      Pennsylvania Smell Identification Test (UPSIT) and nasal samples were obtained by
      2 methods: the nasal curette and cytobrush. The irrigation cohort performed daily
      nasal saline irrigations. Both cohorts then returned in 1 week. The UPSIT and
      nasal cell collection were repeated, and each subject completed a subjective
      olfactory transition scale. Nasal samples were processed for cAMP levels using a
      commercial assay. RESULTS: Thirty-two subjects were enrolled and randomized into
      each cohort. Control and postirrigation mean UPSIT scores were 36.8 and 36.7 (p =
      0.48). No subjects reported a subjective smell loss. Ten pairs of nasal samples
      were assayed. Using the curette, control and postirrigation cAMP levels were 509
      and 490 fmol/(mg/mL), respectively (p = 0.94). Using the cytobrush, respective
      cAMP levels were 424 and 449 fmol/(mg/mL), respectively (p = 0.94). CONCLUSION:
      Nasal saline irrigation has no subjective or objective effect on olfaction. It
      also does not appear to affect cAMP levels, a potential marker of smell function.

PMID- 24574086
TI  - Fat and whey supplementation influence milk composition, backfat loss, and
      reproductive performance in lactating sows.
AB  - This study investigates the effects of microencapsulated fat (FAT) and whey
      protein (WHEY) supplementation on the milk composition, backfat loss, and
      reproductive performance in lactating sows. A total of 144 sows were divided
      according to their backfat thickness at farrowing into three groups, i.e., low
      (12.0-16.5 mm, n = 33), moderate (17.0-21.5 mm, n = 78), and high (22.0-24.5 mm,
      n = 33). The lactation diet was divided into three types, i.e., a control diet
      (CONTROL, n = 50), a diet supplemented with FAT (n = 48), and a diet supplemented
      with WHEY (n = 50). Pooled milk samples were collected at the second and third
      week of lactation. On average, the sows lost backfat 23.5 % during lactation. The
      backfat loss during lactation was 24.5, 22.7, and 22.8 % in sows fed with
      CONTROL, FAT, and WHEY diets, respectively (P > 0.05). Supplementation of FAT
      increased the percentage of fat in the sow's milk compared to the CONTROL (9.1
      and 8.4 %, P = 0.022). For sows with low backfat, FAT and WHEY supplementation
      increased the average daily gain of piglets compared to the CONTROL (244, 236,
      and 205 g/days, respectively, P < 0.05). For sows with high backfat, the sows
      receiving the CONTROL diet had a higher total piglet mortality than those that
      received FAT or WHEY (28.1, 14.1, and 13.0 %, respectively, P < 0.05). It could
      be concluded that supplementation of FAT in the diet of sow during lactation
      significantly enhanced the fat content in the sow's milk, improved the piglet's
      daily weight gain, and reduced piglet mortality. 

PMID- 24574087
TI  - Insights into the effects of disease-causing mutations in human actins.
AB  - Mutations in all six actins in humans have now been shown to cause diseases.
      However, a number of factors have made it difficult to gain insight into how the
      changes in actin functions brought about by these pathogenic mutations result in
      the disease phenotype. These include the presence of multiple actins in the same
      cell, limited accessibility to pure mutant material, and complexities associated
      with the structures and their component cells that manifest the diseases. To try
      to circumvent these difficulties, investigators have turned to the use of model
      systems. This review describes these various approaches, the initial results
      obtained using them, and the insight they have provided into allosteric
      mechanisms that govern actin function. Although results so far have not explained
      a particular disease phenotype at the molecular level, they have provided
      valuable insight into actin function at the mechanistic level which can be
      utilized in the future to delineate the molecular bases of these different
      actinopathies.

PMID- 24574089
TI  - Unexpected formation of a [4]radialene and dendralenes by addition of
      tetracyanoethylene to a tetraaryl[5]cumulene.
AB  - The use of cumulenes in synthetic transformations offers the possibility to form
      structurally interesting and potentially useful conjugated molecules. The
      cycloaddition reaction of a tetraaryl[5]cumulene with the electron-deficient
      olefin tetracyanoethylene affords unusual products, including functionalized
      dendralenes and alkylidene cyclobutanes, as well as a symmetric [4]radialene that
      shows unique solvatochromism, with lambda(max) values approaching the near-IR
      region. These carbon-rich products have been investigated spectroscopically and
      by X-ray crystallographic analysis (five structures). The cycloaddition reaction
      sequence has also been explored by mechanistic and theoretical studies. The
      obtained results clearly demonstrate the potential of [5]cumulenes to serve as
      precursors for unprecedented conjugated structures.

PMID- 24574091
TI  - On the efficiency of charge transfer state splitting in polymer:fullerene solar
      cells.
AB  - The field dependence and yield of free charge carrier generation in
      polymer:fullerene blends with varying energetic offsets is not affected when the
      excitation energy is varied from above band-gap to direct CT state excitation.
      Instead, the ability of the CT state to split is dictated by the energetic offset
      between the relaxed CT state and the charge separated (CS) state. 

PMID- 24574090
TI  - Patient positioning and prevention of injuries in patients undergoing
      laparoscopic and robot-assisted urologic procedures.
AB  - Positioning injuries in the perioperative period are one of the inherent risks of
      surgery, but particularly in robot-assisted urologic surgery, and can result in
      often unrecognized morbidity. Injuries such as upper or lower extremity
      peripheral neuropathies occur via neural mechanisms and injuries such as
      compartment syndrome, rhabdomyolysis, ischemic optic neuropathy, and acute
      arterial occlusion occur via vascular mechanisms. The risk of injury may be
      exacerbated by operative and patient-related risk factors. Patient-related risk
      factors include ASA class and BMI, while surgery-related risk factors include
      physical orientation of the patient and operative length. These injuries can be
      prevented or reduced by joint effort of the surgeon, anesthesiologist, and
      operating room staff. 

PMID- 24574092
TI  - Accuracy of tidal breathing measurement of FloRight compared to an ultrasonic
      flowmeter in infants.
AB  - INTRODUCTION: Monitoring breathing pattern is especially relevant in infants with
      lung disease. Recently, a vest-based inductive plethysmograph system
      (FloRight(r)) has been developed for tidal breathing measurement in infants. We
      investigated the accuracy of tidal breathing flow volume loop (TBFVL)
      measurements in healthy term-born infants and infants with lung disease by the
      vest-based system in comparison to an ultrasonic flowmeter (USFM) with a face
      mask. We also investigated whether the system discriminates between healthy
      infants and those with lung disease. METHODS: Floright(r) measures changes in
      thoracoabdominal volume during tidal breathing through magnetic field changes
      generated by current-carrying conductor coils in an elastic vest. Simultaneous
      TBFVL measurements by the vest-based system and the USFM were performed at 44
      weeks corrected postmenstrual age during quiet unsedated sleep. TBFVL parameters
      derived by both techniques and within both groups were compared. RESULTS: We
      included 19 healthy infants and 18 infants with lung disease. Tidal volume per
      body weight derived by the vest-based system was significantly lower with a mean
      difference (95% CI) of -1.33 ml/kg (-1.73; -0.92), P < 0.001. Respiratory rate
      and ratio of time to peak tidal expiratory flow over total expiratory time
      (tPTEF/tE) did not differ between the two techniques. Both systems were able to
      discriminate between healthy infants and those with lung disease using tPTEF/tE.
      CONCLUSION: FloRight(r) accurately measures time indices and may discriminate
      between healthy infants and those with lung disease, but demonstrates differences
      in tidal volume measurements. It may be better suited to monitor breathing
      pattern than for TBFVL measurements.

PMID- 24574093
TI  - Lessons learned in andrology: what I have learned.

PMID- 24574094
TI  - Effects of prenatal and lactation nicotine exposure on rat testicular
      interstitial tissue.
AB  - Nicotine is largely consumed as a component of cigarettes. It induces apoptosis,
      interferes with endocrine function by changing the sex hormones secretion and
      leads to male infertility. Testosterone is produced from cholesterol by Leydig
      cells (LC), with the participation of testicular macrophages (MO). Thus, to
      investigate whether nicotine administration to pregnant and lactating rats
      changes cholesterol and sexual hormone levels and LC and MO populations of
      offspring, female rats received nicotine (2 mg/kg/day) through osmotic minipumps
      from the first day of pregnancy up to the end of weaning. At 1, 30, 60 and 90
      days post-partum (dpp) the plasma cholesterol and testosterone levels were
      obtained, as well as the biometric, histopathological and stereological
      testicular parameters. Nicotine reduced the body weight, cholesterol levels and
      lipid droplet number in foetal LC at 1 dpp. The number of apoptotic LC did not
      change in the offspring of nicotine group at any age studied. No alterations in
      the numerical densities of MO and LC occurred at 60 and 90 dpp. Hypertrophy of
      mature LC and increase in cholesterol and testosterone levels were noted at 90
      dpp. In conclusion, nicotine when administered to rats throughout pregnancy and
      lactation induces morphofunctional alterations of foetal and mature LC and
      affects cholesterol and testosterone levels.

PMID- 24574095
TI  - Adipose tissue-derived stem cell therapy for prevention and treatment of erectile
      dysfunction in a rat model of Peyronie's disease.
AB  - Peyronie's disease (PD) is a localized connective tissue disorder that involves
      the tunica albuginea (TA) of the penis. While surgical correction remains the
      gold standard, the search for an effective and less invasive therapy continues.
      The objective of this study was to evaluate the effects of intratunical injection
      of adipose tissue-derived stem cells (ADSCs) for the prevention and treatment of
      erectile dysfunction in a rat model of PD. Twenty-four male Sprague-Dawley rats
      (300-350 g) were randomly divided into four groups: sham, PD, PD + ADSC
      (prevention) and PD + ADSC (treatment). All rats underwent penile injections into
      the TA with 50 MUL vehicle (sham) or 0.5 MUg transforming growth factor (TGF)
      beta1 (remaining groups). The ADSC groups received intratunical injections with
      0.5 million rat-labelled ADSCs on day 0 (prevention) or day 30 (treatment). Forty
      five days following TGF-beta1 injection, rats underwent cavernous nerve
      stimulation (CNS) with total intracavernous-to-mean arterial pressure ratio
      (ICP/MAP) and total ICP recorded to measure response to therapy. Tissues were
      evaluated histologically and for mRNA expression of tissue inhibitors of
      metalloproteinases (TIMPs), matrix metalloproteinases (MMPs) and zymographic
      activity of MMPs. Statistical analysis was performed by analysis of variance
      followed by the Tukey test for post hoc comparisons. In both prevention and
      treatment groups, intratunical injection of ADSCs resulted in significantly
      higher ICP/MAP and total ICP in response to CNS compared with the PD group. Local
      injection of ADSCs prevented and/or reduced Peyronie's-like changes by decreasing
      the expression of TIMPs, and stimulating expression and activity of MMPs. This
      study documents the preventive and therapeutic benefits of ADSC on penile
      fibrosis and erectile function in an animal model of PD.

PMID- 24574097
TI  - Television's "crazy lady" trope: female psychopathic traits, teaching, and
      influence of popular culture.
AB  - OBJECTIVE: This article describes notable illustrations of female psychopathy on
      modern television to review various characters that will have utility in teaching
      students about female psychopathy in distinction to male psychopathy and to
      encourage consideration of the potential effects that viewing these countless
      examples may have on a generation of young women. METHODS: The authors use
      examples from soap operas, crime procedurals, reality television, fantasy,
      comedies, and young adult programs to illustrate gender differences in
      psychopathy and make specific teaching points. They also review the research
      literature related to popular culture's impact on behavior and gender roles.
      RESULTS: Gender differences in real-world psychopathy are mirrored in television
      portrayals. For example, female psychopaths, on TV and in reality, use sexual
      manipulation, demonstrate unstable emotions, and employ social aggression to
      achieve their ambitions. The examples of female psychopathic traits are prevalent
      on TV and easily accessible for teaching purposes. Research does give some
      support for a popular culture impact on behavior and gender roles. CONCLUSIONS:
      As compared to male psychopathy, female psychopathy is less recognized, and there
      are some notable differences in how the psychopathic traits manifest. Television
      provides myriad teaching examples that can highlight the gender distinctions such
      as use of sexual manipulation, emotional instability, and social aggression.
      Research suggests that the prevalence of "crazy ladies" on television may be
      negatively impacting gender stereotypes and normalizing bad behavior in young
      women.

PMID- 24574096
TI  - Dynamic Hedgehog signalling pathway activity in germline stem cells.
AB  - Although the contribution of Hedgehog (Hh) signalling to stem cell development
      and oncogenesis is well recognised, its importance for spermatogonial stem cells
      (SSCs) has not been established. Here we interrogate adult rat SSCs using an
      established model in which only undifferentiated spermatogonial cells remain in
      the testis at 15 weeks following irradiation, and spermatogonial differentiation
      is induced within 4 weeks by gonadotrophin-releasing hormone antagonist (GnRH
      ant) administration. Synthesis of Hh pathway components in untreated adult rat
      testes was compared with that in irradiated testes prior to and after GnRH-ant
      exposure using in situ hybridization. In adult testes with complete
      spermatogenesis, the Desert Hedgehog ligand transcript, Dhh, was detected in
      Sertoli cells, some spermatogonia and in spermatocytes by in situ hybridization.
      Spermatogenic cells were identified as sites of Hh signalling through detection
      of transcripts encoding the Hh receptor, Ptc2 transcripts and proteins for the
      key downstream target of Hh signalling, Gli1 and the Hh transcriptional
      activator, Gli2. Remarkably, the undifferentiated spermatogonia present in
      irradiated adult rat testes contained Dhh in addition to Ptc2, Gli1 and Gli2,
      revealing the potential for an autocrine Hh signalling loop to sustain
      undifferentiated spermatogonial cells. These transcripts became undetectable by
      in situ hybridization following GnRH-ant induction of spermatogonial
      differentiation, however, detection of Gli1 protein in spermatogonia in all
      groups indicates that Hh signalling is sustained. This is the first evidence of
      active Hh signalling in mammalian male germline stem cells, as has been
      documented for some cancer stem cells.

PMID- 24574098
TI  - Integrating neuroscience in the training of psychiatrists: a patient-centered
      didactic curriculum based on adult learning principles.
AB  - OBJECTIVE: The authors describe the development and implementation of a new adult
      psychiatry residency didactic curriculum based on adult learning principles and
      an integrative, patient-centered approach that includes a progressive 4-year
      neuroscience curriculum. METHOD: The authors describe the process of conducting a
      needs assessment, engaging stakeholders and developing guiding principles for the
      new curriculum. The curriculum was evaluated using qualitative measures, a
      resident survey, course evaluations, and a pilot version of a specialized
      assessment tool. RESULTS: Feedback from the resident survey and from course
      evaluations was positive, and residents indicated interest in receiving
      additional training in neuroscience. Residents self-reported not incorporating
      neuroscience into formulation and treatment planning as often as other
      perspectives. They also reported that neuroscience was reinforced less by
      clinical faculty than other perspectives. Performance on the curriculum
      assessment corroborated that clinical application of neuroscience may benefit
      from additional reinforcement. CONCLUSIONS: Residents responded well to the
      design and content of the new didactic curriculum. The neuroscience component
      appears to have achieved its primary objective of enhancing attitudes to the
      field. Continued work including enhancing the culture of neuroscience at the
      clinical sites may be required to achieve broader behavioral goals.

PMID- 24574099
TI  - Mechanical versus manual chest compressions for cardiac arrest.
AB  - BACKGROUND: This is the first update of the Cochrane review on mechanical chest
      compression devices published in 2011 (Brooks 2011). Mechanical chest compression
      devices have been proposed to improve the effectiveness of cardiopulmonary
      resuscitation (CPR). OBJECTIVES: To assess the effectiveness of mechanical chest
      compressions versus standard manual chest compressions with respect to
      neurologically intact survival in patients who suffer cardiac arrest. SEARCH
      METHODS: We searched the Cochrane Central Register of Controlled Studies
      (CENTRAL; 2013, Issue 12), MEDLINE Ovid (1946 to 2013 January Week 1), EMBASE
      (1980 to 2013 January Week 2), Science Citation abstracts (1960 to 18 November
      2009), Science Citation Index-Expanded (SCI-EXPANDED) (1970 to 11 January 2013)
      on Thomson Reuters Web of Science, biotechnology and bioengineering abstracts
      (1982 to 18 November 2009), conference proceedings Citation Index-Science (CPCI
      S) (1990 to 11 January 2013) and clinicaltrials.gov (2 August 2013). We applied
      no language restrictions. Experts in the field of mechanical chest compression
      devices and manufacturers were contacted. SELECTION CRITERIA: We included
      randomised controlled trials (RCTs), cluster RCTs and quasi-randomised studies
      comparing mechanical chest compressions versus manual chest compressions during
      CPR for patients with atraumatic cardiac arrest. DATA COLLECTION AND ANALYSIS:
      Two review authors abstracted data independently; disagreement between review
      authors was resolved by consensus and by a third review author if consensus could
      not be reached. The methodologies of selected studies were evaluated by a single
      author for risk of bias. The primary outcome was survival to hospital discharge
      with good neurological outcome. We planned to use RevMan 5 (Version 5.2. The
      Nordic Cochrane Centre) and the DerSimonian & Laird method (random-effects model)
      to provide a pooled estimate for risk ratio (RR) with 95% confidence intervals
      (95% CIs), if data allowed. MAIN RESULTS: Two new studies were included in this
      update. Six trials in total, including data from 1166 participants, were included
      in the review. The overall quality of included studies was poor, and significant
      clinical heterogeneity was observed. Only one study (N = 767) reported survival
      to hospital discharge with good neurological function (defined as a Cerebral
      Performance Category score of one or two), demonstrating reduced survival with
      mechanical chest compressions when compared with manual chest compressions (RR
      0.41, 95% CI 0.21 to 0.79). Data from four studies demonstrated increased return
      of spontaneous circulation, and data from two studies demonstrated increased
      survival to hospital admission with mechanical chest compressions as compared
      with manual chest compressions, but none of the individual estimates reached
      statistical significance. Marked clinical heterogeneity between studies precluded
      any pooled estimates of effect. AUTHORS' CONCLUSIONS: Evidence from RCTs in
      humans is insufficient to conclude that mechanical chest compressions during
      cardiopulmonary resuscitation for cardiac arrest are associated with benefit or
      harm. Widespread use of mechanical devices for chest compressions during cardiac
      events is not supported by this review. More RCTs that measure and account for
      the CPR process in both arms are needed to clarify the potential benefit to be
      derived from this intervention.

PMID- 24574100
TI  - The syntheses, characterization and in vitro metabolism of nitracaine,
      methoxypiperamide and mephtetramine.
AB  - Three legal highs; nitracaine (3-(diethylamino)-2,2-dimethylpropyl 4
      nitrobenzoate), methoxypiperamide (MEOP, (4-methoxyphenyl)(4-methylpiperazin-1
      yl)methanone) and mephtetramine (MTTA, 2-((methylamino)methyl)-3,4
      dihydronaphthalen-1(2H)-one) appeared in 2013 as new psychoactive substances
      (NPS) on Internet websites selling 'research chemicals'. These compounds were
      synthesized and analyzed via our synthesize, analyze, and metabolize (SAM)
      protocol. Nitracaine was synthesized by the transesterification of methyl 4
      nitrobenzoate with 3-(diethylamino)-2,2-dimethylpropan-1-ol. Methoxypiperamide
      was synthesized by the reaction of 4-methoxybenzoyl chloride with 1
      methylpiperazine, and mephtetramine through the Mannich reaction of 1-tetralone
      with paraformaldehyde and methylamine hydrochloride. Each compound was
      characterized by nuclear magnetic resonance (NMR), gas chromatography with
      electron impact mass spectrometry (GC-EIMS), liquid chromatography-electrospray
      ionization-mass spectrometry (LC-ESI-MS), and high resolution electrospray
      ionization mass spectrometry (HR-ESI-MS). A sample of nitracaine was also test
      purchased from an Internet vendor and its structure confirmed by GC-EIMS and LC
      ESI-MS. Finally, the in vitro metabolism of the nitracaine, mephtetramine, and
      methoxypiperamide was investigated, using a human microsomal liver extract, in
      order to tentatively identify potential metabolites that may be encountered in
      the analysis of biological samples in clinical or toxicology labs. The use of our
      SAM protocol highlights the ability of academic research labs to quickly respond
      to and disseminate information about emerging NPS.

PMID- 24574102
TI  - Medication adherence part two: predictors of nonadherence and adherence.
AB  - PURPOSE: This is the second of a three-part series on medication adherence in
      which the authors describe the continuum of adherence to nonadherence of
      medication usage. DATA SOURCES: Research articles through MEDLINE and PubMed.
      CONCLUSIONS: Understanding the magnitude and scope of the problem of medication
      nonadherence is the first step in reaching better adherence rates (described in
      Part One of this series). The second step is to recognize the complexities of the
      reasons for medication adherence/nonadherence (described here). Reasons for
      nonadherence include beliefs related to the benefits of medication for physical
      and mental disorders, complexities of systems of health care and treatment plans,
      and lifestyle and demographic characteristics of patients. The final step is to
      evaluate each patient for medication adherence, tailoring the plan of care
      according to patient and system specific barriers (described in Part Three of
      this series). IMPLICATIONS FOR PRACTICE: Nurse practitioners must recognize a
      critical element of thorough care is to assess medication adherence at each
      patient visit, countering patient and system barriers as indicated. Nurse
      practitioners also need to adjust assessment and prescribing practices according
      to the evidence for best practices to improve medication adherence.

PMID- 24574101
TI  - Characterization of conjugated polymer actuation under cerebral physiological
      conditions.
AB  - Conjugated polymer actuators have potential use in implantable neural interface
      devices for modulating the position of electrode sites within brain tissue or
      guiding insertion of neural probes along curved trajectories. The actuation of
      polypyrrole (PPy) doped with dodecylbenzenesulfonate (DBS) is characterized to
      ascertain whether it can be employed in the cerebral environment. Microfabricated
      bilayer beams are electrochemically cycled at either 22 or 37  degrees C in
      aqueous NaDBS or in artificial cerebrospinal fluid (aCSF). Nearly all the ions in
      aCSF are exchanged into the PPy-the cations Na(+) , K(+) , Mg(2+) , Ca(2+) , as
      well as the anion PO4 (3-) ; Cl(-) is not present. Nevertheless, deflections in
      aCSF are comparable to those in NaDBS and they are monotonic with oxidation
      level: strain increases upon reduction, with no reversal of motion despite the
      mixture of ionic charges and valences being exchanged. Actuation depends on
      temperature. Upon warming, the cyclic voltammograms show additional peaks and an
      increase of 70% in the consumed charge. Bending is, however, much less affected:
      strain increases somewhat (6%-13%) but remains monotonic, and deflections shift
      (up to 20%). These results show how the actuation environment must be taken into
      account, and demonstrate proof of concept for actuated implantable neural
      interfaces. 

PMID- 24574103
TI  - An evaluation of Knowledge and Understanding Framework personality disorder
      awareness training: can a co-production model be effective in a local NHS mental
      health Trust?
AB  - 5 Boroughs Partnership NHS Foundation Trust, in the Northwest of England, has
      trained over 500 staff in the Knowledge and Understanding Framework, level 1
      personality disorder awareness training. This is a 3-day nationally devised
      training programme delivered via an innovative co-production model (i.e. co
      delivery and partnership working with service users who have lived experience).
      This paper provides quantitative and qualitative information on the effectiveness
      of training delivery and also serves to provide some insight into the impact of
      service-user involvement via such a co-production model. Information on 162
      participants using the Knowledge and Understanding Framework bespoke
      questionnaire (Personality Disorder Knowledge, Attitudes and Skills
      Questionnaire) suggests that the training can be effectively delivered by and
      within a local NHS Mental Health Trust. Results immediately post-training suggest
      an improvement in levels of understanding and capability efficacy and a reduction
      in negative emotional reactions. Indications from a 3-month follow-up suggest
      that while understanding and emotional reaction remain improved, capability
      efficacy regresses back to pre-training levels, suggesting the need for ongoing
      supervision and/or support to consolidate skills. Discussion includes guidelines
      for the implementation of a truly integrated co-production model of training
      provision, as well as advice relating to the maximization of long-term benefits.

PMID- 24574104
TI  - Increased nitrogen leaching following soil freezing is due to decreased root
      uptake in a northern hardwood forest.
AB  - The depth and duration of snow pack is declining in the northeastern United
      States as a result of warming air temperatures. Since snow insulates soil, a
      decreased snow pack can increase the frequency of soil freezing, which has been
      shown to have important biogeochemical implications. One of the most notable
      effects of soil freezing is increased inorganic nitrogen losses from soil during
      the following growing season. Decreased nitrogen retention is thought to be due
      to reduced root uptake, but has not yet been measured directly. We conducted a 2
      year snow-removal experiment at Hubbard Brook Experimental Forest in New
      Hampshire, USA to determine the effects of soil freezing on root uptake and
      leaching of inorganic nitrogen simultaneously. Snow removal significantly
      increased the depth of maximal soil frost by 37.2 and 39.5 cm in the first and
      second winters, respectively (P < 0.001 in 2008/2009 and 2009/2010). As a
      consequence of soil freezing, root uptake of ammonium declined significantly
      during the first and second growing seasons after snow removal (P = 0.023 for
      2009 and P = 0.005 for 2010). These observed reductions in root nitrogen uptake
      coincided with significant increases in soil solution concentrations of ammonium
      in the Oa horizon (P = 0.001 for 2009 and 2010) and nitrate in the B horizon (P <
      0.001 and P = 0.003 for 2009 and 2010, respectively). The excess flux of
      dissolved inorganic nitrogen from the Oa horizon that was attributable to soil
      freezing was 7.0 and 2.8 kg N ha(-1) in 2009 and 2010, respectively. The excess
      flux of dissolved inorganic nitrogen from the B horizon was lower, amounting to
      1.7 and 0.7 kg N ha(-1) in 2009 and 2010, respectively. Results of this study
      provide direct evidence that soil freezing reduces root nitrogen uptake,
      demonstrating that the effects of winter climate change on root function has
      significant consequences for nitrogen retention and loss in forest ecosystems.

PMID- 24574105
TI  - The mental health of the UK Armed Forces in the 21st century: resilience in the
      face of adversity.
AB  - The recent conflicts in Iraq and Afghanistan have attracted considerable
      political and media interest in the mental health of UK military personnel. As a
      result of the close operational collaboration between US and UK forces, there
      have inevitably been many comparisons drawn between the mental health status of
      the two forces. Considerable research activity suggests that the mental health of
      UK forces appear to have remained relatively resilient in spite of their
      considerable exposure to traumatic events; one stark exception to this is the
      high rates of alcohol misuse which seem to be related to deployment. This paper
      explores the recently published literature relating to UK military forces and
      attempts to draw conclusions about the reasons for the apparent resilience shown
      by the majority of the regular forces. 

PMID- 24574106
TI  - Combat Casualty Care research programme.
AB  - The Combat Casualty Care research programme is an integrated suite of projects
      designed to address Defence Medical Services' research needs for casualty care.
      The programme covers a broad spectrum of topics ranging from the
      pathophysiological and immunological impact of military relevant injuries to the
      effects of these disturbances on the response to early treatment. Dstl Porton
      Down has a long history of studying military injuries and has developed models,
      both in vivo and physical, to address the research needs. The work is conducted
      in close collaboration with clinical colleagues at the Royal Centre for Defence
      Medicine who have direct experience of the clinical issues faced by combat
      casualties and insights into the potential clinical implications of emerging
      strategies. This article reviews progress in research areas spanning forward
      resuscitation, with a particular focus on blast-related injuries, trauma
      coagulopathy, effects of drugs on the response to haemorrhage and deployed
      research. A significant 'value added' component has been the underpinning of
      higher degrees for seconded military clinicians at Dstl Porton Down who have made
      a valuable contribution to the overall programme. 

PMID- 24574109
TI  - PFO and ASD Closure in Adulthood: Where Do We Stand?
AB  - OPINION STATEMENT: Ever since the observation was made linking a higher
      prevalence of a patent foramen ovale (PFO) in younger individuals with
      cryptogenic stroke (CS), there has been a vigorous debate as to the role the PFO
      plays and a search for the optimal management strategy to prevent recurrent CS.
      Data from observational studies from the past two decades have demonstrated the
      superiority of percutaneous device closure over medical therapy. The recent
      publication of three randomized controlled trials (RCTs), which failed to
      demonstrate the superiority of percutaneous closure has reignited the controversy
      as to how best treat these patients. In this article, we will review the
      contemporary literature from the past three years including the results from new
      meta-analyses of medical therapy and device closure. In addition, we will review
      the three published randomized control trials to date (ie, CLOSURE I, the PC
      trial, and RESPECT) along with a meta-analysis of their results. While on primary
      intention-to-treat analysis, the three RCTs failed to demonstrate a superiority
      of percutaneous PFO closure vs medical therapy, a closer look at the data seems
      to suggest a trend toward benefit. We come to the conclusion that the issue of
      optimal treatment of PFO in patients with CS is far from settled and is unlikely
      to be a "one size fits all" approach due to the heterogeneity of this condition.
      In our opinion, based on the entirety of available data, both observational and
      randomized, there is likely a role for percutaneous device closure in select
      patients with CS in whom a PFO is the likely cause of their first stroke and will
      remain a significant risk for recurrent neurologic events. The article will go on
      to review current indications for atrial septal defect (ASD) closure and will
      highlight safety, efficacy and caveats regarding this technique.

PMID- 24574107
TI  - Left ventricular restoration devices.
AB  - Left ventricular (LV) remodeling results in continuous cardiac chamber
      enlargement and contractile dysfunction, perpetuating the syndrome of heart
      failure. With current exhaustion of the neurohormonal medical paradigm, surgical
      and device-based therapies have been increasingly investigated as a way to
      restore LV chamber architecture and function. Left ventricular restoration has
      been attempted with surgical procedures, such as partial left ventriculectomy,
      surgical ventricular restoration with or without revascularization, and devices,
      such as the Acorn CorCap, the Paracor HeartNet, and the Myocor Myosplint. Whereas
      all these techniques require surgical access, with or without cardiopulmonary
      bypass, a newer ventricular partitioning device (VPD) called Parachute, can be
      delivered percutaneously through the aortic valve. Designed to achieve LV
      restoration from within the ventricle, this VPD partitions the LV by isolating
      aneurysmal from normal myocardium thereby diminishing the functioning cavity.
      This review aims to critically appraise the above methods, with particular
      attention to device-based therapies. 

PMID- 24574110
TI  - Synthesis of doubly ethyl-bridged bis(p-sulfonatocalix[4]arene) and its
      supramolecular polymerization with viologen dimer.
AB  - A water-soluble supramolecular polymer with a high degree of polymerization and
      viscosity has been constructed based on the strong host-guest interaction between
      p-sulfonatocalix[4]arenes (SC4As) and viologen. A homoditopic doubly ethyl
      bridged bis(p-sulfonatocalix[4]arene) (d-SC4A) was prepared and its binding
      behavior towards methyl viologen compared with the singly ethyl-bridged bis(p
      sulfonatocalix[4]arene) (s-SC4A) by NMR spectroscopy and isothermal titration
      calorimetry. By employing a viologen dimer (bisMV(4+)) as the homoditopic guest,
      two linear AA/BB-type supramolecular polymers, d-SC4A?bisMV(4+) and s
      SC4A?bisMV(4+), were successfully constructed. Compared with s-SC4A?bisMV(4+), d
      SC4A?bisMV(4+) shows much higher solubility and viscosity, and has also been
      characterized by viscosity, diffusion-ordered NMR spectroscopy, dynamic light
      scattering, and atomic force microscopy measurements. Furthermore, the polymer is
      responsive to electrostimulus as viologen is electroactive, which was studied by
      cyclic voltammetry. This study represents a proof-of-principle as the polymer can
      potentially be applied as a self-healing and degradable polymeric material.

PMID- 24574111
TI  - Damage-associated molecular patterns stimulate interleukin-33 expression in nasal
      polyp epithelial cells.
AB  - BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a disorder
      characterized by eosinophilic inflammation and local T-helper 2 (Th2) cytokine
      production. Innate lymphoid cells that elaborate Th2 cytokines have recently been
      characterized within nasal polyps. These cells can be activated by the epithelial
      cell-derived cytokine interleukin-33 (IL-33). The objective of this study is to
      determine whether 2 molecules associated with tissue damage (high mobility group
      box-1 [HMGB-1] and adenosine triphosphate [ATP]) elicit expression of IL-33 in
      sinonasal epithelial cells (SNECs) derived from recalcitrant CRSwNP patients.
      METHODS: Ethmoid tissue was obtained from 8 recalcitrant CRSwNP and 9 control
      subjects during endoscopic sinus surgery (ESS). Tissue was prepared for
      immunohistochemistry and for SNEC air-liquid interface culture. After exposure to
      either HMGB1 or ATP in vitro, SNECs were processed for messenger RNA (mRNA)
      extraction and immunocytochemistry. IL-33 levels were determined by real-time
      polymerase chain reaction (PCR) and by immunochemical staining with anti-IL-33
      antibody. RESULTS: Intranuclear IL-33 is normally expressed in basal epithelial
      cells, but is present in more apical cells and outside the nucleus in CRSwNP.
      Exposure of SNECs to HMGB-1 or ATP resulted in a statistically significant
      increase in IL-33 mRNA expression in SNECs derived from recalcitrant CRSwNP
      patients. This increase was reflected at the protein level by immunochemical
      staining of IL-33. CONCLUSION: Tissue damage is a nonspecific trigger of
      epithelial IL-33 production in treatment-recalcitrant polyps, which may be
      responsible for perpetuating eosinophilic inflammation in CRSwNP. This common
      pathway may help explain why multiple environmental and infectious agents have
      been implicated in CRSwNP exacerbation.

PMID- 24574113
TI  - CanSNPer: a hierarchical genotype classifier of clonal pathogens.
AB  - SUMMARY: Advances in typing methodologies have recently reformed the field of
      molecular epidemiology of pathogens. The falling cost of sequencing technologies
      is creating a deluge of whole genome sequencing data that burdens bioinformatics
      resources and tool development. In particular, single nucleotide polymorphisms in
      core genomes of pathogens are recognized as the most important markers for
      inferring genetic relationships because they are evolutionarily stable and
      amenable to high-throughput detection methods. Sequence data will provide an
      excellent opportunity to extend our understanding of infectious disease when the
      challenge of extracting knowledge from available sequence resources is met. Here,
      we present an efficient and user-friendly genotype classification pipeline,
      CanSNPer, based on an easily expandable database of predefined canonical single
      nucleotide polymorphisms. AVAILABILITY AND IMPLEMENTATION: All documentation and
      Python-based source code for the CanSNPer are freely available at
      http://github.com/adrlar/CanSNPer.

PMID- 24574112
TI  - Incorporating post-translational modifications and unnatural amino acids into
      high-throughput modeling of protein structures.
AB  - MOTIVATION: Accurately predicting protein side-chain conformations is an
      important subproblem of the broader protein structure prediction problem. Several
      methods exist for generating fairly accurate models for moderate-size proteins in
      seconds or less. However, a major limitation of these methods is their inability
      to model post-translational modifications (PTMs) and unnatural amino acids. In
      natural living systems, the chemical groups added following translation are often
      critical for the function of the protein. In engineered systems, unnatural amino
      acids are incorporated into proteins to explore structure-function relationships
      and create novel proteins. RESULTS: We present a new version of SIDEpro to
      predict the side chains of proteins containing non-standard amino acids,
      including 15 of the most frequently observed PTMs in the Protein Data Bank and
      all types of phosphorylation. SIDEpro uses energy functions that are
      parameterized by neural networks trained from available data. For PTMs, the
      [Formula: see text] and [Formula: see text] accuracies are comparable with those
      obtained for the precursor amino acid, and so are the RMSD values for the atoms
      shared with the precursor amino acid. In addition, SIDEpro can accommodate any
      PTM or unnatural amino acid, thus providing a flexible prediction system for high
      throughput modeling of proteins beyond the standard amino acids. AVAILABILITY AND
      IMPLEMENTATION: SIDEpro programs and Web server, rotamer libraries and data are
      available through the SCRATCH suite of protein structure predictors at
      http://scratch.proteomics.ics.uci.edu/

PMID- 24574115
TI  - BioPlat: a software for human cancer biomarker discovery.
AB  - SUMMARY: Development of effective tools such as oligo-microarrays and next
      generation sequencing methods for monitoring gene expression on a large scale has
      resulted in the discovery of gene signatures with prognostic/predictive value in
      various malignant neoplastic diseases. However, with the exponential growth of
      gene expression databases, biologists are faced with the challenge of extracting
      useful information from these repositories. Here, we present a software package,
      BioPlat (Biomarkers Platform), which allows biologists to identify novel
      prognostic and predictive cancer biomarkers based on the data mining of gene
      expression signatures and gene expression profiling databases. BioPlat has been
      designed as an easy-to-use and flexible desktop software application, which
      provides a set of analytical tools related to data extraction, preprocessing,
      filtering, gene expression signature calculation, in silico validation, feature
      selection and annotation that leverage the integration and reuse of gene
      expression signatures in the context of follow-up data. AVAILABILITY AND
      IMPLEMENTATION: BioPlat is a platform-independent software implemented in Java
      and supported on GNU/Linux and MS Windows, which is freely available for download
      at http://www.cancergenomics.net.

PMID- 24574116
TI  - MGDB: crossing the marker genes of a user microarray with a database of public
      microarrays marker genes.
AB  - SUMMARY: The microarrays performed by scientific teams grow exponentially. These
      microarray data could be useful for researchers around the world, but
      unfortunately they are underused. To fully exploit these data, it is necessary
      (i) to extract these data from a repository of the high-throughput gene
      expression data like Gene Expression Omnibus (GEO) and (ii) to make the data from
      different microarrays comparable with tools easy to use for scientists. We have
      developed these two solutions in our server, implementing a database of
      microarray marker genes (Marker Genes Data Base). This database contains the
      marker genes of all GEO microarray datasets and it is updated monthly with the
      new microarrays from GEO. Thus, researchers can see whether the marker genes of
      their microarray are marker genes in other microarrays in the database, expanding
      the analysis of their microarray to the rest of the public microarrays. This
      solution helps not only to corroborate the conclusions regarding a researcher's
      microarray but also to identify the phenotype of different subsets of individuals
      under investigation, to frame the results with microarray experiments from other
      species, pathologies or tissues, to search for drugs that promote the transition
      between the studied phenotypes, to detect undesirable side effects of the
      treatment applied, etc. Thus, the researcher can quickly add relevant information
      to his/her studies from all of the previous analyses performed in other studies
      as long as they have been deposited in public repositories. AVAILABILITY: Marker
      gene database tool: http://ibb.uab.es/mgdb

PMID- 24574114
TI  - Optimization of gene set annotations via entropy minimization over variable
      clusters (EMVC).
AB  - MOTIVATION: Gene set enrichment has become a critical tool for interpreting the
      results of high-throughput genomic experiments. Inconsistent annotation quality
      and lack of annotation specificity, however, limit the statistical power of
      enrichment methods and make it difficult to replicate enrichment results across
      biologically similar datasets. RESULTS: We propose a novel algorithm for
      optimizing gene set annotations to best match the structure of specific empirical
      data sources. Our proposed method, entropy minimization over variable clusters
      (EMVC), filters the annotations for each gene set to minimize a measure of
      entropy across disjoint gene clusters computed for a range of cluster sizes over
      multiple bootstrap resampled datasets. As shown using simulated gene sets with
      simulated data and Molecular Signatures Database collections with microarray gene
      expression data, the EMVC algorithm accurately filters annotations unrelated to
      the experimental outcome resulting in increased gene set enrichment power and
      better replication of enrichment results. AVAILABILITY AND IMPLEMENTATION:
      http://cran.r-project.org/web/packages/EMVC/index.html.

PMID- 24574117
TI  - Deciphering kinase-substrate relationships by analysis of domain-specific
      phosphorylation network.
AB  - MOTIVATION: In silico prediction of site-specific kinase-substrate relationships
      (ssKSRs) is crucial for deciphering phosphorylation networks by linking kinomes
      to phosphoproteomes. However, currently available predictors for ssKSRs give rise
      to a large number of false-positive results because they use only a short
      sequence stretch around phosphosite as determinants of kinase specificity and do
      not consider the biological context of kinase-substrate recognition. RESULTS:
      Based on the analysis of domain-specific kinase-substrate relationships, we have
      constructed a domain-level phosphorylation network that implicitly incorporates
      various contextual factors. It reveals preferential phosphorylation of specific
      domains by certain kinases. These novel correlations have been implemented in
      PhosNetConstruct, an automated program for predicting target kinases for a
      substrate protein. PhosNetConstruct distinguishes cognate kinase-substrate pairs
      from a large number of non-cognate combinations. Benchmarking on independent
      datasets using various statistical measures demonstrates the superior performance
      of PhosNetConstruct over ssKSR-based predictors. AVAILABILITY AND IMPLEMENTATION:
      PhosNetConstruct is freely available at
      http://www.nii.ac.in/phosnetconstruct.html.

PMID- 24574118
TI  - Canto: an online tool for community literature curation.
AB  - MOTIVATION: Detailed curation of published molecular data is essential for any
      model organism database. Community curation enables researchers to contribute
      data from their papers directly to databases, supplementing the activity of
      professional curators and improving coverage of a growing body of literature. We
      have developed Canto, a web-based tool that provides an intuitive curation
      interface for both curators and researchers, to support community curation in the
      fission yeast database, PomBase. Canto supports curation using OBO ontologies,
      and can be easily configured for use with any species. AVAILABILITY: Canto code
      and documentation are available under an Open Source license from
      http://curation.pombase.org/. Canto is a component of the Generic Model Organism
      Database (GMOD) project (http://www.gmod.org/).

PMID- 24574121
TI  - Measured resection versus gap balancing for total knee arthroplasty.

PMID- 24574120
TI  - Proximal tumor location and fluid-fluid levels on MRI predict resistance to
      chemotherapy in stage IIB osteosarcoma.
AB  - BACKGROUND: Primary tumor growth during neoadjuvant chemotherapy is believed to
      be a sign of resistance to chemotherapy (chemoresistance), and often is
      associated with poor histologic response, local recurrence, and poorer survival.
      Currently there are no proven indicators to predict poor response to chemotherapy
      at the time of diagnosis. QUESTIONS/PURPOSES: We asked (1) what clinicopathologic
      factors present at diagnosis predict primary tumor growth during neoadjuvant
      chemotherapy, (2) what factors at presentation predict survival, and (3) when the
      factors at presentation and the treatment-related factors are considered, what
      factors independently correlate with survival. METHODS: We studied 567 patients
      with Stage IIB osteosarcomas. The factors assessed included age, sex, location,
      pattern on plain radiographs (radiodense, radiolucent, mixed), MRI findings,
      pathologic subtype, initial tumor volume determined by MRI, tumor volume change
      after chemotherapy, surgical margin, and histologic response to preoperative
      chemotherapy. Logistic modeling was used to identify risk factors. RESULTS:
      Independent risk factors associated with primary tumor growth after neoadjuvant
      chemotherapy were proximal tumor location (p < 0.01; relative risk [RR], 2.41;
      95% CI, 1.5-3.86) and fluid-fluid level on initial MRI (p < 0.01; RR, 5.56; 95%
      CI, 3.48-8.87). Among factors at presentation, large initial tumor volume (p <
      0.01; RR, 1.58; 95% CI, 1.22-2.04), proximal tumor site (p < 0.01; RR, 1.61; 95%
      CI, 1.19-2.19), and presence of fluid-fluid level (p < 0.01; RR, 1.83; 95% CI,
      1.37-2.5) independently predicted reduced event-free survival. When we consider
      the factors at presentation and treatment-related factors, large initial tumor
      volume (p < 0.01; RR, 1.54), tumor growth after neoadjuvant chemotherapy (p <
      0.01; RR, 3.88), inadequate surgical margin (p < 0.01; RR, 2.42), and poor
      histologic response (p = 0.03; RR, 1.43) were independent poor prognostic factors
      of event-free survival. CONCLUSIONS: Proximal tumor location and the presence of
      the fluid-fluid level on initial MRI were predictors of tumor progression and
      poor survival in patients presenting with Stage IIB osteosarcomas. If confirmed
      in other studies, patients with these risk factors should be considered for
      trials of other treatment strategy. LEVEL OF EVIDENCE: Level III, prognostic
      study. See the Instructions for Authors for a complete description of levels of
      evidence.

PMID- 24574123
TI  - Obituary: A remembrance: Henry Alexander Yancey Jr. MD (1933-2013).

PMID- 24574122
TI  - Psychologic distress reduces preoperative self-assessment scores in
      femoroacetabular impingement patients.
AB  - BACKGROUND: In several areas of orthopaedics, including spine and upper extremity
      surgery, patients with greater levels of psychologic distress report worse self
      assessments of pain and function than patients who are not distressed. This
      effect can lead to lower than expected baseline scores on common patient-reported
      outcome scales, even those not traditionally considered to have a psychologic
      component. QUESTIONS/PURPOSES: The purposes of this study were to determine (1)
      the association of psychologic distress and baseline modified Harris hip scores
      and Hip Outcome Scores in patients undergoing hip arthroscopy; and (2) whether
      psychologic distress would remain a significant negative predictor of baseline
      hip scores when other clinical variables such as age, sex, BMI, smoking status,
      and American Society of Anesthesiologists (ASA) classification were controlled.
      METHODS: One hundred forty-seven patients at one center were prospectively
      enrolled when they scheduled hip arthroscopy to treat painful femoroacetabular
      impingement. Before surgery, psychologic distress was quantified using the
      Distress Risk Assessment Method questionnaire. Patients also completed baseline
      self-assessments of hip pain and function including the modified Harris hip score
      and the Hip Outcome Score. Age, sex, BMI, smoking status, and ASA classification
      were recorded for each patient. Bivariate correlations and multivariate
      regression models were used to assess the effect of psychologic distress on
      patient self-assessment of hip pain and function. RESULTS: Patients with distress
      reported significantly lower baseline modified Harris hip scores (58 versus 67, p
      = 0.001), Hip Outcome Score-Activities of Daily Living scores (62 versus 72, p =
      0.002), and Hip Outcome Score-Sports scores (36 versus 47, p = 0.02). Distress
      remained significantly associated with lower baseline modified Harris hip (p =
      0.006), Hip Outcome Score-Activities of Daily Living (p = 0.005), and Hip Outcome
      Score-Sports scores (p = 0.017) when age, sex, BMI, smoking status, and ASA
      classification were controlled for in the multivariate model. CONCLUSIONS:
      Practitioners should recognize that psychologic distress has a negative
      correlation with baseline patient self-assessment using the modified Harris hip
      score and the Hip Outcome Scores, scales not previously described to correlate
      with psychologic distress. Longitudinal followup is warranted to clarify the
      relationship between distress and self-perceived disability and the effect of
      distress on postoperative outcomes in patients having hip arthroscopy. LEVEL OF
      EVIDENCE: Level III, prognostic study. See the Instructions for Authors for a
      complete description of levels of evidence.

PMID- 24574124
TI  - Is peroneal nerve injury associated with worse function after knee dislocation?
AB  - BACKGROUND: Peroneal nerve palsy is a frequent and potentially disabling
      complication of multiligament knee dislocation, but little information exists on
      the degree to which patients recover motor or sensory function after this injury,
      and whether having this nerve injury--with or without complete recovery--is a
      predictor of inferior patient-reported outcome scores. QUESTIONS/PURPOSES: The
      purposes of this study were to (1) report on motor and sensory recovery as well
      as patient-reported outcomes scores of patients with peroneal nerve injury from
      multiligament knee dislocation; (2) compare those endpoints between patients who
      had partial versus complete nerve injuries; and (3) compare patient-reported
      outcomes among patients who sustained peroneal nerve injuries after knee
      dislocation with a matched cohort of multiligament knee injuries without nerve
      injury. METHODS: Thirty-two patients were identified, but five did not have 2
      year followup and are excluded (16% lost to followup). Twenty-seven patients (24
      male, three female) with peroneal nerve injury underwent multiligament knee
      reconstruction and were followed for 6.3 years (range, 2-18 years). Motor grades
      were assessed by examination and outcomes by International Knee Documentation
      Committee (IKDC) and Lysholm scores. Retrospectively, patients were divided into
      complete (n = 9) and partial nerve palsy (n = 18). Treatment for complete nerve
      palsy included an ankle-foot orthosis for all patients, nonoperative (one),
      neurolysis (two), tendon transfer (three), nerve transfer (one), and combined
      nerve/tendon transfer (one). Treatment for partial nerve palsy included
      nonoperative (12), neurolysis (four), nerve transfer (one), and combined
      nerve/tendon transfer (one). Furthermore, patients without nerve injury were
      matched by Schenck classification, age, and sex. Data were analyzed using
      univariate and multivariate models. RESULTS: Overall, 18 patients (69%) regained
      antigravity ankle dorsiflexion after treatment (three complete nerve palsy [38%]
      versus 15 partial nerve palsy [83%]; p = 0.06). One patient with complete nerve
      palsy (13%) and 13 patients with partial nerve palsy (72%) regained antigravity
      extensor hallucis longus strength (p = 0.01). IKDC and Lysholm scores were
      similar between complete nerve palsy and partial nerve palsy groups. After
      controlling for confounding variables such as patient age, body mass index,
      injury interval to surgery, mechanism of injury, bicruciate injury, and popliteal
      artery injury status, there was no difference between patients with peroneal
      nerve injury and those without on Lysholm or IKDC scores. CONCLUSIONS: With
      multiligament knee dislocation and associated peroneal nerve injury, patients
      with partial nerve injury are more likely to regain antigravity strength when
      compared with those with a complete nerve injury, but their overall function may
      not improve. After controlling for confounding variables in a multivariate model,
      there was no difference in Lysholm or IKDC scores between patients with peroneal
      nerve injury and those without. LEVEL OF EVIDENCE: Level III, therapeutic study.
      See Guidelines for Authors for a complete description of levels of evidence.

PMID- 24574125
TI  - A pilot study of the effects of intranasal budesonide delivered by NasoNeb(r) on
      patients with perennial allergic rhinitis.
AB  - BACKGROUND: We investigated whether nebulization of budesonide via a NasoNeb(r)
      device would treat perennial allergic rhinitis. METHODS: We performed a parallel,
      randomized, double-blind, placebo-controlled, pilot study in subjects (n = 40)
      with perennial allergic rhinitis. After recording baseline symptoms, subjects
      were randomized to budesonide respules (0.25 mg) or an equivalent placebo for 26
      days. Nasal peak inspiratory flow (NPIF) and nasal symptoms (graded on a 0-3
      scale) were recorded by the subjects twice daily. Rhinoconjunctivitis quality of
      life (RQOL) as well as nasal volume, measured by acoustic rhinometry, was
      obtained at baseline, after 2 weeks, and at the end of treatment. RESULTS: The
      average change from baseline in symptoms over the treatment period was greater
      for the group on budesonide (-3.33) compared to placebo (-1.98) (p = 0.45). When
      the average change from baseline over the treatment period was compared between
      the groups, budesonide resulted in higher NPIF (36.4 L/min) than placebo (18.7
      L/min), p = 0.094. QOL improved in both groups compared to baseline with no
      significant difference between the groups. Although acoustic rhinometry indicated
      a larger volume in the group treated with budesonide on the last trial visit, the
      differences between the groups were not significant when accounting for the
      baseline values. CONCLUSION: Compared to placebo, administration of nebulized
      budesonide in subjects with perennial allergic rhinitis resulted in improvements
      in symptoms and objective measures of nasal congestion which approached but did
      not achieve statistical significance. A higher dose of active agent, a less
      effective placebo and a larger number of subjects might have improved statistical
      significance.

PMID- 24574126
TI  - Oxonium ions substituting cesium ions in the structure of the new high-pressure
      borate HP-Cs(1-x)(H(3)O)(x)B(3)O(5) (x=0.5-0.7).
AB  - The new high-pressure borate HP-Cs1-x (H3 O)x B3 O5 (x=0.5-0.7) was synthesized
      under high-pressure/high-temperature conditions of 6 GPa/900  degrees C in a
      Walker-type multianvil apparatus. The compound crystallizes in the monoclinic
      space group C2/c (Z=8) with the parameters a=1000.6(2), b=887.8(2), c=926.3(2)
      pm, beta=103.1(1) degrees , V=0.8016(3) nm(3) , R1=0.0452, and wR2=0.0721 (all
      data). The boron-oxygen network is analogous to those of the compounds HP-MB3 O5
      , (M=K, Rb) and exhibits all three structural motifs of borates-BO3 groups,
      corner-sharing BO4 tetrahedra, and edge-sharing BO4 tetrahedra-at the same time.
      Channels inside the boron-oxygen framework contain the cesium and oxonium ions,
      which are disordered on a specific site. Estimating the amount of hydrogen by
      solid-state NMR spectroscopy and X-ray diffraction led to the composition HP-Cs1
      x (H3 O)x B3 O5 (x=0.5-0.7), which implies a nonzero phase width. 

PMID- 24574127
TI  - Governing by "gotcha".

PMID- 24574128
TI  - Monitoring health reform efforts: which state-level data to use?
AB  - This study compares estimates of health insurance coverage from the American
      Community Survey (ACS) to those in twelve state-specific surveys. Uninsurance
      estimates for the nonelderly are consistently higher in the ACS than in state
      surveys, as are direct purchase insurance estimates. Estimates for employer
      sponsored insurance are similar, but public coverage rates are lower in the ACS.
      The ACS meets some but not all of the states' data needs; its large sample size
      and inclusion of all U.S. counties in the sample allow for comparison of
      insurance coverage within and across states. State-specific surveys provide the
      flexibility to add policy-relevant questions, including questions needed to
      examine how health insurance translates into access, use, and affordability of
      health services.

PMID- 24574129
TI  - Preparing to measure health coverage in federal surveys post-reform: lessons from
      Massachusetts.
AB  - In preparation for health reform in 2014, qualitative research was conducted with
      Massachusetts residents to explore how to adapt surveys to accommodate reporting
      information about health exchanges. Questions about exchange participation were
      effective when state-specific exchange program names were offered, but generic
      terms such as "marketplace" and "exchange" did not resonate with respondents.
      However, respondents were able to understand new questions about premiums and
      subsidies and to answer with a high degree of accuracy. These questions, taken in
      tandem with answers on plan type, were sufficient to distinguish among Medicaid,
      subsidized exchange coverage, and unsubsidized coverage, even without the benefit
      of state-specific exchange program names.

PMID- 24574130
TI  - The capacity of the Medical Expenditure Panel Survey to inform the Affordable
      Care Act.
AB  - The Affordable Care Act (ACA) was enacted with major provisions to expand health
      insurance coverage, control health care costs, and improve the health care
      delivery system. Essential data resources will be required for effective program
      planning, administration, and management, in addition to facilitating evaluations
      of program performance. The Medical Expenditure Panel Survey (MEPS) is one of the
      core data resources that has been used to inform several provisions of the ACA.
      This paper provides a summary of the capacity of the MEPS to inform program
      planning, implementation, and evaluations of program performance for several
      components of the ACA. 

PMID- 24574131
TI  - The expansion of Medicaid coverage under the ACA: implications for health care
      access, use, and spending for vulnerable low-income adults.
AB  - The expansion of Medicaid coverage under the Affordable Care Act offers the
      potential for significant increases in health care access, use, and spending for
      vulnerable nonelderly adults who are uninsured. Using pooled data from the
      Medical Expenditure Panel Survey, this study estimates the potential effects of
      Medicaid, controlling for individual and local community characteristics. Our
      findings project significant gains in health care access and use for uninsured
      adults who enroll in Medicaid coverage and have chronic health conditions and
      mental health conditions. With that increased use, annual per capita health care
      spending for those newly insured individuals (excluding out-of-pocket spending)
      is projected to grow from $2,677 to $6,370 in 2013 dollars, while their out-of
      pocket spending would drop by $921. It is expected that these increases in
      spending would be offset at least in part by reductions in uncompensated care and
      charity care. 

PMID- 24574132
TI  - Do workplace wellness programs reduce medical costs? Evidence from a Fortune 500
      company.
AB  - The recent passage of the Affordable Care Act has heightened the importance of
      workplace wellness programs. This paper used administrative data from 2002 to
      2007 for PepsiCo's self-insured plan members to evaluate the effect of its
      wellness program on medical costs and utilization. We used propensity score
      matching to identify a comparison group who were eligible for the program but did
      not participate. No significant changes were observed in inpatient admissions,
      emergency room visits, or per-member per-month (PMPM) costs. The discrepancy
      between our findings and those of prior studies may be due to the difference in
      intervention intensity or program implementation.

PMID- 24574136
TI  - Borderline personality pathology and insomnia symptoms in community-dwelling
      older adults.
AB  - Prior research has associated BPD with sleep problems, but the relationship has
      been explored primarily in small clinical samples of younger adults. Findings
      from our lab have demonstrated that borderline symptoms remain present in later
      middle age and are associated with several negative life outcomes. A
      representative community sample of older adults (N = 633, Mage  = 62.3) was
      obtained from the St Louis area, and interviewer-reports, self-reports, and
      informant-reports of personality pathology were completed along with an insomnia
      symptoms questionnaire. Cross-sectional analyses revealed that symptoms from all
      10 DSM-IV personality disorders were significantly correlated with insomnia
      symptoms. However, after statistically controlling for major depression, body
      mass index, race and gender, only borderline personality pathology remained
      significantly associated with insomnia symptoms. Our results demonstrate that in
      addition to other negative health outcomes, borderline personality pathology is
      uniquely associated with sleep problems in later middle-aged adults in the
      community.

PMID- 24574137
TI  - From mechanical stimulation to biological pathways in the regulation of stem cell
      fate.
AB  - Mechanical stimuli are important in directing the fate of stem cells; the effects
      of mechanical stimuli reported in recent research are reviewed here. Stem cells
      normally undergo two fundamental processes: proliferation, in which their numbers
      multiply, and differentiation, in which they transform into the specialized cells
      needed by the adult organism. Mechanical stimuli are well known to affect both
      processes of proliferation and differentiation, although the complete pathways
      relating specific mechanical stimuli to stem cell fate remain to be elucidated.
      We identified two broad classes of research findings and organized them according
      to the type of mechanical stress (compressive, tensile or shear) of the stimulus.
      Firstly, mechanical stress of any type activates stretch-activated channels
      (SACs) on the cell membrane. Activation of SACs leads to cytoskeletal remodelling
      and to the expression of genes that regulate the basic growth, survival or
      apoptosis of the cells and thus regulates proliferation. Secondly, mechanical
      stress on cells that are physically attached to an extracellular matrix (ECM)
      initiates remodelling of cell membrane structures called integrins. This second
      process is highly dependent on the type of mechanical stress applied and result
      into various biological responses. A further process, the Wnt pathway, is also
      implicated: crosstalk between the integrin and Wnt pathways regulates the switch
      from proliferation to differentiation and finally regulates the type of
      differentiation. Therefore, the stem cell differentiation process involves
      different signalling molecules and their pathways and most likely depends upon
      the applied mechanical stimulation.

PMID- 24574138
TI  - Arteriovenous fistula stenosis in hemodialysis patients is characterized by an
      increased adventitial fibrosis.
AB  - BACKGROUND: Arteriovenous fistula (AVF) stenosis is the major cause of vascular
      access failure in hemodialysis. Adventitial remodeling has been suggested to play
      a role in the pathogenesis of AVF stenosis. This study aimed to evaluate
      adventitial fibrosis in stenotic AVF and investigate the underlying molecular
      mechanisms. METHODS: Forty-four patients undergoing surgery for AVF creation were
      examined; ten presented AVF failure, with histological-proven AVF stenosis.
      RESULTS: In stenotic AVF we observed a significant increase of adventitia
      extracellular matrix deposition and alpha-smooth muscle actin (alpha-SMA)(+) cell
      numbers; most of these cells were myofibroblast (alpha-SMA(+)/vimentin(+)).
      Phosphorylated platelet-derived growth factor beta receptor (p-PDGFRbeta) was
      significantly increased within the adventitia of stenotic compared to native AVF,
      along with a marked increase in the phosphorylation of Akt and ERK, two key
      kinases in PDGFRbeta signalling. Myofibroblasts were the main cell type
      associated with the activation of p-PDGFRbeta. At the same time, we observed a
      significant adventitial vessels rarefaction in stenotic AVF, as demonstrated by a
      reduced CD34 expression. This event was associated with a marked reduction in the
      expression of KDR/fetal liver kinase-1, the main vascular endothelial growth
      factor receptor. The degree of adventitial fibrosis was directly correlated with
      the extent of adventitial alpha-SMA and inversely associated with adventitial
      CD34 expression. Finally, we observed an increase in CD34(+)/alpha-SMA(+) cells
      within the adventitia of failed AVF. CONCLUSION: This study suggests that AVF
      failure is associated with an increased adventitial fibrosis, myofibroblast
      activation and capillary rarefaction, potentially linked with endothelial-to
      mesenchymal transition. In this scenario, our data suggest that PDGF may play a
      pathogenic role.

PMID- 24574139
TI  - Local ZnCl2 accelerates fracture healing.
AB  - This study evaluated the effect of local zinc chloride (ZnCl2 ), an insulin
      mimetic agent, upon the early and late parameters of fracture healing in rats
      using a standard femur fracture model. Mechanical testing, radiographic scoring,
      histomorphometry, qualitative histological scoring, PCNA immunohistochemistry,
      and local growth factor analysis were performed. Fractures treated with local
      ZnCl2 possessed significantly increased mechanical properties compared to
      controls at 4 weeks post fracture. The radiographic scoring analysis showed
      increased cortical bridging at 4 weeks in the 1.0 (p=0.0015) and 3.0 (p<0.0001)
      mg/kg ZnCl2 treated groups. Histomorphometry of the fracture callus at day 7
      showed 177% increase (p=0.036) in percent cartilage and 133% increase (p=0.002)
      in percent mineralized tissue with local ZnCl2 treatment compared to controls.
      Qualitative histological scoring showed a 2.1* higher value at day 7 in the ZnCl2
      treated group compared to control (p = 0.004). Cell proliferation and growth
      factors, VEGF and IGF-I, within fracture calluses treated with local ZnCl2 were
      increased at day 7. The results suggest local administration of ZnCl2 increases
      cell proliferation, causing increased growth factor production which yields
      improved chondrogenesis and endochondral ossification. Ultimately, these events
      lead to accelerated fracture healing as early as 4 weeks post fracture.

PMID- 24574142
TI  - Simultaneous functional MRI acquisition of distributed brain regions with high
      temporal resolution using a 2D-selective radiofrequency excitation.
AB  - PURPOSE: To perform simultaneous functional MRI of multiple, distributed brain
      regions at high temporal resolution using a 2D-selective radiofrequency (2DRF)
      excitation. METHODS: A tailored 2DRF excitation is used to excite several, small
      regions-of-interest distributed in the brain. They are acquired in a single
      projection image with an appropriately chosen orientation such that the different
      regions-of-interest can be discriminated by their position in the projection
      plane. Thus, they are excited and acquired simultaneously with a temporal
      resolution comparable to that of a single-slice measurement. The feasibility of
      this approach for functional neuroimaging (in-plane resolution 2 * 2 mm(2) ) at
      high temporal resolution (80 ms) is demonstrated in healthy volunteers for
      regions-of-interest in the visual and motor system using checkerboard and finger
      tapping block-design paradigms. RESULTS: Task-related brain activation could be
      observed in both the visual and the motor system simultaneously with a high
      temporal resolution. For an onset shift of 240 ms for half of the checkerboard, a
      delay of the hemodynamic response in the corresponding hemisphere of the visual
      cortex could be detected. CONCLUSION: Limiting the excited magnetization to the
      desired target regions with a 2DRF excitation reduces the imaging sampling
      requirements which can improve the temporal resolution significantly.

PMID- 24574140
TI  - Dentin biomodification potential depends on polyphenol source.
AB  - Although proanthocyanidins (PACs) modify dentin, the effectiveness of different
      PAC sources and the correlation with their specific chemical composition are
      still unknown. This study describes the chemical profiling of natural PAC-rich
      extracts from 7 plants using ultra high pressure/performance liquid
      chromatography (UHPLC) to determine the overall composition of these extracts
      and, in parallel, comprehensively evaluate their effect on dentin properties. The
      total polyphenol content of the extracts was determined (as gallic acid
      equivalents) using Folin-Ciocalteau assays. Dentin biomodification was assessed
      by the modulus of elasticity, mass change, and resistance to enzymatic
      biodegradation. Extracts with a high polyphenol and PAC content from Vitis
      vinifera, Theobroma cacao, Camellia sinensis, and Pinus massoniana induced a
      significant increase in modulus of elasticity and mass. The UHPLC analysis showed
      the presence of multiple types of polyphenols, ranging from simple phenolic acids
      to oligomeric PACs and highly condensed tannins. Protective effect against
      enzymatic degradation was observed for all experimental groups; however,
      statistically significant differences were observed between plant extracts. The
      findings provide clear evidence that the dentin bioactivities of PACs are source
      dependent, resulting from a combination of concentration and specific chemical
      constitution of the complex PAC mixtures. 

PMID- 24574143
TI  - Complete 1H NMR assignments of pyrrolizidine alkaloids and a new eudesmanoid from
      Senecio polypodioides.
AB  - Chemical investigation of the aerial parts of Senecio polypodioides lead to the
      isolation of the new eudesmanoid 1beta-angeloyloxyeudesm-7-ene-4beta,9alpha-diol
      (1) and the known dirhamnosyl flavonoid lespidin (3), while from roots, the known
      7beta-angeloyloxy-1-methylene-8alpha-pyrrolizidine (5) and sarracine N-oxide (6),
      as well as the new neosarracine N-oxide (8), were obtained. The structure of 1
      and 8 was elucidated by spectral means. Complete assignments of the (1)H NMR data
      for 5, 6, sarracine (7), and 8 were made using one-dimensional and two
      dimensional NMR experiments and by application of the iterative full spin
      analysis of the PERCH NMR software.

PMID- 24574144
TI  - Controlled carbon nitride growth on surfaces for hydrogen evolution electrodes.
AB  - Efficient and low-cost electrocatalysts for the hydrogen evolution reaction are
      highly desired for future renewable energy systems. Described herein is the
      reduction of water to hydrogen using a metal-free carbon nitride electrocatalyst
      which operates in neutral and alkaline environments. An efficient, easy, and
      general method for growing ordered carbon nitride on different electrodes was
      developed. The metal-free catalyst demonstrates low overpotential values, which
      are comparable to those of non-noble metals, with reasonable current densities.
      The facile deposition method enables the fabrication of many electronic and
      photoelectronic devices based on carbon nitride for renewable energy
      applications. 

PMID- 24574145
TI  - Direct synthetic route to functionalized 1,2-azaborinines.
AB  - A new catalytic synthetic route to functionalized 1,2-azaborinines has been
      developed by the [2+2]/[2+4] cycloaddition reactions of di-tert-butyliminoboranes
      and alkynes in presence of a rhodium catalyst. The first examples of ferrocene
      functionalized azaborinines have been synthesized using this strategy. Moreover,
      the regioselectivity of this reaction can be controlled by the formation of an
      intermediate rhodium 1,2-azaborete complex, which results in the isolation of the
      first azaborinine boronic ester. The isolation of an NH-containing BN isostere by
      elimination of isobutene from an N(tBu) group under thermolytic conditions has
      also been achieved. Theoretical studies give further insight into the formation
      of 1,2-azaborinines and the elimination of isobutene from the N(tBu) group. 

PMID- 24574146
TI  - Effect of mobile phase composition on the liquid chromatographic
      enantioseparation of bulky monoterpene-based beta-amino acids by applying chiral
      stationary phases based on Cinchona alkaloid.
AB  - Stereoselective HPLC separations of five sterically constrained monoterpene-based
      2-aminocarboxylic acid enantiomers were carried out by using the newly developed
      zwitterionic chiral stationary phases Chiralpak ZWIX(+)TM and ZWIX(-)TM based on
      Cinchona alkaloid. In order to optimize the retention and enantioselectivity
      parameters, the ratio of the different organic solvents in the mobile phase and
      the nature of the acid and base additives (counter- and co-ions) were
      systematically varied. The effects of structure variants of the analytes on the
      resolution were investigated. The elution sequence was determined in all cases
      and observed to be opposite on ZWIX(+)TM and ZWIX(-)TM. 

PMID- 24574148
TI  - Detection of feline Mycoplasma species in cats with feline asthma and chronic
      bronchitis.
AB  - Little is known about the aetiology of inflammatory lower airway disease in cats.
      The aim of this study was to investigate the role of Mycoplasma species in cats
      with feline asthma (FA) and chronic bronchitis (CB). The study population
      consisted of 17 cats with FA/CB, and 14 sick cats without clinical and historical
      signs of respiratory disease, which were euthanased for various other reasons.
      Nasal swabs, nasal lavage and bronchoalveolar lavage fluid (BALF) samples were
      taken from patients from both groups. Mycoplasma species culture with modified
      Hayflick agar and Mycoplasma polymerase chain reaction (PCR) were performed on
      all samples followed by sequencing of all Mycoplasma species-positive samples for
      differentiation of subspecies. PCR testing detected significantly more Mycoplasma
      species-positive BALF samples than Mycoplasma culture (P = 0.021). When cats with
      oropharyngeal contamination were excluded from comparison, the numbers of
      Mycoplasma species-positive BALF samples in the group with FA/CB (6/17) and the
      control group (4/9) were not significantly different (P = 0.6924). While all
      nasal samples of the cats with FA/CB were negative for Mycoplasma organisms, five
      samples in the control group (P = 0.041) were positive on PCR. Sequencing
      revealed Mycoplasma felis in all PCR-positive samples. Mycoplasma species can be
      detected in the lower airways of cats with FA/CB, as well as in the BALF of sick
      cats without respiratory signs. Further studies are warranted to investigate the
      possibility that Mycoplasma species represent commensals of the lower respiratory
      tract of cats. 

PMID- 24574149
TI  - Simultaneous determination of aliskiren hemifumarate, amlodipine besylate, and
      hydrochlorothiazide in their triple mixture dosage form by capillary zone
      electrophoresis.
AB  - A novel, specific, reliable, and accurate capillary zone electrophoretic method
      was developed and validated for the simultaneous determination of aliskiren
      hemifumarate, amlodipine besylate, and hydrochlorothiazide in their triple
      mixture dosage form. Separation was carried out in a fused-silica capillary (57.0
      cm total length and 50.0 cm effective length, 75.6 MUm internal diameter) by
      applying a potential of 17 kV and a running buffer consisting of 40 mM phosphate
      buffer at pH 6.0 with UV detection at 245 nm. The method was suitably validated
      with respect to specificity, linearity, LOD, and LOQ, accuracy, precision, and
      robustness. The method showed good linearity in the ranges 1-10, 2.5-25, and 30
      300 MUg/mL with LODs of 0.11, 0.33, and 5.83 MUg/mL for amlodipine besylate,
      hydrochlorothiazide, and aliskiren hemifumarate, respectively. The proposed
      method was successfully applied for the analysis of the studied drugs in their
      coformulated tablets. The results of the proposed method were statistically
      compared with those obtained by the RP-HPLC reference method revealing no
      significant differences in the performance of the methods regarding accuracy and
      precision.

PMID- 24574147
TI  - The role of biomarkers in the assessment of aquatic ecosystem health.
AB  - Ensuring the health of aquatic ecosystems and identifying species at risk from
      the detrimental effects of environmental contaminants can be facilitated by
      integrating analytical chemical analysis with carefully selected biological
      endpoints measured in tissues of species of concern. These biological endpoints
      include molecular, biochemical, and physiological markers (i.e., biomarkers) that
      when integrated, can clarify issues of contaminant bioavailability,
      bioaccumulation, and ecological effects while enabling a better understanding of
      the effects of nonchemical stressors. In the case of contaminant stressors, an
      understanding of chemical modes of toxicity can be incorporated with diagnostic
      markers of aquatic animal physiology to help understand the health status of
      aquatic organisms in the field. Furthermore, new approaches in functional
      genomics and bioinformatics can help discriminate individual chemicals, or groups
      of chemicals among complex mixtures that may contribute to adverse biological
      effects. Although the use of biomarkers is not a new paradigm, such approaches
      have been underused in the context of ecological risk assessment and natural
      resource damage assessment. From a regulatory standpoint, these approaches can
      help better assess the complex effects from coastal development activities to
      assessing ecosystem integrity pre- and post development or site remediation.

PMID- 24574150
TI  - Docetaxel epimerization in silicone films: a case of drug excipient
      incompatibility.
AB  - Docetaxel (DTX) is an anti-cancer compound derived from 10-deacetyl baccatin III
      which is indicated for treatment of breast, lung, prostate, gastro-esophageal,
      and head and neck cancers. Epimerization of DTX at the C-7 hydroxyl position has
      intrigued chemists and has been implicated in loss of potency, as well as in the
      development of resistance in tumour cells. For localized controlled delivery of
      this agent, silicone films were prepared from a commercially available silicone
      kit. High levels of epimeric degradants were unexpectedly found in the in vitro
      release media. Herein, we discuss this anomalous DTX degradation to epimeric
      impurities, and discuss the possible reasons for degradation. Systematic
      stability studies were performed on the release media and the silicone kit
      components. It was found that release media and tin-based catalyst present in the
      silicone kit could be responsible for the epimeric conversion. This unusual case
      of chemical incompatibility can affect product performance and can even lead to
      development of resistance in tumour cells towards DTX.

PMID- 24574151
TI  - Multiplexed measurements of immunomodulator levels in peripheral blood of healthy
      subjects: Effects of analytical variables based on anticoagulants, age, and
      gender.
AB  - Multiplex microbead immunoassay (MMIA) is a powerful technology for a wide range
      of biomedical and clinical applications. It is important to study the normal
      concentration ranges of immunomodulators under different sample preparation
      conditions and age groups of subjects in order to more precisely determine their
      reference values for use in assessing alterations of their levels in disease. The
      aim of this study was to determine the plasma concentrations of immunomodulators
      (cytokines, chemokines, and growth factors) in the peripheral blood from healthy
      subjects by the use of a large multiplex panel, and to determine the effects of
      different anticoagulants, age, and gender on the immunomodulator levels. In
      addition, the assay precision for these biomarker analytes was determined. Plasma
      samples from 107 healthy subjects, aged 18 to 85 years, were collected in three
      different anticoagulants (sodium citrate, EDTA, Heparin); corresponding serum
      samples were also obtained. Multiplex microbead immunoassays were performed for
      measuring a total of 23 analytes including chemokines, cytokines, and growth
      factors (IL-1beta, IL-1ra, IL-2, IL-6, IL-7, IL-8, IL-12 p70, IL-17, IFN-gamma,
      IP-10, MCP-1, PDGF-BB, RANTES, TNF-alpha, IL-1a, IL-16, HGF, MIG, TNF-beta, PDGF
      ABBB, EGF, Flt-3 Ligand, VEGF). For these analytes, our results showed that the
      anticoagulant affected the concentration measurements and the coefficients of
      variation. However, the relative levels of the analytes (profiles) of samples
      collected in a particular anticoagulant are consistent. The analytes IL-1beta, IL
      7, Flt-3 Ligand, and IL-12p70 show the largest variation (up to fourfold) between
      the age groups. In addition, no statistically significant differences in the
      level of the analytes were found between the sexes.

PMID- 24574152
TI  - Testosterone deficiency and severity of erectile dysfunction are independently
      associated with reduced quality of life in men with type 2 diabetes.
AB  - Erectile dysfunction (ED) and low testosterone levels are common in men with type
      2 diabetes (T2D). We have investigated the impact of testosterone on quality of
      life (QoL) in diabetic men with ED. Men with ED were identified within a study
      cohort of 355 men with T2D. All subjects completed SF-36 health and Androgen
      Deficiency of the Aging Male questionnaires. Total tesosterone (TT), bioavailable
      testosterone (BT) and sex hormone-binding globulin levels of study participants
      were measured and free testosterone levels were calculated (cFT). A subgroup of
      126 ED patients completed the International Index of Erectile Function-5 (IIEF-5)
      questionnaire. Linear regression analyses were corrected for age, body mass index
      (BMI), glycosylated haemoglobin (HbA1c), smoking, alcohol consumption and
      cardiovascular disease (CVD). Total SF-36 scores significantly and positively
      correlated with TT levels (r = 0.219, p = 0.001), BT levels (r = 0.199, p =
      0.004) and cFT levels (r = 0.185, p = 0.007) among men with ED. These trends were
      strengthened after adjusting for age, BMI, HbA1c, smoking, alcohol consumption
      and CVD (TT r = 0.359, p = 0.015; BT r = 0.354, p = 0.024 and cFT r = 0.354, p =
      0.024). IIEF-5 scores significantly correlated inversely with TT (r = 0.546, p =
      0.001), BT (r = 0.506, p = 0.004) and cFT levels (r = 0.532, p = 0.001). A
      positive linear relationship was observed between IIEF-5 scores and total SF-36
      score (r = 0.491, p = 0.003). Patients who reported having ED had an average SF
      36 score of 9.1% less than those without ED (p < 0.001). Lower testosterone and
      greater severity of ED independently correlated with poorer physical function,
      social function, vitality and decline in general health domains of the SF-36.
      This is the first study to report that testosterone deficiency and severity of ED
      are both independently associated with reduced QoL in men with T2D. Furthermore,
      ED and low testosterone are markers of poor health which impact on an
      individual's self-perception of their health status.

PMID- 24574154
TI  - The Swedish Version of the Breastfeeding Self-Efficacy Scale-Short Form:
      Reliability and Validity Assessment.
AB  - BACKGROUND: Among Swedish mothers, breastfeeding duration has been declining in
      recent years. An instrument for early identification of women at risk for shorter
      breastfeeding duration may be useful in reversing this trend. OBJECTIVES: The
      aims of this study were to translate and psychometrically test the Swedish
      version of the Breastfeeding Self-Efficacy Scale-Short Form (BSES-SF), examine
      the relationship between breastfeeding self-efficacy and demographic variables,
      and evaluate associations with breastfeeding continuation plans in Swedish
      mothers. METHODS: The BSES-SF was translated into Swedish using forward and back
      translation. The sample consisted of 120 mothers who, during the first week
      postpartum, came for a routine follow-up visit at the postnatal unit in a
      university hospital. The mothers were compared based on demographic data and
      their future breastfeeding plans. RESULTS: The Cronbach's alpha coefficient for
      internal consistency for the BSES-SF was 0.91 and the majority of correlation
      coefficients exceeded 0.3. A 1-factor solution was found that explained 46% of
      the total variance. There was no difference in confidence in breastfeeding
      between mothers with early hospital discharge and mothers who received postnatal
      care at the hospital. Primiparas who stayed longer at the hospital were less
      confident in breastfeeding than primiparas who had a shorter hospital stay.
      Breastfeeding mothers who planned to partially breastfeed in the near future had
      lower BSES-SF scores, compared to those who planned to continue exclusive
      breastfeeding. CONCLUSION: The Swedish version of the BSES-SF has good
      reliability, validity, and agreement with mothers' plans regarding breastfeeding
      continuation and exclusivity.

PMID- 24574155
TI  - Nanosized heterostructures of Au@Prussian blue analogues: towards
      multifunctionality at the nanoscale.
AB  - Access to multifunctionality at the nanoscale requires the development of hybrid
      nanostructures that combine materials of different natures. In this line of
      thought, current research on coordination polymers is not only focusing on their
      synthesis at the nanoscale, but also on combining these polymers with other
      materials. According to a novel and rational approach, single-layer Au@Prussian
      blue analogue (PBA) and double-layer Au@PBA@PBA' core-shell nanoparticles (NPs)
      may be obtained through the growth of a cyano-bridged coordination network on the
      gold surface. The nanosized heterostructures combine the plasmonic optical
      properties of the gold core and the magnetic properties of the PBA shell. Whereas
      the single-layer nanoparticles are paramagnetic, the double-layer nanostructures
      display ferromagnetism; therefore, the overall structural motif may be considered
      as multifunctional. The developed synthetic concept also includes an easy access
      to hollow PBA NPs. 

PMID- 24574153
TI  - Respiratory muscle strength in healthy infants and those with surgically
      correctable anomalies.
AB  - Assessment of respiratory muscle strength provides important diagnostic and
      prognostic information. Normative data in healthy, term infants is, however,
      limited. Surgically correctable birth defects, congenital diaphragmatic hernia
      (CDH) and abdominal wall defects (AWD), commonly have impaired diaphragm
      function. The study aims were to obtain normative data for respiratory muscle
      strength in healthy, term born infants at birth and at 6 weeks postnatal age
      (PNA) and to investigate the influence of growth and maturation on inspiratory
      muscle strength in CDH/AWD infants. Maximal inspiratory (cPimax) and expiratory
      (cPemax) pressures during crying were measured at birth in 67 healthy, term born
      infants (mean (SD) gestational age (GA) 39.4 (1.7) weeks) and reassessed in 27 at
      6 weeks PNA. cPimax and functional residual capacity (FRC) (22.3 (4.2) ml/kg)
      were also measured in 23 infants with AWD/CDH (mean (SD) GA 36.9 (2.1) weeks) and
      reassessed in 16 at median (range) 6.5 (1.5-15) months PNA. In healthy infants,
      mean (SD) cPimax was 88.8 (19.33) cmH2 O and cPemax 61.8 (13.5) cmH2 O at birth,
      increasing significantly at followup to 100.9 (15.2) cmH2 O (P < 0.05) and 82.6
      (19.4) cmH2 O (P < 0.001) respectively. Mean (SD) cPimax was significantly lower
      (47.5 (22.4) cmH2 O, P < 0.0001) in AWD/CDH infants compared to healthy infants
      at birth but had increased significantly to 88.1 (27.6) cmH2 O (P < 0.0001) at
      followup which correlated significantly with increases in FRC (r(2)  = 0.33, P =
      0.0263). Infants with AWD and CDH have significantly reduced inspiratory muscle
      strength compared to healthy term born infants but strength increases markedly in
      early life.

PMID- 24574156
TI  - Development of a novel 96-well format for liquid-liquid microextraction and its
      application in the HPLC analysis of biological samples.
AB  - A novel 96-well liquid-liquid microextraction system combined with modern HPLC
      was developed and used for the simultaneous analysis of 96 biological samples.
      The system made use of hollow fibers, a 96-well plate, and a plastic base with a
      center hole and a side hole. One end of the hollow fiber was sealed, while the
      other end was attached to one of the holes positioned at the center for the
      plastic base. The needle was inserted into the liquid from inside or outside of
      the hollow fiber through the center or the side holes, respectively. The system
      was tested with plasma samples containing three compounds, acidic indomethacin,
      neutral dexamethasone, and basic propafenone. Some parameters, such as the kind
      and dimension of hollow fiber, pH and salt concentration of the donor phase, the
      selection of organic solvent for the acceptor phase, and the extraction time were
      investigated. Under the optimization conditions, the Log D and drug concentration
      of indomethacin, dexamethasone, and propafenone in plasma and urine samples were
      analyzed. Then, the methodology was validated. The results demonstrated that
      ng/mL levels could be exactly and rapidly analyzed by our system, which was
      equipped with an auto-injection sampler, making sample analysis more convenient. 

PMID- 24574157
TI  - Determination of levamisole, aminorex, and pemoline in plasma by means of liquid
      chromatography-mass spectrometry and application to a pharmacokinetic study of
      levamisole.
AB  - Levamisole is an anti-helminthic drug and gained forensic interest after it was
      found that it was used as a cocaine adulterant. A liquid chromatography-mass
      spectrometry (LC-MS) method for the determination of levamisole and its
      metabolite aminorex in human plasma is described. Selectivity is given;
      calibration curves were linear within a calibration range of 1 ng/mL-500 ng/mL.
      Limits of detection and quantification (LODs, LOQs) were 0.85 ng/mL for
      levamisole and 0.09 ng/mL, and 0.34 ng/mL for aminorex, respectively. Precision
      data was in accordance with the GTFCh guidelines. The validated method was
      successfully applied to study the pharmacokinetics of levamisole after
      administration of 100 mg of levamisole orally. Levamisole could be detected up to
      36 h after ingestion in serum, while aminorex never exceeded the LOQ. A one
      compartment model best described levamisole pharmacokinetics. The following
      parameters were calculated: ka = 1.2 [1/h], CL/F = 52 l/h, V/F = 347 l, f (renal)
      = 0.0005, t 1/2 = 2.0 h, AUC = 1923 ng/mL*h, cmax = 214 ng/mL, tmax = 1.98 h.
      Levamisole could be quantified in 42.5% of cocaine--positive plasma samples (2.2
      to 224 ng/mL). Aminorex was positive in only 11.3% of the cases; however, it was
      never found higher than the LOQ. Pemoline, another stimulant detected in horse
      urine samples after administration of levamisole, was not found either in serum
      or in urine of this pharmacokinetic study. In post-mortem cases, levamisole and
      aminorex could be detected in femoral blood and the urine of cocaine users.
      Pemoline was not detected.

PMID- 24574158
TI  - Fabrication of a heparin-PVA complex hydrogel for application as a vascular
      access.
AB  - A high hydrostatic pressure method, which can apply over 600 MPa pressure was
      employed for preparing a hydrogel of poly(vinyl alcohol) (PVA) loaded with
      heparin. The aim of this study was to fabricate a heparin-PVA hydrogel conduit
      and evaluate its potential for vascular access. Heparin-PVA complex hydrogel
      showed suppressed heparin release and prevented clot formation, depending on the
      molecular weight of the PVA. Strength of the hydrogel conduit was increased by
      embedding a Dacron mesh between two PVA layers. The tubular heparin-PVA complex
      hydrogel displayed a burst pressure of 750 mmHg. The tubular heparin-PVA complex
      hydrogel did not show any occlusion or burst for 2 weeks after implantation,
      implying that this heparin-PVA complex hydrogel shows high potential for use as a
      vascular access. This is the first report on the preparation of a multilayered
      PVA hydrogel with heparin embedded on one side only. The proposed approach could
      be expanded to the fabrication of various biomaterials for specific purposes.

PMID- 24574159
TI  - Genetic susceptibility to male infertility: news from genome-wide association
      studies.
AB  - A thorough understanding of the genetic basis of male infertility has eluded
      researchers in spite of significant efforts to identify novel genetic causes of
      the disease, particularly over the past decade. Approximately half of male factor
      infertility cases have no known cause; however, it is likely that the majority of
      idiopathic male factor infertility cases have some unidentified genetic basis.
      Well-established genetic causes of male infertility are limited to Y chromosome
      microdeletions and Klinefelter's syndrome, together accounting for 10-20% of
      cases of severe spermatogenic failure. In addition to these, several genetic
      polymorphisms have been demonstrated to be significantly associated with male
      infertility. The discovery of new genetic associations with male infertility has
      been hampered by two primary factors. First, most studies are underpowered
      because of insufficient sample size and ethnic and phenotypic heterogeneity.
      Second, most studies evaluate a single gene, an approach that is very inefficient
      in the context of male infertility, considering that many hundreds of genes are
      involved in the process of testicular development and spermatogenesis.
      Significant recent advances in microarray and next-generation sequencing
      technologies have enabled the application of whole-genome approaches to the study
      of male infertility. We recently performed a pilot genome-wide association study
      (GWAS) for severe spermatogenic failure, and several additional male infertility
      GWAS have since been published. More recently, genomic microarray tools have been
      applied to the association of copy number variants with male infertility. These
      studies are beginning to shed additional light on the genetic architecture of
      male infertility, and whole-genome studies have proven effective in identifying
      novel genetic causes of the disease. This review will discuss some of the recent
      findings of these whole-genome studies as well as future directions for this
      research that will likely be the most productive moving forward. 

PMID- 24574160
TI  - Successful treatment of pulmonary hemangioma with propranolol.
AB  - Pulmonary hemangioma is a rare benign tumor of the lungs. Airway hemangiomas in
      particular may lead to feeding difficulties, barking cough, stridor, respiratory
      distress, and even acute airway obstruction. Hence, such hemangiomas usually
      require early and aggressive treatment; however, the treatment modalities
      employed so far have been associated with their own co-morbidities and potential
      long-term adverse effects for the developing child. Here, we report a case of 9
      month-old girl who presented with dyspnea and diagnosed pulmonary hemangioma in
      the lower lobe of left lung. Propranolol is now used as a first line treatment
      for infantile hemangiomas by many practitioners so we experienced propranolol
      treatment. This case report argues the first case of pulmonary hemangioma treated
      with propranolol successfully.

PMID- 24574161
TI  - A continental risk assessment of West Nile virus under climate change.
AB  - Since first introduced to North America in 1999, West Nile virus (WNV) has spread
      rapidly across the continent, threatening wildlife populations and posing serious
      health risks to humans. While WNV incidence has been linked to environmental
      factors, particularly temperature and rainfall, little is known about how future
      climate change may affect the spread of the disease. Using available data on WNV
      infections in vectors and hosts collected from 2003-2011 and using a suite of 10
      species distribution models, weighted according to their predictive performance,
      we modeled the incidence of WNV under current climate conditions at a continental
      scale. Models were found to accurately predict spatial patterns of WNV that were
      then used to examine how future climate may affect the spread of the disease.
      Predictions were accurate for cases of human WNV infection in the following year
      (2012), with areas reporting infections having significantly higher probability
      of presence as predicted by our models. Projected geographic distributions of WNV
      in North America under future climate for 2050 and 2080 show an expansion of
      suitable climate for the disease, driven by warmer temperatures and lower annual
      precipitation that will result in the exposure of new and naive host populations
      to the virus with potentially serious consequences. Our risk assessment
      identifies current and future hotspots of West Nile virus where mitigation
      efforts should be focused and presents an important new approach for monitoring
      vector-borne disease under climate change. 

PMID- 24574162
TI  - Dismutational and global-minimum isomers of heavier 1,4
      dimetallatetrasilabenzenes of Group 14.
AB  - Aromatic species with heavier Group 14 elements show remarkable differences in
      terms of stability, structure, and reactivity. Herein we report our experimental
      and theoretical investigations regarding isomers of germanium- and tin-containing
      benzene analogues E2Si4R6 (E=Ge, Sn). The germanium-substituted dismutational
      isomer with a tricyclic six-membered scaffold is isolable, but unlike the
      homonuclear Si6 analogue slowly rearranges even at room temperature to give the
      propellane-type global minimum isomer. In case of E=Sn the dismutational isomer
      may be an intermediate on the pathway to the propellane-type species obtained,
      but cannot be detected even at low temperature. Unprecedentedly large chemical
      shift anisotropies in the (29)Si NMR spectra that increase from the Si6 species
      through Ge2Si4 to Sn2Si4 are rationalized by progressively larger paramagnetic
      term contributions to the chemical shift tensor as a result of diminishing HOMO
      LUMO gaps, which are also reflected in the absorption spectra, as well as by
      appearance and symmetry of these frontier orbitals.

PMID- 24574163
TI  - Fascin regulates chronic inflammation-related human colon carcinogenesis by
      inhibiting cell anoikis.
AB  - By a proteomics-based approach, we identified an overexpression of fascin in
      colon adenocarcinoma cells (FPCKpP-3) that developed from nontumorigenic human
      colonic adenoma cells (FPCK-1-1) and were converted to tumorigenic by foreign
      body-induced chronic inflammation in nude mice. Fascin overexpression was also
      observed in the tumors arising from rat intestinal epithelial cells (IEC 6)
      converted to tumorigenic in chronic inflammation which was induced in the same
      manner. Upregulation of fascin expression in FPCK-1-1 cells by transfection with
      sense fascin cDNA converted the cells tumorigenic, whereas antisense fascin-cDNA
      transfected FPCKpP-3 cells reduced fascin expression and lost their tumor-forming
      ability in vivo. The tumorigenic potential by fascin expression was consistent
      with their ability to survive and grow in the three-dimensional multicellular
      spheroids. We found that resistance to anoikis (apoptotic cell death as a
      consequence of insufficient cell-to-substrate interactions), which is represented
      by the three-dimensional growth of solid tumors in vivo, was regulated by fascin
      expression through caspase-dependent apoptotic signals. From these, we
      demonstrate that fascin is a potent suppressor to caspase-associated anoikis and
      accelerator of the conversion of colonic adenoma cells into adenocarcinoma cells
      by chronic inflammation. 

PMID- 24574165
TI  - Examining the Intersection Between Suicidal Behaviors and Intimate Partner
      Violence Among a Sample of Males Receiving Services From the Veterans Health
      Administration.
AB  - Veterans comprise 10% of the population, and suicide among Veterans has garnered
      national media and policy attention. Existing research suggests that intimate
      partner violence (IPV) is a risk factor for suicidal behaviors among some high
      risk populations. This report offers a new perspective: the intersection between
      Veterans' suicidal thoughts and IPV, both victimization and perpetration. The
      data were obtained from a northeast telephone survey of Veterans (n = 296) using
      Veterans Health Administration services and yielded a 27% participation rate.
      Findings suggest male Veterans who are IPV involved have increased odds of
      suicidal thoughts and behaviors. 

PMID- 24574164
TI  - mRNA and miRNA analyses in cytologically positive endobronchial ultrasound-guided
      transbronchial needle aspiration: implications for molecular staging in lung
      cancer patients.
AB  - BACKGROUND: Lung cancer is highly aggressive and tends to metastasize early.
      Therefore, accurate mediastinal staging is important for therapeutic decision
      making. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS
      TBNA) has emerged as a minimally invasive procedure for mediastinal lymph node
      sampling and cancer staging. Classical EBUS-TBNA cytology has been combined with
      molecular staging techniques to improve sensitivity and specificity. This study
      aimed to assess mRNA integrity in samples acquired by EBUS-TBNA in the clinics.
      As proof-of-principle experiments, we also investigated whether stable miRNA
      could be detected in these samples. METHODS: Integrity of mRNA isolated from
      tumor-positive EBUS-TBNA samples was assessed by calculating the RNA integrity
      number (RIN). In addition, 4 microRNAs were investigated (miRNA 21, miRNA 155,
      miRNA 200c, and miRNA 34a) because their relation to lung cancer has been
      documented recently. A group of patients with benign mediastinal lymphadenopathy
      served as a control. RESULTS: mRNA isolated from EBUS-TBNA samples was nearly
      completely degraded if handled under clinical conditions (RIN <5). Intact miRNA
      was detected in all samples, with no nonspecific amplification in negative
      control samples. miRNA 21 and miRNA 200c levels were significantly higher in
      tumor-positive than in control samples (miRNA 21: median, 325,678 [range, 34,822
      583,502] vs. 801,430 (range, 17,013-5,362,145]; P < .05; miRNA 200c: median,
      9,198 [range, 610-211,121] vs. 42,870 [range, 0-926,252]; P < .05). CONCLUSIONS:
      Under clinical conditions, mRNA detection is likely unsuitable for improving
      sensitivity of EBUS-TBNA-facilitated cancer staging. In contrast, detection of
      miRNA combined with EBUS-TBNA cytology may improve staging sensitivity.

PMID- 24574167
TI  - A high-throughput LC-MS/MS screen for GHRP in equine and human urine, featuring
      peptide derivatization for improved chromatography.
AB  - The growth hormone releasing peptides (GHRPs) hexarelin, ipamorelin,
      alexamorelin, GHRP-1, GHRP-2, GHRP-4, GHRP-5, and GHRP-6 are all synthetic met
      enkephalin analogues that include unnatural D-amino acids. They were designed
      specifically for their ability to stimulate growth hormone release and may serve
      as performance enhancing drugs. To regulate the use of these peptides within the
      horse racing industry and by human athletes, a method is presented for the
      extraction, derivatization, and detection of GHRPs from equine and human urine.
      This method takes advantage of a highly specific solid-phase extraction combined
      with a novel derivatization method to improve the chromatography of basic
      peptides. The method was validated with respect to linearity, repeatability,
      intermediate precision, specificity, limits of detection, limits of confirmation,
      ion suppression, and stability. As proof of principle, all eight GHRPs or their
      metabolites could be detected in urine collected from rats after intravenous
      administration.

PMID- 24574166
TI  - Validation of multiple-breath washout equipment for infants and young children.
AB  - INTRODUCTION: The new ATS/ERS consensus report recommends in vitro validation of
      multiple-breath inert gas washout (MBW) equipment based on a lung model with
      simulated physiologic conditions. We aimed to assess accuracy of two MBW setups
      for infants and young children using this model, and to compare functional
      residual capacity (FRC) from helium MBW (FRC(MBW)) with FRC from plethysmography
      (FRC(pleth)) in vivo. METHODS: The MBW setups were based on ultrasonic flow meter
      technology. Sulfur hexafluoride and helium were used as tracer gases. We measured
      FRC in vitro for specific model settings with and without carbon dioxide and
      calculated differences of measured to generated FRC. For in vivo evaluation,
      difference between FRC(MBW) and FRC(pleth) was calculated in 20 healthy children,
      median age 6.1 years. Coefficient of variation (CV) was calculated per FRC.
      RESULTS: In the infant model (51 runs, FRC 80-300 ml), mean (SD) relative
      difference between generated and measured FRCs was 0.7 (4.7) %, median CV was
      4.4% for measured FRCs. In the young child model, one setting (8 runs, FRC 400
      ml) showed a relative difference of up to 13%. For the remaining FRCs (42 runs,
      FRC 600-1,400 ml), mean (SD) relative difference was -2.0 (3.4) %; median CV was
      1.4% for measured FRCs. In vivo FRC(pleth) exceeded FRC(MBW) values by 37% on
      average. CONCLUSIONS: Both setups measure lung volumes in the intended age group
      reliably and reproducibly. Characteristics of different techniques should be
      considered when measuring lung volumes in vivo.

PMID- 24574168
TI  - Thermoplastic polyurethane/hydroxyapatite electrospun scaffolds for bone tissue
      engineering: effects of polymer properties and particle size.
AB  - Thermoplastic polyurethane (TPU)/hydroxyapatite (HA) scaffolds were fabricated
      via electrospinning. The effects of TPU properties and HA particle size on
      scaffold physical properties and osteoblast-like cell performance were
      investigated. It was found that the addition of micro-HA (mHA), which was inlayed
      in the fiber, decreased the electrospun fiber diameter. On the contrary, nano-HA
      (nHA), which was either embedded or existed inside of the fiber, increased the
      fiber diameter for both soft and hard TPUs. The soft TPU had a much lower Young's
      modulus and higher strain-at-break than the hard TPU. The addition of both mHA
      and nHA decreased the tensile properties; this decrease was more significant with
      mHA. The cells on the hard scaffolds actively proliferated and migrated compared
      to those on the soft scaffolds. On the other hand, cells on the soft scaffolds
      more effectively induced osteogenesis of human mesenchymal stem cells (hMSCs)
      than those on the hard scaffolds. In addition, our data suggest that the soft
      scaffolds with supplementation of nHA further enhanced osteogenesis of hMSCs
      compared to those without nHA. The soft TPU scaffolds containing nano-HA have the
      potential to be used in bone tissue engineering applications.

PMID- 24574169
TI  - Intratesticular testosterone is increased in men with Klinefelter syndrome and
      may not be released into the bloodstream owing to altered testicular
      vascularization- a preliminary report.
AB  - Klinefelter syndrome (KS, 47,XXY) is associated with low serum testosterone (T),
      long thought to arise from disturbed steroidogenesis in Leydig cells. However,
      intratesticular testosterone (ITT) concentrations were recently found to be
      normal in a KS mouse model(41,XXY*). So far, nothing was known about ITT
      concentrations in human patients with KS. Therefore, ITT, sex hormone-binding
      globulin (SHBG) and histological parameters were measured in human testicular
      biopsies of 11 KS patients, 30 azoospermic patients with Sertoli-cell-only
      syndrome and nine men with normal spermatogenesis as controls. ITT concentrations
      showed an overall pronounced excess over intratesticular SHBG in molar terms and
      were significantly increased in men with KS despite of reduced serum T levels.
      While the ratio of ITT/serum T was markedly increased in KS, the ITT/LH-ratio was
      comparable between all groups. After finding significantly increased ITT levels
      in men with KS, a finding even more striking than in the 41,XXY* KS mouse model,
      we set out to find a possible 'vascular' explanation for the lack of T release
      into the testicular blood stream. In testis biopsies from patients,reliable
      analysis of the vessels is, however, not possible because of the bias resulting
      from the dissection technique requiring avoidance of larger blood vessels to
      prevent bleeding. Consequently, the blood vessel constitution was evaluated in
      whole testis sections from adult male 41,XXY* and 40,XY*mice (n=5, each). Indeed,
      the blood vessel/testes surface ratio correcting for the smaller testes of
      XXY*mice was significantly lower in these mice compared with XY*controls. In
      conclusion, testicular T production does not seem to be impaired in men with KS.
      On the contrary, ITT concentrations are increased, but not because of increased
      SHBG activity. The data from the mouse model let us speculate that a reduced
      vascular bed might be involved in lower release of T into the blood stream.

PMID- 24574170
TI  - Crystal structures of the carborane dianions [1,4-(PhCB10H10C)2C6H4]2- and [1,4
      (PhCB10H10C)2C6F4]2- and the stabilizing role of the para-phenylene unit on 2n+3
      skeletal electron clusters.
AB  - While carboranes with 2 n+2 and 2 n+4 (n=number of skeletal atoms) skeletal
      electrons (SE) are widely known, little has been reported on carboranes with odd
      SE numbers. Electrochemical measurements on two-cage assemblies, where two C
      phenyl-ortho-carboranyl groups are linked by a para-phenylene or a para
      tetrafluorophenylene bridge, revealed two well separated and reversible two
      electron reduction waves indicating formation of stable dianions and tetraanions.
      The salts of the dianions were isolated by reduction with sodium metal and their
      unusual structures were determined by X-ray crystallography. The diamagnetic
      dianions contain two 2 n+3 SE clusters where each cluster has a notably long
      carborane C-carborane C distance of ca 2.4 A. The pi conjugation within the
      phenylene bridge plays an important role in the stabilization of these carboranes
      with odd SE counts. 

PMID- 24574171
TI  - Development and validation of two subject-specific finite element models of human
      head against three cadaveric experiments.
AB  - Head injury, being one of the main causes of death or permanent disability,
      continues to remain a major health problem with significant socioeconomic costs.
      Numerical simulations using the FEM offer a cost-effective method and alternative
      to experimental methods in the biomechanical studies of head injury. The present
      study aimed to develop two realistic subject-specific FEMs of the human head with
      detailed anatomical features from medical images (Model 1: without soft tissue
      and Model 2: with soft tissue and differentiation of white and gray matters) and
      to validate them against the intracranial pressure (ICP) and relative
      intracranial motion data of the three cadaver experimental tests. In general,
      both the simulated results were in reasonably good agreement with the
      experimental measured ICP and relative displacements, despite slight discrepancy
      in a few neutral density targets markers. Sensitivity analysis showed some
      variations in the brain's relative motion to the material properties or marker's
      location. The addition of soft tissue in Model 2 helped to damp out the
      oscillations of the model response. It was also found that, despite the
      fundamental anatomical differences between the two models, there existed little
      evident differences in the predicted ICP and relative displacements of the two
      models. This indicated that the advancements on the details of the extracranial
      features would not improve the model's predicting capabilities of brain injury.

PMID- 24574175
TI  - Label-free LC-MS/MS identification of phosphatidylglycerol-regulated proteins in
      Synechocystis sp. PCC6803.
AB  - We present a proteomics dataset combining SDS-PAGE prefractionation and data
      dependent LC-MS/MS that enables the identification of phosphatidylglycerol
      regulated proteins in the pgsA(-) mutant of Synechocystis sp. PCC6803, a
      cyanobacterium strain that grows with this indispensable phospholipid added
      exogenously. We searched the acquired raw data against a composite protein
      sequence database of Synechocystis using MASCOT, and employed Progenesis LC-MS
      software for label-free quantification based on extracted peptide intensities to
      detect changes in protein abundances upon phospholipid withdrawal. Protein
      identifications were validated using rigorous criteria, and our analysis of the
      dataset revealed 80 phosphatidylglycerol-regulated proteins involved in various
      cellular processes including photosynthesis, respiration, metabolism, transport,
      transcription, and translation. The data have been deposited to the
      ProteomeXchange with identifier PXD000363
      (http://proteomecentral.proteomexchange.org/dataset/PXD000363). 

PMID- 24574174
TI  - Supramolecular nanofibrils inhibit cancer progression in vitro and in vivo.
AB  - Self-assembly of small peptide derivatives affords supramolecular nanofibrils
      that possess characteristic features of amyloid oligomers. Acting as de novo
      amyloid oligomers, the nanofibrils effectively inhibit the tumor progression both
      in vitro and in vivo, which demonstrates a new type of anticancer approach and
      may provide new insights for inverse comorbidity between cancer and
      neurodegenerative diseases. 

PMID- 24574176
TI  - Cathepsin K overexpression modifies lung development in newborn mice.
AB  - Cathepsin K (CatK), contributes to the development of chronic lung disease in
      newborn infants, but the impact of CatK for the lungs may be multifaceted. We
      have previously demonstrated that low level of CatK is associated with newborn
      lung injury and CatK deficiency aggravates lung injury in hyperoxia-exposed
      newborn mice. Thus, we hypothesized that sustained/higher expression of CatK
      could ameliorate hyperoxia-induced injury and restrain the development of
      pulmonary fibrosis. We studied the lungs of newborn wild-type (WT) and CatK
      overexpressing transgenic mice (TG) that were exposed to hyperoxia or room air
      for 7 or 14 days after birth. Fourfold pulmonary overexpression of CatK did not
      affect the growth or lung weight in room-air bred TG mice. The distal airspaces
      in TG mice were, however, enlarged on postnatal days (PN) 7 and 14, the latter
      together with increased apoptosis, compared with WT controls. Survival rate was
      normal and no respiratory distress was observed in air-bred TG mice. Hyperoxia
      inhibited alveolarization and increased collagen accumulation in WT mice. In TG
      mice, hyperoxia for 1 week did not aggravate the lung injury, and the lung
      morphology and already enlarged alveoli remained unchanged in TG mice at PN7.
      Prolonged hyperoxic exposure caused significant lung injury and mortality
      similarly in both group of mice, and only few mice survived until PN14. In
      summary, CatK overexpression slightly enlarges distal airways in infant mice, but
      hyperoxic environment is initially better tolerated when compared to WT mice.
      These findings suggest multifaceted role for CatK in lung development and newborn
      lung injury.

PMID- 24574177
TI  - Space maintenance using crosslinked collagenated porcine bone grafted without a
      barrier membrane in one-wall intrabony defects.
AB  - The aim of this study was to determine the efficacy of crosslinked collagenated
      porcine bone (CPB) for the repair of surgically prepared one-wall intrabony
      defects in dogs. Buccolingually opened, one-wall, box-type periodontal defects (4
      * 5 mm) were prepared bilaterally at the mesial side of the mandibular fourth
      premolars in beagle dogs (N = 5). Block-type CPB (4 * 5 * 5 mm) was placed on
      either the left or right side for the CPB site; the opposite site served as a
      sham-surgery control. Micro-computed tomographic and histological analyses were
      performed on block specimens obtained from the dogs after a 3-month healing
      period. There was less mean bone regeneration and cementum regeneration at the
      experimental sites than at the sham-surgery control sites. Most of the porcine
      bone particles were located under the floor of the defect and were sequestered
      from pristine bone. These findings show that CPB can be localized within the
      defect during the wound-healing period by a process of crosslinking; however, the
      application of CPB alone without a barrier membrane may not be effective in
      promoting periodontal regeneration in noncontained-type defects.

PMID- 24574178
TI  - Modification of fluorescent photoinduced electron transfer (PET) sensors/switches
      to produce molecular photo-ionic triode action.
AB  - The fluorophore-spacer1-receptor1-spacer2-receptor2 system (where receptor2 alone
      is photoredox-inactive) shows ionically tunable proton-induced fluorescence off
      on switching, which is reminiscent of thermionic triode behavior. This also
      represents a new extension to modular switch systems based on photoinduced
      electron transfer (PET) towards the emulation of analogue electronic devices.

PMID- 24574179
TI  - Systematic review of restraint interventions for challenging behaviour among
      persons with intellectual disabilities: focus on effectiveness in single-case
      experiments.
AB  - BACKGROUND: This article is the first in a two-part series: we focus on the
      effectiveness of restraint interventions (RIs) for reducing challenging behaviour
      (CB) among persons with intellectual disabilities in this first article. In the
      second article, we focus on experiences with RIs for CB among people with
      intellectual disabilities. METHODS: A mixed-methods research synthesis involving
      statistical meta-analysis and qualitative meta-synthesis techniques was applied
      to synthesize 76 retrieved articles. This first article reports on the meta
      analysis of 59 single-case experiments (SCEs) on effectiveness of RIs for CB
      among people with intellectual disabilities. RESULTS AND CONCLUSIONS: The RIs
      reported on in the SCEs were on average highly effective in reducing CB for
      people with intellectual disabilities, and this reduction in CB was statistically
      significant. However, the effects vary significantly over the included
      participants, and the published data and reported outcomes are rather
      unrepresentative of the everyday use of RIs among persons with intellectual
      disabilities.

PMID- 24574183
TI  - The effect of an on-site vision examination on adherence to vision screening
      recommendations.
AB  - Vision screenings are intended to efficiently identify students with possible
      visual impairment and initiate a referral for diagnosis and treatment. In many
      cases, at-risk students do not access the recommended care or experience delays
      in receiving care. The purpose of this article is to report the effect on
      adherence to vision screening recommendations by providing the eye examination at
      the students' school and at no cost. Of the 1,306 students screened, 382 (29.2%)
      were identified with possible visual impairment. Parental consent for examination
      was obtained for 198 (51.8%) students. Our vision screening and examination
      program yielded similar adherence to follow-up as stand-alone vision screening
      programs. Future program considerations should address perceptual barriers that
      may be contributing to parental nonadherence to vision screening recommendations.

PMID- 24574184
TI  - Studying the influence of hydrogel injections into the infarcted left ventricle
      using the element-free Galerkin method.
AB  - Myocardial infarction is an increasing health problem worldwide. Because of an
      under-supply of blood, the cardiomyocytes in the affected region permanently lose
      their ability to contract. This in turn gradually weakens the overall heart
      function. A new therapeutic approach based on the injection of a gel into the
      infarcted area aims to support the healing and to inhibit adverse remodelling
      that can lead to heart failure. A computational model is the basis for obtaining
      a better understanding of the heart mechanics, in particular, how myocardial
      infarction and gel injections affect its pumping performance. A strain invariant
      based stored energy function is proposed to account for the passive mechanical
      behaviour of the model, which also makes provision for active contraction. To
      incorporate injections an additive homogenization approach is introduced. The
      numerical framework is developed using an in-house code based on the element-free
      Galerkin method. The main focus of this contribution is to investigate the
      influence of gel injections on the mechanics of the left ventricle during the
      diastolic filling and systolic isovolumetric (isochoric) contraction phases. It
      is found that gel injections are able to reduce the elevated fibre stresses
      caused by an infarct.

PMID- 24574180
TI  - Structural and biochemical modification of a collagen scaffold to selectively
      enhance MSC tenogenic, chondrogenic, and osteogenic differentiation.
AB  - Biomaterial approaches for engineering orthopedic interfaces such as the tendon
      bone junction (TBJ) are limited by a lack of understanding of how insoluble
      (microstructure, composition) and soluble regulators of stem cell fate work in
      concert to promote bioactivity and differentiation. One strategy for regenerating
      the interface is to design biomaterials containing spatially graded structural
      properties sufficient to induce divergent mesenchymal stem cell (MSC)
      differentiation into multiple interface-specific phenotypes. This work explores
      the hypothesis that selective structural modification to a 3D collagen
      glycosaminoglycan (CG) scaffold combined with biochemical supplementation can
      drive human bone-marrow-derived MSC differentiation down tenogenic, osteogenic,
      and chondrogenic lineages. Tenogenic differentiation is enhanced in geometrically
      anisotropic scaffolds versus a standard isotropic control. Notably, blebbistatin
      treatment abrogates this microstructurally driven effect. Further, enhanced
      osteogenic differentiation and new mineral synthesis are achieved by
      incorporation of a calcium phosphate mineral phase within the CG scaffold along
      with the use of osteogenic induction media. Finally, chondrogenic differentiation
      is optimally driven by combining chondrogenic induction media with a reduced
      density scaffold that promotes increased cellular condensation, significantly
      higher expression of chondrogenic genes, and increased GAG deposition. Together
      these data provide critical insight regarding design rules for elements of an
      integrated biomaterial platform for orthopedic interface regeneration. 

PMID- 24574185
TI  - Top-down mass spectrometry and hydrogen/deuterium exchange for comprehensive
      structural characterization of interferons: implications for biosimilars.
AB  - Rapid development in biopharmaceuticals has put high demands on analytical tools
      that can provide accurate and comprehensive characterization of protein drugs,
      including biosimilars. Although the enzyme digestion based "bottom-up" approach
      is usually the method of choice for this purpose, it only gives peptide-level
      information and sequence coverage is often incomplete. In this work, we used top
      down MS with electron capture dissociation (ECD) to characterize both the primary
      and higher order structures of a therapeutic protein interferon and its variants.
      Accurate mass measurement at the intact protein level combined with top-down ECD
      fragmentation enabled unambiguous protein sequence confirmation and
      identification of all PTMs. Combining hydrogen/deuterium exchange and rapid
      disulfide reduction with top-down ECD on the LC time scale, we have investigated
      the differences in higher order structure between the protein variants, as well
      as the impact of PTMs on protein conformation. 

PMID- 24574186
TI  - Chloral hydrate sedation for infant pulmonary function testing.

PMID- 24574188
TI  - Ruthenium-catalyzed trans-selective hydrostannation of alkynes.
AB  - In contrast to all other transition-metal-catalyzed hydrostannation reactions
      documented in the literature, the addition of Bu3SnH across various types of
      alkynes proceeds with excellent trans selectivity, provided the reaction is
      catalyzed by [Cp*Ru]-based complexes. This method is distinguished by a broad
      substrate scope and a remarkable compatibility with functional groups, including
      various substituents that would neither survive under the conditions of
      established Lewis acid mediated trans hydrostannations nor withstand free-radical
      reactions. In case of unsymmetrical alkynes, a cooperative effect between the
      proper catalyst and protic functionality in the substrate allows outstanding
      levels of regioselectivity to be secured as well.

PMID- 24574187
TI  - Osteogenic differentiation on DLC-PDMS-h surface.
AB  - The hypothesis was that anti-fouling diamond-like carbon polydimethylsiloxane
      hybrid (DLC-PDMS-h) surface impairs early and late cellular adhesion and matrix
      cell interactions. The effect of hybrid surface on cellular adhesion and
      cytoskeletal organization, important for osteogenesis of human mesenchymal
      stromal cells (hMSC), where therefore compared with plain DLC and titanium (Ti).
      hMSCs were induced to osteogenesis and followed over time using scanning electron
      microscopy (SEM), time-of-flight secondary ion mass spectrometry (ToF-SIMS),
      immunofluorescence staining, quantitative real-time polymerase chain reaction
      (qRT-PCR), and hydroxyapatite (HA) staining. SEM at 7.5 hours showed that initial
      adherence and spreading of hMSC was poor on DLC-PDMS-h. At 5 days some hMSC were
      undergoing condensation and apoptotic fragmentation, whereas cells on DLC and Ti
      grew well. DAPI-actin-vinculin triple staining disclosed dwarfed cells with
      poorly organized actin cytoskeleton-focal complex/adhesion-growth substrate
      attachments on hybrid coating, whereas spread cells, organized microfilament
      bundles, and focal adhesions were seen on DLC and in particular on Ti.
      Accordingly, at day one ToF-SIMS mass peaks showed poor protein adhesion to DLC
      PDMS-h compared with DLC and Ti. COL1A1, ALP, OP mRNA levels at days 0, 7, 14,
      21, and/or 28 and lack of HA deposition at day 28 demonstrated delayed or failed
      osteogenesis on DLC-PDMS-h. Anti-fouling DLC-PDMS-h is a poor cell adhesion
      substrate during the early protein adsorption-dependent phase and extracellular
      matrix-dependent late phase. Accordingly, some hMSCs underwent anoikis-type
      apoptosis and failed to complete osteogenesis, due to few focal adhesions and
      poor cell-to-ECM contacts. DLC-PDMS-h seems to be a suitable coating for non
      integrating implants/devices designed for temporary use.

PMID- 24574189
TI  - Peptide-directed spatial organization of biomolecules in dynamic gradient
      scaffolds.
AB  - Specific binding peptides are used to spatially organize biomolecule gradients
      within an electrospun fiber scaffold. Different biomolecule-binding peptide
      polymer conjugates are sequentially co-electrospun with a fiber-forming host
      polymer to generate opposing gradients of peptide functionalization. The binding
      peptides specifically and non-covalently guide the spatial arrangement of
      biomolecules into dynamic gradients within the scaffold, mimicking biological
      gradients found in native tissues. 

PMID- 24574190
TI  - Effect of the Mediterranean diet on heart failure biomarkers: a randomized sample
      from the PREDIMED trial.
AB  - AIMS: Scarce data are available on the effect of the traditional Mediterranean
      diet (TMD) on heart failure biomarkers. We assessed the effect of TMD on
      biomarkers related to heart failure in a high cardiovascular disease risk
      population. METHODS AND RESULTS: A total of 930 subjects at high cardiovascular
      risk (420 men and 510 women) were recruited in the framework of a multicentre,
      randomized, controlled, parallel-group clinical trial directed at testing the
      efficacy of the TMD on the primary prevention of cardiovascular disease (The
      PREDIMED Study). Participants were assigned to a low-fat diet (control, n = 310)
      or one of two TMDs [TMD + virgin olive oil (VOO) or TMD + nuts]. Depending on
      group assignment, participants received free provision of extra-virgin olive oil,
      mixed nuts, or small non-food gifts. After 1 year of intervention, both TMDs
      decreased plasma N-terminal pro-brain natriuretic peptide, with changes reaching
      significance vs. control group (P < 0.05). Oxidized low-density lipoprotein
      decreased in both TMD groups (P < 0.05), the decrease in TMD + VOO group reaching
      significance vs. changes in control group (P = 0.003). Changes in lipoprotein(a)
      after TMD + VOO were less than those in the control group (P = 0.046) in which an
      increase (P = 0.035) was observed. No changes were observed in urinary albumin or
      albumin/creatinine ratio. CONCLUSIONS: Individuals at high risk of cardiovascular
      disease (CVD) who improved their diet toward a TMD pattern reduced their N
      terminal pro-brain natriuretic peptide compared with those assigned to a low-fat
      diet. The same was found for in vivo oxidized low-density lipoprotein and
      lipoprotein(a) plasma concentrations after the TMD + VOO diet. From our results
      TMD could be a useful tool to mitigate against risk factors for heart failure.
      From our results TMD could modify markers of heart failure towards a more
      protective mode.

PMID- 24574191
TI  - A fast alternating direction implicit algorithm for geometric flow equations in
      biomolecular surface generation.
AB  - In this paper, a new alternating direction implicit (ADI) method is introduced to
      solve potential driven geometric flow PDEs for biomolecular surface generation.
      For such PDEs, an extra factor is usually added to stabilize the explicit time
      integration. However, two existing implicit ADI schemes are also based on the
      scaled form, which involves nonlinear cross derivative terms that have to be
      evaluated explicitly. This affects the stability and accuracy of these ADI
      schemes. To overcome these difficulties, we propose a new ADI algorithm based on
      the unscaled form so that cross derivatives are not involved. Central finite
      differences are employed to discretize the nonhomogenous diffusion process of the
      geometric flow. The proposed ADI algorithm is validated through benchmark
      examples with analytical solutions, reference solutions, or literature results.
      Moreover, quantitative indicators of a biomolecular surface, including surface
      area, surface-enclosed volume, and solvation free energy, are analyzed for
      various proteins. The proposed ADI method is found to be unconditionally stable
      and more accurate than the existing ADI schemes in all tests. This enables the
      use of a large time increment in the steady state simulation so that the proposed
      ADI algorithm is very efficient for biomolecular surface generation.

PMID- 24574192
TI  - Combined visual and motor evoked potentials predict multiple sclerosis disability
      after 20 years.
AB  - BACKGROUND: The development of predictors of multiple sclerosis (MS) disability
      is difficult due to the complex interplay of pathophysiological and adaptive
      processes. OBJECTIVE: The purpose of this study was to investigate whether
      combined evoked potential (EP)-measures allow prediction of MS disability after
      20 years. METHODS: We examined 28 patients with clinically definite MS according
      to Poser's criteria with Expanded Disability Status Scale (EDSS) scores, combined
      visual and motor EPs at entry (T0), 6 (T1), 12 (T2) and 24 (T3) months, and a
      cranial magnetic resonance imaging (MRI) scan at T0 and T2. EDSS testing was
      repeated at year 14 (T4) and year 20 (T5). Spearman rank correlation was used. We
      performed a multivariable regression analysis to examine predictive relationships
      of the sum of z-transformed EP latencies (s-EPT0) and other baseline variables
      with EDSST5. RESULTS: We found that s-EPT0 correlated with EDSST5 (rho=0.72,
      p<0.0001) and DeltaEDSST5-T0 (rho=0.50, p=0.006). Backward selection resulted in
      the prediction model: E (EDSST5)=3.91-2.22*therapy+0.079*age+0.057*s-EPT0 (Model
      1, R (2)=0.58) with therapy as binary variable (1=any disease-modifying therapy
      between T3 and T5, 0=no therapy). Neither EDSST0 nor T2-lesion or gadolinium (Gd)
      enhancing lesion quantities at T0 improved prediction of EDSST5. The area under
      the receiver operating characteristic (ROC) curve was 0.89 for model 1.
      CONCLUSIONS: These results further support a role for combined EP-measures as
      predictors of long-term disability in MS.

PMID- 24574193
TI  - Impact of a short early therapeutic education program on the quality of life of
      asthmatic children and their families.
AB  - OBJECTIVES: Few studies have been made on the impact of therapeutic education
      (TE) on the quality of life (QOL) of asthmatic primary-school aged children. We
      attempted to assess the beneficial effects on the QOL of children and their
      parents of a short TE program initiated immediately after the first consultation
      with a pediatric pulmonologist. METHODS: The QOL of 31 families of asthmatic
      children (aged 5-11) was measured before and 3 months after a short and early
      programme of TE by the French version of the Pictured Child's Quality of Life
      Self Questionnaire (AUQUEI, AUtoquestionnaire QUalite de vie Enfant Image) for
      the children, and by the Paediatric Asthma Caregiver's Quality of Life
      Questionnaire (PACQLQ) for the parents. The other criteria studied were asthma
      management, school and workplace absenteeism and functional respiratory
      parameters. RESULTS: TE did not significantly alter the AUQUEI score (P = 0.67).
      No change was observed in the different areas studied: autonomy (P = 0.97),
      leisure activities (P = 0.64), functions (P = 0.88), and social relations (P =
      0.51). In contrast, the PACQLQ score considerably improved after TE (P < 0.001),
      as evidenced by reduced activity limitations (P < 0.001) and improved emotional
      functioning of parents (P < 0.001). These results were accompanied by a
      significant improvement in asthma management, with, in particular, a major
      decrease in the use of medication (P < 0.001) and the number of unscheduled
      medical consultations (P < 0.001) and visits to the emergency department (P =
      0.02); a decrease in school absenteeism (P = 0.009); and an improvement in forced
      expiratory volume in 1 sec (FEV1 ) (P = 0.05). CONCLUSIONS: Our TE program had
      rapid and beneficial effects on numerous objective and subjective parameters,
      thereby contributing to the well-being of the families and probably to a
      subsequent decrease in the overall cost of asthma management. Pediatr Pulmonol.
      2015; 50:213-221. (c) 2014 Wiley Periodicals, Inc.

PMID- 24574194
TI  - Thermally-active screw dislocations in Si nanowires and nanotubes.

PMID- 24574195
TI  - Imaging: high relaxivities and strong vascular signal enhancement for NaGdF4
      nanoparticles designed for dual MR/optical imaging (Adv. Healthcare Mater.
      11/2013).
AB  - Tripositive gadolinium-ion doped NIR-to-NIR upconverting paramagnetic
      nanoparticles are efficiently detected are NIR imaging techniques but can also
      provide efficient "positive" contrast in MRI. On page 1478 John A. Capobianco,
      Marc-Andre Fortin, and co-workers show that citrate-coated nanoparticles present
      the lowest relaxometric ratios reported for NaGdF4 nanoparticle suspensions. IV
      injected nanoparticles evidence long blood retention times in mice while
      biodistribution studies show elimination through the reticuloendothelial and
      urinary systems. 

PMID- 24574196
TI  - Enhanced intracellular siRNA delivery using bioreducible lipid-like
      nanoparticles.
AB  - A new library of lipid-like nanoparticles (lipidoids) comprising disulfide bond
      is developed for siRNA delivery. Bioreducible lipidoids deliver siRNA with
      greater efficiency than nonbioreducible lipidoids with similar chemical
      structures. A siRNA release investigation, as well as an intracellular siRNA
      trafficking study, reveals that the degradation of bioreducible lipidoid in a
      strongly reductive intracellular environment boosts siRNA release and enhances
      siRNA gene knockdown efficiency. 

PMID- 24574197
TI  - Gas-phase peptide structures unraveled by far-IR spectroscopy: combining IR-UV
      ion-dip experiments with Born-Oppenheimer molecular dynamics simulations.
AB  - Vibrational spectroscopy provides an important probe of the three-dimensional
      structures of peptides. With increasing size, these IR spectra become very
      complex and to extract structural information, comparison with theoretical
      spectra is essential. Harmonic DFT calculations have become a common workhorse
      for predicting vibrational frequencies of small neutral and ionized gaseous
      peptides. Although the far-IR region (<500 cm(-1)) may contain a wealth of
      structural information, as recognized in condensed phase studies, DFT often
      performs poorly in predicting the far-IR spectra of peptides. Here, Born
      Oppenheimer molecular dynamics (BOMD) is applied to predict the far-IR signatures
      of two gamma-turn peptides. Combining experiments and simulations, far-IR spectra
      can provide structural information on gas-phase peptides superior to that
      extracted from mid-IR and amide A features.

PMID- 24574198
TI  - A perspective on re-evaluating digoxin's role in the current management of
      patients with chronic systolic heart failure: targeting serum concentration to
      reduce hospitalization and improve safety profile.
AB  - Digoxin improves exercise tolerance and reduces hospitalizations in patients with
      systolic heart failure, but its use has declined progressively for the past two
      decades. The Digitalis Investigation Group trial showed that digoxin reduced
      hospitalizations but had a neutral effect on total mortality. There was evidence
      that mortality caused by worsening heart failure was less, but there was also a
      signal suggesting an increase in other cardiac (presumed arrhythmic) death. Use
      of digoxin has declined substantially and recent guideline recommendations have
      significantly de-emphasized the importance of this drug in the management of
      heart failure. Two developments suggest that re-evaluation of the contemporary
      role of digoxin in the management of heart failure with reduced ejection fraction
      is warranted. First, heart failure remains progressive, characterized by chronic
      debility, exercise intolerance, and frequent and costly hospitalizations, despite
      evidence-based drug and device therapies that prolong survival. Health economics
      have made reducing hospitalizations in patients with heart failure a major
      priority. Second, a strong association has emerged between serum concentration
      and the safety and efficacy of digoxin, which indicates a change in our approach
      to dosing this agent is needed. Experimental and clinical results suggest that
      optimizing therapeutic benefit and avoiding harm means dosing to achieve low
      serum digoxin concentrations (0.5-0.9 ng/mL). Digoxin is an inexpensive agent and
      the totality of evidence indicates that it reduces hospitalizations and improves
      symptoms safely when dosed to achieve low serum concentrations. These findings
      suggest digoxin should have a more prominent therapeutic role in patients with
      heart failure and reduced ejection fraction. 

PMID- 24574199
TI  - Compound eyes of insects and crustaceans: Some examples that show there is still
      a lot of work left to be done.
AB  - Similarities and differences between the 2 main kinds of compound eye (apposition
      and superposition) are briefly explained before several promising topics for
      research on compound eyes are being introduced. Research on the embryology and
      molecular control of the development of the insect clear-zone eye with
      superposition optics is one of the suggestions, because almost all of the
      developmental work on insect eyes in the past has focused on eyes with apposition
      optics. Age- and habitat-related ultrastructural studies of the retinal
      organization are another suggestion and the deer cad Lipoptena cervi, which has
      an aerial phase during which it is winged followed by a several months long
      parasitic phase during which it is wingless, is mentioned as a candidate species.
      Sexual dimorphism expressing itself in many species as a difference in eye
      structure and function provides another promising field for compound eye
      researchers and so is a focus on compound eye miniaturization in very small
      insects, especially those that are aquatic and belong to species, in which clear
      zone eyes are diagnostic or are tiny insects that are not aquatic, but belong to
      taxa like the Diptera for instance, in which open rather than closed rhabdoms are
      the rule. Structures like interommatidial hairs and glands as well as corneal
      microridges are yet another field that could yield interesting results and in the
      past has received insufficient consideration. Finally, the dearth of information
      on distance vision and depth perception is mentioned and a plea is made to
      examine the photic environment inside the foam shelters of spittle bugs,
      chrysales of pupae and other structures shielding insects and crustaceans. 

PMID- 24574200
TI  - Age-related changes in conjunctive visual search in children with and without
      ASD.
AB  - Visual-spatial strengths observed among people with autism spectrum disorder
      (ASD) may be associated with increased efficiency of selective attention
      mechanisms such as visual search. In a series of studies, researchers examined
      the visual search of targets that share features with distractors in a visual
      array and concluded that people with ASD showed enhanced performance on visual
      search tasks. However, methodological limitations, the small sample sizes, and
      the lack of developmental analysis have tempered the interpretations of these
      results. In this study, we specifically addressed age-related changes in visual
      search. We examined conjunctive visual search in groups of children with (n = 34)
      and without ASD (n = 35) at 7-9 years of age when visual search performance is
      beginning to improve, and later, at 10-12 years, when performance has improved.
      The results were consistent with previous developmental findings; 10- to 12-year
      old children were significantly faster visual searchers than their 7- to 9-year
      old counterparts. However, we found no evidence of enhanced search performance
      among the children with ASD at either the younger or older ages. More research is
      needed to understand the development of visual search in both children with and
      without ASD.

PMID- 24574201
TI  - Effects of the ambient temperature on the airflow across a Caucasian nasal
      cavity.
AB  - We analyse the effects of the air ambient temperature on the airflow across a
      Caucasian nasal cavity under different ambient temperatures using CFD
      simulations. A three-dimensional nasal model was constructed from high-resolution
      computed tomography images for a nasal cavity from a Caucasian male adult. An
      exhaustive parametric study was performed to analyse the laminar-compressible
      flow driven by two different pressure drops between the nostrils and the
      nasopharynx, which induced calm breathing flow rates ? 5.7 L/min and ? 11.3
      L/min. The inlet air temperature covered the range - 10(o) C ? To ?50(o) C. We
      observed that, keeping constant the wall temperature of the nasal cavity at 37(o)
      C, the ambient temperature affects mainly the airflow velocity into the valve
      region. Surprisingly, we found an excellent linear relationship between the
      ambient temperature and the air average temperature reached at different cross
      sections, independently of the pressure drop applied. Finally, we have also
      observed that the spatial evolution of the mean temperature data along the nasal
      cavity can be collapsed for all ambient temperatures analysed with the
      introduction of suitable dimensionless variables, and this evolution can be
      modelled with the help of hyperbolic functions, which are based on the heat
      exchanger theory.

PMID- 24574202
TI  - CMOS-compatible silicon nanowire field-effect transistors for ultrasensitive and
      label-free microRNAs sensing.
AB  - MicroRNAs (miRNAs) have been regarded as promising biomarkers for the diagnosis
      and prognosis of early-stage cancer as their expression levels are associated
      with different types of human cancers. However, it is a challenge to produce low
      cost miRNA sensors, as well as retain a high sensitivity, both of which are
      essential factors that must be considered in fabricating nanoscale biosensors and
      in future biomedical applications. To address such challenges, we develop a
      complementary metal oxide semiconductor (CMOS)-compatible SiNW-FET biosensor
      fabricated by an anisotropic wet etching technology with self-limitation which
      provides a much lower manufacturing cost and an ultrahigh sensitivity. This
      nanosensor shows a rapid (< 1 minute) detection of miR-21 and miR-205, with a low
      limit of detection (LOD) of 1 zeptomole (ca. 600 copies), as well as an excellent
      discrimination for single-nucleotide mismatched sequences of tumor-associated
      miRNAs. To investigate its applicability in real settings, we have detected
      miRNAs in total RNA extracted from lung cancer cells as well as human serum
      samples using the nanosensors, which demonstrates their potential use in
      identifying clinical samples for early diagnosis of cancer. 

PMID- 24574203
TI  - Community treatment orders: implications of the drafting of the Mental Health Act
      2007 for emergency detention of community patients.
AB  - Since the introduction of Community Treatment Orders by the Mental Health Act
      2007, their use has increased year on year. Clinical experience has, however,
      demonstrated a weakness in the drafting of the Act, particularly in respect of
      patients who may be admitted informally for treatment of their mental health
      while also on a Community Treatment Order and then require detention under the
      terms of the Mental Health Act 2007. This paper describes these potential
      problems, particularly with regard to the inability to detain a Community Patient
      using sections 4 or 5 of the MHA 2007. The authors explore the difficulties that
      may arise from this, including the need to balance the principle of using the
      least restrictive option, and the rights of the patient against the potential
      risks to both the patient and the public. The authors propose possible
      considerations and options in these circumstances. 

PMID- 24574204
TI  - Proteomic biomarkers of recovered heart function.
AB  - AIMS: Chronic heart failure is a costly epidemic that affects up to 2% of people
      in developed countries. The purpose of this study was to discover novel blood
      proteomic biomarker signatures of recovered heart function that could lead to
      more effective heart failure patient management by both primary care and
      specialty physicians. METHODS AND RESULTS: The discovery cohort included 41 heart
      transplant patients and 20 healthy individuals. Plasma levels of 138 proteins
      were detected in at least 75% of these subjects by iTRAQ mass spectrometry.
      Eighteen proteins were identified that had (i) differential levels between pre
      transplant patients with end-stage heart failure and healthy individuals; and
      (ii) levels that returned to normal by 1 month post-transplant in patients with
      stable heart function after transplantation. Seventeen of the 18 markers were
      validated by multiple reaction monitoring mass spectrometry in a cohort of 39
      heart failure patients treated with drug therapy, of which 30 had recovered heart
      function and 9 had not. This 17-protein biomarker panel had 93% sensitivity and
      89% specificity, while the RAMP(r) NT-proBNP assay had the same specificity but
      80% sensitivity. Performance further improved when the panel was combined with NT
      proBNP, yielding a net reclassification index relative to NT-proBNP of 0.28.
      CONCLUSIONS: We have identified potential blood biomarkers of recovered heart
      function by harnessing data from transplant patients. These biomarkers can lead
      to the development of an inexpensive protein-based blood test that could be used
      by physicians to monitor response to therapy in heart failure, resulting in more
      personalized, front-line heart failure patient management.

PMID- 24574205
TI  - Editorial: toll-like receptor 7: more than skin deep?

PMID- 24574206
TI  - Editorial: molecular insights into systemic sclerosis-associated interstitial
      lung disease.

PMID- 24574207
TI  - Increased surgeon experience with rheumatoid arthritis reduces the risk of
      complications following total joint arthroplasty.
AB  - OBJECTIVE: To determine the relationship between surgeon experience with, and
      complications following, total joint arthroplasty (TJA) in patients with
      rheumatoid arthritis (RA). METHODS: Using administrative data, we assembled a
      cohort of patients with RA who had undergone at least 1 elective primary hip or
      knee replacement procedure between 2002 and 2009. Cox proportional hazards,
      censored on death and accounting for clustering of patients within surgeons, were
      used to determine the relationship between overall and "RA-specific" surgeon TJA
      volume and the occurrence of a composite "complication" outcome (revision,
      infection, dislocation, or periprosthetic fracture within 2 years of the initial
      TJA), controlling for potential confounders (patient age, sex, comorbidity, and
      disease severity). RESULTS: We identified 4,762 patients with RA who were
      eligible for TJAs (1,515 total hip arthroplasties and 3,247 total knee
      arthroplasties). Among these patients, 152 (3.2%) experienced a surgical
      complication within 2 years of the procedure. After controlling for patient and
      hospital factors, greater surgeon TJA volume in patients with RA (RA TJA), but
      not overall TJA volume (all TJA), was associated with a reduced risk of
      complications (for surgeon RA TJA volume per 10 cases, adjusted hazard ratio [HR]
      0.81, 95% confidence interval [95% CI] 0.71-0.93, P = 0.002; for surgeon all TJA
      volume, adjusted HR 0.98, 95% CI 0.97-1.00, P = 0.09). CONCLUSION: In a cohort of
      patients with RA who underwent hip or knee TJA, increased surgeon experience
      performing TJA in patients with RA, irrespective of their overall TJA experience
      and hospital factors, was associated with a decreased risk of surgical
      complications. These findings have potential implications for surgeon training
      and the referral practices of rheumatologists.

PMID- 24574208
TI  - Determinants of mortality among postmenopausal women in the women's health
      initiative who report rheumatoid arthritis.
AB  - OBJECTIVE: Rheumatoid arthritis (RA) patients have an increased risk of
      cardiovascular disease (CVD) and mortality. We measured anti-cyclic citrullinated
      peptide (anti-CCP) antibody levels and determined use of disease-modifying
      antirheumatic drugs (DMARDs) among women in the Women's Health Initiative (WHI).
      Using these data, we undertook this study to assess total mortality over 10 years
      of followup among white, black, or Hispanic women with self-reported RA in the
      WHI. METHODS: Using stored baseline serum, we measured anti-CCP, rheumatoid
      factor (RF), and antinuclear antibodies (ANAs) in 9,988 women who reported having
      RA. Based on a previous chart review study, probable RA was defined as either
      self-reported RA and anti-CCP positivity, or anti-CCP negativity and DMARD use.
      Cox proportional hazards regression was used to model the relationship of self
      reported RA, DMARD exposure, and anti-CCP positivity to total mortality, using
      followup data through April 2009. RESULTS: At baseline, the mean age was 62.8
      years; 24.5% of subjects were black and 10% were Hispanic. Prevalence of anti-CCP
      positivity was 8.1% (n = 812), and 217 women were anti-CCP negative but had
      reported use of DMARDs; therefore, 1,029 women (of 9,988) were classified as
      having probable RA, and 8,958 were classified as unlikely to have RA (with data
      on DMARD use missing for 1 subject). Age-adjusted mortality rates were ~2-fold
      higher for anti-CCP-positive women, with 20.2 deaths per 1,000 person-years, as
      compared to 11.4 deaths per 1,000 person-years among anti-CCP-negative women with
      self-reported RA who never used DMARDs. Among women who did not report any
      arthritis at baseline, we found 8.3 deaths per 1,000 person-years. The increased
      risk among anti-CCP-positive women with RA was not explained by age, RF
      positivity, ANA positivity, or DMARD use. CONCLUSION: Anti-CCP-positive RA was
      associated with substantial excess mortality among postmenopausal women in the
      WHI. This result was not explained by the risk factors we measured.

PMID- 24574209
TI  - Adverse pregnancy outcomes and risk of subsequent rheumatoid arthritis.
AB  - OBJECTIVE: Pregnancy and reproductive outcomes have been associated with altered
      risk of some autoimmune diseases, including rheumatoid arthritis (RA). We sought
      to determine whether prior pregnancy resulting in a low birth weight (LBW) infant
      or preterm birth is associated with a risk of subsequent RA in the mother.
      METHODS: We conducted an analysis of RA risk in parous women from a population
      based prospective study of newly diagnosed cases of RA and age-matched healthy
      controls. The primary outcome measure was disease status (RA versus control),
      with exposures of prior preterm birth and prior delivery of an infant with LBW
      (<=2,500 gm), very low birth weight (VLBW; <=1,500 gm), or extremely low birth
      weight (ELBW; <=1,000 gm). A preplanned analysis including only rheumatoid factor
      (RF)-positive RA cases was also conducted. RESULTS: A total of 202 RA cases and
      1,102 controls were analyzed. Prior delivery of an infant with ELBW was
      associated with RA in the mother (relative risk [RR] 3.7 [95% confidence interval
      (95% CI) 1.0-13.2]). Prior VLBW (RR 4.0 [95% CI 1.3-11.4]) and ELBW (RR 5.5 [95%
      CI 1.4-22.5]) infants were associated with RF-positive RA. Prior LBW deliveries
      and preterm births were more common among RA cases than controls, but the
      differences were not statistically significant. CONCLUSION: Compared to those
      with uncomplicated pregnancies, women with a prior VLBW or ELBW delivery had a
      higher risk of RA, particularly RF-positive RA. This association may reflect
      common risk factors for pregnancy complications and RA. Alternatively,
      complicated pregnancy itself may confer risk of subsequent RA.

PMID- 24574211
TI  - Ultrasound assessment of synovial pathologic features in rheumatoid arthritis
      using comprehensive multiplane images of the second metacarpophalangeal joint:
      identification of the components that are reliable and influential on the global
      assessment of the whole joint.
AB  - OBJECTIVE: The aim of this pilot study was to provide groundwork that could be
      utilized to optimize the global ultrasound (US) assessment of the whole joint for
      synovial pathologic features in patients with rheumatoid arthritis (RA). METHODS:
      US images of the second metacarpophalangeal joint in 8 predefined imaging planes,
      comprising regions that comprehensively capture the synovial pathologic features
      of the whole joint, were obtained from 30 patients with RA. Twelve experienced
      sonographers evaluated these images at the level of both the individual image and
      the whole joint, using a visual analog scale (VAS) to assess pathologic severity.
      Interrater reproducibility of the VAS scores was evaluated with intraclass
      correlation coefficients (ICCs), and factors that independently influenced the
      global assessment of the whole joint were identified using multiple linear
      regression analysis. RESULTS: A total of 14,276 VAS scores were analyzed.
      Interrater reproducibility of any eligible VAS assessment of synovial pathologic
      features was good (ICC 0.65). US assessment of synovial pathologic features in
      joints with mild inflammation was less reproducible than that in joints with
      severe inflammation. Although the most severely affected region in a joint did
      not always represent the average pathologic severity among the 8 regions, global
      assessment of the whole joint strongly correlated with assessment of the most
      severely affected region (P < 0.001). Importantly, the standard, midline imaging
      plane was not the most influential plane on the global assessment of the whole
      joint. Assessment of synovial fluid accumulation was not reproducible (ICCs 0.20
      0.42) and did not substantially influence the global assessment of synovial
      inflammation (beta = 0.06). CONCLUSION: The results of this study provide a
      unique data set that could be utilized to optimize the global US assessment of
      synovial pathologic features of the whole joint in patients with RA.

PMID- 24574210
TI  - Features of the synovium of individuals at risk of developing rheumatoid
      arthritis: implications for understanding preclinical rheumatoid arthritis.
AB  - OBJECTIVE: Findings from previous studies have suggested that subclinical
      inflammation of the synovium does not coincide with the appearance of rheumatoid
      arthritis (RA)-specific autoantibodies. This study was undertaken to examine the
      relationship between the presence of autoantibodies, changes in the synovium, and
      development of arthritis over time in a markedly larger, prospective study.
      METHODS: Fifty-five individuals who were IgM rheumatoid factor positive and/or
      anti-citrullinated protein antibody (ACPA) positive (detected by the anti-cyclic
      citrullinated peptide antibody test) and who were without any evidence of
      arthritis upon physical examination were included in the study. ACPAs were
      subsequently also detected using a multiplex chip-based assay. All individuals
      underwent magnetic resonance imaging and mini-arthroscopic synovial biopsy
      sampling of a knee joint at inclusion and were prospectively followed up.
      Proportional hazards regression analysis was performed to investigate whether
      changes in the synovium were associated with the onset of arthritis. RESULTS:
      Fifteen individuals (27%) developed arthritis after a median followup time of 13
      months (interquartile range 6-27 months; range 1-47 months). No overt synovial
      inflammation was observed, but CD3+ T cell numbers in the biopsy tissue showed a
      borderline association with subsequent development of clinically manifest
      arthritis (hazard ratio 2.8, 95% confidence interval [95% CI] 0.9-9.1; P =
      0.088). In addition, the presence of CD8+ T cells was associated with ACPA
      positivity (odds ratio [OR] 16.0, 95% CI 1.7-151.1) and with the total number of
      ACPAs present (OR 1.4, 95% CI 1.0-1.8). CONCLUSION: These findings confirm and
      extend previous results showing the absence of clearcut synovial inflammation in
      individuals having systemic autoimmunity associated with RA. However, subtle
      infiltration by synovial T cells may precede the signs and symptoms of arthritis
      in preclinical RA.

PMID- 24574212
TI  - Brief report: does medication use or disease activity during pregnancy in
      patients with rheumatoid arthritis affect bone density in their prepubertal
      offspring?
AB  - OBJECTIVE: Prednisone use and active disease are associated with reduced bone
      mineral density (BMD) in patients with rheumatoid arthritis (RA). Either or both
      of these factors may be inevitable during pregnancy in women with RA, but it is
      unknown whether they variables influence the BMD of the offspring. This study was
      undertaken to investigate whether medication use or disease activity during
      pregnancy in RA patients influences the BMD of their prepubertal offspring.
      METHODS: Mothers (n = 255) participated in a prospective cohort study of RA and
      pregnancy, and 108 children of these mothers (ages 5-10 years) were included in
      this followup study. Information on features known to influence BMD in children,
      i.e., calcium intake, physical activity, serum 25-hydroxyvitamin D level, sex,
      height, and weight, was collected. In addition, pre- and postnatal variables
      known to influence BMD, i.e., gestational age, maternal smoking, birth weight,
      postnatal rate of growth, and type of feeding, were recorded. Independent
      variables were prednisone use, sulfasalazine use, and RA disease activity during
      pregnancy. RESULTS: We found no association of BMD in the children with either
      prednisone use or RA disease activity during pregnancy, even after correcting for
      all known associated variables. Sulfasalazine use during pregnancy had a positive
      effect on the total-body BMD of the offspring (difference in standard deviation
      score 0.53, P = 0.005). CONCLUSION: Our findings indicate that neither medication
      use nor high RA disease activity during pregnancy is associated with decreased
      BMD in offspring at age ~7 years. The maternal benefit of medication use for RA
      during pregnancy outweighs the effect on BMD in the offspring.

PMID- 24574213
TI  - Reciprocal activation of CD4+ T cells and synovial fibroblasts by stromal cell
      derived factor 1 promotes RANKL expression and osteoclastogenesis in rheumatoid
      arthritis.
AB  - OBJECTIVE: Stromal cell-derived factor 1 (SDF-1) is a chemokine that is involved
      in the bone-destructive process in rheumatoid arthritis (RA) and bony metastasis
      in malignancy. This study was undertaken to determine the role and mechanism of
      SDF-1 in RA-associated osteoclastogenesis. METHODS: The expression of SDF-1,
      tumor necrosis factor alpha (TNFalpha), and RANKL in RA synovial tissue was
      analyzed using confocal microscopy. After synovial fibroblasts and CD4+ T cells
      were treated with SDF-1, RANKL messenger RNA expression was determined by real
      time and reverse transcription polymerase chain reaction. Osteoclastogenesis was
      assessed by counting tartrate-resistant acid phosphatase-positive multinucleated
      cells in CD14+ monocytes cultured with SDF-1 in the presence of anticytokine
      antibodies or signal inhibitors and in monocytes cocultured with SDF-1-pretreated
      synovial fibroblasts and CD4+ T cells. RESULTS: RANKL, TNFalpha, and SDF-1 were
      coexpressed in the lining and sublining of RA synovium. SDF-1 stimulated RANKL
      expression in RA synovial fibroblasts and CD4+ T cells, and TNFalpha inhibition
      reduced this stimulation. When monocytes isolated from human peripheral blood
      were cultured with SDF-1, they were differentiated into osteoclasts in the
      absence of RANKL. Monocytes were also differentiated into osteoclasts when they
      were cocultured with SDF-1-pretreated synovial fibroblasts or CD4+T cells;
      however, this osteoclastogenesis was reduced by TNFalpha inhibition. CONCLUSION:
      Our findings indicate that SDF-1 induces osteoclastogenesis directly and
      indirectly via up-regulating RANKL expression in RA synovial fibroblasts and CD4+
      T cells, and that this is mediated by TNFalpha. The axis of SDF-1 and RANKL is a
      potential therapeutic target for RA-associated bone destruction.

PMID- 24574214
TI  - MicroRNA-451 down-regulates neutrophil chemotaxis via p38 MAPK.
AB  - OBJECTIVE: MicroRNAs (miRNAs) are endogenous small noncoding RNAs that regulate
      the activity of target messenger RNAs (mRNAs) and cellular processes. MicroRNA
      451 (miR-451) is one of the miRNAs that is conserved perfectly among vertebrates,
      and it regulates cell proliferation, invasion, and apoptosis in tumors. However,
      the role of miR-451 in autoimmune arthritis is unknown. This study was undertaken
      to identify the role of miR-451 in autoimmune arthritis. METHODS: We compared the
      expression of miR-451 in neutrophils from patients with rheumatoid arthritis (RA)
      and healthy controls. We also evaluated the role of miR-451 in neutrophil
      chemotaxis in vivo and in vitro using murine neutrophils. The regulation of p38
      MAPK by miR-451 was assessed. Double-stranded miR-451 was administered to SKG
      mice, the arthritis score was determined, and histologic examination was
      performed. RESULTS: MicroRNA-451 expression in neutrophils isolated from patients
      with RA was lower than that in healthy controls. Systemic administration of miR
      451 significantly disrupted the infiltration of neutrophils in an air-pouch model
      of local inflammation without affecting apoptosis of neutrophils. Overexpression
      of miR-451 significantly suppressed the migration of neutrophils to fMLP. We
      identified CPNE3 and Rab5a as direct targets of miR-451. Overexpression of miR
      451 suppressed the phosphorylation of p38 MAPK via 14-3-3zeta, a known target of
      miR-451, and Rab5a. In SKG mice, miR-451 treatment reduced the severity of
      arthritis and the number of infiltrating cells. CONCLUSION: These results suggest
      that miR-451 suppresses neutrophil chemotaxis via p38 MAPK and is a potential
      target in the treatment of RA.

PMID- 24574215
TI  - Thymidine phosphorylase regulates the expression of CXCL10 in rheumatoid
      arthritis fibroblast-like synoviocytes.
AB  - OBJECTIVE: Thymidine phosphorylase (TP) in rheumatoid arthritis (RA) fibroblast
      like synoviocytes (FLS) is induced by tumor necrosis factor alpha (TNFalpha) and
      other cytokines that have been reported to be major inflammation mediators in RA.
      We previously demonstrated that TP plays an important role in angiogenesis and
      tumor growth, invasion, and metastasis. The aim of this study was to investigate
      whether the role of TP in the pathogenesis of RA is similar to its role in
      tumors. METHODS: In FLS obtained from 2 patients with RA, the expression of TP,
      interferon-gamma (IFNgamma)-inducible protein 10 (CXCL10), and other cytokines
      was measured by quantitative real-time polymerase chain reaction, immunoblotting,
      and enzyme-linked immunosorbent assays. Microarray analysis was performed using
      FLS transfected with TYMP complementary DNA and treated with a TP inhibitor.
      RESULTS: The expression of TP in FLS was up-regulated by TNFalpha, interleukin
      1beta (IL-1beta), IL-17, IFNgamma, and lipopolysaccharide. Microarray analysis of
      FLS overexpressing TP identified CXCL10 as a thymidine phosphorylase-related
      gene. The expression of CXCL10 was induced by TNFalpha, and this induction was
      suppressed by TYMP small interfering RNA and TP inhibitor. Furthermore, the
      combination of TNFalpha and IFNgamma synergistically augmented the expression of
      TP and CXCL10. TP-induced CXCL10 expression was suppressed by the antioxidant EUK
      8. In the synovial tissue of patients with RA, TP levels were significantly
      correlated with CXCL10 expression. CONCLUSION: The combination of TNFalpha and
      IFNgamma strongly induced the expression of thymidine phosphorylase in RA FLS.
      The induction of thymidine phosphorylase enhanced the expression of CXCL10, which
      may contribute to the Th1 phenotype and bone destruction observed in RA.

PMID- 24574216
TI  - Gene associated with retinoid-interferon-induced mortality 19 attenuates murine
      autoimmune arthritis by regulation of th17 and treg cells.
AB  - OBJECTIVE: STAT-3 is a key transcriptional factor in the interleukin-6 (IL-6)
      mediated differentiation of Th17 cells. Because Th17 is believed to be a central
      player in rheumatoid arthritis (RA), we sought to evaluate whether an endogenous
      inhibitor of the STAT3 gene, GRIM-19 (gene associated with retinoid-interferon
      induced mortality 19), could attenuate the progression and severity of murine
      collagen-induced arthritis (CIA) through suppression of Th17 cells and,
      reciprocally, could increase expression of Treg cells. METHODS: Overexpression of
      GRIM-19 was produced either by intravenous/intramuscular administration of a GRIM
      19 overexpression vector in DBA1/J mice or by development of GRIM-19-transgenic
      (Tg) mice on a C57BL/6 background. Clinical signs were scored for arthritis
      severity, and mouse splenocytes, serum, and joint tissue were obtained for
      immunostaining and histologic analyses. RESULTS: The numbers of CD4+IL-17+ cells
      and CD4+pSTAT3+ cells were decreased, while the numbers of CD4+CD25+Foxp3+ cells
      and CD4+pSTAT5+ cells were increased, in both GRIM-19 vector-transfected and GRIM
      19-Tg mice. Administration of the GRIM-19 overexpression vector into mice with
      CIA markedly suppressed the clinical and histologic signs of arthritis in the
      affected joints. Similarly, when CIA was induced in GRIM-19-Tg mice, the
      arthritis phenotype was markedly attenuated and the expression of inflammatory
      cytokines (IL-1beta, IL-6, tumor necrosis factor alpha, and IL-17) in the
      arthritic joints was also significantly reduced. Moreover, bone marrow-derived
      monocyte/macrophages obtained from GRIM-19-Tg mice showed attenuated RANKL
      induced osteoclastogenesis in vitro. CONCLUSION: GRIM-19 improved the clinical
      and histologic features of CIA and also inhibited osteoclast formation. These
      findings suggest that GRIM-19 may be a novel treatment agent for RA.

PMID- 24574217
TI  - Hookworm-associated reactive spondyloarthritis.

PMID- 24574219
TI  - In vivo imaging of matrix metalloproteinase 12 and matrix metalloproteinase 13
      activities in the mouse model of collagen-induced arthritis.
AB  - OBJECTIVE: To develop enzyme-activatable Forster resonance energy transfer (FRET)
      substrate probes to detect matrix metalloproteinase 12 (MMP-12) and MMP-13
      activities in vivo in mouse models of inflammatory arthritis. METHODS: Peptidic
      FRET probes activated by MMP-12 and MMP-13 were reverse designed from inhibitors
      selected from a phosphinic peptide inhibitor library. Selectivity of the probes
      was demonstrated in vitro using MMP-1, MMP-2, MMP-3, MMP-12, and MMP-13. In vivo
      activation of the probes was tested in the zymosan-induced mouse model of
      inflammation, and probe specificity was evaluated by the MMP inhibitor GM6001 and
      specific synthetic inhibitors of MMP-12 and MMP-13. The probes were used to
      monitor these enzyme activities in the collagen-induced arthritis (CIA) model in
      vivo. RESULTS: The MMP-12 and MMP-13 activity probes (MMP12ap and MMP13ap,
      respectively) discriminated between the activities of the 2 enzymes. The in vivo
      activation of these probes was inhibited by GM6001 and by their respective
      specific inhibitors. In the CIA model, MMP12ap activation peaked 5 days after
      disease onset and showed strong correlation with disease severity during this
      time (r = 0.85, P < 0.0001). MMP13ap activation increased gradually after disease
      onset and correlated with disease severity over a longer period of 15 days (r =
      0.58, P < 0.0001). CONCLUSION: We generated two selective FRET probes that can be
      used to monitor MMP-12 and MMP-13 activities in live animals. MMP12ap follows the
      initial stage of inflammation in CIA, while MMP13ap follows the progression of
      the disease. The specificity of these probes is useful in monitoring the efficacy
      of MMP inhibitors.

PMID- 24574218
TI  - Pharmacologic repression of retinoic acid receptor-related orphan nuclear
      receptor gamma is therapeutic in the collagen-induced arthritis experimental
      model.
AB  - OBJECTIVE: The nuclear receptor retinoic acid receptor-related orphan nuclear
      receptor gamma (RORgamma; T cell-specific isoform RORgammat) is a key regulator
      of Th17 cell differentiation, controlling the production of the inflammatory
      cytokine interleukin-17 (IL-17). Lipopolysaccharide (LPS) stimulation of
      monocytes leads to the induction of RORgamma. We previously showed that the
      potent and selective inverse agonist of RORgamma, SR2211, was effective at
      suppressing IL-17 production in EL4 cells. The aim of this study was to examine
      the effects of SR2211 treatment on proinflammatory cytokine expression in LPS
      stimulated RAW 264.7 cells as well as on joint inflammation in vivo in mice with
      collagen-induced arthritis (CIA). METHODS: Collagen was injected into the tail of
      DBA mice, followed by a booster inoculation 21 days later. Three days prior to
      the booster inoculation, SR2211 was administered twice daily for 15 days. Thymus,
      spleen, and draining lymph nodes (DLNs) were then harvested, and Th17 cell
      differentiation and DLN stimulation were performed. RESULTS: Treatment of Th17
      cells with SR2211 suppressed the expression and production of inflammatory
      cytokines. Likewise, SR2211 reduced inflammatory cytokine production in LPS
      stimulated RAW 264.7 cells. Mice with CIA that received SR2211 twice daily for 15
      days exhibited a statistically significant reduction in joint inflammation as
      compared to mice that received only vehicle. Interestingly, systemic Th1 cell
      activation was detected in SR2211-treated mice with CIA, as indicated by an
      increase in interferon-gamma levels. CONCLUSION: The findings of this study
      support the idea of targeting RORgamma to therapeutically repress inflammatory T
      cell function and macrophage activation in humans with rheumatoid arthritis.
      Compounds such as SR2211 have potential utility for the treatment of inflammatory
      disease.

PMID- 24574220
TI  - Involvement of peripheral and spinal tumor necrosis factor alpha in spinal cord
      hyperexcitability during knee joint inflammation in rats.
AB  - OBJECTIVE: Tumor necrosis factor alpha (TNFalpha) is produced not only in
      peripheral tissues, but also in the spinal cord. The purpose of this study was to
      address the potential of peripheral and spinal TNFalpha to induce and maintain
      spinal hyperexcitability, which is a hallmark of pain states in the joints during
      rheumatoid arthritis and osteoarthritis. METHODS: In vivo recordings of the
      responses of spinal cord neurons to nociceptive knee input under normal
      conditions and in the presence of experimental knee joint inflammation were
      obtained in anesthetized rats. TNFalpha, etanercept, or antibodies to TNF
      receptors were applied to either the knee joint or the spinal cord surface.
      RESULTS: Injection of TNFalpha into the knee joint cavity increased the responses
      of spinal cord neurons to mechanical joint stimulation, and injection of
      etanercept into the knee joint reduced the inflammation-evoked spinal activity.
      These spinal effects closely mirrored the induction and reduction of peripheral
      sensitization. Responses to joint stimulation were also enhanced by spinal
      application of TNFalpha, and spinal application of either etanercept or anti-TNF
      receptor type I significantly attenuated the generation of inflammation-evoked
      spinal hyperexcitability, which is characterized by widespread pain sensitization
      beyond the inflamed joint. Spinally applied etanercept did not reduce established
      hyperexcitability in the acute kaolin/carrageenan model. In antigen-induced
      arthritis, etanercept decreased spinal responses on day 1, but not on day 3.
      CONCLUSION: While peripheral TNFalpha increases spinal responses to joint
      stimulation, spinal TNFalpha supports the generation of the full pattern of
      spinal hyperexcitability. However, established spinal hyperexcitability may be
      maintained by downstream mechanisms that are independent of spinal TNFalpha.

PMID- 24574222
TI  - Subscapular bursitis and calcinosis in a patient with dermatomyositis.

PMID- 24574221
TI  - A single functional group substitution in c5a breaks B cell and T cell tolerance
      and protects against experimental arthritis.
AB  - OBJECTIVE: A deficiency in C5 protects against arthritis development. However,
      there is currently no approach successfully translating these findings into
      arthritis therapy, as by targeting the key component, C5a. The aim of this study
      was to develop a vaccination strategy targeting C5a as therapy for patients with
      rheumatoid arthritis. METHODS: An anti-C5a vaccine was generated by incorporating
      the unnatural amino acid p-nitrophenylalanine (4NPA) into selected sites in the
      murine C5a molecule. C5a-4NPA variants were screened for their immunogenicity in
      mice on different arthritis-susceptible class II major histocompatibility complex
      (MHC) backgrounds. A candidate vaccine was tested for its impact on disease in a
      murine model of collagen-induced arthritis (CIA). Immunity toward endogenous C5a
      as well as type II collagen was monitored and characterized. RESULTS: Replacing a
      single tyrosine residue in position 35 (Y(35) ) with 4NPA allowed the generation
      of an anti-C5a vaccine, which partly protected mice against the development of
      CIA while strongly ameliorating the severity of clinical disease. Although
      differing in just 3 atoms from wild-type C5a (wtC5a), C5aY(35) 4NPA induced loss
      of T cell and B cell tolerance toward the endogenous protein in mice expressing
      class II MHC H-2(q) molecules. Despite differential B cell epitope recognition,
      antibodies induced by both wtC5a and C5aY(35) 4NPA neutralized C5a. Thus, anti
      wtC5a IgG titers during arthritis priming were potentially of critical importance
      for disease protection, because high titers of C5a-neutralizing antibodies after
      disease onset were unable to reverse the course of arthritis. CONCLUSION: The
      results of this study suggest that the most effective anti-C5a treatment in
      arthritis can be accomplished using a preventive vaccination strategy, and that
      treatment using conventional biologic or small molecule strategies targeting the
      C5a/C5aR axis may miss the optimal window for therapeutic intervention during the
      subclinical priming phase of the disease.

PMID- 24574223
TI  - Impact of exercise type and dose on pain and disability in knee osteoarthritis: a
      systematic review and meta-regression analysis of randomized controlled trials.
AB  - OBJECTIVE: To identify the optimal exercise program, characterized by type and
      intensity of exercise, length of program, duration of individual supervised
      sessions, and number of sessions per week, for reducing pain and patient-reported
      disability in knee osteoarthritis (OA). METHODS: A systematic review and meta
      analysis of randomized controlled trials were performed. Standardized mean
      differences (SMDs) were combined using a random-effects model. Study-level
      covariates were applied in meta-regression analyses in order to reduce between
      study heterogeneity. RESULTS: Forty-eight trials were included. Similar effects
      in reducing pain were found for aerobic, resistance, and performance exercise
      (SMD 0.67, 0.62, and 0.48, respectively; P = 0.733). These single-type exercise
      programs were more efficacious than programs that included different exercise
      types (SMD 0.61 versus 0.16; P < 0.001). The effect of aerobic exercise on pain
      relief increased with an increased number of supervised sessions (slope 0.022
      [95% confidence interval 0.002, 0.043]). More pain reduction occurred with
      quadriceps-specific exercise than with lower limb exercise (SMD 0.85 versus 0.39;
      P = 0.005) and when supervised exercise was performed at least 3 times a week
      (SMD 0.68 versus 0.41; P = 0.017). No impact of intensity, duration of individual
      sessions, or patient characteristics was found. Similar results were found for
      the effect on patient-reported disability. CONCLUSION: Optimal exercise programs
      for knee OA should have one aim and focus on improving aerobic capacity,
      quadriceps muscle strength, or lower extremity performance. For best results, the
      program should be supervised and carried out 3 times a week. Such programs have a
      similar effect regardless of patient characteristics, including radiographic
      severity and baseline pain.

PMID- 24574225
TI  - Gene expression analysis of murine and human osteoarthritis synovium reveals
      elevation of transforming growth factor beta-responsive genes in osteoarthritis
      related fibrosis.
AB  - OBJECTIVE: Synovial fibrosis is a major contributor to joint stiffness in
      osteoarthritis (OA). Transforming growth factor beta (TGFbeta), which is elevated
      in OA, plays a key role in the onset and persistence of synovial fibrosis.
      However, blocking of TGFbeta in OA as a therapeutic intervention for fibrosis is
      not an option since TGFbeta is crucial for cartilage maintenance and repair.
      Therefore, we undertook the present study to seek targets downstream of TGFbeta
      for preventing OA-related fibrosis without interfering with joint homeostasis.
      METHODS: Experiments were performed to determine whether genes involved in
      extracellular matrix turnover were responsive to TGFbeta and were elevated in OA
      related fibrosis. We analyzed gene expression in TGFbeta-stimulated human OA
      synovial fibroblasts and in the synovium of mice with TGFbeta-induced fibrosis,
      mice with experimental OA, and humans with end-stage OA. Gene expression was
      determined by microarray, low-density array, or quantitative polymerase chain
      reaction analysis. RESULTS: We observed an increase in expression of procollagen
      genes and genes encoding collagen crosslinking enzymes under all of the OA
      related fibrotic conditions investigated. Comparison of gene expression in
      TGFbeta-stimulated human OA synovial fibroblasts, synovium from mice with
      experimental OA, and synovium from humans with end-stage OA revealed that the
      genes PLOD2, LOX, COL1A1, COL5A1, and TIMP1 were up-regulated in all of these
      conditions. Additionally, we confirmed that these genes were up-regulated by
      TGFbeta in vivo in mice with TGFbeta-induced synovial fibrosis. CONCLUSION: Most
      of the up-regulated genes identified in this study would be poor targets for
      therapy development, due to their crucial functions in the joint. However, the
      highly up-regulated gene PLOD2, responsible for the formation of collagen
      crosslinks that make collagen less susceptible to enzymatic degradation, is an
      attractive and promising target for interference in OA-related synovial fibrosis.

PMID- 24574224
TI  - In vivo luminescence imaging of NF-kappaB activity and serum cytokine levels
      predict pain sensitivities in a rodent model of osteoarthritis.
AB  - OBJECTIVE: To investigate the relationship between NF-kappaB activity, cytokine
      levels, and pain sensitivities in a rodent model of osteoarthritis (OA). METHODS:
      OA was induced in transgenic NF-kappaB-luciferase reporter mice via
      intraarticular injection of monosodium iodoacetate (MIA). Using luminescence
      imaging we evaluated the temporal kinetics of NF-kappaB activity and its
      relationship to the development of pain sensitivities and serum cytokine levels
      in this model. RESULTS: MIA induced a transient increase in joint-related NF
      kappaB activity at early time points (day 3 after injection) and an associated
      biphasic pain response (mechanical allodynia). NF-kappaB activity, serum
      interleukin-6 (IL-6), IL-1beta, and IL-10 levels accounted for ~75% of the
      variability in pain-related mechanical sensitivities in this model. Specifically,
      NF-kappaB activity was strongly correlated with mechanical allodynia and serum IL
      6 levels in the inflammatory pain phase of this model (day 3), while serum IL
      1beta was strongly correlated with pain sensitivities in the chronic pain phase
      of the model (day 28). CONCLUSION: Our findings suggest that NF-kappaB activity,
      IL-6, and IL-1beta may play distinct roles in pain sensitivity development in
      this model of arthritis and may distinguish the acute pain phase from the chronic
      pain phase. This study establishes luminescence imaging of NF-kappaB activity as
      a novel imaging biomarker of pain sensitivities in this model of OA.

PMID- 24574226
TI  - Distribution and alteration of lymphatic vessels in knee joints of normal and
      osteoarthritic mice.
AB  - OBJECTIVE: To investigate the distribution and alteration of lymphatic vessels
      and draining function in knee joints of normal and osteoarthritic mice. METHODS:
      For the mouse models of osteoarthritis (OA), we used mice with meniscal
      ligamentous injury or mice with conditional knockout of the gene for cartilage
      transforming growth factor beta (TGFbeta) type II receptor. The severity of
      cartilage loss and joint destruction was assessed histologically. Capillary and
      mature lymphatic vessels were identified and analyzed using double
      immunofluorescence staining and a whole-slide digital imaging system. Lymphatic
      drainage of knee joints was examined using near-infrared lymphatic imaging.
      Patient joint specimens obtained during total knee or hip arthroplasty were
      evaluated to verify the content validity of the mouse findings. RESULTS:
      Lymphatic vessels were distributed in soft tissues (mainly around the joint
      capsule, ligaments, fat pads, and muscles of normal knees). The number of
      lymphatic vessels, particularly the number of capillaries, was significantly
      increased in joints of mice with mild OA, while the number of mature lymphatic
      vessels was markedly decreased in joints of mice with severe OA. OA knees
      exhibited significantly decreased lymph clearance. The number of both capillary
      and mature lymphatic vessels was significantly decreased in the joints of
      patients with OA. CONCLUSION: The whole-slide digital imaging system is a
      powerful tool, enabling the identification and assessment of lymphatic
      microvasculature in the entire mouse knee. Lymphatic capillaries and mature
      vessels are present in various soft tissues around articular spaces.
      Abnormalities of lymphatic vessels and draining function, including significantly
      reduced numbers of mature vessels and impaired clearance, are present in OA
      joints.

PMID- 24574227
TI  - Spinal inflammation in the absence of sacroiliac joint inflammation on magnetic
      resonance imaging in patients with active nonradiographic axial
      spondyloarthritis.
AB  - OBJECTIVE: To evaluate the presence of spinal inflammation with and without
      sacroiliac (SI) joint inflammation on magnetic resonance imaging (MRI) in
      patients with active nonradiographic axial spondyloarthritis (SpA), and to
      compare the disease characteristics of these subgroups. METHODS: ABILITY-1 is a
      multicenter, randomized, controlled trial of adalimumab versus placebo in
      patients with nonradiographic axial SpA classified using the Assessment of
      SpondyloArthritis international Society axial SpA criteria. Baseline MRIs were
      centrally scored independently by 2 readers using the Spondyloarthritis Research
      Consortium of Canada (SPARCC) method for the SI joints and the SPARCC 6
      discovertebral unit method for the spine. Positive evidence of inflammation on
      MRI was defined as a SPARCC score of >=2 for either the SI joints or the spine.
      RESULTS: Among patients with baseline SPARCC scores, 40% had an SI joint score of
      >=2 and 52% had a spine score of >=2. Forty-nine percent of patients with
      baseline SI joint scores of <2, and 58% of those with baseline SI joint scores of
      >=2, had a spine score of >=2. Comparison of baseline disease characteristics by
      baseline SI joint and spine scores showed that a greater proportion of patients
      in the subgroup with a baseline SPARCC score of >=2 for both SI joints and spine
      were male, and patients with spine and SI joint scores of <2 were younger and had
      shorter symptom duration. SPARCC spine scores correlated with baseline symptom
      duration, and SI joint scores correlated negatively with the baseline Bath
      Ankylosing Spondylitis Disease Activity Index, but neither correlated with the
      baseline Ankylosing Spondylitis Disease Activity Score, total back pain, the
      patient's global assessment of disease activity, the Bath Ankylosing Spondylitis
      Functional Index, morning stiffness, nocturnal pain, or C-reactive protein level.
      CONCLUSION: Assessment by experienced readers showed that spinal inflammation on
      MRI might be observed in half of patients with nonradiographic axial SpA without
      SI joint inflammation.

PMID- 24574228
TI  - Laquinimod delays and suppresses nephritis in lupus-prone mice and affects both
      myeloid and lymphoid immune cells.
AB  - OBJECTIVE: Lupus nephritis depends on autoantibody deposition and activation of
      multiple immune cell types that promote kidney inflammation, including
      lymphocytes and monocyte/macrophages. Laquinimod, currently in clinical trials
      for multiple sclerosis and lupus nephritis, reduces infiltration of inflammatory
      cells into the spinal cord in experimental autoimmune encephalomyelitis.
      Activated monocyte/macrophages infiltrate the kidneys during nephritis in
      systemic lupus erythematosus (SLE). We undertook this study to determine whether
      using laquinimod to reduce monocyte/macrophage-driven tissue damage as well as to
      alter lymphocytes in SLE nephritis could have greater therapeutic benefit than
      current treatments that primarily affect lymphocytes, such as mycophenolate
      mofetil (MMF). METHODS: To test laquinimod efficacy, we used the (NZB * NZW)F1
      mouse model of SLE, in which disease manifests as nephritis. Preventive and
      therapeutic studies were performed to determine whether laquinimod could prevent
      or delay nephritis, as measured by proteinuria, serum creatinine, survival, and
      renal pathology. Spleen and kidney leukocyte populations and suppression assays
      were analyzed by flow cytometry. RESULTS: Laquinimod prevented or delayed lupus
      manifestations at levels equal to or better than MMF. Laquinimod treatment was
      associated with reduced numbers of monocyte/macrophages, dendritic cells, and
      lymphocytes, as well as with induction of myeloid-derived suppressor cells in
      spleens and kidneys. Laquinimod suppressed macrophage-secreted tumor necrosis
      factor alpha and induced production of interleukin-10 (IL-10). In addition,
      laquinimod suppressed interferon-gamma and IL-17 production by lymphocytes and
      down-regulated expression of activation/costimulatory markers on antigen
      presenting cells. CONCLUSION: The effects of laquinimod on myeloid and lymphoid
      cells may contribute to improvements in (NZB * NZW)F1 mouse survival,
      proteinuria, and glomerulonephritis. Future development of laquinimod as a
      therapeutic agent for lupus nephritis is promising.

PMID- 24574229
TI  - Cooperation of factor VII-activating protease and serum DNase I in the release of
      nucleosomes from necrotic cells.
AB  - OBJECTIVE: Removal of dead cells is essential in the maintenance of tissue
      homeostasis, and efficient removal prevents exposure of intracellular content to
      the immune system, which could lead to autoimmunity. The plasma protease factor
      VII-activating protease (FSAP) can release nucleosomes from late apoptotic cells.
      FSAP circulates as an inactive single-chain protein, which is activated upon
      contact with either apoptotic cells or necrotic cells. The purpose of this study
      was to investigate the role of FSAP in the release of nucleosomes from necrotic
      cells. METHODS: Necrotic Jurkat cells were incubated with serum, purified 2-chain
      FSAP, and/or DNase I. Nucleosome release was analyzed by flow cytometry, and
      agarose gel electrophoresis was performed to detect DNA breakdown. RESULTS:
      Incubation with serum released nucleosomes from necrotic cells. Incubation with
      FSAP-deficient serum or serum in which FSAP was inhibited by a blocking antibody
      was unable to release nucleosomes from necrotic cells, confirming that FSAP is
      indeed the essential serum factor in this process. Together with serum DNase I,
      FSAP induced the release of DNA from the cells, the appearance of nucleosomes in
      the supernatant, and the fragmentation of chromatin into eventually
      mononucleosomes. CONCLUSION: FSAP and DNase I are the essential serum factors
      that cooperate in necrotic cell DNA degradation and nucleosome release. We
      propose that this mechanism may be important in the removal of potential
      autoantigens.

PMID- 24574230
TI  - Epicutaneous application of toll-like receptor 7 agonists leads to systemic
      autoimmunity in wild-type mice: a new model of systemic Lupus erythematosus.
AB  - OBJECTIVE: To examine whether topical treatment of wild-type mice with Toll-like
      receptor 7 (TLR-7) agonists leads to lupus-like autoimmunity. METHODS: Wild-type
      FVB/N, BALB/c, and C57BL/6 mice were treated with the topical TLR-7 agonist
      imiquimod or R848 administered to the ear 3 times weekly. During treatment, the
      mice were monitored for serum autoantibody and creatinine levels as well as
      histopathology of the kidneys, spleens, livers, hearts, and skin. Immunologic
      abnormalities were analyzed by immunohistochemistry, quantitative reverse
      transcription-polymerase chain reaction, and fluorescence-activated cell sorting.
      The role of plasmacytoid dendritic cells (PDCs) in the development of autoimmune
      disease was validated by in vivo treatment with an anti-PDC antibody. Diseased
      mice underwent ultraviolet B irradiation, to evaluate skin photosensitivity. The
      disease-causing effect of topical application of imiquimod was compared with that
      of systemic (intraperitoneal) administration. TLR-7- and TLR-9-deficient mice
      were used to validate the role of TLR-7. RESULTS: Wild-type mice of different
      genetic backgrounds developed systemic autoimmune disease following 4 weeks of
      topical treatment with imiquimod or R848, with elevated levels of autoantibodies
      to double-stranded DNA and multiple organ involvement, including
      glomerulonephritis, hepatitis, carditis, and photosensitivity. Expression of Ifna
      and Mx1, the interferon-alpha-stimulated gene, was up-regulated in the organs of
      imiquimod-treated mice. However, disease caused by intraperitoneal injection of
      imiquimod was less severe than that induced by topical application. In vivo
      depletion of PDCs by a specific antibody protected mice against the autoimmunity
      induced by topical administration of imiquimod, suggesting a role of PDCs.
      Furthermore, TLR-7-deficient mice, but not TLR-9-deficient mice, were protected
      against autoimmunity. CONCLUSION: This protocol provides a novel model of
      inducible systemic lupus erythematosus in wild-type mice and underscores the skin
      as the primary organ that allows TLR-7 agonists to induce SLE.

PMID- 24574231
TI  - Skin progenitor cells contribute to bleomycin-induced skin fibrosis.
AB  - OBJECTIVE: The origin of the cells that contribute to skin fibrosis is unclear.
      We undertook the present study to assess the contribution of Sox2-expressing skin
      progenitor cells to bleomycin-induced scleroderma. METHODS: Scleroderma was
      induced, by bleomycin administration, in wild-type mice and in mice in which CCN2
      was deleted from Sox2-expressing cells. Lineage tracing analysis was performed to
      assess whether cells expressing Sox2 are recruited to fibrotic lesions in
      response to bleomycin-induced scleroderma. RESULTS: In response to bleomycin,
      Sox2-positive/alpha-smooth muscle actin-positive cells were recruited to fibrotic
      tissue. CCN2-conditional knockout mice in which CCN2 was deleted from Sox2
      expressing cells exhibited resistance to bleomycin-induced skin fibrosis.
      Collectively, these results indicate that CCN2 is required for the recruitment of
      progenitor cells and that CCN2-expressing progenitor cells are essential for
      bleomycin-induced skin fibrosis. Lineage tracing analysis using mice in which a
      tamoxifen-dependent Cre recombinase was expressed under the control of the Sox2
      promoter confirmed that progenitor cells were recruited to the fibrotic lesion in
      response to bleomycin, and that this did not occur in CCN2-knockout mice. The
      ability of serum to induce alpha-smooth muscle actin expression in skin
      progenitor cells required the presence of CCN2. CONCLUSION: Sox2-positive skin
      progenitor cells are required in order for bleomycin-induced skin fibrosis to
      occur, and CCN2 is required for the recruitment of these cells to the fibrotic
      lesion. Targeting stem cell recruitment or CCN2 may therefore represent a useful
      therapeutic approach in combating fibrotic skin disease.

PMID- 24574233
TI  - Brief report: lysyl oxidase is a potential biomarker of fibrosis in systemic
      sclerosis.
AB  - OBJECTIVE: Fibrosis is a major cause of morbidity and mortality in systemic
      sclerosis (SSc). Levels of lysyl oxidase (LOX), an extracellular enzyme that
      stabilizes collagen fibrils, have been found to be elevated in the skin of SSc
      patients, but have not been evaluated in the serum or correlated with the
      clinical parameters. We undertook this study to evaluate serum LOX levels in SSc
      patients and to correlate these levels with clinical parameters of SSc. METHODS:
      SSc patients were evaluated for demographic features, clinical manifestations,
      routine laboratory tests, serum autoantibodies, serum LOX concentrations, and
      nailfold capillaroscopy patterns. They underwent pulmonary function testing,
      echocardiography, and high-resolution computed tomography scans of the lung,
      assessment of skin fibrosis by the modified Rodnan skin thickness score (MRSS),
      and assessment of disease severity and activity by the Medsger severity scale and
      the Valentini activity index. RESULTS: Twenty-six SSc patients were evaluated and
      compared with 25 healthy controls and with 9 disease control patients with
      primary myelofibrosis. Almost 62% of the SSc patients (16 of 26) had limited
      cutaneous SSc (lcSSc), while 38% had diffuse cutaneous SSc (dcSSc) (10 of 26);
      31% of the patients (8 of 26) had lung involvement. The LOX concentration in SSc
      patients was higher than that in healthy controls and similar to that in disease
      controls (P < 0.0001), and it was significantly higher in patients with dcSSc
      than in those with lcSSc (P = 0.006). The LOX concentration correlated with the
      MRSS in patients without lung fibrosis. CONCLUSION: This study is the first to
      demonstrate high serum LOX levels in SSc patients that correlate specifically
      with skin fibrosis. These correlations suggest that LOX levels may serve as a
      novel biomarker of fibrosis. Future studies are warranted to determine whether
      LOX is a potential therapeutic target in SSc.

PMID- 24574232
TI  - Association of Interferon- and transforming growth factor beta-regulated genes
      and macrophage activation with systemic sclerosis-related progressive lung
      fibrosis.
AB  - OBJECTIVE: Systemic sclerosis (SSc)-related interstitial lung disease (ILD) is
      one of the leading causes of mortality. We undertook this study to analyze the
      gene expression of lung tissue in a prospective cohort of patients with SSc
      related ILD and to compare it with that in control lungs and with 2 prospective
      clinical parameters in order to understand the molecular pathways implicated in
      progressive lung disease. METHODS: Lung tissue was obtained by open lung biopsy
      in 28 consecutive patients with SSc-related ILD and in 4 controls. High
      resolution computed tomography (HRCT) and pulmonary function testing (PFT) were
      performed at baseline and 2-3 years after treatment based on lung histologic
      classification. Microarray analysis was performed, and the results were
      correlated with changes in the HRCT score (FibMax) and PFT values. Quantitative
      polymerase chain reaction (qPCR) and immunohistochemistry were used to confirm
      differential levels of messenger RNA and protein. RESULTS: Lung microarray data
      distinguished patients with SSc-related ILD from healthy controls. In the lungs
      of patients with SSc-related ILD who had nonspecific interstitial pneumonia
      (NSIP), expressed genes included macrophage markers, chemokines, collagen, and
      transforming growth factor beta (TGFbeta)- and interferon (IFN)-regulated genes.
      Expression of these genes correlated with progressive lung fibrosis defined by
      the change in FibMax. Immunohistochemistry confirmed increased markers of
      collagen (COL1A1), IFN (OAS1 and IFI44), and macrophages (CCL18 and CD163), and
      the positive correlation with the change in FibMax was confirmed by qPCR in a
      larger group of SSc patients with NSIP. Several genes correlated with both the
      change in FibMax (r > 0.4) and the change in % predicted forced vital capacity (r
      < -0.1), including IFN and macrophage markers, chemokines, and heat-shock
      proteins. CONCLUSION: These results highlight major pathogenic pathways relevant
      to progressive pulmonary fibrosis in SSc-related ILD: macrophage emigration and
      activation, and up-regulated expression of TGFbeta- and IFN-regulated genes.

PMID- 24574234
TI  - Genome-wide DNA methylation patterns in naive CD4+ T cells from patients with
      primary Sjogren's syndrome.
AB  - OBJECTIVE: Primary Sjogren's syndrome (SS) is a systemic autoimmune disease with
      incompletely understood etiology. This study was undertaken to investigate the
      role of epigenetic dysregulation in the pathogenesis of primary SS. METHODS: A
      genome-wide DNA methylation study was performed in naive CD4+ T cells from 11
      patients with primary SS compared to age-, sex-, and ethnicity-matched healthy
      controls. Cytosine methylation was quantified using the Illumina Infinium
      HumanMethylation450 BeadChip array, and the data were validated using bisulfite
      sequencing. RESULTS: Genome-wide analyses identified 553 hypomethylated CpG sites
      and 200 hypermethylated CpG sites in naive CD4+ T cells from patients with
      primary SS as compared to healthy controls, representing 311 hypomethylated and
      115 hypermethylated gene regions. The hypomethylated genes in patients with
      primary SS included LTA (encoding lymphotoxin alpha). Other relevant genes, such
      as CD247, TNFRSF25, PTPRC, GSTM1, and PDCD1, were also hypomethylated. The
      interferon signature pathway was represented by hypomethylation of STAT1, IFI44L,
      USP18, and IFITM1. A group of genes encoding members of the solute carrier
      proteins were differentially methylated. In addition, the transcription factor
      gene RUNX1 was hypermethylated in patients with primary SS, suggesting a possible
      connection to lymphoma predisposition. Gene ontology (GO) analysis of
      hypomethylated genes demonstrated enrichment of genes involved in lymphocyte
      activation and immune response. GO terms for hypermethylated genes included
      antigen processing and presentation. CONCLUSION: This is the first epigenome-wide
      DNA methylation study in patients with primary SS. These findings highlight a
      role for DNA methylation in primary SS and identify disease-associated DNA
      methylation changes in several genes and pathways in naive CD4+ T cells from
      patients with primary SS that may be involved in the pathogenesis of this
      disease.

PMID- 24574236
TI  - Distinct phenotype clusters in childhood inflammatory brain diseases:
      implications for diagnostic evaluation.
AB  - OBJECTIVE: To identify distinct clusters of children with inflammatory brain
      diseases based on clinical, laboratory, and imaging features at presentation, to
      assess which features contribute strongly to the development of clusters, and to
      compare additional features between the identified clusters. METHODS: A single
      center cohort study was performed with children who had been diagnosed as having
      an inflammatory brain disease between June 1, 1989 and December 31, 2010.
      Demographic, clinical, laboratory, neuroimaging, and histologic data at diagnosis
      were collected. K-means cluster analysis was performed to identify clusters of
      patients based on their presenting features. Associations between the clusters
      and patient variables, such as diagnoses, were determined. RESULTS: A total of
      147 children (50% female; median age 8.8 years) were identified: 105 with primary
      central nervous system (CNS) vasculitis, 11 with secondary CNS vasculitis, 8 with
      neuronal antibody syndromes, 6 with postinfectious syndromes, and 17 with other
      inflammatory brain diseases. Three distinct clusters were identified. Paresis and
      speech deficits were the most common presenting features in cluster 1. Children
      in cluster 2 were likely to present with behavior changes, cognitive dysfunction,
      and seizures, while those in cluster 3 experienced ataxia, vision abnormalities,
      and seizures. Lesions seen on T2/fluid-attenuated inversion recovery sequences of
      magnetic resonance imaging were common in all clusters, but unilateral ischemic
      lesions were more prominent in cluster 1. The clusters were associated with
      specific diagnoses and diagnostic test results. CONCLUSION: Children with
      inflammatory brain diseases presented with distinct phenotypical patterns that
      are associated with specific diagnoses. This information may inform the
      development of a diagnostic classification of childhood inflammatory brain
      diseases and suggest that specific pathways of diagnostic evaluation are
      warranted.

PMID- 24574235
TI  - Predictors of clinical improvement in rituximab-treated refractory adult and
      juvenile dermatomyositis and adult polymyositis.
AB  - OBJECTIVE: To identify the clinical and laboratory predictors of clinical
      improvement in a cohort of myositis patients treated with rituximab. METHODS: We
      analyzed data for 195 patients with myositis (75 with adult polymyositis [PM], 72
      with adult dermatomyositis [DM], and 48 with juvenile DM) in the Rituximab in
      Myositis trial. Clinical improvement was defined as 20% improvement in at least 3
      of the following 6 core set measures of disease activity: physician's and
      patient's/parent's global assessment of disease activity, manual muscle testing,
      physical function, muscle enzymes, and extramuscular disease activity. We
      analyzed the association of the following baseline variables with improvement:
      myositis clinical subgroup, demographics, myositis damage, clinical and
      laboratory parameters, core set measures, rituximab treatment, and myositis
      autoantibodies (antisynthetase, anti-Mi-2, anti-signal recognition particle, anti
      transcription intermediary factor 1gamma [TIF-1gamma], anti-MJ, other
      autoantibodies, and no autoantibodies). All measures were univariately assessed
      for association with improvement using time-to-event analyses. A multivariable
      time-dependent proportional hazards model was used to evaluate the association of
      individual predictive factors with improvement. RESULTS: In the final
      multivariable model, the presence of an antisynthetase, primarily anti-Jo-1
      (hazard ratio [HR] 3.08, P < 0.01), anti-Mi-2 (HR 2.5, P < 0.01), or other
      autoantibody (HR 1.4, P = 0.14) predicted a shorter time to improvement compared
      to the absence of autoantibodies. A lower physician's global assessment of damage
      (HR 2.32, P = 0.02) and juvenile DM (versus adult myositis) (HR 2.45, P = 0.01)
      also predicted improvement. Unlike autoantibody status, the predictive effect of
      physician's global assessment of damage and juvenile DM diminished by week 20.
      Rituximab treatment did not affect these associations. CONCLUSION: Our findings
      indicate that the presence of antisynthetase and anti-Mi-2 autoantibodies,
      juvenile DM subset, and lower disease damage strongly predict clinical
      improvement in patients with refractory myositis.

PMID- 24574239
TI  - Drug-associated polymyalgia rheumatica/giant cell arteritis occurring in two
      patients after treatment with ipilimumab, an antagonist of ctla-4.

PMID- 24574238
TI  - Predictors of new-onset widespread pain in older adults: results from a
      population-based prospective cohort study in the UK.
AB  - OBJECTIVE: In older adults, widespread pain (WP) is common, although its etiology
      is unclear. This study sought to identify factors associated with an increased
      risk of developing WP in adults age >=50 years. METHODS: A population-based
      prospective study was conducted. A baseline questionnaire was administered to
      subjects to collect data on pain, psychological status, lifestyle and health
      behaviors, and sociodemographic and clinical factors. Participants free of WP (as
      defined by the American College of Rheumatology 1990 criteria for fibromyalgia)
      were followed up for 3 years, and those with new-onset WP at followup were
      identified. Logistic regression analyses were used to test the relationship
      between baseline factors and new-onset WP. Multiple imputation was used to test
      the results for sensitivity to missing data. RESULTS: In this population-based
      study, 4,326 subjects (1,562 reporting no pain at baseline and 2,764 reporting
      some pain at baseline) participated at followup. Of these participants, 800
      (18.5%) reported a status of new WP at followup (of whom, 121 [7.7%] had reported
      no pain at baseline and 679 [24.6%] had reported some pain at baseline). The
      majority of the study factors were associated with new-onset WP. However, only a
      few factors showed a persistent association with new-onset WP in the multivariate
      analysis, including age (odds ratio [OR] 0.97, 95% confidence interval [95% CI]
      0.96-0.99), baseline pain status (OR 1.1, 95% CI 1.08-1.2), anxiety (OR 1.5, 95%
      CI 1.01-2.1), physical health-related quality of life (OR 1.3, 95% CI 1.1-1.5),
      cognitive complaint (OR 1.3, 95% CI 1.04-1.6), and nonrestorative sleep (OR 1.9,
      95% CI 1.2-2.8). These associations persisted after adjustment for the presence
      of diffuse osteoarthritis (OA), which led to a modest increase in model fit (C
      statistic 0.738, compared with 0.731 in the model excluding diffuse OA). The
      results were not sensitive to missing data. CONCLUSION: Of the factors measured
      in this study, nonrestorative sleep was the strongest independent predictor of
      new-onset WP.

PMID- 24574240
TI  - Reply: To PMID 23728826.

PMID- 24574241
TI  - Determining adherence to therapeutic regimens in patients with chronic illness:
      comment on the article by Waimann et Al.

PMID- 24574244
TI  - In situ total X-ray scattering study of WO3 nanoparticle formation under
      hydrothermal conditions.
AB  - Pair distribution function analysis of in situ total scattering data recorded
      during formation of WO3 nanocrystals under hydrothermal conditions reveal that a
      complex precursor structure exists in solution. The WO6 polyhedra of the
      precursor cluster undergo reorientation before forming the nanocrystal. This
      reorientation is the critical element in the formation of different hexagonal
      polymporphs of WO3.

PMID- 24574245
TI  - Biomimetic nanocomposites to control osteogenic differentiation of human
      mesenchymal stem cells.
AB  - The design of biomimetic nanomaterials that can directly influence the behavior
      of cells and facilitate the regeneration of tissues and organs has become an
      active area of research. Here, the production of materials based on nano
      hydroxyapatite composites in scaffolds with nanofibrous and nanoporous
      topographies, designed to mimic the native bone matrix for applications in bone
      tissue engineering, is reported. Human mesenchymal stem cells grown on these
      nanocomposites are stimulated to rapidly produce bone minerals in situ, even in
      the absence of osteogenic supplements in the cell-culture medium. Nanocomposites
      comprising type I collagen and nano-hydroxyapatite are found to be especially
      efficient at inducing mineralization. When subcutaneously implanted into nude
      mice, this biomimetic nanocomposite is able to form a new bone matrix within only
      two weeks. Furthermore, when the nanocomposite is enriched with human mesenchymal
      stem cells before implantation, development of the bone matrix is accelerated to
      within one week. To the best of the authors' knowledge, this study provides the
      first clear in vitro and in vivo demonstration of osteoinduction controlled by
      the material characteristics of a biomimetic nanocomposite. This approach can
      potentially facilitate the translation of de novo bone-formation technologies to
      the clinic.

PMID- 24574246
TI  - Anti-dengue-virus activity and structure-activity relationship studies of
      lycorine derivatives.
AB  - Dengue is a systemic viral infection that is transmitted to humans by Aedes
      mosquitoes. No vaccines or specific therapeutics are currently available for
      dengue. Lycorine, which is a natural plant alkaloid, has been shown to possess
      antiviral activities against flaviviruses. In this study, a series of novel
      lycorine derivatives were synthesized and assayed for their inhibition of dengue
      virus (DENV) in cell cultures. Among the lycorine analogues, 1-acetyllycorine
      exhibited the most potent anti-DENV activity (EC50 =0.4 MUM) with a reduced
      cytotoxicity (CC50 >300 MUM), which resulted in a selectivity index (CC50 /EC50 )
      of more than 750. The ketones 1-acetyl-2-oxolycorine (EC50 =1.8 MUM) and 2
      oxolycorine (EC50 =0.5 MUM) also exhibited excellent antiviral activities with
      low cytotoxicity. Structure-activity relationships for the lycorine derivatives
      against DENV are discussed. A three-dimensional quantitative structure-activity
      relationship model was established by using a comparative molecular-field
      analysis protocol in order to rationalize the experimental results. Further
      modifications of the hydroxy group at the C1 position with retention of a ketone
      at the C2 position could potentially lead to inhibitors with improved overall
      properties. 

PMID- 24574248
TI  - A meshless point collocation treatment of transient bioheat problems.
AB  - A meshless numerical method is proposed for the solution of the transient bioheat
      equation in two and three dimensions. The Pennes bioheat equation is extended in
      order to incorporate water evaporation, tissue damage, and temperature-dependent
      tissue properties during tumor ablation. The conductivity of the tissue is not
      assumed constant but is treated as a local function to simulate local variability
      due to the existence of usually unclear interfacing of healthy and pathological
      segments. In this way, one avoids the need for accurate identification of the
      boundaries between pathological and healthy regions, which is a typical problem
      in medical practice, and sidesteps, evidently, the corresponding mathematical
      treatment of such boundaries, which is usually a tedious procedure with some
      inevitable degree of approximation. The numerical results of the new method for
      test applications of the bioheat transfer equation are validated against
      analytical predictions and predictions of other numerical methods. 3D simulations
      are presented that involve the modeling of tumor ablation and account for
      metabolic heat generation, blood perfusion, and heat ablation using realistic
      values for the various parameters. An evaluation of the effective medium
      approximation to homogenize conductivity fields for use with the bioheat equation
      is also provided.

PMID- 24574247
TI  - Investigation of maternal genotype effects in autism by genome-wide association.
AB  - Like most psychiatric disorders, autism spectrum disorders have both a genetic
      and an environmental component. While previous studies have clearly demonstrated
      the contribution of in utero (prenatal) environment on autism risk, most of them
      focused on transient environmental factors. Based on a recent sibling study, we
      hypothesized that environmental factors could also come from the maternal genome,
      which would result in persistent effects across siblings. In this study, the
      possibility of maternal genotype effects was examined by looking for common
      variants (single-nucleotide polymorphisms or SNPs) in the maternal genome
      associated with increased risk of autism in children. A case/control genome-wide
      association study was performed using mothers of probands as cases, and either
      fathers of probands or normal females as controls. Autism Genetic Resource
      Exchange and Illumina Genotype Control Database were used as our discovery cohort
      (n = 1616). The same analysis was then replicated on Simon Simplex Collection and
      Study of Addiction: Genetics and Environment datasets (n = 2732). We did not
      identify any SNP that reached genome-wide significance (P < 10(-8) ), and thus a
      common variant of large effect is unlikely. However, there was evidence for the
      possibility of a large number of alleles of effective size marginally below our
      power to detect.

PMID- 24574249
TI  - Production of crude cellulase and xylanase from Trichoderma harzianum PPDDN10
      NFCCI-2925 and its application in photocopier waste paper recycling.
AB  - This paper implies production of cellulase and xylanase enzyme using a potent
      strain of Trichoderma harzianum for the efficient deinking of photocopier waste
      papers. Different nutritional and environmental factors were optimized for higher
      production of cellulase along with xylanase. After fermentation, maximum enzyme
      extraction was achieved from fermented matter using a three-step extraction
      process with increased efficiency by 26.6-29.3 % over single-step extraction.
      Static solid state was found as the best fermentation type using wheat bran (WB)
      as carbon source and ammonium ferrous sulfate (0.02 M) as nitrogen source.
      Subsequently, inoculum size (8 * 10(6) CFU/gds), incubation days (4 days),
      temperature (34  degrees C), initial pH (6.0), and moisture ratio (1:3)
      significantly affected the enzyme production. Cellulase and xylanase activities
      were found to be maximum at pH 5.5 and temperature 55-60  degrees C with good
      stability (even up to 6 h). Furthermore, this crude enzyme was evaluated for the
      deinking of photocopier waste papers without affecting the strength properties
      with improved drainage as an additional advantage. The crude enzyme-deinked pulp
      showed 23.6 % higher deinking efficiency and 3.2 % higher brightness than
      chemically deinked pulp. Strength properties like tensile, burst indices, and
      folding endurance were also observed to improve by 6.7, 13.4, and 10.3 %,
      respectively, for enzyme-deinked pulp. However, the tear index was decreased by
      10.5 %. The freeness of the pulp was also increased by 21.6 % with reduced
      drainage time by 13.9 %.

PMID- 24574250
TI  - Impact of targeted specific antibiotic delivery for gut microbiota modulation on
      high-fructose-fed rats.
AB  - The objective of present investigation was to study the effect of gut microbiota
      alteration by oral administration of targeted delivery of pH sensitive cefdinir
      microspheres to high-fructose-fed (HFD) rats. Rats were fed with a high-fructose
      diet with or without cefdinir microsphere administration for 30 days. The fecal
      microbiota community, oral glucose tolerance, the markers of liver injury, plasma
      and hepatic lipids profile, and histological evaluation were investigated. The
      levels of blood glucose, liver injury markers, lipid profile in plasma and liver,
      and fat tissue were significantly increased in high-fructose-fed rats. However,
      after pH-sensitive cefdinir microsphere administration, the elevation of these
      parameters was significantly suppressed. Cef EL significantly lowered the
      increased AST (p < 0.05) and ALT (p < 0.001) levels in HFD group. There is a
      significant lower (p < 0.01) AUCglucose level in Cef EL group than HFD group The
      histological changes in the liver and the small and large intestines were more
      profound in HFD group as compared to cefdinir-treated HFD and control groups.
      Feeding of cefdinir microsphere sustained lactobacilli and bifidobacteria and
      significantly decreased (p < 0.05) the number of Enterobacteriaceae induced by
      HFD. Experimental evidences demonstrated that the effectiveness of pH-specific
      cefdinir microsphere on reducing insulin resistance and development of metabolic
      changes in high-fructose-fed rats and suggested that it may be a promising
      therapeutic agent in treating type 2 diabetes. Intestinal-targeted antibiotic
      delivery needs to be further explored for its therapeutic applications.

PMID- 24574251
TI  - Stabilization studies on bacterially produced human paraoxonase 1 for improving
      its shelf life.
AB  - Human paraoxonase 1 (h-PON1) is a ~40 kDa multi-tasking enzyme that plays a major
      role in determining individual susceptibility towards various disease conditions.
      It is a strong candidate for the development of therapeutic intervention for
      various diseases and other conditions in humans. However, purified h-PON1 is
      unstable and there is a need to find condition(s) that can increase the shelf
      life of the enzyme. In this report, we present the results of our investigation
      on the effect of excipients on the stability of bacterially produced human PON1
      when stored under different storage conditions. Our results show that (a) glycine
      and serine are most effective in stabilizing the enzyme when stored in aqueous
      buffer at 25  degrees C for 30 days, and (b) trehalose, maltose, and BSA exerted
      maximum stabilization effect when the enzyme was stored in freeze-dried form at
      25  degrees C for 60 days. Results of this study can be used to increase the
      shelf life of purified h-PON1 enzyme.

PMID- 24574252
TI  - ESC Working Group on Myocardial Function Position Paper: how to study the right
      ventricle in experimental models.
AB  - The right ventricle has become an increasing focus in cardiovascular research. In
      this position paper, we give a brief overview of the specific pathophysiological
      features of the right ventricle, with particular emphasis on functional and
      molecular modifications as well as therapeutic strategies in chronic overload,
      highlighting the differences from the left ventricle. Importantly, we put
      together recommendations on promising topics of research in the field,
      experimental study design, and functional evaluation of the right ventricle in
      experimental models, from non-invasive methodologies to haemodynamic evaluation
      and ex vivo set-ups. 

PMID- 24574253
TI  - Constitutive expression of vascular endothelial cell growth factor (VEGF) gene
      family ligand and receptors on human upper and lower airway epithelial cells.
AB  - BACKGROUND: We previously reported that vascular endothelial cell growth factor
      (VEGF) is abundantly expressed by primary human nasal epithelial cells (PNECs)
      and functions to promote cell hyperplasia in polyposis. Therefore, we aimed to
      examine the full expression profile of other members of the VEGF gene family of
      ligands and receptors, which may play a role in cell growth and the development
      of chronic rhinosinusitis with nasal polyposis (CRSwNP). METHODS: Messenger RNA
      (mRNA) and protein expression of VEGF genes, receptors, and co-receptors was
      examined from cultured PNECs (n = 4) and compared to that from primary human
      bronchial epithelial cells (PBECs; n = 4) and the BEAS2B cell line (n = 4) by
      real-time polymerase chain reaction (PCR) and flow cytometry. RESULTS: We report
      abundant expression of VEGFA, VEGFB, and VEGFC, detected by mRNA and flow
      cytometric analysis on PNECs. We herein report the novel finding that there is
      significant expression of VEGFR1, VEGFR2, VEGFR3, and both neuropilin co
      receptors, NP1 and NP2, at baseline conditions on PNECs. Lower airway PBECs and
      BEAS2B cells displayed similar patterns of expression. CONCLUSION: PNECs express
      high constitutive levels of the VEGF gene family homolog of ligands and
      receptors. Expression of multiple VEGF ligand-receptor combinations may function
      as redundant pathways to promote upper and lower airway epithelial cell growth
      during inflammation.

PMID- 24574254
TI  - Remote stereocontrol transmitted through helicity.

PMID- 24574256
TI  - Time estimation among low-functioning individuals with autism spectrum disorders:
      evidence of poor sensitivity to variability of short durations.
AB  - Time estimation of short durations (under 1 sec) was examined in low-functioning
      individuals with autism spectrum disorder (ASD) and typically developing (TD)
      children matched on mental age. Temporal bisection and generalization tasks were
      used to examine basic perceptual timing mechanisms. For both tasks, the
      participants with ASD demonstrated less sensitivity to variability in short
      durations than the TD children, adding to a growing body of literature suggesting
      deficits in timing exist for longer durations. The results highlight the need to
      examine multiple levels of processing of time-related information from basic
      perceptual mechanisms to higher level cognitive mechanisms.

PMID- 24574255
TI  - Temperature-sensitive magnetic drug carriers for concurrent gemcitabine
      chemohyperthermia.
AB  - To improve the efficacy of gemcitabine (GEM) for the treatment of advanced
      pancreatic cancer via local hyperthermia potentiated via a multi-functional
      nanoplatform permitting both in vivo heating and drug delivery is the goal of
      this study. Here, a chemohyperthermia approach to synergistically achieve high
      intra-tumoral drug concentrations, while permitting concurrent hyperthermia for
      more effective tumor cell kill and growth inhibition, is proposed. Drug delivery
      and hyperthermia are achieved using a hydroxypropyl cellulose (HPC)-grafted
      porous magnetic drug carrier that is MRI visible to permit in vivo visualization
      of the biodistribution. These synthesized magnetic drug carriers produce strong
      T2 -weighted image contrast and permit efficient heating using low-magnetic-field
      intensities. The thermomechanical response of HPC permits triggered GEM release
      confirmed during in vitro drug release studies. During in vitro studies,
      pancreatic cancer cell growth is significantly inhibited (~82% reduction) with
      chemohyperthermia compared to chemotherapy or hyperthermia alone. Using PANC-1
      xenografts in nude mice, the delivery of injected GEM-loaded magnetic carriers
      (GEM-magnetic carriers) is visualized with both MRI and fluorescent imaging
      techniques. Chemohyperthermia with intra-tumoral injections of GEM-magnetic
      carriers (followed by heating) results in significant increases in apoptotic cell
      death compared to tumors treated with GEM-magnetic carriers injections alone.
      Chemohyperthermia with GEM-magnetic carriers offers the potential to
      significantly improve the therapeutic efficacy of GEM for the treatment of
      pancreatic cancer. In vivo delivery confirmation with non-invasive imaging
      techniques could permit patient-specific adjustments therapeutic regimens for
      improve longitudinal outcomes.

PMID- 24574257
TI  - Developing an irreversible inhibitor of human DDAH-1, an enzyme upregulated in
      melanoma.
AB  - Inhibitors of the human enzyme dimethylarginine dimethylaminohydrolase-1 (DDAH-1)
      can raise endogenous levels of asymmetric dimethylarginine (ADMA) and lead to a
      subsequent inhibition of nitric oxide synthesis. In this study, N(5) -(1-imino-2
      chloroethyl)-L-ornithine (Cl-NIO) is shown to be a potent time- and concentration
      dependent inhibitor of purified human DDAH-1 (KI =1.3+/-0.6 MUM; kinact =0.34+/
      0.07 min(-1) ), with >500-fold selectivity against two arginine-handling enzymes
      in the same pathway. An activity probe is used to measure the "in cell" IC50
      value (6.6+/-0.2 MUM) for Cl-NIO inhibition of DDAH-1 artificially expressed
      within cultured HEK293T cells. A screen of diverse melanoma cell lines reveals
      that a striking 50/64 (78 %) of melanoma lines tested showed increased levels of
      DDAH-1 relative to normal melanocyte control lines. Treatment of the melanoma
      A375 cell line with Cl-NIO shows a subsequent decrease in cellular nitric oxide
      production. Cl-NIO is a promising tool for the study of methylarginine-mediated
      nitric oxide control and a potential therapeutic lead compound for other
      indications with elevated nitric oxide production, such as septic shock and
      idiopathic pulmonary fibrosis.

PMID- 24574258
TI  - Probiotics for preventing gestational diabetes.
AB  - BACKGROUND: Gestational diabetes mellitus (GDM) is associated with a range of
      adverse pregnancy outcomes for mother and infant. The prevention of GDM using
      lifestyle interventions has proven difficult. The gut microbiome (the composite
      of bacteria present in the intestines) influences host inflammatory pathways,
      glucose and lipid metabolism and, in other settings, alteration of the gut
      microbiome has been shown to impact on these host responses. Probiotics are one
      way of altering the gut microbiome but little is known about their use in
      influencing the metabolic environment of pregnancy. OBJECTIVES: To assess the
      effects of probiotic supplementation when compared with other methods for the
      prevention of GDM. SEARCH METHODS: We searched the Cochrane Pregnancy and
      childbirth Group's Trials Register (31 August 2013) and reference lists of the
      articles of retrieved studies. SELECTION CRITERIA: Randomised and cluster
      randomised trials comparing the use of probiotic supplementation with other
      methods for the prevention of the development of GDM. Cluster-randomised trials
      were eligible for inclusion but none were identified. Quasi-randomised and cross
      over design studies are not eligible for inclusion in this review. Studies
      presented only as abstracts with no subsequent full report of study results would
      also have been excluded. DATA COLLECTION AND ANALYSIS: Two review authors
      independently assessed study eligibility, extracted data and assessed risk of
      bias of included study. Data were checked for accuracy. MAIN RESULTS: Eleven
      reports (relating to five possible trials) were found. We included one study (six
      trial reports) involving 256 women. Four other studies are ongoing.The included
      trial consisted of three treatment arms: probiotic with dietary intervention,
      placebo and dietary intervention, and dietary intervention alone; it was at a low
      risk of bias. The study reported primary outcomes of a reduction in the rate of
      gestational diabetes mellitus (risk ratio (RR) 0.38, 95% confidence interval (CI)
      0.20 to 0.70), with no statistical difference in the rates of
      miscarriage/intrauterine fetal death (IUFD)/stillbirth/neonatal death (RR 2.00,
      95% CI 0.35 to 11.35). Secondary outcomes reported were a reduction in infant
      birthweight (mean difference (MD) -127.71 g, 95% CI -251.37 to -4.06) in the
      probiotic group and no clear evidence of increased risk of preterm delivery (RR
      3.27, 95% CI 0.44 to 24.43), or caesarean section rate (RR 1.23, 95% CI 0.65 to
      2.32). The primary infant outcomes of rates of macrosomia and large-for
      gestational age infants were not reported. The following secondary outcomes were
      not reported: maternal gestational weight gain, pre-eclampsia, and the long-term
      diagnosis of diabetes mellitus; infant body composition, shoulder dystocia,
      admission to neonatal intensive care, jaundice, hypoglycaemia and long-term rates
      of obesity and diabetes mellitus. AUTHORS' CONCLUSIONS: One trial has shown a
      reduction in the rate of GDM when women are randomised to probiotics early in
      pregnancy but more uncertain evidence of any effect on
      miscarriage/IUFD/stillbirth/neonatal death. There are no data on macrosomia. At
      this time, there are insufficient studies to perform a quantitative meta
      analysis. Further results are awaited from four ongoing studies.

PMID- 24574259
TI  - Assessment of the effect of triton X-114 on the physicochemical properties of an
      antibody fragment.
AB  - The effect of Triton X-114 on the physicochemical properties of a single-chain
      antibody fragment (scFv) has been studied. According to the far UV circular
      dichroism spectroscopy, the secondary structure of the recombinant antibody was
      not significantly affected by the presence of Triton. From the antibody tertiary
      structure analysis, it was found that the surfactant could be located around the
      tryptophan molecules accessible to the solvent, diminishing the polarity of its
      environment but maintaining most of the protein structure integrity. However, in
      certain conditions of high temperature and high concentration of denaturant
      molecules, the presence of TX could compromise the antibody fragment stability.
      These results represent a previous step in designing scFv purification protocols
      and should be considered prior to developing scFv liquid-liquid extraction
      procedures.

PMID- 24574260
TI  - Sex-specific cardiovascular structure and function in heart failure with
      preserved ejection fraction.
AB  - AIMS: Women are more likely to develop heart failure with preserved ejection
      fraction (HFpEF) than men. We studied the relationship between sex and
      cardiovascular structure and function in patients with HFpEF. METHODS AND
      RESULTS: The study included 279 participants from the PARAMOUNT study (57% women)
      with analysable baseline echocardiograms (mean age 71 years, 94% hypertensive,
      38% diabetic). We assessed sex-based differences in baseline clinical
      characteristics and measures of cardiovascular structure/function. Coronary
      artery disease was less common in women than in men. Women were more obese and
      symptomatic, and less likely to have albuminuria. Women had higher indexed left
      ventricular (LV) wall thicknesses, worse diastolic function (lower E', P = 0.002;
      higher E/E', P < 0.001), while LV mass and LV volumes indexed for height(2.7)
      were similar. Nonetheless, female sex was associated with a trend towards higher
      prevalence of abnormal LV geometry (defined as concentric hypertrophy, or
      eccentric hypertrophy, or concentric remodelling) at baseline (unadjusted P =
      0.028, adjusted P = 0.056) and 12 weeks' follow up (unadjusted P = 0.001,
      adjusted P = 0.006), but not at 36 weeks' follow up (unadjusted P = 0.81,
      adjusted P = 0.99). Despite higher LV ejection fraction in women, global LV
      strain was similar between the sexes, while Tissue Doppler Imaging S' mitral
      velocity was lower in women. Both LV diastolic and systolic stiffness were higher
      in women than men (P < 0.001), even adjusting for LV concentricity and clinical
      covariates. We observed no sex differences in systolic arterial-LV coupling, as
      women also had higher absolute arterial elastance compared with men, although
      this difference was not significant after adjusting for height(2.7) . CONCLUSION:
      More pronounced diastolic dysfunction may contribute to the greater
      predisposition for HFpEF in women compared with men.

PMID- 24574261
TI  - Disulfide cross-linked polyurethane micelles as a reduction-triggered drug
      delivery system for cancer therapy.
AB  - Nanoscale carriers that stably load drugs in blood circulation and release the
      payloads in desirable sites in response to a specific trigger are of great
      interest for smart drug delivery systems. For this purpose, a novel type of
      disulfide core cross-linked micelles, which are facilely fabricated by cross
      linking of poly(ethylene glycol)/polyurethane block copolymers containing cyclic
      disulfide moieties via a thiol-disulfide exchange reaction, are developed. A
      broad-spectrum anti-cancer drug, doxorubicin (DOX), is loaded into the micelles
      as a model drug. The drug release from the core cross-linked polyurethane
      micelles (CCL-PUMs) loaded with DOX is suppressed in normal phosphate buffer
      saline (PBS), whereas it is markedly accelerated with addition of an
      intracellular reducing agent, glutathione (GSH). Notably, although DOX-loaded CCL
      PUMs display lower cytotoxicity in vitro compared to either free DOX or DOX
      loaded uncross-linked polyurethane micelles, the drug-loaded CCL-PUMs show the
      highest anti-tumor efficacy with reduced toxicity in vivo. Since enhanced anti
      tumor efficacy and reduced toxic side effects are key aspects of efficient cancer
      therapy, the novel reduction-responsive CCL-PUMs may hold great potential as a
      bio-triggered drug delivery system for cancer therapy.

PMID- 24574262
TI  - The return of the jedi: comparison of the outcomes of endolaser
      dacryocystorhinostomy and endonasal dacryocystorhinostomy.
AB  - BACKGROUND: External dacryocystorhinostomy (DCR) is considered to be the gold
      standard treatment of primary acquired nasolacrimal duct obstruction. A better
      understanding of the endoscopic anatomy of the lacrimal sac has increased the
      success rate of endonasal DCR. Laser DCR has become popular in recent years and
      has a success rate comparable with those of other endonasal techniques. The aim
      of this study was to compare the surgical results of endonasal DCR (EDCR) and
      endonasal laser DCR (ELDCR). METHODS: Fifty-four patients treated with ELDCR and
      42 patients treated with EDCR for nasolacrimal duct obstruction from 2009 to 2012
      with at least 1.5 years of follow-up were retrospectively enrolled in this
      comparative study. Lack of patient complaints and irrigation testing were used as
      subjective and objective assessment tools, respectively. RESULTS: Both groups
      were similar in terms of age and sex. ELDCR had a success rate of 85.2%, and EDCR
      had a success rate of 92.9%. The difference between the 2 procedures was not
      statistically significant. ELDCR had a significantly shorter operative time than
      did EDCR (16.9 vs 24.4 minutes, respectively; p < 0.001). CONCLUSION: Endonasal
      procedures have the advantage of no scar formation and do not disturb the pumping
      mechanism of the lacrimal sac. Their success rates are comparable with those of
      external DCR. Surgery is quicker, and with use of a laser, even less time is
      spent in the operating room. In selected cases, ELDCR can be a good alternative
      method with a high success rate.

PMID- 24574263
TI  - Activation of matrix metalloproteinases 2, 9, and 13 by activated protein C in
      human osteoarthritic cartilage chondrocytes.
AB  - OBJECTIVE: Levels of activated protein C (APC) are elevated in the synovial fluid
      of patients with osteoarthritis (OA), and increased APC levels are correlated
      with the levels of active matrix metalloproteinase 2 (MMP-2). This study sought
      to investigate whether APC is a relevant protein for activation of MMPs in the
      degradation of human OA cartilage, and to elucidate its mechanisms of action.
      METHODS: Human articular cartilage was cultured with or without interleukin
      1alpha (IL-1alpha), in the presence or absence of APC or protein C, and an MMP or
      serine proteinase inhibitor. Aggrecan and collagen release and chondrocyte gene
      expression levels were quantified. Aggrecanase and MMP cleavage of aggrecan was
      examined with neoepitope-specific antibodies, and MMP activity was measured using
      gelatin zymography and fluorogenic peptide assay. RESULTS: In human OA cartilage,
      APC induced aggrecan and collagen release, whereas in non-OA cartilage,
      costimulation with IL-1alpha was required. Inhibition of MMP activity reduced APC
      induced cartilage proteolysis, and MMP-induced aggrecanolysis was confirmed by
      Western blotting. In cultures with APC alone, the activity of MMPs 2, 9, and 13
      was significantly increased in OA cartilage, although APC could not directly
      activate MMPs 2 or 9. Expression of MMP1, MMP2, MMP9, MMP13, TIMP1, and TIMP3 was
      not altered by APC in OA cartilage. Human OA chondrocytes expressed messenger RNA
      for protein C, endothelial protein C receptor, thrombomodulin, and protease
      activated receptor 1, but these were unaltered or down-regulated by APC. The
      induction of MMP activation and cartilage degradation by APC was dependent on its
      serine protease activity. CONCLUSION: APC is a physiologically relevant activator
      of MMPs and cartilage breakdown in human OA. The effects of APC are dependent on
      its proteolytic activity and as-yet-undefined cell and/or cartilage matrix
      factors, and inhibition of this pathway may provide a novel therapeutic target to
      halt the progression of cartilage damage in OA.

PMID- 24574264
TI  - Differential effects of cyclic stretch on bFGF- and VEGF-induced sprouting
      angiogenesis.
AB  - How mechanical factors affect angiogenesis and how they and chemical angiogenic
      factors work in concert remain not yet well-understood. This study investigated
      the interactive effects of cyclic uniaxial stretch and two potent proangiogenic
      molecules [basic fibroblast growth factor (bFGF) and vascular endothelial growth
      factor (VEGF)] on angiogenesis using a stretchable three-dimensional (3-D) cell
      culture model. Endothelial cells seeded atop a 3-D collagen gel underwent
      sprouting angiogenesis while being subjected to either 10 or 20% cyclic uniaxial
      stretch at a frequency of either 1/12 or 1 Hz, in conjunction with an elevated
      concentration of bFGF or VEGF. Without the presence of additional growth factors,
      10 and 20% stretch at 1 Hz induced angiogenesis and the perpendicular alignment
      of new sprouts, and both inductive effects were abolished by cytochalasin D (an
      actin polymerization inhibitor). While "10% stretch at 1 Hz," "20% stretch at 1
      Hz," bFGF, and VEGF were strong angiogenesis stimulants individually, only the
      combination of "20% stretch at 1 Hz" and bFGF had an additive effect on inducing
      new sprouts. Interestingly, the combination of "20% stretch at a lower frequency
      (1/12 Hz)" and bFGF decreased sprouting angiogenesis, even though the level of
      perpendicular alignment of new sprouts was the same for both stretch frequencies.
      Taken together, these results demonstrate that both stretch frequency and
      magnitude, along with interactions with various growth factors, are essential in
      mediating formation of endothelial sprouts and vascular patterning. Furthermore,
      work in this area is warranted to elucidate synergistic or competitive signaling
      mechanisms.

PMID- 24574265
TI  - Photoactive electrospun fibers for inducing cell death.
AB  - A photoactive electrospun material producing reactive oxygen species (ROS) upon
      light irradiation is reported. The phototoxicity of the generated ROS is
      spatially restricted to the fiber-tissue interface by conjugation of the
      photosensitizer to a macromolecule. Photo-triggered ROS is produced on demand and
      repeatedly. It induces death of mammalian cells growing on the material surface
      with high spatial resolution. 

PMID- 24574266
TI  - Histopathological and clinical analysis of chronic rhinosinusitis by subtype.
AB  - BACKGROUND: Chronic rhinosinusitis (CRS) encompasses diverse phenotypic
      expression. Clinical and histological differences suggest 4 CRS subtypes:
      eosinophilic CRS with and without nasal polyps (eCRSwNP, eCRSsNP, respectively)
      and non-eosinophilic CRS with and without nasal polyps (neCRSwNP, neCRSsNP,
      respectively). The mucosal basement membrane (BM) and cilia are believed to play
      roles in CRS pathogenesis by impacting mucociliary clearance and immune barriers.
      This study aimed to identify clinical, surgical, and histopathological subtype
      differences to further elucidate disease mechanisms. METHODS: Ethmoid tissue from
      33 adult CRS patients and 7 controls was obtained during endoscopic sinus or
      other sinonasal surgery (controls) and analyzed by light and transmission
      electron microscopy for BM thickness and presence of cilia. CRS patients were
      categorized into the 4 subtypes, and 22-item Sinonasal Outcome Test (SNOT-22)
      score, endoscopy, computed tomography (CT), and surgical data were compared and
      analyzed for association with histopathology measures. RESULTS: CRS subtypes
      could be distinguished by CT score and surgical data, with eCRSwNP patients
      exhibiting greatest disease severity. Whereas eosinophilia was associated with
      absence of cilia, nasal polyposis showed no association with surgical or
      histopathological measures. No significant difference in BM thickness was found
      between controls and CRS subtypes, but distinctions were found regarding cilia,
      which were less common in eosinophilic subgroups compared to controls and
      neCRSsNP patients. CONCLUSION: CRS subtypes exhibit some differentiating
      histopathological and surgical features. The absence of cilia appears to have an
      important role in the eosinophilic subgroups. Further histologic evaluation is
      warranted to evaluate for possible subtype-specific treatment targets or
      prognostic markers.

PMID- 24574267
TI  - On the research needed to better characterise natural radioactivity accumulated
      in the Arctic by long-range atmospheric transport.

PMID- 24574270
TI  - Novel vaccine delivery system induces robust humoral and cellular immune
      responses based on multiple mechanisms.
AB  - Aiming to enhance the immunogenicity of H5N1 split vaccine, the development of a
      novel antigen delivery system based on quaternized chitosan hydrogel
      microparticles (Gel MPs) with multiple mechanisms of immunity enhancement is
      attempted. Gel MPs based on ionic cross-linking are prepared in a simple and mild
      way. Gel MPs are superior as a vaccine delivery system due to their ability to:
      1) enhance cellular uptake and endosomal escape of antigens in dendritic cells
      (DCs); 2) significantly activate DCs; 3) form an antigen depot and recruit
      immunity cells to improve antigen capture. Further in vivo investigation shows
      that Gel MPs, in comparison to aluminum salts (Alum), LPS, and covalent cross
      linking quaternized chitosan MPs (GC MPs), induce higher humoral and cellular
      immune responses with a mixed Th1/Th2 immunity. In conclusion, these results
      demonstrate that Gel MPs are efficient antigen delivery vehicles based on
      multiple mechanisms to enhance both humoral and cellular immune responses against
      H5N1 split antigen.

PMID- 24574269
TI  - Plasminogen is a joint-specific positive or negative determinant of arthritis
      pathogenesis in mice.
AB  - OBJECTIVE: A fundamental metric in the diagnosis of arthropathies is the pattern
      of joint involvement, including differences in proximal versus distal joints and
      patterns of symmetric or asymmetric disease. The basis for joint selectivity
      among arthritides and/or within a defined disease such as rheumatoid arthritis
      remains enigmatic. Coagulation and fibrinolytic activity are observed in both
      experimental animals with inflammatory joint disease and patients with
      inflammatory arthritis. However, the contribution of specific hemostatic factors
      to joint disease is not fully defined. We sought to determine the contribution of
      the fibrinolytic protease, plasminogen, to tumor necrosis factor alpha (TNFalpha)
      driven arthritis in distinct joints in mice. METHODS: The impact of plasminogen
      and/or fibrinogen genetic deficiencies on arthritis progression was evaluated in
      Tg197 mice genetically predisposed to spontaneous, nonabating, and erosive
      polyarthritis due to exuberant human TNFalpha expression. RESULTS: Elimination of
      plasminogen in Tg197 mice significantly exacerbated the incidence and severity of
      arthritis within the paw joints, but simultaneously and dramatically diminished
      the entire spectrum of pathologies within the knee joints of the same animals.
      These opposing outcomes were both mechanistically linked to fibrin(ogen), in that
      superimposing fibrinogen deficiency reversed both the proarthritic phenotype in
      the paws and arthritis resistance in the knees of plasminogen-deficient mice.
      Intriguingly, the change in disease severity in the knees, but not the paws, was
      associated with a plasminogen-dependent reduction in matrix metalloproteinase 9
      activity. CONCLUSION: Plasminogen is a key molecular determinant of inflammatory
      joint disease capable of simultaneously driving or ameliorating arthritis
      pathogenesis in distinct anatomic locations in the same subject.

PMID- 24574271
TI  - Structural pedicled mucochondral-osteal nasoseptal flap: a novel method for
      orbital floor reconstruction after sinonasal and skull base tumor resection.
AB  - Unrepaired orbital floor defects after sinonasal and skull-base tumor resection
      can lead to herniation of orbital contents into the maxillary or ethmoidal
      sinuses, possibly resulting in infection and significant cosmetic and functional
      deficits. Orbital floor defects are usually repaired using prosthetic implants or
      autogenous material. Nasal septal cartilage has been used previously as a free
      graft for reconstruction. However, its reliance on local vascular supply can
      result in ischemia and necrosis in the postoperative period. The vascularized
      pedicled nasoseptal flap, consisting of mucoperichondrium and mucoperiosteum, is
      routinely used as an effective reconstruction method for endoscopic repair of
      cerebrospinal fluid leaks arising from skull base dural defects. However, this
      flap does not provide rigid structural reconstruction when used alone. We report
      a case of an orbital floor defect repaired using a pedicled mucochondral-osteal
      nasoseptal flap. This technique incorporates the structural component of the
      nasal septal cartilage and bone with the vascularized pedicled nasoseptal flap.
      This repair technique may be useful in patients requiring postoperative
      radiotherapy. 

PMID- 24574273
TI  - Flies and the mouth.
AB  - Oral infections caused by flies are rarely encountered in clinical practice, and
      consequently, there is a paucity of information in the medical and dental
      literature about these conditions. In the present article, we present a concise
      review on oral myiasis or fly-blown disease. A variety of fly species can infest
      the oral tissues and produce an exotic clinical picture. Oral myiasis is mainly
      encountered in the tropics and subtropics, but can also be encountered in the
      western part of the world due to the increase of globalization, immigration, and
      global warming. Commonly-reported symptoms of oral myiasis include pain,
      swelling, itchy sensation, and feeling of something moving in the mouth. The
      surgical debridement of infected tissue with the removal of maggots is the
      treatment of choice in most cases of oral myiasis. 

PMID- 24574272
TI  - Hypoxia modulates the phenotype of osteoblasts isolated from knee osteoarthritis
      patients, leading to undermineralized bone nodule formation.
AB  - OBJECTIVE: To investigate the role of hypoxia in the pathology of osteoarthritic
      (OA) bone by exploring its effect on the phenotype of isolated primary
      osteoblasts from patients with knee OA. METHODS: OA bone samples were collected
      at the time of elective joint replacement surgery for knee or hip OA. Normal bone
      samples were collected postmortem from cadaver donors. Primary osteoblasts were
      isolated from knee OA bone chips and cultured under normoxic or hypoxic (2% O2 )
      conditions. Alkaline phosphatase activity was quantified using an enzymatic
      assay, and osteopontin and prostaglandin E2 (PGE2 ) production was assayed by
      enzyme-linked immunosorbent assay. Total RNA was extracted from bone and
      osteoblasts, and gene expression was profiled by quantitative reverse
      transcription-polymerase chain reaction. RESULTS: Human OA bone tissue sections
      stained positively for carbonic anhydrase IX, a biomarker of hypoxia, and
      exhibited differential expression of genes that mediate the vasculature and blood
      coagulation as compared to those found in normal bone. Culture of primary
      osteoblasts isolated from knee OA bone under hypoxic conditions profoundly
      affected the osteoblast phenotype, including the expression of genes that mediate
      bone matrix, bone remodeling, and bone vasculature. Hypoxia also increased the
      expression of cyclooxygenase 2 and the production of PGE2 by OA osteoblasts.
      Osteoblast expression of type II collagen alpha1 chain, angiopoietin-like 4, and
      insulin-like growth factor binding protein 1 was shown to be mediated by hypoxia
      inducible factor 1alpha. Chronic hypoxia reduced osteoblast- mineralized bone
      nodule formation. CONCLUSION: These findings demonstrate that hypoxia can induce
      pathologic changes in osteoblast functionality consistent with an OA phenotype,
      providing evidence that hypoxia is a key driver of OA pathology.

PMID- 24574274
TI  - Efficiency improvement of an antibody production process by increasing the
      inoculum density.
AB  - Increasing economic pressure is the main driving force to enhance the efficiency
      of existing processes. We developed a perfusion strategy for a seed train reactor
      to generate a higher inoculum density for a subsequent fed batch production
      culture. A higher inoculum density can reduce culture duration without
      compromising product titers. Hence, a better capacity utilization can be
      achieved. The perfusion strategy was planned to be implemented in an existing
      large scale antibody production process. Therefore, facility and process
      constraints had to be considered. This article describes the initial development
      steps. Using a proprietary medium and a Chinese hamster ovary cell line
      expressing an IgG antibody, four different cell retention devices were compared
      in regard to retention efficiency and reliability. Two devices were selected for
      further process refinement, a centrifuge and an inclined gravitational settler. A
      concentrated feed medium was developed to meet facility constraints regarding
      maximum accumulated perfundate volume. A 2-day batch phase followed by 5 days of
      perfusion resulted in cell densities of 1.6 * 10(10) cells L(-1) , a 3.5 fold
      increase compared to batch cultivations. Two reactor volumes of concentrated feed
      medium were needed to achieve this goal. Eleven cultivations were carried out in
      bench and 50 L reactors showing acceptable reproducibility and ease of scale up.
      In addition, it was shown that at least three perfusion phases can be combined
      within a repeated perfusion strategy.

PMID- 24574275
TI  - New insights into Alzheimer's disease amyloid inhibition: nanosized metallo
      supramolecular complexes suppress abeta-induced biosynthesis of heme and iron
      uptake in PC12 cells.
AB  - Nanosized metallo-supramolecular compounds, [Ni2 L3 ](4+) and [Fe2 L3 ](4+) , can
      not only strongly inhibit Abeta aggregation but also reduce the peroxidase
      activity of Abeta-heme. Further studies demonstrate that through blocking the
      heme-binding site, these two compounds can suppress Abeta-induced biosynthesis of
      heme and iron uptake in PC12 cells. This work provides new insights into
      molecular mechanisms of Abeta inhibitors on Abeta-mediated neurotoxicity. 

PMID- 24574276
TI  - Histological findings of an autologous dermal fat graft implanted onto the
      pectoralis major muscle of a rat model.
AB  - BACKGROUND: The aim of this study was to investigate the maintenance of volume as
      a spacer by comparing vascular supply and apoptosis in an implanted autologous
      free dermal fat graft (FDFG) and free fat graft (FFG). An autologous FDFG is a
      material used in plastic surgery and oncoplastic breast surgery that is ideal for
      immediate volume replacement after partial mastectomy because of its easy
      availability and minimal invasion of the donor site; however, immunohistochemical
      findings and survival procedures have not yet been reported. METHODS: An
      experimental protocol using a unique animal model was designed for the present
      study. The expression of vascular endothelial growth factor (VEGF) was measured
      in FDFGs and FFGs implanted onto the pectoral major muscle of Wistar rats. Thirty
      Wistar rats were divided into two groups and postoperatively 1, 2, 4, 8, and 16
      weeks (POW1, 2, 4, 8, 16). Six samples from three rats in each group were used as
      control samples (POW0). RESULTS: The thickness of the implanted FDFG was not
      significantly different from the control sample at POW1, 2, 4, 8, and 16 between
      FDFG and FFG group; however, the thickness at POW8 and 16 was significantly
      lesser in the FFG group than in the control samples. The average proportion of
      fatty tissue to whole tissue ranged from 34.2 to 48.6 % in the FDFG group and
      from 57.2 to 76.7 % in the FFG group during the observation period; however,
      there was no significant difference in the proportion of fatty tissue between
      these two groups. There were no significant differences between the average
      number of VEGF-positive cells in the FDFG group and the FFG group at POW1, 2, 4,
      8, and 16. The average number of TUNEL-positive cells in the early period at POW1
      was significantly lower in the FDFG group than in the FFG group. CONCLUSIONS:
      This rat model was useful for investigating the mechanisms of angiogenesis,
      apoptosis, structure maintenance, and fibromatous changes. From the present
      experimental study, we believe that FDFG is one of the most convenient materials
      currently available to repair small defects at the time of BCS even in the
      clinical field.

PMID- 24574277
TI  - Comparison of different definitions of pathologic complete response in operable
      breast cancer: a pooled analysis of three prospective neoadjuvant studies of
      JBCRG.
AB  - BACKGROUND: Neoadjuvant chemotherapy (NAC) has been accepted as one of the
      standard treatments for operable breast cancer. However, the term pathologic
      complete response (pCR) has not been consistently defined. METHODS: This study
      was a pooled analysis of three prospective studies of NAC conducted by JBCRG and
      was performed to compare the prognostic significance of different definitions of
      pCR. pCRs were defined as follows: QpCR, few or no remaining invasive cancer
      cells in the breast; CpCR, ypT0/is; CpCRbn, ypT0/isypN0; SpCR, ypT0; SpCRbn,
      ypT0ypN0; Grade 2b, only a few remaining cancer cells in the breast. RESULTS: A
      total of 353 patients were included. A Cox proportional hazards model revealed
      that hazard ratios (HRs) of each pCR were lower than 1; however, pCR was
      significant for disease-free survival (DFS) and overall survival (OS) only when
      QpCR, CpCR, and CpCRbn were used (DFS; QpCR, 0.27; CpCR, 0.39; CpCRbn, 0.42,
      SpCR, 0.57, SpCRbn, 0.68: OS; QpCR, 0.12; CpCR, 0.17; CpCRbn, 0.16; SpCR, 0.30,
      SpCRbn, 0.45). Grade 2b was also a significant prognostic variable for DFS and OS
      (HR: DFS, 0.19; OS, 0.15). Neither bone nor brain was the first site of
      recurrence in patients who achieved pCR, irrespective of the definition of pCR.
      Triple-negative and Her2-positive tumors tended to recur in soft tissue more
      frequently than the other subtypes, and luminal tumors had the lowest rate of
      recurrence in the brain. CONCLUSION: Prognostic significance of pCR varied
      according to the definition of pCR, and the pattern of recurrence might be
      different according to pathologic response and subtype.

PMID- 24574278
TI  - Comparison of nasal hyperosmolar xylitol and xylometazoline solutions on quality
      of life in patients with inferior turbinate hypertrophy secondary to nonallergic
      rhinitis.
AB  - BACKGROUND: The purpose of this study was to objectively determine and compare
      the efficacy and effectiveness of xylitol solution (Xlear Nasal Sprey(r))
      compared with xylometazoline and physiological saline with respect to quality of
      life (QoL) in patients with nasal congestion. METHODS: A prospective, randomized
      study was performed in 42 patients who had nasal obstruction and hypertrophied
      turbinate mucosa that was refractory to medical treatment. The study population
      was randomized into 3 groups according to the application of xylometazoline,
      physiological saline, and xylitol hyperosmolar solution. The efficacy of
      treatment was evaluated objectively (4-phase rhinomanometry) and subjectively
      (visual analogue scale VAS.) before and after the application of the nasal
      solutions. QoL was evaluated by means of Rhinoconjunctivitis Quality of Life
      Questionnaire (RQLQ). RESULTS: VAS scores and 4-phase rhinomanometry scores were
      better in the group treated with xylometazoline compared to those treated with
      xylitol or saline. The xylitol procedure yielded better results than the saline
      procedure, but differences were not statistically significant in both objective
      and subjective evaluation methods. For overall QoL, there was a significant
      improvement from baseline for the xylometazoline and xylitol groups. However, the
      improvement in the xylometazoline group was significantly greater than that
      obtained in the xylitol group. CONCLUSION: Xlear Nasal Spray(r) is an effective
      modality in the treatment of nasal congestion and has positive effect on the QoL
      of patients. Further studies are needed in order to plan an ongoing treatment of
      Xlear Nasal Sprey(r) at certain intervals for continuous relief of symptoms and a
      better and longstanding QoL.

PMID- 24574279
TI  - Loop-mediated isothermal amplification assay for rapid diagnosis of malaria
      infections in an area of endemicity in Thailand.
AB  - The loop-mediated isothermal amplification (LAMP) method, developed by our group
      for diagnosis of four human malaria parasites, was evaluated on a large scale at
      a remote clinic in Thailand where malaria is endemic. A total of 899 febrile
      patients were analyzed in this study. LAMP was first evaluated in 219 patients,
      and the result was compared to those of two histidine-rich protein (HRP)-2 rapid
      diagnostic tests (RDTs) and microscopy as a gold standard. LAMP DNA extraction
      was conducted by a simple boiling method, and the test results were assessed
      visually. Sensitivity, specificity, positive predictive value (PPV), and negative
      predictive value (NPV) were 95.7%, 100%, 100%, and 98%, respectively, for LAMP
      and 98.6%, 98%, 95.8%, and 99.3%, respectively, for RDTs. Since RDT-positive
      results were based on one out of two RDTs, the sensitivity of RDTs was slightly
      higher than that of LAMP. However, LAMP tended to be more specific than RDTs.
      LAMP next was evaluated in 680 patients, and the result was compared to that of
      microscopy as a gold standard. Sensitivity, specificity, PPV, NPV, and diagnostic
      accuracy of LAMP were 88.9%, 96.9%, 92.2%, 95.5%, and 94.6%, respectively. Nested
      PCR was used to confirm the discrepant results. Malaria LAMP in a remote clinic
      in Thailand achieved an acceptable result, indicating that LAMP malaria diagnosis
      is feasible in a field setting with limited technical resources. Additionally,
      the rapid boiling method for extracting DNA from dried blood spots proved to be
      simple, fast, and suitable for use in the field. 

PMID- 24574280
TI  - Septic arthritis of a native knee joint due to Corynebacterium striatum.
AB  - We report a case of septic arthritis of a native knee joint due to
      Corynebacterium striatum, a rare and unusual cause of septic arthritis of native
      joints. The isolate was identified by a combination of phenotypic, mass
      spectrometric, and nucleic acid-based assays and exhibited high-level resistance
      to most antimicrobials. 

PMID- 24574281
TI  - Coinfection of Fusobacterium nucleatum and Actinomyces israelii in mastoiditis
      diagnosed by next-generation DNA sequencing.
AB  - Some bacterial infections involve potentially complex mixtures of species that
      can now be distinguished using next-generation DNA sequencing. We present a case
      of mastoiditis where Gram stain, culture, and molecular diagnosis were
      nondiagnostic or discrepant. Next-generation sequencing implicated coinfection of
      Fusobacterium nucleatum and Actinomyces israelii, resolving these diagnostic
      discrepancies. 

PMID- 24574282
TI  - Molecular characterizations of PCR-positive Mycoplasma pneumoniae specimens
      collected from Australia and China.
AB  - Mycoplasma pneumoniae is an important cause of community-acquired pneumonia
      (CAP). In this study, M. pneumoniae strains in PCR-positive specimens collected
      from patients in Sydney, Australia (30 samples), and Beijing, China (83 samples),
      were characterized using multilocus variable-number tandem-repeat (VNTR) analysis
      (MLVA), P1-restriction fragment length polymorphism (RFLP) analysis, and
      sequencing of domain V of the 23S rRNA gene to compare genotype distribution and
      macrolide resistance rates between locations. Eighteen distinct MLVA types were
      identified in specimens from Sydney, of which 10 were known (types E, G, J, M, N,
      P, U, V, S, and X) and 8 previously unknown. Strains were equally distributed
      between P1-RFLP type 1 and type 2 variants. Among samples from Beijing, MLVA
      types E, G, J, P, U, X, and Z and four new types were identified. Most specimens
      belonged to P1-RFLP type 1. A nomenclature based on five VNTR loci is proposed to
      designate MLVA patterns. Macrolide resistance-associated mutations were
      identified in only 1 of 30 specimens (3.3%) from Sydney and 71 of 83 (85.5%) from
      Beijing (P<0.05). This study demonstrated that although multiple individual M.
      pneumoniae strains were circulating in Beijing, the genotypes were less diverse
      than those in Sydney. However, the greatest regional difference was in the
      incidence of macrolide resistance, which may reflect differences in antibiotic
      use and/or measures in resistance control.

PMID- 24574283
TI  - Modified CLSI extended-spectrum beta-lactamase (ESBL) confirmatory test for
      phenotypic detection of ESBLs among Enterobacteriaceae producing various beta
      lactamases.
AB  - The worldwide dissemination of Enterobacteriaceae producing AmpC beta-lactamases
      and carbapenemases makes difficult the phenotypic detection of extended-spectrum
      beta-lactamases (ESBLs), as they may be masked by these additional enzymes. A
      modification of the CLSI ESBL confirmatory test was developed and evaluated in a
      comparative study for its ability to successfully detect ESBLs among
      Enterobacteriaceae producing various carbapenemases (Klebsiella pneumoniae
      carbapenemase [KPC], VIM, NDM, and OXA-48) and plasmidic or derepressed AmpCs.
      The modified CLSI ESBL confirmatory test was performed with cefotaxime and
      ceftazidime disks with and without clavulanate, on which both boronic acid (BA)
      and EDTA were dispensed. A total of 162 genotypically confirmed ESBL-positive
      Enterobacteriaceae isolates (83 carbapenemase/ESBL producers, 25 AmpC/ESBL
      producers, and 54 ESBL-only producers) were examined. For comparison, 139
      genotypically confirmed ESBL-negative Enterobacteriaceae isolates (94 of them
      possessed carbapenemases and 20 possessed AmpCs) were also tested. The standard
      CLSI ESBL confirmatory test was positive for 106 of the 162 ESBL producers
      (sensitivity, 65.4%) and showed false-positive results for 4 of the 139 non-ESBL
      producers (specificity, 97.1%). The modified CLSI ESBL confirmatory test detected
      158 of 162 ESBL producers (sensitivity, 97.5%) and showed no false-positive
      results for non-ESBL producers (specificity, 100%). The findings of the study
      demonstrate that the modified CLSI ESBL confirmatory test using antibiotic disks
      containing both BA and EDTA accurately detects ESBLs in Enterobacteriaceae
      regardless of the coexistence of additional beta-lactam resistance mechanisms. 

PMID- 24574284
TI  - Interlaboratory reproducibility and proficiency testing within the human
      papillomavirus cervical cancer screening program in Catalonia, Spain.
AB  - In Catalonia, a screening protocol for cervical cancer, including human
      papillomavirus (HPV) DNA testing using the Digene Hybrid Capture 2 (HC2) assay,
      was implemented in 2006. In order to monitor interlaboratory reproducibility, a
      proficiency testing (PT) survey of the HPV samples was launched in 2008. The aim
      of this study was to explore the repeatability of the HC2 assay's performance.
      Participating laboratories provided 20 samples annually, 5 randomly chosen
      samples from each of the following relative light unit (RLU) intervals: <0.5, 0.5
      to 0.99, 1 to 9.99, and >=10. Kappa statistics were used to determine the
      agreement levels between the original and the PT readings. The nature and origin
      of the discrepant results were calculated by bootstrapping. A total of 946
      specimens were retested. The kappa values were 0.91 for positive/negative
      categorical classification and 0.79 for the four RLU intervals studied. Sample
      retesting yielded systematically lower RLU values than the original test
      (P<0.005), independently of the time elapsed between the two determinations
      (median, 53 days), possibly due to freeze-thaw cycles. The probability for a
      sample to show clinically discrepant results upon retesting was a function of the
      RLU value; samples with RLU values in the 0.5 to 5 interval showed 10.80%
      probability to yield discrepant results (95% confidence interval [CI], 7.86 to
      14.33) compared to 0.85% probability for samples outside this interval (95% CI,
      0.17 to 1.69). Globally, the HC2 assay shows high interlaboratory concordance. We
      have identified differential confidence thresholds and suggested the guidelines
      for interlaboratory PT in the future, as analytical quality assessment of HPV DNA
      detection remains a central component of the screening program for cervical
      cancer prevention.

PMID- 24574285
TI  - New automated chemiluminescence immunoassay for simultaneous but separate
      detection of human immunodeficiency virus antigens and antibodies.
AB  - The recently launched Liaison XL Murex HIV Ab/Ag assay (DiaSorin S.p.A) uses
      chemiluminescence immunoassay technology for the combined qualitative
      determination of p24 antigen of HIV-1 and specific antibodies to both HIV-1 and
      HIV-2. We studied 571 serum samples from those submitted to our laboratory for
      HIV screening. The samples were divided into 3 subsets: subset A, 365 samples
      collected prospectively during 1 week; subset B, 158 samples from confirmed HIV
      positive patients; and subset C, 48 samples with a positive screening result but
      a negative or indeterminate confirmatory test result. Our standard
      screening/confirmatory algorithm was used as a reference. In subset A
      (prospective), 5 samples were positive and 360 negative by the standard
      procedure. Liaison XL Murex HIV Ab/Ag correctly identified all 5 positive samples
      (100%) and 357 negative samples (99.2%). In subset B (confirmed positive), all
      158 positive samples were in total agreement in both procedures. In subset C
      (screen positive only), Liaison XL Murex HIV Ab/Ag yielded accurate results in 42
      out of 48 samples (87.5%). Global sensitivity and specificity for Liaison XL
      Murex HIV Ab/Ag (all subsets included) were 98.3% and 98.5%, respectively.
      Considering only nonselected prospective samples and confirmed positive samples
      (subsets A and B), the corresponding sensitivity and specificity values were 100%
      and 99.2%, respectively. The new fully automated HIV screening test showed high
      sensitivity and specificity compared to our standard algorithm. Its added
      advantage of being able to detect HIV-1 and HIV-2 antibodies and p24 antigen
      separately could prove useful in the diagnosis of early infections. 

PMID- 24574286
TI  - Demonstration of plasmid-mediated drug resistance in Mycobacterium abscessus.
AB  - Plasmid-mediated kanamycin resistance was detected in a strain of Mycobacterium
      abscessus subsp. bolletii responsible for a nationwide epidemic of surgical
      infections in Brazil. The plasmid did not influence susceptibility to tobramycin,
      streptomycin, trimethoprim-sulfamethoxazole, clarithromycin, or ciprofloxacin.
      Plasmid-mediated drug resistance has not been described so far in mycobacteria. 

PMID- 24574287
TI  - Genetic diversity and evolution of Salmonella enterica serovar Enteritidis
      strains with different phage types.
AB  - Phage typing has been used for the epidemiological surveillance of Salmonella
      enterica serovar Enteritidis for over 2 decades. However, knowledge of the
      genetic and evolutionary relationships between phage types is very limited,
      making differences difficult to interpret. Here, single nucleotide polymorphisms
      (SNPs) identified from whole-genome comparisons were used to determine the
      relationships between some S. Enteritidis phage types (PTs) commonly associated
      with food-borne outbreaks in the United States. Emphasis was placed on the
      predominant phage types PT8, PT13a, and PT13 in North America. With >89,400 bp
      surveyed across 98 S. Enteritidis isolates representing 14 distinct phage types,
      55 informative SNPs were discovered within 23 chromosomally anchored loci. To
      maximize the discriminatory and evolutionary partitioning of these highly
      homogeneous strains, sequences comprising informative SNPs were concatenated into
      a single combined data matrix and subjected to phylogenetic analysis. The
      resultant phylogeny allocated most S. Enteritidis isolates into two distinct
      clades (clades I and II) and four subclades. Synapomorphic (shared and derived)
      sets of SNPs capable of distinguishing individual clades/subclades were
      identified. However, individual phage types appeared to be evolutionarily
      disjunct when mapped to this phylogeny, suggesting that phage typing may not be
      valid for making phylogenetic inferences. Furthermore, the set of SNPs identified
      here represents useful genetic markers for strain differentiation of more clonal
      S. Enteritidis strains and provides core genotypic markers for future development
      of a SNP typing scheme with S. Enteritidis. 

PMID- 24574288
TI  - Development of a two-step multiplex PCR assay for typing of capsular
      polysaccharide synthesis gene clusters of Streptococcus suis.
AB  - We developed a practical and easy two-step multiplex PCR assay to aid in
      serotyping of Streptococcus suis. The assay accurately typed almost all of the
      serotype reference strains and field isolates of various serotypes and also
      identified the genotypes of capsular polysaccharide synthesis gene clusters of
      some serologically nontypeable strains. 

PMID- 24574289
TI  - The role of the clinical laboratory in the future of health care: lean
      microbiology.
AB  - This commentary will introduce lean concepts into the clinical microbiology
      laboratory. The practice of lean in the clinical microbiology laboratory can
      remove waste, increase efficiency, and reduce costs. Lean, Six Sigma, and other
      such management initiatives are useful tools and can provide dividends but must
      be accompanied by organizational leadership commitment to sustaining the lean
      culture in the laboratory setting and providing resources and time to work
      through the process. 

PMID- 24574290
TI  - Real-time whole-genome sequencing for routine typing, surveillance, and outbreak
      detection of verotoxigenic Escherichia coli.
AB  - Fast and accurate identification and typing of pathogens are essential for
      effective surveillance and outbreak detection. The current routine procedure is
      based on a variety of techniques, making the procedure laborious, time-consuming,
      and expensive. With whole-genome sequencing (WGS) becoming cheaper, it has huge
      potential in both diagnostics and routine surveillance. The aim of this study was
      to perform a real-time evaluation of WGS for routine typing and surveillance of
      verocytotoxin-producing Escherichia coli (VTEC). In Denmark, the Statens Serum
      Institut (SSI) routinely receives all suspected VTEC isolates. During a 7-week
      period in the fall of 2012, all incoming isolates were concurrently subjected to
      WGS using IonTorrent PGM. Real-time bioinformatics analysis was performed using
      web-tools (www.genomicepidemiology.org) for species determination, multilocus
      sequence type (MLST) typing, and determination of phylogenetic relationship, and
      a specific VirulenceFinder for detection of E. coli virulence genes was developed
      as part of this study. In total, 46 suspected VTEC isolates were characterized in
      parallel during the study. VirulenceFinder proved successful in detecting
      virulence genes included in routine typing, explicitly verocytotoxin 1 (vtx1),
      verocytotoxin 2 (vtx2), and intimin (eae), and also detected additional virulence
      genes. VirulenceFinder is also a robust method for assigning verocytotoxin (vtx)
      subtypes. A real-time clustering of isolates in agreement with the epidemiology
      was established from WGS, enabling discrimination between sporadic and outbreak
      isolates. Overall, WGS typing produced results faster and at a lower cost than
      the current routine. Therefore, WGS typing is a superior alternative to
      conventional typing strategies. This approach may also be applied to typing and
      surveillance of other pathogens. 

PMID- 24574292
TI  - Benchmarking of methods for genomic taxonomy.
AB  - One of the first issues that emerges when a prokaryotic organism of interest is
      encountered is the question of what it is--that is, which species it is. The 16S
      rRNA gene formed the basis of the first method for sequence-based taxonomy and
      has had a tremendous impact on the field of microbiology. Nevertheless, the
      method has been found to have a number of shortcomings. In the current study, we
      trained and benchmarked five methods for whole-genome sequence-based prokaryotic
      species identification on a common data set of complete genomes: (i)
      SpeciesFinder, which is based on the complete 16S rRNA gene; (ii) Reads2Type that
      searches for species-specific 50-mers in either the 16S rRNA gene or the gyrB
      gene (for the Enterobacteraceae family); (iii) the ribosomal multilocus sequence
      typing (rMLST) method that samples up to 53 ribosomal genes; (iv) TaxonomyFinder,
      which is based on species-specific functional protein domain profiles; and
      finally (v) KmerFinder, which examines the number of cooccurring k-mers
      (substrings of k nucleotides in DNA sequence data). The performances of the
      methods were subsequently evaluated on three data sets of short sequence reads or
      draft genomes from public databases. In total, the evaluation sets constituted
      sequence data from more than 11,000 isolates covering 159 genera and 243 species.
      Our results indicate that methods that sample only chromosomal, core genes have
      difficulties in distinguishing closely related species which only recently
      diverged. The KmerFinder method had the overall highest accuracy and correctly
      identified from 93% to 97% of the isolates in the evaluations sets.

PMID- 24574291
TI  - Direct detection of macrolide resistance in Mycoplasma genitalium isolates from
      clinical specimens from France by use of real-time PCR and melting curve
      analysis.
AB  - Mycoplasma genitalium is a sexually transmitted organism commonly treated with
      azithromycin. However, macrolide resistance has been reported and is associated
      with point mutations in the 23S rRNA gene. To evaluate the prevalence of
      macrolide resistance in M. genitalium isolates from clinical specimens from
      France, we first used a previously reported high-resolution melting assay.
      Because susceptible and resistant M. genitalium isolates were hardly
      discriminated in M. genitalium-positive clinical specimens, we developed a new
      molecular assay for the rapid detection of macrolide resistance. An assay using
      real-time PCR based on fluorescence resonance energy transfer (FRET) coupled with
      melting curve analysis was designed. The assay was first validated on
      characterized macrolide-resistant M. genitalium isolates and then applied to 202
      urogenital M. genitalium-positive specimens collected from 178 patients from
      France in 2011 and 2012. Resistant genotypes were confirmed by 23S rRNA gene
      sequencing. Among the 202 M. genitalium-positive specimens, 155 were amplified,
      demonstrating a sensitivity of 76.7%. A substitution in the 23S rRNA gene was
      found in 14.2% of the patient samples. Nine and six patients had M. genitalium
      isolates with a substitution at positions 2059 and 2058, respectively. In four
      cases, a mixed population of wild-type and mutated M. genitalium isolates was
      observed. The prevalence of M. genitalium macrolide resistance has been stable in
      France since its detection in 2006. Our FRET PCR assay is able to discriminate
      between wild-type and resistant genotypes directly from clinical specimens. This
      assay will allow clinicians to shorten the time to the initiation of effective
      disease treatment. 

PMID- 24574293
TI  - Rapid detection of beta-lactamase-hydrolyzing extended-spectrum cephalosporins in
      Enterobacteriaceae by use of the new chromogenic betaLacta test.
AB  - The chromogenic betaLacta test developed for the rapid detection of beta
      lactamase-hydrolyzing extended-spectrum cephalosporins in Enterobacteriaceae
      revealed good performance with extended-spectrum beta-lactamase (ESBL) producers
      (97.5% true-positive results). However, false-negative results occurred with
      chromosomal AmpC hyperproducers and plasmid AmpC producers, whereas
      uninterpretable results were mostly due to VIM-1 carbapenemase producers and
      possibly low levels of expressed ESBLs. 

PMID- 24574294
TI  - Clinical characteristics of bacteremia caused by Helicobacter cinaedi and time
      required for blood cultures to become positive.
AB  - The aim of this study was to clarify the clinical characteristics of patients
      with Helicobacter cinaedi bacteremia and the time required for blood cultures to
      become positive. The medical records of all patients with H. cinaedi bacteremia
      at Toranomon Hospital and Toranomon Hospital Kajigaya between March 2009 and
      March 2013 were retrospectively reviewed. Sixty-three patients, 34 men and 29
      women with a median age of 67 years (range, 37 to 88 years), were diagnosed with
      H. cinaedi bacteremia. A total of 51,272 sets of blood cultures were obtained
      during the study period, of which 5,769 sets of blood cultures were positive for
      some organism and 126 sets were H. cinaedi positive. The time required for blood
      cultures to become positive for H. cinaedi was <=5 days in 69 sets (55%) and >5
      days in 57 sets (45%). Most patients had an underlying disease, including chronic
      kidney disease (21 cases), solid tumor (19 cases), hematological malignancy (13
      cases), diabetes mellitus (8 cases), chronic liver disease (6 cases), and
      postorthopedic surgery (3 cases). Only 1 patient had no apparent underlying
      disease. The clinical symptoms included cellulitis in 24 cases, colitis in 7
      cases, and fever only in 27 cases, including 7 cases of febrile neutropenia. The
      30-day mortality rate of H. cinaedi bacteremia was 6.3%. In conclusion, most
      cases of H. cinaedi bacteremia occurred in immunocompromised patients. We might
      have overlooked nearly half of the H. cinaedi bacteremia cases if the duration of
      monitored blood culture samples had been within 5 days. Therefore, when
      clinicians suspect H. cinaedi bacteremia, the observation period for blood
      cultures should be extended. 

PMID- 24574295
TI  - Performance of panfungal--and specific-PCR-based procedures for etiological
      diagnosis of invasive fungal diseases on tissue biopsy specimens with proven
      infection: a 7-year retrospective analysis from a reference laboratory.
AB  - A retrospective analysis of real-time PCR (RT-PCR) results for 151 biopsy samples
      obtained from 132 patients with proven invasive fungal diseases was performed.
      PCR-based techniques proved to be fast and sensitive and enabled definitive
      diagnosis in all cases studied, with detection of a total of 28 fungal species. 

PMID- 24574296
TI  - Rolling circle amplification for direct detection of rpoB gene mutations in
      Mycobacterium tuberculosis isolates from clinical specimens.
AB  - Rapid and accurate detection of multidrug resistance (MDR) in Mycobacterium
      tuberculosis is essential to improve treatment outcomes and reduce global
      transmission but remains a challenge. Rifampin (RIF) resistance is a reliable
      marker of MDR tuberculosis (TB) since by far the majority of RIF-resistant
      strains are also isoniazid (INH) resistant. We have developed a rapid, sensitive,
      and specific method for detecting the most common mutations associated with RIF
      resistance, in the RIF resistance determining region (RRDR) of rpoB, using a
      cocktail of six padlock probes and rolling circle amplification (RCA). We used
      this method to test 46 stored M. tuberculosis clinical isolates with known RIF
      susceptibility profiles (18 RIF resistant, 28 susceptible), a standard
      susceptible strain (H37Rv, ATCC 27294) and 78 M. tuberculosis culture-positive
      clinical (sputum) samples, 59 of which grew RIF-resistant strains. All stored
      clinical isolates were correctly categorized, by the padlock probe/RCA method, as
      RIF susceptible or resistant; the sensitivity and specificity of the method, for
      direct detection of phenotypically RIF-resistant M. tuberculosis in clinical
      specimens, were 96.6 and 89.5%, respectively. This method is rapid, simple, and
      inexpensive and has the potential for high-throughput routine screening of
      clinical specimens for MDR M. tuberculosis, particularly in high prevalence
      settings with limited resources. 

PMID- 24574297
TI  - Identification of polybacterial communities in patients with postoperative,
      posttraumatic, and endogenous endophthalmitis through 16S rRNA gene libraries.
AB  - Endophthalmitis is a potential vision-threatening complication following surgical
      procedures (postoperative endophthalmitis [POE]), trauma (posttraumatic
      endophthalmitis [PTE]), and bacteremic seeding of the eye from a distant
      infection site (endogenous endophthalmitis [EE]). Several studies have revealed
      the polybacterial characteristics of endophthalmitis, which make the
      administration of antibiotics to treat the disease challenging. However, until
      now, the polybacterial communities of POE, PTE, and EE have not been precisely
      studied. Hence, the present study was designed to identify the bacterial
      community of endophthalmitis through 16S rRNA gene libraries. Of the 40
      intraocular samples tested, 30 libraries were constructed with bacterial nested
      PCR-positive samples. The obtained recombinant clones were screened through
      amplified rRNA gene restriction analysis (ARDRA) to identify unique clones. The
      multiple types of ARDRA patterns (P=0.345) and diverse bacterial sequences
      (P=0.277) within the libraries revealed the polybacterial nature of infection in
      POE, PTE, and EE. Moreover, to the best of our knowledge, this is the first
      report on polybacterial infection in EE. Gram-positive bacteria, including
      Bacillus spp. (n=19), Streptococcus spp. (n=18), Staphylococcus spp. (n=6),
      Exiguobacterium spp. (n=3), Gemella spp. (n=2), Enterococcus spp. (n=2), a
      Lysinibacillus sp. (n=1), a Clostridium sp. (n=1), and a Nocardia sp. (n=1), and
      Gram-negative bacteria, including Serratia spp. (n=18), Pseudomonas spp. (n=10),
      Enterobacter spp. (n=8), Acinetobacter spp. (n=3), Pantoea spp. (n=3), a
      Haemophilus sp. (n=1), and a Massilia sp. (n=1), were identified. Interestingly,
      among them, 10 bacterial species were not previously reported to be associated
      with endophthalmitis or other ocular infections. Besides, the presence of 4
      unidentifiable clones suggests the possibility of novel organisms that might
      cause eye infections. Therefore, it is recommended that, in addition to the
      polybacterial nature of POE, PTE, and EE infections, the spectrum of the
      pathogenic bacterial community identified in this work should be considered while
      administering antibiotic therapy in suspected endophthalmitis cases.

PMID- 24574298
TI  - Meta-analysis of sonication fluid samples from prosthetic components for
      diagnosis of infection after total joint arthroplasty.
AB  - This meta-analysis included 12 studies that evaluated sonication fluid cultures
      (SFC) for the diagnosis of prosthetic joint infection (PJI). The pooled
      sensitivity and specificity were 0.80 (95% confidence interval [CI], 0.74 to
      0.84) and 0.95 (CI, 0.90 to 0.98), respectively. Subgroup analyses showed that a
      14-day anaerobic culture may improve sensitivity, the use of centrifugation or
      vortexing may improve specificity, and the use of 400 to 500 ml of Ringer's
      solution for containers may improve sensitivity and specificity. The best SFC
      cutoff was >=5 CFU. In conclusion, SFC has high sensitivity and very high
      specificity for diagnosing PJI. 

PMID- 24574299
TI  - Use of mycobacteriophage quantitative PCR on MGIT broths for a rapid tuberculosis
      antibiogram.
AB  - Phenotypic culture-based drug susceptibility testing (DST) for Mycobacterium
      tuberculosis is a valuable tool to identify four to six active drugs for
      individualized multidrug-resistant (MDR) tuberculosis (TB) regimens. Current
      culture-based methods are slow, however; therefore, we evaluated a rapid
      mycobacteriophage-based quantitative PCR (qPCR) assay for use directly on M.
      tuberculosis-positive MGIT broths. We compared phage qPCRs, using a simple cutoff
      of 3 for the DeltaCq value (where Cq is quantification cycle, and DeltaCq is
      calculated as the Cq of starting phage minus the Cq of TB isolates in drug
      containing medium), on 325 clinical M. tuberculosis MGIT broth cultures versus
      the respective subcultured isolates tested by agar proportion. The median
      accuracy for the 13 drugs/concentrations tested was 98%, with most discrepancies
      being false-resistant results. Evaluation of phage qPCR on greater numbers of
      resistant strains of 393 isolates grown on Lowenstein-Jensen medium showed
      similar findings, with a median accuracy, sensitivity, and specificity of 97%,
      90%, and 99%, respectively. This rapid culture-based DST methodology can be
      performed for any drug on TB-positive MGIT broths, with a specimen-to-antibiogram
      turnaround time of approximately 23.9 days, compared with waiting 58.6 days for
      isolate growth on solid medium followed by agar proportion DST. 

PMID- 24574301
TI  - Histomorphologic and histomorphometric characteristics of zygapophyseal joint
      remodeling in ankylosing spondylitis.
AB  - OBJECTIVE: To unravel the mechanisms that control bony ankylosis in ankylosing
      spondylitis (AS). METHODS: Histomorphologic and histomorphometric analyses were
      performed on zygapophyseal joints obtained from 18 patients with AS, 9 patients
      with osteoarthritis (OA), and 10 cadaver donors without a rheumatic disease
      (controls). The proteoglycan content of the cartilage was determined by Safranin
      O staining and the chondrocyte apoptosis according to caspase 3 expression.
      RESULTS: AS joints were categorized into 3 groups according to the morphology of
      the joint surfaces and joint space: group 1 were joints with an open joint space,
      group 2 were joints with cartilaginous fusion, and group 3 were joints with bony
      fusion of the joint surfaces. Progressive loss of the joint space from group 1
      joints to group 3 joints suggests that this grouping corresponds to sequential
      stages of joint remodeling. Cartilage thickness and subchondral bone plate
      thickness declined from group 1 to group 3 (P < 0.01). Increased chondrocyte
      apoptosis rates were found in groups 1 and 2 (P < 0.05), while in group 3, a
      reduction in the proteoglycan content was found (P < 0.001). Bone marrow
      replacement and invasion of the subchondral bone plate by fibrous tissue was
      found predominantly in AS joints in group 2. CONCLUSION: Cartilage degeneration,
      indicated by cartilage thinning, enhanced chondrocyte apoptosis, and proteoglycan
      loss, and subchondral bone thinning, promoted by invasion of the subchondral bone
      plate by a fibrous tissue originating from the bone marrow, are hallmarks of
      joint remodeling in AS.

PMID- 24574302
TI  - Molecular recognition of nucleotides in water by scorpiand-type receptors based
      on nucleobase discrimination.
AB  - The detection of nucleotides is of crucial importance because they are the basic
      building blocks of nucleic acids. Scorpiand-based polyamine receptors
      functionalized with pyridine or anthracene units are able to form stable
      complexes with nucleotides in water, based on coulombic, pi-pi stacking, and
      hydrogen-bonding interactions. This behavior has been rationalized by means of an
      exploration with NMR spectroscopy and DFT calculations. Binding constants were
      determined by potentiometry. Fluorescence spectroscopy studies have revealed the
      potential of these receptors as sensors to effectively and selectively
      distinguish guanosine-5'-triphosphate (GTP) from adenosine-5'-triphosphate (ATP).

PMID- 24574303
TI  - Electrochemical control of the enzymatic polymerization of PEG hydrogels:
      formation of spatially controlled biological microenvironments.
AB  - Control of pH gradient profile at the electrode-electrolyte interfaces allows the
      control of the enzymatic PEG-hydrogel polymerization. By tuning the solution pH,
      buffer capacity, and the applied current, the extent of the local inhibition and
      confinement of the Factor XIII-mediated polymerization of PEG are controlled.
      This technology opens new perspectives for the production of 3D-structured
      biological microenvironments. 

PMID- 24574304
TI  - The usefulness of FDG PET/CT imaging in suspicion of LVAD infection.

PMID- 24574300
TI  - Clinical implications of evolutionary patterns of homologous, full-length
      hepatitis B virus quasispecies in different hosts after perinatal infection.
AB  - Chronic hepatitis B virus (HBV) infection via perinatal transmission is common in
      the Asia-Pacific region, but related quasispecies (QS) characteristics are not
      yet defined. To investigate the homologous, full-length HBV QS after perinatal
      infection and their clinical implications, five pairs of mother-daughter patients
      with chronic HBV infection (one patient with liver cirrhosis, one with immune
      tolerance, and eight with chronic hepatitis) were included. Full-length HBV were
      amplified by PCR from serum samples before antiviral treatment and cloned; an
      average of 17 clones per sample were sequenced, and the QS complexities,
      diversities, and evolution patterns were analyzed. Full-length HBV sequence
      similarities within mother-daughter pairs were 91.3 to 98.3%. The QS complexities
      of full-length HBV were similar between mothers and daughters (median of 0.9734
      compared to 0.9688, P>0.05), as were the diversities (median of 3.396*10(-3)
      compared to 4.617*10(-3) substitutions/site, P>0.05). However, the distribution
      patterns of QS complexities and diversities within specific genes were different,
      and QS genetic distances of the mothers were higher than those of daughters, both
      more evident in pairs with different antiviral responses and different immune
      phases or stages. The nucleotide substitution rate of full-length HBV was
      14.388*10(-5) substitutions/site/year, whereas the preC/C gene rate was the
      highest. Mutations and indels were more common in clones from the mothers, which
      decreased the affinity of epitopes by 6- to 89-fold. The various genes from
      homologous HBV genomes evolved in different patterns despite numerically
      comparable full-length QS complexities and diversities. The different patterns
      may correlate with the immune stages of chronic HBV infection, which warrants
      further study.

PMID- 24574305
TI  - Oral helminthic infestations.
AB  - Oral infections caused by helminths (worms) are rarely encountered in clinical
      practice, and consequently, there is a paucity of information in the medical and
      dental literature about these conditions. In the present article, we review the
      English literature related to oral helminthic infestations. The main oral
      infections caused by helminths include four roundworm (trichinosis, trichuriasis,
      filariasis, and larva migrans) and three tapeworm infections (cysticercosis,
      sparganosis, and echinococcosis). Cases are mainly encountered in endemic areas
      and mainly present a benign clinical picture. The diagnosis of oral helminthic
      infections is mostly established after histopathological examination, which shows
      parasitic larvae lined by fibrous tissue and inflammatory cells. Surgical
      excision is the preferred treatment of isolated oral lesions caused by helminths;
      however, patients should undergo thorough medical evaluation to exclude the
      possible involvement of other body systems. 

PMID- 24574306
TI  - Effect of the DnaK chaperone on the conformational quality of JCV VP1 virus-like
      particles produced in Escherichia coli.
AB  - Protein nanoparticles such as virus-like particles (VLPs) can be obtained by
      recombinant protein production of viral capsid proteins and spontaneous self
      assembling in cell factories. Contrarily to infective viral particles, VLPs lack
      infective viral genome while retaining important viral properties like cellular
      tropism and intracellular delivery of internalized molecules. These properties
      make VLPs promising and fully biocompatible nanovehicles for drug delivery. VLPs
      of human JC virus (hJCV) VP1 capsid protein produced in Escherichia coli elicit
      variable hemagglutination properties when incubated at different NaCl
      concentrations and pH conditions, being optimal at 200 mM NaCl and at pH range
      between 5.8 and 7.5. In addition, the presence or absence of chaperone DnaK in E.
      coli cells influence the solubility of recombinant VP1 and the conformational
      quality of this protein in the VLPs. The hemagglutination ability of hJCV VP1
      VLPs contained in E. coli cell extracts can be modulated by buffer composition in
      the hemagglutination assay. It has been also determined that the production of
      recombinant hJCV VP1 in E. coli is favored by the absence of chaperone DnaK as
      observed by Western Blot analysis in different E. coli genetic backgrounds,
      indicating a proteolysis targeting role for DnaK. However, solubility is highly
      compromised in a DnaK(-) E. coli strain suggesting an important role of this
      chaperone in reduction of protein aggregates. Finally, hemagglutination
      efficiency of recombinant VP1 is directly related to the presence of DnaK in the
      producing cells.

PMID- 24574308
TI  - Predictive factors to differentiate between allergic and nonallergic rhinitis in
      children.
AB  - BACKGROUND: Although symptoms and signs of allergic rhinitis (AR) and nonallergic
      rhinitis (NAR) are similar, treatment and follow-up are different. We aimed to
      find predictive factors that can be used in primary health care to differentiate
      AR from NAR. METHODS: We made a retrospective analysis of cases aged 6-18 years
      old who were diagnosed as having chronic rhinitis within a 1-year period. Skin
      prick tests were done and severity of rhinitis symptoms was recorded on a visual
      analog scale in all patients. RESULTS: There were 472 cases whose medical records
      were complete and included in the analysis. The median age was 11 (interquartile
      range [IQR], 5) years. AR was diagnosed in 363 patients (76.9%) and was different
      from NAR with respect to: median age (p = 0.042), seasonality of the symptoms (p
      = 0.002), persistent symptoms (p = 0.003), moderate/severe according to visual
      analogue scale (VAS) score (p = 0.017), conjunctivitis (p < 0.001), parental
      history of AR (p = 0.026), rhinorrhea (p < 0.001), sneezing (p = 0.005), mucosal
      pallor (p = 0.004), and response to antihistamines (p = 0.035). All parameters
      with a significance of p < 0.1 between AR and NAR were included in logistic
      regression analysis. Seasonality, sneezing, moderate/severe rhinitis, and
      response to antihistamines were identified as significant independent parameters
      to differentiate AR from NAR. CONCLUSION: Features of rhinitis patients with
      seasonality, sneezing, moderate/severe rhinitis, and response to antihistamines
      may help in differentiation of AR from NAR at the primary care level.

PMID- 24574309
TI  - Does a genetic variant in FOXO3A predict a milder course of rheumatoid arthritis?

PMID- 24574307
TI  - Generalized and specific neurocognitive deficits in psychotic disorders: utility
      for evaluating pharmacological treatment effects and as intermediate phenotypes
      for gene discovery.
AB  - A growing body of research suggests that schizophrenia and bipolar disorder share
      overlapping clinical, neurobiological, and genetic features, raising important
      questions about the boundaries and distinctiveness of these 2 major psychiatric
      disorders. A generalized cognitive impairment has long been understood to be a
      core feature of schizophrenia. More recently, it has become apparent that
      cognitive impairment also occurs in bipolar disorder, particularly in those
      patients with a history of psychotic symptoms. Whether a generalized deficit
      exists across a spectrum of psychotic disorders is less clearly established.
      Additionally, in the context of a broad impairment, it remains a significant
      challenge to identify deficits in specific cognitive processes that may have
      distinct neurochemical or regional brain substrates and linkages to particular
      risk-associated genetic factors. In this article, we review the findings from
      neuropsychological studies across a spectrum that includes schizophrenia,
      schizoaffective and bipolar disorders, and conclude the available evidence
      strongly supports that a generalized deficit is present across psychotic
      disorders that differs in severity more so than form. We then consider the
      implications of generalized and specific deficits in psychosis for 2 areas of
      research--the evaluation of pharmacological treatments targeting cognitive
      deficits, and the investigation of cognitive intermediate phenotypes in family
      genetic studies. Examples from the literature that touch on the relevance of the
      generalized deficit in these contexts are provided, as well as consideration for
      the continued need to identify specific impairments that are separable from the
      generalized deficit in order to advance drug and gene discovery.

PMID- 24574310
TI  - Minor enantiomer recycling: application to enantioselective syntheses of beta
      blockers.
AB  - Continuous recycling of the minor product enantiomer obtained from the
      acetylcyanation of prochiral aldehydes provided access to highly enantiomerically
      enriched products. Cyanohydrin derivatives, which under normal conditions are
      obtained with modest or poor enantiomeric ratios, were formed with high
      enantiomeric purity by using a reinforcing combination of a chiral Lewis acid
      catalyst and a biocatalyst. The primarily obtained products were transformed into
      beta-adrenergic antagonists (S)-propanolol, (R)-dichloroisoproterenol, and (R)
      pronethalol by means of a two-step procedure. 

PMID- 24574311
TI  - Bioactive supramolecular peptide nanofibers for regenerative medicine.
AB  - Recent advances in understanding of cell-matrix interactions and the role of the
      extracellular matrix (ECM) in regulation of cellular behavior have created new
      perspectives for regenerative medicine. Supramolecular peptide nanofiber systems
      have been used as synthetic scaffolds in regenerative medicine applications due
      to their tailorable properties and ability to mimic ECM proteins. Through
      designed bioactive epitopes, peptide nanofiber systems provide biomolecular
      recognition sites that can trigger specific interactions with cell surface
      receptors. The present Review covers structural and biochemical properties of the
      self-assembled peptide nanofibers for tissue regeneration, and highlights studies
      that investigate the ability of ECM mimetic peptides to alter cellular behavior
      including cell adhesion, proliferation, and/or differentiation. 

PMID- 24574312
TI  - Analysis of AM-2201 and metabolites in a drugs and driving case.
AB  - This case report describes the analysis of AM-2201 in plant material and its
      metabolites in human urine obtained from an operator of a motor vehicle in the
      United States. The samples were taken from the driver because of his illegal
      driving activities and, his subsequent erratic behaviour. The AM-2201 was
      extracted from a sample of plant material by sonicating it in methanol, after
      which an aliquot was taken and diluted with aqueous phosphate buffer (pH 6) and
      extracted by solid-phase extraction using a C8/aminopropyl SPE cartridge. The
      cartridges were washed, dried, and eluted with ethyl acetate- methanol solvent
      system. The urine sample was hydrolyzed with beta-glucuronidase at pH 6.8 before
      being diluted with aqueous phosphate buffer (pH 6) and extracted with the same
      type of SPE cartridge. After evaporation of the eluates, the samples were
      dissolved in mobile phase for analysis by liquid chromatography-tandem mass
      spectrometry (LC-MS/MS). Analysis of the plant material determined the
      concentration to be 0.05% (AM2201) by mass of dry material. The concentration of
      AM-2201 (AM2201-N-(4-hydroxypentyl ) metabolite in the urine was found to be 3.1
      ng/ml. The urine also contained 109 ng/ml of delta-9-tetrahydrocannabinol
      carboxylic acid but no other drugs including JWH-018 metabolites.

PMID- 24574314
TI  - Society and community: the role of the Netherlands Society of Cardiology.

PMID- 24574313
TI  - Negative predictive value of SPECT for the occurrence of MACE in a medium-sized
      clinic in the Netherlands.
AB  - BACKGROUND: Single-photon emission computed tomography (SPECT) is an important
      prognostic tool in evaluating coronary artery disease (CAD), with a high negative
      predictive value (NPV) for the occurrence of major adverse cardiac events (MACE).
      The prognostic value of SPECT is disputed in women, patients with atrial
      fibrillation (AF), diabetes, left bundle branch block (LBBB) and renal
      impairment. METHODS: Seven hundred sixty-two patients without prior history of
      CAD who had SPECT without perfusion deficits were followed for 2 years for MACE.
      Predictive variables for the occurrence of MACE were reviewed by Cox proportional
      hazard regression, considering clinical information, resting-ECG data and SPECT
      data. RESULTS: The NPV of SPECT for the occurrence of MACE within 2 years was
      95.8 %. Multivariate Cox regression revealed male gender as the only significant
      predictor for the occurrence of MACE, besides a positive stress ECG at SPECT and
      a low LVEF. AF, LBBB, renal impairment and diabetes had no significant effect on
      the prognosis after normal SPECT. CONCLUSION: SPECT with normal perfusion images
      has great NPV in a medium-sized clinic in the Netherlands, even in patients with
      LBBB, AF, diabetes and renal impairment. MACE-free survival, however, was
      negatively influenced by male gender; we therefore propose more caution in men.

PMID- 24574315
TI  - 80 years of Netherlands Society of Cardiology.

PMID- 24574316
TI  - Impact factor 2013 of the Netherlands Heart Journal surpasses 2.0.
AB  - The impact factor of the Netherlands Heart Journal was stable at about 1.4
      between 2009 and 2012. In 2013 it will break through the 2.0 barrier for the
      first time. 

PMID- 24574317
TI  - Comparison of two laboratory extraction techniques for the detection of Epstein
      Barr virus in the saliva of nasopharyngeal carcinoma patients.
AB  - AIM: The aim of the present study was to compare the effectiveness of DNA
      extraction using an extraction kit against the standard boiling technique for the
      detection of Epstein-Barr virus (EBV) DNA in nasopharyngeal carcinoma (NPC)
      patients. METHODS: Stimulated whole saliva samples from newly-diagnosed NPC
      patients were collected. EBV DNA was extracted by both techniques (n = 23)
      followed by quantitative real-time polymerase chain reaction (PCR) using the
      primer/probe set for BALF5. RESULTS: The results of the quantitative real-time
      PCR were reproducible in both groups. The two techniques were moderately
      correlated (r = 0.67, P < 0.05), and the degree of agreement was good. However,
      the mean EBV DNA level in the boiling group (3.02 +/- 8.67 * 10(6) copies/MUL)
      was significantly higher than the extraction kit group (1.15 +/- 2.66 * 10(6)
      copies/MUL) (P < 0.05). The EBV DNA level was higher in patients at an advanced
      overall stage (P = 0.05). CONCLUSION: The results of the present study showed
      that the performance of the extraction kit was not superior to the simple boiling
      technique for the detection of salivary EBV DNA in NPC patients using real-time
      PCR. The salivary EBV DNA level in patients at an advanced overall stage appeared
      to be higher than in patients at an early stage.

PMID- 24574319
TI  - Studies of preclinical rheumatoid arthritis synovial histology-a comparison of
      animal models: comment on the article by de Hair et al.

PMID- 24574318
TI  - Cholelithiasis and the risk of liver cancer: results from cohort studies of
      134,546 Chinese men and women.
AB  - BACKGROUND: Cholelithiasis and cholecystectomy have been proposed as risk factors
      for liver cancer, but findings have been inconsistent. We assessed this
      association using data from the Shanghai Women's and Men's Health Studies.
      METHODS: History of cholelithiasis and cholecystectomy were reported at baseline
      and follow-up interviews, and liver cancer diagnoses were ascertained from the
      Shanghai Cancer Registry and Vital Statistics Unit. Adjusted hazard ratios (aHRs)
      and 95% CIs were calculated after adjustment for potential confounders. RESULTS:
      A history of cholelithiasis and cholecystectomy was reported by 9.5% and 3.6% of
      participants at baseline, respectively. After a total of 859,882 person-years of
      follow-up for women and 391,093 for men, incident liver cancer was detected in
      160 women and 252 men. A positive association was observed between a history of
      cholelithiasis or cholecystectomy and liver cancer in men (aHR 1.46; 95% CI 1.02
      to 2.07) and women (aHR 1.55; 95% CI 1.06 to 2.26). Similar results were observed
      for cholelithiasis only, but cholecystectomy did not reach statistical
      significance. There was no strong evidence for detection bias of liver cancer due
      to cholelithiasis or cholecystectomy. CONCLUSIONS: Our study suggests that
      cholelithiasis and possibly cholecystectomy may increase the risk of liver
      cancer.

PMID- 24574322
TI  - Co(3)O(4)@CeO(2) core@shell cubes: designed synthesis and optimization of
      catalytic properties.
AB  - Mastery of nanomaterial structure enables the control of its properties to
      enhance its performance for a given application. Herein, we demonstrate a fast
      and facile self-assembly method for the synthesis of a series of Co3 O4 @CeO2
      core@shell cubes, which are characterized by SEM, TEM, XRD, inductively coupled
      plasma mass spectrometry (ICP-MS), and X-ray photoelectron spectroscopy (XPS)
      analyses. The results indicate that the thickness of the CeO2 shell can be tuned
      through simple variation of the feeding molar ratio of Ce/Co. These Co3 O4 @CeO2
      core@shell cubes are used for catalytic CO oxidation and show good catalytic
      properties. Moreover, the relationship between the catalytic performance and the
      CeO2 shell thickness is studied in depth to optimize the catalytic properties. 

PMID- 24574320
TI  - Silibinin inhibits accumulation of myeloid-derived suppressor cells and tumor
      growth of murine breast cancer.
AB  - Myeloid-derived suppressor cells (MDSC)s increase in blood and accumulate in the
      tumor microenvironment of tumor-bearing animals, contributing to immune
      suppression in cancer. Silibinin, a natural flavonoid from the seeds of milk
      thistle, has been developed as an anti-inflammatory agent and supportive care
      agent to reduce the toxicity of cancer chemotherapy. The goals of this study were
      to evaluate the effect of silibinin on MDSCs in tumor-bearing mice and antitumor
      activity of silibinin in a mouse model of breast cancer. 4T1 luciferase
      transfected mammary carcinoma cells were injected into in the mammary fat pad
      female BALB/c mice, and female CB17-Prkdc Scid/J mice. Silibinin treatment
      started on day 4 or day 14 after tumor inoculation continued every other day.
      Tumor growth was monitored by bioluminescent imaging (BLI) measuring total photon
      flux. Flow cytometry measured total leukocytes, CD11b(+) Gr-1(+) MDSC, and T
      cells in the blood and tumors of tumor-bearing mice. The effects of silibinin on
      4T1 cell viability in vitro were measured by BLI. Treatment with silibinin
      increased overall survival in mice harboring tumors derived from the 4T1
      luciferase breast cancer cell line, and reduced tumor volumes and numbers of
      CD11b(+) Gr-1(+) MDSCs in the blood and tumor, and increased the content of T
      cells in the tumor microenvironment. Silibinin failed to inhibit tumor growth in
      immunocompromised severe combined immunodeficiency mice, supporting the
      hypothesis that anticancer effect of silibinin is immune-mediated. The antitumor
      activity of silibinin requires an intact host immune system and is associated
      with decreased accumulation of blood and tumor-associated MDSCs. 

PMID- 24574323
TI  - Characterizing metabolites and potential metabolic pathways for the novel
      psychoactive substance methoxetamine.
AB  - The classic approach of controlled volunteer studies to study drug metabolism is
      difficult or impossible to undertake for novel psychoactive substances (NPS), as
      there is generally very limited information available to allow appropriate dose
      finding and safety. A viable and powerful alternative is the identification and
      characterization of phase I and II metabolites of such drugs by examining the
      concordance of data gathered from analysis of microsomal incubates with that from
      analysis of specimens collected from individuals with analytically confirmed use
      of NPS. Liquid chromatography-high resolution mass spectrometry provides the
      ability to reliably identify such metabolites. We used this technique here to
      study the metabolism of the ketamine analogue methoxetamine. A large number of
      metabolites were identified in the in vitro studies including normethoxetamine, O
      desmethylmethoxetamine, dihydromethoxetamine, dehydromethoxetamine and several
      structural isomers of hydroxymethoxetamine and hydroxynormethoxetamine. pH
      dependent liquid-liquid extraction was used to discriminate phenolic from
      alcoholic metabolites. Phase II glucuronide conjugates included those of O
      desmethylmethoxetamine, O-desmethylnormethoxetamine and O
      desmethylhydroxymethoxetamine. The majority of these phase I and II metabolites
      were confirmed to be present in urine collected from three individuals presenting
      with acute methoxetamine toxicity.

PMID- 24574321
TI  - Click hybridization of immune cells and polyamidoamine dendrimers.
AB  - Immobilizing highly branched polyamidoamine (PAMAM) dendrimers to the cell
      surface represents an innovative method of enhancing cell surface loading
      capacity to deliver therapeutic and imaging agents. In this work, hybridized
      immune cells, that is, macrophage RAW264.7 (RAW), with PAMAM dendrimer G4.0 (DEN)
      on the basis of bioorthogonal chemistry are clicked. Efficient and selective cell
      surface immobilization of dendrimers is confirmed by confocal microscopy.
      Viability and motility of RAW-DEN hybrids remain the same as untreated RAW cells
      according to WST-1 assay and wound closure assay. Furthermore, Western blot
      analysis reveals that there are no significant alterations in the expression
      levels of signaling molecules AKT, p38, and NFkappaB (p65) and their
      corresponding activated (phosphorylated) forms in RAW cells treated with azido
      sugar and dendrimer, indicating that the hybridization process neither induced
      cell stress response nor altered normal signaling pathways. Taken together, this
      work shows the feasibility of applying bioorthogonal chemistry to create cell
      nanoparticle hybrids and demonstrates the noninvasiveness of this cell surface
      engineering approach. 

PMID- 24574325
TI  - Editorial: macrophages and dendritic cells in motion: tracking inflammation and
      fibrosis.

PMID- 24574324
TI  - Success rates of different management techniques for impacted mandibular canines
      and associated complications in children and adolescents.
AB  - AIM: The aim of the present study was to investigate the success rate of various
      treatment modalities and complications associated with the occurrence and
      treatment of impacted mandibular permanent canines. METHODS: Seventy-four
      southern Chinese children and adolescents who received treatment for impacted
      mandibular canines over a 27-year period were included in the analysis. Treatment
      modalities and complications that had been recorded in the clinical and surgical
      notes and that could be diagnosed from the available radiographs were noted.
      RESULTS: The most commonly-performed treatment for the correction of an impacted
      mandibular canine was surgical removal of the impacted tooth (n = 59). In cases
      where surgical exposure of the impacted canine followed by bonding an attachment
      was performed (n = 7), the average time required for the canine to erupt
      postoperatively through the soft tissue was 12.2 months (+/-10.2 months). Lack of
      movement of the tooth after traction was the only complication reported in these
      patients (n = 3). The most frequently-reported postoperative sequela observed for
      all treatment modalities was swelling of the soft tissues around the surgical
      site (n = 6), and this was persistent even after 48 h. CONCLUSIONS: The success
      rate after surgical intervention and orthodontic traction was 57.1%.

PMID- 24574326
TI  - Perfusion seed cultures improve biopharmaceutical fed-batch production capacity
      and product quality.
AB  - Volumetric productivity and product quality are two key performance indicators
      for any biopharmaceutical cell culture process. In this work, we showed proof-of
      concept for improving both through the use of alternating tangential flow
      perfusion seed cultures coupled with high-seed fed-batch production cultures.
      First, we optimized the perfusion N-1 stage, the seed train bioreactor stage
      immediately prior to the production bioreactor stage, to minimize the consumption
      of perfusion media for one CHO cell line and then successfully applied the
      optimized perfusion process to a different CHO cell line. Exponential growth was
      observed throughout the N-1 duration, reaching >40 * 10(6) vc/mL at the end of
      the perfusion N-1 stage. The cultures were subsequently split into high-seed (10
      * 10(6) vc/mL) fed-batch production cultures. This strategy significantly
      shortened the culture duration. The high-seed fed-batch production processes for
      cell lines A and B reached 5 g/L titer in 12 days, while their respective low
      seed processes reached the same titer in 17 days. The shortened production
      culture duration potentially generates a 30% increase in manufacturing capacity
      while yielding comparable product quality. When perfusion N-1 and high-seed fed
      batch production were applied to cell line C, higher levels of the active protein
      were obtained, compared to the low-seed process. This, combined with
      correspondingly lower levels of the inactive species, can enhance the overall
      process yield for the active species. Using three different CHO cell lines, we
      showed that perfusion seed cultures can optimize capacity utilization and improve
      process efficiency by increasing volumetric productivity while maintaining or
      improving product quality.

PMID- 24574327
TI  - New phenethylamines in Europe.
AB  - Sixteen phenethylamines are now included in Schedules I and II of the United
      Nations 1971 Convention on Psychotropic Substances. Most of the ring-substituted
      compounds are in Schedule I, whereas 2C-B, amphetamine, and methamphetamine are
      listed in Schedule II. Substances in Schedule IV (e.g. benzphetamine) are now
      regarded as obsolete pharmaceutical products. They all represent the 'old
      phenethylamines'. By 2013, nearly 100 illicit phenethylamines had been found in
      the European Union (EU). Of these, nine (MBDB, 4-MTA, PMMA, 2C-I, 2C-T-2, 2C-T-7,
      TMA-2, 5-IT and 4-MA) were submitted for risk assessment by the European
      Monitoring Centre for Drugs and Drug Addiction (EMCDDA). All except MBDB were
      recommended for EU-wide control. Of the 'new phenethylamines', 2C-B was the most
      commonly reported, but other 2C compounds were widespread. Many of the ring
      substituted phenethylamines are described in the 1991 book PIHKAL. Many fused
      ring phenethylamines have appeared in the past few years; they include further
      benzofurans (e.g. 5-and 6-APB), indanylalkylamines (e.g. 5-IAP), dibenzofurans
      (e.g. 2C-B-FLY) and 2-aminopropylindoles (e.g.5-IT). The recent and rapid rise of
      phenethylamines with bulky N-substituents (e.g. 25I-NBOMe) has been particularly
      significant. Although not phenethylamines, it is notable that the thiophene
      bioisosteres of amphetamine and methamphetamine as well as certain
      conformationally-restricted variants (e.g. aminoindanes) have been found in
      recent drug seizures. In the United Kingdom Misuse of Drugs Act, most ring
      substituted phenethylamines are either listed by name or are covered by generic
      definitions dating from 1977. In 2013, temporary generic legislation included a
      number of benzofurans, indanylalkylamines and certain 'NBOMe' compounds.

PMID- 24574328
TI  - C,C- and N,C-coupled dimers of 2-aminotetraphenylporphyrins: regiocontrolled
      synthesis, spectroscopic properties, and quantum-chemical calculations.
AB  - beta,beta'-Bisporphyrins are intrinsically chiral porphyrin dimers with
      fascinating properties. The configurational stability at their axes can be
      directed by variation of the central metal atoms. Herein, we present a
      regioselective functionalization of the monomeric 2-amino-tetraphenyl-porphyrin
      as a versatile substrate for dimerization by oxidative coupling. By simple
      variation of the reaction conditions (solvent and oxidant), the oxidation
      selectively gave either the axially chiral C,C-coupled diaminobisporphyrin in
      high yields or, under Ullmann conditions, the twofold N,C-linked achiral dimer,
      also in good yields. A generalized mechanism for the coupling reaction is
      proposed based on DFT calculations. The axially chiral beta,beta'-coupled
      porphyrin dimers were isolated as racemic mixtures, but can be resolved by HPLC
      on a chiral phase. TDDFT and coupled-cluster calculations were used to explain
      the spectroscopic properties of the aminoporphyrins and their dimers and to
      elucidate the absolute configurations of the C,C-coupled bisporphyrins. 

PMID- 24574329
TI  - Association of serum C-reactive protein levels with lupus disease activity in the
      absence of measurable interferon-alpha and a C-reactive protein gene variant.
AB  - OBJECTIVE: The type I interferon (IFN) system is important in the pathogenesis of
      systemic lupus erythematosus (SLE). We previously demonstrated an inhibitory
      effect of IFNalpha on interleukin-6 (IL-6)-induced C-reactive protein (CRP) in
      vitro, hypothetically explaining the poor correlation between disease activity
      and CRP levels in SLE. This study was undertaken to investigate disease activity,
      IL-6 levels, and CRP levels in relation to a CRP gene polymorphism and IFNalpha.
      METHODS: Sera from 155 SLE patients and 100 controls were analyzed for CRP.
      Patients were genotyped for a CRP single-nucleotide polymorphism (rs1205)
      associated with low CRP levels. Serum IFNalpha and IL-6 levels were quantified by
      immunoassays. Clinical disease activity was assessed using the SLE Disease
      Activity Index 2000 (SLEDAI-2K). RESULTS: CRP levels were increased in SLE
      patients compared to controls, but were not associated with SLEDAI-2K or IL-6
      levels. However, exclusion of patients carrying at least one rs1205 minor allele
      revealed an association between disease activity and CRP levels (P = 0.005). We
      found a strong association between disease activity and CRP levels (P < 0.0005)
      when patients with measurable IFNalpha levels as well as the minor allele of
      rs1205 were excluded from the analysis. Similarly, when patients with elevated
      IFNalpha levels and/or the rs1205 polymorphism were excluded, IL-6 levels were
      associated with CRP levels. CONCLUSION: The present study demonstrates that the
      serum IFNalpha level as well as the CRP genotype affect the CRP response in SLE
      patients. Lack of correlation between serum levels of CRP and disease activity
      could therefore be explained by activation of the type I IFN system and
      polymorphisms in the CRP gene.

PMID- 24574331
TI  - Enantioselective disposition of (R/S)-albuterol in skeletal and cardiac muscle.
AB  - Significant enhancement of skeletal muscle function has been observed with
      racemic albuterol (salbutamol). There is now general acceptance that the R
      albuterol enantiomer elicits the pharmacological response, both in the lungs and
      extrapulmonary, while S-albuterol is pharmacologically inert. The objective of
      this study was to investigate the distribution of (R/S)-albuterol enantiomers
      into skeletal and cardiac muscle. Initially oral dosing was undertaken in
      neonatal mice administered a maximum tolerable dose of racemic albuterol. An in
      vivo infusion rat model was employed for the investigation of albuterol uptake
      into skeletal and cardiac muscle over 4 h. Tissue concentrations were determined
      using liquid chromatography-tandem mass spectrometry (LC-MS/MS). From the oral
      dosing model, mean (+/-SD) levels of racemic albuterol after 5 days were 915 (+/
      293) ng/mL in plasma, 2574 (+/-196) ng/g in muscle, and 53 (+/-6.6) ng/g in brain
      with enantioselective partitioning (muscle:plasma ratio of 5.7 and 1.7 for R- and
      S-albuterol, respectively). In the infusion model, enantioselective disposition
      was observed in skeletal muscle (muscle:plasma ratio of 1.2-1.7 and 0.6-0.7 for R
      and S-albuterol, respectively) and in cardiac muscle (4.1 and 0.5,
      respectively). In conclusion, there is greater partitioning of active (R)
      albuterol than inactive (S)-albuterol into both skeletal and cardiac muscle
      compared to plasma. These findings have relevance for albuterol sports doping,
      cardiac effects, and therapeutic use in muscle wasting diseases. Furthermore, the
      greater muscle partitioning of the active R-albuterol, and the availability of
      pure R-albuterol formulations highlight shortcomings in doping control measures
      using non-enantioselective assays.

PMID- 24574330
TI  - Modulation of circulating protein biomarkers following TRC105 (anti-endoglin
      antibody) treatment in patients with advanced cancer.
AB  - TRC105 is an endoglin-targeting drug that possesses anti-angiogenic and antitumor
      potential. Analysis of the initial phase I trial of TRC105 demonstrated good
      tolerability and efficacy in cancer patients. In this report, we analyzed
      multiple circulating biomarkers at baseline, cycle 2 day 1 (C2D1), and end of
      study (EOS) for each patient. The baseline level and the fold change from
      baseline to both C2D1 and EOS for each marker were statistically analyzed. At
      C2D1, seven markers were significantly downregulated (angiopoietin-2 [Ang-2],
      insulin-like growth factor-binding protein-3 [IGFBP-3], plasminogen activator
      inhibitor-1 [PAI-1] total, platelet-derived growth factor [PDGF]-AA, PDGF-BB,
      thrombospondin-1 [TSP-1], and vascular endothelial growth factor [VEGF]-D).
      Meanwhile, seven markers were upregulated by C2D1 (E-Cadherin, soluble Endoglin
      [sEnd], E-Selectin, interleukin-6 [IL-6], osteopontin [OPN], TSP-2, and von
      Willebrand factor [vWF]). At EOS, seven markers were upregulated including Ang-2,
      C-reactive protein (CRP), intercellular adhesion molecule-1 (ICAM-1), IGFBP-1, IL
      6, TSP-2, and vascular cell adhesion molecule-1 (VCAM-1). A statistical trend was
      also seen for increases of VEGF-A and placenta growth factor (PlGF) at EOS.
      Throughout treatment, sEnd levels significantly increased, an observation that
      was recapitulated in cultured endothelial cells. This is the first report of
      plasma-based biomarkers in patients receiving TRC105. TRC105 treatment by C2D1
      was associated with decreases in several angiogenic factors, including Ang-2,
      PDGF isoforms, and VEGF isoforms, offering insight into the mechanisms underlying
      TRC105's anti-angiogenic, antitumor function. Increases in sEnd were the most
      significant of all observed biomarker changes and may reflect direct drug
      effects. Additionally, biomarker changes in response to TRC105 are distinct from
      those seen in patients treated with VEGF-targeting drugs, suggesting the possible
      utility of combining these two classes of angiogenesis inhibitors in patients.

PMID- 24574332
TI  - Distance dependence of bidirectional concerted proton-electron transfer in phenol
      Ru(2,2'-bipyridine)3(2+) dyads.
AB  - Proton-coupled electron transfer (PCET) was investigated in three covalent donor
      bridge-acceptor molecules with different bridge lengths. Upon photoexcitation of
      their Ru(bpy)3(2+) (bpy=2,2'-bipyridine) photosensitizer in acetonitrile,
      intramolecular long-range electron transfer from a phenolic unit to Ru(bpy)3(2+)
      occurs in concert with release of the phenolic proton to pyrrolidine base. The
      kinetics of this bidirectional concerted proton-electron transfer (CPET) reaction
      were studied as a function of phenol-Ru(bpy)3(2+) distance by increasing the
      number of bridging p-xylene units. A distance decay constant (beta) of 0.67+/
      0.23 A(-1) was determined. The distance dependence of the rates for CPET is thus
      not significantly steeper than that for ordinary (i.e., not proton coupled)
      electron transfer across the same bridges, despite the concerted motion of
      oppositely charged particles into different directions. Long-range bidirectional
      CPET is an important reaction in many proteins and plays a key role in
      photosynthesis; our results are relevant in the context of photoinduced
      separation of protons and electrons as a means of light-to-chemical energy
      conversion. This is the first determination of beta for a bidirectional CPET
      reaction.

PMID- 24574333
TI  - Epigenome-wide scan identifies a treatment-responsive pattern of altered DNA
      methylation among cytoskeletal remodeling genes in monocytes and CD4+ T cells
      from patients with Behcet's disease.
AB  - OBJECTIVE: The pathogenesis of Behcet's disease (BD), an inflammatory disease
      with multisystem involvement, remains poorly understood. This study was
      undertaken to investigate whether there are DNA methylation abnormalities in BD
      that might contribute to the pathogenesis of the disease. METHODS: We examined
      genome-wide DNA methylation patterns in monocytes and CD4+ T cells from 16 male
      patients with untreated BD and age, sex, and ethnicity-matched healthy controls.
      Additional samples were collected from 12 of the same BD patients after treatment
      and achievement of disease remission. Genome-wide DNA methylation patterns were
      assessed using the Infinium HumanMethylation450 BeadChip array, which includes
      >485,000 individual methylation sites across the genome. RESULTS: We identified
      383 CpG sites in monocytes, and 125 in CD4+ T cells, that were differentially
      methylated between BD patients and controls. Bioinformatic analysis revealed a
      pattern of aberrant DNA methylation among genes that regulate cytoskeletal
      dynamics, suggesting that aberrant DNA methylation of multiple classes of
      structural and regulatory proteins of the cytoskeleton might contribute to the
      pathogenesis of BD. Further, treatment of BD modified the differences in DNA
      methylation observed in patients compared to controls; indeed, among CpG sites
      that were differentially methylated after disease remission versus before
      treatment, there was widespread reversal of the direction of aberrant DNA
      methylation observed between the patient and control groups. CONCLUSION: The
      results of this epigenome-wide study-the first such study in BD-provide strong
      evidence that epigenetic modification of cytoskeletal dynamics underlies the
      pathogenesis of BD and its response to treatment.

PMID- 24574335
TI  - A highly active and magnetically recoverable tris(triazolyl)-Cu(I) catalyst for
      alkyne-azide cycloaddition reactions.
AB  - Nanoparticle-supported tris(triazolyl)-CuBr, with a diameter of approximately 25
      nm measured by TEM spectroscopy, has been easily prepared, and its catalytic
      activity was evaluated in the copper-catalyzed azide-alkyne cycloaddition (CuAAC)
      reaction. In initial experiments, 0.5 mol % loading successfully promoted the
      CuAAC reaction between benzyl azide and phenylacetylene, in water at room
      temperature (25  degrees C). During this process, the iron oxide nanoparticle
      supported tris(triazolyl)-CuBr displayed good monodispersity, excellent
      recoverability, and outstanding reusability. Indeed, it was simply collected and
      separated from the reaction medium by using an external magnet, then used for
      another five catalytic cycles without significant loss of catalytic activity.
      Inductively coupled plasma (ICP) analysis for the first cycle revealed that the
      amount of copper leached from the catalyst into the reaction medium is negligible
      (1.5 ppm). The substrate scope has been examined, and it was found that the
      procedure can be successfully extended to various organic azides and alkynes and
      can also be applied to the one-pot synthesis of triazoles, through a cascade
      reaction involving benzyl bromides, alkynes, and sodium azide. In addition, the
      catalyst was shown to be an efficient CuAAC catalyst for the synthesis of allyl-
      and TEG-ended (TEG=triethylene glycol) 27-branch dendrimers. 

PMID- 24574334
TI  - Phase II trial of sorafenib and erlotinib in advanced pancreatic cancer.
AB  - This trial was designed to assess efficacy and safety of erlotinib with sorafenib
      in the treatment of patients with advanced pancreatic adenocarcinoma. An
      exploratory correlative study analyzing pretreatment serum samples using a
      multivariate protein mass spectrometry-based test (VeriStrat(r)), previously
      shown to correlate with outcomes in lung cancer patients treated with erlotinib,
      was performed. Patients received sorafenib 400 mg daily along with erlotinib 150
      mg daily with a primary endpoint of 8-week progression free survival (PFS) rate.
      Pretreatment serum sample analysis by VeriStrat was done blinded to clinical and
      outcome data; the endpoints were PFS and overall survival (OS). Difference
      between groups (by VeriStrat classification) was assessed using log-rank P
      values; hazard ratios (HR) were obtained from Cox proportional hazards model.
      Thirty-six patients received study drug and were included in the survival
      analysis. Eight-week PFS rate of 46% (95% confidence interval (CI): 0.32-0.67)
      did not meet the primary endpoint of a rate >=70%. Thirty-two patients were
      included in the correlative analysis, and VeriStrat "Good" patients had superior
      PFS (HR = 0.18, 95% CI: 0.06-0.57; P = 0.001) and OS (HR = 0.31 95% CI: 0.13
      0.77, P = 0.008) compared to VeriStrat "Poor" patients. Grade 3 toxicities of
      this regimen included fever, anemia, diarrhea, dehydration, rash, and altered
      liver function. This study did not meet the primary endpoint, and this
      combination will not be further pursued. In this small retrospective analysis,
      the proteomic classification was significantly associated with clinical outcomes
      and is being further evaluated in ongoing studies.

PMID- 24574336
TI  - Demystifying disease, democratizing health care.

PMID- 24574338
TI  - Swimming against the tide: drugs drive neutrophil reverse migration.

PMID- 24574339
TI  - beta-Catenin promotes colitis and colon cancer through imprinting of
      proinflammatory properties in T cells.
AB  - The density and type of lymphocytes that infiltrate colon tumors are predictive
      of the clinical outcome of colon cancer. High densities of T helper 17 (T(H)17)
      cells and inflammation predict poor outcome, whereas infiltration by T regulatory
      cells (Tregs) that naturally suppress inflammation is associated with longer
      patient survival. However, the role of Tregs in cancer remains controversial. We
      recently reported that Tregs in colon cancer patients can become proinflammatory
      and tumor-promoting. These properties were directly linked with their expression
      of RORgammat (retinoic acid-related orphan receptor-gammat), the signature
      transcription factor of T(H)17 cells. We report that Wnt/beta-catenin signaling
      in T cells promotes expression of RORgammat. Expression of beta-catenin was
      elevated in T cells, including Tregs, of patients with colon cancer. Genetically
      engineered activation of beta-catenin in mouse T cells resulted in enhanced
      chromatin accessibility in the proximity of T cell factor-1 (Tcf-1) binding sites
      genome-wide, induced expression of T(H)17 signature genes including RORgammat,
      and promoted T(H)17-mediated inflammation. Strikingly, the mice had inflammation
      of small intestine and colon and developed lesions indistinguishable from colitis
      induced cancer. Activation of beta-catenin only in Tregs was sufficient to
      produce inflammation and initiate cancer. On the basis of these findings, we
      conclude that activation of Wnt/beta-catenin signaling in effector T cells and/or
      Tregs is causatively linked with the imprinting of proinflammatory properties and
      the promotion of colon cancer.

PMID- 24574341
TI  - Targeting miR-21 to treat psoriasis.
AB  - Psoriasis is a common inflammatory skin disease with limited treatment options
      that is characterized by a complex interplay between keratinocytes, immune cells,
      and inflammatory mediators. MicroRNAs (miRNAs) are regulators of gene expression
      and play critical roles in many human diseases. A number of miRNAs have been
      described to be up-regulated in psoriasis, but their causal contribution to
      disease development has not been demonstrated. We confirm that miR-21 expression
      is increased in epidermal lesions of patients with psoriasis and that this leads
      to reduced epidermal TIMP-3 (tissue inhibitor of matrix metalloproteinase 3)
      expression and activation of TACE (tumor necrosis factor-alpha-converting
      enzyme)/ADAM17 (a disintegrin and metalloproteinase 17). Using patient-derived
      skin samples and mouse models of psoriasis, we demonstrate that increased miR-21
      may be a consequence of impaired transcriptional activity of Jun/activating
      protein 1 (AP-1), leading to activation of the interleukin-6 (IL-6)/signal
      transducer and activator of transcription 3 (Stat3) pathway. Inhibition of miR-21
      by locked nucleic acid (LNA)-modified anti-miR-21 compounds ameliorated disease
      pathology in patient-derived psoriatic skin xenotransplants in mice and in a
      psoriasis-like mouse model. Targeting miR-21 may represent a potential
      therapeutic option for the treatment of psoriasis. 

PMID- 24574342
TI  - Adiponectin and bariatric surgery: associations with diabetes and cardiovascular
      disease in the Swedish Obese Subjects Study.
AB  - OBJECTIVE: Adiponectin has been implicated in the pathogenesis of type 2
      diabetes, but its role for incident diabetes, myocardial infarction, or stroke in
      obesity is unclear. The aim of this study was to analyze the associations between
      systemic levels of adiponectin and the aforementioned outcomes in a population
      with severe obesity at high risk of diabetes and cardiovascular events. RESEARCH
      DESIGN AND METHODS: We measured serum concentrations of total adiponectin in
      3,299 participants of the prospective controlled Swedish Obese Subjects (SOS)
      Study (bariatric surgery group, n = 1,570; control group given usual care, n =
      1,729). Median follow-up periods ranged between 10 and 13 years for different
      outcomes. RESULTS: In models containing both baseline adiponectin and 2-year
      changes in adiponectin, high baseline adiponectin and 2-year increases in
      adiponectin were associated with decreased risk of diabetes and myocardial
      infarction among controls. In the surgery group, the 2-year weight loss was
      paralleled by substantial increase in circulating adiponectin (1,807-1,958 ng/mL
      per 10-kg weight loss). However, neither baseline adiponectin nor 2-year
      increases in adiponectin were associated with risk of diabetes or myocardial
      infarction in the fully adjusted models in the surgery group. No associations
      were found for stroke in either group. CONCLUSIONS: Taken together, baseline
      adiponectin and 2-year changes were associated with incident diabetes and
      myocardial infarction in the control group but not in the surgery group. Baseline
      adiponectin did not predict treatment benefit of bariatric surgery.

PMID- 24574340
TI  - A zebrafish compound screen reveals modulation of neutrophil reverse migration as
      an anti-inflammatory mechanism.
AB  - Diseases of failed inflammation resolution are common and largely incurable.
      Therapeutic induction of inflammation resolution is an attractive strategy to
      bring about healing without increasing susceptibility to infection. However,
      therapeutic targeting of inflammation resolution has been hampered by a lack of
      understanding of the underlying molecular controls. To address this drug
      development challenge, we developed an in vivo screen for proresolution
      therapeutics in a transgenic zebrafish model. Inflammation induced by sterile
      tissue injury was assessed for accelerated resolution in the presence of a
      library of known compounds. Of the molecules with proresolution activity,
      tanshinone IIA, derived from a Chinese medicinal herb, potently induced
      inflammation resolution in vivo both by induction of neutrophil apoptosis and by
      promoting reverse migration of neutrophils. Tanshinone IIA blocked
      proinflammatory signals in vivo, and its effects are conserved in human
      neutrophils, supporting a potential role in treating human inflammation and
      providing compelling evidence of the translational potential of this screening
      strategy. 

PMID- 24574343
TI  - Heart rate-corrected QT interval is an independent predictor of all-cause and
      cardiovascular mortality in individuals with type 2 diabetes: the Diabetes Heart
      Study.
AB  - OBJECTIVE: Heart rate-corrected QT (QTc) interval is associated with mortality in
      the general population, but this association is less clear in individuals with
      type 2 diabetes. We assessed the association of QTc interval with all-cause and
      cardiovascular disease (CVD) mortality in the Diabetes Heart Study. RESEARCH
      DESIGN AND METHODS: We studied 1,020 participants with type 2 diabetes (83%
      European Americans; 55% women; mean age 61.4 years) who were free of atrial
      fibrillation, major ventricular conduction defects, and antiarrhythmic therapy at
      baseline. QT duration was automatically calculated from a standard 12-lead
      electrocardiogram (ECG). Following American Heart Association/American College of
      Cardiology Foundation recommendations, a linear scale was used to correct the QT
      for heart rate. Using Cox regression, risk was estimated per 1-SD increase in QTc
      interval as well as prolonged QTc interval (>450 ms) vs. normal QTc interval for
      mortality. RESULTS: At baseline, the mean (SD) QTc duration was 414.9 ms (18.1),
      and 3.0% of participants had prolonged QTc. After a median follow-up time of 8.5
      years (maximum follow-up time 13.9 years), 204 participants were deceased. In
      adjusted multivariate models, a 1-SD increase in QTc interval was associated with
      an 18% higher risk for all-cause mortality (hazard ratio 1.18 [95% CI 1.03-1.36])
      and 29% increased risk for CVD mortality (1.29 [1.05-1.59]). Similar results were
      obtained when QTc interval was used as a categorical variable (prolonged vs.
      normal) (all-cause mortality 1.73 [0.95-3.15]; CVD mortality 2.86 [1.35-6.08]).
      CONCLUSIONS: Heart rate QTc interval is an independent predictor of all-cause and
      CVD mortality in this population with type 2 diabetes, suggesting that additional
      prognostic information may be available from this simple ECG measure.

PMID- 24574344
TI  - Migratory activity of circulating mononuclear cells is associated with
      cardiovascular mortality in type 2 diabetic patients with critical limb ischemia.
AB  - OBJECTIVE: Prediction of clinical outcome in diabetic patients with critical limb
      ischemia (CLI) is unsatisfactory. This prospective study investigates if the
      abundance and migratory activity of a subpopulation of circulating mononuclear
      cells, namely, CD45(dim)CD34(pos)CXCR4(pos)KDR(pos) cells, predict major
      amputation and cardiovascular death in type 2 diabetic patients undergoing
      percutaneous transluminal angioplasty for CLI. RESEARCH DESIGN AND METHODS: A
      consecutive series of 119 type 2 diabetic patients with CLI was enrolled.
      CD45(dim)CD34(pos)CXCR4(pos)KDR(pos) cells were assessed by flow cytometry upon
      isolation and also after spontaneous or stromal cell-derived factor 1alpha
      directed migration in an in vitro assay. The association between basal cell
      counts and migratory activity and the risk of an event at 18-month follow-up was
      evaluated in a multivariable regression analysis. RESULTS: Time-to-event analysis
      of amputation (n = 13) showed no association with the candidate predictors.
      Sixteen cardiovascular deaths occurred during 18 months of follow-up. Abundance
      of CD45(dim)CD34(pos)CXCR4(pos)KDR(pos) cells was not associated with
      cardiovascular mortality. Interestingly, in vitro migration of
      CD45(dim)CD34(pos)CXCR4(pos)KDR(pos) cells was higher in patients with
      cardiovascular death compared with event-free subjects (percentage of migrated
      cells median value and interquartile range, 0.03 [0.02-0.07] vs. 0.01 [0.01
      0.03]; P = 0.0095). Multivariable regression model analysis showed that cell
      migration forecasts cardiovascular mortality independently of other validated
      predictors, such as age, diagnosed coronary artery disease, serum C-reactive
      protein, and estimated glomerular filtration rate. In this model, doubling of
      migrated cell counts increases the cardiovascular death hazard by 100% (P <
      0.0001). CONCLUSIONS: The new predictor could aid in the identification of high
      risk patients with type 2 diabetes requiring special diagnostic and therapeutic
      care after revascularization.

PMID- 24574346
TI  - Glycation of apolipoprotein C1 impairs its CETP inhibitory property:
      pathophysiological relevance in patients with type 1 and type 2 diabetes.
AB  - OBJECTIVE Apolipoprotein (apo)C1 is a potent physiological inhibitor of
      cholesteryl ester transfer protein (CETP). ApoC1 operates through its ability to
      modify the electrostatic charge at the lipoprotein surface. We aimed to determine
      whether the inhibitory ability of apoC1 is still effective in vivo in patients
      with diabetes and whether in vitro glycation of apoC1 influences its
      electrostatic charge and its CETP inhibitory effect. RESEARCH DESIGN AND METHODS
      ApoC1 concentrations and CETP activity were measured in 70 type 1 diabetic (T1D)
      patients, 113 patients with type 2 diabetes, and 83 control subjects. The
      consequences of in vitro glycation by methylglyoxal on the electrostatic
      properties of apoC1 and on its inhibitory effect on CETP activity were studied.
      An isoelectric analysis of apoC1 was performed in patients with T1D and in
      normolipidemic-normoglycemic subjects. RESULTS An independent negative
      correlation was found between CETP activity and apoC1 in control subjects but not
      in patients with diabetes. HbA1c was independently associated with CETP activity
      in T1D patients. In vitro glycation of apoC1 modified its electrostatic charge
      and abrogated its ability to inhibit CETP activity in a concentration-dependent
      manner. The isoelectric point of apoC1 in T1D patients was significantly lower
      than that in control subjects. CONCLUSIONS The ability of apoC1 to inhibit CETP
      activity is impaired in patients with diabetes. Glycation of apoC1 leads to a
      change in its electrostatic properties that might account, at least in part, for
      a loss of constitutive CETP inhibition and an increase in plasma CETP activity in
      patients with diabetes. 

PMID- 24574345
TI  - Second-line agents for glycemic control for type 2 diabetes: are newer agents
      better?
AB  - OBJECTIVE: While metformin is generally accepted as the first-line agent in
      treatment of type 2 diabetes, there are insufficient evidence and extensive
      debate about the best second-line agent. We aimed to assess the benefits and
      harms of four commonly used antihyperglycemia treatment regimens considering
      clinical effectiveness, quality of life, and cost. RESEARCH DESIGN AND METHODS:
      We developed and validated a new population-based glycemic control Markov model
      that simulates natural variation in HbA1c progression. The model was calibrated
      using a U.S. data set of privately insured individuals diagnosed with type 2
      diabetes. We compared treatment intensification of metformin monotherapy with
      sulfonylurea, dipeptidyl peptidase-4 inhibitor, glucagon-like peptide-1 receptor
      agonist, or insulin. Outcome measures included life-years (LYs), quality-adjusted
      life-years (QALYs), mean time to insulin dependence, and expected medication cost
      per QALY from diagnosis to first diabetes complication (ischemic heart disease,
      myocardial infarction, congestive heart failure, stroke, blindness, renal
      failure, amputation) or death. RESULTS: According to our model, all regimens
      resulted in similar LYs and QALYs regardless of glycemic control goal, but the
      regimen with sulfonylurea incurred significantly lower cost per QALY and resulted
      in the longest time to insulin dependence. An HbA1c goal of 7% (53 mmol/mol)
      produced higher QALYs compared with a goal of 8% (64 mmol/mol) for all regimens.
      CONCLUSIONS: Use of sulfonylurea as second-line therapy for type 2 diabetes
      generated glycemic control and QALYs comparable with those associated with other
      agents but at lower cost. A model that incorporates HbA1c and diabetes
      complications can serve as a useful clinical decision tool for selection of
      treatment options.

PMID- 24574347
TI  - Predictors of metabolically healthy obesity in children.
AB  - OBJECTIVE: To determine the prevalence of metabolically healthy obesity (MHO) in
      children and examine the demographic, adiposity, and lifestyle predictors of MHO
      status. RESEARCH DESIGN AND METHODS: This cross-sectional study included 8-17
      year olds with a BMI >=85th percentile who were enrolled in a multidisciplinary
      pediatric weight management clinic from 2005-2010. Demographic, anthropometric,
      lifestyle, and cardiometabolic data were retrieved by retrospective medical
      record review. Participants were dichotomized as either MHO or metabolically
      unhealthy obese (MUO) according to two separate classification systems based on:
      1) insulin resistance (IR) and 2) cardiometabolic risk (CR) factors (blood
      pressure, serum lipids, and glucose). Multivariable logistic regression was used
      to determine predictors of MHO using odds ratios (ORs) with 95% CIs. RESULTS: The
      prevalence of MHO-IR was 31.5% (n = 57 of 181) and MHO-CR was 21.5% (n = 39 of
      181). Waist circumference (OR 0.33 [95% CI 0.18-0.59]; P = 0.0002) and dietary
      fat intake (OR 0.56 [95% CI 0.31-0.95]; P = 0.04) were independent predictors of
      MHO-IR; moderate-to-vigorous physical activity (OR 1.80 [95% CI 1.24-2.62]; P =
      0.002) was the strongest independent predictor of MHO-CR. CONCLUSIONS: Up to one
      in three children with obesity can be classified as MHO. Depending on the
      definition, adiposity and lifestyle behaviors both play important roles in
      predicting MHO status. These findings can inform for whom health services for
      managing pediatric obesity should be prioritized, especially in circumstances
      when boys and girls present with CR factors.

PMID- 24574348
TI  - Cardiovascular risk profile in subjects with prediabetes and new-onset type 2
      diabetes identified by HbA(1c) according to American Diabetes Association
      criteria.
AB  - OBJECTIVE: We investigated the cardiovascular risk profile in subjects with
      prediabetes and new-onset type 2 diabetes identified by glycated hemoglobin A1c
      (HbA(1c)) according to the new American Diabetes Association criteria. RESEARCH
      DESIGN AND METHODS: Arterial stiffness, intima-media thickness (IMT), soluble
      receptor for advanced glycation end products (sRAGEs), and oral glucose tolerance
      test (OGTT) were evaluated in 274 subjects without a previous history of
      diabetes. The subjects were stratified into three groups according to the HbA(1c)
      levels. RESULTS: The subjects with prediabetes (n = 117, HbA(1c) 5.7-6.4% [39-46
      mmol/mol]) showed a higher augmentation (Aug), augmentation index (AugI), and IMT
      compared with those with lower HbA1c; however, these values were similar to those
      of subjects with HbA(1c) >6.5% (48 mmol/mol). When we further analyzed the
      subjects with prediabetes but included only subjects with normal glucose
      tolerance (NT) in the analysis, AugI and IMT still remained significantly higher
      than their levels in control subjects with HbA(1c) <5.7% (39 mmol/mol). After
      multiple regression analyses including several cardiovascular risk factors, only
      HbA(1c), age, and sRAGE were significantly correlated with the IMT, whereas age
      and 1-h postload glucose were the major determinants of AugI. CONCLUSIONS: Our
      data show that subjects with prediabetes according to HbA1c, but with both NT
      according to the OGTT and normal fasting glycemia, have an altered IMT and AugI.
      These data suggest that a simple, reproducible, and less expensive marker such as
      HbA1c may be better able to identify prediabetic subjects at high cardiovascular
      risk compared with fasting glycemia or OGTT alone.

PMID- 24574350
TI  - Age-adjusted diabetes mortality rates vary in local communities in a metropolitan
      area: racial and spatial disparities and correlates.
AB  - OBJECTIVE: Diabetes has held steady as the seventh leading cause of death in the
      U.S. since 2006. While aggregated data provide insights into how the country as a
      whole, or even as states, is faring with respect to diabetes mortality,
      disaggregation provides data that may facilitate targeted interventions and
      community engagement. RESEARCH DESIGN AND METHODS: We analyzed deaths from
      diabetes for residents of Chicago to calculate age-adjusted diabetes mortality
      rates (AADMRs). We calculated AADMRs for Chicago by race/ethnicity and community
      area. We also examined the correlation between AADMR and 1) racial/ethnic
      composition of a community area and 2) median household income. RESULTS: The
      AADMR for Chicago (27.5 per 100,000 population) was significantly higher than the
      national rate (22.5). Within both the U.S. and Chicago, the highest AADMRs were
      found among non-Hispanic blacks, followed by Hispanics, and then non-Hispanic
      whites. Within Chicago, Puerto Ricans displayed the highest AADMR at 45.7,
      compared with 35.0 at the national level. There was a strong positive correlation
      between the proportion of black residents in a community area and the AADMR
      (0.64). There was a strong negative relationship between household income and the
      AADMR for the entire city (-0.63) and for the predominantly black community areas
      (-0.52). CONCLUSIONS: These data provide insight into where the worst diabetes
      mortality problems reside in Chicago. Our hope is that these data can be used to
      work toward the development of solutions to the very high diabetes mortality
      rates observed in several communities in Chicago and in similar communities
      throughout the U.S.

PMID- 24574349
TI  - Genetic risk score associations with cardiovascular disease and mortality in the
      Diabetes Heart Study.
AB  - OBJECTIVE Given the high rates of cardiovascular disease (CVD) and associated
      mortality in individuals with type 2 diabetes, identifying and understanding
      predictors of CVD events and mortality could help inform clinical management in
      this high-risk group. Recent large-scale genetic studies may provide additional
      tools in this regard. RESEARCH DESIGN AND METHODS Genetic risk scores (GRSs) were
      constructed in 1,175 self-identified European American (EA) individuals
      comprising the family-based Diabetes Heart Study based on 1) 13 single nucleotide
      polymorphisms (SNPs) and 2) 30 SNPs with previously documented associations with
      CVD in genome-wide association studies. Associations between each GRS and a self
      reported history of CVD, coronary artery calcified plaque (CAC) determined by
      noncontrast computed tomography scan, all-cause mortality, and CVD mortality were
      examined using marginal models with generalized estimating equations and Cox
      proportional hazards models. RESULTS The weighted 13-SNP GRS was associated with
      prior CVD (odds ratio [OR] 1.51 [95% CI 1.22-1.86]; P = 0.0002), CAC (beta
      coefficient [beta] 0.22 [0.02-0.43]; P = 0.04) and CVD mortality (hazard ratio
      [HR] 1.35 [1.10-1.81]; P = 0.04) when adjusting for the other known CVD risk
      factors: age, sex, type 2 diabetes affection status, BMI, current smoking status,
      hypertension, and dyslipidemia. The weighted 30-SNP GRS was also associated with
      prior CVD (OR 1.33 [1.08-1.65]; P = 0.008), CAC (beta 0.29 [0.08-0.50]; P =
      0.006), all-cause mortality (HR 1.28 [1.05-1.56]; P = 0.01), and CVD mortality
      (HR 1.46 [1.08-1.96]; P = 0.01). CONCLUSIONS These findings support the utility
      of two simple GRSs in examining genetic associations for adverse outcomes in EAs
      with type 2 diabetes. 

PMID- 24574351
TI  - Systolic and diastolic abnormalities reduce the cardiac response to exercise in
      adolescents with type 2 diabetes.
AB  - OBJECTIVE: To better understand the cardiac limitations during exercise in
      adolescents with type 2 diabetes mellitus (T2DM), we measured left ventricular
      performance with magnetic resonance imaging (MRI) during exercise in diabetic and
      nondiabetic adolescents. RESEARCH DESIGN AND METHODS: Thirteen subjects with
      T2DM, 27 overweight/obese nondiabetic (ObeseND) subjects, and 19 nondiabetic
      nonobese control subjects were recruited. Cardiac (left ventricular) MRI scans
      were performed at rest and during submaximal exercise. RESULTS: Vo2 peak indexed
      to fat-free mass was reduced in T2DM and ObeseND subjects compared with control
      subjects (P < 0.0001). Indexed cardiac output increased less during exercise and
      was 20% lower in T2DM subjects due to reduced stroke volume. This was a
      consequence of reduced ventricular filling with smaller end-diastolic volume,
      which decreased further during exercise in T2DM subjects, but not in ObeseND or
      control subjects. End-systolic volume was also smaller in T2DM subjects. These
      changes were associated with increased resting and exercise diastolic blood
      pressure, and total peripheral resistance in T2DM subjects. CONCLUSIONS:
      Independently of obesity, T2DM impairs cardiac function during exercise in
      adolescents.

PMID- 24574353
TI  - Does the prevailing hypothesis that small-fiber dysfunction precedes large-fiber
      dysfunction apply to type 1 diabetic patients?
AB  - OBJECTIVE: The prevailing hypothesis that early subclinical small-fiber injury
      precedes large-fiber damage in diabetic sensorimotor polyneuropathy (DSP) is
      based on lower intraepithelial nerve fiber density in type 2 prediabetic patients
      despite normal nerve conduction studies (NCSs). We aimed to confirm the same
      hypothesis in type 1 diabetic patients by examining whether: (1) subjects without
      DSP include a spectrum with both normal and abnormal small-fiber measures and (2)
      subjects with DSP have concurrent evidence of abnormal small-fiber measures.
      RESEARCH DESIGN AND METHODS: A healthy control population (n = 53) was used to
      generate threshold values for four small-fiber tests: cooling detection
      thresholds (CDTs), laser Doppler imaging of heat-evoked flare (LDIflare), heart
      rate variability (HRV), and corneal confocal microscopy. Based on NCS results,
      type 1 diabetic patients (n = 131) were dichotomized according to the presence or
      absence of DSP. RESULTS: Threshold values derived from healthy control subjects
      were 26.5  degrees C, 1.4 cm2, 13%, and 12.9 mm/mm2 for CDT, LDIflare, HRV, and
      corneal nerve fiber length, respectively. Among type 1 diabetic patients, 57 of
      131 had evidence of DSP, and 74 of 133 did not. Using abnormality of any small
      fiber test to define small-fiber dysfunction, 55 of 57 (96.5%) DSP patients and
      39 of 74 (52.7%) control subjects without DSP had concurrent small-fiber damage.
      The severity of small-fiber abnormalities worsened with an increasing number of
      NCS abnormalities (ANOVA, P < 0.01). CONCLUSIONS: Our findings in type 1 diabetes
      support the prevailing hypothesis that small-fiber dysfunction occurs early in
      DSP. However, further research is required to determine which combination of
      small-fiber tests is most suitable as a surrogate marker in clinical trials.

PMID- 24574352
TI  - Effects of moderate-to-vigorous intensity physical activity on overnight and next
      day hypoglycemia in active adolescents with type 1 diabetes.
AB  - OBJECTIVE: Physical activity (PA) provides many benefits to adolescents with type
      1 diabetes; however, these individuals tend to have lower fitness and PA levels
      than their disease-free counterparts. The purpose of this study was to examine
      the acute temporal associations between moderate-to-vigorous intensity PA (MVPA)
      and hypoglycemia (continuous glucose monitor [CGM] reading <=70 mg/dL). RESEARCH
      DESIGN AND METHODS: Nineteen participants (53% females) 14-20 years old with type
      1 diabetes were recruited. Participant fitness was evaluated via indirect
      calorimetry using a maximal exercise test; body composition was measured using
      air displacement plethysmography. An accelerometer was worn continuously (3-5
      days) and acceleration data used to estimate MVPA (minutes per day). Blood
      glucose values were simultaneously tracked using CGM. Controlling for sex,
      percent body fat (%BF), fitness, and concurrent MVPA, the likelihood of nighttime
      and next-day hypoglycemia due to MVPA was examined using logistic regression.
      RESULTS: Participants were of average fitness (females: 43.9 mL/kg/min; males:
      49.8 mL/kg/min) and adiposity (females: 26.2%; males: 19.2%); 63.2% met the U.S.
      federal guideline of accumulating 60 min/day of MVPA. Hypoglycemia was 31% more
      likely in those who accumulated 30 min/day more MVPA in the previous afternoon
      than those with less (95% CI 1.05-1.63; P = 0.017). CONCLUSIONS: The results
      suggest that participating in afternoon MVPA increases the risk of overnight and
      next-day hypoglycemia, independent of sex, %BF, fitness, and concurrent MVPA.
      While promoting PA as a healthy behavior, it is important to educate adolescents
      with type 1 diabetes on prevention of hypoglycemia following PA.

PMID- 24574354
TI  - Racial disparity of eye examinations among the U.S. working-age population with
      diabetes: 2002-2009.
AB  - OBJECTIVE: Diabetes care differs across racial and ethnic groups. This study
      aimed to assess the racial disparity of eye examinations among U.S. adults with
      diabetes. RESEARCH DESIGN AND METHODS: Working-age adults (age 18-64 years) with
      diabetes were studied using data from the Medical Expenditure Panel Survey
      Household Component (2002-2009) including the Diabetes Care Survey. Racial and
      ethnic groups were classified as non-Hispanic whites and minorities. People
      reporting one or more dilated eye examination were considered to have received an
      eye examination in a particular year. Eye examination rates were compared between
      racial/ethnic groups for each year, and were weighted to national estimates.
      Multivariate adjusted odds ratios (aORs) and 95% CIs for racial/ethnic difference
      were assessed annually using logistic regression models. Other influencing
      factors associated with eye examination were also explored. RESULTS: Whites had
      consistently higher unadjusted eye examination rates than minority populations
      across all 8 years. The unadjusted rates increased from 56% in 2002 to 59% in
      2009 among whites, while the rates in minorities decreased from 56% in 2002 to
      49% in 2009. The largest significant racial gap of 15% was observed in 2008,
      followed by 11%, 10%, and 7% in 2006, 2009, and 2005, respectively (P < 0.05).
      Minorities were less likely to receive eye examination (2006: aOR 0.75 [95% CI
      0.57-0.99]; 2008: 0.61 [0.45-0.84]). CONCLUSIONS: The racial/ethnic differences
      in eye examinations for patients with diabetes have persisted over the last
      decade. National programs to improve screening and monitoring of diabetic
      retinopathy are needed to target minority populations.

PMID- 24574356
TI  - Association between glycemia and mortality in diabetic individuals on renal
      replacement therapy in the U.K.
AB  - OBJECTIVE: In the U.K., one-third of patients receiving treatment with dialysis
      have diabetes. Guidelines from organizations representing patients with renal
      disease or diabetes advocate tight glycemic control in patients with end-stage
      renal disease, despite glucose-lowering trials having excluded these patients.
      RESEARCH DESIGN AND METHODS: Using national U.K. Renal Registry data, we tested
      whether glycemia as measured by hemoglobin (Hb) A(1c) (HbA(1c)) level is
      associated with death in adults with diabetes starting hemodialysis or peritoneal
      dialysis between 1997 and 2006, and observed for at least 6 months. Of 7,814
      patients, we excluded those who had died within 6 months; had received
      transplants; were lost/recovered; or lacked measures of HbA1c, ethnicity, or Hb.
      Categorizing HbA1c measured in the first 6 months of starting dialysis as <6.5%
      (<48 mmol/mol), 6.5-7.4% (48-57 mmol/mol) (reference value), 7.5-8.4% (58-68
      mmol/mol), and >=8.5% (>=69 mmol/mol), we adjusted in proportional hazards models
      for age, sex, ethnicity, deprivation, year, dialysis type, and Hb, and tested for
      interactions. RESULTS: Of 3,157 patients observed for a median time of 2.7 years,
      1,688 died. For patients >=60 years of age, we found no association between HbA1c
      and death; among younger patients, relative to those with HbA(1c) values 6.5
      7.4%, the hazard ratio for HbA(1c) level 7.5-8.4% was 1.2 (95% CI 0.9-1.5), and
      for HbA(1c) level >8.5% was 1.5 (1.2-1.9). The projected difference in median
      survival time between younger patients with a reference HbA1c value versus >8.5%
      was 1 year. CONCLUSIONS: In the absence of trials, and confounding
      notwithstanding, these observational data support improved glycemic control in
      younger patients prior to and during dialysis.

PMID- 24574355
TI  - The association of basal insulin glargine and/or n-3 fatty acids with incident
      cancers in patients with dysglycemia.
AB  - OBJECTIVE Epidemiologic studies linking insulin glargine and glucose-lowering
      therapies to cancers and n-3 fatty acids to cancer prevention have not been
      confirmed. We aimed to assess the effect of insulin glargine and n-3 fatty acids
      on incident cancers within the context of the ORIGIN (Outcome Reduction with
      Initial Glargine Intervention) trial. RESEARCH DESIGN AND METHODS The ORIGIN
      trial is an international, long-term, randomized two-by-two factorial study
      comparing insulin glargine with standard care and n-3 fatty acids with placebo
      (double blind) in people with dysglycemia at high risk for cardiovascular events.
      The primary outcome measure (cancer substudy) was the occurrence of any new or
      recurrent adjudicated cancer. Cancer mortality and cancer subtypes were also
      analyzed. RESULTS Among 12,537 people (mean age 63.5 years, SD 7.8; 4,388
      females), 953 developed a cancer event during the median follow-up of 6.2 years.
      In the glargine and standard care groups, the incidence of cancers was 1.32 and
      1.32 per 100 person-years, respectively (P = 0.97), and in the n-3 fatty acid and
      placebo groups, it was 1.28 and 1.36 per 100 person-years, respectively (P =
      0.39). No difference in the effect of either intervention was noted within
      predefined subgroups (P for all interactions >=0.17). Cancer-related mortality
      and cancer-specific outcomes also did not differ between groups.
      Postrandomization HbA1c levels, glucose-lowering therapies (including metformin),
      and BMI did not affect cancer outcomes. CONCLUSIONS Insulin glargine and n-3
      fatty acids have a neutral association with overall and cancer-specific outcomes,
      including cancer-specific mortality. Exposure to glucose-lowering therapies,
      including metformin, and HbA1c level during the study did not alter cancer risk. 

PMID- 24574357
TI  - Risk-stratified patients with resectable soft tissue sarcoma benefit from
      epirubicin-based adjuvant chemotherapy.
AB  - As adjuvant chemotherapy (AC) for soft tissue sarcomas is controversial, we
      performed a retrospective analysis of patients seen at Washington University in
      St. Louis to evaluate whether it benefited our patient population. Patients were
      risk-assessed using the Memorial Sloan Kettering Predictive Nomogram (MSKPN). We
      defined high-risk patients by a MSKPN 4-year postoperative probability of sarcoma
      specific death of >=0.3 and investigated if they benefited from AC. Retrospective
      review was performed on patients seen between 15 February 1996 and 6 February
      2010. A propensity score method in the logistic regression framework was used to
      model the likelihood of receiving AC. To make causal inference on the effect of
      AC on survival outcomes, a propensity score inverse probability of treatment
      weighting approach was applied to survival analysis. Overall, 135 high-grade
      patients were assessed, 33 were treated with Ifosfamide/Epirubicin (I/Epi) and
      102 were non AC patients. The stratified MSKPN risk was not significantly
      associated with any survival endpoint in the whole cohort, but trended for
      overall survival (OS) when evaluated against non AC patients. After adjustment
      for MSKPN risk and other variables, patients not receiving chemotherapy had
      significantly worse OS, recurrent free survival, and disease-specific survival
      (DSS) with adjusted hazard ratios of 4.18 (95% CI: 2.22-7.90), 8.96 (95% CI: 3.85
      20.83), and 5.42 (95% CI: 2.09-14.06), respectively. In retrospective analyses,
      risk-stratified patients with soft tissue sarcoma benefited from I/Epi-based AC.
      Randomized I/Epi versus I/Doxorubicin clinical trials may determine the optimal
      adjuvant treatment. 

PMID- 24574358
TI  - A membraneless glucose/O(2) biofuel cell based on Pd aerogels.
AB  - In this study, we introduce the first membraneless glucose/O2 biofuel cell using
      Pd-based aerogels as electrode materials. The bioanode was fabricated with a
      coimmobilized mediator and glucose oxidase for the oxidation of glucose, in which
      ferrocenecarboxylic acid was integrated into a three-dimensional porous beta
      cyclodextrin-modified Pd aerogel to mediate the bioelectrocatalytic reaction.
      Bilirubin oxidase and Pd-Pt alloy aerogel were confined to an electrode surface,
      which realized the direct bioelectrocatalytic function for the reduction of O2 to
      H2 O with a synergetic effect at the biocathode. By employing these two
      bioelectrodes, the assembled glucose/O2 biofuel cell showed a maximum power
      output of 20 MUW cm(-2) at 0.25 V. 

PMID- 24574359
TI  - Response assessment of NovoTTF-100A versus best physician's choice chemotherapy
      in recurrent glioblastoma.
AB  - The NovoTTF-100A device emits frequency-tuned alternating electric fields that
      interfere with tumor cell mitosis. In phase III trial for recurrent
      glioblastomas, NovoTTF-100A was shown to have equivalent efficacy and less
      toxicity when compared to Best Physician's Choice (BPC) chemotherapy. We analyzed
      the characteristics of responders and nonresponders in both cohorts to determine
      the characteristics of response and potential predictive factors. Tumor response
      and progression were determined by Macdonald criteria. Time to response, response
      duration, progression-free survival (PFS) +/- Simon-Makuch correction, overall
      survival (OS), prognostic factors, and relative hazard rates were compared
      between responders and nonresponders. Median response duration was 7.3 versus 5.6
      months for NovoTTF-100A and BPC chemotherapy, respectively (P = 0.0009). Five of
      14 NovoTTF-100A responders but none of seven BPC responders had prior low-grade
      histology. Mean cumulative dexamethasone dose was 35.9 mg for responders versus
      485.6 mg for nonresponders in the NovoTTF-100A cohort (P < 0.0001). Hazard
      analysis showed delayed tumor progression in responders compared to
      nonresponders. Simon-Makuch-adjusted PFS was longer in responders than in
      nonresponders treated with NovoTTF-100A (P = 0.0007) or BPC chemotherapy (P =
      0.0222). Median OS was longer for responders than nonresponders treated with
      NovoTTF-100A (P < 0.0001) and BPC chemotherapy (P = 0.0235). Pearson analysis
      showed strong correlation between response and OS in NovoTTF-100A (P = 0.0002)
      but not in BPC cohort (P = 0.2900). Our results indicate that the response
      characteristics favor NovoTTF-100A and data on prior low-grade histology and
      dexamethasone suggest potential genetic and epigenetic determinants of NovoTTF
      100A response.

PMID- 24574360
TI  - Susceptibility-weighted imaging for stem cell visualization in a rat
      photothrombotic cerebral infarction model.
AB  - BACKGROUND: In cell therapy, magnetic resonance imaging (MRI) has been used to
      visualize superparamagnetic iron oxide (SPIO)-labeled stem cells homing to a
      lesion. Improving traceability is to utilize the sequence that maximizes
      sensitivity to the susceptibility effect of SPIO. PURPOSE: To explore the best
      method by comparing the MRI sequences to visualize mesenchymal stem cells (MSCs)
      labeled with SPIO. MATERIAL AND METHODS: Human bone marrow (hBM)-derived MSCs
      were labeled by internalization of SPIO nanoparticles. In vitro MRI was performed
      for the SPIO-labeled hBM-MSCs in tubes with T2-weighted (T2W), T2*-weighted
      (T2*W), and susceptibility-weighted images (SWI). Contrast-to-noise ratio (CNR)
      and volumes of dark signal of SPIO-labeled hBM-MSCs were obtained on images of
      each sequence. Photothrombotic cerebral infarction (PTCI) was induced in eight
      rats, and 2.5 * 10(5) SPIO-labeled hBM-MSCs were infused through the tail vein on
      the third day. In vivo MRI of the rat brain was performed using a 3.0 T MRI on
      the first, third, seventh, and 14th days. CNRspio was obtained on T2W imaging,
      T2*W imaging, and SWI. The dark signals were compared with the SPIO-positive
      cells of Prussian blue staining. RESULTS: In vitro MRI of 5 * 10(5) SPIO-labeled
      hBM-MSCs showed the CNR and volume of dark signal to be 63, 517 mm(3) in SWI, 41,
      228 mm(3) in T2*W imaging, and 56, 41 mm(3) in T2W imaging, respectively. In vivo
      MRI showed a dark signal surrounding the high signal intensity of PTCI.
      Pathologically, the dark signals were matched with SPIO-labeled hBM-MSC in the
      corresponding rat. The dark signal was most prominent in SWI, then T2*W imaging,
      and finally in T2W imaging (P <0.05). In SWI, other causes of dark signals were
      matched with the veins and the choroid plexuses on histopathology. CONCLUSION:
      SWI can visualize SPIO-labeled hBM-MSCs more sensitively, earlier, and with
      larger size and greater contrast than T2W imaging and T2*W imaging.

PMID- 24574363
TI  - HFE-associated hereditary hemochromatosis: overview of genetics and clinical
      implications for nurse practitioners in primary care settings.
AB  - PURPOSE: HFE-hemochromatosis is one of the most common genetic disorders in the
      United States among Caucasians of Northern European ancestry. The purpose of this
      article is to discuss HFE-associated hereditary hemochromatosis (HH), including
      the genetics, pathophysiology, phenotype and genotype, diagnostics, and
      management utilizing a case-based format as an exemplar. DATA SOURCES: Online
      genetic resources; professional guidelines; review; and scientific articles.
      CONCLUSION: HFE-HH is an autosomal recessive disorder and two major genes C282Y
      and H63D are associated with HH (iron overload) susceptibility particularly
      C282Y/C282Y mutations. It has a variable penetrance and expression. Individuals
      who develop iron overload may develop broad symptoms, including joint discomfort,
      fatigue, decreased libido, and abdominal pain; and if left untreated, HFE-HH has
      the potential of developing end-organ disease including liver fibrosis,
      cirrhosis, and cancer; cardiac arrhythmias or heart failure; and diabetes.
      Suspicion of the disorder begins with personal and family history, transferrin
      saturation, and ferritin levels, and if high, genotyping to confirm the disorder.
      Management consists of correcting iron overload to prevent/delay end-organ damage
      often consisting of intermittent phlebotomy. IMPLICATIONS FOR PRACTICE: Knowledge
      of HFE-HH is essential so that nurse practitioners can identify individuals at
      risk and to provide appropriate management of care and referral.

PMID- 24574362
TI  - Copy number increase of ACTN4 is a prognostic indicator in salivary gland
      carcinoma.
AB  - Copy number increase (CNI) of ACTN4 has been associated with poor prognosis and
      metastatic phenotypes in various human carcinomas. To identify a novel prognostic
      factor for salivary gland carcinoma, we investigated the copy number of ACTN4. We
      evaluated DNA copy number of ACTN4 in 58 patients with salivary gland carcinoma
      by using fluorescent in situ hybridization (FISH). CNI of ACTN4 was recognized in
      14 of 58 patients (24.1%) with salivary gland carcinoma. The cases with CNI of
      ACTN4 were closely associated with histological grade (P = 0.047) and vascular
      invasion (P = 0.033). The patients with CNI of ACTN4 had a significantly worse
      prognosis than the patients with normal copy number of ACTN4 (P = 0.0005 log-rank
      test). Univariate analysis by the Cox proportional hazards model showed that
      histological grade, vascular invasion, and CNI of ACTN4 were independent risk
      factors for cancer death. Vascular invasion (hazard ratio [HR]: 7.46; 95%
      confidence interval [CI]: 1.98-28.06) and CNI of ACTN4 (HR: 3.23; 95% CI: 1.08
      9.68) remained as risk factors for cancer death in multivariate analysis. Thus,
      CNI of ACTN4 is a novel indicator for an unfavorable outcome in patients with
      salivary gland carcinoma.

PMID- 24574361
TI  - The central molecular clock is robust in the face of behavioural arrhythmia in a
      Drosophila model of Alzheimer's disease.
AB  - Circadian behavioural deficits, including sleep irregularity and restlessness in
      the evening, are a distressing early feature of Alzheimer's disease (AD). We have
      investigated these phenomena by studying the circadian behaviour of transgenic
      Drosophila expressing the amyloid beta peptide (Abeta). We find that Abeta
      expression results in an age-related loss of circadian behavioural rhythms
      despite ongoing normal molecular oscillations in the central clock neurons. Even
      in the absence of any behavioural correlate, the synchronised activity of the
      central clock remains protective, prolonging lifespan, in Abeta flies just as it
      does in control flies. Confocal microscopy and bioluminescence measurements point
      to processes downstream of the molecular clock as the main site of Abeta
      toxicity. In addition, there seems to be significant non-cell-autonomous Abeta
      toxicity resulting in morphological and probably functional signalling deficits
      in central clock neurons. 

PMID- 24574364
TI  - The Experiences of Well-Being of Palliative Care Patients in Malaysia: A Thematic
      Analysis.
AB  - A qualitative study was conducted with semistructured interviews to explore the
      experiences of well-being in 15 adult palliative care inpatients of University
      Malaya Medical Center, Kuala Lumpur, Malaysia. The results were thematically
      analyzed. Six basic themes were generated (1) positive attitude, (2) positive
      cognitions, (3) positive emotions, (4) positive engagement, (5) positive
      relationships, and (6) positive circumstances. The Seeds Model was conceptualized
      from the analysis. This model may inform the development of interventions in the
      enhancement of well-being of palliative care patients. 

PMID- 24574365
TI  - Brief, patient-centred risk-reduction counselling at the time of a rapid HIV test
      does not affect subsequent acquisition of sexually transmitted infections.

PMID- 24574366
TI  - Overenthusiastic stroke risk factor modification in the over-80s: are we being
      disingenuous to ourselves, and to our oldest patients?
AB  - Statins and antihypertensive therapy are widely used in our oldest patients (ie,
      those aged over 80 years). The epidemiology suggests that, by this age,
      hypertension is not an attributable risk factor for stroke, and
      hypercholesterolaemia has little effect on stroke risk overall. The largest
      trials of antihypertensive therapy and statins in this age group show at best a
      marginal clinical reduction in stroke and very modest clinical reductions in
      other cardiovascular end points. Older patients have very diverse views on the
      relative importance of stroke and death as end points, and these differ from
      physicians' views. Informed consent principles (full relevant information in an
      accessible form, and autonomy of decision-making) suggest that these medications
      are greatly over-prescribed in the healthy elderly and largely irrelevant in the
      frail elderly, but require that the patient should be actively involved in the
      process.

PMID- 24574367
TI  - Managing uncomplicated recurrent urinary tract infections in reproductive aged
      women: a primary care approach.
AB  - PURPOSE: Uncomplicated, recurrent urinary tract infections (RUTIs) in heal-thy,
      premenopausal women are a common health complaint. This article discusses risk
      factors, diagnostic techniques, medical management, and referral information to
      help clinicians manage RUTIs in the primary care setting. DATA SOURCES: This
      article cites research articles, systematic reviews, and current guidelines.
      CONCLUSIONS: The majority of RUTIs in healthy premenopausal women can be managed
      by using individualized plans of care. Referrals are usually not useful nor cost
      effective. IMPLICATIONS FOR PRACTICE: This article discusses treatments based on
      increasing antimicrobial resistance and examines nonmicrobial options in RUTI
      prevention. This article serves as a foundation for guiding primary care
      providers in managing this common problem using current research and guidelines.

PMID- 24574368
TI  - DSM-5 bids farewell to hypochondriasis and welcomes somatic symptom disorder and
      illness anxiety disorder.

PMID- 24574369
TI  - Detection of BRAFV600E mutation on papillary thyroid carcinoma and metastatic
      malignant melanoma by fine-needle aspiration cytology: how genetic testing may
      drive toward personalized medicine.
AB  - A genetic link between cutaneous melanoma and thyroid cancer (TC) has been
      identified. A high percentage of both melanomas and papillary carcinomas of the
      thyroid harbors a recurrent mutation (i.e., BRAF(V600E) ) in the BRAF oncogene.
      Herein, we report the case of a 65-year-old man with papillary TC and cutaneous
      malignant melanoma metastatic to masseter muscle, both characterized by BRAF
      mutation. This is one of the rare reports in which a complete molecular
      characterization has been performed. As the patients with papillary thyroid
      carcinoma have a higher risk of malignant melanoma and vice versa, continuous
      monitoring of such patients, with either of these tumors is necessary. Fine
      needle aspiration cytology is useful as shown in the present case.

PMID- 24574371
TI  - Paint it black: and seal with a disk.

PMID- 24574372
TI  - Comparison of two liquid preservatives for SurePathTM slides prepared from voided
      urine.
AB  - Blood-rich gynecologic specimens can be problematic in the processing of liquid
      based cytology. However, little is known about the influence of erythrocytes and
      protein on urine specimens. In addition, the SurePathTM system has two
      preservatives for non-gynecologic specimens. In this study, we compared the
      epithelial cell counts and cytomorphology obtained from CytoRichTM (CR) Red and
      CR Blue. A total of 98 voided urine samples were processed using both CR Red and
      CR Blue. We made an assessment of the epithelial cell counts, fixation, and
      staining quality, and backgrounds of both slides. Urine protein and urine
      erythrocyte counts were analyzed, and those data were compared with the
      epithelial cell counts in CR Red and CR Blue slides. Overall, epithelial cell
      counts were equivalent for both CR Red and CR Blue slides. However, in high-level
      proteinuria cases, the CR Red slides showed higher epithelial cell counts than
      the CR Blue slides. On the other hand, in microscopic hematuria cases, the CR
      Blue slides showed higher epithelial cell counts than the CR Red slides. We have
      found both CR Red and CR Blue to be available for urine cytology. However, it is
      important to note that CR Blue is inferior to CR Red in epithelial cell recovery
      rates in cases of high-level proteinuria.

PMID- 24574370
TI  - Association of exhaled carbon monoxide with subclinical cardiovascular disease
      and their conjoint impact on the incidence of cardiovascular outcomes.
AB  - AIMS: Whereas endogenous carbon monoxide (CO) is cytoprotective at physiologic
      levels, excess CO concentrations are associated with cardiometabolic risk and may
      represent an important marker of progression from subclinical to clinical
      cardiovascular disease (CVD). METHODS AND RESULTS: In 1926 participants of the
      Framingham Offspring Study (aged 57 +/- 10 years, 46% women), we investigated the
      relationship of exhaled CO, a surrogate of blood CO concentration, with both
      prevalent subclinical CVD and incident clinical CVD events. Presence of
      subclinical CVD was determined using a comprehensive panel of diagnostic tests
      used to assess cardiac and vascular structure and function. Individuals with the
      highest (>5 p.p.m.) compared with lowest (<=4 p.p.m.) CO exposure were more
      likely to have subclinical CVD [odds ratios (OR): 1.67, 95% CI: 1.32-2.12; P <
      0.001]. During the follow-up period (mean 5 +/- 3 years), 193 individuals
      developed overt CVD. Individuals with both high CO levels and any baseline
      subclinical CVD developed overt CVD at an almost four-fold higher rate compared
      with those with low CO levels and no subclinical disease (22.1 vs. 6.3%).
      Notably, elevated CO was associated with incident CVD in the presence [hazards
      ration (HR): 1.83, 95% CI: 1.08-3.11; P = 0.026] but not in the absence (HR:
      0.80, 95% CI: 0.42-1.53; P = 0.51) of subclinical CVD (Pinteraction = 0.019).
      Similarly, subclinical CVD was associated with incident CVD in the presence of
      high but not low CO exposure. CONCLUSION: Our findings in a community-based
      sample suggest that elevated CO is a marker of greater subclinical CVD burden
      and, furthermore, a potential key component in the progression from subclinical
      to clinical CVD.

PMID- 24574373
TI  - Cytological features of dedifferentiated adenoid cystic carcinoma of the trachea:
      a case report.
AB  - Adenoid cystic carcinoma (AdCC) is a distinct type of carcinoma, and cytological
      examination has been recognized as a useful tool in its diagnosis.
      Dedifferentiation is defined as the abrupt transformation of a low-grade tumor
      into a tumor with high-grade components. Albeit extremely rare, dedifferentiated
      AdCC has been reported: however, the cytological features of this tumor have not
      been documented. We observed a case in which a 66-year-old Japanese male had
      stenosis and thickness of the lower tracheal and bronchial walls. Cytological
      smears of a bronchial brush specimen revealed features typical for low-grade
      AdCC. However, a few cohesive epithelial cell clusters composed of large,
      atypical polygonal cells with large nuclei and conspicuous nucleoli also were
      present. This component was considered to represent dedifferentiated carcinoma.
      Histopathological study of the resected bronchial tumor revealed dedifferentiated
      AdCC. The cytological diagnosis of conventional low-grade AdCC is straightforward
      in most cases, although extremely rare, dedifferentiated carcinoma can occur
      within the conventional AdCC, and detection of a dedifferentiated component is
      possible in a cytological specimen because of obvious nuclear atypia. Therefore,
      careful observation is needed because cytologic diagnosis of dedifferentiated
      AdCC can help expedite treatment of this highly aggressive tumor.

PMID- 24574374
TI  - Diagnostic benefits and cost-effectiveness of on-site imprint cytology adequacy
      evaluation of core needle biopsies of bone lesions.
AB  - BACKGROUND: Core needle biopsy (CNB) is a well-established, successful technique
      for the diagnosis of various organ system lesions. To increase diagnostic yield,
      on-site cytologic evaluation of adequacy (OCA) is routinely performed at many
      institutions. Numerous studies evaluating the impact of OCA on CNB have been
      published. However, little has been said regarding accuracy of OCA for bone
      lesions. METHODS: To evaluate this, we reviewed our experience during a two-year
      period, and compared OCA results with the final diagnosis of the corresponding
      CNB. For the study, diagnoses were divided into three categories: malignant,
      benign, and nonspecific/nondiagnostic findings. RESULTS: Sixty-one cases were
      included. During OCA, 25 cases were diagnosed as malignant, three cases as
      benign, and 33 as nonspecific/nondiagnostic. On histologic evaluation, 29 cases
      were malignant, 16 were benign, and 16 were classified as
      nonspecific/nondiagnostic. Concordance with final CNB diagnosis was seen in 100%
      of malignant, 67% of benign, and 45% of nonspecific/nondiagnostic on-site
      cytology evaluations. The overall diagnostic success rate of OCA for malignancy
      was 86% (25/29). The success rate of OCA for benign lesions was only 13%. Fifty
      four percent of cases were diagnosed as nonspecific/nondiagnostic on-site. This
      category included four false negative cases. CONCLUSIONS: We conclude that for
      lesions with a suspicion of malignancy, OCA is a valuable adjuvant diagnostic
      tool. However, for cases with a benign or nonspecific clinical impression, OCA
      has a limited diagnostic role. Careful selection of cases in which OCA is
      beneficial is necessary to maintain accuracy and to limit procedure costs.

PMID- 24574375
TI  - Cytologic features of stratified mucin producing intraepithelial lesion of the
      cervix--a case report.
AB  - Stratified mucin-producing intraepithelial lesion (SMILE) of the cervix is a
      human papilloma virus (HPV) associated high grade intraepithelial columnar cell
      neoplasm that is thought to arise from the reserve cells of the transformation
      zone. It is composed of immature stratified cells that display intracytoplasmic
      mucin and is commonly associated with high grade squamous intraepithelial lesion
      (HSIL), adenocarcinoma in situ (AIS), and invasive carcinoma. Here, we describe
      the cytologic features of SMILE and discuss its pitfalls in cervical cytology. A
      51-year-old woman was diagnosed with SMILE on a cervical biopsy. Histologically,
      the dysplastic epithelium showed enlarged nuclei with increased nuclear density
      and presence of mucin-producing columnar cells throughout its thickness. The
      slides from the last two Pap tests (ThinPrep) performed on the patient were
      reviewed and compared with the histology. Cytologically, groups of atypical
      endocervical glandular cells were seen on both Pap tests. These groups showed
      mild nuclear crowding, slightly enlarged nuclei, nuclear hyperchromasia, and
      indistinct nucleoli. The borders of these cell groups were relatively smooth.
      Original cytologic diagnosis was atypical squamous cells of undetermined
      significance (ASC-US) in both instances. HPV (Hybrid Capture 2) testing was
      positive on both occasions. Similar to the histology, cytologic features of SMILE
      are subtle. The features are not typical for AIS or for HSIL and could easily be
      misinterpreted as reactive. This report emphasizes that careful review of crowded
      groups of glandular cells in HPV positive women is absolutely critical. Based on
      our knowledge, this is the first description of the cytologic features of these
      lesions.

PMID- 24574376
TI  - Cytological diagnosis of angiosarcoma arising in an immunosuppressed patient 6
      years after multi-visceral transplantation: a case report and literature review.
AB  - Angiosarcoma is a rare and aggressive malignant tumor of soft tissue. It can
      arise in almost any part of the body, most commonly in the skin and the
      superficial soft tissue in the head and neck region. Although the etiology of
      angiosarcoma is unknown, there are several well-known risk factors, such as
      chronic lymphedema, exposure to radiation, toxins, and foreign bodies. It rarely
      occurs in transplant patients. Cytological criteria for the diagnosis of
      angiosarcoma have not been fully established, having been described only in a few
      cases, mostly fine-needle aspiration biopsies (FNAB). Herein, we present a case
      of angiosarcoma arising in an immunosuppressed patient status post multi-visceral
      transplantation and diagnosed by cytology. To the best of our knowledge, this is
      the first report of such a case in the English literature. The cytological
      findings from endoscopic ultrasound-guided FNAB and ascites fluid are discussed.

PMID- 24574377
TI  - Aspiration cytology of mesenchymal hamartoma of the chest wall: a case report and
      literature review.
AB  - Mesenchymal hamartoma of the chest wall is a rare tumor-like lesion of infancy
      and childhood. The few available descriptions of the findings on fine needle
      aspiration list spindle-shaped cells and cartilage or chondromyxoid material as
      essential features for this diagnosis. An aggressive appearance on imaging
      studies and a lack of familiarity with this lesion, can lead the pathologist to
      misdiagnose the cytologic findings as malignancy. We reported a 5-month-old male
      presenting with a mass of the right chest wall progressively for 2 months.
      Radiologic studies showed a mixed solid and cystic mass originating from the
      third, fourth and fifth ribs, and a diagnosis of malignancy was favored. Fine
      needle aspiration recovered only spindle-shaped cells and a few multinucleated
      giant cells of osteoclast type. After a review of the imaging, a diagnosis of
      mesenchymal hamartoma of the chest wall was raised. This diagnosis was confirmed
      by pathologic examination of the subsequently resected mass. This is the sixth
      report of a mesenchymal hamartoma of the chest wall diagnosed by fine needle
      aspiration. This case illustrates that this diagnosis can be suspected in the
      absence of cartilage or chondromyxoid material, given appropriate clinical and
      radiologic findings.

PMID- 24574378
TI  - Primary melanoma of the urinary bladder identified by urine cytology: a rare case
      report.

PMID- 24574379
TI  - Marking the 'retirement' of Chris Wood from McMaster University.

PMID- 24574380
TI  - Gill cell culture systems as models for aquatic environmental monitoring.
AB  - A vast number of chemicals require environmental safety assessments for market
      authorisation. To ensure acceptable water quality, effluents and natural waters
      are monitored for their potential harmful effects. Tests for market authorisation
      and environmental monitoring usually involve the use of large numbers of
      organisms and, for ethical, cost and logistic reasons, there is a drive to
      develop alternative methods that can predict toxicity to fish without the need to
      expose any animals. There is therefore a great interest in the potential to use
      cultured fish cells in chemical toxicity testing. This review summarises the
      advances made in the area and focuses in particular on a system of cultured fish
      gill cells grown into an epithelium that permits direct treatment with water
      samples. 

PMID- 24574381
TI  - The physiology of fish at low pH: the zebrafish as a model system.
AB  - Ionic regulation and acid-base balance are fundamental to the physiology of
      vertebrates including fish. Acidification of freshwater ecosystems is recognized
      as a global environmental problem, and the physiological responses to acid
      exposure in a few fish species are well characterized. However, the underlying
      mechanisms promoting ionic and acid-base balance for most fish species that have
      been investigated remain unclear. Zebrafish (Danio rerio) has emerged as a
      powerful model system to elucidate the molecular basis of ionic and acid-base
      regulation. The utility of zebrafish is related to the ease with which it can be
      genetically manipulated, its suitability for state-of-the-art molecular and
      cellular approaches, and its tolerance to diverse environmental conditions.
      Recent studies have identified several key regulatory mechanisms enabling
      acclimation of zebrafish to acidic environments, including activation of the
      sodium/hydrogen exchanger (NHE) and H(+)-ATPase for acid secretion and Na(+)
      uptake, cortisol-mediated regulation of transcellular and paracellular Na(+)
      movements, and ionocyte proliferation controlled by specific cell-fate
      transcription factors. These integrated physiological responses ultimately
      contribute to ionic and acid-base homeostasis in zebrafish exposed to acidic
      water. In the present review, we provide an overview of the general effects of
      acid exposure on freshwater fish, the adaptive mechanisms promoting extreme acid
      tolerance in fishes native to acidic environments, and the mechanisms regulating
      ionic and acid-base balance during acid exposure in zebrafish. 

PMID- 24574383
TI  - Ontogeny of O2 and CO2//H+ chemosensitivity in adrenal chromaffin cells: role of
      innervation.
AB  - The adrenal medulla plays a key role in the physiological responses of developing
      and mature mammals by releasing catecholamines (CAT) during stress. In rodents
      and humans, the innervation of CAT-producing, adrenomedullary chromaffin cells
      (AMCs) is immature or absent during early postnatal life, when these cells
      possess 'direct' hypoxia- and CO2/H(+)-chemosensing mechanisms. During asphyxial
      stressors at birth, these mechanisms contribute to a CAT surge that is critical
      for adaptation to extra-uterine life. These direct chemosensing mechanisms
      regress postnatally, in parallel with maturation of splanchnic innervation. Here,
      we review the evidence that neurotransmitters released from the splanchnic nerve
      during innervation activate signaling cascades that ultimately cause regression
      of direct AMC chemosensitivity to hypoxia and hypercapnia. In particular, we
      consider the roles of cholinergic and opioid receptor signaling, given that
      splanchnic nerves release acetylcholine and opiate peptides onto their respective
      postsynaptic nicotinic and opioid receptors on AMCs. Recent in vivo and in vitro
      studies in the rat suggest that interactions involving alpha7 nicotinic
      acetylcholine receptors (nAChRs), the hypoxia inducible factor (HIF)-2alpha
      signaling pathway, protein kinases and ATP-sensitive K(+) (KATP) channels
      contribute to the selective suppression of hypoxic chemosensitivity. In contrast,
      interactions involving MU- and/or delta-opiod receptor signaling pathways
      contribute to the suppression of both hypoxic and hypercapnic chemosensitivity,
      via regulation of the expression of KATP channels and carbonic anhydrase (CA I
      and II), respectively. These data suggest that the ontogeny of O2 and CO2/H(+)
      chemosensitivity in chromaffin cells can be regulated by the tonic release of
      presynaptic neurotransmitters. 

PMID- 24574384
TI  - Epigenetics as a source of variation in comparative animal physiology - or -
      Lamarck is lookin' pretty good these days.
AB  - Considerable variation is inherent both within and between comparative
      physiological data sets. Known sources for such variation include diet, gender,
      time of day and season of experiment, among many other factors, but a meta
      analysis of physiological studies shows that surprisingly few studies report
      controlling for these factors. In fact, less than 3% of comparative physiological
      papers mention epigenetics. However, our understanding of epigenetic influences
      on physiological processes is growing rapidly, and it is highly likely that
      epigenetic phenomena are an additional 'hidden' source of variation, particularly
      in wild-caught specimens. Recent studies have shown epigenetic inheritance of
      commonly studied traits such as metabolic rate (water fleas Daphnia magna; emu,
      Dromaius novaellandiae), hypoxic tolerance, cardiac performance (zebrafish, Danio
      rerio), as well as numerous morphological effects. The ecological and
      evolutionary significance of such epigenetic inheritance is discussed in a
      comparative physiological context. Finally, against this context of epigenetic
      inheritance of phenotype, this essay also provides a number of caveats and
      warnings regarding the interpretation of transgenerational phenotype modification
      as a true epigenetic phenomenon. Parental effects, sperm storage, multiple
      paternity and direct gamete exposure can all be confounding factors. Epigenetic
      inheritance may best be studied in animal models that can be maintained in the
      laboratory over multiple generations, to yield parental stock that themselves are
      free of epigenetic effects from the historical experiences of their parents. 

PMID- 24574382
TI  - Established and potential physiological roles of bicarbonate-sensing soluble
      adenylyl cyclase (sAC) in aquatic animals.
AB  - Soluble adenylyl cyclase (sAC) is a recently recognized source of the signaling
      molecule cyclic AMP (cAMP) that is genetically and biochemically distinct from
      the classic G-protein-regulated transmembrane adenylyl cyclases (tmACs).
      Mammalian sAC is distributed throughout the cytoplasm and it may be present in
      the nucleus and inside mitochondria. sAC activity is directly stimulated by HCO3(
      ), and sAC has been confirmed to be a HCO3(-) sensor in a variety of mammalian
      cell types. In addition, sAC can functionally associate with carbonic anhydrases
      to act as a de facto sensor of pH and CO2. The two catalytic domains of sAC are
      related to HCO3(-)-regulated adenylyl cyclases from cyanobacteria, suggesting the
      cAMP pathway is an evolutionarily conserved mechanism for sensing CO2 levels
      and/or acid/base conditions. Reports of sAC in aquatic animals are still limited
      but are rapidly accumulating. In shark gills, sAC senses blood alkalosis and
      triggers compensatory H(+) absorption. In the intestine of bony fishes, sAC
      modulates NaCl and water absorption. And in sea urchin sperm, sAC may participate
      in the initiation of flagellar movement and in the acrosome reaction.
      Bioinformatics and RT-PCR results reveal that sAC orthologs are present in most
      animal phyla. This review summarizes the current knowledge on the physiological
      roles of sAC in aquatic animals and suggests additional functions in which sAC
      may be involved. 

PMID- 24574385
TI  - The phylogeny and ontogeny of autonomic control of the heart and
      cardiorespiratory interactions in vertebrates.
AB  - Heart rate in vertebrates is controlled by activity in the autonomic nervous
      system. In spontaneously active or experimentally prepared animals, inhibitory
      parasympathetic control is predominant and is responsible for instantaneous
      changes in heart rate, such as occur at the first air breath following a period
      of apnoea in discontinuous breathers like inactive reptiles or species that
      surface to air breathe after a period of submersion. Parasympathetic control,
      exerted via fast-conducting, myelinated efferent fibres in the vagus nerve, is
      also responsible for beat-to-beat changes in heart rate such as the high
      frequency components observed in spectral analysis of heart rate variability.
      These include respiratory modulation of the heartbeat that can generate
      cardiorespiratory synchrony in fish and respiratory sinus arrhythmia in mammals.
      Both may increase the effectiveness of respiratory gas exchange. Although the
      central interactions generating respiratory modulation of the heartbeat seem to
      be highly conserved through vertebrate phylogeny, they are different in kind and
      location, and in most species are as yet little understood. The heart in
      vertebrate embryos possesses both muscarinic cholinergic and beta-adrenergic
      receptors very early in development. Adrenergic control by circulating
      catecholamines seems important throughout development. However, innervation of
      the cardiac receptors is delayed and first evidence of a functional cholinergic
      tonus on the heart, exerted via the vagus nerve, is often seen shortly before or
      immediately after hatching or birth, suggesting that it may be coordinated with
      the onset of central respiratory rhythmicity and subsequent breathing. 

PMID- 24574386
TI  - Aerobic scope fails to explain the detrimental effects on growth resulting from
      warming and elevated CO2 in Atlantic halibut.
AB  - As a consequence of increasing atmospheric CO2, the world's oceans are becoming
      warmer and more acidic. Whilst the ecological effects of these changes are poorly
      understood, it has been suggested that fish performance including growth will be
      reduced mainly as a result of limitations in oxygen transport capacity. Contrary
      to the predictions given by the oxygen- and capacity-limited thermal tolerance
      hypothesis, we show that aerobic scope and cardiac performance of Atlantic
      halibut (Hippoglossus hippoglossus) increase following 14-16 weeks exposure to
      elevated temperatures and even more so in combination with CO2-acidified
      seawater. However, the increase does not translate into improved growth,
      demonstrating that oxygen uptake is not the limiting factor for growth
      performance at high temperatures. Instead, long-term exposure to CO2-acidified
      seawater reduces growth at temperatures that are frequently encountered by this
      species in nature, indicating that elevated atmospheric CO2 levels may have
      serious implications on fish populations in the future. 

PMID- 24574387
TI  - Amphibious hearing in spotted seals (Phoca largha): underwater audiograms, aerial
      audiograms and critical ratio measurements.
AB  - Spotted seals (Phoca largha) inhabit Arctic regions that are facing both rapid
      climate change and increasing industrialization. While little is known about
      their sensory capabilities, available knowledge suggests that spotted seals and
      other ice seals use sound to obtain information from the surrounding environment.
      To quantitatively assess their auditory capabilities, the hearing of two young
      spotted seals was tested using a psychophysical paradigm. Absolute detection
      thresholds for tonal sounds were measured in air and under water over the
      frequency range of hearing, and critical ratios were determined using octave-band
      masking noise in both media. The behavioral audiograms show a range of best
      sensitivity spanning four octaves in air, from approximately 0.6 to 11 kHz. The
      range of sensitive hearing extends across seven octaves in water, with lowest
      thresholds between 0.3 and 56 kHz. Critical ratio measurements were similar in
      air and water and increased monotonically from 12 dB at 0.1 kHz to 30 dB at 25.6
      kHz, indicating that the auditory systems of these seals are quite efficient at
      extracting signals from background noise. This study demonstrates that spotted
      seals possess sound reception capabilities different from those previously
      described for ice seals, and more similar to those reported for harbor seals
      (Phoca vitulina). The results are consistent with the amphibious lifestyle of
      these seals and their apparent reliance on sound. The hearing data reported
      herein are the first available for spotted seals and can inform best management
      practices for this vulnerable species in a changing Arctic. 

PMID- 24574388
TI  - Larval vision contributes to gregarious settlement in barnacles: adult red
      fluorescence as a possible visual signal.
AB  - Gregarious settlement, an essential behavior for many barnacle species that can
      only reproduce by mating with a nearby barnacle, has long been thought to rely on
      larval ability to recognize chemical signals from conspecifics during settlement.
      However, the cyprid, the settlement stage larva in barnacles, has one pair of
      compound eyes that appear only at the late nauplius VI and cyprid stages, but the
      function(s) of these eyes remains unknown. Here we show that cyprids of the
      intertidal barnacle Balanus (=Amphibalanus) amphitrite can locate adult barnacles
      even in the absence of chemical cues, and prefer to settle around them probably
      via larval sense of vision. We also show that the cyprids can discriminate color
      and preferred to settle on red surfaces. Moreover, we found that shells of adult
      B. amphitrite emit red auto-fluorescence and the adult extracts with the
      fluorescence as a visual signal attracted cyprid larvae to settle around it. We
      propose that the perception of specific visual signals can be involved in
      behavior of zooplankton including marine invertebrate larvae, and that barnacle
      auto-fluorescence may be a specific signal involved in gregarious larval
      settlement. 

PMID- 24574389
TI  - An experimental and morphometric test of the relationship between vertebral
      morphology and joint stiffness in Nile crocodiles (Crocodylus niloticus).
AB  - Despite their semi-aquatic mode of life, modern crocodylians use a wide range of
      terrestrial locomotor behaviours, including asymmetrical gaits otherwise only
      found in mammals. The key to these diverse abilities may lie in the axial
      skeleton. Correlations between vertebral morphology and both intervertebral joint
      stiffness and locomotor behaviour have been found in other animals, but the
      vertebral mechanics of crocodylians have not yet been experimentally and
      quantitatively tested. We measured the passive mechanics and morphology of the
      thoracolumbar vertebral column in Crocodylus niloticus in order to validate a
      method to infer intervertebral joint stiffness based on morphology. Passive
      stiffness of eight thoracic and lumbar joints was tested in dorsal extension,
      ventral flexion and mediolateral flexion using cadaveric specimens. Fifteen
      measurements that we deemed to be potential correlates of stiffness were taken
      from each vertebra and statistically tested for correlation with joint stiffness.
      We found that the vertebral column of C. niloticus is stiffer in dorsoventral
      flexion than in lateral flexion and, in contrast to that of many mammals, shows
      an increase in joint stiffness in the lumbar region. Our findings suggest that
      the role of the axial column in crocodylian locomotion may be functionally
      different from that in mammals, even during analogous gaits. A moderate
      proportion of variation in joint stiffness (R(2)=0.279-0.520) was predicted by
      centrum width and height, neural spine angle and lamina width. These results
      support the possible utility of some vertebral morphometrics in predicting
      mechanical properties of the vertebral column in crocodiles, which also should be
      useful for forming functional hypotheses of axial motion during locomotion in
      extinct archosaurs. 

PMID- 24574391
TI  - Heat shock protein 70 enhances mucosal immunity against human norovirus when
      coexpressed from a vesicular stomatitis virus vector.
AB  - Human norovirus (NoV) accounts for 95% of nonbacterial gastroenteritis worldwide.
      Currently, there is no vaccine available to combat human NoV as it is not
      cultivable and lacks a small-animal model. Recently, we demonstrated that
      recombinant vesicular stomatitis virus (rVSV) expressing human NoV capsid protein
      (rVSV-VP1) induced strong immunities in mice (Y. Ma and J. Li, J. Virol. 85:2942
      2952, 2011). To further improve the safety and efficacy of the vaccine candidate,
      heat shock protein 70 (HSP70) was inserted into the rVSV-VP1 backbone vector. A
      second construct was generated in which the firefly luciferase (Luc) gene was
      inserted in place of HSP70 as a control for the double insertion. The resultant
      recombinant viruses (rVSV-HSP70-VP1 and rVSV-Luc-VP1) were significantly more
      attenuated in cell culture and viral spread in mice than rVSV-VP1. At the
      inoculation dose of 1.0 * 10(6) PFU, rVSV-HSP70-VP1 triggered significantly
      higher vaginal IgA than rVSV-VP1 and significantly higher fecal and vaginal IgA
      responses than rVSV-Luc-VP1, although serum IgG and T cell responses were
      similar. At the inoculation dose of 5.0 * 10(6) PFU, rVSV-HSP70-VP1 stimulated
      significantly higher T cell, fecal, and vaginal IgA responses than rVSV-VP1.
      Fecal and vaginal IgA responses were also significantly increased when combined
      vaccination of rVSV-VP1 and rVSV-HSP70 was used. Collectively, these data
      indicate that (i) insertion of an additional gene (HSP70 or Luc) into the rVSV
      VP1 backbone further attenuates the VSV-based vaccine in vitro and in vivo, thus
      improving the safety of the vaccine candidate, and (ii) HSP70 enhances the human
      NoV-specific mucosal and T cell immunities triggered by a VSV-based human NoV
      vaccine. IMPORTANCE: Human norovirus (NoV) is responsible for more than 95% of
      acute nonbacterial gastroenteritis worldwide. Currently, there is no vaccine for
      this virus. Development of a live attenuated vaccine for human NoV has not been
      possible because it is uncultivable. Thus, a live vector-based vaccine may
      provide an alternative vaccine strategy. In this study, we developed a vesicular
      stomatitis virus (VSV)-based human NoV vaccine candidate. We constructed rVSV
      HSP70-VP1, coexpressing heat shock protein (HSP70) and capsid (VP1) genes of
      human NoV, and rVSV-Luc-VP1, coexpressing firefly luciferase (Luc) and VP1 genes.
      We found that VSVs with a double gene insertion were significantly more
      attenuated than VSV with a single VP1 insertion (rVSV-VP1). Furthermore, we found
      that coexpression or coadministration of HSP70 from VSV vector significantly
      enhanced human NoV-specific mucosal immunity. Collectively, we developed an
      improved live vectored vaccine candidate for human NoV which will be useful for
      future clinical studies.

PMID- 24574392
TI  - Varicella-zoster virus and herpes simplex virus 1 can infect and replicate in the
      same neurons whether co- or superinfected.
AB  - The two human neurotropic alphaherpesviruses varicella-zoster virus (VZV) and
      herpes simplex virus type 1 (HSV1) both establish latency in sensory ganglia.
      Human trigeminal ganglia are known to frequently harbor both viruses, and there
      is evidence to suggest the presence of both VZV and HSV1 DNA in the same neuron.
      We ask here whether VZV and HSV1 can exclude themselves and each other and
      whether they can productively infect the same cells in human neurons and human
      foreskin fibroblasts (HFF). Simultaneous infection (coinfection) or consecutive
      infection (superinfection) was assessed using cell-free HSV1 and VZV expressing
      fluorescent reporter proteins. Automated analysis was carried out to detect
      singly and dually infected cells. We demonstrate that VZV and HSV1 both display
      efficient superinfection exclusion (SE) in HFF, with each virus excluding either
      itself or the other virus. While SE also occurred in neurons, it was with much
      lower efficiency. Both alphaherpesviruses productively infected the same neurons,
      whether applied simultaneously or even consecutively, albeit at lower
      frequencies. IMPORTANCE: Superinfection exclusion by VZV for itself or the
      related neurotropic alphaherpesvirus HSV1 has been studied here for the first
      time. We find that while these viruses display classic SE in fibroblasts, SE is
      less efficient for both HSV1 and VZV in human neurons. The ability of multiple
      VZV strains to productively infect the same neurons has important implications in
      terms of recombination of both wild-type and vaccine strains in patients.

PMID- 24574390
TI  - Dendritic cell-lymphocyte cross talk downregulates host restriction factor SAMHD1
      and stimulates HIV-1 replication in dendritic cells.
AB  - Human immunodeficiency virus type 1 (HIV-1) replication in dendritic cells (DCs)
      is restricted by SAMHD1. This factor is counteracted by the viral protein Vpx;
      Vpx is found in HIV-2 and simian immunodeficiency virus (SIV) from sooty
      mangabeys (SIVsm) or from macaques (SIVmac) but is absent from HIV-1. We
      previously observed that HIV-1 replication in immature DCs is stimulated by
      cocultivation with primary T and B lymphocytes, suggesting that HIV-1 restriction
      in DCs may be overcome under coculture conditions. Here, we aimed to decipher the
      mechanism of SAMHD1-mediated restriction in DC-lymphocyte coculture. We found
      that coculture with lymphocytes downregulated SAMHD1 expression and was
      associated with increased HIV-1 replication in DCs. Moreover, in infected DC-T
      lymphocyte cocultures, DCs acquired maturation status and secreted type 1
      interferon (alpha interferon [IFN-alpha]). The blockade of DC-lymphocyte cross
      talk by anti-ICAM-1 antibody markedly inhibited the stimulation of HIV-1
      replication and prevented the downregulation of SAMHD1 expression in cocultured
      DCs. These results demonstrate that, in contrast to purified DCs, cross talk with
      lymphocytes downregulates SAMHD1 expression in DCs, triggering HIV-1 replication
      and an antiviral immune response. Therefore, HIV-1 replication and immune sensing
      by DCs should be investigated in more physiologically relevant models of
      DC/lymphocyte coculture. IMPORTANCE: SAMHD1 restricts HIV-1 replication in
      dendritic cells (DCs). Here, we demonstrate that, in a coculture model of DCs and
      lymphocytes mimicking early mucosal HIV-1 infection, stimulation of HIV-1
      replication in DCs is associated with downregulation of SAMHD1 expression and
      activation of innate immune sensing by DCs. We propose that DC-lymphocyte cross
      talk occurring in vivo modulates host restriction factor SAMHD1, promoting HIV-1
      replication in cellular reservoirs and stimulating immune sensing.

PMID- 24574393
TI  - Mitophagy enhances oncolytic measles virus replication by mitigating DDX58/RIG-I
      like receptor signaling.
AB  - The success of future clinical trials with oncolytic viruses depends on the
      identification and the control of mechanisms that modulate their therapeutic
      efficacy. In particular, little is known about the role of autophagy in infection
      by attenuated measles virus of the Edmonston strain (MV-Edm). We investigated the
      interaction between autophagy, innate immune response, and oncolytic activity of
      MV-Edm, since the antiviral immune response is a known factor limiting
      virotherapies. We report that MV-Edm exploits selective autophagy to mitigate the
      innate immune response mediated by DDX58/RIG-I like receptors (RLRs) in non-small
      cell lung cancer (NSCLC) cells. Both RNA interference (RNAi) and overexpression
      approaches demonstrate that autophagy enhances viral replication and inhibits the
      production of type I interferons regulated by RLRs. We show that MV-Edm
      unexpectedly triggers SQSTM1/p62-mediated mitophagy, resulting in decreased
      mitochondrion-tethered mitochondrial antiviral signaling protein (MAVS) and
      subsequently weakening the innate immune response. These results unveil a novel
      infectious strategy based on the usurpation of mitophagy leading to mitigation of
      the innate immune response. This finding provides a rationale to modulate
      autophagy in oncolytic virotherapy. IMPORTANCE: In vitro studies, preclinical
      experiments in vivo, and clinical trials with humans all indicate that oncolytic
      viruses hold promise for cancer therapy. Measles virus of the Edmonston strain
      (MV-Edm), which is an attenuated virus derived from the common wild-type measles
      virus, is paradigmatic for therapeutic oncolytic viruses. MV-Edm replicates
      preferentially in and kills cancer cells. The efficiency of MV-Edm is limited by
      the immune response of the host against viruses. In our study, we revealed that
      MV-Edm usurps a homeostatic mechanism of intracellular degradation of
      mitochondria, coined mitophagy, to attenuate the innate immune response in cancer
      cells. This strategy might provide a replicative advantage for the virus against
      the development of antiviral immune responses by the host. These findings are
      important since they may not only indicate that inducers of autophagy could
      enhance the efficacy of oncolytic therapies but also provide clues for antiviral
      therapy by targeting SQSTM1/p62-mediated mitophagy.

PMID- 24574394
TI  - In vivo ablation of type I interferon receptor from cardiomyocytes delays
      coxsackieviral clearance and accelerates myocardial disease.
AB  - Acute coxsackievirus B3 (CVB3) infection is one of the most prevalent causes of
      acute myocarditis, a disease that frequently is identified only after the sudden
      death of apparently healthy individuals. CVB3 infects cardiomyocytes, but the
      infection is highly focal, even in the absence of a strong adaptive immune
      response, suggesting that virus spread within the heart may be tightly
      constrained by the innate immune system. Type I interferons (T1IFNs) are an
      obvious candidate, and T1IFN receptor (T1IFNR) knockout mice are highly
      susceptible to CVB3 infection, succumbing within a few days of challenge. Here,
      we investigated the role of T1IFNs in the heart using a mouse model in which the
      T1IFNR gene can be ablated in vivo, specifically in cardiomyocytes. We found that
      T1IFN signaling into cardiomyocytes contributed substantially to the suppression
      of viral replication and infectious virus yield in the heart; in the absence of
      such signaling, virus titers were markedly elevated by day 3 postinfection (p.i.)
      and remained high at day 12 p.i., a time point at which virus was absent from
      genetically intact littermates, suggesting that the T1IFN-unresponsive
      cardiomyocytes may act as a safe haven for the virus. Nevertheless, in these mice
      the myocardial infection remained highly focal, despite the cardiomyocytes'
      inability to respond to T1IFN, indicating that other factors, as yet
      unidentified, are sufficient to prevent the more widespread dissemination of the
      infection throughout the heart. The absence of T1IFN signaling into
      cardiomyocytes also was accompanied by a profound acceleration and exacerbation
      of myocarditis and by a significant increase in mortality. IMPORTANCE: Acute
      coxsackievirus B3 (CVB3) infection is one of the most common causes of acute
      myocarditis, a serious and sometimes fatal disease. To optimize treatment, it is
      vital that we identify the immune factors that limit virus spread in the heart
      and other organs. Type I interferons play a key role in controlling many virus
      infections, but it has been suggested that they may not directly impact CVB3
      infection within the heart. Here, using a novel line of transgenic mice, we show
      that these cytokines signal directly into cardiomyocytes, limiting viral
      replication, myocarditis, and death.

PMID- 24574396
TI  - Development of an adenovirus-based respiratory syncytial virus vaccine:
      preclinical evaluation of efficacy, immunogenicity, and enhanced disease in a
      cotton rat model.
AB  - The lack of a vaccine against respiratory syncytial virus (RSV) is a challenging
      and serious gap in preventive medicine. Herein, we characterize the
      immunogenicity of an adenovirus serotype 5-based RSV vaccine encoding the fusion
      (F) protein (Ad5.RSV-F) and the protection provided following immunization with
      Ad5.RSV-F and assess its potential for producing enhanced disease in a cotton rat
      (CR) model. Animals were immunized intranasally (i.n.) and/or intramuscularly
      (i.m.) and subsequently challenged with RSV/A/Tracy (i.n.) to assess protection.
      Robust immune responses were seen in CRs vaccinated with Ad5.RSV-F given i.m. or
      i.n., and these responses correlated with reduced replication of the virus in
      noses and lungs after challenge. Neutralizing antibody responses following
      immunization with a single dose of Ad5.RSV-F at 1 * 10(11) viral particles (v.p.)
      elicited antibody titers 64- to 256-fold greater than those seen after natural
      infection. CRs boosted with Ad5.RSV-F i.n. 28 days after an i.m. dose also had
      significant increases in neutralizing antibody titers. Antibody affinity for
      different F-protein antigenic sites revealed substantial differences between
      antibodies elicited by Ad5.RSV-F and those seen after RSV infection; differences
      in antibody profiles were also seen between CRs given Ad5.RSV-F i.m. and CRs
      given Ad5.RSV-F i.n. Ad5.RSV-F priming did not result in enhanced disease
      following live-virus challenge, in contrast to the histopathology seen in CRs
      given the formalin-inactivated RSV/A/Burnett vaccine. IMPORTANCE: Respiratory
      syncytial virus (RSV) is the most common cause of acute lower respiratory
      infection in infants and young children and a serious health threat in the
      immunocompromised and the elderly. Infection severity increased in children in an
      immunization trial, hampering the over 4-decade-long quest for a successful RSV
      vaccine. In this study, we show that a genetically engineered RSV-F-encoding
      adenoviral vector provides protective immunity against RSV challenge without
      enhanced lung disease in cotton rats (CRs). CRs were vaccinated under a number of
      different regimens, and the immunity induced by the recombinant adenoviral RSV
      vaccine administered by use of an intramuscular prime-intranasal boost regimen
      may provide the best protection for young infants and children at risk of RSV
      infection, since this population is naive to adenoviral preformed immunity.
      Overall, this report describes a potential RSV vaccine candidate that merits
      further evaluation in a phase I clinical study in humans.

PMID- 24574397
TI  - Activities of transmitted/founder and chronic clade B HIV-1 Vpu and a C-terminal
      polymorphism specifically affecting virion release.
AB  - Acute HIV-1 infection is characterized by a type I interferon response, resulting
      in the induction of host restriction factors. HIV-1 has evolved to counteract
      these factors, and one such adaptation, the ability of Vpu to counteract
      BST2/tetherin, is associated with the evolution of simian immunodeficiency virus
      (SIVcpz) into pandemic group M human immunodeficiency virus type 1 (HIV-1).
      During transmission between individuals, very few viruses or even a single virus,
      the "transmitted/founder" (T/F) virus, gives rise to the new infection, but in
      the new host the selective pressure of the immune response yields the diverse
      "quasispecies" of chronic infection. Here we examine the functional
      characteristics of Vpu proteins encoded by T/F viruses compared to acute and
      chronic viruses from longitudinally sampled subjects. The studied T/F Vpu
      proteins showed a trend toward optimized CD4 downregulation compared to chronic
      Vpu proteins but did not differ substantially in their ability to downregulate
      BST2 or enhance virion release, although individual clones from each group were
      impaired in these activities. Analysis of the functionally impaired clones
      identified a C-terminal residue, W76, as important specifically for Vpu
      enhancement of virion release. Primary Vpu clones encoding a W76G polymorphism,
      or site-directed mutants encoding a W76G substitution, were impaired in their
      ability to enhance virion release, but they were not defective for BST2 surface
      downregulation. Conversely, the virion release function of impaired primary
      clones was restored by creating a G76W substitution. The identification of W76 as
      important for virion release enhancement that is independent of BST2 surface
      downregulation supports the potential to mechanistically separate these functions
      of Vpu. IMPORTANCE: To establish infection in a host, HIV-1 must evade the host's
      immune response, including the production of antiviral factors. HIV-1 encodes
      proteins that antagonize these defenses, including Vpu. Vpu counteracts the host
      protein BST2, which blocks the release of progeny viruses from the host cell. To
      determine the importance of Vpu activity to HIV-1 transmission, this study
      assessed the functionality of Vpu from viruses isolated soon after transmission
      ("transmitted/founder" viruses) compared to isolates from chronic infection.
      Although the anti-BST2 activity of Vpu proteins from the tested
      transmitted/founder viruses did not differ from the activity of the chronic Vpu
      proteins, the transmitted/founder Vpu proteins trended toward having superior
      activity against another host protein, CD4. Further, this study identified an
      amino acid near the C terminus of Vpu that is specifically important for Vpu's
      ability to enhance the release of progeny virus from the host cell, supporting
      the notion of a new mechanism for this function of Vpu.

PMID- 24574395
TI  - An unbiased genetic screen reveals the polygenic nature of the influenza virus
      anti-interferon response.
AB  - Influenza A viruses counteract the cellular innate immune response at several
      steps, including blocking RIG I-dependent activation of interferon (IFN)
      transcription, interferon (IFN)-dependent upregulation of IFN-stimulated genes
      (ISGs), and the activity of various ISG products; the multifunctional NS1 protein
      is responsible for most of these activities. To determine the importance of other
      viral genes in the interplay between the virus and the host IFN response, we
      characterized populations and selected mutants of wild-type viruses selected by
      passage through non-IFN-responsive cells. We reasoned that, by allowing
      replication to occur in the absence of the selection pressure exerted by IFN, the
      virus could mutate at positions that would normally be restricted and could thus
      find new optimal sequence solutions. Deep sequencing of selected virus
      populations and individual virus mutants indicated that nonsynonymous mutations
      occurred at many phylogenetically conserved positions in nearly all virus genes.
      Most individual mutants selected for further characterization induced IFN and
      ISGs and were unable to counteract the effects of exogenous IFN, yet only one
      contained a mutation in NS1. The relevance of these mutations for the virus
      phenotype was verified by reverse genetics. Of note, several virus mutants
      expressing intact NS1 proteins exhibited alterations in the M1/M2 proteins and
      accumulated large amounts of deleted genomic RNAs but nonetheless replicated to
      high titers. This suggests that the overproduction of IFN inducers by these
      viruses can override NS1-mediated IFN modulation. Altogether, the results suggest
      that influenza viruses replicating in IFN-competent cells have tuned their
      complete genomes to evade the cellular innate immune system and that serial
      replication in non-IFN-responsive cells allows the virus to relax from these
      constraints and find a new genome consensus within its sequence space.
      IMPORTANCE: In natural virus infections, the production of interferons leads to
      an antiviral state in cells that effectively limits virus replication. The
      interferon response places considerable selection pressure on viruses, and they
      have evolved a variety of ways to evade it. Although the influenza virus NS1
      protein is a powerful interferon antagonist, the contributions of other viral
      genes to interferon evasion have not been well characterized. Here, we examined
      the effects of alleviating the selection pressure exerted by interferon by
      serially passaging influenza viruses in cells unable to respond to interferon.
      Viruses that grew to high titers had mutations at many normally conserved
      positions in nearly all genes and were not restricted to the NS1 gene. Our
      results demonstrate that influenza viruses have fine-tuned their entire genomes
      to evade the interferon response, and by removing interferon-mediated
      constraints, viruses can mutate at genome positions normally restricted by the
      interferon response.

PMID- 24574399
TI  - Mouse dipeptidyl peptidase 4 is not a functional receptor for Middle East
      respiratory syndrome coronavirus infection.
AB  - Human dipeptidyl peptidase 4 (hDPP4) was recently identified as the receptor for
      Middle East respiratory syndrome coronavirus (MERS-CoV) infection, suggesting
      that other mammalian DPP4 orthologs may also support infection. We demonstrate
      that mouse DPP4 cannot support MERS-CoV infection. However, employing mouse DPP4
      as a scaffold, we identified two critical amino acids (A288L and T330R) that
      regulate species specificity in the mouse. This knowledge can support the
      rational design of a mouse-adapted MERS-CoV for rapid assessment of therapeutics.

PMID- 24574400
TI  - Crystal structure of Marburg virus VP24.
AB  - The VP24 protein plays an essential, albeit poorly understood role in the
      filovirus life cycle. VP24 is only 30% identical between Marburg virus and the
      ebolaviruses. Furthermore, VP24 from the ebolaviruses is immunosuppressive, while
      that of Marburg virus is not. The crystal structure of Marburg virus VP24,
      presented here, reveals that although the core is similar between the viral
      genera, Marburg VP24 is distinguished by a projecting beta-shelf and an alternate
      conformation of the N-terminal polypeptide. 

PMID- 24574398
TI  - Complementary induction of immunogenic cell death by oncolytic parvovirus H-1PV
      and gemcitabine in pancreatic cancer.
AB  - Novel therapies employing oncolytic viruses have emerged as promising anticancer
      modalities. The cure of particularly aggressive malignancies requires induction
      of immunogenic cell death (ICD), coupling oncolysis with immune responses via
      calreticulin, ATP, and high-mobility group box protein B1 (HMGB1) release from
      dying tumor cells. The present study shows that in human pancreatic cancer cells
      (pancreatic ductal adenocarcinoma [PDAC] cells n=4), oncolytic parvovirus H-1 (H
      1PV) activated multiple interconnected death pathways but failed to induce
      calreticulin exposure or ATP release. In contrast, H-1PV elevated extracellular
      HMGB1 levels by 4.0+/-0.5 times (58%+/-9% of total content; up to 100 ng/ml) in
      all infected cultures, whether nondying, necrotic, or apoptotic. An alternative
      secretory route allowed H-1PV to overcome the failure of gemcitabine to trigger
      HMGB1 release, without impeding cytotoxicity or other ICD activities of the
      standard PDAC medication. Such broad resistance of H-1PV-induced HMGB1 release to
      apoptotic blockage coincided with but was uncoupled from an autocrine interleukin
      1beta (IL-1beta) loop. That and the pattern of viral determinants maintained in
      gemcitabine-treated cells suggested the activation of an inflammasome/caspase 1
      (CASP1) platform alongside DNA detachment and/or nuclear exclusion of HMGB1
      during early stages of the viral life cycle. We concluded that H-1PV infection of
      PDAC cells is signaled through secretion of the alarmin HMGB1 and, besides its
      own oncolytic effect, might convert drug-induced apoptosis into an ICD process. A
      transient arrest of cells in the cyclin A1-rich S phase would suffice to support
      compatibility of proliferation-dependent H-1PV with cytotoxic regimens. These
      properties warrant incorporation of the oncolytic virus H-1PV, which is not
      pathogenic in humans, into multimodal anticancer treatments. IMPORTANCE: The
      current therapeutic concepts targeting aggressive malignancies require an
      induction of immunogenic cell death characterized by exposure of calreticulin
      (CRT) as well as release of ATP and HMGB1 from dying cells. In pancreatic tumor
      cells (PDAC cells) infected with the oncolytic parvovirus H-1PV, only HMGB1 was
      released by all infected cells, whether nondying, necrotic, or succumbing to one
      of the programmed death pathways, including contraproductive apoptosis. Our data
      suggest that active secretion of HMGB1 from PDAC cells is a sentinel reaction
      emerging during early stages of the viral life cycle, irrespective of cell death,
      that is compatible with and complements cytotoxic regimens. Consistent induction
      of HMGB1 secretion raised the possibility that this reaction might be a general
      "alarming" phenomenon characteristic of H-1PV's interaction with the host cell;
      release of IL-1beta points to the possible involvement of a danger-sensing
      inflammasome platform. Both provide a basis for further virus-oriented studies.

PMID- 24574402
TI  - A critical determinant of neurological disease associated with highly pathogenic
      tick-borne flavivirus in mice.
AB  - Tick-borne encephalitis virus (TBEV) and Omsk hemorrhagic fever virus (OHFV) are
      highly pathogenic tick-borne flaviviruses; TBEV causes neurological disease in
      humans, while OHFV causes a disease typically identified with hemorrhagic fever.
      Although TBEV and OHFV are closely related genetically, the viral determinants
      responsible for these distinct disease phenotypes have not been identified. In
      this study, chimeric viruses incorporating components of TBEV and OHFV were
      generated using infectious clone technology, and their pathological
      characteristics were analyzed in a mouse model to identify virus-specific
      determinants of disease. We found that only four amino acids near the C terminus
      of the NS5 protein were primarily responsible for the development of neurological
      disease. Mutation of these four amino acids had no effect on viral replication or
      histopathological features, including inflammatory responses, in mice. These
      findings suggest a critical role for NS5 in stimulating neuronal dysfunction and
      degeneration following TBEV infection and provide new insights into the molecular
      mechanisms underlying the pathogenesis of tick-borne flaviviruses. IMPORTANCE:
      Tick-borne encephalitis virus (TBEV) and Omsk hemorrhagic fever virus (OHFV)
      belong to the tick-borne encephalitis serocomplex, genus Flavivirus, family
      Flaviviridae. Although TBEV causes neurological disease in humans while OHFV
      causes a disease typically identified with hemorrhagic fever. In this study, we
      investigated the viral determinants responsible for the different disease
      phenotypes using reverse genetics technology. We identified a cluster of only
      four amino acids in nonstructural protein 5 primarily involved in the development
      of neurological disease in a mouse model. Moreover, the effect of these four
      amino acids was independent of viral replication property and did not affect the
      formation of virus-induced lesions in the brain directly. These data suggest that
      these amino acids may be involved in the induction of neuronal dysfunction and
      degeneration in virus-infected neurons, ultimately leading to the neurological
      disease phenotype. These findings provide new insight into the molecular
      mechanisms of tick-borne flavivirus pathogenesis.

PMID- 24574401
TI  - Coxsackievirus A9 infects cells via nonacidic multivesicular bodies.
AB  - Coxsackievirus A9 (CVA9) is a member of the human enterovirus B species in the
      Enterovirus genus of the family Picornaviridae. According to earlier studies,
      CVA9 binds to alphaVbeta3 and alphaVbeta6 integrins on the cell surface and
      utilizes beta2-microglobulin, dynamin, and Arf6 for internalization. However, the
      structures utilized by the virus for internalization and uncoating are less well
      understood. We show here, based on electron microscopy, that CVA9 is found in
      multivesicular structures 2 h postinfection (p.i.). A neutral red labeling assay
      revealed that uncoating occurs mainly around 2 h p.i., while double-stranded RNA
      is found in the cytoplasm after 3 h p.i. The biogenesis of multivesicular bodies
      (MVBs) is crucial for promoting infection, as judged by the strong inhibitory
      effect of the wild-type form of Hrs and dominant negative form of VPS4 in CVA9
      infection. CVA9 infection is dependent on phospholipase C at the start of
      infection, whereas Rac1 is especially important between 1 and 3 h p.i., when the
      virus is in endosomes. Several lines of evidence implicate that low pH does not
      play a role in CVA9 infection. The infection is not affected by Bafilomycin A1.
      In addition, CVA9 is not targeted to acidic late endosomes or lysosomes, and the
      MVBs accumulating CVA9 have a neutral pH. Thus, CVA9 is the second enterovirus
      demonstrated so far, after echovirus 1, that can trigger neutral MVBs, which are
      important for virus infection. IMPORTANCE: We demonstrate here that the
      enterovirus coxsackievirus A9 (CVA9) uses a nonclathrin and nonacidic pathway to
      infect cells. CVA9 does not accumulate in conventional late endosomes or
      lysosomes. We found that inhibitors of phospholipase C (PLC), Rac1, and the
      Na(+)/H(+) exchanger decreased CVA9 infection. The PLC inhibitor acts on early
      entry, the Rac1 inhibitor acts between 1 and 3 h, when the virus is in endosomes,
      and the Na(+)/H(+) exchange inhibitor acts during various steps during the virus
      life cycle. The infection depends on the formation of novel neutral
      multivesicular bodies (MVBs), which accumulate CVA9 during the first hours of
      entry. Thus, CVA9 is the second enterovirus demonstrated so far, after echovirus
      1, that can trigger formation of neutral MVBs. The data show that these
      enteroviruses favor nonacidic conditions and complex MVBs to promote virus
      infection.

PMID- 24574403
TI  - Yeast virus-derived stimulator of the innate immune system augments the efficacy
      of virus vector-based immunotherapy.
AB  - To identify novel stimulators of the innate immune system, we constructed a panel
      of eight HEK293 cell lines double positive for human Toll-like receptors (TLRs)
      and an NF-kappaB-inducible reporter gene. Screening of a large variety of
      compounds and cellular extracts detected a TLR3-activating compound in a
      microsomal yeast extract. Fractionation of this extract identified an RNA
      molecule of 4.6 kb, named nucleic acid band 2 (NAB2), that was sufficient to
      confer the activation of TLR3. Digests with single- and double-strand-specific
      RNases showed the double-strand nature of this RNA, and its sequence was found to
      be identical to that of the genome of the double-stranded RNA (dsRNA) L-BC virus
      of Saccharomyces cerevisiae. A large-scale process of production and purification
      of this RNA was established on the basis of chemical cell lysis and dsRNA
      specific chromatography. NAB2 complexed with the cationic lipid Lipofectin but
      neither NAB2 nor Lipofectin alone induced the secretion of interleukin-12(p70)
      [IL-12(p70)], alpha interferon, gamma interferon-induced protein 10, macrophage
      inflammatory protein 1beta, or IL-6 in human monocyte-derived dendritic cells.
      While NAB2 activated TLR3, Lipofectin-stabilized NAB2 also signaled via the
      cytoplasmic sensor for RNA recognition MDA-5. A significant increase of RMA-MUC1
      tumor rejection and survival was observed in C57BL/6 mice after prophylactic
      vaccination with MUC1-encoding modified vaccinia virus Ankara (MVA) and NAB2
      Lipofectin. This combination of immunotherapies strongly increased at the
      injection sites the percentage of infiltrating natural killer (NK) cells and
      plasmacytoid dendritic cells (pDCs), cell types which can modulate innate and
      adaptive immune responses. IMPORTANCE: Virus-based cancer vaccines offer a good
      alternative to the treatment of cancer but could be improved. Starting from a
      screening approach, we have identified and characterized an unexplored biological
      molecule with immunomodulatory characteristics which augments the efficacy of an
      MVA-based immunotherapeutic agent. The immune modulator consists of the purified
      dsRNA genome isolated from a commercially used yeast strain, NAB2, mixed with a
      cationic lipid, Lipofectin. NAB2-Lipofectin stimulates the immune system via TLR3
      and MDA-5. When it was injected at the MVA vaccination site, the immune modulator
      increased survival in a preclinical tumor model. We could demonstrate that NAB2
      Lipofectin augments the MVA-induced infiltration of natural killer and
      plasmacytoid dendritic cells. We suggest indirect mechanisms of activation of
      these cell types by the influence of NAB2-Lipofectin on innate and adaptive
      immunity. Detailed analysis of cell migration at the vaccine injection site and
      the appropriate choice of an immune modulator should be considered to achieve the
      rational improvement of virus vector-based vaccination by immune modulators.

PMID- 24574404
TI  - Defective interfering influenza virus RNAs: time to reevaluate their clinical
      potential as broad-spectrum antivirals?
AB  - Defective interfering (DI) RNAs are highly deleted forms of the infectious genome
      that are made by most families of RNA viruses. DI RNAs retain replication and
      packaging signals, are synthesized preferentially over infectious genomes, and
      are packaged as DI virus particles which can be transmitted to susceptible cells.
      Their ability to interfere with the replication of infectious virus in cell
      culture and their potential as antivirals in the clinic have long been known.
      However, until now, no realistic formulation has been described. In this review,
      we consider the early evidence of antiviral activity by DI viruses and, using the
      example of DI influenza A virus, outline developments that have led to the
      production of a cloned DI RNA that is highly active in preclinical studies not
      only against different subtypes of influenza A virus but also against
      heterologous respiratory viruses. These data suggest the timeliness of
      reassessing the potential of DI viruses as a novel class of antivirals that may
      have general applicability. 

PMID- 24574405
TI  - Human herpesvirus 6A infection in CD46 transgenic mice: viral persistence in the
      brain and increased production of proinflammatory chemokines via Toll-like
      receptor 9.
AB  - Human herpesvirus 6 (HHV-6) is widely spread in the human population and has been
      associated with several neuroinflammatory diseases, including multiple sclerosis.
      To develop a small-animal model of HHV-6 infection, we analyzed the
      susceptibility of several lines of transgenic mice expressing human CD46,
      identified as a receptor for HHV-6. We showed that HHV-6A (GS) infection results
      in the expression of viral transcripts in primary brain glial cultures from CD46
      expressing mice, while HHV-6B (Z29) infection was inefficient. HHV-6A DNA
      persisted for up to 9 months in the brain of CD46-expressing mice but not in the
      nontransgenic littermates, whereas HHV-6B DNA levels decreased rapidly after
      infection in all mice. Persistence in the brain was observed with infectious but
      not heat-inactivated HHV-6A. Immunohistological studies revealed the presence of
      infiltrating lymphocytes in periventricular areas of the brain of HHV-6A-infected
      mice. Furthermore, HHV-6A stimulated the production of a panel of proinflammatory
      chemokines in primary brain glial cultures, including CCL2, CCL5, and CXCL10, and
      induced the expression of CCL5 in the brains of HHV-6A-infected mice. HHV-6A
      induced production of chemokines in the primary glial cultures was dependent on
      the stimulation of toll-like receptor 9 (TLR9). Finally, HHV-6A induced signaling
      through human TLR9 as well, extending observations from the murine model to human
      infection. Altogether, this study presents a first murine model for HHV-6A
      induced brain infection and suggests a role for TLR9 in the HHV-6A-initiated
      production of proinflammatory chemokines in the brain, opening novel perspectives
      for the study of virus-associated neuropathology. IMPORTANCE: HHV-6 infection has
      been related to neuroinflammatory diseases; however, the lack of a suitable small
      animal infection model has considerably hampered further studies of HHV-6-induced
      neuropathogenesis. In this study, we have characterized a new model for HHV-6
      infection in mice expressing the human CD46 protein. Infection of CD46 transgenic
      mice with HHV-6A resulted in long-term persistence of viral DNA in the brains of
      infected animals and was followed by lymphocyte infiltration and upregulation of
      the CCL5 chemokine in the absence of clinical signs of disease. The secretion of
      a panel of chemokines was increased after infection in primary murine brain glial
      cultures, and the HHV-6-induced chemokine expression was inhibited when TLR9
      signaling was blocked. These results describe the first murine model for HHV-6A
      induced brain infection and suggest the importance of the TLR9 pathway in HHV-6A
      initiated neuroinflammation.

PMID- 24574406
TI  - Functional analysis of nuclear localization signals in VP1-2 homologues from all
      herpesvirus subfamilies.
AB  - The herpes simplex virus (HSV) tegument protein VP1-2 contains an N-terminal
      nuclear localization signal (NLS) that is critical for capsid routing to the
      nuclear pore. Here we analyzed positionally conserved determinants in VP1-2
      homologues from each of the alpha, beta, and gamma classes of human
      herpesviruses. The overall architectures of the VP1-2s were similar, with a
      conserved N-terminal ubiquitin-specific protease domain separated from an
      internal region by a linker that was quite poorly conserved in length and
      sequence. Within this linker region all herpesviruses contained a conserved,
      highly basic motif which nevertheless exhibited distinct class-specific features.
      The motif in HSV functioned as a monopartite NLS, while in varicella-zoster virus
      (VZV) activity required an adjacent basic section defining the motif as a
      bipartite NLS. Neither the beta- nor gammaherpesvirus VP1-2 motifs were
      identified by prediction algorithms, but they nevertheless functioned as
      efficient NLS motifs both in heterologous transfer assays and in HSV VP1-2.
      Furthermore, though with different efficiencies and with the exception of human
      herpesvirus 8 (HHV-8), these chimeric variants rescued the replication defect of
      an HSV mutant lacking its NLS motif. We demonstrate that the lysine at position
      428 of HSV is critical for replication, with a single alanine substitution being
      sufficient to abrogate NLS function and virus growth. We conclude that the basic
      motifs of each of the VP1-2 proteins are likely to confer a similar function in
      capsid entry in the homologous setting and that while there is flexibility in the
      exact type of motif employed, specific individual residues are critical for
      function. IMPORTANCE: To successfully infect cells, all herpesviruses, along with
      many other viruses, e.g., HIV, hepatitis B virus, and influenza virus, must
      navigate through the cytoplasmic environment and dock with nuclear pores for
      transport of their genomes into the nucleus. However, we still have a limited
      understanding of the detailed mechanisms involved. Insight into these events is
      needed and could offer opportunities for therapeutic intervention. This work
      investigated the role of a specific determinant in the structural protein VP1-2
      in herpesvirus entry. We examined this determinant in representative VP1-2s from
      all herpesvirus subfamilies, demonstrated NLS function, dissected key residues,
      and showed functional relevance in rescuing replication of the mutant blocked in
      capsid navigation to the pore. The results are important and strongly support our
      conclusions of the generality that these motifs are crucial for entry of all
      herpesviruses. They also facilitate future analysis on selective host
      interactions and possible routes to disrupt function.

PMID- 24574407
TI  - Role of poultry in the spread of novel H7N9 influenza virus in China.
AB  - The recent outbreak of H7N9 influenza in China has resulted in many human cases
      with a high fatality rate. Poultry are the likely source of infection for humans
      on the basis of sequence analysis and virus isolations from live bird markets,
      but it is not clear which species of birds are most likely to be infected and
      shedding levels of virus sufficient to infect humans. Intranasal inoculation of
      chickens, Japanese quail, pigeons, Pekin ducks, Mallard ducks, Muscovy ducks, and
      Embden geese with 10(6) 50% egg infective doses of the A/Anhui/1/2013 virus
      resulted in infection but no clinical disease signs. Virus shedding was much
      higher and prolonged in quail and chickens than in the other species. Quail
      effectively transmitted the virus to direct contacts, but pigeons and Pekin ducks
      did not. In all species, virus was detected at much higher titers from
      oropharyngeal swabs than cloacal swabs. The hemagglutinin gene from samples
      collected from selected experimentally infected birds was sequenced, and three
      amino acid differences were commonly observed when the sequence was compared to
      the sequence of A/Anhui/1/2013: N123D, N149D, and L217Q. Leucine at position 217
      is highly conserved for human isolates and is associated with alpha2,6-sialic
      acid binding. Different amino acid combinations were observed, suggesting that
      the inoculum had viral subpopulations that were selected after passage in birds.
      These experimental studies corroborate the finding that certain poultry species
      are reservoirs of the H7N9 influenza virus and that the virus is highly tropic
      for the upper respiratory tract, so testing of bird species should preferentially
      be conducted with oropharyngeal swabs for the best sensitivity. IMPORTANCE: The
      recent outbreak of H7N9 influenza in China has resulted in a number of human
      infections with a high case fatality rate. The source of the viral outbreak is
      suspected to be poultry, but definitive data on the source of the infection are
      not available. This study provides experimental data to show that quail and
      chickens are susceptible to infection, shed large amounts of virus, and are
      likely important in the spread of the virus to humans. Other poultry species can
      be infected and shed virus but are less likely to play a role of transmitting the
      virus to humans. Pigeons were previously suggested to be a possible source of the
      virus because of isolation of the virus from several pigeons in poultry markets
      in China, but experimental studies show that they are generally resistant to
      infection and are unlikely to play a role in the spread of the virus.

PMID- 24574408
TI  - Local control of repeated-dose rectal challenges in DNA/MVA-vaccinated macaques
      protected against a first series of simian immunodeficiency virus challenges.
AB  - Here, we report the results of a late boost and three additional series of simian
      immunodeficiency virus (SIV) challenges in seven DNA/modified vaccinia virus
      Ankara (MVA)-vaccinated rhesus macaques who resisted a first series of rectal
      challenges. During 29 additional challenges delivered over 2.3 years, all animals
      became infected. However, 13 blips of virus in six macaques and anamnestic Env
      specific rectal IgA responses in three of the six suggested that local control of
      infections was occurring during the serial challenge. 

PMID- 24574409
TI  - PrP expression level and sensitivity to prion infection.
AB  - Mice overexpressing the prion protein (PrP) sequence from various host species
      are widely used for measuring infectious titers in prion disease. However, the
      impact that the transgene expression level might have on the susceptibility to
      infection raises some concerns about the final biological relevance of these
      models. Here we report that endpoint titration of a sheep scrapie isolate in
      sheep and in mice overexpressing the ovine PrP results in similar estimates of
      the infectious titer. 

PMID- 24574410
TI  - Brown planthopper nudivirus DNA integrated in its host genome.
AB  - The brown planthopper (BPH), Nilaparvata lugens (Hemiptera:Delphacidae), is one
      of the most destructive insect pests of rice crops in Asia. Nudivirus-like
      sequences were identified during the whole-genome sequencing of BPH. PCR
      examination showed that the virus sequences were present in all of the 22 BPH
      populations collected from East, Southeast, and South Asia. Thirty-two of the 33
      nudivirus core genes were identified, including 20 homologues of baculovirus core
      genes. In addition, several gene clusters that were arranged collinearly with
      those of other nudiviruses were found in the partial virus genome. In a
      phylogenetic tree constructed using the supermatrix method, the original virus
      was grouped with other nudiviruses and was closely related to polydnavirus. Taken
      together, these data indicated that the virus sequences belong to a new member of
      the family Nudiviridae. More specifically, the virus sequences were integrated
      into the chromosome of its insect host during coevolution. This study is the
      first report of a large double-stranded circular DNA virus genome in a sap
      sucking hemipteran insect. IMPORTANCE: This is the first report of a large double
      stranded DNA virus integrated genome in the planthopper, a plant sap-sucking
      hemipteran insect. It is an exciting addition to the evolutionary story of
      bracoviruses (polydnaviruses), nudiviruses, and baculoviruses. The results on the
      virus sequences integrated in the chromosomes of its insect host also represent a
      story of successful coevolution of an invertebrate virus and a plant sap-sucking
      insect.

PMID- 24574411
TI  - The stability of herpes simplex virus 1 ICP0 early after infection is defined by
      the RING finger and the UL13 protein kinase.
AB  - Herpes simplex virus 1 (HSV-1)-infected cell protein 0 (ICP0) is a
      multifunctional protein that plays a key role in overcoming numerous facets of
      host innate immunity. A key function of ICP0 that requires an intact RING finger
      domain is that of an ubiquitin E3 ligase: ICP0 interacts with at least three
      ubiquitin-conjugating enzymes of which one, UbcH5a, is required for degradation
      of PML and SP100. A preceding report showed that ICP0 is highly unstable at very
      early times after infection but becomes stable at later times. We report here
      that (i) the degradation of ICP0 is not infected cell specific, (ii) the
      degradation does not require the interaction of ICP0 with either UbcH5a, UbcH6,
      or UbcH9, (iii) ICP0 is degraded both early and late in cells infected with a
      mutant lacking the UL13 protein kinase, (iv) ICP0 encoded by wild-type virus or
      the DeltaUL13 mutant is stable in cells transfected with a plasmid encoding UL13
      before infection, (v) ICP0 carrying mutations in the RING finger domain is stable
      both early and late in infection, and, finally, (vi) in cells infected with both
      wild type and RING finger mutant only the wild-type ICP0 is rapidly degraded at
      early times. The results suggest that the stability of ICP0 is mediated by the
      UL13 protein kinase and that the target of proteolysis is a site at or near the
      RING domain of ICP0. IMPORTANCE: ICP0, a major regulatory protein of HSV-1, turns
      over rapidly early in infection but becomes stable at late times. We report that
      stabilization requires the presence of UL13 protein kinase and that an ICP0 with
      mutations in RING finger is stable. In mixed infections mutant ICP0 is stable,
      whereas the wild-type ICP0 is degraded. Our findings suggest that the lifestyle
      of HSV-1 requires an ICP0 that turns over rapidly if late proteins are absent.

PMID- 24574412
TI  - Identification of alternative transcripts encoding the essential murine
      gammaherpesvirus lytic transactivator RTA.
AB  - The essential immediate early transcriptional activator RTA, encoded by gene 50,
      is conserved among all characterized gammaherpesviruses. Analyses of a
      recombinant murine gammaherpesvirus 68 (MHV68) lacking both of the known gene 50
      promoters (G50DblKo) revealed that this mutant retained the ability to replicate
      in the simian kidney epithelial cell line Vero but not in permissive murine
      fibroblasts following low-multiplicity infection. However, G50DblKo replication
      in permissive fibroblasts was partially rescued by high-multiplicity infection.
      In addition, replication of the G50DblKo virus was rescued by growth on mouse
      embryonic fibroblasts (MEFs) isolated from IFN-alpha/betaR-/- mice, while growth
      on Vero cells was suppressed by the addition of alpha interferon (IFN-alpha). 5'
      rapid amplification of cDNA ends (RACE) analyses of RNAs prepared from G50DblKo
      and wild-type MHV68-infected murine macrophages identified three novel gene 50
      transcripts initiating from 2 transcription initiation sites located upstream of
      the currently defined proximal and distal gene 50 promoters. In transient
      promoter assays, neither of the newly identified gene 50 promoters exhibited
      sensitivity to IFN-alpha treatment. Furthermore, in a single-step growth analysis
      RTA levels were higher at early times postinfection with the G50DblKo mutant than
      with wild-type virus but ultimately fell below the levels of RTA expressed by
      wild-type virus at later times in infection. Infection of mice with the MHV68
      G50DblKo virus demonstrated that this mutant virus was able to establish latency
      in the spleen and peritoneal exudate cells (PECs) of C57BL/6 mice with about 1/10
      the efficiency of wild-type virus or marker rescue virus. However, despite the
      ability to establish latency, the G50DblKo virus mutant was severely impaired in
      its ability to reactivate from either latently infected splenocytes or PECs.
      Consistent with the ability to rescue replication of the G50DblKo mutant by
      growth on type I interferon receptor null MEFs, infection of IFN-alpha/betaR-/-
      mice with the G50DblKo mutant virus demonstrated partial rescue of (i) acute
      virus replication in the lungs, (ii) establishment of latency, and (iii)
      reactivation from latency. The identification of additional gene 50/RTA
      transcripts highlights the complex mechanisms involved in controlling expression
      of RTA, likely reflecting time-dependent and/or cell-specific roles of different
      gene 50 promoters in controlling virus replication. Furthermore, the newly
      identified gene 50 transcripts may also act as negative regulators that modulate
      RTA expression. IMPORTANCE: The viral transcription factor RTA, encoded by open
      reading frame 50 (Orf50), is well conserved among all known gammaherpesviruses
      and is essential for both virus replication and reactivation from latently
      infected cells. Previous studies have shown that regulation of gene 50
      transcription is complex. The studies reported here describe the presence of
      additional alternatively initiated, spliced transcripts that encode RTA.
      Understanding how expression of this essential viral gene product is regulated
      may identify new strategies for interfering with infection in the setting of
      gammaherpesvirus-induced diseases.

PMID- 24574413
TI  - Anti-lyssaviral activity of interferons kappa and omega from the serotine bat,
      Eptesicus serotinus.
AB  - Interferons (IFNs) are cytokines produced by host cells in response to the
      infection with pathogens. By binding to the corresponding receptors, IFNs trigger
      different pathways to block intracellular replication and growth of pathogens and
      to impede the infection of surrounding cells. Due to their key role in host
      defense against viral infections, as well as for clinical therapies, the IFN
      responses and regulation mechanisms are well studied. However, studies of type I
      IFNs have mainly focused on alpha interferon (IFN-alpha) and IFN-beta subtypes.
      Knowledge of IFN-kappa and IFN-omega is limited. Moreover, most studies are
      performed in humans or mouse models but not in the original host of zoonotic
      pathogens. Bats are important reservoirs and transmitters of zoonotic viruses
      such as lyssaviruses. A few studies have shown an antiviral activity of IFNs in
      fruit bats. However, the function of type I IFNs against lyssaviruses in bats has
      not been studied yet. Here, IFN-kappa and IFN-omega genes from the European
      serotine bat, Eptesicus serotinus, were cloned and functionally characterized. E.
      serotinus IFN-kappa and IFN-omega genes are intronless and well conserved between
      microchiropteran species. The promoter regions of both genes contain essential
      regulatory elements for transcription factors. In vitro studies indicated a
      strong activation of IFN signaling by recombinant IFN-omega, whereas IFN-kappa
      displayed weaker activation. Noticeably, both IFNs inhibit to different extents
      the replication of different lyssaviruses in susceptible bat cell lines. The
      present study provides functional data on the innate host defense against
      lyssaviruses in endangered European bats. IMPORTANCE: We describe here for the
      first time the molecular and functional characterization of two type I
      interferons (IFN-kappa and -omega) from European serotine bat (Eptesicus
      serotinus). The importance of this study is mainly based on the fact that very
      limited information about the early innate immune response against bat
      lyssaviruses in their natural host serotine bats is yet available. Generally,
      whereas the antiviral activity of other type I interferons is well studied, the
      functional involvement of IFN-kappa and -omega has not yet been investigated.

PMID- 24574414
TI  - Genome scale patterns of recombination between coinfecting vaccinia viruses.
AB  - Recombination plays a critical role in virus evolution. It helps avoid genetic
      decline and creates novel phenotypes. This promotes survival, and genome
      sequencing suggests that recombination has facilitated the evolution of human
      pathogens, including orthopoxviruses such as variola virus. Recombination can
      also be used to map genes, but although recombinant poxviruses are easily
      produced in culture, classical attempts to map the vaccinia virus (VACV) genome
      this way met with little success. We have sequenced recombinants formed when VACV
      strains TianTan and Dryvax are crossed under different conditions. These were a
      single round of growth in coinfected cells, five rounds of sequential passage, or
      recombinants obtained using leporipoxvirus-mediated DNA reactivation. Our studies
      showed that recombinants contain a patchwork of DNA, with the number of exchanges
      increasing with passage. Further passage also selected for TianTan DNA and
      correlated with increased plaque size. The recombinants produced through a single
      round of coinfection contain a disproportionate number of short conversion tracks
      (<1 kbp) and exhibited 1 exchange per 12 kbp, close to the ~1 per 8 kbp in the
      literature. One by-product of this study was that rare mutations were also
      detected; VACV replication produces ~1*10(-8) mutation per nucleotide copied per
      cycle of replication and ~1 large (21 kbp) deletion per 70 rounds of passage.
      Viruses produced using DNA reactivation appeared no different from recombinants
      produced using ordinary methods. An attractive feature of this approach is that
      when it is combined with selection for a particular phenotype, it provides a way
      of mapping and dissecting more complex virus traits. IMPORTANCE: When two closely
      related viruses coinfect the same cell, they can swap genetic information through
      a process called recombination. Recombination produces new viruses bearing
      different combinations of genes, and it plays an important role in virus
      evolution. Poxviruses are a family of viruses that includes variola (or smallpox)
      virus, and although poxviruses are known to recombine, no one has previously
      mapped the patterns of DNAs exchanged between viruses. We coinfected cells with
      two different vaccinia poxviruses, isolated the progeny, and sequenced them. We
      show that poxvirus recombination is a very accurate process that assembles
      viruses containing DNA copied from both parents. In a single round of infection,
      DNA is swapped back and forth ~18 times per genome to make recombinant viruses
      that are a mosaic of the two parental DNAs. This mixes many different genes in
      complex combinations and illustrates how recombination can produce viruses with
      greatly altered disease potential.

PMID- 24574417
TI  - Use of flexible esophagoscopy by otolaryngologists.
AB  - OBJECTIVES: We used questionnaires to determine current practice patterns for
      esophagoscopy by otolaryngologists in the United States, with attention to
      foreign body management. METHODS: A 10-item questionnaire designed to determine
      the prevalence of flexible esophagoscopy use among otolaryngologists, with a
      particular focus on foreign body removal, was created and sent via e-mail to all
      members of the American Academy of Otolaryngology-Head and Neck Surgery. A
      second, 6-question survey to assess the level of resident training in flexible
      esophagoscopy was similarly created and sent to all directors of US
      otolaryngology residency programs. RESULTS: There were a total of 160 respondents
      to the first survey from all geographic regions, most of whom were in group
      private practice. Overall, only 21.3% of the respondents were trained to perform
      flexible esophagoscopy during residency, whereas 43% of those who graduated after
      1990 received this training. Most respondents performed flexible esophagoscopy
      without sedation in the office setting. The most common indications were
      evaluation of dysphagia, screening for complications of laryngopharyngeal reflux,
      and panendoscopy for head and neck cancer. Nearly 70% of the respondents were
      either primarily responsible for foreign body management at their institution or
      shared this responsibility with a gastroenterology department. Eighty-four
      percent used the rigid esophagoscope alone for this purpose. More than three
      quarters of otolaryngology residency programs currently include flexible
      esophagoscopy in their training, which is performed equally in the operating room
      and in the office; most favor rigid esophagoscopy for foreign body retrieval but
      use both techniques. CONCLUSIONS: There has been a rapid increase in the use of
      flexible esophagoscopy by otolaryngologists. The majority of residency programs
      currently include flexible esophagoscopy in their training. Otolaryngologists
      play a major role in esophageal foreign body management and primarily use the
      rigid esophagoscope for this purpose.

PMID- 24574415
TI  - Upolu virus and Aransas Bay virus, two presumptive bunyaviruses, are novel
      members of the family Orthomyxoviridae.
AB  - Emerging and zoonotic pathogens pose continuing threats to human health and
      ongoing challenges to diagnostics. As nucleic acid tests are playing increasingly
      prominent roles in diagnostics, the genetic characterization of molecularly
      uncharacterized agents is expected to significantly enhance detection and
      surveillance capabilities. We report the identification of two previously
      unrecognized members of the family Orthomyxoviridae, which includes the influenza
      viruses and the tick-transmitted Thogoto and Dhori viruses. We provide
      morphological, serologic, and genetic evidence that Upolu virus (UPOV) from
      Australia and Aransas Bay virus (ABV) from North America, both previously
      considered potential bunyaviruses based on electron microscopy and
      physicochemical features, are orthomyxoviruses instead. Their genomes show up to
      68% nucleotide sequence identity to Thogoto virus (segment 2; ~74% at the amino
      acid level) and a more distant relationship to Dhori virus, the two prototype
      viruses of the recognized species of the genus Thogotovirus. Despite sequence
      similarity, the coding potentials of UPOV and ABV differed from that of Thogoto
      virus, instead being like that of Dhori virus. Our findings suggest that the tick
      transmitted viruses UPOV and ABV represent geographically distinct viruses in the
      genus Thogotovirus of the family Orthomyxoviridae that do not fit in the two
      currently recognized species of this genus. IMPORTANCE: Upolu virus (UPOV) and
      Aransas Bay virus (ABV) are shown to be orthomyxoviruses instead of bunyaviruses,
      as previously thought. Genetic characterization and adequate classification of
      agents are paramount in this molecular age to devise appropriate surveillance and
      diagnostics. Although more closely related to Thogoto virus by sequence, UPOV and
      ABV differ in their coding potentials by lacking a proposed pathogenicity factor.
      In this respect, they are similar to Dhori virus, which, despite the lack of a
      pathogenicity factor, can cause disease. These findings enable further studies
      into the evolution and pathogenicity of orthomyxoviruses.

PMID- 24574418
TI  - Simulation model for tracheotomy education for primary health-care providers.
AB  - OBJECTIVES: We performed this study to evaluate the competency of health-care
      providers managing patients with tracheotomies, and assess the need for, and
      efficacy of, a multidisciplinary educational program incorporating patient
      simulation. METHODS: The prospective observational study included 87 subjects who
      manage patients with tracheotomies within a tertiary-care hospital. The subjects
      completed self-assessment questionnaires and objective multiple-choice tests
      before and after attending a comprehensive educational course using patient
      simulation. The outcome measurements included pre-course and post-course
      questionnaire and test scores, as well as observational data collected during
      recorded patient simulation sessions. RESULTS: Before the education and
      simulation, the subjects reported an average comfort level of 3.3 on a 5-point
      Likert scale across 10 categories in the questionnaire, which improved to 4.4
      after the training (p < 0.0001). The subjects' mean scores improved from 56% on
      the pre-course test to 91% on the post-course test (p < 0.0001). The specific
      deficiencies observed during patient simulation scenarios included unfamiliarity
      with different tracheotomy tube types, misunderstanding of speaking valve
      physiology, and delayed recognition and treatment of a plugged or dislodged
      tracheotomy tube. CONCLUSIONS: There is a significant need for improved
      tracheotomy education among primary health-care providers. Incorporating patient
      simulation into a comprehensive tracheotomy educational program was effective in
      improving provider confidence, increasing provider knowledge, and teaching the
      skills necessary for managing patients with a tracheotomy.

PMID- 24574416
TI  - Nelfinavir inhibits maturation and export of herpes simplex virus 1.
AB  - Nelfinavir (NFV) is an HIV-1 protease inhibitor with demonstrated antiviral
      activity against herpes simplex virus 1 (HSV-1) and several other herpesviruses.
      However, the stages of HSV-1 replication inhibited by NFV have not been explored.
      In this study, we investigated the effects of NFV on capsid assembly and
      envelopment. We confirmed the inhibitory effects of NFV on HSV-1 replication by
      plaque assay and found that treatment with NFV did not affect capsid assembly,
      activity of the HSV-1 maturational protease, or formation of DNA-containing
      capsids in the nucleus. Confocal and electron microscopy studies showed that
      these capsids were transported to the cytoplasm but failed to complete secondary
      envelopment and subsequent exit from the cell. Consistent with the microscopy
      results, a light-scattering band corresponding to enveloped virions was not
      evident following sucrose gradient rate-velocity separation of lysates from drug
      treated cells. Evidence of a possibly related effect of NFV on viral glycoprotein
      maturation was also discovered. NFV also inhibited the replication of an HSV-1
      thymidine kinase mutant resistant to nucleoside analogues such as acyclovir.
      Given that NFV is neither a nucleoside mimic nor a known inhibitor of nucleic
      acid synthesis, this was expected and suggests its potential as a coinhibitor or
      alternate antiviral therapeutic agent in cases of resistance. IMPORTANCE:
      Nelfinavir (NFV) is a clinically important antiviral drug that inhibits
      production of infectious HIV. It was reported to inhibit herpesviruses in cell
      culture. Herpes simplex virus 1 (HSV-1) infections are common and often
      associated with several diseases. The studies we describe here confirm and extend
      earlier findings by investigating how NFV interferes with HSV-1 replication. We
      show that early steps in virus formation (e.g., assembly of DNA-containing
      capsids in the nucleus and their movement into the cytoplasm) appear to be
      unaffected by NFV, whereas later steps (e.g., final envelopment in the cytoplasm
      and release of infectious virus from the cell) are severely restricted by the
      drug. Our findings provide the first insight into how NFV inhibits HSV-1
      replication and suggest that this drug may have applications for studying the
      herpesvirus envelopment process. Additionally, NFV may have therapeutic value
      alone or in combination with other antivirals in treating herpesvirus infections.

PMID- 24574419
TI  - Chronic cervical esophageal foreign bodies in children: surgical approach after
      unsuccessful endoscopic management.
AB  - OBJECTIVES: We reviewed the surgical management of chronic cervical esophageal
      foreign bodies (CCEFBs) in a pediatric population after failed endoscopic
      retrieval. METHODS: A descriptive analysis via a retrospective chart review of
      patients with CCEFBs who failed initial endoscopic management was performed
      between 2008 and 2013. Details were recorded regarding presenting symptoms, time
      from symptom onset to diagnosis of the CCEFB, surgical approach, and
      complications. RESULTS: Three patients with CCEFBs unsuccessfully managed with
      endoscopy were identified. The range of ages at diagnosis was 14 months to 4.5
      years. The foreign bodies (FBs) were present for at least 1 month before
      diagnosis (range, 1 to 10 months). Respiratory symptoms were predominant in all
      cases. Neck exploration with removal of the FB was performed in each case.
      Complications included esophageal stricture necessitating serial dilations
      (patient 1), left true vocal fold paresis that resolved spontaneously (patient
      3), and tracheoesophageal fistula with successful endoscopic closure (patient 3).
      No long-term sequelae were experienced. CONCLUSIONS: A high index of suspicion is
      required to recognize CCEFBs in children with respiratory distress. Although
      endoscopic management remains the first-line treatment, it may fail or may not be
      possible because of transmural FB migration. In this setting, neck exploration
      with FB removal is a safe and effective alternative.

PMID- 24574420
TI  - Microscopic examination of iatrogenic subglottic tracheal stenosis: observations
      that may elucidate its histopathologic origin.
AB  - OBJECTIVES: The histopathologic origin of iatrogenic subglottic tracheal stenosis
      (ISTS) remains unclear. The purpose of this study was to use detailed operative
      microscopy to systematically examine the operative en bloc specimens of patients
      with ISTS and to observe the histologic and morphological changes in the hopes
      that these observations will provide insight into the histopathologic origin of
      these devastating injuries. METHODS: The operative specimens of 18 patients who
      underwent open tracheal or laryngotracheal resection for ISTS were examined.
      Precise morphological characteristics were investigated for each tissue layer,
      including the adventitia, the outer surface of the perichondrium, the cartilage,
      the inner surface of the perichondrium, the submucosa, and the mucosa. Each
      tissue layer was evaluated independently and in relationship to the other layers.
      The cartilaginous airway was further evaluated relative to the pars membranacea.
      RESULTS: The most common morphological finding in the epithelium was squamous
      metaplasia with occasional intense inflammation visible in the underlying mucosa,
      including cicatrization. The underlying cartilage demonstrated ossific metaplasia
      with sequestration in many cases. By far the most pronounced changes were found
      in the outer perichondrium and overlying adventitia and included diffuse
      paucicellular or hyperplastic fibrosis with intense hyperplastic scar formation
      or hyaline cicatrization. In the pars membranacea, severe scar formation and
      hyperplastic fibrosis were predominant. Ossific metaplasia was particularly
      severe in the lateral or outer parts of the tracheal ring, particularly in the
      vicinity of the adventitia and outer perichondrium. These changes were much more
      pronounced than the relatively minor changes observed in the submucosa and
      mucosa. CONCLUSIONS: The most severe pathologic observations occurred in the
      lateral tissue layers, ie, the outer perichondrium and adventia. Given that an
      injury occurs from the tracheal lumen, these tissue layers have the greatest
      distance from the site of injury. As only minor changes occurred in the inner
      tissue layers, we hypothesize that these tissues have a greater regenerative
      capacity than the outer layers. This study supports the theory that the depth of
      the airway injury is more critical to the development of ISTS than is the extent
      or length of the injury.

PMID- 24574421
TI  - Relapse patterns after transoral laser microsurgery and postoperative irradiation
      for squamous cell carcinomas of the tonsil and tongue base.
AB  - OBJECTIVES: We evaluated relapse patterns after transoral laser microsurgery
      (TLM) in squamous cell carcinoma (SCC) of the tonsil and tongue base and
      evaluated the indications for adjuvant irradiation. METHODS: Between December 1,
      1996, and December 31, 2005, 79 patients with previously untreated SCC of the
      tonsil or tongue base underwent TLM with or without neck dissection. Thirty-eight
      patients (48%) underwent postoperative irradiation (median, 62 Gy) to the primary
      site and the neck. Analysis of relapse patterns was performed on the basis of
      adverse risk factors and the presence or absence of adjuvant irradiation.
      RESULTS: The median follow-up for living patients was 47 months (range, 10 to 107
      months), and patients were monitored for at least 2 years or until recurrence or
      death. Local, regional, and distant treatment failures numbered 4, 6, and 4 for
      surgery alone (n = 41) and 0, 2, and 6 for adjuvant irradiation (n = 38),
      respectively. Patients with high-risk features (extracapsular extension or at
      least 2 adverse factors) had locoregional control rates at 2 or more years of 66%
      and 94% for TLM alone and TLM plus adjuvant irradiation, respectively.
      CONCLUSIONS: Adjuvant irradiation after TLM resection of oropharyngeal SCC with
      intermediate- or high-risk features improves locoregional control compared with
      TLM alone.

PMID- 24574422
TI  - Effect of uvulopalatopharyngoplasty on leptin and endothelial function in sleep
      apnea.
AB  - OBJECTIVES: This study evaluated the effects of uvulopalatopharyngoplasty (UPPP)
      on serum leptin levels and endothelial function in patients with obstructive
      sleep apnea syndrome (OSAS). METHODS: Fifteen healthy subjects and 35 patients
      with moderate to severe OSAS who desired UPPP were prospectively enrolled. The
      serum levels of leptin and nitric oxide derivative (NOx) from their peripheral
      blood samples were measured by enzyme-linked immunosorbent assay. All subjects
      participated in sleep studies, which were repeated 3 months after UPPP in the
      patients with OSAS. RESULTS: Before UPPP, the patients with OSAS had a higher
      serum level of leptin and a lower NOx level than did the control subjects. The
      serum leptin levels in the 17 of the 35 patients with OSAS who were surgical
      responders decreased from 24.2 +/- 6.1 ng/mL before operation to 15.9 +/- 6.0
      ng/mL after operation. The serum NOx levels in these 17 patients increased from
      18.5 +/- 7.5 umol/L before operation to 27.3 +/- 8.2 umol/L after operation. In
      the 18 patients who were unresponsive to surgery, the serum leptin and NOx levels
      remained impaired after the UPPP. CONCLUSIONS: Successful treatment of OSAS with
      UPPP leads to the normalization of serum leptin and NOx levels.

PMID- 24574423
TI  - Alternative to canal wall-down mastoidectomy for sclerotic mastoid cavities:
      epitympanoplasty with mastoid obliteration.
AB  - OBJECTIVES: Surgical procedures for chronic ear disease can be grossly divided
      into two tympanoplasty procedures: canal wall-up and canal wall-down (CWD)
      mastoidectomies. The choice depends on the surgeon's preference. Epitympanoplasty
      with mastoid obliteration (EMO) has shown postoperative results similar to those
      of CWD mastoidectomy with long-term follow-up. In this study, we compared the
      outcomes of EMO and CWD mastoidectomy in preoperatively sclerotic mastoid
      cavities with cholesteatoma, chronic otitis media with poor eustachian tube
      function, or adhesive otitis media. The operations were performed by the same
      surgeons in order to eliminate any effect of surgeon preference on the surgical
      outcomes. METHODS: We reviewed the medical records of patients who underwent
      tympanoplasty with EMO (EMO group) or CWD mastoidectomy (CWD group) and followed
      them for more than 28 months. The postoperative outcomes were analyzed and
      compared. RESULTS: The EMO and CWD groups comprised 132 and 110 ears,
      respectively. In both groups, the air-bone gaps were significantly reduced after
      operation. The relapse rates of the groups were similar. Cavity problems were the
      most common complication in the CWD group. The overall complication rate in the
      EMO group was significantly lower than that in the CWD group (p = 0.044).
      CONCLUSIONS: Epitympanoplasty with mastoid obliteration can be considered an
      alternative procedure to CWD mastoidectomy in patients with preoperatively
      sclerotic mastoid cavities. It gives similar surgical results and has fewer
      complications.

PMID- 24574424
TI  - Early and severe dyspnea after supracricoid partial laryngectomy.
AB  - We present the case of a not-yet-reported complication that occurred during the
      immediate postoperative period after supracricoid partial laryngectomy. We
      include a review of the literature on complications following this procedure,
      emphasizing technical considerations that are critical during this surgery.
      Clinical, diagnostic, and operative findings are presented, as is a differential
      diagnosis for early and severe postoperative dyspnea following supracricoid
      laryngectomy. 

PMID- 24574425
TI  - Lipomas of the internal auditory canal and cerebellopontine angle.
AB  - OBJECTIVES: Lipomas of the internal auditory canal (IAC) and cerebellopontine
      angle (CPA) are exceedingly rare lesions. The purpose of this report was to
      describe our experience with lipomas of the IAC and CPA and perform a review of
      the literature. METHODS: We report 8 cases of lipomas involving the IAC and/or
      the CPA that were managed at Gruppo Otologico between April 1987 and October
      2012. RESULTS: Four cases of entirely intracanalicular lipomas were
      radiologically misinterpreted as vestibular schwannomas and underwent tumor
      removal by a translabyrinthine approach. Two of these patients experienced
      postoperative facial nerve palsy. Lipomas were suspected in 4 patients on the
      basis of imaging findings and were managed conservatively. Of these 4 cases, 3
      did not show any growth after an average period of 28 months, and 1 case
      demonstrated tumor growth on follow-up imaging. CONCLUSIONS: Neuroimaging
      represents an extremely important tool for this diagnosis. Attempts to achieve
      complete resection may result in severe neurologic sequelae, especially in large
      lesions. Observation with repeated imaging in order to detect growth of the
      lesion is usually recommended. Debulking of the tumor, mainly aimed at brain stem
      and cranial nerve decompression, should be considered in cases of disabling and
      uncontrolled neurologic symptoms and signs.

PMID- 24574426
TI  - Inflammatory protein expression in human subglottic stenosis tissue mirrors that
      in a murine model.
AB  - OBJECTIVES: We undertook to describe the genetic and protein composition of
      subglottic stenosis (SGS) by measuring an array of protein expression and
      messenger RNA levels within human SGS tissue. We also sought to compare this
      human array to cytokine expression from a murine model of SGS in order to confirm
      the effective translational nature of our animal model. METHODS: Human
      granulation tissue from 10 patients with early symptomatic SGS was compared to
      control bronchus. The expression levels of 24 different cytokines were measured
      by a Luminex protein assay and real-time polymerase chain reaction. RESULTS: The
      protein expression in human SGS mirrors that seen in murine SGS. Transforming
      growth factor beta1, interleukin 1beta, and matrix metalloproteinase 9 were
      markedly elevated in both human and mouse SGS tissues. The protein array showed a
      statistically significant elevation in the proinflammatory cytokines tumor
      necrosis factor alpha, interleukin 1, granulocyte macrophage colony-stimulating
      factor, and interferon gamma. CONCLUSIONS: This is the first study, to our
      knowledge, to measure an array of protein expression within human SGS tissue. The
      expression profile suggests that symptomatic tracheal granulation tissue is
      mostly within the early inflammatory phase of wound healing and has only begun
      fibrotic and angiogenic remodeling. This study validates our murine model of SGS,
      and also helps to define the exact pathways of tissue injury, in the hope of
      leading to new treatments for this difficult condition.

PMID- 24574427
TI  - Bicarbonate availability for vocal fold epithelial defense to acidic challenge.
AB  - OBJECTIVES: Bicarbonate is critical for acid-base tissue homeostasis. In this
      study we investigated the role of bicarbonate ion transport in vocal fold
      epithelial defense to acid challenges. Acidic insults to the larynx are common in
      gastric reflux, carcinogenesis and metastasis, and acute inflammation. METHODS:
      Ion transport was measured in viable porcine vocal fold epithelium. First, 18
      vocal folds were exposed to either the carbonic anhydrase antagonist
      acetazolamide or to vehicle. Second, 32 vocal folds were exposed to either a
      control buffer or a bicarbonate-free buffer on their luminal or basolateral
      surface or both. Third, 32 vocal folds were challenged with acid in the presence
      of bicarbonate-free or control buffer. RESULTS: The vocal fold transepithelial
      resistance was greater than 300 Omega*cm(2), suggesting robust barrier integrity.
      Ion transport did not change after exposure to acetazolamide (p > 0.05). Exposure
      to bicarbonate-free buffer did not compromise vocal fold ion transport (p >
      0.05). Ion transport increased after acid challenge. This increase approached
      statistical significance and was the greatest for the control buffer and for the
      bicarbonate-free buffer applied to the basolateral surface. CONCLUSIONS:
      Bicarbonate secretion may contribute to vocal fold defense against acid
      challenge. Our data offer a potential novel role for bicarbonate as a therapeutic
      agent to reduce pH abnormalities in the larynx and prevent associated
      pathological changes.

PMID- 24574428
TI  - Sport club participation of adolescents with asthma: maternal factors and
      adolescent cognitions.
AB  - RATIONALE: Sport participation is especially important for patients with asthma
      in that it decreases psychosocial and physiological problems associated with
      inactivity. However, adolescents with asthma seem to participate less in sports
      compared to their non-asthmatic peers. The current study tested the direct
      associations between maternal sport-specific factors and sport club participation
      of early adolescents with asthma and the indirect effect through adolescent's
      sport-specific cognitions. METHODS: During home visits, 261 adolescents (aged 10
      15) completed questionnaires about self-efficacy, beliefs regarding sport
      participation, and their actual sport club participation. Their mothers reported
      their sport-specific support, beliefs about offspring's and own sport
      participation, their own levels of physical activity, and their self-efficacy to
      stimulate offspring to participate in sports. Path analyses were used to examine
      the direct and indirect associations of maternal sport-specific factors with
      adolescents sport club participation via adolescent sport-specific cognitions.
      RESULTS: Analyses showed that maternal sport-specific support (beta = 0.20, P =
      0.007) and self-efficacy to stimulate offspring to participate in sports (beta =
      0.20, P = 0.027) related positively to adolescents' sport club participation.
      Adolescents' self-efficacy (indirect effect = 0.09, SE = 3.01, P < 0.001)
      mediated the positive relation between maternal self-efficacy to stimulate
      offspring to participate in sport and adolescents' participation in sport clubs.
      CONCLUSION: Maternal sport-specific factors related to adolescents' sport club
      participation directly and indirectly through adolescents' sport-specific
      cognitions. Intervention programs should focus on maternal sport-specific support
      and self-efficacy and adolescents' self-efficacy to increase sport participation
      of adolescents with asthma.

PMID- 24574429
TI  - Zero tolerance against patriarchal norms? A cross-sectional study of Swedish
      physicians' attitudes towards young females requesting virginity certificates or
      hymen restoration.
AB  - Many countries, Sweden among them, lack professional guidelines and established
      procedures for responding to young females requesting virginity certificates or
      hymen restoration due to honour-related threats. The purpose of the present
      survey study was to further examine the attitudes of the Swedish healthcare
      professionals concerned towards young females requesting virginity certificates
      or hymen restorations. The study indicates that a small majority of Swedish
      general practitioners and gynaecologists would accommodate these patients, at
      least given certain circumstances. But a large minority of physicians would under
      no circumstances help the young females, regardless of speciality, years of
      practice within medicine, gender, or experience of the phenomenon. Their
      responses are similar to other areas where it has been claimed that society
      should adopt a zero tolerance policy against certain phenomena, for instance drug
      policy, where it has also been argued that society should never act in ways that
      express support for the practice in question. However, this argument is
      questionable. A more pragmatic approach would also allow for follow-ups and
      evaluation of virginity certificates and hymen restorations, as is demonstrated
      by the Dutch policy. Hence, there are some obvious advantages to this pragmatic
      approach compared to the restrictive one espoused by a large minority of Swedish
      physicians and Swedish policy-makers in this area. 

PMID- 24574430
TI  - The ontogeny of human pulmonary angiotensin-converting enzyme and its aberrant
      expression may contribute to the pathobiology of bronchopulmonary dysplasia
      (BPD).
AB  - INTRODUCTION: The mammalian lung possesses the highest level of angiotensin
      converting enzyme (ACE) amongst all the organs. ACE is known to generate
      angiotensin (AT)-II from AT-I and to regulate serum bradykinin level, thereby
      controlling blood pressure. Recent data, however, indicate a role for ACE derived
      AT-II in angiogenesis, pulmonary hypertension, and neonatal lung disease. The
      ontogeny of ACE in humans has not been investigated. We studied pulmonary ACE
      expression during human lung development and in human bronchopulmonary dysplasia
      (BPD). MATERIAL AND METHODS: Human fetal autopsy lung tissue representing all
      three trimesters (12, 13, 16, 18, 24, 34, 39, and 40 weeks of gestational age
      (WGA)), as well as from 1 to 10 years of age with no significant lung pathology
      were used. In addition lung sections of patients with BPD (n = 5) were selected.
      The slides were immunostained using an anti-ACE monoclonal antibody. The temporal
      and spatial pattern of ACE expression was contrasted to that of the pan
      endothelial marker CD31. Staining intensity was graded. RESULTS: Mildly diffuse
      and strong microvascular endothelial immunreactivity for ACE was seen in the
      human fetus as early as 12 WGA. ACE expression peaked at mid gestation and
      remained high throughout gestation and postnatally. In BPD lungs ACE endothelial
      staining was largely absent, and when focal staining was observed the intensity
      was weak. CONCLUSION: We established that ACE expression is present in the human
      fetal lung as early as 12 WGA, remains active pre- and postnatally, and ACE
      expression was downregulated in BPD lungs. We speculate that ACE may be involved
      in the process of lung development.

PMID- 24574431
TI  - Seven percent hypertonic saline--0.1% hyaluronic acid in infants with mild-to
      moderate bronchiolitis.
AB  - OBJECTIVES: Our study was aimed to evaluate the efficacy of 7% hypertonic saline
      and 0.1% hyaluronic acid (7% HS-HA) given by inhalation, in infants hospitalized
      for mild-to-moderate bronchiolitis. METHODS: In a double-blind controlled study,
      39 infants (23 boys) <7 months of age (median age 2 months) were enrolled and
      randomly assigned to receive either nebulized 7% HS-HA (7%NaCl + 0.1%HA) (n:21)
      or 0.9 normal saline (NS) (n:18) at a dose of 2.5 ml twice a day for 3 days. All
      infants were assigned a clinical severity score at admission and four times daily
      during hospitalization. Main outcome measures were number of days
      hospitalization, safety and daily reduction in the severity score. RESULTS: No
      difference was found between the two groups for clinical severity score at
      admission. One child in the study group and two in the NS group interrupted the
      study protocol; 19% of infants in the study group and 11% in the NS group had
      mild cough after the aerosol. The length of stay in the control group and
      treatment groups were 4.8 +/- 1.5 versus 4.1 +/- 1.9 days, respectively (P =
      0.09). There was a trend for shortening the hospitalization days in the treatment
      group by 14.6%. The use of NS in the control group was identified as an
      independent risk factor for length of hospital stay using the multivariate
      logistic regression model (P = 0.04). No difference was observed between the two
      groups for the clinical score reduction during the first 3 days hospitalization.
      CONCLUSIONS: 7% HS-HA is a safe and effective therapy in treating infants
      hospitalized for mild-to-moderate bronchiolitis.

PMID- 24574432
TI  - Effectiveness of long-term routine pulmonary function surveillance following
      pediatric hematopoietic stem cell transplantation.
AB  - INTRODUCTION: Pulmonary complications following hematopoietic stem cell
      transplantation (HSCT) are common and often subclinical. Thus, periodic pulmonary
      function testing (PFT) is mandatory. This study sought to evaluate the
      effectiveness of long-term PFT surveillance for children undergoing HSCT and
      identify potential risk factors. METHODS: We reviewed long-term PFT for HSCT
      patients at a tertiary pediatric center. Inclusion criteria were PFT prior to and
      at least once following HSCT. RESULTS: Fifty-seven patients performed 202
      spirometry and 193 plethysmographic maneuvers; 41 were tested during the first
      year after HSCT, but only 29 were evaluated consistently long term (2-12 years).
      FVC and FEV(1) decreased gradually suggesting a restrictive ventilatory defect:
      FVC % predicted [mean +/- SD] dropped from 91 +/- 14% to 85 +/- 17% after 0-24
      months and 80 +/- 19% beyond 2 years (P = 0.01) whereas FEV(1) dropped from 95 +/
      16% to 88 +/- 19% and 82 +/- 20%, respectively (P = 0.002). A slight reduction
      in TLC was observed. Those undergoing allogeneic HSCT had a greater decline in
      FVC (P = 0.025) and FEV(1) (P = 0.025) as did those conditioned with radiation,
      regarding both FVC (P = 0.003) and FEV(1) (P = 0.002). Decline occurred earlier
      (<=2 years) after chemotherapy compared with radiation. Seven children had severe
      irreversible obstruction at >2 years despite therapeutic intervention.
      CONCLUSIONS: Most survivors of childhood HSCT maintain almost normal pulmonary
      function although mild restrictive lung disease may develop, particularly
      following allogeneic HSCT and conditioning with radiation. Severe airways
      obstruction developed in a small minority. The surveillance protocol for PFT
      needs to be followed more stringently to enable intervention possibly before
      early subclinical changes progress and become irreversible.

PMID- 24574433
TI  - The Escherichia coli datA site promotes proper regulation of cell division.
AB  - In Escherichia coli inhibition of replication leads to a block of cell division.
      This checkpoint mechanism ensures that no cell divides without having two
      complete copies of the genome to pass on to the two daughter cells. The
      chromosomal datA site is a 1 kb region that contains binding sites for the DnaA
      replication initiator protein, and which contributes to the inactivation of DnaA.
      An excess of datA sites provided on plasmids has been found to lead to both a
      delay in initiation of replication and in cell division during exponential
      growth. Here we have investigated the effect of datA on the cell division block
      that occurs upon inhibition of replication initiation in a dnaC2 mutant. We found
      that this checkpoint mechanism was aided by the presence of datA. In cells where
      datA was deleted or an excess of DnaA was provided, cell division occurred in the
      absence of replication and anucleate cells were formed. This finding indicates
      that loss of datA and/or excess of DnaA protein promote cell division. This
      conclusion was supported by the finding that the lethality of the division
      compromised mutants ftsZ84 and ftsI23 was suppressed by deletion of datA, at the
      lowest non-permissive temperature. We propose that the cell division block that
      occurs upon inhibition of DNA replication is, at least in part, due to a drop in
      the concentration of the ATP-DnaA protein. 

PMID- 24574435
TI  - Authors' response: Pars planavitrectomy to repair retinal detachment following
      brachytherapy for uveal melanoma.

PMID- 24574434
TI  - The gene cluster of aureocyclicin 4185: the first cyclic bacteriocin of
      Staphylococcus aureus.
AB  - Staphylococcus aureus 4185 was previously shown to produce at least two
      bacteriocins. One of them is encoded by pRJ101. To detect the bacteriocin
      encoding gene cluster, an ~9160 kb region of pRJ101 was sequenced. In silico
      analyses identified 10 genes (aclX, aclB, aclI, aclT, aclC, aclD, aclA, aclF,
      aclG and aclH) that might be involved in the production of a novel cyclic
      bacteriocin named aureocyclicin 4185. The organization of these genes was quite
      similar to that of the gene cluster responsible for carnocyclin A production and
      immunity. Four putative proteins encoded by these genes (AclT, AclC, AclD and
      AclA) also exhibited similarity to proteins encoded by cyclic bacteriocin gene
      clusters. Mutants derived from insertion of Tn917-lac into aclC, aclF, aclH and
      aclX were affected in bacteriocin production and growth. AclX is a 205 aa
      putative protein not encoded by the gene clusters of other cyclic bacteriocins.
      AclX exhibits 50 % similarity to a permease and has five putative membrane
      spanning domains. Transcription analyses suggested that aclX is part of the
      aureocyclicin 4185 gene cluster, encoding a protein required for bacteriocin
      production. The aclA gene is the structural gene of aureocyclicin 4185, which
      shows 65 % similarity to garvicin ML. AclA is proposed to be cleaved off,
      generating a mature peptide with a predicted Mr of 5607 Da (60 aa). By homology
      modelling, AclA presents four alpha-helices, like carnocyclin A. AclA could not
      be found at detectable levels in the culture supernatant of a strain carrying
      only pRJ101. To our knowledge, this is the first report of a cyclic bacteriocin
      gene cluster in the genus Staphylococcus. 

PMID- 24574436
TI  - Enhanced depth imaging optical coherence tomography of the choroid in migraine
      patients: implications for the association of migraine and glaucoma.
AB  - AIM: To compare the choroidal thickness measurements obtained during the attack
      period and during the pain-free interval in migraine patients using enhanced
      depth imaging optical coherence tomography (OCT). METHODS: 58 eyes of 29 subjects
      with a diagnosis of migraine with or without aura were enrolled in this
      observational, cross-sectional study. Two OCT scans were performed for each
      patient, one during the peak period of the migraine attack and the other during
      the headache-free interval, using the enhanced depth imaging mode. Choroidal
      thicknesses were measured at the fovea, at three locations nasal and at three
      locations temporal to the fovea at 500 MUm intervals. RESULTS: In patients with
      unilateral headaches, the choroidal thickness measurements obtained during the
      attack period were significantly increased only in the eyes on the headache side
      (p<0.001) compared to basal levels. At the fovea, the choroidal thickness
      measured in the pain-free interval was 373.45 +/- 76.47 MUm (mean +/- SD), which
      increased to 408.80 +/- 77.70 MUm during the attack period (p<0.001). When the
      choroidal thickness measurements of patients with bilateral headaches were
      compared to basal levels, a statistically significant increase was observed at
      five out of the seven measured points in the right eyes (p<0.05) and at all seven
      measured points in the left eyes (p<0.05). CONCLUSIONS: Choroidal thickness was
      found to be significantly increased in migraine patients during the attack period
      when compared to basal levels. The possible implications of this finding on the
      association between migraine and glaucoma are discussed.

PMID- 24574437
TI  - Evaluation of mouse experimental autoimmune uveoretinitis by spectral domain
      optical coherence tomography.
AB  - AIMS: To evaluate the efficacy of spectral domain optical coherence tomography
      (SD-OCT) in monitoring the development of mouse experimental autoimmune
      uveoretinitis (EAU) as an animal model of endogenous uveitis, and to develop an
      OCT-based grading system for EAU severity. METHODS: C57BL/6 mice were immunised
      with human interphotoreceptor retinoid-binding protein (amino acid sequence 1-20)
      peptide and complete Freund's adjuvant to induce EAU. The development of EAU was
      monitored by SD-OCT serially throughout the disease course, and the images were
      graded from 1 to 4 and compared with the clinical and histopathological grades.
      RESULTS: SD-OCT images depicted retinal lamella structures including the inner
      segment/outer segment (IS/OS) line in normal mice. Retinal structural changes
      were observed on SD-OCT images in mice that developed EAU clinically scored as
      grade 1 or higher, which precisely corresponded to the pathological findings. The
      SD-OCT images of EAU were graded as follows: grade 1, a few infiltrating cells in
      the vitreous and retina; grade 2, increased vitreous cells, retinal vasculitis,
      and granulomatous lesion; grade 3, cell infiltration into the whole retina,
      disappearance of IS/OS line, and destruction of the retinal layer structure; and
      grade 4, disappearance of the outer retina. The SD-OCT grade of EAU based on
      these criteria correlated significantly with both the clinical grade (R(2)=0.282,
      p<0.005) and histopathological grade (R(2)=0.846, p<0.0001). CONCLUSIONS: SD-OCT
      is useful for evaluating the development and severity of mouse EAU. The SD-OCT
      scoring system we developed accurately reflects clinical and histopathological
      changes.

PMID- 24574438
TI  - Increased risk of coronary heart disease in male patients with central serous
      chorioretinopathy: results of a population-based cohort study.

PMID- 24574439
TI  - The temperature change in an endotracheal tube during high frequency ventilation
      using an artificial neonatal lung model with Babylog(r) 8000 plus.
AB  - OBJECTIVE: There is little available data on airway humidity during high
      frequency ventilation (HFV). The purpose of this study is to evaluate the
      temperature drop in an endotracheal tube (ETT) during HFV. METHODS: We examined
      the airway temperature in a neonatal HFV system using Babylog(r) 8000 plus. We
      measured the temperature change of inspired gases in the ETT under various
      oscillatory frequencies and oscillatory volumes with a fixed base flow. The
      temperatures in the ETT during HFV were compared with the temperatures during
      conventional intermittent positive pressure ventilation (IPPV). RESULTS: As the
      oscillatory frequency was increased and the oscillatory volume (VThf) decreased,
      the difference in temperature between the Y piece and the inlet of an artificial
      lung in the ETT (ETT outside of body) increased. However, as the oscillatory
      frequency increased, there was no difference in the ETT temperature under
      constant oscillatory volume. In contrast, as the oscillatory volume was
      decreased, the difference in temperature in the ETT was greater under constant
      oscillatory frequency. Moreover, the temperature drop in the ETT with HFV was
      lower than that in the IPPV temperature with a similar respiratory volume.
      CONCLUSIONS: The temperature change in the ETT was not dependent on the
      oscillatory frequency when the oscillatory volume was fixed; however, the
      temperature was dependent on the oscillatory volume when the oscillatory
      frequency was fixed.

PMID- 24574440
TI  - Non-heart transplant surgical approaches with left ventricular restoration and
      mitral valve operation for advanced ischaemic cardiomyopathy.
AB  - OBJECTIVES: The aim of this study was to assess long-term outcomes of non-heart
      transplant surgical approaches to advanced ischaemic cardiomyopathy (ICM),
      including left ventricular restoration (LVR) and mitral valve operation. METHODS:
      Since September 2002, 102 consecutive patients (mean age 65, 18 females) with
      advanced ICM [ejection fraction (EF) <40%, left ventricular end-systolic volume
      index (LVESVI) > 60 ml/m(2)] were treated using non-heart transplant procedures.
      A total of 84 patients with asynergy of large scar exceeding 35% of left
      ventricular (LV) perimeter underwent LVR, and 30 patients with greater than or
      equal to moderate mitral regurgitation (MR) underwent mitral valve operation such
      as annuloplasty (n = 23) and valve replacement (n = 7). Patients were divided
      into four groups according to their interagency registry for mechanically
      assisted circulatory support (INTERMACS) profiles: Profile 1-2 (the highest
      levels of clinical compromise; n = 9), Profile 3-4 (n = 40), Profile 5-6 (n = 32)
      and Profile >= 7 (n = 21). We compared the four groups, looking at survival,
      major adverse cardiac and cerebrovascular event (MACCE), New York Heart
      Association (NYHA) status, LV volume and function. RESULTS: The overall 8-year
      survival including 3 hospital deaths (2.9%) was 64.3% without sudden death due to
      arrhythmia. Ninety-nine survivors showed significant improvement in the mean NYHA
      status, from 2.9 to 1.4, and the mean EF (33.2-41.7%) (P < 0.0001). The mean
      LVESVI was significantly reduced from 104.1 to 61.4 ml/m(2) (41% volume
      reduction) (P < 0.0001). Seven-year survival in patients with Profiles 1-2, 3-4,
      5-6 and >= 7 were 50.0, 57.2, 60.3 and 95.2%, respectively (P = 0.13). Freedom
      from MACCE at 5 years in patients with Profiles 1-2, 3-4, 5-6 and >= 7 were 29.6,
      47.0, 67.2 and 95.2%, respectively (P = 0.0067). The improvements in NYHA status
      were significantly greater in patients with higher levels of clinical compromise
      (P < 0.0001), although, there was no significant difference in LV volume
      reduction and functional improvement among the four groups. Patients with Profile
      >= 7 had significantly better survival at 7 years (hazard ratio (HR): 0.11, P =
      0.046) and freedom from MACCE at 5 years (HR: 0.053, P = 0.0066) compared with
      patients with Profiles 1-2. CONCLUSIONS: Our non-heart transplant surgical
      approaches using LVR and mitral valve operation for advanced ICM yielded
      excellent long-term outcomes in terms of survival and NYHA status, even in
      patients who are potential candidates for heart transplantation or LV assist
      devices; and are encouraging in a very particular situation where heart
      transplantation is limited due to organ storage.

PMID- 24574441
TI  - Transcatheter aortic valve implantation reduces grade of concomitant mitral and
      tricuspid valve regurgitation and pulmonary hypertension.
AB  - OBJECTIVES: The presence of concomitant mitral (MR) or tricuspid regurgitation
      (TR) is a common issue in patients undergoing transcatheter aortic valve
      implantation (TAVI). The objective was (i) to analyse the outcomes of patients
      with concomitant moderate or more severe MR, (ii) to compare the outcomes with
      those of TAVI patients without concomitant MR and (iii) to evaluate the impact of
      TAVI on grade of concomitant MR. METHODS: For creating a homogeneous study group,
      the study was restricted to transapical (TA)-TAVI patients. Since 2008, 615
      patients have undergone TAVI at our institution, 386 of these using the TA
      approach with the Edwards SAPIENTM bioprosthesis. Out of these, 116 (30.1%)
      presented with concomitant moderate or more severe MR. Mean logistic European
      System for Cardiac Operative Risk (EuroSCORE) was 18.1 +/- 11.5%, EuroSCORE II
      5.4 +/- 0.7%. Intra- and post-hospital course, change in grade of MR, TR, right
      ventricular systolic pressure (RVSP) and tricuspid annular plane systolic
      excursion (TAPSE) were particularly analysed. Outcomes were compared with those
      of the remaining TA-TAVI patients (n = 270). Mean follow-up time was 471 +/- 391
      days, giving a total of 135 patient-years. RESULTS: Three patients (2.6%) died
      during primary hospital stay. Estimated 1-, 2-, 3- and 4-year survival rates were
      76.7, 75.6, 68.3 and 50.6% for study and 78.1, 77.8, 61.1 and 55.0% for control
      groups, respectively. Postoperative morbidity and mortality did not differ
      significantly from those of the control group. Postoperatively, a significant
      reduction in MR (2.1 +/- 0.2 to 1.5 +/- 0.7; P < 0.01) and TR (1.9 +/- 0.5 to 1.5
      +/- 0.7; P < 0.01) was observed. Likewise, RVSP decreased significantly from 46
      +/- 16 to 39 +/- 15 mmHg (P < 0.01) and TAPSE non-significantly (21.9 +/- 7.3 to
      19.5 +/- 5.5 mm; P = 0.07). After 3-6 months, 68.9% of the patients were at New
      York Heart Association (NYHA) Class I or II, 25% at Class III and 6.0% downgraded
      to Class IV. A reason for remaining in NYHA Class III or downgrading to NYHA
      Class IV could not be detected, and particularly, there was no impact of grade of
      MR/TR, left ventricular ejection fraction, TAPSE or right ventricular endsystolic
      pressure (RVESP) on outcomes or NYHA class. CONCLUSION: TA-TAVI in patients with
      concomitant moderate or more severe MR provides results comparable with those of
      TA-TAVI in general. Concomitant MR had no significant impact on the short- and
      mid-term outcomes. A significant reduction in MR, TR and pulmonary hypertension
      was observed after TA-TAVI during short-term follow-up. Nonetheless, a relevant
      number of patients did not experience an improvement in NYHA class.

PMID- 24574442
TI  - Conventional or endovascular aortic repair for patients with cardiac and aortic
      pathologies?
AB  - A 62-year-old man with descending aorta aneurysm combined with cardiac
      pathologies was assessed as not suitable for conventional surgery and underwent
      endografting of the thoracoabdominal aorta. Shortly thereafter, he developed
      rapid progression of the aneurysm caused by a proximal leak. The patient
      underwent additional stenting of the left sub-clavian artery without success and
      because the aneurysm reached a diameter of 9.5 cm during the following 4 months
      and vascular surgeons saw no possibility for further reintervention, the patient
      was referred to our clinic to get a second opinion. He underwent successful
      surgery consisting of complete arch replacement with additional covering of the
      descending aorta using the elephant trunk technique as well as ligation and
      bypassing of the left sub-clavian artery. Concomitantly, repair of the mitral and
      tricuspid valves was performed. 

PMID- 24574443
TI  - Non-contiguous spinal tuberculosis with a previous presumptive diagnosis of lung
      cancer spinal metastases.

PMID- 24574444
TI  - Perioperative gabapentin for the prevention of persistent pain after thoracotomy:
      a randomized controlled trial.
AB  - OBJECTIVES: To evaluate the effect of perioperative gabapentin treatment for the
      prevention of persistent post-thoracotomy pain and to establish whether
      gabapentin has a significant therapeutic impact on acute postoperative pain.
      METHODS: Consecutive patients with pulmonary malignancies scheduled for anterior
      thoracotomy were enrolled in this randomized, double-blinded, placebo-controlled
      trial. Patients were given 1200 mg gabapentin or placebo 2 h before surgery
      followed by increasing doses during 5 postoperative days: 600 mg for day 1; 900
      mg for day 2; and 1200 mg for days 3-5. Effective pain relief was provided with
      perioperative multimodal analgesia with epidural infusion of bupivacaine and
      morphine for 72 h, and oral acetaminophen, ibuprofen and morphine. The main
      outcome was persistent post-thoracotomy pain at 6 months. Secondary outcomes
      included measures of early postoperative post-thoracotomy pain, morphine
      requirements, recovery and analgesia-related adverse effects over the first 3
      weeks as well as persistent post-thoracotomy pain at 3 months. RESULTS: A total
      of 104 patients were randomly assigned to the intervention or control group; 86
      (83%) patients were available for the 14-day analysis, 76 (73%) for the 3-month
      analysis and 67 (64%) for the 6-month follow-up. At 6 months postoperatively, 47%
      of patients treated with gabapentin reported persistent post-thoracotomy pain
      compared with 49% in the placebo group (P = 0.9). No overall clinically or
      statistically significant differences were observed between groups receiving
      placebo and gabapentin, respectively, for the secondary outcome measures and
      treatment-related adverse events. CONCLUSIONS: We found no evidence for the
      superiority of gabapentin over placebo for the treatment of acute pain following
      thoracotomy or for the prevention of persistent post-thoracotomy pain.

PMID- 24574445
TI  - Long-term outcomes of the Ross procedure in adults with severe aortic stenosis:
      single-centre experience with 20 years of follow-up.
AB  - OBJECTIVES: The optimal prosthesis option for aortic valve replacement in adult
      patients<60 years of age with severe aortic stenosis (AS) remains controversial.
      The objective was to determine the long-term outcomes of the Ross procedure in
      this population. METHODS: Between 1990 and 2013, 276 patients aged 18 years and
      above (mean 40.3+/-10.6) underwent an elective Ross procedure. Among them, 221
      patients had predominant severe AS; these patients form the study group. The Ross
      procedure was performed either by aortic root replacement (n=190; 86%) or the
      subcoronary technique (n=31; 14%). There were 169 patients with bicuspid valves
      and 33 redo operations including previous aortic valve repair (n=6) and
      replacement (n=9) for severe AS. Demographic, preoperative, postoperative and
      longitudinal clinical and echocardiographic data were collected prospectively.
      The median and mean follow-up were 11.4 years (range: 1-20.1 years) and 10.1+/
      5.9 years, respectively. The follow-up was complete in all patients. Kaplan-Meier
      actuarial survival analysis was performed to assess long-term survival, freedom
      from reoperation for autograft and/or homograft failure and freedom from
      autograft valve insufficiency. Cox regression risk analysis was performed to
      identify factors associated with autograft or homograft reoperations. RESULTS:
      The perioperative mortality rate was 0.9% (n=2). The incidence rate of early
      reoperation for bleeding was 5.9%. The actuarial survival rate at 10 and 15 years
      following surgery was 92.1 and 90.5%, respectively. Ross-related reoperations
      occurred in 21 patients during follow-up: autograft dysfunction (n=9), homograft
      dysfunction (n=6) and both (n=6). The rate of freedom from Ross-related
      reoperation was 94.7 and 87.7% at 10 and 15 years, respectively. The rate of
      freedom from reoperation for autograft failure was 97.6 and 91.5%, the rate of
      freedom from reoperation for homograft failure was 95.7 and 90.8%, and the rate
      of freedom from moderate or severe autograft regurgitation was 94.1 and 85.6% at
      10 and 15 years, respectively. CONCLUSIONS: Compared with available aortic
      bioprosthetic alternatives in young adults with severe AS, the Ross procedure
      provides an excellent long-term option for patients with predominant severe AS
      who seek a durable operation without anticoagulation.

PMID- 24574446
TI  - Quicker yet safe: skeletonization of 1640 internal mammary arteries with harmonic
      technology in 965 patients.
AB  - OBJECTIVES: Skeletonization of the internal mammary artery (IMA) facilitates
      arterial grafting and has been shown to reduce deep sternal infection but is more
      time-consuming and tedious than pedicle harvest. We wished to determine if use of
      harmonic technology (HT) facilitates skeletonization of the IMA and is as safe as
      the conventional technique of skeletonization. METHODS: In a consecutive series
      of 1057 patients with isolated coronary artery bypass graft (CABG) surgery from
      2003 to 2013, adverse events and recorded harvest times were compared between
      harmonic (965 patients) and non-harmonic patients (86 patients). RESULTS: HT was
      used to harvest 1640 IMAs in 965 (91%) of 1057 consecutive CABG patients and
      skeletonization with the traditional technique (use of an electrocautery tip as a
      dissector) was used to harvest 147 IMAs in 86 patients. Six patients had no IMA
      harvested with this surgery (4 patients had an IMA used from a previous CABG, 1
      had no disease of the left anterior descending coronary artery and 1 patient was
      in cardiogenic shock precluding IMA use). Excluding patients with single-vessel
      disease, 730/987 (74%) of patients received bilateral IMAs. Demographics of
      patients with and without harmonic skeletonization, respectively, were the
      following: mean age: 64.7 vs 67.7 years; diabetes: 33 vs 34%; women: 21 vs 26%
      and median European System for Cardiac Operative Risk Evaluation: 2.9 vs 3.2. The
      mean harvest time for 77 non-harmonic skeletonized mammary arteries (49
      surgeries) was 32.2 min (95% confidence interval (CI): 30.1, 34.3), for harmonic
      skeletonized arteries after 450 surgeries was 28.4 min, (95% CI: 27.8, 29.1) and
      in the last 100 IMAs harvested for the isolated harmonic device use/mammary was
      15.4 min (95% CI: 14.0, 16.7). Major adverse events for patients with and without
      harmonic skeletonization, respectively, were: reoperation for bleeding: 2.7 vs
      3.5% (difference = 0.8%, 95% CI: -3.2, 4.8); damaged mammaries: 0.4 vs 0.7%
      (difference = 0.3%, 95% CI: -1.0, 1.7); deep sternal infection: 1.6 vs 1.2%
      (difference = -0.4%, 95% CI: -2.8, 2.0) and perioperative infarction: 1.7 vs 2.3%
      (difference = 0.7%, 95% CI: -2.6, 4.0). CONCLUSION: In this largest series to
      date of harmonic IMA skeletonization, this technique results in rare damage, is
      quicker and with a comparable adverse event rate compared with the non-harmonic
      method.

PMID- 24574447
TI  - Delayed lung herniation after minimally invasive cardiac surgery.

PMID- 24574448
TI  - Acute aortic dissection in an adult patient with retro-oesophageal aortic arch.

PMID- 24574449
TI  - Performance of EuroSCORE II in a large US database: implications for
      transcatheter aortic valve implantation.
AB  - OBJECTIVES: Validation studies of European system for cardiac operative risk
      evaluation II (EuroSCORE II) have been limited to European datasets. Therefore,
      the aims of this study were to assess the performance of EuroSCORE II in a large
      multicentre US database, and compare it with the Society of Thoracic Surgeons
      Predicted Risk of Mortality (STS-PROM). In addition, implications for patient
      selection for transcatheter aortic valve implantation (TAVI) were explored.
      METHODS: EuroSCORE II and the STS-PROM were calculated for 50 588 patients from a
      multi-institutional statewide database of all cardiac surgeries performed since
      2003. Model performance was assessed using the area under the receiver operator
      curve (AUC), observed vs expected (O:E) ratios and calibration plots. Analyses
      were performed for isolated coronary artery bypass grafting (CABG) (n = 40 871),
      aortic valve replacement (AVR) (n = 4107), AVR + CABG (n = 3480), mitral valve
      (MV) replacement (n = 1071) and MV repair (n = 1059). RESULTS: The overall in
      hospital mortality rate was 2.1%. EuroSCORE II was outperformed by the STS-PROM
      in the overall cohort with regard to discrimination (AUC = 0.77 vs 0.81,
      respectively; P < 0.001) and calibration (O:E = 0.68 vs 0.80, respectively).
      Discrimination for CABG was worse with EuroSCORE II (AUC = 0.77 vs STS-PROM:
      0.81, P < 0.001). For other procedures discrimination was similar: AVR (AUC =
      0.71 vs STS-PROM: 0.74, P = 0.40), AVR + CABG (AUC = 0.72 vs STS-PROM: 0.74, P =
      0.47), MV repair (AUC = 0.82 vs STS-PROM: 0.86, P = 0.55) and MV replacement (AUC
      = 0.78 vs STS-PROM: 0.79, P = 0.69). Calibration of EuroSCORE II was worse for
      CABG (O:E = 0.68 vs STS-PROM: 0.80), similar in AVR + CABG (O:E = 0.76 vs STS
      PROM: 0.70) and MV repair (O:E = 0.64 vs STS-PROM: 0.67), while EuroSCORE II may
      be more accurate in AVR (O:E = 0.96 vs STS-PROM: 0.76). Performance of both
      models improved when only recent cases (after 1 January 2008) were used. Ongoing
      TAVI trials aimed at patients with an estimated 4-10% risk of mortality are
      enrolling patients with mean estimated risks of 6.2% (EuroSCORE II) or 6.0% (STS
      PROM), and an actual mortality rate of 4.6% (EuroSCORE II) or 4.8% (STS-PROM).
      CONCLUSIONS: In a large US multicentre database, the STS-PROM performs better
      than EuroSCORE II for CABG. However, EuroSCORE II is a reasonable alternative in
      low-risk CABG patients and in those undergoing other cardiac surgical procedures.
      Clinical trials and physicians that use these scores recruit and treat patients
      who are at a lower risk than anticipated. This potentially leads to overtreatment
      with an investigational device. Decision-making should not solely be based on
      risk scores, but should comprise multidisciplinary heart team discussions.

PMID- 24574450
TI  - Right heart failure and benefits of adjuvant tricuspid valve repair in patients
      undergoing left ventricular assist device implantation.
AB  - OBJECTIVES: Although right heart failure (RVF) is an important issue in the
      management of patients with left ventricular assist devices (LVADs), the benefits
      of performing tricuspid valve repair in conjunction with LVAD implantation have
      not been demonstrated. METHODS: We retrospectively reviewed the records of 141
      patients who received LVAD implantation as a bridge to transplant from May 1999
      to January 2013. We assessed short- and long-term right heart function in 69 of
      these patients who underwent tricuspid valve repair because of moderate-to-severe
      tricuspid regurgitation (TR) or severe dilatation of the tricuspid annulus. RVF
      was defined as the need for a right ventricular assist device or >30 days of
      intravenous inotropic support. TR was graded from 0 to 4, while fibrosis in
      myocardial biopsy samples was graded pathologically from 0 to 3. RESULTS: The
      average duration of LVAD support was 595 days. Twenty-seven patients developed
      RVF and their survival rate was significantly worse than that of patients who did
      not develop RVF (65 vs 91% at 1 year). RVF was significantly related to high
      preoperative ratio of central venous pressure (CVP) to pulmonary capillary wedge
      pressure, high total bilirubin, high fibrosis score and high TR grade. In
      patients who underwent tricuspid valve repair, the TR grade was significantly
      reduced from 2.6 to 1.0, and this decrease was maintained for 2 years. Although
      patients who underwent tricuspid valve repair had significantly higher TR grades,
      ratios of CVP to pulmonary capillary wedge pressure and fibrosis scores
      preoperatively, no survival impairment was seen. CONCLUSIONS: Tricuspid valve
      repair is a useful and durable adjuvant procedure for restoring deteriorated
      right ventricular function in patients requiring LVAD implantation.

PMID- 24574451
TI  - The comparison of complication, pain, quality of life and performance after lung
      resections with thoracoscopy and axillary thoracotomy.
AB  - OBJECTIVES: The aim of this prospective study was to compare the effects of
      axillary thoracotomy (AT) and video-assisted thoracoscopic surgery (VATS) on
      acute-phase responses, pain, performance status and quality of life in patients
      undergoing pulmonary resection. METHODS: Fifty-five patients with peripherally
      located lung lesions were enrolled into this study. Surgery was done by VATS or
      AT. Forced expiratory volume, smoking habits, complications, Charlson comorbidity
      index, sex, age, length of incision, length of operation, length of hospital
      stay, length of drainage, length of air leakage, preoperative and postoperative C
      reactive protein (CRP) values, visual analogue scale, quality of life and
      performance status of the patients were measured and compared. RESULTS: Twenty
      five patients had lung resection with VATS and 30 patients had lung resection
      with AT. The demographic variables were similar. The differences between the two
      groups' postoperative serum CRP levels were significantly lower for the VATS
      group. The length of postoperative stay was significantly shorter for the VATS
      group. There were no other statistical significance between the two groups in
      terms of operative variables, complications, pain, quality of life and
      performance status. CONCLUSIONS: AT is a technique equivalent to VATS in terms of
      early complications, pain, performance status and quality of life; VATS provided
      a shorter postoperative stay.

PMID- 24574452
TI  - Current aspects of extracorporeal membrane oxygenation in a tertiary referral
      centre: determinants of survival at follow-up.
AB  - OBJECTIVES: To describe the clinical results (both early and at follow-up) of
      patients currently receiving extracorporeal membrane oxygenation (ECMO) therapy
      for cardiac and/or pulmonary failure. To assess the effect of indications,
      clinical presentations and ECMO modalities on early/late clinical outcomes. To
      identify baseline factors associated with worse survival at follow-up. METHODS:
      We reviewed the prospectively collected data of 325 patients receiving ECMO
      therapy at a tertiary referral centre during the 2005-2013 period. Follow-up was
      prospectively conducted by dedicated personnel (average: 84 +/- 86 days, 100%
      complete). Survival was analysed by stratified Kaplan-Meier curves. RESULTS: Veno
      arterial (VA) ECMO was employed in 80% of cases (due to early graft failure (EGF)
      in 13% of cases, post-cardiotomy in 29%, primary cardiogenic shock in 42% for
      miscellaneous aetiologies, other indications in 15.4%) and veno-venous (VV) ECMO
      in the remainders (adult respiratory distress syndrome). In the VA and VV groups,
      weaning rates were 59 and 53%, survival at 30th postimplantation day was 44 and
      45% and survival at the end of the follow-up was 41 and 45%, respectively.
      Implantation under advanced life support (ALS) occurred in 15% of cases (26%
      survival at 30 days). VA patients had a higher rate of thrombotic/haemorrhagic
      complications and of transfusion of blood products and shorter ventilation time.
      Worse early and follow-up survival were observed among patients aged >=65 years,
      having pH <= 7, lactates >12 mmol/l, creatinine >200 MUmol/l at implantation or
      receiving ECMO under ALS. No difference in survival was noted among VA vs VV
      patients. Patients receiving ECMO for EGF displayed better early and late
      survival (64% at 30 days and 53% at 6 months) than post-cardiotomy (36 and 34%,
      respectively), post-acute myocardial infarction (48 and 40%) and the remaining
      patients (46 and 45%). CONCLUSIONS: Despite most critical baseline conditions,
      ECMO therapy is confirmed useful for the treatment of patients with acute
      cardiopulmonary failure refractory to conventional treatments. The ECMO modality
      (VA vs VV), as well as indications to support, identifies different patient
      profiles and dissimilar outcomes. Preimplantation markers of gravity and end
      organ damage are useful in the stratification of expected survival. These may
      facilitate clinical decision-making and appropriate allocation of hospital
      resources.

PMID- 24574453
TI  - Giant mycotic pulmonary artery aneurysms in a newborn.

PMID- 24574454
TI  - FAP20 is an inner junction protein of doublet microtubules essential for both the
      planar asymmetrical waveform and stability of flagella in Chlamydomonas.
AB  - The axoneme-the conserved core of eukaryotic cilia and flagella-contains highly
      specialized doublet microtubules (DMTs). A long-standing question is what
      protein(s) compose the junctions between two tubules in DMT. Here we identify a
      highly conserved flagellar-associated protein (FAP), FAP20, as an inner junction
      (IJ) component. The flagella of Chlamydomonas FAP20 mutants have normal length
      but beat with an abnormal symmetrical three-dimensional pattern. In addition, the
      mutant axonemes are liable to disintegrate during beating, implying that
      interdoublet connections may be weakened. Conventional electron microscopy shows
      that the mutant axonemes lack the IJ, and cryo-electron tomography combined with
      a structural labeling method reveals that the labeled FAP20 localizes at the IJ.
      The mutant axonemes also lack doublet-specific beak structures, which are
      localized in the proximal portion of the axoneme and may be involved in planar
      asymmetric flagellar bending. FAP20 itself, however, may not be a beak component,
      because uniform localization of FAP20 along the entire length of all nine DMTs is
      inconsistent with the beak's localization. FAP20 is the first confirmed component
      of the IJ. Our data also suggest that the IJ is important for both stabilizing
      the axoneme and scaffolding intra-B-tubular substructures required for a planar
      asymmetrical waveform. 

PMID- 24574455
TI  - The stoichiometry of the nucleoporin 62 subcomplex of the nuclear pore in
      solution.
AB  - The nuclear pore complex (NPC) regulates transport between the nucleus and
      cytoplasm. Soluble cargo-protein complexes navigate through the pore by binding
      to phenylalanine-glycine (FG)-repeat proteins attached to the channel walls. The
      Nup62 complex contains the FG-repeat proteins Nup62, Nup54, and Nup58 and is
      located in the center of the NPC. The three proteins bind each other via
      conserved coiled-coil segments. To determine the stoichiometry of the Nup62
      complex, we undertook an in vitro study using gel filtration and analytical
      ultracentrifugation. Our results reveal a 1:1:1 stoichiometry of the Nup62
      complex, where Nup54 is central with direct binding to Nup62 and Nup58. At high
      protein concentration, the complex forms larger assemblies while maintaining the
      Nup62:Nup54:Nup58 ratio. For the homologous Nsp1 complex from Saccharomyces
      cerevisiae, we determine the same stoichiometry, indicating evolutionary
      conservation. Furthermore, we observe that eliminating one binding partner can
      result in the formation of complexes with noncanonical stoichiometry, presumably
      because unpaired coiled-coil elements tend to find a promiscuous binding partner.
      We suggest that these noncanonical stoichiometries observed in vitro are unlikely
      to be physiologically relevant. 

PMID- 24574456
TI  - Atmospheric gas plasma-induced ROS production activates TNF-ASK1 pathway for the
      induction of melanoma cancer cell apoptosis.
AB  - Atmospheric gas plasmas (AGPs) are able to selectively induce apoptosis in cancer
      cells, offering a promising alternative to conventional therapies that have
      unwanted side effects such as drug resistance and toxicity. However, the
      mechanism of AGP-induced cancer cell death is unknown. In this study, AGP is
      shown to up-regulate intracellular reactive oxygen species (ROS) levels and
      induce apoptosis in melanoma but not normal melanocyte cells. By screening genes
      involved in apoptosis, we identify tumor necrosis factor (TNF)-family members as
      the most differentially expressed cellular genes upon AGP treatment of melanoma
      cells. TNF receptor 1 (TNFR1) antagonist-neutralizing antibody specifically
      inhibits AGP-induced apoptosis signal, regulating apoptosis signal-regulating
      kinase 1 (ASK1) activity and subsequent ASK1-dependent apoptosis. Treatment of
      cells with intracellular ROS scavenger N-acetyl-l-cysteine also inhibits AGP
      induced activation of ASK1, as well as apoptosis. Moreover, depletion of
      intracellular ASK1 reduces the level of AGP-induced oxidative stress and
      apoptosis. The evidence for TNF-signaling dependence of ASK1-mediated apoptosis
      suggests possible mechanisms for AGP activation and regulation of apoptosis
      signaling pathways in tumor cells. 

PMID- 24574457
TI  - Kinetochore-driven outgrowth of microtubules is a central contributor to
      kinetochore fiber maturation in crane-fly spermatocytes.
AB  - We use liquid crystal polarized light imaging to record the life histories of
      single kinetochore (K-) fibers in living crane-fly spermatocytes, from their
      origins as nascent K-fibers in early prometaphase to their fully matured form at
      metaphase, just before anaphase onset. Increased image brightness due to
      increased retardance reveals where microtubules are added during K-fiber
      formation. Analysis of experimentally generated bipolar spindles with only one
      centrosome, as well as of regular, bicentrosomal spindles, reveals that
      microtubule addition occurs at the kinetochore-proximal ends of K-fibers, and
      added polymer expands poleward, giving rise to the robust K-fibers of metaphase
      cells. These results are not compatible with a model for K-fiber formation in
      which microtubules are added to nascent fibers solely by repetitive "search and
      capture" of centrosomal microtubule plus ends. Our interpretation is that capture
      of centrosomal microtubules-when deployed-is limited to early stages in
      establishment of nascent K-fibers, which then mature through kinetochore-driven
      outgrowth. When kinetochore capture of centrosomal microtubules is not used, the
      polar ends of K-fibers grow outward from their kinetochores and usually converge
      to make a centrosome-free pole. 

PMID- 24574458
TI  - The IL-2/CD25 axis maintains distinct subsets of chronic myeloid leukemia
      initiating cells.
AB  - Just as normal stem cells require niche cells for survival, leukemia-initiating
      cells (LICs) may also require niche cells for their maintenance. Chronic myeloid
      leukemia (CML) is caused by the activity of BCR-ABL, a constitutively active
      tyrosine kinase. CML therapy with tyrosine kinase inhibitors is highly effective;
      however, due to the persistence of residual LICs, it is not curative. Several
      factors are known to support CML LICs, but purification of LICs and a thorough
      understanding of their niche signals have not yet been achieved. Using a CML-like
      mouse model of myeloproliferative disease, we demonstrate that CML LICs can be
      divided into CD25(+)FcepsilonRIalpha(-) Lineage marker (Lin)(-) Sca-1(+)c-Kit(+)
      (F(-)LSK) cells and CD25(-)F(-)LSK cells. The CD25(+)F(-)LSK cells had
      multilineage differentiation capacity, with a preference toward cytokine
      producing mast cell commitment. Although cells interconverted between CD25(-)F(
      )LSK and CD25(+)F(-)LSK status, the CD25(+)F(-)LSK cells exhibited higher LIC
      capacity. Our findings suggest that interleukin-2 derived from the
      microenvironment and CD25 expressed on CML LICs constitute a novel signaling
      axis. The high levels of CD25 expression in the CD34(+)CD38(-) fraction of human
      CML cells indicate that CD25(+) LICs constitute an "LIC-derived niche" that could
      be preferentially targeted in therapy for CML. 

PMID- 24574459
TI  - NOTCH2 and FLT3 gene mis-splicings are common events in patients with acute
      myeloid leukemia (AML): new potential targets in AML.
AB  - Our previous studies revealed an increase in alternative splicing of multiple
      RNAs in cells from patients with acute myeloid leukemia (AML) compared with
      CD34(+) bone marrow cells from normal donors. Aberrantly spliced genes included a
      number of oncogenes, tumor suppressor genes, and genes involved in regulation of
      apoptosis, cell cycle, and cell differentiation. Among the most commonly mis
      spliced genes (>70% of AML patients) were 2, NOTCH2 and FLT3, that encode myeloid
      cell surface proteins. The splice variants of NOTCH2 and FLT3 resulted from
      complete or partial exon skipping and utilization of cryptic splice sites.
      Longitudinal analyses suggested that NOTCH2 and FLT3 aberrant splicing correlated
      with disease status. Correlation analyses between splice variants of these genes
      and clinical features of patients showed an association between NOTCH2-Va splice
      variant and overall survival of patients. Our results suggest that NOTCH2 and
      FLT3 mis-splicing is a common characteristic of AML and has the potential to
      generate transcripts encoding proteins with altered function. Thus, splice
      variants of these genes might provide disease markers and targets for novel
      therapeutics. 

PMID- 24574461
TI  - Introduction to the series of reviews on "Antibody derivatives as new
      therapeutics for hematologic malignancies".

PMID- 24574462
TI  - OK432 versus doxycycline for treatment of macrocystic lymphatic malformations.
AB  - OBJECTIVES: A variety of sclerotherapy agents are used to treat macrocystic
      lymphatic malformations (LMs). This retrospective study at a single institution
      was performed to compare the outcomes of pediatric macrocystic LMs of the head
      and neck that were treated with doxycycline or with OK432. METHODS: The outcomes
      measured included early response to therapy, number of treatments required,
      operating room time, and adverse events. RESULTS: The rates of clinical success
      for OK432 and doxycycline were similar (83% and 82%, respectively; p > 0.05),
      although OK432-treated patients required more treatments than did doxycycline
      treated patients (1.9 versus 1.0 injections; p = 0.01; 95% confidence interval,
      1.57 to 0.27). The average operating room time for a single OK432 injection was
      significantly shorter than that for doxycycline (53.2 versus 98.1 minutes; p <
      0.001); however, when the total number of treatments administered was considered,
      the overall times in the operating room were similar. Adverse events in the early
      postoperative period were more common in OK432-treated patients, who experienced
      marked postoperative swelling compared to doxycycline-treated patients.
      CONCLUSIONS: OK432 and doxycycline are both effective sclerosants for the
      treatment of predominantly macrocystic LMs. The administration time for OK432 is
      shorter than that for doxycycline, but OK432 required more treatments overall to
      achieve clinical success. Early adverse events were more common in OK432-treated
      patients, but longer follow-up is necessary to determine whether rates of
      recurrence and adverse events are similar, particularly in light of the risk of
      tooth discoloration in doxycycline-treated patients.

PMID- 24574460
TI  - SRF is required for neutrophil migration in response to inflammation.
AB  - Serum response factor (SRF) is a ubiquitously expressed transcription factor and
      master regulator of the actin cytoskeleton. We have previously shown that SRF is
      essential for megakaryocyte maturation and platelet formation and function. Here
      we elucidate the role of SRF in neutrophils, the primary defense against
      infections. To study the effect of SRF loss in neutrophils, we crossed Srf(fl/fl)
      mice with select Cre-expressing mice and studied neutrophil function in vitro and
      in vivo. Despite normal neutrophil numbers, neutrophil function is severely
      impaired in Srf knockout (KO) neutrophils. Srf KO neutrophils fail to polymerize
      globular actin to filamentous actin in response to N-formyl-methionine-leucine
      phenylalanine, resulting in significantly disrupted cytoskeletal remodeling. Srf
      KO neutrophils fail to migrate to sites of inflammation in vivo and along
      chemokine gradients in vitro. Polarization in response to cytokine stimuli is
      absent and Srf KO neutrophils show markedly reduced adhesion. Integrins play an
      essential role in cellular adhesion, and although integrin expression levels are
      maintained with loss of SRF, integrin activation and trafficking are disrupted.
      Migration and cellular adhesion are essential for normal cell function, but also
      for malignant processes such as metastasis, underscoring an essential function
      for SRF and its pathway in health and disease. 

PMID- 24574463
TI  - Quality of life after cholesteatoma surgery: intact-canal wall tympanoplasty
      versus canal wall-down tympanoplasty with mastoid obliteration.
AB  - OBJECTIVES: The aim of this study was to evaluate, by means of the Chronic Ear
      Survey (CES), the quality of life of patients who had undergone either intact
      canal wall tympanoplasty (ICWT) or canal wall-down tympanoplasty (CWDT) with
      mastoid obliteration. METHODS: This was a retrospective case review study
      performed at a tertiary referral center. Among 379 patients affected by middle
      ear and mastoid cholesteatoma operated on between November 2000 and December
      2009, 50 patients who underwent ICWT and 50 who underwent CWDT with mastoid
      obliteration were randomly selected. The CES scores were analyzed for both
      groups. RESULTS: The mean scores on the CES were 6.5 +/- 2.1 in patients who
      underwent CWDT and 6.9 +/- 2.2 in patients treated with ICWT (t = -0.93; p >
      0.05). No significant differences between the two groups were found on the
      activity restriction, symptom, or medical resource subscales (p > 0.05).
      CONCLUSIONS: The results of this study demonstrate that CWDT with mastoid
      obliteration resulted in a quality of life comparable with that after ICWT.
      Postoperative hearing loss is the most frequently reported problem for both
      techniques.

PMID- 24574464
TI  - Comparison of survival rates between papillary and follicular thyroid carcinomas
      among 36,725 patients.
AB  - OBJECTIVES: We sought to determine the impact of histologic subtype on disease
      specific survival (DSS) in cases of differentiated thyroid carcinoma. METHODS:
      Adult patients with papillary thyroid carcinoma (PTC) or follicular thyroid
      carcinoma (FTC) were identified from the Surveillance, Epidemiology, and End
      Results (SEER) Database for the years 1988 to 2003. The patients were grouped
      according to tumor type (PTC or FTC), and their age, gender, tumor size and
      extension, and nodal or distant metastases were recorded. The Kaplan-Meier method
      was used to compare DSS rates on the basis of histologic subtype. RESULTS: We
      identified 36,725 patients, of whom 77% were female and 23% were male; PTC was
      diagnosed in 91% of patients, and FTC in the remaining 9%. Patients with PTC were
      younger, were more likely to be female, and had smaller tumors with higher rates
      of regional metastases but fewer distant metastases than FTC patients (p < 0.0001
      for all). When the cases were stratified by stage, FTC patients had a worse DSS
      than did PTC patients for all stages - except for stages III/IVA and IVC among
      patients more than 45 years of age. CONCLUSIONS: Follicular thyroid carcinoma
      portends a worse DSS than does PTC, even when the cases are controlled for stage.
      Consideration should be given to individual staging for these subtypes of
      differentiated thyroid carcinoma.

PMID- 24574465
TI  - Effect of weight loss on short-term outcomes and costs of care after head and
      neck cancer surgery.
AB  - OBJECTIVES: Patients with head and neck cancer (HNC) frequently present with
      weight loss secondary to dysphagia and malnutrition. We sought to determine the
      relationship between weight loss and in-hospital mortality, complications, length
      of hospitalization, and costs in HNC surgery. METHODS: We analyzed discharge data
      from the Nationwide Inpatient Sample for 93,663 patients who underwent an
      ablative procedure for malignant oral cavity, laryngeal, hypopharyngeal, or
      oropharyngeal neoplasms between 2003 and 2008. RESULTS: Weight loss was
      significantly associated with dysphagia (relative risk ratio [RRR] = 3.0; p <
      0.001), alcohol abuse (RRR = 2.0; p < 0.001), advanced comorbidity (RRR = 1.8; p
      < 0.001), Medicaid payor status (RRR = 1.6; p = 0.002), urgent or emergent
      admission (RRR = 1.7; p = 0.015), and major surgical procedures (RRR = 2.3; p <
      0.001). Patients with weight loss had increased risks of acute cardiac events,
      pneumonia, renal failure, sepsis, pulmonary failure (RRR = 2.6; p < 0.001), and
      postoperative wound healing complications, including fistula, dehiscence, and
      surgical site infection (RRR = 2.0; p < 0.001). After we controlled for all other
      variables, weight loss was associated with significantly increased length of
      hospitalization and hospital-related costs. CONCLUSIONS: Weight loss is
      associated with increases in medical complications, surgical complications,
      length of hospitalization, and hospital-related costs in HNC surgical patients.
      Aggressive preoperative identification and treatment of underlying dysphagia and
      malnutrition may reduce the medical and surgical morbidity in this high-risk
      population.

PMID- 24574466
TI  - Endoscopic and three-dimensional radiographic imaging of the pterygopalatine and
      infratemporal fossae: improving surgical landmarks.
AB  - OBJECTIVES: We sought to define the surgical endoscopic anatomy of the
      pterygopalatine fossa (PPF) and infratemporal fossa (ITF) through endoscopic
      cadaver dissections and radiographic imaging analysis. METHODS: Eleven fresh
      cadavers were submitted to computed tomography (CT) and endoscopic dissection. We
      used 3-dimensional (3-D) CT reconstruction and endoscopic video imaging for
      analysis of the bony and soft tissue landmarks. One fixed cadaver head was
      grossly dissected to confirm the endoscopic anatomic findings. RESULTS: The CT
      and 3-D CT reconstruction measurements between the pterygoid canal and the
      foramen rotundum averaged 4.36 mm and 5.09 mm, respectively. An osseous ridge
      (pterygoid ridge) was identified on the anterior face of the pterygoid process as
      a novel identifiable anatomic landmark in all of the specimens. The average
      length of the pterygoid ridge on 3-D CT reconstruction was 7.84 mm. The internal
      maxillary artery entered the PPF posteromedial to the temporalis tendon and
      anterolateral to the lateral pterygoid muscle. The average distance from the
      anterior edge of the lateral pterygoid plate to the foramen ovale was 17.1 mm.
      CONCLUSIONS: The pterygoid ridge is a novel and reliable osseous landmark that
      could assist surgeons during endoscopic surgery on the PPF and ITF. The
      neurovascular and muscular anatomic relationships were characterized for both the
      PPF and the ITF.

PMID- 24574467
TI  - Attendance in voice therapy: can an interdisciplinary care model have an impact?
AB  - OBJECTIVES: We sought to determine the effect of referral patterns on attendance
      in voice therapy. METHODS: Patients who were seen by a laryngologist for vocal
      concerns and referred for voice therapy comprised the study population. Outcomes
      were compared between those who were initially evaluated through the
      interdisciplinary voice clinic (IDC), which combined speech-language pathology
      and laryngology care, and those who were evaluated by a laryngologist alone.
      Adherence was measured by completion of the plan of care. RESULTS: There were 79
      patients evaluated through the IDC and 100 patients evaluated initially by a
      laryngologist. Patients evaluated through the IDC had more visits with the speech
      language pathologist (mean, 3.1 versus 1.24; p < 0.0001). Those initially
      evaluated through the IDC were more likely to complete their plan of care (p =
      0.02). Completion of voice therapy was significantly more likely for individuals
      coded as being of "other" race (odds ratio, 7.98; p = 0.002) and for patients who
      participated in the IDC (odds ratio, 2.56; p = 0.018). The cause of dysphonia,
      sex, marital status, insurance status, days from laryngology referral to the
      initial speech-language pathologist consultation, the initial Voice-Related
      Quality of Life score, and distance to the clinic were not associated with
      patient attendance. CONCLUSIONS: Patients evaluated in a coordinated IDC should
      be more likely to attend voice therapy and complete their plan of care,
      regardless of other factors.

PMID- 24574468
TI  - Stem cell-derived tissue-engineered constructs for hemilaryngeal reconstruction.
AB  - OBJECTIVES: As an initial step toward our goal of developing a completely tissue
      engineered larynx, the aim of this study was to describe and compare three
      strategies of creating tissue-engineered muscle-polymer constructs for
      hemilaryngeal reconstruction. METHODS: Cartilage-mimicking polymer was developed
      from electrospun poly(D,L-lactide-co-epsilon-caprolactone) (PCL). Primary muscle
      progenitor cell cultures were derived from syngeneic F344 rat skeletal muscle
      biopsies. Twenty F344 rats underwent resection of the outer hemilaryngeal
      cartilage with the underlying laryngeal adductor muscle. The defects were
      repaired with muscle stem cell-derived muscle-PCL constructs (5 animals), myotube
      derived muscle-PCL constructs (5 animals), motor end plate-expressing muscle-PCL
      constructs (5 animals), or PCL alone (controls; 5 animals). The outcome measures
      at 1 month included animal survival, muscle thickness, and innervation status as
      determined by electromyography and immunohistochemistry. RESULTS: All of the
      animals survived the 1-month implant period and had appropriate weight gain. The
      group that received motor end plate-expressing muscle-PCL constructs demonstrated
      the greatest muscle thickness and the strongest innervation, according to
      electromyographic activity and the percentage of motor end plates that had nerve
      contact. CONCLUSIONS: Although all of the tissue-engineered constructs provided
      effective reconstruction, those that expressed motor end plates before
      implantation yielded muscle that was more strongly innervated and viable. This
      finding suggests that this novel approach may be useful in the development of a
      tissue-engineered laryngeal replacement.

PMID- 24574469
TI  - Ovine model for auricular reconstruction: porous polyethylene implants.
AB  - OBJECTIVES: We developed a large animal model for auricular reconstruction with
      engineered cartilage frameworks and evaluated the performance of porous
      polyethylene auricular implants in this model. METHODS: Eighteen high-density
      porous polyethylene auricular frameworks were implanted subcutaneously in the
      infra-auricular areas of 9 sheep. The implants were harvested 17 weeks later for
      gross and histologic examination. The perioperative and postoperative courses
      were carefully documented. RESULTS: Five implants became exposed, and 2 implants
      needed to be removed at 7 weeks. Additionally, 1 infected implant was removed at
      2 weeks. Seromas developed in 2 implants because of drain failures and were
      drained successfully during the first postoperative week. There were no other
      surgical site complications. The remaining 10 implants had an acceptable cosmetic
      appearance at 17 weeks. CONCLUSIONS: The perioperative complication rate in the
      ovine porous polyethylene auricular implant model was higher than that reported
      for auricular reconstructions in humans. The implant exposures were likely caused
      by ischemia and excessive stress on the thin overlying skin, because vascularized
      flap coverage was not used. The histologic findings were comparable to the
      results reported for other animal models. This large animal model is appropriate
      for auricular reconstruction experiments, including engineered constructs.

PMID- 24574470
TI  - Results of anterior facial nerve rerouting procedures for removing skull base
      tumors.
AB  - OBJECTIVES: The purpose of this study was to estimate the rates of functional
      recovery of the facial nerve and of total tumor resection in patients who undergo
      short anterior rerouting and long anterior rerouting of the facial nerve in
      removal of skull base tumors. METHODS: We retrospectively collected data on 37
      patients with skull base tumors who underwent facial nerve rerouting during the
      procedure for tumor removal. Information on the rerouting technique, the
      completeness of tumor resection, and changes in facial nerve function were
      obtained from the medical records. Rerouting techniques were classified as short
      anterior rerouting or long anterior rerouting. RESULTS: Ten of 16 patients
      (62.5%) in the group with short anterior rerouting showed postoperative facial
      palsy, and all completely recovered within 1 year. In the group with long
      anterior rerouting, 18 of 21 patients (85.7%) showed postoperative facial palsy,
      and recovery to a preoperative level of facial function was found in 10 patients
      at 1 year of follow-up. Total tumor resection was possible in 94% and 81% of
      patients with short rerouting and long rerouting, respectively. The mean
      operation time was not significantly related to the postoperative recovery of
      facial function. CONCLUSIONS: Short rerouting techniques, when appropriately
      chosen on the basis of tumor and patient characteristics, offer excellent
      preservation of facial function and tumor resection, comparable to those of long
      rerouting techniques.

PMID- 24574471
TI  - MMR vaccination at right time is associated with lower admissions for all
      infections in young children.

PMID- 24574472
TI  - Doctors need training to respond to domestic violence, NICE guidance says.

PMID- 24574473
TI  - Routine testing for women with ovarian cancer.

PMID- 24574475
TI  - Surgery or radiotherapy for prostate cancer?

PMID- 24574474
TI  - Role of quality measurement in inappropriate use of screening for colorectal
      cancer: retrospective cohort study.
AB  - OBJECTIVE: To examine whether the age based quality measure for screening for
      colorectal cancer is associated with overuse of screening in patients aged 70-75
      in poor health and underuse in those aged over age 75 in good health. DESIGN:
      Retrospective cohort study utilizing electronic data from the Veterans Affairs
      (VA) Health Care System, the largest integrated healthcare system in the United
      States. SETTING: VA Health Care System. PARTICIPANTS: Veterans aged >= 50 due for
      repeat average risk colorectal cancer screening at a primary care visit in fiscal
      year 2010. MAIN OUTCOME MEASURES: Completion of colonoscopy, sigmoidoscopy, or
      fecal occult blood testing within 24 months of the 2010 visit. RESULTS: 399,067
      veterans met inclusion/exclusion criteria (mean age 67, 97% men). Of these, 38%
      had electronically documented screening within 24 months. In multivariable log
      binomial regression adjusted for Charlson comorbidity index, sex, and number of
      primary care visits, screening decreased markedly after the age of 75 (the age
      cut off used by the quality measure) (adjusted relative risk 0.35, 95% confidence
      interval 0.30 to 0.40). A veteran who was aged 75 and unhealthy (in whom life
      expectancy might be limited and screening more likely to result in net burden or
      harm) was significantly more likely to undergo screening than a veteran aged 76
      and healthy (unadjusted relative risk 1.64, 1.36 to 1.97). CONCLUSIONS:
      Specification of a quality measure can have important implications for clinical
      care. Future quality measures should focus on individual risk/benefit to ensure
      that patients who are likely to benefit from a service receive it (regardless of
      age), and that those who are likely to incur harm are spared unnecessary and
      costly care.

PMID- 24574476
TI  - From promises to policies: is big pharma delivering on transparency?

PMID- 24574477
TI  - David Owen: researcher into hubris.

PMID- 24574478
TI  - No mission without the marginalized: the scope of family medicine.

PMID- 24574479
TI  - The world's biggest brain.

PMID- 24574480
TI  - Public Health England has "faltering voice" on key issues, say MPs.

PMID- 24574483
TI  - Present and future of folate biofortification of crop plants.
AB  - Improving nutritional health is one of the major socio-economic challenges of the
      21st century, especially with the continuously growing and ageing world
      population. Folate deficiency is an important and underestimated problem of
      micronutrient malnutrition affecting billions of people worldwide. More and more
      countries are adapting policies to fight folate deficiency, mostly by fortifying
      foods with folic acid. However, there is growing concern about this practice,
      calling for alternative or complementary strategies. In addition, fortification
      programmes are often inaccessible to remote and poor populations where folate
      deficiency is most prevalent. Enhancing folate content in staple crops by
      metabolic engineering is a promising, cost-effective strategy to eradicate folate
      malnutrition worldwide. Over the last decade, major progress has been made in
      this field. Nevertheless, engineering strategies have thus far been implemented
      on a handful of plant species only and need to be transferred to highly consumed
      staple crops to maximally reach target populations. Moreover, successful
      engineering strategies appear to be species-dependent, hence the need to adapt
      them in order to biofortify different staple crops with folate. 

PMID- 24574484
TI  - The time of day effects of warm temperature on flowering time involve PIF4 and
      PIF5.
AB  - Warm temperature promotes flowering in Arabidopsis thaliana and this response
      involves multiple signalling pathways. To understand the temporal dynamics of
      temperature perception, tests were carried out to determine if there was a daily
      window of enhanced sensitivity to warm temperature (28  degrees C). Warm
      temperature applied during daytime, night-time, or continuously elicited earlier
      flowering, but the effects of each treatment were unequal. Plants exposed to warm
      night (WN) conditions flowered nearly as early as those in constant warm (CW)
      conditions, while treatment with warm days (WD) caused later flowering than
      either WN or CW. Flowering in each condition relied to varying degrees on the
      activity of CO , FT , PIF4 , and PIF5 , as well as the action of unknown genes.
      The combination of signalling pathways involved in flowering depended on the time
      of the temperature cue. WN treatments caused a significant advance in the
      rhythmic expression waveform of CO, which correlated with pronounced up
      regulation of FT expression, while WD caused limited changes in CO expression and
      no stimulation of FT expression. WN- and WD-induced flowering was partially CO
      independent and, unexpectedly, dependent on PIF4 and PIF5 . pif4-2, pif5-3, and
      pif4-2 pif5-3 mutants had delayed flowering under all three warm conditions. The
      double mutant was also late flowering in control conditions. In addition, WN
      conditions alone imposed selective changes to PIF4 and PIF5 expression. Thus, the
      PIF4 and PIF5 transcription factors promote flowering by at least two means:
      inducing FT expression in WN and acting outside of FT by an unknown mechanism in
      WD. 

PMID- 24574486
TI  - Territorial males can sire more offspring in nests with smaller doors in the
      cichlid Lamprologus lemairii.
AB  - To examine how territorial males counter reproductive parasites, we examined the
      paternity of broods guarded by territorial males using 5 microsatellite loci and
      factors that determine siring success in a wild population of the Lake Tanganyika
      cichlid Lamprologus lemairii. Females enter rock holes (nests) and spawn inside,
      and territorial males release milt over the nest openings. Sneakers attempt to
      dart into the nests, but territorial males often interrupt the attempt. The body
      size of territorial males (territorial defense ability) and the size of nest
      opening (the ability to prevent sneakers from nest intrusions) are predicted to
      be factors that affect paternity at the premating stage, whereas milt quality
      traits are factors that affect paternity at the postmating stage. Parentage
      analyses of 477 offspring revealed that most clutches have few or no cuckolders,
      and territorial males sired >80% of eggs in 7 of the 10 analyzed clutches. Larger
      territorial males that spawned in nests with narrower openings had greater siring
      success. In contrast, none of the milt traits affected the siring success. These
      suggest that territorial male L. lemairii adopt premating strategies whereby they
      effectively prevent reproductive parasitism.

PMID- 24574485
TI  - Expression analysis of Arabidopsis XH/XS-domain proteins indicates overlapping
      and distinct functions for members of this gene family.
AB  - RNA-directed DNA methylation (RdDM) is essential for de novo DNA methylation in
      higher plants, and recent reports established novel elements of this silencing
      pathway in the model organism Arabidopsis thaliana. Involved in de novo DNA
      methylation 2 (IDN2) and the closely related factor of DNA methylation (FDM) are
      members of a plant-specific family of dsRNA-binding proteins characterized by
      conserved XH/XS domains and implicated in the regulation of RdDM at chromatin
      targets. Genetic analyses have suggested redundant as well as non-overlapping
      activities for different members of the gene family. However, detailed insights
      into the function of XH/XS-domain proteins are still elusive. By the generation
      and analysis of higher-order mutant combinations affected in IDN2 and further
      members of the gene family, we have provided additional evidence for their
      redundant activity. Distinct roles for members of the XH/XS-domain gene family
      were indicated by differences in their expression and subcellular localization.
      Fluorescent protein-tagged FDM genes were expressed either in nuclei or in the
      cytoplasm, suggestive of activities of XH/XS-domain proteins in association with
      chromatin as well as outside the nuclear compartment. In addition, we observed
      altered location of a functional FDM1-VENUS reporter from the nucleus into the
      cytoplasm under conditions when availability of further FDM proteins was limited.
      This is suggestive of a mechanism by which redistribution of XH/XS-domain
      proteins could compensate for the loss of closely related proteins.

PMID- 24574487
TI  - Huffman and colleagues' response to Abramson and colleagues' article on statins
      in low risk people.

PMID- 24574488
TI  - Authors' reply to Huffman and colleagues.

PMID- 24574489
TI  - Outbreak of polio-like illness is reported in California.

PMID- 24574490
TI  - Authors' reply to Davis and Dietrich.

PMID- 24574491
TI  - Davis and Dietrich's response to Abramson and colleagues' article on statins in
      low risk people.

PMID- 24574492
TI  - Comparison of the patient-activated event recording system vs. traditional 24 h
      Holter electrocardiography in individuals with paroxysmal palpitations or
      dizziness.
AB  - AIMS: Electrocardiographic documentation of symptomatic episodes of palpitations
      by means of traditional methods such as 24 h Holter monitoring (HM) or loop
      recorders is challenging. Patient-activated electrocardiography (ECG) recorders
      have been proved to be a useful tool in the diagnosis of arrhythmias in these
      patients. However, no comparison studies between the two techniques have been
      conducted. The aim of this study was to compare the diagnostic value of Holter
      ECG and a patient-activated event recorder (OMRON portable HeartScan ECG
      Monitor((r))) (HeartScan) in the detection of arrhythmias in patients with
      paroxysmal palpitations or dizziness suggestive of cardiac arrhythmias. METHODS
      AND RESULTS: Patients with paroxysmal palpitations or dizziness were eligible for
      this study. All patients underwent an HM for 24 h and a 15-day HeartScan after
      the HM. Six hundred and twenty-five patients (48% male, mean age: 37 +/- 11
      years) were included in the study. All patients present with normal heart
      structure, normal baseline 12-lead ECG, and normal echocardiogram. Indications
      for ECG monitoring were palpitations in 577 patients (92.3%) and dizziness in 48
      (7.7%). Holter monitoring offered a clinical diagnosis in 11 patients (1.8%).
      Conversely, HeartScan diagnosed the clinical arrhythmia in 558 individuals (89%).
      Detection of symptoms-related arrhythmias by means of HeartScan was significantly
      higher when compared with HM (P < 0.01). CONCLUSION: The studied system proved to
      be an efficient event recorder providing the diagnosis of the clinical arrhythmia
      in 89% of patients with paroxysmal palpitations or dizziness. Further studies are
      needed to confirm our results.

PMID- 24574493
TI  - A U-shaped association between consumption of marine n-3 fatty acids and
      development of atrial fibrillation/atrial flutter-a Danish cohort study.
AB  - AIMS: Previous studies have suggested a lower risk of atrial fibrillation (AF)
      with higher intakes of fish and marine n-3 polyunsaturated fatty acids (PUFAs),
      but the results have been inconsistent. The aim was to investigate the
      association between consumption of marine n-3 PUFA and development of AF. METHODS
      AND RESULTS: A total of 57 053 Danish participants 50-64 years of age were
      enrolled in the Diet, Cancer, and Health Cohort Study between 1993 and 1997.
      Dietary intake of fish and marine n-3 PUFA was assessed by a semi-quantitative
      food frequency questionnaire. In total, 3345 incident cases of AF occurred over
      13.6 years. Multivariate Cox regression analyses (3284 cases and 55 246
      participants) using cubic splines showed a U-shaped association between
      consumption of marine n-3 PUFA and risk of incident AF, with the lowest risk of
      AF at a moderate intake of 0.63 g/day. For quintiles of marine n-3 PUFA intake, a
      13% statistically significant lower risk of AF was seen in the middle vs. lowest
      quintile: Q1 reference, Q2 HR 0.92 (95% CI 0.82-1.03), Q3 HR 0.87 (95% CI 0.78
      0.98), Q4 HR 0.96 (95% CI 0.86-1.08), and Q5 HR 1.05 (95% CI 0.93-1.18). Intake
      of total fish, fatty fish, and the individual n-3 PUFA eicosapentaenoic acid,
      docosahexaenoic acid, and docosapentaenoic acid also showed U-shaped associations
      with incident AF. CONCLUSION: We found a U-shaped association between consumption
      of marine n-3 PUFA and risk of incident AF, with the lowest risk close to the
      median intake of total marine n-3 PUFA (0.63 g/day).

PMID- 24574494
TI  - Sudden cardiac death: improving our pathological diagnosis--are we there yet?

PMID- 24574495
TI  - Electrical isolation of a substrate after myocardial infarction: a novel ablation
      strategy for unmappable ventricular tachycardias--feasibility and clinical
      outcome.
AB  - AIMS: Catheter ablation can abolish clinical ventricular tachycardia (VT) in
      patients after myocardial infarction (MI). However, VT frequently recurs after
      ablation. The best ablation strategy is still unknown, particularly in patients
      with unmappable VTs. We hypothesized that isolation of the arrhythmogenic
      substrate would be a feasible and effective ablation strategy for the treatment
      of ischaemic VT. METHODS AND RESULTS: Twelve patients (54 +/- 8 years, left
      ventricular ejection fraction, LVEF 32 +/- 13%) underwent catheter ablation for
      sustained VT (anterior MI = 10, inferior MI = 2). All patients had recurrent
      defibrillator shocks, including electrical storms in seven patients, despite anti
      arrhythmic drugs. During electrophysiological study, 3 +/- 2 VTs were induced.
      Three-dimensional mapping of the left ventricle revealed a low-voltage (<1.5 mV)
      area with fractionated electrograms and late potentials, with a mean area of 62
      +/- 20 cm(2). Isolation of the entire low-voltage area was attempted with a
      circumferential line along the low-voltage area border-zone. Substrate isolation
      was successfully achieved in 6 of 12 (50%) patients. Focal discharge within the
      isolated area was demonstrated in three of six (50%) patients. During a median
      follow-up of 479 [297; 781] days, 8 of 12 patients (66.7%) remained free of VT
      recurrence after a single procedure. In five of the six patients (83.3%) with
      successful substrate isolation, there were no VT recurrences when compared with
      three of the six patients (50%) with no substrate isolation. CONCLUSION:
      Electrical isolation of the entire substrate is feasible and appears to be an
      effective treatment in patients with late VT after MI.

PMID- 24574496
TI  - Comparative effectiveness of radical prostatectomy and radiotherapy in prostate
      cancer: observational study of mortality outcomes.
AB  - OBJECTIVE: To compare the survival outcomes of patients treated with surgery or
      radiotherapy for prostate cancer. DESIGN: Observational study. SETTING: Sweden,
      1996-2010. PARTICIPANTS: 34,515 men primarily treated for prostate cancer with
      surgery (n=21,533) or radiotherapy (n=12,982). Patients were categorised by risk
      group (low, intermediate, high, and metastatic), age, and Charlson comorbidity
      score. MAIN OUTCOME MEASURES: Cumulative incidence of mortality from prostate
      cancer and other causes. Competing risks regression hazard ratios for
      radiotherapy versus surgery were computed without adjustment and after propensity
      score and traditional (multivariable) adjustments, as well as after propensity
      score matching. Several sensitivity analyses were performed. RESULTS: Prostate
      cancer mortality became a larger proportion of overall mortality as risk group
      increased for both the surgery and the radiotherapy cohorts. Among patients with
      non-metastatic prostate cancer the adjusted subdistribution hazard ratio for
      prostate cancer mortality favoured surgery (1.76, 95% confidence interval 1.49 to
      2.08, for radiotherapy v prostatectomy), whereas there was no discernible
      difference in treatment effect among men with metastatic disease. Subgroup
      analyses indicated more clear benefits of surgery among younger and fitter men
      with intermediate and high risk disease. Sensitivity analyses confirmed the main
      findings. CONCLUSIONS: This large observational study with follow-up to 15 years
      suggests that for most men with non-metastatic prostate cancer, surgery leads to
      better survival than does radiotherapy. Younger men and those with less
      comorbidity who have intermediate or high risk localised prostate cancer might
      have a greater benefit from surgery.

PMID- 24574497
TI  - Interaction of mesenchymal stem cells with fibroblast-like synoviocytes via
      cadherin-11 promotes angiogenesis by enhanced secretion of placental growth
      factor.
AB  - Bone marrow-derived mesenchymal stem cells (MSC) exist in the synovium of
      patients with rheumatoid arthritis (RA), yet the role of MSC in RA is elusive.
      Placental growth factor (PlGF) expression is increased in RA synovial fluids, and
      blocking of PlGF attenuates progression of arthritis in mice. In this study, we
      observed that PlGF induced chemotaxis of MSC in a dose-dependent manner, which
      was blocked by anti-vascular endothelial growth factor receptor-1 peptide. MSC
      exposed to PlGF elicited increased phosphorylation of Akt and p38 MAPK. PlGF
      mediated chemotaxis was inhibited by PI3K inhibitor (LY294002) and p38 MAPK
      inhibitor (SB203580), but not by ERK1/2 inhibitor (PD98059). Fibroblast-like
      synoviocytes (FLS) constitutively produced PlGF, but MSC released negligible
      amounts of PlGF. Of note, when FLS of RA patients and MSC were cocultured, PlGF
      production by FLS was significantly increased; such an increase was dependent on
      the number of added MSC. Moreover, coculture conditioned medium promoted
      chemotaxis of MSC and increased angiogenesis in Matrigel plugs assay, and these
      were suppressed by preincubation of the medium with anti-PlGF Ab. Transwell
      experiments revealed that MSC to FLS contact was required for the increase in
      PlGF production by coculture. Cadherin-11 was expressed both in FLS and MSC, and
      small interfering RNA knockdown of cadherin-11 in FLS significantly abrogated the
      enhanced PlGF production under coculture conditions. These data indicate that
      increased levels of PlGF in RA joints could induce the migration of MSC to the
      synovium, and interaction of migrated MSC with FLS via cadherin-11 may contribute
      to angiogenesis and chronic synovitis by enhancing the secretion of PlGF. 

PMID- 24574499
TI  - Protective CD4 T cells targeting cryptic epitopes of Mycobacterium tuberculosis
      resist infection-driven terminal differentiation.
AB  - CD4 T cells are crucial to the control of Mycobacterium tuberculosis infection
      and are a key component of current vaccine strategies. Conversely, immune
      mediated pathology drives disease, and recent evidence suggests that adaptive and
      innate responses are evolutionarily beneficial to M. tuberculosis. We compare the
      functionality of CD4 T cell responses mounted against dominant and cryptic
      epitopes of the M. tuberculosis 6-kDa early secreted Ag (ESAT-6) before and
      postinfection. Protective T cells against cryptic epitopes not targeted during
      natural infection were induced by vaccinating mice with a truncated ESAT-6
      protein, lacking the dominant epitope. The ability to generate T cells that
      recognize multiple cryptic epitopes was MHC-haplotype dependent, including
      increased potential via heterologous MHC class II dimers. Before infection,
      cryptic epitope-specific T cells displayed enhanced proliferative capacity and
      delayed cytokine kinetics. After aerosol M. tuberculosis challenge, vaccine
      elicited CD4 T cells expanded and recruited to the lung. In chronic infection,
      dominant epitope-specific T cells developed a terminal differentiated KLRG1(+)/PD
      1(lo) surface phenotype that was significantly reduced in the cryptic epitope
      specific T cell populations. Dominant epitope-specific T cells in vaccinated
      animals developed into IFN-gamma- and IFN-gamma,TNF-alpha-coproducing effector
      cells, characteristic of the endogenous response. In contrast, cryptic epitope
      specific CD4 T cells maintained significantly greater IFN-gamma(+)TNF-alpha(+)IL
      2(+) and TNF-alpha(+)IL-2(+) memory-associated polyfunctionality and enhanced
      proliferative capacity. Vaccine-associated IL-17A production by cryptic CD4 T
      cells was also enhanced, but without increased neutrophilia/pathology. Direct
      comparison of dominant/cryptic epitope-specific CD4 T cells within covaccinated
      mice confirmed the superior ability of protective cryptic epitope-specific T
      cells to resist M. tuberculosis infection-driven T cell differentiation. 

PMID- 24574498
TI  - Long-term B cell depletion in murine lupus eliminates autoantibody-secreting
      cells and is associated with alterations in the kidney plasma cell niche.
AB  - Autoantibodies to dsDNA, produced by autoreactive plasma cells (PCs), are a
      hallmark of systemic lupus erythematosus and play a key role in disease
      pathogenesis. Recent data suggest that autoreactive PCs accumulate not only in
      lymphoid tissues, but also in the inflamed kidney in lupus nephritis. We
      hypothesized that the variable efficacy of anti-CD20 (rituximab)-mediated B cell
      depletion in systemic lupus erythematosus may be related to the absence of an
      effect on autoreactive PCs in the kidney. In this article, we report that an
      enrichment of autoreactive dsDNA Ab-secreting cells (ASCs) in the kidney of lupus
      prone mice (up to 40% of the ASCs) coincided with a progressive increase in
      splenic germinal centers and PCs, and an increase in renal expression for PC
      survival factors (BAFF, a proliferation-inducing ligand, and IL-6) and PC
      attracting chemokines (CXCL12). Short-term treatment with anti-CD20 (4 wk)
      neither decreased anti-dsDNA nor IgG ASCs in different anatomical locations.
      However, long-term treatment (12 wk) significantly reduced both IgG- and dsDNA
      specific ASCs. In addition, long-term treatment substantially decreased splenic
      germinal center and PC generation, and unexpectedly reduced the expression for PC
      survival factors in the kidney. These results suggest that prolonged B cell
      depletion may alter the PC survival niche in the kidney, regulating the
      accumulation and maintenance of autoreactive PCs. 

PMID- 24574500
TI  - Identification of two forms of TNF tolerance in human monocytes: differential
      inhibition of NF-kappaB/AP-1- and PP1-associated signaling.
AB  - The molecular basis of TNF tolerance is poorly understood. In human monocytes we
      detected two forms of TNF refractoriness, as follows: absolute tolerance was
      selective, dose dependently affecting a small group of powerful effector
      molecules; induction tolerance represented a more general phenomenon.
      Preincubation with a high TNF dose induces both absolute and induction tolerance,
      whereas low-dose preincubation predominantly mediates absolute tolerance. In
      cells preincubated with the high TNF dose, we observed blockade of IkappaBalpha
      phosphorylation/proteolysis and nuclear p65 translocation. More prominent in
      cells preincubated with the high dose, reduced basal IkappaBalpha levels were
      found, accompanied by increased IkappaBalpha degradation, suggesting an increased
      IkappaBalpha turnover. In addition, a nuclear elevation of p50 was detected in
      tolerant cells, which was more visible following high-dose preincubation. TNF
      induced phosphorylation of p65-Ser(536), p38, and c-jun was inhibited, and basal
      inhibitory p65-Ser(468) phosphorylation was increased in tolerant cells. TNF
      tolerance induced by the low preincubation dose is mediated by glycogen synthesis
      kinase-3, whereas high-dose preincubation-mediated tolerance is regulated by
      A20/glycogen synthesis kinase-3 and protein phosphatase 1-dependent mechanisms.
      To our knowledge, we present the first genome-wide analysis of TNF tolerance in
      monocytic cells, which differentially inhibits NF-kappaB/AP-1-associated
      signaling and shifts the kinase/phosphatase balance. These forms of
      refractoriness may provide a cellular paradigm for resolution of inflammation and
      may be involved in immune paralysis. 

PMID- 24574502
TI  - A bimodal neurophysiological study of motor control in attention-deficit
      hyperactivity disorder: a step towards core mechanisms?
AB  - Knowledge about the core neural mechanisms of attention-deficit hyperactivity
      disorder, a pathophysiologically heterogeneous psychiatric disorder starting in
      childhood, is still limited. Progress may be achieved by combining different
      methods and levels of investigation. In the present study, we investigated neural
      mechanisms of motor control in 19 children with attention-deficit hyperactivity
      disorder (aged 9-14 years) and 21 age-matched typically developing children by
      relating neural markers of attention and response control (using event-related
      potentials) and measures of motor excitability/inhibition (evoked by transcranial
      magnetic stimulation). Thus, an interplay of processes at a subsecond scale could
      be studied. Using a monetary incentives-based cued Go/No-Go task, parameters that
      are well-known to be reduced in attention-deficit hyperactivity disorder were
      analysed: event-related potential components P3 (following cue stimuli; in Go and
      No-Go trials) and contingent negative variation as well as the transcranial
      magnetic stimulation-based short-interval intracortical inhibition measured at
      different latencies in Go and No-Go trials. For patient and control groups,
      different associations were obtained between performance, event-related potential
      and transcranial magnetic stimulation measures. In children with attention
      deficit hyperactivity disorder, the P3 amplitude in Go trials was not correlated
      with reaction time measures but with short-interval intracortical inhibition at
      rest (r=0.56, P=0.01). In No-Go trials, P3 and short-interval intracortical
      inhibition after inhibiting the response (at 500 ms post-stimulus) were
      correlated in these children only (r=0.62; P=0.008). A classification rate of 90%
      was achieved when using short-interval intracortical inhibition (measured shortly
      before the occurrence of a Go or No-Go stimulus) and the amplitude of the P3 in
      cue trials as input features in a linear discriminant analysis. Findings indicate
      deviant neural implementation of motor control in children with attention-deficit
      hyperactivity disorder reflecting compensatory cognitive mechanisms as a result
      of a basal motor cortical inhibitory deficit (reduced activation of inhibitory
      intracortical interneurons). Both deviant inhibitory and attentional processes,
      which are not related to each other, seem to be characteristic for attention
      deficit hyperactivity disorder at the neural level in motor control tasks. The
      underlying neural mechanisms, which are probably not restricted to the motor
      cortex and the posterior attention network, may play a key role in the
      pathophysiology of this child psychiatric disorder. The high classification rate
      can further be interpreted as a step towards the development of neural markers.
      In summary, the bimodal neurophysiological concept may contribute to developing
      an integrative framework for attention-deficit hyperactivity disorder.

PMID- 24574504
TI  - II. Needle phobia: a psychological perspective.

PMID- 24574501
TI  - Asymmetry and heterogeneity of Alzheimer's and frontotemporal pathology in
      primary progressive aphasia.
AB  - Fifty-eight autopsies of patients with primary progressive aphasia are reported.
      Twenty-three of these were previously described (Mesulam et al., 2008) but had
      their neuropathological diagnoses updated to fit current criteria. Thirty-five of
      the cases are new. Their clinical classification was guided as closely as
      possible by the 2011 consensus guidelines (Gorno-Tempini et al., 2011). Tissue
      diagnoses included Alzheimer's disease in 45% and frontotemporal lobar
      degeneration (FTLD) in the others, with an approximately equal split between TAR
      DNA binding protein 43 proteinopathies and tauopathies. The most common and
      distinctive feature for all pathologies associated with primary progressive
      aphasia was the asymmetric prominence of atrophy, neuronal loss, and disease
      specific proteinopathy in the language-dominant (mostly left) hemisphere. The
      Alzheimer's disease pathology in primary progressive aphasia displayed multiple
      atypical features. Males tended to predominate, the neurofibrillary pathology was
      more intense in the language-dominant hemisphere, the Braak pattern of hippocampo
      entorhinal prominence was tilted in favour of the neocortex, and the APOE e4
      allele was not a risk factor. Mean onset age was under 65 in the FTLD as well as
      Alzheimer's disease groups. The FTLD-TAR DNA binding protein 43 group had the
      youngest onset and fastest progression whereas the Alzheimer's disease and FTLD
      tau groups did not differ from each other in either onset age or progression
      rate. Each cellular pathology type had a preferred but not invariant clinical
      presentation. The most common aphasic manifestation was of the logopenic type for
      Alzheimer pathology and of the agrammatic type for FTLD-tau. The progressive
      supranuclear palsy subtype of FTLD-tau consistently caused prominent speech
      abnormality together with agrammatism whereas FTLD-TAR DNA binding protein 43 of
      type C consistently led to semantic primary progressive aphasia. The presence of
      agrammatism made Alzheimer's disease pathology very unlikely whereas the presence
      of a logopenic aphasia or word comprehension impairment made FTLD-tau unlikely.
      The association of logopenic primary progressive aphasia with Alzheimer's disease
      pathology was much more modest than has been implied by results of in vivo
      amyloid imaging studies. Individual features of the aphasia, such as agrammatism
      and comprehension impairment, were as informative of underlying pathology as more
      laborious subtype diagnoses. At the single patient level, no clinical pattern was
      pathognomonic of a specific neuropathology type, highlighting the critical role
      of biomarkers for diagnosing the underlying disease. During clinical subtyping,
      some patients were unclassifiable by the 2011 guidelines whereas others
      simultaneously fit two subtypes. Revisions of criteria for logopenic primary
      progressive aphasia are proposed to address these challenges. 

PMID- 24574505
TI  - Not fit for a haircut ... how should we assess fitness and stratify risk for
      surgery?

PMID- 24574503
TI  - Ambroxol improves lysosomal biochemistry in glucocerebrosidase mutation-linked
      Parkinson disease cells.
AB  - Gaucher disease is caused by mutations in the glucocerebrosidase gene, which
      encodes the lysosomal hydrolase glucosylceramidase. Patients with Gaucher disease
      and heterozygous glucocerebrosidase mutation carriers are at increased risk of
      developing Parkinson's disease. Indeed, glucocerebrosidase mutations are the most
      frequent risk factor for Parkinson's disease in the general population. Therefore
      there is an urgent need to understand the mechanisms by which glucocerebrosidase
      mutations predispose to neurodegeneration to facilitate development of novel
      treatments. To study this we generated fibroblast lines from skin biopsies of
      five patients with Gaucher disease and six heterozygous glucocerebrosidase
      mutation carriers with and without Parkinson's disease. Glucosylceramidase
      protein and enzyme activity levels were assayed. Oxidative stress was assayed by
      single cell imaging of dihydroethidium. Glucosylceramidase enzyme activity was
      significantly reduced in fibroblasts from patients with Gaucher disease (median
      5% of controls, P = 0.0001) and heterozygous mutation carriers with (median 59%
      of controls, P = 0.001) and without (56% of controls, P = 0.001) Parkinson's
      disease compared with controls. Glucosylceramidase protein levels, assessed by
      western blot, were significantly reduced in fibroblasts from Gaucher disease
      (median glucosylceramidase levels 42% of control, P < 0.001) and heterozygous
      mutation carriers with (median 59% of control, P < 0.001) and without (median 68%
      of control, P < 0.001) Parkinson's disease. Single cell imaging of
      dihydroethidium demonstrated increased production of cytosolic reactive oxygen
      species in fibroblasts from patients with Gaucher disease (dihydroethidium
      oxidation rate increased by a median of 62% compared to controls, P < 0.001) and
      heterozygous mutation carriers with (dihydroethidium oxidation rate increased by
      a median of 68% compared with controls, P < 0.001) and without (dihydroethidium
      oxidation rate increased by a median of 70% compared with controls, P < 0.001)
      Parkinson's disease. We hypothesized that treatment with the molecular chaperone
      ambroxol hydrochloride would improve these biochemical abnormalities. Treatment
      with ambroxol hydrochloride increased glucosylceramidase activity in fibroblasts
      from healthy controls, Gaucher disease and heterozygous glucocerebrosidase
      mutation carriers with and without Parkinson's disease. This was associated with
      a significant reduction in dihydroethidium oxidation rate of ~50% (P < 0.05) in
      fibroblasts from controls, Gaucher disease and heterozygous mutation carriers
      with and without Parkinson's disease. In conclusion, glucocerebrosidase mutations
      are associated with reductions in glucosylceramidase activity and evidence of
      oxidative stress. Ambroxol treatment significantly increases glucosylceramidase
      activity and reduces markers of oxidative stress in cells bearing
      glucocerebrosidase mutations. We propose that ambroxol hydrochloride should be
      further investigated as a potential treatment for Parkinson's disease. 

PMID- 24574506
TI  - From coronary steal to myocardial, renal, and cerebral protection: more questions
      than answers in anaesthetic preconditioning?

PMID- 24574507
TI  - Does circumferential spread of local anaesthetic improve the success of
      peripheral nerve block?
AB  - BACKGROUND: The relation between the pattern of local anaesthetic (LA) spread and
      the quality of peripheral nerve block is unclear. METHODS: Twenty-one volunteers
      were randomized to receive a median nerve block with intended circumferential or
      intended non-circumferential spread of LA. Different predetermined volumes and
      needle placement techniques were used to produce the different patterns of LA
      spread. Volumetric, multiplanar 3D ultrasound imaging was performed to evaluate
      the pattern and extent of LA spread. Sensory block was assessed at predetermined
      intervals. RESULTS: Complete circumferential spread of LA was achieved in only
      67% of cases in the intended circumferential study group and in 33% of cases in
      the intended non-circumferential group. Block success was similar (90%) and
      independent of whether circumferential or non-circumferential spread of the LA
      was achieved. All block failures (n=4) occurred in the intended non
      circumferential group with low volumes of LA. The onset of sensory block
      (independent of group allocation) was faster with circumferential spread of LA
      [median (IQR) onset time, 15 (8; 20) min] compared with non-circumferential
      spread of LA [median (IQR) onset time, 20 (15; 30) min]. More LA was used for
      circumferential blocks [median (IQR) volume of LA 2.8 (1.3; 3.6) vs 1.3 (1.1;
      2.4) ml]. CONCLUSIONS: Even under optimal conditions, it was not possible to
      achieve circumferential spread of LA in all intended cases. The success of median
      nerve block seems to be independent of the pattern of LA spread. CLINICAL TRIAL
      REGISTRATION: DRKS 00003826.

PMID- 24574508
TI  - Association between five lifestyle habits and cancer risk: results from the E3N
      cohort.
AB  - Although some modifiable lifestyle characteristics have been associated with
      decreased cancer risk, little is known about their combined effect or about the
      proportion of cancer cases that could be prevented by improving lifestyle
      behaviors. We aimed to quantify the association between lifestyle habits and all
      site and site-specific cancer risk in middle-aged women. The study included
      64,732 women from the French E3N prospective cohort, ages 43 to 68 years at
      baseline. During a 15-year follow-up period, 6,938 cases of invasive cancer were
      diagnosed. We defined an index that aggregated five lifestyle characteristics:
      smoking, body mass index, alcohol consumption, fruit and vegetable consumption,
      and physical activity. Proportional hazard Cox regressions were performed to
      evaluate the association between lifestyle and cancer risk and to estimate
      multivariate HRs and their 95% confidence intervals (CI). In addition, population
      attributable fractions were used to estimate the proportion of cancer cases that
      could be prevented by healthier behaviors. A significant decrease in all-site
      cancer risk was observed and was associated with a healthy lifestyle (HR, 0.81;
      95% CI, 0.73-0.89 when comparing the highest with the lowest health index
      category; Ptrend across categories < 0.01). Combining all five characteristics
      would have prevented 6.3% (2.2%-10.3%) of any-site, 6.3% (0.5%-12.1%) of
      postmenopausal breast, and 47.5% (26.8%-64.1%) of lung cancers. In conclusion,
      compliance with only five modifiable lifestyle behaviors could prevent a
      significant number of cancers, notably postmenopausal breast and lung cancers.

PMID- 24574509
TI  - Fight or flight and the evolution of pain.

PMID- 24574513
TI  - How a scorpion gets its sting.

PMID- 24574514
TI  - Foxp3+ T cells inhibit antitumor immune memory modulated by mTOR inhibition.
AB  - Inhibition of mTOR signaling enhances antitumor memory lymphocytes. However,
      pharmacologic mTOR inhibition also enhances regulatory T-cell (Treg) activity. To
      counter this effect, Treg control was added to mTOR inhibition in preclinical
      models. Tregs were controlled with CD4-depleting antibodies because CD4 depletion
      has high translational potential and already has a well-established safety
      profile in patients. The antitumor activity of the combination therapy was CD8
      dependent and controlled growth of syngeneic tumors even when an adoptive
      immunotherapy was not used. Lymphocytes resulting from the combination therapy
      could be transferred into naive mice to inhibit aggressive growth of lung
      metastases. The combination therapy enhanced CD8 memory formation as determined
      by memory markers and functional studies of immune recall. Removal of FoxP3
      expressing T lymphocytes was the mechanism underlying immunologic memory
      formation following CD4 depletion. This was confirmed using transgenic DEREG
      (depletion of regulatory T cells) mice to specifically remove Foxp3(+) T cells.
      It was further confirmed with reciprocal studies where stimulation of immunologic
      memory because of CD4 depletion was completely neutralized by adoptively
      transferring tumor-specific Foxp3(+) T cells. Also contributing to tumor control,
      Tregs that eventually recovered following CD4 depletion were less
      immunosuppressive. These results provide a rationale for further study of mTOR
      inhibition and CD4 depletion in patients.

PMID- 24574515
TI  - Six1 promotes epithelial-mesenchymal transition and malignant conversion in human
      papillomavirus type 16-immortalized human keratinocytes.
AB  - Six1, a member of the Six family of homeodomain transcription factors, is
      overexpressed in various human cancers, and SIX1 overexpression is associated
      with tumor progression and metastasis. Six1 messenger RNA levels increase during
      in vitro progression of human papillomavirus type 16 (HPV16)-immortalized human
      keratinocytes (HKc/HPV16) toward a differentiation-resistant (HKc/DR) phenotype.
      In this study, we show that HKc/DR-overexpressing Six1 exhibited a more
      mesenchymal phenotype, as characterized by a fibroblastic appearance and
      increased invasion. We utilized Whole Human Genome Microarrays to explore the
      gene expression changes associated with Six1 overexpression in HKc/DR. We found
      that overexpression of Six1 downregulated epithelial-related genes and
      upregulated mesenchymal-related genes, which suggests that Six1 overexpression
      induces epithelial-mesenchymal transition (EMT). Pathway analysis of the
      microarray data showed alterations in the transforming growth factor-beta (TGF
      beta) pathway, including enhanced expression of the TGF-beta receptor type II
      (TbetaRII), and activation of the mitogen-activated protein kinase (MAPK) pathway
      in HKc/DR-overexpressing Six1, suggesting that Smad-independent pathways of TGF
      beta signaling may be involved in Six1-mediated EMT. p38 MAPK activation was
      required for sustained Six1-induced EMT and TbetaRII overexpression. Finally, we
      determined that Six1 overexpression in HKc/DR resulted in malignant conversion
      and increased the cancer stem cell (CSC)-like population. Thus, Six1
      overexpression promotes EMT, CSCs properties and malignant conversion in HKc/DR
      through MAPK activation, which supports the possible use of p38-TbetaRII
      inhibitors for the treatment of cancers overexpressing Six1.

PMID- 24574516
TI  - Spontaneous reversion of the angiogenic phenotype to a nonangiogenic and dormant
      state in human tumors.
AB  - The angiogenic switch, a rate-limiting step in tumor progression, has already
      occurred by the time most human tumors are detectable. However, despite
      significant study of the mechanisms controlling this switch, the kinetics and
      reversibility of the process have not been explored. The stability of the
      angiogenic phenotype was examined using an established human liposarcoma
      xenograft model. Nonangiogenic cells inoculated into immunocompromised mice
      formed microscopic tumors that remained dormant for approximately 125 days (vs.
      <40 days for angiogenic cells) whereupon the vast majority (>95%) initiated
      angiogenic growth with second-order kinetics. These original, clonally derived
      angiogenic tumor cells were passaged through four in vivo cycles. At each cycle,
      a new set of single-cell clones was established from the most angiogenic clone
      and characterized for in vivo for tumorigenic activity. A total of 132 single
      cell clones were tested in the second, third, and fourth in vivo passage.
      Strikingly, at each passage, a portion of the single-cell clones formed
      microscopic, dormant tumors. Following dormancy, like the original cell line,
      these revertant tumors spontaneously switched to the angiogenic phenotype.
      Finally, revertant clones were transcriptionally profiled and their angiogenic
      output determined. Collectively, these data demonstrate that the angiogenic
      phenotype in tumors is malleable and can spontaneously revert to the
      nonangiogenic phenotype in a population of human tumor cells. IMPLICATIONS:
      Leveraging the rate of reversion to the nonangiogenic phenotype and tumor
      dormancy may be a novel anticancer strategy.

PMID- 24574517
TI  - Androgen receptor promotes the oncogenic function of overexpressed Jagged1 in
      prostate cancer by enhancing cyclin B1 expression via Akt phosphorylation.
AB  - The Jagged1, a Notch signaling pathway ligand, had been shown to have a positive
      correlation with prostate cancer development. Our study for Jagged1 expression in
      218 prostate cancer tissue samples also supports this conclusion. However, the
      detailed molecular mechanism of Jagged1 in promoting the progression of prostate
      cancer is still unclear. Through cell proliferation examination, androgen
      receptor (AR) was found to promote the oncogenic function of Jagged1 to enhance
      the cell proliferation rate by comparing four prostate cancer cell lines, LNCaP,
      LAPC4, DU145, and PC3, which was further validated through analyzing the survival
      of 118 patients treated with androgen-deprivation therapy (ADT) with different
      expression levels of Jagged1 and AR. More importantly, our data showed that
      Jagged1 combined with AR could increase the phosphorylation level of Akt and, in
      turn, phosphorylated Akt plays an important role in regulating the expression
      level of cyclin B1 by interacting with AR and increasing the transcriptional
      activity of AR. These data indicate that prostate cancer progression regulated by
      Jagged1 can be dramatically enhanced by combining with AR through promoting Akt
      activity. IMPLICATIONS: This study could benefit our clinical treatments for
      patients with prostate cancer with overexpressed Jagged1 by targeting AR and Akt.

PMID- 24574518
TI  - DDB2 suppresses tumorigenicity by limiting the cancer stem cell population in
      ovarian cancer.
AB  - Ovarian cancer is an extremely aggressive disease associated with a high
      percentage of tumor recurrence and chemotherapy resistance. Understanding the
      underlying mechanism of tumor relapse is crucial for effective therapy of ovarian
      cancer. DNA damage-binding protein 2 (DDB2) is a DNA repair factor mainly
      involved in nucleotide excision repair. Here, a novel role was identified for
      DDB2 in the tumorigenesis of ovarian cancer cells and the prognosis of patients
      with ovarian cancer. Overexpressing DDB2 in human ovarian cancer cells suppressed
      its capability to recapitulate tumors in athymic nude mice. Mechanistic
      investigation demonstrated that DDB2 is able to reduce the cancer stem cell (CSC)
      population characterized with high aldehyde dehydrogenase activity in ovarian
      cancer cells, probably through disrupting the self-renewal capacity of CSCs. Low
      DDB2 expression correlates with poor outcomes among patients with ovarian cancer,
      as revealed from the analysis of publicly available gene expression array
      datasets. Given the finding that DDB2 protein expression is low in ovarian tumor
      cells, enhancement of DDB2 expression is a promising strategy to eradicate CSCs
      and would help to halt ovarian cancer relapse. IMPLICATIONS: DDB2 status has
      prognostic potential, and elevating its expression eradicates CSCs and could
      reduce ovarian cancer relapse.

PMID- 24574521
TI  - Calcium signaling in plant endosymbiotic organelles: mechanism and role in
      physiology.
AB  - Recent studies have demonstrated that chloroplasts and mitochondria evoke
      specific Ca(2+) signals in response to biotic and abiotic stresses in a stress
      dependent manner. The identification of Ca(2+) transporters and Ca(2+) signaling
      molecules in chloroplasts and mitochondria implies that they play roles in
      controlling not only intra-organellar functions, but also extra-organellar
      processes such as plant immunity and stress responses. It appears that organellar
      Ca(2+) signaling might be more important to plant cell functions than previously
      thought. This review briefly summarizes what is known about the molecular basis
      of Ca(2+) signaling in plant mitochondria and chloroplasts. 

PMID- 24574519
TI  - NEDD9 regulates actin dynamics through cortactin deacetylation in an AURKA/HDAC6
      dependent manner.
AB  - The prometastatic protein NEDD9 (neural precursor cell expressed, developmentally
      downregulated 9) is highly expressed in many cancers and is required for
      mesenchymal individual cell migration and progression to the invasive stage.
      Nevertheless, the molecular mechanisms of NEDD9-driven migration and the
      downstream targets effecting metastasis are not well defined. In the current
      study, knockdown of NEDD9 in highly metastatic tumor cells drastically reduces
      their migratory capacity due to disruption of actin dynamics at the leading edge.
      Specifically, NEDD9 deficiency leads to a decrease in the persistence and
      stability of lamellipodial protrusions similar to knockdown of cortactin (CTTN).
      Mechanistically, it was shown that NEDD9 binds to and regulates acetylation of
      CTTN in an Aurora A kinase (AURKA)/HDAC6-dependent manner. The knockdown of NEDD9
      or AURKA results in an increase in the amount of acetylated CTTN and a decrease
      in the binding of CTTN to F-actin. Overexpression of the deacetylation mimicking
      (9KR) mutant of CTTN is sufficient to restore actin dynamics at the leading edge
      and migration proficiency of the tumor cells. Inhibition of AURKA and HDAC6
      activity by alisertib and Tubastatin A in xenograft models of breast cancer leads
      to a decrease in the number of pulmonary metastases. Collectively, these findings
      identify CTTN as the key downstream component of NEDD9-driven migration and
      metastatic phenotypes. IMPLICATIONS: This study provides a mechanistic platform
      for therapeutic interventions based on AURKA and HDAC6 inhibition for patients
      with metastatic breast cancer to prevent and/or eradicate metastases.

PMID- 24574522
TI  - Rehabilitation of maxillary arch with attachment-retained mesh-reinforced single
      complete denture.
AB  - Fabrication of conventional complete dentures was one of the most commonly
      advised treatment options to mange edentulous patients since many years. One of
      the commonly encountered challenging tasks in prosthodontics is a clinical
      situation in which patients have maxillary completely edentulous arches opposing
      mandibular natural dentition. This situation can be effectively managed by
      retaining some of the natural teeth as overdenture abutments. Tooth supported
      overdenture retained by attachments will improve retention, support and
      stability, and reduces rate of ridge resorption along with psychological benefits
      to the patients by providing tactile sensation. The present case report describes
      management of patients with edentulous maxillary arch opposing natural mandibular
      dentition-rehabilitated attachment-retained mesh-reinforced overdenture. 

PMID- 24574523
TI  - Mechanical mitral valve thrombosis in rheumatic valve disease.

PMID- 24574520
TI  - Autophagy and cancer therapy.
AB  - Autophagy is the process by which cellular material is delivered to lysosomes for
      degradation and recycling. There are three different types of autophagy, but
      macroautophagy, which involves the formation of double membrane vesicles that
      engulf proteins and organelles that fuse with lysosomes, is by far the most
      studied and is thought to have important context-dependent roles in cancer
      development, progression, and treatment. The roles of autophagy in cancer
      treatment are complicated by two important discoveries over the past few years.
      First, most (perhaps all) anticancer drugs, as well as ionizing radiation, affect
      autophagy. In most, but not all cases, these treatments increase autophagy in
      tumor cells. Second, autophagy affects the ability of tumor cells to die after
      drug treatment, but the effect of autophagy may be to promote or inhibit cell
      death, depending on context. Here we discuss recent research related to autophagy
      and cancer therapy with a focus on how these processes may be manipulated to
      improve cancer therapy. 

PMID- 24574524
TI  - Thermal trauma to abdominal wall vascularised composite allotransplant.

PMID- 24574525
TI  - Anabolic steroids abuse-induced cardiomyopathy and ischaemic stroke in a young
      male patient.
AB  - We report a case of a 37-year-old man presented with acute stroke and hepatorenal
      impairment which were associated with anabolic-androgenic steroids (AAS) abuse
      over 2 years. Despite the absence of apparent symptoms and signs of congestive
      heart failure at presentation, an AAS-induced dilated cardiomyopathy with
      multiple thrombi in the left ventricle was attributed to be the underlying cause
      of his condition. Awareness of the complications of AAS led to the prompt
      treatment of the initially unrecognised dilated cardiomyopathy, and improved the
      liver and kidney functions. However, the patient was exposed to a second severe
      ischaemic event, which led to his death. This unique and complex presentation of
      AAS complications opens for better recognition and treatment of their potentially
      fatal effects. 

PMID- 24574526
TI  - DIPNECH presenting on a background of malignant melanoma: new lung nodules are
      not always what they seem.
AB  - The coexistence of lung nodules on a CT scan with worsening respiratory symptoms
      in the context of previous malignant melanoma would usually signify metastatic
      disease. The cause of the lung nodules in this 69-year-old woman turned out to be
      diffuse idiopathic neuroendocrine cell hyperplasia (DIPNECH) with tumourlets.
      DIPNECH is extremely rare, with fewer than 100 cases reported in the literature
      worldwide. The key to making this diagnosis was that the nodules were not avid on
      a positron emission tomography-CT scan, as would have been expected in metastatic
      melanoma. This led to a biopsy diagnosis. At the time of writing, the patient
      remains symptomatic with stable disease. 

PMID- 24574527
TI  - Reversible Top1 cleavage complexes are stabilized strand-specifically at the
      ribosomal replication fork barrier and contribute to ribosomal DNA stability.
AB  - Various topological constraints at the ribosomal DNA (rDNA) locus impose an extra
      challenge for transcription and DNA replication, generating constant torsional
      DNA stress. The topoisomerase Top1 is known to release such torsion by single
      strand nicking and re-ligation in a process involving transient covalent Top1
      cleavage complexes (Top1cc) with the nicked DNA. Here we show that Top1ccs,
      despite their usually transient nature, are specifically targeted to and
      stabilized at the ribosomal replication fork barrier (rRFB) of budding yeast,
      establishing a link with previously reported Top1 controlled nicks. Using
      ectopically engineered rRFBs, we establish that the rRFB sequence itself is
      sufficient for induction of DNA strand-specific and replication-independent
      Top1ccs. These Top1ccs accumulate only in the presence of Fob1 and Tof2, they are
      reversible as they are not subject to repair by Tdp1- or Mus81-dependent
      processes, and their presence correlates with Top1 provided rDNA stability.
      Notably, the targeted formation of these Top1ccs accounts for the previously
      reported broken replication forks at the rRFB. These findings implicate a novel
      and physiologically regulated mode of Top1 action, suggesting a mechanism by
      which Top1 is recruited to the rRFB and stabilized in a reversible Top1cc
      configuration to preserve the integrity of the rDNA. 

PMID- 24574528
TI  - Selective unfolding of one Ribonuclease H domain of HIV reverse transcriptase is
      linked to homodimer formation.
AB  - HIV-1 reverse transcriptase (RT), a critical enzyme of the HIV life cycle and an
      important drug target, undergoes complex and largely uncharacterized
      conformational rearrangements that underlie its asymmetric folding, dimerization
      and subunit-selective ribonuclease H domain (RH) proteolysis. In the present
      article we have used a combination of NMR spectroscopy, small angle X-ray
      scattering and X-ray crystallography to characterize the p51 and p66 monomers and
      the conformational maturation of the p66/p66' homodimer. The p66 monomer exists
      as a loosely structured molecule in which the fingers/palm/connection, thumb and
      RH substructures are connected by flexible (disordered) linking segments. The
      initially observed homodimer is asymmetric and includes two fully folded RH
      domains, while exhibiting other conformational features similar to that of the RT
      heterodimer. The RH' domain of the p66' subunit undergoes selective unfolding
      with time constant ~6.5 h, consistent with destabilization due to residue
      transfer to the polymerase' domain on the p66' subunit. A simultaneous increase
      in the intensity of resonances near the random coil positions is characterized by
      a similar time constant. Consistent with the residue transfer hypothesis, a
      construct of the isolated RH domain lacking the two N-terminal residues is shown
      to exhibit reduced stability. These results demonstrate that RH' unfolding is
      coupled to homodimer formation. 

PMID- 24574536
TI  - Development of neutralizing monoclonal antibodies for oncogenic human
      papillomavirus types 31, 33, 45, 52, and 58.
AB  - Human papillomavirus (HPV) is the etiological agent for all cervical cancers, a
      significant number of other anogenital cancers, and a growing number of head and
      neck cancers. Two licensed vaccines offer protection against the most prevalent
      oncogenic types, 16 and 18, responsible for approximately 70% of cervical cancer
      cases worldwide and one of these also offers protection against types 6 and 11,
      responsible for 90% of genital warts. The vaccines are comprised of recombinantly
      expressed major capsid proteins that self-assemble into virus-like particles
      (VLPs) and prevent infection by eliciting neutralizing antibodies. Adding the
      other frequently identified oncogenic types 31, 33, 45, 52, and 58 to a vaccine
      would increase the coverage against HPV-induced cancers to approximately 90%. We
      describe the generation and characterization of panels of monoclonal antibodies
      to these five additional oncogenic HPV types, and the selection of antibody pairs
      that were high affinity and type specific and recognized conformation-dependent
      neutralizing epitopes. Such characteristics make these antibodies useful tools
      for monitoring the production and potency of a prototype vaccine as well as
      monitoring vaccine-induced immune responses in the clinic. 

PMID- 24574529
TI  - FineSplice, enhanced splice junction detection and quantification: a novel
      pipeline based on the assessment of diverse RNA-Seq alignment solutions.
AB  - Alternative splicing is the main mechanism governing protein diversity. The
      recent developments in RNA-Seq technology have enabled the study of the global
      impact and regulation of this biological process. However, the lack of
      standardized protocols constitutes a major bottleneck in the analysis of
      alternative splicing. This is particularly important for the identification of
      exon-exon junctions, which is a critical step in any analysis workflow. Here we
      performed a systematic benchmarking of alignment tools to dissect the impact of
      design and method on the mapping, detection and quantification of splice
      junctions from multi-exon reads. Accordingly, we devised a novel pipeline based
      on TopHat2 combined with a splice junction detection algorithm, which we have
      named FineSplice. FineSplice allows effective elimination of spurious junction
      hits arising from artefactual alignments, achieving up to 99% precision in both
      real and simulated data sets and yielding superior F1 scores under most tested
      conditions. The proposed strategy conjugates an efficient mapping solution with a
      semi-supervised anomaly detection scheme to filter out false positives and allows
      reliable estimation of expressed junctions from the alignment output. Ultimately
      this provides more accurate information to identify meaningful splicing patterns.
      FineSplice is freely available at https://sourceforge.net/p/finesplice/. 

PMID- 24574537
TI  - Chimeric plantibody passively protects mice against aerosolized ricin challenge.
AB  - Recent incidents in the United States and abroad have heightened concerns about
      the use of ricin toxin as a bioterrorism agent. In this study, we produced, using
      a robust plant-based platform, four chimeric toxin-neutralizing monoclonal
      antibodies that were then evaluated for the ability to passively protect mice
      from a lethal-dose ricin challenge. The most effective antibody, c-PB10, was
      further evaluated in mice as a therapeutic following ricin exposure by injection
      and inhalation.

PMID- 24574538
TI  - Antibodies to the HMW1/HMW2 and Hia adhesins of nontypeable haemophilus
      influenzae mediate broad-based opsonophagocytic killing of homologous and
      heterologous strains.
AB  - The HMW1/HMW2 and Hia proteins are highly immunogenic surface adhesins of
      nontypeable Haemophilus influenzae (NTHi). Approximately 75% of NTHi strains
      express HMW1/HMW2 adhesins, and most of the remaining 25% express an Hia adhesin.
      Our objective in this study was to assess the ability of antisera raised against
      purified HMW1/HMW2 proteins or recombinant Hia proteins to mediate
      opsonophagocytic killing of a large panel of unrelated NTHi strains. Native
      HMW1/HMW2 proteins were purified from three HMW1/HMW2-expressing NTHi strains.
      Recombinant fusion proteins expressing surface-exposed segments of either of two
      prototype Hia proteins were purified from Escherichia coli transformants. Immune
      sera raised in guinea pigs were assessed for their ability to mediate killing of
      NTHi in an opsonophagocytic assay with the HL-60 phagocytic cell line. The three
      HMW1/HMW2 antisera mediated killing of 22 of 65, 43 of 65, and 28 of 65 unrelated
      HMW1/HMW2-expressing NTHi strains, respectively. As a group, the three sera
      mediated killing of 48 of 65 HMW1/HMW2-expressing strains. The two Hia immune
      sera mediated killing of 12 of 24 and 13 of 24 unrelated Hia-expressing NTHi
      strains, respectively. Together, they mediated killing of 15 of 24 Hia-expressing
      strains. Neither the HMW1/HMW2 nor the Hia antisera mediated killing of NTHi
      expressing the alternative adhesin type. Antibodies directed against native
      HMW1/HMW2 proteins and recombinant Hia proteins are capable of mediating broad
      based opsonophagocytic killing of homologous and heterologous NTHi strains. A
      vaccine formulated with a limited number of HMW1/HMW2 and Hia proteins might
      provide protection against disease caused by most NTHi strains.

PMID- 24574539
TI  - Role of antibodies in protection elicited by active vaccination with genetically
      inactivated alpha hemolysin in a mouse model of staphylococcus aureus skin and
      soft tissue infections.
AB  - Due to the emergence of highly virulent community-associated methicillin
      resistant Staphylococcus aureus (CA-MRSA) infections, S. aureus has become a
      major threat to public health. A majority of CA-MRSA skin and soft tissue
      infections in the United States are caused by S. aureus USA300 strains that are
      known to produce high levels of alpha hemolysin (Hla). Therefore, vaccines that
      contain inactivated forms of this toxin are currently being developed. In this
      study, we sought to determine the immune mechanisms of protection for this
      antigen using a vaccine composed of a genetically inactivated form of Hla
      (HlaH35L). Using a murine model of skin and soft tissue infections (SSTI), we
      found that BALB/c mice were protected by vaccination with HlaH35L; however, Jh
      mice, which are deficient in mature B lymphocytes and lack IgM and IgG in their
      serum, were not protected. Passive immunization with anti-HlaH35L antibodies
      conferred protection against bacterial colonization. Moreover, we found a
      positive correlation between the total antibody concentration induced by active
      vaccination and reduced bacterial levels. Animals that developed detectable
      neutralizing antibody titers after active vaccination were significantly
      protected from infection. These data demonstrate that antibodies to Hla represent
      the major mechanism of protection afforded by active vaccination with inactivated
      Hla in this murine model of SSTI, and in this disease model, antibody levels
      correlate with protection. These results provide important information for the
      future development and evaluation of S. aureus vaccines.

PMID- 24574540
TI  - Enzyme-linked immunospot assay for detection of human respiratory syncytial virus
      f protein-specific gamma interferon-producing T cells.
AB  - Respiratory syncytial virus (RSV) causes significant disease in elderly adults,
      and we have previously reported that individuals 65 years of age and older have
      reduced RSV F protein-specific gamma interferon (IFN-gamma)-producing T cells
      compared to healthy younger adults. To measure RSV F-specific memory T cell
      responses in the elderly following infection or vaccination, we optimized and
      qualified an IFN-gamma enzyme-linked immunospot (ELISPOT) assay. Since peripheral
      blood mononuclear cells (PBMC) from the elderly could be more fragile, we
      established optimal cryopreservation techniques and minimal viability acceptance
      criteria. The number of cells per well, types and concentrations of stimulation
      antigens, and incubation times were evaluated to maximize assay sensitivity and
      precision. The optimized assay uses 300,000 cells/well, 2 MUg/ml of an RSV F
      peptide pool (RSV Fpp), and incubation for 22 +/- 2 h in serum-free CTL-Test
      medium. The assay was qualified by 3 analysts using 3 RSV F-responding donor PBMC
      samples (high, medium, and low responders) tested on 5 different assay days. The
      assay sensitivity or limit of detection (LOD) was determined to be 21 spot
      forming cells (SFC) per 10(6) PBMC, and the lower limit of quantitation (LLOQ)
      was estimated to be 63 SFC/10(6) PBMC. The intra- and interassay percent
      coefficients of variation (CV) were <10.5% and <31%, respectively. The results of
      the qualification study demonstrate that a robust, precise, and sensitive IFN
      gamma ELISPOT assay has been developed that is fit for measuring RSV F-specific
      IFN-gamma T cell responses in subjects enrolled in a vaccine clinical trial or in
      epidemiology studies.

PMID- 24574541
TI  - Exaggerated renal fibrosis in P2X4 receptor-deficient mice following unilateral
      ureteric obstruction.
AB  - BACKGROUND: The ATP-sensitive P2X7 receptor (P2X7R) has been shown to contribute
      to renal injury in nephrotoxic nephritis, a rodent model of acute
      glomerulonephritis, and in unilateral ureteric obstruction (UUO), a rodent model
      of chronic interstitial inflammation and fibrosis. Renal tubular cells,
      endothelial cells and macrophages also express the closely related P2X4 receptor
      (P2X4R), which is chromosomally co-located with P2X7R and has 40% homology; it is
      also pro-inflammatory and has been shown to interact with P2X7R to modulate its
      pro-apoptotic and pro-inflammatory effects. Therefore, we chose to explore the
      function of P2X4R in the UUO model of renal injury using knockout mice. We
      hypothesized that UUO-induced tubulointerstitial damage and fibrosis would also
      be attenuated in P2X4R(-/-) mice. METHOD: P2X4R(-/-) and wild-type (WT) mice were
      subjected to either UUO or sham operation. Kidney samples taken on Days 7 and 14
      were evaluated for renal inflammation and fibrosis, and expression of pro
      fibrotic factors. RESULTS: To our surprise, the obstructed kidney in P2X4R(-/-)
      mice showed more severe renal injury, more collagen deposition (picrosirius red
      staining, increase of 53%; P < 0.05) and more type I collagen staining (increase
      of 107%; P < 0.01), as well as increased mRNA for TGF-beta (increase of 102%, P <
      0.0005) and CTGF (increase of 157%; P < 0.05) by Day 14, compared with the UUO WT
      mice. CONCLUSION: These findings showed that lack of P2X4R expression leads to
      increased renal fibrosis, and increased expression of TGF-beta and CTGF in the
      UUO model.

PMID- 24574543
TI  - BK virus infection: an update on diagnosis and treatment.
AB  - BK virus, first isolated in 1971, is a significant risk factor for renal
      transplant dysfunction and allograft loss. Unfortunately, treatment options for
      BK virus infection are limited, and there is no effective prophylaxis. Although
      overimmunosuppression remains the primary risk factor for BK infection after
      transplantation, male gender, older recipient age, prior rejection episodes,
      degree of human leukocyte antigen mismatching, prolonged cold ischemia time, BK
      serostatus and ureteral stent placement have all been implicated as risk factors.
      Routine screening for BK has been shown to be effective in preventing allograft
      loss in patients with BK viruria or viremia. Reduction of immunosuppression
      remains the mainstay of BK nephropathy treatment and is the best studied
      intervention. Laboratory-based methods such as ELISPOT assays have provided new
      insights into the immune response to BK and may help guide therapy in the future.
      In this review, we will discuss the epidemiology of BK virus infection, screening
      strategies, treatment options and future research directions. 

PMID- 24574545
TI  - Lenticulostriate aneurysms: a case series and review of the literature.
AB  - INTRODUCTION: Aneurysms of lenticulostriate artery (LSA) perforators are
      uncommon. There are few data on their natural history, and opinions differ on the
      treatment strategies. OBJECTIVE: We report a case series and summarize the most
      recent literature with current treatment recommendations. We propose an
      anatomical classification for these entities. METHODS: A retrospective review of
      all patients who were diagnosed with an LSA aneurysm on cerebral angiogram was
      performed. An extensive online literature search was performed to identify other
      studies reporting on the diagnosis and management of ruptured and unruptured
      lenticulostriate aneurysms. RESULTS: 48 cases were identified in the literature
      and reviewed: 27 patients were treated surgically; five cases were treated with
      endovascular therapy; two cases underwent gamma knife radiosurgery; and 13 cases
      were managed conservatively. We classified these aneurysms into three types: type
      1 describes aneurysms arising from the middle cerebral artery next to a
      perforating LSA; type 2 is an LSA aneurysm from which the perforating artery or
      arteries arise-the type 2A subtype is one in which the aneurysm neck incorporates
      the origin of the perforating arteries and the type 2B describes perforating
      arteries arising from the dome of the aneurysm; and type 3 describes a fusiform
      aneurysm beyond the first loop or turn of an LSA. CONCLUSIONS: LSA aneurysms are
      rare entities that present several treatment challenges. We have summarized the
      cumulative experience with these lesions and proposed a classification scheme
      that has treatment implications.

PMID- 24574547
TI  - Disorders of consciousness: the changing landscape of treatment.

PMID- 24574542
TI  - Thyroid functional disease: an under-recognized cardiovascular risk factor in
      kidney disease patients.
AB  - Thyroid functional disease, and in particular hypothyroidism, is highly prevalent
      among chronic kidney disease (CKD) and end-stage renal disease (ESRD) patients.
      In the general population, hypothyroidism is associated with impaired cardiac
      contractility, endothelial dysfunction, atherosclerosis and possibly higher
      cardiovascular mortality. It has been hypothesized that hypothyroidism is an
      under-recognized, modifiable risk factor for the enormous burden of
      cardiovascular disease and death in CKD and ESRD, but this has been difficult to
      test due to the challenge of accurate thyroid functional assessment in uremia.
      Low thyroid hormone levels (i.e. triiodothyronine) have been associated with
      adverse cardiovascular sequelae in CKD and ESRD patients, but these metrics are
      confounded by malnutrition, inflammation and comorbid states, and hence may
      signify nonthyroidal illness (i.e. thyroid functional test derangements
      associated with underlying ill health in the absence of thyroid pathology).
      Thyrotropin is considered a sensitive and specific thyroid function measure that
      may more accurately classify hypothyroidism, but few studies have examined the
      clinical significance of thyrotropin-defined hypothyroidism in CKD and ESRD. Of
      even greater uncertainty are the risks and benefits of thyroid hormone
      replacement, which bear a narrow therapeutic-to-toxic window and are frequently
      prescribed to CKD and ESRD patients. In this review, we discuss mechanisms by
      which hypothyroidism adversely affects cardiovascular health; examine the
      prognostic implications of hypothyroidism, thyroid hormone alterations and
      exogenous thyroid hormone replacement in CKD and ESRD; and identify areas of
      uncertainty related to the interplay between hypothyroidism, cardiovascular
      disease and kidney disease requiring further investigation. 

PMID- 24574546
TI  - A Kir3.4 mutation causes Andersen-Tawil syndrome by an inhibitory effect on
      Kir2.1.
AB  - OBJECTIVE: To identify other causative genes for Andersen-Tawil syndrome, which
      is characterized by a triad of periodic paralysis, cardiac arrhythmia, and
      dysmorphic features. Andersen-Tawil syndrome is caused in a majority of cases by
      mutations in KCNJ2, which encodes the Kir2.1 subunit of the inwardly rectifying
      potassium channel. METHODS: The proband exhibited episodic flaccid weakness and a
      characteristic TU-wave pattern, both suggestive of Andersen-Tawil syndrome, but
      did not harbor KCNJ2 mutations. We performed exome capture resequencing by
      restricting the analysis to genes that encode ion channels/associated proteins.
      The expression of gene products in heart and skeletal muscle tissues was examined
      by immunoblotting. The functional consequences of the mutation were investigated
      using a heterologous expression system in Xenopus oocytes, focusing on the
      interaction with the Kir2.1 subunit. RESULTS: We identified a mutation in the
      KCNJ5 gene, which encodes the G-protein-activated inwardly rectifying potassium
      channel 4 (Kir3.4). Immunoblotting demonstrated significant expression of the
      Kir3.4 protein in human heart and skeletal muscles. The coexpression of Kir2.1
      and mutant Kir3.4 in Xenopus oocytes reduced the inwardly rectifying current
      significantly compared with that observed in the presence of wild-type Kir3.4.
      CONCLUSIONS: We propose that KCNJ5 is a second gene causing Andersen-Tawil
      syndrome. The inhibitory effects of mutant Kir3.4 on inwardly rectifying
      potassium channels may account for the clinical presentation in both skeletal and
      heart muscles.

PMID- 24574548
TI  - Logopenic, mixed, or Alzheimer-related aphasia?
AB  - OBJECTIVE: This study tested the hypothesis that patients with primary
      progressive aphasia (PPA) who do not meet the proposed criteria for any of the
      recognized subtypes would have the atrophy pattern reported in the past for
      logopenic variant PPA (lvPPA), in turn suggesting that the PPA of likely
      Alzheimer disease origin is more variable than that captured in the current lvPPA
      diagnostic recommendations. METHODS: MRI gray matter volumes from 14 patients
      with mixed PPA who failed to meet the diagnostic recommendations for any
      recognized variant were compared with those of 25 matched control participants
      via voxel-based morphometry. RESULTS: The mixed PPA group had left
      temporoparietal atrophy with a pattern identical to that in previously reported
      lvPPA cohorts. CONCLUSION: Patients with PPA who did not meet the criteria for
      any recognized PPA variant at their initial assessment had the group-level
      atrophy pattern previously reported as the hallmark of lvPPA. We suggest that the
      specific language features proposed for lvPPA are too narrow to characterize the
      language impairments arising from likely Alzheimer pathology.

PMID- 24574544
TI  - Elevated high-density lipoprotein cholesterol and cardiovascular mortality in
      maintenance hemodialysis patients.
AB  - BACKGROUND: High-density lipoprotein (HDL) confers protection against
      atherosclerosis by several different mechanisms. Although in the general
      population, increasing levels of HDL are associated with reduced cardiovascular
      (CV) mortality, this association is not well known in patients with chronic
      disease states such as end-stage renal disease. We hypothesize that the
      association of serum HDL concentration and its ratio to total cholesterol with
      all-cause and CV mortality in hemodialysis patients is different from the general
      population. METHODS: A 3-year (July 2004 to June 2007) cohort of 33 109 chronic
      hemodialysis patients was studied in the USA in the dialysis clinics where lipid
      profile was measured in at least 50% of all outpatients of the clinic during a
      given calendar quarter. Cox proportional hazard models were adjusted for
      demographics and case-mix variables and cubic splines were plotted. RESULTS:
      Higher HDL concentrations up to 50 mg/dL were associated with better overall
      survival, while HDL at 60 mg/dL and above was associated with a rise in all-cause
      and CV mortality. All-cause and CV mortality hazard ratio was 1.28 (1.20-1.38)
      and 1.08 (1.01-1.16) for HDL <30 mg/dL and 1.05 (1.00-1.10) and 1.08 (1.00-1.16)
      for HDL >= 60 mg/dL, respectively (reference: HDL: 30-<60 mg/dL). CONCLUSIONS: In
      contrast to the general population, low total cholesterol to HDL ratio was
      associated with higher mortality in hemodialysis patients. A U-shaped association
      between HDL cholesterol level and all-cause and CV mortality exists in
      hemodialysis patients with HDL between 50 and <60 mg/dL exhibiting the best
      survival. The underlying mechanisms responsible for these seemingly paradoxical
      associations await further investigation.

PMID- 24574551
TI  - The reversal on Gay Rights in India.

PMID- 24574549
TI  - tDCS in patients with disorders of consciousness: sham-controlled randomized
      double-blind study.
AB  - OBJECTIVE: We assessed the effects of left dorsolateral prefrontal cortex
      transcranial direct current stimulation (DLPF-tDCS) on Coma Recovery Scale
      Revised (CRS-R) scores in severely brain-damaged patients with disorders of
      consciousness. METHODS: In a double-blind sham-controlled crossover design,
      anodal and sham tDCS were delivered in randomized order over the left DLPF cortex
      for 20 minutes in patients in a vegetative state/unresponsive wakefulness
      syndrome (VS/UWS) or in a minimally conscious state (MCS) assessed at least 1
      week after acute traumatic or nontraumatic insult. Clinical assessments were
      performed using the CRS-R directly before and after anodal and sham tDCS
      stimulation. Follow-up outcome data were acquired 12 months after inclusion using
      the Glasgow Outcome Scale-Extended. RESULTS: Patients in MCS (n = 30; interval 43
      +/- 63 mo; 19 traumatic, 11 nontraumatic) showed a significant treatment effect
      (p = 0.003) as measured by CRS-R total scores. In patients with VS/UWS (n = 25;
      interval 24 +/- 48 mo; 6 traumatic, 19 nontraumatic), no treatment effect was
      observed (p = 0.952). Thirteen (43%) patients in MCS and 2 (8%) patients in
      VS/UWS further showed postanodal tDCS-related signs of consciousness, which were
      observed neither during the pre-tDCS evaluation nor during the pre- or post-sham
      evaluation (i.e., tDCS responders). Outcome did not differ between tDCS
      responders and nonresponders. CONCLUSION: tDCS over left DLPF cortex may
      transiently improve signs of consciousness in MCS following severe brain damage
      as measured by changes in CRS-R total scores. CLASSIFICATION OF EVIDENCE: This
      study provides Class II evidence that short-duration tDCS of the left DLPF cortex
      transiently improves consciousness as measured by CRS-R assessment in patients
      with MCS.

PMID- 24574552
TI  - The mental health care bill 2013: A disaster in the offing?

PMID- 24574554
TI  - Role of nicotine receptor partial agonists in tobacco cessation.
AB  - One in three adults in India uses tobacco, a highly addictive substance in one or
      other form. In addition to prevention of tobacco use, offering evidence-based
      cessation services to dependent tobacco users constitutes an important approach
      in addressing this serious public health problem. A combination of behavioral
      methods and pharmacotherapy has shown the most optimal results in tobacco
      dependence treatment. Among currently available pharmacological agents, drugs
      that preferentially act on the alpha4 beta2-nicotinic acetyl choline receptor
      like varenicline and cytisine appear to have relatively better cessation
      outcomes. These drugs are in general well tolerated and have minimal drug
      interactions. The odds of quitting tobacco use are at the very least doubled with
      the use of partial agonists compared with placebo and the outcomes are also
      superior when compared to nicotine replacement therapy and bupropion. The poor
      availability of partial agonists and specifically the cost of varenicline, as
      well as the lack of safety data for cytisine has limited their use world over,
      particularly in developing countries. Evidence for the benefit of partial
      agonists is more robust for smoking rather than smokeless forms of tobacco.
      Although more studies are needed to demonstrate their effectiveness in different
      populations of tobacco users, present literature supports the use of partial
      agonists in addition to behavioral methods for optimal outcome in tobacco
      dependence. 

PMID- 24574555
TI  - Physician's practices and perspectives regarding tobacco cessation in a teaching
      hospital in Mysore City, Karnataka.
AB  - CONTEXT: Tobacco is a leading cause of disease and premature death. Most of the
      smokers visit a doctor for various health related ailments and thus such clinic
      visits provide many opportunities for interventions and professional tobacco
      cessation advice. AIMS: The primary aim of the following study is to assess the
      physician practices, perspectives, resources, barriers and education relating to
      tobacco cessation and their perceived need for training for the same. The
      secondary aim is to compare the physician's cessation practices from patient's
      perspective. SETTINGS AND DESIGN: A descriptive study was conducted in a hospital
      attached to Medical College in Mysore city, Karnataka. MATERIALS AND METHODS:
      Information about doctor's practices, perspectives and their perceived need for
      training in tobacco cessation were collected using pre-structured self
      administered Questionnaire, which were distributed in person. Patient's practices
      and perspectives were assessed using a pre-structured Oral Questionnaire.
      RESULTS: Almost 95% of physicians said that they ask patients about their smoking
      status and 94% advise them to quit smoking, but only 50% assist the patient to
      quit smoking and only 28% arrange follow-up visits. Thus, they do not regularly
      provide assistance to help patients quit, even though 98% of the physicians
      believed that helping patients to quit was a part of their role. Only 18% and 35%
      of the physicians said that Undergraduate Medical Education and Post Graduate
      Medical Education respectively prepared them very well to participate in smoking
      cessation activities. CONCLUSIONS: Tobacco cessation requires repeated and
      regular assistance. Such assistance is not being provided to patients by
      attending doctors. Our medical education system is failing to impart the
      necessary skills to doctors, needed to help patients quit smoking. Reforms in
      education are needed so as to prepare the physician to effectively address this
      problem.

PMID- 24574553
TI  - Cannabis and psychosis: Neurobiology.
AB  - Cannabis is a known risk factor for schizophrenia, although the exact
      neurobiological process through which the effects on psychosis occur is not well
      understood. In this review, we attempt to develop and discuss a possible pathway
      for the development of psychosis. We examine the neurobiological changes due to
      cannabis to see if these changes are similar to those seen in schizophrenic
      patients the findings show similarities; however, these mere similarities cannot
      establish a 'cause-effect' relationship as a number of people with similar
      changes do not develop schizophrenia. Therefore, the 'transition-to-psychosis'
      due to cannabis, despite being a strong risk factor, remains uncertain based upon
      neurobiological changes. It appears that other multiple factors might be involved
      in these processes which are beyond neurobiological factors. Major advances have
      been made in understanding the underpinning of marijuana dependence, and the role
      of the cannabinoid system, which is a major area for targeting medications to
      treat marijuana withdrawal and dependence, as well as other addictions is of now,
      it is clear that some of the similarities in the neurobiology of cannabis and
      schizophrenia may indicate a mechanism for the development of psychosis, but its
      trajectories are undetermined. 

PMID- 24574557
TI  - Behavioral management in children with intellectual disabilities in a resource
      poor setting in Barwani, India.
AB  - BACKGROUND: Management of behavioral problems in children with intellectual
      disabilities (ID) is a great concern in resource-poor areas in India. This study
      attempted to analyze the efficacy of behavioral intervention provided in resource
      poor settings. OBJECTIVE: This study was aimed to examine the outcome of
      behavioral management provided to children with ID in a poor rural region in
      India. MATERIALS AND METHODS: We analyzed data from 104 children between 3 and 18
      years old who received interventions for behavioral problems in a clinical or a
      community setting. The behavioral assessment scale for Indian children with
      mental retardation (BASIC-MR) was used to quantify the study subjects' behavioral
      problems before and after we applied behavioral management techniques (baseline
      and post-intervention, respectively). The baseline and post-intervention scores
      were analyzed using the following statistical techniques: Wilcoxon matched-pairs
      signed-rank test for the efficacy of intervention; chi(2) for group differences.
      RESULTS: The study demonstrated behavioral improvements across all behavior
      domains (P < 0.05). Levels of improvement varied for children with different
      severities of ID (P = 0.001), between children who did and did not have multiple
      disabilities (P = 0.011). CONCLUSION: The outcome of this behavioral management
      study suggests that behavioral intervention can be effectively provided to
      children with ID in poor areas.

PMID- 24574556
TI  - A systematic review and meta-analysis of trials of treatment of depression from
      India.
AB  - BACKGROUND: Antidepressants hold the center stage in the treatment of depression
      in current clinical practice. However, it is also well-known that the treatment
      response and dosage requirement are influenced by ethnic variations. Although
      many efficacy studies have evaluated the efficacy of antidepressants, there is
      lack of systematic reviews and meta-analysis of the existing literature from
      India. OBJECTIVE: To systematically review the efficacy of treatment of
      depression in the Indian context. MATERIALS AND METHODS: We searched PubMed,
      Psychinfo, Medknow and Google scholar to identify studies published in peer
      reviewed English language journals. All controlled trials from India evaluating
      the clinical efficacy of antidepressants, electroconvulsive therapy (ECT), and
      repetitive transcranial magnetic stimulation (rTMS) for management of depression
      were evaluated. Data were extracted using standard procedures and risk of bias
      was evaluated. Effect sizes were computed for the individual studies. RESULTS:
      Effect sizes were computed from 35 clinical trials. Overall, medications were
      superior to placebo for treatment of depression (mean effect size (ES) of 0.87,
      confidence intervals (CI of 0.71-1.02). The effect was greatest for tricyclic
      antidepressants (ES of 1.00, CI of 0.80-1.21) followed by monoamine oxidase
      inhibitors (ES 0.54, CI of 0.40-0.67). ECT was superior to antidepressants (ES
      0.32, CI of - 0.21 to 0.86) and active rTMS was found to be superior to sham rTMS
      with mean effect size of 0.74 (CI 0.39-1.08). Risk of bias was found to be
      considerable. However, the review literature suggests that most of the studies
      have not been powered adequately and have been limited to small sample sizes.
      CONCLUSIONS: Although there is some data from India with respect to efficacy of
      antidepressants, most of the trials have been of shorter duration have been
      inadequately powered. The available data support the superiority of
      antidepressants over placebo and that of ECT over antidepressants.

PMID- 24574559
TI  - Factors influencing access to psychiatric treatment in persons with
      schizophrenia: A qualitative study in a rural community.
AB  - PURPOSE: In low and middle-income countries, about 80% of those who need mental
      health services do not receive them. Reasons for this have not been
      systematically studied. In this qualitative study, we explored this issue in a
      rural community of South India among schizophrenia patients. MATERIALS AND
      METHODS: Patients who had never sought psychiatric treatment despite long
      standing psychotic illnesses were identified as part of a community intervention
      program. In-depth interviews were conducted with patients' caregivers to
      understand factors preventing them seeking psychiatric treatment. Interviews were
      audio-recorded and transcribed. Reasons cited by family members were listed and
      grouped into factors based on themes. Interview process was iteratively followed
      till no new factor emerged. Sixteen caregivers were thus interviewed. RESULTS:
      Content analysis brought out 75 reasons, which were further grouped under the
      following 15 factors [n (%)]: Lack of awareness about the illness: 15 (93.75%);
      lack of family support: Nine (56.25%); religious attributions: Nine (56.25%);
      financial constraints: Six (37.5%); family dynamics: Seven (43.75%); family's
      tolerance: Seven (43.75%); lack of insight: Five (31.25%); families resilience:
      Four (25.0%); community beliefs regarding mental illnesses: Four (25%), and
      others. In each patient, a complex interplay of several of these factors
      precluded the family from seeking psychiatric treatment. CONCLUSIONS: In addition
      to the well-known factors, many hitherto less-understood factors (e.g., families'
      conflicts, dynamics, resilience and acceptance, and community support, etc.) were
      identified which prevented patients and their families from seeking treatment.
      These findings have important policy implications.

PMID- 24574558
TI  - Plasma homocysteine levels in depression and schizophrenia in South Indian
      Tamilian population.
AB  - CONTEXT: Hyperhomocysteinemia has been associated with psychiatric diseases in
      non-Indian populations. OBJECTIVES: We aimed to determine if total plasma
      Homocysteine (Hcys) is associated with schizophrenia or depression in South
      Indian Tamil patients and if so, to correlate their severity and phenomenology to
      Hcys levels. SETTINGS AND DESIGN: 40 patients each with schizophrenia and
      depression and 40 healthy controls were recruited from the psychiatry department
      of a quaternary referral centre. Association between Hcys and psychiatric
      disorders was determined using a Case- control design. Hcys levels were
      correlated with age, gender and severity and duration of the disease by
      appropriate statistical methods using SPSS17. MATERIALS AND METHODS:
      Schizophrenia and depression were defined using ICD10 DCR version. Severity of
      depression was assessed by Hamilton Depression Rating Scale and that of
      schizophrenia using Positive and Negative Schizophrenia scales (PANSS). Hcys
      levels were determined using automated chemiluminiscence immunoassay (74-76).
      STATISTICAL ANALYSIS: Differences between the mean values of plasma homocysteine
      levels among schizophrenia, depression and control groups were compared using
      analysis of variants. The association between the severity and duration of
      schizophrenia and depression and the plasma homocysteine levels were determine
      using Pearson correlation. CONCLUSIONS: In Tamilian population, schizophrenia and
      depression are associated with total plasma Hcys levels which correlated with the
      duration and severity of psychosis.

PMID- 24574560
TI  - Absent posterior alpha rhythm: An indirect indicator of seizure disorder?
AB  - HYPOTHESIS: Absence of normal posterior alpha rhythm is an indirect indicator of
      seizure disorder. MATERIALS AND METHODS: Study group consists of 116 child and
      adolescent patients in the age range of 5-17 years, with established history of
      seizure disorder. Follow-up cases of seizure disorder formed first comparison
      group, patients with a history of pseudo-seizures formed second comparison group
      and patients with a history of headache formed the third comparison group.
      RESULTS: In significant 48.3% (56) patients within the study group there was no
      visible alpha rhythm. Whereas, this absent alpha rhythm criteria was seen in only
      11.2% (4) patients in first and 15% (8) patients in second and in only 6.1% (2)
      patients in third comparison groups. DISCUSSION: Absent alpha rhythm- a criterion
      seems to have a certain amount of specificity for electroencephalograms (EEGs)
      with seizure disorder patients. Presence of seizure activity and absence of alpha
      activity in EEG significantly correlated to each other (Significant at < 0.01
      level). Absent alpha rhythm appears to be a state marker rather than a trait
      marker of seizure disorder.

PMID- 24574561
TI  - Development of the caregivers attitude scale on home care of schizophrenics
      (CASHS).
AB  - BACKGROUND: Schizophrenia is a severe mental disorder that elicits feelings of
      strangeness and discomfort, which may create stigma and lead to the social
      exclusion of the mentally ill and of the people relating with them. In the past
      decade, there has been an increase in the number of research studies on attitudes
      toward mental disorders. MATERIALS AND METHODS: An instrument was developed to
      assess the attitude of primary caregivers on home care of schizophrenics. This
      article describes the development of a Likert scale, the Caregivers Attitude
      Scale on Home Care of Schizophrenics CASHS, which is a 31-item self-reported
      instrument that quantifies three aspects of home care, that is, attitude towards
      patient, towards treatment, and towards social interaction. The steps involved in
      its development are the review of literature, development of items, content
      validation, translation and language validity, pretesting, and reliability.
      RESULTS: After establishing the content validity, the CASHS was pretested with
      five subjects. To establish the reliability of the CASHS, 21 primary caregivers
      were recruited through purposive sampling technique. In order to measure the
      stability between scores obtained, a test-retest reliability was computed using
      Karl Pearson correlation coefficient and the r value was 0.78. The internal
      consistency was measured using Cronbach's alpha and item-total correlation and
      the r value was 0.789. The item discrimination analysis was also computed and the
      value was of above 0.35. These statistical measurements indicate that the CASHS
      was reliable. CONCLUSIONS: The CASHS is a valid and reliable tool that can be
      utilized for assessing the attitude of primary caregivers on home care of
      schizophrenics.

PMID- 24574562
TI  - Shared or induced obsessive compulsive disorder: Is it a reality?
AB  - BACKGROUND: Shared or induced obsessive compulsive disorder (OCD) is not yet a
      distinct diagnosis in classification of psychiatric disorders. In fact, though
      recognized as a diagnostic category, shared or induced psychotic disorders are
      rare and most of the literature is based on the case reports. MATERIALS AND
      METHODS: We are reporting three case studies manifested with shared or induced
      OCD (cases with obsessive symptoms that were shared from the primary case in
      their family). RESULTS: All the cases were treated considering shared or induced
      OCD as psychopathology. Response to treatment modalities in first and second case
      and poor response to treatment in third case is suggestive of shared or induced
      OCD as a distinct entity. It is different from shared psychosis in many ways.
      CONCLUSION: Shared or induced OCD is a distinct diagnosis. Greater awareness
      about this entity among mental health professionals is needed.

PMID- 24574563
TI  - Marchiafawa bignami disease possibly related to consumption of a locally brewed
      alcoholic beverage: Report of two cases.
AB  - Marchiafava Bignami disease is a rare toxic disease seen mostly in chronic
      alcoholics, resulting in progressive demyelination and necrosis of the corpus
      callosum. Initially it was thought to be specific to individuals in central
      Italy, consuming large amounts of Chianti red wine; however, alcoholic beverages
      worldwide are presently implicated. In our case series of two cases, locally made
      "illicit" liquor (Mahuwa Alcohol) could be the causative factor. In radiological
      point of view typically the corpus callosum is affected, with involvement of the
      body, genu, and splenium in order of occurrence. Occasionally the entire callosum
      may be also involved. Clinical presentation varies from case to case. 

PMID- 24574564
TI  - Methylphenidate and suicidal ideation: Report of two cases.
AB  - Stimulant prescriptions are routinely used to treat Attention Deficit
      Hyperactivity Disorder. Reports of psychiatric symptoms that have occurred
      include euphoria, delirium, confusion, toxic psychosis, and hallucinations. Here,
      authors report two cases of Attention Deficit Hyperactivity Disorder who were
      prescribed methylphenidate. Both children developed suicidal ideation that abated
      after discontinuing the drug. There were no depressive symptoms reported along
      with it, and the ideation could not be explained on the basis of impulsivity
      either. 

PMID- 24574565
TI  - Onset of schizophrenia at 100 years of age.
AB  - Although generally regarded as a disease of young adults, schizophrenia does
      occur in older ages. Doubts have been raised about the validity of diagnosing
      schizophrenia in very old age. We have described herein a rare and unique case of
      a woman who had onset of "schizophrenia" as per ICD-10 and DSM-IV-TR criteria at
      the age of 100 years. We have discussed about the validity of diagnosing
      schizophrenia in older age. 

PMID- 24574566
TI  - Body dysmorphic disorder: Borderline category between neurosis and psychosis.
AB  - Body dysmorphic disorder is an under-recognized chronic problem that has been
      established as an independent diagnostic entity. Its clinical features,
      comorbidity, course, and prognosis have been studied in detail. But, the issue of
      its psychotic and non-psychotic variants and the question of dimensional or
      categorical method of classifying this disorder still pose a diagnostic dilemma.
      This case report tries to highlight this issue. 

PMID- 24574568
TI  - Psyche and art: Art manifests to the soul that appreciates it.

PMID- 24574567
TI  - Pharmacotherapy of smoking cessation.
AB  - Nicotine in tobacco smoke causes not only pathophysiological changes in the
      smoker's body, but also develops tolerance to its own action with repeated use.
      Repeated exposure to nicotine develops neuroadaptation of the receptors,
      resulting in tolerance to many of the effects of nicotine. Pharmacotherapies for
      smoking cessation should reduce withdrawal symptoms and block the reinforcing
      effects of nicotine without causing excessive adverse effects. All forms of
      nicotine replacement therapy (NRT) - gum, patches and inhaler - and bupropion are
      safe and effective for increasing smoking cessation rates in the short and long
      term use. Combination NRT (more than one therapy) may be indicated in patients
      who have failed monotherapy. 

PMID- 24574570
TI  - Methodological considerations in studying psycho-social aspects of suicide: Reply
      to the criticism.

PMID- 24574569
TI  - Bilateral peripheral edema as a rare adverse effect of escitalopram.

PMID- 24574571
TI  - Culture-bound syndromes: Nosological and management issues.

PMID- 24574572
TI  - How psychiatrists get ridiculed in Hindi movies.

PMID- 24574573
TI  - Emergence of kleptomania during treatment for obsessive compulsive disorder with
      fluvoxamine.

PMID- 24574574
TI  - Sparse Estimation of Conditional Graphical Models With Application to Gene
      Networks.
AB  - In many applications the graph structure in a network arises from two sources:
      intrinsic connections and connections due to external effects. We introduce a
      sparse estimation procedure for graphical models that is capable of isolating the
      intrinsic connections by removing the external effects. Technically, this is
      formulated as a conditional graphical model, in which the external effects are
      modeled as predictors, and the graph is determined by the conditional precision
      matrix. We introduce two sparse estimators of this matrix using the reproduced
      kernel Hilbert space combined with lasso and adaptive lasso. We establish the
      sparsity, variable selection consistency, oracle property, and the asymptotic
      distributions of the proposed estimators. We also develop their convergence rate
      when the dimension of the conditional precision matrix goes to infinity. The
      methods are compared with sparse estimators for unconditional graphical models,
      and with the constrained maximum likelihood estimate that assumes a known graph
      structure. The methods are applied to a genetic data set to construct a gene
      network conditioning on single-nucleotide polymorphisms.

PMID- 24574575
TI  - Supporting Young Children With Multiple Disabilities: What Do We Know and What Do
      We Still Need To Learn?
AB  - Young children with multiple disabilities have unique needs and challenges. Many
      of these young children struggle to communicate their wants and needs, to freely
      move their body to access and engage their world, and to learn abstract concepts
      and ideas. Professionals and families working together must identify the
      individual supports each child needs to ensure that the young child with multiple
      disabilities is an active participant in all aspects of their lives and makes
      meaningful progress toward valued life outcomes.

PMID- 24574576
TI  - Dysmenorrhea and endometriosis in young women.
AB  - Dysmenorrhea is defined as symptoms associated with menstruation, such as
      abdominal pain, cramping and lumbago, that interfere with daily activity. Primary
      dysmenorrhea refers to menstrual pain without underlying pathology, whereas
      secondary dysmenorrhea is menstrual pain associated with underlying pathology.
      Endometriosis, one of the main causes of secondary dysmenorrhea, induces
      dysmenorrhea, pelvic pain and infertility, resulting in marked reduction of
      quality of life during reproductive age. This review article is a comprehensive
      overview of dysmenorrhea and endometriosis in young women. 

PMID- 24574577
TI  - Evaluation of a noise reduction procedure for chest radiography.
AB  - BACKGROUND: The aim of this study was to evaluate the usefulness of noise
      reduction procedure (NRP), a function in the new image processing for chest
      radiography. METHODS: A CXDI-50G Portable Digital Radiography System (Canon) was
      used for X-ray detection. Image noise was analyzed with a noise power spectrum
      (NPS) and a burger phantom was used for evaluation of density resolution. The
      usefulness of NRP was evaluated by chest phantom images and clinical chest
      radiography. We employed the Bureau of Radiological Health Method for scoring
      chest images while carrying out our observations. RESULTS: NPS through the use of
      NRP was improved compared with conventional image processing (CIP). The results
      in image quality showed high-density resolution through the use of NRP, so that
      chest radiography examination can be performed with a low dose of radiation.
      Scores were significantly higher than for CIP. CONCLUSION: In this study, use of
      NRP led to a high evaluation in these so we are able to confirm the usefulness of
      NRP for clinical chest radiography.

PMID- 24574578
TI  - Bepridil Suppresses Apoptosis in HL-1 Cardiac Atrial Myocytes Expressing Mutant
      E334K cMyBPC.
AB  - Besides its antiarrhythmic effect on atrial fibrillation, bepridil protects
      tissue, yet its effect on apoptosis has never been fully tested. We examine the
      effect of bepridil on apoptosis of HL-1 cells expressing E334K myosin-binding
      protein C (MyBPC), a model cell of apoptosis. Bepridil was compared with
      amiodarone, and its effects on the expression of pro- and anti-apoptotic protein
      and apoptosis of HL-1 cells expressing mutant E334K MyBPC-green fluorescent
      protein (GFP) was analyzed using Western blot and a flow cytometer. Bepridil
      decreased the protein levels of both Bax and cytochrome c of cells expressing
      E334K MyBPC-GFP with no changes in p53 and Bcl-2, while amiodarone decreased
      cytochrome c but did not influence Bax except in its highest concentration. It
      also decreased the number of Annexin-V positive cells of HL-1 cells expressing
      E334K MyBPC-GFP, and decreased apoptosis of HL-1 cells expressing E334K MyBPC
      GFP. 

PMID- 24574579
TI  - Reflection based Extraordinary Optical Transmission Fiber Optic Probe for
      Refractive Index Sensing.
AB  - Fiber optic probes for chemical sensing based on the extraordinary optical
      transmission (EOT) phenomenon are designed and fabricated by perforating
      subwavelength hole arrays on the gold film coated optical fiber endface. The
      device exhibits a red shift in response to the surrounding refractive index
      increases with high sensitivity, enabling a reflection-based refractive index
      sensor with a compact and simple configuration. By choosing the period of hole
      arrays, the sensor can be designed to operate in the near infrared
      telecommunication wavelength range, where the abundant source and detectors are
      available for easy instrumentation. The new sensor probe is demonstrated for
      refractive index measurement using refractive index matching fluids. The
      sensitivity reaches 573 nm/RIU in the 1.333~1.430 refractive index range.

PMID- 24574580
TI  - The privileged normalization of marijuana use - an analysis of Canadian newspaper
      reporting, 1997-2007.
AB  - The objective of this study was to systematically examine predominant themes
      within mainstream media reporting about marijuana use in Canada. To ascertain the
      themes present in major Canadian newspaper reports, a sample (N = 1999) of
      articles published between 1997 and 2007 was analyzed. Drawing from Manning's
      theory of the symbolic framing of drug use within media, it is argued that a
      discourse of 'privileged normalization' informs portrayals of marijuana use and
      descriptions of the drug's users. Privileged normalization implies that marijuana
      use can be acceptable for some people at particular times and places, while its
      use by those without power and status is routinely vilified and linked to deviant
      behavior. The privileged normalization of marijuana by the media has important
      health policy implications in light of continued debate regarding the merits of
      decriminalization or legalization and the need for public health and harm
      reduction approaches to illicit drug use.

PMID- 24574583
TI  - Cricoid pressure: An enigma wrapped in a mystery or a hand wrapped around a
      throat? If I can't disprove a lie, does it become the truth?

PMID- 24574581
TI  - IL-21 modulates release of proinflammatory cytokines in LPS-stimulated
      macrophages through distinct signaling pathways.
AB  - The aim of this study was to investigate the anti-inflammatory effect of IL-21 on
      LPS-induced mouse peritoneal macrophages. The results showed that IL-21
      significantly inhibited LPS-induced mRNA expression of IL-1beta, TNF-alpha, and
      IL-6 in macrophages, but not of IFN-gamma, IL-10, CCL5, or CXCL2. ELISA analysis
      showed that IL-21 also suppressed LPS-induced production of TNF-alpha and IL-6 in
      culture supernatants. Western blot analysis showed that IL-21 clearly inhibited
      ERK and IkappaBalpha phosphorylation and NF-kappaB translocation in LPS
      stimulated macrophages, but it increased STAT3 phosphorylation. Flow cytometric
      and Western blot analysis showed that IL-21 decreased M1 macrophages surface
      markers expression of CD86, iNOS, and TLR4 in LPS-stimulated cells. All results
      suggested that IL-21 decreases IL-6 and TNF-alpha production via inhibiting the
      phosphorylation of ERK and translocation of NF-kappaB and promotes a shift from
      the M1 to M2 macrophage phenotype by decreasing the expression of CD86, iNOS, and
      TLR4 and by increasing STAT3 phosphorylation in LPS-stimulated cells.

PMID- 24574582
TI  - Potent anti-inflammatory activity of pyrenocine A isolated from the marine
      derived fungus Penicillium paxilli Ma(G)K.
AB  - Very little is known about the immunomodulatory potential of secondary
      metabolites isolated from marine microorganisms. In the present study, we
      characterized pyrenocine A, which is produced by the marine-derived fungus
      Penicillium paxilli Ma(G)K and possesses anti-inflammatory activity. Pyrenocine A
      was able to suppress, both pretreatment and posttreatment, the LPS-induced
      activation of macrophages via the inhibition of nitrite production and the
      synthesis of inflammatory cytokines and PGE2. Pyrenocine A also exhibited anti
      inflammatory effects on the expression of receptors directly related to cell
      migration (Mac-1) as well as costimulatory molecules involved in lymphocyte
      activation (B7.1). Nitrite production was inhibited by pyrenocine A in
      macrophages stimulated with CpG but not Poly I:C, suggesting that pyrenocine A
      acts through the MyD88-dependent intracellular signaling pathway. Moreover,
      pyrenocine A is also able to inhibit the expression of genes related to NF kappa
      B-mediated signal transduction on macrophages stimulated by LPS. Our results
      indicate that pyrenocine A has promissory anti-inflammatory properties and
      additional experiments are necessary to confirm this finding in vivo model. 

PMID- 24574584
TI  - Cricoid pressure: Where do we stand?
AB  - In 1961, Sellick popularized the technique of cricoid pressure (CP) to prevent
      regurgitation of gastric contents during anesthesia induction. In the last two
      decades, clinicians have begun to question the efficacy of CP and therefore the
      necessity of this maneuver. Some have suggested abandoning it on the grounds that
      this maneuver is unreliable in producing midline esophageal compression.
      Moreover, it has been found that application of CP makes tracheal intubation and
      mask ventilation difficult and induces relaxation of the lower esophageal
      sphincter. There have also been reports of regurgitation of gastric contents and
      aspiration despite CP. Further, its effectiveness has been demonstrated only in
      cadavers; therefore, its efficacy lacks scientific validation. These concerns
      with the use of CP in modern anesthesia practice have been briefly reviewed in
      this article. 

PMID- 24574585
TI  - Considerations in perioperative assessment of valproic acid coagulopathy.
AB  - Valproic acid (VPA) is one of the widely prescribed antiepileptic drugs in
      children with multiple indications. VPA-induced coagulopathy may occur and
      constitute a pharmacological and practical challenge affecting pre-operative
      evaluation and management of patients receiving VPA therapy. This review
      summarizes the different studies documenting the incidence, severity and
      available recommendations related to this adverse effect. 

PMID- 24574587
TI  - Vitamin D and anesthesia: Is our present knowledge sufficient?

PMID- 24574586
TI  - Spinal anesthesia in children: A review.
AB  - Even after a vast safety record, the role of spinal anesthesia (SA) as a primary
      anesthetic technique in children remains contentious and is mainly limited to
      specialized pediatric centers. It is usually practiced on moribund former preterm
      infants (<60 weeks post-conception) to reduce the incidence of post-operative
      apnea when compared to general anesthesia (GA). However, there is ample
      literature to suggest its safety and efficacy for suitable procedures in older
      children as well. SA in children has many advantages as in adults with an added
      advantage of minimal cardio-respiratory disturbance. Recently, several reports
      from animal studies have raised serious concerns regarding the harmful effects of
      GA on young developing brain. This may further increase the utility of SA in
      children as it provides all components of balanced anesthesia technique. Also, SA
      can be an economical option for countries with finite resources. Limited duration
      of surgical anesthesia in children is one of the major deterrents for its
      widespread use in them. To overcome this, several additives like epinephrine,
      clonidine, fentanyl, morphine, neostigmine etc. have been used and found to be
      effective even in neonates. But, the developing spinal cord may also be
      vulnerable to drug-related toxicity, though this has not been systematically
      evaluated in children. So, adjuvants and drugs with widest therapeutic index
      should be preferred in children. Despite its widespread use, incidence of side
      effects is low and permanent neurological sequalae have not been reported with
      SA. Literature yields encouraging results regarding its safety and efficacy.
      Technical skills and constant vigilance of experienced anesthesia providers is
      indispensable to achieve good results with this technique. 

PMID- 24574589
TI  - Effect of intraoperative Dexmedetomidine infusion on Sevoflurane requirement and
      blood glucose levels during entropy-guided general anesthesia.
AB  - BACKGROUND: Dexmedetomidine has been shown to blunt the stress response to
      surgery. Hence a study was designed to evaluate the effect of intravenous (IV)
      Dexmedetomidine infusion during general anesthesia for abdominal surgeries on
      blood glucose levels and on Sevoflurane requirements during anesthesia. MATERIALS
      AND METHODS: Forty patients scheduled for abdominal surgery under general
      anesthesia were divided into Dexmedetomidine (D) group and Placebo (P) group of
      20 each. Group D received a loading dose of Inj. Dexmedetomidine at 1 MUg/kg/10
      min diluted to 20 mL, followed by maintenance with 0.5 MUg/kg/h., till the end of
      surgery. Group P received similar volume of IV normal saline. Anesthesia was
      maintained with nitrous oxide in oxygen and Sevoflurane keeping entropy between
      40 and 60. Data were analyzed using students t test, chi square test and Fisher
      Exact test as applicable. RESULTS: During the first postoperative hour,
      Dexmedetomidine group showed blood glucose levels of 118.2 +/- 16.24 mg/dL,
      compared to placebo group which was 136.95 +/- 19.76 mg/dL and it was
      statistically significant (P < 0.01). Mean hourly Sevoflurane requirement in
      Group D was 11.10 +/- 2.17 mL, compared to 15.45 +/- 3.97 mL in placebo group. In
      peri-operative period, the heart rate and MAP were significantly lower in Group
      D, when compared to placebo. Patients in Group D were better sedated and post
      operative pain score was better in Group D compared to Group P. CONCLUSION: IV
      Dexmedetomidine was effective in blunting stress response to surgical trauma as
      indicated by lower blood glucose levels, and reduces Sevoflurane requirements
      during entropy guided general anesthesia without affecting time for extubation.

PMID- 24574588
TI  - Effect of prophylactic vitamin D on anesthetic outcome in children with sickle
      cell disease.
AB  - BACKGROUND: Few previous studies proved that complications related to sickle cell
      disease (SCD) were common with regional anesthesia compared with general
      anesthesia while others reported no differences. This study was carried out to
      evaluate the role of prophylactic vitamin D on anesthetic outcome among male
      children with SCD undergoing circumcision. MATERIALS AND METHODS: A comparative
      study was carried out on 58 children undergoing circumcision with the regional
      block under light general anesthesia. The study sample was classified into two
      groups: one group received daily 400 IU vitamin D for 6 months before surgery
      while the other group without vitamin D. All patients were followed regarding the
      post-operative analgesia and the incidence of post-operative SCD related
      complications (acute chest syndrome, painful crisis and cerebrovascular
      accident). Data were analyzed with Statistical Package for Social Sciences
      version 13, produced by IBM SPSS, Inc. in Chicago, Illinois, USA. RESULTS: There
      was a highly significant difference between the two groups (P < 0.001) regarding
      first analgesic request and total analgesic consumption per day: there was
      delayed analgesic request and less total analgesic consumption per day in vitamin
      D group. Comparison of post-operative sedation scores showed highly significant
      difference (P < 0.001) between the two groups, Sedation scores was increased
      significantly in vitamin D group. This study also reported that the
      administration of vitamin D was associated with less noticeable post-operative
      SCD complications. CONCLUSION: The use of prophylactic vitamin D in SCD will
      result in delayed post-operative analgesic request and less total analgesic
      requirement. Administration of vitamin D was also associated with less post
      operative complications.

PMID- 24574590
TI  - Comparison of the effects of dexmedetomidine-ketamine and sevoflurane-sufentanil
      anesthesia in children with obstructive sleep apnea after
      uvulopalatopharyngoplasty: An observational study.
AB  - BACKGROUND: Children with obstructive sleep apnea (OSA) are particularly at risk
      under anesthesia after uvulopalatopharyngoplasty (UPPP). This prospective
      randomized double-blind study focused on the comparison of dexmedetomidine
      ketamine and sevoflurane-sufentanil anesthesia on children with respect to
      safety, feasibility, and clinical effects. MATERIALS AND METHODS: A total of 60
      children, aged 2-10 years, classified as American Society of Anesthesiologists
      (ASA) status I and II scheduled for UPPP were prospectively studied. Patients
      were randomly allocated to receive either dexmedetomidine-ketamine-based
      anesthesia (group DK, n = 30) or sevoflurane-sufentanil-based anesthesia (group
      SS, n = 3 0). Heart rate (HR) and systolic blood pressure during the first 60 min
      of the procedure, Ramsay sedation score, the Pediatric Anesthesia Emergence
      Delirium (PAED) scale and a 5-point scale used to evaluate emergence agitation
      (EA) in postanesthesia care unit (PACU) and postoperative outcomes data were
      recorded. RESULTS: During the first 60 min of anesthesia, mean HR, and mean
      diastolic noninvasive arterial blood pressure (NIBP) were not statistically
      different in the two groups (P > 0.05) Compared with group SS, the patients in
      group DK had lower rescue tramadol requirement and lower pain score, PAED score,
      and EA score at 5, 10, 15, and 30 min in PACU; but had a higher Ramsay scale at
      10, 15, 30, 45, and 60 min in PACU and the incidence of SpO2 below 95%, also the
      time of first bowel movement and ambulation in group DK was shorter. CONCLUSIONS:
      The dexmedetomidine-ketamine combination was not superior to a sevoflurane
      sufentanil combination because of late awake time and a high potential for
      adverse respiratory events in PACU, the benefit of dexmedetomidine administration
      being a decreased incidence of EA and a lower recovery time of bowel movement and
      ambulation.

PMID- 24574591
TI  - Dexmedetomidine prolongs the effect of bupivacaine in supraclavicular brachial
      plexus block.
AB  - BACKGROUND: We compared the effects of adding dexmedetomidine to a 30 ml solution
      of 0.325% bupivacaine in supraclavicular brachial plexus block. Onset and
      duration of sensory and motor block along with the duration of analgesia were the
      primary endpoints. MATERIALS AND METHODS: Fifty patients posted for upper limb
      surgeries were enrolled for a prospective, randomized, double-blind, placebo
      controlled trial. Patients were divided into two groups, the control group S and
      the study group SD. In group S (n = 25), 30 ml of 0.325% bupivacaine + 1 ml
      normal saline; and in group SD (n = 25), 30 ml of 0.325% bupivacaine + 1 ml (100
      MUg) dexmedetomidine were given for supraclavicular brachial plexus block using
      the peripheral nerve stimulator. Onset and duration of sensory and motor blocks
      were assessed along with the duration of analgesia, sedation, and adverse
      effects, if any. Hemodynamic parameters, like heart rate (HR), systolic arterial
      blood pressure (SBP), and diastolic arterial blood pressure (DBP) were also
      monitored. RESULTS: Demographic data and surgical characteristics were comparable
      in both the groups. The onset times for sensory and motor blocks were
      significantly shorter in SD than S group (P < 0.001), while the duration of
      blocks was significantly longer (P < 0.001) in SD group. Except for the initial
      recordings (at 0, 5, 10, and 15 min), heart rate levels in group SD were
      significantly lower (P < 0.001). SBP and DBP levels in SD group at 15, 30, 45,
      60, 90 and 120 min were significantly lower than in S group (P < 0.001). In fact,
      when the percentage changes in HR/SBP/DBP were compared from 0-5/0-10/0-15/0-30/0
      45/0-60/0-90/0-120 min in SD with S group, they came out to be highly significant
      (P < 0.001) in group SD. The duration of analgesia (DOA) was significantly longer
      in SD group than S group (P < 0.001). Except that, bradycardia was observed in
      one patient in the group SD, no other adverse effects were observed in either of
      the groups. CONCLUSION: Dexmedetomidine added as an adjuvant to bupivacaine for
      supraclavicular brachial plexus block significantly shortens the onset time and
      prolongs the duration of sensory and motor blocks and duration of analgesia.
      Patients in group SD were adequately sedated (modified Ramsay Sedation Score, RSS
      = 2/6 or 3/6) with no adverse effects except bradycardia in one patient of group
      SD.

PMID- 24574592
TI  - Comparison of inguinal versus classic approach for obturator nerve block in
      patients undergoing transurethral resection of bladder tumors under spinal
      anesthesia.
AB  - BACKGROUND: Selective obturator nerve blockade (ONB) is an effective option to
      prevent adductor spasm during transurethral resection of bladder tumors (TURBT)
      involving the lateral wall under spinal anesthesia (SA). The classic approach is
      less popular as the obturator nerve is deep seated and associated with vascular
      injury. The inguinal approach was described as a safer alternative. This
      randomized clinical study was undertaken to compare the ease of block, the
      success rate and complications of the classic pubic and superficial inguinal
      approach for ONB. MATERIALS AND METHODS: A total of 30 patients scheduled to
      undergo TURBT under SA were administered bilateral ONB. Inguinal approach
      recently described by Choquet was performed on one side and classic approach
      described by Labat was performed on the other side in random order using a nerve
      stimulator. The ease of block, success rate (number of attempts to accomplish the
      block) and complications were noted and compared between both the approaches. Chi
      square analysis was performed to compare the ease of approach of the two
      techniques. Non-parametric analyses using Mann Whitney test was used to compare
      the number of attempts to accomplish the block in each approach. A value of P <
      0.05 was considered statistically significant. RESULTS: The ease of block (P =
      0.09) and the median number of attempts to accomplish the block (P = 0.45) were
      comparable between the two approaches. The incidence of vascular injury was
      higher in classic approach (P = 0.056). CONCLUSIONS: Inguinal approach is a
      useful alternative to classic approach block for patients undergoing TURBT under
      SA.

PMID- 24574593
TI  - Comparative study of epidural application of morphine versus gelfoam soaked in
      morphine for lumbar laminectomy.
AB  - BACKGROUND: Epidural application of morphine has been used for postoperative
      analgesia following spine surgery but short duration of action of single
      application limits its widespread use. MATERIALS AND METHODS: One hundred and
      fifty patients undergoing lumbar laminectomy were randomly allocated to two
      groups of 75 patients each. Anesthetic technique was standardized in both the
      groups. In Group I, at the completion of laminectomy, a 5 * 1-cm strip of gelfoam
      soaked in 5 mg morphine (1 mg/ml) was contoured to be placed in the epidural
      space whereas, in group II, gelfoam soaked in saline was placed in the epidural
      space and 5 mg morphine (1mg/ml) was instilled over the intact epidural space.
      Analgesic consumption for 48 hours, time-of first analgesic request, time of
      ambulation, time of discharge from post anesthesia care unit (PACU) and hospital
      and adverse effects were recorded. The data was analyzed using appropriate
      statistical tests. RESULTS: Mean analgesic consumption in 48 hours was
      significantly less in group I (8.47 +/- 3.674 mg) as compared to group II (24.80
      +/- 6.009 mg). Supplemental analgesia was requested at 30.03 +/- 6.796 hours in
      Group I, vs 10.25 +/- 2.243 in group II (P < 0.001). Group I patients were
      discharged earlier from PACU as compared to group II (P < 0.001) though time of
      discharge from hospital was similar in both the groups. There were no major
      adverse effects except pruritis, which was observed in 30.6% patients in group I
      and 37.3% in group II (statistically insignificant (P > 0.01)). CONCLUSION:
      Epidural application of morphine soaked in gelfoam is an effective method for
      prolonging the postoperative analgesia after spine surgery.

PMID- 24574594
TI  - Is midazolam superior to triclofos and hydroxyzine as premedicant in children?
AB  - BACKGROUND: Search for an ideal premedicant drug for children is still on. A
      prospective, randomized trial was conducted to compare the efficacy of midazolam,
      triclofos and hydroxyzine as premedication in children undergoing lower abdominal
      surgeries. MATERIALS AND METHODS: Sixty American Society of Anesthesiologists I
      or II patients 2-8 years of age, scheduled for elective lower abdominal surgery
      were included. The patients were randomly divided into three groups M, T and H of
      20 children each who received midazolam 0.5 mg/kg, triclofos 75 mg/kg and
      hydroxyzine 0.5 mg/kg respectively, orally 60 min before surgery. The
      acceptability of drugs, level of sedation, anxiety during separation and on mask
      application was assessed. RESULTS: The acceptability of midazolam and hydroxyzine
      was better than triclofos. Hydroxyzine was found to have lesser sedative effect
      as compared to both midazolam and triclofos. No major adverse effects were
      observed. CONCLUSION: Midazolam was found to be a better premedicant in terms of
      sedation, anxiolysis and safety.

PMID- 24574595
TI  - Oral bisoprolol improves surgical field during functional endoscopic sinus
      surgery.
AB  - BACKGROUND: The success of functional endoscopic sinus surgery (FESS) depends on
      visual clarity of the surgical field, through the endoscope. The objective of
      this double-blind, randomized, controlled study was to determine if a pre
      operative dose of bisoprolol (2.5 mg) would reduce the bleeding during FESS and
      improve the visualization of the operative field. MATERIALS AND METHODS: Thirty
      American Society of Anesthesiologists I or II patients, scheduled for FESS were
      randomized to receive either a placebo (Group A) or 2.5 mg of bisoprolol (Group
      B) 90 min prior to the surgery. All the patients received standard anesthesia and
      monitoring. The aim was to maintain the mean arterial pressure (MAP) of 60-70
      mmHg, by titrating dose of isoflurane and fentanyl. The concentration of
      isoflurane used was recorded every 15 min. At the end of the surgery, the volume
      of blood loss was measured and the surgeon was asked to grade the operative field
      as per the Fromme-Boezaart Scale. RESULT: The blood loss was significantly (P <
      0.0001) more in the control group (398.67 +/- 228.79 ml) as compared with that in
      the bisoprolol group (110.67 +/- 45.35 ml). The surgical field was graded better
      in those who received bisoprolol as compared with those in the control group (P -
      0.0001). The volume percent of isoflurane and the dose of fentanyl used was
      significantly lower in those who received bisoprolol. During the operative
      period, the MAPs were 70.0 +/- 2.7 (Group A) and 62.6 +/- 3.6 mmHg (Group B) and
      the heart rate was 99.8 +/- 5.0/min (Group A) and 69.2 +/- 4.4/min (Group B).
      These differences were statistically significant ( P - 0.001). CONCLUSION: This
      clinical trial has demonstrated that administration of a single pre-operative
      dose of bisoprolol (2.5 mg) can significantly reduce the blood loss during FESS
      and improve the visualization of the operating field.

PMID- 24574596
TI  - High-frequency percussive ventilation in severe acute respiratory distress
      syndrome: A single center experience.
AB  - BACKGROUND: Few studies have investigated high-frequency percussive ventilation
      (HFPV) in adult patients with acute respiratory distress syndrome (ARDS).
      MATERIALS AND METHODS: We retrospectively analyzed data from critically ill
      patients with moderate and severe ARDS who received HFPV. Ventilation and
      oxygenation were governed according to a predefined protocol. HFPV was continued
      until patients could be switched to conventional ventilation. RESULTS: A total of
      42 patients (20 with pneumonia-related ARDS and 22 non-septic ARDS cases) were
      evaluable. Baseline demographic characteristics, severity of illness, lung injury
      score; pH and respiratory variables were comparable between pneumonia and non
      sepsis-related ARDS. Within 24 h, HFPV restored normal pH and PaCO2 and
      considerably improved oxygenation. Oxygenation improved more in non-septic than
      in pneumonia-related ARDS. Patients with pneumonia-induced ARDS also remained
      longer HFPV-dependent (7.0 vs. 4.9 days; P < 0.05). Mortality at 30 days was
      significantly higher in pneumonia-related than in non-sepsis-related ARDS (50%
      vs. 18%; P = 0.01). CONCLUSIONS: HFPV caused rapid and sustained improvement of
      oxygenation and ventilation in patients with moderate to severe ARDS. Less
      improved oxygenation, longer ventilator dependency and worse survival were
      observed in pneumonia-related ARDS.

PMID- 24574597
TI  - Significantly reduced hypoxemic events in morbidly obese patients undergoing
      gastrointestinal endoscopy: Predictors and practice effect.
AB  - BACKGROUND: Providing anesthesia for gastrointestinal (GI) endoscopy procedures
      in morbidly obese patients is a challenge for a variety of reasons. The negative
      impact of obesity on the respiratory system combined with a need to share the
      upper airway and necessity to preserve the spontaneous ventilation, together add
      to difficulties. MATERIALS AND METHODS: This retrospective cohort study included
      patients with a body mass index (BMI) >40 kg/m(2) that underwent out-patient GI
      endoscopy between September 2010 and February 2011. Patient data was analyzed for
      procedure, airway management technique as well as hypoxemic and cardiovascular
      events. RESULTS: A total of 119 patients met the inclusion criteria. Our
      innovative airway management technique resulted in a lower rate of intraoperative
      hypoxemic events compared with any published data available. Frequency of
      desaturation episodes showed statistically significant relation to previous
      history of obstructive sleep apnea (OSA). These desaturation episodes were found
      to be statistically independent of increasing BMI of patients. CONCLUSION: Pre
      operative history of OSA irrespective of associated BMI values can be potentially
      used as a predictor of intra-procedural desaturation. With suitable modification
      of anesthesia technique, it is possible to reduce the incidence of adverse
      respiratory events in morbidly obese patients undergoing GI endoscopy procedures,
      thereby avoiding the need for endotracheal intubation.

PMID- 24574598
TI  - Impact of an educational intervention on errors in death certification: An
      observational study from the intensive care unit of a tertiary care teaching
      hospital.
AB  - BACKGROUND: A high incidence of errors occur while filling up death certificates
      in hospitals. The purpose of this study was to analyze the impact of an
      educational intervention on errors in death certification in an intensive care
      unit (ICU). Patients admitted to ICUs by virtue of being critically ill have a
      higher mortality than other hospitalized patients. This study was designed to see
      if any improvement could be brought about in filling death certificates.
      MATERIALS AND METHODS: Educating sessions, interactive workshops, and monthly
      audits for the department resident doctors were conducted. One hundred and fifty
      death certificates were audited for major and minor errors (75 before and 75
      after the educational intervention) over a period of 18 months. Fisher's exact
      test was applied to statistically analyze the data. RESULTS: There was a
      significant decrease in major errors like mechanism without underlying cause of
      death (60.0 vs. 14.6%, P < 0.001), competing causes (88.0 vs. 13.3%, P < 0.001),
      and improper sequencing (89.3 vs. 36.0%, P < 0.001). There was also a significant
      decrease in minor errors such as use of abbreviations (89.3 vs. 29.3%, P < 0.001)
      and no time intervals (100.0 vs. 22.6%, P < 0.001). CONCLUSION: Authors conclude
      that death certification errors can be significantly reduced by educational
      interventional programs.

PMID- 24574599
TI  - A survey of undergraduate anesthesia rotation in medical colleges of Pakistan.
AB  - BACKGROUND: Student perceptions of specialties influence career choice decisions.
      It is important to expose undergraduates to the scope of rewarding careers in
      specialties like anesthesia by ensuring a good quality educational experience
      during anesthesia rotation. Our objective was to survey the curriculum structure
      and placement of the anesthesia undergraduate rotation in all the medical
      colleges of Pakistan recognized by the Pakistan Medical and Dental Council.
      MATERIALS AND METHODS: A standardized survey questionnaire was distributed by
      direct contact, postal mail or e mail to one identified anesthetist in all
      recognized medical colleges with enrolment of 100 or more students. The response
      rate was 75%. We received responses by hand, email and postal mail. RESULTS: We
      received responses from 15 out of 20 anesthetists contacted. 11 reported
      undergraduate anesthesia rotation while 4 reported absence of this rotation in
      their undergraduate curriculum. The rotation placement, duration and curriculum
      showed a wide variation and lack of standardization. CONCLUSION: Our survey
      indicates that the inclusion of anesthesia rotation in undergraduate medical
      education is not mandatory and standardized. The rotation duration, placement and
      curriculum need to be standardized to enhance the quality of the experience and
      promote the scope of the specialty for rewarding careers.

PMID- 24574600
TI  - Dapsone-induced methemoglobinemia: "Saturation gap"-The key to diagnosis.
AB  - Two cases of Acquired Methemoglobinemia are presented. The significance of a high
      index of suspicion for diagnosisis emphasized, especially in the presence of a
      "saturation gap". The various causes of acquired methemoglobinemia are enumerated
      and the management reviewed. 

PMID- 24574601
TI  - Platelet cold agglutinins and thrombocytopenia: A diagnostic dilemma in the
      intensive care unit.
AB  - We report a case of pseudo-thrombocytopenia due to cold agglutinins against
      platelets. These cold agglutinins were the cause for diagnostic confusion and
      resulted in extensive workup and unnecessary therapeutic precautions. A thirty
      two year old female with Guillain-Barre syndrome was admitted in the ICU and
      serial work-up showed markedly low levels of platelets. The patient had no
      symptoms of bleeding and patient was investigated extensively for deciphering the
      etiology of low platelet count. In-vitro clumping of platelets was suspected and
      in-vitro studies showed marked clumping of platelets with ethylene-diamine-tetra
      acetic acid, citrate and heparinized samples. The manual platelet count was found
      to be within normal limits. Thrombocytopenia as a result of platelet cold
      agglutinins is a rare cause of in-vitro low platelet counts. No clinical problems
      have been reported due to the same. 

PMID- 24574602
TI  - Bronchoscopic topical steroid instillation in prevention of tracheal stenosis.
AB  - Corrosive acid poisoning commonly results in chemical injuries to respiratory and
      upper gastrointestinal tract. Corrosive mucosal erosion of the larynx and trachea
      may occur if the patient aspirates acid. We successfully used local anti
      inflammatory action of dexamethasone instilled through a fiber-optic bronchoscope
      for regression of mucosal edema and prevention of subsequent development of
      stricture in a young female. 

PMID- 24574603
TI  - Peri-operative dexamethasone therapy and post-operative psychosis in patients
      undergoing major oral and maxillofacial surgery.
AB  - A broad array of behavioral symptoms, including psychosis, can transpire post
      operatively following a variety of surgeries. It is difficult to diagnose the
      exact cause of post-operative psychosis. We report three cases, which developed
      psychosis post-operatively after undergoing major oral and maxillofacial
      surgeries. All the three patients were administered dexamethasone peri
      operatively. Dexamethasone is used to prevent or reduce post-operative edema. The
      exact dose of dexamethasone, which can cause psychosis, is unknown. It is
      important to raise awareness about this potential complication so that measures
      for management can be put in place in anticipation of such an event. 

PMID- 24574604
TI  - Esophageal polyp as a posterior mediastinal mass: Intraoperative dynamic airway
      obstruction requiring emergency tracheostomy.
AB  - Anesthesia in the presence of a mediastinal mass is difficult and challenging as
      the mass can involve or compress the heart, great vessels, tracheo-bronchial tree
      and the surrounding structures. We describe a case of severe tracheo-bronchial
      obstruction requiring emergency tracheostomy during the intraoperative period
      after an uneventful induction of anesthesia in a patient with a large esophageal
      polyp presenting as a posterior mediastinal mass. 

PMID- 24574605
TI  - Role of newer imaging modalities for airway assessment in dynamic tracheal
      compression.
AB  - Anesthetic management of a patient with tracheal stenosis is challenging. Though
      we have newer imaging modalities like multislice, three-dimensional computerized
      tomography, virtual bronchoscopy to determine the size and anatomy of the airway,
      it is difficult to accurately predict the distensibility of the trachea with the
      available preoperative tests. With our experience in this case, we believe that
      newer imaging modalities are just an adjunct in the assessment of the compromised
      airway in case of dynamic compression. Clinical assessment is very important in
      deciding the plan of management. 

PMID- 24574606
TI  - Anaphylaxis from atracurium without skin manifestation.
AB  - Anaphylaxis is an acute, potentially fatal allergic reaction involving multi
      organ system that is triggered by a wide range of antigens with a subsequent
      release of chemical mediators from mast cells and basophils. Diagnosis is
      primarily clinical though laboratory studies are helpful in further confirmation.
      Anaphylactic reactions during anesthesia are rare, but can be fatal if not
      promptly recognized and treated. Among all drugs commonly used in anesthesia,
      muscle relaxants are the most notorious to trigger anaphylactic reactions and
      benzylisoquinolinium group of drugs are known to be less common an offender than
      the steroidal compounds. We report severe anaphylactic reaction after
      administration of atracurium that was promptly diagnosed and managed without any
      further morbidity. 

PMID- 24574607
TI  - Successful living donor kidney transplantation in a patient with prothrombin gene
      mutation: Case report and literature review.
AB  - We present a patient with known prothrombin gene mutation and a history of prior
      vascular events, who underwent living donor kidney transplantation. Given the
      presumed elevated risk of complication from known prothrombin mutation, clinical
      management was directed towards optimizing living donor allograft function. 

PMID- 24574608
TI  - Obtaining airtight seal with plastic infusion bottle using conventional
      intravenous set.

PMID- 24574609
TI  - Airway complication due to retropharyngeal spread of epidural abscess during
      prone position.

PMID- 24574610
TI  - An effective pharmacological management of postburn hypertrophic scar pain.

PMID- 24574611
TI  - Transient compressive lumbar radiculopathy following post-epidural blood patch.

PMID- 24574612
TI  - Reply to: Management of intraoperative hiccups with intravenous promethazine.

PMID- 24574613
TI  - Providing anesthesia in a remote location for radiation oncology in an adult -
      Problems and solutions.

PMID- 24574614
TI  - Prallethrin poisoning that taxes the brain.

PMID- 24574615
TI  - Anesthetic management of a child with Bardet-Biedl syndrome undergoing post
      auricular dermoid excision.

PMID- 24574617
TI  - Spontaneous ventilation and not controlled ventilation for removal of foreign
      body when present in both bronchi in a child.

PMID- 24574616
TI  - Hyoscine-N-butylbromide induced ventricular tachycardia during ERCP.

PMID- 24574618
TI  - Move the anesthesia workstation cautiously!

PMID- 24574619
TI  - Subglottic stenosis and acute airway obstruction.

PMID- 24574620
TI  - Life-threatening severe sepsis following stapled hemorrhoidopexy.

PMID- 24574621
TI  - Management of anesthesia in biotinidase deficiency.

PMID- 24574622
TI  - Spouses as kidney donors in India: Trends and outcomes.

PMID- 24574623
TI  - Outcomes of spousal versus related donor kidney transplants: A comparative study.
AB  - This study was designed to compare the outcomes of spousal donor (SD) with
      related donor (RD) kidney transplants performed at our center between January
      2010 and October 2012. A total of 323 adult, ABO-compatible kidney transplants
      (SD 150 [46.4%], RD 173 [53.6%]) were included. Data on outcomes at 6 months post
      transplant was collected retrospectively (2010-2011) and prospectively (January
      October 2012). Majority of the donors (SD 88%, RD 72.2%) were females. In the SD
      group, donors were younger (SD 35.6 +/- 8.2 years, RD 45.2 +/- 11.5 years; P <
      0.0001), whereas recipients were older (SD 42.2 +/- 8.3 years, RD 30.0 +/- 9.5
      years; P < 0.0001). A significantly higher proportion of patients in the SD group
      were given induction therapy (43% vs 12%; P < 0.001). Biopsy proven acute
      rejections were more common in the RD group (16% vs 28.3%; P = 0.01). Majority
      (80.8%) of the acute rejections occurred in the first 2 weeks post-transplant in
      both groups. Isolated acute cellular rejections (ACRs) and isolated antibody
      mediated rejections constituted 50% and 25% of rejection episodes in both groups,
      whereas the remainder had histological evidence of both. The proportion of
      steroid responsive ACRs was similar in both groups (SD 83.3%, RD 65.4%; P = 0.2).
      The number of patients with abnormal graft function at the end of the study was
      higher in the RD group (2.3% vs. 12.3%; P = 0.001). Patient survival and
      infection rates were similar in the two groups. We conclude that short-term
      outcomes of SD transplants are not inferior to RD transplants. Lesser use of
      induction therapy in the RD group may explain the poorer outcomes as compared to
      the SD group. 

PMID- 24574624
TI  - Outcome of live and deceased donor renal transplantation in patients aged >=55
      years: A single-center experience.
AB  - Renal transplantation (RTx) has now become an accepted therapeutic modality of
      choice for elderly ESRD patients. This single-center study was undertaken to
      evaluate the outcome of RTx in ESRD patients >=55 years. A total of 103 patients
      underwent RTx 79 living related living donors [LD], 24 deceased donors [DD]) at
      our center. Post-transplant immunosuppression consisted of calcineurin inhibitor
      based regimen. The mean donor age was 58.3 years in the LD group and 59.5 years
      in the DD group. Male recipients constituted 92% in LD and 75% in DD group. In
      living donor renal transplantation, 1- and 5-year patient survival was 93% and
      83.3% respectively and death-censored graft survival was 97.3% and 92.5%
      respectively. There were 12.6% biopsy proven acute rejection (BPAR) episodes and
      12.6% patients were lost, mainly due to infections. In deceased donor renal
      transplantation, 1- and 5-year patient survival was 79.1% and 74.5% respectively
      and death-censored graft survival was 95.8% and 85.1% respectively. There were
      12.5% BPAR episodes and 25% of patients were lost, mainly due to infections. RTx
      in ESRD (>=55 years) patients has acceptable patient and graft survival if found
      to have cardiac fitness and therefore should be encouraged. 

PMID- 24574625
TI  - Correlation of serum phosphate with carotid intimal-medial thickness in chronic
      kidney disease patients.
AB  - While increased serum phosphate concentration is a significant risk factor for
      vascular calcification, it is unclear whether serum phosphate is also a risk
      factor for increased arterial wall thickness in chronic kidney disease (CKD)
      patients. Using B-mode ultrasonography, we examined carotid intimal-medial
      thickness (CIMT) of CKD patients and analyzed risk factors for increased IMT with
      regard to the effect of serum phosphate. One hundred patients were enrolled (73
      patients without diabetes, 27 patients with diabetes; 57 men, 43 women; age, 46.2
      +/- 15.3 years). CIMT of patients with diabetes was significantly greater than
      that of patients without diabetes (0.78 +/- 0.250 versus 0.66 +/- 0.178 mm; P <
      0.0001). For the group of all patients, CIMT correlated strongly and
      significantly with serum phosphate (r = 0.911; P < 0.001). In multiple regression
      analysis serum phosphate level (beta = 0.356; <0.0001) was found to be a
      significant independent risk factor for increased CIMT, in addition to other
      independent risk factors, including advanced age, higher systolic blood pressure,
      urinary albumin and the presence of diabetes (R2 = 0.956; P < 0.00001). In
      conclusion, high serum phosphate level is a significant and independent factor
      associated with advanced arteriosclerosis in CKD patients with and without
      diabetes in addition to advanced age. 

PMID- 24574626
TI  - Anesthetic management in parturients with chronic kidney disease undergoing
      elective Caesarean delivery: Our experience of nine cases.
AB  - In this retrospective study, we describe the anesthetic management and its
      implications in parturients with chronic kidney disease (CKD; n = 9), who
      underwent elective caesarean delivery. Nine parturients with CKD of various
      etiologies, who underwent elective Caesarean delivery, were included in this
      study. Spinal anest-hesia was administered in all parturients with normal
      coagulation profile through a 25-gauze spinal needle (Quincke) with 0.5% (H)
      bupivacaine in L2-3 space and T6 level was achieved. Hemodynamics and side
      effects such as nausea, vomiting, headache, and backache were record. The mean
      age was 28.22 +/- 4.43 years. The mean levels of serum creatinine and serum
      potassium were 2.78 +/- 1.29 mg/dl and 4.11 +/- 0.46 meq/l, respectively. Mean
      baseline values of systolic blood pressure, diastolic blood pressure, and pulse
      rate were higher which decreased after spinal anesthesia. However, the incidence
      of hypotension, which required mephentermine treatment, was 11.1%. One patient
      had symptoms of nausea and vomiting/dizziness at the time of hypotension, which
      disappeared after treatment with 5 mg of intravenous mephentermine. Baseline
      value of PR remained high throughout the operation. Parturients with CKD with
      normal coagulation profile remained hemodynamically stable under spinal
      anesthesia with minimal side effects. However, a large number of studies are
      required to determine the safety of spinal anesthesia in this setting. 

PMID- 24574627
TI  - Thrombotic microangiopathy in renal allografts.
AB  - Thrombotic microangiopathy (TMA) is a serious complication of renal
      transplantation. It is a morphological expression of various etiological factors.
      In a renal allograft, TMA can occur de novo or be a recurrent disease. The aim of
      this study was to analyze the etiological factors and observe the changing trends
      of TMA with respect to emerging new etiological factors. We evaluated 131 graft
      biopsies over a period of 21/2 years (2010-2012). All the renal biopsies were
      formalin fixed, paraffin embedded. Twenty serial sections were studied. Stains
      routinely used were Hematoxylin and Eosin, Periodic Acid Schiff, Massons
      Trichrome and Silver Methenamine stains. C4d by immunohistochemical method was
      done on all graft biopsies. Incidence of TMA in our series was 9.1%. Out of the
      12 cases, five were associated with calcineurin inhibitor toxicity, three were
      diagnosed as acute antibody-mediated rejection, and two were recurrent haemolytic
      uremic syndrome. One patient developed haemolytic uremic syndrome on treatment
      with sirolimus and one patient was cytomegalovirus positive on treatment with
      ganciclovir, developed haemolytic uremic syndrome during treatment course. This
      study describes a spectrum of etiological factors for thrombotic mciroangiopathy
      ranging from common cause like calcineurin inhibitor toxicity to rare cause like
      ganciclovir induced TMA. 

PMID- 24574628
TI  - Posterior reversible encephalopathy syndrome in children with kidney disease.
AB  - Posterior reversible encephalopathy syndrome (PRES) is a clinic-radiographic
      entity of heterogeneous etiologies that are grouped together because of similar
      findings on neuro-imaging and associated symptom complex of headache, vision
      loss, altered mentation, and seizures. Although usually considered benign and
      reversible, characteristics of this syndrome in pediatric patients remain
      obscure. This case series included 11 patients (8 males, 3 females, age 3-15
      years) of PRES during September 2010 to February 2012 out of a total 660 renal
      pediatric patients (1.66%). We studied their clinical profile, contributory
      factors, and outcome. Presenting symptoms were headache in 73%, dimness of vision
      or cortical blindness in 36%, seizures in 91%, and altered mentation in 55%. The
      associated renal diseases were acute renal failure (55%), chronic renal failure
      (9%), and 36% had normal renal function. The contributory factors were
      uncontrolled hypertension (100%), severe hypoproteinemia (9%), persistent
      hypocalcemia (9%), hemolytic uremic syndrome (36%), cyclosporine toxicity (9%),
      lupus nephritis (9%), high hematocrit (9%), and pulse methylprednisolone (9%).
      Brain imaging showed involvement of occipito-parietal area (100%) and other brain
      areas (63%). All but one patient of hemolytic uremic syndrome had complete
      clinical neurological recovery in a week, and all had normal neurological imaging
      after 4-5 weeks. PRES is an underdiagnosed entity in pediatric renal disease
      patients. Associated hypertension, renal disease, and immunosuppressive treatment
      are important triggers. Early diagnosis and treatment of comorbid conditions is
      of prime importance for early reversal of syndrome. 

PMID- 24574629
TI  - Hemolytic uremic syndrome associated with Plasmodium vivax malaria successfully
      treated with plasma exchange.
AB  - We report a case of hemolytic uremic syndrome (HUS) in an adult patient with
      Plasmodium vivax malaria. The patient presented with worsening anemia, persistent
      thrombocytopenia and acute kidney injury. HUS was diagnosed based on the high
      serum lactate dehydrogenase, elevated reticulocyte count and presence of
      schistocytes on peripheral blood smear. Kidney biopsy showed features of
      thrombotic microangiopathy. Complete hematological remission was achieved after
      five sessions of therapeutic plasma exchange. Renal function partially recovered
      and stabilized at discharge. Vivax malaria, generally considered benign, may be
      rarely associated with HUS. 

PMID- 24574630
TI  - Partially thrombosed aneurysm of the abdominal aorta: Unusual cause of chronic
      inflammation and resistance to recombinant human erythropoietin.
AB  - Diagnosis of chronic inflammatory syndrome is often a challenge. In dialysis
      patients, this condition leads to resistance to recombinant human erythropoietin
      (rHuEPO). We here report a case of a 72-year-old male undergoing chronic
      hemodialysis and developed rHuEPO resistance without any obvious etiology.
      Investigations showed a partially thromosed aneurysm of the infrarenal aorta.
      Antiplatelet therapy was started with a satisfactory outcome. 

PMID- 24574631
TI  - Plasmablastic myeloma presenting as rapidly progressive renal failure in a young
      adult.
AB  - Multiple myeloma (MM) is a condition where there is malignant proliferation of
      plasma cells. There is a strong correlation with age, peaking at 60-70 years. The
      clinical course in adolescents and young individuals is generally indolent and
      the survival is longer. We report a case of a 28-year-old male, who was diagnosed
      to have plasmablastic myeloma, an atypical variant of MM with a poor prognosis,
      presenting as rapidly progressive renal failure. He was given induction
      chemotherapy and then underwent autologous peripheral blood stem cell
      transplantation. 

PMID- 24574632
TI  - Successful three-way kidney paired donation transplantation: The first Indian
      report.
AB  - Providing transplantation opportunities for patients with incompatible live
      donors through kidney paired donation (KPD) is an important strategy for easing
      the crisis in organ availability. KPD is can overcome the barriers when the only
      living potential donors are deemed unsuitable owing to an incompatibility of
      blood type, of human leukocyte antigen cross-match, or both. In KPD, the
      incompatibility problems with two donor recipient pairs can be solved by
      exchanging donors. In the absence of well-organized deceased donor program, or
      transplantation with desensitization protocol and ABO incompatible
      transplantation, living donor KPD promises hope to the growing number of patients
      suffering from end-stage renal disease in India. We report our first successful
      three-way KPD transplantation from India. In an era of organ shortage, this
      approach is relevant to encourage wider participation from KPD donors and
      transplant centers to prevent commercial transplantation. 

PMID- 24574633
TI  - Pregabalin-associated myoclonic encephalopathy without evidence of drug
      accumulation in a patient with acute renal failure.
AB  - Pregabalin, used for treating partial epilepsy and neuropathic pain, is usually
      well tolerated. Patients with impaired renal function are at risk to develop more
      serious adverse events. A 64-year-old woman was admitted in the Emergency
      Department for altered consciousness and abnormal movements. She recently started
      to take pregabalin (150 mg/day) for neuropathic pain. The drug was withdrawn 36 h
      before hospitalization following worsening of neurological symptoms. At physical
      examination, myoclonus was noted as main finding in the limbs and head, with
      encephalopathy. Laboratory investigations revealed acute renal failure with serum
      creatinine at 451.3 MUmol/l. Urine output was preserved. After supportive care
      alone, myoclonus resolved after 24 h and consciousness was normal after 48 h.
      Renal function was also recovered. At the time of admission, the concentration of
      plasma pregabalin was 3.42 MUg/ml, within therapeutic range. The calculated
      terminal elimination half-life was 11.5 h. Pregabalin-induced myoclonus may not
      be strictly related to drug accumulation in acute renal failure, with the
      possibility of a threshold phenomenon. 

PMID- 24574634
TI  - Intravenous albumin infusion is an effective therapy for hyponatremia in patient
      with malignant ascites.
AB  - There are few reports about the treatment of moderate to severe hyponatremia
      associated with malignant liver metastasis. Here, we report using intravenous
      salt poor albumin infusion to treat hypervolemic cirrhosis related hyponatremia.
      A 58-year-old female with ascites secondary to metastatic breast cancer was
      referred to our department with symptomatic hyponatremia (serum sodium
      concentration of 121 mEq/L). The serum sodium level was corrected slowly over 2
      days with intravenous albumin infusion and the patient's symptoms - fatigue,
      nausea, dizziness and headache improved. 

PMID- 24574635
TI  - A case of fatal disseminated Apophysomyces elegans infection in a renal allograft
      recipient.
AB  - An unusual fatal infection with Apophysomyces elegans belonging to the fungal
      class Zygomycetes in a renal transplant recipient is presented. 

PMID- 24574636
TI  - Membranous nephropathy superimposed on Churg-Strauss syndrome.
AB  - The association of membranous nephropathy with Churg-Strauss syndrome is not
      widely reported. We present a patient with myeloperioxidase-perinuclear
      antineutrophilic cytoplasmic antibody (MPO-pANCA)-positive necrotizing and
      crescentic glomerulonephritis who later developed membranous nephropathy. 

PMID- 24574637
TI  - Gitelman's syndrome: Rare presentation with growth retardation.
AB  - Gitelman's syndrome is an autosomal recessive disorder characterized by
      hypokalemic metabolic alkalosis, hypokalemia, hypomagnesaemia, hypocalciuria,
      hyperreninemia and without hypertension. Gitelman's syndrome is caused by
      mutations of the SLC12A3 gene, which encodes the Na/Cl co-transporter (NCCT) in
      the distal convoluted tubule. Majority of cases manifest during adolescence or
      adulthood and growth retardation is not the common feature. We report a rare
      presentation of Gitelman's syndrome in a four-year-old boy with growth
      retardation. 

PMID- 24574638
TI  - Looking beyond vesical calculi.

PMID- 24574639
TI  - The neutrophil lymphocyte ratio may be useful inflammatory indicator before
      applying other expensive and invasive procedures.

PMID- 24574640
TI  - Author's reply.

PMID- 24574641
TI  - Peritoneal dialysis in Peru.

PMID- 24574642
TI  - Utility of left-over renal tissue for light microscopy after immunofluorescence.

PMID- 24574643
TI  - Prevalence and risk factors of renal artery stenosis in South Asian patients with
      type 2 diabetes using renal angiography.

PMID- 24574644
TI  - From the Editor's desk.

PMID- 24574645
TI  - Collagenous spherulosis.

PMID- 24574646
TI  - Plasma fibrinogen degradation products in betel nut chewers - with and without
      oral submucous fibrosis.
AB  - CONTEXT: Oral submucous fibrosis (OSMF) has a multifactorial etiology. Recent
      studies have shown that there is an increased level of fibrinogen degradation
      products (FDP) in plasma of OSMF patients suggesting its possible role in
      etiopathogenesis of OSMF. AIMS: To detect the presence of FDP in the plasma of
      betel nut chewers with and without OSMF and in normal subjects without any
      habits, to correlate these levels with respect to the clinical and histological
      grading of OSMF and whether it can be used as a nonsurgical diagnostic aid in
      detection of suspected OSMF cases. MATERIALS AND METHODS: Study comprised of 35
      cases of betel nut chewers with OSMF, 10 patients with betel nut chewing habit
      but having apparently normal oral mucosa, and 10 normal patients without any
      habits. The patients were evaluated for plasma FDP levels. RESULTS: All the betel
      nut chewers with OSMF showed the presence of plasma FDP. However, controls and
      subjects with habit, but without OSMF did not show FDP in the plasma. Spearman's
      rank correlation was used to find the association between the clinical and
      histological grades and it was not statistically significant (P = 0.910) and the
      correlation being 0.020. CONCLUSION: Since only those patients with OSMF have
      showed the presence of FDP in plasma, we suggest that our test can be utilized as
      a nonsurgical diagnostic aid in suspected OSMF patients.

PMID- 24574647
TI  - Association between langerhans cells population and histological grade of oral
      squamous cell carcinoma.
AB  - CONTEXT: Langerhans cells (LCs) are a unique population of antigen processing
      cells in the epidermis and mucous membrane, which may play a role in the defence
      mechanism against epithelial tumors. AIMS: To compare the distribution of LCs in
      oral squamous cell carcinomas (OSCC) and normal oral epithelium; and to determine
      whether the population of LCs in OSCC has any correlation with histological
      grading of these malignancies. SETTINGS AND DESIGN: A cross-sectional
      immunohistochemical analysis of OSCC cases. MATERIALS AND METHODS: Forty-eight
      randomly selected paraffin tissue blocks of OSCC cases and 30 cases of normal
      oral epithelium were included. Hematoxylin and eosin-stained sections of the OSCC
      cases were reviewed and categorized as high-grade malignant tumors or low-grade
      malignant tumors. Tissue sections were analyzed for density of LCs using CD1a
      antibody expression. STATISTICAL ANALYSIS USED: Data are expressed as percentages
      compared by Chi-square statistics; mean +/- standard deviation, compared by Mann
      Whitney-U test and Spearman's correlation tests. RESULTS: LCs population was
      significantly higher in normal oral epithelium when compared with OSCC cases (P =
      0.001). There was also a significant difference in the number of LCs per
      millimetre square area of tissue section between well-differentiated tumors and
      poorly-differentiated tumours (P = 0.03). There was a negative correlation
      between the population density of LCs and the grade of OSCC. CONCLUSIONS: These
      findings suggest that oral mucosal LCs are involved in immune-surveillance and
      immunologic impairment may characterize invasive OSCC. In addition, LCs density
      characterizes histological grades of OSCC, which may be of a prognostic value.

PMID- 24574648
TI  - Histomorphometric analysis of vascularity in normal buccal mucosa, leukoplakia,
      and squamous cell carcinoma of buccal mucosa.
AB  - CONTEXT: Angiogenesis, the process that leads to the formation of new blood
      vessels, continues to be a topic of major scientific interest. There is an
      increasing hope that new discoveries will lead to newer therapies that target
      angiogenesis as a reliable option for disease therapy. AIMS: The objective of
      this study was to assess the role of vascularity, correlation of morphometric
      aspects of vascularity, investigate its usefulness in the histopathological
      classification and prognosis in normal buccal mucosa (NBM), leukoplakia and
      squamous cell carcinoma (SCC) of buccal mucosa. MATERIALS AND METHODS: The study
      sample consisted of 15 cases of NBM, 30 cases of leukoplakia, and 30 cases of SCC
      of buccal mucosa. The 75 archival samples were stained by hemotoxylin and eosin
      (H and E) and Masson's trichrome (MT). The stained sections were analyzed using
      image analysis software. STATISTICAL ANALYSIS USED: Statistical Package for
      Social Sciences (SPSS) 12.0 statistical software. RESULTS: The combined mean
      vessel density (MVD) of all the cases in H and E was 0.1112 and for MT it was
      0.2150. The difference of MVD between H and E and MT was statistically
      significant. The mean MVD in SCC (0.3455) for MT was higher than NBM (0.1314) and
      leukoplakia (0.1263). The mean MVD increased from stage III (0.3563) to IV
      (0.5312). It also increased from NBM (0.1314) to hyperkeratosis (0.1505) and
      decreased from grade I (0.3556) to II (0.2795) of oral SCC (OSCC). CONCLUSIONS:
      MVD can be used as an adjunct with other diagnostic modalities. Further studies
      are needed to standardize baseline levels for different sites and age groups.

PMID- 24574650
TI  - Comparative study on the microbiological features of angular cheilitis in HIV
      seropositive and HIV seronegative patients from South India.
AB  - OBJECTIVE: This study was designed to compare the microbiological features of
      angular cheilitis (AC) in human immunodeficiency virus (HIV) seropositive and HIV
      seronegative individuals, in a group of south Indians. MATERIALS AND METHODS:
      Swabs from oral commissures of 46 patients were obtained and inoculated on to
      Sabouraud's dextrose agar (SDA) supplemented with chloramphenicol, blood agar
      (BA) and MacConkey's agar (MCA) plates and cultured. alpha-hemolytic
      Streptococci, Staphylococcus albus, Staphylococcus aureus, Candida species,
      Klebsiella species and Pseudomonas species were cultured. Candidal colonies were
      further speciated by the conventional biotyping technique. RESULTS: In AC of HIV
      seropositive patients Candida albicans and Staphylococcus aureus were more
      prevalent than that in HIV seronegative patients. Incidentally in patients with
      CD4 cell count less than 200 there was an increase in the incidence of Candidal
      and Staphylococcus aureus colonization when compared to patients with CD4 cell
      count higher than 200. CONCLUSION: The present study suggests a definite
      difference in the microbial flora of AC in HIV seropositive patients than that of
      HIV seronegative population.

PMID- 24574649
TI  - Ca(2+)-deposition in cell matrix correlates significantly with osteocalcin
      expression in osteogenic differentiated ATSC: Even in a coculture system with
      HUVEC.
AB  - BACKGROUND: Tissue engineering offers the means for replacing or repairing
      diseased organs within the patient's body. The current problem in its clinical
      use is sufficient and fast revascularization of the transplanted tissues. The
      idea of bone-reconstruction deals with three-dimensional bone equivalents that
      are composed of endothelial cells (ECs) and adipose tissue derived stromal cells
      (ATSCs) showing osteogenic differentiation. MATERIALS AND METHODS: ATSC were
      isolated, cultivated until third passage and osteogenically differentiated by
      1.25-dihydroxycholecalciferol. Coculture systems with human umbilical vein
      endothelial cells (HUVEC) were performed. Osteogenic differentiation was analyzed
      in FACS-analyses (n = 7), by the measurement of Ca(2+)-deposition in the cell
      matrix (marker for osteogenic differentiation) and the expression of alkaline
      phosphatase (AP). RESULTS: Ca(2+)-deposition in the cell matrix and osteocalcin
      expression correlated significantly (P = 0.030) during osteogenic differentiation
      (n = 7). The osteogenic cell differentiated ATSC in the coculture system (n = 6)
      even showed a clear increase of Ca(2+)-deposition. The time of starting the
      coculture did not influence the differentiation. Measurement of the Ca(2+)
      deposition correlates significantly to the osteogenic differentiation and
      osteocalcin-expression. CONCLUSION: ATSC are a promising source for bone tissue
      engineering. They can be differentiated into osteoblasts in a coculture system
      with HUVEC without the loss of any differentiation capacity. For bone tissue
      equivalent fabrication, this is an encouraging procedure that is feasible and
      provides fast revascularization of the bone-equivalents.

PMID- 24574651
TI  - Cyclin D1 an early biomarker in oral carcinogenesis.
AB  - BACKGROUND: Dysregulation of cell cycle is a fundamental hallmark of cancer
      progression. Cyclin D1, part of complex molecular system regulating G1-S point of
      cell cycle is overexpressed in variety of tumors. AIMS: To look for its
      immunohistochemical expression in clinically normal mucosa from patients with and
      without tobacco habits, leukoplakia; and correlate its expression to individual
      atypical morphologic features, as seen in hematoxylin and eosin (H and E)
      sections of leukoplakia exhibiting dysplasia. MATERIALS AND METHODS: We examined
      the expression of cyclin D1 in immunohistochemically stained sections of 15
      normal buccal mucosa without any habits (group 1), 30 clinically normal mucosa
      from tobacco habituiotas (group 2) and 30 leukoplakias exhibiting dysplasias
      (group 3). Descriptive statistical analysis performed. Results presented on Mean
      +/- Standard deviation and in number (%). Adjusted Wald 95% Confidence Interval
      (CI) computed, percentages of morphological features assessed by Laplace
      estimate. Mann-Whitney U, Kruskal-Wallis test used to find the percentage
      expression of cyclin D1. RESULTS: Expression of cyclin D1 in group 3 was
      significantly higher than in group 1 and 2 (P < 0.001, P = 0.028), expression in
      group 2 was significantly higher than in group 1 (P = 0.003) and were
      statistically significant. Generally expression of cyclin D1 was confined to
      lower one-third of epithelium and was highest in mild dysplasias. Among 13
      atypical morphologic features, cyclin D1 expression consistently correlated with
      basilar hyperplasia. CONCLUSION: The altered pattern of cyclin D1 expression here
      may be an early event in conversion of normal epithelium into dysplastic
      epithelium and may serve as a biomarker of oral carcinogenesis. Its expression
      may be increased in tobacco habitues. Basilar hyperplasia should be given
      additional weightage in the grading system in predicting the fate of affected
      epithelium.

PMID- 24574652
TI  - Immunohistochemical expression of Src protein in peripheral and central giant
      cell granulomas of the jaws.
AB  - AIM AND OBJECTIVE: The aim of this study was to investigate the expression of Src
      protein (an osteoclastic factor) in peripheral and central giant cell granulomas
      (PGCG and CGCGs) of the jaws and the relationship between the expression of this
      protein and the clinical behavior of these two lesions. MATERIALS AND METHODS:
      Thirty cases of PGCG and 30 cases of CGCG were immunohistochemically stained with
      Src. A staining-intensity-distribution (SID) score (proportion of stained cells *
      staining intensity) was used to evaluate immunoreactivity of the protein. Data
      were analyzed using statistical package for social sciences (SPSS) 17.0. RESULTS:
      There were no significant differences in the Src expression and the SID score
      between PGCG and CGCG. Furthermore, Spearman's rank correlation coefficient
      showed that there was a significant correlation between Src expression and SID
      score within both PGCG and CGCG (P < 0.001; r = 0.87 and 0.75, respectively).
      CONCLUSION: The findings of this study suggest that the multinucleated giant
      cells share some similarities with osteoclasts and Src protein can be used as a
      new therapeutic target to inhibit osteoclastic activity. In addition, differences
      in immunoreactivity of this osteoclastic protein do not reflect different
      clinical behaviors of PGCG and CGCG.

PMID- 24574653
TI  - Biosafe alternative to xylene: A comparative study.
AB  - BACKGROUND: Xylene in one of the non-substitutable chemical used in histology
      laboratories. However, it is known to have many toxic effects. The toxic effects
      of xylene include heart and kidney injuries, some fatal blood dyscrasia and other
      less dangerous problems, such as skin erythema, drying, scaling and secondary
      infections. The exposure and handling of xylene is maximum during deparaffinizing
      tissue sections. AIMS: The aim of this study was to evaluate the efficacy of 1.7%
      dishwashing soap (DWS) solution as a deparaffinizing agent for hematoxylin and
      eosin (H and E) staining and compare it with xylene. MATERIALS AND METHODS: Sixty
      sections of 4 MUm were obtained from 30 formalin-fixed paraffin-embedded (FFPE)
      tissues and were considered in two different groups, groups A and B. Slides in
      group A were stained with routine H and E staining procedure; whereas, slides in
      group B were stained using 1.7% DWS as a deparaffinizing agent. STATISTICAL
      ANALYSIS USED: Wilcoxon matched-pairs signed rank test was used to calculate the
      test of significance (P-value significant at <=0.05). RESULTS AND CONCLUSION:
      1.7% DWS was found to be an effective alternative deparaffinizing agent to xylene
      and meanwhile facilitating as less biohazardous, economical and a faster
      deparaffinizing agent.

PMID- 24574654
TI  - VEGF and CD 34: A correlation between tumor angiogenesis and microvessel density
      an immunohistochemical study.
AB  - BACKGROUND: Angiogenesis is the formation of new vessels from preexisting ones
      which takes place by capillary sprouting. It is seen in healing, at sites of
      injury and collateral circulation in ischemia. It is also seen in tumors, as once
      the original blood supply of a tumor is exhausted it cannot grow without further
      blood supply. Also as the angiogenic capacity of a tumor increases, its
      microvasculature, that is, microvessel density (MVD) also increases. Based on
      this literary evidence we carried out an immunohistochemical (IHC) study to
      observe the relationship between the expression of vascular endothelial growth
      factor (VEGF) [angiogenesis] and CD 34 [MVD] in oral squamous cell carcinoma
      (OSCC). AIM: To evaluate the correlation between expression of VEGF and CD 34,
      the role of MVD in progression of OSCC and to compare the degree of angiogenesis
      in different grades of OSCC. SETTINGS AND DESIGN: In this study we observed the
      relation between angiogenesis and MVD and the overall effect of this on oral
      cancer. MATERIALS AND METHODS: Thirty-three cases of OSCC were stained with
      hematoxylin and eosin, (H and E) to confirm the diagnosis and
      immunohistochemically using VEGF and CD 34 antibody. The slides were evaluated
      for positivity and intensity of staining. STATISTICAL ANALYSIS: The result was
      subjected to statistical analysis using analysis of variance (ANOVA) test and
      Fisher's exact test. RESULTS: VEGF positivity as well as MVD was found to be
      independent of the grade of the tumor. Tumor MVD was found to be independent of
      expression of VEGF.

PMID- 24574655
TI  - Detection of micrometastasis in lymph nodes of oral squamous cell carcinoma: A
      comparative study.
AB  - BACKGROUND: The annual mortality rate from head and neck squamous cell carcinoma
      (HNSCC) is over 11,000 worldwide. Squamous cell carcinoma of the head and neck
      (SCCHN) frequently metastasizes to the regional lymph nodes which are the first
      site of arrest of tumor cells that have invaded the peritumoral lymphatics, hence
      the strongest predictor of disease prognosis and outcome. AIM: The present study
      aims to compare the efficacy of frozen sections (cryosection), step-serial
      sectioning conventional H and E staining, immunohistochemistry (IHC) and RT-PCR
      analysis in detection of lymph node micrometastasis. MATERIALS AND METHODS: A
      prospective series of 30 patients who were diagnosed with primary squamous cell
      carcinoma of the oral cavity and underwent surgical treatment including
      unilateral or bilateral selective neck dissection were considered for the study.
      RESULT: Metastatic carcinomatous cells were observed in H and E staining of
      frozen section in 18 lymph nodes (54%) and in 19 lymph nodes (57%) in step-serial
      sectioned H and E-stained sections of the 78 lymph nodes from 30 patients.
      Carcinomatous cells were immunolabeled with pancytokeratin in 18 lymphnodes
      (54%). CK19 mRNA was detected in 33 lymph nodes of 16 patients. RT-PCR gave
      positive signals for 24% and 23% of lymph nodes positive by histopathology and
      immunohistochemistry. CONCLUSION: Our study demonstrated that RT-PCR is far more
      sensitive in detection of micrometastasis than any other technique used in
      routine procedures and immunohistochemistry. Fifty-three percent patients with
      micrometastasis detected by RT-PCR had large T3/T4 tumors. Prognosis was poor for
      patients who were positive for micrometastasis detected only by RT-PCR, among
      which two patients died within a period of 6 months.

PMID- 24574656
TI  - Estimation and correlative study of salivary nitrate and nitrite in tobacco
      related oral squamous carcinoma and submucous fibrosis.
AB  - Oral cancer is one of the ten leading cancers of the world. In India, it is one
      of the common cancers and is an important public health problem. Tobacco plays
      significant role in etiology of oral squamous carcinoma. Tobacco which is chewed
      or smoked contains many alkaloids which are known carcinogens. Oral submucous
      fibrosis (OSMF) is a disease of the Indian subcontinent, which through
      immigration has a worldwide distribution. Betel nut chewing plays significant
      role in etiology of OSMF. The nut alkaloids have been shown experimentally to
      result in stimulation of collagen synthesis by fibroblasts in vitro, which can
      induce precancerous conditions. MATERIALS AND METHODS: The present study was
      undertaken to detect nitrate and nitrite factor in saliva of cases with oral
      carcinoma, OSMF and normal individuals without any habits and to determine
      whether increased salivary nitrate and nitrite level is significant in oral
      carcinoma and submucous fibrosis using biochemical parameters. CONCLUSION: We
      conclude that the major inducer of oral squamous cell carcinoma (OSCC) is
      exposure to tobacco. Recent studies have demonstrated that oxidative and
      nitrosative stress contributes to the development of oral carcinogenesis through
      deoxyribonucleic acid (DNA) damage. Salivary composition of OSCC patients is
      substantially altered with respect to free radical-involved mechanisms.

PMID- 24574657
TI  - Comparison of routine decalcification methods with microwave decalcification of
      bone and teeth.
AB  - INTRODUCTION: The microwave oven has been used quite often for tissue processing,
      but there are very few studies describing its use in decalcification of bone or
      teeth. In this study we have attempted to decalcify bone and teeth using a
      microwave oven and compare the process and results with conventional
      decalcification methods. AIMS AND OBJECTIVES: The objectives of the study were to
      determine and compare routine decalcification with microwave decalcification of
      bone and teeth using 5% nitric acid, 5% formic acid, and 14%
      ethylenediaminetetraacetic acid (EDTA) with respect to speed of decalcification,
      preservation of tissue structure and staining efficacy. MATERIALS AND METHODS: In
      our study the total sample size used for both routine and microwave
      decalcification was 30 premolar teeth and 30 pieces of condyles. The three
      solutions were dilute nitric acid (5%), formic acid (5%), and EDTA (14%). Each
      set consisting of the same type of premolars and condyles in each of the three
      decalcifying solutions were used in both manual method and microwave method.
      RESULTS: The results in the present study confirmed the fact that the microwave
      method using nitric acid was indeed the fastest decalcifying method needing just
      about 2 days for condyle and 4 days for premolars, compared with routine
      decalcification. The results also showed that the overall histological picture
      was good with EDTA and formic acid irrespective of the methods used. In the
      routine method, nitric acid gave poor cellular detail when compared with
      microwave method. CONCLUSION: With our study we conclude that microwave oven
      decalcification is faster than routine decalcification irrespective of the
      decalcifying agents used. The tissue preservation and staining efficacy was good
      in microwave nitric acid decalcification compared to routine nitric acid
      decalcification. Both formic acid and EDTA show good tissue preservation and
      staining efficacy irrespective of the method used.

PMID- 24574658
TI  - Verruciform xanthoma: A view on the concepts of its etiopathogenesis.
AB  - Verruciform xanthoma is a very uncommon papillary growth seen chiefly in the oral
      mucosa. The presence of foam cells in the connective tissue papillae between the
      epithelial rete ridges forms the hallmark in its diagnosis. There has been wide
      speculation and various hypotheses put forth in explaining the etiopathogenesis
      of verruciform xanthoma and the origin of foam cells. This article aims to update
      the different hypotheses in understanding the pathogenesis of the lesion. 

PMID- 24574659
TI  - Facts in artifacts.
AB  - Examination of microscopic sections of animal tissues reveals facts which are not
      always related to its normal histology or pathology. Processing of tissue
      specimens consists of lengthy procedures from the stage of surgical removal to
      the stained and mounted microscopic sections. Defects are common in tissue
      sections as a result of faulty procedures. These defects are referred to as
      artifacts. They lead to misinterpretation of histopathological diagnosis but at
      times they throw limelight into diagnosis. This paper attempts to put together
      all the facts regarding the various artifacts that are encountered in
      histopathology. 

PMID- 24574660
TI  - Quality and safety aspects in histopathology laboratory.
AB  - Histopathology is an art of analyzing and interpreting the shapes, sizes and
      architectural patterns of cells and tissues within a given specific clinical
      background and a science by which the image is placed in the context of knowledge
      of pathobiology, to arrive at an accurate diagnosis. To function effectively and
      safely, all the procedures and activities of histopathology laboratory should be
      evaluated and monitored accurately. In histopathology laboratory, the concept of
      quality control is applicable to pre-analytical, analytical and post-analytical
      activities. Ensuring safety of working personnel as well as environment is also
      highly important. Safety issues that may come up in a histopathology lab are
      primarily those related to potentially hazardous chemicals, biohazardous
      materials, accidents linked to the equipment and instrumentation employed and
      general risks from electrical and fire hazards. This article discusses quality
      management system which can ensure quality performance in histopathology
      laboratory. The hazards in pathology laboratories and practical safety measures
      aimed at controlling the dangers are also discussed with the objective of
      promoting safety consciousness and the practice of laboratory safety. 

PMID- 24574661
TI  - Pathophysiology of merkel cell.
AB  - The objective of this review is to introduce Merkel cells (MCs), to provide a
      basic overview on the theoretical background of function, development and
      clinical importance of MCs. The origin of human MCs have been controversial. Some
      investigators believe that it is a neural crest derivate, whereas others have
      proposed that it is a differentiation product of the fetal epidermal
      keratinocytes. MCs are cells primarily localized in the epidermal basal layer of
      vertebrates and concentrated in touch-sensitive areas in glabrous, hairy skin and
      in some mucosa. In routine light microscopy, human MCs can hardly be identified.
      Cytokeratin 20 (CK20) is a reliable marker with highest degree of specificity.
      MCs can be also distinguished by electron microscopy. MC carcinoma (MCC) is an
      uncommon and often aggressive malignancy and found mainly in elderly patients. It
      occurs most frequently in the head and neck region. Diagnosis is based on typical
      histological presentation on hematoxylin and eosin (H and E) stained slides
      together with the results of immunohistochemistry. Histologically, MCC has been
      classified into three distinct subtypes: Trabecular, intermediate and small cell
      type. 

PMID- 24574662
TI  - Primary oral myeloid sarcoma: Report of a case.
AB  - Myeloid sarcoma is defined as a tumor mass of immature myeloid cells that may be
      observed in a variety of locations including bone, skin, lymph nodes and soft
      tissues. However, oral involvement of myeloid sarcoma is extremely rare. These
      tumors are considered as specific lesions of acute myeloid leukemia. We present a
      case of a myeloid sarcoma of the upper vestibular gingiva in a 29-year-old woman
      who has no hematologic disease history. Multiple metastases were found in floor
      of the nasal cavity, left breast, and left lacrimal gland 12 months after primary
      diagnosis. 

PMID- 24574663
TI  - Plasma cell myeloma infiltrating the dental pulp: An interesting finding.
AB  - Plasma cell myeloma (PCM) is a clonal neoplastic proliferation of terminally
      differentiated B lymphocytes (plasma cells/myeloma cells) that involves the
      skeletal system in a multifocal fashion. Even though jaw involvement has been
      reported in as many as 30% of cases, myeloma cells infiltrating into the pulpal
      tissue is extremely rare. Here, we present a case of PCM in which myeloma cells
      are seen infiltrating into the pulpal tissue of 46. 

PMID- 24574664
TI  - Granuloma with langhans giant cells: An overview.
AB  - Granuloma formation with multinucleated giant cells is seen in numerous diseases.
      A granuloma is a focus of chronic inflammation consisting of a microscopic
      aggregation of macrophages surrounded by a collar of lymphocytes and plasma
      cells. In this article, we present a case of granuloma formation with multiple
      Langhans giant cells along with an overview of the differential diagnoses, which
      include mycobacterium diseases, other bacterial infections, fungal infections,
      protozoal infections, and other granulomatous diseases. 

PMID- 24574665
TI  - Ameloblastic fibrosarcoma: Report of a case.
AB  - Ameloblastic fibrosarcoma (AFS) is a rare odontogenic malignancy with benign
      epithelial and malignant ectomesenchymal components. About 66 cases have been
      reported in the medical literature. We therefore report an additional case as
      well as a review of literature to add to the existing knowledge on this rare
      lesion. 

PMID- 24574666
TI  - Myoepithelial carcinoma arising in recurrent pleomorphic adenoma in maxillary
      sinus.
AB  - Myoepithelial carcinoma is characterized by nearly exclusive myoepithelial
      differentiation and evidence of malignancy. It may arise de novo or in
      preexisting benign tumors including pleomorphic adenoma and benign
      myoepithelioma. A 39-year-old lady presented with painless progressive swelling
      on the right cheek and right side of palate. On surgery, there was a mass in
      right maxillary sinus which was surgically excised and diagnosed on
      histopathology as pleomorphic adenoma. Subsequently, there were two recurrences.
      The first recurrence was in the right maxilla after 2 years that was removed
      surgically and diagnosed as pleomorphic adenoma. One year later, she came with
      rapidly progressive swelling in bilateral cheeks and face. Intraoperatively,
      there was a large tumor in both maxillary sinuses with extensive local
      infiltration. Histologically, it was diagnosed as myoepithelial carcinoma.
      Carcinoma ex pleomorphic adenoma is usually a high grade malignancy. It occurs
      most commonly in parotid gland followed by submandibular glands, minor salivary
      glands and occasionally in sublingual gland. To the best of our knowledge, this
      is the first case of myoepithelial carcinoma arising in a recurrent pleomorphic
      adenoma in the maxillary sinus. 

PMID- 24574667
TI  - Oral lesions associated with Nevirapine-induced Stevens-Johnson syndrome and
      toxic epidermal necrolysis: A report of 10 cases.
AB  - Stevens-Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN) are closely
      related severe, acute mucocutaneous reactions usually caused by drugs. They are
      acute life-threatening conditions and cause widespread necrosis of the
      epithelium. There is persistence of a high risk of SJS or TEN in relation to
      human immunodeficiency virus (HIV) infection associated with exposure to
      nevirapine (NVP). In this article, we present nine cases of SJS and one case of
      TEN in HIV-seropositive individuals who developed cutaneous, oral, ocular and
      genital lesions while being treated with NVP. 

PMID- 24574669
TI  - Congenital granular cell lesion: A rare tumor of new born.
AB  - Congenital granular cell tumor (CGCT), or congenital epulis, is an uncommon
      benign soft tissue lesion that usually arises from the alveolar mucosa of
      neonates and may cause respiratory and feeding problems. The histogenesis and
      clinical history of the lesion remains obscure. Treatment involves surgical
      excision and recurrences are rare. The present report describes a case of
      congenital granular cell lesion (CGCL) in the anterior segment of maxillary
      alveolar ridge of a 2-month-old female. This lesion was causing feeding problem
      and was excised under local anesthesia, with no recurrence even after 3 years. 

PMID- 24574668
TI  - Atypical case of primary intraosseous adenoid cystic carcinoma of mandible.
AB  - The Primary central salivary gland neoplasms of the mandible are infrequent.
      Their clinical and radiographic features may be similar to odontogenic tumors,
      which are otherwise common. Their accurate diagnosis becomes troublesome. Hence,
      diagnosis should depend on stringent diagnostic criteria. Adenoid cystic
      carcinoma is well known for its prolonged clinical course and its tendency for
      delayed onset of distant metastases. The long-term survival of these patients is
      therefore poor. Treatment modalities include surgery, radiotherapy and
      chemotherapy. The purpose of this paper is to report a case of primary central
      adenoid cystic carcinoma of mandible with an atypical presentation. 

PMID- 24574670
TI  - Diagnosis and management of bilateral nasolabial cysts.
AB  - Nasolabial cysts are painless, submucosal, non-odontogenic jaw cysts presenting
      as soft tissue swellings in the maxillary anterior mucolabial fold lateral to
      midline, leading to elevation of nasal ala. Present case documents bilateral
      nasolabial cysts in a 69-year-old Asian female patient. In the present case,
      extraoral swelling of maxillary lip and elevation of nasal ala was observed on
      right side of the face. Intraorally, soft and fluctuant bilateral cysts were
      observed. Straw-colored fluid was aspirated from the right cyst.
      Radiographically, erosion of bone in a "cupping" fashion was observed in the
      region of left cyst. The cysts were enucleated using intraoral approach.
      Histopathology of the right-sided cyst revealed a cystic cavity lined by
      stratified squamous cells along with a few mucosal cells. At few places,
      stratified squamous and pseudostratified columnar epithelia with many cilia and
      goblet cells were also evident. Capsule was loosely arranged with fibrous tissue
      and chronic inflammatory infiltrate. Left-sided cystic specimen showed two or
      more layered stratified squamous lining epithelium with thin capsule. Diagnosis
      of bilateral nasolabial/nasoalveolar cysts was confirmed. 

PMID- 24574671
TI  - Ancient neurilemmoma: A rare oral tumor.
AB  - Neurilemmomas are benign tumors of neural origin composed of Schwann cell
      proliferation in characteristic patterns. Ancient neurilemmomas are usually
      longstanding growths that exhibit degenerative features that could be mistaken
      for malignancy. They are extremely rare in the oral cavity and present in older
      individuals of long duration. The authors report a case of ancient neurilemmoma
      in a young patient with short duration of growth. This unique case presented with
      remarkable histopathological features with respect to vascularity and atypia
      associated with degenerative change. It is essential to not mistake these
      features as malignant transformation so as to avoid radical procedures. 

PMID- 24574672
TI  - Achondroplasia with oligodontia: Report of a rare case.
AB  - Achondroplasia is considered as a form of skeletal dysplasia/dwarfism that
      manifests with stunted stature and disproportionate limb shortening.
      Achondroplasia is of special interest in the field of dentistry because of its
      characteristic craniofacial features. It has been considered as the most common
      short-limbed dwarfism syndrome. Very few authors have reported the presence of
      oligodontia in achondroplastic patients. The present paper reports a rare case of
      oligodontia in a young, female, achondroplastic patient. 

PMID- 24574673
TI  - Kimura's disease - An unusual presentation involving subcutaneous tissue, parotid
      gland and lymph node.
AB  - Kimura's disease is a rare chronic inflammatory condition of uncertain etiology
      which has an affinity for the Asian population. It primarily involves the head
      and neck region, presenting as deep subcutaneous masses and is often accompanied
      by regional lymphadenopathy and salivary gland involvement. Peripheral blood
      eosinophilia and elevated serum immunoglobulin E (IgE) levels are characteristic
      features and the microscopic picture reveals lymphoid proliferation with
      eosinophilic infiltration. For years, Kimura's disease was believed to be
      identical to or part of the same disease spectrum as angiolymphoid hyperplasia
      with eosinophilia (ALHE). Recent reports, however, have confirmed that the two
      are, in fact, separate entities. We report a case of Kimura's disease in a 22
      year-old Indian male who presented with a subcutaneous mass, parotid enlargement
      and lymphadenopathy. The clinical presentation was suggestive of Kimura's disease
      and microscopic examination following biopsy of the lesion allowed us to make a
      definitive diagnosis. 

PMID- 24574674
TI  - Bisphosphonate-induced osteoradionecrosis.
AB  - Bisphosphonates (BPs) are a class of agents used to treat osteoporosis and
      malignant bone metastasis. Despite these benefits, osteonecrosis of the jaws has
      recently emerged as a significant complication in a subset of patients receiving
      these drugs. This case presentation focuses on a 62-year-old man with a 3-year
      history of monthly use of Zometa (zolendronic acid) for treatment of multiple
      myeloma, resulting in BP-related osteoradionecrosis of the jaws (BRONJ). This new
      entity remains a challenge with diagnosis as well as treatment. The goal of this
      paper is to improve clinicians understanding and provide a guideline for
      establishing a stage-specific diagnosis and prevention of BRONJ. 

PMID- 24574675
TI  - Idiopathic huge pyogenic granuloma in young and old: An unusually large lesion in
      two cases.
AB  - Pyogenic granuloma (PG) is a reactive hyperplasia of connective tissue in
      response to local irritants, chronic irritation and hormonal changes. It is a
      tumor-like growth of the oral cavity frequently located in the region surrounding
      the anterior teeth or skin. It usually arises in response to various stimuli,
      such as low-grade local irritation, traumatic injury, hormonal factors or certain
      kinds of drugs. Clinically, the lesion appears as a smooth, lobulated, exophytic
      mass, exhibiting pink to reddish-purple color which can bleed on slight
      manipulation. PG has no malignant potential, but recurrence is common after
      surgical excision. Histologically, the surface epithelium may be intact and may
      show foci of ulcerations or exhibit hyperkeratosis. Gingiva is the most common
      site affected followed by buccal mucosa, tongue and lips. The size of lesion
      varies from millimeters to several centimeters; rarely exceeding 2-2.5 cm. PG
      larger than 2.5 cm are seldom reported. Estrogen has been considered as a major
      contributing factor in most of the cases. Thus, occurrence of PG is mostly seen
      in premenopausal age due to high levels of estrogen. In this article, two
      unusually large oral PG have been reported. In the first case, a 25-year-old
      young male patient and in the second case, 70-year-old female patient have been
      described. In both the cases, the size of lesion was more than 5 cm which has
      been rarely reported before. Also one of the cases describe here is of a
      postmenopausal female, which questions role of estrogen as an etiological factor.

PMID- 24574676
TI  - Anterior maxillary metastasis of gastric adenocarcinoma: A rare case.
AB  - Metastatic tumors of the oral cavity are rare, representing about 1% of oral
      tumors. Seventy percent of all tumors metastatic to the oral and maxillofacial
      region are adenocarcinomas, most commonly originating from the breast, kidney and
      lung. Carcinoma of stomach is generally described as one of the "captains of men
      of death". Usual sites of metastasis from gastric adenocarcinoma are direct
      invasion of adjacent organs, peritoneal dissemination, lymphatic metastasis and
      hematogenous spread. A primary carcinoma of the stomach may rarely metastasize to
      the oral cavity, it is important to bear this possibility in mind because such
      conditions may mimic a benign disease. This article describes a case of
      metastasis of gastric adenocarcinoma to the maxilla in a 50-year-old male. 

PMID- 24574677
TI  - Cheilitis granulomatosa.

PMID- 24574678
TI  - Dedifferentiation in adenoid cystic carcinoma.

PMID- 24574679
TI  - Primary fibrosarcoma of maxilla in an 8-year-old child: A rare entity.
AB  - Fibrosarcoma (FS) is a malignant mesenchymal neoplasm of the fibroblasts that is
      uncommon in the head and neck and constitutes less than 1% of malignancies and
      approximately 6% of the soft tissue sarcomas. FSs rarely occur before the third
      decade except infantile type. This condition primarily affects long bones, and
      its occurrence in the cranium is rare (15%), with the mandible being the most
      commonly involved cranial site. Here a case of primary FS in anterior maxilla of
      an 8-year-old male child is reported. This article is presented to document the
      rarity of FSs in the jaws of children with review of literature. 

PMID- 24574680
TI  - Taurodontism: A dental rarity.
AB  - Taurodontism is a developmental disturbance of a tooth in which body is enlarged
      at the expense of the roots. An enlarged pulp chamber, apical displacement of the
      pulpal floor and lack of constriction at the cementoenamel junction are the
      characteristic features. It appears most frequently as an isolated anomaly. But
      its association with several syndromes and abnormalities has also been reported.
      Endodontic treatment of taurodont teeth is stated to be complex and difficult due
      to the complexity in the tooth morphology. This case report presents a case of
      taurodontism in permanent maxillary molars and their successful endodontic
      treatment. 

PMID- 24574681
TI  - Clear cell variant of calcifying epithelial odontogenic tumor of maxilla: Report
      of a rare case.
AB  - The calcifying epithelial odontogenic tumor (CEOT) is a rare benign tumor of the
      jaws. Pindborg's tumor having clear cells is extremely rare. Twelve central
      lesions have been reported of which only three cases have occurred in maxilla.
      Clear cell variant is a distinct entity, has more aggressive biological behavior
      and higher chances of recurrence. Hence it is important that presence of clear
      cells be included in histopathological diagnosis. Here we present a rare case of
      clear cell CEOT having aggressive behavior. 

PMID- 24574682
TI  - Three kinds of cysts in the same patient.
AB  - An 18-year-old male patient presented with a swelling in the neck with
      presumptive diagnosis of epidermal cyst (EC) that was enucleated,
      histopathological examination confirmed the diagnosis. Four years later the
      patient presented with another swelling with similar clinical features. It was
      located on the midline of the neck at the hyoid bone. Excision of cyst was done
      and microscopically it showed features of thyroglossal duct cyst (TDC). Two
      months later a new swelling was noted on the right side of the neck. A complete
      surgical excision was done and the lesion was diagnosed as a lymphoepithelial
      cyst. The purpose of this report was to analyze each of the entities that were
      present in this case; since, the presence of three different cervical cystic
      lesions in the same patient is uncommon. 

PMID- 24574683
TI  - Orthokeratinizing odontogenic cyst of maxilla with complex odontoma.
AB  - The orthokeratinized odontogenic cyst (OOC) and odontoma are the odontogenic cyst
      and tumor respectively that are minimally invasive neoplasms of head and neck
      region. OOC is a rare variant of odontogenic cyst characterized by the presence
      of excessive orthokeratin covering the cystic lining. Odontoma is a benign
      neoplasm/hamartoma often discovered accidently on panoramic radiographs. We came
      across a case of a 26-year-old male with swelling on his face along with
      difficulty in breathing. On the basis of radiographic and histopathological
      findings the final diagnosis of OOC associated with odontoma was given. However,
      there is no report in the English literature of the simultaneous occurrence of
      these two lesions and hence this case is very rare. It is unclear whether the two
      lesions were just coincidental or were actually related to each other. 

PMID- 24574684
TI  - Cysticercosis of tongue: Cytohistologic approach to diagnosis.
AB  - Cysticercosis is continuing to be a major health problem in developing countries.
      Radiological and serological techniques are routinely used for pre-operative
      diagnosis of cysticercosis. But fine needle aspiration cytology (FNAC) is cost
      effective and simple procedure, so it is important to be aware of diagnostic
      pitfalls in the cytomorphologic diagnosis of cysticercosis. We present a case of
      cysticercosis of tongue, which accounts for only 34 cases in the world
      literature. 

PMID- 24574685
TI  - Receptors in trichology: hot spots for hair regeneration.

PMID- 24574686
TI  - The difficult hair loss patient: a particular challenge.
AB  - Few dermatologic complaints carry as much emotional overtones as hair loss.
      Adding to the patient's worry may be prior frustrating experiences with
      physicians, who trivialize hair loss. A detailed patient history, physical
      examination and few pertinent screening blood tests usually establish a specific
      diagnosis. Once the diagnosis is certain, treatment appropriate for that
      diagnosis is likely to control the problem. Treatment options are available,
      though limited, in terms of indications and efficacy. Success depends both on
      comprehensions of the underlying pathology and on unpatronizing sympathy from the
      part of the physician. Ultimately, patients need to be educated about the basics
      of the hair cycle and why considerable patience is required for effective
      cosmetic recovery. Communication is an important component of patient care. For a
      successful encounter at an office visit, one needs to be sure that the patient's
      key concerns have been addressed. Physicians should recognize that alopecia goes
      well beyond the simple physical aspects of hair loss. Patients' psychological
      reactions to hair loss are less related to physicians' ratings than to patients'
      own perceptions. Some of the patients have difficulties adjusting to hair loss.
      The best way to alleviate the emotional distress is to eliminate the hair disease
      that is causing it. Treatment success relies on patient compliance. Rather than
      being the patient's failure, patient non-compliance results from failure of the
      physician to ensure confidence and motivation. Finally, patients with
      hypochondriacal, body dysmorphic, somatoform, or personality disorders remain
      difficult to manage. The physician should be careful not to be judgmental or
      scolding because this may rapidly close down communication. The influence of the
      prescribing physician should be kept in mind, since inspiring confidence versus
      scepticism and fear clearly impacts the outcome of treatment. Sometimes the
      patient gains therapeutic benefit just from venting concerns in a safe
      environment with a caring physician. 

PMID- 24574687
TI  - Proliferating trichilemmal cyst: the value of ki67 immunostaining.
AB  - BACKGROUND: A proliferating trichilemmal cyst (PTC) is an uncommon, rapidly
      reproducing cutaneous epithelial cyst, differentiating from the isthmic portion
      of the outer hair root sheath. It is usually described as a benign tumor, but
      malignant transformation has been reported and is then denominated as a malignant
      proliferating trichilemmal tumor. Ki67 immunostaining has been used as a
      methodology for the evaluation of tumor grade in other tumors, due to its
      distinctive reaction patterns which exclusively involve proliferating cells.
      OBJECTIVES: (1) To report the incidence of cases of PTCs in a General Hospital
      during a 12 years period. (2) To determine the expression of ki67 using
      immunohistochemical staining. (3) To correlate ki67 reaction patterns with
      clinical prognosis. MATERIALS AND METHODS: The dermatology department's files
      during a period of 12 years were reviewed; cases with a diagnosis of PTC were
      selected, and ki67 immunostaining was done when enough biological material was
      available. RESULTS: A total of 15 cases with a diagnosis of PTC were identified.
      In 12 cases, ki67 immunostaining was carried out. In 9 of the 12 cases, ki67 was
      observed in the basal cells of the cystic epithelium, one case was moderately
      positive in palisading epithelial cells; in the other two cases ki67
      immunostaining was negative. Clinical follow-up was done and revealed that no
      patient had local recurrence in 5 years after surgical removal of PTC. We
      therefore consider this immunostaining technique is probably correlated with low
      recurrence potential.

PMID- 24574688
TI  - Vellus hairs in the frontal scalp in early female pattern hair loss.
AB  - BACKGROUND: Dermoscopy of the scalp (trichoscopy) is a technique to evaluate the
      skin of the scalp and the hair disorders. It clinically helps to establish early
      female pattern hair loss (FPHL) without the need for more invasive techniques.
      OBJECTIVES: This work intends to demonstrate new adjunct criteria for the
      clinical diagnosis of FPHL by determining the number of short vellus hairs
      encountered in the frontal area of the scalp of female patients with FPHL.
      MATERIALS AND METHODS: We retrospectively reviewed the trichoscopy images from 45
      women affected by FPHL in initial stages, at 20 fold magnification dermoscopy at
      2 cm from the hairline into the frontal area of the scalp. RESULTS: A total of 45
      patients images included had more than 20% variability at dermoscopy, criteria
      utilized to diagnose and included them in the study. All patients were graded as
      Ludwig I severity, 14 patients had frontal accentuation. The average number of
      vellus hairs in the frontal area at 20-fold magnification of all patients was of
      12.02 vellus hair in the frontal area. When comparing the Ludwid I pattern group
      versus the Ludwig I with frontal accentuation pattern group there was no
      statistical difference between the two clinical groups. CONCLUSIONS: All 45
      patients analyzed in this study were clinically diagnosed with FPHL. The number
      of vellus hairs in the frontal area was greater than the average found in normal
      subjects. Most patients (80%) with FPHL had more than or equal to seven vellus
      hairs per 20-fold magnification field in the frontal area, therefore we suggest
      that the presence of more than 6 vellus hairs in the frontal scalp at 20-fold
      magnification can be used as an additional criterion of FPHL.

PMID- 24574689
TI  - Is trichoscopy a reliable tool to diagnose early female pattern hair loss?
AB  - BACKGROUND: Female pattern hair loss (FPHL) presents with visible patterns of
      hair loss, thus making a bedside diagnosis possible. However, there are cases of
      FPHL presenting without any visible hair thinning, making it necessary to subject
      them to a scalp biopsy to make a diagnosis. AIM: The aim of the following study
      is to determine if trichoscopy can be used as a bedside tool to diagnose Early
      FPHL in women presenting without any visible thinning of hair, using >20% hair
      diameter diversity - anisotrichosis, as the diagnostic criteria. MATERIALS AND
      METHODS: Trichoscopy was performed on 20 cases of early FPHL (biopsy proven), 63
      normal controls and 29 Grade 2 FPHL Controls. RESULTS AND DISCUSSION: In the
      biopsy proven FPHL cases, 75% showed anisotrichosis on trichoscopy. This finding
      was significantly higher in FPHL Cases compared to normal controls. As expected,
      93% of Grade 2 FPHL controls also showed the same finding. Trichoscopy was found
      to be 75% sensitive and 61.54% specific in diagnosing early FPHL. Thus, a
      negative result would be more indicative of absence of disease, however, a
      positive result would not always indicate the presence of disease.

PMID- 24574690
TI  - Application of the basic and specific classification on patterned hair loss in
      indians.
AB  - CONTEXT: Several classifications for pattern hair loss (PHL) have been used over
      the years. The Norwood-Hamilton classification for men and Ludwig's
      classification for women is used commonly, but they have their limitations. AIMS:
      The objective of the following study is to evaluate the efficacy of the basic and
      specific (BASP) classification in Indian populations. SUBJECTS AND METHODS: We
      used the BASP classification to classify the PHL in the patients visiting our out
      patient department in the period from June 2012 to May 2013. 763 patients were
      classified out of which 313 were females and 450 were males. RESULTS: The
      majority of the female patients were in the 3-5(th) decade of life and in males
      were in 4-6(th) decade. CONCLUSIONS: The BASP classification is, easily
      remembered, reproducible classification for the diagnosis and treatment for both
      male and female pattern alopecia.

PMID- 24574691
TI  - Clinical and dermatoscopic patterns of alopecia areata: a tertiary care centre
      experience.
AB  - BACKGROUND: Dermatoscopy is a new noninvasive tool for the diagnosis of various
      skin and hair disorders. Dermatoscopy of alopecia areata (AA) shows various
      specific features, which may aid in confirming the diagnosis. AIMS: The aim of
      this study was to determine the various clinical patterns and the dermatoscopic
      features of AA. MATERIALS AND METHODS: A total of 75 patients of AA were
      evaluated with a dermatoscope (magnification *25 and *60). RESULTS: The mean age
      of onset of AA was 23.58 years. Males were more commonly affected. Scalp was most
      commonly involved. Patchy alopecia was the most common pattern observed. 10
      patients showed concomitant nail changes. The dermatoscopic features included
      yellow dots (YDs) in 43 (57.33%) patients, black dots (BDs) in 63 (84%) cases,
      broken hairs (BHs) in 28 (37.33%) cases, short vellus hair (SVH) in 51 (68%)
      patients and tapering hair (TH) in 14 (18.67%) cases. CONCLUSION: The most common
      dermatoscopic finding observed was BDs, followed by SVHs, YDs, BH and TH.

PMID- 24574692
TI  - Effects of hard water on hair.
AB  - BACKGROUND: Hardness of water is determined by the amount of salts (calcium
      carbonate [CaCO3] and magnesium sulphate [MgSO4]) present in water. The hardness
      of the water used for washing hair may cause fragility of hair. OBJECTIVE: The
      objective of the following study is to compare the tensile strength and
      elasticity of hair treated in hard water and hair treated in distilled water.
      MATERIALS AND METHODS: 10-15 strands of hair of length 15-20 cm, lost during
      combing were obtained from 15 volunteers. Each sample was cut in the middle to
      obtain 2 sets of hair per volunteer. One set of 15 samples was immersed in hard
      water and the other set in distilled water for 10 min on alternate days.
      Procedure was repeated for 30 days. The tensile strength and elasticity of the
      hair treated in hard water and distilled water was determined using INSTRON
      universal strength tester. RESULTS: The CaCO3 and MgSO4 content of hard water and
      distilled water were determined as 212.5 ppm of CaCO3 and 10 ppm of CaCO3
      respectively. The tensile strength and elasticity in each sample was determined
      and the mean values were compared using t-test. The mean (SD) of tensile strength
      of hair treated in hard water was 105.28 (27.59) and in distilled water was
      103.66 (20.92). No statistical significance was observed in the tensile strength,
      t = 0.181, P = 0.858. The mean (SD) of elasticity of hair treated in hard water
      was 37.06 (2.24) and in distilled water was 36.84 (4.8). No statistical
      significance was observed in the elasticity, t = 0.161, P = 0.874. CONCLUSION:
      The hardness of water does not interfere with the tensile strength and elasticity
      of hair.

PMID- 24574693
TI  - Trends in use of hair dye: a cross-sectional study.
AB  - OBJECTIVE: The objective of the following study was to assess the knowledge,
      practice, perception and adverse reactions among hair dye users. SETTINGS AND
      DESIGN: A cross-sectional study was conducted on patients, their attenders and
      staff of SDUMC. MATERIALS AND METHODS: A questionnaire (28) pertaining to use of
      hair dyes and reactions to them was administered randomly. STATISTICAL ANALYSIS:
      The demographic data are expressed as mean +/- standard deviation, quantitative
      data expressed as percentages. RESULTS: A total of 263 volunteers responded of
      which 52.5% and 47.5% were females and males respectively with mean age of 32.40
      +/- 6.01 years. The participants started using hair dye at an age of 27 (+/-3.63)
      years. Synthetic dyes were used by 91%. Frequency of use in a year was 2-5 times
      in 51%. Instruction of the package insert was followed by 63.5%. Skin test was
      never performed in 34% prior to their use. Nearly 96% expressed hair dyeing was
      unsafe during pregnancy, lactation and in children. Adverse reactions were
      reported by 42%, with headache (63%) and itching (38%) being the most common.
      CONCLUSION: Hair dyeing was started at very early age. Majority used semi
      permanent dyes even though they perceived natural dyes were safe. They continued
      dyeing despite adverse reactions, which indicates cosmetic importance.

PMID- 24574694
TI  - Mascara induced milphosis, an etiological evaluation.
AB  - CONTEXT: Eyelashes play an important role in one's personality and builds
      confidence. Now-a- days, mascaras are used very commonly as an eye cosmetic.
      Mascara induced loss of eyelashes has been evaluated in this study. AIM: The aim
      of this study is to determine the effect of mascara on eyelashes and to find an
      association between the usage of mascara and fall of eyelashes. SETTINGS AND
      DESIGN: Cross-sectional questionnaire based study done on medical students.
      SUBJECTS AND METHODS: Medical students were interviewed with a semi-structured
      questionnaire on mascara usage. STATISTICAL ANALYSIS: MedCalc 9.3.6.0 version.
      RESULTS: A total of 128 medical students who used mascara were included in this
      study. Mean (standard deviation) age of the students was 23.7 +/- 2.0 years.
      Nearly 31% of the subjects faced the eye problems. Eyelash fall was observed in
      19%. Higher mean years of use of mascara (5.17 +/- 3.8 vs. 3.19 +/- 2.6, P =
      0.027, t-test) influenced the fall of eyelashes in the subjects. Itching of the
      eye prior to fall of eyelashes was observed in all subjects (P = 0.0002, Fisher
      exact test). A higher percentage of eyelash falls was observed in subjects who
      used water for removal of waterproof mascara (27%). CONCLUSION: There is a
      significant positive association between long-term use of eye cosmetics like
      mascara and fall of eyelashes. Furthermore, use of water for removal of
      waterproof mascara was associated with a higher incidence of eyelash fall.

PMID- 24574695
TI  - Hair as biomarker of fluoride exposure in a fluoride endemic area and a low
      fluoridated area.
AB  - AIM: The aim of the present study was to determine whether hair could be used as
      biomarker of fluoride exposure. MATERIALS AND METHODS: The study was carried out
      on 30 people living in an endemically fluoridated area and a low fluoridated
      area. Samples of hair from the occipital were taken and subjected to fluoride
      analysis by a fluoride ion electrode. RESULTS: Lower fluoride levels in water
      supplies correlated with lower levels of fluoride in hair and more over higher
      fluoride levels in water correlated with higher levels of fluoride in hair. A
      direct relationship was evident between fluoride levels in water supplies and
      concentration of fluoride in hair (P < 0.01). CONCLUSIONS: The results of the
      present study indicate hair can be used as an indicator of fluoride exposure.

PMID- 24574696
TI  - Perifollicular erythema as a trichoscopy sign of progression in frontal fibrosing
      alopecia.
AB  - INTRODUCTION: Frontal fibrosing alopecia (FFA) in an entity characterized by the
      recession of the frontotemporal hairline (FTHL) with alopecic scarring change. In
      recent years there are numerous articles discussing the usefulness of dermoscopy
      for the clinical diagnosis of different types of scarring alopecia. MATERIALS AND
      METHODS: We value 79 patients diagnosed with FFA, evaluating some trichoscopical
      findings described as typical for FFA: Absence of follicular opening, follicular
      hyperkeratosis, follicular plugs and erythema. RESULTS: In a population of 79
      women, 100% showed no follicular opening, 72.1% follicular hyperkeratosis, 66.3%
      perifollicular erythema and 44.8% follicular plugs. Thus, 100% of patients had at
      least one of the dermoscopic elements described as suggestive of FFA, 53% two of
      them, 45% three and 27%, all those elements. Perifollicular erythema was present
      in 95% of cases in which the disease was active. CONCLUSIONS: We consider that
      the presence of perifollicular erythema will be a direct marker of FFA activity.

PMID- 24574697
TI  - Double eye brow: a rare case report.
AB  - Eye brows are essential for esthetic and functional purposes. Various kinds of
      eye brows are found in human species. Protective function is one of the important
      functions of eye brows. Double eye brow is a very rare condition found in human.
      This case report describes one of the rare cases of double eye brow. 

PMID- 24574698
TI  - Pemphigus vulgaris with loss of hair on the scalp.
AB  - Pemphigus vulgaris is an autoimmune disease, which leads to flaccid bullae and
      erosions. Although the scalp is commonly involved, hair loss is rarely seen. We
      herein report a case of 32-year-old female patient with a 2-year history of
      pemphigus vulgaris, involving the skin and mucosa. Although clinical improvement
      was achieved with oral corticosteroids and mycophenolate mofetil, the patient
      developed tender plaques on her scalp, accompanied by hair loss. Histopathology
      and direct immunofluorescence were consistent with pemphigus vulgaris. Skin swab
      cultured Staphylococcus aureus. Treatment with oral and topical corticosteroids
      combined with mycophenolate mofetil resulted in clinical remission, with regrowth
      of scalp hair. Alopecia is an unusual clinical manifestation of pemphigus
      vulgaris. Our case supports the hypothesis that hair loss is induced by antibody
      mediated outer root sheath keratinocyte acantholysis, in combination with skin
      infection, that together lead to the observed hair loss. 

PMID- 24574699
TI  - Novel Frameshift Mutation in TRPS1 in a Ukrainian Patient with
      Trichorhinophalangeal Syndrome Type I.
AB  - Trichorhinophalangeal syndrome (TRPS) type I is a rare autosomal dominant
      disorder, caused by mutations in the TRPS1 gene. It is characterized by slowly
      growing hair, craniofacial manifestations and orthopedic abnormalities. We
      present a 17-year-old female of Ukrainian origin who presented to the hair clinic
      with the complaint of hair loss. Further examination revealed the presence of
      craniofacial features characteristic for TRPS type I. Sequence analysis of the
      TRPS1 gene revealed a novel c. 2396_2397 insG frameshift mutation in exon 5,
      leading to a premature stop at codon 800. This case underlines the importance of
      the hair phenotype to the diagnosis of this syndrome and emphasizes the fact that
      when encountered with a severe alopecia in young age, the possibility of a
      congenital hair disease should always be borne in mind. 

PMID- 24574700
TI  - Pink nodule with a peculiar pattern on trichoscopy.

PMID- 24574702
TI  - Alopecia universalis in polyglandular autoimmune syndrome type I.

PMID- 24574701
TI  - Solitary calcified trichilemmal cyst on forearm.

PMID- 24574703
TI  - Prevalence of Eyelash Demodex among Human Immunodeficiency Virus Infected
      Patients at Different CD4+ Count Status.

PMID- 24574704
TI  - Epigenetics in hepatocellular carcinoma: an update and future therapy
      perspectives.
AB  - Hepatocellular carcinoma (HCC), the predominant form of adult liver malignancies,
      is a global health concern. Its dismal prognosis has prompted recent significant
      advances in the understanding of its etiology and pathogenesis. The deregulation
      of epigenetic mechanisms, which maintain heritable gene expression changes and
      chromatin organization, is implicated in the development of multiple cancers,
      including HCC. This review summarizes the current knowledge of epigenetic
      mechanisms in the pathogenesis of HCC, with an emphasis on HCC mediated by
      chronic hepatitis B virus infection. This review also discusses the encouraging
      outcomes and lessons learnt from epigenetic therapies for hematological and other
      solid cancers, and highlights the future potential of similar therapies in the
      treatment of HCC. 

PMID- 24574706
TI  - Diagnostic utility of faecal biomarkers in patients with irritable bowel
      syndrome.
AB  - Irritable bowel syndrome (IBS) is a common functional gastrointestinal (GI)
      disorder characterized by unspecific symptoms. In clinical practice it is crucial
      to distinguish between non-inflammatory functional problems and inflammatory,
      malignant or infectious diseases of the GI tract. Differentiation between these
      involves the use of clinical, radiological, endoscopic, histological and
      serological techniques, which are invasive, expensive, time-consuming and/or
      hindered by inaccuracies arising from subjective components. A range of faecal
      markers now appears to have the potential to greatly assist in the
      differentiation of inflammatory bowel disease (IBD) and IBS. Faecal markers of
      neutrophil influx into the mucosa are reliable indicators of intestinal
      inflammation and their role has been mainly studied in discriminating IBD from
      non-IBD conditions (including IBS) rather than organic from non-organic diseases.
      Phagocyte-specific proteins of the S100 family (S100A12, calprotectin) are
      amongst the most promising faecal biomarkers of inflammation. Faecal leukocyte
      degranulation markers (lactoferrin, polymorphonuclear elastase and
      myeloperoxidase) have also been suggested as diagnostic tools for the
      differentiation of IBD and IBS. More recently, additional proteins, including
      granins, defensins and matrix-metalloproteases, have been discussed as
      differential diagnostic markers in IBD and IBS. In this review, some of the most
      promising faecal markers, which have the potential to differentiate IBD and IBS
      and to advance diagnostic practices, will be discussed. 

PMID- 24574705
TI  - Complementary and alternative medicines in irritable bowel syndrome: an
      integrative view.
AB  - Irritable bowel syndrome (IBS) is a common gastrointestinal disorder with a high
      incidence in the general population. The diagnosis of IBS is mainly based on
      exclusion of other intestinal conditions through the absence of inflammatory
      markers and specific antigens. The current pharmacological treatment approaches
      available focus on reducing symptom severity while often limiting quality of life
      because of significant side effects. This has led to an effectiveness gap for IBS
      patients that seek further relief to increase their quality of life.
      Complementary and alternative medicines (CAM) have been associated with a higher
      degree of symptom management and quality of life in IBS patients. Over the past
      decade, a number of important clinical trials have shown that specific herbal
      therapies (peppermint oil and Iberogast((r))), hypnotherapy, cognitive behavior
      therapy, acupuncture, and yoga present with improved treatment outcomes in IBS
      patients. We propose an integrative approach to treating the diverse symptoms of
      IBS by combining the benefits of and need for pharmacotherapy with known CAM
      therapies to provide IBS patients with the best treatment outcome achievable.
      Initial steps in this direction are already being considered with an increasing
      number of practitioners recommending CAM therapies to their patients if
      pharmacotherapy alone does not alleviate symptoms sufficiently.

PMID- 24574707
TI  - Molecular basis of the irritable bowel syndrome.
AB  - Irritable bowel syndrome (IBS) is a functional disorder characterized by
      abdominal pain, discomfort and bloating. The pathophysiology of IBS is poorly
      understood, but the presence of psychosocial basis is now known. There is an
      increasing number of publications supporting the role of genetics in IBS. Most of
      the variations are found in genes associated with the brain-gut axis, revealing
      the strong correlation of brain-gut axis and IBS. miRNAs, which play critical
      roles in physiological processes, are not well studied in IBS. However, so far
      there is found an involvement of alterations in miRNA expression or sequence, in
      IBS symptoms. IBS phenotype is affected by epigenetic alteration and environment.
      Changes in DNA and histone methylation are observed in patients who suffered
      childhood trauma or abuse, resulting in altered gene expression, such as the
      glucocorticoid receptor gene. Finally, diet is another factor associated with
      IBS, which may contribute to symptom onset. Certain foods may affect on bacterial
      metabolism and epigenetic modifications, predisposing to IBS. 

PMID- 24574709
TI  - Then and now: the progress in hepatitis B treatment over the past 20 years.
AB  - The ultimate goals of treating chronic hepatitis B (CHB) is prevention of
      hepatocellular carcinoma (HCC) and hepatic decompensation. Since the advent of
      effective antiviral drugs that appeared during the past two decades, considerable
      advances have been made not only in controlling hepatitis B virus (HBV)
      infection, but also in preventing and reducing the incidence of liver cirrhosis
      and HCC. Furthermore, several recent studies have suggested the possibility of
      reducing the incidence of recurrent or new HCC in patients even after they have
      developed HCC. Currently, six medications are available for HBV treatment
      including, interferon and five nucleoside/nucleotide analogues. In this review,
      we will examine the antiviral drugs and the progresses that have been made with
      antiviral treatments in the field of CHB. 

PMID- 24574710
TI  - Outcomes and management of viral hepatitis and human immunodeficiency virus co
      infection in liver transplantation.
AB  - Liver transplantation for human immunodeficiency virus (HIV) positive patients
      with viral hepatitis co-infection is increasingly offered in many North American
      and European liver transplant centers. Prior studies have demonstrated acceptable
      post-transplant outcomes and no increased risk of HIV complications in patients
      co-infected with hepatitis B virus (HBV). However, liver transplantation in HIV
      positive patients with hepatitis C virus (HCV) has poorer outcomes overall,
      requiring careful selection of candidates. This review aims to summarize the
      published literature on outcomes after transplant in HIV patients with HBV or HCV
      related end-stage liver disease and recommendations for management. In particular
      the pre-transplant factors impacting outcomes in HCV/HIV co-infected candidates
      and importance of multidisciplinary management will be discussed. 

PMID- 24574711
TI  - Core promoter: a critical region where the hepatitis B virus makes decisions.
AB  - The core promoter (CP) of the viral genome plays an important role for hepatitis
      B virus (HBV) replication as it directs initiation of transcription for the
      synthesis of both the precore and pregenomic (pg) RNAs. The CP consists of the
      upper regulatory region and the basal core promoter (BCP). The CP overlaps with
      the 3'-end of the X open reading frames and the 5'-end of the precore region, and
      contains cis-acting elements that can independently direct transcription of the
      precore mRNA and pgRNA. Its transcription regulation is under strict control of
      viral and cellular factors. Even though this regulatory region exhibits high
      sequence conservation, when variations appear, they may contribute to the
      persistence of HBV within the host, leading to chronic infection and cirrhosis,
      and eventually, hepatocellular carcinoma. Among CP sequence variations, those
      occurring at BCP may dysregulate viral gene expression with emphasis in the
      hepatitis B e antigen, and contribute to disease progression. In this review
      these molecular aspects and pathologic topics of core promoter are deeply
      evaluated.

PMID- 24574712
TI  - Is hepatitis B-virucidal validation of biocides possible with the use of
      surrogates?
AB  - The hepatitis B virus (HBV) is considered to be a major public health problem
      worldwide, and a significant number of reports on nosocomial outbreaks of HBV
      infections have been reported. Prevention of indirect HBV transmission by
      contaminated objects is only possible through the use of infection-control
      principles, including the use of chemical biocides, which are proven to render
      the virus non-infectious. The virucidal activity of biocides against HBV cannot
      be predicted; therefore, validation of the virucidal action of disinfectants
      against HBV is essential. However, feasible HBV infectivity assays have not yet
      been established. Thus, surrogate models have been proposed for testing the
      efficacy of biocides against HBV. Most of these assays do not correlate with HBV
      infectivity. Currently, the most promising and feasible assay is the use of the
      taxonomically related duck hepatitis B virus (DHBV), which belongs to the same
      Hepadnaviridae virus family. This paper reviews the application of DHBV, which
      can be propagated in vitro in primary duck embryonic hepatocytes, for the testing
      of biocides and describes why this model can be used as reliable method to
      evaluate disinfectants for efficacy against HBV. The susceptibility levels of
      important biocides, which are often used as ingredients for commercially
      available disinfectants, are also described. 

PMID- 24574714
TI  - Hepatitis B virus mutations related to liver disease progression of Korean
      patients.
AB  - Hepatitis B virus (HBV) infection is a global health problem and more than 350
      million people worldwide are chronic carriers of the virus. Despite the recent
      dramatic decline in HBV chronic patients through successful programs of hepatitis
      B surface antigen vaccination, South Korea is still recognized as an endemic area
      of HBV infection. HBV infections in South Korea exhibit several distinct features
      in epidemiologic and clinical aspects. In this review paper, we summarize the
      distinct HBV mutation patterns related to clinical severity and the molecular
      epidemiologic traits in Korean chronic patients based on previous reports.
      Generally, several lines of evidence, including our previous results, have led to
      the conclusion that a combination of the exclusive predominance of genotype C2,
      which is prone to mutations, the high prevalence of basal core promoter double
      mutations, and the presence of distinct immune responses against HBV proteins in
      the Korean population may generate the distinct HBV variants rarely or not
      encountered in other areas, which results in distinct clinical manifestations in
      Korean chronic patients. This may provide a novel insight into the relationships
      between clinical severity, HBV genotype distribution, and HBV naturally occurring
      variants. 

PMID- 24574708
TI  - Is irritable bowel syndrome an organic disorder?
AB  - Irritable bowel syndrome (IBS) is a common gastrointestinal disorder that is
      generally considered to be functional because there appears to be no associated
      anatomical defect. Stress and psychological factors are thought to play an
      important role in IBS. The gut neuroendocrine system (NES), which regulates all
      functions of the gastrointestinal tract, consists of endocrine cells that are
      scattered among the epithelial cells of the mucosa, and the enteric nervous
      system. Although it is capable of operating independently from the central
      nervous system (CNS), the gut NES is connected to and modulated by the CNS. This
      review presents evidence for the presence of an anatomical defect in IBS
      patients, namely in the gastrointestinal endocrine cells. These cells have
      specialized microvilli that project into the lumen and function as sensors for
      the luminal content and respond to luminal stimuli by releasing hormones into the
      lamina propria, which starts a chain reaction that progresses throughout the
      entire NES. The changes in the gastrointestinal endocrine cells observed in IBS
      patients are highly consistent with the other abnormalities reported in IBS
      patients, such as visceral hypersensitivity, dysmotility, and abnormal secretion.

PMID- 24574715
TI  - Evolution of hepatitis B management in kidney transplantation.
AB  - Chronic hepatitis B virus (HBV) infection adversely influences the clinical
      outcomes of renal transplant recipients owing to increased hepatic complications.
      Management of HBV infection in kidney transplant recipients presents a challenge
      to clinicians, especially in endemic regions. Interferon precipitates renal
      allograft dysfunction. Treatment with lamivudine, the first oral nucleoside
      analogue available, resulted in effective viral suppression, reduced liver
      related complications, and improved patient survival so that medium-term data
      showed comparable patient survival rates between hepatitis B surface antigen
      positive and HBsAg-negative kidney transplant recipients in the era of effective
      antiviral therapies. Entecavir has replaced lamivudine as first-line therapy for
      treatment-naive subjects in view of the propensity for drug resistance with the
      latter. Management of HBV infection in kidney transplant patients needs to take
      into consideration the nephrotoxicity of nucleoside/tide analogues such as
      adefovir and tenofovir. Prevention of HBV-related complications in kidney
      transplant recipients starts much earlier prior to transplantation, with
      vaccination of patients with chronic kidney disease and donor-recipient matching
      with regard to HBV status. In addition to anti-viral treatment, patients with
      chronic HBV infection must have regular surveillance for liver cancer and
      assessment for the development of cirrhosis.

PMID- 24574713
TI  - Non-invasive diagnosis of hepatitis B virus-related cirrhosis.
AB  - Chronic hepatitis B (CHB) infection is a major public health problem associated
      with significant morbidity and mortality worldwide. Twenty-three percent of
      patients with CHB progress naturally to liver cirrhosis, which was earlier
      thought to be irreversible. However, it is now known that cirrhosis can in fact
      be reversed by treatment with oral anti-nucleotide drugs. Thus, early and
      accurate diagnosis of cirrhosis is important to allow an appropriate treatment
      strategy to be chosen and to predict the prognosis of patients with CHB. Liver
      biopsy is the reference standard for assessment of liver fibrosis. However, the
      method is invasive, and is associated with pain and complications that can be
      fatal. In addition, intra- and inter-observer variability compromises the
      accuracy of liver biopsy data. Only small tissue samples are obtained and
      fibrosis is heterogeneous in such samples. This confounds the two types of
      observer variability mentioned above. Such limitations have encouraged
      development of non-invasive methods for assessment of fibrosis. These include
      measurements of serum biomarkers of fibrosis; and assessment of liver stiffness
      via transient elastography, acoustic radiation force impulse imaging, real-time
      elastography, or magnetic resonance elastography. Although significant advances
      have been made, most work to date has addressed the diagnostic utility of these
      techniques in the context of cirrhosis caused by chronic hepatitis C infection.
      In the present review, we examine the advantages afforded by use of non-invasive
      methods to diagnose cirrhosis in patients with CHB infections and the utility of
      such methods in clinical practice. 

PMID- 24574716
TI  - Limitations of liver biopsy and non-invasive diagnostic tests for the diagnosis
      of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis.
AB  - It is estimated that 30% of the adult population in Japan is affected by
      nonalcoholic fatty liver disease (NAFLD). Fatty changes of the liver are
      generally diagnosed using imaging methods such as abdominal ultrasonography (US)
      and computed tomography (CT), but the sensitivity of these imaging techniques is
      low in cases of mild steatosis. Alanine aminotransferase levels may be normal in
      some of these patients, warranting the necessity to establish a set of parameters
      useful for detecting NAFLD, and the more severe form of the disease, nonalcoholic
      steatohepatitis (NASH). Although liver biopsy is currently the gold standard for
      diagnosing progressive NASH, it has many drawbacks, such as sampling error, cost,
      and risk of complications. Furthermore, it is not realistic to perform liver
      biopsies on all NAFLD patients. Diagnosis of NASH using various biomarkers,
      scoring systems and imaging methods, such as elastography, has recently been
      attempted. The NAFIC score, calculated from the levels of ferritin, fasting
      insulin, and type IV collagen 7S, is useful for the diagnosis of NASH, while the
      NAFLD fibrosis score and the FIB-4 index are useful for excluding NASH in cases
      of advanced fibrosis. This article reviews the limitations and merits of liver
      biopsy and noninvasive diagnostic tests in the diagnosis of NAFLD/NASH.

PMID- 24574717
TI  - Molecular targeting agents associated with transarterial chemoembolization or
      radiofrequency ablation in hepatocarcinoma treatment.
AB  - Hepatocellular carcinoma (HCC) is the fifth most common cause of cancer in the
      world. According to Barcelona Clinic Liver Cancer modified criteria, patients
      with early stage disease are candidate to radiofrequency ablation (RFA), while
      patients with intermediate stage HCC are usually treated by transarterial
      chemoembolization (TACE). TACE and RFA induce a transient devascularisation
      effect followed by strong neo-angiogenic stimulus. In fact, after these
      procedures, it has been demonstrated an up-regulation of pro-angiogenic and
      growth factors such as vascular endothelial growth factor-A, which might
      contribute to accelerated progression in patients with incomplete response.
      Several studies have demonstrated that MAP-kinase and AKT pathways, in addition
      to neo-angiogenesis, have an important role in the development of HCC. In
      advanced HCC, anti-angiogenic therapy and tyrosine kinases inhibitors showed
      potential clinical benefit. Actually, a number of clinical studies are ongoing
      testing these agents in combination with TACE or RFA. In this paper, we have
      reviewed the most recent preclinical and clinical results of such trials.

PMID- 24574718
TI  - Deletion of Gpr128 results in weight loss and increased intestinal contraction
      frequency.
AB  - AIM: To generate a Gpr128 gene knockout mouse model and to investigate its
      phenotypes and the biological function of the Gpr128 gene. METHODS: Bacterial
      artificial chromosome-retrieval methods were used for constructing the targeting
      vector. Using homologous recombination and microinjection technology, a Gpr128
      knockout mouse model on a mixed 129/BL6 background was generated. The mice were
      genotyped by polymerase chain reaction (PCR) analysis of tail DNA and fed a
      standard laboratory chow diet. Animals of both sexes were used, and the
      phenotypes were assessed by histological, biochemical, molecular and
      physiological analyses. Semi-quantitative reverse transcription-PCR and Northern
      blotting were used to determine the tissue distribution of Gpr128 mRNA. Beginning
      at the age of 4 wk, body weights were recorded every 4 wk. Food, feces, blood and
      organ samples were collected to analyze food consumption, fecal quantity, organ
      weight and constituents of the blood and plasma. A Trendelenburg preparation was
      utilized to examine intestinal motility in wild-type (WT) and Gpr128(-/-) mice at
      the age of 8 and 32 wk. RESULTS: Gpr128 mRNA was highly and exclusively detected
      in the intestinal tissues. Targeted deletion of Gpr128 in adult mice resulted in
      reduced body weight gain, and mutant mice exhibited an increased frequency of
      peristaltic contraction and slow wave potential of the small intestine. The
      Gpr128(+/+) mice gained more weight on average than the Gpr128(-/-) mice since 24
      wk, being 30.81 +/- 2.84 g and 25.74 +/- 4.50 g, respectively (n = 10, P < 0.01).
      The frequency of small intestinal peristaltic contraction was increased in
      Gpr128(-/-) mice. At the age of 8 wk, the frequency of peristalsis with an
      intraluminal pressure of 3 cmH2O was 6.6 +/- 2.3 peristalsis/15 min in Gpr128(-/
      ) intestine (n = 5) vs 2.6 +/- 1.7 peristalsis/15 min in WT intestine (n = 5, P <
      0.05). At the age of 32 wk, the frequency of peristaltic contraction with an
      intraluminal pressure of 2 and 3 cmH2O was 4.6 +/- 2.3 and 3.1 +/- 0.8
      peristalsis/15 min in WT mice (n = 8), whereas in Gpr128(-/-) mice (n = 8) the
      frequency of contraction was 8.3 +/- 3.0 and 7.4 +/- 3.1 peristalsis/15 min,
      respectively (2 cmH2O: P < 0.05 vs WT; 3 cmH2O: P < 0.01 vs WT). The frequency of
      slow wave potential in Gpr128(-/-) intestine (35.8 +/- 4.3, 36.4 +/- 4.2 and 37.1
      +/- 4.8/min with an intraluminal pressure of 1, 2 and 3 cmH2O, n = 8) was also
      higher than in WT intestine (30.6 +/- 4.2, 31.4 +/- 3.9 and 31.9 +/- 4.5/min, n =
      8, P < 0.05). CONCLUSION: We have generated a mouse model with a targeted
      deletion of Gpr128 and found reduced body weight and increased intestinal
      contraction frequency in this animal model.

PMID- 24574719
TI  - Long-term follow-up of ulcerative colitis patients treated on the basis of their
      cytomegalovirus antigen status.
AB  - AIM: To clarify the impact of cytomegalovirus (CMV) activation and antiviral
      therapy based on CMV antigen status on the long-term clinical course of
      ulcerative colitis (UC) patients. METHODS: UC patients with flare-up were divided
      into CMV-positive and -negative groups according to the CMV antigenemia assay.
      The main treatment strategy provided for the patients in the CMV-positive group
      comprised a dose reduction of corticosteroids and administration of ganciclovir.
      RESULTS: The median number of days to initial remission was significantly greater
      for the patients in the CMV-positive group (21 d vs 16 d, P = 0.009). However,
      the relapse rate after remission and colectomy rate during more than 30 mo of
      observation did not differ between the two groups. Multivariate analysis revealed
      that administration of ganciclovir was the only independent factor for avoiding
      colectomy in patients of the CMV-positive group. CONCLUSION: CMV antigen status
      did not significantly affect the long-term prognosis in UC patients under
      treatment with appropriate antiviral therapy.

PMID- 24574720
TI  - Effectiveness of contrast-enhanced harmonic endoscopic ultrasound for the
      evaluation of solid pancreatic masses.
AB  - AIM: To evaluate the usefulness of contrast-enhanced harmonic endoscopic
      ultrasound (CH-EUS) in differentiating between pancreatic adenocarcinomas and
      other pancreatic disease. METHODS: This retrospective cohort study evaluated 90
      patients who were seen between November 2010 and May 2013. All these patients had
      solid pancreatic masses that had a hypoechoic appearance on EUS. All patients
      underwent CH-EUS to evaluate this diagnostic method's usefulness. The mass
      lesions observed on CH-EUS were classified into three categories based on their
      echo intensity: hypoenhanced, isoenhanced, and hyperenhanced lesions. We adjusted
      the sensitivity and the specificity of each category for detecting malignancies.
      We also estimated the accuracy of CH-EUS by comparing it to a pathological
      diagnosis. RESULTS: Of the 90 patients, 62 had a pancreatic adenocarcinoma. Fifty
      seven out of 62 pancreatic adenocarcinomas showed a hypoenhanced pattern on CH
      EUS. The sensitivity was 92%, the specificity 68% and the accuracy approximately
      82%. The area under the curve of the receiver operating characteristic analysis
      for CH-EUS was 0.799. There is a significant association between the hypoenhanced
      pattern on CH-EUS and pancreatic duct adenocarcinoma (chi(2) = 35.264, P <
      0.001). In pathological examinations, the number of specimens for EUS-fine needle
      aspiration (EUS-FNA) was considered insufficient for diagnosis in three patients,
      and in two patients, the results were reported to be negative for malignancy.
      Pancreatic masses in all five patients revealed a hypoenhanced pattern with CH
      EUS. Three patients were diagnosed with pancreatic adenocarcinoma based on the
      pathology results of a biopsy, and the remaining two patients were clinically
      diagnosed with malignancy. CONCLUSION: CH-EUS is useful for distinguishing
      between pancreatic adenocarcinoma and other pancreatic disease. When a pancreatic
      mass shows a hypoenhanced pattern on CH-EUS but involves either insufficient
      samples or negative results with EUS-FNA, clinicians might consider performing
      another pathologic diagnosis on the basis of an EUS-FNA sample or a biopsy.

PMID- 24574721
TI  - Comparative analysis of radiofrequency ablation and resection for resectable
      colorectal liver metastases.
AB  - AIM: To evaluate the therapeutic efficacy of radiofrequency ablation (RFA) for
      resectable colorectal liver metastases (CRLM) compared with that of resection.
      METHODS: Between June 2004 and June 2009, we retrospectively analyzed 29 patients
      with resectable CRLMs; 17 patients underwent RFA, and 12 underwent hepatic
      resection. All of the patients were informed about the treatment modalities and
      were allowed to choose either of them. RFA including an intraoperative approach
      was performed by a radiologist; otherwise, hepatic resection was performed by a
      surgeon. Comparative analysis of the two groups was performed, including
      comparisons of gender, age, and clinical outcomes, such as primary tumor stage
      and survival rates. RESULTS: The mean tumor size was significantly larger in the
      resection group (3.59 cm vs 2.02 cm, P < 0.01), and the 5-year overall survival
      (OS) rate for all patients was 44.7%. There was no difference in the 5-year OS
      rates between the RFA and resection groups (37.8% vs 66.7%). Univariate analysis
      indicated significantly lower 5-year OS rates for patients with a tumor size > 3
      cm. The 5-year disease-free survival (DFS) rates were 17.6% and 22.2% in the RFA
      and resection groups, respectively (P = 0.119). Univariate analysis revealed that
      in cases of male gender, age > 65 years, T stage < IV, absence of lymphatic
      metastasis, and tumor size > 3 cm, RFA resulted in significantly inferior 5-year
      DFS rates compared with surgical resection. CONCLUSION: Surgical resection
      revealed superior outcomes in the treatment of resectable CRLMs, particularly in
      cases with a hepatic tumor size > 3 cm.

PMID- 24574722
TI  - Incidence trends and predictors for cost and average lengths of stay in
      colorectal cancer surgery.
AB  - AIM: To evaluate the changing trends and outcomes of colorectal cancer (CRC)
      surgery performed at a large single institution in Taiwan. METHODS: This study
      retrospectively analyzed 778 patients who received colorectal cancer surgery at E
      Da Hospital in Taiwan from 2004 to 2009. These patients were from health
      examination, inpatient or emergency settings. The following attributes were
      analyzed in patients who had undergone CRC surgical procedures: gender, age,
      source, surgical type, tumor number, tumor size, number of lymph node metastasis,
      pathologic differentiation, chemotherapy, distant metastases, tumor site, tumor
      stage, average hospitalization cost and average lengths of stay (ALOS). The odds
      ratio and 95% confidence intervals were calculated to assess the relative rate of
      change. Regression models were employed to predict average hospitalization cost
      and ALOS. RESULTS: The study sample included 458 (58.87%) males and 320 (41.13%)
      females with a mean age of 64.53 years (standard deviation, 12.33 years; range,
      28-86 years). The principal patient source came from inpatient and emergency room
      (96.02%). The principal tumor sites were noted at the sigmoid colon (35.73%) and
      rectum (30.46%). Most patients exhibited a tumor stage of 2 (37.28%) or 3
      (34.19%). The number of new CRC surgeries performed per 100000 persons was 12.21
      in 2004 and gradually increased to 17.89 in 2009, representing a change of
      46.52%. During the same period, the average hospitalization cost and ALOS
      decreased from $5303 to $4062 and from 19.7 to 14.4 d, respectively. The
      following factors were associated with considerably decreased hospital resource
      utilization: age, source, surgical type, tumor size, tumor site, and tumor stage.
      CONCLUSION: These results can be generalized to patient populations elsewhere in
      Taiwan and to other countries with similar patient profiles.

PMID- 24574723
TI  - Hyperamylasemia is associated with increased intestinal permeability in patients
      undergoing diagnostic oral double-balloon enteroscopy.
AB  - AIM: To investigate the correlations between serum amylase levels, intestinal
      permeability (IP), and pancreatic injury and to explore the mechanisms
      responsible for hyperamylasemia in double-balloon enteroscopy (DBE). METHODS: A
      prospective study was conducted in 20 patients who underwent DBE from August 1,
      2008 to February 28, 2009. Serum amylase was examined 0, 2, 6 and 24 h post-DBE,
      C-reactive protein and lipase were examined at 24 h, and urine lactulose,
      mannitol, and trypsinogen-II (TRY-II) levels were measured at 6 h.
      Lactulose/mannitol ratio indicated IP, and TRY-II indicated pancreatic injuries.
      Procedure duration and enteroscope insertion length were recorded. RESULTS:
      Twelve patients underwent oral DBE (M:F, 5:7; mean age 50.42 +/- 11.11 years) and
      8 underwent anal DBE (M:F, 5:3; mean age 44.75 +/- 12.66 years). They all showed
      significantly increased post-DBE serum amylase. Amylase and lipase levels were
      higher in the oral DBE group (P < 0.05). Hyperamylasemia was diagnosed in 9
      (75.0%) patients undergoing oral DBE. Only patients receiving oral DBE showed
      increased post-procedure IP, which correlated with increased serum amylase (r =
      0.611, P = 0.035) and procedure duration (r = 0.668, P = 0.018). Adverse events
      included one oral case with pancreatic injury (elevated TRY-II) and two cases of
      abdominal discomfort in each group. Pancreatitis was not reported. CONCLUSION:
      Hyperamylasemia correlates with increased IP and clinically undetectable
      pancreatic injuries. DBE could cause intestinal mucosa damage, which may result
      in IP elevation and increased amylase absorption, necessitating improvements and
      standardization of DBE methods.

PMID- 24574725
TI  - Total splenic artery embolization for splenic artery aneurysms in patients with
      normal spleen.
AB  - AIM: To evaluate total embolization of the main splenic artery in patients with
      splenic artery aneurysms (SAAs) and normal spleen. METHODS: Thirty-five
      consecutive patients with SAAs were referred for treatment with coil
      embolization. Patients were classified into two groups: coil embolization of the
      main splenic artery with complete occlusion of the artery and aneurysms (group A,
      n = 16), and coil embolization of the aneurysmal sac with patency of the splenic
      artery (group B, n = 19). Data on white blood cell (WBC) and platelet counts,
      liver function, and complications were collected on days 7 and 30, and
      subsequently at a 6-mo interval postoperatively. Abdominal computed tomography
      was routinely performed to calculate the splenic volume before and 1 mo after the
      procedure, and subsequently every 6 mo during follow-up. RESULTS: Coil
      embolization of the SAAs was technically successful in all 35 patients, with no
      procedure-related complications. The post-embolization syndrome, including
      abdominal pain, fever and vomiting, occurred in six patients (37.5%) in group A
      and three patients in group B (15.8%). There were no significant differences in
      WBC and platelet counts between preoperatively and at each follow-up point after
      the procedures. There were also no significant differences in average WBC and
      platelet counts between the two groups at each follow-up point. There were
      significant differences in splenic volume in group A between preoperatively and
      at each follow-up point, and there were also significant differences in splenic
      volume between the two groups at each follow-up point. CONCLUSION: Total
      embolization of the main splenic artery was a safe and feasible procedure for
      patients with SAAs and normal spleen.

PMID- 24574724
TI  - Consecutive laparoscopic gallbladder and spleen resections in cirrhotic patients.
AB  - AIM: To evaluate the feasibility, safety, and effectiveness of consecutive
      laparoscopic cholecystectomy (LC) plus splenectomy (LS) in liver cirrhosis
      patients. METHODS: From 2003 to 2013, 17 (group 1) patients with liver cirrhosis
      complicated by hypersplenism and symptomatic gallstones were treated with
      combined LC and LS, while 58 (group 2) patients with liver cirrhosis and
      hypersplenism received LS alone. An additional 14 (group 3) patients who received
      traditional open procedures during the same period were included as controls.
      Data were retrospectively collected and reviewed in regard to demographic
      characteristics and preoperative, intraoperative and postoperative features.
      Differences between the three groups were assessed by statistical analysis.
      RESULTS: The three groups showed no significant differences in the demographic
      characteristics or preoperative status. However, the patients treated with LC and
      LS required significantly longer operative time, shorter postoperative stay as
      well as shorter time of return to the first oral intake, and suffered less
      intraoperative blood loss as well as fewer postoperative surgical infections than
      the patients treated with traditional open procedures (group 1 vs group 3, P <
      0.05 for all). The patients treated with LC and LS showed no significant
      differences in the intraoperative and postoperative variables from those treated
      with LS alone (group 1 vs group 2). All patients showed significant improvements
      in the haematological responses (preoperative period vs postoperative period, P <
      0.05 for all). None of the patients treated with LC and LS presented with any
      gallstone-associated symptoms following discharge, while the patients treated
      with the traditional open procedures expressed complaints of discomfort related
      to their surgical incisions. CONCLUSION: Consecutive LC and LS is an appropriate
      treatment option for liver cirrhosis patients with gallstones and hypersplenism,
      especially for those with Child-Pugh A and B.

PMID- 24574726
TI  - Xiangshaliujunzi Decoction for the treatment of diabetic gastroparesis: a
      systematic review.
AB  - AIM: To assess the current clinical evidence of the effectiveness of
      Xiangshaliujunzi Decoction (XSLJZD) for the treatment of diabetic gastroparesis
      (DGP). METHODS: Randomized controlled trials (RCTs) were retrieved from seven
      major electronic databases including Medline, the Cochrane Library, Embase,
      Chinese Biomedical Literature Database (CBM), Chinese National Knowledge
      Infrastructure, Chinese Scientific Journal Database (VIP), and Wanfang Databases,
      using search dates from the beginning of the databases to May 2013. No language
      limitations were applied. We included RCTs that used XSLJZD or a modified XSLJZD
      compared with a control group for the treatment of DGP. The control groups
      included conventional treatment (Western medicinal treatment), placebo, and no
      treatment (blank), but not acupuncture. The main outcome index was clinical
      effectiveness, which was based on the gastric emptying test and variations in the
      gastrointestinal (GI) symptoms between the treatment and control groups after
      intervention. Data extraction, analysis, and quality assessment were conducted
      according to the Cochrane Handbook for Systematic Review of Interventions,
      Version 5.1.0. RESULTS: Ten RCTs involving 867 patients (441 in the experimental
      groups, and 426 in the control groups) were identified, and the overall
      methodological quality was evaluated as generally low. In the treatment groups,
      all 10 trials used herbs alone as the treatment, whereas all control groups used
      prokinetic medicine. The period of intervention ranged from 2 to 8 wk. Three
      classes were used to evaluate treatment efficacy: significant effective,
      effective, and ineffective, and all trials used the clinical effective rate
      (based on the gastric emptying test and changes in GI symptoms) to evaluate
      efficacy. The data showed that the effects of XSLJZD for the treatment of DGP
      were superior to the control group (n = 867, RR =1.33, 95%CI: 1.24-1.42, Z =
      8.11, P < 0.00001). Two trials recorded adverse events, and one trial reported
      follow-up. CONCLUSION: XSLJZD could restore the gastric emptying rate and improve
      symptoms. However, the evidence remains weak due to the poor methodological
      quality of the included studies.

PMID- 24574727
TI  - Effects of pentoxifylline on nonalcoholic fatty liver disease: a meta-analysis.
AB  - AIM: To evaluate the effects of pentoxifylline therapy in patients with
      nonalcoholic fatty liver disease (NAFLD). METHODS: We searched PubMed, Medline,
      Google Scholar, Embase, Web of Science, the Cochrane Library and the Chinese
      Biomedicine Database for all relevant controlled trials of pentoxifylline in
      patients with NAFLD from 1997 to July 2013. Five studies (3 randomized, double
      blind, placebo-controlled trials and 2 prospective cohort studies with concurrent
      controls) were included in this meta-analysis. Statistical analysis was performed
      using RevMan 5.0 software. RESULTS: Five randomized trials of 147 patients with
      NAFLD/nonalcoholic steatohepatitis (NASH) were included. The results showed that
      compared to placebo, pentoxifylline therapy resulted in a significant decrease in
      body weight (P = 0.04), alanine aminotransferase (P < 0.00001), aspartate
      transaminase (P = 0.0006), glucose (P = 0.0008) and tumor necrosis factor-alpha
      (P = 0.007), but did not significantly affect body mass index (P = 0.28), total
      cholesterol (P = 0.80), triglyceride (P = 0.98), alkaline phosphatase (P = 0.29),
      gamma-glutamyl transferase (P = 0.39) and interleukin-6 (P = 0.38). With regard
      to histological changes, pentoxifylline only reduced the NAFLD activity score (P
      < 0.00001) and improved lobular inflammation (P < 0.0001). Improvements in
      steatosis grade (P = 0.11), ballooning (P = 0.10) and fibrosis (P = 0.50) were
      not obvious. CONCLUSION: Pentoxifylline therapy results in weight loss, improved
      liver function and histological changes in patients with NAFLD/NASH. Therefore,
      pentoxifylline may be a new treatment option for NAFLD.

PMID- 24574728
TI  - Fast-track program vs traditional care in surgery for gastric cancer.
AB  - AIM: To systematically review the evidence for the effectiveness of fast-track
      program vs traditional care in laparoscopic or open surgery for gastric cancer.
      METHODS: PubMed, Embase and the Cochrane library databases were electronically
      searched for published studies between January 1995 and April 2013, and only
      randomized trials were included. The references of relevant studies were manually
      searched for further studies that may have been missed. Search terms included
      "gastric cancer", "fast track" and "enhanced recovery". Five outcome variables
      were considered most suitable for analysis: postoperative hospital stay, medical
      cost, duration to first flatus, C-reactive protein (CRP) level and complications.
      Postoperative hospital stay was calculated from the date of operation to the date
      of discharge. Fixed effects model was used for meta-analysis. RESULTS: Compared
      with traditional care, fast-track program could significantly decrease the
      postoperative hospital stay [weighted mean difference (WMD) = -1.19, 95%CI: -1.79
      -0.60, P = 0.0001, fixed model], duration to first flatus (WMD = -6.82, 95%CI: 
      11.51--2.13, P = 0.004), medical costs (WMD = -2590, 95%CI: -4054--1126, P =
      0.001), and the level of CRP (WMD = -17.78, 95%CI: -32.22--3.35, P = 0.0001) in
      laparoscopic surgery for gastric cancer. In open surgery for gastric cancer, fast
      track program could also significantly decrease the postoperative hospital stay
      (WMD = -1.99, 95%CI: -2.09--1.89, P = 0.0001), duration to first flatus (WMD = 
      12.0, 95%CI: -18.89--5.11, P = 0.001), medical cost (WMD = -3674, 95%CI: -5025-
      2323, P = 0.0001), and the level of CRP (WMD = -27.34, 95%CI: -35.42--19.26, P =
      0.0001). Furthermore, fast-track program did not significantly increase the
      incidence of complication (RR = 1.39, 95%CI: 0.77-2.51, P = 0.27, for
      laparoscopic surgery; and RR = 1.52, 95%CI: 0.90-2.56, P = 0.12, for open
      surgery). CONCLUSION: Our overall results suggested that compared with
      traditional care, fast-track program could result in shorter postoperative
      hospital stay, less medical costs, and lower level of CRP, with no more
      complications occurring in both laparoscopic and open surgery for gastric cancer.

PMID- 24574729
TI  - Chemotherapy for patients with gastric cancer after complete resection: a network
      meta-analysis.
AB  - AIM: To conduct a network meta-analysis to evaluate the effectiveness of
      different chemotherapy regimens for patients with gastric cancer. METHODS: PubMed
      (1966-2011.12), the Cochrane Library (2011 Issue 2) and EMBASE (1974-2011.12)
      were searched with the terms "gastric cancer" and "chemotherapy", as well as the
      medical subject headings. References from relevant articles and conferences were
      also included. Patients who had previous gastric surgery, radiation before or
      after surgery or chemotherapy before surgery were excluded. In this study, only
      randomized controlled trials (RCTs) were considered, and the end-point was the
      overall mortality. Direct comparisons were performed using traditional meta
      analysis whereas indirect comparisons were performed using network meta-analysis.
      RESULTS: In total, 31 RCTs with 7120 patients were included. Five chemotherapy
      regimens, fluorouracil (FU) + BCNU, FU + methyl-CCNU (mCCNU), FU + cisplatin, FU
      + anthracyclines and FU + mitomycin c (MMC) + cytarabine (Ara-c), were found to
      be less beneficial in terms of overall mortality. In contrast, four chemotherapy
      regimens were effective for the patients after surgery, including FU + MMC +
      adriamycin (FMA), FU + MMC (FM), Tegafur and MMC, There was no significant
      difference in terms of overall mortality among these regimens. The evidence for
      the FM regimen and MMC regimen was poor. Additionally, the FMA regimen, which
      includes a variety of chemotherapy drugs and causes many side effects, was not
      better than the Tegafur regimen. CONCLUSION: Although the four chemotherapy
      regimens were effective in patients with gastric cancer after surgery and the
      overall mortality revealed no significant difference among them in the network
      meta-analysis, thorough analysis of the results recommends Tegafur as the first
      line adjuvant chemotherapy regimen for patients after complete resection.

PMID- 24574730
TI  - An extremely rare case of pancreatic metastasis of esophageal squamous cell
      carcinoma.
AB  - We report a rare case of a 68-year-old male with metachronous pancreatic
      metastasis that was resected 2 years after salvage esophagectomy for local
      recurrence of esophageal squamous cell carcinoma (ESCC). Two years and 8 mo ago,
      he had undergone definitive chemoradiotherapy for the lower thoracic ESCC and
      achieved a complete response. Chemoradiotherapy used the protocol of the Japan
      Clinical Oncology Group trial 9906. Approximately 8 mo later, he developed a
      local recurrence of the ESCC and underwent thoracoscopic salvage esophagectomy
      followed by reconstruction with a conduit colon graft via a subcutaneous route.
      Recently, a tumor of the pancreatic body was found on routine follow-up computed
      tomography (CT). The tumor diameter was 15 mm on CT, and the maximum standardized
      uptake value of the lesion was 5.49 at 18F-2-fluoro-2-deoxy-D-glucose positron
      emission tomography, strongly suggesting pancreatic cancer. In addition, all
      tumor markers were within the reference intervals. Therefore, distal
      pancreatectomy was performed with the resultant histological diagnosis being
      confirmed as pancreatic metastasis of the ESCC. He was treated with adjuvant
      chemotherapy, and there has been no evidence of recurrence 9 mo after the
      surgery. Resection of pancreatic metastasis offers a good prognosis and should be
      considered for solitary ESCC metastasis. 

PMID- 24574731
TI  - Intestinal anisakiasis treated successfully with conservative therapy: importance
      of clinical diagnosis.
AB  - Intestinal anisakiasis is not only a rare parasitic disease, but is also
      difficult to diagnose. The symptoms are not specific and are often very severe
      and abrupt, and the findings of clinical imaging are very remarkable. Therefore,
      intestinal anisakiasis is often misdiagnosed as acute abdomen or intestinal
      obstruction and is treated surgically. However, if intestinal anisakiasis could
      be diagnosed correctly, it is well treated conservatively. We experienced three
      cases of intestinal anisakiasis, which were diagnosed correctly and treated
      successfully with conservative therapy. A correct clinical history and imaging
      interpretation helped us diagnose intestinal anisakiasis correctly and thus treat
      the patients successfully with conservative therapy. 

PMID- 24574733
TI  - ERCP for patients who have undergone Billroth II gastroenterostomy and Braun
      anastomosis.
AB  - Endoscopic retrograde cholangiopancreatography (ERCP) is efficacious in patients
      who have undergone Billroth II gastroenterostomies, but the success rate
      decreases in patients who also have experienced Braun anastomoses. There are
      currently no reports describing the preferred enterography route for cannulation
      in these patients. We first review the patient's previous surgery records, which
      most often indicate that the efferent loop is at the greater curvature of the
      stomach. We recommend extending the duodenoscope along the greater curvature of
      the stomach and then advancing it through the "lower entrance" at the site of the
      gastrojejunal anastomosis, along the efferent loop, and through the "middle
      entrance" at the site of the Braun anastomosis to reach the papilla of Vater. Ten
      patients who had each undergone Billroth II gastroenterostomy and Braun
      anastomosis between January 2009 and December 2011 were included in our study.
      The overall success rate of enterography was 90% for the patients who had
      undergone Billroth II gastroenterostomy and Braun anastomosis, and the
      therapeutic success rate was 80%. We believe that this enterography route for
      ERCP is optimal for a patient who has had Billroth II gastroenterostomy and Braun
      anastomosis and helps to increase the success rate of the procedure.

PMID- 24574732
TI  - A completely isolated intestinal duplication cyst mimicking ovarian cyst torsion
      in an adult.
AB  - Intestinal duplications are rare congenital anomalies that can occur anywhere in
      the gastrointestinal tract. They are most commonly located in the ileum and are
      usually detected in infancy or early childhood. Duplicated segments are usually
      firmly attached to and sometimes communicate with the normal gastrointestinal
      tract. Rarely, intestinal duplications are completely isolated, thus not
      associated at all with any part of the gastrointestinal tract. Such duplications
      do not share a common blood supply with the adjacent normal intestinal segment,
      unlike the usual form of duplication, but rather have a separate vascular
      pedicle. Reports of completely isolated duplication cysts in adults are extremely
      rare; we found only five such reports in the English-language medical literature.
      Here, we report a case of a completely isolated duplication cyst 12 cm long in an
      adult female. The cyst had no connection to any part of the intestinal tract and
      had a dedicated vascular pedicle. 

PMID- 24574734
TI  - Fecal calprotectin in coeliac disease.
AB  - We would like to share with the readers the results of our experience in 50
      celiac disease (CD) patients, enrolled between September 2012 and April 2013, who
      were referred to our third-level CD Unit. The fecal calprotectin (FC)
      concentration of 50 adults with newly diagnosed CD was compared to that of a
      control group of 50 healthy subjects. FC level was determined by enzyme linked
      immunosorbent assay with diagnostic cut-off of 75 MUg/g. In addition, we tried to
      correlate the FC level with symptoms, histological severity of CD (Marsh grade)
      and level of tissue transglutaminase antibodies (aTg) in CD patients. Finally, FC
      level was increased in five CD patients and in four controls (10% vs 8%, P = NS);
      mean FC concentration of patients and controls were 57.7 (SD +/- 29.1) and 45.1
      (SD +/- 38.4) respectively. Furthermore, no significant correlation was seen
      between FC levels and symptoms/Marsh grade/aTg. The five CD patients did not show
      inflammatory lesions (e.g., ulcers, erosions) at upper endoscopy. The four
      healthy controls with positive FC were followed-up for further six months; in
      this observational period they did not show clinical signs of any underlying
      disease. On these bases, we think that FC is not able to investigate the
      subclinical inflammatory changes of active CD and FC should be considered a
      useless tool in the diagnostic work-up of uncomplicated CD but it should be
      accompanied by aTg when ruling out organic disease in patients with irritable
      bowel syndrome.

PMID- 24574736
TI  - Helicobacter pylori gamma-glutamyl transpeptidase and its pathogenic role.
AB  - Helicobacter pylori (H. pylori) gamma-glutamyl transpeptidase (GGT) is a
      bacterial virulence factor that converts glutamine into glutamate and ammonia,
      and converts glutathione into glutamate and cysteinylglycine. H. pylori GGT
      causes glutamine and glutathione consumption in the host cells, ammonia
      production and reactive oxygen species generation. These products induce cell
      cycle arrest, apoptosis, and necrosis in gastric epithelial cells. H. pylori GGT
      may also inhibit apoptosis and induce gastric epithelial cell proliferation
      through the induction of cyclooxygenase-2, epidermal growth factor-related
      peptides, inducible nitric oxide synthase and interleukin-8. H. pylori GGT
      induces immune tolerance through the inhibition of T cell-mediated immunity and
      dendritic cell differentiation. The effect of GGT on H. pylori colonization and
      gastric persistence are also discussed. 

PMID- 24574735
TI  - Helicobacter pylori and autoimmune disease: cause or bystander.
AB  - Helicobacter pylori (H. pylori) is the main cause of chronic gastritis and a
      major risk factor for gastric cancer. This pathogen has also been considered a
      potential trigger of gastric autoimmunity, and in particular of autoimmune
      gastritis. However, a considerable number of reports have attempted to link H.
      pylori infection with the development of extra-gastrointestinal autoimmune
      disorders, affecting organs not immediately relevant to the stomach. This review
      discusses the current evidence in support or against the role of H. pylori as a
      potential trigger of autoimmune rheumatic and skin diseases, as well as organ
      specific autoimmune diseases. We discuss epidemiological, serological,
      immunological and experimental evidence associating this pathogen with autoimmune
      diseases. Although over one hundred autoimmune diseases have been investigated in
      relation to H. pylori, we discuss a select number of papers with a larger
      literature base, and include Sjogrens syndrome, rheumatoid arthritis, systemic
      lupus erythematosus, vasculitides, autoimmune skin conditions, idiopathic
      thrombocytopenic purpura, autoimmune thyroid disease, multiple sclerosis,
      neuromyelitis optica and autoimmune liver diseases. Specific mention is given to
      those studies reporting an association of anti-H. pylori antibodies with the
      presence of autoimmune disease-specific clinical parameters, as well as those
      failing to find such associations. We also provide helpful hints for future
      research. 

PMID- 24574737
TI  - Impairment of ghrelin synthesis in Helicobacter pylori-colonized stomach: new
      clues for the pathogenesis of H. pylori-related gastric inflammation.
AB  - Ghrelin, the ligand of growth hormone secretagogue receptor 1a, takes part in
      several functions of the digestive system, including regulation of appetite,
      energy homeostasis, gastric acid secretion and motility. Ghrelin has also
      immunoregulatory properties and is supposed to inhibit some inflammatory pathways
      that can mediate gastric damage. Interestingly, ghrelin synthesis is reduced in
      the gastric mucosa of patients with Helicobacter pylori (H. pylori) infection, a
      worldwide condition inducing a T helper (Th)1/Th17 cell response-driven
      gastritis, which may evolve towards gastric atrophy and cancer. In this article,
      we review the available data on the expression of ghrelin in H. pylori infection
      and discuss how the defective ghrelin synthesis may contribute to sustain the
      ongoing inflammatory response in this disease. 

PMID- 24574738
TI  - Helicobacter pylori infection in obesity and its clinical outcome after bariatric
      surgery.
AB  - The present review summarizes the prevalence and active clinical problems in
      obese patients with Helicobacter pylori (H. pylori) infection, as well as the
      outcomes after bariatric surgery in this patient population. The involvement of
      H. pylori in the pathophysiology of obesity is still debated. It may be that the
      infection is protective against obesity, because of the gastritis-induced
      decrease in production and secretion of the orexigenic hormone ghrelin. However,
      recent epidemiological studies have failed to show an association between H.
      pylori infection and reduced body mass index. H. pylori infection might represent
      a limiting factor in the access to bariatric bypass surgery, even if high-quality
      evidence indicating the advantages of preoperative H. pylori screening and
      eradication is lacking. The clinical management of infection is complicated by
      the lower eradication rates with standard therapeutic regimens reported in obese
      patients than in the normal-weight population. Prospective clinical studies to
      ameliorate both H. pylori eradication rates and control the clinical outcomes of
      H. pylori infection after different bariatric procedures are warranted. 

PMID- 24574739
TI  - Helicobacter pylori and pregnancy-related disorders.
AB  - Helicobacter pylori (H. pylori) infection is investigated in gastric diseases
      even during pregnancy. In particular, this Gram-negative bacterium seems to be
      associated with hyperemesis gravidarum, a severe form of nausea and vomiting
      during pregnancy. During the last decade, the relationship among H. pylori and
      several extra-gastric diseases strongly emerged in literature. The correlation
      among H. pylori infection and pregnancy-related disorders was mainly focused on
      iron deficiency anemia, thrombocytopenia, fetal malformations, miscarriage, pre
      eclampsia and fetal growth restriction. H. pylori infection may have a role in
      the pathogenesis of various pregnancy-related disorders through different
      mechanisms: depletion of micronutrients (iron and vitamin B12) in maternal anemia
      and fetal neural tube defects; local or systemic induction of pro-inflammatory
      cytokines release and oxidative stress in gastrointestinal disorders and pre
      eclampsia; cross-reaction between specific anti-H. pylori antibodies and antigens
      localized in placental tissue and endothelial cells (pre-eclampsia, fetal growth
      restriction, miscarriage). Since H. pylori infection is most likely acquired
      before pregnancy, it is widely believed that hormonal and immunological changes
      occurring during pregnancy could activate latent H. pylori with a negative impact
      not only on maternal health (nutritional deficiency, organ injury, death), but
      also on the fetus (insufficient growth, malformation, death) and sometime
      consequences can be observed later in life. Another important issue addressed by
      investigators was to determine whether it is possible to transmit H. pylori
      infection from mother to child and whether maternal anti-H. pylori antibodies
      could prevent infant's infection. Studies on novel diagnostic and therapeutic
      methods for H. pylori are no less important, since these are particularly
      sensitive topics in pregnancy conditions. It could be interesting to study the
      possible correlation between H. pylori infection and other pregnancy-related
      diseases of unknown etiology, such as gestational diabetes mellitus, obstetric
      cholestasis and spontaneous preterm delivery. Since H. pylori infection is
      treatable, the demonstration of its causative role in pregnancy-related disorders
      will have important social-economic implications.

PMID- 24574740
TI  - Eradication of Helicobacter pylori infection: which regimen first?
AB  - Helicobacter pylori (H. pylori) is a well-known human pathogen that plays an
      essential role in the pathogenesis of chronic gastritis, peptic ulcer disease,
      and gastric malignancies. Although H. pylori is susceptible to several
      antimicrobials, this infection has proven challenging to cure because of the
      increasing prevalence of bacterial strains that are resistant to the most
      commonly used antimicrobials, particularly clarithromycin. An effective (i.e., >
      90%) first-line therapy is mandatory for avoiding supplementary treatments and
      testing, and more importantly for preventing the development of secondary
      resistance. This study reviews the recent literature on first-line therapies for
      H. pylori. The eradication rates following standard triple therapy (a proton pump
      inhibitor plus amoxicillin and clarithromycin) for H. pylori infection are
      declining worldwide. Several first-line strategies have been proposed to increase
      the eradication rate, including extending the treatment duration to 14 d, the use
      of a four-drug regimen (bismuth-containing quadruple, sequential, and concomitant
      treatments), and the use of novel antibiotics, such as fluoroquinolones. However,
      the efficacy of these regimens is controversial. A first-line eradication regimen
      should be based on what works best in a defined geographical area and must take
      into account the prevalence of antimicrobial resistance in that region. 

PMID- 24574741
TI  - Probiotics for the treatment of Helicobacter pylori infection in children.
AB  - The combination of a proton pump inhibitor and two antibiotics (clarithromycin
      plus amoxicillin or metronidazole) has been the recommended first-line therapy
      since the first guidelines for Helicobacter pylori (H. pylori) infection in
      children were published. In recent years, the success of eradication therapies
      has declined, in part due to the development of H. pylori resistant strains.
      Alternative anti-H. pylori treatments are currently becoming more popular than
      the traditional eradication methods. Components that may be used either as a
      monotherapy or, in combination with antimicrobials, resulting in a more effective
      anti-H. pylori therapy have been investigated in depth by several researchers.
      One of the potential therapies is probiotic cultures; promising results have been
      observed in initial studies with numerous probiotic strains. Nevertheless, many
      questions remain unanswered. In this article, we comprehensively review the
      possible mechanisms of action of probiotics on H. pylori infection, and present
      the results of published studies using probiotics as possible agents to control
      H. pylori infection in children. The effect of the addition of probiotics to the
      standard H. pylori eradication therapy for the prevention of antibiotic
      associated side-effects is also discussed. 

PMID- 24574743
TI  - Helicobacter pylori: future perspectives in therapy reflecting three decades of
      experience.
AB  - The rising prevalence of antibiotic resistance has created a need to reassess the
      established Helicobacter pylori (H. pylori) eradication protocols, and to develop
      new ones. Various bacterial and host factors are evaluated, and their
      contribution to eradication failure is estimated. For a long time being
      considered the cornerstone eradication scheme, the standard triple therapy has
      been replaced with novel, more efficient regimens, namely sequential and
      concomitant, along with the emergence of a new design of bismuth quadruple
      therapy. A rescue levofloxacin based regimen has overcome the fear of therapy
      failure due to higher prevalence of dual resistant (clarithromycin and
      metronidazole) H. pylori. Culture-free and efficient susceptibility test are
      reestablishing the concept of tailored therapy, making eradication success close
      to originally desirable rates. Alleviating therapy side effects and improving
      patient compliance are as important as choosing appropriate eradication schemes,
      so various probiotic compound supplements are taken into consideration. Finally,
      we summarize the emerging efforts and obstacles in creating efficient H. pylori
      vaccine. 

PMID- 24574744
TI  - Helicobacter pylori-negative, non-steroidal anti-inflammatory drug: negative
      idiopathic ulcers in Asia.
AB  - Since the discovery of Helicobacter pylori (H. pylori) infection in the stomach,
      the bacteria infection and non-steroidal anti-inflammatory drugs (NSAIDs) use had
      been considered to be the 2 main causes of peptic ulcers. However, there have
      been recent reports of an increase in the proportion of peptic ulcers without
      these known risk factors; these are termed idiopathic peptic ulcers. Such trend
      was firstly indicated in 1990s from some reports in North America. In Asia,
      numerous studies reported that idiopathic ulcers accounted for a small percentage
      of all ulcers in the 1990s, but in the 2000s, multiple studies reported that the
      proportion of idiopathic ulcers had reached 10%-30%, indicating that the
      incidence of idiopathic ulcers in Asia has also been rising in recent years.
      While a decline in H. pylori infection rates of general population in Asia is
      seen as the main reason for the increased incidence of idiopathic ulcers, it is
      also possible that the absolute number of idiopathic ulcer cases has increased.
      Advanced age, serious systemic complication, and psychological stress are
      considered to be the potential risk factors for idiopathic ulcers. Management of
      idiopathic ulcers is challenging, at present, because there is no effective
      preventative measure against recurrence in contrast with cases of H. pylori
      positive ulcers and NSAIDs-induced ulcers. As it is expected that H. pylori
      infection rates in Asia will decline further in the future, measures to treat
      idiopathic ulcers will also likely become more important. 

PMID- 24574745
TI  - Helicobacter pylori-associated immune thrombocytopenia: clinical features and
      pathogenic mechanisms.
AB  - Immune thrombocytopenia (ITP) is an autoimmune disease mediated by anti-platelet
      autoantibodies. There is growing evidence that the eradication of Helicobacter
      pylori (H. pylori) effectively increases platelet count in a considerable
      proportion of ITP patients infected with this bacterium. In the majority of ITP
      patients responding to H. pylori eradication therapy, the anti-platelet
      autoantibody response is completely resolved with no relapse for more than 7
      years, indicating that the disease is cured. Therefore, adult patients with
      suspected ITP should be examined for H. pylori infection, and eradication therapy
      is recommended if the infection is present. Notably, however, the efficacy of H.
      pylori eradication therapy in ITP patients varies widely among countries, with a
      higher response rate in Japan compared with the United States and European
      countries other than Italy. The pathogenesis of H. pylori-associated ITP is still
      uncertain, although the mechanisms are known to involve multiple factors. H.
      pylori may modulate the Fcgamma-receptor balance of monocytes/macrophages in
      favor of activating Fcgamma receptors, and H. pylori components may mimic the
      molecular makeup of platelet antigens. Further studies of the pathogenic process
      of H. pylori-associated ITP may be useful for the development of new therapeutic
      strategies for ITP. 

PMID- 24574742
TI  - Role of Helicobacter pylori in gastric mucosa-associated lymphoid tissue
      lymphomas.
AB  - Mucosa-associated lymphoid tissue (MALT) lymphoma is an indolent extranodal
      marginal zone B-cell lymphoma, originating in acquired MALT that is induced in
      mucosal barriers as part of a normal adaptive immune response to a chronic
      immunoinflammatory stimulus, most notably chronic infection by Helicobacter
      pylori (H. pylori). This antigenic stimulation initially leads to lymphoid
      hyperplasia; the acquisition of additional genetic aberrations culminates in the
      activation of intracellular survival pathways, with disease progression due to
      proliferation and resistance to apoptosis, and the emergence of a malignant
      clone. There are descriptions of MALT lymphomas affecting practically every organ
      and system, with a marked geographic variability partially attributable to the
      epidemiology of the underlying risk factors; nevertheless, the digestive system
      (and predominantly the stomach) is the most frequently involved location,
      reflecting the gastrointestinal tract's unique characteristics of contact with
      foreign antigens, high mucosal permeability, large extension and intrinsic
      lymphoid system. While early-stage gastric MALT lymphoma can frequently regress
      after the therapeutic reversal of the chronic immune stimulus through antibiotic
      eradication of H. pylori infection, the presence of immortalizing genetic
      abnormalities, of advanced disease or of eradication-refractoriness requires a
      more aggressive approach which is, presently, not consensual. The fact that MALT
      lymphomas are rare neoplasms, with a worldwide incidence of 1-1.5 cases per 105
      population, per year, limits the ease of accrual of representative series of
      patients for robust clinical trials that could sustain informed evidence-based
      therapeutic decisions to optimize the quality of patient care.

PMID- 24574746
TI  - Efficacy of fermented milk and whey proteins in Helicobacter pylori eradication:
      a review.
AB  - Helicobacter pylori (H. pylori) eradication is considered a necessary step in the
      management of peptic ulcer disease, chronic gastritis, gastric adenocarcinoma and
      mucosa associated lymphoid tissue lymphoma. Standard triple therapy eradication
      regimens are inconvenient and achieve unpredictable and often poor results.
      Eradication rates are decreasing over time with increase in antibiotic
      resistance. Fermented milk and several of its component whey proteins have
      emerged as candidates for complementary therapy. In this context the current
      review seeks to summarize the current evidence available on their role in H.
      pylori eradication. Pertinent narrative/systematic reviews, clinical trials and
      laboratory studies on individual components including fermented milk, yogurt,
      whey proteins, lactoferrin, alpha-lactalbumin (alpha-LA), glycomacropeptide and
      immunoglobulin were comprehensively searched and retrieved from Medline, Embase,
      Scopus, Cochrane Controlled Trials Register and abstracts/proceedings of
      conferences up to May 2013. A preponderance of the evidence available on
      fermented milk-based probiotic preparations and bovine lactoferrin suggests a
      beneficial effect in Helicobacter eradication. Evidence for alpha-LA and
      immunoglobulins is promising while that for glycomacropeptide is preliminary and
      requires substantiation. The magnitude of the potential benefit documented so far
      is small and the precise clinical settings are ill defined. This restricts the
      potential use of this group as a complementary therapy in a nutraceutical setting
      hinging on better patient acceptability/compliance. Further work is necessary to
      identify the optimal substrate, fermentation process, dose and the ideal clinical
      setting (prevention/treatment, first line therapy/recurrence,
      symptomatic/asymptomatic, gastritis/ulcer diseases etc.). The potential of this
      group in high antibiotic resistance or treatment failure settings presents
      interesting possibilities and deserves further exploration. 

PMID- 24574747
TI  - Solitary rectal ulcer syndrome: clinical features, pathophysiology, diagnosis and
      treatment strategies.
AB  - Solitary rectal ulcer syndrome (SRUS) is an uncommon benign disease,
      characterized by a combination of symptoms, clinical findings and histological
      abnormalities. Ulcers are only found in 40% of the patients; 20% of the patients
      have a solitary ulcer, and the rest of the lesions vary in shape and size, from
      hyperemic mucosa to broad-based polypoid. Men and women are affected equally,
      with a small predominance in women. SRUS has also been described in children and
      in the geriatric population. Clinical features include rectal bleeding, copious
      mucus discharge, prolonged excessive straining, perineal and abdominal pain,
      feeling of incomplete defecation, constipation, and rarely, rectal prolapse. This
      disease has well-described histopathological features such as obliteration of the
      lamina propria by fibrosis and smooth muscle fibers extending from a thickened
      muscularis mucosa to the lumen. Diffuse collage deposition in the lamina propria
      and abnormal smooth muscle fiber extensions are sensitive markers for
      differentiating SRUS from other conditions. However, the etiology remains
      obscure, and the condition is frequently associated with pelvic floor disorders.
      SRUS is difficult to treat, and various treatment strategies have been advocated,
      ranging from conservative management to a variety of surgical procedures. The aim
      of the present review is to summarize the clinical features, pathophysiology,
      diagnostic methods and treatment strategies associated with SRUS. 

PMID- 24574748
TI  - Transarterial chemoembolization in Barcelona Clinic Liver Cancer Stage 0/A
      hepatocellular carcinoma.
AB  - AIM: To evaluate the clinical characteristics of patients with Barcelona Clinic
      Liver Cancer (BCLC) stage 0 and A hepatocellular carcinoma (HCC) after
      transarterial chemoembolization (TACE). METHODS: Between January 2001 and
      September 2011, 129 patients with BCLC stage 0 and stage A HCC who underwent TACE
      were retrospectively enrolled. Patient characteristics, routine computed
      tomography and TACE findings, survival time and 1-, 5-, and 10-year survival
      rates, risk factors for mortality, and survival rates according to the number of
      risk factors were assessed. RESULTS: The mean size of HCC tumors was 2.4 +/- 1.1
      cm, and the mean number of TACE procedures performed was 2.5 +/- 2.1. The mean
      overall survival time and 1-, 5-, and 10-year survival rates were 80.6 +/- 4.9 mo
      and 91%, 63% and 49%, respectively. In the Cox regression analysis, a Child-Pugh
      score > 5 (P = 0.005, OR = 3.86), presence of arterio-venous shunt (P = 0.032, OR
      = 4.41), amount of lipiodol used (> 7 mL; P = 0.013, OR = 3.51), and female
      gender (P = 0.008, OR = 3.47) were risk factors for mortality. The 1-, 5-, and 10
      year survival rates according to the number of risk factors present were 96%, 87%
      and 87% (no risk factors), 89%, 65%, and 35% (1 risk factor), 96%, 48% and
      unavailable (2 risk factors), and 63%, 17%, and 0% (3 risk factors), respectively
      (P < 0.001). CONCLUSION: TACE may be used as curative-intent therapy in patients
      with BCLC stage 0 and stage A HCC. The Child-Pugh score, arterio-venous shunt,
      amount of lipiodol used, and gender were related to mortality after TACE.

PMID- 24574749
TI  - Epidermal growth factor upregulates Skp2/Cks1 and p27(kip1) in human extrahepatic
      cholangiocarcinoma cells.
AB  - AIM: To evaluate the expression status of S-phase kinase-associated protein 2
      (Skp2)/cyclin-dependent kinases regulatory subunit 1 (Cks1) and p27(kip1), and
      assess the prognostic significance of Skp2/Cks1 expression with p27(kip1) in
      patients with extrahepatic cholangiocarcinoma. METHODS: Seventy-six patients who
      underwent curative resection for histologically confirmed extrahepatic
      cholangiocarcinoma at our institution from December 1994 to March 2008 were
      enrolled. Immunohistochemical staining for Skp2, Cks1, p27(kip1), and Ki67, along
      with other relevant molecular biologic experiments, were performed. RESULTS: By
      Cox regression analyses, advanced age (> 65 years), advanced AJCC tumor stage,
      poorly differentiated histology, and higher immunostaining intensity of Skp2 were
      identified as independent prognostic factors in patients with extrahepatic
      cholangiocarcinoma. Exogenous epidermal growth factor (EGF, especially 0.1-10
      ng/mL) significantly increased the proliferation indices by MTT assay and the
      mRNA levels of Skp2/Cks1 and p27(kip1) in SNU-1196, SNU-1079, and SNU-245 cells.
      The protein levels of Skp2/Cks1 (from nuclear lysates) and p27(kip1) (from
      cytosolic lysate) were also significantly increased in these cells. There were
      significant reductions in the protein levels of Skp2/Cks1 and p27(kip1) (from
      nuclear lysate) after the treatment of LY294002. By chromatin immunoprecipitation
      assay, we found that E2F1 transcription factor directly binds to the promoter
      site of Skp2. CONCLUSION: Higher immunostaining intensity of Skp2/Cks1 was an
      independent prognostic factor for patients with extrahepatic cholangiocarcinoma.
      EGF upregulates the mRNA and protein levels of Skp2/Cks1 and p27(kip1) via the
      PI3K/Akt pathway and direct binding of E2F1 transcription factor with the Skp2
      promoter.

PMID- 24574750
TI  - Shunting branch of portal vein and stent position predict survival after
      transjugular intrahepatic portosystemic shunt.
AB  - AIM: To evaluate the effect of the shunting branch of the portal vein (PV) (left
      or right) and the initial stent position (optimal or suboptimal) of a
      transjugular intrahepatic portosystemic shunt (TIPS). METHODS: We retrospectively
      reviewed 307 consecutive cirrhotic patients who underwent TIPS placement for
      variceal bleeding from March 2001 to July 2010 at our center. The left PV was
      used in 221 patients and the right PV in the remaining 86 patients. And, 224 and
      83 patients have optimal stent position and sub-optimal stent positions,
      respectively. The patients were followed until October 2011 or their death.
      Hepatic encephalopathy, shunt dysfunction, and survival were evaluated as
      outcomes. The difference between the groups was compared by Kaplan-Meier
      analysis. A Cox regression model was employed to evaluate the predictors.
      RESULTS: Among the patients who underwent TIPS to the left PV, the risk of
      hepatic encephalopathy (P = 0.002) and mortality were lower (P < 0.001) compared
      to those to the right PV. Patients who underwent TIPS with optimal initial stent
      position had a higher primary patency (P < 0.001) and better survival (P = 0.006)
      than those with suboptimal initial stent position. The shunting branch of the
      portal vein and the initial stent position were independent predictors of hepatic
      encephalopathy and shunt dysfunction after TIPS, respectively. And, both were
      independent predictors of survival. CONCLUSION: TIPS placed to the left portal
      vein with optimal stent position may reduce the risk of hepatic encephalopathy
      and improve the primary patency rates, thereby prolonging survival.

PMID- 24574751
TI  - Predictors of survival in patients with established cirrhosis and hepatocellular
      carcinoma treated with sorafenib.
AB  - AIM: To investigate in greater detail the efficacy and safety of sorafenib for
      the treatment of hepatocellular carcinoma (HCC) in patients with established
      cirrhosis. METHODS: From October 2009 to July 2012 patients with an established
      diagnosis of cirrhosis and HCC treated with sorafenib were consecutively
      enrolled. According to the Barcelona Clinic Liver Cancer (BCLC) classification,
      patients were in the advanced stage (BCLC-C) or in the intermediate stage (BCLC
      B) but unfit or unresponsive to other therapeutic strategies. Treatment was
      evaluated performing a 4-phase computed tomography or magnetic resonance imaging
      scan every 2-3 mo, and analyzed according to the modified Response Evaluation
      Criteria in Solid Tumors. Sorafenib was administered at 800 mg/d, until
      radiological progression or occurrence of unacceptable adverse events (AEs).
      Univariate and multivariate analyses identified predictors of 16-wk clinical
      benefit and overall survival. RESULTS: Forty-four patients were enrolled, 15 had
      intermediate HCC and 14 a Child-Pugh score of B7. AEs caused treatment
      interruption in 19 patients (43%), and median treatment duration was shorter in
      this subset (5 wk vs 19 wk, P < 0.001) and in the BCLC-C subgroup (13 wk vs 40
      wk, P = 0.015). No significant differences in the reason for treatment
      interruption or in treatment duration were found comparing patients in Child-Pugh
      class A vs B or in patients older or younger than 70 years. After 16 wk of
      treatment, 18 patients (41%) had stable disease or partial response. Patients
      with viral infection or BCLC-C were at higher risk of disease progression. ECOG,
      extrahepatic spread, macrovascular invasion, alpha-fetoprotein or alkaline
      phosphatase levels at admission were independent predictors of overall survival.
      CONCLUSION: In patients with cirrhosis and HCC treated with sorafenib, AEs are a
      common cause of early treatment withdrawal. Vascular invasion and extrahepatic
      spread condition early response to treatment and survival. Baseline biochemical
      parameters may be helpful to identify patients at higher risk of shorter overall
      survival.

PMID- 24574752
TI  - Bortezomib effect on E2F and cyclin family members in human hepatocellular
      carcinoma cell lines.
AB  - AIM: To evaluate the effects of the proteasome inhibitor bortezomib (BZB) on E2Fs
      and related genes in hepatocellular carcinoma (HCC) cells. METHODS: The mRNA
      levels of the E2F family members (pro-proliferative: E2F1-3 and anti
      proliferative: E2F4-8) and of their related genes cyclins and cyclin-dependent
      kinases (cdks) were evaluated in two HCC cell lines following a single BZB
      administration. mRNA levels of the epithelial-mesenchymal transition (EMT) genes
      were also measured in both cell lines after BZB treatment. The BZB concentration
      (40 nmol/L) used was chosen to stay well below the maximal amount/cm2 recommended
      for in vivo application, and 2 d incubation was chosen as this time point has
      been found optimal to detect BZB effects in our previous studies. The HCC cell
      lines, HepG2 and JHH6, were chosen as they display different phenotypes,
      hepatocyte-like for HepG2 and undifferentiated for JHH6, thus representing an in
      vitro model of low and high aggressive forms of HCC, respectively. The mRNA
      levels of the target genes were measured by two-color microarray-based gene
      expression analysis, performed according to Agilent Technologies protocol and
      using an Agilent Scan B. For the E2F family members, mRNA levels were quantified
      by real-time reverse transcription polymerase chain reaction (RT-PCR). Using
      small interfering RNA's, the effects of E2F8 depletion on cell number was also
      evaluated. RESULTS: After BZB treatment, microarray analysis of the
      undifferentiated JHH6 revealed a significant decrease in the expression of the
      pro-proliferative E2F member E2F2. Quantitative RT-PCR data were in keeping with
      the microarray analysis, and showed a significant increase and decrease in E2F8
      and E2F2 mRNA levels, respectively. In contrast, BZB treatment of the hepatocyte
      like HCC cell line HepG2 had a significant impact on mRNA levels of 5 of the 8
      E2F members. In particular, mRNA levels of the pro-proliferative E2F members
      E2F1, E2F2, and of the anti-proliferative member E2F8, decreased over 80%.
      Notably, a reduction in E2F8 expression in HepG2 and JHH6 cells following siRNA
      treatment had no impact on cell proliferation. As observed with JHH6, BZB
      treatment of HepG2 cells induced a significant increase in mRNA levels of an anti
      proliferative E2F member, E2F6 in this case. As was observed with E2F's, more
      dramatic changes in mRNA levels of the E2F related genes cyclins and Cdks and EMT
      genes were observed after BZB treatment of HepG2 compared to JHH6. CONCLUSION:
      The differential expression of E2Fs and related genes induced by BZB in diverse
      HCC cell phenotypes contribute to bortezomib's mechanism of action in
      hepatocellular carcinoma.

PMID- 24574753
TI  - Systematic review: laparoscopic fundoplication for gastroesophageal reflux
      disease in partial responders to proton pump inhibitors.
AB  - AIM: To assess laparoscopic fundoplication (LF) in partial responders to proton
      pump inhibitors (PPIs) for gastroesophageal reflux disease (GERD). METHODS: We
      systematically searched PubMed and Embase (1966-Dec 2011) for articles reporting
      data on LF efficacy in partial responders. Due to a lack of randomized controlled
      trials, observational studies were included. Of 558 articles screened, 17 were
      eligible for inclusion. Prevalence data for individual symptoms were collated
      across studies according to mutually compatible time points (before and/or after
      LF). Where suitable, prevalence data were presented as percentage of patients
      reporting symptoms of any frequency or severity. RESULTS: Due to a lack of
      standardized reporting of symptoms, the proportion of patients experiencing
      symptoms was recorded across studies where possible. After LF, the proportion of
      partial responders with heartburn was reduced from 93.1% (5 studies) to 3.8% (5
      studies), with similar results observed for regurgitation [from 78.4% (4 studies)
      to 1.9% (4 studies)]. However, 10 years after LF, 35.8% (2 studies) of partial
      responders reported heartburn and 29.1% (1 study) reported regurgitation. The
      proportion using acid-suppressive medication also increased, from 8.8% (4
      studies) in the year after LF to 18.2% (2 studies) at 10 years. In the only study
      comparing partial responders to PPI therapy with complete responders, higher
      symptom scores and more frequent acid-suppressive medication use were seen in
      partial responders after LF. CONCLUSION: GERD symptoms improve after LF, but
      subsequently recur, and acid-suppressive medication use increases. LF may be less
      effective in partial responders than in complete responders.

PMID- 24574754
TI  - Epidemiological and clinical characteristics of inflammatory bowel diseases in
      Cairo, Egypt.
AB  - AIM: To study the natural history, patterns and clinical characteristics of
      inflammatory bowel diseases (IBD) in Egypt. METHODS: We designed a case-series
      study in the gastroenterology centre of the Internal Medicine department of Cairo
      University, which is a tertiary care referral centre in Egypt. We included all
      patients in whom the diagnosis of ulcerative colitis (UC) or Crohn's disease (CD)
      was confirmed by clinical, laboratory, endoscopic, histological and/or
      radiological criteria over the 15 year period from 1995 to 2009, and we studied
      their sociodemographic and clinical characteristics. Endoscopic examinations were
      performed by 2 senior experts. This hospital centre serves patients from Cairo,
      as well as patients referred from all other parts of Egypt. Our centre received
      24156 patients over the described time period for gastro-intestinal consultations
      and/or interventions. RESULTS: A total of 157 patients with established IBD were
      included in this study. Of these, 135 patients were diagnosed with UC (86% of the
      total), and 22 patients, with CD (14% of the total). The mean ages at diagnosis
      were 27.3 and 29.7, respectively. Strikingly, we noticed a marked increase in the
      frequency of both UC and CD diagnoses during the most recent 10 years of the 15
      year period studied. Regarding the gender distribution, the male:female ratio was
      1:1.15 for UC and 2.6:1 for CD. The mean duration of follow up for patients with
      UC was 6.2 +/- 5.18 years, while the mean duration of follow up for patients with
      CD was 5.52 +/- 2.83 years. For patients with UC we found no correlation between
      the severity of the disease and the presence of extraintestinal manifestations.
      Eleven patients had surgical interventions during the studied years: 4 cases of
      total colectomy and 7 cases of anal surgery. CONCLUSION: We observed a ratio of
      6:1 for UC to CD in our series. The incidence of IBD seems to be rising in Egypt.

PMID- 24574755
TI  - Impairment of secondary peristalsis in Barrett's esophagus by transnasal
      endoscopy-based testing.
AB  - AIM: To investigate dysfunctions in esophageal peristalsis and sensation in
      patients with Barrett's esophagus following acid infusion using endoscopy-based
      testing. METHODS: First, physiological saline was infused into the esophagus of
      five healthy subjects, at a rate of 10 mL/min for 10 min, followed by infusion of
      HCl. Esophageal contractions were analyzed to determine whether the contractions
      observed by endoscopy and ultrasonography corresponded to the esophageal
      peristaltic waves diagnosed by manometry. Next, using nasal endoscopy, esophageal
      sensations and contractions were investigated in patients with, as well as
      controls without, Barrett's esophagus using the same infusion protocol. RESULTS:
      All except one of the propulsive contractions identified endoscopically were
      recorded as secondary peristaltic waves by manometry. Patients with long segment
      Barrett's esophagus (LSBE) tended to have a shorter lag time than the control
      group, although the difference did not reach statistical significance (88 +/- 54
      s vs 162 +/- 150 s respectively, P = 0.14). Furthermore, patients with LSBE had
      significantly fewer secondary contractions following the infusion of both saline
      and HCl than did either the control group or patients with short segment
      Barrett's esophagus (4.1 +/- 1.2 vs 8.0 +/- 2.8, P < 0.001 and 7.3 +/- 3.2, P <
      0.01, respectively, following saline infusion; 5.3 +/- 1.2 vs 8.4 +/- 2.4 and 8.1
      +/- 2.9 respectively, P < 0.01 for both, following infusion of HCl). CONCLUSION:
      Using nasal endoscopy and a simple acid-perfusion study, we were able to
      demonstrate disorders in secondary peristalsis in patients with LSBE.

PMID- 24574756
TI  - Distance management of inflammatory bowel disease: systematic review and meta
      analysis.
AB  - AIM: To review the effectiveness of distance management methods in the management
      of adult inflammatory bowel disease (IBD) patients. METHODS: A systematic review
      and meta-analysis of randomized controlled trials comparing distance management
      and standard clinic follow-up in the management of adult IBD patients. Distance
      management intervention was defined as any remote management method in which
      there is a patient self-management component whereby the patient interacts
      remotely via a self-guided management program, electronic interface, or self
      directs open access to clinic follow up. The search strategy included electronic
      databases (Medline, PubMed, CINAHL, The Cochrane Central Register of Controlled
      Trials, EMBASE, KTPlus, Web of Science, and SCOPUS), conference proceedings, and
      internet search for web publications. The primary outcome was the mean difference
      in quality of life, and the secondary outcomes included mean difference in
      relapse rate, clinic visit rate, and hospital admission rate. Study selection,
      data extraction, and risk of bias assessment were completed by two independent
      reviewers. RESULTS: The search strategy identified a total of 4061 articles, but
      only 6 randomized controlled trials met the inclusion and exclusion criteria for
      the systematic review and meta-analysis. Three trials involved telemanagement,
      and three trials involved directed patient self-management and open access
      clinics. The total sample size was 1463 patients. There was a trend towards
      improved quality of life in distance management patients with an end IBDQ quality
      of life score being 7.28 (95%CI: -3.25-17.81) points higher than standard clinic
      follow-up. There was a significant decrease in the clinic visit rate among
      distance management patients mean difference -1.08 (95%CI: -1.60--0.55), but no
      significant change in relapse rate or hospital admission rate. CONCLUSION:
      Distance management of IBD significantly decreases clinic visit utilization, but
      does not significantly affect relapse rates or hospital admission rates.

PMID- 24574758
TI  - A case report of anaplastic carcinoma of the pancreas with remarkable intraductal
      tumor growth into the main pancreatic duct.
AB  - We herein report a case of anaplastic carcinoma of the pancreas with remarkable
      intraductal tumor growth into the main pancreatic duct. A 76-year-old male was
      referred to our hospital for treatment of a pancreatic tumor. Preoperative
      examinations revealed a poorly defined tumor in the main pancreatic duct in the
      body of the pancreas, accompanied with severe dilatation of the main pancreatic
      duct, which was diagnosed as an intraductal papillary-mucinous neoplasm. We
      performed distal pancreatectomy and splenectomy. The pathological examination
      revealed that the tumor consisted of a mixture of anaplastic carcinoma (giant
      cell type) and adenocarcinoma in the pancreas. There was a papillary projecting
      tumor composed of anaplastic carcinoma in the dilated main pancreatic duct. The
      patient is now receiving chemotherapy because liver metastasis was detected 12 mo
      after surgery. In this case, we could observe a remarkable intraductal tumor
      growth into the main pancreatic duct. We also discuss the pathogenesis and
      characteristics of this rare tumor with specific tumor growth. 

PMID- 24574757
TI  - Remains of the day: biliary complications related to single-port laparoscopic
      cholecystectomy.
AB  - AIM: To assess the rate of bile duct injuries (BDI) and overall biliary
      complications during single-port laparoscopic cholecystectomy (SPLC) compared to
      conventional laparoscopic cholecystectomy (CLC). METHODS: SPLC has recently been
      proposed as an innovative surgical approach for gallbladder surgery. So far, its
      safety with respect to bile duct injuries has not been specifically evaluated. A
      systematic review of the literature published between January 1990 and November
      2012 was performed. Randomized controlled trials (RCT) comparing SPLC versus CLC
      reporting BDI rate and overall biliary complications were included. The quality
      of RCT was assessed using the Jadad score. Analysis was made by performing a meta
      analysis, using Review Manager 5.2. This study was based on the Preferred
      Reporting Items for Systematic reviews and Meta-Analyses guidelines. A
      retrospective study including all retrospective reports on SPLC was also
      performed alongside. RESULTS: From 496 publications, 11 RCT including 898
      patients were selected for meta-analysis. No studies were rated as high quality
      (Jadad score >= 4). Operative indications included benign gallbladder disease
      operated in an elective setting in all studies, excluding all emergency cases and
      acute cholecystitis. The median follow-up was 1 mo (range 0.03-18 mo). The
      incidence of BDI was 0.4% for SPLC and 0% for CLC; the difference was not
      statistically different (P = 0.36). The incidence of overall biliary complication
      was 1.6% for SPLC and 0.5% for CLC, the difference did not reached statistically
      significance (P = 0.21, 95%CI: 0.66-15). Sixty non-randomized trials including
      3599 patients were also analysed. The incidence of BDI reported then was 0.7%.
      CONCLUSION: The safety of SPLC cannot be assumed, based on the current evidence.
      Hence, this new technology cannot be recommended as standard technique for
      laparoscopic cholecystectomy.

PMID- 24574759
TI  - Primary effusion lymphoma-like lymphoma in a patient with inflammatory bowel
      disease.
AB  - A 77-year-old man with inflammatory bowel disease (IBD) and who was treated with
      anti-tumor necrosis factor (TNF), 6-mercaptopurine and corticosteroids, presented
      with primary effusion lymphoma-like lymphoma (PEL-like lymphoma) with massive
      ascites. The patient's clinical course was complicated by acute renal
      insufficiency and hypotension, which led to death within 2 wk. In general,
      patients with IBD may have an increased risk for development of lymphoma, which
      is frequently associated with immunosuppressive and/or anti-TNF antibody
      therapies. PEL is a rare subset of lymphoma localized to serous body cavities,
      lacks tumor mass or nodal involvement, and is associated with infection by human
      herpes virus 8 (HHV-8). Primary neoplastic effusion may also be present in
      patients with large B-cell lymphoma without evidence of human immunodeficiency
      virus or HHV-8 infections. This type of lymphoma is classified as PEL-like
      lymphoma. Both PEL and PEL-like lymphoma types have been reported in patients
      undergoing immunosuppressive therapy, but to the best of our knowledge, the case
      described herein represents the first PEL-like lymphoma occurring in a patient
      with IBD. 

PMID- 24574760
TI  - Malignant extra-gastrointestinal stromal tumor of the pancreas: report of two
      cases and review of the literature.
AB  - Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors that arise from
      the gastrointestinal tract. In rare cases, these tumors are found in intra
      abdominal sites unrelated to the gastrointestinal tract, such as the mesentery,
      omentum and retroperitoneum. However, pancreatic extra-gastrointestinal stromal
      tumors are extremely rare, with only 14 previous cases reported. A 61-year-old
      man with no clinical symptoms had a routine check-up, during which an abdominal
      mass located in the pancreas tail was detected. Abdominal surgery was performed
      with resection of the pancreas tail and the spleen, and he was diagnosed with low
      risk GISTs. Another 60-year-old man with no clinical symptoms underwent Computed
      tomography which revealed a well-demarcated tumor, 6 cm in diameter, in the head
      of the pancreas. He was diagnosed with pancreatic GISTs. Here, we describe two
      rare cases of pancreatic GISTs and review the cases previously reported in the
      literature. 

PMID- 24574761
TI  - Colorectal cancer disparities: issues, controversies and solutions.
AB  - Colorectal cancer (CRC) is the second leading cause of cancer related deaths in
      the United States. There are significant differences in CRC incidence and
      mortality by race with the highest burden occurring among blacks. The underlying
      factors contributing to CRC disparities are multiple and complex. Studies have
      suggested that a higher prevalence of putative risk factors for CRC, limited
      access to healthcare services, lower utilization of healthcare resources and
      increased biological susceptibilities contribute to this disparity by race. This
      article reviews the factors associated with the disproportionally higher burden
      of CRC among blacks; addresses the controversies regarding the age to begin CRC
      screening and the screening modality to use for blacks; and proffers solutions to
      eliminate CRC disparity by race. 

PMID- 24574762
TI  - Evolving treatment strategies for colorectal cancer: a critical review of current
      therapeutic options.
AB  - Management of rectal cancer has markedly evolved over the last two decades. New
      technologies of staging have allowed a more precise definition of tumor
      extension. Refinements in surgical concepts and techniques have resulted in
      higher rates of sphincter preservation and better functional outcome for patients
      with this malignancy. Although, preoperative chemoradiotherapy followed by total
      mesorectal excision has become the standard of care for locally advanced tumors,
      many controversial matters in management of rectal cancer still need to be
      defined. These include the feasibility of a non-surgical approach after a
      favorable response to neoadjuvant therapy, the ideal margins of surgical
      resection for sphincter preservation and the adequacy of minimally invasive
      techniques of tumor resection. In this article, after an extensive search in
      PubMed and Embase databases, we critically review the current strategies and the
      most debatable matters in treatment of rectal cancer. 

PMID- 24574763
TI  - Colorectal cancer biomarkers: to be or not to be? Cautionary tales from a road
      well travelled.
AB  - Colorectal cancer (CRC) is the second most common cause of cancer-related death
      worldwide and places a major economic burden on the global health care system.
      The time frame for development from premalignant to malignant disease typically
      spans 10-15 years, and this latent period provides an ideal opportunity for early
      detection and intervention to improve patient outcomes. Currently, early
      diagnosis of CRC is hampered by a lack of suitable non-invasive biomarkers that
      are clinically or economically acceptable for population-based screening. New
      blood-based protein biomarkers for early detection of CRC are therefore urgently
      required. The success of clinical biomarker discovery and validation studies is
      critically dependent on understanding and adjusting for potential experimental,
      analytical, and biological factors that can interfere with the robust
      interpretation of results. In this review we outline some important
      considerations for research groups undertaking biomarker research with exemplars
      from our studies. Implementation of experimental strategies to minimise the
      potential effects of these problems will facilitate the identification of panels
      of biomarkers with the sensitivity and specificity required for the development
      of successful tests for the early detection and surveillance of CRC. 

PMID- 24574764
TI  - How to select the optimal treatment for first line metastatic colorectal cancer.
AB  - Choice of first line treatment for patients with metastatic colorectal cancer
      (mCRC) is based on tumour and patient related factors and molecular information
      for determination of individual treatment aim and thus treatment intensity.
      Recent advances (e.g., extended RAS testing) enable tailored patient assignment
      to the most beneficial treatment approach. Besides fluoropyrimidines, irinotecan
      and oxaliplatin, a broad variety of molecular targeting agents are currently
      available, e.g., anti-angiogenic agents (bevacizumab) and epidermal growth factor
      receptor (EGFR) antibodies (cetuximab, panitumumab) for first line treatment of
      mCRC. Although some combinations should be avoided (e.g., oral or bolus
      fluoropyrimidines, oxaliplatin and EGFR antibodies), treatment options range from
      single agent to highly effective four-drug regimen. Preliminary data comparing
      EGFR antibodies and bevacizumab, both with chemotherapy, seem to favour EGFR
      antibodies in RAS wildtype disease. However, choosing the most appropriate
      treatment approach for mCRC patients remains a complex issue, with numerous open
      questions. 

PMID- 24574766
TI  - Cancer stem cells in colorectal cancer from pathogenesis to therapy:
      controversies and perspectives.
AB  - Colorectal cancer remains one of the most common and lethal malignancies
      worldwide despite the use of various therapeutic strategies. A better
      understanding of the mechanisms responsible for tumor initiation and progression
      is essential for the development of novel, more powerful therapies. The
      traditional, so-called "stochastic model" of tumor development, which assumes
      that each cancer cell is tumorigenic, has been deeply challenged during the past
      decade by the identification of cancer stem cells (CSCs), a biologically distinct
      subset of cells within the bulk of tumor mass. This discovery led to the
      development of the hierarchical model of tumorigenesis which assumes that only
      CSCs have the ability to initiate tumor growth, both at primary and metastatic
      sites. This model implies that the elimination of all CSCs is fundamental to
      eradicate tumors and that failure to do so might be responsible for the
      occurrence of relapses and/or metastases frequently observed in the clinical
      management of colorectal cancer patients. Identification and isolation of CSCs is
      essential for a better understanding of their role in the tumorigenetic process
      and for the development of CSC-specific therapies. Several methods have been used
      for this purpose and many efforts have been focused on the identification of
      specific CSC-surface markers. This review provides an overview of the proposed
      roles of CSC in human colorectal tumorigenesis focusing on the most important
      molecules identified as CSC-specific markers in colorectal cancer and on the
      potential strategies for the development of CSC-targeted therapy. 

PMID- 24574765
TI  - Inflammation and colorectal cancer, when microbiota-host mutualism breaks.
AB  - Structural changes in the gut microbial community have been shown to accompany
      the progressive development of colorectal cancer. In this review we discuss
      recent hypotheses on the mechanisms involved in the bacteria-mediated
      carcinogenesis, as well as the triggering factors favoring the shift of the gut
      microbiota from a mutualistic to a pro-carcinogenic configuration. The possible
      role of inflammation, bacterial toxins and toxic microbiota metabolites in
      colorectal cancer onset is specifically discussed. On the other hand, the
      strategic role of inflammation as the keystone factor in driving microbiota to
      become carcinogenic is suggested. As a common outcome of different environmental
      and endogenous triggers, such as diet, aging, pathogen infection or genetic
      predisposition, inflammation can compromise the microbiota-host mutualism,
      forcing the increase of pathobionts at the expense of health-promoting groups,
      and allowing the microbiota to acquire an overall pro-inflammatory configuration.
      Consolidating inflammation in the gut, and favoring the bloom of toxigenic
      bacterial drivers, these changes in the gut microbial ecosystem have been
      suggested as pivotal in promoting carcinogenesis. In this context, it will become
      of primary importance to implement dietary or probiotics-based interventions
      aimed at preserving the microbiota-host mutualism along aging, counteracting
      deviations that favor a pro-carcinogenic microbiota asset. 

PMID- 24574767
TI  - Genetic and epigenetic biomarkers for diagnosis, prognosis and treatment of
      colorectal cancer.
AB  - Colorectal cancer (CRC) is one of the most common cancer worldwide and results
      from the accumulation of mutations and epimutations in colonic mucosa cells
      ultimately leading to cell proliferation and metastasis. Unfortunately, CRC
      prognosis is still poor and the search of novel diagnostic and prognostic
      biomarkers is highly desired to prevent CRC-related deaths. The present article
      aims to summarize the most recent findings concerning the use of either genetic
      or epigenetic (mainly related to DNA methylation) biomarkers for CRC diagnosis,
      prognosis, and response to treatment. Recent large-scale DNA methylation studies
      suggest that CRC can be divided into several subtypes according to the frequency
      of DNA methylation and those of mutations in key CRC genes, and that this is
      reflected by different prognostic outcomes. Increasing evidence suggests that the
      analysis of DNA methylation in blood or fecal specimens could represent a
      valuable non-invasive diagnostic tool for CRC. Moreover, a broad spectrum of
      studies indicates that the inter-individual response to chemotherapeutic
      treatments depends on both epigenetic modifications and genetic mutations
      occurring in colorectal cancer cells, thereby opening the way for a personalized
      medicine. Overall, combining genetic and epigenetic data might represent the most
      promising tool for a proper diagnostic, prognostic and therapeutic approach. 

PMID- 24574768
TI  - Circulating and stool nucleic acid analysis for colorectal cancer diagnosis.
AB  - In recent years, the need to identify molecular markers characterized by high
      sensitivity and specificity in detecting and monitoring early and colorectal
      cancer lesions has increased. Up to now, none of the markers or panels of markers
      analyzed have met the rigorous standards required of a screening program. The
      important discovery of circulating nucleic acids in biological fluids has aroused
      intense scientific interest because of their usefulness in malignant and non
      malignant diseases. Over time, their yield and stability have been identified and
      compared with other "standard" biomarkers. The analysis of circulating DNA from
      blood and stool is a relatively simple and non-invasive procedure, representing a
      very attractive marker to detect genetic and epigenetic mutations and to monitor
      disease progression. A correlation between blood and stool biomarkers could also
      help to enhance currently available diagnostic approaches. However, various
      processing and analytic problems need to be resolved before such an approach can
      be applied in clinical practice. 

PMID- 24574769
TI  - Cysteinyl leukotrienes and their receptors: bridging inflammation and colorectal
      cancer.
AB  - Long-standing inflammation has emerged as a hallmark of neoplastic transformation
      of epithelial cells and may be a limiting factor of successful conventional tumor
      therapies. A complex milieu composed of distinct stromal and immune cells,
      soluble factors and inflammatory mediators plays a crucial role in supporting and
      promoting various types of cancers. An augmented inflammatory response can
      predispose a patient to colorectal cancer (CRC). Common risk factors associated
      with CRC development include diet and lifestyle, altered intestinal microbiota
      and commensals, and chronic inflammatory bowel diseases. Cysteinyl leukotrienes
      are potent inflammatory metabolites synthesized from arachidonic acid and have a
      broad range of functions involved in the etiology of various pathologies. This
      review discusses the important role of cysteinyl leukotriene signaling in linking
      inflammation and CRC. 

PMID- 24574771
TI  - Radiofrequency ablation as treatment for pulmonary metastasis of colorectal
      cancer.
AB  - Radiofrequency ablation (RFA) causes focal coagulation necrosis in tissue. Its
      first clinical application was reported in 2000, and RFA has since been commonly
      used in both primary and metastatic lung cancer. The procedure is typically
      performed using computed tomography guidance, and the techniques for introducing
      the electrode to the tumor are simple and resemble those used in percutaneous
      lung biopsy. The most common complication is pneumothorax, which occurs in up to
      50% of procedures; chest tube placement for pneumothorax is required in up to 25%
      of procedures. Other severe complications, such as pleural effusion requiring
      chest tube placement, infection, and nerve injury, are rare. The local efficacy
      depends on tumor size, and local progression after RFA is not rare, occurring in
      10% or more of patients. The local progression rate is particularly high for
      tumors > 3 cm. Repeat RFA may be used to treat local progression. Short- to mid
      term survival after RFA appears promising and is approximately 85%-95% at 1 year
      and 45%-55% at 3 years. Long-term survival data are sparse. Better survival may
      be expected for patients with small metastasis, low carcinoembryonic antigen
      levels, and/or no extrapulmonary metastasis. The notable advantages of RFA are
      that it is simple and minimally invasive; preserves pulmonary function; can be
      repeated; and is applicable regardless of previous treatments. Its most
      substantial limitation is limited local efficacy. Although surgery is still the
      method of choice for treatment with curative intent, the ultimate application of
      RFA may be to replace metastasectomy for small metastases. Randomized trials
      comparing RFA with surgery are needed. 

PMID- 24574770
TI  - Accumulation of aberrant DNA methylation during colorectal cancer development.
AB  - Despite the recent advances in the therapeutic modalities, colorectal cancer
      (CRC) remains to be one of the most common causes of cancer-related death. CRC
      arises through accumulation of multiple genetic and epigenetic alterations that
      transform normal colonic epithelium into adenocarcinomas. Among crucial roles of
      epigenetic alterations, gene silencing by aberrant DNA methylation of promoter
      regions is one of the most important epigenetic mechanisms. Recent comprehensive
      methylation analyses on genome-wide scale revealed that sporadic CRC can be
      classified into distinct epigenotypes. Each epigenotype cooperates with specific
      genetic alterations, suggesting that they represent different molecular
      carcinogenic pathways. Precursor lesions of CRC, such as conventional and
      serrated adenomas, already show similar methylation accumulation to CRC, and can
      therefore be classified into those epigenotypes of CRC. In addition, specific DNA
      methylation already occurs in the normal colonic mucosa, which might be utilized
      for prediction of the personal CRC risk. DNA methylation is suggested to occur at
      an earlier stage than carcinoma formation, and may predict the molecular basis
      for future development of CRC. Here, we review DNA methylation and CRC
      classification, and discuss the possible clinical usefulness of DNA methylation
      as biomarkers for the diagnosis, prediction of the prognosis and the response to
      therapy of CRC. 

PMID- 24574772
TI  - Overview of single-port laparoscopic surgery for colorectal cancers: past,
      present, and the future.
AB  - Single-port laparoscopic surgery (SPLS) is implemented through a tailored minimal
      single incision through which a number of laparoscopic instruments access.
      Introduction of operation-customized port system, utilization of a camera without
      a separate external light, and instruments with different lengths has brought the
      favorable environment for SPLS. However, performing SPLS still creates several
      hardships compared to multiport laparoscopic surgery; a single-port system
      inevitably leads to clashing of surgical instruments due to crowding. To overcome
      such difficulties, investigators has developed novel concepts and maneuvers,
      including the concept of inverse triangulation and the maneuvers of pivoting,
      spreading out dissection, hanging suture, and transluminal traction. The final
      destination of SPLS is expected to be a completely seamless operation, maximizing
      the minimal invasiveness. Specimen extraction through the umbilicus can undermine
      cosmesis by inducing a larger incision. Therefore, hybrid laparoscopic technique,
      which combined laparoscopic surgical technique with natural orifice specimen
      extraction (NOSE)--i.e., transvaginal or transanal route-, has been developed.
      SPLS and NOSE seemed to be the best combination in pursuit of minimal
      invasiveness. In the near future, robotic SPLS with natural orifice transluminal
      endoscopic surgery's way of specimen extraction seems to be pursued. It is
      expected to provide a completely or nearly complete seamless operation regardless
      of location of the lesion in the abdomen.

PMID- 24574774
TI  - Portal inflow preservation during portal diversion in small-for-size syndrome.
AB  - AIM: To investigate the impact of portal inflow on liver remnants in a stable pig
      model of small-for-size syndrome. METHODS: Twenty pigs underwent mesocaval shunt
      (MCS) surgery followed by 85%-90% hepatectomy. The control group had no shunt
      placement; the S1 group had portal flow maintained at an average of 2.0 times the
      baseline values; and the S2 group had portal flow maintained at an average of 3.2
      times the baseline flow. The effect of portal functional competition on the liver
      remnant was investigated for 48 h postoperatively. Data were presented as mean +/
      SD. Statistical significance was determined using Student's t test (SPSS,
      Chicago, IL, United States). Values of P < 0.05 were considered statistically
      significant. RESULTS: At 24 h after hepatectomy, biochemical and histological
      changes were not significantly different between the S1 and S2 groups, but
      changes in both sets of variables were significantly less than in the control
      group. At 48 h, biochemical and histological changes were significantly less in
      the S2 group than in the S1 or control group. The regeneration index was
      significantly higher in the S2 group than in the S1 group, and was similar to
      that in the control group. Apoptosis index, serum lipopolysaccharide, and
      bacterial DNA levels were significantly lower in the S2 group than in the other
      two groups. CONCLUSION: Diversion of portal inflow using MCS reduces portal
      overflow injury. Excessive diversion of portal inflow inhibits liver regeneration
      following major hepatectomy. Maintaining portal inflow at an average of 3.2 times
      above baseline helps promote hypertrophy of the liver remnant and reduce
      apoptosis.

PMID- 24574775
TI  - Novel esophageal squamous cell carcinoma bone metastatic clone isolated by
      scintigraphy, X ray and micro PET/CT.
AB  - AIM: To establish a Chinese esophageal squamous cell carcinoma (ESCC) cell line
      with high bone metastasis potency using (99m)Tc-methylene diphosphonate ((99m)Tc
      MDP) micro-pinhole scintigraphy, X ray and micro-positron emission
      tomography/computed tomography (PET/CT) for exploring the mechanism of occurrence
      and development in esophageal cancer. METHODS: The cells came from a BALB/c nu/nu
      immunodeficient mouse, and oncogenic tumor tissue was from a surgical specimen
      from a 61-year-old male patient with ESCC. The cell growth curve was mapped and
      analysis of chromosome karyotype was performed. Approximately 1 * 106 oncogenic
      cells were injected into the left cardiac ventricle of immunodeficient mice. The
      bone metastatic lesions of tumor-bearing mice were detected by (99m)Tc-MDP
      scintigraphy, micro-PET/CT and X-ray, and were resected from the mice under deep
      anesthesia. The bone metastatic cells in the lesions were used for culture and
      for repeated intracardiac inoculation. This in vivo/in vitro experimental
      metastasis study was repeated for four cycles. All of the suspicious bone sites
      were confirmed by pathology. Real-time polymerase chain reaction was used to
      compare the gene expression in the parental cells and in the bone metastatic
      clone. RESULTS: The surgical specimen was implanted subcutaneously in
      immunodeficient mice and the tumorigenesis rate was 100%. First-passage oncogenic
      cells were named CEK-Sq-1. The chromosome karyotype analysis of the cell line was
      hypotriploid. The bone metastasis rate went from 20% with the first-passage
      oncogenic cells via intracardiac inoculation to 90% after four cycles. The
      established bone metastasis clone named CEK-Sq-1BM had a high potential to
      metastasize in bone, including mandible, humerus, thoracic and lumbar vertebrae,
      scapula and femur. The bone metastasis lesions were successfully detected by
      micro-pinhole bone scintigraphy, micro-PET/CT, and X-ray. The sensitivity,
      specificity and accuracy of the micro-pinhole scintigraphy, X-ray, and micro
      PET/CT imaging examinations were: 89.66%/32%/80%, 88.2%/100%/89.2%, and
      88.75%/77.5%/87.5%, respectively. Some gene expression difference was found
      between parental and bone metastasis cells. CONCLUSION: This newly established
      Chinese ESCC cell line and animal model may provide a useful tool for the study
      of the pathogenesis and development of esophageal carcinoma.

PMID- 24574773
TI  - Neuroanatomy of lower gastrointestinal pain disorders.
AB  - Chronic abdominal pain accompanying intestinal inflammation emerges from the
      hyperresponsiveness of neuronal, immune and endocrine signaling pathways within
      the intestines, the peripheral and the central nervous system. In this article we
      review how the sensory nerve information from the healthy and the hypersensitive
      bowel is encoded and conveyed to the brain. The gut milieu is continuously
      monitored by intrinsic enteric afferents, and an extrinsic nervous network
      comprising vagal, pelvic and splanchnic afferents. The extrinsic afferents convey
      gut stimuli to second order neurons within the superficial spinal cord layers.
      These neurons cross the white commissure and ascend in the anterolateral quadrant
      and in the ipsilateral dorsal column of the dorsal horn to higher brain centers,
      mostly subserving regulatory functions. Within the supraspinal regions and the
      brainstem, pathways descend to modulate the sensory input. Because of this
      multiple level control, only a small proportion of gut signals actually reaches
      the level of consciousness to induce sensation or pain. In inflammatory bowel
      disease (IBD) and irritable bowel syndrome (IBS) patients, however, long-term
      neuroplastic changes have occurred in the brain-gut axis which results in chronic
      abdominal pain. This sensitization may be driven on the one hand by peripheral
      mechanisms within the intestinal wall which encompasses an interplay between
      immunocytes, enterochromaffin cells, resident macrophages, neurons and smooth
      muscles. On the other hand, neuronal synaptic changes along with increased
      neurotransmitter release in the spinal cord and brain leads to a state of central
      wind-up. Also life factors such as but not limited to inflammation and stress
      contribute to hypersensitivity. All together, the degree to which each of these
      mechanisms contribute to hypersensitivity in IBD and IBS might be disease- and
      even patient-dependent. Mapping of sensitization throughout animal and human
      studies may significantly improve our understanding of sensitization in IBD and
      IBS. On the long run, this knowledge can be put forward in potential therapeutic
      targets for abdominal pain in these conditions. 

PMID- 24574778
TI  - Intra-gastric triacetin alters upper gastrointestinal motility in conscious dogs.
AB  - AIM: To examine the effect of intra-gastric triacetin on both upper
      gastrointestinal motility and proximal gastric tone in conscious dogs. METHODS:
      Three beagle dogs under sedation were surgically implanted with gastrocutaneous
      fistula in the gastric body and force transducers in the gastric antrum and
      duodenum. Beginning at week-2 after insertion, the animals were either fasted for
      24 h or fed a liquid meal 2-3 h before the experiment. With the animals fully
      conscious, a polyethylene bag was inserted into the proximal stomach through the
      gastrocutaneous fistula, followed by 15 min of air inflation (minimal distending
      pressure of +2 mmHg) and then 20 mL of a low-, mid- or high-concentration
      triacetin solution (0.5%, 1.0% and 2.0%) or warm water (vehicle control). The
      proximal stomach receptive volume and gastric antral and duodenal contractions
      were measured over 10 min. The experiment was repeated twice per week over
      several months, with each animal receiving at least one infusion of the various
      triacetin solutions and the vehicle at different times. Intergroup differences
      were assessed by ANOVA and Bonferroni-Dunn post-hoc testing. RESULTS: Intra
      gastric infusion of mid- and high-concentration triacetin induced an increase in
      the proximal stomach receptive volume, and the average increase induced by the
      high-concentration at 0-4 min after infusion was significantly greater than that
      induced by the vehicle control (62.4 +/- 9.8 vs 18.4 +/- 4.7, P < 0.01). The mid-
      and high-concentration triacetin also produced a temporary inhibition of the
      gastric antral contractions at 2 min after infusions; however, only the fasted
      group showed triacetin-induced antral contractile inhibition that was
      significantly greater than that in the vehicle control group (P < 0.05). In
      addition, only the fasted group showed a high-concentration triacetin-induced
      increase in duodenal contractions at 9-10 min that was significantly different
      from that in the vehicle control group (P < 0.05). CONCLUSION: Intra-gastric
      infusion of 1.0%-2.0% triacetin delays gastric emptying by increasing proximal
      stomach receptive volume, temporarily inhibiting gastric antral contractions and
      facilitating duodenal contractions.

PMID- 24574777
TI  - Biopsy-driven diagnosis in infants with cholestatic jaundice in Iran.
AB  - AIM: To determine the frequencies of diagnoses confirmed by liver biopsy in
      infants with cholestasis in an Iranian pediatric hospital. METHODS: This was a
      retrospective study conducted in a tertiary referral children's hospital in Iran.
      We retrieved all pathology reports of liver biopsies from children less than two
      years of age who had presented for evaluation of cholestatic jaundice from March
      2001 to March 2011. Additional specimen samples obtained from archived pathology
      blocks were reviewed by a pathologist blinded to the final diagnosis. These
      results were compared with the pathology reports from chart records to ensure
      consensus and eliminate any inconsistencies in final diagnoses. A structured
      checklist was used to gather information on multiple variables including age,
      sex, gestational age at birth, birth weight, age at which hyperbilirubinemia
      manifested, presence and identification of associated anomalies, clinical
      manifestations, and histological findings from liver biopsies. The baseline data
      are reported using descriptive statistics, and differences between groups were
      assessed by Fisher's exact test and Student's t test when indicated. RESULTS:
      Fifty-five cases (28 females; 27 males) of infantile cholestasis (IC) were
      included in this study. The mean serum total bilirubin and direct bilirubin at
      presentation were 13.6 +/- 5.9 and 7.3 +/- 3.4, respectively. Forty cases (72.7%)
      were the product of term pregnancies. Common associated clinical findings were
      acholic stool in 33 cases (60.0%), hepatomegaly in 30 cases (54.5%), and dark
      colored urine in 21 cases (38.2%). Biliary atresia (BA) was the most frequent
      diagnosis, found in 32 cases (58.2%), followed by intrahepatic bile duct paucity
      found in 6 cases (10.9%), metabolic disease in 6 cases (10.9%), idiopathic
      neonatal hepatitis in 5 cases (9.1%), choledochal cyst in 2 cases (3.6%), liver
      cirrhosis in 2 cases (3.6%), and progressive familial intrahepatic cholestasis
      and portal fibrosis each in 1 case (1.8%). The mean times for jaundice onset and
      liver biopsy were 43.8 and 102.0 d, respectively. In BA, the mean age at jaundice
      presentation was 21 d and for liver biopsy was 87.5 d, representing a mean delay
      of 66.5 d. CONCLUSION: A significant delay was found between IC presentation and
      liver biopsy, which is detrimental in conditions that can cause irreversible
      liver damage, such as BA.

PMID- 24574776
TI  - Fecal immunochemical test accuracy in average-risk colorectal cancer screening.
AB  - AIM: To assess the fecal immunochemical test (FIT) accuracy for colorectal cancer
      (CRC) and advanced neoplasia (AN) detection in CRC screening. METHODS: We
      performed a multicentric, prospective, double blind study of diagnostic tests on
      asymptomatic average-risk individuals submitted to screening colonoscopy. Two
      stool samples were collected and the fecal hemoglobin concentration was
      determined in the first sample (FIT1) and the highest level of both samples
      (FITmax) using the OC-sensorTM. Areas under the curve (AUC) for CRC and AN were
      calculated. The best FIT1 and FITmax cut-off values for CRC were determined. At
      this threshold, number needed to scope (NNS) to detect a CRC and an AN and the
      cost per lesion detected were calculated. RESULTS: About 779 individuals were
      included. An AN was found in 97 (12.5%) individuals: a CRC in 5 (0.6%) and an
      advanced adenoma (>= 10 mm, villous histology or high grade dysplasia) in 92
      (11.9%) subjects. For CRC diagnosis, FIT1 AUC was 0.96 (95%CI: 0.95-0.98) and
      FITmax AUC was 0.95 (95%CI: 0.93-0.97). For AN, FIT1 and FITmax AUC were similar
      (0.72, 95%CI: 0.66-0.78 vs 0.73, 95%CI: 0.68-0.79, respectively, P = 0.34).
      Depending on the number of determinations and the positivity threshold cut-off
      used sensitivity for AN detection ranged between 28% and 42% and specificity
      between 91% and 97%. At the best cut-off point for CRC detection (115 ng/mL), the
      NNS to detect a CRC were 10.2 and 15.8; and the cost per CRC was 1814? and 2985?
      on FIT1 and FITmax strategies respectively. At this threshold the sensitivity,
      NNS and cost per AN detected were 30%, 1.76, and 306?, in FIT1 strategy, and 36%,
      2.26? and 426?, in FITmax strategy, respectively. CONCLUSION: Performing two
      tests does not improve diagnostic accuracy, but increases cost and NNS to detect
      a lesion.

PMID- 24574779
TI  - Long-term pretreatment with proton pump inhibitor and Helicobacter pylori
      eradication rates.
AB  - AIM: To investigate whether proton pump inhibitor (PPI) pretreatment influences
      Helicobacter pylori eradication rate. METHODS: We retrospectively reviewed H.
      pylori-infected patients who were treated with a standard triple regimen (PPI,
      amoxicillin 1 g, and clarithromycin 500 mg, all twice daily for 7 d). The
      diagnosis of H. pylori infection and its eradication was assessed with the rapid
      urease test, histological examination by silver staining, or the 13C-urea breath
      test. We divided the patients into two groups: one received the standard
      eradication regimen without PPI pretreatment (Group A), and the other received
      PPI pretreatment (Group B). The patients in Group B were reclassified into three
      groups based on the duration of PPI pretreatment: Group B-I (3-14 d), Group B-II
      (15-55 d), and Group B-III (>= 56 d). RESULTS: A total of 1090 patients were
      analyzed and the overall eradication rate was 80.9%. The cure rate in Group B
      (81.2%, 420/517) was not significantly different from that in Group A (79.2%,
      454/573). The eradication rates in Group B-I, B-II and B-III were 80.1%
      (117/146), 81.8% (224/274) and 81.4% (79/97), respectively. CONCLUSION: PPI
      pretreatment did not affect H. pylori eradication rate, regardless of the
      medication period.

PMID- 24574780
TI  - Phase I study of postoperative radiotherapy combined with capecitabine for
      gastric cancer.
AB  - AIM: To determine the maximum tolerated dose (MTD) and dose-limiting toxicity
      (DLT) of capecitabine combined with postoperative radiotherapy for gastric
      cancer. METHODS: We enrolled patients with any T stage and node-positive
      gastroesophageal or gastric adenocarcinoma after complete resection with negative
      margins (R0) or microscopic (R1) or macroscopic (R2) resection. Intensity
      modulated radiotherapy (IMRT) using a five-to-seven-field, coplanar, sliding
      window technique was delivered to the tumor bed (T4b), anastomosis site, duodenal
      stump and regional lymph nodes (LNs) to a total dose of 45 Gy (1.8 Gy/fraction, 5
      d/wk). Patients with R1 or R2 resection received 10.8 Gy as a boost. Capecitabine
      was administered twice daily on every radiotherapy treatment day in a dose
      escalation schedule (mg/m2) of 625 (level I, n = 6), 700 (level II, n = 6), 800
      (level III, n = 6), 900 (level IV, n = 0) and 1000 (level V, n = 0). DLT was
      defined as grade 4 leukopenia or neutropenia, grade 3-4 thrombocytopenia or
      anemia and grade 3-4 non-hematological toxicity. RESULTS: Between October 2007
      and August 2009, 18 patients (12 men, 6 women; median age, 54 years) were
      enrolled in the study. The median number of positive LNs was 6, and total number
      of resected LNs was 19. Twelve patients underwent R0 resection (66.7%). Fifteen
      patients received adjuvant chemotherapy under the leucovorin, fluorouracil and
      oxaliplatin (FOLFOX4) regimen. Six patients each were enrolled at dose levels I,
      II and III. Grade 1-3 leukopenia (16 patients, 88.9%), anorexia (15, 83.3%) and
      nausea (15, 83.3%) were the most common toxicities. Grade 3 anorexia/nausea and
      grade 4 vomiting occurred in one level-I patient. Grade 3 anorexia and nausea
      occurred in one level-II patient. One level-III patient developed grade 4
      neutropenia, while another developed grade 3 radiation esophagitis. No abnormal
      liver or renal function examinations were observed. Three patients did not finish
      chemoradiotherapy because of DLTs and two without DLTs received sequential boosts
      (total dose, 55.8 Gy). CONCLUSION: The MTD of capecitabine was 800 mg/m2 twice
      daily concurrent with IMRT for gastric cancer after surgery. The DLTs were
      anorexia/nausea, vomiting, neutropenia and radiation esophagitis.

PMID- 24574781
TI  - Expression of granulocyte colony-stimulating factor receptor in rectal cancer.
AB  - AIM: To evaluate whether granulocyte colony-stimulating factor receptor (G-CSFR)
      expression before preoperative irradiation can predict the radiosensitivity of
      rectal cancer. METHODS: The expression of G-CSFR was examined, using
      immunohistochemistry, in biopsy specimens from 126 patients with locally advanced
      rectal adenocarcinoma before preoperative irradiation. Radiosensitivity was then
      evaluated according to the Rectal Cancer Regression Grading. Endoscopic
      inspection was used to detect the tumor area in each patient. General patient
      information, such as age, gender, lymph node status, tumor size and degree of
      differentiation was recorded. A statistical analysis was then performed to
      evaluate the correlation between clinical or pathological parameters and G-CSFR
      expression in tumors. RESULTS: According to endoscopic inspection, the tumor area
      ranged from 4 to 48 cm2 (median, 15 cm2). Positive G-CSFR immunoreactions (G
      CSFR+) were observed in 85 specimens, and negative (G-CSFR-) in 41. No
      significant differences were found in age, gender, tumor invasion, lymph node
      status and tumor size between G-CSFR+ and G-CSFR- patients. G-CSFR expression was
      positively correlated with poor radiotherapy response (58.8% vs 75.6%, P = 0.014,
      r = 0.219). The proportion of well-differentiated tumors in G-CSFR+ and G-CSFR-
      patients was 24.7% and 36.6%, respectively. Sphincter preservation was observed
      in 57.6% of G-CSFR+ patients and 78.5% of G-CSFR- patients. Significant
      correlations were found between G-CSFR expression and tumor differentiation
      (24.7% vs 36.6%, P = 0.019, r = 0.210), as well as sphincter preservation (57.6%
      vs 78.5%, P = 0.044, r = 0.180). CONCLUSION: The expression of G-CSFR before
      preoperative irradiation may predict the radiosensitivity of rectal cancer.

PMID- 24574782
TI  - Role of hydrogen sulfide in portal hypertension and esophagogastric junction
      vascular disease.
AB  - AIM: To investigate the association between endogenous hydrogen sulfide (H2S) and
      portal hypertension as well as its effect on vascular smooth muscle cells.
      METHODS: Portal hypertension patients were categorized by Child-Pugh score based
      on bilirubin and albumin levels, prothrombin time, ascites and hepatic
      encephalopathy. Plasma H2S concentrations and portal vein diameters (PVDs) were
      compared between portal hypertension patients and control participants, as well
      as between portal hypertension patients with varying degrees of severity. In
      addition, we established a rabbit hepatic schistosomiasis portal hypertension
      (SPH) model and analyzed liver morphology, fibrosis grade, plasma and liver
      tissue H2S concentrations, as well as cystathionine gamma-lyase (CSE) activity
      and phosphorylated extracellular signal-regulated kinase (pERK)1/2, B cell
      lymphoma (Bcl)-2 and Bcl-XL expression in portal vein smooth muscle cells, in
      addition to their H2S-induced apoptosis rates. RESULTS: In portal hypertension
      patients, endogenous H2S levels were significantly lower than those in healthy
      controls. The more severe the disease was, the lower were the H2S plasma levels,
      which were inversely correlated with PVD and Child-Pugh score. Liver tissue H2S
      concentrations and CSE expression were significantly lower in the SPH rabbit
      livers compared with the control animals, starting at 3 wk, whereas pERK 1/2
      expressions gradually increased 12-20 wk after SPH model establishment. In portal
      vein smooth muscle cells, increasing H2S levels led to increased apoptosis, while
      Bcl-2 and Bcl-XL expression decreased. CONCLUSION: H2S prevents vascular
      restructuring caused by excessive proliferation of smooth muscle cells via
      apoptosis induction, which helps to maintain normal vascular structures.

PMID- 24574783
TI  - Diagnostic value of contrast enhanced ultrasound for splenic artery complications
      following acute pancreatitis.
AB  - AIM: To assess the value of contrast-enhanced ultrasound (CEUS) in diagnosing
      splenic artery complications (SACs) after acute pancreatitis (AP). METHODS: One
      hundred and eighteen patients with AP were enrolled in the study. All patients
      were examined by CEUS and contrast-enhanced computed tomography (CECT). CECT was
      accepted as a gold standard for the diagnosis of SACs in AP. The diagnostic
      accuracy of splenic CEUS and pancreatic CEUS was compared with that of CECT.
      Splenic infarction was the diagnostic criterion for splenic artery embolism and
      local dysperfusion of the splenic parenchyma was the diagnostic criterion for
      splenic arterial stenosis. The incidence of splenic sub-capsular hemorrhage,
      splenic artery aneurysms, and splenic rupture was all lower than that of SACs.
      RESULTS: Nine patients were diagnosed as having SACs after AP by CECT among the
      118 patients. The patients with SACs were diagnosed with severe acute
      pancreatitis (SAP). Among them, 6 lesions were diagnosed as splenic artery
      embolism, 5 as splenic artery aneurysms, and 1 as splenic arterial stenosis. No
      lesion was diagnosed by pancreatic CEUS and 5 lesions were diagnosed by splenic
      CEUS. By splenic CEUS, 4 cases were diagnosed as splenic artery embolism and 1 as
      splenic arterial stenosis. The accuracy of splenic CEUS in diagnosis of SACs in
      SAP was 41.7% (5/12), which was higher than that of pancreatic CEUS (0%).
      CONCLUSION: Splenic CEUS is a supplementary method for pancreatic CEUS in AP
      patients, which can decrease missed diagnosis of SACs.

PMID- 24574784
TI  - Combination of chemotherapy and immunotherapy for colon cancer in China: a meta
      analysis.
AB  - AIM: To investigate whether autologous dendritic cell (DC)-cytokine-induced
      killer (CIK) cell therapy is able to improve the therapeutic efficacy of
      chemotherapy in colon cancer. METHODS: We conducted a systematic review of
      published papers from the sources of MEDLINE, the Cochrane Central Register of
      Controlled Trials, EMBASE, the Wanfang Database, the China Science and Technology
      Periodical Database and China Journal Net. Published data were extracted
      independently by two authors using predefined database templates. The quality of
      the data from individual papers was also assessed. The effects of chemotherapy
      were compared with those of chemotherapy in combination with DC-CIK
      immunotherapy. The pooled analysis was performed using the data from random or
      fixed-effect models. RESULTS: Seven trials matched our inclusion criteria (n =
      533). The overall analysis showed significant survival benefit [one-year overall
      survival (OS), P < 0.0001; two-year OS, P = 0.009; three-year OS, P = 0.002] in
      favor of DC-CIK immunotherapy combined with chemotherapy. Disease-free survival
      (DFS) rate was improved after the combination of DC-CIK immunotherapy and
      chemotherapy (one-year DFS, P < 0.0001; two-year DFS, P = 0.002; three-year DFS,
      P = 0.02). An improved overall response rate (P = 0.009) was also observed in
      patients who received DC-CIK therapy. Furthermore, the analysis of T-lymphocyte
      subsets in peripheral blood indicated that the number of CD4+ T cells
      significantly increased in the DC-CIK plus chemotherapy group (P < 0.05).
      CONCLUSION: The combination of DC-CIK immunotherapy and chemotherapy was superior
      in prolonging the survival time and enhancing immunological responses.

PMID- 24574785
TI  - Meta-analysis of immunohistochemical expression of hypoxia inducible factor
      1alpha as a prognostic role in gastric cancer.
AB  - AIM: To conduct a meta-analysis to evaluate the prognostic role of hypoxia
      inducible factor-1alpha (HIF-1alpha) expression in gastric cancer. METHODS: The
      PubMed, EMBASE, and Web of Science databases were searched systematically for all
      articles published in English before August, 2013. Pooled effect was calculated
      from the available data to evaluate the association between HIF-1alpha expression
      and 5-year overall survival and tumor clinicopathological features in gastric
      cancer patients. Pooled odds ratios (ORs) with 95%CIs were calculated using
      either a fixed-effects or a random-effects model. RESULTS: Nine studies matched
      the selection criteria, which reported on 1103 subjects, 548 of whom had HIF
      1alpha positive expression (50%). This meta-analysis indicated that HIF-1alpha
      positive expression in gastric cancer correlated with lower 5-year overall
      survival (OR = 0.36; 95%CI: 0.21-0.64), worse tumor differentiation (OR = 0.38;
      95%CI: 0.23-0.64), deeper invasion (OR = 0.42; 95%CI: 0.32-0.57), higher rates of
      lymph node metastasis (OR = 2.23; 95%CI: 1.46-3.40), lymphatic invasion (OR =
      2.50; 95%CI: 1.46-4.28), and vascular invasion (OR = 1.80; 95%CI: 1.29-2.51), and
      higher TNM stage (III + IV) (OR = 0.31; 95%CI: 0.15-0.60). CONCLUSION: HIF-1alpha
      positive expression indicates a poor prognosis for patients with gastric cancer.
      Further studies are required to confirm these results.

PMID- 24574786
TI  - Family case of achalasia cardia: case report and review of literature.
AB  - Achalasia cardia is an idiopathic disease that occurs as a result of inflammation
      and degeneration of myenteric plexi leading to the loss of postganglionic
      inhibitory neurons required for relaxation of the lower esophageal sphincter and
      peristalsis of the esophagus. The main symptoms of achalasia are dysphagia,
      regurgitation, chest pain and weight loss. At present, there are three main
      hypotheses regarding etiology of achalasia cardia which are under consideration,
      these are genetic, infectious and autoimmune. Genetic theory is one of the most
      widely discussed. Case report given below represents an inheritable case of
      achalasia cardia which was not diagnosed for a long time in an 81-year-old woman
      and her 58-year-old daughter. 

PMID- 24574787
TI  - Endoscopic transgastric drainage of a gastric wall abscess after endoscopic
      submucosal dissection.
AB  - A 63-year-old woman was referred to our hospital for further examination because
      of an incidental finding of early gastric cancer. Endoscopic submucosal
      dissection (ESD) was successfully performed for complete resection of the tumor.
      On the first post-ESD day, the patient suddenly complained of abdominal pain
      after an episode of vomiting. Abdominal computed tomography (CT) showed delayed
      perforation after ESD. The patient was conservatively treated with an intravenous
      proton pump inhibitor and antibiotics. On the fifth post-ESD day, CT revealed a
      gastric wall abscess in the gastric body. Gastroscopy revealed a gastric fistula
      at the edge of the post-ESD ulcer, and pus was found flowing into the stomach. An
      intradrainage stent and an extradrainage nasocystic catheter were successfully
      inserted into the abscess for endoscopic transgastric drainage. After the
      procedure, the clinical symptoms and laboratory test results improved quickly.
      Two months later, a follow-up CT scan showed no collection of pus. Consequently,
      the intradrainage stent was removed. Although the gastric wall abscess recurred 2
      wk after stent removal, it recovered soon after endoscopic transgastric drainage.
      Finally, after stent removal and oral antibiotic treatment for 1 mo, no
      recurrence of the gastric wall abscess was found. 

PMID- 24574788
TI  - Laparoscopic partial cystectomy with mucosal stripping of extraluminal duodenal
      duplication cysts.
AB  - Duodenal duplication cysts are rare congenital anomalies. Duodenal duplication
      should be considered in the differential diagnosis of patients who present with
      abdominal symptoms with cystic structures neighboring the duodenum. Here, we
      present an 8-year-old girl with a duodenal duplication cyst treated with partial
      cystectomy with mucosal stripping performed laparoscopically. Laparoscopic
      surgery can be considered as a treatment option for duodenal duplication cysts,
      especially in extraluminal locations. 

PMID- 24574790
TI  - When combination therapy isn't working: emerging therapies for the management of
      inflammatory bowel disease.
AB  - Although antagonists of tumor necrosis factor have resulted in major therapeutic
      benefits in inflammatory bowel disease, the magnitude and durability of response
      are variable. Similar to previously available drugs such as 5-aminosalicylates
      and immunomodulators, the therapeutic effect is not universal leaving many people
      searching for options. The development of newer agents has benefited from
      advances in the understanding of the pathophysiology of the disease. Uncontrolled
      activation of the acquired immune system has an important role, and lymphocytes,
      cytokines, and adhesion molecules are broadly targeted for therapeutic
      intervention. There is increasing evidence of an important role of the innate
      immune system and the intestinal epithelium, and the therapeutic paradigm is also
      shifting from immunosuppression to the reinforcement of the intestinal barrier,
      and modification of the disease process. In this review, we explore the
      limitation of current therapy as well as mechanisms of actions of new drugs and
      the efficacy and adverse events from data from clinical trials. 

PMID- 24574789
TI  - Novel methylxanthine derivative-mediated anti-inflammatory effects in
      inflammatory bowel disease.
AB  - Family 18 chitinases have a binding capacity with chitin, a polymer of N
      acetylglucosamine. Recent studies strongly suggested that chitinase 3-like 1
      (CHI3L1, also known as YKL-40) and acidic mammalian chitinase, the two major
      members of family 18 chitinases, play a pivotal role in the pathogenesis of
      inflammatory bowel disease (IBD), bronchial asthma and several other inflammatory
      disorders. Based on the data from high-throughput screening, it has been found
      that three methylxanthine derivatives, caffeine, theophylline, and
      pentoxifylline, have competitive inhibitory effects against a fungal family 18
      chitinase by specifically interacting with conserved tryptophans in the active
      site of this protein. Methylxanthine derivatives are also known as adenosine
      receptor antagonists, phosphodiesterase inhibitors and histone deacetylase
      inducers. Anti-inflammatory effects of methylxanthine derivatives have been well
      documented in the literature. For example, a beneficial link between coffee or
      caffeine consumption and type 2 diabetes as well as liver cirrhosis has been
      reported. Furthermore, theophylline has a long history of being used as a
      bronchodilator in asthma therapy, and pentoxifylline has an immuno-modulating
      effect for peripheral vascular disease. However, it is still largely unknown
      whether these methylxanthine derivative-mediated anti-inflammatory effects are
      associated with the inhibition of CHI3L1-induced cytoplasmic signaling cascades
      in epithelial cells. In this review article we will examine the above possibility
      and summarize the biological significance of methylxanthine derivatives in
      intestinal epithelial cells. We hope that this study will provide a rationale for
      the development of methylxanthine derivatives, in particular caffeine, -based
      anti-inflammatory therapeutics in the field of IBD and IBD-associated
      carcinogenesis.

PMID- 24574791
TI  - Prevention of post-operative recurrence of Crohn's disease.
AB  - Endoscopic and clinical recurrence of Crohn's disease (CD) is a common occurrence
      after surgical resection. Smokers, those with perforating disease, and those with
      myenteric plexitis are all at higher risk of recurrence. A number of medical
      therapies have been shown to reduce this risk in clinical trials. Metronidazole,
      thiopurines and anti-tumour necrosis factors (TNFs) are all effective in reducing
      the risk of endoscopic or clinical recurrence of CD. Since these are preventative
      agents, the benefits of prophylaxis need to be weighed-against the risk of
      adverse events from, and costs of, therapy. Patients who are high risk for post
      operative recurrence should be considered for early medical prophylaxis with an
      anti-TNF. Patients who have few to no risk factors are likely best served by a
      three-month course of antibiotics followed by tailored therapy based on endoscopy
      at one year. Clinical recurrence rates are variable, and methods to stratify
      patients into high and low risk populations combined with prophylaxis tailored to
      endoscopic recurrence would be an effective strategy in treating these patients. 

PMID- 24574792
TI  - Role of capsule endoscopy in inflammatory bowel disease.
AB  - Videocapsule endoscopy (VCE) has revolutionized our ability to visualize the
      small bowel mucosa. This modality is a valuable tool for the diagnosis of obscure
      small bowel Crohn's disease (CD), and can also be used for monitoring of disease
      activity in patients with established small-bowel CD, detection of complications
      such as obscure bleeding and neoplasms, evaluation of response to anti
      inflammatory treatment and postoperative recurrence following small bowel
      resection. VCE could also be an important tool in the management of patients with
      unclassified inflammatory bowel disease, potentially resulting in
      reclassification of these patients as having CD. Reports on postoperative
      monitoring and evaluation of patients with ileal pouch-anal anastomosis who have
      developed pouchitis have recenty been published. Monitoring of colonic
      inflammatory activity in patients with ulcerative colitis using the recently
      developed colonic capsule has also been reported. Capsule endoscopy is associated
      with an excellent safety profile. Although retention risk is increased in
      patients with small bowel CD, this risk can be significanty decreased by a
      routine utilization of a dissolvable patency capsule preceding the ingestion of
      the diagnostic capsule. This paper contains an overview of the current and future
      clinical applications of capsule endoscopy in inflammatory bowel disease.

PMID- 24574794
TI  - Magnetic resonance imaging in children and adolescents with chronic inflammatory
      bowel disease.
AB  - Inflammatory bowel diseases (IBD) represent challenges, both from a diagnostic,
      and therapeutic point of view. Deep-seated anatomic structures are difficult to
      assess by ultrasound technique alone. As radiation-free alternative cross
      sectional imaging method, magnetic resonance imaging of the intestinal structures
      is costly and time-consuming. Examination of pediatric patients imply additional
      considerations: reduction of body motions in younger children and consideration
      of the most appropriate preparation, and examination technique. The demanding
      Sellink technique is the only means for appropriately distending the lesser
      intestine in order to detect small bowel strictures. Oral intake of contrast
      medium (CM) alone shows its limitations regarding distensibility. The need for
      intravenous contrast media application needs to be considered, too. Active
      inflammation of both intestinal wall, and mesentery can be demonstrated
      accurately. Nevertheless, viable alternatives to CM application is desirable,
      considering non-negligible adverse reactions. Recent data suggest diffusion
      weighted imaging might fill this diagnostic gap. Irrespective of sequence
      technique chosen, bowel movement remains a major obstacle. Antispasmolytics in
      their function as smooth muscle relaxants help in improving image quality,
      however, their use in children might be off-label. Optimal preparation for the
      examination and appropriate imaging technique allow for diagnosing typical
      patterns of changes in IBD, such as bowel wall thickening, ulcers, mural
      stratification, strictures, creeping fat, and comb sign, and lymphadenopathy. The
      article gives a detailed overview of current significance of magnetic resonance
      imaging pediatric patients suffering from IBD, considering indications,
      limitations, and safety aspects. 

PMID- 24574793
TI  - Intestinal barrier in inflammatory bowel disease.
AB  - A complex mucosal barrier protects as the first line of defense the surface of
      the healthy intestinal tract from adhesion and invasion by luminal
      microorganisms. In this review, we provide an overview about the major components
      of this protective system as for example an intact epithelium, the synthesis of
      various antimicrobial peptides (AMPs) and the formation of the mucus layer. We
      highlight the crucial importance of their correct functioning for the maintenance
      of a proper intestinal function and the prevention of dysbiosis and disease.
      Barrier disturbances including a defective production of AMPs, alterations in
      thickness or composition of the intestinal mucus layer, alterations of pattern
      recognition receptors, defects in the process of autophagy as well as unresolved
      endoplasmic reticulum stress result in an inadequate host protection and are
      thought to play a crucial role in the pathogenesis of the inflammatory bowel
      diseases Crohn's disease and ulcerative colitis. 

PMID- 24574797
TI  - Inflammatory bowel disease: an increased risk factor for neurologic
      complications.
AB  - Only a very few systematic studies have investigated the frequency of neurologic
      disorders in patients with Crohn's disease (CD) and ulcerative colitis (UC),
      which are the two main types of inflammatory bowel disease (IBD). Results have
      been inconsistent and variable, owing to differences in case-finding methods and
      evaluated outcomes in different studies. The most frequent neurologic
      manifestations reported in CD and UC populations are cerebrovascular disease
      (with either arterial or venous events), demyelinating central nervous system
      disease, and peripheral neuropathy (whether axonal or demyelinating); however,
      the literature describes numerous nervous system disorders as being associated
      with IBD. The pathogenesis of nervous system tissue involvement in IBD has yet to
      be elucidated, although it seems to be related to immune mechanisms or
      prothrombotic states. The recently-introduced tumor necrosis factor (TNF)
      inhibitors have proven successful in controlling moderate to severe IBD activity.
      However, severe neurologic disorders associated with TNF inhibitors have been
      reported, which therefore raises concerns regarding the effect of anti-TNF-alpha
      antibodies on the nervous system. Although neurological involvement associated
      with IBD is rarely reported, gastroenterologists should be aware of the
      neurologic manifestations of IBD in order to provide early treatment, which is
      crucial for preventing major neurologic morbidity. 

PMID- 24574798
TI  - Epidemiological studies of migration and environmental risk factors in the
      inflammatory bowel diseases.
AB  - Inflammatory bowel diseases (IBD) are idiopathic chronic diseases of the
      gastrointestinal tract well known to be associated with both genetic and
      environmental risk factors. Permissive genotypes may manifest into clinical
      phenotypes under certain environmental influences and these may be best studied
      from migratory studies. Exploring differences between first and second generation
      migrants may further highlight the contribution of environmental factors towards
      the development of IBD. There are few opportunities that have been offered so
      far. We aim to review the available migration studies on IBD, evaluate the known
      environmental factors associated with IBD, and explore modern migration patterns
      to identify new opportunities and candidate migrant groups in IBD migration
      research. 

PMID- 24574795
TI  - Role of the gut microbiota in inflammatory bowel disease pathogenesis: what have
      we learnt in the past 10 years?
AB  - Our understanding of the microbial involvement in inflammatory bowel disease
      (IBD) pathogenesis has increased exponentially over the past decade. The
      development of newer molecular tools for the global assessment of the gut
      microbiome and the identification of nucleotide-binding oligomerization domain
      containing protein 2 in 2001 and other susceptibility genes for Crohn's disease
      in particular has led to better understanding of the aetiopathogenesis of IBD.
      The microbial studies have elaborated the normal composition of the gut
      microbiome and its perturbations in the setting of IBD. This altered microbiome
      or "dysbiosis" is a key player in the protracted course of inflammation in IBD.
      Numerous genome-wide association studies have identified further genes involved
      in gastrointestinal innate immunity (including polymorphisms in genes involved in
      autophagy: ATG16L1 and IGRM), which have helped elucidate the relationship of the
      local innate immunity with the adjacent luminal bacteria. These developments have
      also spurred the search for specific pathogens which may have a role in the
      metamorphosis of the gut microbiome from a symbiotic entity to a putative
      pathogenic one. Here we review advances in our understanding of microbial
      involvement in IBD pathogenesis over the past 10 years and offer insight into how
      this will shape our therapeutic management of the disease in the coming years.

PMID- 24574796
TI  - Therapy with stem cells in inflammatory bowel disease.
AB  - Inflammatory bowel disease (IBD) affects a part of the young population and has a
      strong impact upon quality of life. The underlying etiology is not known, and the
      existing treatments are not curative. Furthermore, a significant percentage of
      patients are refractory to therapy. In recent years there have been great
      advances in our knowledge of stem cells and their therapeutic applications. In
      this context, autologous hematopoietic stem cell transplantation (HSCT) has been
      used in application to severe refractory Crohn's disease (CD), with encouraging
      results. Allogenic HSCT would correct the genetic defects of the immune system,
      but is currently not accepted for the treatment of IBD because of its
      considerable risks. Mesenchymal stem cells (MSCs) have immune regulatory and
      regenerative properties, and low immunogenicity (both autologous and allogenic
      MSCs). Based on these properties, MSCs have been used via the systemic route in
      IBD with promising results, though it is still too soon to draw firm conclusions.
      Their local administration in perianal CD is the field where most progress has
      been made in recent years, with encouraging results. The next few years will be
      decisive for defining the role of such therapy in the management of IBD.

PMID- 24574799
TI  - What is left when anti-tumour necrosis factor therapy in inflammatory bowel
      diseases fails?
AB  - The inflammatory bowel diseases (IBDs) are chronic incurable conditions that
      primarily present in young patients. Being incurable, the IBDs may be part of the
      patient's life for many years and these conditions require therapies that will be
      effective over the long-term. Surgery in Crohn's disease does not cure the
      disease with endoscopic recurrent in up to 70% of patients 1 year post resection.
      This means that, the patient will require many years of medications and the goal
      of the treating physician is to induce and maintain long-term remission without
      side effects. The development of the anti-tumour necrosis factor alpha (TNFalpha)
      agents has been a magnificent clinical advance in IBD, but they are not always
      effective, with loss of response overtime and, at times, discontinuation is
      required secondary to side effects. So what options are available if of the anti
      TNFalpha agents can no longer be used? This review aims to provide other options
      for the physician, to remind them of the older established medications like
      azathioprine/6-mercaptopurine and methotrexate, the less established medications
      like mycophenolate mofetil and tacrolimus as well as newer therapeutic options
      like the anti-integins, which block the trafficking of leukocytes into the
      intestinal mucosa. The location of the intestinal inflammation must also be
      considered, as topical therapeutic agents may also be worthwhile to consider in
      the long-term management of the more challenging IBD patient. The more options
      that are available the more likely the patient will be able to have tailored
      therapy to treat their disease and a better long-term outcome.

PMID- 24574800
TI  - Campylobacter concisus and inflammatory bowel disease.
AB  - Investigation of the possible role of Campylobacter concisus (C. concisus) in
      inflammatory bowel disease (IBD) is an emerging research area. Despite the
      association found between C. concisus and IBD, it has been difficult to explain
      how C. concisus, a bacterium that is commonly present in the human oral cavity,
      may contribute to the development of enteric diseases. The evidence presented in
      this review shows that some C. concisus strains in the oral cavity acquired
      zonula occludens toxin (zot) gene from a virus (prophage) and that C. concisus
      Zot shares conserved motifs with both Vibrio cholerae Zot receptor binding domain
      and human zonulin receptor binding domain. Both Vibrio cholerae Zot and human
      zonulin are known to increase intestinal permeability by affecting the tight
      junctions. Increased intestinal permeability is a feature of IBD. Based on these
      data, we propose that a primary barrier function defect caused by C. concisus Zot
      is a mechanism by which zot-positive C. concisus strains may trigger the onset
      and relapse of IBD.

PMID- 24574802
TI  - Factors correlating with acoustic radiation force impulse elastography in chronic
      hepatitis C.
AB  - AIM: To investigate the factors other than fibrosis stage correlating with
      acoustic radiation force impulse (ARFI) elastograpy in chronic hepatitis C.
      METHODS: ARFI elastograpy was performed in 108 consecutive patients with chronic
      hepatitis C who underwent a liver biopsy. The proportion of fibrosis area in the
      biopsy specimens was measured by computer-assisted morphometric image analysis.
      RESULTS: ARFI correlated significantly with fibrosis stage (beta = 0.1865, P <
      0.0001) and hyaluronic acid levels (beta = 0.0008, P = 0.0039) in all patients by
      multiple regression analysis. Fibrosis area correlated significantly with ARFI by
      Spearman's rank correlation test but not by multiple regression analysis. ARFI
      correlated significantly with body mass index (BMI) (beta = -0.0334, P = 0.0001)
      in F 0 or F 1, with gamma-glutamyltranspeptidase levels (beta = 0.0048, P =
      0.0012) in F 2, and with fibrosis stage (beta = 0.2921, P = 0.0044) and
      hyaluronic acid levels (beta = 0.0012, P = 0.0025) in F 3 or F 4. The ARFI cutoff
      value was 1.28 m/s for F >= 2, 1.44 m/s for F >= 3, and 1.73 m/s for F 4.
      CONCLUSION: ARFI correlated with fibrosis stage and hyaluronic acid but not with
      inflammation. ARFI was affected by BMI, gamma-glutamyltranspeptidase, and
      hyaluronic acid in each fibrosis stage.

PMID- 24574804
TI  - Bax protein may influence the invasion of colorectal cancer.
AB  - AIM: To evaluate the expression of Bcl-xL, Bak, and Bax proteins in correlation
      with particular clinico-histopathological parameters, including tumor invasion
      front, in patients with colorectal cancer. METHODS: The expression of these
      proteins was evaluated with the use of the immunohistochemical method in 50
      primary tumors. RESULTS: According to observations, a low expression of Bax and
      Bak proteins is related to the localization of the tumor in the rectum (P < 0.05
      and P < 0.05 respectively), which may explain an increased incidence of
      colorectal cancer in this area. A positive expression of Bax protein also
      correlates with the presence of cancer cell infiltration to lymph and blood
      vessels (P < 0.05), which may suggest the participation of this protein in the
      early stages of colorectal cancer progression. Moreover, a positive expression of
      Bcl-xL protein correlated with a positive expression of Bak protein. This may
      suggest a greater participation of Bcl-xL protein in the inhibition of the
      proapoptotic Bak protein, but not the Bax protein. CONCLUSION: Bax protein is
      probably very significant in the cancerogenesis mechanism in the large intestine.

PMID- 24574801
TI  - Novel hepatocellular carcinoma molecules with prognostic and therapeutic
      potentials.
AB  - Hepatocellular carcinoma (HCC), the predominant form of primary liver cancer, is
      the sixth most common cancer worldwide and the third leading cause of cancer
      related death. The difficulty to diagnose early cancer stages, the aggressive
      behaviors of HCC, and the poor effectiveness of therapeutic treatments, represent
      the reasons for the quite similar deaths per year and incidence number.
      Considering the fact that the diagnosis of HCC typically occurs in the advanced
      stages of the disease when the therapeutic options have only modest efficacy, the
      possibility to identify early diagnostic markers could be of significant benefit.
      So far, a large number of biomarkers have been associated to HCC progression and
      aggressiveness, but many of them turned out not to be of practical utility. This
      is the reason why active investigations are ongoing in this field. Given the huge
      amount of published works aimed at the identification of HCC biomarkers, in this
      review we mainly focused on the data published in the last year, with particular
      attention to the role of (1) molecular and biochemical cellular markers; (2)
      micro-interfering RNAs; (3) epigenetic variations; and (4) tumor stroma. It is
      worth mentioning that a significant number of the HCC markers described in the
      present review may be utilized also as targets for novel therapeutic approaches,
      indicating the tight relation between diagnosis and therapy. In conclusion, we
      believe that integrated researches among the different lines of investigation
      indicated above should represent the winning strategies to identify effective HCC
      markers and therapeutic targets. 

PMID- 24574803
TI  - Antinociceptive effects of novel melatonin receptor agonists in mouse models of
      abdominal pain.
AB  - AIM: To characterize the antinociceptive action of the novel melatonin receptor
      (MT) agonists, Neu-P11 and Neu-P12 in animal models of visceral pain. METHODS:
      Visceral pain was induced by intracolonic (ic) application of mustard oil or
      capsaicin solution or by intraperitoneal (ip) administration of acetic acid. Neu
      P11, Neu-P12, or melatonin were given ip or orally and their effects on pain
      induced behavioral responses were evaluated. To identify the receptors involved,
      the non-selective MT1/MT2 receptor antagonist luzindole, the MT2 receptor
      antagonist 4-P-PDOT, or the MU-opioid receptor antagonist naloxone were injected
      ip or intracerebroventricularly (icv) prior to the induction of pain. RESULTS:
      Orally and ip administered melatonin, Neu-P11, and Neu-P12 reduced pain responses
      in a dose-dependent manner. Neu-P12 was more effective and displayed longer
      duration of action compared to melatonin. The antinociceptive effects of Neu-P11
      or Neu-P12 were antagonized by ip or icv. administered naloxone.
      Intracerebroventricularly, but not ip administration of luzindole or 4-P-PDOT
      blocked the antinociceptive actions of Neu-P11 or Neu-P12. CONCLUSION: Neu-P12
      produced the most potent and long-lasting antinociceptive effect. Further
      development of Neu-P12 for future treatment of abdominal pain seems promising.

PMID- 24574805
TI  - Reduced hemoglobin and increased C-reactive protein are associated with upper
      gastrointestinal bleeding.
AB  - AIM: To investigate the early upper gastrointestinal endoscopy (endoscopy)
      significantly reduces mortality resulting from upper gastrointestinal (GI)
      bleeding. METHODS: Upper GI bleeding was defined as 1a, 1b, 2a, and 2b according
      to the Forrest classification. The hemoglobin (Hb), and C-reactive protein (CRP)
      were examined at around the day of endoscopy and 3 mo prior to endoscopy. The
      rate of change was calculated as follows: (the result of blood examination on the
      day of endoscopy - the results of blood examination 3 mo prior to
      endoscopy)/(results of blood examination 3 mo prior to endoscopy). Receiver
      operating characteristic curves were created to determine threshold values.
      RESULTS: Seventy-nine men and 77 women were enrolled. There were 17 patients with
      upper GI bleeding: 12 with a gastric ulcer, 3 with a duodenal ulcer, 1 with an
      acute gastric mucosal lesion, and 1 with gastric cancer. The area under the curve
      (AUC), threshold, sensitivity, and specificity of Hb around the day of endoscopy
      were 0.902, 11.7 g/dL, 94.1%, and 77.1%, respectively, while those of CRP were
      0.722, 0.5 mg/dL, 70.5%, and 73%, respectively. The AUC, threshold, sensitivity,
      and specificity of the rate of change of Hb were 0.851, -21.3%, 76.4%, and 82.6%,
      respectively, while those of CRP were 0.901, 100%, 100%, and 82.5%, respectively.
      CONCLUSION: Predictors for upper GI bleeding were Hb < 11.7 g/dL, reduction rate
      in the Hb > 21.3% and an increase in the CRP > 100%, 3 mo before endoscopy.

PMID- 24574806
TI  - Risk factors for proximal migration of biliary tube stents.
AB  - AIM: To analyze the risk factors for biliary stent migration in patients with
      benign and malignant strictures. METHODS: Endoscopic stent placement was
      performed in 396 patients with bile duct stenosis, at our institution, between
      June 2003 and March 2009. The indications for bile duct stent implantation
      included common bile duct stone in 190 patients, malignant lesions in 112,
      chronic pancreatitis in 62, autoimmune pancreatitis in 14, trauma in eight,
      surgical complications in six, and primary sclerosing cholangitis (PSC) in four.
      We retrospectively examined the frequency of stent migration, and analyzed the
      patient factors (disease, whether endoscopic sphincterotomy was performed,
      location of bile duct stenosis and diameter of the bile duct) and stent
      characteristics (duration of stent placement, stent type, diameter and length).
      Moreover, we investigated retrieval methods for migrated stents and their
      associated success rates. RESULTS: The frequency of tube stent migration in the
      total patient population was 3.5%. The cases in which tube stent migration
      occurred included those with common bile duct stones (3/190; 1.6%), malignant
      lesions (2/112; 1.8%), chronic pancreatitis (4/62; 6.5%), autoimmune pancreatitis
      (2/14; 14.3%), trauma (1/8; 12.5%), surgical complications (2/6; 33.3%), and PSC
      (0/4; 0%). The potential risk factors for migration included bile duct stenosis
      secondary to benign disease such as chronic pancreatitis and autoimmune
      pancreatitis (P = 0.030); stenosis of the lower bile duct (P = 0.031); bile duct
      diameter > 10 mm (P = 0.023); duration of stent placement > 1 mo (P = 0.007); use
      of straight-type stents (P < 0.001); and 10-Fr sized stents (P < 0.001).
      Retrieval of the migrated stents was successful in all cases. The grasping
      technique, using a basket or snare, was effective for pig-tailed or thin and
      straight stents, whereas the guidewire cannulation technique was effective for
      thick and straight stents. CONCLUSION: Migration of tube stents within the bile
      duct is rare but possible, and it is important to determine the risk factors
      involved in stent migration.

PMID- 24574807
TI  - A new hemostatic clip for endoscopic surgery that can maintain blood flow after
      clipping.
AB  - AIM: To develop a new hemostatic device for endoscopic surgery that can control
      the bleeding without completely occluding the bleeding vessel. METHODS: A
      hemostatic clip and its applier that can stanch bleeding while maintaining blood
      flow through the clipped vessel was introduced, and the performance of the
      proposed clip was evaluated using in vitro and in vivo experiments. RESULTS:
      During in vitro experiments, no leakage was found after clipping at cuts made in
      artificial vessels, and flow was maintained through the clipped artificial
      vessels. In experiments on rats, all the implanted clips occluded the target
      vessels successfully, and no bleeding or tissue damage was observed at the
      operative site after the rats were euthanized on postoperative day 7. In
      experiments on pigs, bleeding stopped immediately after partial clipping of a
      damaged vessel, and some amount of blood flow was consistently maintained through
      the clipped vessel after hemostasis. CONCLUSION: We believe that the proposed
      hemostatic clip and clip applier can enhance patient safety during laparoscopic
      surgery.

PMID- 24574808
TI  - Evaluation of specific fecal protein biochips for the diagnosis of colorectal
      cancer.
AB  - AIM: To develop and initially test a potential fecal protein biochip for the
      screening of colorectal cancer (CRC). METHODS: Fecal protein from 20 colorectal
      cancer patients and 20 healthy controls were extracted from all of the fecal
      samples and screened for proteomic differences using a Biotin label-based protein
      array. Candidate proteins were then verified by ELISA. Finally, we will select
      out the significant protein and a seven-target multiplex fecal protein biochip
      was generated and tested for 20 fecal samples to determine the effectiveness of
      the biochip on identifying CRC. And the value of the protein biochip would be
      discussed. RESULTS: After tested by protein biochip of the fecal protein from 20
      colorectal cancer patients and 20 healthy controls and levels of calprotectin, M2
      pyruvatekinase, angiopoietin-2, fibroblast growth factor-23 (FGF-23), proteins of
      the matrix metalloproteinase, thrombopoietin (TPO) and interleukin-13 (IL-13)
      were significantly different between CRC and healthy controls. The sensitivity of
      all the seven proteins combined was 0.7, specificity was 0.4, and area under the
      receiver operating characteristics was 0.729. The most promising combinations of
      test proteins were FGF-23, TPO, and IL-13, reaching a sensitivity of 0.7 and a
      specificity of 0.7. The combination of FGF-23 and TPO scored highest with
      sensitivity of 0.7 and specificity of 0.8. Its mean that the combination of FGF
      23 and TPO has the highest value for the diagnosis of CRC in our study.
      CONCLUSION: A protein biochip composed of proteins found to be elevated in the
      feces of colorectal cancer patients has great potential as a noninvasive
      diagnostic for colorectal cancer. The addition of new protein biomarkers and
      technologies, as they are discovered, is an excellent avenue of future research.

PMID- 24574809
TI  - Endoscopic ultrasonography for staging of T1a and T1b esophageal squamous cell
      carcinoma.
AB  - AIM: To investigate the accuracy of Endoscopic ultrasound (EUS) in staging and
      sub-staging T1a and T1b esophageal squamous cell carcinoma (ESCC). METHODS: A
      retrospective analysis involving 72 patients with pathologically confirmed T1a or
      T1b ESCC, was undertaken between January 2005 and December 2011 in Sun Yat-sen
      University Cancer Center. The accuracy and efficiency of EUS for detecting stages
      T1a and T1b ESCC were examined. RESULTS: The overall accuracy of EUS for
      detecting stage T1a or T1b ESCC was 70.8% (51/72), and the sensitivity was 74.3%.
      77.8% (7/9) of lesions originated in the upper thoracic region, 73.1% (38/52) in
      the mid-thoracic region and 72.7% (8/11) in the lower thoracic region.
      Multivariate analysis revealed that the diagnostic accuracy of EUS was closely
      related to lesion length (F = 4.984, P = 0.029). CONCLUSION: EUS demonstrated
      median degree of accuracy for distinguishing between stages T1a and T1b ESCC.
      Therefore, it is necessary to improve EUS for staging early ESCC.

PMID- 24574811
TI  - A trichobezoar in a child with undiagnosed celiac disease: a case report.
AB  - Celiac disease is a chronic, immune-mediated enteropathy caused by a permanent
      sensitivity to ingested gluten cereals that develops in genetically susceptible
      individuals. The classic presentation of celiac disease includes symptoms of
      malabsorption but has long been associated with cognitive, emotional, and
      behavioral disorders. We describe an 8-year-old patient with non-scarring
      alopecia and diagnosed with trichotillomania. Furthermore, she presented with a 3
      year history of poor appetite and two or three annual episodes of mushy, fatty
      stools. Laboratory investigations showed a normal hemoglobin concentration and a
      low ferritin level. Serologic studies showed an elevated tissue immunoglobulin G
      anti-tissue transglutaminase level. A duodenal biopsy showed subtotal villous
      atrophy and crypt hyperplasia, and a large gastric trichobezoar was found in the
      stomach. Immediately after beginning a gluten-free diet, complete relief of
      trichotillomania and trichophagia was achieved. In this report, we describe a
      behavioral disorder as a primary phenomenon of celiac disease, irrespective of
      nutritional status. 

PMID- 24574810
TI  - Oleanolic acid and ursolic acid inhibit proliferation in transformed rat hepatic
      oval cells.
AB  - AIM: To investigate H2O2-induced promotion proliferation and malignant
      transformation in WB-F344 cells and anti-tumor effects of ursolic acid (UA) and
      oleanolic acid (OA). METHODS: WB-F344 cells were continuously exposed to 7 x 10(
      7) mol/L H2O2 for 21 d. Observations of cell morphology, colony formation rates,
      flow cytometric analysis of cell cycle changes and aneuploidy formation indicated
      that H2O2 was able to induce malignant transformation of WB-F344 cells. We
      treated malignantly transformed WB-F344 cells with 4 MUmol/L OA or 8 MUmol/L UA
      for 72 h and analyzed the cell cycle distribution by flow cytometry. RESULTS: MTT
      assay showed that 7 x 10(-7) mol/L H2O2 decreased G1 phase subpopulation from
      73.8% to 49.6% compared with the control group, and increased S phase
      subpopulation from 14.5% to 31.8% (P < 0.05 vs control group). Cell morphology
      showed that nucleus to cytoplasm ratio increased, many mitotic cells, prokaryotes
      and even tumor giant cells were shown in H2O2-induced WB-F344 cells. Fluorescence
      activated cell sorting analysis showed that WB-F344 cell aneuploidy increased to
      12% following H2O2 treatment. Flow cytometric analysis of the transformed WB-F344
      cells following treatment with OA (4 MUmol/L) and UA (8 MUmol/L) showed that OA
      increased G1 subpopulation to 68.6%, compared to 49.7% in unexposed cells. UA
      increased G1 subpopulation to 67.4% compared to 49.7% in unexposed cells (P <
      0.05 vs H2O2 model group). CONCLUSION: H2O2 causes the malignant transformation
      of WB-F344 cells. OA and UA exert anti-tumor effects by inhibiting the
      proliferation in malignantly transformed WB-F344 cells.

PMID- 24574812
TI  - Nodular fasciitis in the mesentery, a differential diagnosis of peritoneal
      carcinomatosis.
AB  - Nodular fasciitis is a benign proliferative lesion composed of fibroblast-like
      cells that affects various sites in the body. We describe a patient with nodular
      fasciitis in the mesentery, encountered during laparotomy for the treatment of
      ascending colon cancer. The nodular fasciitis in our patient resembled peritoneal
      dissemination of malignancy on macroscopic observation. Because the treatment
      options change with concomitant peritoneal dissemination of gastrointestinal
      tract malignancy, recognition of this rare condition and preparation for
      unexpected nodular lesions are crucial. 

PMID- 24574813
TI  - Epstein-Barr virus-associated lymphoepithelioma-like early gastric carcinomas and
      endoscopic submucosal dissection: case series.
AB  - Epstein-Barr virus (EBV)-associated lymphoepithelioma-like gastric carcinoma
      (LELC) is characterized by a lower lymph node (LN) metastasis rate and a higher
      survival rate than other forms of gastric cancer. Although current prognosis for
      LELC is favorable, the most common approach is radical gastrectomy involving an
      extensive D2 lymph node dissection. Here, we report four cases of EBV-associated
      early LELC that were treated by an alternative approach, endoscopic submucosal
      dissection (ESD). The long-term outcome of this procedure is discussed. All
      patients were treated by ESD en bloc, and all ESD specimens showed tumor-free
      lateral resection margins. None of the lesions showed lymphovascular invasion. A
      pathological examination of ESD specimens revealed submucosal invasion of more
      than 500 MUm in all four cases. One patient underwent additional radical surgery
      post-ESD; no residual tumor or LN metastasis was noted in the surgical specimen.
      The other three patients did not undergo additional surgery, either because of
      severe comorbidity or their refusal to undergo operation, but were subjected to
      medical follow-up. None of the ESD-treated patients reported local recurrence or
      distant metastases during the 27-32 mo of follow-up after ESD.

PMID- 24574815
TI  - Pericyst: the outermost layer of hydatid cyst.
AB  - Hydatid disease, caused by the parasite Echinococcus granulosus, mostly affects
      the liver and the lungs with hydatid cysts which consist of three layers: (1) the
      outer pericyst; (2) the middle laminated membrane; and (3) the inner germinal
      layer. Pericyst, as the outermost layer of the hydatid cyst, is made by host
      cells encasing the hydatid cyst. An extremely close interaction exists between
      this host tissue and the parasite, and any degenerative changes of the pericyst
      would result in hydatid cyst degeneration or rupture. The pericyst plays an
      undeniably important role in the development and survival of the hydatid cyst. 

PMID- 24574814
TI  - Bowel mesentery (meso-appendix) microcystic/reticular schwannoma: case report and
      literature review.
AB  - Microcystic/reticular schwannoma is a recently described variant of schwannoma
      with a predilection for the gastrointestinal tract. Due to overlapping features
      with other tumors, unawareness of this tumor type may lead to diagnostic and
      therapeutic pitfalls. We here report a case of microcystic/reticular schwannoma
      arising in the meso-appendix of a 43-year-old woman. The tumor was incidentally
      discovered by computed tomography scan for unrelated reasons. A laparoscopic
      operation was performed shortly after admission. Histological examination
      revealed a circumscribed tumor with a striking microcystic and cribriform
      architecture. Immunohistochemically, the tumor cells were diffusely positive for
      S100 protein, glial fibrillary acid protein and protein gene product 9.5, which
      were consistent with a peripheral nerve sheath tumor. The patient remains well
      with no signs of recurrence at a 10-mo follow-up. To our knowledge, this is the
      first case of microcystic/reticular schwannoma arising in the meso-appendix.
      Albeit very rare, microcystic/reticular schwannoma should be included in the
      differential diagnosis of appendiceal tumors. 

PMID- 24574816
TI  - It's the Dose, Not the Hypothesis: Reply to.

PMID- 24574817
TI  - Mental health and risk of secondary medical complications in adults with
      pediatric-onset spinal cord injury.
AB  - OBJECTIVE: To investigate mental health problems in adults with pediatric-onset
      spinal cord injury (SCI) and explore how these problems relate to the risk of
      negative outcomes over time. METHOD: The study included 466 adults who sustained
      an SCI prior to age 19 years and had been injured for at least 1 year.
      Participants were interviewed on an approximately annual basis using a study
      specific questionnaire and standardized measures of depression, anxiety,
      substance use, and community involvement. Generalized estimating equations were
      used to assess the risk of negative outcomes across time as a function of
      depression, anxiety, and substance misuse. RESULTS: Of the participants who
      reported on each domain of mental health, 26% reported misuse of alcohol or drugs
      (122/466), 21% reported problems with depression (78/360), and 29% reported
      problems with anxiety (49/168). Depression was associated with increased odds of
      pressure ulcers, urinary tract infections, hospitalizations, pain, and smoking
      and lower levels of economic independence and mobility. Anxiety was associated
      with increased odds of hospitalization, pain, and smoking. Substance misuse
      predicted an increased risk of pressure ulcers, pain, and smoking and decreased
      odds of occupational involvement. When examining the effect of mental health with
      time, results showed that depression accelerated the risk of urinary tract
      infections, respiratory complications, and hospitalizations and anxiety and
      depression accelerated risk for lower occupational independence. CONCLUSIONS: The
      added burden that mental health difficulties pose for medical and psychosocial
      outcomes highlight the importance of monitoring and treating mental health
      symptoms in pediatric-onset SCI.

PMID- 24574818
TI  - Depression and anxiety in adolescents with pediatric-onset spinal cord injury.
AB  - BACKGROUND: Little is known about depression and anxiety in adolescents with
      spinal cord injury (SCI). OBJECTIVE: To examine how depression, anxiety, suicidal
      ideation, and usage of treatment differ by age and sex among adolescents with
      SCI. METHOD: Youth 12 to 18 years old who had acquired SCI at least 1 year prior
      were recruited from 3 specialty hospitals. They completed the Children's
      Depression Inventory (ages 12-17 years) or Beck Depression Inventory-II (18
      years), and Revised Children's Manifest Anxiety Scale (12-18 years). Analyses
      assessed differences between younger and older adolescents and between males and
      females. RESULTS: The 236 participants were an average age of 15.58 years (SD
      1.98), 58% were male, and 60% Caucasian. Average age at injury was 10.57 years
      (SD 5.50), and 62% had paraplegia. For depression, 5.5% of adolescents ages 12 to
      17 years exceeded the clinical cutoff and 12.7% of 18-year-old adolescents fell
      into a range of moderate or severe depression. For anxiety, 10.6% of adolescents
      ages 12 to 18 years exceeded the clinical cutoff. Univariate results revealed
      that older adolescents were more depressed than younger adolescents, and girls
      were more anxious than boys. An interaction between sex and age emerged, in that
      older adolescent girls were significantly more anxious than other youth. Older
      adolescents were also more likely to be taking medications for emotional,
      psychological, or behavioral reasons. Reports of suicidal ideation did not differ
      by adolescent age or sex. CONCLUSION: For these adolescents, depression differed
      with age, and anxiety differed based on age and sex. Implications for
      intervention include early identification and treatment for struggling
      adolescents.

PMID- 24574819
TI  - Depression and depression treatment in women with spinal cord injury.
AB  - BACKGROUND: Research has documented high rates of depression in people with
      spinal cord injury (SCI); however, most SCI research is conducted with
      predominantly male study participants. Additional research is needed on
      depression and depression treatment among women with SCI. OBJECTIVE: Study
      objectives were to examine depression, correlates of depression, and depression
      treatment in a sample of women with SCI. METHODS: The sample included 51
      ethnically and racially diverse women with SCI who participated in a larger study
      on secondary conditions of women with diverse physical disabilities. Recruited
      through health clinics and community organizations in a large metropolitan area,
      participants completed structured interviews that included demographic and
      disability characteristics and measures of health and health care utilization.
      RESULTS: Scores on the Beck Depression Inventory-II (BDI-II) indicated that 41%
      of the women had depressive symptomatology in the mild to severe range. BDI-II
      scores were significantly related to more severe secondary conditions, greater
      pain, and poorer health perceptions but not to demographic or disability
      variables. Nearly a third (n = 16) of the women had scores exceeding the standard
      cutoff for significant clinical depressive symptomatology, yet only 5 of those
      had received any treatment for depression in the past 3 months and only 1 had
      received counseling or psychotherapy. Lifelong depression treatment showed a
      similar pattern of predominantly pharmacologic treatment. CONCLUSION: Depression
      is a common problem for women with SCI, and many do not receive treatment,
      particularly psychological treatment. Disability-sensitive and affordable
      depression treatment must be made available to women with SCI.

PMID- 24574820
TI  - Depression, pain intensity, and interference in acute spinal cord injury.
AB  - BACKGROUND: The high prevalence of pain and depression in persons with spinal
      cord injury (SCI) is well known. However the link between pain intensity,
      interference, and depression, particularly in the acute period of injury, has not
      received sufficient attention in the literature. OBJECTIVE: To investigate the
      relationship of depression, pain intensity, and pain interference in individuals
      undergoing acute inpatient rehabilitation for traumatic SCI. METHODS:
      Participants completed a survey that included measures of depression (PHQ-9),
      pain intensity ("right now"), and pain interference (Brief Pain Inventory:
      general activity, mood, mobility, relations with others, sleep, and enjoyment of
      life). Demographic and injury characteristics and information about current use
      of antidepressants and pre-injury binge drinking also were collected.
      Hierarchical multiple regression was used to test depression models in 3 steps:
      (1) age, gender, days since injury, injury level, antidepressant use, and pre
      injury binge drinking (controlling variables); (2) pain intensity; and (3) pain
      interference (each tested separately). RESULTS: With one exception, pain
      interference was the only statistically significant independent variable in each
      of the final models. Although pain intensity accounted for only 0.2% to 1.2% of
      the depression variance, pain interference accounted for 13% to 26% of the
      variance in depression. CONCLUSION: Our results suggest that pain intensity alone
      is insufficient for understanding the relationship of pain and depression in
      acute SCI. Instead, the ways in which pain interferes with daily life appear to
      have a much greater bearing on depression than pain intensity alone in the acute
      setting.

PMID- 24574821
TI  - Household income and subjective well-being after spinal cord injury: a
      longitudinal study.
AB  - BACKGROUND: Studies regarding subjective well-being (SWB) after spinal cord
      injury (SCI) are increasing in recent years, but little has been contributed to
      the relationship between income and SWB. OBJECTIVE: By using longitudinal data,
      we want to identify (1) the overall trend in SWB over a 10-year period; (2) the
      association between household income and SWB at baseline; (3) the variation of
      the trajectory of SWB over 10 years among different household income groups; and
      (4) the variation of change rates of SWB over 10 years among different household
      income groups. METHODS: We conducted a cohort study, including 434 participants
      who completed 3 measurements in 1998, 2003, and 2008. They were identified from
      outpatient records of 2 midwestern hospitals and a southeastern specialty
      hospital. RESULTS: People with lower household income experienced more life
      problems and less life satisfaction at the baseline measurement. During the 10
      year period, their health problems and environmental barriers significantly
      increased compared to persons with higher income. Increasing vocational
      satisfaction was the only favorable change for the lower income group.
      CONCLUSIONS: There were consistent disparities in SWB related to income, and
      these typically persisted over time. Therefore, with the exception of vocational
      satisfaction, few changes may be anticipated in SWB that would narrow the gap
      between high and low income.

PMID- 24574822
TI  - Impact of an abdominal binder on speech outcomes in people with tetraplegic
      spinal cord injury: perceptual and acoustic measures.
AB  - BACKGROUND: An abdominal binder (AB) is routinely used for patients who have
      suffered a spinal cord injury (SCI) resulting in tetraplegia. It is thought to
      restore abdominal pressure and consequently improve breathing capacity and reduce
      postural hypotension in patients who do not have functioning abdominal muscles.
      OBJECTIVE: To examine the early effects of an AB on respiratory and speech
      outcomes. METHODS: Thirteen individuals who sustained an acute motor complete SCI
      between C3 and T1 were assessed after a 6-week trial of using an elasticized AB
      from the time of first mobilizing in an upright wheelchair. Assessments were made
      using spirometry and perceptual and acoustics speech measures based on sustained
      phonation, sentence recitation, and passage reading. RESULTS: Significant
      improvements were found in the AB-on condition for 3 of 5 respiratory parameters
      (vital capacity, forced vital capacity, and forced expiratory volume in 1
      second). Predominantly mild voice and speech dysfunction were noted in
      participants. No significant difference was found for any of the acoustic and
      perceptual speech parameters (maximum phonation time, vocal intensity for
      sentence recitation, perceptual speech characteristics, or vocal quality) between
      the AB conditions. CONCLUSIONS: Despite the finding that an AB results in
      significant improvements in respiratory function for individuals with tetraplegic
      SCI, the current study did not provide evidence that an AB improves speech
      production.

PMID- 24574823
TI  - Effects of FES-Ambulation Training on Locomotor Function and Health-Related
      Quality of Life in Individuals With Spinal Cord Injury.
AB  - BACKGROUND: The combination of body weight-supported gait training with
      functional electrical stimulation (FES) may provide the optimal stimulus for
      improving overground walking after spinal cord injury (SCI). This potential
      benefit is likely due to the combination of specificity with the maximization of
      muscle contractions. OBJECTIVES: To investigate the effects of 12 weeks of FES
      ambulation on overground walking and health-related quality of life (HRQOL) in
      individuals with SCI. METHODS: Six individuals (60.5 +/- 13.2 years) with SCI (C4
      L3; AIS D; 9.3 +/- 12.0 years post injury), completed a thrice-weekly, 12-week
      FES-ambulation training program. Locomotor function was assessed via the Walking
      Index for Spinal Cord Injury II (WISCI II), the 6-minute walk test (6MWT), the 10
      meter walk test (10MWT), and the body-weight support required during training.
      HRQOL was assessed via the Short Form-36, the Perceived Stress Scale, and the
      Center of Epidemiological Studies for Depression scale. RESULTS: Participants
      showed significant improvements in the 6MWT (223.6 +/- 141.5 m to 297.3 +/- 164.5
      m; P = .03), the required body weight support (55.3% +/- 12.6% to 14.7% +/-
      23.2%; P = .03), and a nonsignificant trend toward an increase in walking speed
      during the 10MWT (0.69 +/- 0.4 m/s to 0.9 +/- 0.5 m/s; P = .08) following the
      training program. Four participants showed improvements on the WISCI II (1-4
      points). Participants also showed a decrease in the Short Form-36 pain score (6.5
      +/- 1.2 to 5.0 +/- 1.7; P = .04) and an increase in the overall mental health
      score (47.8 +/- 12.6 to 54.2 +/- 6.7; P = .04). CONCLUSION: FES-ambulation was
      associated with enhanced overground walking in individuals with AIS D SCI,
      reduced pain, and improved mental health.

PMID- 24574824
TI  - Effect of a cooling vest on core temperature in athletes with and without spinal
      cord injury.
AB  - BACKGROUND: It is well accepted that persons with spinal cord injury (SCI) have
      impaired ability to regulate core temperature due to impaired vasomotor and
      sudomotor activity below their level of injury. Impaired heat dissipation puts
      SCI athletes at great risk of exercise-induced hyperthermia (EIH) (>37.8 degrees
      C). There is minimal evidence for efficacy of any specific cooling method in SCI
      athletes in a thermoneutral sport-specific setting. OBJECTIVE: To evaluate the
      extent of EIH in persons with and without SCI and subsequently examine the effect
      of a cooling vest to attenuate rise in core body temperature (Tc). METHODS: SCI
      (n = 17) and able-bodied (AB; n = 19) athletes participated in a 60-minute
      intermittent sprinting exercise in a thermoneutral (21.1 degrees C-23.9 degrees
      C) environment. Participants were separated according to their level of injury:
      tetraplegia defined as above T1 (TP; n = 6), high paraplegia defined as T5
      through T1 (HP; n = 5), low paraplegia defined as T6 and below (LP; n = 6), and
      AB (n = 19). Tc was recorded at 15-minute intervals using an ingestible
      thermometer pill. This protocol was completed with a cooling vest (V) and without
      a cooling vest (NV). RESULTS: All SCI and most AB athletes experienced EIH. After
      60 minutes, Tc of TP athletes was significantly increased compared to HP (P =
      .03) and AB athletes (P = .007). There was no significant effect of the vest on
      Tc over time for any group. CONCLUSIONS: TP athletes have the highest risk of
      exercise-induced hyperthermia. The cooling vest does not significantly attenuate
      rise in Tc in SCI or AB athletes.

PMID- 24574825
TI  - Safety and Efficacy of Ranolazine for the Treatment of Chronic Angina Pectoris.
AB  - Coronary heart disease is a global malady and it is the leading cause of death in
      the United States. Chronic stable angina is the most common manifestation of
      coronary heart disease and it results from the imbalance between myocardial
      oxygen supply and demand due to reduction in coronary blood flow. Therefore, in
      addition to lifestyle changes, commonly used pharmaceutical treatments for angina
      (nitrates, beta-blockers, Ca2+ channel blockers) are aimed at increasing blood
      flow or decreasing O2 demand. However, patients may continue to experience
      symptoms of angina. Ranolazine is a relatively new drug with anti-anginal and
      anti-arrhythmic effects. Its anti-anginal mechanism is not clearly understood but
      the general consensus is that ranolazine brings about its anti-anginal effects by
      inhibiting the late Na+ current and the subsequent intracellular Ca2+
      accumulation. Recent studies suggest other effects of ranolazine that may explain
      its anti-anginal and anti-arrhythmic effects. Nonetheless, clinical trials have
      proven the efficacy of ranolazine in treating chronic angina. It has been shown
      to be ineffective, however, in treating acute coronary syndrome patients.
      Ranolazine is a safe drug with minimal side effects. It is metabolized mainly in
      the liver and cleared by the kidney. Therefore, caution must be taken in patients
      with impaired hepatic or renal function. Due to its efficacy and safety,
      ranolazine was approved for the treatment of chronic angina by the Food and Drug
      Administration (FDA) in 2006.

PMID- 24574826
TI  - Antiangiogenesis therapy: an update after the first decade.
AB  - Angiogenesis is a complex biological phenomenon that forms new blood vessels from
      the pre-existing vasculature. Aberrant angiogenesis has been implicated in a
      variety of diseases such as cancer, atherosclerosis, arthritis, obesity,
      pulmonary hypertension, diabetic retinopathy, and age-related macular
      degeneration. These conditions collectively affect nearly 10% of the global
      population. Much effort has focused on identifying new therapeutic agents that
      inhibit pathological angiogenesis since 1971, when Judah Folkman published the
      hypothesis that tumor growth is angiogenesis-dependent and that its inhibition
      may be therapeutic. In 2004, the U.S. Food and Drug Administration approved the
      first antiangiogenic drug for the treatment of metastatic colon cancer,
      bevacizumab (Avastin, Genentech). This drug is a humanized monoclonal antibody
      that neutralizes the vascular endothelial growth factor. It is used in
      combination with chemotherapy, and its use began the era of antiangiogenesis
      therapy. Several new therapeutic agents have been added to the list of approved
      drugs, and clinical trials of new therapeutic options and antiangiogenic agents
      are ongoing. This review describes the progress made in the first decade of
      antiangiogenesis therapy, and addresses both validated and possible targets for
      future drug development.

PMID- 24574828
TI  - Oxidative stress, point-of-care test, and metabolic syndrome.

PMID- 24574827
TI  - S100A8/A9 as a biomarker for synovial inflammation and joint damage in patients
      with rheumatoid arthritis.
AB  - S100A8 and S100A9 are major leukocyte proteins, known as damage-associated
      molecular patterns, found at high concentrations in the synovial fluid of
      patients with rheumatoid arthritis (RA). A heterodimeric complex of S100A8/A9 is
      secreted by activated leukocytes and binds to Toll-like receptor 4, which
      mediates downstream signaling and promotes inflammation and autoimmunity. Serum
      and synovial fluid levels of S100A8/A9 are markedly higher in patients with RA
      than in patients with osteoarthritis or miscellaneous inflammatory arthritis.
      Serum levels of S100A8/A9 are significantly correlated with clinical and
      laboratory markers of inflammation, such as C-reactive protein, erythrocyte
      sedimentation rate, rheumatoid factor, and the Disease Activity Score for 28
      joints. Significant correlations have also been found between S100A8/A9 and
      radiographic and clinical assessments of joint damage, such as hand radiographs
      and the Rheumatoid Arthritis Articular Damage score. In addition, among known
      inflammatory markers, S100A8/A9 has the strongest correlation with total sum
      scores of ultrasonography assessment. Furthermore, baseline levels of S100A8/A9
      are independently associated with progression of joint destruction in
      longitudinal studies and are responsive to change during conventional and
      biologic treatments. These findings suggest S100A8/A9 to be a valuable diagnostic
      and prognostic biomarker for RA. 

PMID- 24574829
TI  - Risks associated with sunitinib use and monitoring to improve patient outcomes.

PMID- 24574830
TI  - Third-generation cephalosporin resistance in gram-negative bacteria in the
      community: a growing public health concern.

PMID- 24574831
TI  - Measurement of antioxidant capacity using the biological antioxidant potential
      test and its role as a predictive marker of metabolic syndrome.
AB  - BACKGROUND/AIMS: Oxidative stress increases the risk of cardiovascular
      complications of metabolic syndrome (MetS). This study was conducted to examine
      the difference in antioxidant capacity according to the presence of MetS, and to
      characterize the association between antioxidant capacity and MetS-related
      factors. METHODS: We used the biological antioxidant potential (BAP) test to
      estimate antioxidant capacity. The BAP test has recently been used as an
      indicator of antioxidant capacity. We measured BAP levels in 45 patients with
      MetS (mean age, 44.6 +/- 1.1 years) and 47 age- and sex-matched controls (mean
      age, 42.7 +/- 1.1 years). To evaluate the association between antioxidant
      capacity and MetS, adiponectin, high-sensitivity C-reactive protein (hs-CRP),
      interleukin-6, tumor necrosis factor-alpha, and homeostatic model assessment for
      insulin resistance (HOMA-IR), linear regression and logistic analyses were
      performed. RESULTS: The mean BAP of the MetS group (1,937.3 +/- 36.5 umol/L) was
      significantly lower than that of the non-MetS group (2,101.7 +/- 29.5 umol/L).
      Also, the mean BAP was low in persons having low high density lipoprotein and
      high triglyceride. Reduced antioxidant capacity was significantly associated with
      adiponectin, HOMA-IR and hs-CRP after adjusting for age and sex. The odds ratios
      for MetS with BAP, log adiponectin, log HOMA-IR, and log hs-CRP were 0.63 (95%
      confidence interval [CI], 0.49 to 0.82), 0.22 (0.10 to 0.51), 14.24 (4.35 to
      46.58), and 1.93 (1.36 to 2.75), respectively. CONCLUSIONS: Persons with MetS
      showed reduced antioxidant capacity. We identified relationships between
      antioxidant capacity measured by BAP test and MetS, as well as MetS-related
      factors, such as insulin resistance, hs-CRP, and adiponectin.

PMID- 24574832
TI  - Renal adverse effects of sunitinib and its clinical significance: a single-center
      experience in Korea.
AB  - BACKGROUND/AIMS: Sunitinib is an oral multitargeted tyrosine kinase inhibitor
      used mainly for the treatment of metastatic renal cell carcinoma. The renal
      adverse effects (RAEs) of sunitinib have not been investigated. The aim of this
      study was to determine the incidence and risk factors of RAEs (proteinuria [PU]
      and renal insufficiency [RI]) and to investigate the relationship between PU and
      antitumor efficacy. METHODS: We performed a retrospective review of medical
      records of patients who had received sunitinib for more than 3 months. RESULTS:
      One hundred and fifty-five patients (mean age, 58.7 +/- 12.6 years) were
      enrolled, and the mean baseline creatinine level was 1.24 mg/dL. PU developed in
      15 of 111 patients, and preexisting PU was aggravated in six of 111 patients.
      Only one patient developed typical nephrotic syndrome. Following discontinuation
      of sunitinib, PU was improved in 12 of 17 patients but persisted in five of 17
      patients. RI occurred in 12 of 155 patients, and the maximum creatinine level was
      3.31 mg/dL. RI improved in two of 12 patients but persisted in 10 of 12 patients.
      Risk factors for PU were hypertension, dyslipidemia, and chronic kidney disease.
      Older age was a risk factor for RI. The median progression-free survival was
      significantly better for patients who showed PU. CONCLUSIONS: The incidence of
      RAEs associated with sunitinib was lower than those of previous reports. The
      severity of RAEs was mild to moderate, and partially reversible after cessation
      of sunitinib. We suggest that blood pressure, urinalysis, and renal function in
      patients receiving sunitinib should be monitored closely.

PMID- 24574833
TI  - Third-generation cephalosporin resistance of community-onset Escherichia coli and
      Klebsiella pneumoniae bacteremia in a secondary hospital.
AB  - BACKGROUND/AIMS: To enable appropriate antimicrobial treatment for community
      onset infections in emergency departments (EDs), data are needed on the
      resistance profiles of Escherichia coli and Klebsiella pneumoniae, which are the
      main pathogens of community-onset bacteremia. METHODS: Records were reviewed of
      734 patients with E. coli and K. pneumoniae bacteremia who visited the Daegu
      Fatima Hospital ED, Daegu, Korea between 2003 and 2009. We investigated the
      demographic data, clinical findings, and antimicrobial susceptibility patterns of
      the organisms. RESULTS: Of 1,208 cases of community-onset bacteremia, 62.8% were
      caused by E. coli or K. pneumoniae in an ED of a secondary care hospital. Five
      hundred and forty-eight cases of E. coli (75%) and 183 cases of K. pneumoniae
      (25%) were analyzed. Urinary tract infection (43.1%) was most common, followed by
      intra-abdominal infection (39%) and pneumonia (7.2%).
      Trimethoprim/sulfamethoxazole, fluoroquinolone, third-generation cephalosporin
      (3GC) and amikacin resistance rates among E. coli and K. pneumoniae were 22.8%,
      19.6%, 6.2%, and 1.3%, respectively. In 2009, the rate of 3GC resistance (10.6%)
      was significantly higher, compared to the annual averages of 2003 to 2008 (6.1%;
      p = 0.03). Previous exposure to antibiotics was an independent risk factor for
      3GC resistance in multivariate logistic regression analysis. CONCLUSIONS: The
      rate of 3GC resistance increased in community-onset infections, and previous
      exposure to antibiotics was an independent risk factor. Despite the increased 3GC
      resistance in community-onset infections, an amikacin combination therapy could
      provide an option for treatment of bacteremic patients with previous antibiotic
      exposure in an ED.

PMID- 24574834
TI  - Is propofol safe when administered to cirrhotic patients during sedative
      endoscopy?
AB  - BACKGROUND/AIMS: In patients with liver cirrhosis, drugs acting on the central
      nervous system can lead to hepatic encephalopathy and the effects may be
      prolonged. Recently, misuse of propofol has been reported and the associated risk
      of death have become an issue. Propofol is commonly used during sedative
      endoscopy; therefore, its safety in high-risk groups must be further
      investigated. We performed a pilot study of the safety and efficacy of propofol
      during endoscopy in Korean patients with cirrhosis. METHODS: Upper
      gastrointestinal endoscopy was performed under sedation with propofol along with
      careful monitoring in 20 patients with liver cirrhosis and 20 control subjects.
      The presence or development of hepatic encephalopathy was assessed using the
      number connection test and neurologic examination. RESULTS: Neither respiratory
      depression nor clinically significant hypotension were observed. Immediate
      postanesthetic recovery at 5 and 10 minutes after the procedure was delayed in
      the cirrhotic patients compared with the control group; however, at 30 minutes,
      the postanesthetic recovery was similar in both groups. Baseline psychomotor
      performance was more impaired in cirrhotic patients, but propofol was not
      associated with deteriorated psychomotor function even in cirrhotic patients with
      a minimal hepatic encephalopathy. CONCLUSIONS: Sedation with propofol was well
      tolerated in cirrhotic patients. No newly developed hepatic encephalopathy was
      observed.

PMID- 24574835
TI  - Long-term outcomes of intravascular ultrasound-guided implantation of bare metal
      stents versus drug-eluting stents in primary percutaneous coronary intervention.
AB  - BACKGROUND/AIMS: While drug-eluting stents (DESs) have shown favorable outcomes
      in ST-segment elevation myocardial infarction (STEMI) compared to bare metal
      stents (BMSs), there are concerns about the risk of stent thrombosis (ST) with
      DESs. Because intravascular ultrasound (IVUS) guidance may help optimize stent
      placement and improve outcomes in percutaneous coronary intervention (PCI)
      patients, we evaluated the impact of IVUS-guided BMS versus DES implantation on
      long-term outcomes in primary PCI. METHODS: In all, 239 STEMI patients received
      DES (n = 172) or BMS (n = 67) under IVUS guidance in primary PCI. The 3-year
      incidence of major adverse cardiac events (MACEs) including death, myocardial
      infarction (MI), target vessel revascularization (TVR), and ST was evaluated.
      RESULTS: There was no difference in all cause mortality or MI. However, the
      incidence of TVR was 23.9% with BMS versus 9.3% with DES (p = 0.005). Thus, the
      number of MACEs was significantly lower with DES (11.0% vs. 29.9%; p = 0.001).
      The incidence of definite or probable ST was not different (1.5% vs. 2.3%; p =
      1.0). IVUS-guided DES implantation (hazard ratio [HR], 0.25; 95% confidence
      interval [CI], 0.08 to 0.78; p = 0.017), stent length (HR, 1.03; 95% CI, 1.00 to
      1.06; p = 0.046), and multivessel disease (HR, 3.01; 95% CI, 1.11 to 8.15; p =
      0.030) were independent predictors of MACE. CONCLUSIONS: In patients treated with
      primary PCI under IVUS guidance, the use of DES reduced the incidence of 3-year
      TVR versus BMS. However, all cause mortality and MI were similar between the
      groups. The incidence of ST was low in both groups.

PMID- 24574836
TI  - Poor agreement between QuantiFERON-TB Gold test and tuberculin skin test results
      for the diagnosis of latent tuberculosis infection in rheumatoid arthritis
      patients and healthy controls.
AB  - BACKGROUND/AIMS: We investigated the agreement between the QuantiFERON-TB Gold
      (QFT-Gold) test and the tuberculin skin test (TST) in the diagnosis of latent
      tuberculosis infection in patients with rheumatoid arthritis (RA), compared with
      healthy controls, in Korea. METHODS: We recruited 64 patients with RA and 79
      healthy controls at two university hospitals in South Korea. The participants
      underwent both the QFT-Gold test and the TST simultaneously between August 2006
      and February 2009. All patients were diagnosed using the classification criteria
      for RA revised in 1987 by the American College of Rheumatology. Bacillus Calmette
      Guerin vaccination status and current medications were evaluated, and disease
      activities were assessed using the Disease Activity Score in 28 joints. Eleven
      patients with RA produced indeterminate QFT-Gold test results and were thus
      excluded from the kappa analysis. RESULTS: Based on an induration of 10 mm in
      diameter as the TST cutoff value, the QFT-Gold test and TST demonstrated 75.0%
      agreement (kappa = 0.23) in patients with RA and 75.9% agreement (kappa = 0.19)
      in healthy controls. Among the 56 patients with RA who had negative TST results,
      11 patients (17.2%) also yielded indeterminate QFT-Gold results. CONCLUSIONS: Our
      study showed poor agreement between the results of the QFT-Gold test and the TST
      in both RA patients and healthy controls. Based on these findings, we emphasize
      the importance of making clinical decisions in the diagnosis of latent
      tuberculosis in Koreans with or without RA.

PMID- 24574837
TI  - Clinical features and prognostic factors of Churg-Strauss syndrome.
AB  - BACKGROUND/AIMS: Churg-Strauss syndrome (CSS) is a rare systemic necrotizing
      small-vessel vasculitis, with accompanying bronchial asthma, eosinophilia, and
      eosinophilic infiltration of various tissues. The purposes of our study were to
      characterize the clinical features of CSS and to identify factors associated with
      CSS prognosis in Koreans. METHODS: Medical records were reviewed retrospectively
      for all physician-diagnosed CSS patients in the Seoul National University
      Hospital between January 1990 and March 2011. RESULTS: Data from 52 CSS patients
      were analyzed. The respiratory tract was the most commonly involved organ
      (90.4%). Renal involvement was less frequent in antineutrophilic cytoplasmic
      antibody (ANCA)(-) patients than in ANCA(+) patients (p = 0.048). Clinical
      remission occurred in 95.3% of patients, but 16.3% of them relapsed. Patients who
      maintained remission for more than 6 months were relatively older (median, 51
      years) at diagnosis (p = 0.004), had been diagnosed in earlier stages (p =
      0.027), showed more frequent respiratory involvement (p = 0.024) and generalized
      symptoms (p = 0.039), and showed less frequent cutaneous involvement (p = 0.030)
      than those who did not achieve persistent (> 6 months) remission. Patients who
      achieved persistent remission also showed higher C-reactive protein (CRP) levels
      (p = 0.031) than those who did not. CONCLUSIONS: ANCA(-) CSS patients showed less
      frequent renal involvement. Characteristics of good responders were older age,
      diagnosis at earlier stages, less cutaneous involvement, more respiratory
      involvement, high CRP values, and more generalized symptoms.

PMID- 24574839
TI  - Hepatoduodenal fistula formation following transcatheter arterial
      chemoembolization and radiotherapy for hepatocellular carcinoma: treatment with
      endoscopic Histoacryl injection.
AB  - A 71-year-old male patient was readmitted to our hospital 1 month after discharge
      because of relapse of abdominal pain. He had been diagnosed with hepatocellular
      carcinoma (HCC) 1 year prior and had undergone repeated transcatheter arterial
      chemoembolization and radiotherapy. During the last hospitalization, he was
      diagnosed with a liver abscess complicated by previous treatments for HCC and was
      treated with intravenous antibiotics and abscess aspiration. Follow-up abdominal
      computed tomography revealed a liver abscess with a duodenal fistula, which was
      successfully treated with endoscopic Histoacryl injection into the fistula. Liver
      abscesses with duodenal fistulas rarely occur, but they are intractable and
      possibly fatal in patients with HCC. In the literature, they have frequently been
      managed only with abscess treatment without fistula management. We herein report
      the first case of a patient with a liver abscess complicated by a fistula between
      the duodenum and the abscess, which was treated with endoscopic Histoacryl
      injection. 

PMID- 24574838
TI  - Duodenal adenocarcinoma following a neuroendocrine tumor in the duodenum.
AB  - Primary duodenal adenocarcinoma is a rare malignant neoplasm accounting for 0.3%
      of all gastrointestinal tract carcinomas. We herein present one case of duodenal
      adenocarcinoma after duodenal neuroendocrine carcinoma. Poorly differentiated
      duodenal neuroendocrine carcinoma with liver metastasis (TxNxM1) was confirmed,
      and eight cycles of palliative chemotherapy (5-fluorouracil/etoposide/cisplatin)
      were administered. The patient was then in a clinically complete response status.
      About 1 year later, newly developed adenocarcinoma was detected at the same site.
      It was completely surgically resected, and the patient was cured.

PMID- 24574840
TI  - Spontaneous coronary artery dissection by intravascular ultrasound in a patient
      with myocardial infarction.
AB  - Spontaneous coronary artery dissection is a rare cause of acute coronary syndrome
      and sudden cardiac death. The incidence, causes, pathogenesis, and treatment have
      not been defined clearly, but spontaneous coronary artery dissection should be
      considered in young patients without major cardiovascular risk factors or in
      patients in the peripartum period who present with acute coronary syndrome. The
      treatment is often challenging. Medical treatment is usually considered, and
      percutaneous coronary intervention or coronary artery bypass surgery may be
      possible in some patients. We herein report two cases of middle-aged males with
      myocardial infarction who were treated with percutaneous coronary angioplasty. 

PMID- 24574841
TI  - Hypothermia-induced acute kidney injury in an elderly patient.
AB  - Hypothermia, defined as an unintentional decline in the core body temperature to
      below 35C, is a life-threatening condition. Patients with malnutrition and
      diabetes mellitus as well as those of advanced age are at high risk for
      accidental hypothermia. Due to the high mortality rates of accidental
      hypothermia, proper management is critical for the wellbeing of patients.
      Accidental hypothermia was reported to be associated with acute kidney injury
      (AKI) in over 40% of cases. Although the pathogenesis remains to be elucidated,
      vasoconstriction and ischemia in the kidney were considered to be the main
      mechanisms involved. Cases of AKI associated with hypothermia have been reported
      worldwide, but there have been few reports of hypothermia-induced AKI in Korea.
      Here, we present a case of hypothermia-induced AKI that was treated successfully
      with rewarming and supportive care.

PMID- 24574842
TI  - Diabetic ketoacidosis as a presenting symptom of complicated pancreatic cancer.

PMID- 24574844
TI  - Successful treatment of myelodysplastic syndrome and Behcet colitis after
      allogeneic hematopoietic stem cell transplantation.

PMID- 24574843
TI  - Neuropathic truncal pain in patients with type 2 diabetes mellitus relieved by
      topical cream and nerve block.

PMID- 24574845
TI  - Eosinophilic organ infiltration without eosinophilia or direct parasite
      infection.

PMID- 24574846
TI  - Acupuncture needle: an obscure cause of anal pain.

PMID- 24574847
TI  - Cervical spine fracture in advanced ankylosing spondylitis.

PMID- 24574849
TI  - Review and redescription of species in the Oecetis avara group, with the
      description of 15 new species (Trichoptera, Leptoceridae).
AB  - The O. avara group of Oecetis is formally defined to include 4 described species,
      O. avara (Banks), O. disjuncta (Banks), O. elata Denning & Sykora, and O.
      metlacenis Bueno-Soria, and 15 new species. Oecetis marquesi Bueno-Soria,
      previously considered a member of the O. avara group, is treated as incertae
      sedis to species group, but is also redescribed and treated in the current work.
      New species described here (with their respective distributions) include: O.
      acciptrina (Costa Rica, Panama, Ecuador), O. agosta (Mexico), O. angularis
      (Guatemala to Ecuador), O. apache (SW USA), O. campana (Ecuador), O. constricta
      (Mexico to Ecuador, Venezuela, and Trinidad), O. houghtoni (North America), O.
      maritza (Costa Rica), O. mexicana (Mexico to Ecuador), O. patula (Guatemala,
      Nicaragua), O. protrusa (Mexico to Ecuador), O. sordida (Mexico, USA, Canada), O.
      tumida (Costa Rica), O. uncata (Costa Rica), and O. verrucula (Mexico to Costa
      Rica). A key to the species is also provided. 

PMID- 24574850
TI  - A new subspecies of Nitokra affinis Gurney, 1927 (Copepoda, Harpacticoida) from
      the Caribbean coast of Colombia.
AB  - Plankton samples from Laguna Navio Quebrado, La Guajira, northern Colombia,
      yielded male and female specimens of an harpacticoid copepod that was first
      identified as the widely distributed species Nitokra affinis Gurney, 1927 for
      which at least four subspecies have been described from different geographic
      areas. A more detailed examination of the Colombian specimens revealed that it
      differs from the other morphs so far considered as subspecies. The Colombian
      specimens differ from the other four known subspecies in the following aspects:
      (1) rostrum with long projection, (2) relatively long exopod of P1, almost as
      long as first endopodal segment, (3) endopodal and exopodal rami of P2 equally
      long, (4) a reduced number of endopodal setal elements of the male P5. It also
      differs from N. a. californica Lang in details of the ornamentation of the
      urosomites. Descriptions and illustrations of this new subspecies, the first one
      described from the Neotropical region, are presented together with a key to the
      five known subspecies of Nitokra affinis. As in many other cases of presumedly
      widespread species of harpacticoids, it is possible that N. affinis represents a
      species complex with more restricted distributional patterns, a notion that
      certainly deserves further study. 

PMID- 24574851
TI  - Nannodromus reveilleti (Acari, Anystida, Saxidromidae) a new genus and species
      from South Africa.
AB  - The description of a new genus Nannodromus and a new species Nannodromus
      reveilleti (Acari: Anystides: Saxidromidae) from South Africa, based on adult
      males and females. 

PMID- 24574852
TI  - Description of Oculogryphus shuensis sp. n. (Coleoptera, Lampyridae), the first
      species of the genus in the Sino-Japanese realm, with a modified key to the
      subfamily Ototretinae.
AB  - A new species of the lampyrid genus Oculogryphus Jeng, Engel, and Yang, O.
      shuensis sp. n. from China (Sichuan Province) is described and figured. The genus
      previously was known only from Vietnam, and the new species is the first
      representative of the genus in the Sino-Japanese zoogeographic realm. Some
      morphological variations of Oculogryphus and the allied genus Stenocladius are
      discussed and a modification to the most recent key to ototretine genera is
      proposed to accommodate Oculogryphus. 

PMID- 24574848
TI  - Severe influenza treatment guideline.

PMID- 24574853
TI  - A taxonomic study of Chinese species of the insidiosus group of Metaphycus
      (Hymenoptera, Encyrtidae).
AB  - In this paper, twelve insidiosus-group species of the genus Metaphycus Mercet
      from China are reviewed. Five species, M. corniae sp. n., M. cylindricus sp. n.,
      M. deltoideus sp. n., M. transversus sp. n. and M. yaanensis sp. n., are
      described as new to science. A key to the females of these species is given to
      facilitate species recognition. Photomicrographs are provided to illustrate
      morphological characters of these species. All specimens, unless otherwise
      specified, are deposited in the National Zoological Museum of China, Institute of
      Zoology, Chinese Academy of Sciences, Beijing. 

PMID- 24574854
TI  - Morphological and molecular characterization of a new species of leech
      (Glossiphoniidae, Hirudinida): Implications for the health of its imperiled
      amphibian host (Cryptobranchus alleganiensis).
AB  - The hellbender (Cryptobranchus alleganiensis) is among the most intriguing and
      imperiled amphibians in North America. Since the 1970s and 80s, western
      populations of the Ozark and eastern subspecies in Missouri have declined by
      nearly 80%. As a result of population declines, the Ozark hellbender was recently
      federally protected as an endangered species, and the eastern subspecies was
      granted protection under CITES. Although habitat degradation is probably the
      biggest threat to hellbender populations, recent evidence suggests that pathogens
      including chytrid fungus and "flesh-eating" bacteria may also contribute to
      declines in Ozark hellbenders. Leeches, which are very common on Ozark
      hellbenders, have recently been implicated as possible vectors of disease among
      Ozark hellbenders but have not been described in eastern hellbenders or outside
      of Missouri and Arkansas. We discovered a population of leeches on eastern
      hellbenders in southwest Virginia and confirmed that the species of leech is
      within the genus Placobdella, but is morphologically and genetically distinct
      from all previously described leech species. We named the new species Placobdella
      appalachiensis sp. n. Moser and Hopkins, based on the mountainous region in which
      it was discovered. Our surveys over a three consecutive year period suggested
      that this leech species may be patchily distributed and/or have a narrow
      geographic range. We consistently detected leeches at one site (mean prevalence
      in 80 hellbenders = 27.5%; median intensity = 3.0 leeches per parasitized
      hellbender [range 1 - >250 leeches]) during three years of surveys, but we never
      found leeches in any of our other seven study sites in two streams (mean
      prevalence in 139 hellbenders = 0%). We found a significant positive relationship
      between hellbender body size and the intensity of parasitism, and we suggest the
      possibility that the behavioral ecology of adults leading up to reproduction may
      increase their encounter rates with parasites. We discuss the potential
      conservation implications of discovery of leeches in this stream, and make
      recommendations for future mitigation and monitoring efforts. 

PMID- 24574855
TI  - Revision of the genus Reichardtiolus Kryzhanovskij, 1959 (Coleoptera, Histeridae,
      Saprininae).
AB  - The genus Reichardtiolus Kryzhanovskij, 1959 is revised herein. It now contains
      five species: R. duriculus (Reitter, 1904) from middle Asia (with a doubtful
      female specimen from western China that is here tentatively assigned to this
      species), R. pavlovskii Kryzhanovskij, 1959 from Turkmenistan, R. sphingis
      (Peyerimhoff, 1936), comb. n. (transferred from Saprinus Erichson, 1834) from
      Egypt and Jordan, R. perses sp. n. from Iran and R. aldhaferi sp. n. from Saudi
      Arabia. Except for R. pavlovskii, which is a rather distinct species known only
      from two females, the remaining species are allopatric, very similar externally
      and are best separated from each other by their male terminalia. R. pavlovskii is
      kept in Reichardtiolus only tentatively, pending the examination of more
      specimens, and especially its male genitalia. R. duriculus and R. pavlovskii are
      re-described, while R. perses sp. n., R. aldhaferi sp. n. and R. sphingis comb.
      n. are provided with diagnostic descriptions because of their overall similarity
      with R. duriculus. Morphological differences of all species are illustrated using
      SEM micrographs. Male genitalia of R. duriculus, R. sphingis comb. n., R. perses
      sp. n. and R. aldhaferi sp. n. are illustrated and a key to the species is given.
      R. duriculus is newly recorded from Tajikistan. 

PMID- 24574856
TI  - Darwin's legacy to rove beetles (Coleoptera, Staphylinidae): A new genus and a
      new species, including materials collected on the Beagle's voyage.
AB  - A species of xanthopygine rove beetles is described and figured here as
      Darwinilus sedarisi gen. n. and sp. n. The holotype was collected by Charles
      Darwin in Bahia Blanca, Argentina on the Beagle's voyage. The contributions of
      Charles Darwin to rove beetle systematics are summarized briefly. 

PMID- 24574857
TI  - A new Hermeuptychia (Lepidoptera, Nymphalidae, Satyrinae) is sympatric and
      synchronic with H. sosybius in southeast US coastal plains, while another new
      Hermeuptychia species - not hermes - inhabits south Texas and northeast Mexico.
AB  - Hermeuptychia intricata Grishin, sp. n. is described from the Brazos Bend State
      Park in Texas, United States, where it flies synchronously with Hermeuptychia
      sosybius (Fabricius, 1793). The two species differ strongly in both male and
      female genitalia and exhibit 3.5% difference in the COI barcode sequence of
      mitochondrial DNA. Setting such significant genitalic and genotypic differences
      aside, we were not able to find reliable wing pattern characters to tell a
      difference between the two species. This superficial similarity may explain why
      H. intricata, only distantly related to H. sosybius, has remained unnoticed until
      now, despite being widely distributed in the coastal plains from South Carolina
      to Texas, USA (and possibly to Costa Rica). Obscuring the presence of a cryptic
      species even further, wing patterns are variable in both butterflies and ventral
      eyespots vary from large to almost absent. To avoid confusion with the new
      species, neotype for Papilio sosybius Fabricius, 1793, a common butterfly that
      occurs across northeast US, is designated from Savannah, Georgia, USA. It secures
      the universally accepted traditional usage of this name. Furthermore, we find
      that DNA barcodes of Hermeuptychia specimens from the US, even those from extreme
      south Texas, are at least 4% different from those of H. hermes (Fabricius, 1775)
      type locality Brazil: Rio de Janeiro-and suggest that the name H. hermes should
      not be used for USA populations, but rather reserved for the South American
      species. This conclusion is further supported by comparison of male genitalia.
      However, facies, genitalia and 2.1% different DNA barcodes set Hermeuptychia
      populations in the lower Rio Grande Valley of Texas apart from H. sosybius. These
      southern populations, also found in northeastern Mexico, are described here as
      Hermeuptychia hermybius Grishin, sp. n. (type locality Texas: Cameron County).
      While being phylogenetically closer to H. sosybius than to any other
      Hermeuptychia species, H. hermybius can usually be recognized by wing patterns,
      such as the size of eyespots and the shape of brown lines on hindwing. "Intricate
      Satyr" and "South Texas Satyr" are proposed as the English names for H. intricata
      and H. hermybius, respectively. 

PMID- 24574858
TI  - A new cryptic Sympistis from eastern North America revealed by novel larval
      phenotype and host plant association (Lepidoptera, Noctuidae, Oncocnemidinae).
AB  - A Triosteum-feeding species of Sympistis is described from eastern North America:
      Sympistis forbesi sp. n. Identity of the new species is most reliably determined
      from larval morphology and host plant association-both adult scaling and
      genitalic characters overlap with those of Sympisitis chionanthi, a Chionanthus
      and Fraxinus feeder. 

PMID- 24574859
TI  - Lyngbyabellins K-N from Two Palmyra Atoll Collections of the Marine
      Cyanobacterium Moorea bouillonii.
AB  - Five lipopeptides of the lyngbyabellin structure class, four cyclic (1-3, and 5)
      and one linear (4), were isolated from the extracts of two collections of
      filamentous marine cyanobacteria obtained from Palmyra Atoll in the Central
      Pacific Ocean. Their planar structures and absolute configurations were
      elucidated by combined spectroscopic and chromatographic analyses as well as
      chemical synthesis of fragments. In addition to structural features typical of
      the lyngbyabellins, such as two thiazole rings and a chlorinated 2
      methyloctanoate residue, these new compounds possess several unique aspects. Of
      note, metabolites 2 and 3 possessed rare mono-chlorination on the 3-acyloxy-2
      methyloctanoate residue while lyngbyabellin N (5) had an unusual N,N
      dimethylvaline terminus. Lyngbyabellin N also possessed a leucine statine
      residue, and showed strong cytotoxic activity against HCT116 colon cancer cell
      line (IC50 = 40.9 +/- 3.3 nM).

PMID- 24574861
TI  - Reconfiguration and search of social networks.
AB  - Social networks tend to exhibit some topological characteristics different from
      regular networks and random networks, such as shorter average path length and
      higher clustering coefficient, and the node degree of the majority of social
      networks obeys exponential distribution. Based on the topological characteristics
      of the real social networks, a new network model which suits to portray the
      structure of social networks was proposed, and the characteristic parameters of
      the model were calculated. To find out the relationship between two people in the
      social network, and using the local information of the social network and the
      parallel mechanism, a hybrid search strategy based on k-walker random and a high
      degree was proposed. Simulation results show that the strategy can significantly
      reduce the average number of search steps, so as to effectively improve the
      search speed and efficiency. 

PMID- 24574863
TI  - Vulnerability assessment of IPv6 websites to SQL injection and other application
      level attacks.
AB  - Given the proliferation of internet connected devices, IPv6 has been proposed to
      replace IPv4. Aside from providing a larger address space which can be assigned
      to internet enabled devices, it has been suggested that the IPv6 protocol offers
      increased security due to the fact that with the large number of addresses
      available, standard IP scanning attacks will no longer become feasible. However,
      given the interest in attacking organizations rather than individual devices,
      most initial points of entry onto an organization's network and their attendant
      devices are visible and reachable through web crawling techniques, and,
      therefore, attacks on the visible application layer may offer ways to compromise
      the overall network. In this evaluation, we provide a straightforward
      implementation of a web crawler in conjunction with a benign black box
      penetration testing system and analyze the ease at which SQL injection attacks
      can be carried out. 

PMID- 24574862
TI  - Application of the support vector machine to predict subclinical mastitis in
      dairy cattle.
AB  - This study presented a potentially useful alternative approach to ascertain the
      presence of subclinical and clinical mastitis in dairy cows using support vector
      machine (SVM) techniques. The proposed method detected mastitis in a cross
      sectional representative sample of Holstein dairy cattle milked using an
      automatic milking system. The study used such suspected indicators of mastitis as
      lactation rank, milk yield, electrical conductivity, average milking duration,
      and control season as input data. The output variable was somatic cell counts
      obtained from milk samples collected monthly throughout the 15 months of the
      control period. Cattle were judged to be healthy or infected based on those
      somatic cell counts. This study undertook a detailed scrutiny of the SVM
      methodology, constructing and examining a model which showed 89% sensitivity, 92%
      specificity, and 50% error in mastitis detection. 

PMID- 24574865
TI  - Approximate solution of Urysohn integral equations using the Adomian
      decomposition method.
AB  - We apply Adomian decomposition method (ADM) for obtaining approximate series
      solution of Urysohn integral equations. The ADM provides a direct recursive
      scheme for solving such problems approximately. The approximations of the
      solution are obtained in the form of series with easily calculable components.
      Furthermore, we also discuss the convergence and error analysis of the ADM.
      Moreover, three numerical examples are included to demonstrate the accuracy and
      applicability of the method. 

PMID- 24574866
TI  - A modified nonlinear damage accumulation model for fatigue life prediction
      considering load interaction effects.
AB  - Many structures are subjected to variable amplitude loading in engineering
      practice. The foundation of fatigue life prediction under variable amplitude
      loading is how to deal with the fatigue damage accumulation. A nonlinear fatigue
      damage accumulation model to consider the effects of load sequences was proposed
      in earlier literature, but the model cannot consider the load interaction
      effects, and sometimes it makes a major error. A modified nonlinear damage
      accumulation model is proposed in this paper to account for the load interaction
      effects. Experimental data of two metallic materials are used to validate the
      proposed model. The agreement between the model prediction and experimental data
      is observed, and the predictions by proposed model are more possibly in
      accordance with experimental data than that by primary model and Miner's rule.
      Comparison between the predicted cumulative damage by the proposed model and an
      existing model shows that the proposed model predictions can meet the accuracy
      requirement of the engineering project and it can be used to predict the fatigue
      life of welded aluminum alloy joint of Electric Multiple Units (EMU); meanwhile,
      the accuracy of approximation can be obtained from the proposed model though more
      simple computing process and less material parameters calling for extensive
      testing than the existing model. 

PMID- 24574864
TI  - The incidence and predictors of thromboembolic events in patients with lung
      cancer.
AB  - Patients with lung cancer experience elevated risk of venous thromboembolism.
      Cancer patients with thrombosis have a shorter life expectancy and the occurrence
      of VTE worsens the quality of life and may delay, interrupt, or completely halt
      the cancer therapy. In a large cohort of lung cancer patients we monitored the
      incidence of venous thromboembolism and we identified groups of patients with the
      highest risk of venous thromboembolism suitable for antithrombotic prophylaxis,
      which could favourably affect their morbidity and mortality. 

PMID- 24574860
TI  - Targeted therapies in development for non-small cell lung cancer.
AB  - The iterative discovery in various malignancies during the past decades that a
      number of aberrant tumorigenic processes and signal transduction pathways are
      mediated by "druggable" protein kinases has led to a revolutionary change in drug
      development. In non-small cell lung cancer (NSCLC), the ErbB family of receptors
      (e.g., EGFR [epidermal growth factor receptor], HER2 [human epidermal growth
      factor receptor 2]), RAS (rat sarcoma gene), BRAF (v-raf murine sarcoma viral
      oncogene homolog B1), MAPK (mitogen-activated protein kinase) c-MET (c
      mesenchymal-epithelial transition), FGFR (fibroblast growth factor receptor),
      DDR2 (discoidin domain receptor 2), PIK3CA (phosphatidylinositol-4,5
      bisphosphate3-kinase, catalytic subunit alpha)), PTEN (phosphatase and tensin
      homolog), AKT (protein kinase B), ALK (anaplastic lym phoma kinase), RET
      (rearranged during transfection), ROS1 (reactive oxygen species 1) and EPH
      (erythropoietin-producing hepatoma) are key targets of various agents currently
      in clinical development. These oncogenic targets exert their selective growth
      advantage through various intercommunicating pathways, such as through
      RAS/RAF/MEK, phosphoinositide 3-kinase/AKT/mammalian target of rapamycin and SRC
      signal transduction and transcription signaling. The recent clinical studies,
      EGFR tyrosine kinase inhibitors and crizotinib were considered as strongly
      effective targeted therapies in metastatic NSCLC. Currently, five molecular
      targeted agents were approved for treatment of advanced NSCLC: Gefitinib,
      erlotinib and afatinib for positive EGFR mutation, crizotinib for positive
      echinoderm microtubule-associated protein-like 4 (EML4)-ALK translocation and
      bevacizumab. Moreover, oncogenic mutant proteins are subject to regulation by
      protein trafficking pathways, specifically through the heat shock protein 90
      system. Drug combinations affecting various nodes in these signaling and
      intracellular processes are predicted and demonstrated to be synergistic and
      advantageous in overcoming treatment resistance compared with monotherapy
      approaches. Understanding the role of the tumor microenvironment in the
      development and maintenance of the malignant phenotype provided additional
      therapeutic approaches as well. More recently, improved knowledge on tumor
      immunology has set the stage for promising immunotherapies in NSCLC. This review
      will focus on the rationale for the development of targeted therapies in NSCLC
      and the various strategies employed in preventing or overcoming the inevitable
      occurrence of treatment resistance. 

PMID- 24574867
TI  - Development of hybrid braided composite rods for reinforcement and health
      monitoring of structures.
AB  - In the present study, core-reinforced braided composite rods (BCRs) were
      developed and characterized for strain sensing capability. A mixture of carbon
      and glass fibre was used in the core, which was surrounded by a braided cover of
      polyester fibres. Three compositions of core with different carbon fibre/glass
      fibre weight ratios (23/77, 47/53, and 100/0) were studied to find out the
      optimum composition for both strain sensitivity and mechanical performance. The
      influence of carbon fibre positioning in BCR cross-section on the strain sensing
      behaviour was also investigated. Strain sensing property of BCRs was
      characterized by measuring the change in electrical resistance with flexural
      strain. It was observed that BCRs exhibited increase (positive response) or
      decrease (negative response) in electrical resistance depending on carbon fibre
      positioning. The BCR with lowest amount of carbon fibre was found to give the
      best strain sensitivity as well as the highest tensile strength and breaking
      extension. The developed BCRs showed reversible strain sensing behaviour under
      cyclic flexural loading with a maximum gauge factor of 23.4 at very low strain
      level (0.55%). Concrete beams reinforced with the optimum BCR (23/77) also
      exhibited strain sensing under cyclic flexural strain, although the
      piezoresistive behaviour in this case was irreversible. 

PMID- 24574868
TI  - Performance analysis of a semiactive suspension system with particle swarm
      optimization and fuzzy logic control.
AB  - This paper uses a quarter model of an automobile having passive and semiactive
      suspension systems to develop a scheme for an optimal suspension controller. Semi
      active suspension is preferred over passive and active suspensions with regard to
      optimum performance within the constraints of weight and operational cost. A
      fuzzy logic controller is incorporated into the semi-active suspension system. It
      is able to handle nonlinearities through the use of heuristic rules. Particle
      swarm optimization (PSO) is applied to determine the optimal gain parameters for
      the fuzzy logic controller, while maintaining within the normalized ranges of the
      controller inputs and output. The performance of resulting optimized system is
      compared with different systems that use various control algorithms, including a
      conventional passive system, choice options of feedback signals, and damping
      coefficient limits. Also, the optimized semi-active suspension system is
      evaluated for its performance in relation to variation in payload. Furthermore,
      the systems are compared with respect to the attributes of road handling and ride
      comfort. In all the simulation studies it is found that the optimized fuzzy logic
      controller surpasses the other types of control. 

PMID- 24574870
TI  - Hybrid network defense model based on fuzzy evaluation.
AB  - With sustained and rapid developments in the field of information technology, the
      issue of network security has become increasingly prominent. The theme of this
      study is network data security, with the test subject being a classified and
      sensitive network laboratory that belongs to the academic network. The analysis
      is based on the deficiencies and potential risks of the network's existing
      defense technology, characteristics of cyber attacks, and network security
      technologies. Subsequently, a distributed network security architecture using the
      technology of an intrusion prevention system is designed and implemented. In this
      paper, first, the overall design approach is presented. This design is used as
      the basis to establish a network defense model, an improvement over the
      traditional single-technology model that addresses the latter's inadequacies.
      Next, a distributed network security architecture is implemented, comprising a
      hybrid firewall, intrusion detection, virtual honeynet projects, and connectivity
      and interactivity between these three components. Finally, the proposed security
      system is tested. A statistical analysis of the test results verifies the
      feasibility and reliability of the proposed architecture. The findings of this
      study will potentially provide new ideas and stimuli for future designs of
      network security architecture. 

PMID- 24574869
TI  - The additional information of bitewing radiographs in the detection of
      established or severe dentinal decay in 14-year olds: a cross-sectional study in
      low-caries population.
AB  - AIM: To reveal the additional value of radiographic bitewings (BW) in detection
      of caries and in comparing the occurrence of clinically undetected severe decay
      between 14-year olds with and without clinically observed dentinal caries in a
      low-caries prevalence population. DESIGN: The cross-sectional study used 363
      pairs of radiographs read by one examiner without knowledge of the clinical
      findings. The yield was analyzed on a tooth surface level by cross tabulating the
      clinical and radiographic information and on an individual level by counting the
      number of yield surfaces for all subjects. Mann-Whitney U test was used. RESULTS:
      On a tooth surface level, the contribution of BW was the greatest on the occlusal
      surfaces of the first molars, where established or severe dentinal decay was
      registered in BW in 11% of clinically sound surfaces and in 40% of established
      cavitated enamel lesions. On an individual level, 53% of subjects benefited from
      BW. The subjects clinically DMFS > 0 benefited more than the clinically DMFS = 0
      subjects (P = .004), nearly 60% in relation to 47%, respectively. CONCLUSIONS: In
      a low-caries prevalence population a remarkable portion of both clinically DMFS =
      0 and DMFS > 0 14-year olds benefit from BW examination. Most of the benefit is
      obtained on the occlusal surfaces of the first and the second permanent molars.

PMID- 24574871
TI  - A new system of skip-lot sampling plans including resampling.
AB  - Skip-lot sampling plans have been widely used in industries to reduce the
      inspection efforts when products have good quality records. These schemes are
      known as economically advantageous and useful to minimize the cost of the
      inspection of the final lots. A new system of skip-lot sampling plan called SkSP
      R is proposed in this paper. The performance measures for the proposed SkSP-R
      plan are derived using the Markov chain formulation. The proposed plan is found
      to be more efficient than the single sampling plan and the SkSP-2 plan. 

PMID- 24574872
TI  - Infinitely many weak solutions of the p-Laplacian equation with nonlinear
      boundary conditions.
AB  - We study the following p-Laplacian equation with nonlinear boundary conditions: 
      Delta(p)u + MU(x)|u|(p-2)u = f(x,u) + g(x,u),x ? Omega, | ?u|(p-2)?u/?n =
      eta|u|(p-2)u and x ? ?Omega, where Omega is a bounded domain in R(N) with smooth
      boundary ?Omega. We prove that the equation has infinitely many weak solutions by
      using the variant fountain theorem due to Zou (2001) and f, g do not need to
      satisfy the (P.S) or (P.S*) condition.

PMID- 24574873
TI  - Evaluation of antioxidant and DNA damage protection activity of the
      hydroalcoholic extract of Desmostachya bipinnata L. Stapf.
AB  - Desmostachya bipinnata Stapf (Poaceae/Gramineae) is an official drug of ayurvedic
      pharmacopoeia. Various parts of this plant were used extensively in traditional
      and folklore medicine to cure various human ailments. The present study was aimed
      to evaluate the antioxidant and DNA damage protection activity of hydroalcoholic
      extract of Desmostachya bipinnata both in vitro and in vivo, to provide
      scientific basis for traditional usage of this plant. The extract showed
      significant antioxidant activity in a dose-dependent manner with an IC50 value of
      264.18+/-3.47  MUg/mL in H2O2 scavenging assay and prevented the oxidative damage
      to DNA in presence of DNA damaging agent (Fenton's reagent) at a concentration of
      50  MUg/mL. Also, the presence of extract protected yeast cells in a dose
      dependent manner against DNA damaging agent (Hydroxyurea) in spot assay.
      Moreover, the presence of extract exhibited significant antioxidant activity in
      vivo by protecting yeast cells against oxidative stressing agent (H2O2).
      Altogether, the results of current study revealed that Desmostachya bipinnata is
      a potential source of antioxidants and lends pharmacological credence to the
      ethnomedical use of this plant in traditional system of medicine, justifying its
      therapeutic application for free-radical-induced diseases.

PMID- 24574874
TI  - Mathematical model of solid food pasteurization by ohmic heating: influence of
      process parameters.
AB  - Pasteurization of a solid food undergoing ohmic heating has been analysed by
      means of a mathematical model, involving the simultaneous solution of Laplace's
      equation, which describes the distribution of electrical potential within a food,
      the heat transfer equation, using a source term involving the displacement of
      electrical potential, the kinetics of inactivation of microorganisms likely to be
      contaminating the product. In the model, thermophysical and electrical properties
      as function of temperature are used. Previous works have shown the occurrence of
      heat loss from food products to the external environment during ohmic heating.
      The current model predicts that, when temperature gradients are established in
      the proximity of the outer ohmic cell surface, more cold areas are present at
      junctions of electrodes with lateral sample surface. For these reasons, colder
      external shells are the critical areas to be monitored, instead of internal
      points (typically geometrical center) as in classical pure conductive heat
      transfer. Analysis is carried out in order to understand the influence of
      pasteurisation process parameters on this temperature distribution. A successful
      model helps to improve understanding of these processing phenomenon, which in
      turn will help to reduce the magnitude of the temperature differential within the
      product and ultimately provide a more uniformly pasteurized product. 

PMID- 24574875
TI  - The effect of crumb rubber particle size to the optimum binder content for open
      graded friction course.
AB  - The main objective of this paper is to investigate the relations of rubber size,
      rubber content, and binder content in determination of optimum binder content for
      open graded friction course (OGFC). Mix gradation type B as specified in
      Specification for Porous Asphalt produced by the Road Engineering Association of
      Malaysia (REAM) was used in this study. Marshall specimens were prepared with
      four different sizes of rubber, namely, 20 mesh size [0.841 mm], 40 mesh [0.42
      mm], 80 mesh [0.177 mm], and 100 mesh [0.149 mm] with different concentrations of
      rubberised bitumen (4%, 8%, and 12%) and different percentages of binder content
      (4%-7%). The appropriate optimum binder content is then selected according to the
      results of the air voids, binder draindown, and abrasion loss test. Test results
      found that crumb rubber particle size can affect the optimum binder content for
      OGFC.

PMID- 24574876
TI  - Practical stability in terms of two measures for set differential equations on
      time scales.
AB  - We present a new comparison principle by introducing a notion of upper quasi
      monotone nondecreasing and obtain the practical stability criteria for set valued
      differential equations in terms of two measures on time scales by using the
      vector Lyapunov function together with the new comparison principle. 

PMID- 24574877
TI  - Detecting image splicing using merged features in chroma space.
AB  - Image splicing is an image editing method to copy a part of an image and paste it
      onto another image, and it is commonly followed by postprocessing such as
      local/global blurring, compression, and resizing. To detect this kind of forgery,
      the image rich models, a feature set successfully used in the steganalysis is
      evaluated on the splicing image dataset at first, and the dominant submodel is
      selected as the first kind of feature. The selected feature and the DCT Markov
      features are used together to detect splicing forgery in the chroma channel,
      which is convinced effective in splicing detection. The experimental results
      indicate that the proposed method can detect splicing forgeries with lower error
      rate compared to the previous literature. 

PMID- 24574878
TI  - Preparation and mechanical properties of graphene oxide: cement nanocomposites.
AB  - We investigate the performance of graphene oxide (GO) in improving mechanical
      properties of cement composites. A polycarboxylate superplasticizer was used to
      improve the dispersion of GO flakes in the cement. The mechanical strength of
      graphene-cement nanocomposites containing 0.1-2 wt% GO and 0.5 wt%
      superplasticizer was measured and compared with that of cement prepared without
      GO. We found that the tensile strength of the cement mortar increased with GO
      content, reaching 1.5%, a 48% increase in tensile strength. Ultra high-resolution
      field emission scanning electron microscopy (FE-SEM) used to observe the fracture
      surface of samples containing 1.5 wt% GO indicated that the nano-GO flakes were
      well dispersed in the matrix, and no aggregates were observed. FE-SEM observation
      also revealed good bonding between the GO surfaces and the surrounding cement
      matrix. In addition, XRD diffraction data showed growth of the calcium silicate
      hydrates (C-S-H) gels in GO cement mortar compared with the normal cement mortar.

PMID- 24574879
TI  - Analytical solution for the free vibration analysis of delaminated Timoshenko
      beams.
AB  - This work presents a method to find the exact solutions for the free vibration
      analysis of a delaminated beam based on the Timoshenko type with different
      boundary conditions. The solutions are obtained by the method of Lagrange
      multipliers in which the free vibration problem is posed as a constrained
      variational problem. The Legendre orthogonal polynomials are used as the beam
      eigenfunctions. Natural frequencies and mode shapes of various Timoshenko beams
      are presented to demonstrate the efficiency of the methodology. 

PMID- 24574880
TI  - A real-time apple grading system using multicolor space.
AB  - This study was focused on the multicolor space which provides a better
      specification of the color and size of the apple in an image. In the study, a
      real-time machine vision system classifying apples into four categories with
      respect to color and size was designed. In the analysis, different color spaces
      were used. As a result, 97% identification success for the red fields of the
      apple was obtained depending on the values of the parameter "a" of CIE
      L*a*b*color space. Similarly, 94% identification success for the yellow fields
      was obtained depending on the values of the parameter y of CIE XYZ color space.
      With the designed system, three kinds of apples (Golden, Starking, and Jonagold)
      were investigated by classifying them into four groups with respect to two
      parameters, color and size. Finally, 99% success rate was achieved in the
      analyses conducted for 595 apples. 

PMID- 24574881
TI  - Cyanuric chloride as an efficient catalyst for the synthesis of 2,3-unsaturated O
      glycosides by Ferrier rearrangement.
AB  - Cyanuric chloride has been found to be an efficient catalyst for the synthesis of
      2,3-unsaturated O-glycosides from the reaction of 3,4,6-tri-O-acetyl-D-glucal and
      a wide range of alcohols in dichloromethane at room temperature. The experimental
      procedure is simple, and the products are obtained in high yields. 

PMID- 24574882
TI  - Modified projection algorithms for solving the split equality problems.
AB  - The split equality problem (SEP) has extraordinary utility and broad
      applicability in many areas of applied mathematics. Recently, Byrne and Moudafi
      (2013) proposed a CQ algorithm for solving it. In this paper, we propose a
      modification for the CQ algorithm, which computes the stepsize adaptively and
      performs an additional projection step onto two half-spaces in each iteration. We
      further propose a relaxation scheme for the self-adaptive projection algorithm by
      using projections onto half-spaces instead of those onto the original convex
      sets, which is much more practical. Weak convergence results for both algorithms
      are analyzed. 

PMID- 24574883
TI  - An enhanced informed watermarking scheme using the posterior hidden Markov model.
AB  - Designing a practical watermarking scheme with high robustness, feasible
      imperceptibility, and large capacity remains one of the most important research
      topics in robust watermarking. This paper presents a posterior hidden Markov
      model (HMM-) based informed image watermarking scheme, which well enhances the
      practicability of the prior-HMM-based informed watermarking with favorable
      robustness, imperceptibility, and capacity. To make the encoder and decoder use
      the (nearly) identical posterior HMM, each cover image at the encoder and each
      received image at the decoder are attacked with JPEG compression at an
      equivalently small quality factor (QF). The attacked images are then employed to
      estimate HMM parameter sets for both the encoder and decoder, respectively.
      Numerical simulations show that a small QF of 5 is an optimum setting for
      practical use. Based on this posterior HMM, we develop an enhanced posterior-HMM
      based informed watermarking scheme. Extensive experimental simulations show that
      the proposed scheme is comparable to its prior counterpart in which the HMM is
      estimated with the original image, but it avoids the transmission of the prior
      HMM from the encoder to the decoder. This thus well enhances the practical
      application of HMM-based informed watermarking systems. Also, it is demonstrated
      that the proposed scheme has the robustness comparable to the state-of-the-art
      with significantly reduced computation time. 

PMID- 24574884
TI  - Dependence of performance of Si nanowire solar cells on geometry of the
      nanowires.
AB  - The dependence of performance of silicon nanowires (SiNWs) solar cells on the
      growth condition of the SiNWs has been described. Metal-assisted electroless
      etching (MAE) technique has been used to grow SiNWs array. Different
      concentration of aqueous solution containing AgNO3 and HF for Ag deposition is
      used. The diameter and density of SiNWs are found to be dependent on
      concentration of solution used for Ag deposition. The diameter and density of
      SiNWs have been used to calculate the filling ratio of the SINWs arrays. The
      filling ratio is increased with increase in AgNO3 concentration, whereas it is
      decreased with increase in HF concentration. The minimum reflectance value
      achieved is ~1% for SiNWs of length of ~1.2 MU m in the wavelength range of 300
      1000 nm. The performance and diode parameters strongly depend on the geometry of
      SiNWs. The maximum short circuit current density achieved is 35.6 mA/cm(2). The
      conversion efficiency of solar cell is 9.73% for SiNWs with length, diameter, and
      wire density of ~1.2 MU m, ~75 nm, and 90 MU m(-2), respectively.

PMID- 24574885
TI  - Optimal throughput for cognitive radio with energy harvesting in fading wireless
      channel.
AB  - Energy resource management is a crucial problem of a device with a finite
      capacity battery. In this paper, cognitive radio is considered to be a device
      with an energy harvester that can harvest energy from a non-RF energy resource
      while performing other actions of cognitive radio. Harvested energy will be
      stored in a finite capacity battery. At the start of the time slot of cognitive
      radio, the radio needs to determine if it should remain silent or carry out
      spectrum sensing based on the idle probability of the primary user and the
      remaining energy in order to maximize the throughput of the cognitive radio
      system. In addition, optimal sensing energy and adaptive transmission power
      control are also investigated in this paper to effectively utilize the limited
      energy of cognitive radio. Finding an optimal approach is formulated as a
      partially observable Markov decision process. The simulation results show that
      the proposed optimal decision scheme outperforms the myopic scheme in which
      current throughput is only considered when making a decision. 

PMID- 24574886
TI  - An improved real time image detection system for elephant intrusion along the
      forest border areas.
AB  - Human-elephant conflict is a major problem leading to crop damage, human death
      and injuries caused by elephants, and elephants being killed by humans. In this
      paper, we propose an automated unsupervised elephant image detection system
      (EIDS) as a solution to human-elephant conflict in the context of elephant
      conservation. The elephant's image is captured in the forest border areas and is
      sent to a base station via an RF network. The received image is decomposed using
      Haar wavelet to obtain multilevel wavelet coefficients, with which we perform
      image feature extraction and similarity match between the elephant query image
      and the database image using image vision algorithms. A GSM message is sent to
      the forest officials indicating that an elephant has been detected in the forest
      border and is approaching human habitat. We propose an optimized distance metric
      to improve the image retrieval time from the database. We compare the optimized
      distance metric with the popular Euclidean and Manhattan distance methods. The
      proposed optimized distance metric retrieves more images with lesser retrieval
      time than the other distance metrics which makes the optimized distance method
      more efficient and reliable. 

PMID- 24574887
TI  - Acetic acid bacteria and the production and quality of wine vinegar.
AB  - The production of vinegar depends on an oxidation process that is mainly
      performed by acetic acid bacteria. Despite the different methods of vinegar
      production (more or less designated as either "fast" or "traditional"), the use
      of pure starter cultures remains far from being a reality. Uncontrolled mixed
      cultures are normally used, but this review proposes the use of controlled mixed
      cultures. The acetic acid bacteria species determine the quality of vinegar,
      although the final quality is a combined result of technological process, wood
      contact, and aging. This discussion centers on wine vinegar and evaluates the
      effects of these different processes on its chemical and sensory properties. 

PMID- 24574888
TI  - Detection of earthquake-induced damage in a framed structure using a finite
      element model updating procedure.
AB  - Damage of a 5-story framed structure was identified from two types of measured
      data, which are frequency response functions (FRF) and natural frequencies, using
      a finite element (FE) model updating procedure. In this study, a procedure to
      determine the appropriate weightings for different groups of observations was
      proposed. In addition, a modified frame element which included rotational springs
      was used to construct the FE model for updating to represent concentrated damage
      at the member ends (a formulation for plastic hinges in framed structures
      subjected to strong earthquakes). The results of the model updating and
      subsequent damage detection when the rotational springs (RS model) were used were
      compared with those obtained using the conventional frame elements (FS model).
      Comparisons indicated that the RS model gave more accurate results than the FS
      model. That is, the errors in the natural frequencies of the updated models were
      smaller, and the identified damage showed clearer distinctions between damaged
      and undamaged members and was more consistent with observed damage. 

PMID- 24574889
TI  - Effect of repeated thermal shock on mechanical properties of ZrB2-SiC-BN ceramic
      composites.
AB  - ZrB2-20 vol.% SiC-10 vol.% h-BN (particles) ceramic composites (ZSB) were
      fabricated by hot pressing under inert gas protected. ZSB samples with mean size
      75 * 55 * 40 mm(3) were heated using current heating method and then cooled down
      to low temperature by circulating water. ZSB samples repeatedly went through
      thermal shock with 10-50 times under various conditions, respectively. Diverse
      effects on residual strength of ZSB at different experiment conditions
      (temperatures, thermal shock times, and heating rates) were investigated. The
      test results indicated that the residual strength of specimen materials all
      reached the maximum while the temperature was 1600  degrees C and thermal shock
      number was less than 50 times. Because ZSB samples could not stand the extremely
      serious hyperoxidation at very high temperature (1800  degrees C), the residual
      strength of samples decreased sharply. At 1600  degrees C, when the thermal shock
      times was 20, ZSB samples' residual strength reached the maximum, but it
      decreased to the lowest point while the thermal shock times was 30. So we argued
      that the sensitive thermal shock number was 30. Finally, we analyzed the
      influences on samples residual strength generated by different heating rates at
      the same temperature and thermal shock number; the results showed that when
      heating rate was equal to cooling rate, the residual strength of specimen
      materials reached the maximum.

PMID- 24574891
TI  - Integrated positioning for coal mining machinery in enclosed underground mine
      based on SINS/WSN.
AB  - To realize dynamic positioning of the shearer, a new method based on SINS/WSN is
      studied in this paper. Firstly, the shearer movement model is built and running
      regularity of the shearer in coal mining face has been mastered. Secondly, as
      external calibration of SINS using GPS is infeasible in enclosed underground
      mine, WSN positioning strategy is proposed to eliminate accumulative error
      produced by SINS; then the corresponding coupling model is established. Finally,
      positioning performance is analyzed by simulation and experiment. Results show
      that attitude angle and position of the shearer can be real-timely tracked by
      integrated positioning strategy based on SINS/WSN, and positioning precision meet
      the demand of actual working condition. 

PMID- 24574890
TI  - Derivation and characterization of a ES-like cell line from indian catfish
      Heteropneustes fossilis blastulas.
AB  - A cell line designated as HFB-ES was established from blastula stage embryos of
      H. fossilis (Singhi). The embryonic cells were harvested and maintained in
      Leibovitz's medium supplemented with 15% fetal bovine serum. The cell line had
      been subcultured for more than 90 passages in a period of 24 months. HFB-ES cells
      were able to grow at temperatures between 25 and 35 degrees C with an optimum
      temperature of 28 degrees C. The growth rate of HFB-ES was proportional to FBS
      concentration, with optimum growth seen at 15% FBS concentration. The originality
      of the cell line was confirmed by sequencing of cytochrome oxidase c subunit I
      (COI), cytochrome b gene, and microsatellite DNA profile. Results of chromosome
      complements of HFB showed normal karyo-morphology with 56 (2n) diploid number of
      chromosomes after 40 passages which indicated that the developed cell line is
      chromosomally stable. The pluripotency of HFB was demonstrated by alkaline
      phosphatase activity and Oct-4 gene expression. Expression of GFP reporter gene
      was successful in HFB-ES. These results indicated that HFB-ES could be utilized
      for future gene expression studies. 

PMID- 24574892
TI  - Canaloplasty in open-angle glaucoma surgery: a four-year follow-up.
AB  - Canaloplasty is a new nonperforating surgical technique for open-angle glaucoma,
      in which a microcatheter is inserted within Schlemm's canal for the entire 360
      degrees. A 10-0 prolene suture, which is tied to the distal tip of the
      microcatheter, is then positioned and left tensioned in Schlemm's canal, thus
      facilitating aqueous outflow through natural pathways. A small amount of
      viscoelastic agent is delivered in Schlemm's canal while the catheter is
      withdrawn. The mid-term results are very promising. Based on our cohort of 214
      patients, the percentages of eyes that obtained postoperative IOP <= 21 mmHg, <=
      18 mmHg, and <= 16 mmHg with or without medical therapy after 2 and 3 years were
      88.7%, 73.7%, and 46.2% (2 years); 86.2%, 58.6%, and 37.9% (3 years),
      respectively. The most frequent complications observed included hyphema; descemet
      membrane detachment; IOP spikes; and hypotony. The advantages of canaloplasty
      over trabeculectomy include (1) no subconjunctival bleb; (2) no need for
      antimetabolites; (3) fewer postoperative complications; and (4) a simplified
      follow-up. The disadvantages include the following: (1) a long and rather steep
      surgical learning curve; (2) the need of specific instruments; (3) average
      postoperative IOP levels tend not to be very low; and (4) impossibility to
      perform the entire procedure in some cases.

PMID- 24574893
TI  - A strategy for finding the optimal scale of plant core collection based on Monte
      Carlo simulation.
AB  - Core collection is an ideal resource for genome-wide association studies (GWAS).
      A subcore collection is a subset of a core collection. A strategy was proposed
      for finding the optimal sampling percentage on plant subcore collection based on
      Monte Carlo simulation. A cotton germplasm group of 168 accessions with 20
      quantitative traits was used to construct subcore collections. Mixed linear model
      approach was used to eliminate environment effect and GE (genotype * environment)
      effect. Least distance stepwise sampling (LDSS) method combining 6 commonly used
      genetic distances and unweighted pair-group average (UPGMA) cluster method was
      adopted to construct subcore collections. Homogeneous population assessing method
      was adopted to assess the validity of 7 evaluating parameters of subcore
      collection. Monte Carlo simulation was conducted on the sampling percentage, the
      number of traits, and the evaluating parameters. A new method for "distilling
      free-form natural laws from experimental data" was adopted to find the best
      formula to determine the optimal sampling percentages. The results showed that
      coincidence rate of range (CR) was the most valid evaluating parameter and was
      suitable to serve as a threshold to find the optimal sampling percentage. The
      principal component analysis showed that subcore collections constructed by the
      optimal sampling percentages calculated by present strategy were well
      representative. 

PMID- 24574894
TI  - An investigation into soft error detection efficiency at operating system level.
AB  - Electronic equipment operating in harsh environments such as space is subjected
      to a range of threats. The most important of these is radiation that gives rise
      to permanent and transient errors on microelectronic components. The occurrence
      rate of transient errors is significantly more than permanent errors. The
      transient errors, or soft errors, emerge in two formats: control flow errors
      (CFEs) and data errors. Valuable research results have already appeared in
      literature at hardware and software levels for their alleviation. However, there
      is the basic assumption behind these works that the operating system is reliable
      and the focus is on other system levels. In this paper, we investigate the
      effects of soft errors on the operating system components and compare their
      vulnerability with that of application level components. Results show that soft
      errors in operating system components affect both operating system and
      application level components. Therefore, by providing endurance to operating
      system level components against soft errors, both operating system and
      application level components gain tolerance. 

PMID- 24574895
TI  - Periodic solutions for nonlinear integro-differential systems with piecewise
      constant argument.
AB  - We investigate the existence of the periodic solutions of a nonlinear integro
      differential system with piecewise alternately advanced and retarded argument of
      generalized type, in short DEPCAG; that is, the argument is a general step
      function. We consider the critical case, when associated linear homogeneous
      system admits nontrivial periodic solutions. Criteria of existence of periodic
      solutions of such equations are obtained. In the process we use Green's function
      for periodic solutions and convert the given DEPCAG into an equivalent integral
      equation. Then we construct appropriate mappings and employ Krasnoselskii's fixed
      point theorem to show the existence of a periodic solution of this type of
      nonlinear differential equations. We also use the contraction mapping principle
      to show the existence of a unique periodic solution. Appropriate examples are
      given to show the feasibility of our results. 

PMID- 24574897
TI  - On fractional Model Reference Adaptive Control.
AB  - This paper extends the conventional Model Reference Adaptive Control systems to
      fractional ones based on the theory of fractional calculus. A control law and an
      incommensurate fractional adaptation law are designed for the fractional plant
      and the fractional reference model. The stability and tracking convergence are
      analyzed using the frequency distributed fractional integrator model and Lyapunov
      theory. Moreover, numerical simulations of both linear and nonlinear systems are
      performed to exhibit the viability and effectiveness of the proposed methodology.

PMID- 24574896
TI  - Association of Helicobacter pylori infection with coronary artery disease: is
      Helicobacter pylori a risk factor?
AB  - BACKGROUND: Helicobacter pylori (HP) infection is the most common infection in
      the world and coronary artery disease (CAD) is probably associated with it. The
      aim of this prospective study was to evaluate the association between HP
      infection and CAD in suspected patients referred for coronary angiography. The
      coronary angiography was performed using Judkins method and patients were
      assigned to participate in CAD positive (>50% luminal diameter stenosis) and
      negative groups. The serum HP IgG antibody was checked. RESULTS: Positive and
      negative CAD groups consisted of 62 and 58 patients, respectively. HP was more
      prevalent among CAD+ patients, and with increasing the number of coronary
      arteries with stenosis, the HP seropositivity increased so that 76.3% of patients
      with multiple vessel diseases (MVD) and 70% of patients with single vessel
      diseases (SVD) were HP seropositive versus 50% in control group (P = 0.006).
      Positive CAD was significantly associated with HDL level (P = 0.01) and ESR level
      (P = 0.006). Also, CAD+ patients had higher CRP levels than controls and it was
      statistically different between SVD group and controls (P < 0.05). CONCLUSION: HP
      infection is more prevalent in CAD positive patients and, in case of proving
      causal relationship, it can be considered as a reversible risk factor for CAD.

PMID- 24574898
TI  - Autoimmune complications after hematopoietic stem cell transplantation in
      children with nonmalignant disorders.
AB  - BACKGROUND: Hematopoietic stem cell transplantation (HSCT) remains the only
      curative treatment for many nonmalignant disorders, such as autoimmune disorders,
      inborn metabolic disorders, hemoglobinopathies, and immunodeficiency disorders.
      Autoimmune complications (AICs) after HSCT, such as autoimmune cytopenias,
      autoimmune hepatitis, primary biliary cirrhosis, and autoimmune cutaneous
      manifestations, are still neither well defined nor characterized. PATIENTS:
      Between 2000 and 2012, 92 patients (47 males, 45 females) were treated with HSCT
      in our hospital, 51 with congenital hemoglobinopathies, 19 with primary
      immunodeficiency disease, 10 with metabolic disorders, five with Fanconi anemia,
      three with aplastic anemia, and four with familial hemophagocytic
      lymphohistiocytosis. RESULTS: Mean age at HSCT was 6.4 years (range, 0.2-32
      years) and mean duration of followup after HSCT was 6.81 years (range, 1-11
      years). Sixteen (17.4%) patients developed chronic GVHD and five (5.4%) showed
      sclerodermatous features. Five (5.4%) patients were diagnosed with scleroderma
      manifestations, six (6.5%) with vitiligo, six (6.5%) with autoimmune hemolytic
      anemia (AIHA), six (6.5%) with idiopathic thrombocytopenia, three (3.3%) with
      mild leucopenia, two (2.2%) with aplastic anemia, two (2.2%) (one boy, one girl)
      with autoimmune thyroid disease, and one (1.1%) with autoimmune hepatitis.
      CONCLUSIONS: It was concluded that AICs are clinically significant complications
      after HSCT that contribute to morbidity but not to mortality. AICs are more
      frequent after HSCT for metabolic disorders, and sclerodermatous GVHD is more
      significant in children who underwent allogeneic HSCT for hemoglobinopathies. The
      potential to identify risk factors for AICs could lead to less morbidity and
      mortality and to maintain the patient's quality of life.

PMID- 24574899
TI  - The mediating role of dysfunctional coping in the relationship between beliefs
      about the disease and the level of depression in patients with rheumatoid
      arthritis.
AB  - AIM: Rheumatoid arthritis is one of the most severe chronic diseases. In many
      cases it leads to disability and results in a decreased quality of life and
      increased levels of anxiety and depression. The problem that needs to be
      addressed is the following: which mental processes lead to increased levels of
      depression in patients with rheumatoid arthritis? METHODS: 210 patients with
      rheumatoid arthritis hospitalized in rheumatology wards took part in the
      research. They filled in illness perception questionnaires (IPQ-R) and
      questionnaires for testing strategies of handling stress (Mini-COPE) and the
      level of depression (CES-D). RESULTS: The observed correlation coefficients
      indicate that several elements of the perception of one's disease moderately
      contribute to a high level of depression. Moreover, frequent use of dysfunctional
      coping strategies contributed to high levels of depression. Dysfunctional coping
      was moderately linked to depression. CONCLUSION: The conducted analyses confirmed
      the links between the beliefs about the disease and levels of depression and
      showed that the use of dysfunctional coping strategies mediates the relationship
      between the following elements of the representation of the disease: illness
      coherence, emotional representation, psychological attribution, risk factors, and
      the level of depression.

PMID- 24574900
TI  - Kinetic evidence for near irreversible nonionic micellar entrapment of N-(2'
      Methoxyphenyl)phthalimide (1) under the typical alkaline reaction conditions.
AB  - The values of pseudo-first-order rate constants (k(obs)) for alkaline hydrolysis
      of 1, obtained at 1.0 mM NaOH and within [C(m)E(n)]T (total concentration of
      C(m)E(n)) range of 3.0-5.0 mM for C(12)E(23) and 10-20 mM for C(18)E(20), fail to
      obey pseudophase micellar (PM) model. The values of the fraction of near
      irreversible C m E n micellar trapped 1 molecules (F(IT1)) vary in the range ~0
      0.75 for C(12)E(23) and ~0-0.83 for C(18)E(20) under such conditions. The values
      of F(IT1) become 1.0 at >= 10 mM C(12)E(23) and 50 mM C(18)E(20). Kinetic
      analysis of the observed data at >= 10 mM C(12)E(23) shows near irreversible
      micellar entrapment of 1 molecules under such conditions.

PMID- 24574901
TI  - Single-machine scheduling to minimize total completion time and tardiness with
      two competing agents.
AB  - We consider a single-machine two-agent problem where the objective is to minimize
      a weighted combination of the total completion time and the total tardiness of
      jobs from the first agent given that no tardy jobs are allowed for the second
      agent. A branch-and-bound algorithm is developed to derive the optimal sequence
      and two simulated annealing heuristic algorithms are proposed to search for the
      near-optimal solutions. Computational experiments are also conducted to evaluate
      the proposed branch-and-bound and simulated annealing algorithms. 

PMID- 24574903
TI  - Variational solutions and random dynamical systems to SPDEs perturbed by
      fractional Gaussian noise.
AB  - This paper deals with the following type of stochastic partial differential
      equations (SPDEs) perturbed by an infinite dimensional fractional Brownian motion
      with a suitable volatility coefficient Phi: dX(t) = A(X(t))dt+Phi(t)dB (H) (t),
      where A is a nonlinear operator satisfying some monotonicity conditions. Using
      the variational approach, we prove the existence and uniqueness of variational
      solutions to such system. Moreover, we prove that this variational solution
      generates a random dynamical system. The main results are applied to a general
      type of nonlinear SPDEs and the stochastic generalized p-Laplacian equation. 

PMID- 24574902
TI  - Effectiveness of a single education and counseling intervention in reducing
      anxiety in women undergoing hysterosalpingography: a randomized controlled trial.
AB  - Hysterosalpingography (HSG) is generally considered a stressful and painful
      procedure; we aimed to evaluate whether a single education and counseling
      intervention could reduce women's distress and pain after undergoing HSG for
      infertility. Patients were randomized into control group (n = 108) and
      intervention group (n = 109). All patients filled the following questionnaires
      before and after HSG: Zung self-rating anxiety scale (Z-SAS), Zung self-rating
      depression scale (Z-SDS), and an ad hoc questionnaire designed to evaluate HSG
      procedure knowledge. Pain was scored using a visual analog scale. The
      intervention consisted in a 45-minute individualised session 48 h before HSG. We
      observed a reduction of anxiety and depression scores in the intervention arm
      compared to the control group. After controlling for potential confounding
      variables, intervention was an independent predictor of the difference of Z-SAS
      score before and after HSG. This is the first randomised controlled trial to
      assess the potential effectiveness of a single education and counseling
      intervention to lower anxiety in a diagnostic setting.

PMID- 24574905
TI  - A novel harmony search algorithm based on teaching-learning strategies for 0-1
      knapsack problems.
AB  - To enhance the performance of harmony search (HS) algorithm on solving the
      discrete optimization problems, this paper proposes a novel harmony search
      algorithm based on teaching-learning (HSTL) strategies to solve 0-1 knapsack
      problems. In the HSTL algorithm, firstly, a method is presented to adjust
      dimension dynamically for selected harmony vector in optimization procedure. In
      addition, four strategies (harmony memory consideration, teaching-learning
      strategy, local pitch adjusting, and random mutation) are employed to improve the
      performance of HS algorithm. Another improvement in HSTL method is that the
      dynamic strategies are adopted to change the parameters, which maintains the
      proper balance effectively between global exploration power and local
      exploitation power. Finally, simulation experiments with 13 knapsack problems
      show that the HSTL algorithm can be an efficient alternative for solving 0-1
      knapsack problems. 

PMID- 24574904
TI  - Effect of cytokines on osteoclast formation and bone resorption during mechanical
      force loading of the periodontal membrane.
AB  - Mechanical force loading exerts important effects on the skeleton by controlling
      bone mass and strength. Several in vivo experimental models evaluating the
      effects of mechanical loading on bone metabolism have been reported. Orthodontic
      tooth movement is a useful model for understanding the mechanism of bone
      remodeling induced by mechanical loading. In a mouse model of orthodontic tooth
      movement, TNF-alpha was expressed and osteoclasts appeared on the compressed side
      of the periodontal ligament. In TNF-receptor-deficient mice, there was less tooth
      movement and osteoclast numbers were lower than in wild-type mice. These results
      suggest that osteoclast formation and bone resorption caused by loading forces on
      the periodontal ligament depend on TNF-alpha. Several cytokines are expressed in
      the periodontal ligament during orthodontic tooth movement. Studies have found
      that inflammatory cytokines such as IL-12 and IFN-gamma strongly inhibit
      osteoclast formation and tooth movement. Blocking macrophage colony-stimulating
      factor by using anti-c-Fms antibody also inhibited osteoclast formation and tooth
      movement. In this review we describe and discuss the effect of cytokines in the
      periodontal ligament on osteoclast formation and bone resorption during
      mechanical force loading.

PMID- 24574907
TI  - Closed loop direct adaptive inverse control for linear plants.
AB  - In direct adaptive inverse control (DAIC), parameters of the controller are
      estimated directly in the feed-forward loop. In this paper, we propose a closed
      loop direct adaptive inverse control (CDAIC) scheme which improves tracking,
      error convergence, and disturbance rejection properties of DAIC. CDAIC is
      applicable to stable or stabilized, minimum or nonminimum phase linear plants.
      CDAIC and DAIC are compared using computer simulations for disturbance free and
      disturbed discrete type nonminimum phase linear plants. CDAIC shows better
      results compared to DAIC in terms of mean square tracking error and disturbance
      rejection. 

PMID- 24574908
TI  - Diesel fuel from used frying oil.
AB  - New conversion technologies of used edible oils and waste animal fats into a
      biofuel appropriate for use in standard diesel engines have been developed,
      taking into consideration environmental requirements and improvement in the
      economics of current trans-esterification technologies. The variation in the
      properties of substrates made from used rape oil after treatment with mixed
      adsorbents (active carbon, magnesium silicate) was studied in this work. The
      obtained results are compared with the quality requirements for the substrates
      used in Vogel & Noot GmbH technology for transesterification of oils and fats. 

PMID- 24574906
TI  - Facile and promising method for michael addition of indole and pyrrole to
      electron-deficient trans-beta-nitroolefins catalyzed by a hydrogen bond donor
      catalyst Feist's acid and preliminary study of antimicrobial activity.
AB  - The importance of cooperative hydrogen-bonding effects has been demonstrated
      using novel 3-methylenecyclopropane-1,2-dicarboxylic acid (Feist's acid (FA)) as
      hydrogen bond donor catalysts for the addition of indole and pyrrole to trans
      beta-nitrostyrene derivatives. Because of the hydrogen bond donor (HBD) ability,
      Feist's acid (FA) has been introduced as a new class of hydrogen bond donor
      catalysts for the activation of nitroolefin towards nucleophilic substitution
      reaction. It has effectively catalyzed the Michael addition of indoles and
      pyrrole to beta-nitroolefins under optimum reaction condition to furnish the
      corresponding Michael adducts in good to excellent yields (up to 98%). The method
      is general, atom-economical, convenient, and eco-friendly and could provide
      excellent yields and regioselectivities. Some newly synthesized compounds were
      for examined in vitro antimicrobial activity and their preliminary results are
      reported.

PMID- 24574909
TI  - Four different methods comparison for extraction of astaxanthin from green alga
      Haematococcus pluvialis.
AB  - Haematococcus pluvialis is one of the potent organisms for production of
      astaxanthin. Up to now, no efficient method has been achieved due to its thick
      cell wall hindering solvent extraction of astaxanthin. In this study, four
      different methods, hydrochloric acid pretreatment followed by acetone extraction
      (HCl-ACE), hexane/isopropanol (6:4, v/v) mixture solvents extraction (HEX-IPA),
      methanol extraction followed by acetone extraction (MET-ACE, 2-step extraction),
      and soy-oil extraction, were intensively evaluated for extraction of astaxanthin
      from H. pluvialis. Results showed that HCl-ACE method could obtain the highest
      oil yield (33.3+/-1.1%) and astaxanthin content (19.8+/-1.1%). Quantitative NMR
      analysis provided the fatty acid chain profiles of total lipid extracts. In all
      cases, oleyl chains were predominant, and high amounts of polyunsaturated fatty
      acid chains were observed and the major fatty acid components were oleic acid (13
      35%), linoleic acid (37-43%), linolenic acid (20-31%), and total saturated acid
      (17-28%). DPPH radical scavenging activity of extract obtained by HCl-ACE was
      73.2+/-1.0%, which is the highest amongst the four methods. The reducing power of
      extract obtained by four extraction methods was also examined. It was concluded
      that the proposed extraction method of HCl-ACE in this work allowed efficient
      astaxanthin extractability with high antioxidant properties.

PMID- 24574910
TI  - Adaptive neural network motion control of manipulators with experimental
      evaluations.
AB  - A nonlinear proportional-derivative controller plus adaptive neuronal network
      compensation is proposed. With the aim of estimating the desired torque, a two
      layer neural network is used. Then, adaptation laws for the neural network
      weights are derived. Asymptotic convergence of the position and velocity tracking
      errors is proven, while the neural network weights are shown to be uniformly
      bounded. The proposed scheme has been experimentally validated in real time.
      These experimental evaluations were carried in two different mechanical systems:
      a horizontal two degrees-of-freedom robot and a vertical one degree-of-freedom
      arm which is affected by the gravitational force. In each one of the two
      experimental set-ups, the proposed scheme was implemented without and with
      adaptive neural network compensation. Experimental results confirmed the tracking
      accuracy of the proposed adaptive neural network-based controller. 

PMID- 24574912
TI  - MRI and PET image fusion using fuzzy logic and image local features.
AB  - An image fusion technique for magnetic resonance imaging (MRI) and positron
      emission tomography (PET) using local features and fuzzy logic is presented. The
      aim of proposed technique is to maximally combine useful information present in
      MRI and PET images. Image local features are extracted and combined with fuzzy
      logic to compute weights for each pixel. Simulation results show that the
      proposed scheme produces significantly better results compared to state-of-art
      schemes. 

PMID- 24574911
TI  - Effect of micro- and nanomagnetite on printing toner properties.
AB  - Toner is a main component of electrophotographic printing and copying processes.
      One of the most important ingredients of toner is magnetite (Fe3O4) which
      provides the tribocharging property for toner particles. In this study, nano- and
      microparticles of Fe3O4 were synthesized using the coprecipitation method and
      different amounts of lauric acid as a surfactant. The synthesized nano and micro
      Fe3O4 was then used as the charge control agent to produce toner by emulsion
      aggregation. The Fe3O4 and toner were characterized by X-ray powder diffraction
      (XRD), atomic gradient force magnetometry (AGFM), dynamic laser scattering (DLS),
      particle size analysis, differential scanning calorimetry (DSC), and scanning
      electron microscopy (SEM). The results show that the optimum amount of surfactant
      not only reduced particle size but also reduced the magnetite properties of
      Fe3O4. It was found that the magnetite behavior of the toner is not similar to
      the Fe3O4 used to produce it. Although small-sized Fe3O4 created toner with a
      smaller size, toners made with micro Fe3O4 showed better magnetite properties
      than toner made with nano Fe3O4. 

PMID- 24574913
TI  - High-speed current dq PI controller for vector controlled PMSM drive.
AB  - High-speed current controller for vector controlled permanent magnet synchronous
      motor (PMSM) is presented. The controller is developed based on modular design
      for faster calculation and uses fixed-point proportional-integral (PI) method for
      improved accuracy. Current dq controller is usually implemented in digital signal
      processor (DSP) based computer. However, DSP based solutions are reaching their
      physical limits, which are few microseconds. Besides, digital solutions suffer
      from high implementation cost. In this research, the overall controller is
      realizing in field programmable gate array (FPGA). FPGA implementation of the
      overall controlling algorithm will certainly trim down the execution time
      significantly to guarantee the steadiness of the motor. Agilent 16821A Logic
      Analyzer is employed to validate the result of the implemented design in FPGA.
      Experimental results indicate that the proposed current dq PI controller needs
      only 50 ns of execution time in 40 MHz clock, which is the lowest computational
      cycle for the era. 

PMID- 24574914
TI  - A loop-mediated isothermal amplification assay for rapid detection of cyprinid
      herpesvirus 2 in gibel carp (Carassius auratus gibelio).
AB  - A rapid and sensitive loop-mediated isothermal amplification (LAMP) assay for
      Cyprinid herpesvirus 2 (CyHV-2) detection in gibel carp was developed. Following
      cloning and sequencing of the putative DNA helicase gene of CyHV-2 isolate from
      China, a set of four specific primers was designed based on the sequence. The
      MgCl2 concentration and the reaction temperature were optimized to 6 mM, 64
      degrees C, respectively. LAMP products were detected by visual inspection of a
      color change due to addition of SYBR Green I stain. The specificity and
      sensitivity of the LAMP assay were determined. No cross-reaction was observed
      with other fish DNA viruses including eel herpesvirus, koi herpesvirus, and
      Chinese giant salamander iridovirus. The LAMP assay was found to be equally
      sensitive as nested PCR. A comparative evaluation of 10 fish samples using LAMP
      and nested PCR assays showed an overall correlation in positive and negative
      results for CyHV-2. These results indicate that the LAMP assay is simple,
      sensitive, and specific and has a great potential use for CyHV-2 detection in the
      laboratory and field. 

PMID- 24574915
TI  - Design, synthesis, characterization, and computational studies on benzamide
      substituted Mannich bases as novel, potential antibacterial agents.
AB  - A series of benzamide substituted Mannich bases (1-7) were synthesized. The
      synthesized derivatives were authenticated by TLC, UV-Visible, FTIR, NMR, and
      mass spectroscopic techniques and further screened for in vitro antibacterial
      activity by test tube dilution method using amoxicillin and cefixime as standard
      drugs. The compounds 5, 6, and 7 were found to be the most active antibacterial
      agents among all the synthesized compounds. The physicochemical similarity of the
      compounds with standard drugs was assessed by calculating various physicochemical
      properties using software programs. The percent similarity of synthesized
      compounds was found to be good and compound 1 was found to have higher percentage
      of similarity. The compounds were subjected to QSAR by multilinear regression
      using Analyze it version 3.0 software, and four statistically sound models were
      developed with R2 (0.963-0.997), Radj2 (0.529-0.982), and Q2 (0.998-0.999) with
      good F (2.35-65.56) values.

PMID- 24574916
TI  - Analysis of the influence of quantile regression model on mainland tourists'
      service satisfaction performance.
AB  - It is estimated that mainland Chinese tourists travelling to Taiwan can bring
      annual revenues of 400 billion NTD to the Taiwan economy. Thus, how the Taiwanese
      Government formulates relevant measures to satisfy both sides is the focus of
      most concern. Taiwan must improve the facilities and service quality of its
      tourism industry so as to attract more mainland tourists. This paper conducted a
      questionnaire survey of mainland tourists and used grey relational analysis in
      grey mathematics to analyze the satisfaction performance of all satisfaction
      question items. The first eight satisfaction items were used as independent
      variables, and the overall satisfaction performance was used as a dependent
      variable for quantile regression model analysis to discuss the relationship
      between the dependent variable under different quantiles and independent
      variables. Finally, this study further discussed the predictive accuracy of the
      least mean regression model and each quantile regression model, as a reference
      for research personnel. The analysis results showed that other variables could
      also affect the overall satisfaction performance of mainland tourists, in
      addition to occupation and age. The overall predictive accuracy of quantile
      regression model Q0.25 was higher than that of the other three models. 

PMID- 24574918
TI  - Estimating the occurrence of wind-driven coastal upwelling associated with
      "Aoshio" on the northeast shore of Tokyo Bay, Japan: an analytical model.
AB  - "Aoshio" in Tokyo Bay is a hydroenvironmental phenomenon in which seawater
      appears milky blue due to reflection of sunshine off surface water which contains
      lots of sulfur particles. Its appearance is due to coastal upwelling of bottom
      oxygen-depleted water, which causes many deaths of shellfish and other aquatic
      animals around the bay. In this study, we derived some analytical solutions in
      the context of a two-layered fluid and used them to make a simple analytical
      model to estimate the occurrence of "Aoshio" phenomenon on the northeast shore of
      Tokyo Bay. Comparison with observation data suggested that this model was valid
      to a certain degree. 

PMID- 24574917
TI  - The role of plant cell wall proteins in response to salt stress.
AB  - Contemporary agriculture is facing new challenges with the increasing population
      and demand for food on Earth and the decrease in crop productivity due to abiotic
      stresses such as water deficit, high salinity, and extreme fluctuations of
      temperatures. The knowledge of plant stress responses, though widely extended in
      recent years, is still unable to provide efficient strategies for improvement of
      agriculture. The focus of study has been shifted to the plant cell wall as a
      dynamic and crucial component of the plant cell that could immediately respond to
      changes in the environment. The investigation of plant cell wall proteins,
      especially in commercially important monocot crops revealed the high involvement
      of this compartment in plants stress responses, but there is still much more to
      be comprehended. The aim of this review is to summarize the available data on
      this issue and to point out the future areas of interest that should be studied
      in detail. 

PMID- 24574919
TI  - Quantitative analysis and fingerprint profiles for quality control of Fructus
      Schisandrae by gas chromatography: mass spectrometry.
AB  - This paper describes a simple, rapid, and effective quality assessment method for
      Fructus Schisandrae by gas chromatography-mass spectrum (GC-MS). The method was
      established by using specific lignan fingerprint profiles and quantitation of
      characteristic compounds in this herbal medicine. The GC-MS fingerprints of 15
      batches of Schisandra samples from different regions of China showed similar
      lignan profiles. Five peaks were selected as characteristic peaks, and all of
      these were identified by using GC-MS techniques. The relative retention times of
      these characteristic peaks in the GC-MS fingerprint were established as an
      important parameter for identification of Schisandra samples. Meanwhile, relative
      peak areas may be a feasible approach to discriminate the S. chinensis and S.
      sphenanthera. Finally, these pharmacologically active constituents in the titled
      plant, schisandrins A-C and schizandrols A and B, were quantitatively determined
      using a validated GC-MS method. 

PMID- 24574920
TI  - The complex action recognition via the correlated topic model.
AB  - Human complex action recognition is an important research area of the action
      recognition. Among various obstacles to human complex action recognition, one of
      the most challenging is to deal with self-occlusion, where one body part occludes
      another one. This paper presents a new method of human complex action
      recognition, which is based on optical flow and correlated topic model (CTM).
      Firstly, the Markov random field was used to represent the occlusion relationship
      between human body parts in terms of an occlusion state variable. Secondly, the
      structure from motion (SFM) is used for reconstructing the missing data of point
      trajectories. Then, we can extract the key frame based on motion feature from
      optical flow and the ratios of the width and height are extracted by the human
      silhouette. Finally, we use the topic model of correlated topic model (CTM) to
      classify action. Experiments were performed on the KTH, Weizmann, and UIUC action
      dataset to test and evaluate the proposed method. The compared experiment results
      showed that the proposed method was more effective than compared methods. 

PMID- 24574921
TI  - Dynamic calibration and validation of an accelerometer force balance for
      hypersonic lifting models.
AB  - An accelerometer-based force balance was designed and developed for the
      measurement of drag, lift, and rolling moment on a blunt-nosed, flapped delta
      wing in a short-duration hypersonic shock tunnel. Calibration and validation of
      the balance were carried out by a convolution technique using hammer pulse test
      and surface pressure measurements. In the hammer pulse test, a known impulse was
      applied to the model in the appropriate direction using an impulse hammer, and
      the corresponding output of the balance (acceleration) was recorded. Fast Fourier
      Transform (FFT) was operated on the output of the balance to generate a system
      response function, relating the signal output to the corresponding load input.
      Impulse response functions for three components of the balance, namely, axial,
      normal, and angular, were obtained for a range of input load. The angular system
      response function was corresponding to rolling of the model. The impulse response
      functions thus obtained, through dynamic calibration, were operated on the output
      (signals) of the balance under hypersonic aerodynamic loading conditions in the
      tunnel to get the time history of the unknown aerodynamic forces and moments
      acting on the model. Surface pressure measurements were carried out on the model
      using high frequency pressure transducers, and forces and moments were deduced
      thereon. Tests were carried out at model angles of incidence of 0, 5, 10, and 15
      degrees. A good agreement was observed among the results of different
      experimental methods. The balance developed is a comprehensive force/moment
      measurement device that can be used on complex, lifting, aerodynamic geometries
      in ground-based hypersonic test facilities. 

PMID- 24574922
TI  - Fault tolerant coverage and connectivity in presence of channel randomness.
AB  - Some applications of wireless sensor network require K-coverage and K
      connectivity to ensure the system to be fault tolerance and to make it more
      reliable. Therefore, it makes coverage and connectivity an important issue in
      wireless sensor networks. In this paper, we proposed K-coverage and K
      connectivity models for wireless sensor networks. In both models, nodes are
      distributed according to Poisson distribution in the sensor field. To make the
      proposed model more realistic we used log-normal shadowing path loss model to
      capture the radio irregularities and studied its impact on K-coverage and K
      connectivity. The value of K can be different for different types of
      applications. Further, we also analyzed the problem of node failure for K
      coverage model. In the simulation section, results clearly show that coverage and
      connectivity of wireless sensor network depend on the node density, shadowing
      parameters like the path loss exponent, and standard deviation. 

PMID- 24574923
TI  - The connection between the toxicity of anthracyclines and their ability to
      modulate the P-glycoprotein-mediated transport in A549, HepG2, and MCF-7 cells.
AB  - Multidrug resistance (MDR) is a major obstacle to the successful chemotherapy of
      solid tumors. We compared the resistance of the most popular solid tumors, breast
      adenocarcinoma (MCF-7 cell line) and nonsmall cell lung (A549 cell line)
      hepatocellular liver carcinoma (HepG2 cells), to aclarubicin (ACL) and
      doxorubicin (DOX). This research aimed at determining the relation between the
      toxicity of ACL and DOX, their cell accumulation, and then effect on P
      glycoprotein functionality. ACL is more cytotoxic for tumor cells compared to
      DOX. The intracellular concentration of drugs in cancer cells was dependent on
      the dose of the drugs and the time of incubation. The P-gp inhibitor Verapamil
      (V) increased DOX accumulation in all tested cell lines. By contrast, the
      intracellular level of ACL was not affected by this modifying agent. The
      assessment of the uptake of 5,5',6,6'-tetrachloro-1,1',3,3'
      tetraethylbenzimidazolocarbocyanine iodide (JC-1) or Rhodamine 123 (R123) allows
      the evaluation of the different influence of drugs on P-gp activity which is in
      agreement with the estimation of expression measured by MDR-1 shift assay. These
      data suggest that ACL is less P-gp dependent than DOX and consequently may be
      used in a clinical setting to increase treatment efficacy in resistant human
      tumors. 

PMID- 24574924
TI  - The evolving concepts of cancer stem cells in head and neck squamous cell
      carcinoma.
AB  - There is increasing evidence that the growth and spread of cancers is driven by a
      small subpopulation of cancer stem cells (CSCs)--the only cells that are capable
      of long-term self-renewal and generation of the phenotypically diverse tumor cell
      population. CSCs have been identified and isolated in a variety of human cancers
      including head and neck squamous cell carcinoma (HNSCC). The concept of cancer
      stem cells may have profound implications for our understanding of tumor biology
      and for the design of novel treatments targeted toward these cells. The present
      review is an attempt to conceptualize the role of CSCs in HNSCC--its implication
      in tumorigenesis and the possible additional approach in current treatment
      strategies.

PMID- 24574925
TI  - Community structure and succession regulation of fungal consortia in the
      lignocellulose-degrading process on natural biomass.
AB  - The study aims to investigate fungal community structures and dynamic changes in
      forest soil lignocellulose-degrading process. rRNA gene clone libraries for the
      samples collected in different stages of lignocellulose degradation process were
      constructed and analyzed. A total of 26 representative RFLP types were obtained
      from original soil clone library, including Mucoromycotina (29.5%), unclassified
      Zygomycetes (33.5%), Ascomycota (32.4%), and Basidiomycota (4.6%). When soil
      accumulated with natural lignocellulose, 16 RFLP types were identified from 8-day
      clone library, including Basidiomycota (62.5%), Ascomycota (36.1%), and Fungi
      incertae sedis (1.4%). After enrichment for 15 days, identified 11 RFLP types
      were placed in 3 fungal groups: Basidiomycota (86.9%), Ascomycota (11.5%), and
      Fungi incertae sedis (1.6%). The results showed richer, more diversity and
      abundance fungal groups in original forest soil. With the degradation of
      lignocellulose, fungal groups Mucoromycotina and Ascomycota decreased gradually,
      and wood-rotting fungi Basidiomycota increased and replaced the opportunist fungi
      to become predominant group. Most of the fungal clones identified in sample were
      related to the reported lignocellulose-decomposing strains. Understanding of the
      microbial community structure and dynamic change during natural lignocellulose
      degrading process will provide us with an idea and a basis to construct available
      commercial lignocellulosic enzymes or microbial complex. 

PMID- 24574928
TI  - Low-complexity user selection for rate maximization in MIMO broadcast channels
      with downlink beamforming.
AB  - We present in this work a low-complexity algorithm to solve the sum rate
      maximization problem in multiuser MIMO broadcast channels with downlink
      beamforming. Our approach decouples the user selection problem from the resource
      allocation problem and its main goal is to create a set of quasiorthogonal users.
      The proposed algorithm exploits physical metrics of the wireless channels that
      can be easily computed in such a way that a null space projection power can be
      approximated efficiently. Based on the derived metrics we present a mathematical
      model that describes the dynamics of the user selection process which renders the
      user selection problem into an integer linear program. Numerical results show
      that our approach is highly efficient to form groups of quasiorthogonal users
      when compared to previously proposed algorithms in the literature. Our user
      selection algorithm achieves a large portion of the optimum user selection sum
      rate (90%) for a moderate number of active users. 

PMID- 24574926
TI  - Interaction between DNA and trimethyl-ammonium bromides with different alkyl
      chain lengths.
AB  - The interaction between lambda--DNA and cationic surfactants with varying alkyl
      chain lengths was investigated. By dynamic light scattering method, the trimethyl
      ammonium bromides-DNA complex formation was shown to be dependent on the length
      of the surfactant's alkyl chain. For surfactants with sufficient long alkyl chain
      (CTAB, TTAB, DTAB), the compacted particles exist with a size of ~60-110 nm at
      low surfactant concentrations. In contrast, high concentration of surfactants
      leads to aggregates with increased sizes. Atomic force microscope scanning also
      supports the above observation. Zeta potential measurements show that the
      potential of the particles decreases with the increase of surfactant
      concentration (CTAB, TTAB, DTAB), which contributes much to the coagulation of
      the particles. For OTAB, the surfactant with the shortest chain in this study, it
      cannot fully neutralize the charges of DNA molecules; consequently, the complex
      is looser than other surfactant-DNA structures.

PMID- 24574927
TI  - Effect of fluticasone and salmeterol on tracheal responsiveness to ovalbumin and
      lung inflammation, administrated during and after sensitization.
AB  - The effect of duration of administration of fluticasone propionate and salmeterol
      on tracheal responsiveness to ovalbumin and total and differential white blood
      cell in sensitized guinea pig was examined. Six groups of guinea pigs (n=7) were
      sensitized to ovalbumin. Three groups of them were subjected to inhaled
      fluticasone propionate and salmeterol, one group during sensitization (A), one
      group after that (for 18 days, B), and the other one during sensitization but
      with 18 days delay before measurements (C). Three other groups were treated with
      placebo in the same manner. The tracheal responsiveness to ovalbumin and total
      and differential white blood cells of three placebo groups were significantly
      higher than those of control group (P<0.001 for all cases). Tracheal
      responsiveness to ovalbumin and total and differential white blood cell in
      treated groups with fluticasone propionate and salmeterol were significantly
      decreased compared to those of placebo groups (nonsignificant to P<0.001). The
      improvement in all variables in treatment groups A and C were more pronounced
      than group B. The results showed that fluticasone propionate and salmeterol had a
      prevention effect on tracheal hyperresponsiveness to ovalbumin and lung
      inflammation which was more pronounced when administered during than after
      sensitization.

PMID- 24574929
TI  - Reentry trajectory optimization based on a multistage pseudospectral method.
AB  - Of the many direct numerical methods, the pseudospectral method serves as an
      effective tool to solve the reentry trajectory optimization for hypersonic
      vehicles. However, the traditional pseudospectral method is time-consuming due to
      large number of discretization points. For the purpose of autonomous and adaptive
      reentry guidance, the research herein presents a multistage trajectory control
      strategy based on the pseudospectral method, capable of dealing with the
      unexpected situations in reentry flight. The strategy typically includes two
      subproblems: the trajectory estimation and trajectory refining. In each
      processing stage, the proposed method generates a specified range of trajectory
      with the transition of the flight state. The full glide trajectory consists of
      several optimal trajectory sequences. The newly focused geographic constraints in
      actual flight are discussed thereafter. Numerical examples of free-space flight,
      target transition flight, and threat avoidance flight are used to show the
      feasible application of multistage pseudospectral method in reentry trajectory
      optimization. 

PMID- 24574930
TI  - Facebook enhances antidepressant pharmacotherapy effects.
AB  - Treatment-resistant major depressive disorder (TR-MDD) is a complex condition,
      with very low remission rates. In recent years some studies have been conducted
      on the implementation of cognitive behavioral therapy and psychodynamic
      psychotherapy interventions via the Internet to MDD patients, and results have
      been promising. However, there have been no studies in patients with TR-MDD nor
      with the use of Facebook with the psychiatrist as "friend." 60 TR-MDD patients
      were randomized to one of three groups: Facebook group with psychiatrist as
      "friend," Facebook group without psychiatrist as "friend," and control group (no
      Facebook use). Both Facebook groups spent at least 1 hour/day on Facebook, 7
      days/week, during the 3 months. All patients maintained their usual
      pharmacotherapy. All participants were evaluated at baseline and at 1, 2, and 3
      months for depressive symptoms using HAD17 and BDI-II. Results show that both
      Facebook groups had a decrease on HADM17 and BDI-II scores as well as higher
      remission and response rates than the control group, with better results if the
      psychiatrist was a "friend" on Facebook. Therefore, in TR-MDD, Facebook can be
      used as an effective enhancement therapy, adjuvant to pharmacological therapy
      with regular consultations, especially if the psychiatrist is the patient's
      online "friend." 

PMID- 24574931
TI  - Using the high-level based program interface to facilitate the large scale
      scientific computing.
AB  - This paper is to make further research on facilitating the large-scale scientific
      computing on the grid and the desktop grid platform. The related issues include
      the programming method, the overhead of the high-level program interface based
      middleware, and the data anticipate migration. The block based Gauss Jordan
      algorithm as a real example of large-scale scientific computing is used to
      evaluate those issues presented above. The results show that the high-level based
      program interface makes the complex scientific applications on large-scale
      scientific platform easier, though a little overhead is unavoidable. Also, the
      data anticipation migration mechanism can improve the efficiency of the platform
      which needs to process big data based scientific applications. 

PMID- 24574932
TI  - Development of p-y curves of laterally loaded piles in cohesionless soil.
AB  - The research on damages of structures that are supported by deep foundations has
      been quite intensive in the past decade. Kinematic interaction in soil-pile
      interaction is evaluated based on the p-y curve approach. Existing p-y curves
      have considered the effects of relative density on soil-pile interaction in sandy
      soil. The roughness influence of the surface wall pile on p-y curves has not been
      emphasized sufficiently. The presented study was performed to develop a series of
      p-y curves for single piles through comprehensive experimental investigations.
      Modification factors were studied, namely, the effects of relative density and
      roughness of the wall surface of pile. The model tests were subjected to lateral
      load in Johor Bahru sand. The new p-y curves were evaluated based on the
      experimental data and were compared to the existing p-y curves. The soil-pile
      reaction for various relative density (from 30% to 75%) was increased in the
      range of 40-95% for a smooth pile at a small displacement and 90% at a large
      displacement. For rough pile, the ratio of dense to loose relative density soil
      pile reaction was from 2.0 to 3.0 at a small to large displacement. Direct
      comparison of the developed p-y curve shows significant differences in the
      magnitude and shapes with the existing load-transfer curves. Good comparison with
      the experimental and design studies demonstrates the multidisciplinary
      applications of the present method. 

PMID- 24574933
TI  - Knowledge discovery from vibration measurements.
AB  - The framework as well as the particular algorithms of pattern recognition process
      is widely adopted in structural health monitoring (SHM). However, as a part of
      the overall process of knowledge discovery from data bases (KDD), the results of
      pattern recognition are only changes and patterns of changes of data features. In
      this paper, based on the similarity between KDD and SHM and considering the
      particularity of SHM problems, a four-step framework of SHM is proposed which
      extends the final goal of SHM from detecting damages to extracting knowledge to
      facilitate decision making. The purposes and proper methods of each step of this
      framework are discussed. To demonstrate the proposed SHM framework, a specific
      SHM method which is composed by the second order structural parameter
      identification, statistical control chart analysis, and system reliability
      analysis is then presented. To examine the performance of this SHM method, real
      sensor data measured from a lab size steel bridge model structure are used. The
      developed four-step framework of SHM has the potential to clarify the process of
      SHM to facilitate the further development of SHM techniques. 

PMID- 24574934
TI  - Measurement of voice onset time in maxillectomy patients.
AB  - Objective speech evaluation using acoustic measurement is needed for the proper
      rehabilitation of maxillectomy patients. For digital evaluation of consonants,
      measurement of voice onset time is one option. However, voice onset time has not
      been measured in maxillectomy patients as their consonant sound spectra exhibit
      unique characteristics that make the measurement of voice onset time challenging.
      In this study, we established criteria for measuring voice onset time in
      maxillectomy patients for objective speech evaluation. We examined voice onset
      time for /ka/ and /ta/ in 13 maxillectomy patients by calculating the number of
      valid measurements of voice onset time out of three trials for each syllable.
      Wilcoxon's signed rank test showed that voice onset time measurements were more
      successful for /ka/ and /ta/ when a prosthesis was used (Z = -2.232, P = 0.026
      and Z = -2.401, P = 0.016, resp.) than when a prosthesis was not used. These
      results indicate a prosthesis affected voice onset measurement in these patients.
      Although more research in this area is needed, measurement of voice onset time
      has the potential to be used to evaluate consonant production in maxillectomy
      patients wearing a prosthesis. 

PMID- 24574935
TI  - Mental health of adults treated in adolescence with scoliosis-specific exercise
      program or observed for idiopathic scoliosis.
AB  - OBJECTIVE: To examine general mental health in adult males and females, who in
      adolescence participated in a scoliosis-specific therapeutic exercise program or
      were under observation due to diagnosis of scoliosis. DESIGN: Registry-based,
      cross-sectional study with retrospective data collection. METHODS: Sixty-eight
      subjects (43 women) aged 30.10 (25-39) years, with mild or moderate scoliosis (11
      36 degrees  Cobb angle), and 76 (38 women) nonscoliotic subjects, aged 30.11 (24
      38) years, participated. The time period since the end of the exercise or
      observation regimes was 16.5 (12-26) years. Beck Depression Inventory (BDI) and
      General Health Questionnaire (GHQ-28) scores were analyzed with the chi(2) and U
      tests. Multiple regression analyses for confounders were also performed. RESULTS:
      Intergroup differences of demographic characteristics were nonsignificant.
      Scoliosis, gender, participation in the exercise program, employment, and marital
      status were associated with BDI scores. The presence of scoliosis and
      participation in the exercise program manifested association with the symptoms.
      Higher GHQ-28 "somatic symptoms" subscale scores interacted with the education
      level. CONCLUSIONS: Our findings correspond to the reports of a negative impact
      of the diagnosis of scoliosis and treatment on mental health. The decision to
      introduce a therapeutic program in children with mild deformities should be made
      with judgment of potential benefits, risks, and harm.

PMID- 24574937
TI  - Structural characterisation and mechanical FE analysis of conventional and M-Wire
      Ni-Ti alloys used in endodontic rotary instruments.
AB  - The purpose of this study is to understand how the M-Wire alloy conditions the
      mechanical flexibility of endodontic rotary files at body temperature.Two
      different rotary instruments, a Profile GT 20/.06 and a Profile GT Series X
      20/.06, were selected due to their geometrical similarity and their different
      constituent alloy. GT series X files are made from M-Wire, a Ni-Ti alloy
      allegedly having higher flexibility at body temperature. Both files were analysed
      by X-Ray Diffraction and Differential Scanning Calorimetry to investigate phase
      transformations and the effects of working temperature on these different alloys.
      Mechanical behaviour was assessed by means of static bending and torsional Finite
      Element simulations, taking into account the nonlinear superelastic behaviour of
      Ni-Ti materials. It was found that GT files present austenitic phase at body
      temperature, whereas GT series X present R-phase at temperatures under 40 
      degrees C with a potential for larger flexibility. For the same load conditions,
      simulations showed that the slight geometrical differences between the two files
      do not introduce great disagreement in the instruments' mechanical response. It
      was confirmed that M-Wire increases the instrument's flexibility, mainly due to
      the presence of R-phase at body temperature.

PMID- 24574936
TI  - The P2X7 receptor: a key player in immune-mediated bone loss?
AB  - Inflammatory diseases are often multiorganic diseases with manifestations not
      related directly to the primary affected organ. They are often complicated by a
      generalized bone loss that subsequently leads to osteoporosis and bone fractures.
      The exact mechanism for the accompanying bone loss is not understood in full
      detail, but factors such as glucocorticoid treatment, immobilization,
      malnutrition, and insufficient intake of vitamin D play a role. However, it has
      become evident that the inflammatory process itself is involved and the resulting
      bone loss is termed immune-mediated bone loss. It stems from an increase in bone
      resorption and the pro-inflammatory cytokines tumor necrosis factor alpha and
      interleukin 1 beta and has been shown to not only mediate the inflammatory
      response but also to strongly stimulate bone degradation. The purinergic P2X7
      receptor is central in the processing of these two cytokines and in the
      initiation of the inflammatory response, and it is a key molecule in the
      regulation of both bone formation and bone resorption. The aim of this review is
      therefore to provide evidence-based novel hypotheses of the role of ATP-mediated
      purinergic signalling via the P2X7 receptor in immune-mediated bone loss and 
      osteoporosis. 

PMID- 24574938
TI  - Effect of GABAB receptor antagonist (CGP35348) on learning and memory in albino
      mice.
AB  - The present study was designed to demonstrate the potential effect of CGP 35348
      (GABAB receptor antagonist) on the learning, memory formation, and neuromuscular
      coordination in albino mouse. Mice were intrapertoneally injected with 1 mg CGP
      35348/mL of distilled water/Kg body weight, while the control animals were
      injected with equal volume of saline solution. A battery of neurological tests
      was applied following the intrapertoneal injections. Results of rota rod
      indicated that CGP 35348 had no effect on neuromuscular coordination in both male
      (P=0.528) and female (P=0.125) albino mice. CGP 35348 treated females
      demonstrated poor exploratory behavior during open filed for several parameters
      (time mobile (P=0.04), time immobile (P=0.04), rotations (P=0.04), and
      anticlockwise rotations (P=0.038)). The results for Morris water maze (MWM)
      retention phase indicated that CGP 35348 treated male mice took shorter latency
      to reach the hidden platform (P=0.04) than control indicating improved memory.
      This observation was complemented by the swim strategies used by mice during
      training days in MWM as CGP 35348 treated males used more direct and focal
      approach to reach the platform as the training proceeded.

PMID- 24574939
TI  - The comparison of double J stent insertion and conservative treatment alone in
      severe pure gestational hydronephrosis: a case controlled clinical study.
AB  - OBJECTIVE: Management options of gestational hydronephrosis are based on the
      coexisting stone disease, pyelonephritis, and renal disease. However, the
      management option and its consequences in the absence of a coexisting disease
      state are not clear. In this study we aimed to compare the effectiveness of
      conservative treatment and double J insertion in symptomatic pure gestational
      hydronephrosis. MATERIAL AND METHODS: The data of the women with severe pure
      gestational hydronephrosis over a nine-year period was collected retrospectively.
      The included women were grouped into two according to receiving double J stent
      insertion or conservative treatments. RESULTS: Double J insertion and
      conservative treatment groups included 24 and 29 women, respectively.
      Hydronephrosis was demonstrated on the right, left, or both kidneys in 37 (70%),
      13 (24%), and 3 (6%) women, respectively. None of the participants gave birth
      prior to the 37th week. The demographics, initial pain scores, the severity of
      the hydronephrosis during first admission, and pain scores one week after the
      interventions did not differ significantly between groups (P > 0.05). Similarly,
      the rates of complications, postpartum pain scores, and permanent hydronephrosis
      did not differ between groups (P > 0.05). CONCLUSION: Double J insertion in
      symptomatic pure gestational hydronephrosis adds no benefit to conservative
      treatment.

PMID- 24574940
TI  - Illness and determinants of health-related quality of life in a cross-sectional
      sample of schoolchildren in different weight categories.
AB  - AIM: To study associations between health-related quality of life (HRQoL),
      frequency of illness, and weight in primary school children in southern Germany.
      METHODS: Data from baseline measurements of the outcome evaluation of a teacher
      based health promotion programme ("Join the Healthy Boat") were analysed. Parents
      provided information about their children's HRQoL (KINDL(R), EQ5D-Y Visual
      Analogue Scale). The number of visits to a physician, children's days of absence
      because of sickness, and parental days of absence from work due to their
      children's illness during the last year of school/kindergarten were queried.
      Children's weight status was determined by body mass index (BMI), central obesity
      by waist to height ratio (WHtR >=0.5). RESULTS: From 1,888 children (7.1+/-0.6
      years), 7.8% were underweight, 82% had normal weight, 5.7% were overweight and
      4.4% obese. 8.4% of all children were centrally obese. Bivariate analysis showed
      no significant differences for parental absence and visits to a physician in
      weight groups classified by BMI, but obese children had more sick days than non
      obese. Centrally obese children differed significantly from the rest in the
      number of sick days and visits to a physician, but not in the frequency of
      parental absence. In regression analyses, central obesity correlated
      significantly with EQ5D-Y VAS, KINDL(R) total score and the subscales of
      "psyche", "family" and "friends". BMI weight groups showed no significant
      associations. CONCLUSIONS: Central obesity but not BMI derived overweight and
      obesity is associated with HRQoL and visits to a physician in primary school
      children. Future studies should include WHtR. Preventive measures for children
      should focus on a reduction of or slowed increase in waist circumference.

PMID- 24574942
TI  - Gastrointestinal Obstruction due to Solitary Lymph Node Recurrence of Alpha
      Fetoprotein-Producing Gastric Carcinoma with Enteroblastic Differentiation.
AB  - We report an unusual case of alpha-fetoprotein (AFP)-producing gastric carcinoma
      with enteroblastic differentiation. A 75-year-old woman was admitted to our
      hospital with occasional upper abdominal discomfort. We performed gastroscopy and
      observed a type 2 tumor, primarily in the pyloric region. Histological
      examination of biopsies confirmed gastric adenocarcinoma. Based on these
      findings, we diagnosed gastric adenocarcinoma and performed laparoscopic distal
      gastrectomy with lymph node dissection. Histological examination revealed an
      invasive lesion composed of adenocarcinoma with a tubulopapillary growth pattern.
      Tumor cells were cuboidal in shape with characteristically clear cytoplasm rich
      in glycogen. Two regional lymph node metastases were seen microscopically.
      Immunohistochemically these cells were positive for AFP, carcinoembryonic
      antigen, caudal-type homeobox transcription factor 2 and common acute
      lymphoblastic leukemia antigen. The final diagnosis was AFP-producing gastric
      carcinoma with enteroblastic differentiation. 26 months after initial surgery,
      the patient was readmitted to our hospital for gastrointestinal obstruction due
      to lymph node recurrence. 

PMID- 24574941
TI  - Anesthesiology residents' perspective about good teaching--a qualitative needs
      assessment.
AB  - BACKGROUND: Germany, like many other countries, will soon have a shortage of
      qualified doctors. One reason for the dissatisfaction amongst medical residents
      are the relatively unstructured residency training programs despite increasing
      importance of outcome-based education. The aim of our study was to identify
      characteristics and requirements for good teaching during anesthesiology
      residency training from the resident's point of view. METHODS: A consensus
      workshop with residents from all medical universities in Germany was held.
      Participants were allocated to one of the three topics, chosen based on a 2009
      nationwide evaluation of residency. The three topics were (A) characteristics of
      helpful/good teachers, (B) characteristics of helpful/good conditions and (C)
      characteristics of helpful/good curricular structure. Each group followed a
      nominal group technique consensus process to define and rank characteristics for
      a good residency. RESULTS: 31 (79.5%) resident representatives were present. The
      consented results put emphasis on the importance of structured curricula
      including transparent goals and objectives, in training formative assessments and
      quality assurance measures for the program. Residents further long for trained
      trainers with formal teaching qualifications and protected teaching time.
      CONCLUSIONS: Good residency training requires careful consideration of all
      stakeholders' needs. Results reflect and extend previous findings and are at
      least to some degree easily implemented. These findings are an important step to
      establish a broader consensus within the discipline.

PMID- 24574943
TI  - Intestinal neuronal dysplasia type B in adults: a controversial entity.
AB  - Intestinal neuronal dysplasia (IND) is a well-defined entity which raises
      controversy among authors, described as a congenital malformation of
      gastrointestinal innervation and caused by dysplastic embryonal development of
      the enteric nervous system. It is potentially associated with mild and chronic
      gastrointestinal motility disturbances. IND is rarely reported in adults and
      especially elderly patients. The present study reports on the case of a 71-year
      old man suffering from longstanding idiopathic constipation and who was
      misdiagnosed for more than 60 years, despite several hospital admissions and a
      sigmoidectomy in the meantime. On the last admission, the patient presented with
      megacolon, abdominal pain and X-ray finding of bowel obstruction. Due to massive
      large bowel dilatation, an exploratory laparotomy failed to reveal any obvious
      mechanical cause, and a subtotal colectomy and Hartmann's procedure was
      performed. Bowel continuity was performed 3 months later. Analysis of full
      thickness biopsies revealed enlarged myenteric and submucosal neurons as well as
      an increased number of giant cells and increased acetylcholinesterase activity in
      the mucosa. The diagnosis of IND was established. The main diagnostic criteria,
      the underlining pathophysiology and the recommended therapeutic approach of this
      rare entity are extensively reviewed. 

PMID- 24574945
TI  - The effects of endothelial cells-preserving technique on microsurgical vascular
      reconstruction in biliary tract malignancy: report of twenty cases.
AB  - We describe our experience of resectional surgery with microsurgical
      reconstruction of the hepatic arteries in 20 cases with biliary tract malignancy.
      Hepatic artery thrombosis (HAT) is a lethal complication; therefore, it is
      important to perform microsurgical reconstruction safely. Recently, we adopted
      the back wall support suture technique with double needle sutures that does not
      require the damaged short arteries to be turned over. In this technique, each
      stitch is placed from the inner side to the outer side to keep endothelial cells.
      The purpose of this study was to develop safety methods. From 2003 to 2012, 20
      patients with biliary tract malignancy with possible involvement of the hepatic
      arteries underwent resectional surgery with microvascular reconstruction
      (cholangiocarcinoma: n = 15; others: n = 5). For this cohort study, patients were
      divided into two groups: group I (n = 5) included patients who underwent the
      conventional 'twist technique' and group II (n = 15) included patients who
      underwent the microsurgical back wall support suture technique with double needle
      sutures and received gabexate mesilate, a strong serine protease inhibitor (40
      mg/kg/day) for 7 days. We investigated HAT using Doppler ultrasonography for 10
      days. No postoperative mortality was observed. The incidence of HAT was only one
      case in group I, and there was no significant difference between the two groups.
      However, the value of the pulsatile index and acceleration time were
      significantly improved in group II. In conclusion, the back wall support suture
      technique with gabexate mesilate administration during microvascular
      reconstruction was found to be safe. It is important to keep endothelial cells
      healthy for microvascular reconstruction. 

PMID- 24574944
TI  - Olanzapine and Betamethasone Are Effective for the Treatment of Nausea and
      Vomiting due to Metastatic Brain Tumors of Rectal Cancer.
AB  - Brain lesions originating from metastasis of colorectal cancer represent 3-5% of
      all brain metastases and are relatively rare. Of all distant metastases of
      colorectal cancer, those to the liver are detected in 22-29% of cases, while
      those to the lungs are detected in 8-18% of cases. In contrast, brain metastasis
      is quite rare, with a reported incidence ranging from 0.4 to 1.8%. Treatments for
      metastatic brain tumors include surgery, radiotherapy, chemotherapy and
      supportive care with steroids, etc. Untreated patients exhibit a median survival
      of only approximately 1 month. The choice of treatment for brain metastasis
      depends on the number of lesions, the patient's general condition, nerve findings
      and presence of other metastatic lesions. We herein report the case of a 78-year
      old male who presented with brain metastases originating from rectal carcinoma.
      He suffered from nausea, vomiting, anorexia and vertigo during body movement. He
      received antiemetics, glycerol and whole brain radiation therapy; however, these
      treatments proved ineffective. Olanzapine therapy was started at a dose of 1.25
      mg every night. The persistent nausea disappeared the next day, and the frequency
      of vomiting subsequently decreased. The patient was able to consume solid food.
      Olanzapine is an antipsychotic that has recently been used as palliative therapy
      for refractory nausea and vomiting in patients receiving chemotherapy. We
      consider that olanzapine was helpful as a means of supportive care for the
      treatment of nausea and vomiting due to brain metastasis. 

PMID- 24574946
TI  - Pancreatic arteriovenous malformation.
AB  - An unusual case of pancreatic arteriovenous malformation (P-AVM) combined with
      esophageal cancer is reported. A 59-year-old man was admitted with upper
      abdominal pain. Contrast-enhanced computed tomography showed numerous strongly
      enhanced abnormal vessels and a hypovascular lesion in the area of the pancreatic
      tail. Angiographic study of the celiac artery confirmed racemose vascular
      networks in the tail of the pancreas. Endoscopic retrograde pancreatography
      revealed narrowing and displacement of the main pancreatic duct in the tail of
      the pancreas. Screening esophagoscopy showed a 0-IIa+IIc type tumor in the lower
      thoracic esophagus. Histological examination of esophagoscopic biopsies showed
      squamous cell carcinoma. Based on these findings, P-AVM or pancreatic cancer and
      esophageal cancer were diagnosed. Video-assisted thoracoscopic esophagectomy and
      distal pancreatectomy were performed. Histological examination of the resected
      pancreas revealed abundant abnormal vessels with intravascular thrombi. In
      addition, rupture of a dilated pancreatic duct with pancreatic stones and both
      severe atrophy and fibrosis of the pancreatic parenchyma were observed. The final
      diagnoses were P-AVM consequent to severe chronic pancreatitis and esophageal
      carcinoma. The patient's postoperative course was relatively good. 

PMID- 24574947
TI  - Recurrent upside-down stomach after endoscopic repositioning and gastropexy
      treated by laparoscopic surgery.
AB  - Patients with an upside-down stomach usually receive surgical treatment. In high
      risk patients, endoscopic repositioning and gastropexy can be performed. However,
      the risk of recurrence after endoscopic treatment is not known. We treated a case
      of recurrent upside-down stomach after endoscopic therapy that indicated the
      limits of endoscopic treatment and risk of recurrence. An 88-year-old woman was
      treated three times for vomiting in the past. She presented to our hospital with
      periodic vomiting and an inability to eat, and a diagnosis of upside-down stomach
      was made. Endoscopic repositioning and gastropexy were performed. The anterior
      stomach wall was fixed to the abdominal wall in three places as widely as
      possible. Following treatment, she became symptom-free. Three months later, she
      was hospitalized again because of a recurrent upside-down stomach. Laparoscopic
      repair of hernias and gastropexy was performed. Using a laparoscope, two causes
      of recurrence were found. One cause was that the range of adherence between the
      stomach and the abdominal wall was narrow (from the antrum only to the lower
      corpus of stomach), so the upper corpus of stomach was rotated and herniated into
      the esophageal hiatus. The other cause was adhesion between the omentum and the
      esophageal hiatus which caused the stomach to rotate and repeatedly become
      herniated. Although endoscopic treatment for upside-down stomach can be a useful
      alternative method in high-risk patients, its ability to prevent recurrence is
      limited. Moreover, a repeated case caused by adhesions has risks of recurrence. 

PMID- 24574948
TI  - A simple and safe procedure to repair rectal prolapse perineally using stapling
      devices.
AB  - Rectal prolapses are not life-threatening, however the bleeding and fecal
      incontinence associated with them significantly erode quality of life and can
      cause concern among patients' caregivers in nursing homes. Many procedures have
      been reported that repair rectal prolapses, and the procedure used depends on the
      severity of the prolapse; however, the treatments are yet to be established. Here
      we report a simple and safe procedure to repair rectal prolapse perineally using
      stapling devices. We performed this procedure on 5 patients within a short time.
      All patients were followed up for over 24 months and none had any recurrences of
      their rectal prolapses. No complications occurred during the operations and
      postoperative periods. Most patients who have prolapses are elderly and fragile,
      so the treatment must be easy, safe, and rapid. While rectal prolapse is not life
      threatening, the goal of treatment is to alleviate its symptoms. The procedure we
      describe is consistent with this concept. We suggest that this procedure, which
      uses surgical stapling devices, might be a better option for the treatment of
      complete rectal prolapse. We will continue to surgically correct complete rectal
      prolapses and investigate the long-term outcomes of the procedure. 

PMID- 24574950
TI  - Gastrointestinal endometriosis causing subacute intestinal obstruction with
      gradual development of weight loss and misdiagnosed as irritable bowel syndrome.
AB  - Both endometriosis and irritable bowel syndrome (IBS) are commonly found in young
      women and the diagnosis of either is challenging. Alarm symptoms can exclude the
      diagnosis of IBS, but their onset may be insidious and often no evidence of
      organic disease may be found. We present a patient with a 4-year history of
      presumed IBS, absent gynecological symptoms, negative gastrointestinal as well as
      gynecological testing who developed the only alarm symptom of weight loss and was
      eventually found to have endometriosis of the small intestine. This case
      illustrates the need for constant vigilance in patients with IBS. 

PMID- 24574949
TI  - Suspected de novo Hepatitis B in a Patient Receiving Anti-Tumor Necrosis Factor
      Alpha Therapy for the Treatment of Crohn's Disease.
AB  - We report a 45-year-old female patient who developed acute hepatic disorder
      during anti-tumor necrosis factor alpha therapy for the treatment of Crohn's
      disease (CD). She was diagnosed as colonic CD and placed on infliximab (IFX). She
      was negative for hepatitis B surface antigen at the initiation of IFX therapy,
      but developed acute hepatitis after the 30th administration of IFX 4 years and 1
      month after the first administration. She was suspected to have had occult
      hepatitis B virus infection before IFX therapy, and de novo hepatitis B was
      considered the most likely diagnosis. Hepatitis subsided after discontinuation of
      anti-tumor necrosis factor alpha therapy and initiation of treatment with
      entecavir. She started to receive adalimumab to prevent relapse of CD. She has
      continued maintenance therapy with entecavir and adalimumab and has since been
      asymptomatic. As de novo hepatitis B may be fatal, virological testing for
      hepatitis B is essential for patients who are being considered for treatment that
      may weaken the immune system. 

PMID- 24574951
TI  - Foreign material in the gastrointestinal tract: cocaine packets.
AB  - Smuggling drugs by swallowing or inserting into a body cavity is not only a
      serious and growing international crime, but can also lead to lethal medical
      complications. The most common cause of death in 'body packers', people
      transporting drugs by ingesting a packet into the gastrointestinal tract, is
      acute drug toxicity from a ruptured packet. However, more than 30 years after the
      initial report of body packing, there is still no definitive treatment protocol
      for the management of this patient group. The treatment strategy is determined
      according to the particular condition of the patient and the clinical experience
      of the treatment center. Surgical intervention is also less common now, due to
      both the use of improved packaging materials among smugglers and a shift towards
      a more conservative medical approach. Herein, we report a case of toxicity from
      ingested packets of cocaine that leaked and, despite surgery, resulted in exitus
      of the patient. 

PMID- 24574953
TI  - Antisaccade performance in schizophrenia: a neural model of decision making in
      the superior colliculus.
AB  - Antisaccade performance deficits in schizophrenia are generally interpreted as an
      impaired top-down inhibitory signal failing to suppress the erroneous response.
      We recorded the antisaccade performance (error rates and latencies) of healthy
      and schizophrenia subjects performing the mirror antisaccade task. A neural rise
      to-threshold model of antisaccade performance was developed to uncover the
      biophysical mechanisms giving rise to the observed deficits in schizophrenia.
      Schizophrenia patients displayed greater variability in the antisaccade and
      corrected antisaccade latency distributions, increased error rates and decreased
      corrected errors, relative to healthy participants. Our model showed that (1)
      increased variability is due to a more noisy accumulation of information by
      schizophrenia patients, but their confidence level required before making a
      decision is unaffected, and (2) competition between the correct and erroneous
      decision processes, and not a third top-down inhibitory signal suppressing the
      erroneous response, accounts for the antisaccade performance of healthy and
      schizophrenia subjects. Local competition further ensured that a correct
      antisaccade is never followed by an error prosaccade. 

PMID- 24574952
TI  - Event-driven contrastive divergence for spiking neuromorphic systems.
AB  - Restricted Boltzmann Machines (RBMs) and Deep Belief Networks have been
      demonstrated to perform efficiently in a variety of applications, such as
      dimensionality reduction, feature learning, and classification. Their
      implementation on neuromorphic hardware platforms emulating large-scale networks
      of spiking neurons can have significant advantages from the perspectives of
      scalability, power dissipation and real-time interfacing with the environment.
      However, the traditional RBM architecture and the commonly used training
      algorithm known as Contrastive Divergence (CD) are based on discrete updates and
      exact arithmetics which do not directly map onto a dynamical neural substrate.
      Here, we present an event-driven variation of CD to train a RBM constructed with
      Integrate & Fire (I&F) neurons, that is constrained by the limitations of
      existing and near future neuromorphic hardware platforms. Our strategy is based
      on neural sampling, which allows us to synthesize a spiking neural network that
      samples from a target Boltzmann distribution. The recurrent activity of the
      network replaces the discrete steps of the CD algorithm, while Spike Time
      Dependent Plasticity (STDP) carries out the weight updates in an online,
      asynchronous fashion. We demonstrate our approach by training an RBM composed of
      leaky I&F neurons with STDP synapses to learn a generative model of the MNIST
      hand-written digit dataset, and by testing it in recognition, generation and cue
      integration tasks. Our results contribute to a machine learning-driven approach
      for synthesizing networks of spiking neurons capable of carrying out practical,
      high-level functionality. 

PMID- 24574954
TI  - Adult subventricular zone neural stem cells as a potential source of dopaminergic
      replacement neurons.
AB  - Clinical trials engrafting human fetal ventral mesencephalic tissue have
      demonstrated, in principle, that cell replacement therapy provides substantial
      long-lasting improvement of motor impairments generated by Parkinson's Disease
      (PD). The use of fetal tissue is not practical for widespread clinical
      implementation of this therapy, but stem cells are a promising alternative source
      for obtaining replacement cells. The ideal stem cell source has yet to be
      established and, in this review, we discuss the potential of neural stem cells in
      the adult subventricular zone (SVZ) as an autologous source of replacement cells.
      We identify three key challenges for further developing this potential source of
      replacement cells: (1) improving survival of transplanted cells, (2) suppressing
      glial progenitor proliferation and survival, and (3) developing methods to
      efficiently produce dopaminergic neurons. Subventricular neural stem cells
      naturally produce a dopaminergic interneuron phenotype that has an apparent lack
      of vulnerability to PD-mediated degeneration. We also discuss whether olfactory
      bulb dopaminergic neurons derived from adult SVZ neural stem cells are a suitable
      source for cell replacement strategies. 

PMID- 24574955
TI  - Adult neurogenesis in brain repair: cellular plasticity vs. cellular replacement.

PMID- 24574957
TI  - Orexin A and orexin receptor 1 axonal traffic in dorsal roots at the CNS/PNS
      interface.
AB  - Hypothalamic orexin/hypocretin neurons send long axonal projections through the
      dorsal spinal cord in lamina I-II of the dorsal horn (DH) at the interface with
      the peripheral nervous system (PNS). We show that in the DH OXA fibers colocalize
      with substance P (SP) positive afferents of dorsal root ganglia (DRG) neurons
      known to mediate sensory processing. Further, OR1 is expressed in p75(NTR) and SP
      positive DRG neurons, suggesting a potential signaling pathway between orexin and
      DRG neurons. Interestingly, DRG sensory neurons have a distinctive bifurcating
      axon where one branch innervates the periphery and the other one the spinal cord
      (pseudo-unipolar neurons), allowing for potential functional coupling of distinct
      targets. We observe that OR1 is transported selectively from DRG toward the
      spinal cord, while OXA is accumulated retrogradely toward the DRG. We hence
      report a rare situation of asymmetrical neuropeptide receptor distribution
      between axons projected by a single neuron. These molecular and cellular data are
      consistent with the role of OXA/OR1 in sensory processing, including DRG neuronal
      modulation, and support the potential existence of an OX/HCRT circuit between CNS
      and PNS. 

PMID- 24574956
TI  - The impact of environmental factors in severe psychiatric disorders.
AB  - During the last decades, schizophrenia has been regarded as a developmental
      disorder. The neurodevelopmental hypothesis proposes schizophrenia to be related
      to genetic and environmental factors leading to abnormal brain development during
      the pre- or postnatal period. First disease symptoms appear in early adulthood
      during the synaptic pruning and myelination process. Meta-analyses of structural
      MRI studies revealing hippocampal volume deficits in first-episode patients and
      in the longitudinal disease course confirm this hypothesis. Apart from the
      influence of risk genes in severe psychiatric disorders, environmental factors
      may also impact brain development during the perinatal period. Several
      environmental factors such as antenatal maternal virus infections, obstetric
      complications entailing hypoxia as common factor or stress during
      neurodevelopment have been identified to play a role in schizophrenia and bipolar
      disorder, possibly contributing to smaller hippocampal volumes. In major
      depression, psychosocial stress during the perinatal period or in adulthood is an
      important trigger. In animal studies, chronic stress or repeated administration
      of glucocorticoids have been shown to induce degeneration of glucocorticoid
      sensitive hippocampal neurons and may contribute to the pathophysiology of
      affective disorders. Epigenetic mechanisms altering the chromatin structure such
      as histone acetylation and DNA methylation may mediate effects of environmental
      factors to transcriptional regulation of specific genes and be a prominent factor
      in gene-environmental interaction. In animal models, gene-environmental
      interaction should be investigated more intensely to unravel pathophysiological
      mechanisms. These findings may lead to new therapeutic strategies influencing
      epigenetic targets in severe psychiatric disorders. 

PMID- 24574960
TI  - Aberrant disgust response and immune reactivity in cocaine-dependent men might
      uncover deranged serotoninergic activity.

PMID- 24574958
TI  - Orexin, cardio-respiratory function, and hypertension.
AB  - In this review we focus on the role of orexin in cardio-respiratory functions and
      its potential link to hypertension. (1) Orexin, cardiovascular function, and
      hypertension. In normal rats, central administration of orexin can induce
      significant increases in arterial blood pressure (ABP) and sympathetic nerve
      activity (SNA), which can be blocked by orexin receptor antagonists. In
      spontaneously hypertensive rats (SHRs), antagonizing orexin receptors can
      significantly lower blood pressure under anesthetized or conscious conditions.
      (2) Orexin, respiratory function, and central chemoreception. The prepro-orexin
      knockout mouse has a significantly attenuated ventilatory CO2 chemoreflex, and in
      normal rats, central application of orexin stimulates breathing while blocking
      orexin receptors decreases the ventilatory CO2 chemoreflex. Interestingly, SHRs
      have a significantly increased ventilatory CO2 chemoreflex relative to
      normotensive WKY rats and blocking both orexin receptors can normalize this
      exaggerated response. (3) Orexin, central chemoreception, and hypertension. SHRs
      have higher ABP and SNA along with an enhanced ventilatory CO2 chemoreflex.
      Treating SHRs by blocking both orexin receptors with oral administration of an
      antagonist, almorexant (Almxt), can normalize the CO2 chemoreflex and
      significantly lower ABP and SNA. We interpret these results to suggest that the
      orexin system participates in the pathogenesis and maintenance of high blood
      pressure in SHRs, and the central chemoreflex may be a causal link to the
      increased SNA and ABP in SHRs. Modulation of the orexin system could be a
      potential target in treating some forms of hypertension. 

PMID- 24574959
TI  - Loss of mTOR repressors Tsc1 or Pten has divergent effects on excitatory and
      inhibitory synaptic transmission in single hippocampal neuron cultures.
AB  - The Pten and Tsc1 genes both encode proteins that repress mechanistic target of
      rapamycin (mTOR) signaling. Disruption of either gene in the brain results in
      epilepsy and autism-like symptoms in humans and mouse models, therefore it is
      important to understand the molecular and physiological events that lead from
      gene disruption to disease phenotypes. Given the similar roles these two
      molecules play in the regulation of cellular growth and the overlap in the
      phenotypes that result from their loss, we predicted that the deletion of either
      the Pten or Tsc1 gene from autaptic hippocampal neurons would have similar
      effects on neuronal morphology and synaptic transmission. Accordingly, we found
      that loss of either Pten or Tsc1 caused comparable increases in soma size,
      dendrite length and action potential properties. However, the effects of Pten and
      Tsc1 loss on synaptic transmission were different. Loss of Pten lead to an
      increase in both excitatory and inhibitory neurotransmission, while loss of Tsc1
      did not affect excitatory neurotransmission and reduced inhibitory transmission
      by decreasing mIPSC amplitude. Although the loss of Pten or Tsc1 both increased
      downstream mTORC1 signaling, phosphorylation of Akt was increased in Pten-ko and
      decreased in Tsc1-ko neurons, potentially accounting for the different effects on
      synaptic transmission. Despite the different effects at the synaptic level, our
      data suggest that loss of Pten or Tsc1 may both lead to an increase in the ratio
      of excitation to inhibition at the network level, an effect that has been
      proposed to underlie both epilepsy and autism. 

PMID- 24574962
TI  - Predicted overlapping microRNA regulators of acetylcholine packaging and
      degradation in neuroinflammation-related disorders.
AB  - MicroRNAs (miRNAs) can notably control many targets each and regulate entire
      cellular pathways, but whether miRNAs can regulate complete neurotransmission
      processes is largely unknown. Here, we report that miRNAs with complementary
      sequence motifs to the key genes involved in acetylcholine (ACh) synthesis and/or
      packaging show massive overlap with those regulating ACh degradation. To address
      this topic, we first searched for miRNAs that could target the 3'-untranslated
      regions of the choline acetyltransferase (ChAT) gene that controls ACh synthesis;
      the vesicular ACh transporter (VAChT), encoded from an intron in the ChAT gene
      and the ACh hydrolyzing genes acetyl- and/or butyrylcholinesterase (AChE, BChE).
      Intriguingly, we found that many of the miRNAs targeting these genes are primate
      specific, and that changes in their levels associate with inflammation, anxiety,
      brain damage, cardiac, neurodegenerative, or pain-related syndromes. To validate
      the in vivo relevance of this dual interaction, we selected the evolutionarily
      conserved miR-186, which targets both the stress-inducible soluble "readthrough"
      variant AChE-R and the major peripheral cholinesterase BChE. We exposed mice to
      predator scent stress and searched for potential associations between consequent
      changes in their miR-186, AChE-R, and BChE levels. Both intestinal miR-186 as
      well as BChE and AChE-R activities were conspicuously elevated 1 week post
      exposure, highlighting the previously unknown involvement of miR-186 and BChE in
      psychological stress responses. Overlapping miRNA regulation emerges from our
      findings as a recently evolved surveillance mechanism over cholinergic
      neurotransmission in health and disease; and the corresponding miRNA details and
      disease relevance may serve as a useful resource for studying the molecular
      mechanisms underlying this surveillance. 

PMID- 24574961
TI  - Early-life stress impacts the developing hippocampus and primes seizure
      occurrence: cellular, molecular, and epigenetic mechanisms.
AB  - Early-life stress includes prenatal, postnatal, and adolescence stress. Early
      life stress can affect the development of the hypothalamic-pituitary-adrenal
      (HPA) axis, and cause cellular and molecular changes in the developing
      hippocampus that can result in neurobehavioral changes later in life.
      Epidemiological data implicate stress as a cause of seizures in both children and
      adults. Emerging evidence indicates that both prenatal and postnatal stress can
      prime the developing brain for seizures and an increase in epileptogenesis. This
      article reviews the cellular and molecular changes encountered during prenatal
      and postnatal stress, and assesses the possible link between these changes and
      increases in seizure occurrence and epileptogenesis in the developing
      hippocampus. In addititon, the priming effect of prenatal and postnatal stress
      for seizures and epileptogenesis is discussed. Finally, the roles of epigenetic
      modifications in hippocampus and HPA axis programming, early-life stress, and
      epilepsy are discussed. 

PMID- 24574964
TI  - MicroRNA responses to focal cerebral ischemia in male and female mouse brain.
AB  - Stroke occurs with greater frequency in men than in women across diverse ethnic
      backgrounds and nationalities. Work from our lab and others have revealed a sex
      specific sensitivity to cerebral ischemia whereby males exhibit a larger extent
      of brain damage resulting from an ischemic event compared to females. Previous
      studies revealed that microRNA (miRNA) expression is regulated by cerebral
      ischemia in males; however, no studies to date have examined the effect of
      ischemia on miRNA responses in females. Thus, we examined miRNA responses in male
      and female brain in response to cerebral ischemia using miRNA arrays. These
      studies revealed that in male and female brains, ischemia leads to both a
      universal miRNA response as well as a sexually distinct response to challenge.
      Target prediction analysis of the miRNAs increased in male or female ischemic
      brain reveal sex-specific differences in gene targets and protein pathways. These
      data support that the mechanisms underlying sexually dimorphic responses to
      cerebral ischemia includes distinct changes in miRNAs in male and female brain,
      in addition to a miRNA signature response to ischemia that is common to both. 

PMID- 24574963
TI  - miRNAs and viroids utilize common strategies in genetic signal transfer.

PMID- 24574965
TI  - Chronic hypoxia induces the activation of the Wnt/beta-catenin signaling pathway
      and stimulates hippocampal neurogenesis in wild-type and APPswe-PS1DeltaE9
      transgenic mice in vivo.
AB  - Hypoxia modulates proliferation and differentiation of cultured embryonic and
      adult stem cells, an effect that includes beta-catenin, a key component of the
      canonical Wnt signaling pathway. Here we studied the effect of mild hypoxia on
      the activity of the Wnt/beta-catenin signaling pathway in the hippocampus of
      adult mice in vivo. The hypoxia-inducible transcription factor-1alpha (HIF
      1alpha) was analyzed as a molecular control of the physiological hypoxic
      response. Exposure to chronic hypoxia (10% oxygen for 6-72 h) stimulated the
      activation of the Wnt/beta-catenin signaling pathway. Because the Wnt/beta
      catenin pathway is a positive modulator of adult neurogenesis, we evaluated
      whether chronic hypoxia was able to stimulate neurogenesis in the subgranular
      zone (SGZ) of the hippocampal dentate gyrus. Results indicate that hypoxia
      increased cell proliferation and neurogenesis in adult wild-type mice as
      determined by Ki67 staining, Bromodeoxyuridine (BrdU) incorporation and double
      labeling with doublecortin (DCX). Chronic hypoxia also induced neurogenesis in a
      double transgenic APPswe-PS1DeltaE9 mouse model of Alzheimer's disease (AD),
      which shows decreased levels of neurogenesis in the SGZ. Our results show for the
      first time that exposure to hypoxia in vivo can induce the activation of the
      Wnt/beta-catenin signaling cascade in the hippocampus, suggesting that mild
      hypoxia may have a therapeutic value in neurodegenerative disorders associated
      with altered Wnt signaling in the brain and also in pathological conditions in
      which hippocampal neurogenesis is impaired. 

PMID- 24574968
TI  - Epigenetic aspects of telocytes/cordocytes: jacks of all trades, masters of most.

PMID- 24574969
TI  - Activity-dependent endogenous taurine release facilitates excitatory
      neurotransmission in the neocortical marginal zone of neonatal rats.
AB  - In the developing cerebral cortex, the marginal zone (MZ), consisting of early
      generated neurons such as Cajal-Retzius cells, plays an important role in cell
      migration and lamination. There is accumulating evidence of widespread excitatory
      neurotransmission mediated by gamma-aminobutyric acid (GABA) in the MZ. Cajal
      Retzius cells express not only GABAA receptors but also alpha2/beta subunits of
      glycine receptors, and exhibit glycine receptor-mediated depolarization due to
      high [Cl(-)]i. However, the physiological roles of glycine receptors and their
      endogenous agonists during neurotransmission in the MZ are yet to be elucidated.
      To address this question, we performed optical imaging from the MZ using the
      voltage-sensitive dye JPW1114 on tangential neocortical slices of neonatal rats.
      A single electrical stimulus evoked an action-potential-dependent optical signal
      that spread radially over the MZ. The amplitude of the signal was not affected by
      glutamate receptor blockers, but was suppressed by either GABAA or glycine
      receptor antagonists. Combined application of both antagonists nearly abolished
      the signal. Inhibition of Na(+), K(+)-2Cl(-) cotransporter by 20 uM bumetanide
      reduced the signal, indicating that this transporter contributes to excitation.
      Analysis of the interstitial fluid obtained by microdialysis from tangential
      neocortical slices with high-performance liquid chromatography revealed that GABA
      and taurine, but not glycine or glutamate, were released in the MZ in response to
      the electrical stimulation. The ambient release of taurine was reduced by the
      addition of a voltage-sensitive Na(+) channel blocker. Immunohistochemistry and
      immunoelectron microscopy indicated that taurine was stored both in Cajal-Retzius
      and non-Cajal-Retzius cells in the MZ, but was not localized in presynaptic
      structures. Our results suggest that activity-dependent non-synaptic release of
      endogenous taurine facilitates excitatory neurotransmission through activation of
      glycine receptors in the MZ. 

PMID- 24574967
TI  - MicroRNAs regulate neuronal plasticity and are involved in pain mechanisms.
AB  - MicroRNAs (miRNAs) are emerging as master regulators of gene expression in the
      nervous system where they contribute not only to brain development but also to
      neuronal network homeostasis and plasticity. Their function is the result of a
      cascade of events including miRNA biogenesis, target recognition, and translation
      inhibition. It has been suggested that miRNAs are major switches of the genome
      owing to their ability to regulate multiple genes at the same time. This
      regulation is essential for normal neuronal activity and, when affected, can lead
      to drastic pathological conditions. As an example, we illustrate how deregulation
      of miRNAs can affect neuronal plasticity leading to chronic pain. The origin of
      pain and its dual role as a key physiological function and a debilitating disease
      has been highly debated until now. The incidence of chronic pain is estimated to
      be 20-25% worldwide, thus making it a public health problem. Chronic pain can be
      considered as a form of maladaptive plasticity. Long-lasting modifications
      develop as a result of global changes in gene expression, and are thus likely to
      be controlled by miRNAs. Here, we review the literature on miRNAs and their
      targets responsible for maladaptive plasticity in chronic pain conditions. In
      addition, we conduct a retrospective analysis of miRNA expression data published
      for different pain models, taking into account recent progress in our
      understanding of the role of miRNAs in neuronal plasticity. 

PMID- 24574966
TI  - Insulin dysfunction and Tau pathology.
AB  - The neuropathological hallmarks of Alzheimer's disease (AD) include senile
      plaques of beta-amyloid (Abeta) peptides (a cleavage product of the Amyloid
      Precursor Protein, or APP) and neurofibrillary tangles (NFT) of
      hyperphosphorylated Tau protein assembled in paired helical filaments (PHF). NFT
      pathology is important since it correlates with the degree of cognitive
      impairment in AD. Only a small proportion of AD is due to genetic variants,
      whereas the large majority of cases (~99%) is late onset and sporadic in origin.
      The cause of sporadic AD is likely to be multifactorial, with external factors
      interacting with biological or genetic susceptibilities to accelerate the
      manifestation of the disease. Insulin dysfunction, manifested by diabetes
      mellitus (DM) might be such factor, as there is extensive data from
      epidemiological studies suggesting that DM is associated with an increased
      relative risk for AD. Type 1 diabetes (T1DM) and type 2 diabetes (T2DM) are known
      to affect multiple cognitive functions in patients. In this context,
      understanding the effects of diabetes on Tau pathogenesis is important since Tau
      pathology show a strong relationship to dementia in AD, and to memory loss in
      normal aging and mild cognitive impairment. Here, we reviewed preclinical studies
      that link insulin dysfunction to Tau protein pathogenesis, one of the major
      pathological hallmarks of AD. We found more than 30 studies reporting Tau
      phosphorylation in a mouse or rat model of insulin dysfunction. We also payed
      attention to potential sources of artifacts, such as hypothermia and anesthesia,
      that were demonstrated to results in Tau hyperphosphorylation and could major
      confounding experimental factors. We found that very few studies reported the
      temperature of the animals, and only a handful did not use anesthesia. Overall,
      most published studies showed that insulin dysfunction can promote Tau
      hyperphosphorylation and pathology, both directly and indirectly, through
      hypothermia. 

PMID- 24574970
TI  - Rescue of tau-induced synaptic transmission pathology by paclitaxel.
AB  - Behavioral and electrophysiological studies of Alzheimer's disease (AD) and other
      tauopathies have revealed that the onset of cognitive decline correlates better
      with synaptic dysfunctions than with hallmark pathologies such as extracellular
      amyloid-beta plaques, intracellular hyperphosphorylated tau or neuronal loss.
      Recent experiments have also demonstrated that anti-cancer microtubule (MT)
      stabilizing drugs can rescue tau-induced behavioral decline and hallmark neuron
      pathologies. Nevertheless, the mechanisms underlying tau-induced synaptic
      dysfunction as well as those involved in the rescue of cognitive decline by MTs
      stabilizing drugs remain unclear. Here we began to study these mechanisms using
      the glutaminergic sensory-motoneuron synapse derived from Aplysia ganglia,
      electrophysiological methods, the expression of mutant-human tau (mt-htau) either
      pre or postsynaptically and the antimitotic drug paclitaxel. Expression of mt
      htau in the presynaptic neurons led to reduced excitatory postsynaptic potential
      (EPSP) amplitude generated by rested synapses within 3 days of mt-htau
      expression, and to deeper levels of homosynaptic depression. mt-htau-induced
      synaptic weakening correlated with reduced releasable presynaptic vesicle pools
      as revealed by the induction of asynchronous neurotransmitter release by
      hypertonic sucrose solution. Paclitaxel totally rescued tau-induced synaptic
      weakening by maintaining the availability of the presynaptic vesicle stores.
      Postsynaptic expression of mt-htau did not impair the above described synaptic
      transmission parameters for up to 5 days. Along with earlier confocal microscope
      observations from our laboratory, these findings suggest that tau-induced
      synaptic dysfunction is the outcome of impaired axoplasmic transport and the
      ensuing reduction in the releasable presynaptic vesicle stores rather than the
      direct effects of mt-htau or paclitaxel on the synaptic release mechanisms. 

PMID- 24574971
TI  - Elongation factor-2 phosphorylation in dendrites and the regulation of dendritic
      mRNA translation in neurons.
AB  - Neuronal activity results in long lasting changes in synaptic structure and
      function by regulating mRNA translation in dendrites. These activity dependent
      events yield the synthesis of proteins known to be important for synaptic
      modifications and diverse forms of synaptic plasticity. Worthy of note, there is
      accumulating evidence that the eukaryotic Elongation Factor 2 Kinase
      (eEF2K)/eukaryotic Elongation Factor 2 (eEF2) pathway may be strongly involved in
      this process. Upon activation, eEF2K phosphorylates and thereby inhibits eEF2,
      resulting in a dramatic reduction of mRNA translation. eEF2K is activated by
      elevated levels of calcium and binding of Calmodulin (CaM), hence its alternative
      name calcium/CaM-dependent protein kinase III (CaMKIII). In dendrites, this
      process depends on glutamate signaling and N-methyl-D-aspartate receptor (NMDAR)
      activation. Interestingly, it has been shown that eEF2K can be activated in
      dendrites by metabotropic glutamate receptor (mGluR) 1/5 signaling, as well.
      Therefore, neuronal activity can induce local proteomic changes at the
      postsynapse by altering eEF2K activity. Well-established targets of eEF2K in
      dendrites include brain-derived neurotrophic factor (BDNF), activity-regulated
      cytoskeletal-associated protein (Arc), the alpha subunit of calcium/CaM-dependent
      protein kinase II (alphaCaMKII), and microtubule-associated protein 1B (MAP1B),
      all of which have well-known functions in different forms of synaptic plasticity.
      In this review we will give an overview of the involvement of the eEF2K/eEF2
      pathway at dendrites in regulating the translation of dendritic mRNA in the
      context of altered NMDAR- and neuronal activity, and diverse forms of synaptic
      plasticity, such as metabotropic glutamate receptor-dependent-long-term
      depression (mGluR-LTD). For this, we draw on studies carried out both in vitro
      and in vivo. 

PMID- 24574972
TI  - Optogenetic activation of nigral inhibitory inputs to motor thalamus in the mouse
      reveals classic inhibition with little potential for rebound activation.
AB  - The inhibitory output from the internal pallidum and substantia nigra to the
      thalamus forms an important link in the transmission of basal ganglia processing
      to cortex. Two hypotheses consider either inhibition of thalamic activity or
      thalamic excitation via post-inhibitory rebound burst firing as the functional
      mode of this link. We used optogenetics to characterize the synaptic properties
      of nigral input to motor thalamus in adult mouse brain slices, and to determine
      in what conditions the nigral inhibition of motor thalamus is transmitted via
      inhibition or rebound firing. Our results are more consistent with graded
      inhibition of spiking for conditions expected in normal awake animals, because
      inhibitory potentials from nigral input were generally not sufficient to elicit
      rebound spikes when the thalamic neurons were actively firing. However, with
      bursty or fast trains of nigral input low-threshold rebound spike bursts could be
      triggered for low levels of excitation. This may form the basis of pathological
      burst generation and transmission in parkinsonian conditions. 

PMID- 24574973
TI  - Inflammatory stimulation preserves physiological properties of retinal ganglion
      cells after optic nerve injury.
AB  - Axonal injury in the optic nerve is associated with retinal ganglion cell (RGC)
      degeneration and irreversible loss of vision. However, inflammatory stimulation
      (IS) by intravitreal injection of Pam3Cys transforms RGCs into an active
      regenerative state enabling these neurons to survive injury and to regenerate
      axons into the injured optic nerve. Although morphological changes have been well
      studied, the functional correlates of RGCs transformed either into a de- or
      regenerating state at a sub-cellular level remain unclear. In the current study,
      we investigated the signal propagation in single intraretinal axons as well as
      characteristic activity features of RGCs in a naive, a degenerative or a
      regenerative state in ex vivo retinae 1 week after either optic nerve cut alone
      (ONC) or additional IS (ONC + IS). Recordings of single RGCs using high-density
      microelectrode arrays demonstrate that the mean intraretinal axonal conduction
      velocity significantly decreased within the first week after ONC. In contrast,
      when ONC was accompanied by regenerative Pam3Cys treatment the mean intraretinal
      velocity was undistinguishable from control RGCs, indicating a protective effect
      on the proximal axon. Spontaneous RGC activity decreased for the two most
      numerous RGC types (ON- and OFF-sustained cells) within one post-operative week,
      but did not significantly increase in RGCs after IS. The analysis of light
      induced activity revealed that RGCs in ONC animals respond on average later and
      with fewer spikes than control RGCs. IS significantly improved the responsiveness
      of the two studied RGC types. These results show that the transformation into a
      regenerative state by IS preserves, at least transiently, the physiological
      functional properties of injured RGCs. 

PMID- 24574974
TI  - Parallel neural pathways in higher visual centers of the Drosophila brain that
      mediate wavelength-specific behavior.
AB  - Compared with connections between the retinae and primary visual centers,
      relatively less is known in both mammals and insects about the functional
      segregation of neural pathways connecting primary and higher centers of the
      visual processing cascade. Here, using the Drosophila visual system as a model,
      we demonstrate two levels of parallel computation in the pathways that connect
      primary visual centers of the optic lobe to computational circuits embedded
      within deeper centers in the central brain. We show that a seemingly simple
      achromatic behavior, namely phototaxis, is under the control of several
      independent pathways, each of which is responsible for navigation towards unique
      wavelengths. Silencing just one pathway is enough to disturb phototaxis towards
      one characteristic monochromatic source, whereas phototactic behavior towards
      white light is not affected. The response spectrum of each demonstrable pathway
      is different from that of individual photoreceptors, suggesting subtractive
      computations. A choice assay between two colors showed that these pathways are
      responsible for navigation towards, but not for the detection itself of, the
      monochromatic light. The present study provides novel insights about how visual
      information is separated and processed in parallel to achieve robust control of
      an innate behavior. 

PMID- 24574976
TI  - Delineation of motoneuron subgroups supplying individual eye muscles in the human
      oculomotor nucleus.
AB  - The oculomotor nucleus (nIII) contains the motoneurons of medial, inferior, and
      superior recti (MR, IR, and SR), inferior oblique (IO), and levator palpebrae
      (LP) muscles. The delineation of motoneuron subgroups for each muscle is well
      known in monkey, but not in human. We studied the transmitter inputs to human
      nIII and the trochlear nucleus (nIV), which innervates the superior oblique
      muscle (SO), to outline individual motoneuron subgroups. Parallel series of
      sections from human brainstems were immunostained for different markers: choline
      acetyltransferase combined with glutamate decarboxylase (GAD), calretinin (CR) or
      glycine receptor. The cytoarchitecture was visualized with cresyl violet, Gallyas
      staining and expression of non-phosphorylated neurofilaments. Apart from nIV,
      seven subgroups were delineated in nIII: the central caudal nucleus (CCN), a
      dorsolateral (DL), dorsomedial (DM), central (CEN), and ventral (VEN) group, the
      nucleus of Perlia (NP) and the non-preganglionic centrally projecting Edinger
      Westphal nucleus (EWcp). DL, VEN, NP, and EWcp were characterized by a strong
      supply of GAD-positive terminals, in contrast to DM, CEN, and nIV. CR-positive
      terminals and fibers were confined to CCN, CEN, and NP. Based on location and
      histochemistry of the motoneuron subgroups in monkey, CEN is considered as the SR
      and IO motoneurons, DL and VEN as the B- and A-group of MR motoneurons,
      respectively, and DM as IR motoneurons. A good correlation between monkey and man
      is seen for the CR input, which labels only motoneurons of eye muscles
      participating in upgaze (SR, IO, and LP). The CCN contained LP motoneurons, and
      nIV those of SO. This study provides a map of the individual subgroups of
      motoneurons in human nIII for the first time, and suggests that NP may contain
      upgaze motoneurons. Surprisingly, a strong GABAergic input to human MR
      motoneurons was discovered, which is not seen in monkey and may indicate a
      functional oculomotor specialization. 

PMID- 24574978
TI  - Neuromusic research: some benefits of incorporating basic research on the
      neurobiology of auditory learning and memory.

PMID- 24574975
TI  - Constancy and trade-offs in the neuroanatomical and metabolic design of the
      cerebral cortex.
AB  - Mammalian brains span about four orders of magnitude in cortical volume and have
      to operate in different environments that require diverse behavioral skills.
      Despite these geometric and behavioral diversities, the examination of cerebral
      cortex across species reveals that it contains a substantial number of conserved
      characteristics that are associated with neuroanatomy and metabolism, i.e., with
      neuronal connectivity and function. Some of these cortical constants or
      invariants have been known for a long time but not sufficiently appreciated, and
      others were only recently discovered. The focus of this review is to present the
      cortical invariants and discuss their role in the efficient information
      processing. Global conservation in neuroanatomy and metabolism, as well as their
      correlated regional and developmental variability suggest that these two parallel
      systems are mutually coupled. It is argued that energetic constraint on cortical
      organization can be strong if cerebral blood supplied is either below or above a
      certain level, and it is rather soft otherwise. Moreover, because maximization or
      minimization of parameters associated with cortical connectivity, function and
      cost often leads to conflicts in design, it is argued that the architecture of
      the cerebral cortex is a result of structural and functional compromises. 

PMID- 24574979
TI  - Spike sorting for polytrodes: a divide and conquer approach.
AB  - In order to determine patterns of neural activity, spike signals recorded by
      extracellular electrodes have to be clustered (sorted) with the aim of ensuring
      that each cluster represents all the spikes generated by an individual neuron.
      Many methods for spike sorting have been proposed but few are easily applicable
      to recordings from polytrodes which may have 16 or more recording sites. As with
      tetrodes, these are spaced sufficiently closely that signals from single neurons
      will usually be recorded on several adjacent sites. Although this offers a better
      chance of distinguishing neurons with similarly shaped spikes, sorting is
      difficult in such cases because of the high dimensionality of the space in which
      the signals must be classified. This report details a method for spike sorting
      based on a divide and conquer approach. Clusters are initially formed by
      assigning each event to the channel on which it is largest. Each channel-based
      cluster is then sub-divided into as many distinct clusters as possible. These are
      then recombined on the basis of pairwise tests into a final set of clusters.
      Pairwise tests are also performed to establish how distinct each cluster is from
      the others. A modified gradient ascent clustering (GAC) algorithm is used to do
      the clustering. The method can sort spikes with minimal user input in times
      comparable to real time for recordings lasting up to 45 min. Our results
      illustrate some of the difficulties inherent in spike sorting, including changes
      in spike shape over time. We show that some physiologically distinct units may
      have very similar spike shapes. We show that RMS measures of spike shape
      similarity are not sensitive enough to discriminate clusters that can otherwise
      be separated by principal components analysis (PCA). Hence spike sorting based on
      least-squares matching to templates may be unreliable. Our methods should be
      applicable to tetrodes and scalable to larger multi-electrode arrays (MEAs). 

PMID- 24574977
TI  - Pyramidal cells in V1 of African rodents are bigger, more branched and more spiny
      than those in primates.
AB  - Pyramidal cells are characterized by markedly different sized dendritic trees,
      branching patterns, and spine density across the cortical mantle. Moreover,
      pyramidal cells have been shown to differ in structure among homologous cortical
      areas in different species; however, most of these studies have been conducted in
      primates. Whilst pyramidal cells have been quantified in a few cortical areas in
      some other species there are, as yet, no uniform comparative data on pyramidal
      cell structure in a homologous cortical area among species in different Orders.
      Here we studied layer III pyramidal cells in V1 of three species of rodents, the
      greater cane rat, highveld gerbil, and four-striped mouse, by the same
      methodology used to sample data from layer III pyramidal cells in primates. The
      data reveal markedly different trends between rodents and primates: there is an
      appreciable increase in the size, branching complexity, and number of spines in
      the dendritic trees of pyramidal cells with increasing size of V1 in the brain in
      rodents, whereas there is relatively little difference in primates. Moreover,
      pyramidal cells in rodents are larger, more branched and more spinous than those
      in primates. For example, the dendritic trees of pyramidal cells in V1 of the
      adult cane rat are nearly three times larger, and have more than 10 times the
      number of spines in their basal dendritic trees, than those in V1 of the adult
      macaque (7900 and 600, respectively), which has a V1 40 times the size that of
      the cane rat. It remains to be determined to what extent these differences may
      result from development or reflect evolutionary and/or processing
      specializations. 

PMID- 24574980
TI  - Electrophysiological characterization of entopeduncular nucleus neurons in
      anesthetized and freely moving rats.
AB  - The EntoPeduncular nucleus (EP), which is homologous to the internal segment of
      the Globus Pallidus (GPi) in primates, is one of the two basal ganglia (BG)
      output nuclei. Despite their importance in cortico-BG information processing, EP
      neurons have rarely been investigated in rats and there is no available
      electrophysiological characterization of EP neurons in vivo. We recorded and
      analyzed the activity of EP neurons in freely moving as well as anesthetized
      rats, and compared their activity patterns. Examination of neuronal firing
      statistics during wakefulness suggested that similar to neurons recorded in the
      primate GPi, EP neurons are a single population characterized by Poisson-like
      firing. Under isoflurane anesthesia the firing rate of EP neurons decreased
      substantially and their coefficient of variation and relative duration of
      quiescence periods increased. Investigation of the relationship between firing
      rate and depth of anesthesia revealed two distinct neuronal groups: one that
      decreased its firing rate with the increase in anesthesia level, and a second
      group where the firing rate was independent of anesthesia level. Post-hoc
      examination of the firing properties of the two groups showed that they were
      statistically distinct. These results may thus help reconcile in vitro studies in
      rats and primates which have reported two distinct neuronal populations, and in
      vivo studies in behaving primates indicating one homogeneous population. Our data
      support the existence of two distinct neuronal populations in the rat EP that can
      be distinguished by their characteristic firing response to anesthesia. 

PMID- 24574981
TI  - Asymmetric pallidal neuronal activity in patients with cervical dystonia.
AB  - The origin of asymmetric clinical manifestation of symptoms in patients suffering
      from cervical dystonia (CD) is hitherto poorly understood. Dysregulated neuronal
      activity in the basal ganglia has been suggested to have a role in the
      pathophysiology of CD. Here, we re-assessed the question to what extent relative
      changes occur in the direct vs. indirect basal ganglia pathway in CD, whether
      these circuit changes are lateralized, and how these alterations relate to CD
      symptoms. To this end, we recorded ongoing single cell and local field potential
      (LFP) activity from the external (GPe) and internal pallidal segment (GPi) of 13
      CD patients undergoing microelectrode-guided stereotactic surgery for deep brain
      stimulation in the GPi. We compared pallidal recordings from CD patients operated
      under local anaesthesia (LA) with those obtained in CD patients operated under
      general anaesthesia (GA). In awake patients, mean GPe discharge rate (52 Hz) was
      lower than that of GPi (72 Hz). Mean GPi discharge ipsilateral to the side of
      head turning was higher than contralateral and correlated with torticollis
      symptom severity. Lateralized differences were absent at the level of the GPe and
      in recordings from patients operated under GA. Furthermore, in the GPi of CD
      patients there was a subpopulation of theta-oscillatory cells with unique
      bursting characteristics. Power and coherence of GPe- and GPi-LFPs were dominated
      by a theta peak and also exhibited band-specific interhemispheric differences.
      Strong cross-frequency coupling of low-gamma amplitude to theta phase was a
      feature of pallidal LFPs recorded under LA, but not GA. These results indicate
      that CD is associated with an asymmetric pallidal outflow. Based on the finding
      of symmetric neuronal discharges in the GPe, we propose that an imbalanced
      interhemispheric direct pathway gain may be involved in CD pathophysiology. 

PMID- 24574983
TI  - Habituation, sensitization, and Pavlovian conditioning.
AB  - In this brief review, I argue that the impact of a stimulus on behavioral control
      increase as the distance of the stimulus to the body decreases. Habituation,
      i.e., decrement in response intensity repetition of the triggering stimulus, is
      the default state for sensory processing, and the likelihood of habituation is
      higher for distal stimuli. Sensitization, i.e., increment in response intensity
      upon stimulus repetition, occurs in a state dependent manner for proximal stimuli
      that make direct contact with the body. In Pavlovian conditioning paradigms, the
      unconditioned stimulus (US) is always a more proximal stimulus than the
      conditioned stimulus (CS). The mechanisms of associative and non-associative
      learning are not independent. CS-US pairings lead to formation of associations if
      sensitizing modulation from a proximal US prevents the habituation for a distal
      anticipatory CS. 

PMID- 24574982
TI  - fMRI correlates of object-based attentional facilitation vs. suppression of
      irrelevant stimuli, dependent on global grouping and endogenous cueing.
AB  - Theories of object-based attention often make two assumptions: that attentional
      resources are facilitatory, and that they spread automatically within grouped
      objects. Consistent with this, ignored visual stimuli can be easier to process,
      or more distracting, when perceptually grouped with an attended target stimulus.
      But in past studies, the ignored stimuli often shared potentially relevant
      features or locations with the target. In this fMRI study, we measured the
      effects of attention and grouping on Blood Oxygenation Level Dependent (BOLD)
      responses in the human brain to entirely task-irrelevant events. Two
      checkerboards were displayed each in opposite hemifields, while participants
      responded to check-size changes in one pre-cued hemifield, which varied between
      blocks. Grouping (or segmentation) between hemifields was manipulated between
      blocks, using common (vs. distinct) motion cues. Task-irrelevant transient events
      were introduced by randomly changing the color of either checkerboard, attended
      or ignored, at unpredictable intervals. The above assumptions predict heightened
      BOLD signals for irrelevant events in attended vs. ignored hemifields for
      ungrouped contexts, but less such attentional modulation under grouping, due to
      automatic spreading of facilitation across hemifields. We found the opposite
      pattern, in primary visual cortex. For ungrouped stimuli, BOLD signals associated
      with task-irrelevant changes were lower, not higher, in the attended vs. ignored
      hemifield; furthermore, attentional modulation was not reduced but actually
      inverted under grouping, with higher signals for events in the attended vs.
      ignored hemifield. These results challenge two popular assumptions underlying
      object-based attention. We consider a broader biased-competition framework: task
      irrelevant stimuli are suppressed according to how strongly they compete with
      task-relevant stimuli, with intensified competition when the irrelevant features
      or locations comprise the same object. 

PMID- 24574986
TI  - Glucocorticoid receptor gene inactivation in dopamine-innervated areas
      selectively decreases behavioral responses to amphetamine.
AB  - The meso-cortico-limbic system, via dopamine release, encodes the rewarding and
      reinforcing properties of natural rewards. It is also activated in response to
      abused substances and is believed to support drug-related behaviors. Dysfunctions
      of this system lead to several psychiatric conditions including feeding disorders
      and drug addiction. These disorders are also largely influenced by environmental
      factors and in particular stress exposure. Stressors activate the corticotrope
      axis ultimately leading to glucocorticoid hormone (GCs) release. GCs bind the
      glucocorticoid receptor (GR) a transcription factor ubiquitously expressed
      including within the meso-cortico-limbic tract. While GR within dopamine
      innervated areas drives cocaine's behavioral responses, its implication in
      responses to other psychostimulants such as amphetamine has never been clearly
      established. Moreover, while extensive work has been made to uncover the role of
      this receptor in addicted behaviors, its contribution to the rewarding and
      reinforcing properties of food has yet to be investigated. Using mouse models
      carrying GR gene inactivation in either dopamine neurons or in dopamine
      innervated areas, we found that GR in dopamine responsive neurons is essential to
      properly build amphetamine-induced conditioned place preference and locomotor
      sensitization. c-Fos quantification in the nucleus accumbens further confirmed
      defective neuronal activation following amphetamine injection. These diminished
      neuronal and behavioral responses to amphetamine may involve alterations in
      glutamate transmission as suggested by the decreased MK801-elicited
      hyperlocomotion and by the hyporeactivity to glutamate of a subpopulation of
      medium spiny neurons. In contrast, GR inactivation did not affect rewarding and
      reinforcing properties of food suggesting that responding for natural reward
      under basal conditions is preserved in these mice. 

PMID- 24574985
TI  - Quantifying the sensory and emotional perception of touch: differences between
      glabrous and hairy skin.
AB  - The perception of touch is complex and there has been a lack of ways to describe
      the full tactile experience quantitatively. Guest et al. (2011) developed a Touch
      Perception Task (TPT) in order to capture such experiences, and here we used the
      TPT to examine differences in sensory and emotional aspects of touch at different
      skin sites. We compared touch on three skin sites: the hairy arm and cheek, and
      the glabrous palm. The hairy skin contains C-tactile (CT) afferents, which play a
      role in affective touch, whereas glabrous skin does not contain CT afferents and
      is involved in more discriminative touch. In healthy volunteers, three different
      materials (soft brush, sandpaper, fur) were stroked across these skin sites
      during self-touch or experimenter-applied touch. After each stimulus,
      participants rated the tactile experience using descriptors in the TPT. Sensory
      and emotional descriptors were analyzed using factor analyses. Five sensory
      factors were found: Texture, Pile, Moisture, Heat/Sharp and Cold/Slip, and three
      emotional factors: Positive Affect, Arousal, and Negative Affect. Significant
      differences were found in the use of descriptors in touch to hairy vs. glabrous
      skin: this was most evident in touch on forearm skin, which produced higher
      emotional content. The touch from another was also judged as more emotionally
      positive then self-touch, and participants readily discriminated between the
      materials on all factors. The TPT successfully probed sensory and emotional
      percepts of the touch experience, which aided in identifying skin where emotional
      touch was more pertinent. It also highlights the potentially important role for
      CTs in the affective processing of inter-personal touch, in combination with
      higher-order influences, such as through cultural belonging and previous
      experiences. 

PMID- 24574987
TI  - Chronic exposure to a gambling-like schedule of reward predictive stimuli can
      promote sensitization to amphetamine in rats.
AB  - Addiction is considered to be a brain disease caused by chronic exposure to
      drugs. Sensitization of brain dopamine (DA) systems partly mediates this effect.
      Pathological gambling (PG) is considered to be a behavioral addiction. Therefore,
      PG may be caused by chronic exposure to gambling. Identifying a gambling-induced
      sensitization of DA systems would support this possibility. Gambling rewards
      evoke DA release. One episode of slot machine play shifts the DA response from
      reward delivery to onset of cues (spinning reels) for reward, in line with
      temporal difference learning principles. Thus, conditioned stimuli (CS) play a
      key role in DA responses to gambling. In primates, DA response to a CS is
      strongest when reward probability is 50%. Under this schedule the CS elicits an
      expectancy of reward but provides no information about whether it will occur on a
      given trial. During gambling, a 50% schedule should elicit maximal DA release.
      This closely matches reward frequency (46%) on a commercial slot machine. DA
      release can contribute to sensitization, especially for amphetamine. Chronic
      exposure to a CS that predicts reward 50% of the time could mimic this effect. We
      tested this hypothesis in three studies with rats. Animals received 15 * 45-min
      exposures to a CS that predicted reward with a probability of 0, 25, 50, 75, or
      100%. The CS was a light; the reward was a 10% sucrose solution. After training,
      rats received a sensitizing regimen of five separate doses (1 mg/kg) of d
      amphetamine. Lastly they received a 0.5 or 1 mg/kg amphetamine challenge prior to
      a 90-min locomotor activity test. In all three studies the 50% group displayed
      greater activity than the other groups in response to both challenge doses.
      Effect sizes were modest but consistent, as reflected by a significant group *
      rank association (phi = 0.986, p = 0.025). Chronic exposure to a gambling-like
      schedule of reward predictive stimuli can promote sensitization to amphetamine
      much like exposure to amphetamine itself. 

PMID- 24574984
TI  - Nonhuman gamblers: lessons from rodents, primates, and robots.
AB  - The search for neuronal and psychological underpinnings of pathological gambling
      in humans would benefit from investigating related phenomena also outside of our
      species. In this paper, we present a survey of studies in three widely different
      populations of agents, namely rodents, non-human primates, and robots. Each of
      these populations offers valuable and complementary insights on the topic, as the
      literature demonstrates. In addition, we highlight the deep and complex
      connections between relevant results across these different areas of research
      (i.e., cognitive and computational neuroscience, neuroethology, cognitive
      primatology, neuropsychiatry, evolutionary robotics), to make the case for a
      greater degree of methodological integration in future studies on pathological
      gambling. 

PMID- 24574989
TI  - Assessing learning as a possible sign of consciousness in post-coma persons with
      minimal responsiveness.
AB  - A learning test procedure based on operant principles may be useful in the
      diagnosis (and eventually rehabilitation) of post-coma persons with minimal
      responsiveness. This study was aimed at extending the evaluation of such a
      procedure with seven participants who presented with very limited behavior and
      apparently severe disorders of consciousness. The procedure was evaluated through
      an ABACB design, in which A represented baseline phases without stimulation, B
      intervention phases with brief stimulation periods contingent on specific
      responses of the participants, and C a control phase in which stimulation was
      available all the time. Increased responding during the B phases, as opposed to
      the A and C phases, was taken to indicate learning and possibly a non-reflective
      expression of phenomenal consciousness. All participants were also evaluated with
      the coma recovery scale-revised (CRS-R) prior to the start of the learning test
      procedure and at the end of it. The results of the learning test showed that all
      participants had significantly higher responding levels during the B phases. The
      CRS-R scores suggested minimally conscious state for four of them prior to the
      learning test and for five of them after the completion of the learning test. The
      implications of the findings are discussed in terms of potential and time cost of
      the learning test. 

PMID- 24574991
TI  - Negative emotion modulates prefrontal cortex activity during a working memory
      task: a NIRS study.
AB  - This study investigated the neural processing underlying the cognitive control of
      emotions induced by the presentation of task-irrelevant emotional pictures before
      a working memory task. Previous studies have suggested that the cognitive control
      of emotion involves the prefrontal regions. Therefore, we measured the
      hemodynamic responses that occurred in the prefrontal region with a 16-channel
      near-infrared spectroscopy (NIRS) system. In our experiment, participants
      observed two negative or two neutral pictures in succession immediately before a
      1-back or 3-back task. Pictures were selected from the International Affective
      Picture System (IAPS). We measured the changes in the concentration of oxygenated
      hemoglobin (oxyHb) during picture presentation and during the n-back task. The
      emotional valence of the picture affected the oxyHb changes in anterior parts of
      the medial prefrontal cortex (MPFC) (located in the left and right superior
      frontal gyrus) and left inferior frontal gyrus during the n-back task; the oxyHb
      changes during the task were significantly greater following negative rather than
      neutral stimulation. As indicated in a number of previous studies, and the time
      courses of the oxyHb changes in our study, activation in these locations is
      possibly led by cognitive control of emotion, though we cannot deny it may simply
      be emotional responses. There were no effects of emotion on oxyHb changes during
      picture presentation or on n-back task performance. Although further studies are
      necessary to confirm this interpretation, our findings suggest that NIRS can be
      used to investigate neural processing during emotional control. 

PMID- 24574990
TI  - Spatial attention in written word perception.
AB  - The role of attention in visual word recognition and reading aloud is a long
      debated issue. Studies of both developmental and acquired reading disorders
      provide growing evidence that spatial attention is critically involved in word
      reading, in particular for the phonological decoding of unfamiliar letter
      strings. However, studies on healthy participants have produced contrasting
      results. The aim of this study was to investigate how the allocation of spatial
      attention may influence the perception of letter strings in skilled readers. High
      frequency words (HFWs), low frequency words and pseudowords were briefly and
      parafoveally presented either in the left or the right visual field. Attentional
      allocation was modulated by the presentation of a spatial cue before the target
      string. Accuracy in reporting the target string was modulated by the spatial cue
      but this effect varied with the type of string. For unfamiliar strings,
      processing was facilitated when attention was focused on the string location and
      hindered when it was diverted from the target. This finding is consistent the
      assumptions of the CDP+ model of reading aloud, as well as with familiarity
      sensitivity models that argue for a flexible use of attention according with the
      specific requirements of the string. Moreover, we found that processing of HFWs
      was facilitated by an extra-large focus of attention. The latter result is
      consistent with the hypothesis that a broad distribution of attention is the
      default mode during reading of familiar words because it might optimally engage
      the broad receptive fields of the highest detectors in the hierarchical system
      for visual word recognition. 

PMID- 24574988
TI  - Investigating habits: strategies, technologies and models.
AB  - Understanding habits at a biological level requires a combination of behavioral
      observations and measures of ongoing neural activity. Theoretical frameworks as
      well as definitions of habitual behaviors emerging from classic behavioral
      research have been enriched by new approaches taking account of the
      identification of brain regions and circuits related to habitual behavior.
      Together, this combination of experimental and theoretical work has provided key
      insights into how brain circuits underlying action-learning and action-selection
      are organized, and how a balance between behavioral flexibility and fixity is
      achieved. New methods to monitor and manipulate neural activity in real time are
      allowing us to have a first look "under the hood" of a habit as it is formed and
      expressed. Here we discuss ideas emerging from such approaches. We pay special
      attention to the unexpected findings that have arisen from our own experiments
      suggesting that habitual behaviors likely require the simultaneous activity of
      multiple distinct components, or operators, seen as responsible for the
      contrasting dynamics of neural activity in both cortico-limbic and sensorimotor
      circuits recorded concurrently during different stages of habit learning. The
      neural dynamics identified thus far do not fully meet expectations derived from
      traditional models of the structure of habits, and the behavioral measures of
      habits that we have made also are not fully aligned with these models. We explore
      these new clues as opportunities to refine an understanding of habits. 

PMID- 24574993
TI  - Systematic network lesioning reveals the core white matter scaffold of the human
      brain.
AB  - Brain connectivity loss due to traumatic brain injury, stroke or multiple
      sclerosis can have serious consequences on life quality and a measurable impact
      upon neural and cognitive function. Though brain network properties are known to
      be affected disproportionately by injuries to certain gray matter regions, the
      manner in which white matter (WM) insults affect such properties remains poorly
      understood. Here, network-theoretic analysis allows us to identify the existence
      of a macroscopic neural connectivity core in the adult human brain which is
      particularly sensitive to network lesioning. The systematic lesion analysis of
      brain connectivity matrices from diffusion neuroimaging over a large sample (N =
      110) reveals that the global vulnerability of brain networks can be predicated
      upon the extent to which injuries disrupt this connectivity core, which is found
      to be quite distinct from the set of connections between rich club nodes in the
      brain. Thus, in addition to connectivity within the rich club, the brain as a
      network also contains a distinct core scaffold of network edges consisting of WM
      connections whose damage dramatically lowers the integrative properties of brain
      networks. This pattern of core WM fasciculi whose injury results in major
      alterations to overall network integrity presents new avenues for clinical
      outcome prediction following brain injury by relating lesion locations to
      connectivity core disruption and implications for recovery. The findings of this
      study contribute substantially to current understanding of the human WM
      connectome, its sensitivity to injury, and clarify a long-standing debate
      regarding the relative prominence of gray vs. WM regions in the context of brain
      structure and connectomic architecture. 

PMID- 24574992
TI  - Technology-based intervention programs to promote stimulation control and
      communication in post-coma persons with different levels of disability.
AB  - Post-coma persons in a minimally conscious state and with extensive motor
      impairment or emerging/emerged from such a state, but affected by lack of speech
      and motor impairment, tend to be passive and isolated. A way to help them develop
      functional responding to control environmental events and communication involves
      the use of intervention programs relying on assistive technology. This paper
      provides an overview of technology-based intervention programs for enabling the
      participants to (a) access brief periods of stimulation through one or two
      microswitches, (b) pursue stimulation and social contact through the combination
      of a microswitch and a sensor connected to a speech generating device (SGD) or
      through two SGD-related sensors, (c) control stimulation options through computer
      or radio systems and a microswitch, (d) communicate through modified messaging or
      telephone systems operated via microswitch, and (e) control combinations of
      leisure and communication options through computer systems operated via
      microswitch. Twenty-six studies, involving a total of 52 participants, were
      included in this paper. The intervention programs were carried out using single
      subject methodology, and their outcomes were generally considered positive from
      the standpoint of the participants and their context. Practical implications of
      the programs are discussed. 

PMID- 24574994
TI  - Face identity matching is influenced by emotions conveyed by face and body.
AB  - Faces provide information about multiple characteristics like personal identity
      and emotion. Classical models of face perception postulate separate sub-systems
      for identity and expression recognition but recent studies have documented
      emotional contextual influences on recognition of faces. The present study
      reports three experiments where participants were presented realistic face-body
      compounds in a 2 category (face and body) * 2 emotion (neutral and fearful)
      factorial design. The task always consisted of two-alternative forced choice
      facial identity matching. The results show that during simultaneous face identity
      matching, the task irrelevant bodily expressions influence processing of facial
      identity, under conditions of unlimited viewing (Experiment 1) as well as during
      brief (750 ms) presentation (Experiment 2). In addition, delayed (5000 ms) face
      identity matching of rapidly (150 ms) presented face-body compounds, was also
      influenced by the body expression (Experiment 3). The results indicate that face
      identity perception mechanisms interact with processing of bodily and facial
      expressions. 

PMID- 24574995
TI  - Interhemispheric auditory connectivity: structure and function related to
      auditory verbal hallucinations.
AB  - Auditory verbal hallucinations (AVH) are one of the most common and most
      distressing symptoms of schizophrenia. Despite fundamental research, the
      underlying neurocognitive and neurobiological mechanisms are still a matter of
      debate. Previous studies suggested that "hearing voices" is associated with a
      number of factors including local deficits in the left auditory cortex and a
      disturbed connectivity of frontal and temporoparietal language-related areas. In
      addition, it is hypothesized that the interhemispheric pathways connecting right
      and left auditory cortices might be involved in the pathogenesis of AVH. Findings
      based on Diffusion-Tensor-Imaging (DTI) measurements revealed a remarkable
      interindividual variability in size and shape of the interhemispheric auditory
      pathways. Interestingly, schizophrenia patients suffering from AVH exhibited
      increased fractional anisotropy (FA) in the interhemispheric fibers than non
      hallucinating patients. Thus, higher FA-values indicate an increased severity of
      AVH. Moreover, a dichotic listening (DL) task showed that the interindividual
      variability in the interhemispheric auditory pathways was reflected in the
      behavioral outcome: stronger pathways supported a better information transfer and
      consequently improved speech perception. This detection indicates a specific
      structure-function relationship, which seems to be interindividually variable.
      This review focuses on recent findings concerning the structure-function
      relationship of the interhemispheric pathways in controls, hallucinating and non
      hallucinating schizophrenia patients and concludes that changes in the structural
      and functional connectivity of auditory areas are involved in the pathophysiology
      of AVH. 

PMID- 24574996
TI  - The focus of attention is similar to other memory systems rather than uniquely
      different.
AB  - According to some current theories, the focus of attention (FOA), part of working
      memory, represents items in a privileged state that is more accessible than items
      stored in other memory systems. One line of evidence supporting the distinction
      between the FOA and other memory systems is the finding that items in the FOA are
      immune to proactive interference (when something learned earlier impairs the
      ability to remember something learned more recently). The FOA, then, is held to
      be unique: it is the only memory system that is not susceptible to proactive
      interference. We review the literature used to support this claim, and although
      there are many studies in which proactive interference was not observed, we found
      more studies in which it was observed. We conclude that the FOA is not immune to
      proactive interference: items in the FOA are susceptible to proactive
      interference just like items in every other memory system. And, just as in all
      other memory systems, it is how the items are represented and processed that
      plays a critical role in determining whether proactive interference will be
      observed. 

PMID- 24574997
TI  - Mathematical learning difficulties subtypes classification.

PMID- 24574998
TI  - Decoding individual natural scene representations during perception and imagery.
AB  - We used a multi-voxel classification analysis of functional magnetic resonance
      imaging (fMRI) data to determine to what extent item-specific information about
      complex natural scenes is represented in several category-selective areas of
      human extrastriate visual cortex during visual perception and visual mental
      imagery. Participants in the scanner either viewed or were instructed to
      visualize previously memorized natural scene exemplars, and the neuroimaging data
      were subsequently subjected to a multi-voxel pattern analysis (MVPA) using a
      support vector machine (SVM) classifier. We found that item-specific information
      was represented in multiple scene-selective areas: the occipital place area
      (OPA), parahippocampal place area (PPA), retrosplenial cortex (RSC), and a scene
      selective portion of the precuneus/intraparietal sulcus region (PCu/IPS).
      Furthermore, item-specific information from perceived scenes was re-instantiated
      during mental imagery of the same scenes. These results support findings from
      previous decoding analyses for other types of visual information and/or brain
      areas during imagery or working memory, and extend them to the case of visual
      scenes (and scene-selective cortex). Taken together, such findings support models
      suggesting that reflective mental processes are subserved by the re-instantiation
      of perceptual information in high-level visual cortex. We also examined activity
      in the fusiform face area (FFA) and found that it, too, contained significant
      item-specific scene information during perception, but not during mental imagery.
      This suggests that although decodable scene-relevant activity occurs in FFA
      during perception, FFA activity may not be a necessary (or even relevant)
      component of one's mental representation of visual scenes. 

PMID- 24575000
TI  - Voluntary Out-of-Body Experience: An fMRI Study.
AB  - The present single-case study examined functional brain imaging patterns in a
      participant that reported being able, at will, to produce somatosensory
      sensations that are experienced as her body moving outside the boundaries of her
      physical body all the while remaining aware of her unmoving physical body. We
      found that the brain functional changes associated with the reported extra
      corporeal experience (ECE) were different than those observed in motor imagery.
      Activations were mainly left-sided and involved the left supplementary motor area
      and supramarginal and posterior superior temporal gyri, the last two overlapping
      with the temporal parietal junction that has been associated with out-of-body
      experiences. The cerebellum also showed activation that is consistent with the
      participant's report of the impression of movement during the ECE. There was also
      left middle and superior orbital frontal gyri activity, regions often associated
      with action monitoring. The results suggest that the ECE reported here represents
      an unusual type of kinesthetic imagery. 

PMID- 24575001
TI  - Algorithms for the analysis of ensemble neural spiking activity using
      simultaneous-event multivariate point-process models.
AB  - Understanding how ensembles of neurons represent and transmit information in the
      patterns of their joint spiking activity is a fundamental question in
      computational neuroscience. At present, analyses of spiking activity from
      neuronal ensembles are limited because multivariate point process (MPP) models
      cannot represent simultaneous occurrences of spike events at an arbitrarily small
      time resolution. Solo recently reported a simultaneous-event multivariate point
      process (SEMPP) model to correct this key limitation. In this paper, we show how
      Solo's discrete-time formulation of the SEMPP model can be efficiently fit to
      ensemble neural spiking activity using a multinomial generalized linear model
      (mGLM). Unlike existing approximate procedures for fitting the discrete-time
      SEMPP model, the mGLM is an exact algorithm. The MPP time-rescaling theorem can
      be used to assess model goodness-of-fit. We also derive a new marked point
      process (MkPP) representation of the SEMPP model that leads to new thinning and
      time-rescaling algorithms for simulating an SEMPP stochastic process. These
      algorithms are much simpler than multivariate extensions of algorithms for
      simulating a univariate point process, and could not be arrived at without the
      MkPP representation. We illustrate the versatility of the SEMPP model by
      analyzing neural spiking activity from pairs of simultaneously-recorded rat
      thalamic neurons stimulated by periodic whisker deflections, and by simulating
      SEMPP data. In the data analysis example, the SEMPP model demonstrates that
      whisker motion significantly modulates simultaneous spiking activity at the 1 ms
      time scale and that the stimulus effect is more than one order of magnitude
      greater for simultaneous activity compared with non-simultaneous activity.
      Together, the mGLM, the MPP time-rescaling theorem and the MkPP representation of
      the SEMPP model offer a theoretically sound, practical tool for measuring joint
      spiking propensity in a neuronal ensemble. 

PMID- 24575002
TI  - When "I" becomes "We": ethical implications of emerging brain-to-brain
      interfacing technologies.

PMID- 24575003
TI  - Successful Treatment of Congenital Lymphangioma Circumscriptum of the Vulva with
      CO2 and Long-Pulsed Nd:YAG Lasers.
AB  - A 16-year-old girl presented with a 9-year history of vesicles on the vulva. She
      had initially taken a wait-and-see approach, but required treatment because of
      bleeding. Histological examination of a biopsied vesicle revealed dilated lymph
      channels in the upper dermis, suggesting lymphangioma circumscriptum (LC). The
      challenge for this pathology has been to find a conservative treatment with low
      morbidity and better results than those reported for surgical excision, which has
      been the mainstay of therapy. In this case, LC of the vulva was successfully
      treated using a 10,600-nm CO2 laser and long-pulsed Nd:YAG laser. Use of the
      10,600-nm CO2 laser and long-pulsed Nd:YAG laser appeared effective for treating
      LC. 

PMID- 24574999
TI  - Clinical application of spatiotemporal distributed source analysis in presurgical
      evaluation of epilepsy.
AB  - Magnetoencephalography (MEG), which acquires neuromagnetic fields in the brain,
      is a useful diagnostic tool in presurgical evaluation of epilepsy. Previous
      studies have shown that MEG affects the planning intracranial
      electroencephalography placement and correlates with surgical outcomes by using a
      single dipole model. Spatiotemporal source analysis using distributed source
      models is an advanced method for analyzing MEG, and has been recently introduced
      for analyzing epileptic spikes. It has advantages over the conventional single
      dipole analysis for obtaining accurate sources and understanding the propagation
      of epileptic spikes. In this article, we review the source analysis methods,
      describe the techniques of the distributed source analysis, interpretation of
      source distribution maps, and discuss the benefits and feasibility of this method
      in evaluation of epilepsy. 

PMID- 24575004
TI  - Concurrent reactivation of herpes simplex and varicella zoster viruses confirmed
      by the loop-mediated isothermal amplification assay.
AB  - Concurrent reactivation of herpes simplex and varicella zoster viruses is rare.
      Here, we describe the case of an elderly patient with herpes labialis and herpes
      zoster manifesting as a right-side facial eruption with vesicles and crusting.
      The loop-mediated isothermal amplification (LAMP) assay demonstrated the presence
      of both herpes simplex virus type 1 and varicella zoster virus in swab samples
      taken from the face, which was confirmed by real-time PCR, suggesting concurrent
      reactivation of both viruses. The use of the LAMP assay in the present case
      indicates its usefulness in the diagnosis of atypical herpes infections. 

PMID- 24575005
TI  - Acquired ichthyosis triggered by an osseous hemangiopericytoma: a case report and
      review of the literature.
AB  - Ichthyoses are a heterogeneous group of cutaneous keratinization disorders that
      can be congenital or acquired. Apart from neoplastic disorders, the acquired form
      of ichthyosis (AI) has been associated with a variety of diseases including
      infections, autoimmune/inflammatory and endocrine/metabolic diseases as well as
      nutritional conditions, medications and others. However, malignancy accounts for
      half of the reported cases, most commonly including lymphoproliferative
      disorders. We present a case of AI as a paraneoplastic skin manifestation of a
      primary, osseous hemangiopericytoma (HP) accompanied by multiple liver
      metastases. We also review the literature and discuss the necessity of
      investigating underlying diseases, especially malignancy, when adult-onset
      ichthyosis arises. 

PMID- 24575006
TI  - Malignant melanoma with probable smooth muscle differentiation.
AB  - Malignant melanomas occasionally exhibit various divergent differentiation types.
      Of these, smooth muscle differentiation is extremely rare; only 1 case has been
      reported in the literature until recently. We report an extremely rare case of
      malignant melanoma with smooth muscle differentiation, which appeared as an
      amelanotic reddish nodule on the left toe. 

PMID- 24575007
TI  - Unmasking Cryptococcal Meningitis Immune Reconstitution Inflammatory Syndrome due
      to Granulocyte Colony-Stimulating Factor Use in a Patient with a Poorly
      Differentiated Germ Cell Neoplasm.
AB  - Cryptococcal meningitis immune reconstitution inflammatory syndrome (IRIS) is
      frequently seen in patients with HIV and less frequently in patients on immune
      suppressive medications for other conditions. Here, we describe the first
      reported case of unmasking cryptococcal IRIS due to granulocyte colony
      stimulating factor used in an HIV-negative patient with chemotherapy-induced
      neutropenia. 

PMID- 24575008
TI  - Primary synovial sarcoma of the thyroid gland: case report and review of the
      literature.
AB  - Synovial sarcoma (SVS) of the thyroid gland is exceedingly rare. We report the
      case of a 55-year-old man with a rapidly growing 7-cm neck mass. Because of
      suspicion of anaplastic thyroid carcinoma, a total thyroidectomy was planned,
      without preoperative cytology. During surgery, the tumor ruptured, leading to
      fragmented and incomplete resection. The morphological and immunohistochemical
      aspects suggested thyroid SVS, which was confirmed by fluorescent in situ
      hybridization (SYT gene rearrangement). The patient experienced immediate local
      relapse in close contact with large vessels and the thyroid cartilage and was
      referred to our institution. Doxorubicin-ifosfamide chemotherapy led to a minor
      response that authorized secondary conservative surgery. Because of
      microscopically incomplete resection, adjuvant radiotherapy was chosen and is
      ongoing 10 months after initial surgery. The prognosis of thyroid SVS is
      associated with a high risk for local and metastatic relapses. Pretreatment
      diagnosis is fundamental and may benefit from molecular analysis. Margin-free
      monobloc surgical excision is the best chance for cure, but adjuvant chemotherapy
      and radiotherapy deserve to be discussed. 

PMID- 24575009
TI  - nab-Paclitaxel in Combination with Carboplatin for a Previously Treated Thymic
      Carcinoma.
AB  - We present the case of a 40-year-old man with previously treated thymic
      carcinoma, complaining of gradually worsening back pain. Computed tomography
      scans of the chest showed multiple pleural disseminated nodules with a pleural
      effusion in the right thorax. The patient was treated with carboplatin on day 1
      plus nab-paclitaxel on day 1 and 8 in cycles repeated every 4 weeks. Objective
      tumor shrinkage was observed after 4 cycles of this regimen. In addition, the
      elevated serum cytokeratin 19 fragment level decreased, and the patient's back
      pain was relieved without any analgesics. Although he experienced grade 4
      neutropenia and granulocyte colony-stimulating factor (G-CSF) injection, the
      severity of thrombocytopenia and nonhematological toxicities such as reversible
      neuropathy did not exceed grade 1 during the treatment. To our knowledge, this is
      the first report to demonstrate the efficacy of combination chemotherapy
      consisting of carboplatin and nab-paclitaxel against thymic carcinoma. This case
      report suggests that nab-paclitaxel in combination with carboplatin can be a
      favorable chemotherapy regimen for advanced thymic carcinoma. 

PMID- 24575010
TI  - Stereotactic body radiation therapy as a bridge to transplantation and for
      recurrent disease in the transplanted liver of a patient with hepatocellular
      carcinoma.
AB  - Hepatocellular carcinoma (HCC) is one of the most common causes of cancer
      mortality worldwide. Despite orthotopic liver transplantation (OLT), recurrent
      HCC is a major cause of morbidity. In this case report, we evaluate the efficacy
      of stereotactic body radiation therapy (SBRT) as a bridge to OLT and for
      recurrence in the transplanted liver of a patient with HCC. A 52-year-old male
      with a history of chronic hepatitis C presented with a 1.7-cm liver lesion
      radiographically consistent with HCC, which was subsequently treated with a
      course of SBRT to 50 Gy in 5 fractions followed by OLT in 2009. The patient had a
      2.2-cm recurrence in the transplanted liver in 2012, which was treated with SBRT
      to 62.5 Gy in 5 fractions. He tolerated the course of radiotherapy well with no
      significant radiation-related toxicity and remains in complete remission
      approximately 1 year after SBRT. SBRT is a safe and effective modality for the
      treatment of recurrent HCC in the transplanted liver of the same patient
      initially treated with SBRT as a bridge to OLT. 

PMID- 24575012
TI  - Unilateral Optic Disc Papilloedema following Administration of Carboplatin
      Chemotherapy for Ovarian Carcinoma.
AB  - A 48-year-old woman with a positive BRCA1 gene mutation was diagnosed with stage
      3b high-grade ovarian endometrioid carcinoma. She was treated with adjuvant
      carboplatin at a dose of 740 mg (AUC 6) in 3-weekly cycles. Five days after her
      fifth cycle of carboplatin, she awoke with new-onset blurred vision in her left
      eye. An ophthalmology review showed left-sided disc oedema with normal optic
      nerve function tests and 6/24 visual acuity. A CT scan of the head and orbits was
      performed which showed no evidence of metastasis or raised intracranial pressure.
      An autoimmune screen was performed which did not reveal any explanation for her
      visual symptoms. Fundus fluorescein angiography showed bilateral intense late
      disc leakage with no evidence of vasculitis. Her chemotherapy was stopped in view
      of a radiological and biochemical remission and her visual symptoms were
      monitored. She was also started on a tapering dose of prednisolone 40 mg daily.
      Five months after the initial review, she has developed left optic disc atrophy
      with 6/18 visual acuity, while the right eye remains asymptomatic. The diagnosis
      was felt to be that of carboplatin-induced unilateral disc oedema, a very rare
      side effect of this chemotherapy. 

PMID- 24575011
TI  - Chemotherapy and surgical approach with repeated endovascular embolizations: safe
      interdisciplinary treatment for kasabach-merritt syndrome in a small baby.
AB  - INTRODUCTION: Kasabach-Merritt syndrome (KMS) is a life-threatening disease. We
      describe a combined medical and multistep, endovascular embolization that was
      successfully performed with surgery. CASE REPORT: A 40-day-old female baby was
      referred because of an infiltrating pelvic mass. Blood tests showed severe anemia
      and thrombocytopenia with consumptive coagulopathy. The clinical aspect was
      pathognomonic for KMS. Administration of steroids and chemotherapy were started
      and coagulation parameters were normalized with tumor volume regression. Three
      months later, elective surgical treatment became possible, and dissection and
      ligature of the left internal iliac artery and sacral artery were performed. The
      main arterial supply of the mass was embolized with Spongostan(r). Two months
      later, a second hybrid approach was adopted for embolization of the main vascular
      supply of the tumor occupying the left thigh. Via a third contralateral hybrid
      femoral approach and under fluoroscopy, selective catheterization of the left
      profunda femoris artery was performed. The arterial feeder of the tumor,
      localized at the left gluteus, was seen on a CT scan 2 months later and was
      embolized with Onyx-18. CONCLUSION: Chemotherapy and a tailored hybrid approach
      comprising repeated endovascular embolizations seem to be a safe treatment in
      cases of unresectable and life-threatening tumors in small babies.

PMID- 24575013
TI  - Carcinomatous myelitis and meningitis after a squamous cell carcinoma of the lip.
AB  - BACKGROUND: Nervous central system metastases from head and neck squamous cell
      carcinoma (SCC) are rare. We report an exceptional case of isolated
      leptomeningeal and spinal cord involvement few years after the diagnosis of
      invasive SCC of the lip. CASE REPORT: A 33-year-old man with a history of
      infracentimetric carcinoma of the lip developed back pain associated with
      progressive neurological disorders leading to paraplegia. This atypical
      presentation led to initial misdiagnosis, but radiological and cytological
      explorations finally confirmed the diagnosis of leptomeningeal and intramedullar
      secondary spinal cord lesions from his previously treated head and neck SCC.
      Systemic targeted therapy with epidermal growth factor receptor inhibitor and
      intrathecal chemotherapy led to prolonged disease stabilization. CONCLUSION: To
      our knowledge, this is the first case of isolated neurological metastases from a
      head and neck SCC. Combination of systemic targeted therapy and intrathecal
      chemotherapy may be effective in such cases.

PMID- 24575014
TI  - A case of pulmonary infiltrates in a patient with colon carcinoma.
AB  - A 31-year-old white male with a known history of colon carcinoma was referred to
      the Interventional Pulmonary service for right lower lobe infiltrates and mucous
      plugging on computed tomography with concern for pneumonia. Bronchoscopy was
      performed revealing a broad based mass completely obstructing the bronchus
      intermedius. It was possible to pass a probe into the right lower lobe, and
      subsequent photoablation and mechanical debulking revealed that the mass was
      arising near the origin of the superior basal segment of the right lower lobe
      (RB6) and could be resected. Pathology confirmed this was consistent with the
      patient's known primary colon carcinoma. The potential for endobronchial
      metastasis in patients with colorectal carcinoma should be investigated in those
      patients with new or worsening pulmonary symptoms and signs. 

PMID- 24575015
TI  - The use of lanreotide autogel(r) in the treatment of intestinal obstruction in a
      patient with adenocarcinoma.
AB  - Intestinal obstruction is a common complication in patients with advanced
      abdominal or pelvic cancer. The synthetic somatostatin analogue octreotide can
      help relieve nausea, vomiting and pain in patients with inoperable obstruction.
      Here, we report a case of recurrent intestinal obstruction in a patient with
      adenocarcinoma. Although the obstruction was resolved after 3 days of treatment
      with octreotide, new episodes of obstruction occurred, resulting in a delay of
      the chemotherapy treatment. After 3 episodes of obstruction, we initiated
      treatment with a longer-acting somatostatin analogue, lanreotide Autogel(r) 120
      mg, administered once every 4 weeks. The treatment with lanreotide Autogel is
      being continued, allowing for continuation of the chemotherapy without further
      episodes of intestinal subocclusion or obstruction. Until November 2013, the
      patient received eighteen 4-weekly injections of lanreotide Autogel and did not
      report side effects. This case report demonstrates the successful treatment of
      intestinal obstruction with lanreotide Autogel in a patient with adenocarcinoma. 

PMID- 24575016
TI  - A case of a giant growing serous cystic neoplasm of the pancreas.
AB  - Because of the widespread use of diagnostic imaging in recent years, serous
      cystic neoplasm (SCN) of the pancreas can often be detected even when small in
      diameter. SCNs are usually benign, but it is important to differentiate them from
      other types of cystic tumors. We report a case of a giant growing SCN that posed
      a challenge in differential diagnosis. 

PMID- 24575018
TI  - Intraperitoneal Paclitaxel is useful as adjuvant chemotherapy for advanced
      gastric cancer with serosal exposure.
AB  - BACKGROUND: Intraperitoneal administration of paclitaxel (PTX) can elicit a
      marked clinical response in peritoneal metastases of gastric cancer. METHODS: In
      this study, we retrospectively analyzed the clinical outcome of 17 patients who
      underwent R0 resection with D2 dissection for advanced gastric cancer with
      macroscopic serosal exposure and received intraperitoneal PTX as adjuvant
      therapy. RESULTS: A pathological study revealed that the depth of invasion of the
      primary tumor was pT4a or pT4b in 10 cases, and that the pN stage was more than
      pN2 in 8 cases. Genetic analysis of peritoneal lavage fluid was performed in 14
      cases, all of which were positive for carcinoembryonic antigen mRNA. In these
      patients, PTX was intraperitoneally administered at 20-60 mg/m(2) with oral S-1
      for 3-36 months after surgery. In a median follow-up period of 66 months,
      recurrence occurred in the liver and peritoneum in 2 (11.7%) and 1 (5.9%)
      patients, respectively, and no nodal recurrence was observed. Five-year overall
      survival and disease-free survival were 88.2 and 82.3%, respectively. CONCLUSION:
      Since these patients are considered to be a high-risk group for peritoneal
      recurrence, this result strongly suggests that adjuvant chemotherapy including
      intraperitoneal PTX is a promising protocol to improve the outcome of patients
      with advanced gastric cancer with serosal exposure.

PMID- 24575019
TI  - Successful Concurrent Chemoradiotherapy with Cisplatin plus Vinorelbine for
      Locally Advanced Thymic Carcinoma.
AB  - Little information is available about the usefulness of concurrent
      chemoradiotherapy for locally advanced thymic carcinoma due to a rare anterior
      mediastinal tumor. We experienced a case of locally advanced thymic carcinoma
      that responded well to concurrent thoracic radiotherapy combined with cisplatin
      plus vinorelbine chemotherapy. The patient showed remarkable tumor regression and
      has remained disease free for over 4 years following combined therapy. Concurrent
      chemoradiotherapy seems to be effective for locally advanced thymic carcinoma,
      and cisplatin plus vinorelbine could be an alternative chemotherapy regimen in
      combination with thoracic radiotherapy in patients with thymic carcinoma. 

PMID- 24575017
TI  - Metastatic Cancer of Cowper's Gland: A Rare Cancer Managed Successfully by
      Molecular Profiling.
AB  - Cancer of Cowper's gland is a very rare cancer. This case represents the 9th case
      in the medical literature. As such, there are no phase II or phase III trials to
      guide treatment. In this article, we report the successful treatment of a patient
      over a 7-year period guided solely by molecular profiling. Through multiple
      cycles to treatment, the cancer was controlled using drugs targeting c-kit, as
      the cancer steadily increased the expression of c-kit. This report also documents
      the use of a novel drug combination based on sunitinib that was well tolerated
      and may warrant testing in other c-kit-dependent cancers. 

PMID- 24575020
TI  - Primitive neuroectodermal tumor in an ovarian cystic teratoma: natural killer and
      neuroblastoma cell analysis.
AB  - In the present study, we report an extremely rare case of a 31-year-old woman
      with neuroblastoma arising in an ovarian cystic teratoma. We analyzed the
      expression of activating receptors on natural killer (NK) cells derived from the
      patient's peripheral blood and peritoneal fluid. In addition, we investigated the
      presence of specific ligands recognized by different NK cell receptors on tumor
      cells. We show that NK cells isolated from peritoneal fluid expressed certain
      triggering receptors including DNAM-1 (CD226) and CD16 with lower intensity as
      compared to peripheral blood NK cells. Remarkably, at variance with most cases of
      childhood neuroblastoma, the tumor cells from this patient expressed substantial
      amounts of HLA class-I molecules. These molecules are known to be protective
      against NK cell-mediated lysis. In addition, neuroblastoma cells expressed B7-H3
      (CD276), another surface molecule that inhibits NK cell function. Finally, this
      tumor did not express the PVR (CD155) and nectin-2 (CD112) ligands for the DNAM-1
      activating NK receptor, which plays a crucial role in NK/neuroblastoma
      interactions. Altogether, these findings indicate that the neuroblastoma cells of
      this patient express an NK-resistant surface phenotype, which is at least in part
      similar to that previously described in a fraction of childhood neuroblastoma. 

PMID- 24575021
TI  - Two Case Reports of Resensitization to Previous Chemotherapy with the Novel
      Hypoxia-Activated Hypomethylating Anticancer Agent RRx-001 in Metastatic
      Colorectal Cancer Patients.
AB  - The development of chemoresistance is a persistent problem during the treatment
      of cancer. Although reversion or modification of acquired chemoresistance has
      been previously observed, no systematic exploration has been undertaken. Here, we
      report a case study of 2 male patients, 62 and 66 years old, both with
      histologically proven, radiologically progressing, extensively pretreated,
      metastatic and refractory (>=2 conventional regimens and drug therapy) colorectal
      adenocarcinoma that was previously treated with FOLFIRI. The patients were
      resensitized to FOLFIRI after exposure to RRx-001 in the context of a phase-1
      study. RRx-001 is a novel, hypomethylating and free-radical-inducing anticancer
      agent that activates nitrite reduction to NO under hypoxia and has an impact on
      epigenetic pathways. The repression of DNA methyltransferase 1 by RRx-001 may
      lead to demethylation and reexpression of silenced tumor suppressor genes,
      leading to resensitization. These examples provide insight into a nascent
      strategy to improve the prognosis in heavily pretreated cancer patients and
      suggest routes for further exploration. 

PMID- 24575022
TI  - Subglottic chondrosarcoma presenting only mild acute-onset dyspnea: a case report
      and review of the literature.
AB  - Chondrosarcoma is categorized as a malignant cartilaginous tumor, which occurs
      rarely in the craniofacial region. We report the case of a 68-year-old man with
      chondrosarcoma in the subglottic area. His chief symptoms were hoarseness and
      mild dysphagia. A computed tomography scan revealed a lesion with expansion of
      the cricoid cartilage and marked reduction of the airway. After biopsy,
      histological inspection showed that chondrocytes are multi-nucleus, their size
      does not differ much and mitosis is not obvious. These are all characteristics of
      a low-grade chondrosarcoma. We performed an organ-preserving operation by
      debulking the low-grade malignant tumor in order to keep a patent airway. No
      further metastasis or airway compromise was evident during the 1-year follow-up
      visit. 

PMID- 24575023
TI  - Aggressive gastric carcinoma producing alpha-fetoprotein: a case report and
      review of the literature.
AB  - A 65-year-old man presented to our hospital with abdominal pain, dyspepsia and
      anorexia. Laboratory tests showed an altered liver function and abdomen
      ultrasonography revealed multiple liver nodules, suspected to be metastatic
      lesions. Serous tumor markers were elevated and a very high level of alpha
      fetoprotein was found. Computer tomography confirmed the hepatic lesions and
      disclosed a thickening of the lesser curvature of the gastric wall. A subsequent
      endoscopy showed an ulcer on the lesser curvature. Biopsies taken from the
      gastric ulcer and the liver nodule revealed an adenocarcinoma, both of gastric
      origin. Shortly after the diagnosis, the patient's condition worsened and he died
      only 15 days later. This case report illustrates how alpha-fetoprotein-producing
      gastric adenocarcinomas have a high incidence of venous and lymphatic invasion
      and a rapid hepatic spread with a very poor prognosis. 

PMID- 24575024
TI  - Sustained complete response after maintenance therapy with topotecan and
      erlotinib for recurrent cervical cancer with distant metastases.
AB  - INTRODUCTION: Recurrent cervical cancer is associated with a poor prognosis. Most
      treatment responses are partial and of short duration. The development of new
      therapies is vital to improve treatment for recurrent disease. Epidermal growth
      factor receptor (EGFR) inhibitors may have a role in this setting. CASE
      DESCRIPTION: A 53-year-old woman with stage IB2 squamous cell carcinoma of the
      cervix was initially treated with chemoradiation. Six months after completing
      treatment, she developed a recurrence in the common iliac and para-aortic lymph
      nodes above the previous radiation field and was treated with additional
      radiation therapy. Two years later, she developed recurrent disease in the left
      supraclavicular lymph nodes and was treated with chemoradiation followed by 3
      cycles of adjuvant cisplatin and topotecan. She had a complete response and was
      placed on maintenance therapy with topotecan and erlotinib, which was well
      tolerated and produced minimal side effects. After 20 months of maintenance
      therapy, it was discontinued given the long interval without evidence of disease.
      The patient is currently without evidence of disease 5 years after completing the
      topotecan-erlotinib treatment. CONCLUSION: We noted a sustained response in a
      patient with recurrent metastatic cervical cancer treated with radiotherapy,
      cisplatin, and topotecan followed by maintenance therapy with topotecan and
      erlotinib. Further evaluation of the role of EGFR inhibitors in this setting
      should be considered given their favorable toxicity profile and biological
      relevance.

PMID- 24575026
TI  - Trigeminal neuralgia as the first clinical manifestation of anti-hu
      paraneoplastic syndrome induced by a borderline ovarian mucinous tumor.
AB  - Paraneoplastic neurologic syndrome (PNS) is an uncommon manifestation of cancer
      that is not caused by the tumor or metastasis. Trigeminal neuralgia (TN) is an
      initial symptom of this disease, but it has rarely been reported in the
      literature. Here, we report the case of a 76-year-old woman who presented with
      classic TN, followed by limbic encephalitis due to an underlying ovarian
      intestinal-type mucinous borderline tumor, with the presence of anti-Hu
      antibodies. She recovered quickly after removal of the tumor and was essentially
      free of symptoms 2 weeks after surgery. Because PNS precedes the tumor in
      approximately 60% of cases, its rapid detection and treatment are crucial.
      Therefore, we propose that PNS be considered during the management of TN when
      brain imaging is normal, as it is followed by other central and/or peripheral
      neurological manifestations as well as the presence of systemic symptoms such as
      anemia, fatigability, loss of appetite, or weight loss. 

PMID- 24575025
TI  - Essential Tremor in a Charcot-Marie-Tooth Type 2C Kindred Does Not Segregate with
      the TRPV4 R269H Mutation.
AB  - BACKGROUND: We investigated 4 members of a family with type 2C Charcot-Marie
      Tooth (CMT) and self-reported essential tremor (ET). A heterozygous missense
      mutation, R269H, in the TRPV4 gene was previously reported in this family. Our
      genotypic data provided a rare opportunity to determine the etiology of the
      tremor. METHODS: Family study; the 4 tremor cases underwent a detailed
      neurological assessment. RESULTS: The clinical diagnosis of ET was confirmed in
      all 4 tremor cases based on stringent published research criteria. Two of these
      also had CMT. We genotyped all 4 family members for the TRPV4 R269H mutation. We
      confirmed the presence of the TRPV4 R269H mutation in the 2 family members with
      ET and CMT; however, the TRPV4 R269H mutation did not segregate with ET in the
      same family. CONCLUSIONS: In this particular CMT family, the tremor was
      clinically attributed to ET. Furthermore, genotype data indicated that the tremor
      was unlikely to be caused by incomplete penetrance or variable expressivity of
      the TRPV4 R269H mutation. Hence, the tremor likely represents ET. This
      establishes that in some CMT families the tremor diathesis likely represents a
      second disorder, namely ET.

PMID- 24575027
TI  - Caudal cingulate infarction manifesting astasia.
AB  - INTRODUCTION: Astasia is a rare presenting symptom of stroke, usually known as
      'thalamic astasia', induced by a lesion in the ventrolateral thalamus. We report
      a case of caudal cingulate infarction manifesting astasia. CASE PRESENTATION: A
      58-year-old male presented with inability to sit, stand and walk (astasia). No
      apparent motor weakness was noticed in the extremities. MRI revealed cerebral
      infarction in the caudal cingulate gyrus, which was located between the vertical
      commissure anterior (VCA) line and vertical commissure posterior (VPC) line. His
      symptoms persisted for 1 year to a lesser degree. CONCLUSION: Lesions in the
      caudal cingulate gyrus can present with astasia. The responsible lesion is
      located in the cingulate gyrus between the VCA and VPC line, which might
      correspond to the caudal cingulate zone in humans. We should keep in mind that
      astasia can be a presenting symptom of stroke.

PMID- 24575028
TI  - A Family with Mental Retardation, Epilepsy and Cerebellar Hypoplasia Showing
      Linkage to Chromosome 20p11.21-q11.23.
AB  - BACKGROUND: Cerebellar hypoplasia (CH) is a rare malformation caused by various
      etiologies, usually manifesting clinically as nonprogressive cerebellar ataxia
      with or without mental retardation. The molecular pathogenesis of the autosomal
      recessive cerebellar ataxias has a wide range of mechanisms. Differential
      diagnosis and categorization of the recessive cerebellar ataxias, however, need
      more specific, biochemical and genetic investigation. METHODS: This study applied
      whole-genome linkage analysis to study a family with nonprogressive cerebellar
      ataxia and additional mental retardation, epilepsy, and facial dysmorphic
      features. Genotyping and linkage analysis was done using the GeneChip Mapping
      250K NspI Array (Affymetrix Inc., Santa Clara, Calif., USA) for genome-wide
      linkage analysis of the genotyping data from the affected children and their
      parents. RESULTS: Allegro software version 1.2 was used for multipoint linkage
      analysis. We assumed an autosomal recessive inheritance pattern and assigned a
      penetrance of 0.999. Single-nucleotide polymorphism allele frequencies were
      estimated from the Affymetrix data of the Caucasian family studied. Using these
      parameters, a theoretical maximum logarithm of the odds score of 2.69 was
      identified at chromosome 20p11.21-q11.23. CONCLUSIONS: This chromosomal locus is
      unprecedented in autosomal recessive and nonprogressive ataxia disorder. Further
      investigation might reveal a new causative gene generating the CH phenotype.

PMID- 24575030
TI  - Brain dopamine transporter binding and glucose metabolism in progressive
      supranuclear palsy-like creutzfeldt-jakob disease.
AB  - Here, we present a patient with Creutzfeldt-Jakob disease (CJD) who developed
      initial symptoms mimicking progressive supranuclear palsy (PSP). Before the
      development of typical CJD symptoms, functional imaging supported a diagnosis of
      PSP when [(123)I]-FP-CIT-SPECT showed a defect in striatal dopamine transporter
      binding, while [(18)F]-fluorodeoxyglucose PET showed cortical hypometabolism
      suggestive of Lewy body dementia. However, the postmortem neuropathological
      examination was indicative of CJD only, without tau protein or Lewy body
      findings. This case demonstrates that CJD should be taken into account in rapidly
      progressing atypical cases of parkinsonism, even when functional imaging supports
      a diagnosis of a movement disorder. 

PMID- 24575029
TI  - Magnetic resonance imaging in breath-hold divers with cerebral decompression
      sickness.
AB  - The mechanism of cerebral decompression sickness (DCS) is still unclear. We
      report 2 cases of breath-hold divers with cerebral DCS in whom magnetic resonance
      imaging (MRI) demonstrated distinctive characteristics. One case presented right
      hemiparesthesia, diplopia, and gait disturbance after breath-hold diving into the
      sea at a depth of 20 m. Brain MRI with fluid-attenuated inversion recovery
      (FLAIR) sequence revealed multiple hyperintense lesions in the right frontal
      lobe, bilateral thalamus, pons, and right cerebellar hemisphere. The second case
      presented visual and gait disturbance after repetitive breath-hold diving into
      the sea. FLAIR imaging showed hyperintense areas in the bilateral occipito
      parietal lobes. In both cases, diffusion-weighted imaging and apparent diffusion
      coefficient mapping revealed hyperintense areas in the lesions identified by
      FLAIR. Moreover, follow-up MRI showed attenuation of the FLAIR signal
      abnormalities. These findings are suggestive of transient hyperpermeability in
      the microvasculature as a possible cause of cerebral DCS. 

PMID- 24575031
TI  - Solitary idiopathic choroiditis.
AB  - BACKGROUND: There are multiple conditions associated with the formation of a
      solitary choroidal granuloma. However, in many cases, solitary choroiditis
      remains idiopathic in spite of an extensive systemic evaluation. METHODS: A 26
      year-old man presented with an asymptomatic pale choroidal lesion that had the
      features of solitary idiopathic choroiditis. RESULTS: Optical coherence
      tomography and fundus autofluorescence were performed and showed lesion features.
      CONCLUSIONS: Solitary idiopathic choroiditis is a rare condition of unknown
      aetiology that sometimes can be mistaken as an intraocular tumour. The use of
      emerging multimodal imaging is of great importance in the diagnosis of this
      condition.

PMID- 24575032
TI  - Spontaneous healing of corneal perforation after temporary discontinuation of
      erlotinib treatment.
AB  - PURPOSE: To report a case of corneal perforation associated with oral
      administration of erlotinib and its spontaneous healing after temporary
      discontinuation of drug treatment. CASE REPORT: A 65-year-old man with metastatic
      lung cancer was treated with erlotinib (150 mg/day), a specific tyrosine kinase
      inhibitor of the epidermal growth factor receptor. He was referred to our corneal
      service for the treatment of bilateral corneal disorders, diagnosed with mild
      aqueous-deficient dry eye, and treated by insertion of punctal plugs. His corneal
      epithelial disorders initially improved, but subsequently worsened, as manifested
      by the development of bilateral corneal ulceration with corneal perforation in
      the right eye. The oral administration of erlotinib was interrupted in
      preparation for tectonic keratoplasty, but 2 days later the corneal perforation
      of the right eye and the bilateral epithelial defects had healed spontaneously.
      Treatment with erlotinib was resumed at half the initial dose, and the cornea of
      both eyes has remained apparently healthy. DISCUSSION: Erlotinib may be secreted
      into tear fluid and thereby adversely affect the corneal epithelium. The
      development of corneal epithelial disorders in patients receiving this drug may
      be reversed by reducing its dose.

PMID- 24575033
TI  - Acute macular neuroretinopathy in a 15-year-old boy: optical coherence tomography
      and visual acuity findings.
AB  - PURPOSE: To report a case of acute macular neuroretinopathy (AMN) in a 15-year
      old boy. METHODS: Images were obtained with fundus photography and optical
      coherence tomography (OCT). RESULTS: The patient complained of blurred vision and
      a small central scotoma in the left eye. Left visual acuity was 0.3. Fundus
      photographs revealed a small dark area in the fovea of the left eye. OCT showed
      attenuation of the photoreceptor inner segment (IS)/outer segment (OS) line and
      the OS/retinal pigment epithelium (RPE) line in the left eye. One week after the
      initial visit, left visual acuity had improved to 0.6, and there was partial
      recovery of the IS/OS line with focal thinning of the OS/RPE line. One month
      later, left visual acuity had improved to 0.8, and OCT showed complete
      restoration of the IS/OS line and the OS/RPE line. CONCLUSIONS: To our knowledge,
      this is the youngest patient reported with a diagnosis of AMN. Changes in
      microstructural findings and visual acuity were analogous during recovery of AMN
      in our patient.

PMID- 24575034
TI  - Diagnostic evaluation of ocular toxocariasis using high-penetration optical
      coherence tomography.
AB  - PURPOSE: To study a case with intraretinal Toxocara larvae in a granuloma using
      high-penetration optical coherence tomography (HP-OCT). METHODS: A 50-year-old
      man, who was referred to our clinic with ocular toxocariasis, initially presented
      with granuloma formation in the retina. We followed the treatment-associated
      changes in the toxocariasis lesion by a series of examinations using HP-OCT
      before and after a systemic corticosteroid and anthelmintic therapy. RESULTS: The
      posterior pole granuloma initially appeared as a yellowish-white intraretinal
      lesion with an exudative focus and dye leakage seen on angiography. After
      therapy, the lesion was no longer exudative. During treatment-free periods, an
      intraretinal lesion was seen protruding from the retinal surface into the
      vitreous cavity. HP-OCT confirmed the elevated lesion protruding from the retinal
      surface into the vitreous cavity. With treatment, the protruding focus flattened
      during the following 8 months, but the lesion recurred after the treatment
      stopped. CONCLUSIONS: The findings and clinical course strongly suggested ocular
      toxocariasis. The protruding retinal lesion may have been an ocular manifestation
      of toxocariasis. HP-OCT was useful in the follow-up and diagnosis.

PMID- 24575036
TI  - A case of choroidal neovascularization secondary to unilateral retinal pigment
      epithelium dysgenesis.
AB  - AIM: To report a case of choroidal neovascularization secondary to unilateral
      retinal pigment epithelium dysgenesis (URPED), which was resistant to posterior
      subtenon injection of triamcinolone acetonide (STTA) and intravitreal bevacizumab
      injection (IVB). CASE REPORT: An 8-year-old boy was referred to us because of a
      unilateral unique clinical appearance on funduscopic examination in his left eye
      (OS). A geometric lesion at the retinal pigment epithelium level of the
      interpapillomacular area was disclosed OS. The optic nerve was slightly hyperemic
      OS. Findings from the right fundus examination were normal. Based on these
      characteristic findings, he was diagnosed as having URPED. Best corrected Landolt
      ring chart visual acuity (BCVA) was 1.0 in both eyes. Twenty-three months after
      the first visit, the patient presented with visual disturbance OS. Funduscopic
      examination showed an expansion of the geometric lesion and the development of a
      subfoveal choroidal neovascularization (CNV). BCVA was 0.4 OS. Two-time STTA (40
      mg/1 ml) was performed at the onset of CNV and 6 months later, and additional IVB
      (1.25 mg/0.05 ml) was done 10 months later for the treatment of CNV, but the
      geometric lesion and CNV were resistant to the treatment and continued to expand.
      Seven years after the first visit, the geometric lesion and the CNV kept
      expanding steadily. CONCLUSION: URPED is a rare clinical entity, and the
      prognosis of this disease is still unclear. The visual prognosis may depend on
      whether CNV fully develops.

PMID- 24575035
TI  - Combined intracorneal and subconjunctival bevacizumab injections for recurrent
      visual loss and intraocular hemorrhage from vascularized fibrous downgrowth.
AB  - BACKGROUND: Epithelial and fibrous downgrowths result from persistently leaky
      wounds with conjunctival or corneal epithelium and fibroblasts growing over
      corneal endothelium, iris and angle structures, leading to corneal edema and
      difficult-to-control glaucoma. Therapies have included en bloc resection,
      cryotherapy, endolaser or external photocoagulation and either 5-fluorouracil or
      mitomycin C injections. A new complication and a novel therapy are presented.
      CASE PRESENTATION: A 44-year-old uniocular housewife sustained a large
      corneoscleral laceration following a fall. She underwent primary suturing and was
      subsequently referred for repair of retinal detachment. She underwent resuturing
      of her gaping wound, pars plana vitrectomy and scleral buckle. Postoperative
      visual acuity was 6/120 due to a large macular hole. Visual acuity dropped to
      hand motion 5 times in a recurrent fashion due to diffuse intraocular hemorrhage.
      Vascularized fibrous downgrowth was the identifiable source of bleeding into the
      anterior and posterior chambers. This was controlled by 21 intracorneal and
      subconjunctival bevacizumab injections over 2.5 years of therapy. CONCLUSION:
      Repeated bevacizumab injections can control intraocular bleeding from new vessels
      accompanying fibrous downgrowth with preservation of vision.

PMID- 24575037
TI  - Enhanced synaptic transmission at the squid giant synapse by artificial seawater
      based on physically modified saline.
AB  - Superfusion of the squid giant synapse with artificial seawater (ASW) based on
      isotonic saline containing oxygen nanobubbles (RNS60 ASW) generates an
      enhancement of synaptic transmission. This was determined by examining the
      postsynaptic response to single and repetitive presynaptic spike activation,
      spontaneous transmitter release, and presynaptic voltage clamp studies. In the
      presence of RNS60 ASW single presynaptic stimulation elicited larger postsynaptic
      potentials (PSP) and more robust recovery from high frequency stimulation than in
      control ASW. Analysis of postsynaptic noise revealed an increase in spontaneous
      transmitter release with modified noise kinetics in RNS60 ASW. Presynaptic
      voltage clamp demonstrated an increased EPSP, without an increase in presynaptic
      ICa(++) amplitude during RNS60 ASW superfusion. Synaptic release enhancement
      reached stable maxima within 5-10 min of RNS60 ASW superfusion and was maintained
      for the entire recording time, up to 1 h. Electronmicroscopic morphometry
      indicated a decrease in synaptic vesicle density and the number at active zones
      with an increase in the number of clathrin-coated vesicles (CCV) and large
      endosome-like vesicles near junctional sites. Block of mitochondrial ATP
      synthesis by presynaptic injection of oligomycin reduced spontaneous release and
      prevented the synaptic noise increase seen in RNS60 ASW. After ATP block the
      number of vesicles at the active zone and CCV was reduced, with an increase in
      large vesicles. The possibility that RNS60 ASW acts by increasing mitochondrial
      ATP synthesis was tested by direct determination of ATP levels in both
      presynaptic and postsynaptic structures. This was implemented using
      luciferin/luciferase photon emission, which demonstrated a marked increase in ATP
      synthesis following RNS60 administration. It is concluded that RNS60 positively
      modulates synaptic transmission by up-regulating ATP synthesis, thus leading to
      synaptic transmission enhancement. 

PMID- 24575038
TI  - Chronic cerebral hypoperfusion causes decrease of O-GlcNAcylation,
      hyperphosphorylation of tau and behavioral deficits in mice.
AB  - Chronic cerebral hypoperfusion (CCH) is one of the causes of vascular dementia
      (VaD) and is also an etiological factor for Alzheimer's disease (AD). However,
      how CCH causes cognitive impairment and contributes to Alzheimer's pathology is
      poorly understood. Here we produced a mouse model of CCH by unilateral common
      carotid artery occlusion (UCCAO) and studied the behavioral changes and brain
      abnormalities in mice 2.5 months after UCCAO. We found that CCH caused
      significant short-term memory deficits and mild long-term spatial memory
      impairment, as well as decreased level of protein O-GlcNAcylation, increased
      level of tau phosphorylation, dysregulated synaptic proteins and insulin
      signaling, and selective neurodegeneration in the brain. These findings provide
      mechanistic insight into the effects of CCH on memory and cognition and the
      likely link between AD and VaD. 

PMID- 24575040
TI  - Increased metal content in the TDP-43(A315T) transgenic mouse model of
      frontotemporal lobar degeneration and amyotrophic lateral sclerosis.
AB  - Disrupted metal homeostasis is a consistent feature of neurodegenerative disease
      in humans and is recapitulated in mouse models of Alzheimer's disease,
      Parkinson's disease, amyotrophic lateral sclerosis (ALS) and neuronal ceriod
      lipofuscinosis. While the definitive pathogenesis of neurodegenerative disease in
      humans remains to be fully elucidated, disease-like symptoms in the mouse models
      are all driven by the presence or over-expression of a putative pathogenic
      protein, indicating an in vivo relationship between expression of these proteins,
      disrupted metal homeostasis and the symptoms of neuronal failure. Recently it was
      established that mutant TAR DNA binding protein-43 (TDP-43) is associated with
      the development of frontotemporal lobar degeneration and ALS. Subsequent
      development of transgenic mice that express human TDP-43 carrying the disease
      causing A315T mutation has provided new opportunity to study the underlying
      mechanisms of TDP-43-related neurodegenerative disease. We assessed the cognitive
      and locomotive phenotype of TDP-43 (A315T) mice and their wild-type littermates
      and also assessed bulk metal content of brain and spinal cord tissues. Metal
      levels in the brain were not affected by the expression of mutant TDP-43, but
      zinc, copper, and manganese levels were all increased in the spinal cords of TDP
      43 (A315T) mice when compared to wild-type littermates. Performance of the TDP-43
      (A315T) mice in the Y-maze test for cognitive function was not significantly
      different to wild-type mice. By contrast, performance of the TDP-43 (A315T) in
      the rotarod test for locomotive function was consistently worse than wild-type
      mice. These preliminary in vivo data are the first to show that expression of a
      disease-causing form of TDP-43 is sufficient to disrupt metal ion homeostasis in
      the central nervous system. Disrupted metal ion homeostasis in the spinal cord
      but not the brain may explain why the TDP-43 (A315T) mice show symptoms of
      locomotive decline and not cognitive decline. 

PMID- 24575039
TI  - Aged rats are hypo-responsive to acute restraint: implications for psychosocial
      stress in aging.
AB  - Cognitive processes associated with prefrontal cortex and hippocampus decline
      with age and are vulnerable to disruption by stress. The stress/stress
      hormone/allostatic load hypotheses of brain aging posit that brain aging, at
      least in part, is the manifestation of life-long stress exposure. In addition, as
      humans age, there is a profound increase in the incidence of new onset stressors,
      many of which are psychosocial (e.g., loss of job, death of spouse, social
      isolation), and aged humans are well-understood to be more vulnerable to the
      negative consequences of such new-onset chronic psychosocial stress events.
      However, the mechanistic underpinnings of this age-related shift in chronic
      psychosocial stress response, or the initial acute phase of that chronic
      response, have been less well-studied. Here, we separated young (3 month) and
      aged (21 month) male F344 rats into control and acute restraint (an animal model
      of psychosocial stress) groups (n = 9-12/group). We then assessed hippocampus
      associated behavioral, electrophysiological, and transcriptional outcomes, as
      well as blood glucocorticoid and sleep architecture changes. Aged rats showed
      characteristic water maze, deep sleep, transcriptome, and synaptic sensitivity
      changes compared to young. Young and aged rats showed similar levels of distress
      during the 3 h restraint, as well as highly significant increases in blood
      glucocorticoid levels 21 h after restraint. However, young, but not aged, animals
      responded to stress exposure with water maze deficits, loss of deep sleep and
      hyperthermia. These results demonstrate that aged subjects are hypo-responsive to
      new-onset acute psychosocial stress, which may have negative consequences for
      long-term stress adaptation and suggest that age itself may act as a stressor
      occluding the influence of new onset stressors. 

PMID- 24575042
TI  - CaMKIIdelta subtypes: localization and function.
AB  - In this review we discuss the localization and function of the known subtypes of
      calcium/calmodulin dependent protein kinase IIdelta (CaMKIIdelta) and their role
      in cardiac physiology and pathophysiology. The CaMKII holoenzyme is comprised of
      multiple subunits that are encoded by four different genes called CaMKIIalpha,
      beta, gamma, and delta. While these four genes have a high degree of sequence
      homology, they are expressed in different tissues. CaMKIIalpha and beta are
      expressed in neuronal tissue while gamma and delta are present throughout the
      body, including in the heart. Both CaMKIIgamma and delta are alternatively
      spliced in the heart to generate multiple subtypes. CaMKIIdelta is the
      predominant cardiac isoform and is alternatively spliced in the heart to generate
      the CaMKIIdeltaB subtype or the slightly less abundant deltaC subtype. The
      CaMKIIdeltaB mRNA sequence contains a 33bp insert not present in deltaC that
      codes for an 11-amino acid nuclear localization sequence. This review focuses on
      the localization and function of the CaMKIIdelta subtypes deltaB and deltaC and
      the role of these subtypes in arrhythmias, contractile dysfunction, gene
      transcription, and the regulation of Ca(2+) handling. 

PMID- 24575041
TI  - Complex GABAB receptor complexes: how to generate multiple functionally distinct
      units from a single receptor.
AB  - The main inhibitory neurotransmitter, GABA, acts on both ligand-gated and G
      protein-coupled receptors, the GABAA/C and GABAB receptors, respectively. The
      later play important roles in modulating many synapses, both at the pre- and post
      synaptic levels, and are then still considered as interesting targets to treat a
      number of brain diseases, including addiction. For many years, several subtypes
      of GABAB receptors were expected, but cloning revealed only two genes that work
      in concert to generate a single type of GABAB receptor composed of two subunits.
      Here we will show that the signaling complexity of this unit receptor type can be
      largely increased through various ways, including receptor stoichiometry, subunit
      isoforms, cell-surface expression and localization, crosstalk with other
      receptors, or interacting proteins. These recent data revealed how complexity of
      a receptor unit can be increased, observation that certainly are not unique to
      the GABAB receptor. 

PMID- 24575043
TI  - Hypocretin (orexin) regulation of sleep-to-wake transitions.
AB  - The hypocretin (Hcrt), also known as orexin, peptides are essential for arousal
      stability. Here we discuss background information about the interaction of Hcrt
      with other neuromodulators, including norepinephrine and acetylcholine probed
      with optogenetics. We conclude that Hcrt neurons integrate metabolic, circadian
      and limbic inputs and convey this information to a network of neuromodulators,
      each of which has a different role on the dynamic of sleep-to-wake transitions.
      This model may prove useful to predict the effects of orexin receptor antagonists
      in sleep disorders and other conditions. 

PMID- 24575047
TI  - FGF2 activates TRPC and Ca(2+) signaling leading to satellite cell activation.
AB  - Satellite cells, as stem cells of adult skeletal muscle, are tightly associated
      with the differentiated muscle fibers and remain quiescent in the absence of
      muscle damage. In response to an injury, the quiescent satellite cell is
      activated by soluble factors, including FGFs released from injured myofibers.
      Using immunostaining, we here first show that TRPC1 channels are highly expressed
      in satellite cells attached to muscle fibers. Since CD34, a traditional stem cell
      marker, was recently found to be expressed in skeletal muscle satellite cells we
      labeled living satellite cells in their physiological niche associated with host
      FDB fibers using anti-CD34-FITC antibody. We then monitored intra-cellular
      calcium in anti-CD34-FITC labeled satellite cells attached to muscle fibers using
      the calcium sensitive dye X rhod-1 which has little fluorescence cross talk with
      FITC. FGF2 increased intracellular calcium in satellite cells, which was
      antagonized by the TRPC channel blocker SKF 96365. Immunostaining showed that
      NFATc3 is highly expressed in satellite cells, but not in host FDB fibers.
      Elevation of intracellular calcium by FGF2 is accompanied by nuclear
      translocation of NFATc3 and NFATc2 and by an increase in the number of MyoD
      positive cells per muscle fiber, both of which were attenuated by TRPC blocker
      SKF 96365. Our results suggest a novel pathway of satellite cell activation where
      FGF2 enhances calcium influx through a TRPC channel, and the increased cytosolic
      calcium leads to both NFATc3 and NFATc2 nuclear translocation and enhanced number
      of MyoD positive satellite cells per muscle fiber. 

PMID- 24575045
TI  - Molecular pathways of pannexin1-mediated neurotoxicity.
AB  - Pannexin1 (Panx1) forms non-selective membrane channels, structurally similar to
      gap junction hemichannels, and are permeable to ions, nucleotides, and other
      small molecules below 900 Da. Panx1 activity has been implicated in paracrine
      signaling and inflammasome regulation. Recent studies in different animal models
      showed that overactivation of Panx1 correlates with a selective demise of several
      types of neurons, including retinal ganglion cells, brain pyramidal, and enteric
      neurons. The list of Panx1 activators includes extracellular ATP, glutamate, high
      K(+), Zn(2+), fibroblast growth factors (FGFs),pro-inflammatory cytokines, and
      elevation of intracellular Ca(2+). Most of these molecules are released following
      mechanical, ischemic, or inflammatory injury of the CNS, and rapidly activate the
      Panx1 channel. Prolonged opening of Panx1 channel induced by these "danger
      signals" triggers a cascade of neurotoxic events capable of killing cells. The
      most vulnerable cell type are neurons that express high levels of Panx1.
      Experimental evidence suggests that Panx1 channels mediate at least two distinct
      neurotoxic processes: increased permeability of the plasma membrane and
      activation of the inflammasome in neurons and glia. Importantly, both
      pharmacological and genetic inactivation of Panx1 suppresses both these
      processes, providing a marked protection in several disease and injury models.
      These findings indicate that external danger signals generated after diverse
      types of injuries converge to activate Panx1. In this review we discuss molecular
      mechanisms associated with Panx1 toxicity and the crosstalk between different
      pathways. 

PMID- 24575044
TI  - Connexin hemichannels in the lens.
AB  - The normal function and survival of cells in the avascular lens is facilitated by
      intercellular communication through an extensive network of gap junctions formed
      predominantly by three connexins (Cx43, Cx46, and Cx50). In expression systems,
      these connexins can all induce hemichannel currents, but other lens proteins
      (e.g., pannexin1) can also induce similar currents. Hemichannel currents have
      been detected in isolated lens fiber cells. These hemichannels may make
      significant contributions to normal lens physiology and pathophysiology. Studies
      of some connexin mutants linked to congenital cataracts have implicated
      hemichannels with aberrant voltage-dependent gating or modulation by divalent
      cations in disease pathogenesis. Hemichannels may also contribute to age- and
      disease-related cataracts. 

PMID- 24575046
TI  - Relevance of gap junctions and large pore channels in traumatic brain injury.
AB  - In case of traumatic brain injury (TBI), occurrence of central nervous tissue
      damage is frequently aligned with local modulations of neuronal and glial gap
      junction channel expression levels. The degree of gap junctional protein
      expression and intercellular coupling efficiency, as well as hemichannel function
      has substantially impact on the course of trauma recovery and outcome. During
      TBI, gap junctions are especially involved in the intercellular molecule
      trafficking on repair of blood vessels and the regulation of vasomotor tone.
      Furthermore, gliosis and astrocytic swelling due to mechanical strain injury
      point out the consequences of derailed gap junction communication. This review
      addresses the outstanding role of gap junction channels in TBI pathophysiology
      and links the current state of results to applied clinical procedures as well as
      perspectives in acute and long-term treatment options. 

PMID- 24575048
TI  - Gap junctions in C. elegans.
AB  - As in other multicellular organisms, the nematode Caenorhabditis elegans uses gap
      junctions to provide direct cell-to-cell contact. The nematode gap junctions are
      formed by innexins (invertebrate analogs of the connexins); a family of proteins
      that surprisingly share no primary sequence homology, but do share structural and
      functional similarity with connexins. The model organism C. elegans contains 25
      innexin genes and innexins are found in virtually all cell types and tissues.
      Additionally, many innexins have dynamic expression patterns during development,
      and several innexins are essential genes in the nematode. C. elegans is a popular
      invertebrate model due to several features including a simple anatomy, a complete
      cell lineage, sequenced genome and an array of genetic resources. Thus, the worm
      has potential to offer valuable insights into the various functions of gap
      junction mediated intercellular communication. 

PMID- 24575049
TI  - Role of the bicarbonate-responsive soluble adenylyl cyclase in pH sensing and
      metabolic regulation.
AB  - The evolutionarily conserved soluble adenylyl cyclase (sAC, adcy10) was recently
      identified as a unique source of cAMP in the cytoplasm and the nucleus. Its
      activity is regulated by bicarbonate and fine-tuned by calcium. As such, and in
      conjunction with carbonic anhydrase (CA), sAC constitutes an HCO(-) 3/CO(-) 2/pH
      sensor. In both alpha-intercalated cells of the collecting duct and the clear
      cells of the epididymis, sAC is expressed at significant level and involved in pH
      homeostasis via apical recruitment of vacuolar H(+)-ATPase (VHA) in a PKA
      dependent manner. In addition to maintenance of pH homeostasis, sAC is also
      involved in metabolic regulation such as coupling of Krebs cycle to oxidative
      phosphorylation via bicarbonate/CO2 sensing. Additionally, sAC also regulates
      CFTR channel and plays an important role in regulation of barrier function and
      apoptosis. These observations suggest that sAC, via bicarbonate-sensing, plays an
      important role in maintaining homeostatic status of cells against fluctuations in
      their microenvironment. 

PMID- 24575051
TI  - Glycopyrrolate does not influence the visual or motor-induced increase in
      regional cerebral perfusion.
AB  - Acetylcholine may contribute to the increase in regional cerebral blood flow
      (rCBF) during cerebral activation since glycopyrrolate, a potent inhibitor of
      acetylcholine, abolishes the exercise-induced increase in middle cerebral artery
      mean flow velocity. We tested the hypothesis that cholinergic vasodilatation is
      important for the increase in rCBF during cerebral activation. The subjects were
      11 young healthy males at an age of 24 +/- 3 years (mean +/- SD). We used
      arterial spin labeling and blood oxygen level dependent (BOLD) functional
      magnetic resonance imaging (fMRI) to evaluate rCBF with and without intravenous
      glycopyrrolate during a handgrip motor task and visual stimulation.
      Glycopyrrolate increased heart rate from 56 +/- 9 to 114 +/- 14 beats/min (mean
      +/- SD; p < 0.001), mean arterial pressure from 86 +/- 8 to 92 +/- 12 mmHg, and
      cardiac output from 5.6 +/- 1.4 to 8.0 +/- 1.7 l/min. Glycopyrrolate had,
      however, no effect on the arterial spin labeling or BOLD responses to the
      handgrip motor task or to visual stimulation. This study indicates that during a
      handgrip motor task and visual stimulation, the increase in rCBF is unaffected by
      blockade of acetylcholine receptors by glycopyrrolate. Further studies on the
      effect of glycopyrrolate on middle cerebral artery diameter are needed to
      evaluate the influence of glycopyrrolate on mean flow velocity during intense
      exercise. 

PMID- 24575050
TI  - An emerging need for developing new models for myocardial infarction as a chronic
      complex disease: lessons learnt from animal vs. human studies on cardioprotective
      effects of Erythropoietin in reperfused myocardium.

PMID- 24575053
TI  - Enoxacin Elevates MicroRNA Levels in Rat Frontal Cortex and Prevents Learned
      Helplessness.
AB  - Major depressive disorder (MDD) is a major public health concern. Despite
      tremendous advancement, the pathogenic mechanisms associated with MDD are still
      unclear. Moreover, a significant number of MDD subjects do not respond to the
      currently available medication. MicroRNAs (miRNAs) are a class of small non
      coding RNAs that control gene expression by modulating translation, mRNA
      degradation or stability of mRNA targets. The role of miRNAs in disease
      pathophysiology is emerging rapidly. Recently, we reported that miRNA expression
      is down-regulated in frontal cortex of depressed suicide subjects, and that rats
      exposed to repeated inescapable shock show differential miRNA changes depending
      on whether they exhibited normal adaptive responses or learned helpless (LH)
      behavior. Enoxacin, a fluoroquinolone used clinically as an anti-bacterial
      compound, enhances the production of miRNAs in vitro and in peripheral tissues in
      vivo, but has not yet been tested as an experimental tool to study the relation
      of miRNA expression to neural functions or behavior. Treatment of rats with 10 or
      25 mg/kg enoxacin for 1 week increased the expression of miRNAs in frontal cortex
      and decreased the proportion of rats exhibiting LH behavior following inescapable
      shock. Further studies are warranted to learn whether enoxacin may ameliorate
      depressive behavior in other rodent paradigms and in human clinical situations,
      and if so whether its mechanism is due to upregulation of miRNAs. 

PMID- 24575054
TI  - Anisotropic kernels for coordinate-based meta-analyses of neuroimaging studies.
AB  - Peak-based meta-analyses of neuroimaging studies create, for each study, a brain
      map of effect size or peak likelihood by convolving a kernel with each reported
      peak. A kernel is a small matrix applied in order that voxels surrounding the
      peak have a value similar to, but slightly lower than that of the peak. Current
      kernels are isotropic, i.e., the value of a voxel close to a peak only depends on
      the Euclidean distance between the voxel and the peak. However, such perfect
      spheres of effect size or likelihood around the peak are rather implausible: a
      voxel that correlates with the peak across individuals is more likely to be part
      of the cluster of significant activation or difference than voxels uncorrelated
      with the peak. This paper introduces anisotropic kernels, which assign different
      values to the different neighboring voxels based on the spatial correlation
      between them. They are specifically developed for effect-size signed differential
      mapping (ES-SDM), though might be easily implemented in other meta-analysis
      packages such as activation likelihood estimation (ALE). The paper also describes
      the creation of the required correlation templates for gray matter/BOLD response,
      white matter, cerebrospinal fluid, and fractional anisotropy. Finally, the new
      method is validated by quantifying the accuracy of the recreation of effect size
      maps from peak information. This empirical validation showed that the optimal
      degree of anisotropy and full-width at half-maximum (FWHM) might vary largely
      depending on the specific data meta-analyzed. However, it also showed that the
      recreation substantially improved and did not depend on the FWHM when full
      anisotropy was used. Based on these results, we recommend the use of fully
      anisotropic kernels in ES-SDM and ALE, unless optimal meta-analysis-specific
      parameters can be estimated based on the recreation of available statistical
      maps. The new method and templates are freely available at
      http://www.sdmproject.com/. 

PMID- 24575055
TI  - Inpatient cognitive behavior therapy for adolescents with anorexia nervosa:
      immediate and longer-term effects.
AB  - INTRODUCTION: Inpatient treatment for anorexia nervosa is often successful in
      restoring body weight, but a high percentage of patients relapse following
      discharge. The aim of the present study was to establish the immediate and longer
      term effects of a novel inpatient program for adolescents that was designed to
      produce enduring change. METHOD: Twenty-seven consecutive patients with severe
      anorexia nervosa were admitted to a 20-week inpatient treatment program based on
      the enhanced cognitive behavior therapy (CBT-E). The patients were assessed
      before and after hospitalization, and 6 and 12 months later. RESULTS: Twenty-six
      patients (96%) completed the program. In these patients, there was a substantial
      improvement in weight, eating disorder features, and general psychopathology that
      was well maintained at 12-month follow-up. CONCLUSION: These findings suggest
      that inpatient CBT-E is a promising approach to the treatment of adolescents with
      severe anorexia nervosa.

PMID- 24575052
TI  - Advancements in stem cells treatment of skeletal muscle wasting.
AB  - Muscular dystrophies (MDs) are a heterogeneous group of inherited disorders, in
      which progressive muscle wasting and weakness is often associated with exhaustion
      of muscle regeneration potential. Although physiological properties of skeletal
      muscle tissue are now well known, no treatments are effective for these diseases.
      Muscle regeneration was attempted by means transplantation of myogenic cells
      (from myoblast to embryonic stem cells) and also by interfering with the
      malignant processes that originate in pathological tissues, such as uncontrolled
      fibrosis and inflammation. Taking into account the advances in the isolation of
      new subpopulation of stem cells and in the creation of artificial stem cell
      niches, we discuss how these emerging technologies offer great promises for
      therapeutic approaches to muscle diseases and muscle wasting associated with
      aging. 

PMID- 24575056
TI  - Oculometric variations during mind wandering.
AB  - A significant body of literature supports the contention that pupil size varies
      depending on cognitive load, affective state, and level of drowsiness. Here we
      assessed whether oculometric measures such as gaze position, blink frequency and
      pupil size were correlated with the occurrence and time course of self-reported
      mind-wandering episodes. We recorded the pupil size of two subjects engaged in a
      monotonous breath counting task while keeping their eyes on a fixation cross.
      This task is conducive to producing mind-wandering episodes. Each subject
      performed ten 20-min sessions, for total duration of about 4 h. Subjects were
      instructed to report spontaneous mind-wandering episodes by pressing a button
      when they lost count of their breath. After each button press, subjects filled in
      a short questionnaire describing the characteristics of their mind-wandering
      episode. We observed larger pupil size during the breath-focusing period compared
      to the mind-wandering period (p < 0.01 for both subjects). Our findings
      contradict previous research showing a higher baseline pupil size during mind
      wandering episodes in visual tasks. We discuss possible explanations for this
      discrepancy. We also analyzed nine other oculometric measures including blink
      rate, blink duration and gaze position. We built a support vector machine (SVM)
      classifier and showed that mean pupil size was the most reliable predictor of
      mind wandering in both subjects. The classification accuracy of mind wandering
      data segments vs. breath-focusing data segments was 81% for the first subject and
      77% for the second subject. Additionally, we analyzed oculometric measures in
      light of the phenomenological data collected in the questionnaires. We showed
      that how well subjects remembered their thoughts while mind wandering was
      positively correlated with pupil size (subject 1, p < 0.001; subject 2, p <
      0.05). Feelings of well being were also positively correlated with pupil size
      (subject 1, p < 0.001; subject 2, p < 0.001). Our results suggest that
      oculometric data could be used as a neurocognitive marker of mind-wandering
      episodes. 

PMID- 24575057
TI  - Advert saliency distracts children's visual attention during task-oriented
      internet use.
AB  - The general research question of the present study was to assess the impact of
      visually salient online adverts on children's task-oriented internet use. In
      order to answer this question, an experimental study was constructed in which 9-
      and 12-year-old Swedish children were asked to solve a number of tasks while
      interacting with a mockup website. In each trial, web adverts in several saliency
      conditions were presented. By both measuring children's task accuracy, as well as
      the visual processing involved in solving these tasks, this study allows us to
      infer how two types of visual saliency affect children's attentional behavior,
      and whether such behavioral effects also impacts their task performance. Analyses
      show that low-level visual features and task relevance in online adverts have
      different effects on performance measures and process measures respectively.
      Whereas task performance is stable with regard to several advert saliency
      conditions, a marked effect is seen on children's gaze behavior. On the other
      hand, task performance is shown to be more sensitive to individual differences
      such as age, gender and level of gaze control. The results provide evidence about
      cognitive and behavioral distraction effects in children's task-oriented internet
      use caused by visual saliency in online adverts. The experiment suggests that
      children to some extent are able to compensate for behavioral effects caused by
      distracting visual stimuli when solving prospective memory tasks. Suggestions are
      given for further research into the interdiciplinary area between media research
      and cognitive science. 

PMID- 24575058
TI  - Lexical orthography acquisition: Is handwriting better than spelling aloud?
AB  - Lexical orthography acquisition is currently described as the building of links
      between the visual forms and the auditory forms of whole words. However, a
      growing body of data suggests that a motor component could further be involved in
      orthographic acquisition. A few studies support the idea that reading plus
      handwriting is a better lexical orthographic learning situation than reading
      alone. However, these studies did not explore which of the cognitive processes
      involved in handwriting enhanced lexical orthographic acquisition. Some findings
      suggest that the specific movements memorized when learning to write may
      participate in the establishment of orthographic representations in memory. The
      aim of the present study was to assess this hypothesis using handwriting and
      spelling aloud as two learning conditions. In two experiments, fifth graders were
      asked to read complex pseudo-words embedded in short sentences. Immediately after
      reading, participants had to recall the pseudo-words' spellings either by
      spelling them aloud or by handwriting them down. One week later, orthographic
      acquisition was tested using two post-tests: a pseudo-word production task
      (spelling by hand in Experiment 1 or spelling aloud in Experiment 2) and a pseudo
      word recognition task. Results showed no significant difference in pseudo-word
      recognition between the two learning conditions. In the pseudo-word production
      task, orthography learning improved when the learning and post-test conditions
      were similar, thus showing a massive encoding-retrieval match effect in the two
      experiments. However, a mixed model analysis of the pseudo-word production
      results revealed a significant learning condition effect which remained after
      control of the encoding-retrieval match effect. This later finding suggests that
      orthography learning is more efficient when mediated by handwriting than by
      spelling aloud, whatever the post-test production task. 

PMID- 24575060
TI  - Gaze-dependent spatial updating of tactile targets in a localization task.
AB  - There is concurrent evidence that visual reach targets are represented with
      respect to gaze. For tactile reach targets, we previously showed that an effector
      movement leads to a shift from a gaze-independent to a gaze-dependent reference
      frame. Here we aimed to unravel the influence of effector movement (gaze shift)
      on the reference frame of tactile stimuli using a spatial localization task
      (yes/no paradigm). We assessed how gaze direction (fixation left/right) alters
      the perceived spatial location (point of subjective equality) of sequentially
      presented tactile standard and visual comparison stimuli while effector movement
      (gaze fixed/shifted) and stimulus order (vis-tac/tac-vis) were varied. In the
      fixed-gaze condition, subjects maintained gaze at the fixation site throughout
      the trial. In the shifted-gaze condition, they foveated the first stimulus, then
      made a saccade toward the fixation site where they held gaze while the second
      stimulus appeared. Only when an effector movement occurred after the encoding of
      the tactile stimulus (shifted-gaze, tac-vis), gaze similarly influenced the
      perceived location of the tactile and the visual stimulus. In contrast, when gaze
      was fixed or a gaze shift occurred before encoding of the tactile stimulus, gaze
      differentially affected the perceived spatial relation of the tactile and the
      visual stimulus suggesting gaze-dependent coding of only one of the two stimuli.
      Consistent with previous findings this implies that visual stimuli vary with gaze
      irrespective of whether gaze is fixed or shifted. However, a gaze-dependent
      representation of tactile stimuli seems to critically depend on an effector
      movement (gaze shift) after tactile encoding triggering spatial updating of
      tactile targets in a gaze-dependent reference frame. Together with our recent
      findings on tactile reaching, the present results imply similar underlying
      reference frames for tactile spatial perception and action. 

PMID- 24575059
TI  - A "Misfit" Theory of Spontaneous Conscious Odor Perception (MITSCOP): reflections
      on the role and function of odor memory in everyday life.
AB  - Our senses have developed as an answer to the world we live in (Gibson, 1966) and
      so have the forms of memory that accompany them. All senses serve different
      purposes and do so in different ways. In vision, where orientation and object
      recognition are important, memory is strongly linked to identification. In
      olfaction, the guardian of vital functions such as breathing and food ingestion,
      perhaps the most important (and least noticed and researched) role of odor memory
      is to help us not to notice the well-known odors or flavors in our everyday
      surroundings, but to react immediately to the unexpected ones. At the same time
      it provides us with a feeling of safety when our expectancies are met. All this
      happens without any smelling intention or conscious knowledge of our
      expectations. Identification by odor naming is not involved in this and people
      are notoriously bad at it. Odors are usually best identified via the episodic
      memory of the situation in which they once occurred. Spontaneous conscious odor
      perception normally only occurs in situations where attention is demanded, either
      because the inhaled air or the food smell is particularly good or particularly
      bad and people search for its source or because people want to actively enjoy the
      healthiness and pleasantness of their surroundings or food. Odor memory is
      concerned with novelty detection rather than with recollection of odors. In this
      paper, these points are illustrated with experimental results and their
      consequences for doing ecologically valid odor memory research are drawn.
      Furthermore, suggestions for ecologically valid research on everyday odor memory
      and some illustrative examples are given. 

PMID- 24575061
TI  - Improved control of exogenous attention in action video game players.
AB  - Action video game players (VGPs) have demonstrated a number of attentional
      advantages over non-players. Here, we propose that many of those benefits might
      be underpinned by improved control over exogenous (i.e., stimulus-driven)
      attention. To test this we used an anti-cueing task, in which a sudden-onset cue
      indicated that the target would likely appear in a separate location on the
      opposite side of the fixation point. When the time between the cue onset and the
      target onset was short (40 ms), non-players (nVGPs) showed a typical exogenous
      attention effect. Their response times were faster to targets presented at the
      cued (but less probable) location compared with the opposite (more probable)
      location. VGPs, however, were less likely to have their attention drawn to the
      location of the cue. When the onset asynchrony was long (600 ms), VGPs and nVGPs
      were equally able to endogenously shift their attention to the likely (opposite)
      target location. In order to rule out processing-speed differences as an
      explanation for this result, we also tested VGPs and nVGPs on an attentional
      blink (AB) task. In a version of the AB task that minimized demands on task
      switching and iconic memory, VGPs and nVGPs did not differ in second target
      identification performance (i.e., VGPs had the same magnitude of AB as nVGPs),
      suggesting that the anti-cueing results were due to flexible control over
      exogenous attention rather than to more general speed-of-processing differences. 

PMID- 24575063
TI  - Discrepancies between implicit and explicit self-concepts of intelligence:
      relations to modesty, narcissism, and achievement motivation.
AB  - Previous research has shown that different configurations of the implicit self
      concept of intelligence (iSCI) and the explicit self-concept of intelligence
      (eSCI) are consistently related to individuals' performance on different
      intelligence tests (Dislich etal., 2012). The results indicated that any
      discrepant configuration between the iSCI and the eSCI impairs performance. In
      the present study, how correspondence between the iSCI and the eSCI is related to
      intelligence test performance as well as personality traits of modesty (low eSCI,
      high iSCI), narcissism (high eSCI, low iSCI), and achievement motivation was
      investigated. Furthermore, a moderated mediation analysis showed that the
      relation between the iSCI-eSCI configurations and intelligence test performance
      was mediated by achievement motivation for modest individuals. 

PMID- 24575062
TI  - Phonological iconicity.
AB  - The arbitrariness of the linguistic sign is a fundamental assumption in modern
      linguistic theory. In recent years, however, a growing amount of research has
      investigated the nature of non-arbitrary relations between linguistic sounds and
      semantics. This review aims at illustrating the amount of findings obtained so
      far and to organize and evaluate different lines of research dedicated to the
      issue of phonological iconicity. In particular, we summarize findings on the
      processing of onomatopoetic expressions, ideophones, and phonaesthemes, relations
      between syntactic classes and phonology, as well as sound-shape and sound-affect
      correspondences at the level of phonemic contrasts. Many of these findings have
      been obtained across a range of different languages suggesting an internal
      relation between sublexical units and attributes as a potentially universal
      pattern. 

PMID- 24575064
TI  - Walking across Wikipedia: a scale-free network model of semantic memory
      retrieval.
AB  - Semantic knowledge has been investigated using both online and offline methods.
      One common online method is category recall, in which members of a semantic
      category like "animals" are retrieved in a given period of time. The order,
      timing, and number of retrievals are used as assays of semantic memory processes.
      One common offline method is corpus analysis, in which the structure of semantic
      knowledge is extracted from texts using co-occurrence or encyclopedic methods.
      Online measures of semantic processing, as well as offline measures of semantic
      structure, have yielded data resembling inverse power law distributions. The aim
      of the present study is to investigate whether these patterns in data might be
      related. A semantic network model of animal knowledge is formulated on the basis
      of Wikipedia pages and their overlap in word probability distributions. The
      network is scale-free, in that node degree is related to node frequency as an
      inverse power law. A random walk over this network is shown to simulate a number
      of results from a category recall experiment, including power law-like
      distributions of inter-response intervals. Results are discussed in terms of
      theories of semantic structure and processing. 

PMID- 24575065
TI  - Global scene layout modulates contextual learning in change detection.
AB  - Change in the visual scene often goes unnoticed - a phenomenon referred to as
      "change blindness." This study examined whether the hierarchical structure, i.e.,
      the global-local layout of a scene can influence performance in a one-shot change
      detection paradigm. To this end, natural scenes of a laid breakfast table were
      presented, and observers were asked to locate the onset of a new local object.
      Importantly, the global structure of the scene was manipulated by varying the
      relations among objects in the scene layouts. The very same items were either
      presented as global-congruent (typical) layouts or as global-incongruent (random)
      arrangements. Change blindness was less severe for congruent than for incongruent
      displays, and this congruency benefit increased with the duration of the
      experiment. These findings show that global layouts are learned, supporting
      detection of local changes with enhanced efficiency. However, performance was not
      affected by scene congruency in a subsequent control experiment that required
      observers to localize a static discontinuity (i.e., an object that was missing
      from the repeated layouts). Our results thus show that learning of the global
      layout is particularly linked to the local objects. Taken together, our results
      reveal an effect of "global precedence" in natural scenes. We suggest that
      relational properties within the hierarchy of a natural scene are governed, in
      particular, by global image analysis, reducing change blindness for local objects
      through scene learning. 

PMID- 24575066
TI  - Music reduces pain and increases functional mobility in fibromyalgia.
AB  - The pain in Fibromyalgia (FM) is difficult to treat and functional mobility seems
      to be an important comorbidity in these patients that could evolve into a
      disability. In this study we wanted to investigate the analgesic effects of music
      in FM pain. Twenty-two FM patients were passively exposed to (1) self-chosen,
      relaxing, pleasant music, and to (2) a control auditory condition (pink noise).
      They rated pain and performed the "timed-up & go task (TUG)" to measure
      functional mobility after each auditory condition. Listening to relaxing,
      pleasant, self-chosen music reduced pain and increased functional mobility
      significantly in our FM patients. The music-induced analgesia was significantly
      correlated with the TUG scores; thereby suggesting that the reduction in pain
      unpleasantness increased functional mobility. Notably, this mobility improvement
      was obtained with music played prior to the motor task (not during), therefore
      the effect cannot be explained merely by motor entrainment to a fast rhythm.
      Cognitive and emotional mechanisms seem to be central to music-induced analgesia.
      Our findings encourage the use of music as a treatment adjuvant to reduce chronic
      pain in FM and increase functional mobility thereby reducing the risk of
      disability. 

PMID- 24575067
TI  - Emergent structured transition from variation to repetition in a biologically
      plausible model of learning in basal ganglia.
AB  - Often, when animals encounter an unexpected sensory event, they transition from
      executing a variety of movements to repeating the movement(s) that may have
      caused the event. According to a recent theory of action discovery (Redgrave and
      Gurney, 2006), repetition allows the animal to represent those movements, and the
      outcome, as an action for later recruitment. The transition from variation to
      repetition often follows a non-random, structured, pattern. While the structure
      of the pattern can be explained by sophisticated cognitive mechanisms, simpler
      mechanisms based on dopaminergic modulation of basal ganglia (BG) activity are
      thought to underlie action discovery (Redgrave and Gurney, 2006). In this paper
      we ask the question: can simple BG-mediated mechanisms account for a structured
      transition from variation to repetition, or are more sophisticated cognitive
      mechanisms always necessary? To address this question, we present a computational
      model of BG-mediated biasing of behavior. In our model, unlike most other models
      of BG function, the BG biases behavior through modulation of cortical response to
      excitation; many possible movements are represented by the cortical area; and
      excitation to the cortical area is topographically-organized. We subject the
      model to simple reaching tasks, inspired by behavioral studies, in which a
      location to which to reach must be selected. Locations within a target area
      elicit a reinforcement signal. A structured transition from variation to
      repetition emerges from simple BG-mediated biasing of cortical response to
      excitation. We show how the structured pattern influences behavior in simple and
      complicated tasks. We also present analyses that describe the structured
      transition from variation to repetition due to BG-mediated biasing and from
      biasing that would be expected from a type of cognitive biasing, allowing us to
      compare behavior resulting from these types of biasing and make connections with
      future behavioral experiments. 

PMID- 24575068
TI  - Validation of the face-name pairs task in major depression: impaired recall but
      not recognition.
AB  - Major depression can be associated with neurocognitive deficits which are
      believed in part to be related to medial temporal lobe pathology. The purpose of
      this study was to investigate this impairment using a hippocampal-dependent
      neuropsychological task. The face-name pairs task was used to assess associative
      memory functioning in 19 patients with major depression. When compared to age-sex
      and-education matched controls, patients with depression showed impaired
      learning, delayed cued-recall, and delayed free-recall. However, they also showed
      preserved recognition of the verbal and nonverbal components of this task.
      Results indicate that the face-name pairs task is sensitive to neurocognitive
      deficits in major depression. 

PMID- 24575069
TI  - "I pick you": the impact of fairness and race on infants' selection of social
      partners.
AB  - By 15 months of age infants are sensitive to violations of fairness norms as
      assessed via their enhanced visual attention to unfair versus fair outcomes in
      violation-of-expectation paradigms. The current study investigated whether 15
      month-old infants select social partners on the basis of prior fair versus unfair
      behavior, and whether infants integrate social selections on the basis of
      fairness with the race of the distributors and recipients involved in the
      exchange. Experiment 1 demonstrated that after witnessing one adult distribute
      toys to two recipients fairly (2:2 distribution), and another adult distribute
      toys to two recipients unfairly (1:3 distribution), Caucasian infants selected
      fair over unfair distributors when both distributors were Caucasian; however,
      this preference was not present when the fair actor was Asian and the unfair
      actor was Caucasian. In Experiment 2, when fairness, the race of the distributor,
      and the race of the recipients were fully crossed, Caucasian infants' social
      selections varied as a function of the race of the recipient advantaged by the
      unfair distributor. Specifically, infants were more likely to select the fair
      distributor when the unfair recipient advantaged the Asian (versus the Caucasian)
      recipient. These findings provide evidence that infants select social partners on
      the basis of prior fair behavior and that infants also take into account the race
      of distributors and recipients when making their social selections. 

PMID- 24575070
TI  - A new perceptual paradigm to investigate the visual remapping of others' tactile
      sensations onto one's own body shows "mirror touch" for the hands.
AB  - The last two decades have seen a multitude of publications showing the activation
      of an observer's somatosensory cortical system during the observation of touch on
      another person. Behavioral demonstrations of "mirror touch," however, have been
      slow in coming forward, and have so far primarily been shown as "visual remapping
      of touch" on the face. The present study uses a new paradigm to investigate the
      mirroring of others' tactile sensations: a 2-AFC task of intensity judgment for
      touch on the observer's left and right index finger pads. Observers viewed a left
      and right hand in an egocentric position, which were either touched passively
      (pencil moving to touch index finger pad) or actively sought touch (index finger
      moving to touch pencil). Touch and no-touch events for the two viewed hands were
      designed to eliminate confounding effects of spatial attention. Felt touches were
      either concurrent with viewed touch or no-touch events, or were delayed in time
      to assess potential response bias. The findings demonstrate visual remapping of
      touch for touch on the hands. If touch was shown on one of the hands only (e.g.,
      left), observers were more likely to perceive touch on the same hand (i.e., their
      own left hand) as more intense than touch on the other hand even if tactile
      intensities did not differ, compared to touch shown on both or neither hand.
      These remapping effects occurred only when viewed and felt touches were
      concurrent, they were strongly modulated by the way in which viewed touch was
      incurred, and they were more reliable for touch on the left hand. A second,
      control experiment, in which touch observation was replaced by bright dots shown
      on or next to the finger pads, confirmed that these effects were largely due to
      genuine tactile mirroring rather than to somatotopic cueing. This 2-AFC tactile
      intensity judgment task may be a useful paradigm to investigate the remapping of
      others' tactile sensations onto an observer's own body. 

PMID- 24575071
TI  - Smelly primes - when olfactory primes do or do not work.
AB  - In applied olfactory cognition the effects that olfactory stimulation can have on
      (human) behavior are investigated. To enable an efficient application of
      olfactory stimuli a model of how they may lead to a change in behavior is
      proposed. To this end we use the concept of olfactory priming. Olfactory priming
      may prompt a special view on priming as the olfactory sense has some unique
      properties which make odors special types of primes. Examples of such properties
      are the ability of odors to influence our behavior outside of awareness, to lead
      to strong affective evaluations, to evoke specific memories, and to associate
      easily and quickly to other environmental stimuli. Opportunities and limitations
      for using odors as primes are related to these properties, and alternative
      explanations for reported findings are offered. Implications for olfactory
      semantic, construal, behavior and goal priming are given based on a brief
      overview of the priming literature from social psychology and from olfactory
      perception science. We end by formulating recommendations and ideas for a future
      research agenda and applications for olfactory priming. 

PMID- 24575072
TI  - Aesthetic emotions, what are their cognitive functions?

PMID- 24575073
TI  - Intersubjectivity in schizophrenia: life story analysis of three cases.
AB  - The processes involved in schizophrenia are approached from a viewpoint of
      understanding, revealing those social elements susceptible to integration for
      psychotherapeutic purposes, as a complement to the predominant medical
      psychiatric focus. Firstly, the paper describes the patients' disturbances of
      self-experience and body alienations manifested in acute phases of schizophrenia.
      Secondly, the paper examines the patients' personal biographical milestones and
      consequently the acute episode is contextualized within the intersubjective
      scenario in which it manifested itself in each case. Thirdly, the patients' life
      stories are analyzed from a clinical psychological perspective, meaningfully
      connecting symptoms and life-world. Finally, it will be argued that the
      intersubjective dimension of the patients' life stories shed light not only on
      the interpersonal processes involved in schizophrenia but also upon the
      psychotherapeutic treatment best suited to each individual case. 

PMID- 24575074
TI  - Primed to be inflexible: the influence of set size on cognitive flexibility
      during childhood.
AB  - One of the hallmarks of human cognition is cognitive flexibility, the ability to
      adapt thoughts and behaviors according to changing task demands. Previous
      research has suggested that the number of different exemplars that must be
      processed within a task (the set size) can influence an individual's ability to
      switch flexibly between different tasks. This paper provides evidence that when
      tasks have a small set size, children's cognitive flexibility is impaired
      compared to when tasks have a large set size. This paper also offers insights
      into the mechanism by which this effect comes about. Understanding how set size
      interacts with task-switching informs the debate regarding the relative
      contributions of bottom-up priming and top-down control processes in the
      development of cognitive flexibility. We tested two accounts for the relationship
      between set size and cognitive flexibility: the (bottom-up) Stimulus-Task Priming
      account and the (top-down) Rule Representation account. Our findings offered
      support for the Stimulus-Task Priming account, but not for the Rule
      Representation account. They suggest that children are susceptible to bottom-up
      priming caused by stimulus repetition, and that this priming can impair their
      ability to switch between tasks. These findings make important theoretical and
      practical contributions to the executive function literature: theoretically, they
      show that the basic features of a task exert a significant influence on
      children's ability to flexibly shift between tasks through bottom-up priming
      effects. Practically, they suggest that children's cognitive flexibility may have
      been underestimated relative to adults', as paradigms used with children
      typically have a smaller set size than those used with adults. These findings
      also have applications in education, where they have the potential to inform
      teaching in key areas where cognitive flexibility is required, such as
      mathematics and literacy. 

PMID- 24575075
TI  - Meet the Fribbles: novel stimuli for use within behavioural research.
AB  - Clinical researchers make use of experimental models for mental disorders. In
      many cases, these models use stimuli that are relevant to the disorder under
      scrutiny, which allows one to experimentally investigate the factors that
      contribute to the development of the disorder. For example, one might use spiders
      or spider-like stimuli in the study of specific phobia. More broadly, researchers
      often make use of real-world stimuli such as images of animals, geometrical
      shapes or emotional words. However, these stimuli are often limited in their
      experimental controllability and their applicability to the disorder in question.
      We present a novel set of animal-like stimuli, called Fribbles, for use within
      behavioural research. Fribbles have desirable properties for use in research
      because they are similar to real-world stimuli, but due to their novelty,
      participants will not have had previous experience with them. They also have
      known properties that can be experimentally manipulated. We present an
      investigation into similarity between Fribbles in order to illustrate their
      utility in research that relies on comparisons between similar stimuli. Fribbles
      offer both experimental control and generalisability to the real world, although
      some consideration must be made concerning the properties that influence
      similarity between Fribbles when selecting them along a dimension of similarity. 

PMID- 24575076
TI  - Rationality and the illusion of choice.
AB  - The psychology of reasoning and decision making (RDM) shares the methodology of
      cognitive psychology in that researchers assume that participants are doing their
      best to solve the problems according to the instruction. Unlike other cognitive
      researchers, however, they often view erroneous answers evidence of irrationality
      rather than limited efficiency in the cognitive systems studied. Philosophers and
      psychologists also talk of people being irrational in a special sense that does
      not apply to other animals, who are seen as having no choice in their own
      behavior. I argue here that (a) RDM is no different from other fields of
      cognitive psychology and should be subject to the same kind of scientific
      inferences, and (b) the special human sense of irrationality derives from folk
      psychology and the illusory belief that there are conscious people in charge of
      their minds and decisions. 

PMID- 24575077
TI  - Age-related changes in attentional control across adolescence: how does this
      impact emotion regulation capacities?
AB  - This study set out to establish the novel use of the go/no-go Overlap task for
      investigating the role of attentional control capacities in the processing of
      emotional expressions across different age-groups within adolescence: at the
      onset of adolescence (11-12 year-olds) and toward the end of adolescence (17-18
      year-olds). We also looked at how attentional control in the processing of
      fearful, happy, and neutral expressions relates to individual differences in
      trait anxiety in these adolescent groups. We were able to show that younger
      adolescents, but not older adolescents had more difficulties with attention
      control in the presence of all faces, but particularly in the presence of fearful
      faces. Moreover, we found that across all groups, adolescents with higher trait
      anxiety exhibited attentional avoidance of all faces, which facilitated
      relatively better performance on the primary task. These differences in reaction
      time emerged in the context of comparable accuracy level in the primary task
      across age-groups. Our results contribute to our understanding of how attentional
      control abilities to faces but in particular fearful expressions may mature
      across adolescence. This may affect learning about the environment and the
      acquisition of behavioral response patterns in the social world. 

PMID- 24575080
TI  - Impact of elevated atmospheric O3 on the actinobacterial community structure and
      function in the rhizosphere of European beech (Fagus sylvatica L.).
AB  - Many bacteria belonging to the phylum of Actinobacteria are known as antagonists
      against phytpathogenic microbes. This study aimed to analyze the effect of ozone
      on the actinobacterial community of the rhizosphere of four years old European
      beech (Fagus sylvatica L.) trees during different time points of the vegetation
      period. Effects of ozone on the total community structure of Actinobacteria were
      studied based on the analysis of 16S rRNA gene amplicons. In addition effects of
      the ozone treatment on the diversity of potential biocontrol active
      Actionobacteria being able to produce antibiotics were characterized by using the
      type II polyketide synthases (PKS) genes as marker. Season as well as ozone
      treatments had a significant effect on parts of the actinobacterial rhizosphere
      community of European beech. However on the basis of the performed analysis, the
      diversity of Actinobacteria possessing type II PKS genes is neither affected by
      seasonal changes nor by the ozone treatments, indicating no influence of the
      investigated treatments on the biocontrol active part of the actinobacterial
      community. 

PMID- 24575078
TI  - Relation of callosal structure to cognitive abilities in temporal lobe epilepsy.
AB  - The main objective of this paper is to analyze the influence of mesial temporal
      lobe epilepsy (mTLE) on the morphology of the corpus callosum (CC) and its
      relation to cognitive abilities. More specifically, we investigated correlations
      between intellectual abilities and callosal morphology, while additionally
      exploring the modulating impact of (a) side of seizure onset (b) age of disease
      onset. For this reason a large representative sample of patients with hippocampal
      sclerosis (n = 79; 35 males; 44 females; age: 18-63 years) with disease onset
      ranging from 0 to 50 years of age, and consisting of 46 left and 33 right mTLE
      patients was recruited. Intelligence was measured using the Wechsler-Adult
      Intelligence Scale Revised. To get localizations of correlations with high
      anatomic precision, callosal morphology was examined using computational mesh
      based modeling methods, applied to anatomical brain MRI scans. Intellectual
      performance was positively associated with callosal thickness in anterior and
      midcallosal callosal regions, with anterior parts being slightly more affected by
      age of disease onset and side of seizure onset than posterior parts. Earlier age
      at onset of epilepsy was associated with lower thickness in anterior and
      midcallosal regions. In addition, laterality of seizure onset had a significant
      influence on anterior CC morphology, with left hemispheric origin having stronger
      effects. We found that in mTLE, anterior and midcallosal CC morphology are
      related to cognitive performance. The findings support recent findings of
      detrimental effects of early onset mTLE on anterior brain regions and of a
      distinct effect particularly of left mTLE on frontal lobe functioning and
      structure. The causal nature of the relationship remains an open question, i.e.,
      whether CC morphology impacts IQ development or whether IQ development impacts CC
      morphology, or both. 

PMID- 24575079
TI  - Antibiotic growth promoters enhance animal production by targeting intestinal
      bile salt hydrolase and its producers.
AB  - The growth-promoting effect of antibiotic growth promoters (AGPs) was correlated
      with the decreased activity of bile salt hydrolase (BSH), an intestinal bacteria
      produced enzyme that exerts negative impact on host fat digestion and
      utilization. Consistent with this finding, independent chicken studies have
      demonstrated that AGP usage significantly reduced population of Lactobacillus
      species, the major BSH-producers in the intestine. Recent finding also
      demonstrated that some AGPs, such as tetracycline and roxarsone, display direct
      inhibitory effect on BSH activity. Therefore, BSH is a promising microbiome
      target for developing novel alternatives to AGPs. Specifically, dietary
      supplementation of BSH inhibitor may promote host lipid metabolism and energy
      harvest, consequently enhancing feed efficiency and body weight gain in food
      animals. 

PMID- 24575081
TI  - Diversity and distribution of eukaryotic microbes in and around a brine pool
      adjacent to the Thuwal cold seeps in the Red Sea.
AB  - A hypoxic/suboxic brine pool at a depth of about 850 m was discovered near the
      Thuwal cold seeps in the Red Sea. Filled with high concentrations of hydrogen
      sulfide and ammonia, such a brine pool might limit the spread of eukaryotic
      organisms. Here, we compared the communities of the eukaryotic microbes in a
      microbial mat, sediments and water samples distributed in 7 sites within and
      adjacent to the brine pool. Taxonomic classification of the pyrosequenced 18S
      rRNA amplicon reads showed that fungi highly similar to the species identified
      along the Arabic coast were almost ubiquitous in the water and sediment samples,
      supporting their wide distribution in various environments. The microbial mat
      displayed the highest species diversity and contained grazers and a considerable
      percentage of unclassified species. Phylogeny-based methods revealed novel
      lineages representing a majority of the reads from the interface between the sea
      water and brine pool. Phylogenetic relationships with more reference sequences
      suggest that the lineages were affiliated with novel Alveolata and Euglenozoa
      inhabiting the interface where chemosynthetic prokaryotes are highly
      proliferative due to the strong chemocline and halocline. The brine sediments
      harbored abundant species highly similar to invertebrate gregarine parasites
      identified in different oxygen-depleted sediments. Therefore, the present
      findings support the uniqueness of some microbial eukaryotic groups in this cold
      seep brine system. 

PMID- 24575084
TI  - Microsporidia-nematode associations in methane seeps reveal basal fungal
      parasitism in the deep sea.
AB  - The deep sea is Earth's largest habitat but little is known about the nature of
      deep-sea parasitism. In contrast to a few characterized cases of bacterial and
      protistan parasites, the existence and biological significance of deep-sea
      parasitic fungi is yet to be understood. Here we report the discovery of a fungus
      related parasitic microsporidium, Nematocenator marisprofundi n. gen. n. sp. that
      infects benthic nematodes at methane seeps on the Pacific Ocean floor. This
      infection is species-specific and has been temporally and spatially stable over 2
      years of sampling, indicating an ecologically consistent host-parasite
      interaction. A high distribution of spores in the reproductive tracts of infected
      males and females and their absence from host nematodes' intestines suggests a
      sexual transmission strategy in contrast to the fecal-oral transmission of most
      microsporidia. N. marisprofundi targets the host's body wall muscles causing cell
      lysis, and in severe infection even muscle filament degradation. Phylogenetic
      analyses placed N. marisprofundi in a novel and basal clade not closely related
      to any described microsporidia clade, suggesting either that microsporidia
      nematode parasitism occurred early in microsporidia evolution or that host
      specialization occurred late in an ancient deep-sea microsporidian lineage. Our
      findings reveal that methane seeps support complex ecosystems involving
      interkingdom interactions between bacteria, nematodes, and parasitic fungi and
      that microsporidia parasitism exists also in the deep-sea biosphere. 

PMID- 24575083
TI  - Marine coastal sediments microbial hydrocarbon degradation processes:
      contribution of experimental ecology in the omics'era.
AB  - Coastal marine sediments, where important biological processes take place, supply
      essential ecosystem services. By their location, such ecosystems are particularly
      exposed to human activities as evidenced by the recent Deepwater Horizon
      disaster. This catastrophe revealed the importance to better understand the
      microbial processes involved on hydrocarbon degradation in marine sediments
      raising strong interests of the scientific community. During the last decade,
      several studies have shown the key role played by microorganisms in determining
      the fate of hydrocarbons in oil-polluted sediments but only few have taken into
      consideration the whole sediment's complexity. Marine coastal sediment ecosystems
      are characterized by remarkable heterogeneity, owning high biodiversity and are
      subjected to fluctuations in environmental conditions, especially to important
      oxygen oscillations due to tides. Thus, for understanding the fate of
      hydrocarbons in such environments, it is crucial to study microbial activities,
      taking into account sediment characteristics, physical-chemical factors (electron
      acceptors, temperature), nutrients, co-metabolites availability as well as
      sediment's reworking due to bioturbation activities. Key information could be
      collected from in situ studies, which provide an overview of microbial processes,
      but it is difficult to integrate all parameters involved. Microcosm experiments
      allow to dissect in-depth some mechanisms involved in hydrocarbon degradation but
      exclude environmental complexity. To overcome these lacks, strategies have been
      developed, by creating experiments as close as possible to environmental
      conditions, for studying natural microbial communities subjected to oil
      pollution. We present here a review of these approaches, their results and
      limitation, as well as the promising future of applying "omics" approaches to
      characterize in-depth microbial communities and metabolic networks involved in
      hydrocarbon degradation. In addition, we present the main conclusions of our
      studies in this field. 

PMID- 24575082
TI  - Associations and dynamics of Vibrionaceae in the environment, from the genus to
      the population level.
AB  - The Vibrionaceae, which encompasses several potential pathogens, including V.
      cholerae, the causative agent of cholera, and V. vulnificus, the deadliest
      seafood-borne pathogen, are a well-studied family of marine bacteria that thrive
      in a diverse habitats. To elucidate the environmental conditions under which
      vibrios proliferate, numerous studies have examined correlations with bulk
      environmental variables-e.g., temperature, salinity, nitrogen, and phosphate-and
      association with potential host organisms. However, how meaningful these
      environmental associations are remains unclear because data are fragmented across
      studies with variable sampling and analysis methods. Here, we synthesize findings
      about Vibrio correlations and physical associations using a framework of
      increasingly fine environmental and taxonomic scales, to better understand their
      dynamics in the wild. We first conduct a meta-analysis to determine trends with
      respect to bulk water environmental variables, and find that while temperature
      and salinity are generally strongly predictive correlates, other parameters are
      inconsistent and overall patterns depend on taxonomic resolution. Based on the
      hypothesis that dynamics may better correlate with more narrowly defined niches,
      we review evidence for specific association with plants, algae, zooplankton, and
      animals. We find that Vibrio are attached to many organisms, though evidence for
      enrichment compared to the water column is often lacking. Additionally, contrary
      to the notion that they flourish predominantly while attached, Vibrio can have,
      at least temporarily, a free-living lifestyle and even engage in massive blooms.
      Fine-scale sampling from the water column has enabled identification of such
      lifestyle preferences for ecologically cohesive populations, and future efforts
      will benefit from similar analysis at fine genetic and environmental sampling
      scales to describe the conditions, habitats, and resources shaping Vibrio
      dynamics. 

PMID- 24575086
TI  - Vibrio diversity and dynamics in the Monterey Bay upwelling region.
AB  - The Vibrionaceae (Vibrio) are a ubiquitous group of metabolically flexible marine
      bacteria that play important roles in biogeochemical cycling in the ocean.
      Despite this versatility, little is known about Vibrio diversity and abundances
      in upwelling regions. The seasonal dynamics of Vibrio populations was examined by
      analysis of 16S rRNA genes in Monterey Bay (MB), California from April 2006-April
      2008 at two long term monitoring stations, C1 and M2. Vibrio phylotypes within MB
      were diverse, with subpopulations clustering with several different cultured
      representatives including Allivibrio spp., Vibrio penaecida, and Vibrio
      splendidus as well as with many unidentified marine environmental bacterial 16S
      rRNA gene sequences. Total Vibrio population abundances, as well as abundances of
      a Vibrio sp. subpopulation (MBAY Vib7) and an Allivibrio sp. subpopulation (MBAY
      Vib4) were examined in the context of environmental parameters from mooring
      station and CTD cast data. Total Vibrio populations showed some seasonal
      variability but greater variability was observed within the two subpopulations.
      MBAY Vib4 was negatively associated with MB upwelling indices and positively
      correlated with oceanic season conditions, when upwelling winds relax and warmer
      surface waters are present in MB. MBAY Vib7 was also negatively associated with
      upwelling indices and represented a deeper Vibrio sp. population. Correlation
      patterns suggest that larger oceanographic conditions affect the dynamics of the
      populations in MB, rather than specific environmental factors. This study is the
      first to target and describe the diversity and dynamics of these natural
      populations in MB and demonstrates that these populations shift seasonally within
      the region. 

PMID- 24575085
TI  - Molecular diversity and predictability of Vibrio parahaemolyticus along the
      Georgian coastal zone of the Black Sea.
AB  - Vibrio parahaemolyticus is a leading cause of seafood-related gastroenteritis and
      is also an autochthonous member of marine and estuarine environments worldwide.
      One-hundred seventy strains of V. parahaemolyticus were isolated from water and
      plankton samples collected along the Georgian coast of the Black Sea during 28
      months of sample collection. All isolated strains were tested for presence of
      tlh, trh, and tdh. A subset of strains were serotyped and tested for additional
      factors and markers of pandemicity. Twenty-six serotypes, five of which are
      clinically relevant, were identified. Although all 170 isolates were negative for
      tdh, trh, and the Kanagawa Phenomenon, 7 possessed the GS-PCR sequence and 27 the
      850 bp sequence of V. parahaemolyticus pandemic strains. The V. parahaemolyticus
      population in the Black Sea was estimated to be genomically heterogeneous by rep
      PCR and the serodiversity observed did not correlate with rep-PCR genomic
      diversity. Statistical modeling was used to predict presence of V.
      parahaemolyticus as a function of water temperature, with strongest concordance
      observed for Green Cape site samples (Percent of total variance = 70, P < 0.001).
      Results demonstrate a diverse population of V. parahaemolyticus in the Black Sea,
      some of which carry pandemic markers, with increased water temperature correlated
      to an increase in abundance of V. parahaemolyticus. 

PMID- 24575087
TI  - The effect and role of environmental conditions on magnetosome synthesis.
AB  - Magnetotactic bacteria (MTB) are considered the model species for the controlled
      biomineralization of magnetic Fe oxide (magnetite, Fe3O4) or Fe sulfide
      (greigite, Fe3S4) nanocrystals in living organisms. In MTB, magnetic minerals
      form as membrane-bound, single-magnetic domain crystals known as magnetosomes and
      the synthesis of magnetosomes by MTB is a highly controlled process at the
      genetic level. Magnetosome crystals reveal highest purity and highest quality
      magnetic properties and are therefore increasingly sought after as novel
      nanoparticulate biomaterials for industrial and medical applications. In
      addition, "magnetofossils," have been used as both past terrestrial and potential
      Martian life biosignature. However, until recently, the general belief was that
      the morphology of mature magnetite crystals formed by MTB was largely unaffected
      by environmental conditions. Here we review a series of studies that showed how
      changes in environmental factors such as temperature, pH, external Fe
      concentration, external magnetic fields, static or dynamic fluid conditions, and
      nutrient availability or concentrations can all affect the biomineralization of
      magnetite magnetosomes in MTB. The resulting variations in magnetic nanocrystals
      characteristics can have consequence both for their commercial value but also for
      their use as indicators for ancient life. In this paper we will review the recent
      findings regarding the influence of variable chemical and physical environmental
      control factors on the synthesis of magnetosome by MTB, and address the role of
      MTB in the global biogeochemical cycling of iron. 

PMID- 24575088
TI  - Non-aflatoxigenic Aspergillus flavus to prevent aflatoxin contamination in crops:
      advantages and limitations.
AB  - Aspergillus flavus is a diverse assemblage of strains that include aflatoxin
      producing and non-toxigenic strains with cosmopolitan distribution. The most
      promising strategy currently being used to reduce preharvest contamination of
      crops with aflatoxin is to introduce non-aflatoxin (biocontrol) A. flavus into
      the crop environment. Whether or not introduction of biocontrol strains into
      agricultural fields is enough to reduce aflatoxin contamination to levels
      required for acceptance of the contaminated food as fit for consumption is still
      unknown. There is no question that biocontrol strains are able to reduce the size
      of the populations of aflatoxin-producing strains but the available data suggests
      that at most only a four- to five-fold reduction in aflatoxin contamination is
      achieved. There are many challenges facing this strategy that are both short term
      and long term. First, the population biology of A. flavus is not well understood
      due in part to A. flavus's diversity, its ability to form heterokaryotic
      reproductive forms, and its unknown ability to survive for prolonged periods
      after application. Second, biocontrol strains must be selected that are suitable
      for the environment, the type of crop, and the soil into which they will be
      introduced. Third, there is a need to guard against inadvertent introduction of
      A. flavus strains that could impose an additional burden on food safety and food
      quality, and fourth, with global warming and resultant changes in the soil
      nutrients and concomitant microbiome populations, the biocontrol strategy must be
      sufficiently flexible to adapt to such changes. Understanding genetic variation
      within strains of A. flavus is important for developing a robust biocontrol
      strategy and it is unlikely that a "one size fits all" strategy will work for
      preharvest aflatoxin reduction. 

PMID- 24575089
TI  - The agricultural antibiotic carbadox induces phage-mediated gene transfer in
      Salmonella.
AB  - Antibiotics are used for disease therapeutic or preventative effects in humans
      and animals, as well as for enhanced feed conversion efficiency in livestock.
      Antibiotics can also cause undesirable effects in microbial populations,
      including selection for antibiotic resistance, enhanced pathogen invasion, and
      stimulation of horizontal gene transfer. Carbadox is a veterinary antibiotic used
      in the US during the starter phase of swine production for improved feed
      efficiency and control of swine dysentery and bacterial swine enteritis. Carbadox
      has been shown in vitro to induce phage-encoded Shiga toxin in Shiga toxin
      producing Escherichia coli (STEC) and a phage-like element transferring
      antibiotic resistance genes in Brachyspira hyodysenteriae, but the effect of
      carbadox on prophages in other bacteria is unknown. This study examined carbadox
      exposure on prophage induction and genetic transfer in Salmonella enterica
      serovar Typhimurium, a human foodborne pathogen that frequently colonizes swine
      without causing disease. S. Typhimurium LT2 exposed to carbadox induced prophage
      production, resulting in bacterial cell lysis and release of virions that were
      visible by electron microscopy. Carbadox induction of phage-mediated gene
      transfer was confirmed by monitoring the transduction of a sodCIII::neo cassette
      in the Fels-1 prophage from LT2 to a recipient Salmonella strain. Furthermore,
      carbadox frequently induced generalized transducing phages in multidrug-resistant
      phage type DT104 and DT120 isolates, resulting in the transfer of chromosomal and
      plasmid DNA that included antibiotic resistance genes. Our research indicates
      that exposure of Salmonella to carbadox induces prophages that can transfer
      virulence and antibiotic resistance genes to susceptible bacterial hosts.
      Carbadox-induced, phage-mediated gene transfer could serve as a contributing
      factor in bacterial evolution during animal production, with prophages being a
      reservoir for bacterial fitness genes in the environment. 

PMID- 24575091
TI  - On the Role of Dendritic Cells Versus Other Cells in Inducing Protective CD8+ T
      Cell Responses.

PMID- 24575090
TI  - Stressful presentations: mild cold stress in laboratory mice influences phenotype
      of dendritic cells in naive and tumor-bearing mice.
AB  - The ability of dendritic cells (DCs) to stimulate and regulate T cells is
      critical to effective anti-tumor immunity. Therefore, it is important to fully
      recognize any inherent factors which may influence DC function under experimental
      conditions, especially in laboratory mice since they are used so heavily to model
      immune responses. The goals of this report are to 1) briefly summarize previous
      work revealing how DCs respond to various forms of physiological stress and 2) to
      present new data highlighting the potential for chronic mild cold stress inherent
      to mice housed at the required standard ambient temperatures to influence
      baseline DCs properties in naive and tumor-bearing mice. As recent data from our
      group shows that CD8(+) T cell function is significantly altered by chronic mild
      cold stress and since DC function is crucial for CD8(+) T cell activation, we
      wondered whether housing temperature may also be influencing DC function. Here we
      report that there are several significant phenotypical and functional differences
      among DC subsets in naive and tumor-bearing mice housed at either standard
      housing temperature or at a thermoneutral ambient temperature, which
      significantly reduces the extent of cold stress. The new data presented here
      strongly suggests that, by itself, the housing temperature of mice can affect
      fundamental properties and functions of DCs. Therefore differences in basal
      levels of stress due to housing should be taken into consideration when
      interpreting experiments designed to evaluate the impact of additional variables,
      including other stressors on DC function. 

PMID- 24575092
TI  - VH Replacement Footprint Analyzer-I, a Java-Based Computer Program for Analyses
      of Immunoglobulin Heavy Chain Genes and Potential VH Replacement Products in
      Human and Mouse.
AB  - VH replacement occurs through RAG-mediated secondary recombination between a
      rearranged VH gene and an upstream unrearranged VH gene. Due to the location of
      the cryptic recombination signal sequence (cRSS, TACTGTG) at the 3' end of VH
      gene coding region, a short stretch of nucleotides from the previous rearranged
      VH gene can be retained in the newly formed VH-DH junction as a "footprint" of VH
      replacement. Such footprints can be used as markers to identify Ig heavy chain
      (IgH) genes potentially generated through VH replacement. To explore the
      contribution of VH replacement products to the antibody repertoire, we developed
      a Java-based computer program, VH replacement footprint analyzer-I (VHRFA-I), to
      analyze published or newly obtained IgH genes from human or mouse. The VHRFA-1
      program has multiple functional modules: it first uses service provided by the
      IMGT/V-QUEST program to assign potential VH, DH, and JH germline genes; then, it
      searches for VH replacement footprint motifs within the VH-DH junction (N1)
      regions of IgH gene sequences to identify potential VH replacement products; it
      can also analyze the frequencies of VH replacement products in correlation with
      publications, keywords, or VH, DH, and JH gene usages, and mutation status; it
      can further analyze the amino acid usages encoded by the identified VH
      replacement footprints. In summary, this program provides a useful computation
      tool for exploring the biological significance of VH replacement products in
      human and mouse. 

PMID- 24575093
TI  - Serum microRNAs as Biomarkers of Human Lymphocyte Activation in Health and
      Disease.
AB  - Induction of the adaptive immune system is evaluated mostly by assessment of
      serum antibody titers and T lymphocyte responses in peripheral blood, although T
      and B cell activation occurs in lymphoid tissues. In recent years, the release of
      microRNAs (miRNAs) in the extra-cellular environment has been exploited to assess
      cell functions at distance via measurement of serum miRNAs. Activated lymphocytes
      release a large amount of nano-sized vesicles (exosomes), containing miRNA,
      however there are insufficient data to determine whether this phenomenon is
      reflected in modulation of serum miRNAs. Interestingly, miRNA signatures of
      CD4(+) T cell-derived exosomes are substantially different from intracellular
      miRNA signatures of the same cells. We have recently identified serum circulating
      miR-150 as a sensor of general lymphocyte activation and we strongly believe that
      miRNAs differentially released by specific CD4(+) effector T cell subsets (Th1,
      Th2, Th17, and Treg) may serve as serum biomarkers of their elicitation in
      lymphoid tissues but also in damaged tissues, potentially providing clinically
      relevant information about the nature of immune responses in health and disease. 

PMID- 24575094
TI  - Function of YY1 in Long-Distance DNA Interactions.
AB  - During B cell development, long-distance DNA interactions are needed for V(D)J
      somatic rearrangement of the immunoglobulin (Ig) loci to produce functional Ig
      genes, and for class switch recombination (CSR) needed for antibody maturation.
      The tissue-specificity and developmental timing of these mechanisms is a subject
      of active investigation. A small number of factors are implicated in controlling
      Ig locus long-distance interactions including Pax5, Yin Yang 1 (YY1), EZH2,
      IKAROS, CTCF, cohesin, and condensin proteins. Here we will focus on the role of
      YY1 in controlling these mechanisms. YY1 is a multifunctional transcription
      factor involved in transcriptional activation and repression, X chromosome
      inactivation, Polycomb Group (PcG) protein DNA recruitment, and recruitment of
      proteins required for epigenetic modifications (acetylation, deacetylation,
      methylation, ubiquitination, sumoylation, etc.). YY1 conditional knock-out
      indicated that YY1 is required for B cell development, at least in part, by
      controlling long-distance DNA interactions at the immunoglobulin heavy chain and
      Igkappa loci. Our recent data show that YY1 is also required for CSR. The
      mechanisms implicated in YY1 control of long-distance DNA interactions include
      controlling non-coding antisense RNA transcripts, recruitment of PcG proteins to
      DNA, and interaction with complexes involved in long-distance DNA interactions
      including the cohesin and condensin complexes. Though common rearrangement
      mechanisms operate at all Ig loci, their distinct temporal activation along with
      the ubiquitous nature of YY1 poses challenges for determining the specific
      mechanisms of YY1 function in these processes, and their regulation at the tissue
      specific and B cell stage-specific level. The large numbers of post-translational
      modifications that control YY1 functions are possible candidates for regulation. 

PMID- 24575097
TI  - CTCF and ncRNA Regulate the Three-Dimensional Structure of Antigen Receptor Loci
      to Facilitate V(D)J Recombination.
AB  - At both the immunoglobulin heavy and kappa light chain loci, there are >100
      functional variable (V) genes spread over >2 Mb that must move into close
      proximity in 3D space to the (D)J genes to create a diverse repertoire of
      antibodies. Similar events take place at the T cell receptor (TCR) loci to create
      a wide repertoire of TCRs. In this review, we will discuss the role of CTCF in
      forming rosette-like structures at the antigen receptor (AgR) loci, and the
      varied roles it plays in alternately facilitating and repressing V(D)J
      rearrangements. In addition, non-coding RNAs, also known as germline
      transcription, can shape the 3D configuration of the Igh locus, and presumably
      that of the other AgR loci. At the Igh locus, this could occur by gathering the
      regions being transcribed in the VH locus into the same transcription factory
      where IMU is being transcribed. Since the IMU promoter, EMU, is adjacent to the
      DJH rearrangement to which one V gene will ultimately rearrange, the process of
      germline transcription itself, prominent in the distal half of the VH locus, may
      play an important and direct role in locus compaction. Finally, we will discuss
      the impact of the transcriptional and epigenetic landscape of the Igh locus on VH
      gene rearrangement frequencies. 

PMID- 24575098
TI  - The Interplay between Daptomycin and the Immune System.
AB  - Antibiotics may have bacteriostatic or bactericidal effects but may also cause
      immunomodulation. Lipopeptides are known immunomodulators that interact with
      pattern recognition receptors such as Toll-like receptors in antigen presenting
      cells. Daptomycin is a novel lipopeptide antibiotic with a lipid moiety and
      unique structure that in the presence of divalent ions may directly interact with
      lipid membrane phospholipids, the major component of lipid membranes in immune
      cells. Daptomycin may also penetrate immune cells including neutrophils and
      macrophages. However, the possible immunomodulatory effects of daptomycin remain
      unknown. Understanding these effects is important to determine whether this agent
      can provide protection against infectious challenge through multiple mechanisms.
      Preliminary studies suggest that daptomycin may have minimal effects on cytokine
      production and may have synergistic immunomodulatory effects in combination with
      other immunomodulators. This review focuses on the hypothesis that daptomycin may
      also have immunomodulatory effects but further studies are needed to investigate
      this hypothesis. 

PMID- 24575096
TI  - Role of the Lymphotoxin/LIGHT System in the Development and Maintenance of
      Reticular Networks and Vasculature in Lymphoid Tissues.
AB  - Lymphoid organs are meeting zones where lymphocytes come together and encounter
      antigens present in the blood and lymph or as delivered by cells migrating from
      the draining tissue bed. The exquisite efficiency of this process relies heavily
      on highly specialized anatomy to direct and position the various players. Gated
      entry and exit control access to these theaters and reticular networks and
      associated chemokines guide cells into the proper sections. Lymphoid tissues are
      remarkably plastic, being able to expand dramatically and then involute upon
      resolution of the danger. All of the reticular scaffolds and vascular and
      lymphatic components adapt accordingly. As such, the lymph node (LN) is a
      wonderful example of a physiologic remodeling process and is potentially a guide
      to study such elements in pathological settings such as fibrosis, chronic
      infection, and tumor metastasis. The lymphotoxin/LIGHT axis delivers critical
      differentiation signals that direct and hone differentiation of both reticular
      networks and the vasculature. Considerable progress has been made recently in
      understanding the mesenchymal differentiation pathways leading to these
      specialized networks and in the remodeling that occurs in reactive LNs. In this
      article, we will review some new advances in the area in terms of developmental,
      differentiation, and maintenance events mediated by this axis. 

PMID- 24575099
TI  - Are pregnant women with chronic helminth infections more susceptible to
      congenital infections?

PMID- 24575095
TI  - Regulatory T cells as immunotherapy.
AB  - Regulatory T cells (Tregs) suppress exuberant immune system activation and
      promote immunologic tolerance. Because Tregs modulate both innate and adaptive
      immunity, the biomedical community has developed an intense interest in using
      Tregs for immunotherapy. Conditions that require clinical tolerance to improve
      outcomes - autoimmune disease, solid organ transplantation, and hematopoietic
      stem cell transplantation - may benefit from Treg immunotherapy. Investigators
      have designed ex vivo strategies to isolate, preserve, expand, and infuse Tregs.
      Protocols to manipulate Treg populations in vivo have also been considered.
      Barriers to clinically feasible Treg immunotherapy include Treg stability, off
      cell effects, and demonstration of cell preparation purity and potency. Clinical
      trials involving Treg adoptive transfer to treat graft versus host disease
      preliminarily demonstrated the safety and efficacy of Treg immunotherapy in
      humans. Future work will need to confirm the safety of Treg immunotherapy and
      establish the efficacy of specific Treg subsets for the treatment of immune
      mediated disease. 

PMID- 24575100
TI  - Natural killer cells and neuroblastoma: tumor recognition, escape mechanisms, and
      possible novel immunotherapeutic approaches.
AB  - Neuroblastoma (NB) is the most common extra-cranial solid tumor of childhood and
      arises from developing sympathetic nervous system. Most primary tumors localize
      in the abdomen, the adrenal gland, or lumbar sympathetic ganglia. Amplification
      in tumor cells of MYCN, the major oncogenic driver, patients' age over 18 months,
      and the presence at diagnosis of a metastatic disease (stage IV, M) identify NB
      at high risk of treatment failure. Conventional therapies did not significantly
      improve the overall survival of these patients. Moreover, the limited landscape
      of somatic mutations detected in NB is hampering the development of novel
      pharmacological approaches. Major efforts aim to identify novel NB-associated
      surface molecules that activate immune responses and/or direct drugs to tumor
      cells and tumor-associated vessels. PVR (Poliovirus Receptor) and B7-H3 are
      promising targets, since they are expressed by most high-risk NB, are upregulated
      in tumor vasculature and are essential for tumor survival/invasiveness. PVR is a
      ligand of DNAM-1 activating receptor that triggers the cytolytic activity of
      natural killer (NK) cells against NB. In animal models, targeting of PVR with an
      attenuated oncolytic poliovirus induced tumor regression and elimination. Also B7
      H3 was successfully targeted in preclinical studies and is now being tested in
      phase I/II clinical trials. B7-H3 down-regulates NK cytotoxicity, providing NB
      with a mechanism of escape from immune response. The immunosuppressive potential
      of NB can be enhanced by the release of soluble factors that impair NK cell
      function and/or recruitment. Among these, TGF-beta1 modulates the cytotoxicity
      receptors and the chemokine receptor repertoire of NK cells. Here, we summarize
      the current knowledge on the main cell surface molecules and soluble mediators
      that modulate the function of NK cells in NB, considering the pros and cons that
      must be taken into account in the design of novel NK cell-based immunotherapeutic
      approaches. 

PMID- 24575101
TI  - Origin and evolution of metal P-type ATPases in Plantae (Archaeplastida).
AB  - Metal ATPases are a subfamily of P-type ATPases involved in the transport of
      metal cations across biological membranes. They all share an architecture
      featuring eight transmembrane domains in pairs of two and are found in
      prokaryotes as well as in a variety of Eukaryotes. In Arabidopsis thaliana, eight
      metal P-type ATPases have been described, four being specific to copper transport
      and four displaying a broader metal specificity, including zinc, cadmium, and
      possibly copper and calcium. So far, few efforts have been devoted to elucidating
      the origin and evolution of these proteins in Eukaryotes. In this work, we use
      large-scale phylogenetics to show that metal P-type ATPases form a homogenous
      group among P-type ATPases and that their specialization into either monovalent
      (Cu) or divalent (Zn, Cd...) metal transport stems from a gene duplication that
      took place early in the evolution of Life. Then, we demonstrate that the four
      subgroups of plant metal ATPases all have a different evolutionary origin and a
      specific taxonomic distribution, only one tracing back to the cyanobacterial
      progenitor of the chloroplast. Finally, we examine the subsequent evolution of
      these proteins in green plants and conclude that the genes thoroughly
      characterized in model organisms are often the result of lineage-specific gene
      duplications, which calls for caution when attempting to infer function from
      sequence similarity alone in non-model organisms. 

PMID- 24575102
TI  - Regulation of primary plant metabolism during plant-pathogen interactions and its
      contribution to plant defense.
AB  - Plants are constantly exposed to microorganisms in the environment and, as a
      result, have evolved intricate mechanisms to recognize and defend themselves
      against potential pathogens. One of these responses is the downregulation of
      photosynthesis and other processes associated with primary metabolism that are
      essential for plant growth. It has been suggested that the energy saved by
      downregulation of primary metabolism is diverted and used for defense responses.
      However, several studies have shown that upregulation of primary metabolism also
      occurs during plant-pathogen interactions. We propose that upregulation of
      primary metabolism modulates signal transduction cascades that lead to plant
      defense responses. In support of this thought, we here compile evidence from the
      literature to show that upon exposure to pathogens or elicitors, plants induce
      several genes associated with primary metabolic pathways, such as those involved
      in the synthesis or degradation of carbohydrates, amino acids and lipids. In
      addition, genetic studies have confirmed the involvement of these metabolic
      pathways in plant defense responses. This review provides a new perspective
      highlighting the relevance of primary metabolism in regulating plant defense
      against pathogens with the hope to stimulate further research in this area. 

PMID- 24575104
TI  - Many rivers to cross: the journey of zinc from soil to seed.
AB  - An important goal of micronutrient biofortification is to enhance the amount of
      bioavailable zinc in the edible seed of cereals and more specifically in the
      endosperm. The picture is starting to emerge for how zinc is translocated from
      the soil through the mother plant to the developing seed. On this journey, zinc
      is transported from symplast to symplast via multiple apoplastic spaces. During
      each step, zinc is imported into a symplast before it is exported again. Cellular
      import and export of zinc requires passage through biological membranes, which
      makes membrane-bound transporters of zinc especially interesting as potential
      transport bottlenecks. Inside the cell, zinc can be imported into or exported out
      of organelles by other transporters. The function of several membrane proteins
      involved in the transport of zinc across the tonoplast, chloroplast or plasma
      membranes are currently known. These include members of the ZIP (ZRT-IRT-like
      Protein), and MTP (Metal Tolerance Protein) and heavy metal ATPase (HMA)
      families. An important player in the transport process is the ligand
      nicotianamine that binds zinc to increase its solubility in living cells and in
      this way buffers the intracellular zinc concentration. 

PMID- 24575103
TI  - Root traits and microbial community interactions in relation to phosphorus
      availability and acquisition, with particular reference to Brassica.
AB  - Brassicas are among the most widely grown and important crops worldwide.
      Phosphorus (P) is a key mineral element in the growth of all plants and is
      largely supplied as inorganic rock-phosphate, a dwindling resource, which is
      likely to be an increasingly significant factor in global agriculture. In order
      to develop crops which can abstract P from the soil, utilize it more efficiently,
      require less of it or obtain more from other sources such as soil organic P
      reservoirs, a detailed understanding the factors that influence P metabolism and
      cycling in plants and associated soil is required. This review focuses on the
      current state of understanding of root traits, rhizodeposition and rhizosphere
      community interaction as it applies to P solubilization and acquisition, with
      particular reference to Brassica species. Physical root characteristics,
      exudation of organic acids (particularly malate and citrate) and phosphatase
      enzymes are considered and the potential mechanisms of control of these responses
      to P deficiency examined. The influence of rhizodeposits on the development of
      the rhizosphere microbial community is discussed and the specific features of
      this community in response to P deficiency are considered; specifically
      production of phosphatases, phytases and phosphonate hydrolases. Finally various
      potential approaches for improving overall P use efficiency in Brassica
      production are discussed. 

PMID- 24575105
TI  - Evolutionary aspects of non-cell-autonomous regulation in vascular plants:
      structural background and models to study.
AB  - Plasmodesmata (PD) serve for the exchange of information in form of miRNA,
      proteins, and mRNA between adjacent cells in the course of plant development.
      This fundamental role of PD is well established in angiosperms but has not yet
      been traced back to the evolutionary ancient plant taxa where functional studies
      lag behind studies of PD structure and ontogenetic origin. There is convincing
      evidence that the ability to form secondary (post-cytokinesis) PD, which can
      connect any adjacent cells, contrary to primary PD which form during cytokinesis
      and link only cells of the same lineage, appeared in the evolution of higher
      plants at least twice: in seed plants and in some representatives of the
      Lycopodiophyta. The (in)ability to form secondary PD is manifested in the
      symplasmic organization of the shoot apical meristem (SAM) which in most taxa of
      seedless vascular plants differs dramatically from that in seed plants.
      Lycopodiophyta appear to be suitable models to analyze the transport of
      developmental regulators via PD in SAMs with symplasmic organization both
      different from, as well as analogous to, that in angiosperms, and to understand
      the evolutionary aspects of the role of this transport in the morphogenesis of
      vascular plant taxa. 

PMID- 24575106
TI  - The RTR complex as caretaker of genome stability and its unique meiotic function
      in plants.
AB  - The RTR complex consisting of a RecQ helicase, a type IA topoisomerase and the
      structural protein RMI1 is involved in the processing of DNA recombination
      intermediates in all eukaryotes. In Arabidopsis thaliana the complex partners
      RECQ4A, topoisomerase 3alpha and RMI1 have been shown to be involved in DNA
      repair and in the suppression of homologous recombination in somatic cells.
      Interestingly, mutants of AtTOP3A and AtRMI1 are also sterile due to extensive
      chromosome breakage in meiosis I, a phenotype that seems to be specific for
      plants. Although both proteins are essential for meiotic recombination it is
      still elusive on what kind of intermediates they are acting on. Recent data
      indicate that the pattern of non-crossover (NCO)-associated meiotic gene
      conversion (GC) differs between plants and other eukaryotes, as less NCOs in
      comparison to crossovers (CO) could be detected in Arabidopsis. This indicates
      that NCOs happen either more rarely in plants or that the conversion tract length
      is significantly shorter than in other organisms. As the TOP3alpha/RMI1-mediated
      dissolution of recombination intermediates results exclusively in NCOs, we
      suggest that the peculiar GC pattern found in plants is connected to the unique
      role, members of the RTR complex play in plant meiosis. 

PMID- 24575107
TI  - The SPI-1-like Type III secretion system: more roles than you think.
AB  - The type III secretion system (T3SS) is a protein delivery system which is
      involved in a wide spectrum of interactions, from mutualism to pathogenesis,
      between Gram negative bacteria and various eukaryotes, including plants, fungi,
      protozoa and mammals. Various phylogenetic families of the T3SS have been
      described, including the Salmonella Pathogenicity Island 1 family (SPI-1). The
      SPI-1 T3SS was initially associated with the virulence of enteric pathogens, but
      is actually found in a diverse array of bacterial species, where it can play
      roles in processes as different as symbiotic interactions with insects and
      colonization of plants. We review the multiple roles of the SPI-1 T3SS and
      discuss both how these discoveries are changing our perception of the SPI-1
      family and what impacts this has on our understanding of the specialization of
      the T3SS in general. 

PMID- 24575109
TI  - Low-density lipoprotein and intracerebral hematoma expansion in daily alcohol
      users.
AB  - BACKGROUND: Epidemiological studies suggest that the intracerebral hemorrhage
      (ICH) rate correlates with alcohol consumption. Alcohol leads to elevated blood
      pressure (BP) and inhibition of platelet aggregation. These factors could promote
      excessive bleeding. To our knowledge, in the setting of normal liver function
      tests, there are no studies that have systematically evaluated the relationship
      between daily alcohol use and hematoma expansion. The aim of this study is to
      compare the baseline ICH characteristics, frequency of hematoma expansion, and
      outcomes in patients with ICH who are daily alcohol users with those who are not
      daily alcohol users. METHODS: A retrospective chart review was performed on
      consecutive patients who presented from July 2008 to July 2013 to the Tulane
      University Hospital in New Orleans, La., USA, with a spontaneous ICH. Ninety-nine
      patients who met these criteria were admitted. Patients who underwent hematoma
      evacuation were excluded. Hemorrhage volumes were calculated based on the ABC/2
      method. Low-density lipoprotein (LDL) was dichotomized into low (<100 mg/dl) and
      high (>=100 mg/dl) values. Comparisons were made using t tests, chi(2) and
      nonparametric equivalents where appropriate. ICH growth in 24 h and LDL were
      evaluated using linear regression. RESULTS: Of the 226 patients who met inclusion
      criteria, 20.4% had a history of daily alcohol use. The average age was 61 years
      (range 19-94), 55.6% of the patients were males, and 67.1% were of African
      American origin. Daily alcohol use was associated with male gender, lower rate of
      home antihypertensive, higher presenting BP, and lower platelet counts, but there
      was no difference in ICH characteristics, ICH growth, or clinical outcome. Daily
      alcohol use in patients with a low LDL level was associated with supratentorial
      location and trends for lower baseline Glasgow Coma Scale score, higher ICH
      score, and follow-up ICH volume, but no significant difference in significant
      hematoma expansion or clinical outcome except for a trend for higher mortality
      was found (25 vs. 9.5%, p = 0.1311) compared to patients with high LDL values.
      CONCLUSIONS: Our data suggest that neither chronic daily alcohol use nor a low
      LDL level in combination with daily alcohol use can be used to predict ICH
      growth. Daily alcohol use was associated with untreated hypertension and higher
      BP on presentation. A low LDL level in combination with daily alcohol use may be
      linked with larger and more severe ICH, but we were unable to demonstrate a
      relationship with hematoma expansion or poor clinical outcome. The role of LDL in
      vessel fragility and clot stabilization needs to be further explored before
      concluding that a low LDL level confers risk of bleeding.

PMID- 24575110
TI  - Short-term changes in ambient temperature and risk of ischemic stroke.
AB  - BACKGROUND: Despite consistent evidence of a higher short-term risk of
      cardiovascular mortality associated with ambient temperature, there have been
      discrepant findings on the association between temperature and ischemic stroke.
      Moreover, few studies have considered potential confounding by ambient fine
      particulate matter air pollution <2.5 MUm in diameter (PM2.5) and none have
      examined the impact of temperature changes on stroke in the subsequent hours
      rather than days. The aim of this study was to evaluate whether changes in
      temperature trigger an ischemic stroke in the following hours and days and
      whether humid days are particularly harmful. METHODS: We reviewed the medical
      records of 1,705 patients residing in the metropolitan region of Boston, Mass.,
      USA, who were hospitalized with neurologist-confirmed ischemic stroke, and we
      abstracted data on the time of symptom onset and clinical characteristics. We
      obtained hourly meteorological data from the National Weather Service station and
      hourly PM2.5 data from the Harvard ambient monitoring station. We used the time
      stratified case-crossover design to assess the association between ischemic
      stroke and apparent temperature averaged over 1-7 days prior to stroke onset
      adjusting for PM2.5. We assessed whether differences in apparent temperature
      trigger a stroke within shorter time periods by examining the association between
      stroke onset and apparent temperature levels averaged in 2-hour increments prior
      to stroke onset (0-2 h through 36-38 h). We tested whether the association varied
      by health characteristics or by PM2.5, ozone or relative humidity. RESULTS: The
      incidence rate ratio of ischemic stroke was 1.09 (95% confidence interval 1.01
      1.18) following a 5 degrees C decrement in average apparent temperature over the
      2 days preceding symptom onset. The higher risk associated with cooler
      temperatures peaked in the first 14-34 h. There was no statistically significant
      difference in the association between temperature and ischemic stroke across
      seasons. The risk of ischemic stroke was not meaningfully different across
      subgroups of patients defined by health characteristics. The association between
      ischemic stroke and ambient temperature was stronger on days with higher levels
      of relative humidity. CONCLUSIONS: Lower temperatures are associated with a
      higher risk of ischemic stroke onset in both warm and cool seasons, and the risk
      is higher on days with higher levels of relative humidity. Based on this study
      and the body of literature on ambient temperature and cardiovascular events,
      identifying methods for mitigating cardiovascular risk may be warranted.

PMID- 24575108
TI  - Drying without senescence in resurrection plants.
AB  - Research into extreme drought tolerance in resurrection plants using species such
      as Craterostigma plantagineum, C. wilmsii, Xerophyta humilis, Tortula ruralis,
      and Sporobolus stapfianus has provided some insight into the desiccation
      tolerance mechanisms utilized by these plants to allow them to persist under
      extremely adverse environmental conditions. Some of the mechanisms used to ensure
      cellular preservation during severe dehydration appear to be peculiar to
      resurrection plants. Apart from the ability to preserve vital cellular components
      during drying and rehydration, such mechanisms include the ability to down
      regulate growth-related metabolism rapidly in response to changes in water
      availability, and the ability to inhibit dehydration-induced senescence programs
      enabling reconstitution of photosynthetic capacity quickly following a rainfall
      event. Extensive research on the molecular mechanism of leaf senescence in non
      resurrection plants has revealed a multi-layered regulatory network operates to
      control programed cell death pathways. However, very little is known about the
      molecular mechanisms that resurrection plants employ to avoid undergoing drought
      related senescence during the desiccation process. To survive desiccation,
      dehydration in the perennial resurrection grass S. stapfianus must proceed slowly
      over a period of 7 days or more. Leaves detached from the plant before 60%
      relative water content (RWC) is attained are desiccation-sensitive indicating
      that desiccation tolerance is conferred in vegetative tissue of S. stapfianus
      when the leaf RWC has declined to 60%. Whilst some older leaves remaining
      attached to the plant during dehydration will senesce, suggesting dehydration
      induced senescence may be influenced by leaf age or the rate of dehydration in
      individual leaves, the majority of leaves do not senesce. Rather these leaves
      dehydrate to air-dryness and revive fully following rehydration. Hence it seems
      likely that there are genes expressed in younger leaf tissues of resurrection
      plants that enable suppression of drought-related senescence pathways. As very
      few studies have directly addressed this phenomenon, this review aims to discuss
      current literature surrounding the activation and suppression of senescence
      pathways and how these pathways may differ in resurrection plants. 

PMID- 24575111
TI  - Vascular pathology in the extracranial vertebral arteries in patients with acute
      ischemic stroke.
AB  - INTRODUCTION: Vascular pathology in the extracranial vertebral arteries remains
      among the possible causes in cryptogenic stroke. However, the diagnosis is
      challenged by the great variety in the anatomy of the vertebral arteries,
      clinical symptoms and difficulties in the radiological assessments. The aim of
      this study was to assess the prevalence of CT angiography (CTA)-detected
      pathological findings in the extracranial vertebral arteries in an acute stroke
      population and secondly to determine the frequency of posterior pathology as
      probable cause in patients with otherwise cryptogenic stroke. METHOD: The
      analysis was based on 657 consecutive patients with symptoms of acute stroke and
      a final diagnosis of ischemic stroke or transient ischemic attack. On admission,
      a noncontrast CT cerebrum and CTA were performed. A senior consultant
      neuroradiologist, blinded to clinical data, reviewed all CTA scans
      systematically, assessing the four segments of the extracranial vertebral
      arteries. First, the frequency of pathological findings including stenosis,
      plaques, dissection, kinked artery and coiling was assessed. Subsequently, we
      explored the extent of the pathological findings that were the most plausible
      causes of stroke, namely either a possible dissection or a kinked artery.
      RESULTS: Findings in the extracranial vertebral arteries included significant
      stenosis (0.8%), atherosclerotic plaque types (3.8%), possible dissections
      (2.6%), kinked arteries (2.6%) and coiling (32.0%). Eighteen patients (2.8%) with
      pathological findings had an unknown cause of stroke, likely posterior symptoms
      and no clinical stroke symptoms from the anterior circuit. Of these, 3 cases were
      kinked arteries (0.5%) and 15 cases (2.3%) were possible dissections. CONCLUSION:
      We found that in approximately 3% of the study population, the most plausible
      cause of the cryptogenic strokes was due to a pathological finding in the
      posterior extracranial vertebral arteries, being either a possible dissection or
      a kinked artery. In general, posterior vascular pathology is not uncommon, and
      CTA is a useful modality in the detection of changes based on characteristics and
      locations of findings in the extracranial vertebral arteries. Ultrasound
      examination can be a useful supplementary tool in deciding the consequence of
      vascular findings on CTA.

PMID- 24575113
TI  - Association between the COMTVal158Met Genotype and Alzheimer's Disease in the Han
      Chinese Population.
AB  - BACKGROUND: Alzheimer's disease (AD) is the leading cause of dementia worldwide
      and is associated with individual, familial and social burdens. Catechol-O
      methyltransferase (COMT) may have a prominent role in AD pathophysiology by
      affecting the metabolism of catecholamine neurotransmitters and estrogen.
      Although the COMT rs4680 gene polymorphism has been investigated as a
      susceptibility factor for AD, the results are inconsistent. The aim of this study
      was to examine the influence of the COMT rs4680 gene polymorphism as a risk
      factor for AD in the Han Chinese population and its synergistic effect with the
      apolipoprotein E (APOE)gene. METHODS: A total of 137 AD patients and 194 healthy
      controls were analyzed. Clinical criteria and neuropsychological tests were used
      to establish diagnostic groups. All subjects were analyzed for the COMTrs4680
      polymorphism and APOEgenotype. RESULTS: No significant differences were observed
      between AD and control subjects regarding the COMT genotype frequencies of
      Val/Val, Val/Met and Met/Met, but Met alleles were higher in AD than in control
      subjects (35.4 and 28.1%, p = 0.045). A minor synergistic effect between the
      genotypes GG and APOEepsilon4 was observed in AD patients (OR: 5.707, 95% CI:
      2.505-13.002, p < 0.001). This synergistic effect was greater in women, who
      showed higher OR of AD (16.007, 95% CI: 4.606-56.118, p < 0.001) versus the AD
      group with APOE epsilon4 (11.972, 95% CI: 5.534-25.902, p < 0.001). Furthermore,
      the COMT Met allele was an independent risk factor for AD without APOE epsilon4
      allele carriers (OR: 1.806, 95% CI: 1.160-2.810, p = 0.009), especially in men
      (OR: 4.904, 95% CI: 2.381-10.099, p < 0.001). CONCLUSION: The COMT(Val158Met)
      polymorphism is not an independent risk factor for AD but shows a synergistic
      effect between the genotypes GG and APOEepsilon4 that proves greater in women
      with AD. The COMT Met allele represents a risk factor in AD without APOE epsilon4
      allele carriers, which is notable in men with AD.

PMID- 24575112
TI  - Cognitive Impairment Assessment through Visuospatial Memory Can Be Performed with
      a Modified Walking Corsi Test Using the 'Magic Carpet'.
AB  - BACKGROUND: Subjects with mild cognitive impairment (MCI) have disturbances in
      their spatial navigation abilities and exhibit early deficits in visuospatial
      short-term memory. The purpose of the present study was to determine whether a
      quantitative (span score) and qualitative (evaluating navigation strategies used)
      analysis of the Corsi test (usual condition and complex navigation task) would be
      useful to reveal cognitive decline. METHODS: We evaluated the performance of 15
      young adults, 21 healthy elderly subjects and 15 subjects with MCI using the
      electronic version of the Corsi test (the Modified Corsi Block-Tapping Test,
      MCBT) and the complex navigation task (the Modified Walking Corsi Test, MWCT).
      The MWCT, which is an adaptation of the Corsi test, assesses spatial memory when
      the subject walks in a complex environment. We used Richard et al.'s model [Cogn
      Sci 1993;17:497-529] to investigate problem-solving strategies during the Corsi
      tests. RESULTS: The span scores obtained on the MCBT and the MWCT were
      significantly lower in the healthy elderly subjects (MCBT = 5.0 +/- 0.7; MWCT =
      4.0 +/- 0.7) and the subjects with MCI (MCBT = 4.7 +/- 0.8; MWCT = 4.1 +/- 0.9)
      than in the younger adults (MCBT = 6.2 +/- 0.6; MWCT = 5.3 +/- 1.0). The
      visuospatial working memory was more impaired in the complex navigation task
      (MWCT = 4.3 +/- 0.9) than in the modified Corsi test (MCBT = 5.3 +/- 0.8).
      Finally, the subjects with greater cognitive impairment were more likely to have
      inadequate or absence of problem-solving strategies. CONCLUSIONS: Investigating
      the problem-solving strategies used during the MWCT appears to be a promising way
      to differentiate between the subjects with MCI and the healthy elderly subjects.

PMID- 24575114
TI  - Postural stability analysis with inertial measurement units in Alzheimer's
      disease.
AB  - BACKGROUND: The cause of frequent falls in patients with Alzheimer's disease (AD)
      is still not well understood. Nevertheless, balance control and sensory
      organization are known to be critical for moving safely and adapting to the
      environment. METHODS: We evaluated postural stability in 20 AD patients (11
      fallers and 9 nonfallers) and 16 healthy controls with an inertial measurement
      unit (triaxial accelerometers and gyroscopes) attached to the center of mass
      (COM) in different balance conditions (Romberg on flat surface and
      frontward/backward-inclined surface, with or without visual suppression) in a
      motor lab. RESULTS: In AD patients, the group of fallers showed a different
      kinetic pattern of postural stability characterized by higher vulnerability to
      visual suppression, higher total/maximal displacement and a
      mediolateral/anteroposterior range of sway, and a consequent need for more
      corrections of COM pitch and roll angles. CONCLUSION: Further studies are needed
      to consolidate the normative values of the discriminatory kinetic variables with
      the potential of inclusion in a multifactorial analysis of the risk of falls.
      Nevertheless, these results highlight signs of impairment of central postural
      control in AD, which may require early therapeutic intervention.

PMID- 24575116
TI  - Rapidly progressive lupus nephritis with extremely high levels of antineutrophil
      cytoplasmic antibodies.
AB  - A 43-year-old woman, with a 3-month history of fatigue, anaemia and swollen lymph
      nodes, underwent biopsy of a lymph node, which revealed reactive lymphadenopathy.
      Due to an increased serum creatinine concentration and severe proteinuria, a
      kidney biopsy was performed, which revealed diffuse, segmental, proliferative,
      immune-complex glomerulonephritis with crescents. Electron microscopy showed
      tubulo-reticular structures within one endothelial cell. These were a typical
      clinical presentation and compatible histopathological findings for systemic
      lupus erythematosus; however, the anti-myeloperoxidase antineutrophil cytoplasmic
      antibody (MPO-ANCA) level was extraordinarily high. In spite of treatment with
      intravenous cyclophosphamide and methylprednisolone pulse therapy, the patient's
      kidney function declined. Starting plasma exchange improved her renal function
      and removed MPO-ANCAs, which were suspected to play the major role in the
      pathogenesis of glomerulonephritis. These findings indicate that in addition to
      lupus nephritis, MPO-ANCAs may be involved in the pathogenesis of
      glomerulonephritis and that the coincidence of systemic lupus erythematosus and
      ANCA may be responsible for the severe clinical course in our patient. 

PMID- 24575115
TI  - Optimizing evaluation of split renal function in a living kidney donor using
      scintigraphy and calculation of the geometric mean: a case report.
AB  - Within the evaluation process of living kidney donors, split renal function is
      usually evaluated by renal scintigraphy. Since split renal function measured by
      conventional posterior scans depends on the position of the kidney, actual
      suitable donors may be rejected because of an inaccurate examination technique.
      We report the case of a 28-year-old male living kidney donor. Due to a complex
      vascular anatomy of the right kidney, only his left kidney was considered
      eligible for transplantation. In conventional posterior Tc99m-mercapto
      acetyltriglycine scintigraphy, the left kidney had a relative function of 60%. A
      second scintigraphy using anterior and posterior dimercaptosuccinic acid scans
      with calculation of the geometric mean showed an adapted relative function of the
      left kidney of 53%, now meeting the inclusion criteria for living kidney
      donation. This case shows that the geometric mean method using simultaneous
      anterior and posterior views obtained with a dual-head gamma camera can be a very
      helpful approach to determine split renal function of potential living kidney
      donors. Further investigation is necessary to prove the benefit of a general
      bilateral scan before living kidney donation. 

PMID- 24575117
TI  - Revision of perineal urethrostomy using a meshed split-thickness skin graft.
AB  - Perineal urethrostomy is considered to be the last option to restore voiding in
      complex/recurrent urethral stricture disease. It is also a necessary procedure
      after penectomy or urethrectomy. Stenosis of the perineal urethrostomy has been
      reported in up to 30% of cases. There is no consensus on how to treat a stenotic
      perineal urethrostomy, but, in general, a form of urinary diversion is offered to
      the patient. We present the case of a young male who underwent perineal
      urethrostomy after urethrectomy for urethral cancer. The postoperative period was
      complicated by wound dehiscence with subsequent complete obliteration of the
      perineal urethrostomy. Revision surgery was performed with reopening of the
      obliterated urethral stump and coverage of the skin defect between the urethra
      and the perineal/scrotal skin with a meshed split-thickness skin graft. To date,
      this patient is voiding well and satisfied with the offered solution. 

PMID- 24575118
TI  - Interferon-gamma Reduces the Proliferation of Primed Human Renal Tubular Cells.
AB  - BACKGROUND/AIMS: Chronic kidney disease (CKD) is a progressive deterioration of
      the kidney function, which may eventually lead to renal failure and the need for
      dialysis or kidney transplant. Whether initiated in the glomeruli or the tubuli,
      CKD is characterized by progressive nephron loss, for which the process of
      tubular deletion is of key importance. Tubular deletion results from tubular
      epithelial cell death and defective repair, leading to scarring of the renal
      parenchyma. Several cytokines and signaling pathways, including transforming
      growth factor-beta (TGF-beta) and the Fas pathway, have been shown to participate
      in vivo in tubular cell death. However, there is some controversy about their
      mode of action, since a direct effect on normal tubular cells has not been
      demonstrated. We hypothesized that epithelial cells would require specific
      priming to become sensitive to TGF-beta or Fas stimulation and that this priming
      would be brought about by specific mediators found in the pathological scenario.
      METHODS: Herein we studied whether the combined effect of several stimuli known
      to take part in CKD progression, namely TGF-beta, tumor necrosis factor-alpha,
      interferon-gamma (IFN-gamma), and Fas stimulation, on primed resistant human
      tubular cells caused cell death or reduced proliferation. RESULTS: We demonstrate
      that these cytokines have no synergistic effect on the proliferation or viability
      of human kidney (HK2) cells. We also demonstrate that IFN-gamma, but not the
      other stimuli, reduces the proliferation of cycloheximide-primed HK2 cells
      without affecting their viability. CONCLUSION: Our results point at a potentially
      important role of IFN-gamma in defective repair, leading to nephron loss during
      CKD.

PMID- 24575119
TI  - Second-line immunosuppressive treatment of childhood nephrotic syndrome: a single
      center experience.
AB  - OBJECTIVE: Most cases of idiopathic nephrotic syndrome in childhood are
      responsive to corticosteroids. However, there is a small group of children that
      demonstrate steroid resistance (steroid-resistant nephrotic syndrome; SRNS),
      steroid dependence, or that frequently relapse (frequent-relapse steroid
      sensitive nephrotic syndrome; FR-SSNS) which are more clinically difficult to
      treat. Therefore, second-line immunosuppressants, such as alkylating agents,
      calcineurin inhibitors, antimetabolites and, more recently, rituximab, have been
      used with varying success. The objective was to evaluate the response rates of
      various second-line therapies in the treatment of childhood nephrotic syndrome.
      STUDY DESIGN: A retrospective chart review of pediatric subjects with idiopathic
      nephrotic syndrome was conducted at a single tertiary care center (2007-2012).
      Drug responses were classified as complete response, partial response, and no
      response. RESULTS: Of the 188 charts reviewed, 121 children were classified as
      SSNS and 67 children as SRNS; 58% were classified as FR-SSNS. Sixty-five subjects
      were diagnosed with focal segmental glomerulosclerosis via biopsy. Follow-up
      ranged from 6 months to 21 years. The combined rate of complete and partial
      response for mycophenolate mofetil (MMF) was 65% (33/51) in SSNS and 67% (6/9) in
      SRNS. For tacrolimus, the response rate was 96% (22/23) for SSNS and 77% (17/22)
      for SRNS. Eighty-three percent (5/6) of SSNS subjects treated with rituximab went
      into complete remission; 60% relapsed after B-cell repletion. Eight refractory
      subjects were treated with combined MMF/tacrolimus/corticosteroid therapy with a
      75% response rate. CONCLUSION: Our experience demonstrates that older medications
      can be replaced with newer ones such as MMF, tacrolimus, and rituximab with good
      outcomes and better side effect profiles. The treatment of refractory cases with
      combination therapy is promising.

PMID- 24575120
TI  - Evolutionary diversifications of plants on the Qinghai-Tibetan Plateau.
AB  - The Qinghai-Tibetan Plateau (QTP) is the highest and one of the most extensive
      plateaus in the world. Phylogenetic, phylogeographic, and ecological studies
      support plant diversifications on the QTP through multiple mechanisms such as
      allopatric speciation via geographic isolation, climatic oscillations and
      divergences, pollinator-mediated isolation, diploid hybridization and
      introgression, and allopolyploidy. These mechanisms have driven spectacular
      radiations and/or species diversifications in various groups of plants such as
      Pedicularis L., Saussurea DC., Rhododendron L., Primula L., Meconopsis Vig.,
      Rhodiola L., and many lineages of gymnosperms. Nevertheless, much work is needed
      toward understanding the evolutionary mechanisms of plant diversifications on the
      QTP. Well-sampled biogeographic analyses of the QTP plants in the broad framework
      of the Northern Hemisphere as well as the Southern Hemisphere are still
      relatively few and should be encouraged in the next decade. This paper reviews
      recent evidence from phylogenetic and biogeographic studies in plants, in the
      context of rapid radiations, mechanisms of species diversifications on the QTP,
      and the biogeographic significance of the QTP in the broader context of both the
      Northern and Southern Hemisphere biogeography. Integrative multidimensional
      analyses of phylogeny, morphological innovations, geography, ecology,
      development, species interactions and diversifications, and geology are needed
      and should shed insights into the patterns of evolutionary assembly and
      radiations in this fascinating region. 

PMID- 24575122
TI  - A glance at quality score: implication for de novo transcriptome reconstruction
      of Illumina reads.
AB  - Downstream analyses of short-reads from next-generation sequencing platforms are
      often preceded by a pre-processing step that removes uncalled and wrongly called
      bases. Standard approaches rely on their associated base quality scores to retain
      the read or a portion of it when the score is above a predefined threshold. It is
      difficult to differentiate sequencing error from biological variation without a
      reference using quality scores. The effects of quality score based trimming have
      not been systematically studied in de novo transcriptome assembly. Using RNA-Seq
      data produced from Illumina, we teased out the effects of quality score based
      filtering or trimming on de novo transcriptome reconstruction. We showed that
      assemblies produced from reads subjected to different quality score thresholds
      contain truncated and missing transfrags when compared to those from untrimmed
      reads. Our data supports the fact that de novo assembling of untrimmed data is
      challenging for de Bruijn graph assemblers. However, our results indicates that
      comparing the assemblies from untrimmed and trimmed read subsets can suggest
      appropriate filtering parameters and enable selection of the optimum de novo
      transcriptome assembly in non-model organisms. 

PMID- 24575121
TI  - The struggle to find reliable results in exome sequencing data: filtering out
      Mendelian errors.
AB  - Next Generation Sequencing studies generate a large quantity of genetic data in a
      relatively cost and time efficient manner and provide an unprecedented
      opportunity to identify candidate causative variants that lead to disease
      phenotypes. A challenge to these studies is the generation of sequencing
      artifacts by current technologies. To identify and characterize the properties
      that distinguish false positive variants from true variants, we sequenced a child
      and both parents (one trio) using DNA isolated from three sources (blood, buccal
      cells, and saliva). The trio strategy allowed us to identify variants in the
      proband that could not have been inherited from the parents (Mendelian errors)
      and would most likely indicate sequencing artifacts. Quality control measurements
      were examined and three measurements were found to identify the greatest number
      of Mendelian errors. These included read depth, genotype quality score, and
      alternate allele ratio. Filtering the variants on these measurements removed ~95%
      of the Mendelian errors while retaining 80% of the called variants. These filters
      were applied independently. After filtering, the concordance between identical
      samples isolated from different sources was 99.99% as compared to 87% before
      filtering. This high concordance suggests that different sources of DNA can be
      used in trio studies without affecting the ability to identify causative
      polymorphisms. To facilitate analysis of next generation sequencing data, we
      developed the Cincinnati Analytical Suite for Sequencing Informatics (CASSI) to
      store sequencing files, metadata (eg. relatedness information), file versioning,
      data filtering, variant annotation, and identify candidate causative
      polymorphisms that follow either de novo, rare recessive homozygous or compound
      heterozygous inheritance models. We conclude the data cleaning process improves
      the signal to noise ratio in terms of variants and facilitates the identification
      of candidate disease causative polymorphisms. 

PMID- 24575123
TI  - Associations of adiponectin with individual European ancestry in African
      Americans: the Jackson Heart Study.
AB  - BACKGROUND: Compared with European Americans, African Americans (AAs) exhibit
      lower levels of the cardio-metabolically protective adiponectin even after
      accounting for adiposity measures. Because few studies have examined in AA the
      association between adiponectin and genetic admixture, a dense panel of ancestry
      informative markers (AIMs) was used to estimate the individual proportions of
      European ancestry (PEA) for the AAs enrolled in a large community-based cohort,
      the Jackson Heart Study (JHS). We tested the hypothesis that plasma adiponectin
      and PEA are directly associated and assessed the interaction with a series of
      cardio-metabolic risk factors. METHODS: Plasma specimens from 1439 JHS
      participants were analyzed by ELISA for adiponectin levels. Using pseudo
      ancestral population genotype data from the HapMap Consortium, PEA was estimated
      with a panel of up to 1447 genome-wide preselected AIMs by a maximum likelihood
      approach. Interaction assessment, stepwise linear and cubic multivariable
      adjusted regression models were used to analyze the cross-sectional association
      between adiponectin and PEA. RESULTS: Among the study participants (62% women;
      mean age 48 +/- 12 years), the median (interquartile range) of PEA was 15.8
      (9.3)%. Body mass index (BMI) (p = 0.04) and insulin resistance (p = 0.0001)
      modified the association between adiponectin and PEA. Adiponectin was directly
      and linearly associated with PEA (beta = 0.62 +/- 0.28, p = 0.03) among non-obese
      (n = 673) and insulin sensitive participants (n = 1141; beta = 0.74 +/- 0.23, p =
      0.001), but not among those obese or with insulin resistance. No threshold point
      effect was detected for non-obese participants. CONCLUSIONS: In a large AA
      population, the individual proportion of European ancestry was linearly and
      directly associated with plasma adiponectin among non-obese and non insulin
      resistant participants, pointing to the interaction of genetic and metabolic
      factors influencing adiponectin levels.

PMID- 24575125
TI  - The origin, function and diagnostic potential of extracellular microRNA in human
      body fluids.

PMID- 24575124
TI  - Alternative splicing during Arabidopsis flower development results in
      constitutive and stage-regulated isoforms.
AB  - Alternative splicing (AS) is a process in eukaryotic gene expression, in which
      the primary transcript of a multi-exon gene is spliced into two or more different
      mature transcripts, thereby increasing proteome diversity. AS is often regulated
      differentially between different tissues or developmental stages. Recent studies
      suggested that up to 60% of intron-containing genes in Arabidopsis thaliana
      undergo AS. Yet little is known about this complicated and important process
      during floral development. To investigate the preferential expression of
      different isoforms of individual alternatively spliced genes, we used high
      throughput RNA-Seq technology to explore the transcriptomes of three floral
      development stages of Arabidopsis thaliana and obtained information of various AS
      events. We identified approximately 24,000 genes that were expressed at one or
      more of these stages, and found that nearly 25% of multi-exon genes had two or
      more spliced variants. This is less frequent than the previously reported 40-60%
      for multiple organs and stages of A. thaliana, indicating that many genes
      expressed in floral development function with a single predominant isoform. On
      the other hand, 1716 isoforms were differentially expressed between the three
      stages, suggesting that AS might still play important roles in stage transition
      during floral development. Moreover, 337 novel transcribed regions were
      identified and most of them have a single exon. Taken together, our analyses
      provide a comprehensive survey of AS in floral development and facilitate further
      genomic and genetic studies. 

PMID- 24575127
TI  - Lock-out valve to decrease catheter-associated urinary tract infections.
AB  - Patients with long-term indwelling urinary catheters are at an increased risk for
      urinary tract infection due to bacteriuria. Catheter-associated urinary tract
      infections (CAUTIs) are a significant source of morbidity and mortality in long
      term care facilities as well as in ambulatory patients requiring long-term
      catheterization. There is increased interest in the financial impact of CAUTI as
      Medicare no longer provides reimbursement for nosocomial CAUTIs. Ascending
      bacteria may in part enter the closed drainage system when the patient switches
      between leg and night collection bags. In an attempt to reduce this ascent, a
      double valve lock-out system was devised that maintains a closed system during
      bag exchange. The concept is introduced and CAUTIs are reviewed. 

PMID- 24575128
TI  - Diethylstilbestrol 1 mg in the Treatment of Acute Urinary Retention due to
      Prostatic Obstruction in the Elderly: A Preliminary Study.
AB  - Patients who failed a catheter-free trial after acute urinary retention and one
      week of full dose alpha-blocker and 5-alpha-reductase inhibitor were offered
      Diethylstilbestrol 1 mg plus Aspirin 100 mg over 4 weeks. Prostate volume, age,
      serum creatinine, and initial retention drained urine volume were recorded. After
      excluding cardiovascular morbidity (n = 7), upper urinary tract dilation (n = 3),
      compromised renal function (n = 2), urinary tract infection (n = 2), neurological
      diagnosis (n = 2), or preferred immediate channel transurethral resection of
      prostate (n = 5), 48 of 69 consecutive patients >=70 years were included. Mean
      age was 76.6 years (70-84), mean prostate volume 90 cm(3) (42-128), and mean
      follow-up 204 days; 58% (28/48) were passing urine and 42% (20/48) were catheter
      dependent after 4 weeks Diethylstilbestrol trial. Mean age and drained urine
      volume of catheter dependent patients were 82.4 years and 850 mL compared with
      74.6 years and 530 mL in catheter-free men, respectively. Age and drained urine
      volume were independent predictors of catheter-free trial (both P < 0.01).
      Seventy-five percent (6/8) of patients 80 years and older were catheter
      dependent. Transient nipple/breast tenderness and gynecomastia were the only
      adverse effects reported by 21% (10/48) and 4% (2/48), respectively. No patient
      presented severe complications. 

PMID- 24575130
TI  - Endocannabinoids and reproduction.

PMID- 24575129
TI  - Evaluation of serum 25-hydroxyvitamin d as a predictor of carotid intima-media
      thickness and carotid total plaque area in nonsmokers: the tromso study.
AB  - Objective. Altered calcium homeostasis has been linked to increased intima-media
      thickness (IMT) and plaques. We aimed to investigate whether serum 25
      hydroxyvitamin D (25(OH)D) and serum calcium are associated with IMT and plaques
      in nonsmoking population. Methods. Ultrasound of the right carotid artery with
      the measurements of IMT and plaques was performed in 4194 nonsmoking subjects
      with available measurements of serum 25(OH)D and total calcium. Linear regression
      was applied to study the linear relationships between variables. Multinomial
      logistic regression was used to evaluate predictors of increased IMT and total
      plaque area (TPA), adjusted for age, body mass index, systolic blood pressure,
      and total cholesterol. Results. There was no significant linear relationship
      between mean IMT, TPA, and either serum 25(OH)D or total serum calcium. One SD
      increase in serum 25(OH)D was independently associated with increased odds of
      being in the highest quartile of IMT in men (OR 1.30, 95% CI 1.12, 1.51). In
      women, 1 SD increase in serum 25(OH)D was independently associated with increased
      risk of being in the upper tertile of TPA (OR 1.15, 95% CI 1.01, 1.33).
      Conclusions. Impaired calcium homeostasis has no consistent association with mean
      IMT and TPA; however, increased serum 25(OH)D may predict subclinical
      atherosclerosis in nonsmokers. 

PMID- 24575126
TI  - Computer aided diagnostic support system for skin cancer: a review of techniques
      and algorithms.
AB  - Image-based computer aided diagnosis systems have significant potential for
      screening and early detection of malignant melanoma. We review the state of the
      art in these systems and examine current practices, problems, and prospects of
      image acquisition, pre-processing, segmentation, feature extraction and
      selection, and classification of dermoscopic images. This paper reports
      statistics and results from the most important implementations reported to date.
      We compared the performance of several classifiers specifically developed for
      skin lesion diagnosis and discussed the corresponding findings. Whenever
      available, indication of various conditions that affect the technique's
      performance is reported. We suggest a framework for comparative assessment of
      skin cancer diagnostic models and review the results based on these models. The
      deficiencies in some of the existing studies are highlighted and suggestions for
      future research are provided. 

PMID- 24575132
TI  - Effect of conjugated linoleic acid and omega-3 fatty acid supplementation on
      inflammatory and oxidative stress markers in atherosclerotic patients.
AB  - BACKGROUND: Cardiovascular disease is the major cause of morbidity, mortality,
      and disability in Iranian people. Inflammation and oxidative processes are key
      components of cardiovascular disease. The aim of this study was to evaluate the
      effect of conjugated linoleic acids (CLA) and omega-3 fatty acid (omega-3 fatty
      acids) supplementation on inflammation markers and oxidative stress in
      atherosclerotic patients. METHODS: This study was a two-month clinical,
      randomized trial. 90 volunteers who referred to Emam Reza Heart Clinic of Shiraz
      University of Medical Sciences (Shiraz, Iran) from February to March 2011 and had
      the inclusion criteria of this study were selected. Participants were classified
      into 3 groups receiving 3 g/d CLA, 1920 mg/d omega-3, or placebo for 2 months. C
      reactive protein (CRP), interleukin-6 (IL-6), malondialdehyde (MDA), and
      glutathione peroxidase (GPx) were measured before and after supplementation.
      RESULTS: The hs-CRP level decreased significantly in both the omega-3 and CLA
      group (P < 0.05). IL-6 reduced significantly in the omega-3 group, but the
      reduction of IL-6 levels in the CLA group was not significant. GPx increased in
      the CLA and omega-3 groups (P < 0.05). MDA level decreased significantly in both
      omega-3 and CLA groups (P < 0.05). Comparison between the groups indicates a
      significant change in CRP levels in the omega-3 group relative to the control
      group. However, other indices did not cause any significant change in the omega-3
      and CLA groups in comparison to the control group. CONCLUSION: Diet
      supplementation with CLA and omega-3 can have a beneficial effect on some indices
      of inflammatory and oxidative stress.

PMID- 24575131
TI  - Soluble form of receptor for advanced glycation end products is associated with
      obesity and metabolic syndrome in adolescents.
AB  - The aim of this cross-sectional study was to investigate the relationship between
      soluble form of receptor for advanced glycation end products (sRAGE), obesity,
      and metabolic syndrome (MetS) in adolescents. A total of 522 male and 561 female
      adolescents were enrolled into the final analyses. Anthropometric parameters,
      blood pressure, blood biochemistry, fasting insulin, and plasma sRAGE levels were
      measured. In males, sRAGE was significantly and inversely correlated with waist
      circumference (WC), body mass index (BMI), systolic blood pressure, triglyceride
      (TG), low density lipoprotein cholesterol (LDL-C), and homeostasis model
      assessment-insulin resistance (HOMA-IR). Only WC and BMI were significantly and
      inversely correlated with sRAGE in females. Using linear regression analysis
      adjusting for age and gender, significant association was found between sRAGE and
      WC, BMI, TG, LDL-C, and HOMA-IR in adolescents of either gender (P < 0.05). This
      association was abolished when further adjusting BMI. In addition, sRAGE was
      significantly and inversely correlated with the increasing number of components
      of MetS in males (P for trend = 0.006) but not in females (P for trend = 0.422).
      In conclusion, plasma sRAGE is associated with obesity and MetS among
      adolescents. BMI may be the most important determinant of sRAGE levels in
      adolescents. 

PMID- 24575133
TI  - Relationship between dietary approaches to stop hypertension score and presence
      or absence of coronary heart diseases in patients referring to Imam Hossein
      Hospital, Tehran, Iran.
AB  - BACKGROUND: The dietary approaches to stop hypertension (DASH) dietary pattern
      reduces blood pressure. However, there is little information about the
      relationship between DASH and coronary heart diseases. This study aimed to assess
      the relationship between a DASH-style diet adherence score and coronary heart
      diseases (CHD) in patients referring for coronary angiography. METHODS: In this
      study, 201 adults (102 males, 99 females) within the age range of 40-80 years who
      referred for coronary angiography were selected. Diet was evaluated using a
      validated food frequency questionnaire. DASH score was calculated based on 8 food
      components (fruits, vegetables, whole grains, nuts and legumes, low fat dairy,
      red/processed meats, soft drinks/sweets, and sodium). The relationship between
      DASH score and CHD was assessed using logistic regression analysis. RESULTS: Mean
      of DASH score was 23.99 +/- 4.41. Individuals in the highest quartile of DASH
      score were less likely to have CHD [odds ratio (OR) = 0.38, 95% confidence
      interval (CI): 0.16-0.86]. However, after adjustment for gender or smoking, there
      was little evidence that coronary heart disease was associated with DASH diet
      score. There was a significant negative correlation between DASH score and
      diastolic blood pressure (P <= 0.05). CONCLUSION: In conclusion, having a diet
      similar to DASH plan was not independently related to CHD in this study. This
      might indicate that having a healthy dietary pattern, such as DASH pattern, is
      highly related to gender (dietary pattern is healthier in women than men) or
      smoking habit (non-smokers have healthier dietary pattern compared to smokers).

PMID- 24575134
TI  - Clinical investigation of the acute effects of pomegranate juice on blood
      pressure and endothelial function in hypertensive individuals.
AB  - BACKGROUND: Pomegranate juice (PJ) is rich in bioactive phytochemicals with
      antioxidant, and anti-inflammatory and cardioprotective functions. The present
      trial investigated the acute effects of PJ consumption on blood pressure and
      markers of endothelial function. METHODS: In this single-arm study, thirteen
      hypertensive men aged 39-68 years were recruited. Included subjects were assigned
      to natural PJ (150 ml/day) following a 12 hour fast. Systolic blood pressure
      (SBP), diastolic blood pressure (DBP), and flow-mediated dilation (FMD), along
      with serum concentrations of C-reactive protein (CRP), intracellular adhesion
      molecule-1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), E-selectin and
      interleukin-6 (IL-6) were measured at baseline and 4-6 hours after PJ
      consumption. RESULTS: Comparison of pre- vs. post-trial values revealed a
      significant reduction in both SBP (7%; P = 0.013) and DBP (6%; P < 0.010).
      However, changes in FMD (20%) as well as circulating levels of CRP, ICAM-1, VCAM
      1, E-selectin, and IL-6 did not reach statistical significance (P = 0.172).
      CONCLUSION: PJ has promising acute hypotensive properties. Consumption of PJ
      could be considered in the context of both dietary and pharmacological
      interventions for hypertension.

PMID- 24575135
TI  - Modulation of coronary artery disease risk factors by menopausal status: A
      population based study among Iranian women (KERCADRStudy).
AB  - BACKGROUND: Menopause is now viewed as a risk factor for coronary heart diseases
      (CHD). There is a scarcity of evidence concerning the effects of menopause on
      coronary artery disease (CAD) risk factors. The present study aimed to evaluate
      the effects of menopausal status on CAD risk factors. METHODS: The present study
      was designed as part of the Kerman coronary artery disease risk study (KERCADRS)
      that was a population-based study among a cohort of 6000 individuals aged 15 to
      75 years in Kerman, Iran. Only women aged 35 to 60 years were enrolled.
      Participants were categorized according to reproductive age into the three groups
      of premenopausal, perimenopausal, and postmenopausal states. RESULTS: The
      premenopausal status was accompanied with lower levels of triglyceride (TG),
      cholesterol, fasting plasma glucose (FPG), and blood pressure compared with the
      other two groups (P < 0.001). In addition, women in the postmenopausal group had
      higher levels of low-density lipoprotein (LDL) in comparison with the other two
      groups (P < 0.001). After adjusting for age, total cholesterol and LDL levels
      were significantly higher in the postmenopausal group compared with the other two
      groups (P < 0.05). In addition, total cholesterol and LDL levels, and systolic
      blood pressure were statistically different according to menopausal status after
      adjustment for both age and body mass index (P < 0.05). CONCLUSION: The increased
      risk of cardiovascular disease in postmenopausal period can be explained by
      elevated levels of lipid profile and increased systolic blood pressure,
      regardless of effects of advanced age or other anthropometric parameters.

PMID- 24575136
TI  - Impact of the components of Mediterranean nutrition regimen on long-term
      prognosis of diabetic patients with coronary artery disease.
AB  - BACKGROUND: The impact of different nutritional regimens on long-term prognosis
      and outcome in diabetic patients with coronary artery disease (CAD) has been
      questioned. Therefore, the objective of the present study was to determine the
      effects of different nutritional components of Mediterranean regimen on long-term
      cardiovascular events in diabetic patients with CAD in the Iranian population.
      METHODS: In a prospective cohort study, we recruited 233 consecutive patients
      with the diagnosis of type 2 diabetes mellitus and with at least 6 months of
      documented CAD. Nutritional assessment was obtained by a validated semi
      quantitative food frequency questionnaire (FFQ) and the diet score was calculated
      on the basis of the Mediterranean diet quality index (Med-DQI). For Assessing
      long-term CAD prognosis, the patients were followed by telephone for one year.
      The study endpoint was long-term major adverse cardiac and cerebrovascular event
      (MACCE). RESULTS: Death was observed in 19 patients (8.2%) during the one-year
      follow-up. Two patients (0.9%) suffered non-fatal myocardial infarction and 14
      (6.0%) needed revascularization within 1 year after discharge from hospital.
      Overall MACCE within one year in the study population was 12.4%. There were
      significant differences between number of deaths and dietary scores of saturated
      fatty acid, cholesterol, meats, fish, and fruit and vegetables (P < 0.05).
      Moreover, significant differences were found between MACCE rate and dietary
      scores of saturated fatty acid, cholesterol, and fruit and vegetables (P < 0.05).
      Using multivariate logistic regression models, Mediterranean dietary regimen
      could effectively predict long-term death as well as MACCE adjusted for gender
      and age variables. CONCLUSION: Mediterranean dietary regimens, including low
      level of cholesterol and saturated fatty acid, can effectively improve long-term
      outcome including death and MACCE in diabetic patients with CAD.

PMID- 24575137
TI  - Amiodarone versus lidocaine for the prevention of reperfusion ventricular
      fibrillation: A randomized clinical trial.
AB  - BACKGROUND: Reperfusion ventricular fibrillation after aortic cross clamp is one
      of the important complications of open cardiac surgery and its prevention could
      reduce myocardial injuries. This study aimed to evaluate the efficacy of single
      dose of amiodarone or lidocaine by the way of pump circuit three minutes before
      aortic cross clamp release and compare the results with normal saline as placebo
      in a randomized double blinded controlled trial. METHODS: One hundred fifty
      patients scheduled for first time elective coronary artery bypass graft surgery
      were randomly assigned to receive either single dose of amiodarone (150 mg),
      lidocaine (100 mg), or normal saline (5 ml) three minutes before aortic cross
      clamp release. The incidence of ventricular fibrillation and the need for reuse
      of drug were compared between these groups by chi-square, Student's t-test, Mann
      Whitney test, and One-way ANOVA. SPSS software was used for statistical analysis.
      RESULTS: The incidence of ventricular fibrillation is higher in the placebo group
      (15.9%) compare to lidocaine (11.8%) and amiodarone (8.9%) groups; however, there
      was no statistical difference among the three groups (P = 0.41). Moreover, the
      reuse of amiodarone (22.7%) was statistically higher (P < 0.05) than lidocaine
      (5.9%). CONCLUSION: This study showed no difference among lidocaine, amiodarone,
      and placebo in preventing ventricular fibrillation after aortic cross clamp
      release.

PMID- 24575138
TI  - Designing and standardizing a questionnaire for evaluating knowledge, attitude,
      and practice of Iranian adults with cardiovascular diseases about oral health.
AB  - BACKGROUND: Cardiovascular diseases are the most common cause of death in Iran.
      Moreover, periodontal diseases are very common in our country. In this study, we
      have designed a standardized questionnaire for evaluating knowledge, attitude,
      and practice (KAP) of Iranian adult patients with cardiovascular diseases about
      oral health. METHODS: For designing and standardizing a self-administered
      questionnaire, we performed a cross-sectional pilot study on 51 cases with
      periodontal complaints. A dentist carried out the physical examination to
      determine oral health indicators. Twelve experts and ten lay people of the target
      population answered questions about validity. Cronbach's alpha, factor analysis,
      and Pearson correlation coefficients were used in the analysis. RESULTS: The
      cases of this pilot study were middle aged, with moderate financial and health
      status, but low oral health and educational level. Debris score was correlated
      with all other physical exam findings except decay, missing, and filled (DMF).
      Reliability was 0.826 according to Cronbach's alpha score. Face validity was
      higher than 80%. Content validities of the whole of the questionnaire were 85.98%
      for clarity, 78.05% for relevancy, 85.16% for simplicity, and 82.32% for
      consistency of each question with the question set. Factor analysis showed that
      15 components explain 74% of the total variance. CONCLUSION: This questionnaire
      is culturally adjusted and appropriate for our community, valid and reliable, and
      sufficiently estimates the variance of the oral health status. It can be used as
      a standard tool in further studies in adult population of the Iranian middle aged
      patients with low level of education and moderate socioeconomic status.

PMID- 24575139
TI  - Impacts of fresh lime juice and peel on atherosclerosis progression in an animal
      model.
AB  - BACKGROUND: The main protective role of antioxidants in the progression of
      atherosclerosis has been shown in some studies. Therefore, this project evaluated
      the effects of Citrus aurantifolia (Christm) juice and peel on antioxidant
      activity and atherosclerosis progression in rabbits receiving a
      hypercholesterolemic diet. METHODS: Forty white New Zealand male rabbits were
      randomly allocated to four groups. All groups were on hypercholesterolemic diet
      for two months. While the first group was considered as the hypercholesterolemic
      control, groups 2 and 3 (intervention groups) received 5 ml/day lime juice and 1
      g/day dried lime peel powder, respectively. Group 4 was fed a normal diet (normal
      control). Before and after the study, weight was measured and a fasting blood
      specimen was taken from the rabbits. Serum lipids analyses and antioxidant
      activity evaluations were then performed. The rabbits' aorta and coronary
      arteries were separated and the presence of fatty streaks was studied. RESULTS:
      Comparing to the hypercholesterolemic control group (-25.2 +/- 7.0), only the
      plasma total antioxidant capacity change was significantly more in rabbits
      supplemented with lime juice (16.3 +/- 14.7) and peel (8.6 +/- 7.1) (P = 0.008).
      The presence of fatty streaks in coronary arteries and aorta of the intervention
      groups [juice (0.2 +/- 0.01); peel (0.0 +/- 0.00)] was significantly decreased
      compared to the hypercholesterolemic control group (1.2 +/- 0.4) (P < 0.001).
      CONCLUSION: Based on our findings, Citrus aurantifolia peel and juice increase
      plasma antioxidant capacity in rabbits, and can thus prevent or decelerate the
      process of atherogenesis. However, lime peel is more effective than lime juice.

PMID- 24575140
TI  - Comparison of effects of soft margarine, blended, ghee, and unhydrogenated oil
      with hydrogenated oil on serum lipids: A randomized clinical trail.
AB  - BACKGROUND: Trans fatty acids (TFAs) are known as the most harmful type of
      dietary fats. Therefore, this study was done to compare the effects of some
      different oils including unhydrogenated, blended, ghee, and soft magazine with
      hydrogenated oil on serum lipid profile of healthy adults. METHODS: This study
      was a randomized clinical trial conducted on 206 healthy participants of 20 to 60
      years of age. Subjects were randomly divided into 5 groups and each of them was
      treated with a diet containing unhydrogenated oil, ghee, blended oil, soft
      margarine, or hydrogenated oil for 40 days. Fasting serum lipids were measured
      before and after the study. RESULTS: Compared to hydrogenated oil, total
      cholesterol (TC) and triglyceride (TG) had a significant reduction in all groups,
      LDL-C declined in unhydrogenated oil and soft margarine groups, and
      apolipoprotein (Apo) B only in unhydrogenated oil group (all P < 0.05). However,
      there was a significant enhancement in ApoA of ghee oil (P < 0.001). CONCLUSION:
      Consuming unhydrogenated oil, ghee, soft margarine, and blended oil had some
      beneficial effects on serum lipids.

PMID- 24575141
TI  - Pivotal role of microRNA-33 in metabolic syndrome: A systematic review.
AB  - Metabolic syndrome (MetS) is a major public health concerns and increase in the
      incidence of MetS caused a rise in the rates of global morbidity, and mortality
      due to cardiovascular disease and diabetes. Lifestyle modification, a healthy
      diet, and pharmacological treatment and bariatric surgery are recommended in
      order to control this syndrome. Molecular mechanisms of metabolic disorders are
      essential in order to develop novel, valid therapeutic strategies. MicroRNA-33
      plays imperative regulatory roles in a variety of biological processes including
      collaboration with sterol regulatory element-binding protein (SREBP) to maintain
      cholesterol homeostasis, high-density lipoprotein formation, fatty acid
      oxidation, and insulin signaling. Investigation of these molecules and their
      genetic targets may potentially identify new pathways involved in complex
      metabolic disease processes, improve our understanding of metabolic disorders,
      and influence future approaches to the treatment of obesity. This article reviews
      the role of miRNA-33 in metabolic syndrome, and highlights the potential of using
      miRNA-33 as a novel biomarker and therapeutic target for this syndrome. 

PMID- 24575142
TI  - Selection of best door-to-cardiac regeneration (D2CR) time.
AB  - In spite of great progress in the treatment of acute coronary syndrome (ACS)
      events in reperfusion era, patients are still at risk for development of heart
      failure due to negative remodeling. Thus, the importance of regenerative
      therapies in parallel with reperfusion strategies is fundamental. A key feature
      in this case is obtaining the most appropriate door-to-cardiac regeneration
      (D2CR) time. This golden time in which fresh stem cells can invade scare-prone
      tissue could be defined as door-to-cardiac stem cell (D2CSC) plus door-to-cardiac
      regeneration (D2CR) time. Application of stem cells in this golden time allows
      comprehensive regeneration and reconstruction. Therefore, the aim of this study
      was to plan the outlines of simultaneous application of cellular and vascular
      reconstruction strategies. 

PMID- 24575144
TI  - Effect of Wasabi Component 6-(Methylsulfinyl)hexyl Isothiocyanate and Derivatives
      on Human Pancreatic Cancer Cells.
AB  - The naturally occurring compound 6-(methylsulfinyl)hexyl isothiocyanate (6-MITC)
      was isolated from Wasabia japonica (Wasabi), a pungent spice used in Japanese
      food worldwide. The synthetic derivatives 6-(methylsulfenyl)hexyl isothiocyanate
      (I7447) and 6-(methylsulfonyl)hexyl isothiocyanate (I7557) are small molecule
      compounds derived from 6-MITC. This study aimed to evaluate the effect of these
      compounds on human pancreatic cancer cells. Human pancreatic cancer cell lines
      PANC-1 and BxPC-3 were used to perform an MTT assay for cell viability and Liu's
      stain for morphological observation. The cell cycle was analyzed by DNA
      histogram. Aldehyde dehydrogenase (ALDH) activity was used as a marker for cancer
      stem cells (CSC). Western blotting was performed for the expression of proteins
      related to CSC signaling. The results showed that compounds 6-MITC and I7557, but
      not I7447, inhibited viability of both PANC-1 and BxPC-3 cells. Morphological
      observation showed mitotic arrest and apoptosis in 6-MITC- and I7557-treated
      cells. These two compounds induced G2/M phase arrest and hypoploid population.
      Percentages of ALDH-positive PANC-1 cells were markedly reduced by 6-MITC and
      I7557 treatment. The expression of CSC signaling molecule SOX2, but not NOTCH1,
      ABCG2, Sonic hedgehog, or OCT4, was inhibited by 6-MITC and I7557. In conclusion,
      wasabi compounds 6-MITC and I7557 may possess activity against the growth and CSC
      phenotypes of human pancreatic cancer cells. 

PMID- 24575146
TI  - Clear cell variant of solid pseudopapillary neoplasm of pancreas diagnosed by
      fine needle aspiration: A case report and review of the literature.
AB  - Solid pseudopapillary neoplasm (SPN) of the pancreas is a rare tumor of uncertain
      malignant potential, predominantly affecting young adult females. We report a
      case of clear cell variant of SPN, which was diagnosed by fine needle aspiration
      biopsy. The aspirate was highly cellular and exhibited delicate branching
      papillary structures with central capillaries covered with several layers of
      plasmacytoid tumor cells. Acinar and rosette-like formations, as well as single
      neoplastic cells were also observed. An unusual cytologic feature was the
      presence of large, clear cytoplasmic vacuoles. The diagnosis of SPN was confirmed
      by characteristic immunocytochemical staining pattern including nuclear staining
      for beta-catenin, cytoplasmic staining for vimentin and lack of reactivity for
      cytokeratin. 

PMID- 24575147
TI  - Who has the authority to change a theory? Everyone! A commentary on Head and
      Noar.

PMID- 24575143
TI  - Cell-mediated immune responses in paraneoplastic neurological syndromes.
AB  - Paraneoplastic neurological syndromes (PNS) are disorders of the nervous system
      that are associated with remote effects of malignancy. PNS are considered to have
      an autoimmune pathology. It has been suggested that immune antitumor responses
      are the origin of improved outcome in PNS. We describe cell-mediated immune
      responses in PNS and their potential contributions to antitumor reactions.
      Experimental and neuropathological studies have revealed infiltrates in nervous
      tissue and disturbances in lymphocyte populations in both cerebrospinal fluid and
      peripheral blood. A predominance of cytotoxic T lymphocytes (CTLs) over T helper
      cells has been observed. CTLs can be specifically aggressive against antigens
      shared by tumors and nervous tissue. Based on genetic studies, a common clonal
      origin of lymphocytes from blood, tumor, and nervous tissue is suggested.
      Suppressive regulatory T (Treg) lymphocytes are dysfunctional. Simultaneously, in
      tumor tissue, more intense cell-mediated immune responses are observed, which
      often coincide with a less aggressive course of neoplastic disease. An increased
      titer of onconeural antibodies is also related to better prognoses in patients
      without PNS. The evaluation of onconeural and neuronal surface antibodies was
      recommended in current guidelines. The link between PNS emergence and antitumor
      responses may result from more active CTLs and less functional Treg lymphocytes. 

PMID- 24575145
TI  - Evaluation of a triple combination of cytokeratin 20, p53 and CD44 for improving
      detection of urothelial carcinoma in urine cytology specimens.
AB  - BACKGROUND: Atypical urine cytology results trigger cystoscopy or molecular
      tests, both of which are costly, complex and difficult to perform tests. Several
      immunostains are being investigated to improve cancer detection; however,
      cytology material is limited and restricts the use of multiple immunostains. This
      study was designed to determine the utility of a cocktail of three stains,
      cytokeratin (CK20), p53 and CD44 in urine cytology samples for improving the
      detection of urothelial carcinoma. MATERIALS AND METHODS: Urine cytology
      specimens with cell blocks containing adequate cytologic material between 2005
      and 2010 and subsequent follow-up biopsy and/or Urovysion test (102 cases
      including 29 negative, 56 atypical and 17 malignant) were included in the study
      and evaluated with the triple stain. Results were first validated on the positive
      and negative cases and then applied to the atypical cases to determine the
      utility in the diagnosis of urothelial carcinoma. RESULTS: Based on the
      validation and published literature, two distinct immunoprofiles were defined -
      malignant, characterized by at least five CK20 and/or p53 positive atypical cells
      and reactive, all other staining patterns. The malignant immunoprofile showed 88%
      sensitivity, 78% specificity, 74% positive predictive value (PPV) and 90%
      negative predictive value (NPV) for detecting urothelial carcinoma. These values
      improved to 95% sensitivity and 96% NPV when low-grade urothelial carcinoma cases
      were excluded. SUMMARY: Our results indicate that the triple stain is an
      inexpensive, easy to perform test most useful for differentiating high-grade
      urothelial carcinoma from its mimics. However Inclusion of CD44 in the cocktail
      did not provide additional value and is best excluded.

PMID- 24575149
TI  - High-performance electronics for time-of-flight PET systems.
AB  - We have designed and built a high-performance readout electronics system for time
      of-flight positron emission tomography (TOF PET) cameras. The electronics
      architecture is based on the electronics for a commercial whole-body PET camera
      (Siemens/CPS Cardinal electronics), modified to improve the timing performance.
      The fundamental contributions in the electronics that can limit the timing
      resolution include the constant fraction discriminator (CFD), which converts the
      analog electrical signal from the photo-detector to a digital signal whose
      leading edge is time-correlated with the input signal, and the time-to-digital
      converter (TDC), which provides a time stamp for the CFD output. Coincident
      events are identified by digitally comparing the values of the time stamps. In
      the Cardinal electronics, the front-end processing electronics are performed by
      an Analog subsection board, which has two application-specific integrated
      circuits (ASICs), each servicing a PET block detector module. The ASIC has a
      built-in CFD and TDC. We found that a significant degradation in the timing
      resolution comes from the ASIC's CFD and TDC. Therefore, we have designed and
      built an improved Analog subsection board that replaces the ASIC's CFD and TDC
      with a high-performance CFD (made with discrete components) and TDC (using the
      CERN high-performance TDC ASIC). The improved Analog subsection board is used in
      a custom single-ring LSO-based TOF PET camera. The electronics system achieves a
      timing resolution of 60 ps FWHM. Prototype TOF detector modules are read out with
      the electronics system and give coincidence timing resolutions of 259 ps FWHM and
      156 ps FWHM for detector modules coupled to LSO and LaBr3 crystals respectively.

PMID- 24575150
TI  - A machine learning approach for specification of spinal cord injuries using
      fractional anisotropy values obtained from diffusion tensor images.
AB  - Diffusion Tensor Imaging (DTI) uses in vivo images that describe extracellular
      structures by measuring the diffusion of water molecules. These images capture
      axonal movement and orientation using echo-planar imaging and provide critical
      information for evaluating lesions and structural damage in the central nervous
      system. This information can be used for prediction of Spinal Cord Injuries
      (SCIs) and for assessment of patients who are recovering from such injuries. In
      this paper, we propose a classification scheme for identifying healthy
      individuals and patients. In the proposed scheme, a dataset is first constructed
      from DTI images, after which the constructed dataset undergoes feature selection
      and classification. The experiment results show that the proposed scheme aids in
      the diagnosis of SCIs. 

PMID- 24575148
TI  - Helix versus coil polypeptide macromers: gel networks with decoupled stiffness
      and permeability.
AB  - As a platform for investigating the individual effects of substrate stiffness,
      permeability, and ligand density on cellular behavior, we developed a set of
      hydrogels with stiffness tuned by polymer backbone rigidity, independent of cross
      link density and concentration. Previous studies report that poly(propargyl-L
      glutamate) (PPLG), synthesized by ring-opening polymerization of the N-carboxy
      anhydride of gamma-propargyl-L-glutamate (gammapLglu), adopts a rigid a-helix
      conformation: we hypothesized that a random copolymer (PPDLG) with equal amounts
      of gammapLglu and gamma-propargyl-D-glutamate (gammapDglu) monomers would exhibit
      a more flexible random coil conformation. The resulting macromers exhibited
      narrow molecular weight distributions (PDI = 1.15) and were grafted with ethylene
      glycol groups using a highly efficient "click" azide/alkyne cycloaddition
      reaction with average grafting efficiency of 97% for PPLG and 85% for PPDLG. The
      polypeptide secondary structure, characterized via circular dichroism
      spectroscopy, FTIR spectroscopy, and dynamic light scattering, is indeed
      dependent upon monomer chirality: PPLG exhibits an alpha-helix conformation while
      PPDLG adopts a random coil conformation. Hydrogel networks produced by cross
      linking either helical or random coil polypeptides with poly(ethylene glycol)
      (PEG) were analyzed for amount of swelling, gelation efficiency, and permeability
      to a model protein. In addition, the elastic modulus of helical and coil
      polypeptide gels was determined by AFM indentation in fluid. Importantly, we
      found that helical and coil polypeptide gels exhibited similar swelling and
      permeability but different stiffnesses, which correspond to predictions from the
      theory of semi-flexible chains.

PMID- 24575152
TI  - Conflicts of interest in medical school: missing policies and high need for
      student information at most German universities.
AB  - OBJECTIVES: Medical students interact with pharmaceutical representatives already
      during medical school. The goal of this study was to find out: Do policies exist
      at German medical faculties that govern the interactions between medical students
      and pharmaceutical representatives, do schools offer courses on the subject and
      do students attend these courses? And What are the attitudes of medical students
      concerning the role of pharmaceutical companies in medical teaching? METHODS: All
      36 German medical faculty deans and 1151 medical students at eight German
      universities were asked to complete a questionnaire of 4 and 7 questions,
      respectively, regarding the above mentioned topics. RESULTS: 30 (83.3%) deans and
      1038 (90.3%) medical students filled in the questionnaire, respectively.
      According to the deans' answers, only one school had a policy concerning
      conflicts of interest and one had a policy governing the interactions between
      medical students and industry. 8 (26.7%) deans showed an interest in constructing
      a policy or educational an activity on this subject. 149 (14.4%) students had
      participated in an activity that focussed the subject of conflicts of interest
      and 779 (77.8%) wanted more education on the subject. 701 (73.4%) were opposed to
      an improvement of medical studies through financial support by pharmaceutical
      companies, whereas 216 (21.9%) were of the opinion that students should not meet
      with pharmaceutical representatives. CONCLUSIONS: Unlike in other countries, like
      the US, most German medical faculties do not have policies that govern the
      interactions between medical students and pharmaceutical companies. Since most
      students want to be taught more about these interactions, the implementation of
      respective policies and lectures would be desirable.

PMID- 24575153
TI  - Motives of former interns in general practice for speciality-choice--results of a
      cross-sectional study among graduates 2007 to 2012.
AB  - BACKGROUND: The influence of a final-year elective internship in general practice
      (IGP) on motives affecting graduates' choice of specialty is the object of great
      public interest, yet still insufficiently evaluated. Longitudinal studies show
      the influence of numerous motives (e.g., work-life balance), but not following
      the IGP experience itself. Thus, we performed a cross-sectional questionnaire
      study of all graduates who completed the IGP in Saxony-Anhalt during 2007-2012
      regarding their motives for choosing a speciality. METHOD: A standardized
      questionnaire was sent to 109 former interns in general practice. The
      questionnaire contained 29 items addressing three topics (personal attitudes,
      concept of personal and professional life, motives for speciality choice) and
      used single-choice and multiple-choice answers, as well as Likert scales.
      Correlation analysis was carried out by means of Kendall's tau. RESULTS: The
      questionnaire reached 97 former interns, of which 45 (46%) responded. In the
      overall ranking of motives for speciality choice, family (71%), leisure time
      (66%) and job opportunities (48%) rated as more important than income (36%),
      mentoring (20%), status or scientific work (20%). Only 29% of the respondents
      stated that their speciality choice was changed by the IGP. If the speciality
      choice was already established before the IGP, the influence of the IGP on
      speciality choice was significantly low (r = -.5; p < .01). However, if the IGP
      had an influence on speciality choice, it was correlated with a new perception of
      general practice (r = .36; p<.01). This new perception was associated with a
      positive influence of the medical teacher during the IGP. CONCLUSION: The final
      year IGP is an opportunity to change the perception of general practice in
      students who are still undecided. This can lead to different speciality choices
      in a subgroup. Personal attitudes and concepts of personal life and career were
      also important factors affecting speciality choice. The aspects of the positive
      influence exerted by medical teachers on those students who are still undecided
      during the IGP should be carefully evaluated.

PMID- 24575156
TI  - OnlineTED.com--a novel web-based audience response system for higher education. A
      pilot study to evaluate user acceptance.
AB  - BACKGROUND AND AIM: Audience response (AR) systems are increasingly used in
      undergraduate medical education. However, high costs and complexity of
      conventional AR systems often limit their use. Here we present a novel AR system
      that is platform independent and does not require hardware clickers or additional
      software to be installed. METHODS AND RESULTS: "OnlineTED" was developed at
      Technische Universitat Munchen (TUM) based on Hypertext Preprocessor (PHP) with a
      My Structured Query Language (MySQL)-database as server- and Javascript as client
      side programming languages. "OnlineTED" enables lecturers to create and manage
      question sets online and start polls in-class via a web-browser. Students can
      participate in the polls with any internet-enabled device (smartphones, tablet
      PCs or laptops). A paper-based survey was conducted with undergraduate medical
      students and lecturers at TUM to compare "OnlineTED" with conventional AR systems
      using clickers. "OnlineTED" received above-average evaluation results by both
      students and lecturers at TUM and was seen on par or superior to conventional AR
      systems. The survey results indicated that up to 80% of students at TUM own an
      internet-enabled device (smartphone or tablet-PC) for participation in web-based
      AR technologies. SUMMARY AND CONCLUSION: "OnlineTED" is a novel web-based and
      platform-independent AR system for higher education that was well received by
      students and lecturers. As a non-commercial alternative to conventional AR
      systems it may foster interactive teaching in undergraduate education, in
      particular with large audiences.

PMID- 24575157
TI  - Teaching first-year medical students in basic clinical and procedural skills--a
      novel course concept at a medical school in Austria.
AB  - INTRODUCTION: Clerkships are still the main source for undergraduate medical
      students to acquire necessary skills. However, these educational experiences may
      not be sufficient, as there are significant deficiencies in the clinical
      experience and practical expertise of medical students. PROJECT DESCRIPTION: An
      innovative course teaching basic clinical and procedural skills to first-year
      medical students has been implemented at the Medical University of Graz, aiming
      at preparing students for clerkships and clinical electives. The course is based
      on several didactic elements: standardized and clinically relevant contents, dual
      (theoretical and virtual) pre-course preparation, student peer-teaching, small
      teaching groups, hands-on training, and the use of medical simulation. This is
      the first course of its kind at a medical school in Austria, and its conceptual
      design as well as the implementation process into the curriculum shall be
      described. EVALUATION: Between November 2011 and January 2013, 418 students have
      successfully completed the course. Four online surveys among participating
      students have been performed, with 132 returned questionnaires. Students'
      satisfaction with all four practical course parts was high, as well as the
      assessment of clinical relevance of contents. Most students (88.6%) strongly
      agreed/agreed that they had learned a lot throughout the course. Two thirds of
      the students were motivated by the course to train the acquired skills regularly
      at our skills laboratory. Narrative feedbacks revealed elements contributing most
      to course success. CONCLUSIONS: First-year medical students highly appreciate
      practical skills training. Hands-on practice, peer-teaching, clinically relevant
      contents, and the use of medical simulation are valued most.

PMID- 24575158
TI  - Homeopathy as elective in undergraduate medical education--an opportunity for
      teaching professional core skills.
AB  - AIM: The evaluation of medical students' perceptions regarding an elective study
      course in Homeopathy in which small groups have participated annually for six
      years, at the Institute for General Practice and Family Medicine at the Otto Von
      Guericke University, Magdeburg. The course was assessed in terms of concept,
      delivery, and influence on students' professional development. METHODOLOGY: Since
      the autumn term of 2008/09, three group discussions have been conducted with
      thirty of the course participants (3 total electives). These discussions were
      semi-structured and guided by central topics; the analysis was qualitative and
      guided by content. RESULTS: The overall concept and implementation of the course
      were very successful. The main learning themes, that is, an emphasis on a more
      holistic and individual view of patients and the importance of a cooperative
      partnership between doctor and patient, were positively rated, regardless of the
      students' attitudes towards homeopathy. Their assessment was based on their
      previous experience and a comparison with conventional medical education.
      CONCLUSION: Homeopathy as an elective subject is not only useful for acquiring
      specific knowledge in integrative medicine, but also important as a means of
      developing physicians' core skills that are often not well considered in
      conventional medical education.

PMID- 24575159
TI  - DEGAM criteria catalogue for training practices in primary care--a proposal for
      the assessment of the structural quality of training practices.
AB  - BACKGROUND: Whilst the structure of primary care vocational training in Germany
      is being increasingly formalized there remains an abundance of disparate locally
      defined criteria for the training practices. Advanced medical training in the
      ambulatory setting has also been identified as an area of need by other
      specialties. GOAL: In contrast to the current practice of a unregulated
      authorization by regional medical associations this catalogue provide
      transparent, clearly defined criteria for the assignment of training practice
      status. METHODS: The first draft of the criteria catalogue integrates feedback
      from 30 academic general practitioners. The feasibility of the catalogue was
      tested by a further 30 surgeries. Analysis included an assessment of the
      sociodemographic characteristics of the trainers and their practices as well as
      satisfaction of the participants with the approved authorization period. RESULTS:
      The criteria catalogue comprises 19 items within the domains of trainer
      qualification, practice infrastructure and patient specific factors as well as
      mandatory criteria. The points scored through this system confer a variable
      period of authorization. Of the 30 participants 17 were satisfied with the period
      of authorization they received, 10 were dissatisfied, and one was indifferent.
      Satisfaction showed no correlation with sex, experience as a trainer, or with the
      score achieved through the criteria catalogue. It correlated little with the
      length of time practicing as a doctor. CONCLUSION: The criteria catalogue
      reflects both the breadth of general practice as well as the skills of the
      trainers. Satisfaction of participants in the test group was good, and infers a
      basis for applying the catalogue through regional medical associations to assign
      teaching practice status. It may also be used as a blue-print for other medical
      specialties.

PMID- 24575160
TI  - "Alcohol and nicotine"--Concept and evaluation of an interdisciplinary elective
      course with OSPE in preclinical medical education.
AB  - In the last decade, increasing interest has been paid to interdisciplinary and
      practical courses in the medical education in Germany. This report describes the
      implementation and outcome of a preclinical interdisciplinary elective course
      with a team-teaching concept developed by lecturers in medical psychology,
      anatomy, physiology and biochemistry. The practical orientation of the course led
      to the implementation of a final interdisciplinary OSPE to ensure fair
      consideration of the different disciplines involved in grading. Individual OSPE
      results correlate well with the fact that different skills are required in
      medical psychology compared to those required in anatomy, physiology and
      biochemistry. Student course evaluation and lecturers' experience indicate the
      success of this elective course. Its concept can be well adapted to other
      interdisciplinary courses. 

PMID- 24575161
TI  - Dynamic Switch Between Two Adhesion Phenotypes in Colorectal Cancer Cells.
AB  - The hematogenous metastatic cascade is mediated by the interaction of cancer
      cells and the endothelial cell lining of blood vessels. In this work, we examine
      the colon cancer cell line COLO 205, which grows simultaneously in both adherent
      and suspended states in culture and can serve as a good model for studying tumor
      heterogeneity. The two subpopulations of cells have different molecular
      characteristics despite being from the same parent cell line. We found that the
      ratio of adherent to suspended cells in culture is maintained at 7:3 (equilibrium
      ratio). The ratio was maintained even when we separate the two populations and
      culture them separately. After 8 h in culture the equilibrium was achieved only
      from either adherent or suspended population. The adherent cells were found to
      express less E-selectin binding glycans and demonstrated significantly weaker
      interaction with E-selectin under flow than the suspended cells. Manipulation of
      the epithelial-mesenchymal transition (EMT) markers beta-catenin and E-cadherin
      expression, either by siRNA knockdown of beta-catenin or incubation with E
      cadherin antibody-coated microbeads, shifted the ratio of adherent to suspended
      cells to 9:1. Interestingly, human plasma supplemented media shifted the ratio of
      adherent to suspended cells in the opposite direction to 1:9, favoring the
      suspended state. The dynamic COLO 205 population switch presents unique
      differential phenotypes of their subpopulations and could serve as a good model
      for studying cell heterogeneity and the EMT process in vitro.

PMID- 24575162
TI  - Necrobiosis Lipoidica Diabeticorum: A pediatric case report.
AB  - INTRODUCTION: Necrobiosis lipoidica (NL) is a rare chronic granulomatous
      dermatitis that usually appears in the lower extremities. It affects about 0.3
      1.2% of diabetic patients, the majority of whom have type 1 diabetes. The
      etiology and pathogenesis of this disorder are still unclear. NL is characterized
      by skin rash that usually affects the shins. The average onset is 30 years, with
      females being affected more commonly. There are very few reported cases of
      necrobiosis lipoidica in children. CASE REPORT: We report a case of a 16 year old
      girl affected by type 1 diabetes mellitus (15 years disease duration) who
      developed an erythematous nodular rash on the lower extremities and interscapular
      area. In the suspect of necrobiosis lipoidica, a skin biopsy was performed (lower
      extremities and interscapular area). The microscopic evaluation of the pretibial
      lesions was suggestive of necrobiosis lipoidica. The smaller lesions in the
      interscapular area showed signs of perivascular dermatitis which could be
      consistent with early stages of necrobiosis lipoidica. Local treatment with
      tacrolimus determined a progressive improvement of the lesions. CONCLUSION: In
      patients with T1DM, diagnosis of NL of the lower legs is usually unequivocal.
      However, diagnosis may be more challenging in the presence of lesions with recent
      onset and/or atypical clinical presentation and unusual site. In these cases, NL
      must always be taken in consideration in order to avoid misdiagnosis, wrong/late
      treatment decisions and progression to ulceration.

PMID- 24575163
TI  - Child Gender and Parental Investments In India: Are Boys And Girls Treated
      Differently?
AB  - Previous research has not always found that boys and girls are treated
      differently in rural India. However estimates of the effect of gender on parental
      investments could be biased if girls end up in larger families due to son-biased
      stopping rules. Using a novel identification strategy that exploits that gender
      at conception is random, we document that boys receive more childcare time than
      girls, they are breastfed longer and they get more vitamin supplementation.
      Compared to other developing countries, boys have an advantage in height and
      weight relative to girls. Neither greater needs nor anticipated family size
      explain the results.

PMID- 24575164
TI  - ?
AB  - Sexual stereotypes are beliefs that are generally accepted and are thought to
      define how men and women should express their sexuality. The objectives of this
      study were to identify how many heterosexual Puerto Rican men and women endorsed
      certain stereotypes about male and female sexuality and to explore the
      relationship between the endorsement of these sexual stereotypes and the
      attitudes towards condom use, as well as actual condom use during intercourse. We
      conducted a cross-sectional study in which we administered two scales, one about
      male sexuality and the other about female sexuality, to a group of 429
      heterosexual participants. We found that men endorsed significantly more male and
      female sexual stereotypes than women and that these tended to have a more
      conservative view of female sexuality than what they had of male sexuality.
      Women, on the other hand, tended to view female and male sexuality in a less
      stereotypical way. We also found that the more men and women endorsed male and
      female sexual stereotypes, the worse the attitudes toward condom use. However,
      endorsement of male and/or female sexual stereotypes was not related to condom
      use. These findings contradict the literature that suggests that these sexual
      stereotypes result in high-risk sexual conduct, which has important implications
      for the development and implementation of prevention programs.

PMID- 24575166
TI  - Oxidative stress and extracellular matrices after hepatectomy and liver
      transplantation in rats.
AB  - AIM: To investigate oxidative stress (OS)-mediated damage and the behavior of
      extracellular matrices in various rat models because shear stress with portal
      hypertension and cold ischemia/warm reperfusion injury trigger the liver
      regeneration cascade after surgery. These injuries also cause fatal liver damage.
      METHODS: Rats were divided into four groups according to the surgery performed:
      control; hepatectomy with 40% liver remnant (60% hepatectomy); orthotopic liver
      transplantation (OLT) with whole liver graft (100% OLT); and split OLT (SOLT)
      with 40% graft (40% SOLT). Survival was evaluated. Blood and liver samples were
      collected at 6 h after surgery. Biochemical and histopathological examinations
      were performed. OS-induced damage, 4-hydroxynonenal, ataxia-telangiectasia
      mutated kinase, histone H2AX, phosphatidylinositol 3-kinase (PI3K) and Akt were
      evaluated by western blotting. Behavior of extracellular matrices, matrix
      metalloproteinase (MMP)-9, MMP-2, tissue inhibitor of metalloproteinase (TIMP)-1
      and TIMP-2 were also evaluated by western blotting and zymography. RESULTS:
      Although 100% OLT survived, 60% hepatectomy and 40% SOLT showed poor survival.
      Histopathological, immunohistological, biochemical and protein assays revealed
      that 60% hepatectomy, 100% OLT and 40% SOLT showed liver damage. PI3K and Akt
      were decreased in 60% hepatectomy and 40% SOLT. For protein expression, 40% SOLT
      showed differences in MMP-9, MMP-2 and TIMP-2. TIMP-1 showed differences in 60%
      hepatectomy and 40% SOLT. For protein activity, MMP-9 demonstrated significant
      differences in 60% hepatectomy, 100% OLT and 40% SOLT. CONCLUSION: Under
      conditions with an insufficient liver remnant, prevention of OS-induced damage
      via the Akt/PI3K pathway may be key to improve the postoperative course. MMP-9
      may be also a therapeutic target after surgery.

PMID- 24575165
TI  - Portal vein thrombosis in liver cirrhosis.
AB  - Portal vein thrombosis (PVT) is considered to be a frequent complication of liver
      cirrhosis. However, unlike PVT in patients without cirrhosis, very few data are
      available on the natural history and management of PVT in cirrhosis, despite its
      association with potentially life-threatening conditions, such as
      gastroesophageal bleeding and acute intestinal ischemia. Moreover, no consensus
      regarding PVT in cirrhosis exists. Suggested causes of PVT in cirrhosis include
      reduced portal blood flow velocity, multiple congenital or acquired thrombophilic
      factors, inherited or acquired conditions, and derangement of liver architecture.
      However, the understanding of PVT in cirrhosis is incomplete. In addition,
      information on the management of PVT in cirrhosis is inadequate. The aims of this
      review are to: (1) assemble data on the physiopathological mechanism, clinical
      findings, diagnosis and management of PVT in cirrhosis; (2) describe the
      principal factors most frequently involved in PVT development; and (3) summarize
      the recent knowledge concerning diagnostic and therapeutic procedures. 

PMID- 24575167
TI  - Disease dependent qualitative and quantitative differences in the inflammatory
      response to ascites occurring in cirrhotics.
AB  - AIM: To assess differing patterns and levels of ascitic fluid cyctokine and
      growth factors exist between those with a high risk and low risk of spontaneous
      bacterial peritonitis (SBP). METHODS: A total of 57 consecutive patients with
      ascites requiring a large volume paracentesis were studied. Their age, gender,
      specific underlying disease conditions were recorded after a review of their
      clinical records. Each underwent a routine assessment prior to their paracentesis
      consisting of a complete blood count, complete metabolic profile and prothrombin
      time/international normalized ratio (INR) determination. The ascitic fluid was
      cultured and a complete cell count and albumin determination was obtained on the
      fluid. In addition, blood and ascitic fluid was assessed for the levels of
      interleukin interleukin (IL)-1A, IL-1B, IL-2, IL-4, IL-8, IL-10, monocyte
      chemotactic protein (MCP)-1, tumor necrosis factor (TNF)-alpha, interferon (IFN)
      gamma, vascular endothelial growth factor (VEGF) and epidermal growth factor
      (EGF) utilizing the Randox Biochip platforms (Boston, MA). A serum-ascites
      gradient, for each cytokine and growth factor was calculated. The results are
      reported as mean +/- SEM between disease groups with statistical analysis
      consisting of the student t-test (two tailed) with a P value of 0.05 defining
      significance. RESULTS: No clinically important demographic or biochemical
      differences between the 4 groups studied were evident. In contrast, marked
      difference in the cytokine and growth factors levels and pattern were evident
      between the 4 disease groups. Individuals with alcoholic cirrhosis had the
      highest levels of IL-1A, IL-1B, IL-4, IFNgamma. Those with malignant disease had
      the highest levels of IL-2. Those with hepatitis C virus (HCV) associated
      cirrhosis had the highest value for IL-6, IL-8, IL-10, MCP-1 and VEGF. Those with
      cardiac disease had the highest level of TNF-alpha and EGF. The calculated serum-
      ascites gradients for the cardiac and malignant disease groups had a greater
      frequency of negative values signifying greater levels of IL-8, IL-10 and MCP-1
      in ascites than did those with alcohol or HCV disease. CONCLUSION: These data
      document important differences in the cytokine and growth factor levels in
      plasma, ascitic fluid and the calculated plasma - ascites fluid gradients in
      cirrhotics requiring a large volume paracentesis. These differences may be
      important in determining the risk for bacterial peritonitis.

PMID- 24575168
TI  - Association between inherited monogenic liver disorders and chronic hepatitis C.
AB  - AIM: To determine the frequencies of mutations that cause inherited monogenic
      liver disorders in patients with chronic hepatitis C. METHODS: This study
      included 86 patients with chronic hepatitis C (55 men, 31 women; mean age at
      diagnosis, 38.36 +/- 14.52 years) who had undergone antiviral therapy comprising
      pegylated interferon and ribavirin. Viral load, biochemical parameter changes,
      and liver biopsy morphological data were evaluated in all patients. The control
      group comprised 271 unrelated individuals representing the general population of
      Latvia for mutation frequency calculations. The most frequent mutations that
      cause inherited liver disorders [gene (mutation): ATP7B (H1069Q), HFE (C282Y,
      H63D), UGT1A1 (TA)7, and SERPINA1 (PiZ)] were detected by polymerase chain
      reaction (PCR), bidirectional PCR allele-specific amplification, restriction
      fragment length polymorphism analysis, and sequencing. RESULTS: The viral
      genotype was detected in 80 of the 86 patients. Viral genotypes 1, 2, and 3 were
      present in 61 (76%), 7 (9%), and 12 (15%) patients, respectively. Among all 86
      patients, 50 (58%) reached an early viral response and 70 (81%) reached a
      sustained viral response. All 16 patients who did not reach a sustained viral
      response had viral genotype 1. Case-control analysis revealed a statistically
      significant difference in only the H1069Q mutation between patients and controls
      (patients, 0.057; controls, 0.012; odds ratio, 5.514; 95%CI: 1.119-29.827, P =
      0.022). However, the H1069Q mutation was not associated with antiviral treatment
      outcomes or biochemical indices. The (TA) 7 mutation of the UGT1A1 gene was
      associated with decreased ferritin levels (beta regression coefficient = -295.7,
      P = 0.0087). CONCLUSION: Genetic mutations that cause inherited liver diseases in
      patients with hepatitis C should be studied in detail.

PMID- 24575169
TI  - Methylsulfonylmethane suppresses hepatic tumor development through activation of
      apoptosis.
AB  - AIM: To investigate the effect of methylsulfonylmethane (MSM), recently reported
      to have anti-cancer effects, in liver cancer cells and transgenic mice. METHODS:
      Three liver cancer cell lines, HepG2, Huh7-Mock and Huh7-H-ras (G12V), were used.
      Cell growth was measured by Cell Counting Kit-8 and soft agar assay. Western blot
      analysis was used to detect caspases, poly (ADP-ribose) polymerase (PARP), and B
      cell lymphoma 2 (Bcl-2) expressions. For in vivo study, we administered MSM to H
      ras (12V) transgenic mice for 3 mo. RESULTS: MSM decreased the growth of HepG2,
      Huh7-Mock and Huh7-H-ras (G12V) cells in a dose-dependent manner. That was
      correlated with significantly increased apoptosis and reduced cell numbers in MSM
      treated cells. Cleaved caspase-8, cleaved caspase-3 and cleaved PARP were
      remarkably increased in the liver cancer cells treated with 500 mmol/L of MSM;
      however, Bcl-2 was slightly decreased in 500 mmol/L. Liver tumor development was
      greatly inhibited in the H-ras (12V) transgenic mice treated with MSM, compared
      to control, by showing reduced tumor size and number. Cleaved PARP was
      significantly increased in non-tumor treated with MSM compared to control.
      CONCLUSION: Liver injury was also significantly attenuated in the mice treated
      with MSM. Taken together, all the results suggest that MSM has anti-cancer
      effects through inducing apoptosis in liver cancer.

PMID- 24575170
TI  - Pattern of failure after high-dose thoracic radiation for non-small cell lung
      cancer: the University of Michigan experience.
AB  - PURPOSE: Our main purpose is to study the pattern of local failure for patients
      with non-small cell lung cancer treated with conformal therapy. METHODS: This
      study included patients who failed locally and a matched group without failures
      after 3D conformal radiation per a radiation dose-escalation trial. Radiation
      doses ranged from 65.1 to 102.9 Gy in 2.1 Gy fractions, originally computed using
      an equivalent path length algorithm. The recurrent gross target volumes (RGTV)
      were contoured. The original and recurrent planning target volume (PTV and RPTV)
      were generated by 1 cm uniform expansion from GTV. DVHs and generalized
      equivalent uniform doses (EUD={Sigma i (di ) a }1/a ) were computed. Marginal
      failures were defined for RGTVs covered by the original 10 to 90 % isodose
      surfaces. RESULTS: There were no significant differences between the failed and
      control groups with regard to average original GTV volumes, GTV and PTV doses,
      and minimum PTV doses. Of the 18 RGTVs, four had marginal failure, 12 failed
      mostly within, and two failed outside of the original PTV. The mean EUDs were
      57.1 Gy (95 % confidence interval (CI) 43.9-70.6) and 47.5 Gy (95 % CI 33.7
      61.2), for the RGTVs and RPTVs, respectively, significantly below the prescribed
      doses (p=0.03). EUDs were less than 60 Gy for 39 % of the RGTVs and 56 % of the
      RPTVs. CONCLUSIONS: Recurrent tumors had significantly lower doses than the
      prescribed dose suggesting that some of these failures could have been avoided
      with modern technology such as 4D CT simulation and image-guided radiation
      therapy.

PMID- 24575171
TI  - Hypertrophic cardiomyopathy in 2013: Current speculations and future
      perspectives.
AB  - Hypertrophic cardiomyopathy (HCM), the most variable cardiac disease in terms of
      phenotypic presentation and clinical outcome, represents the most common
      inherited cardiomyopathic process with an autosomal dominant trait of
      inheritance. To date, more than 1400 mutations of myofilament proteins associated
      with the disease have been identified, most of them "private" ones. This striking
      allelic and locus heterogeneity of the disease certainly complicates the
      establishment of phenotype-genotype correlations. Additionally, topics pertaining
      to patients' everyday lives, such as sudden cardiac death (SCD) risk
      stratification and prevention, along with disease prognosis, are grossly related
      to the genetic variation of HCM. This review incorporates contemporary research
      findings and addresses major aspects of HCM, including preclinical diagnosis,
      genetic analysis, left ventricular outflow tract obstruction and SCD. More
      specifically, the spectrum of genetic analysis, the selection of the best method
      for obstruction alleviation and the need for a unique and accurate factor for SCD
      risk stratification are only some of the controversial HCM issues discussed.
      Additionally, future perspectives concerning HCM and myocardial ischemia, as well
      as atrial fibrillation, are discussed. Rather than enumerating clinical studies
      and guidelines, challenging problems concerning the disease are critically
      appraised by this review, highlighting current speculations and recommending
      future directions. 

PMID- 24575174
TI  - Infiltrative cardiac lymphoma with tricuspid valve involvement in a young man.
AB  - Cardiac metastases are among the topics with limited systematic reviews.
      Theoretically, the heart can be infiltrated by any malignancy with the ability to
      spread to distant structures. Thus far, no specific tumors are known to have a
      predilection for the heart, but some do metastasize more often than others, for
      example, melanoma and primary mediastinal tumors. We report a case of cardiac
      metastasis from a diffuse large B cell lymphoma in a young man. The peculiarity
      of this case is that besides the involvement of right ventricle and atrium, the
      tricuspid valve was also infiltrated. Valvular metastasis is rarely reported in
      the medical literature. 

PMID- 24575176
TI  - Ecological Characteristics of a Gonystylus bancanus-rich Area in Pekan Forest
      Reserve, Pahang, Malaysia.
AB  - Tropical peat swamp forest (PSF) is a unique wetland ecosystem with distinct
      vegetation types. Due to the waterlogged environment, the stand characteristics
      in this ecosystem are different from those of other inland forests. This paper
      highlights stand characteristics of a PSF based on our investigation of a 1 ha
      ecological plot established in a Virgin Jungle Reserve (VJR) at Compartment 100,
      Pekan Forest Reserve, Pahang, Malaysia. This site is considered a Gonystylus
      bancanus-rich area. From the inventory, we recorded a total of 49 tree species
      from 38 genera and 25 families among all trees of >= 10 cm in diameter at breast
      height. Calophyllum ferrugineum var. ferrugineum was the most abundant species,
      followed by G. bancanus. The forest appeared healthy, as all tree characteristics
      (crown shape, log grade and climber infestation) generally fell within Classes 1
      and 2 (good and moderate categories), with the exception of crown illumination
      which majority of the trees were rated as class 3 (received less sunlight). The
      latter finding indicates that most of the trees living under the canopy received
      minimal illumination. In terms of total tree biomass, we estimated that about
      414.6 tonnes exist in this 1 ha area; this tree biomass is higher than in some
      PSF areas of Sumatra, Indonesia. 

PMID- 24575175
TI  - Cloning and Characterisation of (R)-3-hydroxyacyl-acyl Carrier Protein-coenzyme A
      Transferase Gene (phaG) from Pseudomonas sp. USM 4-55.
AB  - The (R)-3-hydroxyacyl-ACP-CoA transferase catalyses the conversion of (R)-3
      hydroxyacyl-ACP to (R)-3-hydroxyacyl-CoA derivatives, which serves as the
      ultimate precursor for polyhydroxyalkanoate (PHA) polymerisation from unrelated
      substrates in pseudomonads. PhaG was found to be responsible for channelling
      precursors for polyhydroxyalkanoate (PHA) synthase from a de novo fatty acid
      biosynthesis pathway when cultured on carbohydrates, such as glucose or
      gluconate. The phaG gene was cloned from Pseudomonas sp. USM 4-55 using a
      homologous probe. The gene was located in a 3660 bp Sal I fragment (GenBank
      accession number EU305558). The open reading frame (ORF) was 885 bp long and
      encoded a 295 amino acid protein. The predicted molecular weight was 33251 Da,
      and it showed a 62% identity to the PhaG of Pseudomonas aeruginosa. The function
      of the cloned phaG of Pseudomonas sp. USM 4-55 was confirmed by complementation
      studies. Plasmid pBCS39, which harboured the 3660 bp Sal I fragment, was found to
      complement the PhaG-mutant heterologous host cell, Pseudomonas putida PhaGN-21.
      P. putida PhaGN-21, which harboured pBCS39, accumulated PHA that accounted for up
      to 18% of its cellular dry weight (CDW). P. putida PhaGN-21, which harboured the
      vector alone (PBBR1MCS-2), accumulated only 0.6% CDW of PHA. 

PMID- 24575173
TI  - Therapeutic interventions for heart failure with preserved ejection fraction: A
      summary of current evidence.
AB  - Heart failure with preserved ejection fraction (HFPEF) is common and represents a
      major challenge in cardiovascular medicine. Most of the current treatment of
      HFPEF is based on morbidity benefits and symptom reduction. Various
      pharmacological interventions available for heart failure with reduced ejection
      fraction have not been supported by clinical studies for HFPEF. Addressing the
      specific aetiology and aggressive risk factor modification remain the mainstay in
      the treatment of HFPEF. We present a brief overview of the currently recommended
      therapeutic options with available evidence. 

PMID- 24575177
TI  - Fish assemblages in streams subject to anthropogenic disturbances along the
      natchez trace parkway, Mississippi, USA.
AB  - A three-year study (July 2000 - June 2003) of fish assemblages was conducted in
      four tributaries of the Big Black River: Big Bywy, Little Bywy, Middle Bywy and
      McCurtain creeks that cross the Natchez Trace Parkway, Choctaw County,
      Mississippi, USA. Little Bywy and Middle Bywy creeks were within watersheds
      influenced by the lignite mining. Big Bywy and Middle Bywy creeks were
      historically impacted by channelisation. McCurtain Creek was chosen as a
      reference (control) stream. Fish were collected using a portable backpack
      electrofishing unit (Smith-Root Inc., Washington, USA). Insectivorous fish
      dominated all of the streams. There were no pronounced differences in relative
      abundances of fishes among the streams (P > 0.05) but fish assemblages fluctuated
      seasonally. Although there were some differences among streams with regard to
      individual species, channelisation and lignite mining had no discernable adverse
      effects on functional components of fish assemblages suggesting that fishes in
      these systems are euryceous fluvial generalist species adapted to the variable
      environments of small stream ecosystems. 

PMID- 24575178
TI  - Checklist and Simple Identification Key for Frogs and Toads from District IV of
      The MADA Scheme, Kedah, Malaysia.
AB  - A survey was conducted to catalogue the diversity of anurans in District IV of
      the Muda Agriculture Development Authority Scheme (MADA) in Kedah Darul Aman,
      Malaysia, from July 1996 to January 1997. Eight species of anurans from three
      families were present in the study area. Of these, the Common Grass Frog
      (Fejevarya limnocharis) was the most abundant, followed by Mangrove Frog
      (Fejevarya cancrivora), Long-legged Frog (Hylarana macrodactyla), and Common Toad
      (Duttaphrynus melanostictus). Puddle Frog (Occidozyga lima), Taiwanese Giant Frog
      (Hoplobatrachus rugulosus), and Banded Bullfrog (Kaluola pulchra) were rare
      during the sampling period, and only one Paddy Frog (Hylarana erythraea) was
      captured. A simple identification key for the anurans of this area is included
      for use by scientists and laymen alike. 

PMID- 24575179
TI  - Freshwater fishes of gunung jerai, kedah darul aman: a preliminary study.
AB  - A total of 37 fish species from 14 families were observed during surveys
      conducted from January to March 2005 at 8 selected streams near the Gunung Jerai
      Forest Reserve. The list includes two species (Rasbora trilineata and Systomus
      partipentazona) that were visually identified at the lower part of the Sungai
      Teroi stream. Single specimens of Leiocassis micropogon, Clarias macrocephalus
      and Hampala macrolepidota were also obtained at certain sampling stations.
      Devario regina and Systomus binotatus were the most abundant species at all
      sampling stations. However, the list is still incomplete as the study was carried
      out over a short time period and there are large areas that have not yet been
      surveyed. The presence of exotic species (Carassius auratus) at Sungai Badak
      indicates anthropogenic influences. Therefore, a long-term monitoring program for
      Gunung Jerai Forest Reserve streams should be planned and carried out to assess
      the impacts of future development on fish biodiversity and water quality. 

PMID- 24575180
TI  - Microbial Inoculation Improves Growth of Oil Palm Plants (Elaeis guineensis
      Jacq.).
AB  - Introduction of diazotrophic rhizobacteria to oil palm tissues during the in
      vitro micropropagation process establishes an early associative interaction
      between the plant cells and bacteria. In the association, the diazotrophs provide
      the host plants with phytohormones and fixed nitrogen. This study was conducted
      to observe growth of bacterised tissue cultured oil palm plants under ex vitro
      conditions after 280 days of growth. Root dry weight, shoot dry weight, root
      volume, bacterial colonisation, leaf protein and chlorophyll content of the host
      plants were observed. The results revealed that the inocula successfully
      colonised roots of the host plants. Plants inoculated with Acetobacter
      diazotrophicus (R12) had more root dry weight and volume than plants inoculated
      with Azospirillum brasilense (Sp7). Leaf protein and chlorophyll content were
      higher in the bacterised plants compared to Control 2 plants (inoculated with
      killed Sp7). These results suggest that the diazotrophs successfully improved the
      growth of the host plant (oil palm) and minimised the amount of N fertiliser
      necessary for growth. 

PMID- 24575181
TI  - Analytical approaches for addressing the variation in back-calculated age-length
      relationships for fish.
AB  - Estimating an age-length relationship is a routine aspect of many fisheries
      studies and is simplified by the use of commercially available computer programs.
      These computer programs may be misleading since a result can be produced
      irrespective of the quality or the extent of the data, and there is some concern
      that back-calculated age-length relationships are sensitive to the sample size
      and composition. We investigated this issue by comparing estimates of mean back
      calculated lengths at age and growth rates derived from subsets of a large sample
      of wild channel catfish Ictalurus punctatus (N=788) collected in 2001 and 2002
      from 9 rivers in Mississippi, United States. Estimates of growth rate varied
      among subsets consisting of individual year class (2-6) of channel catfish
      separated from the overall sample. For nine subsets, comprising randomly-selected
      and increasing proportions of the overall sample (20%-100% at 10% increments of
      the overall sample), growth was similar. However, growth differed for a subset
      representing a random 10% of the overall sample. Lengths at age and growth rates
      derived from each of the 2001 and 2002 components of the sample both differed.
      All results were significant at P < 0.05. 

PMID- 24575172
TI  - The role of nutrition and nutraceutical supplements in the treatment of
      hypertension.
AB  - Vascular biology, endothelial and vascular smooth muscle and cardiac dysfunction
      play a primary role in the initiation and perpetuation of hypertension,
      cardiovascular disease and target organ damage. Nutrient-gene interactions and
      epigenetics are predominant factors in promoting beneficial or detrimental
      effects in cardiovascular health and hypertension. Macronutrients and
      micronutrients can prevent, control and treat hypertension through numerous
      mechanisms related to vascular biology. Oxidative stress, inflammation and
      autoimmune dysfunction initiate and propagate hypertension and cardiovascular
      disease. There is a role for the selected use of single and component
      nutraceutical supplements, vitamins, antioxidants and minerals in the treatment
      of hypertension based on scientifically controlled studies which complement
      optimal nutrition, coupled with other lifestyle modifications. 

PMID- 24575182
TI  - Facultative Apomixis in Garcinia atroviridis (Clusiaceae) and Effects of
      Different Pollination Regimes on Reproductive Success.
AB  - Various aspects of the reproductive success of Garcinia atroviridis Griff. were
      studied. Controlled pollination experiments were carried out in an orchard
      located in Songkhla province, southern Thailand, from February to July 2003.
      Floral longevity, stigma receptivity, and pollen viability were examined before
      carrying out the experiments. Three pollination treatments were compared: open
      pollination, manual pollination with bags, and bags without pollination
      (apogamy). Although there was no significant difference in the initial fruit set,
      bagged and manual pollination produced a significantly greater fruit drop rate
      than apogamy or natural pollination at one week after the flowers had been
      pollinated. On the other hand, the apogamy treatment had a greater fruit drop
      rate than natural and manual pollination treatments before fruit maturation. In
      addition, unpollinated bagged flowers bore fewer and smaller fruit than naturally
      and manually cross-pollinated flowers. Although the fruits from unpollinated
      flowers were capable of asexual seed formation, they produced fewer seeds and had
      poorer seed quality (defined as average fresh weight and germination rate) than
      those from the other treatments. The occurrence of asexual and sexual
      reproduction was also studied using Random Amplification of Polymorphic DNA
      (RAPD) analysis and by comparing the patterns of bands produced from DNA
      extracted from the offspring of the naturally cross-pollinated fruits. On
      average, 58% of the offspring had a genetic constitution identical to that of the
      maternal parent (ranging from 36% to 87%), indicating that some offspring were
      produced without prior fertilisation. However, the remainder showed polymorphism,
      demonstrating the occurrence of sexual reproduction. These findings indicate that
      facultative apomixis occurred in the study population. However, a residual
      sexuality was important for fruit production, fruit size, normal seed set and
      seed quality. 

PMID- 24575183
TI  - Preliminary Screening of Antibacterial Activity Using Crude Extracts of Hibiscus
      rosa sinensis.
AB  - Hibiscus rosa sinensis, a member of the Malvaceae family, is widely cultivated in
      the tropics as an ornamental plant. It is often planted as a fence or hedge
      plant, and has several forms of flowers with varying colours. It is also used in
      traditional medicine to induce abortion, ease menstrual cramps, assist in
      childbirth and relieve headache, fever and inflammation. In this study, we
      evaluated the antibacterial activity of H. rosa sinesis extract using a disc
      diffusion method. Crude petroleum ether extract, ethyl acetate extract and
      methanol extract from the leaves, stems and flowers of the plant were prepared
      using a cold extraction technique. These extracts were tested at concentrations
      ranging from 4 mg/disc to 0.017 mg/disc against methicillin-resistant
      Staphylococcus aureus (MRSA), Staphylococcus aureus, Escherichia coli,
      Pseudomonas aeruginosa and Klebsiella pneumonia. The petroleum ether extract from
      the leaves, stems and flowers and methanol extract from the leaves showed
      inhibition zones with diameters > 12 mm against MRSA. Overall, the petroleum
      ether extract from flowers at concentrations of 4 mg/disc and 2 mg/disc displayed
      the strongest inhibition zones of 18.6 +/- 2.85 mm and 18.5 +/- 0.29 mm,
      respectively, as compared to vancomycin (30 MUg/ml), which did not differ
      significantly from the 18.0 +/- 0.10 mm size of the vancomycin (30 MUg/ml)
      inhibition zone (p < 0.05). In conclusion, H. rosa sinensis extract is a
      potential antibacterial agent for treating MRSA infection. 

PMID- 24575184
TI  - Characterisation of colletotrichum species associated with anthracnose of banana.
AB  - A total of 13 Colletotrichum isolates were obtained from different banana
      cultivars (Musa spp.) with symptoms of anthracnose. Colletotrichum isolates from
      anthracnose of guava (Psidium guajava) and water apple (Syzygium aqueum) were
      also included in this study. Based on cultural and morphological characteristics,
      isolates from banana and guava were identified as Colletotrichum musae and from
      water apple as Colletotrichum gloeosporiodes. Isolates of C. musae from banana
      and guava had similar banding patterns in a randomly amplified polymorphic DNA
      (RAPD) analysis with four random primers, and they clustered together in a UPGMA
      analysis. C. gloeosporiodes from water apple was clustered in a separate cluster.
      Based on the present study, C. musae was frequently isolated from anthracnose of
      different banana cultivars and the RAPD banding patterns of C. musae isolates
      were highly similar but showed intraspecific variations. 

PMID- 24575185
TI  - Natural Occurrence of Toxigenic Fusarium proliferatum on Paddy (Oryza sativa L.)
      in Karnataka, India.
AB  - Contamination of paddy seeds (rice with husk) by Fusarium species can cause
      spoilage and subsequent production of mycotoxins, especially fumonisins that
      affect human and animal health. A mycological study was conducted to evaluate the
      natural occurrence of fumonisin B1 produced by Fusarium proliferatum on paddy
      grown in different geographic regions of Karnataka (India). A total of 65
      isolates of F. proliferatum from paddy samples were analysed by polymerase chain
      reaction (PCR). One set of primers, Fp3-F and Fp4-R was employed to identify the
      species F. proliferatum, and another set of primers, FUM1 was employed to
      determine the fumonisin producing ability of the isolates. All 65 isolates of F.
      proliferatum scored positive with both set of primers, producing amplified
      products of the expected sizes. Furthermore, thin layer chromatography (TLC)
      analysis detected fumonisin B1 (FB1) in all of the PCR positive isolates of F.
      proliferatum. 

PMID- 24575186
TI  - Spore Density and Viability of Entomopathogenic Fungal Isolates from Indonesia,
      and Their Virulence against Aphis gossypii Glover (Homoptera: Aphididae).
AB  - The focus of this study was on quantifying fitness attributes, such as spore
      density and viability, and determining the virulence level against aphid (Aphis
      gossypii) nymphs of isolates from the fungal species Beauveria bassiana and
      Metarhizium anisopliae. The fungal isolates were obtained from several insects,
      including Plutella xylostella, Hypothenemus hampei, Bronstispa longissima, A.
      gossypii, Tenebrio molitor, and Leptocorisa acuta, that were collected from
      Indonesian islands, such as Sumatera, Java, and Sulawesi. Third instar aphid
      nymphs were inoculated via topical application of 10(6) conidia ml(-1) of the
      entomopathogenic fungal isolates. All of the B. bassiana and M. anisopliae
      isolates could produce very dense spores. The M. anisopliae isolate MaAg, which
      was obtained from the aphid, had the highest spore density at 6.70 * 10(8)
      conidia ml(-1). Among the B. bassiana isolates, the highest conidial viability
      belonged to isolate CPJW8, which was obtained from Chrysodeixis chalcites, with a
      39% average viability. Among the M. anisopliae isolates, the highest viabilities
      belonged to the isolates MaAg and MaLa, which were obtained from L. acuta, with a
      33% and 32% average viabilities, respectively. All of the B. bassiana and M.
      anisopliae isolates were virulent against aphid nymphs, with mortality rates
      ranging from 64% to 94%. The three most virulent isolates were BBY715 (94%), MPx
      (92%), and MaTm (92%), and the least virulent isolate was MaLa (64%). BBY715, the
      most virulent isolate, had the shortest lethal time median (LT50) against aphid
      nymphs at 2.97 hours, and MaLa had the longest LT50 at 61.81 hours. 

PMID- 24575187
TI  - Fusarium species isolated from mangrove soil in kampung pantai acheh, balik
      pulau, pulau pinang, malaysia.
AB  - A total of 33 isolates of Fusarium sp. were isolated from soil samples collected
      from a mangrove forest in an area in Kampung Pantai Acheh, Balik Pulau, Pulau
      Pinang, Malaysia. The isolates were isolated using soil dilution, direct
      isolation and debris isolation techniques. The debris isolation technique yielded
      the most isolates, with a total of 22 Fusarium isolates. Based on identification
      using morphological characteristics, three Fusarium species were identified: F.
      solani, F. oxysporum and F. verticillioides. F. solani (91%) was the most common
      species recovered from the mangrove soil samples, followed by F. oxysporum (6%)
      and F. verticillioides (3%). 

PMID- 24575188
TI  - Identification of Chromosomal Aberrations by Using Trypsin G-banding in
      Hepatocellular Carcinoma Patients (HCC) in Tamil Nadu, India.
AB  - Hepatocellular carcinoma (HCC) (or liver cancer) is one of the most common human
      malignancies worldwide. Aetiologically, HCC is closely associated with chronic
      hepatitis B and C virus infection, cirrhosis and alcohol intake. The objective of
      the present study was to elucidate the chromosomal abberations (CA) in HCC
      patients using the trypsin G-banding technique. This study may help in
      understanding the pattern of the disease and to assess whether these aberrations
      are associated with HCC susceptibility. The study examined 51 HCC cases and an
      equal number (n = 51) of age and gender matched cancer-free controls recruited
      from the hospitals in Tamil Nadu. The HCC cases were grouped depending upon their
      age into group I (<= 45 years) and group II (>= 46 years). The development of
      effective markers for the detection of HCC could have an impact on cancer
      mortality and may have significant public health implications worldwide. Subjects
      were recruited based on their alpha-fetoprotein (AFP) serum level, which is an
      effective marker for HCC. In the HCC cases, a higher number of chromatid
      aberrations [group I 13(25.5%) and group II 43(84.3%)] and CA [group I 10(19.6%)
      and group II 28(54.9%)] were observed. In contrast, controls showed a lower
      number of chromatid [group I 5(9.8%) and group II 12(23.5%)] and CA [group I
      4(7.8%) and group II 9(17.6%)]. In conclusion, the results of this study
      contribute to the validation of CA as an intermediate end point in
      carcinogenesis. Because many people are unaware of this lethal disease, this
      study will raise awareness of this cancer. 

PMID- 24575189
TI  - The Stability of rRNA in Heat-killed Salmonella enterica Cells and Its Detection
      by Fluorescent In Situ Hybridisation (FISH).
AB  - Differentiation of viable cells from non-viable cells is a major concern in the
      detection of foodborne microbial pathogens. Fluorescent in situ hybridisation
      (FISH) has been utilised as a promising method in this regard. The ability of
      FISH to differentiate viable cells from non-viable cells depends on the rapid
      degradation of rRNA in non-viable cells. In our work, Salmonella enterica that
      were heat-killed at 80 degrees C, 100 degrees C and 121 degrees C were examined
      for the presence of rRNA using FISH at various times ranging from 5 minutes to 48
      hours after heat treatment. rRNA was detected by FISH in heat-killed bacteria for
      12 hours, 3 hours and 1 hour after treatment at 80 degrees C, 100 degrees C and
      121 degrees C, respectively. These results indicate that there is a correlation
      between temperature and stability of rRNA in heat-killed bacteria. In conclusion,
      FISH was determined to be a suitable method for differentiation of viable cells
      from non-viable cells, especially for samples subjected to extreme heat. 

PMID- 24575190
TI  - Effects of Arbuscular Mycorrhization in Sterile and Non-sterile Soils.
AB  - Mycorrhiza, a mutualistic association between fungi and higher plants, has been
      documented extensively, but much less is known about the development of
      arbuscular mycorrhizal (AM) fungi and their effects on the growth of peanuts
      (Arachis hypogea L.). Therefore, the mycorrhizal status of Glomus spp. was
      investigated in the following diverse substrate soil conditions: non-autoclaved
      soil, autoclaved soil and autoclaved soil plus soil microbiota. The results
      indicated that both the arbuscular mycorrhizae, Glomus mosseae (Nicol. & Gerd.)
      Gerd. & Trappe, and Glomus fasciculatum (Thaxter) Gerd. & Trappe emend. Walker &
      Koske were infective to peanut, but displayed a differential impact on peanut
      growth depending on the microbial biomass content of the substrate soils. G.
      mosseae proved to be the most effective at improving peanut growth. 

PMID- 24575191
TI  - Herpetofauna of gunung panti forest reserve, johor, peninsular malaysia.
AB  - A survey was carried out at Gunung Panti Forest Reserve, Johor from 3-7 August
      2006, 2-5 June 2008, and 28-31 July 2008 to inventory the herpetofauna therein.
      An updated checklist for the area which incorporates findings from previous
      studies is provided. In total, 37 species of frogs, 1 turtle, 27 lizards, and 11
      snakes have been recorded from Gunung Panti Forest Reserve, Johor. 

PMID- 24575192
TI  - The Use of Per Recruit Models for Stock Assessment and Management of Greasy
      Grouper Epinephelus tauvina in The Arabian Gulf Waters off Qatar.
AB  - Per recruit models were applied to assess greasy grouper, Epinephelus tauvina,
      stock in the gulf waters off Qatar. Yield per recruit (Y/R) increased rapidly at
      low values of fishing mortality (F). At present natural mortality (M = 0.17 per
      year) and age at first capture (Tc = 7.6 years), the Y/R increased with
      increasing F to reach a maximum value of 1067.8 g per recruit at F = 0.65 per
      year. Above this level of F, Y/R was constant or slightly decreased. The current
      level of F is higher than the biological reference points F0.1 (0.15 per year),
      FSB40% (0.13 per year), FSB50% (0.08 per year) and FSB25% (0.24 per year).
      Increasing the Tc by one year resulted in a slight increase in the Y/R, while
      additional increases in Tc led to a decrease in Y/R values. At constant M, the
      increase in Tc caused an increase in F required to obtain the maximum Y/R until
      reaching a non-maximum state at the oldest Tc. At the current level of F,
      increasing the Tc by one year would result in a small increase in biomass per
      recruit (B/R), while further increases would lead to a decrease in B/R. At higher
      levels of F, any increase in Tc would cause a gradual increase in B/R, followed
      by a decline after a certain value of Tc. These results provide evidence of
      recruitment over-fishing at all optimum fishing levels, F0.1, FSB40%, FSB50% and
      at the threshold level, FSB25%. Therefore, sustainable management and
      conservation of greasy grouper in Qatari waters would require a decrease in F to
      levels less than F0.1 and FSB40%, which can be achieved through a reduction in
      fishing effort but not through an increase in Tc. 

PMID- 24575193
TI  - The use of principal component and cluster analysis to differentiate banana peel
      flours based on their starch and dietary fibre components.
AB  - Banana peel flour (BPF) prepared from green or ripe Cavendish and Dream banana
      fruits were assessed for their total starch (TS), digestible starch (DS),
      resistant starch (RS), total dietary fibre (TDF), soluble dietary fibre (SDF) and
      insoluble dietary fibre (IDF). Principal component analysis (PCA) identified that
      only 1 component was responsible for 93.74% of the total variance in the starch
      and dietary fibre components that differentiated ripe and green banana flours.
      Cluster analysis (CA) applied to similar data obtained two statistically
      significant clusters (green and ripe bananas) to indicate difference in
      behaviours according to the stages of ripeness based on starch and dietary fibre
      components. We concluded that the starch and dietary fibre components could be
      used to discriminate between flours prepared from peels obtained from fruits of
      different ripeness. The results were also suggestive of the potential of green
      and ripe BPF as functional ingredients in food. 

PMID- 24575194
TI  - Endophytic fungi from paddy.
AB  - Endophytic fungi were isolated from different parts of healthy paddy plants
      (Oryza sativa). The most common endophytic fungal genus recovered was Fusarium,
      followed by Aspergillus, Curvularia, Penicillium, Gilmaniella and Arthrobotrys
      foliicola. Fusarium and Curvularia had higher occurrences in the seeds compared
      with the other fungi. Aspergillus was recovered mostly from leaf blades and
      Penicillium from the leaf sheath. Gilmaniella and A. foliicola were isolated only
      from the roots and leaf blade, respectively. The assemblage of endophytic fungi
      in healthy tissues of paddy plants may indicate that some of the fungi are
      possible latent pathogens and some may become saprophytic. 

PMID- 24575195
TI  - Studies on Monstereae (Araceae) of Peninsular Malaysia I: Rhaphidophora
      megasperma, a New Record for West Malaysia.
AB  - Rhaphidophora megasperma Engl., a species hitherto regarded as endemic to
      Sarawak, East Malaysia, is published as a new record for Peninsular Malaysia. It
      is the first species in the Rhaphidophora Spathacea group recorded for western
      Sunda. The species is illustrated and a key to the perforate-laminated
      Rhaphidophora in Peninsular Malaysia is presented. 

PMID- 24575196
TI  - Bird species composition and feeding guilds based on point count and mist netting
      methods at the paya indah wetland reserve, peninsular malaysia.
AB  - A comparison study was conducted to determine the bird species composition,
      relative abundance, species diversity and feeding guilds based on point count
      (PC) and mist netting (MN) at the Paya Indah Wetland Reserve (PIWR), Peninsular
      Malaysia. A total of 13872 bird observations belonging to 100 species and 38
      families were recorded using the PC method over 15 consecutive months, and a
      total of 1478 bird individuals belonging to 65 species and 33 families were
      captured using the MN method over 1260 netting hours. The results showed that
      Treron vernans (1723 observations; 12.42%) was the most abundant bird species
      using the PC method, whereas Pycnonotus goiavier (378 individuals; 25.64%) was
      the most abundant bird species using the MN method. The Ardeidae (9 species;
      23.68%) was the most dominant family using the PC method, but the Rallidae (6
      species; 18.18%) was the most dominant family using the MN method. The PC method
      produced higher species diversity (Shannon's N1 = 31.22) and richness (Margalef's
      R1 = 10.42) than MN, whereas the MN method produced higher species evenness
      (McIntosh's E = 0.86) than the PC method. Frugivore/insectivore comprised of
      bulbuls, orioles, pigeons and starlings was the most dominant feeding guild in
      both methods (PC = 27.81% and MN = 32.88%). In contrast, carnivore was the rarest
      feeding guild in both methods (i.e. PC = 0.17% and MN = 0.20%). These findings
      indicate that the PC method is more efficient and produces better results than
      the MN method. 

PMID- 24575197
TI  - Morphological Study of the Relationships between Weedy Rice Accessions (Oryza
      sativa Complex) and Commercial Rice Varieties in Pulau Pinang Rice Granary Area.
AB  - Weedy rice (WR) is found in many direct-seeded rice fields. WR possesses
      morphological characteristics that are similar to cultivated rice varieties in
      the early stage of growth, making them more difficult to control than other
      weeds. A comparative morphological study was conducted by collecting WR
      accessions from four sites within the Pulau Pinang rice growing areas. The
      objective of the study was to characterise WR accessions of the Pulau Pinang rice
      granary by comparing their morphological characteristics to those of commercially
      grown rice in the area. Their morphometric relations were established by
      comparing 17 morphological characteristics of the WR accessions and the
      commercial varieties. A total of 36 WR morphotypes were identified from these 4
      sites based on 17 characteristics, which included grain shattering habit and
      germination rate. The Principal Component Analysis (PCA) showed that 45.88% of
      the variation observed among the WR accessions and commercial varieties were
      within the first 3 axes. PB6, PP2 and SGA5 WR accessions had a higher number of
      tillers and longer panicle lengths, culm heights and leaf lengths compared to the
      commercial rice. The grain sizes of the commercial varieties were slightly
      longer, and the chlorophyll contents at 60-70 days after sowing (DAS) were higher
      than those of the WR accessions. Results from this study are useful for
      predicting potential WR accession growth, which might improve WR management and
      agriculture practices that control WR in the future. 

PMID- 24575198
TI  - Toxicity of Barringtonia racemosa (L.) Kernel Extract on Pomacea canaliculata
      (Ampullariidae).
AB  - A number of tropical plant species have been recognised as molluscicidal plants,
      and Barringtonia racemosa (L.) is one of these. The toxicity effects of B.
      racemosa seed kernel extracts on Pomacea canaliculata were evaluated. The lethal
      concentration at 50% [LC50 (lower-upper limits)] values, in ppm/48 hours, were
      70.71 (41.33-120.97), 94.39 (62.48-142.59), 186.84 (129.21-270.17), and 672.72
      (366.57-1234.53) for the extracts withdrawn using dichloromethane (DCM), methanol
      (MeOH), ethyl acetate (EtOAc), heptane (hp) solvents, respectively at 95%
      confidence interval (C. I.). All analyses were conducted using Trimmed Spearman
      Karber (TSK) program version 1.5. It is assumed that the observed biological
      effects of the extracts may be due to the saponins and flavonoids present in the
      seed. The dichloromethanic and methanolic extracts contain saponin and flavonoid
      substances. Therefore these extracts have shown more potent molluscicidal
      activity towards the tested organism compared to the remaining extracts. This
      observed biological activity suggests a promising role for B. racemosa in the
      control of P. canaliculata. 

PMID- 24575199
TI  - Perspectives on the use of algae as biological indicators for monitoring and
      protecting aquatic environments, with special reference to malaysian freshwater
      ecosystems.
AB  - Algal communities possess many attributes as biological indicators of spatial and
      temporal environmental changes. Algal parameters, especially the community
      structural and functional variables that have been used in biological monitoring
      programs, are highlighted in this document. Biological indicators like algae have
      only recently been included in water quality assessments in some areas of
      Malaysia. The use of algal parameters in identifying various types of water
      degradation is essential and complementary to other environmental indicators. 

PMID- 24575200
TI  - Distribution of the Sunda Colugo (Galeopterus variegatus) in Malaysia
      (Peninsular, Sabah, Sarawak).
AB  - There is not much information available on the distribution of the Sunda colugo
      (Galeopterus variegates) in Malaysia, despite it being one of only two known
      species in the order Dermoptera. Data on the presence of the Sunda colugo and the
      vernacular names used by various ethnic groups throughout Malaysia were collected
      and compiled from various primary and secondary sources. There were 27 locations
      from Peninsular, 11 locations from Sabah and 34 locations from Sarawak that
      reported the presence of the Sunda colugo throughout Malaysia. The various ethnic
      groups of Malaysia adopted 37 different vernacular names to describe the Sunda
      colugo. This baseline data can be useful for the management authorities in
      conducting periodic monitoring and will enhance our knowledge of the population
      dynamics of the Sunda colugo in Malaysia. 

PMID- 24575201
TI  - Studies on homalomeneae (araceae) of borneo v: a new species and new supergroup
      record, of homalomena from sabah, malaysian borneo.
AB  - Homalomena galbana Baharuddin S. & P.C. Boyce is described from the Maliau Basin
      Conservation Area, Sabah, representing the first species of the Homalomena
      Supergroup to be recorded from Sabah, and the first mesophytic species of the
      Supergroup to be described from Borneo. The species is illustrated and a brief
      discussion on the pollination role of interpistillar staminodes is presented. 

PMID- 24575202
TI  - Effects of tocotrienol supplementation on hair growth in human volunteers.
AB  - Studies have shown an association between oxidative stress and alopecia. Patients
      with alopecia generally exhibit lower levels of antioxidants in their scalp area
      as well as a higher lipid peroxidation index. Tocotrienols belong to the vitamin
      E family and are known to be potent antioxidants. Hence, a study was conducted to
      investigate the effect of tocotrienol supplementation on hair growth in
      volunteers suffering from hair loss. Twenty one volunteers were randomly assigned
      to orally receive 100 mg of mixed tocotrienols daily while 17 volunteers were
      assigned to receive placebo capsule orally. The volunteers were monitored for the
      number of hairs in a pre-determined scalp area as well as the weight of 20
      strands of 1 cm length hair clippings at 0 (before supplementation), 4 and 8
      months. The number of hairs of the volunteers in the tocotrienol supplementation
      group increased significantly as compared to the placebo group, with the former
      recording a 34.5% increase at the end of the 8-month supplementation as compared
      to a 0.1% decrease for the latter. Nevertheless, the cumulative weight of 20
      strands of hair clippings did not differ much from the baseline for both
      supplementation groups at the end of the study period. In conclusion, this trial
      demonstrated that supplementation with tocotrienol capsules increases hair number
      in volunteers suffering from hair loss as compared to the placebo group. This
      observed effect was most likely to be due to the antioxidant activity of
      tocotrienols that helped to reduce lipid peroxidation and oxidative stress in the
      scalp, which are reported to be associated with alopecia. 

PMID- 24575203
TI  - Catharanthus roseus Aqueous Extract is Cytotoxic to Jurkat Leukaemic T-cells but
      Induces the Proliferation of Normal Peripheral Blood Mononuclear Cells.
AB  - Research on natural products has been widely used as a strategy to discover new
      drugs with potential for applications in complementary medicines because they
      have fewer side effects than conventional drugs. The aim of the present study was
      to evaluate the in vitro cytotoxic effects of crude aqueous Catharanthus roseus
      extract on Jurkat cells and normal peripheral blood mononuclear cells (PBMCs).
      The aqueous extract was standardised to vinblastine by high performance liquid
      chromatography (HPLC) and was used to determine cytotoxicity by the MTS [3-(4,5
      dimethylthiazol-2-yl)-5(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium]
      assay. DNA fragmentation assay was employed to determine if cell death was due to
      apoptosis. The results showed that the aqueous extract induced cell death of
      Jurkat cells at 24, 48 and 72 hours post-treatment in a time- and dose-dependent
      manner. However, cells treated at 48 and 72 hours produced higher cytotoxic
      effects with half maximal inhibitory concentration (IC50) values of 2.55 MUg/ml
      and 2.38 MUg/ml, respectively. In contrast, the extract induced normal PBMC
      proliferation, especially after 24 hours treatment with 1000 MUg/ml. This result
      indicates that the C. roseus crude aqueous extract showed differential effects of
      inhibiting the proliferation of the Jurkat cell line and promoting the growth of
      PBMCs. These data suggest that the extract may be applicable for modulating the
      normal and transformed immune cells in leukaemia patients. 

PMID- 24575204
TI  - Enhancers of Agrobacterium-mediated Transformation of Tibouchina semidecandra
      Selected on the Basis of GFP Expression.
AB  - Genetic engineering is a powerful tool for the improvement of plant traits.
      Despite reported successes in the plant kingdom, this technology has barely
      scratched the surface of the Melastomataceae family. Limited studies have led to
      some optimisation of parameters known to affect the transformation efficiency of
      these plants. The major finding of this study was to optimise the presence of
      selected enhancers [e.g., monosaccharides (D-glucose, D-galactose and D
      fructose), tyrosine, aluminium chloride (AICI3) and ascorbic acid] to improve the
      transformation efficiency of Tibouchina semidecandra. Agrobacterium tumefaciens
      strain LBA4404 harbouring the disarmed plasmid pCAMBIA1304 was used to transform
      shoots and nodes of T. semidecandra. Different concentrations of the
      transformation enhancers were tested by using green fluorescent protein (GFP) as
      a reporter. The results obtained were based on the percentage of GFP expression,
      which was observed 14 days post-transformation. A combination of 120 MUM
      galactose and 100 MUM tyrosine supplemented with 600 MUM AICI3 in the presence of
      15 mg/l ascorbic acid gave the highest percentage of positive transformants for
      T. semidecandra shoots. Whereas 60 MUM galactose and 50 MUM tyrosine with 200 MUM
      AICI3 in the presence of 15 mg/l ascorbic acid was optimum for T. semidecandra
      nodes. The presence of the hygromycin phosphotransferase II (hptII) transgene in
      the genomic DNA of putative T. semidecandra transformants was verified by PCR
      amplification with specific primers. 

PMID- 24575205
TI  - Recovery of Green Plantlets from Albino Shoot Primordia Derived from Anther
      Culture of Indica Rice (Oryza sativa L.).
AB  - A simple method was developed to permit albino plant regeneration from anther
      culture of Hobigonj Boro (Hbj B) IV and Hbj B VI, two local varieties of aromatic
      indica rice from Bangladesh. Three crucial factors were identified for the albino
      shoot primordia to change into green plantlets in culture; components of M10
      induction medium, callus size (range 0.2-0.4 cm long) and height of shoot
      primordia (range 2-3 mm). Immediate transfer of shoot primordia (2-3 mm) from M10
      medium to regeneration medium followed by continuous incubation under fluorescent
      light (100-lux, 25+/-1 degrees C) triggered albino shoot primordia to turn green
      in 2-3 days. Callus size did not show any effect on the change. Albino plantlets
      derived from anther callus cultured in KA, KB, KC, KD and KE media did not
      recover in both the varieties. Transfer of albino shoot primordia shorter or
      longer than 2-3 mm from the above 5 cultures to regeneration medium did not cause
      the shoot primordia to turn green. 100% albino shoot primordia initiated from Hbj
      B VI and 79% from Hbj B IV in M10 medium changed to green plantlets upon transfer
      to regeneration medium. Subsequent culture and subculture of green plantlets
      showed rapid formation of many new green plantlets. 

PMID- 24575206
TI  - An annotated checklist of the herpetofauna of beris valley, kedah, malaysia.
AB  - The herpetofauna of Beris Valley, Kedah, Malaysia, was studied using a rapid
      assessment survey during a scientific expedition organised by the School of
      Biological Sciences at the Universiti Sains Malaysia, from 14-17 August 2009. All
      amphibians and reptiles were observed and captured during the four-day survey
      along the ditches, roads, dam areas, swamps, forest trails and streams. The
      results showed that 14 species of amphibians from 9 genera and 5 families inhabit
      the area, and 7 species of lizards, 5 species of snakes and 2 species of
      freshwater turtles were also present in the area. Fejervarya limnocharis and
      Microhyla butleri seemed to be the most common amphibians, while Hemidactylus
      frenatus and Varanus salvator were the most common reptiles in the area. This
      report constitutes a preliminary checklist and first record of amphibians and
      reptiles in Beris Valley, Kedah. The number of specimens was less than expected
      because of the very short survey period, but we hope to record more species in
      future studies. 

PMID- 24575207
TI  - Life Table and Population Parameters of Nilaparvata lugens Stal. (Homoptera:
      Delphacidae) on Rice.
AB  - Survival and fertility characteristics of the brown planthopper (BPH),
      Nilaparvata lugens were assessed in the laboratory and field. Life tables and
      population parameters of the BPH were constructed in an environment with
      unlimited food supply and that was free of natural enemies. The highest mortality
      occurred in the immature stage, especially in the first and second instars. The
      life table analysis showed that the population density of BPH decreased
      gradually. The survival ratio of male to female was 0.512:0.488. The females
      lived for a maximum of 20 days. The trend of oviposition showed a peak at around
      the tenth day of the female life. The highest number of eggs produced per female
      per day was 9.63. The intrinsic rate of increase (rm) in egg production per
      female per day was 0.0677 and the daily finite of increase (lambda) was 1.0688
      females per female per day, with a mean generation time (T) of 34.05 days. The
      net reproductive rate (Ro) of the population was 10.02. The population doubling
      time (DT) was 10.42 days. 

PMID- 24575208
TI  - Current Status of Mimosa pigra L. Infestation in Peninsular Malaysia.
AB  - The status and distribution of Mimosa pigra L., a semi-aquatic invasive species
      in Peninsular Malaysia, were continuously assessed between 2004 and 2007. This
      assessment investigated its population stand density and related weed management
      activities. In total, 106 sites of 6 main habitat types i.e., construction site
      (CS), dam/ reservoir (DM), forest reserve (FR), plantation (PL), river
      bank/waterway (RB) and roadside (RD) were assessed, and 55 sites were recorded
      with M. pigra populations. A CS is the most likely habitat to be infested with M.
      pigra (16 out of 18 assessed sites have this weed), whereas none of the FR
      visited were found to harbour M. pigra. In terms of population stand density, 41
      populations were in the low range of stand density (individual plant of <=5 m(
      2)), compared to only 9 populations in the high range of stand density
      (individual plant of >10 m(-2)). In general, the current impact of M. pigra
      infestation on natural habitats is relatively low, as its distribution is only
      confined to disturbed areas. However, continuous monitoring of this weed species
      is highly recommended, especially in the riparian zone and wetland habitats. 

PMID- 24575209
TI  - Monitoring of Water Quality and Microalgae Species Composition of Penaeus monodon
      Ponds in Pulau Pinang, Malaysia.
AB  - Many reports have revealed that the abundance of microalgae in shrimp ponds vary
      with changes in environmental factors such as light, temperature, pH, salinity
      and nutrient level throughout a shrimp culture period. In this study, shrimp
      cultivation period was divided into three stages (initial = week 0-5, mid = week
      6-10 and final = week 11-15). Physical and chemical parameters throughout the
      cultivation period were studied and species composition of microalgae was
      monitored. Physical parameters were found to fluctuate widely with light
      intensity ranging between 182.23-1278 MUmol photon m(-2)s(-1), temperature
      between 29.56 degrees C -31.59 degrees C, dissolved oxygen (DO) between 4.56-8.21
      mg/l, pH between 7.65-8.49 and salinity between 200/00-300/00. Ammonium (NH4 (+)
      N), nitrite (NO2 (-)-N), nitrate (NO3 (-)-N), and orthophosphate (PO4 (3-)-P)
      concentrations in the pond at all cultivation stages ranged from 0.017 to 0.38
      mg/l, 0.24 to 2.12 mg/l, 0.06 to 0.98 mg/l and 0.16 to 1.93 mg/l respectively.
      Statistical test (ANOVA) showed that there were no significant difference
      (p<0.05) in nutrients concentrations among the cultivation stages. All nutrients
      concentrations however were still in the tolerable level and safe for shrimp
      culture. The chlorophyll a contents were found to range from 5.03+/-2.17 to
      32.61+/-0.35 MUg/l throughout the cultivation period. A total of 19 microalgae
      species were found in the shrimp pond, with diatoms contributing up to 72% of the
      species followed by Chlorophyta (11%) and Cyanophyta (11%). However, weekly
      species abundance varied through the study period. At the initial stage, when
      there were no shrimps in the pond, Anabaena spp. and Oscillatoria spp.
      (Cyanophyta) were the dominant species, followed by Chlorella sp. and Dunaliella
      sp. (Chlorophyta). When shrimps were introduced into the pond, Amphora sp.,
      Navicula sp. Gyrosigma sp. and Nitzschia sp. (diatoms) started to exist. At the
      middle and towards the final stage of the shrimp culture period diatoms were the
      dominant species. The Chlorophyta (Chlorella sp.) domination took place only
      twice, which was at week 2 and 13. The absence of some of the coastal water
      microalgae species in the shrimp pond was most likely due to the fact that they
      could not tolerate the physicochemical factors of harsh environment. In this
      study, Cylindrotheca closterium was regarded as the most tolerant species among
      the microalgae due to its ability to exist for 6 weeks out of the 15 weeks of
      cultivation. 

PMID- 24575210
TI  - Diversity of microfungi in sandy beach soil of teluk aling, pulau pinang.
AB  - A total of 82 isolates of microfungi were isolated from 6 sandy soil samples
      collected from Teluk Aling beach, Pulau Pinang. The soil microfungi were isolated
      by using direct isolation, debris isolation and soil dilution techniques. Based
      on morphological characteristics, seven genera of microfungi were identified
      namely, Fusarium (42%), Aspergillus (24%), Trichoderma (13%), Curvularia (9%),
      Colletotrichum (6%), Helminthosporium (4%) and Penicillium (2%). The most common
      species isolated was Fusarium solani followed by Fusarium semitecum, Aspergillus
      niger, Trichoderma viride, Curvularia clavata, Curvularia lunata,
      Helminthosporium velutinum, Colletotrichum sp. and Penicillium chrysogenum. From
      the present study, it appears that the sandy beach contains a microfungi
      reservoir comprising of a variety of genera which contributes significantly to
      the ecological functioning of a marine ecosystem. 

PMID- 24575211
TI  - The Inhibitory Effect of Grasshopper's Cyperus (Cyperus iria L.) on the Seedling
      Growth of Five Malaysian Rice Varieties.
AB  - Experiments were carried out in the laboratory and greenhouse to determine the
      growth inhibitory effects of Grassohopper's cyperus (Cyperus iria L.) on the
      seedlings of 5 Malaysian rice varieties namely MR211, MRQ74, MR220, MR84 and
      MR232. Three concentrations of the aqueous extract of the weed (12.5, 25.0 and
      50.0 g/l) and weed debris (5, 10 and 20 g dry debris/1000 g soil) were used to
      test the allelopathic effect of C. iria on the growth of the rice plants. The
      weed leaf, stem and root extracts reduced the growth of the rice seedlings and
      showed selective activity in the varieties. The C. iria leaf and stem extracts
      showed comparatively higher growth inhibitory effects than those from the root.
      The weed extract caused more reduction in the root length of the rice plant
      compared to the shoot length. Among the rice varieties tested, MR232 was found to
      be more susceptible to the weed inhibitory effect. The leaf extract of C. iria at
      full strength caused root and shoot reduction of MR232 by 88.1% and 73.1%
      respectively (compared to the control). In most cases the fresh weight of the
      rice seedlings were more affected than the plant height. Weed debris caused
      significant reduction of leaf chlorophyll content in all the rice varieties
      tested with the exception of MR211. The chlorophyll content of MR232 was greatly
      affected by the weed debris which caused reduction of 36.4% compared to the
      control. The inhibitory effects of weed extracts and debris on rice growth
      parameters were found to be concentration dependent. 

PMID- 24575212
TI  - A Comparison between Hippurate Hydrolysis and Multiplex PCR for Differentiating
      Campylobacter coli and Campylobacter jejuni.
AB  - Species identification is important for epidemiological, clinical and treatment
      purposes. The aim of this study was to find out whether hippurate hydrolysis is a
      reliable test for differentiating between Campylobacter coli and Campylobacter
      jejuni. To achieve this, hippurate hydrolysis test was compared with multiplex
      Polymerase Chain Reaction (mPCR) for their ability to speciate C. coli and C.
      jejuni. Eighteen Campylobacter strains from poultry samples were used for this
      study. The results from 17 of the 18 strains were in agreement with both methods.
      Thus, the hippurate hydrolysis test can be used for distinguishing C. jejuni from
      C. coli although occasionally some strains of C. jejuni may be mis-identified as
      C. coli. 

PMID- 24575213
TI  - Association of Commercial Rice Varieties with Weedy Rice Accessions (Oryza sativa
      complex) in Pulau Pinang's Rice Granary Area.
AB  - Weedy rice (WR) is the most significant weed in direct-seeded fields. It has
      morphological characteristics similar to those of cultivated rice varieties. WR
      is more difficult to control than other weeds. We collected WR accessions from
      four sites within the Pulau Pinang rice growing areas. Thirty six different
      accessions were collected from each site: B, the northern site; P, the central
      site; A, the southern site; and N, the southwestern site. Wild rice (Oryza
      rufipogon), which grows in the sampled areas, was also collected together with
      four varieties (MR84, MR185, MR211 and MR219) that have been widely planted in
      these areas for a long period of time. The objective of this study was to compare
      the morphological characteristics of the WR accessions and cultivated rice.
      Twenty characteristics were observed for the comparison of WR accessions and rice
      cultivars. Morpho-matrix analyses allowed the specimens to be grouped to two main
      groups (A and B), based on a 95% dissimilarity matrix. Group A was subdivided
      into 7 subgroups consisting of a few WR accessions, wild rice and MR211
      (control), and group B was subdivided to 10 subgroups consisting of other WR
      accessions and the 3 other control varieties. Dendrogram analysis indicated that
      the morphological traits used in this study were able to differentiate among the
      WR accessions and the cultivars, except for rice cultivar MR211 and WRA8, which
      grouped together in subgroup A2. STRUCTURE program analysis indicated that all
      individuals were distinguishable and were divided into 18 clusters. These results
      suggest that some genes of the WR accessions have been influenced by commercial
      varieties. The information gained from this study will be useful to develop rice
      weed management protocols and good agricultural practices to control WR in the
      future. 

PMID- 24575214
TI  - Diversity Pattern of Bats at Two Contrasting Habitat Types along Kerian River,
      Perak, Malaysia.
AB  - We present an assessment of the diversity of Malaysian bats at two contrasting
      habitat types (secondary forest and oil palm plantation) along the Kerian River
      surveyed between February 2009 and February 2010. Three hundred and twenty nine
      individual bats from 13 species representing 4 families were recorded using 10
      mist nets. The most commonly caught bat in the secondary forest was Cynopterus
      brachyotis (n=75), followed by Macroglossus minimus (n=10). Meanwhile, in the oil
      palm plantation, the most commonly caught bat was Cynopterus brachyotis (n=109),
      followed by Cynopterus horsfieldi (n=76). The netting efforts were equal for both
      habitat types. The total sampling nights for each habitat type was 5460. The oil
      palm plantation had a greater bat abundance that was significantly different from
      that of the secondary forest, with 209 and 120 individuals, respectively (Mann
      Whitney U-test = 31.5, p<0.05). Our results suggest that there is no significant
      difference in species richness between the two sites. However, the invasion by
      disturbance-associated species of the secondary forest is indicative of negative
      effects on the forest and animal diversity in this area. Forest managers should
      consider multiple measures of forest fragmentation sensitivity before making any
      forest management decisions. 

PMID- 24575216
TI  - Effects of Environmental Factors on Growth and Artemisinin Content of Artemisia
      annua L.
AB  - Seeds of two selected clones of Artemisia annua L., TC1 and TC2, were germinated
      in a greenhouse. Four-week-old seedlings from both clones were grown in the Thu
      Duc province of Ho Chi Minh City on 2(nd) January 2009 and Da Lat on 20(th)
      January 2009. During this study period in Thu Duc province, which is situated 4-5
      m above sea level, was experiencing a tropical, dry season with temperatures
      ranging from 26.2 degrees C-32.8 degrees C. Da Lat, situated at 1500-2000 m above
      sea level, was having temperate, dry season with lower temperatures, ranging from
      10.5 degrees C-18.0 degrees C. The high temperatures and low elevation in Thu Duc
      Province led to slow vegetative growth for all of the plants from the two
      different clones and the artemisinin contents were significantly reduced. The
      temperate environment of Da Lat supported robustly growing plants, with plant
      heights and branch lengths 4-5 times taller and longer that those planted at Thu
      Duc Province. The artemisinin contents of A. annua planted at Da Lat were 3-4
      times greater than those cultivated at Thu Duc Province. Hence, this study
      indicated that the variations observed in plant growth and artemisinin contents
      were due to temperature effects because the two selected clones were genetically
      homogenous. The cold weather of Da Lat was suitable for planting of A. annua as
      opposed to the tropical weather of Thu Duc Province. 

PMID- 24575215
TI  - Genotoxicity Assessment of Water Samples from the Sungai Dua River in Pulau
      Pinang, Malaysia, Using the Allium cepa Test.
AB  - Unwanted side effects from a polluted water body may not be limited to the flora
      and fauna, they may also be transferred to the organisms along the food chain.
      Four water samples collected immediately and five days after rainfall from two
      locations inside the polluted Sungai Dua River (SGD) were tested for toxicity
      using the Allium cepa assay. The samples were analysed for metal content and were
      both macroscopically and microscopically evaluated. The water samples contained
      more sodium (Na(+)) and calcium (Ca(2+)) than the control tap water, and they
      showed root growth and mitotic inhibitions (MI) in A. cepa. However, the
      inhibitory effects were not dose-dependent. No chromosomal aberration (CA) was
      induced at 100.00% (undiluted water sample). These results suggest the water
      samples from SGD had weak mitodepressive and genotoxic effects on the A. cepa
      cells. 

PMID- 24575217
TI  - Avian diversity and feeding guilds in a secondary forest, an oil palm plantation
      and a paddy field in riparian areas of the kerian river basin, perak, malaysia.
AB  - The diversity and the feeding guilds of birds in three different habitats
      (secondary forest, oil palm plantation and paddy field) were investigated in
      riparian areas of the Kerian River Basin (KRB), Perak, Malaysia. Point-count
      observation and mist-netting methods were used to determine bird diversity and
      abundance. A total of 132 species of birds from 46 families were recorded in the
      3 habitats. Species diversity, measured by Shannon's diversity index, was 3.561,
      3.183 and 1.042 in the secondary forest, the paddy field and the oil palm
      plantation, respectively. The vegetation diversity and the habitat structure were
      important determinants of the number of bird species occurring in an area. The
      relative abundance of the insectivore, insectivore-frugivore and frugivore guilds
      was greater in the forest than in the monoculture plantation. In contrast, the
      relative abundance of the carnivore, granivore and omnivore guilds was higher in
      the plantation. The results of the study show that the conversion of forest to
      either oil palm plantation or paddy fields produced a decline in bird diversity
      and changes in the distribution of bird feeding guilds. 

PMID- 24575218
TI  - Bird species diversity in the padawan limestone area, sarawak.
AB  - Bird surveys were conducted in the Padawan Limestone Area for seven days at each
      of two study sites, Giam and Danu, from August to December 2008. The purpose of
      the study was to compare the area's bird species richness and abundance of bird
      species in other limestone areas and in other forest types. The study also
      compared the species richness and relative abundance of birds in undisturbed and
      disturbed areas at both study sites. Twenty mist nets were deployed for 12 hours
      daily. During this study period, direct observations of birds were also made. In
      all, 80 species from 34 families were recorded at both sites. At Giam, 120 birds
      were mist-netted. These birds represented 31 species from 16 families. The direct
      observations at Giam recorded 13 species from 11 families. In the undisturbed
      area, 21 species from 13 families were mist-netted, whereas in the disturbed
      area, 21 species from 10 families were mist-netted. In Danu, a total of 48 birds,
      representing 25 species from 12 families, were mist-netted. The observations at
      Danu recorded 34 species from 19 families. Twelve species from 7 families were
      mist-netted in the undisturbed area, whereas 18 species from 11 families were
      mist-netted in the disturbed area. Statistical analysis showed that the species
      diversity index differed significantly between undisturbed and disturbed areas. 

PMID- 24575219
TI  - The Population Size of the Lesser Bandicoot (Bandicota bengalensis) in Three
      Markets in Penang, Malaysia.
AB  - A study of the population size of Bandicota bengalensis rats in three markets in
      Penang was conducted from April 2004 through May 2005. Taman Tun Sardon Market
      (TTS), Batu Lanchang Market (BTLG) and Bayan Lepas Market (BYNLP) were surveyed.
      Six sampling sessions were conducted in each market for four consecutive nights
      per session. The total captures of B. bengalensis in TTS, BTLG and BYNLP were
      92%, 73% and 89% respectively. The total population of B. bengalensis in TTS was
      estimated as 265.4 (with a 95% confidence interval of 180.9-424.2). The total
      population at BTLG was estimated as 69.9 (with a 95% confidence interval of 35.5
      148.9). At BYNLP, the total population was estimated as 134.7 (with a 95%
      confidence interval of 77.8-278.4). In general, adult male rats were captured
      most frequently at each site (55.19%), followed by adult females (31.69%),
      juvenile males (9.84%) and juvenile females (3.27%). The results showed that the
      number of rats captured at each site differed significantly according to sex
      ratio and maturity (chi(2) = 121.45, df = 3, p<0.01). Our results suggest that
      the population sizes found by the study may not represent the actual population
      size in each market owing to the low numbers of rats recaptured. This finding
      might have resulted from the variety of foods available in the markets. 

PMID- 24575220
TI  - Mating populations of fusarium section liseola from rice, sugarcane and maize.
AB  - Mating studies were conducted on 78 isolates of Fusarium species section Liseola
      from rice, sugarcane and maize. From the crosses with tester strains of
      Gibberella fujikuroi species complex, 64.1% (50 out of 78 isolates) were cross
      fertile with tester strains of mating populations A to E. The results of the
      mating studies showed that of the 50 isolates, 19 belonged to mating population A
      (Gibberella moniliformis), 18 to mating population B (Gibberella sacchari), 4 to
      mating population E (Gibberella subglutinans), 6 to mating population D
      (Gibberella intermedia) and 3 to mating population C (G. fujikuroi).
      Identification of several mating populations from rice, sugarcane and maize could
      be important biological entities under field conditions. 

PMID- 24575221
TI  - The influence of habitat structure on bird species composition in lowland
      malaysian rain forests.
AB  - Bird surveys were conducted in the Bukit Kepala Gajah limestone area in Lenggong,
      Perak from July 2010 to January 2011. The study area was divided into three
      zones: forest edge, forest intermediate and forest interior. A point-count
      distance sampling method was used in the bird surveys. The study recorded 7789
      detections, representing 100 bird species belonging to 28 families. Pycnonotidae,
      Timaliidae and Nectariniidae were the dominant families overall and showed the
      highest number of observations recorded in the study area whereas Motacillidae
      showed the fewest observations. The bird species were grouped into three feeding
      guilds: insectivores, frugivores and others (omnivores, carnivores, nectarivores
      and granivores). The species richness of insectivorous birds differed
      significantly among the forest zones sampled (Kruskal-Wallis: alpha=0.05,
      H=10.979, d.f.=2, p=0.004), with more insectivorous birds occurring in the forest
      interior. No significant differences were found among the zones in the species
      richness of either the frugivore guild or the composite others guild. 

PMID- 24575222
TI  - A Gate-to-gate Case Study of the Life Cycle Assessment of an Oil Palm Seedling.
AB  - The palm oil industry has played an important role in the economic development of
      Malaysia and has enhanced the economic welfare of its people. To determine the
      environmental impact of the oil palm seedling at the nursery stage, information
      on inputs and outputs need to be assessed. The oil palm nursery is the first link
      in the palm oil supply chain. A gate-to-gate study was carried out whereby the
      system boundary was set to only include the process of the oil palm seedling. The
      starting point was a germinated seed in a small polyethylene bag (6 in * 9 in) in
      which it remained until the seedling was approximately 3 to 4 months old. The
      seedling was then transferred into a larger polyethylene bag (12 in * 15 in),
      where it remained until it was 10-12 months old, when it was planted in the field
      (plantation). The functional unit for this life cycle inventory (LCI) is based on
      the production of one seedling. Generally, within the system boundary, the
      production of an oil palm seedling has only two major environmental impact
      points, the polybags used to grow the seedling and the fungicide
      (dithiocarbamate) used to control pathogenic fungi, as both the polybags and the
      dithiocarbamate are derived from fossil fuel. 

PMID- 24575223
TI  - Influence of Life Diet on the Biology and Demographic Parameters of Agistemus
      olivi Romeih, a Specific Predator of Eriophyid Pest Mites (Acari: Stigmaeidae and
      Eriophyidae).
AB  - The influence of various life diets on the biology and demographic parameters of
      the predatory mite, Agistemus olivi Romeih, was studied under laboratory
      conditions. A. olivi successfully developed and reproduced on all of the tested
      eriophyid mites. Feeding on Aceria mangiferae Sayed enhanced the development of
      A. olivi, resulted in the shortest mean generation time and was the most
      commensurate food for the ovipostion of the predator, as exhibited by the highest
      fecundity and net reproductive rate. Preying on Aculops lycopersici (Massee) gave
      the lowest fecundity and net reproductive rate; therefore, this prey was the
      least suitable for the oviposition of A. olivi. Preying on Aculus fockeui (Nalepa
      et Trouessart) and A. mangiferae produced higher intrinsic rates of increase and
      finite rates of increase for the predator in comparison to A. lycopersici, which
      showed the lowest value. These differences in response to various eriophyid pests
      should be considered for the production of healthy cultures of A. olivi. 

PMID- 24575224
TI  - The distribution of anacardiaceae in teluk bahang forest reserve, pulau pinang.
AB  - To investigate the distribution of Anacardiaceae in Teluk Bahang Permanent Forest
      Reserve (TBPFR) in Pulau Pinang, all trees with a diameter at breast high (DBH)
      >= 5 cm were enumerated in a study site constituting 0.4 ha of the reserve.
      Seventy five individuals of Anacardiaceae (14% of all trees) are recorded. These
      individuals represent 4 genera and 5 species, namely, Mangifera pentandra,
      Mangifera macrocarpa, Gluta elegans, Campnosperma auriculatum and Swintonia
      floribunda. The mean density of Anacardiaceae within the study plots is 7.50+/
      8.14 (mean+/-S.D.) per ha whereas the basal area (BA) calculated is 0.97
      m(2)/0.40 ha. The importance value (IVi) for Anacardiaceae is 81%. The estimated
      total aboveground biomass (TAGB) for Anacardiaceae is 24.24 ton/0.40 ha. A total
      of 333 Anacardiaceae saplings with a DBH < 5 cm are recorded. These saplings have
      been identified as juveniles of the genera Gluta (9.99%), Swintonia (84.90%) and
      Mangifera (5.11%). 

PMID- 24575225
TI  - The species composition of thrips (insecta: thysanoptera) inhabiting mango
      orchards in pulau pinang, malaysia.
AB  - A field study was conducted at two localities on Pulau Pinang, Malaysia, during
      two consecutive mango flowering seasons in 2009 to identify variations in the
      species composition of thrips infesting treated and untreated mango (Mangifera
      indica L.) orchards. The CO2 immobilisation technique and the cutting method were
      used to recover different thrips species from mango panicles and weed host
      plants, respectively. The mango panicles and various weed species within the
      treated orchard were found to harbour four thrips species from the family
      Thripidae. These species were identified as Thrips hawaiiensis (Morgan),
      Scirtothrips dorsalis (Hood), Frankliniella schultzei (Trybom) and Megalurothrips
      usitatus (Bagnall). The weed species Mimosa pudica, Cleome rutidosperma,
      Echinochloa colonum, Borreria laevicaulis, Veronia cinerea and Asystasia
      coromandeliana served as additional hosts to these thrips. Six thrips species
      were found in the untreated orchard. These species included Thrips palmi (Karny),
      Haplothrips sp. (Amyot and Serville) and the four thrips species found in the
      treated orchard. A brief description of the larvae for each genus is provided. 

PMID- 24575226
TI  - The Distribution and Conservation Status of Green Turtles (Chelonia mydas) and
      Olive Ridley Turtles (Lepidochelys olivacea) on Pulau Pinang beaches (Malaysia),
      1995-2009.
AB  - The Green Turtle (Chelonia mydas) and Olive Ridley Turtle (Lepidochelys olivacea)
      are the only sea turtles with recorded landings in the Pulau Pinang coastal area.
      The Green Turtle has been the most abundant and widely distributed sea turtle in
      this area since it was first surveyed in 1995. Statistical analysis by the Pulau
      Pinang Department of Fisheries on the distribution of sea turtles from 2001
      through 2009 has identified Pantai Kerachut and Telok Kampi as the most strongly
      preferred beaches for Green Turtle landings, with records for almost every month
      in every year. Green Turtle tracks and nests have also been found along the coast
      of Pulau Pinang at Batu Ferringhi, Tanjong Bungah, Pantai Medan, Pantai Belanda,
      Telok Kumbar, Gertak Sanggul, Moonlight Beach, Telok Duyung, Telok Aling, Telok
      Bahang and Telok Katapang. The Olive Ridley Turtle is present in smaller numbers;
      landing and nesting have only been recorded on a few beaches. There are no
      previous records of Olive Ridley landings at Pantai Kerachut and Telok Kampi, but
      tracks and nests have been found at Telok Kumbar, Tanjong Bungah, Pantai Medan,
      Telok Duyung and Gertak Sanggul. A Turtle Conservation Centre has been
      established at Pantai Kerachut to protect these species from extinction in Pulau
      Pinang. This paper presents details of the records and distribution of sea
      turtles in Pulau Pinang from 1995 through 2009. 

PMID- 24575227
TI  - Redescription of Chironomus javanus and Chironomus kiiensis (Diptera:
      Chironomidae) Larvae and Adults Collected from a Rice Field in Pulau Pinang,
      Malaysia.
AB  - Chironomus javanus (Kieffer) and Chironomus kiiensis Tokunaga were redescribed
      from materials collected from a rice field in Pulau Pinang, Malaysia. The larvae
      can only be distinguished after careful preparation and examination using a
      compound microscope, but the pupae were not useful to differentiate C. javanus
      from C. kiiensis. The adult specimens showed clear body and wing characteristics
      for rapid and accurate identification. 

PMID- 24575228
TI  - Pathology Associated with White Spot Virus (WSV) Infection in Wild Broodstock of
      Tiger Prawns (Penaeus monodon).
AB  - A total of six wild broodstocks of tiger prawns, Penaeus monodon, were found
      positive for White Spot Virus (WSV) with an IQ2000 detection kit. Using
      histopathology, the intranuclear inclusion of haemocyte due to WSV infection was
      observed in the epithelium cells of the antennal gland, stomach and gills. This
      result confirmed that the wild broodstocks were positive with WSV without showing
      any white spot. Additionally, histopathological examination also revealed an
      accumulation of haemocytes around the hepatopancreatic tubules resulting from
      bacterial infection. Encapsulation and nodule formation, as well as related
      necrosis, were also observed around the hepatopancreatic tubules infected with a
      metazoan parasite. Encysted tylocephalum larval cestodes were observed in the
      hepatopancreas, with haemocytic aggregation being observed around the infected
      tubules. These findings showed some bacterial and parasitic infections which, in
      addition to the viral infection itself, could contribute to the 80% mortality
      rate in wild broodstocks infected with WSV. 

PMID- 24575229
TI  - Diversity of fusarium species from highland areas in malaysia.
AB  - Fusarium is a cosmopolitan and highly diversified genus of saprophytic,
      phytopathogenic and toxigenic fungi. However, the existence and diversity of a
      few species of Fusarium are restricted to a certain area or climatic condition.
      The present study was conducted to determine the occurrence and diversity of
      Fusarium species in tropical highland areas in Malaysia and to compare with those
      in temperate and subtropical regions. A series of sampling was carried out in
      2005 to 2009 at several tropical highland areas in Malaysia that is: Cameron
      Highlands, Fraser Hills and Genting Highlands in Pahang; Penang Hill in Penang;
      Gunung Jerai in Kedah; Kundasang and Kinabalu Park in Sabah; Kubah National Park
      and Begunan Hill in Sarawak. Sampling was done randomly from various hosts and
      substrates. Isolation of Fusarium isolates was done by using
      pentachloronitrobenzene (PCNB) agar and 1449 isolates of Fusarium were
      successfully recovered. Based on morphological characteristics, 20 species of
      Fusarium were identified. The most prevalent species occurring on the highlands
      areas was F. solani (66.1%) followed by F. graminearum (8.5%), F. oxysporum
      (7.8%), F. semitectum (5.7%), F. subglutinans (3.5%) and F. proliferatum (3.4%).
      Other Fusarium species, namely F. avenaceum, F. camptoceras, F. chlamydosporum,
      F. compactum, F. crookwellense, F. culmorum, F. decemcellulare, F. equiseti, F.
      nygamai, F. poae, F. proliferatum, F. sacchari, F. sporotrichioides, F.
      sterilihyphosum and F. verticillioides accounted for 1% recoveries. The present
      study was the first report on the occurrences of Fusarium species on highland
      areas in Malaysia. 

PMID- 24575230
TI  - Comparative Study on Vegetative and Reproductive Development between Weedy Rice
      Morphotypes and Commercial Rice Varieties in Perak, Malaysia.
AB  - This study was conducted to examine the variabilities in the chronology of
      vegetative and reproductive development of weedy rice (Oryza spp.) in comparison
      with commercial varieties. Data at different growth stages of 14 weedy rice
      morphotypes and 4 commercial rice varieties were recorded and analysed. Plant
      height of all weedy rice morphotypes were observed to be significantly higher
      compared to the commercial varieties at every growth stages; increase in height
      was between 10-37 cm for weedy rice morphotype, for every 2 weeks. Initial
      tillering ability at 14 days after planting (DAP) was higher in weedy
      morphotypes, however all the commercial rice varieties produced significantly
      higher number of tillers throughout the rest of the vegetative phases.
      Correlation between plant height and tiller number detected that taller plants
      produce fewer tillers than shorter plants. Higher leaf area index (LAI) of all
      weedy morphotypes except PWR01 at early growth stages indicated the vigorous
      growth of the morphotypes. Weedy rice morphotypes showed a wide range of anthesis
      and maturity duration. Accessions from the same weedy rice morphotypes were more
      heterogeneous in the flowering, anthesis and maturity period than the commercial
      varieties. These traits enables identification of weedy rice morphotypes at their
      different growth stages in the field. 

PMID- 24575233
TI  - The amphibian diversity of bukit jana, taiping, perak.
AB  - The study on the amphibian fauna of Bukit Jana, Taiping, Perak was carried out
      from January 2009 until December 2010 with a total of 12 nights of observation.
      Twenty four species of frogs from 14 genera and 6 families were recorded to
      inhabit the Bukit Jana areas. Seven commensal species were found around human
      habitations near the foothill whereas the others are typical forest frogs found
      mostly near the rivers, streams and forest floor. This is the first amphibian
      checklist of Bukit Jana, Perak and it contributed 22% out of 107 species of frogs
      that are recorded to inhabit Peninsular Malaysia. 

PMID- 24575232
TI  - Regeneration of Transgenic Rice with Bacterial ipt Gene Driven by Senescence
      Specific (SAG12) Promoter by Particle Bombardment.
AB  - Transgenic rice plants were generated using particle bombardment to introduce the
      Agrobacterium cytokinin biosynthesis gene driven by Arabidopsis (Arabidopsis
      thaliana) senescence specific promoter (SAG12) for delaying leaf senescence.
      Using two plasmids we co-transformed one week old embryogenic calli derived from
      mature Japonica rice (Oryza sativa) variety Chin Guang. The selectable marker
      hygromycin phosphotransferase (hph) gene and the reporter gene B-beta
      glucuronidase (uidA), both under the control of cauliflower mosaic virus (CaMV)
      35S promoter were placed on the same co-integrate vector whereas the cytokinin
      biosynthesis gene, isopentenyl transferase (ipt) driven by the SAG12 promoter is
      supplied in another plasmid. A total of 32 transgenic rice plants were
      regenerated of which 27 plants were randomly selected for histochemical beta
      glucuronidase (GUS) assay, PCR and Southern blot analysis. Co-integration
      frequencies of 88% and 69% were obtained for two linked genes (uidA and hph) and
      two unlinked genes (hph and ipt gene) respectively in R0 plants. Southern blot
      analysis confirmed the results of histochemical GUS assay and PCR amplifications.
      A complex integration pattern for all the transgenes including the multiple
      copies integration was predominantly observed. 

PMID- 24575231
TI  - Heavy Metals Uptake by Asian Swamp Eel, Monopterus albus from Paddy Fields of
      Kelantan, Peninsular Malaysia: Preliminary Study.
AB  - Swamp eel, Monopterus albus is one of the common fish in paddy fields, thus it is
      suitable to be a bio-monitor for heavy metals pollution studies in paddy fields.
      This study was conducted to assess heavy metals levels in swamp eels collected
      from paddy fields in Kelantan, Malaysia. The results showed zinc [Zn (86.40 MUg/g
      dry weight)] was the highest accumulated metal in the kidney, liver, bone, gill,
      muscle and skin. Among the selected organs, gill had the highest concentrations
      of lead (Pb), cadmium (Cd) and nickel (Ni) whereas muscle showed the lowest total
      metal accumulation of Zn, Pb, copper (Cu), Cd and Ni. Based on the Malaysian Food
      Regulation, the levels of Zn and Cu in edible parts (muscle and skin) were within
      the safety limits. However, Cd, Pb and Ni exceeded the permissible limits. By
      comparing with the maximum level intake (MLI), Pb, Ni and Cd in edible parts can
      still be consumed. This investigation indicated that M. albus from paddy fields
      of Kelantan are safe for human consumption with little precaution. 

PMID- 24575234
TI  - Length-weight and Length-length Relationship of Longsnouted Catfish, Plicofollis
      argyropleuron (Valenciennes, 1840) in the Northern Part of Peninsular Malaysia.
AB  - Scanty information exists pertaining to the length-weight relationship (LWR) and
      length-length relationship (LLR) parameters of longsnouted catfish, Plicofollis
      argyropleuron in lotic systems throughout the northern part of Peninsular
      Malaysia. It is vital to reveal these biological properties of P. argyropleuron
      in Kuala Muda and Merbok estuary for future management and to increase knowledge
      about this fish stocks. The fish samples were randomly collected in the estuary
      area of Kuala Muda and Merbok, Kedah for 10 months from March 2009 to December
      2009. The values of the exponent b in the LWR equations (W = aL(b) ) were
      approximately 3, indicating an isometric growth with high correlation coefficient
      (r(2)). The value of LLR (r(2)>0.9) indicated that they are highly significant
      and highly correlated. These parameters are essential for evaluating the relative
      condition of fish and species managements as well as their fisheries and stock
      assessment. 

PMID- 24575236
TI  - Flowering and fruiting phenology of tree species in mount papandayan nature
      reserve, west java, indonesia.
AB  - Mount Papandayan Nature Reserve (MPNR) is an area highly rich in biodiversity,
      however deforestation has left a vast area urgently in need of reforestation.
      When reforestation is designed to restore some level of biodiversity, it is
      imperative that native tree species are used for planting. This research aimed to
      provide information on the flowering and fruiting phenology of native trees. Such
      information can be useful to plan seed collection and mass seedling production in
      the nursery. The observations were conducted each month during August 2009-July
      2010 by recording flowering and fruiting trees along two survey track passing
      through the middle of the mixed forest of MPNR. Data gathered were used to
      construct a simple phenology calendar. During the study, there were 155 trees of
      43 species found flowering or fruiting along the survey track. The peak time of
      flowering and fruiting was in July (13 species flowering and 19 species
      fruiting), while the lowest level was in October (1 species flowering and 3
      species fruiting). According to the phenology calendar constructed, March to July
      were considered to be the appropriate time to collect seeds of native trees in
      Mount Papandayan. 

PMID- 24575235
TI  - Effects of N(6)-benzylaminopurine and Indole Acetic Acid on In Vitro Shoot
      Multiplication, Nodule-like Meristem Proliferation and Plant Regeneration of
      Malaysian Bananas (Musa spp.).
AB  - Different concentrations of N(6)-benzylaminopurine (BAP) and indole acetic acid
      (IAA) in Murashige and Skoog based medium were assessed for their effects on
      shoot multiplication, nodule-like meristem proliferation and plant regeneration
      of the Malaysian banana cultivars Pisang Mas, Pisang Nangka, Pisang Berangan and
      Pisang Awak. BAP at 1-14 mg L(-1) with or without 0.2 mg L(-1) IAA, or BAP at 7
      14 mg L(-1) with the same concentration of IAA, was evaluated for shoot
      multiplication from shoot tips and the proliferation of nodule-like meristems
      from scalps, respectively. Plant regeneration from scalps was assessed using 1 mg
      L(-1) BAP and 0.2 mg L(-1) IAA separately, or a combination of these two growth
      regulators. Data on shoot multiplication, the proliferation of nodule-like
      meristems with associated plant regeneration were recorded after 30 days of
      culture. A maximum of 5 shoots per original shoot tip was achieved on medium
      supplemented with BAP at 5 mg L(-1) (Pisang Nangka), 6 mg L(-1) (Pisang Mas and
      Pisang Berangan), or 7 mg L(-1) (Pisang Awak), with 0.2 mg L(-1) IAA. BAP at 11
      mg L(-1) with 0.2 mg L(-1) IAA induced the most highly proliferating nodule-like
      meristems in the four banana cultivars. Plant regeneration from scalps was
      optimum in all cases on medium containing 1 mg L(-1) BAP and 0.2 mg L(-1) IAA.
      This is the first report on the successful induction of highly proliferating
      nodule-like meristems and plant regeneration from scalps of the Malaysian banana
      cultivars Pisang Mas, Pisang Nangka, Pisang Berangan and Pisang Awak. 

PMID- 24575237
TI  - Does weather play an important role in the early nesting activity of colonial
      waterbirds? A case study in putrajaya wetlands, malaysia.
AB  - Environmental factors can play important roles in influencing waterbird
      communities. In particular, weather may have various biological and ecological
      impacts on the breeding activities of waterbirds, though most studies have
      investigated the effect of weather on the late stages of waterbird breeding
      (e.g., hatching rate, chick mortality). Conversely, the present study attempts to
      highlight the influence of weather on the early nesting activities of waterbirds
      by evaluating a recently established mixed-species colony in Putrajaya Wetlands,
      Malaysia. The results show that only rainfall and temperature have a significant
      influence on the species' nesting activities. Rainfall activity is significantly
      correlated with the Grey Heron's rate of establishment (rainfall: rs = 0.558, p =
      0.03, n = 72) whereas both temperature and rainfall are associated with Painted
      Stork's nesting density (temperature: rs = 0.573, p = 0.013; rainfall: rs = 
      0.662, p = 0.03, n = 48). There is a possibility that variations in the rainfall
      and temperature provide a cue for the birds to initiate their nesting.
      Regardless, this paper addresses concerns on the limitations faced in the study
      and suggests long-term studies for confirmation. 

PMID- 24575238
TI  - Induction of an Antibody Response against Plasmodium falciparum F2RIIEBA by
      Heterologous Prime-boost Immunisation.
AB  - Heterologous prime-boost immunisation strategies can evoke powerful antibody
      responses and may be of value in developing an improved malaria vaccine. Herein,
      we show that an immunisation protocol that primes Balb/c mice with a recombinant
      Bacille Calmette-Guerin (rBCG) vaccine consisting of a plasmid encoding a
      synthetic fragment of the ESAT-6 epitope of Mycobacterium tuberculosis, the
      fragment 2 region II of erythrocyte-binding antigen (F2RIIEBA) and the three
      repeat sequences of the circumsporozoite protein (NANP)3 of Plasmodium falciparum
      before subsequently boosting the mice with either two doses of the rBCG clone or
      with a DNA vaccine expressing the native form of F2RIIEBA generating higher serum
      anti-F2RIIEBA antibody levels than an immunisation protocol that calls for a
      homologous prime-boost with two doses of rBCG. These results demonstrate the
      potential of DNA vaccination in boosting the antibody response to a recombinant
      vaccine expressing multiple epitopes. 

PMID- 24575239
TI  - Status of water quality subject to sand mining in the kelantan river, kelantan.
AB  - This paper aimed to describe the effects of sand mining on the Kelantan River
      with respect to physical and chemical parameter analyses. Three replicates of
      water samples were collected from five stations along the Kelantan River
      (November 2010 until February 2011). The physical parameters included water
      temperature, water conductivity, dissolved oxygen (DO), pH, total dissolved
      solids (TDS), total suspended solids (TSS) and turbidity, whereas the chemical
      parameters included the concentration of nitrogen nutrients such as ammonia,
      nitrate and nitrite. The Kelantan River case study revealed that TSS, turbidity
      and nitrate contents exceed the Malaysian Interim National Water Quality Standard
      (INWQS) range and are significantly different between Station 1 (KK) and Station
      3 (TM). Station 1 has the largest variation of TDS, TSS, turbidity and nitrogen
      nutrients because of sand mining and upstream logging activities. The extremely
      high content of TSS and the turbidity have caused poor and stressful conditions
      for the aquatic life in the Kelantan River. 

PMID- 24575240
TI  - A survey of benthic assemblages of foraminifera in tropical coastal waters of
      pulau pinang, malaysia.
AB  - The distribution of benthic Foraminifera throughout the coastal waters of Taman
      Negara Pulau Pinang (Penang National Park), Malaysia was studied to assess the
      impact of various anthropogenic activities, such as fishing, ecotourism and
      floating cage culture. Samples were obtained at 200 m intervals within the
      subtidal zone, extending up to 1200 m offshore at Teluk Bahang, Teluk Aling,
      Teluk Ketapang and Pantai Acheh. The depth within coastal waters ranged between
      1.5 m and 10.0 m, with predominantly muddy substrate at most stations. Water
      quality analysis showed little variation in micronutrient (nitrite, NO2; nitrate,
      NO3; ammonia, NH4 and orthophosphate, PO4) concentrations between sampling
      stations. Temperature (29.6+/-0.48 degrees C), salinity (29.4+/-0.28 ppt),
      dissolved oxygen content (5.4+/-0.95 mg/l) and pH (8.5+/- 0.13) also showed
      little fluctuation between stations. A total of nine genera of foraminifera were
      identified in the study (i.e., Ammonia, Elphidium, Ammobaculites, Bigenerina,
      Quinqueloculina, Reopax, Globigerina, Textularia and Nonion). The distribution of
      benthic foraminifera was dominated by opportunistic groups that have a high
      tolerance to anthropogenic stressors. Ammonia had the highest frequency of
      occurrence (84.7%), followed by Bigenerina (50%), Ammobaculites (44.2%) and
      Elphidium (38.9%). The Ammonia-Elphidium Index (AEI) was used to describe the
      hypoxic condition of benthic communities at all sites. Teluk Bahang had the
      highest AEI value. The foraminiferal assemblages and distribution in Teluk
      Bahang, Teluk Aling, Teluk Ketapang and Pantai Acheh showed no correlation with
      physical or chemical environmental parameters. 

PMID- 24575241
TI  - Antibiogram Profile of Salmonella enterica Serovar Typhi in India - A Two Year
      Study.
AB  - Typhoid fever continues to remain a major health problem in the developing world,
      and the emergence of multidrug-resistant (MDR) strains has further reduced
      therapeutic options for treatment of the disease. The National Salmonella and
      Escherichia Centre in Kasauli, India received 128 Salmonella Typhi isolates
      during 2008-2009. These were evaluated for antimicrobial resistance, prevalent
      resistotypes and the proportion of MDR strains, using standard methods for 11
      antimicrobials. An abrupt decrease in the proportion of MDR strains was observed.
      Only 4.7% of the isolates were found to be MDR with resistotypes chloramphenicol
      ampicillin-streptomycin-nalidixic acid-trimethoprim (C-AS-Na-Tr) and
      chloramphenicol-ampicillin-nalidixic acid-trimethoprim (C-A-Na-Tr), which is very
      low compared to other studies from India. Nalidixic acid resistance was found to
      be present in 93.8% of the isolates. Moreover, the difference in the mean minimum
      inhibitory concentration (MIC) of ciprofloxacin for nalidixic acid-resistant and
      nalidixic acid-sensitive strains was found to be statistically significant
      (p<0.001), which calls into question the further use of ciprofloxacin for the
      treatment of typhoid fever because of potential treatment failures. The low
      proportion of MDR strains increases the possibility of first-line drugs for the
      treatment of typhoid fever. 

PMID- 24575242
TI  - Barium Levels in Soils and Centella asiatica.
AB  - In this study, Centella asiatica and surface soils were collected from 12
      sampling sites in Peninsular Malaysia, and the barium (Ba) concentrations were
      determined. The Ba concentration [MUg/g dry weight (dw)] was 63.72 to 382.01
      MUg/g in soils while in C. asiatica, Ba concentrations ranged from 5.05 to 21.88
      MUg/g for roots, 3.31 to 11.22 MUg/g for leaves and 2.37 to 6.14 MUg/g for stems.
      In C. asiatica, Ba accumulation was found to be the highest in roots followed by
      leaves and stems. The correlation coefficients (r) of Ba between plants and soils
      were found to be significantly positively correlated, with the highest
      correlation being between roots-soils (r=0.922, p<005), followed by leaves-soils
      (r=0.890, p<005) and stems-soils (r=0.848, p<005). This indicates that these
      three parts of C. asiatica are good biomonitors of Ba pollution. For the
      transplantation study, four sites were selected as unpolluted [(Universiti Putra
      Malaysia (UPM)], semi-polluted (Seri Kembangan and Balakong) and polluted sites
      (Juru). Based on the transplantation study under experimental field and
      laboratory conditions, Ba concentrations in C. asiatica were significantly
      (p<0.05) higher after three weeks of exposure at Seri Kembangan, Balakong and
      Juru. Thus, these experimental findings confirm that the leaves, stems and roots
      of C. asiatica can reflect the Ba levels in the soils where this plant is found.
      Three weeks after back transplantation to clean soils, the Ba levels in C.
      asiatica were still higher than the initial Ba level even though Ba elimination
      occurred. In conclusion, the leaves, stems and roots of C. asiatica are good
      biomonitors of Ba pollution. 

PMID- 24575243
TI  - Bacillus licheniformis BT5.9 Isolated from Changar Hot Spring, Malang, Indonesia,
      as a Potential Producer of Thermostable alpha-amylase.
AB  - A total of 34 bacterial isolates were obtained from soil samples collected from
      Changar Hot Spring, Malang, Indonesia. Of these, 13 isolates produced a zone of
      hydrolysis in starch-nutrient agar medium and generated various amylases in
      liquid medium. One isolate was selected as the best amylase producer and was
      identified as Bacillus licheniformis BT5.9. The improvement of culture conditions
      (initial medium pH of 5.0, cultivation temperature of 50 degrees C, agitation
      speed of 100 rpm and inoculum size of 1.7 * 10(9) cells/ml) provided the highest
      amylase production (0.327 U/ml). 

PMID- 24575244
TI  - Isolation of a Pigment-producing Strain of Staphylococcus kloosii from the
      Respiratory Tree of Holothuria (Mertensiothuria) leucospilota () from Malaysian
      Waters.
AB  - Staphylococcus kloosii, an orange pigment-producing bacterium, was isolated from
      the respiratory tree of Holothuria (Mertensiothuria) leucospilota (Brandt 1835)
      from Teluk Nipah, Pangkor Island, Perak, Malaysia. This report is the first
      documentation of this Gram-positive strain, referred to as Strain 68 in Malaysia.
      A partial 16S ribosomal RNA gene sequence of the mesophilic strain has been
      registered with GenBank (National Center for Biotechnology Information, US
      National Library of Medicine) with accession number JX102547. Phylogenetic
      analysis using the neighbour-joining method further supported the identification
      of Strain 68 as S. kloosii. The circular strain produced orange pigments on
      tryptone glucose yeast extract agar (TGYEA) and in nutrient broth (NB) at
      approximately pH 7. The visible spectra of ethanolic and methanolic pigment
      extracts of the bacterial strain were considered identical with lambdamax at 426,
      447 and 475 nm and lambdamax at 426, 445 and 473 nm, respectively. Both visible
      spectra resemble the visible spectra of lutein, which is a commercial carotenoid;
      however, further analyses are required to confirm the identity of this pigment.
      The methanolic extracts of the intracellular pigments comprised at least three
      pigment compounds: an orange pigment compound (major compound), a yellow pigment
      compound (the least polar) and a pink pigment compound (the most polar). These
      findings are the first documentation of the pigment composition of S. kloosii as
      no such record could be found to date. 

PMID- 24575245
TI  - Binary Combination of Carica papaya, Areca catechu and Myristica fragrans with
      Piperonyl Butoxide / MGK-264 against Freshwater Snail Lymnaea acuminata.
AB  - Piperonyl butoxide (PB) and MGK-264 were used to enhance the toxicity of the
      active components papain, arecoline and myristicin from the plants Carica papaya,
      Areca catechu and Myristica fragrans, respectively, against the vector snail
      Lymnaea acuminata. A time- and dose-dependent relationship was observed for the
      toxicity of these combinations. The toxic effects of these plant-derived
      molluscicides in combination with the synergists PB and MGK-264 were several
      times higher than the effect of the individual treatments. The highest degree of
      synergism was observed when MGK-264 was used in combination with C. papaya latex
      (10.47-fold increase) and PB was used with papain (8.35-fold increase). 

PMID- 24575246
TI  - The vertical dynamics of larval chironomids on artificial substrates in lake lido
      (bogor, indonesia).
AB  - The composition and abundance of chironomid larval communities was studied on
      artificial substrates in Lido Lake, located in Bogor, West Java, Indonesia. The
      lake is organically enriched as a result of fish farming activity. Seventy two
      artificial substrates were deployed at three depths (2.0, 3.5 and 5.0 m) at two
      sites: a cage culture site and a non-cage culture site (control). Larval
      chironomid larvae were collected 7, 14, 28 and 56 days after the artificial
      substrates were deployed. In addition, selected physical and chemical parameters
      of the water were simultaneously measured. Three chironomid subfamilies, the
      Chironominae, Tanypodinae and Orthocladiinae, were found at both sites. At the
      cage culture site, both diversity and total abundance were significantly higher
      at the 2.0 and 3.5 m depths than at the 5.0 m depth, but this was not the case at
      the non-cage culture site. Based on pooling of the data from all depths, a Mann
      Whitney U test showed that the non-cage culture site had a significantly higher
      diversity and total abundance than the cage culture site. Dissolved oxygen (DO)
      and turbidity showed significant differences between the 2.0 m depth and the 2
      greater depths at the cage culture site, whereas none of the environmental
      parameters showed significant differences among the three depths at the non-cage
      culture site. A comparison of the environmental parameters at the same depth at
      the two sites showed significant differences in turbidity, pH and DO. A Spearman
      rank correlation analysis at the cage culture site showed that abundance and DO
      were positively correlated, whereas abundance and turbidity were negatively
      correlated. However, only pH was negatively correlated with abundance at the non
      cage culture site. 

PMID- 24575247
TI  - Evaluating Frugivore-fruit Interactions Using Avian Eye Modelling.
AB  - Fruit phenotypes are often hypothesised to be affected by selection by
      frugivores. Here, we tested two hypotheses concerning frugivore-fruit
      interactions from the perspective of fruit colours. We measured the spectral
      properties of 26 fruits and the associated leaves of plants from 2 islands in New
      Zealand. Visual observations were also performed to record the birds that fed on
      the fruits. First, we tested the fruit-foliage hypothesis, where fruit colours
      are assumed to be evolutionarily constrained by their own leaf colour to maximise
      colour contrast and fruit conspicuousness. We ran a null model analysis comparing
      fruit colour contrast using an avian eye model. Second, we tested the frugivore
      specificity hypothesis, where specific fruit colours are thought to be connected
      with a specific bird frugivore. We performed a regression on the number of bird
      visits against the fruit colour in tetrahedral colour space based on an avian eye
      calculation using Mantel's test. The results show that fruit colours are not
      constrained by their own leaf colours. There is also no relationship or pattern
      suggesting a link between a specific fruit colour and specific bird visitors. We
      suggest that although fruit colour is one of the most highly discussed
      components, it is not the most important single deciding factor in frugivore
      fruit selection. 

PMID- 24575248
TI  - The Distribution of Nesting White-bellied Sea-eagle (Haliaeetus leucogaster) in
      Penang National Park, Malaysia: Conservation and Management Issues.
AB  - Taman Negara Pulau Pinang (Penang National Park) is the only site on Pulau Pinang
      that supports a large population of the White-bellied Sea-eagle (WBSE) Haliaeetus
      leucogaster; however, the nesting sites of WBSEs have not been widely studied. As
      information on the location of WBSE nesting sites is very important for
      conservation works by local authorities, the objective of this study was to
      determine the distribution of nesting WBSEs in the coastal dipterocarp forest of
      Penang National Park. Surveys were conducted from December 2007 to July 2008 and
      October 2008 to April 2009, covering the breeding season of the species
      (September-July). The nesting sites were observed by boat along the coastline of
      Penang National Park and by performing ground surveys along the seashore at
      accessible areas; the nest survey was conducted three days/month from 0900 to
      1500. A total of 34 WBSE nesting sites was located. Most of the occupied nests
      (seven nests) were found at Muka Head and Pantai Kerachut areas, which exhibit
      the densest concentration of occupied WBSE habitat in Penang National Park. WBSEs
      preferred to build their nests around Muka Head, which could be due to the
      frequent occurrence of whirlpools in the water body around that area. Aquatic
      animals, such as sea snakes and fish, stunned by the whirlpools would emerge to
      the sea surface, facilitating the foraging and feeding of WBSEs. Our results
      indicate that it is important to maintain and improve areas of suitable nesting
      habitat for WBSEs. Management actions should include (1) the yearly monitoring of
      known breeding sites throughout Penang National Park during the breeding season
      to determine breeding success over time, (2) recognising the critical habitat or
      nest-site selection of WBSEs, (3) establishment of a buffer zone surrounding
      nesting sites and potential habitat from human disturbance, and (4) encouraging
      on-going research to further understand this species. 

PMID- 24575249
TI  - Determination of Phylogenetic and Molecular Characteristics of Three Malaysian
      Ginger Cultivars (Zingiber officinale Roscoe) Using Microsatellite DNA.
AB  - Three Malaysian ginger cultivars (Bukit Tinggi, Tanjung Sepat and Sabah) were
      collected and examined for genetic polymorphisms using microsatellite DNA
      primers. The single microsatellite oligonucleotide primers (CATA)5, (GATA)5 and
      (GAC)6 were used in polymerase chain reactions (PCRs). These PCR reactions
      produced 7 polymorphic bands with an average of 2.334 polymorphic bands per
      primer, leading to an average polymorphism rate of 17.9%. Cluster analysis
      revealed 87.50% similarity between Bukit Tinggi and Tanjung Sepat, 64.27%
      similarity between Bukit Tinggi and Sabah and 56.25% similarity between Tanjung
      Sepat and Sabah. DNA sequencing of the polymorphic PCR products of Tanjung Sepat
      ginger revealed the characteristic features of a putative new gene: a core
      promoter sequence, an enhancer and a transcription start site. Cluster analysis
      using the unweighted pair group method with arithmetic average (UPGMA) was used
      to construct a phylogenetic tree, which indicated that Bukit Tinggi ginger is
      genetically more closely related to Tanjung Sepat ginger than to Sabah ginger.
      Based on the results of this study, we concluded that there is genotypic
      variation among ginger cultivars, and the microsatellite DNA primers described
      here are useful for detecting polymorphic DNA in Malaysian ginger cultivars.
      Additionally, these microsatellite DNA primers may be used as molecular markers
      for discriminating among select Malaysian ginger cultivars. 

PMID- 24575250
TI  - A Case Study on the Mortality of Cobia (Rachycentron canadum) Cultured in
      Traditional Cages.
AB  - The mass mortality of cobia (Rachycentron canadum) within 2-3 days was reported
      by 3 private farms in Bukit Tambun, Pulau Pinang, in February and March 2007.
      Only cobia with body weights of 3-4 kg were affected. Most diseased cobia swam on
      the surface and displayed flashing behaviour. All samples were positive for viral
      nervous necrosis (VNN) with low to medium levels of infection. Infestations by
      leeches (Zeylanicobdella arugamensis), body monogeneans (Benedenia sp.) and
      copepods (Caligus sp.) were also found, but no pathogenic bacteria were isolated.
      All water quality parameters monitored were within optimal ranges for culturing
      cobia. The main causes of high mortality in cobia remain unclear during the
      study. However, we believe that the mass mortality of cobia could be probably due
      to VNN infection and that the rate of mortality will increase further when cobia
      are subjected to aquaculture-related stresses (e.g., limited space). Traditional
      cages with a size of 2 (length) * 2 (width) * 1 m (depth) should only be used for
      rearing cobia below 1 kg in weight given the species' natural behaviours. In
      addition, cobia fingerlings should be screened for VNN prior to stocking them in
      cages. 

PMID- 24575251
TI  - Endophytic Fusarium spp. from Roots of Lawn Grass (Axonopus compressus).
AB  - Fungal endophytes are found inside host plants but do not produce any noticeable
      disease symptoms in their host. In the present study, endophytic Fusarium species
      were isolated from roots of lawn grass (Axonopus compressus). A total of 51
      isolates were recovered from 100 root segments. Two Fusarium species, F.
      oxysporum (53%) and F. solani (47%), were identified based on macroconidia and
      conidiogenous cell morphology. The detection of endophytic F. oxysporum and F.
      solani in the roots of lawn grass contributes to the knowledge of both the
      distribution of the two Fusarium species and the importance of roots as
      endophytic niches for Fusarium species. 

PMID- 24575252
TI  - Termite infestation associated with type of soil in pulau pinang, malaysia
      (isoptera: rhinotermitidae).
AB  - Nine soil samples from nine buildings infested with Coptotermes gestroi in Pulau
      Pinang, Malaysia, were tested for the type of soil texture. The soil texture
      analysis procedures used the hydrometer method. Four of nine buildings (44%)
      yielded loamy sand-type soil, whereas five of nine buildings (56%) contained
      sandy loam-type soil. 

PMID- 24575253
TI  - Assessment of antibody titers and immunity to Hepatitis B in children receiving
      chemotherapy.
AB  - BACKGROUND: There is a decrease in vaccine-specific antibody to certain vaccine
      preventable diseases in children after chemotherapy, but the frequency of non
      immune patients is not clear. In the present case-control study, was taken under
      investigation protection level to Hepatitis B infection in children 6 months
      after completing chemotherapy. MATERIALS AND METHODS: In this study 68 patients
      with cancer and 68 healthy children were enrolled. Patients were 1.5 -12 years
      old with completed standard chemotherapy at least for 6 months. All the patients
      and healthy children were negative for HBsAg and HBeAg and had received Hepatitis
      B vaccination. IgG antibody concentrations against Hepatitis B Virus (HBV) were
      determined in the patients receiving chemotrapy and healthy subjects serum by
      ELISA method. IgG antibody titer > 10 mIU/ml was considered as baseline
      protective titer for preventing HBV infection. RESULTS: Anti-HBs antibody titer
      in 19.12% of patients was less than 10 mIU/ml and 11.76% of the patients had
      borderline antibody titer (10-20 mIU/ml). In healthy subjects, 2.94% and 5.88%
      had antibody titer < 10 mIU/ml and 10-20 mIU/ml, respectively. According to
      statistical analysis, frequency of non immune subjects in children with cancer
      was significantly higher than those in healthy children (P-value=0.024).
      CONCLUSION: HBV vaccination post-intensive chemotherapy in the children with
      cancer is strongly recommended.

PMID- 24575254
TI  - Association and Distribution of Hypertension, Obesity and ABO Blood groups in
      Blood Donors.
AB  - BACKGROUND: Hypertension is a major health problem, especially because it has no
      clear symptoms. It is strongly correlated with modifiable risk factors such as
      adiposities, age, stress, high salt intake. Overweight and obesity is
      conveniently determined from BMI and visceral adiposity is determined by waist
      circumference. ABO blood group is one such factor which needs to be investigated.
      The present study was performed to assess the association and distribution of
      hypertension, obesity, ABO blood groups in different categories of blood donors
      and its multipurpose future utilities for the health planners. MATERIALS AND
      METHODS: A retrospective study was carried out on 23, 320 blood donors during a
      period of one year. All the blood donors were measured BMI, ABO blood group,
      systolic and diastolic blood pressure were determined and correlated for each
      other. RESULTS: Hypertension of ABO blood group was B (8.7%) followed by group O
      (7.6%) group A (3.7%) and group AB (1.9%). In obesity of ABO blood group was B
      (7.9%) followed by group O (6.2%) group A (5.8%) and group AB (1.0%).
      Statistically significant difference was found in both groups (p < 0.001).
      CONCLUSION: The B blood group in blood donor was more susceptible to hypertension
      and obesity.

PMID- 24575255
TI  - Effect of the Garlic Pill in comparison with Plavix on Platelet Aggregation and
      Bleeding Time.
AB  - INTRODUCTION: Platelet aggregation plays a significant role in the etiology of
      cardiovascular diseases. Therefore, treatments to inhibit platelet aggregation
      can reduce the risk of coronary thrombosis. Several studies indicated that garlic
      can inhibit platelet aggregation. This study aimed to determine the effect of
      garlic in comparison with Plavix on platelet aggregation. MATERIALS AND METHODS:
      In this randomized clinical trial, platelet aggregation and bleeding time was
      obtained from 36 healthy volunteers. Volunteers were randomly divided into 4
      groups. The first, second and third groups respectively received 600, 1200 and
      2400 mg garlic and the fourth group received 75 mg Plavix for three weeks.
      Afterwards, platelet aggregation and bleeding time were both evaluated and the
      results before and after the study were compared. Data were analyzed using SPSS
      software version 16. RESULTS: Platelet aggregation induced by adenosine
      diphosphate and arachidonic acid agonists decreased in the groups that used 1200
      or 2400 mg garlic. This difference was statistically significant (p<0.05). As
      compared to the other groups, the bleeding time also increased in those received
      2400 mg garlic pill. CONCLUSION: Since garlic can inhibit platelet aggregation,
      it is suggested to use it as a supplementary treatment to reduce platelet
      aggregation is highly recommended.

PMID- 24575256
TI  - The Benefits of vitamin E on liver function and the hemopoietic System in
      thalassemia Patients.
AB  - BACKGROUND: beta-Thalassemic children have oxidative stress and antioxidant
      deficiency even without iron overload status. In these patients, tissue damage
      due to oxidative stress may be occurred. Also, it seems that thalassemic patients
      have higher levels of ALT, AST therefore, the main aim of the present study was
      to determine the benefits of vitamin E as an antioxidant supplements in beta
      Thalassemia children. MATERIALS AND METHODS: This clinical trial was carried out
      on 45 beta-thalassemic patients undergoing occasional transfusions (24 males, 21
      females), mean age 16+/- 8 years, admitted to Yazd and Shahid Sadoughi hospital
      in 2011. Fallowing three months treatment of vitaminE (vitamin E 400-600
      unit/day),liver function test and hemopoitic system parameters were measured.
      RESULTS: Fourty five patients with laboratory confirmation of beta-Thalassemia
      were recruited following three months vitamin E supplementation, liver function
      test had higher improvement compared to hemopoitic system parameters , and also
      serum SGOT was significantly reduced (P-value<0.004 ). CONCLUSION: It seems clear
      that treatments of beta-thalassemic patients with vitamins E have benefits in
      promoting antioxidant status and may improve liver function test, as AST and ALT
      to decrease but this supplement is not effective for hemopoietic system
      variables.

PMID- 24575257
TI  - Evaluation of Hemoglobin Concentration of Cord, Capillary and Venous sampling in
      Neonates.
AB  - BACKGROUND: Anemia is one of the most common abnormalities in pediatric medicine.
      Considerable differences are seen in the peripheral blood indices of infants in
      developing countries. The aim of this study was to determine and compared blood
      hemoglobin concentration in three sites of sampling in neonate. MATERIALS AND
      METHODS: 1600 term and preterm new infant in three sites of sampling (cord,
      capillary and venous) were taken under investigation. All neonates were examined
      during first day. The methodology excluded patients with a high likelihood of
      receiving blood transfusions and those who had a diagnosis of neonatal anemia.
      Finally, obtained data were analyzed and then compared to other hematology
      results. RESULTS: Mean hemoglobin value obtained from cord was 15.39+/- 5.39 SD
      and from capillary were 19.62+/- 5.75 SD and from venous were 17+/- 7.79 SD. Mean
      hemoglobin value of cord in term neonates were 15.4+/- 5.07 SD and pre term
      neonates were 14.77+/- 1.69 SD. (P=0.036) Mean hemoglobin value of capillary in
      term neonates were 19.63+/- 5.76 SD and pre term neonates were 18.85+/- 1.79 SD.
      (P=0.015) Mean hemoglobin value of venous in term neonates were 17.01+/- 7.81 SD
      and pre term neonates were 16.15+/- 1.76 SD. (P=0.012) There was a correlation
      between cord and capillary mean hemoglobin. (P=0.0235). CONCLUSIONS: The
      capillary samples had a higher mean hemoglobin concentration than other groups.
      There was no difference between these data with respect to the hemoglobin values
      for any groups.

PMID- 24575258
TI  - The role of exon 45 and 16 in the pathogenesis of Von Willebrand disease in
      Iranian Patients.
AB  - BACKGROUND: Von Willebrand disease (VWD) is an autosomal recessive congenital
      bleeding disorder with deficiency or dysfunction of von Willebrand factor (VWF).
      The gene encoding for the VWF is located on chromosome 12, which is 178 Kb with
      52 exons. Various mutations of this gene is responsible for the clinical features
      of VWD, but some single nucleotide polymorphisms make the molecular diagnosis of
      it very complicated.In this study genetic variations in two exons (45 & 16) of
      VWF gene in Iranian patients suffer from type 3 VWD from south west of Iran were
      evaluated. MATERIALS AND METHODS: Genetic variations in exon 45 and exon 16 of
      VWF gene were evaluated in 33 patients diagnosed with type 3 VWD from south west
      of Iran. Two exons with their flanking introns were amplified by PCR and
      amplicons were analyzed by sequencing for any molecular changes. RESULTS: No
      mutation was found in both selected regions. An A/C polymorphism in intron 44 was
      recognized in all patients in homozygous manner. This SNP reported for the first
      time from Iranian VWD patients. CONCLUSION: Mutation of VWF gene is different in
      various ethnic groups, which finding of is important in the diagnosis of the VWD,
      especially for prenatal diagnosis. A few mutations are reported for exon 45 and
      16 of this gene in Iran and other countries. But, present study didn't find any
      mutation in these patients. Mutation in other exons or introns should be
      evaluated in affected individuals from south west of Iran.

PMID- 24575259
TI  - Assessment Hepatomegaly and liver Enzymes in 100 Patients with beta Thalassemia
      Major in Mashhad, Iran.
AB  - BACKGROUND: Frequent blood transfusion in patients with beta thalassemia major
      can lead to iron overload especially in liver. Chronic iron overload could cause
      cirrhosis of the liver. Transfusion- transmitted hepatitis B and C also could
      develop cirrhosis in individuals. MATERIALS AND METHODS: The present cross-
      sectional descriptive study is to assess hepatomegaly and liver enzymes in 100
      patients with beta thalassemia major, ages between 2-18 years old. The study was
      carried out retrospectively. One hundred medical records have chosen from 400
      samples of thalassemia major patients, who are under a regular care of the
      department of sarvar clinic. RESULTS: Out of these patients, 55% were male and
      45% female. The mean age of thalassemia patients was 10.8+/- 4.4 years. The mean
      and S. D of hemoglobin, ferritin, deferoxamine dosage was 8.5 +/- 1.5g/dl , 2183
      +/- 1528 ng , 30 +/- 11.16 mg/kg, respectively. Forty six percent of them had
      hepatomegaly. The mean and S. D of AST and ALT were 95+/- 70 IU/L and 70 +/-35U/L
      respectively. Splenectomy was performed on 44% of patient. CONCLUSION:
      Hepatomegaly is one of the most common findings in the thalassemic patient that
      induced with hemosiderosis and hepatitis.

PMID- 24575260
TI  - Hematologic manifestations in a child with HIV; a Case Report.
AB  - BACKGROUND: Immune deficiency in human might be primary or secondary and could be
      seen with a wide variety of manifestations. In the following, we presented a
      Child with various complains that diagnosed to have HIV infection. CASE REPORT: A
      2/5 y/o child was admitted to the hospital for FUO with prolonged cough, FTT,
      cervical lymphadenopathy, hepatosplenomegaly and bilateral optic neuritis. . He
      was hospitalized for fever, cytopenia and hepatosplenomegaly one year ago, and
      three months later in an outpatient visit, these signs improved, except
      thrombocytopenia. In evaluation, bicytopenia, elevated ESR, hyperlipidemia,
      hyperproteinemia, thrombosis of the transverse sinus of brain, antiphospholipid
      antibodies , decreased levels of protein S and factor V Leiden and increased
      level of anti thrombin III were detected. Consequently, the result of HIV
      antibody showed positive. In addition to warfarin and cotrimoxazole therapy, he
      was referred to special center for possible HARRT therapy. CONCLUSION: In
      approach to patients with various clinical presentations such as cytopenia,
      recurrent or persistent lymphadenopathy, unexplained hyperproteinemia or
      hyperlipidemia, evaluation of HIV infection is highly recommended for
      consideration and further therapy.

PMID- 24575261
TI  - Socioeconomic status and other characteristics in childhood leukemia.
AB  - BACKGROUND: Leukemia is the most prevalent childhood cancer, and Acute
      Lymphoblastic Leukemia (ALL) constitutes 75% of all cases. Some epidemiological
      studies have shown a relationship between socioeconomic status (SES) and some
      childhood cancers. In the present study, an attempt was made to assess
      socioeconomical status in a case-control study. MATERIALS AND METHODS: In 2010, a
      case-control study was conducted on 100 cases of acute lymphoblastic leukemia
      aged 1 to14 years in Department of Pediatric Oncology of Dr.Sheikh Hospital in
      Mashhad - Iran and matched age and sex with 400 healthy controls. Data was
      collected by interview using a questionnaire. Ninety five percent confidence
      intervals were used to measure the relationship between childhood Acute
      Lymphoblastic Leukemia and parental education, income status, father's job
      (Socioeconomic status), number of children, birth score and paternal smoking.
      RESULTS: There was a significant difference in parental education level, income
      status, and number of children, birth score, father's job and paternal smoking
      between two groups. Regression analysis showed that the risk of childhood ALL
      associated with paternal smoking, and father's high risk job. Fifty percent cases
      and thirty five percent of control groups located in upper lower and lower middle
      class of socioeconomic status, respectively. There is a meaningful different
      between socioeconomic status in two groups. But the risk of childhood ALL did not
      associate with socioeconomic status. CONCLUSION: The results suggest that
      paternal smoking and father's high risk job are related to risk of childhood
      leukemia. It should be considered for planning support.

PMID- 24575262
TI  - Effect of two Different Concentrations of Propofol and Ketamine Combinations
      (Ketofol) in Pediatric Patients under Lumbar Puncture or Bone Marrow Aspiration.
AB  - BACKGROUND: Ketamine is an anesthetic drug that is importantly analgesic without
      respiratory depression. Ketamine increases blood pressure and heart rate.
      Propofol is an anesthetic drug with good sedation, rapid recovery, but it causes
      respiratory depression, low heart rate and low blood pressure. Combination of
      Ketamine and Propofol provides sedation, analgesia and rapid recovery with
      hemodynamic stability and minimal respiratory depression. The aim of this study
      was to compare two different combinations of these two drugs to reach necessary
      sedation scale for the Lp or BMA in pediatric with ALL. MATERIALS AND METHODS:
      This randomized, double blinded study was designed to compare the quality of
      sedation and side effects of intravenous Ketofol on 60 patients of both gender.
      Patients received titrated injection of a solution containing combination of one
      part of Ketamine and two parts of Propofol (1:2) (group I) or one part of
      Ketamine and three parts of Propofol (1:3) (group II) to reach almost near 5
      sedation level (using Ramsay Sedation Scale). Respiratory and hemodynamic
      profiles, amount of drug injected and side effects were recorded. RESULTS: These
      drug combinations were used on 60 children with a median age of 6.2 years. In
      this study, recovery time and hallucination was significantly high in group I,
      but in both groups hemodynamic were stable, amnesia was enough, and there was no
      respiratory depression. CONCLUSION: Lower doses of Ketamine in these combinations
      have lower psycho mimetic side effects, and shorter recovery time.

PMID- 24575263
TI  - Evaluation of cardiac function in patients with thalassemia intermedia.
AB  - BACKGROUND: Thalassemia intermedia is a variety of beta thalassemia which shows
      clinical symptoms somewhere between asymptomatic carriers and thalassemia major.
      Cardiac dysfunctions due to chronic anemia and hemosiderosis are the major causes
      of death in these patients. The purpose of this study is to evaluate cardiac
      function in these patients by echocardiography. MATERIALS AND METHODS: This case
      control study was conducted on 22 thalassemic patients (mean: 16.5+/-5.8 years)
      and 66 healthy individuals (mean:16.07+/- 2.9years) as a control group from
      January 2007 to July 2008. There was no sign of cardiac involvement by physical
      examination, chest x-ray and ECG in patients. Echocardiographic parameters were
      measured in groups, and finally data was analyzed by SPSS software. RESULTS: The
      mean of left ventricular myocardial performance index (MPI) (P-value=0.0001) and
      left ventricular mass index (LVMI) (P-value=0.0001) have statistically
      significant difference. Mean of interventricular septal dimension in diastole
      (IVSD), left ventricular posterior wall thickness in diastole (LVPWD),
      interventricular septal dimension in systole (IVSS) and left ventricular
      posterior wall dimension in systole (LVPWS) were also statistically significant
      with a P-value of, 0.002, 0.001, 0.01, 0.003, respectively. Aortic Pre-ejection
      period/Ejection time (PEP/ET) (P-value=0.009), ejection fraction (EF) (P
      value=0.019), fractional shortening (SF) (P-value=0.041), left ventricular
      isovolumetric contraction time (ICT) (P-value=0.0001) and left ventricular
      isovolumetric relaxation time (IRT) (P-value=0.0001) were statistically
      significant. Mean of right ventricular MPI (P-value=0.0001) and IRT (P
      value=0.0001) were also significantly different between two groups. Others
      echocardiographic parameters were not statistically significant (P-value>0.05).
      CONCLUSION: Heart failures are earlier affected thalassemia intermedia patients
      compared with control group.

PMID- 24575264
TI  - Iron deficiency and iron deficiency anemia in children with febrile seizure.
AB  - BACKGROUND: Febrile seizure (FS) is the most common childhood seizures which
      occur in 2-5% of children. Studies about association between iron deficiency and
      febrile seizure have shown contradictory results. The purpose of this study was
      to compare the iron status of children with first febrile seizure and healthy
      control group. MATERIALS AND METHODS: In an analytic case-control study , iron
      status of 6 to 60 months old admitted children with first FS to Shahid Sadoughi
      Hospital from December 2011 to August 2012 was evaluated and compared with
      healthy age and sex matched control children whom were referred for routine
      health care to primary health care center of Azadshar Yazd, Iran. RESULTS: Forty
      five (44%) girls and 55 boys with a mean age of 23.7 +/- 14.3 months were
      evaluated. In children with FS , hemoglobin level (11.46 +/- 1.18 g/dl vs. 11.9
      +/- 0.89 g/dl, p= 0.042) , serum iron levels (48.91 +/- 22.96 MUg/dl vs. 75.13 +/
      35.57 MUg/dl , p= 0.001) and serum ferritin level (38.52 +/- 11.38 ng/ml vs.
      54.32 +/- 13.46 ng/ml, p= 0.001) were lower than in healthy children group . Iron
      deficiency (48% vs. 28% , odds ratio 4.3, p=0.03) and iron deficiency anemia (22%
      vs. 10% , odds ratio = 3.16, p= 0.04) were more frequent in children with FS.
      CONCLUSION: Based on the result of this study, iron deficiency could be an
      important risk factor for development of febrile convulsion. Evaluation of iron
      status is encouraged to be performed in children with febrile seizure.

PMID- 24575266
TI  - Premarital Screening of Beta Thalassemia Minor in north-east of Iran.
AB  - BACKGROUND: Beta thalassemia is a preventable disease. Iran has about
      20,000Patients who are homozygote for beta-thalassaemia and 3,750,000 carriers.
      The aim of this study was to determine the prevalence of beta thalassemia minor
      among men who underwent premarital screening in Quchana city in Khorasan Razavi
      region of Iran. MATERIALS AND METHODS: This research is a descriptive cross
      sectional study. From 2010 to 2011, all participants (1000) under marriage coming
      to health center of Quchan underwent routine mandatory tests. Participants were
      considered to have beta-thalassemia minor on the condition that hey had a mean
      corpuscular volume (MCV) <80fl and a mean corpuscular hemoglobin (MCH) <27 pg and
      a hemoglobin A2 level >3.5%. Venous blood was taken into an EDTA tube and the
      complete blood count and red blood cell indices were measured with a Coulter
      automated cell counter. Electrophoresis was performed on cellulose acetate.
      RESULTS: Mean and SD of hemoglobin, MCV and MCH were 16+/-2.9, 91+/-4 and 28.4+/
      2, respectively. Hemoglobin A2 Higher than 3.5 percent was reported as 3.5%.The
      prevalence of beta-thassemia minor with high hemoglobin A2 and microcytic
      hypochromic anemia was 3.5% (P-value). CONCLUSION: In countries with high
      prevalence of hemoglobinopathies, a premarital screening program is helpful for
      identification and prevention of high-risk marriages. Detecting carrier couples
      with premarital screening program is an effective way of controlling thalassemia
      major.

PMID- 24575265
TI  - Thrombocytopenia and Associated Factors in Neonates Admitted to NICU during Years
      2010_2011.
AB  - BACKGROUND: Thrombocytopenia is the most common hematological abnormality which
      is encountered in the neonatal intensive care unit (NICU). The incidence in
      neonates varies greatly, depending upon the population studies. According to the
      frequency of thrombocytopenia and its complications and because of lack of such
      research in Iran, this study was performed on neonates admitted to Shahid Sadughi
      NICU during years 2011-2012. MATERIALS AND METHODS: In a retrospective study, 350
      neonates who were admitted to NICU were enrolled in the study. They were
      categorized to three groups regarding platelet count: mild, moderate and severe
      thrombocytopenia. Incidence of thrombocytopenia was determined and contribution
      of variables such as sex, gestational age, intrauterine growth retardation,
      asphyxia, sepsis, necrotizing enterocolitis, blood group, placental insufficiency
      in Gestational Diabetes Mellitus (GDM) and hypertension (HTN) were analyzed.
      RESULTS: Neonatal thrombocytopenia was found in 100(28.5%) of 350 subjects,
      consisted of 75.3% early onset and 24.7% late onset, which most of them (96.5%)
      had mild and moderate thrombocytopenia, and just 3.5% had developed severe
      thrombocytopenia. Thrombocytopenia was associated with sepsis, intrauterine
      growth retardation sepsis, asphyxia, GDM, maternal hypertension and prematurity.
      There was no relation between occurrence of thrombocytopenia and gender.
      CONCLUSION:  The incidence of neonatal thrombocytopenia was 28.5 %. Significant
      maternal risk factors that lead to thrombocytopenia were HTN and preeclampsia,
      while risk factors of neonates were asphyxia, sepsis and Intera Uterus Growth
      Retardation.

PMID- 24575267
TI  - Crude Extract from Ziziphus Jujuba Fruits, a Weapon against Pediatric Infectious
      Disease.
AB  - BACKGROUND: Pediatric infectious disease is one of the main problems in cancerous
      children that treat by chemotherapy drugs. Thus, study in this regard is
      necessary. The aim of this study was to evaluate antimicrobial properties of
      ethanolic extract of Ziziphus Jujuba fruits against different infectious
      pathogens. MATERIALS AND METHODS: This study is descriptive. In vitro
      antimicrobial activity of extract was assessed on gram negative and gram positive
      bacteria as well as fungi. The antimicrobial activity was tested by Radial
      Diffusion Assay (RDA) and Minimal Inhibitory Concentration (MIC) methods.
      RESULTS: The results showed a wide antimicrobial activity of the extract against
      the microbes studied. Escherichia coli was the most susceptible to the extracts
      among tested microorganisms for which the MIC was 0.65+/-0.22 mg/ml. Amongst the
      bacterial strains investigated, Staphylococcus aureus was the most resistant
      strain with MIC of 2.26+/-0.68 mg/ml. The ethanolic extract also showed
      antimicrobial activity on the fungi studied as no growth was observed in 2.35+/
      0.38 and 2.86+/-0.7 mg/ml concentration for Candida albicans and Aspergillus
      fumigatus, respectively. The results of qualitive and quantitative test are well
      indicative of the extract effective activity against the microbes mentioned.
      CONCLUSION: Confirming the potential antimicrobial activities of crude extract of
      Ziziphus Jujuba fruits, this study suggested that ethanolic extracts of this
      plant is appropriate candidate for treatment of microbial infections, especially
      pediatric infectious diseases.

PMID- 24575269
TI  - Investigation of the Effect of Folic Acid Based Iron Oxide Nanoparticles on Human
      Leukemic CCRF-CEM Cell Line.
AB  - BACKGROUND: Nanoparticulate drug delivery systems have attracted significant
      attention in the field of cancer nanotechnology. This study determines the effect
      of folate-based Fe2O3 nanoparticles. This study aimed to decorate nanoparticles
      with folate (FA), a molecular ligand for 'active' targeting of cancerous cells
      and the application of modified-nanoparticles in cancer treatment. MATERIALS AND
      METHODS: The nanoparticles were prepared by a solvent evaporation and
      emulsification cross-linking method and anticancer activity of agent was
      evaluated on CCRF CEM cells, derived from human blood cancer samples. RESULTS:
      The physicochemical properties of the nanoparticles were characterized by various
      techniques, and uniform nanoparticles with an average particle size of 110+/-15
      nm were obtained. Cytotoxicity tests showed that the SPIO-FA had higher cell
      toxicity, and confocal microscopy analysis confirmed excellent cellular uptake
      efficiency. CONCLUSION: These results indicate that FA based SPIO-NPs have
      potential uses as anticancer drug carriers and also have an enhanced anticancer
      effect.

PMID- 24575268
TI  - Homozygous delta-beta Thalassemia in a Child: a Rare Cause of Elevated Fetal
      Hemoglobin.
AB  - BACKGROUND: Delta beta (deltabeta) thalassemia is an unusual variant of
      thalassemia with elevated level of fetal hemoglobin (HbF). Homozygous patients of
      this disorder, unlike beta-thalassemia, show mild anemia. Only few cases of
      deltabeta-thalassemia have been reported from India in the available indexed
      English literature. CASE PRESENTATION: A four-year old male child was evaluated
      for recent-onset jaundice. Hematological investigations showed mild anemia with
      microcytic hypochromic red cells. A comprehensive analysis of hemoglobin by high
      performance liquid chromatography (HPLC) showed complete absence of HbA and HbA2
      with HbF constituting 100% of the hemoglobin. Hemoglobin analysis of both parents
      showed elevated level of HbF with normal HbA2. A final diagnosis of deltabeta
      thalassemia in the child with both parents being carriers was rendered.
      CONCLUSION: Delta beta-thalassemia is an uncommon cause of markedly elevated
      fetal hemoglobin beyond fetal period. Clinical and haematological parameters
      should be evaluated to render an accurate diagnosis.

PMID- 24575270
TI  - General anesthesia for lumbar puncture and bone marrow aspiration /biopsy in
      children with cancer.
AB  - BACKGROUND: Multiple procedures (Lumbar puncture and bone marrow aspiration
      /biopsy) cause pain, stress, depression and etc for the patients and their
      families. Various methods have been recommended for pain reduction during
      invasive procedures. The aim of this study is to report the complications
      following general anesthesia. MATERIALS AND METHODS: In this prospective
      observational study, two hundred and two children with cancer were enrolled. All
      patients received propofol 2.5 mg /kg and fentanyl 1 ug/kg. After adequate
      anesthesia, procedures were performed by a pediatric oncologist. All anesthesia
      complications were classified into two groups: Intraoperative and Postoperative
      complications. Complications which were recorded include: abnormal age-specific
      bradycardia (<=20 * baseline), decrease in arterial oxygen saturation (<=90%),
      laryngospasm, vomiting, agitation, headache, hypothermia (<35 C degrees ),
      hyperthermia (>37/8 C degrees ), signs of allergy, traumatic LP (bloody), and
      unusual local bleeding. RESULTS: In this study, 118 males and 84 females
      underwent 623 general anesthetic procedures with a median of 3 procedures per
      patient. Intraoperative period complications occurred in 48 of total 623
      procedures (7.7 %). The most common complications were traumatic LP, bradycardia
      and decrease in arterial oxygen saturation which occurred in 25, 6 and 6 cases,
      respectively. Postoperative period complications occurred in 74 (11.9%) cases.
      The most common complications were vomiting, agitation and headache, decrease O2
      saturation and bradycardia. CONCLUSION: General anesthesia by propofol and
      fentanyl may be a good choice for short-term painful procedures in children
      undergoing treatment for bone marrow aspiration/biopsy and intratechal injection.

PMID- 24575271
TI  - A study of leptin serum concentrations in patients with major Beta-thalassemia.
AB  - BACKGROUND: The aim of this study was to evaluate leptin serum levels in patients
      with major beta thalassemia which was also associated with their ferritin serum
      levels. MATERIALS AND METHODS: This case-control study was performed on 90
      children -6 months to 16 years old, in Zabol, Amir- al- Momenin Hospital.
      Patients were divided in two groups and were matched in age and sex. All Children
      were examined and those eligible children who had not known heart disease, iron
      deficiency anemia, kidney disease, diabetes, fever and systemic diseases were
      enrolled after taking the informed consent of their parents. After collecting the
      samples, leptin and ferritin levels of the serum were measured in two groups by
      ELISA method. Then, the data was analyzed by the related statistical tests and
      SPSS 20 software. RESULTS: The mean of the serum levels of leptin and ferritin
      showed a significant difference in the case and control groups (P-value<0.05). An
      inverse statistical correlation was found for the serum levels of leptin and
      ferritin among the studied groups (P-value<0.05). Levels of leptin in the case
      group showed a significant gender difference (P-value<0.05), while based on BMI
      and age, no significant difference was observed for the serum levels of leptin in
      the case group. CONCLUSION: Based on the results of this study, major thalassemia
      reduces serum levels of leptin regardless of age and body mass. The study also
      found an inverse statistical correlation between serum levels of leptin and
      ferritin among the studied people.

PMID- 24575272
TI  - The effect of granulocyte colony stimulating factor administration on preterm
      infant with neutropenia and clinical sepsis: a randomized clinical trial.
AB  - BACKGROUND: This study was conducted to evaluate the clinical effect of
      Granulocyte Colony Stimulating Factor (GCSF) on prognosis of neonatal sepsis.
      MATERIALS AND METHODS: Present study is a double- blinded randomized clinical
      trial, conducted on 46 preterm infants with neutropenia (Absolute Neutrophil
      Count (ANC) <= 5000 / MUL) and clinical sepsis. Infants were randomly allocated
      into two groups. In the first group (treatment group), infants were treated with
      GCSF for up to 5 consecutive days with 10 MUg/ kg in addition to standard
      treatment protocols, and in other group, infants received normal saline as the
      placebo. Each infant was monitored for 14 days. Primary outcome was mortality
      during 14 days after entering the study, and secondary outcome was the incidence
      of positive blood culture, weight gain on the fourteenth day, the duration of
      hospitalization and medication side effects. RESULTS: In the treated group, only
      one death was observed (P-value=1.00). However, no positive results for cultures
      were reported. Only one case in the treatment group and 3 patients in the control
      group showed feeding intolerance and needed respiratory support (P-value= 0.608).
      Length of hospitalization was 25 +/- 6 days for the treatment group and 30 +/- 7
      days for the control group which was statistically significant (P-value=0.042).
      CONCLUSION: The results of this study demonstrated that GCSF could reduce the
      hospital stay, but no significant effect was observed on mortality rate,
      respiratory or feeding status.

PMID- 24575273
TI  - G6PD Enzyme Deficiency in Neonatal Pathologic Hyperbilirubinemia in Yazd.
AB  - BACKGROUND: About 7.5% of the world population carries one or two deficient copy
      of glucose-6-phosphate dehydrogenase (G6PD) genes. According to WHO, its
      prevalence in Iran is 10 to 14.9%. This study aimed on determination of frequency
      of G6PD deficiency in neonates with jaundice who were hospitalized during 6
      months (September 2008 to February 2009) in the city of Yazd, Iran. MATERIALS AND
      METHODS: In this study, 105 icteric neonates in the hospitals of Yazd were
      evaluated. Data was collected from hospital records, and the G6PD activity was
      measured by photometric biochemical assay. Statistical analysis of data was
      performed by the SPSS-16 software, using Student's t-test and Pearson's chi
      squared test. RESULTS: Between all of studied neonates, 19 (18.1%) had G6PD
      deficiency, and consisted of 15 boys (29.4% of boys) and 4 girls (7.4% of girls).
      In 100% of cases, the jaundice began in the first week after birth. The average
      total serum bilirubin at hospitalization was 17.22 mg/dL. In 31.5% of the G6PD
      defficient neonates, exchange transfusion became necessary, which is
      significantly more than the rate in G6PD-sufficient (4.6%) neonates (P
      value<0.05). CONCLUSION: In general, the frequency of G6PD deficiency in this
      study seems quite high. Regarding its severity and frequent need for exchange
      transfusion, we recommend that all of the icteric neonates should be evaluated
      for G6PD activity. Also, it is better to test for G6PD deficiency in all of the
      neonates, to detect its presence and to prevent its complications such as favism
      and oxidant drug-induced hemolysis, since the test has a low cost.

PMID- 24575274
TI  - Effect of thyroid dysfunctions on blood cell count and red blood cell indice.
AB  - BACKGROUND: Thyroid hormones have a crucial role in metabolism and proliferation
      of blood cells. Thyroid dysfunction induces different effects on blood cells such
      as anemia, erythrocytosis leukopenia, thrombocytopenia, and in rare cases causes'
      pancytopenia. It also alter RBC indices include MCV, MCH, MCHC and RDW. Thus this
      study attempted to evaluate effect of hypo & hyperthyroidism on blood cell count
      and RBC indices. MATERIALS AND METHODS: This study performed on 102 patients with
      hypothyroid (14.1 years), 84 with hyperthyroid (15.6 years) and 118 healthy
      individuals (15.2 years) as control group. Initially patients TSH level of
      patients was determined by ELISA method, and then according to TSH ranges (0.3
      5.5uIU/mL) patients were divided into two Hyperthyroidism (TSH<0.3uIU/mL) and
      hypothyroidism (TSH>5.5uIU/mL) groups. Then, complete blood count was measured by
      cell counter. Finally, obtained results were analyzed by SPSS software. RESULTS:
      Analyzes of obtained data revealed statistically significant difference between
      two groups of patients in RBC count, MCH, MCHC, RDW, HB and HCT(P-value<0.05),
      but the difference was not significant for WBC and PLT counts and MCV (P
      value>0.05). CONCLUSION: In case of patients with unknown hematological
      dysfunctions, must be evaluated for thyroid hormones.

PMID- 24575275
TI  - Antibiotic Resistance Patterns of Escherichia coli Isolated from Children in
      Shahid Sadoughi Hospital of Yazd.
AB  - BACKGROUND: Growth of drug resistance is related to number of microbial
      characteristics, selective pressure by antibiotic use and social and technical
      vicissitudes that enhance the transmission of antibiotic resistant organisms. The
      aim of this study was to investigate antimicrobial-resistance of Escherichia coli
      isolated from children in Shahid Sadoughi hospital of Yazd. MATERIALS AND
      METHODS: In this cross-sectional study, antimicrobial susceptibility to cefixime
      , cefotaxime , ceftazidime , ceftriaxone, ciprofloxacin, gentamicin, imipenem,
      cotrimoxazole and nalidixic acid was determined for 148 E. coli isolates obtained
      from patients less than 18 years of age (hospitalized and outpatient) in Shahid
      Sadoughi hospital of Yazd. RESULTS: Ciprofloxacin was the most active
      antibacterial agent (78% susceptible), followed by gentamicin. High rates of
      resistance were observed for cefixime (57.9%) and cotrimoxazole. The results for
      ceftriaxone, cefotaxime, ceftazidime, ciprofloxacin, gentamicin, imipenem,
      cotrimoxazole and nalidixic acid were insignificant with P-value= 0.302, P-value=
      0.550, P-value= 0.334, P-value= 0.084, P-value= 0.948, P-value= 0.686, P-value=
      0.120 and P-value= 0.162, respectively. The results were significant for cefixime
      with P-value= 0.013. CONCLUSION: The investigation of antimicrobial
      susceptibility is essential, and will help to identify E. coli resistance to
      antimicrobial agents. It also helps to limit E. coli spread.

PMID- 24575276
TI  - Primary follicular lymphoma of the conjunctiva in a 12 year-old male.
AB  - BACKGROUND: Follicular lymphoma (FL) is the second most common adnexal lymphoma
      of the eye that almost all of them are reported in elderly patients. Primary FL
      of the eye has been reported in only two children. Pediatric FL appears to be
      biologically distinct from typical adult FL. In cases without other organ
      involvement excision alone with close monitoring is a treatment of choiceand the
      prognosis is excellent. CASE PRESENTATION: A 12 year -old male with a nodular
      lesion involving the inner can thus of the right eye was admitted to
      ophthalmology clinic. The lesion was painless and the nodule size gradually
      increased over a period of 6 months.Excisional biopsy demonstrated follicular
      lymphoma composed of neoplastic lymphoid cells which arranged in follicular
      pattern without germinal centers. Neoplastic cells were positive for Bcl2 and
      CD20. CONCLUSION: Although follicular lymphoma of the conjunctiva is rare in
      childhood but it could be considered as one of the differential diagnosis in this
      age group.

PMID- 24575277
TI  - Comparing Electrolytes in Prestorage Leukocyte-Reduced Packed Cell versus
      Unfiltered Packed Cell.
AB  - BACKGROUND: Blood transfusion is associated with side effects caused by residual
      leukocytes in blood and blood components. Using leukodepleted blood components
      can decrease some of these adverse effects. Among the various methods to remove
      leukocytes in blood components, prestorage leukoreduction has been most
      efficient, but the evidence of clinical side effects awaits further studies. We
      evaluated changes of electrolytes in prestorage leukocyte-reduced red blood
      cells. MATERIALS AND METHODS: In this case-control study, one hundred twenty
      eight packed cells were studied: 64 unfiltered packed cells and 64 prestorage
      filtered packed cell. Two groups were matched as sex and age. Electrolytes such
      as Calcium, Sodium, and Potassium of two groups were measured, and compared
      during preparation. RESULTS: In this study, mean of Calcium in unfiltered and
      filtered group were 6.16+/-1.09 mg/dl and 5.57+/-2.21 mg/dl, respectively (P
      value<0.055). Mean of Sodium in unfiltered group also was 155.91+/-9.51meq/l and
      in filtered group, 153.05+/-13.21meq/l (P-value<0.163), and mean of Potassium in
      unfiltered group was 5.01+/-1.72 meq/l and in filtered group, 7.42+/-2.45meq/l (P
      value<0.001). CONCLUSION: Releasing of Potassium during preparation of prestorage
      leukoreduction can cause increased Potassium level and hemoglobin concentration
      changes in prestorage filtered packed cell.

PMID- 24575278
TI  - Five-Year Status of Malaria (a Disease Causing Anemia) in Yazd, 2008-2012.
AB  - BACKGROUND: Yazd province which is the host of local and foreign immigrants may
      be faced with contacting malaria. Plasmodium falciparum malaria remains a major
      cause of mortality throughout in the tropical regions of the world.
      Pthophysiologic mechanisms of anemia in malaria is such as direct invasion of Red
      cells, anemia of chronic disease hypersplenism, Hemophagocytic syndrome and
      erythrophagocytosis, dyserythropoirsis, immune haemolysis and cytokine
      deregulation anemia of chronic disorder is characterized by moderate to mild
      normocytic, normochromic anemia along with microcytic hypochromic cells. Malaria
      occurs predominantly in children in the first three years of life. The purpose of
      this study was Demographic study of malaria during 2008 to 2012 in Yazd.
      MATERIALS AND METHODS: This study was an analytic-descriptive and manner
      descriptive study. All episodes (Imported Malaria) of disease from 2008 to 2012
      which were documented in Yazd Central Health Service were carefully studied and
      reported. RESULTS: A total of 206 confirmed reported malaria patients from 2008
      to 2012 were studied; Plasmodium (P). vivax species was mostly, 187(90.78%) and
      Plasmodium (P). Malaria species was Lesley, 1(0.49%). The mean age groups,
      accommodation with local malaria and years of reported outbreaks of different
      strains of the parasite conducted by Fisher exact Test, showed no significant
      difference(P-value>0.05), but the mean of foreigner immigrants of outbreaks of
      different strains of the parasite conducted by Fisher exact Test, showed
      significant difference (P-value= 0.01). CONCLUSION: Although malaria has been
      designed on elimination program in Iran, but in the province of Yazd is reported
      imported malaria and its importance in causing anemia and other blood disorders
      is not negligible.

PMID- 24575279
TI  - Methylene blue based device for pathogen reduction in human plasma.
AB  - BACKGROUND: Despite improvement in safety of plasma transfusion some virus
      transmission still remains a problem. So as World Health Organization (WHO)
      recommends, many countries developed Pathogen Reduction Technologies (PRT) to
      inactivate pathogens, in plasma components. The Methylene Blue (MB) based methods
      is one of the most universal one. The purpose of this research was, produce a
      device that can inactivate viruses in MB environment. MATERIALS AND METHODS: In
      this interventional study, each Plasma Sample was illuminated by 70Pieces (PCs)
      of 1 w red Light Emitting Diodes (LEDs) from one side. These LEDs emit light at
      central wavelength of 627 nm with 20 nm Full Width at Half Maximum (FWHM). Two
      model viruses Herpes Simplex Virus (HSV) and Vesicular Stomatitis Virus (VSV)
      were used and Tissue Culture 50% Infection Dose (TCID50) was used to calculate
      virus Log reduction. Two concentration of MB and 5 different illumination times
      were used. RESULTS: In 10 um concentration of MB, HSV had 6.00+/-0.2 maximum log
      reduction that obtain after 60 minutes illumination and VSV had 5.50+/- 0.3
      maximum log reduction after 75 minutes illumination. In 1 uM concentration of MB,
      HSV had 5.20+/-0.3 maximum log reduction that obtain after 60 minutes
      illumination and VSV had 4.90+/- 0.2 maximum log reduction after 75 minutes
      illumination. CONCLUSION: Results of virus inactivation in this method were
      similar to other methods (P-value<0.05 in comparison with Spring method, and P
      value>0.05 in comparison with Theraflex), and it showed this device could
      inactivate viruses according to WHO recommendation.

PMID- 24575281
TI  - Quality of life in children with beta-thalassemia major at center for special
      diseases.
AB  - BACKGROUND: Knowledge of factors associated with quality of life in patients with
      thalassemia is necessary for creating appropriate clinical programs, social
      support, and improving treatment outcomes. The purpose of this study was to
      determine quality of life in children with thalassemia major at Center for
      Special Diseases of valiasr hospital in Birjand. MATERIALS AND METHODS: This
      cross-sectional descriptive-analytical study was conducted on 40 children over 7
      years of age with thalassemia major. Tools for data collection included a
      demographic questionnaire and World Health Organization Quality of Life
      questionnaire (WHOQOL- Bref) standard questionnaire comprising 26 items to
      determine quality of life in patients with thalassemia. Data was analyzed using
      descriptive statistical tests (mean, SD, and frequency), and inferential
      statistical test (t-test) in SPSS software. RESULTS: Results showed mean score of
      70.37+/-9.88 for quality of life, 25+/-3.06 for physical health, 18.12+/-3.22 for
      mental health, 21.3+/-4.43 for living environment, and 5.95+/-1.58 for
      sociability. There was no significant correlation between quality of life and
      demographic variables. Correlation between social relationships and education
      level was significant (P-value<0.0001).  CONCLUSION: According to the results,
      quality of life of the patient was above average in three dimensions of physical
      health, psychological health, and environmental health, and in order to improve
      quality of life in these children, appropriate programs should be implemented to
      support them physically, mentally and socially, and improve patient's
      relationship with Center for Special Diseases.  

PMID- 24575280
TI  - Comparing the efficacy of ceftazidime and meropenem in treatment of febrile
      neutropenia in pediatric patients with cancer.
AB  - BACKGROUND: In cancer patients, various infections were developed due to severe
      neutropenia resulted from chemotherapy. Ceftazidime is commonly used as
      monotherapy of cancer patients with fever and neutropenia. Meropenem is a new
      carbapenem with more extended antibacterial spectrum including anaerobes. It
      provides better coverage against gram positives. This trial compared the efficacy
      and safety of meropenem with ceftazidime as empirical monotherapy for febrile
      neutropenia in pediatric patients with cancer. MATERIALS AND METHODS: A
      prospective, double-blind, randomized clinical trial was conducted at Departments
      of Pediatric Haematology/Oncology, University Hospitals, Yazd, Iran, during the
      years 2012 to 2013. A total of 48 cancer patients participated in the trial.
      RESULT: In this study, 26 patients (54.16%) were treated by ceftazidime and 22
      patients (45.84%) by meropenem. Mean duration of fever in those who responded to
      treatment in ceftazidime group was 19.43+/-31.04 hours, and in meropenem group
      was 16.53+/-28.77 hours (P-value = 0.965). CONCLUSION: Finding of this study
      indicate that ceftazidime and meropenem have similar efficacy in treatment of
      fever and sever neutropenia. Due to more availability and lower cost of
      ceftazidime than meropenem, ceftazidime is suggested as a first line treatment in
      fever and neutropenia.

PMID- 24575282
TI  - Radiography finding in the jaws in children taking bisphosphonate.
AB  - BACKGROUND: Bisphosphonates inhibit osteoclasts, prevent bone resorption and
      decrease bone turnover. This study examined radiography finding in bisphosphonate
      associated osteonecrosis of jaws. MATERIALS AND METHODS: This is a retrospective
      series of 12 clinically diagnosed patients between 7 to 21 year old (average 13
      years). They required emergency dental conditions requiring management by
      dentist: non healing extraction sockets and pain of bone exposure. The panoramic
      radiography and cone beam computed tomography was performed to assess the
      problem. Thickening of the lamina dura was observed in 7 patients (58.3 %). But
      full-thickness sclerosis was seen in 6 patients (50 %). Sclerotic changes in the
      mandibular canal were noted in 3 patients (25 %). 5 patients (41.6 %) had poorly
      healing or non-healing of socket in extracted tooth and periapical lucencies. 4
      people (33.3 %) had widening of periodontal ligament (PDL) space and osteolysis.
      Sequestra were seen in 3 persons (25 %). Finally in 2 children (16.6 %) were
      found oroantral fistula. Only one child (8.3 %) had thickening of soft tissue mid
      periosteal reaction. RESULTS: Most patients had some degree of osteosclerosis,
      especially in the area of alveolar bone. Thickening of the lamina dura was also
      seen in children. Other findings include: osteolysis, sequestra, periosteal new
      bone formation, widening of PDL,soft tissue thickening, non healing extraction
      sockets, oroantral fistula and periapical lucencies (P-value < 0.05). CONCLUSION:
      Common radiographic features in patients taking bisphosphonate, was
      osteosclerosis. This sclerosis had different views that thickening of the lamina
      dura and alveolar crest were most common.

PMID- 24575283
TI  - Seven Years Trends in Prevalence of Transfusion-Transmissible Viral Infections in
      Yazd blood Transfusion Organization.
AB  - BACKGROUND: Increasing blood supply safety is one of the most important goals of
      blood services in the world. In this study, we reviewed the prevalence rate and
      the trends of three main infections in whole blood donations and strategies for
      improving blood safety in Yazd blood transfusion center, Iran. MATERIALS AND
      METHODS: In this cross sectional study, data on hepatitis B, C and HIV infection
      were extracted from Iranian Donor Database of blood donation from 2004 to 2010 in
      Yazd province. All donors with positive confirmatory test were included. The data
      was analyzed by SPSS software due to demographic factors. RESULTS: The prevalence
      rate of hepatitis B, C and HIV infection decreased during these years (From
      0.37%, 0.14% and 0 percent in 2004 to 0.14%, 0.05% and 0 in 2010, respectively).
      Both hepatitis B and C infections were significantly more in first-time blood
      donors with BSc or BA educational level. The prevalence rate of hepatitis B was
      significantly higher in donors with less than 20 year-old and female donors. The
      prevalence rate of hepatitis C was higherin30-39 age group (P-value= 0.014).
      CONCLUSION: The results showed that the strategies used for improving blood
      safety were efficient. Increasing public knowledge on blood-borne infections and
      their routes of transmission, importance of donating blood only by healthy donors
      are necessary to have a safe blood supply in future.

PMID- 24575285
TI  - Infantile fibrosarcoma in a child: a case report.
AB  - BACKGROUND: Infantile Fibrosarcoma is a rare soft tissue tumor in infants and
      children mostly located in extremities. An infantile and adult form has similar
      histopathological patterns but survival prognosis is much better in infantile
      form. Recurrence of infantile fibrosarcoma is common but the rates of metastasis
      are less than 10 percent in children younger than five Years and 50 percent in
      children more than 10 years old. CASE PRESENTATION: In this case report, we
      presented a nine years girl with a relapsing mass in her left hand. The
      pathologic findings showed sheets of spindle-shaped cells with suggested diagnose
      of infantile fibrosarcoma. She was successfully treated with combination of
      surgery and chemotherapy with a good outcome. CONCLUSION: Infantile fibrosarcoma
      is a differential diagnose of soft tissue mass in infants and children. It has a
      good prognosis and distant metastasis is uncommon. Choice of treatment is surgery
      but chemotherapy and radiotherapy were useful in decrease metastasis.

PMID- 24575284
TI  - Rituximab is Indispensable for Pediatric Heart Transplant Recipients Developing
      Post Transplant Lymphoproliferative Disorders.
AB  - Rituximab, an anti-CD20 agent, has been suggested as an effective strategy to
      deal with post transplant lymphoproliferative disorders (PTLD). In the current
      study, we aim to evaluate the efficacy of rituximab therapy in heart transplant
      population developing PTLD. A comprehensive search of the literature was
      performed to gather the available data on lymphoproliferative disorders occurring
      in heart transplant patients. Finally, data of 125 patients from 26 previously
      published studies were included into the study. Patients who underwent rituximab
      therapy had significantly worse tumoral histopathology features (P-value= 0.003).
      Survival analyses showed no significant difference regarding receiving rituximab
      therapy for heart recipients; however, when the analysis was repeated only
      including data of pediatric patients, significant beneficial effects for
      pediatric were found for rituximab therapy. In fact, no children undergoing
      rituximab therapy died during the follow up. In conclusion, this study showed
      that rituximab therapy in pediatric heart transplant recipients with PTLD
      represents surprisingly excellent results, making rituximab an indispensable
      agent in the management of the disease. To define feasibility of rituximab
      therapy in adult recipients of heart graft with PTLD, randomized controlled
      trials are needed. 

PMID- 24575286
TI  - Evaluation of neuropathy during intensive vincristine chemotherapy for non
      Hodgkin's lymphoma and Acute Lymphoblastic Leukemia.
AB  - BACK GROUND: Vincristine (VCR), is a chemotherapy drug, useful in the treatment
      of leukemia, lymphoma and solid tumor and it is a potent neurotoxin and sensory
      neuropathy drug which a common behavioral toxicity of this drug. Neuropathy is
      common squeal of intensive chemotherapy protocols that contain vincristine and
      corticosteroids. MATERIALS AND METHODS: This study was a retrospective and
      descriptive study of neuropathy during in chemotherapy program with vincristine
      for patients with non-Hodgkin's lymphoma (NHL) and Acute Lymphoblastic Leukemia
      (ALL). Data was analyzed by spss Version16 software. RESULTS: From total of 51
      cases, 23 patients had vincristine neuropathy (45%). Patients with visceral
      neuropathy have shown ileus, constipation in 13 patients (25%), occasionally
      severe diarrhea 11 (21%), mild diarrhea 7 (13.7%) and transient diarrhea in 16
      patients (31%). Motor neuropathy were found in one patient with Bell, s palsy
      (1.9%) and one patient with Hoarseness. 12 patients (23.5%) had some type of
      complication together with sensory peripheral neuropathy. CONCLUSION: Almost half
      of patients with vincristin chemotherapy had neuropathy and the mean age of
      patients with neuropathy was 12.3 years.

PMID- 24575287
TI  - Frequency of iron deficiency anemia in girls studying in mashhad high schools.
AB  - BACKGROUND: Iron deficiency is one of the most prevalent anemia. 2 million people
      in the world suffer from it. All young girls are at higher risk for iron defiency
      anemia, therefore,diagnosis and prevention of this anemia in the young age is
      very important. MATERIALS AND METHODS: A total of 1500 high school girls educated
      in five regions of education of Mashhad (ages 14-18 years) were studied. Cell
      blood count (CBC), serum iron, total iron binding capacity(TIBC),ferritin and
      peripheral blood smear were performed . If mean corpuscular volume (MCV) was less
      than normal(<76fl) and Red blood cell (RBC) was more than normal(>5*106/mm3 ),
      hemoglobin electrophoresis was subjected to test by methods of cellulose acetate
      to check the possibility of thalassemia minor.The data was analyzed by
      SPSS(version19) and Minitab software. RESULT: This is a descriptive cross
      sectional research. From 1500 under-experiment people,1094 cases (72.9%) were non
      infected, 310 cases(20.7%) had iron deficiency anemia, and 96 cases(6.4%) had
      other disorders such as thalassemia. In girls with anemia, 272 cases (87.7%) were
      in stage I, 17 cases (5.5%) in stage II and 21 cases (6.8%) in stage III. The
      average age in stage I was higher than stage II and III. . Mean and standard
      deviation for Hb, Hct, MCV, MCH, MCHC, Fe, TIBC and Ferritin had significant
      difference in infected and non-infected group. CONCLUSION: This study revealed
      that the prevalence of iron deficiency anemia in young girls are moderate, so
      that it is important to reduce the prevalence of iron deficiency anemia in young
      girls.

PMID- 24575288
TI  - Correlation between serum leptin level and thyroid hormones in children with
      major beta-thalassemia .
AB  - BACKGROUND: Beta-thalassemia is the most common hematology disease in human and
      leptin is one of the hormone that produce by adiposities cells. The purpose of
      this study was to investigate the relationship between serum leptin level and
      thyroid hormones in children with major beta-thalassemia. MATERIALS AND METHODS:
      This descriptive-cross sectional study was performed on 90 children aged 6-16
      years old with beta-thalassemia. Body Mass Index (BMI ) were meuseurd in all
      patients and then, after collecting the samples, leptin and thyroid hormones
      levels of the serum were measured in the patients with thalassemia via ELISA
      method. Then, all data was analyzed by Pearson correlation test, and x2
      statistical tests and P < 0.05 was considered as a significant difference.
      RESULTS: The mean of body mass index and serum leptin level in the patients group
      was 16.58+/-2.43 and 1.521 +/-2. 49, respectively. The mean serum levels of
      thyroxin (T4), triiodothyronine (T3), and thyroid- stimulating hormone (TSH) in
      patient's groups were7.94 +/-3.56, 1.28 +/- 0.46, and 2.85 +/-3. 44,
      respectively. There was significant correlation between serum leptin levels and
      T4 in patients with major thalassemia; also there was no significant correlation
      between serum leptin level and T3and TSH. There was a significant correlation was
      between the leptin serum level and BMI in patients (P value=0.008). CONCLUSION:
      The results of this study demonstrated that in patients with major thalassemia,
      there was significant correlation between serum leptin level and thyroxin
      hormone. Leptin level has more relationship with thyroxin than thyroid-
      stimulating hormone.

PMID- 24575289
TI  - The effect of parental ABO blood group on fetal surveillance.
AB  - BACKGROUND: Several factors may cause infertility and fetal loss. Blood groups
      antigens seem to be implied in the mechanisms of infertility and fetal loss.
      Maternal natural antibody can react against father's blood group antigens on
      spermatozoa. The effects of parental blood group system on infertility and fetal
      surveillance perceived by its manifestation in prezygotic (caused infertility)
      and postzygotic (caused fetal loss) stages. Objective of the present study is to
      determine the effect of parental ABO blood group on fetal surveillance and men
      infertility. MATERIALS AND METHODS: This is a retrospective, cross sectional
      study. Our study was carried out in fertility and infertility center of Yazd
      city. Blood group of 118males (group1:100 males with infertility and group 2: 18
      males with abortion history in female partners) that referred to this center was
      evaluated based on medical document's patients. Data were analyzed with SPSS 16
      software using chi-square test. The results were considered significant when P
      value was <0.05, CI: 0.95. RESULTS: Results indicated that overall distribution
      of blood groups in group 1 was:50%, 25%, 16% and 9% and in group 2:
      56%,27%,11%,6% for blood groups O, A, B and AB respectively. There is a
      significant relationship between male infertility and blood group O (P value =
      0.01). There is also a significant relationship between parental blood group O
      and fetal loss in group 2 (P value =0.03). CONCLUSION: The present study revealed
      that there is a significant relationship between father's blood group O and fetal
      loss, so that appropriate intervention strategies can be followed.

PMID- 24575290
TI  - Evaluation the dentists' awareness of inherited bleeding disorders and
      anticoagulants in Shiraz.
AB  - BACKGROUND: Some of the dental procedures can cause bleeding. Bleeding control
      can be difficult in some patients because of systemic disease or chronic
      anticoagulant therapy, so they may be at increased risk for bleeding occurrences
      or even death following invasive dental procedures. This study was schemed to
      measure the knowledge of general dentists in Shiraz city regarding coagulation
      tests performed in bleeding disorders during 2011 to 2012. MATERIALS AND METHODS:
      In this descriptive-analytical study, a questionnaire (consist 23 questions) was
      designed with the help of specialists in the field of oral medicine and
      hematology. This questionnaire was distributed among 146 general practitioners.
      Collected information was analyzed with SPSS version 16. RESULTS: The mean mark
      for dentist's knowledge was 9.40 +/- 1.30 (categorized moderate level). There was
      no significant difference in the mean knowledge scores among male and female
      dentists. Tukey's test displayed a significant difference in the mean knowledge
      level among 21 to 30 years old and over forty years' old dentists (p< 0.03).
      CONCLUSIONS: This study showed that knowledge of the dentists regarding bleeding
      disorders is not at optimal level which needs planning for continuing education
      courses.

PMID- 24575291
TI  - Current understanding in diagnosis and management of factor XIII deficiency.
AB  - Factor XIII or "fibrin-stabilizing factor," is a transglutaminase circulates in
      the blood circulation as a hetero tetramer with two catalytic A subunits and two
      carrier B subunits. This important coagulation factor has a crucial role in
      clotting cascade and produces strong covalent bonds between soluble formed fibrin
      monomers during coagulation. This stable cross linked fibrin strands are
      resistanttodegradationby thefibrinolyticsystem that enablesthe bodyto
      stoppotential bleeding episodes. In the absence or severe decrease of factor
      XIII, although the clot is formed, but is rapidly degraded by the fibrinolytic
      system, and delayed bleedingoccurs.Factor XIII deficiency is an extremely rare
      bleeding disorder with estimated incidence of 1/2-3000, 000 in the general
      population. Presumptive diagnosis of factor XIII deficiency was by clot
      solubility test in 5M urea or 1% monochloroacetic acid environments. In patients
      with abnormal screening clot solubility test, the disease can be confirmedbymore
      specifictestssuch as quantitative factor XIII activity assay
      andFXIIIAgassay.After diagnosis of disease all patients with severe factor XIII
      deficiency(<1 U/dl) shouldreceive prophylactic substitution therapywith fresh
      frozen plasma (FFP) and cryoprecipitate as traditional choices or purified
      concentrateof blood coagulation factor XIII (Fibrogammin P) inorder to control
      severe and life-threatening clinical complications of factor XIII deficiency. 

PMID- 24575292
TI  - Gaucher's Disease, an Unusual Cause of Massive Splenomegaly, a Case Report.
AB  - BACKGROUND: Gaucher's Disease (G.D.) is an autosomal recessive disorder resulting
      from the accumulation of glucocerebrosidase in the cells of macrophage-monocyte
      system as a result of a deficiency in lysosomal glucocerebrosidase. This enzyme
      is encoded by a gene on chromosome-1. Here we report a case of Gaucher's Disease
      .G.D is rare in Yazd. CASE REPORTS: We reported a patient that presented with
      weakness, pallor and gradually increasing abdominal girth. Clinical examination
      and history pointed to be a lipid storage disease. Final diagnosis of G.D. was
      reported after examining the bone marrow smears. Confirmation of diagnosis on
      Gaucher's disease was performed by measurement of glucocerebrosidase level.
      CONCLUSION: We report a case of G.D. to emphasize the importance of early
      recognition by clinical manifestation and histological findings. G.D. should be
      considered in the differential diagnosis of children with unexplained
      splenomegaly.

PMID- 24575293
TI  - Relations between cognitive status and medication adherence in patients treated
      for memory disorders.
AB  - Medication adherence has been increasingly recognized as an important factor in
      elderly persons' health. Various studies have shown that medication non-adherence
      is associated with poor health status in this population. As part of a study of
      the effects of two interventions to promote medication adherence in patients
      treated for memory problems, information on medication adherence and cognitive
      status was collected at 3-month intervals. Twenty-seven participants (16 men, 11
      women, age 71-92 years) were assigned to control or treatment conditions and
      adherence was evaluated with an electronic monitoring device. Cognitive status
      was evaluated at 3-month intervals beginning in April of 2003 and continuing
      through September of 2006. We have previously reported on the effectiveness of
      these interventions to promote adherence. In this paper, we examine the relations
      of cognitive status and adherence over time using a partial least squares path
      model in order to evaluate the extent to which adherence to cholinesterase
      medications was related to cognitive status. Adherence predicted cognitive status
      at later time points while cognition did not, in general, predict adherence.
      Results thus suggest that interventions to ensure high levels of medication
      adherence may be important for maintaining cognitive function in affected elderly
      people.

PMID- 24575294
TI  - Interplay between polymorphisms and methylation in the H19/IGF2 gene region may
      contribute to obesity in Mexican-American children.
AB  - Imprinted genes often affect body size-related traits such as weight. However,
      the association of imprinting with obesity, especially childhood obesity, has not
      been well studied. Mexican-American children have a high prevalence, approaching
      50%, of obesity and/or overweight. In a pilot study of 75 Mexican-American
      children, we analyzed the relationships among obese/overweight status,
      methylation status and single-nucleotide polymorphism (SNP) status at a CpG site
      in a differentially methylated region (DMR) of the imprinted H19/IGF2 locus. We
      observed a significant difference in SNP rs10732516 frequency between boys and
      girls among the overweight and obese children but not among the lean children. We
      also found that children with lower methylation of the polymorphic CpG site
      (CpG4) in the H19 DMR had higher birth weights than did children with higher
      methylation (P = 0.04). Our results suggest that CpG4 methylation status may be
      associated with childhood obesity in Mexican-American children in a sex-specific
      manner. 

PMID- 24575295
TI  - A NIR Dye for Development of Peripheral Nerve Targeted Probes.
AB  - Current imaging modalities lack the ability to quickly assess and classify nerve
      injury for predicting favourable versus unfavourable healing outcomes, which
      could minimize episodes of chronic pain and loss of function by allowing for
      early intervention. Thus, the development of a technique to noninvasively assess
      peripheral nerve damage is of critical importance. While the development of nerve
      specific near infrared (NIR) molecular probes capable of such diagnostics
      constitutes our long term goal, initial studies to identify a NIR dye for
      constructing such a probe are required. We have evaluated the properties of a
      novel highly hydrophilic and functionalizable polymethine dye, and its more
      hydrophobic analogue indocyanine green, within the sciatic nerve of rats
      following intra-nerve injection. The reporting ability of both dyes at critical
      depths for nerve imaging, the importance of hydrophilicity on dye transport
      through nervous tissue, and their toxicity - or lack thereof - to the neural
      environment have been evaluated. The results suggest that the novel NIR dye is an
      appropriate fluorescent reporter for use in designing nerve-specific optical
      molecular probes for non-invasive diagnosis and classification of nerve injury.

PMID- 24575296
TI  - Is there a specific fracture 'cascade'?
AB  - Different kinds of epidemiologic data provide varying views of the relationships
      among the main osteoporotic fractures. Descriptive incidence data indicate that
      distal forearm fractures typically occur earlier than vertebral fractures that,
      in turn, precede hip fractures late in life. In addition, relative risk estimates
      document the fact that one osteoporotic fracture increases the risk of subsequent
      ones. These two observations support the notion of a 'fracture cascade' and
      justify the recent emphasis on secondary prevention, that is, more aggressive
      treatment of patients presenting with a fracture in order to prevent recurrences.
      However, the absolute risk of a subsequent fracture given an initial one is
      modest, and the degree to which the second fracture can be attributed to the
      first one is unclear. Moreover, the osteoporotic fractures encountered in the
      majority of patients are the first one experienced, and even these initial
      fractures lead to substantial morbidity and cost. These latter points reemphasize
      the importance of primary prevention, that is, the management of bone loss and
      other risk factors to prevent the first fracture. Continued efforts are needed to
      refine risk assessment algorithms so that candidates for such fracture
      prophylaxis can be identified more accurately and efficiently. 

PMID- 24575298
TI  - First Report of Aprostocetus asthenogmus (Hymenoptera: Eulophidae) in South
      America and Parasitizing Eggs of Triatominae Vectors of Chagas Disease.
AB  - We report for the first time the parasitism of eggs of two triatomine Chagas
      disease vectors, Triatoma infestans and T. vitticeps, by the microhymenopterous
      parasitoid Aprostocetus asthenogmus. We also describe the first identification of
      this parasitoid in South America. A. asthenogmus were captured near unparasitized
      triatomine colonies in the municipality of Vitoria, state of Espirito Santo,
      Brazil, and placed into pots with recently laid triatomine eggs. After 24 days,
      we observed wasps emerging from T. infestans and T. vitticeps eggs. Several
      characteristics of this parasitoid species suggest that it could be a potential
      biological control agent of triatomine species. 

PMID- 24575299
TI  - Advances in neuroimmunology: from bench to bedside.

PMID- 24575297
TI  - Potential For Cell-mediated Immune Responses In Mouse Models Of Pelizaeus
      Merzbacher Disease.
AB  - Although activation of the innate and adaptive arms of the immune system are
      undoubtedly involved in the pathophysiology of neurodegenerative diseases, it is
      unclear whether immune system activation is a primary or secondary event.
      Increasingly, published studies link primary metabolic stress to secondary
      inflammatory responses inside and outside of the nervous system. In this study,
      we show that the metabolic stress pathway known as the unfolded protein response
      (UPR) leads to secondary activation of the immune system. First, we observe
      innate immune system activation in autopsy specimens from Pelizaeus-Merzbacher
      disease (PMD) patients and mouse models stemming from PLP1 gene mutations.
      Second, missense mutations in mildly- and severely-affected Plp1-mutant mice
      exhibit immune-associated expression profiles with greater disease severity
      causing an increasingly proinflammatory environment. Third and unexpectedly, we
      find little evidence for dysregulated expression of major antioxidant pathways,
      suggesting that the unfolded protein and oxidative stress responses are
      separable. Together, these data show that UPR activation can precede innate
      and/or adaptive immune system activation and that neuroinflammation can be
      titrated by metabolic stress in oligodendrocytes. Whether-or-not such activation
      leads to autoimmune disease in humans is unclear, but the case report of steroid
      mitigated symptoms in a PMD patient initially diagnosed with multiple sclerosis
      lends support. 

PMID- 24575300
TI  - Assistance for the prescription of nutritional support must be required in
      nonexperienced nutritional teams.
AB  - The aim of the study was to determine the current practices of nutritional
      support among hospitalized patients in nonspecialized hospital departments.
      Materials and Methods. During an observation period of 2 months, a surgeon and a
      gastroenterologist designated in each of the two departments concerned, not
      "specialized" in nutritional assistance, have treated patients in which
      nutritional support seemed necessary. Assessing the degree of malnutrition of the
      patient, the therapeutic decision and the type of product prescribed by the
      doctors were secondarily compared to the proposals of a structured computer
      program according to the criteria and standards established by the institutions
      currently recognized. Results. The study included 120 patients bearing a surgical
      disease in 86.7% of cases and 10% of medical cases. 50% of the patients had
      cancer. Nutritional status was correctly evaluated in 38.3% by the initial
      doctors' diagnosis-consistent with the software's evaluation. The strategy of
      nutrition was concordant with the proposals of the software in 79.2% of cases.
      Conclusions. Despite an erroneous assessment of the nutritional status in more
      than two-thirds of cases the strategy of nutritional management was correct in
      80% of cases. Malnutrition and its consequences can be prevented in
      nonexperienced nutritional teams by adequate nutritional support strategies
      coming from modern techniques including computerized programs. 

PMID- 24575301
TI  - (68)Ga-NOTA-CHSg and (99m)Tc-CHSg Labeled Microspheres for Lung Perfusion and
      Liver Radiomicrospheres Therapy Planning.
AB  - Fast biodegradable (12 h < half-life < 48 h) radioactive labeled microspheres are
      needed for PET and SPECT lung perfusion and radiomicrosphere therapy planning. An
      emulsion method was used to create 30.1 +/-4.8  MU m size range microspheres with
      biodegradable Chitosan glycol (CHSg). Microspheres were characterized and labeled
      with (99m)Tc or (68)Ga as an alternative to MAA in perfusion PET and SPECT
      studies. Surface decoration of CHSg microspheres with p-SCN-Bn-NOTA was performed
      to increase (68)Ga  in vivo stability. (99m)Tc was labeled directly to the CHSg
      microspheres. Labeling yield and in vitro radiochemical stability were evaluated.
      In vitro CHSg microsphere degradation half-life was ~24 hours in porcine blood.
      Labeled microspheres were injected into Sprague Dawley rats and biodistribution
      was determined after 2 and 4 hours. Both (99m)Tc-CHSg and (68)Ga-NOTA-CHSg were
      quickly allocated in the lungs after injection. (99m)Tc-CHSg showed 91.6 +/- 6.5%
      and 83.2 +/- 4.1% of the decay corrected injected activity remaining in the lungs
      after 2 and 4 hours, respectively. For the obtained (68)Ga-NOTA-CHSg
      microspheres, lung allocation was very high with 98.9 +/- 0.2% and 95.6 +/- 0.9%
      after 2 and 4 hours, respectively. The addition of p-SCN-Bn-NOTA acts as a
      radioprotectant eliminating the released (68)Ga activity from the lungs to the
      bladder protecting the other organs. 

PMID- 24575302
TI  - The Effect of Community Exercise Interventions for People with MS Who Use
      Bilateral Support for Gait.
AB  - Background. Mobility limitations are a key feature of MS and 25% will require the
      use of a walking aid 15 years after diagnosis. Few studies have specifically
      evaluated the effectiveness of physiotherapy and exercise interventions delivered
      in the community for those with significant disability. Methods. An assessor
      blind, block randomised, and controlled study recruited participants who required
      bilateral assistance for gait and who occasionally used wheelchairs for longer
      distances. They were randomised to 10 weeks of group physiotherapy (balance and
      strengthening exercises), individual physiotherapy, yoga group, or a control
      group. Results. Repeated measures ANOVA found significant time effects for
      physical component of MSIS-29v2 (f = 7.993, P = 0.006) and MFIS (f = 8.695, P =
      0.004). The group * time interaction was significant for the BBS (f = 4.391, P =
      0.006). Post hoc analysis revealed no difference between group and individual
      physiotherapy for BBS. There was no significant difference between groups but the
      6MWT improved for individual physiotherapy (P = 0.001) and MSIS-29v2
      psychological score for group physiotherapy (P = 0.005). Discussion. This study
      found that balance and strengthening exercises, delivered in the community to
      those with significant mobility limitations, improve balance. The effect on
      walking endurance and patient-reported outcomes are unclear and warrants further
      investigation with a larger control group with similar baseline characteristics
      to the intervention groups. 

PMID- 24575304
TI  - A cross-sectional prospective study of cutaneous lesions in newborn.
AB  - Background. Cutaneous alterations are common in neonates. The majority of lesions
      are physiological, transient, or self-limited and require no therapy. Although
      much has been reported on the various disorders peculiar to the skin of infant,
      very little is known about variations and activity of the skin in neonates.
      Objective. To study the various pattern of skin lesions in newborn and to
      estimate the prevalence of physiological and pathological skin lesions in
      newborn. Methods. A total of 1000 newborns were examined in a hospital-based,
      cross-sectional prospective study in the period of November 2007 to May 2009.
      Results. The physiological skin changes observed in order of frequency were
      sebaceous gland hyperplasia (89.4%), Epstein pearls (89.1%), Mongolian spot
      (84.7%), knuckle pigmentation (57.9%), linea nigra (44.5%), hypertrichosis
      (35.3%), miniature puberty (13.3%), acrocyanosis (30.9%), physiological scaling
      (10.8%), and vernix caseosa (7.7%). Of the transient noninfective conditions,
      erythema toxicum neonatorum was seen in 23.2% newborns and miliaria crystallina
      in 3% newborns. The birthmarks in descending order of frequency were salmon patch
      (20.7%), congenital melanocytic nevi (1.9%), and cafe-au-lait macule (1.3%).
      Cutaneous signs of spinal dysraphism were sacral dimple (12.8%), meningomyelocele
      (0.5%), acrochordons (0.1%), and dermoid cyst (0.1%). Conclusion. The
      physiological and transient skin lesions are common in newborns particularly
      sebaceous gland hyperplasia, Epstein pearls, Mongolian spots, and erythema
      toxicum neonatorum. It is important to differentiate them from other more serious
      skin conditions to avoid unnecessary therapeutic interventions. 

PMID- 24575303
TI  - Association between Sleep Disturbances and Leisure Activities in the Elderly: A
      Comparison between Men and Women.
AB  - It has been suggested that physical or social activity is associated with fewer
      sleep disturbances among elderly people. Women report more sleep disturbances
      than men, which could indicate a variation in activity patterns between the
      genders. The aim of this study was to investigate associations between sleep
      disturbances and leisure activities in men and women (n = 945) aged >=60 years in
      a Swedish population. Sleep disturbances were measured using eight dichotomous
      questions and seventeen variables, covering a wide range of leisure activities.
      Few leisure activities were found to be associated with sleep disturbances and
      their importance decreased when the models were adjusted for confounders and
      gender interactions. After clustering the leisure activities and investigating
      individual activities, sociointellectual activities were shown to be significant
      for sleep. However, following adjustment for confounders and gender interactions,
      home maintenance was the only activity significant for sleep. Being a female
      increased the effect of home maintenance. Besides those leisure activities,
      poor/fair self-rated health (OR 7.50, CI: 4.27-11.81) and being female (OR 4.86,
      CI: 2.75-8.61) were found to have the highest association with poor sleep.
      Leisure activities pursued by elderly people should focus on activities of a
      sociointellectual nature, especially among women, to promote sleep. 

PMID- 24575305
TI  - Effect of Women's Decision-Making Autonomy on Infant's Birth Weight in Rural
      Bangladesh.
AB  - Background. Low birth weight (LBW), an outcome of maternal undernutrition, is a
      major public health concern in Bangladesh where the problem is most prominent.
      Women's decision-making autonomy is likely an important factor influencing
      maternal and child health outcomes. The aim of the study was to assess the effect
      of women's decision-making autonomy on infant's birth weight (BW). Methods. The
      study included data of 2175 enrolled women (14-45 years of age) from the Maternal
      and Infant Nutritional Intervention in Matlab (MINIMat-study) in Bangladesh.
      Pearson's chi-square test, analysis of covariance (ANCOVA), and logistic
      regression analysis were applied at the collected data. Results. Women with
      lowest decision-making autonomy were significantly more likely to have a low
      birth weight (LBW) child, after controlling for maternal age, education (woman's
      and her husband's), socioeconomic status (SES) (odds ratio (OR) = 1.4; 95%
      confidence interval (CI) 1.0, 1.8). BW was decreased significantly among women
      with lowest decision making autonomy after adjusting for all confounders.
      Conclusion. Women's decision-making autonomy has an independent effect on BW and
      LBW outcome. In addition, there is a need for further exploration to identify
      sociocultural attributes and gender related determinants of women decision-making
      autonomy in this study setting. 

PMID- 24575306
TI  - Evaluation of Sodium Hyaluronate Lubricating Drops Used before Insertion of
      Contact Lenses on Symptomatology, Severity, and Intensity of Ocular Dryness.
AB  - Purpose. This study aimed to evaluate outcomes from the use of a sodium
      hyaluronate (SH)-based comfort drop, instilled before the insertion of contact
      lenses, in a population of symptomatic contact lens wearers. Methods. This was a
      cross-over, open-label, multi-sites study. Subjects were fitted with silicone
      hydrogel lenses and followed for two months. Before insertion of the lenses, SH
      drops was instilled in the lens for half of the group. The other half did the
      same on the second month. Objectives and subjective outcomes were measured and
      compared before from baseline with the ones collected after usage of SH drops. 

PMID- 24575307
TI  - Endodontic treatment of fused teeth with talon cusp.
AB  - Tooth anomalies are rare phenomena that may be reported by patients as chief
      complaints or may be discovered by dentists in the oral examination. In a few
      cases, rare anomalies are found together in one mouth. Decision to treat such
      anomalies depends on whether or not they interfere with function and esthetics
      and also the patient's preference. In the present case, a 19-year-old male
      presented with two right maxillary fused central and lateral incisors and a
      geminated left maxillary central incisor. A talon-like projection was found at
      the junction site of the fused teeth. His chief complaint was sensitivity to cold
      at the site of the giant fused tooth. This report describes the process of
      diagnosis and treatment of the two anomalies according to patient preference and
      needs. 

PMID- 24575308
TI  - Primary intraparenchymal squamous cell carcinoma of the kidney: a rare and unique
      entity.
AB  - Primary squamous cell carcinoma (SCC) of the renal parenchyma is a very unusual
      entity which needs to be differentiated from primary SCC of renal pelvis, SCC
      from another primary site, and urothelial carcinoma with extensive squamous
      differentiation. We are most probably describing the second case of primary SCC
      of the renal parenchyma in a 51-year-old male who presented with heaviness of
      right upper abdomen with intermittent pain in right flank. Contrast-enhanced
      computed tomography (CECT) revealed a mass in the right lower pole of the kidney
      and histopathology following nephrectomy displayed the features of well
      differentiated squamous cell carcinoma without urothelial involvement. 

PMID- 24575309
TI  - Drug Interaction between Sirolimus and Ranolazine in a Kidney Transplant Patient.
AB  - Purpose. The case of a kidney transplant recipient who experienced a probable
      drug interaction between sirolimus and ranolazine is reported. Summary. The
      narrow therapeutic window of immunosuppressive therapy in transplant recipients
      requires close monitoring for potential drug-drug interactions. The patient, a 57
      year-old Caucasian male kidney transplant recipient, was stable for years on
      sirolimus as his primary immunosuppressive agent and had a history of chronic
      angina, for which he was prescribed ranolazine. Upon addition and dose escalation
      of ranolazine, whole blood sirolimus levels more than tripled, rising to
      immeasurably high concentrations. After holding sirolimus on multiple occasions
      and reducing dosage more than 50%, blood levels returned to therapeutic range,
      while continuing ranolazine. Conclusion. Since ranolazine is a documented P-GP
      and CYP3A inhibitor, and sirolimus a known substrate for both pathways, it is
      proposed that ranolazine inhibition of P-GP and CYP3A4 contributed to the
      significant elevation in sirolimus exposure. No alternative causes for the rise
      in sirolimus exposure were found, and assessment with the Drug Interaction
      Probability Scale finds this interaction to be probable. Clinicians should be
      aware of the potential for this interaction to cause elevated sirolimus exposure
      and subsequent increase in clinical effect or toxicity, in this case
      overimmunosuppression. 

PMID- 24575311
TI  - Effect of iron/folic Acid supplementation on the outcome of malaria episodes
      treated with sulfadoxine-pyrimethamine.
AB  - Folic acid supplementation may potentially alter the efficacy of sulfadoxine
      pyrimethamine (SP) treatment in children with malaria. However, there is lack of
      evidence from randomized controlled trials and effects of folic acid
      supplementation on clinical efficacy of SP therapy remain moderately understood
      among children. In a double masked, placebo-controlled trial among preschool
      children in Pemba Island (Tanzania), iron and folic acid supplementation (Fe/FA)
      showed an increased risk of hospitalizations and death. In the present paper, we
      evaluated if folic acid supplementation reduced the efficacy of malaria treatment
      and thereby contributed to observed adverse effects. During the study, 1648
      children had confirmed malarial episodes and received either sulphadoxine
      pyrimethamine (SP) treatment and iron folic acid or SP treatment and placebo.
      These children were evaluated for recovery and incidence of hospitalization
      during the next 15, 30, and 140 days. Two groups did not differ in malarial
      episode or hospitalization rate on subsequent 15, 30, and 140 days. Altered
      efficacy of SP by folic acid was not observed and did not contribute to adverse
      events in the previous trial. This trial is registered with Controlled-trials.com
      ISRCTN59549825. 

PMID- 24575310
TI  - Mode of Action and Specificity of Bacillus thuringiensis Toxins in the Control of
      Caterpillars and Stink Bugs in Soybean Culture.
AB  - The bacterium Bacillus thuringiensis (Bt) produces delta-endotoxins that possess
      toxic properties and can be used as biopesticides, as well as a source of genes
      for the construction of transgenic plants resistant to insects. In Brazil, the
      introduction of Bt soybean with insecticidal properties to the velvetbean
      caterpillar, the main insect pest of soybean, has been seen a promising tool in
      the management of these agroecosystems. However, the increase in stink bug
      populations in this culture, in various regions of the country, which are not
      susceptible to the existing genetically modified plants, requires application of
      chemicals that damage the environment. Little is known about the actual toxicity
      of Bt to Hemiptera, since these insects present sucking mouthparts, which hamper
      toxicity assays with artificial diets containing toxins of this bacterium. In
      recent studies of cytotoxicity with the gut of different hemipterans,
      susceptibility in the mechanism of action of delta-endotoxins has been
      demonstrated, which can generate promising subsidies for the control of these
      insect pests in soybean. This paper aims to review the studies related to the
      selection, application and mode of action of Bt in the biological control of the
      major pest of soybean, Anticarsia gemmatalis, and an analysis of advances in
      research on the use of Bt for control hemipterans. 

PMID- 24575312
TI  - Enhancing postgraduate learning and teaching: postgraduate summer school in dairy
      science.
AB  - Dairy science is a multidisciplinary area of scientific investigation and Ph.D.
      students aiming to do research in the field of animal and/or veterinary sciences
      must be aware of this. Ph.D. students often have vast spectra of research
      interests, and it is quite challenging to satisfy the expectation of all of them.
      The aim of this study was to establish an international Ph.D. training program
      based on research collaboration between the University of Sydney and the
      University of Padova. The core component of this program was a two-week
      Postgraduate Summer School in Dairy Science, which was held at the University of
      Padova, for Ph.D. students of both universities. Therefore, we designed a program
      that encompassed seminars, workshops, laboratory practical sessions, and farm
      visits. Participants were surveyed using a written questionnaire. Overall,
      participants have uniformly praised the Summer School calling it a rewarding and
      valuable learning experience. The Ph.D. Summer School in Dairy Science provided
      its participants a positive learning experience, provided them the opportunity to
      establish an international network, and facilitated the development of
      transferable skills. 

PMID- 24575314
TI  - Pharmacokinetics of PEGylated Recombinant Human Erythropoietin in Rats.
AB  - rHuEPO plays a central role as chemicals for the treatment of many diseases. Due
      to its short half-life, the main aim for this pharmacokinetic study is to
      investigate a newly developed PEG-rHuEPO with large molecular weight in SD rats.
      After a single intramuscular administration of different doses of 125I-PEG
      rHuEPO, pharmacokinetic parameters, tissue distribution, and excretion were
      analyzed. In in vivo half-life time measured after 125I-PEG-rHuEPO administration
      at the doses of 1, 2, and 3 MUg/kg, t1/2alpha was 1.90, 1.19, and 2.50 hours,
      respectively, whereas t1/2beta was 22.37, 26.21, and 20.92 hours, respectively;
      at 8, 24, and 48 hours after intramuscular administration, PEG-rHuEPO was
      distributed to all of the examined tissues, however, with high concentrations of
      radioactivity, only in plasma, blood, muscle at the administration site, and bone
      marrow. Following a 2 MUg/kg single intramuscular administration, approximately
      21% of the radiolabeled dose was recovered after almost seven days of study.
      Urine was the major route of excretion; 20% of the administered dose was
      recovered in the urine, while excretion in the feces was less than 1.4%.
      Therefore, this PEG-rHuEPO has potential to be clinically used and could reduce
      frequency of injection. 

PMID- 24575313
TI  - Antioedematous and Analgesic Properties of Fertile Fronds of Drynaria
      quercifolia.
AB  - Inflammation is a complex biological response of tissue cells to harmful stimuli
      including trauma, tissue necrosis, and infections which plays a key role in the
      pathophysiology of many deadly diseases. In ethnomedicine Drynaria quercifolia
      fronds are used to treat inflammation as poultice on swellings and as
      antibacterial, hepatoprotective, and antipyretic agent. Herein, we have evaluated
      the antioedematous, antiproliferative, and analgesic properties of the ethanolic
      extract of fertile fronds of D. quercifolia (FF) by standard procedures. Oral
      administration of FF produced significant inhibition of carrageenan and histamine
      induced paw oedema in Wistar rats. FF significantly reduced both wet weight and
      dry weight of granuloma tissue which shows the inhibitory effect on exudative and
      proliferative phases of inflammation. FF significantly attenuated acute and
      delayed phases of formalin induced pain, acetic acid-induced writhing, capsaicin
      induced nociception, and hot plate test in mice. Phytochemical analysis revealed
      the presence of coumarins, flavonoids, glycosides, phenolics, saponins, steroids,
      tannins, and terpenoids. Total phenolic content was 186 mg/g equivalent of gallic
      acid. The HPLC estimation showed flavanone glycoside naringin (1.2%) and its
      aglycone naringenin (0.02%). The presence of potent anti-inflammatory and
      analgesic principles in FF and their synergistic action may be the reason for the
      proposed therapeutic effects. 

PMID- 24575315
TI  - Body Fat Mass Assessment: A Comparison between an Ultrasound-Based Device and a
      Discovery A Model of DXA.
AB  - Objective. To examine measurement of body composition by ultrasound compared with
      a reference technique:dual energy X-ray absorptiometry (DXA). We evaluated the
      accuracy of a portable ultrasound-based device in estimating total body fat mass
      with those assessed by DXA in adult. Methods. Body fat mass has been estimated
      using a portable ultrasound-based device in comparison with a contemporary
      reference DXA apparatus: the Hologic Discovery A. Anthropometric data has been
      assessed in order to maximize the output of the software associated with the
      ultrasound-based device. A cross-validation between ultrasound technique (US) and
      DXA was developed in this study. Total body fat mass estimated by ultrasound was
      compared with this DXA model in a sample of 83 women and 41 men. Results.
      Ultrasound technique (US) of body fat (BF) was better correlated with DXA in both
      women (r (2) = 0.97, P < 0.01) and men (r (2) = 0.92, P < 0.01) with standard
      errors of estimates (SEE) being 2.1 kg and 2.2 kg, respectively. Conclusion. The
      use of a portable device based on a US produced a very accurate BF estimate in
      relation to DXA reference technique. As DXA absorptiometry techniques are not
      interchangeable, the use of our ultrasound-based device needs to be recalibrated
      on a more contemporary DXA. 

PMID- 24575316
TI  - Efficacy of a new video-based training model in spinal surgery.
AB  - BACKGROUND: An important part of neurosurgical training is the improvement of
      surgical skills. Acquiring microsurgical skills follows a learning curve,
      influenced by specific exercises, feedback, and training. Aim of training should
      be rapid learning success. The study shows the way in which video-based training
      can influence the learning curve. METHODS: Over a period of 18 months (2011-2012)
      12 residents were evaluated in spinal surgery (12 cases per resident) by a
      skilled evaluator based on different criteria. The evaluation criteria
      (exposition of important anatomy, intraoperative bleeding, efficacy of using
      bipolar cauterization) were weighted and added to a single quality-score. The
      participating residents were divided into two groups. Only one group (n = 5)
      received video-based training. RESULTS: Residents showed an individually
      different but explicit increase in microsurgical skills. The quality-score during
      the first surgery compared with the end point of the study demonstrated a faster
      improvement of surgical skills in the group with video-based training than in the
      group without special training. Considering all residents together, the video
      training group displayed a steeper gradient of microsurgical success. Comparison
      of the single resident's microsurgical skills showed individual disparities.
      Various biases that influence the learning success are under examination.
      CONCLUSION: Video-based training can improve microsurgical skills, leading to an
      improved learning curve. An earlier entry of the learning curve plateau in the
      video-training group promotes a higher acquisition of surgical skills. Because of
      the positive effect, we plan to apply the video-based training model to other
      neurosurgical subspecialties, especially neurovascular and skull base surgery.

PMID- 24575317
TI  - Ruptured venous aneurysm of cervicomedullary junction.
AB  - BACKGROUND: Ruptured venous aneurysm is often seen with arterio-venous
      malformation (AVM) or developmental venous anomaly (DVA). However, isolated
      venous aneurysm is unusual. CASE DESCRIPTION: We present a case of ruptured
      venous aneurysm that presented with subarachnoid hemorrhage (SAH) and
      intraventricular hemorrhage (IVH). Digital substraction angiography (DSA)
      revealed a saccular contrast filling pouch in the left lateral aspect of
      cervicomedullary junction (CMJ). Endovascular intervention was not a viable
      option. During surgery, a saccular pliable structure approx. 1.5 * 1 cm was found
      in the subarachnoid space that was clipped and excised. There were no arterial
      feeders, no evidence of surrounding AVM, and no dilated perimedullary vein.
      CONCLUSION: This is perhaps the first reported case of ruptured venous aneurysm
      (without associated AVM) of CMJ, which was successfully managed surgically. The
      possible etiologies remain an unnoticed head trauma or a congenital vessel wall
      abnormality. Surgically clipping and excision remains the treatment of choice for
      such lesion.

PMID- 24575318
TI  - Convexity meningiomas enhanced by sodium fluorescein.
AB  - BACKGROUND: The resection of the meningiomas surrounding the dura is an important
      goal during the removal of a convexity meningioma. The authors present the first
      application of sodium fluorescein (SF) as a tool for tumor and dural tail
      identification in convexity meningiomas. METHODS: Five frontal convexity
      meningiomas operated on between December 2012 and April 2013 were included. After
      initial dissection a dose of 1 g of the SF, 20% was injected into a peripheral
      vein. Tumor and dural tail were removed using the correlation between magnetic
      resonance imaging (MRI) findings and transoperative SF enhancement. RESULTS:
      Simpson Grade 1 removal was obtained in three cases, grade 2 in one atypical
      meningioma and grade zero in one case. SF dural tail enhancement was positive in
      all cases and histologic analysis evidenced involvement of the dura by tumors.
      CONCLUSION: SF enhancement was evident in meningiomas and dura surrounding the
      lesions. Histologic analysis confirmed dural involvement. SF could represent an
      universally available fluorescent tool for meningioma surgery.

PMID- 24575319
TI  - C7 intralaminar screw placement, an alternative to lateral mass or pedicle
      fixation for treatment of cervical spondylytic myelopathy, kyphotic deformity,
      and trauma: A case report and technical note.
AB  - BACKGROUND: The authors present a case to illustrate the necessity and technical
      feasibility of C7 laminar screw placement for treatment of sub-axial cervical
      spondylitic myelopathy. The indications for C7 lateral mass screw placement was
      required internal fixation, with small lateral masses (8 mm) and pedicles (4 mm).
      CASE DESCRIPTION: A 67-year-old female with compressive myelopathy after a fall
      from standing is presented. Magnetic resonance (MR) imaging of the cervical spine
      showed severe C3-6 spondylosis with canal and foraminal compromise. Computed
      tomography of the cervical spine confirmed the MR imaging findings as well as
      showed suboptimal lateral mass and pedicles for screw placement. The patient
      underwent a C3-6 laminectomy, C3-6 lateral mass, and C7 laminar screw placement.
      Postoperatively, the patient recovered without complication. CONCLUSION: Internal
      fixation of the cervical spine after iatrogenic destabilization by decompression
      of neural elements secondary to advanced spondylosis can be technically
      challenging. Anatomical landmarks needed for safe placement of lateral mass or
      pedicle instrumentation are often distorted by the patients' advanced pathology
      or Inherent biology. The C7 screw is a key structural element to a long construct
      and therefore necessitates large lateral masses or pedicles to safely place a
      functional screw. C7 laminar screws may be placed safely without fluoroscopic
      guidance when sufficient C7 lateral mass or pedicle screws are not possible or
      with undue risk.

PMID- 24575320
TI  - Subarachnoid hemorrhage due to nonbranching aneurysm of the middle cerebral
      artery in a young adult with a history of Kawasaki disease.
AB  - BACKGROUND: The incidence of subarachnoid hemorrhage (SAH) in young adults is
      relatively rare. Kawasaki disease is a systemic vasculopathy that is known to
      cause coronary artery aneurysms; however, its effect on cerebral arteries remains
      largely unclear. CASE DESCRIPTION: We report the case of a 20-year-old male with
      a history of Kawasaki disease who presented with SAH caused by the rupture of a
      nonbranching middle cerebral artery aneurysm. This is the third report of SAH
      associated with Kawasaki disease. Preoperative echocardiography of the patient
      rejected the presence of bacterial endocarditis and other heart abnormalities. An
      emergency craniotomy and clip occlusion of the aneurysm was successfully
      performed without obstructing the parent artery. Two weeks later, the patient was
      discharged without any apparent neurological deficit. We also performed a
      circumstantial pathological study on specimens obtained from the aneurysm wall.
      Our histological findings suggest that the elastic lamina and tunica intima were
      completely destroyed during the acute vasculitis phase of Kawasaki disease, which
      possibly led to the aneurysmal formation. CONCLUSIONS: Lack of active
      inflammatory changes and atherosclerotic lesions may explain the chronic feature
      of Kawasaki disease, not a typical aneurysmal formation.

PMID- 24575321
TI  - Gowers' intrasyringeal hemorrhage associated with Chiari type I malformation in
      Noonan syndrome.
AB  - BACKGROUND: Idiopathic hemorrhage in a syrinx is a rare entity known as Gowers'
      intrasyringeal hemorrhage. Bleeding confined to the syrinx cavity causes severe,
      sometimes acute, neurological deficits. We report a case of intrasyringeal
      hemorrhage into a preexisting lumbosacral syrinx associated with Chiari type I
      malformation. CASE DESCRIPTION: A 39-year-old female with Noonan syndrome
      underwent foramen magnum decompression and a cervical syrinx-subarachnoid shunt
      for Chiari type I malformation-associated syringomyelia 7 years ago. She
      presented progressive gait deterioration and acute urinary dysfunction,
      indicating conus medullaris syndrome. Initial magnetic resonance imaging revealed
      massive hemorrhage in the intrasyringeal cavity of the conus medullaris. The
      patient underwent surgical removal of the intrasyringeal hematoma and her
      neurological symptoms improved postoperatively. CONCLUSION: Although Gowers'
      intrasyringeal hemorrhage is rare, this entity should be taken into consideration
      in patients with syringomyelia showing acute neurological deterioration.

PMID- 24575322
TI  - Comparison of surgical and endovascular approach in management of spinal dural
      arteriovenous fistulas: A single center experience of 27 patients.
AB  - BACKGROUND: Spinal dural arteriovenous fistula (SDAVF) is a rare spinal vascular
      malformation with an annual incidence of 5-10 cases per million. The data on
      efficacy, recurrence rates and complications of endovascular versus surgical
      treatment of SDAVF is limited. METHODS: We conducted a retrospective chart review
      of 27 adult patients with a diagnosis of SDAVF and who underwent treatment at
      Duke University Hospital between January 1, 1993 and December 31, 2012. We
      compared the outcome measures by Aminoff-Logue score (ALS) in patients who
      underwent treatment with endovascular embolization versus surgical ligation of
      fistula. We compared complication rates, recurrence rates as well as data on long
      term follow up in these patients. RESULTS: Out of 27 patients in the study, 10
      patients underwent endovascular embolization (Onyx was used in 5 patients and
      NBCA in 5 patients) as the first line therapy. Seventeen patients underwent
      surgical ligation as initial therapeutic modality. Patients in both groups showed
      significant improvement in clinical status (ALS) after treatment. One patient in
      endovascular group developed spinal infarction due to accidental embolization of
      medullary artery. Three patients in embolization group had recurrence of fistula
      during the course of follow up requiring surgical ligation. Two patients in
      surgical group developed local wound infection. None of the patients in surgical
      group had recurrence of fistula during the course of follow up. CONCLUSIONS:
      Endovascular embolization and surgical ligation are effective treatment
      strategies for SDAVF. Our observations show that surgical ligation may offer
      permanent cure without any recurrence. Endovascular approach is associated with
      higher incidence of recurrence, especially with use of onyx.

PMID- 24575324
TI  - Optic nerve glioma: A great mimicker.
AB  - BACKGROUND: Arachnoid proliferation, although rare, is known to occur in
      association with optic gliomas. However, chondroid and chordoid metaplasia has
      not been reported previously. CASE DESCRIPTION: A 27-year-old male presented with
      progressive, painless loss of vision in right eye, associated with vomiting and
      headache for one and a half months. Computed tomography (CT) scan revealed a
      contrast enhancing mass arising from planum sphenoidale. Perioperative findings
      showed the tumor adherent to the right optic nerve and attached to basal dura and
      falx. A clinical impression of an intradural, optic nerve sheath meningioma was
      made. Histopathological examination revealed a glial tumor with adjacent areas
      displaying marked fibroblastic and arachnoid cell proliferation with chondroid as
      well as chordoid differentiation along with myxoid change and dense
      collagenisation. Reticulin stain, immunochemistry with glial fibrillary acid
      protein (GFAP), epithelial membrane antigen (EMA), and S-100 helped to arrive at
      the final diagnosis of optic glioma displaying exuberant arachnoid proliferation
      with cartilaginous metaplasia. CONCLUSION: We report a case of optic nerve glioma
      displaying extensive arachnoid proliferation, chordoid, and cartilaginous
      metaplasia, which mimicked chondrosarcoma or chordoid meningioma, posing a
      diagnostic dilemma. A clinical feedback, simple reticulin stain, and GFAP
      staining is of immense value in such cases to arrive at the correct diagnosis.

PMID- 24575323
TI  - Noninvasive diagnosis and management of spontaneous intracranial hypotension in
      patients with marfan syndrome: Case Report and Review of the Literature.
AB  - BACKGROUND: Spontaneous intracranial hypotension is an uncommon clinical entity.
      Heritable connective tissue disorders (HCTD), such as Marfan syndrome, are
      frequently implicated as an underlying cause, due to dural structural weaknesses
      that predispose patients to spontaneous cerebrospinal fluid (CSF) leak. Due to
      the high prevalence of multi-system disease in HCTD, diagnosis and treatment are
      often complicated. CASE DESCRIPTION: We present a 58-year-old female with Marfan
      syndrome on anticoagulation for a mechanical aortic valve replacement who came to
      medical attention with severe, acute-onset headache following a straining
      episode. Noninvasive magnetic resonance (MR) myelography confirmed thoracic CSF
      extravasations and multiple lumbar diverticula. The patient was treated
      conservatively and her symptoms resolved. CONCLUSION: We discuss the common
      presentation, diagnostic tools, and treatment options for spontaneous CSF leaks
      in patients with Marfan syndrome or related HCTD with an emphasis on noninvasive
      modalities and a review of the major radiographic criteria used to diagnose dural
      abnormalities, such as dural ectasia.

PMID- 24575325
TI  - Temporary clamping of bilateral external carotid arteries for surgical excision
      of a complex dural arteriovenous fistula.
AB  - BACKGROUND: Some complex dural arteriovenous fistulas (DAVFs) are lesions that
      typically have numerous arterial feeders. Surgery, including resection of
      fistulas or skeletonization of the diseased sinus, is still one of the important
      treatments for these lesions. However, major blood loss is usually encountered
      during craniotomy because of abundant arterial feeders from the scalp and
      transosseous vessels. We present a novel approach for obliteration of the
      fistulas with less blood loss. METHODS: Our first case was a 52-year-old male who
      suffered from syncope and seizure. Cerebral digital subtraction angiography (DSA)
      revealed complex DAVFs with numerous arterial feeders from bilateral external
      carotid arteries (ECAs) and drainage into the superior sagittal sinus with
      cerebral venous reflux. The second case was a 48-year-old male presenting with
      chronic headache. His DSA also showed complex DAVFs along the superior sagittal
      sinus with cerebral venous reflux. In both cases, we performed the surgical
      procedure to obliterate the pathological fistulas after temporary clamping of
      bilateral ECAs and noted less blood loss than in the conventional surgery.
      RESULTS: The follow-up DSA showed successful obliteration of the complex DAVFs on
      the first case and partial improvement on the second case followed by
      transarterial embolization (TAE). The symptoms of the both patients were relieved
      after surgery with good recovery. CONCLUSION: Temporary clamping of bilateral
      ECAs can improve the safety and ease the surgical excision for complex DAVFs. By
      using this technique, neurosurgeons can deal with aggressive DAVFs more
      confidently and calmly.

PMID- 24575326
TI  - CULTURAL PHENOMENA AND THE SYNDEMIC FACTOR: SUBSTANCE ABUSE, VIOLENCE, HIV, AND
      DEPRESSION AMONG HISPANIC WOMEN.
AB  - Researchers exploring the health of Hispanics in South Florida utilizing a
      combination of qualitative and quantitative research methods have identified that
      substance abuse, violence, risky sexual behavior, and depression are not only
      conceptualized as tightly interrelated health and social problems, but also hold
      together in a measurement model to represent an underlying phenomenon (i.e., the
      Syndemic Factor). The purpose of this study is to test hypothesized relationships
      between cultural phenomena and the Syndemic Factor among community-dwelling
      Hispanic women. Standardized questionnaires assessing Acculturation, Hispanic
      Stress, Familism, and the Syndemic Factor were administered to a cross-sectional
      sample of 548 Hispanic women from South Florida. Structural equation modeling was
      used to analyze relationships. The model explained 61 percent of the variance in
      the Syndemic Factor. There was a large positive relationship between the Syndemic
      Factor and Hispanic Stress, and a small inverse relationship between the Syndemic
      Factor and Familism. Women with high Hispanic Acculturation and low U.S.
      Acculturation scored lower on the Syndemic Factor than Integrated/Bicultural
      women. Familism buffered the relationship between Hispanic Stress and the
      Syndemic Factor. Structural, community, family, and individual prevention
      strategies that address underlying conditions associated with the Syndemic Factor
      must be developed and formally evaluated.

PMID- 24575327
TI  - Bioartificial Renal Epithelial Cell System (BRECS): A Compact, Cryopreservable
      Extracorporeal Renal Replacement Device.
AB  - Renal cell therapy has shown clinical efficacy in the treatment of acute renal
      failure (ARF) and promise for treatment of end-stage renal disease (ESRD) by
      supplementing conventional small solute clearance (hemodialysis or
      hemofiltration) with endocrine and metabolic function provided by cells
      maintained in an extracorporeal circuit. A major obstacle in the widespread
      adoption of this therapeutic approach is the lack of a cryopreservable system to
      enable distribution, storage, and therapeutic use at point of care facilities.
      This report details the design, fabrication, and assessment of a Bioartificial
      Renal Epithelial Cell System (BRECS), the first all-in-one culture vessel,
      cryostorage device, and cell therapy delivery system. The BRECS was loaded with
      up to 20 cell-seeded porous disks, which were maintained by perfusion culture.
      Once cells reached over 5 * 106 cells/disk for a total therapeutic dose of
      approximately 108 cells, the BRECS was cryopreserved for storage at -80 degrees C
      or -140 degrees C. The BRECS was rapidly thawed, and perfusion culture was
      resumed. Near precryopreservation values of cell viability, metabolic activity,
      and differentiated phenotype of functional renal cells were confirmed post
      reconstitution. This technology could be extended to administer other cell-based
      therapies where metabolic, regulatory, or secretion functions can be leveraged in
      an immunoisolated extracorporeal circuit.

PMID- 24575330
TI  - Myelin Basic Protein-primed T Helper 2 Cells Suppress Microglial Activation via
      AlphaVBeta3 Integrin: Implications for Multiple Sclerosis.
AB  - Multiple sclerosis (MS) is the most common autoimmune demyelinating disease in
      human and T helper type 2 (Th2) cells have been shown to be beneficial for this
      disease. However, mechanisms by which Th2 cells ameliorate disease in MS are
      poorly understood. Microglial activation plays an important role in the
      pathogenesis of MS and other neurodegenerative disorders. Here, we delineate that
      Th2 cells are capable of suppressing microglial activation via cell-to-cell
      contact. After polarization of MBP-primed Th1 cells to Th2 by gemfibrozil and
      other drugs, we observed that MBP-primed Th2 cells dose dependently inhibited the
      production of interleukin-1beta (IL-1beta) and nitric oxide (NO) in LPS
      stimulated microglia via cell-to-cell contact. Similarly, Th2 cells also
      suppressed the microglial inflammatory response in the presence of different
      pathological stimuli of Alzheimer's disease (AD), Parkinson's disease (PD), and
      HIV associated dementia (HAD). Interestingly, Th2 cells expressed higher levels
      of alphaV (alphaV) and beta3 (beta3) integrins as compared to Th1 cells, and
      functional blocking antibodies against alphaV and beta3 integrins impaired the
      ability of Th2 cells to suppress microglial activation. Furthermore, we
      demonstrate that microglia expressed the beta subunit of PDGF receptor
      (PDGFRbeta) and that neutralization of PDGFRbeta abrogated the ability of Th2
      cells to suppress microglial inflammation. Activation of microglial cAMP response
      element-binding (CREB) by Th2 cells, suppression of CREB activation by
      neutralization of either alphaV and beta3 integrins on Th2 cells or PDGFRbeta on
      microglia, abrogation of anti-inflammatory activity of Th2 cells by siRNA
      knockdown of microglial CREB, highlights the importance of alphaVbeta3 and
      PDGFRbeta in guiding the anti-inflammatory activity of Th2 cells via activation
      of CREB, which may be responsible for beneficial effect of Th2 cells in MS and
      other related disorders.

PMID- 24575331
TI  - Non-de-scanned parallel recording two-photon hyperspectral microscopy with high
      spectral and spatial resolution.
AB  - A two-photon hyperspectral microscope with non-de-scanned geometry and parallel
      recording scheme was constructed which had a low dwell time, high spectral
      resolution, and high spatial resolution. The dwell time was effectively decreased
      to reduce photodamage through parallel recording, while the non-de-scanned
      geometry led to a considerable reduction in the signal loss and spectrum
      distortion. Two experiments were performed to show that this system can solve
      crosstalk issues and spectrally resolve the intrinsic fluorophores in optically
      thick tissues without staining and sectioning. 

PMID- 24575328
TI  - Socioeconomic Status and Survival of People with Human Immunodeficiency Virus
      Infection before and after the Introduction of Highly Active Antiretroviral
      Therapy: A Systematic Literature Review.
AB  - BACKGROUND: Human immunodeficiency virus/acquired immunodeficiency disease
      syndrome-associated mortality contributes considerably to overall mortality rates
      among adults in the United States. The purpose of this review is to
      systematically examine conceptual approaches that have been used to evaluate the
      association between socioeconomic status of people infected with human
      immunodeficiency virus and their survival and summarize existing evidence
      regarding the association between socioeconomic status and mortality due to human
      immunodeficiency virus/acquired immunodeficiency disease syndrome. METHODS: We
      systematically retrieved neighborhood and individual-level studies of acquired
      immunodeficiency disease syndrome-related or all-cause mortality among patients
      diagnosed with human immunodeficiency virus that reported original data and
      analyzed socioeconomic status as a predictor of mortality. RESULTS: We included
      21 studies (19 cohort and 2 case-control studies). Heterogeneity in both the
      conceptual approaches to socioeconomic status measurements and selection of
      variables for the adjustment of the measure of association precluded meta
      analysis of the results. Six studies observing populations before the
      introduction of highly active antiretroviral therapy found that socioeconomic
      status was not associated with human immunodeficiency virus/acquired
      immunodeficiency disease syndrome mortality. In the post- highly active
      antiretroviral therapy period socioeconomic status was inconsistently associated
      with Human immunodeficiency virus/acquired immunodeficiency disease syndrome
      mortality risk in studies adjusting for highly active antiretroviral therapy use.
      CONCLUSION: Further studies considering multilevel socioeconomic status
      measurements and controlling for treatment and clinical variables are needed to
      enhance understanding of the role of socioeconomic gradients on human
      immunodeficiency virus outcomes.

PMID- 24575332
TI  - Automatic segmentation of up to ten layer boundaries in SD-OCT images of the
      mouse retina with and without missing layers due to pathology.
AB  - Accurate quantification of retinal layer thicknesses in mice as seen on optical
      coherence tomography (OCT) is crucial for the study of numerous ocular and
      neurological diseases. However, manual segmentation is time-consuming and
      subjective. Previous attempts to automate this process were limited to high
      quality scans from mice with no missing layers or visible pathology. This paper
      presents an automatic approach for segmenting retinal layers in spectral domain
      OCT images using sparsity based denoising, support vector machines, graph theory,
      and dynamic programming (S-GTDP). Results show that this method accurately
      segments all present retinal layer boundaries, which can range from seven to ten,
      in wild-type and rhodopsin knockout mice as compared to manual segmentation and
      has a more accurate performance as compared to the commercial automated Diver
      segmentation software. 

PMID- 24575329
TI  - Engagement with Health Care Providers Affects Self- Efficacy, Self-Esteem,
      Medication Adherence and Quality of Life in People Living with HIV.
AB  - The engagement of patients with their health care providers (HCP) improves
      patients' quality of life (QOL), adherence to antiretroviral therapy, and life
      satisfaction. Engagement with HCP includes access to HCP as needed, information
      sharing, involvement of client in decision making and self-care activities,
      respect and support of the HCP for the client's choices, and management of client
      concerns. This study compares country-level differences in patients' engagement
      with HCP and assesses statistical associations relative to adherence rates, self
      efficacy, self-esteem, QOL, and symptom self-reporting by people living with HIV
      (PLHIV). A convenience sample of 2,182 PLHIV was enrolled in the United States,
      Canada, Puerto Rico, Namibia, and China. Cross-sectional data were collected
      between September 2009 and January 2011. Inclusion criteria were being at least
      18 years of age, diagnosed with HIV, able to provide informed consent, and able
      to communicate in the local language with site researchers. In the HCP scale, a
      low score indicated greater provider engagement. Country comparisons showed that
      PLHIV in Namibia had the most HCP engagement (OR 2.80, p < 0.001) and that PLHIV
      in China had the least engagement (OR -7.03, p < 0.0001) compared to the PLHIV in
      the Western countries. Individuals having better HCP engagement showed better
      self-efficacy for adherence (t = -5.22, p < 0.0001), missed fewer medication
      doses (t = 1.92, p <= 0.05), had lower self-esteem ratings (t = 2.67, p < 0.01),
      fewer self-reported symptoms (t = 3.25, p < 0.0001), and better overall QOL
      physical condition (t = -3.39, p < 0.001). This study suggests that promoting
      engagement with the HCP is necessary to facilitate skills that help PLHIV manage
      their HIV. To improve ART adherence, HCPs should work on strategies to enhance
      self-efficacy and self-esteem, therefore, exhibiting fewer HIV-related symptoms
      and missing less medication doses to achieve better QOL.

PMID- 24575333
TI  - Video-rate structured illumination microscopy for high-throughput imaging of
      large tissue areas.
AB  - We report the development of a structured illumination microscopy instrument
      specifically designed for the requirements for high-area-throughput, optically
      sectioned imaging of large, fluorescently-stained tissue specimens. The system
      achieves optical sectioning frame-rates of up to 33 Hz (and pixel sampling rates
      of up to 138.4 MHz), by combining a fast, ferroelectric spatial light modulator
      for pattern generation with the latest large-format, high frame-rate scientific
      CMOS camera technology. Using a 10X 0.45 NA objective and a 7 mm/sec scan stage,
      we demonstrate 4.4 cm(2)/min area-throughput rates in bright tissue-simulating
      phantoms, and 2 cm(2)/min area-throughput rates in thick, highly-absorbing,
      fluorescently-stained muscle tissue, with 1.3 MUm lateral resolution. We
      demonstrate high-contrast, high-resolution imaging of a fluorescently-stained
      30.4 cm(2) bovine muscle specimen in 15 minutes comprising 7.55 gigapixels,
      demonstrating the feasibility of the approach for gigapixel imaging of large
      tissues in short timeframes, such as would be needed for intraoperative imaging
      of tumor resection specimens. 

PMID- 24575334
TI  - Dynamic autofluorescence imaging of intracellular components inside living cells
      using direct electron beam excitation.
AB  - We developed a high-resolution fluorescence microscope in which fluorescent
      materials are directly excited using a focused electron beam. Electron beam
      excitation enables detailed observations on the nanometer scale. Real-time live
      cell observation is also possible using a thin film to separate the environment
      under study from the vacuum region required for electron beam propagation. In
      this study, we demonstrated observation of cellular components by
      autofluorescence excited with a focused electron beam and performed dynamic
      observations of intracellular granules. Since autofluorescence is associated with
      endogenous substances in cells, this microscope can also be used to investigate
      the intrinsic properties of organelles. 

PMID- 24575335
TI  - Fast and robust reconstruction for fluorescence molecular tomography via a
      sparsity adaptive subspace pursuit method.
AB  - Fluorescence molecular tomography (FMT), as a promising imaging modality, can
      three-dimensionally locate the specific tumor position in small animals. However,
      it remains challenging for effective and robust reconstruction of fluorescent
      probe distribution in animals. In this paper, we present a novel method based on
      sparsity adaptive subspace pursuit (SASP) for FMT reconstruction. Some innovative
      strategies including subspace projection, the bottom-up sparsity adaptive
      approach, and backtracking technique are associated with the SASP method, which
      guarantees the accuracy, efficiency, and robustness for FMT reconstruction. Three
      numerical experiments based on a mouse-mimicking heterogeneous phantom have been
      performed to validate the feasibility of the SASP method. The results show that
      the proposed SASP method can achieve satisfactory source localization with a bias
      less than 1mm; the efficiency of the method is much faster than mainstream
      reconstruction methods; and this approach is robust even under quite ill-posed
      condition. Furthermore, we have applied this method to an in vivo mouse model,
      and the results demonstrate the feasibility of the practical FMT application with
      the SASP method. 

PMID- 24575337
TI  - A hybrid silicon-PDMS optofluidic platform for sensing applications.
AB  - A hybrid silicon-poly(dimethysiloxane) (PDMS) optofluidic platform for lab-on-a
      chip applications is proposed. A liquid-core waveguide with a self-aligned solid
      core waveguide and a microfluidic device are integrated with a multilayer
      approach, resulting in a three-dimensional device assembly. The optofluidic layer
      was fabricated with a hybrid silicon-polymer technology, whereas the microfluidic
      layer was fabricated with a soft lithography technique. The combination of
      different materials and fabrication processes allows a modular approach, enabling
      both the benefits from the high optical quality achievable with silicon
      technology and the low cost of polymer processing. The proposed chip has been
      tested for fluorescence measurements on Cy5 water solutions, demonstrating the
      possibility to obtain a limit of detection of 2.5 nM. 

PMID- 24575336
TI  - Phase-gradient contrast in thick tissue with a scanning microscope.
AB  - It is well known that the principle of reciprocity is valid for light traveling
      even through scattering or absorptive media. This principle has been used to
      establish an equivalence between conventional widefield microscopes and scanning
      microscopes. We make use of this principle to introduce a scanning version of
      oblique back-illumination microscopy, or sOBM. This technique provides sub
      surface phase-gradient and amplitude images from unlabeled tissue, in an epi
      detection geometry. That is, it may be applied to arbitrarily thick tissue. sOBM
      may be implemented as a simple, cost-effective add-on with any scanning
      microscope, requiring only the availability of an extra input channel in the
      microscope electronics. We demonstrate here its implementation in combination
      with two-photon excited fluorescence (TPEF) microscopy and with coherent anti
      Stokes Raman scattering (CARS) microscopy, applied to brain or spinal cord tissue
      imaging. In both cases, sOBM provides information on tissue morphology
      complementary to TPEF or CARS contrast. This information is obtained
      simultaneously and is automatically co-registered. Finally, we show that sOBM can
      be operated at video rate. 

PMID- 24575338
TI  - Position-addressable digital laser scanning point fluorescence microscopy with a
      Blu-ray disk pickup head.
AB  - A compact and position-addressable blue ray scanning microscope (BSM) based on a
      commercially available Blu-ray disk pickup head (PUH) is developed for cell
      imaging with high resolution and low cost. The BSM comprises two objective lenses
      with numerical apertures (NAs) of 0.85 and 0.6 for focusing blue and red laser
      beams, respectively, on the sample slide. The blue and red laser beams are co
      located adjacent to each other and move synchronously. A specially designed
      sample slide is used with a sample area and an address-patterned area for sample
      holding and address recognition, respectively. The blue laser beam is focused on
      the sample area and is used for fluorescent excitation and image capturing,
      whereas the red laser beam is focused on the address-patterned area and is used
      for address recognition and dynamic focusing. The address-patterned area is
      divided into 310 sectors. The cell image of each sector of the sampling area has
      a corresponding address pattern. Fluorescence images of monkey-derived kidney
      epithelial cells and fibroblast cells in which the F-actin is stained with
      fluorophore phalloidin CF 405 are measured by the BSM, with results comparable to
      those measured by a Leica TCS CP2 confocal microscope. The cell image of an area
      of interest can be easily tracked based on the coded address, and a large-area
      sample image can be accurately reconstructed from the sector images. 

PMID- 24575339
TI  - Adaptive optics SLO/OCT for 3D imaging of human photoreceptors in vivo.
AB  - We present a new instrument that is capable of imaging human photoreceptors in
      three dimensions. To achieve high lateral resolution, the system incorporates an
      adaptive optics system. The high axial resolution is achieved through the
      implementation of optical coherence tomography (OCT). The instrument records
      simultaneously both, scanning laser ophthalmoscope (SLO) and OCT en-face images,
      with a pixel to pixel correspondence. The information provided by the SLO is used
      to correct for transverse eye motion in post-processing. In order to correct for
      axial eye motion, the instrument is equipped with a high speed axial eye tracker.
      In vivo images of foveal cones as well as images recorded at an eccentricity from
      the fovea showing cones and rods are presented. 

PMID- 24575340
TI  - Dual-reporter in vivo imaging of transient and inducible heat-shock promoter
      activation.
AB  - Gene promoter activity can be studied in vivo by molecular imaging methods using
      reporter gene technology. Transcription of the reporter and the reported genes
      occurs simultaneously. However, imaging depends on reporter protein translation,
      stability, and cellular fate that may differ among the various proteins. A double
      transgenic mouse strain expressing the firefly luciferase (lucF) and fluorescent
      mPlum protein under the transcriptional control of the thermo-inducible heat
      shock protein (Hspa1b) promoter was generated allowing to follow up the reporter
      proteins by different and complementary in vivo imaging technologies. These mice
      were used for in vivo imaging by bioluminescence and epi fluorescence reflectance
      imaging (BLI & FRI) and as a source of embryonic fibroblast (MEF) for in vitro
      approaches. LucF, mPlum and endogenous Hsp70 mRNAs were transcribed
      simultaneously. The increase in mRNA was transient, peaking at 3 h and then
      returning to the basal level about 6 h after the thermal stimulations. The
      bioluminescent signal was transient and initiated with a 3 h delay versus mRNA
      expression. The onset of mPlum fluorescence was more delayed, increasing slowly
      up to 30 h after heat-shock and remaining for several days. This mouse allows for
      both bioluminescence imaging (BLI) and fluorescence reflectance imaging (FRI) of
      Hsp70 promoter activation showing an early and transient lucF activity and a
      retrospective and persistent mPlum fluorescence. This transgenic mouse will allow
      following the transient local induction of Hsp-70 promoter beyond its induction
      time-frame and relate into subsequent dynamic biological effects of the heat
      shock response. 

PMID- 24575341
TI  - Development of a new pulsed source for photoacoustic imaging based on
      aperiodically poled lithium niobate.
AB  - We present the development of a source of deep-red radiation for photoacoustic
      imaging. This source, which is based on two cascaded wavelength conversion
      processes in aperiodically poled lithium niobate, emits 10 nanosecond pulses of
      over 500 uJ at 710 nm. Photoacoustic images were obtained from phantoms designed
      to mimic the optical and acoustic properties of oral tissue. Results indicate
      this device is a viable source of optical pulses for photoacoustic applications. 

PMID- 24575342
TI  - Thermoelastic displacement measured by DP-OCT for detecting vulnerable plaques.
AB  - The detection of thermoelastic displacement by differential phase optical
      coherence tomography (DP-OCT) was analytically evaluated for identifying
      atherosclerotic plaques. Analytical solutions were developed to understand the
      dynamics of physical distribution of point hear sources during/after laser
      irradiation on thermoelastic responses of MION-injected tissue. Both analytical
      and experimental results demonstrated a delayed peak displacement along with slow
      decay after laser pulse due to heterogeneous distribution of the point heat
      sources. Detailed description of the heat sources in tissue as well as
      integration of a scanning mirror can improve computational accuracy as well as
      clinical applicability of DP-OCT for diagnosing vulnerable plaque. 

PMID- 24575343
TI  - Numerical investigation of two-dimensional light scattering patterns of cervical
      cell nuclei to map dysplastic changes at different epithelial depths.
AB  - We use an extensive set of quantitative histopathology data to construct
      realistic three-dimensional models of normal and dysplastic cervical cell nuclei
      at different epithelial depths. We then employ the finite-difference time-domain
      method to numerically simulate the light scattering response of these
      representative models as a function of the polar and azimuthal scattering angles.
      The results indicate that intensity and shape metrics computed from two
      dimensional scattering patterns can be used to distinguish between different
      diagnostic categories. Our numerical study also suggests that different
      epithelial layers and angular ranges need to be considered separately to fully
      exploit the diagnostic potential of two-dimensional light scattering
      measurements. 

PMID- 24575344
TI  - Orientation-independent rapid pulsatile flow measurement using dual-angle Doppler
      OCT.
AB  - Doppler OCT (DOCT) can provide blood flow velocity information which is valuable
      for investigation of microvascular structure and function. However, DOCT is only
      sensitive to motion parallel with the imaging beam, so that knowledge of flow
      direction is needed for absolute velocity determination. Here, absolute
      volumetric flow is calculated by integrating velocity components perpendicular to
      the B-scan plane. These components are acquired using two illumination beams with
      a predetermined angular separation, produced by a delay encoded technique. This
      technology enables rapid pulsatile flow measurement from single B-scans without
      the need for 3-D volumetric data or knowledge of blood vessel orientation. 

PMID- 24575345
TI  - Fluorescence lifetime spectroscopy of tissue autofluorescence in normal and
      diseased colon measured ex vivo using a fiber-optic probe.
AB  - We present an ex vivo study of temporally and spectrally resolved
      autofluorescence in a total of 47 endoscopic excision biopsy/resection specimens
      from colon, using pulsed excitation laser sources operating at wavelengths of 375
      nm and 435 nm. A paired analysis of normal and neoplastic (adenomatous polyp)
      tissue specimens obtained from the same patient yielded a significant difference
      in the mean spectrally averaged autofluorescence lifetime -570 +/- 740 ps (p =
      0.021, n = 12). We also investigated the fluorescence signature of non-neoplastic
      polyps (n = 6) and inflammatory bowel disease (n = 4) compared to normal tissue
      in a small number of specimens. 

PMID- 24575347
TI  - Wavefront sensorless adaptive optics optical coherence tomography for in vivo
      retinal imaging in mice.
AB  - We present wavefront sensorless adaptive optics (WSAO) Fourier domain optical
      coherence tomography (FD-OCT) for in vivo small animal retinal imaging. WSAO is
      attractive especially for mouse retinal imaging because it simplifies optical
      design and eliminates the need for wavefront sensing, which is difficult in the
      small animal eye. GPU accelerated processing of the OCT data permitted real-time
      extraction of image quality metrics (intensity) for arbitrarily selected retinal
      layers to be optimized. Modal control of a commercially available segmented
      deformable mirror (IrisAO Inc.) provided rapid convergence using a sequential
      search algorithm. Image quality improvements with WSAO OCT are presented for both
      pigmented and albino mouse retinal data, acquired in vivo. 

PMID- 24575346
TI  - In-Vivo functional optical-resolution photoacoustic microscopy with stimulated
      Raman scattering fiber-laser source.
AB  - In this paper a multi-wavelength optical-resolution photoacoustic microscopy (OR
      PAM) system using stimulated Raman scattering is demonstrated for both phantom
      and in vivo imaging. A 1-ns pulse width ytterbium-doped fiber laser is coupled
      into a single-mode polarization maintaining fiber. Discrete Raman-shifted
      wavelength peaks extending to nearly 800 nm are generated with pulse energies
      sufficient for OR-PAM imaging. Bandpass filters are used to select imaging
      wavelengths. A dual-mirror galvanometer system was used to scan the focused
      outputs across samples of carbon fiber networks, 200MUm dye-filled tubes, and
      Swiss Webster mouse ears. Photoacoustic signals were collected in transmission
      mode and used to create maximum amplitude projection C-scan images. Double dye
      experiments and in vivo oxygen saturation estimation confirmed functional imaging
      potential. 

PMID- 24575348
TI  - Advances in optics for biotechnology, medicine and surgery.
AB  - The guest editors introduce a Biomedical Optics Express feature issue that
      includes contributions from participants at the 2013 conference on Advances in
      Optics for Biotechnology, Medicine and Surgery XIII. 

PMID- 24575349
TI  - Non-invasive fluorescence imaging under ambient light conditions using a
      modulated ICCD and laser diode.
AB  - One limitation of fluorescence molecular imaging that can limit clinical
      implementation and hamper small animal imaging is the inability to eliminate
      ambient light. Herein, we demonstrate the ability to conduct rapid non-invasive,
      far-red and near-infrared fluorescence imaging in living animals and a phantom
      under ambient light conditions using a modulated image intensified CCD (ICCD) and
      a laser diode operated in homodyne detection. By mapping AC amplitude from three
      planar images at varying phase delays, we show improvement in target-to
      background ratios (TBR) and reasonable signal-to-noise ratios (SNR) over
      continuous wave measurements. The rapid approach can be used to accurately
      collect fluorescence in situations where ambient light cannot be spectrally
      conditioned or controlled, such as in the case of fluorescent molecular image
      guided surgery. 

PMID- 24575350
TI  - Handheld Diffuse Reflectance Spectral Imaging (DRSi) for in-vivo characterization
      of skin.
AB  - Diffuse reflectance spectroscopy provides a noninvasive means to measure optical
      and physiological properties of tissues. To expand on these measurements, we have
      developed a handheld diffuse reflectance spectral imaging (DRSi) system capable
      of acquiring wide field hyperspectral images of tissue. The image acquisition
      time was approximately 50 seconds for a 50x50 pixel image. A transport model was
      used to fit each spectra for reduced scattering coefficient, hemoglobin
      concentration and melanin concentration resulting in optical property maps. The
      system was validated across biologically relevant levels of reduced scattering
      (5.14% error) and absorption (8.34% error) using tissue simulating phantoms. DRSi
      optical property maps of a pigmented skin lesion were acquired in vivo. These
      trends in optical properties were consistent with previous observations using
      point probe devices. 

PMID- 24575351
TI  - Temporal correlation of spontaneous hemodynamic activity in language areas
      measured with functional near-infrared spectroscopy.
AB  - Functional near-infrared spectroscopy (fNIRS) was used to investigate resting
      state connectivity of language areas including bilateral inferior frontal gyrus
      (IFG) and superior temporal gyrus (STG). Thirty-two subjects participated in the
      experiment, including twenty adults and twelve children. Spontaneous hemodynamic
      fluctuations were recorded, and then intra- and inter-hemispheric temporal
      correlations of these signals were computed. The correlations of all hemoglobin
      components were observed significantly higher for adults than children. Moreover,
      the differences for the STG were more significant than for the IFG. In the adult
      group, differences in the correlations between males and females were not
      significant. Our results suggest by measuring resting state intra- and inter
      hemispheric correlations, fNIRS is able to provide qualitative and quantitative
      evaluation on the functioning of the cortical network. 

PMID- 24575352
TI  - Synthesis and characterization of biocompatible nanodiamond-silk hybrid material.
AB  - A new hybrid material consisting of nanodiamonds (NDs) and silk has been
      synthesized and investigated. NDs can contain bright fluorescence centers,
      important for bioprobes to image biological structures at the nanoscale and silk
      provides a transparent, robust matrix for these nanoparticles in-vivo or in
      vitro. The ND-silk hybrid films were determined to be highly transparent in the
      visible to near infrared wavelength range. The NDs embedded in silk exhibited
      significant enhancement of emission relative to air, correlating with theoretical
      predictions. Furthermore, animal toxicity tests confirmed ND-silk films to be non
      toxic in an in-vivo mice model. 

PMID- 24575353
TI  - Characterization of eosinophilic esophagitis murine models using optical
      coherence tomography.
AB  - Pre-clinical studies using murine models are critical for understanding the
      pathophysiological mechanisms underlying immune-mediated disorders such as
      Eosinophilic esophagitis (EoE). In this study, an optical coherence tomography
      (OCT) system capable of providing three-dimensional images with axial and
      transverse resolutions of 5 um and 10 um, respectively, was utilized to obtain
      esophageal images from a murine model of EoE-like disease ex vivo. Structural
      changes in the esophagus of wild-type (Tslpr(+/+) ) and mutant (Tslpr(-/-) ) mice
      with EoE-like disease were quantitatively evaluated and food impaction sites in
      the esophagus of diseased mice were monitored using OCT. Here, the capability of
      OCT as a label-free imaging tool devoid of tissue-processing artifacts to
      effectively characterize murine EoE-like disease models has been demonstrated. 

PMID- 24575354
TI  - Assessment of local structural disorders of the bladder wall in partial bladder
      outlet obstruction using polarized light imaging.
AB  - Partial bladder outlet obstruction causes prominent morphological changes in the
      bladder wall, which leads to bladder dysfunction. In this paper, we demonstrate
      that polarized light imaging can be used to identify the location of obstruction
      induced structural changes that other imaging modalities fail to detect. We
      induced 2-week and 6-week partial outlet obstruction in rats, harvested
      obstructed bladders, then measured their retardances while distended to high
      pressures and compared them to controls. Our results show that the retardance of
      the central part of the ventral side (above the ureters) closer to the urethra
      can be used as a potential metric of the distending bladder obstruction. 

PMID- 24575356
TI  - Introduction: feature issue on optical molecular probes, imaging, and drug
      delivery.
AB  - The editors introduce the Biomedical Optics Express feature issue "Optical
      Molecular Probes, Imaging, and Drug Delivery," which is associated with a Topical
      Meeting of the same name held at the 2013 Optical Society of America (OSA) Optics
      in the Life Sciences Congress in Waikoloa Beach, Hawaii, April 14-18, 2013. The
      international meeting focused on the convergence of optical physics, photonics
      technology, nanoscience, and photochemistry with drug discovery and clinical
      medicine. Papers in this feature issue are representative of meeting topics,
      including advances in microscopy, nanotechnology, and optics in cancer research. 

PMID- 24575355
TI  - Measurement of the total retinal blood flow using dual beam Fourier-domain
      Doppler optical coherence tomography with orthogonal detection planes.
AB  - We present a system capable of measuring the total retinal blood flow using a
      combination of dual beam Fourier-domain Doppler optical coherence tomography with
      orthogonal detection planes and a fundus camera-based retinal vessel analyzer.
      Our results show a high degree of conformity of venous and arterial flows, which
      corroborates the validity of the measurements. In accordance with Murray's law,
      the log-log regression coefficient between vessel diameter and blood flow was
      found to be ~3. The blood's velocity scaled linearly with the vessel diameter at
      higher diameters (> 60 um), but showed a clear divergence from the linear
      dependence at lower diameters. Good agreement with literature data and the large
      range and high measurement sensitivity point to a high potential for further
      investigations. 

PMID- 24575357
TI  - Optical axial scanning in confocal microscopy using an electrically tunable lens.
AB  - This paper presents the use and characterization of an electrically focus tunable
      lens to perform axial scanning in a confocal microscope. Lateral and axial
      resolution are characterized over a >250 um axial scan range. Confocal microscopy
      using optical axial scanning is demonstrated in epithelial tissue and compared to
      traditional stage scanning. By enabling rapid axial scanning, minimizing motion
      artifacts, and reducing mechanical complexity, this technique has potential to
      enhance in vivo three-dimensional imaging in confocal endomicroscopy. 

PMID- 24575358
TI  - Applying the ResFinder and VirulenceFinder web-services for easy identification
      of acquired antibiotic resistance and E. coli virulence genes in bacteriophage
      and prophage nucleotide sequences.
AB  - Extensive research is currently being conducted on the use of bacteriophages for
      applications in human medicine, agriculture and food manufacturing. However,
      phages are important vehicles of horisontal gene transfer and play a significant
      role in bacterial evolution. As a result, concern has been raised that this
      increased use and dissemination of phages could result in spread of deleterious
      genes, e.g., antibiotic resistance and virulence genes. Meanwhile, in the wake of
      the genomic era, several tools have been developed for characterization of
      bacterial genomes. Here we describe how two of these tools, ResFinder and
      VirulenceFinder, can be used to identify acquired antibiotic resistance and
      virulence genes in phage genomes of interest. The general applicability of the
      tools is demonstrated on data sets of 1,642 phage genomes and 1,442 predicted
      prophages.

PMID- 24575359
TI  - Association of Over-Expressed Estrogen Receptor Alpha with Development of
      Tamoxifen Resistant Hyperplasia and Adenocarcinomas in Genetically Engineered
      Mice.
AB  - BACKGROUND: Estrogen receptor alpha (ERalpha) and cyclin D1 are frequently co
      expressed in human breast cancer. Some, but not all, studies link tamoxifen
      resistance to co-expression of cyclin D1 and ERalpha. In mice over-expression of
      either cyclin D1 or ERalpha in mammary epithelial cells is sufficient to induce
      mammary hyperplasia. Cyclin D1 over-expression in mice leads to mammary
      adenocarcinoma associated with activated estrogen signaling pathways. ERalpha
      over-expression in mice leads to mammary hyperplasia and cancer. Significantly,
      disease development in these mice is abrogated by loss of cyclin D1. METHODS:
      Genetically engineered mouse models were used to determine whether or not ERalpha
      over-expression demonstrated cooperativity with cyclin D1 over-expression in
      cancer development, reaction to the chemical carcinogen DMBA, or tamoxifen
      response. RESULTS: Adding ERalpha over-expression to cyclin D1 over-expression
      increased the prevalence of hyperplasia but not cancer. Single dose DMBA exposure
      did not increase cancer prevalence in any of the genotypes although cyclin D1
      over-expressing mice demonstrated a significant increase in hyperplasia.
      Tamoxifen treatment was initiated at both young and older ages to test for
      genotype-specific differences in response. Although normal ductal structures
      regressed in all genotypes at both younger and older ages, tamoxifen did not
      significantly reduce the prevalence of either hyperplasia or cancer in any of the
      genotypes. All of the cancers that developed were hormone receptor positive,
      including those that developed on tamoxifen, and all showed expression of nuclear
      localized cyclin D1. In summary, development of tamoxifen resistant hyperplasia
      and cancer was associated with expression of ERalpha and cyclin D1. CONCLUSION:
      These preclinical models will be useful to test strategies for overcoming
      tamoxifen resistance, perhaps by simultaneously targeting cell cycle regulatory
      pathways associated with cyclin D1.

PMID- 24575360
TI  - Dietary Flaxseed in Non-Small Cell Lung Cancer Patients Receiving Chemoradiation.
AB  - PURPOSE: The standard of care in Locally-Advanced Non-Small Cell Lung Cancer (LA
      NSCLC) is chemotherapy and radiation; however, Radiation-Induced Lung Injury
      (RILI), which may be prevented by the anti-inflammatory and anti-oxidant
      properties of Flaxseed (FS), impedes its maximum benefit. MATERIALS AND METHODS:
      Patients with LA-NSCLC requiring definitive RT were randomized to one FS or
      control muffin daily from start to 2 weeks after RT. Blood and urine were
      collected to quantify plasma FS metabolites, Enterodione (ED) and Enterolactone
      (EL), and urinary oxidative stress biomarkers, 8, 12-iso-iPF2a-VI (isoprostane)
      and 8-oxo-7,8-dihydro-2'deoxyguanosine (8-oxo-dGuo). Tolerability was defined as
      consuming >= 75% of the intended muffins and no >= grade 3 gastrointestinal
      toxicities. RESULTS: Fourteen patients (control,7; FS,7) were enrolled. The
      tolerability rates were 42.9 versus 71.4% (p=0.59) for FS and control,
      respectively. Mean percentages of intended number of muffins consumed were 37%
      versus 73% (p=0.12). ED and EL increased at onset of FS and decreased with
      discontinuation, confirming bioavailability. Isoprostane and 8-oxo-dGuo were
      detectable. There was a trend towards decreased rates of pneumonitis in FS.
      CONCLUSIONS: This is the first study to report FS bioavailability and quantify
      oxidative stress markers in NSCLC patients. FS in the administered muffin
      formulation did not meet tolerability criteria. Given the promising mechanism of
      FS as a radioprotectant, further investigations should focus on the optimal
      method for administration of FS.

PMID- 24575361
TI  - Synthetic Enantiopure Carbohydrate Polymers that are Highly Soluble in Water and
      Noncytotoxic.
AB  - The first synthesis of poly-amido-saccharides (PASs) from a galactose(gal)
      derived beta-lactam sugar monomer is reported. The polymers are prepared using a
      controlled anionic ring-opening polymerization and characterized by NMR, optical
      rotation, IR, and GPC. Galactose-derived PASs display high solubility in aqueous
      solutions and are noncytotoxic to HepG2, CHO, and HeLa cell lines. To evaluate
      whether gal-derived PASs are recognized by the gal-specific lectin present on
      human hepatocytes, cellular uptake of rhodamine-labeled polymers is assessed
      using flow cytometry and fluorescence microscopy. Based on these results, the
      polymers are taken into cells via endocytosis that is not dependent on the gal
      specific receptor on hepatocytes. Neutral, hydrophilic polymers, such as gal
      derived PASs, are desirable materials for a range of biomedical applications,
      such as drug delivery, surface passivation, and hydrogel formation.

PMID- 24575362
TI  - In this issue of Adipocyte.

PMID- 24575363
TI  - The origin and definition of brite versus white and classical brown adipocytes.
AB  - White adipose tissue stores energy while brown adipose tissue contributes to body
      temperature maintenance through non-shivering thermogenesis. In addition, brite
      (brown-in-white) adipocytes resembling classical brown adipocytes within
      predominantly white adipose tissue can be found in response to cold adaptation or
      other stimuli. Even though our understanding of brite adipocyte formation has
      increased substantially in the last few years, it is still unclear how brite and
      classical brown adipocytes are formed in vivo. In this review, we outline and
      discuss the current understanding of brite adipocyte nomenclature, developmental
      origin and possible mechanisms of their recruitment. We reason that future work
      in the field will bridge in vivo tracing studies and primary cell
      characterization with molecular mechanistic data from in vitro approaches to
      devise new means to increase energy expenditure. 

PMID- 24575364
TI  - Is the lack of adiponectin associated with increased ER/SR stress and
      inflammation in the heart?
AB  - Objective To study whether there is an association between adiponectin and
      endoplasmic reticulum/sarcoplasmic reticulum (ERSR) stress. Research design
      Eleven-month-old male wild-type (WT) and adiponectin knockout (ADKO) mice were
      placed on chow or high fat diet for 12 weeks. The changes in ER stress and
      inflammatory genes were determined in the epididymal adipose, as well as heart
      tissue of adult WT and ADKO mice. To understand the role of ER/SR stress in the
      regulation of adiponectin, we studied the effect of tunicamycin or palmitate on
      H9C2 cardiomyoblasts in culture. To demonstrate the protective role of
      adiponectin, we studied the effect of purified adiponectin on the regulation of
      ERSR stress genes and inflammation in H9C2 cardiomyoblasts. Results (1) High fat
      diet increased TNFalpha in adipose tissue of ADKO mice. (2) ERSR stress genes,
      HSPa5, ERN1, and GADD34, and inflammation response genes, TNFalpha and CD68, were
      increased in heart of ADKO mice. High fat diet did not further increase the
      effect. (3) Induction of ERSR stress by tunicamycin in H9C2 resulted in the
      upregulation of ERSR stress response genes along with downregulation of
      adiponectin, adiponectin receptors 1 and 2, and Serca2A. ER stress was
      accompanied by down regulation of Ikbetaalpha and an increase in HSPa5 proteins.
      (4) Adiponectin decreased ERSR stress and inflammation response genes and
      increased Serca2A in to H9C2 cardiomyoblasts. Conclusion The lack of adiponectin
      is associated with increased ER/SR stress and inflammation in the heart.
      Adiponectin provides a protective effect by lowering inflammation and ER/SR
      stress along with increasing Serca2A in H9C2 cells. 

PMID- 24575366
TI  - Energy balance-dependent regulation of ovine glucose 6-phosphate dehydrogenase
      protein isoform expression.
AB  - G6PDH is the rate-limiting enzyme of the pentose phosphate pathway and one of the
      principal source of NADPH, a major cellular reductant. Importantly, in ruminant's
      metabolism the aforementioned NADPH provided, is utilized for de novo fatty acid
      synthesis. Previous work of cloning the ovine (Ovis aries) og6pdh gene has
      revealed the presence of two cDNA transcripts (og6pda and og6pdb), og6pdb being a
      product of alternative splicing not similar to any other previously reported.(1)
      In the current study the effect of energy balance in the ovine G6PDH protein
      expression was investigated, shedding light on the biochemical features and
      potential physiological role of the oG6PDB isoform. Changes in energy balance
      leads to protein expression changes in both transcripts, to the opposite
      direction and not in a proportional way. Negative energy balance was not in favor
      of the presence of any particular isoform, while both protein expression levels
      were not significantly different (P > 0.05). In contrast, at the transition point
      from negative to positive and on the positive energy balance, there is a
      significant increase of oG6PDA compared with oG6PDB protein expression (P <
      0.001). Both oG6PDH protein isoforms changed significantly toward the positive
      energy balance. oG6PDA is escalating, while oG6PDB is falling, under the same
      stimulus (positive energy balance alteration). This change is also positively
      associated with increasing levels in enzyme activity, 4 weeks post-weaning in
      ewes' adipose tissue. Furthermore, regression analysis clearly demonstrated the
      linear correlation of both proteins in response to the WPW, while energy balance,
      enzyme activity, and oG6PDA relative protein expression follow the same
      escalating trend; in contrast, oG6PDB relative protein expression falls in time,
      similar to both transcripts accumulation pattern, as reported previously.(2.) 

PMID- 24575365
TI  - Impairment of insulin-stimulated glucose transport and ERK activation by
      adipocyte-specific knockout of PKC-lambda produces a phenotype characterized by
      diminished adiposity and enhanced insulin suppression of hepatic gluconeogenesis.
AB  - Tissue-specific knockout (KO) of atypical protein kinase C-lambda (PKC-lambda)
      impairs insulin-stimulated glucose transport in muscle (M) and lipid synthesis in
      liver (L), thereby producing insulin resistance in MlambdaKO mice and insulin
      hypersensitivity in LlambdaKO mice. Here, we generated mice with KO of PKC-lambda
      in adipocytes, i.e., AlambdaKO mice. In isolated adipocytes of AlambdaKO mice,
      insulin-stimulated aPKC activity and glucose transport were diminished, as were
      ERK levels and activity. Insulin-stimulated glucose transport and insulin
      activation of ERK in adipocytes of wild-type mice were similarly inhibited by
      acute inhibition of PKC-lambda with a highly-specific chemical inhibitor. With
      impairments in glucose transport and ERK activation, AlambdaKO mice had
      diminished adiposity and serum leptin levels. In addition, AlambdaKO mice had
      normal glucose tolerance and insulin hypersensitivity owing to enhanced
      suppression of hepatic glucose output, which apparently reflected increases in
      Akt activity and FoxO1 phosphorylation, and subsequent decreases in expression of
      gluconeogenic phosphoenolpyruvate carboxykinase. We conclude that: PKC-lambda is
      required for insulin-stimulated glucose transport and ERK signaling in mouse
      adipocytes; and diminution of these processes is attended by leanness and
      therefore hypoleptinemia. How these and perhaps other PKC-lambda-dependent
      processes communicate to liver and improve insulin suppression of hepatic
      gluconeogenesis remains unclear. 

PMID- 24575368
TI  - FGF receptor antagonism does not affect adipose tissue development in
      nutritionally induced obesity.
AB  - The fibroblast growth factor (FGF)-FGF receptor (FGFR) system plays a role in
      angiogenesis and maintenance of vascular integrity, but its potential role in
      adipose tissue related angiogenesis and development is still unknown.
      Administration of SSR, a low molecular weight inhibitor of multiple FGFRs, did
      not significantly affect body weight nor weight of subcutaneous or gonadal (GON)
      fat, as compared with pair-fed control mice. Adipocyte hypertrophy and reduced
      adipocyte density were only observed in GON adipose tissues of treated mice.
      Adipose tissue angiogenesis was not affected by SSR treatment, as normalized
      blood vessel density was comparable in adipose tissues of both groups. Blocking
      the FGF-FGFR system in vivo does not markedly affect adipose tissue development
      in mice with nutritionally induced obesity. 

PMID- 24575367
TI  - Adiponectin and IL-6: Mediators of inflammation in progression of healthy to type
      2 diabetes in Indian population.
AB  - Aim The objective of the study was to identify the association if any, of
      inflammatory markers (adiponectin and IL-6) with fasting glucose in normoglycemic
      (healthy), prediabetic (impaired fasting glucose), and hyperglycemic (diabetic)
      people in Indian population. Methods Total 162 volunteers were distributed into 3
      groups (normoglycemic, individuals with impaired fasting glucose, and
      hyperglycemic) as per ADA criterion. The blood chemistry parameters were analyzed
      and serum adiponectin and IL-6 levels were measured by ELISA. Results Significant
      reduction was observed in serum adiponectin level in hyperglycemic and impaired
      fasting glucose population compared with normoglycemic population. Significant
      reduction in adiponectin was also observed in impaired fasting glucose group
      compared with hyperglycemic group. Similarly significant increase was also
      observed in IL-6 level in hyperglycemic and impaired fasting glucose groups
      compared with normoglycemic group. Conclusions From our data it can be summarized
      that there is a significant change in both adiponectin (reduction) and IL-6
      (increase) levels in normoglycemic (healthy), prediabetic (impaired fasting
      glucose), and hyperglycemic (diabetic) population in Indian population. There is
      a significant but gradual change during the progression of healthy toward
      diabetic population via pre-diabetic condition. 

PMID- 24575369
TI  - Gelatinase B (MMP-9) gene silencing does not affect murine preadipocyte
      differentiation.
AB  - Growth of adipose tissue involves differentiation of preadipocytes into mature
      lipid-containing adipocytes. The matrix metalloproteinases (MMPs) are known
      regulators of adipose tissue biology, and previous studies suggested a key role
      for gelatinase B (MMP-9) in adipogenesis. In the present study we have evaluated
      a potential functional role of MMP-9 by performing gene silencing in 3T3-F442A
      preadipocytes. At the end of a 12-day differentiation period, no significant
      differences were observed between MMP-9 knockdown cells and the control cells
      with respect to intracytoplasmatic lipid content, or expression of the adipogenic
      markers aP2, PPARgamma, Lpl, and adiponectin, or of the preadipocyte marker Pref
      1. Thus, in vitro differentiation of 3T3-F442A preadipocytes into mature
      adipocytes is not significantly affected by the loss of MMP-9. 

PMID- 24575370
TI  - Novel nuances of human brown fat.
AB  - There is a current debate in the literature on whether human fat derived from the
      supraclavicular region should be classified as brown, or as the white fat-derived
      less potent, brite/beige. This commentary addresses whether the existing
      classification defined in mice is sufficient to describe the types of thermogenic
      adipocytes in humans. We recently published a contradictory mRNA expression
      signature of human supraclavicular fat defined by an upregulation of the brite
      marker TBX1 along with the classical brown markers ZIC1 and LHX8, as well as
      genes indicating brown fat activity including UCP1, PGC-1alpha, and PRDM16; and,
      finally, a downregulation of the white/brite markers HOXC8 and HOXC9.
      Subcutaneous fat was used as reference material. Another recent study presents a
      higher expression of ZIC1 and a lower expression of TBX1 in interscapular
      compared with supraclavicular fat. Here, however, there was no difference in
      UCP1, PGC-1alpha, PRDM16, suggesting both depots had equal brown fat potency.
      Taken together, supraclavicular brown fat derived from adult humans seems to
      represent a type of brown fat with distinct features from both subcutaneous
      white/brite and interscapular brown fat. Therefore, the classification of
      adipocyte subtypes defined in mice may need reconsideration when applying to
      humans. 

PMID- 24575371
TI  - The immune cell transcription factor T-bet: A novel metabolic regulator.
AB  - Obesity-associated insulin resistance is accompanied by an alteration in the
      Th1/Th2 balance in adipose tissue. T-bet (Tbx21) is an immune cell transcription
      factor originally described as the master regulator of Th1 cell development,
      although is now recognized to have a role in both the adaptive and innate immune
      systems. T-bet also directs T-cell homing to pro-inflammatory sites by the
      regulation of CXCR3 expression. T-bet(-/-) mice have increased visceral adiposity
      but are more insulin-sensitive, exhibiting reduced immune cell content and
      cytokine secretion specifically in the visceral fat depot, perhaps due to altered
      T-cell trafficking. Studies of T-bet deficiency on Rag2-- and IFN-gamma-deficient
      backgrounds indicate the importance of CD4(+) T cells and IFN-gamma in this
      model. This favorable metabolic phenotype, uncoupling adiposity from insulin
      resistance, is present in young lean mice yet persists with age and increasing
      obesity. We suggest a novel role for T-bet in metabolic regulation. 

PMID- 24575373
TI  - The p38-PGC-1alpha-irisin-betatrophin axis: Exploring new pathways in insulin
      resistance.
AB  - The discovery of irisin as a novel and promising peptidic hormone has raised
      hopes regarding the hypothesis that irisin may provide additional benefits, not
      only for obesity and diabetes, but also for a wide range of pathological
      conditions since this hormone may prove to be therapeutically and clinically
      beneficial. In addition, a new hormone, betatrophin, has recently been identified
      by Yi and coworkers. Both hormones are connected by a new pathway clearly
      involved in insulin resistance. We hypothesize here how these hormones may be
      linked and their possible implications in both aged-reduced restricted
      regenerative capacity and dedifferentiated beta cells of diabetic patients. 

PMID- 24575372
TI  - Two types of brown adipose tissue in humans.
AB  - During the last years the existence of metabolically active brown adipose tissue
      in adult humans has been widely accepted by the research community. Its unique
      ability to dissipate chemical energy stored in triglycerides as heat makes it an
      attractive target for new drugs against obesity and its related diseases. Hence
      the tissue is now subject to intense research, the hypothesis being that an
      expansion and/or activation of the tissue is associated with a healthy metabolic
      phenotype. Animal studies provide evidence for the existence of at least two
      types of brown adipocytes. Apart from the classical brown adipocyte that is found
      primarily in the interscapular region where it constitutes a thermogenic organ, a
      second type of brown adipocyte, the so-called beige adipocyte, can appear within
      white adipose tissue depots. The fact that the two cell types develop from
      different precursors suggests that they might be recruited and stimulated by
      different cues and therefore represent two distinct targets for therapeutic
      intervention. The aim of this commentary is to discuss recent work addressing the
      question whether also humans possess two types of brown adipocytes and to
      highlight some issues when looking for molecular markers for such cells. 

PMID- 24575374
TI  - The multifaceted role of profilin-1 in adipose tissue inflammation and glucose
      homeostasis.
AB  - Profilin-1 (pfn) is a small ubiquitous protein that can bind to: (1) G-actin, (2)
      phosphatidylinositol 4,5-bisphosphate, and (3) a heterogeneous group of proteins
      harboring poly-l-proline stretches. Through these interactions, pfn integrates
      signaling from a diverse array of extracellular cues with actin cytoskeleton
      dynamics. Cumulating evidence indicates that changes in pfn levels are associated
      and may play a pathogenic role in such inflammatory diseases as atherosclerosis
      and glomerulonephritis. We recently demonstrated that high fat diet (HFD)
      increases pfn expression in the white adipose tissue (WAT), but not in the liver
      or the muscle. Pfn heterozygote mice (PfnHet) were protected against HFD-induced
      glucose intolerance, and WAT and systemic inflammation, when compared to pfn wild
      type mice. In addition to blunted accumulation of macrophages and reduced "pro
      inflammatory" cytokines, the WAT of PfnHet exhibited preserved frequency of
      regulatory T cells. These findings suggest that pfn levels in WAT-both adipocytes
      and hematopoietic-derived cells-can modulate immune homeostasis within the WAT
      and glucose tolerance systemically. Here, we review the interaction of pfn with
      his diverse array of binding partners and discuss mechanisms that may underlie
      the effects of pfn dosage on insulin sensitivity and metabolic inflammation. 

PMID- 24575375
TI  - Adipose tissue oxygenation: Effects on metabolic function.
AB  - With the increasing prevalence of obesity there is a concomitant increase in
      white adipose tissue dysfunction, with the tissue moving toward a proinflammatory
      phenotype. Adipose tissue hypoxia has been proposed as a key underlying mechanism
      triggering tissue dysfunction but data from human, in vivo studies, to support
      this hypothesis is limited. Human adipose tissue oxygenation has been
      investigated by direct assessment of tissue oxygen tension (pO2) or by expression
      of hypoxia-sensitive genes/protein in lean and obese subjects but findings are
      inconsistent. An obvious read-out of hypoxia is the effect on intermediary
      metabolism, and we have investigated the functional consequences, in terms of a
      "metabolic signature" of human adipose tissue hypoxia in vivo. Here, we discuss
      the different approaches used and the importance of integrative physiological
      techniques to try and elucidate what defines adipose tissue hypoxia in humans. 

PMID- 24575376
TI  - The role of thrombospondin (TSP)-1 in obesity and diabetes.
AB  - Matricellular proteins are extracellular macromolecules that do not serve a
      structural role, but when incorporated into the matrix, modulate cell:cell and
      cell:matrix interactions. The matricellular protein thrombospondin (TSP)-1, a
      potent angiostatic mediator and activator of transforming growth factor (TGF)
      beta, is upregulated in diabetes and obesity and may be involved in the
      pathogenesis of metabolic dysregulation and organ dysfunction. This manuscript
      discusses recently published observations on the role of TSP-1 in metabolic
      disease. In obesity models induced by a high-fat diet, adipose tissue TSP-1
      upregulation induces inflammation and promotes weight gain and metabolic
      dysfunction. TSP-1 may have direct effects on adipocyte proliferation and fatty
      acid uptake. In diabetic subjects, TSP-1 upregulation in kidney, myocardium, and
      vascular tissue may promote dysfunction. In the myocardium, TSP-1 upregulation
      may transduce angiostatic signals inducing vascular rarefaction. Dissection of
      the functional domains involved in TSP-1 actions may lead to the development of
      peptide-based strategies for treatment of diabetes and its complications. 

PMID- 24575377
TI  - A2A blockade enhances anti-metastatic immune responses.
AB  - The specific targeting of tumor-elicited immunosuppression is a promising
      strategy for the treatment of cancer. We have recently demonstrated that
      targeting the immunosuppressive pathway mediated by CD73-derived adenosine
      through the blockade of A2A/A2B adenosine receptors significantly reduced the
      metastatic potential of CD73+ breast carcinomas and melanomas via both
      immunological and non-immunological mechanisms.

PMID- 24575378
TI  - Disarmed by density: A glycolytic break for immunostimulatory dendritic cells?
AB  - We observed a cell concentration-dependent differentiation switch among cultured
      dendritic cells (DCs) triggered by lactic acid, a product of glycolytic
      metabolism. In particular, while interleukin (IL)-12, IL-23, and tumor necrosis
      factor alpha (TNFalpha)-producing, migratory DCs developed in sparse cultures, IL
      10-producing, non-migratory DCs differentiated in dense cultures. This points to
      a novel opportunity for tailoring DC-based anticancer therapies through
      metabolism modulation in developing DCs.

PMID- 24575380
TI  - Invariant NKT cells: Killers and conspirators against cancer.
AB  - Although invariant natural killer T (iNKT) cells influence antitumor responses
      indirectly by secreting cytokines and promoting the cytolytic functions of T and
      NK cells, we find that iNKT cells mediate direct tumoricidal activity in vitro
      and significantly inhibit tumor growth in vivo, even in the absence of other
      cytotoxic lymphocytes.

PMID- 24575381
TI  - Interferon alpha interferes with immunological tolerance.
AB  - The ability of regulatory T cells (Tregs) to promote immunological tolerance
      represents an important obstacle in cancer immunotherapy. We have recently
      discovered that the clinically established immunotherapeutic agent interferon
      alpha (IFNalpha) inactivates the suppressive functions of human Tregs. Here, we
      outline the mechanisms whereby IFNalpha mediates this important function and
      discuss its therapeutic implications for cancer immunotherapy.

PMID- 24575382
TI  - Combining NK cells and mAb9.2.27 to combat NG2-dependent and anti-inflammatory
      signals in glioblastoma.
AB  - Glioblastoma is a deadly brain cancer with limited treatment options. Targeting
      chondroitin sulfate proteoglycan 4 (CSPG4, best known as NG2) with the monoclonal
      antibody mAb9.2.27 and activated natural killer (NK) cells abrogated the tumor
      growth and prolonged the survival of glioblastoma-bearing animals by favoring the
      establishment of a pro-inflammatory microenvironment. The combination of NK cells
      and mAb9.2.27 recruited ED1+CCR2low macrophages that stimulated
      ED1+ED2lowMHCIIhigh microglial cells to exert robust cytotoxicity. Our findings
      demonstrate the therapeutic potential of targeting salient tumor associated
      antigens.

PMID- 24575383
TI  - Immunovirotherapy for the treatment of glioblastoma.
AB  - We have recently described a new murine model of glioblastoma, generated by the
      implantation of syngeneic glioblastoma stem cells into immunocompetent mice, that
      recapitulates the salient histopathological and immunological features of the
      human disease. We employed this model to demonstrate the multifaceted activity of
      an oncolytic herpes simplex virus genetically modified to express interleukin-12,
      G47?-IL12.

PMID- 24575384
TI  - An immunotherapeutic intervention against tumor progression: Targeting a driver
      of the epithelial-to-mesenchymal transition.
AB  - Targeting the epithelial-to-mesenchymal transition (EMT) is emerging as a novel
      intervention against tumor progression and metastatic dissemination, as well as
      the resistance to chemo- and radiotherapy displayed by multiple carcinomas. We
      have recently developed an immunotherapeutic approach to target a major driver of
      EMT, the T-box transcription factor T (also known as brachyury). This therapeutic
      paradigm is currently being tested in patients with advanced carcinomas in the
      context of a Phase I clinical trial.

PMID- 24575379
TI  - Immunosuppressants in cancer prevention and therapy.
AB  - Rapalogs such as rapamycin (sirolimus), everolimus, temserolimus, and deforolimus
      are indicated for the treatment of some malignancies. Rapamycin is the most
      effective cancer-preventive agent currently known, at least in mice, dramatically
      delaying carcinogenesis in both normal and cancer-prone murine strains. In
      addition, rapamycin and everolimus decrease the risk of cancer in patients
      receiving these drugs in the context of immunosuppressive regimens. In general,
      the main concern about the use of immunosuppressants in humans is an increased
      risk of cancer. Given that rapalogs are useful in cancer prevention and therapy,
      should they be viewed as immunosuppressants or immunostimulators? Or should we
      reconsider the role of immunity in cancer altogether? In addition to its anti
      viral, anti-inflammatory, anti-angiogenic and anti-proliferative effects,
      rapamycin operates as a gerosuppressant, meaning that it inhibits the cellular
      conversion to a senescent state (the so-called geroconversion), a fundamental
      process involved in aging and age-related pathologies including cancer.

PMID- 24575385
TI  - The immune response in HPV+ oropharyngeal cancer.
AB  - Although human papillomavirus (HPV)+ oropharyngeal cancers often present with
      metastasis, most patients have excellent long-term survival. The reason
      underlying such an apparent contradiction remains unclear, but we have recently
      demonstrated that the improved survival of HPV+ oropharyngeal cancer patients has
      an immunological component, as the levels of tumor-infiltrating lymphocytes
      (TILs) can be used to stratify HPV+ patients into high-risk and low-risk groups.

PMID- 24575386
TI  - Immunotherapeutic implications of the immunophenotype of pediatric brain tumors.
AB  - The cytofluorometric analysis of dissociated tumor samples identified distinct
      immunophenotypes among the most common variants of pediatric brain tumor. These
      findings suggest that immunotherapeutic regimens against pediatric brain
      malignancies should be tailored to individual tumor types.

PMID- 24575387
TI  - Growth Impairment of Small-Cell Cancer by Targeting Pro-Vasopressin with MAG-1
      Antibody.
AB  - Previously we demonstrated that human small-cell lung cancer (SCLC) seems to
      universally express the vasopressin gene, and this leads to the presence of a
      cell surface marker representing the entire pro-hormone precursor. In this study,
      we show this marker can be targeted with MAG-1, a mouse monoclonal antibody
      against a C-terminal moiety on pro-vasopressin. In vitro targeting of cell lines
      derived from primary and recurrent disease demonstrates attachment of antibody to
      the cell surface followed by internalization. In vivo targeting with (99)Tc
      labeled Fab fragments of MAG-1 shows selective attachment to xenografts. In vivo
      treatment of tumors from classical cell line, NCI H345, with either ~1.65 mCi
      (~1.65 mg)/kg body weight (BW) of (90)Yttrium-labeled MAG-1, or ~1.65 mg/kg BW
      native MAG-1, delivered every second day for 6 days produced similar reductions
      in the growth rate to ~50% (p < 0.03). When dosing with native MAG-1 was
      escalated to daily amounts of ~3.3 mg/kg BW over 16 days, tumor growth rates fell
      to ~33% of saline controls (p < 0.005). Examination of tumors treated with this
      higher dosing demonstrated the presence in several of extensive apoptosis. Normal
      tissues seemed to be unaffected. A larger dosage of MAG-1 (~6.6 mg/kg BW) given
      daily for 14 days was used to treat xenografts of the variant cell line NCI H82
      representing recurrent disease. This treatment decreased the rate of increase in
      tumor size by half, and doubling time ~3-fold. Increases in cleaved PARP
      supported increased apoptosis with antibody treatment. We believe these data
      provide evidence that the growth rate of SCLC tumors can be extensively reduced
      by treatment with MAG-1 antibody, and that a humanized form of this antibody
      could, in future, be potentially used for targeting therapy onto recurrent SCLC
      in patients. 

PMID- 24575389
TI  - Prophylactic bilateral salpingectomy as a prevention strategy in women at high
      risk of ovarian cancer: a mini-review.
AB  - Risk-reducing bilateral salpingo-oophorectomy is a proven strategy to reduce the
      risk of serous ovarian cancer associated with germline BRCA mutations. It is most
      effective when performed before natural menopause, but it will render a woman
      prematurely menopausal. The tubal hypothesis of serous ovarian cancer brings with
      it the possibility of the alternative surgical approach in younger women
      comprising of risk-reducing bilateral salpingectomy while conserving their
      ovaries until nearer the age of natural menopause, when a delayed bilateral
      oophorectomy can be performed. This article will review the evidence behind the
      tubal hypothesis of serous ovarian cancer and explore the opportunities for
      translating this into clinical cancer prevention practice. 

PMID- 24575390
TI  - A Dialog on the First 20 Years of PML Research and the Next 20 Ahead.
AB  - This introductory article has been written in the form of a conversation between
      Pier Paolo Pandolfi, Director of the Cancer Center of Beth Israel Deaconess
      Medical Center in Boston, and Rosa Bernardi, a former post-doctoral fellow in the
      laboratory of Dr. Pandolfi, now principal investigator at San Raffaele Scientific
      Institute in Milan, Italy. We have chosen this atypical review format because we
      want to offer to our readers a more direct and personal perspective on the first
      20 years of research over the promyelocytic leukemia gene. This article begins as
      an interview, but soon transforms into a dialog where we exchange our thoughts on
      a number of issues around the past, present, and future research over the biology
      of PML. We were particularly keen on emphasizing the aspects that we find most
      interesting or challenging, therefore, we warn our readers that this will not be
      a comprehensive essay but rather a very personal view of what has been, is, and
      will be exciting and interesting in the PML world, in our opinion. 

PMID- 24575388
TI  - The Possible Effects on Socio-Economic Inequalities of Introducing HPV Testing as
      Primary Test in Cervical Cancer Screening Programs.
AB  - BACKGROUND: Screening with HPV is more effective than Pap test in preventing
      cervical cancer. HPV as primary test will imply longer intervals and a triage
      test for HPV positive women. It will also permit the development of self-sampling
      devices. These innovations may affect population coverage, participation, and
      compliance to protocols, and likely in a different way for less educated, poorer,
      and disadvantaged women. AIM: To describe the impact on inequalities, actual or
      presumed, of the introduction of HPV-based screening. METHODS: The putative HPV
      based screening algorithm has been analyzed to identify critical points for
      inequalities. A systematic review of the literature has been conducted searching
      PubMed on HPV screening coverage, participation, and compliance. RESULTS were
      summarized in a narrative synthesis. RESULTS: Knowledge about HPV and cervical
      cancer was lower in women with low socio-economic status and in disadvantaged
      groups. A correct communication can reduce differences. Longer intervals will
      make it easier to achieve high-population coverage, but higher cost of the test
      in private providers could reduce the use of opportunistic screening by
      disadvantaged women. There are some evidences that inviting for HPV test instead
      of Pap increases participation, but there are no data on social differences. Self
      sampling devices are effective in increasing participation and coverage. Some
      studies showed that the acceptability of self-sampling is higher in more educated
      women, but there is also an effect on hard-to-reach women. Communication of HPV
      positivity may increase anxiety and impact on sexual behaviors, the effect is
      stronger in low educated and disadvantaged women. Finally, many studies found
      indirect evidence that unvaccinated women are or will be more probably under
      screened. CONCLUSION: The introduction of HPV test may increase population
      coverage, but non-compliance to protocols and interaction with opportunistic
      screening can increase the existing inequalities.

PMID- 24575392
TI  - Listeria monocytogenes virulence factor secretion: don't leave the cell without a
      chaperone.
AB  - In Gram-positive bacteria, the secretion of proteins requires translocation of
      polypeptides across the bacterial membrane into the highly charged environment of
      the membrane-cell wall interface. Here, proteins must be folded and often further
      delivered across the matrix of the cell wall. While many aspects of protein
      secretion have been well studied in Gram-negative bacteria which possess both an
      inner and outer membrane, generally less attention has been given to the
      mechanics of protein secretion across the single cell membrane of Gram-positive
      bacteria. In this review, we focus on the role of a post-translocation secretion
      chaperone in Listeria monocytogenes known as PrsA2, and compare what is known
      regarding PrsA2 with PrsA homologs in other Gram-positive bacteria. PrsA2 is a
      member of a family of membrane-associated lipoproteins that contribute to the
      folding and stability of secreted proteins as they cross the bacterial membrane.
      PrsA2 contributes to the integrity of the L. monocytogenes cell wall as well as
      swimming motility and bacterial resistance to osmotic stress; however its most
      critical role may be its requirement for L. monocytogenes virulence and viability
      within host cells. A better understanding of the role of PrsA2 and PrsA-like
      homologs will provide insight into the dynamics of protein folding and stability
      in Gram-positive bacteria and may result in new strategies for optimizing protein
      secretion as well as inhibiting the production of virulence factors. 

PMID- 24575391
TI  - Nutrient salvaging and metabolism by the intracellular pathogen Legionella
      pneumophila.
AB  - The Gram-negative bacterium Legionella pneumophila is ubiquitous in freshwater
      environments as a free-swimming organism, resident of biofilms, or parasite of
      protozoa. If the bacterium is aerosolized and inhaled by a susceptible human
      host, it can infect alveolar macrophages and cause a severe pneumonia known as
      Legionnaires' disease. A sophisticated cell differentiation program equips L.
      pneumophila to persist in both extracellular and intracellular niches. During its
      life cycle, L. pneumophila alternates between at least two distinct forms: a
      transmissive form equipped to infect host cells and evade lysosomal degradation,
      and a replicative form that multiplies within a phagosomal compartment that it
      has retooled to its advantage. The efficient changeover between transmissive and
      replicative states is fundamental to L. pneumophila's fitness as an intracellular
      pathogen. The transmission and replication programs of L. pneumophila are
      governed by a number of metabolic cues that signal whether conditions are
      favorable for replication or instead trigger escape from a spent host. Several
      lines of experimental evidence gathered over the past decade establish strong
      links between metabolism, cellular differentiation, and virulence of L.
      pneumophila. Herein, we focus on current knowledge of the metabolic components
      employed by intracellular L. pneumophila for cell differentiation, nutrient
      salvaging and utilization of host factors. Specifically, we highlight the
      metabolic cues that are coupled to bacterial differentiation, nutrient
      acquisition systems, and the strategies utilized by L. pneumophila to exploit
      host metabolites for intracellular replication. 

PMID- 24575393
TI  - Animal models for oral transmission of Listeria monocytogenes.
AB  - Listeria monocytogenes has been recognized as a food borne pathogen in humans
      since the 1980s, but we still understand very little about oral transmission of
      L. monocytogenes or the host factors that determine susceptibility to
      gastrointestinal infection, due to the lack of an appropriate small animal model
      of oral listeriosis. Early feeding trials suggested that many animals were highly
      resistant to oral infection, and the more reproducible intravenous or
      intraperitoneal routes of inoculation soon came to be favored. There are a fair
      number of previously published studies using an oral infection route, but the
      work varies widely in terms of bacterial strain choice, the methods used for oral
      transmission, and various manipulations used to enhance infectivity. This mini
      review summarizes the published literature using oral routes of L. monocytogenes
      infection and highlights recent technological advances that make oral infection a
      more attractive model system. 

PMID- 24575397
TI  - Health supplement consumption behavior in the older adult population: an
      exploratory study.
AB  - Health supplement consumption behavior is important to maintain health status.
      The purpose of the study was to explore the spending pattern on health supplement
      consumption behavior in Hong Kong older adults population. The present study was
      a cross-sectional survey study; and was collected from via a street-intercept
      interview. Participants were approached and invited to response to a
      questionnaire. The location for data collection was evenly distributed in Hong
      Kong, Kowloon, and New Territories. The questionnaire included demographic data
      and source of income source, spending habits on health supplement products, and
      whether they performed regular health check. There were 982 participants
      interviewed; and 46% was male and 54% was female. The participants are divided
      into young-old (age 50-69) and old-old group (age 70 or above). The mean age is
      67.93 +/- 10.386. Most of the participants have regular body check; the major
      reason is to maintain health. Less than half of the participants spent money on
      health supplement products; the major reason for such purchase was to maintain
      health; while for not buying is, they did not think that would have any effect in
      their health. Also, more young-old participants have regular body check and spend
      more money on health supplement products; while old-old group participants were
      less likely to concern their health, and they were less likely to perform regular
      body check and purchase health supplement products. The present research reveals
      the pattern of the health supplement consumption behavior of young-old and old
      old. Young-old group and old-old group have difference pattern according to their
      difference age-related health condition and the amount of spare money. Different
      educational program concern health consciousness and promotion strategy of
      regular body check and health supplement products need be tailor-made for older
      adults, and for young-old and old-old groups. 

PMID- 24575395
TI  - The evolution of bladder augmentation: from creating a reservoir to
      reconstituting an organ.
AB  - Bladder augmentation was first described in 1899. The goal at the time was to
      establish the ideal method to create a simple capacious reservoir for the safe
      storage of urine. That simple idea has over the last 100 years grown into one of
      the most dynamic areas in Pediatric Urology. Creative minds and hands from
      individuals in multiple disciplines have led us from creating a reservoir to the
      threshold of recreating a functional organ. In this review, we look at the
      historical evolution of bladder augmentation and how it exponentially grew in
      scope from those initial descriptions of intestinocystoplasty to the work being
      reported today in the field of tissue engineering. 

PMID- 24575396
TI  - Bullying behaviors in children and adolescents: "an ongoing story".
AB  - Bullying in school-aged children is a universal problem, which continues to be a
      serious threat to physical and emotional health of children and adolescents. This
      article highlights the prevalence, the common characteristics of bullies and
      victims, as well as the short- and long-term impact of bullying involvement. Key
      areas highlighted include the efficacy of bullying prevention programs, which can
      help health care providers to assess and provide interventions to children and
      adolescents affected by bullying. 

PMID- 24575394
TI  - Obstetric Pharmacokinetic Dosing Studies are Urgently Needed.
AB  - Use of pharmacotherapy during pregnancy is common and increasing. Physiologic
      changes during pregnancy may significantly alter the overall systemic drug
      exposure, necessitating dose changes. A search of PubMed for pharmacokinetic
      clinical trials showed 494 publications during pregnancy out of 35,921 total
      pharmacokinetic published studies (1.29%), from the late 1960s through August 31,
      2013. Closer examination of pharmacokinetic studies in pregnant women published
      since 2008 (81 studies) revealed that about a third of the trials were for
      treatment of acute labor and delivery issues, a third included studies of
      infectious disease treatment during pregnancy, and the remaining third were for
      varied ante-partum indications. Approximately, two-thirds of these recent studies
      were primarily funded by government agencies worldwide, one-quarter were
      supported by private non-profit foundations or combinations of government and
      private funding, and slightly <10% were supported by pharmaceutical industry. As
      highlighted in this review, vast gaps exist in pharmacology information and
      evidence for appropriate dosing of medications in pregnant women. This lack of
      knowledge and understanding of drug disposition throughout pregnancy place both
      the mother and the fetus at risk for avoidable therapeutic misadventures -
      suboptimal efficacy or excess toxicity - with medication use in pregnancy.
      Increased efforts to perform and support obstetric dosing and pharmacokinetic
      studies are greatly needed. 

PMID- 24575398
TI  - Do personally tailored videos in a web-based physical activity intervention lead
      to higher attention and recall? - an eye-tracking study.
AB  - Over half of the Australian population does not meet physical activity guidelines
      and has an increased risk of chronic disease. Web-based physical activity
      interventions have the potential to reach large numbers of the population at low
      cost, however issues have been identified with usage and participant retention.
      Personalized (computer-tailored) physical activity advice delivered through video
      has the potential to address low engagement, however it is unclear whether it is
      more effective in engaging participants when compared to text-delivered
      personalized advice. This study compared the attention and recall outcomes of
      tailored physical activity advice in video- vs. text-format. Participants (n =
      41) were randomly assigned to receive either video- or text-tailored feedback
      with identical content. Outcome measures included attention to the feedback,
      measured through advanced eye-tracking technology (TobiiX 120), and recall of the
      advice, measured through a post intervention interview. Between group ANOVA's,
      Mann-Whitney U tests and chi square analyses were applied. Participants in the
      video-group displayed greater attention to the physical activity feedback in
      terms of gaze-duration on the feedback (7.7 vs. 3.6 min, p < 001), total fixation
      duration on the feedback (6.0 vs. 3.3 min, p < 001), and focusing on feedback
      (6.8 vs. 3.5 min, p < 001). Despite both groups having the same ability to
      navigate through the feedback, the video-group completed a significantly (p <
      0.001) higher percentage of feedback sections (95%) compared to the text-group
      (66%). The main messages were recalled in both groups, but many details were
      forgotten. No significant between group differences were found for message
      recall. These results suggest that video-tailored feedback leads to greater
      attention compared to text-tailored feedback. More research is needed to
      determine how message recall can be improved, and whether video-tailored advice
      can lead to greater health behavior change. 

PMID- 24575401
TI  - Antimicrobial activity of artemisinin and precursor derived from in vitro
      plantlets of Artemisia annua L.
AB  - Artemisia annua L., a medicinal herb, produces secondary metabolites with
      antimicrobial property. In Malaysia due to the tropical hot climate, A. annua
      could not be planted for production of artemisinin, the main bioactive compound.
      In this study, the leaves of three in vitro A. annua L. clones were, extracted
      and two bioactive compounds, artemisinin and a precursor, were isolated by thin
      layer chromatography. These compounds were found to be effective in inhibiting
      the growth of Gram-positive and Gram-negative bacteria but not Candida albicans.
      Their antimicrobial activity was similar to that of antibactericidal antibiotic
      streptomycin. They were found to inhibit the growth of the tested microbes at the
      minimum inhibition concentration of 0.09 mg/mL, and toxicity test using brine
      shrimp showed that even the low concentration of 0.09 mg/mL was very lethal
      towards the brine shrimps with 100% mortality rate. This study hence indicated
      that in vitro cultured plantlets of A. annua can be used as the alternative
      method for production of artemisinin and its precursor with antimicrobial
      activities. 

PMID- 24575402
TI  - Construction of a novel liver-targeting fusion interferon by incorporation of a
      Plasmodium region I-plus peptide.
AB  - Interferon alpha (IFN alpha) exerts a multiplicity of biological actions
      including antiviral, immunomodulatory, and antiproliferative effects.
      Administration of IFN alpha is the current treatment for chronic hepatitis B;
      however, therapy outcome has not been completely satisfactory. The systemic
      effects of IFN alpha may account for its low in vivo biological activity and
      multiple adverse events. The purpose of this study was to design a novel liver
      targeting fusion interferon (IFN-CSP) by fusing IFN alpha2b with a Plasmodium
      region I-plus peptide, thus targeting the drug specifically to the liver. The DNA
      sequence encoding IFN-CSP was constructed using improved splicing by overlapping
      extension-PCR method, and then cloned into the pET-21b vector for protein
      expression in E. coli BL21 (DE3). The recombinant protein was expressed as a His
      tagged protein and purified using a combination of Ni affinity and HiTrap
      affinity chromatography at a purity of over 95%. The final yield of biologically
      active IFN-CSP was up to 270 mg/L culture. The purified recombinant protein
      showed anti-HBV activity and liver-targeting potentiality in vitro. These data
      suggests that the novel fusion interferon IFN-CSP may be an excellent candidate
      as a liver-targeting anti-HBV agent.

PMID- 24575403
TI  - Changes in bacterial population of gastrointestinal tract of weaned pigs fed with
      different additives.
AB  - This study aimed to provide novel insights into the gastrointestinal microbial
      diversity from different gastrointestinal locations in weaning piglets using PCR
      restriction fragment length polymorphism (PCR-RFLP). Additionally, the effect of
      different feed additives was analyzed. Thirty-two piglets were fed with four
      different diets: a control group and three enriched diets, with avilamycin,
      sodium butyrate, and a plant extract mixture. Digesta samples were collected from
      eight different gastrointestinal segments of each animal and the bacterial
      population was analysed by a PCR-RFLP technique that uses 16S rDNA gene
      sequences. Bacterial diversity was assessed by calculating the number of bands
      and the Shannon-Weaver index. Dendrograms were constructed to estimate the
      similarity of bacterial populations. A higher bacterial diversity was detected in
      large intestine compared to small intestine. Among diets, the most relevant
      microbial diversity differences were found between sodium butyrate and plant
      extract mixture. Proximal jejunum, ileum, and proximal colon were identified as
      those segments that could be representative of microbial diversity in pig gut.
      Results indicate that PCR-RFLP technique allowed detecting modifications on the
      gastrointestinal microbial ecology in pigs fed with different additives, such as
      increased biodiversity by sodium butyrate in feed. 

PMID- 24575400
TI  - Adipose tissue-derived stem cell secreted IGF-1 protects myoblasts from the
      negative effect of myostatin.
AB  - Myostatin, a TGF-beta family member, is associated with inhibition of muscle
      growth and differentiation and might interact with the IGF-1 signaling pathway.
      Since IGF-1 is secreted at a bioactive level by adipose tissue-derived
      mesenchymal stem cells (ASCs), these cells (ASCs) provide a therapeutic option
      for Duchenne Muscular Dystrophy (DMD). But the protective effect of stem cell
      secreted IGF-1 on myoblast under high level of myostatin remains unclear. In the
      present study murine myoblasts were exposed to myostatin under presence of ASCs
      conditioned medium and investigated for proliferation and apoptosis. The
      protective effect of IGF-1 was further examined by using IGF-1 neutralizing and
      receptor antibodies as well as gene silencing RNAi technology. MyoD expression
      was detected to identify impact of IGF-1 on myoblasts differentiation when
      exposed to myostatin. IGF-1 was accountable for 43.6% of the antiapoptotic impact
      and 48.8% for the proliferative effect of ASCs conditioned medium. Furthermore,
      IGF-1 restored mRNA and protein MyoD expression of myoblasts under risk. Beside
      fusion and transdifferentiation the beneficial effect of ASCs is mediated by
      paracrine secreted cytokines, particularly IGF-1. The present study underlines
      the potential of ASCs as a therapeutic option for Duchenne muscular dystrophy and
      other dystrophic muscle diseases.

PMID- 24575399
TI  - The impact of cholesterol, DHA, and sphingolipids on Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a devastating neurodegenerative disorder currently
      affecting over 35 million people worldwide. Pathological hallmarks of AD are
      massive amyloidosis, extracellular senile plaques, and intracellular
      neurofibrillary tangles accompanied by an excessive loss of synapses. Major
      constituents of senile plaques are 40-42 amino acid long peptides termed beta 
      amyloid (A beta ). A beta is produced by sequential proteolytic processing of the
      amyloid precursor protein (APP). APP processing and A beta production have been
      one of the central scopes in AD research in the past. In the last years, lipids
      and lipid-related issues are more frequently discussed to contribute to the AD
      pathogenesis. This review summarizes lipid alterations found in AD postmortem
      brains, AD transgenic mouse models, and the current understanding of how lipids
      influence the molecular mechanisms leading to AD and A beta generation, focusing
      especially on cholesterol, docosahexaenoic acid (DHA), and
      sphingolipids/glycosphingolipids. 

PMID- 24575404
TI  - Microsatellites in the genome of the edible mushroom, Volvariella volvacea.
AB  - Using bioinformatics software and database, we have characterized the
      microsatellite pattern in the V. volvacea genome and compared it with
      microsatellite patterns found in the genomes of four other edible fungi:
      Coprinopsis cinerea, Schizophyllum commune, Agaricus bisporus, and Pleurotus
      ostreatus. A total of 1346 microsatellites have been identified, with mono
      nucleotides being the most frequent motif. The relative abundance of
      microsatellites was lower in coding regions with 21 No./Mb. However, the
      microsatellites in the V. volvacea gene models showed a greater tendency to be
      located in the CDS regions. There was also a higher preponderance of
      trinucleotide repeats, especially in the kinase genes, which implied a possible
      role in phenotypic variation. Among the five fungal genomes, microsatellite
      abundance appeared to be unrelated to genome size. Furthermore, the short motifs
      (mono- to tri-nucleotides) outnumbered other categories although these differed
      in proportion. Data analysis indicated a possible relationship between the most
      frequent microsatellite types and the genetic distance between the five fungal
      genomes. 

PMID- 24575405
TI  - CD49b, a major marker of regulatory T-cells type 1, predicts the response to
      antiviral therapy of recurrent hepatitis C after liver transplantation.
AB  - The TRANSPEG study was a prospective study to assess the efficacy of antiviral
      therapy in patients with a recurrent hepatitis C virus (HCV) after liver
      transplantation. The influence of regulatory T-cells (Tregs) on the response to
      antiviral therapy was analyzed. Patients were considered as a function of their
      sustained virological response (SVR) at 18 months after treatment initiation. A
      transcriptomic analysis was performed to assess Treg markers (Tr1 and FoxP3(+))
      in serum, PBMC, and liver biopsies. 100 patients had been included in the
      TRANSPEG study. Data from 27 of these patients were available. The results showed
      that the expression of CD49b (a predominant marker of Tr1) before the
      introduction of antiviral therapy was significantly associated with SVR.
      Responders displayed lower serum levels of CD49b than nonresponders (P < 0.02).
      These findings were confirmed in PBMC and liver biopsies even if in a
      nonsignificant manner for the limited number of samples. The assessment of CD49b
      levels is thus predictive of the response to antiviral therapy. This data
      suggests that CD49b may be a marker of the failure of the immune response and
      antiviral therapy during HCV recurrence. The assessment of CD49b could help to
      select patients who require earlier and more intensive antiviral therapy. 

PMID- 24575406
TI  - Synergistic effects of orbital shear stress on in vitro growth and osteogenic
      differentiation of human alveolar bone-derived mesenchymal stem cells.
AB  - Cellular behavior is dependent on a variety of physical cues required for normal
      tissue function. In order to mimic native tissue environments, human alveolar
      bone-derived mesenchymal stem cells (hABMSCs) were exposed to orbital shear
      stress (OSS) in a low-speed orbital shaker. The synergistic effects of OSS on
      proliferation and differentiation of hABMSCs were investigated. In particular, we
      induced the osteoblastic differentiation of hABMSCs cultured in the absence of OM
      by exposing hABMSCs to OSS (0.86-1.51 dyne/cm(2)). Activation of Cx43 was
      associated with exposure of hABMSCs to OSS. The viability of cells stimulated for
      10, 30, 60, 120, and 180 min/day increased by approximately 10% compared with
      that of control. The OSS groups with stimulation of 10, 30, and 60 min/day had
      more intense mineralized nodules compared with the control group. In
      quantification of vascular endothelial growth factor (VEGF) and bone
      morphogenetic protein-2 (BMP-2) protein, VEGF protein levels under stimulation
      for 10, 60, and 180 min/day and BMP-2 levels under stimulation for 60, 120, and
      180 min/day were significantly different compared with those of the control. In
      conclusion, the results indicated that exposing hABMSCs to OSS enhanced their
      differentiation and maturation. 

PMID- 24575407
TI  - Matrix effects on the stability and antioxidant activity of red cabbage
      anthocyanins under simulated gastrointestinal digestion.
AB  - Red cabbage is, among different vegetables, one of the major sources of
      anthocyanins. In the present study an in vitro digestion method has been used to
      assay the influence of the physiological conditions in the stomach and small
      intestine, as well as faecal microflora on anthocyanins stability in red cabbage
      and anthocyanin-rich extract. The recovery of anthocyanins during in vitro
      gastrointestinal digestion was strongly influenced by food matrix. The results
      showed that other constituents present in cabbage enhanced the stability of
      anthocyanins during the digestion. The amount of anthocyanins (HPLC method) and
      antioxidant capacity (ABTS and FRAP assays) strongly decreased after pancreatic
      bile digestion in both matrices but total phenolics content (Folin-Ciocalteu
      assay) in these digestions was higher than in initial samples. Incubation with
      human faecal microflora caused further decline in anthocyanins content. The
      results obtained suggest that intact anthocyanins in gastric and products of
      their decomposition in small and large intestine may be mainly responsible for
      the antioxidant activity and other physiological effects after consumption of red
      cabbage. 

PMID- 24575408
TI  - Changing the landscape of the HIV epidemic among MSM in China: results from three
      consecutive respondent-driven sampling surveys from 2009 to 2011.
AB  - This study assessed the changes of HIV incidence and its predictors among
      Beijing's men who have sex with men (MSM). Three consecutive cross-sectional
      surveys were carried out using a consistent respondent-driven sampling (RDS)
      approach in 2009, 2010, and 2011, respectively. Structured-questionnaire based
      interviews were completed with computer-assisted self-administration. Incident
      infection was examined with BED capture enzyme immunoassay (BED-CEIA). The
      overall rate of HIV prevalence was 8.0% in the three years (95% confidence
      interval [CI]: 4.9%-11.2%). The overall rate of BED-CEIA incidence was 7.8/100
      person years (PY) (95% CI: 5.5-10.1) with 6.8/100PY (95% CI: 3.4-10.2) in 2009,
      11.2/100PY (95% CI: 6.2-16.3) in 2010, and 5.8/100PY (95% CI: 2.4-9.3) in 2011,
      respectively. Multivariable logistic regression analysis revealed that, compared
      with HIV-negative MSM, recently infected MSM were more likely to be bisexual
      (adjusted odds ratio [AOR] = 2.1, 95% CI: 1.1-4.1), live in Beijing <=3 years
      (AOR = 2.1, 95% CI: 1.2-4.0), and have a negative attitude towards safe sex (AOR
      = 1.1 per scale point, 95% CI: 1.0-1.1). This study demonstrated a disturbing
      rise of HIV infections among Beijing's MSM. These findings underscored the
      urgency of scaling up effective and better-targeted intervention services to stop
      the rapid spread of the virus. 

PMID- 24575409
TI  - Characterization of uptake and internalization of exosomes by bladder cancer
      cells.
AB  - Bladder tumors represent a special therapeutic challenge as they have a high
      recurrence rate requiring repeated interventions and may progress to invasive or
      metastatic disease. Exosomes carry proteins implicated in bladder cancer
      progression and have been implicated in bladder cancer cell survival. Here, we
      characterized exosome uptake and internalization by human bladder cancer cells
      using Amnis ImageStreamX, an image cytometer. Exosomes were isolated by
      ultracentrifugation from bladder cancer culture conditioned supernatant, labeled
      with PKH-26, and analyzed on the ImageStreamX with an internal standard added to
      determine concentration. Exosomes were cocultured with bladder cancer cells and
      analyzed for internalization. Using the IDEAS software, we determined exosome
      uptake based on the number of PKH-26+ spots and overall PKH-26 fluorescence
      intensity. Using unlabeled beads of a known concentration and size, we were able
      to determine concentrations of exosomes isolated from bladder cancer cells. We
      measured exosome uptake by recipient bladder cancer cells, and we demonstrated
      that uptake is dose and time dependent. Finally, we found that uptake is active
      and specific, which can be partially blocked by heparin treatment. The
      characterization of cellular uptake and internalization by bladder cancer cells
      may shed light on the role of exosomes on bladder cancer recurrence and
      progression. 

PMID- 24575411
TI  - Neuroanatomical classification in a population-based sample of psychotic major
      depression and bipolar I disorder with 1 year of diagnostic stability.
AB  - The presence of psychotic features in the course of a depressive disorder is
      known to increase the risk for bipolarity, but the early identification of such
      cases remains challenging in clinical practice. In the present study, we
      evaluated the diagnostic performance of a neuroanatomical pattern classification
      method in the discrimination between psychotic major depressive disorder (MDD),
      bipolar I disorder (BD-I), and healthy controls (HC) using a homogenous sample of
      patients at an early course of their illness. Twenty-three cases of first-episode
      psychotic mania (BD-I) and 19 individuals with a first episode of psychotic MDD
      whose diagnosis remained stable during 1 year of followup underwent 1.5 T MRI at
      baseline. A previously validated multivariate classifier based on support vector
      machine (SVM) was employed and measures of diagnostic performance were obtained
      for the discrimination between each diagnostic group and subsamples of age- and
      gender-matched controls recruited in the same neighborhood of the patients. Based
      on T1-weighted images only, the SVM-classifier afforded poor discrimination in
      all 3 pairwise comparisons: BD-I versus HC; MDD versus HC; and BD-I versus MDD.
      Thus, at the population level and using structural MRI only, we failed to achieve
      good discrimination between BD-I, psychotic MDD, and HC in this proof of concept
      study. 

PMID- 24575410
TI  - Extended endoscopic endonasal approaches for cerebral aneurysms: anatomical,
      virtual reality and morphometric study.
AB  - INTRODUCTION: The purpose of the present contribution is to perform a detailed
      anatomic and virtual reality three-dimensional stereoscopic study in order to
      test the effectiveness of the extended endoscopic endonasal approaches for
      selected anterior and posterior circulation aneurysms. METHODS: The study was
      divided in two main steps: (1) simulation step, using a dedicated Virtual Reality
      System (Dextroscope, Volume Interactions); (2) dissection step, in which the
      feasibility to reach specific vascular territory via the nose was verified in the
      anatomical laboratory. RESULTS: Good visualization and proximal and distal
      vascular control of the main midline anterior and posterior circulation territory
      were achieved during the simulation step as well as in the dissection step
      (anterior communicating complex, internal carotid, ophthalmic, superior
      hypophyseal, posterior cerebral and posterior communicating, basilar, superior
      cerebellar, anterior inferior cerebellar, vertebral, and posterior inferior
      cerebellar arteries). CONCLUSION: The present contribution is intended as
      strictly anatomic study in which we highlighted some specific anterior and
      posterior circulation aneurysms that can be reached via the nose. For clinical
      applications of these approaches, some relevant complications, mainly related to
      the endonasal route, such as proximal and distal vascular control, major arterial
      bleeding, postoperative cerebrospinal fluid leak, and olfactory disturbances must
      be considered.

PMID- 24575413
TI  - Antiproliferative activity of the isofuranonaphthoquinone isolated from Bulbine
      frutescens against Jurkat T cells.
AB  - Cancer is a major public health burden in both developed and developing
      countries. The quinone moiety has been shown to possess antitumor activity and
      several cancer drugs in clinical use contain this entity. The effect of
      isofuranonaphthoquinone isolated from Bulbine frutescens on Jurkat T cells was
      determined. Cells were exposed to the isofuranonaphthoquinone (IFNQ) at different
      concentrations. Significant antiproliferative effects were observed which were
      comparable to that of the anticancer drug 1,3-bis(2-chloroethyl)-1-nitrosourea
      (BCNU). A combination of IFNQ with BCNU produced synergistic effects which were
      observed after 72 hrs. It was also observed that combining IFNQ with reduced
      glutathione abolished the anticancer activity of the compound. It is, therefore,
      proposed that the isofuranonaphthoquinone may exert part of its effect by
      producing reactive oxygen species resulting in death of the cells as the effects
      of this compound were antagonized by reduced glutathione. An investigation on the
      effects of isofuranonaphthoquinone on glutathione transferase (GST) activity and
      drug efflux pumps showed that this compound exhibited inhibitory effects on both
      the GST and the drug efflux pumping activities. Thus, the isofuranonaphthoquinone
      showed cytotoxicity, works through inhibition of some cellular mechanisms, and
      could present a potential source of lead compounds for anticancer drug
      development. 

PMID- 24575414
TI  - Soluplus graft copolymer: potential novel carrier polymer in electrospinning of
      nanofibrous drug delivery systems for wound therapy.
AB  - Electrospinning is an effective method in preparing polymeric nanofibrous drug
      delivery systems (DDSs) for topical wound healing and skin burn therapy
      applications. The aim of the present study was to investigate a new synthetic
      graft copolymer (Soluplus) as a hydrophilic carrier polymer in electrospinning of
      nanofibrous DDSs. Soluplus (polyvinyl caprolactam-polyvinyl acetate-polyethylene
      glycol graft copolymer (PCL-PVAc-PEG)) was applied in the nonwoven nanomats
      loaded with piroxicam (PRX) as a poorly water-soluble drug. Raman spectroscopy, X
      ray powder diffraction, differential scanning calorimetry, and scanning electron
      microscopy (SEM) were used in the physical characterization of nanofibrous DDSs.
      According to the SEM results, the drug-loaded PCL-PVAc-PEG nanofibers were
      circular in cross-section with an average diameter ranging from 500 nm up to 2 
      um. Electrospinning stabilized the amorphous state of PRX. In addition,
      consistent and sustained-release profile was achieved with the present
      nanofibrous DDSs at the physiologically relevant temperature and pH applicable in
      wound healing therapy. In conclusion, electrospinning can be used to prepare
      nanofibrous DDSs of PCL-PVAc-PEG graft copolymer (Soluplus) and to stabilize the
      amorphous state of a poorly water-soluble PRX. The use of this synthetic graft
      copolymer can open new options to formulate nanofibrous DDSs for wound healing.

PMID- 24575415
TI  - Role of ethyl pyruvate in systemic inflammatory response and lung injury in an
      experimental model of ruptured abdominal aortic aneurysm.
AB  - OBJECTIVE: The purpose of this study is to evaluate the effect of ethyl pyruvate
      (EP) on systemic inflammatory response and lung injury in an experimental rat
      model of ruptured abdominal aortic anurysm (RAAA). METHODS: Anaesthetized 30
      Sprague-Dawley male rats were randomized to sham (Sh n : 6) (Sh + EP n : 6) or
      shock and clamp (S/C) groups (S/C n : 9) (S/C + EP n : 9). In the S/C and S/C +
      EP groups, hemorrhagic shock, lower torso ischemia, and reperfusion were created,
      S/C group was given 1 mL saline and S/C + EP group was given 40 mg/kg EP. At the
      end of reperfusion process some biochemical and histological parameters were
      studied in serum and lung tissues. RESULTS: An increase was observed in all
      parameters except interleukin-6 (IL-6) in the S/C group in comparison to the sham
      groups. In the S/C + EP group, serum myeloperoxydase (MPO), malondialdehyde
      (MDA), and tumor necrosis factor alpha (TNF-alpha) as well as lung MPO and MDA
      values decreased significantly (P < 0.016). In the lung tissues, histological
      injury scores and lung tissue wet/dry ratio were significantly decreased in the
      S/C + EP group as compared to the S/C group (P < 0.016). CONCLUSIONS: Ethyl
      pyruvate may reduce systemic inflammatory response and lung injury which resulted
      from shock and ischemia/reperfusion in an experimental model of RAAA.

PMID- 24575416
TI  - A standardized method for 4D ultrasound-guided peripheral nerve blockade and
      catheter placement.
AB  - We present a standardized method for using four-dimensional ultrasound (4D US)
      guidance for peripheral nerve blocks. 4D US allows for needle tracking in
      multiple planes simultaneously and accurate measurement of the local anesthetic
      volume surrounding the nerve following injection. Additionally, the morphology
      and proximity of local anesthetic spread around the target nerve is clearly seen
      with the described technique. This method provides additional spatial information
      in real time compared to standard two-dimensional ultrasound. 

PMID- 24575417
TI  - Adverse prognostic factors and optimal intervention time for
      kyphoplasty/vertebroplasty in osteoporotic fractures.
AB  - INTRODUCTION: While evidence supports the efficacy of vertebral augmentation
      (kyphoplasty and vertebroplasty) for the treatment of osteoporotic fractures,
      randomized trials disputed the value of vertebroplasty. The aim of this analysis
      is to determine the subset of patients that may not benefit from surgical
      intervention and find the optimal intervention time. METHODS: 27 prospective
      multiple-arm studies with cohorts of more than 20 patients were included in this
      meta-analysis. We hereby report the results from the metaregression and subset
      analysis of those trials reporting on treatment of osteoporotic fractures with
      kyphoplasty and/or vertebroplasty. RESULTS: Early intervention (first 7 weeks
      after fracture) yielded more pain relief. However, spontaneous recovery was
      encountered in hyperacute fractures (less than 2 weeks old). Patients suffering
      from thoracic fractures or severely deformed vertebrae tended to report inferior
      results. We also attempted to formulate a treatment algorithm. CONCLUSION:
      Intervention in the hyperacute period should not be pursued, while augmentation
      after 7 weeks yields less consistent results. In cases of thoracic fractures and
      significant vertebral collapse, surgeons or interventional radiologists may
      resort earlier to operation and be less conservative, although those parameters
      need to be addressed in future randomized trials.

PMID- 24575420
TI  - Ultrasound-assisted magnetic solid-phase extraction based ionic liquid-coated
      Fe3O4@graphene for the determination of nitrobenzene compounds in environmental
      water samples.
AB  - An ultrasound-assisted magnetic solid-phase extraction procedure with the
      [C7MIM][PF6] ionic liquid-coated Fe3O4-grafted graphene nanocomposite as the
      magnetic adsorbent has been developed for the determination of five nitrobenzene
      compounds (NBs) in environmental water samples, in combination with high
      performance liquid chromatography-photodiode array detector (HPLC-PDA). Several
      significant factors that affect the extraction efficiency, such as the types of
      magnetic nanoparticle and ionic liquid, the volume of ionic liquid and the amount
      of magnetic nanoparticles, extraction time, ionic strength, and solution pH, were
      investigated. With the assistance of ultrasound, adsorbing nitrobenzene compounds
      by ionic liquid and self-aggregating ionic liquid onto the surface of the Fe3O4
      grafted graphene proceeded synchronously, which made the extraction achieved the
      maximum within 20 min using only 144 MUL [C7MIM][PF6] and 3 mg Fe3O4-grafted
      graphene. Under the optimized conditions, satisfactory linearities were obtained
      for all NBs with correlation coefficients larger than 0.9990. The mean recoveries
      at two spiked levels ranged from 80.35 to 102.77%. Attributed to the convenient
      magnetic separation, the Fe3O4-grafted graphene could be recycled many times. The
      proposed method was demonstrated to be feasible, simple, solvent-saving and easy
      to operate for the trace analysis of NBs in environmental water samples. 

PMID- 24575421
TI  - A two-photon "turn-on" fluorescent probe based on carbon nanodots for imaging and
      selective biosensing of hydrogen sulfide in live cells and tissues.
AB  - Determination of hydrogen sulfide (H2S) in live cells and tissues is still a
      challenge for evaluating the key roles that H2S plays in physiological and
      pathological processes. In this work, a "turn-on" two-photon fluorescent (TPF)
      sensor for H2S is developed, in which carbon nanodot (C-Dot) was employed as a
      two-photon fluorophore due to its large two-photon absorption cross-section
      (sigma), and AE-TPEA-Cu(2+) complex [AE-TPEA = N-(2-aminoethyl)-N,N,N'
      tris(pyridin-2-ylmethyl)ethane-1,2-diamine] was first designed as a specific
      receptor for H2S. The fluorescence of C-Dot conjugated with AE-TPEA (C-Dot-TPEA)
      was quenched upon the addition of Cu(2+). Then, the fluorescence was restored
      after the addition of H2S, because Cu(2+) could be released from TPEA binding
      site when H2S interacted with the Cu(2+) ion. The designed C-Dot-TPEA-Cu(2+)
      fluorescent sensor exhibited high specificity for H2S over biothiols, sulfur
      containing compounds, reactive oxygen species (ROS), and other biological
      interferences. Meanwhile, a broad linear range from 5 MUM to 100 MUM was obtained
      and the detection limit was achieved to 0.7 MUM. In addition, the C-Dot-based TPF
      probe exhibited bright two-photon fluorescence, favourable photostability against
      light illumination and pH change, and low cytotoxicity. Accordingly, the
      nanohybridized TPF sensor with high selectivity and sensitivity, as well as the
      fascinating properties of C-Dot themselves, successfully provided a new way for
      TPF imaging and biosensing of H2S in live cells and tissues. We believe this is
      the first report of TPF imaging and biosensing of H2S in live cells and tissues
      using a specially engineered C-Dot-based nanosystem. 

PMID- 24575418
TI  - MicroRNA in diabetic nephropathy: renin angiotensin, aGE/RAGE, and oxidative
      stress pathway.
AB  - MicroRNAs (miRNA) are a novel class of small, noncoding RNA molecules that have
      gained the attention of many researchers in recent years due to their ability to
      posttranscriptionally regulate the expression of families of genes
      simultaneously. Their role in normal physiology and pathobiology is intriguing
      and their regulation in normal and disease states is fascinating. That the cells
      can return to a state of homeostasis when these small molecules are perturbed is
      truly remarkable given the multiple cellular targets of each miRNA and that many
      mRNAs are targeted by multiple miRNAs. Several reviews have covered aspects of
      miRNA function in biology and disease. Here, we review the role of miRNA in
      regulating the renin-angiotensin system, AGE/RAGE signalling, and under
      conditions of oxidative stress in the context of diabetic nephropathy. 

PMID- 24575419
TI  - Gender expression, sexual orientation and pain sensitivity in women.
AB  - BACKGROUND: Despite a growing body of literature investigating sex differences
      with regard to pain, surprisingly little research has been conducted on the
      influence of various aspects of self-identity, including gender expression and
      sexual orientation, on pain sensitivity within each sex, particularly among
      women. In men, dispositional femininity is linked to greater clinical pain and
      trait masculinity is associated with higher pain thresholds. OBJECTIVES: To
      examine whether gender expression and sexual orientation are associated with
      within-sex differences in ischemic pain sensitivity in healthy young women.
      METHODS: A convenience sample of 172 females (mean age 21.4 years; range 18 to 30
      years of age; 56.0% white, 89% heterosexual) performed an ischemic pain task in
      counterbalanced order. Desired levels of dispositional femininity for a preferred
      romantic partner and self-described levels of personal dispositional femininity
      were measured. RESULTS: Compared with heterosexual women, lesbian and bisexual
      women reported lower pain intensity ratings early in the discomfort task.
      Irrespective of sexual orientation, attraction to more feminine romantic partners
      and dispositional masculinity were correlated with lower pain intensity, and with
      higher pain thresholds and tolerance levels. DISCUSSION: These preliminary
      findings suggest that within-sex differences in sexual orientation and other
      aspects of identity, irrespective of biological sex, may be important to consider
      when examining experimental pain performance and clinical pain experiences.
      CONCLUSION: Larger investigations of the psychophysiological relationships among
      sexual orientation, gender expression and pain sensitivity are warranted. These
      findings may have implications for differences in clinical pain sensitivity of
      lesbian and bisexual women compared with heterosexual women.

PMID- 24575422
TI  - Innovative fabrication of a Au nanoparticle-decorated SiO2 mask and its activity
      on surface-enhanced Raman scattering.
AB  - Surface-enhanced Raman scattering (SERS) utilizing the well-defined localized
      surface plasmon resonance (LSPR) of Ag and Au nanoparticles (NPs) under resonant
      irradiation has emerged as a promising spectroscopy technique for providing
      vibrational information on trace molecules. The Raman scattering intensity from
      molecules close to the surface of these finely divided metals can be
      significantly enhanced by a factor of more than 10(6). In addition to the high
      sensitivity, the reproducibility of the SERS signal is also an important
      parameter for its reliable application. In this work, we report on the innovative
      and facile fabrication of a Au NP-decorated SiO2 mask coated on indium tin oxide
      (ITO) glass as a SERS array substrate. First, a highly ordered porous SiO2 mask
      with pore sizes of 350 nm in diameter and wall thickness of 60 nm was deposited
      on ITO glass by using spin coating. Then, Au NPs were controllably decorated into
      the pores of the conductive ITO glass-bottomed SiO2 mask by using
      sonoelectrochemical deposition-dissolution cycling (SEDDC). Experimental results
      indicate that the SERS effect of Rhodamine 6G (R6G) observed on this developed
      substrate increases with an increase in the deposition time of Au NPs in SEDDC.
      The corresponding optimal enhancement factor (EF) that is obtained is ca. 6.5 *
      10(7). Significantly, this system achieves an optimal reproducibility under a
      medium-length deposition time of Au NPs in SEDDC with a relative standard
      deviation (RSD) of 12% for measurements of five spots on different areas. The low
      RSD of the SERS signal and the large EF suggest that the developed array system
      can serve as an excellent spectroscopy platform for practical applications in
      analytical chemistry. 

PMID- 24575423
TI  - Turn-on fluorescence triggered by selective internal dye replacement in MOFs.
AB  - Coordinatively unsaturated metal sites (CUS) are used to create dye
      functionalized metal-organic frameworks (MOFs). The quenching of dye fluorescence
      through interactions with the CUS can be utilised for chemical sensing of Lewis
      bases that displace the dye from the CUS, resulting in a triggered turn-on
      fluorescence signal. 

PMID- 24575424
TI  - Adhesion behaviors on superhydrophobic surfaces.
AB  - The adhesion behaviors of superhydrophobic surfaces have become an emerging topic
      to researchers in various fields as a vital step in the interactions between
      materials and organisms/materials. Controlling the chemical compositions and
      topological structures via various methods or technologies is essential to
      fabricate and modulate different adhesion properties, such as low-adhesion, high
      adhesion and anisotropic adhesion on superhydrophobic surfaces. We summarize the
      recent developments in both natural superhydrophobic surfaces and artificial
      superhydrophobic surfaces with various adhesions and also pay attention to
      superhydrophobic surfaces switching between low- and high-adhesion. The methods
      to regulate or translate the adhesion of superhydrophobic surfaces can be
      considered from two perspectives. One is to control the chemical composition and
      change the surface geometric structure on the surfaces, respectively or
      simultaneously. The other is to provide external stimulations to induce
      transitions, which is the most common method for obtaining switchable adhesions.
      Additionally, adhesion behaviors on solid-solid interfaces, such as the behaviors
      of cells, bacteria, biomolecules and icing on superhydrophobic surfaces are also
      noticeable and controversial. This review is aimed at giving a brief and crucial
      overview of adhesion behaviors on superhydrophobic surfaces. 

PMID- 24575425
TI  - Phototriggered formation and disappearance of surface-confined self-assembly
      composed of photochromic 2-thienyl-type diarylethene: a cooperative model at the
      liquid/solid interface.
AB  - A photoresponsive self-assembly on a 2-D surface was investigated by scanning
      tunnelling microscopy (STM). The open-ring isomer of a diarylethene derivative
      showed an abrupt ordering formation at a critical concentration, which was
      successfully reproduced by a cooperative model based on Langmuir-type adsorption.

PMID- 24575426
TI  - Dopamine-induced silica-polydopamine hybrids with controllable morphology.
AB  - Novel silica-polydopamine hybrids, with controllable morphology, are facilely
      fabricated in an emulsion system consisting of tetraethyl orthosilicate,
      dopamine, water, and NaOH under weakly basic conditions (pH 8.5-10). An increase
      in initial pH favors the formation of nano-structured spherical silica-PDA
      hybrids from a flocculated structure. 

PMID- 24575427
TI  - Palladium(0)-catalyzed cyclopropanation of benzyl bromides via C(sp3)-H bond
      activation.
AB  - A novel and highly efficient Pd(0)-catalyzed domino reaction to prepare
      cyclopropane derivatives has been established. The process involves a Heck-type
      coupling reaction and a C(sp(3))-H bond activation. Preliminary DFT calculations
      suggest that a four-membered palladacycle intermediate is involved. 

PMID- 24575428
TI  - Positively charged graphene oxide nanoparticle: precisely label the plasma
      membrane of live cell and sensitively monitor extracellular pH in situ.
AB  - Polyethylene glycol modified graphene oxide (GO-PEG) nanoparticles were prepared,
      which were positively charged and fairly stable in buffer solution. The GO-PEG
      nanoparticles possess a special affinity to the plasma membrane of live cells,
      and their yellowish-green fluorescence is sensitively responsive to the
      extracellular physiological solution in situ. 

PMID- 24575429
TI  - Unprecedented non-aromatic, conformationally locked dibenzohexaphyrin analogs
      carrying multiple meso-exocyclic double bonds.
AB  - Acid-catalysed, '3+3' condensation of m-bispyrryl benzene derivatives with
      acetone afforded new non-aromatic macrocycles that can be converted to meso
      alkylidenyl dibenzohexaphyrins carrying four exocyclic double bonds at meso
      positions by DDQ oxidation. 

PMID- 24575430
TI  - Synthesis of antimicrobial cyclodextrins bearing polyarylamino and polyalkylamino
      groups via click chemistry for bacterial membrane disruption.
AB  - Cyclodextrin derivatives are synthesized as membrane-disrupting agents via a
      microwave-assisted Huisgen reaction. Their ability to permeabilize bacterial
      membranes depends on the amino substituents and an appropriate balance of
      hydrophobicity and hydrophilicity, thus enabling the preparation of derivatives
      with selective toxicity against bacteria. 

PMID- 24575431
TI  - Photo-responsive self-assembly based on a water-soluble pillar[6]arene and an
      azobenzene-containing amphiphile in water.
AB  - Photo-responsive self-assembly in water based on the molecular recognition motif
      between a water-soluble pillar[6]arene host and an azobenzene-containing
      amphiphilic guest in water was investigated. 

PMID- 24575432
TI  - Commentary on 'Prevalence and predictors of anal incontinence during pregnancy
      and 1 year after delivery: a prospective cohort study'.

PMID- 24575433
TI  - Commentary on 'Effect of ethnicity on live birth rates after in vitro
      fertilisation or intracytoplasmic sperm injection treatment'.

PMID- 24575434
TI  - Commentary on 'Community-based distribution of misoprostol: is this the way
      forward?'.

PMID- 24575436
TI  - European report card issued.

PMID- 24575435
TI  - Commentary on 'Risk of colorectal cancer in women with pelvic inflammatory
      disease: a matched cohort study'.

PMID- 24575437
TI  - [Bacteriophages: an alternative to antibiotics?].

PMID- 24575439
TI  - Why the Cochrane risk of bias tool should include funding source as a standard
      item.

PMID- 24575438
TI  - EVOLUTION--taking charge and growing stronger: the design, acceptability, and
      feasibility of a secondary prevention empowerment intervention for young women
      living with HIV.
AB  - In the United States, youth of 13-24 years account for nearly a quarter of all
      new HIV infections, with almost 1000 young men and women being infected per
      month. Young women account for 20% of those new infections.This article describes
      the design, feasibility, and acceptability of a secondary prevention empowerment
      intervention for young women living with HIV entitled EVOLUTION: Young Women
      Taking Charge and Growing Stronger. The nine session intervention aimed to reduce
      secondary transmission by enhancing social and behavioral skills and knowledge
      pertaining to young women's physical, social, emotional, and sexual well
      being,while addressing the moderating factors such as sexual inequality and power
      imbalances. Process evaluation data suggest that EVOLUTION is a highly acceptable
      and feasible intervention for young women living with HIV. Participants reported
      enjoying both the structure and comprehensive nature of the intervention. Both
      participants and interventionists reported that the intervention was highly
      relevant to the lives of young women living with HIV since it not only provided
      opportunities for them to broaden their knowledge and risk reduction skills in
      HIV, but it also addressed important areas that impact their daily lives such as
      stressors, relationships,and their emotional and social well-being. Thus, this
      study demonstrates that providing a gender-specific,comprehensive group-based
      empowerment intervention for young women living with HIV appears to be both
      feasible and acceptable.

PMID- 24575440
TI  - Why the Cochrane risk of bias tool should not include funding source as a
      standard item.

PMID- 24575441
TI  - A 747 in the age of A380s: how can Cochrane learn from the past and compete 20
      years on?

PMID- 24575442
TI  - Management guidelines for gastrointestinal neuroendocrine neoplasm.

PMID- 24575443
TI  - A new dietary paradiagm?

PMID- 24575444
TI  - LCHF: look at the full picture.

PMID- 24575445
TI  - Refractory anemia with ring sideroblasts associated with thrombocytosis (RARS-T).

PMID- 24575446
TI  - Acute myeloid leukemia relapse first presenting in the cerebrospinal fluid.

PMID- 24575456
TI  - Mental healthcare in the community.

PMID- 24575458
TI  - An update on attention deficit hyperactivity disorder (ADHD).

PMID- 24575457
TI  - A broad diagnostic framework to simplify the approach to mental disorders in
      primary care.
AB  - Overemphasis on detailed classification of a psychiatic disorder at a primary
      level assessment may be unhelpful and prone to error. True rigour demands a
      continuous process of hypothesis formation that guides further enquiry. A simple
      categorisation of priority conditions provides a useful framework for a process.
      This approach has been set out by the World Health Organization (WHO) Mental
      Health Gap Action Program (MHGAP) Intervention Guide, which can then be adapted
      for use in the South African context. This then provides the basis for further
      enquiry and risk assessment at the initial consultation.

PMID- 24575459
TI  - Outpatient management of adult alcoholism.

PMID- 24575460
TI  - Psychiatry in primary care using the three-stage assessment.

PMID- 24575461
TI  - Adapting the psychiatric assessment for primary care.

PMID- 24575462
TI  - De-institutionalisation in psychiatry-both sides of the coin.

PMID- 24575463
TI  - Recovery in mental health.

PMID- 24575464
TI  - No sacred cows as private sector embraces society-wide  solutions.

PMID- 24575465
TI  - Universal coverage possible- with private sector support.

PMID- 24575467
TI  - Authors' response.

PMID- 24575468
TI  - Authors' response.

PMID- 24575469
TI  - The authors respond.

PMID- 24575470
TI  - Urethral obstruction in cats.

PMID- 24575471
TI  - [Reply to the critical opinion of Johannes G. Schmidt to the scientific medical
      congress VegMed in 2012 (researchers Komplementmed 2013; 20: 469)].

PMID- 24575472
TI  - [25th anniversary of Nizhny Novgorod State Medical Academy Dental School].

PMID- 24575473
TI  - [Mediation procedure experience in foreign legislation].

PMID- 24575474
TI  - [Antimicrobial photodynamic therapy in periodontology].

PMID- 24575475
TI  - [Phagocytes protection of periodontium and its ways activation].
AB  - In the review of the literature modern data on mechanisms phagocytes protection
      of periodontium, sold monocytes-macrophage system and neutrophil are resulted.
      The opportunity of programming of a morphological amd functional phenotype of
      macrophage is analyzed by change of concentration of whey of blood. Data on
      functioning in gingival sulcus or periodontal pocket << extracellular neutrophil
      traps>> are resulted. Opportunities to operate by the nonspecific protective
      answer of fabrics periodontium on microbic aggression are shown.

PMID- 24575476
TI  - Some Kai Tiaki articles are 'like the Emperor's new clothes'.

PMID- 24575477
TI  - Following the ANZAC nurses.

PMID- 24575478
TI  - Aged-care theme appreciated.

PMID- 24575479
TI  - Rewarding the deserving--the Commo Commendations.

PMID- 24575480
TI  - Responsibility and ethics.

PMID- 24575481
TI  - 'Trusted for our skin colour' in Kolkata's rural slums.

PMID- 24575482
TI  - Working with spinal patients in Samoa.

PMID- 24575483
TI  - A little health care goes a long way in poor Burkina Faso.

PMID- 24575484
TI  - How can we motivate patients to change?

PMID- 24575485
TI  - Constipation: motility and the gut.

PMID- 24575486
TI  - Coping in a pandemic.

PMID- 24575487
TI  - Helping decrease asthma rates in the Kaipara.

PMID- 24575488
TI  - Nurses' role in safety and quality.

PMID- 24575489
TI  - Hunkered down in the short stay unit.

PMID- 24575490
TI  - A glimpse from the other side.

PMID- 24575492
TI  - Campaigning against youth suicide.

PMID- 24575491
TI  - Using darkness to improve practice.

PMID- 24575493
TI  - Finding unity in aged care.

PMID- 24575494
TI  - Nurses' responsibilities in an election year.

PMID- 24575495
TI  - Child health: revisiting the basics of nursing care.

PMID- 24575496
TI  - Nurse education: stimulating fresh thinking.

PMID- 24575497
TI  - Endovascular repair of complex aortic aneurysms.
AB  - BACKGROUND: Surgery for complex aortic aneurysms (thoracoabdominal, juxtarenal
      and pseudoaneurysms) is associated with a high morbidity and mortality rate.
      Branched and fenestrated stent grafts constitute a new technology intended as an
      alternative treatment for this disease. OBJECTIVES: To describe a single-center
      experience with fenestrated and branched endografts for the treatment of complex
      aortic aneurysms. METHODS: We reviewed all cases of complex aortic aneurysms
      treated with branched or fenestrated devices in our center. Data collected
      included device specifics, perioperative morbidity and mortality, re-intervention
      rates and mid-term results. RESULTS: Between 2007 and 2012 nine patients were
      treated with branched and fenestrated stent grafts. Mean age was 73 years. Mean
      aneurysm size was 63 mm. Perioperative mortality was 22% (2/9). During the follow
      up, re-interventions were required in 3 patients (33%). Of 34 visceral artery
      branches 33 remained patent, resulting in a patency rate of 97%. Sac expansion
      was seen in a single patient due to a large endoleak. No late aneurysm-related
      deaths occurred. CONCLUSIONS: Branched and fenestrated stent grafts are feasible
      and relatively safe alternatives for the treatment of complex aortic aneurysms
      involving the visceral segment. Further research is needed to determine the long
      term durability of this new technology.

PMID- 24575498
TI  - Quality of coding diagnoses in emergency departments: effects on mapping the
      public's health.
AB  - BACKGROUND: Emergency department (ED) attendees reflect the health of the
      population served by that hospital and the availability of health care services
      in the community. OBJECTIVES: To examine the quality and accuracy of diagnoses
      recorded in the ED to appraise its potential utility as a guage of the
      population's medical needs. METHODS: Using the Delphi process, a preliminary list
      of health indicators generated by an expert focus group was converted to a query
      to the Ministry of Health's database. In parallel, medical charts were reviewed
      in four hospitals to compare the handwritten diagnosis in the medical record with
      that recorded on the standard diagnosis "pick list" coding sheet. Quantity and
      quality of coding were assessed using explicit criteria. RESULTS: During 2010 a
      total of 17,761 charts were reviewed; diagnoses were not coded in 42%. The
      accuracy of existing coding was excellent (mismatch 1%-5%). Database query
      (2,670,300 visits to 28 hospitals in 2009) demonstrated potential benefits of
      these data as indicators of regional health needs. CONCLUSIONS: The findings
      suggest that an increase in the provision of community care may reduce ED
      attendance. Information on ED visits can be used to support health care planning.
      A "pick list" form with common diagnoses can facilitate quality recording of
      diagnoses in a busy ED, profiling the population's health needs in order to
      optimize care. Better compliance with the directive to code diagnosis is desired.

PMID- 24575499
TI  - Changes in anti-citrullinated protein antibody titers following treatment with
      infliximab for rheumatoid arthritis.
AB  - BACKGROUND: The presence of anti-citrullinated peptide/ protein antibody (ACPA)
      has a high specificity and predictive value for the development of rheumatoid
      arthritis (RA). Some studies have shown decreased titers of this antibody after
      treatment with infliximab. OBJECTIVES: To assess the changes in ACPA titers in
      patients with RA after treatment with infliximab as a first biological agent, and
      to correlate these variations with non-infusion-related adverse effects. METHODS:
      In a prospective multicenter observational study involving 48 research centers,
      we assessed 139 patients with established moderate-to-severe RA diagnosed
      according to American College of Rheumatology criteria. Samples were collected
      before and 6-12 months after treatment. RESULTS: The mean age of the study
      patients was 50.6 years and 118 were female (84.9%). Statistically significant
      variations in ACPA titers were noted in 47 patients (before and after treatment)
      (P = 0.012). Overall, ACPA titers were decreased in 32 (65.3%) and increased in
      15 (34.7%). No correlation was found between severe or mild adverse effects in
      patients presenting variations in ACPA titers. CONCLUSIONS: The present study
      showed that infliximab affected ACPA titers, promoting mainly a decrease;
      however, this was not related to the occurrence of non-infusion-related adverse
      effects.

PMID- 24575500
TI  - Effect of Surgical Safety checklist implementation on the occurrence of
      postoperative complications in orthopedic patients.
AB  - BACKGROUND: Surgical adverse events are errors that emerge during perioperative
      patient care. The World Health Organization recently published "Guidelines for
      Safe Surgery." OBJECTIVES: To estimate the effect of implementation of a safety
      checklist in an orthopedic surgical department. METHODS: We conducted a single
      center cross-sectional study to compare the incidence of complications prior to
      and following implementation of the Guidelines for Safe Surgery checklist. The
      medical records of all consecutive adult patients admitted to the orthopedics
      department at Wolfson Medical Center during the period 1 July 2008 to 1 January
      2009 (control group) and from 1 January 2009 to 1 July 2009 (study group) were
      reviewed. The occurrences of all complications were compared between the two
      groups. RESULTS: The records of 760 patients (380 in each group) hospitalized
      during this 12 month period were analyzed. Postoperative fever occurred in 5.3%
      versus 10.6% of patients with and without the checklist respectively (P = 0.008).
      Significantly more patients received only postoperative prophylactic antibiotics
      rather than both pre-and postoperative antibiotic treatment prior to
      implementation of the checklist (3.2% versus 0%, P = 0.004). In addition, a
      statistically non-significant 34% decrease in the rate of surgical wound
      infection was also detected in the checklist group. In a logistic regression
      model of postoperative fever, the checklist emerged as a significant independent
      predictor of this outcome: odds ratio 0.53, 95% confidence interval 0.29-0.96, P
      = 0.037. CONCLUSION: A significant reduction in postoperative fever after the
      implementation of the surgical safety checklist occurred. It is possible that the
      improved usage of preoperative prophylactic antibiotics may explain the reduction
      in postoperative fever.

PMID- 24575501
TI  - Alkaline phosphatase level change in patients with osteosarcoma: its role as a
      predictive factor of tumor necrosis and clinical outcome.
AB  - BACKGROUND: In osteosarcoma the histological response, measured by the percentage
      of tumor necrosis, constitutes one of the most significant predictive factors,
      with better survival in patients whose tumor necrosis is > or = 90%. OBJECTIVES:
      To determine if the decrease rate of serum alkaline phosphatase (SAP) levels
      during the first month of neoadjuvant chemotherapy could serve as a predictive
      indicator of tumor necrosis and clinical outcome. METHODS: We analyzed the
      medical files of 53 osteosarcoma patients (19 females, 34 males) (median age 16
      years, range 8-24); the disease was metastatic in 12 and localized in the other
      41. RESULTS: The histological responses were good in 38 patients (71.7%) and poor
      in 15 (28.3%). At a median follow-up of 50 months, 34 patients (64.2%) had no
      evidence of disease and 19 (35.8%) had died from the disease. High levels of SAP
      at diagnosis correlated with worse survival (P = 0.002). There was no difference
      in overall survival between patients whose SAP decrease rate was > 25% and those
      with a rate < 25% (P = 0.14). Among female patients, "rapid" SAP responders had
      better survival than "slow" responders (P= 0.026). In patients with metastases
      the SAP decrease rate was positively correlated with survival (P = 0.042).
      CONCLUSIONS: There was no evidence that "rapid" SAP responders had a higher
      percentage of tumor necrosis than "slow" responders, although female "rapid" SAP
      responders had a better prognosis than "slow" responders. Patients with
      metastases at presentation and "rapid" SAP response had better prognoses.

PMID- 24575502
TI  - On-spot rheumatology consultations in a multilevel geriatric hospital.
AB  - BACKGROUND: Musculoskeletal and joint disorders are extremely common in the
      elderly. They directly affect mobility, gait stability, quality of life, and
      independence. OBJECTIVES: To assess the nature of joint problems encountered in a
      geriatric inpatient population and evaluate the contribution of a rheumatologist.
      METHODS: We reviewed the rheumatology consultation records that were conducted in
      a geriatric medical center over a 10 year period. RESULTS: A total of 474
      consultations were held; most of these patients (86%) were hospitalized in the
      acute geriatric departments, 10% in the rehabilitation ward and 4% in the long
      term care wards. Some patients were seen more than once. A rheumatologic joint
      problem was the main reason for hospitalization in 53% of these patients.
      Monoarthritis was the most frequent complaint (50%), followed by pauciarticular
      arthritis (two to five joints) in 30% of patients. Arthrocentesis, diagnostic and
      therapeutic, was performed in 225 patients, most of them in knee joints (81%).
      The most frequent diagnosis was osteoarthritis with acute exacerbation (28%),
      followed by gout (18%), pseudo-gout (9%) and rheumatoid arthritis (9%). In 86
      cases (18%) the diagnosis was a non-specific rheumatologic problem: arthralgia,
      nonspecific generalized pain, or fibromyalgia. CONCLUSIONS: Prompt and
      appropriate evaluation, as well as arthrocentesis and treatment initiation,
      including local injections, were made possible by the presence of an in-house
      rheumatologist.

PMID- 24575503
TI  - Mid-term follow-up after laparoscopic sleeve gastrectomy in obese adolescents.
AB  - BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is gaining credibility as a
      simple and efficient bariatric procedure with low surgical risk. Since surgical
      treatment for morbid obesity is relatively rare in adolescents, few results have
      bten accumulated so far. OBJECTIVES: To prove the safety and efficacy of LSG
      turgery in an adolescent population METHODS: Data were prospectively collected
      regarding adolescent patients undergoing LSG. All patients underwent pre- and
      postoperative medical and professional evaluation by a multidisciplinary team.
      RESULTS: Between the years 2006 and 2011, 32 adolescents underwent LSG in our
      center (20 females and 12males). Mean age was 16.75 years (range 14-18 years),
      mean weight was 121.88 kg (83-178 kg), and mean body mass index 43.23 (35-54).
      Thirty-four comorbid conditions were identified. LSG was the primary bariatric
      procedure in all the patients. Mean operative time was 60 minutes (range 45-80
      min). Tiere were two complications (6.25%): an early staple line leak and a late
      acute cholecystitis. There were no deaths. Mean percent excess weight loss at 1,
      3, 6, 9,12, 24, 36, 48, and 60 months post-surgery was 27.9%, 41.1%, 62.6%,
      79.2%, 81.7%, 71%, 75%, 102.9% and 101.6%, respectively. Comorbidities were
      completely resolved or ameliorated within 1 year folllowing surgery in 82.4% and
      17.6%, respectively. CONCLUSIONS: LSG is feasible and safe in morbidly obese
      adolescents, achieving efficient weight loss and impressive resolution of
      comorbidities. Further studies are required to evaluate the long-term results of
      this procedure as well as its place among other bariatric options.

PMID- 24575504
TI  - Low plasma vitamin D levels and muscle-related adverse effects in statin users.
AB  - BACKGROUND: Treatment with HMG-CoA reductase inhibitors (statins) is often
      complicated by muscle-related adverse effects (MAEs). Studies of the association
      between low plasma vitamin D levels and MAEs have yielded conflicting results.
      OBJECTIVES: To determine if low plasma vitamin D level is a risk factorfor MAEs
      in statin users. METHODS: Plasma levels of 25(OH) vitamin D were measured as part
      of the routine evaluation of unselected statin-treated patients attending the
      coronary and lipid clinics at our hospital during the period 2007-2010. Medical
      data on muscle complaints and statin use were retrieved from the medical files.
      Creatine kinase (CK) levels were derived from the hospital laboratory database.
      RESULTS: The sample included 272 patients (141 men) aged 33-89 years. Mean
      vitamin D level was 48.04 nmol/L. Levels were higher in men (51.0 +/- 20.5 versus
      44.7 +/- 18.9 nmol/L, P = 0.001) and were unaffected by age. MAEs were observed
      in 106 patients (39%): myalgia in 95 (35%) and CK elevation in 20 (7%); 9
      patients (3%) had both. There was no difference in plasma vitamin D levels
      between patients with and without myalgia (46.3 +/- 17.7 versus 48.9 +/- 21.0
      nmol/L, P = 0.31), with and without CK elevation (50.2 +/- 14.6 versus 47.8 +/-
      20.3 nmol/L, P = 0.60), or with or without any MAE (50.4 +/- 15.0 versus 47.8 +/-
      10.2 nmol/L, P = 0.27). These findings were consistent when analyzed by patient
      gender and presence/absence of coronary artery disease, and when using a lower
      vitamin D cutoff (< 25 nmol/L). CONCLUSIONS: There is apparently no relationship
      between plasma vitamin D level and risk of MAEs in statin users.

PMID- 24575506
TI  - Towards endovascular treatment of the entire aorta.

PMID- 24575507
TI  - "Code Blue" for coding discharge diagnoses in the emergency department.

PMID- 24575505
TI  - Athlete's heart in Israel: fact or fiction.
AB  - BACKGROUND: The effects of exercise training on cardiac structure and function
      have been thoroughly investigated in athletes from sport-developed nations; few
      data are available on sportsmen from sport-developing countries. OBJECTIVES: To
      assess the incidence and magnitude of the "athlete heart" phenomenon in an elite
      group of Israeli cyclists. METHODS: An echocardiography study was performed in 56
      cyclists (49 males, mean age 38 +/- 10 years, weekly average training 13.1 +/-
      5.9 hours); 96 sedentary subjects served as a control group. RESULTS: There were
      significant differences in left ventricular end-diastolic diameter (LVEDD)
      between cyclists and the control group (48 +/- 4.7 mm versus 45 +/- 4.1 mm
      respectively, P < 0.001), as well as in inter-ventricular septum (IVS) thickness
      (9.9 +/- 1.2 versus 8.9 +/- 1.2 mm, P < 0.001) and LV mass index (LVMI) (79 +/-
      16 versus 68 +/- 13 g/m(2), P < 0.001). In 5% of the cyclists LVEDD exceeded the
      upper normal limit of 56 mm. In 7% of the cyclists IVS thickness exceeded the
      upper normal limit of 11 mm. LV hypertrophy defined as LVMI > or = 134 g/m(2) was
      absent in the entire cyclist group. CONCLUSIONS: Endurance sport activity in well
      trained Israeli sportsmen results in a modest increment in LV dimensions and LV
      mass. LV dilatation and wall thickness above values compatible with primary
      cardiac disease are rare. These results highlight that in Israeli athletes any
      abnormal echocardiographic value must be thoroughly investigated and not simply
      assumed to be a consequence of sport activities.

PMID- 24575508
TI  - The complexities of anticoagulation in the antiphospholipid syndrome.

PMID- 24575509
TI  - Exercise and fatigue in rheumatoid arthritis.
AB  - Fatigue, the enduring sensation of weakness, lack of energy, tiredness or
      exhaustion, is described by 40%-80% of patients with rheumatoid arthritis as
      their most disabling symptom with wide-ranging consequences for quality of life.
      Little attention has been paid to its multidimensional nature or to its
      reliability as a measure to evaluate progression of the disease. Low impact
      aerobic exercise affects the level of fatigue, and this same level of fatigue
      influences the exercise itself. We searched Medline, Cochrane Collaboration
      Register of Controlled Trials (CCRCT), Lilacs, PubMed and Scopus databases for
      randomized controlled trials (with appropriate description of methods, materials
      and results) on the assessment of fatigue and exercise. Review articles, case
      reports, letters to the editor and editorials were excluded. Of 121 references
      initially identified, 4 randomized controlled trials met the inclusion criteria.
      Two studies used the MAF scale (Multidimensional Assessment of Fatigue), one used
      the MAC (Mental Adjustment to Cancer) fatigue scale, and all trials used POMS
      (Profile of Mood States) to assess fatigue. All four trials conducted a 12 week
      program of two to three times/ week and different periods of follow-up. Two
      studies used low impact aerobic exercise, one used dance-based exercise, and
      another study followed a home cardiopulmonary conditioning program using a
      stationary bicycle. While fatigue appears to be a reliable outcome measure in the
      clinical management of RA, especially when related to exercise prescription,
      further research is needed to evaluate the correlation between exercise, fatigue
      and quality of life, using fatigue scales validated to explore the different
      components of fatigue and its wide-ranging consequences.

PMID- 24575511
TI  - Successful treatment of pure red cell aplasia secondary to chronic lymphocytic
      leukemia using cyclosporine A.

PMID- 24575512
TI  - Manic phenomena in an adult with Prader-Willi syndrome.

PMID- 24575510
TI  - Renal transplantation in a patient with catastrophic antiphospholipid syndrome
      and heparin-induced thrombocytopenia.

PMID- 24575513
TI  - Advocating holism and holistic nursing: AHNA's new adventure.

PMID- 24575514
TI  - Improvisation and the art of holistic nursing.
AB  - The art of improvisation is an essential component of responding on the front
      lines of caring. Improvisation expresses the nurse's capacity to perceive the
      changing patterns of patients and their environments in ways that foster creative
      and innovative approaches to meeting healthcare needs. Many holistic nurses
      across the country are working on the front lines of caring, improvising and
      implementing projects to create change within their communities. This article
      examines improvisation within the context of the art and science of nursing, and
      proposes that improvisation reflects qualities within holistic nursing that are
      essential in contemporary health care.

PMID- 24575515
TI  - Ground zero: holistic care for the first responders of 9/11.
AB  - Holistic nurses bring a dynamic tool box to the front lines of caring. We offer
      specialized clinical knowledge that embodies holistic values, principles and
      therapies. These skills and competencies prepare us to provide the best possible
      holistic care, even in the most unfavorable circumstances.

PMID- 24575516
TI  - Nurturing each other on the front lines of caring: self-care in the aftermath of
      hurricane Sandy.
AB  - Holistic nurses are equipped with a strong set of core values and holistic
      principles that guide our practice. This includes understanding and upholding the
      value of self-care. Even on the front lines in highly stressful situations,
      holistic nurses value the importance of nurturing self and colleagues.

PMID- 24575517
TI  - Phoenix nurses: a path to renewal.
AB  - Sometimes being on the front lines involves caring for our colleagues. "Assisting
      nurses to nurture and heal themselves" is a defined role of holistic nursing
      practice (AHNA & ANA, 2013, p. 8). Nothing can be more catastrophic for a nurse's
      career than the loss of her/his license to practice. In this dark hour a nurse
      will often need extra support and someone to walk alongside her/him in the
      healing process. This article describes a holistic nurse in North Carolina who is
      helping nurses in her region find the courage to rise up from the ashes and start
      anew.

PMID- 24575518
TI  - Caring about community, ecology and the lives of women.
AB  - The front lines of caring extend far beyond U.S. borders. Some holistic nurses
      are using their skill and knowledge to create sustainable change in other
      countries. With the help of her local Vermont community, AHNA member Margarita
      (Rita) Severinghaus is applying the principles and values of holistic nursing to
      improve women's lives in her mother's childhood village in the Dominican
      Republic.

PMID- 24575519
TI  - Grassroots-to-global champions for maternal health.
AB  - Holistic nurses are called to think globally and contribute to the improvement of
      all communities. Often, the front lines of caring are beyond our physical reach,
      yet we can still make a difference by supporting global health both energetically
      and by raising our public voices. The Daring, Caring and Sharing to Save Mothers'
      Lives campaign is one example of holistic nurses who are raising awareness and
      expanding universal consciousness by daring to tell the untold and forgotten
      stories of global health.

PMID- 24575520
TI  - Creating my own healing environment.

PMID- 24575521
TI  - Need to put children's oral health first in Israeli debate on water fluoridation.

PMID- 24575522
TI  - Stakeholder involvement in designing an oral care training package for care home
      staff.
AB  - This paper describes the principles applied and the challenges met while seeking
      user and other stakeholder perspectives before designing an oral care training
      package for carers in nursing and residential care facilities. The public health
      competencies it illustrates include the application of appropriate leadership
      styles, strategic management, collaborative working and knowledge of research
      methodology.

PMID- 24575523
TI  - Promoting oral health of children through schools--results from a WHO global
      survey 2012.
AB  - This paper reviews the range of school-based approaches to oral health and
      describes what is meant by a Health Promoting School. The paper then reports the
      results of a World Health Organization global survey of school-based health
      promotion. Purposive sampling across 100 countries produced 108 evaluations of
      school oral health projects spread across 61 countries around the globe. The
      Ottawa Charter for Health Promotion noted that schools can provide a supportive
      environment for promoting children's health. However, while a number of well
      known strategies are being applied, the full range of health promoting actions is
      not being used globally. A greater emphasis on integrated health promotion is
      advised in place of narrower, disease- or project-specific approaches.
      Recommendations are made for improving this situation, for further research and
      for specifying an operational framework for sharing experiences and research.

PMID- 24575525
TI  - Developing a policy guidance for financing dental care in Iran using the RAND
      Appropriateness Method.
AB  - OBJECTIVE: This study aimed to provide recommendations on health care financing
      with special emphasis on dental care. METHODS: The RAND Appropriateness Method
      was employed to obtain the collective opinion of a multidisciplinary panel of
      experts on a set of recommendation statements regarding Iranian dental care
      financing. An initial set of recommendations were identified from a literature
      review. Panel members, selected purposively and by peer nomination, each rated
      the appropriateness and necessity of the recommendations in a structured process
      of two rounds. Each recommendation was classified as inappropriate, uncertain,
      appropriate but not necessary, or appropriate and necessary according to the
      median rating score and the level of disagreement among the panellists. RESULTS:
      Of 28 initial recommendations, 25 were agreed on as appropriate, of which 22 were
      considered as necessary. Altogether, these recommendations provide a holistic
      picture of an oral health system's financing in three domains: revenue
      collection, pooling of revenues and purchasing of dental services. CONCLUSION:
      The policy guidance recommendations are intended to provide the Iranian oral
      health authorities with an evidence-base for financing dental care. The
      recommendations may be transferrable, at least in part, particularly to
      developing countries with similar hybrid health system structures. Finally, the
      method used to develop the recommendations can serve as a model for use
      elsewhere.

PMID- 24575524
TI  - A five-year evaluation of an NHS dental practice-based specialist minor oral
      surgery service.
AB  - OBJECTIVE: To report the findings of an evaluation of an NHS dental practice
      based minor oral surgery service. BASIC RESEARCH DESIGN: Service evaluation.
      CLINICAL SETTING: NHS specialist practice in England. PARTICIPANTS: Patients and
      referring practitioners. INTERVENTIONS: analysis of activity, patient and
      referring practitioner satisfaction data. MAIN OUTCOME MEASURES: Numbers and case
      mix treated; non-attendance; antibiotic prescribing; complication rates; patients
      and referring practitioner satisfaction. RESULTS: 5,796 treatment appointments
      were arranged, with a median waiting time from receipt of referral to treatment
      of 35 days. Treatment provided included: surgical removal of third molars and non
      third molars, surgical endodontics and other surgical and oral medicine cases
      (28.3%, 53.3%, 3.5%, and 15.0% of cases, respectively). Antibiotics were
      prescribed at 13.1% of all treatment appointments and 2.5% required appointments
      for post-operativecomplications. All but one patient reported overall
      satisfaction and over 98% strongly agreed/agreed with positive attitudinal
      statements about the oral surgeon's communication/information giving, technical
      competence and understanding/acceptance. 70.1% of patients were seen on time and
      under 1% were seen more than 15 minutes late. Some 83.1% felt the standard of
      service was better than expected from a hospital and none felt it was worse. More
      than 85% of referring practitioners agreed that: waiting times were shorter than
      at the hospital; urgent problems were seen quickly; and, the referral process was
      easy and understandable. Over 98% either strongly agreed or agreed that they were
      happy with the service provided. CONCLUSIONS: A range of minor oral surgery
      procedures can be provided with low complication rates, short waiting times,
      acceptable accessibility and high levels of patient and referring practitioner
      satisfaction from a specialist NHS dental practice-based service.

PMID- 24575526
TI  - Professional knowledge of accident and emergency doctors on the management of
      dental injuries.
AB  - BACKGROUND: Accident and emergency (A&E) doctors are often the first to assess
      dental and dento-alveolar injuries. Early diagnosis and appropriate management is
      essential for a good long-term prognosis of restored dental aesthetics and
      function. OBJECTIVE: To evaluate A&E doctors' knowledge of the management of
      dental injuries, and appropriate onward referral. DESIGN AND SETTING: A cross
      sectional survey using a questionnaire sent to A&E doctors of all grades at all
      nine A&E hospitals in South Wales over a consecutive five-month period. METHOD:
      Data relating to the level of knowledge of emergency management of dental trauma
      were analysed. The relationship between doctor's level of experience and previous
      training received on the management of common dento-alveolar trauma was
      considered. Data were analysed for Pearson correlation coefficients. RESULTS: The
      response rate to the questionnaire was 72% (n = 118). There was a negligible
      correlation between the career grade of the doctors and their knowledge of the
      management of dental injuries (r = 0.128, p < 0.001). A strong positive linear
      correlation (r = 0.928, p < 0.001) was found between those with prior training
      and their knowledge of dental injury management. CONCLUSIONS: The findings from
      this study suggest that A&E doctors have only partial knowledge of the management
      of dental injuries, though appropriate training can significantly increase
      knowledge.

PMID- 24575527
TI  - A qualitative evaluation of a Local Professional Network programme "Baby Teeth DO
      Matter".
AB  - OBJECTIVE: The objective of this study was to use a qualitative approach to
      examine the perceptions of dentists who led a health promotion programme entitled
      "Baby Teeth DO Matter". BASIC RESEARCH DESIGN: Semi-structured interviews were
      undertaken with a variety of participants in a health promotional programme
      facilitated by a shadow Local Professional Network. These were then recorded and
      transcribed verbatim. The transcripts were line numbered and subjected to
      thematic analysis to develop a coding frame. Overarching themes were developed
      from the coded transcripts by organising them into clusters based on the
      similarity of their meaning and checked against the coded extracts and the raw
      data. CLINICAL SETTING: General Dental Practice. PARTICIPANTS: General Dental
      Practitioners. INTERVENTIONS: A Greater Manchester-wide prevention programme
      entitled "Baby teeth DO Matter". MAIN OUTCOME MEASURES: To determine the
      perceptions of involved clinicians and whether "clinically owned and clinically
      led" services add value. RESULTS: Eight codes were generated: "Success of the
      project", "Down-stream to up-stream", "Importance of clinically led and
      clinically owned", "Keeping the approach simple", "Importance of networking",
      "Importance of Dental Public Health", "Importance of task and finish" and
      "Threats to the future of the Local Professional Network". These were organised
      into three over-arching themes. CONCLUSIONS: "Clinically Led and Clinically
      Owned" projects appear to empower local practitioners and add value. They
      encourage community-facing practitioners, build capacity and develop personal
      skills;--all in accordance with the fundamental principles of the Ottawa Charter.
      Distributed leadership was seen to be effective and Dental Public Health input,
      "Task and Finishing", resources and clarity of communication were all considered
      to be of critical importance.

PMID- 24575528
TI  - Aesthetic perceptions regarding fluorosis by children from an area of endemic
      fluorosis in India.
AB  - OBJECTIVES: To assess the perceptions of and concerns regarding dental fluorosis
      among 12-15 year-old schoolchildren in an area where fluorosis is endemic and to
      find any association with Tooth Surface Index of Fluorosis (TSIF) scores. BASIC
      RESEARCH DESIGN: A cross sectional study. PARTICIPANTS: 316 children aged 12-15
      years with varying level of dental fluorosis selected from 696 children screened
      for fluorosis. METHODS: The study was undertaken in three villages in rural
      Gadag, Karnataka, India, with fluoride levels in the drinking water ranging from
      2.2 to 4.5 ppm as estimated by the SPADNS spectrophotometric method. Children's
      fluorosis was assessed under natural lighting conditions on the labial surface of
      upper anterior teeth using the TSIF 8-point scale. A self-administered
      questionnaire assessed knowledge, perceptions and concerns. Data were analysed by
      frequency distributions and Spearman's correlation coefficients. MAIN OUTCOME
      MEASURES: Aesthetic perceptions and TSIF scores. RESULTS: The children were aware
      of the fluoride presence and its health effects. TSIF scores correlated with: the
      appearance of front teeth (r = 0.135, p = 0.015); feeling fluorosis would hinder
      smiling (r = 0.116, p = 0.040); feeling distress due to fluorosis (r = 0.111, p =
      0.048). CONCLUSION: Children were aware of fluoride and its health effects. They
      also perceived dental fluorosis as an aesthetic problem.

PMID- 24575529
TI  - Relationship between chewing ability and depressive symptoms.
AB  - OBJECTIVE: Depression, as one of the most common mental health problems, has many
      related factors. Recent studies have suggested chewing difficulties as a risk
      factor for depression in the elderly. This study seeks to investigate whether
      chewing ability is associated with depressive symptoms in a Korean population.
      METHODS: This study used data from the Fifth Korean National Health and Nutrition
      Examination Survey (KNHANES V) conducted in 2010. Self-reported questionnaires
      assessed depressive symptoms and chewing ability for the purposes of this study.
      A total of 6,255 subjects aged over 19 years were included for this study (2,704
      males and 3,551 females). RESULTS: Comparing depressive symptoms with chewing
      ability (i.e., very poor, poor, moderate, good, and very good), the adjusted odds
      ratios (ORs) and confidence intervals (CI) were 1.05 (95% CI: 0.84-1.32) for good
      vs. very good (as a reference), 1.31 (95% CI: 1.00-1.73) for moderate vs. very
      good, 1.41 (95% CI: 1.12-1.78) for poor vs. very good, and 1.76 (95% CI: 1.16
      2.76) for very poor vs. very good. CONCLUSION: This study suggests that subjects
      with reduced chewing ability were more susceptible to having depressive symptoms.

PMID- 24575530
TI  - Caries experience and related factors in 4-6 year-olds attending dental clinics
      in Kinshasa, DR of Congo.
AB  - OBJECTIVES: The aim of this study was to examine the prevalence and severity of
      caries experience (CE) in 4-6 year-olds attending dental clinics in Kinshasa, DR
      Congo, and to explore possible associations with reported behavioural and socio
      demographic factors. METHODS: A convenience sample of children attending five
      dental clinics was recruited. Carers, usually parents, completed a questionnaire
      consisting of socio-demographic information, oral health and tobacco consumption
      profile of parents, socio-economic family situation and oral health habits of the
      child. Children were clinically examined using WHO criteria by trained dentist
      examiners. To investigate factors associated with CE, multivariate logistic
      regression was applied with the significance level set at 0.05. RESULTS: Some 158
      children with mean age 5.3 (sd 0.7) years were recruited; 80% presented with
      clinical signs of CE. Between-meal snacking and drinking was reported by 78% and
      65%; 35% had sugar-containing drinks. Most (81%) brushed once a day and 82%
      brushed in the morning. Prevalence of CE was associated with gender, frequency of
      meals, consumption of drinks during meals and consumption of sugar-containing
      drinks; severity with type of infant feeding and sugar-content of the last meal
      at night. CONCLUSION: The present study shows that both prevalence and severity
      of caries experience were associated with reported dietary habits, confirming the
      importance of preventive interventions dealing with these habits in young
      children living in a developing country.

PMID- 24575531
TI  - Dentists' training and willingness to treat adolescents with learning
      disabilities: the mediating role of social and clinical factors.
AB  - AIM: To test a theoretical model based on Cohen's dental profession factors
      (training; practitioner attitudes; geography) to investigate practitioners'
      willingness to treat adolescents with learning disabilities (LD) in primary
      dental care. PARTICIPANTS: A sample of all 537 primary care dentists working in a
      mainly urban area of Northern Ireland and a more rural area of Scotland. MAIN
      OUTCOME MEASURE: Willingness to treat adolescents with LD. METHOD: Questionnaire
      survey of demographic profile, undergraduate education, current knowledge,
      attitudes towards individuals with LD and willingness to treat this patient
      group. A path analytical approach (multiple meditational model) was used.
      RESULTS: Three hundred dentists participated giving a valid response rate of 61%.
      Undergraduate education and current knowledge (training) strengthened a social
      model perspective promoting positive attitudes and willingness to treat
      adolescents with LD. Undergraduate education and current knowledge about
      disability did not significantly contribute to dentists whose attitudes were
      underpinned by the medical model of disability. Therefore geography (rural or
      urban location) was not an influential factor in willingness to treat adolescents
      with LD. This does not exclude the possibility that area of work may have an
      influence as a consequence of undergraduate university attended. CONCLUSION: This
      model identifies the importance of undergraduate and continuing dental education
      with regard to modifying professional attitudes (social and clinical factors) to
      assist practitioners treat adolescents with LD and provide them with inclusive
      dental services in primary dental care.

PMID- 24575532
TI  - When it comes to the efficacy of metastasectomy, biology is king.

PMID- 24575533
TI  - The 340b drug discount program: oncology's optical illusion.

PMID- 24575534
TI  - Colorectal cancer patients with oligometastatic liver disease: what is the
      optimal approach?
AB  - Although metastatic colorectal cancer is typically incurable, in a good
      percentage of patients (20% to 50%) who have oligometastatic disease confined to
      a single organ-usually the liver-complete metastasectomy can result in cure.
      However, once the decision to pursue surgery is made, there remain a number of
      issues that must be addressed in order to ensure the best possible outcome. These
      include whether to perform synchronous or staged resections of the liver
      metastasis and the primary colon cancer; whether surgery should be performed
      before, after, or in the absence of chemotherapy; if chemotherapy is used, which
      agents will be best; and in patients with locally advanced rectal cancer, whether
      pelvic radiation should be incorporated into the treatment plan. Unfortunately,
      there are limited data that can provide guidance in deciding these questions in a
      particular patient. Here we present the insights we have arrived at through our
      own considerable experience with this patient population, and we reflect on the
      relevant studies that are available.

PMID- 24575535
TI  - In patients with colorectal liver metastases, can we still rely on number to
      define treatment and outcome?

PMID- 24575536
TI  - Perioperative chemotherapy for colorectal cancer liver metastases.

PMID- 24575537
TI  - Neuropathic pain resulting from pelvic masses.

PMID- 24575538
TI  - Cryoglobulinemic disease.
AB  - "Cryoglobulinemia" refers to the presence of cryoglobulins (immunoglobulins that
      precipitate at variable temperatures < 37 degrees C [98.6 degrees F]) in serum.
      Monoclonal cryoglobulinemia (type I) involves a single type of monoclonal
      immunoglobulin, while mixed cryoglobulinemia involves a mixture either of
      polyclonal immunoglobulin (Ig) G and monoclonal IgM (type II), or of polyclonal
      IgG and polyclonal IgM (type Ill); both monoclonal and polyclonal IgM have
      rheumatoid factor activity. Cryoglobulinemia is a unique model of human disease
      for several reasons: (1) cryoglobulins are detected using a simple technical
      approach that is based on in vitro laboratory observation of cold precipitation
      in serum; (2) cryoglobulinemic organ damage may be produced by two different
      etiopathogenic mechanisms (accumulation of cryoglobulins and autoimmune-mediated
      vasculitic damage); and (3) cryoglobulinemia is associated with a wide range of
      etiologies, symptoms, and outcomes, and is considered a disease that combines
      elements of autoimmune and lymphoproliferative diseases. There are three main
      broad treatment strategies in cryoglobulinemia-conventional immunosuppression,
      antiviral treatment, and biologic therapy. Some agents, such as corticosteroids
      and rituximab, have been successfully used in all types of cryoglobulinemia;
      however, treatment should be modulated according to the underlying associated
      disease (chronic viral infections, autoimmune diseases, or cancer), the
      predominant etiopathogenic damage (vasculitis vs. hyperviscosity), and the
      severity of internal organ involvement.

PMID- 24575540
TI  - Cryoglobulinemia: better treatments with brighter outcomes.

PMID- 24575539
TI  - Shining a warm light on cryoglobulinemia.

PMID- 24575541
TI  - In germ cell cancer, are we at the end of the chemotherapy era? Maybe--and we are
      certainly at the end of the RCT era.

PMID- 24575542
TI  - In germ cell cancer, are we at the end of the chemotherapy era? No-targeted
      therapies have not heralded its demise.

PMID- 24575543
TI  - Sequencing of agents for castration-resistant prostate cancer.
AB  - Ten years ago, the clinician treating metastatic castration-resistant prostate
      cancer (CRPC) had palliative options for treatment of symptomatic patients, such
      as the combination of mitoxantrone combined with prednisone, as well as isotope
      therapy. In 2004, docetaxel-based chemotherapy regimens were shown to provide an
      overall survival benefit for patients with CRPC. Today, the prostate cancer
      oncologist is in the enviable position of having six U.S. Food and Drug
      Administration-approved agents to choose from: immunotherapy (sipuleucel-T),
      hormonal therapies (abiraterone, enzalutamide), radiopharmaceuticals (radium
      223), and chemotherapy (docetaxel, cabazitaxel), in addition to agents being
      administered in clinical trials. In general, the sequencing of these drugs is
      based upon the entry criteria from the phase III trials that led to their
      approval. Selection of treatment is based on symptoms, sites of disease (bone vs
      visceral) and types of prior treatment (docetaxel-ineligible vs. pre-docetaxel vs
      post-docetaxel setting). Unfortunately, there is a lack of useful correlative
      biomarkers in prostate cancer to help oncologists select treatment. This problem
      is best illustrated in the post-docetaxel castration-resistant setting, for which
      there are indications to use all five other approved agents. In this review we
      will outline an approach to sequencing these new therapies, with particular
      attention paid to the biology of CRPC.

PMID- 24575544
TI  - Sequencing medical therapy in prostate cancer: not as easy as 1-2-3.

PMID- 24575545
TI  - The success of therapies for metastatic CRPC continues.

PMID- 24575546
TI  - A newly discovered liver mass in a 65-year-old woman.

PMID- 24575547
TI  - Acr appropriateness Criteria management of vaginal cancer.
AB  - Due to its rarity, treatment guidelines for vaginal cancer are extrapolated from
      institutional reports and prospective studies of cervical and anal cancer. An
      expert panel was convened to reach consensus on the selection of imaging and
      therapeutic modalities. The American College of Radiology Appropriateness
      Criteria are evidence-based guidelines for specific clinical conditions that are
      reviewed every 2 years by a multidisciplinary expert panel. The guideline
      development and review include an extensive analysis of current medical
      literature from peer-reviewed journals and the application of a well-established
      consensus methodology (modified Delphi) used by the panel to rate the
      appropriateness of imaging and treatment procedures. In those instances where
      evidence is lacking or not definitive, expert opinion may be used to recommend
      imaging or treatment. Four variants were developed to represent clinical
      scenarios in vaginal cancer management. Group members reached consensus on the
      appropriateness of the pretreatment evaluation and therapeutic interventions.
      This article represents the consensus opinion of an expert panel and may be used
      to inform clinical recommendations in vaginal cancer management.

PMID- 24575548
TI  - To transplant or not to transplant?

PMID- 24575550
TI  - Parental perception of health-related quality of life in children and adolescents
      with short stature: literature review and introduction of the parent-reported
      QoLISSY instrument.
AB  - BACKGROUND: Health-related quality of life (HrQoL) of the child diagnosed with
      short stature is an important outcome to be assessed both from the patient as
      well as from the parental perspective. The objective of this study was to review
      the literature on parent-reported HrQoL and to subsequently develop and
      psychometrically test the parent-reported version of the Quality of Life in Short
      Stature Youth (QoLISSY) instrument for use in clinical and epidemiologic
      research. METHODS: A review of the literature on parental assessment of child
      HrQoL via PUBMED was followed by a psychometric analysis of data collected within
      the European QoLISSY study, in which 686 eligible parents of short statured
      children/adolescents (aged 4-18 years) meeting inclusion criteria participated.
      Patient inclusion criteria were a height below -2 SD, a diagnosis of growth
      hormone deficiency (GHD) or idiopathic short stature (ISS), and treatment status
      in terms of receiving or not receiving recombinant human growth hormone therapy.
      Focus groups eliciting parental HrQoL statements, pilot testing with cognitive
      debriefing, and a field test in 317 parents with a retest in 148 parents were
      conducted simultaneously in France, Germany, Spain, Sweden and the UK. The
      psychometric performance of the parent-reported instrument, developed in parallel
      to the child/ adolescent self-report version, was assessed using standard tests
      of reliability and validity. RESULTS: Literature search failed to identify a
      cross-culturally developed height specific instrument available for both patient
      self-report and parental observer report. Analysis of the QoLISSY focus group
      phase conducted separately in children, adolescents and parents yielded 169 items
      generated from parent focus groups. A cognitive debriefing exercise followed by a
      pilot test of preliminary psychometric characteristics resulted in deleting
      poorly performing items. Field testing of the parent-reported version suggested a
      three-domain core HrQoL structure with 22 items, additional 44 items assessing
      three mediator domains and two parent specific domains. The parent report version
      demonstrated good criterion and construct validity as well as internal
      consistency and test retest reliability. CONCLUSIONS: The QoLISSY parent report
      questionnaire closes a gap in the simultaneous assessment of parent and child
      perception of HrQoL in an international context. It is based on items generated
      from the experience of short statured children, adolescents and their parents and
      is validated for use in five European languages. It is feasible, relevant for
      this population, psychometrically sound and is easy to administer in research and
      clinical settings.

PMID- 24575551
TI  - Is there a link between influenza and type I diabetes? Increased incidence of TID
      during the pandemic H1N1 influenza of 2009 in Chile.
AB  - Pandemic H1N1 2009 had the highest incidence in the middle-high income area of
      Santiago and affected mostly school age patients. Influenza A virus (IAVs) causes
      systemic and most commonly non-systemic infection. Interestingly, it is able to
      replicate only in the presence of trypsin-like enzymes, as lung and pancreas.
      HYPOTHESIS: IAVs infection may trigger beta cell destruction and increase the
      incidence of T1DM. METHODS: A retrospective observational study of new T1DM
      pediatric patients from database of Clinica Las Condes between 1995 and 2012.
      RESULTS: From 58 patients, 44.7% were diagnosed between 2009 and 2010, coincident
      with the H1N1 virus outbreak. There were no differences in clinical neither
      metabolic parameters between those patients from the 2009-2010 period and the
      rest. From those patients with available antibody panel, it was negative in 30%
      of the 2009-2010 group vs. 12.5% of the rest of the cohort (p < 0.05). Only one
      5.8 year old boy had history of H1N1 virus infection three months prior to the
      DM1 onset with negative antibodies. CONCLUSIONS: The temporal coincidence
      suggests a possible link between T1DM and H1N1 virus, might be thought to be
      through direct cytopathic damage. Unfortunately we could only confirm H1N1
      previous infection in only one case. Prospective studies in new T1DM cases are
      necessary to test this hypothesis.

PMID- 24575549
TI  - Measuring growth hormone and insulin-like growth factor-I in infants: what is
      normal?
AB  - The role of growth hormone (GH) and insulinlike growth factor-I (IGF-I) change
      through early childhood. Whereas poor growth is a later presenting feature,
      infants with isolated GH deficiency have a normal birth weight and length, and
      often present with hypoglycemia. IGF-I plays an important role antenatally and
      post-natally in somatic and brain growth. In order to evaluate the GH/IGF-I axis
      in infancy, an understanding of the normal physiology is required. Measurements
      of GH and IGF-I in this population should be interpreted in the context of the
      assays used, as well as their limitations. In this review, we summarize our
      current understanding of normal GH and IGF-I secretion in children under 18
      months of age, and describe variations in the reported assay-specific
      measurements.

PMID- 24575552
TI  - Osteoporosis in thalassemia major: an update and the I-CET 2013 recommendations
      for surveillance and treatment.
AB  - In recent years, the issue of osteopenia/osteoporosis in children, adolescents
      and young adults with thalassaemia major (TM) has attracted much attention
      because it is a prominent cause of morbidity despite adequate transfusion and
      iron chelation therapy. The reported frequency of osteoporosis, even in well
      treated TM patients varies from 13.6% to 50% with an additional 45% affected by
      osteopenia. The pathogenesis of TM-induced osteoporosis is multifactorial.
      Genetic and acquired factors play role in demineralization of bones in
      thalassemia. Osteoporosis is characterized by low bone mass and disruption of
      bone architecture, resulting in reduced bone strength and increased risk of
      fractures. The significant predictors of fracture prevalence include male gender,
      hypothyroidism, age, lack of spontaneous puberty in females, active hepatitis,
      heart disease and diabetes. The early identification of osteopenia and
      osteoporosis is of paramount importance. This is because delayed diagnosis and
      inadequate treatment have led to severe osteoporosis, skeletal abnormalities,
      fractures, spinal deformities, nerve compression and growth failure. dequate
      hormonal replacement, has been posponed, Effective iron chelation adequate
      hormonal replacement, improvement of hemoglobin levels, calcium and vitamin D
      administration and physical activity are currently the main measures for the
      management of the disease. The use of bisphosphonates in TM patients with
      osteoporosis is increasing and their positive effect in improving bone mineral
      density is encouraging. The recommendations of the International Network on
      Growth Disorders and Endocrine Complications in Thalassaemia (I-CET) for
      diagnosis and management of osteoporosis in TM are also briefly included in this
      review.

PMID- 24575554
TI  - [Please enter].

PMID- 24575555
TI  - [A purely material image of mankind].

PMID- 24575553
TI  - Dyggve-Melchiore-Clausen dysplasia (DMC): syndrome associated with a micropenis.
AB  - Dyggve-Melchiore-Clausen (DMC) syndrome is a are autosomal recessive
      spondyloepimetaphyseal dysplasia associated with mental retardation resulting
      from mutations in the Dymeclin (DYM) gene mapped in the 18q12-12.1 chromosomal
      region. We report a case of a consanguineous Moroccan boy with this disease
      confirmed by the presence of homozygous mutation at c.1878delA of DYM gene. Our
      patient additionally has a micropenis. We discuss the clinical severity,
      difficult management of this syndrome and its association with micropenis never
      described before in the literature.

PMID- 24575556
TI  - [Challenging multiplicity in an exciting field of study].

PMID- 24575558
TI  - ["When someone travels..."].

PMID- 24575557
TI  - [Learning to deal with immigrants and differences].

PMID- 24575559
TI  - [Exploring new paths with Master of Science].

PMID- 24575560
TI  - [Every day challenged with innovation].

PMID- 24575561
TI  - [Rehabilitation nursing - no day is like the ones before].

PMID- 24575562
TI  - [Strengthening nursing and continuing development].

PMID- 24575563
TI  - [Nursing also recognized internationally].

PMID- 24575564
TI  - [Urgency of dyspnea in a resident assessed].

PMID- 24575565
TI  - [Dying becomes part of life].

PMID- 24575566
TI  - [Supporting the self efficacy of the patient].

PMID- 24575567
TI  - ["Letting go frees the hands"].

PMID- 24575568
TI  - [There's a first time for everything].

PMID- 24575569
TI  - [The children of Virginia].

PMID- 24575570
TI  - [Quality care - but heavy workload].

PMID- 24575571
TI  - [In the footsteps of nurses].

PMID- 24575573
TI  - [A dialogue to reach agreement ].

PMID- 24575572
TI  - [Cosmetics: the well hidden dangers].

PMID- 24575574
TI  - [A multigenerational association].

PMID- 24575575
TI  - Nephrology as a practice focus.

PMID- 24575576
TI  - Don't sabotage your 2014 job search.

PMID- 24575577
TI  - Chronic kidney disease: new guidelines for the new centrury.

PMID- 24575578
TI  - An integrated approach: hypertension management in patients with chronic kidney
      disease.

PMID- 24575579
TI  - The great pretender: autosomal dominant polycystic kidney disease.

PMID- 24575580
TI  - 2014 job outlook: a bright year spry with legislative wins.

PMID- 24575581
TI  - Relationship between oxidative stress and aortic valve stenosis in humans: an
      immunohistochemical study.
AB  - BACKGROUND: Oxidative stress contributes to plaque formation and the
      destabilization of coronary atherosclerotic lesions. It has been reported that
      disease processes and clinical risk factors of aortic valve stenosis (AS) are
      similar to those of atherosclerosis. In this study, we immunohistochemically
      examined the expression of 4-hydroxy-2-nonenal (4-HNE), an oxidative stress
      related molecule, by using surgically resected aortic valve specimens from AS
      patients. METHODS: The study was conducted using aortic valve specimens,
      surgically obtained from 24 patients with severe AS undergoing aortic valve
      replacement. We immunohistochemically investigated frozen aortic valve samples
      with antibodies against smooth muscle cells, macrophages, CD31 and 4-HNE.
      RESULTS: Morphometric analysis showed that the percentage of the macrophage
      positive area and the number of CD31-positive microvessels were significantly
      higher in AS patients than those in reference cases (macrophages, p < 0.005 and
      CD31, p < 0.0001). Furthermore, the 4-HNE-positive macrophage score was also
      significantly higher in AS patients than in reference cases (p < 0.005).
      CONCLUSIONS: 4-HNE was expressed in the stenotic aortic valves in patients with
      severe AS, suggesting a close relationship between oxidative stress and the
      progression of calcific AS.

PMID- 24575582
TI  - Diagnostic accuracy of transthoracic and transesophageal echocardiography for the
      diagnosis of bicuspid aortic valve: comparison with operative findings.
AB  - BACKGROUND: Bicuspid aortic valve (BAV) is associated with an increased risk of
      aortic valve (AV) dysfunction, aortic dissection, and infective endocarditis.
      Therefore, its accurate diagnosis is critical. The morphological features of AVs
      are generally evaluated by transthoracic echocardiography (TTE) or
      transesophageal echocardiography (TEE), however, the difference in the diagnostic
      capability of these imaging modalities for detecting BAV remains unclear. Here,
      we compared these 2 methods to determine their accuracy, and to clarify each role
      in the diagnosis of BAV. METHODS: This blind study evaluated 126 patients (age,
      70.3 +/- 7.8 years) who subsequently underwent AV replacement. The number of AV
      cusps of each patient was estimated by TTE and TEE and compared to the number of
      AV written in the operative record. Patients with poor echocardiographic images
      were not excluded. RESULTS: Surgical findings showed 97 tricuspid AVs and 29
      BAVs. The sensitivity, specificity, and accuracy for the diagnosis of BAV were
      61%, 81%, and 77%, respectively, for TTE and 86%, 90%, and 89%, respectively, for
      TEE. The accuracy of TEE was significantly higher than that of TTE (p = 0.016).
      In non-calcified AVs, the accuracy of TTE was similar to that of TEE (96%, each)
      whereas in calcified AVs, TTE had a lower accuracy than TEE (72% vs 87%, p =
      0.011). The feasibility was significantly higher for TEE than for TTE (98% vs
      90%, p = 0.003). CONCLUSIONS: TEE provides higher accuracy and feasibility than
      TTE in the diagnosis of BAV, and it should therefore be indicated when
      morphological features of AVs cannot be evaluated by TTE.

PMID- 24575583
TI  - Real-time PCR assays for hepatitis C virus RNA (genotype 1) is useful for
      evaluating virological response to the treatment with peginterferon-alpha2b and
      ribavirin.
AB  - BACKGROUND: The real-time PCR, such as Abbott RealTime assay, have replaced end
      point PCR, such as Amplicor assays, for the measurement of HCV RNA. However,
      'response-guided therapy' to use on-treatment response for tailoring the duration
      of treatment with peginterferon-alpha and ribavirin has not been fully evaluated
      for real-time PCR. METHODS: 43 patients with HCV genotype 1 (24 who had complete
      early virological responses (cEVR) on Amplicor assay and received 48-week
      therapy, and 19 who had late virological responses (LVR) and received 72-week
      therapy) were recruited. Using a RealTime assay, we retrospectively measured HCV
      RNA in stored sera. RESULTS: In 10 samples obtained during therapy, HCV RNA was
      undetectable on the Amplicor assay, but detectable on the RealTime assay. Among
      patients with cEVR on the Amplicor assay, those with detectable HCV RNA on the
      RealTime assay at week 12 were less likely to have a sustained virological
      response (SVR) than those without (2/4 vs 17/20, p = 0.116). Among patients with
      LVR on the Amplicor assay, those with HCV RNA detectable on the RealTime assay at
      week 24 were significantly less likely to have SVR than those without (1/4 vs
      12/15, p = 0.041). CONCLUSIONS: The RealTime assay may be useful for tailoring
      duration of treatment for the patient with HCV genotype 1.

PMID- 24575584
TI  - Relationships between occupational stress and depressive symptoms among prison
      officers in Japan.
AB  - BACKGROUND: The relationships between occupational stress and depressive symptoms
      in prison officers have rarely been studied in Japan. Thus, we analyzed the
      associations between occupational stress factors and depressive symptoms among
      Japanese prison officers. METHODS: This was a cross-sectional study involving 426
      male prison officers (20-60-year-old). Depressive symptoms were assessed using
      the Zung Self-Rating Depression Scale. Using this scale and a cut-off point of
      50, the subjects were divided into the "depressive group" and "non-depressive
      group". Occupational stress was evaluated using the Generic Job Stress
      Questionnaire. Comparisons among the groups were performed with multiple logistic
      regression analysis. RESULTS: Of the 426 subjects, 107 were included in the
      depressive group. After adjusting for demographic and occupational variables,
      higher scores for the physical environment, role ambiguity, and quantitative
      workload and a lower score for social support from co-workers were found to be
      associated with an increased odds ratio of depressive symptoms. CONCLUSIONS: The
      physical environment, role ambiguity, quantitative workload, and social support
      from coworkers are associated with depressive symptoms in Japanese prison
      officers. We hope that educating prison officers about the results of this study
      and organizational/individual-based improvement strategies will reduce their risk
      of depression.

PMID- 24575585
TI  - Histologically proven hepatocellular carcinoma associated with burned-out
      nonalcoholic steatohepatitis.
AB  - A 64-year-old Japanese man was referred to our hospital because of liver
      dysfunction. He had no history of alcohol intake, diabetes, hypertension, and
      hyperlipidemia, and he was negative for hepatitis viral markers. His body mass
      index was 30.6 kg/m2. Homeostasis model assessment of insulin resistance was 6.1.
      Liver biopsy revealed mild steatosis, moderate inflammation, ballooning
      degeneration, and portal fibrosis with bridging fibrosis; on the basis of these
      findings, the diagnosis of nonalcoholic steatohepatitis was made. Thereafter,
      follow-up imaging study was performed every 4 months. At 16 months after liver
      biopsy, a 3 cm hepatic lesion was detected in the right hepatic lobe by computed
      tomography. Dynamic computed tomography revealed a hepatic tumor enhanced with
      contrast medium during the arterial phase and a low-density area during the
      portal phase. Based on the diagnosis of hepatocellular carcinoma, partial
      hepatectomy was performed. Histological examination revealed a moderately
      differentiated hepatocellular carcinoma accompanied by liver cirrhosis without
      steatosis or ballooning degeneration. Finally, the patient was diagnosed with
      hepatocellular carcinoma arising from burned-out nonalcoholic steatohepatitis.

PMID- 24575587
TI  - Reflections and change.

PMID- 24575586
TI  - Postoperative outcomes of primary hepatic neuroendocrine carcinomas: review
      article.
AB  - BACKGROUND: We examined the course of a primary hepatic neuroendocrine carcinoma
      (PHNEC) patient and analyzed the postoperative outcome of all reported PHNEC
      cases. METHODS: A literature search for PHNEC cases was performed using PubMed.
      All reported cases and our present patient were analyzed in this study. Survival
      analysis was performed using the Kaplan-Meier method. Risk factors for the
      recurrence of PHNEC following hepatic resection were investigated. RESULTS: A
      total of 43 patients were analyzed in this study. The 3-, 5-, and 7-year overall
      survival rates were 55%, 48%, and 48%, respectively. The 3-, 5-, and 7-year
      overall survival rates in surgery patients were 78% each, and 25%, 17%, and 17%,
      respectively in nonsurgery patients. Lymph node metastasis posed a significant
      risk factor for postoperative recurrence. CONCLUSIONS: Hepatic surgery is an
      appropriate therapeutic treatment for PHNEC without distant metastasis nor lymph
      node metastasis. Adjuvant chemotherapy might be necessary for PHNEC patients with
      lymph node metastases.

PMID- 24575588
TI  - Health: a complicated calculus.

PMID- 24575589
TI  - It's time to report workplace violence.

PMID- 24575591
TI  - International study tours: an avenue for personal growth.
AB  - This article consists of four integral parts of a complex process leading to
      successful implementation of international study tours. Our role as faculty
      members, in the development of these study tours, began with the proactive,
      reflective practice of examining our cultural experiences, perceptions, and
      understandings of our cultural knowledge, dispositions, and skills. Through these
      tours, educators from other countries and cultures come to The University of
      Montana and experience a collaboration of ideas and acquire a better
      understanding of education in the United States. To be successful these study
      tours need to go beyond content and include a variety of less tangible aspects
      ranging from the Initial Request for Proposals to the culminating activities.
      These study tours have led to the empowerment of educational leaders becoming
      instruments of positive change in their homeland. In turn, the relationships
      developed have transformed the faculty presenters and the institution in ways
      that are both measurable and immeasurable. Human relationships based on mutual
      respect and dignity underlie the success of educational tours.

PMID- 24575590
TI  - Health inequalities: promoting policy changes in utilizing transformation
      development by empowering African American communities in reducing health
      disparities.
AB  - Social inequalities in the United States resulted in negative health outcomes for
      the African Americans. Their stressful living conditions of poverty,
      discrimination, racism, abuse and rejection from American society contribute to
      their negative health outcomes. The lifestyles of African Americans have been
      influenced by poverty and prior injustices, which have molded their worldview of
      health and illness. Dr. Martin Luther King, national civil rights leader, brought
      about social change with much prayer; however, he went a step further with
      collective gatherings to include the power of non-violence massive public
      demonstrations. This paper is an analytical review of the literature addressing
      social inequalities impacting on health inequalities of African Americans
      resulting in health disparities. Policy changes are propose by implementing
      transformation development and community empowerment models as frameworks for
      community/public health nurses in guiding African American communities with
      addressing health disparities. These models empower members of the community to
      participate in a collaborative effort in making political and social changes to
      improve their overall health outcomes.

PMID- 24575592
TI  - Gulf Arab women's transition to motherhood.
AB  - AIM: This paper is a report of the findings of a study of Gulf Arab women's
      perspectives of the transition to motherhood. BACKGROUND: Transition to
      motherhood is a universal phenomenon in which every culture has its own
      expectations and varying supports for women moving through this transition.
      International studies have provided models or categories of maternal responses
      related to cultural aspects of transition to motherhood. However, no known
      research has focused on transition to motherhood among Gulf Arab women. METHOD:
      In the initial cohort seventeen first time Gulf Arab mothers in the United Arab
      Emirates were interviewed during the following three times: before childbirth,
      two-four weeks after childbirth, and forty-days after childbirth. A second cohort
      of seventeen first time new mothers was interviewed after childbirth in Sultanate
      of Oman. FINDINGS: Four patterns were identified as indicators of change as women
      transitioned into motherhood: 1) Women's personal transition: women changed from
      feeling of freedom to feeling of dependency to self-confidence. 2) Mother/baby
      relationships: women changed from fear, anxiety, and uncertainty to feelings of
      care and confidence. 3) Family influences: women experienced family support to
      being integrated and feeling respected by family. 4) Cultural/religious beliefs
      and practices: women felt they were initially observers of culture, to
      experiencing cultural/religious beliefs and practices. This was followed by
      accomplishment in childbearing and childrearing practices. CONCLUSION: As Gulf
      Arab new mothers made the transition to motherhood, four implications for
      international nursing practice emerged: 1) patient teaching to help relieve
      anxiety, fears, and uncertainty, 2) facilitation of mother/baby relationships, 3)
      family-centered care, and 4) the importance of cultural/religious beliefs and
      practices to new mothers.

PMID- 24575594
TI  - A descriptive study in American Samoa: services for people with disabilities.
AB  - State agency service providers of persons with disabilities were surveyed and
      interviewed in American Samoa to describe and understand the level of services
      offered within the federal mandates and cultural context. Responses to the survey
      indicated that a majority of consumers do not request services or complete the
      application forms themselves. The interviews revealed an important aspect that
      was overlooked from the initial stages of the study: Many service providers did
      not have a conceptual understanding of self-determination as defined within a
      western context. We believe this cultural and contextual difference influenced
      how they responded to particular questions and perhaps how they engaged in
      providing services. This preliminary study opens the door for follow up
      investigations to determine the interplay of culture and federal regulations
      coinciding within a Pacific Island population.

PMID- 24575593
TI  - Cultural safety assessment of an urban Canadian hospital.
AB  - Canada continues to grow as a multicultural country but the number of people
      employed in healthcare does not reflect the increasing population diversity. In
      addition there are no set Canadian standards in providing Culturally Safe health
      services. Hence, there may be a lack of safe cultural practices when
      communicating with patients and/or colleagues. The purpose of this survey study
      was to determine if there is inconsistency between the written and practiced
      policy on cultural safety in an urban hospital on the west coast of British
      Columbia. The study examined whether there were any discriminatory practices
      based on diversity as judged by the recipients of the interactions, patients and
      staff. The results indicate that discrimination and equality barriers do exist
      within the hospital even though Canada has equity legislation. The hospital needs
      to adopt policy changes in practice and establish bench marks to create a more
      culturally safe environment through programs and services that meet the diverse
      needs of staff and patients.

PMID- 24575595
TI  - Context, health, and cultural competence: nurse managed health care centers
      serving the community.
AB  - Millions of newly insured people from diverse backgrounds and vulnerable
      communities will seek additional healthcare with the passage of the Affordable
      Care Act. APNs working in federally qualified community-based health care centers
      will need to respond to the challenge of providing integrated health care
      services. APNs approach to practice will need to include principles that address
      social justice, cultural competence, quality assessments, and evaluative
      strategies to ensure effective delivery of care. Shifting patient population
      demographics and the need to strengthen APNs understanding of social-structural
      conditions that limit health and wellbeing will be discussed.

PMID- 24575596
TI  - Cultural differences in family communication about inherited cancer: implications
      for cancer genetics research.
AB  - It is widely accepted that clinical genetic services should provide culturally
      competent service to clients. However, systematic research is needed on the
      cultural meanings of heredity, family cancer, and family communication about
      inherited risk in order to move towards culturally competent cancer genetic
      services. Cultural differences in how families communicate about inherited risk
      is a particularly important, but neglected, research focus. The purpose of this
      paper is to: (1) review extant literature on cultural differences in family
      communication about inherited cancer risk; and (2) provide suggestions for cancer
      genetics research that will ultimately help furnish the evidence base for the
      training and provision of culturally competent cancer genetics services.

PMID- 24575597
TI  - Striking the right balance.

PMID- 24575598
TI  - The national health-care agenda in relation to negative pressure wound therapy.
AB  - The NHS was founded upon the principle of providing health care for all,
      regardless of financial status. However, it has reached a point where patient
      demands are outgrowing NHS resources, causing conflict. Chronic wound management
      represents a considerable financial burden on health services in terms of
      manpower requirement, equipment, specialist opinion, and adjunct therapies, such
      as negative pressure wound therapy (NPWT). Although funding bodies often perceive
      NPWT to be expensive, there is evidence that if used appropriately it leads to
      faster healing, early discharge and better quality of life for patients with
      chronic wounds. However, it must be acknowledged that the type and quality of
      studies are mixed. Further evidence is required to justify the use of NPWT in
      chronic wounds in the primary and secondary health-care setting.

PMID- 24575599
TI  - Wound infection: a clinician's guide to assessment and management.
AB  - Wound infection significantly increases the cost of wound care and has
      significant detrimental effects on patients' quality of life. It is imperative
      that all health-care professionals are able to promptly recognise and assess for
      wound infection and initiate effective management. Clinicians must be able to
      recognise the different levels of bacterial bioburden and to act accordingly.
      This article provides clear guidance for recognising an infected wound,
      understanding the different levels of wound bioburden and practical guidance on
      different forms and appropriateness of antimicrobial agents.

PMID- 24575600
TI  - Self-management of leg ulceration using a compression hosiery kit: considerations
      for service delivery.
AB  - This article describes the experience of a young male who developed leg
      ulceration, which he treated and managed by himself. In an unusual case, with
      with unusual circumstances, he used a leg ulcer hosiery kit as compression
      therapy to sell-manage from the commencement of treatment to healing, with the
      assistance of a remotely based health-care professional. The local NHS and
      private health services that he accessed were unable to provide an appropriately
      tailored service for this patient in full-time weekday employment.

PMID- 24575601
TI  - SSKIN bundle: preventing pressure damage across the health-care community.
AB  - The SSKIN bundle is an evidence-based set of interventions that help to prevent
      pressure damage. This article describes a scientific approach using the Model for
      Improvement (MFI) and a collaborative style of learning to quickly and reliably
      implement the SSKIN bundle across an integrated health-care organisation
      including primary and community care. Teams used the MFI and took a pragmatic
      approach to adapt the SSKIN bundle to make it fit for purpose in many different
      clinical settings. Quick wins, long-term gains and challenges are discussed.
      Ideas for future adaptations of the SSKIN bundle for use in the community are
      offered.

PMID- 24575602
TI  - Juxta CURES: compression for healing venous leg ulcers.
AB  - Clinicians are expected to show improved healing rates, reduction in recurrence
      rates and to demonstrate greater patient satisfaction. All patients should
      rightly expect a high standard of holistic care that supports both their physical
      and emotional needs. Keeping the patient engaged in the "healing process" has
      many beneficial outcomes, not least to their emotional wellbeing. Managing to
      heal the wounds within a realistic timeframe is the required outcome for all
      parties. This article demonstrates how a new compression device, Juxta CURES, has
      a positive impact on patients' quality of life, also benefiting the clinician
      while maintaining cost-saving efficiencies.

PMID- 24575603
TI  - Interview: Annette Downe.

PMID- 24575604
TI  - Experiences: Anthony Kerr.

PMID- 24575605
TI  - Avoidance of inappropriate authorship and self-plagiarism.

PMID- 24575606
TI  - Nurses and heart failure education in medical wards.
AB  - Heart failure is a chronic debilitating disease with significant hospitalisation
      rates. Information and education are foundational elements in making the
      lifestyle changes required for effective self-management of the symptoms of heart
      failure. This paper reports a study of medical nurses' education activities with
      heart failure patients in terms of the topics they addressed and the educational
      resources they found most useful. A random sample of 540 medical ward nurses were
      surveyed in 2009 using a postal questionnaire. The response rate was 47% (234
      medical ward nurses who cared for patients with heart failure). Quantitative data
      were analysed using descriptive statistics, qualitative data through a content
      analysis approach. The majority of respondents (66.7%) cared for patients with
      heart failure several times each week. The total time spent on educational
      activities by most respondents (70.6%) was estimated as 20 minutes or less over
      the hospitalisation. Printed material was the most commonly used education
      resource although 35 respondents also referred to online information and 84
      nurses did not use educational material at all. The most frequent education
      topics discussed were medication, signs and symptoms and general information
      about heart failure. Psychological factors and prognosis information were the
      topics least discussed with patients. Respondent suggestions to improve patient
      access to heart failure information included more printed information in wards
      such as pamphlets in various languages, information about useful websites and
      having key resources available in te reo Maori. The heart failure educator was
      identified as an important resource for both nurses and patients. The study
      highlighted the limited time many respondents spent on educational activities and
      the need for readily available educational resources to optimise patient heart
      failure education opportunities.

PMID- 24575607
TI  - Nurse perceptions of the Diabetes Get Checked programme.
AB  - AIM: The Diabetes Get Checked programme provided a free annual diabetes check to
      people diagnosed with diabetes. The aim of the present study was to ascertain the
      impact this programme had on the practice of nurses; identify factors that nurses
      consider contributed to the success or failure of the programme in their work
      setting; and to elicit nurses' suggestions for future improved management and
      outcomes for people with diabetes. METHOD: An observational study utilising an
      online survey was undertaken. A total of 748 people completed the survey - the
      majority being nurses. Data were analysed descriptively. RESULTS: The Diabetes
      Get Checked programme was shown to have had a substantial impact on the practice
      of nurses, enabling the development of new models of nursing care, improved
      educational levels among nurses (and doctors), improved confidence in the
      management of diabetes, and increased satisfaction in their work. Nurses in the
      study suggested future interventions and programmes designed to support people
      with diabetes. These include implementation of a multi-disciplinary wrap-around
      approach, enhanced case management and self-management, implementing direct
      funding for nurse-led services, and improving population-based approaches such as
      policy changes and social marketing. DISCUSSION: The study sought nurse's
      perspectives with regard to a recently terminated programme designed to provide
      care to people with diabetes. It identified areas that worked well in programme
      implementation and those that could be improved. These findings provide useful
      information for funders and planners developing new programmes designed to
      support people with diabetes.

PMID- 24575608
TI  - Barriers in education of indigenous nursing students: a literature review.
AB  - The poor health status of indigenous people has been identified internationally
      as a critical issue. It is now commonly accepted that the ability to address this
      concern is hindered, in part, by the disproportionately low number of indigenous
      health professionals, including nurses. This paper reports the findings of a
      review of literature that aimed to identify key barriers in the education of the
      indigenous undergraduate nursing students in the tertiary sector, to identify
      strategies to overcome these, and discuss these elements within the New Zealand
      context. A number of health-related databases were searched and a total of 16
      peer-reviewed articles from Canada, U.S.A., Australia and New Zealand were
      reviewed. Key barriers to recruitment and retention and strategies to overcome
      these are presented. Barriers to recruitment included: academic unpreparedness;
      poor understanding of cultural needs; and conflicting obligations, and financial
      constraints. Barriers to retention included lack of cultural and academic
      support, family obligations and financial hardship. Strategies to address
      recruitment barriers included: addressing pre-entry education requirements;
      targeted promotion of nursing programmes; indigenous role models in the
      recruitment process; and streamlining enrolment processes to make programmes
      attractive and attainable for indigenous students. Strategies to address
      retention barriers included: cultural relevance within the curriculum;
      identifying and supporting cultural needs of indigenous students with active
      participation of indigenous staff; engaging communities and funding support. The
      crucial development of partnerships between academic institutes and indigenous
      communities to ensure the provision of a culturally safe, supportive environment
      for the students was stressed. In New Zealand, while government-level policy
      exists to promote the success of MBori nursing students, the translation of what
      is known about the recruitment and retention of indigenous students is an area
      for development.

PMID- 24575609
TI  - Progress on policy.

PMID- 24575610
TI  - Journal beats all opposition.

PMID- 24575612
TI  - Formulating a vision for oral health.

PMID- 24575611
TI  - A strong tradition of dentistry.

PMID- 24575613
TI  - The Street of the Yellow Horse.

PMID- 24575614
TI  - Odontogenic cervico-fascial infections: a continuing threat.
AB  - STATEMENT OF THE PROBLEM: Dental abscesses are common and occasionally can
      progress to life-threatening cervico-fascial infections. Despite medical
      advances, odontogenic cervico-fascial infections (OCFIs) continue to be a threat.
      The potential seriousness of odontogenic infections (Ols), or dental abscesses,
      is frequently underestimated. General dental practitioners (GDPs) in primary care
      face the challenging decision of whether to refer patients to secondary care or
      to manage them in the community. PURPOSE OF THE REVIEW: This paper reviews the
      relevant aspects of Ols that might be helpful to primary care dental
      practitioners in providing a better understanding of the anatomy and pathology
      and aims to assist in clinical decision. METHOD: An up-to-date review of
      literature on OCFIs, highlighting their potential risks with clinical examples.
      RESULTS AND CONCLUSION: Dental abscesses are common and continue to be a major
      cause for emergency hospital admission to oral and maxillofacial surgery
      departments. They occasionally spread to fascial spaces of the neck, potentially
      posing significant morbidity and mortality. GDPs are usually the first point of
      contact and face the challenge of recognising those at risk of developing OCFIs,
      which are potentially life threatening and require urgent referral for hospital
      treatment. We propose a patient care pathway to be used in primary care.

PMID- 24575615
TI  - Results of data gathered at a smoking cessation counselling stand in the Dublin
      Dental University Hospital on Mouth Cancer Awareness Day 2012.
AB  - INTRODUCTION: The addictive aspect of smoking is well acknowledged. Research has
      shown that interventions by healthcare professionals have been shown to be
      effective and that smokers will benefit from smoking cessation counselling
      before, during and after their quit attempts. Dental hygienists, as part of the
      healthcare team, are well positioned to provide this counselling. MATERIAL AND
      METHODS: A questionnaire was completed by patients, staff, students and members
      of the public, during Mouth Cancer Awareness Day 2012 in the Dublin Dental
      University Hospital to assess the prevalence of smoking as well as the history of
      smoking and quit attempts by current and former smokers. RESULTS: The prevalence
      of smoking was lower than the national average. A total of 18.3% of those
      surveyed were smokers, 25% were former smokers, and 68% of the smokers had their
      first cigarette within 30 minutes of waking, indicating high dependence.
      DISCUSSION AND CONCLUSIONS: The majority of the smokers (79%) had attempted to
      quit. Stress was the most common reason for lapsing. The most common reasons for
      smoking cessation were health issues. The public is well disposed to receive
      information regarding smoking and the methods available to quit by healthcare
      professionals on health awareness days such as Mouth Cancer Awareness Day.

PMID- 24575616
TI  - Dental amalgam: is this the end?
AB  - Dental amalgam is a reliable and effective restorative material with a well
      established role in modern dentistry. Throughout the years its mercury content
      and the risks posed to human health were main topics of interest for many
      scientists. This paper offers a review of the scientific literature on the health
      and environmental impact of mercury in dentistry published over the last decade.
      A variety of peer-reviewed, epidemiological and large-scale clinical studies on
      dental amalgam, as well as published reports of professional and governmental
      bodies, were organised thematically and analysed. The most relevant findings of
      the aforementioned literature are reported. No reliance has been placed on
      unpublished work or publicly available opinions that are not scientifically
      based. In order to offer an appropriate view on the topic the toxicology, health
      impacts and possible environmental threats are briefly presented in relation to
      the relevant literature published in the last ten years. It is almost unanimously
      accepted that dental amalgam is a safe material, with little or insignificant
      adverse effect on general health. However, current and mostly unfounded
      environmental concerns may result in the implementation of new across the board
      legislation that could lead to a global dental amalgam "phase out".

PMID- 24575617
TI  - Time to get creative with your advertising.

PMID- 24575618
TI  - [Special issue of Monte Carlo simulation].

PMID- 24575619
TI  - [Medical application of Geant4].

PMID- 24575620
TI  - [EGS5 code, outline and how to start using the code].
AB  - The outline of EGS5 code is described. History, scope (energy range and particle)
      of the simulation, major application of the code is mentioned. Physical processes
      in EGS5 code are described. Procedure to set up of input file and user code for
      new calculation is explained.

PMID- 24575622
TI  - On the features, successes and challenges of selected ion flow tube mass
      spectrometry.
AB  - The major features of the selected ion flow tube mass spectrometry (SIFT-MS)
      analytical method that was conceived and designed for the analysis, in real time,
      of air obviating sample collections into bags or extraction by pre-concentration
      of trace compounds onto surfaces are reviewed. The unique analytical capabilities
      of SIFT-MS for ambient analysis are stressed that allow quantification of
      volatile organic and inorganic compounds directly from the measurement of
      physical parameters without the need for regular instrumental calibration using
      internal or external standards. Then, emphasis is placed on the challenging real
      time accurate analysis of single exhalations of humid breath, which is now
      achieved and readily facilitates wider applications of SIFT-MS in other fields
      where trace gas analysis has value. The quality of the data obtained by SIFT-MS
      is illustrated by the quantification of some exhaled breath metabolites that are
      of immediate relevance to physiology and medicine, including that of hydrogen
      cyanide in the breath of patients with cystic fibrosis. The current status of
      SIFT-MS is revealed by a form of a strengths, weakness, opportunities and threats
      (SWOT) analysis intended to present an objective view of this analytical
      technique and the likely way forward towards its further development and
      application.

PMID- 24575621
TI  - [Features of PHITS and its application to medical physics].
AB  - PHITS is a general purpose Monte Carlo particle transport simulation code to
      analyze the transport in three-dimensional phase space and collisions of nearly
      all particles, including heavy ions, over wide energy range up to 100 GeV/u.
      Various quantities, such as particle fluence and deposition energies in
      materials, can be deduced using estimator functions "tally". Recently, a
      microdosimetric tally function was also developed to apply PHITS to medical
      physics. Owing to these features, PHITS has been used for medical applications,
      such as radiation therapy and protection.

PMID- 24575625
TI  - Identification of Ti clusters during nucleation and growth of sol-gel-derived
      TiO2 nanoparticles.
AB  - In the present work, electrospray ionization mass spectrometry (ESI-MS) was used
      to investigate the titanium clusters present during nucleation and growth of sol
      gel derived TiO2 nanoparticles. Depending on the alkoxide precursor used, Ti
      clusters of different sizes were identified [titanium isopropoxide (TTIP)-11-12
      Ti atoms, titanium butoxide (TTB)-10-11 Ti atoms and titanium tetraethoxide (TTE)
      5-7 Ti atoms]. The Ti-O-Ti backbone/core of the titanium clusters were found to
      be quite stable after formation and do not easily break up into smaller clusters.
      The results of this investigation suggest that these clusters are used as
      building blocks in the growth during the induction period. The h-ratio (n H2O/n
      alcoxide) and the pH were not found to influence the identity of the Ti clusters
      present during nucleation of the growth of sol-gel derived TiO2 nano-particles,
      although the induction period was greatly influenced. The reactivity of the
      alkoxy group are OEt > OPri > OBu. The difference in reactivity of the alkoxides
      is generally believed to be due to the increasing size of the alkoxy group which
      causes sterical hindrance during the nucleophilic substitution reaction.

PMID- 24575624
TI  - Gas-phase and solution studies of three resorcin[4]arene derivatives using
      electrospray time-of-flight mass spectrometry.
AB  - Electrospray ionisation mass spectrometry (ESI-MS) has been used to study the
      relative gas-phase proton and alkali metal (Li, Na, K and Cs) binding affinities
      of three different resorcin[4]arenes using the kinetic method. Collision-induced
      dissociation (CID) was used to study the fragmentation of resorcin[4]arene
      heterodimer sandwich complexes, allowing the relative binding affinity order to
      be established. All the alkali metal cations have the same gas-phase binding
      affinity order with the resorcin[4]arene host molecules. At collision energies of
      > or = 13eV, one of the [resorcin[4]arene+Metal]+, (Metal = Li, Na, K) ions
      fragmented through break-up of the resorcin[4]arene, whilst the other host
      resorcin[4]arene remained intact, causing an apparent change in binding affinity
      at high collision energy. This effect was not observed with caesium, since all
      complex ions dissociated readily under CID by displacement of the caesium cation.
      The binding affinity for the protonated resorcin[4]arenes was found to be
      different from the alkali metal cation binding affinity because of the higher
      proton affinity of the nitrogen-containing resorcin[4]arenes. It is shown that
      resorcin[4]arenes containing an oxazine ring can be converted into a ring-opened
      derivative via an Eschweiler-CLarke reaction in the presence of formic acid. A
      second ring-opening process also occurs, including a hydrolysis reaction that
      results in apparent Losses of 12 mass units from the intact resorcin[4]arene.
      Both these reactions occur in solution before mass spectrometric investigation
      and cannot be achieved by CID. This observation was confirmed by inducing the
      Eschweiter-CLarke reaction in a model benzoxazine compound.

PMID- 24575623
TI  - Signal enhancement in electrospray laser desorption/ionization mass spectrometry
      by using a black oxide-coated metal target and a relatively low laser fluence.
AB  - The electrospray Laser desorption/ionization (ELDI) method is actively used for
      direct sample analysis and ambient mass spectrometry imaging. The optimizing of
      Laser desorption conditions is essential for this technology. In this work, we
      propose using a metal target with a black oxide (Fe3O4) coating to increase the
      signal in ELDI-MS for peptides and small proteins. The experiments were performed
      on an LTQ-FT mass spectrometer equipped with a home-made ELDI ion source. A
      cutter blade with black oxide coating was used as a target. A nitrogen laser was
      used with the following parameters: 337 nm, pulse duration 4ns, repetition rate
      10 Hz, fluence to approximately 700 Jm(-2). More than a five times signal
      increase was observed for a substance P peptide when a coated and a non-coated
      metal target were compared. No ion signal was observed for proteins if the same
      fluence and the standard stainless steel target were used. With the assistance of
      the Fe3O4 coated metal target and a relatively low laser fluence < or =700 Jm(
      2)), proteins such as insulin, ubiquitin and myoglobin were successfully ionized.
      It was demonstrated that the Fe3O4-coated metal target can be used efficiently to
      assist laser desorption and thus significantly increase the analyte signal in
      ELDI-MS. A relatively low laser fluence (< or = 700 Jm(-2)) was enough to desorb
      peptides and proteins (up to 17 kDal with the assistance of the Fe3O4-coated
      metal target under ambient conditions.

PMID- 24575626
TI  - Characterization of the species formed during the extraction of thorium employing
      tri-n-butyl phosphate and N,N-dihexyl octanamide as extractants by laser
      desorption/ionization time-of-flight mass spectrometry.
AB  - Laser desorption/ionization-time-of-flight mass spectrometry (LDI-ToF-MS) has
      been applied to identify and characterize the organic phase species formed during
      the extraction of thorium nitrate by 1.1 M tri-n-butyl phosphate (TBP) and N,N
      dihexyl octanamide (DHOA) solutions in n-dodecane. The aqueous phase thorium
      concentrations (at 4M HNO3) have been suitably chosen to get Loaded organic
      phases with/without third-phase. The extracted species have been characterized
      for the first time using LDI-ToF-MS. The results show feasibility of the use of
      this technique for understanding the extraction mechanisms and third-phase
      formation behavior of different extractants. The different chemical species
      observed using this technique are consistent with those observed by small-angle
      neutron scattering (SANS).

PMID- 24575627
TI  - Study of challenging calcium alkoxides in solution by electrospray ionization
      mass spectrometry (Part 1).
AB  - Electrosprayionization was applied on calcium altkoxides studying the
      mostsuitableoperativeconditions for their detection/identification. To reach this
      aim, calcium methoxide and ethylate were obtained by two different synthetic
      pathways, in order to understand their possible different aggregation states. The
      reaction mixture shows the presence of a supernatant and of a precipitate poorly
      soluble in most organic solvents. The purpose of this preliminary study is to
      understand the qualitative differences between the precipitated species and the
      ones in solution by analyzing both of them with the same analytical method. The
      electrospray ionization (ESI) operating conditions (voltages, temperatures,
      solvents) allow not only the detection of single species but also the study of
      clusters present in solution. Particular attention was paid to establishing the
      role of ESI conditions in the formation of the detected species. Experiments
      performed at different sprayer voltages (1 kV, 2kV, 3 kV and 4 kV) proved that
      ESI does not perturbate the equilibria present in the original solution,
      demonstrating that the technique can be a useful tool to achieve information on
      this class of compounds.

PMID- 24575628
TI  - Study of fragmentation behavior of amadori rearrangement products in lysine
      containing peptide model by tandem mass spectrometry.
AB  - Protein and peptide glycation with reducing sugars through Maillard reaction is
      recognized as one of the most critical and fundamental reactions in food and in
      the human body. Amadori rearrangement products (ARPs) are formed at the initial
      stage of Maillard reaction and then may be converted into intermediate and
      advanced glycation products. We report here that using electrospray ionization
      mass spectrometry (ESI-MS) to directly and rapidly characterize fragmentation
      behavior of ARPs in a Lysine-containing peptide-reducing sugars unambiguously
      model and identify the modification sites in glycated tri- and tetrapeptides.
      Tandem mass spectrometry (MS2) results showthat the sugar moiety was
      preferentially fragmented, whereby the neutral loss of small molecules, such as
      18 Da (-H2O), 36 Da (-2 x H2O), 54 Da (-3 x H2O), 84 Da (-H2O-HCOH) and 162 Da
      from monosaccharide (glucose) moieties and 18 Da, 36 Da, 216 Da, 246 Da and 324
      Da from disaccharide moieties. Among the fragmented ions, (M-84+H)+ of
      monosaccharides and (M-246+H)+ of disaccharides are relatively stable. Further
      multi-stage mass spectrometry (MS3) of (M-84+H)+ for tri- and longer peptides
      displays peptide sequence and glycation sites by providing modified y ions (y*),
      and/or modified b ions (b*) and even a modified a ion (a*). The study is useful
      to monitor and characterize PMTs of glycation in complex protein systems based on
      ESI-MS related techniques.

PMID- 24575629
TI  - Root protein profiles of two citrus rootstocks grown under iron
      sufficiency/deficiency conditions.
AB  - Two citrus rootstocks, one sensitive to iron deficiency (Swingle Citrumelo (SCO))
      and the other tolerant (Carrizo Citrange, (CC)), were studied to characterize
      variation in their root protein profile induced by iron-deficient conditions.
      Plants of both rootstocks were grown in two different soils, one volcanic (v) and
      the other calcareous (c), containing 0% and 10% active Lime, respectively. To
      evaluate the effects of the calcareous soil on the protein accumulation of both
      rootstocks, the root protein profiles (SCc vs. SCv and CCc vs. CCv) were
      characterized by two-dimensional gel electrophoresis, thus obtaining, for the
      first time, a reference map of this previously uncharacterized proteome. A total
      of 219 spots, significantly changed in abundance, were analyzed by high
      performance Liquid chromatography nano electrospray ionization tandem mass
      spectrometry. The identified proteins were classified according to their putative
      function and known biosynthetic pathways. Principal component analysis, comparing
      the four sets of data, indicated that each group clustered together with low
      variance and that CCv and CCc data sets were well differentiated, whereas SCv and
      SCc were similar.

PMID- 24575630
TI  - [Macrobiotics-life in harmony with the universe].

PMID- 24575631
TI  - [Viral infection and hemophagocytic lymphohistiocytosis].

PMID- 24575632
TI  - Quadriceps tendon rupture - treatment results.
AB  - INTRODUCTION: Quadriceps tendon rupture is a rare but rather serious injury. If
      this injury is not promptly recognized and early operated, it may lead to
      disability. This research was aimed at pointing out the results and complications
      of the quadriceps tendon rupture surgical treatment. MATERIAL AND METHODS: This
      retrospective multicentric study was conducted in a group of 29 patients (mostly
      elderly men). Lysholm knee scoring scale was used to evaluate the surgical
      results. The post-operative results were compared in relation to the type of
      tendon rupture reconstructions (acute or chronic), various surgical techniques,
      type of injuries (unilateral or bilateral) as well as the presence or absence of
      comorbid risk factors in the patients. RESULTS: The average value of a Lysholm
      score was 87.6. Excellent and satisfactory Lysholm score results dominated in our
      sample of patients. Better post-operative results were recorded in the group of
      patients without risk factors, in case of a bilateral injury, and in case of an
      acute injury. The best result was obtained after performing the reconstruction
      using anchors, and the worst result came after using Codivilla technique.
      DISCUSSION AND CONCLUSION: Early diagnosis and surgical treatment are an absolute
      imperative in management of this injury. We have not proven that a certain
      surgical technique has an advantage over the others. A comorbid risk factor is
      related to a lower Lysholm score. Despite a few cases of complications, we can
      conclude that the surgical treatment yields satisfactory results.

PMID- 24575633
TI  - [Toxoplasma gondii infection in pregnant women].
AB  - INTRODUCTION: The aim of this study was to determine the percentage of
      seropositive pregnant women, i.e. of pregnant women infected with Toxoplasma
      gondii in order to provide an insight into the risk of developing congenital
      toxoplasmosis in our community. MATERIAL AND METHODS: In the period of two years,
      662 pregnant women from Vojvodina were examined serologically. The enzyme-linked
      immunosorbent assay tests were performed to determine IgM and IgG antibodies
      against Toxoplasma gondii and the complement fixation test was done to detect
      total antibodies against Toxoplasma gondii. RESULTS AND DISCUSSION:
      Seropositivity was determined in 180 pregnant women (27.19%). Of 135 pregnant
      women examined in the routine control in pregnancy, 16.30% were seropositive and
      out of five proven, completely new Toxoplasma gondii intfections, three were
      detected in pregnant women who had undergone the routine check-up for no specific
      symptoms. A detailed analysis of the frequency of seropositive findings in
      relation to clinical diagnoses and the place of residence of pregnant women
      (urban and rural areas) was performed. At the same time, the results from the
      serological reactions were presented, commented and interpreted, and
      recommendations were given for the implementation of additional examinations (eg,
      IgG antibody avidity test) in order to make the accurate diagnosis. CONCLUSION:
      It can be concluded that the occurrence of congenital toxoplasmosis is still a
      problem in our community and that the best prevention is the prompt and adequate
      examination of pregnant women for the presence of Toxoplasma gondii infection.

PMID- 24575634
TI  - [Destructiveness of the perpetrators who have committed crimes and misdemeanors].
AB  - INTRODUCTION: Destructiveness in aggressive behavior is interpreted as having
      many causes, the psychiatric ones being of biological, social and
      psychopathological nature. This study was aimed at examining the differences
      among the perpetrators who have committed crimes and misdemeanors in Bosnia and
      Herzegovina in the period from January 1st, 2003 to December 31st, 2012. MATERIAL
      AND METHODS: This prospective, multicentric study used the following measuring
      instruments: list of general data. Hamilton Rating Scale, the Emotional Profile
      Index with descriptive and multivariate statistical analysis. RESULTS:
      Multivariate regression analysis showed that the following variables were
      significantly associated with violence P=0.001: long treatments OR= 810 (95), CI
      0.770 -1.110], migrations [OR=0.830 (95%), CI = 0.825 -1.125,], depression
      [OR=1.150 (95%); CI=0.790-0.990] and the destructiveness revealed by the
      Emotional Profile Index test. Misdemeanors were significantly related with the
      following variables: P =0.001: father's education [OR=0.910 (95%), CI=0.620
      1.100]; living in a suburb [OR=0.850 (95%), CI = 0.930 -1.25, P<0.001],
      destructiveness [OR= 0.670 (95%), CI= 990-1.210, P<0.001]; incorporation and bias
      on Emotional Profile Index test. CONCLUSION: This study has confirmed the
      increase of destructiveness in aggressive behavior in Bosnia and Herzegovina,
      which is of great medical and legal significance. The study points to the social
      and psychopathological characteristics of aggression in Bosnia and Herzegovina.

PMID- 24575635
TI  - [Incidence of complications of antithrombotic treatment in patients with atrial
      fibrillation].
AB  - INTRODUCTION: Atrial fibrillation increases the risk of ischemic stroke five
      fold, while the application of long-term anticoagulant therapy is associated with
      the occurrence of hemorrhagic complications. The aim of our study was to evaluate
      the incidence of thrombotic and hemorrhagic complications in patients with atrial
      fibrillation during antithrombotic treatment. MATERIAL AND METHODS: The study
      included 504 patients that were administered the primary (n=345) or secondary
      thromboprophylaxis after ischemic stroke (n=159), by applying vitamin K
      antagonists, or the combination of vitamin K antagonists and low-dose aspirin.
      The patients were followed for five months in the period of 24 years from 1988 to
      2012, the total number of patient's years being 1884, at the Clinical Center of
      Vojvodina Thromboembolic and hemorrhagic complications were registered during
      regular check-up examinations. RESULTS AND DISCUSSION: Our results indicate the
      low incidence of thromboembolic complications (0.01 patient per a year), with a
      lower incidence in the vitamin K antagonists group than in the group with the
      combination of vitamin K antagonists and aspirin (0.008 patient per a year versus
      0.01 patient per a year). The incidence of hemorrhagic complications was higher
      in the group with the combined treatment compared to the group treated with
      vitamin K antagonists (0.1 patient per a year versus 0.06 patient per a year).
      The frequency of major bleeding was as low as 0.01 patient per a year and more
      frequent in the group with combined treatment (0.03 patient per a year).
      CONCLUSION: The overall incidence of complications in the study group was 0.08
      patient per a year. The combined antithrombotic treatment increases the risk of
      hemorrhagic complications and affects the severity of bleeding. Oral
      anticoagulant therapy is more efficient in the prevention of ischemic stroke and
      thromboembolic complications in patients with atrial fibrillation.

PMID- 24575636
TI  - [Expression of somatostatin in ischemia of rat brain].
AB  - INTRODUCTION: This study used the immunohistochemical method to follow the
      expression of cytoplasmatic protein somatostanin in the course of ischemia of rat
      brain. The aim of the study was to define all the areas of expression of
      somatostain and to show the protein distribution on the map. MATERIAL AND
      METHODS: All the sections of telencephalon, diencephalon and midbrain were
      studied in resistant, and transitory ischemia, which enabled us to observe the
      reaction of neurons to an ischemic attack or to repeated attacks. RESULTS AND
      DISCUSSION: The results of this study show that there is a difference in the
      reaction between the resistant and transitory ischemia groups of rats, especially
      in the parietofrontal cortex, area amygdaloidea anterior, clastrum, nc. reuniens
      and nc. suprachiasmaticus. The mapping shows the reaction in the structures of
      motor, sensitive and sensory cortex, mostly in the laminae I/Ill and V/VI,
      hippocampus- gyrus dentatus and CA1, CA2, CA3, endopiriform nucleus,
      paraventricular and periventricular nucleus of hypothalamus, corpus
      amygdaloideum, claustrum and caudoputamen. The more primitive sections of the
      brain - rhinencephalon, also showed a reaction, which led us to conclude that
      both newer and older brain structures reacted immunohistochemically. Histological
      data showed that small neurons are most commonly found while the second most
      common are big pyramidal cells of multipolar and bipolar type, with the different
      body shape. CONCLUSION: Our findings have confirmed the results of rare studies
      that dealt with these issues, and offered a precise and detailed map of cells
      expressing somatostanin in the rat brain following ischemic attack.

PMID- 24575638
TI  - [Transfusion management of patients with red blood cell antibodies].
AB  - INTRODUCTION: Red blood cell antibodies may cause a positive result of pre
      transfusion blood compatibility testing (crossmatch test). It can be a problem to
      provide suitable blood units for patients with clinically significant antibodies
      to high-frequency antigens as well as for those with multiple alloantibody
      specificities. This study was aimed at identifying transfused patients in the
      population of South-Backa who had developed clinically significant red blood cell
      alloantibodies. MATERIAL AND METHODS: We analyzed the records of crossmatch
      results and antibody screening performed at the Blood Transfusion Institute of
      Vojvodina during 2012. RESULTS: Antibodies were found in 103 patients: A) 63
      patients with single antibodies: 1) 16 with antibodies of unknown specificity (3
      autoantibodies, 13 alloantibodies); 2) 39 with clinically significant antibodies
      (23 from Rh system (2 anti-C, 2 anti-D, 12 anti-E, 7 anti-c), 4 anti-K, 3 anti
      Fya, 7 anti-Jka, 2 anti-S); 3) 8 with usually not significant antibodies (6 anti
      M, 1 anti-Al, 1 antiC); B) 40 patients developed multiple antibodies: 1) all
      patients had at least one clinically significant antibody from various blood
      group system (44 Rh, 13 Kell, 7 Kidd, 7 MNSs (S, s)); 2) 3 patients had usually
      not significant antibodies (1 Lewis, 2 Lutheran); 3) 3 patients occasionally had
      clinically significant antibody (3 anti-Ytd4) 3 patients had antibodies of
      unknown specificity (2 autoantibodies, lalloantibody). Antibodies detected in the
      majority of patients (65-63.1%) had a specificity of Rh and/or the Kell system.
      CONCLUSIONS: The main goal of pre-transfusion blood compatibility testing is to
      detect clinically significant antibodies. The provision of antigen negative blood
      units for those patients is a special challenge for blood establishments.
      Database with a sufficient number of typed blood donors can help to resolve this
      problem.

PMID- 24575637
TI  - [Injuries in elite athletes in the olympic period from 2008 to 2012].
AB  - INTRODUCTION: Research related to injuries of elite athletes is very demanding in
      comparison to research on injuries in team sports, and therefore, there are a lot
      fewer resources and data on injuries in track and field sports than in other
      sports. MATERIAL AND METHODS. The research included 78 athletes who were the
      members of junior and senior national track and field team of Serbia (34 women
      and 44 men), aged 15 to 32 years. The research was conducted in the official
      training camp for the national selection in Bar (Montenegro) by using a non
      standardized survey research technique, an anonymous questionnaire. Out of the
      total number, 59 athletes reported incidence of injury and 19 athletes were
      without injury over the four-year cycle. RESULTS: The majority of injuries were
      reported on the lower extremities, i.e. in 90.8% (n=158), the upper leg and the
      hamstring muscle having been injured in 99 cases (56.9%) and 61 cases (35.05%),
      respectively. The most common type of injuries were strains (n=74; 42.5%),
      followed by partial ruptures (n=30, 16.3%) and distortion (n=25; 14.4%). The most
      frequent diagnosis was hamstring strain (n=37; 21.3%). DISCUSSION AND CONCLUSION:
      Inadequate procedures related to the extent and intensity of training, without
      prevention of injury, often lead to injuries in athletes. It is necessary to
      carry out continuous educational training, especially for coaches, whose effects
      should be reflected in the introduction of new knowledge and scientific
      achievements in the field of biomechanics, training technology, prevention and
      cure in the field of sports medicine. It is also very important to achieve
      adequate and constant cooperation between sports physicians and athletic clubs.

PMID- 24575639
TI  - [Effects of occupational stress on working ability of patients suffering from
      arterial hypertension].
AB  - INTRODUCTION: The aim of this research was to quantify the presence of
      occupational stressors and to analyze their effects on temporary and permanent
      working ability of workers with arterial hypertension. MATERIAL AND METHODS: The
      research included 817 workers. The study group consisted of 504 workers with
      arterial hypertension without other diseases or disorders, whereas the control
      group was composed of 313 healthy workers. RESULTS: The study group showed a
      significantly higher level of total occupational stress index as well as of the
      stress index related to high job demands, conflicts at work place, underload and
      time limit (p<0.001) compared to the control group. A positive and statistically
      significant correlation between total occupational stress index and systolic and
      diastolic blood pressure was found in the study group. The total level of
      occupational stress over 40 led to a significant increase of systolic and
      diastolic blood pressure in persons with arterial hypertension. The analysis of
      temporary working inability determined a statistically significantly higher level
      of lost workdays per a worker in the study group compared to the controls
      (p<0.001). The average number of lost workdays per a worker in a year in the
      study group increased statistically significantly along with the occupational
      stress index values at their work place (p<0.001). In the study group the number
      of workers eligible for disability retirement over a period of one year was
      significantly higher compared to the controls. The number of workers eligible for
      disability retirement in the exposed group increased statistically significantly
      along with occupational stress index values at their work place. CONCLUSION: The
      results show that occupational stress is a significant factor in the development
      of arterial hypertension and reduction of work ability of exposed workers.

PMID- 24575640
TI  - Electrocardiographic signs of acute myocardial infarction in left bundle branch
      block.
AB  - INTRODUCTION: Acute myocardial infarction is characterized by typical chest pain,
      electrocardiographic changes in terms of lesion and/or myocardial ischemia and
      increased cardiac enzymes. It is often difficult to make diagnosis in the
      presence of non-specific chest pain, the short duration of symptoms and
      electrocardiographic signs of a complete left bundle branch block. LITERATURE
      REVIEW: Many authors have tried to set the electrocardiographic criteria that can
      increase the possibility of correct diagnosis of acute myocardial infarction in
      such situations. The most widely used and recognized criterion is Sgarbossa
      scoring system that includes concordant ST segment elevation > 1 mm ST segment,
      disconcordant denivelation of ST segment > 1 mm in the leads V1-V3 and
      disconcordant ST segment elevation > 5 mm with acceptable sensitivity and
      specificity. In subsequent studies, the sensitivity and specificity increased by
      replacing the third criterion with ST/S ratio < -0.25. CONCLUSION: The knowledge
      of certain electrocardiographic signs in patients with acute coronary syndrome
      and left bundle branch block increases the chances of early diagnosis and the
      possibility of better and timely treatment.

PMID- 24575641
TI  - [Cardiovascular diseases during pregnancy and delivery].
AB  - INTRODUCTION: Nowadays, cardiovascular diseases are the leading cause of maternal
      morbidity and mortality in the current obstetric practice. PHYSIOLOGICALLY
      ADAPTED MECHANISMS OF THE CARDIOVASCULAR SYSTEM IN PREGNANCY: It is normal that
      during pregnancy some physiological adaptive changes of the cardiovascular system
      occur and they may contribute to the deterioration of the clinical cardiac status
      of a patient with preexisting or acquired cardiovascular disease. The most
      prominent adaptive mechanisms include the increase of circulating blood volume,
      decrease of peripheral vascular resistance and decrease of plasma colloid-oncotic
      pressure. MOST FREQUENT DISEASES OF THE CARDIOVASCULAR SYSTEM IN PREGNANCY: Due
      to these changes, pregnant women are prone to tachycardia, palpitations and
      peripheral edema. Maternal counseling is obligatory for each pregnant woman in
      order to decrease the maternal morbidity and mortality. The most important
      predictors of maternal mortality for pregnant women with cardiovascular diseases
      are severity of pulmonary hypertension, hemodynamic significance of valvular
      lesion, cyanosis and functional status in heart failure. Cardiovascular diseases
      in pregnant women may be congenital or acquired. The most frequent congenital
      cardiac diseases are atrial and ventricular septal defects as well as persistent
      ductus arteriosus. These diseases are mainly diagnosed and corrected before the
      pregnancy, or left untreated if hemodynamically insignificant. The most frequent
      acquired cardiovascular diseases during pregnancy include arrhythmias, ischemic
      heart disease, rheumatic mitral stenosis and insufficiency, arterial hypertension
      and aortic dissection. CONCLUSION: In all cases of pregnancy associated with
      cardiovascular diseases, early recognition of cardiovascular disease is crucial,
      as well as correct diagnosis and referral to a tertiary centre equipped for a
      multidisciplinary approach of specialists experienced in high-risk pregnancies
      and deliveries in order to prevent maternal mortality.

PMID- 24575642
TI  - [Comorbidity of chronic heart failure and chronic obstructive pulmonary disease].
AB  - Cardiovascular diseases most frequently coexist with the chronic obstructive
      pulmonary disease (COPD). The studies report on over 10 million patients of
      population suffering both chronic heart failure (CHF) and COPD. Similarity of the
      clinical symptoms and risk factors found in the medical history of patients with
      chronic heart failure and chronic obstructive pulmonary disease often causes
      diagnostic mistakes. At present, medicine has the wide range of diagnostic
      methods. Among them: well taken medical history, chest radiogram, determination
      of the serum concentration of natriuretic peptides, spirometry with bronchial
      reversibility test and many others should be mentioned. The skillfull
      interpretation of their results guarantee the possibility of more effective
      treatment. Pulmonary hypertension constitutes the link between the chronic
      obstructive pulmonary disease and CHF. Although its clinical manifestations are
      not specific and can be partially masked by the symptoms of COPD, the possibility
      of its existance should be taken under consideration in every patient with
      worsening effort toleration or intensification of dysponoea and stable
      spirometric values with the lack of other causes. It should be emphasized that,
      apart from the diagnostic leading to diagnosis of those two conditions in one
      patient, there are also the possible interactions of their concurrent treatment.

PMID- 24575643
TI  - [Parameters of cardiac pacing and effectiveness of defibrillation during
      implantable cardioverter-defibrillator lead implantation to right ventricle
      outflow tract].
AB  - Traditional implantation site for implantable cardioverter-defibrillator (ICD) is
      right ventricular apex (RVA). According to many data, this location ensures low
      enough defibrillation threshold. ICDs are more often implanted in patients with
      impaired left ventricle function, in whom, along with disease progression, the
      need for permanent stimulation develops. Right ventricle outflow tract (RVOT) is
      considered to be a better site for permanent stimulation. The aim of the study
      was to assess acute parameters of an ICD lead implantation to RVOT. These are:
      electrical parameters measured during implantation, defibrillation safety margin
      (DSM) and some acute complications requiring reoperation. MATERIAL AND METHODS:
      The study was retrospective. 113 consecutive patients were included in the study
      (including 19 women, mean age was 60,08 years), who had a single coil ICD lead
      implanted in the clinic from 2008 to 2012. The implantation site was left to the
      physicians' discretion, which resulted in majority of RVOT implantations. Among
      indications to implantation in both groups ischaemic cardiomiopathy with low
      ejection fraction was a main indication. Excluding criteria were: using dual coil
      lead, lack of DSM, device of resynchronization implantation. During implantation
      procedure the following parameters were assessed: R wave amplitude, lead
      impedance, ventricular pacing threshold. DSM was performed according to the
      attached scheme. Analysis included: implantation criteria (primary or secondary
      prevention), demographic and clinical factors, administered anti-arrhythmic
      medications. RESULTS: In 91 patients (80.53% of the population) the lead was
      primarily positioned in RVOT while in 22 patients (19.47%) in RVA. In the
      primarily RVOT group, 50% of ICDs were dual chamber, while in RVA group it was
      36%. There were no statistically significant differences between the groups in
      relation to pacing threshold, lead impedance or R wave amplitude. In 20 patients
      the lead was repositioned from RVOT to RVA and in 3 from RVA to RVOT due to
      inappropriate pacing parameters. DSM was satisfying in all of the patients.
      However, in patients implanted in primary prevention 20% of leads needed
      repositioning. In patients implanted in secondary prevention 25% of leads needed
      repositioning. Due to small patient groups, statistical calculations were not
      feasible in this matter. Complications demanding reoperation were the following:
      1 case of right ventricle perforation, 2 cases of atrial lead dislodgement, 3
      pocket haematomas, 1 ventricular exit block and 1 infection. CONCLUSIONS: Acute
      ventricular pacing parameters of single coil defibrillator leads do not differ
      significantly between RVA and RVOT. Surgical complications in both groups are
      similar, while permanent RVOT stimulation seems to be clinically better. Further
      observation in order to determine long term consequences of implantation in
      different sites seems reasonable.

PMID- 24575644
TI  - [Analysis of P wave duration and dispersion in paroxysmal atrial fibrillation].
AB  - Some findings in standard electrocardiogram (ECG) may be associated with
      paroxysmal atrial fibrillation (AF). The aim of the study was to evaluate P wave
      duration and P wave dispersion (Pdysp) derived from 12-lead standard surface ECG
      in sinus rhythm in patients with history of AF in comparison to control subjects
      without AF and with premature ventricular ectopic beats (PVEB). MATERIAL AND
      METHODS: The study group consisted of 20 patients (pts), 9M. 11F, mean age 47.6
      +/- 5.5 years with paroxysmal AF. The control group consisted of 19 pts, 9M, 10F,
      mean age 46.7 +/- 4.7 years without history of AF with PVEB. All patients in both
      groups were treated with antiarrhythmic drugs. Left atrium dimensions (LA) in the
      transthoracic echocardiographic examinations (TTE) and maximal (P(max)), minimal
      (P(min)) wave duration and P(dysp) in a ECG recordings were analyzed. Pdysp was
      calculated as the difference between P(max) and P(min). RESULTS: ECG analysis
      showed statistically significant differences, study group vs control group in P
      wave duration and P(dysp). We found that in AF group P(max) and P(dysp) were
      significantly greater (125.5 vs. 114.5 ms, p < 0.005 and 59.5 vs 45.4 ms, p <
      0.01, respectively). LA were significantly greater in AF group (43.7 vs 41.8 mm,
      p < 0.05). P(dysp) correlated significantly with P(mex) and LA. CONCLUSIONS: In
      AF patients, P wave duration and P wave dispersion, in other words atrial
      depolarization/repolarization inhomogeneity, were increased. A significant
      positive correlation between P wave dispersion and both Pmax and left atrium size
      were found.

PMID- 24575645
TI  - [The hazards of hospitals and selected public buildings of Legionella
      pneumophila].
AB  - The registered infection and outbreaks of epidemic tend to monitor potential
      reservoirs of Legionella infection. According to the Act of 29 March 2007 on the
      requirements for the quality of water intended for human consumption are required
      to test for the presence and number of Legionella in the water system of
      hospitals. In case of detection of L. pneumophila serogroup 1 (SG 1) or increased
      above normal number other serogroups of bacteria it is necessary to eradicate
      these bacteria from the water system. The aim of this study was to assess the
      degree of contamination of the water supply system of selected public buildings
      and analyze the effectiveness of disinfection methods for the elimination of L.
      pneumophila in hot water systems. MATERIAL AND METHODS: The materials for this
      study were hot and cold water samples which were collected from the water supply
      system of 23 different objects. Enumeration of Legionella bacteria in water
      samples was determined by membrane filtration (FM) and/or by surface inoculation
      methods according to the standards: PN-ISO 11731: 2002: "The quality of the
      water. Detection and enumeration of Legionella" and PN-EN ISO 11731-2: 2008:
      "Water quality--Detection and enumeration of Legionella--Part 2: Methodology of
      membrane filtration for water with a small number of bacteria". RESULTS: L.
      pneumophila was present in 164 samples of hot water, which accounted for 76.99%.
      In all tested water samples L. pneumophila SG 2-14 strains were detected. The
      most virulent strain--L. pneumophila SG 1 was not detected. In examined 23
      objects in 12 of L. pneumophila exceed acceptable levels > 100 CFU/100 ml.
      CONCLUSIONS: The presence of L. pneumophila SG 2-14 demonstrated in all examined
      objects, indicating the risk of infection, and the need for permanent monitoring
      of the water system supply. The thermal disinfection is the most common,
      inexpensive, and effective method of control of L. pneumophila used in examined
      objects, but does not eliminate bacterial biofilm. Disinfection using the filters
      stopped of L. pneumophila, and was the method of complementary thermal
      disinfection. Chlorine dioxide is a very effective biocide for large numbers of
      L. pneumophila in water systems.

PMID- 24575646
TI  - [The effect of standard kinesiotherapy combined with proprioceptive neuromuscular
      facilitation method and standard kinesiotherapy only on the functional state and
      muscle tone in patients after ischaemic stroke].
AB  - The ischemic stroke is a disease of the central nervous system. Up until today
      there have been very few scientific findings concerning the most effective
      methods of patients rehabilitation. The authors of this article present two
      groups of patients after ischemic stroke who were rehabilitated with use of the
      following methods: kinesiotherapy combined with PNF (proprioceptive neuromuscular
      facilitation) method and kinesiotherapy only. The aim of this study was to assess
      the impact of kinesiotherapy only and PNF method combined with kinesiotherapy on
      the functional state and muscle tone in patients after ischaemic stroke. MATERIAL
      AND METHODS: The study involved a group of 30 patients after ischaemic stroke.
      Patients were divided into two groups, each of them comprising 15 people. Group I
      was rehabilitated with the use of kinesiotherapy exercise and group II with the
      use of kinesiotherapy exercise combined with PNF method. To evaluate the patient
      before and after rehabilitation muscle tone Asworth scale was used and to assess
      functional status Rivermed Motor Assessment (RMA) scale was used. RESULTS: Both
      in group I and II an improvement in muscle tone and functional status were noted.
      Better results were observed in group II in which patients were rehabilitated
      with the use of kinesiotherapy exercise combined with PNF method. All results in
      group I and II displayed a statistically significant improvement in functional
      status and muscle tone. CONCLUSIONS: The use of the classical kinesiotherapy only
      had a noticeably smaller impact on improvement of functional status and muscle
      tone in patients from group I than the use of both: classical kinesiotherapy and
      PNF method which were employed in group II.

PMID- 24575647
TI  - [Social exclusion and discrimination of chronically mentally ill people in the
      Lodz region].
AB  - Mental crisis exerts a negative effect on somatic, psychological and social
      functioning of a mentally ill person. Mental disease is often accompanied by
      factors increasing the social exclusion and discrimination of patients. Another
      problem is deeply rooted stereotypes and prejudices functioning in the public
      opinion, according to which people who suffer from mental disorder are considered
      insane and often dangerous for society. In Poland, thanks to, amongst others, the
      ESF (The European Social Fund) funds, it is possible to finance and implement
      research concerning social exclusion and discrimination of people who have
      experienced a mental crisis. The aim of the study was to evaluate the level of
      social exclusion and discrimination of people suffering from mental disorders
      from the Lodz region on the basis of seven points scale assessing their personal,
      occupational, and social functioning. MATERIAL AND METHODS; The study included a
      group of 101 patients with mental disorders. Participants were selected randomly
      from mental health institutions from the region of Lodz. To evaluate the problem
      of social exclusion in the group of patients a interview questionnaire was used.
      RESULTS: Social exclusion concerned people suffering from schizophrenia and
      psychosis, more than six years of illness, those with allocated disability
      pension, non-working and non-learning, with the lowest levels of education and
      maintaining a one-person household or living with one parent. Those who
      experienced the lowest degree of social exclusion were mainly people suffering
      from mood disorders, people with higher education, learning and working, living
      with both parents. Groups experiencing discrimination were mostly people with
      schizophrenia, disorders due to psychoactive substances, those with secondary and
      professional education, patients having a certificate of disability and
      maintaining a one-person household. CONCLUSIONS: Social exclusion of mentally ill
      people was mainly related to their low education, civic, social and economic
      activity. The problem of discrimination concerned 17% of the tested group. Half
      of participants of the study did not experience the discrimination effect.

PMID- 24575648
TI  - [Leptospirosis--disease with many faces].
AB  - Leptospirosis is a zoonotic disease of global reach caused by pathogenic
      spirochetes of the genus Leptospira. The disease has two periodic phases (septic
      and immune phase) and its clinical manifestations are diverse. Central nervous
      system involvement in leptospirosis most commonly occurs as aseptic meningitis,
      often asymptomatic, only with abnormal cerebrospinal fluid findings. Weil's
      syndrome is defined as liver damage with acute renal failure and bleeding
      diathesis, has a high mortality rate. A pulmonary form may occur as an acute
      respiratory distress syndrome. The reference standard assay is the microscopic
      agglutination test. A titer of at least 1:400 in the presence of symptoms
      confirms the diagnosis. The prognosis depends on a rapid identification and
      treatment with antibiotics. The paper presents selected cases of leptospirosis
      with its different clinical manifestations. The common feature was a severe
      illness and sometimes the need for cooperation of doctors of various
      specialities.

PMID- 24575649
TI  - [Prosopagnosia--a case report].
AB  - Face recognition plays a key role in initiation and coordination of social
      interactions. Face is a source of many valuable information about sex, age,
      health and emotional state of another person. Face perception is also considered
      as the best developed component of human visual perception. The term
      prosopagnosia means the inability to recognize faces previously known, while
      still remaining the ability to correctly identifying other objects from the
      surroundings. This dysfunction can affect face recognition of famous people,
      family members or even own face. Affected person correctly names the object
      (knows, that he deals with the "face"), properly assess the emotional expression
      of a second person, adequately identifies the sex and age of observed person, but
      cannot determine who the person is. The aim of this study is to present a case of
      a patient complaining about emotional dysfunctions and presence of prosopagnosia
      symptoms following neurosurgery for arteriovenous malformation in the right
      temporal lobe.

PMID- 24575650
TI  - [Modern threats and burden of respiratory system diseases in Poland].
AB  - Polish population according to the National Census of Population and Housing,
      which was conducted in 2011, was 38 511.8 thousand. The average life expectancy
      in Poland is 71.0 years for men and 79.7 years for women. The reason for
      hospitalization in Poland are primarily cardiovascular disease (18%), tumors
      (11.4%), digestive diseases (10.6%), respiratory (9.3%), trauma (9.1%),
      infectious diseases (2.3%) and others (39%). Mortality rates determined on the
      basis of the analyzes and simulations in different disease groups indicates that
      the predominant causes of death of Polish citizens are strongly cardiovascular
      disease and cancer. Respiratory diseases occupy fourth place. World analyses
      clearly show that the number of deaths in 2030 due to lung diseases will be the
      fourth (COPD), fifth (pneumonia) and sixth (lung cancer) cause of death. As it
      turns out, the existence of various pathologies affecting the country's economic
      status. Respiratory allergies are observed more often, including in approximately
      20% of Europeans are symptoms of allergic rhinitis (15-20% severe) and in 5-11%
      are diagnosed with asthma. Malignant tumors are the second most common causes of
      death in the group with the highest risk of life for the residents of Polish,
      particularly for men, is lung cancer, because of which in 2001, 20 570 people
      died. Incurred costs of the social security system are mainly caused by
      inflammatory diseases of the respiratory system, which corresponds to the number
      of days of sick leave, especially in the age group 19-28 years, with a decrease
      in the age group above 59 years of age. Numbers hospitalized for respiratory
      diseases according to data from the National Health Fund also clearly indicate
      the cause of inflammation and cancer, and in the population aged 41-60 years, the
      need for hospital treatment is multiplied. The data indicate the constant threat
      of respiratory diseases.

PMID- 24575651
TI  - [Chemotherapy induced peripheral neuropathy].
AB  - Modern cancer therapy prolongs patients life but commonly increases incidence of
      treatment-related complications. One of such adverse effect is a neurotoxicity,
      which usually manifestates as peripheral neuropathies (CIPN), characterised by
      various sensory (tingling, numbness, pain), motor (foot and hands drop, fastening
      buttons difficulties) and autonomic (constipation, arythmia) abnormalities as
      well as pain. Despite of intensive epidemiological and clinical studies,
      standardized diagnostic criteria and methods of the neuropathy prevention and
      treatment have not been fully established. The most commonly used form of
      treatment is symptomatic therapy, including anticonvulsant and antidepressant
      drugs. Proper education of patients and their families of symptoms and neuropathy
      consequences is desirable to reduce anxiety and stress.

PMID- 24575652
TI  - [Contemporary diagnosis and therapy in women with congenital adrenal
      hyperplasia].
AB  - Congenital adrenal hyperplasia (CAH) is an autosomal recessive defect in
      steroidogenesis, mostly affecting 21-hydroxylase enzyme deficiency. The other
      seldom cortisol synthesis abnormalities include deficiencies of: 11beta
      hydroxylase, 3beta-hydroxysteroid dehydrogenase, 17beta-hydroxylase, 17,20-lase
      and 11 beta-hydroxysteroid dwehydrogenase type 1. There are three main types,
      depending on the clinical level of 21-hydroxylase deficiency: (1) classical form-
      salt-wasting CAH (2) the classical form non- salt-wasting (3) non-classical form.
      CAH incidence is estimated at 1/14 000-1/10 000, of which about 70% is the
      classic salt-wasting form. The clinical picture varies considerably depending on
      the form. In the classic salt-wasting CAH may develop into the a shock. In
      classic CAH without loss of salt dominates virilization in girls and precocious
      puberty in boys. A non-classical forms usually presents as hyperandrogenisation
      and fertility. CAH treatment is mainly based on the use of glucocorticoid
      therapy, and if necessary supplemented mineralocorticoids. There is also
      potential to consider prenatal treatment (female fetuses diagnosed as CAH) with
      the use of dexamethason. However this kind of treatment is related to some
      medical and ethical controversies.

PMID- 24575653
TI  - [Diabetes mellitus-related oxidative stress and its parameters in saliva].
AB  - The uncontrolled accumulation of glucose and fatty acids in the human body
      without the possibility of any cells utilizing them as metabolic substrates is a
      typical occurrence in the process of diabetes mellitus. High concentration of
      mentioned substances leads to oxidative stress and that reasons in numerous
      complications as a result of diabetes which are often demonstrated in the oral
      cavity as periodontal inflammations. There are many ways to study the biomarkers
      of oxidative stress such as: superoxide dismutase (SOD), catalase, glutathione
      peroxidase, glutathione reductase, glutathione, vitamins, lipid peroxidation,
      concentration of nitrites, non-enzymatic glycosylation of proteins and
      hyperglycaemia in diabetes. Considering the attainability and simplicity required
      to collect, saliva is a popular research material used to test these biomarkers.

PMID- 24575654
TI  - [Current attitudes to the elimination of infection foci from the oral cavity of
      adult patients qualified for allogeneic hematopoietic stem cell transplantation].
AB  - Oral cavity is often the source of local and/or general complications in patients
      treated by allogeneic hematopoietic stem cell transplantation (alloHSCT).
      According to the literature dental treatment of an adult patient prior to
      transplantation is based on empiric protocols elaborated by oncological clinics
      for their individual needs. Suggested rules often differs between each other. I
      this article we present different attitude to the important problem of either
      removing or leaving the potential dentogenic foci of infection. The analysis of
      the literature suggest that the most appropriate procedure is to eliminate all
      potential and existing sources of infection before transplantation, as long as it
      is possible by the amount of time remaining before beginning the conditioning
      chemo/radiotherapy and by the general condition of a patient. In another case
      dental treatment should be postponed until the posttransplantation period.

PMID- 24575655
TI  - [Phytotherapy threats with emphasis on St. John's wort medicines].
AB  - Plant medicines used by patients in self-treatment contain powerfully acting
      active substances which can be a source of adverse events including interactions
      with synthetic medicines. Usage of St. John's wort causes high risk of various
      complications. St. John's wort preparations shouldn't be combined with
      antidepressants without physician's consultation. Long-term intake of medicines
      which contain Hypericum perforatum extracts can be a reason of undesirable
      interactions with isoenzymes CYP3A4, CYP1A2, CYP2C9, CYP2C19 and P-glycoprotein
      (P-gp) for which St John's wort is a substrate. Compounds present in the St.
      John's wort, especially hyperforin, increase the activity of cytochrome P450 in
      the liver and intestinal mucosa as well as P-gp, which can accelerate their
      elimination from the body, decrease their concentrations and reduce the effect.
      Effective and safe phytotherapy requires a lot of knowledge about the properties
      and toxicity of preparations used and accurate monitoring of the consequences of
      their actions.

PMID- 24575656
TI  - [Factors influencing self-perception of overweight people].
AB  - Shaping of self-perception is among others influenced by physical, interpersonal,
      emotional, and cultural factors. In self-perception of overweight people an
      important role is played by interpersonal factors, which include the opinions of
      others and the relationship with the surrounding. The evaluation of the body
      image is also affect by sociocultural factors including the media, which create
      an unrealistic and impossible to achieve ideal of beauty. Contemporary ideal of
      beauty, where a slim figure is dominant, more frequently contributes to the
      occurrence of discrimination and stigmatization of overweight people. This
      phenomenon causes negative self-perception leading to the occurrence of such
      emotional problems as low self-esteem, lack of confidence, depression and anxiety
      disorders. Overweight children and adolescents are also frequently stigmatized
      and discriminated because of their body weight, which results in the development
      of a negative body image that may lead to low self-esteem and symptoms of
      depression.

PMID- 24575659
TI  - [Formulation of multiparticular drug delivery systems by compressing pellets into
      tablets].
AB  - The use of multiparticulate drug delivery systems can contribute to more
      efficient and safe therapy while stability and incompatibility problems can be
      avoided as well. The aim of the present work was to review the possible ways of
      production of pellets containing multiparticulate units and studying the most
      important factors influencing the product quality attributes after tablet
      compression. The relationship between the formulation variables (compression
      pressures, different amounts of tableting excipients) and the dissolution profile
      of the gastroresistant coated beads were investigated.

PMID- 24575657
TI  - [Importance of drug interactions with smoking in modern drug research].
AB  - Drug interaction is a process during which a drug's fate in the body or its
      pharmacological properties are altered by an influencing factor. The extent of
      the drug interaction's effect can vary. The interaction could result from the
      modulation by another drug, food, alcohol, caffeine, narcotics, a drug
      influencing absorption or smoking. Moreover, transporter interactions with
      smoking could also have a major impact on many drug's efficacy. Clinically
      relevant drug interactions with smoking were classified in terms of their effect:
      pharmacokinetic, pharmacodynamic and transporter interactions. Policyclic
      aromatic carbohydrates, found in cigarette smoke, have enzyme inducing
      properties. The interaction affects mainly the hepatic isoenzyme CYP1A2.
      Interactions caused by smoking have an effect on all drugs being substrates of
      and therefore metabolised by CYP1A2. Pharmacokinetic alteration can also occur
      during the absorption, distribution and elimination process. The pharmacodynamic
      interactions are mainly caused by the effects of nicotine, a cigarette smoke
      component. Through interactions, smoking could also modify the activity of
      transporter proteins, altering this way the ADME properties of many drugs. Since
      smoking is one of the deadliest artefact in the history of human civilisation,
      identifying drug interactions with smoking is the physician's and pharmacist's
      major responsibility and task. Moreover, it is necessary to identify the
      patient's smoking habits during a medical treatment. This review aims to
      investigate the main types of drug interactions (PK/PD), identify factors
      influencing the activity of CYP enzymes and transporters, and also summarize the
      mechanisms of the most important drug interactions with smoking and their
      clinically relevant consequences (Table II-VI.). Drugs, with effects somehow
      altered by smoking-interactions, have been studied.

PMID- 24575660
TI  - [Application of Kohonen Self-Organizing Feature Maps in QSAR of human ADMET and
      kinase data sets].
AB  - QSAR predictions have been proven very useful in a large number of studies for
      drug design, such as kinase inhibitor design as targets for cancer therapy,
      however the overall predictability often remains unsatisfactory. To improve
      predictability of ADMET features and kinase inhibitory data, we present a new
      method using Kohonen's Self-Organizing Feature Map (SOFM) to cluster molecules
      based on explanatory variables (X) and separate dissimilar ones. We calculated
      SOFM clusters for a large number of molecules with human ADMET and kinase
      inhibitory data, and we showed that chemically similar molecules were in the same
      SOFM cluster, and within such clusters the QSAR models had significantly better
      predictability. We used also target variables (Y, e.g. ADMET) jointly with X
      variables to create a novel type of clustering. With our method, cells of loosely
      coupled XY data could be identified and separated into different model building
      sets.

PMID- 24575661
TI  - Recumbent height measurement among older adults.

PMID- 24575658
TI  - [Development and biochemical characterization of EGFR/c-Met dual inhibitors].
AB  - The epidermal growth factor receptor (EGFR) family has been well-known for more
      than ten years as the target of non-small lung carcinoma (NSCLC) which is one of
      the leading cause of mortality among the cancer types. The receptor tyrosine
      kinase inhibitors (gefitinib, erlotinib, lapatinib) which have been applied in
      the therapy, are not able to inhibit the progression of this disease perfectly
      because of resistance. It has been demonstrated that the amplification of
      mesenchymal-epithelial transition factor (c-Met) or secondary mutation of EGFR
      kinase causes the resistance against EGFR inhibitors in 18-20 percent of the
      cases. Clinical candidates inhibiting both of EGFR and c-Met kinases are unknown
      in the literature. We have developed quinoline-based inhibitors in our research
      project, which inhibit both kinases in submicromolar range in enzymatic assays,
      moreover we have demonstrated by western blot analysis that these compounds
      inhibit the autophosphorylation in vivo. The binding of the effective compounds
      was examined by in silico and docking simulations.

PMID- 24575662
TI  - Development of a local malnutrition risk screening tool-hospital (MRST-H) for
      hospitalised elderly patients.
AB  - INTRODUCTION: Hospitalised elderly patients are at high risk of malnutrition due
      to the presence of chronic diseases and inadequate food intake. It was on this
      premise that a Malnutrition Risk Screening Tool-Hospital (MRST-H) was developed
      for identifying the risk of malnutrition among Malaysian elderly patients.
      METHODS: A total of 181 respondents aged 65 years and above who had been admitted
      to the Geriatric Ward of the University Malaya Medical Centre were recruited. The
      respondents' nutritional assessment was assessed using the Global Indicator of
      Malnutrition (GIM), a reference gold standard of malnutrition consisting of
      anthropometric measurements, biochemical indicators and the Subjective Global
      Assessment (SGA). Important predictive factors of malnutrition were determined by
      logistic regression analysis. RESULTS: Five out of 18 predictive factors were
      significantly associated with malnutrition (p<0.05) in the final multivariate
      logistic regression model. These five factors were used to develop the MRST-H.
      Its validity was tested among 100 elderly inpatients in the Kuala Lumpur
      Hospital. The MRST-H was found to have 66.7% sensitivity, 96.2% specificity and
      82.4% positive predictive value to GIM. The MRST-H was tested for reliability
      among 40 patients involving three raters (a dietitian and two nurses). The Kappa
      index of agreement was excellent between the dietitian with nurse A (81.3%,
      Kappa=0.84) and nurse B (87.5%, Kappa=0.89) respectively. CONCLUSION: The MRST-H
      developed showed high validity and reliability as a screening tool for
      identifying hospitalised elderly patients with high risk of malnutrition.

PMID- 24575663
TI  - Development of demi-span equations for predicting height among the Malaysian
      elderly.
AB  - INTRODUCTION: This study aimed to develop demi-span equations for predicting
      height in the Malaysian elderly and to explore the applicability of previous
      published demi-span equations derived from adult populations to the elderly.
      METHODS: A cross-sectional study was conducted on Malaysian elderly aged 60 years
      and older. Subjects were residents of eight shelter homes in Peninsular Malaysia;
      204 men and 124 women of Malay, Chinese and Indian ethnicity were included.
      Measurements of weight, height and demi-span were obtained using standard
      procedures. Statistical analyses were performed using SPSS version 18.0. RESULTS:
      The demi-span equations obtained were as follows: Men: Height (cm) = 67.51 +
      (1.29 x demi-span) - (0.12 x age) + 4.13; Women: Height (cm) = 67.51 + (1.29 x
      demi-span) - (0.12 x age). Height predicted from these new equations demonstrated
      good agreement with measured height and no significant differences were found
      between the mean values of predicted and measured heights in either gender
      (p>0.05). However, the heights predicted from previous published adult-derived
      demi-span equations failed to yield good agreement with the measured height of
      the elderly; significant over-estimation and underestimation of heights tended to
      occur (p>0.05). CONCLUSION: The new demi-span equations allow prediction of
      height with sufficient accuracy in the Malaysian elderly. However, further
      validation on other elderly samples is needed. Also, we recommend caution when
      using adult-derived demi-span equations to predict height in elderly people.

PMID- 24575664
TI  - Bone health status and lipid profile among post-menopausal malay women in Cheras,
      Kuala Lumpur.
AB  - INTRODUCTION: A cross-sectional study was conducted to determine bone health
      status and nutrient intakes among post-menopausal women residing in low cost
      houses in Cheras, Kuala Lumpur. METHODS: A total of 125 subjects aged 60 +/- 4
      years who had attained menopause at age 50 +/- 5 years participated in this
      study. Subjects' weight and height were measured and calculated for body mass
      index (BMI). They were also assessed for bone health status using the
      Quantitative Ultrasound (QUS). Nutrient intake was assessed using a dietary
      history Questionnaire. Fasting serum lipid and blood pressure measurements were
      also taken. RESULTS: The majority of the subjects were overweight and obese (80%)
      based on BMI status. Calcaneal measurements using the QUS indicated that while
      57% or the subjects had normal bone mineral density, 37% were osteopenic and 6%
      osteoporotic. Calcium intake of the subjects was 505 +/- 263 mg /day, which is
      only 50% of the Malaysian Recommended Nutrient Intake for calcium (1000 mg/d).
      About 74% of the subjects were hypercholesterolemic and 58% were
      hypertriglyceridemic. Two-thirds reported that they were taking medication for
      hypertension, diabetes mellitus and heart disease. CONCLUSION: The results showed
      low health and nutritional status among post-menopausal women living in low-cost
      flats in Kuala Lumpur. They have low bone mass which may be due to their
      predominantly non-milk based diets which places them at high risk of hip
      fractures. Apart from milk, other food sources of calcium, including soya bean
      products such as 'tempeh' and healthy ways of cooking should be recommended to
      older people.

PMID- 24575665
TI  - Nutritional status and health-related quality of life of breast cancer patients
      on chemotherapy.
AB  - INTRODUCTION: Nutritional decline is typically accepted as a consequent of the
      course of treatment for cancer. This study aimed to (1) assess body weight status
      and dietary intake of breast cancer patients on chemotherapy and (2) to correlate
      Body Mass Index (BMI), energy and protein intake with health-related quality of
      life (HRQoL) profile. METHODS: A cross-sectional study was conducted in two
      government hospitals in the East coast of Peninsular Malaysia using convenience
      sampling. Women aged > or =18 years, who were diagnosed with breast cancer and
      receiving chemotherapy were invited to participate. The following aspects were
      evaluated: body weight status, usual dietary intake (diet history) and HRQoL
      (EORTC QLQ-C30). Descriptive statistics and non-parametric tests were employed
      (SPSS 16). RESULTS: Of the respondents, 41 were 49 +/- 9.6 years of age; 92.7%
      were Malay; 97.6% (response rate = 91%) were on moderately emetogenic
      chemotherapy. Over half of the patients were overweight or obese (mean BMI = 25.3
      +/- 1.1 kg/m2). The majority self-reported weight reduction (46.3%) but positive
      energy balance was detected with the current energy and protein intakes recorded
      at 1792.6 +/- 304.9 kcal/day (range= 1200-2500) and 74.5 g/day (IqR= 37.7)
      respectively. Dietary intakes were, however, not correlated with HRQoL, but
      greater BMI was associated with better emotional and cognitive functioning and
      less fatigue. CONCLUSION: Although most patients declared losing weight, obesity
      and excess dietary intake were noted. Additionally, body weight status has been
      shown to be important in HRQoL profile, underlining the necessity for effective
      nutritional assessments and support to the cancer population.

PMID- 24575666
TI  - Nutrition knowledge, attitude and practice of teachers in rehabilitation centres
      in northern Malaysia.
AB  - INTRODUCTION: Persons with disabilities (PWD) are susceptible to malnutrition.
      Caregivers or teachers in rehabilitation centres may not be adequately trained in
      nutrition management of PWD. The aims of this study were (i) to assess the
      nutrition knowledge, attitude and practice among teachers in community-based
      rehabilitation centres for PWD; and (ii) to evaluate changes in the nutrition
      knowledge and attitude of the teachers before and after exposure to a training
      workshop on nutrition management for PWD. METHODS: A cross-sectional survey was
      conducted using a guided self-administered Nutrition Knowledge, Attitude and
      Practice Questionnaire on Persons with Disabilities (KAP-nOKU), among a
      convenience sample of 210 teachers. Forty-five of them further participated in a
      nutrition training workshop and completed the post-test evaluation on knowledge
      and attitude of the same measures. RESULTS: At baseline, the teachers' average
      knowledge, attitude and practice scores were 13.80 +/- 3.73 for knowledge (below
      50th percentile); 51.49 +/- 4.08 for attitude (above 75th percentile); and 48.08
      +/- 3.61 for practice (between 50th and 75th percentile). There was significant
      positive correlations between knowledge and attitude (r=0.343, p<0.05), as well
      as between attitude and practice (r=0.147, p<0.05). After exposure to a 3-day
      nutrition workshop, significant improvements in the teachers' knowledge and
      attitude were observed, whereby teachers' knowledge score increased from 14.20 +/
      3.80 to 25.38 +/- 2.36 and from 51.16 +/- 3.97 to 55.20 +/- 4.41 for attitude
      (p<0.001). CONCLUSION: Nutrition intervention was associated with improvement in
      short term knowledge and attitude of the teachers. Sustainable interventional
      strategies are needed to enhance the nutrition knowledge and skills of teachers
      of PWD.

PMID- 24575667
TI  - Childhood obesity, self-esteem and health-related quality of life among urban
      primary schools children in Kuching, Sarawak, Malaysia.
AB  - INTRODUCTION: There is limited data on childhood obesity and its impact on
      children from diverse cultural backgrounds. This study is aimed at determining
      the association between obesity, self-esteem and health-related quality of life
      (HRQOL) among Malaysian urban primary school children of different ethnicity.
      METHODS: A cross-sectional study was conducted involving 311 children aged 11-13
      years from primary schools in Kuching, Sarawak. Self-esteem and health-related
      quality of life (HRQOL) were measured using the Lawrence Self-esteem
      Questionnaire (LAWSEQ) questionnaire and the Paediatric Quality of Life Inventory
      (PedsQL), respectively. Body weight and height were taken and body mass index for
      age calculated. RESULTS: The prevalence of overweight and obesity among the
      children were 18.2% and 15.2% respectively. Parent-proxy and child self-reported
      PedsQL scores were higher for normal weight children compared to thin and obese
      children, but lower than overweight children. At the subscale level, only parent
      proxy PedsQL scores in psychosocial health and emotional component were
      significantly different between overweight and obese children (p=0.019, p=0.02).
      The Self-esteem score was significantly correlated with parent and child PedsQL
      scores. Although obesity was associated with lower HRQOL among children, both
      parent and child PedsQL scores among the overweight group were higher than that
      for the normal weight group. Overweight and obesity did affect quality of life
      and self-esteem of children in this study, particularly in the areas of
      psychosocial and emotional health. CONCLUSION: Policy makers and programme
      managers should take into consideration the impact of obesity on children and
      parents in designing intervention programmes.

PMID- 24575668
TI  - Meal patterns of malaysian adults: findings from the Malaysian adults nutrition
      survey (MANS).
AB  - INTRODUCTION: Meal patterns have received little attention in nutrition studies.
      The aim of this study is to present the findings on general meal patterns of
      Malaysian adults. METHODS: The Malaysian Adults Nutrition Survey (MANS), carried
      out in 2002 and 2003, involved 6,928 adults selected by stratified random
      sampling from all households by zone in Peninsular Malaysia, Sabah and Sarawak.
      RESULTS: In general, the results showed that most respondents (74.16%) ate three
      meals per day; 89.20% of the respondents consumed breakfast, while 88.57%
      consumed lunch and 91.97% consumed dinner with no significant difference in terms
      of sex. In Peninsular Malaysia, the Northern Zone had the highest number of
      people consuming breakfast compared to other zones. Meanwhile, the population in
      Sarawak had the largest proportion of people consuming lunch and dinner, but the
      smallest proportion of people consuming breakfast. A significantly higher number
      of the rural population consumed breakfast and lunch than urbanites; however
      there was no significant difference in dinner consumption. Generally, breakfast
      consumption increased with age whereby significant difference existed between the
      18 to 19 years age group and the age group of 30 years and older. Lunch intake
      among the age groups showed no significant difference. In contrast, dinner
      consumption was significantly lower among the 18 to 19 years age group compared
      to all other age groups. Comparison among the ethnic groups showed that the
      Indian population had the lowest percentage of having breakfast and lunch while
      the Orang Asli had the lowest percentage of consuming dinner. However, the Orang
      Asli recorded the highest percentage for taking breakfast and lunch while the
      Chinese had the highest percentage of taking dinner. CONCLUSION: Considering that
      Malaysian adults consumed their conventional breakfast, lunch and dinner, these
      findings indicatethat Malaysians are maintaining their traditional meal patterns.

PMID- 24575669
TI  - Nutritional status, dietary intake patterns and nutrition knowledge of children
      aged 5-6 years attending kindergartens in the Klang Valley, Malaysia.
AB  - INTRODUCTION: Early childhood is a period during which many factors influence the
      development of lifelong eating habits. This study aimed to assess the nutritional
      status of young children and to determine factors related to eating habits.
      METHODS: A total of 992 children aged 5-6 years attending kindergartens that
      participated in the Bright Start Nutrition programme in the Klang Valley were
      included in the study. Anthropometric measurements were taken and body mass index
      (BMI) calculated. A questionnaire to assess the children's nutrition knowledge
      was administered through interviews, while their mothers self-administered
      another set of questionnaires regarding knowledge, attitude and practice on
      nutrition. RESULTS: The mean BMI was 15.7 +/- 2.7 kg/m2 in boys and 15.4 +/- 2.4
      kg/m2 in girls. Based on the WHO 2007 growth reference, the prevalence of
      overweight and obesity were 9.1% and 9.3%, respectively; while the prevalence of
      thinness and stunting were 5.8% and 3.9%, respectively. Most of the children
      consumed breakfast (86.4%), lunch (94.1%) and dinner (93.4%) daily. The majority
      liked fruits (95.1%), snacks (93.8%), Western fast food (93.3%) and milk (90.8%),
      while less than two-thirds (65.1%) liked vegetables. The mean nutrition knowledge
      scores for the children and mothers were 73.2 +/- 9.8% and 60.2 +/- 18.8%,
      respectively. Maternal nutrition knowledge was correlated positively with
      children's vegetable intake (r=0.111, p<0.05) and negatively with snack intake (r
      = -0.134, p<0.05). CONCLUSION: These results showed a higher prevalence of
      overweight and obesity than underweight and thinness among the urban young
      children studied. As mother's nutrition knowledge was found to exert a positive
      influence on children's eating habits, it is important to provide nutrition
      education to both mothers and children when conducting intervention programmes.

PMID- 24575671
TI  - Relationship between nutritional status, physical activity and quality of life
      among gastrointestinal cancer survivors.
AB  - INTRODUCTION: The objective of this study was to determine the relationship
      between nutritional status, physical activity and quality of life among
      gastrointestinal cancer survivors. METHODS: A cross-sectional study was conducted
      among gastrointestinal cancer survivors attending the oncology outpatient clinic
      in Hospital Selayang, Malaysia. RESULTS: A total of 70 gastrointestinal cancer
      survivors with a mean age of 52.54 +/- 14.59 years (95% CI: 47.48 - 57.60) were
      included in this study. Results showed that 40% of the patients were classified
      as having low physical activity. The mean Patient Generated Subjective Global
      Assessment (PGSGA) score was 10.27 +/- 7.36 (95% CI: 8.23-12.31) and nearly half
      the patients (48.6%) were identified as severely malnourished (Stage C). Mean
      Gastrointestinal Quality of Life Index (GQLFI) score was 103.57 +/- 23.85 (95%
      CI: 92.94-114.20), and about 24.3% of the patients were classified as having a
      low quality of life. Pearson's correlation test showed a highly significant
      negative relationship between nutritional status and quality of life (r = -0.661,
      p<0.001) indicating the better the nutritional status (low total mean score of
      PGSGA), the better the quality of life of the survivors (high total mean score of
      GQLFI). There was a significant negative relationship between physical activity
      level and nutritional status score (r = -0.309, p<0.01), indicating the higher
      the physical activity level of the patients (high MET-min/week), the better their
      nutritional status (low total mean score of PGSGA). CONCLUSION: This study shows
      a significant relationship between nutritional status, physical activity and
      quality of life among gastrointestinal cancer survivors. Those low in nutritional
      status have a low quality of life while survivors with higher nutritional status
      have a better quality of life.

PMID- 24575670
TI  - Food restrictions during pregnancy among Indigenous Temiar women in peninsular
      Malaysia.
AB  - INTRODUCTION: A qualitative comparative case study was conducted to compare and
      contrast food taboos and avoidance practices during pregnancy among Orang Asli or
      indigenous Temiar women in four distinct locations that represent different
      lifestyle experiences and cultural practices. METHODS: Through snowballing
      sampling, a total of 38 participants took part in five focus groups: one group
      each in Pos Simpor and Pos Tohoi in Kelantan state, one group in Batu 12, Gombak
      in Selangor state, and two groups in a regroupment scheme (RPSOA) in Kuala Betis,
      Kelantan. All the transcripts were coded, categorised and 'thematised' using the
      software package for handling qualitative data, NVivo 8. RESULTS: Variant food
      prohibitions were recorded among the Temiar women residing in different
      locations, which differ in food sources and ways of obtaining food. Consumption
      of seventeen types of food items was prohibited for a pregnant Temiar woman and
      her husband during the prenatal period. Fear of difficulties during labour and
      delivery, convulsions or sawan, harming the baby (such as foetal malformation),
      and twin pregnancy seemed to trigger many food proscriptions for the pregnant
      Temiar women, most of which have been passed on from generation to generation.
      CONCLUSION: The findings of this study confirm that beliefs about food
      restrictions are strong among those Temiar living a traditional lifestyle.
      However, those who have adopted a more modern lifestyle also preserve them to
      some extent.

PMID- 24575672
TI  - In vitro antioxidant activities of extract and oil from roselle (Hibiscus
      sabdariffa L.) seed against sunflower oil autoxidation.
AB  - INTRODUCTION: In order to overcome the stability problems of oils and fats,
      synthetic antioxidants such as butylated hydroxyanisole (BHA), butylated
      hydroxytoluene (BHT) and tert-butyl hydroquinone (TBHQ) have widespread use as
      food additives in many countries. Recent reports reveal that these compounds may
      be implicated in many health risks, including cancer and carcinogenesis. Hence,
      there is a move towards the use of natural antioxidants of plant origin to
      replace these synthetic antioxidants. METHODS: In this study, roselle seed oil
      (RSO) and extract (RSE) were mixed with sunflower oil, respectively to monitor
      degradation rate and investigate antioxidant activity during accelerated storage.
      RESULTS: The antioxidant activity was found to stabilise sunflower oil of various
      samples and in the order of RSE>RSO>tocopherol>sunflower oil. The total
      percentage increased after 5 days of storage period in free fatty acid (FFA),
      peroxide value (PV) and anisidine value (AV). Total oxidation value (TOx) of
      sunflower oil supplemented with 1500 ppm RSE was 33.3%, 47.7%, 14.5%, and 45.5%,
      respectively. While the total percentage increased under different analysis
      methods, sunflower oil supplemented with 5% RSO was 17.2%, 60.4%, 36.2% and 59.0%
      in the order of FFA, PV, AV and TOTOX. Both RSO and RSE were found to be more
      effective in stabilisation of sunflower oil compared to tocopherol. Total
      phenolic content of RSE was 46.40 +/- 1.51 mg GAE/100g of oil while RSO was 12.51
      +/- 0.15 mg GAE/ 100g of oil. CONCLUSION: The data indicates that roselle seed
      oil and seed extract are rich in phenolics and antioxidant activities and may be
      a potential source of natural antioxidants.

PMID- 24575673
TI  - Growth performance and nutrient composition of juvenile Nile tilapia (Oreochromis
      niloticus) fed Spirulina flakes, rice bran and mustard oil cake.
AB  - INTRODUCTION: Tilapia (Oreochromis niloticus) is an important cultured fish that
      is widely distributed in Bangladesh. This study was conducted to improve the
      growth performance and nutrient contents of the fish using five different types
      of feeds. METHODS: Tilapia fingerlings were fed two types of commercial fish
      feeds (Feed-1 and Feed-2), Spirulina flakes (Feed-3), Feed-2 mixed with Spirulina
      flakes (Feed-4) and manually mixed feed made from a mixture of mustard oil cake
      and rice bran (Feed-5). After 4 weeks of being fed with the diets, growth
      parameters and meat nutrient composition of the tilapia fingerlings were
      recorded. RESULTS: Significant growth in length and weight was observed in
      juvenile tilapia fish fed with commercial Feed-1 only, while growth performance
      varied significantly among fingerlings fed other types of feeds. Body tissue
      calcium (92.8 mg/100 g), iron (1.29 mg/100 g) was higher in fishes fed with dry
      Spirulina flakes (Feed 3), while the highest amount of zinc (2.09 mg/100 g) was
      recorded in fishes fed Feed-5. Protein (13.32%) content was highest in fish fed
      Feed-2 mixed with Spirulina flakes (Feed-4). CONCLUSION: Meat nutritional quality
      of tilapia can be improved by combining commercial feeds with Spirulina flakes,
      compared with feeding commercial feeds in isolation.

PMID- 24575674
TI  - Damning with faint praise: how homoeopaths talk about conventional medicine with
      their patients.
AB  - Homoeopathy is one of the most widely used forms of complementary medicine in the
      West. However, its methods and philosophical underpinnings are basically
      polarized in relation to those of conventional medicine. Many homoeopathic
      patients choose to continue using conventional medicine while they receive
      homoeopathy, but from a homoeopathic perspective, these treatments are often
      regarded as undesirable or even damaging. This article will utilize the
      principles of conversation analysis (CA) to explore points in homoeopathic
      consultations where practitioners address their patients' use of conventional
      medications. It will be suggested that approaches which display a degree of
      incorporation are preferred to those which imply categorical rejection. By not
      emphasizing the underlying tensions between conventional and homoeopathic
      paradigms, and displaying an adaptive and inclusive approach, homoeopathy
      essentially sets itself up as a parallel (i.e. equal) system, rather than one
      that is purely in opposition to the dominant medical model.

PMID- 24575676
TI  - Clinical handover as an interactive event: informational and interactional
      communication strategies in effective shift-change handovers.
AB  - Clinical handover -- the transfer between clinicians of responsibility and
      accountability for patients and their care (AMA 2006) -- is a pivotal and high
      risk communicative event in hospital practice. Studies focusing on critical
      incidents, mortality, risk and patient harm in hospitals have highlighted
      ineffective communication -- including incomplete and unstructured clinical
      handovers -- as a major contributing factor (NSW Health 2005; ACSQHC 2010). In
      Australia, as internationally, Health Departments and hospital management have
      responded by introducing standardised handover communication protocols. This
      paper problematises one such protocol - the ISBAR tool - and argues that the
      narrow understanding of communication on which such protocols are based may
      seriously constrain their ability to shape effective handovers. Based on analysis
      of audio-recorded shift-change clinical handovers between medical staff we argue
      that handover communication must be conceptualised as inherently interactive and
      that attempts to describe, model and teach handover practice must recognise both
      informational and interactive communication strategies. By comparing the
      communicative performance of participants in authentic handover events we
      identify communication strategies that are more and less likely to lead to an
      effective handover and demonstrate the importance of focusing close up on
      communication to improve the quality and safety of healthcare interactions.

PMID- 24575677
TI  - Negotiating behavioural change: therapists' proposal turns in Cognitive
      Behavioural Therapy.
AB  - Cognitive behavioural therapy (CBT) is an internationally recognised method for
      treating depression. However, many of the techniques involved in CBT are
      accomplished within the therapy interaction in diverse ways, and with varying
      consequences for the trajectory of therapy session. This paper uses conversation
      analysis to examine some standard ways in which therapists propose suggestions
      for behavioural change to clients attending CBT sessions for depression in
      Australia. Therapists' proposal turns displayed their subordinate epistemic
      authority over the matter at hand, and emphasised a high degree of optionality on
      behalf of the client in accepting their suggestions. This practice was routinely
      accomplished via three standard proposal turns: (1) hedged recommendations; (2)
      interrogatives; and (3) information-giving. These proposal turns will be examined
      in relation to the negotiation of behavioural change, and the implications for
      CBT interactions between therapist and client will be discussed.

PMID- 24575675
TI  - Preserving the child as a respondent: initiating patient-centered interviews in a
      US outpatient tertiary care pediatric pain clinic.
AB  - This article identifies some of the challenges of implementing patient
      centeredness in multiparty clinical visits. Specifically, it describes four
      interview practices with which clinicians address these challenges in a US
      outpatient tertiary care pediatric pain clinic. Using the qualitative method of
      conversation analysis, we analyze clinicians' child-directed (ages 10-18)
      interviewing during the initial stage of 51 intake visits. In particular, we
      analyze the challenges involved in open-ended questioning, a form of interviewing
      associated with patient-centeredness. Open-ended questioning presents
      participants with competing demands: although it gives children an opportunity to
      talk about their illness in their own terms, it also asks them to be responsible
      for a larger part of the communication work. Moreover, the presence of a parent
      as an alternative informant can lead to the loss of the child as an informant if
      clinicians fail to give the child, particularly younger ones, enough guidance in
      answering. We argue that a flexible range of interviewing practices may be a step
      towards offsetting children's and parents'past negative experiences with
      clinicians, improving patient outcomes and implementing child/patient
      centeredness.

PMID- 24575678
TI  - Role of Islamic religious and cultural beliefs regarding intellectual impairment
      and service use: a South Asian parental perspective.
AB  - Empirical research has shown that some South Asian families from Muslim
      backgrounds may use fewer additional support services for their severely impaired
      children compared to other non-Muslim families. Often this has been attributed to
      socioeconomic factors and stereotypical views such as "the family's faith
      prohibits the use of specific services". This paper focuses on clarifying what
      Islam purports to say about impairment and considers how cultural influences may
      inadvertently influence some South Asian parents' decisions to use services for
      their severely impaired children. This work aims to improve professional
      parent/patient communication by enhancing better understanding of Islam on
      impairment, and supporting non-Muslim professionals to appreciate the differences
      between Islamic religion and general South Asian cultural beliefs regarding
      disability. Fourteen parents from ten Pakistani and Bangladeshi families took
      part in semi-structured open-ended interviews. Grounded theory was used to
      analyse the data. The emerging theory suggested most first generation Muslim
      families from rural villages were unable to distinguish between Islamic religious
      and cultural beliefs on impairment, and risked missing out on essential services
      due to poor professional-parent/patient communication.

PMID- 24575679
TI  - "Disciplining witnesses" in the teaching of physiotherapy: some insights into the
      practical accomplishment of a science-based healthcare profession.
AB  - Physiotherapy in the UK defines itself as a "science-based healthcare
      profession". Physiotherapy students must undertake at least one thousand hours of
      learning in live practice settings. Adopting an analytic stance shaped by
      interaction analysis and workplace studies, and drawing on observational data of
      placement settings, this paper examines some features of the means by which
      physiotherapy education is practically accomplished. The paper introduces and
      utilises a novel notational system for capturing movement and touch in
      ethnographic fieldwork notes. Our analysis draws upon ideas from Lynch and
      Macbeth's (1998) study of elementary school science classes. We focus in
      particular on their notion of "disciplining witnesses" to illustrate how science
      is enacted -- and plays a privileged role -- within the everyday accomplishment
      of practice-based physiotherapy education. We show how patients are disciplined
      to provide information on cue and to act as props for therapeutic demonstrations,
      while students are disciplined to co-produce standard interpretations of the
      science of physiotherapy. We conclude the paper with a brief discussion of the
      ways in which these insights offer a new perspective for physiotherapy
      practitioners and educators in understanding the nature of interactions entailed
      in their professional practice, and the role of patients within those
      interactions.

PMID- 24575680
TI  - Attempting to standardise ethical review within the complexity of health-related
      research.
AB  - Researchers in medicine, allied disciplines and elsewhere submit research
      proposals to an ethical review board before research commences. This paper argues
      that the effectiveness of review relies on reviewers using discernment and
      judgement when applying standardised review criteria so that they accommodate the
      full range of research projects. With reference to ethics literature, the paper
      identifies five imperatives in the development of review guidelines and
      processes. It examines case composition and analysis, and explores interactions
      between professional developers, researchers and reviewers to illustrate problems
      in the review process. It refers to the ethical review system in New Zealand and
      the report to parliament: Inquiry into Improving New Zealand's Environment to
      Support Innovation through Clinical Trials (Health Committee 2011). Seeking to
      gain for New Zealand a competitive edge in clinical research, this report made 19
      recommendations to improve the climate for clinical trials, ethical review
      included, in this country. The connection between these two case studies is the
      common endeavour to standardise the ethical review exercise, review systems and
      review processes. Cases with commentary are a recommended addition to guidelines
      documents to present research within its context and to demonstrate the
      complexity that a standardised ethical review does not always address.

PMID- 24575681
TI  - Creating a culture of 'we' investing in physician leaders.

PMID- 24575682
TI  - Essential strategies for hospital-physician relations.

PMID- 24575683
TI  - The ethics of access to care and care disparities.

PMID- 24575685
TI  - Are you taking time for your career development?

PMID- 24575684
TI  - Women in leadership. Despite progress, inequalities still exist.

PMID- 24575686
TI  - Why hold people accountable?

PMID- 24575687
TI  - Moral management as a leadership priority. Treating employees well and managing
      ethically is a business imperative.

PMID- 24575688
TI  - Engaging leaders in the patient experience. Six essential steps help leaders make
      patient engagement a priority.

PMID- 24575689
TI  - Minutes are muscle: a cardiac lifesaver.

PMID- 24575691
TI  - Your future gets brighter with emotional intelligence. A high EQ is essential to
      keeping your career on an upward path.

PMID- 24575690
TI  - The employer mandate delay. An opportunity for provider-based health plans.

PMID- 24575692
TI  - Engaging boards in the transition from volume to value. Addressing the "why"
      before presenting the "how".

PMID- 24575694
TI  - Hospital-physician compacts: a journey worth taking.

PMID- 24575693
TI  - A focus on 'always events'. Strategy ensures patient-centered care and a better
      patient experience.

PMID- 24575695
TI  - Teams--pride and passion.

PMID- 24575696
TI  - "Second victim" casualties and how physician leaders can help.
AB  - Although medical mistakes hurt patients first, they often leave doctors feeling
      upset and depressed, as well. Take a look at some ways health care organizations
      can help the physician second victims.

PMID- 24575697
TI  - How to be the best doctor.

PMID- 24575698
TI  - Addressing satisfaction gaps around cultural fit.

PMID- 24575699
TI  - Navigating conflict while constructing your patient-centered medical home.

PMID- 24575700
TI  - One hospitals journey with the influenza vaccine.

PMID- 24575701
TI  - Revisiting the triple aim--are we any closer to integrated health care?
AB  - Are we, as a nation, any closer to integrated health care? Have the preconditions
      for the pursuit of the Triple Aim been achieved? Can the U.S. health care
      delivery system pass the "Triple aim test?".

PMID- 24575702
TI  - Medicare: 'We want our money back'!

PMID- 24575704
TI  - Financial transparency and physicians: the physician leader's guide to sharing
      numbers.
AB  - Review critical factors such as length of stay, case mix, financial statements,
      ratios and days cash on hand that physicians need to understand to adequately
      manage hospital patients and engage in the success of the organization.

PMID- 24575703
TI  - The New Jersey gainsharing experience.

PMID- 24575705
TI  - A glimpse of health care reform's next chapter.

PMID- 24575706
TI  - The Affordable Care Act and electronic health care records: can technology help
      reduce the cost of health care?

PMID- 24575707
TI  - Meet Paul Weisman, MD--consultant, coach, entrepreneur.

PMID- 24575708
TI  - How to get the most out of your coaching.

PMID- 24575709
TI  - How physician leaders can use social media to crowdsource.

PMID- 24575710
TI  - Systematic investigation of the physicochemical factors that contribute to the
      toxicity of ZnO nanoparticles.
AB  - ZnO nanoparticles (NPs) are prone to dissolution, and uncertainty remains whether
      biological/cellular responses to ZnO NPs are solely due to the release of Zn(2+)
      or whether the NPs themselves have additional toxic effects. We address this by
      establishing ZnO NP solubility in dispersion media (Dulbecco's modified Eagle's
      medium, DMEM) held under conditions identical to those employed for cell culture
      (37  degrees C, 5% CO2, and pH 7.68) and by systematic comparison of cell-NP
      interaction for three different ZnO NP preparations. For NPs at concentrations up
      to 5.5 MUg ZnO/mL, dissolution is complete (with the majority of the soluble zinc
      complexed to dissolved ligands in the medium), taking ca. 1 h for uncoated and
      ca. 6 h for polymer coated ones. Above 5.5 MUg/mL, the results are consistent
      with the formation of zinc carbonate, keeping the solubilized zinc fixed to 67
      MUM of which only 0.45 MUM is as free Zn(2+), i.e., not complexed to dissolved
      ligands. At these relatively high concentrations, NPs with an aliphatic polyether
      coating show slower dissolution (i.e., slower free Zn(2+) release) and
      reprecipitation kinetics compared to those of uncoated NPs, requiring more than
      48 h to reach thermodynamic equilibrium. Cytotoxicity (MTT) and DNA damage
      (Comet) assay dose-response curves for three epithelial cell lines suggest that
      dissolution and reprecipitation dominate for uncoated ZnO NPs. Transmission
      electron microscopy combined with the monitoring of intracellular Zn(2+)
      concentrations and ZnO-NP interactions with model lipid membranes indicate that
      an aliphatic polyether coat on ZnO NPs increases cellular uptake, enhancing
      toxicity by enabling intracellular dissolution and release of Zn(2+). Similarly,
      we demonstrate that needle-like NP morphologies enhance toxicity by apparently
      frustrating cellular uptake. To limit toxicity, ZnO NPs with nonacicular
      morphologies and coatings that only weakly interact with cellular membranes are
      recommended.

PMID- 24575712
TI  - Behavior and determination of titanium dioxide nanoparticles in nitric acid and
      river water by ICP spectrometry.
AB  - ICP spectrometry (ICPMS, ICPOES) are classical techniques for the determination
      of solubilized or suspended elements. Unfortunately, their relevance for
      nanoparticles at low concentration (below 10 ppm) is rarely called into question,
      even if literature reports are not always coherent. This work is a systematic
      study based on the measurement of TiO2 nanoparticle suspensions, as a model of
      quasi-insoluble material, by plasma spectrometry. It studies both sample
      treatment and measurement in the 10 ppb to 30 ppm concentration range. Realized
      on a set of four engineered nanoparticles suspensions at low concentration, it
      shows the existence of three different regimes of stability that affect
      concentration measurement. Above a C(S) stability concentration value,
      suspensions are stable in time; below a low-concentration C(E) value, the signal
      loss is at a maximum, and a final partition is reached between the container
      walls and the suspension. Between these two regimes, the suspension aging varies
      with concentration. C(E) and C(S) depend on nanoparticle characteristics and the
      suspension medium, whereas the evolution kinetic is volume-dependent. Because
      TiO2 nanoparticles are present in the environment at concentrationd below C(S),
      it is then necessary to find a way to rehomogenize the suspension between
      sampling and analyzing. Soft sonication, minimizing the sample temperature, and
      trapping of free radicals is proposed and evaluated. Homogenization is traced by
      the addition of an internal standard before storage. The procedure is applied to
      a real sample, Seine River water. The amount of total titanium found, 48.7 ppb,
      is in good agreement with the result of the reference method. 

PMID- 24575711
TI  - Cytokines in healthy temporomandibular joint synovial fluid.
AB  - Analysis of temporomandibular joint (TMJ) synovial fluid may elucidate the
      aetiology of temporomandibular disorders and arthritic conditions, as well as the
      inflammatory mechanisms involved. Knowledge about healthy synovial fluid is
      necessary to understand TMJ pathologies. We aimed to quantify the proinflammatory
      cytokines interleukin (IL)-1beta, IL-2, IL-6 and tumour necrosis factor (TNF),
      and the anti-inflammatory cytokines IL-10 and interferon (IFN)-gamma in healthy
      TMJ synovial fluid to serve as reference values for future studies on TMJ
      pathologies. Twenty healthy, young adult volunteers without temporomandibular
      dysfunction were included. Bilateral synovial fluid samples were obtained using
      the push-pull technique with hydroxocobalamin described by Alstergren in 1999.
      Cytokines were quantified with Luminex multiplex assays and compared using
      nonparametric statistical analysis. No serious adverse effects were reported. Of
      40 possible samples, 14 fulfilled the strict sampling criteria and were included
      in the analysis. Cytokine values (reported as medians with interquartile ranges)
      were as follows: TNF, 23 (13-37) pg mL(-1) ; IL-2, 1.8 (0-22) pg mL(-1) ; and INF
      gamma, 10 (0-47) pg mL(-1) . IL-1beta, IL-6 and IL-10 were almost undetectable.
      In addition, TNF and INF-gamma cytokine levels correlated. We demonstrated that
      TNF was consistently detected and IFN-gamma and IL-2 sporadically detected in the
      TMJ synovial fluid of healthy individuals using the hydroxocobalamin method and a
      multiplex assay. The cytokines IL-10, IL-1beta and IL-6 were barely detectable in
      this sample of healthy TMJs. 

PMID- 24575713
TI  - Seroprevalence survey of Q fever among sheep in northwestern Iran.
AB  - Q fever is a disease caused by Coxiella burnetii, which infects both humans and
      certain animals, and is considered a public health problem. There is a lack of
      information on its status in most parts of Iran, including the northwestern area,
      which is one of the main centers of animal husbandry in Iran. This study was
      carried out to evaluate the seroprevalence of Q fever among sheep in the province
      of Ardabil in northwestern Iran. In all, 253 sheep samples were collected from
      different regions (north, central, and south) of Ardabil Province. Sera were
      tested by a CHEKIT Q fever enzyme-linked immunosorbent assay (ELISA) kit for
      detection of C. burnetii immunoglobulin G (IgG). A total of 33.6% of sheep sera
      and 87.50% of herds were positive for C. burnetii IgG. There was a significant
      difference between the regions studied (p<0.001) and the highest and the lowest
      rate of seroprevalence were seen in the south (58.6%) and central (23.3%)
      regions, respectively. Most of the seropositive cases were observed in 3- to 4
      year-old the sheep (46.1%). There was no relationship between gender and the
      seroprevalence rate. Although this study was the first survey of Q fever in
      northwestern Iran, the high seroprevalence rate indicates that further attention
      should be paid to this disease in this region of the country.

PMID- 24575714
TI  - Racial and ethnic variation in pain following inpatient palliative care
      consultations.
AB  - Studies have documented high levels of pain in hospitalized individuals at the
      end of life, with minorities reporting higher levels of pain than whites. In
      response, inpatient palliative care (IPC) teams have grown rapidly to improve
      care of seriously ill individuals. Although research indicates that IPC teams
      effectively reduce and maintain control of pain, racial and ethnic differences in
      pain following IPC consultation remain unclear. This study investigated racial
      and ethnic pain differences after an IPC intervention in 385 seriously ill white,
      black, and Latino individuals aged 65 and older. Using the 11-point Numeric
      Rating Scale for pain, individuals were asked to rate their pain intensity at
      four points during hospitalization (before IPC consultation, 2 and 24 hours after
      the consultation, and at hospital discharge). Results indicate that whites
      (F1.657, 173.998 = 16.528, P < .001), blacks (F1.800, 95.410 = 7.103, P = .002),
      and Latinos (F1.388, 73.584 = 10.902, P < .001) all experienced significant
      reductions in pain after the intervention. Adjusted multivariate models testing
      between-group racial and ethnic differences revealed that Latinos were 62% more
      likely than whites to report experiencing pain at hospital discharge (relative
      risk = 0.38, 95% confidence interval = 0.15-0.97). Regardless of race or
      ethnicity, IPC effectively reduces and controls pain after consultation. Despite
      pain decreases, Latinos remain more likely than whites to report pain at follow
      up. Further research is needed to determine the mechanisms in operation and to
      better understand and address the needs of this population.

PMID- 24575715
TI  - Polymer-supported stereoselective synthesis of tetrahydrobenzopyrazino
      thiadiazinone dioxides via N-sulfonyl iminiums.
AB  - The stereoselective synthesis of 1,2,11,11a-tetrahydrobenzo[e]pyrazino[1,2
      b][1,2,4]thiadiazin-3(4H)-one 6,6-dioxides on a solid support via tandem N
      sulfonyl iminium ion cyclization, followed by nucleophilic addition is reported.
      The synthesis proceeded with full control of stereoselectivity at the newly
      formed asymmetric carbon, under mild conditions, and using commercially available
      building blocks. The synthetic route provided high-purity crude products. 

PMID- 24575716
TI  - Recovery of golfing ability in someone with an incomplete spinal cord injury: a
      case report.
AB  - PURPOSE: The purpose of this case report was to describe the elements needed to
      play golf, detail a rehabilitation program designed to teach someone with an
      incomplete spinal cord injury (SCI) to play golf and to document outcomes of such
      a program. METHODS: The participant was a 58-year-old male who sustained an
      incomplete C3-C6 SCI. The program was divided into three phases. Phase one (nine
      sessions) consisted of balance, strengthening and flexibility activities to
      prepare him to play golf. During phase two (12 sessions), he practiced his golf
      swing in a clinical setting and in phase three (seven sessions) focused on task
      oriented training at a golf course. The ability to play golf, putting accuracy,
      driving distance, quality of swing, balance, physical functioning, walking
      capacity, muscle strength, endurance and quality of life were measured before and
      after the intervention. RESULTS: The participant was able to complete 9-holes of
      golf with assistance and demonstrated greater ability to drive the ball with
      better quality of swing. Improvements were observed in balance, physical
      functioning, walking capacity, endurance and quality of life but not in overall
      strength or putting accuracy. CONCLUSIONS: This individual was able to return to
      golf following an intense rehabilitation program even though he required an
      assistive device to walk. Implications for Rehabilitation Individuals with spinal
      cord injury often have impairments which make participation in leisure activities
      more difficult. Participation in leisure activities has been associated with
      better subjective well being and quality of life. Rehabilitation therapists
      should consider creating leisure goals with their patients.

PMID- 24575717
TI  - The therapeutic role of motor imagery on the functional rehabilitation of a stage
      II shoulder impingement syndrome.
AB  - PURPOSE: Motor imagery (MI) has been used as a complementary therapeutic tool for
      motor recovery after central nervous system disease and peripheral injuries.
      However, it has never been used as a preventive tool. We investigated the use of
      MI in the rehabilitation of stage II shoulder impingement syndrome. For the first
      time, MI is used before surgery. METHOD: Sixteen participants were randomly
      assigned to either a MI or control group. Shoulder functional assessment
      (Constant score), range of motion and pain were measured before and after
      intervention. RESULTS: Higher Constant score was observed in the MI than in the
      control group (p=0.04). Participants in the MI group further displayed greater
      movement amplitude (extension (p<0.001); flexion (p=0.025); lateral rotation
      (p<0.001). Finally, the MI group showed greater pain decrease (p=0.01).
      CONCLUSION: MI intervention seems to alleviate pain and enhance mobility, this is
      probably due to changes in muscle control and consequently in joint amplitude. MI
      might contribute to postpone or even protect from passing to stage III that may
      require surgery. Implications for Rehabilitation Adding motor imagery training to
      classical physical therapy in a stage II impingement syndrome: Helps in
      alleviating pain Enhances shoulder mobility Motor imagery is a valuable technique
      that can be used as a preventive tool before the stage III of the impingement
      syndrome.

PMID- 24575720
TI  - Association between structural and functional connectivity in the verb generation
      network.
AB  - The decade-long endeavor to link brain structure with brain function has met with
      varying degrees of success. Recent advances in imaging techniques allow a fresh
      look at the issue, however. In the current investigation, functional magnetic
      resonance imaging and diffusion tensor imaging (DTI) were employed to directly
      investigate the link between functional connectivity during a verb generation
      task and the underlying structural substrate. Nineteen participants performed a
      verb generation task during functional scanning and also underwent DTI. A
      psychophysiological interaction analysis was used to map the functional networks
      recruited during the task and as an index of functional connectivity. The degree
      to which this correlated with diffusion measures was used to explore the
      existence of anatomofunctional relationships within the identified connections. A
      significant correlation was seen for the middle frontal (MFG) to precentral gyrus
      pathway, where a pattern of low fractional anisotropy and high perpendicular
      diffusion was associated with low functional connectivity. A second pathway
      between the MFG and inferior temporal gyrus did not show a significant
      correlation, which may be attributed to two independent factors that might be
      influencing the structural properties of this pathway. The variation in structure
      function relationships within this network may relate to each pathways
      involvement in different cognitive functions.

PMID- 24575718
TI  - ICF-based functional components and contextual factors as correlates of perceived
      quality of life for youth with chronic conditions.
AB  - PURPOSE: To explore International Classification of Functioning, Disability and
      Health (ICF)-based functional components and contextual factors associated with
      perceived quality of life (QOL) for youth with chronic conditions from the
      perspective of youth and parents. METHOD: Baseline data were obtained from a
      longitudinal study examining predictors of changes in perceived QOL for youth
      with chronic conditions. 439 youth aged 11-17 (and one of their parents)
      completed a questionnaire. Standardized tools were used to measure youth
      functioning, contextual factors and perceived QOL. Multivariate linear regression
      analyses, controlling for socio-demographic and health information, were
      conducted to explore correlations among youth functioning/contextual factors and
      youth and parent perceptions of youth QOL. RESULTS: Significant (p <= 0.05)
      negative correlates with both youth and parent perceptions of youth QOL included
      pain/other physical symptoms and emotional symptoms. Significant factors
      positively correlated with youth and parent perceptions of youth QOL included
      school productivity and spirituality. Other significant positive correlates of
      youth perspectives were family social support and school belongingness/safety.
      Family functioning was positively correlated, and youth social anxiety and
      environmental barriers were negatively correlated, with parent perceptions of
      youth QOL. CONCLUSIONS: This study provides preliminary evidence of factors upon
      which services aimed at improving perceived QOL of youth with chronic conditions
      could be based. IMPLICATIONS FOR REHABILITATION: This study supports the utility
      of clinicians assessing the QOL of youth with chronic conditions in terms of
      youths' and their families' perspectives. This is the first study to identify key
      factors that impact perceived QOL at one point in time across a group of youth
      with chronic conditions, offering clinicians a main starting-point for
      considering youths' strengths and needs and the supportiveness of the
      environment. Findings suggest youth and families would benefit from the
      availability of services that encompass the full scope of the ICF.

PMID- 24575721
TI  - Metabolic adaptation to sugar/O2 deficiency for anaerobic germination and
      seedling growth in rice.
AB  - Rice is characterized by a broad range of metabolic and morphological adaptations
      to flooding, such as germination and mobilization of stored nutrients under
      submergence until seedlings reach the water surface to carry out photosynthesis,
      and sustainable growth of mature plants for long durations under partial
      submergence. The underlying mechanisms of the molecular basis of adaptation to
      anaerobic germination and seedling growth in rice are being uncovered. Induction
      of an ensemble of hydrolases to mobilize endosperm nutrient reserves is one of
      the key factors for successful germination and coleoptile elongation in rice
      under submergence. To compensate for reduced efficiency of Tricarboxylic Acid
      cycle and oxidative respiration in mitochondria under O2 deficient conditions,
      alpha-amylases play a central role in the hydrolysis of starch to provide sugar
      substrates for glycolysis and alcohol fermentation for generating ATP. We review
      the progress on the molecular mechanism regulating alpha-amylase expression that
      involves the integration of signals generated by the hormone gibberellin (GA),
      sugar starvation and O2 deprivation that results in germination and sustainable
      seedling growth in rice under anaerobic conditions. Comparisons are also made
      between dicots and monocots for the molecular mechanism of induction of genes
      involved in alcohol fermentation and sugar/O2 deficiency sensing system. 

PMID- 24575723
TI  - Imposing a pause between the eccentric and concentric phases increases the
      reliability of isoinertial strength assessments.
AB  - This study analysed the effect of imposing a pause between the eccentric and
      concentric phases on the biological within-subject variation of velocity- and
      power-load isoinertial assessments. Seventeen resistance-trained athletes
      undertook a progressive loading test in the bench press (BP) and squat (SQ)
      exercises. Two trials at each load up to the one-repetition maximum (1RM) were
      performed using 2 techniques executed in random order: with (stop) and without
      (standard) a 2-s pause between the eccentric and concentric phases of each
      repetition. The stop technique resulted in a significantly lower coefficient of
      variation for the whole load-velocity relationship compared to the standard one,
      in both BP (2.9% vs. 4.1%; P = 0.02) and SQ (2.9% vs. 3.9%; P = 0.01). Test
      retest intraclass correlation coefficients (ICCs) were r = 0.61-0.98 for the
      standard and r = 0.76-0.98 for the stop technique. Bland-Altman analysis showed
      that the error associated with the standard technique was 37.9% (BP) and 57.5%
      higher (SQ) than that associated with the stop technique. The biological within
      subject variation is significantly reduced when a pause is imposed between the
      eccentric and concentric phases. Other relevant variables associated to the load
      velocity and load-power relationships such as the contribution of the propulsive
      phase and the load that maximises power output remained basically unchanged.

PMID- 24575722
TI  - Analysis of glycan variation on glycoproteins from serum by the reverse lectin
      based ELISA assay.
AB  - Altered glycosylation in glycoproteins is associated with carcinogenesis, and
      certain glycan structures and glycoproteins are well-known markers for tumor
      progression. To identify potential diagnostic candidate markers, we have
      developed a novel method for analysis of glycosylation changes of glycoproteins
      from crude serum samples using lectin-based glycoprotein capture followed by
      detection with biotin/HRP-conjugated antibodies. The amount of lectin coated on
      the microplate well was optimized to achieve low background and improved S/N
      compared with current lectin ELISA methods. In the presence of competing sugars
      of lectin AAL or with sialic acid removed from the glycoproteins, we confirmed
      that this method specifically detects glycosylation changes of proteins rather
      than protein abundance variation. Using our reverse lectin-based ELISA assay,
      increased fucosylated haptoglobin was observed in sera of patients with ovarian
      cancer, while the protein level of haptoglobin remained the same between cancers
      and noncases. The combination of fucosylated haptoglobin and CA125 (AUC = 0.88)
      showed improved performance for distinguishing stage-III ovarian cancer from
      noncases compared with CA125 alone (AUC = 0.86). In differentiating early-stage
      ovarian cancer from noncases, fucosylated haptoglobin showed comparable
      performance to CA125. The combination of CA125 and fucosylated haptoglobin
      resulted in an AUC of 0.855, which outperforms CA125 to distinguish early-stage
      cancer from noncases. Our study provides an alternative method to quantify
      glycosylation changes of proteins from serum samples, which will be essential for
      biomarker discovery and validation studies. 

PMID- 24575725
TI  - Interventions for alleviating loneliness among older persons: a critical review.
AB  - OBJECTIVES: Loneliness is common among older persons and has been associated with
      health and mental health risks. This systematic review examines the utility of
      loneliness interventions among older persons. DATA SOURCE: Thirty-four
      intervention studies were used. STUDY INCLUSION CRITERIA: The study was conducted
      between 1996 and 2011, included a sample of older adults, implemented an
      intervention affecting loneliness or identified a situation that directly
      affected loneliness, included in its outcome measures the effects of the
      intervention or situation on loneliness levels or on loneliness-related measures
      (e.g., social interaction), and included in its analysis pretest-posttest
      comparisons. DATA EXTRACTION: Studies were accessed using the databases PsycINFO,
      MEDLINE, ScienceDirect, AgeLine, PsycBOOKS, and Google Scholar for the years 1996
      2011. DATA SYNTHESIS: Interventions were classified based on population, format,
      and content and were evaluated for quality of design and efficacy. RESULTS:
      Twelve studies were effective in reducing loneliness according to the review
      criteria, and 15 were evaluated as potentially effective. The findings suggest
      that it is possible to reduce loneliness by using educational interventions
      focused on social networks maintenance and enhancement. CONCLUSIONS: Multiple
      approaches show promise, although flawed design often prevents proper evaluation
      of efficacy. The value of specific therapy techniques in reducing loneliness is
      highlighted and warrants a wider investigation. Studies of special populations,
      such as the cognitively impaired, are also needed.

PMID- 24575724
TI  - Evidence to support including lifestyle light-intensity recommendations in
      physical activity guidelines for older adults.
AB  - PURPOSE: The purpose of this study was to examine the association of objectively
      measured lifestyle light-intensity physical activity (LLPA) and moderate-to
      vigorous physical activity (MVPA) with various biological markers and chronic
      diseases among a nationally representative sample of U.S. older adults (65+
      years). DESIGN: A cross-sectional design was used for this study. SETTING: Data
      were obtained from the National Health and Nutrition Examination Survey (NHANES)
      2003-2006. SUBJECTS: Subjects were 1,496 older U.S. adults. MEASURES:
      Participants wore an accelerometer for at least 4 days and completed
      questionnaires to assess sociodemographics and chronic disease information. Blood
      samples were taken to assess biological markers. ANALYSIS: Adjusted Wald tests
      and Poisson regression were used to examine the association of LLPA and MVPA with
      biological markers and chronic disease. RESULTS: Older adults engaging in >=300
      min/wk of LLPA had lower observed values for body mass index, waist
      circumference, C-reactive protein, and insulin resistance compared to those
      engaging in <300 min/wk of LLPA. Additionally, those engaging in <300 min/wk of
      LLPA had a rate 1.18 times greater for having chronic disease compared to those
      engaging in >=300 min/wk of LLPA. CONCLUSION: In this national sample of older
      U.S. adults, participation in at least 300 min/wk of LLPA was associated with
      more favorable health outcomes. Future experimental studies are warranted to
      confirm these findings.

PMID- 24575726
TI  - Lessons learned from community-based approaches to sodium reduction.
AB  - PURPOSE: This article describes lessons from a Centers for Disease Control and
      Prevention initiative encompassing sodium reduction interventions in six
      communities. DESIGN: A multiple case study design was used. SETTING: This
      evaluation examined data from programs implemented in six communities located in
      New York (Broome County, Schenectady County, and New York City); California (Los
      Angeles County and Shasta County); and Kansas (Shawnee County). SUBJECTS:
      Participants (n = 80) included program staff, program directors, state-level
      staff, and partners. MEASURES: Measures for this evaluation included challenges,
      facilitators, and lessons learned from implementing sodium reduction strategies.
      ANALYSIS: The project team conducted a document review of program materials and
      semistructured interviews 12 to 14 months after implementation. The team coded
      and analyzed data deductively and inductively. RESULTS: Five lessons for
      implementing community-based sodium reduction approaches emerged: (1) build
      relationships with partners to understand their concerns, (2) involve individuals
      knowledgeable about specific venues early, (3) incorporate sodium reduction
      efforts and messaging into broader nutrition efforts, (4) design the program to
      reduce sodium gradually to take into account consumer preferences and taste
      transitions, and (5) identify ways to address the cost of lower-sodium products.
      CONCLUSION: The experiences of the six communities may assist practitioners in
      planning community-based sodium reduction interventions. Addressing sodium
      reduction using a community-based approach can foster meaningful change in
      dietary sodium consumption.

PMID- 24575727
TI  - Menu labels displaying the kilocalorie content or the exercise equivalent:
      effects on energy ordered and consumed in young adults.
AB  - PURPOSE: Determine the effect of menu labels displaying the energy content of
      food items or the exercise equivalent on energy ordered and consumed at lunch and
      energy intake for the remainder of the day in young adults. DESIGN: Subjects were
      randomized to a menu with no labels (no-labels), menu with kilocalorie labels
      displaying the energy content of the food items (kcal-labels), or menu with
      exercise labels displaying the minutes of brisk walking needed to burn the food
      energy (exercise-labels). SETTING: The study was conducted in one dining area
      located in a metabolic kitchen at the Texas Christian University and another
      located in a residence occupied by graduate students. SUBJECTS: Of the 300
      subjects, 55.7% were female, 77.3% were college students, 88% were white, and 88%
      were non-Hispanic. Mean body mass index and age were 24.2 +/- 4.5 kg/m(2) and
      21.9 +/- 2.3 years, respectively. INTERVENTION: All menus contained the same
      food/beverage choices. Subjects ordered and consumed foods/beverages for lunch
      from the menu to which they were assigned. Subjects were blinded to study
      purpose. MEASURES: Energy ordered and consumed at lunch were assessed from the
      weight of the food ordered and consumed, respectively, and the energy content of
      the same foods available on the restaurant Web site. Postlunch energy intake was
      assessed by food recall. ANALYSIS: Analysis of covariance, adjusted for premeal
      hunger levels and gender, determined the effect of menu type on energy ordered
      and consumed and postlunch energy intake. RESULTS: Significant menu effect was
      observed for energy ordered (p = .008) and consumed (p = .04) at lunch. The
      exercise-labels group ordered significantly (p = .002) less energy (adjusted mean
      [confidence intervals]: 763 [703, 824] kcal) at lunch, compared to the no-labels
      group (902 [840, 963] kcal) but not compared to the kcal-labels group (827 [766,
      888] kcal). The exercise-labels group also consumed significantly (p = .01) less
      energy (673 [620, 725] kcal) at lunch, compared to the no-labels group (770 (717,
      823) kcal) but not compared to the kcal-labels group (722 [669, 776] kcal).
      Energy ordered and consumed were not different between kcal-labels and no-labels
      groups. There was no difference in postlunch energy intake by menu type.
      CONCLUSION: The menu with exercise-labels resulted in less energy ordered and
      consumed and this did not lead to greater energy consumption post lunch, compared
      to the menu with no-labels in young adults largely made up of normal-weight, non
      Hispanic white college students.

PMID- 24575729
TI  - S-aroylthiooximes: a facile route to hydrogen sulfide releasing compounds with
      structure-dependent release kinetics.
AB  - We report the facile preparation of a family of S-aroylthiooxime (SATO) H2S
      donors, which are synthesized via a click reaction analogous to oxime formation
      between S-aroylthiohydroxylamines (SATHAs) and aldehydes or ketones. Analysis of
      cysteine-triggered H2S release revealed structure-dependent release kinetics with
      half-lives from 8-82 min by substitution of the SATHA ring. The pseudo-first
      order rate constants of substituted SATOs fit standard linear free energy
      relationships (rho = 1.05), demonstrating a significant sensitivity to electronic
      effects. 

PMID- 24575728
TI  - A mixed-methods study of young adults' receptivity to using Facebook for smoking
      cessation: if you build it, will they come?
AB  - PURPOSE: To determine whether young adults are interested in a Facebook
      intervention for smoking cessation and to inform the design of such an
      intervention. DESIGN: Mixed-methods. SETTING: Participants throughout the United
      States were recruited through Facebook. PARTICIPANTS: Young adults aged 18 to 25
      years who had smoked at least once in the past month. METHOD: Participants (N =
      570) completed an online survey of tobacco and social media use. A subset of 30
      survey completers, stratified by motivation to quit smoking, agreed to
      participate in a structured interview over online chat. Themes were identified by
      using grounded theory. RESULTS: Approximately a third of the full sample (31%)
      reported they would want to get help to quit smoking by using Facebook. Interest
      in using Facebook to quit was greater among those who were more motivated to quit
      (chi(2) = 75.2, p < .001), had made a quit attempt in the past year (chi(2) =
      16.0, p < .001), and had previously used the Internet for assistance with a quit
      attempt (chi(2) = 6.2, p = .013). In qualitative interviews, social support and
      convenience were identified as strengths of a Facebook intervention, while
      privacy was the main issue of concern. CONCLUSION: Nearly one in three young
      adult smokers on Facebook expressed interest in using Facebook for quitting
      smoking. Social media approaches that respect privacy and tailor to readiness to
      quit are likely to maximize participation.

PMID- 24575730
TI  - Views of obstetric practitioners and hospital pharmacists on therapeutic goods
      administration approved product information for pregnancy and lactation.
AB  - This study investigated views and experiences of over 40 health professionals
      regarding pregnancy and lactation advice in Australian Product Information (PI).
      Quality up-to-date information is required when prescribing medication to this
      demographic. It was found that reliance on PI can result in negative
      ramifications. These interviews amplify earlier, somewhat limited evidence that
      PI recommendations are likely overconservative, outdated and unreflective of
      clinical practice in this field. 

PMID- 24575731
TI  - Cesarean section in a high-parity community in Saudi Arabia: clinical indications
      and obstetric outcomes.
AB  - BACKGROUND: The study of the indications for cesarean section (CS) and its
      outcomes are useful for hospitals, clinicians, and researchers in determining
      strategies to lower the primary and repeat CS rate. The aim of this study was to
      identify the indications for CS and the incidence of adverse maternal/fetal
      outcomes in a tertiary care setting. METHODS: A retrospective cohort study of
      women (n = 4305) who gave birth by CS at King Abdulaziz Medical City (KAMC),
      Riyadh, Saudi Arabia (June 2008 to February 2011), was performed. All of the
      women's medical records were reviewed by two consulting physicians to obtain the
      primary indications for CS and determine the maternal characteristics, type of CS
      (emergency or elective), and birth weight. All adverse maternal and fetal
      outcomes were recorded. The point and interval estimates of the odds ratios were
      calculated using a logistic regression model to identify the significant
      predictors of adverse maternal and/or fetal outcomes. RESULTS: Of a total of
      22,595 deliveries from 2008 to 2011, 4,305 deliveries were CS deliveries
      (19.05%). Two-thirds (67%) of all CS deliveries were emergency CSs, and the
      remaining deliveries were elective CSs (33%). Difficult labor (35.9%), fetal
      distress (21.9%) and breech presentation (11.6%) were the most frequent
      indications of emergency CS, while previous CS (54.3%), breech presentation
      (20.4%) and maternal request (10.1%) ranked first for elective CS. Adverse
      maternal and fetal outcomes were diagnosed in 5.09% and 5.06% of deliveries,
      respectively, with a significantly higher incidence in the emergency (6.06% &
      5.51% respectively) than in elective CS (3.10 & 4.16% respectively). Blood
      transfusion was the most frequent adverse maternal outcome (3.72%), followed by
      ICU admission (0.63%), HELLP (0.51%), and hysterectomy (0.30%), while IUGR
      (3.25%) was the most frequent adverse fetal outcome, followed by IUFD and the
      need for ICU admission (0.58% each). Adverse maternal outcomes were significantly
      predicted by high gravidity (OR = 2.84, 95% CI:1.26-6.39, p = 0.011) and
      preeclampsia (OR = 2.84, 95%CI:1.83-4.39, p < 0.001), while adverse fetal
      outcomes were predicted by: twinning (OR = 1.81, p = 0.002), hydramnios (OR =
      6.70, p < 0.001), and preeclampsia (OR = 2.74, p < 0.001). Preterm delivery was a
      significant predictor for both adverse maternal and fetal outcomes (OR = 2.39, p
      < 0.001 & OR = 4.57, p < 0.001, respectively). CONCLUSIONS: Difficult labor and
      previous CS were the main indications for CS in Saudi Arabia. High gravidity was
      a significant predictor of adverse maternal outcomes. Encouraging Saudi women to
      consider embarking on fewer pregnancies could act as a safeguard against
      mandatory CSs for subsequent births in multigravida and grand-multigravida Saudi
      females. Future prospective study that addresses women with repeat CSs and their
      association with adverse maternal and fetal outcomes is recommended.

PMID- 24575732
TI  - Accuracy of genomic predictions in Bos indicus (Nellore) cattle.
AB  - BACKGROUND: Nellore cattle play an important role in beef production in tropical
      systems and there is great interest in determining if genomic selection can
      contribute to accelerate genetic improvement of production and fertility in this
      breed. We present the first results of the implementation of genomic prediction
      in a Bos indicus (Nellore) population. METHODS: Influential bulls were genotyped
      with the Illumina Bovine HD chip in order to assess genomic predictive ability
      for weight and carcass traits, gestation length, scrotal circumference and two
      selection indices. 685 samples and 320 238 single nucleotide polymorphisms (SNPs)
      were used in the analyses. A forward-prediction scheme was adopted to predict the
      genomic breeding values (DGV). In the training step, the estimated breeding
      values (EBV) of bulls were deregressed (dEBV) and used as pseudo-phenotypes to
      estimate marker effects using four methods: genomic BLUP with or without a
      residual polygenic effect (GBLUP20 and GBLUP0, respectively), a mixture model
      (Bayes C) and Bayesian LASSO (BLASSO). Empirical accuracies of the resulting
      genomic predictions were assessed based on the correlation between DGV and dEBV
      for the testing group. RESULTS: Accuracies of genomic predictions ranged from
      0.17 (navel at weaning) to 0.74 (finishing precocity). Across traits, Bayesian
      regression models (Bayes C and BLASSO) were more accurate than GBLUP. The average
      empirical accuracies were 0.39 (GBLUP0), 0.40 (GBLUP20) and 0.44 (Bayes C and
      BLASSO). Bayes C and BLASSO tended to produce deflated predictions (i.e. slope of
      the regression of dEBV on DGV greater than 1). Further analyses suggested that
      higher-than-expected accuracies were observed for traits for which EBV means
      differed significantly between two breeding subgroups that were identified in a
      principal component analysis based on genomic relationships. CONCLUSIONS:
      Bayesian regression models are of interest for future applications of genomic
      selection in this population, but further improvements are needed to reduce
      deflation of their predictions. Recurrent updates of the training population
      would be required to enable accurate prediction of the genetic merit of young
      animals. The technical feasibility of applying genomic prediction in a Bos
      indicus (Nellore) population was demonstrated. Further research is needed to
      permit cost-effective selection decisions using genomic information.

PMID- 24575733
TI  - Predictors in breast cancer screening behaviors of South Asian women.
AB  - AIM: Screening is important in minimizing breast cancer-related morbidity. It is
      prudent to identify the factors that affect women's choice in participation in
      mammographic screening. Our objective was to identify the factors that influence
      the breast screening behaviors in Sri Lankan women. METHODS: Data on referral,
      sociodemographic factors and relevant personal history of all the women visiting
      a single mammography center were prospectively collected during a 4-year period.
      RESULTS: Of the 2695 participants, 1580 had sought mammographic services for
      screening purposes while 1115 were due to symptoms. A majority had Advanced Level
      (AL) or higher education (n = 1570, 58.3%) and were parous. Only a minority had
      past history (n = 221, 8.2%) or family history (n = 357, 13.3%) of breast cancer.
      Majority has normal mammographic findings with detection of 289 (10.7%) benign
      lesions. The mean age was 50.2 years in screening participants, 45.9 years in
      symptomatic women. Use of hormone replacement therapy, age >50 years, AL or
      higher education, having had undergone hysterectomy, past history of breast
      cancer, family history of breast cancer, family history of other cancer and self
      referral were statistically significant contributors to mammography
      participation. In the logistic regression analysis age >50 years, AL or higher
      education, premenopausal status, having undergone hysterectomy and self-referral
      were significantly associated with screening participation and the model
      predicted 72.1% of the cases accurately. CONCLUSION: Five statistically
      significant predictors of mammographic screening among Sri Lankan women were
      identified. These suggest that higher health awareness and exposure to health
      care providers are important predictors.

PMID- 24575735
TI  - Unsafe abortion in the twenty-first century.

PMID- 24575734
TI  - Mechanisms of pulmonary vein reconnection after radiofrequency ablation of atrial
      fibrillation: the deterministic role of contact force and interlesion distance.
AB  - INTRODUCTION: Pulmonary vein reconnection (PVR) is an important cause of AF
      recurrence after ablation. With the advent of force sensing catheters, catheter
      tissue contact can be determined quantitatively. Since contact force (CF) plays a
      major role in determining the characteristics of RF lesion, we prospectively
      assessed the mechanisms of PVR with regard to catheter-contact and lesion
      distances in patients undergoing AF ablation. METHODS AND RESULTS: Forty
      symptomatic AF patients underwent wide circumferential PV isolation (PVI) with
      SmartTouchTM CF catheter. The exact locations of acute PVI and spontaneous or
      adenosine-provoked PVR were annotated on CARTO. One thousand nine hundred and
      twenty-six RF lesions isolated 153 PVs. PVR occurred in 35 (23%) PVs: 22 (63%)
      adenosine-provoked and 13 (37%) spontaneous. CF was significantly lower at PVR
      versus PVI sites for RF lesions within 6 mm from these sites: mean CF 5 versus 11
      g (P < 0.0001) and force-time integral (FTI) 225 versus 415 gs (P < 0.0001); 86%
      of PVR occurred with a mean CF < 10 g (FTI < 400 gs); and the remaining 14%
      occurred at ablation sites with a long interlesion distance (>=5 mm) despite mean
      CF >= 10 g. Eighty percent of PVR sites were located anteriorly. There were no
      significant differences in regard to arrhythmia freedom between the patients
      without (69%) versus with PVR (67%; P = 1.0). CONCLUSIONS: Acutely durable PVI
      can be achieved when RF lesions are delivered with a mean CF >= 10 g and an
      interlesion distance <5 mm. The majority of PVR occur anteriorly due to
      inadequate CF or long interlesion distances.

PMID- 24575736
TI  - Evaluation of serial venous and arterial lactate concentrations in healthy
      anesthetized sheep undergoing ovariectomy.
AB  - OBJECTIVE: To determine if lactate concentrations in jugular venous and auricular
      arterial blood differ in anesthetized sheep. STUDY DESIGN: Prospective,
      controlled experimental study. ANIMALS: Twelve healthy adult ewes, 4-7 years and
      weighing 62-77 kg. METHODS: Jugular venous blood was collected before anesthesia
      (PreOv ) for measurement of lactate concentration, packed cell volume and total
      protein. Ewes were administered a standard anesthesia protocol. Jugular venous
      (IntraOv ) and auricular arterial (IntraOa ) blood samples were obtained 40
      minutes after induction of anesthesia, and again in recovery (PostOv and PostOa
      ). An additional blood sample was drawn 6 weeks post-operatively from non-fasted
      sheep (NF_Lact). Lactate concentrations were compared among PreOv , IntraOv and
      IntraOa , PostOv and PostOa , and between PreOv and NF_Lact with paired t-test
      and repeated measure analyses of variance (anova) with PreOv as a covariate (p <=
      0.05). RESULTS: IntraOv lactate concentration had decreased from PreOv There were
      significant differences between arterial and venous IntraO and PostO lactate
      concentrations. There was no significant difference between IntraO and PostO, or
      PreOv and NF_Lact. CONCLUSIONS AND CLINICAL RELEVANCE: Lactate concentrations
      were significantly lower in anesthetized sheep compared to non-anesthetized
      sheep. Lactate concentrations in venous blood were higher than in arterial blood.
      Therefore, anesthetic status and sampling site should be considered when
      interpreting lactate concentrations, and the sampling site should be consistent
      for repeated measurements.

PMID- 24575738
TI  - Neoadjuvant sirolimus for a large hepatic perivascular epithelioid cell tumor
      (PEComa).
AB  - Perivascular epithelioid cell tumors (PEComas) are rare soft-tissue tumors with
      an extremely heterogeneous clinical behavior. They may arise in different organs
      and may behave indolently or sometimes metastasize with different grades of
      biological aggressiveness. We report the case of a young woman with a primary
      inoperable PEComa of the liver with malignant histological features. Since the
      mTOR pathway is often altered in PEComas and responses have been reported with
      mTOR-inhibitors such as sirolimus or temsirolimus, we decided to start a
      neoadjuvant treatment with sirolimus. The patient tolerated the treatment fairly
      well and after 8 months a favorable tumor shrinkage was obtained. The patient
      then stopped sirolimus and 2 weeks later underwent partial liver resection, with
      complete clinical recovery and normal liver function. The histological report
      confirmed a malignant PEComa with vascular invasion and negative margins. Then 6
      additional months of post-operative sirolimus treatment were administered,
      followed by regular radiological follow-up. For patients with a large and
      histologically aggressive PEComa, we think that neoadjuvant treatment with mTOR
      inhibitor sirolimus may be considered to facilitate surgery and allow early
      control of a potentially metastatic disease. For selected high-risk patients, the
      option of adjuvant treatment may be discussed.

PMID- 24575737
TI  - Key considerations for the experimental training and evaluation of cancer odour
      detection dogs: lessons learnt from a double-blind, controlled trial of prostate
      cancer detection.
AB  - BACKGROUND: Cancer detection using sniffer dogs is a potential technology for
      clinical use and research. Our study sought to determine whether dogs could be
      trained to discriminate the odour of urine from men with prostate cancer from
      controls, using rigorous testing procedures and well-defined samples from a major
      research hospital. METHODS: We attempted to train ten dogs by initially rewarding
      them for finding and indicating individual prostate cancer urine samples (Stage
      1). If dogs were successful in Stage 1, we then attempted to train them to
      discriminate prostate cancer samples from controls (Stage 2). The number of
      samples used to train each dog varied depending on their individual progress.
      Overall, 50 unique prostate cancer and 67 controls were collected and used during
      training. Dogs that passed Stage 2 were tested for their ability to discriminate
      15 (Test 1) or 16 (Tests 2 and 3) unfamiliar prostate cancer samples from 45
      (Test 1) or 48 (Tests 2 and 3) unfamiliar controls under double-blind conditions.
      RESULTS: Three dogs reached training Stage 2 and two of these learnt to
      discriminate potentially familiar prostate cancer samples from controls. However,
      during double-blind tests using new samples the two dogs did not indicate
      prostate cancer samples more frequently than expected by chance (Dog A
      sensitivity 0.13, specificity 0.71, Dog B sensitivity 0.25, specificity 0.75).
      The other dogs did not progress past Stage 1 as they did not have optimal
      temperaments for the sensitive odour discrimination training. CONCLUSIONS:
      Although two dogs appeared to have learnt to select prostate cancer samples
      during training, they did not generalise on a prostate cancer odour during robust
      double-blind tests involving new samples. Our study illustrates that these
      rigorous tests are vital to avoid drawing misleading conclusions about the
      abilities of dogs to indicate certain odours. Dogs may memorise the individual
      odours of large numbers of training samples rather than generalise on a common
      odour. The results do not exclude the possibility that dogs could be trained to
      detect prostate cancer. We recommend that canine olfactory memory is carefully
      considered in all future studies and rigorous double-blind methods used to avoid
      confounding effects.

PMID- 24575739
TI  - An aza-macrocycle containing maltolic side-arms (maltonis) as potential drug
      against human pediatric sarcomas.
AB  - BACKGROUND: Identification of new drugs against paediatric sarcomas represents an
      urgent clinical need that mainly relies on public investments due to the rarity
      of these diseases. In this paper we evaluated the in vitro and in vivo efficacy
      of a new maltol derived molecule (maltonis), belonging to the family of molecules
      named hydroxypyrones. METHODS: Maltonis was screened for its ability to induce
      structural alteration of DNA molecules in comparison to another maltolic molecule
      (malten). In vitro antitumour efficacy was tested using a panel of sarcoma cell
      lines, representative of Ewing sarcoma, osteosarcoma and rhabdomyosarcoma, the
      three most common paediatric sarcomas, and in normal human mesenchymal primary
      cell cultures. In vivo efficacy was tested against TC-71 Ewing sarcoma
      xenografts. RESULTS: Maltonis, a soluble maltol-derived synthetic molecule, was
      able to alter the DNA structure, inhibit proliferation and induce apoptotic cell
      death in paediatric sarcoma cells, either sensitive or resistant to some
      conventional chemotherapeutic drugs, such as doxorubicin and cisplatin. In
      addition, maltonis was able to induce: i) p21, p15 and Gadd45a mRNA upregulation;
      ii) Bcl-2, survivin, CDK6 and CDK8 down-regulation; iii) formation of gamma-H2AX
      nuclear foci; iv) cleavage of PARP and Caspase 3. Two independent in vivo
      experiments demonstrated the tolerability and efficacy of maltonis in the
      inhibition of tumour growth. Finally maltonis was not extruded by ABCB1, one of
      the major determinants of chemotherapy failure, nor appeared to be a substrate of
      the glutathione-related detoxification system. CONCLUSIONS: Considering that
      treatment of poorly responsive patients still suffers for the paucity of agents
      able to revert chemoresistance, maltonis may be considered for the future
      development of new therapeutic approaches for refractory metastatic patients.

PMID- 24575740
TI  - Lifespan differences in cortico-striatal resting state connectivity.
AB  - Distinctive cortico-striatal circuits that serve motor and cognitive functions
      have been recently mapped based on resting state connectivity. It has been
      reported that age differences in cortico-striatal connectivity relate to
      cognitive declines in aging. Moreover, children in their early teens (i.e.,
      youth) already show mature motor network patterns while their cognitive networks
      are still developing. In the current study, we examined age differences in the
      frontal-striatal "cognitive" and "motor" circuits in children and adolescence,
      young adults (YAs), and older adults (OAs). We predicted that the strength of the
      "cognitive" frontal-striatal circuits would follow an inverted "U" pattern across
      age; children and OAs would have weaker connectivity than YAs. However, we
      predicted that the "motor" circuits would show less variation in connectivity
      strength across the lifespan. We found that most areas in both the "cognitive"
      and "motor" circuits showed higher connectivity in YAs than children and OAs,
      suggesting general inverted "U"-shaped changes across the lifespan for both the
      cognitive and motor frontal-striatal networks.

PMID- 24575741
TI  - Intra-abdominal pressures during activity in women using an intra-vaginal
      pressure transducer.
AB  - Strenuous physical activity has been linked to pelvic floor disorders in women.
      Using a novel wireless intra-vaginal pressure transducer, intra-abdominal
      pressure was measured during diverse activities in a laboratory. Fifty-seven
      women performed a prescribed protocol using the intra-vaginal pressure
      transducer. We calculated maximal, area under the curve and first moment of the
      area intra-abdominal pressure for each activity. Planned comparisons of pressure
      were made between levels of walking and cycling and between activities with
      reported high pressure in the literature. Findings indicate variability in intra
      abdominal pressure amongst individuals doing the same activity, especially in
      activities that required regulation of effort. There were statistically
      significant differences in maximal pressure between levels of walking, cycling
      and high pressure activities. Results for area under the curve and first moment
      of the area were not always consistent with maximal pressure. Coughing had the
      highest maximal pressure, but had lower area under the curve and first moment of
      the area compared to most activities. Our data reflect novel findings of maximal,
      area under the curve and first moment of the area measures of intra-abdominal
      pressure, which may have clinical relevance for how physical activity relates to
      pelvic floor dysfunction.

PMID- 24575742
TI  - Isolation of sindbis virus from a hooded crow in Germany.
AB  - Sindbis virus (SINV) is an arbovirus that causes clinical symptoms, including
      arthritis, rash, and fever during acute human infections. In Europe, SINV
      outbreaks are largely restricted to northern Europe. Intrigued by the isolation
      of SINV from mosquitoes in southwestern Germany in 2009, we initiated a passive
      arbovirus-monitoring program in birds and analyzed a total of 685 samples. By
      this approach, we were able to detect a SINV in a Hooded Crow in Germany for the
      first time. It was possible to isolate SINV virus in cell cultures and even to
      visualize virus particles by electron microscopy. After the determination of the
      complete SINV genome sequence, the phylogenetic analysis revealed its close
      relationship to SINV genotype I sequences previously obtained from mosquitoes in
      Germany and Scandinavia. This first report on the isolation of viable SINV
      indicates the potential involvement of crows in an enzootic circulation of SINV
      in Germany and Central Europe.

PMID- 24575746
TI  - Four lenses through which to develop wellness incentive policies.
AB  - Employers had to scramble to develop policies for their Wellness Incentives in
      time for their Fall, 2013 Open Enrollment deadlines, and are already refining
      policies for the 2014 Open Enrollment period. Employers are encouraged to
      consider six policy elements and to view all of them through four lenses. The
      policy elements are: (1) Number and Types of Behaviors and Outcomes to Target.
      (2) Cost-Positive, Neutral, or Savings Approach. (3) Maximum Incentive Value and
      Allocation of Incentives. (4) Ratio of Types of Incentive Structure for
      Reasonable Alternative Standards. (5) Numbers of Cycles of RASs. (6) Access and
      Allocations for Family Members. The lenses are: (1) What drives healthy behavior?
      (2) What is equitable? (3) What is sustainable? and (4) What enhances employee
      morale? 

PMID- 24575743
TI  - Classification of the alveolar ridge width: implant-driven treatment
      considerations for the horizontally deficient alveolar ridges.
AB  - Among many techniques advocated for the horizontally deficient alveolar ridges,
      ridge-split has many advantages. Here, treatment management strategies of the
      horizontally collapsed ridges, especially the ridge-split approach, are discussed
      and a clinically relevant implant-driven classification of the alveolar ridge
      width is proposed, with the goal to assist an operator in choosing the proper
      bone augmentation technique. Comparison and advantages of two commonly used
      techniques, ridge-split and block bone graft, are presented. 

PMID- 24575747
TI  - Editor's desk: the measurement issue.

PMID- 24575748
TI  - A large esophageal gastrointestinal stromal tumor that was successfully resected
      after neoadjuvant imatinib treatment: case report.
AB  - A 49-year-old man was admitted to our hospital with a 1-month history of
      dysphagia. An upper endoscopy revealed a lower esophageal submucosal tumor.
      Immunohistochemical staining of the biopsy specimen revealed KIT positivity.
      Thus, the tumor was diagnosed as a gastrointestinal stromal tumor (GIST). After 6
      months of imatinib treatment, the tumor decreased from 92 mm * 55 mm * 80 mm to
      65 mm * 35 mm * 55 mm in diameter, and surgery was performed. The tumor was
      completely resected without rupture, by partial esophagogastric resection through
      a thoracotomy incision, using an abdominal laparoscopic approach.
      Immunohistochemical staining revealed that the tumor was negative for c-kit but
      positive for CD34. Genetic examination showed that the tumor had a mutation in
      exon 11. The patient experienced minor leakage but recovered conservatively.
      Adjuvant imatinib was initiated 64 days after surgery. We report this rare case
      to show the potential of preoperative imatinib treatment in patients with large
      esophageal GISTs, to achieve complete resection without rupture.

PMID- 24575749
TI  - Stage and tissue-specific prognostic impact of miR-182 in NSCLC.
AB  - BACKGROUND: MicroRNA (miR)-182 is frequently upregulated in cancers, has
      generally been viewed as an oncogene and is possibly connected to angiogenesis.
      We aimed to explore what impact miR-182 has in non-small cell lung cancer
      (NSCLC), and more explicitly its correlation with angiogenic markers. METHODS:
      From 335 unselected stage I to IIIA NSCLC carcinomas, duplicate tumor and tumor
      associated stromal cores were collected in tissue microarray blocks (TMAs). In
      situ hybridization (ISH) was used to detect the expression of miR-182 in tumor
      cells, and immunohistochemistry (IHC) was used to detect the expression of
      angiogenesis related protein markers. RESULTS: In univariate analyses, high tumor
      cell expression of miR-182 was a positive prognostic factor for patients with
      squamous cell carcinoma (SCC, P = 0.042) and stage II patients (P = 0.003). Also
      in the multivariate analysis, high tumor cell miR-182 expression was associated
      with a good prognosis in the same groups (SCC: HR 0.57, CI 95% 0.33-0.99, P =
      0.048; stage II: HR 0.50, CI 95% 0.28-0.90, P = 0.020). We found significant
      correlations between miR-182 and the angiogenesis related markers FGF2, HIF2alpha
      and MMP-7. CONCLUSION: In patients with SCC and in stage II patients, high tumor
      cell miR-182 expression is an independent positive prognostic factor.

PMID- 24575750
TI  - Pharmacological characteristics and efficacy of a novel anti-angiogenic antibody
      FD006 in corneal neovascularization.
AB  - BACKGROUND: Vascular endothelial growth factor (VEGF) is a key angiogenic
      factors. It plays an important role in both physiologic and pathologic
      angiogenesis and increases permeability across the vessels. Using antibody phage
      display technology, we obtained a novel anti-VEGFA IgG, named as FD006. In this
      study, the pharmacological characteristics and efficacy of FD006 in corneal
      neovascularization (CoNV) were evaluated. RESULTS: FD006 was predicted to have
      similar binding mode to bevacizumab. Experimental analysis showed that the
      binding ability of FD006 seemed a little stronger than bevacizumab, for the EC50
      of FD006 to bind VEGF analyzed by ELISA was about 0.037 MUg/mL while that of
      bevacizumab was 0.18 MUg/mL. Binding kinetics assays showed similar results that
      FD006 possessed 2-fold higher affinity to bind VEGF than bevacizumab due to
      slower dissociation rate of FD006; meanwhile, FD006 inhibited the VEGF-induced
      proliferation of HUVEC with an IC50 value of 0.031 +/- 0.0064 MUg/ml, which
      seemed similar or a litter better than bevacizumab (0.047 +/- 0.0081 MUg/ml). The
      subconjunctival administration of FD006, bevacizumab or dexamethasone could
      significantly inhibit the growth of CoNV contrasting to N.S (p < 0.01). At the
      early stage, FD006 showed better inhibitory effect on the growth of CoNV compared
      with bevacizumab (p < 0.05). Western blot analysis showed that FD006 could
      inhibit the expression of VEGF, VEGFR-1, VEGFR-2, MMP-9 and ICAM-1, which could
      explain its favorable anti-angiogenic activity. CONCLUSIONS: The pharmacological
      characteristics of FD006 were similar or even a little better than bevacizumab in
      inhibiting corneal neovascularization.

PMID- 24575751
TI  - Analysing RNA-kinetics based on folding space abstraction.
AB  - BACKGROUND: RNA molecules, especially non-coding RNAs, play vital roles in the
      cell and their biological functions are mostly determined by structural
      properties. Often, these properties are related to dynamic changes in the
      structure, as in the case of riboswitches, and thus the analysis of RNA folding
      kinetics is crucial for their study. Exact approaches to kinetic folding are
      computationally expensive and, thus, limited to short sequences. In a previous
      study, we introduced a position-specific abstraction based on helices which we
      termed helix index shapes (hishapes) and a hishape-based algorithm for near
      optimal folding pathway computation, called HiPath. The combination of these
      approaches provides an abstract view of the folding space that offers information
      about the global features. RESULTS: In this paper we present HiKinetics, an
      algorithm that can predict RNA folding kinetics for sequences up to several
      hundred nucleotides long. This algorithm is based on RNAHeliCes, which decomposes
      the folding space into abstract classes, namely hishapes, and an improved version
      of HiPath, namely HiPath2, which estimates plausible folding pathways that
      connect these classes. Furthermore, we analyse the relationship of hishapes to
      locally optimal structures, the results of which strengthen the use of the
      hishape abstraction for studying folding kinetics. Finally, we show the
      application of HiKinetics to the folding kinetics of two well-studied RNAs.
      CONCLUSIONS: HiKinetics can calculate kinetic folding based on a novel hishape
      decomposition. HiKinetics, together with HiPath2 and RNAHeliCes, is available for
      download at http://www.cyanolab.de/software/RNAHeliCes.htm.

PMID- 24575752
TI  - Combining spatial independent component analysis with regression to identify the
      subcortical components of resting-state FMRI functional networks.
AB  - Functional brain networks are sets of cortical, subcortical, and cerebellar
      regions whose neuronal activities are synchronous over multiple time scales.
      Spatial independent component analysis (sICA) is a widespread approach that is
      used to identify functional networks in the human brain from functional magnetic
      resonance imaging (fMRI) resting-state data, and there is now a general agreement
      regarding the cortical regions involved in each network. It is well known that
      these cortical regions are preferentially connected with specific subcortical
      functional territories; however, subcortical components (SC) have not been
      observed whether in a robust or in a reproducible manner using sICA. This article
      presents a new method to analyze resting-state fMRI data that enables robust and
      reproducible association of subcortical regions with well-known patterns of
      cortical regions. The approach relies on the hypothesis that the time course in
      subcortical regions is similar to that in cortical regions belonging to the same
      network. First, sICA followed by hierarchical clustering is performed on cortical
      time series to extract group functional cortical networks. Second, these networks
      are complemented with related subcortical areas based on the similarity of their
      time courses, using an individual general linear model and a random-effect group
      analysis. Two independent resting-state fMRI datasets were processed, and the SC
      of both datasets overlapped by 69% to 99% depending on the network, showing the
      reproducibility and the robustness of our approach. The relationship between SC
      and functional cortical networks was consistent with functional territories
      (sensorimotor, associative, and limbic) from an immunohistochemical atlas of the
      basal ganglia.

PMID- 24575753
TI  - Dynamics of the support leg in soccer instep kicking.
AB  - We aimed to illustrate support leg dynamics during instep kicking to evaluate the
      role of the support leg action in performance. Twelve male soccer players
      performed maximal instep kicks. Their motions and ground reaction forces were
      recorded by a motion capture system and a force platform. Moments and angular
      velocities of the support leg and pelvis were computed using inverse dynamics. In
      most joints of the support leg, the moments were not associated with or
      counteracting the joint motions except for the knee joint. It can be interpreted
      that the initial knee flexion motion counteracting the extension joint moment has
      a role to attenuate the shock of landing and the following knee extension motion
      associated with the extension joint moment indirectly contributes to accelerate
      the swing of kicking leg. Also, appreciable horizontal rotation of the pelvis
      coincided with increase of the interaction moment due to the hip joint reaction
      force on the support leg side. It can be assumed that the interaction moment was
      the main factor causing the pelvis counter-clockwise rotation within the
      horizontal plane from the overhead view that precedes a proximal-to-distal
      sequence of segmental action of the swing leg.

PMID- 24575756
TI  - Rhodium(II)-catalyzed stereocontrolled synthesis of dihydrofuran-3-imines from 1
      tosyl-1,2,3-triazoles.
AB  - Rhodium(II) acetate catalyzes the denitrogenative transformation of 5-substituted
      and 4,5-disubstituted 1-sulfonyl-1,2,3-triazoles with pendent allyl and propargyl
      ether motifs to oxonium ylides that undergo [2,3]-sigmatropic rearrangement to
      give substituted dihydrofuran-3-imines in high yield and diastereoselectivity. 

PMID- 24575754
TI  - Catalytic enantioselective cyclization/cross-coupling with alkyl electrophiles.
AB  - As part of our ongoing effort to expand the scope of cross-coupling reactions of
      alkyl electrophiles, we have pursued a strategy wherein the nucleophilic coupling
      partner includes a pendant olefin; after transmetalation by such a substrate, if
      beta-migratory insertion proceeds faster than direct cross-coupling, an
      additional carbon-carbon bond and stereocenter can be formed. With the aid of a
      nickel/diamine catalyst (both components are commercially available), we have
      established the viability of this approach for the catalytic asymmetric synthesis
      of 2,3-dihydrobenzofurans and indanes. Furthermore, we have applied this new
      method to the construction of the dihydrobenzofuran core of fasiglifam, as well
      as to a cross-coupling with a racemic alkyl electrophile; in the latter process,
      the chiral catalyst controls two stereocenters, one that is newly generated in a
      beta-migratory insertion and one that begins as a mixture of enantiomers. 

PMID- 24575755
TI  - Anjozorobe hantavirus, a new genetic variant of Thailand virus detected in
      rodents from Madagascar.
AB  - Until now, there was only serological evidence that hantaviruses were circulating
      in rodents and infecting humans from Madagascar. To assess the presence of a
      hantavirus on the island, between October, 2008, and March, 2010, we sampled 585
      rodents belonging to seven species in the Anjozorobe-Angavo forest corridor, 70
      km north from the capital city Antananarivo. A hantavirus was detected from
      organs of the ubiquist roof rat (Rattus rattus) and of the endemic Major's tufted
      tailed rat (Eliurus majori). Amazingly, sequence analysis of the S (small), M
      (medium), and L (large) coding DNA sequence of this virus showed that the
      Anjozorobe strain (proposed name) was a new genetic variant of Thailand virus
      (THAIV) that comprises other variants found in Southeast Asia. Because THAIV is
      suspected of causing hemorrhagic fever with renal syndrome in humans, ongoing
      studies are addressing the risk of infection by this new variant in the Malagasy
      population.

PMID- 24575757
TI  - Factors Associated With Crestal Bone Loss Following Dental Implant Placement in a
      Longitudinal Follow-up Study.
AB  - The purpose of this study is to estimate the magnitude of crestal bone loss and
      to identify factors associated with changes in crestal bone height following
      placement of dental implants. This was a retrospective cohort study, consisting
      of a sample derived from the population of patients who had at least 1 dental
      implant placed in a community practice over a 10-year period. A total of 11
      predictor variables were grouped into demographic, related health status,
      anatomic, implant-specific, and operative categories. The primary outcome
      variable was a change in crestal bone height (mm) over the course of follow-up.
      The secondary outcome variable was crestal bone loss at 1 year grouped into 2
      categories (bone loss >1.5 mm and <=1.5 mm). Univariate and multivariate
      regression mixed-effects models were developed to identify variables associated
      with crestal bone level changes over time. P values <=.05 were considered
      statistically significant. The study sample was composed of 85 subjects who
      received 148 implants. The mean change of the crestal bone was -2.1 +/- 1.5 mm
      (range = -12.5 to 0.5 mm; median = -1.77 mm). In the multivariate model, none of
      the variables studied were statistically associated with mean crestal bone loss.
      Among 84 (66.1%) implants with bone loss >1.5 mm within 1 year, no variables were
      associated with bone loss in the multivariate model. Of the 11 predictor
      variables evaluated in this study, none were statistically significant with
      regard to an increased risk for crestal bone loss or for excessive bone loss
      within the first year after implant placement. 

PMID- 24575758
TI  - An inventory of reasons for sperm donation in formal versus informal settings.
AB  - The shortage of sperm donors in formal settings (i.e., assisted reproduction
      clinics) and the availability of sperm donors in informal settings (such as
      through contacts on the internet) motivated us to investigate why men may prefer
      either a formal or an informal setting for sperm donation. Interviews with ten
      sperm donors and non-sperm donors yielded 55 reasons for sperm donation in the
      two settings. These reasons were categorized according to similarity by 14 sperm
      donors and non-sperm donors. These categorizations were then structured by means
      of hierarchical cluster analysis. Reasons favouring formal settings included
      being legally and physically protected, evading paternal feelings or social
      consequences, and having a simple, standardized procedure in terms of effort and
      finances. Reasons favouring informal settings related to engagement, the
      possibility to choose a recipient, lack of rules and regulations, having contact
      with the donor child, and having an (intimate) bond with the recipient. The
      overview of reasons identified may help potential sperm donors decide on whether
      to donate in a formal or informal setting, and may fuel discussions by
      professionals about the most appropriate conditions and legislation for sperm
      donation in formal settings.

PMID- 24575767
TI  - Awareness of chronic disease related health benefits of physical activity among
      residents of a rural South Indian region: a cross-sectional study.
AB  - BACKGROUND: Physical activity trends for a lower-middle income country like India
      suggest a gradual decline in work related physical activity and no concomitant
      increase in leisure time physical activity. Perceived health benefits of physical
      activity and intention to increase physical activity have been established as
      independent correlates of physical activity status. In India, not much is known
      about peoples' perceptions of health benefits of physical activity and their
      intention to increase physical activity levels. This study was performed to
      understand peoples' perceptions and awareness about health benefits of physical
      activity in a rural South Indian region. METHODS: This cross-sectional study was
      conducted using a multistage cluster sampling design. A content validated, field
      tested questionnaire was administered in person by a trained interviewer in the
      participants' native language. The questionnaire assessed the participants'
      perceptions about their lifestyle (active or sedentary), health benefits of
      physical activity and need for increasing their physical activity. In addition,
      the participant's physical activity was assessed using version 2 of global
      physical activity questionnaire. Frequencies and percentages were used to
      summarise perceived health benefits of physical activity and other categorical
      variables. Age and body mass index were summarised using mean +/- SD, whereas
      physical activity (MET.min.wk -1) was summarised using median and interquartile
      range. RESULTS: Four hundred fifty members from 125 randomly selected households
      were included in the study, of which 409 members participated. 89% (364) of
      participants felt they lead an active lifestyle and 83.1% (340) of participants
      did not feel a need to increase their physical activity level. 86.1%, (352) of
      the participants were physically active. Though 92.4% (378) of participants felt
      there were health benefits of physical activity, majority of them (75.1%) did not
      report any benefit related to chronic diseases. None mentioned health benefits
      related to heart disease or stroke. CONCLUSION: There is low awareness of chronic
      disease related benefits of physical activity and participants do not see a need
      to increase their physical activity level. Public health awareness programs on
      importance and health benefits of physical activity would be useful to counter
      the anticipated decline in physical activity.

PMID- 24575766
TI  - Co-expressed mitochondrial genomes: recently masculinized, recombinant
      mitochondrial genome is co-expressed with the female-transmitted mtDNA genome in
      a male Mytilus trossulus mussel from the Baltic Sea.
AB  - BACKGROUND: Few exceptions have been described from strict maternal inheritance
      of mitochondrial DNA in animals, including sea mussels (Mytilidae), clams
      (Donacidae, Veneridae and Solenidae) and freshwater mussels (Unionoidae) order.
      In these bivalves mitochondria and their DNA are transferred through two separate
      routes. The females inherit only the maternal mitochondrial DNA whereas the males
      inherit maternal as well as paternal mitochondrial DNA, which is usually present
      only in gonads and sperm. The mechanism controlling this phenomenon is unclear
      but leads to the existence of two separate mitochondrial DNA lineages in a single
      species. The lineages are usually well differentiated: up to 20-50% divergence in
      nucleotide sequence. Occasionally, a maternal mitochondrial DNA can invade the
      paternal transmission route, eventually replacing the diverged M-type and
      lowering the divergence. Such role reversal (masculinization) event has happened
      recently in the Mytilus population of the Baltic Sea which consists of M. edulis
      * M. trossulus hybrids, but the functional status of the resulting mitochondrial
      genome was unknown. RESULTS: In this paper we sequenced transcripts from one
      specimen that was identified as male carrying both the female mitochondrial
      genome and a recently masculinized mitochondrial genome. Additionally, the
      analysis of the control region has showed that the recently masculinized,
      recombinant genome, not only has an M-type control region and all coding regions
      derived from the F-type, but also is transcriptionally active along side the
      maternally inherited F-type genome. In the comparative analysis, the two genomes
      exhibit different substitution patterns, typical for the M vs. F genome
      comparisons. The genetic distances and ratios of non-synonymous substitutions
      also suggest that one of the genomes is transitioning from the maternal to the
      paternal inheritance mode, consistent with its recent masculinization.
      CONCLUSION: We have shown, for the first time, that the recently masculinized
      mitochondrial genome is active and that it accumulates excess of non-synonymous
      substitutions across its coding sequence. This suggests, that, under certain
      cytonuclear incompatibility conditions, masculinization may serve to restore the
      endangered functionality of the paternally inherited genome. This is also another
      example of a mitochondrial genome in which the recombination in the control
      region predated its transition from paternal to maternal transmission route.

PMID- 24575769
TI  - Transversus abdominis plane block after ambulatory total laparoscopic
      hysterectomy: randomized controlled trial.
AB  - OBJECTIVE: To determine if transversus abdominis plane anesthetic blockage (TAP
      block) diminishes early postoperative pain scores and facilitates ambulatory
      management following total laparoscopic hysterectomy. DESIGN: Randomized triple
      blind trial. SETTING: Gynecological endoscopy unit at a referral center for
      laparoscopic surgery. POPULATION: A total of 197 patients. METHODS: Comparison of
      a treatment group receiving TAP block with bupivacaine 0.25% and placebo group
      with comparably placed bilateral injection of sterile saline solution. MAIN
      OUTCOME MEASURES: Pain scores at discharge 24, 48 and 72 h after surgery, opioid
      requirement after procedure. RESULTS: Patients who had TAP block had a
      significant reduction in their pain score at discharge compared with the placebo
      group (p = 0.017). There were no significant differences in the pain scores
      between groups at 24 h (95% CI 1.36-0.133, p = 0.237), 48 h (95% CI 0.689-0.465,
      p = 0.702) and 72 h (95% CI -0.631 to 0.223, p = 0.347). No differences were
      found between the groups regarding opioid requirements following the procedure
      (chi(2)  = 3.62, p = 0.46). CONCLUSION: Although TAP block after a total
      laparoscopic hysterectomy reduced the pain score at discharge compared with
      placebo, its role in this setting is debatable due to the possible lack of
      clinical significance of the small difference found.

PMID- 24575768
TI  - Adrenocortical insufficiency is not a problem in preterm infants treated with
      antifungal prophylaxis with fluconazole.
AB  - AIM: Fluconazole prophylaxis of invasive fungal infections is a cornerstone of
      neonatal care, but in vitro studies have shown that it inhibits corticosteroid
      production. This study assessed whether preterm infants demonstrated an
      association between fluconazole administration, and its duration, and symptoms of
      adrenocortical insufficiency. METHODS: We compared two groups who were treated
      before and after we introduced the use of fluconazole to our neonatal intensive
      care unit. Infants with a gestational age of <=27 weeks or with a birth weight of
      <=750 g were considered for the retrospective analysis. In order to assess
      whether the duration of prophylaxis was related to adrenocortical insufficiency,
      regression models were performed in all preterm infants in the fluconazole group.
      RESULTS: The fluconazole group (n = 37) and nonfluconazole group (n = 41) were
      compared. No differences were found in the percentage of infants with symptoms of
      adrenocortical insufficiency, such as hypotension or need of vasopressor therapy.
      The incidence of hypotension and the use of vasopressor therapy were not related
      to duration of fluconazole prophylaxis. CONCLUSION: Fluconazole and it duration
      were not associated with the incidence of symptoms related to adrenocortical
      insufficiency. Further prospective trials are needed to better define the
      relationship between fluconazole and adrenocortical insufficiency.

PMID- 24575770
TI  - American Geriatrics Society identifies another five things that healthcare
      providers and patients should question.
AB  - Since 2012, the American Geriatrics Society (AGS) has also been collaborating
      with the American Board of Internal Medicine (ABIM) Foundation, joining its
      "Choosing Wisely" campaign on two separate lists of Five Things Healthcare
      Providers and Patients Should Question. The campaign is designed to engage
      healthcare organizations and professionals, individuals, and family caregivers in
      discussions about the safety and appropriateness of medical tests, medications,
      and procedures. Participating healthcare providers are asked to identify five
      things-tests, medications, or procedures-that appear to harm rather than help.
      Providers then share this information in a published article about these things
      on the ABIM campaign's website (www.choosingwisely.org). The first AGS list was
      published in February 2013. 

PMID- 24575772
TI  - EGFR gene mutations in patients with adenosquamous lung carcinoma.
AB  - AIM: Adenosquamous (ADSQ) carcinoma accounts for 1-4% of non-small cell lung
      cancer (NSCLC). The origin of ADSQ carcinoma and its genetic background is not
      fully understood. Most studies concerning epidermal growth factor receptor (EGFR)
      mutation status are performed in adenocarcinoma, while there is limited
      information about the prevalence of this mutation in ADSQ-bearing Caucasian
      patients and the efficacy of EGFR tyrosine kinase inhibitors. METHODS: EGFR gene
      status has been examined in 1000 non-squamous NSCLC patients of Polish origin.
      Polymerase chain reaction (PCR) followed by DNA fragment length analysis and
      allele-specific PCR as well as real-time PCR technique were used to estimate EGFR
      gene status. Complete clinical data were obtained for all examined patients.
      RESULTS: In the group of 1000 non-squamous NSCLC patients, ADSQ was diagnosed in
      14 (1.4%) cases. Activating mutations of EGFR were observed in 28.6% (four out of
      14) of ADSQ-bearing patients and included deletions of 15 base-pairs in exon 19
      in three cases (one man and two women) and substitution of L861Q with coexistence
      of G719X mutation in one non-smoking male patient. Deletions were diagnosed in
      two non-smoking patients and one current-smoking female patient (50 pack-years).
      One non-smoking man with deletion in exon 19 of EGFR gene was successfully
      treated with gefitinib in first-line therapy. CONCLUSIONS: EGFR gene mutations in
      ADSQ carcinoma patients may be more common than previously thought. EGFR mutation
      testing is appropriate in ADSQ-bearing patients, in which response for molecular
      based therapy is predictable.

PMID- 24575773
TI  - What happens to plant mitochondria under low oxygen? An omics review of the
      responses to low oxygen and reoxygenation.
AB  - Floods can rapidly submerge plants, limiting oxygen to the extent that oxidative
      phosphorylation no longer generates adequate ATP supplies. Low-oxygen tolerant
      plants, such as rice, are able to adequately respond to low oxygen by
      successfully remodelling primary and mitochondrial metabolism to partially
      counteract the energy crisis that ensues. In this review, we discuss how plants
      respond to low-oxygen stress at the transcriptomic, proteomic, metabolomic and
      enzyme activity levels, particularly focusing on mitochondria and interacting
      pathways. The role of reactive oxygen species and nitrite as an alternative
      electron acceptor as well as their links to respiratory chain components is
      discussed. By making intra-kingdom as well as cross-kingdom comparisons,
      conserved mechanisms of anoxia tolerance are highlighted as well as tolerance
      mechanisms that are specific to anoxia-tolerant rice during germination and in
      coleoptiles. We discuss reoxygenation as an often overlooked, yet essential stage
      of this environmental stress and consider the possibility that changes occurring
      during low oxygen may also provide benefits upon re-aeration. Finally, we
      consider what it takes to be low-oxygen tolerant and argue that alternative
      mechanisms of ATP production, glucose signalling, starch/sucrose signalling as
      well as reverse metabolism of fermentation end products promote the survival of
      rice after this debilitating stress. 

PMID- 24575774
TI  - Reduced medial prefrontal-subcortical connectivity in dysphoria: Granger
      causality analyses of rapid functional magnetic resonance imaging.
AB  - A cortico-limbic network consisting of the amygdala, medial prefrontal cortex
      (mPFC), and ventral striatum (vSTR) has been associated with altered function in
      emotional disorders. Here we used rapidly sampled functional magnetic resonance
      imaging and Granger causality analyses to assess the directional connectivity
      between these brain structures in a sample of healthy and age-matched
      participants endorsing moderate to severe depressive symptomatology as they
      viewed a series of natural scene stimuli varying systematically in pleasantness
      and arousal. Specifically during pleasant scene perception, dysphoric
      participants showed reduced activity in mPFC and vSTR, relative to healthy
      participants. In contrast, amygdala activity was enhanced to pleasant as well as
      unpleasant arousing scenes in both participant groups. Granger causality
      estimates of influence between mPFC and vSTR were significantly reduced in
      dysphoric relative to control participants during all picture contents. These
      findings provide direct evidence that during visual perception of evocative
      emotional stimuli, reduced reward-related activity in dysphoria is associated
      with dysfunctional causal connectivity between mPFC, amygdala, and vSTR. 

PMID- 24575771
TI  - Pharmacological inhibition of EZH2 as a promising differentiation therapy in
      embryonal RMS.
AB  - BACKGROUND: Embryonal Rhabdomyosarcoma (RMS) is a pediatric soft-tissue sarcoma
      derived from myogenic precursors that is characterized by a good prognosis in
      patients with localized disease. Conversely, metastatic tumors often relapse,
      leading to a dismal outcome. The histone methyltransferase EZH2 epigenetically
      suppresses skeletal muscle differentiation by repressing the transcription of
      myogenic genes. Moreover, de-regulated EZH2 expression has been extensively
      implied in human cancers. We have previously shown that EZH2 is aberrantly over
      expressed in RMS primary tumors and cell lines. Moreover, it has been recently
      reported that EZH2 silencing in RD cells, a recurrence-derived embryonal RMS cell
      line, favors myofiber-like structures formation in a pro-differentiation context.
      Here we evaluate whether similar effects can be obtained also in the presence of
      growth factor-supplemented medium (GM), that mimics a pro-proliferative
      microenvironment, and by pharmacological targeting of EZH2 in RD cells and in RD
      tumor xenografts. METHODS: Embryonal RMS RD cells were cultured in GM and
      silenced for EZH2 or treated with either the S-adenosylhomocysteine hydrolase
      inhibitor 3-deazaneplanocin A (DZNep) that induces EZH2 degradation, or with a
      new class of catalytic EZH2 inhibitors, MC1948 and MC1945, which block the
      catalytic activity of EZH2. RD cell proliferation and myogenic differentiation
      were evaluated both in vitro and in vivo. RESULTS: Here we show that EZH2 protein
      was abnormally expressed in 19 out of 19 (100%) embryonal RMS primary tumors and
      cell lines compared to their normal counterparts. Genetic down-regulation of EZH2
      by silencing in GM condition reduced RD cell proliferation up-regulating p21Cip1.
      It also resulted in myogenic-like differentiation testified by the up-regulation
      of myogenic markers Myogenin, MCK and MHC. These effects were reverted by
      enforced over-expression of a murine Ezh2, highlighting an EZH2-specific effect.
      Pharmacological inhibition of EZH2 using either DZNep or MC inhibitors
      phenocopied the genetic knockdown of EZH2 preventing cell proliferation and
      restoring myogenic differentiation both in vitro and in vivo. CONCLUSIONS: These
      results provide evidence that EZH2 function can be counteracted by
      pharmacological inhibition in embryonal RMS blocking proliferation even in a pro
      proliferative context. They also suggest that this approach could be exploited as
      a differentiation therapy in adjuvant therapeutic intervention for embryonal RMS.

PMID- 24575775
TI  - Cardiomyocyte changes in the metabolic syndrome and implications for endogeneous
      protective strategies.
AB  - The deadly quartet of the metabolic syndrome includes obesity, impaired glucose
      tolerance, an atherogenic lipid profile and hypertension. The synergistic effects
      of these comorbidities lead to a combination of functional and structural
      cardiomyocyte changes and finally result in a global adverse remodeling process.
      Overall cardiovascular outcome is significantly impaired. Furthermore, these
      changes increase the need for surgical or endovascular interventions and impair
      their outcomes. This is potentially due to current cardioprotective techniques
      being insufficiently tailored to the specific needs of these patients. The
      following review discusses the observed cardiomyocyte changes and systemic
      factors contributing to these changes. It describes the ensuing problems in
      cardioprotection and discusses strategies that can be taken to divert or
      circumvent these detrimental changes. 

PMID- 24575776
TI  - Myxomatous mitral valve disease bench to bedside: LDL-density-pressure regulates
      Lrp5.
AB  - The myxomatous mitral valve is the most common form of valvular heart disease.
      The pathologic presentation of myxomatous mitral valve disease varies between
      valve thickness, degree of leaflet prolapse and the presence or absence of flail
      leaflets. Recent molecular biology studies have confirmed that the myxomatous
      changes in mitral valve prolapse equals a cartilage phenotype, which is regulated
      by the Lrp5 receptor. Clinically, echocardiography defines the valve pathology to
      determine the surgical approach to valve repair or replacement. Furthermore, the
      timing of surgical valve repair is controversial and is the subject of a current
      multicenter trial. The results will resolve the timing of whether watchful
      waiting versus early surgical valve repair decreases morbidity and mortality of
      this disease process. This review will summarize the current understanding of the
      cellular and hemodynamic mechanisms of myxomatous mitral valve disease, which may
      have future implications in the targeted therapy of this disease process. 

PMID- 24575777
TI  - Effect of induced LV dyssynchrony by right ventricular apical pacing on all-cause
      mortality and heart failure hospitalization rates at long-term follow-up.
AB  - BACKGROUND: Right ventricular apical (RVA) pacing may induce left ventricular
      (LV) dyssynchrony. The long-term prognostic implications of induction of LV
      dyssynchrony were retrospectively evaluated in a cohort of patients who underwent
      RVA pacing. METHODS: A total of 169 patients (62 +/- 13 years, 69% male) with
      high RVA pacing burden were included. Echocardiographic evaluation of LV volumes,
      ejection fraction, and dyssynchrony were performed before and after device
      implantation. LV dyssynchrony was assessed by 2-dimensional radial strain speckle
      tracking echocardiography. Based on the median LV dyssynchrony value after RVA
      pacing, the patient population was dichotomized (induced and noninduced LV
      dyssynchrony groups) and was followed up for the occurrence of all-cause
      mortality and heart failure (HF) hospitalization. RESULTS: Baseline mean LV
      ejection fraction was 51 +/- 11%. Median LV dyssynchrony value was 40 ms (12-85
      ms) before RVA pacing and increased to 91 ms (81-138 ms) after a median of 13
      months (3-26 months) after RVA pacing. Median follow-up duration was 70 months
      (interquartile range 42-96 months). Patients with induced LV dyssynchrony,
      defined as LV dyssynchrony value superior to the median at follow-up (>=91 ms),
      showed higher mortality rates (5% and 27% vs. 1% and 3% at 3 and 5 years follow
      up; log-rank P = 0.003) and HF hospitalization rates (18% and 24% vs. 3% and 4%
      at 3 and 5 years follow-up; log-rank P < 0.001) than patients with LV
      dyssynchrony <91 ms after RVA pacing. A multivariate model was developed to
      identify independent associates of a combined endpoint of all-cause mortality or
      HF hospitalization. Induction of LV dyssynchrony was independently associated
      with increased risk of combined endpoint (HR [95% CI]: 3.369 [1.732-6.553], P <
      0.001). CONCLUSION: Induction of LV dyssynchrony by RVA pacing is associated with
      worse long-term mortality and increased HF hospitalization rates.

PMID- 24575778
TI  - Issues and pitfalls in method comparison studies.
AB  - Method comparison studies are needed for validation of new methods of
      measurements, for example, non-invasive blood pressure measurements against
      standard reference methods. After a brief introduction into method comparison
      studies, this paper is organized in three sections. The first section deals with
      the widely, though not always appropriately, used classical Bland-Altman plot
      with the limits of agreement and its extensions with non-constant bias and
      multiple observations. The second section comments on other statistical
      approaches including correlation coefficients, linear regressions and
      sensitivities and specificities which are sometimes seen in method comparison
      studies. The third section proposes the usage of linear mixed effects models as a
      flexible way to deal with questions associated with method comparison studies. 

PMID- 24575780
TI  - Capabilities of single particle inductively coupled plasma mass spectrometry for
      the size measurement of nanoparticles: a case study on gold nanoparticles.
AB  - The increasing application of engineered nanomaterials (ENMs) in consumer and
      medical products has motivated the development of single-particle inductively
      coupled plasma mass spectrometry (spICP-MS) for characterizing nanoparticles
      under realistic environmental exposure conditions. Recent studies have
      established a set of metrological criteria and evaluated the feasibility of spICP
      MS for sizing or quantifying various highly commercialized ENMs. However, less is
      known about the performance of spICP-MS for detecting nanoparticles with sizes
      greater than 80 nm. This paper presents a systematic study on spICP-MS for
      accurate size measurement of gold nanoparticles from 10 to 200 nm. We show that
      dwell time contributes significantly to the quality of data, with the optimal
      dwell time that limits split particle events, particle coincidences and false
      positives being 10 ms. A simple approach to correct for split particle events is
      demonstrated. We show that transient features of single particle events can be
      temporally resolved on a conventional quadrupole ICP-MS system using a
      sufficiently short dwell time (0.1 ms). We propose an intensity-size diagram for
      estimating the linear dynamic size range and guiding the selection of ICP-MS
      operating conditions. The linear dynamic size range of the ICP-MS system under
      standard (highest) sensitivity conditions is 10 to 70 nm but can be further
      extended to 200 nm by operating in less sensitive modes. Finally, the ability of
      spICP-MS to characterize heterogeneous forms of metal containing nanoparticles is
      evaluated in mixtures containing both dissolved and poly disperse nanoparticulate
      Au. 

PMID- 24575779
TI  - Phenazopyridine associated acute interstitial nephritis and review of literature.
AB  - Phenazopyridine is a urinary analgesic; commonly seen side-effects of this drug
      include, orange discoloration of urine, methemoglobinemia, yellowish skin
      discoloration, hepatitis and acute renal failure. Various case reports with
      phenazopyridine associated acute renal failure secondary to acute tubular
      necrosis have been reported in the literature. Acute kidney injury in these
      patients is caused by either direct injury to renal tubular epithelial cells or
      secondary to pigment induced nephropathy from hemolytic anemia. Hypoxic injury
      from phenazopyridine-induced methemoglobinemia has been well documented. We
      report a case of biopsy proven acute interstitial nephritis, associated with
      therapeutic doses of phenazopyridine without any evidence of methemoglobinemia or
      other mechanism of renal injury. Clinicians should be aware of the toxicity of
      this commonly used drug and should look closely for signs of renal insufficiency.
      Identifying and stopping the offending medication stays as the first step, but
      recent studies indicate that early steroid administration improves renal
      recovery, as well as decreasing the risk of progression to chronic kidney disease
      with fibrosis and consequent permanent renal damage.

PMID- 24575783
TI  - Effect of Number of Graphic Symbols, Levels, and Listening Conditions on Symbol
      Identification and Latency in Persons with Aphasia.
AB  - This study investigated the ability of persons with aphasia to complete a series
      of experimental tasks involving single symbol and subject-verb-object sentence
      identification on a speech-generating device (SGD) in the presence/absence of
      competing stimuli. In all, 10 persons with Broca's aphasia and 10 persons in the
      control group were compared on accuracy and response latency of symbol
      identification across three listening conditions. Persons with aphasia identified
      fewer symbols accurately and had longer response latencies than persons in the
      control group. Number of symbols on the screen and location level had a
      significant effect on accuracy and latency for both groups. Persons with aphasia
      perceived tasks to be more difficult than persons in the control group. Results
      indicate that effective use of SGDs by persons with aphasia may depend on several
      message organization factors including location and number of symbols per screen.

PMID- 24575782
TI  - Pathological Findings in Feto-maternal Hemorrhage.
AB  - Feto-maternal hemorrhage (FMH) is the cause of late fetal death in 1.6%-11% of
      cases. In spite of this high frequency, its pathological features have received
      little attention. The definitive diagnosis of lethal FMH requires confirmation of
      sufficient fetal blood volume loss. This is determined by tests such as the
      Kleihauer-Betke test, which may not have been obtained or not have been available
      before the autopsy. The pathologist may offer a tentative diagnosis of FMH from
      the autopsy findings. The objective of this study was to better characterize the
      placental and fetal autopsy findings in lethal FMH. This was a retrospective
      study of 17 cases of FMH proven by a positive Kleihauer-Betke test. The cases
      were selected from the autopsy files of the Department of Pathology, Centre
      Hospitalier Universitaire de Bordeaux. The pathological reports as well as the
      placental and fetal photographs and the microscopic slides of each case were
      systematically reviewed. The fetal autopsy findings in FMH are characterized by a
      eutrophic pale macerated fetus, low liver weight, absent intrathoracic petechiae,
      increased extramedullary hematopoiesis in the liver and kidney, and increased
      circulating nucleated red blood cells. The placenta shows an increased frequency
      of intervillous thrombi. Although nonpathognomonic, some of the pathological
      features are strongly suggestive of FMH. When the latter is present, a Kleihauer
      Betke test should be performed, even some days after the delivery.

PMID- 24575781
TI  - Evaluation of image registration spatial accuracy using a Bayesian hierarchical
      model.
AB  - To evaluate the utility of automated deformable image registration (DIR)
      algorithms, it is necessary to evaluate both the registration accuracy of the DIR
      algorithm itself, as well as the registration accuracy of the human readers from
      whom the "gold standard" is obtained. We propose a Bayesian hierarchical model to
      evaluate the spatial accuracy of human readers and automatic DIR methods based on
      multiple image registration data generated by human readers and automatic DIR
      methods. To fully account for the locations of landmarks in all images, we treat
      the true locations of landmarks as latent variables and impose a hierarchical
      structure on the magnitude of registration errors observed across image pairs.
      DIR registration errors are modeled using Gaussian processes with reference prior
      densities on prior parameters that determine the associated covariance matrices.
      We develop a Gibbs sampling algorithm to efficiently fit our models to high
      dimensional data, and apply the proposed method to analyze an image dataset
      obtained from a 4D thoracic CT study.

PMID- 24575784
TI  - 100 nanometers: a potentially inappropriate threshold for environmental and
      ecological effects of nanoparticles.

PMID- 24575785
TI  - Formation of trans fatty acids during the frying of chicken fillet in corn oil.
AB  - To assess effects of heated edible oils on intake of trans fatty acids (TFAs);
      the formation of TFAs in cooking conditions was investigated by a frying system
      model, in which chicken fillet was fried in a commercial corn oil at 170  degrees
      C, for 12 frying cycles. The main TFAs detected in chicken fillet were trans
      C18:2 fatty acids (FAs) and trans C18:3 FAs, which exhibited no significant
      differences among the frying cycles. Besides, the content of trans C18:1 FAs were
      very low in all samples on different frying cycles. The intake of TFAs was
      estimated to be 0.06 g/100 g when chicken fillet fried in this process was
      consumed. These results suggest that an ordinary frying process upon a commercial
      corn oil has little impact on the daily TFAs intake.

PMID- 24575787
TI  - A surveillance program on canine leishmaniasis in the public kennels of Emilia
      Romagna Region, Northern Italy.
AB  - Since 2007, a canine leishmaniasis (CanL) surveillance program has been carried
      out in public kennels of the Emilia-Romagna region with the aim of providing
      health guarantees for dog adoptions. According to this program, monitoring
      activities were performed to verify the presence of sandflies and infected dogs,
      and a specific CanL risk class was assigned to each kennel, resulting in
      different control approaches (entomological and/or serological monitoring,
      clinical surveillance, therapeutic treatment of infected dogs, protections
      against vector bites). From 2007 to 2012, 20,931 dogs, 89.8% of which were
      identified by microchip and housed in 73 kennels, were examined using an indirect
      fluorescent antibody test. In all, 528 (2.8%) dogs tested positive, and 43.0% of
      these were asymptomatic. The authors used monitoring results, in particular
      serological tests performed on dogs at admittance to the kennel and annual
      controls of sentinel dogs, to estimate CanL risk in the whole region and to
      evaluate the efficacy of the preventive measures adopted. CanL seroprevalence in
      dogs tested at the admittance in kennels increased significantly from 2010 (1.0%;
      29/2858) to 2012 (2.4%; 69/2841). In contrast, the number of seroconversions in
      sentinel dogs was stable in 2010 (1.2%; 11/896) and 2011 (1.6%; 13/825) and
      decreased in 2012 (0.9%; 8/850), suggesting the efficacy of the preventive
      measures applied.

PMID- 24575788
TI  - The panorama of cerebral palsy in Sweden. XI. Changing patterns in the birth-year
      period 2003-2006.
AB  - AIM: To describe the epidemiology of cerebral palsy (CP) in western Sweden.
      METHODS: A population-based study covering 94 466 live births in the area in 2003
      2006. Birth characteristics and neuroimaging findings were recorded, prevalence
      was calculated and aetiology was analysed. RESULTS: CP was found in 206 children,
      including postneonatal cases, corresponding to a crude prevalence of 2.18 per
      1000 live births. The gestational age-specific prevalence for <28 gestational
      weeks was 71.4 per 1000 live births, while it was 39.6 for 28-31 weeks, 6.4 for
      32-36 weeks and 1.41 per 1000 for >36 weeks. Hemiplegia accounted for 44%,
      diplegia for 29% and tetraplegia for 6%, while 16% had dyskinetic CP and 5% had
      ataxia. Neuroimaging was available in 95% of the children. This showed
      maldevelopment in 13%, white matter lesions in 36%, cortical/subcortical lesions
      in 23% and basal ganglia lesions in 14%. The aetiology was considered to be
      prenatal in 36% and perinatal/neonatal in 46% and remained unclassified in 18%.
      CONCLUSION: The overall prevalence of CP in western Sweden was stable. However,
      the distribution of CP types changed and the term hemiplegia increased
      significantly. Among children with CP born extremely preterm, the percentage born
      before 26 weeks of gestation had increased.

PMID- 24575789
TI  - Biomimetic total synthesis of (+/-)-doitunggarcinone A and (+)-garcibracteatone.
AB  - A full account of our oxidative radical cyclization approach to the synthesis of
      garcibracteatone and doitunggarcinone A is presented. This includes the first
      enantioselective synthesis of garcibracteatone, which allowed the absolute
      configuration of the natural compound to be determined. The first synthesis of
      doitunggarcinone A is also described, which confirms our reassignment of the
      relative configuration of this molecule. Novel syntheses of monoterpene fragments
      used to construct the target molecules are also reported. 

PMID- 24575790
TI  - Prediction of postpartum hemorrhage in women with gestational hypertension or
      mild preeclampsia at term.
AB  - OBJECTIVE: To assess whether postpartum hemorrhage can be predicted in women with
      gestational hypertension or mild preeclampsia at term. DESIGN: A cohort study in
      which we used data from our multicentre randomized controlled trial (HYPITAT
      trial). SETTING: The study was conducted in 38 hospitals in the Netherlands
      between 2005 and 2008. POPULATION: Women with gestational hypertension or mild
      preeclampsia at term (n = 1132). METHODS: An antepartum model (model A) and an
      antepartum/intrapartum model (model B) were created using logistic regression.
      The predictive capacity of the models was assessed with receiver operating
      characteristic analysis and calibration. MAIN OUTCOME MEASURE: Postpartum
      hemorrhage, defined as blood loss >1000 mL within 24 h after delivery. RESULTS:
      Postpartum hemorrhage occurred in 118 (10.4%) women. Maternal age (odds ratio
      1.03), prepregnancy body mass index (odds ratio 0.96), and women with
      preeclampsia (odds ratio 1.5) were independent antepartum prognostic variables of
      postpartum hemorrhage. Intrapartum variables incorporated in the model were
      gestational age at delivery (odds ratio 1.2), duration of dilatation stage (odds
      ratio 1.1), and episiotomy (odds ratio 1.5). Model A and model B showed moderate
      discrimination, with areas under the receiver operating characteristic curve of
      0.59 (95% confidence interval 0.53-0.64) and 0.64 (95% confidence interval 0.59
      0.70), respectively. Calibration was moderate for model A (Hosmer-Lemeshow p =
      0.26) but better for model B (Hosmer-Lemeshow p = 0.36). The rates of postpartum
      hemorrhage ranged from 4% (lowest 10%) to 22% (highest 10%). CONCLUSION: In the
      assessment of performance of a prediction model, calibration is more important
      than discriminative capacity. Our prediction model shows that for women with
      gestational hypertension or mild preeclampsia at term, distinction between low
      and high risk of developing postpartum hemorrhage is possible when antepartum and
      intrapartum variables are combined.

PMID- 24575791
TI  - Mutation screening of the HGD gene identifies a novel alkaptonuria mutation with
      significant founder effect and high prevalence.
AB  - Alkaptonuria (AKU) is an autosomal recessive disorder; caused by the mutations in
      the homogentisate 1, 2-dioxygenase (HGD) gene located on Chromosome 3q13.33. AKU
      is a rare disorder with an incidence of 1: 250,000 to 1: 1,000,000, but Slovakia
      and the Dominican Republic have a relatively higher incidence of 1: 19,000. Our
      study focused on studying the frequency of AKU and identification of HGD gene
      mutations in nomads. HGD gene sequencing was used to identify the mutations in
      alkaptonurics. For the past four years, from subjects suspected to be clinically
      affected, we found 16 positive cases among a randomly selected cohort of 41
      Indian nomads (Narikuravar) settled in the specific area of Tamil Nadu, India.
      HGD gene mutation analysis showed that 11 of these patients carry the same
      homozygous splicing mutation c.87 + 1G > A; in five cases, this mutation was
      found to be heterozygous, while the second AKU-causing mutation was not
      identified in these patients. This result indicates that the founder effect and
      high degree of consanguineous marriages have contributed to AKU among nomads.
      Eleven positive samples were homozygous for a novel mutation c.87 + 1G > A, that
      abolishes an intron 2 donor splice site and most likely causes skipping of exon
      2. The prevalence of AKU observed earlier seems to be highly increased in people
      of nomadic origin.

PMID- 24575793
TI  - Multicenter randomized, open-label phase II trial of sequential erlotinib and
      gemcitabine compared with gemcitabine monotherapy as first-line therapy in
      elderly or ECOG PS two patients with advanced NSCLC.
AB  - AIM: The potential beneficial interaction between erlotinib and chemotherapy may
      require sequencing or pharmacodynamic separation. The aim of this study was to
      evaluate the efficacy and tolerance of sequential erlotinib and gemcitabine
      versus gemcitabine monotherapy as first-line therapy in elderly or ECOG PS-2
      patients with advanced non-small cell lung carcinoma. METHODS: The primary
      objective of this multicenter randomized Phase II study was progression-free
      survival (PFS). Secondary objectives were overall response rate (ORR), disease
      control rate, response duration, overall survival and safety. Patients were
      randomized to either gemcitabine (1250 mg/m2 Day 1, 8 q28 days) followed by
      erlotinib (150 mg/day on day 15 through day 28), (EG-arm), or gemcitabine
      monotherapy (1000 mg/m2 Days 1, 8, 15 q28 days), (G-arm) for up to six cycles.
      RESULTS: Fifty-four patients were recruited, 28 G-arm and 26 EG-arm. Overall,
      efficacy results were not significantly different between study arms. Median PFS
      and ORR for the G- versus EG-arms were 8.0 versus 10.3 weeks (hazard ratio 1.3;
      95% confidence interval [0.63;2.68]; P=0.48) and 7.1 versus 3.8 percent
      respectively (difference -3.30; 95% confidence interval [-17.5;10.9]). The
      majority of adverse events (AEs) in both arms were Grade 1-2. The commonest AEs
      recorded in the EG- and G-arms were rash-like events (65 percent) and nausea (42
      percent) respectively. Four patients (17 percent) in EG-arm and five (16 percent)
      in G-arm experienced at least one treatment-related serious AE. CONCLUSIONS: In
      this study, patients with non-small cell lung carcinoma at ECOG PS-2 or aged >=70
      years derived no efficacy advantage from sequential erlotinib in combination with
      gemcitabine relative to gemcitabine alone. No unexpected safety findings were
      noted.

PMID- 24575794
TI  - Long-term changes in heart rate variability after radiofrequency catheter
      ablation for atrial fibrillation: 1-year follow-up study with irrigation tip
      catheter.
AB  - BACKGROUND: Radiofrequency catheter ablation (RFCA) for atrial fibrillation (AF)
      changes cardiac autonomic nerve activity. However, the long-term effect of RFCA
      has not yet been evaluated when an open irrigation tip catheter (OITC) was used.
      Therefore, we hypothesized that AF ablation changes heart rate variability (HRV)
      that would be maintained over 1 year after OITC ablation and be associated with
      clinical recurrence of AF. METHODS AND RESULTS: We analyzed pre-RFCA HRV (HRVpre
      ), HRV at 3 months (HRV3mo ) and 1 year (HRV1yr ) after RFCA using 24-hour Holter
      monitoring after excluding arrhythmic events in 144 patients (70% male, 57 +/- 10
      years old, 83% paroxysmal AF) who underwent RFCA with OITC. After RFCA with OITC,
      the increase in mean heart rate and the reduction in HF or LF/HF were significant
      at HRV3mo (P < 0.001) and were maintained at HRV1yr (P < 0.001). During 20 +/- 8
      months of follow-up, 33 of 144 patients (23%) showed clinical recurrence of AF.
      Patients in the nonrecurrence group showed significant reductions of rMSSD and HF
      at HRV3mo and HRV1yr , but patients with clinical recurrence did not. In Cox
      regression analysis, a reduction in LF/HF (DeltaLF/HF) >=0.26 at HRV3mo was
      significantly associated with clinical recurrence of AF (hazard ratio 2.52, 95%
      CI 1.19-5.32, P = 0.015). CONCLUSION: In contrast to previous reports about long
      term HRV recovery after AF ablation with a conventional catheter, change in
      cardiac autonomic nervous activity was maintained for 1 year after RFCA when an
      OITC was used. A reduction in DeltaLF/HF >=0.26 at HRV3mo was independently
      associated with clinical recurrence of AF after RFCA.

PMID- 24575795
TI  - Cyclopropene cycloadditions with annulated furans: total synthesis of (+)- and (
      )-frondosin B and (+)-frondosin A.
AB  - The asymmetric total syntheses of the natural products (+)- and (-)-frondosin B
      and (+)-frondosin A are reported based on a diastereoselective cycloaddition
      between tetrabromocyclopropene and an annulated furan to provide a highly
      functionalized common building block. The bridged bicyclic intermediate could be
      stereo- and chemoselectively manipulated to produce the two structurally distinct
      members of the frondosins. Both syntheses feature regioselective palladium
      coupling reactions and an unprecedented phosphine-mediated ether bridge cleavage.
      Surprisingly, the planned enantioselective synthesis of frondosin B led to the
      opposite epimer of the natural product, suggesting an unusual late stage
      stereoinversion at C8. Frondosin A, but not frondosin B, was shown to have
      selective antiproliferative activity against several B-cell lines. 

PMID- 24575796
TI  - Exploring patterns of accelerometry-assessed physical activity in elderly people.
AB  - BACKGROUND: Elderly people obtain significant health benefits from physical
      activity (PA), but the role of activity patterns has scarcely been researched.
      The present study aims to describe the patterns of PA among different intensities
      of activity in elderly people. We assess how patterns differ between more and
      less active groups ('rare', 'average', and 'frequent'), and explore whether and
      how various PA parameters are associated with functional exercise capacity (FEC).
      METHODS: PA was measured in 168 subjects (78 males; 65-89 years of age), using a
      triaxial GT3X accelerometer for ten consecutive days. Subjects were divided into
      three groups by activity and the groups were compared. A multiple linear
      regression model was used to predict FEC. RESULTS: Participants greater than or
      equal to 80 years are most prone to being sedentary for long periods, while women
      and the obese are the groups most likely to spend insufficient time in moderate
      to vigorous PA (MVPA). Rarely active elderly people had a decreased proportion of
      long bouts of MVPA and light PA and of short bouts in sedentary behavior than
      frequently active subjects did (p<0.001). As predictors of FEC, younger age,
      lower BMI, male sex, better lung function, absence of multimorbidity, longer
      times and longer bouts of MVPA emerged as significant parameters (r(2)=0.54).
      Patterns of MVPA explained most of the variance. CONCLUSIONS: PA patterns provide
      information beyond reports of activity alone. MVPA in elderly people may be
      increased by increasing the proportion of long bouts, in order to increase FEC as
      well as average PA. However, health conditions may limit PA. In rarely active
      people (often with reduced FEC, worse lung function, and diagnosis of
      multimorbidity or disability), longer periods of time in light PA may be
      sufficient to increase the overall level of activity.

PMID- 24575797
TI  - Minimum infusion rate of alfaxalone for total intravenous anaesthesia after
      sedation with acepromazine or medetomidine in cats undergoing ovariohysterectomy.
AB  - OBJECTIVE: To determine the induction doses, then minimum infusion rates of
      alfaxalone for total intravenous anaesthesia (TIVA), and subsequent,
      cardiopulmonary effects, recovery characteristics and alfaxalone plasma
      concentrations in cats undergoing ovariohysterectomy after premedication with
      butorphanol-acepromazine or butorphanol-medetomidine. STUDY DESIGN: Prospective
      randomized blinded clinical study. ANIMALS: Twenty-eight healthy cats. METHODS:
      Cats undergoing ovariohysterectomy were assigned into two groups: together with
      butorphanol [0.2 mg kg(-1) intramuscularly (IM)], group AA (n = 14) received
      acepromazine (0.1 mg kg(-1) IM) and group MA (n = 14) medetomidine (20 MUg kg(-1)
      IM). Anaesthesia was induced with alfaxalone to effect [0.2 mg kg(-1)
      intravenously (IV) every 20 seconds], initially maintained with 8 mg kg(-1) 
      hour(-1) alfaxalone IV and infusion adjusted (+/-0.5 mg kg(-1)  hour(-1) ) every
      five  minutes according to alterations in heart rate (HR), respiratory rate (fR
      ), Doppler blood pressure (DBP) and presence of palpebral reflex. Additional
      alfaxalone boli were administered IV if cats moved/swallowed (0.5 mg kg(-1) ) or
      if fR >40 breaths minute(-1) (0.25 mg kg(-1) ). Venous blood samples were
      obtained to determine plasma alfaxalone concentrations. Meloxicam (0.2 mg kg(-1)
      IV) was administered postoperatively. Data were analysed using linear mixed
      models, Chi-squared, Fishers exact and t-tests. RESULTS: Alfaxalone anaesthesia
      induction dose (mean +/- SD), was lower in group MA (1.87 +/- 0.5; group AA: 2.57
      +/- 0.41 mg kg(-1) ). No cats became apnoeic. Intraoperative bolus requirements
      and TIVA rates (group AA: 11.62 +/- 1.37, group MA: 10.76 +/- 0.96 mg kg(-1) 
      hour(-1) ) did not differ significantly between groups. Plasma concentrations
      ranged between 0.69 and 10.76 MUg mL(-1) . In group MA, fR , end-tidal carbon
      dioxide, temperature and DBP were significantly higher and HR lower. CONCLUSION
      AND CLINICAL RELEVANCE: Alfaxalone TIVA in cats after medetomidine or
      acepromazine sedation provided suitable anaesthesia with no need for ventilatory
      support. After these premedications, the authors recommend initial alfaxalone
      TIVA rates of 10 mg kg(-1)  hour(-1) .

PMID- 24575798
TI  - Visceral cat scratch disease with endocarditis in an immunocompetent adult: a
      case report and review of the literature.
AB  - Infective endocarditis and hepatosplenic abscesses are rare manifestations of cat
      scratch disease (CSD), especially among immunocompetent adults. An otherwise
      healthy woman who presented with fever and abdominal pain was diagnosed with
      multiple abscesses in the spleen and the liver, as well as a mitral valve
      vegetation. PCR on spleen tissue was positive for Bartonella henselae. Prolonged
      treatment with doxycycline and gentamicin led to complete recovery. Review of the
      literature revealed 18 cases of hepatosplenic CSD in immunocompetent adults; the
      majority presented with fever of unknown origin and abdominal pain. In most cases
      the causative organism was B. henselae and the pathological findings were
      necrotizing granulomas, similar to the pathological features in classic CSD.
      Concomitant endocarditis was diagnosed in one case. Because Bartonella is one of
      the leading pathogens of culture-negative endocarditis, we raise the question of
      whether a comprehensive evaluation for endocarditis is needed in cases of
      systemic CSD.

PMID- 24575799
TI  - Emerging technologies in extracellular vesicle-based molecular diagnostics.
AB  - Extracellular vesicles (EVs), including exosomes and microvesicles, have been
      shown to carry a variety of biomacromolecules including mRNA, microRNA and other
      non-coding RNAs. Within the past 5 years, EVs have emerged as a promising
      minimally invasive novel source of material for molecular diagnostics. Although
      EVs can be easily identified and collected from biological fluids, further
      research and proper validation is needed in order for them to be useful in the
      clinical setting. In addition, innovative and more efficient means of nucleic
      acid profiling are needed to facilitate investigations into the cellular and
      molecular mechanisms of EV function and to establish their potential as useful
      clinical biomarkers and therapeutic tools. In this article, we provide an
      overview of recent technological improvements in both upstream EV isolation and
      downstream analytical technologies, including digital PCR and next generation
      sequencing, highlighting future prospects for EV-based molecular diagnostics. 

PMID- 24575800
TI  - Direct determination of dissolved phosphate and silicate in seawater by ion
      exclusion chromatography sector field inductively coupled plasma mass
      spectrometry.
AB  - A method is described for the direct determination of dissolved phosphate and
      silicate in seawater using ion exclusion chromatography (IEC) coupled with sector
      field inductively coupled plasma mass spectrometry (SF-ICPMS). Dissolved silicate
      was determined by double isotope dilution using a (29)Si spike, whereas one point
      gravimetric standard addition with internal standard of the same (29)Si spike was
      employed to quantitate dissolved phosphate. Medium resolution was used for all
      measurements in order to resolve polyatomic interferences on Si and P isotopes.
      Concentrations of 1.670 +/- 0.008 and 30.20 +/- 0.09 MUM (SD, n = 6) with
      precisions of 0.47 and 0.31% for the dissolved phosphate and silicate,
      respectively, were obtained in National Research Council Canada certified
      reference material MOOS-3 seawater, in good agreement with certified values of
      1.60 +/- 0.15 and 30.5 +/- 0.8 MUM (U, k = 2), respectively. The reported method
      is a rapid (10 min per run), simple, and accurate online technique that requires
      no sample pretreatment. Moreover, this procedure achieves <0.5% precision (at
      above analyte concentrations) and method detection limits of 0.006 and 0.004 MUM
      (0.18 as P and 0.11 ng g(-1) as Si), respectively, using a of 100 MUL injection
      of seawater. The proposed technique is robust and well-suited for the
      determination of dissolved phosphate and silicate in seawater. 

PMID- 24575801
TI  - Comparison of radiographic femur measurements in stillbirths and neonatal deaths
      to ultrasound measurements in ongoing pregnancies.
AB  - Identifying growth abnormalities in stillbirths is clinically useful but
      complicated by maceration. This is an observational study of consecutive
      postmortem examinations in which femur lengths and gestational age at delivery
      were collected, along with associated congenital anomalies and extent of fetal
      maceration. Between 2005 and 2012, 1530 consecutive postmortem examinations were
      performed and the information recorded. Fragmented fetuses (417), live-born
      fetuses that survived for more than 24 hours (134), fetuses with any signs of
      maceration (419), fetuses with known anomalies (98), and records with missing
      data (249) were excluded. The analyses focused on the remaining 265 nonmacerated
      stillborn fetuses and infants that survived for less than 24 hours after birth.
      The relationship between gestational age at delivery and femur length was
      computed, and a quadratic equation fit the data well between 12 and 40 weeks'
      gestation (R  =  0.944). Gestational age-specific reference ranges for
      radiographic femur measurements in stillbirths are equivalent to those for
      ultrasound-determined measurements in ongoing pregnancies. These reference data
      may be useful in identifying growth abnormalities in nonmacerated stillborn
      fetuses.

PMID- 24575802
TI  - Trainee resident participation in health research in a resource-constrained
      setting in south-eastern Nigeria: perspectives, issues and challenges. A cross
      sectional survey of three residency training centres.
AB  - BACKGROUND: The participation of trainers and trainees in health research is
      critical to advance medical science. Overcoming barriers and enhancing incentives
      are essential to sustain a research culture and extend the frontiers of medical
      education. In this study, we investigated the roles of individual and system
      factors influencing trainee resident participation in health research in Enugu,
      south-eastern Nigeria. METHODS: This cross-sectional survey of trainee residents
      was conducted across three residency training centres in Enugu, Nigeria, between
      February and March, 2010. The number and speciality distribution of trainee
      residents were determined from personnel records at each centre. A 19-item
      questionnaire was used to record demographic characteristics, research
      training/experience, and attitudes toward and perceived barriers to health
      research. Data were analysed to yield frequencies, percentages and proportions.
      Values of p<0.05 were considered significant. RESULTS: The response rate was
      93.2%. The respondents (n=136) comprised 109 males and 27 females. Their mean+/
      standard deviation age was 35.8+/-5.6 years (range: 25-53 years). Participation
      in research was significantly associated with previous research training [odds
      ratio (OR): 2.90; 95% confidence interval (CI): 1.35-6.25, p=0.003, beta=22.57],
      previous research participation (OR: 2.21; 95% CI: 0.94-5.29, p=0.047,
      beta=22.53) and research publication (OR: 2.63; 95% CI: 1.00-7.06, p=0.03,
      beta=22.57). Attitude towards research was significantly influenced by perceived
      usefulness of research in patient care (OR: 7.10; 95% CI: 3.33-15.13, p=0.001),
      job promotion (OR: 8.97; 95% CI: 4.12-19.53, p=0.001) and better understanding of
      disease (OR: 21.37; 95% CI: 8.71-54.44, p=0.001). Time constraints (OR: 0.06; 95%
      CI=0.025-0.14, p=0.001), funding (OR: 0.028; 95% CI: 0.008-0.10, p=0.001) and
      mentorship (OR: 0.086; 95% CI: 0.36-0.21, p=0.001) were significant barriers to
      research participation. CONCLUSIONS: System and individual factors are
      significant incentives to research participation, while system-derived factors
      are significant barriers. Pre-residency research, dedicated research time,
      adequate research funding and commensurate research mentorship rewards are
      instructive. Prospective longitudinal studies are warranted to confirm these
      findings.

PMID- 24575803
TI  - Are we really closer to improving the diagnostic sensitivity in ALS patients with
      Awaji criteria?
AB  - The Awaji criteria, recently introduced to increase diagnosis sensitivity in
      amyotrophic lateral sclerosis (ALS), equate the diagnostic significance of
      neurogenic electrophysiological changes to clinical signs of lower motor neuron
      dysfunction. They also increase the electrophysiological significance of
      fasciculation potentials (FPs). The aim of our study was to analyse whether the
      new parameters improve diagnostic sensitivity in ALS patients primarily diagnosed
      with the El Escorial criteria. Medical and electrophysiological records of 135
      consecutive patients with ALS and 25 patients with progressive muscular atrophy
      (PMA) who underwent electrophysiological examination of at least three anatomical
      regions were analysed retrospectively. Results showed that implementation of the
      Awaji criteria increased the level of ALS diagnosis sensitivity in 5.9% of cases 
      1.5% due to the new role of FPs potentials and 4.4% because of equalization of
      clinical and EMG findings. In 4% of patients the ALS diagnosis was, however,
      changed from laboratory-supported probable ALS to possible ALS. In conclusion,
      our study confirms that Awaji modifications are able to improve the diagnostic
      certainty in a few ALS cases. Although the new approach to FPs markedly increases
      the number of involved muscles, it only slightly raises the number of involved
      regions.

PMID- 24575805
TI  - Women's antenatal preferences for delivery route in a setting with high cesarean
      section rates and a medically dominated maternity system.
AB  - OBJECTIVE: To assess birth preferences in a sample of Hungarian pregnant women
      and identify determinants of ambivalence or clear choices for cesarean section
      throughout pregnancy. DESIGN: Follow-up two-point questionnaire survey. SETTING:
      University Department of Obstetrics and Gynecology in Hungary. SAMPLE: A total of
      413 women with singleton pregnancies where there was no awareness of medical
      contradictions to vaginal delivery, attending for routine ultrasound examination
      in mid-pregnancy from November 2011 to March 2012. METHODS: Questionnaires
      completed in mid- and late pregnancy (gestational weeks 18-22 and 35-37)
      including the Wijma Delivery Expectancy/Experience Questionnaire A. MAIN OUTCOME
      MEASURES: Prevalence of women preferring cesarean section or being uncertain
      about what delivery route to choose, in case they had the choice; their
      demographic characteristics, attitudes toward birth issues and their Wijma
      Delivery Expectancy/Experience Questionnaire A scores, compared with women
      consistent in their preference for vaginal delivery. RESULTS: Of the 413
      respondents, 365 (88.4%) were consistent in their preference for vaginal
      delivery. In logistic regression models the important contributors to describing
      preferences for cesarean section or uncertain preferences were previous cesarean
      section and maternal belief that cesarean section is more beneficial than vaginal
      delivery. CONCLUSIONS: The majority of pregnant women preferred vaginal delivery
      to cesarean section. Neither a higher Wijma Delivery Expectancy/Experience
      Questionnaire A score nor sociodemographic differences were important
      determinants of a preference for cesarean section or for an uncertain preference.
      On the other hand, previous cesarean section and certain preconceived maternal
      attitudes towards delivery were characteristic for these women.

PMID- 24575804
TI  - Age-related differences in advantageous decision making are associated with
      distinct differences in functional community structure.
AB  - Human decision making is dependent on not only the function of several brain
      regions but also their synergistic interaction. The specific function of brain
      areas within the ventromedial prefrontal cortex has long been studied in an
      effort to understand choice evaluation and decision making. These data
      specifically focus on whole-brain functional interconnectivity using the
      principles of network science. The Iowa Gambling Task (IGT) was the first
      neuropsychological task used to model real-life decisions in a way that factors
      reward, punishment, and uncertainty. Clinically, it has been used to detect
      decision-making impairments characteristic of patients with prefrontal cortex
      lesions. Here, we used performance on repeated blocks of the IGT as a behavioral
      measure of advantageous and disadvantageous decision making in young and mature
      adults. Both adult groups performed poorly by predominately making
      disadvantageous selections in the beginning stages of the task. In later phases
      of the task, young adults shifted to more advantageous selections and
      outperformed mature adults. Modularity analysis revealed stark underlying
      differences in visual, sensorimotor and medial prefrontal cortex community
      structure. In addition, changes in orbitofrontal cortex connectivity predicted
      behavioral deficits in IGT performance. Contrasts were driven by a difference in
      age but may also prove relevant to neuropsychiatric disorders associated with
      poor decision making, including the vulnerability to alcohol and/or drug
      addiction.

PMID- 24575807
TI  - Association of megsin 2093C/T, 2180C/T and C25663G gene polymorphism with the
      risk of IgA nephropathy.
AB  - The association between megsin 2093C/T, 2180C/T and C25663G gene polymorphisms
      and IgA nephropathy (IgAN) risk remains unclear. We aimed to evaluate the
      association between megsin 2093C/T, 2180C/T and C25663G gene polymorphisms and
      IgAN risk by performing a meta-analysis. Eligible studies were searched according
      to predefined criteria by using electronic databases. Six articles were
      identified for the analysis of the association between megsin 2093C/T, 2180C/T
      and C25663G gene polymorphisms and IgAN risk. 2093C/T C allele was associated
      with IgAN risk in overall populations and Asians (overall populations: p = 0.014,
      Asians: p = 0.037). 2093C/T CC/TT genotype was not associated with IgAN risk in
      overall populations, Caucasians and Asians. 2180C/T C allele was correlated with
      IgAN risk in Caucasians (p = 0.024). 2180C/T CC/TT genotype was not associated
      with IgAN risk in overall populations, Caucasians and Asians. C25663G gene
      polymorphism was not associated with IgAN onset in Asians. In conclusion, megsin
      2093C/T C allele may be genetic marker for IgAN susceptibility in overall
      populations and Asians. 2180C/T C allele may be risk factor for IgAN onset in
      Caucasians. However, more studies should be performed in the future.

PMID- 24575806
TI  - Extensive protein hydrolysate formula effectively reduces regurgitation in
      infants with positive and negative challenge tests for cow's milk allergy.
AB  - AIM: Cow's milk protein allergy (CMPA) is treated using an elimination diet with
      an extensive protein hydrolysate. We explored whether a thickened or nonthickened
      version was best for infants with suspected CMPA, which commonly causes
      regurgitation/vomiting. METHODS: Diagnosis of CMPA was based on a positive
      challenge test. We compared the efficacy of two casein extensive hydrolysates
      (eCH), a nonthickened version (NT-eCH) and a thickened version (T-eCH), using a
      symptom-based score covering regurgitation, crying, stool consistency, eczema,
      urticarial and respiratory symptoms. RESULTS: A challenge was performed in 52/72
      infants with suspected CMPA and was positive in 65.4%. All confirmed CMPA cases
      tolerated eCH. The symptom-based score decreased significantly in all infants
      within a month, and the highest reduction was in those with confirmed CMPA.
      Regurgitation was reduced in all infants (6.4 +/- 3.2-2.8 +/- 2.9, p < 0.001),
      but fell more with the T-eCH (-4.2 +/- 3.2 regurgitations/day vs. -3.0 +/- 4.5,
      ns), especially in infants with a negative challenge (-3.9 +/- 4.0 vs. -1.9 +/-
      3.4, ns). CONCLUSION: eCH fulfilled the criteria for a hypoallergenic formula,
      and the NT-eCH and T-eCH formulas both reduced CMPA symptoms. The symptom-based
      score is useful for evaluating how effective dietary treatments are for CMPA.

PMID- 24575808
TI  - Diffusible signal factor (DSF) quorum sensing signal and structurally related
      molecules enhance the antimicrobial efficacy of antibiotics against some
      bacterial pathogens.
AB  - BACKGROUND: Extensive use of antibiotics has fostered the emergence of superbugs
      that are resistant to multidrugs, which becomes a great healthcare and public
      concern. Previous studies showed that quorum sensing signal DSF (diffusible
      signal factor) not only modulates bacterial antibiotic resistance through
      intraspecies signaling, but also affects bacterial antibiotic tolerance through
      interspecies communication. These findings motivate us to exploit the possibility
      of using DSF and its structurally related molecules as adjuvants to influence
      antibiotic susceptibility of bacterial pathogens. RESULTS: In this study, we have
      demonstrated that DSF signal and its structurally related molecules could be used
      to induce bacterial antibiotic susceptibility. Exogenous addition of DSF signal
      (cis-11-methyl-2-dodecenoic acid) and its structural analogues could
      significantly increase the antibiotic susceptibility of Bacillus cereus, possibly
      through reducing drug-resistant activity, biofilm formation and bacterial
      fitness. The synergistic effect of DSF and its structurally related molecules
      with antibiotics on B. cereus is dosage-dependent. Combination of DSF with
      gentamicin showed an obviously synergistic effect on B. cereus pathogenicity in
      an in vitro model. We also found that DSF could increase the antibiotic
      susceptibility of other bacterial species, including Bacillus thuringiensis,
      Staphylococcus aureus, Mycobacterium smegmatis, Neisseria subflava and
      Pseudomonas aeruginosa. CONCLUSION: The results indicate a promising potential of
      using DSF and its structurally related molecules as novel adjuvants to
      conventional antibiotics for treatment of infectious diseases caused by bacterial
      pathogens.

PMID- 24575809
TI  - Application of rapid microbiological methods for the risk assessment of
      controlled biopharmaceutical environments.
AB  - AIMS: To assess the different operational states within a biopharmaceutical grade
      clean room, using a rapid microbiological method. The method was a novel system,
      based on spectrometry, designed for sampling, discriminating, and enumerating
      airborne particles. Central to the study was the aim to determine the
      microbiological levels as a clean room went from standard use through maintenance
      and shutdown, disinfection, and then back to standard use. The objective was to
      evaluate whether a rapid method could replace conventional environmental
      monitoring using growth-based media. METHODS AND RESULTS: The instrument
      evacuated was a BioVigilant IMD-A((r)) System, which is a real-time and
      continuous monitoring technology based on optical spectroscopy that can
      differentiate between biological particles and inert ones (biological particles
      expressed as bio-counts based on the detection of microbial metabolites). The
      results indicated that certain activities lead to a high generation of biological
      particles and in showing an increase over the baseline, would be regarded as
      presenting a microbiological risk to the cleanroom. These activities include
      removing HEPA filter grilles, turning off an air handing unit, and tasks which
      requires an active personnel presence, such as cleaning and disinfection.
      CONCLUSIONS: The optical instrument can be used to process sufficient
      information, so that clean rooms can be returned to use following a period of
      unexpected downtime or following maintenance without the need to wait for the
      results from growth-based methods. As such, this type of rapid microbiological
      method is worth exploring further for clean room air monitoring. SIGNIFICANCE AND
      IMPACT OF THE STUDY: Few studies have been undertaken which examine air
      monitoring devices that can both enumerate and discriminate particulates, in a
      volume of air as 'inert' or 'biological'. This study extends this limited field.
      Furthermore, the data collected in relation to cleanrooms is of interest in
      helping microbiologists understand that risks posed by different activities in
      relation to clean air-handling systems and personnel particle shedding.

PMID- 24575811
TI  - Role of IGF1 and IGF1/VEGF on human mesenchymal stromal cells in bone healing:
      two sources and two fates.
AB  - In the repair of skeletal defects one of the major obstacles still remains an
      efficient vascularization of engineered scaffolds. We have examined the ability
      of insulin growth factor-1, alone or in association with vascular endothelial
      growth factor, to modulate the osteoblastic or endothelial commitment of
      periosteum-derived progenitor cells (PDPCs) and skin-derived multipotent stromal
      cells (S-MSCs). A selected gene panel for endothelial and osteoblastic
      differentiation as well as genes that can affect MAPK and PI3K/AKT signaling
      pathways were investigated. Moreover, gene expression profile of Sox2, Oct4, and
      Nanog transcription factors was assessed. Our results showed that under growth
      factor stimulation PDPCs are induced toward an osteoblastic differentiation,
      while S-MSCs seem to move along an endothelial phenotype. This different
      commitment seems to be linked to a diverse MAPK or PI3K/AKT signaling pathway
      activation. The analysis of genes for stemness evidenced that at least in PDPCs
      multipotency and differentiation could coexist. These results open interesting
      perspective for the development of innovative bone tissue engineering approaches
      based on a good network of angiogenesis and osteogenesis processes. 

PMID- 24575810
TI  - Analysis of the impact of platinum-based combination chemotherapy in small cell
      cervical carcinoma: a multicenter retrospective study in Chinese patients.
AB  - BACKGROUND: Small cell cervical carcinoma (SCCC) is a rare, aggressive tumor with
      a poor prognosis. However, information in relation to its treatment is scarce due
      to the limited numbers of patients. The aim of this study was to establish
      whether platinum-based combination chemotherapy may by beneficial in this patient
      population. METHODS: We carried out a multicenter, retrospective study comprising
      of 72 Chinese patients with SCCC. The patients were treated between 1995 and 2010
      at Sun Yat-sen Memorial Hospital or the Cancer Center of Sun Yat-Sen University,
      and at the First Affiliated Hospital of Shantou University Medical College,
      China. RESULTS: Of the 72 patients, 46/72 (63.9%) had Federation of Gynecology
      and Obstetrics (FIGO) stage Ia-Ib2 and 26/72 (36.1%) had stage IIa-IV disease.
      Surgery was performed in 63/72 (87.5%) patients, 61/72 (84.7%) patients received
      chemoradiotherapy and 35/72 (48.6%) received radiotherapy. The 3-year overall
      survival (OS) and disease-free survival (DFS) rates were as follows: Ia (100%,
      100%); Ib1 (62%, 57%); Ib2 (53%, 48%); IIa (36%, 23%); IIb (29%, 21%); IIIb (50%,
      50%); and IV (0%, 0%), respectively. The estimated 3-year OS and DFS rates in
      patients who received platinum-based combination chemotherapy (etoposide +
      cisplatin [EP], or paclitaxel + cisplatin [TP]) as part of their adjuvant
      treatment were 64.8% and 63.0%, respectively, compared to 25.2% and 22.0% in
      those who did not (P = 0.0003; P = 0.0003). Univariate analysis showed that
      platinum-based combination chemotherapy was associated with improved survival
      compared to other chemotherapy techniques or no chemotherapy (OS: HR = 0.227; 95%
      CI, 0.099-0.524; P = 0.001; DFS: HR = 0.210; 95% CI, 0.087-0.506; P = 0.001).
      Multivariate analysis identified FIGO stage, lymphatic metastasis and platinum
      based combination chemotherapy as independent prognostic factors for improved
      survival in patients with SCCC. CONCLUSIONS: Platinum-based combination
      chemotherapy (with EP or TP) can improve the 3-year survival outcomes in patients
      with SCCC. Therefore, it should be considered an important component in a future
      standardized treatment strategy for SCCC.

PMID- 24575812
TI  - Is lipoatrophia semicircularis a rare disease? Report of three cases.
AB  - Lipoatrophia semicircularis is characterised by band-like horizontal skin
      depressions involving the anterior and lateral sides of the lower limbs. Whether
      this occurrence is rare or is just not well known or simply underreported because
      it does not cause patient distress is still under discussion. In a 1-year period
      we observed three cases due to local, mechanical pressure in an Italian
      dermatology outpatient clinic. However, other factors described in current
      literature may contribute to this phenomenon. More large-scale studies are needed
      to clearly assess the origin of this condition. 

PMID- 24575813
TI  - Natural killer cells as effectors of selection and differentiation of stem cells:
      role in resolution of inflammation.
AB  - Evidence has previously been demonstrated for the role of NK cells in specific
      elimination of healthy stem cells (e.g. hMSC, hDPSC, hESC, hiPSC) as well as
      cancer stem cells, but not their differentiated counterparts. There is also a
      stage-wise susceptibility to NK cell-mediated cyto-toxicity in tumors, in which
      case the poorly-differentiated tumors are lysed much more than moderately
      differentiated tumors. Well-differentiated tumors were lysed the least compared
      to either moderately- or poorly-differentiated tumors. It has also been reported
      that inhibition of differentiation or reversion of cells to a less-differentiated
      stage by blocking NF-kappaB or by gene deletion of COX2 significantly augmented
      NK cell cytotoxicity against both transformed and healthy cells. Additionally,
      the cytotoxic function of NK cells was severely inhibited against stem cells when
      they were cultured in the presence of monocytes. Therefore, it is proposed that
      CD16(+)CD56(dim)CD69(-) NK cells were important for the selection of stem cells,
      whereas the CD16(dim/-)CD56(dim/+)CD69(+) anergized NK cells were important for
      differentiation and eventual regeneration of the tissues and the resolution of
      inflammation, thus potentially serving as regulatory NK (NK(reg)) cells. The
      concept of 'split anergy' in NK cells and the generation of NK(reg) cells with
      regard to contributions to cell differentiation, tissue repair and regeneration
      and in tumor resistance are discussed in this review.

PMID- 24575814
TI  - Rose Bengal suppresses gastric cancer cell proliferation via apoptosis and
      inhibits nitric oxide formation in macrophages.
AB  - Rose Bengal (RB) has been used as a safe agent in clinical diagnosis. In
      addition, it is used as a photodynamic sensitizer for removing microorganisms and
      cancer cells. Recently, its preferential toxicity after direct exposure to cancer
      cells was proven. The present study focuses on anti-cancer and anti-inflammatory
      activities of RB. The toxicity of RB against AGS gastric cancer and NIH 3T3
      fibroblast cell lines was studied using an MTT assay. Patterns of any cell death
      among the AGS cells were defined using Annexin-V and PI staining. In addition,
      the effect of RB on nitric oxide (NO) and prostaglandin E(2) (PGE(2)) production
      induced by lipopolysaccha-ride in J774A.1 macrophages was determined. Modulation
      of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 expressions
      in the macrophages was also evaluated by Western blots. The results showed that
      AGS cells exhibited significant concentration-dependent decreases in growth in
      response to RB; these cells showed a greater growth inhibition than did non
      malignant 3T3 cells, suggesting that anti-growth activity of RB could be cell
      specific. Moreover, AGS cells exposed to RB exhibited a significant increase in
      apoptosis; only at high RB doses did the cells display significant levels of
      necrosis. While RB also caused a modest decrease in the growth of J774A.1
      macrophages, the cells displayed remarkable decreases in NO production and iNOS
      expression without significant concurrent modulation in PGE(2) production or COX
      2 expression. The data from this study appears to suggest that RB differentially
      impacts on transformed cell lines, preferentially suppresses growth of a gastric
      cancer cell line through induction of apoptosis, and induces changes in cells
      that could reflect potential anti-inflammatory effects that might be induced in
      situ.

PMID- 24575815
TI  - Leishmania braziliensis amastigotes stimulate production of IL-1beta, IL-6, IL-10
      and TGF-beta by peripheral blood mononuclear cells from nonendemic area healthy
      residents.
AB  - Leishmania (Viannia) braziliensis causes cutaneous and mucosal leishmaniasis in
      several countries in Latin America. In mammals, the parasites live as
      amastigotes, interacting with host immune cells and stimulating cytokine
      production that will drive the type of the specific immune responses. Generation
      of Th17 lymphocytes is associated with tissue destruction and depends on IL
      1beta, IL-6, TGF-beta and IL-23 production, whereas IL-10 and TGF-beta are
      associated with tissue protection. Here, we evaluate whether amastigotes
      stimulate peripheral blood mononuclear cells (PBMCs) from healthy donors to
      produce the major cytokines responsible for the generation of Th17. Seven L. (V.)
      braziliensis isolates from patients with different clinical forms of
      leishmaniasis were expanded in interferon-gamma knockout mice to obtain
      amastigotes and in culture to get promastigotes. The parasites were used to
      stimulate PBMCs from healthy donors, and cytokine production was evaluated by
      ELISA or qPCR. Amastigotes and promastigotes induced IL-10 production in PBMCs;
      however, only amastigotes induced IL-1beta, IL-6 and TGF-beta. These data
      demonstrate for the first time that L. (V.) braziliensis amastigotes directly
      stimulate production of a unique pattern of cytokines that could contribute to
      the generation of Th17. 

PMID- 24575816
TI  - Effect of stimulation by foliage plant display images on prefrontal cortex
      activity: a comparison with stimulation using actual foliage plants.
AB  - BACKGROUND AND PURPOSE: Natural scenes like forests and flowers evoke
      neurophysiological responses that can suppress anxiety and relieve stress. We
      examined whether images of natural objects can elicit neural responses similar to
      those evoked by real objects by comparing the activation of the prefrontal cortex
      during presentation of real foliage plants with a projected image of the same
      foliage plants. METHODS: Oxy-hemoglobin concentrations in the prefrontal cortex
      were measured using time-resolved near-infrared spectroscopy while the subjects
      viewed the real plants or a projected image of the same plants. RESULTS: Compared
      with a projected image of foliage plants, viewing the actual foliage plants
      significantly increased oxy-hemoglobin concentrations in the prefrontal cortex.
      However, using the modified semantic differential method, subjective emotional
      response ratings ("comfortable vs. uncomfortable" and "relaxed vs. awakening")
      were similar for both stimuli. CONCLUSIONS: The frontal cortex responded
      differently to presentation of actual plants compared with images of these plants
      even when the subjective emotional response was similar. These results may help
      explain the physical and mental health benefits of urban, domestic, and workplace
      foliage.

PMID- 24575817
TI  - Elucidation of final steps of the marineosins biosynthetic pathway through
      identification and characterization of the corresponding gene cluster.
AB  - The marine Streptomyces sp. CNQ-617 produces two diastereomers, marineosins A and
      B. These are structurally related to alkyl prodiginines, but with a more complex
      cyclization and an unusual spiroaminal skeleton. We report the identification of
      the mar biosynthetic gene cluster and demonstrate production of marineosins
      through heterologous expression in a S. venezuelae host named JND2. The mar
      cluster shares the same gene organization and has high homology to the genes of
      the red cluster (which directs the biosynthesis of undecylprodiginine) but
      contains an additional gene, named marA. Replacement of marA in the JND2 strain
      leads to the accumulation of premarineosin, which is identical to marineosin with
      the exception that the middle pyrrole (Ring B) has not been reduced. The final
      step of the marineosin pathway is thus a MarA catalyzed reduction of this ring.
      Replacement of marG (a homologue of redG that directs undecylprodiginine
      cyclization to give streptorubin B) in the JND2 strain leads to the loss of all
      spiroaminal products and the accumulation of 23-hydroxyundecylprodiginine and a
      shunt product, 23-ketoundecylprodiginine. MarG thus catalyzes the penultimate
      step of the marineosin pathway catalyzing conversion of 23
      hydroxyundecylprodiginine to premarineosin. The preceding steps of the
      biosynthetic marineosin pathway likely mirror that in the red-directed
      biosynthetic process, with the exception of the introduction of the hydroxyl
      functionality required for spiroaminal formation. This work presents the first
      experimentally supported scheme for biosynthesis of marineosin and provides a new
      biologically active molecule, premarineosin. 

PMID- 24575818
TI  - Editorial. Themed issue of the British Journal of Pharmacology.
AB  - This themed issue of the British Journal of Pharmacology stems from the 7th in
      the series of meetings on the Molecular Pharmacology of G Protein-Coupled
      Receptors (MPGPCR) held at the Monash Institute of Pharmaceutical Sciences in
      Melbourne Australia from the 6th-8th December 2012.

PMID- 24575819
TI  - Ultrasound-guided proximal paravertebral anaesthesia in cattle.
AB  - OBJECTIVE: To develop and evaluate a method for ultrasound-guidance in performing
      the proximal paravertebral block for flank anaesthesia in cattle through a
      cadaveric study, followed by clinical application. STUDY DESIGN: prospective
      experimental cadaveric study and clinical series. ANIMALS: Previously frozen
      lumbar sections of cows without known spinal abnormalities were used. The
      clinical case group comprised of ten animals for which a right flank laparotomy
      was indicated. METHODS: Twenty cow cadavers were used to perform ultrasound
      guided bilateral injections of 1.0 mL dye (1.0 mL 1% Toluidine Blue in 1% Borax)
      at the intervertebral foramen at the level of T13, L1 and L2 spinal nerves.
      Distance and depth of injection, staining of the dorsal and ventral nerve
      branches, and deviation from the target were evaluated. The investigator's
      confidence as to visualisation and expected success at staining the nerve was
      assessed. Ten clinical cases received the ultrasound-guided proximal
      paravertebral anaesthesia. Analgesic success was evaluated using a 4-grade
      scoring system at 10 minutes after the injection and during surgery,
      respectively. Categorical variables were described using frequencies and
      proportions. RESULTS: Both dorsal and ventral branches of the spinal nerves T13,
      L1 or L2 were at least partially stained in 41% of injections, while in 77% of
      injections one of the branches was stained. Five out of ten clinical cases had a
      satisfactory anaesthesia. There was no significant association between confidence
      at injection and either staining or analgesic success. CONCLUSION: Results from
      the cadaveric and clinical study suggest no significant improvement using
      ultrasound guidance to perform proximal paravertebral block in cows compared to
      our previous clinical experience and to references in the literature using the
      blind method. CLINICAL RELEVANCE: Further research should be conducted to improve
      the ultrasound-guided technique described in this study.

PMID- 24575820
TI  - Survival of lung cancer patients in a resource-limited country.
AB  - AIM: Data on lung cancer survival are lacking in developing countries. Our
      objectives were to describe the survival of our lung cancer patients and to
      determine independent prognostic factors affecting survival. METHOD: All patients
      diagnosed with lung cancer from August 2007 to August 2010 were recruited from a
      single referral hospital of the state of Pahang, Malaysia. Detailed demographic
      data, ECOG (Eastern Cooperation Oncology Group) performance status, stage of
      disease and treatment were recorded. The date of histology or cytology
      confirmation was used as the date of entry. Survival time was calculated from the
      date of entry to the date of death. RESULTS: One hundred forty-nine patients were
      included for survival analysis. The median age was 62 years and patients were
      predominantly males (78%) and smokers (78%). The majority had non-small cell lung
      cancer (NSCLC) (94%); only six patients (4%) had small cell lung cancer. All
      patients presented with stage 3 or stage 4 disease. Overall median survival was
      18 weeks. "No definitive treatment" and "ECOG 3-4" were the significant
      independent predictors of death, with the hazard ratios of 2.1 (95% confidence
      interval [CI] 1.4, 3.0) and 1.6 (95% CI 1.1, 2.3) times, respectively. Among
      NSCLC patients on treatment, 1- and 2-year survival rates were 27% and 15%,
      respectively. CONCLUSION: The majority of lung cancer patients in Pahang
      presented with advanced disease. No definitive treatment and ECOG 3-4 were
      independent poor prognostic factors.

PMID- 24575821
TI  - Sonoelastography of the uterine cervix.

PMID- 24575822
TI  - Repeatability analysis of global and local metrics of brain structural networks.
AB  - Computational network analysis provides new methods to analyze the human
      connectome. Brain structural networks can be characterized by global and local
      metrics that recently gave promising insights for diagnosis and further
      understanding of neurological, psychiatric, and neurodegenerative disorders. In
      order to ensure the validity of results in clinical settings, the precision and
      repeatability of the networks and the associated metrics must be evaluated. In
      the present study, 19 healthy subjects underwent two consecutive measurements
      enabling us to test reproducibility of the brain network and its global and local
      metrics. As it is known that the network topology depends on the network density,
      the effects of setting a common density threshold for all networks were also
      assessed. Results showed good to excellent repeatability for global metrics,
      while for local metrics it was more variable and some metrics were found to have
      locally poor repeatability. Moreover, between-subjects differences were slightly
      inflated when the density was not fixed. At the global level, these findings
      confirm previous results on the validity of global network metrics as clinical
      biomarkers. However, the new results in our work indicate that the remaining
      variability at the local level as well as the effect of methodological
      characteristics on the network topology should be considered in the analysis of
      brain structural networks and especially in network comparisons.

PMID- 24575823
TI  - An autopsy case of familial amyotrophic lateral sclerosis with FUS R521G
      mutation.

PMID- 24575825
TI  - Effect of different numbers of -CH2- units on the performance of isoquinolinium
      dyes.
AB  - Three new dyes have been synthesized to investigate the influence of the distance
      between the electron acceptor and TiO2 surface on the performance of dye
      sensitized solar cells (DSSCs). In these dyes, the isoquinolinium acceptor, with
      a -(CH2)nCOOH anchoring group, and a functionalized triphenylamine donor are
      separated by an oligothiophene bridge. The physical and electrochemical
      properties of the dyes were investigated systematically. The results prove that
      different numbers of -CH2- units between the isoquinolinium acceptor and the
      carboxyl anchoring group have a less pronounced effect on the physical and
      electrochemical properties of these dyes. However, when applied in DSSCs, a sharp
      decrease in the short-circuit current (Jsc) was observed with increasing numbers
      of -CH2- units. For example, the device containing the organic dye bearing three 
      CH2- units produced the lowest Jsc of 7.94 mA.cm(-2). In contrast, the device
      containing the dye bearing only one -CH2- unit exhibited the highest Jsc of 13.88
      mA.cm(-2). The higher photocurrent obtained with the device incorporating the dye
      with one -CH2- unit resulted in a higher power conversion efficiency of 6.8%. 

PMID- 24575824
TI  - Detection of Francisella tularensis in voles in Finland.
AB  - Francisella tularensis is a highly virulent intracellular bacterium causing the
      zoonotic disease tularemia. It recurrently causes human and animal outbreaks in
      northern Europe, including Finland. Although F. tularensis infects several mammal
      species, only rodents and lagomorphs seem to have importance in its ecology. Peak
      densities of rodent populations may trigger tularemia outbreaks in humans;
      however, it is still unclear to which extent rodents or other small mammals
      maintain F. tularensis in nature. The main objective of this study was to obtain
      information about the occurrence of F. tularensis in small mammals in Finland. We
      snap-trapped 547 wild small mammals representing 11 species at 14 locations
      around Finland during 6 years and screened them for the presence of F. tularensis
      DNA using PCR analysis. High copy number of F. tularensis-specific DNA was
      detected in tissue samples of five field voles (Microtus agrestis) originating
      from one location and 2 years. According to DNA sequences of the bacterial 23S
      ribosomal RNA gene amplified from F. tularensis-infected voles, the infecting
      agent belongs to the subspecies holarctica. To find out the optimal tissue for
      tularemia screening in voles, we compared the amounts of F. tularensis DNA in
      lungs, liver, spleen, and kidney of the infected animals. F. tularensis DNA was
      detectable in high levels in all four organs except for one animal, whose kidney
      was F. tularensis DNA-negative. Thus, at least liver, lung, and spleen seem
      suitable for F. tularensis screening in voles. Thus, liver, lung, and spleen all
      seem suitable for F. tularensis screening in voles. In conclusion, field voles
      can be heavily infected with F. tularensis subsp. holarctica and thus potentially
      serve as the source of infection in humans and other mammals.

PMID- 24575826
TI  - Effects of vitamin E-coated dialyzer on oxidative stress and inflammation status
      in hemodialysis patients: a systematic review and meta-analysis.
AB  - BACKGROUND: Vitamin E-coated dialyzer may have an effect on oxidative stress and
      inflammation status in hemodialysis (HD) patients. Therefore, we performed a
      systematic review to assess the anti-oxidation and anti-inflammatory effects of
      vitamin E-coated dialyzer in HD patients. METHODS: The randomized controlled
      trials (RCTs) and quasi-RCTs of vitamin E-coated dialyzer versus conventional
      dialyzer for HD patients were searched from multiple databases. We screened
      relevant studies according to predefined inclusion criteria and performed meta
      analyses using RevMan 5.1 software. RESULTS: Meta-analysis showed vitamin E
      coated dialyzer therapy could significantly decrease the serum thiobarbituric
      acid reacting substances (TBARS) (SMD, -0.95; 95% CI, -1.28 to -0.61; p <
      0.00001), oxLDL (SMD, -0.61; 95% CI, -1.04 to -0.19; p = 0.005), interleukin-6
      (IL-6) (SMD, -0.65; 95% CI, -0.97 to -0.32; p < 0.0001) and C-reactive protein
      (CRP) levels (SMD, -0.46; 95% CI, -0.87 to -0.05; p = 0.03) compared with that of
      the control group. However, vitamin E-coated dialyzer did not result in
      increasing the total antioxidant status (TAS) (SMD, 0.23; 95% CI, -0.16 to 0.61;
      p = 0.25) and the fractional clearance of urea index (Kt/v) levels (MD, -0.07;
      95% CI, -0.14 to 0.00; p = 0.06), in addition, there was no significant
      difference in plasma superoxide dismutase (SOD) level compared with that of the
      conventional dialyzer & oral vitamin E group (SMD, 0.28; 95% CI, -0.20 to 0.75; p
      = 0.26). CONCLUSIONS: Vitamin E-coated dialyzer can reduce the oxidative stress
      and inflammation status reflected by the decreasing of serum TBARS, oxLDL, CRP,
      and IL-6 levels, and this new dialyzer does not affect the dialysis adequacy.

PMID- 24575827
TI  - Medical students' experiences learning intimate physical examination skills: a
      qualitative study.
AB  - BACKGROUND: Intimate physical examination skills are essential skills for any
      medical graduate to have mastered to an appropriate level for the safety of his
      or her future patients. Medical schools are entrusted with the complex task of
      teaching and assessing these skills for their students. The objectives of this
      study were to explore a range of medical students' experiences of learning
      intimate physical examination skills and to explore their perceptions of factors
      which impede or promote the learning of these skills. METHODS: Individual semi
      structured interviews (N = 16) were conducted with medical students in years two
      to five from the University of Newcastle, as part of a larger research project
      investigating how medical students develop their attitudes to gender and health.
      This was a self-selected sample of the entire cohort who were all invited to
      participate. A thematic analysis of the transcribed data was performed. RESULTS:
      Students reported differing levels of discomfort with their learning experiences
      in the area of intimate physical examination and differing beliefs about the
      helpfulness of these experiences. The factors associated with levels of
      discomfort and the helpfulness of the experience for learning were: satisfaction
      with teaching techniques, dealing with an uncomfortable situation and perceived
      individual characteristics in both the patients and the students. The examination
      causing the greatest reported discomfort was the female pelvic examination by
      male students. CONCLUSIONS: Student discomfort with the experience of learning
      intimate physical examination skills may be common and has ongoing repercussions
      for students and patients. Recommendations are made of ways to modify teaching
      technique to more closely match students' perceived needs.

PMID- 24575828
TI  - In vivo gene activity of human mesenchymal stem cells after scaffold-mediated
      local transplantation.
AB  - Functional activation of stem cells after transplantation is a main concern in
      stem cell therapy. For local transplantation, mesenchymal stem cells (MSCs) are
      usually administered via scaffolds, either by direct implantation or after
      preculturing of cells, and it is unclear which is better for the activation of
      transplanted cells. In this study, we investigated the in vivo gene expression
      activity of human MSCs (hMSCs) transplanted into calvarial defects either
      directly post-seeding on collagen sponges (Group 1) or after overnight in vitro
      culturing post-seeding (Group 2). Real-time reverse transcription-polymerase
      chain reaction at days 7 and 14 after transplantation identified a time
      dependent, rapid decrease in gene expression by the hMSCs, which in Group 1 was
      slightly more attenuated than in Group 2. Both groups exhibited a limited range
      of human-specific gene expression, which involved type I collagen (ColI),
      fibronectin, stromal cell-derived factor (SDF-1), and osteoprotegerin. Among
      these, ColI expression was the most efficient, with higher levels in Group 1 than
      Group 2. There was a lack of evidence for the expression of osteoblast
      differentiation-related markers or trophic factors, while resident cells showed
      clear expression of those genes. Rat-specific beta-actin expression in Group 2
      was least among the scaffold control, Group 1, and Group 2, and this pattern was
      repeated in the expression of other rat osteogenic genes. Group 1 transplants
      positively influenced the osteogenic process of the defect tissue in part, and
      rat IGF-1 expression was significantly increased in Group 1. This tendency of
      gene expression by hMSCs in a rat model was very similar to what was observed in
      transplantations using immunodeficient mice. The current study showed that a main
      gene expressed by transplanted hMSCs during the initial weeks following
      transplantation is ColI, with a lack of differentiation-related markers or growth
      factor expression by hMSCs. Our data suggest that direct transplantation of hMSCs
      loaded on a collagen sponge is more efficient for gene activation in transplanted
      hMSCs, and more favorable to the local host tissue than transplantation after
      preculturing of cells. 

PMID- 24575829
TI  - Swedish and American studies show that initiatives to decrease maternal obesity
      could play a key role in reducing preterm birth.
AB  - Maternal obesity is a major source of preventable perinatal morbidity, but
      studies of the relationship between obesity and preterm birth have been
      inconsistent. This review looks at two major studies covering just under 3.5
      million births, from California, USA, and Sweden. CONCLUSION: Inconsistent
      findings in previous studies appear to stem from the complex relationship between
      obesity and preterm birth. Initiatives to decrease maternal obesity represent an
      important strategy in reducing preterm birth.

PMID- 24575832
TI  - Unique features and insights from mucinous tumors of ovary in childhood:
      clinicopathological study of 15 cases including four premenarchal cases.
AB  - Mucinous tumors of ovary are primarily diagnosed in middle-aged and elder woman.
      They are very infrequent in the first two decades of life and exceedingly rare in
      premenarchal girls. We reviewed the past 20 years of our institutional pathology
      files and studied the clinicopathological features of the childhood ovarian
      mucinous tumor cases. The study concluded that ovarian mucinous tumor cases in
      childhood, including premenarchal cases, may not be as rare as people previously
      estimated and discovered some unique features of the tumors in this age group
      that are beneficial for better prognosis prediction and clinical management, as
      well as better understanding of pathogenesis of ovarian epithelial tumors. 

PMID- 24575831
TI  - Reliable differentiation of Meyerozyma guilliermondii from Meyerozyma caribbica
      by internal transcribed spacer restriction fingerprinting.
AB  - BACKGROUND: Meyerozyma guilliermondii (anamorph Candida guilliermondii) and
      Meyerozyma caribbica (anamorph Candida fermentati) are closely related species of
      the genetically heterogenous M. guilliermondii complex. Conventional phenotypic
      methods frequently misidentify the species within this complex and also with
      other species of the Saccharomycotina CTG clade. Even the long-established
      sequencing of large subunit (LSU) rRNA gene remains ambiguous. We also faced
      similar problem during identification of yeast isolates of M. guilliermondii
      complex from indigenous bamboo shoot fermentation in North East India. There is a
      need for development of reliable and accurate identification methods for these
      closely related species because of their increasing importance as emerging
      infectious yeasts and associated biotechnological attributes. RESULTS: We
      targeted the highly variable internal transcribed spacer (ITS) region (ITS1-5.8S
      ITS2) and identified seven restriction enzymes through in silico analysis for
      differentiating M. guilliermondii from M. caribbica. Fifty five isolates of M.
      guilliermondii complex which could not be delineated into species-specific
      taxonomic ranks by API 20 C AUX and LSU rRNA gene D1/D2 sequencing were subjected
      to ITS-restriction fragment length polymorphism (ITS-RFLP) analysis. TaqI ITS
      RFLP distinctly differentiated the isolates into M. guilliermondii (47 isolates)
      and M. caribbica (08 isolates) with reproducible species-specific patterns
      similar to the in silico prediction. The reliability of this method was validated
      by ITS1-5.8S-ITS2 sequencing, mitochondrial DNA RFLP and electrophoretic
      karyotyping. CONCLUSIONS: We herein described a reliable ITS-RFLP method for
      distinct differentiation of frequently misidentified M. guilliermondii from M.
      caribbica. Even though in silico analysis differentiated other closely related
      species of M. guilliermondii complex from the above two species, it is yet to be
      confirmed by in vitro analysis using reference strains. This method can be used
      as a reliable tool for rapid and accurate identification of closely related
      species of M. guilliermondii complex and for differentiating emerging infectious
      yeasts of the Saccharomycotina CTG clade.

PMID- 24575833
TI  - A microRNA meta-signature for pancreatic ductal adenocarcinoma.
AB  - Due to its aggressive and late presentation, there is an urgent need for novel
      and reliable biomarkers for the diagnosis and prognostication of pancreatic
      ductal adenocarcinoma (PDAC). MiRNAs have been extensively profiled in PDAC
      tissues, biopsies, blood samples and other biofluids and their expression levels
      compared to normal and chronic pancreatitis (CP) specimens in order to identify
      the most relevant candidates. Consolidation of these activities has not been
      attempted until now. The evaluated meta-review by Ma et al. helps to define the
      use of miRNAs as biomarkers for detecting this tumor-type and predicting survival
      outcomes in PDAC. Based on frequency and consistency between microarray studies,
      they identified a miRNA meta-signature for recognising PDAC: upregulation of miR
      21, 23a, 31, 100, 143, 155, and 221; with downregulation of miR-148a, 217 and
      375. Furthermore, they validated high miR-21, high miR-31 and low miR-375
      tumoural expression as independently prognostic for poor overall-survival (OS; n
      = 70).

PMID- 24575830
TI  - Molecular diagnostics on the toxigenic potential of Fusarium spp. plant
      pathogens.
AB  - AIMS: We propose and test an efficient and rapid protocol for the detection of
      toxigenic Fusarium isolates producing three main types of Fusarium-associated
      mycotoxins (fumonisins, trichothecenes and zearelanone). METHODS AND RESULTS: The
      novel approach utilizes partially multiplexed markers based on genes essential
      for mycotoxin biosynthesis (fumonisin--fum6, fum8; trichothecenes--tri5, tri6;
      zearalenone, zea2) in Fusarium spp. The protocol has been verified by screening a
      collection of 96 isolates representing diverse species of filamentous fungi. Each
      Fusarium isolate was taxonomically identified through both molecular and
      morphological techniques. The results demonstrate a reliable detection of
      toxigenic potential for trichothecenes (sensitivity 100%, specificity 95%),
      zearalenone (sensitivity 100%, specificity 100%) and fumonisins (sensitivity 94%,
      specificity 88%). Both presence and identity of toxin biosynthetic genes were
      further confirmed by direct sequencing of amplification products. CONCLUSIONS:
      The cross-species-specific PCR markers for key biosynthetic genes provide a
      sensitive detection of toxigenic fungal isolates, contaminating biological
      material derived from agricultural fields. SIGNIFICANCE AND IMPACT OF THE STUDY:
      The conducted study shows that a PCR-based assay of biosynthetic genes is a
      reliable, cost-effective, early warning system against Fusarium contamination.
      Its future use as a high-throughput detection strategy complementing chemical
      assays enables effective targeted application of crop protection products.

PMID- 24575834
TI  - Mentoring programs also required for children's homes.

PMID- 24575835
TI  - Cutaneous adverse effects of hormonal adjuvant therapy for breast cancer: a case
      of localised urticarial vasculitis following anastrozole therapy and a review of
      the literature.
AB  - Hormonal therapy with either tamoxifen or aromatase inhibitors is commonly used
      to treat women with breast cancer in both the adjuvant and recurrent disease
      setting. Cutaneous adverse reactions to these drugs have been rarely reported in
      the literature. We report an unusual case of urticarial vasculitis following the
      aromatase inhibitor anastrozole that localised to the unilateral trunk and
      mastectomy scar, and review the literature on the cutaneous adverse effects of
      hormonal therapy for breast cancer. 

PMID- 24575837
TI  - Designable architectures on nanoparticle surfaces: zirconium phosphate
      nanoplatelets as a platform for tetravalent metal and phosphonic acid assemblies.
AB  - Surface-functionalized zirconium phosphate (ZrP) nanoparticles were synthesized
      using a combination of ion exchange and self-assembly techniques. The surface of
      ZrP was used as a platform to deposit tetravalent metal ions by direct ion
      exchange with the protons of the surface phosphate groups. Subsequently,
      phosphonic acids were attached to the metal ion layer, effectively
      functionalizing the ZrP nanoparticles. Use of axially oriented bisphosphonic
      acids led to the ability to build layer-by-layer assemblies from the nanoparticle
      surface. Varying the metal ion and ligand used allowed designable architectures
      to be synthesized on the nanoparticle surface. X-ray powder diffraction, XPS,
      electron microprobe, solid-state NMR, FTIR, and TGA were used to characterize the
      synthesized materials. 

PMID- 24575836
TI  - The aetiopathogenesis of acne vulgaris - what's new?

PMID- 24575838
TI  - Hydatidiform mole: age-related clinical presentation and high rate of severe
      complications in older women.
AB  - OBJECTIVE: The purpose of this study was to demonstrate differences in clinical
      presentation of hydatidiform mole between women >=40 years and younger women.
      DESIGN: Retrospective study. SETTING: A tertiary referral unit in northern Italy.
      POPULATION: Three hundred and sixty-five women with hydatidiform mole were
      divided into group A (<40 years, 318 cases) and group B (>=40 years, 47 cases).
      METHODS: Clinical presentation between groups A and B was analyzed, also
      considering partial hydatidiform mole and complete hydatidiform mole. MAIN
      OUTCOME MEASURES: Differences in clinical presentation according to woman's age.
      RESULTS: In group B the diagnosis of hydatidiform mole at >=12 gestational weeks
      was more frequent (p < 0.001) and the detection of ultrasound features was higher
      (p < 0.05) than in group A. Vaginal bleeding (p < 0.05), increased uterine volume
      (p < 0.0001) and hyperemesis (p < 0.05) occurred more frequently in group B. In
      the women with complete hydatidiform mole, group B women presented with vaginal
      bleeding (p < 0.001), increased uterine volume (p < 0.05) and hyperemesis (p <
      0.05) more frequently than group A women. Complete hydatidiform mole was more
      commonly diagnosed after 12 weeks of gestation in group B (p < 0.0001). In women
      >=50 years, an increased rate of disease-related complications was detected.
      CONCLUSIONS: The clinical features of hydatidiform mole in women >=40 years are
      different from those seen in younger women. Failures in the early detection of
      hydatidiform mole in older women may expose them to a higher rate of severe
      complications.

PMID- 24575840
TI  - Is melatonin ready to be used in preterm infants as a neuroprotectant?
AB  - The prevention of neurological disabilities following preterm birth remains a
      major public health challenge and efforts are still needed to test the
      neuroprotective properties of candidate molecules. Melatonin serves as a
      neuroprotectant in adult models of cerebral ischemia through its potent
      antioxidant and anti-inflammatory effects. An increasing number of preclinical
      studies have consistently demonstrated that melatonin protects the damaged
      developing brain by preventing abnormal myelination and an inflammatory glial
      reaction, a major cause of white matter injury. The main questions asked in this
      review are whether preclinical data on the neuroprotective properties of
      melatonin are sufficient to translate this concept into the clinical setting, and
      whether melatonin can reduce white matter damage in preterm infants. This review
      provides support for our view that melatonin is now ready to be tested in human
      preterm neonates, and discusses ongoing and planned clinical trials. 

PMID- 24575839
TI  - Phospho-aspirin (MDC-22) inhibits breast cancer in preclinical animal models: an
      effect mediated by EGFR inhibition, p53 acetylation and oxidative stress.
AB  - BACKGROUND: The anticancer properties of aspirin are restricted by its
      gastrointestinal toxicity and its limited efficacy. Therefore, we synthesized
      phospho-aspirin (PA-2; MDC-22), a novel derivative of aspirin, and evaluated its
      chemotherapeutic and chemopreventive efficacy in preclinical models of triple
      negative breast cancer (TNBC). METHODS: Efficacy of PA-2 was evaluated in human
      breast cancer cells in vitro, and in orthotopic and subcutaneous TNBC xenografts
      in nude mice. Mechanistic studies were also carried out to elucidate the
      mechanism of action of PA-2. RESULTS: PA-2 inhibited the growth of TNBC cells in
      vitro more potently than aspirin. Treatment of established subcutaneous TNBC
      xenografts (MDA-MB-231 and BT-20) with PA-2 induced a strong growth inhibitory
      effect, resulting in tumor stasis (79% and 90% inhibition, respectively). PA-2,
      but not aspirin, significantly prevented the development of orthotopic MDA-MB-231
      xenografts (62% inhibition). Mechanistically, PA-2: 1) inhibited the activation
      of epidermal growth factor receptor (EGFR) and suppressed its downstream
      signaling cascades, including PI3K/AKT/mTOR and STAT3; 2) induced acetylation of
      p53 at multiple lysine residues and enhanced its DNA binding activity, leading to
      cell cycle arrest; and 3) induced oxidative stress by suppressing the thioredoxin
      system, consequently inhibiting the activation of the redox sensitive
      transcription factor NF-kappaB. These molecular alterations were observed in
      vitro and in vivo, demonstrating their relevance to the anticancer effect of PA
      2. CONCLUSIONS: Our findings demonstrate that PA-2 possesses potent
      chemotherapeutic efficacy against TNBC, and is also effective in its
      chemoprevention, warranting further evaluation as an anticancer agent.

PMID- 24575841
TI  - Synthesis, characterization, and biological affinity of a near-infrared-emitting
      conjugated oligoelectrolyte.
AB  - A near-IR-emitting conjugated oligoelectrolyte (COE), ZCOE, was synthesized, and
      its photophysical features were characterized. The biological affinity of ZCOE is
      compared to that of an established lipid-membrane-intercalating COE, DSSN+, which
      has blue-shifted optical properties making it compatible for tracking
      preferential sites of accumulation. ZCOE exhibits diffuse staining of E. coli
      cells, whereas it displays internal staining of select yeast cells which also
      show propidium iodide staining, indicating ZCOE is a "dead" stain for this
      organism. Staining of mammalian cells reveals complete internalization of ZCOE
      through endocytosis, as supported by colocalization with LysoTracker and late
      endosome markers. In all cases DSSN+ persists in the outer membranes, most likely
      due to its chemical structure more closely resembling a lipid bilayer. 

PMID- 24575843
TI  - A review of the integration of traditional, complementary and alternative
      medicine into the curriculum of South African medical schools.
AB  - BACKGROUND: Traditional, complementary and alternative (TCAM) medicine is
      consumed by a large majority of the South African population. In the context of
      increasing overall demand for healthcare this paper investigates the extent to
      which South African medical schools have incorporated TCAM into their curriculum
      because of the increased legislative and policy interest in formally
      incorporating TCAM into the health care system since democracy in 1994. METHODS:
      Heads of School from seven South African medical schools were surveyed
      telephonically. RESULTS: One school was teaching both Traditional African
      Medicine (TM) and CAM, five were teaching either TM or CAM and another was not
      teaching any aspect of TCAM. CONCLUSIONS: In conclusion, there is a paucity of
      curricula which incorporate TCAM. Medical schools have not responded to
      government policies or the contextual realities by incorporating TCAM into the
      curriculum for their students. South African medical schools need to review their
      curricula to increase their students' knowledge of TCAM given the demands of the
      population and the legislative realities.

PMID- 24575842
TI  - Distinct sets of Rab6 effectors contribute to ZW10--and COG-dependent Golgi
      homeostasis.
AB  - The organization of the Golgi apparatus is determined in part by the interaction
      of Rab proteins and their diverse array of effectors. Here, we used multiple
      approaches to identify and characterize a small subset of effectors that mimicked
      the effects of Rab6 on Golgi ribbon organization. In a visual-based, candidate
      protein screen, we found that the individual depletion of any of three Rab6
      effectors, myosin IIA (MyoIIA), Kif20A and Bicaudal D (BicD), was sufficient to
      suppress Golgi ribbon fragmentation/dispersal coupled to retrograde tether
      proteins in a manner paralleling Rab6. MyoIIA and Kif20A depletions were pathway
      selective and suppressed ZW10-dependent Golgi ribbon fragmentation/dispersal only
      whereas BicD depletion, like Rab6, suppressed both ZW10- and COG-dependent Golgi
      ribbon fragmentation. The MyoIIA effects could be produced in short-term assays
      by the reversible myosin inhibitor, blebbistatin. At the electron microscope
      level, the effects of BicD-depletion mimicked many of those of Rab6-depletion:
      longer and more continuous Golgi cisternae and a pronounced accumulation of
      coated vesicles. Functionally, BicD-depleted cells were inhibited in transport of
      newly synthesized VSV-G protein to the cell surface. In summary, our results
      indicate small, partially overlapping subsets of Rab6 effectors are
      differentially important to two tether-dependent pathways essential to Golgi
      organization and function. 

PMID- 24575845
TI  - Magnetism by interfacial hybridization and p-type doping of MoS(2) in
      Fe(4)N/MoS(2) superlattices: a first-principles study.
AB  - Magnetic and electronic properties of Fe4N(111)/MoS2(?3 * ?3) superlattices are
      investigated by first-principles calculations, considering two models: (I)
      Fe(I)Fe(II)-S and (II) N-S interfaces, each with six stacking configurations. In
      model I, strong interfacial hybridization between Fe(I)/Fe(II) and S results in
      magnetism of monolayer MoS2, with a magnetic moment of 0.33 MUB for Mo located on
      top of Fe(I). For model II, no magnetism is induced due to weak N-S interfacial
      bonding, and the semiconducting nature of monolayer MoS2 is preserved. Charge
      transfer between MoS2 and N results in p-type MoS2 with Schottky barrier heights
      of 0.5-0.6 eV. Our results demonstrate that the interfacial geometry and
      hybridization can be used to tune the magnetism and doping in Fe4N(111)/MoS2(?3 *
      ?3) superlattices. 

PMID- 24575844
TI  - Cartilage tissue engineering application of injectable gelatin hydrogel with in
      situ visible-light-activated gelation capability in both air and aqueous
      solution.
AB  - Chondroprogenitor cells encapsulated in a chondrogenically supportive, three
      dimensional hydrogel scaffold represents a promising, regenerative approach to
      articular cartilage repair. In this study, we have developed an injectable,
      biodegradable methacrylated gelatin (mGL)-based hydrogel capable of rapid
      gelation via visible light (VL)-activated crosslinking in air or aqueous
      solution. The mild photocrosslinking conditions permitted the incorporation of
      cells during the gelation process. Encapsulated human-bone-marrow-derived
      mesenchymal stem cells (hBMSCs) showed high, long-term viability (up to 90 days)
      throughout the scaffold. To assess the applicability of the mGL hydrogel for
      cartilage tissue engineering, we have evaluated the efficacy of chondrogenesis of
      the encapsulated hBMSCs, using hBMSCs seeded in agarose as control. The ability
      of hBMSC-laden mGL constructs to integrate with host tissues after implantation
      was further investigated utilizing an in vitro cartilage repair model. The
      results showed that the mGL hydrogel, which could be photopolymerized in air and
      aqueous solution, supports hBMSC growth and TGF-beta3-induced chondrogenesis.
      Compared with agarose, mGL constructs laden with hBMSCs are mechanically stronger
      with time, and integrate well with native cartilage tissue upon implantation
      based on push-out mechanical testing. VL-photocrosslinked mGL scaffold thus
      represents a promising scaffold for cell-based repair and resurfacing of
      articular cartilage defects. 

PMID- 24575846
TI  - Bartonella species in invasive rats and indigenous rodents from Uganda.
AB  - The presence of bartonellae in invasive rats (Rattus rattus) and indigenous
      rodents (Arvicanthis niloticus and Cricetomys gambianus) from two districts in
      Uganda, Arua and Zombo, was examined by PCR detection and culture. Blood from a
      total of 228 R. rattus, 31 A. niloticus, and 5 C. gambianus was screened using
      genus-specific primers targeting the 16S-23S intergenic spacer region.
      Furthermore, rodent blood was plated on brain heart infusion blood agar, and
      isolates were verified as Bartonella species using citrate synthase gene- (gltA)
      specific primers. One hundred and four fleas recovered from R. rattus were also
      tested for the presence of Bartonella species using the same gltA primer set. An
      overall prevalence of 1.3% (three of 228) was obtained in R. rattus, whereas
      61.3% of 31 A. niloticus and 60% of five C. gambianus were positive for the
      presence of Bartonella species. Genotypes related to Bartonella elizabethae, a
      known zoonotic pathogen, were detected in three R. rattus and one C. gambianus.
      Bartonella strains, similar to bacteria detected in indigenous rodents from other
      African countries, were isolated from the blood of A. niloticus. Bartonellae,
      similar to bacteria initially cultured from Ornithodorus sonrai (soft tick) from
      Senegal, were found in two C. gambianus. Interestingly, bartonellae detected in
      fleas from invasive rats were similar to bacteria identified in indigenous
      rodents and not their rat hosts, with an overall prevalence of 6.7%. These
      results suggest that if fleas are competent vectors of these bartonellae, humans
      residing in these two districts of Uganda are potentially at greater risk for
      exposure to Bartonella species from native rodents than from invasive rats. The
      low prevalence of bartonellae in R. rattus was quite surprising, in contrast, to
      the detection of these organisms in a large percentage of Rattus species from
      other geographical areas. A possible reason for this disparity is discussed.

PMID- 24575847
TI  - Myeloid dendritic cells type 2 after allergen inhalation in asthmatic subjects.
AB  - BACKGROUND: Dendritic cells (DCs) are professional antigen-presenting cells that
      mediate the response to inhaled allergen. A major division in DC ontogeny exists
      between myeloid DCs (mDCs) and plasmacytoid DCs (pDCs). A subtype of mDC
      expressing thrombomodulin, termed myeloid DCs type 2 (mDC2s), has been identified
      in both the circulation and lung and has recently been suggested to have a role
      in allergic asthma. OBJECTIVE: To investigate changes in circulating and sputum
      mDC2s after allergen inhalation in subjects with asthma. METHODS: Peripheral
      blood and induced sputum were obtained before and 3, 7, and 24 h after inhalation
      of diluent and allergen from allergic asthmatic subjects who develop both
      allergen-induced early- and late-phase responses. mDC2s were measured by flow
      cytometry. Soluble BDCA-3 (thrombomodulin) was measured in sputum by ELISA.
      RESULTS: The number of sputum mDC2s significantly increased 24 h after allergen
      challenge compared with diluent. The expression of BDCA-3 on sputum mDCs also
      increased, albeit non-significantly, at 7 and 24 h after allergen. Soluble BDCA-3
      in sputum and the number of circulating mDC2s were not different between allergen
      and diluent. CONCLUSIONS AND CLINICAL RELEVANCE: Myeloid DCs type 2 (mDC2s)
      increase in the sputum of subjects with asthma after allergen challenge,
      suggesting this subtype of mDC is involved in the regulation of allergen
      responses in the lung.

PMID- 24575848
TI  - Individual prediction model for lamivudine treatment response in hepatitis B
      virus e antigen-positive chronic hepatitis B patients.
AB  - BACKGROUND AND AIMS: Although prolonged lamivudine (LAM) therapy is associated
      with the emergence of LAM-resistant mutations, it is still a commonly used
      therapy in many Asian countries because of its established long-term safety and
      low cost. The aim of our study was to assess the predictors of long-term LAM
      treatment response and to establish an individual prediction model (IPM) for
      hepatitis B virus e antigen (HBeAg) seroconversion in HBeAg-positive chronic
      hepatitis B (CHB) patients. METHODS: This was a multicenter analysis of 838
      patients treated with LAM between January 1999 and August 2004. Of these, 748
      patients were followed up for at least 24 months. RESULTS: The median age was
      43.0 years (range, 19-79 years) and the mean duration of LAM monotherapy was 34.2
      +/- 0.7 months. In the multivariate analysis, age (odds ratio [OR] = 0.974, P <
      0.001), baseline alanine aminotransferase level (OR = 1.001, P = 0.014), and
      baseline hepatitis B virus DNA level (OR = 0.749, P < 0.001) were independent
      factors for HBeAg seroconversion. Based on the predictors, an IPM was
      established. Patients were classified into high (> 50%), intermediate (30-50%),
      or low (<= 30%) response groups based on their probability of HBeAg
      seroconversion according to the IPM. The cumulative HBeAg seroconversion rate at
      6 years for the high, intermediate, and low response groups was 66.0%, 48.5%, and
      21.8%, respectively (P < 0.001). CONCLUSIONS: An IPM was developed based on
      predictors of HBeAg seroconversion in HBeAg-positive CHB patients on LAM
      monotherapy. This model will allow screening of LAM responders prior to the
      commencement of antiviral treatment.

PMID- 24575849
TI  - Brain topological correlates of motor performance changes after repetitive
      transcranial magnetic stimulation.
AB  - Repetitive transcranial magnetic stimulation (rTMS) influences the brain
      temporally beyond the stimulation period and spatially beyond the stimulation
      site. Application of rTMS over the primary motor cortex (M1) has been shown to
      lead to plastic changes in interregional connectivity over the motor system as
      well as alterations in motor performance. With a sequential combination of rTMS
      over the M1 and functional magnetic resonance imaging (fMRI), we sought changes
      in the topology of brain networks and specifically the association of brain
      topological changes with motor performance changes. In a sham-controlled parallel
      group experimental design, real or sham rTMS was administered to each of the 15
      healthy subjects without prior motor-related dysfunctions, over the right M1 at a
      high frequency of 10 Hz. Before and after the intervention, fMRI data were
      acquired during a sequential finger motor task using the left, nondominant hand.
      Changes in the topology of brain networks were assessed in terms of global and
      local efficiency, which measures the efficiency in transporting information at
      global and local scales, respectively, provided by graph-theoretical analysis.
      Greater motor performance changes toward improvements after real rTMS were shown
      in individuals who exhibited more increases in global efficiency and more
      decreases in local efficiency. The enhancement of motor performance after rTMS is
      supposed to be associated with brain topological changes, such that global
      information exchange is facilitated, while local information exchange is
      restricted.

PMID- 24575850
TI  - Physiological and behavioural indices of hostility: an extension of the capacity
      model to include exposure to affective stress and right lateralized motor stress.
AB  - Right hemisphere functional cerebral systems have reliably been associated with
      sympathetic nervous system arousal and the perception of negative affective
      events. The goal of the current research was to provide additional support for
      the capacity model of hostility by examining changes attributable to functional
      cerebral systems within the right hemisphere using a dual concurrent task
      paradigm. To incorporate exposure to negative affective and right-lateralized
      motor stress using this approach, high and low hostile individuals completed a
      series of grip-strength tasks before and after hearing a recording of angry
      infant vocalizations. Results supported the capacity model in that high hostile
      individuals were unable to maintain regulatory control over right hemisphere
      activation as indicated through increased motor perseveration in the pre- and
      post-affective stress conditions, heightened systolic blood pressure (SBP) upon
      exposure to negative emotional sounds, and increased heart rate (HR) following
      stress. Conversely, low hostile individuals showed improved regulatory control
      over these regions as evidenced by reduced motor perseveration in the pre- and
      post-affective stress conditions, maintenance of SBP and reductions in HR
      following stress. The current data support the capacity model and extend its
      scope to include exposure to affective and right-lateralized motor stress. 

PMID- 24575852
TI  - Stratification of clear cell renal cell carcinoma by signaling pathway analysis.
AB  - Investigation of cell signaling pathways in 16 clear cell renal cell carcinomas
      to identify groups based on commonly shared phosphorylation-driven signaling
      networks. Using laser capture microdissection and reverse-phase protein arrays,
      we profiled 75 key nodes spanning signaling pathways important in tumorigenesis.
      Analysis revealed significantly different (P < 0.05) signaling levels for 27
      nodes between two groups of samples, designated A (4 samples; high EGFR, RET, and
      RASGFR1 levels, converging to activate AKT/mTOR) and B (12 samples; high ERK1/2
      and STAT phosphorylation). Group B was further partitioned into groups C (7
      samples; elevated expression of LC3B) and D (5 samples; activation of Src and
      STAT). Network analysis indicated that group A was characterized by signaling
      pathways related to cell cycle and proliferation, and group B by pathways related
      to cell death and survival. Homogeneous clear cell renal cell carcinomas could be
      stratified into at least two major functional groups. 

PMID- 24575851
TI  - The effects of labor and delivery on maternal and neonatal outcomes in term
      twins: a retrospective cohort study.
AB  - OBJECTIVE: To compare maternal and neonatal outcomes in twins undergoing a trial
      of labor versus pre-labor caesarean. DESIGN: Retrospective cohort study. SETTING:
      19 US hospitals from the Consortium on Safe Labor. POPULATION: Of 2225 twin sets
      >=36 weeks' gestation. METHODS: Maternal (abruption, estimated blood loss,
      postpartum haemorrhage, transfusion, chorioamnionitis, hysterectomy, ICU
      admission, death) and neonatal outcomes (birth injury, 5-minute Apgar <7, NICU
      admission, RDS, TTN, sepsis, asphyxia, NICU length of stay, death) were compared
      between the trial of labour and pre-labour caesarean groups with univariate and
      multivariate logistic and linear regression analyses. Similar analyses were
      performed for actual delivery modes. MAIN OUTCOME MEASURES: Maternal and neonatal
      outcomes. RESULTS: Among the 2225 twin sets, 1078 had a trial of labour, and
      65.9% of those delivered vaginally. There was an increased risk for postpartum
      haemorrhage [OR 2.5, 95% confidence interval (CI) 1.4-4.5] and blood transfusion
      (OR 1.9, 95%CI 1.2-3.2) for the trial of labour compared with pre-labour
      caesarean groups. Birth injury only occurred in the trial of labour group, 1%
      Twin A, 0.4% Twin B. Both twins had a higher risk of 5-minute Apgar <7 with trial
      of labour compared to pre-labour caesarean (A: OR 3.9, 95%CI 1.05-14.5; B: OR
      3.9, 95%CI 1.3-12.3). CONCLUSION: Term twins undergoing a trial of labour have
      increased maternal haemorrhage and transfusions along with neonatal birth trauma
      and lower Apgar scores, but these absolute neonatal occurrences were rare. Trial
      of labour in twins remains a safe and reasonable option in appropriately selected
      cases.

PMID- 24575853
TI  - The effects of low-level environmental tobacco smoke exposure on pulmonary
      function tests in preschool children with asthma.
AB  - OBJECTIVES: Though parents of children with asthma smoke, they often avoid
      smoking in their homes or near their children, thus limiting exposure. It is not
      known if such low-level environmental tobacco smoke (ETS) results in measurable
      exposure or affects lung function. The objectives of this study were to measure
      urinary cotinine in preschool children with asthma, and to examine the
      relationship between low-level ETS exposure and pulmonary function tests (PFTs).
      METHODS: Preschool children with asthma were enrolled. Parents completed
      questionnaires on ETS exposure and asthma control, urinary cotinine
      concentrations were measured and PFTs were compared between subjects with and
      without recent ETS exposure. RESULTS: Forty one subjects were enrolled. All
      parents denied smoking in their home within the last 2 weeks, but 14 (34%)
      parents admitted to smoking outside their homes or away from their children.
      Fifteen (37%; 95%CI: 23-53) of the children had urinary cotinine levels >=1
      ng/ml, of which seven (17%; 95%CI: 8-32) had levels >=5 ng/ml. FEV1 and FEV0.5
      were lower in subjects with a urinary cotinine level >=5 ng/ml as compared to
      those with levels <1 ng/ml or between 1 and 5 ng/ml; both at baseline and after
      inhalation of albuterol. Five of seven subjects with urinary cotinine levels >=5
      ng/ml had FEV0.5 less than 65% of predicted values. There were no significant
      differences in IOS measures. CONCLUSIONS: Despite parental denial of smoking near
      their children, preschool children may be exposed to ETS. Such low-level ETS
      exposure may affect lung function, possibly in a dose-dependent manner.

PMID- 24575854
TI  - Disease spectrum in patients with elevated serum tryptase levels.
AB  - BACKGROUND: Elevated serum tryptase levels can be a sign of mastocytosis, which
      is a rare disease associated with systemic and/or skin manifestations. OBJECTIVE:
      To investigate patients with elevated tryptase levels in regard to their
      underlying diseases, and to determine whether increased tryptase can be used as a
      diagnostic marker for underlying mastocytosis. METHODS: In a retrospective study
      the data of 96 patients with serum tryptase levels higher than 15 MUg/L were
      systematically analysed. In 48 patients control investigations for baseline
      tryptase were performed. RESULTS: Fifty-three of the 96 patients had tryptase
      levels >=20 MUg/L. A mere 16% of the 96 patients suffered from mastocytosis and
      had the highest tryptase levels (P < 0.001). The remaining patients had
      anaphylaxis (36%), urticaria and angioedema (26%), local reactions to insect
      bites (4%), drug reactions (3%), or miscellaneous diagnoses (15%). Only 16 of
      these had acute symptoms at tryptase investigation. In all, 48 patients had a
      follow up; in 7/48 patients with acute symptoms normal tryptase levels were seen
      at control investigations, but 41/48 (85%) patients showed continuously elevated
      tryptase levels >15 MUg/L and in 30 patients (62%) even values >20 MUg/L; 11 of
      these patients had anaphylaxis, five urticaria, five other diagnoses and nine
      patients mastocytosis. CONCLUSION: More than 50% of patients with non
      mastocytosis such as urticaria and angioedema, drug or anaphylactic reactions
      repeatedly had tryptase levels higher than 20 MUg/L. Since baseline tryptase >20
      MUg/L is a minor criterion for mastocytosis, these patients should be inspected
      for skin lesions of mastocytosis and receive a diagnostic body work-up for
      systemic mastocytosis including a bone marrow biopsy.

PMID- 24575856
TI  - An Initial lexicon of sensory properties for nail polish.
AB  - OBJECTIVE: The objective of this study was to develop an initial lexicon for
      sensory properties of nail polish and to validate this lexicon using a
      descriptive analysis study of selected samples. METHODS: Seventeen commercial
      products from four categories (regular, flake-containing, water-based and gel)
      were used in this study. Descriptive sensory analysis was conducted in this study
      to characterize and evaluate application and removal properties of these nail
      polishes. Data was then processed by ANOVA, Principal Component Analysis (PCA)
      and Pearson's Correlation Coefficient analysis to explore the differences among
      samples and attributes. RESULTS: A lexicon of 21 sensory attributes was developed
      to describe the application of nail polish. It included three initial texture
      attributes, thirteen initial appearance attributes and five aroma attributes. A
      lexicon of five attributes in five stages was developed to describe the removal
      of nail polish. The results from ANOVA and PCA showed that attributes in the
      lexicon separated the different product categories. CONCLUSION: The results of
      this study indicated that descriptive sensory analysis can be used to evaluate
      nail polish. The results of this study present scientists who are working on nail
      polish an additional tool to describe application and removal properties of nail
      polish.

PMID- 24575855
TI  - Blood expression levels of chemokine receptor CCR3 and chemokine CCL11 in age
      related macular degeneration: a case-control study.
AB  - BACKGROUND: Dysregulation of the CCR3/CCL11 pathway has been implicated in the
      pathogenesis of choroidal neovascularisation, a common feature of late age
      related macular degeneration (AMD). The aim of this study was to investigate the
      expression of CCR3 and its ligand CCL11 in peripheral blood in patients with
      neovascular AMD. METHODS: Patients with neovascular AMD and healthy controls were
      included. Blood samples were obtained and prepared for flow cytometry to
      investigate the expression of CCR3. Levels of CCL11 were measured in plasma using
      Cytometric Bead Array. Differences between the groups were tested using Kruskal
      Wallis test and Mann-Whitney U test. RESULTS: Patients (n = 83) with neovascular
      AMD and healthy control persons (n = 114) were included in the study. No
      significant difference in the expression of CCR3 was found on CD9+ granulocytes
      when comparing patients suffering from neovascular AMD with any of the control
      groups. We did not find any alteration in CCL11 levels in patients among the age
      matched groups. There was no correlation between expression of CCR3/CCL11 and
      clinical response to treatment with anti-vascular endothelial growth factor
      (VEGF). CONCLUSION: Our results do not suggest a systemic alteration of the
      CCR3/CCL11 receptor/ligand complex in patients with neovascular AMD.

PMID- 24575857
TI  - Deuterium studies reveal a new mechanism for the formose reaction involving
      hydride shifts.
AB  - In the formose reaction, formaldehyde is converted to glycolaldehyde, its dimer,
      under credible prebiotic conditions. Breslow proposed a mechanism for the process
      in 1959, but recent studies by Benner showed that it was wrong in detail. Our
      present studies clarify the mechanism, which involves the original Breslow
      intermediates but some different connecting steps. 

PMID- 24575858
TI  - Safety of botulinum toxin A in aesthetic treatments: a systematic review of
      clinical studies.
AB  - BACKGROUND: The use of botulinum toxin A (BoNT-A) for aesthetic treatments is
      growing steadily, and new safety data have been reported in recently published
      studies. OBJECTIVE: To investigate the safety data on the use of the three BoNT-A
      formulations approved for facial aesthetics from recent studies and to confirm
      their safety profiles. METHODS: The literature search was conducted using three
      online databases restricted to the timeframe from January 2000 to June 2012. Only
      clinical trials, randomized or open label, with safety as the primary or
      secondary endpoint, were included. RESULTS: Thirty-five papers were selected,
      with a total of subjects 8,787 studied. OnabotulinumtoxinA was used in 60.0% of
      the studies, abobotulinumtoxinA in 37.1%, and incobotulinumtoxinA in 2.8%. The
      glabella was the most investigated area (51.4%), followed by the upper face
      (25.7%), crow's feet (11.4%), and lower face (11.4%). Treatment-related adverse
      events were blepharoptosis (2.5%), brow ptosis (3.1%), and eye sensory disorders
      (3%) in the upper face and lip asymmetries and imbalances in the lower face
      (6.9%). All of these events resolved spontaneously. CONCLUSION: The short-term
      safety profile of BoNT-A in cosmetic nonsurgical procedures was confirmed for all
      the three commercial formulations.

PMID- 24575859
TI  - Monsoon harvests: the living legacies of rainwater harvesting systems in South
      India.
AB  - Rainwater harvesting, a "soft path" approach toward water management, is
      increasingly recognized as a key strategy toward ensuring food security and
      alleviating problems of water scarcity. Interestingly this "modern" approach has
      been in use for millennia in numerous older civilizations. This article uses
      India as a case study to explore the social, economic, and environmental
      dimensions of agricultural rainwater harvesting ponds, and evaluates the
      viability of these centuries-old systems under current climate and population
      pressures. A holistic watershed-scale approach that accounts for trade-offs in
      water availability and socioeconomic wellbeing is recommended for assessing the
      sustainability of these systems. 

PMID- 24575860
TI  - Consumer experience of formal crisis-response services and preferred methods of
      crisis intervention.
AB  - The manner in which people with mental illness are supported in a crisis is
      crucial to their recovery. The current study explored mental health consumers'
      experiences with formal crisis services (i.e. police and crisis assessment and
      treatment (CAT) teams), preferred crisis supports, and opinions of four
      collaborative interagency response models. Eleven consumers completed one-on-one,
      semistructured interviews. The results revealed that the perceived quality of
      previous formal crisis interventions varied greatly. Most participants preferred
      family members or friends to intervene. However, where a formal response was
      required, general practitioners and mental health case managers were preferred;
      no participant wanted a police response, and only one indicated a preference for
      CAT team assistance. Most participants welcomed collaborative crisis
      interventions. Of four collaborative interagency response models currently being
      trialled internationally, participants most strongly supported the Ride-Along
      Model, which enables a police officer and a mental health clinician to jointly
      respond to distressed consumers in the community. The findings highlight the
      potential for an interagency response model to deliver a crisis response aligned
      with consumers' preferences. 

PMID- 24575862
TI  - Implementing research findings to improve simulation-based training in emergency
      obstetric care.

PMID- 24575863
TI  - Facing up to stereotypes: surgeons and physicians are no different in their
      emotional expressiveness.
AB  - Of all the differences between surgeons and physicians that are discussed in the
      medical profession and in the community at large, one distinction stands out for
      its frequency of use: surgeons are less emotional than physicians, particularly
      in their relationships with patients. Here we tested this stereotype by analysing
      the portraits that 5914 surgeons and physicians had provided for patients to view
      when selecting a doctor. There is an asymmetry in the degree to which emotional
      information is conveyed by the face, with the right side being less expressive
      than the left. Hence, if the stereotype were true, surgeons would be more likely
      than physicians to show their right cheek in the photographs. While the results
      for doctors confirmed previous reports of a difference due to sex in which female
      doctors were more likely to show the left cheek than male doctors, we found that
      the doctors' specialization did not predict the way they turned in their
      portraits. Hence, the notion that surgeons face their patients less emotionally
      than physicians is not supported by the data. 

PMID- 24575861
TI  - Differential neuropathic pain sensitivity and expression of spinal mediators in
      Lewis and Fischer 344 rats.
AB  - BACKGROUND: Altered hypothalamo-pituitary-adrenal (HPA) axis activity may be
      accompanied by a modulation of pain sensitivity. In a model of neuropathic pain
      (chronic constriction injury, CCI) we investigated the onset and maintenance of
      mechanical allodynia/hyperalgesia and the expression of biochemical mediators
      potentially involved in spinal cell modulation in two rat strains displaying
      either hypo- (Lewis-LEW) or hyper- (Fischer 344-FIS) reactivity of the HPA axis.
      RESULTS: Mechanical pain thresholds and plasmatic corticosterone levels were
      assessed before and during periods of 4 or 21 days following CCI surgery. At the
      end of the respective protocols, the mRNA expression of glial cell markers (GFAP
      and Iba1) and glutamate transporters (EAAT3 and EAAT2) were examined. We observed
      a correlation between the HPA axis reactivity and the pain behavior but not as
      commonly described in the literature; LEW rats seemed to be less sensitive than
      FIS from 4 to 14 days after the CCI surgery when looking at the mechanical
      allodynia/hyperalgesia. However, the biochemical spinal markers expression we
      observed is conflicting. CONCLUSION: We did not find a specific causal relation
      between the pain behavior and the glial cell activation or the expression of the
      glutamate transporters, suggesting that the interaction between the HPA axis and
      the spinal activation pattern is more complex in a context of neuropathic pain.

PMID- 24575864
TI  - Bringing prosocial values to translational, disease-specific stem cell research.
AB  - BACKGROUND: Disease-specific stem cell therapies, created from induced
      pluripotent stem cell lines containing the genetic defects responsible for a
      particular disease, have the potential to revolutionize the treatment of
      refractory chronic diseases. Given their capacity to differentiate into any human
      cell type, these cell lines might be reprogrammed to correct a disease-causing
      genetic defect in any tissue or organ, in addition to offering a more clinically
      realistic model for testing new drugs and studying disease mechanisms. Clinical
      translation of these therapies provides an opportunity to design a more
      systematic, accessible and patient-influenced model for the delivery of medically
      innovative treatments to chronically ill patients. DISCUSSION: I focus on disease
      specific cell therapies because the types of patients who would benefit from them
      have congenital, severe, high-maintenance chronic conditions. They accordingly
      have a very strong claim for medical need and therapeutic intervention, must
      interact regularly with health providers, and so have the greatest stake in
      influencing, at a systemic level, the way their care is delivered. Given such
      patients' shared, aggregate needs for societal support and access to medical
      innovation, they constitute "patient communities". To reify the relevance of
      patient communities within a clinical context, I propose competitive grants or
      "prizes" to spur innovation in delivery of care, promoting "prosocial" values of
      transparency, equity, patient empowerment, and patient-provider and inter
      institutional collaboration. As facilitators of participant-driven advocacy for
      health and quality of life-improving measures, patient communities may be
      synergistic with the broad-based, geo-culturally embedded public health networks
      typically referred to as "communities" in the public health literature. SUMMARY:
      Prosocial values acquire a strong ethical justification based on shared need, and
      can be clearly defined as grant criteria, when applied to patients such as those
      who will benefit from disease-specific stem cell treatments. Within this context,
      prosociality aims not just to expand patients' treatment choices, but also their
      opportunities to take a more active role in the management of their own care and
      contribute towards shared goals through better-informed advocacy. Accordingly,
      prosociality promotes relational autonomy as well as other basic bioethical
      principles, including beneficence and a holistic, relational conception of human
      dignity.

PMID- 24575865
TI  - Epstein-Barr virus infection in children with renal transplantation: 17 years
      experience at a single center.
AB  - OBJECTIVES: The aim of this study was to detect the frequency, time of
      occurrence, management and outcome of Epstein-Barr virus (EBV) infection and
      related complications in pediatric renal transplant recipients. METHODS:
      Pediatric renal allograft recipients transplanted between August 1994 and
      December 2011 at our hospital was evaluated retrospectively. The patients were
      divided into two groups; Groups 1 and 2 were composed of patients transplanted
      before and after November 2007, respectively, when plasma EBV DNA levels were
      periodically measured. RESULTS: The study included 166 children, 89 (53.6%) boys,
      with a mean age of 12.2 +/- 3.8 years. Prior to transplantation, 144 patients
      (86.7%) were EBV seropositive. Within a median follow-up period of 36 months, 11
      of 22 seronegative children (50%) developed primary EBV infection. EBV
      reactivation was observed in 23 of 144 children (15.9%). Two patients with
      primary infection developed post-transplant lymphoproliferative disorder, one of
      whom died. Elevated serum creatinine levels or graft loss were not observed in
      any patient with EBV reactivation. CONCLUSIONS: EBV DNA monitoring by PCR in high
      risk pediatric renal transplant recipients will provide early diagnosis and
      treatment of EBV infections.

PMID- 24575866
TI  - Mineralizing angiopathy and minor head trauma.

PMID- 24575867
TI  - A tissue engineering approach for periodontal regeneration based on a
      biodegradable double-layer scaffold and adipose-derived stem cells.
AB  - Human and canine periodontium are often affected by an inflammatory pathology
      called periodontitis, which is associated with severe damages across tissues,
      namely, in the periodontal ligament, cementum, and alveolar bone. However, the
      therapies used in the routine dental practice, often consisting in a combination
      of different techniques, do not allow to fully restore the functionality of the
      periodontium. Tissue Engineering (TE) appears as a valuable alternative approach
      to regenerate periodontal defects, but for this purpose, it is essential to
      develop supportive biomaterial and stem cell sourcing/culturing methodologies
      that address the complexity of the various tissues affected by this condition.
      The main aim of this work was to study the in vitro functionality of a newly
      developed double-layer scaffold for periodontal TE. The scaffold design was based
      on a combination of a three-dimensional (3D) fiber mesh functionalized with
      silanol groups and a membrane, both made of a blend of starch and poly-E
      (caprolactone). Adipose-derived stem cells (canine adipose stem cells [cASCs])
      were seeded and cultured onto such scaffolds, and the obtained constructs were
      evaluated in terms of cellular morphology, metabolic activity, and proliferation.
      The osteogenic potential of the fiber mesh layer functionalized with silanol
      groups was further assessed concerning the osteogenic differentiation of the
      seeded and cultured ASCs. The obtained results showed that the proposed double
      layer scaffold supports the proliferation and selectively promotes the osteogenic
      differentiation of cASCs seeded onto the functionalized mesh. These findings
      suggest that the 3D structure and asymmetric composition of the scaffold in
      combination with stem cells may provide the basis for developing alternative
      therapies to treat periodontal defects more efficiently. 

PMID- 24575868
TI  - Direct comparison of the dynamics of IL-25- and 'allergen'-induced airways
      inflammation, remodelling and hypersensitivity in a murine asthma model.
AB  - BACKGROUND: Interleukin-25 has been implicated in the pathogenesis of asthma from
      studies on human asthmatics and in murine asthma models. OBJECTIVES: In this
      study, we hypothesized that chronic exposure of the airways to IL-25 alone is
      able to induce pathogenic changes observed in animal models of asthma. METHODS:
      We performed a detailed comparison of the dynamics of development of cellular
      infiltration, cytokine expression and airways remodelling and hyperresponsiveness
      in mice sensitized and challenged with OVA, a classical model of allergic asthma
      and those exposed to IL-25 alone. RESULTS: Intranasal challenge of BALB/c mice
      with IL-25 alone induced a delayed (compared with OVA-challenge), predominantly
      eosinophilic and lymphocytic infiltration into the airways lumen, along with
      increased production of Th2-type cytokines, chemokines and collagen, secretion of
      epithelial mucus, goblet cell hyperplasia, deposition of subepithelial collagen,
      airways smooth muscle cell hyperplasia and angiogenesis. Correspondingly, IL-25
      as well as OVA challenge both induced airways hyperresponsiveness and increased
      lung tissue damping. In contrast, IL-25 exposure did not increase IgE or IgG1
      production. CONCLUSIONS AND CLINICAL RELEVANCE: The data suggest that chronic
      airways exposure to IL-25 alone is sufficient to induce allergen- and IgE
      independent, asthma-like airways inflammation, remodelling and
      hyperresponsiveness in mice. Thus, IL-25 is a key molecular target in asthma,
      irrespective of the coexistence of IgE-dependent mechanisms.

PMID- 24575869
TI  - Probiotics and the BSH-related cholesterol lowering mechanism: a Jekyll and Hyde
      scenario.
AB  - Probiotic microorganisms have been documented over the past two decades to play a
      role in cholesterol-lowering properties via various clinical trials. Several
      mechanisms have also been proposed and the ability of these microorganisms to
      deconjugate bile via production of bile salt hydrolase (BSH) has been widely
      associated with their cholesterol lowering potentials in prevention of
      hypercholesterolemia. Deconjugated bile salts are more hydrophobic than their
      conjugated counterparts, thus are less reabsorbed through the intestines
      resulting in higher excretion into the feces. Replacement of new bile salts from
      cholesterol as a precursor subsequently leads to decreased serum cholesterol
      levels. However, some controversies have risen attributed to the activities of
      deconjugated bile acids that repress the synthesis of bile acids from
      cholesterol. Deconjugated bile acids have higher binding affinity towards some
      orphan nuclear receptors namely the farsenoid X receptor (FXR), leading to a
      suppressed transcription of the enzyme cholesterol 7-alpha hydroxylase (7AH),
      which is responsible in bile acid synthesis from cholesterol. This notion was
      further corroborated by our current docking data, which indicated that
      deconjugated bile acids have higher propensities to bind with the FXR receptor as
      compared to conjugated bile acids. Bile acids-activated FXR also induces
      transcription of the IBABP gene, leading to enhanced recycling of bile acids from
      the intestine back to the liver, which subsequently reduces the need for new bile
      formation from cholesterol. Possible detrimental effects due to increased
      deconjugation of bile salts such as malabsorption of lipids, colon
      carcinogenesis, gallstones formation and altered gut microbial populations, which
      contribute to other varying gut diseases, were also included in this review. Our
      current findings and review substantiate the need to look beyond BSH
      deconjugation as a single factor/mechanism in strain selection for
      hypercholesterolemia, and/or as a sole mean to justify a cholesterol-lowering
      property of probiotic strains. 

PMID- 24575870
TI  - Ebola virus vaccines: an overview of current approaches.
AB  - Ebola hemorrhagic fever is one of the most fatal viral diseases worldwide
      affecting humans and nonhuman primates. Although infections only occur frequently
      in Central Africa, the virus has the potential to spread globally and is
      classified as a category A pathogen that could be misused as a bioterrorism
      agent. As of today there is no vaccine or treatment licensed to counteract Ebola
      virus infections. DNA, subunit and several viral vector approaches, replicating
      and non-replicating, have been tested as potential vaccine platforms and their
      protective efficacy has been evaluated in nonhuman primate models for Ebola virus
      infections, which closely resemble disease progression in humans. Though these
      vaccine platforms seem to confer protection through different mechanisms, several
      of them are efficacious against lethal disease in nonhuman primates attesting
      that vaccination against Ebola virus infections is feasible. 

PMID- 24575871
TI  - Multicentre quality control evaluation of different biomarker candidates for
      amyotrophic lateral sclerosis.
AB  - Abstract Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron
      disease that mainly causes degeneration of the upper and lower motor neurons,
      ultimately leading to paralysis and death within three to five years after first
      symptoms. The pathological mechanisms leading to ALS are still not completely
      understood. Several biomarker candidates have been proposed in cerebrospinal
      fluid (CSF). However, none of these has successfully translated into clinical
      routine. Part of the reason for this failure to translate may relate to
      differences across laboratories. For this reason, several of the most commonly
      used ALS biomarker candidates were evaluated on clinically well-defined ALS
      samples from six European centres in a multicentre sample-collection approach
      with centralized sample processing. Results showed that phosphorylated
      neurofilament heavy chain differentiated between ALS and control cases in all
      centres. We therefore propose that measurement of phosphorylated neurofilaments
      in CSF is the most promising candidate for translation into the clinical setting
      and might serve as a benchmark for other biomarker candidates. 

PMID- 24575873
TI  - Application of biuret, dicyandiamide, or urea as a cathode buffer layer toward
      the efficiency enhancement of polymer solar cells.
AB  - Three amino-containing small-molecule organic materials-biuret, dicyandiamide
      (DCDA), and urea-were successfully applied as novel cathode buffer layers (CBLs)
      in P3HT:PCBM bulk heterojunction polymer solar cells (BHJ-PSCs) for the first
      time, resulting in obvious efficiency enhancement. Under the optimized condition,
      the power conversion efficiencies (PCEs) of the CBL-incorporated BHJ-PSC devices
      are 3.84%, 4.25%, and 4.39% for biuret, DCDA, and urea, which are enhanced by
      ~15%, ~27%, and ~31%, respectively, compared to the reference poly(3
      hexylthiophene-2,5-diyl) : [6,6]-phenyl-C61-butyric acid methyl ester (P3HT:PCBM)
      BHJ-PSC device without any CBL. The efficiency enhancement is primarily
      attributed to the increases of both short-circuit current density (Jsc) and fill
      factor (FF), for which the enhancement ratio is found to be sensitively dependent
      on the molecular structure of small-molecule organic materials. The surface
      morphologies and surface potential changes of the CBL-incorporated P3HT:PCBM
      photoactive layers were studied by atomic force microscopy and scanning Kelvin
      probe microscopy, respectively, suggesting the formation of an interfacial dipole
      layer between the photoactive layer and Al cathode, which may decrease the energy
      level offset between the work function of Al and the lowest unoccipoed molecular
      orbital level (LUMO) of the PCBM acceptor and consequently facilitate electron
      extraction by the Al cathode. The difference in the enhancement effect of biuret,
      DCDA, and urea is due to their difference on the work function matching with
      P3HT:PCBM. Besides, the coordination interaction between the lone-pair electrons
      on the N atoms of the amino (-NH2) group and the Al atoms may prohibit
      interaction between Al and the thiophene rings of P3HT, contributing to the
      efficiency enhancement of the CBL-incorporated devices as well. In this sense,
      the different CBL performance of biuret, DCDA, and urea is also proposed to
      partially originate from the differences on their chemical structure,
      specifically the number of amino groups. 

PMID- 24575874
TI  - Enhanced reproducibility of the human gel-based tear proteome maps in the
      presence of di-(2-hydroxyethyl) disulfide.
AB  - Patterns obtained in two-dimensional gel electrophoresis (2-DE) in the previously
      published articles suggest a varying number of proteins. To seek the cause of
      this variation, we investigated the effect of reduction power on the overall tear
      proteome maps. To this end, the buffers of two reducing agents, dithiothreitol
      (DTT) at nine different concentrations and di-(2-hydroxyethyl) disulfide (HED),
      were examined. The assay showed that HED clearly improved 2-DE resolution,
      increased the number of detectable protein spots, and offered well-resolved chain
      regions in comparison with those treated with DTT. Furthermore, this study
      introduced increasing the reduction power as a remedy to increase the
      reproducibility of two-dimensional human tear proteome maps. In addition, the
      results of our assessment showed that improved reduction efficiency was
      accompanied by increased procedure reproducibility from 42% to 89%. 

PMID- 24575872
TI  - Clinical determinants of a positive visual inspection after treatment with acetic
      acid for cervical cancer screening.
AB  - OBJECTIVE: To examine the determinants of a positive visual inspection after
      acetic acid (VIA), including the relationship of testing positive for high-risk
      human papillomavirus (HR-HPV), which is the necessary cause of cervical cancer.
      DESIGN: A prospective cohort study. SETTING: Three clinical sites in rural China.
      POPULATION: A total of 7541 women aged 25-65 years. METHODS: All women underwent
      VIA, DNA testing, by two DNA tests performed on both clinician- and self
      collected specimens, and HPV E6 oncoprotein testing. Those positive by any test
      underwent colposcopy and four-quadrant biopsy evaluation. A random sample of
      women with negative screening results also underwent colposcopy and, if
      colposcopic abnormalities were observed, four-quadrant biopsy evaluation was
      performed. Women diagnosed with cervical intraepithelial neoplasia grade 2
      (CIN2), or more severe grades (CIN2 + ), underwent treatment. MAIN OUTCOME
      MEASURE: Testing positive for VIA. RESULTS: Overall, 7.6% (95% confidence
      interval, 95% CI, 7.0-8.2%) had a positive VIA. Women who tested positive for HPV
      were more likely to have a positive VIA than women who tested negative for HPV
      (15.0%, 95% CI 12.9-17.2% versus 6.3%, 95% CI 5.7-6.9%; P < 0.001). Older women
      were less likely to have a positive VIA (Ptrend  < 0.001), including women with
      CIN2 +  (Ptrend  < 0.001). A logistic regression model demonstrated that
      diagnosis (CIN2 +  versus <CIN2; odds ratio, OR, 32; 95% CI 11-100), testing HPV
      positive with a higher viral load (highest versus lowest; OR 4.3; 95% CI 2.5
      7.4), and age (51 years and older versus <38 years; OR 0.22; 95% CI 0.17-0.30)
      were independent determinants of having a positive VIA. VIA was more likely to be
      positive for women with CIN2 + having an abnormal colposcopic impression versus
      women with CIN2 +  regardless of colposcopic impression (71.4 versus 47.2%).
      CONCLUSIONS: The age of the population and method of disease ascertainment should
      be considered in the interpretation of any VIA performance.

PMID- 24575876
TI  - Polarity-driven polytypic branching in cu-based quaternary chalcogenide
      nanostructures.
AB  - An appropriate way of realizing property nanoengineering in complex quaternary
      chalcogenide nanocrystals is presented for Cu2CdxSnSey(CCTSe) polypods. The
      pivotal role of the polarity in determining morphology, growth, and the polytypic
      branching mechanism is demonstrated. Polarity is considered to be responsible for
      the formation of an initial seed that takes the form of a tetrahedron with four
      cation-polar facets. Size and shape confinement of the intermediate
      pentatetrahedral seed is also attributed to polarity, as their external facets
      are anion-polar. The final polypod extensions also branch out as a result of a
      cation-polarity-driven mechanism. Aberration-corrected scanning transmission
      electron microscopy is used to identify stannite cation ordering, while ab initio
      studies are used to show the influence of cation ordering/distortion,
      stoichiometry, and polytypic structural change on the electronic band structure. 

PMID- 24575877
TI  - Disruption of the gastroesophageal junction by central obesity and waist belt:
      role of raised intra-abdominal pressure.
AB  - Obesity is a major reason for the recent increase in incidence of reflux disease
      and cancers at the distal esophagus and gastroesophageal junction (GOJ) and is
      mediated through a rise in the intra-abdominal pressure (IAP) but the exact
      mechanisms are unclear. Raised IAP from obesity and with application of waist
      belt produces mechanical distortion of the GOJ through formation of partial
      hiatus hernia. Even though there is no trans-sphincteric acid reflux, there is
      increased ingress of acid into the lower sphincter (intra-sphincteric reflux) as
      a consequence of raised IAP. In addition, short segment acid reflux is more
      evident in obese subjects with a belt on. Acid pocket is also enlarged in hiatus
      hernia, and acts as a reservoir of acid available to reflux whenever the
      sphincter fails. Above mechanisms may explain the common occurrence of cardiac
      lengthening and inflammation found in asymptomatic obese subjects. The inflamed
      cardia is also immunohistochemically similar to non-intestinal Barrett's mucosa,
      which is of etiological importance for cancers at the GOJ. Interventions that can
      reduce the mechanical distortion and acid exposure at the GOJ, including diet,
      exercise, drugs, sphincter augmentation therapy, and surgery, are clinically
      relevant in the treatment of gastroesophageal reflux disease but more data are
      needed whether if these strategies are also effective in preventing cancer. As a
      conclusion, raised IAP produces silent mechanical disruption of the GOJ, which
      may explain the high occurrence of cancers in this region and it is potentially
      reversible with early interventions.

PMID- 24575875
TI  - Library synthesis, screening, and discovery of modified Zinc(II)
      Bis(dipicolylamine) probe for enhanced molecular imaging of cell death.
AB  - Zinc(II)-bis(dipicolylamine) (Zn-BDPA) coordination complexes selectively target
      the surfaces of dead and dying mammalian cells, and they have promise as
      molecular probes for imaging cell death. A necessary step toward eventual
      clinical imaging applications is the development of next-generation Zn-BDPA
      complexes with enhanced affinity for the cell death membrane biomarker,
      phosphatidylserine (PS). This study employed an iterative cycle of library
      synthesis and screening, using a novel rapid equilibrium dialysis assay, to
      discover a modified Zn-BDPA structure with high and selective affinity for
      vesicles containing PS. The lead structure was converted into a deep-red
      fluorescent probe and its targeting and imaging performance was compared with an
      unmodified control Zn-BDPA probe. The evaluation process included a series of
      FRET-based vesicle titration studies, cell microscopy experiments, and rat tumor
      biodistribution measurements. In all cases, the modified probe exhibited
      comparatively higher affinity and selectivity for the target membranes of dead
      and dying cells. The results show that this next-generation deep-red fluorescent
      Zn-BDPA probe is well suited for preclinical molecular imaging of cell death in
      cell cultures and animal models. Furthermore, it should be possible to substitute
      the deep-red fluorophore with alternative reporter groups that enable clinically
      useful, deep-tissue imaging modalities, such as MRI and nuclear imaging. 

PMID- 24575879
TI  - Cesarean section and different circumstances of the obstetric field among
      countries.

PMID- 24575878
TI  - Enhanced sun protection of nano-sized metal oxide particles over conventional
      metal oxide particles: an in vitro comparative study.
AB  - BACKGROUND: A systematic and detailed study has been designed and conducted,
      taking into account some of the proposed benefits such as increased efficiency,
      transparency, unique texture, protection of active ingredient and higher consumer
      compliance of cosmetics containing nano-sized metal oxides. METHODS: This study
      also presents an in vitro method to determine sun protection factor of the
      investigational sunscreen cream samples containing zinc oxide and titanium
      dioxide with a varied range of particle size. Finally, a comparative study has
      been conducted between metal oxide particles, conventional as well as
      nanoparticles. RESULTS: All the skin cosmetics formulated were thermally stable
      with a pH ranging from 7.9 to 8.2. Moreover, the fatty acid substance content and
      residue were found to be analogous to the standard values in each skin cosmetic.
      The skin cosmetics containing the titanium or zinc oxide nanoparticles were found
      to have improved spreadability as compared to skin cosmetics containing
      conventional titanium or zinc oxide particles, respectively. All skin cosmetics
      were found to have uniform distribution of the particles. The sunscreen creams
      containing zinc oxide nanoparticles and titanium dioxide nanoparticles were found
      to have higher in vitro sun protection factor (SPF of 3.65 for ZnO nanoparticles
      and 4.93 for TiO2 nanoparticles) as compared to that of sunscreen creams
      containing conventional zinc oxide particles (SPF = 2.90) and conventional
      titanium dioxide (SPF = 1.29), clearly indicating the effect of reduction in
      particles size, from micro to nano, on the sun protection factor. CONCLUSION:
      Good texture, better spreadability and enhanced in vitro SPF proved the
      advantageous role of nanoparticles in cosmetics.

PMID- 24575880
TI  - The association of serum inflammatory biomarkers with chronic kidney disease in
      hypertensive patients.
AB  - A positive association between inflammation and chronic kidney disease (CKD) has
      been reported but the impact of hypertension on this relation remains unclear.
      The aim of this study is to investigate the association of various inflammation
      markers with risk of CKD in hypertensive patients. 387 hypertensive patients
      (mean age 55.5 years) were recruited. Serum matrix metalloproteinase-2 (MMP-2),
      matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1(TIMP
      1), high-sensitivity C-reactive protein (hsCRP) and osteopontin (OPN) were
      measured by ELISA. CKD was diagnosed either as evidence of kidney damage,
      including microalbuminuria, or by low glomerular filtration rate (GFR) (<60
      mL/min/1.73 m(2)), which was estimated using the Modification of Diet in Renal
      Disease (MDRD) abbreviated equation. Compared with the reference groups (eGFR >=
      60 mL/min/1.73 m(2)), the serum levels of TIMP-1, OPN, hsCRP were significantly
      higher, and the MMP-9/TIMP-1 ratio was lower in the risk group (eGFR < 60
      mL/min/1.73 m(2)). Multiple logistic regression analysis showed that TIMP-1, MMP
      9/TIMP-1 ratio, OPN and hsCRP were associated with low GFR separately after
      adjustment, whereas MMP-9/TIMP-1 ratio, OPN and hsCRP were associated with
      microalbuminuria. The significant association of MMP-9/TIMP-1 ratio and OPN with
      low GFR and microalbuminuria persisted after additional adjustment for other
      studied inflammatory biomarkers. Our data suggest that inflammation is strongly
      and independently associated with renal damage in hypertensive patients. MMP
      9/TIMP-1 ratio and OPN may serve as novel risk factors and therapeutic targets
      for the treatment of CKD in hypertensive patients.

PMID- 24575881
TI  - Lichen planopilaris after imiquimod 5% cream for multiple BCC in basal cell
      naevus syndrome.
AB  - Basal cell naevus syndrome is an inherited autosomal dominant genetic disorder
      characterised by multiple basal cell carcinomas (BCC), skeletal, neurological and
      opthalmological abnormalities. The treatment of choice of the often multiple and
      large BCC consists of a combined approach including surgery, liquid nitrogen and
      other topical treatment modalities. Imiquimod 5% cream is an immune-response
      modifying drug with antiviral and anti-tumour activity. Recent reports have
      associated the immune-stimulant properties of imiquimod with the exacerbation of
      several autoimmune skin diseases, such as eczema, psoriasis, vitiligo and
      lichenoid dermatitis. Here we report a patient with basal cell naevus syndrome
      who developed a lichen planopilaris on the same site of the scalp, which had been
      previously treated with two cycles of imiquimod for multiple BCC. 

PMID- 24575883
TI  - Therapeutic engagement between consumers in suicidal crisis and mental health
      nurses.
AB  - Registered nurses within public mental health services play crucial roles in
      helping people recover from suicidal crisis. However, there is a lack of
      understanding of how care is experienced in this context, and available evidence
      suggests that nurses and consumers are often dissatisfied with the quality of
      care. There is thus an imperative to generate understanding of needs and
      experiences of both groups with a view to informing practice development. This
      article summarizes qualitative findings from a multimethod study undertaken in
      Australia, which surveyed and interviewed mental health nurses who had recent
      experience of caring for consumers in suicidal crisis in a hospital setting, and
      interviewed consumers who had recovered from a recent suicidal crisis. A
      framework was developed to guide the study and support ethical imperatives; in
      particular, the promotion of consumer well-being. The findings highlight that
      therapeutic interpersonal engagement between nurses and consumers was central to
      quality care. This was particularly noted, as engagement could help reduce
      consumer isolation, loss of control, distress, and objectification of the
      delivery of potentially-objectifying common interventions. Of concern, the
      results indicate a lack of therapeutic engagement from the perspective of both
      consumers and nurses. Recommendations to promote fuller therapeutic engagement
      are presented. 

PMID- 24575882
TI  - The effect of a decision aid intervention on decision making about coronary heart
      disease risk reduction: secondary analyses of a randomized trial.
AB  - BACKGROUND: Decision aids offer promise as a practical solution to improve
      patient decision making about coronary heart disease (CHD) prevention medications
      and help patients choose medications to which they are likely to adhere. However,
      little data is available on decision aids designed to promote adherence. METHODS:
      In this paper, we report on secondary analyses of a randomized trial of a CHD
      adherence intervention (second generation decision aid plus tailored messages)
      versus usual care in an effort to understand how the decision aid facilitates
      adherence. We focus on data collected from the primary study visit, when
      intervention participants presented 45 minutes early to a previously scheduled
      provider visit; viewed the decision aid, indicating their intent for CHD risk
      reduction after each decision aid component (individualized risk assessment and
      education, values clarification, and coaching); and filled out a post-decision
      aid survey assessing their knowledge, perceived risk, decisional conflict, and
      intent for CHD risk reduction. Control participants did not present early and
      received usual care from their provider. Following the provider visit,
      participants in both groups completed post-visit surveys assessing the number and
      quality of CHD discussions with their provider, their intent for CHD risk
      reduction, and their feelings about the decision aid. RESULTS: We enrolled 160
      patients into our study (81 intervention, 79 control). Within the decision aid
      group, the decision aid significantly increased knowledge of effective CHD
      prevention strategies (+21 percentage points; adjusted p<.0001) and the accuracy
      of perceived CHD risk (+33 percentage points; adjusted p<.0001), and
      significantly decreased decisional conflict (-0.63; adjusted p<.0001). Comparing
      between study groups, the decision aid also significantly increased CHD
      prevention discussions with providers (+31 percentage points; adjusted p<.0001)
      and improved perceptions of some features of patient-provider interactions.
      Further, it increased participants' intentions for any effective CHD risk
      reducing strategies (+21 percentage points; 95% CI 5 to 37 percentage points),
      with a majority of the effect from the educational component of the decision aid.
      Ninety-nine percent of participants found the decision aid easy to understand and
      93% felt it easy to use. CONCLUSIONS: Decision aids can play an important role in
      improving decisions about CHD prevention and increasing patient-provider
      discussions and intent to reduce CHD risk.

PMID- 24575885
TI  - Comparison of the Glidescope(r), flexible fibreoptic intubating bronchoscope,
      iPhone modified bronchoscope, and the Macintosh laryngoscope in normal and
      difficult airways: a manikin study.
AB  - BACKGROUND: Smart phone technology is becoming increasingly integrated into
      medical care.Our study compared an iPhone modified flexible fibreoptic
      bronchoscope as an intubation aid and clinical teaching tool with an unmodified
      bronchoscope, Glidescope(r) and Macintosh laryngoscope in a simulated normal and
      difficult airway scenario. METHODS: Sixty three anaesthesia providers, 21
      consultant anaesthetists, 21 registrars and 21 anaesthetic nurses attempted to
      intubate a MegaCode KellyTM manikin, comparing a normal and difficult airway
      scenario for each device. Primary endpoints were time to view the vocal cords
      (TVC), time to successful intubation (TSI) and number of failed intubations with
      each device. Secondary outcomes included participant rated device usability and
      preference for each scenario. Advantages and disadvantages of the iPhone modified
      bronchoscope were also discussed. RESULTS: There was no significant difference in
      TVC with the iPhone modified bronchoscope compared with the Macintosh blade (P =
      1.0) or unmodified bronchoscope (P = 0.155). TVC was significantly shorter with
      the Glidescope compared with the Macintosh blade (P < 0.001), iPhone (P < 0.001)
      and unmodified bronchoscope (P = 0.011). The iPhone bronchoscope TSI was
      significantly longer than all other devices (P < 0.001). There was no difference
      between anaesthetic consultant or registrar TVC (P = 1.0) or TSI (P = 0.252),
      with both being less than the nurses (P < 0.001). Consultant anaesthetists and
      nurses had a higher intubation failure rate with the iPhone modified bronchoscope
      compared with the registrars. Although more difficult to use, similar proportions
      of consultants (14/21), registrars (15/21) and nurses (15/21) indicated that they
      would be prepared to use the iPhone modified bronchoscope in their clinical
      practice. The Glidescope was rated easiest to use (P < 0.001) and was the
      preferred device by all participants for the difficult airway scenario.
      CONCLUSIONS: The iPhone modified bronchoscope, in its current configuration, was
      found to be more difficult to use compared with the Glidescope(r) and unmodified
      bronchoscope; however it offered several advantages for teaching fibreoptic
      intubation technique when video-assisted bronchoscopy was unavailable.

PMID- 24575884
TI  - The association of serum 25-OH vitamin D with atopy, asthma, and lung function in
      a prospective study of Danish adults.
AB  - BACKGROUND: Besides the important skeletal functions, it has been suggested that
      vitamin D is involved in the pathogenesis of allergy and asthma and related to
      lung function. However, previous studies are inconclusive. OBJECTIVE: The purpose
      of this study was to investigate associations of serum levels of 25-hydroxy
      vitamin D (25(OH)D) with atopy, asthma, and lung function in a prospective study
      of Danish adults. METHODS: This study included 4999 adults aged 30-60 years in
      1999-2001. Three thousand and thirty-two of those included at baseline also
      participated at a follow-up examination 5 years later, and 3727 answered a 10
      year follow-up questionnaire. Serum levels of (25(OH)D) were measured by high
      performance liquid chromatography (HPLC) at baseline. No information on use of
      vitamin D supplements was available. Specific IgE against four common antigens
      was measured. Information about doctor-diagnosed asthma was obtained from
      questionnaires, and lung function (FEV1 and forced vital capacity) was measured
      by spirometry. RESULTS: We found no significant associations of 25(OH)D with
      atopy and doctor-diagnosed asthma. However, we found that low levels of 25(OH)D
      were associated with lower FEV1 percentage predicted (FEV1%pred) in the cross
      sectional analyses. The odds ratio (OR) of FEV1%pred < 80% among participants in
      the highest quartile of 25(OH)D compared with those in the lowest was 0.66 (95%
      confidence interval (CI): 0.49-0.74). In contrast, prospective analyses indicated
      an association between high levels of 25(OH)D at baseline and adverse changes in
      lung function. OR (95%CI) of incident FEV1%pred < 80% was 1.73 (1.06-2.82) in the
      highest quartile of 25(OH)D compared with the lowest. CONCLUSIONS AND CLINICAL
      RELEVANCE: Our data indicates that 25(OH)D levels do not influence the
      development of asthma and allergy among adults. Further, the results did not
      consistently support that 25(OH)D levels associate with lung function. Randomized
      controlled trials are needed to further address this issue.

PMID- 24575886
TI  - Overcoming fixation with repeated memory suppression.
AB  - Fixation (blocks to memories or ideas) can be alleviated not only by encouraging
      productive work towards a solution, but, as the present experiments show, by
      reducing counterproductive work. Two experiments examined relief from fixation in
      a word-fragment completion task. Blockers, orthographically similar negative
      primes (e.g., ANALOGY), blocked solutions to word fragments (e.g., A_L_ _GY) in
      both experiments. After priming, but before the fragment completion test,
      participants repeatedly suppressed half of the blockers using the Think/No-Think
      paradigm, which results in memory inhibition. Inhibiting blockers did not
      alleviate fixation in Experiment 1 when conscious recollection of negative primes
      was not encouraged on the fragment completion test. In Experiment 2, however,
      when participants were encouraged to remember negative primes at fragment
      completion, relief from fixation was observed. Repeated suppression may nullify
      fixation effects, and promote creative thinking, particularly when fixation is
      caused by conscious recollection of counterproductive information.

PMID- 24575887
TI  - Selective reactivity of monochloramine with extracellular matrix components
      affects the disinfection of biofilm and detached clusters.
AB  - The efficiency of monochloramine disinfection was dependent on the quantity and
      composition of extracellular polymeric substances (EPS) in biofilms, as
      monochloramine has a selective reactivity with proteins over polysaccharides.
      Biofilms with protein-based (Pseudomonas putida) and polysaccharide based EPS
      (Pseudomonas aeruginosa), as well as biofilms with varied amount of
      polysaccharide EPS (wild-type and mutant P. aeruginosa), were compared. The
      different reactivity of EPS components with monochloramine influenced
      disinfectant penetration, biofilm inactivation, as well as the viability of
      detached clusters. Monochloramine transport profiling measured by a chloramine
      sensitive microelectrode revealed a broader diffusion boundary layer between bulk
      and biofilm surface in the P. putida biofilm compared to those of P. aeruginosa
      biofilms. The reaction with proteins in P. putida EPS multiplied both the time
      and the monochloramine mass required to achieve a full biofilm penetration. Cell
      viability in biofilms was also spatially influenced by monochloramine diffusion
      and reaction within biofilms, showing a lower survival in the surface section and
      a higher persistence in the middle section of the P. putida biofilm compared to
      the P. aeruginosa biofilms. While polysaccharide EPS promoted biofilm cell
      viability by obstructing monochloramine reactive sites on bacterial cells,
      protein EPS hindered monochloramine penetration by reacting with monochloramine
      and reduced its concentration within biofilms. Furthermore, the persistence of
      bacterial cells detached from biofilm (over 70% for P. putida and ~40% for
      polysaccharide producing P. aeruginosa) suggested that currently recommended
      monochloramine residual levels may underestimate the risk of water quality
      deterioration caused by biofilm detachment. 

PMID- 24575888
TI  - Asymmetric synthesis of the HMG-CoA reductase inhibitor atorvastatin calcium: an
      organocatalytic anhydride desymmetrization and cyanide-free side chain elongation
      approach.
AB  - An efficient asymmetric synthesis of atorvastatin calcium has been achieved from
      commercially available diethyl 3-hydroxyglutarate through a novel approach that
      involves an organocatalytic enantioselective cyclic anhydride desymmetrization to
      establish C(3) stereogenicity and cyanide-free assembly of C7 amino type side
      chain via C5+C2 strategy as the key transformations. 

PMID- 24575889
TI  - Hit the mark with diffusion-weighted imaging: metastases of rhabdomyosarcoma to
      the extraocular eye muscles.
AB  - BACKGROUND: Rhabdomyosarcoma is the most frequent malignant intraorbital tumour
      in paediatric patients. Differentiation of tumour recurrence or metastases from
      post-therapeutic signal alteration can be challenging, using standard MR imaging
      techniques. Diffusion-weighted MRI (DWI) is increasingly considered a helpful
      supplementary imaging tool for differentiation of orbital masses. CASE
      PRESENTATION: We report on a 15-year-old female adolescent of Caucasian ethnicity
      who developed isolated bilateral thickening of extraocular eye muscles about two
      years after successful multimodal treatment of orbital alveolar rhabdomyosarcoma.
      Intramuscular restricted diffusion was the first diagnostic indicator suggestive
      of metastatic disease to the eye muscles. DWI subsequently showed signal changes
      consistent with tumour progression, complete remission under chemoradiotherapy
      and tumour recurrence. CONCLUSIONS: Restricted diffusivity is a strong early
      indicator of malignancy in orbital tumours. DWI can be the key to correct
      diagnosis in unusual tumour manifestations and can provide additional diagnostic
      information beyond standard MRI and PET/CT. Diffusion-weighted MRI is useful for
      monitoring therapy response and for detecting tumour recurrence.

PMID- 24575890
TI  - Metabolic engineering for p-coumaryl alcohol production in Escherichia coli by
      introducing an artificial phenylpropanoid pathway.
AB  - The plant polymer lignin is the greatest source of aromatic chemical structures
      on earth. Hence, the chemically diverse lignin monomers are valuable raw
      materials for fine chemicals, materials synthesis, and food and flavor
      industries. However, extensive use of this natural resource is hampered by the
      large number of different lignin monomers and the complex and irregular structure
      of lignin, which renders current processes for its chemical or enzymatic
      degradation inefficient. The microbial production of lignin monomers from
      renewable resources represents a promising alternative to lignin degradation,
      which could meet the demand for aromatic chemical structures. In this study, we
      describe the functional introduction of an artificial phenylpropanoid pathway
      into Escherichia coli, achieved by transferring several genes from plants and
      microbes. The established chimeric pathway efficiently converts l-tyrosine into
      the lignin precursor molecule p-coumaryl alcohol. 

PMID- 24575891
TI  - Switching of biologic disease modifying anti-rheumatic drugs in patients with
      rheumatoid arthritis in a real world setting.
AB  - OBJECTIVES: This study examined total healthcare costs and rates of patients with
      rheumatoid arthritis (RA) who switch biologic disease-modifying anti-rheumatic
      drug (bDMARD) therapy in a real world setting. METHODS: A retrospective
      longitudinal analysis was conducted in patients with RA using IMS PharMetrics
      Plus database from 1/1/2004 to 3/31/2010. The first-line cohort included patients
      newly initiated on abatacept or the tumor necrosis factor-alpha inhibitors (anti
      TNFs) adalimumab, etanercept, or infliximab, with 12 months of continuous follow
      up. The second-line cohort included patients initiating a bDMARD with evidence of
      a different bDMARD within the previous 2 years and with 12 months of continuous
      follow-up. Switching was defined as a different bDMARD claim within a 200% gap in
      days supply from the previous bDMARD claim. Non-switchers stayed on their bDMARD
      in the follow-up period. Monthly total healthcare costs for switchers and non
      switchers and rates of bDMARD switching were examined. Switch rates for each
      bDMARD were also compared. RESULTS: First-line switchers had significantly higher
      monthly total healthcare costs after the switch than non-switchers ($3759 vs
      $2343; p < 0.05), as did second-line switchers ($3956 vs $2616; p < 0.05). First
      line abatacept (2.1%) had significantly lower rates of switching compared to
      adalimumab (9.5%), etanercept (9.0%), and infliximab (5.5%). Second-line
      abatacept (8.0%) had significantly lower rates of switching compared to
      adalimumab (16.7%), etanercept (14.4%), and infliximab (14.3%). LIMITATIONS:
      There are no clinical data available in this database and, therefore, this study
      did not examine the clinical drivers of healthcare costs and switch rates.
      CONCLUSIONS: Monthly total healthcare costs were higher for bDMARD switchers
      following the switch compared to non-switchers. Patients on abatacept switched
      less frequently than patients on anti-TNFs. This study highlights the need to
      identify patients who are likely to switch in order to ensure they receive the
      appropriate therapy which may improve outcomes and decrease healthcare costs.

PMID- 24575892
TI  - Enzyme-labeled Pt@BSA nanocomposite as a facile electrochemical biosensing
      interface for sensitive glucose determination.
AB  - Electrocatalytic reactions of glucose oxidation based on enzyme-labeled
      electrochemical biosensors demand a high enzymatic activity and fast electron
      transfer property to produce the amplified signal response. Through a "green"
      synthesis method, Pt@BSA nanocomposite was prepared as a biosensing interface for
      the first time. Herein we presented a convenient and effective glucose sensing
      matrix based on Pt@BSA nanocomposite along with the covalent adsorption of
      glucose oxidase (GOD). The electrocatalytic activity toward oxygen reduction was
      significantly enhanced due to the excellent bioactivity of anchored GOD and
      superior catalytic performance of interior platinum nanoparticles, which was
      gradually restrained with the addition of glucose. A sensitive glucose biosensor
      was then successfully developed upon the restrained oxygen reduction peak
      current. Differential pulse voltammetry (DPV) was employed to investigate the
      determination performance of the enzyme biosensor, resulting in a linear response
      range from 0.05 to 12.05 mM with an optimal detection limit of 0.015 mM. The as
      proposed sensing technique revealed high selectivity against endogenous
      interfering species, satisfactory storage stability, acceptable durability, and
      favorable fabrication reproducibility with the RSD of 3.8%. During the practical
      application in human blood serum samples, this glucose biosensor obtained a good
      detection accuracy of analytical recoveries within 97.5 to 104.0%, providing an
      alternative scheme for glucose level assay in clinical application. 

PMID- 24575893
TI  - Controlled nucleation and growth of DNA tile arrays within prescribed DNA origami
      frames and their dynamics.
AB  - Controlled nucleation of nanoscale building blocks by geometrically defined seeds
      implanted in DNA nanoscaffolds represents a unique strategy to study and
      understand the dynamic processes of molecular self-assembly. Here we utilize a
      two-dimensional DNA origami frame with a hollow interior and selectively
      positioned DNA hybridization seeds to control the self-assembly of DNA tile
      building blocks, where the small DNA tiles are directed to fill the interior of
      the frame through prescribed sticky end interactions. This design facilitates the
      construction of DNA origami/array hybrids that adopt the overall shape and
      dimensions of the origami frame, forming a 2D array in the core consisting of a
      large number of simple repeating DNA tiles. The formation of the origami/array
      hybrid was characterized with atomic force microscopy, and the nucleation
      dynamics were monitored by serial AFM scanning and fluorescence spectroscopy,
      which revealed faster kinetics of growth within the frame as compared to growth
      without the presence of a frame. Our study provides insight into the fundamental
      behavior of DNA-based self-assembling systems. 

PMID- 24575894
TI  - Diversity of human lip prints: a collaborative study of ethnically distinct world
      populations.
AB  - BACKGROUND: Cheiloscopy is a comparatively recent counterpart to the long
      established dactyloscopic studies. Ethnic variability of these lip groove
      patterns has not yet been explored. AIM: This study was a collaborative effort
      aimed at establishing cheiloscopic variations amongst modern human populations
      from four geographically and culturally far removed nations: India, Saudi Arabia,
      Spain and Nigeria. SUBJECTS AND METHODS: Lip prints from a total of 754 subjects
      were collected and each was divided into four equal quadrants. The patterns were
      classified into six regular types (A-F), while some patterns which could not be
      fitted into the regular ones were segregated into G groups (G-0, G-1, G-2).
      Furthermore, co-dominance of more than one pattern type in a single quadrant
      forced us to identify the combination (COM, G-COM) patterns. RESULTS AND
      CONCLUSION: The remarkable feature noted after compilation of the data included
      pattern C (a bifurcate/branched prototype extending the entire height of the lip)
      being a frequent feature of the lips of all the populations studied, save for the
      Nigerian population in which it was completely absent and which showed a tendency
      for pattern A (a vertical linear groove) and a significantly higher
      susceptibility for combination (COM) patterns. Chi-square test and correspondence
      analysis applied to the frequency of patterns appearing in the defined
      topographical areas indicated a significant variation for the populations
      studied.

PMID- 24575896
TI  - Contribution of cytochrome P450 and UDT-glucuronosyltransferase to the metabolism
      of drugs containing carboxylic acid groups: risk assessment of acylglucuronides
      using human hepatocytes.
AB  - 1. In order to evaluate the inhibition activity of 1-aminobenzotriazole (ABT) and
      (-)-borneol (borneol) against cytochrome P450 (CYP) and UDP
      glucuronosyltransferase (UGT), the substrates of these metabolic enzymes were
      incubated with ABT and borneol in human hepatocytes. We found that 3 mM ABT and
      300 MUM borneol were the most suitable experimental levels to specifically
      inhibit CYP and UGT. 2. Montelukast, mefenamic acid, flufenamic acid, diclofenac,
      tienilic acid, gemfibrozil, ibufenac and repaglinide were markedly metabolized in
      human hepatocytes, and the metabolism of gemfibrozil, mefenamic acid and
      flufenamic acid was inhibited by borneol. With regard to repaglinide,
      montelukast, diclofenac and tienilic acid, metabolism was inhibited by ABT.
      Ibufenac was partly inhibited by both inhibitors. Zomepirac, tolmetin, ibuprofen,
      indomethacin and levofloxacin were moderately metabolized by human hepatocytes,
      and the metabolism of zomepirac, ibuprofen and indomethacin was equally inhibited
      by both ABT and borneol. The metabolism of tolmetin was strongly inhibited by
      ABT, and was also inhibited weakly by borneol. Residual drugs, telmisartan,
      valsartan, furosemide, naproxen and probenecid were scarcely metabolized. 3.
      Although we attempted to predict the toxicological risks of drugs containing
      carboxylic groups from the combination chemical stability and CLint via UGT, the
      results indicated that this combination was not sufficient and that clinical
      daily dose is important.

PMID- 24575897
TI  - Clinical relevance and cellular source of elevated soluble urokinase plasminogen
      activator receptor (suPAR) in acute liver failure.
AB  - BACKGROUND & AIMS: Acute liver failure (ALF) is a life-threatening condition with
      a high mortality rate. The expression of urokinase plasminogen activator receptor
      (uPAR, CD87) and release of its shedded receptor into serum as soluble uPAR
      (suPAR) have been closely related to immune activation and prognosis in systemic
      inflammation and cirrhosis. We now aimed at investigating the clinical relevance
      and cellular source of uPAR and circulating suPAR in ALF. METHODS: Serum suPAR
      concentrations were measured in 48 ALF patients and 62 healthy controls from a
      German liver transplantation centre. Hepatic immune cell subsets and uPAR
      expression were studied by FACS, qPCR and immunohistochemistry. RESULTS:
      Circulating suPAR levels were significantly increased in ALF patients,
      independent from the underlying aetiology, in comparison to controls. Serum suPAR
      concentrations were closely correlated with parameters reflecting liver cell
      injury, decreased liver function and the model of end-stage liver disease (MELD)
      score in ALF patients. By immunohistochemistry from explanted livers, ALF was
      associated with distinct immune cell accumulation and strong up-regulation of
      intrahepatic uPAR mRNA expression. CD87 (uPAR) expression was specifically
      detected on intrahepatic 'non-classical' monocytes (CD14(+) CD16(+) ), NKT and
      CD56(dim) NK cells isolated from human liver, but not on parenchymal or other non
      parenchymal hepatic cell types. Membrane-bound uPAR was rapidly cleaved from
      monocytes upon inflammatory stimulation by lipopolysaccharide (LPS) and partially
      by co-cultured lymphocytes. CONCLUSIONS: Similar to its prognostic properties in
      patients with sepsis or cirrhosis, intrahepatic uPAR activation and serum suPAR
      concentrations might serve as an interesting biomarker in ALF.

PMID- 24575898
TI  - Widespread epidemic cholera caused by a restricted subset of Vibrio cholerae
      clones.
AB  - Since 1817, seven cholera pandemics have plagued humankind. As the causative
      agent, Vibrio cholerae, is autochthonous in the aquatic ecosystem and some
      studies have revealed links between outbreaks and fluctuations in climatic and
      aquatic conditions, it has been widely assumed that cholera epidemics are
      triggered by environmental factors that promote the growth of local bacterial
      reservoirs. However, mounting epidemiological findings and genome sequence
      analysis of clinical isolates have indicated that epidemics are largely
      unassociated with most of the V. cholerae strains in aquatic ecosystems. Instead,
      only a specific subset of V. cholerae El Tor 'types' appears to be responsible
      for current epidemics. A recent report examining the evolution of a variety of V.
      cholerae strains indicates that the current pandemic is monophyletic and
      originated from a single ancestral clone that has spread globally in successive
      waves. In this review, we examine the clonal nature of the disease, with the
      example of the recent history of cholera in the Americas. Epidemiological data
      and genome sequence-based analysis of V. cholerae isolates demonstrate that the
      cholera epidemics of the 1990s in South America were triggered by the importation
      of a pathogenic V. cholerae strain that gradually spread throughout the region
      until local outbreaks ceased in 2001. Latin America remained almost unaffected by
      the disease until a new toxigenic V. cholerae clone was imported into Haiti in
      2010. Overall, cholera appears to be largely caused by a subset of specific V.
      cholerae clones rather than by the vast diversity of V. cholerae strains in the
      environment.

PMID- 24575895
TI  - Vaccines for Pseudomonas aeruginosa: a long and winding road.
AB  - Despite the recognition of Pseudomonas aeruginosa as an opportunistic pathogen,
      no vaccine against this bacteria has come to market. This review describes the
      current state-of-the-art in vaccinology for this bacterium. This includes a
      discussion of those at risk for infection, the types of vaccines and the
      approaches for empirical and targeted antigen selection under development, as
      well as a perspective on where the field should go. In addition, the challenges
      in developing a vaccine for those individuals at risk are discussed. 

PMID- 24575899
TI  - Can goal setting be isolated from activity-focused intervention in cerebral
      palsy?

PMID- 24575900
TI  - Uterine artery pseudoaneurysm manifesting at the time of evacuation for abortion:
      pseudoaneurysm without preceding events.

PMID- 24575902
TI  - Graphene phosphonic acid as an efficient flame retardant.
AB  - We report the preparation of graphene phosphonic acid (GPA) via a simple and
      versatile method and its use as an efficient flame retardant. In order to
      covalently attach phosphorus to the edges of graphene nanoplatelets, graphite was
      ball-milled with red phosphorus. The cleavage of graphitic C-C bonds during
      mechanochemical ball-milling generates reactive carbon species, which react with
      phosphorus in a sealed ball-mill crusher to form graphene phosphorus. Subsequent
      opening of the crusher in air moisture leads to violent oxidation of graphene
      phosphorus into GPA (highest oxidation state). The GPA is readily dispersible in
      many polar solvents, including neutral water, allowing for solution (spray)
      coating for high-performance, nontoxic flame-retardant applications. 

PMID- 24575903
TI  - Mycosis fungoides: an important differential diagnosis for acquired palmoplantar
      keratoderma.
AB  - Mycosis fungoides is the most common subtype of primary cutaneous lymphoma and
      has several clinical variants. We report a 74-year-old man presenting with an
      acquired palmoplantar keratoderma initially diagnosed and treated as psoriasis
      with suboptimal improvement. Several months later the patient developed patches
      and plaques that were histologically consistent with mycosis fungoides. These
      lesions were ameliorated with the treatment of the underlying mycosis fungoides
      and the palmoplantar keratoderma resolved promptly with radiotherapy. This case
      highlights the importance of considering mycosis fungoides as an infrequent but
      serious cause of acquired palmoplantar keratoderma. 

PMID- 24575904
TI  - Transference as a therapeutic instrument.

PMID- 24575905
TI  - Commentary on "Transference as a therapeutic instrument": Thinking about
      transference.

PMID- 24575906
TI  - Commentary on "Transference as a therapeutic instrument": What is transferred in
      transference?

PMID- 24575907
TI  - Commentary on "Transference as a therapeutic instrument": Transference then and
      now.

PMID- 24575908
TI  - Commentary on "Transference as a therapeutic instrument": Clara Thompson: a
      significant but forgotten voice from the past.

PMID- 24575909
TI  - Commentary on "Transference as a Therapeutic Instrument": Remembering Sullivan's
      psychoanalyst.

PMID- 24575910
TI  - Commentary on "Transference as a therapeutic instrument": Transference in plain
      old therapy.

PMID- 24575911
TI  - Commentary on "Transference as a therapeutic instrument": Foreseeing the real
      relationship.

PMID- 24575912
TI  - Differences and similarities between functional and personal recovery in an Asian
      population: a cluster analytic approach.
AB  - This study gathers empirical data to test whether two forms of recovery are
      related: (1) the traditional outcome-based notion of recovery from a mental
      illness, which is called "functional recovery," and (2) the more recent, consumer
      based concept of recovery in mental illness, which is called "personal recovery."
      A total of 150 Chinese outpatients were recruited, 75 with bipolar disorder and
      75 with schizophrenia, as determined by structured clinical interview.
      Participants were reported to be in clinical remission for at least the previous
      6 months by treating psychiatrists. Personal recovery was measured with the
      Stages of Recovery Scale, and functional recovery was measured with residential
      and employment status. In addition to clinical and demographic data, self-report
      measures included functioning (confirmed through chart review) and a survey of
      the participant's assessment of the importance of various elements of recovery.
      Personal recovery was significantly correlated with functional recovery; small
      effect size suggested that the two domains are far from identical. The strength
      of this correlation was stronger for participants with schizophrenia than for
      those with bipolar disorder. A cluster analysis also suggested that residential
      and employment statuses, along with personal recovery scores, were useful in
      differentiating participants. Patients were more likely to reach better recovery
      outcomes if they were female, married, had higher family income, and perceived
      social roles as less important to their recovery. Consistent with the consumer
      literature, personal recovery is related but still distinct from functional
      recovery. Personal recovery has more to do with life circumstances than with
      functioning status alone. 

PMID- 24575913
TI  - Objective and subjective olfaction across the schizophrenia spectrum.
AB  - Much research indicates that patients with schizophrenia have impaired olfaction
      detection ability. However, studies of individuals with psychometrically defined
      schizotypy reveal mixed results-some document impairments while others do not. In
      addition to deficits in objective accuracy in olfaction for patients with
      schizophrenia, there has been an interest in subjective experience of olfaction.
      Unfortunately, methods of assessing accuracy and subjective hedonic olfactory
      evaluations in prior studies may not have been sensitive enough to detect group
      differences in this area. This study employed a measure of olfactory functioning
      featuring an expanded scoring system to assess both accuracy and subjective
      evaluations of pleasant and unpleasant experience. Data were collected for
      patients with schizophrenia, young adults with psychometrically defined
      schizotypy, psychiatric outpatients, and healthy controls. Results of this study
      indicate that both the schizophrenia and outpatient psychiatric groups showed
      similar levels of impaired olfaction ability; however, the schizotypy group was
      not impaired in olfaction detection. Interestingly, with regard to subjective
      hedonic evaluation, it was found that patients with schizophrenia did not differ
      from psychiatric outpatients, whereas individuals with schizotypy tended to rate
      smells as significantly less pleasant than healthy control participants. This
      suggests that subjective olfactory assessment is abnormal in some manner in
      schizotypy. It also suggests that accuracy of olfaction identification may be a
      characteristic of severe mental illness across severe mental illness diagnoses.
      The results are potentially important for understanding olfaction deficits across
      the mental illness spectrum. 

PMID- 24575914
TI  - Perfectionism and interpersonal orientations in depression: an analysis of
      validation seeking and rejection sensitivity in a community sample of young
      adults.
AB  - The current study was conducted to uniquely investigate the associations among
      trait perfectionism, perfectionistic self-presentation, validation seeking,
      rejection sensitivity, and depression in a community sample. The authors' primary
      purpose was to focus on interpersonal orientations as sources of vulnerability
      that could potentially account for when perfectionism is dysfunctional. A sample
      of 183 young adults from a community sample completed the Multidimensional
      Perfectionism Scale, the Perfectionistic Self-Presentation Scale, and measures of
      growth seeking, validation seeking, rejection sensitivity, and depressive
      symptoms. Analyses confirmed that validation seeking was associated positively
      with all of the perfectionism measures with particularly strong associations
      between validation seeking and perfectionistic self-presentation. As expected,
      socially prescribed perfectionism and perfectionistic self-presentation had
      positive associations with rejection sensitivity. Further analyses established
      that the associations between interpersonal perfectionism and depressive symptoms
      were mediated by validation seeking, and socially prescribed perfectionism
      interacted with high rejection sensitivity to predict higher depressive symptoms.
      Overall, findings indicate that perfectionists are ego-involved individuals who
      strive for perfection as a means of proving themselves, and they are
      hypersensitive to interpersonal cues indicating failure and lack of acceptance
      from others. 

PMID- 24575916
TI  - Video conferencing technology in research on schizophrenia: a qualitative study
      of site research staff.
AB  - The objective of this study was to advance knowledge of the experience of
      multisite research staff with video conferencing mental health data collection
      among study participants with schizophrenia. An end-of-study focus group was
      conducted with all (N = 19) study coordinators of a multisite randomized trial of
      pharmacotherapy for schizophrenia to characterize the experiences of coordinators
      overseeing semistructured assessments via video conferencing technology (VCT).
      Researchers conducted an audiotaped voluntary focus group. Investigators
      independently coded a transcript of the focus group, followed by discussions to
      reach consensus on key themes. Three key themes emerged, involving issues
      associated with (a) the technology itself, (b) the technology in the context of
      clinical care and research, and (c) the feasibility of using VCT for study
      assessments, including coordinators' perceptions of participants' experience of
      VCT. Additional themes were that (a) interviewer skills appeared to moderate the
      impact of VCT, (b) research participants with serious psychiatric disorders who
      participated in VCT assessments appeared, overall, to be more amenable to the
      technology than research coordinators anticipated, and (c) because VCT will be
      adapted in a wide range of settings, staffing and resource needs should be
      considered in planning for and adopting VCT for psychiatric research or clinical
      assessment. This study adds contextual detail and emphasis to the existing
      literature on the use of VCT in research and factors regarding the effective
      deployment of the technology in research. 

PMID- 24575915
TI  - Rejection sensitivity and depression: mediation by stress generation.
AB  - Rejection sensitivity has been found to confer risk for depression. The process
      through which this occurs remains unclear. This risk factor also has been
      associated with negative behavioral tendencies and interpersonal difficulties.
      Drawing on these different lines of research, the current investigation aimed to
      evaluate stress generation, the tendency for depression-prone individuals to
      experience higher rates of life stressors that are at least in part influenced by
      their own behavior, as a potential mechanism mediating the link between rejection
      sensitivity and subsequent depressive symptoms. Sixty-six adults with a history
      of depression were followed over a 4-month interval and completed assessments of
      rejection sensitivity and depressive symptoms at baseline, and depressive
      symptoms, a diagnostic interview for depression, and a contextual threat life
      stress interview at 4-month follow-up. Consistent with the stress generation
      hypothesis, rejection sensitivity predicted higher rates of dependent stressors,
      but not independent ones, over the 4-month prospective follow-up period.
      Furthermore, prospectively occurring dependent stressors mediated the
      relationship between baseline rejection sensitivity and depressive symptoms at
      follow-up. The finding that stress generation may operate as a mediating
      mechanism underlying the pathway between rejection sensitivity and depression
      lends preliminary support for the importance of targeting maladaptive behavioral
      tendencies in rejection-sensitive individuals in clinical settings. 

PMID- 24575918
TI  - Effects of sea surface warming on marine plankton.
AB  - Ocean warming has been implicated in the observed decline of oceanic
      phytoplankton biomass. Some studies suggest a physical pathway of warming via
      stratification and nutrient flux, and others a biological effect on plankton
      metabolic rates; yet the relative strength and possible interaction of these
      mechanisms remains unknown. Here, we implement projections from a global
      circulation model in a mesocosm experiment to examine both mechanisms in a multi
      trophic plankton community. Warming treatments had positive direct effects on
      phytoplankton biomass, but these were overcompensated by the negative effects of
      decreased nutrient flux. Zooplankton switched from phytoplankton to grazing on
      ciliates. These results contrast with previous experiments under nutrient-replete
      conditions, where warming indirectly reduced phytoplankton biomass via increased
      zooplankton grazing. We conclude that the effect of ocean warming on marine
      plankton depends on the nutrient regime, and provide a mechanistic basis for
      understanding global change in marine ecosystems. 

PMID- 24575920
TI  - Two novel mutations affecting the same splice site of PKD1 correlate with
      different phenotypes in ADPKD.
AB  - Genetic heterogeneity is the main factor for significant variation in the course
      of autosomal dominant polycystic kidney disease (ADPKD). PKD1 patients have more
      severe renal outcomes compared with PKD2 patients. Co-inheritance of a mutation
      in both genes is associated with more severe phenotypes than that found with
      either mutation alone. However, the genotype-phenotype relationship is far from
      clear in ADPKD. Here, we observed two novel mutations, PKD1:c.12444G > A and
      PKD1:c.12444 + 1G > A, which alter the same splice donor site of intron 45,
      correlate with different renal outcomes. To explain the phenomenon, we analyzed
      the genic and allelic background of the patients, as well as the genetic
      modifiers, DKK3 and HNF-1beta as suggested. Only PKD1 variants were found, which
      highlights the allelic influence of PKD1 gene to be the last candidate factor.
      Segregation analysis, online mutation prediction, and recurrence mutation
      searching were applied to sort the variants. However, none of variants was found
      to be damaging or associated with the disease except PKD1:c.12444G > A and
      PKD1:c.12444 + 1G > A. Cloning and sequencing of the mutated cDNA sequences had
      shown unexpected different splicing effects caused by the mutations. PKD1:c.12444
      + 1G > A definitely destroyed the native splice site and created a novel donor
      site with truncating effect on PC1. In contrast, PKD1:c.12444G > A mainly
      weakened the site and decreased the expression of normal PC1. Since PC1
      negatively regulates cell proliferation in the process of cyst formation and
      enlargement, our observation may explain this new genotype-phenotype correlation
      and help to improve genetic counseling and diagnosis of the disease.

PMID- 24575921
TI  - Legislative reforms of the blood transfusion system in Pakistan.

PMID- 24575919
TI  - Health systems analysis of eye care services in Zambia: evaluating progress
      towards VISION 2020 goals.
AB  - BACKGROUND: VISION 2020 is a global initiative launched in 1999 to eliminate
      avoidable blindness by 2020. The objective of this study was to undertake a
      situation analysis of the Zambian eye health system and assess VISION 2020
      process indicators on human resources, equipment and infrastructure. METHODS: All
      eye health care providers were surveyed to determine location, financing sources,
      human resources and equipment. Key informants were interviewed regarding levels
      of service provision, management and leadership in the sector. Policy papers were
      reviewed. A health system dynamics framework was used to analyse findings.
      RESULTS: During 2011, 74 facilities provided eye care in Zambia; 39% were public,
      37% private for-profit and 24% owned by Non-Governmental Organizations. Private
      facilities were solely located in major cities. A total of 191 people worked in
      eye care; 18 of these were ophthalmologists and eight cataract surgeons,
      equivalent to 0.34 and 0.15 per 250,000 population, respectively. VISION 2020
      targets for inpatient beds and surgical theatres were met in six out of nine
      provinces, but human resources and spectacles manufacturing workshops were below
      target in every province. Inequalities in service provision between urban and
      rural areas were substantial. CONCLUSION: Shortage and maldistribution of human
      resources, lack of routine monitoring and inadequate financing mechanisms are the
      root causes of underperformance in the Zambian eye health system, which hinder
      the ability to achieve the VISION 2020 goals. We recommend that all VISION 2020
      process indicators are evaluated simultaneously as these are not individually
      useful for monitoring progress.

PMID- 24575924
TI  - Management of metastatic neck disease--summary of the 11th Evidence Based
      Management Day.

PMID- 24575925
TI  - Re: 12-minute consultation: an evidence-based approach to the management of
      dysphagia.

PMID- 24575926
TI  - Response to Puvanendran et al.

PMID- 24575927
TI  - Re: More codeine fatalities after tonsillectomy in North American children: time
      to revise prescribing practice!

PMID- 24575928
TI  - Response to Magos et al.

PMID- 24575929
TI  - A single-material method to create a nasal bolster.

PMID- 24575930
TI  - The use of a novel post-nasal space pack in routine nasal surgery.

PMID- 24575931
TI  - Thoracoscopic ligation of the thoracic duct complex in the treatment for high
      volume chyle leak following modified radical neck dissection: safe, feasible, but
      underutilised.

PMID- 24575932
TI  - Patient expectations in outpatient care.

PMID- 24575934
TI  - Texture analysis of cosmetic/pharmaceutical raw materials and formulations.
AB  - OBJECTIVES: The purpose of this work was to quantify textural properties of
      cosmetic and pharmaceutical raw materials. METHODS: Textural parameters such as
      hardness, consistency, cohesiveness, index of viscosity, stickiness and
      resilience were evaluated. The measurements were performed using texture analyser
      - a tensile metre equipped with special probes (in the form of acrylic cylinder
      and stainless steel sphere), which can penetrate the measured sample of a product
      recording the force, distance and time. The instrument simulates the action of a
      human finger touching the surface and probing the properties of an object. The
      set-up has been previously shown to quantify the rheological/textural properties
      of cosmetic and pharmaceutical products such as creams, lotion and gels as well
      as rheological behaviour of human skin. RESULTS AND CONCLUSIONS: The results
      include the analysis of water, glycerine and mineral oil as well as aqueous
      solutions of thickeners such as Acrylates/C10-30 Alkyl Acrylate Crosspolymer
      (Ultrez-20 obtained from Noveon) and carbomer. Solutions of common surfactants
      and complex surfactant formulations such as shampoos have also been investigated.
      The results, in the form plots of force as a function of time or distance,
      resulting from slow bidirectional probe movement (submergence and desubmergence)
      in the analysed fluid, were interpreted by considering buoyancy, drag and viscous
      drag force given by Stokes equation. The data can be used to correlate with
      tactile evaluations of products by trained panel evaluations.

PMID- 24575933
TI  - Associations between preterm birth, small-for-gestational age, and neonatal
      morbidity and cognitive function among school-age children in Nepal.
AB  - BACKGROUND: The long term consequences of low birth weight (LBW), preterm birth,
      small-for-gestational age (SGA, defined as birth weight for given gestational age
      less than the 10th percentile of the reference), and early newborn morbidity on
      functional outcomes are not well described in low income settings. METHODS: In
      rural Nepal, we conducted neurocognitive assessment of children (n = 1927) at 7-9
      y of age, for whom birth condition exposures were available. At follow-up they
      were tested on aspects of intellectual, executive, and motor function. RESULTS:
      The prevalence of LBW (39.6%), preterm birth (21.2%), and SGA (55.4%) was high,
      whereas symptoms of birth asphyxia and sepsis were reported in 6.7% and 9.1% of
      children. In multivariable regression analyses, adjusted for confounders, LBW was
      strongly associated with scores on the Universal Nonverbal Intelligence Test
      (UNIT), tests of executive function, and the Movement Assessment Battery for
      Children (MABC). Preterm was not associated with any of the test scores.
      Conversely, SGA was significantly (all p < 0.005) associated with lower UNIT
      scores (-2.04 SE = 0.39); higher proportion failure on Stroop test (0.06, SE =
      0.02); and lower scores on the backward digit span test (-0.16, SE = 0.04), MABC
      (0.98, SE = 0.25), and finger tapping test (-0.66, SE = 0.22) after adjusting for
      confounders. Head circumference at birth was strongly and significantly
      associated with all test scores. Neither birth asphyxia nor sepsis symptoms were
      significantly associated with scores on cognitive or motor tests. CONCLUSION: In
      this rural South Asian setting, intrauterine growth restriction is high and, may
      have a negative impact on long term cognitive, executive and motor function.

PMID- 24575935
TI  - Evaluating the role of nab-paclitaxel (Abraxane) in women with aggressive
      metastatic breast cancer.
AB  - Nab-paclitaxel (Abraxane((r))) is an albumin-bound form of paclitaxel that
      utilizes the natural properties of albumin to improve paclitaxel delivery to the
      tumor. It is licensed for use in metastatic breast cancer (MBC) at a dose of 260
      mg/m(2) Q3W based on its superior therapeutic index versus conventional
      paclitaxel 175 mg/m(2) Q3W demonstrated in a Phase III study. In a post-hoc
      analysis, nab-paclitaxel treatment was associated with rapid and dramatic tumor
      responses in patients with poor prognostic factors (visceral dominant disease,
      >=3 metastatic lesions), suggesting it may be a preferred treatment for these
      patients. Moreover, significant efficacy has been seen with nab-paclitaxel 100
      and 150 mg/m(2) QW 3/4, suggesting it may be possible to tailor use of this agent
      in the future. 

PMID- 24575936
TI  - Vascular events after transsylvian selective amygdalohippocampectomy and impact
      on epilepsy outcome.
AB  - OBJECTIVE: Epilepsy surgery is a standard treatment option for medically
      intractable temporal lobe epilepsy. Selective amygdalohippocampectomy (SAH) and
      anterior temporal lobectomy (ATL) are two of the standard surgical procedures in
      these cases. We conducted a retrospective analysis of patients treated with SAH
      via a modified transsylvian approach in our epilepsy center between 2008 and
      2011, and we analyzed the impact of adjacent procedure-related infarctions on
      seizure outcome in these patients. METHODS: Infarctions were detected by magnetic
      resonance imaging (MRI) within the first week postoperatively and by a second MRI
      9 months after surgical intervention. Neuropsychological testing was performed
      preoperatively. Evaluation of seizure outcome and postoperative
      neuropsychological testing were conducted approximately 1 year after epilepsy
      surgery. Correlative clinical data were analyzed by retrospective chart review.
      RESULTS: The postoperative MRI revealed temporal infarctions in 47.9% (n = 23/48)
      and frontal infarctions in 10.4% (n = 5/48) of the patients. These vascular
      events were asymptomatic in terms of focal neurologic deficits. Of the patients,
      68.5% (n = 37/54) were free of disabling seizures (Engel class I) 1 year after
      the procedure. Patients with temporal infarctions were significantly more often
      free of disabling seizures (Engel class I, p = 0.046) than patients without
      temporal infarctions. Neuropsychological testing indicated a deterioration in
      verbal memory after SAH in patients with infarctions on the language-lateralized
      hemisphere compared to patients without infarction (p = 0.011). All other tested
      neuropsychological categories showed no significant differences between patients
      with or without infarctions. SIGNIFICANCE: Our results indicate a surprisingly
      high number of procedure-related temporal infarctions after transsylvian SAH.
      Hence, the volume of nonfunctional "eliminated" tissue is enlarged
      unintentionally, which is a possible explanation for better seizure outcome in
      these patients. This result supports the notion that ATL is the favorable
      procedure for temporal lobe epilepsy compared to SAH in the nondominant
      hemisphere, as neuropsychological deficits are rarely to be expected.

PMID- 24575937
TI  - One-step synthesis of highly efficient nanocatalysts on the supports with
      hierarchical pores using porous ionic liquid-water gel.
AB  - Stable porous ionic liquid-water gel induced by inorganic salts was created for
      the first time. The porous gel was used to develop a one-step method to
      synthesize supported metal nanocatalysts. Au/SiO2, Ru/SiO2, Pd/Cu(2-pymo)2 metal
      organic framework (Cu-MOF), and Au/polyacrylamide (PAM) were synthesized, in
      which the supports had hierarchical meso- and macropores, the size of the metal
      nanocatalysts could be very small (<1 nm), and the size distribution was very
      narrow even when the metal loading amount was as high as 8 wt %. The catalysts
      were extremely active, selective, and stable for oxidative esterification of
      benzyl alcohol to methyl benzoate, benzene hydrogenation to cyclohexane, and
      oxidation of benzyl alcohol to benzaldehyde because they combined the advantages
      of the nanocatalysts of small size and hierarchical porosity of the supports. In
      addition, this method is very simple. 

PMID- 24575938
TI  - A chimeric protein encompassing hepatitis C virus epitopes is able to elicit both
      humoral and cell-mediated immune responses in mice.
AB  - Hepatitis C virus (HCV) infection is a worldwide health problem. Vaccines against
      this pathogen are not available and advances in this field are limited because of
      the high genetic variability of the virus, inaccessibility of animal models, and
      incomplete definition of immunological correlates of protection. In the present
      work, a chimeric protein, Eq1, encompassing HCV amino acid regions from
      structural antigens, was generated. Eq1 was expressed in GC-366 bacterial cells.
      After cell disruption, Eq1 was purified from the insoluble fraction by sequential
      steps of differential solubilization and metal chelating affinity chromatography.
      Eq1 was specifically recognized by anti-HCV positive human sera. Moreover,
      immunization of BALB/c mice with different doses of Eq1 formulated either in Alum
      or Freund's incomplete adjuvant elicited both humoral- and cellular-specific
      immune responses. Doses of 20 ug of Eq1 induced the strongest cell-mediated
      immune responses and only the formulation of this dose in Alum elicited a
      neutralizing antibody response against heterologous cell culture HCV. All these
      data together indicate that Eq1 is immunogenic in mice and might be an
      interesting component of vaccine candidates against HCV infection. 

PMID- 24575939
TI  - Prevalence of photosensitivity in chronic hepatitis C virus patients and its
      relation to serum and urinary porphyrins.
AB  - BACKGROUND & AIMS: HCV is a major cause of chronic liver disease in Egypt. The
      aim was to study the prevalence of photosensitivity among asymptomatic HCV
      infected patients and its possible relation to porphyrins levels and whether it
      can be considered an alarm for early diagnosis of the disease, which is the most
      important goal in the management. METHODS: This study included 100 accidentally
      discovered HCV positive cases and 100 HCV negative healthy controls. All patients
      and controls were subjected to: Detailed history and clinical examination,
      dermatological examination including evaluation of reaction to solar exposure,
      measurement of serum AST, ALT, albumin, bilirubin, serum and urinary porphyrins
      levels. RESULTS: The prevalence of photosensitivity among HCV-positive cases
      (33%) was significantly higher compared to 10% in the control group. Serum
      porphyrins were positive in 46 cases (46%), twenty-three cases (23%) had positive
      urinary porphyrins, while only four controls (4%) showed positive serum
      porphyrins and one (1%) showed positive urinary porphyrins, the difference was
      statistically significant. Cases with photosensitivity showed significantly
      higher prevalence of serum and urinary porphyrins existence as well as serum
      porphyrins levels. Levels of viraemia showed statistically significant relation
      to levels of porphyrins. CONCLUSION: Asymptomatic chronic HCV infection cases
      showed significantly high prevalence of photosensitivity, which is related to the
      associated disturbance of porphyrins metabolism. Photosensitivity can thus be
      considered an early marker of HCV infection. Patients discovered to have recently
      acquired photosensitivity should be screened for HCV infection especially in
      endemic areas like Egypt.

PMID- 24575940
TI  - Molecular dynamics study of nanoconfined water flow driven by rotating electric
      fields under realistic experimental conditions.
AB  - In our recent work, J. Chem. Phys. 2013, 138, 154712, we demonstrated the
      feasibility of unidirectional pumping of water, exploiting translational
      rotational momentum coupling using nonequilibrium molecular dynamics simulations.
      Flow can be sustained when the fluid is driven out of equilibrium by an external
      spatially uniform rotating electric field and confined between two planar
      surfaces exposing different degrees of hydrophobicity. The permanent dipole
      moment of water follows the rotating field, thus inducing the molecules to spin,
      and the torque exerted by the field is continuously injected into the fluid,
      enabling a steady conversion of spin angular momentum into linear momentum. The
      translational-rotational coupling is a sensitive function of the rotating
      electric field parameters. In this work, we have found that there exists a small
      energy dissipation region attainable when the frequency of the rotating electric
      field matches the inverse of the dielectric relaxation time of water and when its
      amplitude lies in a range just before dielectric saturation effects take place.
      In this region, that is, when the frequency lies in a small window of the
      microwave region around ~20 GHz and amplitude ~0.03 V A(-1), the translational
      rotational coupling is most effective, yielding fluid velocities of magnitudes of
      ~2 ms(-1) with only moderate fluid heating. In this work, we also confine water
      to a realistic nanochannel made of graphene giving a hydrophobic surface on one
      side and beta-cristobalite giving a hydrophilic surface on the other, reproducing
      slip-and-stick velocity boundary conditions, respectively. This enables us to
      demonstrate that in a realistic environment, the coupling can be effectively
      exploited to achieve noncontact pumping of water at the nanoscale. A quantitative
      comparison between nonequilibrium molecular dynamics and analytical solutions of
      the extended Navier-Stokes equations, including an external rotating electric
      field has been performed, showing excellent agreement when the electric field
      parameters match the aforementioned small energy dissipation region. 

PMID- 24575941
TI  - A retrospective study to assess the epidemiological and economic burden of
      pneumococcal diseases in adults aged 50 years and older in Taiwan.
AB  - OBJECTIVE: Invasive pneumococcal disease (IPD) and pneumococcal pneumonia cause
      substantial morbidity and mortality worldwide. This retrospective study was
      conducted to estimate the disease burden from pneumococcal disease in older
      adults in Taiwan from a health insurer's perspective. METHODS: Data for the years
      2002-2009 from patients aged >=50 years with insurance records indicating
      pneumococcal meningitis, pneumococcal bacteremia, or hospitalized or outpatient
      pneumonia were obtained from the National Health Insurance Research Database in
      Taiwan. Admission data for inpatients, visit data for outpatients, and associated
      costs were extracted from the database to estimate the incidence, case fatality
      rates, and direct and indirect costs of pneumococcal disease episodes. These data
      were applied to the estimated population of Taiwan in 2010 to provide an
      estimated disease burden for a single year from the payer perspective. RESULTS:
      The average incidence per 100,000 person years was 2.4 for IPD, 278.8 for
      hospitalized pneumococcal pneumonia, and 1376.4 for outpatient pneumococcal
      pneumonia. The average case fatality rate was 12.3% for IPD and 10.0% for
      hospitalized pneumonia. Hospitalized pneumonia accounted for over 90% of direct
      medical costs. The incidence of hospitalized pneumococcal pneumonia per 100,000
      person years was 84.4 for adults of 50-64 years, 313.1 for adults of 65-74 years,
      820.3 for adults of 75-84 years, and 1650.9 for adults of 85+ year of age. In
      2010, it was estimated there were over 113,000 episodes of pneumococcal disease,
      causing almost 2000 deaths, with direct medical costs of more than NT$3.4 billion
      annually. CONCLUSIONS: Pneumococcal disease is a significant cause of mortality
      and excess healthcare expense among the elderly in Taiwan. Disease burden in
      older adults increases with advancing age.

PMID- 24575943
TI  - Rapid identification of group B streptococcus carriage by PCR to assist in the
      management of women with prelabour rupture of membranes in term pregnancy.
AB  - BACKGROUND: Management of prelabour rupture of membranes at term (37 weeks
      gestation or later) (TPROM) remains complicated in the absence of a rapid assay
      for group B streptococcus (GBS) colonisation. AIMS: To evaluate the accuracy and
      clinical utility of a commercial PCR assay, compared with culture, for detection
      of GBS colonisation in pregnant women presenting with TPROM. METHODS: A
      prospective study of women presenting with TPROM conducted in a large tertiary
      hospital (Westmead Hospital, Australia). Five hundred and seventy-four
      consecutive women with TPROM were enrolled between July 2006 and November 2007.
      Paired low vaginal and anal swabs were collected from women presenting with TPROM
      for PCR and culture on GBS selective agar following broth enrichment. Primary
      outcomes were sensitivity and specificity of PCR compared with GBS selective
      enrichment culture. Secondary analyses included comparison with a historical but
      otherwise similar cohort regarding clinical utility, maternal and neonatal
      outcomes. RESULTS: PCR sensitivity and specificity were 89.0% (95% CI - 82.8
      93.6%) and 97.9% (95% CI - 96.0-99.0%), respectively, compared with culture.
      72.3% of women were aware of their GBS PCR status within 3 h of presentation.
      Compared with the historical cohort, PCR reduced the requirement for intrapartum
      antibiotics by 25.6% (P < 0.001). There were no significant differences in
      maternal outcomes or combined rates of admissions to neonatal intensive care or
      special care nursery. CONCLUSIONS: Group B streptococcus PCR is an accurate,
      rapid, safe and practical alternative to culture for detection of GBS
      colonisation in pregnant women at the time of TPROM. This method has the
      potential advantage to reduce costs associated with length of hospital stay.

PMID- 24575942
TI  - Induction of social behavior in zebrafish: live versus computer animated fish as
      stimuli.
AB  - The zebrafish offers an excellent compromise between system complexity and
      practical simplicity and has been suggested as a translational research tool for
      the analysis of human brain disorders associated with abnormalities of social
      behavior. Unlike laboratory rodents zebrafish are diurnal, thus visual cues may
      be easily utilized in the analysis of their behavior and brain function. Visual
      cues, including the sight of conspecifics, have been employed to induce social
      behavior in zebrafish. However, the method of presentation of these cues and the
      question of whether computer animated images versus live stimulus fish have
      differential effects have not been systematically analyzed. Here, we compare the
      effects of five stimulus presentation types: live conspecifics in the
      experimental tank or outside the tank, playback of video-recorded live
      conspecifics, computer animated images of conspecifics presented by two software
      applications, the previously employed General Fish Animator, and a new
      application Zebrafish Presenter. We report that all stimuli were equally
      effective and induced a robust social response (shoaling) manifesting as reduced
      distance between stimulus and experimental fish. We conclude that presentation of
      live stimulus fish, or 3D images, is not required and 2D computer animated images
      are sufficient to induce robust and consistent social behavioral responses in
      zebrafish.

PMID- 24575944
TI  - 1-(N-acylamino)alkyl sulfones from N-acyl-alpha-amino acids or N-alkylamides.
AB  - A variety of N-(1-methoxyalkyl)amides or carbamates react readily with sodium
      aryl sulfinates in the presence of triphenylphosphonium tetrafluoroborate or
      bromide in CHCl3 under mild conditions to give 1-(N-acylamino)alkyl sulfones in
      good yields. A combination of this reaction with the recently described
      electrochemical decarboxylative alpha-methoxylation of N-acyl-alpha-amino acids
      to give N-(1-methoxyalkyl)amides in the presence of 3-(1-piperidino)propyl
      functionalized silica gel (SiO2-Pip) enables an effective two-pot transformation
      of N-acyl-alpha-amino acids to 1-(N-acylamino)alkyl sulfones. Alternatively, N-(1
      methoxyalkyl)amides can be obtained by electrochemical alpha-methoxylation of
      either N-alkylamides, lactams, or N-alkylcarbamates. 

PMID- 24575945
TI  - The effects of night duty, fatigue, and unskilled staff.

PMID- 24575946
TI  - Multilayer epitaxial growth of lead phthalocyanine and C(70) using CuBr as a
      templating layer for enhancing the efficiency of organic photovoltaic cells.
AB  - The molecular orientation and crystallinity of donor and acceptor molecules are
      important for high-efficiency organic photovoltaic cells (OPVs) because they
      significantly influence both the absorption of light and charge-transport
      characteristics. We report that the templating effect extends to multilayers to
      increase the crystallinity and to modify the orientation of the crystals of lead
      phthalocyanine (PbPc) and C70 layers at the same time by adopting CuBr as a new
      templating layer on indium tin oxide (ITO). The formation of a monoclinic phase
      with a preferred orientation of (320) for PbPc and a fcc phase with a preferred
      orientation of (220) for C70 on the PbPc layer is revealed by X-ray diffraction
      (XRD) patterns. The multilayer epitaxy results in an increase of the exciton
      diffusion lengths from 5.6 to 8.8 nm for PbPc and from 6.9 to 13.8 nm for C70 to
      enhance the power conversion efficiency (PCE) of the planar heterojunction OPVs
      composed of PbPc and C70 from 1.4 to 2.3%. The quasi-epitaxy model is proposed to
      explain the multilayer epitaxy. 

PMID- 24575947
TI  - Significance of hydrogen breath tests in children with suspected carbohydrate
      malabsorption.
AB  - BACKGROUND: Hydrogen breath tests are noninvasive procedures frequently applied
      in the diagnostic workup of functional gastrointestinal disorders. Here, we
      review hydrogen breath test results and the occurrence of lactose, fructose and
      sorbitol malabsorption in pediatric patients; and determine the significance of
      the findings and the outcome of patients with carbohydrate malabsorption.
      METHODS: We included 206 children (88 male, 118 female, median age 10.7 years,
      range 3-18 years) with a total of 449 hydrogen breath tests (lactose, n = 161;
      fructose, n = 142; sorbitol, n = 146) into a retrospective analysis. Apart from
      test results, we documented symptoms, the therapeutic consequences of the test,
      the outcome and the overall satisfaction of the patients and families. RESULTS:
      In total, 204 (46%) of all breath tests were positive. Long-term follow-up data
      could be collected from 118 patients. Of 79 patients (67%) who were put on a diet
      reduced in lactose, fructose and/or sorbitol, the majority (92%, n = 73) reported
      the diet to be strict and only 13% (n = 10) had no response to diet. Most
      families (96%, n = 113) were satisfied by the test and the therapy. There were
      only 21 tests (5%) with a borderline result because the criteria for a positive
      result were only partially met. CONCLUSIONS: Hydrogen breath tests can be helpful
      in the evaluation of children with gastrointestinal symptoms including functional
      intestinal disorders. If applied for a variety of carbohydrates but only where
      indicated, around two-third of all children have positive results. The
      therapeutic consequences are successfully relieving symptoms in the vast majority
      of patients.

PMID- 24575948
TI  - Hepatitis B reactivation in HBsAg-negative/HBcAb-positive allogeneic
      haematopoietic stem cell transplant recipients: risk factors and outcome.
AB  - HBsAg-negative/HBcAb-positive haematopoietic stem cell transplant (HSCT)
      recipients are at high risk of hepatitis B virus (HBV) reactivation. Allogeneic
      HSCT recipients from years 2000 to 2010 were evaluated in order to study the
      impact of being HBsAg-negative/HBcAb-positive in this population. Overall, 137 of
      764 patients (18%) were HBsAg-negative/HBcAb-positive before HSCT. Overall
      survival, non-relapse mortality (NRM), acute and chronic graft-vs.-host disease
      were similar in HBcAb-positive and HBcAb-negative patients. Reactivation occurred
      in 14 patients (10%) within a median of 19 months after HSCT (range 9-77). Cause
      specific hazard for reactivation was decreased in the case of an HBV
      immune/exposed donor (HRadjusted = 0.12; 95% CI, 0.02-0.96; p 0.045) and
      increased in patients who received rituximab treatment (HRadjusted = 2.91; 95%CI,
      0.77-10.97; p 0.11). Competing risk analyses documented a protective role of an
      HBV-immune/exposed donor (p 0.041) and an increased probability associated with
      the length of treatment with cyclosporine (p <0.001) and treatment with rituximab
      (but not with low-dose rituximab prophylaxis, p <0.001 at each landmark point).
      No differences in overall survival and NRM were found between patients with and
      without HBV reactivation. The donor's immunity was independently and consistently
      associated with a decreased risk of HBV reactivation, while rituximab and
      cyclosporine treatments increased the probability.

PMID- 24575951
TI  - Demonstrating the capability of the high-performance plasmonic gallium-graphene
      couple.
AB  - Metal nanoparticle (NP)-graphene multifunctional platforms are of great interest
      for exploring strong light-graphene interactions enhanced by plasmons and for
      improving performance of numerous applications, such as sensing and catalysis.
      These platforms can also be used to carry out fundamental studies on charge
      transfer, and the findings can lead to new strategies for doping graphene. There
      have been a large number of studies on noble metal Au-graphene and Ag-graphene
      platforms that have shown their potential for a number of applications. These
      studies have also highlighted some drawbacks that must be overcome to realize
      high performance. Here we demonstrate the promise of plasmonic gallium (Ga)
      nanoparticle (NP)-graphene hybrids as a means of modulating the graphene Fermi
      level, creating tunable localized surface plasmon resonances and, consequently,
      creating high-performance surface-enhanced Raman scattering (SERS) platforms.
      Four prominent peculiarities of Ga, differentiating it from the commonly used
      noble (gold and silver) metals are (1) the ability to create tunable (from the UV
      to the visible) plasmonic platforms, (2) its chemical stability leading to long
      lifetime plasmonic platforms, (3) its ability to n-type dope graphene, and (4)
      its weak chemical interaction with graphene, which preserves the integrity of the
      graphene lattice. As a result of these factors, a Ga NP-enhanced graphene Raman
      intensity effect has been observed. To further elucidate the roles of the
      electromagnetic enhancement (or plasmonic) mechanism in relation to electron
      transfer, we compare graphene-on-Ga NP and Ga NP-on-graphene SERS platforms using
      the cationic dye rhodamine B, a drug model biomolecule, as the analyte. 

PMID- 24575949
TI  - Kinesiologic taping reduces morbidity after oral and maxillofacial surgery: a
      pooled analysis.
AB  - BACKGROUND: Postoperative morbidity is a major disadvantage after oral and
      maxillofacial (OMF) surgery, often caused by pain, trismus and swelling affecting
      patients' quality of life. The goal of this study was to examine the effect of
      kinesiologic taping (KT) on swelling, pain, trismus and patients' satisfaction
      after OMF surgery. MATERIALS AND METHODS: Performing a pooled analysis of 96
      patients that were assigned for maxillofacial treatment (midface fractures n =
      30, mandibular fractures n = 26, wisdom tooth removal n = 40) divided into
      treatment either with or without kinesiologic tape application. Tape was applied
      directly after surgery and maintained for at least 5 d postoperatively. Facial
      swelling was quantified at six specific points in time using a five-line
      measurement. Pain and degree of mouth opening was measured. Patients' objective
      feeling and satisfaction was queried. RESULTS: Application of KT after OMF
      surgery has a significant influence on the reduction of swelling decreasing the
      turgidity for 60% during the first 2 d after surgery. Evaluating all patients
      swelling was significantly lower in the KT treatment group (T2: 63.5 cm +/- 4.3;
      T3: 62.5 cm +/- 4.2; T4: 61.6 cm +/- 4.2) than in the no-KT group (T2: 67.6 cm +/
      5.0; T3: 67.0 cm +/- 5.0; T4: 64.8 cm +/- 4.8) at T2 (p < 0.001), T3 (p <
      0.001), and T4 (p = 0.001). VAS Pain values were scored significantly lower for
      the KT group (T1: 2.5 +/- 2.0 (p = 0.006); T2: 1.7 +/- 2.0 (p < 0.001); T3: 1.5
      +/- 2.3 (p = 0.004); T4: 0.6 +/- 1.1 (p = 0.001) compared to the no-KT group (T1:
      3.8 +/- 2.5; T2: 3.5 +/- 2.7; T3: 2.9 +/- 2.2; T4: 1.6 +/- 1.7). A statistically
      significant amelioration in mean mouth opening ability was observed in the KT
      group (T1-BL: -0.08 cm +/- 0.49 (p = 0.025); T2-BL: 0.07 cm  +/- 0.59 (p =
      0.012); T3-BL: 0.20 +/- 0.63 (p = 0.013); T4-BL: 0.42 +/- 0.59 (p = 0.003))
      compared to the no-KT group (T1-BL: -0.47 cm +/- 0.86; T2-BL: -0.39 cm +/- 0.84;
      T3-BL: -0.24 +/- 0.89; T4-BL: -0.13 +/- 1.02). CONCLUSION: KT after OMF surgery
      is a promising, simple, less traumatic, economical approach free from systemic
      adverse reaction upgrading patients' quality of life.

PMID- 24575952
TI  - Biomechanical characteristics and reinsertion guidelines for retrieved
      orthodontic miniscrews.
AB  - OBJECTIVES: To analyze morphological variations of retrieved orthodontic
      miniscrews and to evaluate the mechanical properties that may adversely affect
      relocation of miniscrews. MATERIALS AND METHODS: Retrieved miniscrews were
      classified with scanning electron microscopy according to the degree of
      morphological deformation of the tip. To evaluate the differences in mechanical
      characteristics during reinsertion, changes in insertion torque, insertion time
      and differences in successful insertion load were compared between unused
      controls and retrieved miniscrews. In addition, surface composition analysis of
      retrieved miniscrews was performed using energy-dispersive x-ray spectroscopy.
      RESULTS: Significant tip deformation was evident in the majority (>84.5%) of
      retrieved miniscrews. Initial conditions such as insertion site or duration of
      insertion were not associated with the presence of tip deformation. Insertion
      load for successful bone penetration increased in proportion to the degree of tip
      deformation; however, serial changes in insertion torque were similar to those of
      the controls. Deposited debris such as carbon, calcium, and phosphorus was noted
      on the retrieved miniscrews. CONCLUSION: Miniscrews retrieved after primary
      insertion exhibited decreased cutting ability due to deformation of the tip
      structure, as well as surface contamination.

PMID- 24575953
TI  - Clinical status of Sagliker syndrome: a case report and literature review.
AB  - In a 53-year-old woman, Sagliker syndrome developed during 22 years of treatment
      with intermittent hemodialysis as a result of severe secondary
      hyperparathyroidism (SHPT) complicating end-stage renal disease. She failed
      medical managements and lost her renal graft just after the kidney
      transplantation due to acute rejection. Although surgical parathyroidectomy was
      effective, the parathyroid hormone level became extremely high again due to
      recurrent hyperparathyroidism. It is possible that such patient could survive
      long-term with dialysis, but prevention of severe SHPT is the most important.

PMID- 24575954
TI  - Sunlight inactivation of MS2 coliphage in the absence of photosensitizers:
      modeling the endogenous inactivation rate using a photoaction spectrum.
AB  - The endogenous sunlight inactivation rates of MS2 coliphage in photosensitizer
      free water were measured (kobs) under different light conditions and compared to
      modeled inactivation rates (kmod) computed using a previously published action
      spectrum. Experiments were conducted under simulated and natural sunlight. There
      was generally good agreement between modeled and observed MS2 sunlight
      inactivation rates in the summer and winter, suggesting that the action spectrum
      can be used to predict changes in the inactivation rate caused by diurnal and
      seasonal changes in natural sunlight irradiance. However, we show that a major
      source of uncertainty in the predictions is the ability to accurately measure or
      model the comparatively weak and highly variable solar irradiance between 280 and
      300 nm, a range to which the inactivation rate is very sensitive. The action
      spectrum was also used to predict the endogenous inactivation rates of MS2 at
      different depths in a column of strongly humic-colored [i.e., solar ultraviolet
      (UV)-attenuating] wetland water under simulated sunlight; we observed fairly good
      agreement between kobs and kmod, suggesting that the action spectrum can be used
      to estimate the decrease in the endogenous inactivation rate caused by spectrally
      selective sunlight attenuation in the water column. 

PMID- 24575955
TI  - Main barriers to effective implementation of stroke care pathways in France: a
      qualitative study.
AB  - BACKGROUND: Stroke Care Pathways (SCPs) aim to improve quality of care by
      providing better access to stroke units, rehabilitation centres, and home care
      for dependent patients. The objective of this study was to identify the main
      barriers to effective implementation of SCPs in France. METHODS: We selected 4
      types of SCPs currently implemented in France that differed in terms of
      geographical location, population size, socio-economic conditions, and available
      health care facilities. We carried out 51 semi-structured interviews of 44 key
      health professionals involved in these SCPs and used the interview data to (i)
      create a typology of the organisational barriers to effective SCP implementation
      by axial coding, (ii) define barrier contents by vertical coding. The typology
      was validated by a panel of 15 stroke care professionals. RESULTS: Four main
      barriers to effective SCP implementation were identified: lack of resources
      (31/44 interviewees), coordination problems among staff (14/44) and among
      facilities (27/44), suboptimal professional and organisational practices (16/44),
      and inadequate public education about stroke (13/44). Transposition of the
      findings onto a generic SCP highlighted alternative care options and identified
      10 to 17 barriers that could disrupt continuity of care. CONCLUSION: Lack of
      resources was considered to be the chief obstacle to effective SCP
      implementation. However, the main weakness of existing SCPs was poor
      communication and cooperation among health professionals and among facilities. We
      intend to use this knowledge to construct a robust set of quality indicators for
      use in SCP quality improvement initiatives, in comparisons between SCPs, and in
      the assessment of the effective implementation of clinical practice guidelines.

PMID- 24575957
TI  - Acetaminophen-induced liver injury in obesity and nonalcoholic fatty liver
      disease.
AB  - Although acetaminophen (APAP) is usually considered as a safe drug, this
      painkiller can lead to acute liver failure after overdoses. Moreover, there is
      evidence that the maximum recommended dosage can induce hepatic cytolysis in some
      individuals. Several predisposing factors appear to enhance the risk and severity
      of APAP-induced liver injury including chronic alcoholic liver disease and
      nonalcoholic fatty liver disease (NAFLD), which refers to a large spectrum of
      hepatic lesions linked to obesity. In contrast, obesity by itself does not seem
      to be associated with a higher risk of APAP-induced liver injury. Since 1987,
      seven studies dealt with APAP-induced hepatotoxicity in rodent models of NAFLD
      and five of them found that this liver disease was associated with higher APAP
      toxicity. Unfortunately, these studies did not unequivocally established the
      mechanism(s) whereby NAFLD could favour APAP hepatotoxicity, although some
      investigations suggested that pre-existent induction of hepatic cytochrome P450
      2E1 (CYP2E1) could play a significant role by increasing the generation of N
      acetyl-p-benzoquinone imine (NAPQI), the toxic metabolite of APAP. Moreover, pre
      existent mitochondrial dysfunction associated with NAFLD could also be involved.
      In contrast, some investigations suggested that factors that could reduce the
      risk and severity of APAP hepatotoxicity in obesity and NAFLD include higher
      hepatic APAP glucuronidation, reduced CYP3A4 activity and increased volume of
      body distribution. Thus, the occurrence and the outcome of APAP-induced liver
      injury in an obese individual with NAFLD might depend on a delicate balance
      between metabolic factors that can be protective and others that favour large
      hepatic levels of NAPQI. 

PMID- 24575958
TI  - Is routine chest X-ray after surgical and percutaneous tracheostomy necessary in
      adults: a systemic review of the current literature.
AB  - BACKGROUND: For many years, routine post-tracheostomy chest X-ray has been the
      standard of care for patients in many countries. However, recent evidence
      suggests that this is unnecessary and cost-ineffective. OBJECTIVE: To review the
      current literature and examine the role of routine post-tracheostomy chest X-ray
      in adult patients. TYPE OF REVIEW: Systemic review. SEARCH STRATEGY: Electronic
      databases (PubMed, EMBASE, Cochrane) were searched using the keywords 'chest X
      ray/radiography/radiograph' and 'tracheostomy/tracheotomy' in various
      permutations. Search period ranged from 1960 to 2012. Inclusion criteria included
      systematic reviews, meta-analyses, randomised control trials, prospective and
      retrospective case series. Paediatric and non-English articles were excluded.
      Abstracts and subsequently full text articles were screened by two of the authors
      independently. References from obtained articles were also examined. EVALUATION
      METHOD: Specific outcome measures were collated to evaluate the usefulness of
      post-tracheostomy chest X-ray: Chest X-ray detected (tracheostomy-related)
      complication rates Proportion of cases requiring significant intervention
      Potential predictors of complications RESULTS: Routine post-tracheostomy chest X
      ray is of a low yield, and its findings had limited impact on patient management.
      Complication detection rates for surgical and percutaneous tracheostomy are 2.2%
      and 3.2%, respectively. Only 0.7% and 1.8% of chest X-rays performed in surgical
      and percutaneous tracheostomy cases, respectively, required intervention. Certain
      groups of patients, however, are at higher risks of complications, and may
      benefit from post-tracheostomy chest X-ray. For surgical tracheostomy, these
      groups include those with post-operative signs and symptoms of complications or
      had emergent or 'difficult' tracheostomies. For percutaneous tracheostomy, high
      risk patients include trauma cases (unspecified), patients with post-procedural
      signs and symptoms of complications, patients who have high ventilatory
      requirements, difficult tracheostomy cases or tracheostomy cases performed
      without bronchoscopic guidance. CONCLUSION: The practice of routine post
      tracheostomy chest X-ray is debatable owing to its low yield and minimal impact
      on clinical management. However, certain groups of patients appear to be at
      higher risks of post-tracheostomy complications; currently, there is insufficient
      evidence to conclude the absolute need for routine chest X-ray in these groups of
      patients, although it may be prudent to do so based on available evidence in the
      literature and logical clinical reasoning.

PMID- 24575959
TI  - Breaking the data barrier in computational medicinal chemistry.

PMID- 24575960
TI  - Computational target fishing: what should chemogenomics researchers expect for
      the future of in silico drug design and discovery?

PMID- 24575961
TI  - The roles of computational chemistry in the ligand design of G protein-coupled
      receptors: how far have we come and what should we expect?

PMID- 24575956
TI  - Poor autonomic nervous system functioning during sleep in recently detoxified
      alcohol-dependent men and women.
AB  - BACKGROUND: Alcoholism is considered an important risk factor for cardiovascular
      (CV) disease. Autonomic nervous system (ANS) function is a major indicator of CV
      health. Sleep is a suitable model to investigate ANS activity free from wake
      related confounders. We investigated nighttime ANS functioning, and the relation
      between ANS activity and severity of alcohol dependence in chronic alcoholism.
      METHODS: Fourteen recently abstaining alcoholics (age: 42.0 +/- 9.0 years, 7
      women) and 16 age- and sex-matched controls (age: 45.2 +/- 9.1 years, 8 women)
      underwent a night of standard clinical polysomnography, including
      electrocardiographic recording. Time- and frequency-domain spectral analysis of
      heart rate variability (HRV) was performed across hours of the night and during
      artifact-free epochs of stable sleep and wakefulness (presleep wakefulness, rapid
      eye-movement [REM], and non-REM sleep). RESULTS: Alcoholics had a poorer
      subjective and objective sleep quality compared to controls. Across the night,
      alcoholic men and women had elevated heart rate, reduced total HRV, that is,
      lower standard deviation of normal-to-normal interbeat intervals, and reduced
      high frequency (HF) activity (assessed by the HF power and by the square root of
      the mean squared of successive heart period differences). This ANS pattern was
      most apparent at the beginning of the night. None of the ANS measures was
      associated with lifetime alcohol consumption or duration of alcohol dependence.
      CONCLUSIONS: Our results show that ANS functioning is disrupted during the night,
      even in undisturbed sleep periods, indicating poor CV functioning in recently
      detoxified alcohol-dependent men and women.

PMID- 24575962
TI  - Improving data mining strategies for drug design.

PMID- 24575964
TI  - Interview with Paul Selzer.
AB  - Paul Selzer, a computational chemist at Novartis (Basel, Switzerland), has been
      part of the computational medicinal chemistry field for over 20 years. Prior to
      joining Novartis in 1999, Selzer gained his PhD in computational chemistry from
      the University of Erlangen-Nuremberg (Erlangen, Germany) before working as a
      postdoctoral researcher. Selzer has authored a number of high-impact publications
      in the field and in this interview with Future Medicinal Chemistry, discusses
      some of the pressing issues in the computational medicinal chemistry arena,
      current work being conducted by the research group at Novartis, and more.
      Interview conducted by James Potticary, Assistant Commissioning Editor.

PMID- 24575965
TI  - Combinatorial chemistry by ant colony optimization.
AB  - BACKGROUND: Prioritizing building blocks for combinatorial medicinal chemistry
      represents an optimization task. We present the application of an artificial ant
      colony algorithm to combinatorial molecular design (Molecular Ant Algorithm
      [MAntA]). RESULTS: In a retrospective evaluation, the ant algorithm performed
      favorably compared with other stochastic optimization methods. Application of
      MAntA to peptide design resulted in new octapeptides exhibiting substantial
      binding to mouse MHC-I (H-2K(b)). In a second study, MAntA generated a new
      functional factor Xa inhibitor by Ugi-type three-component reaction. CONCLUSION:
      This proof-of-concept study validates artificial ant systems as innovative
      computational tools for efficient building block prioritization in combinatorial
      chemistry. Focused activity-enriched compound collections are obtained without
      the need for exhaustive product enumeration.

PMID- 24575966
TI  - Predictive in silico off-target profiling in drug discovery.
AB  - Drug action can be rationalized as interaction of a molecule with proteins in a
      regulatory network of targets from a specific biological system. Both drug and
      side effects are often governed by interaction of the drug molecule with many,
      often unrelated, targets. Accordingly, arrays of protein-ligand interaction data
      from numerous in vitro profiling assays today provide growing evidence of
      polypharmacological drug interactions, even for marketed drugs. In vitro off
      target profiling has therefore become an important tool in early drug discovery
      to learn about potential off-target liabilities, which are sometimes beneficial,
      but more often safety relevant. The rapidly developing field of in silico
      profiling approaches is complementing in vitro profiling. These approaches
      capitalize from large amounts of biochemical data from multiple sources to be
      exploited for optimizing undesirable side effects in pharmaceutical research.
      Therefore, current in silico profiling models are nowadays perceived as valuable
      tools in drug discovery, and promise a platform to support optimally informed
      decisions. 

PMID- 24575967
TI  - Exploiting structural information for drug-target assessment.
AB  - The amount of known protein structures is continuously growing, exhibited in over
      95,000 3D structures freely available via the PDB. Over the last decade,
      pharmaceutical research has sparked interest in computationally extracting
      information from this large data pool, resulting in a homology-driven knowledge
      transfer from annotated to new structures. Studying protein structures with
      respect to understanding and modulating their functional behavior means analyzing
      their centers of action. Therefore, the detection and description of potential
      binding sites on the protein surface is a major step towards protein
      classification and assessment. Subsequently, these representations can be
      incorporated to compare proteins, and to predict their druggability or function.
      Especially in the context of target identification and polypharmacology,
      automated tools for large-scale target comparisons are highly needed. In this
      article, developments for automated structure-based target assessment are
      reviewed and remaining challenges as well as future perspectives are discussed. 

PMID- 24575968
TI  - Reverse docking: a powerful tool for drug repositioning and drug rescue.
AB  - Reverse or inverse docking is proving to be a powerful tool for drug
      repositioning and drug rescue. It involves docking a small-molecule drug/ligand
      in the potential binding cavities of a set of clinically relevant macromolecular
      targets. Detailed analyses of the binding characteristics lead to ranking of the
      targets according to the tightness of binding. This process can potentially
      identify novel molecular targets for the drug/ligand which may be relevant for
      its mechanism of action and/or side effect profile. Another potential application
      of reverse docking is during the lead discovery and optimization stages of the
      drug-discovery cycle. This review summarizes the state-of-the-art and future
      prospects of the reverse docking with particular emphasis on computational
      molecular design. 

PMID- 24575969
TI  - Structure-based design of small-molecule protein-protein interaction modulators:
      the story so far.
AB  - As the pivotal role of protein-protein interactions in cell growth,
      transcriptional activity, intracellular trafficking, signal transduction and
      pathological conditions has been assessed, experimental and in silico strategies
      have been developed to design protein-protein interaction modulators. State-of
      the-art structure-based design methods, mainly pharmacophore modeling and
      docking, which have succeeded in the identification of enzyme inhibitors,
      receptor agonists and antagonists, and new tools specifically conceived to target
      protein-protein interfaces (e.g., hot-spot and druggable pocket prediction
      methods) have been applied in the search for small-molecule protein-protein
      interaction modulators. Many successful applications of structure-based design
      approaches that, despite the challenge of targeting protein-protein interfaces
      with small molecules, have led to the identification of micromolar and
      submicromolar hits are reviewed here. 

PMID- 24575970
TI  - Antiepileptic drug use in seven electronic health record databases in Europe: a
      methodologic comparison.
AB  - OBJECTIVE: The annual prevalence of antiepileptic drug (AED) prescribing reported
      in the literature differs considerably among European countries due to use of
      different type of data sources, time periods, population distribution, and
      methodologic differences. This study aimed to measure prevalence of AED
      prescribing across seven European routine health care databases in Spain,
      Denmark, The Netherlands, the United Kingdom, and Germany using a standardized
      methodology and to investigate sources of variation. METHODS: Analyses on the
      annual prevalence of AEDs were stratified by sex, age, and AED. Overall
      prevalences were standardized to the European 2008 reference population. RESULTS:
      Prevalence of any AED varied from 88 per 10,000 persons (The Netherlands) to 144
      per 10,000 in Spain and Denmark in 2001. In all databases, prevalence increased
      linearly: from 6% in Denmark to 15% in Spain each year since 2001. This increase
      could be attributed entirely to an increase in "new," recently marketed AEDs
      while prevalence of AEDs that have been available since the mid-1990s, hardly
      changed. AED use increased with age for both female and male patients up to the
      ages of 80 to 89 years old and tended to be somewhat higher in female than in
      male patients between the ages of 40 and 70. No differences between databases in
      the number of AEDs used simultaneously by a patient were found. SIGNIFICANCE: We
      showed that during the study period of 2001-2009, AED prescribing increased in
      five European Union (EU) countries and that this increase was due entirely to the
      newer AEDs marketed since the 1990s. Using a standardized methodology, we showed
      consistent trends across databases and countries over time. Differences in age
      and sex distribution explained only part of the variation between countries.
      Therefore, remaining variation in AED use must originate from other differences
      in national health care systems.

PMID- 24575971
TI  - The neonatal nurses' view of their role in emotional support of parents and its
      complexities.
AB  - AIMS AND OBJECTIVES: To explore the nurses' views of their role both in the
      neonatal intensive care unit and in the provision of interacting with, and
      emotionally supporting, families. BACKGROUND: The neonatal intensive care nurse
      has a large and complex clinical role and also a role of emotional supporter for
      parents in the neonatal intensive care unit. Identifying components of their role
      and recognising the elements within the nursery that obstruct or encourage this
      role can allow for modification of nurse education and peer support. DESIGN:
      Qualitative study based on semistructured interviews. METHODS: Nine neonatal
      nurses from a single neonatal intensive care unit were interviewed and the data
      analysed thematically using NVIVO version 10. RESULTS: Participants viewed their
      role as an enjoyable yet difficult one, requiring seniority, training and
      experience. They provided support to parents by communicating, listening,
      providing individualised support and by encouraging parental involvement with
      their baby. Constructive elements that contributed to the provision of support
      included a positive neonatal intensive care unit environment and providing a
      parent support group. More obstructive elements were a lack of physical neonatal
      intensive care unit space, little time available for nurse-to-parent conversation
      and language and cultural barriers between nurses and parents. CONCLUSION: The
      role of the neonatal nurse in providing emotional support is complex and requires
      a high level of ongoing support and education for staff, and minimisation of
      physical and staff-related obstructions. RELEVANCE TO CLINICAL PRACTICE: The
      modern neonatal intensive care unit offers complex medical and nursing services
      and with this care comes higher needs from both babies and their parents.
      Neonatal intensive care unit nurses should be supported in their roles by having
      peer support available in the neonatal intensive care unit and education and
      training in emotional support and counselling skills. The nursing staff also
      require a comfortable and practical physical working space in which to assist
      parents to be with their baby.

PMID- 24575973
TI  - Recent studies of genetic dysfunction in pelvic organ prolapse: the role of
      collagen defects.
AB  - Gynaecologists are becoming increasingly aware that women with a family history
      of prolapse are at an increased risk of prolapse refractory to treatment. In the
      past five years, several genetic mutations have been shown to correlate with
      increased prolapse susceptibility. These mutations can result in disordered
      collagen metabolism, which weaken the fascial support of the pelvic organs. This
      review examines the contemporary evidence regarding the role of collagen in
      prolapse. 

PMID- 24575972
TI  - Religiosity and sexual risk behaviors among African American cocaine users in the
      rural South.
AB  - PURPOSE: Racial and geographic disparities in human immunodeficency virus (HIV)
      are dramatic and drug use is a significant contributor to HIV risk. Within the
      rural South, African Americans who use drugs are at extremely high risk. Due to
      the importance of religion within African American and rural Southern
      communities, it can be a key element of culturally-targeted health promotion with
      these populations. Studies have examined religion's relationship with sexual risk
      in adolescent populations, but few have examined specific religious behaviors and
      sexual risk behaviors among drug-using African American adults. This study
      examined the relationship between well-defined dimensions of religion and
      specific sexual behaviors among African Americans who use cocaine living in the
      rural southern United States. METHODS: Baseline data from a sexual risk reduction
      intervention for African Americans who use cocaine living in rural Arkansas (N =
      205) were used to conduct bivariate and multivariate analyses examining the
      association between multiple sexual risk behaviors and key dimensions of religion
      including religious preference, private and public religious participation,
      religious coping, and God-based, congregation-based, and church leader-based
      religious support. FINDINGS: After adjusting individualized network estimator
      weights based on the recruitment strategy, different dimensions of religion had
      inverse relationships with sexual risk behavior, including church leadership
      support with number of unprotected vaginal/anal sexual encounter and positive
      religious coping with number of sexual partners and with total number of
      vaginal/anal sexual encounters. CONCLUSION: Results suggest that specific
      dimensions of religion may have protective effects on certain types of sexual
      behavior, which may have important research implications.

PMID- 24575975
TI  - Tetraphenylethylene-based expanded oxacalixarene: synthesis, structure, and its
      supramolecular grid assemblies directed by guests in the solid state.
AB  - A novel TPE-based expanded oxacalixarene with typical aggregation-induced
      emission properties was synthesized by the SNAr reaction of
      dihydroxytetraphenylethylene with 2,6-dichloropyrazine. The conformation of the
      oxacalixarene is adjusted by the encapsulated guests (benzene or THF), which
      results in different supramolecular grid structures in the solid state. 

PMID- 24575974
TI  - Amyloid beta peptide conformational changes in the presence of a lipid membrane
      system.
AB  - Here we are presenting a comparative analysis of conformational changes of two
      amyloid beta peptides, Abeta(25-35) and Abeta(1-42), in the presence and absence
      of a phospholipid system, namely, POPC/POPS (1-palmitoyl-2
      oleoylphospatidylcholine/palmitoyl-2-oleoylphospatidylserine), through Raman
      spectroscopy, synchrotron radiation micro Fourier-transform infrared
      spectroscopy, and micro X-ray diffraction. Ringlike samples were obtained from
      the evaporation of pure and mixed solutions of the proteins together with the
      POPC/POPS system on highly hydrophilic substrates. The results confirm the
      presence of a alpha-helical to beta-sheet transition from the internal rim of the
      ringlike samples to the external one in the pure Abeta(25-35) residual, probably
      due to the convective flow inside the droplets sitting on highly hydrophilic
      substrates enhancing the local concentration of the peptide at the external edge
      of the dried drop. In contrast, the presence of POPC/POPS lipids in the peptide
      does not result in alpha-helical structures and introduces the presence of
      antiparallel beta-sheet material together with parallel beta-sheet structures and
      possible beta-turns. As a control, Abeta(1-42) peptide was also tested and shows
      beta-sheet conformations independently from the presence of the lipid system. The
      MUXRD analysis further confirmed these conclusions, showing how the absence of
      the phospholipid system induces in the Abeta(25-35) a probable composite
      alpha/beta material while its coexistence with the peptide leads to a not
      oriented beta-sheet conformation. These results open interesting scenarios on the
      study of conformational changes of Abeta peptides and could help, with further
      investigations, to better clarify the role of enzymes and alternative lipid
      systems involved in the amyloidosis process of Abeta fragments. 

PMID- 24575976
TI  - Gemcitabine resistance is associated with epithelial-mesenchymal transition and
      induction of HIF-1alpha in pancreatic cancer cells.
AB  - Pancreatic cancer is one of the highly aggressive malignant diseases worldwide.
      To achieve better treatment outcome of pancreatic cancer, in the current study we
      explore the underlying molecular mechanism of drug resistance in pancreatic
      cancer cells. We found that resistance to gemcitabine is associated with
      epithelial-mesenchymal transition (EMT) phenotype in a panel of pancreatic cancer
      cell lines. Notably, gemcitabine-resistant pancreatic cancer cells acquire EMT
      phenotype. Moreover, gemcitabine-resistant cells have increased migration and
      invasion activities. Furthermore, we observed the high expression of HIF-1alpha
      in gemcitabine-resistant cells. More importantly, inhibition of HIF-1alpha in
      gemcitabine-resistant cells caused partial reversal of EMT phenotype, suggesting
      that HIF-1alpha was critically involved in gemcitabine-resistant-mediated EMT.
      Therefore, targeting HIF-1alpha could be an effective strategy for the treatment
      of pancreatic cancer. 

PMID- 24575977
TI  - Comparative mutant prevention concentration and antibacterial activity of
      fluoroquinolones against Escherichia coli in diarrheic buffalo calves.
AB  - Owing to emerging threat of antimicrobial resistance, mutant prevention
      concentration (MPC) is considered as an important parameter to evaluate the
      antimicrobials for their capacity to restrict/allow the emergence of resistant
      mutants. Therefore, MPCs of ciprofloxacin, enrofloxacin, levofloxacin,
      moxifloxacin, and norfloxacin were determined against Escherichia coli isolates
      of diarrheic buffalo calves. The minimum inhibitory concentrations (MICs) and
      minimum bactericidal concentrations (MBCs) were also established. The MICs of
      ciprofloxacin, enrofloxacin, levofloxacin, moxifloxacin and norfloxacin were
      0.009, 0.022, 0.024, 0.028, and 0.036 MUg/ml, respectively. The MBCs obtained
      were very close to the MICs of respective drugs that suggested a bactericidal
      mode of action of antimicrobials. The MPCs (MUg/ml) of ciprofloxacin (4.2*MIC),
      moxifloxacin (4.8*MIC), and norfloxacin (5.1*MIC) were approximately equal but
      slightly lower than enrofloxacin (7.6*MIC) and levofloxacin (8.5*MIC) against
      clinical isolates of E. coli. The MPC data suggested that enrofloxacin has the
      potential for restricting the selection of E. coli mutants during treatment at
      appropriate dosing. 

PMID- 24575978
TI  - Exploration of Zn resonance levels and thermoelectric properties in I-doped PbTe
      with ZnTe nanostructures.
AB  - Motivated by the theoretically predicted Zn resonant states in the conduction
      band of PbTe, in the present work, we investigated the effect of Zn substitution
      on the thermoelectric properties in I-doped n-type PbTe. The room temperature
      thermopower values show good agreement with the theoretical Pisarenko plot of
      PbTe up to a carrier concentration of 4.17 * 10(19) cm(-3); thus, the presence of
      Zn resonance levels is not observed. Because of the low solubility of Zn in PbTe,
      a second phase of coherent ZnTe nanostructures is observed within the PbTe host
      matrix, which is found to reduce the lattice thermal conductivity. The reduced
      lattice thermal conductivity in PbTe by ZnTe nanostructures leads to notable
      enhancement in the figure of merit with a maximum value of 1.35 at 650 K. In
      contrast to the recent literature, the carrier mobility is not found to be
      affected by the band offset between ZnTe nanostructures and PbTe. This is
      explained by the quantum tunneling of the charge carrier through the narrow
      offset barrier and depletion width and coherent nature of the interface boundary
      between the two phases, i.e., ZnTe and PbTe. 

PMID- 24575979
TI  - Lactobacillus bulgaricus mutants decompose uremic toxins.
AB  - BACKGROUND/AIMS: We aim to obtain a probiotic strain from Lactobacillus
      bulgaricus by testing its capability to decompose uremic toxins to provide new
      intestinal bacteria for the treatment of chronic renal failure. METHODS: Original
      L. bulgaricus was cultured with the serum of uremic patients and then mutated by
      physical (ultraviolet) and chemical (diethyl sulfate) methods repeatedly. Using
      creatinine decomposition rate as an observed index, we selected the best strains
      which decreased the most concentration of the creatinine. We then tested its
      ability to decompose urea, uric acid, serum phosphate, parathyroid hormone, and
      homocysteine and its genetic stability. RESULTS: After inductive and mutagenic
      treatment, DUC3-17 was selected. Its decomposition rate of creatinine, urea
      nitrogen, uric acid, phosphorus, parathyroid hormone, and homocysteine were
      17.23%, 36.02%, 9.84%, 15.73%, 78.26%, and 12.69%, respectively. The degrading
      capacity was sustained over five generations. CONCLUSIONS: After directional
      induction and compound mutation, L. bulgaricus has greater capacity to decompose
      uremic toxins, with a stable inheritance.

PMID- 24575980
TI  - Human chorionic gonadotropin, angiogenic factors, and preeclampsia risk: a nested
      case-control study.
AB  - OBJECTIVE: To study whether human chorionic gonadotropin concentrations during
      pregnancy or combinations of human chorionic gonadotropin and other angiogenic
      factors, soluble fms-like tyrosine kinase 1 and placental growth factor (PlGF),
      are associated with preeclampsia risk. DESIGN: Nested case-control study.
      SETTING: Population cohort of pregnant women. SAMPLE: A total of 121 cases of
      preterm (<37 weeks) and 158 cases of term preeclampsia (>=37 weeks of gestation)
      and 356 women without preeclampsia (controls). METHODS: Women with preeclampsia
      were identified by linkage to the Medical Birth Registry of Norway.
      Concentrations of human chorionic gonadotropin, soluble fms-like tyrosine kinase
      1 and PlGF were measured in maternal serum samples collected in each trimester of
      pregnancy. MAIN OUTCOME MEASURES: Odds ratios of preterm and term preeclampsia.
      RESULTS: High human chorionic gonadotropin concentrations (highest quartile) in
      the first trimester were associated with reduced risk for preterm preeclampsia
      (OR 0.3, 95% CI 0.1-0.9), compared with low human chorionic gonadotropin (lowest
      quartile), whereas high human chorionic gonadotropin concentrations in the second
      trimester were associated with increased risk for preterm preeclampsia (OR 4.0,
      95% CI 1.8-8.9). High human chorionic gonadotropin concentrations in the third
      trimester were associated with increased risk for term preeclampsia (OR 4.8, 95%
      CI 1.8-13.3). Concentrations of human chorionic gonadotropin above the median
      value combined with PlGF below the median in the second trimester were associated
      with very high risk for preterm preeclampsia (OR 36.9, 95% CI 8.2-165.8).
      CONCLUSIONS: The results suggest an important role of human chorionic
      gonadotropin in the pathophysiological processes that lead to preeclampsia. The
      combined association of human chorionic gonadotropin and PlGF indicates a
      possible synergism between underlying biological pathways.

PMID- 24575982
TI  - Risk prediction score for death of traumatised and injured children.
AB  - BACKGROUND: Injury prediction scores facilitate the development of clinical
      management protocols to decrease mortality. However, most of the previously
      developed scores are limited in scope and are non-specific for use in children.
      We aimed to develop and validate a risk prediction model of death for injured and
      Traumatised Thai children. METHODS: Our cross-sectional study included 43,516
      injured children from 34 emergency services. A risk prediction model was derived
      using a logistic regression analysis that included 15 predictors. Model
      performance was assessed using the concordance statistic (C-statistic) and the
      observed per expected (O/E) ratio. Internal validation of the model was performed
      using a 200-repetition bootstrap analysis. RESULTS: Death occurred in 1.7% of the
      injured children (95% confidence interval [95% CI]: 1.57-1.82). Ten predictors
      (i.e., age, airway intervention, physical injury mechanism, three injured body
      regions, the Glasgow Coma Scale, and three vital signs) were significantly
      associated with death. The C-statistic and the O/E ratio were 0.938 (95% CI:
      0.929-0.947) and 0.86 (95% CI: 0.70-1.02), respectively. The scoring scheme
      classified three risk stratifications with respective likelihood ratios of 1.26
      (95% CI: 1.25-1.27), 2.45 (95% CI: 2.42-2.52), and 4.72 (95% CI: 4.57-4.88) for
      low, intermediate, and high risks of death. Internal validation showed good model
      performance (C-statistic = 0.938, 95% CI: 0.926-0.952) and a small calibration
      bias of 0.002 (95% CI: 0.0005-0.003). CONCLUSIONS: We developed a simplified Thai
      pediatric injury death prediction score with satisfactory calibrated and
      discriminative performance in emergency room settings.

PMID- 24575983
TI  - The Surgeon Generals' reports and respiratory diseases. From 1964 to 2014.

PMID- 24575986
TI  - The emergence of e-cigarettes: a triumph of wishful thinking over science.

PMID- 24575984
TI  - Objective factors associated with physicians' and nurses' perceptions of
      intensive care unit capacity strain.
AB  - RATIONALE: Time-varying demand for critical care may strain the capacities of
      intensive care units (ICUs) to provide optimal care. Intensivists and ICU nurses
      may be the best judges of the strain on their ICU. Yet, it is not clear what ICU
      and hospital factors contribute to this perceived sense of strain among ICU
      providers. OBJECTIVES: To identify measureable ICU and hospital factors
      associated with perceived strain by intensivists and ICU nurses. METHODS: During
      a 6-month prospective cohort study, we surveyed nurses and physicians responsible
      for bed management regarding the ability of a 24-bed medical ICU (MICU) to
      provide optimal critical care. We simultaneously assessed time-varying ICU-level
      factors, including patient census, number of admissions, average patient acuity,
      number of interhospital transfer requests, and censuses of other hospital units.
      To identify factors associated with strain, we used an algorithm for covariate
      selection in regression models that selects variables that contribute
      sufficiently to model prediction to justify their inclusion. MEASUREMENTS AND
      MAIN RESULTS: Of 254 surveys, 226 (89%) were completed by 18 charge nurses and 17
      physicians. On a scale of 1 to 10 (where a higher score indicated more strain),
      the median perceived strain score among nurses was 6 (interquartile range, 3-7)
      and among physicians was 5 (interquartile range, 3-7), with moderate correlation
      within days (interclass correlation coefficient, 0.45; 95% confidence interval:
      0.30, 0.60). Average patient acuity, MICU census, number of MICU admissions, and
      general ward census were included in the most efficient model of strain perceived
      by nurses. Only MICU census was strongly associated with strain perceived by
      physicians. CONCLUSIONS: A model containing commonly available metrics of ICU
      census, average patient acuity, and the proportion of new admissions has validity
      as a model of ICU nurses' perceived ICU capacity strain. However, only ICU census
      was associated with increased perceived capacity strain by physicians,
      highlighting the need for involvement of multiple stakeholder groups to improve
      our understanding of ICU capacity strain.

PMID- 24575987
TI  - What we talk about when we talk about intensive care unit strain.

PMID- 24575988
TI  - Is vitamin D deficiency the root of all pulmonary evils?

PMID- 24575989
TI  - Editors' introduction to ATS Reports: Medical education.

PMID- 24575990
TI  - How far we have come in the last 50 years in smoking attitudes and actions.
AB  - Dramatic changes in smoking behavior and attitudes about smoking have occurred
      over the 50-year interval since the release of the 1964 smoking and health report
      to the Surgeon General. Between 1965 and 2011, adult prevalence of cigarette
      smoking fell from 51.9 to 21.6% among men and from 33.9 to 16.5% among women,
      with an increasing fraction of smokers who do not smoke every day. Federal taxes
      have increased from $0.08 in 1965 to $1.01, with even larger increases in many
      state taxes. Workplace restrictions on smoking have increased from only 3% of
      workers protected by workplace smoking bans in 1986 (e.g., those working in
      fireworks factories) to more than 70% of workers being protected in 1999. Equally
      dramatic changes have occurred in restrictions on smoking in the home. The
      evaporation of the remaining societal support for smoking may be an important
      part of the "end game" for cigarette smoking in the United States. 

PMID- 24575991
TI  - Tobacco control policies and their impacts. Past, present, and future.
AB  - The 1964 Surgeon General's report on smoking and health concluded that "Cigarette
      smoking is a health hazard of sufficient importance in the United States to
      warrant appropriate remedial action." The adoption of remedial actions over the
      next half century produced what is arguably the most important public health
      triumph of that period in the United States and in other developed nations. At
      the heart of the remedial actions were governmental policies. By raising
      cigarette price, taxation is especially effective at reducing smoking,
      encouraging some smokers to quit and others to reduce their daily consumption,
      while also discouraging the initiation of smoking by children. Smoke-free
      workplace policies have dramatically reduced workers' exposure to the toxins in
      cigarette smoke, smoking, employers' costs, and the incidence of acute myocardial
      infarctions. Other policies have also helped diminish the toll of smoking. The
      successes of tobacco control notwithstanding, future progress will occur slowly
      unless society finds new, possibly radical "endgame" strategies to hasten the
      arrival of a smoke-free society. 

PMID- 24575992
TI  - Emerging nicotine delivery products. Implications for public health.
AB  - The idea of clean nicotine delivery systems that would satisfy nicotine craving
      and promote smoking cessation has been considered as a possible public health
      tool for many years. Nicotine medications have been useful for smoking cessation
      but have not found widespread popularity among smokers, perhaps because of slow
      nicotine delivery and other sensory characteristics that differ from cigarettes.
      Traditional smokeless tobacco delivers as much nicotine as cigarettes and has
      been advocated for harm reduction but contains carcinogenic nitrosamines and has
      not been proven to promote cessation. Furthermore, there is concern that dual use
      of smokeless tobacco and cigarettes may inhibit quitting smoking. Newer oral
      dissolvable tobacco products contain lower levels of toxicants than other
      smokeless tobacco but also deliver much less nicotine and have not been popular
      with consumers. Electronic cigarettes that aerosolize nicotine without generating
      toxic tobacco combustion products have become quite popular and hold promise as a
      way to attract smokers away from cigarettes, although efficacy in promoting
      smoking cessation has not yet been demonstrated. There are concerns about safety
      of long-term use, and there is evidence that youth, including nonsmokers, are
      taking up e-cigarette use. E-cigarettes are marketed for use when one cannot
      smoke conventional cigarettes, and such use might result in more persistent
      cigarette smoking. Although their benefits and risks are being vigorously
      debated, e-cigarettes or other clean nicotine delivery devices could play an
      important role as an adjunct to a U.S. Food and Drug Administration regulatory
      intervention to make cigarettes less addictive and in this context could
      contribute to the end of cigarette smoking and smoking-induced disease. 

PMID- 24575994
TI  - Update on the diagnosis of pulmonary coccidioidomycosis.
AB  - Coccidioidomycosis is a common cause of community-acquired pneumonia in the
      southwest United States, Mexico, and South America. The disease has seen a marked
      increase in incidence in the western United States in the last decade and can be
      acquired by individuals who travel even briefly through an endemic area,
      presenting a diagnostic dilemma for clinicians who are not familiar with the
      disease. The clinical and radiographic manifestations of pulmonary
      coccidioidomycosis often mimic those of other causes of pneumonia. However,
      because treatment recommendations and the potential for chronic sequelae of acute
      infection differ substantially from those for bacterial community-acquired
      pneumonia, accurate, timely diagnosis of coccidioidomycosis is paramount. A
      number of diagnostic tests are available with varying sensitivity and
      specificity, making the approach complex. Radiographic features, although
      nonspecific, sometimes demonstrate patterns more suggestive of coccidioidomycosis
      than bacterial community-acquired pneumonias. A routine blood count may reveal
      eosinophilia. Serologic testing is used most widely but may be negative early in
      the course of disease, potentially leading to misdiagnosis with subsequent
      inappropriate treatment and follow-up. The sensitivity of serologic testing is
      lower in immunocompromised patients, a population at the highest risk for
      developing severe disease. When clinically appropriate, other biologic specimens,
      such as sputum, bronchoalveolar lavage fluid, or lung biopsies, may allow for
      rapid, definitive diagnosis. In light of the significantly increased incidence
      and complexities in diagnosis of coccidioidomycosis, we examine the diagnostic
      approach and provide examples of classic clinical and radiographic presentations,
      discuss the utility of serologic testing, and suggest algorithms that may aid in
      the diagnosis. 

PMID- 24575993
TI  - Electronic cigarettes. Potential harms and benefits.
AB  - Use of electronic cigarettes, devices that deliver a nicotine-containing vapor,
      has increased rapidly across the country and globally. Perceived and marketed as
      a "healthier alternative" to conventional cigarettes, few data exist regarding
      the safety of these devices and their efficacy in harm reduction and treatment of
      tobacco dependence; even less is known about their overall impact on population
      health. This review highlights the recent data regarding electronic cigarette
      toxicity, impact on lung function, and efficacy in smoking reduction and
      cessation. Studies show that the vapor generated from electronic cigarettes has
      variable amounts of nicotine and potential harmful toxins, albeit at levels lower
      than in conventional cigarettes. The long-term carcinogenic and lung function
      effects of electronic cigarettes are not known. Although some data demonstrate
      that electronic cigarettes may be effective in reducing conventional cigarette
      consumption, there are no data demonstrating the efficacy of electronic
      cigarettes as a tool to achieve cessation. Until robust longitudinal evaluations
      demonstrate the safety of electronic cigarettes and efficacy in treatment of
      tobacco dependence, their role as a harm reduction tool is unclear. 

PMID- 24575995
TI  - Career development for the clinician-educator. Optimizing impact and maximizing
      success.
AB  - Health care professionals in pulmonary, critical care, and sleep medicine play
      key roles as teachers for learners of all levels in both clinical care and
      scientific investigation. Teaching excellence requires training in principles of
      adult learning and the acquisition and practice of key professional skills
      including assessment and feedback techniques, curriculum development, and
      strategies for effective teaching across venues ranging from the bedside to the
      lecture hall. Those interested in pursuing teaching as the focus of their
      academic career and basis for promotion should invest in professional development
      as a teacher and educator. Professional development activities include obtaining
      additional training as a teacher in dedicated medical education fellowships or
      serving as a peer observer or being observed by a fellow teacher. Numerous
      additional options for training as a teacher and educator are now available
      including resource repositories, continuing medical education courses, and online
      training modules. Those with an interest in medical education research may
      benefit from enrollment in masters or other advanced degree programs focused on
      the qualitative and quantitative methods and other key research skills. Aspiring
      clinician-educators should also seek out opportunities to participate in a
      community of medical educators locally, regionally, nationally, and
      internationally. At each of these levels, there exist opportunities to contribute
      to course or program design, development, and evaluation. Finally, for those
      interested in promotion as an academic clinician-educator, there are increasing
      requirements to produce academic scholarship ranging from curricular materials to
      journal articles focused on education and education research. 

PMID- 24575996
TI  - Engaging patients in public policy advocacy.
AB  - Health professionals can and should be game-changing influencers of U.S. health
      policies. The American Thoracic Society (ATS) is enabling its members to advocate
      on important issues through such initiatives as the Breathing Better Alliance
      network and the annual ATS Hill Day. Patients are also organizing to make their
      voices heard by participating in the member organizations of the ATS Public
      Advisory Roundtable and by accompanying ATS members and staff on visits to
      legislators and government regulators. If we join together, we can amplify our
      messages and promote better health policies. Doing so will require us to embrace
      a partnership steeped in trust and hope. 

PMID- 24575997
TI  - Management strategies to effect change in intensive care units: lessons from the
      world of business. Part I. Targeting quality improvement initiatives.
AB  - The business community has developed strategies to ensure the quality of the
      goods or services they produce and to improve the management of multidisciplinary
      work teams. With modification, many of these techniques can be imported into
      intensive care units (ICUs) to improve clinical operations and patient safety. In
      Part I of a three-part ATS Seminar series, we argue for adopting business
      management strategies in ICUs and set forth strategies for targeting selected
      quality improvement initiatives. These tools are relevant to health care today as
      focus is placed on limiting low-value care and measuring, reporting, and
      improving quality. In the ICU, the complexity of illness and the need to
      standardize processes make these tools even more appealing. Herein, we highlight
      four techniques to help prioritize initiatives. First, the "80/20 rule" mandates
      focus on the few (20%) interventions likely to drive the majority (80%) of
      improvement. Second, benchmarking--a process of comparison with peer units or
      institutions--is essential to identifying areas of strength and weakness. Third,
      root cause analyses, in which structured retrospective reviews of negative events
      are performed, can be used to identify and fix systems errors. Finally, failure
      mode and effects analysis--a process aimed at prospectively identifying potential
      sources of error--allows for systems fixes to be instituted in advance to prevent
      negative outcomes. These techniques originated in fields other than health care,
      yet adoption has and can help ICU managers prioritize issues for quality
      improvement.

PMID- 24575998
TI  - A case of unilateral hyperlucent lung.

PMID- 24575999
TI  - Reply: Episodic breathlessness: a clinically relevant and rising issue.

PMID- 24576000
TI  - Episodic breathlessness: a clinically relevant and rising issue.

PMID- 24576001
TI  - Chronic obstructive pulmonary disease fact sheets from the Centers for Disease
      Control and Prevention.

PMID- 24576002
TI  - Crystal structure and interaction of phycocyanin with beta-secretase: A putative
      therapy for Alzheimer's disease.
AB  - Alzheimer's disease (AD) represents a neurological disorder, which is caused by
      enzymatic degradation of an amyloid precursor protein into short peptide
      fragments that undergo association to form insoluble plaques. Preliminary studies
      suggest that cyanobacterial extracts, especially the light-harvesting protein
      phycocyanin, may provide a means to control the progression of the disease.
      However, the molecular mechanism of disease control remains elusive. In the
      present study, intact hexameric phycocyanin was isolated and crystallized from
      the cyanobacterium Leptolyngbya sp. N62DM, and the structure was solved to a
      resolution of 2.6 A. Molecular docking studies show that the phycocyanin
      alphabeta-dimer interacts with the enzyme beta-secretase, which catalyzes the
      proteolysis of the amyloid precursor protein to form plaques. The molecular
      docking studies suggest that the interaction between phycocyanin and beta
      secretase is energetically more favorable than previously reported inhibitor-beta
      secretase interactions. Transgenic Caenorhabditis elegans worms, with a genotype
      to serve as an AD-model, were significantly protected by phycocyanin. Therefore,
      the present study provides a novel structure-based molecular mechanism of
      phycocyanin-mediated therapy against AD.

PMID- 24576004
TI  - Assessment of a generalizable methodology to assess learning from manikin-based
      simulation technology.
AB  - Objective : This study combined a learning outcomes-based checklist and salient
      characteristics derived from wisdom-of-crowds theory to test whether differing
      groups of judges (diversity maximized versus expertise maximized) would be able
      to appropriately assess videotaped, manikin-based simulation scenarios. Methods :
      Two groups of 3 judges scored 9 videos of interns managing a simulated cardiac
      event. The first group had a diverse range of knowledge of simulation procedures,
      while the second group was more homogeneous in their knowledge and had greater
      simulation expertise. All judges viewed 3 types of videos (predebriefing,
      postdebriefing, and 6 month follow-up) in a blinded fashion and provided their
      scores independently. Intraclass correlation coefficients (ICCs) were used to
      assess the reliability of judges as related to group membership. Scores from each
      group of judges were averaged to determine the impact of group on scores. Results
      : Results revealed strong ICCs for both groups of judges (diverse, 0.89; expert,
      0.97), with the diverse group of judges having a much wider 95% confidence
      interval for the ICC. Analysis of variance of the average checklist scores
      indicated no significant difference between the 2 groups of judges for any of the
      types of videotapes assessed (F = 0.72, p = .4094). There was, however, a
      statistically significant difference between the types of videos (F = 14.39, p =
      .0004), with higher scores at the postdebrief and 6-month follow-up time periods.
      Conclusions : Results obtained in this study provide optimism for assessment
      procedures in simulation using learning outcomes-based checklists and a small
      panel of judges. 

PMID- 24576005
TI  - Life cycle inventory of the production of rare earths and the subsequent
      production of NdFeB rare earth permanent magnets.
AB  - Neodymium is one of the more critical rare earth elements with respect to current
      availability and is most often used in high performance magnets. In this paper,
      we compare the virgin production route of these magnets with two hypothetical
      recycling processes in terms of environmental impact. The first recycling process
      looks at manual dismantling of computer hard disk drives (HDDs) combined with a
      novel hydrogen based recycling process. The second process assumes HDDs are
      shredded. Our life cycle assessment is based both on up to date literature and on
      our own experimental data. Because the production process of neodymium oxide is
      generic to all rare earths, we also report the life cycle inventory data for the
      production of rare earth oxides separately. We conclude that recycling of
      neodymium, especially via manual dismantling, is preferable to primary
      production, with some environmental indicators showing an order of magnitude
      improvement. The choice of recycling technology is also important with respect to
      resource recovery. While manual disassembly allows in principle for all magnetic
      material to be recovered, shredding leads to very low recovery rates (<10%). 

PMID- 24576006
TI  - The contribution of spontaneous mutations to thermal sensitivity curve variation
      in Drosophila serrata.
AB  - Many traits studied in ecology and evolutionary biology change their expression
      in response to a continuously varying environmental factor. One well-studied
      example are thermal performance curves (TPCs); continuous reaction norms that
      describe the relationship between organismal performance and temperature and are
      useful for understanding the trade-offs involved in thermal adaptation. We
      characterized curves describing the thermal sensitivity of voluntary locomotor
      activity in a set of 66 spontaneous mutation accumulation lines in the fly
      Drosophila serrata. Factor-analytic modeling of the mutational variance
      covariance matrix, M, revealed support for three axes of mutational variation in
      males and two in females. These independent axes of mutational variance
      corresponded well to the major axes of TPC variation required for different types
      of thermal adaptation; "faster-slower" representing changes in performance
      largely independent of temperature, and the "hotter-colder" and "generalist
      specialist" axes, representing trade-offs. In contrast to its near-absence from
      standing variance in this species, a "faster-slower" axis, accounted for most
      mutational variance (75% in males and 66% in females) suggesting selection may
      easily fix or remove these types of mutations in outbred populations. Axes
      resembling the "hotter-colder" and "generalist-specialist" modes of variation
      contributed less mutational variance but nonetheless point to an appreciable
      input of new mutations that may contribute to thermal adaptation. 

PMID- 24576007
TI  - Photosystem I protein films at electrode surfaces for solar energy conversion.
AB  - Over the course of a few billion years, nature has developed extraordinary
      nanomaterials for the efficient conversion of solar energy into chemical energy.
      One of these materials, photosystem I (PSI), functions as a photodiode capable of
      generating a charge separation with nearly perfect quantum efficiency. Because of
      the favorable properties and natural abundance of PSI, researchers around the
      world have begun to study how this protein complex can be integrated into modern
      solar energy conversion devices. This feature article describes some of the
      recent materials and methods that have led to dramatic improvements (over several
      orders of magnitude) in the photocurrents and photovoltages of biohybrid
      electrodes based on PSI, with an emphasis on the research activities in our
      laboratory. 

PMID- 24576009
TI  - High-volume lesions using a new second-generation open irrigation radiofrequency
      catheter are associated with the development of inhomogeneous lesions.
AB  - BACKGROUND: After catheter ablation there is often a discrepancy between acute
      and chronic success rates. We aimed to evaluate major determinants for lesion
      quality and understand different manifestations of lesion structures. METHODS: In
      a canine thigh muscle model radiofrequency (RF) current was delivered for 60
      seconds at 30 W (n = 39) or 50 W (n = 18) with 15-g contact force. A second
      generation 12-hole gold open irrigation catheter (SGIT) and a first-generation
      six-hole platinum-iridium catheter (FGIT; Biotronik, Berlin, Germany) were used.
      Electrode and tissue temperatures (at the surface and 3.5-mm and 7-mm depth) were
      recorded and lesion dimensions were measured. Lesions with steam pops were
      excluded. Histological examination was performed to evaluate homogeneity of the
      lesions. Inhomogeneity was defined as a visual multiband lesion pattern
      indicating different histological characteristics. RESULTS: In total 57 lesions
      were created. Seventeen lesions were excluded (steam pops) and 40 lesions were
      analyzed. A total number of 11 homogeneous and 29 inhomogeneous lesions were
      identified. Using the SGIT catheter 16.7% of the lesions was homogeneous and
      83.3% inhomogeneous; for FGIT it was 43.8% and 56.2% (P = 0.065), respectively.
      Homogeneous lesions had lower volumes as compared to inhomogeneous lesions (514.0
      +/- 198.8 vs 914.8 +/- 399.1 mm, P = 0.003). Multiple logistic regression
      analysis indicated that the SGIT catheter is a significant predictor for
      inhomogeneous lesions (odds ratio 6.5, 95% confidence interval 1.1-38.8; P =
      0.040) independent from power setting and flow rate. CONCLUSIONS: The development
      of inhomogeneous lesions after acute RF ablation is associated with higher lesion
      volumes and the use of the second-generation irrigation gold-tip catheter.

PMID- 24576008
TI  - The emergence of a global right to health norm--the unresolved case of universal
      access to quality emergency obstetric care.
AB  - BACKGROUND: The global response to HIV suggests the potential of an emergent
      global right to health norm, embracing shared global responsibility for health,
      to assist policy communities in framing the obligations of the domestic state and
      the international community. Our research explores the extent to which this
      global right to health norm has influenced the global policy process around
      maternal health rights, with a focus on universal access to emergency obstetric
      care. METHODS: In examining the extent to which arguments stemming from a global
      right to health norm have been successful in advancing international policy on
      universal access to emergency obstetric care, we looked at the period from 1985
      to 2013 period. We adopted a qualitative case study approach applying a process
      tracing methodology using multiple data sources, including an extensive
      literature review and limited key informant interviews to analyse the
      international policy agenda setting process surrounding maternal health rights,
      focusing on emergency obstetric care. We applied John Kingdon's public policy
      agenda setting streams model to analyse our data. RESULTS: Kingdon's model
      suggests that to succeed as a mobilising norm, the right to health could work if
      it can help bring the problem, policy and political streams together, as it did
      with access to AIDS treatment. Our analysis suggests that despite a normative
      grounding in the right to health, prioritisation of the specific maternal health
      entitlements remains fragmented. CONCLUSIONS: Despite United Nations recognition
      of maternal mortality as a human rights issue, the relevant policy communities
      have not yet managed to shift the policy agenda to prioritise the global right to
      health norm of shared responsibility for realising access to emergency obstetric
      care. The experience of HIV advocates in pushing for global solutions based on
      right to health principles, including participation, solidarity and
      accountability; suggest potential avenues for utilising right to health based
      arguments to push for policy priority for universal access to emergency obstetric
      care in the post-2015 global agenda.

PMID- 24576010
TI  - Evaluating the effects of preoperative fasting and fluid limitation.
AB  - The aim of the study was to evaluate the effects of preoperative fasting and
      fluid limitation in patients undergoing laparoscopic cholecystectomy. Although
      traditional long-term fasting is not recommended in current preoperative
      guidelines, this is still a common intervention. Visual analogue scale was used
      to assess hunger, thirst, sleepiness, exhaustion, nausea and pain; State and
      Trait Anxiety Inventory was used to assess the preoperative anxiety of 99
      patients undergoing elective laparoscopic cholecystectomy. Mean time of
      preoperative fasting and fluid limitation were, respectively, 14.70 +/- 3.14 and
      11.25 +/- 3.74 h. Preoperatively, 58.60% of the patients experienced moderate
      anxiety. Patients fasting 12 h or longer had higher hunger, thirst, nausea and
      pain scores. The mean trait anxiety score of patients fasting 12 h or longer was
      statistically significantly higher. Receiving nothing by mouth after midnight
      preoperatively is a persisted intervention and results in discomfort of patients.
      Clinical protocols should be revised and nurses should be trained in current
      fasting protocols. 

PMID- 24576011
TI  - Predictive factors for the sensitivity of radiotherapy and prognosis of
      esophageal squamous cell carcinoma.
AB  - PURPOSE: To identify predictive biomarkers for radiosensitization and prognosis
      of esophageal squamous cell carcinoma (ESCC). MATERIALS AND METHODS: A total of
      150 advanced stage ESCC patients were treated with preoperative radiotherapy. The
      protein levels of Dicer 1, DNA methyltransferase 1 (Dnmt1), and DNA-dependent
      protein kinase catalytic subunit (DNA-PKcs) and the mRNA levels of Dicer 1,
      Dnmt1, and let-7b microRNA (miRNA) were measured in ESCC tumor tissues before and
      after radiotherapy. Global DNA methylation was measured and terminal
      deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining was
      performed. RESULTS: Negative Dicer 1, Dnmt1, and DNA-PKcs protein expression were
      observed in 72%, 67.3%, and 50.7% of ESCC patients, respectively. Primary Dicer 1
      and Dnmt1 expression positively correlated with radiation sensitization and
      longer survival of ESCC patients, while increased Dicer 1 and Dnmt1 expression
      after radiation correlated with increased apoptosis in residual tumor tissues.
      Dicer 1 and Dnmt1 expression correlated with let-7b miRNA expression and global
      DNA methylation levels, respectively. In contrast, positive DNA-PKcs expression
      negatively correlated with radiation-induced pathological reactions, and
      increased DNA-PKcs expression correlated with increased apoptosis after
      radiation. CONCLUSION: Global DNA hypomethylation and low miRNA expression are
      involved in the sensitization of ESCC to radiotherapy and prognosis of patients
      with ESCC.

PMID- 24576012
TI  - How can the IL28B polymorphisms with linkage disequilibrium affect the natural
      course of hepatitis B inversely?

PMID- 24576014
TI  - Rhabdomyolysis due to severe hypothyroidism culminating in uremic encephalopathy.

PMID- 24576013
TI  - The use of 3-dimensional ultrasound of the pelvic floor to predict recurrence
      risk after pelvic reconstructive surgery.
AB  - AIMS: Female pelvic organ prolapse is a common condition. Prolapse recurrence
      following surgical treatment is a significant clinical issue. The aim of this
      study was to determine risk factors for recurrence, attempting to improve
      clinical practice by allowing better patient selection prior to surgery. METHODS:
      This was a retrospective study utilising patient records and ultrasound volume
      imaging data sets obtained in four clinical audits following anterior
      colporrhaphy +/- mesh. Prolapse recurrence was diagnosed clinically and by
      ultrasound; findings were analysed against potential predictors. RESULTS:
      Symptomatic prolapse recurrence was demonstrated in 86 (26%), on clinical
      examination in 141 (42%) and on ultrasound in 113/334 women (34%). None of the
      tested predictors were predictive of recurrent symptoms, likely due to a lack of
      power. However, both levator avulsion and hiatal area on Valsalva were shown to
      be highly significant predictors of objective prolapse recurrence on clinical
      examination and ultrasound. CONCLUSIONS: Prolapse recurrence following surgery is
      a common complaint. The state of the patient's pelvic floor muscle seems to be
      the strongest determinant.

PMID- 24576015
TI  - Synthesis and tribological investigation of lipoyl glycerides.
AB  - Lipoyl glycerides were synthesized by enzymatic transesterification of lipoic
      acid with high-oleic sunflower oil in 2-methyl-2-butanol solvent. The synthesis
      gave a crude product mixture comprising unreacted lipoic acid, free fatty acids,
      and several lipoyl glyceride structures of varying lipoic acid substitution. A
      more purified product mixture, devoid of unreacted lipoic acid and free fatty
      acids, was obtained in 61% yield. The crude and purified product mixtures were
      thoroughly characterized and their components positively identified. The
      tribological properties of the product mixtures were further investigated using a
      variety of methods. The product mixtures displayed significantly improved
      oxidation stability, cold-flow, and extreme pressure properties over those of the
      parent high-oleic sunflower oil. The extreme pressure results for the neat
      products showed a higher weld point for the crude than for the purified mixture.
      This was attributed to differences in the chemical properties of the components
      in the two product mixtures. 

PMID- 24576016
TI  - Prevention of depression in patients with acute coronary syndrome (DECARD)
      randomized trial: effects on and by self-reported health.
AB  - AIM: Escitalopram may prevent depression following acute coronary syndrome. We
      sought to estimate the effects of escitalopram on self-reported health and to
      identify subgroups with higher efficacy. METHODS: This is a secondary analysis of
      a 12-month double-blind clinical trial randomizing non-depressed acute coronary
      syndrome patients to escitalopram (n = 120) or matching placebo (n = 120). The
      main outcomes were mean scores on Short Form 36 Health Survey (SF-36) domains,
      and diagnosis of depression was adjusted for baseline SF-36 scores. RESULTS:
      Escitalopram did not yield different SF-36 trajectories on any scale compared
      with placebo (P > 0.28). Efficacy of escitalopram may have been better among
      those scoring at least the normative score on general health perceptions (hazard
      ratio (HR) for depression 0.17 (95% confidence interval 0.02-1.42) ) or social
      functioning (HR = 0.12 (0.02-0.99) ) than in the full sample of patients (HR =
      0.20 (0.04-0.90) ), although not statistically significant. CONCLUSIONS: The SF
      36 may be too broad an outcome measure in trials or treatments that seek to
      prevent depression following acute coronary syndrome. The SF-36 may, however,
      indicate who is more likely to benefit from treatment.

PMID- 24576017
TI  - Medical mistrust, perceived discrimination, and satisfaction with health care
      among young-adult rural latinos.
AB  - PURPOSE: Little research has analyzed mistrust and discrimination influencing
      receipt of health care services among Latinos, particularly those living in rural
      areas. This study examined the associations between medical mistrust, perceived
      discrimination, and satisfaction with health care among young-adult rural
      Latinos. RESEARCH DESIGN: This cross-sectional study analyzed data from 387 young
      adult Latinos (ages 18-25) living in rural Oregon. The Behavioral Model of
      Vulnerable Populations was utilized as the theoretical framework. Correlations
      were run to assess bivariate associations among variables included in the study.
      Ordered logistic regression models evaluated the associations between medical
      mistrust, perceived discrimination, and satisfaction with health care. RESULTS:
      On average, participants used health services 4 times in the past year. Almost
      half of the participants had health insurance (46%). The majority reported that
      they were moderately (32%) or very satisfied (41%) with health care services used
      in the previous year. In multivariable models, medical mistrust and perceived
      discrimination were significantly associated with satisfaction with health care.
      CONCLUSIONS: Medical mistrust and perceived discrimination were significant
      contributors to lower satisfaction with health care among young-adult Latinos
      living in rural Oregon. Health care reform implementation, currently under way,
      provides a unique opportunity for developing evaluation systems and interventions
      toward monitoring and reducing rural Latino health care disparities.

PMID- 24576018
TI  - Radiation-sensitive novel polymeric resist materials: iterative synthesis and
      their EUV fragmentation studies.
AB  - Polymerization of (4-(methacryloyloxy)phenyl)dimethylsulfoniumtriflate (MAPDST),
      as a key monomer containing the radiation sensitive sulfonium functionality, with
      various other monomers such as methyl methacrylate (MMA), 4-carboxy styrene
      (STYCOOH), N-vinyl carbazole (NVK) in different molar ratios via free-radical
      polymerization method is described. This methodology led to the development of a
      small chemical library of six different radiation sensitive polymers for
      lithography applications. Fourier transform infrared (FT-IR) and nuclear magnetic
      resonance (NMR) spectroscopy identified the reaction products as MAPDST
      homopolymer and MAPDST-MMA, MAPDST-STYCOOH, MAPDST-NVK copolymers. Molecular
      weights were obtained from gel permeation chromatography and the decomposition
      temperature (Td) values were determined using thermogravimetric analysis (TGA).
      The effect of extreme ultraviolet (EUV) irradiation on a thin poly(MAPDST) film
      was investigated using monochromatic synchrotron excitation. These new polymeric
      materials were also exposed to electron-beam lithography (EBL) and extreme
      ultraviolet lithography (EUVL) to achieve 20-nm line patterns. 

PMID- 24576019
TI  - Ecdysone response elements in the distal promoter of the Bombyx Broad-Complex
      gene, BmBR-C.
AB  - The Bombyx mori silkworm's homologue of the Broad-Complex gene (BmBR-C) is
      transcribed from two promoters: a distal promoter (Pdist) and a proximal promoter
      (Pprox). As determined by a luciferase assay, the transcriptional activity of
      Pdist, but not Pprox, was activated by ecdysone. Further analyses using reporters
      driven by sequential deletion Pdist mutants indicated that two regions, ecdysone
      responsive element (EcRE)-D and EcRE-P, -4950 bp and -3480 bp upstream from the
      distal transcription start site, respectively, were important in the
      responsiveness of Pdist to 20-hydroxyecdysone (20E); however, no significant
      sequence similarities were found between the canonical EcRE and the EcRE-D or
      EcRE-P regions. Electrophoretic mobility shift assays showed that both the EcRE-D
      and -P sequences specifically bound to Bombyx protein(s). Sequence analyses and
      competition assays suggested that the protein(s) bound to EcRE-P might include
      components other than the ecdysone receptor (EcR), suggesting that BmBR-C
      transcription was indirectly activated by ecdysone through the EcRE-P.
      Remarkably, protein binding to the mid-region of the EcRE-D, EcRE-Db, was
      competitively inhibited by an oligonucleotide containing the Drosophila hsp27
      EcRE sequence. Furthermore, an anti-EcR antibody interfered with the formation of
      the protein-EcRE-Db complex. These results indicated that a functional Bombyx
      ecdysone receptor binds to EcRE-D and activates the expression of BmBR-C. 

PMID- 24576020
TI  - In reply.

PMID- 24576021
TI  - Digital whole slide imaging in cytology.

PMID- 24576022
TI  - Reducing laboratory costs through education-based gatekeeping.

PMID- 24576023
TI  - Topics from the Milestones Working Group, the American Board of Pathology and
      Association of Pathology Chairs (APC), and the Program Directors of Pathology
      Section of APC Working Groups in Genomics and Laboratory Management.

PMID- 24576024
TI  - The pathology milestones and the next accreditation system.
AB  - CONTEXT: In the late 1990s, the Accreditation Council for Graduate Medical
      Education developed the Outcomes Project and the 6 general competencies with the
      intent to improve the outcome of graduate medical education in the United States.
      The competencies were used as the basis for developing learning goals and
      objectives and tools to evaluate residents' performance. By the mid-2000s the
      stakeholders in resident education and the general public felt that the Outcomes
      Project had fallen short of expectations. OBJECTIVE: To develop a new evaluation
      method to track trainee progress throughout residency using benchmarks called
      milestones. A change in leadership at the Accreditation Council for Graduate
      Medical Education brought a new vision for the accreditation of training programs
      and a radically different approach to the evaluation of residents. DATA SOURCES:
      The Pathology Milestones Working Group reviewed examples of developing milestones
      in other specialties, the literature, and the Accreditation Council for Graduate
      Medical Education program requirements for pathology to develop pathology
      milestones. The pathology milestones are a set of objective descriptors for
      measuring progress in the development of competency in patient care, procedural
      skill sets, medical knowledge, practice-based learning and improvement,
      interpersonal and communication skills, professionalism, and systems-based
      practice. CONCLUSIONS: The milestones provide a national standard for evaluation
      that will be used for the assessment of all residents in Accreditation Council
      for Graduate Medical Education-accredited pathology training programs.

PMID- 24576025
TI  - Anatomic and clinical pathology boot camps: filling pathology-specific gaps in
      undergraduate medical education.
AB  - CONTEXT: The Liaison Committee on Medical Education began an initiative to change
      medical education across the United States in the early 2000s. With the explosion
      in medical science knowledge, the need arose to teach selected fundamental
      information both in a contextual and in an active learning manner. OBJECTIVE: To
      identify ways to address gaps in training and knowledge that became apparent
      following implementation of learner-centered teaching methods, with devotion of
      more time to Internet-based learning and less emphasis on face-to-face lecture
      time. There was a dramatic departure from or de-emphasis of many traditional
      courses, such as embryology, gross anatomy, microscopic anatomy, and pathology,
      to the integration of these sciences into system-based active learning courses.
      This change in medical school curricula produces a medical graduate who hopefully
      thinks differently but certainly lacks subject-specific knowledge for a variety
      of medical specialties. DATA SOURCES: Pathology residency programs have developed
      "boot camps" for the initial months of residency training both to provide the
      necessary foundation of pathology-specific medical science and to introduce basic
      skills and processes required for practice of anatomic pathology and laboratory
      medicine. The College of American Pathologists Graduate Medical Education
      Committee sent a questionnaire out on the Program Directors Section Listserv; the
      results are discussed and 3 boot camp programs are described. CONCLUSIONS: Boot
      camps have 2 purposes: (1) to teach or strengthen knowledge required to practice
      pathology and (2) to introduce basic skills and processes that will be used
      during the practitioner's career.

PMID- 24576026
TI  - A team-based approach to autopsy education: integrating anatomic and clinical
      pathology at the rotation level.
AB  - CONTEXT: Pathology residency training programs should aim to teach residents to
      think beyond the compartmentalized data of specific rotations and synthesize data
      in order to understand the whole clinical picture when interacting with
      clinicians. OBJECTIVE: To test a collaborative autopsy procedure at Montefiore
      Medical Center (Bronx, New York), linking residents and attending physicians from
      anatomic and clinical pathology in the autopsy process from the initial chart
      review to the final report. Residents consult with clinical pathology colleagues
      regarding key clinical laboratory findings during the autopsy. This new procedure
      serves multiple functions: creating a team-based, mutually beneficial educational
      experience; actively teaching consultative skills; and facilitating more in-depth
      analysis of the clinical laboratory findings in autopsies. DESIGN: An initial
      trial of the team-based autopsy system was done from November 2010 to December
      2012. Residents were then surveyed via questionnaire to evaluate the frequency
      and perceived usefulness of clinical pathology autopsy consultations. RESULTS:
      Senior residents were the most frequent users of clinical pathology autopsy
      consultation. The most frequently consulted services were microbiology and
      chemistry. Eighty-nine percent of the residents found the clinical pathology
      consultation to be useful in arriving at a final diagnosis and clinicopathologic
      correlation. CONCLUSION: The team-based autopsy is a novel approach to
      integration of anatomic and clinical pathology curricula at the rotation level.
      Residents using this approach develop a more holistic approach to pathology,
      better preparing them for meaningful consultative interaction with clinicians.
      This paradigm shift in training positions us to better serve in our increasing
      role as arbiters of outcomes measures in accountable care organizations.

PMID- 24576027
TI  - National standards in pathology education: developing competencies for integrated
      medical school curricula.
AB  - CONTEXT: Medical school education has evolved from department-specific
      memorization of facts to an integrated curriculum presenting knowledge in a
      contextual manner across traditional disciplines, integrating information,
      improving retention, and facilitating application to clinical practice.
      Integration occurs throughout medical school using live data-sharing
      technologies, thereby providing the student with a framework for lifelong active
      learning. Incorporation of educational teams during medical school prepares
      students for team-based patient care, which is also required for pay-for
      performance models used in accountable care organizations. OBJECTIVE: To develop
      learning objectives for teaching pathology to medical students. Given the rapid
      expansion of basic science knowledge of human development, normal function, and
      pathobiology, it is neither possible nor desirable for faculty to teach, and
      students to retain, this vast amount of information. Courses teaching the
      essentials in context and engaging students in the learning process enable them
      to become lifelong learners. An appreciation of pathobiology and the role of
      laboratory medicine underlies the modern practice of medicine. As such, all
      medical students need to acquire 3 basic competencies in pathology: an
      understanding of disease mechanisms, integration of mechanisms into organ system
      pathology, and application of pathobiology to diagnostic medicine. DESIGN: We
      propose the development of 3 specific competencies in pathology to be implemented
      nationwide, aimed at disease mechanisms/processes, organ system pathology, and
      application to diagnostic medicine. Each competency will include learning
      objectives and a means to assess acquisition, integration, and application of
      knowledge. The learning objectives are designed to be a living document managed
      (curated) by a group of pathologists representing Liaison Committee on Medical
      Education-accredited medical schools nationally. CONCLUSIONS: Development of a
      coherent set of learning objectives will assist medical students nationally to
      gain the basic competencies in pathology necessary for clinical practice. Having
      national standards for competencies preserves schools' independence in specific
      curriculum design while assuring all students meet the evolving needs of medical
      practice.

PMID- 24576028
TI  - Current issues in gynecologic pathology.

PMID- 24576029
TI  - Endometrial carcinoma in women aged 40 years and younger.
AB  - CONTEXT: Endometrial carcinoma is a disease of older postmenopausal women, and is
      relatively uncommon in patients younger than 40 years. Endometrial carcinomas in
      this age group may be familial, associated with Lynch syndrome, or sporadic.
      OBJECTIVES: To present our current knowledge of endometrial carcinomas in women
      younger than 40 years. DATA SOURCES: The review is based on previously published
      articles on this topic. CONCLUSIONS: Most endometrial carcinomas that occur in
      this age group are associated with estrogen excess. They are usually low-grade
      endometrioid carcinomas that present at low stages and are associated with
      favorable clinical outcomes. Tumors associated with mismatch repair abnormalities
      and Lynch syndrome appear to be distinct, with worse prognostic factors and,
      possibly, clinical behavior. Conservative hormonal therapy and ovarian
      conservation are reasonable considerations in the management of these young
      patients, but carry the risk of tumor progression, recurrence, and an occult
      synchronous or metachronous ovarian carcinoma.

PMID- 24576030
TI  - HER2/neu in Endometrial Cancer: A Promising Therapeutic Target With Diagnostic
      Challenges.
AB  - CONTEXT: In the era of targeted cancer therapy, there is growing interest in
      developing novel therapeutic strategies against endometrial carcinoma, especially
      its most biologically aggressive variant, serous adenocarcinoma. Several
      publications have demonstrated that a significant proportion of uterine serous
      carcinomas show HER2 overexpression and/or amplification, suggesting that HER2
      may be a promising therapeutic target. Case reports have already shown clinical
      response to trastuzumab, a humanized monoclonal immunoglobulin (Ig) G1 antibody
      against HER2, and patients are currently being enrolled in a multi-institutional
      prospective randomized trial to evaluate the therapeutic efficacy of trastuzumab.
      OBJECTIVE: To review current data on HER2 testing and targeted therapy against
      HER2/neu in endometrial carcinoma. DATA SOURCES: Review of the literature and
      personal experience of the authors. CONCLUSIONS: Parallel to the clinical
      studies, there is a need to develop standardized criteria for HER2 testing in
      endometrial carcinoma that reflect the unique biological and pathogenetic
      features of these tumors and correlate with clinical response to therapy. This
      article presents a comprehensive review of the current state of HER2-based
      therapy and HER2 testing in endometrial carcinoma.

PMID- 24576031
TI  - Germ cell tumors of the ovary: an update.
AB  - CONTEXT: The field of ovarian germ cell tumors (OGCTs) has remained relatively
      unchanged in the last 2 decades. However, the introduction of new stem cell
      pluripotency markers has provided a new understanding into the identification and
      taxonomy of OGCT types. New data have provided new insights into unusual teratoma
      associated autoimmune disorders and the origin of gliomatosis peritonei.
      OBJECTIVE: To review the impact of new pluripotency markers in the diagnosis of
      malignant OGCT (MOGCT) and analyze new nomenclature proposals and
      clinicopathologic entities. DATA SOURCES: Ovarian germ cell tumors from routine
      material and expert consultation files at San Cecilio University Hospital,
      Granada, Spain, and the relevant literature were reviewed. CONCLUSIONS: Although
      a correct diagnosis of MOGCT can often be made with histologic and classic
      immunohistochemical studies, the new immunohistochemical pluripotency markers
      give higher diagnostic accuracy. Germ cell tumors represent a caricature of the
      phases of normal embryonic differentiation from primordial germ and stem cells to
      extraembryonal and somatic tissue differentiation. Since every stage of
      differentiation and its related tumor type exhibit characteristic markers, the
      analysis of their expression facilitates tumor typing, thus complementing the use
      of classic antibodies. They also allow a more precise evaluation of the degree of
      immaturity in teratoma. The new term, primitive endodermal tumors, simplifies the
      understanding of the complex histology of the yolk sac tumor group, as this
      terminology encompasses its multiple endodermal differentiations. Recently
      described autoimmune encephalitis due to antibodies against the N-methyl-d
      aspartate receptor has become the most frequent autoimmune disorder associated
      with ovarian teratoma.

PMID- 24576032
TI  - Summary of microsatellite instability test results from laboratories
      participating in proficiency surveys: proficiency survey results from 2005 to
      2012.
AB  - CONTEXT: The College of American Pathologists surveys are the largest laboratory
      peer comparison programs in the world. These programs allow laboratories to
      regularly evaluate their performance and improve the accuracy of the patient test
      results they provide. Proficiency testing is offered twice a year to laboratories
      performing microsatellite instability testing. These surveys are designed to
      emulate clinical practice, and some surveys have more challenging cases to
      encourage the refinement of laboratory practices. OBJECTIVE: This report
      summarizes the results and trends in microsatellite instability proficiency
      testing from participating laboratories from the inception of the program in 2005
      through 2012. DESIGN: We compiled and analyzed data for 16 surveys of
      microsatellite instability proficiency testing during 2005 to 2012. RESULTS: The
      number of laboratories participating in the microsatellite instability survey has
      more than doubled from 42 to 104 during the 8 years analyzed. An average of 95.4%
      of the laboratories correctly classified each of the survey test samples from the
      2005A through 2012B proficiency challenges. In the 2011B survey, a lower
      percentage of laboratories (78.4%) correctly classified the specimen, possibly
      because of overlooking subtle changes of microsatellite instability and/or
      failing to enrich the tumor content of the specimen to meet the limit of
      detection of their assay. CONCLUSIONS: In general, laboratories performed well in
      microsatellite instability testing. This testing will continue to be important in
      screening patients with colorectal and other cancers for Lynch syndrome and
      guiding the management of patients with sporadic colorectal cancer.

PMID- 24576033
TI  - MYB gene abnormalities t(6;9) in adenoid cystic carcinoma fine-needle aspiration
      biopsy using fluorescence in situ hybridization.
AB  - CONTEXT: Fine-needle aspiration (FNA) biopsy of salivary gland neoplasms can have
      a variety of overlapping appearances. Basaloid neoplasms can be a diagnostic
      challenge, and FNA cytomorphology alone cannot always provide a definitive
      diagnosis. OBJECTIVE: To examine the incidence and potential utility of detecting
      a MYB translocation by fluorescence in situ hybridization (FISH) in adenoid
      cystic carcinomas (AdCCs) and pleomorphic adenoma FNA smears with known surgical
      outcomes. DESIGN: Patients who underwent FNA biopsy for surgically confirmed
      AdCCs and pleomorphic adenomas were identified. Fluorescence in situ
      hybridization, using commercially available fluorescent-labeled probes,
      hybridizing to MYB-telomeric and MYB-centromeric, was used to identify the MYB
      gene and to evaluate it for abnormalities and translocation. Using a fluorescent
      microscope, 4',6-diamidino-2-phenylindole (DAPI)-stained, nonoverlapping cells
      were counted, and 10% or greater abnormal cells were considered positive.
      RESULTS: The 10 AdCC and 13 pleomorphic adenoma FNA cases had FISH evaluations
      performed; 50% (5 of 10) of the AdCC cases showed a MYB abnormality by FISH; 40%
      (4 of 10) AdCCs showed a positive break-apart signal in most cells (48%-84%). One
      case (10%) of AdCC showed a trisomy MYB signal pattern without the break-apart
      translocation pattern. Of the 13 pleomorphic adenomas, none (0%) of the cases
      showed a MYB translocation or abnormality by FISH. MYB FISH abnormalities showed
      a 100% positive predictive value, 50% sensitivity, and 100% specificity, when
      differentiating AdCC from pleomorphic adenoma. CONCLUSIONS: MYB gene
      abnormalities were present in 50% (5 of 10) of the AdCC cases. This corresponds
      to the reported prevalence in formalin-fixed, paraffin-embedded tissue for AdCC
      surgical resections. Using FISH testing for detecting MYB gene abnormalities in
      the salivary gland of FNA biopsies has the potential to provide additional,
      helpful ancillary information in diagnosing AdCC.

PMID- 24576034
TI  - Five important advances in hematopathology.
AB  - CONTEXT: Hematopathology is a dynamic field that has always been on the frontier
      of clinical research within the scope of pathology. Several recent developments
      in hematopathology will likely affect its practice clinically. OBJECTIVE: To
      review 5 important recent advances in hematopathology: (1) detection and
      prognostic implication of MYC in diffuse large B-cell lymphomas, (2) determining
      origin and prognosis through immunoglobulin gene usage in mature B-cell
      neoplasms, (3)detecting minimal residual disease in multiple myeloma, (4) using
      genome-wide analysis in myelodysplastic syndromes, and (5) employing whole-genome
      sequencing in acute myeloid leukemias. DATA SOURCES: Literature review and the
      authors' experiences in an academic center. CONCLUSIONS: These advances will
      bring hematopathology into a new molecular era and help us to better understand
      the molecular, pathologic mechanisms of lymphomas, leukemias, myelomas, and
      myelodysplastic syndromes. They will help us to identify diagnostic and
      prognostic markers and eventually provide new therapeutic targets and treatments
      for these diseases.

PMID- 24576035
TI  - The Prince Edward Island-Mayo Clinic connection: Malcolm B. Dockerty and Lewis B.
      Woolner.
AB  - CONTEXT: Malcolm B. Dockerty and Lewis B. Woolner, 2 preeminent mid-20th-century
      surgical pathologists, spent their entire careers at the Mayo Clinic. Both were
      raised in poverty on potato farms only 49 miles apart in Canada's smallest
      province (Prince Edward Island); both were educated in 1-room schools and
      graduated as gold medalists from Prince Edward Island's only college and then
      from Maritime Canada's only medical school; both then trained at the Mayo Clinic.
      OBJECTIVE: To explore the lives and accomplishments of these 2 important surgical
      pathologists. DESIGN: Standard historiographic methods were used to explore
      primary and secondary historical sources. RESULTS: Both became world-renowned
      general surgical pathologists, one developing subspecialty expertise in
      gynecologic pathology and the other in cytopathology, pulmonary pathology, and
      thyroid/parathyroid pathology. Both were prolific authors with h-indices higher
      than 40, and between them, they published more than 750 peer-reviewed papers and
      book chapters. As educators, they trained hundreds of pathology and surgery
      residents/fellows who disseminated their knowledge around the world. Both were
      fascinated by poetry from childhood and could quote the classics from memory. One
      wrote poetry throughout his entire life and even used it to teach pathology and
      serve as his memoir; the other strongly preferred the classics and in jest called
      his colleague "a (minor) poet." Both received postretirement honorary doctorates
      from their alma maters. Dockerty died in 1987; Woolner celebrates his 100th
      birthday on November 17, 2013. CONCLUSION: Every pathologist should know of these
      2 pioneering surgical pathologists.

PMID- 24576036
TI  - Gastroesophageal heterotopia and HER2/neu overexpression in an adenocarcinoma
      arising from a small bowel duplication.
AB  - Small bowel duplications are congenital structures commonly lined by heterotopic
      gastric or pancreatic mucosa. Though benign in children, small bowel duplications
      have the potential for malignant degeneration in adulthood. Here, we present the
      first reported case of metastatic adenocarcinoma arising from a small bowel
      duplication lined by gastroesophageal mucosa. The cancer demonstrated
      overexpression of the HER2/neu oncoprotein and amplification of the HER2/neu
      gene. This represents the only report of HER2 overexpression in this type of
      lesion. The patient is being treated with traditional chemotherapeutic agents in
      addition to monoclonal antibody therapy directed at the HER2 protein, and has
      demonstrated a clinical benefit from treatment. This case demonstrates that the
      anatomic location of a mass may be distinct from its biological origin, and this
      difference may have important practical implications for diagnostic testing and
      treatment. 

PMID- 24576037
TI  - Mullerianosis of the urinary bladder: a rare tumorlike lesion.
AB  - Mullerianosis was first described as a rare entity consisting of an admixture of
      cervical, tubaric, or endometrial epithelium within the lamina propria and
      muscularis propria of the urinary bladder. This lesion occurs mainly in the dome
      or posterior wall of the urinary bladder in women of fertile age. Its clinical
      presentation is characterized by hematuria, pelvic pain, and dysuria, nonspecific
      symptoms that are related to the responsiveness of mullerian glands to hormonal
      stimuli. The major interest of mullerianosis resides in its similarity, from
      clinical, cytologic, and histologic viewpoints, to more threatening conditions,
      such as neoplasias. The clinical context and the identification of periglandular
      endometrial stroma at histologic examination with conventional hematoxylin-eosin
      stain, as well as the immunohistochemical demonstration of estrogen and
      progesterone receptors in the glands, are of diagnostic utility in the
      differential diagnosis. Mullerianosis may be responsive to gonadotropin-releasing
      hormone agonists. Surgical resection may be justified in the case of clinical
      symptoms refractory to hormone therapy. 

PMID- 24576040
TI  - Quantitative elastography of the uterine cervix requires a reference material
      Reply.

PMID- 24576041
TI  - Visualising and modelling changes in categorical variables in longitudinal
      studies.
AB  - BACKGROUND: Graphical techniques can provide visually compelling insights into
      complex data patterns. In this paper we present a type of lasagne plot showing
      changes in categorical variables for participants measured at regular intervals
      over time and propose statistical models to estimate distributions of marginal
      and transitional probabilities. METHODS: The plot uses stacked bars to show the
      distribution of categorical variables at each time interval, with different
      colours to depict different categories and changes in colours showing
      trajectories of participants over time. The models are based on nominal logistic
      regression which is appropriate for both ordinal and nominal categorical
      variables. To illustrate the plots and models we analyse data on smoking status,
      body mass index (BMI) and physical activity level from a longitudinal study on
      women's health. To estimate marginal distributions we fit survey wave as an
      explanatory variable whereas for transitional distributions we fit status of
      participants (e.g. smoking status) at previous surveys. RESULTS: For the
      illustrative data the marginal models showed BMI increasing, physical activity
      decreasing and smoking decreasing linearly over time at the population level. The
      plots and transition models showed smoking status to be highly predictable for
      individuals whereas BMI was only moderately predictable and physical activity was
      virtually unpredictable. Most of the predictive power was obtained from
      participant status at the previous survey. Predicted probabilities from the
      models mostly agreed with observed probabilities indicating adequate goodness-of
      fit. CONCLUSIONS: The proposed form of lasagne plot provides a simple visual aid
      to show transitions in categorical variables over time in longitudinal studies.
      The suggested models complement the plot and allow formal testing and estimation
      of marginal and transitional distributions. These simple tools can provide
      valuable insights into categorical data on individuals measured at regular
      intervals over time.

PMID- 24576038
TI  - The prostaglandin f2alpha analog fluprostenol attenuates the fibrotic effects of
      connective tissue growth factor on human trabecular meshwork cells.
AB  - Abstract Purpose: The trabecular meshwork (TM) outflow pathways of the aqueous
      humor show an increase in extracellular matrix in patients with primary open
      angle glaucoma (POAG). The increase in TM extracellular matrix appears to be
      caused by transforming growth factor-beta signaling and its downstream mediator
      connective-tissue growth factor (CTGF). Here we studied whether treatment with
      the prostaglandin F2alpha analog fluprostenol modulates the CTGF-mediated
      increase of the TM extracellular matrix. METHODS: Human TM cells from 3 different
      donors were treated with CTGF (50 ng/mL) and/or fluprostenol (10(-6) M and 10(-7)
      M) and were analyzed by real-time reverse transcription polymerase chain reaction
      and Western blotting. Cell supernatants of the treated cells were analyzed by
      zymography. RESULTS: Treatment with CTGF induced the expression and synthesis of
      CTGF, fibronectin, collagen type IV and VI, while treatment with fluprostenol
      alone had no effects. The effects of CTGF were blocked by 1-h pretreatment with
      fluprostenol in a dose-dependent manner. Treatment with fluprostenol or combined
      fluprostenol/CTGF induced the activity of matrix metalloproteinase 2 (MMP2) in TM
      cells, whereas treatment with CTGF alone had no effects on MMP2 activity.
      CONCLUSIONS: Fluprostenol blocks the fibrotic effects of CTGF on human TM cells
      and increases the activity of MMP2. Both effects have the distinct potential to
      attenuate a CTGF-mediated increase in TM extracellular matrix in patients with
      POAG and any effects on TM outflow resistance that may result from that.

PMID- 24576042
TI  - Enhanced physical health screening for people with severe mental illness in Hong
      Kong: results from a one-year prospective case series study.
AB  - BACKGROUND: People with severe mental illness have significantly poorer physical
      health compared to the general population; previous health screening studies
      conducted outside Asian countries have demonstrated the potential in addressing
      this issue. This case series aimed to explore the effects and utility of
      integrating an enhanced physical health screening programme for community
      dwelling patients with severe mental illness into routine clinical practice in
      Hong Kong. METHOD: This study utilises a consecutive prospective case series
      design. The serious mental illness Health Improvement Profile (HIP) was used as a
      screening tool at baseline and repeated at 12 months follow-up. RESULTS: A total
      of 148 community-based patients with severe mental illness completed the study.
      At one year follow-up analysis showed a significant improvement in self-reported
      levels of exercise and a reduction in the numbers of patients prescribed
      medications for diabetes However, mean waist circumference increased at follow
      up. In addition to the statistically significant results some general trends were
      observed, including: a lack of deterioration in most areas of cardiovascular
      risk; a reduction in medicines prescribed for physical health problems; and
      general improvements in health behaviours over the 12 month period. CONCLUSIONS:
      The findings demonstrate that using the HIP is feasible and acceptable in Hong
      Kong. The results of the enhanced physical health-screening programme are
      promising, but require further testing using a randomised controlled trial design
      in order to more confidently attribute the improvements in well-being and health
      behaviours to the HIP. TRIAL REGISTRATION:  CLINICAL TRIAL REGISTRATION NUMBER:
      ISRCTN12582470.

PMID- 24576044
TI  - Fatal child abuse presenting with multiple vertebral and vascular trauma.
AB  - This case study involves the unexplained death of a previously healthy 30-month
      old child. Reportedly, she was found unresponsive by her foster father following
      a 2-hour nap. She was transported to the hospital and died in the emergency room
      of unknown causes. Blood drawn in the ER showed hemoglobin of 4.3 mg/dL.
      Postmortem skeletal survey, magnetic resonance imaging (MRI) of the brain, and
      retinal examinations were negative. The medical examiner assumed jurisdiction of
      the body. The autopsy showed massive retroperitoneal hemorrhage, transections of
      the abdominal aorta, and inferior vena cava, and complete tears of the anterior
      longitudinal ligament of the spine at C5/C6 and L1/L2 with diastases of the
      vertebral bodies at the corresponding intervertebral disk spaces. The case is
      believed to be extraordinary due to both the extent of injury that does not match
      the reported history and the mechanism of vertebral and vascular injuries. 

PMID- 24576045
TI  - Prominent cervical mucous and its impact on cervical length measurement: findings
      of a national survey.
AB  - INTRODUCTION: Cervical length measurement by transvaginal scanning (TVS) has been
      proposed by some as a universal screening test for preterm labour. The presence
      of prominent cervical mucous may affect assessment of the cervix; however, the
      exact technique to measure the cervix when there is prominent mucous or
      funnelling has not been described. We evaluated the level of agreement in
      cervical length measurements amongst Australian specialists and sonographers
      reporting on cervical assessment using an online survey. METHODS: We conducted an
      online survey with 11 images of the cervix to assess how obstetric sonographers
      and sonologists report on the cervix when there is prominent mucous or
      funnelling. They were asked five questions about the image of the cervix. A kappa
      coefficient was calculated from the responses. RESULTS: We had 151 complete
      responses to the online survey. For the images which showed funnelling or
      prominent cervical mucous, there was little agreement regarding the cervix being
      open or closed and regards the location of the internal os. The Kappa coefficient
      was 0.22 indicating a low level of agreement for the location of the internal os.
      CONCLUSION: There is lack of agreement amongst Australian specialists and
      sonographers reporting on cervical assessment when there is prominent mucous or
      funnelling seen in the cervix. We propose a method to standardise reporting on
      the cervix incorporating the chorioamniotic membrane for the identification of
      the inner cervical os when there is prominent mucous or funnelling.

PMID- 24576043
TI  - The basal transcription machinery as a target for cancer therapy.
AB  - General transcription is required for the growth and survival of all living
      cells. However, tumor cells require extraordinary levels of transcription,
      including the transcription of ribosomal RNA genes by RNA polymerase I (RNPI) and
      mRNA by RNA polymerase II (RNPII). In fact, cancer cells have mutations that
      directly enhance transcription and are frequently required for cancer
      transformation. For example, the recent discovery that MYC enhances the
      transcription of the majority genes in the genome correlates with the fact that
      several transcription interfering drugs preferentially kill cancer cells. In
      recent years, advances in the mechanistic studies of the basal transcription
      machinery and the discovery of drugs that interfere with multiple components of
      transcription are being used to combat cancer. For example, drugs such as
      triptolide that targets the general transcription factors TFIIH and JQ1 to
      inhibit BRD4 are administered to target the high proliferative rate of cancer
      cells. Given the importance of finding new strategies to preferentially sensitize
      tumor cells, this review primarily focuses on several transcription inhibitory
      drugs to demonstrate that the basal transcription machinery constitutes a
      potential target for the design of novel cancer drugs. We highlight the drugs'
      mechanisms for interfering with tumor cell survival, their importance in cancer
      treatment and the challenges of clinical application. 

PMID- 24576046
TI  - Noninvasive differentiation of simple steatosis and steatohepatitis by using
      gadoxetic acid-enhanced MR imaging in patients with nonalcoholic fatty liver
      disease: a proof-of-concept study.
AB  - PURPOSE: To determine whether gadoxetic acid-enhanced magnetic resonance (MR)
      imaging can be used to distinguish between simple steatosis and nonalcoholic
      steatohepatitis (NASH) in patients with nonalcoholic fatty liver disease (NAFLD),
      defined according to the steatosis activity and fibrosis (SAF) scoring system,
      which is based on the semiquantitative scoring of steatosis activity and liver
      fibrosis. MATERIALS AND METHODS: The local institutional review committee
      approved this study and waived written informed consent. This was a retrospective
      study of gadoxetic acid-enhanced 3-T MR imaging performed in 81 patients with
      NAFLD (45 men [56%]; mean age, 56 years; range, 25-78 years). The MR images were
      analyzed by using the relative enhancement (the ratio of signal intensities of
      the liver parenchyma before and 20 minutes after intravenous administration of
      gadoxetic acid). Univariate and multiple regression analyses were applied to
      identify variables associated with relative enhancement measurements. The ability
      of relative enhancement to allow differentiation between simple steatosis and
      NASH was assessed by using area under the receiver operating characteristic (ROC)
      curve analysis. RESULTS: Relative enhancement negatively correlated with the
      degree of lobular inflammation (r = -0.59, P < .0001), ballooning (r = -0.44, P <
      .0001), and fibrosis (r = -0.59, P <= .0001), but not with steatosis (r = -0.16,
      P = .15). Patients with NASH had a significantly lower relative liver enhancement
      (0.82 +/- 0.22) than those with simple steatosis (1.39 +/- 0.52) (P < .001).
      Relative enhancement measurements performed well in the differentiation between
      simple steatosis and NASH, with an area under the ROC curve of 0.85 (95%
      confidence interval: 0.75, 0.91) (cutoff = 1.24, sensitivity = 97%, specificity =
      63%). CONCLUSION: Gadoxetic acid relative enhancement was significantly lower in
      patients with NASH than in patients with simple steatosis, but further
      prospective studies are warranted.

PMID- 24576048
TI  - Poster presentation abstracts.

PMID- 24576049
TI  - Platform presentation abstracts.

PMID- 24576047
TI  - Potential predictors of side-branch occlusion in bifurcation lesions after
      percutaneous coronary intervention: a coronary CT angiography study.
AB  - PURPOSE: To identify potential predictors of side-branch occlusion after main
      vessel (artery) stent implantation in bifurcation lesions by using coronary
      computed tomography (CT) angiography. MATERIALS AND METHODS: This retrospective
      study was approved by the institutional review board; informed consent was
      waived. Sixty-five patients with de novo bifurcation lesions underwent coronary
      CT angiography before percutaneous coronary intervention. By defining side-branch
      occlusion as Thrombolysis in Myocardial Infarction flow grade 2 or lower,
      coronary CT angiography plaque characteristics associated with side-branch
      occlusion (ie, plaque morphology and composition) were analyzed. A multiple
      logistic regression analysis was undertaken to determine independent potential
      predictors of side-branch occlusion. RESULTS: Of 65 patients enrolled, 12
      patients (18%) had side-branch occlusion after main-vessel stent implantation.
      Patients with side-branch occlusion had larger mean plaque thickness in the side
      branch side of the proximal main vessel (2.29 mm +/- 1.87 [standard deviation] vs
      1.29 mm +/- 1.43, P = .043), larger plaque thickness in the noncarinal side of
      the side branch (1.43 mm +/- 1.18 vs 0.51 mm +/- 0.65, P < .001), smaller side
      branch lumen diameter (1.24 mm +/- 0.74 vs 1.87 mm +/- 0.71, P = .007), and
      higher diameter stenosis (50.9% +/- 24.0 vs 25.5% +/- 25.3, P = .002) compared
      with those without side-branch occlusion. The cutoff value of proximal main
      vessel plaque thickness was 2.7 mm (area under the curve [AUC], 0.67; 95%
      confidence interval [CI]: 0.48, 0.86) and of side-branch-diameter stenosis was
      40% (AUC, 0.79; 95% CI: 0.67, 0.92). Lesions with plaque thickness in proximal
      main vessel greater than 2.7 mm and side-branch-diameter stenosis greater than
      40% were associated with a 5.6-fold and 6.2-fold, respectively, increased risk of
      side-branch occlusion. CONCLUSION: Potential coronary CT angiography predictors
      of side-branch occlusion in bifurcation lesions are plaque thickness in the side
      branch side of the proximal main vessel, plaque thickness in the noncarinal side
      of the side branch, side-branch lumen diameter, and side-branch-diameter
      stenosis. These potential predictors might guide operators planning the optimal
      strategy for treating bifurcation lesions.

PMID- 24576051
TI  - Association of sequence polymorphism in the mitochondrial D-loop with chronic
      kidney disease.
AB  - BACKGROUND: The mitochondrial displacement loop (D-loop) is known to accumulate
      mutations and single nucleotide polymorphisms (SNPs) at a higher frequency than
      other regions of mitochondrial DNA (mtDNA). METHODS: This is a case-control
      study. We sequenced SNPs in the D-loop of mtDNA and investigated their
      association with the risk of chronic kidney disease (CKD). RESULTS: A total of
      144 SNPs referring to the positions of the Revised Cambridge Reference Sequence
      (rCRS) for mitochondrial genome were identified in a case-control study. The
      minor alleles of nucleotides 73G, 146C, 150T, 194T, 195C and 310C were associated
      with an increased risk for CKD patients. CONCLUSION: Analysis of genetic
      polymorphisms in the mitochondrial D-loop can help identify the people who are at
      a high risk of developing chronic kidney disease. These SNPs can be considered as
      potential predictors for CKD.

PMID- 24576050
TI  - In vivo bioluminescent tracking of mesenchymal stem cells within large hydrogel
      constructs.
AB  - The use of multicomponent scaffolds for cell implantation has necessitated
      sophisticated techniques for tracking of cell survival in vivo. Bioluminescent
      imaging (BLI) has emerged as a noninvasive tool for evaluating the therapeutic
      potential of cell-based tissue engineering strategies. However, the ability to
      use BLI measurements to longitudinally assess large 3D cellular constructs in
      vivo and the effects of potential confounding factors are poorly understood. In
      this study, luciferase-expressing human mesenchymal stem cells (hMSCs) were
      delivered subcutaneously within agarose and RGD-functionalized alginate hydrogel
      vehicles to investigate the impact of construct composition and tissue formation
      on BLI signal. Results showed that alginate constructs exhibited twofold greater
      BLI counts than agarose constructs at comparable hMSC doses. However, each
      hydrogel type produced a linear correlation between BLI counts and live cell
      number, indicating that within a given material, relative differences in cell
      number could be accurately assessed at early time points. The survival efficiency
      of delivered hMSCs was highest for the lower cell doses embedded within alginate
      matrix. BLI signal remained predictive of live cell number through 1 week in
      vivo, although the strength of correlation decreased over time. Irrespective of
      hydrogel type or initial hMSC seeding dose, all constructs demonstrated a degree
      of vascularization and development of a fibrotic capsule after 1 week. Formation
      of tissue within and adjacent to the constructs was accompanied by an attenuation
      of BLI signal during the initial period of the image acquisition time-frame. In
      alginate constructs only, greater vessel volume led to a delayed rise in BLI
      signal following luciferin delivery. This study identified vascular and fibrotic
      tissue ingrowth as potential confounding variables for longitudinal BLI studies.
      Further investigation into the complexities of noninvasive BLI data acquisition
      from multicomponent constructs, following implantation and subsequent tissue
      formation, is warranted. 

PMID- 24576052
TI  - Albumin fusion prolongs the antioxidant and anti-inflammatory activities of
      thioredoxin in mice with acetaminophen-induced hepatitis.
AB  - Overdoses of acetaminophen (APAP) are a major cause of acute liver failure. N
      Acetylcysteine (NAC) is the standard therapy for patients with such an overdose
      because oxidative stress plays an important role in the pathogenesis of APAP
      induced hepatitis. However, NAC is not sufficiently efficacious. We previously
      developed a recombinant human serum albumin (HSA)-thioredoxin 1 (Trx) fusion
      protein (HSA-Trx), designed to overcome the unfavorable pharmacokinetic and short
      pharmacological properties of Trx, an endogenous protein with antioxidative and
      anti-inflammatory properties. In this study, we investigated the therapeutic
      impact of HSA-Trx in mice with APAP-induced hepatitis. The systemic
      administration of HSA-Trx significantly improved the survival rate of mice
      treated with a lethal dose of APAP compared with saline. HSA-Trx strongly
      attenuated plasma transaminases in APAP-induced hepatitis mice compared with HSA
      or Trx, components of the fusion protein. HSA-Trx also markedly caused a
      diminution in the histopathological features of hepatic injuries and the number
      of apoptosis-positive hepatic cells. In addition, an evaluation of oxidative
      stress markers and plasma cytokine and chemokine levels clearly showed that HSA
      Trx significantly improved the breakdown of hepatic redox conditions and
      inflammation caused by the APAP treatment. HSA-Trx also significantly decreased
      oxidative and nitrosative/nitrative stress induced by SIN-1 in vitro. Finally,
      HSA-Trx, but not the NAC treatment at 4 h after APAP injection, significantly
      inhibited the elevation in plasma transaminase levels. In conclusion, the
      findings suggest that HSA-Trx has considerable potential for use as a novel
      therapeutic agent for APAP-induced hepatitis, due to its long-lasting
      antioxidative and anti-inflammatory effects. 

PMID- 24576053
TI  - Perceived correlates of domain-specific physical activity in rural adults in the
      Midwest.
AB  - PURPOSE: In response to calls for more specificity when measuring physical
      activity, this study examined perceived correlates of this behavior in rural
      adults separately by the domain in which this behavior occurs (ie, home care,
      work, active living, and sport). METHODS: A cross-sectional survey was completed
      by 407 adults from 2 rural towns in the Midwest. The questionnaire assessed the
      perceived social and physical environment, including neighborhood
      characteristics, as well as barriers to being active. The Kaiser Physical
      Activity Survey captured domain-specific activity levels. The response rate was
      25%. Multiple regression analyses were conducted to examine the associations
      between social and physical environment factors and domain-specific physical
      activity. FINDINGS: Having a favorable attitude toward using government funds for
      exercise and activity-friendly neighborhood characteristic were positively
      associated with active living. Friends encouraging exercise was positively
      associated with participation in sport. Barriers were inversely associated with
      active living and sport. Total physical activity was positively associated with
      workplace incentives for exercise, favorable policy attitudes toward supporting
      physical education in schools and supporting the use of government funds for
      biking trails, and it was inversely associated with barriers. There were no
      factors associated with physical activity in the domains of work or home care.
      CONCLUSIONS: Correlates of physical activity are unique to the domain in which
      this behavior occurs. Programs to increase physical activity in rural adults
      should target policy attitudes, neighborhood characteristics, and social support
      from friends while also working to decrease personal barriers to exercise.

PMID- 24576054
TI  - Association between low blood glucose increase during glucose tolerance tests in
      pregnancy and impaired fetal growth.
AB  - OBJECTIVE: To evaluate how different levels of increase in maternal blood glucose
      from a fasting state to 2 h after an oral glucose challenge in late pregnancy are
      associated with fetal growth, with special emphasis on those with a low increase.
      DESIGN: Prospective cohort study. SUBJECTS: We followed 855 women, of whom 70%
      had an increased risk for carrying lighter babies. STUDY DESIGN AND METHODS:
      Ultrasound was used to estimate fetal growth in gestational weeks 25, 33 and 37.
      In week 37 the women had a 75-g oral glucose tolerance test, and fasting and 2-h
      capillary glucose values were recorded with the difference between these two
      called delta (?) glucose. Three groups were constructed from the ? glucose
      distribution: Low below the 10th centile; Medium between the 10th and 90th
      centiles; and High above the 90th centile. Missing data were imputed. Linear and
      Poisson regression models were applied. OUTCOME MEASURES: Estimated fetal weight,
      percent deviation from expected fetal weight and anthropometric measures at
      birth. RESULTS: The Low group carried the lightest fetuses and the High group the
      heaviest. The fetal growth in the Low group deviated increasingly more in a
      negative direction from week 25 to 37 than in the other groups. CONCLUSION: In a
      high-risk population, a positive relation between ? glucose and fetal growth was
      found. The Low group demonstrated impaired growth. More attention should be paid
      to pregnant women with an insufficient increase in glucose after a glucose
      challenge. Future studies should challenge our findings in high-risk and low-risk
      populations.

PMID- 24576055
TI  - Reappraisal of serum alpha-foetoprotein as a surveillance test for hepatocellular
      carcinoma during entecavir treatment.
AB  - BACKGROUND & AIMS: The aim of this study was to re-evaluate the diagnostic
      performance of alpha-foetoprotein (AFP) as a surveillance test for hepatocellular
      carcinoma (HCC) in patients with hepatitis B virus-related chronic liver disease
      who were treated with entecavir (ETV). METHODS: Between January 2007 and August
      2012, we analysed 373 treatment-naive patients with HBV-related chronic hepatitis
      (n = 229) or cirrhosis (n = 144) who were candidates for surveillance test, and
      were treated with ETV (0.5 mg/day) for longer than 12 months. To minimize the
      effect of AFP elevation caused by hepatitis activity, serum AFP levels were
      measured 12 months after the initiation of ETV treatment. RESULTS: Hepatocellular
      carcinoma developed in 28 patients (7.5%) during a median follow-up period of
      48.0 months (IQR = 40.5-57.3 months). The area under the receiver operating
      characteristic curve for AFP was 0.71 (95% CI = 0.59-0.84). The optimal AFP cut
      off value was 13 ng/ml, leading to a sensitivity of 50.0%, specificity of 98.8%,
      positive predictive value of 77.8% and negative predictive value of 96.1%. In
      multivariate Cox analysis, an older age, the presence of cirrhosis and AFP levels
      of >=20 ng/ml at 12 months after treatment were found to be significantly
      associated with an increased incidence of HCC. CONCLUSIONS: The role of serum AFP
      as a surveillance test should be re-evaluated in patients with HBV-related
      chronic liver diseases who were treated with antiviral therapy.

PMID- 24576056
TI  - Functional divergence between the two P1-P2 stalk dimers on the ribosome in their
      interaction with ricin A chain.
AB  - The eukaryotic stalk, which is responsible for the recruitment of translation
      factors, is a pentamer containing two P1-P2 dimers with unclear modes of action.
      In Saccharomyces cerevisiae, P1/P2 proteins (individual P1 and P2 proteins) are
      organized into two distinct dimers, P1A-P2B and P1B-P2A. To investigate the
      functional contribution of each dimer on the ribosome, RTA (ricin A chain), which
      binds to the stalk to depurinate the SRL (sarcin/ricin loop), was used as a
      molecular probe in yeast mutants in which the binding site for one or the other
      dimer on P0 was deleted. Ribosome depurination and toxicity of RTA were greatly
      reduced in mutants containing only P1A-P2B on the ribosome, whereas those with
      only P1B-P2A were reduced less in depurination and were unaffected in toxicity.
      Ribosomes bearing P1B-P2A were depurinated by RTA at a similar level as wild
      type, but ribosomes bearing P1A-P2B were depurinated at a much lower level in
      vitro. The latter ribosomes showed the lowest association and almost no
      dissociation with RTA by surface plasmon resonance. These results indicate that
      the P1B-P2A dimer is more critical for facilitating the access of RTA to the SRL,
      providing the first in vivo evidence for functional divergence between the two
      stalk dimers on the ribosome. 

PMID- 24576058
TI  - Prediction of the key binding site of odorant-binding protein of Holotrichia
      oblita Faldermann (Coleoptera: Scarabaeida).
AB  - The scarab beetle Holotrichia oblita Faldermann (Coleoptera: Scarabaeidae) is a
      predominant underground pest in the northern parts of China, and its larvae
      (grubs) cause great economic losses because of its wide range of host plants and
      covert habitats. Environmentally friendly strategies for controlling adults would
      have novel and broad potential applications. One potential pest management
      measure is the regulation of olfactory chemoreception to control target insect
      pests. In the process of olfactory recognition, odorant-binding proteins (OBPs)
      are believed to carry hydrophobic odorants from the environment to the surface of
      olfactory receptor neurons. To obtain a better understanding of the relationship
      between OBP structures and their ligands, homology modelling and molecular
      docking have been conducted on the interaction between HoblOBP1 and hexyl
      benzoate in the present study. Based on the results, site-directed mutagenesis
      and binding experiments were combined to describe the binding sites of HoblOBP1
      and to explore its ligand-binding mechanism. After homology modelling of
      HoblOBP1, it was found that the three-dimensional structure of HoblOBP1 consists
      of six alpha-helices and three disulphide bridges that connect the helices, and
      the hydrophobic pockets are both composed of five helices. Based on the docking
      study, we found that van der Waals interactions and hydrophobic interactions are
      both important in the bonding between HoblOBP1 and hexyl benzoate. Intramolecular
      residues formed the hydrogen bonds in the C terminus of the protein and the bonds
      are crucial for the ligand-binding specificity. Finally, MET48, ILE80 and TYR111
      are binding sites predicted for HoblOBP1. Using site-directed mutagenesis and
      fluorescence assays, it was found that ligands could not be recognized by mutant
      of Tyr111. A possible explanation is that the compound could not be recognized by
      the mutant, and remains in the binding cavity because of the loss of the
      intramolecular hydrogen bonding that acts as a holder. So we believe that Tyr111
      of HoblOBP1 is a key binding site. We also believe that Ile80A is a very
      important binding site, especially to some ligands. 

PMID- 24576057
TI  - Negative symptoms and impaired social functioning predict later psychosis in
      Latino youth at clinical high risk in the North American prodromal longitudinal
      studies consortium.
AB  - AIM: Examining ethnically related variables in evaluating those at risk for
      psychosis is critical. This study investigated sociodemographic and clinical
      characteristics of Latino versus non-Latino clinical high-risk (CHR) subjects and
      healthy control (HC) subjects in the first North American Prodrome Longitudinal
      Study. METHODS: Fifty-six Latino CHR subjects were compared to 25 Latino HC and
      423 non-Latino CHR subjects across clinical and demographic variables. Thirty
      nine of the 56 CHR subjects completed at least one subsequent clinical evaluation
      over the 2.5-year period with 39% developing a psychotic illness. Characteristics
      of Latino CHR subjects who later converted to psychosis ('converters') were
      compared to those who did not ('non-converters'). RESULTS: Latino CHR subjects
      were younger than non-Latino CHR subjects and had less education than Latino HC
      subjects and non-Latino CHR counterparts. Latino CHR converters had higher scores
      than Latino non-converters on the Structured Interview for Prodromal Syndromes
      total negative symptoms that were accounted for by decreased expression of
      emotion and personal hygiene/social attentiveness subsections. Latino CHR
      converters scored lower on the global functioning:social scale, indicating worse
      social functioning than Latino non-converters. CONCLUSION: Based on this sample,
      Latino CHR subjects may seek treatment earlier and have less education than non
      Latino CHR subjects. Deficits in social functioning and impaired personal
      hygiene/social attentiveness among Latino CHR subjects predicted later psychosis
      and may represent important areas for future study. Larger sample sizes are
      needed to more thoroughly investigate the observed ethnic differences and risk
      factors for psychosis in Latino youth.

PMID- 24576059
TI  - Fenpropathrin biodegradation pathway in Bacillus sp. DG-02 and its potential for
      bioremediation of pyrethroid-contaminated soils.
AB  - The widely used insecticide fenpropathrin in agriculture has become a public
      concern because of its heavy environmental contamination and toxic effects on
      mammals, yet little is known about the kinetic and metabolic behaviors of this
      pesticide. This study reports the degradation kinetics and metabolic pathway of
      fenpropathrin in Bacillus sp. DG-02, previously isolated from the pyrethroid
      manufacturing wastewater treatment system. Up to 93.3% of 50 mg L(-1)
      fenpropathrin was degraded by Bacillus sp. DG-02 within 72 h, and the degradation
      rate parameters qmax, Ks, and Ki were determined to be 0.05 h(-1), 9.0 mg L(-1),
      and 694.8 mg L(-1), respectively. Analysis of the degradation products by gas
      chromatography-mass spectrometry led to identification of seven metabolites of
      fenpropathrin, which suggest that fenpropathrin could be degraded first by
      cleavage of its carboxylester linkage and diaryl bond, followed by degradation of
      the aromatic ring and subsequent metabolism. In addition to degradation of
      fenpropathrin, this strain was also found to be capable of degrading a wide range
      of synthetic pyrethroids including deltamethrin, lambda-cyhalothrin, beta
      cypermethrin, beta-cyfluthrin, bifenthrin, and permethrin, which are also widely
      used insecticides with environmental contamination problems with the degradation
      process following the first-order kinetic model. Bioaugmentation of fenpropathrin
      contaminated soils with strain DG-02 significantly enhanced the disappearance
      rate of fenpropathrin, and its half-life was sharply reduced in the soils. Taken
      together, these results depict the biodegradation mechanisms of fenpropathrin and
      also highlight the promising potentials of Bacillus sp. DG-02 in bioremediation
      of pyrethroid-contaminated soils. 

PMID- 24576060
TI  - The elusive effect of water and sanitation on the global burden of disease.

PMID- 24576061
TI  - Treatment of bipolar disorder in the Netherlands and concordance with treatment
      guidelines: study protocol of an observational, longitudinal study on
      naturalistic treatment of bipolar disorder in everyday clinical practice.
AB  - BACKGROUND: While various guidelines on the treatment of bipolar disorder have
      been published over the last decades, adherence to guidelines has been reported
      to be low. In this article we describe the protocol of a nationwide, multicenter,
      longitudinal, non-intervention study on the treatment of bipolar disorder in the
      Netherlands. Study aims are to provide information on the nature and content of
      outpatient treatment of bipolar disorder, to determine to what extent treatment
      is in concordance with the Dutch guideline for the treatment of bipolar disorder
      (2008), and to investigate the relationship of guideline concordance with
      symptomatic and functional outcome. METHODS/DESIGN: Between December 2009 and
      February 2010, all psychiatrists registered as member of the Dutch Psychiatric
      Association received a questionnaire with questions about their treatment
      setting, and whether they would be willing to participate in further research.
      Psychiatrists treating adult outpatients with bipolar disorder were invited to
      participate. Consenting psychiatrist subsequently approached all their patients
      with bipolar disorder. The study is performed with written patient and caregiver
      surveys at baseline and after 12 months, including data on demographics, illness
      characteristics, organization of care, treatments received, symptomatic and
      functional outcome, quality of life, and burden of care for informal caregivers.
      DISCUSSION: This study will provide information on the naturalistic treatment of
      bipolar disorder in the Netherlands, as well as degree of concordance of this
      treatment with the Dutch guideline, and its relationship with symptomatic and
      functional outcome. Limitations of a survey-based study are discussed.

PMID- 24576062
TI  - Southwest intrusion of 134Cs and 137Cs derived from the Fukushima Dai-ichi
      nuclear power plant accident in the Western North Pacific.
AB  - Enormous quantities of radionuclides were released into the ocean via both
      atmospheric deposition and direct release as a result of the Fukushima Dai-ichi
      Nuclear Power Plant (FNPP) accident. This study discusses the southward
      dispersion of FNPP-derived radioactive cesium (Cs) in subsurface waters. The
      southernmost point where we found the FNPP-derived (134)Cs (1.5-6.8 Bq m(-3)) was
      18  degrees N, 135  degrees E, in September 2012. The potential density at the
      subsurface peaks of (134)Cs (100-500 m) and the increased water column
      inventories of (137)Cs between 0 and 500 m after the winter of 2011-2012
      suggested that the main water mass containing FNPP-derived radioactive Cs was the
      North Pacific Subtropical Mode Water (NPSTMW), formed as a result of winter
      convection. We estimated the amount of (134)Cs in core waters of the western part
      of the NPSTMW to be 0.99 PBq (decay-corrected on 11 March 2011). This accounts
      for 9.0% of the (134)Cs released from the FNPP, with our estimation revealing
      that a considerable amount of FNPP-derived radioactive Cs has been transported to
      the subtropical region by the formation and circulation of the mode water.

PMID- 24576063
TI  - Marine biofouling resistance of polyurethane with biodegradation and
      hydrolyzation.
AB  - We have prepared polyurethane with poly(epsilon-caprolactone) (PCL) as the
      segments of the main chain and poly(triisopropylsilyl acrylate) (PTIPSA) as the
      side chains by a combination of radical polymerization and a condensation
      reaction. Quartz crystal microbalance with dissipation studies show that
      polyurethane can degrade in the presence of enzyme and the degradation rate
      decreases with the PTIPSA content. Our studies also demonstrate that polyurethane
      is able to hydrolyze in artificial seawater and the hydrolysis rate increases as
      the PTIPSA content increases. Moreover, hydrolysis leads to a hydrophilic surface
      that is favorable to reduction of the frictional drag under dynamic conditions.
      Marine field tests reveal that polyurethane has good antifouling ability because
      polyurethane with a biodegradable PCL main chain and hydrolyzable PTIPSA side
      chains can form a self-renewal surface. Polyurethane was also used to carry and
      release a relatively environmentally friendly antifoulant, and the combined
      system exhibits a much higher antifouling performance even in a static marine
      environment. 

PMID- 24576064
TI  - Knowledge, attitudes, and practices of parents in rural China on the use of
      antibiotics in children: a cross-sectional study.
AB  - BACKGROUND: The purpose of the study was to investigate parents' perceptions of
      antibiotic use for their children, interactions between parents and physicians
      regarding treatment with antibiotics, and factors associated with parents self
      medicating children with antibiotics. METHODS: A cross-sectional study was
      conducted in vaccination clinics in two rural Chinese counties. Primary
      caregivers (the child's parents in 97% of cases) visiting these clinics for the
      vaccination of their young children were given a 55-item structured questionnaire
      to collect information on the parents' knowledge and attitudes regarding when,
      why, and how to use antibiotics and on their practices of purchasing antibiotics
      and medicating children. RESULTS: Of the 854 participating primary caregivers,
      79% thought antibiotics could cure viral infections, and half believed that
      antibiotics could shorten the duration of upper respiratory tract infection.
      Parents reported a median of two hospital visits for their children during the
      previous 6 months, equal to the median number of antibiotic prescriptions
      received from physicians. Sixty-two percent of the parents had self-medicated
      their children with antibiotics. Living in rural villages (Adj OR = 1.643, 95%
      CI: 1.108-2.436), raising more than one child (Adj OR = 2.174, 95% CI: 1.485
      3.183), increasing age of child (Adj OR = 1.146, 95% CI: 1.037-1.266), purchasing
      antibiotics without a prescription (Adj OR = 6.264, 95% CI: 4.144-9.469), storing
      antibiotics at home (Adj OR = 2.792, 95% CI: 1.961-3.975) and good adherence to
      physicians' advice (Adj OR = 0.639, 95% CI: 0.451-0.906) were independently
      associated with self-medicating behavior. CONCLUSIONS: Low levels of knowledge on
      the use of antibiotics and a high prevalence of self-medicating children with
      antibiotics were observed among parents in rural China. Interventions for the
      rational use of antibiotics in children should focus on strengthening mass health
      education, improving effective communication between physicians and patients, and
      enforcing supervision of the sale of antibiotics in retail pharmacies.

PMID- 24576065
TI  - Over-expression of PRAS40 enhances insulin sensitivity in skeletal muscle.
AB  - CONTEXT: Silencing proline-rich Akt substrate of 40-kDa (PRAS40) impairs insulin
      signalling in skeletal muscle. OBJECTIVE: This study assessed the effects of over
      expressing wild type or mutant AAA-PRAS40, in which the major phosphorylation
      sites and mTORC1-binding site were mutated, on insulin signalling in skeletal
      muscle. RESULTS: Over-expression of WT-PRAS40, but not AAA-PRAS40, impaired the
      insulin-mediated activation of the mTORC1-pathway in human skeletal muscle cells
      (hSkMC). However, insulin-mediated Akt-phosphorylation was increased upon over
      expression of WT-PRAS40 both in hSkMC and mouse skeletal muscle. Also over
      expression of AAA-PRAS40 had an insulin-sensitizing effect, although to a lesser
      extent as WT-PRAS40. The insulin-sensitizing effect associated with increased
      IRS1 protein abundance and inhibition of proteasome activity. Finally, over
      expression of WT-PRAS40 reversed hyperinsulinemia-induced insulin resistance.
      CONCLUSION: This study identifies PRAS40 as a regulator of insulin sensitivity in
      hSkMC. In contrast to the mTORC1-pathway, the insulin-sensitizing action of
      PRAS40 occurs independent of binding of PRAS40 to the mTORC1-complex.

PMID- 24576066
TI  - Comparison of corneal safety and intraocular pressure-lowering effect of
      tafluprost ophthalmic solution with other prostaglandin ophthalmic solutions.
AB  - PURPOSE: The benzalkonium chloride (BAK) content of tafluprost ophthalmic
      solution (Tapros((r)): tafluprost) has been reduced to balance corneal safety and
      preservative effectiveness (old formulation: 0.01%; new formulation: 0.001%).
      However, no reports have been published on its clinical effect. Therefore, we
      conducted a clinical research study to compare the safety of BAK-reduced
      tafluprost on the ocular surface with other prostaglandin ophthalmic solutions.
      METHODS: This clinical study included 28 glaucoma patients (28 eyes) with a
      treatment history of latanoprost ophthalmic solution (Xalatan((r))) or travoprost
      ophthalmic solution (Travatan Z((r))), who presented with corneal epithelial
      disorders. The subjects were switched to BAK-reduced tafluprost, and its effect
      on the ocular surface was examined after 1 and 2 months of treatment [using
      fluorescein staining score, hyperemia, tear film breakup time, and intraocular
      pressure (IOP) lowering]. RESULTS: In all analyzed subjects (N=27), the
      fluorescein staining score was significantly improved after switching to BAK
      reduced tafluprost (P<0.0001). Conversely, the IOP-lowering effect was not
      notably changed. The subjects switched from latanoprost (n=10) showed significant
      improvement in fluorescein staining score (P<0.05) as well as in IOP lowering
      (P<0.01). The subjects switched from travoprost (n=17) also showed significant
      improvement in fluorescein staining score (P<0.001), but without a significant
      change in IOP lowering. CONCLUSIONS: Tafluprost with reduced BAK has potential as
      a superior antiglaucoma drug, not only for its IOP-lowering effect, but also for
      its good corneal safety profile.

PMID- 24576067
TI  - Children's racial bias in perceptions of others' pain.
AB  - Previous research indicates that American adults, both Black and White, assume a
      priori that Black people feel less pain than do White people (Trawalter, Hoffman,
      & Waytz, 2012, PLoS One, 7[11], 1-8). The present work investigates when in
      development this bias emerges. Five-, 7-, and 10-year-olds first rated the amount
      of pain they themselves would feel in 10 situations such as biting their tongue
      or hitting their head. They then rated the amount of pain they believed two other
      children - a Black child and a White child, matched to the child's gender - would
      feel in response to the same events. We found that by age 7, children show a weak
      racial bias and that by age 10, they show a strong and reliable racial bias.
      Consistent with research on adults, this bias was not moderated by race-related
      attitudes or interracial contact. This finding is important because knowing the
      age of emergence can inform the timing of interventions to prevent this bias. 

PMID- 24576069
TI  - Role of miR-21 and its signaling pathways in renal diseases.
AB  - miRNAs are endogenous non-coding RNAs that are ~22 nucleotides in length and can
      have structural, enzymatic and regulatory functions. miRNAs play important roles
      in the progression of renal fibrosis. miR-21, through a feed-forward loop and a
      downstream mediator of transforming growth factor-beta (TGF-beta), amplifies TGF
      beta signaling and promotes fibrosis. miR-21 is high on the list of non-coding,
      small, regulatory RNAs that promote renal fibrosis and emerges as a serum
      biomarker for kidney diseases, but many questions await answers. This review was
      performed to sum up the role of miR-21 and its signaling pathways in renal
      diseases.

PMID- 24576068
TI  - Intermittent preventive treatment of malaria with sulphadoxine-pyrimethamine
      during pregnancy in Burkina Faso: effect of adding a third dose to the standard
      two-dose regimen on low birth weight, anaemia and pregnancy outcomes.
AB  - BACKGROUND: Intermittent preventive treatment with sulphadoxine-pyrimethamine
      (IPTp-SP) is being implemented in most malaria endemic countries as a standard
      two-doses regimen as it reduces the risk of low birth weight (LBW) and the
      prevalence of maternal anaemia. Nevertheless, where the risk of infection close
      to delivery is high because of intense transmission, a third IPTp-SP dose may
      further reduce the negative effects of malaria on pregnancy outcome. METHODS:
      Pregnant women in the 2nd or 3rd trimester were randomized to receive either 2
      (SP2) or 3 doses (SP3) of SP. Trained field workers paid home visits to the women
      for drug administration according to a predefined drug delivery schedule. Women
      were encouraged to attend their scheduled ANC visits and to deliver at the health
      facilities where the new-born was weighed. The prevalence of LBW (<2500 g),
      severe anaemia (Hb < 8 g/dL) and premature birth was analysed using intention-to
      treat (ITT) and per-protocol (PP) analysis. RESULTS: Data from 1274 singleton
      pregnancies were analysed (641 in the SP3 and 633 in the SP2 group). The uptake
      of the intervention appeared to be low. Though the prevalence of LBW in both
      intervention groups was similar (adjusted Incident Rate Ratio, AIRR = 0.92,
      95%CI: 0.69-1.24) in the ITT analysis, the risk of severe anaemia was
      significantly lower in the SP3 group compared to the SP2 group (AIRR = 0.38,
      95%CI: 0.16 - 0.90). The PP analysis showed a trend of reduced risk of LBW,
      severe anaemia and premature delivery in the SP3 group, albeit the difference
      between two and three IPTp-SP did not reach statistical significance. CONCLUSION:
      The risk of LBW and severe anaemia tended to be lower in the SP3 group, though
      this was not statistically significant, probably due to the low uptake of the
      intervention which reduced the power of the study. Further studies are needed for
      establishing whether a third SP dose has a real benefit in preventing the
      negative effects of malaria in pregnancy in settings where transmission is
      markedly seasonal.

PMID- 24576070
TI  - Immediate and long-term outcomes of assault in pregnancy.
AB  - OBJECTIVE: We examined the immediate and long-term health outcomes of
      hospitalised pregnancy-related assault. METHODS: A retrospective review of
      hospital records was conducted using data from the New Zealand Ministry of
      Health's National Minimum Data Set of hospital discharges. The hospital records
      of pregnant women admitted to a public hospital in New Zealand between 2001 and
      2006 were included in this investigation. Unique identifiers were used to
      identify the index pregnancy event, subsequent discharge events and mortality for
      five years after the index event. Discharge records were grouped as follows:
      pregnancy-related hospital admission, but no associated or subsequent assault
      recorded (pregnant only); an assault-related hospital admission event after the
      pregnancy, but within five years of the index pregnancy (assault after
      pregnancy); an assault recorded within the same hospital admission event as the
      pregnancy (assault during pregnancy). Generalised linear models for the binomial
      family were conducted to explore increased risk ratios of adverse maternal, fetal
      and subsequent injury outcomes depending on group assignment. RESULTS: Compared
      with the pregnancy-only group, the assault after pregnancy and assault during
      pregnancy groups had increased risk ratios for death, preterm labour, antepartum
      haemorrhage, infectious complication, spontaneous abortion and stillbirth.
      CONCLUSION: Assault during pregnancy substantially increased the risks for a
      number of adverse maternal and fetal outcomes. The identification of women who
      live in a violent relationship and the provision of adequate social support to
      these women may reduce the risks of subsequent injury and adverse maternal and
      fetal outcomes.

PMID- 24576071
TI  - Effects of weighted sled towing on ground reaction force during the acceleration
      phase of sprint running.
AB  - Athletes use weighted sled towing to improve sprint ability, but little is known
      about its biomechanics. The purpose of this study was to investigate the effect
      of weighted sled towing with two different loads on ground reaction force. Ten
      physically active men (mean +/- SD: age 27.9 +/- 1.9 years; stature 1.76 +/- 0.06
      m; body mass 80.2 +/- 9.6 kg) performed 5 m sprints under three conditions; (a)
      unresisted, (b) towing a sled weighing 10% of body mass (10% condition) and (c)
      towing a sled weighing 30% of body mass (30% condition). Ground reaction force
      data during the second ground contact after the start were recorded and compared
      across the three conditions. No significant differences between the unresisted
      and 10% conditions were evident, whereas the 30% condition resulted in
      significantly greater values for the net horizontal and propulsive impulses (P <
      0.05) compared with the unresisted condition due to longer contact time and more
      horizontal direction of force application to the ground. It is concluded that
      towing a sled weighing 30% of body mass requires more horizontal force
      application and increases the demand for horizontal impulse production. In
      contrast, the use of 10% body mass has minimal impact on ground reaction force.

PMID- 24576073
TI  - Yttrium hydride nanoantennas for active plasmonics.
AB  - A key challenge for the development of active plasmonic nanodevices is the lack
      of materials with fully controllable plasmonic properties. In this work, we
      demonstrate that a plasmonic resonance in top-down nanofabricated yttrium
      antennas can be completely and reversibly turned on and off using hydrogen
      exposure. We fabricate arrays of yttrium nanorods and optically observe, in
      extinction spectra, the hydrogen-induced phase transition between the metallic
      yttrium dihydride and the insulating trihydride. Whereas the yttrium dihydride
      nanostructures exhibit a pronounced particle plasmon resonance, the transition to
      yttrium trihydride leads to a complete vanishing of the resonant behavior. The
      plasmonic resonance in the dihydride state can be tuned over a wide wavelength
      range by simply varying the size of the nanostructures. Furthermore, we develop
      an analytical diffusion model to explain the temporal behavior of the hydrogen
      loading and unloading trajectories observed in our experiments and gain
      information about the thermodynamics of our device. Thus, our nanorod system
      serves as a versatile basic building block for active plasmonic devices ranging
      from switchable perfect absorbers to active local heating control elements. 

PMID- 24576072
TI  - miR-181a mediates TGF-beta-induced hepatocyte EMT and is dysregulated in
      cirrhosis and hepatocellular cancer.
AB  - BACKGROUND & AIMS: Epithelial-mesenchymal transition (EMT) has been implicated in
      the processes of embryogenesis, tissue fibrosis and carcinogenesis. Transforming
      growth factor-beta (TGF-beta) has been identified as a key driver of EMT and
      plays a key role in the pathogenesis of cirrhosis and hepatocellular carcinoma
      (HCC). The aim was to identify microRNA (miR) expression in TGF-beta-induced
      hepatocyte EMT. METHODS: We treated a human hepatocyte cell line PH5CH8 with TGF
      beta to induce an EMT-like change in phenotype and then identified dysregulated
      miRs using TaqMan Low Density Arrays. MiR expression was altered using miR-181a
      mimic and inhibitor in the same system and gene changes were identified using
      TaqMan gene arrays. MiR-181a gene expression was measured in human and mouse
      cirrhotic or HCC liver tissue samples. Gene changes were identified in rAAV-miR
      181a-expressing mouse livers using TaqMan gene arrays. RESULTS: We identified miR
      181a as a miR that was significantly up-regulated in response to TGF-beta
      treatment. Over-expression of a miR-181a mimic induced an in vitro EMT-like
      change with a phenotype similar to that seen with TGF-beta treatment alone and
      was reversed using a miR-181a inhibitor. MiR-181a was shown to be up-regulated in
      experimental and human cirrhotic and HCC tissue. Mouse livers expressing rAAV-miR
      181a showed genetic changes associated with TGF-beta signalling and EMT.
      CONCLUSIONS: MiR-181a had a direct effect in inducing hepatocyte EMT and was able
      to replace TGF-beta-induced effects in vitro. MiR-181a was over-expressed in
      cirrhosis and HCC and is likely to play a role in disease pathogenesis.

PMID- 24576075
TI  - Death due to coronary artery insufficiency following blunt trauma to the chest.
AB  - There have been numerous reports of sudden cardiac death following blunt trauma
      to the chest, but there is lack of such references in forensic literature. It is
      the court of law which makes decision about trauma precipitating natural events.
      The forensic pathologist is scientifically trained in the medical field and would
      be in a better position to give clear picture about the victim's general status
      at the time of death, exact nature and severity of the illness he is suffering
      from if any. He can also assess the nature and severity of injuries sustained,
      and thus, his opinion as to the possible role played by the traumatic event in
      bringing about the death is valuable. This paper will discuss the mechanism of
      cardiac injury or possible cardiac injury and sudden death of an apparently
      healthy 36-year-old male following blunt chest trauma sustained during alleged
      assault by his neighbor. 

PMID- 24576074
TI  - A new construction technique for tissue-engineered heart valves using the self
      assembly method.
AB  - Tissue engineering appears as a promising option to create new heart valve
      substitutes able to overcome the serious drawbacks encountered with mechanical
      substitutes or tissue valves. The objective of this article is to present the
      construction method of a new entirely biological stentless aortic valve using the
      self-assembly method and also a first assessment of its behavior in a bioreactor
      when exposed to a pulsatile flow. A thick tissue was created by stacking several
      fibroblast sheets produced with the self-assembly technique. Different sets of
      custom-made templates were designed to confer to the thick tissue a three
      dimensional (3D) shape similar to that of a native aortic valve. The construction
      of the valve was divided in two sequential steps. The first step was the
      installation of the thick tissue in a flat preshaping template followed by a 4
      week maturation period. The second step was the actual cylindrical 3D forming of
      the valve. The microscopic tissue structure was assessed using histological cross
      sections stained with Masson's Trichrome and Picrosirius Red. The thick tissue
      remained uniformly populated with cells throughout the construction steps and the
      dense extracellular matrix presented corrugated fibers of collagen. This first
      prototype of tissue-engineered heart valve was installed in a bioreactor to
      assess its capacity to sustain a light pulsatile flow at a frequency of 0.5 Hz.
      Under the light pulsed flow, it was observed that the leaflets opened and closed
      according to the flow variations. This study demonstrates that the self-assembly
      method is a viable option for the construction of complex 3D shapes, such as
      heart valves, with an entirely biological material.

PMID- 24576076
TI  - The antenna-specific odorant-binding protein AlinOBP13 of the alfalfa plant bug
      Adelphocoris lineolatus is expressed specifically in basiconic sensilla and has
      high binding affinity to terpenoids.
AB  - Odorant-binding proteins (OBPs) are crucial in the olfactory pathway of insects.
      In the present study, the antenna-enriched OBP AlinOBP13 was investigated because
      of its potential contribution to the peripheral olfactory perception in the
      alfalfa plant bug Adelphocoris lineolatus. The results of quantitative reverse
      transcriptase-PCR showed that the transcript level of AlinOBP13 was higher in the
      adult stage than in the nymph stages. The transcript levels of AlinOBP13 in the
      male and female antennae significantly increased after 4 and 8 h of starvation,
      respectively. Fine ultrastructures of different types of chemosensilla in both
      female and male antennae were investigated using transmission electron microscopy
      and immunocytochemical labelling. The results revealed that the anti-AlinOBP13
      antiserum strongly and specifically labelled short basiconic sensilla; this
      antiserum was restricted to the inner lumen and the cavities below the sensillum
      base of the sensilla. By contrast, multiporous sensilla trichodea, medium long
      sensilla basiconica, and aporous sensilla chaetica were not labelled. The present
      study is the first to report an OBP showing specific expression in the short
      basiconic sensilla of a member of the Hemipteran species. The results of a
      fluorescence displacement binding assay indicated that recombinant AlinOBP13
      showed a more specific binding preference to terpenoids than to sex pheromones
      and other classes of chemicals. This binding ability was dramatically affected by
      pH; higher binding affinities were displayed at pH 10.0 than at pH 7.4 and 5.0.
      In addition, the results of dose-dependent electroantennogram recordings from the
      antennae showed that both female and male adult bugs responded to the terpenoids
      tested, suggesting an apparent physiological relevance of AlinOBP13 in A.
      lineolatus chemoreception. The results of this study suggest that AlinOBP13
      functions as a specific carrier of terpenoids and provide insights into the
      mechanism of A. lineolatus in response to green volatiles. 

PMID- 24576077
TI  - Psychotherapy for adolescents and young adults at high risk for psychosis: a
      systematic review.
AB  - AIM: Unlike medication treatment, which may confer an unfavourable risk-benefit
      ratio, psychosocial intervention has been an emerging target of recent randomized
      controlled trials (RCTs) assessing its efficacy in delaying or preventing the
      onset of psychosis in individuals identified at 'clinical high risk'. Literature
      comparing qualitative differences in these psychotherapeutic interventions is
      scarce. The aim of the current study was to conduct a PRISMA systematic review
      evaluating the efficacy of psychotherapeutic interventions in reducing the rates
      of conversion to psychosis in clinical high-risk individuals. METHODS: RCTs were
      identified in PubMed, Medline and PsycINFO databases up to 30 November 2013. Six
      studies (comprising 800 participants) met review inclusion criteria. Three
      investigators performed data extraction independently by using a pre-structured
      selection form, and conducted risk of bias assessment employing the Cochrane
      approach. RESULTS: All six studies employed cognitive behaviour therapy as a core
      element. Three trials achieved a significant effect. The two trials that employed
      cognitive behaviour therapy enhanced for the specialized needs of clinical high
      risk patients maintained significant effects at post-treatment follow up.
      CONCLUSION: Evidence from recent trials suggest that cognitive behaviour therapy
      may be beneficial in delaying or preventing onset of psychosis in clinical high
      risk individuals, although effect sizes to date appear small. Further research is
      needed in larger samples to establish whether cognitive behaviour therapy is
      efficacious, and if additional intervention components can enhance established
      psychotherapies.

PMID- 24576078
TI  - Reactivity for the Diels-Alder reaction of cumulenes: a distortion-interaction
      analysis along the reaction pathway.
AB  - Cumulenes, including allene, ketenimine, and ketene, can be employed as
      dienophiles in Diels-Alder type reactions. The activation energies of a Diels
      Alder reaction between cyclopentadiene and either the C ? C bond or the other C ?
      X (X = C, N, or O) bond in cumulenes have been calculated by G3B3, CBS-QB3, M06
      2X, and B3LYP methods. The reactivity trend for the C ? C bond in cumulenes is
      allene > ketenimine > ketene and that of the C ? X bond in cumulenes is ketene >
      allene > ketenimine. Application of distortion-interaction analysis only at
      transition states does not give a satisfactory explanation for these
      reactivities. By employing distortion-interaction analysis along reaction
      pathways, we found that the reactivity of the C ? C and C ? X bond in cumulenes
      is controlled by both of its distortion and interaction energies. The lowest
      distortion energy of allene leads to its highest reactivity; the higher
      interaction energy results in higher activation energy of ketene than that of
      ketenimine. Compared with the reactivity of the C ? X bond in cumulenes, the C ?
      O bond in ketene has the lowest activation energy to react with cyclopentadiene,
      due to its lowest interaction energy, whereas the lower distortion energy of
      ketenimine than that of allene leads to a higher reactivity. The distortion
      energy of the reactants can be attributed to folding ability and molecule strain.
      The corresponding interaction energy of the reactants is controlled by orbital
      interaction, closed-shell repulsion, and static repulsion.

PMID- 24576080
TI  - Metal transport in the boreal landscape-the role of wetlands and the affinity for
      organic matter.
AB  - Stream water concentrations of 13 major and trace elements (Al, Ba, Ca, Cr, Cu,
      La, Mg, Na, Ni, Si, Sr, U, Y) were used to estimate fluxes from 15 boreal
      catchments. All elements displayed a significant negative correlation to the
      wetland coverage, but the influence of wetlands was stronger for organophilic
      metals; 73% of the spatial differences in the normalized element fluxes could be
      explained based only on the wetland coverage and the affinity for organic matter,
      which was quantified using thermodynamic modeling. When the analysis was
      restrained to the smaller streams (<10 km(2)) the explanatory power increased to
      88%. The results suggest that wetlands may decrease the fluxes of metals from
      boreal forests to downstream recipients by up to 40% at otherwise similar runoff.
      We suggest that the decrease in element fluxes is caused by a combination of low
      weathering in peat soils and accumulation of organophilic metals in peat. The
      model could not explain the spatial patterns for some metals with low affinity
      for organic matter, some redox-sensitive metals, and some metals with
      exceptionally high atmospheric deposition, but the results still demonstrate that
      wetlands play an important role for the biogeochemical cycling of many metals in
      the boreal landscape. 

PMID- 24576079
TI  - Effects of classroom bilingualism on task-shifting, verbal memory, and word
      learning in children.
AB  - We examined the effects of classroom bilingual experience in children on an array
      of cognitive skills. Monolingual English-speaking children were compared with
      children who spoke English as the native language and who had been exposed to
      Spanish in the context of dual-immersion schooling for an average of 2 years. The
      groups were compared on a measure of non-linguistic task-shifting; measures of
      verbal short-term and working memory; and measures of word learning. The two
      groups of children did not differ on measures of non-linguistic task-shifting and
      verbal short-term memory. However, the classroom-exposure bilingual group
      outperformed the monolingual group on the measure of verbal working memory and a
      measure of word learning. Together, these findings indicate that while exposure
      to a second language in a classroom setting may not be sufficient to engender
      changes in cognitive control, it can facilitate verbal memory and verbal
      learning.

PMID- 24576082
TI  - Risk factors for early hospital readmission in low-income elderly adults.
AB  - OBJECTIVES: To identify risk factors for early hospital readmission in low-income
      community-dwelling older adults. DESIGN: Prospective cohort study. SETTING:
      University-affiliated urban safety-net healthcare system in Indianapolis,
      Indiana. PARTICIPANTS: Community-dwelling adults aged 65 and older with annual
      income less than 200% of the federal poverty level and enrolled in the Geriatric
      Resources for Assessment and Care of Elders (GRACE) randomized controlled trial
      (N = 951). MEASUREMENTS: Participant health and functional status at baseline and
      6, 12, 18, and 24 months. Early readmission was defined as a repeat
      hospitalization occurring within 30 days of a prior hospital discharge. Candidate
      risk factors included sociodemographic characteristics, health and functional
      status, prior care, lifestyle, and satisfaction with care. RESULTS: Of 457 index
      admissions in 328 participants, 85 (19%) were followed by an early readmission.
      The independent risk factors for early readmission identified according to
      regression analysis were living alone (odds ratio (OR) = 1.71, 95% confidence
      interval (CI) = 1.02-2.87), fair or poor satisfaction with primary care physician
      (OR = 2.12, 95% CI = 1.01-4.46), not having Medicaid (OR = 1.80, 95% CI = 1.05
      3.11), receiving a new assistive device in the past 6 months (OR = 2.26, 95% CI =
      1.26-4.05), and staying in a nursing home in the past 6 months (OR = 5.08, 95% CI
      = 1.56-16.53). Age, race, sex, education, and chronic diseases were not
      associated with early readmission. CONCLUSION: A broad range of nonmedical risk
      factors played a greater role than previously recognized in early hospital
      readmission of low-income seniors.

PMID- 24576081
TI  - Heart smart for women: a community-based lifestyle change intervention to reduce
      cardiovascular risk in rural women.
AB  - PURPOSE: Cardiovascular disease (CVD) is the leading cause of death for rural
      women in the United States. Lifestyle change interventions in group settings
      focused on increasing physical activity and improving nutrition have been shown
      to help reduce the risk for CVD. This paper describes the implementation and
      evaluation of Heart Smart for Women (HSFW), a 12-week lifestyle behavior change
      intervention to reduce CVD risk for women in the rural southernmost 7 counties
      (S7) of Illinois. METHODS: The HSFW evidence-based lifestyle intervention was
      delivered by a trained facilitator in 12 weekly 1-hour sessions to groups of
      women in the rural S7 region of Illinois. Dietary and physical activity
      assessments were collected at baseline, postintervention, and 1 year. Clinical
      measurements were taken at baseline, 6 months and 1 year. Data were analyzed for
      change in behavioral and clinical outcomes over time. FINDINGS: In total, 162
      women completed HSFW in 13 communities across the S7 region. HSFW participants
      showed improvement in dietary and physical activity indicators at the end of the
      12-week intervention, but only increases in vegetable consumption and physical
      activity were sustained over 1 year. A decrease in total cholesterol was observed
      at 6 months but not maintained at 1 year. CONCLUSIONS: HSFW led to short-term,
      moderate changes in nutrition and physical activity in rural women, but some
      health improvements were not sustained at 1 year. These findings suggest that
      more intensive follow-up maybe required to help maintain long-term behavior
      change, especially in rural areas where women are geographically dispersed.

PMID- 24576083
TI  - Enhanced surveillance of acute flaccid paralysis following importation of wild
      poliovirus in Xinjiang Uygur Autonomous Region, China.
AB  - BACKGROUND: After being polio free for more than 10 years, an outbreak occurred
      in China in 2011 in Xinjiang Uygur Autonomous Region (Xinjiang) following the
      importation of wild poliovirus (WPV) originating from neighboring Pakistan.
      METHODS: To strengthen acute flaccid paralysis (AFP) surveillance in Xinjiang,
      "zero case daily reporting" and retrospective searching of AFP cases were
      initiated after the confirmation of the WPV outbreak. To pinpoint all the polio
      cases in time, AFP surveillance system was expanded to include persons of all
      ages in the entire population in Xinjiang. RESULTS: Totally, 578 AFP cases were
      reported in 2011 in Xinjiang, including 21 WPV cases, 23 clinical compatible
      polio cases and 534 non-polio AFP cases. Of the 44 polio cases, 27 (61.4%) cases
      were reported among adults aged 15-53 years. Strengthening AFP surveillance
      resulted in an increase in the number of non-polio AFP cases in 2011 (148
      children < 15 years) compared with 76 cases < 15 years in 2010. The AFP
      surveillance system in Xinjiang was sensitive enough to detect polio cases, with
      the AFP incidence of 3.28/100,000 among children < 15 years of age. CONCLUSIONS:
      Incorporating adult cases into the AFP surveillance system is of potential value
      to understand the overall characteristics of the epidemic and to guide emergency
      responses, especially in countries facing WPV outbreak following long-term polio
      free status. The AFP surveillance system in Xinjiang was satisfactory despite
      limitations in biological sample collection.

PMID- 24576084
TI  - Patient safety incidents in home hospice care: the experiences of hospice
      interdisciplinary team members.
AB  - BACKGROUND: Hospice provides a full range of services for patients near the end
      of life, often in the patient's own home. There are no published studies that
      describe patient safety incidents in home hospice care. OBJECTIVE: The study
      objective was to explore the types and characteristics of patient safety
      incidents in home hospice care from the experiences of hospice interdisciplinary
      team members. METHODS: The study design is qualitative and descriptive. From a
      convenience sample of 17 hospices in 13 states we identified 62 participants
      including hospice nurses, physicians, social workers, chaplains, and home health
      aides. We interviewed a separate sample of 19 experienced hospice leaders to
      assess the credibility of primary results. Semistructured telephone interviews
      were recorded and transcribed. Four researchers used an editing technique to
      identify common themes from the interviews. RESULTS: Major themes suggested a
      definition of patient safety in home hospice that includes concern for
      unnecessary harm to family caregivers or unnecessary disruption of the natural
      dying process. The most commonly described categories of patient harm were
      injuries from falls and inadequate control of symptoms. The most commonly cited
      contributing factors were related to patients, family caregivers, or the home
      setting. Few participants recalled incidents or harm related to medical errors by
      hospice team members. CONCLUSIONS: This is the first study to describe patient
      safety incidents from the experiences of hospice interdisciplinary team members.
      Compared with patient safety studies from other health care settings,
      participants recalled few incidents related to errors in evaluation, treatment,
      or communication by the hospice team.

PMID- 24576086
TI  - Diversity and activity of sulphur-oxidizing bacteria and sulphate-reducing
      bacteria in landfill cover soils.
AB  - Sulphur bioconversion in landfill cover soils, including the metabolism of
      sulphur-oxidizing bacteria (SOB) and sulphate-reducing bacteria (SRB), is one of
      the important processes affecting H2 S emission from landfills. In this study,
      two landfills with or without landfill gas collection and utilization system were
      investigated to characterize the role of biotic and abiotic factors affecting
      diversity and activity of SOB and SRB in the landfill cover soils. The results
      revealed that the potential sulphur oxidation rates (SORs) and sulphate reduction
      rates (SRRs) varied with landfill sites and depths. SOR was significantly
      correlated with pH and SO4 (2-) , while SRR was significantly related with pH.
      The populations of both SOB and SRB were low in the acidic landfill cover soils
      (pH = 4.7-5.37). Cloning and terminal restriction fragment length polymorphism
      profiles of soxB and dsrB showed that SOB including Halothiobacillus,
      Thiobacillus, Thiovirga and Bradyrhizobium, and SRB including Desulfobacca,
      Desulforhabdus and Syntrophobacter dominated in the landfill cover soils, and
      their distributions were affected mainly by pH value and organic matter contents
      of soils. SIGNIFICANCE AND IMPACT OF THE STUDY: High diversity of sulphur
      oxidizing bacteria (SOB) and sulphate-reducing bacteria (SRB) presented in the
      landfill cover soils. Among the physicochemical properties of soils (moisture
      content, pH, organic materials, SO4 (2-) , acid volatile sulphide and total
      sulphur), pH was the most important factor affecting the diversity and activity
      of SOB and SRB in the landfill cover soils. Higher pH of landfill cover soils
      (i.e. neutral or slight alkaline) was favourable for the growth of SOB and SRB,
      leading to a rapid bioconversion of sulphur. These findings are helpful to
      optimize sulphur biotransformation in landfill cover soils and to control odour
      pollution at landfills.

PMID- 24576087
TI  - Vitamin D concentrations in pregnant women with diabetes attending for antenatal
      care in Far North Queensland.
AB  - Serum concentrations of vitamin D were measured in 101 pregnant women with
      diabetes, both pre-existing and gestational, who attended for antenatal care in
      Cairns Base Hospital. Eighty-two (81.2%) had sufficient concentrations of vitamin
      D, 12 (11.9%) had levels indicating insufficiency and 7 (6.9%) were deficient.
      These findings contrast with those in the general population of pregnant women in
      the region, among whom 93.1% have been shown to have sufficient levels. The study
      contributes to the ongoing debate around the need for universal antenatal vitamin
      D screening in Australia. 

PMID- 24576085
TI  - Inhibition of histone binding by supramolecular hosts.
AB  - The tandem PHD (plant homeodomain) fingers of the CHD4 (chromodomain helicase DNA
      binding protein 4) ATPase are epigenetic readers that bind either unmodified
      histone H3 tails or H3K9me3 (histone H3 trimethylated at Lys9). This dual
      function is necessary for the transcriptional and chromatin remodelling
      activities of the NuRD (nucleosome remodelling and deacetylase) complex. In the
      present paper, we show that calixarene-based supramolecular hosts disrupt binding
      of the CHD4 PHD2 finger to H3K9me3, but do not affect the interaction of this
      protein with the H3K9me0 (unmodified histone H3) tail. A similar inhibitory
      effect, observed for the association of chromodomain of HP1gamma (heterochromatin
      protein 1gamma) with H3K9me3, points to a general mechanism of methyl-lysine
      caging by calixarenes and suggests a high potential for these compounds in
      biochemical applications. Immunofluorescence analysis reveals that the
      supramolecular agents induce changes in chromatin organization that are
      consistent with their binding to and disruption of H3K9me3 sites in living cells.
      The results of the present study suggest that the aromatic macrocyclic hosts can
      be used as a powerful new tool for characterizing methylation-driven epigenetic
      mechanisms.

PMID- 24576088
TI  - Zirconia-Based Screw-Retained Prostheses Supported by Implants: A Retrospective
      Study on Technical Complications and Failures.
AB  - BACKGROUND: Little information is yet available on zirconia-based prostheses
      supported by implants. PURPOSE: To evaluate technical problems and failures of
      implant-supported zirconia-based prostheses with exclusive screw-retention.
      MATERIAL AND METHODS: Consecutive patients received screw-retained zirconia-based
      prostheses supported by implants and were followed over a time period of 5 years.
      The implant placement and prosthetic rehabilitation were performed in one
      clinical setting, and all patients participated in the maintenance program. The
      treatment comprised single crowns (SCs) and fixed dental prostheses (FDPs) of
      three to 12 units. Screw-retention of the CAD/CAM-fabricated SCs and FDPs was
      performed with direct connection at the implant level. The primary outcome was
      the complete failure of zirconia-based prostheses; outcome measures were fracture
      of the framework or extensive chipping resulting in the need for refabrication. A
      life table analysis was performed, the cumulative survival rate (CSR) calculated,
      and a Kaplan-Meier curve drawn. RESULTS: Two hundred and ninety-four implants
      supported 156 zirconia-based prostheses in 95 patients (52 men, 43 women, average
      age 59.1 +/- 11.7 years). Sixty-five SCs and 91 FDPs were identified, comprising
      a total of 441 units. Fractures of the zirconia framework and extensive chipping
      resulted in refabrication of nine prostheses. Nearly all the prostheses (94.2%)
      remained in situ during the observation period. The 5-year CSR was 90.5%, and 41
      prostheses (14 SCs, 27 FDPs) comprising 113 units survived for an observation
      time of more than 5 years. Six SCs exhibited screw loosening, and polishing of
      minor chipping was required for five prostheses. CONCLUSIONS: This study shows
      that zirconia-based implant-supported fixed prostheses exhibit satisfactory
      treatment outcomes and that screw-retention directly at the implant level is
      feasible.

PMID- 24576090
TI  - Aging of running shoes and its effect on mechanical and biomechanical variables:
      implications for runners.
AB  - This study investigates the effect of running shoes' aging on mechanical and
      biomechanical parameters as a function of midsole materials (viscous,
      intermediate, elastic) and ground inclination. To this aim, heel area of the shoe
      (under calcaneal tuberosity) was first mechanically aged at realistic frequency
      and impact magnitudes based on a 660 km training plan. Stiffness (ST) and
      viscosity were then measured on both aged and matching new shoes, and
      repercussions on biomechanical variables (joint kinematics, muscular pre
      activation, vertical ground reaction force and tibial acceleration) were assessed
      during a leg-extended stepping-down task designed to mimic the characteristics of
      running impacts. Shoes' aging led to increased ST (means: from 127 to 154 N ? mm(
      1)) and decreased energy dissipation (viscosity) (means: from 2.19 to 1.88 J).
      The effects induced by mechanical changes on body kinematics were very small.
      However, they led with the elastic shoe to increased vastus lateralis pre
      activation, tibial acceleration peak (means: from 4.5 g to 5.2 g) and rate. Among
      the three shoes tested, the shoe with intermediate midsole foam provided the best
      compromise between viscosity and elasticity. The optimum balance remains to be
      found for the design of shoes regarding at once cushioning, durability and injury
      prevention.

PMID- 24576089
TI  - Strength of axial water ligation in substrate-free cytochrome P450s is isoform
      dependent.
AB  - The heme-containing cytochrome P450s exhibit isoform-dependent ferric spin
      equilibria in the resting state and differential substrate-dependent spin
      equilibria. The basis for these differences is not well understood. Here,
      magnetic circular dichroism (MCD) reveals significant differences in the resting
      low spin ligand field of CYPs 3A4, 2E1, 2C9, 125A1, and 51B1, which indicates
      differences in the strength of axial water ligation to the heme. The near
      infrared bands that specifically correspond to charge-transfer porphyrin-to-metal
      transitions span a range of energies of nearly 2 kcal/mol. In addition, the
      experimentally determined MCD bands are not entirely in agreement with the
      expected MCD energies calculated from electron paramagnetic resonance parameters,
      thus emphasizing the need for the experimental data. MCD marker bands of the high
      spin heme between 500 and 680 nm were also measured and suggest only a narrow
      range of energies for this ensemble of high spin Cys(S(-)) -> Fe(3+) transitions
      among these isoforms. The differences in axial ligand energies between CYP
      isoforms of the low spin states likely contribute to the energetics of substrate
      dependent spin state perturbation. However, these ligand field energies do not
      correlate with the fraction of high spin vs low spin in the resting state enzyme,
      suggestive of differences in water access to the heme or isoform-dependent
      differences in the substrate-free high spin states as well. 

PMID- 24576091
TI  - Detecting 'infant-directedness' in face and voice.
AB  - Five- and 3-month-old infants' perception of infant-directed (ID) faces and the
      role of speech in perceiving faces were examined. Infants' eye movements were
      recorded as they viewed a series of two side-by-side talking faces, one infant
      directed and one adult-directed (AD), while listening to ID speech, AD speech, or
      in silence. Infants showed consistently greater dwell time on ID faces vs. AD
      faces, and this ID face preference was consistent across all three sound
      conditions. ID speech resulted in higher looking overall, but it did not increase
      looking at the ID face per se. Together, these findings demonstrate that infants'
      preferences for ID speech extend to ID faces.

PMID- 24576092
TI  - Flow pattern analysis in a highly stenotic patient-specific carotid bifurcation
      model using a turbulence model.
AB  - The aim of this study is to investigate the blood flow pattern in carotid
      bifurcation with a high degree of luminal stenosis, combining in vivo magnetic
      resonance imaging (MRI) and computational fluid dynamics (CFD). A newly developed
      two-equation transitional model was employed to evaluate wall shear stress (WSS)
      distribution and pressure drop across the stenosis, which are closely related to
      plaque vulnerability. A patient with an 80% left carotid stenosis was imaged
      using high resolution MRI, from which a patient-specific geometry was
      reconstructed and flow boundary conditions were acquired for CFD simulation. A
      transitional model was implemented to investigate the flow velocity and WSS
      distribution in the patient-specific model. The peak time-averaged WSS value of
      approximately 73 Pa was predicted by the transitional flow model, and the regions
      of high WSS occurred at the throat of the stenosis. High oscillatory shear index
      values up to 0.50 were present in a helical flow pattern from the outer wall of
      the internal carotid artery immediately after the throat. This study shows the
      potential suitability of a transitional turbulent flow model in capturing the
      flow phenomena in severely stenosed carotid arteries using patient-specific MRI
      data and provides the basis for further investigation of the links between
      haemodynamic variables and plaque vulnerability. It may be useful in the future
      for risk assessment of patients with carotid disease.

PMID- 24576095
TI  - TIGAR's promiscuity.
AB  - TIGAR [TP53 (tumour protein 53)-induced glycolysis and apoptosis regulator]
      protein is known for its ability to inhibit glycolysis, shifting glucose
      consumption towards the pentose phosphate pathway to promote antioxidant
      protection of cancer cells. According to sequence homology and activity analyses,
      TIGAR was initially considered to be a fructose-2,6-bisphosphatase; it has thus
      received much attention in cancer cell metabolism, given its dependence on p53
      and the key role of F26BP (fructose 2,6-bisphosphate) at modulating glycolysis
      and gluconeogenesis. However, in a rigorous study published in this issue of the
      Biochemical Journal, Gerin and colleagues report that recombinant TIGAR is a
      23BPG (2,3-bisphosphoglycerate) phosphatase, although it also dephosphorylates
      other carboxylic acid-phosphate esters and, weakly, F26BP. As such, inhibition of
      endogenous TIGAR leads to a dramatic increase in cellular 23BPG, influencing
      F26BP to a lower extent that depends on the cellular context. These results
      challenge the currently held notion that TIGAR modulates glycolysis through
      decreasing F26BP, and opens a yet unrecognized function(s) for TIGAR-mediated
      23BPG control of cellular metabolism in health and disease. 

PMID- 24576096
TI  - Antinociceptive and selected physiological effects of morphine and xylazine on
      tiletamine-zolazepam anesthesia in llamas.
AB  - OBJECTIVE: Evaluate antinociception, anesthesia, and recovery in llamas given
      tiletamine-zolazepam (TZ) with either morphine, xylazine, morphine and xylazine,
      or saline. STUDY DESIGN: Randomized crossover experimental study. ANIMALS: Six
      healthy, adult intact male llamas. METHODS: Llamas were given each of four
      treatments intramuscularly with a 1-week washout: TZ (2 mg kg(-1) ) combined with
      either morphine (0.5 mg kg(-1) ; M), xylazine (0.15 mg kg(-1) ; X), morphine (0.5
      mg kg(-1) ) and xylazine (0.15mg kg(-1) ) (MX), or saline (C). Llamas breathed
      room air during the experiment. Characteristics of anesthesia, recovery, and
      selected cardiopulmonary variables were recorded. Antinociception was assessed by
      clamping a claw at 5-minute intervals. Data were analyzed using a mixed-model
      anova and Tukey-Kramer test, and are expressed as least squares mean +/- SEM.
      Significance was set at p < 0.05. RESULTS: No llama in the control group
      demonstrated antinociception. Antinociception was longest with treatment MX,
      followed by treatments X and M, respectively. Heart rates in llamas given
      treatments X and MX were significantly lower than with other treatments. The
      respiratory rate in llamas given treatment C was greater (p < 0.05) than for all
      other treatments, however, the respiratory rate was not significantly different
      among treatments X, M and MX. The PaO2 for llamas given MX remained <60 mmHg
      throughout the 20 minute period of blood gas analysis. Mean arterial blood
      pressure in llamas in treatment MX was less than for treatments M or C.
      CONCLUSION AND CLINICAL RELEVANCE: The combination of morphine (0.5 mg kg(-1) )
      and xylazine (0.15 mg kg(-1) ) increased the duration of antinociception compared
      with xylazine alone, in TZ-anesthetized llamas. Treatments X, M and MX were
      associated with hypoxemia (PaO2 < 60 mmHg).

PMID- 24576097
TI  - Sex differences in the construct overlap of frailty and depression: evidence from
      the Health and Retirement Study.
AB  - OBJECTIVES: To determine the degree of diagnostic overlap between frailty and
      depression and to investigate whether sex differences in symptom endorsement
      influence this overlap. DESIGN: Cross-sectional latent class analysis. SETTING:
      Data were from the 2008 wave of the Health and Retirement Study, a nationally
      representative longitudinal survey of health characteristics of older adults.
      PARTICIPANTS: Community-dwelling adults aged 65 and older completing a general
      health questionnaire and consenting to physical measurements (N = 3,665).
      MEASUREMENTS: Frailty was measured using criteria developed in the Cardiovascular
      Health Study, and depressive symptoms were measured using the eight-item Center
      for Epidemiologic Studies Depression scale. RESULTS: Frailty and depression were
      best modeled as two distinct but highly correlated constructs with three and four
      classes of symptom response, respectively. Measurement overlap was high in men
      and women. Approximately 73% of individuals with severe depressive symptoms and
      86% with primarily somatic depressive symptoms were categorized as concurrently
      frail. The degree of construct overlap between depression and frailty did not
      significantly vary according to sex, but women were significantly more likely to
      endorse all frailty and depressive symptoms. CONCLUSION: Measures of depression
      and frailty identify substantially overlapping populations of older men and
      women. More-frequent endorsement of depressive symptoms, but not differential
      endorsement of somatic symptoms, may contribute to the higher prevalence of
      frailty in women. The symptom of exhaustion is particularly important to the
      correlation between these two conditions. Findings will inform clinician and
      researcher efforts to refine the definition of geriatric syndromes such as
      frailty and to develop effective interventions.

PMID- 24576098
TI  - Paradoxical response to disseminated non-tuberculosis mycobacteriosis treatment
      in a patient receiving tumor necrosis factor-alpha inhibitor: a case report.
AB  - BACKGROUND: Biological agents such as tumor necrosis factor-alpha inhibitors are
      known to cause mycobacterium infections. Here, we report a disseminated non
      tuberculosis case caused by TNF-alpha inhibitor therapy and a probable
      paradoxical response to antimycobacterial therapy. CASE PRESENTATION: A 68-year
      old man with relapsing polychondritis was refractory to glucocorticoid therapy;
      adalimumab was therefore administered in combination with oral glucocorticoids.
      Treatment with 40 mg of adalimumab led to rapid improvement of his clinical
      manifestations. The administration of tacrolimus (1 mg) was started as the dosage
      of oral glucocorticoids was tapered. However, the patient developed an
      intermittent high fever and productive cough 15 months after starting adalimumab
      treatment. A chest computed tomography scan revealed new granular shadows and
      multiple nodules in both lung fields with mediastinal lymphadenopathy, and
      Mycobacterium intracellulare was isolated from 2 sputum samples; based on these
      findings, the patient was diagnosed with non-tuberculosis mycobacteriosis.
      Tacrolimus treatment was discontinued and oral clarithromycin (800 mg/day),
      rifampicin (450 mg/day), and ethambutol (750 mg/day) treatment was initiated.
      However, his condition continued to deteriorate despite 4 months of treatment;
      moreover, paravertebral and subcutaneous abscesses developed and increased the
      size of the mediastinal lymphadenopathy. Biopsy of the mediastinal
      lymphadenopathy and a subcutaneous abscess of the right posterior thigh indicated
      the presence of Mycobacterium avium complex (MAC), and the diagnosis of
      disseminated non-tuberculosis mycobacteriosis was confirmed. Despite 9 months of
      antimycobacterial therapy, the mediastinal lymphadenopathy and paravertebral and
      subcutaneous abscesses had enlarged and additional subcutaneous abscesses had
      developed, although microscopic examinations and cultures of sputum and
      subcutaneous abscess samples yielded negative results. We considered this a
      paradoxical reaction similar to other reports in tuberculosis patients who had
      discontinued biological agent treatments, and increased the dose of oral
      glucocorticoids. The patient's symptoms gradually improved with this increased
      dose and his lymph nodes and abscesses began to decrease in size. CONCLUSIONS:
      Clinicians should consider the possibility of a paradoxical response when the
      clinical manifestations of non-tuberculosis mycobacteriosis worsen in spite of
      antimycobacterial therapy or after discontinuation of tumor necrosis factor-alpha
      inhibitors. However, additional evidence is needed to verify our findings and to
      determine the optimal management strategies for such cases.

PMID- 24576099
TI  - Referrals to a new pediatric palliative care team: details of the first 12 months
      of operation.
AB  - BACKGROUND: Although the field of pediatric palliative care (PPC) remains in its
      infancy, over the past decade it has grown in practice and scope. We report on
      patient referral patterns to a new PPC team at a free-standing children's
      hospital. OBJECTIVE: Our aim is to provide a descriptive comparison of the
      patient population seen by our new program as compared to existing literature.
      METHODS: We examined our database of patient referral and demographic data and
      compared our data with published reports. CONCLUSIONS: Our team was operating
      beyond its predicted year-one volume with a patient population that mirrored
      larger, more established programs. In an era of growth and acceptance of PPC,
      hospitals that have undergone a strong needs assessment, significant educational
      effort, and have a strong prediction of patient volume should expect to be
      operating at projected capacity quickly.

PMID- 24576100
TI  - Commentary on: DeLisi M. An empirical study of rape in the context of multiple
      murder. J Forensic Sci 2013; doi: 10.1111/1556-4029.12335.

PMID- 24576094
TI  - RBR E3 ubiquitin ligases: new structures, new insights, new questions.
AB  - The RBR (RING-BetweenRING-RING) or TRIAD [two RING fingers and a DRIL (double
      RING finger linked)] E3 ubiquitin ligases comprise a group of 12 complex
      multidomain enzymes. This unique family of E3 ligases includes parkin, whose
      dysfunction is linked to the pathogenesis of early-onset Parkinson's disease, and
      HOIP (HOIL-1-interacting protein) and HOIL-1 (haem-oxidized IRP2 ubiquitin ligase
      1), members of the LUBAC (linear ubiquitin chain assembly complex). The RBR E3
      ligases share common features with both the larger RING and HECT (homologous with
      E6-associated protein C-terminus) E3 ligase families, directly catalysing
      ubiquitin transfer from an intrinsic catalytic cysteine housed in the C-terminal
      domain, as well as recruiting thioester-bound E2 enzymes via a RING domain.
      Recent three-dimensional structures and biochemical findings of the RBRs have
      revealed novel protein domain folds not previously envisioned and some surprising
      modes of regulation that have raised many questions. This has required renaming
      two of the domains in the RBR E3 ligases to more accurately reflect their
      structures and functions: the C-terminal Rcat (required-for-catalysis) domain,
      essential for catalytic activity, and a central BRcat (benign-catalytic) domain
      that adopts the same fold as the Rcat, but lacks a catalytic cysteine residue and
      ubiquitination activity. The present review discusses how three-dimensional
      structures of RBR (RING1-BRcat-Rcat) E3 ligases have provided new insights into
      our understanding of the biochemical mechanisms of these important enzymes in
      ubiquitin biology. 

PMID- 24576101
TI  - Uranium reduction by Shewanella oneidensis MR-1 as a function of NaHCO3
      concentration: surface complexation control of reduction kinetics.
AB  - It is crucial to determine the controls on the kinetics of U(VI) bioreduction in
      order to understand and model the fate and mobility of U in groundwater systems
      and also to enhance the effectiveness of U bioremediation strategies. In this
      study, we measured the rate of U(VI) reduction by Shewanella oneidensis strain MR
      1 as function of NaHCO3 concentration. The experiments demonstrate that
      increasing concentrations of NaHCO3 in the system lead to slower U(VI) reduction
      kinetics. The NaHCO3 concentration also strongly affects the speciation of U(VI)
      on the bacterial cell envelope. We used a thermodynamic surface complexation
      modeling approach to determine the speciation and concentration of U(VI) adsorbed
      onto the bacteria as a function of the NaHCO3 concentration in the experimental
      systems. We observed a strong positive correlation between the measured U(VI)
      reduction rates and the calculated total concentration of U(VI) surface complexes
      formed on the bacterial cell envelope. This positive correlation indicates that
      the speciation and concentration of U(VI) adsorbed on the bacterial cell envelope
      control the kinetics of U(VI) bioreduction under the experimental conditions. The
      results of this study serve as a basis for developing speciation-based kinetic
      rate laws for enzymatic reduction of U(VI) by bacteria. 

PMID- 24576102
TI  - Controlling dissociation of alkyl phenyl ketone radical cations in the strong
      field regime through hydroxyl substitution position.
AB  - The hydroxy-substituted alkyl phenyl ketones 2'-, 3'- and 4'- (ortho, meta, and
      para) hydroxyacetophenone were excited in the strong-field regime with
      wavelengths ranging from 1200-1500 nm to produce the respective radical cations.
      For 2'- and 3'-hydroxyacetophenone, the parent molecular ion dominated the mass
      spectrum, and the intensity of the fragment ions remained unchanged as a function
      of excitation wavelength. In contrast, 4'-hydroxyacetophenone exhibited depletion
      of the parent molecular ion with corresponding enhanced formation of the benzoyl
      fragment ion upon excitation with 1370 nm as compared with other excitation
      wavelengths. Density functional (DFT) calculations suggest that dissociation
      occurs when the acetyl group in 4'-hydroxyacetophenone radical cation twists out
      of-plane with respect to the phenyl ring, enabling a one-photon transition
      between the ground cation state D0 and the excited cation state D2 to occur. The
      DFT calculations also suggest that the lack of dissociation in the wavelength
      resolved strong-field excitation measurements for 2'- and 3'-hydroxyacetophenone
      arises because both isomers have a barrier to rotation about the carbon-carbon
      bond connecting the phenyl and acetyl groups. These results help elucidate the
      effects of substituents on the torsional motion of radical cations and illustrate
      the potential for controlling molecular dissociation through the addition of
      substituents. 

PMID- 24576103
TI  - Addressing analytical requirements to support health claims on "olive oil
      polyphenols" (EC Regulation 432/2012).
AB  - A health claim on "olive oil polyphenols", namely, hydroxytyrosol and its
      derivatives, was recently approved by EC Regulation 432/2012. As no official
      method exists so far for the complete separation of all forms of hydroxytyrosol
      and tyrosol present in the oil, it is of utmost importance to find a simple,
      reproducible, and undisputable protocol to protect consumers and avoid unfair
      competition. In this study two hydrolysis protocols for the complex forms either
      in the polar fraction of the oil (protocol 1) or directly in the oil (protocol 2)
      were comparatively applied to a series of extra virgin olive oils. Protocol 1
      gave at least 50% higher levels of total hydroxytyrosol and tyrosol.
      Nevertheless, the minimum amount of 5 mg/20 g oil of phenols was fulfilled only
      when suitable correction factors were introduced in the calculations to account
      for the differences in the mass between simple and complex phenols. Changes in
      the terminology used in the health claim are also proposed. 

PMID- 24576104
TI  - Multilayer interparticle linking hybrid MOF-199 for noninvasive enrichment and
      analysis of plant hormone ethylene.
AB  - Ethylene, an important plant hormone, is of utmost importance during many
      developmental processes of plants. However, the efficient enrichment and analysis
      of trace ethylene still remains a challenge. A simple and mild multilayer
      interparticle linking strategy was proposed to fabricate a novel hybrid MOF-199
      enrichment coating. Strong chemical interparticle linkages throughout the coating
      improved the durability and reproducibility of hybrid MOF-199 coating
      dramatically. This coating performed a significant extraction superiority of
      ethylene over commonly used commercial coatings, attributed to the multiple
      interactions including "molecular sieving effect", hydrogen bonding, open metal
      site interaction, and pi-pi affinity. The hybridization of multiwalled carbon
      nanotubes (MWCNTs) with MOF-199 further improved the enrichment capability and
      also acted as a hydrophobic "shield" to prevent the open metal sites of MOF-199
      from being occupied by water molecules, which effectively improved the moisture
      resistant property of MOF-199/CNTs coating. Finally, this novel enrichment method
      was successfully applied for the noninvasive analysis of trace ethylene,
      methanol, and ethanol from fruit samples with relatively high humidity. The low
      detection limit was 0.016 MUg/L for ethylene. It was satisfactory that trace
      ethylene could be actually detected from fruit samples by this noninvasive
      method. Good recoveries of spiked grape, wampee, blueberry, and durian husk
      samples were obtained in the range of 90.0-114%, 79.4-88.6%, 78.5-86.8%, and 85.2
      105% with the corresponding relative standard deviations of 4.8-9.8%, 6.9-8.9%,
      3.8-8.1%, and 9.3-10.5% (n = 3), respectively. 

PMID- 24576105
TI  - Why group & save? Blood transfusion at low-risk elective caesarean section.
AB  - Women undergoing elective caesarean section (CS) routinely have a group and save
      ordered as part of their preoperative assessment, whereas women with expected
      vaginal birth do not. Our aim was therefore to determine the rate of blood
      transfusion at elective CS compared with vaginal birth in a large Australian
      maternity hospital. A retrospective cohort study was performed using routinely
      collected de-identified data of 35 477 women, over 4 years, who delivered at the
      Mater Mothers' Hospital, Brisbane, Australia. After excluding women with
      established risk factors for transfusion, the likelihood of blood transfusion
      following elective CS was significantly lower compared to vaginal birth (aOR 0.47
      (0.29, 0.77)). 

PMID- 24576107
TI  - Increased delivery stride length places greater loads on the ankle joint in elite
      male cricket fast bowlers.
AB  - The purpose of this study was to investigate the effect stride length has on
      ankle biomechanics of the leading leg with reference to the potential risk of
      injury in cricket fast bowlers. Ankle joint kinematic and kinetic data were
      collected from 51 male fast bowlers during the stance phase of the final delivery
      stride. The bowling cohort comprised national under-19, first class and
      international-level athletes. Bowlers were placed into either Short, Average or
      Long groups based on final stride length, allowing statistical differences to be
      measured. A multivariate analysis of variance with a Bonferroni post-hoc
      correction (alpha = 0.05) revealed significant differences between peak
      plantarflexion angles (Short-Long P = 0.005, Average and Long P = 0.04) and
      negative joint work (Average-Long P = 0.026). This study highlighted that during
      fast bowling the ankle joint of the leading leg experiences high forces under
      wide ranges of movement. As stride length increases, greater amounts of negative
      work and plantarflexion are experienced. These increases place greater loads on
      the ankle joint and move the foot into positions that make it more susceptible to
      injuries such as posterior impingement syndrome.

PMID- 24576108
TI  - Standards and guidelines for telemedicine--an evolution.

PMID- 24576106
TI  - Perceptions of family criticism and warmth and their link to symptom expression
      in racially/ethnically diverse adolescents and young adults at clinical high risk
      for psychosis.
AB  - AIM: Little is known about the role of expressed emotion (EE) in early symptom
      expression in individuals at clinical high risk (CHR) for psychosis. In patients
      with established schizophrenia, the effects of EE on clinical outcomes have
      purportedly varied across racial/ethnic groups, but this has not yet been
      investigated among CHR patients. Furthermore, studies have traditionally focused
      upon caregiver levels of EE via interview-based ratings, whereas the literature
      on patient perceptions of caregiver EE on psychosis symptoms is relatively
      limited. METHODS: Linear regression models were conducted to examine the impact
      of criticism and perceived warmth in the family environment, from the CHR
      patient's perspective, on positive and negative symptom expression in non-Latino
      white (NLW; n = 38) and Latino (n = 11) adolescents and young adults at CHR for
      developing psychosis. RESULTS: Analyses examining the sample as a whole
      demonstrated that perceived levels of maternal criticism were negatively
      associated with negative CHR symptomatology. Additional analyses indicated that
      race/ethnicity moderated the relationship between criticism/warmth and clinical
      symptomatology. We found evidence of a contrasting role of patient perceived
      criticism and warmth depending upon the patient's race/ethnicity. CONCLUSION:
      Family processes shown to impact the course of schizophrenia among NLWs may
      function differently among Latino than NLW patients. These findings have
      important implications for the development of culturally appropriate
      interventions and may aid efforts to improve the effectiveness of mental health
      services for diverse adolescents and young adults at CHR for psychosis. Given the
      small sample size of this study, analyses should be replicated in a larger study
      before more definitive conclusions can be made.

PMID- 24576109
TI  - A comparison pressure pain threshold in pericranial and extracephalic regions in
      children with migraine.
AB  - BACKGROUND: There is evidence that the pressure pain threshold (PPT) is reduced
      in children with migraine and that it varies according to age, sex, and region of
      the body. However, in view of the lack of consensus in the literature, the
      objective of the present study was to evaluate the PPT in children with migraine
      of both genders aged 6-12 years. METHODS: Fifty children with migraine without
      aura and 50 children without headache were studied. The PPT was evaluated using
      an algometer at nine bilateral anatomical sites. RESULTS: Comparison of children
      with migraine to children without headache did not show differences in PPT,
      except for the points of insertion of occipital muscles and the anterior aspect
      of C5-C7, where the values were lower in the children with migraine. Analysis
      according to gender revealed that both girls and boys had a lower PPT in at least
      one region evaluated. CONCLUSION: Comparison of the PPTs between sites revealed
      that the pericranial and cervical regions showed a lower PPT than the
      extracephalic sites in children with migraine.

PMID- 24576110
TI  - Energy landscape of the Michaelis complex of lactate dehydrogenase: relationship
      to catalytic mechanism.
AB  - Lactate dehydrogenase (LDH) catalyzes the interconversion between pyruvate and
      lactate with nicotinamide adenine dinucleotide (NAD) as a cofactor. Using isotope
      edited difference Fourier transform infrared spectroscopy on the "live" reaction
      mixture (LDH.NADH.pyruvate ? LDH.NAD(+).lactate) for the wild-type protein and a
      mutant with an impaired catalytic efficiency, a set of interconverting
      conformational substates within the pyruvate side of the Michaelis complex tied
      to chemical activity is revealed. The important structural features of these
      substates include (1) electronic orbital overlap between pyruvate's C2?O bond and
      the nicotinamide ring of NADH, as shown from the observation of a delocalized
      vibrational mode involving motions from both moieties, and (2) a characteristic
      hydrogen bond distance between the pyruvate C2?O group and active site residues,
      as shown by the observation of at least four C2?O stretch bands indicating
      varying degrees of C2?O bond polarization. These structural features form a
      critical part of the expected reaction coordinate along the reaction path, and
      the ability to quantitatively determine them as well as the substate population
      ratios in the Michaelis complex provides a unique opportunity to probe the
      structure-activity relationship in LDH catalysis. The various substates have a
      strong variance in their propensity toward on enzyme chemistry. Our results
      suggest a physical mechanism for understanding the LDH-catalyzed chemistry in
      which the bulk of the rate enhancement can be viewed as arising from a stochastic
      search through an available phase space that, in the enzyme system, involves a
      restricted ensemble of more reactive conformational substates as compared to the
      same chemistry in solution. 

PMID- 24576112
TI  - Intrauterine balloon occlusion during cesarean hysterectomy for placenta previa
      accreta: the internal or common iliac artery?

PMID- 24576111
TI  - Potential non-T cells source of interleukin-4 in food allergy.
AB  - BACKGROUND: Recently, a study from the Consortium of Food Allergy Research
      (CoFAR) showed that allergen-induced IL-4 expression in CD25(+) mononuclear cells
      was increased in allergic patients. However, they did not find the expected
      increase in GATA-3 expression, suggesting that allergen-induced IL-4 might not be
      of T-cell origin. We sought to determine whether other cell types were
      responsible for the increased IL-4 expression in the CD25(+) cell population.
      METHODS: Comparing six allergic patients and six healthy controls, we analyzed
      the CD25(+) isolated population from PBMC for the presence of potential IL-4
      expressing non-T cells. We also compared spontaneous expression levels of surface
      markers (CD203c, CD63, CD25, and HLA-DR) on basophils from whole blood of 42
      peanut-allergic patients and from 12 non-atopic controls. Expression of these
      markers was also evaluated following basophil activation in eight peanut-allergic
      patients selected from the previous cohort. RESULTS: In addition to CD4(+) T
      cells, a substantial proportion of non-T cells were found in the CD25(+) 
      isolated cell population: basophils, NK, and NK-T cells with a mean percentage +/
      s.e.m. of 5.24 +/- 0.63%, 6.65 +/- 1.01%, and 6.01 +/- 1.04%, respectively. The
      majority of these cells exhibited positive intracytoplasmic staining for IL-4.
      Expression of CD63 and CD25 was significantly higher in allergic patients
      compared with controls (p < 0.05). Interestingly, we found a significantly higher
      proportion of activated basophils expressing HLA-DR, compared with non-activated
      basophils (p < 0.05). CONCLUSIONS: Our results support the suggested key role of
      non-T cells secreting IL-4 in food allergy, particularly basophils, which may
      also play a central role in antigen presentation.

PMID- 24576113
TI  - An explanatory analysis of economic and health inequality changes among Mexican
      indigenous people, 2000-2010.
AB  - INTRODUCTION: Mexico faces important problems concerning income and health
      inequity. Mexico's national public agenda prioritizes remedying current
      inequities between its indigenous and non-indigenous population groups. This
      study explores the changes in social inequalities among Mexico's indigenous and
      non-indigenous populations for the time period 2000 to 2010 using routinely
      collected poverty, welfare and health indicator data. METHODS: We described
      changes in socioeconomic indicators (housing condition), poverty (Foster-Greer
      Thorbecke and Sen-Shorrocks-Sen indexes), health indicators (childhood stunting
      and infant mortality) using diverse sources of nationally representative data.
      RESULTS: This analysis provides consistent evidence of disparities in the Mexican
      indigenous population regarding both basic and crucial developmental indicators.
      Although developmental indicators have improved among the indigenous population,
      when we compare indigenous and non-indigenous people, the gap in socio-economic
      and developmental indicators persists. CONCLUSIONS: Despite a decade of efforts
      to promote public programs, poverty persists and is a particular burden for
      indigenous populations within Mexican society. In light of the results, it would
      be advisable to review public policy and to specifically target future policy to
      the needs of the indigenous population.

PMID- 24576114
TI  - Leadership and management challenges in addressing the dignity and respect
      agenda.

PMID- 24576115
TI  - Valuing dignity in patients in a vegetative state on an intensive rehabilitation
      ward: improvement project.
AB  - AIM: To identify the causes that could hinder the provision of dignified care to
      patients in a vegetative state. BACKGROUND: In Italy, the incidence and
      prevalence of people in a vegetative state are increasing. The team members have
      a clear understanding of the meaning of being mortal and the value of human
      dignity. METHODS: A descriptive study design was used in an intensive care ward
      in Northern Italy. An anonymous list with negative factors must be drawn up.
      RESULTS: Thirty-two team members participated in the study. A lack of time and
      specific knowledge regarding the care of patients in a vegetative state,
      involvement of the family and repetition in assistance delivery were the most
      frequent causes that hinder provision of care to patients in a vegetative state.
      DISCUSSION AND CONCLUSIONS: The provision of dignity for patients is not an issue
      related only to the staff in direct contact with patients/clients, but also
      concerns the entire health care facility (physical structure and organisation).
      IMPLICATIONS FOR NURSING MANAGEMENT: The nursing coordinator has an important
      role in the promotion of care based on the respect for the patient's dignity, in
      the active involvement of staff and in the delivery of quality services to users.

PMID- 24576116
TI  - Transitions in a wicked environment.
AB  - AIM: The aim of this review is to synthesize the current body of knowledge
      concerning transitional care for patients 65 years of age and older moving from
      the acute care setting to home. BACKGROUND: Transitional care is a timely topic
      as hospital days of care decrease whereas patient needs grow more complex as a
      result of aging populations. EVALUATION: This review considers evidence-based
      research as well as reports, case studies and literature reviews related to
      transitional care. International articles are included. KEY ISSUES: The authors
      explore transitional care through the lens of wicked problems; problems that
      appear seemingly intractable and are characterized by inter-related dilemmas,
      contradictory agendas, and multi-layered societal, economic and political
      influences. Outcome measures of success, barriers to achieving successful
      transitional care and effectiveness of interventions are investigated.
      CONCLUSIONS: While the literature offers specific strategies that positively
      affect transitional care, there are few strategies that do not negatively affect
      an alternate agenda. Conscientious leaders should consider transitional care in
      the context of its wicked nature in order to achieve optimal patient care.
      IMPLICATIONS: Stakeholders include: hospital administrators, nurse leaders,
      direct-care nurses, acute care and primary care clinicians, patients, caregivers,
      community agencies, health sciences educators and insurers.

PMID- 24576117
TI  - The importance of relational coordination for integrated care delivery to older
      patients in the hospital.
AB  - AIM: This study investigated relational coordination among professionals
      providing healthcare to hospitalized older patients and assessed its impact on
      integrated care delivery. BACKGROUND: Previous studies have shown that relational
      coordination is positively associated with the delivery of acute, emergency and
      trauma care. The effect of relational coordination in integrated care delivery to
      hospitalized older patients remains unknown. METHODS: This cross-sectional study
      was part of an examination of integrated care delivery to hospitalized older
      patients. Data were collected using questionnaires distributed to hospital
      professionals (192 respondents; 44% response rate). RESULTS: After controlling
      for demographic variables, regression analyses showed that relational
      coordination was positively related to integrated care delivery (beta = 0.20; P
      <= 0.05). Relational coordination was lower among professionals in the same
      discipline, and higher between nurses and others than between medical specialists
      and others. Relational coordination and integrated care delivery were
      significantly higher in geriatrics than in other units (both P <= 0.001).
      CONCLUSIONS: The enhancement of relational coordination among healthcare
      professionals is positively associated with integrated care delivery to older
      patients. IMPLICATIONS FOR NURSING MANAGEMENT: Relational coordination should be
      improved between medical specialists and others and higher levels of relational
      coordination and integrated care delivery should be achieved in all hospital
      units.

PMID- 24576118
TI  - Letter to the Editor: charge nurse education: impact on job performance and
      satisfaction.

PMID- 24576119
TI  - Letter to the Editor: in response to 'bullying and the older nurse'.

PMID- 24576120
TI  - Letter to the Editor: nurse manager succession planning: synthesis of evidence.

PMID- 24576121
TI  - Stochastic measures of network resilience: applications to waterway commodity
      flows.
AB  - Given the ubiquitous nature of infrastructure networks in today's society, there
      is a global need to understand, quantify, and plan for the resilience of these
      networks to disruptions. This work defines network resilience along dimensions of
      reliability, vulnerability, survivability, and recoverability, and quantifies
      network resilience as a function of component and network performance. The
      treatment of vulnerability and recoverability as random variables leads to
      stochastic measures of resilience, including time to total system restoration,
      time to full system service resilience, and time to a specific alpha% resilience.
      Ultimately, a means to optimize network resilience strategies is discussed,
      primarily through an adaption of the Copeland Score for nonparametric stochastic
      ranking. The measures of resilience and optimization techniques are applied to
      inland waterway networks, an important mode in the larger multimodal
      transportation network upon which we rely for the flow of commodities. We provide
      a case study analyzing and planning for the resilience of commodity flows along
      the Mississippi River Navigation System to illustrate the usefulness of the
      proposed metrics. 

PMID- 24576122
TI  - What professional curiosity can bring you.

PMID- 24576123
TI  - Vitamin D supplementation for diffuse musculoskeletal pain: results of a before
      and-after study.
AB  - BACKGROUND: Several studies have shown that vitamin D supplementation could be
      useful for treating diffuse musculoskeletal (DMS) pain in adults. OBJECTIVES: The
      aim of this study was to evaluate the effects of correcting a vitamin D
      deficiency (<= 50 nmol/l) on DMS pain and quality of life in adults. METHODS: A
      pragmatic prospective study was conducted in a general practice setting in the
      Rhone-Alps area between 1 February and 30 April 2009. Patients between the ages
      of 18 and 50 years old who consulted their general practitioner (GP) for DMS pain
      or chronic unexplained asthenia and had a deficient serum 25 (OH) D level with no
      signs of any other disease were enrolled in this study. The patients received
      high doses of vitamin D supplements (400 000 to 600 000 units). Mean pain
      evaluation scores were evaluated before and after vitamin D supplementation using
      mixed models and accounting for repeated measures. RESULTS: Before vitamin D
      supplementation, the adult study cohort (n = 49) had an adjusted mean serum 25
      (OH) D level of 23.7 nmol/l, a mean pain evaluation score of 5.07 and a mean
      quality of life score of 3.55. After vitamin D supplementation, the adjusted mean
      serum 25 (OH) D level increased to 118.8 nmol/l (P < 0.001), the mean quality of
      life score increased to 2.8 nmol/l (P < 0.001) and the mean pain evaluation score
      decreased to 2.8 (P < 0.001). CONCLUSION: In this small before-and-after study,
      vitamin D supplementation decreased pain scores in adult patients with diffuse
      musculoskeletal pain and vitamin D deficiency. These results must be confirmed by
      further studies.

PMID- 24576124
TI  - General practitioners' perceptions of their role in cancer follow-up care: a
      qualitative study in the Netherlands.
AB  - BACKGROUND: In the last few decades there has been a considerable increase in the
      number of cancer survivors. Health policy makers would like to see cancer follow
      up care moved from secondary to primary care. METHOD: Between 2008 and 2010, a
      qualitative study among primary health care professionals was performed to get
      more insight into the way they care for cancer survivors. Analysed was whether a
      coordinating role in cancer survivorship care would fit in with the practical
      logic underlying the way the general practitioners work. RESULTS: In their
      everyday work, general practitioners are used to provide care in a reactive way.
      Based on this habitus, they classify their patients into 'not special' and
      'special' ones. Since general practitioners label cancer survivors as 'not
      special,' they expect these patients to take the initiative to ask for help and
      present their complaints in a clear and complete way. Their habitus as a
      gatekeeper implies that they are reticent about referring patients to other
      primary health care professionals. In regard to 'not special' patients, such as
      cancer survivors, general practitioners appear to build on the patients' own
      strengths. CONCLUSION: The emphasis on a wait-and-see attitude in contemporary
      Dutch general practice, as well as the general practitioners' role as a
      gatekeeper are at odds with the proactive and holistic approach inherent to a
      coordinating role in cancer follow-up. Therefore, we assume that it will be
      difficult for general practitioners to shape a pivotal role in this care.

PMID- 24576128
TI  - EGPRN: European General Practice Research Network The EGPRN Autumn 2013 Meeting
      in Malta.

PMID- 24576125
TI  - The non-clinical contents of GP training need more attention. Results from the
      Finnish Physician Study.
AB  - BACKGROUND: The competencies required of a GP are complex and ever-expanding. GP
      training should adequately cover all the content areas. OBJECTIVES: The aim was
      to assess GPs' and GP trainees' satisfaction with their specialist training and
      with the contents of training. Trends in assessments over a ten-year period were
      investigated. METHODS: Data from Finnish national surveys of physicians conducted
      in 1998, 2003 and 2008 were analysed with 606, 457 and 324 GPs and GP trainees
      respectively being sampled in the present study. Respondents were asked how
      satisfied they were with their own specialist training in general, and how much
      instruction they had received in 12 specific areas during their specialist
      training. RESULTS: Satisfaction with GP training slowly increased during the
      study years. In 2008, 59% of respondents were satisfied with their training,
      compared to 46% in 1998. The best covered content area was clinical work. Major
      shortcomings were reported in many of the content areas analysed, e.g. management
      and leadership. CONCLUSION: Although the trend in satisfaction with GP training
      in Finland is for the better, there are shortcomings, especially in many of the
      non-clinical content areas of training. More attention needs to be paid to these
      areas in the future.

PMID- 24576130
TI  - Euripa: The European Rural And Isolated Practitioners Association Euripa 5th
      Rural Health Forum. Riga, Latvia, 26-28 September 2014. Rural Family Medicine
      today and tomorrow.

PMID- 24576129
TI  - Egprn-Euripa. Working together - raising the profile of rural research.

PMID- 24576131
TI  - EUROPREV: European Network for Prevention and Health Promotion in Family Medicine
      & General Practice EUROPREV news 2013.

PMID- 24576132
TI  - IPCRG:International Primary Care Respiratory Group IPCRG World Conference,
      International Research Collaboration, Asthma Resources and Motivation for Flu
      Vaccination.

PMID- 24576133
TI  - EFPC: European Forum for Primary Care Latest Update on the Primary Care Lobby in
      Europe and Beyond!

PMID- 24576134
TI  - The international primary care research training curriculum.

PMID- 24576137
TI  - Review of international early psychosis programmes and a model to overcome unique
      challenges to the treatment of early psychosis in the United States.
AB  - AIM: This article presents a literature review of treatments for first-episode
      psychosis throughout the world and describes the POTENTIAL (Patient-Oriented
      Treatment for Early or New onset schizophrenia To Initiate A Long-term recovery)
      Early Psychosis Programme in detail, explaining the model and the rationale, as
      well as the uniqueness of the programme. METHODS: An international search was
      conducted for English articles using PubMed, PsycINFO and PsycARTICLES, as well
      as the reference lists of published studies and reviews. One article that is
      currently in press was included, which was not part of the original literature
      search. Inclusion criteria included any published or in press study focused upon
      treatment programmes for early psychosis. Out of the 62 articles collected, 27
      publications met this criterion and were utilized. In addition to identifying
      clinical programmes, gaps in treatment for this population were identified.
      RESULTS: The primary method in the United States for the treatment of early
      psychosis is randomized trial for new pharmacological treatments where patients
      are research subjects. Although there are a multitude of both research and
      clinical programmes internationally, the few programmes that exist in the United
      States that focus upon first-episode psychosis are either research based or focus
      upon prodromal symptoms. Clinical programmes such as the POTENTIAL programme are
      nearly non-existent. CONCLUSIONS: Although the POTENTIAL programme has been
      successful both clinically and financially, there are still more strides to be
      taken to improve upon young adult services. Future development of the programme
      is continuing with the incorporation of outcome data and outreach into the
      community.

PMID- 24576138
TI  - Infants track word forms in early word-object associations.
AB  - A central component of language development is word learning. One
      characterization of this process is that language learners discover objects and
      then look for word forms to associate with these objects (Mcnamara, 1984; Smith,
      2000). Another possibility is that word forms themselves are also important, such
      that once learned, hearing a familiar word form will lead young word learners to
      look for an object to associate with it (Juscyzk, 1997). This research
      investigates the relative weighing of word forms and objects in early word-object
      associations using the anticipatory eye-movement paradigm (AEM; McMurray & Aslin,
      2004). Eighteen-month-old infants and adults were taught novel word-object
      associations and then tested on ambiguous stimuli that pitted word forms and
      objects against each other. Results revealed a change in weighing of these
      components across development. For 18-month-old infants, word forms weighed more
      in early word-object associative learning, while for adults, objects were more
      salient. Our results suggest that infants preferentially use word forms to guide
      the process of word-object association.

PMID- 24576136
TI  - Age-related decreases of serum-response factor levels in human mesenchymal stem
      cells are involved in skeletal muscle differentiation and engraftment capacity.
AB  - Skeletal muscle (SkM) comprise ~40% of human body weight. Injury or damage to
      this important tissue can result in physical disability, and in severe cases is
      difficult for its endogenous stem cell-the satellite cell-to reverse effectively.
      Mesenchymal stem cells (MSC) are postnatal progenitor/stem cells that possess
      multilineage mesodermal differentiation capacity, including toward SkM. Adult
      bone marrow (BM) is the best-studied source of MSCs; however, aging also
      decreases BMMSC numbers and can adversely affect differentiation capacity.
      Therefore, we asked whether human sources of developmentally early stage
      mesenchymal stem cells (hDE-MSCs) isolated from embryonic stem cells, fetal bone,
      and term placenta could be cellular sources for SkM repair. Under standard muscle
      inducing conditions, hDE-MPCs differentiate toward a SkM lineage rather than
      cardiomyocytic or smooth muscle lineages, as evidenced by increased expression of
      SkM-associated markers and in vitro myotube formation. In vivo transplantation
      revealed that SkM-differentiated hDE-MSCs can efficiently incorporate into host
      SkM tissue in a mouse model of SkM injury. In contrast, adult BMMSCs do not
      express SkM-associated genes after in vitro SkM differentiation nor engraft in
      vivo. Further investigation of possible factors responsible for this difference
      in SkM differentiation potential revealed that, compared with adult BMMSCs, hDE
      MSCs expressed higher levels of serum response factor (SRF), a transcription
      factor critical for SkM lineage commitment. Moreover, knockdown of SRF in hDE
      MSCs resulted in decreased expression of SkM-related genes after in vitro
      differentiation and decreased in vivo engraftment. Our results implicate SRF as a
      key factor in age-related SkM differentiation capacity of MSCs, and demonstrate
      that hDE-MSCs are possible candidates for SkM repair. 

PMID- 24576139
TI  - Effect of body mass index on latency periods after history-indicated cervical
      cerclage.
AB  - BACKGROUND: The impact of maternal body mass index (BMI) on cervical cerclage
      outcomes is not clear in the literature. AIM: We sought to investigate the impact
      of BMI on history-indicated cervical cerclage outcomes in our unit. METHODS: We
      retrospectively reviewed 196 history-indicated cervical cerclage procedures. The
      results were analysed according to the BMI groups <25, 25-30 and >=30 kg/m(2) .
      RESULTS: A total of 122 cases were available for the final analysis. Thirty-two
      (26.1%) of the women had normal BMI (BMI < 25), 69 (56.5%) were overweight (BMI =
      25-30) and 21 (17.4%) were obese (BMI >= 30). The mean gestational age of
      delivery according to BMI groups <25, 25-30 and >=30 were 37.2 +/- 3.1, 36.0 +/-
      5.3 and 36.0 +/- 4.9 weeks (P = 0.591), respectively. The mean latency periods
      according to BMI groups <25, 25-30 and >=30 were 24.3 +/- 3.2, 21.1 +/- 5.1 and
      21.4 +/- 4.9 weeks (P = 0.171), respectively. We found no correlation between the
      BMI and latency periods (Spearman's rho = -0.252). The multivariable logistic
      regression model found no variable to affect preterm birth rates. CONCLUSIONS:
      The BMI has no impact on history-indicated cervical cerclage procedure outcomes.
      Normal weight, overweight and obese women had similar latency periods after
      history-indicated cervical cerclage. This high percentage of preterm birth risk
      necessitates close surveillance of these women for preterm birth.

PMID- 24576141
TI  - Optical spectroscopy of the bulk and interfacial hydrated electron from ab initio
      calculations.
AB  - The optical spectrum of the hydrated (aqueous) electron, e(aq)(-), is the primary
      observable by means of which this species is detected, monitored, and studied. In
      theoretical calculations, this spectrum has most often been simulated using one
      electron models. Here, we present ab initio simulations of that spectrum in both
      bulk water and, for the first time, at the water/vapor interface, using density
      functional theory and its time-dependent variant. Our results indicate that this
      approach provides a reliable description, and quantitative agreement with the
      experimental spectrum for the bulk species is obtained using a "tuned" long-range
      corrected functional. The spectrum of the interfacial electron is found to be
      very similar to the bulk spectrum.

PMID- 24576142
TI  - The influence of various confounding factors on mechanical nociceptive thresholds
      in the donkey.
AB  - OBJECTIVE: To evaluate a mechanical nociceptive threshold (MNT) testing device in
      the donkey, and to investigate the influence of potential confounders on MNTs
      generated. STUDY DESIGN: Prospective, randomised. ANIMALS: Sixteen castrated male
      donkeys aged 4-9 years, weighing 105-170 kg. METHODS: Mechanical nociceptive
      thresholds were measured using an actuator with three pins placed on the dorsal
      aspect of the distal limb, connected to a force meter. The pins (surface area 15
      mm(2) ) were extruded onto the limb by pressurising an air-filled syringe, until
      the MNT force (when foot-lift was observed) or 25 N (cut-off force) was reached.
      Effect on MNT of presence of a companion donkey, the limb tested, rate of
      application of force, testing location, level of distraction, ambient temperature
      and hair cover at the test site was evaluated. Long and short-term repeatability
      of MNT was assessed. Data were analysed using general linear models and Mann
      Whitney U tests, p < 0.05 was considered significant. RESULTS: Increasing the
      rate of force application significantly increased the mean +/- SD MNT from 9.2 +/
      2.0 N when applied at 0.4 N sec(-1) to 10.6 +/- 2.1 N when applied at 1.2 N sec(
      1) (p = 0.001). No other factors significantly influenced MNT. Mean MNT remained
      stable over a 3 week period, however MNTs were significantly (p = 0.006) higher
      (12.8 +/- 3.0 N cf 10.3 +/- 1.9 N) after a 12 month interval. CONCLUSIONS AND
      CLINICAL RELEVANCE: When designing studies measuring MNT in donkeys, rate of
      application of force must be standardised. Donkeys' MNTs have good short-term
      stability suggesting this technique is appropriate for short-term analgesiometry
      studies; however variability of MNTs over the long-term is greater.

PMID- 24576143
TI  - A three-season comparison of match performances among selected and unselected
      elite youth rugby league players.
AB  - This study compared technical actions, movements, heart rates and perceptual
      responses of selected and unselected youth rugby league players during matches
      (under-15 to under-17 age groups). The players' movements and heart rates were
      assessed using 5 Hz Global Positioning Systems (GPSs), while their technical
      actions were analysed using video analysis. The maturity of each player was
      predicted before each season for statistical control. There were no differences
      (P > 0.05) between selected and unselected players in the under-15 or the under
      17 age group for any variables. However, in the under-16 age group, the selected
      players (57.1 +/- 11.9 min) played for longer than the unselected players (44.1
      +/- 12.3 min; P = 0.017; ES = 1.08 +/- CI = 0.87), and covered more distance
      (5181.0 +/- 1063.5 m cf. 3942.6 +/- 1108.6 m, respectively; P = 0.012; ES = 1.14
      +/- CI = 0.88) and high-intensity distance (1808.8 +/- 369.3 m cf. 1380.5 +/-
      367.7 m, respectively; P = 0.011; ES = 1.16 +/- CI = 0.88). Although successful
      carries per minute was higher in the selected under-15 age group, there were no
      other differences (P > 0.05) in match performance relative to playing minutes
      between groups. Controlling for maturity, the less mature, unselected players
      from the under-16 age group performed more high-intensity running (P < 0.05). Our
      findings question the use of match-related measurements in differentiating
      between selected and unselected players, showing that later maturing players were
      unselected, even when performing greater high-intensity running during matches.

PMID- 24576140
TI  - The association between geographic proximity to a dialysis facility and use of
      dialysis catheters.
AB  - BACKGROUND: Residing remotely from health care resources appears to impact
      quality of care delivery. It remains unclear if there are differences in vascular
      access based on distance of one's residence to dialysis centre at time of
      dialysis initiation, and whether region or duration of pre-dialysis care are
      important effect modifiers. METHODS: We studied the association of distance from
      a patients' residence to the nearest dialysis centre and central venous catheter
      (CVC) use in an observational study of 26,449 incident adult dialysis patients
      registered in the Canadian Organ Replacement Registry between 2000-2009.
      Multivariate logistic regression was used to assess the association between
      distance in tertiles and CVC use, adjusted for patient demographics and
      comorbidities. Geographic region and duration of pre-dialysis care were examined
      as potential effect modifiers. RESULTS: Eighty percent of patients commenced
      dialysis with a CVC. Incident CVC use was highest among those living > 20 km from
      the dialysis centre (OR 1.29 (1.24-1.34)) compared to those living < 5 km from
      centre. The length of pre-dialysis care and geographic region were significant
      effect modifiers; among patients residing in the furthest tertile (>20 km) from
      the nearest dialysis centre, incident CVC use was more common with shorter length
      of pre-dialysis care (< 1 year) and residence in central regions of the country.
      CONCLUSION: Residing further from a dialysis centre is associated with increased
      CVC use, an effect modified by shorter pre-dialysis care and the geographic
      region of the country. Efforts to reduce geographical disparities in pre dialysis
      care may decrease CVC use.

PMID- 24576144
TI  - MVAPACK: a complete data handling package for NMR metabolomics.
AB  - Data handling in the field of NMR metabolomics has historically been reliant on
      either in-house mathematical routines or long chains of expensive commercial
      software. Thus, while the relatively simple biochemical protocols of metabolomics
      maintain a low barrier to entry, new practitioners of metabolomics experiments
      are forced to either purchase expensive software packages or craft their own data
      handling solutions from scratch. This inevitably complicates the standardization
      and communication of data handling protocols in the field. We report a newly
      developed open-source platform for complete NMR metabolomics data handling,
      MVAPACK, and describe its application on an example metabolic fingerprinting data
      set. 

PMID- 24576145
TI  - Conversation analysis of the two-chair self-soothing task in emotion-focused
      therapy.
AB  - OBJECTIVE: Despite an increasing recognition of the relevance and significance of
      self-compassion processes, little research has explored interventions that seek
      to enhance these in therapy. In this study, we examined the compassionate self
      soothing task of emotion-focused therapy involving two-chair work, with seven
      clients. METHOD: Conversation analysis was used to examine client-therapst
      interaction. RESULTS: The analysis yielded a detailed description of
      interactional practices and processes involved in the accomplishment of self
      soothing, drawing on Goffman's concept of the participation frame. We show how
      therapists and clients collaborate to move from the ordinary frame of therapeutic
      conversation to a self-soothing frame and back again by using various
      interactional practices: Therapists' instructions to clients, specific ways of
      sequencing actions in interaction, explanations and justification of the
      importance of the self-soothing task, pronouns as a way to distinguish among
      addressees (e.g., clients versus soothing agents), corrections of clients' talk,
      and response tokens (hm mm, yeah, good). These practices are used to help clients
      accomplish self-soothing in the form of self-praise, disclosing caring, and
      offering of helpful advice. CONCLUSIONS: This study offers therapists a specific
      account of how to respond to clients at specific junctures in self-soothing
      dialogues and how to structure and accomplish the self-soothing task.

PMID- 24576147
TI  - Inducing single molecule magnetic behavior in a [Co4O4] cubane via a pronounced
      solvatomagnetic effect.
AB  - The pyrazole-based tridentate diol ligand 2-(1-(2-hydroxyethyl)-1H-pyrazol-3
      yl)phenol (H2L) forms a cubane-type complex [Co4L4(MeOH)4] (1) that features a
      {Co4O4} core and four exogenous MeOH ligands. Electrospray ionization mass
      spectrometry suggests that the MeOH ligands are easily lost, and
      thermogravimetric analysis evinces a thermally induced release of those methanol
      molecules from solid material in the temperature range from 380 to 440 K.
      Desolvation was found to give rise to a pronounced solvatomagnetic effect that
      causes a switching of the spin ground state of the {Co4O4} core from diamagnetic
      to magnetic. Furthermore, the desolvated "naked" [Co4L4] cube (1*) shows slow
      relaxation of the magnetization and butterfly-like magnetic hysteresis at 2 K. A
      comparatively high relaxation barrier Ueff/kB = 64.4 K and a characteristic
      relaxation time tau0 = 3.8 * 10(-9) s for 1* have been derived from an Arrhenius
      plot. These findings thus demonstrate that the emergence of interesting magnetic
      properties in molecule-based materials can be triggered via a solvatomagnetic
      process, even for materials that in their solvated form have a diamagnetic (ST =
      0) ground state. 

PMID- 24576146
TI  - The taccalonolides and paclitaxel cause distinct effects on microtubule dynamics
      and aster formation.
AB  - BACKGROUND: Microtubule stabilizers suppress microtubule dynamics and, at the
      lowest antiproliferative concentrations, disrupt the function of mitotic
      spindles, leading to mitotic arrest and apoptosis. At slightly higher
      concentrations, these agents cause the formation of multiple mitotic asters with
      distinct morphologies elicited by different microtubule stabilizers. RESULTS: We
      tested the hypothesis that two classes of microtubule stabilizing drugs, the
      taxanes and the taccalonolides, cause the formation of distinct aster structures
      due, in part, to differential effects on microtubule dynamics. Paclitaxel and the
      taccalonolides suppressed the dynamics of microtubules formed from purified
      tubulin as well as in live cells. Both agents suppressed microtubule dynamic
      instability, with the taccalonolides having a more pronounced inhibition of
      microtubule catastrophe, suggesting that they stabilize the plus ends of
      microtubules more effectively than paclitaxel. Live cell microscopy was also used
      to evaluate the formation and resolution of asters after drug treatment. While
      each drug had similar effects on initial formation, substantial differences were
      observed in aster resolution. Paclitaxel-induced asters often coalesced over time
      resulting in fewer, larger asters whereas numerous compact asters persisted once
      they were formed in the presence of the taccalonolides. CONCLUSIONS: We conclude
      that the increased resistance of microtubule plus ends to catastrophe may play a
      role in the observed inability of taccalonolide-induced asters to coalesce during
      mitosis, giving rise to the distinct morphologies observed after exposure to
      these agents.

PMID- 24576148
TI  - Evaluation of the interdisciplinary PSYMEPHY treatment on patients with
      fibromyalgia: a randomized control trial.
AB  - OBJECTIVE: Fibromyalgia (FM) is a chronic disorder that can have a devastating
      effect on patients' lives. This study assessed the efficacy of a 6-week
      interdisciplinary treatment that combines coordinated PSYchological, Medical,
      Educational, and PHYsiotherapeutic interventions (PSYMEPHY) compared with
      standard pharmacologic care. DESIGN: The study was a randomized controlled trial
      (54 participants in the PSYMEPHY group and 56 in the control group [CG] ) with
      follow-up at 6 months. PSYMEPHY patients were also assessed at 12 months. The
      main outcomes were changes in total Fibromyalgia Impact Questionnaire (FIQ)
      score, pain, fatigue, morning tiredness, anxiety, and use of pain coping
      strategies as measured by the FIQ, the visual analog scale, and the Coping with
      Chronic Pain Questionnaire. After the 6-month assessment, patients in the CG were
      offered the PSYMEPHY treatment, and completed all of the instruments immediately
      after treatment, and at 6- and 12-month follow-up visits (N = 93). SETTING:
      Subjects received therapy at two different outpatient clinical locations.
      PATIENTS: Fibromyalgia patients. RESULTS: Six months after the intervention,
      significant improvements in total FIQ score (P = 0.04), and pain (P = 0.03) were
      seen in the PSYMEPHY group compared with controls. Twelve months after the
      intervention, all patients in the PSYMEPHY group maintained statistically
      significant improvements in total FIQ score, and pain, and showed an improvement
      in fatigue, rested, anxiety, and current pain compared with baseline. Data from
      the control patients who underwent the PSYMEPHY intervention corroborated the
      initial results. CONCLUSIONS: This study highlights the beneficial effects of an
      interdisciplinary treatment for FM patients in a hospital pain management unit. A
      6-week interdisciplinary intervention showed significant improvement in key
      domains of fibromyalgia, as quality of life, pain, fatigue, rested, and anxiety
      at 12 months.

PMID- 24576149
TI  - Animal protein intake is associated with higher-level functional capacity in
      elderly adults: the Ohasama study.
AB  - OBJECTIVES: To determine the association between protein intake and risk of
      higher-level functional decline in older community-dwelling adults. DESIGN:
      Prospective. SETTING: Ohasama Town, Japan. PARTICIPANTS: Residents (N = 1,007;
      mean age 67.4 +/- 5.5) free of functional decline at baseline; follow-up was
      conducted for 7 years. MEASUREMENTS: Nutrient and food intakes were determined
      using a validated 141-item food frequency questionnaire. Participants were
      divided into quartiles according to intake levels of total, animal, and plant
      protein. Subscales of the Tokyo Metropolitan Institute of Gerontology Index of
      Competence subscales were used to assess higher-level functional decline.
      Logistic regression analysis was used to examine the future risk of higher-level
      functional decline in relation to protein intake, with lowest protein intake as
      reference. RESULTS: During the study period, 24.4% of eligible participants
      reported declines in higher-level functional capacity. After adjustment for
      putative confounding factors, men in the highest quartile of animal protein
      intake had significantly lower risk of higher-level functional decline than those
      in the lowest quartile (odds ratio (OR) = 0.41, 95% confidence interval (CI) =
      0.20-0.83; P for trend .01). These associations were not seen in women (OR =
      0.76, 95% CI = 0.41-1.34; P for trend .37). No consistent association was
      observed between plant protein intake and future higher-level functional decline
      in either sex. CONCLUSION: Higher protein, particularly animal protein, was
      associated with lower risk of decline in higher-level functional capacity in
      older men. Animal protein intake may be a modifiable indicator for early
      detection and prevention of higher-level functional decline in elderly adults.

PMID- 24576151
TI  - Target-cell-specific fluorescence silica nanoprobes for imaging and theranostics
      of cancer cells.
AB  - MicroRNAs (miRNAs) has been identified as diagnostic and prognostic biomarkers
      and predictors of drug response for many diseases, including a broad range of
      cancers, heart disease, and neurological diseases. The noninvasive theranostics
      system for miRNAs is very important for diagnosis and therapy of the cellular
      disease. Herein, a target-cell-specific theranostics nanoprobe for target-cell
      specific delivery, cancer cells and intracellular miRNA-21 imaging, and cancer
      cell growth inhibition was proposed. The nanoprobe (FS-AS/MB) was prepared by
      simultaneously coupling of the AS1411 aptamer and miRNA-21 molecular beacon (miR
      21-MB) onto the surface of Ru(bpy)32+-encapsulated silica (FS) nanoparticles. The
      FS nanoparticles synthesized by a facile reverse microemulsion method showed
      nearly monodisperse spherical shape with a smooth surface, good colloidal
      stability, a fluorescence quantum yield of ~21%, and low cytotoxicity. The
      antibiofouling polymer PEG grafted onto a silica shell reduced nonspecific uptake
      of cells. The ability of FS-AS/MB for target-specific cells delivery,
      simultaneous cancer cells, intracellular miRNA-21 imaging, and inhibition of
      miRNA-21 function and suppression of cell growth in vitro, were also
      demonstrated. The results of the present study suggested that the proposed
      nanoprobes would be a promising theranostics for different cancers by imaging and
      inhibiting other intracellular genes.

PMID- 24576150
TI  - Cord blood LC-PUFA composition and allergic diseases during the first 10 yr.
      Results from the LISAplus study.
AB  - BACKGROUND: It has been suggested that n-6 and n-3 long-chain polyunsaturated
      fatty acids (LC-PUFAs) in blood are associated with risk of allergic diseases,
      although results are inconclusive. Low levels of n-6 LC-PUFA and high levels of n
      3 LC-PUFA are anticipated to have beneficial effects. Pregnancy is considered a
      critical time period for imprinting the developing immune system. We examined
      whether n-6 LC-PUFA, n-3 LC-PUFA concentrations or the n-6/n-3 ratio in cord
      blood (CB) serum are associated with allergic diseases up to the age of 10 yr.
      METHODS: This analysis included 436 children from the Munich LISAplus birth
      cohort study. Information on doctor-diagnosed asthma, hay fever/allergic
      rhinitis, and eczema was collected using questionnaires completed at the ages 6
      and 10 yr, and for eczema additionally at 2 yr. Specific immunoglobulin E (IgE)
      against inhalant allergens was measured at 6 and 10 yr. Fatty acid composition
      was measured by gas chromatography in serum from CB and from blood collected at
      2, 6, and 10 yr. Associations between n-3, n-6 LC-PUFA concentrations, and the n
      6/n-3 ratio in CB serum and allergic diseases or atopy were assessed using
      generalized estimating equations (GEE) considering the longitudinal structure.
      Models were adjusted for LC-PUFA concentrations at follow-up and potential
      confounding factors. RESULTS: There was no significant association between n-3 LC
      PUFA, n-6 LC-PUFA, or the n-6/n-3 ratio in CB serum with eczema, asthma, hay
      fever/allergic rhinitis, or aeroallergen sensitization. CONCLUSIONS: There is no
      indication of a beneficial effect of increased n-3 LC-PUFA in CB serum on the
      development of any of the disease entities.

PMID- 24576152
TI  - Spatial and cellular characterization of mTORC1 activation after spinal cord
      injury reveals biphasic increase mainly attributed to microglia/macrophages.
AB  - Mechanistic target of rapamycin complex 1 (mTORC1) is an intracellular kinase
      complex that regulates energy homeostasis and transcription. Modulation of mTORC1
      has proven beneficial in experimental spinal cord injury, making this molecular
      target a candidate for therapeutic intervention in spinal cord injury. However,
      both inactivation and activation of mTORC1 have been reported beneficial for
      recovery. To obtain a more complete picture of mTORC1 activity, we aimed to
      characterize the spatiotemporal activation pattern of mTORC1 and identify
      activation in particular cell types after contusion spinal cord injury in rats.
      To be able to provide a spatial characterization of mTORC1 activation, we
      monitored activation of downstream target S6. We found robust mTORC1 activation
      both at the site of injury and in spinal segments rostral and caudal to the
      injury. There was constitutive mTORC1 activation in neurons that was biphasically
      reduced caudally after injury. We found biphasic mTORC1 activation in glial
      cells, primarily activated microglia/macrophages. Furthermore, we found mTORC1
      activation in proliferating cells, suggesting this may be a function affected by
      mTORC1 modulation. Our results reveal potential windows of opportunity for
      therapeutic interference with mTORC1 signaling and immune cells as targets for
      inhibition of mTORC1 in spinal cord injury. 

PMID- 24576153
TI  - Exposure factors for wastewater-irrigated Asian vegetables and a probabilistic
      rotavirus disease burden model for their consumption.
AB  - Many farmers in water-scarce regions of developing countries use wastewater to
      irrigate vegetables and other agricultural crops, a practice that may expand with
      climate change. There are a number of health risks associated with wastewater
      irrigation for human food crops, particularly with surface irrigation techniques
      common in the developing world. The World Health Organization (WHO) recommends
      using quantitative microbial risk assessment (QMRA) to determine if the
      irrigation scheme meets health standards. However, only a few vegetables have
      been studied for wastewater risk and little information is known about the
      disease burden of wastewater-irrigated vegetable consumption in China. To bridge
      this knowledge gap, an experiment was conducted to determine volume of water left
      on Asian vegetables and lettuce after irrigation. One hundred samples each of
      Chinese chard (Brassica rapa var. chinensis), Chinese broccoli (Brassica oleracea
      var. alboglabra), Chinese flowering cabbage (Brassica rapa var. parachinensis),
      and lettuce (Lactuca sativa) were harvested after overhead sprinkler irrigation.
      Chinese broccoli and flowering cabbage were found to capture the most water and
      lettuce the least. QMRAs were then constructed to estimate rotavirus disease
      burden from consumption of wastewater-irrigated Asian vegetables in Beijing.
      Results indicate that estimated risks from these reuse scenarios exceed WHO
      guideline thresholds for acceptable disease burden for wastewater use, signifying
      that reduction of pathogen concentration or stricter risk management is necessary
      for safe reuse. Considering the widespread practice of wastewater irrigation for
      food production, particularly in developing countries, incorporation of water
      retention factors in QMRAs can reduce uncertainty regarding health risks for
      consumers worldwide. 

PMID- 24576154
TI  - Is x-ray compulsory in pubic symphysis diastasis diagnosis?

PMID- 24576155
TI  - Mechanism of quinolone action and resistance.
AB  - Quinolones are one of the most commonly prescribed classes of antibacterials in
      the world and are used to treat a variety of bacterial infections in humans.
      Because of the wide use (and overuse) of these drugs, the number of quinolone
      resistant bacterial strains has been growing steadily since the 1990s. As is the
      case with other antibacterial agents, the rise in quinolone resistance threatens
      the clinical utility of this important drug class. Quinolones act by converting
      their targets, gyrase and topoisomerase IV, into toxic enzymes that fragment the
      bacterial chromosome. This review describes the development of the quinolones as
      antibacterials, the structure and function of gyrase and topoisomerase IV, and
      the mechanistic basis for quinolone action against their enzyme targets. It will
      then discuss the following three mechanisms that decrease the sensitivity of
      bacterial cells to quinolones. Target-mediated resistance is the most common and
      clinically significant form of resistance. It is caused by specific mutations in
      gyrase and topoisomerase IV that weaken interactions between quinolones and these
      enzymes. Plasmid-mediated resistance results from extrachromosomal elements that
      encode proteins that disrupt quinolone-enzyme interactions, alter drug
      metabolism, or increase quinolone efflux. Chromosome-mediated resistance results
      from the underexpression of porins or the overexpression of cellular efflux
      pumps, both of which decrease cellular concentrations of quinolones. Finally,
      this review will discuss recent advancements in our understanding of how
      quinolones interact with gyrase and topoisomerase IV and how mutations in these
      enzymes cause resistance. These last findings suggest approaches to designing new
      drugs that display improved activity against resistant strains.

PMID- 24576156
TI  - Treatment satisfaction, adherence and behavioral assessment in patients de
      escalating from natalizumab to interferon beta.
AB  - BACKGROUND: De-escalating natalizumab (NTZ) to interferon beta 1b (IFN B 1B) is a
      possible treatment option in multiple sclerosis (MS) patients interrupting NTZ
      because of increased risk of progressive multifocal leukoencephalopathy (PML).
      The aim of this study was to evaluate satisfaction and adherence to treatment,
      behavioral and fatigue changes in patients switched to IFN B 1B compared to
      continued NTZ treatment. METHODS: A 1 year, prospective, randomized, rater
      blinded, parallel-group study. Nineteen relapsing remitting (RR) MS patients,
      randomly assigned to undergo either NTZ (n = 10) or IFN B 1B (n = 9) treatment,
      who had previously received NTZ for at least 12 months with disease stability and
      fearing or at risk for PML were included. Patients underwent behavioral and
      treatment assessments at baseline, after 24-week and 1 year follow-up. Behavioral
      assessment included measures of cognition, fatigue and quality of life. Treatment
      assessment included measures of satisfaction, persistence and adherence to
      treatment. Clinical-radiological disease activity and safety were also assessed.
      RESULTS: Baseline characteristics of patients were similar between groups except
      for Euro Quality Visual Analogue Scale, being higher in the NTZ group (p = 0.04).
      Within-group comparisons at the three time points, as well as interaction
      analysis of treatment effect over time did not show any statistically significant
      differences in behavioral or treatment assessments, but a coherent trend favoring
      NTZ over IFN B 1B. CONCLUSIONS: De-escalating NTZ to IFN B 1B is feasible and
      associated with overall good patient related outcome and persistently stable
      behavioral measures.

PMID- 24576158
TI  - Analgesic and gastrointestinal effects of epidural morphine in horses after
      laparoscopic cryptorchidectomy under general anesthesia.
AB  - OBJECTIVE: To evaluate the hypothesis that epidural morphine (0.1 mg kg(-1) )
      decreases pain in horses after laparoscopic surgery without adversely affecting
      gastrointestinal (GI) motility. STUDY DESIGN: Randomized clinical trial. ANIMALS:
      Eighteen horses undergoing laparoscopic cryptorchidectomy under general
      anesthesia. METHODS: Horses were randomly assigned to receive either epidural
      morphine (0.1 mg kg(-1) ) or no epidural before the start of surgery. Pain
      behaviors were assessed during the first two post-operative days using a
      numerical rating scale. Barium-filled spheres were administered through a
      nasogastric tube before anesthesia. GI motility was assessed by recording manure
      production, by quantitating the spheres in the manure, and by abdominal
      auscultation of intestinal sounds. Heart rates and cortisol concentrations were
      also measured during the post-operative period. RESULTS: Pain scores increased
      for 12 hours after surgery in the control group and were significantly higher
      than in the morphine group for the first 6 hours. Pain scores remained unaltered
      in the morphine group throughout the observation period. Heart rate and plasma
      cortisol concentrations did not differ between groups or with time. No signs of
      colic were observed in any horse. CONCLUSION AND CLINICAL RELEVANCE: Epidural
      morphine (0.1 mg kg(-1) ) did not adversely affect GI motility in horses after
      laparoscopic surgery under general anesthesia.

PMID- 24576157
TI  - Siderophores in environmental research: roles and applications.
AB  - Siderophores are organic compounds with low molecular masses that are produced by
      microorganisms and plants growing under low iron conditions. The primary function
      of these compounds is to chelate the ferric iron [Fe(III)] from different
      terrestrial and aquatic habitats and thereby make it available for microbial and
      plant cells. Siderophores have received much attention in recent years because of
      their potential roles and applications in various areas of environmental
      research. Their significance in these applications is because siderophores have
      the ability to bind a variety of metals in addition to iron, and they have a wide
      range of chemical structures and specific properties. For instance, siderophores
      function as biocontrols, biosensors, and bioremediation and chelation agents, in
      addition to their important role in weathering soil minerals and enhancing plant
      growth. The aim of this literature review is to outline and discuss the important
      roles and functions of siderophores in different environmental habitats and
      emphasize the significant roles that these small organic molecules could play in
      applied environmental processes. 

PMID- 24576162
TI  - Theoretical studies on two-dimensional nonlinear optical chromophores with
      pyrazinyl cores and organic or ruthenium(II) ammine electron donors.
AB  - Density functional theory calculations have been carried out on twelve cationic,
      2D nonlinear optical chromophores with pyrazinylbis(pyridinium) electron
      acceptors. These species contain either 4-(methoxy/dimethylamino)phenyl or
      pyridyl-coordinated {Ru(II)(NH3)5}(2+)/trans-{Ru(II)(NH3)4(py)}(2+) (py =
      pyridine) electron donor groups. The results are compared with data obtained by
      using experimental techniques including hyper-Rayleigh scattering and Stark
      (electroabsorption) spectroscopy previously (Coe, B. J.; et al. Inorg. Chem.
      2010, 49, 10718; J. Org. Chem. 2010, 75, 8550). The B3LYP/6-311G(d) level of
      theory models the visible absorption spectra in MeCN for the -NMe2 derivatives
      relatively well, whereas CAM-B3LYP/6-311G(d) gives better results for the -OMe
      substituted species. These spectra are dominated by intramolecular charge
      transfer (ICT) bands. Static first hyperpolarizabilities beta0 are computed also
      at the B3LYP/6-311G(d) level. The overall extent of prediction of trends in the
      ICT bands and beta0 responses is partial, with the main discrepancies relating to
      the progression from one to two electron donor groups. The experimental data show
      that this structural change red-shifts the ICT bands and increases beta0
      significantly, but only the second trend is reproduced to some extent by the
      calculations. The UV-vis absorption spectra of the Ru complexes in MeCN are
      modeled relatively well with B3LYP and the LANL2DZ/6-311G(d) mixed basis set,
      including 100 excited states. However, again, some degree of disagreement between
      theory and experiment is evident, even when a larger basis set like def2-TZVP is
      used for Ru. In particular, substantial red shifts are predicted on adding a
      third metal center, whereas the measured spectra show corresponding small blue
      shifts. The experimental trend of the total beta0 value increasing on moving from
      one to two Ru centers is predicted in the gas phase, but not in MeCN. For both
      classes of chromophore, the beta(xxx) tensor component dominates in the
      asymmetric species, whereas beta(xxy) is the largest component for their 2-fold
      symmetric counterparts.

PMID- 24576161
TI  - Parameter-based assessment of disturbed and intact components of visual attention
      in children with developmental dyslexia.
AB  - People with developmental dyslexia (DD) have been shown to be impaired in tasks
      that require the processing of multiple visual elements in parallel. It has been
      suggested that this deficit originates from disturbed visual attentional
      functions. The parameter-based assessment of visual attention based on Bundesen's
      () theory of visual attention allows one to identify and quantify the underlying
      deficits. The present study provides the first groupwise comparison between
      children with DD (n = 12; mean age 9.84 years) and typically developing children
      (n = 12; mean age 9.87 years) with regard to intact and disturbed components of
      visual attention. From the performance on whole- and partial-report tasks, we
      derived individual parameter estimates of four different parameters: visual
      processing speed, storage capacity of visual short-term memory (VSTM), laterality
      of attentional weighting and efficiency of top-down control. Groupwise
      comparisons revealed that general attentional resources, processing speed and
      VSTM storage capacity, are impaired in children with DD compared to typically
      developing children. In contrast, selectivity parameters, laterality of
      attentional selection and attentional top-down control did not differ between
      these groups. Relating the current findings to previous results, obtained in
      highly comparable methodological settings, from single cases of children with DD,
      and from a group of adults with DD, we conclude that slowed perceptual processing
      speed is a primary visual attentional deficit in DD. Furthermore, reduced VSTM
      storage capacity seems to modulate the difficulties in written language
      processing imposed by the disorder.

PMID- 24576160
TI  - Can amphipathic helices influence the CNS antinociceptive activity of
      glycopeptides related to beta-endorphin?
AB  - Glycosylated beta-endorphin analogues of various amphipathicity were studied in
      vitro and in vivo in mice. Opioid binding affinities of the O-linked
      glycopeptides (mono- or disaccharides) and unglycosylated peptide controls were
      measured in human receptors expressed in CHO cells. All were pan-agonists,
      binding to MU-, delta-, or kappa-opioid receptors in the low nanomolar range (2.2
      35 nM K(i)'s). The glycoside moiety was required for intravenous (i.v.) but not
      for intracerebroventricular (i.c.v.) activity. Circular dichroism and NMR
      indicated the degree of helicity in H2O, aqueous trifluoroethanol, or micelles.
      Glycosylation was essential for activity after i.v. administration. It was
      possible to manipulate the degree of helicity by the alteration of only two amino
      acid residues in the helical address region of the beta-endorphin analogues
      without destroying MU-, delta-, or kappa-agonism, but the antinociceptive
      activity after i.v. administration could not be directly correlated to the degree
      of helicity in micelles.

PMID- 24576163
TI  - Pelvic inflammatory disease in women with endometriosis is more severe than in
      those without.
AB  - AIMS: To determine the incidence and severity of acute pelvic inflammatory
      disease (PID) or tubo-ovarian abscess (TOA) in hospitalised women with and
      without a history of endometriosis. METHODS: Retrospective analysis of hospital
      records retrieved for all women hospitalised with PID or TOA between January 2008
      and December 2011 in a tertiary referral centre. Women were compared with regard
      to a history of endometriosis for demographic, clinical and fertility data.
      RESULTS: 26 (15%) of the 174 women hospitalised due to PID or TOA were excluded
      because of age older than 45 years, leaving 148 for analysis. The mean age was
      35.7 +/- 9.3 years and mean duration of hospitalisation was 5.9 +/- 3.7 days. The
      women were divided into two groups: Group 1 with endometriosis (n = 21) and Group
      2 without endometriosis (n = 127). Women in Group 1 as compared with Group 2 were
      significantly more likely to have undergone a fertility procedure prior to being
      admitted to the hospital with PID (9/27 (45%) vs 22/121 (17%), P < 0.001);
      particularly in vitro fertilisation (IVF) (7/ 27 (33%) vs 12/121 (9%), P <
      0.006); Women in Group 1 more frequently experienced a severe and complicated
      course involving longer duration of hospitalisation (8.8 +/- 4.7 vs 4.4 +/- 2.3
      days, P < 0.0001) and antibiotic treatment failure (10/27 (48%) vs 8/121 (6%), P
      < 0.0001). CONCLUSIONS: Pelvic inflammatory disease in women with endometriosis
      is more severe and refractory to antibiotic treatment, often requiring surgical
      intervention. It is likely that endometriosis is a risk factor for the
      development of severe PID, particularly after IVF treatment.

PMID- 24576164
TI  - The state of the union on treatment of acute myeloid leukemia.

PMID- 24576166
TI  - Visceral leishmaniasis mimicking Richter transformation.

PMID- 24576165
TI  - Thalidomide, clarithromycin, lenalidomide and dexamethasone therapy in newly
      diagnosed, symptomatic multiple myeloma.
AB  - We studied T-BiRD (thalidomide [Thalomid((r))], clarithromycin [Biaxin((r))],
      lenalidomide [Revlimid((r))] and dexamethasone) in symptomatic, newly diagnosed
      multiple myeloma. In 28-day cycles, patients received dexamethasone 40 mg/day on
      days 1, 8, 15, 22, clarithromycin 500 mg twice daily on days 1-28; lenalidomide
      25 mg/day on days 1-21; and thalidomide 100 mg/day (50 mg/day on days 1-7 of
      cycle 1 only) on days 1-28. Twenty-six patients received a median of 6 cycles
      (range 0-41). Overall response rate (ORR) was 80% for the group and 100% in 11
      patients who underwent autologous stem cell transplantation as part of first-line
      therapy. The 4-year overall survival rate was 74.9%, and the median progression
      free survival was 35.6 months. Eight patients discontinued due to regimen
      toxicity. Grade 3 non hematologic toxicity affected 12 patients (46.2%). T-BiRD
      is a highly active regimen with potential toxicity limitations.
      ClinicalTrials.gov identifier: NCT00538733.

PMID- 24576167
TI  - Validation of the simplified prognostic score for splenic marginal zone lymphoma
      of the Splenic Marginal Zone Lymphoma Working Group.

PMID- 24576168
TI  - The impact of prehydration on the clearance and toxicity of high-dose
      methotrexate for pediatric patients.
AB  - Abstract High-dose methotrexate (HD-MTX) is an important chemotherapy for various
      pediatric malignancies. However, in contrast to precise recommendations on
      supportive care following the start of HD-MTX infusion, studies on the hydration
      regimen prior to HD-MTX infusion are lacking, and the local standard differs
      between pediatric oncology centers. Therefore, we prospectively evaluated the
      relevance of two common prehydration regimens on the clearance and toxicity of
      MTX in a randomized crossover study. There was no impact of the prehydration
      regimen on plasma levels and toxicity of MTX, but most parents preferred a fast
      prehydration regimen due to a significantly shorter inpatient treatment (mean
      duration 3.39 +/- 0.79 days vs. 4.36 +/- 0.70 days, p < 0.001). Based on our
      results, short prehydration seems safe, and may be recommended prior to the start
      of HD-MTX infusions instead of initiating hydration the preceding day. 

PMID- 24576169
TI  - Auer rod-like inclusions in the cytoplasm of splenic lymphoma cells.

PMID- 24576170
TI  - Low-valent cobalt catalysis: new opportunities for C-H functionalization.
AB  - Rapid progress in the fields of organometallic chemistry and homogeneous
      catalysis has made it possible for synthetic chemists to consider using
      ubiquitous yet unreactive C-H bonds as starting points to construct complex
      organic molecules. However, a majority of the C-H functionalization reactions
      currently in use require noble transition metal catalysts and harsh reaction
      conditions, so researchers have placed a priority on the development of mild and
      cost-effective catalysts. Given this situation, we wondered whether earth
      abundant first-row transition metals could emulate the reactivity of a noble
      transition metal catalyst and carry out similar C-H functionalization reactions
      at a lower cost and under milder conditions. We also wondered whether we could
      use first-row transition metals to achieve hitherto unknown, but useful, C-H
      functionalization reactions. This Account summarizes our research on the
      development of three different types of C-H functionalization reactions using low
      valent cobalt catalysts: (1) hydroarylation of alkynes and olefins, (2) ortho C-H
      functionalization with electrophiles, and (3) addition of arylzinc reagents to
      alkynes involving 1,4-cobalt migration. Although synthetic chemists have
      previously paid little attention to cobalt in designing catalytic C-H
      functionalization reactions, earlier studies, particularly those on
      stoichiometric cyclometalation, inspired us as we developed the hydroarylation
      and ortho C-H functionalization reactions. In these transformations, we combined
      a cobalt precatalyst, a ligand (such as phosphine or N-heterocyclic carbene
      (NHC)), and Grignard reagent to generate low-valent cobalt catalysts. These novel
      catalysts promoted a series of pyridine- and imine-directed hydroarylation
      reactions of alkynes and olefins at mild temperatures. Notably, we observed
      branched-selective addition to styrenes, which highlights a distinct
      regioselectivity of the cobalt catalyst compared with typical rhodium and
      ruthenium catalysts. The combination of a cobalt-NHC catalyst and a Grignard
      reagent allows directed aromatic C-H functionalizations with electrophiles such
      as aldimines, aryl chlorides, and alkyl chlorides or bromides. This second
      reaction has a particularly broad scope, allowing us to introduce secondary alkyl
      groups at the ortho position of aryl imines, a difficult reaction to carry out by
      other means. Serendipitously, we found that a cobalt-Xantphos complex catalyzed
      the third type of C-H functionalization: the addition of an arylzinc reagent to
      an alkyne to afford ortho-alkenylarylzinc species through a 1,4-cobalt migration.
      This "migratory arylzincation" allowed us to quickly construct a diverse group of
      functionalized benzothiophenes and benzoselenophenes. Collectively, our studies
      of cobalt catalysis have provided cost-effective catalysts and milder conditions
      for existing C-H functionalizations and have led to some unprecedented,
      attractive chemical transformations. 

PMID- 24576172
TI  - Cell cycle progression score and treatment decisions in prostate cancer: results
      from an ongoing registry.
AB  - OBJECTIVE: The cell cycle progression (CCP) test (Prolaris) is a novel prognostic
      assay that provides accurate risk of prostate cancer-specific disease progression
      and disease specific mortality when combined with standard clinicopathologic
      parameters. This prospective study evaluated the impact of the CCP report on
      physician treatment recommendations for prostate cancer. METHODS: Physicians
      ordering the CCP test in clinical practice completed surveys regarding treatment
      recommendations before and after they received and discussed the test results
      with patients. Clinicians also rated the influence of the test result on
      treatment decisions. Treatment selections were confirmed via third-party audit of
      patient charts following final survey responses. RESULTS: Overall, 65% of cases
      showed a change between intended treatment pre- and post-CCP test reporting. Pre
      CCP testing, 164 of 305 cases received a recommendation for interventional
      treatment. Post-CCP test, interventional therapy was recommended for 103 of these
      cases, a reduction of 37.2%. Conversely, 141 of 305 cases were recommended pre
      CCP testing for non-interventional treatment; 108 of these remained with non
      interventional treatment while 33 shifted to interventional options, a 23.4%
      increase. There was a 49.5% reduction in surgical interventions and a 29.6%
      reduction in radiation treatment. A third-party audit identified 80.2%
      concordance between the post-CCP testing treatment recommendation and actual
      treatment. Re-assignment to intervention or non-intervention generally correlated
      with the result of the CCP report. Study limitations included physician selection
      of patients for testing, no evaluation of patient input in therapeutic choice,
      and other potential treatment decision factors not queried by the survey.
      CONCLUSION: Based on responses of ordering physicians, the CCP report adds
      meaningful new information to risk assessment for localized prostate cancer
      patients. Test results led to changes in treatment with reductions and increases
      in interventional treatment that were directionally aligned with prostate cancer
      risk specified by the test.

PMID- 24576173
TI  - Engineering of midbrain organoids containing long-lived dopaminergic neurons.
AB  - The possibility to generate dopaminergic (DA) neurons from pluripotent stem cells
      represents an unlimited source of material for tissue engineering and cell
      therapy for neurodegenerative disease. We set up a protocol based on the
      generation of size-calibrated neurospheres for a rapid production (3 weeks) of a
      high amount of DA neurons (>60%) oriented toward a midbrain-like phenotype,
      characterized by the expression of FOXA2, LMX1A, tyrosine hydroxylase (TH),
      NURR1, and EN1. By using gamma-secretase inhibitors and varying culture time of
      neurospheres, we controlled maturation and cellular composition of a three
      dimensional (3D) engineered nervous tissue (ENT). ENT contained neurons and glial
      cells expressing various markers of maturity, such as synaptophysin, neuronal
      nuclei-specific protein (NeuN), and glial fibrillary acidic protein (GFAP), and
      were electrophysiologically active. We found that 3-week-old neurospheres were
      optimal to generate 3D tissue containing DA neurons with typical A9 morphology.
      ENT generated from 4-week-old neurospheres launched glial cell type since
      astrocytes and myelin could be detected massively at the expense of TH
      immunoreactive neurons. All gamma-secretase inhibitors were not equivalent;
      compound E was more efficient than DAPT in generating DA neurons. This DA tissue
      provides a tool for drug screening, and toxicology. It should also become a
      useful biomaterial for studies on Parkinson's disease. 

PMID- 24576175
TI  - A comparison of electromyography and stroke kinematics during ergometer and on
      water rowing.
AB  - This study assessed muscle recruitment patterns and stroke kinematics during
      ergometer and on-water rowing to validate the accuracy of rowing ergometry. Male
      rowers (n = 10; age 21 +/- 2 years, height 1.90 +/- 0.05 m and body mass 83.3 +/-
      4.8 kg) performed 3 * 3 min exercise bouts, at heart and stroke rates equivalent
      to 75, 85 and 95% VO2peak, on both dynamic and stationary rowing ergometers, and
      on water. During exercise, synchronised data for surface electromyography (EMG)
      and 2D kinematics were recorded. Overall muscle activity was quantified by the
      integration of rmsEMG and averaged for each 10% interval of the stroke cycle.
      Muscle activity significantly increased in rectus femoris (RF) and vastus
      medialis (VM) (P <0.01), as exercise intensity increased. Comparing EMG data
      across conditions revealed significantly (P <0.05) greater RF and VM activity
      during on-water rowing at discrete 10% intervals of stroke cycle. In addition,
      the drive/recovery ratio was significantly lower during dynamic ergometry
      compared to on-water (40 +/- 1 vs. 44 +/- 1% at 95%, P <0.01). Results suggest
      that significant differences exist while comparing recruitment and kinematic
      patterns between on-water and ergometer rowing. These differences may be due to
      altered acceleration and deceleration of moving masses on-ergometer not perfectly
      simulating the on-water scenario.

PMID- 24576174
TI  - High calcium concentration in bones promotes bone metastasis in renal cell
      carcinomas expressing calcium-sensing receptor.
AB  - BACKGROUND: The prognosis for renal cell carcinoma (RCC) is related to a high
      rate of metastasis, including 30% of bone metastasis. Characteristic for bone
      tissue is a high concentration of calcium ions. In this study, we show a
      promoting effect of an enhanced extracellular calcium concentration on mechanisms
      of bone metastasis via the calcium-sensing receptor (CaSR) and its downstream
      signaling molecules. METHODS: Our analyses were performed using 33 (11/category)
      matched specimens of normal and tumor tissue and 9 (3/category) primary cells
      derived from RCC patients of the 3 categories: non-metastasized, metastasized
      into the lung and metastasized into bones during a five-year period after
      nephrectomy. Expression of CaSR was determined by RT-PCR, Western blot analyses
      and flow cytometry, respectively. Cells were treated by calcium and the CaSR
      inhibitor NPS 2143. Cell migration was measured in a Boyden chamber with calcium
      (10 MUM) as chemotaxin and proliferation by BrdU incorporation. The activity of
      intracellular signaling mediators was quantified by a phospho-kinase array and
      Western blot. RESULTS: The expression of CaSR was highest in specimens and cells
      of patients with bone metastases. Calcium treatment induced an increased
      migration (19-fold) and proliferation (2.3-fold) exclusively in RCC cells from
      patients with bone metastases. The CaSR inhibitor NPS 2143 elucidated the role of
      CaSR on the calcium-dependent effects. After treatment with calcium, the activity
      of AKT, PLCgamma-1, p38alpha and JNK was clearly enhanced and PTEN expression was
      almost completely abolished in bone metastasizing RCC cells. CONCLUSIONS: Our
      results indicate a promoting effect of extracellular calcium on cell migration
      and proliferation of bone metastasizing RCC cells via highly expressed CaSR and
      its downstream signaling pathways. Consequently, CaSR may be regarded as a new
      prognostic marker predicting RCC bone metastasis.

PMID- 24576176
TI  - Focal palmar keratoderma and leukokeratosis anogenitalis: an extremely rare
      genodermatosis associated with cytokeratine 17 mutation.

PMID- 24576178
TI  - Human and nature-caused hazards: the affect heuristic causes biased decisions.
AB  - People are more concerned about the negative consequences of human hazards
      compared with natural hazards. Results of four experiments show that the same
      negative outcome (e.g., number of birds killed by an oil spill) was more
      negatively evaluated when caused by humans than when caused by nature. Results
      further show that when identical risk information was provided, participants
      evaluated nuclear power more negatively compared with solar power. The affect
      associated with the hazard per se influenced the interpretation of the new
      information. Furthermore, the affect experienced in the situation fully mediated
      the evaluation of the negative outcomes of a hazard. People's reliance on the
      affect heuristic is a challenge for acceptance of cost-benefit analyses because
      equally negative outcomes are differently evaluated depending on the cause.
      Symbolically significant information and the affect evoked by this information
      may result in biased and riskier decisions. 

PMID- 24576179
TI  - Assessing clinical significance using robust normative comparisons.
AB  - OBJECTIVE: Clinical significance determines whether an intervention makes a real
      difference in the everyday life of a client. One of the most recommended
      approaches for conducting group-level analyses of clinical significance is to
      evaluate whether the treated clinical group is equivalent to a normal comparison
      group (normative comparisons). The purpose of this study was to demonstrate the
      analytical and practical power of assessing clinical significance using normative
      comparisons that are robust to violations of normality and homogeneity of
      variance assumptions. METHOD: Six datasets were gleaned from published
      intervention studies for depression. RESULTS: We found that normative comparisons
      using a robust Schuirmann-Yuen test determined equivalency for 11% fewer clinical
      samples compared to original normative comparisons that use a Schuirmann test of
      equivalence. CONCLUSIONS: We recommend that researchers conducting normative
      comparisons utilize the Schuirmann-Yuen procedure as it provides the most
      reliable method available for determining if a treated clinical group is
      equivalent to a normative comparison group.

PMID- 24576180
TI  - Multilayer paper-based device for colorimetric and electrochemical quantification
      of metals.
AB  - The release of metals and metal-containing compounds into the environment is a
      growing concern in developed and developing countries, as human exposure to
      metals is associated with adverse health effects in virtually every organ system.
      Unfortunately, quantifying metals in the environment is expensive; analysis costs
      using certified laboratories typically exceed $100/sample, making the routine
      analysis of toxic metals cost-prohibitive for applications such as occupational
      exposure or environmental protection. Here, we report on a simple, inexpensive
      technology with the potential to render toxic metals detection accessible for
      both the developing and developed world that combines colorimetric and
      electrochemical microfluidic paper-based analytical devices (mPAD) in a three
      dimensional configuration. Unlike previous mPADs designed for measuring metals,
      the device reported here separates colorimetric detection on one layer from
      electrochemical detection on a different layer. Separate detection layers allows
      different chemistries to be applied to a single sample on the same device. To
      demonstrate the effectiveness of this approach, colorimetric detection is shown
      for Ni, Fe, Cu, and Cr and electrochemical detection for Pb and Cd. Detection
      limits as low as 0.12 MUg (Cr) were achieved on the colorimetric layer while
      detection limits as low as 0.25 ng (Cd and Pb) were achieved on the
      electrochemical layer. Selectivity for the target analytes was demonstrated for
      common interferences. As an example of the device utility, particulate metals
      collected on air sampling filters were analyzed. Levels measured with the mPAD
      matched known values for the certified reference samples of collected particulate
      matter. 

PMID- 24576177
TI  - Race and documentation of cognitive impairment in hospitalized older adults.
AB  - OBJECTIVES: To evaluate whether race influences agreement between screening
      results and documentation of cognitive impairment and delirium. DESIGN: Secondary
      data analysis. SETTING: An urban, public hospital and healthcare system.
      PARTICIPANTS: Hospitalized older adults aged 65 and older admitted to general
      inpatient medical services evaluated for cognitive impairment (n = 851) and
      evaluated for delirium (n = 424). MEASUREMENTS: Cognitive impairment and delirium
      were measured in each participant using the Short Portable Mental Status
      Questionnaire (SPMSQ) and the Confusion Assessment Method (CAM), respectively, as
      the reference identification method. Clinical documentation of cognitive
      impairment and delirium was defined according to the presence of International
      Classification of Diseases, Ninth Revision (ICD-9), codes from within 1 year
      before hospitalization through discharge for cognitive impairment or from
      hospital admission through discharge for delirium. RESULTS: Two hundred ninety
      four participants (34%) had cognitive impairment based on SPMSQ performance, and
      163 (38%) had delirium based on CAM results. One hundred seventy-one (20%) of
      those with cognitive impairment had an ICD-9 code for cognitive impairment,
      whereas 92 (22%) of those with delirium had an ICD-9 code for delirium. After
      considering age, sex, education, socioeconomic status, chronic comorbidity, and
      severity of acute illness, of those who screened positive on the SPMSQ, African
      Americans had a higher adjusted odds ratio (AOR) than non-African Americans for
      clinical documentation of cognitive impairment (AOR = 1.66, 95% confidence
      interval (CI) = 0.95-2.89), and of those who screened negative on the SPMSQ,
      African Americans had higher odds of clinical documentation of cognitive
      impairment (AOR = 2.10, 95% CI = 1.17-3.78) than non-African Americans. There
      were no differences in clinical documentation rates of delirium between African
      Americans and non-African Americans. CONCLUSION: Racial differences in coding for
      cognitive impairment may exist, resulting in higher documentation of cognitive
      impairment in African Americans screening positive or negative for cognitive
      impairment.

PMID- 24576181
TI  - MiR-22 is frequently downregulated in medulloblastomas and inhibits cell
      proliferation via the novel target PAPST1.
AB  - Medulloblastoma is the most frequent malignant central nervous system tumor in
      children. MicroRNAs (miRs) are small, non-coding RNAs that target protein-coding
      and non-coding RNAs, and play roles in a variety of cellular processes through
      regulation of multiple targets. In the present study, we analyzed miR-22
      expression and its effect in cell proliferation and apoptosis in
      medulloblastomas. Quantitative reverse transcription PCR (RT-PCR) revealed
      significantly lower expression of miR-22 in 19 out of 27 (70%) medulloblastomas,
      D341, DAOY, ONS-76 medulloblastoma cell lines, compared with normal cerebellum.
      Forced expression of miR-22 by lentiviral vector transfection reduced cell
      proliferation and induced apoptosis, while knockdown of miR-22 increased
      proliferative activity in DAOY and ONS-76 cells. DAOY cells with miR-22
      overexpression in nude mice yielded tumors smaller than those originated from
      control DAOY cells. Microarray analysis in DAOY cells with forced miR-22
      expression showed significant changes in expression profiles, PAPST1 being the
      most significantly (10 folds) downregulated gene. Quantitative RT-PCR revealed
      PAPST1 mRNA upregulation in 18 out of 27 (67%) medulloblastomas. In addition, a
      luciferase reporter assay in ONS-76 and DAOY cells suggested that miR-22 directly
      targets the PAPST1 gene, and lentivirus-mediated knockdown of PAPST1 suppressed
      proliferation of DAOY and ONS-76 medulloblastoma cells. These results suggest
      that frequently downregulated miR-22 expression is associated with cell
      proliferation in medulloblastomas, and this may be at least in part via PAPST1,
      which is a novel target of miR-22. 

PMID- 24576182
TI  - Neural specialization for speech in the first months of life.
AB  - How does the brain's response to speech change over the first months of life?
      Although behavioral findings indicate that neonates' listening biases are
      sharpened over the first months of life, with a species-specific preference for
      speech emerging by 3 months, the neural substrates underlying this developmental
      change are unknown. We examined neural responses to speech compared with
      biological non-speech sounds in 1- to 4-month-old infants using fMRI. Infants
      heard speech and biological non-speech sounds, including heterospecific
      vocalizations and human non-speech. We observed a left-lateralized response in
      temporal cortex for speech compared to biological non-speech sounds, indicating
      that this region is highly selective for speech by the first month of life.
      Specifically, this brain region becomes increasingly selective for speech over
      the next 3 months as neural substrates become less responsive to non-speech
      sounds. These results reveal specific changes in neural responses during a
      developmental period characterized by rapid behavioral changes.

PMID- 24576184
TI  - Presumed 'suicidal right ventricle' in a Cocker Spaniel dog undergoing pulmonary
      valve balloon dilation and its prevention in an analogous case.

PMID- 24576185
TI  - Application of the LUminometric Methylation Assay to ecological species: tissue
      quality requirements and a survey of DNA methylation levels in animals.
AB  - The LUminometric Methylation Assay (LUMA) measures global DNA methylation. LUMA
      depends on digestion of DNA with methyl-sensitive and methyl-insensitive
      restriction enzymes, followed by pyrosequencing. Until recently, LUMA has been
      principally used for biomedical research. Here, we use chickens as a model to
      investigate sample quality issues relating to LUMA and then apply the method to
      ecological species. First, we assessed the effect of tissue storage conditions on
      DNA methylation values. This is an important consideration for ecological species
      because samples are not always ideally preserved and LUMA is sensitive to poor
      DNA quality. We found that good quality LUMA data could be obtained from chicken
      liver and brain tissues stored at 21  degrees C for at least 2 and 12 h,
      respectively. Longer storage times introduced nonspecific peaks to pyrograms
      which were associated with reduced DNA methylation. Repeatedly, freezing and
      thawing the tissues did not affect LUMA data. Second, we measured DNA methylation
      in 12 species representing five animal classes: amphibians (African and Western
      clawed frog), reptiles (green anole lizard), fish (yellow perch, goldfish, lake
      trout), mammals (American mink, polar bear, short-beaked common dolphin, Atlantic
      white-sided dolphin) and birds (chicken, Japanese quail). We saw a pattern of
      high DNA methylation in fish (84-87%), and intermediate levels in mammals (68
      72%) and birds (52-71%). This pattern corresponds well with previous measures of
      DNA methylation generated by HPLC. Our data represent the first CpG methylation
      values to be reported in several species and provide a basis for studying
      patterns of epigenetic inheritance in an ecological context. 

PMID- 24576186
TI  - Microwave spectrum, conformational composition, and dipole moment of
      (fluoromethyl)cyclopropane (C3H5CH2F).
AB  - The microwave spectrum of (fluoromethyl)cyclopropane, C3H5CH2F, has been
      investigated in the whole 12-75.6 GHz spectral range. Many measurements were also
      performed in the 75.6-120 GHz region. The spectra of two conformers were
      assigned. The H-C-C-F chain of atoms is antiperiplanar in the conformer denoted
      ap and synclinal in the sc rotamer. The sc conformer has a lower energy than ap.
      The internal energy difference was determined to be E(ap) - E(sc) = 1.7(8) kJ/mol
      from relative intensity measurements. The spectra of the ground vibrational state
      and seven vibrationally excited states belonging to two different normal modes
      were assigned for sc. The frequencies of these two modes were determined by
      relative intensity measurements. The dipole moment of this conformer was
      determined to be MU(a) = 5.520(17), MU(b) = 3.475(29), MU(c) = 0.35(13), and
      MU(TOT) = 6.532(40) * 10(-30) C m [1.958(12) D]. The spectrum of the ground
      vibrational state was assigned for ap. The microwave work was supported by
      quantum chemical calculations at the CCSD/cc-pVQZ, MP2/cc-pVTZ, and B3LYP/cc-pVTZ
      levels of theory.

PMID- 24576183
TI  - Luteal phase dynamics of follicle-stimulating and luteinizing hormones in obese
      and normal weight women.
AB  - OBJECTIVES: Female obesity is a state of relative hypogonadotrophic hypogonadism.
      The aim of this study is to examine gonadotrophin secretion and response to
      gonadotrophin-releasing hormone (GnRH) in the luteal phase of the menstrual cycle
      and to investigate the pharmacodynamics and pharmacokinetics of endogenous and
      exogenous luteinizing hormone (LH) in obese women. DESIGN: Participants underwent
      a luteal phase frequent blood sampling study. Endogenous LH pulsatility was
      observed, gonadotrophin-releasing hormone (GnRH) was given in two weight-based
      doses, and GnRH antagonist was administered followed by recombinant LH. PATIENTS:
      Regularly menstruating obese (n = 10) and normal weight (n = 10) women.
      MEASUREMENTS: Endogenous hypothalamic-pituitary function (as measured by LH
      pulsatility), pituitary sensitivity (GnRH-induced LH secretion), pharmacodynamics
      of endogenous LH and pharmacokinetics of exogenous LH were compared between the
      obese and normal weight groups. RESULTS: There were no statistically significant
      differences in endogenous LH pulsatility or pituitary responses to two weight
      based doses of GnRH between the obese and normal weight women. There were no
      differences in the pharmacodynamics of endogenous LH or the pharmacokinetics of
      exogenous LH between the groups. FSH dynamics did not differ between the groups
      throughout the study. CONCLUSIONS: The relative hypogonadotrophic hypogonadism of
      obesity cannot be explained by differences in LH and FSH luteal phase dynamics or
      differences in endogenous LH pharmacodynamics or exogenous LH pharmacokinetics.

PMID- 24576188
TI  - Oxidative stress response pathways: Fission yeast as archetype.
AB  - Schizosaccharomyces pombe is a popular model eukaryotic organism to study diverse
      aspects of mammalian biology, including responses to cellular stress triggered by
      redox imbalances within its compartments. The review considers the current
      knowledge on the signaling pathways that govern the transcriptional response of
      fission yeast cells to elevated levels of hydrogen peroxide. Particular attention
      is paid to the mechanisms that yeast cells employ to promote cell survival in
      conditions of intermediate and acute oxidative stress. The role of the
      Sty1/Spc1/Phh1 mitogen-activated protein kinase in regulating gene expression at
      multiple levels is discussed in detail. 

PMID- 24576189
TI  - Precision synthesis of subnanoparticles using dendrimers as a superatom
      synthesizer.
AB  - Classical metal-based nanomaterials come in two prominent types: a mononuclear or
      multinuclear complex chemically stabilized by organic ligands or a nanoparticle
      (also called a nanorod, nanosheet, or nanocrystal) physically stabilized by
      inorganic or polymer supports. Over the last decade, a class of superatoms that
      lies between these categories of materials has attracted attention because their
      properties are dramatically different from those typically ascribed to their
      component elements. Typically the superatoms include a specific, low number of
      metallic atoms. Because a one-atom difference can alter the properties of these
      superatoms, their synthesis must be ultraprecise, requiring one-atom resolution.
      To date, researchers have only been able to prepare monodisperse superatoms using
      gas-phase synthesis followed by purification through a flight tube. Though this
      technique provides monodisperse superatoms, it does not allow researchers to
      produce them in large quantites. Other researchers have proposed ligand-assisted
      liquid-phase synthesis as an alternative, but this technique is only useful for a
      few stable "magic number" clusters. Recently researchers have developed a new
      approach for the synthesis of superatoms that employs a novel class of molecular
      templates, which can define the number of metal ions or salts precisely. As a
      result, researchers can now synthesize nanoparticles or even subnanoparticles
      successfully. A dendrimer-type template has proven to be especially useful for
      ultraprecise control of the atomicity of the product, but it works with a full
      range of metal elements. In this Account, we highlight recent advances in the
      precise preparation of metal-assembling complexes using the dendrimer as a
      template. Next we discuss the selective assembly of subnanoparticles that utilize
      the dendrimer as a superatom synthesizer. The resulting subnanoparticles are
      almost monodisperse, and as a result, some of them exhibited distinctive
      characteristics based on their atomicity. For example, because of the quantum
      size effect, the reduction in particle size of TiO2 and other metal-oxide
      subnanoparticles led to a significant shift in the band-gap energy. In addition,
      a miniaturized platinum particle less than 1 nm in diameter showed unexpectedly
      high catalytic activity for the oxygen reduction reaction (ORR) and other related
      reactions. Of particular note, in all these examples, this substantial change in
      their properties arose out of a single-atom difference in the atomicity. These
      results suggest that next-generation subnanoparticle design could play an
      important role in new materials and offer an additional palette of physical and
      chemical properties for new applications. 

PMID- 24576187
TI  - Exploring the first delay: a qualitative study of home deliveries in Makwanpur
      district Nepal.
AB  - BACKGROUND: In many low-income countries women tend to deliver at home, and
      delays in receiving appropriate maternal care can be fatal. A contextual
      understanding of these delays is important if countries are to meet development
      targets for maternal health. We present qualitative research with women who
      delivered at home in rural Nepal, to gain a contemporary understanding of the
      context where we are testing the effectiveness of an intervention to increase
      institutional deliveries. METHODS: We purposively sampled women who had recently
      delivered at home and interviewed them to explore their reasons for home
      delivery. Interviews were recorded, transcribed and analysed using thematic
      content analysis. We used the 'delays' model discussed in the literature to frame
      our analysis. RESULTS: Usually a combination of factors prevented women from
      delivering in health institutions. Many women were aware of the benefits of
      institutional delivery yet their status in the home restricted their access to
      health facilities. Often they did not wish to bring shame on their family by
      going against their wishes, or through showing their body in a health
      institution. They often felt unable to demand the organisation of transportation
      because this may cause financial problems for their family. Some felt that
      government incentives were insufficient. Often, a lack of family support at the
      time of delivery meant that women delivered at home. Past bad experience, and
      poor quality health services, also prevented women from having an institutional
      delivery. CONCLUSIONS: Formative research is important to develop an
      understanding of local context. Sociocultural issues, perceived accessibility of
      health services, and perceived quality of care were all important barriers
      preventing institutional delivery. Targeting one factor alone may not be
      effective in increasing institutional deliveries. Our intervention encourages
      communities to develop local responses to address the factors preventing
      institutional delivery through women's groups and improved health facility
      management. We will monitor perceptions of health services over time to help us
      understand the effectiveness of the intervention.

PMID- 24576191
TI  - Surgical anatomy in obstetrics and gynaecology: the trainees' perspective.
AB  - BACKGROUND: The aim of the Royal Australian and New Zealand College of
      Obstetricians and Gynaecologists (RANZCOG) Integrated and Elective Training
      Program is to ensure trainees have both clinical and surgical competence. The
      capacity to recognise important anatomical structures underpins this aim;
      however, quantification of RANZCOG trainees' anatomical knowledge and their
      training and assessment is not available. AIM: To survey trainees at all levels
      relating to applied anatomy, training and assessment within the RANZCOG training
      program. METHODS: All accredited RANZCOG trainees were invited to participate in
      an online survey relating to anatomy knowledge, application, assessment and means
      of improving anatomical training. RESULTS: At the commencement of training, 11%
      of trainees perceived their anatomical knowledge as adequate and this increased
      to 77% by the final year of training. For final-year trainees, 78% perceived
      their anatomy knowledge as sufficient to perform a total abdominal hysterectomy
      and 87% an ovarian cystectomy or salpingectomy. Eighty-four per cent of trainees
      perceived the RANZCOG training programme as providing inadequate anatomy
      teaching. 100% of respondents supported a RANZCOG approved anatomy training
      course. LIMITATIONS: This is a survey-based study and therefore subjective.
      Consequently, accurate determination of anatomical knowledge for RANZCOG trainees
      is inexact. CONCLUSION: Trainees perceive limitations in their anatomical
      knowledge. A formalised RANZCOG anatomy course would be of value in providing
      structured education and assessment of trainees' knowledge and establishing
      whether there are improvements in surgical competencies.

PMID- 24576193
TI  - Gradient elution moving boundary electrophoresis with field-amplified continuous
      sample injection.
AB  - The integration of simple and robust device components required for the
      successful adaptation of many analytical methods to multiplexed and field
      portable devices often has negative effects on detection sensitivity, such as in
      the optical detection components in a capillary electrophoresis (CE) system. One
      of the simplest methods to improve sensitivity in the CE field is known as sample
      stacking. This method involves preparing the sample in a buffer with a different
      concentration (and conductivity) than that of the run buffer so that when an
      electric field is applied the analyte concentration is increased at the boundary
      between the two different buffer concentrations. Here, we describe a method in
      which the sample is prepared in a buffer at a lower concentration than the run
      buffer coupled with a recently described counterflow electrophoresis method,
      gradient elution moving boundary electrophoresis (GEMBE), with channel current
      detection. Because of the continuous sample introduction with GEMBE, we refer to
      the method as field-amplified continuous sample injection (FACSI). This method
      achieves a significantly greater signal enhancement than expected for sample
      stacking. For example, we achieve signal enhancement of 110* with a conductivity
      ratio of 8.21, and using the detection of arsenate in drinking water as a model
      system, we have achieved a limit of detection (LOD) improvement of approximately
      60* (LODs with and without FACSI are 200 nmol/L and 12 MUmol/L, respectively)
      with a conductivity ratio of approximately 5.93. 

PMID- 24576190
TI  - Associations between serum 25-hydroxyvitamin D concentrations and multiple health
      conditions, physical performance measures, disability, and all-cause mortality:
      the Concord Health and Ageing in Men Project.
AB  - OBJECTIVES: To explore associations between serum 25-hydroxyvitamin D (25(OH)D)
      levels and a wide range of health conditions, physical performance measures,
      disability, and mortality in a large epidemiological study to identify an optimum
      range for 25(OH)D concentrations. DESIGN: Cross-sectional study, with additional
      prospective data on falls and mortality. SETTING: Concord Health and Ageing in
      Men Project, Sydney, Australia. PARTICIPANTS: Community-dwelling men aged 70 and
      older (N = 1,659). MEASUREMENTS: Serum 25(OH)D levels, general health status,
      self-reported diseases, physical performance measures, disability (activities of
      daily living and instrumental activities of daily living) and falls. RESULTS:
      Fair, poor, and very poor health; self-reported diabetes mellitus; hyperglycemia;
      depression; muscle weakness; poor balance; and all-cause mortality were all
      associated with serum 25(OH)D levels less than 50 nmol/L, even after adjustment
      for confounding. The findings also suggest that, in older men, for a wide range
      of health conditions, physical performance measures, disability, falls, and
      mortality, the optimum range of 25(OH)D is between 50.0 and 74.9 nmol/L, with no
      additional benefit for 25(OH)D levels of 75.0 nmol/L or greater. CONCLUSION:
      Programs aimed at achieving an optimum range of serum 25(OH)D at levels between
      50.0 and 74.9 nmol/L may have overall health benefits and such levels are
      adequate for older men.

PMID- 24576192
TI  - Analysis of clinical, dermoscopic and histopathological features of primary
      melanomas of patients with metastatic disease--a retrospective study at the
      Department of Dermatology, Medical University of Graz, 2000-2010.
AB  - BACKGROUND: Incidence rates of malignant melanoma have been increasing worldwide
      and metastatic melanoma is still a significant problem despite widespread
      prevention programmes. OBJECTIVES: We made a systemic review of all metastasized
      melanoma patients treated at the Department of Dermatology, Medical University of
      Graz in the years 2000-2010 and looked at the kind of melanoma type, e.g. if it
      has been slowly growing superficial spreading melanoma (SSM) or fast growing
      nodular melanoma (NM). METHODS: Histological slides and clinical images of
      patients treated at our department between 2000 and 2010, who received
      chemotherapy because of proven metastatic disease were analysed with regard to
      growth type of their primary tumours. RESULTS: A total of 88 patients met the
      inclusion criteria. Mean age of all patients was 57 years (median 59 years, SD +/
      15 years). Of these 88 patients 51 patients (58%) (28 male patients and 23
      female patients) had SSM; mean age 58 years (median 58 years, SD +/- 14 years)
      and 37 patients (42%) (18 male patients and 19 female patients) had NM; mean age
      56 years (median 61 years, SD +/- 17 years). Mean Breslow thickness in the SSM
      group was 2.26 mm (median: 1.6 mm, SD +/- 2.11 mm). In the NM group, mean Breslow
      thickness was 4.59 mm (median: 3.50 mm, SD +/- 4.07 mm). When separated by
      gender, 46 melanomas were seen in the male group (28 SSM and 18 NM) and 42
      melanomas in the female group (23 SSM and 19 NM). CONCLUSIONS: Our results showed
      that more than half of the patients with metastatic disease had SSMs and not, as
      suspected, NMs. As SSMs are growing over a longer period to become invasive and
      potentially metastatic, there might be a chance to focus primary and secondary
      prevention programmes not only on fast growing tumours but also on slowly changes
      of tumours.

PMID- 24576194
TI  - Acute effects of whole-body vibration on running gait in marathon runners.
AB  - The aim of this study was to investigate the effects of a single bout of whole
      body vibration (WBV) on running gait. The running kinematic of sixteen male
      marathon runners was assessed on a treadmill at iso-efficiency speed after 10 min
      of WBV and SHAM (i.e. no WBV) conditions. A high-speed camera (210 Hz) was used
      for the video analysis and heart rate (HR) was also monitored. The following
      parameters were investigated: step length (SL), flight time (FT), step frequency
      (SF), contact time (CT), HR and the internal work (WINT). Full-within one-way
      analysis of variance (ANOVA) of the randomised crossover design indicated that
      when compared to SHAM conditions, WBV decreased the SL and the FT by ~4% (P <
      0.0001) and ~7.2% (P < 0.001), respectively, and increased the SF ~4% (P <
      0.0001) while the CT was not changed. This effect occurred during the first
      minute of running: the SL decreased ~3.5% (P < 0.001) and SF increased ~3.3% (P <
      0.001). During the second minute the SL decreased ~1.2% (P = 0.017) and the SF
      increased ~1.1% (P = 0.02). From the third minute onwards, there was a return to
      the pre-vibration condition. The WINT was increased by ~4% (P < 0.0001) during
      the WBV condition. Ten minutes of WBV produced a significant alteration of the
      running kinematics during the first minutes post exposure. These results provide
      insights on the effects of WBV on the central components controlling muscle
      function.

PMID- 24576195
TI  - Total synthesis of the lipid mediator PD1n-3 DPA: configurational assignments and
      anti-inflammatory and pro-resolving actions.
AB  - The polyunsaturated lipid mediator PD1n-3 DPA (5) was recently isolated from self
      resolving inflammatory exudates of 5 and human macrophages. Herein, the first
      total synthesis of PD1n-3 DPA (5) is reported in 10 steps and 9% overall yield.
      These efforts, together with NMR data of its methyl ester 6, confirmed the
      structure of 5 to be (7Z,10R,11E,13E,15Z,17S,19Z)-10,17-dihydroxydocosa
      7,11,13,15,19-pentaenoic acid. The proposed biosynthetic pathway, with the
      involvement of an epoxide intermediate, was supported by results from trapping
      experiments. In addition, LC-MS/MS data of the free acid 5, obtained from
      hydrolysis of the synthetic methyl ester 6, matched data for the endogenously
      produced biological material. The natural product PD1n-3 DPA (5) demonstrated
      potent anti-inflammatory properties together with pro-resolving actions
      stimulating human macrophage phagocytosis and efferocytosis. These results
      contribute new knowledge on the n-3 DPA structure-function of the growing numbers
      of specialized pro-resolving lipid mediators and pathways. 

PMID- 24576196
TI  - A short 2 week dose titration regimen reduces the severity of flu-like symptoms
      with initial interferon gamma-1b treatment.
AB  - OBJECTIVES: Flu-like symptoms (FLS) are commonly experienced by patients
      receiving interferon gamma-1b which may cause discontinuation or disruption of
      dosing during initial therapy or on re-initiation following a break in therapy.
      In contrast to Type I interferons, the impact of dose-titration on FLS has not
      been reported and is not a practice described or included in the approved
      prescribing information for interferon gamma-1b.The objective of this study was
      to assess the effect of a 2 week titration regimen on the severity of FLS during
      the initial 3 weeks of therapy with three times weekly subcutaneous injections of
      interferon gamma-1b. METHODS: Healthy men and women were randomized into a double
      blind, two-period, crossover study. Each study period was 3 weeks in duration and
      there was a minimum 15 day washout between treatment periods. Two treatment
      regimens were compared: No Titration dosing (full 50 mcg/m(2) subcutaneously
      [s.c.] three times weekly for 3 weeks) and Titration (15 mcg/m(2) s.c. three
      times weekly during week 1, 30 mcg/m(2) s.c. three times weekly during week 2
      followed by the full dose of 50 mcg/m(2) s.c. three times weekly during week 3).
      Subjects remained in the clinic for at least 12 hours following each injection.
      FLS was based on a composite score for fever, chills, tiredness and muscle aches
      assessed at baseline and 4, 8 and 12 hours following each injection.
      Acetaminophen was allowed at the discretion of the PI. The primary endpoint was
      the change from baseline in FLS severity at 8 hours averaged over the 3 weeks of
      treatment. Additional endpoints included FLS at 4 and 12 hours, individual flu
      like symptoms, rates of discontinuation, incidence of FLS and acetaminophen use.
      CLINICAL TRIALS REGISTRATION: NCT 01929382. RESULTS: Of the 40 subjects
      randomized, there were 15 (37.5%) discontinuations. Titration resulted in a
      significant reduction in FLS severity at 8 hours (p = 0.023) averaged over the 3
      week treatment period. The difference in 3 week FLS severity reflects differences
      during week 1 treatment, indicating an early peak in FLS severity during the No
      Titration treatment and subsequent development of tolerance. In contrast,
      titration results in near baseline severity scores throughout the treatment
      period. Similar trends were seen for 4 and 12 hour FLS severity scores. Of the
      individual FLS, difference in fever severity was most marked. Safety profiles for
      both regimens were consistent with the approved prescribing information for
      interferon gamma-1b. Study limitations included the use of healthy subjects
      rather than disease subjects, the lack of a validated assessment tool for
      evaluating FLS and the relatively high discontinuation rate. CONCLUSION: A short
      2 week, dose-titration regimen reduces FLS severity following interferon gamma-1b
      treatment initiation in normal subjects.

PMID- 24576199
TI  - Troubleshooting in LC-MS/MS method for determining endocannabinoid and
      endocannabinoid-like molecules in rat brain structures applied to assessing the
      brain endocannabinoid/endovanilloid system significance.
AB  - INTRODUCTION: In recent years, a potential participation of endocannabinoids
      (eCBs) and related endocannabinoid-like molecules, including N-acylethanolamines
      (NAEs), in the physiological and pathophysiological processes has been
      highlighted, whereas measurement of their levels still remains difficult. The aim
      of this study was to develop a bioanalytical method that would enable researchers
      to simultaneously determine quantitatively eCBs (anandamide - AEA and 2
      arachidonoylglycerol - 2-AG) and NAEs (oleoylethanolamide or oleoylethanolamine -
      OEA, palmitoylethanolamide or palmitoylethanolamine - PEA and
      linoleoylethanolamide or linoleoylethanolamine - LEA) in the rat brain. The
      analytical problems with analysis and possible solutions have been also shown.
      METHODS: The methodology for quantifying eCBs/NAEs by means of a sensitive and
      selective liquid chromatography tandem mass spectrometry (LC-MS/MS) with
      electrospray positive ionization and multiple reaction monitoring (MRM) mode was
      developed and validated. Analytical problems with analyzed compounds were
      estimated. RESULTS: Reasonably high precision and accuracy of the method were
      demonstrated in the validation process. The method is linear up to 200 ng/g for
      AEA, OEA, PEA and LEA and up to 100 MUg/g for 2-AG, while the quantification
      limit reaches 0.2 ng/g and 0.8 MUg/g, respectively. DISCUSSION: Simplicity and
      rapidity of the assay allows analyzing many samples on a routine basis. This
      article presents the new procedure applied to the analysis of brain tissues.

PMID- 24576198
TI  - Rat cavernous nerve reconstruction with CD133+ cells derived from human bone
      marrow.
AB  - INTRODUCTION: Erectile dysfunction remains a major complication after surgery of
      pelvic organs, especially after radical prostatectomy. AIM: The aim of this study
      was to assess the effect of endothelial progenitor cells on the regeneration of
      cavernous nerves in a rat injury model. METHODS: A 2 mm length of the right and
      left cavernous nerves of 8-week-old male nude rats were excised. Alginate gel
      sponge sheets supplemented with 1 * 10(4) CD133+ cells derived from human bone
      marrow were then placed over the gaps on both sides (CD group). The same
      experiments were performed on sham-operated rats (SH group), rats with only the
      nerve excision (EX group), and rats with alginate gel sheets placed on the
      injured nerves (AL group). MAIN OUTCOME MEASURES: Immunofluorescence staining and
      molecular evaluation were performed 4 days later. Functional and histological
      evaluations were performed 12 weeks later. RESULTS: The intracavernous pressure
      elicited by electrical stimulation and the neuronal nitric oxide synthase
      positive area in surrounding tissues of the prostate was significantly greater in
      the CD group. Immunofluorescence microscopy showed that CD133+ cells were
      assimilated as vascular endothelial cells, and the real-time polymerase chain
      reaction showed upregulation of nerve growth factor and vascular endothelial
      growth factor in the alginate gel sponge sheets of the CD group. CONCLUSIONS:
      Transplantation of CD133+ cells accelerated the functional and histological
      recovery in this cavernous nerve injury model, and the recovery mechanism is
      thought to be angiogenesis and upregulation of growth factors. CD133+ cells could
      be an optional treatment for cavernous nerve injury after prostatectomy in
      clinical settings.

PMID- 24576200
TI  - The effects of read length, quality and quantity on microsatellite discovery and
      primer development: from Illumina to PacBio.
AB  - The advent of next-generation sequencing (NGS) technologies has transformed the
      way microsatellites are isolated for ecological and evolutionary investigations.
      Recent attempts to employ NGS for microsatellite discovery have used the 454,
      Illumina, and Ion Torrent platforms, but other methods including single-molecule
      real-time DNA sequencing (Pacific Biosciences or PacBio) remain viable
      alternatives. We outline a workflow from sequence quality control to
      microsatellite marker validation in three plant species using PacBio circular
      consensus sequencing (CCS). We then evaluate the performance of PacBio CCS in
      comparison with other NGS platforms for microsatellite isolation, through
      simulations that focus on variations in read length, read quantity and sequencing
      error rate. Although quality control of CCS reads reduced microsatellite yield by
      around 50%, hundreds of microsatellite loci that are expected to have improved
      conversion efficiency to functional markers were retrieved for each species. The
      simulations quantitatively validate the advantages of long reads and emphasize
      the detrimental effects of sequencing errors on NGS-enabled microsatellite
      development. In view of the continuing improvement in read length on NGS
      platforms, sequence quality and the corresponding strategies of quality control
      will become the primary factors to consider for effective microsatellite
      isolation. Among current options, PacBio CCS may be optimal for rapid, small
      scale microsatellite development due to its flexibility in scaling sequencing
      effort, while platforms such as Illumina MiSeq will provide cost-efficient
      solutions for multispecies microsatellite projects. 

PMID- 24576201
TI  - Clinical, biochemical and imaging characteristics of Cushing's macroadenomas and
      their long-term treatment outcome.
AB  - OBJECTIVE: Cushing's macroadenoma as a cause of Cushing's disease is less common
      than microadenoma. The data on nature and behaviour of Cushing's macroadenoma are
      limited to a few case series. We studied clinical, biochemical and imaging
      characteristics of macroadenoma and their long-term treatment outcomes. METHOD:
      Retrospective analysis of 40 patients with macroadenoma managed at our centre
      from 1997 to 2013. RESULTS: Of 40 patients, there were 15 (37.5%) males and 25
      (62.5%) females. Mean age at presentation was 26.7 +/- 9.3 years. Visual field
      defects and/or cranial nerve palsies were found in 15 cases at presentation. Mean
      maximum tumour dimension was 20.83 +/- 10.74 mm, and parasellar extension was
      seen in 25 (62.5%) patients. Plasma ACTH/maximum tumour dimension and 8 am serum
      cortisol/maximum tumour dimension decreased with increasing tumour size. Sixteen
      patients (40%) had remission (4: immediate, 12: delayed) after first
      transsphenoidal surgery (TSS). Larger tumour size and parasellar extension were
      predictors of failure to achieve remission. Four patients relapsed; noticeably
      all of them had delayed remission. Among the persistent and relapsed cases,
      second TSS was successful in two of eight patients, whereas 11 of 16 patients
      achieved remission after a mean duration of 12.14 +/- 8.41 months
      postradiotherapy. CONCLUSION: Younger age at presentation and larger tumour size
      compared with previous series were distinctive features of our series. Large
      tumour size and parasellar extension were negative predictors of surgical
      remission. Delayed remission was seen in significant proportion of patients, but
      one-third later relapsed. Radiotherapy was an effective second-line treatment
      modality.

PMID- 24576202
TI  - Effect of systematic local infiltration analgesia on postoperative pain in
      vaginal hysterectomy: a randomized, placebo-controlled trial.
AB  - OBJECTIVE: To assess the effect of systematic local infiltration analgesia on
      postoperative pain in vaginal hysterectomy, and describe the technique in detail.
      DESIGN: A randomized, double-blind, placebo-controlled study following the
      CONSORT criteria. SETTING: A university hospital. PATIENTS: Thirty-seven patients
      undergoing vaginal hysterectomy. METHODS: Patients received high-volume (50 mL)
      ropivacaine 0.50% (n = 20) or saline (n = 17) infiltration using a systematic
      technique ensuring uniform delivery to all tissues incised, handled or
      instrumented during the procedure. MAIN OUTCOME MEASURES: Pain, nausea, vomiting
      and opioid requirements were assessed for 32 h as well as time spent in the post
      anesthesia care unit and time to first mobilization. RESULTS: Pain at rest was
      significantly reduced after one, four and eight hours in the ropivacaine group (p
      <= 0.001-0.01). Pain during coughing was significantly reduced after one and four
      hours (p <= 0.001 and p <= 0.003), and pain during movement was significantly
      reduced after four hours (p <= 0.02). Opioid requirements and time spent in the
      post-anesthesia care unit were significantly reduced in the ropivacaine group (p
      < 0.001 and p < 0.001, respectively), as well as the time to first mobilization
      (p < 0.001). CONCLUSION: Intra-operative systematic local infiltration analgesia
      reduces postoperative pain in patients undergoing vaginal hysterectomy,
      facilities mobilization and improves early recovery.

PMID- 24576203
TI  - Household members of persons with Alzheimer's disease: health conditions,
      healthcare resource use, and healthcare costs.
AB  - OBJECTIVES: To compare medical condition burden, healthcare resource use, and
      healthcare costs of household members (HHMs) of individuals diagnosed with
      Alzheimer's disease (AD) with those of HHMs of matched individuals without AD.
      DESIGN: Retrospective cohort study based on administrative claims data collected
      between January 1, 2007, and December 31, 2011. SETTING: Medicare Advantage
      Prescription Drug (MAPD) plan. PARTICIPANTS: MAPD plan members with a diagnosis
      of AD (International Classification of Disease Ninth Revision, Clinical
      Modification, code 331.0) were selected and linked to a HHM to form patient-HHM
      dyads. AD dyads were matched to non-AD dyads. MEASUREMENTS: Health-related
      endpoints, including medical condition burden, healthcare resource use, and
      direct healthcare costs, were measured during 36 months of continuous health plan
      enrollment. RESULTS: Individuals with AD (n = 1,861) were linked to HHMs (n =
      1,861), and these AD dyads were matched to 1,861 non-AD patient-HHM dyads. AD
      HHMs had greater medical condition burden scores than non-AD HHMs, with mood
      disorders, anxiety disorders, insomnia, substance abuse or dependence,
      cardiovascular disease, and rheumatoid arthritis being more prevalent in AD HHMs.
      Emergency department and outpatient service use were more common in AD HHMs than
      in non-AD HHMs, and AD HHMs had greater healthcare costs. CONCLUSION: HHMs of
      individuals diagnosed with AD demonstrated greater medical condition burden,
      healthcare resource use, and direct healthcare costs than non-AD HHMs. These
      findings demonstrate the significant clinical and financial impact of AD on HHMs
      of individuals with AD.

PMID- 24576204
TI  - Reversible assembly of beta-sheet nanocrystals within caddisfly silk.
AB  - Nuclear magnetic resonance (NMR) and X-ray diffraction (XRD) experiments reveal
      the structural importance of divalent cation-phosphate complexes in the formation
      of beta-sheet nanocrystals from phosphorylated serine-rich regions within aquatic
      silk from caddisfly larvae of the species Hesperophyla consimilis. Wide angle XRD
      data on native caddisfly silk show that the silk contains a significant
      crystalline component with a repetitive orthorhombic unit cell aligned along the
      fiber axis with dimensions of 5.9 A * 23.2 A * 17.3 A. These nanocrystalline
      domains depend on multivalent cations, which can be removed through chelation
      with ethylenediaminetetraacetic acid (EDTA). A comparison of wide angle X-ray
      diffraction data before and after EDTA treatment reveals that the integrated peak
      area of reflections corresponding to the nanocrystalline regions decreases by 15
      25% while that of the amorphous background reflections increases by 20%,
      indicating a partial loss of crystallinity. (31)P solid-state NMR data on native
      caddisfly silk also show that the phosphorylated serine-rich motifs transform
      from a rigid environment to one that is highly mobile and water-solvated after
      treatment with EDTA. The removal of divalent cations through exchange and
      chelation has therefore caused a collapse of the beta-sheet structure. However,
      NMR results show that the rigid phosphorus environment is mostly recovered after
      the silk is re-treated with calcium. The (31)P spin-lattice (T1) relaxation times
      were measured at 7.6 +/- 3.1 and 1 +/- 0.5 s for this calcium-recovered sample
      and the native silk sample, respectively. The shorter (31)P T1 relaxation times
      measured for the native silk sample are attributed to the presence of
      paramagnetic iron that is stripped away during EDTA chelation treatment and
      replaced with diamagnetic calcium. 

PMID- 24576206
TI  - Measurement of in vivo drug load distribution of cysteine-linked antibody-drug
      conjugates using microscale liquid chromatography mass spectrometry.
AB  - Analysis of samples containing intact antibody-drug conjugates (ADC) using mass
      spectrometry provides a direct measurement of the drug-load distribution. Once
      dosed, the drug load distribution changes due to a combination of biological and
      chemical factors. Liquid chromatography-mass spectrometry (LC-MS) methods to
      measure the in vivo drug load distribution have been established for ADCs
      containing native disulfide bonds (lysine-linked or cysteine-linked). However,
      because of an IgG reduction step in conjugation processes, using LC-MS to analyze
      intact cysteine-linked ADCs requires native conditions, thus limiting
      sensitivity. While this limitation has been overcome at the analytical scale, to
      date, these methods have not been translated to a smaller scale that is required
      for animal or clinical doses/sampling. In this manuscript, we describe the
      development of ADC specific affinity capture reagents for processing in vivo
      samples and optimization of native LC-MS methods at a microscale. These methods
      are then used to detect the changing drug load distribution over time from a set
      of in vivo samples, representing to our knowledge the first native mass spectra
      of cysteine-linked ADCs from an in vivo source. 

PMID- 24576205
TI  - Adverse birth outcomes among deliveries at Gondar University Hospital, Northwest
      Ethiopia.
AB  - BACKGROUND: Adverse birth outcomes are major public health problems in developing
      countries. Data, though scarce in developing countries including Ethiopia, on
      adverse birth outcomes and the risk factors are important for planning maternal
      and child health care services. Hence, this study aimed to determine the
      prevalence and associated factors of adverse birth outcomes among deliveries at
      Gondar University Hospital, Northwest Ethiopia. METHODS: Institution based cross
      sectional study was conducted in February 2013 at Gondar University Hospital.
      Data were collected by face-to-face interview of 490 women after verbal informed
      consent using a pretested and structured questionnaire. Gestational age was
      determined based on the last normal menstrual period. Birth weight was measured
      following standards. Multiple logistic regressions were fitted and odds ratios
      with their 95% confidence interval were computed to identify associated factors.
      RESULTS: The mean age of women was 26.2 (+/-5.2 SD) years. HIV infection among
      laboring women was 4.8%. About 23% of women had adverse birth outcomes (14.3%
      preterm, 11.2% low birth weight and 7.1% still births). Women having history of
      either preterm delivery or small baby (AOR: 3.1, 95% CI 1.1- 8.4) were more
      likely to have preterm births. Similarly, history of delivering preterm or small
      baby (AOR: 8.4, 95% CI 2.4- 29.4), preterm birth (AOR: 5.5, 95% CI 2.6- 11.6) and
      hypertension (AOR: 5.8, 95% CI 1.8- 19.6) were associated factors with low birth
      weight. Ante partum haemorrhage (AOR: 8.43, 95% CI 1.28- 55.34), hypertension
      (AOR: 9.5, 95% CI 2.1-44.3), history of perinatal death (AOR: 13.9, 95% CI 3.3-
      58.5) and lack of antenatal care follow up (AOR: 9.7, 95% CI 2.7 - 35.8) were
      significantly associated with still birth. CONCLUSIONS: Prevalence of adverse
      birth outcomes (still birth, preterm birth and low birth weight) were high and
      still a major public health problem in the area. Histories of perinatal death,
      delivering preterm or small baby, ante partum hemorrhage, lack of ante natal care
      follow up and hypertension were associated factors with adverse birth outcomes.
      Thus, further enhancements of ante natal and maternal care and early screening
      for hypertension are recommended.

PMID- 24576207
TI  - A comparison of two different mesh kit systems for anterior compartment prolapse
      repair.
AB  - BACKGROUND AND AIM: Mesh reinforcement is considered an effective method for
      anterior compartment prolapse repair. Two common methods of mesh reinforcement
      involve either transobturator fixation (eg PerigeeTM) or lateral and apical
      anchoring (eg Anterior ElevateTM). The aim of this study was to assess subjective
      and objective outcomes after Anterior Elevate and Perigee mesh kit surgery.
      MATERIALS AND METHODS: This was a surgical audit of patients after anterior
      colporrhaphy (AC) with mesh reinforcement, undertaken at three tertiary
      urogynaecological centres. All patients were assessed for prolapse recurrence,
      which was defined as either (i) symptoms of prolapse (vaginal lump/dragging),
      (ii) ICS POPQ >= Stage 2, or (iii) bladder descent >=10 mm below the symphysis
      pubis on transperineal ultrasound. Mesh co-ordinates and organ descent on
      Valsalva were determined relative to the inferior symphyseal margin. RESULTS: Two
      hundred and twenty-nine patients with anterior compartment mesh (138 Perigee, 91
      Elevate) were assessed at a median follow-up of 1.09 years (IQR 0.65-2.01). On
      assessment, 24% (n = 55) had symptoms of prolapse recurrence, 46% (n = 106) had a
      clinical recurrence, and 41% (n = 95) a recurrent cystocele sonographically. All
      objective results favoured the Perigee group. The superiority of the Perigee kit
      remained highly significant (P < 0.0001 for all clinical and ultrasound measures
      of prolapse recurrence) on multivariate analysis. CONCLUSIONS: This retrospective
      analysis suggests that apical anchoring such as Anterior Elevate mesh system does
      not necessarily confer an advantage over the original transobturator mesh
      fixation technique for anterior compartment reconstruction.

PMID- 24576208
TI  - Canine and feline blood transfusions: controversies and recent advances in
      administration practices.
AB  - OBJECTIVES: To discuss and review blood transfusion practices in dogs and cats
      including collection and storage of blood and administration of products. To
      report new developments, controversial practices, less conventional blood product
      administration techniques and where applicable, describe the relevance to
      anaesthetists and anaesthesia. DATABASES USED: PubMed and Google Scholar using
      dog, cat, blood transfusion, packed red blood cells and whole blood as keywords.
      CONCLUSIONS: Blood transfusions improve oxygen carrying capacity and the clinical
      signs of anaemia. However there are numerous potential risks and complications
      possible with transfusions, which may outweigh their benefits. Storage of blood
      products has improved considerably over time but whilst extended storage times
      may improve their availability, a phenomenon known as the storage lesion has been
      identified which affects erythrocyte viability and survival. Leukoreduction
      involves removing leukocytes and platelets thereby preventing their release of
      cytokines and bioactive compounds which also contribute to storage lesions and
      certain transfusion reactions. Newer transfusion techniques are being explored
      such as cell salvage in surgical patients and subsequent autologous transfusion.
      Xenotransfusions, using blood and blood products between different species,
      provide an alternative to conventional blood products.

PMID- 24576209
TI  - Early predictors of middle school fraction knowledge.
AB  - Recent findings that earlier fraction knowledge predicts later mathematics
      achievement raise the question of what predicts later fraction knowledge.
      Analyses of longitudinal data indicated that whole number magnitude knowledge in
      first grade predicted knowledge of fraction magnitudes in middle school,
      controlling for whole number arithmetic proficiency, domain general cognitive
      abilities, parental income and education, race, and gender. Similarly, knowledge
      of whole number arithmetic in first grade predicted knowledge of fraction
      arithmetic in middle school, controlling for whole number magnitude knowledge in
      first grade and the other control variables. In contrast, neither type of early
      whole number knowledge uniquely predicted middle school reading achievement. We
      discuss the implications of these findings for theories of numerical development
      and for improving mathematics learning. 

PMID- 24576210
TI  - Guanacastane diterpenoids from the plant endophytic fungus Cercospora sp.
AB  - Cercosporenes A-F (1-6, respectively), six new guanacastane diterpenes, including
      a homodimer (5) and a heterodimer (6), were isolated from the crude extract of
      the fungus Cercospora sp., endophytic to the medicinal plant Fallopia japonica.
      The structures of 1-6 were elucidated by nuclear magnetic resonance experiments,
      and 4 and 5 were further confirmed by X-ray crystallography. The absolute
      configuration of 1 and 3 was assigned by electronic circular dichroism
      calculations, whereas that of 6 was deduced by the application of the circular
      dichroism exciton chirality method. In addition to its cytotoxicity against a
      panel of five human tumor cell lines, HeLa, A549, MCF-7, HCT116, and T24,
      heterodimer 6 also induced autophagy in HCT116 cells. 

PMID- 24576211
TI  - Relation of the unipolar low-voltage penumbra surrounding the endocardial low
      voltage scar to ventricular tachycardia circuit sites and ablation outcomes in
      ischemic cardiomyopathy.
AB  - INTRODUCTION: Magnetic resonance (MR)-imaging has shown that infarct scars
      causing ventricular tachycardia (VT) can extend deep to and beyond bipolar low
      voltage areas (LVAs) and may be a source of ablation failure. We hypothesized
      that the size of the unipolar LVA "penumbra" beyond the overlying bipolar scar
      may predict outcome of endocardial VT ablation. METHODS: Twenty consecutive
      patients with ischemic cardiomyopathy who underwent endocardial VT ablation were
      retrospectively reviewed. Bipolar (30-500 Hz) LVA defined as <1.5 mV and unipolar
      (0.5-500 Hz) LVA defined as <8.3 mV were reviewed on an electroanatomic mapping
      system. VT isthmus sites were identified from entrainment mapping, VT termination
      by ablation, or pace-mapping with abolition of VT inducibility by ablation.
      RESULTS: All bipolar LVAs (70.5 +/- 20 cm(2) ) had unipolar LVAs that surrounded
      the bipolar LVA (147 +/- 47 cm(2) ). Only 58% of the induced VTs could be mapped
      and ablated. During a 3-month follow-up 8/20 patients had VT recurrence. The size
      of the LVA penumbra was not different for those with (88 +/- 47 cm(2) ) versus
      without (69 +/- 35 cm(2) ) recurrences. However, all (8/8) of the group that
      recurred had isthmus/exits in the bipolar LVA border compared to only 3/12 that
      did not recur (100% vs. 25%; P < 0.05). Furthermore, 5/8 patients who recurred
      harbored VT isthmuses in the unipolar LVA penumbra than 1/12 who did not recur
      (63% vs. 8%; P = 0.01). CONCLUSION: In ischemic cardiomyoapthy, unipolar LVA
      penumbra of varying size surrounds endocardial bipolar LVA, indicating
      intramural/epicardial scar. Although the size of this area did not predict early
      recurrence after endocardial ablation, frequent recurrences after VT ablation at
      scar periphery suggests deeper substrate toward the infarct border.

PMID- 24576212
TI  - Acute neuromuscular and metabolic responses to combined strength and endurance
      loadings: the "order effect" in recreationally endurance trained runners.
AB  - The study examined the acute neuromuscular and metabolic responses and recovery
      (24 and 48 h) to combined strength and endurance sessions (SEs). Recreationally
      endurance trained men (n = 12) and women (n = 10) performed: endurance running
      followed immediately by a strength loading (combined endurance and strength
      session (ES)) and the reverse order (SE). Maximal strength (MVC), countermovement
      jump height (CMJ), and creatine kinase activity were measured pre-, mid-, post
      loading and at 24 and 48 h of recovery. MVC and CMJ were decreased (P < 0.05) at
      post-ES and SE sessions in men. Only MVC decreased in ES and SE women (P < 0.05).
      During recovery, no order differences in MVC were observed between sessions in
      men, but MVC and CMJ remained decreased. During recovery in women, a delayed
      decrease in CMJ was observed in ES but not in SE (P < 0.01), while MVC returned
      to baseline at 24 h. Creatine kinase increased (P < 0.05) during both ES and SE
      and peaked in all groups at 24 h. The present combined ES and SE sessions induced
      greater neuromuscular fatigue at post in men than in women. The delayed fatigue
      response in ES women may be an order effect related to muscle damage.

PMID- 24576213
TI  - Piezoelectric hydrogen bonding: computational screening for a design rationale.
AB  - Organic piezoelectric materials are promising targets in applications such as
      energy harvesting or mechanical sensors and actuators. In a recent paper
      (Werling, K. A.; et al. J. Phys. Chem. Lett. 2013, 4, 1365-1370), we have shown
      that hydrogen bonding gives rise to a significant piezoelectric response. In this
      article, we aim to find organic hydrogen bonded systems with increased piezo
      response by investigating different hydrogen bonding motifs and by tailoring the
      hydrogen bond strength via functionalization. The largest piezo-coefficient of 23
      pm/V is found for the nitrobenzene-aniline dimer. We develop a simple, yet
      surprisingly accurate rationale to predict piezo-coefficients based on the zero
      field compliance matrix and dipole derivatives. This rationale increases the
      speed of first-principles piezo-coefficient calculations by an order of
      magnitude. At the same time, it suggests how to understand and further increase
      the piezo-response. Our rationale also explains the remarkably large piezo
      response of 150 pm/V and more for another class of systems, the "molecular
      springs" (Marvin, C.; et al. J. Phys. Chem. C 2013, 117, 16783-16790.).

PMID- 24576215
TI  - Transferring MBE-grown topological insulator films to arbitrary substrates and
      metal-insulator transition via Dirac gap.
AB  - Mechanical exfoliation of bulk crystals has been widely used to obtain thin
      topological insulator (TI) flakes for device fabrication. However, such a process
      produces only microsized flakes that are highly irregular in shape and thickness.
      In this work, we developed a process to transfer the entire area of TI Bi2Se3
      thin films grown epitaxially on Al2O3 and SiO2 to arbitrary substrates,
      maintaining their pristine morphology and crystallinity. Transport measurements
      show that these transferred films have lower carrier concentrations and
      comparable or higher mobilities than before the transfer. Furthermore, using this
      process we demonstrated a clear metal-insulator transition in an ultrathin Bi2Se3
      film by gate-tuning its Fermi level into the hybridization gap formed at the
      Dirac point. The ability to transfer large area TI films to any substrate will
      facilitate fabrication of TI heterostructure devices, which will help explore
      exotic phenomena such as Majorana fermions and topological magnetoelectricity. 

PMID- 24576214
TI  - NADH-dependent glutamate synthase plays a crucial role in assimilating ammonium
      in the Arabidopsis root.
AB  - Plant roots under nitrogen deficient conditions with access to both ammonium and
      nitrate ions, will take up ammonium first. This preference for ammonium rather
      than nitrate emphasizes the importance of ammonium assimilation machinery in
      roots. Glutamine synthetase (GS) and glutamate synthase (GOGAT) catalyze the
      conversion of ammonium and 2-oxoglutarate to glutamine and glutamate. Higher
      plants have two GOGAT species, ferredoxin-dependent glutamate synthase (Fd-GOGAT)
      and nicotinamide adenine dinucleotide (NADH)-GOGAT. While Fd-GOGAT participates
      in the assimilation of ammonium, which is derived from photorespiration in
      leaves, NADH-GOGAT is highly expressed in roots and its importance needs to be
      elucidated. While ammonium as a minor nitrogen form in most soils is directly
      taken up, nitrate as the major nitrogen source needs to be converted to ammonium
      prior to uptake. The aim of this study was to investigate and quantify the
      contribution of NADH-GOGAT to the ammonium assimilation in Arabidopsis
      (Arabidopsis thaliana Columbia) roots. Quantitative real-time polymerase chain
      reaction (PCR) and protein gel blot analysis showed an accumulation of NADH-GOGAT
      in response to ammonium supplied to the roots. In addition the localization of
      NADH-GOGAT and Fd-GOGAT did not fully overlap. Promoter-beta-glucuronidase (GUS)
      fusion analysis and immunohistochemistry showed that NADH-GOGAT was highly
      accumulated in non-green tissue like vascular bundles, shoot apical meristem,
      pollen, stigma and roots. Reverse genetic approaches suggested a reduction in
      glutamate production and biomass accumulation in NADH-GOGAT transfer DNA (T-DNA)
      insertion lines under normal CO2 condition. The data emphasize the importance of
      NADH-GOGAT in the ammonium assimilation in Arabidopsis roots. 

PMID- 24576216
TI  - Body mass index, blood pressure, and glucose and lipid metabolism among permanent
      and fixed-term workers in the manufacturing industry: a cross-sectional study.
AB  - BACKGROUND: Temporary employment, a precarious form of employment, is recognized
      as social determinant of poor health. However, evidence supporting precarious
      employment as a risk factor for health is mainly obtained from subjective data.
      Studies using objective clinical measurement data in the assessment of health
      status are limited. This study compared body mass index (BMI), lipid and glucose
      metabolism, and health-related lifestyle factors between permanent workers and
      fixed-term workers employed in the manufacturing industry. METHODS: Data of 1,701
      male manufacturing industry workers <50 years old in Japan were collected and
      analyzed. Anthropometric data were BMI, calculated using measured height and
      weight of study participants, and blood pressure. For lipid metabolism, low
      density lipoprotein cholesterol, high-density lipoprotein cholesterol, and
      triglyceride levels were determined. For glucose metabolism, fasting plasma
      glucose and hemoglobin A1c (HbA1c) levels were measured. Multiple regression
      analysis adjusted for age and lifestyle factors was performed. RESULTS: BMI was
      significantly higher in permanent workers (22.9 kg/m2) compared with fixed-term
      workers (22.4 kg/m2). The leaner population (BMI < 18.5) was greater among fixed
      term workers (8.3%) compared with permanent workers (4.0%), whereas the
      overweight population (BMI >= 25.0) was greater among permanent workers (21.4%)
      compared with fixed-term workers (18.1%). Although fixed-term workers tended not
      to be overweight, regression analysis adjusted for age and lifestyle factors
      suggested that fixed-term employment was significantly associated with higher
      blood pressure (systolic beta = 2.120, diastolic beta = 2.793), triglyceride
      (beta = 11.147), fasting blood glucose (beta = 2.218), and HbA1c (beta = 0.107)
      compared with permanent workers (all p < 0.01). CONCLUSIONS: Fixed-term workers
      showed more health risks, such as poorer blood pressure and lipid and glucose
      metabolism, even when adjusted for age and lifestyle variables, although BMI of
      fixed-term workers were lower than permanent workers. Precarious work might
      contribute to a deteriorating health status even among less overweight
      populations.

PMID- 24576219
TI  - Newly identified phenotypes in a FIP1L1/PDGFRA-associated paediatric HES patient:
      thrombocytosis, mHPA, young stroke and blindness.

PMID- 24576218
TI  - Detection of microbial agents in ticks collected from migratory birds in central
      Italy.
AB  - Tick species characterization and molecular studies were performed within
      ornithological surveys conducted during 2010 and 2011 in the Lazio Region of
      central Italy. A total of 137 ticks were collected from 41 migratory birds
      belonging to 17 species (four partial migrants and 13 long-distance migrants).
      Most ticks were nymphs, with a predominance of Hyalomma marginatum marginatum and
      H. m. rufipes, and a small portion of Ixodes and Amblyomma species. All tick
      species analyzed were infected, and the molecular pathogen recognition revealed
      the presence of Rickettsia aeschlimannii, Rickettsia africae, Erlichia spp.,
      Coxiella burnetii, Borrelia burgdorferi sensu lato group, and Babesia microti,
      whereas no genomic DNA of Bartonella spp. or Francisella tularensis was detected.
      The results of the survey show that H. marginatum ticks appear to be a vector of
      microbial agents that may affect human and animal health and that migratory birds
      may be an important carrier of these ticks. Additional studies are needed to
      better investigate the role of migratory birds in the epidemiology of these
      pathogens.

PMID- 24576220
TI  - Protective effects of Eugenia jambolana extract versus N-acetyl cysteine against
      cisplatin-induced damage in rat testis.
AB  - To assess the protective effects of Eugenia jambolana extract (EJE) or N-acetyl
      cysteine (NAC) on testis, cisplatin (CIS, 5 mg kg(-1) bw, single dose) was
      administered either alone or along with EJE (25 mg kg(-1) bw, alternate day) or
      NAC (150 mg kg(-1) bw, Day 1 and 4) for 7 days. Significant alterations in serum
      LH, FSH and testosterone were observed in CIS group which were effectively
      modulated by EJE or NAC supplementation. Upregulation of 3beta-HSD gene indicated
      the rise in functional Leydig cells. This was further confirmed from the
      identical improvement in hCG-stimulated testosterone production in isolated
      Leydig cells. Reduction in oxidative stress was associated with restoration of
      total antioxidant capacity and glutathione levels, and activation of antioxidant
      enzymes, SOD, catalase, glutathione s-transferase (GST) and glutathione reductase
      (GR). CIS-induced apoptosis of germ and Leydig cells was contained by both NAC
      and EJE intervention by effective modulation of apoptotic markers in the
      extrinsic, intrinsic and other pathways of metazoan apoptosis. Taken together,
      the study findings establish the potential of EJE as a therapeutically better
      antioxidant than NAC for use in curtailing the adverse effects of anticancer
      drugs on testicular function.

PMID- 24576221
TI  - Clinical significance of atypical glandular cells in the Bethesda system 2001: a
      comparison with the histopathological diagnosis of surgically resected specimens.
AB  - Forty-one patients diagnosed with atypical glangular cells (AGC) underwent
      surgery, and the histopathological diagnosis results for the resected specimens
      and the clinical features were analyzed. Out of 41 patients, final pathological
      diagnosis was endometrial cancer in 13 patients, cervical adenocarcinoma in 8,
      AIS in 7, CIN3 in 6, others in 2, and no lesions in 5. In comparison with
      previous reports, malignant or premalignant lesions were detected more frequently
      in patients with AGC who underwent surgery. We believe that conization or
      hysterectomy aimed at diagnosis and treatment, as well as endometrial
      histodiagnosis, should be carried out aggressively in patients with AGC. 

PMID- 24576222
TI  - Hypoxia-inducible factor-1alpha C1772T polymorphism and cancer risk: a meta
      analysis including 18,334 subjects.
AB  - Studies on HIF 1alpha C1772T (P582S) polymorphism revealed a genetic
      susceptibility to malignant tumors, however, the results were conflicting. We
      conducted a meta-analysis utilizing 29 eligible case-control studies to analyze
      the data concerning the association between the HIF-1alpha C1772T polymorphism
      and cancer risks. There was statistical association between the HIF-1alpha CT/TT
      genotype and cancer risk (OR = 1.28, 95% CI = 1.06-1.54, P(heterogeneity) <
      .00001). The stability of these observations was confirmed by a one-way
      sensitivity analysis. Our findings suggested that CT/TT genotype was associated
      with increased risks of prostate cancer. Besides, the HIF-1alpha C1772T
      polymorphism most likely contributes to susceptibility to malignant tumors,
      especially in American population.

PMID- 24576224
TI  - Live birth after frozen-thawed oocytes matured in vitro in a PCOS patient: a
      model for improving implantation rates in IVM cycles and objectively assessing
      the real potential of development of frozen oocytes matured in vitro.
AB  - Over the past 20 years, in vitro maturation (IVM) of oocytes has emerged in the
      strategy of infertility treatment, with the main indication being in patients
      suffering from polycystic ovarian syndrome (PCOS). More recently, IVM has been
      proposed as an option for fertility preservation in women having to undergo
      gonadotoxic treatments. However, despite the increasing application of IVM, the
      potential of development of in vitro matured oocytes after thawing remains ill
      established and few pregnancies have been reported so far. We report herein a
      case of live birth after frozen-thawed oocytes matured in vitro and embryo
      transfer during an artificial cycle in a 29-year-old patient with primary
      infertility due to PCOS. The present case demonstrates that the transfer of
      frozen-thawed IVM oocytes during an artificial cycle in PCOS patients is feasible
      and leads to pregnancy and live birth. This strategy may also be an interesting
      option to objectively assess the developmental potential of these oocytes after
      freezing and thawing, which is a major concern for physicians who include the IVM
      approach in their fertility preservation program.

PMID- 24576223
TI  - Factors associated with severe maternal morbidity and near miss in the Sao
      Francisco Valley, Brazil: a retrospective, cohort study.
AB  - BACKGROUND: Maternal mortality remains a major public health issue worldwide,
      with persistent high rates prevailing principally in underdeveloped countries.
      The objective of this study was to determine the risk factors for severe maternal
      morbidity and near miss (SMM/NM) in pregnant and postpartum women at the
      maternity ward of the Dom Malan Hospital, Petrolina, in northeastern Brazil.
      METHODS: A retrospective, cohort study was conducted to evaluate the
      sociodemographic and obstetric characteristics of the women. Patients who
      remained hospitalized at the end of the study period were excluded. Risk ratios
      (RR) and their respective 95% confidence intervals (95% CI) were calculated as a
      measure of relative risk. Hierarchical multiple logistic regression was also
      performed. Two-tailed p-values were used for all the tests and the significance
      level adopted was 5%. RESULTS: A total of 2,291 pregnant or postpartum women
      receiving care between May and August, 2011 were included. The frequencies of
      severe maternal morbidity and near miss were 17.5% and 1.0%, respectively.
      Following multivariate analysis, the factors that remained significantly
      associated with an increased risk of SMM/NM were a Cesarean section in the
      current pregnancy (OR: 2.6; 95% CI: 2.0 - 3.3), clinical comorbidities (OR: 3.4;
      95% CI: 2.5 - 4.4), having attended fewer than six prenatal visits (OR: 1.1; 95%
      CI: 1.01 - 1.69) and the presence of the third delay (i.e. delay in receiving
      care at the health facility) (OR: 13.3; 95% CI: 6.7 - 26.4). CONCLUSIONS: The
      risk of SMM/NM was greater in women who had been submitted to a Cesarean section
      in the current pregnancy, in the presence of clinical comorbidities, fewer
      prenatal visits and when the third delay was present. All these factors could be
      minimized by initiating a broad debate on healthcare policies, introducing
      preventive measures and improving the training of the professionals and services
      providing obstetric care.

PMID- 24576225
TI  - Correlation of visfatin levels and lipoprotein lipid profiles in women with
      polycystic ovary syndrome undergoing ovarian stimulation.
AB  - The aim of this study was to determine serum and follicular fluid (FF) visfatin
      levels in age and weight-matched women with polycystic ovary syndrome (PCOS) and
      normally ovulating subjects undergoing controlled ovarian stimulation and
      correlate them with their lipid and lipoprotein levels. We included 80 PCOS women
      (40 lean and 40 overweight) and 80 age- and weight-matched controls, enrolled in
      the IVF program. In PCOS women, we determined significantly increased serum and
      FF visfatin as well as serum levels of total cholesterol, low-density lipoprotein
      (LDL) cholesterol, triglycerides, apolipoprotein B, lipoprotein(a) and
      homocysteine, while high-density lipoprotein cholesterol and apolipoprotein A1
      were significantly lower compared to controls. Serum visfatin levels positively
      correlated with total cholesterol, LDL cholesterol, triglycerides, lipoprotein(a)
      and homocysteine levels and negatively with apolipoprotein A1. FF visfatin levels
      positively correlated with triglycerides and homocysteine and negatively with
      apolipoprotein A1. Dyslipidemia is common in reproductive age women with PCOS
      exposing them to risk for cardiovascular diseases. However, the detailed role of
      visfatin on lipoprotein lipid profile awaits further clarification through future
      investigation.

PMID- 24576227
TI  - From cascaded catalytic nucleic acids to enzyme-DNA nanostructures: controlling
      reactivity, sensing, logic operations, and assembly of complex structures.

PMID- 24576229
TI  - A familiar story.

PMID- 24576228
TI  - Pregnancy after definitive treatment for Graves' disease--does treatment choice
      influence outcome?
AB  - BACKGROUND: Women requiring thyroid hormone replacement after definitive therapy
      (surgery or radioiodine) for Graves' disease who later conceive require an early
      increase in levothyroxine dose and monitoring of thyroid hormone levels
      throughout pregnancy. In addition, as TSH receptor antibodies (TRAb) can cross
      the placenta and affect the fetus, measurement of these antibodies during
      pregnancy is recommended. AIM: To review the management of pregnancies following
      definitive treatment for Graves' disease in order to assess the rates of maternal
      hypothyroidism and TRAb measurement. MATERIALS AND METHODS: Retrospective chart
      review of women who had undergone definitive treatment for Graves' disease at a
      tertiary hospital and subsequently had one or more pregnancies. RESULTS: A total
      of 29 women were identified, each of whom had at least one pregnancy since
      receiving definitive treatment for Graves' disease: there were a total of 49
      pregnancies (22 in the surgical group and 27 in the radioiodine group). Both
      groups had high rates of hypothyroidism documented during pregnancy (47 and 50%,
      respectively). The surgical group was more likely to be euthyroid around the time
      of conception. Less than half of the women were referred to an endocrinologist or
      had TRAb measured during pregnancy. Neonatal thyroid function was measured in one
      third of live births. One case of neonatal thyrotoxicosis was identified.
      CONCLUSIONS: Adherence to the current American Thyroid Association guidelines is
      poor. Further education of both patients and clinicians is important to ensure
      that treatment of women during pregnancy after definitive treatment follows the
      currently available guidelines.

PMID- 24576234
TI  - 'Super-diversity' must be recognised by policymakers.

PMID- 24576237
TI  - GP contract will increase workload for other staff.

PMID- 24576226
TI  - The rate of high ovarian response in women identified at risk by a high serum AMH
      level is influenced by the type of gonadotropin.
AB  - The aim was to compare ovarian response and clinical outcome of potential high
      responders after stimulation with highly purified menotropin (HP-hMG) or
      recombinant follicle-stimulating hormone (rFSH) for in vitro
      fertilisation/intracytoplasmic sperm injection. Retrospective analysis was
      performed on data collected in two randomized controlled trials, one conducted
      following a long GnRH agonist protocol and the other with an antagonist protocol.
      Potential high-responders (n = 155 and n = 188 in the agonist and antagonist
      protocol, respectively) were defined as having an initial anti-Mullerian hormone
      (AMH) value >75th percentile (5.2 ng/ml). In both protocols, HP-hMG stimulation
      in women in the high AMH category was associated with a significantly lower
      occurrence of high response (>=15 oocytes retrieved) than rFSH stimulation; 33%
      versus 51% (p = 0.025) and 31% versus 49% (p = 0.015) in the long agonist and
      antagonist protocol, respectively. In the potential high-responder women, trends
      for improved live birth rate were observed with HP-hMG compared with rFSH (long
      agonist protocol: 33% versus 20%, p = 0.074; antagonist protocol: 34% versus 23%,
      p = 0.075; overall population: 34% versus 22%, p = 0.012). In conclusion, the
      type of gonadotropin used for ovarian stimulation influences high-response rates
      and potentially clinical outcome in women identified as potential high
      responders.

PMID- 24576241
TI  - Tea and company.

PMID- 24576244
TI  - Practice question: how can observations of care help me improve my practice?

PMID- 24576246
TI  - Dementia-friendly neighbourhoods.
AB  - Six research projects that will improve understanding of dementia are to receive
      L20 million in funding from the UK government. The projects, which will be
      overseen by the National Institute for Health Research and the Economic and
      Social Research Council, include investigations into creating dementia-friendly
      neighbourhoods; the lifestyle changes that can reduce the risk of developing the
      condition; training care home staff to support patients who become agitated;
      improving predictions of the future financial costs of dementia; living well with
      the condition; and the effects of visual aids on wellbeing and quality of life. 

PMID- 24576247
TI  - Evaluation of dementia training for staff in acute hospital settings.
AB  - The development, pilot and evaluation of a brief psychosocial training
      intervention (BPTI) for staff working with people with dementia in an acute
      hospital setting are described. The project had two phases. Phase one involved
      adapting an existing competency framework and developing the BPTI using focus
      groups. For the pilot and evaluation, in phase two, a mixed methods approach was
      adopted using self-administered standardised questionnaires and qualitative
      interviews. Qualitative analysis suggested that delivering skills-based training
      can develop communication, problem-solving and self-directed learning skills;
      benefit staff in terms of increased knowledge, skills and confidence; and be
      problematic in the clinical area in terms of time, organisation and the physical
      environment. These factors must be taken into consideration when delivering
      training. These changes were not reflected in the quantitative results and
      measures were not always sensitive to changes in this setting. Definitive
      conclusions cannot be drawn about the efficacy of the intervention, due to the
      contradictory outcomes between the quantitative and qualitative data. Further
      developments and research are required to explore how staff and organisations can
      be supported to deliver the best possible care. 

PMID- 24576248
TI  - Family care experiences in nursing home facilities.
AB  - AIM: To explore relatives' involvement in the care of older adults admitted to
      residential settings. METHOD: A qualitative approach using semi-structured
      interviews was adopted. Data were analysed using content thematic analysis.
      FINDINGS: Content thematic analysis revealed that participants experienced a
      change in role when their relatives were admitted to residential care. Three
      major themes emerged: family involvement, family-centred care, and communication.
      The importance of communicating with staff was emphasised by relatives.
      CONCLUSION: The transition from home to residential care is a challenging time
      for residents and families. Nurses need to communicate with families and adopt a
      collaborative, integrated approach to care.

PMID- 24576249
TI  - Attitudes towards caring for older people in Scotland, Sweden and the United
      States.
AB  - AIM: To explore the attitudes of nurses and nursing students in Scotland, Sweden
      and the US towards working with older people. METHOD: This quantitative study
      used the 20-item Multifactorial Attitudes Questionnaire (MAQ) to elicit attitudes
      on ageism, resources, working environment, education and professional esteem.
      Researchers from each country distributed the questionnaires to nursing students
      and nurses, giving a convenience sample of 1,587 respondents. Data were entered
      on the Statistical Package for Social Sciences version 18 and merged into one
      large dataset. RESULTS: Scottish participants had the highest (positive) and
      Swedish participants the lowest mean MAQ score. The Kruskal-Wallis test showed
      significant differences in mean scores across the countries in 18 of the 20
      statements, even when controlling for age and experience. Most participants gave
      positive responses, but agreed that negative attitudes towards working with older
      people pervade among peers due to working conditions, poor career prospects and a
      perceived lack of professional esteem. CONCLUSION: Inspirational educators,
      excellent clinical placements and increasing the professional esteem of those
      working with older people are required to promote the specialty as an attractive
      career option.

PMID- 24576250
TI  - Make nursing visible.

PMID- 24576251
TI  - Polypharmacy, drug-drug interactions, and potentially inappropriate medications
      in older adults with human immunodeficiency virus infection.
AB  - OBJECTIVES: To describe the frequency of medication-related problems in older
      adults with human immunodeficiency virus (HIV) infection. DESIGN: Retrospective
      chart review. SETTING: Community. PARTICIPANTS: HIV-positive individuals aged 60
      and older and age- and sex-matched HIV-negative individuals. MEASUREMENTS: Total
      number of medications, potentially inappropriate medications (PIMs) according to
      the modified Beers Criteria, anticholinergic drug burden according to the
      Anticholinergic Risk Scale (ARS), and drug-drug interactions using the Lexi
      Interact online drug interactions database. RESULTS: Of 89 HIV-positive
      participants, most were Caucasian (91%) and male (94%), with a median age of 64
      (range 60-82). Common comorbidities included hyperlipidemia, hypertension, and
      depression. Participants were taking a median of 13 medications (range 2-38), of
      which only a median of four were antiretrovirals. At least one PIM was prescribed
      in 46 participants (52%). Sixty-two (70%) participants had at least one Category
      D (consider therapy modification) drug-drug interaction, and 10 (11%) had a
      Category X (avoid combination) interaction. One-third of these interactions were
      between two nonantiretroviral medications. Fifteen participants (17%) had an ARS
      score of 3 or greater. In contrast, HIV-negative participants were taking a
      median of six medications, 29% had at least one PIM, and 4% had an ARS score of 3
      or greater (P < .05 for each comparison, except P = .07 for anticholinergic
      burden). CONCLUSION: HIV-positive older adults have a high frequency of
      medication-related problems, of which a large portion is due to medications used
      to treat comorbid diseases. These medication issues were substantially higher
      than HIV-negative participants. Attention to the principles of geriatric
      prescribing is needed as this population ages in order to minimize complications
      from multiple medication use.

PMID- 24576252
TI  - Prevalence of esophageal ulceration after atrial fibrillation ablation with the
      hot balloon ablation catheter: what is the value of esophageal cooling?
AB  - BACKGROUND: Little is known about luminal esophageal temperature (LET) monitoring
      during catheter ablation for atrial fibrillation (AF) using the radiofrequency
      hot balloon (RHB) technology. OBJECTIVE: The aim of this study is to investigate
      the impact of the use of a unique esophageal cooling method during RHB ablation.
      METHODS AND RESULTS: In this observational study, 318 consecutive patients (231
      men; mean age, 63 +/- 9 years) with symptomatic, drug-refractory, paroxysmal (n =
      183) or persistent (n = 135) AF underwent RHB ablation with LET monitoring
      followed by a postprocedural, nonsymptom-driven esophageal endoscopy within 3
      days of the ablation procedure. The patients have been divided into 3 groups. The
      first 22 patients treated are in Group A (n = 22) and had only LET monitoring
      without cooling of the esophagus. In Groups B (n = 128) and C (n = 168), patients
      had LET monitoring with cooling of the esophagus when the LET exceeded 43 
      degrees C and 39  degrees C, by infusion of cooled saline mixed with
      Gastrographin or Iopamidol, respectively. Group A had a higher risk of esophageal
      ulceration among the 3 groups (P < 0.0001). Saline infusion cooling initiated
      when the LET exceeded 43  degrees C (Group B) was not as safe as saline infusion
      cooling initiated when the LET exceeded 39  degrees C (Group C), demonstrated by
      the Group C minimum ulceration score and LET measurements while ablating the left
      superior pulmonary vein (LSPV) and left inferior pulmonary vein (LIPV) (P <
      0.0001). CONCLUSION: Cooling the esophagus by a mix of Iopamidol and saline
      infusion when the LET exceeds 39  degrees C during RHB ablation may decrease the
      incidence and severity of esophageal thermal injury.

PMID- 24576254
TI  - TNF-alpha inhibition elicited by mansoins A and B, heterotrimeric flavonoids
      isolated from Mansoa hirsuta.
AB  - Mansoins A (1) and B (2) isolated from the fruits of Mansoa hirsuta represent new
      glucosylated heterotrimeric flavonoids with a flavanone core linked to two 1,3
      diarylpropane C6-C3-C6 units. Their structures and absolute configurations were
      established by analysis of their NMR and electronic circular dichroism
      spectroscopic data. Compounds 1 and 2 inhibited TNF-alpha release by LPS
      stimulated THP-1 cells with different potencies, with mansoin B (2) being active
      at lower concentrations than mansoin A (1) (IC50 values 20.0+/-1.4 and 48.1+/-1.8
      MUM, respectively). These results indicate potential anti-inflammatory properties
      for this structural type of oligoflavonoids, especially for mansoin B (2).

PMID- 24576255
TI  - Ultratrace determination of silver, gold, and iron oxide nanoparticles by micelle
      mediated preconcentration/selective back-extraction coupled with flow injection
      chemiluminescence detection.
AB  - A new method has been developed for the ultrasensitive determination of silver,
      gold, and iron oxide nanoparticles in environmental samples. Cloud point
      extraction was optimized and used as a means to extract and preconcentrate all
      nanoparticle species simultaneously from the same sample. The extracted
      nanoparticles were sequentially isolated from the surfactant-rich phase by a new
      selective back-extraction procedure and dissociated into their precursor metal
      ions. Each ion solution was injected in a flow injection analysis (FIA) manifold,
      accommodating the chemiluminogenic oxidation of luminol, in order to amplify
      chemiluminescence (CL) emission in a manner proportional to its concentration.
      Under the optimum experimental conditions, the detection limits were brought down
      to the picomolar and femtomolar concentration levels with satisfactory analytical
      features in terms of precision (2.0-13.0%), selectivity against dissolved ions,
      and recoveries (74-114%). The method was successfully applied to the
      determination of iron oxide, silver, and gold nanoparticles in environmental
      samples of different complexity, ranging from unpolluted river water to raw
      sewage. The developed method could also serve as a basis for future deployment of
      molecular spectrometry detectors for the selective determination and speciation
      analysis of nanoparticles in environmental applications. 

PMID- 24576256
TI  - Penicillitone, a potent in vitro anti-inflammatory and cytotoxic rearranged
      sterol with an unusual tetracycle core produced by Penicillium purpurogenum.
AB  - A rearranged sterol with an unusual tetracycle core skeleton, penicillitone (1),
      and a new sterol, penicillisterol (2), were obtained from the culture of the
      fungus Penicillium purpurogenum SC0070. Their structures were characterized by
      spectroscopic analysis, DFT/TDDFT compuations, and X-ray diffraction. Compound 1
      demonstrated potent inhibitory effects on tumor cell growth and key pro
      inflammatory cytokine production in macrophages. A biogenetic pathway with
      oxidative cleavage and vinylogous aldol addition as key reactions is proposed for
      1. 

PMID- 24576257
TI  - Concurrent relations among cigarette smoking status, resting heart rate
      variability, and erectile response.
AB  - INTRODUCTION: Heart rate variability (HRV) is a marker of sympathovagal balance;
      it has been implicated in erectile function and is also altered by tobacco use.
      Furthermore, smoking and erectile health are strongly related, given that smokers
      are at increased risk for erectile dysfunction. Few studies have explored the
      interrelationships between smoking, HRV, and erectile function concurrently. AIM:
      The aim of this study was to examine potential mechanisms underlying tobacco's
      effects on penile hemodynamics by exploring the mediating role of HRV. METHODS:
      The sample comprised 119 men (smokers = 64; nonsmokers = 55) (mean age 28.90
      years; standard deviation (SD) 11.68; range 18-58) selected from the control
      conditions of three previously published experiments. Participants were free from
      a history of cardiovascular disease, myocardial infarct, and/or
      cardiac/cardiovascular medication use. During a laboratory visit, self-report,
      anthropometric, cardiovascular, and electrocardiographic data were assessed, as
      well as sexual arousal responses elicited from viewing an erotic film. MAIN
      OUTCOME MEASURES: Objective sexual arousal indices (circumferential change via
      penile plethysmography), self-reported erectile function (per the erectile
      function domain score of the International Index of Erectile Function [IIEF-EF]),
      and time- (SD of beat-to-beat intervals) and frequency-domain parameters of HRV
      (ratio of low-frequency [LF] power to high-frequency [HF] power [LF/HF ratio])
      were assessed. RESULTS: Being a current long-term cigarette smoker was associated
      with dysregulated sympathovagal balance (higher LF/HF ratios, indicative of
      sympathetic nervous system dominance), which in turn showed inverse relations
      with magnitude of erectile tumescence. HRV did not mediate relations between
      tobacco use and either IIEF-EF scores or resting penile circumference.
      CONCLUSIONS: Findings suggest that dysfunctional cardiac autonomic tone may be an
      underlying mechanism by which tobacco exerts its deleterious effects on erectile
      health. Further research is necessary to determine whether this relationship is
      mechanistic in nature, or whether it is better explained by other health factors.

PMID- 24576258
TI  - Increasing susceptibility of nitric oxide-mediated inhibitory platelet signaling
      during storage of apheresis-derived platelet concentrates.
AB  - BACKGROUND: Storage of platelets (PLTs) affects PLT integrity and functionality,
      a process named the PLT storage lesion. Normal PLT function essentially depends
      on the balanced interaction of activating and inhibitory signaling pathways. As
      there are poor data on the alterations of inhibitory signaling during storage of
      PLT concentrates, this study investigates the modulation capability of the cyclic
      nucleotide-mediated inhibitory pathways by use of the nitric oxide donor
      diethylamine diazenium diolate (DEA/NO). STUDY DESIGN AND METHODS: PLTs were
      obtained from whole blood (WB) and from apheresis-derived PLT concentrates (APCs)
      stored for 0, 2, and 5 days. Vasodilator-stimulated phosphoprotein (VASP)
      phosphorylation, cyclic nucleotide concentrations, fibrinogen binding, and
      agonist-induced aggregation were measured without or after stimulation with
      DEA/NO. RESULTS: DEA/NO-induced VASP phosphorylation was significantly higher in
      PLTs from APCs on Days 2 and 5 compared to WB, conditioned by a stronger increase
      of cyclic guanosine monophosphate (cGMP), but not cyclic adenosine monophosphate
      (cAMP), in stored PLTs. A quantity of 5 nmol/L DEA/NO neither influenced thrombin
      receptor activator peptide 6 and collagen-induced aggregation nor fibrinogen
      binding in freshly collected PLTs, whereas it significantly inhibited both in
      stored PLTs. CONCLUSION: Stored PLTs showed an impairment of intracellular cGMP
      regulation, resulting in exceeding inhibition of agonist-induced aggregation and
      fibrinogen binding in the course of storage. The observed effects could be an
      important mechanism contributing to the storage lesion with reduced activating
      potential of PLTs.

PMID- 24576260
TI  - Trends in access to water supply and sanitation in 31 major sub-Saharan African
      cities: an analysis of DHS data from 2000 to 2012.
AB  - BACKGROUND: By 2050, sub-Saharan Africa's (SSA) urban population is expected to
      grow from 414 million to over 1.2 billion. This growth will likely increase
      challenges to municipalities attempting to provide access to water supply and
      sanitation (WS&S). This study aims to characterize trends in access to WS&S in
      SSA cities and identify factors affecting those trends. METHODS: DHS data
      collected between 2000 and 2012 were used for this analysis of thirty-one cities
      in SSA. Four categories of household access to WS&S were studied using data from
      demographic and health surveys--these included: 1) household access to an
      improved water supply, 2) household's time spent collecting water, 3) household
      access to improved sanitation, and 4) households reporting to engage in open
      defecation. An exploratory analysis of these measures was then conducted to
      assess the relationship of access to several independent variables. RESULTS:
      Among the 31 cities, there was wide variability in coverage levels and trends in
      coverage with respect to the four categories of access. The majority of cities
      were found to be increasing access in the categories of improved water supply and
      improved sanitation (65% and 83% of cities, respectively), while fewer were
      making progress in reducing the amount of time spent collecting water and
      reducing open defecation (50% and 38% of cities, respectively). Additionally, the
      prevalence of open defecation in study cities was found to be, on average,
      increasing. CONCLUSIONS: Based on DHS data, cities appeared to be making the most
      progress in gaining access to WS&S along metrics which reflect specified targets
      of the Millennium Development Goals. Nearly half of the cities, however, did not
      make progress in reducing open defecation or the time spent collecting water.
      This may reflect that the MDGs have led to a focus on "improved" services while
      other measures, potentially more relevant to the extreme poor, are being
      neglected. This study highlights the need to better characterize access, beyond
      definitions of improved and unimproved, as well as the need to target resources
      to cities where changes in WS&S access have stalled, or in some cases regressed.

PMID- 24576262
TI  - Clusters of coarse-grained water molecules.
AB  - Global optimization for molecular clusters can be significantly more difficult
      than for atomic clusters because of the coupling between orientational and
      translational degrees of freedom. A coarse-grained representation of the
      potential can reduce the complexity of this problem, while retaining the
      essential features of the intermolecular interactions. In this study, we use a
      basin-hopping algorithm to locate putative global minima for clusters of coarse
      grained water molecules modeled using a monatomic water potential for cluster
      sizes 3 <= N <= 55. We characterize these structures and identify structural
      trends using ideas from graph theory. The agreement with atomistic results and
      experiment is rather patchy, which we attribute to the tetrahedral bias in the
      three-body potential that results in too few nearest neighbor contacts and
      premature emergence of bulk-like structure. In spite of this issue, the results
      offer further useful insight into the relationship between the structure of
      clusters and bulk phases, and the mathematical form of a widely used model
      potential. 

PMID- 24576261
TI  - A Rare Case of Eccrine Porocarcinoma of the Eyelid.
AB  - BACKGROUND: To report a rare case of eyelid eccrine porocarcinoma and compare
      this to previous documented cases in the literature. MAIN OBSERVATIONS: We report
      a case of an 86-year-old man who presented with three months' history of
      irritation in the right eye, who was found to have an irregular nodule on lower
      eyelid, which was later diagnosed as eccrine porocarcinoma (EPC). The lesion was
      excised and the defect repaired with Hughes flap. A computerized tomography (CT)
      scan of the head, neck, and chest showed no metastasis and no lymphadenopathy.
      There was no evidence of recurrence after 18 months of follow-up. CONCLUSION: To
      date, there have been only six cases of eyelid EPC reported in the literature.
      EPC has significant risk of recurrence and metastases after local excision. It is
      therefore important to consider it in the differential diagnosis of malignant
      eyelid tumour. A histological diagnosis should prompt wide margin excision,
      assessment of the patient for regional lymph node involvement, and imaging for
      metastatic disease.

PMID- 24576259
TI  - Anaesthetic, analgesic and cardiorespiratory effects of intramuscular
      medetomidine-ketamine combination alone or with morphine or tramadol for
      orchiectomy in cats.
AB  - OBJECTIVES: To compare the anaesthetic, analgesic and cardiorespiratory effects
      of intramuscular (IM) medetomidine and ketamine administered alone or combined
      with morphine or tramadol, for orchiectomy in cats. STUDY DESIGN: Randomised,
      blinded, prospective clinical study. ANIMALS: Thirty client-owned cats. MATERIALS
      AND METHODS: Cats (n = 10 in each group) received a combination of medetomidine
      (60 MUgkg(-1) ) and ketamine (10 mg kg(-1) ) alone (MedK); combined with morphine
      (0.2 mg kg(-1) ) (MedKM), or combined with tramadol (2 mg kg(-1) ) (MedKT) IM.
      Time of induction, surgical and recovery events were recorded, and physiological
      parameters measured and recorded. Analgesia was evaluated with a visual analogue
      scale, a composite scoring system and the von Frey mechanical threshold device,
      every hour from three to eight hours post-drug administration injection. Data
      were analyzed with a linear mixed model, Kruskal-Wallis or Chi-square tests (p <
      0.05). RESULTS: Median (IQR) induction and recovery times (minutes) were not
      significantly (p = 0.125) different between groups: 5.6 (2.7-8.0), 7.4 (5.1-9.6)
      and 8.0 (5.8-14.9) for induction and 128.5 (95.1-142.8), 166.4 (123.1-210.0) and
      142.9 (123.4-180.2) for recovery, with MedK, MedKT and MedKM, respectively. Two
      cats (MedKM) required alfaxalone for endotracheal intubation. In all groups,
      three or four cats required additional isoflurane for surgery. Arterial oxygen
      tension overall (mean +/- SD: 66 +/- 2 mmHg) was low. Surgery resulted in
      increased systolic arterial blood pressure (p < 0.001), haemoglobin saturation (p
      < 0.001), respiratory (p = 0.003) and heart rates (p = 0.002). Pain scores did
      not differ significantly between groups. Von Frey responses decreased over time;
      changes over time varied by treatment (p < 0.001), MedK returning to baseline
      values more rapidly than MedKM and MedKT. No cat required rescue analgesics.
      CONCLUSION AND CLINICAL RELEVANCE: All three protocols can provide adequate
      anaesthesia and analgesia for orchiectomy in cats. However, rescue intervention
      to maintain surgical anaesthesia may be required in some cats. Oxygen
      supplementation is advised.

PMID- 24576263
TI  - Pyoderma gangrenosum-like CD30+  cutaneous T-cell lymphoma in a patient with
      mycosis fungoides.

PMID- 24576264
TI  - Preface for buccal drug delivery theme issue.
AB  - During the past years, buccal drug delivery has attracted the attention of
      researchers looking for alternative delivery routes of administration. As an
      alternative to oral drug delivery, the buccal mucosal route avoids the passage
      through the acidic gastric environment, intestinal and bacterial enzymatic
      activity, absorption issues associated with the intestinal epithelium (e.g. P
      glycoprotein efflux), and the first pass metabolism of the liver. Therefore, the
      buccal route could be a good delivery route for macromolecules and other drugs
      not compatible with the gastrointestinal tract environment. This "Buccal Drug
      Delivery" special edition of Drug Development and Industrial Pharmacy aims to
      bring together a range of different aspects relevant to the growing field of
      buccal drug delivery. The special edition includes thorough reviews of the
      literature, as well as original research articles touching on most prominent
      features related to buccal drug delivery systems, such as the move toward the use
      of nanotechnology in different ways to facilitate buccal drug delivery with the
      potential to prompt future product developments.

PMID- 24576265
TI  - Development of topical hydrogels of terbinafine hydrochloride and evaluation of
      their antifungal activity.
AB  - The purpose of this study was to prepare hydrogels and microemulsion (ME)-based
      gel formulations containing 1% terbinafine hydrochloride (TER-HCL) and to
      evaluate the use of these formulations for the antifungal treatment of fungal
      infections. Three different hydrogel formulations were prepared using chitosan,
      Carbopol(r) 974 and Natrosol(r) 250 polymers. A pseudo-ternary phase diagram was
      constructed, and starting from ME formulation, a ME gel form containing 1%
      Carbopol 974 was prepared. We also examined the characteristic properties of the
      prepared hyrogels. The physical stability of hydrogels and the ME -based gels
      were evaluated after storage at different temperatures for a period of 3 months.
      The release of TER-HCL from the gels and the commercial product (Lamisil(r)) was
      carried out by using a standard dialysis membrane in phosphate buffer (pH 5.2) at
      32  degrees C. The results of the in vitro release study showed that the Natrosol
      gel released the highest amount of drug, followed by Carbopol gel, chitosan gel,
      commercial product, and the microoemulsion-based gel in that order. In vitro
      examination of antifungal activity revealed that all the prepared and commercial
      products were effective against Candida parapsilosis, Penicillium, Aspergillus
      niger and Microsporum. These results indicate that the Natrosol(r)-based hydrogel
      is a good candidate for the topical delivery of TER-HCL. 

PMID- 24576266
TI  - Mucoadhesive polymers for buccal drug delivery.
AB  - Raising the concept of mucoadhesion in the 1980s, the use of mucoadhesive
      polymers for buccal drug delivery has been the subject of interest. Buccal route
      is one of the non-invasive routes comprising several advantages such as targeting
      the specific tissue (I), bypassing the first-pass effect (II) as well as higher
      patient compliance (III) and higher bioavailability (IV) have rendered
      administration route feasible for a variety of drugs. This review highlights the
      use of mucoadhesive polymers in buccal drug delivery. An overview of the oral
      mucosa's anatomy, theories of mucoadhesion as well as mucoadhesive polymers is
      given within this review. Furthermore, recent advantages in mucoadhesive polymers
      according to the variety of drug delivery forms are presented.

PMID- 24576267
TI  - In vitro comparative evaluation of monolayered multipolymeric films embedded with
      didanosine-loaded solid lipid nanoparticles: a potential buccal drug delivery
      system for ARV therapy.
AB  - Drug delivery via the buccal route has emerged as a promising alternative to oral
      drug delivery. Didanosine (DDI) undergoes rapid degradation in the
      gastrointestinal tract, has a short half-life and low oral bioavailability,
      making DDI a suitable candidate for buccal delivery. Recent developments in
      buccal drug delivery show an increased interest toward nano-enabled delivery
      systems. The advantages of buccal drug delivery can be combined with that of
      nanoparticulate delivery systems to provide a superior delivery system. The aim
      of this study was to design and evaluate the preparation of novel nano-enabled
      films for buccal delivery of DDI. Solid lipid nanoparticles (SLNs) were prepared
      via hot homogenization followed by ultrasonication and were characterized before
      being incorporated into nano-enabled monolayered multipolymeric films (MMFs).
      Glyceryl tripalmitate with Poloxamer 188 was identified as most suitable for the
      preparation of DDI-loaded SLNs. SLNs with desired particle size (PS) (201 nm),
      polydispersity index (PDI) (0.168) and zeta potential (-18.8 mV) were
      incorporated into MMFs and characterized. Conventional and nano-enabled MMFs were
      prepared via solvent casting/evaporation using Eudragit RS100 and hydroxypropyl
      methylcellulose. Drug release from the nano-enabled films was found to be faster
      (56% versus 20% in first hour). Conventional MMFs exhibited higher mucoadhesion
      and mechanical strength than nano-enabled MMFs. SLNs did not adversely affect the
      steady state flux (71.63 +/- 13.54 ug/cm(2) h versus 74.39 +/- 15.95 ug/cm(2) h)
      thereby confirming the potential transbuccal delivery of DDI using nano-enabled
      MMFs. Nano-enabled buccal films for delivery of DDI can be successfully prepared,
      and these physico-mechanical studies serve as a platform for future formulation
      optimization work in this emerging field.

PMID- 24576268
TI  - 'Bamboo spine', a thing of the past?

PMID- 24576269
TI  - Conflict of interest, an unspoken reality in science.

PMID- 24576270
TI  - Antioxidant profile in patients with complex regional pain syndrome type I.
AB  - OBJECTIVE: Complex regional pain syndrome (CRPS) type I is one of the most
      important problems with regard to physical medicine and rehabilitation. CRPS may
      cause not only higher therapeutic costs but also greater work time loss. The
      mechanism and pathogenesis of CRPS still remains unknown. Some findings
      indicating oxidative stress have been reported. This study was carried out to
      determine the role of oxidative stress in patients with CRPS. MATERIALS AND
      METHODS: Twenty patients (13 women and seven men) with CRPS and 20 age- and sex
      matched healthy controls were enrolled in this study. Complex regional pain
      syndrome was diagnosed according to the modified International Association for
      the Study of Pain (IASP) criteria. We evaluated demographic, clinical and
      laboratory characteristics of the patients. Antioxidant enzymatic activities
      consisting of serum superoxide dismutase (SOD), glutathion peroxidase (GPX) and
      glutathione S-transferase (GST) activities were measured using appropriate
      methods and compared with healthy controls. RESULTS: The mean age of the patients
      was 39.5 years and the mean duration of symptoms was 5.5 months. Complex regional
      pain syndrome devoleped after a traumatic event in 90% of patients. In 10% of
      patients there were no traumatic events. SOD, GPX and GST levels were
      significantly higher in patients with CRPS than healthy controls (P = 0.012, P =
      0.036 and P = 0.016, respectively). CONCLUSION: Our findings suggest a possible
      role of oxidative stress in the pathogenesis of CRPS.

PMID- 24576271
TI  - Treatment of low back pain: randomized clinical trial comparing a
      multidisciplinary group-based rehabilitation program with oral drug treatment up
      to 12 months.
AB  - BACKGROUND: This study aimed to examine the effects of a multidisciplinary
      treatment program on health-related quality of life of Iranian patients living
      with chronic low back, at 12 months follow-up. METHODS: This study is an extended
      follow-up of an original randomized, controlled trial with registration number
      NCT00600197. In the present study 87 patients in an intervention group and 91
      patients in a control group were assessed at 12 months follow-up. The
      intervention was a group-based multidisciplinary rehabilitation program which
      continued by monthly motivational consultation by telephone from 6 to 12 months
      after intervention. Data from three standard measures, Short Form 36 (SF-36), QDS
      and RDQ were collected at 3, 6 and 12 months follow-up and analyzed through
      repeated measures analysis of variance. RESULTS: Despite the similarity between
      the two groups who completed the 6 month follow-up in terms of all baseline
      variables, there were significant differences between the two groups in all
      domains of the SF-36 scale, as well as QDS and RDQ scales (P < 0.05). Also, there
      were differences within each group over time in the SF-36 domains and disability
      measurements (P < 0.05). The physical function mean score differed significantly
      when the interaction between groups and time points was examined (P = 0.02).
      CONCLUSION: This study indicates that the multidisciplinary program could improve
      the domains of health related quality of life and disability in chronic low back
      pain patients up to 12 months.

PMID- 24576272
TI  - Working life and physical activity in ankylosing spondylitis pre and post anti
      tumor necrosis factor-alpha therapy.
AB  - AIM: To assess effects of ankylosing spondylitis (AS) on working life and
      physical activity in Australia; to quantify changes in working life and physical
      activity that occur after anti-tumor necrosis factor-alpha (TNF-alpha) treatment;
      and to assess efficacy of anti-TNF-alpha therapy for AS in an Australian context.
      METHODS: This is a multi-centre observational study of people with AS on anti-TNF
      alpha therapy. All participants satisfied the New York Modified Criteria and had
      active and refractory disease at anti-TNF-alpha therapy commencement.
      Participation involved a standardized interview, a metrology assessment,
      assessment of disease remission and medical record review. Interviews and
      patients' records were used to compare working life (employment, sick leave and
      productivity) and physical activity (participation rate, hours/week, and physical
      intensity) between the pre-AS, post-AS and post-anti-TNF-alpha therapy periods.
      RESULTS: Fifty-two patients took part. Participants were on average 44.8 years
      old, predominately male (86.5%) and had been on anti-TNF-alpha therapy for 29
      months; 39% were in partial remission and 75% had 50% reduction in the Bath
      Ankylosing Spondylitis Disease Activity Index (BASDAI). Responders to anti-TNF
      alpha therapy were 10.5 years younger than non-responders (P = 0.004). Post-anti
      TNF-alpha therapy participants gained 6.6 h/week of work (P = 0.02), and
      productivity improved 31% (P < 0.001) compared to immediately prior to commencing
      treatment. Physical activity participation increased from 71% to 85% (P = 0.039)
      and activity intensity increased by 33% (P = 0.002) post-treatment. Participants
      gained 1.8 h/week of sport (P = 0.001) and 2.2 h/week of recreational physical
      activity (P < 0.001). CONCLUSIONS: Australians with AS have their working life
      and physical activity severely affected by this disease. Treatment with anti-TNF
      alpha therapy results in significant improvement in these parameters.

PMID- 24576273
TI  - Spondyloarthritis Research Consortium of Canada (SPARCC) enthesitis index in
      Turkish patients with ankylosing spondylitis: relationship with disease activity
      and quality of life.
AB  - AIM: The aim of this study was to investigate the relationship between
      Spondyloarthritis Research Consortium of Canada (SPARCC) enthesitis index and
      disease activity and health-related quality of life in patients with ankylosing
      spondylitis (AS). METHODS: Eighty-six AS patients not receiving antitumour
      necrosis factor (TNF) therapy were included in the study. Spinal pain by visual
      analogue scale (pain VAS rest and activity), disease activity by Bath Ankylosing
      Spondylitis Disease Activity Index (BASDAI), functional capacity by Bath
      Ankylosing Spondylitis Functional Index (BASFI), enthesitis severity by SPARCC
      index, quality of life by Short Form-36 (SF-36), and Bath Ankylosing Spondylitis
      Metrology Index (BASMI) were assessed in patients. In the laboratory evaluations,
      the erythrocyte sedimentation rates and serum C-reactive protein levels of the
      patients were determined. RESULTS: All participants were aged between 18 and 65
      years, with a mean age of 36.9 +/- 11.13 years. The most frequent region of
      enthesitis was Achilles tendon insertion into calcaneum (55.8%). Pain VAS rest
      and activity, BASFI and all parameters of SF-36 were significantly different in
      AS patients with and without enthesitis. SPARCC index was significantly
      correlated with pain VAS activity (P < 0.05), pain VAS rest, BASDAI, BASFI and
      all parameters of SF-36 (P < 0.001). There were no correlations between SPARCC
      index and BASMI, disease duration and laboratory parameters (P > 0.05).
      CONCLUSION: The clinical assessment of enthesitis in AS is an important outcome
      measure, and enthesitis indexes such as SPARCC enthesitis index can be valuable
      tools in the evaluation of disease activity in AS patients not receiving anti-TNF
      therapy.

PMID- 24576274
TI  - Correlation of articular involvement, skin disfigurement and unemployment with
      depressive symptoms in patients with systemic sclerosis: a hospital sample.
AB  - BACKGROUND: Systemic sclerosis (SSc) is a connective tissue disease associated
      with increased functional impairment, body image distress due to skin lesions,
      and psychosocial comorbidity, particularly depression. Prevalence of depressive
      symptoms in SSc patients ranges from 36% to 65% and it contributes to the
      worsening of any aspect of the disease. The aim of this study was to investigate
      the prevalence and clinical and non-clinical correlates of depressive symptoms in
      a sample of outpatients with SSc. METHODS: Seventy-eight consecutive SSc
      outpatients were recruited from February 2005 to July 2007. Socio-demographic and
      SSc-related clinical data were collected, including a modified Rodnan Skin Score,
      the Valentini Disease Activity Index and psycho-metric assessment of disability
      and pain. Depressive symptoms were assessed using the Beck Depression Inventory
      (BDI). Two questions on perception of support from relatives and impact of
      disfigurements were also directly addressed to subjects. RESULTS: The BDI mean
      score was 10.5 (+/- 8.3), with 36 subjects (46.2%) scoring above clinical
      significance. Unemployment, increased disability, pain, disease activity and
      articular involvement were significantly associated with more depressive
      symptoms. Older age, unemployment and more depressive symptoms were also related
      with complaints of disfigurements due to skin involvement. CONCLUSIONS:
      Depression is an influential prognostic factor in SSc. The present study
      contributes to the knowledge of the relationship between depression and clinical
      features routinely collected in rheumatology settings in order to develop a
      standardized assessment of psychosocial distress in routine rheumatologic
      procedures.

PMID- 24576275
TI  - A fracture prevention service reduces further fractures two years after incident
      minimal trauma fracture.
AB  - AIM: To evaluate the impact of a fracture prevention clinic service on initiation
      of treatment, continuing treatment and subsequent minimal trauma fractures (MTF).
      METHOD: Participants were people aged 50 and over, with a minimal trauma fracture
      presenting to the Emergency Department (ED) in a large tertiary referral hospital
      in New South Wales, Australia, between February 2007 and March 2009. A cohort of
      patients who attended a Fracture Prevention Clinic (clinic group) were compared
      with a cohort who did not attend the clinic (non-clinic group). A telephone
      questionnaire was conducted with participants or their carers between December
      2010 and April 2011 at least 12 months post-fracture presentation. Questionnaire
      items included demographics, fracture types, osteoporosis treatment, recurrent
      fractures and smoking and dietary habits. Data were compared using chi-squared
      test for categorical variables and Student's t-test or Mann-Whitney U-test for
      continuous variables. RESULTS: Two hundred and fourteen clinic attendees and 220
      non-clinic attendees were surveyed between 12 and 40 months (mean 24 months) post
      initial fracture. New fracture rates were lower in the clinic group (5.1%) than
      the non-clinic group (16.4%, P < 0.001). Treatment rates for bone fragility were
      higher in the clinic group (81.3%) than in the non-clinic group (54.1%, P <
      0.001) with 66.8% of the clinic group and 34.1% of the non-clinic group on a
      bisphosphonate or strontium ranelate at the time of the survey (P < 0.001).
      CONCLUSION: Patients managed by a fracture prevention clinic service following a
      MTF have fewer new fractures and are more likely to be on treatment for bone
      fragility.

PMID- 24576276
TI  - The reliability of the clinical examination for detecting Baker's cyst in
      asymptomatic fossa.
AB  - OBJECTIVE: To compare physical examination and ultrasonographic (US) examination
      for detecting Baker's cyst (BC) in asymptomatic popliteal fossa. METHODS:
      Popliteal fossa was examined in a total of 220 knees in 110 patients with knee
      pain/osteoarthritis (OA) and non-OA individuals. Clinical examination was
      performed by two independent physicians and US examination was performed by a
      third blinded physician. RESULTS: Examiner A found 25 BC, examiner B found 30 BC
      in 220 knees examined (kappa = 0.35; 95% CI; 0.14-0.56) and inter-observer
      reliability was moderate. When US examination taken as the reference, receiver
      operating characteristic analysis revealed an area under the curve of 0.58 (95%
      CI; 0.51-0.65) for examiner A and 0.57 (95% CI; 0.50-0.64) for examiner B,
      showing a weak agreement between physical examination and US assessment.
      CONCLUSION: This study demonstrates that many patients may have BCs without any
      symptoms at the popliteal fossa and clinical examination of the popliteal fossa
      could not accurately detect BC. US examination of the popliteal fossa should be
      performed to detect BCs and this may recover the diagnosis.

PMID- 24576277
TI  - Protracted febrile myalgia in an afebrile child with familial Mediterranean
      fever.

PMID- 24576278
TI  - Neurosarcoidosis mimicking multiple sclerosis successfully treated with
      methotrexate and adalimumab.

PMID- 24576279
TI  - AL amyloid arthropathy and cardiomyopathy presenting with progressive symmetrical
      fixed flexion deformities and new onset congestive heart failure.

PMID- 24576280
TI  - Alopecia areata in a patient with psoriatic arthritis and Crohn's disease
      receiving etanercept.

PMID- 24576281
TI  - Sonographic evidence of impingement mechanism in a patient with patellar tendon
      rupture after total knee replacement.

PMID- 24576282
TI  - Histiocytic necrotizing lymphadenitis (Kikuchi-Fujimoto disease) preceding
      tuberculous pleurisy.

PMID- 24576283
TI  - Is iontophoresis really an effective modality for the treatment of dactylitis?

PMID- 24576284
TI  - Candida glabrata vertebral osteomyelitis in an immunosuppressed patient.

PMID- 24576286
TI  - "I don't want to be a guinea pig": recruiting older African Americans.

PMID- 24576285
TI  - Localisation and quantification of alkali-labile sites in human spermatozoa by
      DNA breakage detection-fluorescence in situ hybridisation.
AB  - The localisation and quantification of constitutive alkali-labile sites (ALSs)
      were investigated using a protocol of DNA breakage detection plus fluorescence in
      situ hybridisation (DBD-FISH) and alkaline single-cell gel electrophoresis (SCGE
      or comet assay), in spermatozoa of infertile and fertile men. Semen samples from
      10 normozoospermic patients undergoing infertility treatment and 10 fertile men
      were included in this study. ALSs were localised and quantified by DBD-FISH. The
      region most sensitive to alkali treatment in human spermatozoa was located in the
      basal region of the head. ALSs were more frequent in spermatozoa of infertile men
      than in those of fertile men. These results were confirmed by SCGE comet assays.
      In conclusion, the most intense localisation of hybridisation signals in human
      spermatozoa, representing the highest density of constitutive ALSs, was not
      randomly distributed and was predominantly located in the base of the head.
      Moreover, infertile men presented with an increase in ALS frequency. Further
      studies are necessary to determine the association between ALS, sperm chromatin
      organisation and infertility. 

PMID- 24576287
TI  - Update on endnotes' "Alice".

PMID- 24576291
TI  - Structures and solution conformational dynamics of stylissamides G and H from the
      Bahamian sponge Stylissa caribica.
AB  - Two new peptides, stylissamides G and H, were isolated from extracts of a sample
      of Stylissa caribica collected in deep waters of the Caribbean Sea. A single
      sample of S. caribica among a collection of 10 samples that were examined by LC
      MS appeared to be a different chemotype from the others in that it lacked the
      familiar pyrrole-2-aminoimidazole alkaloids, stevensine and oroidin, and
      contained peptides of the stylissamide class. The structures of the title
      compounds were solved by integrated analysis of the MS and NMR spectra and
      chemical degradation. The solution conformation of stylissamide G was briefly
      examined by electronic circular dichroism and temperature-dependent (1)H NMR
      chemical shifts of amide NH signals, which supported a conformationally rigid
      macrocycle. 

PMID- 24576292
TI  - Which cut-off value of serum anti-Mullerian hormone level can predict poor
      ovarian reserve, poor ovarian response to stimulation and in vitro fertilization
      success? A prospective data analysis.
AB  - The aim of our study is to demonstrate which cut-off value of serum anti
      Mullerian hormone (AMH) level can predict poor ovarian reserve, poor ovarian
      response to stimulation and IVF outcomes. About 311 of 520 women enrolled IVF
      treatment cycle that meets inclusion criteria were recruited for this prospective
      data analysis. Data were collected for: age, duration of infertility, basal FSH
      and AMH level, total dosage of gonadotropins, maximum estradiol levels, duration
      of stimulations, total number of oocytes retrieved and clinical PR. Mean AMH was
      1.76 +/- 1.4 ng/ml and mean age was 33.25 +/- 5.5 years. Clinical PR was 39.8% (n
      = 124). AMH was inversely correlated to total dosage of gonadotropins and age,
      AMH positively had a significant correlation with maximum estradiol levels,
      duration of stimulations and total number of oocytes retrieved. The patients in
      both categories of AMH levels, <=0.5 and <=1 ng/ml responded poorly to ovarian
      stimulation, had significantly higher total dosage of gonadotropins used and FSH
      levels on cycle day 3, lower maximum E2 levels and clinical PR. AMH could be an
      acceptable screening test in prediction of ovarian reserve, response to ovarian
      stimulation and PRs. AMH cut-off value <=1 ng/ml may predict poor ovarian
      reserve, poor ovarian response to stimulation and IVF outcomes.

PMID- 24576293
TI  - Oxidation- and CaMKII-mediated sarcoplasmic reticulum Ca(2+) leak triggers atrial
      fibrillation in aging.
AB  - BACKGROUND: Advanced age is a well-recognized predisposition to atrial
      fibrillation (AF). However, the cellular electrophysiological changes that
      underlie the heightened susceptibility to AF in aged individuals remain poorly
      understood. Sarcoplasmic reticulum (SR) Ca(2+) leak that results from
      posttranslational modification of type 2 ryanodine receptor channels (RyR2) has
      been implicated in arrhythmogenesis. We hypothesize that aging alters atrial
      myocytes Ca(2+) homeostasis and RyR2 function, which create a substrate for AF
      initiation. METHODS AND RESULTS: We examined the susceptibility to AF in aged (24
      months) and young adult (4-5 months) mice using an intraesophageal atrial
      electrical stimulation protocol. Aged mice showed significant higher AF induction
      rate (43.3%, n = 30) than young adults (8.8%, n = 34, P < 0.01). In accordance
      with these in vivo findings, significantly increased diastolic SR Ca(2+) leak and
      arrhythmogenic Ca(2+) activities with reduced SR Ca(2+) content were observed in
      aged atrial myocytes. Western blot showed RyR2 oxidation and phosphorylation at
      Ser2814 (Ca(2+) /calmodulin-dependent protein kinase II [CaMKII] site), but not
      phosphorylation at Ser2808 (protein kinase A [PKA] and CaMKII site), were
      increased in aged atrial myocytes. The selective CaMKII inhibitor (KN-93), as
      well as the antioxidant reagent (DTT) reversed the diastolic Ca(2+) leak and the
      frequency of spontaneous Ca(2+) transients in aged atrial myocytes, whereas PKA
      inhibition with H-89 was ineffective. CONCLUSIONS: Aging increases both the
      oxidation and CaMKII-phosphorylation of RyR2, which result in diastolic SR Ca(2+)
      leak and facilitate AF initiation. These results contribute to the
      electrophysiological remodeling of aged atria and suggest a therapeutic strategy
      for AF treatment in aging.

PMID- 24576294
TI  - Association of mannose binding lectin codon 54 polymorphism with predisposition
      to Henoch-Schonlein purpura in childhood.
AB  - AIM: Immune and inflammatory response activation is a common feature of systemic
      vasculitis. There is a protein called mannose binding lectin (MBL) that was
      reported to play an important role in innate immunity. MBL polymorphisms in the
      MBL gene cause predisposition to infectious and autoimmune diseases. There is no
      study in the literature investigating the association between MBL polymorphisms
      and Henoch-Schonlein purpura (HSP) to date. Therefore, the aim of this study is
      to determine the presence of any association between MBL gene variants and HSP in
      a child population. METHOD: Codon 54 polymorphism in exon 1 of the MBL gene was
      investigated by polymerase chain reaction - restriction fragment length
      polymorphism method in 100 children diagnosed as having HSP and 100 age-matched
      healthy controls. RESULTS: The mutant B allele frequency was not significantly
      higher in the patient group (16%) compared to the control group (14%). AB
      genotype was found to be 28% and 26% in the patient group and healthy control
      group, respectively. AA genotype was found in 70% of the children with HSP and
      73% of the healthy control group. CONCLUSION: These results suggest that codon 54
      polymorphism in the MBL gene may hardly play a role in susceptibility to HSP in
      children, the first time this has been reported in the literature.

PMID- 24576297
TI  - Airway, but not serum or urinary, levels of YKL-40 reflect inflammation in early
      cystic fibrosis lung disease.
AB  - BACKGROUND: Cystic fibrosis (CF) lung disease begins in early life and is
      progressive with the major risk factor being an exaggerated inflammatory
      response. Currently, assessment of neutrophilic inflammation in early cystic
      fibrosis (CF) lung disease relies on bronchoalveolar lavage (BAL). The chitinase
      like protein YKL-40 is raised in sputum and serum of adults with CF. We
      investigated YKL-40 in BAL, serum and urine to determine whether this reflected
      inflammation and infection in young children with CF. METHODS: YKL-40 was
      measured in matched samples of BAL, serum and urine obtained from 36 infants and
      young children with CF participating in an early surveillance program. Levels
      were compared to clinical data and markers of inflammation detected in the lung.
      RESULTS: YKL-40 in BAL correlated with pulmonary infection [beta=1.30 (SE 0.34),
      p < 0.001] and BAL markers of inflammation [macrophage number: r2 = 0.34, p <
      0.001; neutrophil number: r2 = 0.74, p < 0.001; neutrophil elastase: r2 = 0.47, p
      < 0.001; CXCL8: r2 = 0.45, p < 0.001; IL-beta: r2 = 0.62, p < 0.001]. YKL-40 was
      detectable in serum but levels did not correlate with BAL levels in the same
      individuals (r2 = 0.04, p = 0.14) or with inflammatory markers. YKL-40 was below
      the limit of detection in urine (30 pg/ml). CONCLUSIONS: This study demonstrates
      that levels of the chitinase-like protein YKL-40 reflect airway inflammation and
      infection in early CF lung disease. The lack of increased YKL-40 in serum in the
      absence of systemic inflammation limits the benefit of this potential biomarker
      in early disease.

PMID- 24576298
TI  - Quality of life of 1276 elderly patients with prostate cancer, starting treatment
      with a gonadotropin-releasing hormone agonist: results of a French observational
      study.
AB  - This French observational, longitudinal, prospective study described the health
      related quality of life (HRQoL) of elderly men (>=75 years old) with prostate
      cancer after initiating gonadotropin-releasing hormone (GnRH) agonist therapy. At
      baseline and 3-6 months after baseline, European Organisation for Research and
      Treatment of Cancer quality of life questionnaire-core 30 (QLQ-C30) and prostate
      specific (QLQ-PR25) questionnaires were completed by patients. Data from 1276
      patients were analyzed. At baseline, mean (+/-SD) age was 80 (+/-4.1) years,
      29.1% of patients had Gleason scores >=8 and 24.9% had metastases. At baseline,
      increasing age, presence of metastasis and presence of comorbidity had a negative
      impact on QLQ-C30 and QLQ-PR25 scores. At follow-up, improvement in emotional
      functioning (2.8; p < 0.001), social-functioning (1.7; p = 0.011), global HRQoL
      (1.6; p = 0.029), sleep-disturbance (-2.1; p = 0.011), appetite-loss (-4.0; p <
      0.001) and pain (-4.1; p < 0.001) QLQ-C30 scores were observed. In addition,
      there was a worsening in treatment-related symptom (8.6; p < 0.001), sexual
      activity (-5.5; p < 0.001) and sexual-functioning (-22.6; p < 0.001) QLQ-PR25
      scores, and an improvement in urinary symptoms (-3.7; p < 0.001) and incontinence
      aid (-2.9; p = 0.023) QLQ-PR25 scores. This study shows that, apart from the
      expected impact on sexual functioning domains, HRQoL is not adversely affected by
      3-6 months of GnRH agonist therapy in older men with prostate cancer.

PMID- 24576299
TI  - The impact of metabolic syndrome on serum total testosterone level in patients
      with erectile dysfunction.
AB  - OBJECTIVES: To determine the association between metabolic syndrome (MetS) and
      serum testosterone levels (TT) in patients with erectile dysfunction (ED).
      METHODS: This study included 280 ED patients above 40-years-of-age. Participants
      were divided into two groups according to 2005 criteria of International Diabetes
      Federation. The severity of ED was determined according to the International
      Index of Erectile Function-EF (IIEF-EF score; 0-10 severe ED, 11-25 mild to
      moderate ED). The severity of ED, serum TT levels and other MetS components were
      compared between the groups. RESULTS: The mean age of the patients was 55.7 +/-
      8.2 years. One hundred eighteen patients (%42.1) had MetS. Sixty-eight patients
      with MetS (57.6%) and 71 patients without MetS (43.8%) had severe ED (p = 0.031).
      A total of 46 (16.4%) patients had hypogonadism. Hypogonadism was seen more
      prevalent in patients with MetS (22.9% vs. 11.7%, p = 0.013). Logistic regression
      analyses for ED risk factors demonstrated that abnormal FBG increased the
      relative risk of severe ED up to 10.7-fold (p < 0.001) but not presence of
      hypogonadism (p = 0.706). CONCLUSION: Metabolic syndrome was seen in almost half
      of the patients with ED. ED was more severe among MetS patients. Hypogonadism
      alone is a not risk factor for severe ED.

PMID- 24576300
TI  - Spirometric obstruction and tobacco exposure among male Turkish nursing home
      residents.
AB  - Spirometric obstruction is a prevalent problem in older adults and related to
      life-style risk factors. Symptoms related to chronic-obstructive-pulmonary
      disease (COPD) are also prevalent symptoms with diverse etiologies - not limited
      to pulmonary obstruction. Older adults may have unrecognized airway obstruction
      due to functional limitations or symptoms mis-attributed to age/other co
      morbidities. Therefore, spirometric obstruction may clinically be over/under
      diagnosed. Over last few decades, the burden of smoking-related diseases has
      increased in older adults. Additional evidence regarding older adults is
      required. We aimed to study frequency of spirometric obstruction, its over/under
      diagnosis and tobacco exposure in a group of male nursing-home residents. For
      spirometric obstruction diagnosis, two different thresholds [(fixed value: 0.70)
      versus (age-corrected value: 0.65 in residents >65 years of age)] were compared
      for better clinical practice. One hundred and three residents with 71.4 +/- 6.3
      years-of-age included. Spirometric obstruction prevalences were 39.8 and 29.1%
      with fixed and age-corrected FEV1/FVC thresholds, respectively. Age-corrected
      FEV1/FVC threshold underdiagnosed COPD in 1.9% while fixed threshold
      overdiagnosed spirometric obstruction in 8.7%. Active smokers were 64.1%, ex
      smokers 23.3% and non-smokers 12.6%. Our study suggests high prevalences of
      spirometric obstruction and smoking in male nursing-home residents in Turkey. We
      suggest the use of age-corrected FEV1/FVC threshold practicing better than the
      use of fixed FEV1/FVC threshold in this patient group. 

PMID- 24576302
TI  - Involvement of the Wnt-beta-catenin signalling antagonists, sclerostin and
      dickkopf-related protein 1, in chronic periodontitis.
AB  - AIM: The regulation of Wnt-beta-catenin signalling, which is crucial for
      osteoblast differentiation and for bone resorption, is driven by critical
      inhibitors such as sclerostin (SOST) and dickkopf-related protein 1 (DKK1). As
      such, the aim of this study was to evaluate the involvement of SOST and DKK1 in
      human chronic periodontitis. MATERIAL AND METHODS: Gingival biopsies and serum
      were sampled from systemically healthy non-periodontitis (n = 15) and chronic
      periodontitis subjects (n = 15). The mRNA and protein levels of SOST, DKK1 and
      TNF-alpha in periodontal tissues were measured by qPCR and by enzyme-linked
      immunosorbent assay (ELISA) respectively. Serum levels of SOST, DKK1 and TNF
      alpha were assessed by ELISA. RESULTS: The mRNA and protein levels of SOST, DKK1
      and TNF-alpha were significantly increased in the gingival tissues of the chronic
      periodontitis when compared to the non-periodontitis group (p < 0.05). In
      addition, circulating levels of SOST and TNF-alpha, but not DKK1, were higher in
      the periodontitis group than in the non-periodontitis group (p < 0.05).
      CONCLUSION: SOST and DKK1 were upregulated in the periodontal tissues of chronic
      periodontitis subjects, suggesting a possible role of these molecules on
      periodontal tissues.

PMID- 24576301
TI  - Host cell virus entry mediated by Australian bat lyssavirus G envelope
      glycoprotein occurs through a clathrin-mediated endocytic pathway that requires
      actin and Rab5.
AB  - BACKGROUND: Australian bat lyssavirus (ABLV), a rhabdovirus of the genus
      Lyssavirus which circulates in both pteropid fruit bats and insectivorous bats in
      mainland Australia, has caused three fatal human infections, the most recent in
      February 2013, manifested as acute neurological disease indistinguishable from
      clinical rabies. Rhabdoviruses infect host cells through receptor-mediated
      endocytosis and subsequent pH-dependent fusion mediated by their single envelope
      glycoprotein (G), but the specific host factors and pathways involved in ABLV
      entry have not been determined. METHODS: ABLV internalization into HEK293T cells
      was examined using maxGFP-encoding recombinant vesicular stomatitis viruses
      (rVSV) that express ABLV G glycoproteins. A combination of chemical and molecular
      approaches was used to investigate the contribution of different endocytic
      pathways to ABLV entry. Dominant negative Rab GTPases were used to identify the
      endosomal compartment utilized by ABLV to gain entry into the host cell cytosol.
      RESULTS: Here we show that ABLV G-mediated entry into HEK293T cells was
      significantly inhibited by the dynamin-specific inhibitor dynasore,
      chlorpromazine, a drug that blocks clathrin-mediated endocytosis, and the actin
      depolymerizing drug latrunculin B. Over expression of dominant negative mutants
      of Eps15 and Rab5 also significantly reduced ABLV G-mediated entry into HEK293T
      cells. Chemical inhibitors of caveolae-dependent endocytosis and macropinocytosis
      and dominant negative mutants of Rab7 and Rab11 had no effect on ABLV entry.
      CONCLUSIONS: The predominant pathway utilized by ABLV for internalization into
      HEK293T cells is clathrin-and actin-dependent. The requirement of Rab5 for
      productive infection indicates that ABLV G-mediated fusion occurs within the
      early endosome compartment.

PMID- 24576303
TI  - Detection and partial sequencing of Schmallenberg virus in cattle and sheep in
      Turkey.
AB  - To investigate the Schmallenberg virus (SBV) in Turkey, 116 aborted fetuses from
      sheep (60), goats (12), and cattle (44) collected from different regions of
      Turkey were analyzed by real-time PCR. SBV RNA was detected in aborted fetuses of
      sheep and cattle from the Marmara region, which borders the European Union. In
      contrast, samples were found to be negative for Akabane virus by real-time PCR.
      The partial sequencing of the S gene of SBV confirmed the first detection of SBV
      in Turkey.

PMID- 24576304
TI  - Hyoscine-N-butylbromide premedication on cardiovascular variables of horses
      sedated with medetomidine.
AB  - OBJECTIVE: To evaluate the effects of intravenous (IV) or intramuscular (IM)
      hyoscine premedication on physiologic variables following IV administration of
      medetomidine in horses. STUDY DESIGN: Randomized, crossover experimental study.
      ANIMALS: Eight healthy crossbred horses weighing 330 +/- 39 kg and aged 7 +/- 4
      years. METHODS: Baseline measurements of heart rate (HR), cardiac index (CI),
      respiratory rate, systemic vascular resistance (SVR), percentage of patients with
      second degree atrioventricular (2(o) AV) block, mean arterial pressure (MAP), pH,
      and arterial partial pressures of carbon dioxide (PaCO2 ) and oxygen (PaO2 ) were
      obtained 5 minutes before administration of IV hyoscine (0.14 mg kg(-1) ; group
      HIV), IM hyoscine (0.3 mg kg(-1) ; group HIM), or an equal volume of physiologic
      saline IV (group C). Five minutes later, medetomidine (7.5 MUg kg(-1) ) was
      administered IV and measurements were recorded at various time points for 130
      minutes. RESULTS: Medetomidine induced bradycardia, 2(o) AV blocks and increased
      SVR immediately after administration, without significant changes in CI or MAP in
      C. Hyoscine administration induced tachycardia and hypertension, and decreased
      the percentage of 2(o) AV blocks induced by medetomidine. Peak HR and MAP were
      higher in HIV than HIM at 88 +/- 18 beats minute(-1) and 241 +/- 37 mmHg versus
      65 +/- 16 beats minute(-1) and 192 +/- 38 mmHg, respectively. CI was increased
      significantly in HIV (p <= 0.05). Respiratory rate decreased significantly in all
      groups during the recording period. pH, PaCO2 and PaO2 were not significantly
      changed by administration of medetomidine with or without hyoscine. CONCLUSION
      AND CLINICAL RELEVANCE: Hyoscine administered IV or IM before medetomidine in
      horses resulted in tachycardia and hypertension under the conditions of this
      study. The significance of these changes, and responses to other dose rates,
      requires further investigation.

PMID- 24576305
TI  - Isolation and sequencing of swine carbonic anhydrase VI, an enzyme expressed in
      the swine kidney.
AB  - BACKGROUND: Carbonic anhydrase VI (CA-VI) is produced by the salivary gland and
      is secreted into the saliva. Although CA-VI is found in the epithelial cells of
      distal straight tubule of swine kidneys, the exact function of CA-VI in the
      kidneys remains unclear. RESULTS: CA-VI was located in the epithelial cells of
      distal straight tubule of swine kidneys.A full-length cDNA clone of CA-VI was
      generated from the swine parotid gland by reverse transcription polymerase chain
      reaction, using degenerate primers designed based on conserved regions of the
      same locus in human and bovine tissues. The cDNA sequence was 1348 base pairs
      long and was predicted to encode a 317 amino acid polypeptide with a putative
      signal peptide of 17 amino acids. The deduced amino acid sequence of mature CA-VI
      was most similar (77.4%) to that of human CA-VI. CA-VI expression was confirmed
      in both normal and nephritic kidneys, as well as parotid. As the primers used in
      this study spanned two exons, the influence of genomic DNA was not detected. The
      expression of CA-VI was demonstrated in both normal and nephritic kidneys, and
      mRNA of CA-VI in the normal kidneys which was the normalised to an endogenous
      beta-actin was 0.098 +/- 0.047, while it was significantly lower in the diseased
      kidneys (0.012 +/- 0.007). The level of CA-VI mRNA in normal kidneys was 19-fold
      lower than that of the parotid gland (1.887). CONCLUSIONS: The localisation of CA
      VI indicates that it may play a specialised role in the kidney.

PMID- 24576307
TI  - An exploratory study of how sports and recreation industry personnel perceive the
      barriers and facilitators of physical activity in children with disability.
AB  - PURPOSE: To explore the perceived barriers and facilitators to participation in
      physical activity among children with disability in physical activity and
      community sports from the perspective of sports and recreation industry
      personnel. METHOD: A convenient sample of 24 participants was recruited from
      delegates attending a symposium on physical activity for organisations in the
      sport and recreation sector in Victoria, Australia. The participants completed a
      brief questionnaire. Data were analysed by content analysis using an inductive
      approach. RESULTS: The participants reported 25 facilitators and 20 barriers to
      participation for children with disability. The top five reported facilitators
      were: welcoming providers, support and encouragement from parents or others,
      inclusive providers, adaptable approaches and accessibility of facilities. The
      top five reported barriers were: inaccessible facilities, non-inclusive
      providers, transport, lack of relevant opportunities and cost. CONCLUSIONS:
      Sports industry personnel share a similar perspective to families of potential
      barriers and facilitators to engagement by children with disability in physical
      activity and community sports. Policy change was not considered as a facilitator
      of physical activity, even though four of the top five facilitators identified
      could be implemented through local policy change. Implications for Rehabilitation
      There are multiple factors that interact with each other which influence the
      participation by children with disability in physical activity and community
      sports. The sports and recreation industry should consider policy change as a
      relevant way to facilitate participation by children with disability in physical
      activity. More professional development and disability engagement opportunities
      for sports and recreation industry personnel may help address some of the
      barriers to participation for children with disability experience.

PMID- 24576306
TI  - Perceived outcomes of web-based modules designed to enhance athletic trainers'
      knowledge of evidence-based practice.
AB  - CONTEXT: The release of evidence-based practice (EBP) Web-based learning modules
      to the membership of the National Athletic Trainers' Association has provided
      athletic trainers (ATs) the opportunity to enhance their knowledge of the various
      EBP concepts. Whereas increasing the knowledge of EBP among ATs is important,
      assessing whether this newfound knowledge is being translated into clinical
      practice and didactic education is crucial. OBJECTIVE: To explore the
      effectiveness of an educational intervention regarding EBP on the didactic
      instruction patterns of athletic training educators and the clinical practice
      behaviors of clinicians. DESIGN: Qualitative study. SETTING: Individual telephone
      interviews. PATIENTS OR OTHER PARTICIPANTS: A total of 25 ATs (12 educators, 13
      clinicians; experience as an AT = 16.00 +/- 9.41 years) were interviewed. DATA
      COLLECTION AND ANALYSIS: We conducted 1 individual telephone interview with each
      participant. After transcription, the data were analyzed and coded into common
      themes and categories. Triangulation of the data occurred via the use of multiple
      researchers and member checking to confirm the accuracy of the data. RESULTS:
      Participants perceived the EBP Web-based modules to produce numerous outcomes
      regarding education and clinical practice. These outcomes included perceived
      knowledge gain among participants, an increase in the importance and scope of
      EBP, a positive effect on educators' didactic instruction patterns and on
      instilling value and practice of EBP among students, and an enhanced ability
      among clinicians to implement EBP within clinical practice. However, some
      clinicians reported the Web-based modules had no current effect on clinical
      practice. CONCLUSIONS: Although the EBP Web-based modules were successful at
      enhancing knowledge among ATs, translation of knowledge into the classroom and
      clinical practice remains limited. Researchers should aim to identify effective
      strategies to help ATs implement EBP concepts into didactic education and
      clinical practice.

PMID- 24576308
TI  - "This is not just a little accident": a qualitative understanding of paediatric
      burns from the perspective of parents.
AB  - PURPOSE: To describe the experiences of parents of children admitted to hospital
      for a burn. METHODS: In-depth interviews were conducted with 21 parents (14
      mothers and seven fathers) of children who had sustained a burn requiring
      hospitalisation. Face-to-face interviews were conducted six months post-burn, in
      rural, remote and metropolitan areas. The interview guide explored the overall
      experience of parents and included probing questions exploring the perceptions,
      thoughts and feelings of participants. Interviews were digitally recorded and
      transcribed verbatim. Transcripts were analysed according to the seven-step
      Coliazzi method. Relationships between themes were explored to identify core
      concepts. RESULTS: Analysis of interview transcripts revealed three phases that
      describe the parents' journey: experiencing the accident, the in-patient phase
      and the return to community. Within these phases, themes were identified. Themes
      represented subthemes of stressors, behavioural and emotional responses and
      coping factors. CONCLUSION: Findings from this research will allow health
      professionals to optimise a holistic clinical service from a consumer's
      perspective at all stages of the burn journey. These research conclusions could
      be used for the development of protocols to underpin a comprehensive information
      and social support management plan for families that would complement and support
      the surgical, medical and therapeutic treatment plan, providing direction for
      comprehensive service delivery. Implications for Rehabilitation Health
      professionals should optimise a holistic clinical service from a consumer's
      perspective taking into consideration all stages of the burn journey. Therapeutic
      supports are required to target each phase of the burn journey and address
      changes in coping strategies and behavioural responses. There is a need for the
      development of protocols to underpin a comprehensive information and social
      support management plan for families that will complement and support the
      surgical and medical treatment plan.

PMID- 24576309
TI  - Free volume model for the unexpected effect of C2-methylation on the properties
      of imidazolium ionic liquids.
AB  - For 1-alkyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imides and their
      cationic C2-methylated isomers, that is, [C(n)MIm]NTf2 and [C(n-1)DMIm]NTf2 (n =
      3-8), the latter always has much higher viscosities (~1.66 times at 25  degrees
      C) than the former. This finding is unexpected and contrary to the loss of the
      predominant hydrogen bonding between the cation and anion, caused by the C2
      methylation in the imidazolium ionic liquids. In the present study, we propose a
      free volume model to explain this mysterious phenomenon. For the isomeric pairs,
      [C(n-1)DMIm]NTf2 was found to possess less unoccupied (free) volume than
      [C(n)MIm]NTf2 by ~4.5 mL mol(-1) determined by both Furth's surface tension and
      molar volume methods, and the free volume difference can be quantitatively
      correlated with the C2-methylation effect on viscosity. Generally, the less free
      volume in [C(n-1)DMIm]NTf2 relative to [C(n)MIm]NTf2 reduces the number of the
      hole carriers for molecular transport with a resulting increase in viscosity.
      Besides, the free volume model can also be applied to account for the C2
      methylation effect on other properties, such as conductivity, surface tension,
      density, and refractive index.

PMID- 24576310
TI  - p,p'-DDE induces apoptosis through the modulation of tumor necrosis factor alpha
      in PC12 cells.
AB  - p,p'-DDE, the main metabolite of DDT, is notorious for its persistent and
      bioaccumulation. It has detrimental effects on the nervous system, while the
      mechanism is unclear. We sought to investigate the mechanism of p,p'-DDE-induced
      neurocytic apoptosis in PC12 cells by cytoflow and screen the potential target
      gene by microarray and ELISA. Co-incubation with antagonist and SiRNA were
      applied to confirm the effect of the selected molecular. Results were also
      confirmed in zebrafish embryo. Results showed that p,p'-DDE induced apoptosis in
      PC12 cells at a concentration of >=2 * 10(-5) mol/L. Microarray results indicate
      that the TNF family plays a key role in p,p'-DDE-induced apoptosis among 84
      apoptotic genes. In particular, the protein level of TNFalpha increased 4-fold.
      When incubated with TNFalpha antibody (infliximab), the number of apoptotic cells
      attenuated by 50%, and both activities of caspases 8 and 9 decreased. SiRNA
      silencing of TNFalpha showed similar trends. Furthermore, p,p'-DDE induced
      neuronal apoptosis in zebrafish embryos in a dose-dependent manner.This effect
      was partially reversed by infliximab, too. Overall, the present study herein
      indicated that the TNFalpha signaling pathway is involved in p,p'-DDE-induced
      neurocyte apoptosis. These data could be expanded to other cases of OCP-induced
      apoptosis and would support the need for scientific intervention to address the
      neurotoxicity of these chemicals.

PMID- 24576311
TI  - Sunitinib in metastatic renal cell carcinoma: an ethnic Asian subpopulation
      analysis for safety and efficacy.
AB  - AIMS: We evaluated and compared the safety and efficacy of sunitinib in Asian and
      non-Asian patients with metastatic renal cell carcinoma enrolled in a previously
      reported global expanded access program. METHODS: Previously treated and
      treatment-naive patients received open-label sunitinib at a starting dose of 50
      mg/day for 4 weeks, followed by 2 weeks off treatment, in repeated 6-week cycles.
      Safety was assessed regularly, tumor measurements were performed per local
      practice, and survival data collected where possible. RESULTS: Data were
      available for 212 Asian patients from Asian sites (Asian-A), 113 Asian patients
      from non-Asian sites (Asian-O) and 4046 non-Asian patients. The most common grade
      3/4 treatment-related adverse events were neutropenia, thrombocytopenia, hand
      foot syndrome, diarrhea, asthenia and fatigue. The incidence of many adverse
      events was greater in Asian-A than in Asian-O or non-Asian patients. Sunitinib
      efficacy was comparable between Asian and non-Asian patients, with an objective
      response rate of 18% versus 14%; median progression-free survival of 8.7 versus
      10.9 months; and overall survival of 18.9 versus 18.4 months, respectively.
      CONCLUSIONS: Sunitinib demonstrated tolerable safety and similar efficacy in
      Asian and non-Asian patients. Geographic differences in the reported frequency of
      specific adverse events were noted across Asian patients.

PMID- 24576312
TI  - Assessment of the normal and pathological alignment of the elbow in children
      using the trochleocapitellar index.
AB  - BACKGROUND: The current research is a retrospective study that involves the
      description of a new trochleocapitellar index (TCI), on basis of anteroposterior
      (AP) radiographs of normal and fractured paediatric elbows. This index may be
      useful in assessing the alignment of the elbow with a supracondylar fracture.
      METHODS: The index was evaluated to define its normal and pathological range in
      children between the ages of 1-13 years. A total of 212 elbows in 141 children
      were radiographically evaluated. 70 children without fracture elbows were
      evaluated by radiographs taken at the time of trauma. 35 children with unilateral
      fractures that healed in a normal alignment were compared to 33 patients that had
      a mal-union and three patients with bilateral elbow fractures. The patients were
      radiographically assessed at the time of fracture as well as after fracture
      healing as part of a routine clinical assessment. Treatment included observation,
      cast or internal fixation as needed. RESULTS: The current study establishes that
      the normal range of the TCI was 0.25-0.8. The average TCI is 0.45. The lower
      range correlates with a valgus alignment of the elbow while the higher range
      indicates a neutral alignment. The TCI in fractured elbows that have healed in a
      clinically normal alignment is different than the contra-lateral elbow's TCI.
      This might indicate a sub-clinical remaining deformity. CONCLUSIONS: In current
      practice, paediatric patients with elbow trauma, often undergo bilateral
      radiographs during emergency room visits. The TCI has high negative and positive
      predictive values and might be superior to direct angle measurement that is
      currently in use. The use of the TCI measurement is expected to reduce exposure
      to irradiation in elbow trauma patients as bilateral comparative films appear to
      be superfluous when this measurement is used.

PMID- 24576313
TI  - Managing driving issues after an acquired brain injury: strategies used by health
      professionals.
AB  - BACKGROUND/AIM: The ability to drive safely can be affected by an acquired brain
      injury. Following acquired brain injury, clients may experience driving
      disruptions, formal assessment, return to driving or permanent cessation. Health
      professionals may be involved in formal driving or component skills' assessment
      and rehabilitation, or interventions for continued community participation.
      Meeting the needs of clients related to driving remains a challenging area of
      clinical practice. The aim of this study was to investigate how driving issues
      are currently managed by acquired brain injury rehabilitation teams. METHOD: This
      study utilised a qualitative phenomenological approach to gain insight into the
      approaches undertaken by four rehabilitation teams working with clients post
      acquired brain injury. Semi-structured, audiotaped interviews were conducted with
      25 participants who had identified driving as part of their role. RESULTS: Health
      professional participants described three major areas of clinical focus,
      describing strategies and challenges associated with each. These were as follows:
      'Integrating driving goals into rehabilitation' which involved optimising timing
      and acknowledging the clients' focus on driving while enhancing driving and
      rehabilitation outcomes; 'Managing emotional responses' which required protecting
      therapeutic relationships and providing information, as well as responding to
      more extreme responses; and finally 'Managing unlicensed driving and meeting long
      term needs', which participants identified as the most challenging aspect.
      Strategies involved using set procedures, building on knowledge of the client,
      supporting the family and exploring alternatives. CONCLUSION: The teams described
      a range of strategies used to address the challenges related to driving and
      driving cessation which can be applied to successfully manage this issue in
      acquired brain injury rehabilitation.

PMID- 24576314
TI  - Poorer sustained attention in bipolar I than bipolar II disorder.
AB  - BACKGROUND: Nearly all information processing during cognitive processing takes
      place during periods of sustained attention. Sustained attention deficit is among
      the most commonly reported impairments in bipolar disorder (BP). The majority of
      previous studies have only focused on bipolar I disorder (BP I), owing to
      underdiagnosis or misdiagnosis of bipolar II disorder (BP II). With the
      refinement of the bipolar spectrum paradigm, the goal of this study was to
      compare the sustained attention of interepisode patients with BP I to those with
      BP II. METHODS: In all, 51 interepisode BP patients (22 with BP I and 29 with BP
      II) and 20 healthy controls participated in this study. The severity of
      psychiatric symptoms was assessed by the 17-item Hamilton Depression Rating Scale
      and the Young Mania Rating Scale. All participants undertook Conners' Continuous
      Performance Test II (CPT-II) to evaluate sustained attention. RESULTS: After
      controlling for the severity of symptoms, age and years of education, BP I
      patients had a significantly longer reaction times (F(2,68) = 7.648, P = 0.001),
      worse detectability (d') values (F(2,68) = 6.313, P = 0.003) and more commission
      errors (F(2,68) = 6.182, P = 0.004) than BP II patients and healthy controls. BP
      II patients and controls scored significantly higher than BP I patients for d' (F
      = 6.313, P = 0.003). No significant difference was found among the three groups
      in omission errors and no significant correlations were observed between CPT-II
      performance and clinical characteristics in the three groups. CONCLUSIONS: These
      findings suggested that impairments in sustained attention might be more
      representative of BP I than BP II after controlling for the severity of symptoms,
      age, years of education and reaction time on the attentional test. A longitudinal
      follow-up study design with a larger sample size might be needed to provide more
      information on chronological sustained attention deficit in BP patients, and to
      illustrate clearer differentiations between the three groups.

PMID- 24576316
TI  - Characterisation of tramadol, morphine and tapentadol in an acute pain model in
      Beagle dogs.
AB  - OBJECTIVE: To evaluate the analgesic potential of the centrally acting analgesics
      tramadol, morphine and the novel analgesic tapentadol in a pre-clinical research
      model of acute nociceptive pain, the tail-flick model in dogs. STUDY DESIGN:
      Prospective part-randomized pre-clinical research trial. ANIMALS: Fifteen male
      Beagle dogs (HsdCpb:DOBE), aged 12-15 months. METHODS: On different occasions
      separated by at least 1 week, dogs received intravenous (IV) administrations of
      tramadol (6.81, 10.0 mg kg(-1) ), tapentadol (2.15, 4.64, 6.81 mg kg(-1) ) or
      morphine (0.464, 0.681, 1.0 mg kg(-1) ) with subsequent measurement of tail
      withdrawal latencies from a thermal stimulus (for each treatment n = 5). Blood
      samples were collected immediately after the pharmacodynamic measurements of
      tramadol to determine pharmacokinetics and the active metabolite O
      demethyltramadol (M1). RESULTS: Tapentadol and morphine induced dose-dependent
      antinociception with ED50-values of 4.3 mg kg(-1) and 0.71 mg kg(-1) ,
      respectively. In contrast, tramadol did not induce antinociception at any dose
      tested. Measurements of the serum levels of tramadol and the M1 metabolite
      revealed only marginal amounts of the M1 metabolite, which explains the absence
      of the antinociceptive effect of tramadol in this experimental pain model in
      dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Different breeds of dogs might not or
      only poorly respond to treatment with tramadol due to low metabolism of the drug.
      Tapentadol and morphine which act directly on MU-opioid receptors without the
      need for metabolic activation are demonstrated to induce potent antinociception
      in the experimental model used and should also provide a reliable pain management
      in the clinical situation. The non-opioid mechanisms of tramadol do not provide
      antinociception in this experimental setting. This contrasts to many clinical
      situations described in the literature, where tramadol appears to provide useful
      analgesia in dogs for post-operative pain relief and in more chronically pain
      states.

PMID- 24576315
TI  - An evaluation of the infection control potential of a UV clinical podiatry unit.
AB  - BACKGROUND: Infection control is a key issue in podiatry as it is in all forms of
      clinical practice. Airborne contamination may be particularly important in
      podiatry due to the generation of particulates during treatment. Consequently,
      technologies that prevent contamination in podiatry settings may have a useful
      role. The aims of this investigation were twofold, firstly to determine the
      ability of a UV cabinet to protect instruments from airborne contamination and
      secondly to determine its ability to remove microbes from contaminated surfaces
      and instruments. METHOD: A UV instrument cabinet was installed in a University
      podiatry suite. Impact samplers and standard microbiological techniques were used
      to determine the nature and extent of microbial airborne contamination. Sterile
      filters were used to determine the ability of the UV cabinet to protect exposed
      surfaces. Artificially contaminated instruments were used to determine the
      ability of the cabinet to remove microbial contamination. RESULTS: Airborne
      bacterial contamination was dominated by Gram positive cocci including
      Staphylococcus aureus. Airborne fungal levels were much lower than those observed
      for bacteria. The UV cabinet significantly reduced (p < 0.05) the observed levels
      of airborne contamination. When challenged with contaminated instruments the
      cabinet was able to reduce microbial levels by between 60% to 100% with more
      complex instruments e.g. clippers, remaining contaminated. CONCLUSIONS: Bacterial
      airborne contamination is a potential infection risk in podiatry settings due to
      the presence of S. aureus. The use of a UV instrument cabinet can reduce the risk
      of contamination by airborne microbes. The UV cabinet tested was unable to
      decontaminate instruments and as such could pose an infection risk if misused.

PMID- 24576317
TI  - Nile blue can photosensitize DNA damage through electron transfer.
AB  - The mechanism of DNA damage photosensitized by Nile blue (NB) was studied using
      (32)P-5'-end-labeled DNA fragments. NB bound to the DNA strand was possibly
      intercalated through an electrostatic interaction. Photoirradiated NB caused DNA
      cleavage at guanine residues when the DNA fragments were treated with piperidine.
      Consecutive guanines, the underlined G in 5'-GG and 5'-GGG, were selectively
      damaged through photoinduced electron transfer. The fluorescence lifetime of NB
      was decreased by guanine-containing DNA sequence, supporting this mechanism.
      Single guanines were also slightly damaged by photoexcited NB, and DNA
      photodamage by NB was slightly enhanced in D2O. These results suggest that the
      singlet oxygen mechanism also partly contributes to DNA photodamage by NB. DNA
      damage photosensitized by NB via electron transfer may be an important mechanism
      in medicinal applications of photosensitizers, such as photodynamic therapy in
      low oxygen.

PMID- 24576318
TI  - Clinical utility of urinary soluble Fas in screening for bladder cancer.
AB  - AIM: Early diagnosis of carcinoma of urinary bladder remains a challenge. Urine
      cytology, as an adjunct to cystoscopy, is less sensitive for low-grade tumors.
      Soluble Fas (sFas), a cell-surface receptor and member of the tumor necrosis
      factor superfamily, is frequently expressed in urinary bladder carcinoma. The
      objective of this study was to investigate the urinary sFas for diagnosis of
      transitional cell carcinoma (TCC) of urinary bladder. METHODS: We examined
      urinary sFas concentration in 74 controls and 117 cases of TCC, both primary and
      recurrent disease, by using enzyme-linked immunosorbent assay and compared it
      with urinary cytology. RESULT: Urinary sFas concentration was found to be
      significantly higher in the patient as compared to control group (P < 0.05). An
      optimal cutoff value of 174.0 pg/mL was proposed. The urinary sFas level was
      found to have an approximate sensitivity and specificity of 88.03% and 89.19% (P
      < 0.001), whereas urine cytology had sensitivity of 66.67% and specificity of
      95.95%. sFas had better sensitivity in higher grade and both primary and
      recurrent cases of urinary bladder cancer in comparison with cytology. Out of 15
      node positive bladder cancer cases, 13 had high urinary sFas levels, whereas 12
      were urinary cytology positive for malignancy. CONCLUSION: Urinary sFas can be
      used as a non-invasive diagnostic biomarker for TCC of urinary bladder, both for
      primary and recurrent disease.

PMID- 24576319
TI  - Proteomic identification of fucosylated haptoglobin alpha isoforms in ascitic
      fluids and its localization in ovarian carcinoma tissues from Mexican patients.
AB  - BACKGROUND: Ovarian cancer is the most lethal gynecologic disease due to delayed
      diagnosis, and ascites production is a characteristic of patients in advanced
      stages. The aim of this study was to perform the proteomic analysis of ascitic
      fluids of Mexican patients with ovarian carcinoma, in order to detect proteins
      with a differential expression pattern in the continuing search to identify
      biomarkers for this disease. METHODS: Samples were collected from 50 patients
      from the Instituto Nacional de Cancerologia of Mexico under informed consent and
      with approval of the bioethics and scientific committees. After elimination of
      abundant proteins (Albumin/IgGs) samples were processed for 2D electrophoresis
      and further protein identification by Mass Spectrometry (MALDI-TOF). Molecules of
      interest were followed by western blot and lectin binding assays, and their
      tissue location by histo-immunofluorescence and confocal analysis. RESULTS AND
      DISCUSSION: An area with a differential expression pattern among samples was
      located in the 2D gels. Identified proteins were 6 alpha 1 isoforms and 1 alpha 2
      isoform of Haptoglobin, and 2 isoforms of Transthyretin. While Transthyretin
      isoforms were constitutively expressed in all samples, clear differences in the
      expression pattern of Haptoglobin alpha isoforms were found. Moreover, increased
      levels of fucosylation of Haptoglobin alpha isoforms analyzed in 40 samples by
      Aleuria aurantia lectin binding by 1D overlay assay showed a positive correlation
      with advanced stages of the disease. Tissue detection of Haptoglobin and its
      fucosylated form, by histo-immunofluorescence in biopsies of ovarian cancer, also
      showed a correlation with ovarian cancer progression. Moreover, results show that
      fucosylated Haptoglobin is produced by tumor cells. CONCLUSIONS: Increased
      numbers of highly fucosylated Haptoglobin alpha isoforms in ascitic fluids and
      the presence of fucosylated Haptoglobin in tumor tissues of ovarian cancer
      Mexican patients associated with advanced stages of the disease, reinforce the
      potential of fucosylated Haptoglobin alpha isoforms to be characterized as
      biomarkers for disease progression.

PMID- 24576320
TI  - Multiplexed immunoglobulin E sensitization in relation to exhaled nitric oxide in
      a population sample of children.
AB  - This study investigated the relationship between the specific immunoglobulin E
      (IgE) profile for 40 allergens using a novel microarray technique (BioIC) and
      fraction of exhaled nitric oxide (FeNO) in a population sample of 1321 children.
      Significant positive associations were found between FeNO and sensitization to
      mites (P < 0.001), animals (P = 0.001), cockroaches (P < 0.001), and foods (P =
      0.042), and furthermore, between FeNO and the number of sensitizations (all P <
      0.05) or the sum of specific IgE (all P <= 0.01) against the aforementioned
      allergen categories. Specifically, sensitization to the following allergens was
      significantly related to higher FeNO: Dermatophagoides pteronyssinus,
      Dermatophagoides farina, Blomia tropicalis, cat, German cockroach, Oriental
      cockroach, codfish, crab, shrimp, and cheese (all P <= 0.01). In conclusion, IgE
      sensitization to mites, pets, cockroaches, seafood, and cheese, respectively, is
      significantly associated with elevated FeNO levels in a dose-dependent fashion in
      children. Our results provide new evidence that sensitization to certain food
      allergens may contribute to prompt inflammation in the airways. 

PMID- 24576322
TI  - Use of REP- and ERIC-PCR to reveal genetic heterogeneity of Vibrio cholerae from
      edible ice in Jakarta, Indonesia.
AB  - BACKGROUND: Vibrio cholerae is the causative organism of waterborne disease,
      cholera. V. cholerae has caused many epidemics and pandemics of cholera for many
      years. In this study, V. cholerae recovered from edible ice were investigated for
      their genetic diversity using Enterobacterial Repetitive Intergenic Consensus
      (ERIC) PCR and Repetitive Extragenic Palindromic (REP) PCR. Isolation was done
      using selective medium and the presumptive isolates were confirmed through
      biochemical and serological assays. RESULTS: Seventy-five isolates of V. cholerae
      were recovered from ice samples collected from different locations of Jakarta.
      Specifically, 19 of them were identified as O1 serotype, 16 were Ogawa, 3
      isolates were Inaba and the remaining isolates were non-O1. The fingerprinting
      profiles of V.cholerae isolated from ice samples were very diverse. CONCLUSION:
      This result showed that the ERIC sequence is more informative and discriminative
      than REP sequence for analysis of V. cholerae diversity.

PMID- 24576321
TI  - What is the ideal dose and power output of low-level laser therapy (810 nm) on
      muscle performance and post-exercise recovery? Study protocol for a double-blind,
      randomized, placebo-controlled trial.
AB  - BACKGROUND: Recent studies involving phototherapy applied prior to exercise have
      demonstrated positive results regarding the attenuation of muscle fatigue and the
      expression of biochemical markers associated with recovery. However, a number of
      factors remain unknown, such as the ideal dose and application parameters,
      mechanisms of action and long-term effects on muscle recovery. The aims of the
      proposed project are to evaluate the long-term effects of low-level laser therapy
      on post-exercise musculoskeletal recovery and identify the best dose
      andapplication power/irradiation time. DESIGN AND METHODS: A double-blind,
      randomized, placebo-controlled clinical trial with be conducted. After fulfilling
      the eligibility criteria, 28 high-performance athletes will be allocated to four
      groups of seven volunteers each. In phase 1, the laser power will be 200 mW and
      different doses will be tested: Group A (2 J), Group B (6 J), Group C (10 J) and
      Group D (0 J). In phase 2, the best dose obtained in phase 1 will be used with
      the same distribution of the volunteers, but with different powers: Group A (100
      mW), Group B (200 mW), Group C (400 mW) and Group D (0 mW). The isokinetic test
      will be performed based on maximum voluntary contraction prior to the application
      of the laser and after the eccentric contraction protocol, which will also be
      performed using the isokinetic dynamometer. The following variables related to
      physical performance will be analyzed: peak torque/maximum voluntary contraction,
      delayed onset muscle soreness (algometer), biochemical markers of muscle damage,
      inflammation and oxidative stress. DISCUSSION: Our intention, is to determine
      optimal laser therapy application parameters capable of slowing down the
      physiological muscle fatigue process, reducing injuries or micro-injuries in
      skeletal muscle stemming from physical exertion and accelerating post-exercise
      muscle recovery. We believe that, unlike drug therapy, LLLT has a biphasic dose
      response pattern. TRIAL REGISTRATION: The protocol for this study is registered
      with the Protocol Registry System, ClinicalTrials.gov identifier NCT01844271.

PMID- 24576324
TI  - Recurrent lymphocytic myocarditis in a young male with ulcerative colitis.
AB  - Awareness of myocarditis in association with inflammatory bowel diseases is
      crucial as it bears a rare but serious risk for mortality. This report describes
      the case of a young Caucasian male, whose heart biopsy was tested negative for
      giant cells and bacterial or viral genomes or proteins. He was experiencing
      severe lymphocytic myocarditis (other than mesalamine-induced) along with
      cardiogenic shock during ulcerative colitis exacerbation. This is an extremely
      rare, if not unique, clinical constellation. We chose to study the epidemiologic
      grounds and all major aspects of differential pathogenesis and treatment of this
      serious health problem. 

PMID- 24576326
TI  - Magnetotransport in an aluminum thin film on a GaAs substrate grown by molecular
      beam epitaxy.
AB  - Magnetotransport measurements are performed on an aluminum thin film grown on a
      GaAs substrate. A crossover from electron- to hole-dominant transport can be
      inferred from both longitudinal resistivity and Hall resistivity with increasing
      the perpendicular magnetic field B. Also, phenomena of localization effects can
      be seen at low B. By analyzing the zero-field resistivity as a function of
      temperature T, we show the importance of surface scattering in such a nanoscale
      film. 

PMID- 24576325
TI  - Prevalence of influenza A viruses in livestock and free-living waterfowl in
      Uganda.
AB  - BACKGROUND: Avian influenza viruses may cause severe disease in a variety of
      domestic animal species worldwide, with high mortality in chickens and turkeys.
      To reduce the information gap about prevalence of these viruses in animals in
      Uganda, this study was undertaken. RESULTS: Influenza A virus prevalence by RT
      PCR was 1.1% (45/4,052) while seroprevalence by ELISA was 0.8% (24/2,970). Virus
      prevalence was highest in domestic ducks (2.7%, 17/629) and turkeys (2.6%, 2/76),
      followed by free-living waterfowl (1.3%, 12/929) and swine (1.4%, 7/511). A lower
      proportion of chicken samples (0.4%, 7/1,865) tested positive. No influenza A
      virus was isolated. A seasonal prevalence of these viruses in waterfowl was 0.7%
      (4/561) for the dry and 2.2% (8/368) for the wet season. In poultry, prevalence
      was 0.2% (2/863) for the dry and 1.4% (24/1,713) for the wet season, while that
      of swine was 0.0% (0/159) and 2.0% (7/352) in the two seasons, respectively. Of
      the 45 RT-PCR positive samples, 13 (28.9%) of them were H5 but none was H7. The
      19 swine sera positive for influenza antibodies by ELISA were positive for H1
      antibodies by HAI assay, but the subtype(s) of ELISA positive poultry sera could
      not be determined. Antibodies in the poultry sera could have been those against
      subtypes not included in the HAI test panel. CONCLUSIONS: The study has
      demonstrated occurrence of influenza A viruses in animals in Uganda. The results
      suggest that increase in volumes of migratory waterfowl in the country could be
      associated with increased prevalence of these viruses in free-living waterfowl
      and poultry.

PMID- 24576328
TI  - Atomic force microscopy investigation of the kinetic growth mechanisms of
      sputtered nanostructured Au film on mica: towards a nanoscale morphology control.
AB  - The study of surface morphology of Au deposited on mica is crucial for the
      fabrication of flat Au films for applications in biological, electronic, and
      optical devices. The understanding of the growth mechanisms of Au on mica allows
      to tune the process parameters to obtain ultra-flat film as suitable platform for
      anchoring self-assembling monolayers, molecules, nanotubes, and nanoparticles.
      Furthermore, atomically flat Au substrates are ideal for imaging adsorbate layers
      using scanning probe microscopy techniques. The control of these mechanisms is a
      prerequisite for control of the film nano- and micro-structure to obtain
      materials with desired morphological properties. We report on an atomic force
      microscopy (AFM) study of the morphology evolution of Au film deposited on mica
      by room-temperature sputtering as a function of subsequent annealing processes.
      Starting from an Au continuous film on the mica substrate, the AFM technique
      allowed us to observe nucleation and growth of Au clusters when annealing process
      is performed in the 573-773 K temperature range and 900-3600 s time range. The
      evolution of the clusters size was quantified allowing us to evaluate the growth
      exponent <z> = 1.88 +/- 0.06. Furthermore, we observed that the late stage of
      cluster growth is accompanied by the formation of circular depletion zones around
      the largest clusters. From the quantification of the evolution of the size of
      these zones, the Au surface diffusion coefficient was evaluated in D(T) = [(7.42
      * 10-13) +/- (5.94 * 10-14) m2/s]exp(-(0.33+/-0.04) eVkT). These quantitative
      data and their correlation with existing theoretical models elucidate the kinetic
      growth mechanisms of the sputtered Au on mica. As a consequence we acquired a
      methodology to control the morphological characteristics of the Au film simply
      controlling the annealing temperature and time. 

PMID- 24576327
TI  - Risk of anaphylaxis in opioid dependent persons: effects of heroin versus
      substitution substance.
AB  - BACKGROUND: Across Europe, illicit drug-related mortality has not declined
      despite ever increasing prevention measures. The cause of these deaths has
      traditionally been associated with overdose. Previous findings have revealed the
      appearance of non-lethal opioid concentrations, leading us to investigate a
      further cause of death. The symptoms of heroin intoxication with asphyxia and/or
      cardiovascular involvement resemble anaphylaxis, and therefore it has been
      speculated that such deaths might be caused by an allergic reaction. The study's
      aims were to investigate levels of allergic mediators in long-term injecting drug
      users (IDU) compared to healthy controls and to determine if oral opioid
      substitution therapy (OST) resulted in similar allergic symptoms to those
      reported by IDU after intravenous (IV) heroin use. METHODS: We quantified the
      concentrations of histamine, diamine oxidase (DAO), tryptase and lipoprotein
      associated phospholipase A2 (LpPLA2) at baseline and 1 h after administration of
      Substitol(r)retard (482 +/- 220 mg) in 56 patients at a withdrawal centre
      (Austria) and compared them with healthy controls (n = 103). Questionnaires and
      face-to-face interviews were used to assess allergic symptoms and side effects in
      IDU. Descriptive statistical analyses of quantitative data were performed by
      using SPSS. RESULTS: Baseline histamine, tryptase and LpPLA2 were significantly
      elevated in IDU compared to the healthy control group, while DAO decreased. Blood
      levels showed no significant change after oral substitution uptake. Self-reported
      allergic symptoms and side effects after IV heroin use were reported in 55 cases
      (98.2%), minimal symptoms were documented after OST (12.5%, 7/56). CONCLUSIONS:
      This study revealed that baseline histamine concentrations were elevated in
      chronic IDU, although only relatively small changes in tryptase plasma levels
      occurred. After IV heroin application the reported allergic symptoms were mostly
      mild and did not lead to clinically relevant side effects. The substitution
      substance was clearly better tolerated than IV administered heroin. Elevated
      levels of allergic mediators such as histamine in IDUs may place them at greater
      risk of severe or fatal anaphylaxis when exposed to heroin; however, this
      requires further investigation.

PMID- 24576329
TI  - Effect of exenatide on the cardiac expression of adiponectin receptor 1 and NADPH
      oxidase subunits and heart function in streptozotocin-induced diabetic rats.
AB  - BACKGROUND: This study investigated the effect of exenatide on the cardiac
      expression of adiponectin receptor 1 and nicotinamide adenine dinucleotide
      phosphate (NADPH) oxidase subunits and heart function in streptozotocin-induced
      diabetic rats. METHODS: Male Sprague-Dawley rats were randomly divided into four
      groups, i.e. control group, diabetic group, diabetic treated with low doses of
      exenatide (2 MUg . kg-1.d-1) and diabetic treated with high doses of exenatide
      (10 MUg . kg-1.d-1). Diabetes was induced by intraperitoneal injection of
      streptozotocin (65 mg/kg body weight). At the termination after exenatide
      treatment for eight weeks, following anesthesia of the rats, a catheter was
      inserted into the left ventricle through the right common carotid artery for
      measurement of left ventricular pressure, which included left ventricular
      systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP) and the
      maximal rate of rise and decline of ventricular pressure (+/-dp/dt[max]). Plasma
      and myocardial adiponectin levels, and the expressions of myocardial adiponectin
      receptor 1, p22phox, NADPH oxidase 4 (NOX4), glucose transporter type 4 (Glut4),
      AMPK-alpha, phosphorylated-AMPK-alpha, connective tissue growth factor (CTGF) and
      copper zinc superoxide dismutase (Cu-Zn-SOD) were assayed. RESULTS: Heart
      function, plasma adiponectin levels, the protein expression of myocardial
      phosphorylated-AMPK-alpha, the mRNA expression of myocardial Glut4, and the
      positive expression of myocardial Cu-Zn-SOD were significantly decreased in
      diabetic. The protein expression of myocardial adiponectin receptor 1, the mRNA
      expression of myocardial p22phox and NOX4, and the positive expression of
      myocardial CTGF were significantly increased in diabetic. Low and high doses of
      exenatide treatment significantly attenuated these changes in diabetic rats.
      CONCLUSIONS: These results suggest that exenatide may contribute to the
      improvement of the heart function in diabetic rats by down-regulating the
      expression of myocardial adiponectin receptor 1, p22phox and NOX4, and up
      regulating plasma adiponectin level and the expression of myocardial AMPK-alpha,
      Glut4 and Cu-Zn-SOD.

PMID- 24576330
TI  - Extinction, coexistence, and localized patterns of a bacterial population with
      contact-dependent inhibition.
AB  - BACKGROUND: Contact-dependent inhibition (CDI) has been recently revealed as an
      intriguing but ubiquitous mechanism for bacterial competition in which a species
      injects toxins into its competitors through direct physical contact for growth
      suppression. Although the molecular and genetic aspects of CDI systems are being
      increasingly explored, a quantitative and systematic picture of how CDI systems
      benefit population competition and hence alter corresponding competition outcomes
      is not well elucidated. RESULTS: By constructing a mathematical model for a
      population consisting of CDI+ and CDI- species, we have systematically
      investigated the dynamics and possible outcomes of population competition. In the
      well-mixed case, we found that the two species are mutually exclusive:
      Competition always results in extinction for one of the two species, with the
      winner determined by the tradeoff between the competitive benefit of the CDI+
      species and its growth disadvantage from increased metabolic burden. Initial
      conditions in certain circumstances can also alter the outcome of competition. In
      the spatial case, in addition to exclusive extinction, coexistence and localized
      patterns may emerge from population competition. For spatial coexistence,
      population diffusion is also important in influencing the outcome. Using a set of
      illustrative examples, we further showed that our results hold true when the
      competition of the population is extended from one to two dimensional space.
      CONCLUSIONS: We have revealed that the competition of a population with CDI can
      produce diverse patterns, including extinction, coexistence, and localized
      aggregation. The emergence, relative abundance, and characteristic features of
      these patterns are collectively determined by the competitive benefit of CDI and
      its growth disadvantage for a given rate of population diffusion. Thus, this
      study provides a systematic and statistical view of CDI-based bacterial
      population competition, expanding the spectrum of our knowledge about CDI systems
      and possibly facilitating new experimental tests for a deeper understanding of
      bacterial interactions.

PMID- 24576331
TI  - Gender differences in emotionality and sociability in children with autism
      spectrum disorders.
AB  - BACKGROUND: Four times as many males are diagnosed with high functioning autism
      compared to females. A growing body of research that focused on females with
      autism spectrum disorder (ASD) questions the assumption of gender invariance in
      ASD. Clinical observations suggest that females with ASD superficially
      demonstrate better social and emotional skills than males with ASD, which may
      camouflage other diagnostic features. This may explain the under-diagnosis of
      females with ASD. METHODS: We hypothesised that females with ASD would display
      better social skills than males with ASD on a test of friendship and social
      function. One hundred and one 10- to 16-year-olds (ASD females, n = 25; typically
      developing (TD) females, n = 25; ASD males, n = 25; TD males, n = 26) were
      interviewed (using the friendship questionnaire (FQ)) with high scores indicating
      the child has close, empathetic and supportive relationships. One parent of each
      child completed the FQ to assess whether there are differences in perception of
      friendships between parents and children. RESULTS: It was found that, independent
      of diagnosis, females demonstrated higher scores on the FQ than males. Further,
      regardless of gender, children with ASD demonstrated lower scores than TD
      children. Moreover, the effect of ASD was independent of gender. Interestingly,
      females with ASD and TD males displayed similar scores on the FQ. CONCLUSIONS:
      This finding is supported by clinical reports that females with ASD have more
      developed social skills than males with ASD. Further research is now required to
      examine the underlying causes for this phenomenon in order to develop gender
      appropriate diagnostic criteria and interventions for ASD.

PMID- 24576334
TI  - Cerebrospinal fluid lactate level as a diagnostic biomarker for bacterial
      meningitis in children.
AB  - BACKGROUND: Cerebrospinal fluid (CSF) lactate is a potential biomarker for
      bacterial meningitis in children. To this end, we performed a single-center
      retrospective cohort study of children from Sao Paulo, Brazil, with CSF
      pleocytosis to evaluate the ability of CSF lactate to distinguish between
      children with bacterial and aseptic meningitis. We determined the optimum cutoff
      point for CSF lactate using receiver-operator curve (ROC) analysis. FINDINGS: We
      identified 451 children of whom 40 (9%) had bacterial meningitis. Children with
      bacterial meningitis had a higher median CSF lactate level [9.6 mmol/l,
      interquartile range (IQR) 3.2-38.5 mmol/l bacterial meningitis vs. 2.0 mmol/l,
      IQR 1.2-2.8 mmol/l aseptic meningitis]. A CSF lactate cutoff point of 3.0 mmol/l
      had a sensitivity of 95% [95% confidence interval (CI) 83-99%), specificity of
      94% (95% CI 90-96%) and negative predictive value of 99.3% (95% CI 97.7-99.9%)
      for bacterial meningitis. CONCLUSIONS: In combination with a validated meningitis
      clinical prediction rule, the CSF lactate level can be used to distinguish
      between bacterial and aseptic meningitis in children with CSF pleocytosis.

PMID- 24576333
TI  - The effect of intranasal oxytocin versus placebo treatment on the autonomic
      responses to human sounds in autism: a single-blind, randomized, placebo
      controlled, crossover design study.
AB  - BACKGROUND: Many individuals with autism spectrum disorders (ASD) have difficulty
      with verbal communication, which might be due to a lack of spontaneous
      orientation toward social auditory stimuli. Previous studies have shown that a
      single dose of oxytocin improves speech comprehension in autism. The primary aim
      of this study was to investigate whether the orientation behaviors toward human
      sounds are different for neurotypical (NT) adults and adults with ASD and whether
      oxytocin has an effect on their orientation behaviors toward human sounds.
      METHODS: This was a randomized, placebo-controlled, within-subject, crossover
      design study of intranasal oxytocin versus placebo in 13 NT adults and 16 adults
      with ASD. Subjects were randomized to 24 IU intranasal oxytocin or placebo on
      different days, and they were blind to the treatment. The participants then
      listened passively to human and non-human affective sounds while their skin
      conductance responses (SCRs) and the changes in peripheral blood vessel
      constriction were monitored as an indicator of spontaneous orientation. The
      monitored data were analyzed by a mixed-design ANOVA. RESULTS: Oxytocin enhanced
      the difference between the SCRs to human and non-human sounds in both the NT and
      ASD groups (F(1,56) = 6.046, p = 0.017). Further correlation coefficient analysis
      showed significant correlations between this SCR difference and the scores in the
      autism spectrum quotient 'attention to detail' and 'social skill' subscales and
      interpersonal reactivity index and social functioning scale in the ASD group.
      Oxytocin was well tolerated, and no serious adverse effects were reported.
      CONCLUSIONS: The difference in SCRs implies that oxytocin nasal spray may enhance
      orientation behaviors toward human sounds in the presence of other environmental
      sounds in both ASD and NT adults. TRIAL REGISTRATION: UMIN-CTR Clinical Trial,
      Unique trial number: UMIN000005809.

PMID- 24576335
TI  - Glatiramer acetate does not protect from acute ischemic stroke in mice.
AB  - BACKGROUND: The role of the immune system in the pathophysiology of acute
      ischemic stroke is increasingly recognized. However, targeted treatment
      strategies to modulate immunological pathways in stroke are still lacking.
      Glatiramer acetate is a multifaceted immunomodulator approved for the treatment
      of relapsing-remitting multiple sclerosis. Experimental studies suggest that
      glatiramer acetate might also work in other neuroinflammatory or
      neurodegenerative diseases apart from multiple sclerosis. FINDINGS: We evaluated
      the efficacy of glatiramer acetate in a mouse model of brain ischemia/reperfusion
      injury. 60 min of transient middle cerebral artery occlusion was induced in male
      C57Bl/6 mice. Pretreatment with glatiramer acetate (3.5 mg/kg bodyweight) 30 min
      before the induction of stroke did not reduce lesion volumes or improve
      functional outcome on day 1. CONCLUSIONS: Glatiramer acetate failed to protect
      from acute ischemic stroke in our hands. Further studies are needed to assess the
      true therapeutic potential of glatiramer acetate and related immunomodulators in
      brain ischemia.

PMID- 24576336
TI  - Poorer glycaemic control is associated with increased skin thickness at injection
      sites in children with type 1 diabetes.
AB  - We aimed to assess the association between skin thickness and glycaemic control
      in children with type 1 diabetes. Forty-five children (51% males) aged 10.5 +/-
      2.1 years were studied. Thickness of skin layers were determined by
      ultrasonography, with participants having ultrasound scans of three anatomical
      regions (abdomen, thigh, and buttocks). Poorer glycaemic control (increasing
      HbA1c values) was associated with greater thickness of the dermis (p = 0.015),
      with an estimated thickening of 87 MUm with every 1% increase in HbA1c. Our data
      suggest that dermal changes associated with poorer glycaemic control in adults
      are also observed in childhood. 

PMID- 24576332
TI  - Computational prediction of the human-microbial oral interactome.
AB  - BACKGROUND: The oral cavity is a complex ecosystem where human chemical compounds
      coexist with a particular microbiota. However, shifts in the normal composition
      of this microbiota may result in the onset of oral ailments, such as
      periodontitis and dental caries. In addition, it is known that the microbial
      colonization of the oral cavity is mediated by protein-protein interactions
      (PPIs) between the host and microorganisms. Nevertheless, this kind of PPIs is
      still largely undisclosed. To elucidate these interactions, we have created a
      computational prediction method that allows us to obtain a first model of the
      Human-Microbial oral interactome. RESULTS: We collected high-quality experimental
      PPIs from five major human databases. The obtained PPIs were used to create our
      positive dataset and, indirectly, our negative dataset. The positive and negative
      datasets were merged and used for training and validation of a naive Bayes
      classifier. For the final prediction model, we used an ensemble methodology
      combining five distinct PPI prediction techniques, namely: literature mining,
      primary protein sequences, orthologous profiles, biological process similarity,
      and domain interactions. Performance evaluation of our method revealed an area
      under the ROC-curve (AUC) value greater than 0.926, supporting our primary
      hypothesis, as no single set of features reached an AUC greater than 0.877. After
      subjecting our dataset to the prediction model, the classified result was
      filtered for very high confidence PPIs (probability >= 1-10-7), leading to a set
      of 46,579 PPIs to be further explored. CONCLUSIONS: We believe this dataset holds
      not only important pathways involved in the onset of infectious oral diseases,
      but also potential drug-targets and biomarkers. The dataset used for training and
      validation, the predictions obtained and the network final network are available
      at http://bioinformatics.ua.pt/software/oralint.

PMID- 24576337
TI  - mRNA translation and protein synthesis: an analysis of different modelling
      methodologies and a new PBN based approach.
AB  - BACKGROUND: mRNA translation involves simultaneous movement of multiple ribosomes
      on the mRNA and is also subject to regulatory mechanisms at different stages.
      Translation can be described by various codon-based models, including ODE, TASEP,
      and Petri net models. Although such models have been extensively used, the
      overlap and differences between these models and the implications of the
      assumptions of each model has not been systematically elucidated. The selection
      of the most appropriate modelling framework, and the most appropriate way to
      develop coarse-grained/fine-grained models in different contexts is not clear.
      RESULTS: We systematically analyze and compare how different modelling
      methodologies can be used to describe translation. We define various
      statistically equivalent codon-based simulation algorithms and analyze the
      importance of the update rule in determining the steady state, an aspect often
      neglected. Then a novel probabilistic Boolean network (PBN) model is proposed for
      modelling translation, which enjoys an exact numerical solution. This solution
      matches those of numerical simulation from other methods and acts as a
      complementary tool to analytical approximations and simulations. The advantages
      and limitations of various codon-based models are compared, and illustrated by
      examples with real biological complexities such as slow codons, premature
      termination and feedback regulation. Our studies reveal that while different
      models gives broadly similiar trends in many cases, important differences also
      arise and can be clearly seen, in the dependence of the translation rate on
      different parameters. Furthermore, the update rule affects the steady state
      solution. CONCLUSIONS: The codon-based models are based on different levels of
      abstraction. Our analysis suggests that a multiple model approach to
      understanding translation allows one to ascertain which aspects of the
      conclusions are robust with respect to the choice of modelling methodology, and
      when (and why) important differences may arise. This approach also allows for an
      optimal use of analysis tools, which is especially important when additional
      complexities or regulatory mechanisms are included. This approach can provide a
      robust platform for dissecting translation, and results in an improved predictive
      framework for applications in systems and synthetic biology.

PMID- 24576338
TI  - Phase 1 results of safety and tolerability in a rush oral immunotherapy protocol
      to multiple foods using Omalizumab.
AB  - BACKGROUND: Up to 30% of patients with food allergies have clinical reactivity to
      more than one food allergen. Although there is currently no cure, oral
      immunotherapy (OIT) is under investigation. Pilot data have shown that omalizumab
      may hasten the ability to tolerate over 4 g of food allergen protein. OBJECTIVE:
      To evaluate the safety and dose tolerability of a Phase 1 Single Site OIT
      protocol using omalizumab to allow for a faster and safe desensitization to
      multiple foods simultaneously. METHODS: Participants with multiple food allergies
      received OIT for up to 5 allergens simultaneously with omalizumab (rush mOIT).
      Omalizumab was administered for 8 weeks prior to and 8 weeks following the
      initiation of a rush mOIT schedule. Home reactions were recorded with diaries.
      RESULTS: Twenty-five (25) participants were enrolled in the protocol (median age
      7 years). For each included food, participants had failed an initial double-blind
      placebo-controlled food challenge at a protein dose of 100 mg or less. After pre
      treatment with omalizumab, 19 participants tolerated all 6 steps of the initial
      escalation day (up to 1250 mg of combined food proteins), requiring minimal or no
      rescue therapy. The remaining 6 were started on their highest tolerated dose as
      their initial daily home doses. Participants reported 401 reactions per 7,530
      home doses (5.3%) with a median of 3.2 reactions per 100 doses. Ninety-four
      percent (94%) of reactions were mild. There was one severe reaction. Participants
      reached their maintenance dose of 4,000 mg protein per allergen at a median of 18
      weeks. CONCLUSION: These phase 1 data demonstrate that rush OIT to multiple foods
      with 16 weeks of treatment with omalizumab could allow for a fast desensitization
      in subjects with multiple food allergies. Phase 2 randomized controlled trials
      are needed to better define safety and efficacy parameters of multi OIT
      experimental treatments with and without omalizumab.

PMID- 24576339
TI  - Differential enrichment of regulatory motifs in the composite network of protein
      protein and gene regulatory interactions.
AB  - BACKGROUND: An important aspect of molecular interactions is the dynamics
      associated with growth conditions. Intuitively, not all possible interactions
      take place together all the time in a cell as only a subset of genes is expressed
      based on environmental conditions. RESULTS: Large scale gene expression data of
      Escherichia coli was analyzed to understand the dynamics exhibited at expression
      level. A large compendium of gene expression datasets, which covers about 466
      growth conditions, was used for the analysis. Using gene expression data, genes
      of E. coli were profiled into three classes: Widely expressed, Conditionally
      expressed and Rarely expressed. Further, dynamics associated with molecular
      interactions were analysed by studying changing importance of motifs in the
      composite networks across growth conditions. CONCLUSIONS: Our analysis of large
      scale gene expression data suggests conditional expression of genes which brings
      about befitting responses for a given growth environment. We observe a range of
      importance for network motifs across conditions which can be correlated with a
      specific function. Our study therefore suggests rewiring of molecular
      interactions driven by gene expression changes depending on the conditional
      needs.

PMID- 24576340
TI  - Hepatic steatosis secondary to capecitabine: a case report.
AB  - INTRODUCTION: There are no known case reports of hepatic steatosis caused by oral
      fluoropyrimidines such as capecitabine. With increasing use of capecitabine since
      its approval for the treatment of metastatic colon cancer in 2001, and more
      recently for adjuvant treatment of colon cancer and treatment of metastatic
      breast cancer, we can anticipate increased recognition of potential toxicities
      associated with this 5-fluorouracil derivative. CASE PRESENTATION: We report the
      case of a 74-year-old Armenian woman who received capecitabine as adjuvant
      treatment for colon cancer and subsequently developed abnormal liver biochemical
      tests and radiographic findings in keeping with hepatic steatosis. There was
      complete reversal of liver enzyme abnormalities with discontinuation of the drug
      and this patient represents a case of reversible liver injury due to
      capecitabine. CONCLUSION: In this original case report, capecitabine use was
      associated with hepatic steatosis. It is important for clinicians to recognize
      and monitor for this potential toxicity, which may be a cause of abnormal liver
      enzymes in this patient population.

PMID- 24576341
TI  - Severe postpartum sepsis with prolonged myocardial dysfunction: a case report.
AB  - INTRODUCTION: Severe sepsis during pregnancy or in the postpartum period is a
      rare clinical event. In non obstetric surviving patients, the cardiovascular
      changes seen in sepsis and septic shock are fully reversible five to ten days
      after their onset. We report a case of septic myocardial dysfunction lasting
      longer than ten days. To the best of our knowledge, this is the first report of
      prolonged septic myocardial dysfunction in a parturient. CASE PRESENTATION: A 24
      year old Hispanic woman with no previous medical history developed pyelonephritis
      and severe sepsis with prolonged myocardial dysfunction after a normal
      spontaneous vaginal delivery. CONCLUSIONS: Septic myocardial dysfunction may be
      prolonged in parturients requiring longer term follow up and pharmacologic
      treatment.

PMID- 24576342
TI  - Hydrothermal synthesis of MnO2/CNT nanocomposite with a CNT core/porous MnO2
      sheath hierarchy architecture for supercapacitors.
AB  - MnO2/carbon nanotube [CNT] nanocomposites with a CNT core/porous MnO2 sheath
      hierarchy architecture are synthesized by a simple hydrothermal treatment. X-ray
      diffraction and Raman spectroscopy analyses reveal that birnessite-type MnO2 is
      produced through the hydrothermal synthesis. Morphological characterization
      reveals that three-dimensional hierarchy architecture is built with a highly
      porous layer consisting of interconnected MnO2 nanoflakes uniformly coated on the
      CNT surface. The nanocomposite with a composition of 72 wt.% (K0.2MnO2.0.33
      H2O)/28 wt.% CNT has a large specific surface area of 237.8 m2/g. Electrochemical
      properties of the CNT, the pure MnO2, and the MnO2/CNT nanocomposite electrodes
      are investigated by cyclic voltammetry and electrochemical impedance spectroscopy
      measurements. The MnO2/CNT nanocomposite electrode exhibits much larger specific
      capacitance compared with both the CNT electrode and the pure MnO2 electrode and
      significantly improves rate capability compared to the pure MnO2 electrode. The
      superior supercapacitive performance of the MnO2/CNT nancomposite electrode is
      due to its high specific surface area and unique hierarchy architecture which
      facilitate fast electron and ion transport. 

PMID- 24576343
TI  - Humeral metastasis from a sacrococcygeal chordoma: a case report.
AB  - INTRODUCTION: Chordomas are rare tumors of the skeletal system that arise from an
      intra-osseous benign precursor of notochordal cells. They are mainly locally
      aggressive. However, metastases to other sites, including the humeri, resulting
      in pathological fractures have been reported. We report the case of a patient
      with a metastatic chordoma that produced a pathologic fracture of the humerus.
      CASE PRESENTATION: We report the case of a 60-year-old Iranian woman who
      presented with a fracture of her right humerus following a minor trauma. She had
      a history of a sacrococcygeal chordoma. Histological and immunohistochemical
      studies of the fracture site suggested the diagnosis of a chordoma. CONCLUSIONS:
      Chordoma is a rare tumor and rarely metastasizes, but it should be considered in
      the differential diagnosis of epithelioid bone tumors. The only current effective
      treatment for this type of tumor is carbon ion therapy. There is currently no
      effective medical therapy available for advanced chordoma, and this type of tumor
      is not very responsive to radiotherapy.

PMID- 24576344
TI  - Fabrication and electrical properties of MoS2 nanodisc-based back-gated field
      effect transistors.
AB  - Two-dimensional (2D) molybdenum disulfide (MoS2) is an attractive alternative
      semiconductor material for next-generation low-power nanoelectronic applications,
      due to its special structure and large bandgap. Here, we report the fabrication
      of large-area MoS2 nanodiscs and their incorporation into back-gated field effect
      transistors (FETs) whose electrical properties we characterize. The MoS2
      nanodiscs, fabricated via chemical vapor deposition (CVD), are homogeneous and
      continuous, and their thickness of around 5 nm is equal to a few layers of MoS2.
      In addition, we find that the MoS2 nanodisc-based back-gated field effect
      transistors with nickel electrodes achieve very high performance. The transistors
      exhibit an on/off current ratio of up to 1.9 * 105, and a maximum
      transconductance of up to 27 MUS (5.4 MUS/MUm). Moreover, their mobility is as
      high as 368 cm2/Vs. Furthermore, the transistors have good output characteristics
      and can be easily modulated by the back gate. The electrical properties of the
      MoS2 nanodisc transistors are better than or comparable to those values extracted
      from single and multilayer MoS2 FETs. 

PMID- 24576345
TI  - Renal abscess after the Fontan procedure: a case report.
AB  - INTRODUCTION: The Fontan procedure is an intervention that helps to correct
      single ventricle physiology. There are many known long-term complications of
      'Fontan physiology'. However, the occurrence of renal abscess in such patients
      has not yet been reported in the literature. The first generation of adults has
      now undergone the procedure and it is necessary to be aware of the long-term
      outcomes and complications associated with it. CASE PRESENTATION: We report the
      case of a 22-year-old South Indian man who had developed a staphylococcal renal
      abscess against a background of xanthogranulomatous pyelonephritis, nine years
      after Fontan surgery. He presented to our hospital with a high-grade fever of 25
      days duration but with no other symptoms. Physical examination identified
      costovertebral angle tenderness and pedal edema. An ultrasound scan revealed a
      mass in his left kidney. The results of a computed tomography scan were
      consistent with a renal abscess. Despite treatment with the appropriate
      parenteral antibiotics, there was no change in the size of the abscess and a left
      nephrectomy was performed as a curative procedure. CONCLUSIONS: The learning
      points here are manifold. It is important to be aware of the possibility of renal
      abscess in a post-procedural patient. The early diagnosis of a septic focus in
      the kidneymay help to prevent the rare outcome of nephrectomy.

PMID- 24576348
TI  - Paleoclimate and bubonic plague: a forewarning of future risk?
AB  - Pandemics of bubonic plague have occurred in Eurasia since the sixth century AD.
      Climatic variations in Central Asia affect the population size and activity of
      the plague bacterium's reservoir rodent species, influencing the probability of
      human infection. Using innovative time-series analysis of surrogate climate
      records spanning 1,500 years, a study in BMC Biology concludes that climatic
      fluctuations may have influenced these pandemics. This has potential implications
      for health risks from future climate change.

PMID- 24576347
TI  - Sanfilippo type A: new clinical manifestations and neuro-imaging findings in
      patients from the same family in Israel: a case report.
AB  - INTRODUCTION: Sanfilippo syndrome type A (mucopolysaccharidosis IIIA - MPS IIIA)
      is an autosomal recessive lysosomal storage disorder caused by a deficiency in
      sulfamidase. CASE PRESENTATION: Two daughters (13 and 11 years old) of a
      consanguineous Palestinian family from the Israeli Arab community were
      investigated clinically and genetically for the presence of progressive
      neurodegenerative disease, psychomotor retardation and behavioral abnormalities.
      Development was normal up to one year of age. Thereafter, progressive motor and
      speech delay started. Metabolic screening including glycosaminoglycans, karyotype
      testing and magnetic resonance imaging were normal. Later in the disease, they
      developed severe spasticity and intellectual disability with autistic features
      and incontinence. Magnetic resonance imaging revealed diffuse hypomyelination
      with thinning of the corpus callosum. Genetic examination through whole exome
      sequencing revealed a homozygous mutation c.416C >T (p.T139M) in the N
      sulfoglucosamine sulfohydrolase (SGSH) gene. Repeated biochemical testing at age
      11 and 13 revealed increased levels of glycosaminoglycans confirming the
      diagnosis of Sanfilippo syndrome type A. CONCLUSION: These cases were considered
      to be the first report of Sanfilippo syndrome in Israel. We recommend that if
      similar clinical features are present during childhood, it is preferred to go
      directly and primarily for a genetic diagnosis of Sanfilippo syndrome, then
      secondarily for other lysosomal storage disorders that may also be involved.

PMID- 24576349
TI  - Dual application of duckweed and azolla plants for wastewater treatment and
      renewable fuels and petrochemicals production.
AB  - BACKGROUND: Shortages in fresh water supplies today affects more than 1 billion
      people worldwide. Phytoremediation strategies, based on the abilities of aquatic
      plants to recycle nutrients offer an attractive solution for the bioremediation
      of water pollution and represents one of the most globally researched issues. The
      subsequent application of the biomass from the remediation for the production of
      fuels and petrochemicals offers an ecologically friendly and cost-effective
      solution for water pollution problems and production of value-added products.
      RESULTS: In this paper, the feasibility of the dual application of duckweed and
      azolla aquatic plants for wastewater treatment and production of renewable fuels
      and petrochemicals is explored. The differences in absorption rates of the key
      wastewater nutrients, ammonium and phosphorus by these aquatic macrophytes were
      used as the basis for optimization of the composition of wastewater effluents.
      Analysis of pyrolysis products showed that azolla and algae produce a similar
      range of bio-oils that contain a large spectrum of petrochemicals including
      straight-chain C10-C21 alkanes, which can be directly used as diesel fuel
      supplement, or a glycerin-free component of biodiesel. Pyrolysis of duckweed
      produces a different range of bio-oil components that can potentially be used for
      the production of "green" gasoline and diesel fuel using existing techniques,
      such as catalytic hydrodeoxygenation. CONCLUSIONS: Differences in absorption
      rates of the key wastewater nutrients, ammonium and phosphorus by different
      aquatic macrophytes can be used for optimization of composition of wastewater
      effluents. The generated data suggest that the composition of the petrochemicals
      can be modified in a targeted fashion, not only by using different species, but
      also by changing the source plants' metabolic profile, by exposing them to
      different abiotic or biotic stresses. This study presents an attractive,
      ecologically friendly and cost-effective solution for efficient bio-filtration of
      swine wastewater and petrochemicals production from generated biomass.

PMID- 24576350
TI  - Effects of physiotherapy on balance and unilateral vestibular hypofunction in
      vertiginous elderly.
AB  - BACKGROUND: We aimed to analyze the effect of a physical therapy protocol on
      unilateral vestibular hypofunction and overall balance in elderly with vertigo.
      METHODS: The study included nine subjects, four male subjects (68.5 +/- 11.09
      years old) and five females (72.4 +/- 7.09 years old). It was used the
      performance-oriented Mobility Assessment (POMA), to evaluate the balance and the
      Unterberger - Fukuda test for analysis of unilateral vestibular dysfunction
      through rotations and displacements of the body. We developed and applied a
      structured physical therapy protocol, consisting of group exercises. RESULTS: It
      was observed that after the protocol, all participants improved balance (33.9 +/-
      5.1 vs. 47.3 +/- 7.6, p < 0.0001) and displacement (111.1 +/- 38.0 vs. 53.3 +/-
      34.6, p = 0.0001). However, it was not found significant differences for
      rotation. CONCLUSION: The proposed protocol has contributed to an improvement in
      balance and vestibular dysfunction of the aged.

PMID- 24576351
TI  - Anti-lysophosphatidic acid antibodies improve traumatic brain injury outcomes.
AB  - BACKGROUND: Lysophosphatidic acid (LPA) is a bioactive phospholipid with a
      potentially causative role in neurotrauma. Blocking LPA signaling with the LPA
      directed monoclonal antibody B3/Lpathomab is neuroprotective in the mouse spinal
      cord following injury. FINDINGS: Here we investigated the use of this agent in
      treatment of secondary brain damage consequent to traumatic brain injury (TBI).
      LPA was elevated in cerebrospinal fluid (CSF) of patients with TBI compared to
      controls. LPA levels were also elevated in a mouse controlled cortical impact
      (CCI) model of TBI and B3 significantly reduced lesion volume by both
      histological and MRI assessments. Diminished tissue damage coincided with lower
      brain IL-6 levels and improvement in functional outcomes. CONCLUSIONS: This study
      presents a novel therapeutic approach for the treatment of TBI by blocking
      extracellular LPA signaling to minimize secondary brain damage and neurological
      dysfunction.

PMID- 24576353
TI  - Development of a scale for determining violence against infertile women: a scale
      development study.
AB  - BACKGROUND: To develop a scale to evaluate violence experienced among infertile
      women. METHOD: Three steps were followed in the development of the scale:
      Literature review and deep interviews to generate item pool, content validity
      testing, and administration of draft. Content validity was evaluated by experts.
      The draft scale was pilot-tested with a convenience sample of 30 women during
      their treatment. After the pilot-test, 166 infertile females filled the scale in
      the infertility clinic of a university hospital in Istanbul. RESULTS: For
      evaluation of construct validity, Kaiser-Mayer Olkin was 0.91. Bartlett test was
      statistically significant (p = 0.00). According to the results of analysis, 5
      domains were determined: "domestic violence", "social pressure", "punishment",
      "exposure to traditional practices" and "exclusion". The values of correlation of
      item were between 0.50 and 0.82. Item-total and subscale-total correlation varied
      between 0.57-0.91. The scale had good internal reliability, with Cronbach's Alpha
      coefficient of 0.96. The other coefficients of subscales varied between 0.80
      0.94. CONCLUSIONS: The scale called "Infertile Women's Exposure to Violence
      Determination Scale" indicates high reliability, good content and construct
      validity. Routine screening for domestic violence in infertility clinics is
      necessary to give affected women an opportunity to access appropriate health care
      and support services. On the other hand, common use of Infertile Women's Exposure
      to Violence Determination Scale in infertility clinics provides increased
      sensitivity and awareness by caregivers.

PMID- 24576352
TI  - Antinociceptive tolerance to NSAIDs microinjected into dorsal hippocampus.
AB  - BACKGROUND: Pain is characterized as a complex experience, dependent not only on
      the regulation of nociceptive sensory systems, but also on the activation of
      mechanisms that control emotional processes in limbic brain areas such as the
      amygdala and the hippocampus. Several lines of investigations have shown that in
      some brain areas, particularly the midbrain periaqueductal gray matter, rostral
      ventro-medial medulla, central nucleus of amygdala and nucleus raphe magnus,
      microinjections of non-steroidal anti-inflammatory drugs (NSAIDs) induce
      antinociception with distinct development of tolerance. The present study was
      designed to examine whether microinjection of NSAIDs, clodifen, ketorolac and
      xefocam into the dorsal hippocampus (DH) leads to the development of
      antinociceptive tolerance in male rats. METHODS: The experiments were carried out
      on experimental and control (with saline) white male rats. Animals were implanted
      with a guide cannula in the DH and tested for antinociception following
      microinjection of NSAIDs into the DH in the tail-flick (TF) and hot plate (HP)
      tests. Repeated measures of analysis of variance with post-hoc Tukey-Kramer
      multiple comparison tests were used for statistical evaluations. RESULTS: We
      found that microinjection of these NSAIDs into the DH induces antinociception as
      revealed by a latency increase in the TF and HP tests compared to controls
      treated with saline into the DH. Subsequent tests on days 2 and 3, however,
      showed that the antinociceptive effect of NSAIDs progressively decreased,
      suggesting tolerance developed to this effect of NSAIDs. Both pretreatment and
      post-treatment with the opioid antagonist naloxone into the DH significantly
      reduced the antinociceptive effect of NSAIDs in both pain models. CONCLUSIONS:
      Our results indicate that microinjection of NSAIDs into the DH induces
      antinociception which is mediated via the opioid system and exhibits tolerance.

PMID- 24576354
TI  - Inverse correlation between serum interleukin-6 and iron levels among Japanese
      adults: a cross-sectional study.
AB  - BACKGROUND: Interleukin-6 (IL-6) is a multifunctional cytokine that is produced
      by many different cell types, and plays an important role in the regulation of
      inflammation, immune responses, the acute-phase response, and hematopoiesis.
      Previous laboratory and clinical studies have shown that IL-6 causes a
      significant decrease in serum iron levels. Therefore, we conducted an
      epidemiological study to examine the association between serum IL-6 and iron
      levels. METHODS: In total, 280 Japanese individuals aged 20-78 years were
      enrolled when they visited a clinic located in an urban area for Helicobacter
      pylori (H. pylori) infection tests and subsequent eradication; 65.3% were
      infected with H. pylori. Subjects with gastric cancer, idiopathic
      thrombocytopenia, or IL-6 > 10 pg/mL were excluded from the study. Serum iron and
      IL-6 levels were measured using the 2-nitroso-5-(N-propyl-3-sulfopropylamino)
      phenol method and chemiluminescence enzyme immunoassay, respectively. RESULTS:
      Geometric mean iron and IL-6 levels were 111.5 MUg/dL and 1.77 pg/mL,
      respectively, for men, and 89.4 MUg/dL and 1.55 pg/mL, respectively, for women.
      The logarithm of serum iron levels was negatively correlated with the logarithm
      of IL-6 levels in men (r = -0.19, p = 0.047), but not in women (r = -0.035, p =
      0.65). Regression analysis, adjusted for sex, age, and H. pylori infection
      status, showed that the logarithm of serum iron levels was significantly
      associated with a decreased logarithm of IL-6 levels (beta = -0.053, p = 0.041).
      The odds ratio for low serum iron levels adjusted for sex, age, and H. pylori
      infection status was 7.88 (95% CI 1.29-48.06) in those with an IL-6 level > 4
      pg/mL. CONCLUSION: Lower serum iron levels are significantly associated with
      higher serum IL-6 levels among Japanese adults.

PMID- 24576355
TI  - Monitoring of gas station attendants exposure to benzene, toluene, xylene (BTX)
      using three-color chromosome painting.
AB  - BACKGROUND: Chronic exposure of BTX (benzene, toluene, xylene) may lead to
      progressive degeneration of bone marrow, aplastic anemia and/or leukemia. In
      Brazil there is no self-service fuel in gas stations and attendants fill the fuel
      themselves. Due to this they are chronically exposed to high concentration of
      BTX. Occupational exposure to benzene has been associated with increased
      chromosomal aberrations in peripheral blood lymphocytes. Fluorescence in situ
      hybridization (FISH) using whole chromosome painting (wcp) probes allows the
      rapid detection of chromosomal aberration. In the present study three-color wcp
      probes for chromosomes 1, 2 and 4 were used for monitoring 60 gas station
      attendants. RESULTS: Blood tests were done and interviews were conducted for each
      worker. For searching for possible associations between the clinical
      characteristics and the frequency of chromosomal aberrations the workers were
      divided into two groups (<= 10 chromosomal abnormalities per 1,000 metaphases and
      > 10 chromosomal abnormalities per 1,000 metaphases).The studied workers had a
      low median age (36 year), albeit long period of BTX exposure (median was 16
      years). Low prevalence of smoking and moderate consumption of alcoholic beverages
      were found in this population. The cytogenetic analysis showed 16.6% (10/60) of
      workers with a high frequency of chromosomal abnormalities (>10 chromosomal
      abnormalities per 1,000 metaphases). Translocations were the most frequently
      observed chromosome aberration. The statistical analysis revealed highly
      significant differences in skin color (p = 0.002) and a weak significant
      differences in gender (p = 0.052) distribution between the two groups.
      CONCLUSION: 16.6% of the studied population showed elevated frequencies of
      chromosomal abnormalities, which is highly likely to be correlated with their
      exposure to BTX during their work. Therefore, further studies are needed for
      better characterize the work associated damage of the genome in gas station
      workers. It is necessary to better understand the risks that these workers are
      exposed, so that we can be effective in preventing diseases and maintaining the
      health of these workers and possibly the offspring.

PMID- 24576356
TI  - The high-cost, type 2 diabetes mellitus patient: an analysis of managed care
      administrative data.
AB  - BACKGROUND: Type 2 diabetes mellitus (T2DM) affects 25.8 million individuals in
      the United States and exerts a substantial economic burden on patients, health
      care systems, and society. Few studies have categorized costs and resource use at
      the patient level. The goals of this study were to assess predictors of being a
      high-cost (HC) patient and compare HC T2DM patients with not high-cost (NHC) T2DM
      patients. METHODS: Using managed care administrative claims data, patients with
      two or more T2DM diagnoses between 2005 and 2010 were selected. Patients were
      followed for 1 year after their first observed T2DM diagnosis; patients not
      continuously enrolled during this period were excluded from the study. Study
      measures included annual health care expenditures by component (i.e., inpatient,
      outpatient, pharmacy, total). Patients accruing total costs in the top 10% of the
      overall cost distribution (i.e., patients with costs > $20,528) were classified
      as HC a priori; all other patients were considered NHC. To assess predictors of
      being HC, a logistic regression model was estimated, accounting for demographics;
      underlying comorbidity burden (using the Charlson Comorbidity Index [CCI] score);
      diagnoses of renal impairment, obesity, or hypertension; and receipt of insulin,
      oral antidiabetics only, or no antidiabetics. RESULTS: A total of 1,720,041
      patients met the inclusion criteria; 172,004 were HC. The mean (SD) CCI score for
      HC patients was 4.3 (3.0) versus 2.1 (1.7) for NHC patients. Mean (SD; upper 95%
      confidence interval-lower 95% confidence interval) annual per-patient costs were
      $56,468 ($65,604; $56,778-$56,157) among HC patients and $4,674 ($4,504; $4,695
      $4,652) among NHC patients. Inpatient care and pharmacy costs were higher for HC
      patients than for NHC patients. The strongest predictor of being an HC patient
      was having a CCI score of 2 or greater (odds ratio [OR] = 4.896), followed by a
      diagnosis of obesity (OR = 2.106), renal impairment (OR = 2.368), and insulin use
      (OR = 2.098). CONCLUSIONS: High-cost T2DM patients accrue approximately $52,000
      more in total annual health care costs than not high-cost T2DM patients. Patients
      were significantly more likely to be high-cost if they had comorbid conditions, a
      diagnosis of obesity, or used insulin.

PMID- 24576358
TI  - Electron microscopy and electron energy-loss spectroscopy study of Nd 1-x Sr x
      CoO 3-delta (0 <= x <= 1) system.
AB  - A solid solution of Nd 1-x Sr x CoO 3-delta (with x=0, 1/3, 2/3, and 1) has been
      prepared and characterized by a combination of X-ray diffraction, electron
      microscopy, and electron energy-loss spectroscopy (EELS). The structural
      characterization indicates that Nd-doped materials present an orthorhombic
      symmetry with a=?2xa p, b=?2xa p, and c=2xa p (a p refers to lattice parameter of
      simple cubic perovskite), while SrCoO2.5 has an orthorhombic symmetry with a=?2xa
      p, b=4xa p, and c=?2xa p. EELS analysis revealed that Co are in 3+ oxidation
      states but in different spin configurations.

PMID- 24576357
TI  - Genome sequencing of the high oil crop sesame provides insight into oil
      biosynthesis.
AB  - BACKGROUND: Sesame, Sesamum indicum L., is considered the queen of oilseeds for
      its high oil content and quality, and is grown widely in tropical and subtropical
      areas as an important source of oil and protein. However, the molecular biology
      of sesame is largely unexplored. RESULTS: Here, we report a high-quality genome
      sequence of sesame assembled de novo with a contig N50 of 52.2 kb and a scaffold
      N50 of 2.1 Mb, containing an estimated 27,148 genes. The results reveal novel,
      independent whole genome duplication and the absence of the Toll/interleukin-1
      receptor domain in resistance genes. Candidate genes and oil biosynthetic
      pathways contributing to high oil content were discovered by comparative genomic
      and transcriptomic analyses. These revealed the expansion of type 1 lipid
      transfer genes by tandem duplication, the contraction of lipid degradation genes,
      and the differential expression of essential genes in the triacylglycerol
      biosynthesis pathway, particularly in the early stage of seed development.
      Resequencing data in 29 sesame accessions from 12 countries suggested that the
      high genetic diversity of lipid-related genes might be associated with the wide
      variation in oil content. Additionally, the results shed light on the pivotal
      stage of seed development, oil accumulation and potential key genes for sesamin
      production, an important pharmacological constituent of sesame. CONCLUSIONS: As
      an important species from the order Lamiales and a high oil crop, the sesame
      genome will facilitate future research on the evolution of eudicots, as well as
      the study of lipid biosynthesis and potential genetic improvement of sesame.

PMID- 24576359
TI  - Dietary histidine requirement to reduce the risk and severity of cataracts is
      higher than the requirement for growth in Atlantic salmon smolts, independently
      of the dietary lipid source.
AB  - The present study was carried out to investigate whether the dietary histidine
      requirement to reduce cataract development is higher than that for growth in
      Atlantic salmon smolts (Salmo salar L.) after seawater transfer and whether
      dietary vegetable oils contribute to cataractogenesis. Duplicate groups of salmon
      smolts were fed ten experimental diets with either fish oil (FO) or a vegetable
      oil (VO) mix replacing 70 % FO and histidine at five target levels (10, 12, 14,
      16 and 18 g His/kg diet) for 13 weeks after seawater transfer. The VO diet-fed
      fish exhibited somewhat inferior growth and feed intakes compared with the FO
      diet-fed fish, irrespective of the dietary histidine concentration. Both cataract
      prevalence and severity were negatively correlated with the dietary histidine
      concentration, while lens N-acetyl-histidine (NAH) concentrations were positively
      correlated with it. The fatty acid profiles of muscle, heart and lens reflected
      that of the dietary oils to a descending degree and did not affect the observed
      cataract development. Muscle, heart and brain histidine concentrations reflected
      dietary histidine concentrations, while the corresponding tissue imidazole
      (anserine, carnosine and NAH) concentrations appeared to saturate differently
      with time. The expression level of liver histidase was not affected by the
      dietary histidine concentration, while the liver antioxidant response was
      affected in the VO diet-fed fish on a transcriptional level. The lowest severity
      of cataracts could be achieved by feeding 13.4 g His/kg feed, independently of
      the dietary lipid source. However, the present study also suggests that the
      dietary histidine requirement to minimise the risk of cataract development is
      14.4 g His/kg feed. 

PMID- 24576360
TI  - Validity of self-reported hypertension: findings from the Thai Cohort Study
      compared to physician telephone interview.
AB  - BACKGROUND: Surveys for chronic diseases, and large epidemiological studies of
      their determinants, often acquire data through self-report since it is feasible
      and efficient. We examined validity and associations of self-reported
      hypertension, as verified by physician telephone interview among participants in
      a large ongoing Thai Cohort Study (TCS). METHODS: The TCS investigates the health
      risk transition among distance learning Open University students living all over
      Thailand. It began in 2005 and at 4-year follow-up, 60 569 self-reported having
      or not having doctor diagnosed hypertension. Two hundred and forty participants
      were randomly selected from each of the "hypertension" and "normotension" self
      report groups. A Thai physician conducted a structured telephone interview with
      the sampled participants and classified them as having hypertension or
      normotension. The sensitivity, specificity, positive and negative predictive
      value (PPV and NPV) and overall accuracy of self-report were calculated. RESULTS:
      The sensitivity of self-reported hypertension was 82.4% and the specificity was
      70.7%. As true prevalence was simulated to vary from 1% to 50% the overall
      accuracy of self-report varied little from 71% to 75%. High sensitivity and
      negative predictive value related to female gender, younger age (?40 years),
      higher education attainment and not visiting a physician in the last 12 months.
      High specificity and positive predictive value related to female gender, older
      age, higher education attainment and visiting a doctor in the previous year.
      CONCLUSION: Self-report of hypertension had high sensitivity and good overall
      accuracy. This is acceptable for use in large studies of hypertension, and for
      estimating its population prevalence to help formulate health policy in Thailand.

PMID- 24576361
TI  - Examining waiting placement in hospital: utilization and the lived experience.
AB  - This mixed-methods study addressed the problem that although waiting placement is
      considered a major hospital utilization issue, minimal evidence exists to
      highlight the extent of it and the personal impact of waiting placement. An
      analysis of two years of complete hospital data for the Canadian province of
      Alberta was undertaken to examine waiting placement rates and describe waiting
      placement patients. Qualitative interviews and observations of elderly patients
      waiting in hospital for nursing home placement were also undertaken to gain an
      understanding of the lived experience of waiting for placement in hospital. Only
      1.8% of all inpatients were waiting placement with an ALC (Alternative Level of
      Care) designation, 80% of ALC waits were less than 41 days (mean=29.85,
      median=14), and 2.2% of total hospital bed days in these two years were used by
      ALC patients. Three qualitative themes emerged: (a) coming to a realization of
      this significant move, (b) waiting is boring and distressing, and (c) hospitals
      are not designed for waiting placement. The findings of this study should raise
      awareness that although relatively few people wait placement in hospital, there
      are some major possible negative effects of waiting for placement in hospital for
      those who wait; with remedies to address waiting placement care deficits needed.

PMID- 24576362
TI  - Water and sanitation hygiene knowledge attitude practice in urban slum settings.
AB  - BACKGROUND: Access to improved drinking water, sanitation and hygiene is one of
      the prime concerns around the globe. This study aimed at assessing water and
      sanitation hygiene-related attitude and practices, and quality of water in urban
      slums of south Delhi, India. METHODOLOGY: This pilot cross sectional study was
      performed during July 2013 across four urban slums of South Delhi. A convenient
      sample of 40 participants was enrolled. A modified version of previously
      validated questionnaire was used to gather information on socio-demographics,
      existing water and sanitation facilities and water treatment practices. Water
      quality testing was additionally performed using hydrogen sulphide (H2S) vials.
      RESULTS: Average age of participants was 36 years (SD=10). 83% of the
      participants perceived gastrointestinal tract infection as the most important
      health problem. 75% of the participants did not use any method for drinking water
      treatment. 45% of the participants consumed water from privately-owned tube well/
      bore well. Water shortage lasted two days or more (50%) at a stretch with severe
      scarcity occurring twice a year (40%). Females aged 15 years and above were
      largely responsible (93%) for fetching water from water source. 45% of the
      participants had toilets within their households. 53% of drinking water samples
      collected from storage containers showed positive bacteriological contamination.
      DISCUSSION: There is an urgent need to develop family centered educational
      programs that would enhance awareness about water treatment methods that are cost
      effective and easily accessible.

PMID- 24576363
TI  - Prevalence and trend of overweight and obesity among schoolchildren in Ahvaz,
      Southwest of Iran.
AB  - INTRODUCTION: Obesity is an important risk factor for some chronic diseases.
      Since the effect of obesity is long-standing, monitoring childhood obesity should
      be the first step in the health policy for interventions regarding early
      prevention of chronic diseases. In this study we aim to determine the prevalence
      of overweight and obesity among school children in the city of Ahvaz. METHODS: A
      cross-sectional survey was designed. A sample of 5811 children, 2904 (49.97%)
      boys and 2907 (50.03%) girls, was selected and their heights and weights were
      measured in 2012-2013 academic year. Measurements of height and weight were made
      by using calibrated equipment and according to standardized protocol with the
      children having light clothes and without wearing shoes. The adjusted odds ratio
      of obesity and overweight for age and sex were calculated from multiple logistic
      regression model. RESULTS: A total 685 (23.6%) of boys and 561 (19.3%) of girls
      were overweight. and 190(6.05%) of boys and 130 (4.5%) of girls were obese. The
      proportion of overweight and obese boys was significantly higher than that of
      girls (p<0.001). Logistic regression showed significant increase in the
      likelihood of being overweight with the increasing age OR=1.50, C.I.95%: (1.43,
      1.57). CONCLUSION: The prevalence of overweight and obesity increased markedly
      with age. This shows the importance of early prevention by doing interventions
      and training since the first year of primary school.

PMID- 24576364
TI  - Knowledge, attitudes and practices toward energy drinks among adolescents in
      Saudi Arabia.
AB  - The objective of this study is to explore the knowledge, attitudes and intake of
      energy drinks among adolescents in Saudi Arabia. A multi-stage stratified
      sampling procedure was carried out to select 1061 school children aged 12-19
      years, from Jeddah city, Saudi Arabia. A short self-reported questionnaire was
      administrated in order to collect the data. Of adolescents in the study, 45%
      drank energy drinks (71.3% males and 35.9% females; P<0.001). Advertisements were
      the main source of information on energy drinks (43%). The major reasons for
      consuming energy drinks were taste and flavour (58%), to 'try them' (51.9%) and
      'to get energy' (43%), albeit with significant differences between genders
      (P<0.001). About half of the adolescents did not know the ingredients of these
      drinks, and 49% did not know that they contain caffeine (P-values <0.006 and
      <0.001 between genders, respectively). The greater majority (67%) considered
      energy drinks to be soft drinks. The study indicates the need for Saudi
      adolescents to be warned on the over-consumption of energy drinks. The study
      brings to attention the need for educational programmes related to increasing
      awareness in the community of the health effects related to high consumption of
      energy drinks. 

PMID- 24576365
TI  - Predict attention deficit hyperactivity disorder? Evidence -based medicine.
AB  - BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is the most common
      behavioral disorders in children and recent studies reported a relationship
      between low levels of Vitamin D and incidence of ADHD. AIM: The aim of this study
      was to investigate the association between vitamin D deficiency and attention
      deficit hyperactivity disorder (ADHD). Also, to study the impact and role of
      vitamin D on the development of ADH in children. DESIGN: This is a case-control
      study which was conducted in children below 18 years of age from June 2011 to May
      2013 at the School Health and Primary Health care Clinics, Qatar. METHODS AND
      SUBJECTS: The study was based on 1,331 cases and 1,331 controls. The data
      collection instrument included socio-demographic & clinical data, physician
      diagnosis family history, BMI, and serum 25(OH) vitamin D, calcium, albumin,
      billirubin, magnesium, calcium, cholesterol, urea, triglyceride and phosphorus.
      Descriptive and univariate statistical analysis were performed. RESULTS: Of the
      total number of 3470 children surveyed, 1331 of ADHD and 1,331 of healthy
      children gave their consent to participate in this study. The mean age (+/- SD,
      in years) for ADHD versus control children was 10.63+/-3.4 vs. 10.77+/-3.4.
      Overweight (7.7% vs 9.4%) and obesity (4.6% vs 7.7%) were significantly lower in
      ADHD children compared to their counterparts (P=0.001). Vitamin D deficiency was
      considerably higher in ADHD children compared to healthy children.  The mean
      value of vitamin D in ADHD children was much lower than the normal value and
      there was a significant difference found in the mean values of vitamin D between
      ADHD (16.6+/-7.8 with median 16) and control children (23.5+/-9.9) (p<0.0001) and
      with median 23 (p = 0.006). Mean values of Calcium and phosphorous were
      significantly higher in control compared to ADHD children (p<0.001). 1331 of all
      ADHD children had 19.1% had severe vitamin D deficiency (< 10 ng/ml), 44.9% has
      moderate insufficient levels (between 10-20 ng/ml), 27.3% has mild insufficient
      levels (between 20-30 ng/ml) and only 8.1% of ADHD had sufficient serum vitamin D
      levels (>30 ng/ml). Multivariate logistic regression analysis revealed that
      household income, poor relationship between parents, mothers' occupation,
      consanguinity, BMI in percentiles, low duration of time under sun light, physical
      activity, low serum calcium level and low vitamin D level were considered as the
      main risk factors associated with the ADHD after adjusting for age, gender and
      other variables. CONCLUSION: The study showed that vitamin D deficiency was
      higher in ADHD children compared to healthy children. Supplementing infants with
      vitamin D might be a safe and effective strategy for reducing the risk of ADHD,
      but, further genomic and some other test and relevant studies need to be done.

PMID- 24576366
TI  - Hypertension among HIV-infected adults receiving highly active antiretroviral
      therapy (HAART) in Malaysia.
AB  - There are increasing researches about non-communicable disease such as elevated
      blood pressure among people living with HIV before and after initiation of highly
      active antiretroviral therapy (HAART). This cross-sectional study was designed to
      determine the prevalence of hypertension and associated risk factors among 340
      HIV-infected patients on antiretroviral therapy at a Malaysian public hospital
      providing HIV-related treatment. Data on socioeconomic background, anthropometry,
      medical history and dietary intake of the patients were collected. Hypertension
      is defined as blood pressure >=130/85 (mm Hg). Prevalence of hypertension was
      45.60% (n=155) of which 86.5% of the hypertensive group were male (n=134). The
      results showed that increase in age (OR 1.051, 95% confidence interval (CI) 1.024
      1.078), higher body mass index (OR 1.18, 95%CI 1.106-2.71), bigger waist
      circumference (OR 1.18, 95%CI 1.106-2.71), higher waist-hip ratio (OR 1.070,
      95%CI 1.034-1.106), higher fasting plasma glucose (OR 1.332, 95%CI 0.845-2.100)
      and percentage energy intake from protein >15 (OR 2.519, 95%CI 1.391-4.561) were
      significant risk factors for hypertension (p<0.001). After adjusting for other
      variables, increasing age (adjusted odds ratio (aOR) 1.069 95%CI 1.016-1.124,
      p=0.010), being male (aOR 3.026, 95%CI 1.175-7.794, p=0.022) and higher body mass
      index (aOR 1.26, 95%CI 1.032-1.551, p=0.024) were independently associated with
      hypertension. None of the antiretroviral therapy and immunologic factors was
      linked to hypertension. In conclusion hypertension among PLHIV was linked to the
      well-known risk factors such as age, gender and body mass index. With HAART,
      people can live longer by making monitoring and control of some reversible
      factors, especially excessive weight gain for maintaining quality of life. 

PMID- 24576367
TI  - Families' stressors and needs at time of cardio-pulmonary resuscitation: a
      Jordanian perspective.
AB  - BACKGROUND: During cardio-pulmonary resuscitation, family members, in some
      hospitals, are usually pushed to stay out of the resuscitation room. However,
      growing literature implies that family presence during resuscitation could be
      beneficial. Previous literature shows controversial belief whether or not a
      family member should be present during resuscitation of their relative. Some
      worldwide association such as the American Heart Association supports family
      witnessed resuscitation and urge hospitals to develop policies to ease this
      process. The opinions on family-witnessed resuscitation vary widely among various
      cultures, and some hospitals are not applying such policies yet. This study
      explores family members' needs during resuscitation in adult critical care
      settings. METHODS: This is a part of larger study. The study was conducted in six
      hospitals in two major Jordanian cities. A purposive sample of seven family
      members, who had experience of having a resuscitated relative, was recruited over
      a period of six months. Semi-structured interview was utilised as the main data
      collection method in the study. FINDINGS: The study findings revealed three main
      categories: families' need for reassurance; families' need for proximity; and
      families' need for support. The need for information about patient's condition
      was the most important need. Updating family members about patient's condition
      would reduce their tension and improve their acceptance for the end result of
      resuscitation. All interviewed family members wanted the option to stay beside
      their loved one at end stage of their life. Distinctively, most of family members
      want this option for some religious and cultural reasons such as praying and
      supplicating to support their loved one. CONCLUSIONS: This study emphasizes the
      importance of considering the cultural and religious dimensions in any family
      witnessed resuscitation programs. The study recommends that family members of
      resuscitated patients should be treated properly by professional communication
      and involving them in the treatment process. The implications concentrate on
      producing specific guidelines for allowing family-witnessed resuscitation in the
      Jordanian context. Finally, attaining these needs will in turn decrease stress of
      those witnessing resuscitation of their relative.

PMID- 24576368
TI  - Prioritizing the compensation mechanisms for nurses working in emergency
      department of hospital using fuzzy DEMATEL technique: a survey from Iran.
AB  - AIM AND BACKGROUND: Nursing professionals are the most important human resources
      that provide care in the Emergency Departments at hospitals. Therefore
      appropriate compensation for the services provided by them is considered as a
      priority. This study aims to identify and prioritize the factors affecting the
      compensation for services provided by the EDs nurses. METHODS: Twenty four
      nurses, hospital administrators, local and national health authorities
      participated in a cross sectional study conducted in 2012. The participants
      discussed on different compensation mechanisms for nurses' of EDs, in six groups
      according to Focus Group Discussion (FGD) technique, resulted in the adopted
      mechanisms. Opinions of the participants on the mechanisms were obtained via
      paired matrices using fuzzy logic. Decision Making Trial and Evaluation
      Laboratory (DEMATEL) technique was used for prioritizing the adopted mechanisms.
      FINDINGS: Among the compensation mechanisms for nurses of ED services, both
      Monthly fixed amounts (9.0382) and increasing the number of vacation days
      (9.0189) had highest importance. The lowest importance was given to the
      performance-based payment (8.9897). Monthly fixed amounts, increasing the number
      of vacation days, decreasing the working hours and performance-based payment were
      recognized as effective factors. Other mechanisms are prioritized as use of the
      facilities, increase in emergency tariff, job promotions, non-cash payments,
      continuing education, and persuasive years. CONCLUSION: According to the results,
      the nurses working in the EDS of the hospitals were more likely to receive non
      cash benefits than cash benefits as compensation.

PMID- 24576369
TI  - Elderly demand for family-based care and support: evidence from a social
      intervention strategy.
AB  - This paper examines the influence of the national health insurance scheme on
      elderly demand for family-based care and support. It contributes to the growing
      concern on the rapid increase in the elderly population globally using micro
      level social theory to examine the influence the health insurance has on elderly
      demand for family support. A qualitative case study approach is applied to
      construct a comprehensive and thick description of how the national health
      insurance scheme influences the elderly in their demand for family
      support.Through focused interviews and direct observation of six selected cases,
      in-depth information on primary carers, living arrangement and the interaction
      between the health insurance as structure and elders as agents are analyzed. The
      study highlights that the interaction between the elderly and the national health
      insurance scheme has produced a new stratum of relationship between the elderly
      and their primary carers. Consequently, this has created equilibrium between the
      elderly demand for support and support made available by their primary carers. As
      the demand of the elderly for support is declining, supply of support by family
      members for the elderly is also on the decline. 

PMID- 24576370
TI  - Premenstrual syndrome symptomatology among married women of fertile age based on
      methods of contraception (hormonal versus non-hormonal methods of contraception).
AB  - INTRODUCTION: Premenstrual syndrome (PMS) refers to the cyclic occurrence of a
      set of disturbing physical, emotional or behavioral alterations that are of
      sufficient severity to interfere with interpersonal relations and routine life.
      Normal variations in gonadal estrogen and progesterone lead to biochemical
      reactions in the brain, resulting in PMS symptoms. This study aims to investigate
      the prevalence of PMS and PMDD signs among married women of fertile age (MWFA)
      based on the methods of birth control. METHOD AND MATERIALS: In a descriptive
      study, a number of 400 married women referring to 20 family healthcare clinics
      that use contraceptive methods were recruited and PMS questionnaire were
      administered to them. RESULTS: From 400 subjects, 205 took oral contraceptive
      pills (hormonal methods of contraception) and 195 used other birth control
      methods (non-hormonal method). A number of 345 subjects (86.25%) at least
      experienced one PMS symptom and 55 subjects (13.75%) did not report any symptoms.
      Of those who use hormonal contraceptives (HCs), 182 (88.8%) reported PMS symptoms
      and 23(11.2) lacked any symptoms. CONCLUSION: About 86% of the subjects showed
      moderate to severe of PMS symptoms. Although using hormonal contraceptive method
      can theoretically reduce PMS symptoms, such effect was not observed in this
      study. The results of this research should be generalized with caution. Future
      studies are suggested.

PMID- 24576371
TI  - How effective are spiritual care and body manipulation therapies in pediatric
      oncology? A systematic review of the literature.
AB  - BACKGROUND: The effects of cancer and associated treatments have a considerable
      impact on the well-being and quality of life of pediatric oncology patients. To
      support children and their families, complementary and alternative medicines are
      seen by nurses and doctors as practical to integrate to the services offered by
      hospitals. OBJECTIVE: The purpose of this paper is to examine if the practice of
      complementary and alternative medicine, specifically spiritual care and
      treatments based on body manipulation, is likely to improve the health and well
      being of children suffering from cancer. METHOD: This objective is achieved
      through a systematic review of the literature. The level of evidence associated
      with each practice of complementary and alternative medicine was assessed
      according to the methodological design used by the studies reviewed. RESULTS AND
      CONCLUSION: Studies reviewed are of a methodological quality that could be
      described as fair due to the small sample size of patients and the existence of a
      number of biases in the conduct and analysis of these studies. However, results
      obtained are consistent from one study to another, allowing us to make certain
      recommendations. It is thus advisable to consider the introduction of
      hypnotherapy in pediatric oncology services. Based on the data collected, it is
      the complementary and alternative medicine with the most evidence in favor of
      effectiveness of the well-being of pediatric oncology patients, especially during
      painful procedures. It is also recommended to use art therapy and music therapy.
      Conversely, too little evidence is present to be able to recommend the use of
      acupuncture, chiropractic or osteopathy.

PMID- 24576372
TI  - Disclosing the truth: a dilemma between instilling hope and respecting patient
      autonomy in everyday clinical practice.
AB  - BACKGROUND: While medical ethics place a high value on providing truthful
      information to patients, disclosure practices are far from being the norm in many
      countries. Transmitting bad news still remains a big problem that health care
      professionals face in their every day clinical practice. AIMS: Through the review
      of relevant literature, an attempt to examine the trends in this issue worldwide
      will be made. METHOD: Various electronic databases were searched by the authors
      and through systematic selection 51 scientific articles were identified that this
      literature review is based on. RESULTS: There are many parameters that lead to
      the concealment of truth. Factors related to doctors, patients and their close
      environment, still maintain a strong resistance against disclosure of diagnosis
      and prognosis in terminally ill patients, while cultural influences lead to
      different approaches in various countries. Withholding the truth is mainly based
      in the fear of causing despair to patients. However, fostering a spurious hope,
      hides the danger of its' total loss, while it can disturb patient-doctor
      relationship.

PMID- 24576373
TI  - Risk factors on hypertensive disorders among Jordanian pregnant women.
AB  - Eight percent of pregnancies involve hypertensive disorders, which can have
      serious complications for mothers and children. There has only been minimal
      research into hypertension in pregnancy in developing countries, including
      Jordan. Therefore, this study aimed to identify how frequent certain risk factors
      that apply to hyper-tensive disorders during pregnancy were among women in the
      Jordanian capital of Amman. A prospective case-control study was conducted on 184
      Jordanian pregnant patients with hypertensive disorders and 172 age-matched
      control subjects recruited from the maternity ward of a tertiary public hospital
      in Amman city; they were followed-up until 85 days after the birth (late
      puerperium). A standardized questionnaire pilot-tested was completed by
      participants that included demographic data and known risk factors for
      hypertension in pregnancy. Statistical analysis SPSS was conducted to compare the
      frequency of risk factors using Fisher's exact test, chi-square, Student's t
      tests, as well as multivariate logistic regression was conducted to identify
      independent risk factors. The results showed that chronic hypertension, prenatal
      hypertension, family history of preeclampsia, diabetes, high BMI, nulliparity,
      previous preeclampsia history and low education level were identified as risk
      factors for hypertensive disorders in pregnancy in this population; Moreover,
      diabetes, chronic hypertension and family history of preeclampsia were found to
      be independent risk factors. The results of the study contribute to the currently
      limited knowledge about the modifiable risk factors for hypertensive disorders
      during pregnancy among the Jordanian population, and could therefore be extremely
      useful for clinicians providing prenatal care.

PMID- 24576374
TI  - Relationship between career motivation and perceived spiritual leadership in
      health professional educators: a correlational study in Iran.
AB  - BACKGROUND AND AIMS: Career motivation in university educators through efficient
      ways and appropriate with the educational system, is considered one of the
      important factors affecting education of students and their competence. This
      study aimed to determine the relationship between career motivation and spiritual
      leadership among a university of medical sciences in the west, Iran. METHODS:
      This descriptive, cross-sectional correlation study was conducted among the
      university educators of medical sciences in the west, Iran in 2012. All of the
      educators (N=230) were selected and recruited according to census method. The
      data were collected by two established self-completed questionnaires on spiritual
      leadership (SL) and career motivation. Data were analyzed statistically by
      parametric tests: Pearson correlation, independent student t-test and one-way
      analysis of variance (ANOVA). RESULTS: The Pearson correlation test identified a
      significant relationship between educators' career motivation and vision,
      altruistic love, hope/faith, meaning/calling and membership dimensions of
      spiritual leadership (p<0.05). The independent t-test detected a significant
      relationship between the 'hope/faith' (p=0.04) and organizational commitment
      (p=0.004) dimensions and the gender of educators. ANOVA revealed significant
      differences in educators' years of work experience and their overall career
      motivation (p=0.003) and the dimension of 'membership' (p<0.04). A significant
      relationship was found in 'altruistic love' and 'Hope/faith', and the educators'
      academic rank place in the university (p=0.03). Also a significant relationship
      was found in 'vision' (p=0.03) and 'altruistic love' (p=0.002) and 'membership'
      (p=0.04) dimensions, and the type of faculty. CONCLUSION: The results indicate
      that the dimensions of existence of spiritual leadership may have a positive
      relationship with educators' career motivation.

PMID- 24576375
TI  - The pattern of fruit and vegetable consumption among Saudi university students.
AB  - The positive benefits of consumption fruit and vegetable are well documented in
      studies of health and body weight maintain. A cross sectional study was conducted
      utilized street based survey among 960 female students at King Faisal University
      in AL-Hasa, Saudi Arabia, to investigate the daily consumption of fruits and
      vegetables and the psychosocial factors related to the consumption. Seventy-eight
      percent of students consuming <5 servings/day of fruit and vegetable with only
      22% of them consuming >=5 servings/day, majority of them are in the normal BMI
      category. For psychosocial factors the higher consumption group more
      knowledgeable about the daily consumption of fruit and vegetable, and had more
      confidence in eating fruit and vegetables under difficult circumstances with
      significant differences between the groups (P=0.000, P=0.045; respectively). Self
      efficacy was significantly predictor for recommended daily fruit and vegetable
      consumption (?=0.303, SE=0.023, P=0.000), but perceived barriers and knowledge
      not predictor for recommended daily consumption. The results of this study can be
      useful to design an intervention to promote fruit and vegetable intake among this
      target group. 

PMID- 24576376
TI  - The effect of group play therapy on social-emotional skills in pre-school
      children.
AB  - BACKGROUND: Childhood is important and critical period in human life. The
      foundation of ego is shaped in childhood. Play therapy is one of the successful
      strategies to help children with inner conflicts problems. This method of
      psychotherapy is base on the normal learning processes of children, provides
      solutions to relieve feelings of stress, and expands self-expression. Group play
      therapy can enhance the self-awareness, self- regulation, social communication,
      empathy and adoptability in children. METHODS: Present study investigated the
      effects of play therapy on relational and emotional skills of pre-school
      children. For this purpose, the total numbers of 372 pre-school children were
      randomly selected, and divided into two equal groups (case and control). In next
      step, the BUSSE-SR methodology was used for evaluation and comparison of self
      awareness, self-regulation, social interaction, empathy, adoptability, and
      control groups. Pre-test were performed for both groups and case group was
      involved in-group play therapy. According to the results of post-test,
      correlation of variables between case-control groups was examined by multivariate
      analysis of covariance. RESULTS: Frequency of boys and girls in our sample were
      51.3 and 48.7 percent, respectively. The mean age of children was 5.1+/-0.6 year.
      According to the results of present study, play therapy significantly enhanced
      the social-emotional skills (P< 0.001). Our findings are consistent with the
      results of previous studies in other nations with different environmental and
      cultural properties. In conclusion, it seems that play therapy can be used in pre
      school centers to help children learn problem-solving skills and communicate with
      others.

PMID- 24576377
TI  - The relationship between addiction and socio-demographic characteristics of
      Iranian newcomer prisoners.
AB  - Prison has proven to be a suitable environment for the identification of various
      socio-demographic characteristics of those individuals whose drug use, or related
      crimes lead to incarceration. Furthermore, the prison environment could also
      support increased understanding of both the pattern and the relationship between
      drug use and the incidence of crime and deviances. Using the survey method, this
      study examines the socio-demographic features of 2200 prisoners in seven
      provinces of Iran. More specifically; drug abuse patterns and the relationship
      among addiction, crime prevalence, and some personal as well as socio-demographic
      characteristics were studied. According to the findings, characteristics such as
      age, education level, economic status, urban and/or rural status, all have an
      effects on the rate of drug use and, on crime commitment and its re-occurrence.
      Accordingly, younger age, lower socioeconomic status and urban residence showed a
      relationship with tendency to commit crime and repeat it while employment had no
      significant effect. 

PMID- 24576378
TI  - Food advertisements in two popular U.S. parenting magazines: results of a five
      year analysis.
AB  - Obesity rates among American youth have prompted an examination of food
      advertisements geared towards children. Research indicates children's high
      exposure to these advertisements and their influence on food preferences. Less is
      known about the presence of these advertisements in parenting magazines. This
      study's objective was to examine prevalence of food advertisements in popular
      parenting magazines and identify products by USDA food category. We analyzed 116
      issues of two popular U.S. parenting magazines across five years. All food and
      beverage advertisements for USDA Food Category were coded. Breakfast cereals were
      coded for nutritional quality. The coding took place at varied libraries in New
      Jersey, in the United States. A total of 19,879 food and beverage products were
      analyzed. One-third of advertisements (32.5%) were for baked goods, snacks, and
      sweets -- products generally low in nutrient density. Two-thirds of the breakfast
      cereals were low in nutritional quality (64.6%). Beverages comprised 11% of the
      advertisements, fruit juices the highest proportion. Less than 3% of
      advertisements were for fruits and vegetables combined. No significant food
      product trends were evident across the five-year period. Food advertisements
      identified in parenting magazines were generally low in nutritional value.
      Additional research is necessary to determine the influence of food
      advertisements on parents' purchasing habits. 

PMID- 24576379
TI  - A cross-sectional study of facilitators and barriers of Iranian nurses'
      participation in continuing education programs.
AB  - BACKGROUND: Continuing education is one of the modern strategies to maintain and
      elevate knowledge and professional skills of nurses which in turn elevate the
      health status of society. Since several factors affect nurses' participation in
      continuing education, it's essential to know promoters and obstacles in this
      issue and plan accordingly. METHODS: In this cross-sectional study, 361 Iranian
      nurses who were recruited by convenience sampling method completed an anonymous,
      self-administered questionnaire from October 2012 to April 2013. Topics covered
      the participants' attitudes towards facilitators and barriers of their
      participation in continuing education. RESULTS: Mean and standard deviation of
      participants ' age were 37.14+/-7.58 years and 93.94% were female. The maximum
      score of facilitators and barriers to nurses' participation in continuing
      education were related to "Update my knowledge" and "Work commitments"
      respectively. The results showed among Iranian nurses, the mean score of personal
      and structural barriers was significantly higher than the mean score of
      interpersonal ones (F=2122.66, p<0.001). CONCLUSION: Results highlight policy
      makers and nursing managers' role on improving the accessibility to provided
      continuing education programs by enforcement of facilitators and reducing
      barriers focusing on the personal and structural barriers.

PMID- 24576381
TI  - The effects of aerobic exercise training on psychosocial aspects of men with type
      2 diabetes mellitus.
AB  - AIM: This study was conducted to examine the effects of aerobic exercise training
      on psychosocial aspects (mental health, the aspects of physical symptoms, anxiety
      and insomnia, social functioning, and depression) in patients with type 2
      diabetes mellitus. METHODS: 53 men who had type 2 diabetes mellitus for a mean
      duration of the disease for 3+/-5 years were selected purposely and classified
      randomly into experimental (27 patients) and a control group (26 patients).
      Patients in the experimental group did aerobic exercise training three times a
      week for eight weeks. The exercise included an aerobic activity for 45 to 60
      minutes during which the patients' heart rates were maintained at 60-70 percent
      of heart rate reserve on ergo meter bikes. RESULTS: The eight-week aerobic
      exercise training had significant effects on mental health (p = 0.002), subscales
      of physical symptoms (p = 0.006), and anxiety and insomnia (p = 0.001). It had no
      significant effects on subscales related to disorder of social functioning (p =
      0.117) and depression (p = 0.657). CONCLUSIONS: Aerobic exercise training can be
      considered as an appropriate program for improving the health of the patients
      with type 2 diabetes mellitus, and it also can improve their mental health.

PMID- 24576380
TI  - Betel nut usage is a major risk factor for coronary artery disease.
AB  - AIM: The objective of our study was to assess betel nut usage as one of the major
      risk factors associated with coronary artery disease. METHODS: This case control
      study consisted of 300 controls and 300 cases. A structured questionnaire was
      administered to the participants to assess consumption of betel nut and
      confounding variables. A respondent was considered a regular consumer of betel
      nut if he/she consumed one or more pieces of betel nut every day for a period of
      greater than 6 months. RESULTS: About 8 in 10 betel nut chewers developed
      coronary artery disease. After adjusting for diabetes and hypertension, the odds
      ratio analysis depicted 7.72 times greater likelihood for coronary artery disease
      in patients who chewed betel nut for more than 10 years. CONCLUSION: Our study
      concludes that betel nut chewing is a significant risk factor leading to the
      development of coronary artery disease.

PMID- 24576382
TI  - Psychological symptoms in family members of brain death patients in intensive
      care unit in Kerman, Iran.
AB  - AIM: Having patients in Intensive Care Unit (ICU) remains an extremely stressful
      live event for family members, especially for those having to confront with brain
      death patients. The aim of present study was to determine the prevalence of
      depression, anxiety and stress among relatives of brain dead patients in ICU in
      Kerman, Iran. METHODS: In a cross-sectional study, using DASS- 42 questionnaire,
      the symptoms of depression, anxiety and stress of family members of brain death
      patients were explored in Kerman, Iran. RESULTS: Of 244 eligible family members,
      224 participated in this study (response rate of 91%). Generally, 76.8%, 75% and
      70.1% of family members reported some levels of anxiety, depression and stress,
      respectively. More specifically, the rate of severe levels of anxiety, depression
      and stress among the participants were 48.7%, 33%, and 20.1% respectively.
      CONCLUSION: Prevalence of depression, anxiety and stress in family members of
      brain death patients in ICU remains high. Health care team members, especially
      nurses, should be aware and could consider this issue in the caring of family
      members of brain death patients.

PMID- 24576384
TI  - Effects of health education of diabetic patient's knowledge at Diabetic Health
      Centers, Khartoum State, Sudan: 2007-2010.
AB  - BACKGROUND: Educating and training diabetic patients is necessary for controlling
      and improving their health. METHODS: It was Quasi-experimental study design
      study. The study aimed to determine the effects of health education on the
      achievements of diabetic patients regarding control and improvement of their
      health status; at Diabetic Health Centers in Khartoum State, Sudan; 2007-2010.
      The target populations were diabetic patients, who attended the diabetic health
      centers to receive their treatment. Using simple random sampling 152 patients
      were selected (58 males and 94 females). Before and after comparison was done.
      Data was processed using SPSS and pair t-test was used to determine the effect of
      health education. P-value equal or less than 0.05 was considered statistically
      significant. FINDINGS: Test for before and after comparison was found to be
      statistically significant (p<0.05) for diabetic patients. They gained more
      knowledge after the implementation of the program; particularly in the areas of
      the nature and signs and symptoms of the disease, signs and symptoms of hypo &
      hyperglycemia, causes and warning signs of foot problems, foot care, and
      importance of exercises. CONCLUSIONS AND RECOMMENDATIONS: Health education of
      diabetic patients is crucial for control of diabetes. Capacity building of
      diabetic health centers, strengthening diabetic patients association, and more
      research to study the effect of health education on diabetic patients were
      needed.

PMID- 24576383
TI  - Dog ecology and population studies in Lagos State, Nigeria.
AB  - Dog population dynamics have a major impact upon the effectiveness of rabies
      control strategies. As such, understanding domestic dog ecology has been
      recognized as central to the design of effective rabies control programmes. This
      study was conducted to determine the dog ecology in Lagos State using compound
      dog count and street dog count in the three senatorial districts (Lagos West,
      East and Central) of Lagos State from February, 2011 to January, 2012. A total of
      546 questionnaires were distributed for the compound dog count and all were
      completed and returned. Various aspects of dog ecology were determined, including
      size, sex, breed of the dog population, management of dogs and rabies awareness
      among the respondents. Out of the 546 compounds surveyed, 518 (94.87%) owned at
      least one dog. A total of 1,427 dogs were counted from the street counts while a
      total of 1,447 dogs (2.8 dogs/compound) were counted from the compound count. The
      dogs comprised of 583 males and 864 females, out of which 64.10% are confined.
      The dog vaccination coverage in the dog population surveyed was 64.10% and
      administered majorly (91.30%) by veterinarians. Security (60%) and pets (26%)
      were the major reasons for keeping dogs. Majority (88.80%) of the respondents
      were aware of rabies and its mode of transmission, but still believed in the use
      of concoctions (40.40%), herbs (19.90%) and consumption of the organ of the
      offending dog (11.50%) for the treatment of rabies. The findings of this study
      showed a male: female ratio of dog to be 1:1.5 and a dog: human ratio of 1:5.6.
      There was also a responsible dog ownership as majority of the respondents do
      confine, vaccinate and provide food for their dogs. Vaccination coverage of the
      total dog population was however below the 70-80% target recommended by the World
      Health Organization to achieve herd immunity. 

PMID- 24576385
TI  - Chronic condition and risk behaviours in Portuguese adolescents.
AB  - Living with a chronic condition (CC) in adolescence has been historically
      considered protective for risk behaviours. However, research from the last decade
      suggest that when compared with healthy peers, adolescents living with a chronic
      condition can engage in risky behaviours in a similar if not higher rate than
      their counterparts living with out a CC. This study aims to characterize and
      evaluate the impact of 1) living with a chronic condition (CC), and 2) how the
      perception of living with a CC affects school participation, and its association
      with risk/protective behaviours (drunkenness, physical fight, sadness and self
      harm). For this purpose 4 groups were identified: adolescents with mostly healthy
      behaviours, adolescents with mostly risk behaviours, adolescents with mostly risk
      internalizing behaviours and adolescents with mostly risk-externalizing
      behaviours. A large sample was included in this study, composed by 3494
      Portuguese adolescents with an average age of 15 years, who participated in the
      Portuguese Survey of Health Behaviour in School-aged Children/WHO (HBSC). Main
      results show that adolescents living with a CC have more risk-internalizing
      behaviours when compared to adolescents without CC, who present more healthy
      behaviors. Furthermore, adolescents that report that having a CC affects school
      participation show more risky behaviours than those not affected by a CC who
      present more healthy behaviours. Boys with a CC show more healthy behaviours, and
      those who feel that the CC affects school participation present more risky
      behaviours. On the other hand, girls with a CC have more risk-internalizing
      behaviours and less healthy behaviours It is important to point out that
      adolescents living with a CC represent a vulnerable group, and may engage in
      experimental/risky behaviours as likely as their non CC peers. Thus, potential
      benefits can arise from reinforcing interventions within protective contexts
      (family/peers/school setting). Health/education professionals, more than
      considering risk behaviours as dangerous in themselves, should offer adolescents
      with a CC an opportunity to reflect on their own decisions. Educational programs
      would benefit from looking at risk behaviors more from an experimentation
      perspective, focusing on constructive ways to help adolescents with CC to proceed
      into adulthood in a more appropriate developmental way.

PMID- 24576386
TI  - Prerequisites of preparedness against earthquake in hospital system: a survey
      from Iran.
AB  - BACKGROUND AND OBJECTIVE: Considering the history of frequent, and severe,
      earthquakes in Iran and the importance of health care service delivery by
      hospitals in these cases, having a plan to deal with disasters should be
      considered a priority. The aim of this study was the observance of preparedness
      prerequisites against earthquake in hospitals affiliated with Shahid Beheshti
      University of Medical Sciences (SBUMS) and its relationship with demographic and
      organizational characteristics. METHODS: This was a cross- sectional study that
      was conducted in 15 hospitals affiliated with SBUMS, Iran in 2012. Data were
      collected using observation of documents and questionnaire consists of 138
      questions in 8 dimensions. The content validity and reliability were confirmed.
      Data analysis was performed with descriptive statistic, t-test and ANOVA.
      RESULTS: Results showed that 86.7% of hospitals were in good preparedness level,
      with the average 85.9 +/- 15.5. The maximum and minimum level of preparedness was
      related to mitigation of construction hazards (56.6 +/- 35.6) and support of
      vital services (97.2 +/- 6.0) dimensions, respectively. According to the results,
      there was a significant statistical difference between mean preparedness and
      safety of equipment and hazardous materials, hospital evacuation and field
      treatment, hospital environmental health proceedings, hospital curriculum
      programs and support of services dimensions with management experience (P<0.05).
      CONCLUSION: Although results corroborate that preparedness prerequisites against
      earthquake are in good level but attention to the weaknesses mitigation of
      construction hazards dimension and strengthening these prerequisites, which have
      obvious impacts on the structural vulnerability of hospitals and adjacent
      buildings in earthquakes, have been proposed.

PMID- 24576387
TI  - Menopause and crisis? Fake or real: comprehensive search to the depth of crisis
      experienced: a mixed-method study.
AB  - INTRODUCTION: Menopause is beyond the lack of menstruation and fertility decline
      in estrogen. Menopause is associated with at least three types of crisis:
      Biological, psychological and social. The aim of this study was to investigate
      psychiatric problems related to menopausal stress and experiences about
      psychological conditions related to menopause as a developmental crisis.
      MATERIALS AND METHODS: This mixed-method study (by triangulation approach) was
      done on 300 women in menopause age (44-54 years) by consensus sampling. Data
      gathering was from questionnaire conclude psychosomatic listed and hypochondria's
      criterion that has been specified by DSMIV. The severity of the disorder was also
      collected by self-reported question. In the qualitative part, as a phenomenology
      study, data were gathered with Purposive sampling by a deep semi-structured
      interview. Data analysis was from content analysis). RESULTS: Results showed that
      most of the disorders from psychosomatic listed experienced by women conclude:
      sexual problems 101(33.7%), hypertension 39(13%), and constipation 30(10%); 2.9%
      had experienced hypochondrias disorder. In the qualitative part, 5 themes were
      driven from the results of this study which described the structures of
      psychological experiences of the menopause as follows: change in emotion and
      mood, change in attitude, change in self-concept and change in interpersonal
      relationships. CONCLUSION: Menopause is a physiological process in women's life,
      but due to many symptoms and complications, it requires culturally appropriate
      education, appropriate coping with problems and mental health promotion in this
      sexual crisis.

PMID- 24576389
TI  - Variability of factors driving spatial and temporal dispersion in river plume and
      Chattonella antiqua bloom in the Yatsushiro Sea, Japan.
AB  - The dynamics of river plume in relation to harmful blooms of the raphidophycean
      flagellate, Chattonella antiqua in summer 2008-2010 in the Yatsushiro Sea, Japan
      were studied using a hydrodynamic model and monitoring data. In the southern
      area, the bloom formed in the waters stratified by a halocline caused by the
      southward expansion of riverine water from the Kuma River after the bloom
      initially forming in the northern area. The timing of the southward riverine
      water advection can be explained by the balance between the wind stress term and
      the pressure gradient term calculated from the horizontal density difference
      between the northern and southern areas. The wind stress and pressure gradient
      terms were evaluated using the sea surface temperature, salinity, wind speed and
      direction at two stations. Real time monitoring or continuous observations in
      these areas will enable nowcasts of bloom expansion when a bloom develops in the
      northern area. 

PMID- 24576388
TI  - Genome-wide discovery and characterization of maize long non-coding RNAs.
AB  - BACKGROUND: Long non-coding RNAs (lncRNAs) are transcripts that are 200 bp or
      longer, do not encode proteins, and potentially play important roles in
      eukaryotic gene regulation. However, the number, characteristics and expression
      inheritance pattern of lncRNAs in maize are still largely unknown. RESULTS: By
      exploiting available public EST databases, maize whole genome sequence annotation
      and RNA-seq datasets from 30 different experiments, we identified 20,163 putative
      lncRNAs. Of these lncRNAs, more than 90% are predicted to be the precursors of
      small RNAs, while 1,704 are considered to be high-confidence lncRNAs. High
      confidence lncRNAs have an average transcript length of 463 bp and genes encoding
      them contain fewer exons than annotated genes. By analyzing the expression
      pattern of these lncRNAs in 13 distinct tissues and 105 maize recombinant inbred
      lines, we show that more than 50% of the high confidence lncRNAs are expressed in
      a tissue-specific manner, a result that is supported by epigenetic marks.
      Intriguingly, the inheritance of lncRNA expression patterns in 105 recombinant
      inbred lines reveals apparent transgressive segregation, and maize lncRNAs are
      less affected by cis- than by trans-genetic factors. CONCLUSIONS: We integrate
      all available transcriptomic datasets to identify a comprehensive set of maize
      lncRNAs, provide a unique annotation resource of the maize genome and a genome
      wide characterization of maize lncRNAs, and explore the genetic control of their
      expression using expression quantitative trait locus mapping.

PMID- 24576390
TI  - The principles of effective post-spill environmental monitoring in marine
      environments and their application to preparedness assessment.
AB  - Understanding the fate and effects of marine spills is essential if the
      scientific and response communities are to develop best practices. The effective
      deployment of environmental monitoring activity can be complex and requires
      planning and coordination but the levels of preparedness to deliver the necessary
      expertise, coordination and funding are often low. This paper identifies and
      describes the importance of 8 principles of effective post-spill monitoring
      programmes. These principles are then used in the assessment of monitoring
      preparedness through the generation of a monitoring preparedness assessment score
      (MPAS). This approach can be used by local, regional or national authorities to
      establish the level of preparedness for environmental monitoring and prioritise
      areas for improvement. It also has value to responders, policy makers,
      environmental scientists and planners as a tool to assess preparedness and
      capability for specific scenarios. The approach is demonstrated through the
      assessment of previous incidents and potential future scenarios. 

PMID- 24576391
TI  - Assessment of susceptibility to pollution in littoral waters using the concept of
      recovery time.
AB  - Susceptibility to pollution can be related to the flushing capacity of aquatic
      systems. Transport time scales constitute a useful tool for representing the
      water exchange and transport processes. A new transport time scale, recovery
      time, and a methodology to estimate it by means of numerical models is hereby
      developed. Recovery time, calculated in Gijon, Santander and Tarragona harbours,
      is significantly related to physical, chemical and biological water quality
      indicators. Susceptibility, assessed through recovery time values, provides
      spatial patterns of expected flushing capacity, being sensitive to physical and
      hydrodynamic characteristics. The developed method is appropriate to estimate
      recovery time and assess susceptibility against pollution in littoral waters
      having great potential to be applied to different disciplines. Recovery time
      could be used in littoral waters as a surrogate of water quality indicators, to
      establish efficient monitoring programs, to define and characterize modified
      water bodies or to improve the design of marine infrastructures. 

PMID- 24576392
TI  - Naphthalene degradation in seawater by UV irradiation: the effects of fluence
      rate, salinity, temperature and initial concentration.
AB  - A large amount of oil pollution at sea is produced by the operational discharge
      of oily wastewater. The removal of polycyclic aromatic hydrocarbons (PAHs) from
      such sources using UV irradiation has become attractive, yet the photolysis
      mechanism in seawater has remained unclear. This study examines the
      photodegradation kinetics of naphthalene in natural seawater through a full
      factorial design of experiments (DOE). The effects of fluence rate, salinity,
      temperature and initial concentration are investigated. Results show that fluence
      rate, temperature and the interaction between temperature and initial
      concentration are the most influential factors. An increase in fluence rate can
      linearly promote the photodegradation process. Salinity increasingly impedes the
      removal of naphthalene because of the existence of free-radical scavengers and
      photon competitors. The results will help understand the photolysis mechanism of
      PAHs and develop more effective methods for treating oily seawater generated from
      offshore industries. 

PMID- 24576393
TI  - Sequential gene expression profiling in the mouse spleen during 14 d feeding with
      Lactobacillus brevis KB290.
AB  - Some lactic acid bacteria play an important role in the immune system with
      potential benefits to the host. However, detailed mechanisms of immune modulation
      exerted by probiotics remain to be clarified. Since immune response changes in a
      time-related manner in some cases, we monitored changes in mRNA levels in the
      spleen of mice during 14 d feeding with Lactobacillus brevis KB290 (KB290).
      Female BALB/c mice, aged 9 weeks, commenced a diet containing KB290 (3 * 109
      colony-forming units/g) or starch for a period of 1, 4, 7 or 14 d. Cytotoxic
      activity of the resulting splenocytes against YAC-1 cells was measured using flow
      cytometry. The activity was found to be significantly higher in the treated group
      on days 1 and 7. The highest activity appeared on day 4, but was not
      statistically significantly different. Gene expression profiles were analysed
      using DNA microarray. Gene Ontology (GO) terms related to the immune process were
      significantly enriched in the up-regulated gene set on days 1, 4 and 7, and GO
      terms related to the cellular process were enriched in the down-regulated gene
      set on days 4 and 7. Although the up-regulated genes involved in antigen
      processing and presentation for stimulation of CD8+ cytotoxic T cells were not
      observed on day 14, some genes involved in T-cell and natural killer cell
      activation remained up-regulated until day 14. For the majority of the genes
      tested, RT-PCR analysis was used to verify the results obtained from the DNA
      microarray analysis. The sequential gene expression profiling reflected changes
      in cytotoxic activity during KB290 feeding.

PMID- 24576394
TI  - Geographic access to diabetes prevention program sites: New York State Department
      of Health.

PMID- 24576395
TI  - Diabetes prevention in Hispanics: report from a randomized controlled trial.
AB  - INTRODUCTION: Hispanics are at increased risk of developing type 2 diabetes.
      Lifestyle interventions are effective in preventing diabetes and restoring
      glucose regulation. METHODS: We recruited Hispanic men and women (N = 320) who
      were residents of the Lower Yakima Valley, Washington, aged 18 years or older
      with hemoglobin A1c (HbA1c) levels higher than 6% to a parallel 2-arm randomized
      controlled trial conducted from 2008 through 2012. The trial compared
      participants in the intervention arm, who received an immediate educational
      curriculum (n = 166), to participants in the control arm, who received a delayed
      educational curriculum (n = 154). The home-based curriculum consisted of 5
      sessions led by community health workers and was designed to inform participants
      about diabetes, diabetes treatment, and healthy dietary and physical activity
      behaviors. Participants were randomly assigned to the intervention and control
      arms, and analysts were blinded as to participant arm. We evaluated intervention
      effects on HbA1c levels; frequency (times per week) of fruit and vegetable
      consumption; and frequency (times per week) of mild, moderate, and strenuous
      leisure-time physical activity. At baseline, 3 months, and 6 months after
      randomization, participants completed a questionnaire and provided a blood
      sample. Analysts were blinded to intervention arm. RESULTS: The immediate
      intervention group (-0.64% [standard error (SE) 0.10]) showed a significant
      improvement in HbA1c scores (-37.5%, P = .04) compared with the delayed
      intervention group (-0.44%, P = .14). No significant changes were seen for
      dietary end points or changes in physical activity. We did observe a trend of
      greater increases in frequency of moderate and vigorous physical activity and a
      smaller increase in mild physical activity in the immediate intervention group
      than in the delayed intervention group. CONCLUSION: This home-based intervention
      delivered by CHWs was associated with a clinically and statistically significant
      reduction in HbA1c levels in Hispanic adults with HbA1c levels higher than 6%.

PMID- 24576396
TI  - Challenges in meeting Healthy People 2020 objectives for cancer-related
      preventive services, National Health Interview Survey, 2008 and 2010.
AB  - INTRODUCTION: Healthy People (HP) is the US program that formulates and tracks
      national health objectives for the nation. The National Health Interview Survey
      (NHIS) is a designated data source for setting and evaluating several HP targets
      in cancer. We used data from the 2008 and 2010 NHIS to provide a benchmark for
      national performance toward meeting HP 2020 cancer-related objectives. METHODS:
      HP 2020 cancer screening, provider counseling, and health care access objectives
      were selected. For each objective, NHIS measures for the overall population and
      several sociodemographic subgroups were calculated; the findings were compared
      with established HP 2020 targets. RESULTS: From 2008 to 2010, rates of breast and
      cervical cancer screening declined slightly while colorectal cancer screening
      rates increased by 7 percentage points. Rates of cancer screening and provider
      counseling were below HP targets. Meeting HP targets seems less likely for
      subgroups characterized by low income, no health insurance, or no usual source of
      care. Meeting HP targets for access to health services will require an increase
      of 18 percentage points in the proportion of persons under age 65 with health
      insurance coverage and an increase of 10 percentage points in the proportion aged
      18 to 64 with a usual source of care. CONCLUSION: Whether HP objectives for
      cancer screening and health care access are met may depend on implementation of
      health care reform measures that improve access to and coordination of care.
      Better integration of clinical health care and community-based efforts for
      delivering high-quality screening and treatment services and elimination of
      health disparities are also needed.

PMID- 24576398
TI  - In situ determination and imaging of physical properties of soft organic
      materials by analytical transmission electron microscopy.
AB  - Analytical transmission electron microscopy (ATEM) offers great flexibility in
      identification of the structural-chemical organization of soft materials at the
      level of individual macromolecules. However, the determination of mechanical
      characteristics such as hardness/elasticity of the amorphous and polycrystalline
      organic substances by ATEM has been problematic so far. Here, we show that energy
      filtered TEM (EFTEM) measurements enable direct identification and study of
      mechanical properties in complex (bio-)polymer systems of relevance for different
      industrial and (bio-)medical applications. We experimentally demonstrate strong
      correlations between hardness/elasticity of different polymers (polycaprolactone,
      polylactid, polyethelene, etc.) and their volume plasmon energy. Thickness and
      anisotropy effects, which substantially mask the material contrast in EFTEM bulk
      plasmon images, can be adequately removed by normalizing the latter by carbon
      elemental map. EFTEM data has been validated using atomic force microscopy phase
      images, where phase shift related to the hardness and elastic modulus of the
      materials. 

PMID- 24576397
TI  - Association of painful musculoskeletal conditions and migraine headache with
      mental and sleep disorders among adults with disabilities, Spain, 2007-2008.
AB  - INTRODUCTION: The aim of this study was to determine the prevalence of painful
      musculoskeletal conditions and migraine headache or any other headache in a
      sample of Spanish adults with disabilities and their association with anxiety,
      depression, and sleep disorders. METHODS: This cross-sectional study analyzed
      data from the Spanish national disability and dependence survey (2007-2008) of
      16,932 adults aged 18 or older who have disabilities. The prevalence (95%
      confidence interval [CI]) of painful musculoskeletal conditions was determined
      according to a diagnosis of arthritis, osteoarthritis, rheumatoid arthritis,
      ankylosing spondylitis, muscular dystrophy, and neck or back pain. The prevalence
      of migraine or other headache was also calculated. Factors associated with these
      painful conditions were analyzed separately for men and women by using a logistic
      regression model. RESULTS: The prevalence of painful musculoskeletal conditions
      was 66.9% (95% CI, 66.2%-67.6%) and that of migraine or other headache was 23.4%
      (95% CI, 22.8%-24.1%), both of which were higher in women than in men. Factors
      associated with these conditions in both men and women included older age, a
      sleep disorder, and concomitant chronic anxiety and/or depression. CONCLUSION:
      The prevalence of painful musculoskeletal conditions and migraine or other
      headache is high in people with disability in Spain, especially in women, and
      these conditions often coexist with depression, anxiety, and/or a sleep disorder.
      To design programs for rehabilitating and improving the quality of life of adults
      with disability and painful conditions, treatments for mental and/or sleep
      disorders should be considered in addition to conventional treatments.

PMID- 24576399
TI  - Active immunisation against pregnenolone reduces testicular steroidogenesis and
      GnRH synthesis in rabbits.
AB  - To investigate the effects of active immunisation against pregnenolone on
      reproductive traits in rabbits, 16 early pubertal male rabbits (4mo old) were
      randomly and equally allocated into two groups, control or immunised against
      pregnenolone-hemisuccinate-BSA in Freund's adjuvant (with a booster 4wk later).
      Blood samples (for antibody titres and hormone concentrations) were collected at
      2 or 4wk-intervals after immunisation until rabbits were killed, 24wk after the
      primary immunisation. Compared to controls, rabbits immunised against
      pregnenolone had increased serum antibody titres (P<0.01) and decreased serum
      concentrations of both testosterone and LH (P<0.01 for each). At 24wk after the
      primary immunisation, testes were severely atrophied, spermatogenesis was
      arrested and steroidogenesis was suppressed, as evidenced by lesser amounts of
      testicular cholesterol side-chain cleavage cytochrome P-450 and 17alpha
      hydroxylase cytochrome P-450 mRNA (P<0.05). Furthermore, the amounts of mRNA for
      GnRH in the arcuate nucleus (Arc), of the hypothalamus and GnRH receptor and LH
      beta in the pituitary and genes in sex-hormone negative feedback loops (androgen
      receptor, oestrogen alpha receptor, kisspeptin encoded gene and kisspeptin
      receptor) in the Arc were decreased in pregnenolone-immunised rabbits compared to
      controls (P<0.05). It was concluded that immunisation against pregnenolone
      directly blocked testicular steroidogenesis, which reduced synthesis of
      hypothalamic GnRH and subsequently synthesis of pituitary LH by abolishing the
      permissive action of sex steroids on hypothalamic GnRH neurons, thereby
      disrupting spermatogenesis. This was apparently the first report that active
      immunisation against pregnenolone was a means of immunological castration. 

PMID- 24576400
TI  - Characterization of gametes in two phyllostomid bat species: Artibeus jamaicensis
      and Sturnira lilium.
AB  - Morphology of gametes is used to understand the physiological processes in
      reproduction among domestic and wild animals. These gametes are used in assisted
      reproductive technology (ART) and conservation programs. In the case of Artibeus
      jamaicensis and Sturnira lilium, few studies have been conducted related to these
      issues. The aim of this study was to describe the structure of spermatozoa, semen
      characteristics and also the morphology and quality of cumulus oocyte complexes
      (COC) of A. jamaicensis and S. lilium. Semen characteristics were: A. jamaicensis
      had a sperm concentration of 4.26*10(6)sperm/ml, progressive motility of 34.55%;
      viability of 73.23%; head, tail and mid-piece abnormalities of 12.50%. Head
      length was 6.26MUm, mid-piece 18.61MUm and tail 70.92MUm. S. lilium, had a sperm
      concentration of 5.15*10(6)sperm/ml, progressive motility of 60.00%, viability of
      83.82%; abnormalities in head, tail and mid-piece of 13.77%. Head length was
      7.01MUm, mid-piece 20.33MUm and tail 70.50MUm. On average 12.8 of right ovarian
      oocytes and 9.9 of left ovarian oocytes of A. jamaicensis were recovered. For S.
      lilium on average 10.7 oocytes from the right ovary and 10.9 oocytes from the
      left ovary were recovered, ranging in quality from excellent to poor. Sperm
      morphology and quality of COC were similar to those for other domestic and wild
      animals. Bat gametes can be used for the study of reproductive biology, in
      conservation programs and assisted reproductive technology (ART) among domestic
      and wild animals. 

PMID- 24576402
TI  - Clearing the smoke: what do we know about adolescent cannabis use and
      schizophrenia?

PMID- 24576403
TI  - Assessment of adult attention-deficit/hyperactivity disorder.

PMID- 24576401
TI  - Postprandial activation of metabolic and inflammatory signalling pathways in
      human peripheral mononuclear cells.
AB  - High-fat, high-carbohydrate (HFHC) meals induce an inflammatory response in
      mononuclear cells (MNC). Here, we studied the interaction between metabolic and
      inflammatory signalling pathways by the measurement of postprandial effects of
      three different test meals on intracellular Akt, S6 kinase (S6K)/mammalian target
      of rapamycin and NF-kappaB signalling in human MNC. We recruited six healthy,
      lean individuals. Each individual ingested three different meals in the morning
      separated by at least 3 d: a HFHC meal; an oral lipid-tolerance test meal; a
      healthy breakfast. Blood samples were obtained before and 1, 2, 4, 6 and 8 h
      after ingestion. Plasma insulin and IL-6 levels were measured. Intracellular
      metabolic and inflammatory signalling pathways were assessed by measuring the
      phosphorylation of Akt kinase and S6K, the degradation of inhibitory kappaB-alpha
      (IkappaB-alpha) protein and the DNA binding activity of NF-kappaB in MNC. mRNA
      expression levels of the Akt and NF-kappaB target genes Mn superoxide dismutase
      (MnSOD), CC-chemokine-receptor 5 (CCR5), intercellular adhesion molecule 1 (ICAM
      1) and plasminogen activator inhibitor-1 (PAI-1) were measured by quantitative RT
      PCR. We found a positive correlation of Akt phosphorylation with NF-kappaB
      activation (NF-kappaB binding activity: r 0.4500, P= 0.0003; IkappaB-alpha
      protein levels: r -0.5435, P< 0.0001), a negative correlation of plasma insulin
      levels with NF-kappaB binding activity (r -0.3993, P= 0.0016) and a positive
      correlation of plasma insulin levels with S6K activation (r 0.4786, P< 0.0001).
      The activation of Akt and pro-inflammatory NF-kappaB signalling was supported by
      the up-regulation of the respective target genes MnSOD and CCR5. In conclusion,
      the present data suggest a postprandial interaction between the metabolic and
      inflammatory signalling pathways Akt and NF-kappaB in MNC.

PMID- 24576405
TI  - Orientation precision of electron backscatter diffraction measurements near grain
      boundaries.
AB  - Electron backscatter diffraction (EBSD) has become a common technique for
      measuring crystallographic orientations at spatial resolutions on the order of
      tens of nanometers and at angular resolutions <0.1 degrees . In a recent search
      of EBSD papers using Google ScholarTM, 60% were found to address some aspect of
      deformation. Generally, deformation manifests itself in EBSD measurements by
      small local misorientations. An increase in the local misorientation is often
      observed near grain boundaries in deformed microstructures. This may be
      indicative of dislocation pile-up at the boundaries but could also be due to a
      loss of orientation precision in the EBSD measurements. When the electron beam is
      positioned at or near a grain boundary, the diffraction volume contains the
      crystal lattices from the two grains separated by the boundary. Thus, the
      resulting pattern will contain contributions from both lattices. Such mixed
      patterns can pose some challenge to the EBSD pattern band detection and indexing
      algorithms. Through analysis of experimental local misorientation data and
      simulated pattern mixing, this work shows that some of the rise in local
      misorientation is an artifact due to the mixed patterns at the boundary but that
      the rise due to physical phenomena is also observed.

PMID- 24576404
TI  - Identification of somatic mutations in EGFR/KRAS/ALK-negative lung adenocarcinoma
      in never-smokers.
AB  - BACKGROUND: Lung adenocarcinoma is a highly heterogeneous disease with various
      etiologies, prognoses, and responses to therapy. Although genome-scale
      characterization of lung adenocarcinoma has been performed, a comprehensive
      somatic mutation analysis of EGFR/KRAS/ALK-negative lung adenocarcinoma in never
      smokers has not been conducted. METHODS: We analyzed whole exome sequencing data
      from 16 EGFR/KRAS/ALK-negative lung adenocarcinomas and additional 54 tumors in
      two expansion cohort sets. Candidate loci were validated by target capture and
      Sanger sequencing. Gene set analysis was performed using Ingenuity Pathway
      Analysis. RESULTS: We identified 27 genes potentially implicated in the
      pathogenesis of lung adenocarcinoma. These included targetable genes involved in
      PI3K/mTOR signaling (TSC1, PIK3CA, AKT2) and receptor tyrosine kinase signaling
      (ERBB4) and genes not previously highlighted in lung adenocarcinomas, such as
      SETD2 and PBRM1 (chromatin remodeling), CHEK2 and CDC27 (cell cycle), CUL3 and
      SOD2 (oxidative stress), and CSMD3 and TFG (immune response). In the expansion
      cohort (N = 70), TP53 was the most frequently altered gene (11%), followed by
      SETD2 (6%), CSMD3 (6%), ERBB2 (6%), and CDH10 (4%). In pathway analysis, the
      majority of altered genes were involved in cell cycle/DNA repair (P <0.001) and
      cAMP-dependent protein kinase signaling (P <0.001). CONCLUSIONS: The genomic
      makeup of EGFR/KRAS/ALK-negative lung adenocarcinomas in never-smokers is
      remarkably diverse. Genes involved in cell cycle regulation/DNA repair are
      implicated in tumorigenesis and represent potential therapeutic targets.

PMID- 24576406
TI  - Antimycobacterial, anti-inflammatory and genotoxicity evaluation of plants used
      for the treatment of tuberculosis and related symptoms in South Africa.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Emergence of drug-resistant tuberculosis strains
      and long duration of treatment has established an urgent need to search for new
      effective agents. The great floral diversity of South Africa has potential for
      producing new bioactive compounds, therefore pharmacological screening of plant
      extracts within this region offers much potential. To assess the in vitro
      antimycobacterial, anti-inflammatory and genotoxicity activity of selected plants
      that are used for the treatment of TB and related symptoms in South Africa.
      MATERIALS AND METHODS: Ground plant materials from 10 plants were extracted
      sequentially with four solvents (petroleum ether, dichloromethane, 80% ethanol
      and water) and a total of 68 extracts were produced. A broth microdilution method
      was used to screen extracts against Mycobacterium tuberculosis H37Ra. The
      cyclooxygenase-2 (COX-2) enzyme was used to evaluate the anti-inflammatory
      activity of the extracts and the Salmonella microsome assay using two Salmonella
      typhimurium strains (TA98 and TA100) to establish genotoxicity. RESULTS: Six out
      of 68 extracts showed good antimycobacterial activity. Three extracts showed good
      inhibition (>70%) of COX-2 enzyme. All the extracts tested were non-genotoxic
      against the tested Salmonella strains. CONCLUSION: The results observed in this
      study indicate that some of the plants such as Abrus precatorius subsp.
      africanus, Ficus sur, Pentanisia prunelloides and Terminalia phanerophlebia could
      be investigated further against drug-resistant TB strains.

PMID- 24576407
TI  - Ethnoveterinary medicinal plants used by the Maale and Ari ethnic communities in
      southern Ethiopia.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Livestock production is an integral part of the
      agricultural system in Ethiopia. Medicinal plants are used and are important for
      rural communities for the treatment of livestock diseases. We studied and
      analysed the traditional medicinal plants used for the treatment of livestock
      diseases by the Maale and Ari ethnic communities in southern Ethiopia. MATERIALS
      AND METHODS: We used quantitative and qualitative ethobotanical methods,
      including individual and focus group discussions (n=18), field observations, and
      individual interviews (n=74) at three study sites. RESULTS: In total, 46 plant
      species (28 families) were used for the treatment of livestock diseases. Leaves
      with succulent stems were the most used part of the plant. The most frequently
      cited cattle disease was blackleg, for which 21 plant species were used. Our
      study showed variation in ethnoveterinary plant species used among sites
      (Jaccard's similarity indices <0.25). The number of medicinal plant species used
      was significantly influenced by gender and site. Knowledge on ethnoveterinary
      plants was predominantly held by males, who cited more plant uses than females.
      The most widely used species were Lepidium sativum, Allium sativum, Clausena
      anisata, Croton macrostachyus, Ozoroa insignis, Sida rhombifolia, Centella
      asiatica, Cissampelos mucronata, Vernonia theophrastifolia and Vernonia
      amygdalina. CONCLUSIONS: The study indicated that ethnoveterinary medicinal
      plants are important for the Maale and Ari ethnic communities. Phytochemical and
      pharmacological studies should focus on widely used and multi-use species.

PMID- 24576408
TI  - Acute toxicity study and effect of prolonged administration (28 days) of crude
      ethanolic root extract of Diospyros mespiliformis Hochst (Ebenaceae) on clinical,
      haematological and biochemical parameters of albino rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Different parts of the plant Diospyros
      mespiliformis have been used traditionally for the treatment of ailments in
      Nigeria particularly among the Kamwe people of Michika local government area of
      Adamawa State where the root has been used as an anti-malarial for ages. Most of
      the uses have been without any scientific evidence and toxicological assessment.
      The present study aimed to determine acute toxicity profile as well as the effect
      of prolonged administration of the extract on clinical, haematological and
      biochemical parameters of albino rats. MATERIALS AND METHODS: Thirty and twenty
      five Wistar rats of both sexes and of varying weights were, respectively, used
      for acute toxicity study and prolonged administration study of crude ethanolic
      root extract of Diospyros mespiliformis. The rats used for both studies were each
      administered graded concentrations of the extract (100, 200, 400, 800 and
      1600mg/kg) for acute toxicity testing and (50, 100, 200 and 400mg/kg) for the
      study of the effect of prolonged administration. The rats used for acute toxicity
      study were observed for a period of 24h for signs of toxicity and eventual death
      while parameters for prolonged study were recorded at weekly interval starting
      from day zero up to day 28 post administration. RESULTS: The extract produced an
      intraperitoneal LD50 of 570mg/kg. Body weight changes were not statistically
      significant (p>0.05) while haematological parameters (packed cell volume (PCV)),
      haemoglobin concentration (Hb), red blood cells (RBC), white blood cells (WBC)
      and differential leucocyte counts (DLC) were significantly modulated (p>0.05)
      after administration. Haematological indices (mean corpuscular volume (MCV)),
      mean corpuscular haemoglobin (MCH) and mean corpuscular haemoglobin
      concentrations (MCHC) were similarly modulated significantly (p>0.05).
      CONCLUSIONS: The extract appeared to be moderately toxic while prolonged
      administration improved the blood parameters of rats, suggesting that the plant's
      extract at lower doses can be used for a prolonged period, without deleterious
      effect on the haematological profile and serum enzymes.

PMID- 24576411
TI  - Fructose bisphosphate aldolase is involved in the control of RNA polymerase III
      directed transcription.
AB  - Yeast Fba1 (fructose 1,6-bisphosphate aldolase) is a glycolytic enzyme essential
      for viability. The overproduction of Fba1 enables overcoming of a severe growth
      defect caused by a missense mutation rpc128-1007 in a gene encoding the C128
      protein, the second largest subunit of the RNA polymerase III complex. The
      suppression of the growth phenotype by Fba1 is accompanied by enhanced de novo
      tRNA transcription in rpc128-1007 cells. We inactivated residues critical for the
      catalytic activity of Fba1. Overproduction of inactive aldolase still suppressed
      the rpc128-1007 phenotype, indicating that the function of this glycolytic enzyme
      in RNA polymerase III transcription is independent of its catalytic activity.
      Yeast Fba1 was determined to interact with the RNA polymerase III complex by
      coimmunoprecipitation. Additionally, a role of aldolase in control of tRNA
      transcription was confirmed by ChIP experiments. The results indicate a novel
      direct relationship between RNA polymerase III transcription and aldolase. 

PMID- 24576409
TI  - Mechanism of endoplasmic reticulum stress-induced vascular endothelial
      dysfunction.
AB  - BACKGROUND: We recently reported that ER stress plays a key role in vascular
      endothelial dysfunction during hypertension. In this study we aimed to elucidate
      the mechanisms by which ER stress induction and oxidative stress impair vascular
      endothelial function. METHODOLOGY/PRINCIPAL FINDINGS: We conducted in vitro
      studies with primary endothelial cells from coronary arteries stimulated with
      tunicamycin, 1MUg/mL, in the presence or absence of two ER stress inhibitors:
      tauroursodeoxycholic acid (Tudca), 500MUg/mL, and 4-phenylbutyric acid (PBA),
      5mM. ER stress induction was assessed by enhanced phosphorylation of PERK and
      eIF2alpha, and increased expression of CHOP, ATF6 and Grp78/Bip. The ER stress
      induction increased p38 MAPK phosphorylation, Nox2/4 mRNA levels and NADPH
      oxidase activity, and decreased eNOS promoter activity, eNOS expression and
      phosphorylation, and nitrite levels. Interestingly, the inhibition of p38 MAPK
      pathway reduced CHOP and Bip expressions enhanced by tunicamycin and restored
      eNOS promoter activation as well as phosphorylation. To study the effects of ER
      stress induction in vivo, we used C57BL/6J mice and p47phox(-/-) mice injected
      with tunicamycin or saline. The ER stress induction in mice significantly
      impaired vascular endothelium-dependent and independent relaxation in C57BL/6J
      mice compared with p47phox(-/-) mice indicating NADPH oxidase activity as an
      intermediate for ER stress in vascular endothelial dysfunction.
      CONCLUSION/SIGNIFICANCE: We conclude that chemically induced ER stress leads to a
      downstream enhancement of p38 MAPK and oxidative stress causing vascular
      endothelial dysfunction. Our results indicate that inhibition of ER stress could
      be a novel therapeutic strategy to attenuate vascular dysfunction during
      cardiovascular diseases.

PMID- 24576412
TI  - Ultra- and microstructure of the female reproductive system of Matsucoccus
      matsumurae.
AB  - The ultra- and microstructure of the female reproductive system of Matsucoccus
      matsumurae was studied using light microscopy, scanning and transmission electron
      microscopy. The results revealed that the female reproductive system of M.
      matsumurae is composed of a pair of ovaries, a common oviduct, a pair of lateral
      oviducts, a spermatheca and two pairs of accessory glands. Each ovary is composed
      of approximately 50 telotrophic ovarioles that are devoid of terminal filaments.
      Each ovariole is subdivided into an apical tropharium, a vitellarium and a short
      pedicel connected to a lateral oviduct. The tropharium contains 8-10 trophocytes
      and two early previtellogenic oocytes termed arrested oocytes. The trophocytes
      degenerate after egg maturation, and the arrested oocytes are capable of further
      development. The vitellarium contains 3-6 oocytes of different developmental
      stages: previtellogenesis, vitellogenesis and choriogenesis. The surface of the
      vitellarium is rough and composed of a pattern of polygonal reticular formations
      with a center protuberance. The oocyte possesses numerous yolk spheres and lipid
      droplets, and is surrounded by a mono-layered follicular epithelium that becomes
      binucleate at the beginning of vitellogenesis. Accessory nuclei are observed in
      the peripheral ooplasm during vitellogenesis.

PMID- 24576410
TI  - Specificity protein 4 (Sp4) regulates the transcription of AMPA receptor subunit
      GluA2 (Gria2).
AB  - The alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors are
      important glutamatergic receptors mediating fast excitatory synaptic transmission
      in the brain. The regulation of the four subunits of AMPA receptors, GluA1-4, is
      poorly understood. Excitatory synaptic transmission is highly energy-demanding,
      and this energy is derived mainly from the oxidative pathway. Recently, we found
      that specificity factor regulates all subunits of cytochrome c oxidase (COX), a
      critical energy-generating enzyme. COX is also regulated by nuclear respiratory
      factor 1 (NRF-1), which transcriptionally controls the Gria2 (GluA2) gene of AMPA
      receptors. The goal of the present study was to test our hypothesis that Sp
      factors (Sp1, Sp3, and/or Sp4) also regulate AMPA subunit genes. If so, we wish
      to determine if Sp-factors and NRF-1 function via a complementary, concurrent and
      parallel, or a combination of complementary and concurrent/parallel mechanism. By
      means of multiple approaches, including electrophoretic mobility shift and
      supershift assays, chromatin immunoprecipitation, promoter mutations, real-time
      quantitative PCR, and western blot analysis, we found that Sp4, but not Sp1 or
      Sp3, regulates the Gria2, but not Gria1, 3, or 4, subunit gene of the AMPA
      receptor in a concurrent and parallel manner with NRF-1. Thus, Sp4 and NRF-1 both
      mediate the tight coupling between neuronal activity and energy metabolism at the
      transcriptional level. 

PMID- 24576415
TI  - Role of 6-monoacetylmorphine in the acute release of striatal dopamine induced by
      intravenous heroin.
AB  - After injection, heroin is rapidly metabolized to 6-monoacetylmorphine (6-MAM)
      and further to morphine. As morphine has been shown to increase striatal
      dopamine, whereas 6-MAM has not been studied in this respect, we gave i.v.
      injections of 3 MUmol 6-MAM, morphine or heroin to rats. Opioids were measured in
      blood, and dopamine and opioids in microdialysate from brain striatal
      extracellular fluid (ECF), by UPLC-MS/MS. After 6-MAM injection, 6-MAM ECF
      concentrations increased rapidly, and reached Cmax of 4.4 MUM after 8 min. After
      heroin injection, 6-MAM increased rapidly in blood and reached Cmax of 6.4 MUM in
      ECF after 8 min, while ECF Cmax for heroin was 1.2 MUM after 2 min. T max for
      morphine in ECF was 29 and 24 min following 6-MAM and heroin administration,
      respectively, with corresponding Cmax levels of 1 and 2 MUM. Dopamine levels
      peaked after 8 and 14 min following 6-MAM and heroin administration,
      respectively. The dopamine responses were equal, indicating no dopamine release
      by heroin per se. Furthermore, 6-MAM, and not morphine, appeared to mediate the
      early dopamine response, whereas morphine administration, giving rise to morphine
      ECF concentrations similar to those observed shortly after 6-MAM injection, did
      not increase ECF dopamine. 6-MAM appeared accordingly to be the substance
      responsible for the early increase in dopamine observed after heroin injection.
      As 6-MAM was formed rapidly from heroin in blood, and was the major substance
      reaching the brain after heroin administration, this also indicates that factors
      influencing blood 6-MAM concentrations might change the behavioural effects of
      heroin.

PMID- 24576414
TI  - Optimal strategies for identifying kidney disease in diabetes: properties of
      screening tests, progression of renal dysfunction and impact of treatment -
      systematic review and modelling of progression and cost-effectiveness.
AB  - BACKGROUND: Annual screening for adults with type 2 diabetes to detect the early
      onset of kidney disease is widely recommended, but the recommendations are based
      on a limited methodological approach. In addition, there are continuing
      uncertainties about underlying rates of progression of the condition and the
      benefits of treatments with angiotensin-converting enzyme inhibitors and
      angiotensin receptor blockers. OBJECTIVES: We aimed to estimate the clinical
      value and cost-effectiveness of different screening intervals to diagnose early
      diabetic kidney disease. DATA SOURCES: We used the following databases for the
      literature review (searched January 2005 to August 2010): MEDLINE, EMBASE and the
      Cochrane Database of Systematic Reviews. Individual patient data were obtained
      from the Oxford Regional Prospective Diabetes Study and the Collaborative
      Atorvastatin Diabetes Study. METHODS: Data from systematically identified
      randomised trials reporting the impact on renal outcomes of angiotensin
      converting enzyme inhibitors and angiotensin 2 receptor blockers for type 1 and
      type 2 diabetes patients with normoalbuminuria and microalbuminuria were pooled
      to derive estimates of effect. Individual patient data for type 1 and type 2
      diabetes patients were used to obtain parameters describing progression and
      variability of measurement over time for the albumin-to-creatinine ratio (ACR)
      and estimated glomerular filtration rate. Based on accepted diagnostic
      thresholds, we modelled whether these tests accurately identified patients who
      were developing early diabetic kidney disease and required intensification of
      treatment. Cost-effectiveness analyses were carried out using simulation outcome
      models to estimate the incremental costs per quality-adjusted life-year (QALY)
      for different screening intervals. RESULTS: In total, 49 trials (n = 34,082
      patients) were eligible for inclusion in the systematic review. For type 1
      diabetes, pooled estimates of urinary albumin excretion (UAE) for treated
      patients with microalbuminuria were on average 67% [95% confidence interval (CI)
      54% to 77%] lower at the end of the trial than for untreated patients. There was
      no significant treatment effect for patients with normoalbuminuria (p interaction
      = 0.006). For treated patients with type 2 diabetes and normoalbuminuria or
      microalbuminuria, UAE was lower by, on average, 21% (95% CI 97% to 32%) or 27%
      (95% CI 15% to 38%), respectively. The proportion (95% CI) of men and women with
      type 1 diabetes screened annually for microalbuminuria over 6 years and
      inaccurately identified as having microalbuminuria would be 48% (43% to 53%) and
      55% (48% to 61%), respectively. The corresponding proportions for type 2 diabetes
      are 36% (32% to 42%) and 48% (41% to 55%). Decreasing the screening interval to 3
      yearly would reduce this for men with type 1 diabetes to 38% (33% to 44%), with
      an increase in those not identified over 6 years from 1.5% (95% CI 1% to 2%) to
      4% (95% CI 3% to 5%). For type 1 diabetes, incremental cost per QALY [standard
      deviation (SD)] of a 5-yearly compared with a 4-yearly screening interval was
      L3612 (L6586), increasing to L9601 (L34,112) for annual compared with 2-yearly
      screening. The probability that the intervention is cost saving is around 25%,
      and it has around an 80% chance of being below a cost-effectiveness threshold of
      L30,000. For type 2 diabetes, incremental cost per QALY (SD) of a yearly compared
      with a 2-yearly screening interval was L606 (L1782). The intervention is almost
      certainly below a cost-effectiveness threshold of L5000. CONCLUSIONS: These
      results support current UK guidance, which recommends annual screening with ACR
      to identify early kidney disease in patients with diabetes, despite a high false
      positive rate leading to, at worst, unnecessary or, at best, early therapeutic
      intervention. For type 1 diabetes, screening costs for annual compared with 2
      yearly screening are well within the bounds of accepted cost-effectiveness.
      Annual screening is even more cost-effective in type 2 diabetes than in type 1
      diabetes. Identification of alternative markers for developing diabetic
      nephropathy may improve targeting of treatment for those at high risk. FUNDING:
      The National Institute for Health Research Health Technology Assessment
      programme.

PMID- 24576417
TI  - Awareness of CKD in China: a national cross-sectional survey.

PMID- 24576418
TI  - Renegade homeostatic cytokine responses in T1D: drivers of regulatory/effector T
      cell imbalance.
AB  - Homeostatic cytokines contribute to the balance between regulatory and effector T
      cells (Tregs and Teffs respectively) and are necessary to maintain peripheral
      tolerance. These cytokines include IL-2 that supports Treg and IL-7 and IL-15
      that drive Teff. In overt settings of lost tolerance (i.e. graft rejection), IL-2
      Treg signatures are decreased while IL-7 and IL-15 Teff signatures are often
      enhanced. Similar cytokine profile imbalances also occur in some autoimmune
      diseases. In type 1 diabetes (T1D), there are underlying defects in the IL-2
      pathway and Teff cytokine blockade can prevent and treat diabetes in NOD mice. In
      this review, we summarize evidence of IL-2, IL-7 and IL-15 genetic and cellular
      alterations in T1D patients. We then discuss how the combined effect of these
      cytokine profiles may together contribute to altered Treg/Teff ratios and
      functions in T1D. Implications for combination therapies and suggestions for
      integrated cytokine and Treg/Teff biomarker development are then proposed. 

PMID- 24576416
TI  - Glucose and lipopolysaccharide regulate proatherogenic cytokine release from
      mononuclear cells in polycystic ovary syndrome.
AB  - Women with polycystic ovary syndrome (PCOS) have chronic low-grade inflammation,
      which can increase the risk of atherogenesis. We examined the effect of glucose
      ingestion and lipopolysaccharide (LPS) on markers of proatherogenic inflammation
      in the mononuclear cells (MNC) and plasma of women with PCOS. Sixteen women with
      PCOS (8 lean, 8 obese) and 15 weight-matched controls (8 lean, 7 obese) underwent
      a 3-h oral glucose tolerance test (OGTT). Interleukin-6 (IL-6) and interleukin
      1beta (IL-1beta) release from MNC cultured in the presence of LPS and plasma IL
      6, C-reactive protein (CRP), and soluble vascular adhesion molecule-1 (sVCAM-1)
      were measured from blood samples drawn while fasting and 2h after glucose
      ingestion. Truncal fat was measured by dual-energy absorptiometry (DEXA). Lean
      women with PCOS and obese controls failed to suppress LPS-stimulated IL-6 and IL
      1beta release from MNC after glucose ingestion. In contrast, obese women with
      PCOS suppressed these MNC-derived cytokines under the same conditions. In
      response to glucose ingestion, plasma IL-6 and sVCAM-1 increased and CRP
      suppression was attenuated in both PCOS groups and obese controls compared with
      lean controls. Fasting plasma IL-6 and CRP correlated positively with percentage
      of truncal fat. The absolute change in plasma IL-6 correlated positively with
      testosterone. We conclude that glucose ingestion promotes proatherogenic
      inflammation in PCOS with a systemic response that is independent of obesity.
      Based on the suppressed MNC-derived cytokine responses suggestive of LPS
      tolerance, chronic low-grade inflammation may be more profound in obese women
      with PCOS. Excess abdominal adiposity and hyperandrogenism may contribute to
      atherogenesis in PCOS. 

PMID- 24576419
TI  - C3 glomerulopathy: A new complement-based entity.
AB  - C3 glomerulopathy is a new, recently described entity that has changed the
      perspective, treatment and classification of a number of glomerular diseases. It
      encompasses 2 similar but clearly differentiated pathologies -the dense-deposit
      disease and C3 glomerulonephritis itself. The alternative complement pathway
      plays a fundamental role in its pathogenesis and, specifically, the mutations and
      defects in its regulatory factors (mainly factor H and factor I), as well as the
      presence of acquired autoantibodies (C3 nephritic factor), which generates an
      unbridled activation of the system, and ultimately, a deposit of its products at
      the glomerular level. Its poor prognosis and onset in young populations makes the
      detailed study of new therapeutic alternatives for this disease essential.
      Recently eculizumab, an anti-C5 antibody, has demonstrated effectiveness in the
      treatment of these patients.

PMID- 24576420
TI  - HEC of a job regulating stem cells.
AB  - In this issue of Developmental Cell, Schuster et al. (2014) describe the signals
      regulated by the bHLH transcription factor HEC1 during Arabidopsis stem cell
      maintenance. HEC1 acts antagonistically with other factors, integrating multiple
      cues to provide a balance between cellular differentiation and proliferation. 

PMID- 24576422
TI  - Developmental dynamics and disease potential of random monoallelic gene
      expression.
AB  - X chromosome inactivation (XCI) and allelic exclusion of olfactory receptors or
      immunoglobulin loci represent classic examples of random monoallelic expression
      (RME). RME of some single copy genes has also been reported, but the in vivo
      relevance of this remains unclear. Here we identify several hundred RME genes in
      clonal neural progenitor cell lines derived from embryonic stem cells. RME occurs
      during differentiation, and, once established, the monoallelic state can be
      highly stable. We show that monoallelic expression also occurs in vivo, in the
      absence of DNA sequence polymorphism. Several of the RME genes identified play
      important roles in development and have been implicated in human autosomal
      dominant disorders. We propose that monoallelic expression of such genes
      contributes to the fine-tuning of the developmental regulatory pathways they
      control, and, in the context of a mutation, RME can predispose to loss of
      function in a proportion of cells and thus contribute to disease.

PMID- 24576421
TI  - Random monoallelic gene expression increases upon embryonic stem cell
      differentiation.
AB  - Random autosomal monoallelic gene expression refers to the transcription of a
      gene from one of two homologous alleles. We assessed the dynamics of monoallelic
      expression during development through an allele-specific RNA-sequencing screen in
      clonal populations of hybrid mouse embryonic stem cells (ESCs) and neural
      progenitor cells (NPCs). We identified 67 and 376 inheritable autosomal random
      monoallelically expressed genes in ESCs and NPCs, respectively, a 5.6-fold
      increase upon differentiation. Although DNA methylation and nuclear positioning
      did not distinguish the active and inactive alleles, specific histone
      modifications were differentially enriched between the two alleles.
      Interestingly, expression levels of 8% of the monoallelically expressed genes
      remained similar between monoallelic and biallelic clones. These results support
      a model in which random monoallelic expression occurs stochastically during
      differentiation and, for some genes, is compensated for by the cell to maintain
      the required transcriptional output of these genes. 

PMID- 24576423
TI  - The GRIP1/14-3-3 pathway coordinates cargo trafficking and dendrite development.
AB  - Regulation of cargo transport via adaptor molecules is essential for neuronal
      development. However, the role of PDZ scaffolding proteins as adaptors in
      neuronal cargo trafficking is still poorly understood. Here, we show by genetic
      deletion in mice that the multi-PDZ domain scaffolding protein glutamate receptor
      interacting protein 1 (GRIP1) is required for dendrite development. We identify
      an interaction between GRIP1 and 14-3-3 proteins that is essential for the
      function of GRIP1 as an adaptor protein in dendritic cargo transport.
      Mechanistically, 14-3-3 binds to the kinesin-1 binding region in GRIP1 in a
      phospho-dependent manner and detaches GRIP1 from the kinesin-1 motor protein
      complex thereby regulating cargo transport. A single point mutation in the Thr956
      of GRIP1 in transgenic mice impairs dendritic development. Together, our results
      show a regulatory role for GRIP1 during microtubule-based transport and suggest a
      crucial function for 14-3-3 proteins in controlling kinesin-1 motor attachment
      during neuronal development. 

PMID- 24576425
TI  - Tight regulation of a timed nuclear import wave of EKLF by PKCtheta and FOE
      during Pro-E to Baso-E transition.
AB  - Erythropoiesis is a highly regulated process during which BFU-E are
      differentiated into RBCs through CFU-E, Pro-E, PolyCh-E, OrthoCh-E, and
      reticulocyte stages. Uniquely, most erythroid-specific genes are activated during
      the Pro-E to Baso-E transition. We show that a wave of nuclear import of the
      erythroid-specific transcription factor EKLF occurs during the Pro-E to Baso-E
      transition. We further demonstrate that this wave results from a series of finely
      tuned events, including timed activation of PKCtheta, phosphorylation of EKLF at
      S68 by P-PKCtheta(S676), and sumoylation of EKLF at K74. The latter EKLF
      modifications modulate its interactions with a cytoplasmic ankyrin-repeat-protein
      FOE and importinbeta1, respectively. The role of FOE in the control of EKLF
      nuclear import is further supported by analysis of the subcellular distribution
      patterns of EKLF in FOE-knockout mice. This study reveals the regulatory
      mechanisms of the nuclear import of EKLF, which may also be utilized in the
      nuclear import of other factors. 

PMID- 24576424
TI  - Enabled negatively regulates diaphanous-driven actin dynamics in vitro and in
      vivo.
AB  - Actin regulators facilitate cell migration by controlling cell protrusion
      architecture and dynamics. As the behavior of individual actin regulators becomes
      clear, we must address why cells require multiple regulators with similar
      functions and how they cooperate to create diverse protrusions. We characterized
      Diaphanous (Dia) and Enabled (Ena) as a model, using complementary approaches:
      cell culture, biophysical analysis, and Drosophila morphogenesis. We found that
      Dia and Ena have distinct biochemical properties that contribute to the different
      protrusion morphologies each induces. Dia is a more processive, faster elongator,
      paralleling the long, stable filopodia it induces in vivo, while Ena promotes
      filopodia with more dynamic changes in number, length, and lifetime. Acting
      together, Ena and Dia induce protrusions distinct from those induced by either
      alone, with Ena reducing Dia-driven protrusion length and number. Consistent with
      this, EnaEVH1 binds Dia directly and inhibits DiaFH1FH2-mediated nucleation in
      vitro. Finally, Ena rescues hemocyte migration defects caused by activated Dia.

PMID- 24576426
TI  - A regulatory framework for shoot stem cell control integrating metabolic,
      transcriptional, and phytohormone signals.
AB  - Plants continuously maintain pluripotent stem cells embedded in specialized
      tissues called meristems, which drive long-term growth and organogenesis. Stem
      cell fate in the shoot apical meristem (SAM) is controlled by the homeodomain
      transcription factor WUSCHEL (WUS) expressed in the niche adjacent to the stem
      cells. Here, we demonstrate that the bHLH transcription factor HECATE1 (HEC1) is
      a target of WUS and that it contributes to SAM function by promoting stem cell
      proliferation, while antagonizing niche cell activity. HEC1 represses the stem
      cell regulators WUS and CLAVATA3 (CLV3) and, like WUS, controls genes with
      functions in metabolism and hormone signaling. Among the targets shared by HEC1
      and WUS are phytohormone response regulators, which we show to act as mobile
      signals in a universal feedback system. Thus, our work sheds light on the
      mechanisms guiding meristem function and suggests that the underlying regulatory
      system is far more complex than previously anticipated. 

PMID- 24576428
TI  - International Ear Care Day--3rd March.

PMID- 24576429
TI  - Four polymorphisms of the pericentriolar material 1 (PCM1) gene are not
      associated with schizophrenia in a Japanese population.

PMID- 24576427
TI  - A regulatory network of Drosophila germline stem cell self-renewal.
AB  - Stem cells possess the capacity to generate two cells of distinct fate upon
      division: one cell retaining stem cell identity and the other cell destined to
      differentiate. These cell fates are established by cell-type-specific genetic
      networks. To comprehensively identify components of these networks, we performed
      a large-scale RNAi screen in Drosophila female germline stem cells (GSCs)
      covering ~25% of the genome. The screen identified 366 genes that affect GSC
      maintenance, differentiation, or other processes involved in oogenesis.
      Comparison of GSC regulators with neural stem cell self-renewal factors
      identifies common and cell-type-specific self-renewal genes. Importantly, we
      identify the histone methyltransferase Set1 as a GSC-specific self-renewal
      factor. Loss of Set1 in neural stem cells does not affect cell fate decisions,
      suggesting a differential requirement of H3K4me3 in different stem cell lineages.
      Altogether, our study provides a resource that will help to further dissect the
      networks underlying stem cell self-renewal. 

PMID- 24576430
TI  - The influence of patient sex, provider sex, and sexist attitudes on pain
      treatment decisions.
AB  - Research suggests that patient sex, provider sex, and providers' sexist attitudes
      interact to influence pain care; however, few empirical studies have examined
      these influences. We investigated sex (patient and provider) differences in pain
      treatment and the extent to which providers' sexist attitudes were associated
      with these differences. Ninety-eight health care providers (52% female) completed
      the Ambivalent Sexism Inventory and made treatment ratings for 16 computer
      simulated patients with low back pain. Patient sex was balanced across vignettes.
      Results indicated that female patients received significantly higher
      antidepressant (F[1, 96] = 4.51, P < .05, etap(2) = .05) and mental health
      referral (F[1, 96] = 3.89, P = .05, etap(2) = .04) ratings than male patients,
      which is consistent with our hypotheses; however, these differences were
      significant only among female providers. Controlling for providers' sexism scores
      did not substantially alter these results, which is counter to our hypotheses.
      These results suggest that female providers are more likely to recommend
      psychosocial treatments for female than for male pain patients, and providers'
      sexist attitudes do not account for these differences. Research is needed to
      elucidate the contributors to sex/gender differences in treatment in order to
      reduce pain disparities. PERSPECTIVE: The results of this study suggest that
      patient and provider sex, but not providers' sexist attitudes, influence pain
      care. These findings may inform efforts to raise awareness of sex/gender
      differences in pain care and reduce disparities.

PMID- 24576431
TI  - Clinical spectrum of isolated left ventricular noncompaction: thromboembolic
      events, malignant left ventricular arrhythmias, and refractory heart failure.

PMID- 24576433
TI  - Enhanced activity of ADP glucose pyrophosphorylase and formation of starch
      induced by Azospirillum brasilense in Chlorella vulgaris.
AB  - ADP-glucose pyrophosphorylase (AGPase) regulates starch biosynthesis in higher
      plants and microalgae. This study measured the effect of the bacterium
      Azospirillum brasilense on AGPase activity in the freshwater microalga Chlorella
      vulgaris and formation of starch. This was done by immobilizing both
      microorganisms in alginate beads, either replete with or deprived of nitrogen or
      phosphorus and all under heterotrophic conditions, using d-glucose or Na-acetate
      as the carbon source. AGPase activity during the first 72h of incubation was
      higher in C. vulgaris when immobilized with A. brasilense. This happened
      simultaneously with higher starch accumulation and higher carbon uptake by the
      microalgae. Either carbon source had similar effects on enzyme activity and
      starch accumulation. Starvation either by N or P had the same pattern on AGPase
      activity and starch accumulation. Under replete conditions, the population of C.
      vulgaris immobilized alone was higher than when immobilized together, but under
      starvation conditions A. brasilense induced a larger population of C. vulgaris.
      In summary, adding A. brasilense enhanced AGPase activity, starch formation, and
      mitigation of stress in C. vulgaris. 

PMID- 24576432
TI  - Survival effects of inferior vena cava filter in patients with acute symptomatic
      venous thromboembolism and a significant bleeding risk.
AB  - OBJECTIVES: The purpose of this study was to investigate the survival effects of
      inferior vena cava filters in patients with venous thromboembolism (VTE) who had
      a significant bleeding risk. BACKGROUND: The effectiveness of inferior vena cava
      filter use among patients with acute symptomatic VTE and known significant
      bleeding risk remains unclear. METHODS: In this prospective cohort study of
      patients with acute VTE identified from the RIETE (Computerized Registry of
      Patients With Venous Thromboembolism), we assessed the association between
      inferior vena cava filter insertion for known significant bleeding risk and the
      outcomes of all-cause mortality, pulmonary embolism (PE)-related mortality, and
      VTE rates through 30 days after the initiation of VTE treatment. Propensity score
      matching was used to adjust for the likelihood of receiving a filter. RESULTS: Of
      the 40,142 eligible patients who had acute symptomatic VTE, 371 underwent filter
      placement because of known significant bleeding risk. A total of 344 patients
      treated with a filter were matched with 344 patients treated without a filter.
      Propensity score-matched pairs showed a nonsignificant trend toward lower risk of
      all-cause death for filter insertion compared with no insertion (6.6% vs. 10.2%;
      p = 0.12). The risk-adjusted PE-related mortality rate was lower for filter
      insertion than no insertion (1.7% vs. 4.9%; p = 0.03). Risk-adjusted recurrent
      VTE rates were higher for filter insertion than for no insertion (6.1% vs. 0.6%;
      p < 0.001). CONCLUSIONS: In patients presenting with VTE and with a significant
      bleeding risk, inferior vena cava filter insertion compared with anticoagulant
      therapy was associated with a lower risk of PE-related death and a higher risk of
      recurrent VTE. However, study design limitations do not imply a causal
      relationship between filter insertion and outcome.

PMID- 24576434
TI  - Unfamiliar metabolic links in the central carbon metabolism.
AB  - The central carbon metabolism of all organisms is considered to follow a well
      established fixed scheme. However, recent studies of autotrophic carbon fixation
      in prokaryotes revealed unfamiliar metabolic links. A new route interconnects
      acetyl-coenzyme A (CoA) via 3-hydroxypropionate with succinyl-CoA. Succinyl-CoA
      in turn may be metabolized via 4-hydroxybutyrate to two molecules of acetyl-CoA;
      a reversal of this route would result in the assimilation of two molecules of
      acetyl-CoA into C4 compounds. C5-dicarboxylic acids are a rather neglected class
      of metabolites; yet, they play a key role not only in one of the CO2 fixation
      cycles, but also in two acetate assimilation pathways that replace the glyoxylate
      cycle. C5 compounds such as ethylmalonate, methylsuccinate, methylmalate,
      mesaconate, itaconate and citramalate or their CoA esters are thereby linked to
      the acetyl-CoA, propionyl-CoA, glyoxylate and pyruvate pools. A novel
      carboxylase/reductase converts crotonyl-CoA into ethylmalonyl-CoA; similar
      reductive carboxylations apply to other alpha-beta-unsaturated carboxy-CoA
      thioesters. These unfamiliar metabolic links may provide useful tools for
      metabolic engineering. 

PMID- 24576435
TI  - Sperm survival kinetics in different types of bull semen: progressive motility,
      plasma membrane integrity, acrosomal status and reactive oxygen species
      generation.
AB  - This study was designed to compare the kinetics of sperm survival in different
      types of bull semen. Fresh ejaculates from four bulls were pooled, diluted in
      Tris-citric acid-egg yolk-glycerol extender, cooled to 4 degrees C, frozen in LN2
      and thawed at 37 degrees C. Fresh, diluted, cooled and frozen-thawed semen were
      incubated at 37 degrees C, and evaluated at 0, 2, 4, 6, 12 and 24h after the
      beginning of incubation. In Experiment 1, progressive sperm motility, normal
      acrosomes and plasma membrane integrity and asymmetry were determined. In
      Experiment 2, generation of superoxide anion (O2(*)) along with plasma membrane
      permeability and generation of hydrogen peroxide (H2O2) along with plasma
      membrane integrity were assessed. In Experiment 1, frozen-thawed semen had
      shorter survival times for progressive sperm motility, and spermatozoa with
      intact plasma membranes and acrosomes (IPM-IACR) as compared with other types of
      semen (P<0.05). Fresh spermatozoa underwent a necrotic pathway, diluted and
      cooled spermatozoa underwent an apoptosis-like pathway and frozen-thawed
      spermatozoa underwent both necrotic and apoptosis-like pathways. In Experiment 2,
      spermatozoa in all four types of semen exhibited O2(*-) generation and increased
      plasma membrane permeability, and became necrotic without H2O2 generation during
      incubation (P<0.05). In conclusion, frozen-thawed semen had shorter sperm
      longevity, which has important implications relating to the timing of artificial
      insemination. Different types of semen followed different death pathways. During
      incubation, spermatozoa in all types of semen generated O2(*-), which increased
      the permeability and compromised the integrity of the plasma membrane. 

PMID- 24576437
TI  - Does decompression of odontogenic cysts and cystlike lesions change the
      histologic diagnosis?
AB  - PURPOSE: The purpose of this study was to report the histopathologic findings
      after postdecompression definitive treatment of odontogenic cystlike lesions and
      determine whether the diagnosis was consistent with the pretreatment diagnosis,
      thereby answering the clinical question: does decompression change the histologic
      diagnosis? MATERIALS AND METHODS: The authors implemented a retrospective cohort
      study from a sample of patients diagnosed with a benign odontogenic cystlike
      lesion and who underwent decompression followed by definitive surgery as part of
      their treatment. The predictor variable was treatment by decompression and the
      dependent variable was change in histologic diagnosis. Age, gender, and lesion
      location were included as variables. The chi(2) test was used for statistical
      analysis of the categorical data and P values less than .05 were considered
      statistically significant. RESULTS: Twenty-five cysts and cystlike lesions in 25
      patients were treated with decompression followed by enucleation and curettage.
      The mean age was 34 years (range, 13 to 80 yr) and 56% (14) were male patients.
      Lesions were located in the mandible in 76% (19 of 25) of patients.
      Postdecompression histologic examination at the time of definitive surgical
      treatment was consistent with the preoperative biopsy diagnosis in 91% (10 of 11)
      of keratocystic odontogenic tumors, 67% (2 of 3) of glandular odontogenic cysts,
      75% (3 of 4) of dentigerous cysts, and 100% (7 of 7) of cystic ameloblastomas.
      CONCLUSIONS: The histologic diagnosis at time of definitive treatment by
      enucleation and curettage is consistent with the predecompression diagnosis.
      Therefore, all lesions should be definitively treated after decompression based
      on the initial lesion diagnosis, with all patients placed on appropriate follow
      up protocols.

PMID- 24576436
TI  - A rare case of undifferentiated nonkeratinizing carcinoma of the lip mucosa.
AB  - Undifferentiated nonkeratinizing carcinoma (UNC) is a poorly differentiated
      squamous cell carcinoma accompanied by a prominent reactive lymphoplasmacytic
      infiltrate that can occur in many anatomic sites. It shares morphologic features
      with undifferentiated nonkeratinizing nasopharyngeal carcinoma, in which a strong
      association with Epstein-Barr virus (EBV) has been noted. Among UNCs arising
      outside the nasopharynx, the linkage with EBV is variable; in particular, the few
      cases of UNC of the lip described thus far have been negative for EBV. This
      report describes a rare case of primary UNC of the lower lip mucosa in a 73-year
      old man in whom molecular analysis for EBV showed some amount of viral DNA within
      the tumor. Surgical excision without adjuvant treatment was performed and the
      patient was alive without recurrence after 42 months of follow-up. This report
      presents a rare localization of UNC possibly related to EBV infection and with a
      good clinical outcome.

PMID- 24576438
TI  - Comparison of tissue-engineered bone from different stem cell sources for
      maxillary sinus floor augmentation: a study in a canine model.
AB  - PURPOSE: To compare the potential of tissue-engineered bone derived from
      different stem cell sources for canine maxillary sinus augmentation. MATERIALS
      AND METHODS: Bilateral maxillary sinus floor augmentations were performed in 6
      beagles and were randomly repaired with 3 graft types: Bio-Oss granules alone (n
      = 4; group A), a complex of osteoblasts derived from bone marrow mesenchymal stem
      cells (BMMSCs) and Bio-Oss (n = 4; group B), and a complex of osteoblasts derived
      from periodontal ligament stem cells (PDLSCs) and Bio-Oss (n = 4; group C). After
      12 weeks, fluorescent labeling, maxillofacial computed tomography, scanning
      electron microscopy, and histologic and histomorphometric analyses were used to
      evaluate new bone deposition, mineralization, and remodeling in the augmented
      area. RESULTS: The osteogenic capacity was greater in groups B and C than in
      group A. The level tended to be higher in group C than in group B; however, the
      difference was not statistically significant. CONCLUSIONS: Seeding of PDLSCs or
      BMMSCs onto Bio-Oss can promote bone formation and mineralization and maintain
      the maximum volume of the augmented maxillary sinus. These tissue-engineered bone
      complexes might be a good option for augmentation of the maxillary sinus in
      edentulous patients.

PMID- 24576439
TI  - Zygomatic implants for the management of the severely atrophied maxilla: a
      retrospective analysis of 244 implants.
AB  - PURPOSE: The aim of this investigation was to describe the surgical techniques,
      success rate, prosthetic rehabilitation, complications, and demographics of
      patients undergoing zygomatic implant surgery. PATIENTS AND METHODS: A
      retrospective case series study design was implemented that included patients who
      received zygomatic implants identified in the database of the Department of Oral
      and Maxillofacial Surgery, Universidad El Bosque from 2009 to 2013. Contact
      information was retrieved from the charts and patients were asked to attend the
      department for a follow-up appointment. The population consisted of all patients
      found in the database and the sample included otherwise healthy patients living
      in Bogota, Colombia. Predictor variables were categorized into patient's medical
      history, demographics, surgical technique, and prosthetic rehabilitation. The
      outcome variable was the presence or absence of postoperative complications.
      Smokers, diabetics, and patients living outside Bogota were excluded. Patients
      also were excluded if their medical status had changed since zygomatic implant
      surgery. Descriptive statistics were computed for each study variable. RESULTS:
      Data of 95 patients were retrieved. The sample consisted of 80 patients in whom
      244 implants were inserted. The sample's mean age was 55.5 years. One hundred
      eleven zygomatic implants were placed in women and 133 were placed in men, with
      an overall complication rate of 9.9%, with sinusitis the most frequent
      complication (7.5%). Other complications included paresthesia (0.4%) and
      oroantral fistula (0.4%). The follow-up period was 6 to 48 months. CONCLUSIONS:
      This investigation reviewed the authors' 4-year experience placing zygomatic
      implants and proved a reliable method for the treatment of the resorbed maxilla.

PMID- 24576440
TI  - Therapeutic effects of local application of dexamethasone during bilateral
      sagittal split ramus osteotomy surgery.
AB  - PURPOSE: Bilateral sagittal split ramus osteotomy (BSSO) is one of the most
      common procedures used in the treatment of mandibular deformity. One common
      complication of this surgical procedure is hypoesthesia of the inferior alveolar
      nerve. The authors hypothesized that perioperative local application of
      dexamethasone would have positive therapeutic effects on neurosensory function.
      MATERIALS AND METHODS: This study investigated 18 patients (10 male, 8 female;
      mean age, 26.1 +/- 4.9 yr) who underwent BSSO. One side of each patient's
      mandible was randomly selected as the control side and the opposite side as the
      experimental side. A solution of dexamethasone 4 mg/1 mL was drawn into a syringe
      and poured directly on the distal segment of the exposed inferior alveolar nerve
      during splitting and 1 mL was poured on the same nerve immediately before the
      start of fixation. Neurosensory tests, including light touch, direction of
      movement, static 2-point touch, thermal stimuli, and pin prick discrimination,
      were conducted. The chi(2) and Fisher exact tests were used to evaluate the data.
      RESULTS: The difference between the control and experimental groups at all
      intervals was not significant for any of the neurosensory tests. CONCLUSION:
      Local application of dexamethasone on the exposed inferior alveolar nerve during
      BSSO is not recommended.

PMID- 24576441
TI  - The need for palliative care education, support, and reflection among rural
      nurses and other staff: A quantitative study.
AB  - OBJECTIVE: Many people now die in community care, and, considering the aging
      population, all healthcare staff members must be prepared to provide palliative
      care. Our objectives were to describe the total staff working in different care
      organizations in a rural community in Sweden and to explore palliative care
      competence, to describe educational gaps and the need for support and reflection,
      and to determine whether there are differences in care organizations,
      professions, age, and gender. METHOD: A 4-section 20-item questionnaire was
      distributed to 1686 staff (65% response rate): in nursing homes (n = 395), home
      care (n = 240), and group residential settings (n = 365). Registered nurses (n =
      70), assistant nurses (n = 916), managers (n = 43), and paramedics (n = 33)
      participated. Descriptive and correlational statistics were employed. RESULTS:
      Significant differences were found, and 40% (53% among men) lacked palliative
      care education, Fewer than 50% lacked education in the spiritual/existential
      areas, and 75% of those aged 20-66 (75% women, 55% men) needed further education.
      More women than men and staff aged 50-59 had an increased need to reflect.
      SIGNIFICANCE OF RESULTS: Our study may provide guidance for managers in rural
      communities when planning educational interventions in palliative care for
      healthcare staff and may support direct education with content for specific
      professions.

PMID- 24576442
TI  - Coughing up blood: Behcet's disease.

PMID- 24576443
TI  - Effect of hexavalent chromium on proliferation and differentiation to adipocytes
      of 3T3-L1 fibroblasts.
AB  - Heavy metals contamination has become an important risk factor for public health
      and the environment. Chromium is a frequent industrial contaminant and is also
      used in orthopaedic joint replacements made from cobalt-chromium-alloy. Since
      hexavalent chromium (Cr(VI)) was reported as genotoxic and carcinogenic in
      different mammals, to further evaluate its cytotoxicity, we investigated the
      effect of this heavy metal in the proliferation and differentiation to adipocytes
      of 3T3-L1 fibroblasts. These cells, after the addition of a mixture containing
      insulin, dexamethasone and methylisobutylxanthine, first proliferate, a process
      known as mitotic clonal expansion (MCE), and then differentiate to adipocytes. In
      this differentiation process a key transcription factor is induced: peroxisome
      proliferator-activated receptor gamma (PPAR gamma). We found that treatment of
      3T3-L1 fibroblasts with potassium chromate inhibited proliferation in
      exponentially growing cells and MCE as well as differentiation. A decrease in
      PPAR gamma content, evaluated by western blot and immunofluorescence, was found
      in cells differentiated in the presence of chromium. On the other hand, after
      inhibition of differentiation with chromium, when the metal was removed,
      differentiation was recovered, which indicates that this may be a reversible
      effect. We also found an increase in the number of micronucleated cells after
      treatment with Cr(VI) which is associated with genotoxic effects. According to
      our results, Cr(VI) is able to inhibit proliferation and differentiation to
      adipocytes of 3T3-L1 fibroblasts and to increase micronucleated cells, which are
      all indicative of alterations in cellular physiology and therefore, contributes
      to further elucidate the cytotoxic effects of this heavy metal. 

PMID- 24576444
TI  - Measuring the effect of avermectins and milbemycins on somatic muscle contraction
      of adult Haemonchus contortus and on motility of Ostertagia circumcincta in
      vitro.
AB  - The mechanism of anthelmintic resistance against the widely used macrocyclic
      lactones (MLs) is still not fully understood. Pharyngeal, somatic body muscles
      and the ovijector have been proposed as putative sites of action as well as
      resistance. In the present study the effects of three avermectins and three
      milbemycins on adult parasitic nematodes were evaluated in vitro. The Muscle
      Transducer system was used to investigate the effects of MLs on muscle
      contraction in female Haemonchus contortus and effects on motility were measured
      in Ostertagia (Teladorsagia) circumcincta using the Micromotility Meter.
      Concentration-response curves for all substances in both systems shifted to the
      right in the resistant isolates. Resistance was present to ivermectin (IVM) and
      its components IVM B1a and IVM B1b, suggesting that both components are involved
      in the mode of action and resistance. No consistent patterns of potency and
      resistance of the substances were observed except that milbemycins generally
      showed lower resistance ratios (RRs) than IVM. IVM and IVM B1b were the most
      potent inhibitors of contraction and motility in both susceptible isolates and
      also showed the highest RR in both species. Low RRs for milbemycins recorded in
      vitro for highly resistant isolates in vivo suggest that other factors such as
      pharmacokinetics influence drug potency in vivo.

PMID- 24576445
TI  - Engineering Xenopus embryos for phenotypic drug discovery screening.
AB  - Many rare human inherited diseases remain untreatable despite the fact that the
      disease causing genes are known and adequate mouse disease models have been
      developed. In vivo phenotypic drug screening relies on isolating drug candidates
      by their ability to produce a desired therapeutic phenotype in whole organisms.
      Embryos of zebrafish and Xenopus frogs are abundant, small and free-living. They
      can be easily arrayed in multi-well dishes and treated with small organic
      molecules. With the development of novel genome modification tools, such a zinc
      finger nucleases (ZFNs), transcription activator-like effector nucleases
      (TALENs), and CRISPR/Cas, it is now possible to efficiently engineer non
      mammalian models of inherited human diseases. Here, we will review the rapid
      progress made in adapting these novel genome editing tools to Xenopus. The
      advantages of Xenopus embryos as in vivo models to study human inherited diseases
      will be presented and their utility for drug discovery screening will be
      discussed. Being a tetrapod, Xenopus complements zebrafish as an indispensable
      non-mammalian animal model for the study of human disease pathologies and the
      discovery of novel therapeutics for inherited diseases.

PMID- 24576446
TI  - Clinical education in nursing: rethinking learning in practice settings.
AB  - Clinical education is a time- and resource-intensive aspect of contemporary
      nursing programs. Despite widespread agreement in the discipline about the
      centrality of clinical experiences to learning nursing, little is known about if
      and how current clinical experiences contribute to students' learning and
      readiness for practice. Before large-scale studies testing specific educational
      interventionals can be conducted, it is important to understand what currently
      occurs during clinical experiences. This study, funded by the National Council of
      State Boards of Nursing, examined the nature of contemporary clinical education
      by describing students' and faculty's experiences at three geographically diverse
      universities in the United States. Findings suggest that teachers' and students'
      focus on task completion persists and often overshadows the more complex aspects
      of learning nursing practice. 

PMID- 24576448
TI  - Recurrent pneumonia due to bronchial carcinoid tumour in a young patient: the
      role of (111)in-pentetreotide in imaging studies.
AB  - Bronchial carcinoid tumours are an uncommon cause of recurrent pneumonia in young
      patients. Diagnosis is determined from imaging studies, bronchoscopy, and
      histological confirmation, and treatment is generally surgical. Two cases are
      reviewed in order to examine the value of (111)In-DTPA-Phe-octreotide ((111)In
      pentetreotide) scintigraphy in the pre-surgical evaluation of these patients.
      After a suspicious area was observed in other tests (standard X-ray, CT), a
      neuroendocrine tumour was diagnosed using this technique and the presence of
      regional or distant disease was ruled out. Comparison with the less valuable
      (18)F-FDG PET (carried out in one of the cases) highlights the usefulness of
      SPECT-CT, which performs notably better in terms of the localization and
      characterisation of findings. 

PMID- 24576447
TI  - Tru-cut needle pleural biopsy and cytology as the initial procedure in the
      evaluation of pleural effusion.
AB  - INTRODUCTION AND OBJECTIVES: The evaluation of pleural effusion (PE) includes
      various techniques, including pleural biopsy (PB). Our aim was to study the
      diagnostic yield of Tru-Cut needle PB (TCPB) and to define clinical/radiological
      situations in which TCPB might be indicated as an initial procedure. METHODOLOGY:
      Retrospective study of TCPB in a hospital centre (2010-2012). Cases of pleural
      lesions without effusion were excluded. Clinical and radiological variables,
      diagnostic yield, TCPB complications and factors associated with the diagnostic
      yield of the combination of TCPB and thoracocentesis as initial procedure were
      analysed. RESULTS: One hundred and twenty-seven (127) TCPB were reviewed: 29.1%
      were cases of malignant PE and in 18.9% the cause of the PE could not be
      determined. The diagnostic yield of TCPB for tuberculosis was 76.5% (13/17) and
      54% (20/37) for malignant PE. Complications occurred in 4.7% of the cases. In 72
      patients with a final definitive diagnosis, TCPB was performed at the same time
      as the initial thoracocentesis. Diagnostic yield for the combination of
      TCPB/cytology as an initial technique was 43% (31/72) compared to 12.5% (9/72)
      for cytology only (p=0.01). The only predictive variable for the indication of
      TCBP as an initial technique was a PE volume>2/3 (P=.04). CONCLUSIONS: TCPB is
      safe and provides an acceptable diagnostic yield, particularly when combined with
      simultaneous cytology in the evaluation of PE of various aetiologies.
      Radiological criteria may help guide the selection of patients who could benefit
      from this technique as an initial procedure combined with thoracocentesis.

PMID- 24576449
TI  - Distribution of clinical phenotypes in patients with chronic obstructive
      pulmonary disease caused by biomass and tobacco smoke.
AB  - INTRODUCTION: Exposure to biomass smoke is a risk factor for chronic obstructive
      pulmonary disease (COPD). It is unknown whether COPD caused by biomass smoke has
      different characteristics to COPD caused by tobacco smoke. OBJECTIVE: To
      determine clinical differences between these two types of the disease. METHODS:
      Retrospective observational study of 499 patients with a diagnosis of COPD due to
      biomass or tobacco smoke. The clinical variables of both groups were compared.
      RESULTS: There were 122 subjects (24.4%) in the biomass smoke group and 377
      (75.5%) in the tobacco smoke group. In the tobacco group, the percentage of males
      was higher (91.2% vs 41.8%, P<.0001) and the age was lower (70.6 vs 76.2 years,
      P<.0001). Body mass index and FEV1% values were higher in the biomass group
      (29.4+/-5.7 vs 28.0+/-5.1, P=.01, and 55.6+/-15.6 vs 47.1+/-17.1, P<.0001,
      respectively). The mixed COPD-asthma phenotype was more common in the biomass
      group (21.3% vs 5%, P<.0001), although this difference disappeared when corrected
      for gender. The emphysema phenotype was more common in the tobacco group (45.9%
      vs 31.9%, P=.009). The prevalence of the chronic bronchitis and exacerbator
      phenotypes, the comorbidity burden and the rate of hospital admissions were the
      same in both groups. CONCLUSION: Differences were observed between COPD caused by
      biomass and COPD caused by tobacco smoke, although these may be attributed in
      part to uneven gender distribution between the groups.

PMID- 24576450
TI  - The importance of the hydrophilic region of PsbL for the plastoquinone electron
      acceptor complex of Photosystem II.
AB  - The PsbL protein is a 4.5kDa subunit at the monomer-monomer interface of
      Photosystem II (PS II) consisting of a single membrane-spanning domain and a
      hydrophilic stretch of ~15 residues facing the cytosolic (or stromal) side of the
      photosystem. Deletion of conserved residues in the N-terminal region has been
      used to investigate the importance of this hydrophilic extension. Using
      Synechocystis sp. PCC 6803, three deletion strains: ?(N6-N8), ?(P11-V12) and
      ?(E13-N15), have been created. The ?(N6-N8) and ?(P11-V12) strains remained
      photoautotrophic but were more susceptible to photodamage than the wild type;
      however, the ?(E13-N15) cells had the most severe phenotype. The Delta(E13-N15)
      mutant showed decreased photoautotrophic growth, a reduced number of PS II
      centers, impaired oxygen evolution in the presence of PS II-specific electron
      acceptors, and was highly susceptible to photodamage. The decay kinetics of
      chlorophyll a variable fluorescence after a single turnover saturating flash and
      the sensitivity to low concentrations of PS II-directed herbicides in the
      Delta(E13-N15) strain indicate that the binding of plastoquinone to the QB
      binding site had been altered such that the affinity of QB is reduced. In
      addition, the PS II-specific electron acceptor 2,5-dimethyl-p-benzoquinone was
      found to inhibit electron transfer through the quinone-acceptor complex of the
      ?(E13-N15) strain. The PsbL Y20A mutant was also investigated and it exhibited
      increased susceptibility to photodamage and increased herbicide sensitivity. Our
      data suggest that the N-terminal hydrophilic region of PsbL influences forward
      electron transfer from QA through indirect interactions with the D-E loop of the
      D1 reaction center protein. Our results further indicate that disruption of
      interactions between the N-terminal region of PsbL and other PS II subunits or
      lipids destabilizes PS II dimer formation. This article is part of a special
      issue entitled: photosynthesis research for sustainability: keys to produce clean
      energy.

PMID- 24576451
TI  - Exploring the mechanism(s) of energy dissipation in the light harvesting complex
      of the photosynthetic algae Cyclotella meneghiniana.
AB  - Photosynthetic organisms have developed vital strategies which allow them to
      switch from a light-harvesting to an energy dissipative state at the level of the
      antenna system in order to survive the detrimental effects of excess light
      illumination. These mechanisms are particularly relevant in diatoms, which grow
      in highly fluctuating light environments and thus require fast and strong
      response to changing light conditions. We performed transient absorption
      spectroscopy on FCPa, the main light-harvesting antenna from the diatom
      Cyclotella meneghiniana, in the unquenched and quenched state. Our results show
      that in quenched FCPa two quenching channels are active and are characterized by
      differing rate constants and distinct spectroscopic signatures. One channel is
      associated with a faster quenching rate (16ns-1) and virtually no difference in
      spectral shape compared to the bulk unquenched chlorophylls, while a second
      channel is associated with a slower quenching rate (2.7ns-1) and exhibits an
      increased population of red-emitting states. We discuss the origin of the two
      processes in the context of the models proposed for the regulation of
      photosynthetic light-harvesting. This article is part of a special issue
      entitled: photosynthesis research for sustainability: keys to produce clean
      energy.

PMID- 24576452
TI  - Wildervanck's syndrome with severe inner ear dysplasia and agenesis of the right
      internal carotid artery.
AB  - We describe a case with Wildervanck syndrome (cervico-oculo-acoustic syndrome)
      comprising Klippel-Feil anomaly, retractio bulbi (Duane syndrome), and congenital
      sensorineural deafness. An 18-month male baby had a severe inner ear dysplasia,
      and MRI also showed a complex vascular carotid malformation associated. 

PMID- 24576453
TI  - Working memory in Farsi-speaking children with normal development and cochlear
      implant.
AB  - AIM AND BACKGROUND: Working memory has an important role in language acquisition
      and development of cognition skills. The ability of encoding, storage and
      retrieval of phonological codes, as activities of working memory, acquired by
      audition sense. Children with cochlear implant experience a period that they are
      not able to perceive sounds. In order to assess the effect of hearing on working
      memory, we investigated working memory as a cognition skill in children with
      normal development and cochlear implant. METHODS: Fifty students with normal
      hearing and 50 students with cochlear implant aged 5-7 years participated in this
      study. Children educated in the preschool, the first and second grades. Children
      with normal development were matched based on age, gender, and grade of education
      with cochlear implant. Two components of working memory including phonological
      loop and central executive were compared between two groups. Phonological loop
      assessed by nonword repetition task and forward digit span. To assess central
      executive component backward digit span was used. The developmental trend was
      studied in children with normal development and cochlear implant as well. The
      effect of age at implantation in children with cochlear implants on components of
      working memory was investigated. RESULTS: There are significant differences
      between children with normal development and cochlear implant in all tasks that
      assess working memory (p < 0.001). The children's age at implantation was
      negatively correlated with all tasks (p < 0.001). In contrast, duration of usage
      of cochlear implant set was positively correlated with all tasks (p < 0.001). The
      comparison of working memory between different grades showed significant
      differences both in children with normal development and in children with
      cochlear implant (p < 0.05). CONCLUSION: These results implied that children with
      cochlear implant may experience difficulties in working memory. Therefore, these
      children have problems in encoding, practicing, and repeating phonological units.
      The results also suggested working memory develops when the child grows up. In
      cochlear implant children, with decreasing age at implantation and increasing
      their experience in perceiving sound, working memory skills improved.

PMID- 24576454
TI  - Postoperative recurrent tracheoesophageal fistula: an unusual complication of
      oxidized regenerated cellulose (Surgicel(r)).
AB  - Oxidized regenerated cellulose (Surgicel((r))) is a commonly used material in
      Pediatric Surgery. We present a case of recurrent tracheoesophageal fistula
      (RTEF) repaired by Surgicel((r)). In this case, tracheoesophageal fistula (TEF)
      recurred due to migration of Surgicel into the tracheal and esophageal lumen. 

PMID- 24576455
TI  - Natural selection on human Y chromosomes.

PMID- 24576456
TI  - Protein interaction between p53 and Delta113p53 is required for the anti
      apoptotic function of Delta113p53.
AB  - Zebrafish Delta113p53, an N-terminal truncated p53 isoform, is a p53-target gene
      that antagonises p53-mediated apoptotic activity. Interestingly, Delta113p53 does
      not act on p53 in a dominant-negative manner, but rather interferes with the p53
      function by differentially modulating p53-target gene expression to protect cells
      from apoptosis. Previous studies showed that over-expressed Delta113p53 and p53
      proteins formed a complex. However, it is not known whether endogenous p53 and
      Delta113p53 proteins also interact with each other, and if this interaction is
      required for Delta113p53 to inhibit the apoptotic activity of full-length p53. In
      this study, we used two available zebrafish p53 antibodies to address these
      questions. One, Zfp53-N, only recognises full-length p53, whereas the other,
      Zfp53-A7C10, detects both full-length p53 and Delta113p53. Using Zfp53-N for
      immunoprecipitation and Zfp53-A7C10 for detection, we demonstrated that
      endogenous Delta113p53 and full-length p53 induced by a DNA-damaging drug formed
      a complex in vivo. Furthermore, of the six Delta113p53 mutants we generated with
      different point mutations in the oligomerisation domain, two failed to interact
      with p53 and lost the ability to modulate p53-target gene expression and inhibit
      p53-induced cell apoptosis. However, those Delta113p53 mutants that could
      interact with p53 retained the ability to antagonise the apoptotic activity of
      p53. Therefore, our data demonstrated that protein-protein interaction between
      Delta113p53 and p53 is essential for the anti-apoptotic function of Delta113p53.
      In addition, the two Delta113p53 mutants that failed to interact with p53 are
      also useful for the study of the mechanisms of other functions of Delta113p53.

PMID- 24576457
TI  - Targeted mutagenesis in Zea mays using TALENs and the CRISPR/Cas system.
AB  - Transcription activator-like effector nucleases (TALENs) and clustered regularly
      interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) systems
      have emerged as powerful tools for genome editing in a variety of species. Here,
      we report, for the first time, targeted mutagenesis in Zea mays using TALENs and
      the CRISPR/Cas system. We designed five TALENs targeting 4 genes, namely ZmPDS,
      ZmIPK1A, ZmIPK, ZmMRP4, and obtained targeting efficiencies of up to 23.1% in
      protoplasts, and about 13.3% to 39.1% of the transgenic plants were somatic
      mutations. Also, we constructed two gRNAs targeting the ZmIPK gene in maize
      protoplasts, at frequencies of 16.4% and 19.1%, respectively. In addition, the
      CRISPR/Cas system induced targeted mutations in Z. mays protoplasts with
      efficiencies (13.1%) similar to those obtained with TALENs (9.1%). Our results
      show that both TALENs and the CRISPR/Cas system can be used for genome
      modification in maize. 

PMID- 24576458
TI  - A long type of TBCK is a novel cytoplasmic and mitotic apparatus-associated
      protein likely suppressing cell proliferation.

PMID- 24576459
TI  - Acquired cardiomyopathy caused by cardiac Tsc1 deficiency.

PMID- 24576460
TI  - One novel long noncoding RNA lnc10 in Drosophila.

PMID- 24576461
TI  - Don't ask don't tell: Battered Women living in Sweden encounter with healthcare
      personnel and their experience of the care given.
AB  - In recent years there has been increased intimate partner violence (IPV) toward
      women. Research on the care provided to victims of IPV is limited. The purpose of
      the study was to gain a deeper understanding of women's lived experience of IPV
      and their encounters with healthcare professionals, social workers, and the
      police following IPV. A phenomenological hermeneutic method inspired by the
      philosophy of Paul Ricoeur was used. The method is based on text interpretation
      and gives voice to women's lived experience. Twelve women living at a women's
      shelter in Sweden narrated their IPV experiences. The study revealed that the
      women experienced retraumatization, uncaring behaviors, and unendurable suffering
      during their encounter with healthcare professionals. They were disappointed,
      dismayed, and saddened by the lack of support, care, and empathy. Nurses and
      other healthcare professionals must understand and detect signs of IPV as well as
      provide adequate care, as these women are vulnerable. IPV victims need to feel
      that they can trust healthcare professionals. Lack of trust can lead to less
      women reporting IPV and seeking help. 

PMID- 24576462
TI  - A medical student's reflection on palliative care: Managing emotional connection
      with patients.

PMID- 24576464
TI  - President's page: back to the future.

PMID- 24576463
TI  - Origin, duplication and reshuffling of plasmid genes: Insights from Burkholderia
      vietnamiensis G4 genome.
AB  - Using a computational pipeline based on similarity networks reconstruction we
      analysed the 1133 genes of the Burkholderia vietnamiensis (Bv) G4 five plasmids,
      showing that gene and operon duplication played an important role in shaping the
      plasmid architecture. Several single/multiple duplications occurring at intra-
      and/or interplasmids level involving 253 paralogous genes (stand-alone, clustered
      or operons) were detected. An extensive gene/operon exchange between plasmids and
      chromosomes was also disclosed. The larger the plasmid, the higher the number and
      size of paralogous fragments. Many paralogs encoded mobile genetic elements and
      duplicated very recently, suggesting that the rearrangement of the Bv plastic
      genome is ongoing. Concerning the "molecular habitat" and the "taxonomical
      status" (the Preferential Organismal Sharing) of Bv plasmid genes, most of them
      have been exchanged with other plasmids of bacteria belonging (or
      phylogenetically very close) to Burkholderia, suggesting that taxonomical
      proximity of bacterial strains is a crucial issue in plasmid-mediated gene
      exchange. 

PMID- 24576465
TI  - Comparative effects of TV watching, recreational computer use, and sedentary
      video game play on spontaneous energy intake in male children. A randomised
      crossover trial.
AB  - To compare the effects of three screen-based sedentary behaviours on acute energy
      intake (EI) in children. Normal-weight males aged 9-13 years participated in a
      randomised crossover trial conducted in a laboratory setting between November
      2012 and February 2013 in Auckland, New Zealand. EI during an ad libitum meal was
      compared for three 1-hour conditions: (1) television (TV) watching, (2) sedentary
      video game (VG) play, and (3) recreational computer use. The primary endpoint was
      total EI from food and drink. Mixed regression models were used to evaluate the
      treatment conditions adjusting for age, BMI, and appetite at baseline. A total of
      20 participants were randomised and all completed the three conditions. Total EI
      from food and drink in the TV, computer, and VG conditions was estimated at 820
      (SE 73.15), 685 (SE 73.33), and 696 (SE 73.16) kcal, respectively, with EI being
      significantly greater in the TV versus computer condition (+135; P = 0.04), a
      trend towards greater intake in the TV versus VG condition (+124; P = 0.06), but
      not significantly different between the computer and VG conditions (-10; P =
      0.87). TV watching was associated with greater EI compared with computer use, and
      a trend towards greater EI compared with VG play. 

PMID- 24576466
TI  - Completed egoism and intended altruism boost healthy food choices.
AB  - Based on the self-licensing literature and goal theory, we expected and found
      that completed (im)moral actions lead to markedly different food choices (Studies
      1 & 2) than intended (im)moral actions (Study 2). In Study 1, people more often
      chose healthy over unhealthy food options when they recalled a completed egoistic
      action than when they recalled a completed altruistic action. Study 2 confirmed
      this finding and furthermore showed that the self-licensing effect in food
      choices is moderated by the action stage (completed versus intended) of the moral
      or immoral action. This article extends the existing self-licensing literature
      and opens up new perspectives for changing consumers' food consumption behavior. 

PMID- 24576468
TI  - The polio eradication end game: what it means for Europe.

PMID- 24576467
TI  - Diagnostic metagenomics: potential applications to bacterial, viral and parasitic
      infections.
AB  - The term 'shotgun metagenomics' is applied to the direct sequencing of DNA
      extracted from a sample without culture or target-specific amplification or
      capture. In diagnostic metagenomics, this approach is applied to clinical samples
      in the hope of detecting and characterizing pathogens. Here, I provide a
      conceptual overview, before reviewing several recent promising proof-of-principle
      applications of metagenomics in virus discovery, analysis of outbreaks and
      detection of pathogens in contemporary and historical samples. I also evaluate
      future prospects for diagnostic metagenomics in the light of relentless
      improvements in sequencing technologies.

PMID- 24576469
TI  - Note from the editors: polio - good news and bad news.

PMID- 24576470
TI  - Development and validation of a real time quantitative reverse transcription
      polymerase chain reaction (qRT-PCR) assay for investigation of wild poliovirus
      type 1-South Asian (SOAS) strain reintroduced into Israel, 2013 to 2014.
AB  - In February 2013, wild poliovirus type 1 (WPV1) was reintroduced into southern
      Israel and resulted in continuous silent circulation in the highly immune
      population. As a part of the public health emergency response, a novel real time
      quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assay was
      developed, to allow for the sensitive and specific detection of the
      circulatingWPV1-South Asian (SOAS) strain. Specific primers and probes derived
      from the VP-1 region were designed, based on sequenced sewage isolates, and used
      to simultaneously amplify this WPV1-SOAS sequence together with bacteriophage MS
      2 as internal control. High titre WPV1-SOAS stock virus was used for assay
      optimisation and 50 processed sewage samples collected from southern Israel and
      tested by reference culture based methods were used for analytical validation of
      the assay's performance. The limit of detection of the multiplex qRT-PCR (SOAS/MS
      2) assay was 0.1 plaque-forming unit (pfu)/reaction (20 pfu/mL) for WPV1-SOAS RNA
      with 100% sensitivity, specificity, positive and negative predictive values when
      compared to the culture based method. The turnaround time was rapid, providing
      results for environmental samples within 24 to 48 hours from completion of sewage
      processing, instead of five to seven days by culture-based analysis. Direct
      sewage testing by qRT-PCR assay proved to be a useful tool for rapid detection
      and environmental surveillance of WPV1-SOAS circulating strain during emergency
      response. Application of the approach for detection of WPV1-SOAS in stool samples
      obtained during acute flaccid paralysis (AFP) surveillance or field surveys
      should be further evaluated.

PMID- 24576471
TI  - Molecular epidemiology of silent introduction and sustained transmission of wild
      poliovirus type 1, Israel, 2013.
AB  - Poliovirus vaccine coverage in Israel is over 90%. The last nine birth cohorts
      have been vaccinated exclusively with inactivated polio vaccine (IPV). However,
      between February and July 2013 type 1 wild poliovirus (WPV1) was detected
      persistently in 10 and intermittently in 8 of 47 environmental surveillance sites
      in southern and central Israel and in 30 stool samples collected during July from
      healthy individuals in southern Israel. We report results of sequence and
      phylogenetic analyses of genes encoding capsid proteins to determine the source
      and transmission mode of the virus. WPV1 capsid protein 1 nucleotide sequences
      were most closely related to South Asia (SOAS) cluster R3A polioviruses
      circulating in Pakistan in 2012 and isolated from Egyptian sewage in December
      2012. There was no noticeable geographical clustering within WPV1-positive sites.
      Uniform codon usage among isolates from Pakistan, Egypt and Israel showed no
      signs of optimisation or deoptimisation. Bayesian phylogenetic time clock
      analysis of the entire capsid coding region (2,643 nt) with a 1.1% evolutionary
      rate indicated that Israeli and Egyptian WPV1-SOAS lineages diverged in September
      2012, while Israeli isolates split into two sub-branches after January 2013. This
      suggests one or more introduction events into Israel with subsequent silent
      circulation despite high population immunity.

PMID- 24576472
TI  - Immunity against poliomyelitis in the Netherlands, assessed in 2006 to 2007: the
      importance of completing a vaccination series.
AB  - Europe has been declared polio-free since 2002. Here we describe the
      seroprotection against poliomyelitis in the Dutch population using banked serum
      samples. Samples from 1,581 inhabitants of eight municipalities with low
      vaccination coverage (LVC) and an additional 6,386 samples from a nationwide (NS)
      group (clinical trial number: ISRCTN20164309; collected in 2006-07) were tested
      for neutralising antibodies (log2 reciprocal titres (GMT); non-protection <3)
      against all three poliomyelitis serotypes. Demographic and epidemiological data
      were used for statistical regression analysis. Seroprevalence in the NS was 94.6%
      (type 1), 91.8% (type 2) and 84.0% (type 3). Infants (0-7 months-old) had >=80%
      seroprevalence for all serotypes. The highest seroprevalence was found in
      children, with type 1 and type 2 in five year-olds and type 3 in nine to 10 year
      olds. In the LVC group, orthodox protestants, many of whom refuse vaccination,
      showed seroprevalence rates of 64.9% (type 1), 61.0% (type 2) and 62.1% (type 3).
      In the NS group, non-Western immigrants and travellers to non-European continents
      had higher seroprevalences compared to Western immigrants and travellers within
      Europe, respectively. The Dutch National Immunisation Programme against
      poliomyelitis has provided good seroprotection, with high and long-lasting GMTs
      against all serotypes upon completion. The unvaccinated population remains at
      risk.

PMID- 24576473
TI  - Intensified environmental surveillance supporting the response to wild poliovirus
      type 1 silent circulation in Israel, 2013.
AB  - An emergency response was triggered by recovery of wild poliovirus type 1 (WPV1)
      of the South Asia (SOAS) lineage from sewage in southern Israel in April 2013
      during routine environmental surveillance. Public health risk assessment
      necessitated intensification of environmental surveillance in order to facilitate
      countrywide monitoring of WPV1-SOAS circulation. This involved increasing
      sampling frequency and broadening the geographical area, for better coverage of
      the population at risk, as well as modifying sewage testing algorithms to
      accommodate a newly developed WPV1-SOAS-specific quantitative real-time RT-PCR
      assay for screening of RNA extracted directly from sewage concentrates, in
      addition to standard virus isolation. Intensified surveillance in 74 sites across
      Israel between 1 February and 31 August 2013 documented a sustained high viral
      load of WPV1-SOAS in sewage samples from six Bedouin settlements and two cities
      with Jewish and Arab populations in the South district. Lower viral loads and
      intermittent detection were documented in sampling sites representing 14 mixed
      communities in three of the five health districts in central and northern Israel.
      Environmental surveillance plays a fundamental role in routine monitoring of WPV
      circulation in polio-free countries. The rapid assay specific for the circulating
      strain facilitated implementation of intensified surveillance and informed the
      public health response and decision-making.

PMID- 24576474
TI  - The 2010 outbreak of poliomyelitis in Tajikistan: epidemiology and lessons
      learnt.
AB  - A large outbreak of poliomyelitis, with 463 laboratory-confirmed and 47 polio
      compatible cases, took place in 2010 in Tajikistan. Phylogenetic analysis of the
      viral VP1 gene suggested a single importation of wild poliovirus type 1 from
      India in late 2009, its further circulation in Tajikistan and expansion into
      neighbouring countries, namely Kazakhstan, Russia, Turkmenistan and Uzbekistan.
      Whole-genome sequencing of 14 isolates revealed recombination events with
      enterovirus C with cross-overs within the P2 region. Viruses with one class of
      recombinant genomes co-circulated with the parental virus, and representatives of
      both caused paralytic poliomyelitis. Serological analysis of 327 sera from acute
      flaccid paralysis cases as well as from patients with other diagnoses and from
      healthy people demonstrated inadequate immunity against polio in the years
      preceding the outbreak. Evidence was obtained suggesting that vaccination against
      poliomyelitis, in rare cases, may not prevent the disease. Factors contributing
      to the peculiarities of this outbreak are discussed. The outbreak emphasises the
      necessity of continued vaccination against polio and the need, at least in risk
      areas, of quality control of this vaccination through well planned serological
      surveillance.

PMID- 24576475
TI  - Silent reintroduction of wild-type poliovirus to Israel, 2013 - risk
      communication challenges in an argumentative atmosphere.
AB  - Israel has been certified as polio-free by the World Health Organization and its
      routine immunisation schedule consists of inactivated poliovirus vaccine (IPV)
      only. At the end of May 2013, the Israeli Ministry of Health (MOH) has confirmed
      the reintroduction of wild-type poliovirus 1 into the country. Documented ongoing
      human-to-human transmission necessitated a thorough risk assessment followed by a
      supplemental immunisation campaign using oral polio vaccine (OPV). The unusual
      situation in which ongoing poliovirus transmission was picked up through an early
      warning system of sewage monitoring without active polio cases, brought about
      significant challenges in risk communication. This paper reviews the challenges
      faced by the MOH and the communication strategy devised, in order to facilitate
      and optimise the various components of the public health response, particularly
      vaccination. Lessons learned from our recent experience may inform risk
      communication approaches in other countries that may face a similar situation as
      global polio eradication moves towards the 'End game'.

PMID- 24576478
TI  - Involvement of cholesterol in hepatitis B virus X protein-induced abnormal lipid
      metabolism of hepatoma cells via up-regulating miR-205-targeted ACSL4.
AB  - Hepatitis B virus X protein (HBx) plays crucial roles in the development of
      hepatocellular carcinoma (HCC). The abnormal lipid metabolism is involved in the
      hepatocarcinogenesis. We previously reported that HBx suppressed miR-205 in
      hepatoma cells. In this study, we supposed that HBx-decreased miR-205 might
      contribute to the abnormal lipid metabolism according to the bioinformatics
      analysis. Interestingly, we showed that the expression levels of acyl-CoA
      synthetase long-chain family member 4 (ACSL4) were negatively associated with
      those of miR-205 in clinical HCC tissues. Then, we validated that miR-205 was
      able to inhibit the expression of ACSL4 at the levels of mRNA and protein through
      targeting its 3'UTR. Strikingly, we found that HBx was able to increase the
      levels of cellular cholesterol, a metabolite of ACSL4, in hepatoma cells, which
      could be blocked by miR-205 (or Triacsin C, an inhibitor of ACSL4). However, anti
      miR-205 could increase the levels of cholesterol in the cells. Moreover, we
      demonstrated that the levels of cholesterol were increased in the liver of HBx
      transgenic mice in a time course manner. Functionally, oil red O staining
      revealed that HBx promoted lipogenesis in HepG2 cells, which could be abolished
      by miR-205 (or Triacsin C). However, anti-miR-205 was able to accelerate
      lipogenesis in the cells. Interestingly, the treatment with Triacsin C could
      remarkably block the role of anti-miR-205 in the event. Thus, we conclude that
      miR-205 is able to target ACSL4 mRNA. The HBx-depressed miR-205 is responsible
      for the abnormal lipid metabolism through accumulating cholesterol in hepatoma
      cells. 

PMID- 24576479
TI  - Active bleeding caused by portal hypertensive gastropathy.

PMID- 24576480
TI  - Effects of olive and fish oil Ca soaps in ewe diets on milk fat and muscle and
      subcutaneous tissue fatty-acid profiles of suckling lambs.
AB  - Enhancing healthy fatty acids (FAs) in ewe milk fat and suckling lamb tissues is
      an important objective in terms of improving the nutritional value of these foods
      for the consumer. The present study examined the effects of feeding-protected
      lipid supplements rich in unsaturated FAs on the lipid composition of ewe milk,
      and subsequently in the muscle and subcutaneous adipose tissues of lambs suckling
      such milk. Thirty-six pregnant Churra ewes with their new-born lambs were
      assigned to one of three experimental diets (forage/concentrate ratio 50 : 50),
      each supplemented with either 3% Ca soap FAs of palm (Control), olive (OLI) or
      fish (FO) oil. The lambs were nourished exclusively by suckling for the whole
      experimental period. When the lambs reached 11 kg BW, they were slaughtered and
      samples were taken from the Longissimus dorsi and subcutaneous fat depots.
      Although milk production was not affected by lipid supplementation, the FO diet
      decreased fat content (P0.05) and other trans-FAs between Control and FO
      treatments would indicate that FO treatment does not alter rumen biohydrogenation
      pathways under the assayed conditions. Changes in dam milk FA composition induced
      differences in the FA profiles of meat and fat depots of lambs, preferentially
      incorporated polyunsaturated FAs into the muscle rather than storing them in the
      adipose tissue. In the intramuscular fat of the FO treatment, all the n-3 FAs
      reached their highest concentrations: 0.97 (18:3 n-3), 2.72 (20:5 n-3), 2.21
      (22:5 n-3) and 1.53% (22:6 n-3). In addition, not only did FO intramuscular fat
      have the most cis-9, trans-11 18:2 (1.66%) and trans-11 18:1 (3.75%), but also
      the lowest n-6/n-3 ratio (1.80) and saturated FA content were not affected.
      Therefore, FO exhibited the best FA profile from a nutritional point of view. 

PMID- 24576477
TI  - Effects on specific promoter DNA methylation in zebrafish embryos and larvae
      following benzo[a]pyrene exposure.
AB  - Benzo[a]pyrene (BaP) is an established carcinogen and reproductive and
      developmental toxicant. BaP exposure in humans and animals has been linked to
      infertility and multigenerational health consequences. DNA methylation is the
      most studied epigenetic mechanism that regulates gene expression, and mapping of
      methylation patterns has become an important tool for understanding pathologic
      gene expression events. The goal of this study was to investigate aberrant
      changes in promoter DNA methylation in zebrafish embryos and larvae following a
      parental and continued embryonic waterborne BaP exposure. A total of 21 genes
      known for their role in human diseases were selected to measure percent
      methylation by multiplex deep sequencing. At 96hpf (hours post fertilization)
      compared to 3.3hpf, dazl, nqo1, sox3, cyp1b1, and gstp1 had higher methylation
      percentages while c-fos and cdkn1a had decreased CG methylation. BaP exposure
      significantly reduced egg production and offspring survival. Moreover, BaP
      decreased global methylation and altered CG, CHH, and CHG methylation both at 3.3
      and 96hpf. CG methylation changed by 10% or more due to BaP in six genes (c-fos,
      cdkn1a, dazl, nqo1, nrf2, and sox3) at 3.3hpf and in ten genes (c-fos, cyp1b1,
      dazl, gstp1, mlh1, nqo1, pten, p53, sox2, and sox3) at 96hpf. BaP also induced
      gene expression of cyp1b1 and gstp1 at 96hpf which were found to be
      hypermethylated. Further studies are needed to link aberrant CG, CHH, and CHG
      methylation to heritable epigenetic consequences associated with disease in later
      life.

PMID- 24576481
TI  - Ethyl pyruvate ameliorates 3-nitropropionic acid-induced striatal toxicity
      through anti-neuronal cell death and anti-inflammatory mechanisms.
AB  - The potential neuroprotective value of ethyl pyruvate (EP) for the treatment of
      the striatal toxicity is largely unknown. We investigated whether EP promotes the
      survival of striatal neurons in a 3-nitropropionic acid (3-NP)-induced mouse
      model of Huntington's disease (HD). EP (5, 10, 20, and 40mg/kg/day, i.p.) was
      daily injected from 30min before 3-NP intoxication (pretreatment) and from
      onset/progression/peak point of neurological impairment by 3-NP intoxication. EP
      produced a neuroprotective effect in dose- and time-dependant manners. EP
      pretreatment of 40mg/kg/day produced the best neuroprotective effect among other
      conditions. Pretreatment of EP significantly attenuated neurological impairment
      and lethality and prevented formation of lesion area and neuronal loss in the
      striatum after 3-NP intoxication. This neuroprotection afforded by EP was
      associated with the suppression of succinate dehydrogenase activity, apoptosis,
      and microglial activation. The suppressive effect of EP corresponded to the down
      regulation of mitogen-activated protein kinases (MAPKs) and nuclear factor-kappa
      B (NF-kappaB) signal pathways, and mRNA expression of inflammatory mediators
      including tumor necrosis factor-alpha, interleukin (IL)-1beta, IL-6, inducible
      nitric oxide synthase, and cyclooxygenase-2 in the striatum after 3-NP
      intoxication. Interestingly, the intrathecal introduction of inhibitors MAPKs and
      NF-kappaB into control mice decreased the lethality after 3-NP intoxication. Our
      findings indicate that EP may effectively alleviate 3-NP-induced striatal
      toxicity by inhibition of the MAPKs and NF-kappaB pathways in the striatum, and
      that EP has a wide therapeutic window, suggesting that EP may have therapeutic
      value in the treatment of aspects of HD's disease related to inflammation. 

PMID- 24576484
TI  - Is nerve-sparing surgery suitable for deeply infiltrating endometriosis?
AB  - OBJECTIVE: To investigate the efficacy of nerve-sparing surgery for deeply
      infiltrating endometriosis (DIE) and the bladder and sexual dysfunction that
      follow this procedure. STUDY DESIGN: A total of 108 women with DIE underwent
      conventional surgery (group A, n=63) and nerve-sparing surgery (group B, n=45).
      Three validated interview-based questionnaires - the visual analogue scale (VAS),
      the international prostate score symptom (IPSS), and the female sexual function
      index (FSFI) - were used to evaluate the efficacy and associated complications.
      RESULTS: The VAS scores significantly decreased in both groups A and B after
      surgery, although two patients (4.4%) in group B had no improvement in their pain
      symptoms. The total FSFI and each domain scores significantly increased in the
      two groups after surgery except for satisfaction at the 24-month follow up in
      group A. Nine patients (15.9%) in group A required self-catheterization
      postoperatively. Based on the IPSS scores, a significant alteration in voiding
      symptoms in group A was observed at 6 months but not at 12 months or 24 months
      after surgery. In group B, however, no significant difference or self
      catheterization requirement was observed after surgery. CONCLUSIONS: Reduced
      bladder and sexual dysfunction, but with a risk of absence of pain relief,
      suggests that the pros and cons of nerve-sparing surgery for DIE should carefully
      be evaluated before operation.

PMID- 24576483
TI  - Irisin: a potentially candidate marker for myocardial infarction.
AB  - Myocardial infarction (MI) causes energy depletion through imbalance between
      coronary blood supply and myocardial demand. Irisin produced by the heart reduces
      ATP production by increasing heat generation. Energy depletion affects irisin
      concentration in circulation and cardiac tissues, suggesting an association with
      MI. We examined: (1) irisin expression immunohistochemically in rat heart,
      skeletal muscle, kidney and liver in isoproterenol (ISO)-induced MI, and (2)
      serum irisin concentration by ELISA. Rats were randomly allocated into 6 groups
      (n=6), (i) control, (ii) ISO (1h), (iii) ISO (2h), (iv) ISO (4h), (v) ISO (6h),
      and (vi) ISO (24h), 200mg ISO in each case. Rats were decapitated and the blood
      and tissues collected for irisin analysis. Blood was centrifuged at 1792 g for 5
      min. Tissues were washed with saline and fixed in 10% formalin for histology.
      Serum irisin levels gradually decreased from 1h to 24h in MI rats compared with
      controls, the minimum being at 2h, increasing again after 6h. Cardiac muscle
      cells, glomerular, peritubular renal cortical interstitial cells, hepatocytes and
      liver sinusoidal cells and perimysium, endomysium and nucleoi of skeletal muscle
      were irisin positive, but its synthesis decreased 1-4h after MI. At all time
      points, irisin increased near myocardial connective tissue, with production in
      skeletal muscle, liver and kidney recovering after 6h, although slower than
      controls. Unique insight into the pathogenesis of MI is shown, and the gradually
      decrease of serum irisin might be a diagnostic marker for MI.

PMID- 24576482
TI  - Leukocyte infiltration into spinal cord of EAE mice is attenuated by removal of
      endothelial leptin signaling.
AB  - Leptin, a pleiotropic adipokine, crosses the blood-brain barrier (BBB) and blood
      spinal cord barrier (BSCB) from the periphery and facilitates experimental
      autoimmune encephalomyelitis (EAE). EAE induces dynamic changes of leptin
      receptors in enriched brain and spinal cord microvessels, leading to further
      questions about the potential roles of endothelial leptin signaling in EAE
      progression. In endothelial leptin receptor specific knockout (ELKO) mice, there
      were lower EAE behavioral scores in the early phase of the disorder, better
      preserved BSCB function shown by reduced uptake of sodium fluorescein and
      leukocyte infiltration into the spinal cord. Flow cytometry showed that the ELKO
      mutation decreased the number of CD3 and CD45 cells in the spinal cord, although
      immune cell profiles in peripheral organs were unchanged. Not only were CD4(+)
      and CD8(+) T lymphocytes reduced, there were also lower numbers of CD11b(+)Gr1(+)
      granulocytes in the spinal cord of ELKO mice. In enriched microvessels from the
      spinal cord of the ELKO mice, the decreased expression of mRNAs for a few tight
      junction proteins was less pronounced in ELKO than WT mice, as was the elevation
      of mRNA for CCL5, CXCL9, IFN-gamma, and TNF-alpha. Altogether, ELKO mice show
      reduced inflammation at the level of the BSCB, less leukocyte infiltration, and
      better preserved tight junction protein expression and BBB function than WT mice
      after EAE. Although leptin concentrations were high in ELKO mice and
      microvascular leptin receptors show an initial elevation before inhibition during
      the course of EAE, removal of leptin signaling helped to reduce disease burden.
      We conclude that endothelial leptin signaling exacerbates BBB dysfunction to
      worsen EAE. 

PMID- 24576485
TI  - Women with clomiphene citrate resistant polycystic ovarian disease: predictors of
      spontaneous ovulation after laparoscopic ovarian drilling.
AB  - OBJECTIVE: To evaluate the role of different clinical, biochemical and
      sonographic factors as predictors of spontaneous ovulation after laparoscopic
      ovarian drilling (LOD) in women with clomiphene citrate resistant polycystic
      ovarian disease (CCR-PCOD). STUDY DESIGN: This prospective study recruited 251
      infertile women with CCR-PCOD. Several clinical, biochemical and sonographic
      criteria were tested as possible predictors of spontaneous ovulation after LOD
      using multivariate analysis. RESULTS: Women with higher preoperative levels of
      LH, FSH and/or androstenedione had significantly higher rates of spontaneous
      ovulation within the first eight weeks after LOD, but only FSH and
      androstenedione were found to be independent predictors. Other factors including
      age, BMI, type of infertility, duration of infertility, menstrual pattern,
      testosterone level, ovarian volume and SHBG were insignificant predictors.
      Receiver-operating characteristic (ROC) curves derived from FSH, LH,
      androstenedione, and a logistic regression model showed that the best cut-off
      values were 4.1IU/l, 7.8IU/l, 1.2ng/ml, and 0.4897, respectively, with
      sensitivity of 91.18%, 100%, 73.53%, and 88.24% and specificity of 69.57%,
      69.57%, 65.22%, and 73.91% for FSH, LH, androstenedione, and logistic regression
      model respectively. An extended follow up (9 months after LOD) was conducted for
      the anovulatory and the non-pregnant ovulatory women, who were treated
      individually according to their clinical situation. Of these women, 53.5%
      (69/129) got pregnant, resulting in a cumulative pregnancy rate of 48% (82/171).
      Of these pregnancies, 16/82 (19.5%) were spontaneous while 35.4% (29/82) and
      45.1% (37/82) occurred after ovulation induction by CC and gonadotropins,
      respectively. CONCLUSION: This study supports the use of androstenedione, LH and
      FSH as a simple reliable tool in triaging patients with CCR-PCOD to select the
      ideal candidates for LOD.

PMID- 24576486
TI  - Summer increase of Legionnaires' disease 2010 in The Netherlands associated with
      weather conditions and implications for source finding.
AB  - During August and September 2010 an unexpected high number of domestic cases of
      Legionnaires' disease (LD) were reported in The Netherlands. To examine this
      increase, patient characteristics and results of source finding and environmental
      sampling during the summer peak were compared to other domestic cases in 2008
      2011. This analysis did not provide an explanation for the rise in cases. A
      similar increase in LD cases in 2006 was shown to be associated with warm and wet
      weather conditions, using an extended Poisson regression model with adjustment
      for long-term trends. This model was optimized with the new data from 2008 to
      2011. The increase in 2010 was very accurately described by a model, which
      included temperature in the preceding 4 weeks, and precipitation in the preceding
      2 weeks. These results confirm the strong association of LD incidence with
      weather conditions, but it remains unclear which environmental sources
      contributed to the 2010 summer increase.

PMID- 24576487
TI  - Genetic elimination of Nrf2 aggravates secondary complications except for
      vasospasm after experimental subarachnoid hemorrhage in mice.
AB  - Nuclear factor erythroid 2-related factor 2 (Nrf2) is a key endogenous protective
      regulator in the body. This study aimed to explore the role of Nrf2 in
      subarachnoid hemorrhage (SAH)-induced secondary complications. Wild type (WT) and
      Nrf2 knockout (KO) mice were subjected to experimental SAH by injecting fresh
      autologous blood into pre-chiasmatic cistern. The absence of Nrf2 function in
      mice resulted in exacerbated brain injury with increased brain edema, blood-brain
      barrier (BBB) disruption, neural apoptosis, and severe neurological deficits at
      24h after SAH. Moreover, cerebral vasospasm was severe at 24h after SAH, but not
      significantly different between WT and Nrf2 KO mice after SAH. Meanwhile,
      Molondialdehyde (MDA) was increased and GSH/GSSG ratio was decreased in Nrf2 KO
      mice after SAH. Furthermore, higher expression of TNF-alpha and IL-1beta was also
      found after SAH in Nrf2 KO mice. In conclusion, our results revealed that Nrf2
      plays an important role in attenuating SAH-induced secondary complications by
      regulating excessive oxidative stress and inflammatory response. 

PMID- 24576488
TI  - Inhibition of inducible nitric oxide synthase and interleukin-1beta expression by
      tunicamycin in cultured glial cells exposed to lipopolysaccharide.
AB  - Endoplasmic reticulum (ER) stress has recently been implicated in human diseases
      such as Alzheimer's disease (AD) and Parkinson's disease (PD). However, the link
      between the immune system, ER stress, and the development of neurodegenerative
      diseases has not yet been clarified in detail. Mouse primary cultured astrocytes
      were treated with lipopolysaccharide (LPS) and/or tunicamycin (Tm), and inducible
      nitric oxide synthase (iNOS) and interleukin (IL)-1beta levels were then measured
      using RT-PCR, ELISA, and Western blotting. Activation of the immune system by LPS
      triggered inflammatory responses in astrocytes, as measured by the induction of
      iNOS and IL-1beta. Tm-induced ER stress inhibited the LPS-induced expression of
      IL-1beta and iNOS at the protein level. On the other hand, ER stress alone did
      not induce the expression of IL-1beta or iNOS. The inhibitory effect of ER stress
      on iNOS and IL-1beta may not be mediated transcriptionally as we did not observe
      inhibition at the mRNA level. LPS-induced iNOS protein levels were attenuated by
      the Tm post-treatment in the absence of LPS. Overall, these results suggest that
      ER stress negatively regulates the expression of IL-1beta and iNOS in LPS
      activated astrocytes. 

PMID- 24576489
TI  - Endosomal localization of FIP3/Arfophilin-1 and its involvement in dendritic
      formation of mouse hippocampal neurons.
AB  - Endosomal trafficking mediated by Rab11 and Arf6 small GTPases is essential for
      various neuronal functions. Family of Rab11-interacting protein 3
      (FIP3)/Arfophilin-1, also termed Eferin, is a dual effector for Rab11 and Arf6
      and implicated in endosomal trafficking during cytokinesis. To understand the
      neuronal functions of FIP3, we first showed the widespread neuronal expression of
      FIP3 mRNA in adult mouse brain by in situ hybridization. Immunohistochemical
      analysis showed the association of FIP3 with a subpopulation of endosomes labeled
      with EEA1 and syntaxin 12 in hippocampal neurons. Immunoblot analysis showed the
      progressive increase of FIP3 with a peak around postnatal day 15 during
      hippocampal development. Furthermore, knockdown of endogenous FIP3 decreased the
      total dendritic length of cultured hippocampal neurons with a concomitant
      increase in the number of short (<40MUm) primary dendrites. Together, FIP3 is
      suggested to regulate dendritic formation possibly through Rab11- and Arf6
      mediated endosomal trafficking. 

PMID- 24576490
TI  - Amyloid beta peptide (25-35) in picomolar concentrations modulates the function
      of glycine receptors in rat hippocampal pyramidal neurons through interaction
      with extracellular site(s).
AB  - beta-Amyloid peptide (Abeta) plays a central role in the pathogenesis of
      Alzheimer's disease, but in lower amounts it is found in normal brains where it
      participates in physiological processes and probably regulates synaptic
      plasticity. This study investigated the effects of physiologically relevant
      concentrations of Abeta (1 pM-100 nM), fragment 25-35, on glycine-mediated
      membrane current in acutely isolated rat hippocampal pyramidal neurons using
      whole-cell patch-clamp technique. We have found that short (600 ms) co
      application of glycine with Abeta caused reversible dose-dependent and voltage
      independent acceleration of desensitization of glycine current. The peak
      amplitude of the current remained unchanged. The effect of picomolar Abeta
      concentrations persisted in the presence of 1 uM Abeta in the pipette solution,
      implying that Abeta bounds to extracellular site(s). Concentration-dependence
      curve was N-shaped with maximums at 100 pM and 100 nM, suggesting the existence
      of two binding sites, which may interact with each other. Glycine current
      resistant to 100 uM picrotoxin, was insensitive to Abeta, which suggests that
      Abeta affected mainly homomeric glycine receptors. When Abeta was added to bath
      solution, besides acceleration of desensitization, it caused reversible dose
      dependent reduction of glycine current peak amplitude. These results demonstrate
      that physiological (picomolar) concentrations of Abeta reversibly augment the
      desensitization of glycine current, probably by binding to external sites on
      homomeric glycine receptors. Furthermore, Abeta can suppress the peak amplitude
      of glycine current, but this effect develops slowly and may be mediated through
      some intracellular machinery.

PMID- 24576491
TI  - Effects of lead-spiked sediments on freshwater bivalve, Hyridella australis:
      linking organism metal exposure-dose-response.
AB  - Lead entering aquatic ecosystems adsorbs to sediments and has the potential to
      cause adverse effects on the health of benthic organisms. To evaluate the
      freshwater bivalve Hyridella australis as a bioindicator for sediment toxicity,
      their exposure-dose and response to lead contaminated sediments (< 0.01, 205 +/-
      9 and 419 +/- 16 MUg/g dry mass) was investigated in laboratory microcosms using
      28 day exposures. Despite high concentrations of lead in the sediments, organisms
      accumulated low concentrations of lead in their tissues after 28 days of exposure
      (low treatment: 2.2 +/- 0.2 MUg/g dry mass, high treatment: 4.2 +/- 0.1 MUg/g dry
      mass), however, accumulated lead concentrations in lead exposed organisms were
      two fold (low treatment) and four fold (high treatment) higher than that of
      unexposed organisms (1.2 +/- 0.3 MUg/g dry mass). Accumulation of lead by H.
      australis may have occurred as analogues of calcium and magnesium. Labial palps
      accumulated significantly more lead than other tissues. Of the lead accumulated
      in the hepatopancreas, 83%-91% was detoxified and stored in metal rich granules.
      The proportions and concentrations of lead in this fraction increased with lead
      exposure, which suggests that lead detoxification pathway plays an important role
      in metal tolerance of H. australis. The biologically active lead was mainly
      present in the mitochondrial fraction which increased with lead exposure. Total
      antioxidant capacity of H. australis significantly decreased while lipid
      peroxidation and lysosomal membrane destabilation increased with lead exposure.
      This study showed a clear lead exposure-dose-response relationship and indicates
      that H. australis would be a good biomonitor for lead in freshwater ecosystems.

PMID- 24576492
TI  - Di-n-butyl phthalate causes estrogenic effects in adult male Murray rainbowfish
      (Melanotaenia fluviatilis).
AB  - Phthalic acid esters (PAEs) are a class of synthetic industrial chemicals
      commonly found in the aquatic environment worldwide. PAEs have been recognised as
      anti-androgens in male mammals but little is known about their endocrine
      disrupting effects in fish. This study investigated the effects of 7-day
      exposures to nominal (measured) concentrations of 125 (62), 250 (140), 500 (230)
      and 1,000 (383) MUg/L of di-n-butyl phthalate (DnBP) on the biomarkers of
      reproduction in adult male Murray River rainbowfish (Melanotaenia fluviatilis)
      using molecular, biochemical and histological endpoints. None of the tested
      concentrations of DnBP had any effect on survival or the vital body indices of
      the fish. The sizes of spermatogonia, Type A and B spermatocytes and spermatids
      were significantly smaller relative to the controls after treatment with DnBP.
      This was accompanied by a significant increase in the proportion of spermatogonia
      in fish treated with 250-1,000 MUg/L of DnBP in comparison to the unexposed fish.
      At the end of the exposure period, the expressions of the transcripts for the
      androgen receptors alpha and beta were significantly elevated in the livers of
      the fish treated with 500 and 1,000 MUg/L of DnBP. In addition, there was also an
      increase in the circulating concentrations of vitellogenin in the plasma in the
      higher treatment groups. An induction in the activity of aromatase was noted in
      the brains of 1,000 MUg/L DnBP-treated fish. This was accompanied by an increase
      in the hepatic expression of the genes (here and later, whenever the phrase gene
      expression is used as a synonym for gene transcription although it is
      acknowledged that it is also regulated, e.g., by translation, mRNA stability and
      protein stability) encoding for the oestrogen receptors alpha and beta and
      choriogenin L. Collectively, an increase in the proportion of spermatogonia in
      the testes, the upregulation of the genes for the oestrogen receptors and
      choriogenin in the liver, an induction in the brain aromatase activity and the
      increase in the circulating levels of plasma vitellogenin suggest that continuous
      exposures for 7 days to sub-acute concentrations of DnBP can adversely affect the
      reproductive health of the male Murray rainbowfish by an estrogenic mode of
      action.

PMID- 24576493
TI  - Effect of diet-induced obesity on BK(Ca) function in contraction and dilation of
      rat isolated middle cerebral artery.
AB  - This study examined the effect of diet-induced obesity on the functional role of
      large-conductance Ca2+-activated K+ channels (BK(Ca)) in rat middle cerebral
      arteries. Male Sprague-Dawley rats were fed a control (chow) or high-fat diet for
      16-20 weeks. Diet-induced obesity decreased maximum bradykinin-induced dilation
      of isolated, pressurized (80 mmHg) arteries, but vasodilation induced by sodium
      nitroprusside (SNP) was unaltered. Responses to bradykinin and SNP in arteries
      from both control and obese rats were abolished by combination of the nitric
      oxide synthase (NOS) and guanylate cyclase (sGC) inhibitors L-NAME (100 MUmol/L)
      and ODQ (10 MUmol/L) respectively, or by the BK(Ca) blocker iberiotoxin (IBTX,
      0.1 MUmol/L). Vasodilation induced by the PAR2 agonist SLIGRL in arteries from
      control-diet rats was abolished by L-NAME/ODQ, but unaffected by IBTX. Obesity
      greatly reduced the inhibitory effect of L-NAME/ODQ on SLIGRL-induced dilation,
      whereas IBTX alone now inhibited responses to SLIGRL. Neither obesity nor IBTX
      altered the responsiveness of the arteries to vasoconstrictors 5
      hydroxytryptamine (5-HT) or angiotensin II (Ang II). Obesity had variable effects
      on the functional role of BK(Ca) in the middle-cerebral artery depending upon the
      agent used to stimulate the channel, reflecting the variety of mechanisms by
      which BK(Ca) may be activated.

PMID- 24576494
TI  - Pathogens of zoonotic and biological importance in roe deer (Capreolus
      capreolus): Seroprevalence in an agro-system population in France.
AB  - Antibody prevalence for several infectious and parasitic diseases in a population
      of roe deer (Capreolus capreolus) inhabiting a mixed agricultural landscape
      (south of France) has been analyzed. Serological analyses with ELISA in 245
      animals captured from 2008 to 2012 has been performed. We found a high prevalence
      of Toxoplasma gondii (46.4%), Chlamydophila abortus (17.27%) and Coxiella
      burnetii (11.26%) compared to other studies in Europe. Seroprevalence varied
      strongly among years for T. gondii (27-91%), C. abortus (0-42%) and C. burnetii
      (0-27%). T. gondii prevalence was lower in juvenile females, compared to juvenile
      males and adults of both sexes. Other pathogens had low prevalences: Neospora
      caninum (1.56%), Bovine herpesvirus 1 (1.17%, 2008/09; 1.1%, 2010/11), Mycoplasma
      agalactiae (1.45%, 2009/10), Mycobacterium avium subsp. paratuberculosis (0.9%)
      and Slow viruses (CAEV-MVV) (0.15%, 2008/10; 0%, 2011/12). Antibodies to
      bluetongue virus and pestiviruses were not found in any individual. 

PMID- 24576495
TI  - Midterm failure after endovascular treatment of a persistent sciatic artery
      aneurysm.
AB  - Persistent sciatic artery (PSA) is a rare arterial embryologic malformation that
      tends to present early atherosclerotic degeneration such as aneurysmal formation.
      Open surgical treatment of PSA aneurysms has been considered as the gold standard
      but endovascular techniques have been recently proposed in the literature. We
      report the case of a 65-year-old man, diagnosed with a PSA aneurysm on peripheral
      thromboembolic complications. We achieved an endovascular repair with a covered
      stent. Despite an uneventful postoperative course, the covered stent demonstrated
      fracture and thrombosis 6 months after implantation without any symptoms. 

PMID- 24576497
TI  - Beyond leadership: political strategies for coordination in health policies.
AB  - Health in All Policies (HiAP) promises to improve population health by harnessing
      the energies and activities of various sectors. Nevertheless, it faces well
      documented bureaucratic obstacles and appears to require intersectoral governance
      if it is to be established. The basic problems of establishing intersectoral
      governance for HiAP are known to public administration and political science. On
      reading that literature, we find that the difficulty of establishing
      intersectoral governance for HiAP breaks down into two kinds of problems: that of
      establishing coordinated actions at all (coordination); and ensuring that they
      endure in changed political circumstances (durability). We further find that
      policymakers' solutions fall into three categories: visible ones of political
      will (e.g., plans and targets); bureaucratic changes such as the introduction of
      Health Impact Assessment or reorganization; and indirect methods such as data
      publication and support from outside groups to put pressure on the government. It
      can seem that Health in All Policies, like much of public health, depends on
      effective and committed policymakers but is vulnerable to changing political
      winds. The three kinds of strategies suggest how policymakers can, and do, create
      intersectoral governance that functions and persists, expanding the range of
      effective policy recommendations. 

PMID- 24576496
TI  - Conformational changes in dopamine transporter intracellular regions upon cocaine
      binding and dopamine translocation.
AB  - The dopamine transporter (DAT), a member of the neurotransmitter:sodium symporter
      family, mediates the reuptake of dopamine at the synaptic cleft. DAT is the
      primary target for psychostimulants such as cocaine and amphetamine. We
      previously demonstrated that cocaine binding and dopamine transport alter the
      accessibility of Cys342 in the third intracellular loop (IL3). To study the
      conformational changes associated with the functional mechanism of the
      transporter, we made cysteine substitution mutants, one at a time, from Phe332 to
      Ser351 in IL3 of the background DAT construct, X7C, in which 7 endogenous
      cysteines were mutated. The accessibility of the 20 engineered cysteines to polar
      charged sulfhydryl reagents was studied in the absence and presence of cocaine or
      dopamine. Of the 11 positions that reacted with methanethiosulfonate ethyl
      ammonium, as evidenced by inhibition of ligand binding, 5 were protected against
      this inhibition by cocaine and dopamine (S333C, S334C, N336C, M342C and T349C),
      indicating that reagent accessibility is affected by conformational changes
      associated with inhibitor and substrate binding. In some of the cysteine mutants,
      transport activity is disrupted, but can be rescued by the presence of zinc, most
      likely because the distribution between inward- and outward-facing conformations
      is restored by zinc binding. The experimental data were interpreted in the
      context of molecular models of DAT in both the inward- and outward-facing
      conformations. Differences in the solvent accessible surface area for individual
      IL3 residues calculated for these states correlate well with the experimental
      accessibility data, and suggest that protection by ligand binding results from
      the stabilization of the outward-facing configuration. Changes in the residue
      interaction networks observed from the molecular dynamics simulations also
      revealed the critical roles of several positions during the conformational
      transitions. We conclude that the IL3 region of DAT undergoes significant
      conformational changes in transitions necessary for both cocaine binding and
      substrate transport. 

PMID- 24576498
TI  - Waiting time prioritisation for specialist services in Italy: the homogeneous
      waiting time groups approach.
AB  - The demand for referrals and diagnostic procedures in Italy has been rising
      constantly in recent years, making access to diagnostic services increasingly
      difficult with significant waiting times. A number of Health Authorities (known
      as Local Health Units) have responded by implementing formalised waiting-time
      prioritisation tools, giving rise to what are known as Homogeneous Waiting Groups
      (HWGs). The study describes the implementation of the HWG approach in Italy. This
      represents a promising tool for improving the prioritisation of patients waiting
      to see a specialist or to receive a diagnostic test. The study of the Italian HWG
      experience provides useful insights to improve the outpatient referral process
      for those countries where the demand prioritisation policies have focused more on
      inpatient care than outpatient specialist care and diagnostic services. 

PMID- 24576499
TI  - Blood biochemical profile of very preterm infants before and after trophic
      feeding with exclusive human milk or with formula milk.
AB  - OBJECTIVES: To determine whether feeding type of trophic feeds affect
      haematological and biochemical markers in the very preterm infant. DESIGN AND
      METHODS: Fifty-six very preterm infants were enrolled in this retrospective study
      (30 infants were included in the only human milk-fed group and 26 in the formula
      fed group). Routine haematological and biochemical variables were collected in
      both groups on days 1 and 4 of life and fourteen serum markers were measured.
      RESULTS: There were no significant differences between the two groups before
      starting trophic feeds. After starting trophic feeds, sodium and lactate levels
      were significantly higher in the human milk-fed group compared with those
      measured in the formula-fed group. CONCLUSION: The study demonstrates that
      supplementation of minimal enteral feeding with human milk does affect
      biochemical profiles in very preterm infants. Small amounts of enteral feedings
      of formula and/or human milk may result in different metabolic responses; these
      differences are reflected by different serum biochemistries.

PMID- 24576500
TI  - Impact of prostate-specific antigen screening: building confidence.

PMID- 24576501
TI  - On the way toward better evidence for minimally invasive treatment of pelvic
      organ prolapse.

PMID- 24576503
TI  - Immunomodulatory factors and infectious agents associated with the hepatic gene
      expression of the IGF system in nursery pigs.
AB  - Recent findings suggest there is a complex interaction between the IGF system and
      the inflammatory immune response. The objective of this study was to determine
      whether gene expression of growth factors (IGF-1, IGF-binding protein-3 (IGFBP-3)
      and growth hormone receptors (GHR)) in the liver is associated with gene
      expression of immunomodulators in the liver, including C-reactive protein (CRP),
      serum amyloid A (SAA), haptoglobin (Hp), interferon-alpha (IFN-alpha), IFN-gamma,
      tumour necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, IL-6, IL-10 and
      IL-18, as well as with the presence of Salmonella spp., Lawsonia intracellularis,
      Brachyspira spp., enterotoxigenic Escherichia coli, methicillin-resistant
      Staphylococcus aureus, swine influenza virus, and porcine reproductive and
      respiratory syndrome virus (PRRSV) in nursery pigs (n=74) from commercial farms
      (n=4). Gene expression was quantified using reverse transcription quantitative
      PCR (RT-qPCR) and the data were modelled using logistic regression methods. Pigs
      with elevated IGF-1 expression were less likely to have increased expression of
      TNF-alpha (odds ratio (OR)=0.14, P<0.01) and IL-18 (OR=0.19, P<0.05), and less
      likely to be colonized with PRRSV (OR=0.03, P<0.01). Pigs with increased
      expression of IGFBP-3 were more likely to have elevated IL-6 expression (OR=8.5,
      P<0.05). It was also observed that IGFBP-3 and IGF-1 were significantly
      associated when Hp expression was low (OR=30, P<0.05), but this association was
      not significant when Hp expression was high (P=0.54). Pigs with increased
      expression of GHR were less likely to have elevated expression of SAA (OR=0.01,
      P<0.05) and IL-1beta (OR=0.03, P<0.05), but more likely to have increased
      expression of CRP (OR=290, P<0.01). Overall, there appears to be an inverse
      association between the hepatic expression of the IGF system (IGF-1, IGFBP-3,
      GHR) and certain cytokines (IL-1beta, IL-18, TNF-alpha) and acute-phase proteins
      (SAA, Hp). 

PMID- 24576502
TI  - Quality assessment of partial nephrectomy complications reporting using EAU
      standardised quality criteria.
AB  - CONTEXT: A standardised system to report outcomes and complications of urologic
      procedures has recently been proposed by an ad hoc European Association of
      Urology (EAU) Guidelines panel. To date, no studies have used these criteria to
      evaluate the quality of reports of outcomes and complications after partial
      nephrectomy (PN). OBJECTIVE: To address the quality of reporting of PN
      complications. DESIGN, SETTING, AND PARTICIPANTS: A systematic review of papers
      reporting outcomes of PN was conducted through the electronic search of
      databases, including Medline, PubMed, Embase, Scopus, and the Cochrane Database
      of Systematic Reviews. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Analysis
      was carried out on structured forms. The quality criteria that the EAU Working
      Group proposed for reporting complications were recorded for each paper, and
      adherence to the Martin criteria was assessed. RESULTS AND LIMITATIONS:
      Standardised criteria to report and grade complications were used in 71 out of
      204 evaluable studies (34.8%). Only six studies (2.9%) fulfilled all criteria
      that the EAU Guidelines Office ad hoc panel proposed. The mean number did not
      change significantly by time or by surgical approach used. The most underreported
      criteria (in <50% of the studies) were who collected the data (18.6%), whether he
      or she were involved in the treatment (13.7%), duration of follow-up (47.1%),
      mortality data and causes of death (33.8%), definition of procedure-specific
      complications (39.2), separate reporting of intra- and postoperative
      complications (45.1%), complication severity or grade (32.4%), risk factors
      analysis (44.1%), readmission rates (12.7%), and percentage of patients lost to
      follow-up (6.9%). The mean number fulfilled was 6.5 +/- 2.9 (mean plus or minus
      standard deviation) and did not change significantly by time or by surgical
      approach used. CONCLUSIONS: The only way to improve the quality of the surgical
      scientific literature and to allow sound comparisons among different approaches,
      especially with the lack of randomised trials, is the use of more rigorous
      methodology than the one recently proposed to report outcomes and complications.
      PATIENT SUMMARY: A rigorous methodology is mandatory when surgeons report about
      complications after surgery. Otherwise, the rate of adverse events is
      underestimated.

PMID- 24576504
TI  - Assessment of the sensitivity of the gamma-interferon test and the single
      intradermal comparative cervical test for the diagnosis of bovine tuberculosis
      under field conditions.
AB  - In some French departements, the eradication of bovine tuberculosis is incomplete
      and usual skin tests [single intradermal tuberculin test (SIT) and single
      intradermal comparative cervical test (SICCT)] have poor specificity due to cross
      reactions with non-pathogenic mycobacteria, causing economic losses. In Cote d'Or
      (Burgundy, France), an experimental serial testing scheme based on the
      combination of SICCT and gamma-interferon (IFN-gamma) tests has been initiated in
      order to shorten the interval between suspicion and its invalidation in herds
      with false-positive results to skin tests. Our aim was to assess the scheme's
      sensitivity and to compare it to the sensitivity of the screening scheme
      recommended by the European Commission. Our study included 1768 animals from Cote
      d'Or. The sensitivities of both schemes were estimated using a Bayesian approach.
      The individual sensitivity of the IFN-gamma test [88.1%, 95% credibility interval
      (CrI) 72.8-97.5] was not significantly different from individual SICCT
      sensitivity (80.3%, 95% CrI 61.6-98.0) and individual SIT sensitivity (84.2%, 95%
      CrI 59.0-98.2). The individual specificity of the IFN-gamma test was 62.3% (95%
      CrI 60.2-64.5). No significant difference could be demonstrated between the
      sensitivities of the serial testing scheme used in Cote d'Or (73.1%, 95% CrI 41.1
      100) and the European Union serial testing scheme (70.1%, 95% CrI 31.5-100.0).

PMID- 24576505
TI  - Post-hysterectomy dyspareunia.
AB  - When appropriately performed, hysterectomy most often contributes substantially
      to quality of life. Postoperative morbidity is minimal, in particular after
      minimally invasive surgery. In a minority of women, pain during intercourse is
      one of the more long-lasting sequelae of the procedure. Complete evaluation and
      treatment of this complication requires a thorough understanding of the status
      and function of neighboring organ systems and structures (urinary system,
      gastrointestinal tract, and pelvic and hip muscle groups). Successful resolution
      of dyspareunia often may be facilitated with review of the patient's previous
      degree of comfort during sex and the nature of her relationship with her partner.
      Repeat surgery is needed in a small minority of patients. 

PMID- 24576506
TI  - How children and adults learn to intercept moving gaps.
AB  - We used an immersive virtual environment to examine how children and adults learn
      to intercept moving gaps and whether children and adults benefit from variability
      of practice. Children (10- and 12-year-olds) and adults attempted to bicycle
      between two moving vehicle-size blocks without stopping. In Experiment 1, block
      motions were timed such that if participants maintained a constant speed, they
      would intercept the gap between the blocks. By the last set of intersections,
      adults learned to maintain a constant speed throughout the approach to the
      intersection, 12-year-olds exhibited less variability in time-to-spare when they
      intercepted the blocks, and 10-year-olds exhibited no significant change across
      intersection sets. In Experiment 2, block motions during the first eight
      intersections were timed such that participants needed to either speed up or slow
      down on all intersections or needed to speed up on half and slow down on half of
      the intersections. On the last four intersections, all age groups encountered a
      novel block timing in which no adjustment in speed was necessary to intercept the
      blocks. The adults performed well regardless of whether they experienced
      consistent or variable block timings. The 10-year-olds in the variable condition
      performed better on slow-down trials than their peers in the slow-down condition
      but performed worse on speed-up trials than their peers in the speed-up
      condition. Discussion focuses on possible developmental changes in reliance on
      perceptually available and remembered information in complex perception-action
      tasks. 

PMID- 24576507
TI  - HCC cells with high levels of Bcl-2 are resistant to ABT-737 via activation of
      the ROS-JNK-autophagy pathway.
AB  - The Bcl-2 inhibitor ABT-737 has shown promising antitumor efficacy in vivo and in
      vitro. However, some reports have demonstrated that HCC cells are resistant to
      ABT-737, and the corresponding molecular mechanisms of this resistance are not
      well known. In this study, we found that HCC cells with high levels of Bcl-2 were
      markedly resistant to ABT-737 compared to HCC cells with low levels of Bcl-2. In
      HCC cells with high levels of Bcl-2 (such as HepG2 cells), ABT-737 induced
      protective autophagy via the sequential triggering of reactive oxygen species
      (ROS) accumulation, short-term activation of JNK, enhanced phosphorylation of Bcl
      2, and dissociation of Beclin 1 from the Bcl-2/Beclin 1 complex. Moreover,
      autophagy suppressed the overactivation of the ROS-JNK pathway and protected
      against apoptosis. In HCC cells with low levels of Bcl-2 (i.e., Huh7 cells), ABT
      737 induced apoptosis via the sequential stimulation of ROS, sustained activation
      of JNK, enhanced translocation of Bax from the cytosol to the mitochondria, and
      release of cytochrome c. In sum, this study indicated that the activation of the
      ROS-JNK-autophagy pathway may be an important mechanism by which HCC cells with
      high levels of Bcl-2 are resistant to ABT-737. 

PMID- 24576508
TI  - Infant perception of audio-visual speech synchrony in familiar and unfamiliar
      fluent speech.
AB  - We investigated the effects of linguistic experience and language familiarity on
      the perception of audio-visual (A-V) synchrony in fluent speech. In Experiment 1,
      we tested a group of monolingual Spanish- and Catalan-learning 8-month-old
      infants to a video clip of a person speaking Spanish. Following habituation to
      the audiovisually synchronous video, infants saw and heard desynchronized clips
      of the same video where the audio stream now preceded the video stream by 366,
      500, or 666 ms. In Experiment 2, monolingual Catalan and Spanish infants were
      tested with a video clip of a person speaking English. Results indicated that in
      both experiments, infants detected a 666 and a 500 ms asynchrony. That is, their
      responsiveness to A-V synchrony was the same regardless of their specific
      linguistic experience or familiarity with the tested language. Compared to
      previous results from infant studies with isolated audiovisual syllables, these
      results show that infants are more sensitive to A-V temporal relations inherent
      in fluent speech. Furthermore, the absence of a language familiarity effect on
      the detection of A-V speech asynchrony at eight months of age is consistent with
      the broad perceptual tuning usually observed in infant response to linguistic
      input at this age.

PMID- 24576509
TI  - Laparoscopic virtual reality simulator and box trainer in gynecology.
AB  - OBJECTIVE: To investigate whether a virtual reality simulator (LapSim) and
      traditional box trainer are effective tools for the acquisition of basic
      laparoscopic skills, and whether the LapSim is superior to the box trainer in
      surgical education. METHODS: In a study at Ege University School of Medicine,
      Izmir, Turkey, between September 2008 and March 2013, 40 first- and second-year
      residents were randomized to train via the LapSim or box trainer for 4 weeks, and
      20 senior residents were allocated to a control group. All 3 groups performed
      laparoscopic bilateral tubal ligation. Video records of each operation were
      assessed via the general rating scale of the Objective Structured Assessment of
      Laparoscopic Salpingectomy and by operation time in seconds. RESULTS: Compared
      with the control group, the LapSim and box trainer groups performed significantly
      better in total score (P<0.01 and P<0.01, respectively) and time (P=0.03 and
      P=0.01, respectively). There were no differences between the LapSim and box
      trainer groups. CONCLUSION: Novice residents who trained on a LapSim or box
      trainer performed better live laparoscopies than residents who trained via
      standard clinical surgical education. Training with a virtual reality simulator
      or box trainer should be considered before actual laparoscopic procedures are
      carried out.

PMID- 24576510
TI  - Vitamin D deficiency and coronary artery disease: a review of the evidence.
AB  - Coronary artery disease remains the leading cause of death in developed countries
      despite significant progress in primary prevention and treatment strategies.
      Older patients are at particularly high risk of poor outcomes following acute
      coronary syndrome and impaired nutrition, including low vitamin D levels, may
      play a role. The extraskeletal effects of vitamin D, in particular, its role in
      maintaining a healthy cardiovascular system are receiving increased attention.
      Longitudinal studies have demonstrated increased cardiovascular mortality and
      morbidity associated with vitamin D deficiency. Low vitamin D levels have been
      linked to inflammation, higher coronary artery calcium scores, impaired
      endothelial function and increased vascular stiffness. However, so far, few
      randomized controlled trials have investigated the potential benefits of vitamin
      D supplementation in preventing cardiovascular events, and most available trials
      have tested low doses of supplementation in relatively low-risk populations.
      Whether vitamin D supplementation will be beneficial among patients with coronary
      artery disease, including high risk older patients presenting with acute coronary
      syndrome, is unknown and warrants further investigation. 

PMID- 24576511
TI  - Rechanneling the cardiac proarrhythmia safety paradigm: a meeting report from the
      Cardiac Safety Research Consortium.
AB  - This white paper provides a summary of a scientific proposal presented at a
      Cardiac Safety Research Consortium/Health and Environmental Sciences
      Institute/Food and Drug Administration-sponsored Think Tank, held at Food and
      Drug Administration's White Oak facilities, Silver Spring, MD, on July 23, 2013,
      with the intention of moving toward consensus on defining a new paradigm in the
      field of cardiac safety in which proarrhythmic risk would be primarily assessed
      using nonclinical in vitro human models based on solid mechanistic considerations
      of torsades de pointes proarrhythmia. This new paradigm would shift the emphasis
      from the present approach that strongly relies on QTc prolongation (a surrogate
      marker of proarrhythmia) and could obviate the clinical Thorough QT study during
      later drug development. These discussions represent current thinking and
      suggestions for furthering our knowledge and understanding of the public health
      case for adopting a new, integrated nonclinical in vitro/in silico paradigm, the
      Comprehensive In Vitro Proarrhythmia Assay, for the assessment of a candidate
      drug's proarrhythmic liability, and for developing a public-private collaborative
      program to characterize the data content, quality, and approaches required to
      assess proarrhythmic risk in the absence of a Thorough QT study. This paper seeks
      to encourage multistakeholder input regarding this initiative and does not
      represent regulatory guidance. 

PMID- 24576512
TI  - Rationale and design of Faith-based Approaches in the Treatment of Hypertension
      (FAITH), a lifestyle intervention targeting blood pressure control among black
      church members.
AB  - BACKGROUND: Uncontrolled hypertension (HTN) is a significant public health
      problem among blacks in the United States. Despite the proven efficacy of
      therapeutic lifestyle change (TLC) on blood pressure (BP) reduction in clinical
      trials, few studies have examined their effectiveness in church-based settings-an
      influential institution for health promotion in black communities. METHODS: Using
      a cluster-randomized, 2-arm trial design, this study evaluates the effectiveness
      of a faith-based TLC intervention vs health education (HE) control on BP
      reduction among hypertensive black adults. The intervention is delivered by
      trained lay health advisors through group TLC sessions plus motivational
      interviewing in 32 black churches. Participants in the intervention group receive
      11 weekly TLC sessions targeting weight loss, increasing physical activity,
      fruit, vegetable and low-fat dairy intake, and decreasing fat and sodium intake,
      plus 3 monthly individual motivational interviewing sessions. Participants in the
      control group attend 11 weekly classes on HTN and other health topics delivered
      by health care experts. The primary outcome is change in BP from baseline to 6
      months. Secondary outcomes include level of physical activity, percent change in
      weight, and fruit and vegetable consumption at 6 months, and BP control at 9
      months. CONCLUSION: If successful, this trial will provide an alternative and
      culturally appropriate model for HTN control through evidence-based lifestyle
      modification delivered in churches by lay health advisors.

PMID- 24576514
TI  - Design and rationale of the TOTAL trial: a randomized trial of routine aspiration
      ThrOmbecTomy with percutaneous coronary intervention (PCI) versus PCI ALone in
      patients with ST-elevation myocardial infarction undergoing primary PCI.
AB  - BACKGROUND: A major limitation of primary percutaneous coronary intervention
      (PPCI) for the treatment of ST-elevation myocardial infarction (STEMI) is
      impaired microvascular perfusion due to embolization and obstruction of
      microcirculation with thrombus. Manual thrombectomy has the potential to reduce
      distal embolization and improve microvascular perfusion. Clinical trials have
      shown mixed results regarding thrombectomy. OBJECTIVE: The objective of this
      study is to evaluate the efficacy of routine upfront manual aspiration
      thrombectomy during PPCI compared with percutaneous coronary intervention alone
      in patients with STEMI. DESIGN: This is a multicenter, prospective, open,
      international, randomized trial with blinded assessment of outcomes. Patients
      with STEMI undergoing PPCI are randomized to upfront routine manual aspiration
      thrombectomy with the Export catheter (Medtronic CardioVascular, Santa Rosa, CA)
      or to percutaneous coronary intervention alone. The primary outcome is the
      composite of cardiovascular death, recurrent myocardial infarction, cardiogenic
      shock, or new or worsening New York Heart Association class IV heart failure up
      to 180 days. The trial uses an event-driven design and will recruit 10,700
      patients. SUMMARY: The TOTAL trial will determine the effect of routine manual
      aspiration thrombectomy during PPCI on clinically important outcomes.

PMID- 24576513
TI  - The effect of renal denervation added to standard pharmacologic treatment versus
      standard pharmacologic treatment alone in patients with resistant hypertension:
      rationale and design of the SYMPATHY trial.
AB  - The first studies on renal denervation (RDN) suggest that this treatment is
      feasible, effective, and safe in the short term. Presently available data are
      promising, but important uncertainties exist; therefore, SYMPATHY has been
      initiated. SYMPATHY is a multicenter, randomized, controlled trial in patients
      randomized to RDN in addition to usual care (intervention group) or to continued
      usual care (control group). Randomization will take place in a ratio of 2 to 1.
      At least 300 participants will be included to answer the primary objective.
      Sample size may be extended to a maximum of 570 to address key secondary
      objectives. The primary objective is to assess whether RDN added to usual care
      compared with usual care alone reduces blood pressure (BP) (ambulatory daytime
      systolic BP) in subjects with an average daytime systolic BP >=135, despite use
      of >=3 BP-lowering agents, 6 months after RDN. Key secondary objectives are
      evaluated at 6 months and at regular intervals during continued follow-up and
      include the effect of RDN on the use of BP-lowering agents, in different
      subgroups (across strata of estimated glomerular filtration rate and of baseline
      BP), on office BP, quality of life, and cost-effectiveness. 

PMID- 24576515
TI  - DETermination of the role of OXygen in suspected Acute Myocardial Infarction
      trial.
AB  - BACKGROUND: The use of supplemental oxygen in the setting of suspected acute
      myocardial infarction (AMI) is recommended in international treatment guidelines
      and established in prehospital and hospital clinical routine throughout the
      world. However, to date there is no conclusive evidence from adequately designed
      and powered trials supporting this practice. Existing data are conflicting and
      fail to clarify the role of supplemental oxygen in AMI. METHODS: A total of 6,600
      normoxemic (oxygen saturation [SpO2] >=90%) patients with suspected AMI will be
      randomly assigned to either supplemental oxygen 6 L/min delivered by Oxymask
      (MedCore Sweden AB, Kista, Sweden) for 6 to 12 hours in the treatment group or
      room air in the control group. Patient inclusion and randomization will take
      place at first medical contact, either before hospital admission or at the
      emergency department. The Swedish Web-system for Enhancement and Development of
      Evidence-based care in Heart disease Evaluated According to Recommended Therapies
      registry will be used for online randomization, allowing inclusion of a broad
      population of all-comers. Follow-up will be carried out in nationwide health
      registries and Swedish Web-system for Enhancement and Development of Evidence
      based care in Heart disease Evaluated According to Recommended Therapies. The
      primary objective is to evaluate whether oxygen reduces 1-year all-cause
      mortality. Secondary end points include 30-day mortality, major adverse cardiac
      events, and health economy. Prespecified subgroups include patients with
      confirmed AMI and certain risk groups. In a 3-month pilot study, the study
      concept was found to be safe and feasible. CONCLUSION: The need to clarify the
      uncertainty of the role of supplemental oxygen therapy in the setting of
      suspected AMI is urgent. The DETO2X-AMI trial is designed and powered to address
      this important issue and may have a direct impact on future recommendations.

PMID- 24576516
TI  - Design and rationale of Global Registry on Long-Term Oral Antithrombotic
      Treatment in Patients with Atrial Fibrillation: a global registry program on long
      term oral antithrombotic treatment in patients with atrial fibrillation.
AB  - BACKGROUND: Atrial fibrillation (AF) is the most common cardiac arrhythmia,
      affecting 1% to 2% of the population and raising the risk of stroke 5-fold. Until
      recently, the only treatment choices for stroke prevention in patients with AF
      have been vitamin K antagonists (VKA) or antiplatelet drugs. With approval of
      novel oral anticoagulants (NOACs) antithrombotic treatment, patterns are
      changing. The Global Registry on Long-Term Oral Antithrombotic Treatment in
      Patients with Atrial Fibrillation is designed to investigate patient
      characteristics influencing choice of antithrombotic treatment of stroke
      prevention in patients with nonvalvular AF and to collect data on outcomes of
      antithrombotic therapy in clinical practice. METHODS: The GLORIA-AF is a large,
      international, observational registry involving patients with newly diagnosed
      nonvalvular AF at risk for stroke, enrolling up to 56,000 patients in nearly 50
      countries. We will collect and analyze data from routine care using an inception
      cohort design. Phase I includes patients before approval of NOACs. Phase II,
      beginning early after approval of dabigatran, monitors dabigatran safety and
      addresses potential channeling across treatment options based on propensity
      scoring to assess comparability of baseline characteristics of patients treated
      with dabigatran or VKA. Phase III entails analysis of large treatment groups,
      adjusting for differences in propensity score, to provide information about the
      relative effectiveness and safety of NOACs and VKA in routine clinical care.
      CONCLUSIONS: Novel features of this registry program will add data from clinical
      practice to those from randomized trials to expand knowledge of antithrombotic
      treatment in patients with AF.

PMID- 24576517
TI  - The design and rationale for the Acute Medically Ill Venous Thromboembolism
      Prevention with Extended Duration Betrixaban (APEX) study.
AB  - Randomized clinical trials have identified a population of acute medically ill
      patients who remain at risk for venous thromboembolism (VTE) beyond the standard
      duration of therapy and hospital discharge. The aim of the APEX study is to
      determine whether extended administration of oral betrixaban (35-42 days) is
      superior to a standard short course of prophylaxis with subcutaneous enoxaparin
      (10 +/- 4 days followed by placebo) in patients with known risk factors for post
      discharge VTE. Patients initially are randomized to receive either betrixaban or
      enoxaparin (and matching placebo) in a double dummy design. Following a standard
      duration period of enoxaparin treatment (with placebo tablets) or betrixaban
      (with placebo injections), patients receive only betrixaban (or alternative
      matching placebo). Patients are considered for enrollment if they are older than
      40 years, have a specified medical illness, and restricted mobility. They must
      also meet the APEX criteria for increased VTE risk (aged >=75 years, baseline D
      Dimer >=2* upper the limit of "normal", or 2 additional ancillary risk factors
      for VTE). The primary efficacy end point is the composite of asymptomatic
      proximal deep venous thrombosis, symptomatic deep venous thrombosis, non-fatal
      (pulmonary embolus) pulmonary embolism, or VTE-related death through day 35. The
      primary safety outcome is the occurrence of major bleeding. We hypothesize that
      extended duration betrixaban VTE prophylaxis will be safe and more effective than
      standard short duration enoxaparin in preventing VTE in acute medically ill
      patients with known risk factors for post hospital discharge VTE. 

PMID- 24576518
TI  - Rationale and design of the familial hypercholesterolemia foundation CAscade
      SCreening for Awareness and DEtection of Familial Hypercholesterolemia registry.
AB  - BACKGROUND: Familial hypercholesterolemia (FH) is a hereditary condition caused
      by various genetic mutations that lead to significantly elevated low-density
      lipoprotein cholesterol levels and resulting in a 20-fold increased lifetime risk
      for premature cardiovascular disease. Although its prevalence in the United
      States is 1 in 300 to 500 individuals, <10% of FH patients are formally
      diagnosed, and many are not appropriately treated. Contemporary data are needed
      to more fully characterize FH disease prevalence, treatment strategies, and
      patient experiences in the United States. DESIGN: The Familial
      Hypercholesterolemia Foundation (a patient-led nonprofit organization) has
      established the CAscade SCreening for Awareness and DEtection of Familial
      Hypercholesterolemia (CASCADE FH) Registry as a national, multicenter initiative
      to identify US FH patients, track their treatment, and clinical and patient
      reported outcomes over time. The CASCADE FH will use multiple enrollment
      strategies to maximize identification of FH patients. Electronic health record
      screening of health care systems will provide an efficient mechanism to identify
      undiagnosed patients. A group of specialized lipid clinics will enter baseline
      and annual follow-up data on demographics, laboratory values, treatment, and
      clinical events. Patients meeting prespecified low-density lipoprotein or total
      cholesterol criteria suspicious for FH will have the opportunity to self-enroll
      in an online patient portal with information collected directly from patients
      semiannually. Registry patients will be provided information on cascade screening
      and will complete an online pedigree to assist with notification of family
      members. SUMMARY: The Familial Hypercholesterolemia Foundation CASCADE FH
      Registry represents a novel research paradigm to address gaps in knowledge and
      barriers to comprehensive FH screening, identification, and treatment.

PMID- 24576519
TI  - Reperfusion times and in-hospital outcomes among patients with an isolated
      posterior myocardial infarction: insights from the National Cardiovascular Data
      Registry (NCDR).
AB  - BACKGROUND: A posterior myocardial infarction (PMI) is associated with
      significant morbidity and delays in recognition may prevent the timely
      revascularization of these patients. The present study sought to evaluate the
      reperfusion times and in-hospital outcomes among patients with an isolated PMI.
      METHODS: Clinical characteristics and reperfusion times were compared between
      those with an isolated PMI and those with all other ST-elevation myocardial
      infarctions (STEMI) in the NCDR ACTION-GWTG Registry from 2007 to 2012. Logistic
      generalized estimating equations were used to examine risk-adjusted mortality.
      RESULTS: Among 117,739 subjects with a STEMI, 824 (0.7%) had evidence of an
      isolated PMI. The median time between patient arrival and initial
      electrocardiogram was similar between those with an isolated PMI and those with a
      non-PMI STEMI (6 vs. 6 minutes, P = .48). However, the median time from initial
      electrocardiogram to percutaneous coronary intervention was significantly longer
      among subjects with a PMI (69 vs 61 minutes, P < .01) and fewer patients achieved
      a door-to-balloon time less than 90 minutes (83% vs 89%, P < .01). After
      multivariable adjustment, in-hospital mortality was similar for PMI patients
      compared to those with a non-PMI STEMI (AOR: 1.11, 95% CI: 0.83-1.50).
      CONCLUSION: The door-to-balloon times are significantly longer for those with an
      isolated PMI resulting in fewer patients receiving reperfusion within the
      guideline recommended time period. Ongoing educational initiatives to increase
      recognition of a PMI are needed to improve the reperfusion times and outcomes
      associated with this condition.

PMID- 24576520
TI  - Hospital patterns of medical management strategy use for patients with non-ST
      elevation myocardial infarction and 3-vessel or left main coronary artery
      disease.
AB  - BACKGROUND: Patients with non-ST-elevation myocardial infarction (NSTEMI) and
      three-vessel or left main coronary disease (3VD/LMD) have a high risk of long
      term mortality when treated with a medical management strategy (MMS) compared
      with revascularization. METHODS: We evaluated patterns of use and patient
      features across United States hospitals designated by MMS for NSTEMI patients
      with 3VD/LMD included in the ACTION Registry-GWTG from 2007-2012. RESULTS: A
      total of 42,535 patients without prior bypass surgery were found to have 3VD
      (>=50% stenosis in all major coronary vessels) or LMD (>=50% lesion) during in
      hospital angiography at 423 hospitals with percutaneous and surgical
      revascularization capabilities. Hospitals (n = 316) with an adequate volume (>=25
      NSTEMI patients treated) were stratified into tertiles defined by use of MMS;
      differences in patient characteristics and outcomes were analyzed. The proportion
      of NSTEMI patients treated with MMS at all hospitals varied from 16% to 19% each
      quarter and did not change significantly from 2007 to 2012 (P trend = .11). Among
      hospitals with adequate volume, the proportion of patients treated with MMS also
      varied widely (median 17.1%, range: 0.0-44.8%, P < .0001). Patient baseline
      characteristics, predicted mortality risk, actual in-hospital mortality rates,
      and discharge treatments were similar across hospital tertiles. CONCLUSIONS:
      Close to 20% of patients with NSTEMI and 3VD/LMD identified during in-hospital
      angiography are treated with MMS without revascularization in contemporary
      practice. Since the use of MMS varies widely across hospitals despite a
      relatively similar hospital-level case mix, these findings suggest that there is
      no standard threshold for the use of revascularization in NSTEMI patients with
      3VD/LMD.

PMID- 24576521
TI  - Changing prevalence, profile, and outcomes of patients with HIV undergoing
      cardiac surgery in the United States.
AB  - OBJECTIVES: Little is known about the prevalence, risk profile, and outcomes of
      patients with HIV undergoing cardiac surgery. This study was designed to evaluate
      clinical outcomes and national trends in this population in the United States.
      METHODS: Using data from the Nationwide Inpatient Sample from January 1, 2000, to
      December 31, 2010, prevalence, risk factors and clinical outcomes after cardiac
      surgery were quantified for patients with HIV. Cox proportional hazards models
      were used to evaluate the impact of HIV status on postoperative mortality, and
      weights used to estimate national trends. RESULTS: The prevalence of HIV in
      cardiac surgery patients doubled from 0.1% to 0.2% (P < .001), with 1,239 cases
      recorded out of a total of 810,940 over the study period. The proportion of HIV
      positive patients undergoing cardiac surgery for endocarditis decreased from
      31.8% to 8.2% (P = .016). Operative mortality in patients with HIV decreased from
      5.6% to 0.87% (P < .001) over the study period. HIV was not found to be an
      independent predictor of operative mortality in multivariate analysis (adjusted
      OR 0.88, 95% CI 0.64-1.2, P = .436), whereas earlier year of operation (adjusted
      OR 0.72, 95% CI 0.60-0.87, P < .001) and the presence of disease conditions
      related to HIV status (OR 2.4, 95% CI 1.5-3.8, P = .01) were independent
      predictors of operative mortality in patients with HIV. CONCLUSIONS: In
      contemporary practice HIV does not appear to be associated with incremental
      operative mortality, except in patients with clinical disorders related to their
      HIV status.

PMID- 24576522
TI  - Associations between atrial fibrillation and early outcomes of patients with
      heart failure and reduced or preserved ejection fraction.
AB  - BACKGROUND: The relative impact of atrial fibrillation on early outcomes of
      patients with heart failure with reduced or preserved ejection fraction (EF) is
      unknown. METHODS: We conducted a retrospective cohort study of clinical registry
      data linked to Medicare claims for patients with heart failure with reduced or
      preserved EF stratified by presence of atrial fibrillation at admission. Outcomes
      of interest were all-cause mortality and readmission at 30days. We used Kaplan
      Meier methods to estimate mortality and calculated cumulative incidence estimates
      of readmission. We used Cox proportional hazards models to examine associations
      between atrial fibrillation and 30-day outcomes. RESULTS: Among 66,357 patients
      admitted to 283 hospitals between January 2001 and March 2006, 46% had atrial
      fibrillation (44% of patients with reduced EF and 48% of patients with preserved
      EF). After adjustment for other patient characteristics, atrial fibrillation was
      associated with a modestly higher risk of 30-day mortality (HR, 1.08; 95% CI,
      1.03-1.14) and readmission (HR, 1.06; 95% CI, 1.02-1.11). In subgroup analyses,
      atrial fibrillation was associated with a higher risk of 30-day mortality (HR,
      1.16; 95% CI, 1.08-1.25) among patients with preserved EF but not among patients
      with reduced EF. The association of atrial fibrillation with readmission did not
      differ by heart failure type (P=.37 for the interaction). CONCLUSIONS: Atrial
      fibrillation was associated with higher 30-day mortality among patients with
      heart failure with preserved EF but not reduced EF. The association of atrial
      fibrillation with 30-day readmission was modest and did not differ by heart
      failure type.

PMID- 24576523
TI  - Age and sex differences in inhospital complication rates and mortality after
      percutaneous coronary intervention procedures: evidence from the NCDR((r)).
AB  - BACKGROUND: Older women experience higher complication rates and mortality after
      percutaneous coronary intervention (PCI) than men, but there is limited evidence
      about sex-based differences in outcomes among younger patients. We compared rates
      of complications and inhospital mortality by sex for younger and older PCI
      patients. METHODS: A total of 1,079,751 hospital admissions for PCI were
      identified in the CathPCI Registry((r)) from 2005 to 2008. Complication rates
      (general, bleeding, bleeding with transfusion, and vascular) and inhospital
      mortality after PCI were compared by sex and age (<55 and >=55 years). Analyses
      were adjusted for demographic and clinical factors and stratified by PCI type
      (elective, urgent, or emergency). RESULTS: Overall, 6% of patients experienced
      complications, and 1% died inhospital. Unadjusted complication rates were higher
      for women compared with men in both age groups. In risk-adjusted analyses,
      younger women (odds ratio 1.24, 95% CI 1.16-1.33) and older women (1.27, 1.09
      1.47) were more likely to experience any complication than similarly aged men.
      The increased risk persisted across complication categories and PCI type. Within
      age groups, risk-adjusted mortality was marginally higher for young women (1.19,
      1.00-1.41), but not for older women (1.03, 0.97-1.10). In analyses stratified by
      PCI type, young women had twice the mortality risk after an elective procedure as
      young men (2.04, 1.15-3.61). CONCLUSIONS: Women, regardless of age, experience
      more complications after PCI than men; young women are at increased mortality
      risk after an elective PCI. Identifying strategies to reduce adverse outcomes,
      particularly for women younger than 55 years, is important.

PMID- 24576524
TI  - The impact of residual coronary lesions on clinical outcomes after percutaneous
      coronary intervention: Residual SYNTAX score after percutaneous coronary
      intervention in patients from the Efficacy of Xience/Promus versus Cypher in
      rEducing Late Loss after stENTing (EXCELLENT) registry.
AB  - BACKGROUND: The SYNTAX score (SS) is used in preprocedural evaluation for
      percutaneous coronary intervention (PCI); it assesses the complexity of coronary
      lesions and predicts PCI outcome. However, the usefulness of the residual SS
      (rSS), which can be calculated after PCI and may reflect the completeness of
      revascularization, has not been fully investigated in an enriched PCI population.
      METHODS AND RESULTS: The baseline SS and rSS were determined in 5,088 patients
      (3,046 everolimus-eluting stents and 2,042 sirolimus-eluting stents) from the
      EXCELLENT registry. The primary end point was 1-year patient-oriented composite
      end point (POCE), comprising all-cause death, myocardial infarction, and repeat
      revascularization. The mean baseline SS was 13.6 +/- 9.1 and rSS was 4.7 +/- 6.5.
      Residual SS tertiles were defined as rSS = 0 (42.7%), 0 < rSS < 7 (29.9%), and
      rSS >= 7 (27.4%). Increasing rSS tertiles had increasing 1-year POCE rates (5.2%,
      8.1%, 12.4%; P < .001) mainly caused by the increase in repeat revascularization.
      Also, rSS was an independent predictor of 1-year POCE after multivariate analysis
      (P for trend < .001) and had better predictability in simple coronary lesions
      (baseline SS < 16). The clinical rSS, calculated by multiplying the rSS to a
      modified age, creatinine clearance, and ejection fraction score (age/ejection
      fraction + 1 for each 10 mL the creatinine clearance <60 mL/min), was also
      associated with 1-year POCE, with predictability similar to rSS (area under curve
      0.610 vs 0.607, P = .634). CONCLUSION: Greater residual coronary lesions after
      PCI with "limus" drug-eluting stent, as quantified by the rSS and the clinical
      rSS, are associated with increased risk of adverse cardiac events.

PMID- 24576525
TI  - Comparison of percutaneous coronary intervention for previously treated versus de
      novo culprit lesions in acute myocardial infarction patients: insights from the
      National Cardiovascular Data Registry.
AB  - BACKGROUND: Little is known about percutaneous coronary intervention (PCI)
      outcomes among patients presenting with an acute myocardial infarction (MI) with
      a history of prior PCI. Outcomes may differ depending on whether PCI is performed
      on a previously treated or de novo culprit lesion. METHODS: We examined ST
      segment elevation myocardial infarction (STEMI) and non-STEMI patients who
      underwent PCI in the CathPCI Registry from 2009 to 2012. We used multivariable
      logistic regression to compare adjusted in-hospital mortality between groups.
      RESULTS: Among 675,587 MI patients, 147,841 (22%) had a history of prior PCI;
      these patients were older and more frequently had co-morbid conditions yet had
      lower adjusted mortality compared with patients undergoing their first
      intervention (OR = 0.73, 95% CI = 0.70-0.76). Among patients with prior PCI,
      50,744 (34%) received intervention to a culprit lesion in a previously treated
      segment. Compared with patients with de novo culprit lesions, those with
      previously treated culprits were more likely to present with STEMI, but had lower
      mortality risk (OR = 0.88, 95% CI = 0.82-0.95) regardless of STEMI or non-STEMI
      presentation. Among previously treated patients, in-hospital mortality was not
      significantly different between those with prior drug-eluting versus bare metal
      stent-treated culprit lesions (OR = 0.95, 95% CI = 0.81-1.12). CONCLUSION:
      Despite greater co-morbidity burden, MI patients with prior PCI had lower
      mortality compared with patients undergoing their first intervention. Among
      patients with prior PCI, patients undergoing PCI to a previously treated culprit
      lesion were associated with lower mortality than those being intervened for a de
      novo culprit. A better understanding of these differences will help improve
      procedural strategies and outcomes of patients undergoing PCI of a previously
      treated lesion.

PMID- 24576526
TI  - Impact of baseline hemorrhagic risk on the benefit of bivalirudin versus
      unfractionated heparin in patients treated with coronary angioplasty: a meta
      regression analysis of randomized trials.
AB  - BACKGROUND: Bivalirudin significantly reduces 30-day major and minor bleeding
      compared with unfractionated heparin (UFH), while resulting in similar or lower
      rates of ischemic events in both patients with stable and unstable coronary
      disease undergoing percutaneous coronary intervention. We performed a meta
      analysis of randomized trials to evaluate the impact of bivalirudin compared with
      UFH, with or without glycoprotein IIb/IIIa receptor inhibitors (GPI), on the
      rates of mortality, myocardial infarction (MI), and major bleeding. METHODS: We
      searched electronic databases for randomized controlled trials with >100 patients
      comparing bivalirudin (+/-provisional GPI) with UFH with either routine or
      provisional GPI in patients undergoing percutaneous coronary intervention. The
      principal efficacy end points were mortality and MI within 30 day, whereas major
      bleeding was the principal safety end point. We assessed the benefit of
      bivalirudin for each efficacy end point relative to the baseline bleeding risk,
      using the control (UFH) major bleeding rate as proxy for that risk. RESULTS: A
      total of 12 randomized trials that enrolled 33,261 patients were included.
      Overall, there was no significant difference in mortality and MI between
      bivalirudin monotherapy and UFH (+/-GPI), whereas major bleeding was
      significantly lower with bivalirudin. Bivalirudin reduced major and minor
      bleeding across the entire bleeding risk spectrum. CONCLUSIONS: Bivalirudin
      significantly reduces major and minor bleeding regardless of the estimated
      baseline hemorrhagic risk.

PMID- 24576527
TI  - Prevalence of CYP2C19 variant alleles and pharmacodynamic variability of aspirin
      and clopidogrel in Native Americans.
AB  - BACKGROUND: The prevalence of variant alleles of the CYP2C19 gene has been
      determined for most population groups, but not Native Americans. Furthermore, the
      overall effectiveness of clopidogrel and aspirin has not been well studied in
      Native Americans, although this group has high mortality rates for cardiovascular
      disease and diabetes. METHODS: We recruited 50 volunteers from the Oglala Sioux
      Tribe with coronary artery disease taking aspirin and clopidogrel. Whole blood
      was collected for analysis using the VerifyNow P2Y12 and aspirin tests. Samples
      from the coronary artery disease patients and 50 additional tribal volunteers (n
      = 100 total) were genotyped for CYP2C19 variants *2, *3, and *17. RESULTS: The
      allele frequencies for CYP2C19*2 and CYP2C19*17 in the population group were 11%
      (95% CI 7%-16%) and 9% (95% CI 5%-13%), respectively. No subjects carried the
      CYP2C19*3 allele. The median PRU (P2Y12 reaction units) in the population group
      was 194 with wide variability (range 29-400). There was no significant effect of
      genotype on platelet aggregation as measured by the VerifyNow P2Y12 test (P =
      .77). The median ARU (aspirin reaction units) for the group was 437 (range 350
      659), and 73% had aspirin reaction unit values <550. CONCLUSIONS: The prevalence
      of variant CYP2C19 alleles is low in Native Americans of the Oglala Sioux Tribe
      compared with certain HapMap populations. The variable response to aspirin and
      clopidogrel in the Oglala Sioux Tribe is consistent with reported values for
      other groups as measured by the VerifyNow assay (Accumetrics, San Diego, CA).

PMID- 24576528
TI  - Reply to comment on: "a multicenter randomized comparison of paclitaxel-coated
      balloon catheter with conventional balloon angioplasty in patients with bare
      metal stent restenosis and drug-eluting stent restenosis".

PMID- 24576529
TI  - Comment on: "a multicenter randomized comparison of paclitaxel-coated balloon
      catheter with conventional balloon angioplasty in patients with bare-metal stent
      restenosis and drug-eluting stent restenosis".

PMID- 24576530
TI  - [Biofeedback and drug-resistant epilepsy: back to an earlier treatment?].
AB  - Biofeedback is a complementary non-pharmacological and non-surgical therapeutic
      developed over the last thirty years in the management of drug-resistant
      epilepsy. Biofeedback allows learning cognitive and behavioral strategies via a
      psychophysiological feedback loop. Firstly, this paper describes the different
      types of biofeedback protocols used for the treatment of drug-refractory epilepsy
      and their physiological justifications. Secondly, this paper analyzes the
      evidence of effectiveness, from a medical point of view, on reducing the numbers
      of seizures, and from a neurophysiological point of view, on the changing brain
      activity. Electroencephalography (EEG) biofeedback (neurofeedback) protocol on
      sensorimotor rhythms (SMR) has been investigated in many studies, the main
      limitation being small sample sizes and lack of control groups. The newer
      neurofeedback protocol on slow cortical potential (SCP) and galvanic skin
      response (GSR) biofeedback protocols have been used in a smaller number of
      studies. But, these studies are more rigorous with larger sized samples, matched
      control groups, and attempts to control the placebo effect. These protocols also
      open the way for innovative neurophysiological researches and may predict a
      renewal of biofeedback techniques. Biofeedback would have legitimacy in the field
      of clinical drug-resistant epilepsy at the interface between therapeutic and
      clinical neurophysiology. 

PMID- 24576531
TI  - Sorbitol non-fermenting shiga toxin-producing Escherichia coli in cattle on
      smallholdings.
AB  - We investigated faecal samples collected from the rectum of 518 cattle on 371
      randomly selected smallholdings in Bangladesh for the presence of sorbitol non
      fermenting (SN-F) shiga toxin-producing Escherichia coli (STEC). The SN-F
      isolates were tested for the presence of rfb O157, stx1, stx2, eae and hlyA genes
      by polymerase chain reaction (PCR). Seven SN-F isolates lacking these genes were
      profiled by pulsed-field gel electrophoresis (PFGE) to verify their clonality. SN
      F E. coli was identified in 44 [8.5%, 95% confidence interval (CI) 6.4-11.2]
      samples; of these, 28 (5.4%, 95% CI 3.8-7.7) had shiga toxin-producing strains,
      although only two carried the rfb O157 gene. Thirteen isolates carried the hlyA
      gene while 18 harboured the eae gene. Based on PFGE, six pulsotypes were observed
      among the seven isolates that had no virulence genes. To the best of our
      knowledge this is the first report on shiga toxin-producing E. coli from direct
      rectal faecal samples of cattle on smallholdings.

PMID- 24576532
TI  - Relapse prevention study of paliperidone extended-release tablets in Chinese
      patients with schizophrenia.
AB  - OBJECTIVES: The objective of this study was to evaluate the long-term efficacy,
      safety, and tolerability of paliperidone extended-release (pali ER), in Chinese
      patients with schizophrenia. METHODS: In this parallel-group, relapse prevention,
      phase-3 study (screening [14-day], pali ER open-label run-in [8-week] and
      stabilization [6-week] phases, and double-blind (DB) treatment [variable
      duration], and open-label extension phases [24-week]), 136/201 patients with
      schizophrenia were randomized (1:1) to pali ER (3-12 mg) or placebo during the DB
      phase. RESULTS: Final analysis showed that, out of 135 patients in ITT (DB)
      population, 71 (52.6%) had a relapse event, 45 (33.3%) were ongoing at the time
      the study was stopped, and 19 (14.1%) discontinued from the DB phase. Time to
      relapse (primary endpoint) favored pali ER (hazard ratio=5.23 [95% CI: 2.96,
      9.25], p <0.0001). Rate of relapses (55/71 [77.5%] placebo; 16/64 [25%] pali ER)
      and secondary endpoints (change from baseline in Positive And Negative Syndrome
      Scale [PANSS] and Clinical Global Impression - Severity Scores) were
      significantly lower (p<0.001) in pali ER group vs placebo, in favor of pali ER.
      More psychiatric-related treatment-emergent adverse events (TEAEs) occurred in
      placebo- (21.1%) than pali ER group (10.9%). Most common (>3%) TEAEs in placebo
      group were insomnia and schizophrenia (8.5% each), while in pali ER group were
      aggression and akathisia (4.7% each), and schizophrenia, tremor, nausea,
      amenorrhea, and salivary hypersecretion (3.1% each). All serious TEAEs were
      psychiatric-related (schizophrenia, aggression, completed suicide, auditory
      hallucination, suicide attempt) and more frequent in placebo- (11.3%) versus pali
      ER group (3.1%). Death and tardive dyskinesia-related discontinuation (n=1 each)
      occurred in placebo group. Body weight increase from run-in baseline was greater
      in pali ER group (mean increase: 3.90 kg) versus placebo (mean increase: 2.05
      kg). CONCLUSIONS: This study confirms the findings from earlier pali ER global
      relapse-prevention studies and demonstrates that pali ER treatment (3-12 mg) is
      efficacious over the long-term and significantly delays relapse in Chinese
      patients with schizophrenia. No new safety signals were detected in this
      population.

PMID- 24576533
TI  - Pleckstrin homology domain containing 6 protein (PLEKHA6) polymorphisms are
      associated with psychopathology and response to treatment in schizophrenic
      patients.
AB  - Pleckstrin homology domain (PH domain) comprises approximately 120 amino acids
      and is integrated in a wide range of proteins involved in intracellular signaling
      or as constituents of the cytoskeleton. This domain can bind phosphatidylinositol
      (3,4,5)-triphosphate and phosphatidylinositol (4,5)-biphosphate and proteins such
      as the betagamma-subunits of heterotrimeric G proteins and protein kinase C.
      Associations with psychiatric diseases have not been investigated yet. To
      identify genes involved in response to antipsychotics, mice were treated with
      haloperidol (1mg/kg, n = 11) or saline (n = 12) for one week. By analyzing
      microarray data, we observed an increase of pleckstrin homology domain containing
      6 (PLEKHA6) gene expression. Furthermore, we genotyped 263 schizophrenic
      patients, who were treated monotherapeutically with different antipsychotics
      within randomized-controlled trials. Psychopathology was measured weekly using
      the PANSS for a minimum of four and a maximum of twelve weeks. Correlations
      between PANSS subscale scores at baseline and PANSS improvement scores after four
      weeks of treatment and genotypes were calculated by using a linear model for all
      investigated SNPs. We found associations between four PLEKHA6 polymorphisms
      (rs17333933 (T/G), rs3126209 (C/T), rs4951338 (A/G) and rs100900571 (T/C)) and
      different PANSS subscales at baseline. Furthermore two different polymorphisms
      (rs7513240 (T/C), rs4951353 (A/G)) were found to be associated with therapy
      response in terms of a significant correlation with different PANSS improvement
      subscores after four weeks of antipsychotic treatment. Our observation of an
      association between genetic polymorphisms of a protein of the PH domain and
      psychopathology data in schizophrenic patients might be indicative for an
      involvement of PLEKHA6 in the pathophysiology of schizophrenia and the therapy
      response towards antipsychotics.

PMID- 24576534
TI  - Heteroresistance of Helicobacter pylori from the same patient prior to antibiotic
      treatment.
AB  - Antibiotic resistance among Helicobacter pylori strains has been increasing
      worldwide and has affected the efficacy of current treatments. The aim of this
      study was to evaluate whether treatment failure was due to the presence of
      antibiotic-susceptible and -resistant H. pylori simultaneously within the same
      host before eradication. In order to discover H. pylori with antibiotic
      heteroresistance in the same patient, we examined the antibiotic susceptibility
      of H. pylori isolated from 412 patients without H. pylori eradication. The E-test
      was used to determine the minimal inhibitory concentration of these strains. The
      results showed 19 (4.6%) of patients harbored antibiotic heteroresistant H.
      pylori, resistant to levofloxacin (5/19), clarithromycin (1/19) and metronidazole
      (16/19). Among them, three patients' isolates showed heteroresistance to two
      antibiotics. The genetic diversity of each isolate was evaluated by random
      amplified polymorphic DNA PCR and the results showed that only 1 patient' isolate
      (5.3%) had a different pattern while the others showed identical or similar
      fingerprinting patterns. Mutations in the genes responsible for antibiotic
      resistance were investigated by direct sequencing and compared between strains
      within each pair. All 5 levofloxacin-resistant isolates had mutations in GyrA at
      the QRDR region (N87 or D91). Strain 1571R with clarithromycin resistance had a
      A2042G substitution in its 23S rRNA. There were 15 metronidazole-resistant
      strains (100%) with isogenic variation of RdxA, and 6 strains (40%) contained
      FrxA variation (excluded pair 1159). These results suggest that the treatment
      failure of heteroresistant H. pylori mostly develops from high genomic variation
      of pre-existing strains through long term evolution rather than mixed infection
      with different strains. 

PMID- 24576535
TI  - Genetic and environmental influences on cardiovascular disease risk factors: a
      study of Chinese twin children and adolescents.
AB  - We evaluated the genetic and environmental contributions to metabolic
      cardiovascular risk factors and their mutual associations. Eight metabolic
      factors (body mass index, waist circumference, waist-to-hip ratio, systolic blood
      pressure, diastolic blood pressure, total serum cholesterol, serum triglycerides,
      and serum uric acid) were measured in 508 twin pairs aged 8-17 years from the
      Qingdao Twin Registry, China. Linear structural equation models were used to
      estimate the heritability of these traits, as well as the genetic and
      environmental correlations between them. Among boys, body mass index and uric
      acid showed consistently high heritability (0.49-0.81), whereas other traits
      showed moderate to high common environmental variance (0.37-0.73) in children (8
      12 years) and adolescents (13-17 years) except total cholesterol. For girls,
      moderate to high heritability (0.39-0.75) were obtained for six metabolic traits
      in children, while only two traits showed high heritability and others mostly
      medium to large common environmental variance in adolescents. Genetic
      correlations between the traits were strong in both boys and girls in children (r
      g = 0.64-0.99 between body mass index and diastolic blood pressure; r g = 0.71
      1.00 between body mass index and waist circumference), but decreased for
      adolescent girls (r g = 0.51 between body mass index and waist-to-hip ratio; r g
      = 0.55 between body mass index and uric acid; r g = 0.61 between body mass index
      and systolic blood pressure). The effect of genetic factors on most metabolic
      traits decreased from childhood to adolescence. Both common genetic and specific
      environmental factors influence the mutual associations among most of the
      metabolic traits. 

PMID- 24576536
TI  - An investigation of symptom burden and quality of life in Chinese chemo-naive
      advanced lung cancer patients by using the Instrument-Cloud QOL System.
AB  - OBJECTIVES: This study was designed to assess the disease-related symptom burden
      and quality of life (QOL) in Chinese chemo-naive advanced lung cancer patients.
      MATERIALS AND METHODS: Chemo-naive patients with stage III/IV lung cancer were
      enrolled. 43 centers from 16 provinces of China participated in the study.
      Functional Assessment of Cancer Therapy-Lung (FACT-L) scale and Cloud QOL System
      were applied in the study. RESULTS: 376 eligible patients were analyzed. The
      three most common and severe symptoms were appetite loss (84.3%, scored 2.46),
      breathing difficulty (79.0%, scored 2.56), and cough (75.5%, scored 2.81).
      Significant correlation was found between QOL and symptoms. Regression analysis
      of QOL indicated that almost every symptom item (except shortness of breath) was
      the negative indicator of QOL. Moreover, pulmonary diseases, pleural metastases
      and brain metastases had significant negative impact on both symptoms and QOL.
      Relatively poor performance status affected the QOL only, while cardiovascular
      diseases merely affected the symptoms. And patients with EGFR mutations had less
      symptom burden than those with wild-type EGFR. CONCLUSION: QOL evaluation by
      using the Cloud QOL System was feasible. Appetite loss, breathing difficulty and
      cough were the three most common and severe symptoms seen in Chinese chemo-naive
      advanced lung cancer patients. Almost all symptoms had negative impact on QOL.
      And some clinical characteristics could predict the symptoms and QOL.

PMID- 24576537
TI  - CYP26B1 promotes male germ cell differentiation by suppressing STRA8-dependent
      meiotic and STRA8-independent mitotic pathways.
AB  - Germ cell sex is defined by factors derived from somatic cells. CYP26B1 is known
      to be a male sex-promoting factor that inactivates retinoic acid (RA) in somatic
      cells. In CYP26B1-null XY gonads, germ cells are exposed to a higher level of RA
      than in normal XY gonads and this activates Stra8 to induce meiosis while male
      specific gene expression is suppressed. However, it is unknown whether meiotic
      entry by an elevated level of RA is responsible for the suppression of male-type
      gene expression. To address this question, we have generated Cyp26b1/Stra8 double
      knockout (dKO) embryos. We successfully suppressed the induction of meiosis in
      CYP26B1-null XY germ cells by removing the Stra8 gene. Concomitantly, we found
      that the male genetic program represented by the expression of NANOS2 and DNMT3L
      was totally rescued in about half of dKO germ cells, indicating that meiotic
      entry causes the suppression of male differentiation. However, half of the germ
      cells still failed to enter the appropriate male pathway in the dKO condition.
      Using microarray analyses together with immunohistochemistry, we found that KIT
      expression was accompanied by mitotic activation, but was canceled by inhibition
      of the RA signaling pathway. Taken together, we conclude that inhibition of RA is
      one of the essential factors to promote male germ cell differentiation, and that
      CYP26B1 suppresses two distinct genetic programs induced by RA: a Stra8-dependent
      meiotic pathway, and a Stra8-independent mitotic pathway. 

PMID- 24576540
TI  - Randomized trials, observational registries, and the foundations of evidence
      based medicine.
AB  - Although randomized trials and observational studies are used as the evidentiary
      basis of clinical practice guidelines, they are not always in agreement.
      Limitations in the process of randomization in the former and the selective
      referral of patients for treatment as a consequence of clinical "risk
      stratification" in the latter are underappreciated causes for these
      disagreements. As a result, neither is guaranteed to correctly quantify treatment
      benefit. This essay reviews the operational differences between these alternative
      evidentiary sources and shows how these differences can affect individual
      clinical decisions, population-based practice guidelines, and national health
      policy. In conclusion, the process of evidence-based medicine can be improved by
      independent agencies charged with the responsibility to identify and resolve
      these differences. 

PMID- 24576538
TI  - Over-expression of DMRT1 induces the male pathway in embryonic chicken gonads.
AB  - DMRT1 encodes a conserved transcription factor with an essential role in gonadal
      function. In the chicken, DMRT1 in located on the Z sex chromosome and is
      currently the best candidate master regulator of avian gonadal sex
      differentiation. We previously showed that knockdown of DMRT1 expression during
      the period of sexual differentiation induces feminisation of male embryonic
      chicken gonads. This gene is therefore necessary for proper testis development in
      the chicken. However, whether it is sufficient to induce testicular
      differentiation has remained unresolved. We show here that over-expression of
      DMRT1 induces male pathway genes and antagonises the female pathway in embryonic
      chicken gonads. Ectopic DMRT1 expression in female gonads induces localised SOX9
      and AMH expression. It also induces expression of the recently identified Z
      linked male factor, Hemogen (HEMGN). Masculinised gonads show evidence of cord
      like structures and retarded female-type cortical development. Furthermore,
      expression of the critical feminising enzyme, aromatase, is reduced in the
      presence of over-expressed DMRT1. These data indicate that DMRT1 is an essential
      sex-linked regulator of gonadal differentiation in avians, and that it likely
      acts via a dosage mechanism established through the lack of global Z dosage
      compensation in birds. 

PMID- 24576541
TI  - Comparison of outcomes in patients with ST-segment elevation myocardial
      infarction discharged on versus not on statin therapy (from the Harmonizing
      Outcomes With Revascularization and Stents in Acute Myocardial Infarction Trial).
AB  - Statin therapy is indicated after ST-segment elevation myocardial infarction
      (STEMI) to reduce recurrent ischemic events, but approximately 6% of patients
      with STEMI do not receive a statin prescription at discharge. This substudy aimed
      to define the clinical outcomes and patient characteristics associated with
      statin nonprescription after STEMI. We compared clinical, angiographic, and
      procedural characteristics and in-hospital, 30-day, 1-year, 2-year, and 3-year
      outcomes in 3,512 patients discharged after STEMI with and without (6%) statin
      prescriptions in the harmonizing outcomes with revascularization and stents in
      acute myocardial infarction trial (www.clinicaltrials.gov, NCT00433966). Statin
      nonprescription was associated with female sex, nonwhite race, previous bypass
      surgery, heart failure, renal impairment, anemia, thrombocytopenia, care in the
      United States, lower prescription rates of antiplatelets and neurohormonal
      antagonists, less percutaneous coronary intervention and stents, and, in 26% of
      cases, angiographically normal or nonobstructed coronary arteries. At every time
      point of follow-up after discharge, patients with no discharge statin
      prescription had significantly higher rates of net adverse clinical events, major
      adverse cardiac events, major bleeding unrelated to bypass surgery, and death.
      After multivariable adjustment, absence of a discharge statin prescription
      independently predicted 3-year major adverse cardiac event (hazard ratio 1.54,
      95% confidence interval 1.15 to 2.07, p=0.0037) and death (hazard ratio 2.30, 95%
      confidence interval 1.41 to 3.77, p=0.0009). In conclusion, within the framework
      of this randomized trial of patients presenting with STEMI, approximately 6% of
      patients were discharged without statin therapy. Absence of a discharge statin
      prescription after STEMI was an independent predictor of ischemic events
      including death.

PMID- 24576542
TI  - Definitions of periprocedural myocardial infarction as surrogates for
      catheterization laboratory quality or clinical trial end points.
AB  - A consensus on what constitutes a clinically meaningful periprocedural myocardial
      infarction (PMI) remains highly debated. We evaluated the accuracy of 2 PMI
      definitions currently implemented for quality outcome assessment and clinical
      trial end points. Patients who underwent elective percutaneous coronary
      intervention with normal baseline troponin-I and creatine kinase-MB were
      included. PMI was defined according to either the 2007 Task Force (National
      Cardiovascular Database Registry [NCDR] CathPCI Registry) definition or the
      updated 2012 Task Force definition. Multivariate analysis was performed for the
      end point of 1-year all-cause death or myocardial infarction (MI). Of the 7,333
      patients included, 31.9% and 2.1% were identified as having a PMI by NCDR or 2012
      definition, respectively. Mean age was 66+/-11 years; 66.8% were men, 1.4+/-0.9
      stents implanted per patient, 84.5% bivalirudin use, and 29.7 type C lesions.
      Death or MI occurred in 5.6% of NCDR and 6.6% of 2012 defined patients. Neither
      biomarker was independently associated with death or MI for either definition
      (NCDR odds ratio 1.1, 95% confidence interval 0.9 to 1.5, p=0.34; 2012 Task Force
      odds ratio 1.4, 95% confidence interval 0.7 to 3.0, p=0.38). Only a modest
      correlation exists for either definition to predict death or MI, which did not
      improve for the 2012 definition. In conclusion, PMI definitions currently used
      for catheterization lab quality metrics and those used for clinical trial end
      points have poor discrimination for adverse events. Although the 2012 definition
      drastically reduced the number of PMIs defined, it did not decrease the
      predictive accuracy over the NCDR definition.

PMID- 24576543
TI  - Cardiac restriction secondary to massive calcific deposits in the left
      ventricular cavity.
AB  - Described herein are clinical and necropsy findings in a 61-year-old woman with
      fatal left ventricular diastolic failure secondary to massive calcific deposits
      primarily within the left ventricular cavity. At age 3, an isthmic aortic
      coarctation was resected, and at age 44, a stenotic congenitally bicuspid aortic
      valve was replaced. The cause of the intracavitary calcific deposits remains
      unclear, but surgical resection of the deposits has been an effective form of
      therapy. 

PMID- 24576544
TI  - Effect of race/ethnicity on hypertension risk subsequent to gestational diabetes
      mellitus.
AB  - Gestational diabetes mellitus (GDM) prevalence is greater in racially/ethnically
      diverse groups compared with non-Hispanic white populations. Although race has
      been shown to modify other cardiovascular disease risk factors in postpartum
      women, the role of race/ethnicity on GDM and subsequent hypertension has yet to
      be examined. The aim of this study was to evaluate the impact of race/ethnicity
      in relation to GDM and subsequent hypertension in a retrospective analysis of
      women who delivered at Massachusetts General Hospital from 1998 to 2007.
      Multivariate analyses were used to determine the associations between GDM and (1)
      race/ethnicity, (2) hypertension, and (3) the interaction with hypertension and
      race/ethnicity. Women were monitored for a median of 3.8 years from the date of
      delivery. In our population of 4,010 women, GDM was more common in nonwhite
      participants (p<0.0001). GDM was also associated with hypertension subsequent to
      delivery after adjusting for age, race, parity, first-trimester systolic blood
      pressure, body mass index, maternal gestational weight gain, and preeclampsia
      (hazard ratio [HR] 1.75, 95% confidence interval [CI] 1.28 to 2.37, p=0.0004).
      Moreover, Hispanic (HR 3.25, 95% CI 1.85 to 5.72, p<0.0001) and white (HR 1.68,
      95% CI 1.10 to 2.57, p=0.02) women with GDM had greater hypertension risk
      relative to their race/ethnicity-specific counterparts without GDM in race
      stratified multivariable analyses. In conclusion, Hispanic women compared with
      white women have an increased risk of hypertension. Hispanic and white women with
      GDM are at a greater risk for hypertension compared with those without GDM.
      Because the present study may have had limited power to detect effects among
      black and Asian women with GDM, further research is warranted to elucidate the
      need for enhanced hypertension risk surveillance in these young women.

PMID- 24576545
TI  - Left ventricular systolic function following alcohol septal ablation for
      symptomatic hypertrophic cardiomyopathy.
AB  - Because alcohol septal ablation (ASA) for the treatment of symptomatic
      hypertrophic cardiomyopathy (HC) with left ventricular (LV) outflow tract (LVOT)
      obstruction results in a myocardial infarct of up to 10% of ventricular mass, LV
      systolic function could decline over time. We evaluated LV function during
      longitudinal follow-up in a cohort of patients who underwent ASA. We studied 145
      consecutive patients with HC that underwent 167 ASA procedures from 2002 to 2011.
      Echocardiographic follow-up was available in 139 patients (96%).
      Echocardiographic indexes included LV ejection fraction (LVEF), mitral
      regurgitation severity, systolic anterior motion of the anterior mitral leaflet,
      and resting and provoked LVOT gradients. All patients had a baseline LVEF of
      >55%. LVEF was preserved in 97.1% of patients over a mean follow-up time of 3.1+/
      2.3 years (maximum 9.7). Mild LV systolic dysfunction was observed (LVEF range
      44% to 54%) in only 4 patients. Mitral regurgitation severity improved in 67%
      (n=112 of 138 with complete data). Resting LVOT gradient declined from a mean of
      75 to 19 mm Hg (p<0.001), and provoked gradient declined from a mean of 101 to 33
      mm Hg (p<0.001). New York Heart Association class improved from a mean of 2.9+/
      0.4 to 1.3+/-0.5 (p<0.001). In conclusion, LV systolic function is only mildly
      reduced in a minority of patients after ASA for symptomatic HC; other
      echocardiographic and functional measures were significantly improved.

PMID- 24576539
TI  - Establishing the pre-placodal region and breaking it into placodes with distinct
      identities.
AB  - Specialized sensory organs in the vertebrate head originate from thickenings in
      the embryonic ectoderm called cranial sensory placodes. These placodes, as well
      as the neural crest, arise from a zone of ectoderm that borders the neural plate.
      This zone separates into a precursor field for the neural crest that lies
      adjacent to the neural plate, and a precursor field for the placodes, called the
      pre-placodal region (PPR), that lies lateral to the neural crest. The neural
      crest domain and the PPR are established in response to signaling events mediated
      by BMPs, FGFs and Wnts, which differentially activate transcription factors in
      these territories. In the PPR, members of the Six and Eya families, act in part
      to repress neural crest specific transcription factors, thus solidifying a
      placode developmental program. Subsequently, in response to environmental cues
      the PPR is further subdivided into placodal territories with distinct
      characteristics, each expressing a specific repertoire of transcription factors
      that provide the necessary information for their progression to mature sensory
      organs. In this review we summarize recent advances in the characterization of
      the signaling molecules and transcriptional effectors that regulate PPR
      specification and its subdivision into placodal domains with distinct identities.

PMID- 24576546
TI  - Impact of the preoperative risk and the type of surgery on exercise capacity and
      training after valvular surgery.
AB  - Information on exercise capacity and training in patients who underwent valvular
      surgery is scarce. The aim of this study is to evaluate postoperative exercise
      capacity and functional improvement after exercise training according to the
      preoperative risk and type of surgery. In this prospective study, 145 patients
      who underwent aortic valve surgery (AVS) or mitral valve surgery (MVS) and who
      were referred for cardiac rehabilitation were stratified according to the
      preoperative risk (European System for Cardiac Operative Risk Evaluation
      [EuroSCORE]) and type of surgery (sternotomy vs ministernotomy or port access).
      Exercise capacity was evaluated at the start and end of cardiac rehabilitation.
      Postoperative exercise capacity and the benefit from exercise training were
      compared between the groups. Patients with a higher preoperative risk had a worse
      postoperative exercise capacity, with a lower load, peak VO2, anaerobic threshold
      and 6-minute walking distance (all p<0.001), and a higher VE/VCO2 slope (p=0.01).
      In MVS, port access patients performed significantly better at baseline (all
      p<0.05), but in AVS, ministernotomy patients performed better than sternotomy
      patients with a concomitant coronary artery bypass graft (p<0.05). Training
      resulted in an improvement in exercise capacity in each risk group and each type
      of surgery (all p<0.05). This gain in exercise capacity was comparable for the
      EuroSCORE risk groups and for the types of surgery, for patients after AVS or
      MVS. In conclusion, exercise capacity after cardiac surgery is related to the
      preoperative risk and the type of surgery. Despite these differences in
      postoperative exercise capacity, a similar benefit from exercise training is
      obtained, regardless of their preoperative risk or type of surgery.

PMID- 24576547
TI  - Safety of short-term use of dabigatran or rivaroxaban for direct-current
      cardioversion in patients with atrial fibrillation and atrial flutter.
AB  - Direct-current cardioversion (DCCV) for persistent atrial fibrillation or atrial
      flutter (AF) carries a risk of thromboembolic events (TEs). Therapeutic
      anticoagulation with warfarin is recommended for 3 to 4 weeks before and 4 weeks
      after DCCV to reduce TE; however, the safety of short-term anticoagulation with
      the novel oral anticoagulants (dabigatran and rivaroxaban) before DCCV has not
      been assessed. A retrospective cohort study was performed on all patients
      undergoing elective DCCV for AF at Northwestern Memorial Hospital from June 1,
      2012 to September 30, 2013. Inclusion criteria included patients taking any of
      the novel oral anticoagulants for 21 to 60 days before DCCV and successful DCCV
      to sinus rhythm. Patients were monitored for a minimum of 60 days after DCCV to
      evaluate for TEs including stroke, transient ischemic attack, systemic emboli,
      and death. In total, 53 patients (47 men, 89%; age 65+/-10 years, median 66) were
      evaluated. Agents used were dabigatran (30 patients, 57%) and rivaroxaban (23
      patients, 43%) for an average of 38+/-9 days. The mean CHADS2 score was 1.2+/-1.1
      (score=0, 26%; 1, 43%; 2, 17%; and >3, 13%). Eleven patients (21%) underwent a
      transesophageal echocardiography before their DCCV; all showed no thrombus. No
      patients were found to have episodes of TE within 60 days of DCCV. No patients
      were found to have major bleeding events. In conclusion, the use of short-term
      dabigatran or rivaroxaban therapy for DCCV of AF appears safe.

PMID- 24576548
TI  - Relation between topical application of platelet-rich plasma and vancomycin and
      severe deep sternal wound infections after a first median sternotomy.
AB  - Deep sternal wound infections (DSWIs) are serious complications of sternotomy,
      leading to increased mortality and costs of care. Topical applications of
      autologous platelet concentrate and vancomycin have both shown promise in
      preventing DSWIs. From January 1, 1998, to November 30, 2010, 1,866 patients
      without previous sternotomy underwent cardiac surgery at the Baylor University
      Medical Center, Dallas, by a single surgeon who systematically adopted
      application of a paste containing vancomycin, calcium-thrombin, and platelet-rich
      plasma (PRP paste) to the edges of sternal wounds before closure in December
      2005. A propensity-adjusted logistic regression model employing Firth's penalized
      maximum likelihood method was used to assess the association between the use of
      the PRP paste (intervention) and the incidence of severe DSWI. Eleven patients
      (0.59%) developed severe DSWIs. All were among the 1,318 patients in the control
      group (0.83%); no severe DSWIs developed in the 548 patients in the intervention
      group. Both the unadjusted and adjusted associations between the study
      intervention and DSWI were statistically significant (unadjusted p value=0.021;
      adjusted p value=0.005; adjusted odds ratio=0.05, 95% confidence interval 0.01,
      0.50). In conclusion, the PRP paste appears to prevent severe DSWIs.

PMID- 24576549
TI  - Nursing must be a graduate profession (Well, he would say that, wouldn't he!).

PMID- 24576550
TI  - The eIF2B-interacting domain of RGS2 protects against GPCR agonist-induced
      hypertrophy in neonatal rat cardiomyocytes.
AB  - The protective effect of Regulator of G protein Signaling 2 (RGS2) in cardiac
      hypertrophy is thought to occur through its ability to inhibit the chronic GPCR
      signaling that promotes pathogenic growth both in vivo and in cultured
      cardiomyocytes. However, RGS2 is known to have additional functions beyond its
      activity as a GTPase accelerating protein, such as the ability to bind to
      eukaryotic initiation factor, eIF2B, and inhibit protein synthesis. The RGS2
      eIF2B-interacting domain (RGS2(eb)) was examined for its ability to regulate
      hypertrophy in neonatal ventricular myocytes. Both full-length RGS2 and RGS2(eb)
      were able to inhibit agonist-induced cardiomyocyte hypertrophy, but RGS2(eb) had
      no effect on receptor-mediated inositol phosphate production, cAMP production, or
      ERK 1/2 activation. These results suggest that the protective effects of RGS2 in
      cardiac hypertrophy may derive at least in part from its ability to govern
      protein synthesis. 

PMID- 24576551
TI  - Differential effects of genetically-encoded Gbetagamma scavengers on receptor
      activated and basal Kir3.1/Kir3.4 channel current in rat atrial myocytes.
AB  - Opening of G-protein-activated inward-rectifying K(+) (GIRK, Kir3) channels is
      regulated by interaction with betagamma-subunits of Pertussis-toxin-sensitive G
      proteins upon activation of appropriate GPCRs. In atrial and neuronal cells
      agonist-independent activity (I(basal)) contributes to the background K(+)
      conductance, important for stabilizing resting potential. Data obtained from the
      Kir3 signaling pathway reconstituted in Xenopus oocytes suggest that I(basal)
      requires free G(betagamma). In cells with intrinsic expression of Kir3 channels
      this issue has been scarcely addressed experimentally. Two G(betagamma)-binding
      proteins (myristoylated phosducin - mPhos - and G(alphai1)) were expressed in
      atrial myocytes using adenoviral gene transfer, to interrupt G(betagamma)
      signaling. Agonist-induced and basal currents were recorded using whole cell
      voltage-clamp. Expression of mPhos and G(alphai1) reduced activation of Kir3
      current via muscarinic M(2) receptors (IK(ACh)). Inhibition of IK(ACh) by mPhos
      consisted of an irreversible component and an agonist-dependent reversible
      component. Reduction in density of IK(ACh) by overexpressed Galphai1, in contrast
      to mPhos, was paralleled by substantial slowing of activation, suggesting a
      reduction in density of functional M2 receptors, rather than G(betagamma)
      scavenging as underlying mechanism. In line with this notion, current density and
      activation kinetics were rescued by fusing the alphai1-subunit to an Adenosine
      A(1) receptor. Neither mPhos nor G(alphai1) had a significant effect on I(basal),
      defined by the inhibitory peptide tertiapin-Q. These data demonstrate that basal
      Kir3 current in a native environment is unrelated to G-protein signaling or
      agonist-independent free G(betagamma). Moreover, our results illustrate the
      importance of physiological expression levels of the signaling components in
      shaping key parameters of the response to an agonist.

PMID- 24576552
TI  - Subchronic toxicity study of beta-hydroxy-beta-methylbutyric free acid in Sprague
      Dawley rats.
AB  - Calcium beta-hydroxy-beta-methylbutyrate-monohydrate (CaHMB) is a dietary
      supplement used as an ergogenic aid and in functional and medical foods. A new
      delivery form has been developed, beta-hydroxy-beta-methylbutyric free acid
      (HMBFA), which has improved bioavailability. While the safety of CaHMB is well
      documented, there are few published studies demonstrating the safety of HMBFA.
      Because HMBFA results in greater serum levels of beta-hydroxy-beta-methylbutyrate
      (HMB) and greater clearance rates, a 91-day subchronic toxicity study was
      conducted in male and female Sprague-Dawley Crl:CD rats assigned to HMBFA
      treatments at either 0%, 0.8%, 1.6%, or 4% of the diet by weight. No deaths or
      untoward clinical observations, and no negative clinical chemistry or hematology
      were attributed to the administration of HMBFA. Gross pathology and
      histopathology results showed no tissue abnormalities due to HMBFA and all
      measures were within a normal physiological range for the animals or were
      expected in the population studied. In conclusion, the no-observed-adverse-event
      level (NOAEL) for HMBFA was the highest level administered, 4% of the diet, which
      corresponded to an intake of 2.48 and 2.83 g/kg BW d(-1) in the males and
      females, respectively. The equivalent human dosage using body surface area
      conversion would be 402 and 459 mg/kg BW d(-1) for men and women, respectively.

PMID- 24576553
TI  - Real-time investigation of a Legionella pneumophila outbreak using whole genome
      sequencing.
AB  - Legionella pneumophila is the main pathogen responsible for outbreaks of
      Legionnaires' disease, which can be related to contaminated water supplies such
      as cooling towers or water pipes. We combined conventional molecular methods and
      whole genome sequence (WGS) analysis to investigate an outbreak of L. pneumophila
      in a large Australian hospital. Typing of these isolates using sequence-based
      typing and virulence gene profiling, was unable to discriminate between outbreak
      and non-outbreak isolates. WGS analysis was performed on isolates during the
      outbreak, as well as on unlinked isolates from the Public Health Microbiology
      reference collection. The more powerful resolution provided by analysis of whole
      genome sequences allowed outbreak isolates to be distinguished from isolates that
      were temporally and spatially unassociated with the outbreak, demonstrating that
      this technology can be used in real-time to investigate L. pneumophila outbreaks.

PMID- 24576554
TI  - Dynamics and reproductive effects of complement factors in the spontaneous
      abortion model of CBA/J*DBA/2 mice.
AB  - The complement system is one component of innate immunity that could participate
      in fetal loss. We have already reported that adipsin, a complement activator in
      the alternative pathway, is stably expressed in the placenta and that an increase
      in this expression is related to spontaneous abortion. However, complement
      inhibitor Crry was concurrently expressed in the placenta, and the role of
      complement factors during pregnancy was not clear. In the present study, we
      examined the endogenous regulation of complement factors in placenta and serum by
      using another model mouse for spontaneous abortion and studied the effect of
      exogenous complement disruption on pregnancy. Compared to control mice, the
      CBA/J*DBA/2 model mice had higher expression levels of adipsin in the placenta
      and serum. Adipsin and complement C3 were localized in the metrial gland and
      labyrinth regions, and both positive reactive ranges were limited in the maternal
      blood current in normal implantation sites. These results suggest that
      extrauterine adipsin hematogenously reaches the placenta, activates complement
      C3, and promotes destruction of the feto-maternal barrier in aborted implantation
      sites. Crry was consistently expressed in the placenta and serum and reduced in
      the resorption sites of CBA/J*DBA/2 mice as compared to normal sites. Injection
      of recombinant adipsin increased the resorption rate and changed the expression
      of Th-type cytokines toward a Th1 bias. The present study indicates that adipsin
      could induce the fetal loss that accompanies the Th1 bias and may be a crucial
      cause of spontaneous abortion. In addition, the local expression of Crry prevents
      complement activation in placenta in response to a systemic increase of adipsin. 

PMID- 24576555
TI  - Protocatechuic acid inhibits human dendritic cell functional activation: role of
      PPARgamma up-modulation.
AB  - Polyphenols have been shown to exhibit anti-inflammatory, anti-oxidant and
      immunomodulatory activities. However, the effects of anthocyanins, flavonoids of
      great nutritional interest, in particular of their metabolite protocatechuic acid
      (PCA) on the phenotypic and functional maturation of human dendritic cells (DCs)
      are still largely unknown. In this study, we report that PCA is efficiently taken
      up and accumulated in human monocyte-derived DCs (MD-DCs). PCA exposure of MD-DCs
      markedly impaired the production of proinflammatory cytokines and chemokines
      (i.e. IL-6, IL-8 and CCL2) in response to bacterial endotoxin and leptin, and
      down-regulated the lipopolysaccharide (LPS)-induced migratory response of MD-DCs
      to CCL19. Conversely, the phenotypic profile induced by LPS-mediated activation
      as well as IL-12 production was not affected. Interestingly, we found that
      PPARgamma is a main factor in the PCA-induced effects as blocking its activity
      abolish PCA capacity to down-regulate IL-6 and IL-8, but not CCL2, secretion and
      to inhibit MD-DC migration. In keeping with this observation, cytosol to nucleus
      translocation and PPARgamma activity were found to be directly stimulated by PCA
      exposure of MD-DCs. These novel findings provide new insight into the
      immunoregulatory effects of polyphenol metabolites in DCs opening new
      perspectives on their potential application in the prevention of acute and
      chronic inflammatory diseases. 

PMID- 24576558
TI  - The single nucleotide polymorphisms in Smad-interacting protein 1 gene contribute
      to its ectopic expression and susceptibility in Hirschsprung's disease.
AB  - Hirschsprung's disease (HSCR) is the third most common congenital disorder of the
      gastrointestinal tract. It is an anomalous enteric nervous system (ENS)
      characterized by the absence of ganglion cells in the myenteric and submucosal
      plexuses. It has been reported that the Smad-interacting protein 1(SIP1) is
      critical in embryonic development of ENS for its regulation on neural crest
      cells. In the present study, we analyzed 3 polymorphisms of the SIP1 gene
      rs41292293 (exon5), rs34961586 (exon6) and rs13017697 (exon8) to determine their
      potential contributions to the susceptibility of HSCR. Allele frequencies and
      genotype distributions were analyzed by sequence analysis in 107 HSCR patients
      and 107 normal controls. The SIP1 expression was carried out by using real-time
      PCR, western blot and immunohistochemistry. Polymorphic analysis indicated that
      the genotype distributions and allele frequencies in SIP1 gene rs41292293,
      rs34961586 and rs13017697 were statistically different between HSCR and normal
      controls. The expression analysis revealed that SIP1 was ectopically expressed in
      the aganglionic segments; neither the mRNA nor the protein levels demonstrated
      that the difference compared with those was in the normal segments. In
      conclusion, the single nucleotide polymorphisms in SIP1 gene rs41292293,
      rs34961586 and rs13017697 are associated with the ectopic expression of this gene
      in human HSCR and contribute to the susceptibility of this disease in population.

PMID- 24576557
TI  - Mitochondrial membrane assembly of TMEM70 protein.
AB  - Dysfunction of TMEM70 disrupts the biogenesis of ATP synthase and represents the
      frequent cause of autosomal recessive encephalocardiomyopathy. We used tagged
      forms of TMEM70 and demonstrated that it has a hairpin structure with the N- and
      C-termini oriented towards the mitochondrial matrix. On BN-PAGE TMEM70 was
      detected in multiple forms including dimers and displayed partial overlap with
      assembled ATP synthase. Immunoprecipitation studies confirmed mutual interactions
      between TMEM70 molecules but, together with immunogold electron microscopy, not
      direct interaction with ATP synthase subunits. This indicates that the biological
      function of TMEM70 in the ATP synthase biogenesis may be mediated through
      interaction with other protein(s). 

PMID- 24576559
TI  - Importance of reduced sulfur for the equilibrium chemistry and kinetics of
      Fe(II), Co(II) and Ni(II) supplemented to semi-continuous stirred tank biogas
      reactors fed with stillage.
AB  - The objective of the present study was to assess major chemical reactions and
      chemical forms contributing to solubility and speciation of Fe(II), Co(II), and
      Ni(II) during anaerobic digestion of sulfur (S)-rich stillage in semi-continuous
      stirred tank biogas reactors (SCSTR). These metals are essential supplements for
      efficient and stable performance of stillage-fed SCSTR. In particular, the
      influence of reduced inorganic and organic S species on kinetics and
      thermodynamics of the metals and their partitioning between aqueous and solid
      phases were investigated. Solid phase S speciation was determined by use of S K
      edge X-ray absorption near-edge spectroscopy. Results demonstrated that the
      solubility and speciation of supplemented Fe were controlled by precipitation of
      FeS(s) and formation of the aqueous complexes of Fe-sulfide and Fe-thiol. The
      relatively high solubility of Co (~ 20% of total Co content) was attributed to
      the formation of compounds other than Co-sulfide and Co-thiol, presumably of
      microbial origin. Nickel had lower solubility than Co and its speciation was
      regulated by interactions with FeS(s) (e.g. co-precipitation, adsorption, and ion
      substitution) in addition to precipitation/dissolution of discrete NiS(s) phase
      and formation of aqueous Ni-sulfide complexes.

PMID- 24576560
TI  - Role of epidermal stem cells in repair of partial-thickness burn injury after
      using Moist Exposed Burn Ointment (MEBO((r))) histological and
      immunohistochemical study.
AB  - Moist Exposed Burn Ointment (MEBO((r))) is widely used topical agent applied on
      skin burn. This study investigated the effect of MEBO topical application on
      activation and proliferation of epidermal stem cells through the
      immunohistochemical localization of cytokeratin 19 (CK19) as a known marker
      expressed in epidermal stem cells. Biopsies from normal skin and burn wounds were
      taken from 21 patients with partial thickness burn 1, 4, 7, 14, 21, and 28 days
      after treatment with MEBO. Tissue sections were prepared for histological study
      and for CK19 immunohistochemical localization. In control skin, only few cells
      showed a positive CK19 immune-reaction. Burned skin showed necrosis of full
      thickness epidermis that extended to dermis. Gradual regeneration of skin
      accompanied with an enhancement in CK19 immune-reactivity was noted 4, 7, 14 and
      21 days after treatment with MEBO. On day 28, a complete regeneration of skin was
      observed with a return of CK19 immune-reactivity to the basal pattern again. In
      conclusion, the enhancement of epidermal stem cell marker CK19 after treatment of
      partial thickness burn injuries with MEBO suggested the role of MEBO in promoting
      epidermal stem cell activation and proliferation during burn wound healing.

PMID- 24576561
TI  - Ubiquinol-10 ameliorates mitochondrial encephalopathy associated with CoQ
      deficiency.
AB  - Coenzyme Q10 (CoQ10) deficiency (MIM 607426) causes a mitochondrial syndrome with
      variability in the clinical presentations. Patients with CoQ10 deficiency show
      inconsistent responses to oral ubiquinone-10 supplementation, with the highest
      percentage of unsuccessful results in patients with neurological symptoms
      (encephalopathy, cerebellar ataxia or multisystemic disease). Failure in the
      ubiquinone-10 treatment may be the result of its poor absorption and
      bioavailability, which may be improved by using different pharmacological
      formulations. In a mouse model (Coq9(X/X)) of mitochondrial encephalopathy due to
      CoQ deficiency, we have evaluated oral supplementation with water-soluble
      formulations of reduced (ubiquinol-10) and oxidized (ubiquinone-10) forms of
      CoQ10. Our results show that CoQ10 was increased in all tissues after
      supplementation with ubiquinone-10 or ubiquinol-10, with the tissue levels of
      CoQ10 with ubiquinol-10 being higher than with ubiquinone-10. Moreover, only
      ubiquinol-10 was able to increase the levels of CoQ10 in mitochondria from
      cerebrum of Coq9(X/X) mice. Consequently, ubiquinol-10 was more efficient than
      ubiquinone-10 in increasing the animal body weight and CoQ-dependent respiratory
      chain complex activities, and reducing the vacuolization, astrogliosis and
      oxidative damage in diencephalon, septum-striatum and, to a lesser extent, in
      brainstem. These results suggest that water-soluble formulations of ubiquinol-10
      may improve the efficacy of CoQ10 therapy in primary and secondary CoQ10
      deficiencies, other mitochondrial diseases and neurodegenerative diseases. 

PMID- 24576563
TI  - Implementing psychological first-aid training for medical reserve corps
      volunteers.
AB  - OBJECTIVE: We assessed the feasibility and impact on knowledge, attitudes, and
      reported practices of psychological first-aid (PFA) training in a sample of
      Medical Reserve Corps (MRC) members. Data have been limited on the uptake of PFA
      training in surge responders (eg, MRC) who are critical to community response.
      METHODS: Our mixed-methods approach involved self-administered pre- and post
      training surveys and within-training focus group discussions of 76 MRC members
      attending a PFA training and train-the-trainer workshop. Listen, protect, connect
      (a PFA model for lay persons) focuses on listening and understanding both verbal
      and nonverbal cues; protecting the individual by determining realistic ways to
      help while providing reassurance; and connecting the individual with resources in
      the community. RESULTS: From pre- to post-training, perceived confidence and
      capability in using PFA after an emergency or disaster increased from 71% to 90%
      (P < .01), but no significant increase was found in PFA-related knowledge.
      Qualitative analyses suggest that knowledge and intentions to use PFA increased
      with training. Brief training was feasible, and while results were modest, the
      PFA training resulted in greater reported confidence and perceived capability in
      addressing psychological distress of persons affected by public health threats.
      CONCLUSION: PFA training is a promising approach to improve surge responder
      confidence and competency in addressing postdisaster needs.

PMID- 24576562
TI  - Outbreak of type A foodborne botulism at a boarding school, Uganda, 2008.
AB  - Botulism has rarely been reported in Africa. In October 2008, botulism was
      reported in three Ugandan boarding-school students. All were hospitalized and one
      died. A cohort study was performed to assess food exposures among students, and
      clinical specimens and available food samples were tested for botulinum toxin.
      Three case-patients were identified; a homemade, oil-based condiment was eaten by
      all three. In the cohort study, no foods were significantly associated with
      illness. Botulinum toxin type A was confirmed in clinical samples. This is the
      first confirmed outbreak of foodborne botulism in Uganda. A homemade, oil-based
      condiment was the probable source. Consumption of homemade oil-based condiments
      is widespread in Ugandan schools, putting children at risk. Clinicians and public
      health authorities in Uganda should consider botulism when clusters of acute
      flaccid paralysis are seen. Additionally, schools should be warned of the hazard
      of homemade oil-based condiments, and take steps to prevent their use.

PMID- 24576564
TI  - [Post-traumatic retinal detachment with posterior giant retinal tear].

PMID- 24576565
TI  - [Acquired trichomegaly and hypertrichosis].

PMID- 24576566
TI  - [Birth-related retinal hemorrhages in the newborn: incidence and relationship
      with maternal, obstetric and neonatal factors. Prospective study of 2,031 cases].
AB  - PURPOSE: To assess the prevalence, morphology and distribution of retinal
      hemorrhages in healthy newborns and their relationship to neonatal, maternal and
      obstetrical factors, and to determine their natural history. PATIENTS AND
      METHODS: The present study prospectively included 2,031 consecutive healthy
      newborns. Indirect ophthalmoscopy was performed within 24 hours after birth in
      all newborns. Infants with retinal hemorrhages were reexamined weekly until the
      hemorrhage resolved. Annual ophthalmologic follow-up was also scheduled in these
      children. Neonatal, maternal and obstetric parameters were analyzed in all
      newborns and compared between newborns with retinal hemorrhages and those without
      retinal hemorrhages. RESULTS: 31.8 % of newborns exhibited retinal hemorrhages.
      72.6 % of hemorrhages were bilateral. They tended to be localized around the
      optic discs and in the posterior pole, but their distribution was variable.
      Retinal hemorrhages were of variable shapes. The prevalence of retinal
      hemorrhages was higher in newborns delivered with vacuum-assisted extraction (38
      %, P<0.001), intermediate during normal vaginal delivery (32.6 %, P<0.001) and
      lower with cesarean section (20.8 %). Comparative analysis between elective
      cesarean section and emergency cesarean showed a higher incidence of retinal
      hemorrhages in the emergency cesarean group (P=0.006). On multivariate analysis,
      vacuum-assisted delivery was the only factor associated with a higher prevalence
      of retinal hemorrhages in newborns (P=0.045). Two thirds of hemorrhages had
      disappeared by one week after birth. Retinal hemorrhages had resolved in all
      newborns within four weeks. CONCLUSION: Birth-related retinal hemorrhages are
      common (1/3 of our newborns). Vacuum-assisted delivery is the main risk factor in
      this study. All hemorrhages resolved by one month of age. These findings may help
      in differential diagnosis with shaken baby syndrome.

PMID- 24576567
TI  - [Post-vitrectomy maculopathy, or "why doesn't my retinal detachment patient see
      better?"].
AB  - Retinal detachment (RD) is a surgical disease with good anatomical results thanks
      to advances in vitreo-retinal surgical techniques. However, in spite of good
      anatomical results, visual recovery may sometimes be clearly less satisfactory.
      These poor functional results may be due to epiretinal membranes, macular holes
      or macula edema, some of which may be transitory, and some of which may be
      amenable to surgical treatment. However, some circumstances can be explained only
      by an alteration of deep retinal layers, especially at the photoreceptor level.
      Newer OCTs (optical coherence tomography) can provide a more detailed in vivo
      anatomical assessment of the retina, to which microperimetry can add a functional
      perspective. Better understanding of poor prognostic factors (poor preoperative
      visual acuity, RD duration, height of the macular detachment) can improve the
      quality of information given to the patient.

PMID- 24576569
TI  - Two cases of bilateral amiodarone-associated optic neuropathy.
AB  - INTRODUCTION: The widespread use of amiodarone is limited by its toxicity,
      notably to the optic nerve. We report two cases of bilateral optic nerve
      neuropathy due to amiodarone, and provide a detailed description of the disease.
      OBSERVATIONS: The first case was a 59-year-old man complaining from insidious
      monocular loss of vision within ten months of initiating amiodarone. Funduscopy
      and optical coherence tomography showed bilateral optic disc edema. The second
      case was a 72-year-old man presenting with a decrease in visual acuity in his
      left eye for a month. Funduscopy showed a left optic nerve edema, and fluorescein
      angiography showed bilateral papillitis. In both cases, the clinical presentation
      was not suggestive of ischemic neuropathy, because of the preservation of visual
      acuity and the insidious onset. In addition, both cardiovascular and inflammatory
      work-up were normal. An amiodarone-associated neuropathy was suspected, and
      amiodarone was discontinued with the approval of the cardiologist, with complete
      regression of the papilledema and a stabilization of visual symptoms. DISCUSSION:
      Differentiating between amiodarone-associated optic neuropathy and anterior
      ischemic optic neuropathy may be complicated by the cardiovascular background of
      such patients. The major criterion is the absence of a severe decrease in visual
      acuity; other criteria are the normality of cardiovascular and inflammatory work
      up, and the improvement or the absence of worsening of symptoms after
      discontinuation of amiodarone. CONCLUSION: Amiodarone-associated neuropathy
      remains a diagnosis of exclusion, and requires amiodarone discontinuation, which
      can only be done with the approval of a cardiologist, and sometimes requires
      replacement therapy.

PMID- 24576570
TI  - [Endo-dacryocystorhinostomy, middle turbinate and uncinate process].

PMID- 24576568
TI  - [Battery of rockets "Scedosporium Apiospermum" in mycotic keratitis].

PMID- 24576571
TI  - Using flow cytometry to detect haemic neoplasia in mussels (Mytilus trossulus)
      from the Pacific Coast of Southern British Columbia, Canada.
AB  - Flow cytometry was investigated as an alternative to visual haemocytology for
      potentially higher-throughput and less subjective detection of neoplasia in
      Mytilus trossulus. In contrast to previous studies of ploidy in the Mytilus spp.
      complex, distinct tetra- and pentaploidal neoplastic cells were rare and a wide
      range of aneuploidy peaks from 1.4n to 5.5n were detected for late-stage leukemic
      animals. There was no correlation between aneuploidy and the number of diseased
      cells for early and intermediate disease stages. Formation of aneuploidy and
      neoplasia progression might not be simultaneous, and DNA content analysis using
      flow cytometry was only useful for detecting late stages of the disease. 

PMID- 24576572
TI  - Toxicological evaluation of 6:2 fluorotelomer alcohol.
AB  - 6:2 fluorotelomer alcohol (6:2 FTOH; CF3[CF2]5[CH2]2OH, CAS# 647-42-7) was
      evaluated for acute, genetic, and subchronic toxicity using in vitro and in vivo
      methods. In rats, 6:2 FTOH was considered to be slightly toxic by the oral
      (LD50=1,750 mg/kg), and dermal (LD50 > 5,000 mg/kg) routes. In rabbits, 6:2 FTOH
      was not a primary skin or eye irritant, and it did not produce a dermal
      sensitization response in mice. In a 90-day subchronic study, 6:2 FTOH was
      administered to rats by oral gavage (0, 5, 25, 125, 250 mg/kg/day). Mortality was
      observed at 125 and 250 mg/kg/day; deaths occurred after approximately three
      weeks of dosing and continued sporadically. The NOAEL in the subchronic study was
      5mg/kg/day based on hematology and liver effects. 6:2 FTOH was not mutagenic in
      the bacterial reverse mutation test or in the mouse lymphoma assay and was not
      clastogenic in a chromosome aberration assay in human lymphocytes. The hazard
      classification for human health endpoints of 6:2 FTOH according to the United
      Nations Globally Harmonized System of Classification and Labeling of Chemicals
      (GHS) is Category 4 for acute oral toxicity based on an LD50 of 1,750 mg/kg.
      Other acute health endpoints including eye and skin irritation, skin
      sensitization, as well as genotoxicity, did not meet the criteria for hazard
      classification. Benchmark Dose Analysis was performed on the most sensitive
      endpoints from the 90-day oral gavage study and these levels were all above the
      study NOAEL of 5mg/kg/day. For risk assessment purposes, the recommended point of
      departure is the more conservative study NOAEL of 5mg/kg/day.

PMID- 24576573
TI  - Psychiatric symptoms are not an independent mortality risk factor in community
      living elderly people.
AB  - BACKGROUND: Mortality risk factors have attracted great research interest in
      recent years. Physical illness is strongly associated with mortality risk in
      elderly people. Furthermore, a relationship between mortality risk and
      psychiatric disease in the elderly has gained research interest. METHODS: This is
      a prospective longitudinal multicenter study. A sample of 324 participants was
      selected as a representative sample of community members aged 65 years and older
      and living in Huesca (Spain). The following information was collected:
      affiliation data, severity of physical illness, psychosocial, and psychiatric
      factors. Statistical analyses were completed with a multivariate analysis in
      order to control possible confounding variables related to mortality. RESULTS: Of
      the initially selected sample, 293 participants were assessed. Sixty-four
      participants died (21.8%, 95% CI [16.9%, 26.7%]), 5.3% annual rate, and 46.1%
      showed symptomatology of mental disorders. Older people have eight times greater
      risk of mortality. The risk increased 53 times in patients affected by several
      physical illness. No relationship between cognitive dysfunction and depressive
      symptomatology was observed. In fact, physical condition was associated with
      depression, and the percentage of participants with depressive symptoms increased
      according to the severity of physical illness. CONCLUSIONS: Severity of physical
      illness and age are independently and directly associated with mortality in the
      elderly people. Therefore, severity of physical illness seems to be a crucial
      factor in the bi-directional association between mortality and depression, acting
      as a risk factor independently for both. So the relationship between depression
      and mortality can be affected by the severity of physical illness.

PMID- 24576575
TI  - Influence of tris(2,3-dibromopropyl) isocyanurate on the expression of
      photosynthesis genes of Nannochloropsis sp.
AB  - The proteins encoded by psaA and psaB form a heterodimer, an essential compound
      of photosystem; while the protein encoded by psbC binds with chlorophyll a in
      photosystem II, serving as antennae in photosystem. Here we report that a
      heterocyclic brominated flame retardant, tris(2,3-dibromopropyl) isocyanurate
      (TBC), inhibited the expression of psaA and psbC, then leads to the decrease of
      Nannochloropsis sp.'s growth biomass. TBC exposure inhibited the expression of
      psaA and psbC at 10, 100ng/mL slightly and 1000ng/mL significantly. In addition,
      TBC was found to slow down the growth of Nannochloropsis sp. at concentrations
      ranging from 10 to 1000ng/mL. These results indicated that TBC influenced both
      photosynthesis and growth performance of Nannochloropsis sp. 

PMID- 24576577
TI  - The oncoprotein v-Myb activates transcription of Gremlin 2 during in vitro
      differentiation of the chicken neural crest to melanoblasts.
AB  - The neural crest (NC) is a transient dynamic structure of ectodermal origin,
      found in early vertebrate embryos. The multipotential NC cells migrate along well
      defined routes, differentiate to various cell types including melanocytes and
      participate in the formation of various permanent tissues. As there is only
      limited information about the molecular mechanisms controlling early events in
      melanocyte specification and development, we exploited the AMV v-Myb
      transcriptional regulator, which directs differentiation of in vitro chicken NC
      cells to the melanocyte lineage. This activity is strictly dependent on v-Myb
      specifically binding to the Myb recognition DNA element (MRE). The two tamoxifen
      inducible v-Myb alleles were constructed one which recognizes the MRE and one
      which does not. These were activated in ex ovo NC cells, and the expression
      profiles of resulting cells were analyzed using Affymetrix microarrays and RT
      PCR. These approaches revealed up-regulation of the BMP antagonist Gremlin 2
      mRNA, and down-regulation of mRNAs encoding several epithelial genes including
      KRT19 as very early events following the activation of melanocyte differentiation
      by v-Myb. The enforced v-Myb expression in neural tubes of chicken embryos
      resulted in detectable presence of Gremlin 2 mRNA. However, expression of Gremlin
      2 in NC cells did not promote formation of melanocytes suggesting that Gremlin 2
      is not the master regulator of melanocytic differentiation. 

PMID- 24576574
TI  - Disulfide bond formation in prokaryotes: history, diversity and design.
AB  - The formation of structural disulfide bonds is essential for the function and
      stability of a great number of proteins, particularly those that are secreted.
      There exists a variety of dedicated cellular catalysts and pathways from archaea
      to humans that ensure the formation of native disulfide bonds. In this review we
      describe the initial discoveries of these pathways and report progress in recent
      years in our understanding of the diversity of these pathways in prokaryotes,
      including those newly discovered in some archaea. We will also discuss the
      various successful efforts to achieve laboratory-based evolution and design of
      synthetic disulfide bond formation machineries in the bacterium Escherichia coli.
      These latter studies have also led to new more general insights into the redox
      environment of the cytoplasm and bacterial cell envelope. This article is part of
      a Special Issue entitled: Thiol-Based Redox Processes. 

PMID- 24576578
TI  - Applications of a 7-day Caco-2 cell model in drug discovery and development.
AB  - Oral delivery is the preferred route of administration and therefore good
      absorption after oral dosing is a prerequisite for a compound to be successful in
      the clinic. The prediction of oral bioavailability from in vitro permeability
      assays is thus a valuable tool during drug discovery and development. Caco-2 cell
      monolayers mimic the human intestinal epithelium in many aspects. These
      monolayers form tight junctions between cells and have been widely used as a
      model of human intestinal absorption. Caco-2 cells also express a variety of
      transporter proteins although the transformed nature of the cells results in
      unpredictable differentiation markers, transport properties and enzyme
      expression. Thus various modifications of the Caco-2 assay are used in
      laboratories across the globe. The purpose of this paper is to provide an
      overview of a time and resource saving 7-day Caco-2 assay protocol. We also
      discuss the impact of various experimental conditions on permeability
      measurements and its applications during lead optimization in early discovery and
      for clinical candidate characterization, specifically for prediction of
      absorption in human, at a later stage in drug development. 

PMID- 24576576
TI  - Rem2 in the bullfrog (Rana catesbeiana): Patterns of expression within the
      central nervous system and brain expression at different ontogenetic stages.
AB  - Rem2 is a member of the RGK (Rem, Rad, and Gem/Kir) subfamily of the Ras
      superfamily of GTP binding proteins. In mammals, Rem2 has been found to be unique
      in not only its structure, but also its tissue specificity, as it is the first
      member to be found at high levels in neuronal tissue. Because Rem2 has previously
      been implicated in neuronal cell proliferation, and amphibians maintain
      relatively high neuronal proliferative activity as adults, we sought to isolate
      and acquire the full-length sequence of the rem2 gene from the brain of the
      bullfrog (Rana catesbeiana). Furthermore, we used real time PCR (rtPCR) to
      characterize its tissue specificity, regional brain expression, and brain
      expression levels at different stages of development. Deduced amino acid sequence
      analysis showed that the bullfrog Rem2 protein possesses the unique 5' extension
      characteristic of mammalian Rem2 and the RGK subfamily to which it belongs.
      Tissue specificity of the bullfrog rem2 gene showed that the bullfrog is similar
      to both mammals and fish in that the levels of rem2 gene expression were
      significantly greater in the brain than all other tissues assayed. In the brain
      itself, differential rem2 expression patterns were observed between six major
      brain areas assayed and the spinal cord, with expression significantly high in
      the cerebrum and low in the cerebellum. Finally, examination of whole brain rem2
      expression levels in bullfrogs at different stages of development revealed
      greater expression after metamorphic climax. 

PMID- 24576580
TI  - Stem cell-loaded nanofibrous patch promotes the regeneration of infarcted
      myocardium with functional improvement in rat model.
AB  - Myocardial infarction (MI) leads to the loss of cardiomyocytes, followed by left
      ventricular (LV) remodeling and cardiac dysfunction. The authors hypothesize that
      an elastic, biodegradable nanofibrous cardiac patch loaded with mesenchymal stem
      cells (MSC) could restrain LV remodeling and improve cardiac function after MI.
      Poly(epsilon-caprolactone)/gelatin (PG) nanofibers were fabricated by
      electrospinning, and the nanofibers displayed a porous and uniform nanofibrous
      structure with a diameter of 244+/-51nm. An MI model was established by ligation
      of the left anterior descending coronary artery of female Sprague-Dawley rats.
      The PG nanofibrous patch seeded with MSC, isolated from rat bone marrow, was
      implanted on the epicardium of the infarcted region of the LV wall of the heart.
      After transplantation, the PG-cell patch restricted the expansion of the LV wall
      effectively and reduced the scar size, and the density of the microvessels
      increased. Cells within the patch were able to migrate towards the scar tissue,
      and promoted new blood vessel formation at the infarct site. Angiogenesis and the
      cardiac functions improved significantly after 4weeks of implantation. The MSC
      seeded PG nanofibrous patches are demonstrated to provide sufficient mechanical
      support, to induce angiogenesis and to accelerate cardiac repair in a rat model
      of MI. The study highlights the positive impact of implantation of an MSC-seeded
      PG nanofibrous patch as a novel constituent for MI repair.

PMID- 24576579
TI  - Improving the performance of poly(3,4-ethylenedioxythiophene) for brain-machine
      interface applications.
AB  - Conducting polymers, especially poly(3,4-ethylenedioxythiophene) (PEDOT) based
      materials, are important for developing highly sensitive and microscale neural
      probes. In the present work, we show that the conductivity and stability of PEDOT
      can be significantly increased by switching the widely used counter anion
      poly(styrenesulfonate) (PSS) to the smaller tetrafluoroborate (TFB) anion during
      the electrodeposition of the polymer. Time-dependent impedance measurements of
      polymer modified implantable microwires were conducted in physiological buffer
      solutions under accelerated aging conditions and the relative stability of
      PEDOT:PSS and PEDOT:TFB modified microwires was compared over time. This study
      was also extended to carbon nanotube (CNT) incorporated PEDOT:PSS which,
      according to some reports, is claimed to enhance the stability and electrical
      performance of the polymer. However, no noticeable difference was observed
      between PEDOT:PSS and CNT:PEDOT:PSS in our measurements. At the biologically
      relevant frequency of 1kHz, PEDOT:TFB modified microwires exhibit approximately
      one order of magnitude higher conductivity and demonstrate enhanced stability
      over both PEDOT:PSS and CNT:PEDOT:PSS modified microwires. In addition, PEDOT:TFB
      is not neurotoxic and we show the proof-of-concept for both in vitro and in vivo
      neuronal recordings using PEDOT:TFB modified microelectrode arrays and chronic
      electrodes, respectively. Our findings suggest that PEDOT:TFB is a promising
      conductive polymer coating for the recording of neural activities.

PMID- 24576581
TI  - Odontogenic differentiation and dentin formation of dental pulp cells under
      nanobioactive glass induction.
AB  - Bioactive glass (BG) has been widely used in bone regeneration; however, reports
      on the biological effects of BG on dental pulp cells are rare. This study aims to
      investigate the effects of nanoscale BG (n-BG) on odontogenic differentiation and
      dentin formation of dental pulp cells and to compare these effects with those of
      microscale BG (m-BG). Human dental pulp cells (hDPCs) from third molars were
      cultured directly with m-BG and n-BG in vitro. The cell proliferation increased
      at 0.1mgml(-1) BG, which also had a chemotactic effect on hDPCs. The
      mineralization capacity and expression of odontogenic-related proteins and genes
      (dentin sialophosphoprotein, dentin matrix protein 1 and collagen type I) of
      hDPCs were significantly up-regulated under BG induction, and were particularly
      higher in the n-BG group than in the control group. m-BG and n-BG combined with
      pulp tissues were transplanted into the dorsum of immunodeficient mice to observe
      their biological effects on dental pulp cells in vivo. A continuous layer of
      dentin-like tissue with uniform thickness, a well-organized dentinal tubule
      structure and polarizing odontoblast-like cells aligned along it was generated
      upon the n-BG layer, whereas some irregular sporadic osteodentin-like mineralized
      tissues were observed in the control group. This study reveals that BG,
      especially n-BG, induces the odontogenic differentiation and dentin formation of
      dental pulp cells and may serve as a potential material for pulp repair and
      dentin regeneration.

PMID- 24576582
TI  - Reducing the rate of catheter-associated bloodstream infections in a surgical
      intensive care unit using the Institute for Healthcare Improvement Central Line
      Bundle.
AB  - BACKGROUND: Central line-associated bloodstream infections (CLABSIs) are a
      significant source of morbidity and mortality. This study sought to determine
      whether implementation of the Institute for Healthcare Improvement (IHI) Central
      Line Bundle would reduce the incidence of CLABSIs. METHODS: The IHI Central Line
      Bundle was implemented in a surgical intensive care unit. Patient demographics
      and the rate of CLABSIs per 1,000 catheter days were compared between the pre-
      and postintervention groups. Contemporaneous infection rates in an adjacent ICU
      were measured. RESULTS: Baseline demographics were similar between the pre- and
      postintervention groups. The rate of CLABSIs per catheter days decreased from
      19/3,784 to 3/1,870 after implementation of the IHI Bundle (1.60 vs 5.02 CLABSIs
      per 1,000 catheter days; rate ratio .32 [.08 to .99, P < .05]). There was no
      significant change in CLABSIs in the control ICU. CONCLUSIONS: Implementation of
      the IHI Central Line Bundle reduced the incidence of CLABSIs in our SICU by 68%,
      preventing 12 CLABSIs, 2.5 deaths, and saving $198,600 annually.

PMID- 24576583
TI  - Evaluating population-based breast cancer surgical practice in real time with a
      web-based synoptic operative reporting system.
AB  - BACKGROUND: A Web-based synoptic operative reporting system (WebSMR) incorporates
      implicit guidelines and real-time feedback of a surgeon's practice compared with
      provincial data. This study compares rates of total mastectomy (TM) between the
      overall provincial and WebSMR patients and examines decision-making factors in
      WebSMR patients. METHODS: Patients treated for invasive breast cancer (2007 to
      2011) were identified from WebSMR and the Alberta Cancer Registry. Reports
      include surgery type and reasons for TM. RESULTS: Among 5,787 patients in WebSMR
      (2007 to 2011), TM rate decreased from 48% to 42% (P < .001). In 2011, the
      provincial cancer registry recorded a 56% TM rate compared to 42% in WebSMR
      patients. Patient preference accounted for 36% in the latter group. CONCLUSIONS:
      In WebSMR patients, TM rates were lower than the overall provincial rate and
      decreased significantly during the study period. Reasons are unclear, but
      guidelines and real-time feedback likely plays a role.

PMID- 24576584
TI  - Conversations in disaster medicine and public health: the profession.
AB  - Using historical and research examples of disaster and crisis science, I argue
      here for the professionalization of disaster medicine and public health as a
      unique and essential discipline in support of global public health security.
      Questions about clinical competencies of providers and reports of unacceptable
      practices and the limited scope of guidelines for foreign medical teams have
      persisted for years. The professionalization movement endorses a standard route
      to certification through the completion of a competency-based curriculum,
      demonstrating competency through examination or experience to produce a learning
      and development portfolio, document competency through the acquisition of
      experience and added training, and develop professional associations. These
      programs devise certification criteria for entry, mid-level, and higher level
      candidates who serve in domestic and global humanitarian crises.

PMID- 24576585
TI  - Patient perspectives in the management of psoriasis: results from the population
      based Multinational Assessment of Psoriasis and Psoriatic Arthritis Survey.
AB  - BACKGROUND: Available psoriasis surveys offer valuable information about
      psoriasis and psoriatic arthritis (PsA), but are limited by methodology or
      enrollment requirements. OBJECTIVE: To further the understanding of the unmet
      needs of psoriasis and PsA patients. METHODS: This was a large, multinational,
      population-based survey of psoriasis and/or PsA patients in North America and
      Europe. Patients were selected by list-assisted random digit dialing and did not
      have to currently be under the care of a health care provider, a patient
      organization member, or receiving treatment; 139,948 households were screened and
      3426 patients completed the survey. RESULTS: The prevalence of psoriasis/PsA
      ranged from 1.4% to 3.3%; 79% had psoriasis alone and 21% had PsA. When rating
      disease severity at its worst, 27% (psoriasis) and 53% (PsA +/- psoriasis) of
      patients rated it as severe. Psoriasis patients indicated that their most
      bothersome signs or symptoms were itching (43%), scales (23%), and flaking (20%).
      Of psoriasis patients, 45% had not seen a physician in a year; >80% of psoriasis
      patients with >= 4 palms body surface area and 59% of PsA patients were receiving
      no treatment or topical treatment only. Of patients who had received oral or
      biologic therapy, 57% and 45%, respectively, discontinued therapy, most often for
      safety/tolerability reasons and a lack/loss of efficacy. LIMITATIONS: The survey
      lacked a control group, did not account for ethnic and health care system
      differences across countries, and was limited by factors associated with any
      patient survey, including accurate recall and interpretation of questions.
      CONCLUSIONS: Several identified unmet needs warrant additional attention and
      action, including improved severity assessment, PsA screening, patient awareness,
      and treatment options.

PMID- 24576586
TI  - Steeper posterior tibial slope markedly increases ACL force in both active gait
      and passive knee joint under compression.
AB  - The role of the posterior tibial slope (PTS) in anterior cruciate ligament (ACL)
      risk of injury has been supported by many imaging studies but refuted by some in
      vitro works. The current investigation was carried out to compute the effect of
      +/-5(o) change in PTS on knee joint biomechanics in general and ACL force/strain
      in particular. Two validated finite element (FE) models of the knee joint were
      employed; one active lower extremity musculoskeletal model including a complex FE
      model of the knee joint driven by in vivo kinematics/kinetics collected in gait
      of asymptomatic subjects, and the other its isolated unconstrained passive
      tibiofemoral (TF) joint considered under 1400 N compression at four different
      knee flexion angles (0 degrees -45 degrees ). In the TF model, the compression
      force was applied at the joint mechanical balance point causing no rotations in
      sagittal and frontal planes. Changes in PTS moderately affected muscle forces and
      joint contact forces at mid-stance period. Both active (at mid-stance) and
      passive (at all flexion angles) models showed a substantial increase in the
      anterior tibial translation and ACL force as PTS increased with reverse trends as
      PTS decreased. In the active model of gait at mid-stance, ACL force increased by
      75% (from 181 N to 317 N) in steeper PTS but decreased by 44% (to 102 N) in
      flatter PTS. The posterolateral bundle of ACL carried the load at smaller flexion
      angles with a shift to its anteromedial bundle as flexion increased. In
      accordance with earlier imaging studies, greater PTS is a major risk factor for
      ACL rupture especially in activities involving large compression forces.

PMID- 24576587
TI  - Biological variability in biomechanical engineering research: Significance and
      meta-analysis of current modeling practices.
AB  - Biological systems are characterized by high levels of variability, which can
      affect the results of biomechanical analyses. As a review of this topic, we first
      surveyed levels of variation in materials relevant to biomechanics, and compared
      these values to standard engineered materials. As expected, we found
      significantly higher levels of variation in biological materials. A meta-analysis
      was then performed based on thorough reviews of 60 research studies from the
      field of biomechanics to assess the methods and manner in which biological
      variation is currently handled in our field. The results of our meta-analysis
      revealed interesting trends in modeling practices, and suggest a need for more
      biomechanical studies that fully incorporate biological variation in
      biomechanical models and analyses. Finally, we provide some case study example of
      how biological variability may provide valuable insights or lead to surprising
      results. The purpose of this study is to promote the advancement of biomechanics
      research by encouraging broader treatment of biological variability in
      biomechanical modeling. 

PMID- 24576588
TI  - The control of twisting somersaults.
AB  - In the takeoff and early flight phase of a twisting somersault, joint
      coordination is based on feed-forward control whereas in the late stages of the
      flight phase configuration adjustments are made using feedback control to ensure
      accurate completion of the movement and appropriate landing orientation. The aim
      of this study was to use a computer simulation model of aerial movement to
      investigate the extent to which arm and hip movements can control twist and
      somersault rotation in the flight phase of a twisting somersault. Two mechanisms
      were considered for the control of twist in simulated target trampoline movements
      with flight times of 1.4s. In the first case a single symmetrical arm adduction
      correction was made using delayed feedback control based on the difference
      between the twist rate in a perturbed simulation and the twist rate in a target
      movement comprising a forward somersault with 11/2 twists. Final corrections were
      made using symmetrical arm abduction and hip flexion to adjust the twist and
      somersault angles. In the second case continual asymmetrical arm
      adduction/abduction adjustments were used to remove the tilt from a perturbed
      full twisting backward somersault using delayed feedback control based on twist
      angle and angular velocity. The first method was able to cope with perturbations
      to a forward somersault with 11/2 twists providing the feedback time delay was
      less than 200 ms. The second method was able to correct a perturbed full twisting
      backward somersault providing the feedback time delay was less than 125 ms.

PMID- 24576589
TI  - Geriatric Anxiety Scale: item response theory analysis, differential item
      functioning, and creation of a ten-item short form (GAS-10).
AB  - BACKGROUND: The Geriatric Anxiety Scale (GAS; Segal et al. (Segal, D. L., June,
      A., Payne, M., Coolidge, F. L. and Yochim, B. (2010). Journal of Anxiety
      Disorders, 24, 709-714. doi:10.1016/j.janxdis.2010.05.002) is a self-report
      measure of anxiety that was designed to address unique issues associated with
      anxiety assessment in older adults. This study is the first to use item response
      theory (IRT) to examine the psychometric properties of a measure of anxiety in
      older adults. METHOD: A large sample of older adults (n = 581; mean age = 72.32
      years, SD = 7.64 years, range = 60 to 96 years; 64% women; 88% European American)
      completed the GAS. IRT properties were examined. The presence of differential
      item functioning (DIF) or measurement bias by age and sex was assessed, and a ten
      item short form of the GAS (called the GAS-10) was created. RESULTS: All GAS
      items had discrimination parameters of 1.07 or greater. Items from the somatic
      subscale tended to have lower discrimination parameters than items on the
      cognitive or affective subscales. Two items were flagged for DIF, but the impact
      of the DIF was negligible. Women scored significantly higher than men on the GAS
      and its subscales. Participants in the young-old group (60 to 79 years old)
      scored significantly higher on the cognitive subscale than participants in the
      old-old group (80 years old and older). CONCLUSIONS: Results from the IRT
      analyses indicated that the GAS and GAS-10 have strong psychometric properties
      among older adults. We conclude by discussing implications and future research
      directions.

PMID- 24576590
TI  - Deployment and release of interhemispheric inhibition in dual-stream rapid serial
      visual presentation.
AB  - When one of the two hemispheres directs visuospatial attention to some
      contralateral location, this may imply that inhibition is exerted on the other
      hemisphere. In the dual rapid serial visual presentation task, two targets (T1
      and T2) occur among two different visual streams, rapidly presented left and
      right. We replaced the standard letter distractors in one stream by "easy
      symbols" (ESy; easily distinguished from targets), to facilitate T1
      identification. If interhemispheric inhibition is deployed and released, this
      facilitation of one hemisphere's task should reduce its inhibitory effect on the
      other hemisphere, leading to improved T2 identification by the other hemisphere.
      This prediction was confirmed in three experiments. Furthermore, event-related
      EEG potentials did not only show a constant bias of allocated attention between
      ESy and standard streams, with letters evoking visual potentials earlier than
      ESy, but also short-term enlargement of this effect in the pair of distractors
      that followed T1. Taken together, these results support the notion of
      interhemispheric inhibition in visuospatial attention. 

PMID- 24576591
TI  - Synthesis, in vitro anticancer evaluation and in silico studies of novel
      imidazo[2,1-b]thiazole derivatives bearing pyrazole moieties.
AB  - A series of imidazo[2,1-b]thiazoles bearing pyrazole moieties 4-6(a-c) was
      synthesized through the reaction of 6-hydrazinylimidazo[2,1-b]thiazoles 3a-c with
      different beta-dicarbonyl compounds. Eleven compounds were screened at the
      National Cancer Institute (NCI), USA for anticancer activity at a single dose (10
      MUM). The in vitro anticancer evaluation revealed that compounds 2a and 4-6(a)
      exhibited increased potency towards CNS SNB-75 and Renal UO-31 cancer cell lines.
      COMPARE analyses showed strong to considerable correlations with rapamycin (mTOR
      inhibitor). The results of assessment of toxicities, druglikeness, and drug score
      profiles of compounds 2a and 4-6(a) are promising. Some of the target compounds
      showed good docking scores with potential anticancer targets, chosen based on
      pharmacophore mapping of the established derivatives.

PMID- 24576592
TI  - Malignant melanoma of the gastro-intestinal tract: a case series.
AB  - BACKGROUND: Resection of gastrointestinal (GI) metastases of malignant melanoma
      (MM) offers a significant survival benefit. No adjuvant therapy has been shown to
      be effective in the treatment of these metastases. METHODS: All resections of MM
      affecting the GI tract at a UK University teaching hospital between October 1999
      and January 2013 were identified from a pathology database. Demographic,
      investigative, operative and outcome data were retrieved from hospital records.
      Survival analysis was performed. RESULTS: Thirty patients were identified (median
      age 62.7 years). 3 patients underwent a second operation at a later date to
      resect further metastases. 6 patients (20.0%) presented with no identifiable
      cutaneous lesion. The average time to GI metastases was 52.0 months (range 4.9
      139.8 months) for those with an identified cutaneous primary (n = 24). Two
      patients with initial cutaneous lesions with Breslow's thickness <1 mm developed
      GI metastases. Common presenting symptoms included abdominal pain (n = 8, 27.6%),
      GI bleeding (n = 5, 17.2%) and symptoms of GI tract obstruction (n = 4, 13.8%).
      CT scan was the most commonly performed investigation (96.6%). Over half of
      resections (54.5%, n = 18) included small bowel resection. Mortality at 2 and 5
      years was 66.4% and 73.1%. Of the 3 patients who underwent a second resection of
      GI metastases, one is still alive after 26 months of follow up; 2 patients died
      after 32.8 and 18.6 months. CONCLUSIONS: Clinicians should have a low threshold
      for investigating GI symptoms in patients with a history of malignant melanoma
      even in the case of early-stage primary disease. Re-resection should be
      considered in patients presenting with further GI metastases.

PMID- 24576593
TI  - A network meta-analysis on the efficacy of 5-aminosalicylates, immunomodulators
      and biologics for the prevention of postoperative recurrence in Crohn's disease.
AB  - BACKGROUND AND AIMS: A number of agents have been evaluated in clinical trials to
      reduce the risk of postoperative recurrence in Crohn's disease (CD). The aim of
      this study was to compare the efficacy of 5-aminosalicylates, immunomodulators
      and biologics for postoperative prophylaxis of CD recurrence by using a network
      meta-analytical approach. METHODS: PubMed, Embase, and Cochrane Library were
      searched (update to November 2013) to identify randomized placebo-controlled, or
      head-to-head trials among the three drug classes for prevention of postoperative
      CD relapse. The primary endpoint for efficacy was endoscopic recurrence, and the
      secondary outcomes were clinical recurrence and adverse events. We conducted a
      Bayesian network meta-analysis with a mixed treatment comparisons to combine both
      direct and indirect evidences. RESULTS: Fifteen trials involving 1507 patients
      were included in this analysis. Biological agents were associated with a large
      and significant reduction of both endoscopic and clinical recurrence compared
      with placebo, 5-aminosalicylates, or immunomodulators. Immunomodulators showed
      greater efficacy in terms of endoscopic and clinical recurrence prophylaxis
      compared with 5-aminosalicylates or placebo, but with higher incidence of adverse
      events. 5-aminosalicylates were superior to placebo for prevention of clinical
      recurrence, without increasing the rate of side effect. CONCLUSIONS: 5
      aminosalicylates, immunomodulators, and biologics are more efficacious than
      placebo for postoperative CD prevention. Biologics are found to be the most
      effective medications to prevent CD recurrence.

PMID- 24576594
TI  - tPA promotes ADAMTS-4-induced CSPG degradation, thereby enhancing neuroplasticity
      following spinal cord injury.
AB  - Although tissue plasminogen activator (tPA) is known to promote neuronal
      remodeling in the CNS, no mechanism of how this plastic function takes place has
      been reported so far. We provide here in vitro and in vivo demonstrations that
      this serine protease neutralizes inhibitory chondroitin sulfate proteoglycans
      (CSPGs) by promoting their degradation via the direct activation of endogenous
      type 4 disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS-4).
      Accordingly, in a model of compression-induced spinal cord injury (SCI) in rats,
      we found that administration of either tPA or its downstream effector ADAMTS-4
      restores the tPA-dependent activity lost after the SCI and thereby, reduces
      content of CSPGs in the spinal cord, a cascade of events leading to an improved
      axonal regeneration/sprouting and eventually long term functional recovery. This
      is the first study to reveal a tPA-ADAMTS-4 axis and its function in the CNS. It
      also raises the prospect of exploiting such cooperation as a therapeutic tool for
      enhancing recovery after acute CNS injuries. 

PMID- 24576595
TI  - A novel gene therapy vector based on hyaluronic acid and solid lipid
      nanoparticles for ocular diseases.
AB  - The introduction of therapeutic genes in target tissues is considered as a novel
      tool for the treatment of several diseases. We have developed nanoparticles
      consisting on SLNs, protamine (P) and hyaluronic acid (HA) as carrier for gene
      therapy. Stable complexes positively charged and with a particle size ranging
      from 240 nm to 340 nm were obtained. Transfection studies in ARPE-19 and HEK-293
      cells showed the versatility of vectors to efficiently transfect cells with
      different division rate, widening the potential applications of SLN-based
      vectors. In ARPE 19cells, the incorporation of P and HA induced almost a 7-fold
      increase in the transfection capacity of SLNs. The CD44 inhibition studies
      suggested the participation of this receptor in the internalization of the
      vectors in this cell line. The intracellular disposition of DNA showed that the
      HA is able to modulate the high degree of condensation of DNA due to the
      protamine inside the cells; an important fact, if the vector is uptaken via non
      degradative endocytosis. Besides, the therapeutic plasmid which encodes the
      protein retinoschisin was employed achieving a positive transfection in ARPE-19
      cells, showing a promising application of this new non-viral system for the
      treatment of X-linked juvenile retinoschisis by gene therapy.

PMID- 24576596
TI  - Peptide hydrogels as mucoadhesives for local drug delivery.
AB  - We have investigated the possibility of using self-assembling peptide-based
      viscous solutions and hydrogels as mucoadhesives for the improved delivery of
      drugs to local mucosal surfaces. The stability of the samples under flow after
      deposition on a mucosal surface mimic was studied using a simplified in vitro
      model. Subsequently lidocaine and flurbiprofen, two commercial drugs, were
      incorporated into the viscous solutions and hydrogels and their release
      properties investigated using the same model. Peptide-based hydrogels showed a
      good resistance to erosion under flow conditions. Addition of the soluble drug
      (lidocaine at low pH) resulted in a stiffening of the samples but did not affect
      the overall peptide release. Although for this drug the conditions were not
      favourable, improved retention of the drug was observed for the stiffest samples
      tested. In the case of the insoluble drug (flurbiprofen) the samples mechanical
      properties were not altered when the drug was incorporated, however the sample
      stability and peptide release were. For mechanically weaker samples the presence
      of the drug as insoluble small particles resulted in an increase in their
      susceptibility to physically erode when a flow of medium was applied over its
      surface. On the other hand mechanically stronger samples showed an improved
      resistance to erosion, which resulted in enhanced drug retention. 

PMID- 24576599
TI  - Mode perturbation method for optimal guided wave mode and frequency selection.
AB  - With a thorough understanding of guided wave mechanics, researchers can predict
      which guided wave modes will have a high probability of success in a particular
      nondestructive evaluation application. However, work continues to find optimal
      mode and frequency selection for a given application. This "optimal" mode could
      give the highest sensitivity to defects or the greatest penetration power,
      increasing inspection efficiency. Since material properties used for modeling
      work may be estimates, in many cases guided wave mode and frequency selection can
      be adjusted for increased inspection efficiency in the field. In this paper, a
      novel mode and frequency perturbation method is described and used to identify
      optimal mode points based on quantifiable wave characteristics. The technique
      uses an ultrasonic phased array comb transducer to sweep in phase velocity and
      frequency space. It is demonstrated using guided interface waves for bond
      evaluation. After searching nearby mode points, an optimal mode and frequency can
      be selected which has the highest sensitivity to a defect, or gives the greatest
      penetration power. The optimal mode choice for a given application depends on the
      requirements of the inspection. 

PMID- 24576598
TI  - Design of a consensus-derived synoptic operative report for lung cancer surgery.
AB  - BACKGROUND: For lung cancer surgery, a narrative operative report is the standard
      reporting procedure, whereas a synoptic-style report is increasingly utilized by
      healthcare professionals in various specialties with great success. A synoptic
      operative report more succinctly and accurately captures vital information and is
      rapidly generated with good intraobserver reliability. The objective of this
      study was to systematically develop a synoptic operative report for lung cancer
      surgery following a modified Delphi consensus model with the support of the
      Canadian thoracic surgery community. METHODS: Using online survey software,
      thoracic surgeons and related physicians were asked to suggest and rate data
      elements for a synoptic report following the modified Delphi consensus model. The
      consensus exercise-derived template was forwarded to a small working group, who
      further refined the definition and priority designation of elements until the
      working group had reached a satisfactory consensus. RESULTS: In all, 139
      physicians were invited to participate in the consensus exercise, with 36.7%,
      44.6%, and 19.5% response rates, respectively, in the three rounds. Eighty-nine
      elements were agreed upon at the conclusion of the exercise, but 141 elements
      were forwarded to the working group. The working group agreed upon a final data
      set of 180 independently defined data elements, with 72 mandatory and 108
      optional elements for implementation in the final report. CONCLUSIONS: This study
      demonstrates the process involved in developing a multidisciplinary, consensus
      based synoptic lung cancer operative report. This novel report style is a quality
      improvement initiative to improve the capture, dissemination, readability, and
      potential utility of critical surgical information.

PMID- 24576597
TI  - Accuracy of fluorodeoxyglucose-positron emission tomography within the clinical
      practice of the American College of Surgeons Oncology Group Z4031 trial to
      diagnose clinical stage I non-small cell lung cancer.
AB  - BACKGROUND: Fluorodeoxyglucose-positron emission tomography (FDG-PET) is
      recommended for diagnosis and staging of non-small cell lung cancer (NSCLC). Meta
      analyses of FDG-PET diagnostic accuracy demonstrated sensitivity of 96% and
      specificity of 78% but were performed in select centers, introducing potential
      bias. This study evaluates the accuracy of FDG-PET to diagnose NSCLC and examines
      differences across enrolling sites in the national American College of Surgeons
      Oncology Group (ACOSOG) Z4031 trial. METHODS: Between 2004 and 2006, 959 eligible
      patients with clinical stage I (cT1-2 N0 M0) known or suspected NSCLC were
      enrolled in the Z4031 trial, and with a baseline FDG-PET available for 682. Final
      diagnosis was determined by pathologic examination. FDG-PET avidity was
      categorized into avid or not avid by radiologist description or reported maximum
      standard uptake value. FDG-PET diagnostic accuracy was calculated for the entire
      cohort. Accuracy differences based on preoperative size and by enrolling site
      were examined. RESULTS: Preoperative FDG-PET results were available for 682
      participants enrolled at 51 sites in 39 cities. Lung cancer prevalence was 83%.
      FDG-PET sensitivity was 82% (95% confidence interval, 79 to 85) and specificity
      was 31% (95% confidence interval, 23% to 40%). Positive and negative predictive
      values were 85% and 26%, respectively. Accuracy improved with lesion size. Of 80
      false-positive scans, 69% were granulomas. False-negative scans occurred in 101
      patients, with adenocarcinoma being the most frequent (64%), and 11 were 10 mm or
      less. The sensitivity varied from 68% to 91% (p=0.03), and the specificity ranged
      from 15% to 44% (p=0.72) across cities with more than 25 participants.
      CONCLUSIONS: In a national surgical population with clinical stage I NSCLC, FDG
      PET to diagnose lung cancer performed poorly compared with published studies.

PMID- 24576600
TI  - Generation of transversal envelope soliton in polymeric and wooden rods.
AB  - This paper is concerned with the probing of the transversal envelope solitons
      propagation in circular waveguides when a set of requirements (non-linearity and
      dispersion) are fulfilled in the waveguide and balanced. The basic idea is to
      analyze the shape of an acoustic pulse after it has traveled one or few trips
      through samples constituted of a rod and two ended beads. The dispersive behavior
      is associated to the bounded medium (rod) and the contacts between the elements
      of the specimens are assumed being described by non-linear Hertz' law type. The
      experimental data are obviously material dependent and have pointed out the
      existence of common properties on the formation and propagation properties of the
      envelope solitons whatever is the material (polymers, carbon fibers and wood) of
      the rods and spheres. Peculiar behaviors were also observed for specific material
      (woods) probably caused by the anisotropy of this kind of rod material leading to
      a double envelope soliton. 

PMID- 24576602
TI  - Development of an egg hatch assay for the detection of anthelmintic resistance to
      albendazole in Fasciola hepatica isolated from sheep.
AB  - The aim of this study was to develop an egg hatch assay (EHA) to detect the
      resistance of Fasciola hepatica to albendazole (ABZ). With this purpose, two
      different F. hepatica isolates were tested: (i) susceptible (Shrewsbury/South
      Gloucester strain) to ABZ (SA); (ii) resistant to ABZ (RA). A commercial
      formulation of ABZ (Sinvermin) diluted in dimethyl sulfoxide (DMSO) was used at
      concentrations of 0.0002, 0.002, 0.02, 0.2, and 2 MUg/ml. In the SA isolates,
      eggs from feces exposed to ABZ at the three highest concentrations showed
      significantly lower hatching percentages than the control well (P<0.01); also for
      the two highest concentrations, the percentage of development was significantly
      lower than the control (P<0.01). However, in the RA isolate, no differences among
      treatments and control were found in the percentage of hatched or developed eggs.
      On the other hand, the EHA was conducted over a 15 day period following treatment
      with ABZ for sheep infected by the RA isolate. On day 7 post-treatment (pt), no
      differences among treatments and controls were observed. On day 15 pt, the
      development and hatching rates exposed to the highest ABZ concentration were
      lower than at lower concentrations, suggesting susceptibility. The ovicidal
      effect of ABZ and the potential use of EHA to differentiate between ABZ
      susceptible and resistant isolates are confirmed in the current study. However,
      the use of this technique should be confirmed with a higher number of isolates.

PMID- 24576604
TI  - Introducing a catheter-associated urinary tract infection (CAUTI) prevention
      guide to patient safety (GPS).
AB  - Catheter-associated urinary tract infection, 1 of the hospital-acquired
      conditions targeted for reduction by the US government, is challenging to
      prevent. We therefore developed a self-assessment tool (a catheter-associated
      urinary tract infection prevention guide to patient safety) based on extensive
      qualitative evaluations. We describe the rationale, features, and utility of such
      a quality improvement tool. 

PMID- 24576603
TI  - Pre-treatment with heat facilitates detection of antigen of Dirofilaria immitis
      in canine samples.
AB  - Diagnosis of Dirofilaria immitis infection in dogs is largely dependent on
      detection of antigen in canine serum, plasma, or whole blood, but antigen may be
      bound in immune complexes and thus not detected. To develop a model for antigen
      blocking, we mixed serum from a microfilaremic, antigen-positive dog with that of
      a hypergammaglobulinemic dog not currently infected with D. immitis and converted
      the positive sample to antigen-negative; detection of antigen was restored when
      the mixed sample was heat-treated, presumably due to disruption of
      antigen/antibody complexes. A blood sample was also evaluated from a dog that was
      microfilaremic and for which microfilariae were identified as D. immitis by
      morphologic examination. Antigen of D. immitis was not detected in this sample
      prior to heating but the sample was strongly positive after heat treatment of
      whole blood. Taken together, our results indicate that blood samples from some
      dogs may contain factors that inhibit detection of antigen of D. immitis, and
      that heat treatment of these samples prior to testing could improve the
      sensitivity of these assays in some patients. 

PMID- 24576605
TI  - Antiparallel conformation of knob and hole aglycosylated half-antibody homodimers
      is mediated by a CH2-CH3 hydrophobic interaction.
AB  - Bispecific antibody and antibody-like molecules are of wide interest as potential
      therapeutics that can recognize two distinct targets. Among the variety of ways
      such molecules have been engineered is by creating "knob" and "hole"
      heterodimerization sites in the CH3 domains of two antibody heavy chains. The
      molecules produced in this manner maintain their biological activities while
      differing very little from the native human IgG sequence. To better understand
      the knob-into-hole interface, the molecular mechanism of heterodimerization, and
      to engineer Fc domains that could improve the assembly and purity of
      heterodimeric reaction products, we sought crystal structures of aglycosylated
      heterodimeric and homodimeric "knob" and "hole" Fc fragments derived from
      bacterial expression. The structure of the knob-into-hole Fc was determined at
      2.64 A. Except for the sites of mutation, the structure is very similar to that
      of the native human IgG1 Fc, consistent with a heterodimer interaction kinetic
      K(D) of <1 nM. Homodimers of the "knob" and "hole" mutants were also obtained,
      and their X-ray structures were determined at resolutions 2.5 A and 2.1 A,
      respectively. Both kinds of homodimers adopt a head-to-tail quaternary structure
      and thus do not contain direct knob/knob or hole/hole CH3 interactions. The head
      to-tail arrangement was disfavored by adding site-directed mutations at F241 and
      F243 in the CH2 domains, leading to increases in both rate and efficiency of
      bispecific (heterodimer) assembly.

PMID- 24576606
TI  - Context-dependent remodeling of Rad51-DNA complexes by Srs2 is mediated by a
      specific protein-protein interaction.
AB  - The yeast Srs2 helicase removes Rad51 nucleoprotein filaments from single
      stranded DNA (ssDNA), preventing DNA strand invasion and exchange by homologous
      recombination. This activity requires a physical interaction between Srs2 and
      Rad51, which stimulates ATP turnover in the Rad51 nucleoprotein filament and
      causes dissociation of Rad51 from ssDNA. Srs2 also possesses a DNA unwinding
      activity and here we show that assembly of more than one Srs2 molecule on the 3'
      ssDNA overhang is required to initiate DNA unwinding. When Rad51 is bound on the
      double-stranded DNA, its interaction with Srs2 blocks the helicase (DNA
      unwinding) activity of Srs2. Thus, in different DNA contexts, the physical
      interaction of Rad51 with Srs2 can either stimulate or inhibit the remodeling
      functions of Srs2, providing a means for tailoring DNA strand exchange activities
      to enhance the fidelity of recombination. 

PMID- 24576607
TI  - Implementing national guidelines for person-centered care of people with dementia
      in residential aged care: effects on perceived person-centeredness, staff strain,
      and stress of conscience.
AB  - BACKGROUND: Person-centeredness has had substantial uptake in the academic
      literature on care of older people and people with dementia. However, challenges
      exist in interpreting and synthesizing the evidence on effects of providing
      person-centered care, as the person-centered components of some intervention
      studies are unclear - targeting very different and highly specific aspects of
      person-centeredness, as well as not providing empirical data to indicate the
      extent to which care practice was actually perceived to become more person
      centered post-intervention. METHODS: The study employed a quasi-experimental, one
      group pre-test-post-test design with a 12-month follow-up to explore intervention
      effects on person-centeredness of care and the environment (primary endpoints),
      and on staff strain and stress of conscience (secondary endpoints). RESULTS: The
      intervention resulted in significantly higher scores on person-centeredness of
      care at follow-up, and the facility was rated as being significantly more
      hospitable at follow-up. A significant reduction of staff stress of conscience
      was also found at follow-up, which suggests that, to a larger extent, staff could
      provide the care and activities they wanted to provide after the intervention.
      CONCLUSIONS: The results indicated that an interactive and step-wise action
      research intervention consisting of knowledge translation, generation, and
      dissemination, based on national guidelines for care of people with dementia,
      increased the staff self-reported person-centeredness of care practice, perceived
      hospitality of the setting, and reduced staff stress of conscience by enabling
      staff to provide the care and activities they want to provide.

PMID- 24576608
TI  - Development of surface imprinted core-shell nanoparticles and their application
      in a solid-phase dispersion extraction matrix for methyl parathion.
AB  - Applying molecular imprinting techniques to the surface of functionalized SiO2
      allows the preparation of molecularly imprinted polymers (MIPs) with accessible,
      high affinity and surface exposed binding sites. This paper demonstrates a new
      strategy for producing such hybrid organic-inorganic surface imprinted silica
      nanoparticles for specific recognition of methyl parathion. The technique
      provides surface grafting imprinting in chloroform using amino modified silica
      nanoparticles as supports, acrylamide as the functional monomer, gamma
      methacryloxypropyl trimethoxy silane as the grafting agent, and methyl parathion
      as a template. The amino propyl functional monomer layer directs the selective
      occurrence of imprinting polymerization at the silica surface through
      copolymerization of grafting agents with functional monomers, but also acts as an
      assistive monomer to drive the template into the formed polymer shells to create
      effective recognition sites. The resulting MIPs-SiO2 nanoparticles display three
      dimensional core-shell architectures and large surface areas. The molecularly
      imprinted shell provides recognition sites for methyl parathion, with the
      materials exhibiting excellent performance for selecting the template. Using MIPs
      SiO2 nanoparticles as a matrix of solid-phase dispersion extraction sorbents,
      trace amounts of methyl parathion are selectivity extracted from pear and green
      vegetable samples while simultaneously eliminating matrix interferences,
      attaining recoveries of 84.7-94.4% for the samples. 

PMID- 24576609
TI  - Presenting symptoms in adults with the 22q11 deletion syndrome.
AB  - A definitive molecular diagnosis of 22q11 Deletion Syndrome (22q11DS) even if
      occurring later in life, has important genetic, medical and emotional impact on
      the patients and their families. The aim of this study is to describe presenting
      symptoms and age at diagnosis in an adult 22q11DS population. A retrospective
      study was performed on 65 individuals diagnosed with 22q11DS at adult age. Data
      were collected on adults referred to the genetic clinic or actively recruited
      through systematic diagnostic examination in both institutions and a psychiatric
      unit for intellectually disabled. Presenting symptoms were categorized into seven
      groups: familial occurrence, intellectual disability, cardiac anomalies, palatal
      anomalies, facial dysmorphic features, psychiatric problems and 'other'
      (comprising all other features associated with 22q11DS). Age at diagnosis was
      defined as the age at which the 22q11.2 deletion was detected by fluorescence in
      situ hybridization or comparative genomic hybridization. Ascertainment subgroups
      were different in presenting symptoms and age at diagnosis. Adults were referred
      to the genetic clinic mainly because of familial occurrence, cardiac defects and
      psychiatric disorders whereas adults diagnosed in institutions for intellectually
      disabled presented mainly with moderate to severe intellectual disability and
      psychotic disorders. Adults diagnosed at the psychiatric unit for intellectually
      disabled had a variety of psychiatric disorders but none of them had additional
      physical features. This emphasizes the need to stay alert for presenting symptoms
      such as conotruncal heart defects or moderate to severe intellectual disability
      in combination with a history of psychiatric disorders, even in the absence of
      obvious physical features. 

PMID- 24576612
TI  - Benzothiazoles exhibit broad-spectrum antitumor activity: their potency,
      structure-activity and structure-metabolism relationships.
AB  - An antitumor activity oriented benzothiazole sublibrary was constructed from a
      hit compound 3 via a five stepwise procedure. All target compounds were screened
      for their antitumor activity against 60 human cancer cell lines. Compounds 9p,
      12d and 12i, showing higher potency than hit 3, were identified. Particularly,
      the compound 9p gave its average 50% growth inhibition (GI50) at 0.38 MUM.
      Furthermore, incubation in human liver microsome primarily proved their metabolic
      stability in vitro. General structure-activity and structure-metabolism
      relationships were both summarized, which provides information on further
      strategically optimization.

PMID- 24576610
TI  - Descriptive and risk factor analysis for choanal atresia: The National Birth
      Defects Prevention Study, 1997-2007.
AB  - Choanal atresia causes serious posterior nasal obstruction. This defect is the
      leading cause of nasal surgery in newborns, although its etiology is largely
      unknown. Data from the National Birth Defects Prevention Study, a population
      based case-control study, were used to examine associations between maternal self
      reports of exposures and occurrence of choanal atresia in their offspring.
      Overall, 117 case and 8350 control mothers with deliveries from 1997 through 2007
      provided telephone interview reports of pre-pregnancy (one year before
      conception) and periconceptional (one month before through three months after
      conception) exposures. The exposures analyzed were pre-pregnancy dietary intake,
      pre-pregnancy and periconceptional caffeine consumption, and periconceptional
      cigarette smoking, alcohol drinking, and medication use. Independent associations
      between each exposure and all choanal atresia cases combined (n = 117) and
      isolated choanal atresia cases (those without additional unrelated major defects;
      n = 61) were examined. Odds ratios (ORs), both unadjusted (uORs) and adjusted
      (aORs) for potential confounders, and 95% confidence intervals (CIs) were
      estimated using unconditional logistic regression analysis. For all choanal
      atresia cases combined, positive associations were observed with maternal pre
      pregnancy intake in the highest quartile for vitamin B-12 (aOR = 1.9; CI =
      1.1,3.1), zinc (aOR = 1.7; CI = 1.0,3.1), and niacin (aOR = 1.8; CI = 1.0,3.1),
      and intake in the lowest quartile for methionine (aOR = 1.6; CI = 1.0,2.6) and
      vitamin D (aOR = 1.6; CI = 1.0,2.4) compared to intake in the two intermediate
      quartiles combined. Further, a positive association was observed with
      periconceptional use of thyroid medications (uOR = 2.6; CI = 1.0,6.3) compared to
      no use of such medications. Among isolated choanal atresia cases, negative
      associations were observed for pantothenic acid (aOR = 0.4; CI = 0.2,0.9) and fat
      (aOR = 0.5; 95% CI = 0.2,1.0) intake in the lowest quartile compared to that in
      the intermediate quartiles, and positive associations were observed for
      periconceptional cigarette smoking (aOR = 2.3; CI = 1.1,4.7) compared to no
      smoking and pre-pregnancy daily coffee intake of 3 or more cups (aOR = 2.5; CI =
      1.1,5.6) compared to intake of less than 1 cup per day. The positive association
      for periconceptional exposure to thyroid medications also persisted for isolated
      choanal atresia cases (uOR = 4.0; CI = 1.1,11.2). Because of the large number of
      associations tested, these findings may be due to chance. Alternatively, they may
      contribute new hypotheses regarding the etiology of choanal atresia; thus,
      requiring replication in additional studies.

PMID- 24576611
TI  - Development of adrenal cortical zonation and expression of key elements of
      adrenal androgen production in the chimpanzee (Pan troglodytes) from birth to
      adulthood.
AB  - The basis for the pattern of adrenal androgen production in the chimpanzee, which
      resembles that of humans, is poorly defined. We characterized the developmental
      zonation and expression of elements of the androgen biosynthetic pathway in the
      chimpanzee adrenal. The newborn adrenal contained a broad fetal zone (FZ)
      expressing CYP17, SULT2A1, and Cytochrome B5 (CB5) but not HSD3B; the outer
      cortex expressed HSD3B but not SULT2A1 or CB5. During infancy, the FZ involuted
      and the HSD3B-expressing outer cortex broadened. By 3years of age, a thin layer
      of cells that expressed CB5, SULT2A1, and CYP17 adjoined the medulla and likely
      represented the zona reticularis; the outer cortex consisted of distinct zonae
      fasiculata and glomerulosa. Thereafter, the zona reticularis broadened as also
      occurs in the human. The adult chimpanzee adrenal displayed other human-like
      characteristics: intramedullary clusters of reticularis-like cells and also a
      cortical cuff of zona fasiculata-like cells adjoining the central vein. 

PMID- 24576613
TI  - Synthesis of coumarin derivatives as fluorescent probes for membrane and cell
      dynamics studies.
AB  - Three coumarin-derived fluorescent probes, 3-acetyl-7-[(6-bromohexyl)oxy]-2H
      chromen-2-one (FM1), 7-[(6-bromohexyl)oxy]-4-methyl-2H-chromen-2-one (FM2) and
      ethyl 2-{7-[(6-bromohexyl)oxy]-2-oxo-2H-chromen-4-yl}acetate (FM3), are
      described, with their photophysical constants. The compounds were tested in
      preliminary studies employing epifluorescence microscopy demonstrating that they
      allow the imaging of human neuroblastoma SH-SY5Y cell membranes. The structure of
      FM3 was confirmed by X-ray crystallographic analysis. Molecular dynamics (MD)
      simulations were used to characterize the localization and interactions of the
      studied compounds with a lipid bilayer model of 1-palmitoyl-2-oleoyl-sn-glycero-3
      phosphocholine (POPC). 

PMID- 24576614
TI  - The multiplier role of psychiatrists in low income settings.
AB  - Mental health care is receiving increased attention in low-income countries with
      the availability of a wide range of effective evidence-based treatments for acute
      and chronic mental disorders amidst scarce resources. Availability of these
      treatments and competent human resources enables the use of a variety of
      interventions at several levels of care for persons with mental illness and makes
      it feasible to ensure observance of quality in the treatment approaches that go
      beyond institutionalisation. However, unlike developed countries which are
      endowed with many and relatively well-paid mental health specialists, low-income
      countries face a dire shortage of highly trained mental health professionals in
      addition to several other challenges. In light of this, there is need to re
      assess the role of the few available psychiatrists, with a shift to new core
      tasks such as designing mental health care programmes that can be delivered by
      non-specialists, building their health system's capacity for delivering care,
      including supporting front-line health workers through support supervision,
      raising awareness on mental health and patients' rights in addition to promoting
      essential research. This requires a fundamental paradigm shift from the current
      training for mental health specialists to a public health oriented approach and
      providing incentives for community engagement. 

PMID- 24576615
TI  - Heart rate variability and alternans formation in the heart: The role of feedback
      in cardiac dynamics.
AB  - A beat-to-beat alternation in the action potential duration (APD) of myocytes,
      i.e. alternans, is believed to be a direct precursor of ventricular fibrillation
      in the whole heart. A common approach for the prediction of alternans is to
      construct the restitution curve, which is the nonlinear functional relationship
      between the APD and the preceding diastolic interval (DI). It was proposed that
      alternans appears when the magnitude of the slope of the restitution curve
      exceeds one, known as the restitution hypothesis. However, this restitution
      hypothesis was derived under the assumption of periodic stimulation, when there
      is a dependence of the DI on the immediate preceding APD (i.e. feedback).
      However, under physiological conditions, the heart rate exhibits substantial
      variations in time, known as heart rate variability (HRV), which introduces
      deviations from periodic stimulation in the system. In this manuscript, we
      investigated the role of HRV on alternans formation in isolated cardiac myocytes
      using numerical simulations of an ionic model of the cardiac action potential. We
      used this model with two different pacing protocols: a periodic pacing protocol
      with feedback and a protocol without feedback. We show that when HRV is
      incorporated in the periodic pacing protocol, it facilitated alternans formation
      in the isolated cell, but did not significantly change the magnitude of
      alternans. On the other hand, in the case of the pacing protocol without
      feedback, alternans formation was prevented, even in the presence of HRV.

PMID- 24576616
TI  - Cost savings in plastic surgery: boardless skin meshers?

PMID- 24576617
TI  - CRISPR/Cas9 mediated genome engineering in Drosophila.
AB  - Genome engineering has revolutionised genetic analysis in many organisms. Here we
      describe a simple and efficient technique to generate and detect novel mutations
      in desired target genes in Drosophila melanogaster. We target double strand
      breaks to specific sites within the genome by injecting mRNA encoding the Cas9
      endonuclease and in vitro transcribed synthetic guide RNA into Drosophila
      embryos. The small insertion and deletion mutations that result from inefficient
      non-homologous end joining at this site are detected by high resolution melt
      analysis of whole flies and individual wings, allowing stable lines to be made
      within 1 month.

PMID- 24576619
TI  - Sustained stimulation and expansion of Tregs by IL2 control autoimmunity without
      impairing immune responses to infection, vaccination and cancer.
AB  - Interleukin 2 (IL2) is the key cytokine supporting survival and function of
      regulatory T cells (Tregs). We recently reported that low-dose IL2 safely
      expands/stimulates Tregs and improves autoimmune conditions in humans. Further
      development of IL2 in autoimmune diseases will require chronic IL2
      administration, which could affect beneficial effector immune responses regulated
      by Tregs. We used recombinant adeno-associated viral vector (rAAV)-mediated gene
      transfer to continuously release IL2 in mice and assessed its long-term effects
      on immune responses. A single rAAV-IL2 injection enabled sustained stimulation
      and expansion of Tregs without inducing Teff activation and prevented diabetes in
      NOD mice. After several weeks of IL2 production, mice responded normally to a
      viral challenge and to vaccination, and had pregnancies with offspring that
      developed normally. They showed no change in the occurrence and growth of
      chemically-induced tumors. Altogether, chronic low-dose IL2 treatment does not
      affect beneficial effector immune responses at doses that prevent autoimmune
      diabetes. 

PMID- 24576618
TI  - RNAi screening in Drosophila cells and in vivo.
AB  - Here, I discuss how RNAi screening can be used effectively to uncover gene
      function. Specifically, I discuss the types of high-throughput assays that can be
      done in Drosophila cells and in vivo, RNAi reagent design and available reagent
      collections, automated screen pipelines, analysis of screen results, and
      approaches to RNAi results verification. 

PMID- 24576620
TI  - T cell epitope mimicry between Sjogren's syndrome Antigen A (SSA)/Ro60 and oral,
      gut, skin and vaginal bacteria.
AB  - This study was undertaken to test the hypothesis that Sjogren's syndrome Antigen
      A (SSA)/Ro60-reactive T cells are activated by peptides originating from oral and
      gut bacteria. T cell hybridomas generated from HLA-DR3 transgenic mice recognized
      3 regions on Ro60, with core epitopes mapped to amino acids 228-238, 246-256 and
      371-381. BLAST analysis identified several mimicry peptides, originating from
      human oral, intestinal, skin and vaginal bacteria, as well as environmental
      bacteria. Amongst these, a peptide from the von Willebrand factor type A domain
      protein (vWFA) from the oral microbe Capnocytophaga ochracea was the most potent
      activator. Further, Ro60-reactive T cells were activated by recombinant vWFA
      protein and whole Escherichia coli expressing this protein. These results
      demonstrate that peptides derived from normal human microbiota can activate Ro60
      reactive T cells. Thus, immune responses to commensal microbiota and
      opportunistic pathogens should be explored as potential triggers for initiating
      autoimmunity in SLE and Sjogren's syndrome.

PMID- 24576623
TI  - Structural and cultural sources of community in American congregations.
AB  - Religious institutions are among the deepest reservoirs of social belonging in
      America, but what determines whether belonging is cultivated in these
      institutions? Previous research shows that individuals' social network
      composition is a primary predictor of feelings of belonging. However, less is
      known about how group characteristics condition the influence of social networks
      on belonging. We use data from the 2001 U.S. Congregational Life Survey and
      multilevel modeling to examine how organizational characteristics such as group
      size, in-group network density, and aggregate ideological uniformity moderate the
      effects of individual social networks on sense of belonging. Results indicate
      that both structural (network density, church size) and cultural (ideology)
      characteristics of groups significantly condition the effects of individual
      social networks on belonging. Smaller group size, network density, and
      ideological unity cultivate contexts that amplify the relationship between
      personal networks and belonging. 

PMID- 24576622
TI  - Differential outcome of MEK1/2 inhibitor-platinum combinations in platinum
      sensitive and -resistant ovarian carcinoma cells.
AB  - Deregulated pro-survival signalling plays a role in ovarian carcinoma drug
      resistance. Here, we show that cisplatin or oxaliplatin in combination with the
      MEK1/2 inhibitor CI-1040 resulted in a synergistic effect associated with
      enhanced apoptotic response in platinum-sensitive cells. The drug combinations
      were additive in platinum-resistant cells exhibiting increased phospho-ERK1/2,
      down-regulation of apoptosis-related factors (BAX, PUMA, FOXO1) and of
      phosphatases inhibiting ERK1/2 (DUSP5, DUSP6). Consistently, FOXO1 knockdown in
      sensitive cells reduced the efficacy of the combination treatment.
      Pharmacological targeting of ERK1/2 pathway increases cell sensitivity to
      platinum compounds by interfering with multiple events, ultimately favouring
      apoptosis induction in selected molecular backgrounds. 

PMID- 24576621
TI  - Combination PI3K/MEK inhibition promotes tumor apoptosis and regression in PIK3CA
      wild-type, KRAS mutant colorectal cancer.
AB  - PI3K inhibition in combination with other agents has not been studied in the
      context of PIK3CA wild-type, KRAS mutant cancer. In a screen of phospho-kinases,
      PI3K inhibition of KRAS mutant colorectal cancer cells activated the MAPK
      pathway. Combination PI3K/MEK inhibition with NVP-BKM120 and PD-0325901 induced
      tumor regression in a mouse model of PIK3CA wild-type, KRAS mutant colorectal
      cancer, which was mediated by inhibition of mTORC1, inhibition of MCL-1, and
      activation of BIM. These findings implicate mitochondrial-dependent apoptotic
      mechanisms as determinants for the efficacy of PI3K/MEK inhibition in the
      treatment of PIK3CA wild-type, KRAS mutant cancer. 

PMID- 24576624
TI  - How states can reduce the dropout rate for undocumented immigrant youth: the
      effects of in-state resident tuition policies.
AB  - As of December 2011, 13 states have adopted an in-state resident tuition (IRT)
      policy that provides in-state tuition to undocumented immigrants and several
      other states are considering similar legislation. While previous research focuses
      on how IRT policies affect college entry and attainment, this study examines the
      effect these policies have on high school dropout behavior. Using the Current
      Population Survey (CPS) and difference-in-difference models, this paper examines
      whether IRT policies reduce the likelihood of dropping out of high school for
      Mexican foreign-born non-citizens (FBNC), a proxy for undocumented youth. The
      policy is estimated to cause an eight percentage point reduction in the
      proportion that drops out of high school. The paper develops an integrated
      framework that combines human capital theory with segmented assimilation theory
      to provide insight into how IRT policies influence student motivation and
      educational attainment at the high school level. 

PMID- 24576625
TI  - Link between unemployment and crime in the US: a Markov-Switching approach.
AB  - This study has two goals. The first is to use Markov Switching models to identify
      and analyze the cycles in the unemployment rate and four different types of
      property-related criminal activities in the US. The second is to apply the
      nonparametric concordance index of Harding and Pagan (2006) to determine the
      correlation between the cycles of unemployment rate and property crimes. Findings
      show that there is a positive but insignificant relationship between the
      unemployment rate, burglary, larceny, and robbery. However, the unemployment rate
      has a significant and negative (i.e., a counter-cyclical) relationship with motor
      vehicle theft. Therefore, more motor-vehicle thefts occur during economic
      expansions relative to contractions. Next, we divide the sample into three
      different subsamples to examine the consistency of the findings. The results show
      that the co-movements between the unemployment rate and property crimes during
      recession periods are much weaker, when compared with that of the normal periods
      of the US economy. 

PMID- 24576626
TI  - Delinquent behavior, the transition to adulthood, and the likelihood of military
      enlistment.
AB  - Using data taken from the 1997 National Longitudinal Survey of Youth we examine
      the relationship between delinquency and enlistment in the military. We argue
      that delinquent behavior is positively related to enlistment because military
      service is an attractive alternative for delinquents to mark their transition to
      adulthood and their desistance from delinquent behavior. We also argue, however,
      that this relationship is not linear, with higher levels of delinquent behavior
      actually acting to reduce the likelihood of enlistment. We further suggest that
      the relationship between delinquency and enlistment is similar for men and women.
      We test and find support for our hypotheses using data taken from the 1997
      National Longitudinal Survey of Youth. 

PMID- 24576627
TI  - Collective pedagogical teacher culture, teacher-student ethno-racial mismatch,
      and teacher job satisfaction.
AB  - Teacher job satisfaction is critical to schools' successful functioning. Using a
      representative sample of kindergarten teachers from the Early Childhood
      Longitudinal Study, we investigate the association among professional learning
      community and teacher collaboration, teacher ethno-racial group, teacher-student
      ethno-racial mismatch, and teacher job satisfaction. We find that White teachers
      are significantly less satisfied than African-American and Latino teachers,
      especially when they teach in majority non-White classrooms. However, the
      existence of a professional community moderates the negative influence of teacher
      student ethno-racial mismatch on White teachers' job satisfaction. In effect,
      strong professional communities serve as a cushion to bolster teacher job
      satisfaction. 

PMID- 24576628
TI  - Modeling time-series count data: the unique challenges facing political
      communication studies.
AB  - This paper demonstrates the importance of proper model specification when
      analyzing time-series count data in political communication studies. It is common
      for scholars of media and politics to investigate counts of coverage of an issue
      as it evolves over time. Many scholars rightly consider the issues of time
      dependence and dynamic causality to be the most important when crafting a model.
      However, to ignore the count features of the outcome variable overlooks an
      important feature of the data. This is particularly the case when modeling data
      with a low number of counts. In this paper, we argue that the Poisson
      autoregressive model (Brandt and Williams, 2001) accurately meets the needs of
      many media studies. We replicate the analyses of Flemming et al. (1997), Peake
      and Eshbaugh-Soha (2008), and Ura (2009) and demonstrate that models missing some
      of the assumptions of the Poisson autoregressive model often yield invalid
      inferences. We also demonstrate that the effect of any of these models can be
      illustrated dynamically with estimates of uncertainty through a simulation
      procedure. The paper concludes with implications of these findings for the
      practical researcher. 

PMID- 24576629
TI  - Using population screening for recruitment of young adults engaged in illicit
      drug use: methodological issues and sampling outcomes.
AB  - Social stigma, legal sanctions and the associated lack of sampling frames create
      barriers to the probabilistic sampling of those engaged in a variety of
      behaviour, including illicit drug use. We used a novel sampling approach to
      recruit respondents into a longitudinal study examining amphetamine-type
      stimulant use. A young adult population was screened for lifetime drug use to
      create a sampling frame of amphetamine-type stimulant users and non-users. We
      posted 12,118 screening questionnaires to a random selection of young adults
      listed on the electoral roll for Brisbane and the Gold Coast, Australia
      (N=107,275). Using a small pre-paid incentive and intensive telephone and postal
      reminders we attained a screening response rate of 49.9%. Eligible amphetamine
      type stimulant users (used ecstasy or methamphetamine?3 times in past 12 months)
      and non-users (never used ecstasy or methamphetamine) were identified by
      screening responses. About two-thirds of each selected group took part in the
      longitudinal study. Comparisons with large-scale population survey data suggest
      the sample was broadly representative of young adult amphetamine-type stimulant
      users in Australia.

PMID- 24576630
TI  - Hierarchical Bayesian analysis of outcome- and process-based social preferences
      and beliefs in Dictator Games and sequential Prisoner's Dilemmas.
AB  - In this paper, using a within-subjects design, we estimate the utility weights
      that subjects attach to the outcome of their interaction partners in four
      decision situations: (1) binary Dictator Games (DG), second player's role in the
      sequential Prisoner's Dilemma (PD) after the first player (2) cooperated and (3)
      defected, and (4) first player's role in the sequential Prisoner's Dilemma game.
      We find that the average weights in these four decision situations have the
      following order: (1)>(2)>(4)>(3). Moreover, the average weight is positive in (1)
      but negative in (2), (3), and (4). Our findings indicate the existence of strong
      negative and small positive reciprocity for the average subject, but there is
      also high interpersonal variation in the weights in these four nodes. We conclude
      that the PD frame makes subjects more competitive than the DG frame. Using
      hierarchical Bayesian modeling, we simultaneously analyze beliefs of subjects
      about others' utility weights in the same four decision situations. We compare
      several alternative theoretical models on beliefs, e.g., rational beliefs
      (Bayesian-Nash equilibrium) and a consensus model. Our results on beliefs
      strongly support the consensus effect and refute rational beliefs: there is a
      strong relationship between own preferences and beliefs and this relationship is
      relatively stable across the four decision situations. 

PMID- 24576631
TI  - Identities in flux: cognitive network activation in times of change.
AB  - Using a dynamic cognitive model, we experimentally test two competing hypotheses
      that link identity and cognitive network activation during times of change. On
      one hand, affirming people's sense of power might give them confidence to think
      beyond the densest subsections of their social networks. Alternatively, if such
      power affirmations conflict with people's more stable status characteristics,
      this could create tension, deterring people from considering their networks'
      diversity. We test these competing hypotheses experimentally by priming people at
      varying levels of status with power (high/low) and asking them to report their
      social networks. We show that confirming identity-not affirming power-cognitively
      prepares people to broaden their social networks when the world is changing
      around them. The emotional signature of having a confirmed identity is feeling
      comfortable and in control, which mediates network activation. We suggest that
      stable, confirmed identities are the foundation from which people can exhibit
      greater network responsiveness. 

PMID- 24576632
TI  - Power-use in cooperative competition: a power-dependence model and an empirical
      test of network structure and geographic mobility.
AB  - Although the social exchange paradigm has produced a vibrant research program,
      the theoretical tradition is rarely used to model the structure of social
      networks outside of experiments and simulations. To address this limitation, we
      derive power-dependence predictions about network structure and geographic
      mobility-the outcomes of power-use-and test these predictions using complete data
      on competition networks and travel schedules among amateur sports teams. Poisson
      regression and exponential random graph models provide strong support for our
      predictions. The findings illustrate exchange dynamics in which status resources
      desired by teams, coupled with the availability of geographically proximal
      alternatives, create power and dependence that dictate where and with whom teams
      compete. Although evidence supports Georg Simmel's classic proposition that
      networks form on the basis of values and propinquity, we show that this complex
      dynamic is conditional on power and dependence. We conclude by discussing
      implications and directions for future research. 

PMID- 24576633
TI  - Pushed, pulled, or blocked? The elderly and the labor market in post-Soviet
      Russia.
AB  - Russia provides an interesting context for studying the labor market experiences
      of the elderly because of its experience with market transition, its looming
      growth in the elderly dependency ratio, and its unusual pension policies that do
      not penalize pensioners for working. We use data from twenty surveys of the
      Russian population conducted from February 1991 to November 2007 to analyze the
      labor market participation and earnings of elderly Russians following market
      transition. Economic desperation, exacerbated by low pension levels, pushed some
      elderly to seek employment for income on the labor market. Elderly Russians with
      more education had more opportunities to work, and education differentials
      increased as market reforms progressed. The correlates of earnings operate
      similarly for retirement- and pre-retirement age Russians, with several
      exceptions: unobserved factors favoring employment are negatively associated with
      earnings for the elderly, occupation mediates most of the effects of education,
      and patterns of change over time differ somewhat. Elderly Russians are not
      disproportionately blocked from employment following market reforms. Following
      the initial transition shock, their labor market activity increased. Overall,
      both push and pull factors shape the employment and earnings of the elderly,
      affecting different segments of them. 

PMID- 24576634
TI  - Residential hierarchy in Los Angeles: an examination of ethnic and documentation
      status differences.
AB  - Longitudinal event history data from two waves of the Los Angeles Family and
      Neighborhood Survey are used to explore racial, ethnic, and documentation status
      differences in access to desirable neighborhoods. We first find that contrary to
      recent findings, undocumented Latinos do not replace blacks at the bottom of the
      locational attainment hierarchy. Whites continue to end up in neighborhoods that
      are less poor and whiter than minority groups, while all minorities, including
      undocumented Latinos, end up in neighborhoods that are of similar quality.
      Second, the effects of socioeconomic status for undocumented Latinos are either
      similar to or weaker than disadvantaged blacks. These findings suggest that
      living in less desirable neighborhoods is a fate disproportionately borne by non
      white Los Angeles residents and that in some limited ways, the penalty attached
      to being undocumented Latino might actually be greater than the penalty attached
      to being black. 

PMID- 24576635
TI  - Personal traits, cohabitation, and marriage.
AB  - This study examines how personal traits affect the likelihood of entering into a
      cohabitating or marital relationship using a competing risk survival model with
      cohabitation and marriage as competing outcomes. The data are from Waves 1, 3,
      and 4 of the National Longitudinal Study of Adolescent Health, a rich dataset
      with a large sample of young adults (N=9835). A personal traits index is
      constructed from interviewer-assessed scores on the respondents' physical
      attractiveness, personality, and grooming. Having a higher score on the personal
      traits index is associated with a greater hazard of entering into a marital
      relationship for men and women, but the score does not have a significant
      influence on entering into a cohabitating relationship. Numerous sensitivity
      tests support the core findings. 

PMID- 24576637
TI  - You don't have to be well-educated to be an aversive racist, but it helps.
AB  - People with higher levels of formal education report less prejudice in survey
      research. Here we present novel evidence on the nature of educational differences
      in anti-Black attitudes among Whites. We replicate the education effect on
      explicit self-report measures of anti-Black attitudes, but we find that education
      is much less related to implicit measures of anti-Black attitudes. Implicit
      measures differ from explicit measures in that they do not allow respondents to
      control the measurement outcome; they therefore measure more spontaneous aspects
      of attitudes. These results shed new light on intergroup attitudes of the higher
      educated. Higher educated people are more likely to be aversive racists, that is,
      to score low on explicit, but not implicit measures of prejudice. Given the
      differential relation of explicit versus implicit measures to behavior, they have
      wide-ranging implications for the kind of intergroup behavior and discrimination
      we can expect from less and more highly educated people. 

PMID- 24576636
TI  - Beyond English proficiency: rethinking immigrant integration.
AB  - We develop and test a conceptual model of English language acquisition and the
      strength of the latter in predicting social and cultural assimilation. We present
      evidence that the path to English proficiency begins with exposure to English in
      the home country and on prior U.S. trips. English proficiency, then, has direct
      links to the intermediate migration outcomes of occupational status in the U.S.,
      the amount of time in the U.S. since the most recent trip, and the co-ethnic
      residential context in the U.S. In turn, pre-migration characteristics and the
      intermediate characteristics work in tandem with English proficiency to determine
      social assimilation in the U.S., while cultural assimilation is primarily
      determined by pre-migration habits. A shift in focus to English use is desirable
      in studies of immigrant integration. 

PMID- 24576638
TI  - How old are chimpanzee communities? Time to the most recent common ancestor of
      the Y-chromosome in highly patrilocal societies.
AB  - Many human societies are patrilineal, with males passing on their name or descent
      group affiliation to their offspring. Y-chromosomes are also passed on from
      father to son, leading to the simple expectation that males sharing the same
      surname or descent group membership should have similar Y-chromosome haplotypes.
      Although several studies in patrilineal human societies have examined the
      correspondence between Y-chromosome variation and surname or descent group
      membership, similar studies in non-human animals are lacking. Chimpanzees
      represent an excellent species for examining the relationship between descent
      group membership and Y-chromosome variation because they live in strongly male
      philopatric communities that arise by a group-fissioning process. Here we take
      advantage of recent analytical advances in the calculation of the time to the
      most recent common male ancestor and a large sample size of 273 Y-chromosome
      short tandem repeat haplotypes to inform our understanding of the potential ages
      of eight communities of chimpanzees. We find that the times to the most recent
      common male ancestor of chimpanzee communities are several hundred to as much as
      over two thousand years. These genetic estimates of the great time depths of
      chimpanzee communities accord well with behavioral observations suggesting that
      community fissions are a very rare event and are similar to genetic estimates of
      the time depth of patrilineal human groups. 

PMID- 24576640
TI  - Proteomics on porcine haptoglobin and IgG/IgA show protein species distribution
      and glycosylation pattern to remain similar in PCV2-SD infection.
AB  - Haptoglobin (Hp) and immunoglobulins are plasma glycoproteins involved in the
      immune reaction of the organism after infection and/or inflammation. Porcine
      circovirus type 2-systemic disease (PCV2-SD), formerly known as postweaning
      multisystemic wasting syndrome (PMWS), is a globally spread pig disease of great
      economic impact. PCV2-SD affects the immunological system of pigs causing
      immunosuppression. The aim of this work was to characterize the Hp protein
      species of healthy and PCV2-SD affected pigs, as well as the protein backbone and
      the glycan chain composition of porcine Hp. PCV2-SD affected pigs had an
      increased overall Hp level, but it did not affect the ratio between Hp species.
      Glycoproteomic analysis of the Hp beta subunits confirmed that porcine Hp is N
      glycosylated and, unexpectedly, O-glycosylated, a PTM that is not found on Hp
      from healthy humans. The glyco-profile of porcine IgG and IgA heavy chains was
      also characterized; decreased levels of both proteins were found in the
      investigated group of PCV2-SD affected pigs. Obtained results indicate that no
      significant changes in the N- and O-glycosylation patterns of these major porcine
      plasma glycoproteins were detectable between healthy and PCV2-SD affected
      animals. BIOLOGICAL SIGNIFICANCE: PCV2-SD is a disease of great economic
      importance for pig production, characterized by a complex response of the immune
      system. In the search of a better diagnostic/prognostic marker for porcine PCV2
      SD, extensive analyses of the Hp protein backbone and the glycan chains were
      thoroughly analyzed by various techniques. This resulted in detection and
      confirmation of Hp O-glycosylation and the glyco-profiling of porcine IgG and
      IgA. The N- and O-glycosylation of these major porcine plasma glycoproteins
      appears to be not affected by PCV2-SD infection. Interestingly, these data
      suggest that this viral infection, which significantly affects the immune
      responses of the host, leaves the biosynthetic glycosylation processes in the
      liver and immune cells unaffected. Lack of PTM changes is in contrast to findings
      in humans where for both proteins pattern changes have been reported in several
      chronic and inflammatory diseases. This underlines the importance of studying
      species in detail and not reaching to conclusions by analogy. Furthermore, since
      Hp is usually quantified by immunoassays in clinical routine analyses, our
      findings indicate that no bias in Hp determination capabilities due to an altered
      carbohydrate pattern is to be expected.

PMID- 24576642
TI  - Venomous snakes of Costa Rica: biological and medical implications of their venom
      proteomic profiles analyzed through the strategy of snake venomics.
AB  - In spite of its small territory of ~50,000km(2), Costa Rica harbors a remarkably
      rich biodiversity. Its herpetofauna includes 138 species of snakes, of which
      sixteen pit vipers (family Viperidae, subfamily Crotalinae), five coral snakes
      (family Elapidae, subfamily Elapinae), and one sea snake (Family Elapidae,
      subfamily Hydrophiinae) pose potential hazards to human and animal health. In
      recent years, knowledge on the composition of snake venoms has expanded
      dramatically thanks to the development of increasingly fast and sensitive
      analytical techniques in mass spectrometry and separation science applied to
      protein characterization. Among several analytical strategies to determine the
      overall protein/peptide composition of snake venoms, the methodology known as
      'snake venomics' has proven particularly well suited and informative, by
      providing not only a catalog of protein types/families present in a venom, but
      also a semi-quantitative estimation of their relative abundances. Through a
      collaborative research initiative between Instituto de Biomedicina de Valencia
      (IBV) and Instituto Clodomiro Picado (ICP), this strategy has been applied to the
      study of venoms of Costa Rican snakes, aiming to obtain a deeper knowledge on
      their composition, geographic and ontogenic variations, relationships to
      taxonomy, correlation with toxic activities, and discovery of novel components.
      The proteomic profiles of venoms from sixteen out of the 22 species within the
      Viperidae and Elapidae families found in Costa Rica have been reported so far,
      and an integrative view of these studies is hereby presented. In line with other
      venomic projects by research groups focusing on a wide variety of snakes around
      the world, these studies contribute to a deeper understanding of the biochemical
      basis for the diverse toxic profiles evolved by venomous snakes. In addition,
      these studies provide opportunities to identify novel molecules of potential
      pharmacological interest. Furthermore, the establishment of venom proteomic
      profiles offers a fundamental platform to assess the detailed immunorecognition
      of individual proteins/peptides by therapeutic or experimental antivenoms, an
      evolving methodology for which the term 'antivenomics' was coined (as described
      in an accompanying paper in this special issue). BIOLOGICAL SIGNIFICANCE: Venoms
      represent an adaptive trait and an example of both divergent and convergent
      evolution. A deep understanding of the composition of venoms and of the
      principles governing the evolution of venomous systems is of applied importance
      for exploring the enormous potential of venoms as sources of chemical and
      pharmacological novelty but also to fight the consequences of snakebite
      envenomings. Key to this is the identification of evolutionary and ecological
      trends at different taxonomical levels. However, the evolution of venomous
      species and their venoms do not always follow the same course, and the
      identification of structural and functional convergences and divergences among
      venoms is often unpredictable by a phylogenetic hypothesis. Snake venomics is a
      proteomic-centered strategy to deconstruct the complex molecular phenotypes the
      venom proteomes. The proteomic profiles of venoms from sixteen out of the 22
      venomous species within the Viperidae and Elapidae families found in Costa Rica
      have been completed so far. An integrative view of their venom composition,
      including the identification of geographic and ontogenic variations, is hereby
      presented. Venom proteomic profiles offer a fundamental platform to assess the
      detailed immunorecognition of individual venom components by therapeutic or
      experimental antivenoms. This aspect is reviewed in the companion paper. This
      article is part of a Special Issue entitled: Proteomics of non-model organisms.

PMID- 24576643
TI  - Management of fatigue in patients with cancer -- a practical overview.
AB  - Cancer-related fatigue (CRF) is a serious clinical problem and is one of the most
      common symptoms experienced by cancer patients. CRF has deleterious effects on
      many aspects of patient quality of life including their physical, psychological
      and social well-being. It can also limit their ability to function, socialise and
      participate in previously enjoyable activities. The aetiology of CRF is complex
      and multidimensional, involving many potentially contributing elements. These
      include tumour-related factors and comorbid medical/psychological conditions and
      also side effects associated with anti-cancer therapies or other medications.
      Barriers to the effective management of CRF exist both on the side of physicians
      and patients, and as a result CRF often remains unrecognised and undiscussed in
      clinical practice. A change of approach is required, where fatigue is treated as
      central to patient management during and after systemic anti-cancer treatment. In
      this review we summarise factors involved in the aetiology of CRF and the
      barriers to its effective management, as well as factors involved in the
      screening, diagnosis and treatment of cancer patients experiencing fatigue.
      Pharmacological and non-pharmacological approaches to its management are also
      reviewed. We suggest an algorithm for the process of managing CRF, guided by our
      experiences in The Netherlands, which we hope may provide a useful tool to
      healthcare professionals dealing with cancer patients in their daily practice.
      Although CRF is a serious and complex clinical problem, if it is worked through
      in a structured and comprehensive way, effective management has the potential to
      much improve patient quality of life. 

PMID- 24576641
TI  - Effect of hypoxia on lung gene expression and proteomic profile: insights into
      the pulmonary surfactant response.
AB  - Exposure of lung to hypoxia has been previously reported to be associated with
      significant alterations in the protein content of bronchoalveolar lavage (BAL)
      and lung tissue. In the present work we have used a proteomic approach to
      describe the changes in protein complement induced by moderate long-term hypoxia
      (rats exposed to 10% O2 for 72h) in BAL and lung tissue, with a special focus on
      the proteins associated with pulmonary surfactant, which could indicate
      adaptation of this system to limited oxygen availability. The analysis of the
      general proteomic profile indicates a hypoxia-induced increase in proteins
      associated with inflammation both in lavage and lung tissue. Analysis at mRNA and
      protein levels revealed no significant changes induced by hypoxia on the content
      in surfactant proteins or their apparent oligomeric state. In contrast, we
      detected a hypoxia-induced significant increase in the expression and
      accumulation of hemoglobin in lung tissue, at both mRNA and protein levels, as
      well as an accumulation of hemoglobin both in BAL and associated with surface
      active membranes of the pulmonary surfactant complex. Evaluation of pulmonary
      surfactant surface activity from hypoxic rats showed no alterations in its
      spreading ability, ruling out inhibition by increased levels of serum or
      inflammatory proteins. BIOLOGICAL SIGNIFICANCE: This work reveals that hypoxia
      induces extensive changes in the proteomic profile of lung bronchoalveolar
      lavage, including the presence of proteins related with inflammation both in lung
      tissue and lavage, and a significant increase in the synthesis and secretion by
      the lung tissue of different forms of hemoglobin. The level of specific pulmonary
      surfactant-associated proteins is not substantially altered due to hypoxia, but
      hypoxia-adapted surfactant exhibits an enhanced ability to form surface-active
      films at the air-liquid interface. The increased amount of beta-globin integrated
      into the operative surfactant complexes obtained from hypoxic rats is a relevant
      feature that points to the existence of adaptive responses coupling surfactant
      function and oxygen availability.

PMID- 24576644
TI  - Post-catheterisation arterial thrombosis in children--pathophysiology,
      prevention, and treatment.
AB  - Lower limb ischaemia is the most frequent complication of cardiac catheterisation
      in children. It is often overlooked, but it can cause significant disability and
      may limit arterial access sites to repeat diagnostic or interventional
      catheterisations. A narrative review of the literature on arterial access site
      thrombosis in children was carried out with a special focus on current evidence
      that supports preventive and treatment strategies. Anticoagulation, thrombolysis,
      and thrombectomy have been used successfully to treat arterial access site
      thrombosis. However, it is not completely established which is the role of each
      treatment modality and what is the most appropriate timing to deliver it.
      Therefore, diagnostic and therapeutic strategies have to be prospectively
      investigated, particularly for clarifying the role of new pharmacologic
      interventions and of percutaneous and surgical thrombectomy in the current era. 

PMID- 24576645
TI  - The potential consequences of informal interpreting practices for assessment of
      patients in a South African psychiatric hospital.
AB  - In South Africa health care practitioners are commonly professionals who speak
      only one, or at most two, of the languages spoken by their patients. This
      provides for language provision challenges, since many patients are not
      proficient in English or Afrikaans and ad hoc and haphazard arrangements are made
      for interpreting by untrained personnel. As part of a larger study (conducted in
      2010) in a public psychiatric hospital, we report here on the potential
      consequences for diagnostic assessments of 13 psychiatric evaluations mediated by
      ad hoc interpreters who were employed as health care workers and household aides.
      The psychiatric evaluations were recorded and transcribed verbatim. The first
      author checked for accuracy of transcription and translations, and the two
      members of the author team who are both senior African language academics
      rechecked transcription and translation. We used the typology developed by
      Vasquez and Javier (1991) to study interpreter errors (i.e. omissions, additions
      and substitutions). All errors were independently rated by a senior psychiatrist
      and a senior clinical psychologist to determine whether the errors were likely to
      have a bearing on clinical decisions concerning the patient and to rate whether
      errors deemed clinically significant contributed to making the patient appear
      more ill psychiatrically, or less ill. Of the 57 errors recorded, 46% were rated
      as likely to have an impact on the goal of the clinical session. Raters concurred
      that the clinically significant errors contributed towards potentially making the
      patient look more psychiatrically ill. Detailed analyses of evaluations
      demonstrate the complexity of informal interpreter positioning regarding issues
      of diagnosis and cultural factors in illness. Evaluations conducted where
      clinicians and interpreters are not trained in language and interpreting issues
      may create a distorted picture of the patients' mental health conditions. 

PMID- 24576646
TI  - Women's empowerment and generalized anxiety in Minya, Egypt.
AB  - Gender disparities in mental health are global, with women experiencing higher
      rates than men of anxiety disorders, mood disorders, and attempted suicide.
      Women's low social status may partly explain these disparities, yet evidence from
      Arab and Middle Eastern settings is limited. We assessed whether women's
      empowerment - or acquisition of enabling resources, and in turn, enhanced agency 
      was associated with their lower generalized anxiety. For 539 ever-married women
      22-65 years who participated in the 2005 Egypt Demographic Health Survey (EDHS)
      and a 2012 follow-up survey in rural Minya, we estimated linear reduced-form and
      mediation regression models to assess the associations of women's premarital
      enabling resources with their generalized anxiety in 2012, overall and through
      measures of their marital agency in 2005. Women's higher schooling attainment,
      premarital economic activity, later age at first marriage, and greater proximity
      to natal (or birth) family had significant, adjusted associations with lower
      generalized anxiety. Measures of women's agency in marriage had mixed
      associations with generalized anxiety, but their inclusion modestly reduced the
      coefficients for premarital resources. Parallel qualitative findings confirmed
      nuanced associations between women's exclusive decision-making and their mental
      health. Efforts to enhance women's education and premarital economic activity
      might be combined with efforts to delay first marriage and ensure women's extra
      marital social support to maximize their empowerment and its mental-health
      benefits. 

PMID- 24576647
TI  - Barriers in access to healthcare in countries with different health systems. A
      cross-sectional study in municipalities of central Colombia and north-eastern
      Brazil.
AB  - There are few comprehensive studies available on barriers encountered from the
      initial seeking of healthcare through to the resolution of the health problem; in
      other words, on access in its broad domain. For Colombia and Brazil, countries
      with different healthcare systems but common stated principles, there have been
      no such analyses to date. This paper compares factors that influence access in
      its broad domain in two municipalities of each country, by means of a cross
      sectional study based on a survey of a multistage probability sample of people
      who had had at least one health problem within the last three months (2163 in
      Colombia and 2155 in Brazil). The results reveal important barriers to healthcare
      access in both samples, with notable differences between and within countries,
      once differences in sociodemographic characteristics and health needs are
      accounted for. In the Colombian study areas, the greatest barriers were
      encountered in initial access to healthcare and in resolving the problem, and
      similarly when entering the health service in the Brazilian study areas.
      Differences can also be detected in the use of services: in Colombia greater
      geographical and economic barriers and the need for authorization from insurers
      are more relevant, whereas in Brazil, it is the limited availability of health
      centres, doctors and drugs that leads to longer waiting times. There are also
      differences according to enrolment status and insurance scheme in Colombia, and
      between areas in Brazil. The barriers appear to be related to the Colombian
      system's segmented, non-universal nature, and to the involvement of insurance
      companies, and to chronic underfunding of the public system in Brazil. Further
      research is required, but the results obtained reveal critical points to be
      tackled by health policies in both countries. 

PMID- 24576648
TI  - Collective levels of stigma and national suicide rates in 25 European countries.
AB  - AIMS: There is substantial diversity in national suicide rates, which has mainly
      been related to socio-economic factors, as well as cultural factors. Stigma is a
      cultural phenomenon, determining the level of social acceptance or rejection of
      persons with mental illness in a society. In this study, we explore whether
      national suicide rates are related to the degree of mental illness stigma in that
      country. METHODS: We combine the data on country-level social acceptance
      (Eurobarometer) with the data on suicide rates and socio-economic indicators
      (Eurostat) for 25 European countries. RESULTS: In a linear regression model
      controlling for socio-economic indicators, the social acceptance of someone with
      a significant mental health problem in 2010 was negatively correlated with age
      standardised national suicide rates in the same year (beta -0.46, p = 0.014).
      This association also held true when combining national suicide rates with death
      rates due to events of undetermined intent. CONCLUSIONS: Stigma towards persons
      with mental health problems may contribute to differences in suicide rates in a
      country. We hypothesise possible mechanisms explaining this link, including
      stigma as a stressor and social isolation as a consequence of stigma.

PMID- 24576649
TI  - Measurement of the crystalline lens radius with artemis very high frequency
      ultrasound biomicroscopy for implantable collamer lens sizing.

PMID- 24576650
TI  - Enhanced ectasia screening: the need for advanced and objective data.

PMID- 24576651
TI  - Longitudinal postoperative lasik epithelial thickness profile changes in
      correlation with degree of myopia correction.
AB  - PURPOSE: To evaluate epithelial thickness profile changes following myopic
      femtosecond laser-assisted LASIK in relation to the degree of myopia corrected,
      evaluated with a spectral-domain anterior-segment optical coherence tomography
      system. METHODS: Sixty-one consecutive cases were observed for corneal epithelial
      thickness distribution preoperatively and at 1 day, 1 week, 1 month, and 1 year
      postoperatively. Epithelial thickness mapping was obtained with a spectral-domain
      optical coherence tomography system (Optovue Inc., Fremont, CA). Descriptive
      statistics investigated epithelial thickness at the central 2-mm area, the mean
      over the central 6-mm area, and mid-peripherally at the 5-mm ring area. RESULTS:
      Preoperatively, the pupil center epithelial thickness was 51.67 +/- 2.57 MUm
      (range: 45 to 56 MUm), mean was 51.76 +/- 2.66 MUm (range: 45 to 57 MUm), and mid
      periphery was 51.78 +/- 2.71 MUm (range: 46 to 57 MUm). Compared to the
      preoperative values, the epithelial thickness for the center, mean, and mid
      periphery was -0.30, +1.07, and +1.35 MUm at 1 week, +1.58, +2.88, and +3.31 MUm
      at 1 month (P = .0036, < .001, and < .001), and +1.42, +2.90, and +3.19 MUm at 1
      year postoperatively (P = 0.146, < .001, and < .001), respectively. The
      correlation analysis between the epithelial thickness increase and the spherical
      equivalent of myopic correction showed a trend toward epithelial thickness
      increase with the amount of myopic ablation, particularly at the mid-peripheral 5
      mm area. CONCLUSIONS: In this comprehensive study of postoperative corneal
      epithelial thickness remodeling following femtosecond laser-assisted myopic LASIK
      correction, an increase at the 1-month and up to 1-year postoperative interval
      suggested postoperative epithelial activity in connection to the extent of
      ablation.

PMID- 24576652
TI  - Emission inventory of primary air pollutants in 2010 from industrial processes in
      Turkey.
AB  - The broad objective of this study was to develop CO2, PM, SOx, CO, NOx, VOC, NH3
      and N2O emission inventory of organic and inorganic chemicals, mineral products,
      metallurgical, petroleum refining, wood products, food industries of Turkey for
      2010 for both co]ntrolled and uncontrolled conditions. In this study, industries
      were investigated in 7 main categories and 53 sub-sectors and a representative
      number of pollutants per sub-sector were considered. Each industry was evaluated
      in terms of emitted emissions only from industrial processes, and fuel combustion
      activities were excluded (except cement industry). The study employed an approach
      designed in four stages; identification of key categories; activity data &
      emission factor search; emission factor analyzing; calculation of emissions.
      Emission factor analyzing required aggregate and firm analysis of sectors and sub
      sectors and deeper insights into underlying specific production methods used in
      the industry to decide on the most representative emission factor. Industry
      specific abatement technologies were considered by using open-source documents
      and industry specific reports. Regarding results of this study, mineral industry
      and iron & steel industry were determined as important contributors of industrial
      emissions in Turkey in 2010. Respectively, organic chemicals, petroleum refining,
      and pulp & paper industries had serious contributions to Turkey's air pollutant
      emission inventory from industrial processes. The results showed that calculated
      CO2 emissions for year 2010 was 55,124,263 t, also other emissions were 48,853 t
      PM, 24,533 t SOx, 79,943 t NOx, 31,908 t VOC, 454 t NH3 and 2264 t N2O under
      controlled conditions.

PMID- 24576653
TI  - Coaxiality of Foxb1- and parvalbumin-expressing neurons in the lateral
      hypothalamic PV1-nucleus.
AB  - In the ventrolateral hypothalamus, the PV1-nucleus is defined by its population
      of parvalbumin-expressing neurons. During embryogenesis, the ventrolateral
      hypothalamus is colonized also by Foxb1-expressing neurons. In adult Foxb1-EGFP
      mice, many immunofluorescent neurons were found within the region that is
      occupied by the PV1-nucleus. They formed a cloud around the axial cord of the
      parvalbumin-immunopositive cells, which they greatly outnumber (3:1). Only a
      small proportion of the neurons in the PV1-nucleus co-expressed both parvalbumin
      and Foxb1. In the light of these findings, a redesignation of this lateral
      hypothalamic structure as the PV1-Foxb1 nucleus would more accurately reflect its
      specific biochemical properties. 

PMID- 24576654
TI  - Management of sorafenib-related adverse events: a clinician's perspective.
AB  - Sorafenib, a tyrosine kinase inhibitor, is approved for the treatment of patients
      with unresectable hepatocellular carcinoma (HCC) and advanced renal cell
      carcinoma (RCC). It is being evaluated in phase II and III clinical trials, which
      include treatment as a single agent (locally advanced/metastatic radioactive
      iodine-refractory differentiated thyroid cancer [DTC]), as part of multimodality
      care (HCC), and in combination with chemotherapeutic agents (metastatic breast
      cancer). Sorafenib-related adverse events (AEs) that commonly occur across these
      tumor types include hand-foot skin reaction (HSFR), rash, upper and lower
      gastrointestinal (GI) distress (ie, diarrhea), fatigue, and hypertension. These
      commonly range from grade 1 to 3, per the Common Terminology Criteria for Adverse
      Events (CTCAE), and often occur early in treatment. The goal for the management
      of these AEs is to prevent, treat, and/or minimize their effects, thereby
      enabling patients to remain on treatment and improve their quality of life.
      Proactive management, along with ongoing patient education (before and during
      sorafenib treatment), can help to effectively manage symptoms, often without the
      need for sorafenib dose modification or drug holidays. Effective management
      techniques for common sorafenib-related AEs, as well other important disease
      sequelae not directly related to treatment, are presented. Recommendations and
      observations are based on physician/author experience and recommendations from
      published literature. 

PMID- 24576655
TI  - Management of common adverse events in patients treated with sorafenib: nurse and
      pharmacist perspective.
AB  - Sorafenib, a tyrosine kinase inhibitor, is indicated for the treatment of
      patients with unresectable hepatocellular carcinoma (HCC) and advanced renal cell
      carcinoma (RCC). Sorafenib is currently being evaluated in phase II and III
      trials in various malignancies as a single agent (locally advanced/metastatic
      radioactive iodine-refractory differentiated thyroid cancer [DTC]), as part of
      multimodality care (HCC), and in combination with chemotherapies (metastatic
      breast cancer). Grade 1 and 2 adverse events (AEs) that commonly occur during
      treatment (ie, dermatologic manifestations, diarrhea, fatigue, and hypertension)
      should be proactively managed. The goal is to allow patients to remain on their
      full dose of sorafenib for as long as their treatment is indicated. A combination
      of early recognition of and intervention for AEs, patient education, and an open
      dialogue between patients and their multidisciplinary healthcare team, with
      timely reporting of AEs, will allow for effective management of AEs and minimize
      the need for sorafenib dose reduction or discontinuation. 

PMID- 24576656
TI  - The dramatic increase in social media in urology.
AB  - PURPOSE: Social media are established tools for rapid information dissemination
      to a broad audience. A major use has been the compilation of conference specific
      messaging known as tweets via preselected hashtags on Twitter. We analyzed
      Twitter use between consecutive years at the AUA (American Urological
      Association) and CUA (Canadian Urological Association) annual meetings. MATERIALS
      AND METHODS: Publicly available tweets containing the established meeting
      hashtags were abstracted from an online archive. Tweets were categorized by
      author type and by content as informative (based on research presented at the
      conference) or uninformative (unrelated to presented data) according to an
      established classification scheme. RESULTS: We analyzed 5,402 tweets during the
      combined 18 meeting days, of which 4,098 were original and 1,304 were rebroadcast
      prior tweets. There was a large increase in Twitter use at the 2013 annual
      meetings compared to the 2012 meetings (4,591 tweets from a total of 540 accounts
      vs 811 from 134). Biotechnology analysts represented the highest volume of tweets
      (226 or 28%) in 2012 but in 2013 this majority shifted to urologists (2,765 or
      60%). Of the tweets 29% were categorized as informative in 2012, which increased
      to 41% at the 2013 meetings. CONCLUSIONS: Twitter has emerged as a significant
      communication platform at urological meetings. Use increased dramatically between
      2012 and 2013. Urologists have increasingly led this discussion with an increased
      focus on data arising from meeting proceedings. This adjunct to traditional
      meeting activity merits the attention of urologists and the professional
      associations that host such meetings.

PMID- 24576657
TI  - Elucidation of distinctive genomic DNA structures in patients with 46,XX
      testicular disorders of sex development using genome wide analyses.
AB  - PURPOSE: Although several genes, including the SRY gene, are involved in
      testicular differentiation, the entire mechanism of this differentiation remains
      unclear. We performed genome wide analysis in patients with 46,XX testicular
      disorders of sex development to comprehensively elucidate the mechanisms of
      testicular differentiation. MATERIALS AND METHODS: Whole genomic DNA was
      extracted from the peripheral blood of 4 patients with 46,XX testicular disorders
      of sex development who were SRY negative. Genomic DNA was hybridized to a
      GeneChip(r) human mapping 250K array set. Compared to normal female data, we
      detected common loss of heterozygosity and copy number variation regions in 4
      patients using Genotyping ConsoleTM software. RESULTS: Loss of heterozygosity was
      detected in 19 regions of 11 chromosomes. A total of 27 genes or nearby genomic
      areas were included in the applicable regions. Copy number loss was recognized in
      13 regions of 10 chromosomes, and these regions included 55 genes. Copy number
      gain was detected in 6 regions of 4 chromosomes, which included the upstream
      region of the SOX3 gene. CONCLUSIONS: The regions with loss of heterozygosity did
      not contain genes associated with testicular differentiation. However, the
      upstream area of the SOX3 gene, which is located in Xq27.1, was included in the
      region of copy number gain. These results suggest that high expression of the
      SOX3 gene led to testicular differentiation despite SRY gene loss. As this
      applicable area is not within a coding region, genome wide analyses were valuable
      for detecting the novel regions associated with testicular differentiation.

PMID- 24576658
TI  - shRNA constructs targeting IGFBP-3 alleviate age related erectile dysfunction in
      the rat.
AB  - PURPOSE: We investigated whether injecting shRNA constructs targeting IGFBP-3 in
      the penis of old rats would improve erectile function. MATERIALS AND METHODS: The
      most validated IGFBP-3 shRNA plasmid vector (pGPU6/GFP/Neo-shIGFBP-3) was
      prepared and injected in penile corpus cavernosum tissue. A total of 30 old (age
      24 months) male Sprague Dawley(r) rats were randomly divided into 3 groups,
      including 10 each that received phosphate buffered saline only (100 MUl),
      pGPU6/GFP/Neo-shNC (100 MUg) and the most validated plasmid constructs
      pGPU6/GFP/Neo-shIGFBP-3 (100 MUg). At 4 weeks the erectile response was measured
      as intracavernous pressure. The percent of smooth muscle in corpus cavernosum
      tissue was evaluated. Nitric oxide synthase activity and the cGMP concentration
      in penile tissue were also analyzed. IGFBP-3 was estimated in penile tissue by
      Western blot, real-time reverse transcriptase-polymerase chain reaction and
      immunohistochemistry. RESULTS: pGPU6/GFP/Neo-shIGFBP-3 corrected the impaired
      erectile response in aged rats compared with the response in those injected with
      phosphate buffered saline and pGPU6/GFP/Neo-shNC (each p <0.01). The percent of
      cavernous smooth muscle was increased in the pGPU6/GFP/Neo-shIGFBP-3 group.
      Nitric oxide synthase activity and the cGMP concentration were also significantly
      increased in rats treated with pGPU6/GFP/Neo-shIGFBP-3. IGFBP-3 shRNA effectively
      reduced IGFBP-3 mRNA and protein expression in penile corpus cavernosum tissue.
      CONCLUSIONS: Decreasing IGFBP-3 expression by plasmid expressed shRNA improved
      erectile function in aged rats. The therapy may modulate smooth muscle integrity
      and increase the cGMP concentration. This may be a new direction for treating
      erectile dysfunction in clinical practice.

PMID- 24576659
TI  - Expression, purification and activity assay of a patchoulol synthase cDNA variant
      fused to thioredoxin in Escherichia coli.
AB  - Probing a cDNA library extracted from Pogostemon cablin (Indian Patchouli) with
      gene specific primers, a variant of patchoulol synthase PTS (GenBank acc. No.:
      AY508730) was amplified, cloned, and sequenced. The amino acid sequence deduced
      from the cloned cDNA exhibited a sequence variation of 3.4% compared to the
      annotated sequence. The enzyme variant tended to form inclusion bodies when
      expressed in Escherichia coli. The coding sequence was fused to the T7-tag, His
      tag and to thioredoxin. Constructs were expressed in three different E. coli
      expression strains, with several strain/construct combinations yielding soluble
      enzyme. By fusion to thioredoxin and careful codon optimization of the eukaryotic
      sequence, soluble expression could be improved on average by 42% in comparison to
      an unoptimized, His-tagged construct. The thioredoxin-fused protein was
      successfully purified using a one-step Co(2+)-IMAC purification procedure.
      Bioactivity assays using prepared farnesyl diphosphate (FDP) in milliliter-scale
      batch reactions, showed activity of the fused enzyme even with thioredoxin
      attached. The product spectrum of the enzyme was compared to patchouli oil
      standards by GC-MS and the main products were identified. Interestingly, the
      variant showed a shift in product spectrum with germacrene A being the most
      abundant product instead of patchouli alcohol. In silico structural modeling
      shows a possible chemical and structural change in the active site of the enzyme,
      which might be responsible for the shift in product composition. 

PMID- 24576662
TI  - Abstracts of the SIR 2014 Annual Scientific Meeting Program Convergence, 22-27
      March 2014, San Diego, CA.

PMID- 24576661
TI  - Enhanced expression and purification of inositol 1,4,5-trisphosphate 3-kinase A
      through use of the pCold1-GST vector and a C-terminal hexahistidine tag in
      Escherichia coli.
AB  - Inositol 1,4,5-trisphosphate 3-kinase A (IP3K-A, alternative name: ITPKA) is a
      neuron-specific enzyme that converts 1,4,5-trisphosphate (IP3) into inositol
      1,3,4,5-tetrakisphosphate (IP4) through its kinase domain. In addition, transient
      overexpression of IP3K-A induces morphological changes in dendritic spines of
      excitatory synapses in a kinase-independent manner, apparently by modulating the
      organization of the neuronal cytoskeleton. Although the procurement of a purified
      recombinant IP3K-A protein would be indispensable for the biochemical elucidation
      of its physiological roles, production of recombinant IP3K-A has proven
      technically challenging in conventional Escherichia coli expression systems.
      These difficulties stem from low enzyme solubility, as well as poor protein
      quality caused by the tendency of IP3K-A to split into partial fragments. In
      present study, we newly introduced cold-shock expression vector (pCold1) together
      with a C-terminal hexahistidine tag (C-HIS) to enhance the expression levels of
      recombinant IP3K-A in E. coli. Importantly, when compared with other commonly
      employed bacterial expression systems, the pCold1 system improved the yield and
      the purity of full-length IP3K-A due to the exclusion of truncated enzyme forms,
      and also enhanced the solubility of the enzyme. Furthermore, the functional
      integrity of purified IP3K-A was confirmed in both kinase activity assay and
      microtubule binding assay. Recombinant IP3K-A acquired via this modified protocol
      will be expected to facilitate the exploration of the enzyme's biochemical
      profile, both structurally and functionally. 

PMID- 24576660
TI  - Expression, purification, and characterization of mouse glycine N-acyltransferase
      in Escherichia coli.
AB  - Glycine N-acyltransferase (GLYAT) is a phase II metabolic detoxification enzyme
      for exogenous (xenobiotic) and endogenous carboxylic acids; consisting of fatty
      acids, benzoic acid, and salicylic acid. GLYAT catalyzes the formation of
      hippurate (N-benzoylglycine) from the corresponding glycine and benzoyl-CoA.
      Herein, we report the successful expression, purification, and characterization
      of recombinant mouse GLYAT (mGLYAT). A 34kDa mGLYAT protein was expressed in
      Escherichia coli and purified to homogeneity by nickel affinity chromatography to
      a final yield of 2.5mg/L culture. Characterization for both amino donors and
      amino acceptors were completed, with glycine serving as the best amino donor
      substrate, (kcat/Km)app=(5.2+/-0.20)*10(2)M(-1)s(-1), and benzoyl-CoA serving as
      the best the amino acceptor substrate, (kcat/Km)app=(4.5+/-0.27)*10(5)M(-1)s(-1).
      Our data demonstrate that mGLYAT will catalyzed the chain length specific (C2-C6)
      formation of N-acylglycines. The steady-state kinetic constants determined for
      recombinant mGLYAT for the substrates benzoyl-CoA and glycine, were shown to be
      consistent with other reported species (rat, human, bovine, ovine, and rhesus
      monkey). The successful recombinant expression and purification of mGLYAT can
      lead to solve unanswered questions associated with this enzyme, consisting of
      what is the chemical mechanism and what catalytic residues are essential for the
      how this phase II metabolic detoxification enzyme conjugates glycine to
      xenobiotic and endogenous carboxylic acids. 

PMID- 24576663
TI  - Synthesis and characterization of Schiff's bases of sulfamethoxazole.
AB  - BACKGROUND: Schiff's bases are excellent ligands which are synthesized from the
      condensation of primary amines with carbonyl groups. FINDINGS: The classical
      reaction for the synthesis of Schiff's bases in an ethanolic solution and glacial
      acetic acid as a catalyst was followed in the synthesis of substituted
      sulfamethoxazole compounds. CONCLUSIONS: Some Schiff's bases containing
      sulfamethoxazole nucleus have been synthesized and characterized. The present
      compounds are hoped to be applied in the photostability of PVC.

PMID- 24576664
TI  - A systematic review of noncommunicable health issues in mass gatherings.
AB  - INTRODUCTION: The review was conducted to evaluate if the field of mass-gathering
      medicine has evolved in addressing: (1) the lack of uniform standard measures;
      (2) the effectiveness of and needs for various interventions during a mass
      gathering; and (3) the various types of noncommunicable health issues (trauma and
      medical complaints) encountered and their severity during a gathering. METHODS: A
      systematic review of papers published from 2003 through 2012 was conducted using
      databases of MEDLINE, Ovid, CINHAL, EBSCOHost, National Library of Medicine
      (NLM), Agency for Healthcare Research and Quality (AHRQ), Elsevier, Scopus, and
      Proquest databases. Of 37,762 articles, 17 articles were included in this review,
      covering 18 mass-gathering events; 14 were multiple-day events. RESULTS: Across
      all events, the patient presentation rate (PPR) ranged from 0.13 to 20.8 patients
      per 1,000 attendees and the transfer to hospital rate (TTHR) ranged from 0.01 to
      10.2 ambulance transports per 1,000 attendees. In four out of the seven studies,
      having on-site providers was associated with a lower rate of ambulance
      transports. The highest frequencies of noncommunicable presentations were
      headaches, abdominal complaints, and abrasions/lacerations. Most presentations
      were minor. Emergent cases requiring hospitalization (such as acute myocardial
      infarction) were rare. CONCLUSIONS: The rate of noncommunicable health issues
      varies across events and very serious emergencies are rare.

PMID- 24576666
TI  - Impulsivity: four ways five factors are not basic to addiction.
AB  - Several impulsivity-related models have been applied to understanding the
      vulnerability to addiction. While there is a growing consensus that impulsivity
      is multifaceted, debate continues as to the precise number of facets and, more
      critically, which are most relevant to explaining the addiction-risk profile. In
      many ways, the current debate mirrors that which took place in the personality
      literature in the early 1990s (e.g., Eysenck's 'Big Three' versus Costa and
      McCrae's 'Big Five'). Indeed, many elements of this debate are relevant to the
      current discussion of the role of impulsivity in addictive behavior.
      Specifically, 1) the use of factor analysis as an atheoretical 'truth-grinding
      machine'; 2) whether additional facets add explanatory power over fewer; 3) the
      delineation of specific neurocognitive pathways from each facet to addictive
      behaviors, and; 4) the relative merit of 'top-down' versus 'bottom-up' approaches
      to the understanding of impulsivity. Ultimately, the utility of any model of
      impulsivity and addiction lies in its heuristic value and ability to integrate
      evidence from different levels of analysis. Here, we make the case that
      theoretically-driven, bottom-up models proposing two factors deliver the optimal
      balance of explanatory power, parsimony, and integration of evidence. 

PMID- 24576665
TI  - Histone deacetylase 6 inhibition improves memory and reduces total tau levels in
      a mouse model of tau deposition.
AB  - INTRODUCTION: Tau pathology is associated with a number of age-related
      neurodegenerative disorders. Few treatments have been demonstrated to diminish
      the impact of tau pathology in mouse models and none are yet effective in humans.
      Histone deacetylase 6 (HDAC6) is an enzyme that removes acetyl groups from
      cytoplasmic proteins, rather than nuclear histones. Its substrates include
      tubulin, heat shock protein 90 and cortactin. Tubastatin A is a selective
      inhibitor of HDAC6. Modification of tau pathology by specific inhibition of HDAC6
      presents a potential therapeutic approach in tauopathy. METHODS: We treated
      rTg4510 mouse models of tau deposition and non-transgenic mice with tubastatin
      (25 mg/kg) or saline (0.9%) from 5 to 7 months of age. Cognitive behavior
      analysis, histology and biochemical analysis were applied to access the effect of
      tubastatin on memory, tau pathology and neurodegeneration (hippocampal volume).
      RESULTS: We present data showing that tubastatin restored memory function in
      rTg4510 mice and reversed a hyperactivity phenotype. We further found that
      tubastatin reduced the levels of total tau, both histologically and by western
      analysis. Reduction in total tau levels was positively correlated with memory
      improvement in these mice. However, there was no impact on phosphorylated forms
      of tau, either by histology or western analysis, nor was there an impact on
      silver positive inclusions histologically. CONCLUSION: Potential mechanisms by
      which HDAC6 inhibitors might benefit the rTg4510 mouse include stabilization of
      microtubules secondary to increased tubulin acetylation, increased degradation of
      tau secondary to increased acetylation of HSP90 or both. These data support the
      use of HDAC6 inhibitors as potential therapeutic agents against tau pathology.

PMID- 24576669
TI  - Anomalous origin of the left subclavian artery from the pulmonary artery.
AB  - Isolated left subclavian artery from the pulmonary trunk is a rare congenital
      cardiovascular malformation. In this report, we present the images of ascending
      aortic aneurysm and left subclavian artery originating from the pulmonary artery
      in a 4-year-old girl in addition to her congenital cardiac pathology. 

PMID- 24576667
TI  - Hypoxia controls Flvcr1 gene expression in Caco2 cells through HIF2alpha and
      ETS1.
AB  - The tissue-specific gene expression changes mediated by the hypoxia inducible
      factors (HIFs) allow the adaptation of cells to low oxygen tension and control
      several processes including erythropoiesis, angiogenesis and vasculogenesis. The
      Feline Leukemia Virus, subgroup C, Receptor 1 (Flvcr1) gene encodes for two
      isoforms, Flvcr1a and 1b, involved in the export of heme out of the cell and of
      mitochondria respectively. Studies in mouse models demonstrated a crucial role of
      Flvcr1 isoforms in erythropoiesis and during embryo development. Here, we showed
      the modulation of Flvcr1 gene expression in different tissues and cell lines in
      response to hypoxia. Chromatin immunoprecipitation analysis demonstrated that
      HIF2alpha and HIF-dependent transcription factor ETS1 (v-ets avian
      erythroblastosis virus E26 oncogene homolog 1) bind at the region -318/+39 of the
      Flvcr1 promoter. Analysis of Caco2 cells in which HIF2alpha or ETS1 were silenced
      or overexpressed demonstrated that, both HIF2alpha and ETS1 are involved in the
      transcriptional regulation of Flvcr1a and that HIF2alpha is absolutely required
      for Flvcr1a induction upon hypoxia. The inclusion of the Flvcr1 gene in the group
      of HIF2alpha-responsive genes strengthens its role in hypoxia-stimulated
      processes like erythropoiesis, vasculogenesis and heme absorption.

PMID- 24576670
TI  - Public investment does not crowd out private supply of environmental goods on
      private land.
AB  - In landscapes where private land tenure is prevalent, public funds for ecological
      landscape restoration are sometimes spent subsidising the revegetation of cleared
      land, and the protection of remnant vegetation from livestock. However, the total
      area treated may be unclear because such projects are not always recorded, and
      landholders may undertake similar activities without subsidisation. In the
      absence of empirical data, in the state of Victoria, Australia, a reporting
      assumption has been employed that suggests that wholly privately funded sites
      match publicly subsidised sites on a hectare for hectare basis (a so-called "x2"
      assumption). Conversely, the "crowding out" theory of investment in public goods
      such as environmental benefits suggests that public investment may supplant
      private motivation. Using aerial photography we mapped the extent of
      revegetation, native vegetation fencing and restoration on 71 representative
      landholdings in rural south-eastern Australia. We interviewed each landholder and
      recorded the age and funding model of each site. Contrary to the local "x2"
      reporting assumption, about 75% of the total area of the 412 sites was from
      subsidised sites, and that proportion was far higher for the period after 1997.
      However, rather than displacing unsubsidised activity, our modelling showed that
      landholders who had recently been subsidised for a project were more likely to
      have subsequently completed unsubsidised work. This indicates that, at least in
      terms of medium-term economic impact, the large increase in public subsidies did
      not diminish privately funded activity, as might be expected according to the
      theory of crowding out. 

PMID- 24576672
TI  - Interaction of mutant p53 with p73: a Surface Plasmon Resonance and Atomic Force
      Spectroscopy study.
AB  - BACKGROUND: TP53 tumor suppressor gene is mutated in more than 50% of human
      tumors. Mutated p53 proteins could sequestrate and inactivate p73 reducing the
      apoptotic and anti-proliferative effects of the transcription factor, and
      yielding cancer cells more aggressive and chemoresistant. The possibility of
      using drugs to prevent the mutant p53/p73 complex formation preserving the p73
      function, calls for a deeper insight into the molecular and biochemical
      mechanisms of mutant p53/p73 protein interaction. METHODS: The kinetics of the
      mutant p53R175H/p73 complex was investigated with innovative and complementary
      techniques, operating in real time, in near physiological conditions and without
      any labeling. Specifically, Atomic Force Spectroscopy and Surface Plasmon
      Resonance working at single-molecule level and in bulk condition, respectively,
      were used. RESULTS: The two techniques revealed that a stable complex is formed
      between mutant p53R175H and p73 proteins; the complex being characterized by a
      high interaction force and a dissociation equilibrium constant in the order of
      10(-7)M, as expected for specific interactions. No binding was instead observed
      between p73 and wild type p53. CONCLUSIONS: Mutant p53R175H protein, unlike wild
      type p53, can form a stable complex with p73. The mutant p53R175H/p73 protein
      complex could be a target for innovative pharmaceutical drugs that, by
      dissociating it or preventing biomolecule interaction thus preserving the p73
      function, could enhance the response of cancerous cells carrying mutant p53R175H
      protein to common chemotherapeutic agents. GENERAL SIGNIFICANCE: The kinetic
      information obtained in vitro may help to design specific pharmaceutical drugs
      directed against cancerous cells carrying mutant p53 proteins.

PMID- 24576673
TI  - Non-collagenous ECM proteins in blood vessel morphogenesis and cancer.
AB  - BACKGROUND: The extracellular matrix (ECM) is constituted by diverse composite
      structures, which determine the specific to each organ, histological architecture
      and provides cells with biological information, mechanical support and a scaffold
      for adhesion and migration. The pleiotropic effects of the ECM stem from the
      dynamic changes in its molecular composition and the ability to remodel in order
      to effectively regulate biological outcomes. Besides collagens, fibronectin and
      laminin are two major fiber-forming constituents of various ECM structures. SCOPE
      OF REVIEW: This review will focus on the properties and the biological functions
      of non-collagenous extracellular matrix especially on laminin and fibronectin
      that are currently emerging as important regulators of blood vessel formation and
      function in health and disease. MAJOR CONCLUSIONS: The ECM is a fundamental
      component of the microenvironment of blood vessels, with activities extending
      beyond providing a vascular scaffold; extremely versatile it directly or
      indirectly modulates all essential cellular functions crucial for angiogenesis,
      including cell adhesion, migration, proliferation, differentiation and lumen
      formation. Specifically, fibronectin and laminins play decisive roles in blood
      vessel morphogenesis both during embryonic development and in pathological
      conditions, such as cancer. GENERAL SIGNIFICANCE: Emerging evidence demonstrates
      the importance of ECM function during embryonic development, organ formation and
      tissue homeostasis. A wealth of data also illustrates the crucial role of the ECM
      in several human pathophysiological processes, including fibrosis, skeletal
      diseases, vascular pathologies and cancer. Notably, several ECM components have
      been identified as potential therapeutic targets for various diseases, including
      cancer. This article is part of a Special Issue entitled Matrix-mediated cell
      behaviour and properties.

PMID- 24576674
TI  - G-quadruplex DNA recognition by nucleophosmin: new insights from protein
      dissection.
AB  - BACKGROUND: Nucleophosmin (NPM1, B23) is a multifunctional protein that is
      involved in a variety of fundamental biological processes. NPM1/B23 deregulation
      is implicated in the pathogenesis of several human malignancies. This protein
      exerts its functions through the interaction with a multiplicity of biological
      partners. Very recently it is has been shown that NPM1/B23 specifically
      recognizes DNA G-quadruplexes through its C-terminal region. METHODS: Through a
      rational dissection approach of protein here we show that the intrinsically
      unfolded regions of NPM1/B23 significantly contribute to the binding of c-MYC G
      quadruplex motif. Interestingly, the analysis of the ability of distinct NPM1/B23
      fragments to bind this quadruplex led to the identifications of distinct NPM1/B23
      based peptides that individually present a high affinity for this motif. RESULTS:
      These results suggest that the tight binding of NPM1/B23 to the G-quadruplex is
      achieved through the cooperation of both folded and unfolded regions that are
      individually able to bind it. The dissection of NPM1/B23 also unveils that its H1
      helix is intrinsically endowed with an unusual thermal stability. CONCLUSIONS:
      These findings have implications for the unfolding mechanism of NPM1/B23, for the
      G-quadruplex affinity of the different NPM1/B23 isoforms and for the design of
      peptide-based molecules able to interact with this DNA motif. GENERAL
      OBSERVATION: This study sheds new light in the molecular mechanism of the complex
      NPM1/G-quadruplex involved in acute myeloid leukemia (AML) disease.

PMID- 24576671
TI  - The first cyclomegastigmane rhododendroside A from Rhododendron brachycarpum
      alleviates HMGB1-induced sepsis.
AB  - BACKGROUND: Endangered plant species are a vital resource for exploring novel
      drug prototypes. A Korean endangered plant Rhododendron brachycarpum G. Don is a
      broad-leaved shrub native to northern Korea and central Japan. The high mobility
      group box 1 protein (HMGB1) could be a specific target for the discovery of novel
      antiseptic agents. METHODS: Gauge-invariant atomic orbital (GIAO) NMR chemical
      shift calculations were applied for investigation of stereochemical details with
      accuracy improved by application of DP4 analysis. In vitro antiseptic mechanisms
      were investigated utilizing immunofluorescence staining, ELISA and cell-cell
      adhesion assay. Cecal ligation and puncture (CLP) operation was employed to
      evaluate in vivo potential alleviating severe sepsis and septic shock. RESULTS:
      The first bicyclic megastigmane glucoside rhododendroside A (1) along with known
      megastigmane glucosides (2-5) were isolated from the leaves of R. brachycarpum.
      The structure of 1 was established by NMR analysis as well as comparison of the
      experimental chemical shifts with those of computed values employing DP4
      application. In the CLP operation model that simulates severe sepsis,
      rhododendroside A (1) improved the survival rate up to 60%. CONCLUSIONS: Our
      results exhibit that R. brachycarpum may produce a unique scaffold that is
      developed into a drug lead mitigating HMGB1-induced vascular pro-inflammatory
      stimuli and thus alleviating severe sepsis and related manifestations. GENERAL
      SIGNIFICANCE: Discovery of new drug leads would warrant conservation efforts of
      endangered species.

PMID- 24576675
TI  - LRRK2, but not pathogenic mutants, protects against H2O2 stress depending on
      mitochondrial function and endocytosis in a yeast model.
AB  - BACKGROUND: Mutations in LRRK2 are the most common genetic cause of Parkinson's
      disease (PD). Studies in the yeast Saccharomyces cerevisiae have provided
      valuable insights into the mechanisms of cellular dysfunction associated with the
      expression of faulty PD genes. METHODS: We developed a yeast model for full
      length LRRK2 studies. We expressed wild-type (wt) LRRK2 and mutations and
      evaluated their role during oxidative stress conditions. The involvement of
      mitochondria was assessed by using rho-zero mutants and by evaluating reactive
      oxygen species (ROS) production and mitochondrial membrane potential by flow
      cytometry. The involvement of endocytosis was also studied by testing several
      endocytic mutants and by following the vacuolar delivery of the probe FM4-64.
      RESULTS: Expression of LRRK2 in yeast was associated to increased hydrogen
      peroxide resistance. This phenotype, which was dependent on mitochondrial
      function, was not observed for PD-mutants G2019S and R1441C or in the absence of
      the kinase activity and the WD40 repeat domain. Expression of the pathogenic
      mutants stimulated ROS production and increased mitochondrial membrane potential.
      For the PD-mutants, but not for wild-type LRRK2, endocytic defects were also
      observed. Additionally, several endocytic proteins were required for LRRK2
      mediated protection against hydrogen peroxide. CONCLUSIONS: Our results indicate
      that LRRK2 confers cellular protection during oxidative stress depending on
      mitochondrial function and endocytosis. GENERAL SIGNIFICANCE: Both the loss of
      capacity of LRRK2 pathogenic mutants to protect against oxidative stress and
      their enhancement of dysfunction may be important for the development of PD
      during the aging process.

PMID- 24576676
TI  - [Psychological alterations in patients with adult celiac disease].
AB  - Patients with recently-diagnosed adult celiac disease were evaluated with the
      Gastrointestinal Symptom rating Scale (GSRS) and Psychological General Well-Being
      Index (PGWBI) to evaluate their psychological alterations, the association
      between any alterations and gastrointestinal symptoms, and their outcome after
      starting a gluten-free diet. The patients underwent nutritional assessment and
      then started a gluten-free diet; they were reassessed 6 months later.
      Quantitative variables are expressed as the median and 25th-75th percentiles.
      RESULTS: We included 21 patients, 17 women and 4 mena, with a mean age of 43
      years (31-47). The results of histological analysis were compatible with Marsh I
      lesions in 6 patients, Marsh IIIa in 6 and Marsh IIIb in 9. At baseline, 8
      patients showed severe psychological distress, 4 showed moderate distress and 9
      showed no distress. The GSRS score was 34 (17-43) and the PGWBI was 64 (48-87),
      with a significant correlation between the 2 indexes (rho=-.58, P=.006). At 6
      months, 3 patients had severe psychological distress, 5 had moderate distress, 9
      showed no distress and 4 showed psychological well-being. The GSRS score at 6
      months was 13 (8-17) and the PGWBI was 83 (68-95) (P<.05 compared with baseline
      data for the 3 indicators). The 6 axes of the PGWBI showed significant
      improvement. At 6 months, no correlation was found between the GSRS and PGWBI.
      CONCLUSIONS: Patients with celiac disease have psychological alterations whose
      intensity is related to gastrointestinal symptoms. These symptoms improve after
      the start of a gluten-free diet.

PMID- 24576677
TI  - [Telaprevir-induced cutaneous lesions].

PMID- 24576678
TI  - Diet dependent experience and physiological state shape the behavior of a
      generalist herbivore.
AB  - The performance of herbivorous insects depends on a balance of nutrient uptake
      and toxin avoidance. Whereas high concentrations of defensive plant metabolites
      impair both generalists and specialists, generalists are likely less adapted to
      particular hosts and thus more negatively affected by plant defense traits.
      Furthermore, resulting diet-dependent differences in the physiological state and
      the gained experience of an animal may shape its behavior. Here, we investigated
      the effects of life-long experience with leaves of different quality on the
      performance and various behavioral traits of the generalist leaf beetle Galeruca
      tanaceti. Rearing individuals continuously on three different diets [young
      leaves, old leaves, or leaves of different age of cabbage (Brassicaceae) in
      alternating order every other day], we found that relative growth rates (RGRs) of
      the larvae were higher when feeding on young leaves than when feeding on the
      other diets. Feeding on leaves of different age in alternating order reduced the
      performance of G. tanaceti, indicating costs involved in diet mixing. The
      experience gained by the respective food qualities shaped the preference behavior
      in adult beetles. Positive and negative feedbacks of animals reared on young or
      old leaves, respectively, led to a preference towards young leaves. In contrast,
      feedback was probably prevented for animals reared on alternating diet, which did
      not exhibit any preferences. Older adults did not show any diet-dependent
      differences in body mass due to physiological changes during adult development. A
      battery of behavioral tests with the older adults revealed that the behavior was
      consistent over context and partially over time but behaviors did not differ in
      dependence of the diet experience. We retrieved three personality dimensions for
      this species, namely boldness, activity, and exploration. The behavioral
      structure was very similar to earlier findings for another chrysomelid species,
      indicating a broader validity of the concept of personality dimensions in
      insects. Our results demonstrate the importance of both experience- and state
      dependence when investigating behavioral phenotypes. 

PMID- 24576681
TI  - Coupling between inter-helical hydrogen bonding and water dynamics in a proton
      transporter.
AB  - Long-distance proton transfers by proton pumps occurs in discrete steps that may
      involve the direct participation of protein sidechains and water molecules, and
      coupling of protonation changes to structural rearrangements of the protein
      matrix. Here we explore the role of inter-helical hydrogen bonding in long
      distance protein conformational coupling and dynamics of internal water
      molecules. From molecular dynamics simulations of wild type and nine different
      bacteriorhodopsin mutants we find that both intra- and inter-helical hydrogen
      bonds are important determinants of the local protein structure, dynamics, and
      water interactions. Based on molecular dynamics and bioinformatics analyses, we
      identify an aspartate/threonine inter-helical hydrogen-bonding motif involved in
      controlling the local conformational dynamics. Perturbation of inter-helical
      hydrogen bonds can couple to rapid changes in water dynamics. 

PMID- 24576680
TI  - Neonatal infection modulates behavioral flexibility and hippocampal activation on
      a Morris Water Maze task.
AB  - Neonatal infection has enduring effects on the brain, both at the cellular and
      behavioral levels. We determined the effects of peripheral infection with
      Escherichia coli at postnatal day (P) 4 in rats on a water maze task in
      adulthood, and assessed neuronal activation in the dentate gyrus (DG) following
      the memory test. Rats were trained and tested on one of 3 distinct water maze
      task paradigms: 1) minimal training (18 trials/3days), 2) extended training (50
      trials/10days) or 3) reversal training (extended training followed by 30
      trials/3days with a new platform location). Following a 48h memory test, brains
      were harvested to assess neuronal activation using activity-regulated
      cytoskeleton-associated (Arc) protein in the DG. Following minimal training, rats
      treated neonatally with E. coli had improved performance and paradoxically
      reduced Arc expression during the memory test compared to control rats treated
      with PBS early in life. However, neonatally-infected rats did not differ from
      control rats in behavior or neuronal activation during the memory test following
      extended training. Furthermore, rats treated neonatally with E. coli were
      significantly impaired during the 48h memory test for a reversal platform
      location, unlike controls. Specifically, whereas neonatally-infected rats were
      able to acquire the new location at the same rate as controls, they spent
      significantly less time in the target quadrant for the reversal platform during a
      memory test. However, neonatally-infected and control rats had similar levels of
      Arc expression following the 48h memory test for reversal. Together, these data
      indicate that neonatal infection may improve the rate of acquisition on
      hippocampal-dependent tasks while impairing flexibility on the same tasks; in
      addition, network activation in the DG during learning may be predictive of
      future cognitive flexibility on a hippocampal-dependent task. 

PMID- 24576682
TI  - Decoration of silk fibroin by click chemistry for biomedical application.
AB  - Silkfibroin (SF) has an excellent biocompatibility and its remarkable structure
      translates into exciting mechanical properties rendering this biomaterial
      particularly fascinating for biomedical application. To further boost the
      material's biological/preclinical impact, SF is decorated with biologics,
      typically by carbodiimide/N-hydroxysuccinimide coupling (EDC/NHS). For biomedical
      application, this chemistry challenges the product risk profile due to the
      formation of covalent aggregates, particularly when decoration is with biologics
      occurring naturally in humans as these aggregates may prime for autoimmunity.
      Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC; click chemistry) provides the
      necessary specificity to avoid such intermolecular, covalent aggregates. We
      present a blueprint outlining the necessary chemistry rendering SF compatible
      with CuAAC and with a particular focus on structural consequences. For that, the
      number of SF carboxyl groups (carboxyl-SF; required for EDC/NHS chemistry) or
      azido groups (azido-SF; required for click chemistry) was tailored by means of
      diazonium coupling of the SF tyrosine residues. Structural impact on SF and
      decorated SF was characterized by Fourier transform infrared spectroscopy (FTIR).
      The click chemistry yielded a better controlled product as compared to the
      EDC/NHS chemistry with no formation of inter- and intramolecular crosslinks as
      demonstrated for SF decorated with fluorescent model compounds or a biologic,
      fibroblast growth factor 2 (FGF2), respectively. In conclusion, SF can readily be
      translated into a scaffold compatible with click chemistry yielding decorated
      products with a better risk profile for biomedical application. 

PMID- 24576683
TI  - Retinoic acid induced repair in the lung of adult hyperoxic mice, reducing
      transforming growth factor-beta1 (TGF-beta1) mediated abnormal alterations.
AB  - The aim of the study was to determine the effects of retinoic acid on lung
      alveolar repair in adult hyperoxic mice and to investigate the relationship
      between TGF-beta1 and retinoic acid during the repair processes. Adult mice were
      divided into 4 groups. Two groups were given daily intraperitoneal injections of
      peanut oil/dimethylsulfoxide mixture and retinoic acid (50mg/kg body weight, 50
      MUl of volume) dissolved in peanut oil/dimethylsulfoxide mixture for 12 days with
      a 2-day break on days 6 and 7. Following hyperoxia (100% oxygen) for 72 h the
      remaining two groups were treated in the same manner as already described: peanut
      oil/dimethylsulfoxide mixture and retinoic acid. Lung structure was investigated
      by light microscopy. TGF-beta1 and Smad protein expressions in the lung were
      assayed by biochemical methods. Hyperoxic mice exhibited damage to the alveolar
      walls, increased cell proliferation and induced Smad3/TGF-beta1 signaling. Smad2
      and phospho-Smad2 protein expressions were unchanged in all groups. Retinoic acid
      administration improved the degenerative alterations caused by hyperoxia and
      helped in alveolar repair. This positive effect of retinoic acid resulted from
      the inhibition of Smad3/TGF-beta1 signaling via reduced Smad4 mRNA and increased
      Smad7 protein expression. Retinoic acid also induced alveolarization and
      restricted Smad3/TGF-beta1 signaling by decreasing Smad4 mRNA in healthy mice.
      Thus, retinoic acid helped repair Smad3/TGF-beta1-induced lung damage in
      hyperoxic mice.

PMID- 24576684
TI  - Tomatoes cause under-arm odour.
AB  - Under arm odour [axillary odour AO, bromidrosis] is a deeply unpleasant problem
      that can affect a person's self confidence and esteem and reduce social
      interaction. It is generally managed by good hygiene along with antiperspirants
      and deodorants, but the axillary apocrine glands may need surgical removal in
      severe cases of odour. The odour comes from microbial conversion of the apocrine
      secretions into short chain fatty acids like isovaleric acid and volatile sulphur
      compounds like 3-sulphanylhexan-1-ol. These can be detected at a few parts per
      billion to parts per trillion by the human nose so an unhygienic state is soon
      apparent. Recently genetics have been found to play an important role too as
      people with the AA variant of the ATP-binding cassette (ABC) transporter gene,
      ABCC11, do not secrete preodour substrates for bacterial conversion, while those
      with GA or GG variants do. Hygiene and genetics, are an incomplete explanation
      though, because the longitudinal ALSPAC study found that there is a mismatch
      between patients' secretory status, as determined by genetics, and their use of
      deodorants. This suggests that other metabolic pathways or compounds contribute
      to the odour. In this paper I propose that under arm odour is commonly caused by
      terpenes excreted via the axillary apocrine glands. I also show that these come
      from terpene and carotenoid-rich dietary sources including lycopene, tomatoes,
      orange peel and the glandular trichomes of tomato plants. These observations
      suggest that the axillary apocrine glands are a prominent excretory route for
      terpenes. Considering the quantities eaten, tomatoes are likely to be the main
      source of dietary terpenes, and under arm odour in turn. This study also shows
      that lycopene is probably metabolised by beta-carotene 9 10 monooxygenase which
      cleaves beta-carotene eccentrically at the 9 10 or 9'10' position of the chain.
      Direct evidence of lycopene metabolism by beta-carotene 9 10 monooxygenase has
      hitherto been lacking. The study of terpene and carotenoid metabolism can be
      greatly advanced by analysing the content of axillary gland excretions. 

PMID- 24576679
TI  - Peripheral interleukin-2 level is associated with negative symptoms and cognitive
      performance in schizophrenia.
AB  - Although several studies have pointed to a possible role of interleukin 2 (IL-2)
      in schizophrenia (SZ), association between IL-2 and the different groups of
      symptoms has not been explored. The objective of this study was to investigate a
      possible correlation of peripheral IL-2 levels with symptoms and cognitive
      performance in patients with SZ. In addition, we compared the plasma levels of IL
      2 between patients with SZ and healthy controls. Twenty-nine chronically
      medicated outpatients with SZ according to DSM-IV were compared with twenty-six
      healthy controls. The patients were evaluated with the Positive and Negative
      Syndrome Scale (PANSS), the Calgary Depression Scale for Schizophrenia (CDSS),
      the Clinical Global Impression (CGI) and the Global Assessment of Functioning
      (GAF). All the participants had blood collected into EDTA tubes by venipuncture
      between 9:00 and 10:00AM. Plasma concentrations of IL-2 were determined by
      cytometric bead array. A computerized neuropsychological battery assessed verbal
      learning, verbal fluency, working memory, set shifting, executive function,
      inhibition and intelligence. Patients with SZ had lower levels of IL-2 than
      healthy controls (p<0.001). In the SZ group, IL-2 levels were positively
      correlated with scores in the digit span test (rho=0.416, P=0.025) and
      intelligence (rho=0.464, P=0.011). We also found a negative correlation between
      IL-2 and total score in the negative subscale of PANSS (rho=-0.447, p=0.015). Our
      findings suggest that IL-2 may be involved in the mechanisms related to cognitive
      deterioration and negative symptomatology in schizophrenia. 

PMID- 24576685
TI  - Coffee consumption and risk of fractures: a systematic review and dose-response
      meta-analysis.
AB  - PURPOSE: The data on the association between coffee consumption and the risk of
      fractures are inconclusive. We performed a comprehensive literature review and
      meta-analysis to better quantify this association. METHODS: We identified all
      potentially relevant articles by searching MEDLINE, EMBASE, Cochrane Library, Web
      of Science, SCOPUS, and CINAHL (until February 2013). The keywords "coffee,"
      "caffeine," "drink," and "beverage" were used as the exposure factors, and the
      keyword "fracture" was used as the outcome factor. We determined the overall
      relative risk (RR) and confidence interval (CI) for the highest and lowest levels
      of coffee consumption. A dose-response analysis was performed to assess the risk
      of fractures based on the level of coffee consumption. RESULTS: We included
      253,514 participants with 12,939 fracture cases from 9 cohort and 6 case-control
      studies. The estimated RR of fractures at the highest level of coffee consumption
      was 1.14 (95% CI: 1.05-1.24; I(2)=0.0%) in women and 0.76 (95% CI: 0.62-0.94;
      I(2)=7.3%) in men. In the dose-response analysis, the pooled RRs of fractures in
      women who consumed 2 and 8 cups of coffee per day were 1.02 (95% CI: 1.01-1.04)
      and 1.54 (95% CI: 1.19-1.99), respectively. CONCLUSIONS: Our meta-analysis
      suggests that daily consumption of coffee is associated with an increased risk of
      fractures in women and a contrasting decreased risk in men. However, future well
      designed studies should be performed to confirm these findings.

PMID- 24576686
TI  - Testosterone rapidly increases neural reactivity to threat in healthy men: a
      novel two-step pharmacological challenge paradigm.
AB  - BACKGROUND: Previous research suggests that testosterone (T) plays a key role in
      shaping competitive and aggressive behavior in humans, possibly by modulating
      threat-related neural circuitry. However, this research has been limited by the
      use of T augmentation that fails to account for baseline differences and has been
      conducted exclusively in women. Thus, the extent to which normal physiologic
      concentrations of T affect threat-related brain function in men remains unknown.
      METHODS: In the current study, we use a novel two-step pharmacologic challenge
      protocol to overcome these limitations and to evaluate causal modulation of
      threat- and aggression-related neural circuits by T in healthy young men (n =
      16). First, we controlled for baseline differences in T through administration of
      a gonadotropin releasing hormone antagonist. Once a common baseline was
      established across participants, we then administered T to within the normal
      physiologic range. During this second step of the protocol we acquired functional
      neuroimaging data to examine the impact of T augmentation on neural circuitry
      supporting threat and aggression. RESULTS: Gonadotropin releasing hormone
      antagonism successfully reduced circulating concentrations of T and brought
      subjects to a common baseline. Administration of T rapidly increased circulating
      T concentrations and was associated with heightened reactivity of the amygdala,
      hypothalamus, and periaqueductal grey to angry facial expressions. CONCLUSIONS:
      These findings provide novel causal evidence that T rapidly potentiates the
      response of neural circuits mediating threat processing and aggressive behavior
      in men.

PMID- 24576688
TI  - Follow-up and extension of a prior genome-wide association study of posttraumatic
      stress disorder: gene * environment associations and structural magnetic
      resonance imaging in a highly traumatized African-American civilian population.

PMID- 24576689
TI  - Baicalein ameliorated the upregulation of striatal glutamatergic transmission in
      the mice model of Parkinson's disease.
AB  - Parkinson's disease (PD) is a common neurodegenerative disorder, which is
      characterized by a loss of projecting dopaminergic neurons in the substantia
      nigra and diminished dopamine level in the striatum. Dopaminergic deficit
      consequently leads to the alterations of striatal basal glutamatergic synaptic
      transmission and plasticity in the medium spiny neurons. The cytokines and
      neurotoxins released from the reactive immune cells induced the loss of the
      projecting dopaminergic neurons in the substantia nigra, which triggering the
      pathogenesis of PD. The present study investigated the effect of treatment with
      baicalein (5,6,7-trihydroxyflavone) on the central cytokine synthesis, striatal
      glutamatergic transmission, and behavioral performance in the rotarod task in the
      mice injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Treatment
      with baicalein significantly attenuated the upregulation of striatal basal
      glutamatergic strength by decreasing the presynaptic glutamate release and
      recovering the insertion of postsynaptic glutamate receptor subunit GluR1 induced
      by MPTP. It also significantly improved the behavioral performance in the rotarod
      task in the mice injected with MPTP. Treatment with baicalein decreased the
      upregulation of cytokines (tumor necrosis factor-alpha and interleukin-1beta) in
      the substantia nigra and striatum in the mice injected with MPTP. These results
      indicated that baicalein might serve as novel approach for the treatment of the
      patients with PD.

PMID- 24576690
TI  - The deeper sources of political conflict: evidence from the psychological,
      cognitive, and neuro-sciences.
AB  - Political disputes ruin family reunions, scuttle policy initiatives, and spur
      violence and even terrorism. We summarize recent research indicating that the
      source of political differences can be found in biologically instantiated and
      often subthreshold predispositions as reflected in physiological, cognitive, and
      neural patterns that incline some people toward innovation and others toward
      conservatism. These findings suggest the need to revise traditional views that
      maintain that political opinions are the product of rational, conscious,
      socialized thought. 

PMID- 24576691
TI  - Diabetes in older people: Prevalence, incidence and its association with medium-
      and long-term mortality from all causes.
AB  - OBJECTIVE: To estimate the prevalence and incidence of self-reported diabetes and
      to study its association with medium- and long-term mortality from all causes in
      persons >= 65 years. DESIGN: A population-based cohort study begun in 1993.
      SETTING: "Envejecer en Leganes" cohort (Madrid). PARTICIPANTS: A random sample of
      persons >= 65 years (n=1277 in the 1993 baseline sample). METHODS: Participants
      were classified as having diabetes if they so reported and had consulted a
      physician for this reason within the last year. Diabetes history was categorized
      in <10 and >= 10 years in 1993. Incidence density was calculated in 2-year
      periods in non-diabetic individuals (1965 persons/2 years). Vital status was
      recorded on 31 December 2011. The association between diabetes history >= 10
      years and mortality at 6 and 18 years follow-up was studied by the Kaplan-Meier
      and Cox regression analyses after adjusting for age, sex, heart disease and
      comorbidity. RESULTS: The prevalence of self-reported diabetes rose from 10.3% in
      1993 to 16.1% in 1999 (p <= 0.001) and was higher in women than men (p <= 0.05).
      Total incidence density was 2.6 cases/100 persons/2 years (95% CI: 2.0-3.3).
      Medium- and long-term mortality was higher in persons with diabetes history >= 10
      years than in non-diabetic individuals (HR: 2.0; 95% CI: 1.2-3.3 and HR: 1.7; 95%
      CI: 1.1-2.5, respectively). In diabetics with history <10 years the HR was 1.3
      (95% CI: 0.9-1.9) and HR: 1.5 (95% CI: 1.2-1.9, respectively). CONCLUSIONS:
      Although diabetes is clearly associated with increased risk of mortality, it is
      significant only for patients with >= 10 years' history of diabetes.

PMID- 24576687
TI  - Enduring deficits in brain reward function after chronic social defeat in rats:
      susceptibility, resilience, and antidepressant response.
AB  - BACKGROUND: Anhedonia, or diminished interest or pleasure in rewarding
      activities, characterizes depression and reflects deficits in brain reward
      circuitries. Social stress induces anhedonia and increases risk of depression,
      although the effect of social stress on brain reward function is incompletely
      understood. METHODS: This study assessed the following: 1) brain reward function
      in rats (using the intracranial self-stimulation procedure) and protein levels of
      brain-derived neurotrophic factor and related signaling molecules in response to
      chronic social defeat, 2) brain reward function during social defeat and long
      term treatment with the antidepressants fluoxetine (5 mg/kg/day) and desipramine
      (10 mg/kg/day), and 3) forced swim test behavior after social defeat and
      fluoxetine treatment. RESULTS: Social defeat profoundly and persistently
      decreased brain reward function, reflecting an enduring anhedonic response, in
      susceptible rats, whereas resilient rats showed no long-term brain reward
      deficits. In the ventral tegmental area, social defeat, regardless of
      susceptibility or resilience, decreased brain-derived neurotrophic factor and
      increased phosphorylated AKT, whereas only susceptibility was associated with
      increased phosphorylated mammalian target of rapamycin. Fluoxetine and
      desipramine reversed lower, but not higher, stress-induced brain reward deficits
      in susceptible rats. Fluoxetine decreased immobility in the forced swim test, as
      did social defeat. CONCLUSIONS: These results suggest that the differential
      persistent anhedonic response to psychosocial stress may be mediated by ventral
      tegmental area signaling molecules independent of brain-derived neurotrophic
      factor and indicate that greater stress-induced anhedonia is associated with
      resistance to antidepressant treatment. Consideration of these behavioral and
      neurobiological factors associated with resistance to stress and antidepressant
      action may promote the discovery of novel targets to treat stress-related mood
      disorders.

PMID- 24576693
TI  - Common white matter microstructure alterations in pediatric motor and attention
      disorders.
AB  - OBJECTIVE: To characterize white matter alterations in children with isolated or
      concurrent developmental coordination disorder and/or attention
      deficit/hyperactivity disorder (ADHD) compared with typically-developing
      controls, and to determine whether group differences on motor and attention tasks
      could be explained by differences in diffusion tensor imaging (DTI) measures.
      STUDY DESIGN: In a cohort of children (n = 85) with developmental coordination
      disorder, ADHD, or combined developmental coordination disorder+ADHD, we examined
      3 major white matter tracts involved in attention and motor processes. Using DTI,
      the corpus callosum, superior longitudinal fasciculus, and cingulum were analyzed
      with respect to measures of white matter integrity. Differences in fractional
      anisotropy (FA), mean diffusivity, radial diffusivity, and axial diffusivity were
      analyzed using ANOVA. Motor and attentional functioning was assessed using
      standardized tests, and correlated to DTI measures. RESULTS: FA reductions were
      noted in the frontal regions of the corpus callosum for children with ADHD (P =
      .039), whereas children with developmental coordination disorder displayed
      similar reductions in regions of the corpus callosum underlying parietal brain
      regions (P = .040), as well as the left superior longitudinal fasciculus (P =
      .026). White matter integrity was impacted in both frontal and parietal regions
      for children with comorbid developmental coordination disorder+ADHD (P = .029;
      .046). FA was positively correlated with scores on both motor and attentional
      assessments in a region-specific manner. CONCLUSION: Our findings suggest that
      alterations in the corpus callosum underlie difficulties in motor and attention
      functioning. These changes are functionally and regionally distinct and could
      reflect a neurobiological basis for motor and attention disorders in children.

PMID- 24576694
TI  - Use of a gum elastic bougie in a penetrating neck trauma.
AB  - The case of a patient with a zone II penetrating neck injury who was intubated
      successfully utilizing the gum elastic bougie (GEB) is reported. He presented at
      a forward operational base in Afghanistan with a shrapnel wound in his neck as
      well as a cough and hoarseness. There were two wounds on each side of his
      laryngeal cartilages. The patient's breathing rate gradually increased and
      labored inhalation developed while the aeromedical evacuation was delayed for
      tactical reasons. Subcutaneous emphysema and edema concealed the anatomical
      landmarks, making a cricothyrotomy unsafe, and no fiber optic devices were
      available on site. Intratracheal intubation was decided upon by the doctors
      involved. Because of the anticipated difficultly of intubation, the GEB was used
      from the outset. During direct laryngoscopy, edema, blood, and mucus concealed
      the anatomic reliefs of the larynx. The glottis was not visible. On the second
      attempt, "clicks" were clearly perceived and the tube was railroaded over the
      bougie. Finally, the patient was evacuated to an Afghan military hospital. In
      this report, the benefit-risk balance for the use of the GEB in penetrating neck
      trauma is discussed. Although the use of the GEB cannot be recommended in all
      cases of penetrating neck injury, it should be considered as an option. This
      technique is not without risk, but in very remote settings or hostile
      environments, especially when cricothyrotomy is not possible, it can be
      lifesaving.

PMID- 24576695
TI  - Heavy metal recovery combined with H2 production from artificial acid mine
      drainage using the microbial electrolysis cell.
AB  - The aim of this study was to utilize the microbial electrolysis cell (MEC) for
      metal removal from acid mine drainage (AMD) and simultaneous H2 production. A
      dual-chamber MEC was developed to concurrently produce H2 and remove Cu(2+),
      Ni(2+), and Fe(2+) from AMD under single and mixed metal conditions. With an
      applied voltage of 1.0V, Cu(2+) in the AMD was prior to others to be recovered at
      the cathode, followed by Ni(2+), and finally Fe(2+). The H2 production rates
      achieved during the AMD treatment were in the range of 0.4-1.1m(3)m(-3)d(-1), and
      the highest rate was obtained with the AMD containing single Cu(2+). The highest
      efficiency of cathode electron recovery reached 89%, which was obtained with the
      AMD containing mixed metals. The recovered electrons were used for both H2
      production and metal reduction. The energy recovery efficiency of MEC reached up
      to 100%, suggesting that H2 generated from AMD was sufficient to offset the
      energy input during the treatment. The MEC was successfully applied to remove
      metals from the AMD, recover value-added products of Cu(0) and Ni(0), and to
      produce H2. 

PMID- 24576696
TI  - Changes in hemodynamic signals accompanying motor imagery and motor execution of
      swallowing: a near-infrared spectroscopy study.
AB  - In the present study we investigated hemodynamic changes in the brain in response
      to motor execution (ME) and motor imagery (MI) of swallowing using near-infrared
      spectroscopy (NIRS). Previous studies provide evidence that ME and MI of limb
      movements lead to comparable brain activation patterns indicating the potential
      value of MI for motor rehabilitation. In this context, identifying brain
      correlates of MI of swallowing may be potentially useful for the treatment of
      dysphagia. Fourteen healthy participants actively swallowed water (ME) and
      mentally imagined to swallow water (MI) in a randomized order while changes in
      concentration of oxygenated hemoglobin (oxy-Hb) and deoxygenated hemoglobin
      (deoxy-Hb) were assessed. MI and ME led to the strongest NIRS signal changes in
      the inferior frontal gyrus. During and after ME, oxy-Hb significantly increased,
      with a maximum peak around 15s after task onset. In contrast, oxy-Hb decreased
      during MI compared to a rest period probably because of motor inhibition
      mechanisms. Changes in deoxy-Hb were largely comparable between MI and ME,
      especially when participants used a kinesthetic motor imagery strategy during MI
      compared to no specific strategy. Hence, the present study provides new evidence
      concerning timing and topographical distribution of the hemodynamic response
      during ME and MI of swallowing.

PMID- 24576697
TI  - Biomass retention on electrodes rather than electrical current enhances stability
      in anaerobic digestion.
AB  - Anaerobic digestion (AD) is a well-established technology for energy recovery
      from organic waste streams. Several studies noted that inserting a
      bioelectrochemical system (BES) inside an anaerobic digester can increase biogas
      output, however the mechanism behind this was not explored and primary controls
      were not executed. Here, we evaluated whether a BES could stabilize AD of
      molasses. Lab-scale digesters were operated in the presence or absence of
      electrodes, in open (no applied potential) and closed circuit conditions. In the
      control reactors without electrodes methane production decreased to 50% of the
      initial rate, while it remained stable in the reactors with electrodes,
      indicating a stabilizing effect. After 91 days of operation, the now colonized
      electrodes were introduced in the failing AD reactors to evaluate their
      remediating capacity. This resulted in an immediate increase in CH4 production
      and VFA removal. Although a current was generated in the BES operated in closed
      circuit, no direct effect of applied potential nor current was observed. A high
      abundance of Methanosaeta was detected on the electrodes, however irrespective of
      the applied cell potential. This study demonstrated that, in addition to other
      studies reporting only an increase in methane production, a BES can also
      remediate AD systems that exhibited process failure. However, the lack of
      difference between current driven and open circuit systems indicates that the key
      impact is through biomass retention, rather than electrochemical interaction with
      the electrodes. 

PMID- 24576698
TI  - Caged mudsnail Potamopyrgus antipodarum (Gray) as an integrated field
      biomonitoring tool: exposure assessment and reprotoxic effects of water column
      contamination.
AB  - This study highlights the usefulness of gastropods for water quality monitoring.
      Gastropods were caged upstream and downstream of an effluent discharge. Exposure
      was assessed by measurement of organic contaminants in water. Contamination of
      the Potamopyrgus antipodarum mudsnail was also measured using innovative
      techniques at the end of the 42 days of exposure. Biological effects were
      measured at the individual level (growth, reproduction) and subindividual level
      (energy reserves, vitellin-like proteins, steroid levels, expression of genes
      involved in estrogen signaling pathways), thus providing a better understanding
      of reprotoxic effects. The effluent was mainly contaminated by pharmaceutical
      compounds, as was the mudsnail. The highest concentrations were measured for
      oxazepam and were higher than 2 mg/kg downstream of the effluent discharge.
      Alkylphenols, bisphenol A, and vertebrate-like sex-steroid hormones were also
      bioaccumulated by the mudsnail downstream of the effluent. The combined use of
      water and snail contamination provided a complete exposure assessment. Exposure
      was further linked to biological effects. The mudsnail was shown to be a better
      adapted species for in situ exposures than Valvata piscinalis. Reproduction was
      sharply decreased after 6 weeks of exposure in the mudsnail. Feeding issues were
      excluded, confirming the toxic origin. These effects were related to estrogen
      signaling pathways using genomic analysis. Genes coding for proteins involved in
      nongenomic signaling pathways were inhibited, and those of genomic pathway
      repressors were induced. These results suggest that the chemical contamination
      due to the effluent discharge altered steroid control of reproduction and blocked
      the transition between oocyte and unshelled embryo, resulting in a drastic
      decrease of embryo production, while survival was not affected. 

PMID- 24576699
TI  - Effect of water chemistry on the dissolution rate of the lead corrosion product
      hydrocerussite.
AB  - Hydrocerussite (Pb3(CO3)2(OH)2) is widely observed as a corrosion product in
      drinking water distribution systems. Its equilibrium solubility and dissolution
      rate can control lead concentrations in drinking water. The dissolution rate of
      hydrocerussite was investigated as a function of pH, dissolved inorganic carbon
      (DIC), and orthophosphate concentrations at conditions relevant to drinking water
      distribution using continuously stirred tank reactors (CSTRs). In the absence of
      DIC and orthophosphate, the dissolution rate decreased with increasing pH.
      Addition of DIC inhibited the dissolution of hydrocerussite. The addition of
      orthophosphate significantly decreased the dissolution rate of hydrocerussite. At
      conditions with orthophosphate and without DIC, a lead(II) phosphate solid
      hydroxylpyromorphite (Pb5(PO4)3OH) was observed after reaction, and
      orthophosphate's inhibitory effect can be attributed to the formation of this low
      solubility lead(II) phosphate solid. In the presence of both orthophosphate and
      DIC, no lead(II) phosphate solid was observed, but the rate was still lowered by
      the presence of orthophosphate, which might be due to the adsorption of
      orthophosphate to block reactive sites on the hydrocerussite surface. For systems
      in which hydroxylpyromorphite was present, the steady-state effluent lead
      concentrations from the CSTRs were close to the predicted equilibrium solubility
      of hydroxylpyromorphite. In the absence of orthophosphate rapid equilibration of
      hydrocerussite was observed. 

PMID- 24576700
TI  - Effects of D-amino acids and norspermidine on the disassembly of large, old-aged
      microbial aggregates.
AB  - The increasing threat of microbial aggregates in many fields highlights the need
      to develop methods to promote their disassembly. This study investigated the
      coupled effects of d-tyrosine (d-Tyr) and norspermidine on the disassembly of a
      type of old-aged (more than 6 months), large (about 900 MUm) microbial aggregate
      formed by mixed culture. Results showed that d-Tyr and norspermidine acting
      together effectively triggered the disassembly of microbial aggregates, with
      disassembly ratio enhanced by 30-164% compared to the control at the
      concentration of 50-500 MUM of d-Tyr and norspermidine. d-Tyr and norspermidine
      reduced the content of extracellular protein and polysaccharide in microbial
      aggregates and altered the matrix structure of extracellular polymeric substances
      as confirmed by a confocal laser scanning microscope. The microbial aggregates
      lost stability after treatment with d-Tyr and norspermidine as could be seen from
      the increase in surface negative charge and decrease in cell hydrophobicity.
      Fourier transform infrared spectroscopy analysis revealed that norspermidine
      could directly interact with polysaccharide and caused the disappearance of an IR
      band at 1152 cm(-1) that may be correlated with the functional group C-O-C.
      Overall, the combined application of d-amino acids and norspermidine offers an
      effective approach to disassemble large and resistant microbial aggregates. 

PMID- 24576701
TI  - Health risk assessment for splash parks that use rainwater as source water.
AB  - In the Netherlands, rainwater becomes more and more popular as an economic and
      environmentally sustainable water source for splash parks, however, the
      associated public health risk and underlying risk factors are unknown. Since
      splash parks have been associated with outbreaks of infectious diseases, a
      quantitative microbial risk assessment was performed using Legionella pneumophila
      as a target pathogen to quantify the risk of infection for exposure due to
      inhalation and Campylobacter jejuni for ingestion. Data for L. pneumophila and C.
      jejuni concentrations in rainfall generated surface runoff from streets were
      extracted from literature. Data for exposure were obtained by observing 604
      people at splash parks, of whom 259 were children. Exposure volumes were
      estimated using data from literature to determine the volume of exposure through
      inhalation at 0.394 MUL/min (95% CI-range 0.0446-1.27 MUL/min), hand-to-mouth
      contact at 22.6 MUL/min, (95% CI-range 2.02-81.0 MUL/min), ingestion of water
      droplets at 94.4 MUL/min (95% CI-range 5.1-279 MUL/min) and ingestion of
      mouthfuls of water at 21.5.10(3) MUL/min (95% CI-range 1.17 .10(3)-67.0.10(3)
      MUL/min). The corresponding risk of infection for the mean exposure duration of
      3.5 min was 9.3.10(-5) (95% CI-range 0-2.4.10(-4)) for inhalation of L.
      pneumophila and 3.6.10(-2) (95% CI-range 0-5.3.10(-1)) for ingestion of C.
      jejuni. This study provided a methodology to quantify exposure volumes using
      observations on site. We estimated that using rainwater as source water for
      splash parks may pose a health risk, however, further detailed quantitative
      microbial analysis is required to confirm this finding. Furthermore we give
      insight into the effect of water quality standards, which may limit infection
      risks from exposure at splash parks. 

PMID- 24576703
TI  - Regulating emotions uniquely modifies reaction time, rate of force production,
      and accuracy of a goal-directed motor action.
AB  - We investigated how emotion regulation (ER) strategies influence the execution of
      a memory guided, ballistic pinch grip. Participants (N=33) employed ER strategies
      (expressive suppression, emotional expression, and attentional deployment) while
      viewing emotional stimuli (IAPS images). Upon stimulus offset, participants
      produced a targeted pinch force aimed at 10% of their maximum voluntary
      contraction. Performance measures included reaction time (RT), rate of force
      production, and performance accuracy. As hypothesized, attentional deployment
      resulted in the slowest RT, largest rate of force production, and poorest
      performance accuracy. In contrast, expressive suppression reduced the rate of
      force production and increased performance accuracy relative to emotional
      expression and attentional deployment. Findings provide evidence that emotion
      regulation strategies uniquely influence human movement. Future work should
      further delineate the interacting role that emotion regulation strategies have in
      modulating both affective experience and motor performance. 

PMID- 24576702
TI  - A fundamental role for context in instrumental learning and extinction.
AB  - The purpose of this article is to review recent research that has investigated
      the effects of context change on instrumental (operant) learning. The first part
      of the article discusses instrumental extinction, in which the strength of a
      reinforced instrumental behavior declines when reinforcers are withdrawn. The
      results suggest that extinction of either simple or discriminated operant
      behavior is relatively specific to the context in which it is learned: As in
      prior studies of Pavlovian extinction, ABA, ABC, and AAB renewal effects can all
      be observed. Further analysis supports the idea that the organism learns to
      refrain from making a specific response in a specific context, or in more formal
      terms, an inhibitory context-response association. The second part of the article
      then discusses research suggesting that the context also controls instrumental
      behavior before it is extinguished. Several experiments demonstrate that a
      context switch after either simple or discriminated operant training causes a
      decrement in the strength of the response. Over a range of conditions, the animal
      appears to learn a direct association between the context and the response. Under
      some conditions, it can also learn a hierarchical representation of context and
      the response-reinforcer relation. Extinction is still more context-specific than
      conditioning, as indicated by ABC and AAB renewal. Overall, the results establish
      that the context can play a significant role in both the acquisition and
      extinction of operant behavior. 

PMID- 24576704
TI  - Coordination tendencies are shaped by attacker and defender interactions with the
      goal and the ball in futsal.
AB  - This study examined how the location of the goal and ball constrained the
      interpersonal coordination tendencies emerging of attacker-defender dyadic
      systems in team sports. Additionally, we analysed how the positioning of
      defenders constrained the emergent coordination tendencies between the ball
      carrier and supporting teammates. To investigate these tendencies in team sports,
      ten futsal games were filmed to observe inter-individual interactions. Movement
      trajectories of players and ball were digitized during 52 outfield attacker
      defender interactions involving thirteen goal-scoring sequences. Relative phase
      was used as a measure to express participant coordination tendencies in these
      dyadic systems (in-phase or symmetry - 0 degrees ; anti-phase or anti-symmetry -
      180 degrees ). Stable in-phase patterns of coordination emerged between specific
      values of an attacker's distances to defenders and the goal (19% frequency from 0
      degrees  to 29 degrees  of phase relations) and between specific values of
      distances of ball carriers to defenders and teammates (14% frequency from 0
      degrees  to 29 degrees  of phase relations). A stable pattern of coordination of 
      60 degrees  emerged between values of an attacker's distances to defenders and
      the ball (18% frequency from 0 degrees  to 29 degrees  of phase relations).
      Distances of attackers to the goal and ball, and distances of ball carriers to
      defenders, seemed to be coupled in a specific manner to guide interpersonal
      coordination tendencies between players during competitive performance in the
      team sport of futsal. 

PMID- 24576705
TI  - Time-motion analysis of acceleration demands of 4v4 small-sided soccer games
      played on different pitch sizes.
AB  - We aimed to quantify the time-motion characteristics and technical demands of
      small-sided soccer games (SSGs) played on small, medium and large pitches using a
      high frequency non-differential global positioning system (NdGPS) that allowed
      assessment of acceleration and deceleration patterns. Eight male soccer players
      competed in SSGs comprising 4*4min quarters (3min recovery) on small (30*20m)
      medium (40*30m) and large (50*40m) pitch sizes. Time motion analysis using a
      NdGPS positioning system quantified distance covered sprinting (?6.7ms(-1)), high
      speed running (?5.8ms(-1)) and low (1-2ms(-2)), medium (2-3ms(-2)) and high
      (>3ms(-2)) acceleration. The frequency of common technical actions (passing,
      turning, dribbling, shooting, tackling, heading and interceptions) was performed
      using a hand notation system. SSGs played on medium and large pitches had a
      greater physical demand than on small pitches, with significantly more distance
      covered in all movement categories. Total distance covered in acceleration
      categories ranged from 230+/-111 (small pitch) to 356+/-72m (medium pitch). The
      small pitch imposed a greater technical demand on players (more passes, shots and
      tackles) compared to medium and large pitches. The study provides novel data
      demonstrating the acceleration patterns observed in SSGs are relatively greater
      than those observed during professional match play. Thus SSGs might offer a
      "density" type conditioning stimulus. Practitioners should be aware that changes
      in pitch size impact both the physical and technical demands of SSGs. 

PMID- 24576706
TI  - The effect of instruction to synchronize over step frequency while walking with
      auditory cues on a treadmill.
AB  - Walking to a pacing stimulus has proven useful in motor rehabilitation, and it
      has been suggested that spontaneous synchronization could be preferable to
      intentional synchronization. But it is still unclear if the paced walking effect
      can occur spontaneously, or if intentionality plays a role. The aim of this work
      is to analyze the effect of sound pacing on gait with and without instruction to
      synchronize, and with different rhythmic auditory cues, while walking on a
      treadmill. Firstly, the baseline step frequency while walking on a treadmill was
      determined for all participants, followed by experimental sessions with both
      music and footstep sound cues. Participants were split into two groups, with one
      being instructed to synchronize their gait to the auditory stimuli, and the other
      being simply told to walk. Individual auditory cues were generated for each
      participant: for each trial, cues were provided at the participant's baseline
      walking frequency, at 5% and 10% above baseline, and at 5% and 10% below
      baseline. This study's major finding was the role of intention on
      synchronization, given that only the instructed group synchronized their gait
      with the auditory cues. No differences were found between the effects of step or
      music stimuli on step frequency. In conclusion, without intention or cues that
      direct the individual's attention, spontaneous gait synchronization does not
      occur during treadmill walking. 

PMID- 24576708
TI  - Influences of a diet supplemented with linseed oil and antioxidants on quality of
      equine semen after cooling and cryopreservation during winter.
AB  - Seasonal changes in the reproductive physiology of stallions contribute to a
      decrease in the quality of frozen-thawed semen during late winter. Changes in the
      lipid composition of the sperm plasma membrane may contribute to this phenomenon.
      In the present study, we have, therefore, investigated the effects of adding
      linseed oil (LO) in combination with antioxidants to the diet of breeding
      stallions on the motility and membrane integrity of cooled-stored and
      cryopreserved semen. Starting in November, the diet of LO stallions (n = 6) but
      not control (C) stallions (n = 5) was supplemented with LO (100 mL once daily)
      plus an antioxidant (Myostem Protect; Audevard, Clichy, France) for a total of 84
      days. Before (November) and at the end of this period (February), ejaculates were
      processed for cryopreservation (n = 3 ejaculates per stallion) and cooled
      shipping at 5  degrees C. Frozen-thawed and cooled-shipped semen was sent to the
      laboratory for computer-assisted semen analysis of total motility, progressive
      motility, and velocity parameters (average path velocity [VAP], curved line
      velocity [VCL], and straight-line velocity [VSL]) and evaluation of membrane
      integrity. The quality of frozen-thawed semen decreased (P < 0.05) from November
      (e.g., total motility LO 69 +/- 3% and C 67 +/- 3%) to February (total motility:
      LO 55 +/- 4% and C 59 +/- 3%) independent of treatment (P > 0.05). A decrease in
      the velocity parameters VAP, VCL, and VSL was more pronounced in LO stallions
      than in C stallions (e.g., VSL: November LO 67 +/- 1 MUm/s, C 64 +/- 2 MUm/s;
      February LO 59 +/- 2 MUm/s, C 63 +/- 2 MUm/s; interaction month by treatment, P <
      0.05). In cooled-stored semen, total motility, progressive motility, and membrane
      integrity were lower in February than in November (P < 0.001 for all parameters).
      Supplementation of the diet with LO and antioxidants attenuated this decrease
      (e.g., Day 1 of cooled storage = 24 hours after semen collection: total motility
      in November LO 88 +/- 1% and C 87 +/- 3%; in February LO 83 +/- 2% and C 73 +/-
      11%; interaction month by treatment: P < 0.05). Velocity parameters VAP, VCL, and
      VSL were significantly lower in February than in November (P < 0.001), but this
      decrease was not affected by treatment. In summary, dietary supplementation of
      stallions with LO plus antioxidants attenuated a decline in motility and membrane
      integrity of cooled-stored stallion semen during winter. This may improve the
      fertility of cooled-shipped semen. In contrast, the treatment did not counteract
      the decrease in quality of frozen-thawed semen that occurs in late winter. 

PMID- 24576707
TI  - Effect of aerobic training on inter-arm coordination in highly trained swimmers.
AB  - The effect of three months of aerobic training on spatio-temporal and
      coordination parameters was examined during a swim trial at maximal aerobic
      speed. Nine male swimmers swam a 400-m front crawl at maximal speed twice: in
      trial 1, after summer break, and trial 2, after three months of aerobic training.
      Video analysis determined the stroke (swimming speed, stroke length, and stroke
      rate) and coordination (Index of Coordination and propulsive phase duration)
      parameters for every 50-m segment. All swimmers significantly increased their
      swimming speed after training. For all swimmers except one, stroke length
      increased and stroke rate remained constant, whereas the Index of Coordination
      and the propulsive phase duration decreased (p<.05). This study suggests that
      aerobic training developed a greater force impulse in the swimmers during the
      propulsive phases, which allowed them to take advantage of longer non-propulsive
      phases. In this case, catch-up coordination, if associated with greater stroke
      length, can be an efficient coordination mode that reflects optimal
      drag/propulsion adaptation. This finding thus provides new insight into swimmers'
      adaptations to the middle-distance event. 

PMID- 24576709
TI  - The orphan nuclear receptor SF-1 is involved in the effect of PCBs, DDT, and DDE
      on the secretion of steroid hormones and oxytocin from bovine luteal cells during
      the estrous cycle in vitro.
AB  - The orphan receptor steroidogenic factor-1 (SF-1) is involved in the regulation
      of ovarian steroidogenesis in cows. It is hypothesized that estrogen-like
      chlorinated compounds might affect SF-1, and thus impair the function of the
      ovary. Bovine luteal cells from the estrous cycle (Days: 1-5, 6-10, 11-15, and 16
      19) were treated for 50 hours with DDT, 1,1-dichloro-2,2-bis(4
      chlorophenyl)ethene, 3,3'4,4'-tetrachlorobiphenyl or 2'2'4,4',5,5'
      hexachlorobiphenyl (each at a dose of 10 ng/mL). Luteal cells were also treated
      with 4-(heptyloxy)phenol (1 * 10(-7) M), an SF-1 agonist, and F0160 (1 * 10(-6)
      M), an SF-1 blocker, jointly or separately. The secretion of progesterone and
      oxytocin and the expression of oxytocin precursor (NP-I/OT) messenger RNA were
      increased (P < 0.05) by all studied xenobiotics and 4-(heptyloxy)phenol, although
      they were inhibited (P < 0.05) by F0160. However, the xenobiotics did not affect
      (P > 0.05) SF-1 messenger RNA expression. In summary, SF-1 is involved in the
      adverse effect of chlorinated xenobiotics on the regulation of the bovine CL. 

PMID- 24576710
TI  - Developmental competence of IVM pig oocytes after SCNT in relation to the
      shrinkage pattern induced by hyperosmotic treatment.
AB  - The objective of this study was to examine the developmental competence of IVM
      pig oocytes in relation to the pattern of morphologic changes after exposure to
      hyperosmotic medium to select oocytes of a higher quality. IVM oocytes were
      treated with a hyperosmotic (593 mOsm) medium containing NaCl, sorbitol, or
      sucrose. Oocytes that shrunk spherically (SSP oocytes) or in irregular shapes
      (SIR oocytes) were collected separately, and washed for 15 minutes in an isotonic
      (297 mOsm) medium for recovery. Irrespective of the chemicals used, hyperosmotic
      treatment of oocytes for 1 hour or 15 minutes did not alter embryonic development
      after parthenogenesis (PA) and SCNT. A significantly higher proportion of SSP
      oocytes developed to the blastocyst stage (34.0%) compared with SIR oocytes
      (15.8%) after PA. The intracellular glutathione content was significantly higher
      in SSP oocytes than in SIR oocytes. Conversely, the reactive oxygen species level
      was significantly higher in SIR oocytes than in SSP oocytes. The maturation
      promoting factor level as measured by p34(cdc2) kinase activity was not
      influenced by hyperosmotic treatment itself but was 1.3-fold higher (P < 0.05) in
      SSP oocytes than in SIR oocytes. When IVM oocytes were divided into two groups
      according to their diameters (large and small), and treated separately in
      hyperosmotic medium, significantly more SSP oocytes (71.4%) were found in the
      large oocytes than in the small oocytes (51.4%). Moreover, the proportion of
      metaphase II oocytes was significantly higher in SSP oocytes than in SIR oocytes
      in both groups (98.5% vs. 73.1% in large oocytes, and 92.2% vs. 48.0% in small
      oocytes). After SCNT, a significantly higher proportion of SSP oocytes displayed
      blastocyst formation (36.4%) than untreated (29.0%) and SIR oocytes (22.1%). Our
      results demonstrated that SSP oocytes were of a higher quality than SIR oocytes,
      which was shown by higher intracellular glutathione and maturation promoting
      factor levels, lower reactive oxygen species levels, and improved embryonic
      development to the blastocyst stage after PA and SCNT. 

PMID- 24576711
TI  - Advancing maternal age predisposes to mitochondrial damage and loss during
      maturation of equine oocytes in vitro.
AB  - In many mammalian species, reproductive success decreases with maternal age. One
      proposed contributor to this age-related decrease in fertility is a reduction in
      the quantity or functionality of mitochondria in oocytes. This study examined
      whether maternal age or (in vitro maturation). IVM affect the quantity of
      mitochondria in equine oocytes. Oocytes were collected from the ovaries of
      slaughtered mares categorized as young (<12 years) or aged (>=12 years) and
      either denuded and prepared for analysis immediately (not-IVM) or matured in
      vitro for 30 hours before preparation (IVM). The mean oocyte mitochondrial DNA
      copy number was estimated by quantitative polymerase chain reaction and found to
      be significantly lower in oocytes from aged mares and that had been subjected to
      IVM than in any other group. Transmission electron microscopy demonstrated that
      mitochondria in aged mare oocytes subjected to IVM experienced significantly more
      swelling and loss of cristae than in other groups. We conclude that maternal
      aging is associated with a heightened susceptibility to mitochondrial damage and
      loss in equine oocytes, which manifests during IVM. This predisposition to
      mitochondrial degeneration probably contributes to reduced fertility in aged
      mares. 

PMID- 24576712
TI  - Effects of frozen and liquid hypothermic storage and extender type on calcium
      homeostasis in relation to viability and ATP content in striped bass (Morone
      saxatilis) sperm.
AB  - The effect of hypothermic storage on striped bass sperm calcium homeostasis was
      determined by Fluo-3 flow cytometry. Calcium homeostasis was defined as the
      ability of cells to maintain a low concentration of intracellular free calcium as
      measured by Fluo-3 fluorescence. Sperm were stored frozen in striped bass
      extender (SBE) and Tris-NaCl medium (T350) modified with 50 mM glycine and 7.5%
      dimethylsulfoxide and in nonfrozen form diluted 1:3 (vol/vol) in SBE and T350 for
      1, 24, and 48 hours at 4  degrees C in an oxygen atmosphere. Fluo-3 fluorescence
      was detected in less than 5% of fresh viable sperm cells indicating maintenance
      of calcium homeostasis. In contrast to sperm in fresh semen, frozen-thawed and
      nonfrozen sperm cells lost to a considerable extent the ability to maintain low
      intracellular free calcium even in the absence of exogenous calcium; positive
      Fluo-3 fluorescence was found in 26% and 39% of thawed sperm frozen in SBE- and
      T350-based freezing diluents, respectively, and increased (P < 0.05) to 67%
      during nonfrozen storage in SBE and T350 at 24 and 48 hours. Sperm viability
      measured by exclusion of propidium iodide by flow cytometry was 99% in fresh milt
      and maintained at 86% (P > 0.05) in SBE after 48 hours of nonfrozen storage but
      decreased (P < 0.05) to 55.7% after 48 hours in T350. Energy status in terms of
      ATP content, determined by luciferin-luciferase bioluminescence assay, was higher
      (P < 0.05) in sperm frozen in SBE than in T350 during the first 5 minutes post
      thaw and decreased to essentially zero by 15 minutes post-thaw and did not differ
      among nonfrozen storage treatments. In conclusion, sperm cells impervious to
      propidium iodide after frozen or nonfrozen storage were unable to maintain low
      intracellular calcium content. SBE is a better medium than T350 for frozen or
      nonfrozen storage of striped bass sperm. The inability to regulate intracellular
      calcium in striped bass sperm may be associated with poor activation of motility
      after 4  degrees C storage and cryopreservation.

PMID- 24576713
TI  - Clinical evaluation of different applications of misoprostol and aglepristone for
      induction of abortion in bitches.
AB  - The aim of the present study was to compare the clinical and endocrinological
      effects of different applications of misoprostol (MIS) and aglepristone (AGL) for
      the induction of abortion in bitches. For this purpose, 28 healthy pregnant
      bitches from different breeds, ages, body weights (Body weigt, BWs, 10-40 kg),
      and between Days 25 to 35 of gestation were used. Bitches were randomly assigned
      to four groups. In group 1 (GI, n = 7), AGL (10 mg/kg BW, s.c. on 2 consecutive
      days); in group 2 (GII, n = 7), AGL (as in GI), intravaginal MIS (IVag, 200 MUg
      for bitches with <=20 kg BW, 400 MUg for bitches with >20 kg BW, daily
      intravaginally until completion of abortion); in group 3 (GIII, n = 7), AGL (as
      in GI), ICVag (as in GII), per os MIS (400 MUg for bitches with <=20 kg BW, 800
      MUg for bitches with >20 kg BW, daily orally, until completion of abortion); in
      group 4 (GIV, n = 7), AGL (as in GI), per os MIS (as GIII) were used. Clinical,
      vaginal, and ultrasonographic examinations were performed daily until abortion
      was completed. For measurement of serum progesterone, blood samples were
      collected in all groups immediately after the first AGL administration and every
      other day until completion of abortion. No statistical differences were found
      between groups concerning the duration until completion of abortion after
      treatment (nonsignificant); however, in GII, one bitch completed abortion 2 days
      after the start of treatment. 

PMID- 24576714
TI  - Effects of fumonisin B1 alone and combined with deoxynivalenol or zearalenone on
      porcine granulosa cell proliferation and steroid production.
AB  - Fumonisin B1 (FB1) is a Fusarium mycotoxin frequently occurring in corn in
      combination with deoxynivalenol (DON) and zearalenone. The aim of this study was
      to determine if FB1, alone and combined with DON or alpha-zearalenol (ZEA),
      zearalenone major active metabolite, can affect granulosa cell proliferation,
      steroid production, and gene expression in swine. Porcine granulosa cells were
      cultured for 2 days in serum-containing medium followed by 1 or 2 days in serum
      free medium with or without added treatments. Fumonisin B1 had inhibitory effects
      on granulosa cell proliferation. Deoxynivalenol strongly inhibited cell growth,
      and no significant difference was detected in combination with FB1. alpha
      Zearalenol showed a stimulatory effect on granulosa cell numbers even in
      combination with FB1. Regarding steroid production, FB1 increased progesterone
      production, and FB1 had no effect on estradiol production. Deoxynivalenol
      strongly inhibited progesterone and estradiol production, and FB1 had no
      significant effect on this response. alpha-Zearalenol increased progesterone
      production, and its combination with FB1 produced additive effects. alpha
      Zearalenol had no effect on estradiol production, whereas it decreased estradiol
      production when co-treated with FB1. Fumonisin B1 was found to decrease CYP11A1
      messenger RNA abundance, and the stimulatory effect of FB1 on progesterone
      production was found to be not dependent on 3-hydroxy-3-methylglutaryl-coenzyme A
      reductase activity suggesting that FB1 increases progesterone production through
      a different mechanism. The results show that these Fusarium mycotoxins can
      influence porcine granulosa cell proliferation and steroid production, thereby
      demonstrating their potential reproductive effects on swine.

PMID- 24576715
TI  - Mucin 1 and cytokines mRNA in endometrium of dairy cows with postpartum uterine
      disease or repeat breeding.
AB  - Mucin (MUC) 1 is an inducible innate immune effector, an important component of
      defense against bacterial invasion, and is linked with infertility in humans. The
      objectives were to evaluate messenger RNA (mRNA) expression of MUC1 and cytokine
      genes in the endometrium of cows with various postpartum uterine inflammatory
      conditions or with a history of repeat breeding. Endometrial samples were
      collected from lactating dairy cows diagnosed with metritis (n = 4), endometritis
      (n = 4), subclinical endometritis (n = 4), or no uterine pathology (normal; n =
      4). In addition, endometrial samples were collected from repeat breeder cows with
      (n = 4) or without (n = 4) subclinical endometritis, and unaffected cows (n = 4).
      Quantitative polymerase chain reaction was used to determine mRNA abundances of
      MUC1, Toll-like receptor (TLR) 4, interleukin (IL) 1beta, IL6, IL8, tumor
      necrosis factor (TNF) alpha, insulin-like growth factor (IGF) 1, and IGF-binding
      protein (BP) 2. The mRNA expressions were significantly greater for cows with
      metritis and clinical endometritis compared with cows with no uterine
      inflammation, except for IL6. However, mRNA expressions for these target genes
      were not different for cows with subclinical endometritis, compared with cows
      without uterine inflammation, except for IL1beta and TNFalpha mRNA (P < 0.01).
      All mRNA expressions were greater (P < 0.001) for repeat breeder cows with
      subclinical endometritis compared with normal cows. However, in repeat breeder
      cows without subclinical endometritis, only expressions of MUC1, IGF1, and IGF
      BP2 were greater compared with normal cows (P < 0.01). Based on functional
      protein networks, there were significant associations between these transcripts.
      In conclusion, endometrial expressions of MUC1 and cytokine genes differed among
      normal, fertile versus diseased, and subfertile dairy cows. Perhaps, these
      altered gene expressions contribute to endometrial insufficiency and consequently
      pregnancy wastage. 

PMID- 24576716
TI  - Effect of temporary meiosis block during prematuration of bovine cumulus-oocyte
      complexes on pregnancy rates in a commercial setting for in vitro embryo
      production.
AB  - Ovum pick up (OPU) associated with in vitro production (IVP) of embryos has been
      shown as an important tool in cattle breeding to increase the number of
      descendants from animals of high genetic value. In herds maintained distant from
      the laboratory, collecting cumulus-oocyte complexes (COCs) and transporting them
      to the laboratory may take several hours and decrease COCs viability,
      representing a challenge for commercial settings. In this study, a prematuration
      culture to induce temporary meiosis block was evaluated in a commercial scale IVP
      setting as a strategy to transport bovine OPU-derived COCs from Nelore and
      Brangus donors. Effects on embryo yield and pregnancy rates were assessed. Viable
      COCs from each donor were destined to one of the experimental groups (control,
      blocks 1 and 2). Control group COCs were placed in cryotubes with 1 mL TCM199
      HEPES. In block groups (1 and 2), COCs were placed in cryotubes with 300 MUL TCM
      199 + 12 MUM butyrolactone I (block medium). All groups were gassed and kept in a
      thermos bottle for 4 hours at 36  degrees C. Next, COCs in the control group were
      transferred to IVM medium and block 1 group to block medium, and cultured for 22
      hours and 15 hours, respectively, at 38.5  degrees C and 5% CO2 in air. Block 2
      COCs were kept in the cryotubes and in the thermos bottle for another 15 hours at
      36  degrees C to simulate long-term transport conditions. After meiosis block in
      prematuration culture, blocks 1 and 2 COCs were matured in vitro for 22 hours as
      for the control group. After IVM, COCs in all groups were submitted to IVF and
      IVC, and blastocyst rates were evaluated on day 7. Embryos were transferred and
      pregnancy rates evaluated at 60 days of gestation. The mean total number of COCs
      retrieved by OPU did not differ between Nelore and Brangus donors (16.8 and 17.2,
      respectively, P > 0.05), but Nelore donors produced more viable COCs than Brangus
      (10.1 and 7.6, respectively, P < 0.05) and more embryos/cow (3.8 and 2.7,
      respectively, P < 0.05). Blastocyst rates were similar for control (40.2% and
      36.7%), block 1 (37.3% and 34.5%), and block 2 groups (34.7% and 33.6%) for
      Nelore and Brangus cattle, respectively (P > 0.05). Pregnancy rates did not
      differ regardless of breed or treatment (36.7%, P > 0.05). In conclusion,
      temporary meiosis block during prematuration culture did not affect embryo
      development or pregnancy rates; therefore, this strategy may be used to transport
      bovine COCs in a commercial IVP setting. 

PMID- 24576718
TI  - Pulmonary rhabdomyomatous dysplasia of the newborn in neurofibromatosis type 1.
AB  - Proliferation of non-neoplastic striated muscle cells in the lung is rare and has
      been frequently observed in cases of cardiovascular and pulmonary congenital
      malformations. We present an extremely rare case of pulmonary rhabdomyomatous
      dysplasia (RD) in neurofibromatosis type 1 (NF-1). A male neonate was born at 35
      weeks' gestation after normal pregnancy. Postnatally, besides patent ductus
      arteriosus and posterior mediastinal mass, abnormal cystic lesions in the left
      upper and lower lung were detected. No bronchial atresia and stenosis were
      identified. Partial lobectomy specimens showed hypoplastic lung parenchyma with
      cystic lesions resembling terminal bronchioles and distinctive proliferation of
      non-neoplastic striated muscle fibers in the interstitium. The posterior
      mediastinal mass consisted of neurofibroma. Considering that cafe au lait spots
      and freckling occurred at 2 months of age, a diagnosis of NF-1 was made. The
      patient died of aspiration pneumonia at the age of 30 months. To the best of our
      knowledge, this is the first case of pulmonary RD in NF-1. 

PMID- 24576717
TI  - Professional training in nutrition in Central and Eastern Europe: current status
      and opportunities for capacity development.
AB  - OBJECTIVE: To examine the availability of academic programmes in nutrition and
      identify nutrition training needs in Central and Eastern Europe (CEE). DESIGN: A
      questionnaire with close-ended and open-ended questions was distributed to the
      members of the United Nations University Standing Committee on Nutrition,
      Regional Network for Capacity Development in Nutrition in CEE (NCDN CEE).
      SETTING: Participants' responses to the questionnaire including the comments of
      their colleagues from home institutions were obtained in group discussions during
      NCDN CEE meetings in 2010-2013. SUBJECTS: Sixteen CEE countries' experts and
      their colleagues from home institutions involved in NCDN CEE activities 2007
      2013. RESULTS: The responses were obtained from fourteen out of sixteen
      participating countries; five countries have established Bachelor, Master and PhD
      studies in nutrition (Croatia, Czech Republic, Poland, Slovak Republic and
      Slovenia), whereas in Latvia and Republic of Macedonia only Bachelor and Master
      studies are set up. Seven countries have no Bachelor, Master or PhD studies:
      Bosnia and Herzegovina, Bulgaria, Estonia, Lithuania, Montenegro, Romania and
      Serbia. Introduction to data analysis and Nutritional epidemiology are the most
      needed nutrition trainings that would increase working competence of
      nutritionists and nutrition-related professionals in CEE. CONCLUSIONS:
      Availability of academic programmes in nutrition in CEE countries is limited.
      Opportunities for improving the competence of existing and future nutrition
      related professionals should be addressed at national and regional level;
      distance learning courses and creation of a regional centre for nutrition
      training were seen as opportunities for sustainable capacity development in
      nutrition in CEE.

PMID- 24576719
TI  - The study of anatomic structures in establishing the posterior seal area for
      maxillary complete dentures.
AB  - STATEMENT OF PROBLEM: The spatial relationship between the foveae palatinae and
      vibrating lines varies among individuals; such variability could be related to
      the contour of the palate. PURPOSE: The purpose of this study was to investigate
      the relative location of the foveae palatinae and vibrating lines and to
      determine the correlation between the seal area of the posterior palate and the
      palatal contour with lateral cephalogram radiography. MATERIAL AND METHODS: Fifty
      participants were examined. The Valsalva maneuver was used to determine the
      anterior vibrating line, and the phonation ('ah') method was used to detect the
      posterior vibrating line. The distance from the anterior to the posterior
      vibrating line and the distances between the foveae palatinae and the anterior
      and posterior vibrating lines were measured. A lateral cephalogram was made to
      trace the hard and soft palate contour, and the angle of the palatal contour was
      measured with the V-ceph program. Correlation analysis was conducted with
      statistical software to examine the relation between the distance from the
      anterior to the posterior vibrating line and the angle of the palatal contour at
      the junction of the hard and soft palate. RESULTS: The anterior vibrating line
      was located approximately 2.58 +/-1.19 mm anterior to the foveae palatinae, and
      the posterior vibrating line was located 0.71 +/-0.68 mm posterior. A positive
      correlation was found between the distance from the anterior to the posterior
      vibrating line in the lateral sagittal plane and the angle of the palatal contour
      at the junction of the hard and soft palate. Correlation coefficients were 0.495
      in the left sagittal plane and 0.560 in the right sagittal plane (P<.05).
      CONCLUSIONS: Considering their proximity to the posterior vibrating line, the
      foveae palatinae could be reliable reference points for locating the posterior
      border of the maxillary denture. The results of this study also suggest that a
      wider posterior palatal seal area could be obtained if the patient has a gentle
      palatal contour at the junction of the hard and soft palate.

PMID- 24576720
TI  - Transcutaneous electric acupoint stimulation reduces intra-operative remifentanil
      consumption and alleviates postoperative side-effects in patients undergoing
      sinusotomy: a prospective, randomized, placebo-controlled trial.
AB  - BACKGROUND: Although opioids are widely used as analgesics in general
      anaesthesia, they have unpleasant side-effects and can delay postoperative
      recovery. Acupuncture and related techniques are effective for acute and chronic
      pain, and reduces some side-effects. We assessed the effect of transcutaneous
      electric acupoint stimulation (TEAS) on intra-operative remifentanil consumption
      and the incidences of anaesthesia-related side-effects. METHODS: Sixty patients
      undergoing sinusotomy were randomly assigned to TEAS or control group. TEAS
      consisted of 30 min of stimulation (6-9 mA, 2/10 Hz) on the Hegu (LI4), Neiguan
      (PC6), and Zusanli (ST36) before anaesthesia. The patients in the control group
      had the electrodes applied, but received no stimulation. Bispectral index was
      used to monitor the depth of anaesthesia. Perioperative haemodynamics were
      recorded, and peripheral blood samples were collected to measure the levels of
      mediators of surgical stress. The primary end point was intraoperative
      remifentanil consumption and the secondary endpoints were recovery quality and
      anaesthesia-related side-effects. RESULTS: Patients in the TEAS group required
      39% less remifentanil during surgery than controls [0.0907 (SD 0.026) MUg kg(-1)
      min(-1) vs 0.051 (0.018) MUg kg(-1) min(-1)]. There were no differences in intra
      operative haemodynamics or surgical stress between groups. However, the time to
      extubation and recall in the control group was 16.8 (6.8) min and 23.0 (5.0) min,
      respectively, significantly longer than that in the TEAS group (P<0.01). TEAS
      also decreased the incidence of dizziness and pruritus within the first 24 h
      after surgery (P<0.01). CONCLUSION: The use of TEAS significantly reduced intra
      operative remifentanil consumption and alleviated postoperative side-effects in
      patients undergoing sinusotomy. CLINICAL TRIAL REGISTRATION: The trial was
      registered at clinicaltrials.gov (NCT01700855).

PMID- 24576721
TI  - Safety belt and mobile phone usage in vehicles in Barcelona (Spain).
AB  - OBJECTIVES: To describe the prevalence and correlates of safety belt and mobile
      phone usage in vehicles in the city of Barcelona (Spain). METHODS: We performed a
      study using direct observation with a cross-sectional design. We selected 2,442
      private cars, commercial vehicles, and taxis from all districts of Barcelona.
      RESULTS: The prevalence of people not wearing safety belt was 10.5% among
      drivers, 4.6% among front seat passengers, and 32.2% among some of the rear
      passengers. It was higher among the passengers than among the drivers, regardless
      of the type of the vehicle. The prevalence of mobile phone usage while driving
      during a moment of the trip was 3.8%. CONCLUSION: Our study shows noticeably high
      prevalence of people not wearing safety belt in the rear seats. Moreover, four
      out of one hundred drivers still use the mobile phone while driving during a
      moment of the trip.

PMID- 24576722
TI  - TCDD induces dermal accumulation of keratinocyte-derived matrix metalloproteinase
      10 in an organotypic model of human skin.
AB  - The epidermis of skin is the first line of defense against the environment. A
      three dimensional model of human skin was used to investigate tissue-specific
      phenotypes induced by the environmental contaminant, 2,3,7,8-tetrachlorodibenzo-p
      dioxin (TCDD). Continuous treatment of organotypic cultures of human
      keratinocytes with TCDD resulted in intracellular spaces between keratinocytes of
      the basal and immediately suprabasal layers as well as thinning of the basement
      membrane, in addition to the previously reported hyperkeratinization. These
      tissue remodeling events were preceded temporally by changes in expression of the
      extracellular matrix degrading enzyme, matrix metalloproteinase-10 (MMP-10). In
      organotypic cultures MMP-10 mRNA and protein were highly induced following TCDD
      treatment. Q-PCR and immunoblot results from TCDD-treated monolayer cultures, as
      well as indirect immunofluorescence and immunoblot analysis of TCDD-treated
      organotypic cultures, showed that MMP-10 was specifically contributed by the
      epidermal keratinocytes but not the dermal fibroblasts. Keratinocyte-derived MMP
      10 protein accumulated over time in the dermal compartment of organotypic
      cultures. TCDD-induced epidermal phenotypes in organotypic cultures were
      attenuated by the keratinocyte-specific expression of tissue inhibitor of
      metalloproteinase-1, a known inhibitor of MMP-10. These studies suggest that MMP
      10 and possibly other MMP-10-activated MMPs are responsible for the phenotypes
      exhibited in the basement membrane, the basal keratinocyte layer, and the
      cornified layer of TCDD-treated organotypic cultures. Our studies reveal a novel
      mechanism by which the epithelial-stromal microenvironment is altered in a tissue
      specific manner thereby inducing structural and functional pathology in the
      interfollicular epidermis of human skin. 

PMID- 24576723
TI  - In utero bisphenol A exposure disrupts germ cell nest breakdown and reduces
      fertility with age in the mouse.
AB  - Bisphenol A (BPA) is a known reproductive toxicant in rodents. However, the
      effects of in utero BPA exposure on early ovarian development and the
      consequences of such exposure on female reproduction in later reproductive life
      are unclear. Thus, we determined the effects of in utero BPA exposure during a
      critical developmental window on germ cell nest breakdown, a process required for
      establishment of the finite primordial follicle pool, and on female reproduction.
      Pregnant FVB mice (F0) were orally dosed daily with tocopherol-striped corn oil
      (vehicle), diethylstilbestrol (DES; 0.05 MUg/kg, positive control), or BPA (0.5,
      20, and 50 MUg/kg) from gestational day 11 until birth. Ovarian morphology and
      gene expression profiles then were examined in F1 female offspring on postnatal
      day (PND) 4 and estrous cyclicity was examined daily after weaning for 30 days.
      F1 females were also subjected to breeding studies with untreated males at three
      to nine months. The results indicate that BPA inhibits germ cell nest breakdown
      via altering expression of selected apoptotic factors. BPA also significantly
      advances the age of first estrus, shortens the time that the females remain in
      estrus, and increases the time that the females remain in metestrus and diestrus
      compared to controls. Further, F1 females exposed to low doses of BPA exhibit
      various fertility problems and have a significantly higher percentage of dead
      pups compared to controls. These results indicate that in utero exposure to low
      doses of BPA during a critical ovarian developmental window interferes with early
      ovarian development and reduces fertility with age.

PMID- 24576724
TI  - The chemopreventive activity of the histone deacetylase inhibitor tributyrin in
      colon carcinogenesis involves the induction of apoptosis and reduction of DNA
      damage.
AB  - The chemopreventive activity of the histone deacetylase inhibitor (HDACi)
      tributyrin (TB), a prodrug of butyric acid (BA), was evaluated in a rat model of
      colon carcinogenesis. The animals were treated with TB (TB group: 200mg/100g of
      body weight, b.w.) or maltodextrin (MD isocaloric control group: 300 mg/100g
      b.w.) daily for 9 consecutive weeks. In the 3rd and 4th weeks of treatment, the
      rats in the TB and MD groups were given DMH (40 mg/kg b.w.) twice a week. After 9
      weeks, the animals were euthanized, and the distal colon was examined. Compared
      with the control group (MD group), TB treatment reduced the total number of
      aberrant crypt foci (ACF; p<0.05) as well as the ACF with >=4 crypts (p<0.05),
      which are considered more aggressive, but not inhibited the formation of DMH
      induced O6-methyldeoxyguanosine DNA adducts. The TB group also showed a higher
      apoptotic index (p<0.05) and reduced DNA damage (p<0.05) compared with MD group.
      TB acted as a HDACi, as rats treated with the prodrug of BA had higher levels of
      histone H3K9 acetylation compared with the MD group (p<0.05). TB administration
      resulted in increased colonic tissue concentrations of BA (p<0.05) compared with
      the control animals. These results suggest that TB can be considered a promising
      chemopreventive agent for colon carcinogenesis because it reduced the number of
      ACF, including those that were more aggressive. Induction of apoptosis and
      reduction of DNA damage are cellular mechanisms that appear to be involved in the
      chemopreventive activity of TB.

PMID- 24576725
TI  - Inhibition of reactive oxygen species in hypothalamic paraventricular nucleus
      attenuates the renin-angiotensin system and proinflammatory cytokines in
      hypertension.
AB  - AIMS: To explore whether reactive oxygen species (ROS) scavenger (tempol) in the
      hypothalamic paraventricular nucleus (PVN) attenuates renin-angiotensin system
      (RAS) and proinflammatory cytokines (PICs), and decreases the blood pressure and
      sympathetic activity in angiotensin II (ANG II)-induced hypertension. METHODS AND
      RESULTS: Male Sprague-Dawley rats were infused intravenously with ANG II (10
      ng/kg per min) or normal saline (NS) for 4 weeks. These rats were treated with
      bilateral PVN infusion of oxygen free radical scavenger tempol (TEMP, 20 MUg/h)
      or vehicle (artificial cerebrospinal fluid, aCSF) for 4 weeks. ANG II infusion
      resulted in increased mean arterial pressure (MAP) and renal sympathetic nerve
      activity (RSNA). These ANG II-infused rats also had higher levels of gp91(phox)
      (a subunit of NAD(P)H oxidase), angiotensin-converting enzyme (ACE), and
      interleukin-1 beta (IL-1beta) in the PVN than the control animals. Treatment with
      PVN infusion of TEMP attenuated the overexpression of gp91(phox), ACE and IL
      1beta within the PVN, and decreased sympathetic activity and MAP in ANG II
      infused rats. CONCLUSION: These findings suggest that ANG II infusion induces
      elevated PICs and oxidative stress in the PVN, which contribute to the
      sympathoexcitation in hypertension. Inhibition of reactive oxygen species in
      hypothalamic paraventricular nucleus attenuates the renin-angiotensin system,
      proinflammatory cytokines and oxidative stress in ANG II-induced hypertension.

PMID- 24576727
TI  - Beware of the swinging pendulum: anti-tumor necrosis factor monotherapy vs
      combination therapy for inflammatory bowel disease.

PMID- 24576728
TI  - Reply: To PMID 23912083.

PMID- 24576726
TI  - Acute 7,12-dimethylbenz[a]anthracene exposure causes differential concentration
      dependent follicle depletion and gene expression in neonatal rat ovaries.
AB  - Chronic exposure to the polycyclic aromatic hydrocarbon 7,12
      dimethylbenz[a]anthracene (DMBA), generated during combustion of organic matter
      including cigarette smoke, depletes all ovarian follicle types in the mouse and
      rat, and in vitro models mimic this effect. To investigate the mechanisms
      involved in follicular depletion during acute DMBA exposure, two concentrations
      of DMBA at which follicle depletion has (75 nM) and has not (12.5 nM) been
      observed were investigated. Postnatal day four F344 rat ovaries were maintained
      in culture for four days before a single exposure to vehicle control (1% DMSO;
      CT) or DMBA (12 nM; low-concentration or 75 nM; high-concentration). After four
      or eight additional days of culture, DMBA-induced follicle depletion was
      evaluated via follicle enumeration. Relative to control, DMBA did not affect
      follicle numbers after 4 days of exposure, but induced large primary follicle
      loss at both concentrations after 8 days; while, the low-concentration DMBA also
      caused secondary follicle depletion. Neither concentration affected primordial or
      small primary follicle number. RNA was isolated and quantitative RT-PCR performed
      prior to follicle loss to measure mRNA levels of genes involved in xenobiotic
      metabolism (Cyp2e1, Gstmu, Gstpi, Ephx1), autophagy (Atg7, Becn1), oxidative
      stress response (Sod1, Sod2) and the phosphatidylinositol 3-kinase (PI3K) pathway
      (Kitlg, cKit, Akt1) 1, 2 and 4 days after exposure. With the exception of Atg7
      and cKit, DMBA increased (P < 0.05) expression of all genes investigated. Also,
      BECN1 and pAKT(Thr308) protein levels were increased while cKIT was decreased by
      DMBA exposure. Taken together, these results suggest an increase in DMBA
      bioactivation, add to the mechanistic understanding of DMBA-induced ovotoxicity
      and raise concern regarding female low concentration DMBA exposures.

PMID- 24576729
TI  - A rare cause of repeated gastrointestinal bleeding. Mesenteric cavernous
      lymphangioma.

PMID- 24576730
TI  - Iron deficiency in an HIV patient. Kaposi sarcoma.

PMID- 24576731
TI  - Masquerading gastrointestinal polyps: air on the side of caution? Cystic
      pneumatosis.

PMID- 24576732
TI  - Identification of NTCP as an HBV receptor: the beginning of the end or the end of
      the beginning?

PMID- 24576733
TI  - An incidental subepithelial mass in the esophagus. Lymphoepithelioma-like
      carcinoma appearing as a subepithelial tumor in the esophagus.

PMID- 24576734
TI  - Dietary fiber intake and Crohn's disease.

PMID- 24576735
TI  - Dietary fiber and risk of inflammatory bowel disease: fact or hype?

PMID- 24576736
TI  - A duodenal tumor with intermittent obstruction. Brunner's gland hyperplasia.

PMID- 24576737
TI  - Reply: To PMID 23891975.

PMID- 24576738
TI  - Have we overestimated the risk of lymphoma associated with thiopurine treatment
      for ulcerative colitis?

PMID- 24576739
TI  - Intermittent esophageal dysphagia: an intriguing diagnosis. Dysphagia lusoria.

PMID- 24576741
TI  - Comparing plasma concentrations of persistent organic pollutants and metals in
      primiparous women from northern and southern Canada.
AB  - The exposure of Aboriginal peoples in the Canadian Arctic to persistent organic
      pollutants (POPs) and metals through the consumption of traditional food items is
      well recognized; however, less information is available for Canadian immigrants.
      The direct comparison of blood chemical concentrations for expectant primiparous
      women sampled in the Inuvik and Baffin regions of the Canadian Arctic, as well as
      Canadian- and foreign-born women from five southern Canadian centers (Halifax,
      Vancouver, Hamilton, Ottawa, and Calgary), provides relative exposure information
      for samples of northern and southern mothers in Canada. Based on our analyses,
      Canadian mothers are exposed to a similar suite of contaminants; however, Inuit
      first birth mothers residing in the Canadian Arctic had higher age-adjusted
      geometric mean concentrations for several legacy POPs regulated under the
      Stockholm Convention, along with lead and total mercury. Significant differences
      in exposure were observed for Inuit mothers from Baffin who tended to demonstrate
      higher blood concentrations of POPs and total mercury compared with Inuit mothers
      from Inuvik. Conversely, northern mothers showed a significantly lower age
      adjusted geometric mean concentration for a polybrominated diphenyl ether (PBDE
      153) compared to southern mothers. Furthermore, southern Canadian mothers born
      outside of Canada showed the highest individual concentrations measured in the
      study: 1700 MUg/kg lipids for p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE)
      and 990 MUg/kg lipids for beta-hexachlorocyclohexane (beta-HCH). Data from Cycle
      1 (2007-2009) of the nationally-representative Canadian Health Measures Survey
      (CHMS) places these results in a national biomonitoring context and affirms that
      foreign-born women of child-bearing age experience higher exposures to many POPs
      and metals than their Canadian-born counterparts in the general population.

PMID- 24576740
TI  - Osthole attenuates the development of carrageenan-induced lung inflammation in
      rats.
AB  - Osthole has been reported to possess a variety of pharmacological activities,
      such as antiinflammatory effect. In the present study, we have investigated the
      effect of osthole on lung inflammation associated with carrageenan-induced
      pleurisy in rats. The result showed that osthole could inhibit significantly
      pleural exudates formation and PMNs infiltration. Histological examination
      revealed osthole could reduce lung inflammation in rats treated with carrageenan.
      The myeloperoxidase (MPO) level was examined in pleural exudates. The result
      showed that osthole could attenuate MPO level in pleural exudates. Further
      studies showed osthole could decrease tumor necrosis factor alpha (TNF-alpha) and
      interleukin 1beta (IL-1beta) levels in the lungs. Taken together, the present
      results suggested that osthole could inhibit lung inflammation on carrageenan
      induced pleurisy in rats and that could be related to a reduction of PMNs
      infiltration and release of inflammatory factors. 

PMID- 24576742
TI  - Large scale meta-analysis of urinary C-terminal telopeptide, serum cartilage
      oligomeric protein and matrix metalloprotease degraded type II collagen and their
      role in prevalence, incidence and progression of osteoarthritis.
AB  - OBJECTIVE: To evaluate the role of three cartilage-derived biomarkers on
      osteoarthritis (OA): urinary C-terminal telopeptide (uCTX-II), serum cartilage
      oligomeric protein (sCOMP), and serum MMP degraded type II collagen (sC2M).
      SUBJECTS AND METHODS: Samples from 3582 individuals from the Rotterdam Study, the
      Genetics osteoArthritis and Progression (GARP), the Chingford Study and the
      TwinsUK cohort were assayed using enzyme-linked immune sorbent assays. Log10 of
      concentration levels were correlated with risk of hip, hand and knee OA, hip and
      knee OA severity and incidence, and progression of knee OA, adjusting for age,
      gender and body mass index (BMI). Results were meta-analysed to assess overall
      significance. RESULTS: After adjusting for covariates, sCOMP was associated with
      knee OA and hip and knee OA incidence. Furthermore, sC2M was associated with knee
      OA incidence and progression. After adjustment for multiple tests (Bonferroni P <
      0.002) only the association between sCOMP and knee OA remained significant (odds
      ratio (OR) = 3.26 (95%CI 1.63-10.1) P = 0.0008 for each standard deviation (SD)
      increase in biomarker levels). Levels of uCTX-II were significantly associated
      with risk of hand, hip and knee OA, progression and incidence of knee OA. A
      receiver operating characteristics (ROC) analysis showed a consistent improvement
      in prediction of knee OA progression from an average area under the curve (AUC)
      is 0.646 for age, sex and BMI alone to an AUC = 0.668 including uCTX-II for
      prediction. CONCLUSIONS: uCTX-II is the most informative biochemical marker for
      prediction of OA. Both sCOMP and C2M showed some association with OA, thus
      indicating that they are descriptive of disease activity.

PMID- 24576743
TI  - Funnel tenotomy versus intracuff tenodesis for lesions of the long head of the
      biceps tendon associated with rotator cuff tears.
AB  - BACKGROUND: There is no clear consensus regarding optimal management of lesions
      of the long head of the biceps tendon (LHBT) associated with rotator cuff tears.
      PURPOSE: To compare clinical outcome and cosmetic deformity of a funnel tenotomy
      versus intracuff tenodesis for concomitant LHBT lesion in patients with rotator
      cuff tears. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Patients
      who underwent surgical treatment for rotator cuff tears associated with LHBT
      lesions between March 2005 and February 2011 were enrolled in the study (N = 83).
      Forty-one underwent a funnel tenotomy (group A), and 42 underwent an intracuff
      tenodesis (group B). The mean age at the time of operation was 63.8 years in
      group A (range, 44-68 years) and 58.6 years in group B (range, 45-70 years).
      RESULTS: At the most recent follow-up, the mean University of California at Los
      Angeles (UCLA) score in group A improved from a preoperative mean of 16.9 +/- 3.6
      to 30.6 +/- 4.1 (P < .001), and the Constant score improved from 58.7 +/- 14.2 to
      73.8 +/- 11.2 (P < .001). In group B, these scores improved from 18.1 +/- 4.0 to
      31.3 +/- 3.0 (P < .001) and 53.6 +/- 13.4 to 74.8 +/- 11.9 (P < .001),
      respectively. There were no statistically significant differences between the 2
      groups (P = .43 for UCLA, P = .81 for Constant score). Popeye deformity was
      detected in 11 cases of group A (26.8%) and in 7 cases of group B (16.7%) (P =
      .06). CONCLUSION: For the treatment of concomitant LHBT lesions in patients with
      rotator cuff tears, both a funnel tenotomy and an intracuff tenodesis showed good
      clinical outcomes. Even though the incidence of Popeye deformity in the funnel
      tenotomy group tended to be higher, there was no significant difference in the
      overall incidence of cosmetic deformity between the 2 groups.

PMID- 24576744
TI  - Inferior suture anchor placement during arthroscopic Bankart repair: influence of
      portal placement and curved drill guide.
AB  - BACKGROUND: During arthroscopic Bankart repair, inferior anchor placement is
      critical to a successful outcome. Low anterior anchors may be placed with a
      standard straight guide via midglenoid portal, with a straight guide with trans
      subscapularis placement, or with curved guide systems. Purpose/ HYPOTHESIS: To
      evaluate glenoid suture anchor trajectory, position, and biomechanical
      performance as a function of portal location and insertion technique. It is
      hypothesized that a trans-subscapularis portal or curved guide will improve
      anchor position, decrease risk of opposite cortex breach, and confer improved
      biomechanical properties. STUDY DESIGN: Controlled laboratory study. METHODS:
      Thirty cadaveric shoulders were randomized to 1 of 3 groups: straight guide,
      midglenoid portal (MG); straight guide, trans-subscapularis portal (TS); and
      curved guide, midglenoid portal (CG). Three BioRaptor PK 2.3-mm anchors were
      inserted arthroscopically, with an anchor placed at 3, 5, and 7 o'clock.
      Specimens were dissected with any anchor perforation of the opposite cortex
      noted. An "en face" image was used to evaluate actual anchor position on a
      clockface scale. Each suture anchor underwent cyclic loading (10-60 N, 250
      cycles), followed by a load-to-failure test (12.5 mm/s). Fisher exact test and
      mixed effects regression modeling were used to compare outcomes among groups.
      RESULTS: Anchor placement deviated from the desired position by 9.9 degrees  +/-
      11.4 degrees  in MG specimens, 11.1 degrees  +/- 13.8 degrees  in TS, and 13.1
      degrees  +/- 14.5 degrees  in CG. After dissection, opposite cortex perforation
      at 5 o'clock occurred in 50% of MG anchors, 0% of TS, and 40% of CG. Of the 90
      anchors tested, 17 (19%) failed during cyclic loading, with a similar failure
      rate across groups (P = .816). The maximum load was significantly higher for the
      3-o'clock anchors when compared with the 5-o'clock anchors, regardless of portal
      or guide (P = .021). For the 5-o'clock position, there were significantly fewer
      "out" anchors in the TS group versus the CG or MG group (P = .038). There was no
      statistically significant difference in maximum load among groups at 5 o'clock.
      CONCLUSION: Accuracy in suture anchor placement during arthroscopic Bankart
      repair can vary depending on both portal used and desired position of anchor. The
      results of the current study indicate that there was no difference in ultimate
      load to failure among anchors inserted via a midglenoid straight guide,
      midglenoid curved guide, or percutaneous trans-subscapularis approach. However,
      midglenoid portal anchors drilled with a straight or curved guide and placed at
      the 5-o'clock position had significant increased risk of opposite cortex
      perforation compared with trans-subscapularis percutaneous insertion, with no
      apparent biomechanical detriment. CLINICAL RELEVANCE: The findings from this
      study will facilitate improved understanding of risks and benefits of several
      techniques for arthroscopic shoulder instability treatment with regard to suture
      anchor fixation.

PMID- 24576745
TI  - Loss/retention and evolution of NBS-encoding genes upon whole genome triplication
      of Brassica rapa.
AB  - A genome triplication took place in the ancestor of Brassiceae species after the
      split of the Arabidopsis lineage. The postfragmentation and shuffling of the
      genome turned the ancestral hexaploid back to diploids and caused the radiation
      of Brassiceae species. The course of speciation was accompanied by the loss of
      duplicate genes and also influenced the evolution of retained genes. Of all the
      genes, those encoding NBS domains are typical R genes that confer resistance to
      invading pathogens. In this study, using the genome of Arabidopsis thaliana as a
      reference, we examined the loss/retention of orthologous NBS-encoding loci in the
      tripled Brassica rapa genome and discovered differential loss/retention
      frequencies. Further analysis indicated that loci of different retention ratios
      showed different evolutionary patterns. The loci of classesII and III
      (maintaining two and three syntenic loci, respectively, multi-loci) show sharper
      expansions by tandem duplications, have faster evolutionary rates and have more
      potential to be associated with novel gene functions. On the other hand, the loci
      that are retained at the minimal rate (keeping only one locus, class I, single
      locus) showed opposite patterns. Phylogenetic analysis indicated that
      recombination and translocation events were common among multi-loci in B. rapa,
      and differential evolutionary patterns between multi- and single-loci are likely
      the consequence of recombination. Investigations towards other gene families
      demonstrated different evolutionary characteristics between different gene
      families. The evolution of genes is more likely determined by the property of
      each gene family, and the whole genome triplication provided only a specific
      condition. 

PMID- 24576746
TI  - Increased plasma levels of BDNF and inflammatory markers in Alzheimer's disease.
AB  - Alzheimer's disease (AD) is the most common cause of dementia in the elderly.
      Neurotrophic factors and inflammatory markers may play considerable roles in AD.
      In this study we measured, through Enzyme-Linked Immunosorbent Assay, the plasma
      levels of brain derived neurotrophic factor (BDNF), glial cell-derived
      neurotrophic factor (GDNF) and neuronal growth factor (NGF), as well as tumor
      necrosis factor-alpha soluble receptors, sTNFR1 and sTNFR2, and soluble
      intercellular adhesion molecule 1 (sICAM-1), in 50 AD patients, 37 patients with
      mild cognitive impairment (MCI) and 56 healthy elderly controls. BDNF levels,
      expressed as median and interquartile range, were higher for AD patients (2545.3,
      1497.4-4153.4 pg/ml) compared to controls (1503.8, 802.3-2378.4 pg/ml), P <
      0.001. sICAM-1 was also higher in AD patients. sTNFR1 levels were increased in AD
      when compared to controls and also to MCI. GDNF, NGF and sTNFR2 levels showed no
      significant differences among the studied groups. The increase in BDNF might
      reflect a compensatory mechanism against early neurodegeneration and seems to be
      related to inflammation. sTNFR1 appears to mark not only the inflammatory state
      but also differentiates between MCI and AD, which may be an additional tool for
      differentiating degrees of cognitive impairment. 

PMID- 24576747
TI  - Learning using privileged information: SVM+ and weighted SVM.
AB  - Prior knowledge can be used to improve predictive performance of learning
      algorithms or reduce the amount of data required for training. The same goal is
      pursued within the learning using privileged information paradigm which was
      recently introduced by Vapnik et al. and is aimed at utilizing additional
      information available only at training time-a framework implemented by SVM+. We
      relate the privileged information to importance weighting and show that the prior
      knowledge expressible with privileged features can also be encoded by weights
      associated with every training example. We show that a weighted SVM can always
      replicate an SVM+ solution, while the converse is not true and we construct a
      counterexample highlighting the limitations of SVM+. Finally, we touch on the
      problem of choosing weights for weighted SVMs when privileged features are not
      available. 

PMID- 24576748
TI  - [Transanal total mesorectal excision].

PMID- 24576749
TI  - Measuring the spatial extent of texture pooling using reverse correlation.
AB  - The local image representation produced by early stages of visual analysis is
      uninformative regarding spatially extensive textures and surfaces. We know little
      about the cortical algorithm used to combine local information over space, and
      still less about the area over which it can operate. But such operations are
      vital to support perception of real-world objects and scenes. Here, we deploy a
      novel reverse-correlation technique to measure the extent of spatial pooling for
      target regions of different areas placed either in the central visual field, or
      more peripherally. Stimuli were large arrays of micropatterns, with their
      contrasts perturbed individually on an interval-by-interval basis. By comparing
      trial-by-trial observer responses with the predictions of computational models,
      we show that substantial regions (up to 13 carrier cycles) of a stimulus can be
      monitored in parallel by summing contrast over area. This summing strategy is
      very different from the more widely assumed signal selection strategy (a MAX
      operation), and suggests that neural mechanisms representing extensive visual
      textures can be recruited by attention. We also demonstrate that template
      resolution is much less precise in the parafovea than in the fovea, consistent
      with recent accounts of crowding. 

PMID- 24576750
TI  - Attenuation of S-cone function at high altitude assessed by electroretinography.
AB  - As impaired S-cone function has been reported psychophysically this study
      assessed S-cone function during high altitude exposure using electroretinography
      (ERG) and investigated a possible association with severity of acute mountain
      sickness (AMS). This work is related to the Tubingen High Altitude Ophthalmology
      (THAO) study. Standard ERG equipment was used (Diagnosys LLC, Cambridge, UK) with
      special protocol settings to extract S-cone function. Twelve subjects were
      analyzed in the current study and examinations were performed in Tubingen,
      Germany (341m) as baseline and thereafter at the Capanna Margherita, Italy
      (4559m) at high altitude. Results were compared using a paired t-test.
      Correlations between ERG measurements and oxygen saturation (SpO2), heart rate
      (HR) and scores of acute mountain sickness (AMS-C and LL) were calculated using
      Pearson's correlation coefficients. Amplitudes of S-cone b-waves decreased
      significantly at high altitude (p=0.02). No significant changes were observed for
      implicit times of b-waves (p=0.63), a-waves (p=0.75) or for a-wave amplitudes
      (p=0.78). The incidence of AMS was 50% at high altitude according to AMS-C and LL
      scores (AMS-C?0.7 and LL?5). Heart rate increased to 84+/-10min(-1) and SpO2
      decreased to 71.9+/-5.7% at high altitude. No significant correlation was found
      between S-cone ERG parameters and SpO2, HR, AMS-C and LL. For the first time our
      study defines a significant impairment of S-cone function at high altitude time
      using objective state of the art examination methods. No correlation between the
      functional impairment of S-cones and levels of AMS was detected. 

PMID- 24576751
TI  - Pins and rubber band traction for treatment of comminuted intra-articular
      fractures in the hand.
AB  - PURPOSE: To determine the efficacy of pins and rubber band traction for treatment
      of comminuted intra-articular fractures in the hand. METHODS: We performed a
      retrospective study from 1994 to 2013 to evaluate 33 patients in whom pins and
      rubber band traction was employed. We clinically evaluated the active range of
      motion of the affected fingers after surgery. Eleven of the 33 fractures were at
      the proximal interphalangeal joint, 10 at the distal interphalangeal joint, 5 at
      the thumb interphalangeal joint, and 2 at the metacarpophalangeal joint of the
      thumb. The remaining 5 patients had complex fracture-dislocation of the proximal
      interphalangeal joints. RESULTS: The mean follow-up period was 24 months. The
      average active motion of the metacarpophalangeal joints of the fingers was 91
      degrees  (range, extension 0 degrees -10 degrees /flexion 85 degrees -90 degrees
      ), proximal interphalangeal joints was 92 degrees  (range, extension/flexion 0
      degrees -10 degrees /85 degrees -100 degrees ), and distal interphalangeal joints
      was 73 degrees  (range, extension/flexion 0 degrees -10 degrees /60 degrees -80
      degrees ). The overall average of all active motion of the injured fingers except
      thumbs was 255 degrees  (range, 240 degrees -270 degrees ). The average active
      motion of the of the thumb metacarpophalangeal joint was 56 degrees  (range,
      extension 5 degrees -10 degrees /flexion 50 degrees -55 degrees ), and
      interphalangeal joint was 74 degrees  (range, extension 0 degrees -10 degrees
      /flexion 75 degrees -80 degrees ). The average of active motion of the injured
      thumb metacarpal and interphalangeal joints combined was 130 degrees  (range, 125
      degrees -135 degrees ). CONCLUSIONS: Pins and rubber band traction is a treatment
      option for comminuted displaced intra-articular fractures of the digits that
      offers satisfactory clinical results. TYPE OF STUDY/LEVEL OF EVIDENCE:
      Therapeutic IV.

PMID- 24576752
TI  - The effect of distal radius translation in the coronal plane on forearm rotation:
      a cadaveric study of distal radius fractures.
AB  - PURPOSE: To determine the effect of lateral translation of the distal radius in
      the coronal plane on forearm rotation after distal radius fracture. METHODS: Ten
      fresh cadaveric limbs underwent distal radius osteotomy just proximal to the
      distal radial-ulnar joint to simulate an extra-articular distal radius fracture.
      We used an Agee Wrist Jack external fixator to create increasing magnitudes of
      distal fragment lateral translation in 2-mm increments. Forearm rotation was
      measured using a 3-dimensional camera at each magnitude of lateral translation.
      RESULTS: Total forearm rotation for the intact specimen and 2, 4, 6, and 8 mm
      (maximal) radial translations was 186 degrees  +/- 53 degrees , 188 degrees  +/-
      54 degrees , 189 degrees  +/- 55 degrees , 190 degrees  +/- 57 degrees , and 193
      degrees  +/- 59 degrees , respectively. There was no significant difference for
      any magnitude of radial translation. The average maximal radial translation
      possible before radioulnar abutment was 8 +/- 0.5 mm. CONCLUSIONS: In this
      cadaveric model, translation of the distal radius fragment in the lateral
      direction had no effect on forearm rotation. CLINICAL RELEVANCE: At the level of
      the proximal border of the distal radioulnar joint, isolated distal radius
      translation does not significantly affect forearm rotation.

PMID- 24576753
TI  - Clinical efficacy of a fragility care program in distal radius fracture patients.
AB  - PURPOSE: To assess the quality of an initiative to improve the diagnosis and
      management of osteoporosis in patients over 50 years of age with distal radius
      fractures (DRF). METHODS: A retrospective review was conducted to determine the
      baseline percentage of individuals undergoing osteoporosis screening after DRF.
      Thereafter, a study was implemented in which DRF patients who were not being
      treated for osteoporosis or had not recently undergone screening were offered a
      dual-energy x-ray absorptiometry scan and referral to endocrinology at the
      initial hand surgery clinic visit. Patients who declined participation were
      contacted by a patient educator to discuss the benefits of screening and address
      their concerns. Those who then wanted to receive an osteoporosis evaluation were
      scheduled for bone scanning and endocrinology consultation. RESULTS: During the
      baseline period, 7 patients (15%) were screened, and 41 (85%) were not screened.
      During the active phase of the initiative, 82 patients over 50 years of age were
      treated for a DRF at our institution. A total of 44 patients were identified for
      potential osteoporosis screening, and 35 patients met inclusion criteria. Of
      these, 19 (54%) agreed to screening after the initial orthopedic evaluation, and
      16 declined. After speaking to a patient educator, 9 of these 16 patients agreed
      to screening. Of the remaining 7 patients, 4 again declined screening and 3 were
      unavailable by telephone. Overall, 80% of patients who were identified in the
      initiative agreed to osteoporosis screening after the combination of
      recommendation during hand surgery clinic visit and patient education by
      telephone, and 64% were diagnosed with osteoporosis/osteopenia as a result of
      completing screening. CONCLUSIONS: An integrated model of care among orthopedic
      surgeons, patient educators, and endocrinologists substantially increased
      screening for osteoporosis after DRF. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic
      II.

PMID- 24576754
TI  - A systematic review of 2-strand versus multistrand core suture techniques and
      functional outcome after digital flexor tendon repair.
AB  - PURPOSE: To determine published evidence to evaluate the hypothesis that
      multistrand techniques result in a poorer outcome than 2-strand techniques for
      digital flexor tendon repairs. METHODS: A systematic review was undertaken to
      compare outcomes and rupture rates between 2-strand and multistrand core sutures
      in digital flexor zones 2 to 5. Outcome was measured by the American Society for
      Surgery of the Hand criteria, original or modified Strickland criteria, or Buck
      Gramcko criteria. RESULTS: A total of 1,878 patients (2,585 digits; 3,749
      tendons) were included from the selected studies. Thirty-three studies reported 2
      strand repairs and 15 reported multistrand repairs. Of the total tendon injuries,
      59% were flexor digitorum profundus, 38% were flexor digitorum superficialis, and
      2% were flexor pollicis longus. The pooled rupture rate was 3.9 per 100 digits.
      No significant difference was detected between 2-strand and multistrand repairs
      for outcomes by all measures or rupture rate. CONCLUSIONS: Because of the wide
      variation in reporting of outcomes and study design on which this analysis was
      based, we cannot definitively confirm our hypothesis. We present the standards
      for outcomes as well as rupture rate for digital flexor tendon repair. TYPE OF
      STUDY/LEVEL OF EVIDENCE: Therapeutic III.

PMID- 24576755
TI  - Treatment of painful median nerve neuromas with radial and ulnar artery
      perforator adipofascial flaps.
AB  - PURPOSE: To review the outcomes of 8 patients with painful median nerve neuromas
      at the wrist treated with external neurolysis and covered with pedicled
      perforator adipofascial flaps. METHODS: Between 2004 and 2010, we treated 8
      patients, who had a mean age of 37 years, and who had posttraumatic painful
      median nerve neuromas at the level of the wrist but with retained median nerve
      function . All of them reported neuropathic pain and had a positive Tinel's sign
      over the site of the presumed neuroma. The surgical procedure included external
      neurolysis and coverage with an ulnar artery perforator adipofascial flap (4
      patients) or with a radial artery perforator adipofascial flap (4 patients).
      Patients were reviewed after a mean follow-up of 41 months (range, 18-84 mo).
      Preoperative and postoperative pain was measured with a visual analog scale.
      RESULTS: Pain improved from a preoperative mean value of 7.8 to a postoperative
      mean value of 3.6. There was complete resolution of pain in 5 patients, mild pain
      persisted in 2 patients, and 1 patient reported no improvement. No complications
      occurred at the donor site. CONCLUSIONS: Vascularized soft tissue coverage of
      painful median nerve neuromas is an effective treatment. We do not believe that a
      free flap is of any particular advantage over a local pedicle flap which we
      suggest using to protect the median nerve. TYPE OF STUDY/LEVEL OF EVIDENCE:
      Therapeutic IV.

PMID- 24576756
TI  - Dissatisfaction after trapezial-metacarpal arthroplasty.

PMID- 24576757
TI  - Muscle transfer to restore elbow flexion.

PMID- 24576758
TI  - Distinct biochemical activities and heat shock responses of two UDP-glucose
      sterol glucosyltransferases in cotton.
AB  - UDP-glucose sterol glucosyltransferase (SGT) are enzymes typically involved in
      the production of sterol glycosides (SG) in various organisms. However, the
      biological functions of SGTs in plants remain largely unknown. In the present
      study, we identified two full-length GhSGT genes in cotton and examined their
      distinct biochemical properties. Using UDP-[U-(14)C]-glucose and beta-sitosterol
      or total crude membrane sterols as substrates, GhSGT1 and GhSGT2 recombinant
      proteins were detected with different enzymatic activities for SG production. The
      addition of Triton (X-100) strongly inhibited the activity of GhSGT1 but caused
      an eightfold increase in the activity of GhSGT2. The two GhSGTs showed distinct
      enzyme activities after the addition of NaCl, MgCl2, and ZnCl2, indicating that
      the two GhSGTs exhibited distinct biochemical properties under various
      conditions. Furthermore, after heat shock treatment, GhSGT1 showed rapidly
      enhanced gene expression in vivo and low enzyme activity in vitro, whereas GhSGT2
      maintained extremely low gene expression levels and relatively high enzyme
      activity. Notably, the GhSGT2 gene was highly expressed in cotton fibers, and the
      biochemical properties of GhSGT2 were similar to those of GhCESA in favor for
      MgCl2 and non-reduction reaction condition. It suggested that GhSGT2 may have
      important functions in cellulose biosynthesis in cotton fibers, which must be
      tested in the transgenic plants in the future. Hence, the obtained data provided
      insights into the biological functions of two different GhSGTs in cotton and in
      other plants.

PMID- 24576759
TI  - Alleviation of methyl viologen-mediated oxidative stress by Brassica juncea
      annexin-3 in transgenic Arabidopsis.
AB  - Plant annexins function as calcium-dependent or -independent phospholipid binding
      proteins and constitute about 0.1% of total cellular proteins. Some of them were
      reported to antagonize oxidative stress and protect plant cells. Brassica juncea
      annexin-3 (AnnBj3) was recently discovered. To gain insight into a possible
      function of AnnBj3 in oxidative stress response, we investigated the resistance
      of Arabidopsis thaliana plants expressing AnnBj3 constitutively. Here we report
      that, AnnBj3 attenuates methyl viologen-mediated oxidative stress in plants. It
      protected photosynthesis and plasma membrane from methyl viologen-mediated
      oxidative damage. AnnBj3 detoxifies hydrogen peroxide and showed antioxidative
      property in vitro. The protein increased total peroxidase activity in transgenics
      and interfered with other cellular antioxidants, thereby giving an overall
      cellular protection against methyl viologen-induced cytotoxicity.

PMID- 24576760
TI  - Lipase activity and antioxidant capacity in coffee (Coffea arabica L.) seeds
      during germination.
AB  - In this paper, lipase activity was characterized in coffee (Coffea arabica L.)
      seeds to determine its involvement in lipid degradation during germination. The
      lipase activity, evaluated by a colorimetric method, was already present before
      imbibition of seeds and was further induced during the germination process. The
      activity showed a biphasic behaviour, which was similar in seeds either with or
      without endocarp (parchment), even though the phenomenon showed a delay in the
      former. The enzymatic activity was inhibited by tetrahydrolipstatin (THL), a
      selective and irreversible inhibitor of lipases, and by a polyclonal antibody
      raised against purified alkaline lipase from castor bean. The immunochemical
      analysis evidenced a protein of ca. 60 kDa, cross-reacting with an anti-lipase
      antibody, in coffee samples obtained from seeds of both types. Gas
      chromatographic analyses of free fatty acid (FFA) content confirmed the
      differences shown in the lipolytic activity of the samples with or without
      parchment, since FFA levels increased more rapidly in samples without parchment.
      Finally, the analyses of the antioxidant capacity showed that the presence of
      parchment was crucial for lowering the oxidation of the lipophylic fraction,
      being the seeds with parchment less prone to oxidation processes.

PMID- 24576761
TI  - Removal of DELLA repression promotes leaf senescence in Arabidopsis.
AB  - Leaf senescence is an integrated response of leaf cells to developmental age and
      various internal and environmental signals. However, the role of gibberellins
      (GA) in leaf senescence is not clear. In the current study, we investigated the
      effect of DELLA on leaf senescence. Compared with the wild type (WT), leaf
      senescence occurred earlier in the mutant ga1-3 gai-t6 rga-t2 rgl1-1 rgl2-1
      (abbreviated as Q-DELLA/ga1-3) whose DELLA repression was removed, whereas leaf
      senescence was retarded in the mutant ga1-3 whose GA biosynthesis was blocked and
      whose DELLA proteins accumulated abnormally. During leaf senescence, SAG12 and
      SAG29 were upregulated in Q-DELLA/ga1-3 and downregulated in ga1-3 plants. The Q
      DELLA/ga1-3 senescent leaves contained more sugar but less chlorophyll and fatty
      acids (FAs) than those of ga1-3 and WT. Both absolute and relative contents of
      C18:3 in Q-DELLA/ga1-3 senescent leaves were lower compared with those of the WT
      and ga1-3 leaves. The genes regulating FA beta-oxidation in Q-DELLA/ga1-3, such
      as KAT2, LACS6, LACS7, ACX1, ACX2 and MAP2, were significantly upregulated. The
      removal of DELLA repression highly upregulated certain genes on various hormone
      pathways, suggesting that GA signaling acts upstream of the jasmonic acid,
      salicylic acid, and ethylene pathways in regulating leaf senescence.

PMID- 24576762
TI  - Influence of the temporal and spatial variation of nitrate reductase, glutamine
      synthetase and soil composition in the N species content in lettuce (Lactuca
      sativa).
AB  - The variation of nitrate reductase (NR), glutamine synthetase (GS) and N content
      in lettuce was evaluated at 5 stages of lettuce growth. Soil physicochemical
      properties and its N content were also assessed to elucidate the soil-to-plant
      transfer of inorganic N and potential leaching to groundwater. A decrease of NR
      activity and an increase of NO3(-) and N-Kjeldahl content in lettuces were
      observed during plant growth, whereas GS activity and NH4(+) increased during the
      first few weeks of lettuce growth and then decreased. Although the temporal
      variation was similar in lettuces grown in different soils, quantitative
      differences were observed, indicating that high NO3(-) content in soil caused a
      higher NO3(-) accumulation in lettuce despite the higher NR activity during the
      initial stage of plant growth. Higher levels of NO3(-) and NH4(+) were correlated
      with higher levels of N-Kjeldahl in lettuce suggesting a positive effect of these
      N species in the biosynthesis of organic forms of N. Soil physicochemical
      properties influenced the mobility of inorganic N within the groundwater-soil
      plant system. Sandy soils with low OM content allowed NO3(-) leaching, which was
      confirmed by higher NO3(-) levels in groundwater. Therefore, lettuces grown in
      those soils presented lower N content and the inputs of N to the environment were
      higher. 

PMID- 24576763
TI  - Modification of the degree of 4-O-methylation of secondary wall glucuronoxylan.
AB  - Plant secondary walls are the major constituent of plant biomass targeted for
      second-generation biofuel production. Therefore, a thorough understanding of how
      secondary walls are constructed is critical for a better utilization of plant
      biomass for biofuel production. One of the major components in secondary walls is
      xylan, which is composed of a linear chain of beta-1,4-linked xylosyl residues.
      In Arabidopsis, about 10% of xylosyl residues in xylan are substituted with
      glucuronic acid (GlcA), of which 60% are methylated at O-4. By contrast, all of
      the GlcA substituents in Populus xylan are methylated at O-4. It is not known how
      the degree of GlcA methylation in xylan is controlled. In this report, we
      demonstrated that simultaneous T-DNA knockout mutations of the three
      glucuronoxylan methyltransferase (GXM) genes, GXM1, GXM2, and GXM3/GXMT1, which
      are specifically expressed in secondary wall-forming cells, led to a complete
      loss of GlcA methylation in xylan in Arabidopsis stems. Overexpression of GXM2
      and GXM3 in wild-type Arabidopsis resulted in an up to 5-fold increase in
      glucuronoxylan methyltransferase activity and as a result, up to 90% of the GlcA
      side chains in xylan were methylated as opposed to 60% seen in the wild type. The
      increased degree of GlcA methylation in xylan had no discernable effects on cell
      wall sugar composition and lignin monomer composition. These results reveal that
      the activities of GXM1, GXM2 and GXM3 are responsible for all of the GlcA
      methylation in xylan in Arabidopsis stems and that the degree of GlcA methylation
      in xylan can be modified by altered expression of GXMs.

PMID- 24576764
TI  - Transcriptional circuitry underlying seed coat development in Arabidopsis.
AB  - We analyzed two sub-regions of the maternal seed coat, chalazal (CZSC) and distal
      (SC), using transcriptomic and histological analyses in the model plant
      Arabidopsis thaliana. Hierarchical clustering analysis showed that the CZSC and
      SC are transcriptionally distinct, though the two sub-regions are more similar
      during early stages of seed development. Robust statistical and network analysis
      revealed novel roles for both sub-regions during the course of the seed lifecycle
      and provides insight into the regulatory circuitry underlying these poorly
      studied sub-regions of the seed. Data show many of the processes that
      characterize the SC including starch deposition during the morphogenesis phase,
      and mucilage deposition and cell wall thickening during the maturation phase, are
      either absent or expressed to a much lesser extent in the CZSC. We further
      analyzed the CZSC in detail and show that this sub-region is likely involved in
      the control of information into the seed from the maternal plant and that some of
      these processes are predicted to operate through the activity of bZIP
      transcription factors through the G-box DNA sequence motif.

PMID- 24576765
TI  - Ferulic acid 5-hydroxylase 1 is essential for expression of anthocyanin
      biosynthesis-associated genes and anthocyanin accumulation under photooxidative
      stress in Arabidopsis.
AB  - Anthocyanins are important for preventing photoinhibition and photodamage. By
      comprehensive reverse genetic analysis of chloroplast-produced H2O2-responsive
      genes, we isolated here an anthocyanin-deficient mutant under photooxidative
      stress, which lacked ferulate 5-hydroxylase 1 (FAH1) involved in the
      phenylpropanoid pathway. Interestingly, the expression of anthocyanin
      biosynthesis-associated genes was also inhibited in this mutant. These findings
      suggest that FAH1 is essential for expression of anthocyanin biosynthesis
      associated genes and anthocyanin accumulation under photooxidative stress in
      Arabidopsis. Furthermore, we found that estrogen-inducible silencing of thylakoid
      membrane-bound ascorbate peroxidase, which is a major H2O2-scavenging enzyme in
      chloroplasts, enhances the expression of FAH1 and anthocyanin biosynthesis
      associated genes and accumulation of anthocyanin without any application of
      stress. Thus, it is likely that chloroplastic H2O2 activates FAH1 expression to
      induce anthocyanin accumulation for protecting cells from photooxidative stress.

PMID- 24576766
TI  - In vivo laser scanning confocal microscopy of the ocular surface in glaucoma.
AB  - Over the past decade, knowledge about the ocular surface in glaucoma has
      significantly increased through the use of in vivo laser scanning confocal
      microscopy (LSCM). This in vivo imaging method can show modifications at the
      cellular level induced by anti-glaucoma drugs on ocular surface structures and
      adnexa in the eye. High-quality images of the conjunctiva, cornea, limbus,
      meibomian glands, and lymphoid structures during therapy can be obtained. In
      addition, LSCM opened new fields of research on the patho-physiology of aqueous
      humor (AH) hydrodynamics in untreated, and in medically or surgically treated
      glaucomatous patients. In these conditions, an enhancement of the trans-scleral
      AH outflow contributed to clarification of the mechanism of action of different
      anti-glaucoma medications and surgical approaches. Finally, the use of LSCM
      represented a huge advance in evaluation of bleb functionality after filtration
      surgery, defining the hallmarks of AH filtration through the bleb-wall and
      distinguishing functional from nonfunctional blebs. Thus, signs seen with LSCM
      may anticipate clinical failure, guiding the clinician in planning the
      appropriate timing of the various steps in bleb management. In this review we
      summarize the current knowledge about in vivo LSCM of the ocular surface in
      glaucoma. 

PMID- 24576767
TI  - Development of a sensitive LC/MS/MS method for vitamin D metabolites: 1,25
      Dihydroxyvitamin D2&3 measurement using a novel derivatization agent.
AB  - Active vitamin D metabolites 1,25-dihydroxyvitamin D2 [1,25-(OH)2-D2; derived
      from ergocalciferol] and D3 [1,25-(OH)2-D3; derived from cholecalciferol] are
      found in low levels in the circulation and require a very sensitive method for
      measurement. Radioimmunoassay (RIA) has been the method of choice, but it lacks
      the specificity needed to distinguish between 1,25-(OH)2-D2 and -D3, whereas
      liquid chromatography-tandem mass spectrometry (LC/MS/MS) methods have the
      advantage of high specificity and sensitivity. Here, we compare a new derivative
      for ionizing 1,25-(OH)2-D to enhance the signal and provide the most sensitive
      assay for measuring vitamin D. We used the Amplifex diene method of derivatizing
      prior to LC/MS/MS and compared it to the standard RIA method and the 4-phenyl
      1,2,4-triazole-3,5-dione (PTAD) method of derivatizing prior to LC/MS/MS. In the
      evaluation of 20 human serum samples, all methods correlated strongly across the
      upper levels of the standard 1,25-(OH)2-D2 and -D3 ranges (Amplifex and RIA,
      pc=0.97; Amplifex and PTAD, pc=0.96) but less strongly on the lower levels of the
      standard range (Amplifex and RIA, pc=0.81; Amplifex and PTAD, pc=0.65) suggesting
      differences in the sensitivities between the assays. The Amplifex method was
      determined to be more sensitive than the PTAD method, as peak areas were
      significantly higher for the Amplifex method and provided for a 10 fold higher
      signal-to-noise ratio than PTAD. Therefore, the Amplifex LC/MS/MS method is the
      most sensitive and specific method available for measuring 1,25-(OH)2-D2 and -D3
      while using the smallest sample volume. 

PMID- 24576768
TI  - Utilization of a precolumn with size exclusion and reversed-phase modes for size
      exclusion chromatographic analysis of polysorbate-containing protein aggregates.
AB  - Size-exclusion chromatography (SEC) is a useful method for quantification of
      protein aggregates because of its high throughput capacity and highly
      quantitative performance. One of the problems in this method concerns
      polysorbates, which are well-known additives for protein-containing products to
      prevent protein aggregation, but frequently interfere with the photometric
      detection of protein aggregates. We developed a new SEC method that can separate
      polysorbates from protein sample solutions in an on-line mode with a precolumn
      with size exclusion and reversed-phase mixed modes. The precolumn can effectively
      trap polysorbates in aqueous mobile phase, and the trapped polysorbates are
      easily eluted with acetonitrile-containing aqueous mobile phase to clean the
      precolumn. Small parts of protein aggregates may be also trapped on the precolumn
      depending on temperature and proteins. Setting appropriate column temperature can
      minimize such inconvenient trapping of aggregates. 

PMID- 24576770
TI  - Influence of fresh date palm co-products on the ripening of a paprika added dry
      cured sausage model system.
AB  - Date palm co-products are a source of bioactive compounds that could be used as a
      new ingredient for the meat industry. An intermediate food product (IFP) from
      date palm co-products (5%) was incorporated into a paprika added dry-cured
      sausage (PADS) model system and was analysed for physicochemical parameters,
      lipid oxidation and sensory attributes during ripening. Addition of 5% IFP
      yielded a product with physicochemical properties similar to the traditional one.
      Instrumental colour differences were found, but were not detected visually by
      panellists, who also evaluated positively the sensory properties of the PADS with
      IFP. Therefore, the IFP from date palm co-products could be used as a natural
      ingredient in the formulation of PADS. 

PMID- 24576769
TI  - A sensitive and fast LC-MS/MS method for determination of beta-receptor agonist
      JP-49b: application to a pharmacokinetic study in rats.
AB  - Ocular administration of the beta (beta)-adrenergic receptor agonist JP-49b
      prevents retinopathy-like damage in a preclinical rat model of diabetes.
      Importantly, JP-49b did not induce characteristic beta-adrenergic agonist-related
      side effects (e.g., left ventricular damage), which led to the hypothesis that JP
      49b systemic exposure was minimal following ocular administration. To test this
      hypothesis, a sensitive liquid chromatography tandem mass spectrometry (LC-MS/MS)
      method was developed to study the preclinical pharmacokinetics of JP-49b in rats.
      Animals received either a single periocular or intravenous injection of JP-49b
      (10mg/kg) and plasma and tissue samples were obtained. JP-49b and fenoterol
      hydrobromide (internal standard, IS) were isolated by liquid-liquid extraction
      and extracts were analyzed by reversed-phase liquid chromatography on a C18
      column using a gradient elution (acetic acid in water and methanol). A triple
      quadrupole mass spectrometer operating in the positive electrospray ionization
      mode with multiple reaction monitoring was used to detect JP-49b and IS
      transitions of m/z 346.4->195.1 and 304.1->134.9. The method was validated for
      selectivity, linearity, accuracy, and precision in rat vitreous humor, tissue
      homogenates, and plasma. Following intravenous administration, JP-49b was found
      to have a rapid clearance (36+/-5.8L/h/kg), high volume of distribution (244+/
      51.5L/kg) and a terminal half-life of 4.8+/-1.6h. JP-49b was rapidly absorbed and
      extensively distributed into ocular tissue following topical administration.
      However, JP-49b was undetectable in heart tissue 24h after ocular administration.
      High local drug concentrations coupled with minimal systemic exposure following
      ocular administration supports further testing of JP-49b as a localized therapy
      for diabetic retinopathy. 

PMID- 24576771
TI  - Influence of infrared final cooking on polycyclic aromatic hydrocarbon formation
      in ohmically pre-cooked beef meatballs.
AB  - Effects of infrared cooking on polycyclic aromatic hydrocarbon (PAH) formation in
      ohmically pre-cooked beef meatballs were investigated. Samples were pre-cooked in
      a specially designed-continuous type ohmic cooking at a voltage gradient of
      15.26V/cm for 92s. Infrared cooking was applied as a final cooking method at
      different combinations of heat fluxes (3.706, 5.678, 8.475kW/m(2)), application
      distances (10.5, 13.5, 16.5cm) and application durations (4, 8, 12min). PAHs were
      analyzed by using high performance liquid chromatography (HPLC) equipped with a
      fluorescence detector. The total PAH levels were detected to be between 4.47 and
      64MUg/kg. Benzo[a] pyrene (B[a]P) and PAH4 (sum of B[a]P, chrysene (Chr),
      benzo[a]anthracene (B[a]A) and benzo[b]fluoranthene (B[b]F)) levels detected in
      meatballs were below the EC limits. Ohmic pre-cooking followed by infrared
      cooking may be regarded as a safe cooking procedure of meatballs from a PAH
      contamination point of view. 

PMID- 24576772
TI  - Association of blood glucose, blood lactate, serum cortisol levels, muscle
      metabolites, muscle fiber type composition, and pork quality traits.
AB  - The objective of this study was to investigate the relationship of blood glucose
      levels with blood lactate, serum cortisol levels, postmortem muscle glycogen and
      lactate content, muscle fiber type composition, and pork quality traits. Compared
      to pigs with lower blood glucose levels, pigs with higher blood glucose levels
      showed higher blood lactate and serum cortisol levels at exsanguination, and they
      had lower residual glycogen and higher lactate content in the muscle at 45min
      postmortem. In addition, pigs with higher blood glucose levels had higher type
      IIB and lower type I area composition and finally exhibited lower muscle pH,
      paler color, and excessive loss of fluid on surface. These results imply that
      measuring blood glucose levels at exsanguination can be useful to indicate early
      glycolytic rates during postmortem and thus may be of value in the identification
      of pork with undesirable quality traits. 

PMID- 24576774
TI  - High-sensitivity troponin level pre-catheterization predicts adverse
      cardiovascular outcomes after primary angioplasty for ST-elevation myocardial
      infarction.
AB  - BACKGROUND: Cardiac troponins are the preferred biomarkers for diagnosing
      myocardial infarction (MI). High-sensitivity troponin T (hs-TnT) assays have
      increased sensitivity and enable more rapid diagnosis of infarction. We assessed
      the prognostic utility of admission hs-TnT to detect outcomes after primary
      angioplasty for ST-elevation/new left bundle branch block myocardial infarction
      (STEMI). METHODS: Patients admitted to Auckland City Hospital for acute coronary
      catheterization with a diagnosis of STEMI between October 2010 and September 2011
      were identified, and included if hs-TnT levels were measured at admission.
      Clinical characteristics and major adverse cardiovascular events (MACE: death,
      myocardial infarction and revascularization) at 30 days and 1 year were collected
      from national statistics and electronic medical records. RESULTS: Median
      admission hs-TnT level in the 173 STEMI patients studied was 59 ng/L
      (interquartile range (IQR) 19-310). Incidences of MACE at 30 days and 1 year were
      10% (n=17) and 18% (n=31), respectively. C-statistics and 95% confidence interval
      (CI) (95% CI) for hs-TnT on admission at detecting MACE at 30 days and 1 year
      were 0.800 (0.696-0.904) and 0.750 (0.655-0.845) respectively, with the optimal
      cut-point of 225 ng/L giving sensitivities/specificities of 76.5%/75.6% and
      64.5%/78.2% respectively. Admission log(hs-TnT) independently predicted both MACE
      at 30 days with hazards ratio 5.16, 95% CI (2.25-11.9) and 1 year with hazards
      ratio 2.88, 95% CI (1.79-4.63), as did age and cardiogenic shock. Age, Maori or
      Pacific ethnicity and chronic respiratory disease were independent predictors of
      hs-TnT>225 ng/L. CONCLUSION: Admission hs-TnT measured in primary angioplasty is
      strongly prognostic of MACE at 30 days and 1 year, even following adjustment for
      potential confounding variables.

PMID- 24576773
TI  - [Lipoprotein(a) is associated to atherosclerosis in primary
      hypercholesterolemia].
AB  - INTRODUCTION: Several studies have suggested that Lp(a) could be a risk factor
      mainly in hypercholesterolemic patients. METHODS: A total of 909 individuals were
      selected for this study. 307 were diagnosed of familiar hypercholesterolemia with
      a pathogenic mutation in LDLR or APOB genes (FH+), 291 of familiar combined
      hyperlipidemia (FCH) and 311 of familial hypercholesterolemia without a
      pathogenic mutation in LDLR nor APOB genes (FH-). Main risk factor were studied,
      included statin treatment. Plasma lipids, Lp(a), HbA1c and C-reactive protein.
      Intima-media thickness (IMT) of common and bulb carotid in both sides were
      measured in all subjects. RESULTS: Lp(a) values (median, interquartile range)
      were 21.9mg/dL (9.24-50.5) in FH+, 22.4mg/dL (6.56-51.6) in FCH and 32.7 (14.6
      71.5) in FH- (P<.001). Regression analysis including age, gender, HDL
      cholesterol, LDL cholesterol corrected for Lp(a), Lp(a), C-reactive protein,
      packs of cigarettes/day per year, systolic blood pressure and glucose as
      independent variables, demonstrate that Lp(a) was associated with carotid IMT in
      FH- subjects. Cardiovascular disease was more frequent in subjects with Lp(a)
      >50mg/dL (17.9%) than in subjects with Lp(a) <15mg/dL (9.6%), and between 15
      50mg/dL (10.1%), and it was concentrated mostly in FH-group (6.7, 11.3, and 23.4%
      for the groups of Lp(a) <15mg/dL 15-50mg/dL, and >50mg/dL, respectively).
      CONCLUSIONS: Our results indicate that Lp(a) is associated with atherosclerosis
      burden especially in subjects with FH- and concentrations of Lp(a)>50mg/dL.

PMID- 24576775
TI  - Treatment for early-stage lung cancer: what next?

PMID- 24576777
TI  - Expression and prognostic significance of p21-activated kinase 6 in
      hepatocellular carcinoma.
AB  - BACKGROUND: p21-activated protein kinase (PAK) 6 is a serine-threonine kinase
      belonging to the PAK family. Previous studies have indicated that abnormal
      expressions of PAK1, PAK2, and PAK5 played critical roles in hepatocellular
      carcinoma (HCC). Recent studies suggested that deregulation of PAK6 expression
      played an important role in oncogenesis. To explore the potential roles of PAK6
      in HCC, expression of PAK6 was detected in human HCC specimens. METHODS:
      Immunohistochemistry and Western blot analysis were performed for PAK6 in 121 HCC
      samples. The data were correlated with clinicopathologic features. The univariate
      and multivariate survival analyses were also performed to determine their
      clinical prognostic significance. RESULTS: PAK6 was overexpressed in HCC as
      compared with the adjacent noncancerous liver tissues. High expression of PAK6
      was associated with Edmondson-Steiner grade (P = 0.006) and number of tumor
      nodules (P < 0.001), and PAK6 was positively correlated with proliferation marker
      Ki-67 (P < 0.01). Univariate analysis suggested that PAK6 expression was
      associated with poor prognosis (P < 0.001). Multivariate analysis indicated that
      PAK6 and Ki-67 protein expressions were independent prognostic markers for HCC (P
      = 0.0245 and 0.0331, respectively). CONCLUSIONS: Our results suggest that PAK6
      overexpression is involved in the pathogenesis of HCC; it may be an independent
      poor prognostic factor for HCC.

PMID- 24576778
TI  - The influence of socioeconomic factors on gender disparities in lower extremity
      bypass.
AB  - BACKGROUND: Some contend that gender differences in outcomes after lower
      extremity bypass (LEB) for peripheral arterial disease (PAD) relate to
      socioeconomic factors (SEFs). Here, we evaluate these disparities with attention
      to clinically relevant yet understudied SEF. METHODS: A retrospective cohort
      study of patients aged >50 y with PAD undergoing LEB was performed using data
      from Pennsylvania Health care and Cost Containment Council (2003-2011).
      Multivariable logistic regression modeling was performed to evaluate the
      association between gender and outcomes with adjustment for potential confounders
      including SEF such as income, insurance provider, distance to hospital, and race.
      Generalized estimating equations were used to adjust for hospital clustering.
      Independent models were developed to examine death or serious morbidity (DSM) and
      failure-to-rescue (FTR). RESULTS: Of 4202 patients identified, 1510 (36%) were
      women. SEF differed by gender. DSM was more frequent in women (15.6% versus
      12.2%; P = 0.002). There was no association between gender and FTR in univariate
      analysis (P = 0.49). SEFs were associated with DSM and FTR. After adjustment for
      potential confounders including SEF, women remained more likely to experience DSM
      (odds ratio = 1.28; P = 0.01). There remained no significant association between
      gender and FTR on independent modeling (odds ratio = 0.49; P = 0.11).
      CONCLUSIONS: Women undergoing LEB in the state of Pennsylvania are at increased
      risk of poor outcomes, which is not completely explained by SEF. Quality of
      postoperative care does not appear to be different between gender as there was no
      difference in FTR. To improve these outcomes, efforts should be made to increase
      awareness of PAD and promote screening among high-risk women to ensure timely
      diagnosis and referral.

PMID- 24576776
TI  - Preoperative chemotherapy for non-small-cell lung cancer: a systematic review and
      meta-analysis of individual participant data.
AB  - BACKGROUND: Individual participant data meta-analyses of postoperative
      chemotherapy have shown improved survival for patients with non-small-cell lung
      cancer (NSCLC). We aimed to do a systematic review and individual participant
      data meta-analysis to establish the effect of preoperative chemotherapy for
      patients with resectable NSCLC. METHODS: We systematically searched for trials
      that started after January, 1965. Updated individual participant data were
      centrally collected, checked, and analysed. Results from individual randomised
      controlled trials (both published and unpublished) were combined using a two
      stage fixed-effect model. Our primary outcome, overall survival, was defined as
      the time from randomisation until death (any cause), with living patients
      censored on the date of last follow-up. Secondary outcomes were recurrence-free
      survival, time to locoregional and distant recurrence, cause-specific survival,
      complete and overall resection rates, and postoperative mortality. Prespecified
      analyses explored any variation in effect by trial and patient characteristics.
      All analyses were by intention to treat. FINDINGS: Analyses of 15 randomised
      controlled trials (2385 patients) showed a significant benefit of preoperative
      chemotherapy on survival (hazard ratio [HR] 0.87, 95% CI 0.78-0.96, p=0.007), a
      13% reduction in the relative risk of death (no evidence of a difference between
      trials; p=0.18, I(2)=25%). This finding represents an absolute survival
      improvement of 5% at 5 years, from 40% to 45%. There was no clear evidence of a
      difference in the effect on survival by chemotherapy regimen or scheduling,
      number of drugs, platinum agent used, or whether postoperative radiotherapy was
      given. There was no clear evidence that particular types of patient defined by
      age, sex, performance status, histology, or clinical stage benefited more or less
      from preoperative chemotherapy. Recurrence-free survival (HR 0.85, 95% CI 0.76
      0.94, p=0.002) and time to distant recurrence (0.69, 0.58-0.82, p<0.0001) results
      were both significantly in favour of preoperative chemotherapy although most
      patients included were stage IB-IIIA. Results for time to locoregional recurrence
      (0.88, 0.73-1.07, p=0.20), although in favour of preoperative chemotherapy, were
      not statistically significant. INTERPRETATION: Findings, which are based on 92%
      of all patients who were randomised, and mainly stage IB-IIIA, show preoperative
      chemotherapy significantly improves overall survival, time to distant recurrence,
      and recurrence-free survival in resectable NSCLC. The findings suggest this is a
      valid treatment option for most of these patients. Toxic effects could not be
      assessed. FUNDING: Medical Research Council UK.

PMID- 24576781
TI  - The importance of longitudinal cohort studies in understanding risk and
      protective factors for dementia.

PMID- 24576779
TI  - Docosahexaenoic acid, G protein-coupled receptors, and melanoma: is G protein
      coupled receptor 40 a potential therapeutic target?
AB  - BACKGROUND: To determine the effect of docosahexaenoic acid (DHA) on the growth
      of human melanoma in vitro and in vivo and to better understand the potential
      role of the G protein-coupled receptors (GPRs) in mediating this effect.
      MATERIALS AND METHODS: For in vitro studies, human melanoma and control
      fibroblast cells were treated with DHA and TAK-875 (selective GPR40 agonist) and
      a cell viability assay was performed to determine cell counts. A murine
      subcutaneous xenograft model of human melanoma was used to test the effect of
      dietary treatment with an omega-3 fatty acid (FA) rich diet compared with an
      omega-6 FA rich diet on the growth of human melanoma in vivo. A similar animal
      model was used to test the effect of oral TAK-875 on the growth of established
      melanoma tumors in vivo. RESULTS: DHA has an inhibitory effect on the growth of
      human melanoma both in vitro and in vivo. Tumors from animals on the omega-3 FA
      rich diet were 69% smaller in weight (P = 0.005) and 76% smaller in volume
      compared with tumors from animals on the omega-6 FA rich diet. TAK-875 has an
      inhibitory effect on the growth of human melanoma both in vitro and in vivo.
      Tumors from animals treated with TAK-875 were 46% smaller in weight (P = 0.07),
      62% smaller in volume (P = 0.03), and grew 77% slower (P = 0.04) compared with
      the placebo group. CONCLUSIONS: DHA and TAK-875 have a profound and selective
      inhibitory effect on the growth of human melanoma both in vitro and in vivo.

PMID- 24576780
TI  - Pulsatilla saponin A, an active molecule from Pulsatilla chinensis, induces
      cancer cell death and inhibits tumor growth in mouse xenograft models.
AB  - BACKGROUND: Many natural compounds possess antitumor growth activities.
      Pulsatilla chinensis is an herb used in traditional Chinese medicine to treat
      infectious diseases. More recently, extracts from P chinensis have been shown to
      contain antitumor activities. MATERIALS AND METHODS: In this study, we isolated
      Pulsatilla saponin A as an active compound from P chinensis extracts and tested
      its anticancer activity in vitro and in vivo. RESULTS: In cell culture,
      Pulsatilla saponin A significantly inhibited the growth of human hepatocellular
      carcinoma SMCC-7721 cells and pancreatic BXPC3 and SW1990 cancer cells. Similar
      inhibitory activities were observed when the compound was tested in mouse
      xenograft tumor models using human hepatocellular carcinoma Bel-7402 and
      pancreatic cancer SW1990 cells. In Comet assay and flow cytometric analysis of
      cell cycle distribution and annexin V expression, DNA damage, G2 arrest, and
      apoptosis were identified in Pulsatilla saponin A-treated cancer cells. Based on
      the results of Western blotting, p53 and cyclin B protein levels were higher,
      whereas Bcl-2 protein levels were lower in Pulsatilla saponin A-treated cancer
      cells than in vehicle-treated cells. CONCLUSIONS: Pulsatilla saponin A may exert
      its antitumor effect by inducing DNA damage and causing G2 arrest and apoptosis
      in cancer cells. Pulsatilla saponin A and its derivatives may be developed as a
      new class of anticancer agents.

PMID- 24576783
TI  - Increasing human leg motor cortex excitability by transcranial high frequency
      random noise stimulation.
AB  - PURPOSE: Transcranial random noise stimulation (tRNS) can increase the
      excitability of hand area of the primary motor cortex (M1). The aim of this study
      was to compare the efficacy of tRNS and transcranial direct current stimulation
      (tDCS) on the leg motor cortex. METHOD: Ten healthy subjects received anodal,
      cathodal tDCS, tRNS and sham stimulation for 10 min using 2 mA intensity during
      separate experimental sessions. Single pulse transcranial magnetic stimulation
      (TMS) induced motor evoked potential (MEP) measurements were used to assess motor
      cortical excitability changes after the stimulation. RESULTS: Similar to the hand
      area, we found that both tRNS and anodal tDCS induced an increase of the
      amplitude of the MEPs. Anodal tDCS induced a constant gradual increase of
      corticospinal excitability until 60 min post-stimulation, whereas the effect of
      tRNS was immediate with a duration of 40 min following stimulation. The cathodal
      tDCS induced decrease in MEP amplitude did not reach statistical significance.
      CONCLUSION: Our results suggest that although the leg area has a deeper position
      in the cortex compared to the hand area, it can be reached by weak transcranial
      currents. Both anodal tDCS and tRNS had comparable effect on cortical
      excitability.

PMID- 24576782
TI  - Occurrence of brominated flame retardants (BFRs), organochlorine pesticides
      (OCPs), and polychlorinated biphenyls (PCBs) in agricultural soils in a BFR
      manufacturing region of North China.
AB  - We investigated the occurrence of brominated flame retardants (BFRs),
      organochlorine pesticides (OCPs), and polychlorinated biphenyls (PCBs) in the
      surface soils from the largest BFR-manufacturing and vegetable farming center
      (Shouguang) of North China. The total concentrations of BFRs ranged from 39.9 to
      8,145 ng/g dry weight with a mean of 1,947 ng/g. The BFRs were dominated by
      decabromodiphenylethane (deca-BDEs) and tetrabromobisphenol A (TBBPA), with means
      of 1127 and 672 ng/g, respectively, followed by decabromodiphenyl ethane (DBDPE)
      (111 ng/g) and hexabromocyclododecanes (HBCD) (37.5 ng/g). This profile was
      generally consistent with the BFR production and use in China, except for TBBPA.
      Although the lower brominated BDEs (tri- through hepta-BDEs) in the soil may
      originate from technical deca-BDE mixtures as trace impurities and/or from the
      degradation of deca-BDEs, deca-BDE was shown to be persistent in the soil. The
      concentrations of OCPs (44 ng/g) were significantly lower than those of BFRs and
      displayed a spatial distribution opposite to that of BFRs, which was concentrated
      in the industrial zone. PCBs (with the lowest levels) showed a relatively uniform
      spatial distribution because of regional diffusive sources. The mass inventories
      for the entire land soil (20-cm) were estimated to be 1042, 26, and 3.7 t for
      BFRs, OCPs, and PCBs, respectively.

PMID- 24576784
TI  - [John Singer Sargent, Spain and the horrors of chemical warfare].

PMID- 24576786
TI  - Interaction between substrates suggests a relationship between organophosphorus
      sensitive phenylvalerate- and acetylcholine-hydrolyzing activities in chicken
      brain.
AB  - Organophosphorus compounds (OPs) induce neurotoxic disorders through interactions
      with well-known target esterases, such as acetylcholinesterase and neuropathy
      target esterase (NTE). However, OPs interact with other esterases of unknown
      biological function. In soluble chicken brain fractions, three components of
      enzymatic phenylvalerate esterase activity (PVase) called Ealpha, Ebeta and
      Egamma, have been kinetically discriminated. These components are studied in this
      work for the relationship with acetylcholine-hydrolyzing activity. When Ealpha
      PVase activity (resistant PVase activity to 1500 MUM PMSF for 30 min) was tested
      with different acetylthiocholine concentrations, inhibition was observed. The
      best-fitting model to the data was the non-competitive inhibition model (Km=0.12,
      0.22 mM, Ki=6.6, 7.6 mM). Resistant acetylthiocholine-hydrolyzing activity to
      1500 MUM PMSF was inhibited by phenylvalerate showing competitive inhibition
      (Km=0.09, 0.11 mM; Ki=1.7, 2.2 mM). Ebeta PVase activity (resistant PVase
      activity to 25 MUM mipafox for 30 min) was not affected by the presence of
      acetylthiocholine, while resistant acetylthiocholine-hydrolyzing activity to 25
      MUM mipafox showed competitive inhibition in the presence of phenylvalerate
      (Km=0.05, 0.06 mM; Ki=0.44, 0.58 mM). The interactions observed between the
      substrates of AChE and PVase suggest that part of PVase activity might be a
      protein with acetylthiocholine-hydrolyzing activity.

PMID- 24576787
TI  - Uptake of different crystal structures of TiO2 nanoparticles by Caco-2 intestinal
      cells.
AB  - The gastrointestinal uptake of different crystal structures of TiO2 was
      investigated using Caco-2 intestinal cells. Caco-2 monolayers exhibited time
      dependent, saturable uptake of Ti from TiO2 exposures of 1 mgl(-1) over 24h,
      which was influenced by crystal type. Initial uptake rates were 5.3, 3.73, 3.58
      and 4.48 nmol mg(-1)protein h(-1) for bulk, P25, anatase and rutile forms
      respectively. All exposures caused elevations of Ti in the cells relative to the
      control (ANOVA P<0.05). Electron micrographs of the Caco-2 monolayer showed the
      presence of particles inside the cells, and energy dispersive spectroscopy (EDS)
      confirmed the composition as TiO2. Incubating the cells with 120 IU nystatin
      (putative endocytosis inhibitor) or 100 MUmol l(-1) vanadate (ATPase inhibitor)
      caused large increases in Ti accumulation for all crystal types relative to
      controls (ANOVA P<0.05), except for the rutile form with vanadate. Incubating the
      cells with 90 MUmol l(-1) genistein (tyrosine kinase inhibitor) or 27 MUmol l(-1)
      chloropromazine (clathrin-mediated endocytosis inhibitor) caused a large decrease
      in Ti accumulation relative to the controls (ANOVA P<0.05). Cell viability
      measures were generally good (low LDH leak, normal cell morphology), but there
      were some changes in the electrolyte composition (K(+), Na(+), Ca(2+), Mg(2+)) of
      exposed cells relative to controls. A rise in total Ca(2+) concentration in the
      cells was observed for all TiO2 crystal type exposures. Overall, the data shows
      that Ti accumulation for TiO2 NP exposure in Caco-2 cells is crystal structure
      dependent, and that the mechanism(s) involves endocytosis of intact particles.

PMID- 24576789
TI  - Pigmentary lines of the newborn: a case report and review of the literature.
AB  - Various diseases of pigmentation in the newborn are known, such as congenital or
      acquired linear hyperpigmentation. Pigmentary lines of the newborn are counted
      among the transient benign cutaneous lesions in the newborn and appear to be
      rather rare. This paper reports on a newborn with pigmentary lines in the creases
      of the abdomen. The 5-month-old boy is the first case observed so far in the
      University Hospital of Basel in Switzerland. He was born at term and healthy,
      without any congenital abnormalities. The horizontally arranged linear
      hyperpigmentation appeared shortly after birth and faded spontaneously after 5
      months. Pigmentary lines of the newborn are rare and the non-hormonal cause may
      be flexion in utero or other mechanically induced stimulation. So far, only eight
      similar cases have been reported, which are listed in a table.

PMID- 24576785
TI  - Is organic farming safer to farmers' health? A comparison between organic and
      traditional farming.
AB  - Exposure to pesticides is a major public health concern, because of the
      widespread distribution of these compounds and their possible long term effects.
      Recently, organic farming has been introduced as a consumer and environmental
      friendly agricultural system, although little is known about the effects on
      workers' health. The aim of this work was to evaluate genetic damage and
      immunological alterations in workers of both traditional and organic farming.
      Eighty-five farmers exposed to several pesticides, thirty-six organic farmers and
      sixty-one controls took part in the study. Biomarkers of exposure (pyrethroids,
      organophosphates, carbamates, and thioethers in urine and butyrylcholinesterase
      activity in plasma), early effect (micronuclei in lymphocytes and reticulocytes,
      T-cell receptor mutation assay, chromosomal aberrations, comet assay and
      lymphocytes subpopulations) and susceptibility (genetic polymorphisms related to
      metabolism - EPHX1, GSTM1, GSTT1 and GSTP1 - and DNA repair-XRCC1 and XRCC2) were
      evaluated. When compared to controls and organic farmers, pesticide farmers
      presented a significant increase of micronuclei in lymphocytes (frequency ratio,
      FR=2.80) and reticulocytes (FR=1.89), chromosomal aberrations (FR=2.19), DNA
      damage assessed by comet assay (mean ratio, MR=1.71), and a significant decrease
      in the proportion of B lymphocytes (MR=0.88). Results were not consistent for
      organic farmers when compared to controls, with a 48% increase of micronuclei in
      lumphocytes frequency (p=0.016) contrasted by the significant decreases of TCR-Mf
      (p=0.001) and %T (p=0.001). Our data confirm the increased presence of DNA damage
      in farmers exposed to pesticides, and show as exposure conditions may influence
      observed effects. These results must be interpreted with caution due to the small
      size of the sample and the unbalanced distribution of individuals in the three
      study groups. 

PMID- 24576788
TI  - The prevalence of diabetic cardiomyopathy: a population-based study in Olmsted
      County, Minnesota.
AB  - BACKGROUND: Diabetic cardiomyopathy defined as either systolic or diastolic
      dysfunction in otherwise healthy diabetic persons is not clearly understood. The
      prevalence and outcomes of this disease in a community-based population have not
      been defined. METHODS AND RESULTS: Cross-sectional survey of 2042 randomly
      selected residents of Olmsted County, Minnesota, aged 45 years or older between
      June 1997 and September 2000. All patients underwent Doppler echocardiographic
      assessment of systolic and diastolic function. Diabetic cardiomyopathy was
      defined in a person with diabetes and any systolic or at least moderate diastolic
      dysfunction without a history of coronary disease, hypertension, significant
      valvular disease, or congenital heart disease. The diagnosis of diabetic
      cardiomyopathy was made in 23 people, corresponding to a community population
      prevalence rate of 1.1%. Among diabetic patients, 16.9% met criteria for diabetic
      cardiomyopathy and 54.4% had diastolic dysfunction. Diabetes was associated with
      a 1.9-fold increase in risk of any left ventricular dysfunction, a 1.7-fold
      increase in risk of diastolic dysfunction, and a 2.2-fold increase in risk of
      systolic dysfunction. Among patients with diabetic cardiomyopathy, the cumulative
      probability of death was 18%, development of heart failure was 22%, and
      development of death or heart failure was 31% at 9 years. CONCLUSION: Diabetic
      cardiomyopathy is relatively common in the community with a prevalence of 1.1%.
      The morbidity and mortality of patients with diabetic cardiomyopathy is high.

PMID- 24576790
TI  - Obsessive-compulsive disorder.
AB  - Obsessive-compulsive disorder (OCD) is a common heterogeneous psychiatric
      disorder manifesting with obsessions and compulsions. Obsessions are intrusive,
      recurrent, and persistent unwanted thoughts. Compulsions are repetitive behaviors
      or mental acts that an individual feels driven to perform in response to the
      obsessions. The heterogeneity of OCD includes themes of obsessions, types of
      rituals, presence or absence of tics, etiology, genetics, and response to
      pharmacotherapy. Complications of OCD include interpersonal difficulties,
      unemployment, substance abuse, criminal justice issues, and physical injuries.
      Areas of the brain involved in the pathophysiology include the orbitofrontal
      cortex, anterior cingulate gyrus, and basal ganglia. Overall, OCD may be due to a
      malfunction in the cortico-striato-thalamo-cortical circuit in the brain.
      Neurotransmitters implicated in OCD include serotonin, dopamine, and glutamate.
      Numerous drugs such as atypical antipsychotics and dopaminergic agents can cause
      or exacerbate OCD symptoms. The etiology includes genetics and neurological
      insults. Treatment of OCD includes psychotherapy, pharmacotherapy,
      electroconvulsive therapy, transcranial magnetic simulation, and in extreme cases
      surgery. Exposure and response prevention is the most effective form of
      psychotherapy. Selective serotonin reuptake inhibitors (SSRIs) are the preferred
      pharmacotherapy. Higher doses than listed in the package insert and a longer
      trial are often needed for SSRIs than compared to other psychiatric disorders.
      Alternatives to SSRIs include clomipramine and serotonin/norepinephrine reuptake
      inhibitors. Treatment of resistant cases includes augmentation with atypical
      antipsychotics, pindolol, buspirone, and glutamate-blocking agents. 

PMID- 24576791
TI  - Cost-effectiveness analysis of levonorgestrel-releasing intrauterine system (LNG
      IUS) 13.5 mg in contraception.
AB  - BACKGROUND: Levonorgestrel-releasing intrauterine system (LNG-IUS) 13.5 mg (total
      content) is a low-dose levonorgestrel intrauterine system for up to 3 years of
      use. This analysis evaluated the cost-effectiveness of LNG-IUS 13.5 mg in
      comparison with short-acting reversible contraceptive (SARC) methods in a cohort
      of young women in the United States from a third-party payer's perspective. STUDY
      DESIGN: A state transition model consisting of three mutually exclusive health
      states -- initial method, unintended pregnancy (UP) and subsequent method -- was
      developed. Cost-effectiveness of LNG-IUS 13.5 mg was assessed vs. SARC methods in
      a cohort of 1000 women aged 20-29 years. SARC methods comprise oral
      contraceptives (OC), ring, patch and injections, which are the methods commonly
      used by this cohort. Failure and discontinuation probabilities were based on
      published literature, contraceptive uptake was determined by the most recent data
      from the National Survey of Family Growth, and costs were taken from standard US
      databases. One-way sensitivity analysis was conducted around key inputs, while
      scenario analysis assessed a comparison between LNG-IUS 13.5 mg and the existing
      IUS, LNG-IUS 20 mcg/24 h. The key model output was cost per UP avoided. RESULTS:
      Compared to SARC methods, initiating contraception with LNG-IUS 13.5 mg resulted
      in fewer UP (64 UP vs. 276 UP) and lower total costs ($1,283,479 USD vs.
      $1,862,633 USD, a 31% saving) over the 3-year time horizon. Results were most
      sensitive to the probability of failure on OC, the probability of LNG-IUS 13.5 mg
      discontinuation and the cost of live births. Scenario analysis suggests that
      further cost savings may be generated with the initiation of LNG-IUS 20 mcg/24 h
      in place of SARC methods. CONCLUSIONS: From a third-party payer perspective, LNG
      IUS 13.5 mg is a more cost-effective contraceptive option than SARC. Therefore,
      women switching from current SARC use to LNG-IUS 13.5 mg are likely to generate
      cost savings to third-party health care payers, driven principally by decreased
      UP-related expenditures and long-term savings in contraceptive costs.

PMID- 24576792
TI  - Provider acceptability of Sayana(r) Press: results from community health workers
      and clinic-based providers in Uganda and Senegal.
AB  - BACKGROUND: Sayana(r) Press (SP), a subcutaneous formulation of depot
      medroxyprogesterone acetate (DMPA) in UnijectTM, has potential to be a valuable
      innovation in family planning (FP) because it may overcome logistic and safety
      challenges in delivering intramuscular DMPA (DMPA IM). However, SP's
      acceptability is unknown. We measured acceptability of SP among clinic-based
      providers (Senegal only) and community health workers. STUDY DESIGN: This open
      label observational study was conducted in clinics in three districts in Senegal
      and community-based services in two districts in Uganda. Providers administered
      SP to clients seeking reinjection of DMPA IM. We conducted in-depth interviews
      with 86 providers (52 in Senegal, 34 in Uganda) to assess their experiences
      providing SP to clients. RESULTS: Almost all providers (84/86; 98%) preferred SP
      over DMPA IM. The main reason Uganda providers preferred SP was the prefilled/all
      in-one design made preparation and administration easier and faster. Some
      providers thought the SP all-in-one feature may decrease stock outs (DMPA IM
      requires syringe and vial). Providers also felt clients preferred the shorter SP
      needle because it is less intimidating and less painful. Similarly, the main
      reasons Senegal providers preferred SP were its characteristics (prefilled/all-in
      one) and client preference (especially less pain). They also saw a potential to
      increase access to FP, especially through community-based distribution. Providers
      from both countries reported SP introduction would be enhanced through client
      counseling and community engagement. Providers also said SP must be accessible,
      affordable and in stock. CONCLUSION: Almost all providers preferred SP over DMPA
      IM. Provider recommendations should be considered during SP introduction
      planning. IMPLICATIONS: We found that SP was acceptable to both clinic-based FP
      providers and community health workers. Providers' positive attitudes towards SP
      may facilitate introduction and uptake of this method.

PMID- 24576793
TI  - Cardiovascular and general safety of a 24-day regimen of drospirenone-containing
      combined oral contraceptives: final results from the International Active
      Surveillance Study of Women Taking Oral Contraceptives.
AB  - OBJECTIVES: The "International Active Surveillance Study of Women Taking Oral
      Contraceptives" investigated the risks of short- and long-term use of an extended
      24-day regimen of drospirenone and ethinylestradiol (DRSP24d) compared to
      established oral contraceptives (OCs) in a routine clinical setting. STUDY
      DESIGN: Prospective, controlled, noninterventional cohort study conducted in the
      United States and six European countries with three main cohorts: new users of
      DRSP24d, DRSP21d (21-day regimens of DRSP-containing OCs), and non-DRSP (OCs
      without DRSP). All self-reported clinical outcomes of interest (OoI) were
      validated via attending physicians and relevant source documents. Main OoI were
      serious clinical outcomes, in particular venous thromboembolism (VTE).
      Comprehensive follow-up procedures were implemented. Statistical analyses were
      based on Cox regression models. Primary statistical variable was the VTE hazard
      ratio (HR) for DRSP24d vs. non-DRSP. RESULTS: A total of 2285 study centers
      enrolled 85,109 women. Study participants were followed for 2 to 6 years, which
      generated 206,296 woman-years (WY) of observation. A low loss to follow-up of
      3.3% was achieved. DRSP24d, DRSP21d, non-DRSP and levonorgestrel-containing OCs
      (LNG) showed similar incidence rates of venous and arterial thromboembolism,
      fatal outcomes, cancer, severe depression and other serious adverse events. VTE
      incidence rates for DRSP24d, DRSP21d, non-DRSP and LNG were 7.2, 9.4, 9.6 and 9.8
      VTE/10,000 WY, respectively. Adjusted HRs for DRSP24d vs. non-DRSP and DRSP24d
      vs. LNG were 0.8 [95% confidence interval (CI), 0.5-1.3] and 0.8 (95% CI, 0.4
      1.5). CONCLUSION: DRSP24d, DRSP21d, non-DRSP and LNG use was associated with
      similar risks of serious adverse events, and particularly VTE, during routine
      clinical use. IMPLICATION STATEMENT: The 24-day regimen of drospirenone
      containing combined OCs is associated with similar risks of venous and arterial
      thromboembolism, fatal outcomes, cancer, severe depression and other serious
      adverse events compared to 21-day regimens of drospirenone-containing combined
      OCs, OCs without drospirenone and LNGs.

PMID- 24576794
TI  - Efficacy and safety of an ascending-dose, extended-regimen levonorgestrel/ethinyl
      estradiol combined oral contraceptive.
AB  - OBJECTIVE: To evaluate the efficacy and safety of an ascending-dose, extended
      regimen (ADER) combined oral contraceptive consisting of levonorgestrel (LNG) 150
      mcg/ethinyl estradiol (EE) 20 mcg for 42 days, LNG 150 mcg/EE 25 mcg for 21 days,
      LNG 150 mcg/EE 30 mcg for 21 days and EE 10 mcg for 7 days. STUDY DESIGN: This
      was a multicenter, open-label, phase 3, single-arm study. Sexually active women
      aged 18-40 years were enrolled and received ADER for up to 1 year (4 consecutive
      91-day cycles). Participants kept diaries to record adherence, bleeding/spotting
      and other contraceptive use. Efficacy was measured using the Pearl Index and the
      life-table method; safety and tolerability were assessed through reported adverse
      events (AEs). RESULTS: A total of 3701 women were enrolled and 2144 completed the
      study. The Pearl Index was 3.19 [95% confidence interval (CI), 2.49-4.03], based
      on 70 pregnancies that occurred after ADER initiation and <= 7 days after the
      last LNG/EE or EE-only pill in women aged 18-35 years, excluding cycles in which
      another contraceptive method was used. Life-table pregnancy rate was 2.82% (95%
      CI, 2.23%-3.57%) for all users aged 18-35 years. Unscheduled bleeding/spotting
      decreased with increasing EE doses within each cycle and decreased after cycle 1.
      No unexpected AEs or changes in laboratory parameters were reported. CONCLUSION:
      This study demonstrated that ADER effectively prevented pregnancy with a
      favorable safety and tolerability profile.

PMID- 24576795
TI  - Contraception after cancer treatment: describing methods, counseling, and
      unintended pregnancy risk.
AB  - OBJECTIVE: The objective was to describe contraceptive methods utilized by young
      female cancer survivors and determine whether pretreatment fertility counseling
      decreases unintended pregnancy risk. METHODS: One thousand and forty-one
      nongynecologic cancer survivors between 18 and 40 years of age responded to a
      survey of reproductive health, contraceptive methods utilized and history of
      fertility counseling before cancer treatment. Subjects who had resumed menstrual
      bleeding following treatment and had not undergone surgical sterilization were
      defined at risk of unintended pregnancy if they reported unprotected vaginal
      intercourse in the prior month but did not desire conception. Statistical methods
      utilized were Student's t test and chi(2). RESULTS: Overall, 918 women (88%)
      received treatment with potential to affect fertility (chemotherapy, radiation or
      sterilizing surgery). Of 476 women younger than 40 years old who still had
      menses, 58% did not want to conceive; of these 275 women, 21% reported
      unprotected intercourse in the prior month and were defined at risk of unintended
      pregnancy. This compares to the 7.3% risk of unintended pregnancy reported by the
      National Center for Health Statistics. Increasing age was associated with greater
      risk of unintended pregnancy (odds ratio 1.07, p=.006). The following
      contraceptive methods were reported: barrier (25.5%), hormonal (24.5%), tubal
      ligation (21.3%) vasectomy (17.5%), intrauterine device (7.2%) and other (4.0%).
      Sixty-seven percent of women received pretreatment fertility counseling.
      Counseling prior to treatment did not decrease risk of unintended pregnancy
      (p=.93). CONCLUSIONS: Sexually active cancer survivors are at threefold increased
      risk of unintended pregnancy compared to the US population. Contraceptive
      counseling in this high-risk population is recommended posttreatment.
      IMPLICATIONS: Sexually active cancer survivors are at considerable risk of
      unintended pregnancy. Patient report of pretreatment counseling regarding
      fertility was not associated with a decline in risk of unintended pregnancy,
      highlighting the importance of clear recommendations regarding content and timing
      of counseling.

PMID- 24576796
TI  - The added value of 18-fluorodeoxyglucose-positron emission tomography in the
      diagnosis of the behavioral variant of frontotemporal dementia.
AB  - Characteristic frontotemporal abnormalities on structural or functional
      neuroimaging are mandatory for a diagnosis of probable behavioral variant of
      frontotemporal dementia (bvFTD) according to the new criteria. 18
      Fluorodeoxyglucose-positron emission tomography (18F-FDG-PET) imaging is commonly
      reserved for patients with suspected bvFTD without characteristic structural
      neuroimaging results. We studied the diagnostic value of 18F-FDG-PET in these
      patients. METHODS: The 18F-FDG-PET was performed in 52 patients with suspected
      bvFTD but lacking characteristic structural neuroimaging results. The clinical
      diagnosis of bvFTD in the presence of functional decline (bvFTD/fd+) after a
      follow-up period of 2 years was used as a golden standard. RESULTS: The
      sensitivity of 18F-FDG-PET for bvFTD/fd+ was 47% at a specificity of 92%. The
      differential diagnosis comprised alternative neurodegenerative and psychiatric
      disorders and a benign phenocopy of bvFTD. CONCLUSIONS: The 18F-FDG-PET is able
      to identify nearly half of the patients with bvFTD who remain undetected by
      magnetic resonance imaging. In our selected group, high specificity enables
      exclusion of psychiatric and other neurodegenerative disorders.

PMID- 24576797
TI  - Part I. Synthesis, biological evaluation and docking studies of new 2
      furylbenzimidazoles as antiangiogenic agents.
AB  - 2-(2-Furyl)-1H-benzimidazoles 3-11 were synthesized and tested for their in vitro
      VEGF inhibition in MCF-7 cancer cell line. Compound 5a was more potent than
      Tamoxifen, and compounds 3b, 5a, 5c, 6b, 7a and 10 showed promising potency.
      Furthermore, compounds (6b, 7a and 10) showed remarkable selective inhibition of
      COX-2 enzyme close to that of Celecoxcib. Additionally, docking studies were
      performed using AutoDock 4.2 into the VEGFR2 kinase. Significant correlation
      exists between the biological activity (IC50 and %VEGF inhibition) against MCF-7
      cell line and the molecular docking results (Ki and DeltaGb) with correlation
      coefficients (R(2)) of 0.5513 and 0.4623 respectively. Accordingly, most of the
      synthesized 2-(2-furyl)-1H-benzimidazoles showed strong antiangiogenic activity
      against VEGFR2 kinase.

PMID- 24576798
TI  - Cell biological roles of alphaB-crystallin.
AB  - alphaB-crystallin, also called HspB5, is a molecular chaperone able to interact
      with unfolding proteins. By interacting, it inhibits further unfolding, thereby
      preventing protein aggregation and allowing ATP-dependent chaperones to refold
      the proteins. alphaB-crystallin belongs to the family of small heat-shock
      proteins (sHsps), which in humans consists of 10 different members. The protein
      forms large oligomeric complexes, containing up to 40 or more subunits, which in
      vivo consist of heterooligomeric complexes formed by a mixture of alphaB
      crystallin and other sHsps. alphaB-crystallin is highly expressed in the lens and
      to a lesser extent in several other tissues, among which heart, skeletal muscle
      and brain. alphaB-crystallin plays a role in several cellular processes, such as
      signal transduction, protein degradation, stabilization of cytoskeletal
      structures and apoptosis. Mutations in the alphaB-crystallin gene can have
      detrimental effects, leading to pathologies such as cataract and cardiomyopathy.
      This review describes the biological roles of alphaB-crystallin, with a special
      focus on its function in the eye lens, heart muscle and brain. In addition its
      therapeutic potential is discussed. 

PMID- 24576799
TI  - Management of hypotension in preterm infants (The HIP Trial): a randomised
      controlled trial of hypotension management in extremely low gestational age
      newborns.
AB  - BACKGROUND: Extremely preterm babies (delivered at <28 completed weeks of
      gestation) are frequently diagnosed with hypotension and treated with inotropic
      and pressor drugs in the immediate postnatal period. Dopamine is the most
      commonly used first-line drug. Babies who are treated for hypotension more
      frequently sustain brain injury, have long-term disability or die compared to
      those who are not. Despite the widespread use of drugs to treat hypotension in
      such infants, evidence for efficacy is lacking, and the effect of these agents on
      long-term outcomes is unknown. HYPOTHESIS: In extremely preterm babies,
      restricting the use of dopamine when mean blood pressure (BP) values fall below a
      nominal threshold and using clinical criteria to determine escalation of support
      ('restricted' approach) will result in improved neonatal and longer-term
      developmental outcomes. RESEARCH PLAN: In an international multi-centre
      randomised trial, 830 infants born at <28 weeks of gestation, and within 72 h of
      birth, will be allocated to 1 of 2 alternative treatment options (dopamine vs.
      restricted approach) to determine the better strategy for the management of BP,
      using a conventional threshold to commence treatment. The first co-primary
      outcome of survival without brain injury will be determined at 36 weeks'
      postmenstrual age and the second co-primary outcome (survival without
      neurodevelopmental disability) will be assessed at 2 years of age, corrected for
      prematurity. DISCUSSION: It is essential that appropriately designed trials be
      performed to define the most appropriate management strategies for managing low
      BP in extremely preterm babies.

PMID- 24576801
TI  - Catastrophic brain relapse in seronegative NMO after a single dose of
      natalizumab.
AB  - Natalizumab, an effective treatment for MS, has been shown to exacerbate
      neuromyelitis optica (NMO) with aquaporin-4 antibodies, but whether this is the
      case in antibody negative NMO and atypical MS/NMO spectrum disorder overlap
      syndromes is unknown. We describe a patient with a relapsing optico-spinal
      demyelinating syndrome, negative for aquaporin-4 antibodies, who experienced a
      catastrophic brain relapse shortly after a single dose of natalizumab,
      highlighting that MS immunomodulatory drugs may worsen demyelination in patients
      with seronegative NMO and atypical MS/NMO overlap syndromes even if they are
      aquaporin-4 antibody negative. We summarise the treatments considered safe and
      effective in NMO, and those with potential to exacerbate disease. 

PMID- 24576800
TI  - Novel methodology to evaluate renal cysts in polycystic kidney disease.
AB  - AIM: To develop and assess a semiautomated method for segmenting and counting
      individual renal cysts from mid-slice MR images in patients with autosomal
      dominant polycystic kidney disease (ADPKD). METHODS: A semiautomated method was
      developed to segment and count individual renal cysts from mid-slice MR images in
      241 subjects with ADPKD from the Consortium for Radiologic Imaging Studies of
      Polycystic Kidney Disease. For each subject, a mid-slice MR image was selected
      from each set of coronal T2-weighted MR images covering the entire kidney. The
      selected mid-slice image was processed with the semiautomated method to segment
      and count individual renal cysts. The number of cysts from the mid-slice image of
      each kidney was also measured by manual counting. The level of agreement between
      the semiautomated and manual cyst counts was compared using intraclass
      correlation (ICC) and a Bland-Altman plot. RESULTS: Individual renal cysts were
      successfully segmented using the semiautomated method in all 241 cases. The
      number of cysts in each kidney measured with the semiautomated and manual
      counting methods correlated well (ICC = 0.96 for the right or left kidney), with
      a small average difference (-0.52, with higher semiautomated counts, for the
      right kidney, and 0.13, with higher manual counts, for the left kidney) in the
      semiautomated method. However, there was substantial variation in a small number
      of subjects; 6 of 241 participants (2.5%) had a difference in the total cyst
      count of more than 15. CONCLUSION: We have developed a semiautomated method to
      segment individual renal cysts from mid-slice MR images in ADPKD kidneys as a
      quantitative indicator of characterization and disease progression of ADPKD.

PMID- 24576802
TI  - HLA-DRB1 15:01 and Epstein-Barr virus in a multiple sclerosis patient with
      psoriasis, nasopharyngeal and breast cancers. Lessons for possible hidden links
      for autoimmunity and cancer.
AB  - BACKGROUND: Multiple sclerosis (MS) patients have a low general cancer risk and
      cases of neoplastic comorbidity are attributed by many researchers in chance, or
      therapeutical side-effects. Human leucocyte antigen (HLA) class II allele DRB1
      15:01 is considered the main genetic factor independently associated with
      increased susceptibility for MS in Caucasians. Epstein-Barr virus (EBV) has also
      been proven to be a core triggering factor in MS initiation and progress, mainly
      in HLA-DRB1 15:01 positive MS patients. CASE REPORT: We present an exceptional
      case of a Greek-origin woman, carrying a distinct immunogenetic profile (HLA-A
      26:01-Cw 06:02-DRB1 15:01), which gradually developed psoriasis, nasopharyngeal
      carcinoma (NPC), MS, breast cancer, uterine leiomyoma and other neoplasms.
      DISCUSSION: EBV plays a fundamental role in the pathogenesis of both autoimmunity
      (i.e. MS) and cancer (i.e. NPC). Our patient's immunogenetic profile included HLA
      alleles which are associated with psoriasis (Cw 06:02), NPC (A 26:01), MS (DRB1
      15:01) and increased risk of MS, in patients carrying EBV (DRB1 15:01). We made a
      targeted review of the literature finding data supporting an EBV-HLA interaction
      mechanism behind our patient's unique combination of disorders, suggesting that
      beyond the standard role of each factor, their combination could act as the
      hidden link, in initiation or/and comorbidity of autoimmunity and cancer.

PMID- 24576803
TI  - The impact of stroke on cognitive processing - a prospective event-related
      potential study.
AB  - BACKGROUND AND PURPOSE: Stroke is often associated with cognitive decline which
      can be evaluated by event-related potentials (ERP). So far, only little is known
      about the impact of stroke on ERP. The aim of this prospective study was to
      follow-up ERP latencies in stroke patients and to evaluate the influence of sex,
      vascular territory of stroke, reinfarction, and secondary prevention
      (acetylsalicylic acid versus piracetam). METHODS: Visually evoked ERP were
      recorded in 563 stroke patients at baseline (i.e., within four weeks after
      stroke), after 12 months, and after 24 months. The latencies of the P2, N2, and
      P3 components were assessed and compared between different subgroups. RESULTS:
      The P3 latency is initially more increased in female stroke patients, but shows a
      better recovery in women compared to men. A secondary prevention with piracetam
      leads to a significantly better recovery of ERP latencies than a treatment with
      acetylsalicylic acid. Data suggests a better recovery of left hemispheric
      infarction compared to right hemispheric infarction. Patients, who suffered
      another stroke during the follow-up period, showed a prolongation of P3 latency,
      suggesting an increased P3 latency to be associated with reinfarction.
      CONCLUSIONS: Our results suggest that ERP measurement is an appropriate method
      for diagnosis and follow-up of cognitive changes after ischemic stroke. In
      particular the P3 component is an indicator for patients at risk for
      reinfarction.

PMID- 24576804
TI  - A star-shaped porphyrin-arginine functionalized poly(L-lysine) copolymer for
      photo-enhanced drug and gene co-delivery.
AB  - The co-delivery of drug and gene has become the primary strategy in cancer and
      other disease therapy. To co-deliver hydrophobic drug and functional gene
      efficiently into tumor cells, a star-shaped copolymer (PP-PLLD-Arg) with a
      photochemical internalization effect consisting of a porphyrin (PP) core and
      arginine-functionalized poly(L-lysine) dendron (PLLD-Arg) arms has been designed,
      and used to co-deliver docetaxel (DOC) and MMP-9 shRNA plasmid for nasopharyngeal
      cancer therapy. It was found that PP-PLLD-Arg/MMP-9 nanocomplex showed the photo
      enhanced gene transfection efficiency in vitro, and could mediate a significant
      reduce of MMP-9 protein expression in HNE-1 cells. For co-delivery analysis, the
      obtained PP-PLLD-Arg/DOC/MMP-9 complexes could induce a more significant
      apoptosis than DOC or MMP-9 used only, and decreased invasive capacity of HNE-1
      cells. Moreover, the star-shaped copolymer exhibited better blood compatibility
      and lower cytotoxicity compared to PEI-25k in the hemolysis and MTT assays, and
      also showed a good biocompatibility in vivo. Therefore, PP-PLLD-Arg with suited
      irradiation is a promising non-toxic and photo-inducible effective drug and gene
      delivery strategy, which should be encouraged in tumor therapy.

PMID- 24576805
TI  - Responses of Staphylococcus aureus bacterial cells to nanocrystalline nickel
      nanostructures.
AB  - A broad range of human diseases are associated with bacterial infections, often
      initiated by specific adhesion of a bacterium to the target environment. Despite
      the significant role of bacterial adhesion in human infectious diseases, details
      and mechanisms of bacterial adhesion have remained elusive. Herein, we study the
      physical interactions between Staphylococcus aureus, a type of micro-organism
      relevant to infections associated with medical implants, and nanocrystalline (nc)
      nickel nanostructures with various columnar features, including solid core,
      hollow, x-shaped and c-shaped pillars. Scanning electron microscopy results show
      the tendency of these bacterial cells to attach to the nickel nanostructures.
      Moreover, unique single bacterium attachment characteristics were observed on
      nickel nanostructures with dimensions comparable to the size of a single
      bacterium. 

PMID- 24576807
TI  - An ER-fMRI study of Russian inflectional morphology.
AB  - The generation of regular and irregular past tense verbs has long been a testing
      ground for different models of inflection in the mental lexicon. Behavioral
      studies examined a variety of languages, but neuroimaging studies rely almost
      exclusively on English and German data. In our fMRI experiment, participants
      inflected Russian verbs and nouns of different types and corresponding nonce
      stimuli. Irregular real and nonce verbs activated inferior frontal and inferior
      parietal regions more than regular verbs did, while no areas were more activated
      in the opposite comparison. We explain this activation pattern by increasing
      processing load: a parametric contrast revealed that these regions are also more
      activated for nonce stimuli compared to real stimuli. A very similar pattern is
      found for nouns. Unlike most previously obtained results, our findings are more
      readily compatible with the single-system approach to inflection, which does not
      postulate a categorical difference between regular and irregular forms. 

PMID- 24576806
TI  - The neural basis of sublexical speech and corresponding nonspeech processing: a
      combined EEG-MEG study.
AB  - We addressed the neural organization of speech versus nonspeech sound processing
      by investigating preattentive cortical auditory processing of changes in five
      features of a consonant-vowel syllable (consonant, vowel, sound duration,
      frequency, and intensity) and their acoustically matched nonspeech counterparts
      in a simultaneous EEG-MEG recording of mismatch negativity (MMN/MMNm). Overall,
      speech-sound processing was enhanced compared to nonspeech sound processing. This
      effect was strongest for changes which affect word meaning (consonant, vowel, and
      vowel duration) in the left and for the vowel identity change in the right
      hemisphere also. Furthermore, in the right hemisphere, speech-sound frequency and
      intensity changes were processed faster than their nonspeech counterparts, and
      there was a trend for speech-enhancement in frequency processing. In summary, the
      results support the proposed existence of long-term memory traces for speech
      sounds in the auditory cortices, and indicate at least partly distinct neural
      substrates for speech and nonspeech sound processing. 

PMID- 24576808
TI  - Neurophysiology of spectrotemporal cue organization of spoken language in
      auditory memory.
AB  - Listeners assign different weights to spectral dynamics, such as formant rise
      time (FRT), and temporal dynamics, such as amplitude rise time (ART), during
      phonetic judgments. We examined the neurophysiological basis of FRT and ART
      weighting in the /ba/-/wa/ contrast. Electroencephalography was recorded for
      thirteen adult English speakers during a mismatch negativity (MMN) design using
      synthetic stimuli: a /ba/ with /ba/-like FRT and ART; a /wa/ with /wa/-like FRT
      and ART; and a /ba/(wa) with /ba/-like FRT and /wa/-like ART. We hypothesized
      that because of stronger reliance on FRT, subjects would encode a stronger memory
      trace and exhibit larger MMN during the FRT than the ART contrast. Results
      supported this hypothesis. The effect was most robust in the later portion of
      MMN. Findings suggest that MMN is generated by multiple sources, differentially
      reflecting acoustic change detection (earlier MMN, bottom-up process) and
      perceptual weighting of ART and FRT (later MMN, top-down process). 

PMID- 24576809
TI  - Multi-armed poly(L-glutamic acid)-graft-polypropyleneinime as effective and serum
      resistant gene delivery vectors.
AB  - A new series of multi-armed MP-g-PPI dendrimers were synthesized by
      polymerization of BLG-NCA using G2.0PPI as macromolecular initiator and
      subsequent aminolysis with G1.0PPI or G2.0PPI. The chemical structure and
      composition of the MP-g-PPI dendrimers were characterized by Fourier transform
      infrared spectroscopy (FT-IR) and nuclear magnetic resonance spectroscopy ((1)H
      NMR). The MP-g-PPI showed a great ability to combine with pDNA to form complexes,
      which protect the pDNA from nuclease degradation. Dynamic light scattering (DLS)
      measurement illustrated that the sizes of complexes were in range of 111-219 nm.
      The transmission electron microscope (TEM) and atomic force microscope (AFM)
      observation showed that the morphology of these complexes was spherical. The MTT
      assay demonstrated that cytotoxicity of the MP-g-PPI was lower than that of PEI
      25K. The in vitro transfection test indicated that MP-g-PPI gene vectors
      displayed relative high transfection efficiency than that of PEI 25K and
      Lipofectamine 2000 in serum-containing medium. Furthermore, MP-g-PPI at the
      weight ratio of 7.5 displayed better serum-resistant capability than that of PEI
      25K and Lipofectamine 2000. The above facts revealed that multi-armed MP-g-PPI
      dendrimers may be promising gene vectors with low cytotoxicity, high transfection
      efficiency and serum-resistant ability.

PMID- 24576810
TI  - Preparation of osthole-polymer solid dispersions by hot-melt extrusion for
      dissolution and bioavailability enhancement.
AB  - The aim of this study was to investigate the potential of solid dispersion to
      improve the dissolution rate and bioavailability of osthole (Ost), a coumarin
      derivative with various pharmacological activities but with poor aqueous
      solubility. In present studies, the Ost solid dispersions were prepared with
      various polymers including Plasdone S-630, HPMC-E5, Eudragit EPO, and Soluplus by
      hot-melt extrusion method. In vitro characterizations were performed with
      differential scanning calorimetry (DSC), X-ray powder diffraction (XPRD), Fourier
      transform infrared (FT-IR) spectroscopy, and in vitro dissolution studies. In
      addition, in vivo pharmacokinetic studies of Ost solid dispersions were also
      conducted in rats after a single oral dose. In comparison to the untreated Ost
      coarse powder and the physical mixture with polymers, the solid dispersions
      prepared with Plasdone S-630 or HPMC-E5 (drug/polymer: 1:6) showed a significant
      enhancement of dissolution rate (~3-fold higher D30). In addition, such
      preparations exhibited a significantly decreased Tmax, ~5-fold higher Cmax and
      ~1.4-fold higher AUC when comparing with Ost coarse powder. In conclusion, solid
      dispersion prepared with appropriate polymer could serve as a promising
      formulation approach to enhance the dissolution rate and hence oral
      bioavailability of Ost. 

PMID- 24576811
TI  - Post-purchase reassessment and improvement of neuroendoscope holder: importance
      of physician-manufacturer communication.
AB  - BACKGROUND: Modern medical management requires constant quality improvement of
      the various instruments used for surgical procedures. Higher quality, less
      complicated handling, and reduced maintenance are all desirable qualities.
      However, any improvements in instrumentation require that surgeons must clearly
      understand the application of the device by adherence to the manufacturer's
      instructions. The weakness of this one-way information flow depends on the low
      interest among medical personnel for post-purchase reassessment. OBJECTIVE:
      Service industries have research departments to investigate the post-purchase
      behavior of customers, and service recovery is considered essential to retain
      customers after service failure. All service providers can suffer service
      failures, and even the best providers may make errors in delivering service. Such
      an approach has been increasingly adopted in the risk management at medical
      institutions. METHODS: We report our clinical trials of the post-purchase
      reassessment and product improvement of surgical instrumentation. Medical
      personnel reassessed the use of a newly developed endoscope holder based on the
      manufacturer's manual and made recommendations for possible improvements, which
      were examined by the manufacturer. RESULTS: Simple but important improvement was
      achieved for reducing the instability and uncertainty of instrument fixation.
      CONCLUSION: This bi-directional post-purchase communication between medical
      personnel and manufacturers can improve risk management in medical institutions.

PMID- 24576812
TI  - Activity aware energy efficient priority based multi patient monitoring adaptive
      system for body sensor networks.
AB  - BACKGROUND: According to WHO, Cardiovascular diseases are the major cause of
      death worldwide. Due to the increase in cardiac diseases, miniaturized and energy
      efficient remote cardiac monitoring systems are required. OBJECTIVE: To develop
      an Activity Aware Energy Efficient priority based Multi Patient Monitoring
      protocol for Body Sensor Networks to monitor physiological signals continuously.
      The protocol must also be adaptive to allow for new connections and to
      renegotiate the nodes services. METHOD: In this protocol, the ECG signals of
      multiple patients are monitored one after another in a cyclic order. Slots are
      allotted to each patient by means of a dynamic TDMA scheme where the slot
      duration is dependent upon the criticality of the patient. A Network
      configuration slot is provided at the end of each frame to reconfigure the
      network. Using the wearer's activity level, the sensor dynamically manages its
      activities namely, sampling of the ECG sensor, processing of the data, and
      wireless transmission to minimize overall power consumption. Additional energy
      efficiency is achieved by assigning priorities to the devices connected in the
      network and turning them on and off periodically based on their priorities.
      RESULTS: The protocol is implemented on Shimmer nodes and ECG signals of N
      patients are monitored. The reconfiguration of the node's priority and sampling
      rate based on the health condition of the patient are demonstrated. A comparison
      of energy consumption, packet delivery ratio and battery life time is made.
      CONCLUSIONS: Energy consumption and nodes lifetime are the parameters to be
      optimized in the case of BSN. The AAEEPMPM protocol for BSN has been designed and
      implemented in hardware platform for energy efficiency. The results obtained from
      the BSN shows that this protocol has higher energy efficiency and provides better
      lifetime for the network.

PMID- 24576813
TI  - Cardiopulmonary performance testing using a robotics-assisted tilt table:
      feasibility assessment in able-bodied subjects.
AB  - BACKGROUND: Robotics-assisted tilt table technology was introduced for early
      rehabilitation of neurological patients. It provides cyclical stepping movement
      and physiological loading of the legs. The aim of the present study was to assess
      the feasibility of this type of device for peak cardiopulmonary performance
      testing using able-bodied subjects. METHODS: A robotics-assisted tilt table was
      augmented with force sensors in the thigh cuffs and a work rate estimation
      algorithm. A custom visual feedback system was employed to guide the subjects'
      work rate and to provide real time feedback of actual work rate. Feasibility
      assessment focused on: (i) implementation (technical feasibility), and (ii)
      responsiveness (was there a measurable, high-level cardiopulmonary reaction?).
      For responsiveness testing, each subject carried out an incremental exercise test
      to the limit of functional capacity with a work rate increment of 5 W/min in
      female subjects and 8 W/min in males. RESULTS: 11 able-bodied subjects were
      included (9 male, 2 female; age 29.6 +/- 7.1 years: mean +/- SD). Resting oxygen
      uptake (O<formula>_{2}</formula>) was 4.6 +/- 0.7 mL/min/kg and
      O<formula>_{2}</formula>peak was 32.4 +/- 5.1 mL/min/kg; this mean
      O<formula>_{2}</formula>peak was 81.1% of the predicted peak value for cycle
      ergometry. Peak heart rate (HRpeak) was 177.5 +/- 9.7 beats/min; all subjects
      reached at least 85% of their predicted HRpeak value. Respiratory exchange ratio
      (RER) at O<formula>_{2}</formula>peak was 1.02 +/- 0.07. Peak work rate) was 61.3
      +/- 15.1 W. All subjects reported a Borg CR10 value for exertion and leg fatigue
      of 7 or more. CONCLUSIONS: The robotics-assisted tilt table is deemed feasible
      for peak cardiopulmonary performance testing: the approach was found to be
      technically implementable and substantial cardiopulmonary responses were
      observed. Further testing in neurologically-impaired subjects is warranted.

PMID- 24576814
TI  - The mGlu5 receptor regulates extinction of cocaine-driven behaviours.
AB  - BACKGROUND: There is extensive evidence implicating the metabotropic glutamate 5
      (mGlu5) receptor in aspects of addiction-related behaviours. METHODS: Here, we
      used a well-characterized line of mGlu5-deficient mice to further examine the
      role of this receptor in cocaine-driven behaviours. We confirmed the previously
      reported deficit in hippocampal long-term potentiation and associated spatial
      learning impairment. RESULTS: Despite a spatial learning deficit, mGlu5-deficient
      mice developed and maintained a conditioned place preference to cocaine,
      suggesting cocaine reward and Pavlovian conditioning are intact in these animals.
      Notably, however, mGlu5-deficient mice exhibited a marked deficit in the
      extinction of a cocaine-conditioned place preference compared to wild type
      littermates. Moreover, in a fixed ratio operant intravenous self-administration
      paradigm, both genotypes showed similar responding for cocaine over two different
      doses, while mGlu5-deficient mice displayed enhanced responding on a progressive
      ratio schedule. In addition, cue-induced drug-seeking after abstinence was
      exaggerated in mGlu5-deficient mice. CONCLUSION: Collectively, these findings
      suggest that while the mGlu5 receptor may be involved in mediating the rewarding
      effects of cocaine, it appears necessary for the extinction of cocaine-driven
      behaviours.

PMID- 24576817
TI  - Route selection in action imitation: a matter of strategic choice?

PMID- 24576818
TI  - Apraxia and the representation of knowledge: where is the boundary between the
      cognitive and the motor domain?

PMID- 24576816
TI  - Developmental and adult GAP-43 deficiency in mice dynamically alters hippocampal
      neurogenesis and mossy fiber volume.
AB  - Growth-associated protein-43 (GAP-43) is a presynaptic protein that plays key
      roles in axonal growth and guidance and in modulating synapse formation. Previous
      work has demonstrated that mice lacking one allele of this gene (GAP-43+/- mice)
      exhibit hippocampal structural abnormalities, impaired spatial learning and
      stress-induced behavioral withdrawal and anxiety, behaviors that are dependent on
      proper hippocampal circuitry and function. Given the correlation between
      hippocampal function, synaptic connectivity and neurogenesis, we tested if
      behaviorally naive GAP-43+/- mice had alterations in either neurogenesis or
      synaptic connectivity in the hippocampus during early postnatal development and
      young adulthood, and following behavior testing in older adults. To test our
      hypothesis, we examined hippocampal cell proliferation (Ki67), number of immature
      neuroblasts (doublecortin, DCX) and mossy fiber volume (synaptoporin) in
      behaviorally naive postnatal day 9 (P9) and P26, and behaviorally experienced 5-
      to 7-month-old GAP-43+/- and +/+ littermate mice. P9 GAP-43+/- mice had fewer
      Ki67+ and DCX+ cells compared to +/+ mice, particularly in the posterior dentate
      gyrus, and smaller mossy fiber volume in the same region. In young adulthood,
      however, male GAP-43+/- mice had more Ki67+ and DCX+ cells and greater mossy
      fiber volume in the posterior dentate gyrus relative to male +/+ mice. These
      increases were not seen in females. In 5- to 7-month-old GAP-43+/- mice (whose
      behaviors were the focus of our prior publication), there was no global change in
      the number of proliferating or immature neurons relative to +/+ mice. However,
      more detailed analysis revealed fewer proliferative DCX+ cells in the anterior
      dentate gyrus of male GAP-43+/- mice compared to male +/+ mice. This reduction
      was not observed in females. These results suggest that young GAP-43+/- mice have
      decreased hippocampal neurogenesis and synaptic connectivity, but slightly older
      mice have greater hippocampal neurogenesis and synaptic connectivity. In
      conjunction with our previous study, these findings suggest that GAP-43 is
      dynamically involved in early postnatal and adult hippocampal neurogenesis and
      synaptic connectivity, possibly contributing to the GAP-43+/- behavioral
      phenotype.

PMID- 24576819
TI  - Metabolic flux redirection from a central metabolic pathway toward a synthetic
      pathway using a metabolic toggle switch.
AB  - Overexpression of genes in production pathways and permanent knockout of genes in
      competing pathways are often employed to improve production titer and yield in
      metabolic engineering. However, the deletion of a pathway responsible for growth
      and cell maintenance has not previously been employed, even if its competition
      with the production pathway is obvious. In order to optimize intracellular
      metabolism at each fermentation phase for bacterial growth and production, a
      methodology employing conditional knockout is required. We constructed a
      metabolic toggle switch in Escherichia coli as a novel conditional knockout
      approach and applied it to isopropanol production. The resulting redirection of
      excess carbon flux caused by interruption of the TCA cycle via switching gltA OFF
      improved isopropanol production titer and yield up to 3.7 and 3.1 times,
      respectively. This approach is a useful tool to redirect carbon flux responsible
      for bacterial growth and/or cell maintenance toward a synthetic production
      pathway. 

PMID- 24576820
TI  - Achieving energy goals at day 4 after admission in critically ill children;
      predictive for outcome?
AB  - BACKGROUND & AIMS: Adequate nutritional intake is essential during pediatric
      intensive care admission. We investigated whether achievement of energy intake
      goals at day 4 after admission and route of nutrition were associated with
      improved outcome. METHODS: Observational study using prospectively acquired data.
      Patients receiving enteral and/or parenteral nutrition were included. The energy
      intake target range at day 4 after admission was 90-110% of resting energy
      expenditure +10%. Acute malnutrition was defined as weight-for-age <-2 SD.
      Clinical outcome measures were length of stay, days on ventilator, duration of
      antibiotics and number of new infections. Data as median (min-max). RESULTS: Of
      325 subjects (age 0.14 (0.0-18.0) year), 19% were acutely malnourished upon
      admission. Median 86% of energy goals were administered via the enteral route.
      With enteral energy intake, 7% of patients were fed within the target range, 50%
      were fed below and 43% were fed above the target range. In a subgroup (n = 223)
      the acutely malnourished proportion at discharge (26%) was not significantly
      different from that upon admission (22%). Whether the energy intake was below,
      within or above the target range did not affect changes in clinical outcome, nor
      did the route of nutrition. CONCLUSIONS: Acute malnutrition was highly prevalent
      upon admission and at discharge. With our nutritional protocol we achieved high
      rates of (enteral) energy intake. A high percentage of our population received
      enteral energy above the target energy range. However, there was no association
      between the amount of energy intake or route of nutrition and clinical outcome.

PMID- 24576821
TI  - Embedding fluorescent mesoporous silica nanoparticles into biocompatible nanogels
      for tumor cell imaging and thermo/pH-sensitive in vitro drug release.
AB  - Thermo/pH-sensitive/fluorescent/biocompatible nanospheres consisting of quantum
      dots-embedded mesoporous silica nanoparticles (Q-MS) as a core and poly(N
      isopropylacrylamide (NIPAM))-graft-chitosan (CS) nanogels as a shell (PNIPAM-g
      CS) were prepared via temperature-regulated one-pot copolymerization of NIPAM
      monomer and CS in the presence of Q-MS. The prepared nanospheres exhibited
      remarkable fluorescence/thermo/pH-sensitivity. HepG2 cells treated with
      nanospheres displayed bright fluorescence imaging. Loading efficiency and
      capacity of Doxorubicin (Dox) into nanospheres were regularly increased with the
      increment of Dox concentration. At a high temperature and a low pH, cumulative in
      vitro release of Dox from Dox-loaded nanospheres was much great and fast.
      Released Dox still retained high anticancer activity, and blank nanosphere
      carriers produced neglectful toxicity to HepG2 cells. The multifunctional
      nanospheres could be further developed toward temperature/pH-regulated drug
      carriers for in vivo tumor therapy with a rapid drug release and fluorescence
      imaging in targeted tissues.

PMID- 24576822
TI  - A study of double stranded DNA adsorption on aluminum surface by means of
      electrochemical impedance spectroscopy.
AB  - Immobilization of DNA on the solid surfaces is one of the goals in bio- and nano
      technologies. Adsorption of double stranded DNA on the surface of aluminum was
      electrochemically studied by means of impedance spectroscopy. Nyquist diagram of
      aluminum in a tris (hydroxymethyl) ammoniummethane-HCl (Tris-HCl) buffer
      solution, pH 7.4 consisted of two overlapped capacitive semicircles. The high
      frequency semicircle was related to the passivity of Cl(-)-containing aluminum
      species in the oxide layer, and low-frequency semicircle was attributed to metal
      dissolution. When DNA was added to the Tris-HCl buffer solution, Nyquist diagrams
      represented an inductive loop at low frequencies due to the adsorption of DNA on
      the pre-covered aluminum surface by hydroxy-contained species. The DNA adsorption
      on the aluminum surface was also confirmed by X-ray photoelectron spectroscopy.
      Open circuit potential variation with time also indicated the chemical adsorption
      of DNA on the aluminum surface.

PMID- 24576823
TI  - Association between nutrient intake and anemia in Brazilian adolescents.
AB  - AIMS: The association between the intake of iron, vitamins A and C and calcium
      and the prevalence of anemia and hemoglobin (Hb) levels was investigated in
      adolescents. METHODS: A cross-sectional study was developed with 529 Brazilian
      students. Anemia was defined in terms of Hb concentration. Nutrient intake was
      assessed by a 3-day food record. The association between the prevalence of
      inadequate nutrient intake and anemia was estimated by the chi(2) test, and that
      between nutrient intake and Hb by linear regression. RESULTS: The prevalence of
      inadequate nutrient intake did not differ between nonanemic and anemic subjects.
      Anemic adolescents had a lower mean intake of iron than nonanemic adolescents.
      Among boys aged 11-13 years, the anemic subjects had lower vitamin C intake than
      those who were nonanemic (41.1 vs. 62.6 mg, p < 0.01), and among those aged 14-19
      years, there was a tendency for a positive association between Hb and heme iron
      intake (beta = 0.64, p = 0.06) and a negative association with calcium intake
      (beta = -0.003, p = 0.02). In females, daily nutrient intake did not differ
      between anemic and nonanemic individuals. CONCLUSIONS: Heme iron and vitamin C
      are possible protective factors against anemia in boys. However, the lack of
      association between inadequate iron intake and anemia, especially in girls,
      suggests that other factors beyond diet could explain anemia in this age range.

PMID- 24576824
TI  - Antibiotic prophylaxis for preventing recurrent cellulitis: a systematic review
      and meta-analysis.
AB  - IMPORTANCE: A significant proportion of patients who have had a first episode of
      erysipelas or uncomplicated cellulitis will subsequently develop a recurrence.
      There is disagreement about how effective antibiotic prophylaxis is for
      preventing recurrent cellulitis. OBJECTIVE: To determine if antibiotic
      prophylaxis is effective in preventing recurrent cellulitis compared to no
      prophylaxis using a systematic review and meta-analysis. DATA SOURCES: Studies in
      any language identified by searching Medline, EMBASE, Cochrane Library, CINAHL,
      TRIP database, clinical practice guidelines websites, and ongoing trials
      databases up to 31st August 2012. Search terms included cellulitis, erysipelas,
      controlled clinical trial, randomized, placebo, clinical trials, randomly, and
      trial. STUDY SELECTION: Only controlled trials comparing antibiotic prophylaxis
      to no antibiotic prophylaxis in patients age 16 years and above, and after 1 or
      more episodes of cellulitis, were included. DATA EXTRACTION AND SYNTHESIS:
      Independent extraction of articles was done by 2 investigators using predefined
      data extraction templates, including study quality indicators. PROSPERO
      registration number: CRD42012002528. Meta-analyses were done using random-effects
      models. MAIN OUTCOMES AND MEASURES: The primary outcome was the number of
      patients with a recurrence of cellulitis. Secondary outcomes were (1) the time to
      next episode of recurrence, (2) quality of life measures, and (3) adverse events
      (e.g. allergic reactions, nausea). RESULTS: Five randomized controlled trials (n
      = 535), with 260 patients in the intervention arm and 275 in the comparator group
      met our inclusion criteria. 44 patients (8%) in the antibiotic prophylaxis group
      and 97 patients (18%) in the comparator group had an episode of cellulitis.
      Antibiotic prophylaxis significantly reduced the number of patients having
      recurrent cellulitis, with a risk ratio (RR) of 0.46 (95% CI 0.26-0.79). None of
      the studies reported severe adverse effects to antibiotics. There was
      methodological heterogeneity amongst the studies in terms of types of antibiotic
      used, delivery modes, number of recurrences of cellulitis at study entry, and
      study quality. CONCLUSION AND RELEVANCE: Antibiotic prophylaxis can prevent
      recurrent cellulitis. Future research should aim to identify the ideal type,
      dosage, and duration of antibiotics for prophylaxis, as well as to identify the
      group of patients who will benefit most from antibiotic prophylaxis.

PMID- 24576825
TI  - Decreasing incidence rates of bacteremia: a 9-year population-based study.
AB  - BACKGROUND: Numerous studies have shown that the incidence rate of bacteremia has
      been increasing over time. However, few studies have distinguished between
      community-acquired, healthcare-associated and nosocomial bacteremia. METHODS: We
      conducted a population-based study among adults with first-time bacteremia in
      Funen County, Denmark, during 2000-2008 (N = 7786). We reported mean and annual
      incidence rates (per 100,000 person-years), overall and by place of acquisition.
      Trends were estimated using a Poisson regression model. RESULTS: The overall
      incidence rate was 215.7, including 99.0 for community-acquired, 50.0 for
      healthcare-associated and 66.7 for nosocomial bacteremia. During 2000-2008, the
      overall incidence rate decreased by 23.3% from 254.1 to 198.8 (3.3% annually, p <
      .001), the incidence rate of community-acquired bacteremia decreased by 25.6%
      from 119.0 to 93.8 (3.7% annually, p < .001) and the incidence rate of nosocomial
      bacteremia decreased by 28.9% from 82.2 to 56.0 (4.2% annually, p < .001). The
      incidence rate of healthcare-associated bacteremia remained stable. The most
      common microorganisms were Escherichia coli (28.3%), Staphylococcus aureus
      (12.3%), coagulase-negative staphylococci (10.0%) and Streptococcus pneumoniae
      (9.1%). Regardless of place of acquisition, the proportion of bacteremias caused
      by enterococci increased (p < .05) and the proportion caused by coagulase
      negative staphylococci decreased (p < .05). CONCLUSIONS: The incidence rates of
      community-acquired and nosocomial bacteremia decreased substantially over time.

PMID- 24576826
TI  - Unique reassortant of influenza A(H7N9) virus associated with severe disease
      emerging in Hong Kong.
AB  - OBJECTIVE: Human infections caused by avian influenza virus A(H7N9) re-emerged in
      late 2013. We reported the first Hong Kong patient without risk factors for
      severe A(H7N9) disease. METHODS: Direct sequencing was performed on the
      endotracheal aspirate collected from a 36-year-old female with history of poultry
      contact. Bioinformatic analysis was performed to compare the current strain and
      previous A(H7N9) isolates. RESULTS: The influenza A/Hong Kong/470129/2013 virus
      strain was detected in a patient with acute respiratory distress syndrome,
      deranged liver function and coagulation profile, cytopenia, and rhabdomyolysis.
      The HA, NA and MP genes of A/Hong Kong/470129/2013 cluster with those of other
      human A(H7N9) strains. The PB1, PB2 and NS genes are most closely related to
      those of A/Guangdong/1/2013 strain identified in August 2013, but are distinct
      from those of other human and avian A(H7N9) strains. The other internal genes NP
      and PA genes are more closely related to those of non-A(H7N9) avian influenza A
      viruses. A unique PA L336M mutation, associated with increased polymerase
      activity, was found. The patient required salvage by extracorporeal membrane
      oxygenation. CONCLUSIONS: The A/Hong Kong/470129/2013 virus is a novel
      reassortant derived from A/Guangdong/1/2013 virus. The unique mutation PA L336M
      may enhance viral replication and therefore disease severity.

PMID- 24576827
TI  - A summary of the iodine supplementation study protocol (I2S2): a UK multicentre
      randomised controlled trial in preterm infants.
AB  - This paper summarises the study protocol for the randomised controlled trial of
      iodine supplementation in preterm infants. Iodine is essential for the synthesis
      of thyroxine, and thyroxine is essential for normal brain development in utero
      and for the first 2-3 years of life. The recommended iodine intake in parenteral
      nutrition regimens is 1 MUg/kg/day and commercially available parenteral
      solutions for infants reflect these recommendations. In the absence of other
      iodine sources, infants are vulnerable to negative iodine balance and
      insufficiency. As many preterm infants are fed parenterally for prolonged periods
      with solutions which have been shown to be iodine-deficient, the I2S2 Trial was
      designed to establish whether iodine supplementation of preterm infants benefits
      neurodevelopment.

PMID- 24576828
TI  - Autocrine motility factor modulates EGF-mediated invasion signaling.
AB  - Autocrine motility factor (AMF) enhances invasion by breast cancer cells, but how
      its secretion and effector signaling are controlled in the tumor microenvironment
      is not fully understood. In this study, we investigated these issues with a
      chimeric AMF that is secreted at high levels through a canonical endoplasmic
      reticulum (ER)/Golgi pathway. Using this tool, we found that AMF enhances tumor
      cell motility by activating AKT/ERK, altering actin organization, and stimulating
      beta-catenin/TCF and activating protein 1 transcription. EGF enhanced secretion
      of AMF through its casein kinase II-mediated phosphorylation. RNA interference
      mediated attenuation of AMF expression inhibited EGF-induced invasion by
      suppressing extracellular signal-regulated kinase signaling. Conversely,
      exogenous AMF overcame the inhibitory effect of EGF receptor inhibitor gefitinib
      on invasive motility by activating HER2 signaling. Taken together, our findings
      show how AMF modulates EGF-induced invasion while affecting acquired resistance
      to cytotoxic drugs in the tumor microenvironment.

PMID- 24576829
TI  - A specific STAT3-binding peptide exerts antiproliferative effects and antitumor
      activity by inhibiting STAT3 phosphorylation and signaling.
AB  - STAT3 promotes the survival, proliferation, metastasis, immune escape, and drug
      resistance of cancer cells, making its targeting an appealing prospect. However,
      although multiple inhibitors of STAT3 and its regulatory or effector pathway
      elements have been developed, bioactive agents have been somewhat elusive. In
      this report, we report the identification of a specific STAT3-binding peptide
      (APTSTAT3) through phage display of a novel "aptide" library. APTSTAT3 bound
      STAT3 with high specificity and affinity (~231 nmol/L). Addition of a cell
      penetrating motif to the peptide to yield APTSTAT3-9R enabled uptake by murine
      B16F1 melanoma cells. Treatment of various types of cancer cells with APTSTAT3-9R
      blocked STAT3 phosphorylation and reduced expression of STAT targets, including
      cyclin D1, Bcl-xL, and survivin. As a result, APTSTAT3-9R suppressed the
      viability and proliferation of cancer cells. Furthermore, intratumoral injection
      of APTSTAT3-9R exerted potent antitumor activity in both xenograft and allograft
      tumor models. Our results offer a preclinical proof-of-concept for APTSTAT3 as a
      tractable agent for translation to target the broad array of cancers harboring
      constitutively activated STAT3.

PMID- 24576830
TI  - Loss of NF1 in cutaneous melanoma is associated with RAS activation and MEK
      dependence.
AB  - Melanoma is a disease characterized by lesions that activate ERK. Although 70% of
      cutaneous melanomas harbor activating mutations in the BRAF and NRAS genes, the
      alterations that drive tumor progression in the remaining 30% are largely
      undefined. Vemurafenib, a selective inhibitor of RAF kinases, has clinical
      utility restricted to BRAF-mutant tumors. MEK inhibitors, which have shown
      clinical activity in NRAS-mutant melanoma, may be effective in other ERK pathway
      dependent settings. Here, we investigated a panel of melanoma cell lines wild
      type for BRAF and NRAS to determine the genetic alteration driving their
      transformation and their dependence on ERK signaling in order to elucidate a
      candidate set for MEK inhibitor treatment. A cohort of the BRAF/RAS wild type
      cell lines with high levels of RAS-GTP had loss of NF1, a RAS GTPase activating
      protein. In these cell lines, the MEK inhibitor PD0325901 inhibited ERK
      phosphorylation, but also relieved feedback inhibition of RAS, resulting in
      induction of pMEK and a rapid rebound in ERK signaling. In contrast, the MEK
      inhibitor trametinib impaired the adaptive response of cells to ERK inhibition,
      leading to sustained suppression of ERK signaling and significant antitumor
      effects. Notably, alterations in NF1 frequently co-occurred with RAS and BRAF
      alterations in melanoma. In the setting of BRAF(V600E), NF1 loss abrogated
      negative feedback on RAS activation, resulting in elevated activation of RAS-GTP
      and resistance to RAF, but not MEK, inhibitors. We conclude that loss of NF1 is
      common in cutaneous melanoma and is associated with RAS activation, MEK
      dependence, and resistance to RAF inhibition.

PMID- 24576831
TI  - Diagnostic value of brain chronic black holes on T1-weighted MR images in
      clinically isolated syndromes.
AB  - BACKGROUND: Non-enhancing black holes (neBHs) are more common in multiple
      sclerosis (MS) patients with longer disease durations and progressive disease
      subtypes. OBJECTIVE: Our aim was to analyse the added value of neBHs in patients
      with clinically isolated syndromes (CISs) for predicting conversion to clinically
      definite MS (CDMS). METHODS: Patients were classified based on the presence or
      absence of neBHs and on the number of Barkhof-Tintore (B-T) criteria fulfilled.
      Dissemination in space (DIS) was defined as the presence of at least three of the
      four B-T criteria. Dissemination in time (DIT)1 was defined by simultaneous
      presence of enhancing and non-enhancing lesions. DIT2 was defined by simultaneous
      presence of neBHs and T2 lesions not apparent on T1-weighted images. RESULTS:
      Focal T2-hyperintense brain lesions were identified in 87.7% of the 520 CIS
      patients, and 41.4% of them presented at least one neBH. Patients meeting DIS,
      DIT1, and DIT2 had a significantly higher rate of conversion to CDMS. After
      adjusting for DIS, only patients who fulfilled DIT1 preserved a significant
      increase in CDMS conversion. CONCLUSIONS: Non-enhancing black holes in CIS
      patients are associated with a higher risk of conversion to CDMS. However, the
      predictive value of this finding is lost when added to the DIS criteria.

PMID- 24576832
TI  - Hospice agencies' hospital contract status and differing levels of hospice care.
AB  - In response to a 2011 finding that approximately 27% of Medicare-certified
      hospices do not provide a single day of general inpatient care (GIP), the authors
      explored the extent to which hospices have contracts with hospitals for GIP.
      Using the 2007 National Home and Hospice Care Survey, we estimated that 1119
      (32%) agencies had no contract with any hospitals in 2007 and half of those with
      no contract did not have a contract with a skilled nursing facility (SNF) either.
      As a result, these hospices were unable to provide GIP referrals for those in
      need of inpatient care for acute pain and symptom management. More importantly,
      not having a contract with a hospital was just one of the factors influencing GIP
      provision. In the multivariate logistic model, after controlling for contract
      status with a hospital and other hospice characteristics, agencies in the second
      quartile of hospice patient census (12-29 vs 73 or more, adjusted odds ratio =
      14.10; 95% confidence interval 4.26-46.62) were independently related to
      providing only routine home care. These hospices are more likely to rely solely
      on scatter beds for GIP provision. Given that a significant portion of hospices
      do not have a contract with a hospital, policy makers need to understand barriers
      to contracts with a hospital/SNF for GIP and consider a hospice's contract status
      as one of the standards for hospice certification. In addition, further research
      is necessary to understand why hospices that do have a contract with a hospital
      do not make GIP referral.

PMID- 24576833
TI  - Multiple Cardiopulmonary Resuscitation Attempts in a Community Hospital:
      Evaluation of the Futility Assessment.
AB  - BACKGROUND: In hospital settings, inadequate recognition of futility of
      aggressive medical management in patients with terminal disease and lack of the
      timely transition to palliative care may lead to both excessive and potentially
      harmful treatment and unnecessary burden on hospital resources. In order to
      better understand the outcomes of futile medical management and recognize the
      need for more appropriate end-of-life care, we evaluated the survival of
      particularly vulnerable cohort of patients in a community hospital who had
      survived at least 1 cardiorespiratory arrest (CRA) but whose medical problems led
      to subsequent arrests. METHODS: In this retrospective cohort study, we have
      reviewed the annual cardiopulmonary resuscitation (CPR) data in a community
      hospital in urban settings. RESULTS: Analyzing the population of all patients who
      had CRA, 22.4% had more than 1 CRA episode and had multiple CPRs (42% of all
      inpatient CPR were performed on this group of patients). Overall survival at the
      discharge of patients who had single CRA is significantly better than survival at
      the discharge of patients who had more than 1 CRA episode (31% vs 4.5%). Only
      18.5% of the patients who initially survived CPR after CRA were transitioned to
      "do not resuscitate" status subsequently, while vast majority had continued
      aggressive resuscitative efforts. CONCLUSION: Adjusting medical care based on
      futility assessment in patients with chronic illness who survive CRA is often
      neglected, but crucially relevant step in the optimization of health care system
      management.

PMID- 24576835
TI  - Morphologic predictors of a microbiological yield in patients with a tree-in-bud
      pattern on computed tomography.
AB  - PURPOSE: To evaluate the computed tomographic (CT) predictors of a clinically
      significant yield from microbiological tests in patients with a tree-in-bud
      pattern. MATERIALS AND METHODS: CT examinations in 53 patients (male=34; mean
      age=52.9 +/- 17.3 y) with a tree-in-bud pattern in whom a diagnostic test (sputum
      analysis, bronchoalveolar lavage or nasopharyngeal aspirates) had been performed
      within 2 weeks were identified. The following CT patterns were independently
      quantified by 2 thoracic radiologists: tree-in-bud, bronchiectasis, bronchial
      wall thickening, consolidation, ground-glass opacification, and nodules. The
      presence of cavitation (in nodules and/or consolidation) was recorded. Patient
      charts were reviewed for the presence of a clinically significant positive
      microbiological result. RESULTS: A clinically significant causal organism was
      present in 25/53 (47%) patients. The median extent of a tree-in-bud pattern was 5
      [range=1 to 16 (maximum range=0 to 18)], and cavitation was present in 14/53
      (26%) patients (cavitating nodules=8, cavitation in consolidation=3, and
      cavitation in consolidation and nodules=3). There was no independent linkage
      between the extent of a tree-in-bud pattern and the identification of a
      clinically significant organism. The microbiological yield was significantly
      higher if there was coexistent cavitation in nodules or consolidation [11/14
      (79%) vs. 14/39 (39%); P=0.005]. On stepwise logistic regression, the only CT
      predictor of a clinically significant microbiological yield was cavitation on CT
      (odds ratio=9.7; 95% confidence interval=1.9, 49.9; P<0.01); the extent of a tree
      in-bud pattern, concurrent use of antibiotics, age, and sex were not
      independently linked to a significant microbiological yield. CONCLUSIONS: A
      specific clinically significant microbiological diagnosis was obtained in
      approximately 50% of patients with a tree-in-bud pattern. The microbiological
      yield rises strikingly when a tree-in-bud pattern coexists with cavitation (in
      nodules or consolidation) but is not predicted by ancillary CT signs or clinical
      parameters.

PMID- 24576834
TI  - Contribution of bimodal hearing to lexical tone normalization in Mandarin
      speaking cochlear implant users.
AB  - Native Mandarin normal-hearing (NH) listeners can easily perceive lexical tones
      even under conditions of great voice pitch variations across speakers by using
      the pitch contrast between context and target stimuli. It is however unclear
      whether cochlear implant (CI) users with limited access to pitch cues can make
      similar use of context pitch cues for tone normalization. In this study, native
      Mandarin NH listeners and pre-lingually deafened unilaterally implanted CI users
      were asked to recognize a series of Mandarin tones varying from Tone 1 (high
      flat) to Tone 2 (mid-rising) with or without a preceding sentence context. Most
      of the CI subjects used a hearing aid (HA) in the non-implanted ear (i.e.,
      bimodal users) and were tested both with CI alone and CI + HA. In the test
      without context, typical S-shaped tone recognition functions were observed for
      most CI subjects and the function slopes and perceptual boundaries were similar
      with either CI alone or CI + HA. Compared to NH subjects, CI subjects were less
      sensitive to the pitch changes in target tones. In the test with context, NH
      subjects had more (resp. fewer) Tone-2 responses in a context with high (resp.
      low) fundamental frequencies, known as the contrastive context effect. For CI
      subjects, a similar contrastive context effect was found statistically
      significant for tone recognition with CI + HA but not with CI alone. The results
      suggest that the pitch cues from CIs may not be sufficient to consistently
      support the pitch contrast processing for tone normalization. The additional
      pitch cues from aided residual acoustic hearing can however provide CI users with
      a similar tone normalization capability as NH listeners.

PMID- 24576836
TI  - Computed tomography assessment of hemodynamic significance of coronary artery
      disease: CT perfusion, contrast gradients by coronary CTA, and fractional flow
      reserve review.
AB  - The need for functional estimation of the relevance of stenosis to guide
      appropriate treatment in coronary artery disease has recently been shown.
      Invasive coronary angiography (CA) with invasive measurement of the pressure
      gradient in patients with coronary stenoses becomes the method of choice for
      treatment decision-making in invasive cardiology. Coronary computed tomography
      angiography (CCTA) was established several years ago as a noninvasive alternative
      to invasive CA; it is used primarily to exclude coronary artery disease and has
      shown a very high negative predictive value in this regard. During the last
      several years, in an effort to obtain functional information, CCTA has received
      much attention. The rationale for this is that with the functional information
      provided by CT, the positive predictive value for "relevant" stenoses should be
      improved. In this article, the history and limitations of anatomic grading of
      coronary stenoses will be discussed. Furthermore, shifts in the treatment
      paradigm in modern cardiology will be introduced, as well as an overview of the
      currently used invasive methods to assess the "relevance" of stenosis. The
      current role and still-existing limitations of CCTA, as well as the systematic
      problems in comparing CA and CCTA, are addressed. As CCTA is a highly innovative
      technique, new innovations are currently under clinical evaluation, including
      myocardial perfusion imaging, attenuation gradient measurement, and assessment of
      fractional flow reserve with CT. This review article will mainly focus on the
      technical background of these techniques and the status of their clinical
      implementation and will attempt to provide some suppositions about the possible
      future role of these new innovations. 

PMID- 24576838
TI  - Cardiovascular function and flow by 4-dimensional magnetic resonance imaging
      techniques: new applications.
AB  - Acquisition techniques related to 4-dimensional (4D) flow magnetic resonance
      imaging (MRI) improved rapidly over the last 3 decades. Most importantly, a major
      improvement was the acceleration of the acquisition, which resulted in a
      clinically feasible scan duration and led to more comprehensive use of 4D flow
      MRI in clinical research. This resulted in several new applications of 4D flow
      MRI for the evaluation of various physiological and pathologic cardiovascular
      flow patterns. Visualization tools aim at displaying the direction and magnitude
      of blood flow velocity from 4D flow data, by using for instance a vector glyph or
      streamline representation or by constructing pathlines from particle tracing.
      Such tools are applied to provide insight in the temporal distribution of the 3D
      flow velocity and enable the quantification of hemodynamic markers. These
      hemodynamic markers play an important role in the quantitation of abnormalities
      in cardiovascular blood flow patterns and the characterization of vascular and
      myocardial remodelling, which can possibly be used to predict pathology such as
      heart failure, aortic dissection, or aneurysm or thrombus formation. This review
      focuses on the clinical use of 4D flow MRI and presents an overview of new
      applications of visualization and quantification tools to describe physiological
      and pathologic cardiovascular blood flow. 

PMID- 24576837
TI  - Myocardial tissue characterization by magnetic resonance imaging: novel
      applications of T1 and T2 mapping.
AB  - Cardiac magnetic resonance (CMR) imaging is a well-established noninvasive
      imaging modality in clinical cardiology. Its unsurpassed accuracy in defining
      cardiac morphology and function and its ability to provide tissue
      characterization make it well suited for the study of patients with cardiac
      diseases. Late gadolinium enhancement was a major advancement in the development
      of tissue characterization techniques, allowing the unique ability of CMR to
      differentiate ischemic heart disease from nonischemic cardiomyopathies. Using T2
      weighted techniques, areas of edema and inflammation can be identified in the
      myocardium. A new generation of myocardial mapping techniques are emerging,
      enabling direct quantitative assessment of myocardial tissue properties in
      absolute terms. This review will summarize recent developments involving T1
      mapping and T2-mapping techniques and focus on the clinical applications and
      future potential of these evolving CMR methodologies. 

PMID- 24576841
TI  - Extended-spectrum beta-lactamase, carbapenemase and AmpC producing
      Enterobacteriaceae in companion animals.
AB  - Organisms in the family Enterobactericeae including, Escherichia coli, commonly
      cause community and hospital-associated infections in both humans and companion
      animals. The increasing prevalence of infections with organisms producing broad
      spectrum beta-lactamses such as the ESBLs (particularly the CTX-M type), AmpC and
      carbapenemase enzymes are threatening the future of the beta-lactam drugs. While
      a number of organisms within the Enterobacteriaceae producing these enzymes have
      been isolated from cats, dogs and horses, E. coli, including isolates
      indistinguishable from strains found in people, has most frequently been
      described in the literature. Although little is known about the prevalence of
      colonization, or incidence of infections with these organisms in companion
      animals, the growing body of literature suggests that they are increasing.
      Transmission of these organisms to and from humans into companion animals has not
      been adequately described, although significant public and animal health concerns
      exist. 

PMID- 24576839
TI  - Small regulatory RNAs from low-GC Gram-positive bacteria.
AB  - Small regulatory RNAs (sRNAs) that act by base-pairing were first discovered in
      so-called accessory DNA elements--plasmids, phages, and transposons--where they
      control replication, maintenance, and transposition. Since 2001, a huge body of
      work has been performed to predict and identify sRNAs in a multitude of bacterial
      genomes. The majority of chromosome-encoded sRNAs have been investigated in E.
      coli and other Gram-negative bacteria. However, during the past five years an
      increasing number of sRNAs were found in Gram-positive bacteria. Here, we outline
      our current knowledge on chromosome-encoded sRNAs from low-GC Gram-positive
      species that act by base-pairing, i.e., an antisense mechanism. We will focus on
      sRNAs with known targets and defined regulatory mechanisms with special emphasis
      on Bacillus subtilis.

PMID- 24576842
TI  - Correlation between reported human infection with avian influenza A H7N9 virus
      and cyber user awareness: what can we learn from digital epidemiology?
AB  - Data on the topic of novel avian influenza A (H7N9) were collected based on the
      web analysis tool 'Baidu Index', a major Chinese search engine. We found a
      positive correlation between the volume of H7N9-related 'cyber user awareness'
      and the epidemic situation during the H7N9 outbreak in China (r=0.98, p<0.01,
      cumulative; r=0.43, p=0.018, daily) except in the early stage; the ranks of H7N9
      related topics changed at different epidemic stages. This study may improve our
      understanding of the role of web-based media in infectious disease surveillance
      in China. 

PMID- 24576840
TI  - Effects of AST-120 on blood concentrations of protein-bound uremic toxins and
      biomarkers of cardiovascular risk in chronic dialysis patients.
AB  - BACKGROUND: Removal of protein-bound uremic toxins by dialysis therapy is
      limited. The effect of oral adsorbent AST-120 in chronic dialysis patients has
      rarely been investigated. METHODS: AST-120 was administered 6.0 g/day for 3
      months in 69 chronic dialysis patients. The blood concentrations of indoxyl
      sulfate, p-cresol sulfate and biomarkers of cardiovascular risk were determined
      before and after AST-120 treatment. RESULTS: AST-120 significantly decreased both
      the total and free forms of indoxyl sulfate and p-cresol sulfate ranging from
      21.9 to 58.3%. There were significant simultaneous changes of the soluble tumor
      necrosis factor-like weak inducer of apoptosis (sTWEAK, 24% increase),
      malondialdehyde (14% decrease) and interleukin-6 (19% decrease). A significant
      association between the decrease of indoxyl sulfate and changes of sTWEAK and
      interleukin-6 was noted. CONCLUSIONS: AST-120 effectively decreased indoxyl
      sulfate and p-cresol sulfate levels in both total and free forms. AST-120 also
      improved the profile of cardiovascular biomarkers.

PMID- 24576843
TI  - Long-term outcomes of HIV-infected children in Thailand: the Thailand Pediatric
      HIV Observational Database.
AB  - OBJECTIVE: To describe the outcomes of antiretroviral therapy (ART) in a large
      cohort of HIV-infected children in Thailand. METHODS: The data were obtained from
      four collaborative referral sites around the country. Data from 2008 to March
      2011 were collected prospectively, and data before 2008 were collected
      retrospectively. RESULTS: Of the 1139 children, 599 (52.6%) were female, and the
      duration of ART was a median 2.9 years (interquartile range (IQR) 3.3-5.5 years).
      At ART initiation, the median age was 7.1 years (IQR 3.4-10.0 years), CD4
      percentage was 9.0% (IQR 3.0-17.0%), and 61.3% were in World Health Organization
      (WHO) stage 3 or 4. Seventy-four percent were initiated on an NNRTI-based
      regimen. The death and lost to follow-up rates were 1.3 (95% confidence interval
      (CI) 1.1-1.6) and 2.2 (95% CI 1.6-2.6)/100 patient-years of follow-up,
      respectively. At the last clinic visit of 919 children, the median CD4 percentage
      was 27.0% (IQR 23.0-32.0%) and 80.2% had HIV-RNA <40 copies/ml. WHO stage 1 or 2
      at ART initiation was associated with having a viral load <40 copies/ml (p <
      0.002), and baseline CD4 >=15% and starting with a three-drug regimen were
      associated with achieving CD4 >=25% (p<0.001). CONCLUSIONS: Although most
      children initiated ART at low CD4 levels, the majority achieved immune
      reconstitution and long-term virological control. Earlier treatment may improve
      these outcomes.

PMID- 24576844
TI  - A double-blind randomised controlled trial of fish oil-based versus soy-based
      lipid preparations in the treatment of infants with parenteral nutrition
      associated cholestasis.
AB  - BACKGROUND: Infants receiving prolonged parenteral nutrition (PN) are at risk of
      PN-associated cholestasis (PNAC). This can progress to hepatic failure and death
      if PN cannot be discontinued. Fish oil-based parenteral lipid preparation (FOLP)
      has been shown to be beneficial in case studies. OBJECTIVES: (1) To evaluate
      whether FOLP could halt or reverse the progression of PNAC compared with soy
      based parenteral lipid preparation (SLP) and (2) to assess the effects of FOLP on
      liver function and physical growth. METHODS:  DESIGN: double-blind randomised
      controlled trial. SETTING: level III neonatal intensive care unit. PARTICIPANTS:
      infants with PNAC (plasma-conjugated bilirubin concentration >= 34 umol/l or 2
      mg/dl) expected to be PN-dependent for >2 weeks. INTERVENTION: to receive either
      FOLP or SLP at 1.5 g/kg/day. PRIMARY OUTCOME MEASURE: reversal of PNAC within 4
      months after commencement of lipid treatment; secondary outcomes: rate of change
      of weekly liver function tests, infant growth parameters, blood lipid profile and
      episodes of late-onset sepsis. RESULTS: A total of 9 infants were randomised to
      the FOLP group and 7 to the SLP group. There was no significant difference in
      reversal of PNAC at 4 months between groups. Rates of increase of plasma
      conjugated bilirubin and alanine aminotransferase in the SLP group were
      significantly greater than the FOLP group (13.5 vs. 0.6 umol/l per week and 9.1
      vs. 1.1 IU/l per week, respectively, p = 0.03). Increased enteral nutrition was
      associated with significant improvement of PNAC in infants receiving FOLP
      compared with SLP (-8.5 vs. -1.6 umol/l per 10% increase in enteral nutrition,
      respectively). The study was terminated prematurely. CONCLUSIONS: progression of
      PNAC in PN-dependent infants can be halted by replacing SLP with FOLP and
      reversed by increasing the proportion of enteral nutrition in infants receiving
      FOLP. Replacement of SLP with FOLP in PN-dependent infants who develop PNAC may
      be considered.

PMID- 24576847
TI  - Pack, unpack, bend, twist, pull, push: the physical side of gene expression.
AB  - Molecular motors such as polymerases produce physical constraints on DNA and
      chromatin. Recent techniques, in particular single-molecule micromanipulation,
      provide estimation of the forces and torques at stake. These biophysical
      approaches have improved our understanding of chromatin behaviour under
      physiological physical constraints and should, in conjunction with genome wide
      and in vivo studies, help to build more realistic mechanistic models of
      transcription in the context of chromatin. Here, we wish to provide a brief
      overview of our current knowledge in the field, and emphasize at the same time
      the importance of DNA supercoiling as a major parameter in gene regulation. 

PMID- 24576845
TI  - More novel hantaviruses and diversifying reservoir hosts--time for development of
      reservoir-derived cell culture models?
AB  - Due to novel, improved and high-throughput detection methods, there is a plethora
      of newly identified viruses within the genus Hantavirus. Furthermore, reservoir
      host species are increasingly recognized besides representatives of the order
      Rodentia, now including members of the mammalian orders Soricomorpha/Eulipotyphla
      and Chiroptera. Despite the great interest created by emerging zoonotic viruses,
      there is still a gross lack of in vitro models, which reflect the exclusive host
      adaptation of most zoonotic viruses. The usually narrow host range and genetic
      diversity of hantaviruses make them an exciting candidate for studying virus-host
      interactions on a cellular level. To do so, well-characterized reservoir cell
      lines covering a wide range of bat, insectivore and rodent species are essential.
      Most currently available cell culture models display a heterologous virus-host
      relationship and are therefore only of limited value. Here, we review the
      recently established approaches to generate reservoir-derived cell culture models
      for the in vitro study of virus-host interactions. These successfully used model
      systems almost exclusively originate from bats and bat-borne viruses other than
      hantaviruses. Therefore we propose a parallel approach for research on rodent-
      and insectivore-borne hantaviruses, taking the generation of novel rodent and
      insectivore cell lines from wildlife species into account. These cell lines would
      be also valuable for studies on further rodent-borne viruses, such as orthopox-
      and arenaviruses. 

PMID- 24576848
TI  - Support system for the professional integration of people with disability into
      the labour market.
AB  - BACKGROUND: Successful cases of professional reintegration were achieved when
      adequate conditions were created for the adaptation of the worker with disability
      to the working environment and to the professional activity, allowing them to
      carry out all their functions without any restriction. In this sense, this paper
      presents a methodology for professional integration of people with disability in
      service companies and industry. It has as results a matrix of analysis of a set
      of observables for the reintegration of people with disability into the labour
      market, as well as an auxiliary tool for those who work in recruitment of
      personnel. OBJECTIVE: The main objective was to develop a tool (i.e., a software)
      based on the crossing of data obtained from the analysis of the individual
      capacities and the requirements of the job to optimise the relationship between
      worker and the workplace. There was also considered a series of strategies which
      can be adopted by the individuals and the possible adaptations in the workplace,
      as a way to reduce the handicap in the accomplishment of different activities.
      METHODS: The methodology for the development of this study is divided in two
      phases: Phase I, destined to the assessment criteria and classification of the
      indispensable functional characteristics of the individuals; Phase II, related to
      the assessment criteria of the jobs and the functions that have to be performed.
      RESULTS: As a result it was developed an evaluation tool to match the
      individuals' capabilities and the job requirements. A software was created to
      support the evaluation and to help professionals during the assessment.
      CONCLUSIONS: This methodology together with the support tool demonstrated to be a
      quite inclusive tool, as it considers, as a matter of priority, the capacities of
      the individuals and the real necessities of the workplaces.

PMID- 24576849
TI  - Quantitative high throughput analytics to support polysaccharide production
      process development.
AB  - The rapid development of purification processes for polysaccharide vaccines is
      constrained by a lack of analytical tools current technologies for the
      measurement of polysaccharide recovery and process-related impurity clearance are
      complex, time-consuming, and generally not amenable to high throughput process
      development (HTPD). HTPD is envisioned to be central to the improvement of
      existing polysaccharide manufacturing processes through the identification of
      critical process parameters that potentially impact the quality attributes of the
      vaccine and to the development of de novo processes for clinical candidates,
      across the spectrum of downstream processing. The availability of a fast and
      automated analytics platform will expand the scope, robustness, and evolution of
      Design of Experiment (DOE) studies. This paper details recent advances in
      improving the speed, throughput, and success of in-process analytics at the micro
      scale. Two methods, based on modifications of existing procedures, are described
      for the rapid measurement of polysaccharide titre in microplates without the need
      for heating steps. A simplification of a commercial endotoxin assay is also
      described that features a single measurement at room temperature. These assays,
      along with existing assays for protein and nucleic acids are qualified for
      deployment in the high throughput screening of polysaccharide feedstreams. Assay
      accuracy, precision, robustness, interference, and ease of use are assessed and
      described. In combination, these assays are capable of measuring the product
      concentration and impurity profile of a microplate of 96 samples in less than one
      day. This body of work relies on the evaluation of a combination of commercially
      available and clinically relevant polysaccharides to ensure maximum versatility
      and reactivity of the final assay suite. Together, these advancements reduce
      overall process time by up to 30-fold and significantly reduce sample volume over
      current practices. The assays help build an analytical foundation to support the
      advent of HTPD technology for polysaccharide vaccines. It is envisaged that this
      will lead to an expanded use of Quality by Design (QbD) studies in vaccine
      process development. 

PMID- 24576846
TI  - Modulation of homology-directed repair in T98G glioblastoma cells due to
      interactions between wildtype p53, Rad51 and HCMV IE1-72.
AB  - Human cytomegalovirus (HCMV) is a ubiquitous pathogen capable of causing life
      threatening consequences in neonates and immune-compromised individuals. HCMV
      inflicts site-specific double strand breaks (DSBs) in the cellular genome. DNA
      damage infliction raises the corollary question of virus modulation of DNA
      repair. We recently reported HDR was stimulated in wt human foreskin fibroblasts
      (HFFs) during fully permissive infection or expression of the HCMV protein IE1-72
      (IE72). These studies have been extended into semi-permissive T98G glioblastoma
      cells. T98Gs encode a mutant p53, which may contribute to their high baseline
      rate of HDR. We fully expected HCMV infection to increase HDR in T98Gs, similar
      to its effects in HFFs. Surprisingly in T98Gs HCMV infection, or sole expression
      of IE72, decreased HDR by two-fold. Transient expression of wt p53 in T98Gs also
      reduced HDR by two-fold. Dual transient expression of wt p53 and IE72 restored
      high baseline HDR levels. GST pulldown experiments revealed that both IE72 and wt
      p53 bound the important HDR protein, Rad51. We conclude that the expression of
      certain HCMV proteins can modulate HDR in an infected cell, dependent upon p53
      status. We propose a model of the protein interactions explaining this behavior. 

PMID- 24576850
TI  - Combination therapy for preservation of beta cell function in Type 1 diabetes:
      new attitudes and strategies are needed!
AB  - In several diseases where the immune system plays an important role there has
      been a tremendous progress in treatment efficacy during the last decades. Based
      on necessary basic science these improvements are results of rapid, numerous and
      open-minded clinical trials where pieces of positive results step by step have
      been added into treatment schemes. Treatment of Type 1 diabetes has certainly
      improved but too slowly. It has been difficult to convince the scientific
      community of opinions which among non-professionals have been regarded as common
      sense such as the value of normal blood glucose and preservation of insulin
      secretion. Lack of motivation to participate in clinical trials has slowed down
      progress, as well as too narrow views on both pathogenesis of Type 1 diabetes and
      how studies should be designed to test therapeutic interventions. Studies in
      experimental animals can create and support hypothesis for human conditions but
      must not delay clinical trials too long. There is already evidence enough for
      intervention trials where immune suppression is combined with antigen treatment,
      beta cell protection, anti-inflammatory treatment, and efforts to stimulate beta
      cell regeneration. Regimens should be elaborated and first tried in those groups
      of patients where response can be expected to be best, and thereafter adjusted to
      increase efficacy step-wise, and in broader patient categories. 

PMID- 24576851
TI  - Superconductivity in an electron band just above the Fermi level: possible route
      to BCS-BEC superconductivity.
AB  - Conventional superconductivity follows Bardeen-Cooper-Schrieffer(BCS) theory of
      electrons-pairing in momentum-space, while superfluidity is the Bose-Einstein
      condensation(BEC) of atoms paired in real-space. These properties of solid metals
      and ultra-cold gases, respectively, are connected by the BCS-BEC crossover. Here
      we investigate the band dispersions in FeTe(0.6)Se(0.4)(Tc = 14.5 K ~ 1.2 meV) in
      an accessible range below and above the Fermi level(EF) using ultra-high
      resolution laser angle-resolved photoemission spectroscopy. We uncover an
      electron band lying just 0.7 meV (~8 K) above EF at the Gamma-point, which shows
      a sharp superconducting coherence peak with gap formation below Tc. The estimated
      superconducting gap Delta and Fermi energy [Symbol: see text]F indicate composite
      superconductivity in an iron-based superconductor, consisting of strong-coupling
      BEC in the electron band and weak-coupling BCS-like superconductivity in the hole
      band. The study identifies the possible route to BCS-BEC superconductivity.

PMID- 24576852
TI  - Munchausen syndrome in the act of creating and enacting macroscopic hematuria.

PMID- 24576853
TI  - Optimized lentiviral vectors for HIV gene therapy: multiplexed expression of
      small RNAs and inclusion of MGMT(P140K) drug resistance gene.
AB  - Gene therapy with hematopoietic stem and progenitor cells is a promising approach
      to engineering immunity to human immunodeficiency virus (HIV) that may lead to a
      functional cure for acquired immunodeficiency syndrome (AIDS). In support of this
      approach, we created lentiviral vectors with an engineered polycistronic platform
      derived from the endogenous MCM7 gene to express a diverse set of small antiviral
      RNAs and a drug resistance MGMT(P140K) marker. Multiple strategies for
      simultaneous expression of up to five RNA transgenes were tested. The placement
      and orientation of each transgene and its promoter were important determinants
      for optimal gene expression. Antiviral RNA expression from the MCM7 platform with
      a U1 promoter was sufficient to provide protection from R5-tropic HIV in
      macrophages and resulted in reduced hematopoietic toxicity compared with
      constructs expressing RNA from independent RNA polymerase III promoters. The
      addition of an HIV entry inhibitor and nucleolar TAR RNA decoy did not enhance
      antiviral potency over constructs that targeted only viral RNA transcripts. We
      also demonstrated selective enrichment of gene-modified cells in vivo using a
      humanized mouse model. The use of these less toxic, potent anti-HIV vectors
      expressing a drug selection marker is likely to enhance the in vivo efficacy of
      our stem cell gene therapy approach in treating HIV/AIDS. 

PMID- 24576855
TI  - Twenty-hour growth hormone secretory profiles after aerobic and resistance
      exercise.
AB  - INTRODUCTION: The pulsatile secretion pattern of growth hormone (GH) is an
      important parameter of GH action at peripheral tissues, and more information is
      needed on how exercise impacts GH secretion. This study hypothesized that both
      aerobic and resistance exercise would exhibit dose-response relationships with
      respect to exercise duration and 20-h postexercise GH secretion. METHODS: Eight
      healthy men randomly completed five separate conditions: 1) control (no exercise;
      CON), 2) a moderate-duration (1-h) aerobic exercise session (MA), 3) a long
      duration (2-h) aerobic exercise session (LA), 4) a moderate-duration (1-h)
      resistance exercise session (MR), and 5) a long-duration (2-h) resistance
      exercise session (LR). Exercise intensity, diet, sleep, and physical activity
      were strictly controlled during each condition, and blood was sampled
      postexercise every 20 min for 20 h, and GH secretion parameters were analyzed via
      cluster and deconvolution analyses. RESULTS: Only the 2-h aerobic exercise bout
      resulted in a significant amplification of GH secretion as evidenced by increases
      in GH burst peak amplitude (~100%), basal GH secretion rate (~127%), total GH
      basal secretion (~120%), total pulsatile secretion (~88%), and total GH secretion
      (~89%) over the control (i.e., no exercise) condition. GH secretions for the
      resistance exercise conditions were not different from control. CONCLUSIONS: The
      fact that the 2-h aerobic exercise condition resulted in higher energy
      expenditure than the other exercise conditions could offer a partial explanation
      for the greater GH amplification because of the metabolic effects that GH exerts
      in stimulating postexercise lipolysis. We conclude that extending the duration of
      aerobic exercise, but not resistance exercise, from 1- to 2-h significantly
      amplifies GH secretion during a 20-h period.

PMID- 24576854
TI  - An HIV-encoded antisense long noncoding RNA epigenetically regulates viral
      transcription.
AB  - The abundance of long noncoding RNAs (lncRNAs) and their wide range of functional
      roles in human cells are fast becoming realized. Importantly, lncRNAs have been
      identified as epigenetic modulators and consequently play a pivotal role in the
      regulation of gene expression. A human immunodeficiency virus-encoded antisense
      RNA transcript has recently been reported and we sought to characterize this RNA
      and determine its potential role in viral transcription regulation. The intrinsic
      properties of this human immunodeficiency virus-expressed lncRNA were
      characterized and the data presented here suggest that it functions as an
      epigenetic brake to modulate viral transcription. Suppression of this long
      antisense transcript with small single-stranded antisense RNAs resulted in the
      activation of viral gene expression. This lncRNA was found to localize to the 5'
      long-term repeats (LTR) and to usurp components of endogenous cellular pathways
      that are involved in lncRNA directed epigenetic gene silencing. Collectively, we
      find that this viral expressed antisense lncRNA is involved in modulating human
      immunodeficiency virus gene expression and that this regulatory effect is due to
      an alteration in the epigenetic landscape at the viral promoter. 

PMID- 24576856
TI  - Method for controlled mitochondrial perturbation during phosphorus MRS in
      children.
AB  - Insulin resistance is increasingly prevalent in children and may be related to
      muscle mitochondrial dysfunction, necessitating development of mitochondrial
      assessment techniques. Recent studies used phosphorus magnetic resonance
      spectroscopy (P-MRS), a noninvasive technique appealing for clinical research. P
      MRS requires exercise at a precise percentage of maximum volitional contraction
      (MVC). MVC measurement in children, particularly in those with a disease, is
      problematic because of variability in perception of effort and motivation. We
      therefore developed a method to predict MVC using maximal calf muscle cross
      sectional area (MCSA) to assure controlled and reproducible muscle metabolic
      perturbations. METHODS: Data were collected from 66 sedentary 12- to 20-yr-old
      participants. Plantarflexion MVC was assessed using an MRI-compatible exercise
      treadle device. MCSA of the calf muscles were measured from magnetic resonance
      images. Data from the first 26 participants were used to model the relation
      between MVC and MCSA (predicted MVC = 24.763 + 0.0047 MCSA). This model was then
      applied to the subsequent 40 participants. RESULTS: MVC versus model-predicted
      mean MVC was 43.9 +/- 0.8 kg versus 44.2 +/- 1.81 (P = 0.90). P-MRS results when
      predicted and MVC were similar showed expected changes during MVC-based exercise.
      In contrast, MVC was markedly lower than predicted in four participants and
      produced minimal metabolic perturbation. Upon repeat testing, these individuals
      could perform their predicted MVC with coaching, which produced expected
      metabolic perturbations. CONCLUSIONS: Compared with using MVC testing alone,
      using magnetic resonance imaging to predict muscle strength allows for a more
      accurate and standardized P-MRS protocol during exercise in children. This method
      overcomes a major obstacle in assessing mitochondrial function in youths. These
      studies have importance as we seek to determine the role of mitochondrial
      function in youths with insulin resistance and diabetes and response to
      interventions.

PMID- 24576857
TI  - Effect of N-acetylcysteine on cycling performance after intensified training.
AB  - PURPOSE: This investigation examined the ergogenic effect of short-term oral N
      acetylcysteine (NAC) supplementation and the associated changes in redox balance
      and inflammation during intense training. METHODS: A double-blind randomized
      placebo-controlled crossover design was used to assess 9 d of oral NAC
      supplementation (1200 mg.d) in 10 well-trained triathletes. For each supplement
      trial (NAC and placebo), baseline venous blood and urine samples were taken, and
      a presupplementation cycle ergometer race simulation was performed. After the
      loading period, further samples were collected preexercise, postexercise, and 2
      and 24 h after the postsupplementation cycle ergometer race simulation. Changes
      in total antioxidant capacity, ferric reducing ability of plasma, reduced
      glutathione, oxidized glutathione, thiobarbituric acid-reactive substances,
      interleukin 6, xanthine oxidase, hypoxanthine, monocyte chemotactic protein 1,
      nuclear factor kappaB, and urinary 15-isoprostane F2t concentration were
      assessed. The experimental procedure was repeated with the remaining supplement
      after a 3-wk washout. Eight participants completed both supplementation trials.
      RESULTS: NAC improved sprint performance during the cycle ergometer race
      simulation (P < 0.001, etap = 0.03). Supplementation with NAC also augmented
      postexercise plasma total antioxidant capacity (P = 0.005, etap = 0.19), reduced
      exercise-induced oxidative damage (plasma thiobarbituric acid-reactive
      substances, P = 0.002, etap = 0.22; urinary 15-isoprostane F2t concentration, P =
      0.010, etap = 0.431), attenuated inflammation (plasma interleukin 6, P = 0.002,
      etap = 0.22; monocyte chemotactic protein 1, P = 0.012, etap = 0.17), and
      increased postexercise nuclear factor kappaB activity (P < 0.001, etap = 0.21).
      CONCLUSION: Oral NAC supplementation improved cycling performance via an improved
      redox balance and promoted adaptive processes in well-trained athletes undergoing
      strenuous physical training.

PMID- 24576858
TI  - Effects of altered airway function on exercise ventilation in asthmatic adults.
AB  - PURPOSE: Variable airway function is a central feature of the asthmatic
      condition. Thus, habitually active asthmatics are certain to exercise under
      conditions of variable airway (dys)function. The purpose of this study was to
      determine the effects of variable preexercise airway function on ventilation
      during whole-body exercise in asthmatic adults. METHODS: Eight mild asthmatic
      (age = 26 yr; VO2peak = 49 mL.kg.min) and nine nonasthmatic (age = 30 yr; VO2peak
      = 46 mL.kg.min) adults performed constant workrate cycling exercise to exhaustion
      after four separate interventions: 1) a control trial (CON); 2) inhalation of
      fast-acting beta2-agonist (BD); 3) eucapnic voluntary hyperpnea challenge (BC);
      and 4) sham to the hyperpnea (SHAM). Pulmonary function was assessed at baseline
      and after each intervention. Exercise ventilation and operating lung volumes were
      compared among the four exercise trials in both control and asthmatic subjects.
      RESULTS: Baseline pulmonary function was significantly lower in asthmatic
      subjects compared with control subjects. In asthmatic subjects, postintervention
      (i.e., preexercise) forced expiratory volume 1.0 s was significantly different
      among the four exercise trials (CON = 3.5 +/- 0.4, BD = 4.1 +/- 0.4, SHAM = 3.6
      +/- 0.3, BC = 2.8 +/- 0.3 L, P < 0.05), whereas it was not different in control
      subjects. There were no differences in exercise ventilation or operating lung
      volumes during exercise among the four trials either within asthmatic subjects or
      between control and asthmatic subjects. CONCLUSIONS: These findings suggest that
      the state of airway function-whether bronchodilated or bronchoconstricted-before
      exercise in the mild asthmatic does not affect the exercise ventilatory response.
      Thus, ventilatory system function in the asthmatic appears to be responsive to
      the acute requirement for increased airflow during whole-body exercise.

PMID- 24576859
TI  - Postprandial plasma incretin hormones in exercise-trained versus untrained
      subjects.
AB  - INTRODUCTION: After food ingestion, the incretin hormones, glucagon-like peptide
      1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), are secreted by
      the intestines into circulation where they act on the pancreas to promote insulin
      secretion. We evaluated the hypothesis that low postprandial plasma insulin
      levels in lean exercise-trained individuals are associated with low
      concentrations of incretin hormones. METHODS: A cross-sectional study was
      performed to compare postprandial incretin hormone levels in lean endurance
      exercise-trained individuals (EX; n = 14, >=40 yr) and age- and sex-matched,
      nonobese, sedentary control subjects (CON, n = 14). The main outcome measures
      were GLP-1, GIP, insulin, and glucose incremental areas under the curve (AUC) as
      measured in plasma samples collected during a 2-h,75-g oral glucose tolerance
      test (OGTT). RESULTS: The EX group had lower body fat percentage (14.6% +/- 1.1%
      vs 23.3% +/- 1.7%, P = 0.0002) and higher maximal oxygen uptake (53 +/- 2 vs 34
      +/- 2, P < 0.0001) than CON. Glucose AUC did not differ between groups (P =
      0.20). Insulin AUC was lower in EX (2.5 +/- 0.5 vs 4.2 +/- 1.2 MUU.mL.1000 min, P
      = 0.02). No differences were observed between groups (EX and CON, respectively)
      for GLP-1 AUC (3.5 +/- 0.7 vs 4.1 +/- 1.1 pmol.min.100 L, P = 0.61) or GIP AUC
      (19.2 +/- 1.4 vs 18.0 +/- 1.4 pg.min.1000 mL; P = 0.56). In CON, insulin AUC was
      correlated with AUC for GLP-1 (r = 0.53, P = 0.05) and GIP (r = 0.71, P = 0.004),
      but no such correlations were observed in EX (both P >= 0.67). CONCLUSIONS: Low
      postprandial insulin levels in lean exercise-trained individuals are not
      attributable to lower incretin hormone concentrations. However, exercise may
      decrease the dependency of postprandial insulin levels on incretin hormones.

PMID- 24576860
TI  - Ethnic differences in physical activity and metabolic risk: the Dallas Heart
      Study.
AB  - PURPOSE: This study aimed to examine ethnic differences in objectively measured
      physical activity (PA) and the relationship between PA and metabolic risk
      factors. METHODS: The analysis included 2566 participants of the Dallas Heart
      Study (53% non-Hispanic black, 32% non-Hispanic white, and 15% Hispanic) who wore
      an accelerometer for an average of 7 d. PA was assessed as mean activity counts
      and time spent in moderate and vigorous activity. Outcomes included body mass
      index (BMI), waist circumference, systolic and diastolic blood pressure, heart
      rate, fasting glucose, homeostatic model assessment of insulin resistance, and
      plasma lipid and lipoprotein levels. RESULTS: A higher proportion of Hispanics
      than either whites or blacks obtained the recommended >= 150 min.wk of moderate
      PA (24%, 14%, and 10%, respectively, P < 0.0001). White males were more likely to
      engage in vigorous activity than other sex-ethnic groups (P < 0.05). Time in
      moderate-to-vigorous activity was inversely related to BMI, waist circumference,
      homeostatic model assessment of insulin resistance, heart rate, and positively
      associated with high-density lipoprotein cholesterol levels (P < 0.0001) in the
      combined cohort, and the relationship was similar in all ethnic groups (P
      interaction > 0.05). A significant inverse association between PA and
      triglycerides was observed in whites (P = 7.2 * 10). Vigorous activity was
      associated with greater differences in risk factors than moderate activity (for
      example, beta = -0.30 vs beta = -0.02 for BMI). Bouts lasting >=10 min were
      associated with metabolic risk factors independent of <10-min bouts in the
      overall sample, with similar trends observed within subgroups. CONCLUSIONS:
      Hispanics had higher levels of moderate activity than whites or blacks, whereas
      white men had higher levels of vigorous PA than other sex-ethnic groups. The
      relationship between PA and several metabolic risk factors was similar across
      ethnicities. Vigorous PA was associated with greater benefits than moderate PA.

PMID- 24576861
TI  - Evaluation of anthropometric equations to assess body fat in adults: NHANES 1999
      2004.
AB  - PURPOSE: Equations that estimate percentage body fat (PBF) from anthropometrics
      are widely used, although most were developed in small nonrepresentative samples.
      No study has examined the generalizability of these equations in a nationally
      representative population. This study evaluated the validity of 26 sets (2 for
      males and 3 for females only) of published equations for PBF estimation in
      American adults using data from the National Health and Nutrition Examination
      Survey 1999-2004. METHODS: Data were from 9934 adults ages >=20 yr. Stratified by
      sex, equations were evaluated against dual-energy x-ray absorptiometry using R,
      root mean square error, and mean signed difference. Differential bias was
      evaluated by the absolute value of the discrepancy between the mean signed
      difference values in normal weight and obese adults. RESULTS: In subgroups
      matched to the range of age and race/ethnicity in which equations were derived,
      most equations had R values between 0.5 and 0.7 and root mean square error
      estimates between 3.0 and 4.0 percentage points for males and between 3.5 and 4.5
      percentage points for females. Analyses in sample stratified by age, obesity
      status, or race/ethnicity showed that 15 of the 23 equations for males and 20 of
      the 24 equations for females had important differential bias of more than two
      percentage points. Equations that included WC performed the best in males, and
      those that included body mass index performed best in females. Equations using
      skinfold thickness performed less well in older adults. CONCLUSIONS: Published
      PBF equations had moderately strong R values in a representative sample of
      American men and women, but both nondifferential and differential biases were
      substantial for most equations.

PMID- 24576862
TI  - Tracking career performance of successful triathletes.
AB  - PURPOSE: Tracking athletes' performances over time is important but problematic
      for sports with large environmental effects. Here we have developed career
      performance trajectories for elite triathletes, investigating changes in swim,
      cycle, run stages, and total performance times while accounting for environmental
      and other external factors. METHODS: Performance times of 337 female and 427 male
      triathletes competing in 419 international races between 2000 and 2012 were
      obtained from triathlon.org. Athletes were categorized according to any top 16
      placing at World Championships or Olympics between 2008 and 2012. A mixed linear
      model accounting for race distance (sprint and Olympic), level of competition,
      calendar-year trend, athlete's category, and clustering of times within athletes
      and races was used to derive athletes' individual quadratic performance
      trajectories. These trajectories provided estimates of age of peak performance
      and predictions for the 2012 London Olympic Games. RESULTS: By markedly reducing
      the scatter of individual race times, the model produced well-fitting
      trajectories suitable for comparison of triathletes. Trajectories for top 16
      triathletes showed different patterns for race stages and differed more among
      women than among men, but ages of peak total performance were similar for men and
      women (28 +/- 3 yr, mean +/- SD). Correlations between observed and predicted
      placings at Olympics were slightly higher than those provided by placings in
      races before the Olympics. CONCLUSIONS: Athletes' trajectories will help identify
      talented athletes and their weakest and strongest stages. The wider range of
      trajectories among women should be taken into account when setting talent
      identification criteria. Trajectories offer a small advantage over usual race
      placings for predicting men's performance. Further refinements, such as
      accounting for individual responses to race conditions, may improve utility of
      performance trajectories.

PMID- 24576863
TI  - A simple nonexercise model of cardiorespiratory fitness predicts long-term
      mortality.
AB  - PURPOSE: Cardiorespiratory fitness (CRF) is a strong predictor of future health,
      but measurements of CRF are time consuming and involve costly test procedures. We
      assessed whether a simple, non-exercise-based test of CRF predicted long-term all
      cause and cardiovascular disease (CVD) mortality. METHODS: In this prospective
      cohort study, we used a previously published nonexercise test to estimate CRF in
      healthy men (n = 18,348) and women (n = 18,764) from the first HUNT study (1984
      1986) in Norway. We used Cox regression to obtain HR for mortality during a mean
      follow-up of 24 yr. Assessment of model validity was performed by standard
      procedures of discrimination and calibration. RESULTS: CRF was inversely
      associated with all-cause and CVD mortality in men and women below 60 yr of age
      at baseline, after adjustment for confounders. For each MET-higher CRF (MET,
      approximately 3.5 mL.kg.min), HR for CVD mortality was 21% lower in both men (95%
      confidence interval (CI), 17%-26%) and women (95% CI, 12%-29%). HR for all-cause
      mortality was 15% (95% CI, 12%-17%) lower in men and 8% (95% CI, 3%-3%) lower in
      women for each MET-higher CRF. The ability of the model to discriminate mortality
      risk among participants below 60 yr was better for CRF (area under the curve
      (AUC), 0.70-0.77) compared with that for each variable that constituted the model
      (AUC, 0.55-0.63) and an aggregated sum of z-scores for each variable (AUC, 0.61
      0.65). Comparison of observed and predicted risk indicated good model
      calibration. CONCLUSIONS: This method of assessing CRF is feasible and
      practically useful in primary care for identification of apparently healthy
      individuals at increased risk of premature CVD disease and all-cause mortality.

PMID- 24576864
TI  - Creatine supplementation during resistance training in older adults-a meta
      analysis.
AB  - INTRODUCTION: Age-related sarcopenia and dynapenia have negative effects on
      strength and the ability to perform activities of daily living. Resistance
      training (RT) increases muscle mass and strength in older adults and is an
      established countermeasure for sarcopenia and dynapenia, and creatine may enhance
      this effect. We aimed to determine whether the addition of Cr to RT increased
      gains in muscle mass, strength, and function in older adults over RT alone by
      conducting a systematic review and meta-analysis. METHODS: PubMed and Healthstar
      databases were searched. Randomized, placebo-controlled trials that involved
      older adults supplemented with Cr and included RT regimens (>6 wk) were included.
      Data were analyzed using fixed or random (if data were heterogeneous) effects
      meta-analysis using RevMan 5. RESULTS: The meta-analysis comprised 357 older
      adults (average +/- SD Cr: 63.6 +/- 5.9 yr, Pl: 64.2 +/- 5.4 yr) with 12.6 +/-
      4.9 wk of RT. Cr + RT increased total body mass (P = 0.004) and fat-free mass (P
      < 0.0001) with no effect on fat mass as compared with RT alone. Cr + RT increased
      chest press (P = 0.004) and leg press (P = 0.02) one-repetition maximum to a
      greater extent than RT alone, with no difference in the effect on knee extension
      or biceps curl one-repetition maximum, isokinetic or isometric knee extension
      peak torque. Cr + RT had a greater effect than RT alone on the 30-s chair stand
      test (P = 0.03). CONCLUSION: Retention of muscle mass and strength is integral to
      healthy aging. The results from this meta-analysis are encouraging in supporting
      a role for Cr supplementation during RT in healthful aging by enhancing muscle
      mass gain, strength, and functional performance over RT alone; however, the
      limited number of studies indicates further work is needed.

PMID- 24576865
TI  - Exercise before scuba diving ameliorates decompression-induced neutrophil
      activation.
AB  - INTRODUCTION: The goals of this study were to investigate the difference in
      responses between a scuba dive preceded by aerobic exercise (EX) and a
      nonexercise control dive (CON) and to further evaluate the potential relation
      between venous gas emboli (VGE) and microparticles (MP). We hypothesized that
      exercise would alter the quantity and subtype of annexin V-positive MP and VGE.
      METHODS: Nineteen divers performed two dives to 18 m seawater for 41 min
      separated by at least 3 d, one of which was preceded by 60 min of treadmill
      interval exercise. Blood was obtained before exercise, before diving, and 15 min,
      2 h, 4 h, and 24 h after surfacing. Intravascular bubbles were quantified by
      transthoracic echocardiography at 15, 40, 80, and 120 min. RESULTS: The median
      VGE remained unchanged between the two dives; however, there was a significant
      increase in VGE in the exercise dive at 40 and 80 min at rest. MP were
      significantly elevated by approximately 2 times at all time points after CON
      compared with those after EX. Markers of neutrophil and platelet activation were
      elevated by both dives, and these elevations were attenuated in the EX dive.
      CONCLUSIONS: We conclude that some of the differences observed between the EX and
      CON related to MP and platelet and neutrophil activation provide additional
      insight into the potential protective benefits of exercise; however, further
      study is needed to understand the mechanism and true potential of these benefits.

PMID- 24576867
TI  - Self-esteem mediates associations of physical activity with anxiety in college
      women.
AB  - PURPOSE: Why physically active people report lower anxiety than those who are
      inactive is not well understood. This study examined whether physical self
      concept and self-esteem would mediate associations of self-reported physical
      activity with anxiety disorder symptoms in young women, a population with
      elevated risk for developing an anxiety disorder. METHODS: College women (N =
      1036, mean +/- SD = 19.7 +/- 2.9 yr) completed a physical activity recall, the
      Psychiatric Diagnostic Screening Questionnaire, and the Physical Self-Description
      Questionnaire. Structural equation modeling was used to test hypotheses. RESULTS:
      Physical activity had inverse, indirect associations with symptoms of social
      phobia, generalized anxiety disorder, and obsessive-compulsive disorder that were
      expressed through its positive association with specific and global physical self
      concept and self-esteem. The results were independent of similar relations with
      symptoms of major depressive disorder as well as the estimates of body fatness
      and use of psychotropic medications. CONCLUSIONS: These correlational findings
      provide initial evidence to warrant experimental efficacy trials of whether
      physical activity will reduce the risk of anxiety disorders in young women by
      positive influences on physical self-concept and self-esteem.

PMID- 24576866
TI  - Calcium supplementation and parathyroid hormone response to vigorous walking in
      postmenopausal women.
AB  - INTRODUCTION: Disruptions in calcium (Ca) homeostasis during exercise may
      influence skeletal adaptations to exercise training. In young men, vigorous
      cycling causes increases in parathyroid hormone (PTH) and bone resorption (C
      terminal telopeptides of type I collagen [CTX]); responses are attenuated by Ca
      supplementation. The study aimed to determine whether vigorous walking causes
      similar increases in PTH and CTX in older women and how the timing of Ca
      supplementation before and during exercise influences these responses. METHODS:
      In experiment 1, 10 women (61 +/- 4 yr) consumed 125 mL of either a Ca-fortified
      (1 g.L) or control beverage every 15 min during exercise starting 60 min before
      and continuing during 60 min of exercise. In experiment 2, 23 women (61 +/- 4 yr)
      consumed 200 mL of a Ca-fortified (1 g.L) or control beverage every 15 min
      starting 15 min before and continuing during 60 min of exercise. The exercise was
      treadmill walking at 75%-80% VO2peak. RESULTS: In experiment 1, serum ionized Ca
      decreased in the control condition (P < 0.001), but not with Ca supplementation.
      PTH increased after exercise on both days (Ca, P = 0.05; control, P = 0.009) but
      was attenuated by Ca supplementation (8.3 vs 26.1 pg.mL; P = 0.03). CTX increased
      only on the control day (P = 0.02). In experiment 2, serum ionized Ca decreased
      on Ca and control days (Ca and control, P < 0.001), but less so on the Ca day (P
      = 0.04). PTH (Ca and control, P < 0.001) and CTX (Ca, P = 0.02; control P =
      0.007) increased on the Ca and control day, and there were no differences in the
      changes. CONCLUSION: The timing of Ca supplementation may be a key mediator of Ca
      homeostasis during acute exercise. Further research is necessary to determine how
      this influences skeletal adaptations to training.

PMID- 24576868
TI  - Effects of moderate- and intermittent low-intensity exercise on postprandial
      lipemia.
AB  - The elevation of postprandial plasma triglycerides (PPTG) in the blood is an
      independent risk factor for atherosclerosis. Although acute exercise typically
      attenuates PPTG, the effect of exercise intensity on PPTG is less well
      established, particularly in well-controlled conditions for physical activities
      and diet. PURPOSE: We sought to determine the efficacy of exercise at 65% VO2max
      with an extended sitting time and isoenergetic intermittent walking exercise at a
      self-selected walking speed (approximately 25% VO2max) on PPTG compared with that
      of a sitting control condition. In a randomized crossover design, nine healthy
      young men completed three trials with a >1-wk interval between trials. After 2 d
      of activity and diet normalization, participants performed prolonged sitting
      nonexercise control (CON), prolonged sitting with subsequent 1-h running at 65%
      VO2max (MOD), or isoenergetic intermittent walking at approximately 25% VO2max
      (LOW) on day 3. This was followed on day 4 by a 6-h high-fat tolerance test.
      RESULTS: MOD and LOW reduced incremental triglyceride (TG) area under the curve
      (TG AUCI) compared with that in CON by 33.6% (P < 0.005) and 19.8% (P < 0.05),
      respectively. MOD also reduced TG AUCI compared with that in LOW by 17.2% (P <
      0.03). The reduced TG AUCI in MOD was accompanied by reduced plasma glucose
      response and enhanced fat oxidation compared with those in LOW and CON (for all,
      P < 0.05), respectively. CONCLUSIONS: Both MOD and LOW were effective in reducing
      PPTG compared with CON. However, MOD was more effective in reducing PPTG compared
      with LOW.

PMID- 24576869
TI  - Highly strong and elastic graphene fibres prepared from universal graphene oxide
      precursors.
AB  - Graphene fibres are continuously prepared from universal graphene oxide
      precursors by a novel hydrogel-assisted spinning method. With assistance of a
      rolling process, meters of ribbon-like GFs, or GRs with improved conductivity,
      tensile strength, and a long-range ordered compact layer structure are
      successfully obtained. Furthermore, we refined our spinning process to obtained
      elastic GRs with a mixing microstructure and exceptional elasticity, which may
      provide a platform for electronic skins and wearable electronics, sensors, and
      energy devices. 

PMID- 24576870
TI  - More than at the neuromuscular synapse: actions of botulinum neurotoxin A in the
      central nervous system.
AB  - Botulinum neurotoxin type A (BoNT/A) is a metalloprotease that produces a
      sustained yet transitory blockade of transmitter release from peripheral nerve
      terminals. Local delivery of this neurotoxin is successfully employed in clinical
      practice to reduce muscle hyperactivity such as in spasticity and dystonia, and
      to relieve pain with long-lasting therapeutic effects. However, not all BoNT/A
      effects can be explained by an action at peripheral nerve terminals. Indeed, it
      appears that BoNT/A is endowed with trafficking properties similar to the
      parental tetanus neurotoxin and thus be able to directly affect the CNS. In this
      review, we present and discuss novel compelling evidence for a direct central
      effect of BoNT/A in both dorsal and ventral horns of the animal and human spinal
      cord after peripheral injection of the neurotoxin, with important consequences on
      pain and motor control. This new knowledge is expected to radically change the
      approach to the use of BoNT/A in the future. As BoNT/A central action appears to
      also contribute to functional improvement, for instance in human spastic gait,
      the challenge will be to develop new subtypes or BoNT derivatives with
      deliberate, cell-specific central effects in order to fully exploit the spectrum
      of BoNT/A therapeutic activity. 

PMID- 24576871
TI  - Expression of cholecystokinin, gastrin, and their receptors in the mouse cornea.
AB  - PURPOSE: Cholecystokinin (CCK) is a neuropeptide that has been identified in
      trigeminal ganglion neurons. Gastrin (GAST) is a related peptide never explored
      in the cornea. The presence and role of both gastrointestinal peptides in the
      cornea and corneal sensory neurons remain to be established. We explored here in
      mice whether CCK, GAST, and their receptors CCK1R and CCK2R are expressed in the
      corneal epithelium and trigeminal ganglion neurons innervating the cornea.
      METHODS: We used RT-PCR analysis to detect mRNAs of CCK, GAST, CCK1R, and CCK2R
      in mouse cornea epithelium, trigeminal ganglia, and primary cultured corneal
      epithelial cells. Immunofluorescence microscopy was used to localize these
      peptides and their receptors in the cornea, cultured corneal epithelial cells,
      and corneal nerves, as well as in the cell bodies of corneal trigeminal ganglion
      neurons identified by retrograde labeling with Fast Blue. RESULTS: Mouse corneal
      epithelial cells in the cornea in situ and in cell cultures expressed CCK and
      GAST. Only the receptor CCK2R was found in the corneal epithelium. In addition,
      mouse corneal afferent sensory neurons expressed CCK and GAST, and the CCK1R
      receptors. CONCLUSIONS: The presence of CCK, GAST, and their receptors in the
      mouse corneal epithelium, and in trigeminal ganglion neurons supplying sensory
      innervation to the cornea, opens the possibility that these neuropeptides are
      involved in corneal neurogenic inflammation and in the modulation of
      repairing/remodeling processes following corneal injury.

PMID- 24576872
TI  - Three-dimensional optical coherence tomography evaluation of vascular changes at
      arteriovenous crossings.
AB  - PURPOSE: To study the three-dimensional morphologic features of retinal
      arteriovenous crossings with optical coherence tomography (OCT) and elucidate the
      vascular changes associated with crossing phenomena as seen on fundus
      photographs. METHODS: We examined 150 consecutive eyes with no ocular disease. In
      each eye, fundus photographs were taken, and one randomly selected arteriovenous
      crossing was examined by OCT. The OCT analysis was performed by using sequential
      thin sections along and perpendicular to the retinal vessels. RESULTS: The OCT
      analysis of these arteriovenous crossings showed that the veins abruptly changed
      their directions to pass the artery and frequently displayed focal luminal
      narrowing with no compression or flattening. The OCT measurements revealed that
      the veins narrowed by 21.0% +/- 12.9% at the crossings. The degree of narrowing
      correlated positively with the diameter of the crossing arteries (r = 0.419, P <
      0.001). On fundus photographs, crossing phenomena were observed in 103 of the 150
      selected crossings. Venous narrowing measured by OCT was more severe in eyes with
      crossing phenomena on fundus photographs (P < 0.001). Four types of crossing
      phenomena were observed: concealment, tapering, deflection, and humping. Venous
      narrowing rates were similar among all four types. Although the subjects with
      deflection or humping phenomena were more likely to suffer from hypertension, the
      mean venous narrowing rate at such crossings was similar to that observed with
      the other crossing phenomena. CONCLUSIONS: Arteriovenous crossings exhibited
      focal narrowing of the venous lumen with no compression or flattening. Increased
      venous narrowing and larger arteries were observed at crossings with crossing
      phenomena.

PMID- 24576874
TI  - Retinal hemodynamic effects of antioxidant supplementation in an endotoxin
      induced model of oxidative stress in humans.
AB  - PURPOSE: The Age-Related Eye Disease Study 1 (AREDS 1) has shown that nutritional
      supplementation with antioxidants and zinc modifies the natural course of AMD. It
      is presumed that the supplements exert their beneficial effects by ameliorating
      oxidative stress due to the scavenging of reactive oxygen species (ROS). We have
      shown in a human model that under oxidative stress induced by administration of
      lipopolysaccharide (LPS) the vasoconstrictor response of retinal vessels to
      oxygen breathing is diminished. This reduced vascular response to hyperoxia was
      previously shown to be normalized by the AREDS 1 supplements. In the present
      study, we tested the hypothesis that the response can also be restored by a
      different antioxidant formulation. METHODS: This randomized, double-masked,
      placebo-controlled parallel group study included 40 healthy volunteers. On each
      study day, retinal red blood cell (RBC) flow and the reactivity of retinal RBC
      flow to hyperoxia were investigated in the absence and presence of 2 ng/kg LPS.
      Between the two study days, subjects received either the supplement or placebo
      for 14 days. RESULTS: Before supplementation LPS reduced retinal arterial
      vasoconstriction (P < 0.001) and reactivity of retinal RBC flow (P = 0.03) in
      response to 100% oxygen breathing. Two weeks of supplementation did not affect
      baseline retinal RBC flow, but normalized the LPS-induced change in the response
      to hyperoxia. The arterial vasoconstrictor response during LPS and 100% oxygen
      breathing was 4.1 +/- 1.0% after administration of placebo and 10.6 +/- 0.9%
      after supplementation (P = 0.005). The response of RBC flow to 100% oxygen
      breathing during LPS was 52.2 +/- 2.1% after administration of placebo and 59.5
      +/- 2.0% after supplementation (P = 0.033). CONCLUSIONS: Our data show that the
      supplement used in the present study can normalize the response of retinal RBC
      flow to hyperoxia under LPS administration. This indicates that supplementation
      can prevent endothelial dysfunction induced by oxidative stress, which is assumed
      to play a role in the pathophysiology of AMD. (ClinicalTrials.gov number,
      NCT00914576.).

PMID- 24576875
TI  - The effects of monochromatic illumination on early eye development in rhesus
      monkeys.
AB  - PURPOSE: Influence of longitudinal chromatic aberration (LCA) on emmetropization
      during early eye development has not been studied in primates. We investigated
      the effects of quasi-monochromatic lighting on refractive development and eye
      growth in rhesus monkeys. METHODS: Infant rhesus monkeys were raised under one of
      three lighting conditions for 51 weeks: quasi-monochromatic blue light (peak 455
      nm), red light (peak 610 nm), and white light (color temperature 5000 K). All
      animals underwent biometric measurements using cycloplegic streak retinoscope,
      keratometry, and A-scan ultrasonography for refraction, corneal power, and axial
      components, respectively, at designated time points. RESULTS: At the 51st week,
      the mean difference in refraction of the white light and blue light groups,
      compared with that of the red light group, reached 1.71 diopters (D) and 1.43 D,
      respectively (both P < 0.001). Two monkeys in the red light group developed
      myopia at the 16th week, whereas the other seven remained hyperopic throughout
      the experiment. No significant difference in mean refraction was observed between
      the blue light group and white light group. CONCLUSIONS: Illumination from long
      wavelength light during early life could be a risk factor for the development of
      myopia in a small proportion of rhesus monkeys that are sensitive to L-cone
      stimulation.

PMID- 24576873
TI  - Light damage in Abca4 and Rpe65rd12 mice.
AB  - PURPOSE: Bisretinoids form in photoreceptor cells and accumulate in retinal
      pigment epithelium (RPE) as lipofuscin. To examine the role of these fluorophores
      as mediators of retinal light damage, we studied the propensity for light damage
      in mutant mice having elevated lipofuscin due to deficiency in the ATP-binding
      cassette (ABC) transporter Abca4 (Abca4(-/-) mice) and in mice devoid of
      lipofuscin owing to absence of Rpe65 (Rpe65(rd12)). METHODS: Abca4(-/-),
      Rpe65(rd12), and wild-type mice were exposed to 430-nm light to produce a
      localized lesion in the superior hemisphere of retina. Bisretinoids of RPE
      lipofuscin were measured by HPLC. In histologic sections, outer nuclear layer
      (ONL) thickness was measured as an indicator of photoreceptor cell degeneration,
      and RPE nuclei were counted. RESULTS: As shown previously, A2E levels were
      increased in Abca4(-/-) mice. These mice also sustained light damage-associated
      ONL thinning that was more pronounced than in age-matched wild-type mice; the ONL
      thinning was also greater in 5-month versus 2-month-old mice. Numbers of RPE
      nuclei were reduced in light-stressed mice, with the reduction being greater in
      the Abca4(-/-) than wild-type mice. In Rpe65(rd12) mice bisretinoid compounds of
      RPE lipofuscin were not detected chromatographically and light damage-associated
      ONL thinning was not observed. CONCLUSIONS: Abca4(-/-) mice that accumulate RPE
      lipofuscin at increased levels were more susceptible to retinal light damage than
      wild-type mice. This finding, together with results showing that Rpe65(rd12) mice
      did not accumulate lipofuscin and did not sustain retinal light damage, indicates
      that the bisretinoids of retinal lipofuscin are contributors to retinal light
      damage.

PMID- 24576876
TI  - Pattern electroretinograms during the cold pressor test in normals and glaucoma
      patients.
AB  - PURPOSE: To examine the influence of the cold pressor test (CPT) on steady-state
      pattern electroretinograms (PERG) in healthy subjects and glaucoma patients.
      METHODS: Steady-state PERGs to 7.8 Hz pattern reversal stimuli were recorded in
      63 subjects. Fifteen healthy control subjects, 14 patients with ocular
      hypertension (OHT), and 34 patients with open-angle glaucoma (20 normotensive
      [NTG] and 14 high tension glaucoma [HTG]) were examined. Steady-state PERG
      amplitudes and latencies were analyzed at baseline, during cold stimulus using a
      modified CPT, and during the subsequent recovery phase. Blood pressure and heart
      rate were simultaneously recorded in 10 normals and 11 glaucoma patients.
      RESULTS: During the three test conditions (baseline, ice water, and warm water)
      glaucoma patients (NTG and HTG) showed significantly reduced PERG amplitudes in
      comparison with control subjects (P < 0.001) and with OHT patients (P < 0.004).
      Patients with OHT displayed lower PERG amplitudes than control subjects
      (nonsignificant, with consideration of Bonferroni). Only NTG patients showed a
      significant effect of the CPT on PERG amplitude (significant decrease during warm
      water P = 0.02). Latencies shortened significantly during warm-water period after
      cold stimulus in control subjects (P = 0.05) and in NTG patients (P = 0.02) with
      a nonsignificant trend of shortened latencies in the OHT (P = 0.06) and HTG
      groups (P = 0.3). Systolic and diastolic blood pressure increased during cold
      water (P < 0.001) and decreased during warming-up conditions (P < 0.001).
      CONCLUSIONS: This study shows that a CPT influences the PERG responses
      particularly in NTG. (ClinicalTrials.gov number, NCT00494923.).

PMID- 24576877
TI  - Topographic profiles of retinal nerve fiber layer defects affect the diagnostic
      performance of macular scans in preperimetric glaucoma.
AB  - PURPOSE: To evaluate the influence of topographic profiles (i.e., inner
      directional angle and angular width) of localized retinal nerve fiber layer
      (RNFL) defects on the diagnostic performance of macular ganglion cell-inner
      plexiform layer (GCIPL) thickness in discriminating preperimetric glaucoma (PPG)
      eyes from normal control eyes. METHODS: The ganglion cell analysis algorithm in
      Cirrus OCT was performed to determine the macular GCIPL thickness. Areas under
      the receiver operating characteristic curves (AUROCs) and the
      sensitivities/specificities based on an internal normative database were
      evaluated. The effect of the inner directional angle and the angular width of
      localized RNFL defects on the diagnostic performance of macular GCIPL parameters
      were evaluated by using linear-by-linear association analysis and logistic
      regression analysis. RESULTS: Ninety-two patients with PPG and 92 age-matched
      healthy control subjects were enrolled in this study. The AUROC of the best
      parameters in macular GCIPL was 0.823 (inferotemporal sector), which showed no
      significant difference in comparison to the best parameters of peripapillary RNFL
      (7 o'clock sector, 0.764) and optic nerve head (rim area, 0.767) (for all
      comparisons, P > 0.05). A significant linear association was observed between the
      inner directional angle of RNFL defects and the sensitivity of macular GCIPL
      parameters for detecting RNFL defects. The angular width of RNFL defects was not
      significantly associated with the sensitivity of macular GCIPL parameters.
      CONCLUSIONS: The diagnostic ability of macular GCIPL parameters was comparable to
      that of peripapillary RNFL and ONH parameters in PPG. The inner directional angle
      of RNFL defects, but not the angular width, affects the diagnostic sensitivity of
      macular GCIPL parameters.

PMID- 24576878
TI  - Comparison of two methods to measure macular pigment optical density in healthy
      subjects.
AB  - PURPOSE: To evaluate and compare macular pigment optical density (MPOD)
      measurements obtained using the modified Heidelberg Retina Angiograph (HRA) and
      the Visucam 200. METHODS: Healthy young subjects were included in this
      prospective study. MPOD was measured with the modified HRA at 0 degrees  and 0.5
      degrees , 1 degrees , 2 degrees , and 6 degrees  eccentricities from the fovea.
      The parameters obtained with the Visucam 200 (maximum, mean, area, and volume)
      were recorded the same day on the same subjects. Intraclass correlation
      coefficients (ICCs) and correlation coefficients were used to evaluate the
      agreement between the two devices. The repeatability and the reproducibility of
      each method were also assessed. RESULTS: Sixty-seven subjects were included whose
      median (interquartile ratio) age was 25 years (range, 23-30 years). The MPODs as
      measured with the modified HRA were higher than those measured with the Visucam
      200 (P < 0.0001). The ICCs were low, ranging from 0.020 to 0.188. The correlation
      coefficients between the two methods were very low and ranged from 0.05 to 0.22.
      Repeatability and reproducibility were good with both methods, with ICCs ranging
      from 0.697 to 0.923. CONCLUSIONS: Agreement between the modified HRA and the
      Visucam in measuring MPOD was rather low. These results suggest that the two
      methods are not interchangeable. Before using the Visucam 200 in clinical and
      research setting, further evaluation seems mandatory (http://ansm.sante.fr/
      number, 2009-A00448-49).

PMID- 24576879
TI  - Cell senescence reduced the mechanotransduction sensitivity of porcine angular
      aqueous plexus cells to elevation of pressure.
AB  - PURPOSE: To investigate the effect of pressure/flow on the barrier function and
      protein expression of normal and senescent porcine aqueous humor plexus (AAP)
      cells, which are the porcine equivalent of human Schlemm's canal endothelial
      cells. METHODS: AAP cells were grown for 2 weeks in physiological (5% O2) or
      hyperoxic conditions (40% O2) to model cell senescence. Control and senescent AAP
      cells were subjected to control and elevated hydrostatic pressure gradient of 10
      mm Hg for 72 hours. Hydraulic conductivity (HC) and transendothelial electric
      resistance (TEER) were measured. The expressions of senescence-associated beta
      galactosidase and DNA damage marker 8-hydroxy-2'-deoxyguanosine (8-OHdG) were
      monitored, and the protein expression profile was analyzed by Western blot.
      RESULTS: After 14 days of hyperoxia, AAP cells stained positive for 8-OHdG and
      beta-galactosidase. Pressure elevation/flow resulted in significant increase of
      HC in control cells (from 1.37 +/- 0.12 to 1.64 +/- 0.18 MUL/mm Hg/min/cm(2), P <
      0.05), but not in senescent cells (1.15 +/- 0.17 and 1.08 +/- 0.10 MUL MUL/mm
      Hg/min/cm(2)). TEER changes were consistent with the HC results. Western blot
      analysis showed that the expression level of myosin light chain, claudin-5, and
      VE-cadherin significantly reduced under pressure elevation in control cells but
      not in senescent cells. CONCLUSIONS: AAP cells are mechano-sensitive; however,
      cell senescence rendered the cells less responsive to mechanical stimulus, which
      may have pathological consequences.

PMID- 24576880
TI  - Characterization of vitamin D production by human ocular barrier cells.
AB  - PURPOSE: Vitamin D3 is a secosteroid mainly synthesized from the conversion of
      the skin precursor 7-dehydrocholesterol (7DHC) to vitamin D3 by ultraviolet (UV)
      B sunlight. Extrarenal synthesis of vitamin D3 has been reported in many tissues
      and cells, including barrier sites. This study characterizes the expression of
      components of vitamin D3 signaling in human ocular barrier cells. METHODS:
      Primary human scleral fibroblasts (HSF), human corneal endothelial (HCEC-12),
      nonpigmented ciliary body epithelial (ODM-2), and adult retinal pigment
      epithelial (ARPE-19) cell lines were analyzed for the expression of vitamin D
      receptor (VDR), the vitamin D3 activating enzymes 1alpha-hydroxylase (CYP27B1),
      25-hydroxylases (CYP27A1 and CYP2R1), the vitamin D3 inactivating enzyme 24
      hydroxylase (CYP24A1), and the endocytic receptors cubilin and megalin using a
      combination of RT-PCR, immunocytochemistry, and enzyme immunoassay (EIA).
      RESULTS: The HSF, HCEC-12, ODM-2, and ARPE-19 express mRNA and protein for all
      vitamin D3 synthesizing and metabolizing components. The cell types tested,
      except HSF, are able to convert inactive 25-hydroxyvitamin D3 (25[OH]D3) into
      active 1,25-hydroxyvitamin D3 (1,25[OH]2D3). CONCLUSIONS: This novel study
      demonstrated that ocular barrier epithelial cells express the machinery for
      vitamin D3 and can produce 1,25(OH)2D3. We suggest that vitamin D3 might have a
      role in immune regulation and barrier function in ocular barrier epithelial
      cells.

PMID- 24576882
TI  - Genetic and environmental risk factors for age-related macular degeneration in
      persons 90 years and older.
AB  - PURPOSE: We studied associations of genetic polymorphisms in age-related
      maculopathy susceptibility 2 (ARMS2) and complement factor H (CFH) in
      nonagenarians with age-related macular degeneration (AMD). METHODS: This case
      control study comprised 2737 persons (1204 controls, 1433 AMD cases), including
      166 nonagenarians (52 controls, 114 AMD cases). Single nucleotide polymorphisms
      (SNPs) in the genes ARMS2 and CFH were determined. Risk scores were computed by
      multiple logistic regression analysis, including genetic and environmental risk
      factors (smoking, hypertension, body mass index, diabetes) for different age
      groups (<70, 70-79, 80-89, >= 90 years [nonagenarians]). RESULTS: In
      nonagenarians, ARMS2 showed the weakest associations with AMD (odds ratio [OR] =
      1.52, P = 0.127) compared to the other groups (OR, 70 years = 2.23, P = 1.03 *
      10(-13); OR, 70-79 years = 2.70, P = 1.00 * 10(-13); OR, 80-89 years = 3.11, P =
      6.56 * 10(-8)). For CFH, ORs for AMD increased with age (<70 years OR = 1.96, P =
      1.80 * 10(-11); 70-79 years OR = 1.89, P = 4.48 * 10(-13); 80-89 years OR = 2.71,
      P = 1.28 * 10(-7)), but decreased again in the nonagenarians (OR = 2.21, P =
      0.005). Compared to the group <70 years, reduced minor allele frequencies (MAFs)
      for AMD patients were observed in the nonagenarians (CFH 0.54 vs. 0.43, P =
      0.009; ARMS2 0.44 vs. 0.29, P = 2.97 * 10(-5)), while the MAFs in controls were
      not significantly different. The genetic risk score revealed the lowest
      discriminative power in the nonagenarians with an area-under-curve (AUC) of 0.658
      for receiver-operating characteristics (AUC 80-89 years = 0.768, 70-79 years =
      0.704, <70 years = 0.682), while no significant difference was seen for the
      environmental risk score (AUC < 70 years = 0.579, 70-79 years = 0.567, 80-89
      years = 0.600, >90 years = 0.608). CONCLUSIONS: Risk alleles in CFH and ARMS2
      have a significantly smaller effect on AMD development in nonagenarians, while
      environmental factors retain a similar effect.

PMID- 24576883
TI  - Effects of metal(loid)-based nanomaterials on essential element homeostasis: the
      central role of nanometallomics for nanotoxicology.
AB  - The growing use of engineered nanomaterials in both commercial products and
      biomedical applications leads to increasing exposure for production line workers,
      consumers and patients. Therefore, the understanding of biological effects
      induced by nanomaterials is crucial for their safety assessment. An important
      group of nanomaterials is represented by metal(loid)-based nanoparticles, because
      of their unique physico-chemical properties. Metal(loid)-based nanoparticles
      themselves, the related ion release, and their nanometallomes, can potentially
      interact with essential elements causing dys-homeostasis and adverse biological
      effects. In this work, we describe the effects of metal(loid)-based nanoparticles
      on essential element homeostasis. In particular, we consider the most used and
      promising metal(loid)-based nanoparticles, highlighting that the new emerging
      concept of nanometallomics is important to disclose the impact of these
      nanoparticles on human health and the related long-term effects. 

PMID- 24576884
TI  - Human-induced pluripotent stem cell models of inherited cardiomyopathies.
AB  - PURPOSE OF REVIEW: This article provides an overview of the latest advances in in
      vitro modeling of inherited cardiomyopathies using human-induced pluripotent stem
      cells (iPSCs). RECENT FINDINGS: Inherited cardiomyopathies have been recently
      modeled by generating iPSCs from patients harboring mutations in genes associated
      with the pathogenesis of hypertrophic cardiomyopathy, dilated cardiomyopathy, and
      arrhythmogenic right ventricular cardiomyopathy/dysplasia. SUMMARY: Patient
      specific iPSCs and their differentiated cardiomyocytes (induced pluripotent stem
      cell-derived cardiomyocytes) now provide a novel model to study the underlying
      molecular mechanism of the pathogenesis of familial cardiomyopathies as well as
      for in-vitro drug screening and drug discovery.

PMID- 24576885
TI  - Safety and immunogenicity of 13-valent pneumococcal conjugate vaccine
      formulations with and without aluminum phosphate and comparison of the
      formulation of choice with 23-valent pneumococcal polysaccharide vaccine in
      elderly adults: a randomized open-label trial.
AB  - This randomized open-label trial was designed to provide preliminary
      immunogenicity and safety data to support development of the pediatric 13-valent
      pneumococcal conjugate vaccine (PCV13) for adults. The aims were to: identify an
      age-appropriate PCV13 formulation, i.e., with (n = 309) or without (n = 304)
      aluminum phosphate (AlPO 4); compare the selected PCV13 formulation (n = 309)
      with 23-valent pneumococcal polysaccharide vaccine (PPSV23; n = 301); and,
      together with an extension study, assess sequential use of pneumococcal vaccines
      at 1-year intervals in adults aged >=65 years (n = 105) not pre-vaccinated with
      PPSV23. Immune responses were measured by ELISA and opsonophagocytic activity
      assays 1 month postvaccination. Immunoglobulin G responses elicited by PCV13 with
      AlPO 4 and PCV13 without AlPO 4 were similar for the majority, and noninferior
      for all PCV13 serotypes. PCV13 with AlPO 4 was generally more reactogenic, with
      reactions mainly mild or moderate. Thus, PCV13 with AlPO 4 (hereafter PCV13)
      became the selected formulation. Immune responses to PCV13 were noninferior for
      all but one serotype and for most PCV13 serotypes superior to PPSV23. Vaccine
      sequence assessments showed that for PCV13/PPSV23, the initial PCV13 dose
      generally enhanced responses to a subsequent PPSV23 dose, compared with PPSV23
      alone. For PCV13/PCV13, a second dose did not enhance the first dose response
      when given after 1 year. For PCV13/PPSV23/PCV13, priming with PCV13 (vaccination
      1) did not protect against lower responses induced by PPSV23 to subsequent PCV13
      (vaccination 3). In conclusion, the pediatric PCV13 formulation with AlPO 4 is
      well tolerated and immunogenic in adults, is generally more immunogenic than
      PPSV23, and subsequent vaccination with PPSV23 is possible if required.

PMID- 24576887
TI  - Bothun et al.; Infant aphakic treatment study group: One-year strabismus outcomes
      in the Infant Aphakia Treatment Study (Ophthalmology 2013;120:1227-31).

PMID- 24576886
TI  - Collagen cross-linking with photoactivated riboflavin (PACK-CXL) for the
      treatment of advanced infectious keratitis with corneal melting.
AB  - PURPOSE: To investigate the efficacy and safety of corneal collagen cross-linking
      (CXL) with photoactivated riboflavin (photoactivated chromophore for infectious
      keratitis [PACK]-CXL) in the management of infectious keratitis with corneal
      melting. DESIGN: Prospective clinical trial. PARTICIPANTS: Forty eyes from 40
      patients with advanced infectious keratitis and coexisting corneal melting.
      METHODS: Twenty-one patients (21 eyes) underwent PACK-CXL treatment in addition
      to antimicrobial therapy. The control group consisted of 19 patients (19 eyes)
      who received only antimicrobial therapy. MAIN OUTCOME MEASURES: The slit-lamp
      characteristics of the corneal ulceration, corrected distance visual acuity,
      duration until healing, and complications were documented in each group. The Mann
      Whitney U test was used for statistical analysis. P values less than 0.05 were
      considered statistically significant. RESULTS: The average time until healing was
      39.76 +/- 18.22 days in the PACK-CXL group and 46.05 +/- 27.44 days in the
      control group (P = 0.68). After treatment and healing, corrected distance visual
      acuity was 1.64 +/- 0.62 in the PACK-CXL group and 1.67 +/- 0.48 in the control
      group (P = 0.68). The corneal ulceration's width and length was significantly
      bigger in the PACK-CXL group (P = 0.004 and P = 0.007). Three patients in the
      control group demonstrated corneal perforation; infection recurred in 1 of them.
      No serious complications occurred in the PACK-CXL group. CONCLUSIONS: Corneal CXL
      with photoactivated riboflavin did not shorten the time to corneal healing;
      however, the complication rate was 21% in the control group, whereas there was no
      incidence of corneal perforation or recurrence of the infection in the PACK-CXL
      group. These results indicate that PACK-CXL may be an effective adjuvant therapy
      in the management of severe infectious keratitis associated with corneal melting.

PMID- 24576881
TI  - Limited change in anisometropia and aniso-axial length over 13 years in myopic
      children enrolled in the Correction of Myopia Evaluation Trial.
AB  - PURPOSE: We investigated changes in anisometropia and aniso-axial length with
      myopia progression in the Correction of Myopia Evaluation Trial (COMET) cohort.
      METHODS: Of 469 myopic children, 6 to <12 years old, enrolled in COMET, 358 were
      followed for 13 years. Cycloplegic autorefraction and axial length (AL) in each
      eye were measured annually. The COMET eligibility required anisometropia
      (interocular difference in spherical equivalent refraction) of <= 1.00 diopter
      (D). For each child, a linear regression line was fit to anisometropia data by
      visit, and the regression slope b was used as the rate of change. Logistic
      regression was applied to identify factors for significant changes in
      anisometropia (b >= 0.05 D/y, or a cumulative increase in anisometropia >= 0.50 D
      over 10 years). Similar analyses were applied to aniso-AL. RESULTS: A total of
      358/469 (76.3%) children had refractions at baseline and the 13-year visit. The
      mean (SD) amount of anisometropia increased from 0.24 D (0.22 D) at baseline to
      0.49 D (0.46 D) at the 13-year visit. A total of 319/358 (89.1%) had slopes |b| <
      0.05 D/y and 39 (10.9%) had slopes |b| >= 0.05 D/y, with only one negative slope.
      Similarly, 334/358 (93.3%) children had little change in aniso-AL over time. The
      correlation between changes in anisometropia and aniso-AL over 13 years was 0.39
      (P < 0.001). The correlation between changes in anisometropia and myopia
      progression was significant (r = -0.36, P < 0.001). No correlation was found
      between baseline anisometropia and myopia progression (r = -0.02, P = 0.68).
      CONCLUSIONS: Myopia and axial length progressed at a similar rate in both eyes
      for most children in COMET during the period of fast progression and eventual
      stabilization. These results may be more generalizable to school-aged myopic
      children with limited anisometropia at baseline. (ClinicalTrials.gov number,
      NCT00000113.).

PMID- 24576888
TI  - Development and validation of quality-of-life questionnaires for birdshot
      chorioretinopathy.

PMID- 24576889
TI  - Retinal vasculitis imaging by adaptive optics.

PMID- 24576890
TI  - Antifouling and toxic properties of the bioactive metabolites from the seagrasses
      Syringodium isoetifolium and Cymodocea serrulata.
AB  - The present study documents the antifouling and toxic properties of seagrasses
      Syringodium isoetifolium and Cymodocea serrulata. For that, the seagrasses S.
      isoetifolium and C. serrulata were extracted individually using organic solvents
      viz. dichloromethane, acetone and methanol. Amongst the extracts, the maximum
      antimicrofouling and antimacrofouling activities were exhibited by methanol
      extracts of both the seagrasses. The Minimal Inhibitory Concentration (MIC) of
      methanolic extracts of seagrasses was ranged from 1.0 to 10ug/ml against test
      biofilm bacteria and microalgal strains. Similarly, 100% fouling inhibition of
      limpet Patella vulgata was found at 6.0mg/ml of methanolic extracts of
      seagrasses. The mussel Perna indica showed 50% of byssal production and
      attachment inhibition at 21.51+/-2.03, 17.82+/-1.07ug/ml and the anticrustaecean
      activity for 50% mortality of Artemia salina was recorded at 732.14+/-9.21 and
      394.16+/-5.16ug/ml respectively for methanolic extracts of S. isoetifolium and C.
      serrulata. The minimal inhibitory and higher lethal concentrations of active
      methanol extracts shows it's less toxic nature. Based on the prolific results,
      methanol extracts of S. isoetifolium and C. serrulata were subjected to
      purification using silica gel column and thin layer chromatography. Then the
      active compounds of the bioassay guided fractions were partially characterized
      using gas chromatography coupled with mass spectroscopy (GC-MS) and keyed out
      that fatty acids (C16 to C24) were the major components which responsible for the
      antifouling properties of the candidate seagrasses. 

PMID- 24576891
TI  - Shedding new light on lipid functions with CARS and SRS microscopy.
AB  - Modern optical microscopy has granted biomedical scientists unprecedented access
      to the inner workings of a cell, and revolutionized our understanding of the
      molecular mechanisms underlying physiological and disease states. In spite of
      these advances, however, visualization of certain classes of molecules (e.g.
      lipids) at the sub-cellular level has remained elusive. Recently developed
      chemical imaging modalities - Coherent Anti-Stokes Raman Scattering (CARS)
      microscopy and Stimulated Raman Scattering (SRS) microscopy - have helped bridge
      this gap. By selectively imaging the vibration of a specific chemical group,
      these non-invasive techniques allow high-resolution imaging of individual
      molecules in vivo, and circumvent the need for potentially perturbative extrinsic
      labels. These tools have already been applied to the study of fat metabolism,
      helping uncover novel regulators of lipid storage. Here we review the underlying
      principle of CARS and SRS microscopy, and discuss the advantages and caveats of
      each technique. We also review recent applications of these tools in the study of
      lipids as well as other biomolecules, and conclude with a brief guide for
      interested researchers to build and use CARS/SRS systems for their own research.
      This article is part of a Special Issue entitled Tools to study lipid functions. 

PMID- 24576892
TI  - Caveolin-1 interacts with ATP binding cassette transporter G1 (ABCG1) and
      regulates ABCG1-mediated cholesterol efflux.
AB  - ATP-binding cassette transporter G1 (ABCG1) plays an important role in macrophage
      reverse cholesterol transport in vivo by promoting cholesterol efflux onto
      lipidated apoA-I. However, the underlying mechanism is unclear. Here, we found
      that ABCG1 co-immunoprecipitated with caveolin-1 (CAV1) but not with flotillin-1
      and -2. Knockdown of CAV1 expression using siRNAs significantly reduced ABCG1
      mediated cholesterol efflux without detectable effect on ABCA1-mediated
      cholesterol efflux. Disruption of the putative CAV1 binding site in ABCG1,
      through replacement of tyrosine residues at positions 487 and 489 or at positions
      494 and 495 with alanine (Y487AY489A and Y494AY495A), impaired the interaction of
      ABCG1 with CAV1 and significantly decreased ABCG1-mediated cholesterol efflux.
      The substitution of Tyr494 and Tyr495 with Phe or Trp that resulted in an intact
      CAV1 binding site had no effect. Furthermore, Y494AY495A affected trafficking of
      ABCG1 to the cell surface. The mutant protein is mainly located intracellularly.
      Finally, we found that CAV1 co-immunoprecipitated with ABCG1 and regulated
      cholesterol efflux to reconstituted HDL in THP-1-derived macrophages upon the
      liver X receptor agonist treatment. These findings indicate that CAV1 interacts
      with ABCG1 and regulates ABCG1-mediated cholesterol efflux. 

PMID- 24576893
TI  - Bolus administration of intravenous glucose in the treatment of hyperkalemia: a
      randomized controlled trial.
AB  - BACKGROUND: Hyperkalemia is a common medical emergency that may result in serious
      cardiac arrhythmias. Standard therapy with insulin plus glucose reliably lowers
      the serum potassium concentration ([K(+)]) but carries the risk of hypoglycemia.
      This study examined whether an intravenous glucose-only bolus lowers serum [K(+)]
      in stable, nondiabetic, hyperkalemic patients and compared this intervention with
      insulin-plus-glucose therapy. METHODS: A randomized, crossover study was
      conducted in 10 chronic hemodialysis patients who were prone to hyperkalemia.
      Administration of 10 units of insulin with 100 ml of 50% glucose (50 g) was
      compared with the administration of 100 ml of 50% glucose only. Serum [K(+)] was
      measured up to 60 min. Patients were monitored for hypoglycemia and EKG changes.
      RESULTS: Baseline serum [K(+)] was 6.01 +/- 0.87 and 6.23 +/- 1.20 mmol/l in the
      insulin and glucose-only groups, respectively (p = 0.45). At 60 min, the glucose
      only group had a fall in [K(+)] of 0.50 +/- 0.31 mmol/l (p < 0.001). In the
      insulin group, there was a fall of 0.83 +/- 0.53 mmol/l at 60 min (p < 0.001) and
      a lower serum [K(+)] at that time compared to the glucose-only group (5.18 +/-
      0.76 vs. 5.73 +/- 1.12 mmol/l, respectively; p = 0.01). In the glucose-only
      group, the glucose area under the curve (AUC) was greater and the insulin AUC was
      smaller. Two patients in the insulin group developed hypoglycemia. CONCLUSION:
      Infusion of a glucose-only bolus caused a clinically significant decrease in
      serum [K(+)] without any episodes of hypoglycemia.

PMID- 24576894
TI  - Long-term survival after simultaneous pancreas-kidney transplantation with
      primary function of at least one year--a single-center experience.
AB  - BACKGROUND: Simultaneous pancreas-kidney transplantation has been established as
      the treatment of choice for type 1 diabetes patients with renal dysfunction.
      Patient 1-year survival better than 95% has been achieved using this kind of
      transplantation. According to the postoperative complication rate (5% mortality),
      recipients appear to have a survival benefit not earlier than 2 years after
      transplantation. This study evaluates the long-term benefit of simultaneous
      pancreas-kidney recipients with functioning grafts after 1 year.
      MATERIAL/METHODS: A retrospective analysis of 176 patients after first
      transplantation with functioning grafts 1 year after simultaneous pancreas-kidney
      transplantation was performed. RESULTS: During the follow-up period starting 1
      year after successful transplantation, 7 patients died due to various causes, 13
      pancreas grafts (7.4%) and 13 kidney transplants (7.4%) lost their function
      during the 10-year follow-up period. Chronic graft failure was the most common
      reason for transplant loss. CONCLUSIONS: Our data support the excellent long-term
      prognosis of simultaneous pancreas-kidney transplantation recipients with
      functioning graft 1 year after transplantation.

PMID- 24576895
TI  - Hyoscine N-butylbromide (Buscopan(r)) in the treatment of acute ureteral colic:
      what is the evidence?
AB  - OBJECTIVE: To investigate the evidence for the use of hyoscine N-butylbromide
      (HBB) in the treatment of acute renal colic. METHODS: A literature search was
      performed using the keywords 'hyoscine N-butylbromide', 'ureteral colic',
      'spasmolytic', 'anticholinergic' and 'analgesia'. The articles were given the
      appropriate level of evidence according to the Oxford Centre for Evidence-Based
      Medicine Levels of Evidence guidelines. RESULTS: The analgesic effect of HBB as
      monotherapy is inferior to that of opioids and/or non-steroidal anti-inflammatory
      drugs (NSAIDs). It does provide an analgesic and antispasmodic effect, but not as
      long-lasting as NSAIDs. HBB does not serve as an adjunct to opioids. Furthermore,
      it does not facilitate passage of ureteral stones and has no effect on expulsion
      rate. CONCLUSIONS: HBB is often used where urinary tract smooth muscle spasm is
      thought to be part of the pathophysiological process. According to the evidence,
      administration of HBB follows non-peer-reviewed protocols which are based on
      empiric recommendations. Its role is still unclear, as it appears to have no
      advantage when used as monotherapy over established forms of analgesia. There
      appears to be a time-dependent relation to pain reduction following parenteral
      administration, but this needs to be confirmed by more prospective randomized
      cohorts.

PMID- 24576897
TI  - Rho-directed forces in collective migration.
AB  - Collective cell migration depends on multicellular mechanocoupling between leader
      and follower cells to coordinate traction force and position change. Co
      registration of Rho GTPase activity and forces in migrating epithelial cell
      sheets now shows how RhoA controls leader-follower cell hierarchy, multicellular
      cytoskeletal contractility and mechanocoupling, to prevent ectopic leading edges
      and to move the cell sheet forward. 

PMID- 24576898
TI  - SIK2 regulates insulin secretion.
AB  - Correct regulation of insulin secretion by the pancreas is crucial for organismal
      function and survival. The AMPK-related kinase SIK2 (salt-inducible kinase 2) is
      now shown to be stabilized in pancreatic beta-cells following glucose
      stimulation, leading to improved systemic glucose homeostasis by regulating
      cellular calcium flux and insulin secretion. 

PMID- 24576896
TI  - Impact of genomic damage and ageing on stem cell function.
AB  - Impairment of stem cell function contributes to the progressive deterioration of
      tissue maintenance and repair with ageing. Evidence is mounting that age
      dependent accumulation of DNA damage in both stem cells and cells that comprise
      the stem cell microenvironment are partly responsible for stem cell dysfunction
      with ageing. Here, we review the impact of the various types of DNA damage that
      accumulate with ageing on stem cell functionality, as well as the development of
      cancer. We discuss DNA-damage-induced cell intrinsic and extrinsic alterations
      that influence these processes, and review recent advances in understanding
      systemic adjustments to DNA damage and how they affect stem cells. 

PMID- 24576899
TI  - A microRNA-operated switch of asymmetric-to-symmetric cancer stem cell divisions.
AB  - Defective asymmetric cell divisions of stem and progenitor cells are associated
      with tumorigenesis by a largely unknown mechanism. A signalling axis involving
      Snail, microRNA-146a and Numb is now shown to regulate the switch between
      symmetric and asymmetric cell division in colorectal cancer stem cells. 

PMID- 24576904
TI  - Axillary metastases from occult breast cancer. Our experience.
AB  - We report the case of a 63-year-old woman with occult breast cancer who presented
      with a hard metastatic nodule in the left axilla. Although histology identified a
      metastatic carcinoma in the lymph nodes, numerous tests failed to detect the
      primary tumor. Resected lymph node was positive for both estrogen and
      progesterone receptors, suggesting the breast as the site of the primary tumor.
      Left modified radical mastectomy was performed. Pathology revealed an invasive
      lobular carcinoma (2.5 x 2 mm in size) with extensive lymphatic involvement,
      which strongly expressed both vascular endothelial growth factor-C (VEGF-C) and
      VEGF-D.

PMID- 24576905
TI  - Regional patterns of (15)N natural abundance in forest ecosystems along a large
      transect in eastern China.
AB  - The regional determining factors underlying inter- and intra-site variation of
      (15)N natural abundance in foliage, O horizon and mineral soil were investigated
      in eastern China.(15)N natural abundance values for these forest ecosystems were
      in the middle of the range of values previously found for global forest
      ecosystems. In contrast to commonly reported global patterns, temperate forest
      ecosystems were significantly more(15)N-enriched than tropical forest ecosystems,
      and foliage delta(15)N was negatively correlated with increasing mean annual
      temperature and net soil N mineralisation in eastern China. Tight N cycling in
      forest ecosystems and the use of atmospheric N deposition by trees might underlie
      the delta(15)N distribution patterns in eastern China. The existence of
      mycorrhizal fungi and root distribution profiles in the soil may also influence
      the(15)N natural abundance patterns in forest ecosystems of eastern China. 

PMID- 24576906
TI  - T cells in organ ischemia reperfusion injury.
AB  - PURPOSE OF REVIEW: Ischemia and reperfusion injuries occur in multiple clinical
      settings and contribute to organ dysfunction/failures. Despite the innate
      inflammatory immune nature, T cells that are critically involved in the
      pathogenesis of ischemia reperfusion injury (IRI), include not only CD4+ T cells,
      but also CD8+ and gammadeltaT cells. This review focuses on questions of how
      putative Ag-specific T cells are involved, which include whether they function in
      an Ag-dependent manner; how they function, cytokine-mediated or costimulatory
      molecule-mediated mechanisms; and whether different T-cell subsets, Th1, Th17,
      regulatory T cell (Treg), are all involved and play distinctive roles? RECENT
      FINDINGS: Specific T-cell populations, such as effector memory CD4 T cells,
      promote inflammatory immune activation by ischemia reperfusion independent of
      their adaptive properties, that is Ag-independently. They function by secreting
      cytokines and expressing costimulatory molecules to either promote or inhibit
      innate immune activation, or facilitate tissue repair/homeostasis, as exemplified
      by Th1, Th17 or Th2, Treg cells, respectively. SUMMARY: T-cell-targeted therapies
      need to be refined with strategies to maximally eliminate the proinflammatory but
      spare the anti-inflammatory/immune regulatory properties of T cells, for future
      clinical application to ameliorate IRI.

PMID- 24576907
TI  - Immune response to the HPV-16/18 AS04-adjuvanted vaccine administered as a 2-dose
      or 3-dose schedule up to 4 years after vaccination: results from a randomized
      study.
AB  - This randomized, partially-blind study (ClinicalTrials.gov registration number
      NCT00541970) evaluated the immunogenicity and safety of 2-dose (2D) schedules of
      the HPV-16/18 AS04-adjuvanted vaccine. Results to month (M) 24 have been reported
      previously and we now report data to M48 focusing on the licensed vaccine
      formulation (20 MUg each of HPV-16 and -18 antigens) administered at M0,6
      compared with the standard 3-dose (3D) schedule (M0,1,6). Healthy females (age
      stratified: 9-14, 15-19, 20-25 years) were randomized to receive 2D at M0,6 (n =
      240) or 3D at M0,1,6 (n = 239). In the according-to-protocol immunogenicity
      cohort, all initially seronegative subjects seroconverted for HPV-16 and -18
      antibodies and remained seropositive up to M48. For both HPV-16 and -18,
      geometric mean antibody titer (GMT) ratios (3D schedule in women aged 15-25 years
      divided by 2D schedule in girls aged 9-14 years) at M36 and M48 were close to 1,
      as they were at M7 when non-inferiority was demonstrated. The kinetics of HPV-16,
      -18, -31, and -45 antibody responses were similar for both groups and HPV-16 and 
      18 GMTs were substantially higher than natural infection titers. The vaccine had
      a clinically acceptable safety profile in both groups. In summary, antibody
      responses to a 2D M0,6 schedule of the licensed vaccine formulation in girls aged
      9-14 years appeared comparable to the standard 3D schedule in women aged 15-25
      years up to 4 years after first vaccination. A 2D schedule could facilitate
      implementation of HPV vaccination programs and improve vaccine coverage and
      series completion rates. 

PMID- 24576908
TI  - A dihydro-pyrido-indole potently inhibits HSV-1 infection by interfering the
      viral immediate early transcriptional events.
AB  - In our continued quest for identifying novel molecules from ethnomedicinal source
      we have isolated an alkaloid 7-methoxy-1-methyl-4,9-dihydro-3H-pyrido[3,4
      b]indole, also known as Harmaline (HM), from an ethnomedicinal herb Ophiorrhiza
      nicobarica. The compound exhibited a potent anti-HSV-1 activity against both wild
      type and clinical isolates of HSV-1. Further we demonstrated that HM did not
      interfere in viral entry but the recruitment of lysine-specific demethylase-1
      (LSD1) and the binding of immediate-early (IE) complex on ICP0 promoter. This
      leads to the suppression of viral IE gene synthesis and thereby the reduced
      expression of ICP4 and ICP27. Moreover, HM at its virucidal concentration is
      nontoxic and reduced virus yields in cutaneously infected Balb/C mice. Thus, the
      interference in the binding of IE complex, a decisive factor for HSV lytic cycle
      or latency by HM reveals an interesting target for developing non-nucleotide
      antiherpetic agent with different mode of action than Acyclovir. 

PMID- 24576910
TI  - Efficacy of combined therapy with cyclosporin and low-dose prednisolone in
      interstitial pneumonia associated with connective tissue disease.
AB  - BACKGROUND: The optimal treatment method for interstitial pneumonia (IP) with
      connective tissue disease (CTD) remains controversial. In addition, a clinically
      meaningful end point to judge drug efficacy has not been fully investigated.
      OBJECTIVES: The aim of this study was to evaluate, from various aspects, the
      therapeutic benefit and tolerability of combined therapy with cyclosporin A (CsA)
      and low-dose prednisolone (PSL) for chronic fibrosing CTD-IP patients. METHODS: A
      total of 26 CTD-IP patients diagnosed by surgical lung biopsy and subsequently
      treated with the above combination therapy were retrospectively reviewed. The
      therapeutic regimen comprised methylprednisolone induction therapy for 2-4 weeks,
      followed by a combined therapy of CsA with low-dose PSL for 1 year. Evaluation of
      the therapeutic benefit was based on not only pulmonary function but also
      exercise capacity, health-related quality of life and dyspnea. RESULTS: After 1
      year of therapy, clinically significant improvements in forced vital capacity
      (>=10%), carbon monoxide diffusing capacity of the lung (>=15%), 6-min walk
      distance (>=28 m), and St. George's Respiratory Questionnaire (<=-7) were
      observed in 61.5, 69.2, 61.5 and 69.2% of the patients, respectively. All
      measurements showed statistically significant improvements compared with baseline
      values. The 1-year treatment did not need to be discontinued in any patients due
      to unacceptable toxicity, and no deaths occurred. CONCLUSIONS: Combined therapy
      with CsA and low-dose PSL for CTD-IP patients was well-tolerated and patients
      displayed a noteworthy response.

PMID- 24576911
TI  - Interleukin-6 enhances manganese accumulation in SH-SY5Y cells: implications of
      the up-regulation of ZIP14 and the down-regulation of ZnT10.
AB  - Exposure to an excess amount of manganese causes neurological symptoms similar to
      Parkinson's disease. Zinc transporters such as Zrt, Irt-related protein 8 (ZIP8),
      and ZIP14 have been shown to have affinities for Mn(2+) as well as Zn(2+), but
      their roles in Mn(2+) uptake in neuronal cells remain unclear. Recent studies
      have shown that another zinc transporter ZnT10 may be involved in manganese
      excretion. Here we examined the roles of ZIP8, ZIP14, and ZnT10 in the transport
      of manganese in human SH-SY5Y neuroblastoma cells. The introduction of siRNA of
      ZIP14 decreased the uptake of Mn(2+), suggesting a significant role of ZIP14 in
      Mn(2+) uptake in SH-SY5Y cells. The pretreatment of SH-SY5Y cells with
      interleukin-6 (IL-6) markedly increased the accumulation of manganese to approx.
      3-fold that of the control, which could be partly explained by the increased
      uptake of Mn(2+) due to the up-regulation of ZIP14 by IL-6. The treatment of SH
      SH5Y cells with IL-6 clearly decreased both the mRNA and protein levels of ZnT10
      with a concomitant decrease in the manganese excretion efficiency. These results
      suggest that both the up-regulation of ZIP14 and the down-regulation of ZnT10 by
      IL-6 might have enhanced the accumulation of manganese in SH-SY5Y cells. Our
      results provide new insight into the roles of zinc transporters in the aberrant
      manganese accumulation in neuronal cells, particularly in the presence of
      inflammatory cytokines such as IL-6. 

PMID- 24576913
TI  - Preface.

PMID- 24576914
TI  - Introduction.

PMID- 24576912
TI  - Face Arm Speech Time Test use in the prehospital setting, better in the ambulance
      than in the emergency medical communication center.
AB  - BACKGROUND: Prehospital identification of acute stroke increases the possibility
      of early treatment and good outcome. To increase identification of stroke, the
      Face Arm Speech Time (FAST) test was introduced in the Emergency Medical
      Communication Center (EMCC). This substudy aims to evaluate the implementation of
      the FAST test in the EMCC and the ambulance service. METHODS: The study was
      conducted in the region of Stockholm, Sweden during 6 months. The study
      population consisted of all calls to the EMCC concerning patients presenting at
      least one FAST symptom or a history/finding making the EMCC or ambulance
      personnel to suspect stroke within 6 h. Positive FAST was compared to diagnosis
      at discharge. Positive predictive values (PPV) for a stroke diagnosis at
      discharge were calculated. RESULTS: In all, 900 patients with a median age of 71
      years were enrolled, 667 (74%) by the EMCC and 233 (26%) by the ambulances. At
      discharge, 472 patients (52%) were diagnosed with stroke/transient ischemic
      attack (TIA), 337 identified by the EMCC (71%) and 135 (29%) by the ambulances.
      The PPV for a discharge diagnosis of stroke/TIA was 51% (CI 47-54%) in EMCC
      enrolled and 58% (CI 52-64%) in ambulance-enrolled patients. With a positive FAST
      the PPV of a correct stroke/TIA diagnosis increased to 56% (CI 52-61%) and 73%
      (CI 66-80%) in EMCC- and ambulance-enrolled patients, respectively. Positive FAST
      from EMCC was also found in 44% of patients with a nonstroke diagnosis at
      discharge. A stroke/TIA diagnosis at discharge but negative FAST was found in 58
      and 27 patients enrolled by the EMCC and ambulances, respectively. CONCLUSIONS:
      The PPV of FAST is higher when used on the scene by ambulance than by EMCC. FAST
      may be a useful prehospital tool to identify stroke/TIA but has limitations as
      the test can be negative in true strokes, can be positive in nonstrokes, and FAST
      symptoms may be present but not identified in the emergency call. For the
      prehospital care situation better identification tools are needed.

PMID- 24576915
TI  - Lung volumes and forced ventilatory flows.

PMID- 24576916
TI  - Standardization of the measurement of transfer factor (diffusing capacity).

PMID- 24576917
TI  - Standardized challenge testing with pharmacological, physical and sensitizing
      stimuli in adults.

PMID- 24576918
TI  - Symbols, abbreviations and units.

PMID- 24576919
TI  - Lower eyelid tension in young adults determined by a simple lid tensiometer.
AB  - PURPOSE: Eyelid tension seems to be related to corneal astigmatism and to affect
      the ocular surface. The aim of this study is to determine the lower eyelid
      tension in young adults with a simple lid tensiometer. METHODS: A commercially
      available precision digital pressure gauge that was connected to a pressure
      guided tube full of water with a sensor at its end being placed between the lower
      eyelid and ocular surface was used as the lid tensiometer to measure the lower
      eyelid pressure at the central lid in 8 male and 12 female subjects aged between
      20 and 39 years with normal healthy eyes. Measurements were respectively
      performed by 2 operators under the same conditions to test possible interoperator
      variation. RESULTS: The lower eyelid pressures of the 20 subjects measured by 2
      operators at the central lid were 445.28 +/- 121.17 and 458.65 +/- 127.15 Pa,
      respectively. The test of interoperator variation demonstrated that there was
      good agreement between 2 operators (intraclass correlation coefficient = 0.965, F
      = 56.09, P < 0.001). CONCLUSIONS: Our simple lid tensiometer is a viable option
      for measuring eyelid pressure with good repeatability.

PMID- 24576920
TI  - A new nonhuman primate model of severe dry eye.
AB  - PURPOSE: The aim of this study was to establish a new rhesus monkey model of
      severe dry eye. METHODS: A total of 8 rhesus monkeys were used for the study.
      Four monkeys had their main lacrimal gland and nictitating membrane surgically
      removed (group 1). Another 4 monkeys had a similar surgery with further
      application of 50% trichloroacetic acid on the bulbar conjunctiva (group 2). The
      ocular surface was evaluated before and after the surgery (1, 4, 8, 12, and 24
      weeks) using Schirmer-1 test, corneal fluorescein staining, and the lissamine
      green test. Conjunctival impression cytology was also performed before and 24
      weeks after the surgery. Finally, the cornea and the conjunctiva were evaluated
      using light microscopy. RESULTS: A significant decrease in tear secretion was
      observed in all operated eyes. Schirmer test data measured were <=4 mm in all the
      operated eyes. Slit-lamp examination also revealed abnormal staining in all the
      operated eyes that remained stable until the end of the experiment. In group 2,
      corneal fluorescein staining and lissamine green test values were always >=5 (max
      12) and >=4 (max 9), respectively. Impression cytology specimens of both the
      treated groups showed conjunctival squamous metaplasia and a decreased number of
      goblet cells. Under light microscopy, the corneal epithelium appeared irregular
      with edematous basal epithelial cells. The conjunctiva showed a decreased goblet
      cell density with infiltration of inflammatory cells. CONCLUSIONS: Complete
      removal of the principal lacrimal gland and nictitating membrane associated with
      the application of 50% trichloroacetic acid on the conjunctiva could induce
      severe dry eye in rhesus monkeys.

PMID- 24576921
TI  - Reply.

PMID- 24576922
TI  - Kinetic modelling of growth and storage molecule production in microalgae under
      mixotrophic and autotrophic conditions.
AB  - In order to improve algal biofuel production on a commercial-scale, an
      understanding of algal growth and fuel molecule accumulation is essential. A
      mathematical model is presented that describes biomass growth and storage
      molecule (TAG lipid and starch) accumulation in the freshwater microalga
      Chlorella vulgaris, under mixotrophic and autotrophic conditions. Biomass growth
      was formulated based on the Droop model, while the storage molecule production
      was calculated based on the carbon balance within the algal cells incorporating
      carbon fixation via photosynthesis, organic carbon uptake and functional biomass
      growth. The model was validated with experimental growth data of C. vulgaris and
      was found to fit the data well. Sensitivity analysis showed that the model
      performance was highly sensitive to variations in parameters associated with
      nutrient factors, photosynthesis and light intensity. The maximum productivity
      and biomass concentration were achieved under mixotrophic nitrogen sufficient
      conditions, while the maximum storage content was obtained under mixotrophic
      nitrogen deficient conditions. 

PMID- 24576923
TI  - Effect of Ramadan fasting on serum concentration of apelin-13 and new obesity
      indices in healthy adult men.
AB  - BACKGROUND: The aim of this study was to determine how Ramadan fasting (RF)
      affected the recently described new obesity indices [visceral adiposity index
      (VAI), waist circumference to height ratio (WHtR), body adiposity index (BAI)],
      and serum concentration of apelin-13 (RF) in healthy adult men. MATERIAL AND
      METHODS: For this purpose, 42 healthy adult men were selected. Anthropometric
      parameters were measured and a sample of venous blood was obtained for
      biochemical assays on the first and last days of Ramadan. When all subjects were
      evaluated, all anthropometric parameters changed except VAI. Serum apelin-13,
      triglyceride (TG), HDL-cholesterol (HDL-C), and insulin levels did not change.
      When patients were divided into 3 groups according to body mass index (BMI), BAI
      decreased in normal-weight subjects and WHtR decreased in other groups, but VAI
      and apelin-13 did not change in any groups. RESULTS: We demonstrate for the first
      time that while some anthropometric parameters changed, VAI and serum apelin-13
      levels did not change with RF. BMI, waist circumference (WC), TG, and HDL-C were
      evaluated together in calculation of VAI. TG, VAI, and HDL-C remained unchanged
      by RF. Even if body weight (BW) and BMI decreased, apelin-13 was not affected by
      RF. The data on serum apelin-13 may have been influenced by the small-percentage
      decrease in BW, as well as insignificant improvements in metabolic parameters
      such as lipid profiles, glucose, and insulin. CONCLUSIONS: We found that Ramadan
      fasting in healthy adult men was associated with significant decreases in BW,
      BMI, WHtR, and BAI, but we found no significant changes in VAI and serum apelin
      13 concentrations.

PMID- 24576924
TI  - Predictors of mortality and progression in scleroderma-associated interstitial
      lung disease: a systematic review.
AB  - BACKGROUND: Interstitial lung disease (ILD) is the leading cause of morbidity and
      mortality in patients with systemic sclerosis (SSc); however, prognostication of
      SSc-associated ILD (SSc-ILD) remains challenging. We conducted a systematic
      review to identify variables that predict mortality and ILD progression in SSc
      ILD. METHODS: Three databases were searched to identify all studies relating to
      predictors of mortality or ILD progression in SSc-ILD. Studies were eligible if
      they were published in English and included >= 10 adults with SSc-ILD. Two
      authors independently reviewed and extracted data from acceptable studies.
      RESULTS: The initial search identified 3,145 unique citations. Twenty-seven
      studies, including six abstracts, met the inclusion criteria. A total of 1,616
      patients with SSc-ILD were included. Patient-specific, ILD-specific, and SSc
      specific variables predicted mortality and progression; however, most predictors
      were identified in only one study. Most studies did not fully account for
      potential confounders, and none of the studies included a validation cohort.
      Older age, lower FVC, and lower diffusing capacity of carbon monoxide predicted
      mortality in more than one study. Male sex, extent of disease on high-resolution
      CT (HRCT) scan, presence of honeycombing, elevated KL-6 values, and increased
      alveolar epithelial permeability were identified as predictors of both mortality
      and ILD progression on unadjusted analysis. The extent of disease on HRCT scan
      was the only variable that independently predicted both mortality and ILD
      progression. CONCLUSIONS: Mortality and ILD progression were predicted by several
      patient-specific, ILD-specific, and SSc-specific factors. Additional prospective
      studies are required to validate these preliminary findings and to identify
      combinations of variables that accurately predict the prognosis of SSc-ILD.

PMID- 24576925
TI  - Peer deviance, parental divorce, and genetic risk in the prediction of drug abuse
      in a nationwide Swedish sample: evidence of environment-environment and gene
      environment interaction.
AB  - IMPORTANCE: Peer deviance (PD) strongly predicts externalizing psychopathologic
      conditions but has not been previously assessable in population cohorts. We
      sought to develop such an index of PD and to clarify its effects on risk of drug
      abuse (DA). OBJECTIVES: To examine how strongly PD increases the risk of DA and
      whether this community-level liability indicator interacts with key DA risk
      factors at the individual and family levels. DESIGN, SETTING, AND PARTICIPANTS:
      Studies of future DA registration in 1,401,698 Swedish probands born from January
      1, 1970, through December 31, 1985, and their adolescent peers in approximately
      9200 small community areas. Peer deviance was defined as the proportion of
      individuals born within 5 years of the proband living in the same small community
      when the proband was 15 years old who eventually were registered for DA. MAIN
      OUTCOMES AND MEASURES: Drug abuse recorded in medical, legal, or pharmacy
      registry records. RESULTS: Peer deviance was associated with future DA in the
      proband, with rates of DA in older and male peers more strongly predictive than
      in younger or female peers. The predictive power of PD was only slightly
      attenuated by adding measures of community deprivation, collective efficacy, or
      family socioeconomic status. Probands whose parents were divorced were more
      sensitive to the pathogenic effects of high PD environments. A robust positive
      interaction was also seen between genetic risk of DA (indexed by rates of DA in
      first-, second-, and third-degree relatives) and PD exposure. CONCLUSIONS AND
      RELEVANCE: With sufficient data, PD can be measured in populations and strongly
      predicts DA. In a nationwide sample, risk factors at the level of the individual
      (genetic vulnerability), family (parental loss), and community (PD) contribute
      substantially to risk of DA. Individuals at elevated DA risk because of parental
      divorce or high genetic liability are more sensitive to the pathogenic effects of
      PD. Although the effect of our PD measure on DA liability cannot be explained by
      standard measures of community or family risk, we cannot, with available data,
      discriminate definitively between the effect of true peer effects and other
      unmeasured risk factors.

PMID- 24576926
TI  - Functional connectivity and temporal variability of brain connections in adults
      with attention deficit/hyperactivity disorder and bipolar disorder.
AB  - OBJECTIVES: To assess brain functional connectivity and variability in adults
      with attention deficit/hyperactivity disorder (ADHD) or euthymic bipolar disorder
      (BD) relative to a control (CT) group. METHODS: Electroencephalography (EEG) was
      measured in 35 participants (BD = 11; ADHD = 9; CT = 15) during an eyes-closed 10
      min rest period, and connectivity and graph theory metrics were computed. A
      coefficient of variation (CV) computed also the connectivity's temporal
      variability of EEG. Multivariate associations between functional connectivity and
      clinical and neuropsychological profiles were evaluated. RESULTS: An enhancement
      of functional connectivity was observed in the ADHD (fronto-occipital
      connections) and BD (diffuse connections) groups. However, compared with CTs,
      intrinsic variability (CV) was enhanced in the ADHD group and reduced in the BD
      group. Graph theory metrics confirmed the existence of several abnormal network
      features in both affected groups. Significant associations of connectivity with
      symptoms were also observed. In the ADHD group, temporal variability of
      functional connections was associated with executive function and memory
      deficits. Depression, hyperactivity and impulsivity levels in the ADHD group were
      associated with abnormal intrinsic connectivity. In the BD group, levels of
      anxiety and depression were related to abnormal frontotemporal connectivity.
      CONCLUSIONS: In the ADHD group, we found that intrinsic variability was
      associated with deficits in cognitive performance and that connectivity
      abnormalities were related to ADHD symptomatology. The BD group exhibited less
      intrinsic variability and more diffuse long-range brain connections, and those
      abnormalities were related to interindividual differences in depression and
      anxiety. These preliminary results are relevant for neurocognitive models of
      abnormal brain connectivity in both disorders.

PMID- 24576927
TI  - MULTIMODAL CLASSIFICATION OF DEMENTIA USING FUNCTIONAL DATA, ANATOMICAL FEATURES
      AND 3D INVARIANT SHAPE DESCRIPTORS.
AB  - Multimodality classification of Alzheimer's disease (AD) and its prodromal stage,
      Mild Cognitive Impairment (MCI), is of interest to the medical community. We
      improve on prior classification frameworks by incorporating multiple features
      from MRI and PET data obtained with multiple radioligands, fluorodeoxyglucose
      (FDG) and Pittsburg compound B (PIB). We also introduce a new MRI feature,
      invariant shape descriptors based on 3D Zernike moments applied to the
      hippocampus region. Classification performance is evaluated on data from 17
      healthy controls (CTR), 22 MCI, and 17 AD subjects. Zernike significantly
      outperforms volume, accuracy (Zernike to volume): CTR/AD (90.7% to 71.6%),
      CTR/MCI (76.2% to 60.0%), MCI/AD (84.3% to 65.5%). Zernike also provides
      comparable and complementary performance to PET. Optimal accuracy is achieved
      when Zernike and PET features are combined (accuracy, specificity, sensitivity),
      CTR/AD (98.8%, 99.5%, 98.1%), CTR/MCI (84.3%, 82.9%, 85.9%) and MCI/AD (93.3%,
      93.6%, 93.3%).

PMID- 24576928
TI  - [Diagnostic criteria for primary osteoporosis : year 2012 revision].
AB  - In 1995, the Japanese Society for Bone and Mineral Metabolism (now the Japanese
      Society for Bone and Mineral Research) established The Osteoporosis Diagnostic
      Criteria Review Committee. Following discussion held at the 13th scientific
      meeting of the Society in 1996, the Committee, with the consensus of its members,
      proposed diagnostic criteria for primary osteoporosis. The Committee revised
      those criteria in 1996 and again in 2000. Japanese Society for Bone and Mineral
      Research and Japan Osteoporosis Society Joint Review Committee for the Revision
      of the Diagnostic Criteria for Primary Osteoporosis aimed at obtaining
      international consistency and made a revised edition based on the new findings in
      2012. 

PMID- 24576929
TI  - [Justification criteria for vertebral fractures ; year 2012 revision].
AB  - Justification Criteria for Vertebral Fractures 2012 version was made based on new
      clinical findings. Major differences in this version compared to the 1996 version
      are 1) inclusion of the semi quantitative method (SQ) , 2) statements to improve
      considerations during radiographic analysis, and 3) the need for more detailed
      evaluation by MRI. New Justification Criteria aims that the treatment of
      vertebral fracture in both fracture and osteoporosis is properly performed in
      daily clinical practice.

PMID- 24576930
TI  - [Criteria for initiation of pharmacological treatment by Japanese 2011 guidelines
      for prevention and treatment of osteoporosis].
AB  - The goals of osteoporosis treatment are prevention of fracture. If the patients
      with higher risk of fragility fractures are treated, the larger effect on
      reduction of the risk of fragility fractures is expected. Criteria for initiating
      pharmacological treatment in U.S.A or Europe are based on cost-effectiveness. In
      Japan, the criteria for initiating pharmacological treatment to prevent fragility
      fracture were established in the revised version of 2011 guidelines for
      prevention and treatment of osteoporosis. In these criteria, postmenopausal women
      and men age 50 and older with vertebral fracture are considered for treatment
      regardless of bone density. FRAX(r) was newly introduced to consider whether or
      not to initiate pharmacological treatment in persons without a fragility fracture
      who have a low bone mass.

PMID- 24576931
TI  - [Update on fracture risk in life style-related diseases].
AB  - Accumulating evidence shows that type 2 diabetes and chronic kidney disease (CKD)
      enhance fracture risk mainly by deteriorating bone quality. Vertebral fracture on
      X-ray films and hip fracture in past history in subjects of 50 years old or more
      are hallmarks to start medication for osteoporosis. Patients with diabetes or CKD
      who have no fracture could undergo drug treatments if their bone mineral density
      is osteopenic, considering the established link between these disorders and
      fracture risk. 

PMID- 24576932
TI  - [Fracture risk associated with drugs other than glucocorticoids].
AB  - Many drugs influence fracture risk besides glucocorticoid, a most common cause of
      drug-induced osteoporosis. It is well established that drugs used for anti-sex
      steroids therapy for breast and prostate cancers increase fracture risk,
      including GnRH agonists, aromatase inhibitors, and anti-androgens. Increased
      fracture risk is also established with anti-diabetic thiazolidinediones by a
      randomized control study as well as meta analysis of observational studies.
      Multiple observational studies have indicated increased fracture risks with
      selective serotonin reuptake inhibitors and proton pump inhibitors. Excess
      thyroid hormones, anti epileptics, heparin, warfarin, may also be associated with
      an increase in fracture risks. On the contrary, statins, thiazides, beta
      blockers, and nitrates may be associated with decreased fracture risks.

PMID- 24576933
TI  - [Clinical usefulness of bone turnover markers with the treatment of
      osteoporosis].
AB  - Bone turnover markers (BTMs) are known the bone formation marker, the bone
      resorption marker and the bone matrix related marker participating in bone
      quality, respectively. In the Guidelines for the Use of Bone Metabolic Markers in
      the Diagnosis and Treatment of Osteoporosis (2012 Edition) from publishing Japan
      Osteoporosis Society Committee, the newly and commonly BTMs were considered to
      give the normal reference value in Japanese people, the reevaluation of MSC, and
      the influence of renal function on BTMs, respectively. The flow chart of the
      measurement of bone resorption markers and bone formation markers when selecting
      drug treatment for osteoporosis, the measurement of ucOC and bone resorption
      markers when selecting drug treatment in osteoporosis, and the evaluation of
      therapeutic effects of bone antiresorption drugs using bone resorption markers
      were corrected newly in the guideline 2012 edition. It is thought that the BTMs
      have been continued more developing as essential biomarker with the treatment of
      osteoporosis in the future. 

PMID- 24576934
TI  - [Prediction by early change of bone metabolic markers of the efficacy of anti
      osteoporotic drugs on bone mass in osteoporotic patients].
AB  - The importance of measurement of bone metabolic markers has been increasingly
      recognized in the treatment of osteoporosis. Bone is a dynamic organ in which
      bone formation and resorption continuously occurs. Biochemical marker for bone
      metabolism is an non-invasive measure to assess bone metabolic state. Although
      the purpose of its measurement was initially hypothesized to predict rate of bone
      loss, the increase of bone marker by itself provides a clinically relevant marker
      for bone fragility. Furthermore, measurement of bone marker is known to help
      improve drug compliance. Recent sophistication of bone marker measurement and the
      increasing kinds of bone markers increase the importance of its measurement to
      improve osteoporosis treatment. 

PMID- 24576935
TI  - [Treatment goals of osteoporosis].
AB  - Decision in starting and modulating the treatment of osteoporosis is being done
      by bone mineral density prevalent fractures, bone turnover markers, and other
      clinical indicators. However, the goal for the treatment of osteoporosis has not
      been established. Currently, treat-to-target is the most urgent issue to be
      discussed in the field of osteoporosis. In this article, the present status of
      this discussion is reviewed. 

PMID- 24576936
TI  - [Prevention of osteoporosis in different life stages and conditions].
AB  - While prevention forms part of the armamentarium for osteoporosis which is no
      less important than treatment, there is as yet a paucity of evidence that
      provides the rationale for prevention compared to that for treatment in
      osteoporosis. While preventive measures against osteoporosis vary depending on
      the life stage of the patient being targeted (i.e., young, perimenopausal or
      elderly) , prevention is being addressed in this article from a different
      perspective with a focus on the following three areas : prevention of onset of
      osteoporosis, prevention of osteoporotic fracture, and prevention of falls. The
      biggest challenge in preventing the onset of osteoporosis has to do with how best
      to alert the patient to the risk of osteoporosis which remains nearly
      asymptomatic, then to encourage her to seek medical consultation, and finally to
      prevent osteoporosis from happening in the patient. Again, while the importance
      of preventing primary osteoporotic fracture is beginning to be widely recognized,
      how to keep a chain reaction of fracture events from happening in osteoporotic
      patients remains a major challenge to be addressed. Lastly, as fracture events go
      hand in hand with falls, how to minimize the impact of falls in such a way that
      they do not lead to fractures remains yet another challenge calling for
      attention. 

PMID- 24576937
TI  - [Anti-osteoporosis drugs based on the guidelines for the Prevention and Treatment
      of Osteoporosis (2011 edition) ].
AB  - The aim of osteoporosis treatment is to reduce fracture risk. Many kinds of anti
      osteoporosis drugs are available in these days, and most of them increase bone
      mineral density and reduce the risk of fractures. Japanese 2011 guidelines for
      prevention and treatment of osteoporosis documents the recommendation level of
      each osteoporosis drugs. It is important to select drugs appropriate for each
      osteoporosis patient considering the mechanisms of drug action and their clinical
      efficiency. 

PMID- 24576938
TI  - [Bisphosphonate-related osteonecrosis of the jaw-after a decade has passed].
AB  - It has been passed 10 years since the first article of bisphosphonate-related
      osteonecrosis of the jaw (BRONJ) was reported in 2003. During this period of
      time, turmoil and confusion initially seen in physicians, dentists and patients
      in the management of BRONJ have been gradually and significantly settling and
      preventive methods for BRONJ have been developed to some extent due to the
      accumulation of substantial amounts of information and clinical experience.
      Further, Japanese version of position paper for BRONJ that suggests unified view
      of the pathophysiology of BRONJ and consistent treatments of BRONJ was published
      in 2010 and 2012. However, the mechanism and pathophysiology of BRONJ still
      remain elusive. The recognition for BRONJ is still inconsistent between
      physicians and dentists. It is also noted that a new anti-resorptive drug
      denosumab is associated with ONJ. Thus, there are still lots to learn and study.
      In this chapter current our understanding of BRONJ will be described. 

PMID- 24576939
TI  - [Current topics over updating guidelines on the management and treatment of
      glucocorticoid-induced osteoporosis].
AB  - Glucocorticoids (GCs) were widely used for the treatment of various disorders.
      Since GC-induced bone loss is most rapid during the initial 3 - 6 months and
      primary prevention of bone loss is especially important, guidelines for
      management of GC-induced osteoporosis have been published overseas and in Japan.
      In response to changes in the circumstances surrounding GIO regarding fracture
      assessment tool and drug therapy, ACR revised recommendations incorporated
      FRAX(r), the WHO fracture risk assessment tool and the Japanese Society of Bone
      and Mineral Research have finished revision work of the guidelines and the
      updated guideline will be published soon. 

PMID- 24576940
TI  - Silver-catalyzed dynamic systemic resolution of alpha-iminonitriles in a 1,3
      dipolar cycloaddition process.
AB  - A dynamic azomethine ylide system was established using Sc(OTf)3 and Ag/Taniaphos
      as catalysts. The system was subsequently kinetically resolved in a tandem 1,3
      dipolar cycloaddition process where the silver complex acted as both a reaction
      catalyst and an external selector, resulting in the formation of an exclusive
      pyrrolidine product in good yield and enantiopurity. 

PMID- 24576943
TI  - Improved electrochemical performance of SnO2-mesoporous carbon hybrid as a
      negative electrode for lithium ion battery applications.
AB  - To utilize the high specific capacity of SnO2 as an anode material in lithium-ion
      batteries, one has to overcome its poor cycling performance and rate capability,
      which result from large volume expansion (~300%) of SnO2 during charging
      discharging cycles. Hence, to accommodate the volume change during cycling, SnO2
      nanoparticles of 6 nm diameter were synthesized specifically only on the outer
      surface of the mesopores, present within mesoporous carbon (CMK-5) particles,
      resulting in an effective buffering layer. To that end, the synthesis process
      first involves the formation of 3.5 nm SnO2 nanoparticles inside the mesopores of
      mesoporous silica (SBA-15), the latter being used as a template subsequently to
      obtain SnO2-CMK-5 hybrid particles. SnO2-CMK-5 exhibits superior rate
      capabilities, e.g. after 30 cycles, a specific discharge capacity of 598 mA h g(
      1), at a current density of 178 mA g(-1). Electrochemical impedance spectroscopy
      reveals that the SnO2-CMK-5 electrode undergoes a significant reduction in solid
      electrolyte interfacial and charge transfer resistances, with a simultaneous
      increase in the diffusion coefficient of lithium ions, all these in comparison to
      an electrode made of only SnO2 nanoparticles. This enhances the potential of
      using the SnO2-CMK-5 hybrid as a negative electrode, in terms of improved
      discharge capacity and cycling stability, compared to other electrodes, such as
      only SnO2 or only CMK-5. 

PMID- 24576942
TI  - Wild fish from the Bay of Quinte Area of Concern contain elevated tissue
      concentrations of PCBs and exhibit evidence of endocrine-related health effects.
AB  - The Bay of Quinte (BOQ) is an Area of Concern listed under the Great Lakes Water
      Quality Agreement. The presence of dioxins and dioxin-like PCBs in fish in the
      BOQ AOC has led to restrictions on fish consumption by humans, which is a
      beneficial use impairment. Adult yellow perch (Perca flavescens) and brown
      bullhead (Ameiurus nebulosus) were sampled from Trenton, Belleville, and
      Deseronto (reference site) in the BOQ. A suite of hormone assays and various
      measures of exposure and/or sublethal health effects were used to assess the
      health status of fish of both species and sex. Condition factor, hepatosomatic
      index, ethoxyresorufin-O-deethylase activity, circulating steroid and thyroid
      hormones, thyroid activation, oocyte size distribution, spermatogenic cell
      stages, and plasma vitellogenin were among the endpoints that were significantly
      (p < 0.05) affected by location. Many of those effects corresponded with
      significantly (p < 0.05) greater tissue concentrations of polychlorinated
      biphenyls (PCBs) at Belleville and Trenton. Hepatic extracts from brown bullhead
      sampled from Trenton had significantly (p < 0.05) greater binding activity to the
      androgen receptor and sex steroid binding protein. Taken together, these data and
      preliminary data from a concomitant study suggest that PCBs are likely being
      hydroxylated in vivo, resulting in enhanced bioactivity at endocrine receptors
      and measurable health responses. The present study supports the growing body of
      evidence that PCBs and their metabolites can affect fish thyroid and steroid
      hormone systems.

PMID- 24576941
TI  - Nanostructured optical photonic crystal biosensor for HIV viral load measurement.
AB  - Detecting and quantifying biomarkers and viruses in biological samples have broad
      applications in early disease diagnosis and treatment monitoring. We have
      demonstrated a label-free optical sensing mechanism using nanostructured photonic
      crystals (PC) to capture and quantify intact viruses (HIV-1) from biologically
      relevant samples. The nanostructured surface of the PC biosensor resonantly
      reflects a narrow wavelength band during illumination with a broadband light
      source. Surface-adsorbed biotarget induces a shift in the resonant Peak
      Wavelength Value (PWV) that is detectable with <10 pm wavelength resolution,
      enabling detection of both biomolecular layers and small number of viruses that
      sparsely populate the transducer surface. We have successfully captured and
      detected HIV-1 in serum and phosphate buffered saline (PBS) samples with viral
      loads ranging from 10(4) to 10(8) copies/mL. The surface density of immobilized
      biomolecular layers used in the sensor functionalization process, including 3
      mercaptopropyltrimethoxysilane (3-MPS), N-gamma-Maleimidobutyryl-oxysuccinimide
      ester (GMBS), NeutrAvidin, anti-gp120, and bovine serum albumin (BSA) were also
      quantified by the PC biosensor.

PMID- 24576945
TI  - Treatment of metastatic melanoma with pazopanib: A report of five patient cases.
AB  - Metastatic melanoma has a median length of survival after diagnosis of 6-9
      months. Unfortunately, the National Comprehensive Cancer Network clinical
      practice guidelines for treating stage IV, unresectable, metastatic melanoma are
      limited with regard to treatment options. Pazopanib (VotrientTM) is FDA-approved
      for advanced soft tissue sarcoma and advanced renal cell carcinoma. Limited
      research exists for using pazopanib in the treatment of metastatic melanoma. We
      present five cases in which pazopanib was used in combination with paclitaxel +/-
      carboplatin for treatment of unresectable, metastatic melanoma. 

PMID- 24576944
TI  - Hemolytic anemia in two patients with glioblastoma multiforme: A possible
      interaction between vorinostat and dapsone.
AB  - Patients undergoing treatment for glioblastoma multiforme are routinely placed on
      prophylactic treatment for Pneumocystis jirovecii pneumonia because of
      significant therapy-induced lymphopenia. In patients with sulfa allergies,
      dapsone prophylaxis is often used due to its efficacy, long half-life, cost
      effectiveness, and general safety at low doses. However, dapsone may uncommonly
      induce a hemolytic anemia, particularly in patients deficient of glucose-6
      phosphate dehydrogenase. This hemolysis is thought to be a result of oxidative
      stress on red blood cells induced by dapsone metabolites which produce reactive
      oxygen species that disrupt the red blood cell membrane and promote splenic
      sequestration. A single case report of dapsone-induced hemolytic anemia in a
      patient with glioblastoma multiforme has been reported. We present two patients
      with glioblastoma multiforme who developed severe hemolytic anemia shortly after
      initiating therapy with vorinostat, a pan-active histone deacetylase inhibitor,
      while on prophylactic dapsone. There are several potential mechanisms by which
      histone deacetylase inhibition may alter dapsone metabolism including changes in
      hepatic acetylation or N-glucuronidation leading to an increase in the
      bioavailability of dapsone's hematotoxic metabolites. In addition, vorinostat may
      lead to increased hemolysis through inhibition of heat shock protein-90, a
      chaperone protein that maintains the integrity of the red blood cell membrane
      cytoskeleton. The potential interaction between dapsone and vorinostat may have
      important clinical implications as more than 10 clinical trials evaluating drug
      combinations with vorinostat in patients with malignant glioma are either ongoing
      or planned in North America. 

PMID- 24576948
TI  - The carbapenemase threat in the animal world: the wrong culprit.

PMID- 24576949
TI  - Candida glabrata drug:H+ antiporter CgTpo3 (ORF CAGL0I10384g): role in azole drug
      resistance and polyamine homeostasis.
AB  - OBJECTIVES: The ability of opportunistic pathogenic Candida species to persist
      and invade specific niches in the human host depends on their resistance to
      natural growth inhibitors and antifungal therapy. This work describes the role of
      the Candida glabrata drug:H(+) antiporter CgTpo3 (ORF CAGL0I10384g) in this
      context. METHODS: Deletion and cloning of CgTPO3 was achieved using molecular
      biology tools. C. glabrata strain susceptibility was assayed based on growth in
      liquid and solid media and through MIC determination. Radiolabelled compound
      accumulation or HPLC were used for the assessment of the role of CgTpo3 as a drug
      or polyamine transporter. Quantitative RT-PCR was used for expression analysis.
      RESULTS: CgTpo3 was found to confer resistance to azole drugs in C. glabrata.
      This protein was found to be localized to the plasma membrane and to decrease the
      intracellular accumulation of [(3)H]clotrimazole, playing a direct role in its
      extrusion from pre-loaded C. glabrata cells. CgTPO3 was further found to confer
      resistance to spermine, complementing the susceptibility phenotypes exhibited by
      the deletion of its Saccharomyces cerevisiae homologue, TPO3. In spermine
      stressed C. glabrata cells, CgTPO3 is transcriptionally activated in a CgPdr1
      dependent manner, contributing to a decrease in the intracellular concentration
      of this polyamine. Clotrimazole exposure was found to lead to the intracellular
      accumulation of spermine, and pre-exposure to this polyamine was found
      consistently to lead to increased clotrimazole resistance. CONCLUSIONS:
      Altogether, these results point to a significant role for CgTpo3 in azole drug
      resistance and in the tolerance to high polyamine concentrations, such as those
      found in the urogenital tract.

PMID- 24576947
TI  - HDL-transferred microRNA-223 regulates ICAM-1 expression in endothelial cells.
AB  - High-density lipoproteins (HDL) have many biological functions, including
      reducing endothelial activation and adhesion molecule expression. We recently
      reported that HDL transport and deliver functional microRNAs (miRNA). Here we
      show that HDL suppresses expression of intercellular adhesion molecule 1 (ICAM-1)
      through the transfer of miR-223 to endothelial cells. After incubation of
      endothelial cells with HDL, mature miR-223 levels are significantly increased in
      endothelial cells and decreased on HDL. However, miR-223 is not transcribed in
      endothelial cells and is not increased in cells treated with HDL from miR-223(-/
      ) mice. HDL inhibit ICAM-1 protein levels, but not in cells pretreated with miR
      223 inhibitors. ICAM-1 is a direct target of HDL-transferred miR-223 and this is
      the first example of an extracellular miRNA regulating gene expression in cells
      where it is not transcribed. Collectively, we demonstrate that HDL's anti
      inflammatory properties are conferred, in part, through HDL-miR-223 delivery and
      translational repression of ICAM-1 in endothelial cells. 

PMID- 24576946
TI  - Role of proteolytic activation of protein kinase Cdelta in the pathogenesis of
      prion disease.
AB  - Prion diseases are infectious and inevitably fatal neurodegenerative diseases
      characterized by prion replication, widespread protein aggregation and spongiform
      degeneration of major brain regions controlling motor function. Oxidative stress
      has been implicated in prion-related neuronal degeneration, but the molecular
      mechanisms underlying prion-induced oxidative damage are not well understood. In
      this study, we evaluated the role of oxidative stress-sensitive, pro-apoptotic
      protein kinase Cdelta (PKCdelta) in prion-induced neuronal cell death using
      cerebellar organotypic slice cultures (COSC) and mouse models of prion diseases.
      We found a significant upregulation of PKCdelta in RML scrapie-infected COSC, as
      evidenced by increased levels of both PKCdelta protein and its mRNA. We also
      found an enhanced regulatory phosphorylation of PKCdelta at its two regulatory
      sites, Thr505 in the activation loop and Tyr311 at the caspase-3 cleavage site.
      The prion infection also induced proteolytic activation of PKCdelta in our COSC
      model. Immunohistochemical analysis of scrapie-infected COSC revealed loss of
      PKCdelta positive Purkinje cells and enhanced astrocyte proliferation. Further
      examination of PKCdelta signaling in the RML scrapie adopted in vivo mouse model
      showed increased proteolytic cleavage and Tyr 311 phosphorylation of the kinase.
      Notably, we observed a delayed onset of scrapie-induced motor symptoms in
      PKCdelta knockout (PKCdelta(-/-)) mice as compared with wild-type (PKCdelta(+/+))
      mice, further substantiating the role of PKCdelta in prion disease. Collectively,
      these data suggest that PKCdelta signaling likely plays a role in the
      neurodegenerative processes associated with prion diseases.

PMID- 24576951
TI  - Synthesis of pharmaceutically relevant 17-alpha-amino steroids using an omega
      transaminase.
AB  - An efficient and sustainable biocatalytic route for the synthesis of important 17
      alpha-amino steroids has been developed using an omega-transaminase variant from
      Arthrobacter sp. Optimisation of the reaction conditions facilitated the
      synthesis of these valuable synthons on a preparative scale, affording excellent
      isolated yields and stereocontrol. 

PMID- 24576950
TI  - Determinants of hepatocellular carcinoma in cirrhotic patients treated with
      nucleos(t)ide analogues for chronic hepatitis B.
AB  - OBJECTIVES: We aimed to identify determinants of hepatocellular carcinoma (HCC)
      in cirrhotic patients who received nucleos(t)ide analogues for chronic hepatitis
      B (CHB). PATIENTS AND METHODS: This retrospective-prospective study screened all
      patients (n = 1630) who received antiviral therapy for CHB between 1 September
      2007 and 31 March 2013 at the E-Da Hospital and enrolled 210 consecutive
      cirrhotic patients with pretreatment viral DNA >2000 IU/mL. Those who developed
      HCC within 3 months of treatment were excluded. All participants were observed
      until occurrence of HCC, death or 1 January 2014. The incidence and determinants
      of HCC were estimated using competing risk analyses adjusted for mortality.
      RESULTS: Thirty-five (16.7%) patients developed HCC during a median follow-up of
      25.2 months (IQR, 16.3-37.3 months), with a cumulative incidence of 24.1% (95%
      CI, 16.3%-32.0%) at 5 years. Multivariate-adjusted analyses identified age >55
      years [adjusted hazard ratio (HR), 2.19; 95% CI, 1.03-4.66], male gender
      (adjusted HR, 3.07; 95% CI, 1.05-9.02), model for end-stage liver disease (MELD)
      score >12 points (adjusted HR, 2.16; 95% CI, 1.10-4.23) and diabetes mellitus
      (DM; adjusted HR, 3.49; 95% CI, 1.54-7.91) as independent risk factors after
      adjusting for multiple covariates, including antidiabetes medication. A scoring
      formula that used information on age, gender, MELD score, DM and antidiabetes
      regimen significantly discriminated patients at high or low risk of HCC, with
      sensitivity and specificity of 82.9% and 62.3%, respectively. CONCLUSIONS: Age,
      gender, hepatic dysfunction, DM and medication for DM are baseline factors that
      stratify the risk of HCC in cirrhotic patients who receive nucleos(t)ide
      analogues for CHB.

PMID- 24576952
TI  - Commentary.

PMID- 24576953
TI  - Optogenetic activation of Gq signalling modulates pacemaker activity of
      cardiomyocytes.
AB  - AIMS: Investigation of Gq signalling with pharmacological agonists of Gq-coupled
      receptors lacks spatio-temporal precision. The aim of this study was to establish
      melanopsin, a light-sensitive Gq-coupled receptor, as a new tool for the
      investigation of spatial and temporal effects of Gq stimulation on pacemaking in
      cardiomyocytes at an early developmental stage. METHODS AND RESULTS: A vector for
      ubiquitous expression of melanopsin was tested in HEK293FT cells, which showed
      light-induced production of inositol-1,4,5-trisphosphate and elevation of
      intracellular Ca(2+) concentration. Mouse embryonic stem cells were stably
      transfected with this plasmid and differentiated into spontaneously beating
      embryoid bodies (EBs). Cardiomyocytes within EBs showed melanopsin expression and
      illumination (60 s, 308.5 nW/mm(2), 470 nm) of EBs increased beating rate within
      10.2 +/- 1.7 s to 317.1 +/- 16.3% of baseline frequency. Illumination as short as
      5 s was sufficient for generating the maximal frequency response. After
      termination of illumination, baseline frequency was reached with a decay constant
      of 27.1 +/- 2.5 s. The light-induced acceleration of beating frequency showed a
      sigmoid dependence on light intensity with a half maximal effective light
      intensity of 41.7 nW/mm(2). Interestingly, EBs showed a high rate of irregular
      contractions after termination of high-intensity illumination. Local Gq
      activation by illumination of a small region in a functional syncytium of
      cardiomyocytes led to pacemaker activity within the illuminated area.
      CONCLUSIONS: Light-induced Gq activation in melanopsin-expressing cardiomyocytes
      increases beating rate and generates local pacemaker activity. We propose that
      melanopsin is a powerful optogenetic tool for the investigation of spatial and
      temporal aspects of Gq signalling in cardiovascular research.

PMID- 24576955
TI  - Interaction between myofibroblasts and stem cells in the fibrotic heart:
      balancing between deterioration and regeneration.
AB  - Signalling between the various cell types in the heart has been investigated for
      decades. However, relatively little is known about the interplay between the
      cardiac fibroblasts and myofibroblasts, which help to maintain myocardial tissue
      structure and function, and resident cardiac or extracardiac stem cells involved
      in tissue homeostasis and repair. Much of our knowledge about these interactions
      is derived from experimental animal models, especially those of myocardial
      infarction and stem cell transplantation. However, it still remains incompletely
      understood how stem cell therapy could modulate cardiac fibrosis in a beneficial
      manner and, how on the other hand, fibrotic processes in the heart may affect the
      therapeutic potential of stem cell therapy. A detailed and mechanistic insight
      into these matters would expedite the therapeutic optimization of cardiac cell
      therapy for the fibrotic heart and may even provide a basis for future biological
      therapies aiming for a reversal of cardiac fibrosis. Therefore, the main focus of
      this review is to discuss interactions between myofibroblasts and stem cells,
      especially in the adult and diseased, fibrotic myocardium, and emphasize those
      aspects that require more investigation using dedicated models and tools. 

PMID- 24576954
TI  - MicroRNA-125b protects against myocardial ischaemia/reperfusion injury via
      targeting p53-mediated apoptotic signalling and TRAF6.
AB  - AIMS: The present study examined the role of microRNA-125b (miR-125b) in
      myocardial ischaemia/reperfusion (I/R) injury. We constructed lentivirus
      expressing miR-125b (LmiR-125b) and developed transgenic mice with overexpression
      of miR-125b. METHODS AND RESULTS: LmiR-125b was transfected into mouse hearts
      through the right common carotid artery. Lentivirus vector (LmiR-Con) served as
      vector control. Untreated mice served as I/R control. Sham operation served as
      sham control. Seven days after transfection, the hearts were subjected to
      ischaemia (45 min) followed by reperfusion (4 h). Myocardial infarct size was
      analysed by 2,3,5-triphenyltetrazolium chloride staining. In separate
      experiments, hearts were subjected to ischaemia (45 min) followed by reperfusion
      for up to 7 days. Cardiac function was measured by echocardiography before, as
      well as 3 and 7 days after myocardial I/R. Increased expression of miR-125b
      significantly decreased I/R-induced myocardial infarct size by 60% and prevented
      I/R-induced decreases in ejection fraction (EF%) and fractional shortening (%FS).
      Transgenic mice with overexpression of miR-125b also showed the protection
      against myocardial I/R injury. Increased expression of miR-125b attenuated I/R
      induced myocardial apoptosis and caspase-3/7 and -8 activities. Western blot
      showed that increased expression of miR-125b suppresses p53 and Bak1 expression
      in the myocardium. In addition, transfection of LmiR-125b decreased the levels of
      TNF receptor-associated factor 6 (TRAF6) and prevented I/R-induced NF-kappaB
      activation. CONCLUSION: miR-125 protects the myocardium from I/R injury by
      preventing p53-mediated apoptotic signalling and suppressing TRAF6-mediated NF
      kappaB activation.

PMID- 24576957
TI  - Isovanillin derived N-(un)substituted hydroxylamines possessing an ortho-allylic
      group: valuable precursors to bioactive N-heterocycles.
AB  - The intramolecular 1,3-dipolar cycloaddition of isovanillin derived N-aryl
      hydroxylamines possessing ortho-allylic dipolarophiles affords novel benzo
      analogues of tricyclic isoxazolidines that can be readily transformed into
      functionalized lactams, gamma-aminoalcohols and oxazepines. The corresponding N
      unsubstituted hydroxylamines give rise to tetrahydroisoquinolines. Anxiogenic
      properties of these compounds are tested in zebra fish. 

PMID- 24576956
TI  - Multi-targeted inhibition of tumor growth and lung metastasis by redox-sensitive
      shell crosslinked micelles loading disulfiram.
AB  - Metastasis, the main cause of cancer related deaths, remains the greatest
      challenge in cancer treatment. Disulfiram (DSF), which has multi-targeted anti
      tumor activity, was encapsulated into redox-sensitive shell crosslinked micelles
      to achieve intracellular targeted delivery and finally inhibit tumor growth and
      metastasis. The crosslinked micelles demonstrated good stability in circulation
      and specifically released DSF under a reductive environment that mimicked the
      intracellular conditions of tumor cells. As a result, the DSF-loaded redox
      sensitive shell crosslinked micelles (DCMs) dramatically inhibited cell
      proliferation, induced cell apoptosis and suppressed cell invasion, as well as
      impairing tube formation of HMEC-1 cells. In addition, the DCMs could accumulate
      in tumor tissue and stay there for a long time, thereby causing significant
      inhibition of 4T1 tumor growth and marked prevention in lung metastasis of 4T1
      tumors. These results suggested that DCMs could be a promising delivery system in
      inhibiting the growth and metastasis of breast cancer. 

PMID- 24576958
TI  - [Comparative study of osteoplastic materials based on chitosan, alginate or
      fibrin with tricalcium phosphate].
AB  - The study presents comparative analysis of porous composites made of chitosan,
      alginate, fibrin with beta-tricalcium phosphate. Histological findings on Wistar
      rat condyles showed that fibrin-beta-TCP-based composite had the most effective
      positive biological response. 

PMID- 24576959
TI  - [Dentin surface morphology changes after applying pastes with calcium
      hydroxyapatite or nanohydroxyapatite].
AB  - This study presents the results of an experimental use of pastes with
      hydroxyapatite and with nanohydroxyapatite to compare the effect of occlusion of
      dentinal tubules. When performing work we estimated the morphological changes of
      the dentin surface using scanning electron and atomic force microscopy. The
      detailed assessment of dentin structural features under significant amplification
      it was possible to identify differences in plugging dentin tubules by different
      kinds of pastes. It was found that the cut surface of dentin after the
      application of the pastes is covered with the unified layer of the paste's
      particles and their individual conglomerates. 

PMID- 24576960
TI  - [Serum, oral and gingival fluid levels of heat shock protein-70, cytokines and
      their autoantibodies by periodontal disease].
AB  - The study of 25 patients with periodontitis showed that the level of heat shock
      protein-70 (HSP70) and IL-1Beta, IL-8 was increased in serum, buccal and gingival
      fluids as compared with healthy individuals, as well as the serum level of IgG
      autoantibodies both to HSP70 and to cytokines. In oral and gingival fluids sIgA
      autoantibodies to the same antigens were found. It was suggested that these
      autoantibodies can eliminate HSP-70 pro-inflammatory cytokines, thus regulating
      their levels in the inflammation area. 

PMID- 24576961
TI  - [Tooth decay complications incidence].
AB  - The aim of the article is to assess the quality of endodontic therapy and
      estimate further treatment needs. 900 orthopantomograms of 442 men and 458 women
      (aged 18-70) without any clinical manifestations of endodontic pathology were
      examined for endodontic treatment. 1,170 patients (41%) had additional intraoral
      radiographs taken for assessment of their periapical status. 2,852 (13.8%) of the
      20,724 teeth examined had periapical lesions and/or root fillings. 2,503 of the
      2,853 teeth were endodontically treated, only 1,011 of them (40.4%) having all
      their root canals obturated. 612 (41.3%) of the 1,492 (59.6%) teeth with
      inadequate root canal fillings hat a healthy apical periodontium. Of the 1,229
      teeth to be endodontically treated 349 teeth required primary treatment, 880
      required retreatment. 

PMID- 24576962
TI  - [Tooth decay and its complication prognosis in smokers].
AB  - The study focuses on complicated and non-complicated tooth decay course and
      prognosis in smokers. Oral status, prevention and treatment effectiveness was
      assessed in 330 non-smokers and 345 smoking patients. The results allowed
      concluding with guidelines for tooth decay prevention and treatment in smokers. 

PMID- 24576963
TI  - [Peace-time gunshot maxillofacial injury in Arkhangelsk region].
AB  - We analyzed civilian gunshot wounds of maxillofacial area in 87 patients living
      in the Arkhangelsk region. It is noted that gunshot injuries most often occur as
      a result of the attempted suicide (45 cases (51,7%)), firearm associated crimes
      (33 cases (37,9%)) and careless handling with the weapon (9 cases (10,4%)). The
      most common wound canal features are described. In the majority of cases
      tangential gunshot wounds were seen (55 cases (63,2%)), penetrating wounds (19
      cases (21,8%)) and perforating wounds (13 cases (15)). During the last years
      increased the number of gunshot injures by traumatic weapons (11 (12.6%)). It is
      recommended to take into consideration the direction and topography of the wound
      canals during the debridement. 

PMID- 24576964
TI  - [Surgical treatment of mandible fractures in heavy drinkers].
AB  - The number of alcohol abusing patients with maxillofacial trauma hospitalised in
      reanimation department or specialized departments is constantly growing and was
      estimated as 36% in the current study. Patients with acute or chronic alcohol
      intoxication and fractures of the lower jaw have problems with fracture fixation.
      Traditional surgical fixation methods are traumatic and not always effective. The
      study evaluates the efficiency of new surgical methods of mandible fractures
      fixation in patients with chronic or acute alcohol intoxication. 

PMID- 24576965
TI  - [Ki-67 and claudin-1 expression in hyperplasia, oral squamous inthraepithelial
      neoplasia and oral squamous cell carcinoma].
AB  - The correlation was investigated between the level of cell proliferation and the
      intensity of claudin-1 expression in oral hyperplasia, squamous intraepithelial
      neoplasia (SIN) and squamous cell carcinoma. Claudin-1 expression and cell
      proliferation were assessed using immunohistochemistry in different epithelial
      layers of oral mucosa. The inverse correlation was revealed between the level of
      cell proliferation and the intensity of claudin-1 expression in oral hyperplasia,
      SIN and squamous cell carcinoma. 

PMID- 24576966
TI  - [Psychological status assessment in patients with TMJ malfunctions].
AB  - This article describes the assessment of psychological status and quality of life
      in 41 patients with temporomandibular joint (TMJ) dysfunction as well as the
      importance of the disease for patients. The study revealed a number of personal
      characteristics and emotional problems in TMJ dysfunction patients, such as
      increased anxiety and low level of psychological stability. 

PMID- 24576967
TI  - [Prospects for the use of nanomaterials and high technology in dentistry. Part
      1].
AB  - The paper presents the possibility of using biologically inert nanomaterials and
      high technology in prosthetic dentistry. Protective coating of nanostructured
      titanium VT1-00 magnetic elements of the locking system of removable dentures
      provides durability and biological inertness and high quality aesthetic design.
      In assessing the microstructure of titanium protective coating of ferromagnetic
      elements and samarium-cobalt magnets found that the nanocrystalline coating is
      formed, resistant to external influences, can significantly improve strength,
      technical and biological characteristics of samarium-cobalt magnets and
      ferromagnetic alloys. Fifteen patients were manufactured dentures with magnetic
      locks. The analysis of performance evaluation prosthetic treatment of patients
      with the use of the proposed prosthetic shows that the majority of patients
      (86.6%) obtained a good result. Patients registered restoration of aesthetic
      standards and the basic functions of dentition. 

PMID- 24576968
TI  - [Periodontal status in children with various morphological forms of chronic
      gastritis and duodenitis].
AB  - The purpose of the study was to determine the condition of the periodontal
      tissues in 80 children with various morphological forms of gastritis and
      duodenitis. The examination included determination of oral hygiene and
      periodontal status by the simplified Green-Vermillion index, Silness-Low index,
      papillary-marginal-alveolar index, gingival Muhlemann-Cowell bleeding index,
      Schiller-Pisarev iodine index. In children with chronic gastritis and duodenitis
      high incidence of chronic catarrhal gingivitis (85.0%) was revealed. At the same
      time it was pointed out that inflammation in the periodontal tissues correlated
      with changes in the gastroduodenal mucosa. In 65.4% of children with superficial
      gastritis and duodenitis, chronic catarrhal gingivitis (localized in 38.5% of
      cases, generalized in 26.9%) was observed. In 94.4% of all children with diffuse
      and erosive gastritis and duodenitis, chronic generalized catarrhal gingivitis
      was observed, and low oral hygiene level was revealed. The severity and duration
      of the underlying disease aggravated clinical manifestations of chronic catarrhal
      gingivitis in children with lesions of the upper gastrointestinal tract. 

PMID- 24576969
TI  - [Clinical and immunological assessment of Polyoxidonium and Tantum Verde
      efficiency by catarrhal gingivitis treatment in children with chronic
      gastroduodenitis].
AB  - The article presents findings allowing estimating effect of local application of
      polioxidonium and yantum verde in 101 children aged 12-17 with chronic catarrhal
      gingivitis and chronic gastroduodenitis. Statistically significant PMA index
      decrease (40.1+/-2.3% till 1.4+/-0.6% (r<0,001)) proved the above mentioned
      therapy scheme to be highly effective for treatment of chronic catarrhal
      gingivitis in children with chronic gastroduodenitis.

PMID- 24576970
TI  - [Prosthetic rehabilitation in patient with forced class III malocclusion].
AB  - The paper presents clinical case of 63 years old edentulous patient with slight
      class III malocclusion. For 15 years he was using inadequately fabricated
      dentures causing forced severe class III malocclusion. Forced progeny was
      corrected by newly fabricated dentures which restored normal orofacial function
      and facial harmony. 

PMID- 24576971
TI  - [Restorative dentist labor efforts and contents structure assessed by time
      study].

PMID- 24576973
TI  - Septal flash predicts cardiac resynchronization therapy response in patients with
      permanent atrial fibrillation.
AB  - AIMS: Patients with heart failure (HF) as well as atrial fibrillation (AF) have
      suboptimal response to cardiac resynchronization therapy (CRT). Identification of
      mechanical abnormalities, amenable to correction with CRT, might improve the
      selection of candidates and CRT efficiency. We evaluated whether abnormal septal
      motion, assessed by the presence of septal flash (SF) is related to CRT response
      in patients with AF. METHODS AND RESULTS: Ninety-four CRT patients with AF were
      included. Echocardiography was performed in all subjects at baseline and at 12
      month follow-up. Abnormal septal motion was defined by the presence of SF (early
      septal inward/outward motion within the isovolumic contraction period/QRS
      duration). Response to CRT was defined as a reduction (>15%) of the end-systolic
      volume of the left ventricle (LV). Univariate and multivariate analyses were
      performed to identify the predictors of CRT response. The mean age was 69 +/- 8
      years, 79% were males, and 59% of patients responded to CRT. Cardiovascular death
      was 14.4% and all-cause mortality was 16.5% during follow-up. Patients with SF at
      baseline that was acutely corrected by CRT were significantly more likely to
      respond than patients without SF. Baseline SF was an independent predictor of CRT
      response (OR 5.24; 95% CI 1.95-14.11). CONCLUSION: Abnormal septal motion,
      assessed by the presence of SF, is a mechanism amenable to CRT correction. Its
      correction is associated with a higher likelihood of CRT response in HF patients
      with long-standing AF. This could improve the selection of candidates to CRT in a
      subgroup with particularly poor response and long-term prognosis.

PMID- 24576975
TI  - Modified criteria for the systemic inflammatory response syndrome improves their
      utility following cardiac surgery.
AB  - BACKGROUND: Debate remains regarding whether the systemic inflammatory response
      syndrome (SIRS) identifies patients with clinically important inflammation.
      Defining criteria may be disproportionately sensitive and lack specificity. We
      investigated the incidence and evolution of SIRS in a homogenous population
      (following cardiac surgery) over 7 days to establish the relationship between
      SIRS and outcome, modeling alternative permutations of the criteria to increase
      their discriminatory power for mortality, length of stay, and organ dysfunction.
      METHODS: We conducted a retrospective analysis of prospectively collected data
      from a cardiothoracic ICU. Consecutive patients requiring ICU admission for the
      first time after cardiac surgery (N = 2,764) admitted over a 41-month period were
      studied. RESULTS: Concurrently, 96.2% of patients met the standard two criterion
      definition for SIRS within 24 h of ICU admission. Their mortality was 2.78%. By
      contrast, three or four criteria were more discriminatory of patients with higher
      mortality (4.21% and 10.2%, respectively). A test dataset suggested that meeting
      two criteria for at least 6 consecutive h may be the best model. This had a
      positive and negative predictive value of 7% and 99.5%, respectively, in a
      validation dataset. It performed well at predicting organ dysfunction and
      prolonged ICU admission. CONCLUSIONS: The concept of SIRS remains valid following
      cardiac surgery. With suitable modification, its specificity can be improved
      significantly. We propose that meeting two or more defining criteria for 6 h
      could be used to define better populations with more difficult clinical courses
      following cardiac surgery. This group may merit a different clinical approach.

PMID- 24576974
TI  - Assessment of plasma C-reactive protein as a biomarker of posttraumatic stress
      disorder risk.
AB  - IMPORTANCE: Posttraumatic stress disorder (PTSD) has been associated in cross
      sectional studies with peripheral inflammation. It is not known whether this
      observed association is the result of PTSD predisposing to inflammation (as
      sometimes postulated) or to inflammation predisposing to PTSD. OBJECTIVE: To
      determine whether plasma concentration of the inflammatory marker C-reactive
      protein (CRP) helps predict PTSD symptoms. DESIGN, SETTING, AND PARTICIPANTS: The
      Marine Resiliency Study, a prospective study of approximately 2600 war zone
      deployed Marines, evaluated PTSD symptoms and various physiological and
      psychological parameters before deployment and at approximately 3 and 6 months
      following a 7-month deployment. Participants were recruited from 4 all-male
      infantry battalions imminently deploying to a war zone. Participation was
      requested of 2978 individuals; 2610 people (87.6%) consented and 2555 (85.8%)
      were included in the present analysis. Postdeployment data on combat-related
      trauma were included for 2208 participants (86.4% of the 2555 included) and on
      PTSD symptoms at 3 and 6 months after deployment for 1861 (72.8%) and 1617
      (63.3%) participants, respectively. MAIN OUTCOMES AND MEASURES: Severity of PTSD
      symptoms 3 months after deployment assessed by the Clinician-Administered PTSD
      Scale (CAPS). RESULTS: We determined the effects of baseline plasma CRP
      concentration on postdeployment CAPS using zero-inflated negative binomial
      regression (ZINBR), a procedure designed for distributions, such as CAPS in this
      study, that have an excess of zeroes in addition to being positively skewed.
      Adjusting for the baseline CAPS score, trauma exposure, and other relevant
      covariates, we found baseline plasma CRP concentration to be a highly significant
      overall predictor of postdeployment CAPS scores (P = .002): each 10-fold
      increment in CRP concentration was associated with an odds ratio of nonzero
      outcome (presence vs absence of any PTSD symptoms) of 1.51 (95% CI, 1.15-1.97; P
      = .003) and a fold increase in outcome with a nonzero value (extent of symptoms
      when present) of 1.06 (95% CI, 0.99-1.14; P = .09). CONCLUSIONS: AND RELEVANCE A
      marker of peripheral inflammation, plasma CRP may be prospectively associated
      with PTSD symptom emergence, suggesting that inflammation may predispose to PTSD.

PMID- 24576978
TI  - Retroperitoneal laparoscopic extravascular stent placement for renal nutcracker
      syndrome: initial experience.
AB  - OBJECTIVE: To report our initial experience in treating renal nutcracker syndrome
      by retroperitoneal laparoscopic extravascular stenting. PATIENTS AND METHODS: Two
      male patients, aged 13 and 16 years, were diagnosed with nutcracker syndrome and
      received retroperitoneal laparoscopic extravascular stent placement. The
      perioperative data were collected and evaluated. The follow-up was 10 and 18
      months. RESULTS: Both procedures were successful without obvious complications.
      Total operative time was 65 and 50 min, estimated blood loss was 110 and 70 ml,
      and postoperative hospital stay was 4 and 6 days. The symptom of gross hematuria
      ceased 3 and 6 days after surgery. Both patients had normal findings during
      follow-up. CONCLUSIONS: Treatment of nutcracker syndrome by retroperitoneal
      laparoscopic extravascular stent placement is a safe and feasible procedure,
      especially for youngsters in the period of physical development. Longer follow-up
      and further experience are needed to evaluate the efficacy of this procedure.

PMID- 24576976
TI  - Genetic variations within metalloproteinases impact on the prophylaxis of
      depressive phases in bipolar patients.
AB  - BACKGROUND: The genetic background of the antidepressant response to
      pharmacological treatment in bipolar disorder (BD) remains elusive. This issue is
      of primary relevance in that the depressive phases of BD are difficult to treat
      and they are associated with suicide. AIM: We investigated the role of a set of
      genetic variations (single-nucleotide polymorphisms) harbored by matrix
      metalloproteinases (MMPs) as predictors of response to treatment in depressed BD
      patients. METHODS: 654 BD patients from the publicly available Systematic
      Treatment Enhancement Program for Bipolar Disorder study were investigated. The
      outcome was the number of depressive events corrected by the number of times
      patients were assessed. Clinical and sociodemographic variables were tested as
      possible stratification factors and included in the analysis if necessary.
      Genetic predictors were 43 SNPs harbored by 17 MMPs. Imputation, quality check
      and pruning were conducted according to standards. RESULTS were corrected for
      multitesting. RESULTS: rs486055 (MMP-10) was associated with the outcome. TT
      homozygotes had 5.08 +/- 3.51 events, CT had 3.47 +/- 3.18 and CC had 2.57 +/-
      2.96 depressive events corrected for the times they had been assessed. The time
      during which BD patients were observed was not significantly different between
      the rs486055 genotypes. We found evidence that MMP-10 may be a mediator of the
      number of depressive phases during BD. Due to the limits of the study including
      the small-to-medium sample size, the naturalistic design and the possible
      occurrence of false-positive findings, independent analyses are warranted.

PMID- 24576979
TI  - Bioconversion of wastewater from sweet potato starch production to Paenibacillus
      polymyxa biofertilizer for tea plants.
AB  - Wastewater from the sweet potato starch industry is a large source of nutrient
      rich substrates. We assessed whether this wastewater could be used to produce
      Paenibacillus polymyxa biofertilizer for foliar application to tea trees. Using
      the central composite design methods we experientially determined that the
      optimal culture conditions for P. polymyxa were pH, 6.5; temperature, 29.0 
      degrees C; and incubation time, 16 h. Under these conditions, a maximum biomass
      of 9.7 * 10(9) cfu/mL was achieved. We then conducted a yearlong field
      investigation to determine the effect of P. polymyxa biofertilizer on the growth
      of tea plants (Camellia sinensis). Tea yield, quantity of water extract, and tea
      polyphenol levels were significantly higher after foliar application of the
      biofertilizer compared to that in the controls by an average of 16.7%, 6.3%, and
      10.4%, respectively. This approach appears to be technically feasible for organic
      tea production, and is an environmentally friendly way to utilize wastewater.

PMID- 24576980
TI  - Prognostic improvement by multidisciplinary therapy in patients with critical
      limb ischemia.
AB  - Although limb salvage rate has improved in critical limb ischemia (CLI), an
      improvement in CLI prognosis has been scarcely reported. Multidisciplinary
      therapy (MT) including revascularization, wound bed preparation, treatment of
      comorbidity, and education of patients with CLI may improve prognosis. The aim of
      this study was to investigate the effectiveness of MT in prognostic improvement.
      We retrospectively analyzed 72 patients with CLI and assessed whether MT improved
      prognosis. The incidence of amputation-free survival (freedom from major
      amputation [MA] and death) was significantly different between the MT and
      conventional groups at 2 years (0% vs 33%; P = .024). After multivariate
      analysis, transfusion (hazard ratio [HR] 5.778; 95% confidence interval [CI],
      2.372-14.073; P < .001), multivessel coronary disease (HR 3.353; 95% CI, 1.309
      8.590; P = .012), and C-reactive protein >5 mg/dL (HR 3.958; 95% CI, 1.359
      11.531; P = .012) were independent predictors for MA or death. We concluded that
      MT was effective in improved mortality and limb salvage rate. 

PMID- 24576981
TI  - Takotsubo cardiomyopathy and acute infectious diseases: a mini-review of case
      reports.
AB  - Takotsubo cardiomyopathy (TTC), also defined as "stress cardiomyopathy," is
      characterized by a systolic dysfunction localized in the apical and medial left
      ventricles. Takotsubo cardiomyopathy is more prevalent in females and it is
      usually related to an event triggered by physical or emotional stress. We
      systematically explored PubMed and Embase medical information source to identify
      case reports showing association between infection and TTC. For each kind of
      infection, we collected a set of data, including pathogen, site of infection,
      clinical outcome, patient age and sex, and author and year of publication. We
      found 26 articles dealing with 27 case reports (74% women). The mean age was 61.4
      +/- 13.7 years and bacterial infections were more frequent (n = 23, 85.2%). In 14
      cases, there was a culture-based definition of the bacterial strain: gram+ in 8
      cases (57.1%) and gram- in 6 cases (42.9%). Clinical outcome was always
      favorable. 

PMID- 24576982
TI  - Acute cardiotoxic effects of adjuvant trastuzumab treatment and its relation to
      oxidative stress.
AB  - Our aim was to evaluate the acute cardiac toxicity of adjuvant trastuzumab
      treatment and its possible relation to changes in oxidative stress.
      Electrocardiographic and echocardiographic tissue Doppler imaging (TDI)
      parameters, activity of antioxidant enzymes (superoxide dismutase; SOD), and
      products of oxidative stress (malondialdehyde; MDA) were analyzed in 30 patients
      with early-stage breast cancer who had adjuvant trastuzumab treatment. There was
      a significant prolongation of QT interval after trastuzumab treatment. There was
      also a significant decrease in left ventricular ejection fraction (LVEF), TDI
      derived S' parameters, and SOD enzyme activity and increase in MDA levels after
      trastuzumab infusion. There was a positive correlation between changes in SOD
      activity and LVEF and a negative correlation between changes in MDA levels and
      LVEF. This study demonstrated a correlation between decreases in LVEF and
      increases in products of the oxidative stress in patients who had adjuvant
      trastuzumab treatment. 

PMID- 24576983
TI  - Carotid intimal thickness and plaque predict prevalence and severity of coronary
      atherosclerosis: a pilot study.
AB  - We determined whether increased carotid intima-media thickness (cIMT) and
      prevalence of carotid plaque (CP) are predictive of prevalence and severity of
      coronary atherosclerosis. Consecutive patients (n = 150) with no history of
      coronary artery disease (CAD), who underwent both carotid ultrasound and computed
      tomographic coronary angiography, were included in the analysis. The mean cIMT
      was higher in patients with CAD than in those without CAD (0.76 vs 0.66 mm, P <
      .003). In a logistic regression analysis, diabetes (P = .03) and CP (P = .02)
      were associated with significant coronary plaque. Backward selection analysis
      (after removing nonsignificant variables) showed higher mean cIMT measurement
      correlated well with prevalence of any coronary plaque (P = .03) and obstructive
      coronary plaque disease (P = .05), whereas presence of CP was a good predictor of
      both obstructive (>50% stenosis P = .003) and any coronary plaque (P = .003). In
      conclusion, CP and cIMT can be useful predictors of prevalence of CAD and its
      severity. 

PMID- 24576984
TI  - Cardiovascular complications in diabetic patients undergoing regular
      hemodialysis: a 5-year observational study.
AB  - We aimed to study the vascular outcomes in hemodialysis (HD) patients based on
      their diabetic status. A cohort observational study was conducted among patients
      undergoing regular HD with a 5-year follow-up. Of the 252 consecutive HD
      patients, 60% were diabetic. Compared with nondiabetics, diabetics were 11 years
      older, 4 years lesser on HD, and more likely to have prior cerebrovascular and
      coronary artery disease (CAD). Overall 5-year follow-up showed that diabetic
      patients had higher rates of HD vascular accesses (57% vs 41%, P = .01), CAD (64%
      vs 33%, P = .001), major amputations (8.6% vs 0%, P = .003), and mortality (66%
      vs 23%, P = .001). On multivariate analysis, independent predictors of mortality
      included number of vascular accesses in nondiabetics and HD duration, CAD, and
      peripheral artery disease in diabetic patients. Diabetes mellitus is associated
      with a significant vascular burden and mortality among HD patients. Moreover, our
      finding highlights the vascular impact of renal failure and HD. 

PMID- 24576985
TI  - Response to the letter to the editor "Can statins alter coronary plaque
      morphology assessed by intravascular ultrasound?".

PMID- 24576986
TI  - Adiponectin as an independent predictor of left ventricular hypertrophy in
      nondiabetic patients with hypertension.
AB  - We evaluated novel and traditional biomarkers as well as hemodynamic parameters
      associated with the development of left ventricular hypertrophy (LVH) in
      nondiabetic patients with hypertension. Nondiabetic patients with hypertension (n
      = 86) were evaluated for lipids, glucose, insulin, homeostasis model assessment
      insulin resistance (HOMA-IR), adiponectin, aldosterone, renin, matrix
      metalloproteinase 2, and endothelin. Arterial elasticity was evaluated using
      pulse wave contour. The LVH parameters were assessed echographically. Adiponectin
      was significantly and inversely associated with left ventricular mass (LVM; P =
      .032). The aldosterone-renin ratio (ARR) was significantly, positively associated
      with LVM (P = .031). Fasting insulin as well as HOMA-IR was significantly,
      positively associated with LVM (P = .036 and P = .025, respectively). In multiple
      linear regression analysis, adiponectin and ARR remained a significant predictor
      of LVM. The present study found that adiponectin and ARR are important
      independent determinants of LVH in nondiabetic patients with hypertension. 

PMID- 24576987
TI  - Varenicline-induced acute dystonic reaction: a case report.
AB  - Dystonia is a syndrome characterized by sustained muscle contractions frequently
      causing twisting and repetitive movements or abnormal postures. Dystonic
      reactions may be a complication of many drugs such as antipsychotics, anti
      emetics and antidepressants. This report presents a 25-year-old patient who was
      admitted to an emergency department with acute dystonia following the use of
      varenicline, a pharmacological agent used for the treatment of nicotine
      addiction. Dystonic reactions may be related to the dopaminergic deficiency
      caused by the use of varenicline. In conclusion, this report suggests that
      varenicline can cause dystonic reaction in at least some patients. 

PMID- 24576988
TI  - Acute psychosis in a verified Huntington disease gene carrier with subtle motor
      signs: psychiatric criteria should be considered for the diagnosis.
AB  - Huntington disease (HD) is an inherited, progressive, autosomal dominant
      disorder. Some patients develop severe chorea or cognitive symptoms. The genetic
      defect causes progressive atrophy of the striatum, the cortex and extrastriatal
      structures (Sheperd GM. Corticostriatal connectivity and its role in disease. Nat
      Rev Neurosci 2013;14:278-91). The precise timing of clinical diagnosis of HD is
      poorly characterized and is mainly based on motor symptoms (Huntington, Study and
      Group. Unified Huntington's Disease Rating Scale: reliability and consistency.
      Huntington Study Group. Mov Discord 1996:136-42). Patients suffering from HD
      frequently show cognitive or affective symptoms even before manifesting motor
      signs. Psychiatric symptoms like depression, apathy, aggression, and
      disinhibition are common, and suicide rates are over four times higher than in
      the general population (Di Maio L, Squitieri F, Napolitano G, Campanella G,
      Trofatter JA, Conneally PM. Suicide risk in Huntington's disease. J Med Genet
      1993;30:293-5). This case report of a female patient with genetically proven HD
      is of special interest because motor or cognitive impairment were absent whereas
      she suffered from symptoms of an acute and severe psychosis likely to be
      symptomatic signs of HD. 

PMID- 24576989
TI  - Influence of metal-support interaction on the surface structure of gold
      nanoclusters deposited on native SiO(x)/Si substrates.
AB  - The structure of small gold nanoclusters (around 2.5 nm) deposited on different
      silica-on-silicon (SiOx/Si) substrates is investigated using several
      characterization techniques (AFM, XRD, EXAFS and GISAXS). The grain morphology
      and the surface roughness of the deposited gold cluster layers are determined by
      AFM. The in-plane GISAXS intensity is modelled in order to obtain information
      about the cluster size and the characteristic length scale of the surface
      roughness. The surface morphology of the deposited clusters depends on whether
      the native defect-rich (n-SiOx/Si) or the defect-poor substrate obtained by
      thermal treatment (t-SiO2/Si) is used. Gold clusters show a stronger tendency to
      aggregate when deposited on n-SiOx/Si, resulting in films characterized by a
      larger grain dimension (around 20 nm) and by a higher surface roughness (up to 5
      nm). The more noticeable cluster aggregation on n-SiOx/Si substrates is explained
      in terms of metal-support interaction mediated by the defects located on the
      surface of the native silica substrate. Evidence of metal-support interaction is
      provided by EXAFS, demonstrating the existence of an Au-O distance for clusters
      deposited on n-SiOx/Si that is not found on t-SiO2/Si. 

PMID- 24576990
TI  - Quantitative bounds on morphodynamics and implications for reading the
      sedimentary record.
AB  - Sedimentary rocks are the archives of environmental conditions and ancient
      planetary surface processes that led to their formation. Reconstructions of
      Earth's past surface behaviour from the physical sedimentary record remain
      controversial, however, in part because we lack a quantitative framework to
      deconvolve internal dynamics of sediment-transport systems from environmental
      signal preservation. Internal dynamics of landscapes--a consequence of the
      coupling between bed topography, sediment transport and flow dynamics
      (morphodynamics)--result in regular and quasiperiodic landforms that abound on
      the Earth and other planets. Here, using theory and a data compilation of
      morphodynamic landforms that span a wide range of terrestrial, marine and
      planetary depositional systems, we show that the advection length for settling
      sediment sets bounds on the scales over which internal landscape dynamics
      operate. These bounds provide a universal palaeohydraulic reconstruction tool on
      planetary surfaces and allow for quantitative identification of depositional
      systems that may preserve tectonic, climatic and anthropogenic signals.

PMID- 24576992
TI  - Gold nanoparticles regulate the blimp1/pax5 pathway and enhance antibody
      secretion in B-cells.
AB  - Nanoparticles are potential threats to human health and the environment; however,
      their medical applications as drug carriers targeting cancer cells bring hope to
      contemporary cancer therapy. As a model drug carrier, gold nanoparticles (GNPs)
      have been investigated extensively for in vivo toxicity. The effect of GNPs on
      the immune system, however, has rarely been examined. Antibody-secreting cells
      were treated with GNPs with diameters ranging from 2 to 50 nm. The GNPs enhanced
      IgG secretion in a size-dependent manner, with a peak of efficacy at 10 nm. The
      immune-stimulatory effect reached a maximum at 12 h after treatment but returned
      to control levels 24 h after treatment. This enhancing effect was validated ex
      vivo using B-cells isolated from mouse spleen. Evidence from RT-PCR and western
      blot experiments indicates that GNP-treatment upregulated B-lymphocyte-induced
      maturation protein 1 (blimp1) and downregulated paired box 5 (pax5).
      Immunostaining for blimp1 and pax5 in B-cells confirmed that the GNPs stimulated
      IgG secretion through the blimp1/pax5 pathway. The immunization of mice using
      peptide-conjugated GNPs indicated that the GNPs were capable of enhancing humoral
      immunity in a size-dependent manner. This effect was consistent with the bio
      distribution of the GNPs in mouse spleen. In conclusion, in vitro, ex vivo, and
      in vivo evidence supports our hypothesis that GNPs enhance humoral immunity in
      mouse. The effect on the immune system should be taken into account if
      nanoparticles are used as carriers for drug delivery. In addition to their
      toxicity, the immune-stimulatory activity of nanoparticles could play an
      important role in human health and could have an environmental impact.

PMID- 24576991
TI  - Adhesion molecules involved in neutrophil recruitment during sepsis-induced acute
      kidney injury.
AB  - Acute kidney injury (AKI) is a common complication in critically ill patients and
      is associated with high mortality. Recruitment of neutrophils is a hallmark in
      the pathogenesis of AKI. Although ischemia-reperfusion injury (IRI) is a
      frequently used research model of AKI, the clinical relevance of IRI-induced AKI
      is limited. Epidemiologically, sepsis is the prevailing cause of kidney injury.
      However, it is still unknown whether these distinct entities of AKI share the
      same pathophysiological mechanisms. This study was initiated to investigate the
      molecular mechanisms of neutrophil recruitment into the kidney in a murine model
      of sepsis-induced AKI. By using a flow cytometry-based method, we show that the
      two beta2-integrins Mac-1 and LFA-1 as well as E-selectin and P-selectin are
      involved in neutrophil recruitment into the kidney after induction of sepsis. The
      molecular mechanisms of neutrophil recruitment were further investigated using
      intravital microscopy, demonstrating that blocking one of these four molecules
      reduces the number of adherent leukocytes. This was accompanied by a renal
      upregulation of E-selectin, P-selectin and ICAM-1 (the counter-receptor of beta2
      integrins on endothelial cells) after sepsis induction. We conclude that blocking
      P-selectin, E-selectin, Mac-1 or LFA-1 protects mice from sepsis-induced AKI.

PMID- 24576993
TI  - Study of gamma irradiation effect on commercial TiO2 photocatalyst.
AB  - The aim of this work is to understand the effect of gamma irradiation on
      commercial TiO2 photocatalyst for water treatment applications. Previous studies
      concluded that gamma-irradiation is able to modify the electronic properties of
      TiO2 based photocatalysts and consequently their photocatalytic performance.
      However, there are some discrepancies in the literature where on one hand a
      significant enhancement of the material properties is reported and on the other
      hand only a weak effect is observed. In this study a surface effect on TiO2 is
      confirmed by using low and medium gamma irradiation doses. 

PMID- 24576995
TI  - Between-school variation and student characteristics associated with the accuracy
      of weight status perception among students: does the school a student attends
      impact his/her weight status perception?
AB  - Research has identified that perceived weight status is a better predictor of
      weight control behavior than actual weight status. The purpose of this study was
      to examine whether the accuracy of weight status perception varies across
      schools, and to identify the student-level characteristics associated with
      inaccurate weight status perception among 25,060 grade 9 to 12 students attending
      76 schools in Ontario, Canada. Although the majority of adolescents (60.4%) had
      accurate weight status perceptions, multi-level logistic regression analyses
      revealed significant between-school variability in the accuracy of weight status
      perceptions for both males and females. School location and school-level
      socioeconomic status were the school-level variables analyzed. We identified that
      males attending urban or suburban schools were more likely to overestimate their
      weight status compared with males attending rural schools. Important student
      level characteristics included grade, weight status, sports participation and
      social influences. Additional research is required to better understand both the
      school- and student-level characteristics associated with the accuracy of weight
      status perceptions among adolescents.

PMID- 24576994
TI  - Pannexin-1 as a potentiator of ligand-gated receptor signaling.
AB  - Pannexins are a class of plasma membrane spanning proteins that presumably form a
      hexameric, non-selective ion channel. Although similar in secondary structure to
      the connexins, pannexins notably do not form endogenous gap junctions and act as
      bona fide ion channels. The pannexins have been primarily studied as ATP-release
      channels, but the overall diversity of their functions is still being elucidated.
      There is an intriguing theme with pannexins that has begun to develop. In this
      review we analyze several recent reports that converge on the idea that pannexin
      channels (namely Panx1) can potentiate ligand-gated receptor signaling. Although
      the literature remains sparse, this emerging concept appears consistent between
      both ionotropic and metabotropic receptors of several ligand families. 

PMID- 24576996
TI  - Genomics in Coccidioides: insights into evolution, ecology, and pathogenesis.
AB  - Coccidioides immitis and C. posadasii, the causative agents of the mammalian
      disease coccidioidomycosis, are dimorphic fungal pathogens distributed throughout
      desert-like environments in North and South America. Coccidioides spp. are
      members of the Onygenales, a diverse group of pathogenic and nonpathogenic fungi.
      Recently, full genomes have been published for Coccidioides and a number of other
      Onygenales species. Phylogenomic comparisons and additional studies in
      Coccidioides population genomics and gene expression have shed light on the
      ecology and pathogenesis of Coccidioides and the other medically important
      species in this clade. Observed patterns of gene family expansion/contraction and
      evidence of gene flow have provided insight to the evolution of Coccidioides and
      greatly broadened our understanding of the diversity and sources of genetic
      variation found in fungi. In the future, expansion of the number of sequenced
      isolates from all populations will allow deeper insight into the evolutionary
      processes that have shaped this unique human pathogen. In addition, deep
      sequencing of isolates from a single Coccidioides population and pairing of those
      data with phenotype information on growth and pathogenicity for genome-wide
      association analysis will allow researchers to find genes responsible for any
      phenotype, virulence included, that shows variation in the population. 

PMID- 24576997
TI  - Characterization of Alternaria infectoria extracellular vesicles.
AB  - Many fungi use membrane vesicles to transport complex molecules across their cell
      walls. Like mammalian exosomes, fungal vesicles contain lipids, proteins, and
      polysaccharides, many of which are associated with virulence. Here we identify
      and characterize extracellular vesicles (EVs) in Alternaria infectoria, a
      ubiquitous, environmental filamentous fungus that is also an opportunistic human
      pathogen. Examination of the A. infectoria EVs revealed a morphology similar to
      that of vesicles described in other fungal species. Of note, proteomic analysis
      detected a reduced number of vesicle-associated proteins. There were two
      prevalent categories among the 20 identified proteins, including the
      polysaccharide metabolism group, probably related to plant host invasion or
      biosynthesis/degradation of cell wall components, and the nuclear proteins,
      especially DNA repair enzymes. We also found enzymes related to pigment
      synthesis, adhesion to the host cell, and trafficking of
      vesicles/organelles/molecules. This is the first time EV secretions have been
      identified in a filamentous fungus. We believe that these vesicles might have a
      role in virulence. 

PMID- 24576998
TI  - Bloodstream infections by Malassezia and Candida species in critical care
      patients.
AB  - Despite being considered an emerging yeast related to immunocompromised
      individuals, severe infections by Malassezia furfur have not been evaluated.
      During a one-year survey on yeasts fungemia, 290 neonatal and 17 pediatric
      patients with intravascular catheters, lipid parenteral nutrition, prolonged ward
      stay, and surgery were enrolled. In addition, the origin of the infection was
      investigated by swabbing hand skin of patients, parents, and healthcare workers
      and medical devices. All biological specimens and swabs were cultured on
      Sabouraud dextrose agar and Dixon agar. The yeasts identification was based on
      morphological and biochemical features and by matrix-assisted laser desorption
      ionization-time of flight mass spectrometry (MALDI-TOF MS) and confirmed by
      sequencing the internal transcribed spacer of nuclear ribosomal DNA. A higher
      prevalence of M. furfur (2.1%) over Candida spp. (1.4%) caused bloodstream
      infections (BSIs). Twelve fungemia episodes were recorded: 2 by M. furfur in a
      pediatric ward and 10 in a neonatal intensive care unit (6 caused by M. furfur
      and 4 by Candida spp.). M. furfur was also isolated from the skin of all patients
      with BSIs, from the hand skin of a parent, and from an incubator surface and
      sheet. Patients with Candida spp. and M. furfur BSIs were successfully treated
      with intravenous liposomal Amphotericin B. These findings highlight the need for
      a more accurate etiological diagnosis in high-risk patients by adding lipid
      supplemented culture media for Malassezia in the current mycological routine as
      the clinical features, patient management, and outcomes in both Candida and
      Malassezia fungemia do not differ. 

PMID- 24577000
TI  - Dual localization of Mdj1 in pathogenic fungi varies with growth temperature.
AB  - Paracoccidioides brasiliensis and P. lutzii are temperature-dependent dimorphic
      fungi that cause paracoccidioidomycosis (PCM). Previously, we characterized the
      PbMDJ1 gene. This gene encodes P. brasiliensis chaperone Mdj1, which in yeast is
      a mitochondrial member of the J-domain family, whose main function is to regulate
      cognate Hsp70 activities. We produced rabbit polyclonal antibody antirecombinant
      PbMdj1 (rPbMdj1), which labeled the protein not only in mitochondria but also at
      the cell wall of P. brasiliensis yeasts of isolate Pb18. Here we used anti
      rPbMdj1 in confocal microscopy to localize Mdj1 in Pb18 and other fungal isolates
      grown at different temperatures. Dual intracellular and cell surface pattern were
      initially seen in yeast-phase P. brasiliensis Pb3, Pb18 (control), P. lutzii
      Pb01, and Histoplasma capsulatum. Pb18 and Aspergillus fumigatus hyphae as well
      as Pb3 pseudo hyphae formed at 36 degrees C were labeled predominantly along the
      cell surface. Preferential surface localization was observed by 72 h of yeast
      mycelium thermotransition. It was interesting to observe that anti-rPbMdj1
      concentrated at the surface tip and branching points of A. fumigatus hyphae grown
      at 36 degrees C, suggesting a role in growth, whereas at 23 degrees C, anti
      rPbMdj1 was distributed along the hyphal surface. In Pb3, Pb18, and Pb01
      mitochondrial extracts, the antibodies revealed a specific 55-kDa band, which
      corresponds to the processed Mdj1 size. The presence of Mdj1 on the fungal cell
      wall suggests that this protein could also play a role in the interaction with
      the host. 

PMID- 24576999
TI  - Paradoxical antifungal activity and structural observations in biofilms formed by
      echinocandin-resistant Candida albicans clinical isolates.
AB  - Echinocandin-resistant clinical isolates of Candida albicans have been reported,
      and key-hot spot mutations in the FKS1 gene, which encodes a major glucan
      synthase subunit, have been identified in these (caspofungin-resistant [CAS-R])
      strains. Although these mutations result in phenotypic resistance to
      echinocandins in planktonic cells, there is little data on antifungal
      susceptibilities of CAS-R C. albicans strains within biofilms. Thus, we analyzed
      biofilms formed by 12 C. albicans CAS-R clinical strains in which we previously
      identified FKS1 hot-spot mutations and compared the sessile antifungal and
      paradoxical activity of anidulafungin (ANID), caspofungin (CAS), and micafungin
      (MICA). Biofilms were formed in a 96-well static microplate model and assayed
      using both tetrazolium-salt reduction and crystal violet assays, as well as
      examination by scanning electron microscopy. We first sought to assess biofilm
      formation and structure in these fks1 mutants and found that the biofilm mass and
      metabolic activities were reduced in most of the fks1 mutants as compared with
      reference strain SC5314. Structural analyses revealed that the fks1 mutant
      biofilms were generally less dense and had a clear predominance of yeast and
      pseudohyphae, with unusual "pit"-like cell surface structures. We also noted that
      sessile minimum inhibitory concentrations (MICs) to ANID, CAS, and MICA were
      higher than planktonic MICs of all but one strain. The majority of strains
      demonstrated a paradoxical effect (PE) to particular echinocandins, in either
      planktonic or sessile forms. Overall, biofilms formed by echinocandin-resistant
      clinical isolates demonstrated varied PEs to echinocandins and were structurally
      characterized by a preponderance of yeast, pseudohyphae, and pit-like structures.

PMID- 24577001
TI  - Genetic analysis of the endemic fungal pathogens Coccidioides posadasii and
      Coccidioides immitis in Mexico.
AB  - Coccidioidomycosis (CM) is a mycotic disease that affects mammals, including
      humans. Official data relative to CM in Mexico has not been collected since 1995,
      thus its prevalence remains unknown. The objectives of this study were to
      identify the predominant Coccidioides species in Mexico, infer their current
      geographical distribution and explore the correlation between species and
      clinical presentation. We collected 154 strains, which were cultured,
      inactivated, and processed for DNA extraction. Nine microsatellite loci, the
      Ag2/PRA gene and Umeyama Region were amplified from each isolate. To infer the
      current geographical distribution of Coccidioides spp. and to establish a
      correlation between genotype and clinical presentation, we evaluated genetic
      population structure under the following grouping criteria: putative origin and
      clinical presentation records. Microsatellite analysis showed that 82% of the
      isolates corresponded to C. posadasii and 18% were C. immitis. The species
      identification results obtained using Umeyama region, Ag2/PRA, and
      microsatellites of five of the isolates were inconsistent with the data collected
      for the remaining isolates. C. posadasii strains were found primarily in the
      northeastern region and C. immitis in the northwestern region. However, there was
      no relationship between clinical presentation and Coccidioides species. The
      molecular markers used in this study proved to have a high power of resolution to
      identify the Coccidioides species recovered in culture. While we found C.
      posadasii to be the most abundant species in Mexico, more detailed clinical
      records are needed in order to obtain more accurate information about the
      infections in specific geographical locations. 

PMID- 24577002
TI  - RNAi-mediated silencing of fungal acuD gene attenuates the virulence of
      Penicillium marneffei.
AB  - A number of pathogens, most of them intracellular, employ the glyoxylate cycle in
      order to ingest fatty acids as carbon sources as a way of coping with nutrient
      deprivation during the infection process. Isocitrate lyase, which is encoded by
      the pathogen's acuD gene, plays a pivotal role in the glyoxylate cycle, which has
      been implicated in fungal pathogenesis. In this study, the acuD gene of
      Penicillium marneffei was knocked down using siRNA expressed by a filamentous
      fungi expression system. The acuD siRNA reduced the acuD gene's mRNA and protein
      expression by 21.5 fold and 3.5 fold, respectively. When macrophages were
      infected with different transformants of P. marneffei, the knockdown of acuD
      expression with RNA interference was lethal to the pathogens. In addition, the
      secretion of tumor necrosis factor-alpha and interferon-gamma from the infected
      macrophages was reduced. Moreover, the RNAi-mediated silencing of acuD expression
      reduced the fungal burden in the nude mice infected with P. marneffei; inhibited
      the inflammatory response in the lungs, livers, and spleens during the chronic
      phase instead of the acute phase of infection; and thus prolonged survival of the
      infected animals. Collectively, our data indicate that the RNAi-mediated
      silencing of acuD expression could attenuate virulence of P. marneffei. The
      endogenous expression of the delivered siRNA vector could be used to evaluate the
      role of functional genes by continuous and stable expression of siRNA. 

PMID- 24577003
TI  - An opportunistic human pathogen on the fly: strains of Aspergillus flavus vary in
      virulence in Drosophila melanogaster.
AB  - Aspergilloses are fungal diseases in humans and animals that is caused by members
      of the genus Aspergillus. Aspergillus flavus is an important opportunistic
      pathogen, second only to A. fumigatus as a cause of human aspergillosis.
      Differences in virulence among A. flavus isolates from clinical and other
      substrates and mating types are not well known. The fruit fly Drosophila
      melanogaster has become a model organism for investigating virulence of human
      pathogens due to similarities between its immune system and that of mammals. In
      this study we used D. melanogaster as a model host to compare virulence among A.
      flavus strains obtained from clinical sources as compared with other substrates,
      between isolates of different mating types, and between isolates of A. flavus and
      A. fumigatus. Anesthetized flies were infected with A. flavus; mortality ranged
      from 15% to >90%. All strains were virulent, but some were significantly more so
      than others, which in turn led to the wide mortality range. Clinical strains were
      significantly less virulent than environmental strains, probably because the
      clinical strains were from culture collections and the environmental strains were
      recent isolates. Mean virulence did not differ between MAT1-1 and MAT1-2 mating
      types and the phylogeny of A. flavus isolates did not predict virulence. A.
      flavus was on average significantly more virulent than A. fumigatus on two lines
      of wild-type flies, Canton-S and Oregon-R. D. melanogaster is an attractive model
      to test pathogenicity and could be useful for identifying genes involved in
      virulence. 

PMID- 24577004
TI  - Identification and typing of the Candida parapsilosis complex: MALDI-TOF MS vs.
      AFLP.
AB  - In this study we compare the capability of amplification fragment-length
      polymorphism (AFLP) and matrix-assisted laser desorption/ionization time-of
      flight mass spectrometry (MALDI-TOF MS) to identify and subtype isolates of
      members of the Candida parapsilosis complex (C. parapsilosis, C. orthopsilosis,
      C. metapsilosis) and Lodderomyces elongisporus, which cannot be differentiated
      with biochemical methods. Both techniques correctly identified all isolates
      included in this study and clustered isolates within the different species. DNA
      based and mass spectrum-based dendrograms yielded similar outcomes with regard to
      phylogenetic distance within C. orthopsilosis and C. parapsilosis species.
      However, a different clustering was obtained for C. metapsilosis for which AFLP
      was highly effective in differentiating. While MALDI-TOF MS was found to be a
      reliable method for species-level identification, further studies are required to
      assess its value as a fungal typing tool.

PMID- 24577005
TI  - Trichophyton onychocola sp. nov. isolated from human nail.
AB  - A previously undescribed Trichophyton species was isolated from the nail of a 33
      year-old man with a history of probable distal lateral subungual onychomycosis
      (without confirmation by mycological examination). The infection occurred for the
      first time five years earlier (in 2006) and affected the right great toenail,
      with complete clinical remission after treatment with ciclopirox olamine. This
      undescribed species was isolated during probable relapse in 2011, but its
      etiological significance was not confirmed, that is, direct microscopy was
      negative and additional clinical samples were not collected. The species is
      probably geophilic based on phylogenetic analysis (internal transcribed spacer
      [ITS] rDNA) and is most closely related to the anamorphic T. thuringiense,
      homothallic Arthroderma ciferrii (anamorph T. georgiae), and heterothallic A.
      melis. The new species is characterized by yellowish colonies, red reverse on
      several media, positive urease test, negative hair-perforation test, absence of
      growth at 34 degrees C, absence of macroconidia, formation of one-celled clavate
      microconidia, and spiral hyphae. The species grows well on sterilized human hairs
      placed on agar medium without any additional nutrients and forms gymnothecium
      like structures covered by peridial hyphae. The combination of unique micro- and
      macromorphological features and physiological and sequence data from four
      unlinked loci (ITS, benA, RPB2, and act1 gene) justified the proposal of a new
      species T. onychocola sp. nov. 

PMID- 24577006
TI  - IFN-gamma impairs Trichophyton rubrum proliferation in a murine model of
      dermatophytosis through the production of IL-1beta and reactive oxygen species.
AB  - Trichophyton rubrum is the main etiological agent of dermatophytosis, an
      infection of the skin that affects millions of people worldwide. In this study,
      we developed a murine model of the dermatophytosis caused by T. rubrum in which
      C57BL/6 wild-type, interleukin (IL)-12(-/-), and interferon-gamma (IFN-gamma(-/
      )) mice were inoculated with 1 * 10(6) conidia/animal. The fungal burden,
      myeloperoxidase and N-acetylglucosaminidase activities, cytokine and chemokine
      profiles, and histopathology of the skin were evaluated on the seventh and
      fourteenth days post infection. Phagocytic indices, intracellular proliferation
      rates, and oxidative bursts generated by macrophages from WT and IFN-gamma(-/-)
      mice were determined. On day 7 post infection, higher fungal burdens were
      observed comparison with burdens on day 14 post infection. The IL-12(-/-) and IFN
      gamma(-/-) mice showed higher fungal burdens on the skin and lower levels of IL
      1beta. Conversely, the WT mice showed lower fungal burdens with higher production
      of TNF-alpha, IL-1beta, and chemokine ligand 1/keratinocyte chemoattractant
      (CXCL1/KC). The macrophages from WT mice proved to be more efficient at engulfing
      and killing T. rubrum conidia through the production of reactive oxygen species.
      The results show that our model is a useful tool for understanding the
      pathogenesis of dermatophytosis caused by T. rubrum and that IL-12 and IFN-gamma
      are pivotal in controlling the infection through the recruitment and activation
      of neutrophils and macrophages. 

PMID- 24577007
TI  - Itraconazole vs. trimethoprim-sulfamethoxazole: A comparative cohort study of 200
      patients with paracoccidioidomycosis.
AB  - Paracoccidioidomycosis (PCM) is a systemic mycosis endemic to Latin America.
      Brazil accounts for approximately 80% of cases, where it represents a major
      public health issue due to its disabling impact and the number of premature
      deaths it causes. We present a retrospective cohort study that was conducted in
      order to better understand factors that relate to cure of the infection in the
      treatment of 200 patients with PCM. We evaluated the influence of
      sociodemographic and clinical factors as well as therapeutic regimen
      (trimethoprim-sulfamethoxazole [TMP-SMX] and itraconazole) on the progress of PCM
      (cure and noncure). There was a higher incidence of cure (83%) among patients who
      regularly received treatment for their infections and completed the treatment
      protocol. Moreover, itraconazole (86.4%) was significantly superior to TMP-SMX
      (51.3%) in terms of cure rate and had a median treatment period that was
      significantly shorter (12 months) than that for TMP-SMX (23 months). A Cox
      proportional hazard regression model showed that use of itraconazole increased
      the hazard of cure, regardless of sex, age, education, clinical form, completion
      of treatment, and regularity. Although the results of this study show that
      itraconazole was the best treatment option for PCM patients, a double-blind,
      randomized, controlled trial is necessary to confirm this conclusion. 

PMID- 24577008
TI  - Virulence of South African Candida albicans strains isolated from different
      clinical samples.
AB  - Candida albicans is a dimorphic opportunistic pathogenic yeast that is commonly
      isolated from different anatomical sites and clinical samples. It possesses
      several virulence factors, including secretion of hydrolytic enzymes, the ability
      to adhere to abiotic surfaces and cells, and the ability to penetrate tissues. We
      determined the level of in vitro expression of virulence factors by South African
      clinical C. albicans strains and the correlation among them. Furthermore, we
      determined whether there is a correlation between the levels of virulence factors
      expressed by a strain and the anatomical site from which it was isolated. The
      overall virulence of strains expressing different levels of these virulence
      factors in vitro was examined using a chorioallantoic membrane (CAM) chicken
      embryo model of infection, with variations observed in the production of
      hydrolytic enzymes. Most strains were able to produce in vitro high levels of
      protease and phospholipase and medium levels of lipase. Using the quantitative
      agar invasion assay, most strains were found to be highly invasive. No
      relationships of virulence factors produced in vitro were observed, except for a
      weak negative correlation between protease activity and invasiveness, as well as
      protease activity and cell surface hydrophobicity. There was no indication that
      the in vitro differences in virulence factors were correlated with virulence in
      the CAM model. However, we found that the infection model is sensitive enough to
      distinguish different virulence levels of strains. 

PMID- 24577009
TI  - Mycetyoma in a horse--curtains.

PMID- 24577010
TI  - Usefulness of pan-fungal NASBA test for surveillance of environmental fungal
      contamination in a protected hematology unit.
AB  - A pan-fungal nucleic acid sequence based applification (NASBA) test was adapted
      and used for the first time to detect and quantify the level of filamentous fungi
      in environmental samples. Surface samples (n = 356) collected in a controlled air
      flow hematology ward were tested by mycological culture and the pan-fungal NASBA
      test. The overall percentage of agreement between culture and NASBA was 88%, the
      Kappa coefficient was equal to 0.61 (95%CI = [0.51; 0.72]). This pan-fungal NASBA
      test could be a promising tool to rapidly monitor the absence of molds in
      controlled environments. 

PMID- 24577011
TI  - Evaluation of in vivo pathogenicity of Candida parapsilosis, Candida
      orthopsilosis, and Candida metapsilosis with different enzymatic profiles in a
      murine model of disseminated candidiasis.
AB  - Six isolates of the Candida parapsilosis complex with different enzymatic
      profiles were used to induce systemic infection in immunocompetent BALB/c mice.
      Fungal tissue burden was determined on days 2, 5, 10, and 15 post challenge. The
      highest fungal load irrespective of post-infection day was detected in the
      kidney, followed by the spleen, lung, and liver, with a tendency for the fungal
      burden to decrease by day 15 in all groups. Significant differences among the
      strains were not detected, suggesting that the three species of the "psilosis"
      group possess a similar pathogenic potential in disseminated candidiasis
      regardless of their enzymatic profiles. 

PMID- 24577012
TI  - An invertebrate model to evaluate virulence in Aspergillus fumigatus: the role of
      azole resistance.
AB  - The impact of different mutations in the Aspergillus fumigatus ergosterol
      biosynthesis pathway on pathogenesis has been evaluated using a simple
      invertebrate mini host, the caterpillar Galleria mellonella. A set of strains
      that includes clinical isolates and isogenic mutants with mutations at the cyp51A
      gene conferring azole resistance were studied. All strains demonstrated a similar
      in vitro growth pattern and are equally virulent against the insect larvae. These
      results suggest that in A. fumigatus acquisition of this particular azole
      resistance mechanism would not imply any significant change in virulence. G.
      mellonella may provide a convenient and inexpensive model for the in vivo
      prescreening of mutants of A. fumigatus, contributing to the generation of a
      hypotheses that can be further tested in refined experiments in mammalian models.

PMID- 24577014
TI  - Locating the center of resistance in individual teeth via two- and three
      dimensional radiographic data.
AB  - OBJECTIVES: The preferred reference point to describe the force-moment system
      exerted upon a tooth is its center of resistance (CR). Morphological data on the
      dentoalveolar complex can be used to locate this point either three-dimensionally
      (3D) with the finite element (FE) method, or two-dimensionally (2D) with a
      mathematical method calculating the centroid of the projected dental root. This
      study aimed to compare and appraise these two methods with regard to their
      accuracy and time requirements. METHODS: Three radiological datasets with
      permanent teeth were included. Each single 3D dataset was used in each of these
      patients to derive both a 3D and 2D morphological model of the upper right
      central incisor. CR levels were evaluated in percent, indicating the relative
      height as measured from the (averaged levels of the mesial and distal) bony ridge
      margin to the tooth's apex. RESULTS: Mean CR levels of 42.8% for distalization
      and 56.5% for lingual movement were obtained from the 3D FE simulations of
      initial tooth movement. The 2D mathematical model yielded a mean CR level of
      44.5%. Compared to this mathematical approach, the 3D FE simulations were around
      15 times more time-consuming, with an interactive requirement of around 15 h.
      CONCLUSION: Because they contain so much more morphological information, 3D FE
      simulations should offer superior predictability. In addition, they are the only
      method offering detailed CR identification for specific directions of tooth
      movement. Before this method can be used in clinical practice, however, there is
      still a major need to reduce time requirements via further automation of process
      steps and to investigate how it should be applied to different tooth types.

PMID- 24577015
TI  - Treatment efficiency of mini-implant-borne distalization depending on age and
      second-molar eruption.
AB  - OBJECTIVE: The aim of this study was to evaluate the efficiency of molar
      distalization depending on age and second-molar eruption using the Beneslider.
      MATERIALS AND METHODS: Treatment of 51 patients (mean age 17.8 +/- 9.6 years) was
      investigated retrospectively by means of pre- and posttreatment cephalograms.
      Patients were divided into three groups: 14 children with unerupted upper second
      molars (group 1), 23 adolescents with second molar in place (group 2), and 14
      adults (group 3). The distalization forces applied were 2.4 N in group 1 and 5.0
      N in groups 2 and 3. Treatment changes were evaluated and examined statistically
      for significant differences. RESULTS: In all patients a Class I molar
      relationship was achieved. All mini-implants remained stable during treatment.
      Mean distalization distance as measured by the displacement of the center of
      resistance was 3.6 +/- 1.9 mm (range 1.2-8.5 mm depending on treatment needs).
      Since no significant tipping was detected, the type of movement can be described
      as bodily movement. Mean overall distalization speed was 0.6 +/- 0.4 mm per
      month. There were no statistical differences between the groups. CONCLUSION: We
      found the Beneslider to be an effective appliance that enables bodily
      distalization in adequate treatment time. The higher resistance due to erupted
      second molars can be compensated by the use of higher forces without
      significantly reducing distalization speed.

PMID- 24577018
TI  - Dental findings and identification of undiagnosed hyperglycemia.

PMID- 24577017
TI  - Metric precision via soft-tissue landmarks in three-dimensional structured-light
      scans of human faces.
AB  - OBJECTIVES: The goal of the current work was to investigate the suitability of
      ten facial soft-tissue landmarks (trichion, glabella, nasion, left and right
      orbital, subnasal, left and right porion, pogonion, gnathion) as reference points
      for metric facial analysis by analyzing their intra- and interserial precision in
      all three dimensions. METHODS: The faces of 32 volunteers were scanned using a
      standardized protocol with a structured-light scanner (FaceSCAN(3D) Scientific
      Photolab 60 Hz; 3D Shape, Erlangen, Germany). Three examiners placed the
      landmarks twice within a 2-week interval. Image processing (Onyx Ceph(3); Image
      Instruments; Chemnitz, Germany) and statistical (SAS 9.2; SAS Institute, Cary,
      NC, USA) software was used for analysis. All measurements were corrected for mean
      values per patient and analyzed for intraserial and interserial error by model II
      ANOVA for a simple classification with random effects. RESULTS: Median
      intraserial precision was 0.40 mm (range 0.05-1.01 mm) overall, including 0.40 mm
      (0.33-0.85 mm) on the x-axis, 0.64 mm (0.36-0.87 mm) on the y-axis, and 0.27 mm
      (0.05-1.01 mm) on the z-axis. Interserial precision was substantially lower at a
      median of 0.05 mm (0-0.22 mm), often not statistically assessable with
      intraserial precision. We observed no landmark-associated differences; in
      particular, the medians of the bilateral landmarks orbital (intraserial: 0.40 mm;
      interserial: 0.02 mm) and porion (intraserial: 0.36 mm; interserial: small and
      not assessable) were in the middle of the range of our results. Trichion
      (intraserial: 0.73 mm; interserial: 0.05 mm) and gnathion (intraserial: 0.87 mm;
      interserial: 0.20 mm) revealed the highest degrees of intraserial measurement
      imprecision. Outliers were identified in 1.2% (64 of 5400) of measurements.
      CONCLUSION: All selected landmarks offer suitably high levels of intra- and
      interserial precision for the three-dimensional (3D) metric assessment of facial
      soft-tissue parameters. No difference between (bi)lateral and facial midline
      landmarks was noted.

PMID- 24577020
TI  - Surface-enhanced Raman scattering on aluminum using near infrared and visible
      excitation.
AB  - We observed strong surface-enhanced Raman scattering on discontinuous
      nanostructured aluminum films using 785 nm excitation even though dielectric
      constants of this metal suggest plasmon supported spectroscopy in the ultraviolet
      range. The excitation of SERS correlates with plasmon resonances in the 1.3-2.5
      eV range identified in electron energy loss spectra. 

PMID- 24577016
TI  - Three-dimensional investigation of facial surface asymmetries in skeletal
      malocclusion patients before and after orthodontic treatment combined with
      orthognathic surgery.
AB  - OBJECTIVES: The goal of the following study was to quantify facial soft-tissue
      asymmetry in patients with pronounced skeletal malocclusion anomalies before and
      after orthodontic treatment combined with orthognathic surgery. In addition, the
      facial attractiveness of these patients was rated by dental specialists and
      laypersons both before and after treatment based on the three-dimensional (3D)
      data. PATIENTS AND METHODS: An optical sensor was used to noninvasively capture
      the 3D facial surface data of 60 adult patients including two groups of 20
      patients with skeletal Class II or III anomalies and a control group of another
      20 subjects with Class I relationships. Facial surface asymmetries were evaluated
      immediately before the surgical procedure and 1 year thereafter. In addition,
      subjective ratings of facial attractiveness were obtained based on a
      questionnaire from orthodontists, maxillofacial surgeons, and laypersons.
      RESULTS: No differences in facial soft-tissue asymmetry were observed between the
      Class II and III patients either pre- or postoperatively, but asymmetry was found
      to be more pronounced in the skeletal malocclusion groups than in the Class I
      control group both pre- and postoperatively. The subjective ratings of facial
      attractiveness by the various rater groups yielded more favorable results for the
      post- than preoperative patient images, reflecting differences that reached
      overall statistical significance. CONCLUSION: Quantitative analysis of facial
      soft-tissue asymmetry and calculating a cutoff value allowed us to distinguish
      patients with skeletal malocclusion from a control group solely on the basis of
      asymmetry. Combined regimens of orthodontic treatment and orthognathic surgery go
      some way in reducing asymmetry toward the levels seen in untreated control
      subjects, while the asymmetry pattern characteristic of this type of malocclusion
      will persist. Nevertheless, the asymmetry reduction is noticeable enough to
      result in more favorable ratings of attractiveness.

PMID- 24577019
TI  - Efficacy and safety of early dexmedetomidine during noninvasive ventilation for
      patients with acute respiratory failure: a randomized, double-blind, placebo
      controlled pilot study.
AB  - BACKGROUND: Successful application of noninvasive ventilation (NIV) for acute
      respiratory failure (ARF) requires patient cooperation and comfort. The efficacy
      and safety of early IV dexmedetomidine when added to protocolized, as-needed IV
      midazolam and fentanyl remain unclear. METHODS: Adults with ARF and within 8 h of
      starting NIV were randomized to receive IV dexmedetomidine (0.2 MUg/kg/h titrated
      every 30 min to 0.7 MUg/kg/h to maintain a Sedation-Agitation Scale [SAS] score
      of 3 to 4) or placebo in a double-blind fashion up to 72 h, until NIV was stopped
      for >= 2 h, or until intubation. Patients with agitation (SAS >= 5) or pain
      (visual analog scale >= 5 of 10 cm) 15 min after each dexmedetomidine and placebo
      increase could receive IV midazolam 0.5 to 1.0 mg or IV fentanyl 25 to 50 MUg,
      respectively, at a minimum interval of every 3 h. RESULTS: The dexmedetomidine (n
      = 16) and placebo (n = 17) groups were similar at baseline. Use of early
      dexmedetomidine did not improve NIV tolerance (score, 1 of 4; OR, 1.44; 95% CI,
      0.44-4.70; P = .54) nor, vs. placebo, led to a greater median (interquartile
      range) percent time either tolerating NIV (99% [61%-100%] vs. 67% [40%-100%], P =
      .56) or remaining at the desired sedation level (SAS score = 3 or 4, 100% [86%
      100%] vs. 100% [100%-100%], P = .28], or fewer intubations (P = .79). Although
      use of dexmedetomidine was associated with a greater duration of NIV vs placebo
      (37 [16-72] vs. 12 [4-22] h, P = .03), the total ventilation duration (NIV +
      invasive) was similar (3.3 [2-4] days vs. 3.8 [2-5] days, P = .52). More patients
      receiving dexmedetomidine had one or more episodes of deep sedation vs placebo
      (SAS <= 2, 25% vs. 0%, P = .04). Use of midazolam (P = .40) and episodes of
      either severe bradycardia (heart rate <= 50 beats/min, P = .18) or hypotension
      (systolic BP <= 90 mm Hg, P = .64) were similar. CONCLUSIONS: Initiating
      dexmedetomidine soon after NIV initiation in patients with ARF neither improves
      NIV tolerance nor helps to maintain sedation at a desired goal. Randomized,
      multicenter trials targeting patients with initial intolerance are needed to
      further elucidate the role for dexmedetomidine in this population.

PMID- 24577021
TI  - [Odontogenic maxillary sinusitis: peculiarities of diagnostics and treatment].
AB  - The objective of the present work was to improve the quality of diagnostics and
      the choice of optimal therapy for the management of odontogenic maxillary
      sinusitis associated with the localization of foreign bodies in the lateral parts
      of the maxillary sinuses. To this effect, multispiral computed tomography was
      used to enable the exact location of the foreign body inside the sinus and to
      choose the optimal approach for the surgical intervention. The modified Coldwell
      Luc procedure was employed as the most adequate technique in the given clinical
      condition. 

PMID- 24577022
TI  - [Peculiarities of the application of a multi-angle endoscopy during surgical
      interventions on the ethmoidal and sphenoidal sinuses: the anatomical study].
AB  - This work was designed to carry out the postmortem evaluation of the potential of
      using a multi-angle endoscope for endonasal surgical interventions on the
      ethmoidal and sphenoidal sinuses. The study was performed on 5 fresh cadavers (10
      sides). It was shown that the range of the angles and directions of view during
      dissection of ethmoidal sinuses is 10-50 degrees and 360 degrees respectively.
      The use of an Acclarent Cyclops endoscope made it possible to visualize all walls
      of the sphenoidal sinus through the enlarged aperture which confirms the higher
      effectiveness of this instrument compared with the traditional endoscopes having
      the fixed angle of view of 0, 30, 45, and 70 degrees. The disadvantages of the
      Acclarent Cyclops endoscope are its heavier weight and a somewhat poorer quality
      of the screen image of the operative field. 

PMID- 24577023
TI  - [Changes in the mucous membrane of the patients with chronic maxillary sinusitis
      caused by foreign bodies].
AB  - The objective of the present work was to study the morphofunctional changes in
      maxillary sinus mucosa of the patients with odontogenic maxillary sinusitis (OMS)
      associated with the presence of a foreign body depending on its duration. A total
      of 105 hospitalized patients were examined and operated. Biopsy samples taken
      from mucosa and contents of the maxillary sinuses during surgery were
      investigated. The histological study included the standard sample processing
      followed by paraffin embedding of the material and staining of the
      micropreparations with hematoxylin and eosin. It was shown that foreign bodies
      present in the maxillary sinuses cause marked structural reorganization of the
      mucous membrane usually with the predominance of hypertrophic and polypous
      changes.

PMID- 24577024
TI  - [Surgical radioprotection of the postoperative cavities for the optimization of
      radiotherapy of common cancer of paranasal sinuses and prophylaxis of local
      radiation-induced lesions].
AB  - The analysis of the literature publications and original clinical observations
      (27 cases) provided a basis for the consideration and generalization of the
      results of the combined radical surgical treatment of common cancer of paranasal
      sinuses with the elements of craniobasal and craniofascial plastic reconstruction
      of the postoperative cavities with a view to optimization of radiotherapy and
      radioprotection of the intact tissues. The role of the proposed methods in the
      combined treatment of cancer of paranasal sinuses is evaluated. Special emphasis
      is laid on the importance of radioprotection for the prevention of radiation
      induced epitheliitis in the reconstructed cavities following resection of the
      upper jaw, sino-orbital exenteration, and hemifacial resection. 

PMID- 24577025
TI  - [Peculiar features of the coagulation, fibrinolytic, and anticoagulation systems
      of blood in the patients presenting with vascular ENT tumours].
AB  - The objective of the present work was to study characteristics of the blood
      coagulation system in the patients presenting with vascular ENT tumours including
      the following parameters: a complete blood count, hemorrhage, coagulation,
      retraction, and blood clot lysis times. The patients with ENT hemangiomas
      experienced hypocoagulation in the preoperative period in combination with the
      predominance of the fibrinolytic processes and elevated levels of free heparin.
      These changes can be interpreted as a protective reaction to prevent
      intravascular coagulation in the case of the slow blood flow in hemangiomatous
      cavities. The results of the study indicate that the prophylactic administration
      of inhibitors of enhanced fibrinolysis in the preoperative period may be
      dangerous for the patients presenting with hemangiomas because suppression of
      this adaptive response prior to surgery is likely to promote massive
      microcoagulation under the influence of tissue thromboplastin. 

PMID- 24577026
TI  - [Analysis of the causes of cancer negligence and low survival in the patients
      with malignant neoplasms of ENT and oral cavity in the city of Moscow].
AB  - The objective of the present study was to elucidate the causes of late detection
      of malignant neoplasms of ENT and oral cavity and low survival of the patents
      with these tumours in Moscow. The secondary objective was to elaborate the
      organizational measures for reducing the level of negligence and mortality from
      these malignancies among the city population. It was shown that the main cause
      behind the negligence is the late application of the patients for the medical
      assistance. Next in importance are asymptomatic clinical course of the disease in
      the absence of the pathognomonic and early signs of malignant neoplasms, a
      combination of several pathologies, imperfection of medical knowledge, and the
      poor resolving power of the modern methods. It is emphasized that the lack of
      vigilance against cancer among the practicing health providers is one of the main
      causes of medical errors. A few ways to address the problem of negligence with
      respect to malignant neoplasms of ENT and oral cavity in Moscow are proposed. 

PMID- 24577027
TI  - [Hearing disorders in young subjects].
AB  - The objective of the present work was to study the state of the hearing function
      and the prevalence of ear pathologies in the applicants and students of a higher
      education institution. A total of 44.525 subjects at the age varying from 15 to
      30 years were available for the examination of whom 42.829 ones were involved in
      the routine medical examination programs for the applicants and students; 1696
      persons presenting with acute ear diseases and impairment of hearing passed the
      primary medical examination in the University polyclinic. The hearing function
      was evaluated with the help of the speech and tuning fork tests; in part of the
      patients it was evaluated by tonal threshold audiometry in both the standard and
      the extended frequency ranges, tympanometry, registration of the ipsilateral
      acoustic reflex, and a questionnaire study. Chronic ear pathology is known to
      occur in 1.77-2.09% of the young people; it is the third most frequent condition
      after diseases of throat, nose, and paranasal sinuses in the structure of chronic
      ENT morbidity. The structure of chronic ear diseases is dominated by Eustachian
      tube pathology (0.99-1.4%) followed by chronic middle and inner ear diseases
      (0.35-0.62% and 0.15-0.26% respectively). The commonest chronic disease of the
      middle ear is adhesive otitis media that is accompanied by the conductive
      impairment of hearing in 53.5% of the cases. Next in importance is chronic
      suppurative otitis media associated with the conductive or mixed-type loss of
      hearing in 91.7% of the patients. The subclinical form of sensorineural hearing
      loss was found in 11.7-15.1% of the young subjects Including minimal
      sensorineural hearing loss (enhancement of the hearing threshold by 1-3
      frequencies) in 11.7-12.4% of the patients. A frequent cause of impaired hearing
      in the case of chronic sensorineural hearing loss is a single or repeated
      acoustic trauma. 

PMID- 24577028
TI  - [Tympanometry in the premature infants of different gestational age during the
      primary audiological examination].
AB  - The objective of the present work was to study specific approaches of
      tympanometry in the premature infants of different gestational age. A total of
      122 typmanograms (243 ears) were available for the analysis. Peculiarities of
      recording tympanograms and their characteristics in the premature infants of
      different gestational age (including static compliance, intratympanic pressure,
      and tympanogram width) have been demonstrated. The optimal frequency of
      tympanometry in the premature infants of different gestational age was
      determined. 

PMID- 24577029
TI  - [Unknown pathogens from the human oral microflora of interest for
      otorhinolaryngology].
AB  - The identification of microorganisms from the human oral cavity is a topical
      problem in many clinical disciplines including otorhinolaryngology. Many
      bacterial species of oral microbiota are causative agents of ENT diseases, and
      poor conditions of the oral cavity, unhealthy teeth and gums increase the risk of
      the spread of infection. The objective of the present study was to distinguish
      and identify poorly explored and previously unknown aerobic opportunistic
      pathogenic microorganisms responsible for various ENT disorders. The normal
      microflora remains to be thoroughly studied with the use of the new culturing
      techniques that ensure the isolation of pure microbial cultures. The present
      publication reports for the first time isolation of the stable mixed microbial
      biofilms formed by unrelated bacterial species and containing the yet unknown
      microorganisms. The isolated bacteria were identified as previously unknown or
      poorly unexplored anaerobic opportunistic species capable of inducing ENT
      pathology; their sensitivity to antibiotics was evaluated.

PMID- 24577030
TI  - [Diagnostics of olfactory disorders in the patients with Parkinson's disease and
      polypous sinusitis with the use of the Sniffin' Sticks test].
AB  - The objective of the present study was the characteristic of the sense of smell
      and comparison of its peculiarities in the patients presenting with Parkinson's
      disease and polypous sinusitis based on the results of otorhinolaryngological
      examination with the use of the Sniffin' Sticks test. A total of 31 patients with
      polypous rhinosinusitis (PRS) (18 men and 17 women at the age of 44-58 years )
      and 97 patients with Parkinson's disease (PD) (47 men and 50 women at the age of
      50-56 years) were enrolled in the study. It was shown that 85% of the patients
      with PRS and PD suffered from olfactory disorders. The evaluation of selected
      parameters determined by the Sniffin' Sticks test demonstrated the impairment of
      the sense of smell in 48% of the patients with PRS and in 54% of those having PD.
      The main difference between the two groups was in the odour threshold that was
      reduced in 97% of the patients with PRS and in 72% of the cases with PD and in
      the ability to distinguish between odours that was compromised in 37% and 78% of
      these patients respectively. 

PMID- 24577031
TI  - [Comparison of the results of acoustic analysis of the voice recorded by
      different methods].
AB  - This study was carried out with the purpose of estimating the possibility of the
      acoustic analysis of the voice recorded with the use of a handsfree telephone.
      The voices of 40 subjects were analysed with the help of the special software
      program. The recordings obtained with the help of the handsfree telephone and
      over a usual microphone were compared. The following parameters were determined:
      the frequency of the fundamental speech tone when reading a text and jitter,
      shimmer and the signal to noise (S/N) ratio when phonating the letter "a".
      Statistical analysis of the data obtained failed to reveal the significant
      difference between the values of the parameters of interest, such as the main the
      frequency, jitter, shimmer, and the S/N ratio, in both modes of recording
      (p>0.05).The results of the study confirm the possibility of acoustic analysis of
      the voice over the telephone.

PMID- 24577032
TI  - [The effectiveness of propranolol therapy of subfold hemangioma in the children
      during the first year of life].
AB  - The objective of the present study was to estimate the effectiveness and
      tolerance of propranolol therapy prescribed to the children presenting with
      vascular hyperplasia of the larynx. The experience with propranolol therapy of 12
      patients suffering vascular hyperplasia of the larynx (subfold hemangioma) is
      analysed. Nine of these children had been given systemic glucocorticoid therapy
      prior to the present study that failed to produce a clinically significant
      effect. On the contrary, the treatment with propranolol resulted in a well
      apparent clinical effect in the form of the marked decrease in the size of
      subfold hemangioma and the reduction in the degree of laryngeal stenosis from
      grade 2-3 to 0-1 as early as 10-14 days after the onset of propranolol therapy at
      a daily dose of 2 mg/kg. None of the patients developed adverse reactions related
      to the treatment with propranolol. The results of the study indicate that the
      treatment of vascular hyperplasia, such as subfold hemangioma with the non
      selective beta-blocker propranolol is both efficacious and safe for the patients.
      This gives reason to recommend this therapeutic modality as the first-line
      treatment of the children starting from the first weeks of life. 

PMID- 24577033
TI  - [The application of essential oils for the treatment of acute rhinitis in the
      breastfed infants].
AB  - Specific features of the clinical course of acute rhinitis in the breastfed
      infants are described in conjunction with the approaches to the treatment of this
      condition. Special attention is given to the possibilities of inhalation of
      essential oils for this purpose. The results of the estimation of the
      effectiveness and tolerability of these substances are discussed with special
      reference to the "Dyshi" composition designed for monotherapy of infectious
      rhinitis in the children during the first year of life. 

PMID- 24577034
TI  - [The use of cone beam computed tomography for diagnostics of chronic suppurative
      otitis media].
AB  - The objective of the present study was to estimate the potential of cone beam
      computed tomography of the temporal bone as a diagnostic tool for chronic
      suppurative otitis media. This method was employed to study the temporal bones of
      33 patients presenting with chronic suppurative otitis media (18 cases of one
      sided and 15 cases of two-sided inflammatory process). The results of the total
      of 48 sessions of beam computed tomography of the temporal bones were available
      for analysis. The age of the patients varied from 16 to 80 years. Seven of them
      presented with chronic suppurative otitis media in combination with
      cholesteatoma. The clinical symptoms of chronic suppurative otitis media were
      revealed by cone beam computed tomography in conjunction with the peculiarities
      of visualization of bone tissue destruction using this technique (both in the
      presence of cholesteatoma and without it). The rationale has been developed for
      the use of cone beam computed tomography in diagnostics of chronic suppurative
      otitis media. 

PMID- 24577035
TI  - [Rational antibacterial therapy of acute inflammatory ENT disorders].
AB  - The present communication is designed to overview the current data on the
      classification, etiology, and treatment of acute inflammatory ENT disorders based
      on the international experience. The results of analysis of on-going studies on
      the effectiveness of antibiotic therapy of acute inflammatory ENT disorders are
      considered. It is concluded that antibiotic therapy is currently the most
      efficacious method for the treatment of the patients presenting with these
      diseases accompanied by purulent discharge and elevated temperature.
      Recommendations on rational antibacterial therapy of acute inflammatory ENT
      disorders are proposed. 

PMID- 24577036
TI  - [Stapedoplasty in a HIV-infected patient].
AB  - This paper reports an observation illustrating the possibility of the successful
      surgical treatment of otosclerosis in a HIV-infected patient presenting with
      acquired immunodeficiency syndrome (AIDS) and positive response in the test for
      hepatitis C. The authors used the results of multispiral computed tomography
      (MSCT) of the temporal bones as a basis for the prediction of the outcome of the
      surgical intervention taking into consideration specific primary manifestations
      of HIV infection as well as immunological and virlogical responses to anti
      retroviral therapy. 

PMID- 24577037
TI  - [The new complex multimedia program for the training in otosurgery].
AB  - The objective of the present study was to develop the complex program for the
      training in otosurgery. The proposed complex program for teaching surgical
      procedures on the ear is described. The program consists of two steps,
      preparation and dissection. The first stage is designed to prepare the learner
      surgeons for dissection with the use of the teaching materials "Manipulations on
      the temporal bone" and the 3D model of the temporal bone. At the second stage,
      the learners perform successively two tasks: dissection of an artificial and
      cadaveric bones with the maximum possible number of surgical procedures on each
      bone. The aforementioned teaching materials and 3D model of the temporal bone are
      used at the dissection stage too. 

PMID- 24577038
TI  - [Optimization of the pedagogical process at the department of
      otorhinolaryngology].
AB  - The objective of the present work was to optimize the educational process with
      respect to teaching otorhinolaryngology based on the experience accumulated in
      this sphere with the use of fundamental management components. Special emphasis
      is laid on the innovative teaching methods employed in the higher education
      institutions for training clinical otorhinolaryngologists. The analysis of the
      functional responsibilities of the academic staff in medical institutions and the
      main components of the educational activity is presented. The basic principles of
      the quality management system are described. The conclusions made by the authors
      concern the possibility of standardization and prognostication in the higher
      education system that can be used for the development of practical guidelines for
      the academic staff. 

PMID- 24577040
TI  - Characterization of human coronavirus OC43 and human coronavirus NL63 infections
      among hospitalized children <5 years of age.
AB  - BACKGROUND: Multiplex molecular assays now make it possible for clinical
      laboratories to detect human coronaviruses (HCoVs). We investigated the clinical
      characteristics of HCoV-OC43 and HCoV-NL63 in patients <5 years of age during a
      recent coronavirus season. METHODS: Respiratory viruses were detected using a
      multiplex molecular assay at St. Louis Children's Hospital starting in November
      2012. We analyzed demographic and clinical data from all patients <5 years of age
      with solo detection of HCoV-OC43 (n = 52) and HCoV-NL63 (n = 44) and for
      comparison, samples of children with respiratory syncytial virus, parainfluenza
      virus and picornaviruses. RESULTS: During the study period, HCoV-OC43 (4%) was
      the 5th and HCoV-NL63 the 8th (2%) most common respiratory virus. Coinfections
      were detected in 35% and 38% of children with HCoV-OC43 and HCoV-NL63,
      respectively. Croup was more common with HCoV-NL63 (30%) than with HCoV-OC43
      (2%). Lower respiratory tract infection occurred in 33% of children with HCoV
      OC43 and 25% of children with HCoV-NL63. Severe illness was less common in HCoV
      NL63, HCoV-OC43 and parainfluenza virus (14%, each) compared with respiratory
      syncytial virus (30%) and picornaviruses (26%; P = 0.055 for HCoVs combined
      compared with the other respiratory viruses) and occurred mainly in those with
      underlying medical conditions. CONCLUSIONS: Infections caused by HCoV-OC43 and
      HCoV-NL63 are common and include some with lower respiratory tract involvement
      and severe disease, especially in children with underlying medical conditions.
      Overall, a substantial burden of disease associated with both HCoV-OC43 and HCoV
      NL63 was observed for hospitalized children <5 years of age.

PMID- 24577039
TI  - Multicenter study of viral etiology and relapse in hospitalized children with
      bronchiolitis.
AB  - BACKGROUND: It is unclear whether the infectious etiology of severe bronchiolitis
      affects short-term outcomes, such as posthospitalization relapse. We tested the
      hypothesis that children hospitalized with rhinovirus (RV) bronchiolitis, either
      as a sole pathogen or in combination with respiratory syncytial virus (RSV), are
      at increased risk of relapse. METHODS: We performed a 16-center, prospective
      cohort study of hospitalized children age <2 years with bronchiolitis. During the
      winters of 2007-2010, researchers collected clinical data and nasopharyngeal
      aspirates from study participants; the aspirates were tested using real-time
      polymerase chain reaction. The primary outcome was bronchiolitis relapse (urgent
      bronchiolitis visit or scheduled visit at which additions to the bronchiolitis
      medications were made) during the 2 weeks after hospital discharge. RESULTS:
      Among 1836 enrolled children with 2-week, follow-up data, the median age was 4
      months and 60% were male. Overall, 48% had sole RSV infection, 8% had sole RV
      infection, and 13% had RSV/RV coinfection. Compared with children with sole RSV
      infection, and adjusting for 10 demographic and clinical characteristics and
      clustering of patients within hospitals, children with sole RV infection did not
      differ in their likelihood of relapse (odds ratio: 0.99; 95% confidence interval:
      0.52-1.90; P = 0.98), whereas those with RSV/RV coinfection were more likely to
      have relapse (odds ratio: 1.54; 95% confidence interval: 1.03-2.30; P = 0.03).
      CONCLUSIONS: In this prospective, multicenter, multiyear study of children
      hospitalized with bronchiolitis, we found that RSV/RV coinfection was
      independently associated with a higher likelihood of bronchiolitis relapse.
      Present data support the concept that the infectious etiology of severe
      bronchiolitis affects short-term outcomes.

PMID- 24577041
TI  - Risk factors for critical disease and death from hand, foot and mouth disease.
AB  - BACKGROUND: There has been a high mortality and morbidity rate of critical and
      fatal patients from hand, foot and mouth disease (HFMD) in China in recent.
      Causes for development of critical and fatal disease remain unclear. METHODS: We
      performed a case-control study to assess the association between use of drugs and
      development of critical disease and death from HFMD. RESULTS: We found that
      glucocorticoids treatment was associated with a greater incidence of severe HFMD,
      whereas andrographolides treatment was associated with a protective effect when
      they are used for treatment within 48 hours after onset or before being diagnosed
      as critical. CONCLUSIONS: We recommend that glucocorticoids should not be used
      for mild HFMD and andrographolides should undergo clinical trials for treatment
      of enterovirus 71 infections.

PMID- 24577043
TI  - Changes in alpha1-adrenoceptor and NGF/proNGF pathway: a possible mechanism in
      diabetic urethral dysfunction.
AB  - OBJECTIVE: To investigate the changes in the alpha1-adrenoceptor and nerve growth
      factor (NGF)/NGF precursor (proNGF) pathway in the urethra after diabetes
      induction. MATERIALS AND METHODS: Urethral relaxation function was determined by
      simultaneous recordings of intravesical pressure under isovolumetric conditions
      and urethral perfusion pressure (UPP) in diabetic rats. The expression of alpha1
      adrenoceptor, NGF, proNGF, low-affinity p75 receptor for neurotrophins (p75(NTR))
      and sortilin in the urethras was measured using real-time quantitative polymerase
      chain reaction (RT-qPCR), enzyme-linked immunosorbent assay and Western blotting.
      RESULTS: In diabetic rats, the lowest urethral pressure (UPP nadir) during
      urethral relaxation was significantly higher. Intravenous administration of
      tamsulosin, an alpha1-adrenoceptor antagonist, significantly decreased the UPP
      nadir and baseline UPP in diabetic rats. RT-qPCR and Western blotting studies
      showed a statistically significant increase of alpha1a- and alpha1b-adrenoceptor
      in the urethras from the diabetic group (p < 0.05). The expression of NGF was
      significantly decreased in the urethras from the diabetic group while the
      expression of proNGF was significantly increased (p < 0.05). The p75(NTR) level
      in the urethras of diabetic rats was decreased compared with controls (p < 0.05)
      and there was no significant difference regarding sortilin between the two groups
      (p > 0.05). CONCLUSION: This study validated the diabetic urethral dysfunction
      and furthermore indicated that the increase in the expression of alpha1
      adrenoceptor and changes in the NGF/proNGF pathway may be involved in diabetic
      urethral dysfunction.

PMID- 24577042
TI  - The burden of influenza hospitalizations in infants from 2003 to 2012, United
      States.
AB  - BACKGROUND: Little information is available describing the epidemiology and
      clinical characteristics of those <12 months hospitalized with influenza,
      particularly at a population level. METHODS: We used population-based, laboratory
      confirmed influenza hospitalization surveillance data from 2003 to 2012 seasons
      to describe the impact of influenza by age category (<3, 3 to <6 and 6 to <12
      months). Logistic regression was used to explore risk factors for intensive care
      unit (ICU) admission. Adjusted age-specific, influenza-associated hospitalization
      rates were calculated and applied to the number of US infants to estimate
      national numbers of hospitalizations. RESULTS: Influenza was associated with an
      annual average of 6514 infant hospitalizations (range 1842-12,502).
      Hospitalization rates among infants <3 months were substantially higher than the
      rate in older infants. Most hospitalizations occurred in otherwise healthy
      infants (75%) among whom up to 10% were admitted to the ICU and up to 4% had
      respiratory failure. These proportions were 2-3 times higher in infants with high
      risk conditions. Infants <6 months were 40% more likely to be admitted to the ICU
      than older infants. Lung disease (adjusted odds ratio 1.80; 95% confidence
      interval 1.22-2.67), cardiovascular disease (adjusted odds ratio: 4.16; 95%
      confidence interval: 2.65-6.53), and neuromuscular disorder (adjusted odds ratio:
      2.99; 95% confidence interval: 1.87-4.78) were risk factors for ICU admission
      among all infants. CONCLUSIONS: The impact of influenza on infants, particularly
      those very young or with high risk conditions, underscores the importance of
      influenza vaccination, especially among pregnant women and those in contact with
      young infants not eligible for vaccination.

PMID- 24577045
TI  - Understanding the effect of vibrational excitation in reaction dynamics: the Ne +
      H2(+)(v = 0-17, j = 1) -> NeH(+) + H, Ne + H(+) + H proton transfer and
      dissociation cross sections.
AB  - The dependence of the cross section (sigma) of the Ne + H2(+)-> NeH(+) + H proton
      transfer reaction on the vibrational excitation of H2(+), v = 0-17 and j = 1, was
      analyzed in detail at the collision energies (Ecol) of 0.7 and 1.7 eV, using the
      quasi-classical trajectory (QCT) method and the PHHJ3 and LZHH potential energy
      surfaces (PESs), taking advantage of the rich experimental data available for
      this reaction as a function of H2(+)(v). The efficiency of vibrational excitation
      to promote the reaction was investigated from the analysis of the sigma(QCT) vs.
      v dependence in terms of the average reaction probability, maximum impact
      parameter, regions of the (late barrier) PES explored, and taking into account
      the Ne + H2(+)-> Ne + H(+) + H dissociative channel, which plays a dominant role
      at high enough total energies. Although the earlier PHHJ3 PES performs rather
      well, the LZHH PES QCT results show a better agreement with the experiment. On
      the other hand, some artifacts were found in recently reported QCT calculations
      (unphysical oscillations in sigma(QCT) as a function of v), and the present study
      shows that special care is needed when carrying out QCT calculations involving
      highly excited vibrational states. 

PMID- 24577044
TI  - Regulation of human telomerase splicing by RNA:RNA pairing.
AB  - Telomerase adds telomeric repeats onto chromosome ends and is almost universally
      upregulated in human cancers. Here we demonstrate that RNA:RNA pairing regulates
      splicing of the catalytic subunit of human telomerase (TERT). Human alleles
      contain a variable number of 38 bp repeats within TERT intron 6 (>1 kb from exon
      intron junctions). At least nine repeats are required for generating the major
      non-functional 'minus beta' isoform, which skips exons 7 and 8. RNA:RNA pairing
      between the repeats and the pre-mRNA might bring exons 6 and 9 closer, thereby
      promoting exon skipping. To demonstrate this, we show that mutations within the
      repeat that abolish exon skipping are corrected by compensatory mutations in the
      pre-mRNA. This study thus identifies RNA:RNA pairing by repetitive sequences as a
      novel form of alternative splicing regulation in a gene crucial for cancer
      survival and sheds new light on functional roles for short repetitive sequences
      embedded deep within introns throughout the genome.

PMID- 24577046
TI  - Preanalysis storage conditions influence the measurement of brain-derived
      neurotrophic factor levels in peripheral blood.
AB  - BACKGROUND: Brain-derived neurotrophic factor (BDNF) is a neurotrophin that plays
      a pivotal role in regulating neuronal function throughout life, and this factor
      is regarded as a potential biomarker of mental disorders. However, previous
      studies have suggested that plasma BDNF levels are more variable than serum BDNF
      levels. METHODS: We determined the influence of time and temperature on the
      measurement of peripheral blood BDNF levels. Blood samples were aliquoted into
      four types of tubes, including tubes containing heparin,
      ethylenediaminetetraacetic acid (EDTA), and citrate for plasma, and anticoagulant
      free tubes for serum. The samples were stored at 4 or 25 degrees C for 0, 1, 2,
      4, 6, 24 or 48 h, and the plasma and serum BDNF levels were measured using enzyme
      linked immunosorbent assay. RESULTS: There were interindividual and
      interanticoagulant compound variability in the plasma BDNF levels. The measured
      plasma BDNF levels increased over time, whereas the serum BDNF levels remained
      unchanged. Furthermore, the BDNF levels detected in plasma stored in heparin
      tubes at 4 degrees C and those for samples stored in EDTA tubes at 25 degrees C
      were much higher than those of the other samples. CONCLUSION: This study
      indicates that measurements of plasma BDNF levels are dependent not only on the
      anticoagulant compounds but also on the storage time and temperature conditions
      used after blood sampling.

PMID- 24577047
TI  - Paternal age at childbearing and offspring psychiatric and academic morbidity.
AB  - IMPORTANCE: Advancing paternal age is associated with increased genetic mutations
      during spermatogenesis, which research suggests may cause psychiatric morbidity
      in the offspring. The effects of advancing paternal age at childbearing on
      offspring morbidity remain unclear, however, because of inconsistent
      epidemiologic findings and the inability of previous studies to rigorously rule
      out confounding factors. OBJECTIVE: To examine the associations between advancing
      paternal age at childbearing and numerous indexes of offspring morbidity. DESIGN,
      SETTING, AND PARTICIPANTS: We performed a population-based cohort study of all
      individuals born in Sweden in 1973-2001 (N = 2,615,081), with subsets of the data
      used to predict childhood or adolescent morbidity. We estimated the risk of
      psychiatric and academic morbidity associated with advancing paternal age using
      several quasi-experimental designs, including the comparison of differentially
      exposed siblings, cousins, and first-born cousins. EXPOSURE: Paternal age at
      childbearing. MAIN OUTCOMES AND MEASURES: Psychiatric (autism, attention
      deficit/hyperactivity disorder, psychosis, bipolar disorder, suicide attempt, and
      substance use problem) and academic (failing grades and low educational
      attainment) morbidity. RESULTS: In the study population, advancing paternal age
      was associated with increased risk of some psychiatric disorders (eg, autism,
      psychosis, and bipolar disorders) but decreased risk of the other indexes of
      morbidity. In contrast, the sibling-comparison analyses indicated that advancing
      paternal age had a dose-response relationship with every index of morbidity, with
      the magnitude of the associations being as large or larger than the estimates in
      the entire population. Compared with offspring born to fathers 20 to 24 years
      old, offspring of fathers 45 years and older were at heightened risk of autism
      (hazard ratio [HR] = 3.45; 95% CI, 1.62-7.33), attention-deficit/hyperactivity
      disorder (HR = 13.13; 95% CI, 6.85-25.16), psychosis (HR = 2.07; 95% CI, 1.35
      3.20), bipolar disorder (HR = 24.70; 95% CI, 12.12-50.31), suicide attempts (HR =
      2.72; 95% CI, 2.08-3.56), substance use problems (HR = 2.44; 95% CI, 1.98-2.99),
      failing a grade (odds ratio [OR] = 1.59; 95% CI, 1.37-1.85), and low educational
      attainment (OR = 1.70; 95% CI, 1.50-1.93) in within-sibling comparisons.
      Additional analyses using several quasi-experimental designs obtained
      commensurate results, further strengthening the internal and external validity of
      the findings. CONCLUSIONS AND RELEVANCE: Advancing paternal age is associated
      with increased risk of psychiatric and academic morbidity, with the magnitude of
      the risks being as large or larger than previous estimates. These findings are
      consistent with the hypothesis that new genetic mutations that occur during
      spermatogenesis are causally related to offspring morbidity.

PMID- 24577050
TI  - Ocean acidification impairs vermetid reef recruitment.
AB  - Vermetids form reefs in sub-tropical and warm-temperate waters that protect
      coasts from erosion, regulate sediment transport and accumulation, serve as
      carbon sinks and provide habitat for other species. The gastropods that form
      these reefs brood encapsulated larvae; they are threatened by rapid environmental
      changes since their ability to disperse is very limited. We used transplant
      experiments along a natural CO2 gradient to assess ocean acidification effects on
      the reef-building gastropod Dendropoma petraeum. We found that although D.
      petraeum were able to reproduce and brood at elevated levels of CO2, recruitment
      success was adversely affected. Long-term exposure to acidified conditions
      predicted for the year 2100 and beyond caused shell dissolution and a significant
      increase in shell Mg content. Unless CO2 emissions are reduced and conservation
      measures taken, our results suggest these reefs are in danger of extinction
      within this century, with significant ecological and socioeconomic ramifications
      for coastal systems. 

PMID- 24577051
TI  - Protective effect of Vaccinium myrtillus extract against UVA- and UVB-induced
      damage in a human keratinocyte cell line (HaCaT cells).
AB  - Recently, the field of skin protection have shown a considerable interest in the
      use of botanicals. Vaccinium myrtillus contains several polyphenols and
      anthocyanins with multiple pharmacological properties. The purpose of our study
      was to examine whether a water-soluble V. myrtillus extract (dry matter 12.4%;
      total polyphenols 339.3mg/100 g fw; total anthocyanins 297.4 mg/100 g fw) was
      able to reduce UVA- and UVB-induced damage using a human keratinocyte cell line
      (HaCaT). HaCaT cells were pretreated for 1h with extract in a serum-free medium
      and then irradiated with UVA (8-40 J/cm(2)) and UVB (0.008-0.72 J/cm(2)) rays.
      All experiments were performed 24h after the end of irradiation, except for
      oxidative stress tests. The extract was able to reduce the UVB-induced
      cytotoxicity and genotoxicity (studied by comet and micronucleous assays) at
      lower doses. V. myrtillus extract reduced lipid peroxidation UVB-induced, but had
      no effect against the ROS UVB-produced. With UVA-induced damage V. myrtillus
      reduced genotoxicity as well as the unbalance of redox intracellular status.
      Moreover our extract reduced the UVA-induced apoptosis, but had no effect against
      the UVB one. V. myrtillus extract showed its free radical scavenging properties
      reducing oxidative stress and apoptotic markers, especially in UVA-irradiated
      cells.

PMID- 24577052
TI  - Highly conductive and flexible polymer composites with improved mechanical and
      electromagnetic interference shielding performances.
AB  - New flexible and conductive materials (FCMs) comprising a quartz fiber cloth
      (QFC) reinforced multi-walled carbon nanotubes (MWCNTs)-carbon aerogel (QMCA) and
      poly(dimethylsiloxane) (PDMS) have been successfully prepared. The QMCA-PDMS
      composite with a very low loading of MWCNTs (~1.6 wt%) demonstrates enhanced
      performance in tensile strength (129.6 MPa), modulus (3.41 GPa) and
      electromagnetic interference (EMI) shielding efficiency (SE) (~16 dB in X-band
      (8.2-12.4 GHz) region). Compared to the QC (where MWCNTs were simply deposited on
      the QFCs without forming aerogel networks) based PDMS composite, a ~120%, 330%
      and 178% increase of tensile strength, modulus, and EMI SE was obtained,
      respectively. Moreover, the EMI SE of the QMCA-PDMS composite can further reach
      20 dB (a SE level needed for commercial applications) with only 2 wt% MWCNTs.
      Furthermore, the conductivity of the QMCA-PDMS laminate can reach 1.67 S cm(-1)
      even with very low MWCNTs (1.6 wt%), which still remains constant even after 5000
      times bending and exhibits an increase of ~170% than that of MWCNT-carbon aerogel
      (MCA)-PDMS at 20% strain. Such intriguing performances are mainly attributed to
      their unique networks in QMCA-PDMS composites. In addition, these features can
      also protect electronics against harm from external forces and EMI, giving the
      brand-new FCMs huge potential in next-generation devices, like E-skin, robot
      joints and so on. 

PMID- 24577053
TI  - Organization of the serotonergic system in the central nervous system of two
      basal actinopterygian fishes: the Cladistians Polypterus senegalus and
      Erpetoichthys calabaricus.
AB  - Cladistians (Polypteriformes) are currently considered basal to other living ray
      finned fishes (actinopterygians), and their brain organization is therefore
      critical to providing information about the primitive neural characters that
      existed in the earliest ray-finned fishes. The organization of the serotonergic
      system in the brain has been carefully analyzed in most vertebrate groups, and in
      the present study we provide the first detailed information on the distribution
      of serotonergic cell bodies and fibers in the central nervous system of
      representative species of the two extant genera of cladistians, i.e. Polypterus
      senegalus and Erpetoichthys calabaricus, by means of immunohistochemistry against
      serotonin (5-HT). Distinct groups of immunoreactive cells were detected in the
      preoptic area, the hypothalamic paraventricular organ, the pineal organ, the
      pretectal region, the long column of the raphe in the rhombencephalic midline,
      the spinal cord, and amacrine cells in the inner nuclear layer of the retina.
      Fiber labeling was widely distributed in all main brain subdivisions but was more
      abundant in distinct pallial and subpallial areas, the preoptic area, the
      thalamus, the optic tectum, the tori semicircularis and lateralis, the
      rhombencephalic reticular formation, the nucleus of the solitary tract, and the
      dorsal aspect of the spinal cord. Our analysis makes it possible to establish
      which serotonergic structures characterized the earliest ray-finned fishes, and a
      comparison of these results with those from other classes of vertebrates,
      including a segmental analysis to correlate cell populations, reveals that most
      characteristics, such as the presence of serotonergic cells in the preoptic area
      and the basal hypothalamus, are preserved in all anamniotes. However, this system
      seems to be reduced in amniotes, mainly mammals, although important features are
      shared, such as the presence of serotonergic cells in the pineal organ, the
      retina, and the raphe nuclei.

PMID- 24577054
TI  - Comment on 'The latency period of mesothelioma among a cohort of British asbestos
      workers (1978-2005)'.

PMID- 24577055
TI  - Clinicopathological and prognostic significance of interleukin-8 expression and
      its relationship to KRAS mutation in lung adenocarcinoma.
AB  - BACKGROUND: On the basis of our recent findings of oncogenic KRAS-induced
      interleukin-8 (IL-8) overexpression in non-small cell lung cancer, we assessed
      the clinicopathological and prognostic significances of IL-8 expression and its
      relationship to KRAS mutations in lung adenocarcinomas. METHODS: IL-8 expression
      was examined by quantitative RT-PCR using 136 of surgical specimens from lung
      adenocarcinoma patients. The association between IL-8 expression,
      clinicopathological features, KRAS or EGFR mutation status and survival was
      analysed. RESULTS: IL-8 was highly expressed in tumours from elderly patients or
      smokers and in tumours with pleural involvement or vascular invasion. In a non
      smokers' subgroup, IL-8 level positively correlated with age. IL-8 was highly
      expressed in tumours with KRAS mutations compared with those with EGFR mutations
      or wild-type EGFR/KRAS. Lung adenocarcinoma patients with high IL-8 showed
      significantly shorter disease-free survival (DFS) and overall survival (OS) than
      those with low IL8. DFS and OS were significantly shorter in the patients with
      mutant KRAS/high IL-8 than in those with wild-type KRAS/low IL-8. Cox regression
      analyses demonstrated that elevated IL-8 expression correlated with unfavourable
      prognosis. CONCLUSIONS: Our findings suggest that IL-8 expression is associated
      with certain clinicopathological features including age and is a potent
      prognostic marker in lung adenocarcinoma, especially in oncogenic KRAS-driven
      adenocarcinoma.

PMID- 24577056
TI  - Identifying microRNAs regulating B7-H3 in breast cancer: the clinical impact of
      microRNA-29c.
AB  - BACKGROUND: B7-H3, an immunoregulatory protein, is overexpressed in several
      cancers and is often associated with metastasis and poor prognosis. Here, our aim
      was to identify microRNAs (miRNAs) regulating B7-H3 and assess their potential
      prognostic implications in breast cancer. METHODS: MicroRNAs targeting B7-H3 were
      identified by transfecting two breast cancer cell lines with a library of 810
      miRNA mimics and quantifying changes of B7-H3 protein levels using protein lysate
      microarrays. For validations we used western immunoblotting and 3'-UTR luciferase
      assays. Clinical significance of the miRNAs was assayed by analysing whether
      their expression levels correlated with outcome in two cohorts of breast cancer
      patients (142 and 81 patients). RESULTS: We identified nearly 50 miRNAs that
      downregulated B7-H3 protein levels. Western immunoblotting validated the impact
      of the 20 most effective miRNAs. Thirteen miRNAs (miR-214, miR-363*, miR-326, miR
      940, miR-29c, miR-665, miR-34b*, miR-708, miR-601, miR-124a, miR-380-5p, miR-885
      3p, and miR-593) targeted B7-H3 directly by binding to its 3'-UTR region.
      Finally, high expression of miR-29c was associated with a significant reduced
      risk of dying from breast cancer in both cohorts. CONCLUSIONS: We identified
      miRNAs efficiently downregulating B7-H3 expression. The expression of miR-29c
      correlated with survival in breast cancer patients, suggesting a tumour
      suppressive role for this miRNA.

PMID- 24577057
TI  - Lack of correlation of stem cell markers in breast cancer stem cells.
AB  - BACKGROUND: Various markers are used to identify the unique sub-population of
      breast cancer cells with stem cell properties. Whether these markers are
      expressed in all breast cancers, identify the same population of cells, or equate
      to therapeutic response is controversial. METHODS: We investigated the expression
      of multiple cancer stem cell markers in human breast cancer samples and cell
      lines in vitro and in vivo, comparing across and within samples and relating
      expression with growth and therapeutic response to doxorubicin, docetaxol and
      radiotherapy. RESULTS: CD24, CD44, ALDH and SOX2 expression, the ability to form
      mammospheres and side-population cells are variably present in human cancers and
      cell lines. Each marker identifies a unique rather than common population of
      cancer cells. In vivo, cells expressing these markers are not specifically
      localized to the presumptive stem cell niche at the tumour/stroma interface.
      Repeated therapy does not consistently enrich cells expressing these markers,
      although ER-negative cells accumulate. CONCLUSIONS: Commonly employed methods
      identify different cancer cell sub-populations with no consistent therapeutic
      implications, rather than a single population of cells. The relationships of
      breast cancer stem cells to clinical parameters will require identification of
      specific markers or panels for the individual cancer.

PMID- 24577059
TI  - Confronting the stigma of opioid use disorder--and its treatment.

PMID- 24577058
TI  - A new domain in the Toll/IL-1R domain-containing adaptor inducing interferon-beta
      factor protein amino terminus is important for tumor necrosis factor-alpha
      receptor-associated factor 3 association, protein stabilization and interferon
      signaling.
AB  - Toll/IL-1R domain-containing adaptor inducing interferon-beta (IFN-beta) factor
      (TRIF) is a key adaptor for Toll-like receptor (TLR) 3 and TLR4 signaling. Using
      a novel cDNA isolate encoding a TRIF protein with a 21-residue deletion (Delta160
      181) from its amino-terminal half, we investigated the impact of this deletion on
      TRIF functions. Transfection studies consistently showed higher expression levels
      of the (Delta160-181) TRIF compared to wild-type (wt) TRIF, an effect unrelated
      to apoptosis, cell lines or plasmid amplification. Colocalization of wt and
      (Delta160-181) TRIF proteins led to a dramatic reduction of their respective
      expressions, suggesting that wt/(Delta160-181) TRIF heterocomplexes are targeted
      for degradation. We demonstrated that wt TRIF associates with tumor necrosis
      factor-alpha receptor-associated factor 3 (TRAF3) better than (Delta160-181)
      TRIF, culminating in its greater ubiquitination and proteolysis. This explains,
      in part, the differential expression levels of the two TRIF proteins. Despite
      higher expression levels in transfected cells, (Delta160-181) TRIF inefficiently
      transactivated the IFN pathway, whereas the nuclear factor-kappaB (NF-kappaB)
      pathway activation remained similar to that by wt TRIF. In coexpression studies,
      (Delta160-181) TRIF marginally contributed to the IFN pathway activation, but
      still enhanced NF-kappaB signaling with wt TRIF. Therefore, this 21 amino acid
      sequence is crucial for TRAF3 association, modulation of TRIF stability and
      activation of the IFN pathway.

PMID- 24577060
TI  - Evidence that transient changes in sudomotor output with cold and warm fluid
      ingestion are independently modulated by abdominal, but not oral thermoreceptors.
AB  - Two studies were performed to 1) characterize changes in local sweat rate (LSR)
      following fluid ingestion of different temperatures during exercise, and 2)
      identify the potential location of thermoreceptors along the gastrointestinal
      tract that independently modify sudomotor activity. In study 1, 12 men cycled at
      50% Vo2peak for 75 min while ingesting 3.2 ml/kg of 1.5 degrees C, 37 degrees C,
      or 50 degrees C fluid 5 min before exercise; and after 15, 30, and 45-min of
      exercise. In study 2, 8 men cycled at 50% Vo2peak for 75 min while 3.2 ml/kg of
      1.5 degrees C or 50 degrees C fluid was delivered directly into the stomach via a
      nasogastric tube (NG trials) or was mouth-swilled only (SW trials) after 15, 30,
      and 45 min of exercise. Rectal (Tre), aural canal (Tau), and mean skin
      temperature (Tsk); and LSR on the forehead, upper-back, and forearm were
      measured. In study 1, Tre, Tau, and Tsk were identical between trials, but after
      each ingestion, LSR was significantly suppressed at all sites with 1.5 degrees C
      fluid and was elevated with 50 degrees C fluid compared with 37 degrees C fluid
      (P < 0.001). The peak difference in mean LSR between 1.5 degrees C and 50 degrees
      C fluid after ingestion was 0.29 +/- 0.06 mg.min(-1).cm(-2). In study 2, LSR was
      similar between 1.5 degrees C and 50 degrees C fluids with SW trials (P = 0.738),
      but lower at all sites with 1.5 degrees C fluid in NG trials (P < 0.001) despite
      no concurrent differences in Tre, Tau, and Tsk. These data demonstrate that 1)
      LSR is transiently altered by cold and warm fluid ingestion despite similar core
      and skin temperatures; and 2) thermoreceptors that independently and acutely
      modulate sudomotor output during fluid ingestion probably reside within the
      abdominal area, but not the mouth. 

PMID- 24577061
TI  - Skeletal muscle capillary density and microvascular function are compromised with
      aging and type 2 diabetes.
AB  - Adequate muscle perfusion is required for the maintenance of skeletal muscle
      mass. Impairments in microvascular structure and/or function with aging and type
      2 diabetes have been associated with the progressive loss of skeletal muscle
      mass. Our objective was to compare muscle fiber type specific capillary density
      and endothelial function between healthy young men, healthy older men, and age
      matched type 2 diabetes patients. Fifteen healthy young men (24 +/- 1 yr), 15
      healthy older men (70 +/- 2 yr), and 15 age-matched type 2 diabetes patients (70
      +/- 1 yr) were selected to participate in the present study. Whole body insulin
      sensitivity, muscle fiber type specific capillary density, sublingual
      microvascular density, and dimension of the erythrocyte-perfused boundary region
      were assessed to evaluate the impact of aging and/or type 2 diabetes on
      microvascular structure and function. Whole body insulin sensitivity was
      significantly lower at a more advanced age, with lowest values reported in the
      type 2 diabetic patients. In line, skeletal muscle capillary contacts were much
      lower in the older and older type 2 diabetic patients when compared with the
      young. Sidestream darkfield imaging showed a significantly greater thickness of
      the erythrocyte perfused boundary region in the type 2 diabetic patients compared
      with the young. Skeletal muscle capillary density is reduced with aging and type
      2 diabetes and accompanied by impairments in endothelial glycocalyx function,
      which is indicative of compromised vascular function. 

PMID- 24577063
TI  - Catalysis for biomass and CO2 use through solar energy: opening new scenarios for
      a sustainable and low-carbon chemical production.
AB  - The use of biomass, bio-waste and CO2 derived raw materials, the latter
      synthesized using H2 produced using renewable energy sources, opens new scenarios
      to develop a sustainable and low carbon chemical production, particularly in
      regions such as Europe lacking in other resources. This tutorial review discusses
      first this new scenario with the aim to point out, between the different possible
      options, those more relevant to enable this new future scenario for the chemical
      production, commenting in particular the different drivers (economic,
      technological and strategic, environmental and sustainability and socio
      political) which guide the selection. The case of the use of non-fossil fuel
      based raw materials for the sustainable production of light olefins is discussed
      in more detail, but the production of other olefins and polyolefins, of drop-in
      intermediates and other platform molecules are also analysed. The final part
      discusses the role of catalysis in establishing this new scenario, summarizing
      the development of catalysts with respect to industrial targets, for (i) the
      production of light olefins by catalytic dehydration of ethanol and by CO2
      conversion via FTO process, (ii) the catalytic synthesis of butadiene from
      ethanol, butanol and butanediols, and (iii) the catalytic synthesis of HMF and
      its conversion to 2,5-FDCA, adipic acid, caprolactam and 1,6-hexanediol. 

PMID- 24577064
TI  - Prognostic indicators for children and young people at the end of life: A Delphi
      study.
AB  - BACKGROUND: Recognizing transitions in end of life care for children is difficult
      and hinders communication and care planning. AIM: To identify the signs and
      symptoms that are most useful in signalling which children may have end of life
      care needs. METHODS: A Delphi study was undertaken with palliative care
      professionals who rated the extent to which 75 symptoms alerted them that a
      child/young person may have moved into his or her last (a) weeks/days, (b) 6-12
      months of life using a 7-point response scale. Level of support for items was
      indicated by the median, and consensus was shown by the mean absolute deviation
      from the median. The impact of the Delphi on final agreement and consensus was
      also assessed. RESULTS: Second-round questionnaires were completed by 49 (89%)
      individuals. It was easier to identify prognostic items in the last weeks/days
      than earlier in the end of life trajectory. Items most indicative included
      failure of physiological systems, deteriorating level of consciousness, loss of
      autonomic control (e.g. breathing and peripheral circulation), together with a
      feeling of the professional that life is ending and an agreement that
      resuscitation would be futile. Items most indicative of last 6/12 months suggest
      a progressive decline in disease trajectory, increased chest infections or other
      complications from which the child has difficulty in making a full recovery and
      which may require high dependency or critical care. CONCLUSION: This study
      provides important insight into which signs and symptoms are considered most
      valuable in identifying children approaching the end of the life.

PMID- 24577062
TI  - Reduced hepatic eNOS phosphorylation is associated with NAFLD and type 2 diabetes
      progression and is prevented by daily exercise in hyperphagic OLETF rats.
AB  - We tested the hypothesis that nonalcoholic fatty liver disease (NAFLD) is
      associated with reduced hepatic endothelial nitric oxide synthase (eNOS)
      activation status via S1177 phosphorylation (p-eNOS) and is prevented by daily
      voluntary wheel running (VWR). Hyperphagic Otsuka Long-Evans Tokushima Fatty
      (OLETF) rats, an established model of obesity, type 2 diabetes (T2D) and NAFLD,
      and normophagic controls [Long-Evans Tokushima Otsuka (LETO)] were studied at 8,
      20, and 40 wk of age. Basal hepatic eNOS phosphorylation (p-eNOS/eNOS) was
      similar between LETO and OLETFs with early hepatic steatosis (8 wk of age) and
      advanced steatosis, hyperinsulinemia, and hyperglycemia (20 wk of age). In
      contrast, hepatic p-eNOS/eNOS was significantly lower (P < 0.05) in OLETF rats
      with T2D advancement and the transition to more advanced NAFLD with inflammation
      and fibrosis [increased tumor necrosis factor-alpha (TNF-alpha), CD68, and CD163
      mRNA expression; 40 wk of age]. Reduced hepatic eNOS activation status in 40-wk
      OLETF rats was significantly correlated with reduced p-Akt/Akt (r = 0.73, P <
      0.05), reduced serum insulin (r = 0.59, P < 0.05), and elevated serum glucose (r
      = -0.78, P < 0.05), suggesting a link between impaired glycemic control and
      altered hepatic nitric oxide metabolism. VWR by OLETF rats, in conjunction with
      NAFLD and T2D prevention, normalized p-eNOS/eNOS and p-Akt/Akt to LETO levels.
      Basal activation of hepatic eNOS and Akt are maintained until advanced NAFLD and
      T2D development in obese OLETF rats. The prevention of this reduction by VWR may
      result from maintained insulin sensitivity and glycemic control. 

PMID- 24577066
TI  - Borderline personality disorder, neuroscience and responsibility.

PMID- 24577065
TI  - A multisite randomized controlled trial on time to self-support among sickness
      absence beneficiaries. The Danish national return-to-work programme.
AB  - BACKGROUND: In 2010, the Danish Government launched the Danish national return-to
      work (RTW) programme to reduce sickness absence and promote labour market
      attainment. Multidisciplinary teams delivered the RTW programme, which comprised
      a coordinated, tailored and multidisciplinary effort (CTM) for sickness absence
      beneficiaries at high risk for exclusion from the labour market. The aim of this
      article was to evaluate the effectiveness of the RTW programme on self-support.
      METHODS: Beneficiaries from three municipalities (denoted M1, M2 and M3)
      participated in a randomized controlled trial. We randomly assigned beneficiaries
      to CTM (M1: n = 598; M2: n = 459; M3: n = 331) or to ordinary sickness absence
      management (OSM) (M1: n = 393; M2: n = 324; M3: n = 95). We used the Cox
      proportional hazards model to estimate hazard ratios (HR) comparing rates of
      becoming self-supporting between beneficiaries receiving CTM and OSM. RESULTS: In
      M2, beneficiaries from employment receiving CTM became self-supporting faster
      compared with beneficiaries receiving OSM (HR = 1.32, 95% CI: 1.08-1.61). In M3,
      beneficiaries receiving CTM became self-supporting slower than beneficiaries
      receiving OSM (HR = 0.72, 95% CI: 0.54-0.95). In M1, we found no difference
      between the two groups (HR = 0.99, 95% CI: 0.84-1.17). CONCLUSION: The effect of
      the CTM programme on return to self-support differed substantially across the
      three participating municipalities. Thus, generalizing the study results to other
      Danish municipalities is not warranted. TRIAL REGISTRATION: ISRCTN43004323.

PMID- 24577067
TI  - ICD-11 and operationalism: response.

PMID- 24577068
TI  - Plasmon scattering from holes: from single hole scattering to Young's experiment.
AB  - In this paper, the scattering of surface plasmon polaritons (SPPs) into photons
      at holes is investigated. A local, electrically excited source of SPPs using a
      scanning tunneling microscope (STM) produces an outgoing circular plasmon wave on
      a thick (200 nm) gold film on glass containing holes of 250, 500 and 1000 nm
      diameter. Fourier plane images of the photons from hole-scattered plasmons show
      that the larger the hole diameter, the more directional the scattered radiation.
      These results are confirmed by a model where the hole is considered as a
      distribution of horizontal dipoles whose relative amplitudes, directions, and
      phases depend linearly on the local SPP electric field. An SPP-Young's experiment
      is also performed, where the STM-excited SPP wave is incident on a pair of 1 MUm
      diameter holes in the thick gold film. The visibility of the resulting fringes in
      the Fourier plane is analyzed to show that the polarization of the electric field
      is maintained when SPPs scatter into photons. From this SPP-Young's experiment,
      an upper bound of ~200 nm for the radius of this STM-excited source of surface
      plasmon polaritons is determined.

PMID- 24577069
TI  - Implication of P-glycoprotein in formation of depression-prone personality:
      association study between the C3435T MDR1 gene polymorphism and interpersonal
      sensitivity.
AB  - BACKGROUND AND AIM: Interpersonal sensitivity is defined as undue and excessive
      awareness of, and sensitivity to, the behavior and feelings of others. Previous
      studies suggested that interpersonal sensitivity is one of the vulnerable factors
      to depression, and that genetic factors and cortisol are involved in the
      formation of interpersonal sensitivity. On the other hand, P-glycoprotein, which
      is encoded by the multidrug resistance 1 (MDR1) gene, serves as a barrier to
      entry and as an active eliminator for xenobiotics and cellular metabolites
      including cortisol, which is implicated in multiple brain functions. In the
      present study, we examined the effects of the MDR1 C3435T polymorphism
      (rs1045642) on interpersonal sensitivity in healthy subjects. METHODS: The
      subjects were 842 healthy Japanese volunteers (mean age = 26.7 years, male/female
      ratio = 490/352). The C3435T polymorphism of MDR1 gene was detected by a PCR
      method, and interpersonal sensitivity was assessed by the Interpersonal
      Sensitivity Measure (IPSM). RESULTS: The 2-factor analysis of covariance (ANCOVA)
      showed a significant main effect of the MDR1 genotype on the IPSM scores with a
      significant interaction between the genotype and gender. The subsequent 1-factor
      ANCOVA showed that in females the C/C genotype group had higher IPSM scores than
      the C/T genotype group (p < 0.001) and the T/T genotype group (p < 0.001), and
      the C/T genotype group had higher IPSM scores than the T/T genotype group (p =
      0.014). In males no significant association was found between the MDR1 genotype
      and the IPSM scores. In allelic analyses using the chi(2) tests, the C allele
      frequency in females was significantly higher (p < 0.001) in the high IPSM group
      than in the low IPSM group, while there was no significant difference in the C
      allele frequency between the high and low IPSM groups in total subjects and
      males. CONCLUSION: The present study suggests that the C3435T polymorphism of the
      MDR1 gene affects the formation of a depression-prone personality trait in
      Japanese females.

PMID- 24577072
TI  - Corticosteroid-induced meningococcal meningitis in a patient with chronic
      meningococcemia.
AB  - IMPORTANCE: Although chronic meningococcemia is an uncommon disorder, it is of
      great importance to clinicians across multiple disciplines because it presents
      similarly to reactive, neoplastic, or rheumatic disorders. Ruling out chronic
      meningococcemia, however, represents a diagnostic challenge because routine
      microbiological investigations frequently fail to identify Neisseria
      meningitidis. Although treatment with corticosteroids might be helpful in various
      conditions, corticosteroid treatment may lead to severe complications in
      underlying chronic meningococcemia. OBSERVATIONS: We describe a patient with a
      history of recurrent fever, arthralgia, and disseminated skin lesions. The
      patient was assumed to have Sweet syndrome and was treated with corticosteroids.
      Subsequently the patient developed meningococcal meningitis and was admitted to
      the neurointensive care unit. Chronic meningococcemia was confirmed
      retrospectively by nonroutine polymerase chain reaction and silver staining of
      skin biopsy specimens. Immunologic workup revealed decreased IgG subclass 3.
      CONCLUSIONS AND RELEVANCE: Consideration of chronic meningococcemia is important
      when a patient presents with a history of fever and disseminated skin lesions.
      Polymerase chain reaction testing of skin biopsy specimens should be performed
      more systematically if the results of routine microbiological investigations
      remain unrevealing. In addition, silver staining of skin lesions can help
      establish the diagnosis. Eventually, testing for immune deficiencies should more
      routinely follow a confirmed diagnosis of chronic meningococcemia.

PMID- 24577071
TI  - Multiple hybridization events in Cardamine (Brassicaceae) during the last 150
      years: revisiting a textbook example of neoallopolyploidy.
AB  - BACKGROUND AND AIMS: Recently formed allopolyploid species represent excellent
      subjects for exploring early stages of polyploid evolution. The hexaploid
      Cardamine schulzii was regarded as one of the few nascent allopolyploid species
      formed within the past ~150 years that presumably arose by autopolyploidization
      of a triploid hybrid, C. * insueta; however, the most recent investigations have
      shown that it is a trigenomic hybrid. The aims of this study were to explore the
      efficiency of progenitor-specific microsatellite markers in detecting the hybrid
      origins and genome composition of these two allopolyploids, to estimate the
      frequency of polyploid formation events, and to outline their evolutionary
      potential for long-term persistence and speciation. METHODS: Flow-cytometric
      ploidy-level screening and genotyping by progenitor-specific microsatellite
      markers (20 microsatellite loci) were carried out on samples focused on
      hybridizing populations at Urnerboden, Switzerland, but also including
      comparative material of the parental species from other sites in the Alps and
      more distant areas. KEY RESULTS: It was confirmed that hybridization between the
      diploids C. amara and C. rivularis auct. gave rise to triploid C. * insueta, and
      it is inferred that this has occurred repeatedly. Evidence is provided that C.
      schulzii comprises three parental genomes and supports its origin from
      hybridization events between C. * insueta and the locally co-occurring
      hypotetraploid C. pratensis, leading to two cytotypes of C. schulzii:
      hypopentaploid and hypohexaploid. Each cytotype of C. schulzii is genetically
      uniform, suggesting their single origins. CONCLUSIONS: Persistence of C. schulzii
      has presumably been achieved only by perennial growth and clonal reproduction.
      This contrasts with C. * insueta, in which multiple origins and occasional sexual
      reproduction have generated sufficient genetic variation for long-term survival
      and evolutionary success. This study illustrates a complex case of recurrent
      hybridization and polyploidization events, and highlights the role of triploids
      that promoted the origin of trigenomic hybrids.

PMID- 24577073
TI  - Caries process on occlusal surfaces: evolving evidence and understanding.
AB  - Management of the caries process on occlusal surfaces of permanent molars has
      proven a major challenge. The onset of caries on these surfaces takes place soon
      after their eruption, and the permanent first molars, followed by the second
      molars, remain the sites in the dentition which show the highest caries
      prevalence. This paper is structured in the form of questions and answers in
      which traditional concepts of caries susceptibility of occlusal surfaces are
      appraised and confronted with the current evidence. Then, research studies
      examining the role of biological determinants on the development and arrest of
      occlusal caries in young permanent teeth are discussed. Finally, the contribution
      of these studies in terms of developing the available scientific evidence and our
      understanding of the caries process on occlusal surfaces is analyzed. The current
      evidence does not support the concept that the early onset and high prevalence of
      occlusal caries in young permanent teeth are due to a particularly low inherent
      resistance of the occlusal surface or due to the presence of inaccessible fissure
      like structures on these surfaces. Evidence is provided to show that the most
      influential biological determinants of the development and arrest of occlusal
      caries are thick plaque accumulation on the groove-fossa system and the stage of
      tooth eruption limiting mechanical oral function. Consequently, active occlusal
      lesions are significantly more prevalent in erupting than in fully erupted teeth.
      The major contribution of this review is to provide updated knowledge about the
      biological principles determining the development and arrest of caries on
      occlusal surfaces of erupting teeth.

PMID- 24577074
TI  - Persistent spin excitations in doped antiferromagnets revealed by resonant
      inelastic light scattering.
AB  - How coherent quasiparticles emerge by doping quantum antiferromagnets is a key
      question in correlated electron systems, whose resolution is needed to elucidate
      the phase diagram of copper oxides. Recent resonant inelastic X-ray scattering
      (RIXS) experiments in hole-doped cuprates have purported to measure high-energy
      collective spin excitations that persist well into the overdoped regime and bear
      a striking resemblance to those found in the parent compound, challenging the
      perception that spin excitations should weaken with doping and have a diminishing
      effect on superconductivity. Here we show that RIXS at the Cu L3-edge indeed
      provides access to the spin dynamical structure factor once one considers the
      full influence of light polarization. Further we demonstrate that high-energy
      spin excitations do not correlate with the doping dependence of Tc, while low
      energy excitations depend sensitively on doping and show ferromagnetic
      correlations. This suggests that high-energy spin excitations are marginal to
      pairing in cuprate superconductors. 

PMID- 24577075
TI  - Decorative power generating panels creating angle insensitive transmissive
      colors.
AB  - We present ultra-thin (6 to 31 nm) undoped amorphous silicon/organic hybrid solar
      cell structure, which can transmit desired color of light. The transmitted colors
      show great angular tolerance due to the negligible optical phase associated with
      light propagating in ultra-thin amorphous silicon (a-Si) layers. We achieved the
      power conversion efficiency of the hybrid cells up to 2 %; and demonstrated that
      most of the absorbed photons in the undoped a-Si layer contributed to the
      extracted electric charges due to the suppressed electron-hole recombination in
      the ultra-thin a-Si layer. We also show the resonance is invariant with respect
      to the angle of incidence up to +/- 70 degrees  regardless of the polarization of
      the incident light. Our exploration provides a design to realize energy
      harvesting colored photovoltaic panels for innovative applications.

PMID- 24577078
TI  - Design, synthesis and photophysical studies of dipyrromethene-based materials:
      insights into their applications in organic photovoltaic devices.
AB  - This review article presents the most recent developments in the use of materials
      based on dipyrromethene (DPM) and azadipyrromethenes (ADPM) for organic
      photovoltaic (OPV) applications. These chromophores and their corresponding BF2
      chelated derivatives BODIPY and aza-BODIPY, respectively, are well known for
      fluorescence-based applications but are relatively new in the field of
      photovoltaic research. This review examines the variety of relevant designs,
      synthetic methodologies and photophysical studies related to materials that
      incorporate these porphyrinoid-related dyes in their architecture. The main idea
      is to inspire readers to explore new avenues in the design of next generation
      small-molecule and bulk-heterojunction solar cell (BHJSC) OPV materials based on
      DPM chromophores. The main concepts are briefly explained, along with the main
      challenges that are to be resolved in order to take full advantage of solar
      energy. 

PMID- 24577076
TI  - Prevalence of coronary artery fistulae after cardiac surgery. Comparison between
      coronary artery bypass grafting, valve surgery, and orthotopic heart
      transplantation.
AB  - INTRODUCTION: Coronary artery fistulae (CAF) are anomalous connections from a
      coronary artery to a recipient pulmonary vessel or cardiac chamber, and are
      reported in 0.2 % of the general population. The prevalence of CAF in the modern
      orthotopic heart transplant (OHT) population has been demonstrated to be
      significantly higher. The mechanism is unknown but one proposal is endothelial
      and vascular growth factor activation from injury. We hypothesize an incremental
      increase in CAF prevalence with the complexity of surgery, such that patients who
      have undergone OHT surgery would have an increased prevalence of CAF, as compared
      with patients who have undergone coronary artery bypass (CABG) surgery with valve
      surgery and as compared with patients who have undergone CABG surgery only.
      PATIENTS AND METHODS: Consecutive angiograms of 481 patients after CABG surgery
      and 432 patients after OHT were reviewed. Patients who had previous valve surgery
      in addition to CABG were identified. Presence of CAF was determined. The chi
      squared test was used for statistical analysis. RESULTS: In all, 436 patients had
      CABG only (group A), 45 patients had CABG with valve surgery (group B), and 432
      patients had OHT (group C). The mean age of patients at the time of surgery for
      group A, B, and C was 59.0, 66.1, and 55.3 years, respectively. The percentage of
      male patients was 78.4, 77.8, and 77.1 %, respectively. We found 10 patients (2.3
      %) with CAF in group A compared with 4 patients (8.9 %) in group B, and 88
      patients (20.4 %) in group C, which was statistically significant (p < 0.001).
      All CAF were small, were not associated with hemodynamic compromise or
      significant adverse events, and were managed conservatively. CONCLUSION: There is
      an increased prevalence of CAF formation both after CABG and OHT compared with
      the general population. The higher prevalence of CAF in patients who additionally
      underwent valve surgery or who underwent OHT may be attributed to differences in
      surgical complexity. The increased prevalence of CAF formation after OHT compared
      with CABG should be further investigated.

PMID- 24577079
TI  - Does strategy training reduce age-related deficits in working memory?
AB  - BACKGROUND: Older adults typically perform worse on measures of working memory
      (WM) than do young adults; however, age-related differences in WM performance
      might be reduced if older adults use effective encoding strategies. OBJECTIVE:
      The purpose of the current experiment was to evaluate WM performance after
      training individuals to use effective encoding strategies. METHODS: Participants
      in the training group (older adults: n = 39; young adults: n = 41) were taught
      about various verbal encoding strategies and their differential effectiveness and
      were trained to use interactive imagery and sentence generation on a list
      learning task. Participants in the control group (older: n = 37; young: n = 38)
      completed an equally engaging filler task. All participants completed a pre- and
      post-training reading span task, which included self-reported strategy use, as
      well as two transfer tasks that differed in the affordance to use the trained
      strategies - a paired-associate recall task and the self-ordered pointing task.
      RESULTS: Both young and older adults were able to use the target strategies on
      the WM task and showed gains in WM performance after training. The age-related WM
      deficit was not greatly affected, however, and the training gains did not
      transfer to the other cognitive tasks. In fact, participants attempted to adapt
      the trained strategies for a paired-associate recall task, but the increased
      strategy use did not benefit their performance. CONCLUSIONS: Strategy training
      can boost WM performance, and its benefits appear to arise from strategy-specific
      effects and not from domain-general gains in cognitive ability.

PMID- 24577080
TI  - DJ-1 protects against cell death following acute cardiac ischemia-reperfusion
      injury.
AB  - Novel therapeutic targets are required to protect the heart against cell death
      from acute ischemia-reperfusion injury (IRI). Mutations in the DJ-1 (PARK7) gene
      in dopaminergic neurons induce mitochondrial dysfunction and a genetic form of
      Parkinson's disease. Genetic ablation of DJ-1 renders the brain more susceptible
      to cell death following ischemia-reperfusion in a model of stroke. Although DJ-1
      is present in the heart, its role there is currently unclear. We sought to
      investigate whether mitochondrial DJ-1 may protect the heart against cell death
      from acute IRI by preventing mitochondrial dysfunction. Overexpression of DJ-1 in
      HL-1 cardiac cells conferred the following beneficial effects: reduced cell death
      following simulated IRI (30.4+/-4.7% with DJ-1 versus 52.9+/-4.7% in control;
      n=5, P<0.05); delayed mitochondrial permeability transition pore (MPTP) opening
      (a critical mediator of cell death) (260+/-33 s with DJ-1 versus 121+/-12 s in
      control; n=6, P<0.05); and induction of mitochondrial elongation (81.3+/-2.5%
      with DJ-1 versus 62.0+/-2.8% in control; n=6 cells, P<0.05). These beneficial
      effects of DJ-1 were absent in cells expressing the non-functional DJ-1(L166P)
      and DJ-1(Cys106A) mutants. Adult mice devoid of DJ-1 (KO) were found to be more
      susceptible to cell death from in vivo IRI with larger myocardial infarct sizes
      (50.9+/-3.5% DJ-1 KO versus 41.1+/-2.5% in DJ-1 WT; n>=7, P<0.05) and resistant
      to cardioprotection by ischemic preconditioning. DJ-1 KO hearts showed increased
      mitochondrial fragmentation on electron microscopy, although there were no
      differences in calcium-induced MPTP opening, mitochondrial respiratory function
      or myocardial ATP levels. We demonstrate that loss of DJ-1 protects the heart
      from acute IRI cell death by preventing mitochondrial dysfunction. We propose
      that DJ-1 may represent a novel therapeutic target for cardioprotection. 

PMID- 24577081
TI  - High-dose of vitamin C supplementation reduces amyloid plaque burden and
      ameliorates pathological changes in the brain of 5XFAD mice.
AB  - Blood-brain barrier (BBB) breakdown and mitochondrial dysfunction have been
      implicated in the pathogenesis of Alzheimer's disease (AD), a neurodegenerative
      disease characterized by cognitive deficits and neuronal loss. Besides vitamin C
      being as one of the important antioxidants, recently, it has also been reported
      as a modulator of BBB integrity and mitochondria morphology. Plasma levels of
      vitamin C are decreased in AD patients, which can affect disease progression.
      However, investigation using animal models on the role of vitamin C in the AD
      pathogenesis has been hampered because rodents produce with no dependence on
      external supply. Therefore, to identify the pathogenic importance of vitamin C in
      an AD mouse model, we cross-bred 5 familial Alzheimer's disease mutation (5XFAD)
      mice (AD mouse model) with iota-gulono-gamma-lactone oxidase (Gulo) knockout (KO)
      mice, which are unable to synthesize their own vitamin C, and produced Gulo KO
      mice with 5XFAD mice background (KO-Tg). These mice were maintained on either low
      (0.66 g/l) or high (3.3 g/l) supplementation of vitamin C. We found that the
      higher supplementation of vitamin C had reduced amyloid plaque burden in the
      cortex and hippocampus in KO-Tg mice, resulting in amelioration of BBB disruption
      and mitochondrial alteration. These results suggest that intake of a larger
      amount of vitamin C could be protective against AD-like pathologies. 

PMID- 24577082
TI  - Akt and mTOR mediate programmed necrosis in neurons.
AB  - Necroptosis is a newly described form of regulated necrosis that contributes to
      neuronal death in experimental models of stroke and brain trauma. Although much
      work has been done elucidating initiating mechanisms, signaling events governing
      necroptosis remain largely unexplored. Akt is known to inhibit apoptotic neuronal
      cell death. Mechanistic target of rapamycin (mTOR) is a downstream effector of
      Akt that controls protein synthesis. We previously reported that dual inhibition
      of Akt and mTOR reduced acute cell death and improved long term cognitive
      deficits after controlled-cortical impact in mice. These findings raised the
      possibility that Akt/mTOR might regulate necroptosis. To test this hypothesis, we
      induced necroptosis in the hippocampal neuronal cell line HT22 using concomitant
      treatment with tumor necrosis factor alpha (TNFalpha) and the pan-caspase
      inhibitor N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone. TNFalpha/zVAD
      treatment induced cell death within 4 h. Cell death was preceded by RIPK1-RIPK3
      pAkt assembly, and phosphorylation of Thr-308 and Thr473 of AKT and its direct
      substrate glycogen synthase kinase-3beta, as well as mTOR and its direct
      substrate S6 ribosomal protein (S6), suggesting activation of Akt/mTOR pathways.
      Pretreatment with Akt inhibitor viii and rapamycin inhibited Akt and S6
      phosphorylation events, mitochondrial reactive oxygen species production, and
      necroptosis by over 50% without affecting RIPK1-RIPK3 complex assembly. These
      data were confirmed using small inhibitory ribonucleic acid-mediated knockdown of
      AKT1/2 and mTOR. All of the aforementioned biochemical events were inhibited by
      necrostatin-1, including Akt and mTOR phosphorylation, generation of oxidative
      stress, and RIPK1-RIPK3-pAkt complex assembly. The data suggest a novel,
      heretofore unexpected role for Akt and mTOR downstream of RIPK1 activation in
      neuronal cell death. 

PMID- 24577083
TI  - The LEF1/CYLD axis and cIAPs regulate RIP1 deubiquitination and trigger apoptosis
      in selenite-treated colorectal cancer cells.
AB  - Inhibitor-of-apoptosis protein (IAP) inhibitors have been reported to
      synergistically reduce cell viability in combination with a variety of
      chemotherapeutic drugs via targeted cellular IAP (cIAP) depletion. Here, we found
      that cIAP silencing sensitised colorectal cancer (CRC) cells to selenite-induced
      apoptosis. Upon selenite treatment, the K63-linked ubiquitin chains on receptor
      interacting protein 1 (RIP1) were removed, leading to the formation of the death
      inducing complex and subsequent caspase-8 activation. Although the ubiquitinases
      cIAP1 and cIAP2 were significantly downregulated after a 24-h selenite treatment,
      cylindromatosis (CYLD) deubiquitinase protein levels were marginally upregulated.
      Chromatin immunoprecipitation assays revealed that lymphoid enhancer factor-1
      (LEF1) dissociated from the CYLD promoter upon selenite treatment, thus
      abolishing suppression of CYLD gene expression. We corroborated these findings in
      a CRC xenograft animal model using immunohistochemistry. Collectively, our
      findings demonstrate that selenite caused CYLD upregulation via LEF1 and cIAP
      downregulation, both of which contribute to the degradation of ubiquitin chains
      on RIP1 and subsequent caspase-8 activation and apoptosis. Importantly, our
      results identify a LEF1-binding site in the CYLD promoter as a potential target
      for combinational therapy as an alternative to cIAPs. 

PMID- 24577084
TI  - Necroptosis induced by RIPK3 requires MLKL but not Drp1.
AB  - Necroptosis is a mechanism by which cells can kill themselves that does not
      require caspase activity or the presence of the pro-apoptotic Bcl-2 family
      members Bax or Bak. It has been reported that RIPK3 (receptor interacting protein
      kinase 3) activates MLKL (mixed lineage kinase domain-like) to cause cell death
      that requires dynamin-related protein 1 (Drp1), because survival was increased in
      cells depleted of Drp1 or treated with the Drp1 inhibitor mdivi-1. To analyze
      necroptosis in a system that does not require addition of tumor necrosis factor
      (TNF), we used a construct that allows RIPK3 to be induced in cells, and then
      dimerized via an E. coli gyrase domain fused to its carboxyl-terminus, using the
      dimeric gyrase binding antibiotic coumermycin. We have previously shown elsewhere
      that RIPK3 dimerized in this manner not only induces necroptosis but also
      apoptosis, which can be inhibited by the broad-spectrum caspase inhibitor Q-VD
      OPh (QVD). In response to RIPK3 dimerization, wild-type mouse embryonic
      fibroblasts (MEFs) underwent cell death that was reduced but not completely
      blocked by QVD. In contrast, death upon dimerization of RIPK3 in Mlkl(-/-) MEFs
      was completely inhibited with QVD, confirming that MLKL is required for
      necroptosis. Similar to wild-type MEFs, most Drp1(-/-) MEFs died when RIPK3 was
      activated, even in the presence of QVD. Furthermore, overexpression of wild-type
      MLKL or dominant active mutants of MLKL (Q343A or S345E/S347E) caused death of
      wild-type and Drp1(-/-) MEFs that was not inhibited with QVD. These results
      indicate that necroptosis caused by RIPK3 requires MLKL but not Drp1. 

PMID- 24577085
TI  - Inducement of mitosis delay by cucurbitacin E, a novel tetracyclic triterpene
      from climbing stem of Cucumis melo L., through GADD45gamma in human brain
      malignant glioma (GBM) 8401 cells.
AB  - Cucurbitacin E (CuE) is a natural compound previously shown to have anti-feedant,
      antioxidant and antitumor activities as well as a potent chemo-preventive action
      against cancer. The present study investigates its anti-proliferative property
      using MTT assay; CuE demonstrated cytotoxic activity against malignant glioma GBM
      8401 cells and induced cell cycle G2/M arrest in these cells. CuE-treated cells
      accumulated in metaphase (CuE 2.5-10 MUM) as determined using MPM-2 by flow
      cytometry. We attempted to characterize the molecular pathways responsible for
      cytotoxic effects of CuE in GBM 8401 cells. We studied the genome-wide gene
      expression profile on microarrays and molecular networks by using pathway
      analysis tools of bioinformatics. The CuE reduced the expression of 558 genes and
      elevated the levels of 1354 genes, suggesting an existence of the common pathways
      involved in induction of G2/M arrest. We identified the RB (GADD45beta and
      GADD45gamma) and the p53 (GADD45alpha) signaling pathways as the common pathways,
      serving as key molecules that regulate cell cycle. Results indicate that CuE
      produced G2/M arrest as well as the upregulation of GADD45 gamma and binding with
      CDC2. Both effects increased proportionally with the dose of CuE, suggesting that
      the CuE-induced mitosis delay is regulated by GADD45gamma overexpression. Our
      findings suggest that, in addition to the known effects on cancer prevention, CuE
      may have antitumor activity in glioma therapy. 

PMID- 24577086
TI  - Metformin promotes autophagy and apoptosis in esophageal squamous cell carcinoma
      by downregulating Stat3 signaling.
AB  - The antidiabetic drug metformin exerts chemopreventive and antineoplastic effects
      in many types of malignancies. However, the mechanisms responsible for metformin
      actions appear diverse and may differ in different types of cancer. Understanding
      the molecular and cellular mechanisms specific for different cancers is important
      to optimize strategy for metformin treatment in different cancer types. Here, we
      investigate the in vitro and in vivo effects of metformin on esophageal squamous
      cell carcinoma (ESCC) cells. Metformin selectively inhibited cell growth in ESCC
      tumor cells but not immortalized noncancerous esophageal epithelial cells. In
      addition to apoptosis, metformin triggered autophagy. Pharmacological or genetic
      inhibition of autophagy sensitized ESCC cells to metformin-induced apoptotic cell
      death. Mechanistically, signal transducer and activator of transcription 3
      (Stat3) and its downstream target Bcl-2 was inactivated by metformin treatment.
      Accordingly, small interfering RNA (siRNA)-mediated Stat3 knockdown enhanced
      metformin-induced autophagy and apoptosis, and concomitantly enhanced the
      inhibitory effect of metformin on cell viability. Similarly, the Bcl-2 proto
      oncogene, an inhibitor of both apoptosis and autophagy, was repressed by
      metformin. Ectopic expression of Bcl-2 protected cells from metformin-mediated
      autophagy and apoptosis. In vivo, metformin downregulated Stat3 activity and Bcl
      2 expression, induced apoptosis and autophagy, and inhibited tumor growth.
      Together, inactivation of Stat3-Bcl-2 pathway contributes to metformin-induced
      growth inhibition of ESCC by facilitating crosstalk between apoptosis and
      autophagy. 

PMID- 24577088
TI  - MiRNA-210 modulates a nickel-induced cellular energy metabolism shift by
      repressing the iron-sulfur cluster assembly proteins ISCU1/2 in Neuro-2a cells.
AB  - The cellular energy metabolism shift, characterized by the inhibition of
      oxidative phosphorylation (OXPHOS) and enhancement of glycolysis, is involved in
      nickel-induced neurotoxicity. MicroRNA-210 (miR-210) is regulated by hypoxia
      inducible transcription factor-1alpha (HIF-1alpha) under hypoxic conditions and
      controls mitochondrial energy metabolism by repressing the iron-sulfur cluster
      assembly protein (ISCU1/2). ISCU1/2 facilitates the assembly of iron-sulfur
      clusters (ISCs), the prosthetic groups that are critical for mitochondrial
      oxidation-reduction reactions. This study aimed to investigate whether miR-210
      modulates alterations in energy metabolism after nickel exposure through
      suppressing ISCU1/2 and inactivating ISCs-containing metabolic enzymes. We
      determined that NiCl2 exposure leads to a significant accumulation of HIF-1alpha,
      rather than HIF-1beta, in Neuro-2a cells. The miR-210 overexpression and ISCU1/2
      downregulation was observed in a dose- and time-dependent manner. The gain-of
      function and loss-of-dysfunction assays revealed that miR-210 mediated the
      ISCU1/2 suppression, energy metabolism alterations, and ISC-containing metabolic
      enzyme inactivation after nickel exposure. In addition, the impact of miR-210 on
      ISC-containing metabolic enzymes was independent from cellular iron regulation.
      Overall, these data suggest that repression of miR-210 on ISCU1/2 may contribute
      to HIF-1alpha-triggered alterations in energy metabolism after nickel exposure. A
      better understanding of how nickel impacts cellular energy metabolism may
      facilitate the elucidation of the mechanisms by which nickel affects the human
      health. 

PMID- 24577087
TI  - Glucose metabolism and hexosamine pathway regulate oncogene-induced senescence.
AB  - Oncogenic stress-induced senescence (OIS) prevents the ability of oncogenic
      signals to induce tumorigenesis. It is now largely admitted that the mitogenic
      effect of oncogenes requires metabolic adaptations to respond to new energetic
      and bio constituent needs. Yet, whether glucose metabolism affects OIS response
      is largely unknown. This is largely because of the fact that most of the OIS
      cellular models are cultivated in glucose excess. In this study, we used human
      epithelial cells, cultivated without glucose excess, to study alteration and
      functional role of glucose metabolism during OIS. We report a slowdown of glucose
      uptake and metabolism during OIS. Increasing glucose metabolism by expressing
      hexokinase2 (HK2), which converts glucose to glucose-6-phosphate (G6P), favors
      escape from OIS. Inversely, expressing a glucose-6-phosphatase, [corrected]
      pharmacological inhibition of HK2, or adding nonmetabolizable glucose induced a
      premature senescence. Manipulations of various metabolites covering G6P
      downstream pathways (hexosamine, glycolysis, and pentose phosphate pathways)
      suggest an unexpected role of the hexosamine pathway in controlling OIS.
      Altogether, our results show that decreased glucose metabolism occurs during and
      participates to OIS.

PMID- 24577089
TI  - Impact of human papilloma virus infection on the response of head and neck
      cancers to anti-epidermal growth factor receptor antibody therapy.
AB  - Infection with human papillomaviruses (HPVs) characterizes a distinct subset of
      head and neck squamous cell cancers (HNSCCs). HPV-positive HNSCC preferentially
      affect the oropharynx and tonsils. Localized HPV-positive HNSCCs have a favorable
      prognosis and treatment outcome. However, the impact of HPV in advanced or
      metastatic HNSCC remains to be defined. In particular, it is unclear whether HPV
      modulates the response to cetuximab, an antibody targeting the epidermal growth
      factor receptor (EGFR), which is a mainstay of treatment of advanced HNSCC. To
      this end, we have examined the sensitivity of HPV-positive and -negative HNSCC
      models to cetuximab and cytotoxic drugs in vitro and in vivo. In addition, we
      have stably expressed the HPV oncogenes E6 and E7 in cetuximab-sensitive cancer
      cell lines to specifically investigate their role in the antibody response. The
      endogenous HPV status or the expression of HPV oncogenes had no significant
      impact on cetuximab-mediated suppression of EGFR signaling and proliferation in
      vitro. Cetuximab effectively inhibited the growth of E6- and E7-expressing tumors
      grafted in NOD/SCID mice. In support, formalin-fixed, paraffin-embedded tumor
      samples from cetuximab-treated patients with recurrent or metastatic HNSCC were
      probed for p16(INK4a) expression, an established biomarker of HPV infection.
      Response rates (45.5% versus 45.5%) and median progression-free survival (97
      versus 92 days) following cetuximab-based therapy were similar in patients with
      p16(INK4A)-positive and p16(INK4A)-negative tumors. In conclusion, HPV oncogenes
      do not modulate the anti-EGFR antibody response in HSNCC. Cetuximab treatment
      should be administered independently of HPV status. 

PMID- 24577090
TI  - Knockdown of BAG3 induces epithelial-mesenchymal transition in thyroid cancer
      cells through ZEB1 activation.
AB  - The process by which epithelial features are lost in favor of a mesenchymal
      phenotype is referred to as epithelial-mesenchymal transition (EMT). Most
      carcinomas use this mechanism to evade into neighboring tissues. Reduction or a
      loss of E-cadherin expression is a well-established hallmark of EMT. As a potent
      suppressor of E-cadherin, transcription factor ZEB1 is one of the key inducers of
      EMT, whose expression promotes tumorigenesis and metastasis of carcinomas. Bcl-2
      associated athanogene 3 (BAG3) affects multifaceted cellular functions, including
      proliferation, apoptosis, cell adhesion and invasion, viral infection, and
      autophagy. Recently, we have reported a novel role of BAG3 implicated in EMT,
      while the mechanisms are poorly elucidated. The current study demonstrated that
      knockdown of BAG3 induced EMT, and increased cell migratory and invasiveness in
      thyroid cancer cells via transcriptional activation of ZEB1. We also found that
      BAG3 knockdown led to nuclear accumulation of beta-catenin, which was responsible
      for the transcriptional activation of ZEB1. These results indicate BAG3 as a
      regulator of ZEB1 expression in EMT and as a regulator of metastasis in thyroid
      cancer cells, providing potential targets to prevent and/or treat thyroid cancer
      cell invasion and metastasis. 

PMID- 24577091
TI  - An unexpected role for a Wnt-inhibitor: Dickkopf-1 triggers a novel cancer
      survival mechanism through modulation of aldehyde-dehydrogenase-1 activity.
AB  - It is widely accepted that canonical Wnt (cWnt) signaling is required for the
      differentiation of osteoprogenitors into osteoblasts. Furthermore, tumor-derived
      secretion of the cWnt-antagonist Dickkopf-1 (Dkk-1) is known to cause bone
      destruction, inhibition of repair and metastasis in many bone malignancies, but
      its role in osteosarcoma (OS) is still under debate. In this study, we examined
      the role of Dkk-1in OS by engineering its overexpression in the osteochondral
      sarcoma line MOS-J. Consistent with the known role of Dkk-1 in osteoblast
      differentiation, Dkk-1 inhibited osteogenesis by the MOSJ cells themselves and
      also in surrounding tissue when implanted in vivo. Surprisingly, Dkk-1 also had
      unexpected effects on MOSJ cells in that it increased proliferation and
      resistance to metabolic stress in vitro and caused the formation of larger and
      more destructive tumors than controls upon orthotopic implantation. These effects
      were attributed in part to upregulation of the stress response enzyme and cancer
      stem cell marker aldehyde-dehydrogenase-1 (ALDH1). Direct inhibition of ALDH1
      reduced viability under stressful culture conditions, whereas pharmacological
      inhibition of cWnt or overexpression of ALDH1 had a protective effect.
      Furthermore, we observed that ALDH1 was transcriptionally activated in a c-Jun
      dependent manner through a pathway consisting of RhoA, MAP-kinase-kinase-4 and
      Jun N-terminal Kinase (JNK), indicating that noncanonical planar cell polarity
      like Wnt signaling was the mechanism responsible. Together, our results therefore
      demonstrate that Dkk-1 enhances resistance of OS cells to stress by tipping the
      balance of Wnt signaling in favor of the non-canonical Jun-mediated Wnt pathways.
      In turn, this results in transcriptional activation of ALDH1 through Jun
      responsive promoter elements. This is the first report linking Dkk-1 to tumor
      stress resistance, further supporting the targeting of Dkk-1 not only to prevent
      and treat osteolytic bone lesions but also to reduce numbers of stress-resistant
      tumor cells. 

PMID- 24577092
TI  - Glycogen synthase kinase 3beta represses MYOGENIN function in alveolar
      rhabdomyosarcoma.
AB  - MYOGENIN is a member of the muscle regulatory factor family that orchestrates an
      obligatory step in myogenesis, the terminal differentiation of skeletal muscle
      cells. A paradoxical feature of alveolar rhabdomyosarcoma (ARMS), a prevalent
      soft tissue sarcoma in children arising from cells with a myogenic phenotype, is
      the inability of these cells to undergo terminal differentiation despite the
      expression of MYOGENIN. The chimeric PAX3-FOXO1 fusion protein which results from
      a chromosomal translocation in ARMS has been implicated in blocking cell cycle
      arrest, preventing myogenesis from occurring. We report here that PAX3-FOXO1
      enhances glycogen synthase kinase 3beta (GSK3beta) activity which in turn
      represses MYOGENIN activity. MYOGENIN is a GSK3beta substrate in vitro on the
      basis of in vitro kinase assays and MYOGENIN is phosphorylated in ARMS-derived
      RH30 cells. Constitutively active GSK3beta(S9A) increased the level of a
      phosphorylated form of MYOGENIN on the basis of western blot analysis and this
      effect was reversed by neutralization of the single consensus GSK3beta
      phosphoacceptor site by mutation (S160/164A). Congruently, GSK3beta inhibited the
      trans-activation of an E-box reporter gene by wild-type MYOGENIN, but not
      MYOGENIN with the S160/164A mutations. Functionally, GSK3beta repressed muscle
      creatine kinase (MCK) promoter activity, an effect which was reversed by the
      S160/164A mutated MYOGENIN. Importantly, GSK3beta inhibition or exogenous
      expression of the S160/164A mutated MYOGENIN in ARMS reduced the anchorage
      independent growth of RH30 cells in colony-formation assays. Thus, sustained
      GSK3beta activity represses a critical regulatory step in the myogenic cascade,
      contributing to the undifferentiated, proliferative phenotype in alveolar
      rhabdomyosarcoma (ARMS). 

PMID- 24577096
TI  - Compositional disorder and its effect on the thermoelectric performance of Zn3P2
      nanowire-copper nanoparticle composites.
AB  - Recent studies indicated that nanowire format of materials is ideal for enhancing
      the thermoelectric performance of materials. Most of these studies were performed
      using individual nanowires as the test elements. It is not currently clear
      whether bulk assemblies of nanowires replicate this enhanced thermoelectric
      performance of individual nanowires. Therefore, it is imperative to understand
      whether enhanced thermoelectric performance exhibited by individual nanowires can
      be extended to bulk assemblies of nanowires. It is also imperative to know
      whether the addition of metal nanoparticle to semiconductor nanowires can be
      employed for enhancing their thermoelectric performance further. Specifically, it
      is important to understand the effect of microstructure and composition on the
      thermoelectric performance on bulk compound semiconductor nanowire-metal
      nanoparticle composites. In this study, bulk composites composed of mixtures of
      copper nanoparticles with either unfunctionalized or 1,4-benzenedithiol (BDT)
      functionalized Zn3P2 nanowires were fabricated and analyzed for their
      thermoelectric performance. The results indicated that use of BDT functionalized
      nanowires for the fabrication of composites leads to interface-engineered
      composites that have uniform composition all across their cross-section. The
      interface engineering allows for increasing their Seebeck coefficients and
      electrical conductivities, relative to the Zn3P2 nanowire pellets. In contrast,
      the use of unfunctionalized Zn3P2 nanowires for the fabrication of composite
      leads to the formation of composites that are non-uniform in composition across
      their cross-section. Ultimately, the composites were found to have Zn3P2
      nanowires interspersed with metal alloy nanoparticles. Such non-uniform
      composites exhibited very high electrical conductivities, but slightly lower
      Seebeck coefficients, relative to Zn3P2 nanowire pellets. These composites were
      found to show a very high zT of 0.23 at 770 K, orders of magnitude higher than
      either interface-engineered composites or Zn3P2 nanowire pellets. The results
      indicate that microstructural composition of semiconductor nanowire-metal
      nanoparticle composites plays a major role in determining their thermoelectric
      performance, and such composites exhibit enhanced thermoelectric performance.

PMID- 24577095
TI  - Complications of intrathecal baclofen pumps in children: experience from a
      tertiary care center.
AB  - BACKGROUND/AIMS: Intrathecal baclofen (ITB) therapy is useful in treating
      spasticity and dystonia but it has many complications, more so in children. The
      main aim of the study was to look at the complications of ITB pumps in children
      with the goal of future prevention. METHODS: Charts of all patients <=21 years
      with an ITB pump, implanted by a single pediatric neurosurgeon, at a single
      center, between 1996 and 2011 were reviewed retrospectively. Data regarding an
      ITB test trial were also recorded. RESULTS: During 1996-2011, 119 children (mean
      age 13.2 years) underwent ITB pump placement; 84% had spastic quadriplegic
      cerebral palsy. The gross motor function classification system level was >=4 for
      most. The pump was removed in 5 (4.2%) patients due to inefficacy. The mean
      follow-up was 38 months. Mechanical complications requiring pump and/or catheter
      revision occurred in 19.3% and infections in an additional 21.8%. Seven patients
      (6%) had meningitis. No complication was noted after 72 months of initial pump
      insertion, even after pump reinsertion. CONCLUSION: There is a need for better
      infection control as well as better pump, catheter and surgical technology to
      lower the complications of ITB pumps in children.

PMID- 24577093
TI  - MicroRNA-21 regulates T-cell apoptosis by directly targeting the tumor suppressor
      gene Tipe2.
AB  - MicroRNAs (MiRs) are short noncoding RNAs that can regulate gene expression. It
      has been reported that miR-21 suppresses apoptosis in activated T cells, but the
      molecular mechanism remains undefined. Tumor suppressor Tipe2 (or tumor necrosis
      factor-alpha-induced protein 8 (TNFAIP8)-like 2 (TNFAIP8L2)) is a newly
      identified anti-inflammatory protein of the TNFAIP8 family that is essential for
      maintaining immune homeostasis. We report here that miR-21 is a direct target of
      nuclear factor-kappaB and could regulate Tipe2 expression in a Tipe2 coding
      region-dependent manner. In activated T cells and macrophages, Tipe2 expression
      was markedly downregulated, whereas miR-21 expression was upregulated.
      Importantly, Tipe2-deficient T cells were significantly less sensitive to
      apoptosis. Conversely, overexpression of Tipe2 in EL-4 T cells increased their
      susceptibility to activation-induced apoptosis. Therefore, Tipe2 provides a
      molecular bridge between miR-21 and cell apoptosis; miR-21 suppresses apoptosis
      in activated T cells at least in part through directly targeting tumor suppressor
      gene Tipe2. 

PMID- 24577094
TI  - PTEN regulates AMPA receptor-mediated cell viability in iPS-derived motor
      neurons.
AB  - Excitatory transmission in the brain is commonly mediated by the alpha-amino-3
      hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors. In amyotrophic
      lateral sclerosis (ALS), AMPA receptors allow cytotoxic levels of calcium into
      neurons, contributing to motor neuron injury. We have previously shown that
      oculomotor neurons resistant to the disease process in ALS show reduced AMPA
      mediated inward calcium currents compared with vulnerable spinal motor neurons.
      We have also shown that PTEN (phosphatase and tensin homolog deleted on
      chromosome 10) knockdown via siRNA promotes motor neuron survival in models of
      spinal muscular atrophy (SMA) and ALS. It has been reported that inhibition of
      PTEN attenuates the death of hippocampal neurons post injury by decreasing the
      effective translocation of the GluR2 subunit into the membrane. In addition,
      leptin can regulate AMPA receptor trafficking via PTEN inhibition. Thus, we
      speculate that manipulation of AMPA receptors by PTEN may represent a potential
      therapeutic strategy for neuroprotective intervention in ALS and other
      neurodegenerative disorders. To this end, the first step is to establish a
      fibroblast-iPS-motor neuron in vitro cell model to study AMPA receptor
      manipulation. Here we report that iPS-derived motor neurons from human
      fibroblasts express AMPA receptors. PTEN depletion decreases AMPA receptor
      expression and AMPA-mediated whole-cell currents, resulting in inhibition of AMPA
      induced neuronal death in primary cultured and iPS-derived motor neurons. Taken
      together, our results imply that PTEN depletion may protect motor neurons by
      inhibition of excitatory transmission that represents a therapeutic strategy of
      potential benefit for the amelioration of excitotoxicity in ALS and other
      neurodegenerative disorders. 

PMID- 24577097
TI  - Phosphatidylserine containing omega-3 Fatty acids may improve memory abilities in
      nondemented elderly individuals with memory complaints: results from an open
      label extension study.
AB  - BACKGROUND: The present study is an open-label extension (OLE) aimed at
      evaluating the effect of 100 mg/day of phosphatidylserine enriched with
      docosahexaenoic acid (PS-DHA) on cognitive performance in nondemented elderly
      individuals with memory complaints. METHODS: From the participants who completed
      the core study, 122 continued with a 15-week OLE. Efficacy was assessed using a
      computerized tool and the Clinical Global Impression of Change (CGI-C) rating
      scale. RESULTS: A significant improvement in sustained attention and memory
      recognition was observed in the PS-DHA naive group, while the PS-DHA continuers
      maintained their cognitive status. Additionally, a significant improvement in CGI
      C was observed in the naive group. CONCLUSIONS: The results demonstrate that
      consumption of 100 mg/day of PS-DHA might be associated with improving or
      maintaining cognitive status in elderly subjects with memory complaints.

PMID- 24577099
TI  - Feasibility and safety of outpatient medical thoracoscopy at a large tertiary
      medical center: a collaborative medical-surgical initiative.
AB  - BACKGROUND: Medical thoracoscopy (MT) is performed by relatively few
      pulmonologists in the United States. Recognizing that an outpatient minimally
      invasive procedure such as MT could provide a suitable alternative to
      hospitalization and surgery in patients with undiagnosed exudative pleural
      effusions, we initiated the Mayo Clinic outpatient MT program and herein report
      preliminary data on safety, feasibility, and outcomes. METHODS: All consecutive
      patients referred for outpatient MT from October 2011 to August 2013 were
      included in this study. Demographic, radiographic, procedural, and histologic
      data were recorded prospectively and subsequently analyzed. RESULTS: Outpatient
      MT was performed on 51 patients, with the most common indication being an
      undiagnosed lymphocytic exudative effusion in 86.3% of the cohort. Endoscopic
      findings included diffuse parietal pleural inflammation in 26 patients (51%),
      parietal pleural studding in 19 patients (37.3%), a normal examination in three
      patients (5.9%), diffuse parietal pleural thickening in two patients (3.9%), and
      a diaphragmatic defect in one patient (2%). Pleural malignancy was the most
      common histologic diagnosis in 24 patients (47.1%) and composed predominantly of
      mesothelioma in 14 (27.5%). Nonspecific pleuritis was the second most frequent
      diagnosis in 23 patients (45.1%). There were very few complications, with no
      significant cases of hemodynamic or respiratory compromise and no deaths.
      CONCLUSIONS: Outpatient MT can be integrated successfully into a busy tertiary
      referral medical center through the combined efforts of interventional
      pulmonologists and thoracic surgeons. Outpatient MT may provide patients with a
      more convenient alternative to an inpatient surgical approach in the diagnosis of
      undiagnosed exudative pleural effusions while maintaining a high diagnostic yield
      and excellent safety.

PMID- 24577098
TI  - FGF7/KGF regulates autophagy in keratinocytes: A novel dual role in the induction
      of both assembly and turnover of autophagosomes.
AB  - Autophagy is a degradative pathway through which cells overcome stressful
      conditions and rapidly change their phenotype during differentiation. Despite its
      protective role, when exacerbated, autophagy may lead to cell death. Several
      growth factors involved in cell survival and in preventing differentiation are
      able to inhibit autophagy. Here we investigated the autophagic role of FGF7/KGF,
      an important player in epithelial cell protection and differentiation.
      Biochemical and quantitative fluorescence approaches showed that FGF7 and its
      signaling induce autophagy in human keratinocytes and the use of specific
      inhibitors indicated that this effect is independent of the PI3K-AKT-MTOR
      pathway. The selective block of autophagosome-to-lysosome fusion clarified that
      FGF7 induces autophagy stimulating autophagosome formation. However, quantitative
      fluorescence approaches also indicated that, upon a prolonged autophagic
      stimulus, FGF7 is able to accelerate autophagosome turnover. Moreover, in
      differentiating keratinocytes, the use of the autophagic inhibitor 3-MA as well
      as the depletion of BECN1 and ATG5, 2 essential regulators of the process,
      counteracted the FGF7-induced increase of the differentiation marker KRT1/K1,
      suggesting that autophagy is required for the FGF7-mediated early
      differentiation. These results provide the first evidence of a role of FGF7 in
      the regulation of sequential steps of the autophagic process and strengthen the
      hypothesis of a direct interplay between autophagy and differentiation. On the
      other hand, the ability of FGF7 to accelerate autophagosome turnover, preventing
      their dangerous accumulation, is consistent with the well-established protective
      role played by the growth factor in epithelial cells.

PMID- 24577101
TI  - The HEXACO Honesty-Humility, Agreeableness, and Emotionality factors: a review of
      research and theory.
AB  - We review research and theory on the HEXACO personality dimensions of Honesty
      Humility (H), Agreeableness (A), and Emotionality (E), with particular attention
      to the following topics: (1) the origins of the HEXACO model in lexical studies
      of personality structure, and the content of the H, A, and E factors in those
      studies; (2) the operationalization of the H, A, and E factors in the HEXACO
      Personality Inventory-Revised; (3) the construct validity of self-reports on
      scales measuring the H factor; (4) the theoretical distinction between H and A;
      (5) similarity and assumed similarity between social partners in personality,
      with a focus on H and A; (6) the extent to which H (and A and E) variance is
      represented in instruments assessing the "Five-Factor Model" of personality; and
      (7) the relative validity of scales assessing the HEXACO and Five-Factor Model
      dimensions in predicting criteria conceptually relevant to H, A, and E. 

PMID- 24577102
TI  - Hormonal signaling in the gut.
AB  - The gut is anatomically positioned to play a critical role in the regulation of
      metabolic homeostasis, providing negative feedback via nutrient sensing and local
      hormonal signaling. Gut hormones, such as cholecystokinin (CCK) and glucagon-like
      peptide-1 (GLP-1), are released following a meal and act on local receptors to
      regulate glycemia via a neuronal gut-brain axis. Additionally, jejunal nutrient
      sensing and leptin action are demonstrated to suppress glucose production, and
      both are required for the rapid antidiabetic effect of duodenal jejunal bypass
      surgery. Strategies aimed at targeting local gut hormonal signaling pathways may
      prove to be efficacious therapeutic options to improve glucose control in
      diabetes. 

PMID- 24577103
TI  - Identification of fibroblast growth factor-18 as a molecule to protect adult
      articular cartilage by gene expression profiling.
AB  - To identify genes that maintain the homeostasis of adult articular cartilage and
      regenerate its lesions, we initially compared four types of chondrocytes:
      articular (AA) versus growth plate (AG) cartilage chondrocytes in adult rats, and
      superficial layer (IS) versus deep layer (ID) chondrocytes of epiphyseal
      cartilage in infant rats. Microarray analyses revealed that 40 and 186 genes had
      >=10-fold higher expression ratios of AA/AG and IS/ID, respectively, and 16 genes
      showed >=10-fold of both AA/AG and IS/ID ratios. The results were validated by
      real-time RT-PCR analysis. Among them, Hoxd1, Fgf18, and Esm1 were expressed more
      strongly in AA than in IS. Fgf18 was the extracellular and secreted factor that
      decreased glycosaminoglycan release and depletion from the cartilage, and
      enhanced proliferation of articular chondrocytes. Fgf18 was strongly expressed in
      the articular cartilage chondrocytes of adult rats. In a surgical rat
      osteoarthritis model, a once-weekly injection of recombinant human FGF18
      (rhFGF18) given 3 weeks after surgery prevented cartilage degeneration in a dose
      dependent manner at 6 and 9 weeks after surgery, with significant effect at 10
      MUg/week of rhFGF18. As the underlying mechanism, rhFGF18 strongly up-regulated
      Timp1 expression in the cell and organ cultures, and inhibition of aggrecan
      release by rhFGF18 was restored by addition of an antibody to Timp1. In
      conclusion, we have identified Fgf18 as a molecule that protects articular
      cartilage by gene expression profiling, and the anticatabolic effects may at
      least partially be mediated by the Timp1 expression. 

PMID- 24577107
TI  - Tailoring nanostructures in micrometer size germanium particles to improve their
      performance as an anode for lithium ion batteries.
AB  - A facile and scalable single-step approach is employed to synthesize a bulk
      germanium electrode, which consists of nanoscale Ge-grains in ~5 MUm porous
      powders. This three-dimensional Ge electrode exhibits superior specific capacity
      (~1500 mA h g(-1)) and cyclic performance, attributed to its unique
      lithiation/delithiation processes. 

PMID- 24577105
TI  - Three-dimensional visualization of nanostructured surfaces and bacterial
      attachment using Autodesk(r) Maya(r).
AB  - There has been a growing interest in understanding the ways in which bacteria
      interact with nano-structured surfaces. As a result, there is a need for
      innovative approaches to enable researchers to visualize the biological processes
      taking place, despite the fact that it is not possible to directly observe these
      processes. We present a novel approach for the three-dimensional visualization of
      bacterial interactions with nano-structured surfaces using the software package
      Autodesk Maya. Our approach comprises a semi-automated stage, where actual
      surface topographic parameters, obtained using an atomic force microscope, are
      imported into Maya via a custom Python script, followed by a 'creative stage',
      where the bacterial cells and their interactions with the surfaces are visualized
      using available experimental data. The 'Dynamics' and 'nDynamics' capabilities of
      the Maya software allowed the construction and visualization of plausible
      interaction scenarios. This capability provides a practical aid to knowledge
      discovery, assists in the dissemination of research results, and provides an
      opportunity for an improved public understanding. We validated our approach by
      graphically depicting the interactions between the two bacteria being used for
      modeling purposes, Staphylococcus aureus and Pseudomonas aeruginosa, with
      different titanium substrate surfaces that are routinely used in the production
      of biomedical devices. 

PMID- 24577104
TI  - Differential affinity of FLIP and procaspase 8 for FADD's DED binding surfaces
      regulates DISC assembly.
AB  - Death receptor activation triggers recruitment of FADD, which via its death
      effector domain (DED) engages the DEDs of procaspase 8 and its inhibitor FLIP to
      form death-inducing signalling complexes (DISCs). The DEDs of FADD, FLIP and
      procaspase 8 interact with one another using two binding surfaces defined by
      alpha1/alpha4 and alpha2/alpha5 helices, respectively. Here we report that FLIP
      has preferential affinity for the alpha1/alpha4 surface of FADD, whereas
      procaspase 8 has preferential affinity for FADD's alpha2/alpha5 surface. These
      relative affinities contribute to FLIP being recruited to the DISC at comparable
      levels to procaspase 8 despite lower cellular expression. Additional studies,
      including assessment of DISC stoichiometry and functional assays, suggest that
      following death receptor recruitment, the FADD DED preferentially engages FLIP
      using its alpha1/alpha4 surface and procaspase 8 using its alpha2/alpha5 surface;
      these tripartite intermediates then interact via the alpha1/alpha4 surface of
      FLIP DED1 and the alpha2/alpha5 surface of procaspase 8 DED2. 

PMID- 24577108
TI  - Brain activation associated with pride and shame.
AB  - BACKGROUND: Self-referential emotions such as shame/guilt and pride provide
      evaluative information about persons themselves. In addition to emotional
      aspects, social and self-referential processes play a role in self-referential
      emotions. Prior studies have rather focused on comparing self-referential and
      other-referential processes of one valence, triggered mostly by external stimuli.
      In the current study, we aimed at investigating the valence-specific neural
      correlates of shame/guilt and pride, evoked by the remembrance of a corresponding
      autobiographical event during functional magnetic resonance imaging. METHOD: A
      total of 25 healthy volunteers were studied. The task comprised a negative
      (shame/guilt), a positive (pride) and a neutral condition (expecting the
      distractor). Each condition was initiated by a simple cue, followed by the
      remembrance and finished by a distracting picture. RESULTS: Pride and shame/guilt
      conditions both activated typical emotion-processing circuits including the
      amygdala, insula and ventral striatum, as well as self-referential brain regions
      such as the bilateral dorsomedial prefrontal cortex. Comparing the two emotional
      conditions, emotion-processing circuits were more activated by pride than by
      shame, possibly due to either hedonic experiences or stronger involvement of the
      participants in positive self-referential emotions due to a self-positivity bias.
      However, the ventral striatum was similarly activated by pride and shame/guilt.
      In the whole-brain analysis, both self-referential emotion conditions activated
      medial prefrontal and posterior cingulate regions, corresponding to the self
      referential aspect and the autobiographical evocation of the respective emotions.
      CONCLUSION: Autobiographically evoked self-referential emotions activated basic
      emotional as well as self-referential circuits. Except for the ventral striatum,
      emotional circuits were more active with pride than with shame.

PMID- 24577109
TI  - Synthesis, characterization, oxygen electrocatalysis and OFET properties of novel
      mono- and ball-type metallophthalocyanines.
AB  - Novel mono- and ball-type Co(ii), Zn(ii) and Cu(ii) metallophthalocyanines (MPcs)
      were synthesized from 1,1'-p-anisylidenbis(2-naphthoxyphthalonitrile). The MPcs
      have been characterized by elemental analysis, UV/Vis, IR and (1)H-NMR
      spectroscopy and MALDI-TOF mass spectrometry. The performances of organic field
      effect transistors (OFETs) of the dinuclear ball-type MPcs have been compared to
      those of mononuclear counterparts. The ball-type MPc based OFETs showed a p
      channel and typical ambipolar transport properties. On the other hand, it was not
      possible to measure the full transfer characteristics of the mononuclear MPc
      based devices. The best results were obtained in the case of dinuclear Cu2Pc2. In
      this case, the mobility value is MU = 4.4 * 10(-2) cm(2) V(-1) s(-1) and the
      threshold voltage is 27.6 volts. The reduction and oxidation characteristics of
      the mono-nuclear and ball-type MPcs have been compared by cyclic voltammetry,
      square wave voltammetry and controlled potential coulometry on platinum in
      nonaqueous media. The comparison suggested that the ball-type complexes form ring
      based and/or metal-based mixed-valence species as a result of the remarkable
      interaction between the two Pc rings and/or metal centers. The stability of these
      species was confirmed by the mixed-valence splitting values for the complexes.
      The electrocatalytic performances of the mononuclear and dinuclear complexes for
      the oxygen reduction reaction were also studied. The compounds involving Co(ii)
      at the phthalocyanine core, especially the ball-type one, showed much higher
      catalytic performances towards oxygen reduction than those of the other ones. 

PMID- 24577110
TI  - Fully automated closed-loop ventilation is safe and effective in post-cardiac
      surgery patients.

PMID- 24577111
TI  - Spindle cell squamous carcinoma during BRAF inhibitor therapy for advanced
      melanoma: an aggressive secondary neoplasm of undetermined biologic potential.

PMID- 24577113
TI  - The superiority of silver nanoellipsoids synthesized via a new approach in
      suppressing the coffee-ring effect during drying and film formation processes.
AB  - Silver nanoellipsoids (Ag NEs) with about 40 nm diameter minor axis and 100 nm
      major axis were prepared by a typical polyol process in the presence of
      poly(vinyl pyrrolidone), using Cl(-) as etching agent at the early stage of
      synthesis and poly(ethylene glycol) at the later stage to control the size. A
      suspension of these kinds of Ag NEs can resist the coffee-ring effect and deposit
      uniform films after drying. By contrast, suspensions of spherical silver
      nanoparticles suffer the coffee-ring effect badly, always leaving a ring on the
      edge of patterns after evaporation is complete. The reasons behind these
      phenomena can be mainly attributed to the long-ranged interparticle attraction
      between Ag NEs that preserves them from being transported by Marangoni flows
      during the drying process. These Ag NEs will be very useful in the preparation of
      conductive inks. They can perform well in the solidification process of printed
      patterns, forming uniform and smooth films, greatly enhancing the printing
      efficiency.

PMID- 24577112
TI  - Adrenal enzyme impairment in neonates and adolescents treated with ritonavir and
      protease inhibitors for HIV exposure or infection.
AB  - BACKGROUND: Human deficiency virus (HIV) protease inhibitors (PIs) are widely
      used drugs whose effects are pharmacologically enhanced by ritonavir, a potent
      cytochrome P450 inhibitor. We reported previously that prophylactic postnatal
      ritonavir-PI therapy in HIV-exposed neonates was associated with increases in
      plasma 17-hydroxyprogesterone (17-OHP) and dehydroepiandrosterone sulfate (DHEA
      S). AIMS: To further investigate adrenal function in neonates and adolescents
      given ritonavir-PI. METHODS: Adrenal function was assessed prospectively in 3 HIV
      exposed neonates given short-term prophylactic treatment and 3 HIV-infected
      adolescents given long-term treatment. Plasma cortisol, 17-OHP, 17-OH
      pregnenolone, DHEA-S, and androstenedione were measured before and after ACTH
      administration. RESULTS: None of the patients had clinical signs of adrenal
      dysfunction. The only neonate exposed to ritonavir-PI in utero had up to 3-fold
      increases in plasma 17-OHP. Increases in 17-OH-pregnenolone of up to 3.1-fold
      were noted in 4 of the 6 patients, and all 6 patients had elevations in DHEA-S
      (up to 20.4-fold increase) and/or DHEA (up to 4.7-fold) and/or androstenedione
      (up to 5.2-fold). All these parameters improved after treatment completion.
      CONCLUSION: Neonates and adolescents given ritonavir-PI exhibit a similar adrenal
      dysfunction profile consistent with an impact on multiple adrenal enzymes. These
      abnormalities require evaluation, given the potentially long exposure times.

PMID- 24577114
TI  - Phosphorylation of eIF2alpha is dispensable for differentiation but required at a
      posttranscriptional level for paneth cell function and intestinal homeostasis in
      mice.
AB  - BACKGROUND: Recent studies link endoplasmic reticulum (ER) stress and the
      unfolded protein response (UPR) to inflammatory bowel disease. Altered eIF2alpha
      phosphorylation (eIF2alpha-P), a regulatory hub of the UPR, was observed in
      mucosal tissue of patients with inflammatory bowel disease. In this study, we
      examined the mechanistic role of eIF2alpha-P in intestinal epithelial cell (IEC)
      function and intestinal homeostasis in mice. METHODS: We generated mice with
      villin-Cre-mediated conditional expression of nonphosphorylatable Ser51Ala mutant
      eIF2alpha in IECs (AA mice). We analyzed AA mice under normal conditions and on
      challenge with oral infection of Salmonella Typhimurium or dextran sulfate sodium
      induced colitis. RESULTS: Loss of eIF2alpha-P did not affect the normal
      proliferation or differentiation of IECs. However, AA mice expressed decreased
      secretory proteins including lysozyme, suggesting eIF2alpha-P is required for
      Paneth cell function. The ultrastructure of AA Paneth cells exhibited a reduced
      number of secretory granules, a fragmented ER, and distended mitochondria under
      normal conditions. UPR gene expression was defective in AA IECs. Translation of
      Paneth cell specific messenger RNAs encoding lysozyme and cryptidins was
      significantly defective leading to the observed granule-deficient phenotype,
      which was associated with reduced ribosomal recruitment of these messenger RNAs
      to the ER membrane. Consequently, AA mice were more susceptible to oral
      Salmonella infection and dextran sulfate sodium-induced colitis. CONCLUSIONS: We
      conclude eIF2alpha phosphorylation is required for the normal function of
      intestinal Paneth cells and mucosal homeostasis by activating UPR signaling and
      promoting messenger RNA recruitment to the ER membrane for translation.

PMID- 24577116
TI  - Mini-laparoscopy is superior in detecting liver cirrhosis and metastases in liver
      cancer: an over 10-year experience in 1,788 cases.
AB  - BACKGROUND/AIMS: Mini-laparoscopy has, since its first description in 1998,
      proven to be a valuable diagnostic method in liver diseases. We re-evaluated the
      significance of mini-laparoscopy for diagnosis and staging of liver disease and
      primary liver and bile duct cancer. PATIENTS AND METHODS: 1,788 consecutive
      patients who received a diagnostic mini-laparoscopy between 10/1998 and 06/2011
      were included in this retrospective cohort study. RESULTS: In chronic liver
      disease, cirrhosis was detected by mini-laparoscopy in 27% of cases. A comparison
      of microscopic versus macroscopic diagnosis of cirrhosis revealed a sampling
      error for histology alone of 21%. Macroscopic inspection of the liver surface
      contributed to the diagnosis of unknown liver diseases in approximately 38%. In
      patients with bile duct or liver cancer, mini-laparoscopy led to upstaging of the
      disease in 33 and 23%, respectively. Major complications (bowel perforation and
      delayed bleeding) occurred in 0.39% of cases. CONCLUSIONS: Mini-laparoscopy is a
      valuable procedure with significant diagnostic impact in known and unknown
      inflammatory and malignant liver diseases. It can be safely performed even in
      patients with acute liver failure and severe coagulopathy and the diagnostic
      value does not differ from diagnostic laparoscopy performed with standard
      instruments.

PMID- 24577118
TI  - Simulation of coherence selection by pulsed field gradients in liquid-state NMR
      using an auxiliary matrix formalism.
AB  - An algorithm for simulating coherence selection due to a pulse sequence element
      consisting of two pulsed field gradients separated by a short collection of
      pulses and delays is introduced. This algorithm involves computation of the
      matrix exponential of an auxiliary matrix twice the size of the system
      Liouvillian, a dimensional increase smaller than is required with other known
      computational methods. Approximations valid for most simulations of liquid-state
      NMR spectra are involved in the derivation. Diffusion is omitted, but could be
      treated in an approximate way as a damping over the pulse sequence element.
      Several NMR pulse sequences using gradients for coherence selection have been
      implemented, making use of the functionality of Spinach
      (http://spindynamics.org/Spinach.php). Example simulations testing these
      implementations are presented, and the extent to which the formal dimensional
      reduction can lead to a speedup in simulation time discussed. It is found that
      the previously known methods can be made competitive with the auxiliary matrix
      method by making use of their embarrassingly parallel nature. Cases where the
      relative dimensional reduction of the auxiliary matrix method is very large, or
      where efficient parallelization of the simulation independent of the nature of
      the algorithm used exists, are found to lead to situations beneficial for the
      auxiliary matrix algorithm in this comparison. 

PMID- 24577117
TI  - Impact of tumor HPV status on outcome in patients with recurrent and/or
      metastatic squamous cell carcinoma of the head and neck receiving chemotherapy
      with or without cetuximab: retrospective analysis of the phase III EXTREME trial.
AB  - BACKGROUND: Tumor human papillomavirus (HPV) status is an important prognostic
      factor in locoregionally advanced squamous cell carcinoma of the head and neck
      (SCCHN). Prognostic value in recurrent and/or metastatic (R/M) disease remains to
      be confirmed. This retrospective analysis of the EXTREME trial, comparing
      chemotherapy plus cetuximab with chemotherapy first line in R/M SCCHN,
      investigated efficacy and prognosis according to tumor p16 and HPV status.
      PATIENTS AND METHODS: Paired tissue samples were used: p16INK4A expression was
      assessed by immunohistochemistry, and HPV status determined in extracted DNA
      samples using oligonucleotide hybridization assays. RESULTS: Altogether, 416 of
      442 patients had tumor samples available for p16 and HPV: 10% of tumors were p16
      positive and 5% were HPV positive. Adding cetuximab to chemotherapy improved
      survival, irrespective of tumor p16 or HPV status. This pattern remained in a
      combined analysis of p16 and HPV. p16 positivity and HPV positivity were
      associated with prolonged survival compared with p16 negativity and HPV
      negativity. Subgroup analysis of patients with oropharyngeal cancer demonstrated
      a similar pattern to all evaluable patients. CONCLUSION: The results from this
      analysis suggest that p16 and HPV status have prognostic value in R/M SCCHN and
      survival benefits of chemotherapy plus cetuximab over chemotherapy alone are
      independent of tumor p16 and HPV status.

PMID- 24577115
TI  - Could a swimming creature inform us on intestinal diseases? Lessons from
      zebrafish.
AB  - Understanding a complex pathology such as inflammatory bowel disease, where host
      genetics (innate and adaptive immunity, barrier function) and environmental
      factors (microbes, diet, and stress) interact together to influence disease onset
      and severity, requires multipronged approaches to model these numerous variables.
      Researchers have typically relied on preclinical models of mouse and rat origin
      to push the boundary of knowledge further. However, incorporation of novel
      vertebrate models may contribute to new knowledge on specific aspects of
      intestinal homeostasis. An emerging literature has seen the use of zebrafish as a
      novel animal system to study key aspects of host-microbe interactions in the
      intestine. In this review, we briefly introduce components of host-microbiota
      interplay in the developing zebrafish intestine and summarize key lessons learned
      from this animal system; review important chemically induced and genetically
      engineered zebrafish models of intestinal immune disorders; and discuss
      perspectives and limitations of the zebrafish model system.

PMID- 24577119
TI  - Gonadal asymmetry and sex determination in birds.
AB  - Although vertebrates display a superficial bilateral symmetry, most internal
      organs develop and locate with a consistent left:right asymmetry. There is still
      considerable debate as to when this process actually begins, but it seems that,
      at least for some species, the initial steps occur at a very early stage of
      development. In recent years, a number of model systems, including the chick
      embryo, have been utilised to increase our understanding of the molecular basis
      of this complex developmental process. While the basic elements of asymmetry are
      clearly conserved in chick development, the chick embryo also exhibits an
      additional unusual asymmetry in terms of the development of the gonads. In the
      female chick embryo, only 1 gonad and accessory structures fully develop, with
      the result that the adult hen has only 1 ovary and a single oviduct - both on the
      left side. With a small number of exceptions, this is a consistent feature of
      avian development. Here, we describe the morphological development and molecular
      basis of this unusual asymmetry, consider the implications for avian sex
      determination, and discuss the possible biological reasons why many birds have
      adopted a single-ovary system.

PMID- 24577120
TI  - Follistatin in chondrocytes: the link between TRPV4 channelopathies and skeletal
      malformations.
AB  - Point mutations in the calcium-permeable TRPV4 ion channel have been identified
      as the cause of autosomal-dominant human motor neuropathies, arthropathies, and
      skeletal malformations of varying severity. The objective of this study was to
      determine the mechanism by which TRPV4 channelopathy mutations cause skeletal
      dysplasia. The human TRPV4(V620I) channelopathy mutation was transfected into
      primary porcine chondrocytes and caused significant (2.6-fold) up-regulation of
      follistatin (FST) expression levels. Pore altering mutations that prevent calcium
      influx through the channel prevented significant FST up-regulation (1.1-fold). We
      generated a mouse model of the TRPV4(V620I) mutation, and found significant
      skeletal deformities (e.g., shortening of tibiae and digits, similar to the human
      disease brachyolmia) and increases in Fst/TRPV4 mRNA levels (2.8-fold). FST was
      significantly up-regulated in primary chondrocytes transfected with 3 different
      dysplasia-causing TRPV4 mutations (2- to 2.3-fold), but was not affected by an
      arthropathy mutation (1.1-fold). Furthermore, FST-loaded microbeads decreased
      bone ossification in developing chick femora (6%) and tibiae (11%). FST gene and
      protein levels were also increased 4-fold in human chondrocytes from an
      individual natively expressing the TRPV4(T89I) mutation. Taken together, these
      data strongly support that up-regulation of FST in chondrocytes by skeletal
      dysplasia-inducing TRPV4 mutations contributes to disease pathogenesis.

PMID- 24577123
TI  - Association of 2 neurotrophic factor polymorphisms with efficacy of paroxetine in
      patients with major depressive disorder in a Chinese population.
AB  - BACKGROUND: To evaluate the influence of the single nucleotide polymorphism (SNP)
      rs 6265 in the brain-derived neurotrophic factor (BDNF) gene and 21 SNPs of the
      glial cell line-derived neurotrophic factor (GDNF) gene on the efficacy of
      paroxetine in patients with major depressive disorder (MDD). METHODS: Genotyping
      for BDNF and GDNF polymorphisms was performed in 298 patients with MDD who
      started 20 mg paroxetine per day and had their plasma concentrations measured
      after 6 weeks. The SNPs were selected from the HapMap Chinese ethnic group and
      literature reports. Changes in the severity of MDD were assessed with the
      Hamilton Depression Rating Scale (HAM-D) at baseline and at a 6-week follow-up.
      Paroxetine plasma concentration was measured using high-performance liquid
      chromatography with fluorescence detection. The Sequenom MassArray system was
      used for genotyping. RESULTS: At the 6-week follow-up, 219 of the 298 patients
      (73.5%) were responders and 79 patients (26.5%) were nonresponders to paroxetine
      treatment. The lower threshold concentration of paroxetine for response was 50
      ng/mL, and a linear relationship was found between paroxetine plasma
      concentration and clinical response. The allele types for the SNPs rs 6265 (P <
      0.001), rs 2973049 (P = 0.005), and rs 2216711 (P = 0.006) demonstrated
      significant associations with paroxetine treatment remission at week 6.
      CONCLUSIONS: Genetic variants in the BDNF and GDNF regions may be indicators of
      treatment response to paroxetine in patients with MDD.

PMID- 24577122
TI  - Sensitivity and specificity of EtG in hair as a marker of chronic excessive
      drinking: pooled analysis of raw data and meta-analysis of diagnostic accuracy
      studies.
AB  - BACKGROUND: To assess the debated diagnostic performance of ethyl glucuronide in
      the 3-cm proximal scalp hair fraction (HEtG) as a marker of chronic excessive
      drinking. METHODS: In July 2012/May 2013, after a systematic search through the
      MEDLINE, OVID/EMBASE, WEB OF SCIENCE, and SCOPUS databases, 8 studies were
      included in the pooled analysis that report raw single data on HEtG concentration
      and self-reported daily alcohol intake (SDAI). A receiver operating
      characteristic curve analysis and a Spearman rank-order correlation test were
      used. A meta-analysis was performed following the Preferred Reporting Items for
      Systematic Reviews and Meta-Analyses and Cochrane recommendations, comprising
      quality and bias assessments. RESULTS: The pooled analysis showed that 30 pg/mg
      could be a useful cutoff value for HEtG to detect an SDAI >60 g/d and
      demonstrated a parabolic direct correlation between HEtG and SDAI data [rho 0.79;
      95% confidence interval (CI), 0.69-0.87; P < 0.001]. The meta-analysis found an
      overall HEtG sensitivity of 0.96 (95% CI, 0.72-1.00) and a specificity of 0.99
      (95% CI, 0.92-1.00); a nomogram to predict the posttest probability of exhibiting
      the targeted condition in the general population was built. Significant
      variability among the included studies was detected, which was mainly explained
      by true heterogeneity in the presence of publication bias. CONCLUSIONS: With the
      available data, we conclude that HEtG is a promising marker for identifying
      chronic excessive drinking. Nonetheless, larger and well-designed population
      studies are required to draw any definitive conclusions on the significance and
      appropriateness of its application in the forensic setting.

PMID- 24577121
TI  - A human sleep homeostasis phenotype in mice expressing a primate-specific PER3
      variable-number tandem-repeat coding-region polymorphism.
AB  - In humans, a primate-specific variable-number tandem-repeat (VNTR) polymorphism
      (4 or 5 repeats 54 nt in length) in the circadian gene PER3 is associated with
      differences in sleep timing and homeostatic responses to sleep loss. We
      investigated the effects of this polymorphism on circadian rhythmicity and sleep
      homeostasis by introducing the polymorphism into mice and assessing circadian and
      sleep parameters at baseline and during and after 12 h of sleep deprivation (SD).
      Microarray analysis was used to measure hypothalamic and cortical gene
      expression. Circadian behavior and sleep were normal at baseline. The response to
      SD of 2 electrophysiological markers of sleep homeostasis, electroencephalography
      (EEG) theta power during wakefulness and delta power during sleep, were greater
      in the Per3(5/5) mice. During recovery, the Per3(5/5) mice fully compensated for
      the SD-induced deficit in delta power, but the Per3(4/4) and wild-type mice did
      not. Sleep homeostasis-related transcripts (e.g., Homer1, Ptgs2, and Kcna2) were
      differentially expressed between the humanized mice, but circadian clock genes
      were not. These data are in accordance with the hypothesis derived from human
      data that the PER3 VNTR polymorphism modifies the sleep homeostatic response
      without significantly influencing circadian parameters.

PMID- 24577124
TI  - Point-of-care coagulation testing for assessment of the pharmacodynamic
      anticoagulant effect of direct oral anticoagulant.
AB  - BACKGROUND: This investigation was carried out with already available point-of
      care testing (POCT) systems for coagulation parameters to evaluate the
      qualitative and semiquantitative determination of the time- and concentration
      dependent anticoagulant effects of the direct oral anticoagulants rivaroxaban and
      dabigatran. METHODS: The whole blood prothrombin time (PT), activated partial
      thromboplastin time (aPTT), and activated clotting time (ACT) were determined
      using the GEM PCL Plus coagulation system. Whole blood PT was also measured on
      the CoaguCheck XS instrument. In addition, PT and aPTT values were obtained in
      citrated plasma using the PT reagent Neoplastin Plus and the STA APTT reagent.
      Drug concentrations of rivaroxaban and dabigatran were determined with a
      chromogenic anti-Xa assay and the hemoclot assay, which are reported to have good
      agreement with liquid chromatography coupled with tandem mass spectrometry
      measurements. POCT was performed in 27 consecutive patients who received
      rivaroxaban 10, 15, or 20 mg once daily and in 15 patients receiving dabigatran
      110 or 150 mg twice daily. Blood samples were collected predose and 2 hours after
      observed drug intake at steady state. RESULTS: Two hours after observed
      rivaroxaban administration, the whole blood PT measured on the GEM PCL Plus was
      prolonged by an average of 64.5% in comparison with predose levels. Less
      differentiation was observed for rivaroxaban when the PT was measured on the
      CoaguCheck XS instrument or in plasma (prolongation of 24.1% and 36.8%,
      respectively). After 2 hours observed dabigatran administration, the whole blood
      aPTT was comparable with plasma values and was prolonged by 23.5% in comparison
      with trough values. Significant concentration-dependent prolongations of the
      activated clotting time were observed to different extents for both direct
      anticoagulants. CONCLUSIONS: Direct oral anticoagulants display variable ex vivo
      effects on different POCT-assays. POCT for aPTT is sensitive to increased
      concentrations of dabigatran, whereas the PT-POCT assessed with test systems such
      as the GEM PCL Plus may be helpful to measure the pharmacodynamic anticoagulant
      effects of rivaroxaban in emergency clinical situations.

PMID- 24577125
TI  - Therapeutic drug monitoring of levetiracetam: comparison of a novel immunoassay
      with an HPLC method.
AB  - BACKGROUND: Therapeutic drug monitoring of the anticonvulsant levetiracetam may
      be indicated in patients with conditions that may alter pharmacokinetic
      characteristics, for tailoring individual dosage regimens or to investigate
      patient compliance. In this study, the Bio-Rad high-performance liquid
      chromatography (HPLC) method (in-use method) and the ARK immunoassay method (new
      method) for levetiracetam monitoring in serum were compared. METHODS:
      Levetiracetam concentrations were determined in 63 samples using: (1)
      "Levetiracetam by HPLC" kit by Bio-Rad (Hercules, CA) on the Agilent 1100 HPLC
      system, and (2) "ARK Levetiracetam" immunoassay by ARK Diagnostics Inc (Fremont,
      CA) on the CDx90 platform by ThermoFisher Scientific Inc. RESULTS: Within
      laboratory imprecision and bias of the new method evaluated over a 20-day period
      were 7.4% and 0.5% at 7.5 mcg/mL, 4.5% and 1.9% at 30 mcg/mL, and 3.1% and 2.0%
      at 75 mcg/mL. Passing-Bablok regression analysis (X:Bio-Rad; Y:Ark) showed a
      nonsignificant intercept of 0.16 [95% confidence interval (CI), -0.55 to 0.72]
      and a slope marginally significantly different from unity of 0.95 (95% CI, 0.90
      0.99), which suggested minimum proportional systematic error. In agreement, Bland
      Altman analysis showed minimum systematic bias of 1.0 mcg/mL (95% CI, 0.32-1.69)
      with 95% of the HPLC-Ark differences ranging from -4.3 (95% CI, -5.52 to -3.16)
      to 6.3 (95% CI, 5.16-7.52). Our data showed that the 2 methods were identical
      both within inherent imprecision and analytical quality specifications (maximum
      allowable error 15%). CONCLUSIONS: The new Ark method on the CDx platform is
      acceptable and may be used to measure serum levetiracetam concentrations
      routinely.

PMID- 24577127
TI  - The influence of chloride impurities on Pt/C fuel cell catalyst corrosion.
AB  - Potentiodynamic Pt/C fuel cell catalyst corrosion has been studied as a function
      of chloride concentration with an electrochemical flow cell (EFC) coupled with
      highly sensitive ICP-MS. The Pt corrosion mechanism changes significantly: the
      anodic corrosion is much enhanced compared to the cathodic corrosion that
      prevails in electrolytes without Cl(-). 

PMID- 24577126
TI  - Trough concentration over 12.1 mg/L is a major risk factor of vancomycin-related
      nephrotoxicity in patients with therapeutic drug monitoring.
AB  - BACKGROUND: High doses of vancomycin increase the risk of nephrotoxicity, but the
      quantitative relationship between vancomycin exposure and nephrotoxicity is still
      controversial. This study evaluated the relationship between vancomycin trough
      concentration and nephrotoxicity, and risk factors for nephrotoxicity in patients
      undergoing therapeutic drug monitoring. METHODS: A total of 1269 cases from
      patients who underwent therapeutic drug monitoring were collected from 2006 to
      2010. Receiver operating characteristic curve analysis was used to evaluate the
      relationship between trough concentration and the incidence of nephrotoxicity.
      Logistic regression using the generalized Least Absolute Shrinkage and Selection
      Operator (lasso) method was used to evaluate possible risk factors for
      nephrotoxicity. The data were divided into high/low-concentration groups by the
      cutoff value obtained from the receiver operating characteristic curve, and
      additional logistic regression using the generalized lasso method was performed
      for each group. RESULTS: The cutoff value of the vancomycin trough concentration
      was 12.1 mg/L. Patients with high concentrations (>12.1 mg/L) were more likely to
      develop nephrotoxicity (odds ratio = 16.0, 95% confidence interval, 8.2-31.1).
      The vancomycin trough concentration was the only significant risk factor for
      nephrotoxicity identified using the generalized lasso (P < 0.001). In contrast,
      no factor was associated with nephrotoxicity in the low-concentration group.
      CONCLUSIONS: Vancomycin trough concentrations over 12.1 mg/L were associated with
      an increased risk of nephrotoxicity. This is lower than the known threshold.
      Trough vancomycin concentration over the threshold was the only risk factor of
      nephrotoxicity among demographic factors, dosing regimen, and other clinical
      conditions in this study. It is suggested that vancomycin trough concentrations
      greater than 12.1 mg/L require close monitoring for nephrotoxicity.

PMID- 24577128
TI  - Lower Ras expression as an independent predictor of patient outcomes in lung
      cancer treated with bevacizumab plus chemotherapy.
AB  - The objective of this study was to analyze the predictive roles of
      VEGF/KDR/Ras/MAPK gene expression in patients with advanced non-small-cell lung
      cancer (NSCLC) treated with bevacizumab plus chemotherapy. Twenty-five patients
      participating in an open-label phase IV trial (SAiL, MO19390) with available
      tumor tissues were analyzed. The mRNA expression levels of VEGF, kinase insert
      domain receptor (KDR), Ras, and mitogen-activated protein kinase (MAPK) in tumor
      tissues were detected using real-time quantitative PCR methods. The relationships
      between gene expression and disease control rate (DCR), progression-free survival
      (PFS), and overall survival (OS) were assessed. Patients with lower Ras
      expression had a longer PFS and OS than patients with higher expression (median
      PFS, 9.9 vs 5.5 months, chi(2)=3.944, P=0.047; OS, 19.3 vs 7.1 months,
      chi(2)=9.384, P=0.002). The PFS and OS of patients with lower and higher MAPK
      expression exhibited a marginal and significant difference (median PFS, 9.9 vs
      5.5 months, chi(2)=3.464, P=0.063; OS, 19.3 vs 9.7 months, chi(2)=5.298,
      P=0.021), respectively. Multivariate analyses using Cox's proportional hazards
      model showed that Ras is an independent predictor of OS (chi(2)=9.384, P=0.002).
      No differences in DCR were found according to Ras expression level. The results
      indicate that Ras is an independent predictor of OS. Thus, patients with lower
      Ras expression are most likely to benefit from bevacizumab plus chemotherapy
      treatment regimen. Patients with higher levels of Ras should receive other
      inhibitors that target Ras. The results also suggest that gene therapies that
      decrease RAS expression combined with bevacizumab may improve lung cancer
      treatment. Although there is a very important implication to patient selection in
      the target therapy, the data in this study are very preliminary owing to the too
      small sample size. Therefore, further research involving large numbers of
      patients and a prospective assessment of low and high RAS mRNA expressions
      getting the same treatments need to be done before conclusions can be made. 

PMID- 24577129
TI  - Silencing of FOXM1 transcription factor expression by adenovirus-mediated RNA
      interference inhibits human hepatocellular carcinoma growth.
AB  - The Forkhead Box M1 (FOXM1) transcription factor has been considered as a
      potential target for the prevention and/or therapeutic intervention in human
      carcinomas because of its roles in tumorigenesis and tumor progression through
      regulating the expression of genes relevant to cell proliferation and
      transformation. In this study, FOXM1 was found to express strongly in both
      clinical tissue specimens and human hepatocellular carcinoma (HCC) cell lines
      such as Huh-6, Huh-7 and HepG2. The knockdown of FOXM1 expression through an
      adenovirus vector (named AdFOXM1shRNA), which expresses a short hairpin RNA to
      downregulate FOXM1 expression specifically, diminished the proliferation of Huh-7
      and HepG2 cells and anchorage-independent growth of Huh-7 cells. Furthermore, we
      assessed the efficacy of AdFOXM1shRNA for tumor gene therapy with the Huh-7 cell
      xenograft mouse model and found that the tumor growth was significantly
      suppressed when inoculated mice were injected with AdFOXM1shRNA in the tumors.
      Together, our results suggest that FOXM1 is a potential therapeutic target for
      HCC and AdFOXM1shRNA may be an additional gene therapeutic intervention for HCC
      treatment. 

PMID- 24577130
TI  - Oncolytic virotherapy for osteosarcoma using midkine promoter-regulated
      adenoviruses.
AB  - Oncolytic virotherapy using adenoviruses has potential therapeutic benefits for a
      variety of cancers. We recently developed MOA5, a tumor-specific midkine promoter
      regulated oncolytic vector based on human adenovirus serotype 5 (Ad5). We
      modified the binding tropism of MOA5 by replacing the cell-binding domain of the
      Ad5 fiber knob with that from another adenovirus serotype 35 (Ad35); the
      resulting vector was designated MOA35. Here we evaluated the therapeutic
      efficacies of MOA5 and MOA35 for human osteosarcoma. Midkine mRNA expression and
      its promoter activity was significantly high in five human osteosarcoma cell
      lines, but was restricted in normal cells. Very low levels of adenovirus cellular
      receptor coxsackievirus/adenovirus receptor (CAR) (Ad5 receptor) expression were
      observed in MNNG-HOS and MG-63 cells, whereas high levels of CAR expression were
      seen in the other osteosarcoma cell lines. By contrast, CD46 (Ad35 receptor) was
      highly expressed in all osteosarcoma cell lines. Infectivity and in vitro
      cytocidal effect of MOA35 was significantly enhanced in MNNG-HOS and MG-63 cells
      compared with MOA5, although the cytocidal effects of MOA5 were sometimes higher
      in high CAR-expressing cell lines. In MG-63 xenograft models, MOA35 significantly
      enhanced antitumor effects compared with MOA5. Our findings indicate that MOA5
      and MOA35 allow tailored virotherapy and facilitate more effective treatments for
      osteosarcoma. 

PMID- 24577131
TI  - MHC-dependent inhibition of uterine NK cells impedes fetal growth and decidual
      vascular remodelling.
AB  - NK cells express variable receptors that engage polymorphic MHC class I molecules
      and regulate their function. Maternal NK cells accumulate at the maternal-fetal
      interface and can interact with MHC class I molecules from both parents. The
      relative contribution of the two sets of parental MHC molecules to uterine NK
      cell function is unknown. Here we show that, in mice, maternal and not paternal
      MHC educates uterine NK cells to mature and acquire functional competence. The
      presence of an additional MHC allele that binds more inhibitory than activating
      NK cell receptors results in suppressed NK cell function, compromised uterine
      arterial remodelling and reduced fetal growth. Notably, reduced fetal growth
      occurs irrespectively of the parental origin of the inhibitory MHC. This provides
      biological evidence for the impact of MHC-dependent NK inhibition as a risk
      factor for human pregnancy-related complications associated with impaired
      arterial remodelling. 

PMID- 24577132
TI  - Salvage radiotherapy in patients with prostate cancer and biochemical relapse
      after radical prostatectomy : Long-term follow-up of a single-center survey.
AB  - BACKGROUND AND PURPOSE: In patients with prostate cancer (PC) and biochemical
      relapse after radical prostatectomy, salvage radiotherapy (SRT) could improve PC
      specific survival (PCSS) but the timing for initiation is still under discussion.
      We have demonstrated a low rate of biochemical relapses in a patient series with
      very low pre-SRT PSA levels after a median follow-up of 42 months. Here, we
      present an update of that study. PATIENTS AND METHODS: Overall, 151 patients were
      analyzed. A biochemical relapse after SRT was diagnosed when the PSA exceeded the
      post-SRT nadir by 0.2 ng/ml with subsequent increase. Parameters with significant
      impact on biochemical progression-free survival (BPFS), PCSS, and overall
      survival (OS) in univariate analysis were included in a multiple Cox regression
      analysis. RESULTS: After a median follow-up of 82 months, 18 patients (12%) had
      died with 10 (6.6%) deaths being PC-related. A biochemical progression was
      diagnosed in 83 patients (55%). Univariate analysis revealed a significant impact
      of pre-SRT PSA level, Gleason score, and PSA doubling time (PSADT) on BPFS and
      for initial tumor stage and Gleason score on OS. Multivariate analysis confirmed
      the impact of pre-SRT PSA level, Gleason score, and PSADT on BPFS and tumor stage
      on OS. CONCLUSION: In this update, the rate of biochemical relapses increased
      compared with our previous data. Compared to similar studies, we found a
      remarkably low rate of PC-related deaths. Our data support early initiation of
      SRT. However, this treatment strategy, triggered by very low PSA levels, could
      carry the risk of overtreatment in at least a subset of patients.

PMID- 24577134
TI  - Treatment of giant cellulitis-like Sweet syndrome with dapsone.

PMID- 24577133
TI  - Prognostic significance of Ki67 proliferation index, HIF1 alpha index and
      microvascular density in patients with non-small cell lung cancer brain
      metastases.
AB  - BACKGROUND: Survival upon diagnosis of brain metastases (BM) in patients with non
      small cell lung cancer (NSCLC) is highly variable and established prognostic
      scores do not include tissue-based parameters. METHODS: Patients who underwent
      neurosurgical resection as first-line therapy for newly diagnosed NSCLC BM were
      included. Microvascular density (MVD), Ki67 tumor cell proliferation index and
      hypoxia-inducible factor 1 alpha (HIF-1 alpha) index were determined by
      immunohistochemistry. RESULTS: NSCLC BM specimens from 230 patients (151 male, 79
      female; median age 56 years; 199 nonsquamous histology) and 53/230 (23.0%)
      matched primary tumor samples were available. Adjuvant whole-brain radiation
      therapy (WBRT) was given to 153/230 (66.5%) patients after neurosurgical
      resection. MVD and HIF-1 alpha indices were significantly higher in BM than in
      matched primary tumors. In patients treated with adjuvant WBRT, low BM HIF-1
      alpha expression was associated with favorable overall survival (OS), while among
      patients not treated with adjuvant WBRT, BM HIF-1 alpha expression did not
      correlate with OS. Low diagnosis-specific graded prognostic assessment score (DS
      GPA), low Ki67 index, high MVD, low HIF-1 alpha index and administration of
      adjuvant WBRT were independently associated with favorable OS. Incorporation of
      tissue-based parameters into the commonly used DS-GPA allowed refined
      discrimination of prognostic subgroups. CONCLUSION: Ki67 index, MVD and HIF-1
      alpha index have promising prognostic value in BM and should be validated in
      further studies.

PMID- 24577136
TI  - Antisense oligonucleotides targeting parasite inositol 1,4,5-trisphosphate
      receptor inhibits mammalian host cell invasion by Trypanosoma cruzi.
AB  - Chagas disease is caused by an intracellular parasitic protist, Trypanosoma
      cruzi. As there are no highly effective drugs against this agent that also
      demonstrate low toxicity, there is an urgent need for development of new drugs to
      treat Chagas disease. We have previously demonstrated that the parasite inositol
      1,4,5-trisphosphate receptor (TcIP3R) is crucial for invasion of the mammalian
      host cell by T. cruzi. Here, we report that TcIP3R is a short-lived protein and
      that its expression is significantly suppressed in trypomastigotes. Treatment of
      trypomastigotes, an infective stage of T. cruzi, with antisense oligonucleotides
      specific to TcIP3R deceased TcIP3R protein levels and impaired trypomastigote
      invasion of host cells. Due to the resulting instability and very low expression
      level of TcIP3R in trypomastigotes indicates that TcIP3R is a promising target
      for antisense therapy in Chagas disease. 

PMID- 24577138
TI  - Novel tandem synthesis of bis(MU-NN'-tetrazolate) bridged dinuclear nickel(ii)
      Schiff base complex via [3 + 2] cyclo-addition at ambient condition.
AB  - A novel bis(MU-NN'-tetrazolate) bridged centrosymmetric dinuclear nickel(ii)
      Schiff base complex [Ni2(L)2(PTZ)2].2H2O.2CH3CN (HL is a tridentate Schiff base,
      2-((2-(ethylamino)ethylimino)methyl)-6-methoxyphenol and HPTZ is 5
      pyrazinyltetrazole) has been synthesized via [3 + 2] cyclo-addition reaction of 2
      cyanopyrazine and sodium azide in presence of nickel(ii) acetate tetrahydrate and
      HL. The structure of the complex is confirmed by single crystal X-ray diffraction
      analysis. The combination of H-bonding and C-Hpi interactions creates a 3(6)-hxl
      topological supramolecular network. The acetonitrile molecules are encapsulated
      as a hydrophobic guest within the 2D supramolecular network. 

PMID- 24577137
TI  - Adverse socioeconomic position during the life course is associated with multiple
      sclerosis.
AB  - BACKGROUND: Adverse socioeconomic position (SEP) in childhood and adulthood is
      associated with a proinflammatory phenotype, and therefore an important exposure
      to consider for multiple sclerosis (MS), a complex neuroinflammatory autoimmune
      disease. The objective was to determine whether SEP over the life course confers
      increased susceptibility to MS. METHODS: 1643 white, non-Hispanic MS case and
      control members recruited from the Kaiser Permanente Medical Care Plan, Northern
      California Region, for which comprehensive genetic, clinical and environmental
      exposure data have been collected were studied. Logistic regression models
      investigated measures of childhood and adulthood SEP, and accounted for effects
      due to established MS risk factors, including HLA-DRB1*15:01 allele carrier
      status, smoking history, history of infectious mononucleosis, family history of
      MS and body size. RESULTS: Multiple measures of childhood and adulthood SEP were
      significantly associated with risk of MS, including parents renting versus owning
      a home at age 10: OR=1.48, 95% CI 1.09 to 2.02, p=0.013; less than a college
      education versus at least a college education based on parental household:
      OR=1.28, 95% CI 1.01 to 1.63, p=0.041; low versus high life course SEP: OR=1.50,
      95% CI 1.09 to 2.05, p=0.012; and low versus high social mobility: OR=1.74, 95%
      CI 1.27 to 2.39, p=5.7*10(-4). CONCLUSIONS: Results derived from a population
      representative case-control study provide support for the role of adverse SEP in
      MS susceptibility and add to the growing evidence linking lower SEP to poorer
      health outcomes. Both genetic and environmental contributions to chronic
      conditions are important and must be characterised to fully understand MS
      aetiology.

PMID- 24577139
TI  - Are genes connected with homocysteine metabolism associated with bipolar
      disorder?
AB  - BACKGROUND: Increased levels of homocysteine have been observed in various
      psychiatric disorders, among them in schizophrenia, depression and bipolar mood
      disorder. Of the genes connected with homocysteine metabolism, some studies have
      found an association between polymorphism of the methylenetetrahydrofolate
      reductase (MTHFR) gene and bipolar disorder. The aim of this study was to
      investigate a possible association between 5 polymorphisms of 4 genes coding
      enzymes of homocysteine metabolism and bipolar disorder. METHOD: A total of 120
      patients with bipolar disorder (24 male, 96 female) and 167 subjects from the
      general population (81 male, 86 female) were included in the study. Genotyping
      was performed for the C677T (rs1801133) and A1298C (rs1801131) polymorphisms of
      the MTHFR gene, for the T833C polymorphism (rs5742905) of the cystathionine-beta
      synthase (CBS) gene, for the A2756G polymorphism (rs1805087) of the homocysteine
      methyltransferase gene, and for the A66G polymorphism (rs1801394) of the
      methionine synthase reductase (MTRR) gene. RESULTS: An association with bipolar
      disorder was found for the T833C polymorphism (rs5742905) of the CBS gene.
      However, in the patient sample, the genotypes of this polymorphism were not in
      Hardy-Weinberg equilibrium. No relationship to bipolar disorder was obtained for
      the remaining polymorphisms studied. CONCLUSIONS: These results are the first
      suggesting a possible association between T833C polymorphism (rs5742905) of the
      CBS gene and bipolar disorder. We were unable to confirm an association between
      bipolar disorder and C677T polymorphism (rs1801133) of the MTHFR gene, as
      suggested in some previous studies.

PMID- 24577142
TI  - Luminescent metal-organic frameworks for chemical sensing and explosive
      detection.
AB  - Metal-organic frameworks (MOFs) are a unique class of crystalline solids
      comprised of metal cations (or metal clusters) and organic ligands that have
      shown promise for a wide variety of applications. Over the past 15 years,
      research and development of these materials have become one of the most intensely
      and extensively pursued areas. A very interesting and well-investigated topic is
      their optical emission properties and related applications. Several reviews have
      provided a comprehensive overview covering many aspects of the subject up to
      2011. This review intends to provide an update of work published since then and
      focuses on the photoluminescence (PL) properties of MOFs and their possible
      utility in chemical and biological sensing and detection. The spectrum of this
      review includes the origin of luminescence in MOFs, the advantages of luminescent
      MOF (LMOF) based sensors, general strategies in designing sensory materials, and
      examples of various applications in sensing and detection. 

PMID- 24577143
TI  - A single-molecule approach to explore binding, uptake and transport of cancer
      cell targeting nanotubes.
AB  - In the past decade carbon nanotubes (CNTs) have been widely studied as a
      potential drug-delivery system, especially with functionality for cellular
      targeting. Yet, little is known about the actual process of docking to cell
      receptors and transport dynamics after internalization. Here we performed single
      particle studies of folic acid (FA) mediated CNT binding to human carcinoma cells
      and their transport inside the cytosol. In particular, we employed molecular
      recognition force spectroscopy, an atomic force microscopy based method, to
      visualize and quantify docking of FA functionalized CNTs to FA binding receptors
      in terms of binding probability and binding force. We then traced individual
      fluorescently labeled, FA functionalized CNTs after specific uptake, and created
      a dynamic 'roadmap' that clearly showed trajectories of directed diffusion and
      areas of nanotube confinement in the cytosol. Our results demonstrate the
      potential of a single-molecule approach for investigation of drug-delivery
      vehicles and their targeting capacity. 

PMID- 24577144
TI  - Tamoxifen treatment for pubertal gynecomastia in two siblings with partial
      androgen insensitivity syndrome.
AB  - BACKGROUND: Although tamoxifen has been shown to be fairly safe and effective for
      idiopathic pubertal gynecomastia, it remains unknown whether it is also
      beneficial for gynecomastia associated with endocrine disorders. Here, we report
      the effect of tamoxifen on pubertal gynecomastia in 2 siblings with partial
      androgen insensitivity syndrome (PAIS). CASE REPORTS: Cases 1 and 2 presented
      with persistent pubertal gynecomastia at 13 and 16 years of age, respectively.
      Physical examinations revealed breast of Tanner stage 3 and normal male-type
      external genitalia in both cases. Clinical features such as female-type pubic
      hair and borderline small testis indicated mildly impaired masculinization.
      RESULTS: Molecular analysis identified a previously reported p.Arg789Ser mutation
      in the androgen receptor gene (AR) in the 2 cases. Two months of oral
      administration of tamoxifen ameliorated gynecomastia to Tanner stage 2 with no
      adverse events. Additional treatment with testosterone enanthate showed
      negligible effects on body hair and penile length. Hormone values of the 2 cases
      during tamoxifen treatment remained similar to those in previously reported
      untreated patients with PAIS. CONCLUSION: The results indicate that tamoxifen was
      effective in treating pubertal gynecomastia in these 2 patients with PAIS and may
      be considered as a therapeutic option in this situation pending further studies.

PMID- 24577145
TI  - Lithium dosing equations: are they accurate?
AB  - BACKGROUND: Several equations are used to predict lithium doses necessary to
      attain therapeutic serum concentrations. A number of studies have evaluated these
      equations; however, few equations were compared simultaneously. OBJECTIVE: To
      assess the accuracy and precision of published dosing equations in predicting
      daily lithium doses and to evaluate if pertinent laboratory tests were performed
      prior to initiation. METHODS: A retrospective analysis was performed of patients
      who received lithium at the Medical University of South Carolina Institute of
      Psychiatry between July 2010 and July 2012. Using dosing equations, expected
      lithium doses were calculated based on corresponding serum concentrations
      identified in patient charts. Expected doses were then compared with actual
      lithium doses. The primary end point was to assess the accuracy and precision of
      dosing equations using mean differences in daily lithium doses and standard
      deviations. Secondary end points included presence of pertinent laboratory tests
      and use of concomitant interacting drugs . RESULTS: Of 155 patients identified,
      59 were eligible for analysis. Equations developed by Abou-Auda et al and Pepin
      et al did not predict doses that were significantly different from actual doses.
      Conversely, equations by Jermain et al, Terao et al, and Zetinet al did predict
      statistically different doses. CONCLUSIONS: Abou-Auda et al developed a
      predictive lithium dosing equation that was more accurate than equations
      developed by Jermain et al, Terao et al, and Zetin et al and more precise than
      the Pepin et al equation. Further study evaluating the influence of equations on
      clinical outcomes is warranted.

PMID- 24577146
TI  - Serotonin-norepinephrine reuptake inhibitors for the management of chemotherapy
      induced peripheral neuropathy.
AB  - OBJECTIVE: To review the literature evaluating serotonin-norepinephrine reuptake
      inhibitors (SNRIs) for chemotherapy-induced peripheral neuropathy (CIPN). DATA
      SOURCES: A PubMed search (1966-January 2014) was performed using the key terms
      serotonin-norepinephrine reuptake inhibitor, desvenlafaxine, duloxetine,
      milnacipran, venlafaxine, chemotherapy, and peripheral neuropathy. Bibliographies
      of select articles were examined for additional references and abstracts. STUDY
      SELECTION AND DATA EXTRACTION: Case reports and clinical trials published in
      English and conducted in humans were identified. All reports and trials
      evaluating a SNRI for the treatment of CIPN were included; 4 case reports, 1 open
      label study, and 2 randomized controlled trials were identified for review. DATA
      SYNTHESIS: At present, no medications are approved for the treatment for CIPN.
      Emerging evidence suggests that venlafaxine and duloxetine may be effective for
      treating CIPN. Results of select trials report that these medications not only
      decrease pain but also relieve symptoms of numbness and tingling and improve the
      functional status and quality of life of patients suffering from CIPN.
      CONCLUSIONS: Evidence to support venlafaxine and duloxetine for the treatment of
      CIPN from oxaliplatin- or paclitaxel-based regimens is promising. Unfortunately,
      direct comparisons between venlafaxine and duloxetine do not exist, so definitive
      conclusions about which agent is preferred cannot be made. However, the breadth
      of data with duloxetine is larger, suggesting that it may be prudent to consider
      duloxetine first when choosing a SNRI for CIPN treatment. More robust trials are
      needed to establish their optimal place in therapy with regard to patient
      population, timing of therapy, dosing, and treatment duration.

PMID- 24577147
TI  - Response to "evaluation of dabigatran exposures reported to poison control
      centers".

PMID- 24577148
TI  - Severe tinnitus induced by off-label baclofen.
AB  - OBJECTIVE: The gamma-aminobutyric acid type B (GABA-B) receptor agonist baclofen
      is approved for spasticity up to the dose of 80 mg/d. Recently, off-label use of
      high-dose baclofen (HDB), up to 400 mg/d, has been increasing for treating
      alcohol use disorders (AUDs), although the efficacy and safety profiles of HDB
      are relatively unknown. We report 2 cases of tinnitus in patients treated with
      HDB for AUD. CASE SUMMARIES: The first case concerns a 60-year-old man who
      reported tinnitus when he reached a 180 mg/d dose of baclofen after 3 months of
      treatment. Tinnitus persisted until the dose was reduced to 90 mg/d. The second
      case concerns a 45-year-old woman who presented with tinnitus when she reached a
      210 mg/d dose of baclofen after 4 months of treatment. Tinnitus persisted until
      the dose was reduced to 60 mg/d. DISCUSSION: Using the Naranjo scale,
      imputability to baclofen was considered probable in both cases. GABA-B receptors
      have been reported to be implicated in both the etiology and the treatment of
      tinnitus. There may be an individual susceptibility to develop tinnitus under
      baclofen therapy because of some GABA-B genetic polymorphisms that remain to be
      determined. CONCLUSION: HDB may be responsible for the occurrence of severe
      tinnitus, possibly in a dose-dependent manner. This appears to be coherent with
      the previously known involvement of GABA-B receptors in the pathophysiology of
      tinnitus.

PMID- 24577149
TI  - Fertility-preserving treatment in young women with endometrial adenocarcinoma: a
      long-term cohort study.
AB  - OBJECTIVE: Growing evidence suggests that fertility-preserving treatment is
      feasible for young women with early-stage, low-grade endometrial carcinoma.
      However, published data on their long-term outcomes and prognostic factors remain
      scanty. We aimed to investigate the outcomes of young women receiving fertility
      preserving treatment. METHODS: Between 1991 and 2010, the outcomes of young women
      with grade 1 endometrioid endometrial carcinoma at presumed stage IA (without
      myometrial invasion) who underwent fertility-preserving treatment of megestrol
      acetate 160 mg/d with or without other hormonal agents were retrospectively
      analyzed. RESULTS: We identified 37 eligible patients (median age, 32 years;
      range, 18-40 years). The median follow-up time was 78.6 months (range, 19.1-252.8
      months). Complete response (CR) lasting more than 6 months was achieved in 30
      (81.1%) women. Responders were significantly younger than nonresponders (P =
      0.032). Of the 30 women who had a CR, 15 (50.0%) had disease recurrence. The 5-,
      10-, and 15-year cumulative recurrence-free survival rates were 51.0%, 51.0%, and
      34.0%, respectively. Notably, those recurred were significantly older (P =
      0.003), and the time to CR was significantly longer (P = 0.043) than those
      without recurrence. One patient developed late recurrences at 156 months, and 2
      patients developed ovarian metastasis (6 and 137 months from diagnosis). All the
      patients are currently alive. CONCLUSIONS: This study demonstrates the
      feasibility of high-dose megestrol acetate-based therapy for fertility
      preservation. The substantial risk of late recurrences highlights the need for
      long-term follow-up studies of large sample sizes with in-depth tumor and host
      molecular signatures.

PMID- 24577150
TI  - Trends in pre-liver transplant screening for cholangiocarcinoma among patients
      with primary sclerosing cholangitis.
AB  - BACKGROUND: Cholangiocarcinoma (CCA) is the most common hepatobiliary malignancy
      complicating primary sclerosing cholangitis (PSC). Unfortunately, timely
      diagnosis of CCA in PSC patients remains challenging. AIM: To investigate the
      strategies among liver centers regarding pre-transplant screening for CCA in
      patients with PSC. METHODS: An online survey was returned from 46 US transplant
      centers, inquiring on the frequency of screening, the use of specific tests, or
      tactical approaches to high-grade dysplasia (HGD) or CCA. RESULTS: Most centers
      screen their PSC patients for CCA prior to orthotopic liver transplantation (OLT)
      (89%). Serum carbohydrate antigen 19-9 and magnetic resonance
      cholangiopancreatography are first-line screening tools (93 and 84%
      respectively). Endoscopic retrograde cholangiopancreatography with biliary
      brushings is routinely performed in only 30% of the centers. In the case of HGD,
      61% would choose close monitoring. In the event of non-resectable CCA, 37% have
      an OLT protocol, 33% resort to palliative treatment and the remaining 30% make an
      outside referral. Finally, half the participating centers perform CCA
      surveillance among their listed PSC patients every 6 months. CONCLUSION:
      Screening for CCA among PSC patients prior to OLT varies greatly among centers.
      Serum carbohydrate antigen 19-9 and magnetic resonance cholangiopancreatography
      are widely used. HGD warrants surveillance rather than intervention among most
      experts. Protocolized chemoradiation followed by OLT has yet to become a widely
      accepted approach. The very poor survival of PSC patients who develop CCA
      underlines the importance of an effective and universally accepted screening
      process that will aid in its earlier detection.

PMID- 24577152
TI  - Three molybdophosphates based on Strandberg-type anions and Zn(II)-H2biim/H(2)O
      subunits: syntheses, structures and catalytic properties.
AB  - Three new inorganic-organic hybrid compounds based on Strandberg-type anions and
      Zn(ii)-H2biim/H2O subunits, namely
      {H4(H2biim)3}[Zn(H2biim)(H3biim)(H2O)(HP2Mo5O23)]2.3H2O (1), {H9(H2biim)7}[(MU
      biim){(Zn(H2O)2)0.5(HP2Mo5O23)}2].7H2O (2) and
      {H7(H2biim)7}[Zn(H2biim)(H2O)2(HP2Mo5O23)][H2P2Mo5O23].8H2O (3) (H2biim = 2,2'
      biimidazole), have been synthesized in aqueous solutions and characterized. They
      were also used as efficient and reusable catalysts for the protection of carbonyl
      compounds. Their fascinating structural features are that mono Zn(ii)-supporting
      biphosphopentamolybdate ({P2Mo5}) clusters exist in their crystal structures, and
      the nitrogen donor ligand H2biim exhibits three different coordination modes in
      these three compounds, respectively: for 1, two 2,2'-biimidazole molecules, as
      mono- and bidentate ligands coordinate to the same Zn(ii) ion; for 2, one bi
      negative tetradentate ligand MU-biim bridges two Zn(ii) ions, while for 3, one
      neutral bidentate H2biim ligand links one Zn(ii) ion. Most importantly, compounds
      1-3 represent the first example where Strandberg-type POMs are used as acid
      catalysts in an organic reaction. 

PMID- 24577151
TI  - Integrating systems biology sources illuminates drug action.
AB  - There are significant gaps in our understanding of the pathways by which drugs
      act. This incomplete knowledge limits our ability to use mechanistic molecular
      information rationally to repurpose drugs, understand their side effects, and
      predict their interactions with other drugs. Here, we present DrugRouter, a novel
      method for generating drug-specific pathways of action by linking target genes,
      disease genes, and pharmacogenes using gene interaction networks. We construct
      pathways for more than a hundred drugs and show that the genes included in our
      pathways (i) co-occur with the query drug in the literature, (ii) significantly
      overlap or are adjacent to known drug-response pathways, and (iii) are adjacent
      to genes that are hits in genome-wide association studies assessing drug
      response. Finally, these computed pathways suggest novel drug-repositioning
      opportunities (e.g., statins for follicular thyroid cancer), gene-side effect
      associations, and gene-drug interactions. Thus, DrugRouter generates hypotheses
      about drug actions using systems biology data. 

PMID- 24577153
TI  - Longitudinal melanonychia of the toenail.

PMID- 24577155
TI  - Regulation and localization of transient receptor potential melastatin 2 in rat
      uterus.
AB  - The transient receptor potential channels are membrane-binding proteins that are
      nonselectively permeable for cations, such as Ca(2+) and Mg(2+), in numerous
      mammalian cells. The extracellular or intracellular ions play key roles in
      physiological functions including muscle contraction, cytokine production,
      insulin release, and apoptosis. Although transient receptor potential melastatin
      (TRPM) channels are implicated in nonreproductive tissues, the presence of TRPM2
      has been reported in endometrium of uterus. To examine whether the expression of
      TRPM2 gene in uterus is due to gonadal steroid hormones or hormone-independent
      effect, the uterine TRPM2 gene was monitored in uterus of mature rat during
      estrous cycle and of immature rat after treatment with gonadal steroid estrogen
      (E2), progesterone (P4) with/without estrogen receptor antagonist Imperial
      Chemical Industries (ICI) 182780. We examined real-time polymerase chain
      reaction, Western blot, and immunohistochemistry to demonstrate the expression
      and localization of the uterine TRPM2 gene. The level of TRPM2 messenger RNA and
      protein are dramatically induced at proestrus, then dropped to base line levels
      at metestrus, and restored its level at diestrus. The results imply that uterine
      TRPM2 expression levels are regulated by gonadal steroid hormone E2. Moreover,
      the E2-induced TRPM2 expression is inhibited by cotreatment with ICI 182780 or
      P4. Furthermore, the immune-reactive TRPM2 is observed in myometrium and stromal
      cell of endometrium and also showed alterations in TRPM2 expression during estrus
      cycle. This study suggests that TRPM2 may be involved in calcium absorption or
      uterine contraction and the latter may be related to implantation or labor by
      endogenous sex steroid hormones.

PMID- 24577156
TI  - Evaluation of the Macula, Retinal Nerve Fiber Layer, and Choroid Thickness in
      Women With Polycystic Ovary Syndrome Using Spectral-Domain Optical Coherence
      Tomography.
AB  - This study aimed to investigate the macular, retinal nerve fiber layer (RNFL),
      and choroid thickness alterations using spectral-domain optical coherence
      tomography in women with polycystic ovary syndrome (PCOS) and to compare them
      with healthy reproductive-age women volunteers. Study group consisted of 64
      patients with PCOS and control group consisted of 60 healthy volunteers. There
      was a statistically significant difference between PCOS and control groups for
      choroid thickness (P < .001). Fovea center thickness and temporal inner macula
      were significantly thinner in the PCOS group than those in the healthy control
      group (P = .009 and P = .033, respectively). Contrary to these findings, nasal
      outer macula (NOM) and temporal outer macula (TOM) were statistically thicker in
      the PCOS group than those in the control group (P = .001 and P < .001,
      respectively). Increased choroid thickness and RNFL may lead to increase in both
      retinal volume and retinal thickness in the peripheral side of the retina.
      Therefore, NOM and TOM region can be accepted sensitive areas in patients with
      PCOS.

PMID- 24577154
TI  - Impact of delivery models on understanding genomic risk for type 2 diabetes.
AB  - BACKGROUND: Genetic information, typically communicated in-person by genetic
      counselors, can be challenging to comprehend; delivery of this information online
      -as is becoming more common--has the potential of increasing these challenges.
      METHODS: To address the impact of the mode of delivery of genomic risk
      information, 300 individuals were recruited from the general public and
      randomized to receive genomic risk information for type 2 diabetes mellitus in
      person from a board-certified genetic counselor or online through the testing
      company's website. RESULTS: Participants were asked to indicate their genomic
      risk and overall lifetime risk as reported on their test report as well as to
      interpret their genomic risk (increased, decreased, or same as population). For
      each question, 59% of participants correctly indicated their risk. Participants
      who received their results in-person were more likely than those who reviewed
      their results on-line to correctly interpret their genomic risk (72 vs. 47%, p =
      0.0002) and report their actual genomic risk (69 vs. 49%, p = 0.002).
      CONCLUSIONS: The delivery of personal genomic risk through a trained health
      professional resulted in significantly higher comprehension. Therefore, if the
      online delivery of genomic test results is to become more widespread, further
      evaluation of this method of communication may be needed to ensure the effective
      presentation of results to promote comprehension.

PMID- 24577158
TI  - Role of elevated cancer antigen 19-9 in women with mature cystic teratoma.
AB  - The objective of this study was to determine how often an elevated cancer antigen
      (CA) 19-9 (>= 37 U/mL) was present during the preoperative evaluation of women
      with a mature cystic teratoma (MCT). This was a retrospective, consecutive case
      series (N = 139) of histologically proven MCT treated at Montefiore Medical
      Center from 1997 to 2008. Data were analyzed for patient and tumor
      characteristics, tumor markers (CA 19-9, CA 125, and carcinoembryonic antigen
      [CEA]), preoperative imaging, and procedure. CA 19-9 was elevated in 37.4% of
      patients. Elevated CA 19-9 was not significantly associated with age, race, CA
      125 (>=35 U/mL), CEA (>=5 ng/mL), MCT size, or the presence of bilateral MCTs. Of
      the patients, 59% were >=40 years old. Age <40 years was associated with
      cystectomy rather than oophorectomy (P < .001), regardless of CA 19-9 (P = .09).
      Elevated preoperative CA 19-9 in patients with MCT was associated with increased
      preoperative computed tomography (P = .04).

PMID- 24577157
TI  - RIFLE classification and mortality in obstetric patients admitted to the
      intensive care unit with acute kidney injury: a 3-year prospective study.
AB  - OBJECTIVE: This study is to assess the correlation of risk, injury, failure,
      loss, and end-stage renal failure (RIFLE) classification with hospital mortality
      in intensive care unit (ICU) obstetric patients and to evaluate the relation of
      acute kidney injury (AKI) to other risk factors. METHODS: The 4 stages of RIFLE
      (nonacute renal failure, risk, injury, and failure) were scored from 0 to 3
      points, respectively. The prognostic performance of the RIFLE score was compared
      to the general ICU models. RESULTS: AKI occurred in 30 (5.88%) of patients
      admitted to ICU. The main causes of AKI were hemolysis, elevated liver enzymes,
      and low platelet syndrome 13 (43%), pregnancy-related hypertension 9 (30%),
      puerperal sepsis 3 (10%), abruption placentae 2 (6.6%), disseminated
      intravascular coagulopathy 2 (6.6%), and anesthetic complications 1 (3.3%).
      According to the RIFLE criteria, patients were classified into Risk (3.3%),
      Injury (16.6%), Failure (33.3%), and Loss (46.6%). Maternal mortality from total
      ICU admission occurred in 51 (10%) cases, of these 16 (31.3%) cases were due to
      AKI. Independent risk factors associated with mortality were hyperbilirubinemia,
      low levels of HCO3, and RIFLE. Receiver-operator characteristic curves for ICU
      patients according to RIFLE score showed area under the curve = 0.824.
      CONCLUSION: The RIFLE classification system could predict the risk of mortality
      from AKI in obstetric ICU patients and mortality was positively associated with
      high RIFLE classes.

PMID- 24577159
TI  - Monolithic graphene oxide sheets with controllable composition.
AB  - Graphene oxide potentially has multiple applications and is typically prepared by
      solution-based chemical means. To date, the synthesis of a monolithic form of
      graphene oxide that is crucial to the precision assembly of graphene-based
      devices has not been achieved. Here we report the physical approach to produce
      monolithic graphene oxide sheets on copper foil using solid carbon, with tunable
      oxygen-to-carbon composition. Experimental and theoretical studies show that the
      copper foil provides an effective pathway for carbon diffusion, trapping the
      oxygen species dissolved in copper and enabling the formation of monolithic
      graphene oxide sheets. Unlike chemically derived graphene oxide, the as
      synthesized graphene oxide sheets are electrically active, and the oxygen-to
      carbon composition can be tuned during the synthesis process. As a result, the
      resulting graphene oxide sheets exhibit tunable bandgap energy and electronic
      properties. Our solution-free, physical approach may provide a path to a new
      class of monolithic, two-dimensional chemically modified carbon sheets. 

PMID- 24577160
TI  - Postoperative pulmonary complications after surgery in patients with interstitial
      lung disease.
AB  - BACKGROUND: Patients with interstitial lung disease (ILD) have a high incidence
      of postoperative pulmonary complications (PPCs) after lung resection, but there
      is little data about these complications in ILD after other types of surgery.
      OBJECTIVES: The aim of this study was to examine the characteristics and
      predictors of PPCs after major surgery in patients with ILD. METHODS: We included
      336 patients with ILD who underwent major surgery between January 2005 and
      December 2010 at two tertiary hospitals in Korea. All types of surgery that had
      been performed under general anesthesia were included. Demographic
      characteristics, preoperative lung function, and operative conditions including
      anesthesia time and estimated blood loss were compared between patients with and
      without PPCs. RESULTS: PPCs occurred in 37 patients (11%). Thirteen patients
      developed pneumonia, the most common PPC, and 11 had acute exacerbation of ILD.
      In multivariable analysis, BMI <23 (OR = 2.488, 95% CI: 1.084-5.710, p = 0.031),
      emergency surgery (OR = 23.992, 95% CI: 2.629-218.949, p = 0.005), lung surgery
      (OR = 5.090, 95% CI: 1.391-18.628, p = 0.014), and longer anesthesia time (OR =
      1.595, 95% CI: 1.143-2.227, p = 0.006) were statistically significant risk
      factors. CONCLUSIONS: The incidence of PPCs detected over all surgeries was not
      as high as that reported for lung surgery alone in ILD patients. Lower BMI,
      emergency surgery, lung surgery, and longer anesthesia time were risk factors.
      Operative conditions as well as lung function should be considered in
      preoperative planning and management for ILD patients undergoing major surgery.

PMID- 24577161
TI  - The acute hospital setting as a place of death and final care: a qualitative
      study on perspectives of family physicians, nurses and family carers.
AB  - While the focus of end-of-life care research and policy has predominantly been on
      'death in a homelike environment', little is known about perceptions of the acute
      hospital setting as a place of final care or death. Using a qualitative design
      and constant comparative analysis, the perspectives of family physicians, nurses
      and family carers were explored. Participants generally perceived the acute
      hospital setting to be inadequate for terminally ill patients, although they
      indicated that in some circumstances it might be a 'safe haven'. This implies
      that a higher quality of end-of-life care provision in the acute hospital setting
      needs to be ensured, preferably by improving communication skills. At the same
      time alternatives to the acute hospital setting need to be developed or expanded.

PMID- 24577162
TI  - Could behavioral medicine lead the web data revolution?

PMID- 24577163
TI  - The Impact of Positive Margins on Outcome Among Patients With Gastric Cancer
      Treated With Radiation.
AB  - OBJECTIVES: Positive surgical margins have been associated with worse outcomes in
      gastric cancer patients. We evaluated the impact of positive margins in a modern
      cohort treated with radiotherapy. METHODS: We performed a multi-institutional
      retrospective analysis of patients treated from 1998 through 2010. All underwent
      definitive surgery and were followed up for recurrence and survival. We assessed
      associations with positive margins using the log-rank tests and Cox proportional
      hazard models. RESULTS: We identified 91 patients with a median follow-up of 42
      months. Seven received radiation before surgery; the remainder were treated
      postoperatively. Epirubicin-based chemotherapy was given to 8 patients
      perioperatively and 25 postoperatively. Nineteen had positive margins (21%),
      including 25% of patients who received chemotherapy perioperatively. All patients
      who received neoadjuvant radiotherapy had negative margins. There were 41
      recurrences and 44 deaths. Positive margins were associated with increased
      recurrence risk after adjusting for other factors (hazard ratio=2.8, P=0.01). In
      addition, median survival with positive margins was 31 months as compared with 77
      months after complete resection (P=0.13). CONCLUSIONS: Positive margins were
      associated with recurrence despite aggressive multimodality therapy including
      radiotherapy and the selective use of chemotherapy. Thus, additional
      consideration is warranted for strategies such as neoadjuvant chemoradiation
      intended to facilitate complete resection.

PMID- 24577165
TI  - Is proton-beam therapy better than intensity-modulated radiation therapy for
      prostate cancer?

PMID- 24577166
TI  - Meningioma in Breast Cancer Patients: Population-based Analysis of
      Clinicopathologic Characteristics.
AB  - OBJECTIVES: Although an association between meningioma and breast cancer (BC) has
      been postulated, clear mechanisms remain obscure. By conducting population-based
      analyses in women with both BC and meningioma, hypothesis-generating causal links
      were pursued. METHODS: Using the US SEER 18 registry (2004 to 2009),
      clinicopathologic and demographic characteristics from cohorts of women with only
      BC (n=279,821) or meningioma (n=19,570) diagnoses were compared with 412 women
      with both diagnoses (BC-meningioma). RESULTS: BC diagnosis preceded meningioma by
      >2 months in 48% of women; 20% had synchronous (within 2 mo) disease. Median
      meningioma size was 1.9 and 2.4 cm in the BC-meningioma and meningioma cohorts,
      respectively (P=0.0009). Among BC-meningioma patients, meningioma size was
      similar whether diagnosed >2 months prior, synchronously, or >2 months after BC.
      Meningioma was pathologically confirmed in 38% of BC-meningioma and 51% of
      meningioma patients. Distribution of BC histologies was comparable in patients
      with and without meningioma, with ductal type predominating (80% in BC
      meningioma, 83% in BC). Although hormone receptor status of invasive BC was not
      significantly different between BC-meningioma and BC groups, the BC-meningioma
      cohort had fewer women with ER+/PR+ in situ disease (P=0.006). BC stage among
      women with meningioma was more advanced versus women with BC only. CONCLUSIONS:
      Women with BC and meningioma have smaller-sized meningiomas and more advanced BCs
      compared with women having only 1 diagnosis. As there was no temporal
      relationship between size and latency between tumor diagnoses, the disparity in
      meningioma size between BC-meningioma and meningioma cohorts may have BC
      associated biological components that warrant further study.

PMID- 24577164
TI  - High-circulating Tie2 Is Associated With Pathologic Complete Response to
      Chemotherapy and Antiangiogenic Therapy in Breast Cancer.
AB  - INTRODUCTION: Vascular endothelial growth factor (VEGF) is a central mediator of
      angiogenesis in breast cancer. Research in antiangiogenic cancer treatment has
      been marked by the development of the monoclonal antibody bevacizumab, which
      targets VEGF in many solid tumors. As patients do not equally benefit from
      bevacizumab, it has become necessary to define the profile of patients who will
      benefit from the drug. MATERIALS AND METHODS: We have conducted a prospective
      phase II study in 39 patients using bevacizumab in breast cancer in the
      neoadjuvant setting, and found improved pathologic complete response (pCR) when
      bevacizumab was added to chemotherapy in patients with hormone receptor negative
      and invasive ductal carcinoma. Blood samples were collected at baseline and
      serially while patients were on treatment. Circulating angiogenesis-related
      proteins angiopoietin (ANG)1, ANG2, basic fibroblast growth factor, IL-1a, matrix
      metalloproteinase 9, platelet derived growth factor - BB, platelet endothelial
      cell adhesion molecule -1, Tie2, VEGF, and vascular endothelial growth factor
      receptor 2 were measured at baseline and during treatment. This correlative study
      was conducted to identify specific serum angiogenic factor profiles that might be
      associated with pCR in the neoadjuvant setting in breast cancer patients
      receiving bevacizumab and chemotherapy. RESULTS: Elevated baseline serum Tie2 and
      basic fibroblast growth factor were associated with pCR in response to this
      combination. Changes in serum levels of these proteins were seen during treatment
      but were not significantly different between the pCR and non-pCR groups.
      CONCLUSIONS: Baseline-circulating Tie2 levels may help distinguish patients who
      will have pCR from those who will not and may form the basis for future
      development of antiangiogenic therapy in breast cancer. Larger studies are needed
      to validate these findings. ClinicalTrials.gov Identifier: NCT00203502.

PMID- 24577167
TI  - Phase I Study of Pazopanib and Ixabepilone in Patients With Solid Tumors.
AB  - OBJECTIVES: Pazopanib is a tyrosine kinase inhibitor predominantly acting on
      tumor endothelium, and ixabepilone is a semisynthetic analog of epothilone B that
      promotes microtubule stabilization inducing tumor and tumor endothelial cell
      apoptosis. The purpose of this study was to determine the optimal tolerated dose
      (OTD) of the combination of pazopanib and ixabepilone for the treatment of
      metastatic previously treated solid tumors. METHODS: Dose escalation started at
      32 mg/m of ixabepilone and increased to 40 mg/m. Pazopanib was administered
      initially at 400 mg and escalated at 200 mg increments up to 800 mg.
      Pharmacokinetic analysis assessed effect of ixabepilone on pazopanib metabolism.
      Correlative studies evaluated changes in angiogenic cytokines. RESULTS: Thirty
      one patients (20 male and 11 female; median age, 58 y) with ECOG PS of 0 or 1
      were enrolled. Three patients had dose-limiting toxicities (fatigue and
      neutropenia) at dose level 2 (ixabepilone 40 mg/m and pazopanib 400 mg), and
      therefore the ixabepilone dose was decreased (32 mg/m) before escalating
      pazopanib to levels 3 and 4. One patient had a dose-limiting toxicity
      (thrombocytopenia) at dose level 4 (ixabepilone 32 mg/m and pazopanib 800 mg).
      Dose level 3 was determined to be the OTD (pazopanib 600 mg and ixabepilone 32
      mg/m). The most common toxicities were cytopenias. A significant decrease in the
      level of sE-selectin was associated with improvement in progression free
      survival. CONCLUSIONS: The OTD for combination of pazopanib and ixabepilone was
      established. There was no impact of ixabepilone on pazopanib pharmacokinetics.
      The relationship between sE-selectin and progression free survival warrants
      further investigation.

PMID- 24577168
TI  - Population-based Analysis of Treatment and Survival in Women Presenting With
      Brain Metastasis at Initial Breast Cancer Diagnosis.
AB  - PURPOSE: Brain metastasis at initial breast cancer diagnosis is rare. This study
      aims to evaluate the clinical characteristics of these patients and identify
      prognostic and treatment factors associated with improved survival. METHODS:
      Subjects were 35 women referred from 1996 to 2005 with newly diagnosed breast
      cancer with synchronous brain metastasis. Overall survival (OS) and brain
      progression-free survival were examined using Kaplan-Meier methods and compared
      between subgroups with different clinicopathologic and treatment characteristics
      using log-rank tests. RESULTS: Median age was 65 years. Whole-brain radiotherapy
      (WBRT) alone was used in 25 patients, surgical resection and postoperative WBRT
      in 5 patients, and no or unknown treatment in 5 patients. Patients who underwent
      cranial resection were more likely to have solitary brain metastasis (P=0.003)
      and no visceral involvement (P=0.006). Overall, median OS was 6.8 months and
      median brain progression-free survival was 6.5 months (range, 0.7 to 54 mo).
      Median OS were 15 months with surgery and postoperative WBRT, 5 months with WBRT
      alone, and 3 months with no brain treatment. Longer OS was observed with age
      below 65 years versus 65 years and above (11 vs. 5 mo, P=0.046), 0 to 1 versus
      >=2 sites of extracranial metastasis (10 vs. 3 mo, P=0.047), and diagnosis from
      2001 to 2005 versus 1996 to 2000 (10 vs. 3 mo, P=0.018). A trend toward improved
      OS was observed in patients with no visceral involvement (11 vs. 4 mo, P=0.09).
      CONCLUSIONS: In this unique cohort presenting with breast cancer and synchronous
      brain metastasis, longer survival were observed with young age, limited
      extracranial metastasis, and no visceral disease. These characteristics may be
      used to select candidates for more aggressive treatment.

PMID- 24577169
TI  - Polyangiitis overlap syndrome of granulomatosis with polyangiitis (Wegener's
      granulomatosis) and eosinophilic granulomatosis with polyangiitis (Churg-Strauss
      syndrome).
AB  - Polyangiitis overlap syndrome is defined as systemic vasculitis that cannot be
      classified into one of the well-defined vasculitic syndromes. In this report, a
      female patient who presented with vasculitis-like and asthmatic symptoms was
      diagnosed as having polyangiitis overlap syndrome of granulomatosis with
      polyangiitis (GPA; formerly known as Wegener's granulomatosis) and eosinophilic
      granulomatosis with polyangiitis (EGPA; formerly known as Churg-Strauss
      syndrome). The patient fulfilled the American College of Rheumatology diagnostic
      criteria for GPA and EGPA. She was successfully treated with immunosuppressants
      and steroids and has been in remission for 20 months. It is important to
      establish a proper diagnosis and introduce an appropriate treatment modality in
      patients with this rare and serious pathology to prevent irreversible organ
      damage. 

PMID- 24577170
TI  - Very late stent thrombosis following the placement of a crossing Y-stent with
      dual closed-cell stents for the coiling of a wide-necked aneurysm.
AB  - The crossing Y-stent technique is a viable option for coiling of wide-necked
      bifurcation aneurysms. However, little is known about the long-term impact of
      this technique. Very late (>1 year) stent thrombosis following the placement of a
      crossing Y-stent with dual closed-cell stents for the coiling of a wide-necked
      basilar tip aneurysm, which has not been reported to date, is described. 

PMID- 24577171
TI  - Maxillary molar distalization with first class appliance.
AB  - Non-extraction treatment has gained popularity for corrections of mild-to
      moderate class II malocclusion over the past few decades. The distalization of
      maxillary molars is of significant value for treatment of cases with minimal arch
      discrepancy and mild class II molar relation associated with a normal mandibular
      arch and acceptable profile. This paper describes our experience with a 16-year
      old female patient who reported with irregularly placed upper front teeth and
      unpleasant smile. The patient was diagnosed to have angles class II malocclusion
      with moderate maxillary anterior crowding, deep bite of 4 mm on a skeletal class
      II base with an orthognathic maxilla and retrognathic mandible and normal growth
      pattern. She presented an ideal profile and so molar distalization was planned
      with the first-class appliance. Molars were distalised by 8 mm on the right and
      left quadrants and class I molar relation achieved within 4 months. The space
      gained was utilised effectively to align the arch and establish a class I molar
      and canine relation. 

PMID- 24577172
TI  - Huge trichobezoar causing obstructive jaundice.
AB  - Trichobezoars are composed of hair or hair-like fibres that are commonly observed
      in the gastrointestinal tract of children and young women with psychiatric
      illnesses. Presentation of trichobezoars can be diverse. We report a case of a 29
      year-old woman who presented with obstructive jaundice and a large upper
      abdominal lump. She was diagnosed with post-traumatic stress disorder on
      psychiatric evaluation. She underwent exploratory laparotomy and a large
      trichobezoar was removed. Her postoperative course was uneventful and she was
      referred to the psychiatric department for further management. 

PMID- 24577173
TI  - Systemic lupus erythematosus mimicking lymphoma: the relevance of the clinical
      background in interpreting imaging studies.
AB  - Systemic lupus erythematosus (SLE) is known as the 'great imitator' mimicking a
      myriad of conditions often resulting in a delayed diagnosis. We report a case
      with multisite adenopathy radiologically suggestive of lymphoma who initially was
      referred to the 'Cancer of Unknown Primary' team. Following a re-evaluation of
      the case the patient was diagnosed with SLE and was started on appropriate
      therapy. Many conditions presenting to oncology may mimic cancer which needs to
      be borne in mind when assessing referred cases. 

PMID- 24577174
TI  - Limiting progressive hippocampal metabolic abnormalities after smoke inhalation
      injury.
AB  - A 46-year-old man had a smoke inhalation injury. Within 1 month, he developed
      neuropsychiatric problems including toxic encephalopathy, cognitive disorder,
      depression symptoms and personality change. From 3 to 14 years after the toxic
      inhalation injury, the patient received treatment with sertraline and
      methylphenidate. The (18)F-fluorodeoxyglucose positron emission tomography scan
      at 3 years after injury showed deterioration of glucose metabolism in the
      hippocampus and orbital frontal region; at 14 years after injury, the hippocampus
      had no significant change but the orbital frontal region had deterioration of
      glucose metabolism. It was hypothesised that sertraline may have provided
      selective hippocampal neuroprotection. Further study is justified to evaluate
      sertraline as a possible neuroprotective agent after smoke inhalation injury. 

PMID- 24577175
TI  - Solitary necrotic nodule of the liver: a very challenging diagnosis!
AB  - Solitary necrotic nodule of the liver is a rare entity of unknown aetiology. We
      describe the case of a 59-year-old woman reporting sporadic right upper quadrant
      pain. An abdominal CT scan revealed a liver nodule located in segment 4. The
      complementary investigation was unable to identify the neoplastic lesion, and its
      surgical resection was performed, with an uneventful recovery. Pathological
      examination revealed a 'solitary necrotic nodule of the liver.' The patient
      remains asymptomatic and free of recurrence 3 years after surgery. This case
      corroborates that despite the advances in liver imaging and biopsy, liver nodules
      are sometimes a diagnostic challenge; quite often, only its surgical resection
      allows a definitive diagnosis. 

PMID- 24577176
TI  - All that wheezes is not asthma.
AB  - A young woman was admitted with respiratory failure. Prior to her admission, she
      had been treated for clinical bronchial asthma for about 2 years for recurrent
      wheezing. Endotracheal intubation was difficult. A fibroptic bronchoscopy, while
      the patient was ventilated, revealed a central tracheal tumour compromising >90%
      of the tracheal lumen. The tumour was cored out during rigid bronchoscopy while
      ventilating the patient through tracheostomy. Histopathology of the tumour was
      suggestive of adenoid cystic carcinoma.

PMID- 24577177
TI  - Insulinoma: rare yet important.
AB  - We report our experience with six cases of insulinoma that were managed at our
      hospital between 2009 and 2013. Four patients were women and two men, with mean
      age of 43 years and mean duration of symptoms before diagnosis of 5.7 years.
      Biochemical confirmation was made in all cases and preoperative localisation was
      successful in two cases only. In the other four, intraoperative localisation was
      made. Enucleation was performed in four patients and distal pancreatectomy in the
      other two. The tumour was proved benign in all patients by histopathology.
      Postoperatively, all patients were asymptomatic during a follow-up period ranging
      from 9 months to 4 years and both serum glucose and insulin were normal during
      that period. We think that careful preoperative workup and skilful surgical
      techniques can end the prolonged suffering of patients with insulinomas with
      excellent results. 

PMID- 24577178
TI  - Primary tuberculosis of the thyroid gland: an unexpected cause of thyrotoxicosis.
AB  - We describe a 38-year-old Indian man who presented with a 2-week history of
      fever, night sweats and neck swelling who was found to be clinically thyrotoxic
      with a nodular goitre, tachycardia and high fever. Biochemical investigation
      revealed hyperthyroidism in association with deranged liver function tests and
      raised inflammatory markers. Ultrasound and CT scans of the neck revealed
      multinodular thyroid enlargement. He was considered most likely to have an acute
      infectious thyroiditis with a differential diagnosis of a toxic multinodular
      goitre and was started on carbimazole and antibiotics. He underwent fine needle
      aspiration of the thyroid which revealed necrotic cells and acid-fast bacilli,
      confirming a diagnosis of primary tuberculosis (TB) of the thyroid gland with no
      evidence of any other organ involvement on systemic imaging. He was started on TB
      therapy for 6 months and discharged with outpatient follow-up. Symptoms and
      biochemical markers subsequently resolved. 

PMID- 24577179
TI  - Herpes simplex keratitis-induced endophthalmitis in a patient with AIDS with
      disseminated tuberculosis.
AB  - We present the case of a 42-year-old man with AIDS who had lost complete vision
      of his left eye for the past 15 days. MRI and brightness scan ultrasonography
      were performed on his eyes that suggested of endophthalmitis with dendritic
      involvement in the left eye. Viral DNA PCR was performed in aqueous humour sample
      that confirmed the presence of herpes simplex virus and showed a negative result
      for cytomegalovirus. The patient was treated with a high dose of oral acyclovir
      for 10 days and long-term topical acyclovir. Neodymium-doped yttrium aluminum
      garnet procedure was performed to clear up the cornea, and intraocular pressure
      was controlled with brimonidine and timolol maleate. The patient was diagnosed to
      have disseminated tuberculosis (tuberculoma of the brain) and was started with
      antituberculosis therapy. His condition improved significantly after the
      treatment, and keratitis in cornea started to clean up. 

PMID- 24577180
TI  - Posterior reversible encephalopathy syndrome (PRES) in a patient with late
      postpartum eclampsia.
AB  - Posterior reversible encephalopathy syndrome (PRES) is a reversible neurological
      entity characterised by seizure, headaches, visual symptoms, impaired
      consciousness and other focal neurological findings. It is caused by a wide
      variety of causes ultimately leading to a vasogenic cerebral oedema of occipital
      and parietal lobes of the brain. We present here a young woman with headache,
      generalised tonic-clonic seizures and cortical blindness in a late postpartum
      stage. Reversibility of the symptoms and characteristic imaging findings led us
      to a diagnosis of PRES in our patient. 

PMID- 24577181
TI  - alpha-Methyldopa-induced hepatitis during the postpartum period.
AB  - A 34-year-old woman, with a history of pre-eclampsia, was diagnosed with alpha
      methyldopa-induced hepatotoxicity, after she presented with severe jaundice and
      hepatitis 8 weeks following delivery. Laboratory investigations and liver biopsy
      ruled out other causes of hepatitis. She continued to improve clinically after
      cessation of alpha-methyldopa, and was discharged 10 days after admission. This
      case report emphasises that it may not be possible to predict which patients may
      develop alpha-methyldopa-induced hepatitis, hence regular monitoring of liver
      function tests during treatment should be implemented. 

PMID- 24577182
TI  - [Acute pancreatitis].
AB  - Acute pancreatitis is a potentially fatal disease with individually differing
      expression of systemic involvement. For this reason early diagnosis with
      subsequent risk stratification is essential in the clinical management of this
      frequent gastroenterological disorder. Severe forms of acute pancreatitis occur
      in approximately 20 % of cases often requiring intensive care monitoring and
      interdisciplinary therapeutic approaches. In the acute phase adequate fluid
      replacement and sufficient analgesic therapy is of major therapeutic importance.
      Concerning the administration of antibiotics and the nutritional support of
      patients with acute pancreatitis a change in paradigms could be observed in
      recent years. Furthermore, endoscopic, radiological or surgical interventions can
      be necessary depending on the severity of the disease and potential
      complications. 

PMID- 24577185
TI  - Chiral lanthanide complexes: coordination chemistry, spectroscopy, and catalysis.
AB  - The coordination chemistry and catalytic applications of organometallic and
      related lanthanide complexes bearing chiral oxazoline ligands is an area that has
      been largely underdeveloped, in comparison to complexes based upon lanthanide
      triflates for use in Lewis acid catalysis. In this article we report on the
      coordination chemistry of the bis(oxazolinylphenyl)amide (BOPA) ligand with
      lanthanide alkyl and amide co-ligands (Ln = Y, La, Pr, Nd, Sm). Their structural
      and spectroscopic characterisation are reported, including an assessment of their
      photophysical properties using luminescence spectroscopy, and are supported by
      density functional calculations. The application of these complexes in the
      hydroamination/cyclisation of aminoalkenes, and in the ring-opening
      polymerisation of rac-lactide is reported. 

PMID- 24577183
TI  - [Awake ECMO therapy in airway stenosis. Bronchoscopic treatment using laser
      resection].
AB  - This article presents the case of a 62-year-old patient with cancer in the left
      upper pulmonary lobe who underwent lobe resection with postoperative respiratory
      insufficiency. The right upper lobe had already been resected 5 years earlier
      because of an adenocarcinoma. Prior to the present surgery a computed tomography
      scan detected a narrow stenosis at the former resection site; however, both
      pulmonary lobes beyond this stenosis appeared to be sufficiently ventilated.
      After resection of the left upper lobe attempted extubation was unsuccessful due
      to insufficient global gas exchange as the stenosis prevented ventilation of the
      right lung. Bronchoscopy provided evidence of a normal diameter of the bronchus
      behind the stenosis so both lobes were to be recruited after possible correction
      of this section. A veno-venous extracorporeal membrane oxygenation device (ECMO)
      was established as bridging therapy to attain normal gas exchange. As the patient
      showed no muscle weakness and was cooperative, extubation was performed and
      spontaneous breathing occurred without any support while still under ECMO
      treatment. The stenosis was reduced by bronchoscopic laser resection within seven
      consecutive sessions. Each of these surgeries was conducted with the patient
      under general anesthesia with oral intubation and jet ventilation in combination
      with the ECMO. The patient was extubated after each treatment session and weaned
      from ECMO after the final resection within 2 days. This case demonstrates the use
      of ECMO in combination with surgical procedures in a spontaneously breathing
      patient as a causal therapy and option for selected patients to prevent
      complications from long-term ventilation. 

PMID- 24577186
TI  - Prognostic factors in 401 elderly women with metastatic breast cancer.
AB  - BACKGROUND: Elderly patients with metastatic breast cancer have a prognosis and
      outcome that may be dependent on a host of factors. PATIENTS AND METHODS: We
      retrospectively analyzed 401 female breast cancer patients who developed
      metastatic disease after the age of 70 years in order to define potential
      prognostic factors for specific survival at the time of first recurrence.
      RESULTS: With a median follow-up of 60 months from the time of recurrence, the
      median specific survival was 21.0 months (95% CI 17.0-23.0). In multivariate
      analysis we demonstrated that negative hormonal receptor status (p = 0.002),
      presence of positive lymph nodes at initial cancer diagnosis (hazard ratio, HR =
      1.37; 95% CI 1.07-1.75; p = 0.01), site of metastasis (p < 10(-4)) and metastasis
      free interval (HR = 0.99; 95% CI 0.95-0.99; p = 0.008) constituted unfavorable
      independent prognostic factors able to predict specific survival from the time of
      metastatic occurrence. Age at initial diagnosis, Scarff-Bloom Richardson grade
      and adjuvant treatments were significant only in univariate analysis. CONCLUSION:
      These survival prognostic factors associated with the use of a specific geriatric
      questionnaire to assess frailty may assist physicians in evaluating the patient's
      survival potential and choose a tailored treatment to this cancer population.

PMID- 24577187
TI  - Assessing the costs and effects of antiretroviral therapy task shifting from
      physicians to other health professionals in ethiopia.
AB  - OBJECTIVE: To evaluate the effects, costs, and cost-effectiveness of different
      degrees of antiretroviral therapy task shifting from physician to other health
      professionals in Ethiopia. DESIGN: Two-year retrospective cohort analysis on
      antiretroviral therapy patients coupled with cost analysis. INTERVENTIONS:
      Facilities with minimal or moderate task shifting compared with facilities with
      maximal task shifting. Maximal task shifting is defined as nonphysician
      clinicians handling both severe drug reactions and antiretroviral drug regimen
      changes. Secondary analysis compares health centers to hospitals. MAIN OUTCOME
      MEASURES: The primary effectiveness measure is the probability of a patient
      remaining actively on antiretroviral therapy for 2 years; the cost measure is the
      cost per patient per year. RESULTS: All facilities had some task shifting. About
      89% of patients were actively on treatment 2 years after antiretroviral treatment
      (ART) initiation, with no statistically significant differences between
      facilities with maximal and minimal or moderate task shifting. It cost about $206
      per patient per year for ART, with no statistically significant difference
      between the comparison groups. The cost-effectiveness of maximal task shifting is
      similar to minimal or moderate task shifting, with the same results obtained
      using regression to control for facility characteristics. CONCLUSIONS: Shifting
      the handling of both severe drug reactions and antiretroviral drug regimen
      changes from physicians to other clinical officers is not associated with a
      significant change in the 2-year treatment success rate or the costs of ART care.
      As an observational study, these results are tentative, and more research is
      needed in determining the optimal patterns of task shifting.

PMID- 24577188
TI  - World Health Organization's stage 4 conditions among adults accessing outpatient
      HIV care: a retrospective cohort study in Kisumu, Kenya.

PMID- 24577189
TI  - Plasma lipopolysaccharide and triglycerides are independently associated and both
      markers correlate with the development of metabolic syndrome in HIV infection.

PMID- 24577190
TI  - A 'hidden' 18O-enriched reservoir in the sub-arc mantle.
AB  - Plate subduction continuously transports crustal materials with high-delta(18)O
      values down to the mantle wedge, where mantle peridotites are expected to achieve
      the high-delta(18)O features. Elevated delta(18)O values relative to the upper
      mantle value have been reported for magmas from some subduction zones. However,
      peridotites with delta(18)O values significantly higher than the well-defined
      upper mantle values have never been observed from modern subduction zones. Here
      we present in-situ oxygen isotope data of olivine crystals in Sailipu mantle
      xenoliths from South Tibet, which have been subjected to a long history of
      Tethyan subduction before the India-Asia collision. Our data identify for the
      first time a metasomatized mantle that, interpreted as the sub-arc lithospheric
      mantle, shows anomalously enriched oxygen isotopes (delta(18)O = +8.03 +/- 0.28
      0/00). Such a high-delta(18)O mantle commonly does not contribute significantly
      to typical island arc basalts. However, partial melting or contamination of such
      a high-delta(18)O mantle is feasible to account for the high-delta(18)O
      signatures in arc basalts. 

PMID- 24577192
TI  - Evaluation of color spatio-temporal interest points for human action recognition.
AB  - This paper considers the recognition of realistic human actions in videos based
      on spatio-temporal interest points (STIPs). Existing STIP-based action
      recognition approaches operate on intensity representations of the image data.
      Because of this, these approaches are sensitive to disturbing photometric
      phenomena, such as shadows and highlights. In addition, valuable information is
      neglected by discarding chromaticity from the photometric representation. These
      issues are addressed by color STIPs. Color STIPs are multichannel reformulations
      of STIP detectors and descriptors, for which we consider a number of chromatic
      and invariant representations derived from the opponent color space. Color STIPs
      are shown to outperform their intensity-based counterparts on the challenging UCF
      sports, UCF11 and UCF50 action recognition benchmarks by more than 5% on average,
      where most of the gain is due to the multichannel descriptors. In addition, the
      results show that color STIPs are currently the single best low-level feature
      choice for STIP-based approaches to human action recognition.

PMID- 24577193
TI  - Analysis and exploitation of multipath ghosts in radar target image
      classification.
AB  - An analysis of the relationship between multipath ghosts and the direct target
      image for radar imaging is presented. A multipath point spread function (PSF) is
      defined that allows for specular reflections in the local environment and can
      allow the ghost images to be localized. Analysis of the multipath PSF shows that
      certain ghosts can only be focused for the far field synthetic aperture radar
      case and not the full array case. Importantly, the ghosts are shown to be
      equivalent to direct target images taken from different observation angles. This
      equivalence suggests that exploiting the ghosts would improve target
      classification performance, and this improvement is demonstrated using
      experimental data and a naive Bayesian classifer. The maximum performance gain
      achieved is 32%.

PMID- 24577191
TI  - Correlation dynamics and enhanced signals for the identification of serial
      biomolecules and DNA bases.
AB  - Nanopore-based sequencing has demonstrated a significant potential for the
      development of fast, accurate, and cost-efficient fingerprinting techniques for
      next generation molecular detection and sequencing. We propose a specific
      multilayered graphene-based nanopore device architecture for the recognition of
      single biomolecules. Molecular detection and analysis can be accomplished through
      the detection of transverse currents as the molecule or DNA base translocates
      through the nanopore. To increase the overall signal-to-noise ratio and the
      accuracy, we implement a new 'multi-point cross-correlation' technique for
      identification of DNA bases or other molecules on the single molecular level. We
      demonstrate that the cross-correlations between each nanopore will greatly
      enhance the transverse current signal for each molecule. We implement first
      principles transport calculations for DNA bases surveyed across a multilayered
      graphene nanopore system to illustrate the advantages of the proposed geometry. A
      time-series analysis of the cross-correlation functions illustrates the potential
      of this method for enhancing the signal-to-noise ratio. This work constitutes a
      significant step forward in facilitating fingerprinting of single biomolecules
      using solid state technology. 

PMID- 24577194
TI  - Manifold learning for object tracking with multiple nonlinear models.
AB  - This paper presents a novel manifold learning algorithm for high-dimensional data
      sets. The scope of the application focuses on the problem of motion tracking in
      video sequences. The framework presented is twofold. First, it is assumed that
      the samples are time ordered, providing valuable information that is not
      presented in the current methodologies. Second, the manifold topology comprises
      multiple charts, which contrasts to the most current methods that assume one
      single chart, being overly restrictive. The proposed algorithm, Gaussian process
      multiple local models (GP-MLM), can deal with arbitrary manifold topology by
      decomposing the manifold into multiple local models that are probabilistic
      combined using Gaussian process regression. In addition, the paper presents a
      multiple filter architecture where standard filtering techniques are integrated
      within the GP-MLM. The proposed approach exhibits comparable performance of state
      of-the-art trackers, namely multiple model data association and deep belief
      networks, and compares favorably with Gaussian process latent variable models.
      Extensive experiments are presented using real video data, including a publicly
      available database of lip sequences and left ventricle ultrasound images, in
      which the GP-MLM achieves state of the art results.

PMID- 24577195
TI  - Contextual hashing for large-scale image search.
AB  - With the explosive growth of the multimedia data on the Web, content-based image
      search has attracted considerable attentions in the multimedia and the computer
      vision community. The most popular approach is based on the bag-of-visual-words
      model with invariant local features. Since the spatial context information among
      local features is critical for visual content identification, many methods
      exploit the geometric clues of local features, including the location, the scale,
      and the orientation, for explicitly post-geometric verification. However, usually
      only a few initially top-ranked results are geometrically verified, considering
      the high computational cost in full geometric verification. In this paper, we
      propose to represent the spatial context of local features into binary codes, and
      implicitly achieve geometric verification by efficient comparison of the binary
      codes. Besides, we explore the multimode property of local features to further
      boost the retrieval performance. Experiments on holidays, Paris, and Oxford
      building benchmark data sets demonstrate the effectiveness of the proposed
      algorithm.

PMID- 24577196
TI  - Spatiotemporal grid flow for video retargeting.
AB  - Video retargeting is a useful technique to adapt a video to a desired display
      resolution. It aims to preserve the information contained in the original video
      and the shapes of salient objects while maintaining the temporal coherence of
      contents in the video. Existing video retargeting schemes achieve temporal
      coherence via constraining each region/pixel to be deformed consistently with its
      corresponding region/pixel in neighboring frames. However, these methods often
      distort the shapes of salient objects, since they do not ensure the content
      consistency for regions/pixels constrained to be coherently deformed along time
      axis. In this paper, we propose a video retargeting scheme to simultaneously meet
      the two requirements. Our method first segments a video clip into spatiotemporal
      grids called grid flows, where the consistency of the content associated with a
      grid flow is maintained while retargeting the grid flow. After that, due to the
      coarse granularity of grid, there still may exist content inconsistency in some
      grid flows. We exploit the temporal redundancy in a grid flow to avoid that the
      grids with inconsistent content be incorrectly constrained to be coherently
      deformed. In particular, we use grid flows to select a set of key-frames which
      summarize a video clip, and resize subgrid-flows in these key-frames. We then
      resize the remaining nonkey-frames by simply interpolating their grid contents
      from the two nearest retargeted key-frames. With the key-frame-based scheme, we
      only need to solve a small-scale quadratic programming problem to resize subgrid
      flows and perform grid interpolation, leading to low computation and memory
      costs. The experimental results demonstrate the superior performance of our
      scheme.

PMID- 24577197
TI  - The importance of amyloid beta protein in cerebrospinal fluid when you recognize
      convexal subarachnoid hemorrhage.
AB  - BACKGROUND: Convexal subarachnoid hemorrhage (cSAH) is sometimes experienced in
      cerebral amyloid angiopathy (CAA), but ones that are repeated within a brief time
      period are not common. Also, it is often difficult to diagnose CAA when you
      experience a case of cSAH. METHODS: We examined the clinical course of 2 cases
      that showed cSAH repeatedly. We examined cerebrospinal fluid (CSF) concentrations
      of amyloid beta protein (Abeta) 40 and 42 and tau protein as additional evidence
      for a diagnosis of CAA. RESULTS: Case 1 presented with transient motor paresis of
      the left hand and case 2 with transient sensory disturbance of the left hand. CT
      scans showed cSAH on the right central sulcus in both patients. Case 1 showed
      development of intracerebral hemorrhage on the frontal lobe near the right
      central sulcus. Case 2 showed relapse of cSAH with recurrence of the same
      symptoms. These cases could not be diagnosed by image analysis, but were
      considered CAA by Abeta40, Abeta42 and tau protein in CSF. CONCLUSION: Abeta in
      CSF can be presented here as support for the diagnosis of CAA that is difficult
      to diagnose by Boston criteria.

PMID- 24577198
TI  - Hormone-independent pathways of sexual differentiation.
AB  - New observations over the last 25 years of hormone-independent sexual dimorphisms
      have gradually and unequivocally overturned the dogma, arising from Jost's
      elegant experiments in the mid-1900s, that all somatic sex dimorphisms in
      vertebrates arise from the action of gonadal hormones. Although we know that Sry,
      a Y-linked gene, is the primary gonadal sex determinant in mammals, more recent
      analysis in marsupials, mice, and finches has highlighted numerous sexual
      dimorphisms that are evident well before the differentiation of the testis and
      which cannot be explained by a sexually dimorphic hormonal environment. In
      marsupials, scrotal bulges and mammary primordia are visible before the testis
      has differentiated due to the expression of a gene(s) on the X chromosome. ZZ and
      ZW gynandromorph finches have brains that develop in a sexually dimorphic way
      dependent on their sex chromosome content. In genetically manipulated mice, it is
      the X chromosomes, not the gonads, that determine many characters including rate
      of early development, adiposity, and neural circuits. Even spotted hyenas have
      sexual dimorphisms that cannot be simply explained by hormonal exposure. This
      review discusses the recent findings that confirm that there are hormone
      independent sexual dimorphisms well before the gonads begin to produce their
      hormones.

PMID- 24577200
TI  - Serum fibroblast growth factor 23 is a useful marker to distinguish vitamin D
      deficient rickets from hypophosphatemic rickets.
AB  - BACKGROUND/AIMS: Vitamin D-deficient rickets (DR) has recently re-emerged among
      developed countries. Vitamin D deficiency can influence biochemical results of
      patients with fibroblast growth factor 23 (FGF23)-related hereditary
      hypophosphatemic rickets (HR), making differential diagnosis difficult. In the
      present study we evaluated the utility of serum FGF23 levels in the diagnosis of
      DR and during its treatment. METHODS: The study group comprised 24 children with
      DR and 8 children with HR. Serum FGF23 levels and bone metabolism-related
      measurements were assessed. RESULTS: Serum FGF23 levels in patients with DR were
      less than 19 pg/ml, while those in patients with HR were more than 57 pg/ml.
      There were significant differences in serum levels of calcium, phosphate,
      parathyroid hormone, and 1,25-dihydroxyvitamin D, as well as tubular maximum
      phosphate reabsorption per glomerular filtration rate between patients with DR
      and HR, but these values were not fully mutually exclusive. In addition, serum
      FGF23 and phosphate levels were increased following treatment. CONCLUSION: Serum
      FGF23 level is the most critical biochemical marker for distinguishing DR from HR
      and might be a good indicator of biochemical response to the intervention. Serum
      FGF23 levels show utility for the diagnosis of DR and in the assessment of its
      response to treatment.

PMID- 24577201
TI  - OBESITY FACTS - a retrospective and the way forward.

PMID- 24577199
TI  - Species-dependent neuropathology in transgenic SOD1 pigs.
AB  - Mutations in the human copper/zinc superoxide dismutase 1 (hSOD1) gene cause
      familial amyotrophic lateral sclerosis (ALS). It remains unknown whether large
      animal models of ALS mimic more pathological events seen in ALS patients via
      novel mechanisms. Here, we report the generation of transgenic pigs expressing
      mutant G93A hSOD1 and showing hind limb motor defects, which are germline
      transmissible, and motor neuron degeneration in dose- and age-dependent manners.
      Importantly, in the early disease stage, mutant hSOD1 did not form cytoplasmic
      inclusions, but showed nuclear accumulation and ubiquitinated nuclear aggregates,
      as seen in some ALS patient brains, but not in transgenic ALS mouse models. Our
      findings revealed that SOD1 binds PCBP1, a nuclear poly(rC) binding protein, in
      pig brain, but not in mouse brain, suggesting that the SOD1-PCBP1 interaction
      accounts for nuclear SOD1 accumulation and that species-specific targets are key
      to ALS pathology in large mammals and in humans. 

PMID- 24577203
TI  - [Anatomy and pathogenesis of diverticular disease].
AB  - BACKGROUND: Although diverticular disease is one of the most frequent
      gastrointestinal disorders the pathogenesis is not yet sufficiently clarified.
      OBJECTIVES: The aim is to define the anatomy and pathogenesis of diverticular
      disease considering the risk factors and description of structural and functional
      alterations of the bowel wall. METHODS: This article gives an appraisal of the
      literature, presentation and evaluation of classical etiological factors,
      analysis and discussion of novel pathogenetic concepts. RESULTS: Colonic
      diverticulosis is defined as an acquired out-pouching of multiple and initially
      asymptomatic pseudodiverticula through muscular gaps in the colon wall.
      Diverticular disease is characterized by diverticular bleeding and/or
      inflammatory processes (diverticulitis) with corresponding complications (e.g.
      abscess formation, fistula, covered and open perforation, peritonitis and
      stenosis). Risk factors for diverticular disease include increasing age, genetic
      predisposition, congenital connective tissue diseases, low fiber diet, high meat
      consumption and pronounced overweight. Alterations of connective tissue cause a
      weakening of preformed exit sites of diverticula and rigidity of the bowel wall
      with reduced flexibility. It is assumed that intestinal innervation disorders and
      structural alterations of the musculature induce abnormal contractile patterns
      with increased intraluminal pressure, thereby promoting the development of
      diverticula. Moreover, an increased release of pain-mediating neurotransmitters
      is considered to be responsible for persistent pain in chronic diverticular
      disease. CONCLUSIONS: According to the present data the pathogenesis of
      diverticular disease cannot be attributed to a single factor but should be
      considered as a multifactorial event.

PMID- 24577204
TI  - The role of cerebellar volume in cognition in the general elderly population.
AB  - BACKGROUND: It is unknown whether the cerebellum affects cognitive function in an
      aging community-dwelling population. In a population-based study on 3745
      nondemented individuals aged 45 years and above, we investigated the relationship
      between cerebellar volume and cognitive function. METHODS: Brain volumes were
      obtained using automatic tissue segmentation of magnetic resonance imaging scans.
      Cognitive functioning was assessed using MMSE and cognitive compound scores of
      global cognition, executive function, information processing speed, memory, and
      motor speed. Linear regression modeling was used to study the associations
      between cerebellar volumes and cognitive measures, independent of cerebral
      volumes. RESULTS: We found a relationship between larger cerebellar volume and
      better global cognition, executive function, information processing speed, and
      motor speed. After adjustment for cerebral volume, only cerebellar gray matter
      volume remained borderline significantly associated with global cognition and
      information processing speed. After Bonferroni correction, the few associations
      found between cerebellar volume and cognition disappeared. CONCLUSIONS: We only
      found a minor relationship between larger cerebellar volume and better cognition
      in healthy older adults, which further attenuated after correcting for cerebral
      volume. Our findings support the notion that cerebellar volume has an influence
      on cognition in aging, but that it is not the major leading structure.

PMID- 24577208
TI  - Does patient autonomy extend to ending life?

PMID- 24577205
TI  - Social relationships and risk of incident mild cognitive impairment in U.S.
      Alzheimer's disease centers.
AB  - Social relationships are hypothesized to prevent or slow cognitive decline. We
      sought to evaluate associations between social relationships and mild cognitive
      impairment (MCI). Participants from the National Alzheimer's Coordinating Center
      database who were cognitively normal, aged 55 and older at baseline, and had at
      least 2 in-person visits (n=5335) were included. Multivariable Cox proportional
      hazard models evaluated the association between 4 social relationships at
      baseline (marital status, living situation, having children, and having siblings)
      and risk of developing MCI (on the basis of clinician diagnosis following
      established criteria). Primary models were adjusted for baseline demographics.
      Participants were followed, on average, for 3.2 years; 15.2% were diagnosed with
      MCI. Compared with married participants, risk of MCI was significantly lower for
      widowed participants (hazard ratio: 0.87; 95% confidence interval: 0.76, 0.99)
      but not for divorced/separated or never-married participants. Compared with
      living with a spouse/partner, risk of MCI was significantly higher for living
      with others (hazard ratio: 1.35; 95% confidence interval: 1.03, 1.77) but not for
      living alone. Risk of MCI was not associated with having children or having
      siblings. These results did not consistently identify social relationships as a
      strong risk factor for, or independent clinical predictor of, MCI. 

PMID- 24577209
TI  - The use of syringe drivers in the community: considerations for palliative care
      providers.
AB  - 'Caring for him at home was such a sad, challenging but rewarding and special
      time ... we wouldn't have wanted him to die anywhere else ... things improved
      after the syringe driver was started as he seemed more at ease and was not
      suffering anymore ... the twinkle returned to his eyes for a while ... it made
      such a positive difference and allowed us to carry on at home until the end.'
      These words from the family of a dying patient recently cared for by the author
      remind us of how special the care given at the end of life is. 

PMID- 24577210
TI  - Supporting care integration with Electronic Palliative Care Coordination Systems
      (EPaCCS).

PMID- 24577211
TI  - Quality of end-of-life care for those who die at home: views and experiences of
      bereaved relatives and carers.
AB  - Little is known about the quality of the end-of-life care patients receive at
      home. This paper reports findings from a study that explored bereaved relatives'
      and carers' experiences of end-of-life care at home using the Care of the Dying
      Evaluation (CODE) questionnaire. Narrative data from questionnaires completed by
      72 carers of patients who had died at home in the North West of England underwent
      qualitative analysis. In general good quality care was provided, but there were
      times when adequate support was not evident in relation to pain control and what
      to expect when death was imminent. The study provides useful information for
      those who provide end-of-life care at home. 

PMID- 24577206
TI  - Repeated Delta9-tetrahydrocannabinol exposure in adolescent monkeys: persistent
      effects selective for spatial working memory.
AB  - OBJECTIVE: Epidemiological findings suggest that, relative to adults, adolescents
      are more vulnerable to the adverse persistent effects of cannabis on working
      memory. However, the potential confounds inherent in human studies preclude
      direct determination of a cause-and-effect relationship between adolescent
      cannabis use and heightened susceptibility to persistent working memory
      impairments. Consequently, the authors examined the effects of repeated exposure
      to Delta9-tetrahydrocannabinol (THC) on performance of spatial and object working
      memory tasks in adolescent monkeys. METHOD: Seven pairs of male adolescent rhesus
      monkeys, matched for baseline cognitive performance, received vehicle or THC
      intravenously 5 days/week for 6 months. Performance on spatial and object memory
      tasks was assessed 23 or 71 hours after drug administration throughout the study.
      In addition, acute effects on working memory were also assessed at the beginning
      and end of the 6-month period. RESULTS: Relative to the vehicle-exposed control
      animals, those with repeated THC exposure had a blunted trajectory of accuracy
      improvements on the spatial working memory task in a delay-dependent manner.
      Accuracy improvements on the object working memory task did not differ between
      groups. Relative to the acute effects of THC on working memory at the beginning
      of the study, neither sensitivity nor tolerance was evident after 6 months of THC
      exposure. CONCLUSIONS: Because maturation of performance is later for spatial
      than for object working memory, these findings suggest that persistent effects of
      THC on cognitive abilities are more evident when exposure coincides with the
      developmental stage during which the underlying neural circuits are actively
      maturing.

PMID- 24577212
TI  - Iranian nurses' perceptions of palliative care for patients with cancer pain.
AB  - AIM: The purpose of this study was to identify Iranian nurses' perceptions of
      palliative care for patients with cancer pain. METHODS: The study took a
      qualitative approach. Semi-structured interviews were held with 15 nurses with
      Bachelor's degrees working in three teaching hospitals in Iran. Transcripts of
      the interviews underwent content analysis, and categories were extracted from the
      material. FINDINGS: The findings came under two main categories: management of
      physical pain and psychological empowerment. Management of physical pain had two
      subcategories: the importance of communication, and pain palliation using drugs.
      Psychological empowerment also had two subcategories: supportive behaviour and
      distress reduction. CONCLUSION: The sample felt that palliative care for patients
      with cancer pain must include psychological empowerment, support, and
      communication as well as physical pain relief.

PMID- 24577213
TI  - An overview of hospice and palliative care nursing models and theories.
AB  - Current literature reports that nurses are the members of the health-care team
      who have the most contact with patients facing a life-threatening illness. The
      multidisciplinary palliative care approach means that hospice and palliative care
      nurses require a consistent theoretical foundation in order to be confident of
      and able to explain their role. The aim of this paper is to describe existing
      palliative care and hospice nursing models and theories and to identify their
      core concepts. Literature published between 2002 and 2012 on such models was
      reviewed and subjected to content analysis. Ten core concepts were identified
      that fell into three categories: patient, nurse, and therapeutic relationship.
      The themes and values identified in the end-of-life nursing models and theories
      are congruent with palliative care best practices based on a patient-centred and
      an interdisciplinary teamwork approach. In developing a therapeutic relationship
      with patients, nurses have a 'privileged' experience that may lead to existential
      growth and job satisfaction. 

PMID- 24577214
TI  - Reaching out to Ray: delivering palliative care services to a homeless person in
      Melbourne, Australia.
AB  - Most terminally ill people express a preference for dying at home. Within
      established models of palliative care, achieving death at home is a particular
      challenge for homeless people. This paper describes a quality-improvement project
      undertaken by a community-based palliative care service in Melbourne, Australia,
      to understand homeless people's palliative care needs and the challenges that
      workers face. Six semi-structured interviews with workers in hospital and
      community-based settings were undertaken and a case study documented. The results
      were used to initiate discussion about how policy and protocols for the community
      based palliative care service might serve this population more effectively. The
      findings confirmed that homeless people have complex psychosocial and medical
      needs. They may be periodically uncontactable or living in unsafe settings,
      experience isolation from social support networks, and have issues of compliance
      with treatment protocols exacerbated by mental health problems and/or substance
      abuse. Service providers had particular challenges in meeting the palliative care
      needs of homeless people. A flexible, compassionate, and coordinated response is
      required, and more work is needed to explore how the needs of this particular
      group can be met. 

PMID- 24577215
TI  - Findings from a nursing scholarship study tour to inform a proposal for a day
      hospice model in South Australia.
AB  - South Australia releases national and international travel scholarships every
      year to the nursing and midwifery workforce to enable them to undertake
      observational site visits to inform the development of service models that can be
      introduced into care practices back in South Australia. Ten sites across New
      Zealand, Canada, and the UK agreed to host a site visit as part of a scholarship
      to look at day hospice (DH) programmes. The author undertook an observational
      study that included participation in DH programmes and discussions with staff and
      patients. There were many similarities across the three countries, in particular
      in the structure of the programmes, the staff makeup, and the support of the
      volunteer workforce. Two distinct models were observed: social and medical. Each
      has its value and both need to be incorporated to ensure services and
      participants have their needs met. Based on the site visits and other research,
      the author devised a proposal for South Australia to commence with a time-limited
      sessional group DH programme with a focus on maintenance of function for
      participants coupled with caregiver education and information provision. 

PMID- 24577216
TI  - We are marching in.

PMID- 24577219
TI  - Improving mechanical fatigue resistance by optimizing the nanoporous structure of
      inkjet-printed Ag electrodes for flexible devices.
AB  - The development of highly conductive metallic electrodes with long-term
      reliability is in great demand for real industrialization of flexible
      electronics, which undergo repeated mechanical deformation during service. In the
      case of vacuum-deposited metallic electrodes, adequate conductivity is provided,
      but it degrades gradually during cyclic mechanical deformation. Here, we
      demonstrate a long-term reliable Ag electrode by inkjet printing. The electrical
      conductivity and the mechanical reliability during cyclic bending are
      investigated with respect to the nanoporous microstructure caused by post heat
      treatment, and are compared to those of evaporated Ag films of the same
      thickness. It is shown that there is an optimized nanoporous microstructure for
      inkjet-printed Ag films, which provides a high conductivity and improved
      reliability. It is argued that the nanoporous microstructure ensures connectivity
      within the particle network and at the same time reduces plastic deformation and
      the formation of fatigue damage. This concept provides a new guideline to develop
      an efficient method for highly conductive and reliable metallic electrodes for
      flexible electronics. 

PMID- 24577220
TI  - High-harmonic generation and parametric amplification in the soft X-rays from
      extended electron trajectories.
AB  - We report, for the first time, the generation of high-order harmonics in a
      spectral range between 200 eV and 1 keV with an unusual spectral property: only
      every 4(th) (4i + 1, i??) harmonic line appears, whereas the usual high-harmonic
      spectra consist of every odd (2i + 1) harmonic. We attribute this unique property
      to the quantum path interference of two extended electron trajectories that
      experience multiple re-scattering. In the well-established theory, electrons
      emitted via tunnel ionisation are accelerated by a laser field, return to the ion
      and recombine. The acceleration typically lasts for less than one optical cycle,
      and the electrons radiate in the extreme ultraviolet range at recombination. In
      contrast, for extended trajectories, electrons are accelerated over two or more
      optical cycles. Here, we demonstrate that two sets of trajectories dominate and
      provide substantial contributions to the generated soft X-ray radiation because
      they fulfil the resonance condition for X-ray parametric amplification.

PMID- 24577221
TI  - Vascular aphasia outcome after intravenous recombinant tissue plasminogen
      activator thrombolysis for ischemic stroke.
AB  - INTRODUCTION: No data about the specific outcome of aphasia after thrombolysis
      are available. Our aim was to describe the severity and type of aphasia after
      stroke thrombolysis. METHODS: This retrospective cohort study included
      consecutive aphasic patients hospitalized in the Stroke Unit of Dijon (University
      Hospital, France) between 2004 and 2009 for a first-ever ischemic stroke of the
      left middle cerebral artery. Aphasic syndromes and their severity (French version
      of the Boston Diagnostic Aphasia Examination) were evaluated during the first
      week and 3 months after stroke. RESULTS: In multivariate analyses, the severity
      of aphasia in the 37 thrombolysed patients was milder than in the 38
      nonthrombolysed patients during the first week (adjusted OR = 10.13, 95% CI: 2.43
      42.28, p = 0.002) and at 3 months (adjusted OR = 8.44, 95% CI: 2.76-25.80, p =
      0.001). The frequency of mild aphasia (conduction or atypical) was not
      significantly higher in thrombolysed patients during the first week after stroke
      (adjusted OR = 5.80, 95% CI: 0.82-41.16, p = 0.079). CONCLUSION: The severity of
      aphasia during the first week and 3 months after stroke is milder in thrombolysed
      than in nonthrombolysed patients, perhaps because of a greater frequency of
      conduction and mild atypical aphasia.

PMID- 24577223
TI  - Solvents and auxiliary ligands co-regulate three antiferromagnetic Co(II) MOFs
      based on a semi-rigid carboxylate ligand.
AB  - By reacting an asymmetry semi-rigid Y-shaped/L-shaped linker H3cpta (H3cpta = 3
      (4'-carboxyphenoxy)phthalic acid) and Co(CH3COO)2.6H2O under different N-donor
      ligands in different solvents, three new Co-based coordination polymers,
      [Co3(cpta)2(bpe)3(H2O)4] (1) [Co(MU2-H2O)(MU3-OH)(Hcpta)(bpe)(H2O).3(DMF)3(H2O)]
      (2) and [Co3(cpta)2(bpa)4] (3) have been obtained. They exhibit trinodal
      topological nets/layer, based on Co(2+) ions and Y-shaped/L-shaped carboxylate
      linkers. 1 and 3 present 3D frameworks with the point symbol
      {4.10(2)}2{10(5).12}{4.8(5)}2 for 1 and {4.8(2)}2{8(5).9}{4.6(7).9(2)}2 for 3.
      While, 2 exhibits a 2D layer with the point symbol {4.6.8}{4.6(2).8(3)}{6(2).8}.
      The magnetic studies indicate that all of the three complexes show
      antiferromagnetic exchanges transmitted through MU3-carboxylate/MU4-carboxylate
      bridges, MU2-H2O molecules and MU3-OH ions between Co(2+) ions, respectively. And
      the result of this research shows that the solvent and the secondary ligands
      could co-regulate coordination polymer with interesting properties, providing a
      constructive guidance when synthesizing versatile topologies with the same
      organic spacer but a different architecture. 

PMID- 24577222
TI  - Indoor tanning among high school students in the United States, 2009 and 2011.
AB  - IMPORTANCE: Indoor tanning is associated with an increased risk of skin cancer,
      including melanoma, and is particularly dangerous for younger and more frequent
      indoor tanners. OBJECTIVE: To examine the prevalence of indoor tanning and
      frequent indoor tanning (>=10 times during the 12 months before each survey) and
      their association with health-related behaviors. DESIGN, SETTING, AND
      PARTICIPANTS: A cross-sectional study examined data from the 2009 and 2011
      national Youth Risk Behavior Surveys, which used nationally representative
      samples of US high school students representing approximately 15.5 million
      students each survey year. The study included 25,861 students who answered the
      indoor tanning question. MAIN OUTCOMES AND MEASURES: The prevalence of indoor
      tanning and frequent indoor tanning were examined as well as their association
      with demographic characteristics and health-related behaviors using multivariable
      logistic regression modeling. RESULTS: The prevalence of indoor tanning was
      greater among female, older, and non-Hispanic white students. Indoor tanning was
      highest among female students aged 18 years or older, with 31.5% engaging in
      indoor tanning in 2011, and among non-Hispanic white female students, with 29.3%
      engaging in indoor tanning in 2011. Among female students, the adjusted
      prevalence of indoor tanning decreased from 26.4% in 2009 to 20.7% in 2011. Among
      female and male students, indoor tanning was associated with other risk-taking
      behaviors, such as binge drinking (P < .001 and P = .006, respectively),
      unhealthy weight control practices (P < .001, for both), and having sexual
      intercourse (P < .001, for both). Additionally, indoor tanning among female
      students was associated with using illegal drugs (P < .001) and having sexual
      intercourse with 4 or more persons (P = .03); use among male students was
      associated with taking steroids without a physician's prescription (P < .001),
      smoking cigarettes daily (P = .03), and attempting suicide (P = .006). More than
      half of respondents engaging in indoor tanning reported frequent use of the
      devices. CONCLUSIONS AND RELEVANCE: Indoor tanning is common among high school
      students. Public health efforts are needed to change social norms regarding
      tanned skin and to increase awareness, knowledge, and behaviors related to indoor
      tanning. The clustering of risky behaviors suggests a need for coordinated,
      multifaceted approaches, including primary care physician counseling, to address
      such behaviors among adolescents.

PMID- 24577224
TI  - Decreased CALM expression reduces Abeta42 to total Abeta ratio through clathrin
      mediated endocytosis of gamma-secretase.
AB  - A body of evidence suggests that aberrant metabolism of amyloid-beta peptide
      (Abeta) underlies the aetiology of Alzheimer disease (AD). Recently, a single
      nucleotide polymorphism in phosphatidylinositol binding clathrin assembly protein
      (PICALM/CALM) gene, which encodes a protein implicated in the clathrin-mediated
      endocytosis, was identified as a genetic protective factor for AD, although its
      mechanistic details have little been explored. Here we show that loss of CALM
      leads to the selective decrease in the production ratio of the pathogenic Abeta
      species, Abeta42. Active form of gamma-secretase is constitutively endocytosed
      via the clathrin-mediated pathway in a CALM dependent manner. Alteration in the
      rate of clathrin-mediated endocytosis of gamma-secretase causes a shift in its
      steady-state localization, which consequently impacts on the production ratio of
      Abeta42. Our study identifies CALM as an endogenous modulator of gamma-secretase
      activity by regulating its endocytosis and also as an excellent target for
      Abeta42-lowering AD therapeutics. 

PMID- 24577225
TI  - N-Heterocyclic carbene-catalyzed formal cross-coupling reaction of alpha
      haloenals with thiols: organocatalytic construction of sp2 carbon-sulfur bonds.
AB  - A novel N-heterocyclic carbene (NHC)-catalyzed formal cross-coupling reaction
      between alpha-haloenals and thiols was developed. In the presence of 5 mol% NHC
      precursors and 1.6 equiv. potassium carbonate, various thiols coupled with alpha
      haloenals to produce alpha-thioenals in 53% to 91% yield and excellent Z
      selectivity. 

PMID- 24577226
TI  - Main congenital cerebral anomalies: how prenatal imaging aids counseling.
AB  - The purpose of this article is to discuss some common cerebral lesions that may
      be detected during prenatal screening: corpus callosum dysgenesis, absent septum
      pellucidum, localized parenchymal ischemic-hemorrhagic lesions, megacisterna
      magna, Blake's pouch cyst, posterior fossa arachnoid cyst and Dandy-Walker
      malformation. For each cerebral defect, the main imaging findings are reminded,
      certain differential diagnoses are discussed and prenatal diagnostic accuracy is
      analyzed with emphasis on uncertainties encountered during analysis of ultrasound
      or magnetic resonance images. Detecting cerebral lesions in fetuses requires
      rapid counseling by neuropediatricians. Keeping in mind that the prenatal
      diagnostic accuracy is not 100%, the neuropediatricians have to answer the
      parents' questions regarding the outcome of the unborn child as well as the risk
      of recurrence for future pregnancies. This article is based on the authors' large
      experience in both prenatal imaging and neurocounseling. The frequently asked
      questions are set up. Answers are provided, underscoring the importance of an
      appropriate description of the cerebral defect, and therefore the pivotal role of
      prenatal imaging. However, prenatal neurocounseling remains challenging and the
      parents must be aware of uncertainties regarding both diagnostic accuracy and
      prognostic evaluation.

PMID- 24577227
TI  - Vacuum-assisted closure device as a split-thickness skin graft bolster in the
      burn population.
AB  - The vacuum-assisted closure device (VAC) is associated with improved wound
      healing outcomes. Its use as a bolster device to secure a split-thickness skin
      graft has been previously demonstrated; however, there is little published
      evidence demonstrating its benefits specifically in the burn population. With use
      of the VAC becoming more commonplace, its effect on skin graft take and overall
      time to healing in burn patients deserves further investigation. Retrospective
      review of burn registry database at a high-volume level I trauma center and
      regional burn center during a 16-month period was performed. Patients who had a
      third-degree burn injury requiring a split-thickness skin graft and who received
      a VAC bolster were included. Data points included age, sex, burn mechanism, burn
      location, grafted area in square centimeters, need for repeat grafting, percent
      graft take, and time to complete reepithelialization. Sixty-seven patients were
      included in the study with a total of 88 skin graft sites secured with a VAC. Age
      ranged from <1 year to 84 years (average 41 years). The average grafted area was
      367 +/- 545 cm. The three most common were the leg, thigh, and arm (28, 15, and
      12%, respectively). Average percent graft take was 99.5 +/- 1.5%. Notably, no
      patients returned to the operating room for repeat grafting. The average time to
      complete reepithelialization was 16 +/- 7 days. The VAC is a highly reliable and
      reproducible method to bolster a split-thickness skin graft in the burn
      population. The observed rate of zero returns to the operating room for repeat
      grafting was especially encouraging. Its ability to conform to contours of the
      body and cover large surface areas makes it especially useful in securing a
      graft. This method of bolstering results in decreased repeat grafting and minimal
      graft loss, thus decreasing morbidity compared with conventional bolster
      dressings. 

PMID- 24577228
TI  - Is non-alcoholic fatty liver disease less frequent among women with Prader-Willi
      syndrome?
AB  - OBJECTIVE: Patients with Prader-Willi syndrome (PWS) have been hypothesized to be
      at lower risk of non-alcoholic fatty liver disease (NAFLD) because of higher
      insulin sensitivity. However, PWS patients have a peculiar body composition, i.e.
      higher fat mass and lower fat-free mass, which may confound such associations. We
      evaluated whether NAFLD is less frequent in PWS than in non-PWS women matched on
      percent body fat (PBF). METHODS: PBF was measured by dual-energy X-ray
      absorptiometry. Liver fat was assessed by ultrasonography. Insulin sensitivity
      and beta-cell function were evaluated by oral glucose tolerance testing.
      Coarsened exact matching (CEM) was used to match PWS and non-PWS women on PBF.
      General and generalized linear models taking CEM into account were used to
      perform comparisons between PWS and non-PWS women. RESULTS: 20 women with PWS
      were matched to 27 women without PWS on the basis of PBF (mean 53 vs. 54%, p =
      0.6). Insulin sensitivity and beta-cell function were similar in the two groups.
      However, the prevalence of NAFLD was 25% in PWS versus 59% in non-PWS women (p =
      0.04). CONCLUSION: NAFLD is less frequent in PWS than in non-PWS women but this
      finding is not associated with higher insulin sensitivity.

PMID- 24577230
TI  - Effect of N-acetylcysteine administration on the expression and activities of
      antioxidant enzymes and the malondialdehyde level in the blood of lead-exposed
      workers.
AB  - We investigated whether treatment with N-acetylcysteine (NAC) reduces oxidative
      stress intensity and restores the expression and activities of superoxide
      dismutase (Sod1, SOD), catalase (Cat, CAT) and glutathione peroxidase (Gpx1, GPx)
      in lead-exposed workers. The exposed population was divided randomly into two
      groups. Workers in the first group (reference group, n=49) were not administered
      any drugs, while workers in the second group (n=122) were treated with NAC at
      three doses for 12 weeks (200 mg, 400 mg, 800 mg/day). NAC administered orally to
      lead-exposed workers normalized antioxidant enzyme activities in blood cells.
      Oxidative stress intensity measured as malondialdehyde (MDA) levels in serum,
      leukocytes and erythrocytes significantly decreased after NAC administration. NAC
      may be an alternative therapy for chronic lead intoxication.

PMID- 24577229
TI  - Maternal exposure to titanium dioxide nanoparticles during pregnancy; impaired
      memory and decreased hippocampal cell proliferation in rat offspring.
AB  - Titanium dioxide nanoparticles (TiO2-NPs) are massively produced in the
      environment, and because of their wide usage, they are a potential risk of damage
      to human health. TiO2-NPs are often used as additives for paints, papers, and
      foods. The central nervous system (CNS), including hippocampal regions, is
      potentially susceptible targets for TiO2-NPs. This study aimed to determine the
      effects of exposure to TiO2-NPs during pregnancy on hippocampal cell
      proliferation and the learning and memory of offspring. Pregnant Wistar rats
      received intragastric TiO2-NPs (100 mg/kg body weight) daily from gestational day
      (GD) 2 to (GD) 21. Animals in the control group received the same volume of
      distilled water via gavage. After delivery, the one-day-old neonates were deeply
      anesthetized and weighed. They were then killed and the brains of each group were
      collected. Sections of the brains from the rat offspring were stained using Ki-67
      immunolabeling and the immunohistochemistry technique. Some of the male offspring
      (n=12 for each group) were weaned at postnatal day (PND21), and housed until
      adulthood (PND60). Then the learning and memory in animals of each group were
      evaluated using passive avoidance and Morris water maze tests. The immunolabeling
      of Ki-67 protein as a proliferating cell marker showed that TiO2-NPs
      significantly reduced cell proliferation in the hippocampus of the offspring
      (P<0.05). Moreover, both the Morris water maze test and the passive avoidance
      test showed that exposure to TiO2-NPs significantly impaired learning and memory
      in offspring (P<0.05). These results may provide basic experimental evidence for
      a better understanding of the neurotoxic effects of TiO2-NPs on neonatal and
      adult brains.

PMID- 24577231
TI  - Clinical features and treatment experience: a review of 292 Chinese cobra
      snakebites.
AB  - Although Chinese cobra snakebite is the most common type of snake venenation in
      China, it still lacks a comprehensive and systematic description. Hence, we aimed
      to study Chinese cobra bite cases with particular attention to demography,
      epidemiology and clinical profile. In this study, a total of 292 cases of Chinese
      cobra snakebite, presenting between January 1, 2008 and December 31, 2012, were
      retrospectively reviewed. To investigate the effect of treatment at different
      presentation times (time from snakebite to admission), the patients were divided
      into two groups: group A included 133 cases that presented <12 h after the bite;
      group B included 159 cases that presented >=12 h after the bite. To assess the
      correlation between application of a tourniquet and skin grafting, the cases were
      re-divided into two groups according to whether or not a tourniquet was used
      after the snakebite: tourniquet group (n=220) and non-tourniquet group (n=72).
      The results showed that Chinese cobra snakebites were most commonly seen during
      the summer, in the upper limbs, and in males, young adults, and snake-hunters.
      Group A experienced milder intoxication than group B (P<0.001). The rate of skin
      grafting was significantly higher in the tourniquet group (20.0%, compared with
      9.7% in the non-tourniquet group, P<0.05). The results of this study indicate
      that anti-cobra venom and swift admission (within 12 h of the snakebite) are
      recommended for Chinese cobra snakebite. Tourniquet use is not recommended.

PMID- 24577232
TI  - Effects of fullerene C60 nanoparticles on A549 cells.
AB  - Fullerene C60 nanoparticles (C60 NPs) have been widely applied in many fields due
      to their excellent physical and chemical properties. As production and
      applications of C60 NPs expand, public concern about the potential risk to human
      health has also risen. The toxicity of C60 NPs was evaluated by the CCK-8 assay
      using the cultured human epithelial cell line A549. Cellular uptake of the C60
      NPs was observed by TEM imaging. In our findings, C60 NPs could readily enter
      A549 cells and showed no significant toxicity. Exposure of cultured A549 cells to
      C60 NPs led to an increase of intracellular reactive oxygen species (ROS) while
      glutathione reductase activity was probably activated to generate more GSH to
      maintain a cellular oxidation-reduction equilibrium. The A549 cells responded to
      the ROS increases through the inauguration of autophagic responses, aimed at
      restoring cellular health and equilibrium. 

PMID- 24577233
TI  - MicroRNA-21 controls the development of osteoarthritis by targeting GDF-5 in
      chondrocytes.
AB  - Osteoarthritis is a common cause of functional deterioration in older adults and
      is an immense burden on the aging population. Altered chondrogenesis is the most
      important pathophysiological process involved in the development of
      osteoarthritis. However, the molecular mechanism underlying the regulation of
      chondrogenesis in patients with osteoarthritis requires further elucidation,
      particularly with respect to the role of microRNAs. MiR-21 expression in
      cartilage specimens was examined in 10 patients with knee osteoarthritis and 10
      traumatic amputees. The effect of miR-21 on chondrogenesis was also investigated
      in a chondrocyte cell line. The effect of miR-21 on the expression of growth
      differentiation factor 5 (GDF-5) was further assessed by luciferase reporter
      assay and western blot. We found that endogenous miR-21 is upregulated in
      osteoarthritis patients, and overexpression of miR-21 could attenuate the process
      of chondrogenesis. Furthermore, we identified GDF-5 as the direct target of miR
      21 during the regulation of chondrogenesis. Our data suggest that miR-21 has an
      important role in the pathogenesis of osteoarthritis and is a potential
      therapeutic target. 

PMID- 24577235
TI  - Impairments of interpersonal functioning: empathy and intimacy in borderline
      personality disorder.
AB  - Impairments of interpersonal functioning are central to borderline personality
      disorder (BPD). Patients with BPD suffer from severe psychosocial dysfunction in
      general and - among others - disturbed romantic relationships. Compounding the
      problem, the diagnosis of BPD interferes with therapeutic relationships and
      results in pejorative and discriminatory clinical practices. Previously,
      interpersonal dysfunction has been related to emotional dysregulation, behavioral
      dyscontrol, and impaired social cognition. However, these features may be
      intertwined yet separate. In this review, we will focus on disturbed empathy and
      intimacy as they are referred to as two discrete impairments of interpersonal
      functioning in the new DSM-5 Section III. The aim of this review is to contribute
      to a comprehensive, integral understanding of interpersonal dysfunction in BPD
      based on the behavioral and neurobiological studies available up to now. Despite
      some inconsistencies, behavioral studies in BPD patients indicate impaired
      cognitive and affective empathy particularly in complex and ecologically valid
      measurements. These findings are reflected even more consistently in functional
      magnet resonance imaging studies. Low quality of intimate relationships in BPD
      may at least partially result from lower mentalizing abilities and cognitive
      empathy, higher personal distress and affective empathy in the social context.
      Finally, the evaluation of the severity and quality of impairment of
      interpersonal functioning may enable clinicians and researchers to describe and
      to understand the mechanisms of interpersonal dysfunction better, and to improve
      the effectiveness of the treatment of patients with BPD.

PMID- 24577234
TI  - Heptachlor induced nigral dopaminergic neuronal loss and Parkinsonism-like
      movement deficits in mice.
AB  - Epidemiological studies have suggested an association between pesticide exposure
      and Parkinson's disease. In this study, we examined the neurotoxicity of an
      organochlorine pesticide, heptachlor, in vitro and in vivo. In cultured SH-SY5Y
      cells, heptachlor induced mitochondria-mediated apoptosis. When injected into
      mice intraperitoneally on a subchronic schedule, heptachlor induced selective
      loss of dopaminergic neurons in the substantia nigra pars compacta. In addition,
      the heptachlor injection induced gliosis of microglia and astrocytes selectively
      in the ventral midbrain area. When the general locomotor activities were
      monitored by open field test, the heptachlor injection did not induce any gross
      motor dysfunction. However, the compound induced Parkinsonism-like movement
      deficits when assessed by a gait and a pole test. These results suggest that
      heptachlor can induce Parkinson's disease-related neurotoxicities in vivo. 

PMID- 24577238
TI  - A recently evolved class of alternative 3'-terminal exons involved in cell cycle
      regulation by topoisomerase inhibitors.
AB  - Alternative 3'-terminal exons, which use intronic polyadenylation sites, are
      generally less conserved and expressed at lower levels than the last exon of
      genes. Here we discover a class of human genes, in which the last exon appeared
      recently during evolution, and the major gene product uses an alternative 3'
      terminal exon corresponding to the ancestral last exon of the gene. This novel
      class of alternative 3'-terminal exons are downregulated on a large scale by
      doxorubicin, a cytostatic drug targeting topoisomerase II, and play a role in
      cell cycle regulation, including centromere-kinetochore assembly. The RNA-binding
      protein HuR/ELAVL1 is a major regulator of this specific set of alternative 3'
      terminal exons. HuR binding to the alternative 3'-terminal exon in the pre
      messenger RNA promotes its splicing, and is reduced by topoisomerase inhibitors.
      These findings provide new insights into the evolution, function and molecular
      regulation of alternative 3'-terminal exons. 

PMID- 24577239
TI  - Elevated asymmetric dimethylarginine is associated with oxidant stress
      aggravation in patients with early stage autosomal dominant polycystic kidney
      disease.
AB  - BACKGROUND/AIMS: In experimental models of polycystic kidney disease impaired
      bioavailability of nitric oxide (NO) and elevated mRNA expression of oxidative
      stress markers at the kidney level was noted. However, clinical studies
      investigating the potential role of endothelial dysfunction and oxidative stress
      in the pathogenesis of autosomal dominant polycystic kidney disease (ADPKD) are
      limited. We evaluated asymmetric dimethylarginine (ADMA) as marker of NO synthase
      inhibitor as well as 15-F2t-Isoprostane and oxidized-low density lipoprotein
      (oxidized-LDL) as measures of oxidative stress in patients with early stages
      ADPKD. METHODS: We recruited 26 ADPKD patients (Group A) with modestly impaired
      renal function (eGFR 45-70 ml/min/1.73 m(2)), 26 age- and sex-matched ADPKD
      patients (Group B) with relatively preserved renal function (eGFR)>70 ml/min/1.73
      m(2)), and 26 age- and sex-matched controls (Group C). Determination of
      circulating levels of ADMA, 15-F2t-Isoprostane, oxidized-LDL and routine
      biochemistry was performed. RESULTS: Group A and B had significantly higher ADMA
      levels as compared to controls (1.68 +/- 0.7 vs 0.51 +/- 0.2 MUmol/l, P<0.001 and
      1.26 +/- 0.7 vs 0.51 +/- 0.2 MUmol/l, P<0.001, respectively). 15-F2t-IsoP and
      oxidized-LDL levels were also significantly higher in Group B relative to
      controls (788.8 +/- 185.0 vs 383.1 +/- 86.0 pgr/ml, P<0.001 and 11.4 +/- 6.6 vs
      6.4 +/- 2.6 EU/ml, P<0.05 respectively) and were further elevated in Group A. In
      correlation analysis, ADMA levels exhibited strong associations with levels of 15
      F2t-Isoprostane (r=0.811, P<0.001) and oxidized-LDL (r=0.788, P<0.001), whereas
      an inverse correlation was evident between ADMA and eGFR (r=-0.460, P<0.001).
      CONCLUSION: This study shows elevation in circulating levels of ADMA along with
      aggravation of oxidative stress from the early stages of ADPKD. (c) 2014 S.
      Karger AG, Basel.

PMID- 24577240
TI  - Processable 3-nm thick graphene platelets of high electrical conductivity and
      their epoxy composites.
AB  - Graphene platelets (GnPs) are a class of novel 2D nanomaterials owing to their
      very small thickness (~3 nm), high mechanical strength and electric conductivity
      (1460 S cm(-1)), and good compatibility with most polymers as well as cost
      effectiveness. In this paper we present a low-cost processing technique for
      producing modified GnPs and an investigation of the electrical and mechanical
      properties of the resulting composites. After dispersing GnPs in solvent N-methyl
      2-pyrrolidone, a long-chain surfactant (Jeffamine D 2000, denoted J2000) was
      added to covalently modify GnPs, yielding J2000-GnPs. By adjusting the ratio of
      GnPs to the solvent, the modified GnPs show different average thickness and thus
      electrical conductivity ranging from 694 to 1200 S cm(-1). To promote the
      exfoliation and dispersion of J2000-GnPs in a polymeric matrix, they were
      dispersed in the solvent again and further modified using diglycidyl ether of
      bisphenol A (DGEBA) producing m-GnPs, which were then compounded with an epoxy
      resin for the development of epoxy/m-GnP composites. A percolation threshold of
      electrical volume resistivity for the resulting composites was observed at 0.31
      vol%. It was found that epoxy/m-GnP composites demonstrated far better mechanical
      properties than those of unmodified GnPs of the same volume fraction. For
      example, m-GnPs at 0.25 vol% increased the fracture energy release rate G1c from
      0.204 +/- 0.03 to 1.422 +/- 0.24 kJ m(-2), while the same fraction of unmodified
      GnPs increased G1c to 1.01 +/- 0.24 kJ m(-2). The interface modification also
      enhanced the glass transition temperature of neat epoxy from 58.9 to 73.8 
      degrees C.

PMID- 24577241
TI  - Acute panretinal structural and functional abnormalities after intravitreous
      ocriplasmin injection.
AB  - IMPORTANCE Ocriplasmin cleaves fibronectin and laminin, components of the
      vitreous gel, and is used as a pharmacologic treatment for vitreomacular
      traction. Laminin is also found throughout multiple retinal layers. Ocriplasmin
      injection may lead to acute panretinal dysfunction in some eyes, but the
      mechanism of this toxic reaction has not been described. OBSERVATIONS We
      evaluated a 63-year-old woman demonstrating acute panretinal dysfunction after
      intravitreous ocriplasmin injection for a small macular hole with vitreomacular
      adhesion. Findings included visual acuity loss, visual field constriction,
      pupillary abnormalities, attenuated retinal arteries, loss of outer retinal
      signals on spectral-domain optical coherence tomography, and severely reduced
      electroretinography responses. B-waves were reduced more than A-waves were,
      suggesting postreceptoral dysfunction and decreased photoreceptor activity.
      CONCLUSIONS AND RELEVANCE Retinal dysfunction associated with intravitreous
      ocriplasmin injection is not limited to the macular region and seems to involve
      the entire retina. Enzymatic cleavage of intraretinal laminin is a biologically
      plausible mechanism for acute ocriplasmin retinal toxic effects. 

PMID- 24577243
TI  - Assessment of hypoxia in the stroma of patient-derived pancreatic tumor
      xenografts.
AB  - The unusually dense stroma of pancreatic cancers is thought to play an important
      role in their biological aggression. The presence of hypoxia is also considered
      an adverse prognostic factor. Although it is usually assumed that this is the
      result of effects of hypoxia on the epithelial component, it is possible that
      hypoxia exerts indirect effects via the tumor stroma. We therefore measured
      hypoxia in the stroma of a series of primary pancreatic cancer xenografts. Nine
      patient-derived pancreatic xenografts representing a range of oxygenation levels
      were labeled by immunohistochemistry for EF5 and analyzed using semi-automated
      pattern recognition software. Hypoxia in the tumor and stroma was correlated with
      tumor growth and metastatic potential. The extent of hypoxia varied from 1%-39%
      between the different models. EF5 labeling in the stroma ranged from 0-20%
      between models, and was correlated with the level of hypoxia in the tumor cell
      area, but not microvessel density. Tumor hypoxia correlated with spontaneous
      metastasis formation with the exception of one hypoxic model that showed
      disproportionately low levels of hypoxia in the stroma and was non-metastatic.
      Our results demonstrate that hypoxia exists in the stroma of primary pancreatic
      cancer xenografts and suggest that stromal hypoxia impacts the metastatic
      potential. 

PMID- 24577244
TI  - A supramolecular hydrogel as a carrier to deliver microRNA into the encapsulated
      cells.
AB  - A supramolecular hydrogel formed by dipeptide Gly-Ala linked with biphenyl
      substituted tetrazole serves not only as a 3D matrix for live cells, but also as
      a carrier to deliver microRNA into the encapsulated cells. 

PMID- 24577242
TI  - The role of cyclic nucleotide signaling pathways in cancer: targets for
      prevention and treatment.
AB  - For more than four decades, the cyclic nucleotides cyclic AMP (cAMP) and cyclic
      GMP (cGMP) have been recognized as important signaling molecules within cells.
      Under normal physiological conditions, cyclic nucleotides regulate a myriad of
      biological processes such as cell growth and adhesion, energy homeostasis,
      neuronal signaling, and muscle relaxation. In addition, altered cyclic nucleotide
      signaling has been observed in a number of pathophysiological conditions,
      including cancer. While the distinct molecular alterations responsible for these
      effects vary depending on the specific cancer type, several studies have
      demonstrated that activation of cyclic nucleotide signaling through one of three
      mechanisms-induction of cyclic nucleotide synthesis, inhibition of cyclic
      nucleotide degradation, or activation of cyclic nucleotide receptors-is
      sufficient to inhibit proliferation and activate apoptosis in many types of
      cancer cells. These findings suggest that targeting cyclic nucleotide signaling
      can provide a strategy for the discovery of novel agents for the prevention
      and/or treatment of selected cancers. 

PMID- 24577247
TI  - Patents running out: time to take stock of robotic surgery.

PMID- 24577248
TI  - Anion exchange in [Ni(eta(5)-C(5)H(4)R)(Cl)(NHC)]. Counterion effect on the
      structure and catalytic activity.
AB  - A series of novel complexes [Ni(eta(5)-C5H4R)(L)(NHC)](+)A(-)2a-2j and [Ni(eta(5)
      C5H5)(A)(NHC)] 3a-3c has been obtained by anion metathesis from the corresponding
      chlorides 1a-1d, depending on the anion binding properties and reaction
      conditions. Solid-state structures of two cationic complexes (2c, 2j) and two
      complexes with a coordinated anion (3a, 3c) have been determined by X-ray
      diffraction revealing a trigonal planar geometry in all cases. Unexpectedly, 3c
      displayed unprecedented for this type of compounds temperature-dependent NMR
      spectra that were interpreted in terms of spin equilibrium. The cationic
      complexes 2 were less efficient in styrene polymerization than the parent
      chlorides 1. However, the activity of 2 and 3 in Suzuki cross-coupling did not
      depend considerably on the counterion. 

PMID- 24577249
TI  - Polymorphisms of the endothelial nitric oxide synthase gene in preeclampsia in a
      Han Chinese population.
AB  - BACKGROUND/AIMS: The endothelial nitric oxide synthase (eNOS) gene has been
      enlisted by previous research as a candidate gene of preeclampsia predisposition.
      This study investigates the specific roles of 3 polymorphisms of the eNOS gene in
      a population of Chinese origin from mainland China. METHODS: We studied the
      association of 3 commonly studied polymorphisms of the eNOS gene, namely 4b/a, T
      786C and Glu298Asp, in a case-controlled sample of 220 patients diagnosed with
      preeclampsia and 200 healthy controls. The association between eNOS polymorphisms
      and preeclampsia was evaluated by performing genotyping for the eNOS variants and
      calculating odds ratios (OR) and 95% confidence intervals. The plasma nitrite
      concentration in participants was determined to examine how 3 eNOS polymorphisms
      affect plasma nitric oxide (NO) concentrations in pregnant women. RESULTS: The
      frequencies of both the variant 298Asp allele and eNOS 4a allele were
      significantly lower in preeclamptic women than in the control group and had a
      significantly lower OR. The variant 298Asp allele and eNOS 4a are strongly
      associated with higher plasma NO concentrations in pregnant women. CONCLUSIONS:
      Polymorphisms in the eNOS gene may be protective against preeclampsia in a
      Chinese population, and this protective effect may be associated with NO
      formation in plasma in pregnant women.

PMID- 24577250
TI  - Changes in cytokines in tears after endoscopic endonasal dacryocystorhinostomy
      for primary acquired nasolacrimal duct obstruction.
AB  - PURPOSE: We attempted to compare the cytokine composition of tears between
      primary acquired nasolacrimal duct (NLD) obstruction and normal controls. We
      investigated the changes in cytokines in tears after endoscopic endonasal
      dacryocystorhinostomy (DCR). PATIENTS AND METHODS: Eighteen patients underwent
      endonasal DCR, with seven patients undergoing bilateral DCR, resulting in twenty
      five DCRs in total. Eleven contralateral un-operated eyes were used as normal
      controls. Silicone stents were removed 3 months after surgery. Tear samples were
      collected from all eyes before surgery, and at 1 month, 2 months, 3 months, and 4
      months after surgery. The level of interleukin (IL)-1beta, IL-2, IL-6, IL-10,
      transforming growth factor (TGF)-beta2, fibroblast growth factor (FGF)-2, and
      vascular endothelial growth factor (VEGF) in the tears was measured. RESULTS: The
      concentrations of IL-2, IL-6, IL-10, VEGF, and FGF-2 were significantly higher in
      eyes with NLD obstruction than controls before surgery (P=0.006, 0.018, 0.002,
      0.048, and 0.039, respectively). Most inflammatory cytokines (IL-1beta, IL-2, IL
      6, VEGF, and FGF-2) were higher in the tears of the DCR group compared with the
      controls during the postoperative follow-up, but then rapidly decreased to the
      level of the controls after removal of the silicone stent. The recurred eyes
      showed a higher level of TGF-beta2 and FGF-2 in tears compared with the eyes that
      showed good surgical results (P<0.005 and <0.005, respectively). CONCLUSION: The
      tear levels of inflammatory cytokines were higher in eyes with NLD obstruction
      than controls. The changes in cytokine level during the postoperative period
      showed the importance of cytokine analysis in understanding wound healing after
      DCR.

PMID- 24577252
TI  - Infraorbital nerve enlargement due to IgG4-related disease.

PMID- 24577245
TI  - Psychiatric disorders from childhood to adulthood in 22q11.2 deletion syndrome:
      results from the International Consortium on Brain and Behavior in 22q11.2
      Deletion Syndrome.
AB  - OBJECTIVE: Chromosome 22q11.2 deletion syndrome is a neurogenetic disorder
      associated with high rates of schizophrenia and other psychiatric conditions. The
      authors report what is to their knowledge the first large-scale collaborative
      study of rates and sex distributions of psychiatric disorders from childhood to
      adulthood in 22q11.2 deletion syndrome. The associations among psychopathology,
      intellect, and functioning were examined in a subgroup of participants. METHOD:
      The 1,402 participants with 22q11.2 deletion syndrome, ages 6-68 years, were
      assessed for psychiatric disorders with validated diagnostic instruments. Data on
      intelligence and adaptive functioning were available for 183 participants ages 6
      to 24 years. RESULTS: Attention deficit hyperactivity disorder (ADHD) was the
      most frequent disorder in children (37.10%) and was overrepresented in males.
      Anxiety disorders were more prevalent than mood disorders at all ages, but
      especially in children and adolescents. Anxiety and unipolar mood disorders were
      overrepresented in females. Psychotic disorders were present in 41% of adults
      over age 25. Males did not predominate in psychotic or autism spectrum disorders.
      Hierarchical regressions in the subgroup revealed that daily living skills were
      predicted by the presence of anxiety disorders. Psychopathology was not
      associated with communication or socialization skills. CONCLUSIONS: To the
      authors' knowledge, this is the largest study of psychiatric morbidity in 22q11.2
      deletion syndrome. It validates previous findings that this condition is one of
      the strongest risk factors for psychosis. Anxiety and developmental disorders
      were also prevalent. These results highlight the need to monitor and reduce the
      long-term burden of psychopathology in 22q11.2 deletion syndrome.

PMID- 24577251
TI  - Intermittent exotropia: relation between age and surgical outcome: a change-point
      analysis.
AB  - PURPOSE: To study the relationship between age and response to surgery in
      patients with intermittent exotropia and to identify change points in response to
      surgery. METHODS: A retrospective analysis was conducted on 311 patients with
      intermittent exotropia who had bilateral lateral rectus recession using standard
      tables with minimum follow-up of 6 months. Data were analyzed using the change
      point analysis software to identify cutoff points. A prospective pilot study was
      then performed on 171 consecutive patients with intermittent exotropia with the
      same clinical characteristics, in whom amount of recession was modified according
      to the identified cutoff points. In angles with two change points, 1-mm recession
      was reduced from patients younger than the lower change point and 1.5-mm
      recession was added to those older than the upper change point. In angles with
      one change point, 1.5-mm recession was added to those older than the change
      point. Satisfactory alignment was defined as esophoria/tropia <= 5Delta to
      exophoria/tropia <= 8Delta. RESULTS: There was a negative correlation (P<0.01)
      between response to surgery and age at surgery for all angles. In younger
      patients (<7 years) in whom surgical dose was reduced, there was no significant
      change in success rate (77%), compared with those who had surgery using standard
      tables (75%). In older patients (>12 years) in whom surgical dose was increased,
      there was a statistically significant increase in success rate (80% vs 41%).
      CONCLUSIONS: Modifying the surgical dose according to age can improve the success
      in patients with intermittent exotropia.

PMID- 24577254
TI  - Spectral domain optical coherence tomography features in niacin maculopathy.

PMID- 24577253
TI  - Influence of cycloplegia with topical cyclopentolate on higher-order aberrations
      in myopic children.
AB  - PURPOSE: To investigate the influence of cycloplegia with topical cyclopentolate
      on wavefront aberrations in myopic children. DESIGN: This is a prospective,
      comparative study. METHODS: Twenty-eight myopic children with a mean age of 7.25
      +/- 2.55 were enrolled in this study. We evaluated refraction and wavefront
      aberrations before and after cycloplegia with 1% cyclopentolate hydrochloride.
      Ocular and corneal aberrations were simultaneously measured and compared with
      each other. Individual Zernike components were also analyzed up to the sixth
      order. All these parameters were compared before and after cycloplegia. RESULTS:
      Ocular higher-order aberrations (HOAs) significantly increased after cycloplegia
      (P=0.012 for spherical-like and P=0.015 for total HOAs). Corneal HOAs did not
      change after cycloplegia. When corneal and ocular HOAs were compared, the ocular
      HOAs were significantly smaller than the corneal HOAs in spherical-like
      aberrations (P<0.001) and total HOAs (P=0.006). As for individual Zernike
      components, ocular aberration generally showed smaller or equivalent values in
      comparison with corneal aberration. In addition, each Zernike component showed a
      large standard deviation. CONCLUSIONS: Internal optics compensates for corneal
      HOAs in myopic children, and paralysis of tonic accommodation with cyclopentolate
      considerably affects ocular HOAs. However, inter-individual variation in each
      Zernike component is quite large in myopic children.

PMID- 24577255
TI  - New 1,2,4-triazole-based azo-azomethine dye. Part III: Synthesis,
      characterization, thermal property, spectrophotometric and computational studies.
AB  - A new 1,2,4-triazole-based azo-azomethine compound, H2L, has been prepared by
      condensation reaction of 1-(3-formyl-4-hydroxyphenylazo)-4-ethylbenzene with
      prepared triazole-based diamine. The structure of H2L was characterized by using
      FT-IR, UV-Vis and (1)H NMR spectroscopic methods as well as elemental analysis.
      Hard model chemometrics method has been used to determine the formation constants
      of zinc(II), copper(II), nickel(II) and cobalt(II) complexes of H2L in DMSO by UV
      Vis spectrophotometric method. Solvatochromic behavior of the dye has been also
      investigated in some organic solvents with different polarities. Thermal
      properties of the prepared dye was examined by thermogravimetric analysis.
      Results indicated that the framework of the dye was stable up to 245  degrees C.
      Furthermore,(1)H chemical shifts and UV-Vis of H2L were studied by the gauge
      independent atomic orbital (GIAO), continuous set of gauge transformations (CSGT)
      and time-dependent density functional theory (TD-DFT) methods respectively at the
      level of density functional theory using B3LYP/6-311+G(d) basis sets in DMSO. The
      computational data are in reasonably good agreement with the experimental data.

PMID- 24577256
TI  - Severity but not comorbidities predicts response to methylphenidate in adults
      with attention-deficit/hyperactivity disorder: results from a naturalistic study.
AB  - Although the identification of reliable predictors of methylphenidate response in
      adults with attention-deficit/hyperactivity disorder (ADHD) is necessary to guide
      treatment decisions, very few data exist on this issue. Here, we assessed the
      predictors of clinical response to immediate-release methylphenidate
      hydrochloride (IR-MPH) in a naturalistic setting by analyzing the influence of
      demographic factors, severity, and a wide range of comorbid psychiatric
      disorders. Two hundred fifty adult patients with ADHD were evaluated and
      completed a short-term treatment with IR-MPH. Mental health diagnoses were based
      on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition,
      criteria through the use of standard structured interviews. The Swanson, Nolan,
      and Pelham Rating Scale, version 4, adapted to adults was used to assess the
      severity of ADHD. In the linear regression model, only higher severity of ADHD
      was associated to a better IR-MPH response (b = 0.770; P < 0.001). Treatment of
      comorbidities in a subsample (n = 62) did not modify this pattern. Our findings
      suggest that in clinical settings, patients with more severe ADHD symptoms have a
      good response to treatment independently from the presence of mild or stabilized
      comorbidities and their treatments. For adults with ADHD, differently from other
      common psychiatric disorders such as depression and anxiety, higher severity is
      associated with better treatment response. 

PMID- 24577257
TI  - Prolonged penile erections associated with the use of atomoxetine and
      aripiprazole in an 11-year-old boy.

PMID- 24577258
TI  - Cutaneous actinomycosis associated with anti-TNF-alpha therapy: report of two
      cases.
AB  - Increased susceptibility to infections is among the main safety concerns raised
      by anti-TNF-alpha agents. We describe two cases of cutaneous actinomycosis in
      patients undergoing anti-TNF-alpha therapy: a 49-year-old female treated with
      etanercept for rheumatoid arthritis and a 57-year-old female treated with
      infliximab for psoriasis. Both patients had discharge with the intermittent
      presence of sulfur granules occurring at the site of previous surgical wounds.
      Bacteriological culture demonstrated Actinomyces. Since in both cases laboratory
      findings and medical imaging ruled out visceral actinomycosis, oral antibiotics
      were introduced without discontinuing anti-TNF-alpha. The first patient did not
      relapse after 2 years. The second one did and received a second course of
      antibiotics combined with transient interruption of the anti-TNF-alpha therapy.
      The risk of developing actinomycosis is reported to be similar in immunocompetent
      and immunocompromised patients, however cases of cutaneous actinomycosis
      occurring during anti-TNF-alpha therapy need to be recognized and may be under
      reported.

PMID- 24577259
TI  - Competition-driven speciation in cichlid fish.
AB  - Theoretically, competition can initiate divergence in habitat use between
      individuals of a species, leading to restricted gene flow and eventual
      speciation. Evidence that sister species differ in habitat use is commonplace and
      consistent with this mechanism, but empirical experimental support is
      surprisingly scarce. Here we provide evidence that competition has taken a key
      role in the evolution of genetically distinct ecomorphs of the Lake Tanganyika
      cichlid fish Telmatochromis temporalis. Experiments show that differences in
      substrate use between a large-bodied rock-living ecomorph and a neighbouring
      small-bodied shell-living ecomorph are mediated by size-dependent competition
      that drives assortative mate-pair formation. Specifically, adults of the larger
      ecomorph outcompete adults of the smaller ecomorph on favoured rock substrate,
      compelling the smaller adults to use shell habitat. These results support a role
      for competition in maintaining reproductive isolation, and highlight the need to
      identify ecological processes that impose selection to improve our understanding
      of speciation and adaptive radiation. 

PMID- 24577260
TI  - Analysis of relative expression level of VEGF ( vascular endothelial growth
      factor ), HIF-1alpha ( hypoxia inducible factor 1alpha ) and CTGF ( connective
      tissue growth factor ) genes in chronic glomerulonephritis (CGN) patients.
AB  - BACKGROUND/AIMS: Analysis of gene expression in renal tissue is considered to be
      a diagnostic tool predicting the clinical course of glomerulonephritis. The
      present study quantified the relative transcript levels of VEGF, CTGF and HIF
      1alpha in renal tissue to establish their relationship with some clinical
      variables in patients suffering from chronic glomerulonephritis (CGN). METHODS:
      28 patients (6F and 22M, mean age 51.2+/-15.0) with CGN were enrolled. Type of
      CNG recognized by kidney biopsy (histopatological evaluation) was as follows:
      minimal change disease (MCD)-3pts, IgA nephropathy-5pts, FSGS-3pts, membranous
      nephropathy-4pts, mesangio-proliferative glomerulonephritis-3pts; MPGN-1pts,
      lupus nephritis-6pts, granulomatosis with polyangitis-2 pts; hypertensive
      nephropathy- 3pts. Renal tissue from 3 individuals with normal eGFR and histology
      was taken as control. Mean clinical follow-up of patients was 12 months after
      biopsy eGFR and daily urinary protein excretion (DPE) was assessed at the time of
      biopsy and then in 6 months intervals. Real-time PCR was used to determine
      relative gene expression. The housekeeping gene GAPDH was used as normalization
      control. RESULTS: At the time of the biopsy relative expression of 3 analyzed
      genes was diminished in comparison to control. There were statistically
      significant differences in VEGF gene relative expression level in patients which
      varied according to eGFR and tendency in patients which varied according to DPE.
      HIF-alfa and CTGF gene showed only a tendency. CONCLUSIONS: Overexpression of the
      VEGF gene in subjects with DPE>3,5 g may point to insufficient oxygen supply in
      renal tissue which may result in tubulointerstitial fibrosis with further
      functional renal impairment and decline of eGFR.

PMID- 24577261
TI  - Acoustic impedance rhinometry (AIR): a technique for monitoring dynamic changes
      in nasal congestion.
AB  - We describe a simple and inexpensive method for monitoring nasal air flow
      resistance using measurement of the small-signal acoustic input impedance of the
      nasal passage, similar to the audiological measurement of ear drum compliance
      with acoustic tympanometry. The method requires generation of a fixed sinusoidal
      volume-velocity stimulus using ear-bud speakers, and an electret microphone to
      monitor the resultant pressure fluctuation in the nasal passage. Both are coupled
      to the nose via high impedance silastic tubing and a small plastic nose insert.
      The acoustic impedance is monitored in real-time using a laptop soundcard and
      custom-written software developed in LabView 7.0 (National Instruments). The
      compact, lightweight equipment and fast time resolution lends the technique to
      research into the small and rapid reflexive changes in nasal resistance caused by
      environmental and local neurological influences. The acoustic impedance
      rhinometry technique has the potential to be developed for use in a clinical
      setting, where the need exists for a simple and inexpensive objective nasal
      resistance measurement technique. 

PMID- 24577262
TI  - [Delayed wound healing during therapy of cutaneous graft-versus-host disease with
      everolimus].
AB  - Graft-versus-host-disease (GvHD) is despite improvement in transplantation
      medicine the major cause for morbidity and mortality after allogeneic stem cell
      transplantation. We describe a patient with chronic cutaneous GvHD who developed
      massive skin ulcerations after changing the immunosuppressive therapy to a
      mammalian target of rapamycin (mTOR)-inhibitor.

PMID- 24577264
TI  - Organometal halide perovskites as useful materials in sensitized solar cells.
AB  - Organometal halide perovskites offer dual potential properties as a light
      harvester and at the same time as a hole conductor in inorganic-organic hybrid
      heterojunction solar cells. The sequential deposition route provides a power
      conversion efficiency of 15% under standard AM1.5G test conditions. In this
      perspective, we will briefly summarize the development of perovskite-sensitized
      solar cells from their first report up to the present. 

PMID- 24577263
TI  - Large cities are less green.
AB  - We study how urban quality evolves as a result of carbon dioxide emissions as
      urban agglomerations grow. We employ a bottom-up approach combining two
      unprecedented microscopic data on population and carbon dioxide emissions in the
      continental US. We first aggregate settlements that are close to each other into
      cities using the City Clustering Algorithm (CCA) defining cities beyond the
      administrative boundaries. Then, we use data on CO2 emissions at a fine
      geographic scale to determine the total emissions of each city. We find a
      superlinear scaling behavior, expressed by a power-law, between CO2 emissions and
      city population with average allometric exponent beta = 1.46 across all cities in
      the US. This result suggests that the high productivity of large cities is done
      at the expense of a proportionally larger amount of emissions compared to small
      cities. Furthermore, our results are substantially different from those obtained
      by the standard administrative definition of cities, i.e. Metropolitan
      Statistical Area (MSA). Specifically, MSAs display isometric scaling emissions
      and we argue that this discrepancy is due to the overestimation of MSA areas. The
      results suggest that allometric studies based on administrative boundaries to
      define cities may suffer from endogeneity bias. 

PMID- 24577265
TI  - Involvement of DNMT3B in the pathogenesis of Hirschsprung disease and its
      possible role as a regulator of neurogenesis in the human enteric nervous system.
AB  - PURPOSE: Hirschsprung disease (OMIM 142623) is a neurocristopathy attributed to a
      failure of cell proliferation or migration and/or failure of the enteric
      precursors along the gut to differentiate during embryonic development. Although
      some genes involved in this pathology are well characterized, many aspects remain
      poorly understood. In this study, we aimed to identify novel genes implicated in
      the pathogenesis of Hirschsprung disease. METHODS: We compared the expression
      patterns of genes involved in human stem cell pluripotency between enteric
      precursors from controls and Hirschsprung disease patients. We further evaluated
      the role of DNMT3B in the context of Hirschsprung disease by inmunocytochemistry,
      global DNA methylation assays, and mutational screening. RESULTS: Seven
      differentially expressed genes were identified. We focused on DNMT3B, which
      encodes a DNA methyltransferase that performs de novo DNA methylation during
      embryonic development. DNMT3B mutational analysis in our Hirschsprung disease
      series revealed the presence of potentially pathogenic mutations (p.Gly25Arg,
      p.Arg190Cys, and p.Gly198Trp). CONCLUSION: DNMT3B may be regulating enteric
      nervous system development through DNA methylation in the neural crest cells,
      suggesting that aberrant methylation patterns could have a relevant role in
      Hirschsprung disease. Moreover, the synergistic effect of mutations in both
      DNMT3B and other Hirschsprung disease-related genes may be contributing to a more
      severe phenotype in our Hirschsprung disease patients.

PMID- 24577267
TI  - Results of the College of American Pathology/American College of Medical Genetics
      and Genomics external proficiency testing from 2006 to 2013 for three conditions
      prevalent in the Ashkenazi Jewish population.
AB  - PURPOSE: The purpose of this study was to determine analytic performance of
      laboratories offering molecular testing for conditions such as Tay-Sachs disease,
      Canavan disease, and familial dysautonomia, which are prevalent in the Ashkenazi
      Jewish population. METHODS: The College of American Pathologists and the American
      College of Medical Genetics and Genomics cosponsor molecular proficiency testing
      for these disorders. Responses from 2006 to 2013 were analyzed for accuracy
      (genotyping and interpretations). RESULTS: Between 11 and 36 laboratories
      participated in each Tay-Sachs disease distribution. Samples tested per month
      were constant (2,900) from 2006 to 2011 but recently increased. Participants
      reporting <10 samples tested per month had longer turnaround times (42 vs. 7%,
      longer than 14 days; P = 0.03). Analytic sensitivity and specificity for US
      participants were 97.2% (95% confidence interval: 94.7-98.7%) and 99.8% (95%
      confidence interval: 99.1-99.9%), respectively. Of 11 genotyping errors, 2 were
      due to sample mix-up. Analytic interpretations were correct in 99.3% of
      challenges (956/963; 95% confidence interval: 98.5-99.7%). Better performance was
      found for Canavan disease and familial dysautonomia. International laboratories
      performed equally well. CONCLUSION: These results demonstrated high analytic
      sensitivity and specificity along with excellent analytic interpretation
      performance, confirming the genetics community impression that laboratories
      provide accurate test results in both diagnostic and screening settings.
      Proficiency testing can identify potential laboratory issues and helps document
      overall laboratory performance.

PMID- 24577266
TI  - Loeys-Dietz syndrome: a primer for diagnosis and management.
AB  - Loeys-Dietz syndrome is a connective tissue disorder predisposing individuals to
      aortic and arterial aneurysms. Presenting with a wide spectrum of multisystem
      involvement, medical management for some individuals is complex. This review of
      literature and expert opinion aims to provide medical guidelines for care of
      individuals with Loeys-Dietz syndrome.

PMID- 24577268
TI  - Acquisition frame rate affects microtubule plus-end tracking analysis.

PMID- 24577269
TI  - Reply to "Acquisition frame rate affects microtubule plus-end tracking analysis".

PMID- 24577270
TI  - Protein digestion priority is independent of protein abundances.

PMID- 24577271
TI  - A Drosophila RNAi collection is subject to dominant phenotypic effects.

PMID- 24577272
TI  - Art and artifacts in single-molecule localization microscopy: beyond attractive
      images.

PMID- 24577273
TI  - PCR: paths to sensitivity.

PMID- 24577274
TI  - A particle tracking meet.

PMID- 24577275
TI  - Genome editing 101: let's go digital.

PMID- 24577278
TI  - 3-(7-Dimethylamino)coumarin N-phenylsemicarbazones in solution and polymer
      matrices: Tuning their fluorescence via para-phenyl substitution.
AB  - The photo-physical properties of five new para-phenyl substituted derivatives of
      3-(7-dimethylamino)coumarin N-phenylsemicarbazone with various electron
      withdrawing substituents R (RF, Br, CF3, CN or NO2) in the para-position on the
      phenyl ring were investigated in solvents and in polymer matrices. Tuning their
      fluorescent properties via para-substitution is discussed in terms of Twisted
      Intra-molecular Charge-Transfer (TICT) state formation, specific solute-solvent
      interactions (hydrogen bonding), fluorescent H-aggregates formation, and the
      solvent polarity and polymer matrix effects. 

PMID- 24577279
TI  - Placental pathology in early-onset and late-onset fetal growth restriction.
AB  - Several histopathological features are found more frequently in placentas from
      pregnancies complicated by fetal growth restriction (FGR), including villous
      infarction, maternal vascular changes and villous morphological alterations,
      although around one quarter of placentas associated with FGR lack any
      morphological abnormality on routine examination. Since similar changes may also
      affect clinically uncomplicated pregnancies, the positive predictive value of
      such findings for pathological FGR in an unselected case remains low. However,
      the pattern of placental pathologies varies with clinical subgroup. The
      combination of placental bed and parenchymal lesions in FGR with abnormal uterine
      artery Doppler velocimetry is essentially identical to preterm pre-eclampsia
      (PET), and there is an association between FGR with abnormal umbilical artery
      Doppler findings and lesions of fetal stem arteries and terminal villous
      hypovascularity. Conversely, placentas from pregnancies complicated by PET or FGR
      presenting at or near term have a significantly lower frequency of histological
      abnormalities compared to early-onset disease and absence of a distinctive
      biochemical profile. The histological placental findings in FGR are therefore
      varied, from morphologically unremarkable through to severe uteroplacental
      vasculopathy, with no single pathological feature associated with high
      sensitivity or specificity. Severe early-onset FGR, overlapping with severe early
      onset PET, is mainly associated with features of impaired maternal uteroplacental
      perfusion secondary to defective extravillous trophoblast invasion, and its
      consequences. Late-onset FGR probably represents a more heterogeneous group with
      less characteristic histological changes. Future research using histopathological
      assessment of aggregated data from multiple studies into larger datasets with
      centralised pathology review will allow delineation of distinctive
      clinicopathological associations and further understanding of pathophysiology.

PMID- 24577277
TI  - Fluorophore localization algorithms for super-resolution microscopy.
AB  - Super-resolution localization microscopy methods provide powerful new
      capabilities for probing biology at the nanometer scale via fluorescence. These
      methods rely on two key innovations: switchable fluorophores (which blink on and
      off and can be sequentially imaged) and powerful localization algorithms (which
      estimate the positions of the fluorophores in the images). These techniques have
      spurred a flurry of innovation in algorithm development over the last several
      years. In this Review, we survey the fundamental issues for single-fluorophore
      fitting routines, localization algorithms based on principles other than fitting,
      three-dimensional imaging, dipole imaging and techniques for estimating
      fluorophore positions from images of multiple activated fluorophores. We offer
      practical advice for users and adopters of algorithms, and we identify areas for
      further development. 

PMID- 24577276
TI  - Precisely and accurately localizing single emitters in fluorescence microscopy.
AB  - Methods based on single-molecule localization and photophysics have brought
      nanoscale imaging with visible light into reach. This has enabled single-particle
      tracking applications for studying the dynamics of molecules and nanoparticles
      and contributed to the recent revolution in super-resolution localization
      microscopy techniques. Crucial to the optimization of such methods are the
      precision and accuracy with which single fluorophores and nanoparticles can be
      localized. We present a lucid synthesis of the developments on this localization
      precision and accuracy and their practical implications in order to guide the
      increasing number of researchers using single-particle tracking and super
      resolution localization microscopy. 

PMID- 24577280
TI  - Systematic review focusing on the excretion and protection roles of sweat in the
      skin.
AB  - The skin excretes substances primarily through sweat glands. Several conditions
      have been demonstrated to be associated with diminished sweating. However, few
      studies have concentrated on the metabolism and excretion of sweat. This review
      focuses on the relationship between temperature and the thermoregulatory efficacy
      of sweat, and then discusses the excretion of sweat, which includes the
      metabolism of water, minerals, proteins, vitamins as well as toxic substances.
      The potential role of sweat secretion in hormone homeostasis and the effects on
      the defense system of the skin are also clarified.

PMID- 24577281
TI  - Changes of heavy metals in Pollutant Release and Transfer Registers (PRTRs) in
      Korea.
AB  - Industrial effluent containing heavy metals discharged into streams may pose high
      toxicity risks to aquatic organisms and to human health. Therefore, it is
      important to understand how to change the amount of effluent with heavy metals
      discharged from industries into open aquatic ecosystems both for effective
      management of heavy metals and to foster sustainable ecosystems. This study was
      conducted to characterize the release of heavy metals from industries based on
      the Pollutant Release and Transfer Registers database in Korea from 1999 to 2010.
      From the database, we selected nine heavy metals (Pb, Cd, Mn, Sb, Cu, Zn, Cr, Sn,
      and Ni) and compared the differences in their effluent for different types of
      industries. The heavy metal effluents released into freshwater ecosystems were
      classified into four clusters through the learning process of the self-organizing
      map. Cluster 1 was characterized by the relatively higher effluent volumes of
      heavy metals, whereas cluster 4 had lower effluent volumes. The different
      patterns of the effluent volumes in heavy metals were closely associated with the
      differences of industrial types, and the changes of effluents of heavy metals
      reflected the changes in regulations and laws for aquatic ecosystem management. 

PMID- 24577282
TI  - Life gain in Italian smokers who quit.
AB  - This study aims to estimate the number of life years gained with quitting smoking
      in Italian smokers of both sexes, by number of cigarettes smoked per day
      (cig/day) and age at cessation. All-cause mortality tables by age, sex and
      smoking status were computed, based on Italian smoking data, and the survival
      curves of former and current smokers were compared. The more cig/day a man/woman
      smokes, and the younger his/her age of quitting smoking, the more years of life
      he/she gains with cessation. In fact, cessation at age 30, 40, 50, or 60 years
      gained, respectively, about 7, 7, 6, or 5, and 5, 5, 4, or 3 years of life,
      respectively, for men and women that smoked 10-19 cig/day. The gain in life years
      was higher for heavy smokers (9 years for >20 cig/day) and lower for light
      smokers (4 years for 1-9 cig/day). Consistently with prospective studies
      conducted worldwide, quitting smoking increases life expectancy regardless of
      age, gender and number of cig/day. The estimates of the number of years of life
      that could be gained by quitting smoking, when computed specifically for a single
      smoker, could be used by physicians and health professionals to promote a quit
      attempt. 

PMID- 24577283
TI  - Do children's health resources differ according to preschool physical activity
      programmes and parental behaviour? A mixed methods study.
AB  - Preschool can have positive effects on the development of a healthy lifestyle.
      The present study analysed to what extent different conditions, structures and
      behavioural models in preschool and family-children's central social microsystems
      can lead to differences in children's health resources. Using a cross-sectional
      mixed methods approach, contrast analyses of "preschools with systematic physical
      activity programmes" versus "preschools without physical activity programmes"
      were conducted to assess the extent to which children's physical activity,
      quality of life and social behaviour differ between preschools with systematic
      and preschools without physical activity programmes. Differences in children's
      physical activity according to parental behaviour were likewise assessed. Data on
      child-related outcomes and parent-related factors were collected via parent
      questionnaires and child interviews. A qualitative focused ethnographic study was
      performed to obtain deeper insight into the quantitative survey data. Two hundred
      and twenty seven (227) children were interviewed at 21 preschools with systematic
      physical activity programmes, and 190 at 25 preschools without physical activity
      programmes. There was no significant difference in children's physical activity
      levels between the two preschool types (p = 0.709). However, the qualitative data
      showed differences in the design and quality of programmes to promote children's
      physical activity. Data triangulation revealed a strong influence of parental
      behaviour. The triangulation of methods provided comprehensive insight into the
      nature and extent of physical activity programmes in preschools and made it
      possible to capture the associations between systematic physical activity
      promotion and children's health resources in a differential manner. 

PMID- 24577284
TI  - Structure analysis of aerobic granule from a sequencing batch reactor for organic
      matter and ammonia nitrogen removal.
AB  - Aerobic granules were cultivated in a sequencing batch reactor (SBR). COD and
      ammonia nitrogen removal rate were 94% and 99%, respectively. The diameter,
      settling velocity and SVI10 of granules ranged from 2 to 5 mm, 80 to 110 m/h and
      about 40 mL/g, respectively. Freezing microtome images, DO concentration profiles
      by microelectrode, distribution of bacteria and EPS by confocal laser scanning
      microscopy (CLSM) show that the aerobic granules have a three-layer structure.
      Each layer has different thickness, character, bacteria, and DO transfer rate. A
      hypothesis for granule structure is proposed: the first layer, the surface of the
      granule, is composed mostly of heterotrophic organisms for organic matter
      removal, with a thickness range from 150 to 350 MUm; the second layer, mostly
      composed of autotrophic organisms for ammonia nitrogen removal, with a thickness
      range from 250 to 450 MUm; the third layer, located in the core of the granule,
      has mostly an inorganic composition and contains pores and channels. 

PMID- 24577285
TI  - The influence of changes in lifestyle and mercury exposure in riverine
      populations of the Madeira River (Amazon Basin) near a hydroelectric project.
AB  - In the Amazon Basin, naturally occurring methylmercury bioaccumulates in fish,
      which is a key source of protein consumed by riverine populations. The
      hydroelectric power-plant project at Santo Antonio Falls allows us to compare the
      Hg exposure of riverine populations sparsely distributed on both sides of the
      Madeira river before the area is to be flooded. From 2009 to 2011, we concluded a
      population survey of the area (N = 2,008; representing circa 80% of community
      residents) that estimated fish consumption and mercury exposure of riverine
      populations with different degrees of lifestyle related to fish consumption. Fish
      samples from the Madeira river (N = 1,615) and 110 species were analyzed for Hg.
      Hair-Hg was significantly lower (p < 0.001) in less isolated communities near to
      the capital of Porto Velho (median 2.32 ppm) than in subsistence communities in
      the Cunia Lake, 180 km from Porto Velho city (median 6.3 ppm). Fish Hg
      concentrations ranged from 0.01 to 6.06 ug/g, depending on fish size and feeding
      behavior. Currently available fish in the Madeira river show a wide variability
      in Hg concentrations. Despite cultural similarities, riparians showed hair-Hg
      distribution patterns that reflect changes in fish-eating habits driven by
      subsistence characteristics.

PMID- 24577286
TI  - Vision loss after intravitreal ocriplasmin: correlation of spectral-domain
      optical coherence tomography and electroretinography.
AB  - IMPORTANCE Clinical trials indicate that visual impairment is significantly
      greater in patients receiving ocriplasmin than placebo. The mechanism of this
      symptom has not been explained. We report a patient with persistent darkening of
      her vision after intravitreal ocriplasmin and describe ancillary testing findings
      that may yield insights into the effects of ocriplasmin and the cause of this
      symptom. OBSERVATIONS We describe a 71-year-old woman with symptomatic
      vitreomacular traction who received intravitreal ocriplasmin and experienced
      darkening of vision in dim illumination for 4 months, despite improvement in
      visual acuity and release of symptomatic vitreomacular traction. We demonstrate
      that disruption of photoreceptor inner segment-outer segment (ellipsoid) layer on
      SD-OCT and reduced ERG amplitudes correspond to the patient's symptom of darkened
      vision. The ERG demonstrated a greater reduction in scotopic function compared
      with photopic function. CONCLUSIONS AND RELEVANCE On the basis of these findings,
      it is possible that ocriplasmin may have a diffuse enzymatic effect on
      photoreceptors or the retinal pigment epithelium that is not limited to areas of
      vitreomacular adhesion. The rod photoreceptors may be more susceptible than cone
      photoreceptors to the effects of ocriplasmin. Further work is needed to
      understand mechanisms of visual impairment after ocriplasmin. 

PMID- 24577288
TI  - Fast-spiking cell to pyramidal cell connections are the most sensitive to
      propofol-induced facilitation of GABAergic currents in rat insular cortex.
AB  - BACKGROUND: Propofol facilitates gamma-aminobutyric acid-mediated inhibitory
      synaptic transmission. In the cerebral cortex, gamma-aminobutyric acidergic
      interneurons target both excitatory pyramidal cells (Pyr) and fast-spiking (FS)
      and non-FS interneurons. Therefore, the propofol-induced facilitation of
      inhibitory transmission results in a change in the balance of excitatory and
      inhibitory inputs to Pyr. However, it is still unknown how propofol modulates
      gamma-aminobutyric acidergic synaptic transmission in each combination of Pyr and
      interneurons. METHODS: The authors examined whether propofol differentially
      regulates inhibitory postsynaptic currents (IPSCs) depending on the presynaptic
      and postsynaptic cell subtypes using multiple whole cell patch clamp recording
      from gamma-aminobutyric acidergic interneurons and Pyr in rat insular cortex.
      RESULTS: Propofol (10 MUM) consistently prolonged decay kinetics of unitary IPSCs
      (uIPSCs) in all types of inhibitory connections without changing paired-pulse
      ratio of the second to first uIPSC amplitude or failure rate. The FS->Pyr
      connections exhibited greater enhancement of uIPSC charge transfer (2.2 +/- 0.5
      pC, n = 36) compared with that of FS->FS/non-FS connections (0.9 +/- 0.2 pC, n =
      37), whereas the enhancement of charge transfer in non-FS->Pyr (0.3 +/- 0.1 pC, n
      = 15) and non-FS->FS/non-FS connections (0.2 +/- 0.1 pC, n = 36) was smaller to
      those in FS->Pyr/FS/non-FS. Electrical synapses between FS pairs were not
      affected by propofol. CONCLUSIONS: The principal inhibitory connections (FS->Pyr)
      are the most sensitive to propofol-induced facilitation of uIPSCs, which is
      likely mediated by postsynaptic mechanisms. This preferential uIPSC enhancement
      in FS->Pyr connections may result in suppressed neural activities of projection
      neurons, which in turn reduces excitatory outputs from cortical local circuits.

PMID- 24577287
TI  - Computer-assisted delivery of cognitive-behavioral therapy: efficacy and
      durability of CBT4CBT among cocaine-dependent individuals maintained on
      methadone.
AB  - OBJECTIVE: A previous pilot trial evaluating computer-based training for
      cognitive-behavioral therapy (CBT4CBT) in 77 heterogeneous substance users
      (alcohol, marijuana, cocaine, and opioids) demonstrated preliminary support for
      its efficacy in the context of a community-based outpatient clinic. The authors
      conducted a more definitive trial in a larger, more homogeneous sample. METHOD:
      In this randomized clinical trial, 101 cocaine-dependent individuals maintained
      on methadone were randomly assigned to standard methadone maintenance or
      methadone maintenance with weekly access to CBT4CBT, with seven modules delivered
      within an 8-week trial. RESULTS: Treatment retention and data availability were
      high and comparable across the treatment conditions. Participants assigned to the
      CBT4CBT condition were significantly more likely to attain 3 or more consecutive
      weeks of abstinence from cocaine (36% compared with 17%; p<0.05, odds
      ratio=0.36). The group assigned to CBT4CBT also had better outcomes on most
      dimensions, including urine specimens negative for all drugs, but these reached
      statistical significance only for individuals completing the 8-week trial (N=69).
      Follow-up data collected 6 months after treatment termination were available for
      93% of the randomized sample; these data indicate continued improvement for those
      assigned to the CBT4CBT group, replicating previous findings regarding its
      durability. CONCLUSIONS: This trial replicates earlier findings indicating that
      CBT4CBT is an effective adjunct to addiction treatment with durable effects.
      CBT4CBT is an easily disseminable strategy for broadening the availability of
      CBT, even in challenging populations such as cocaine-dependent individuals
      enrolled in methadone maintenance programs.

PMID- 24577289
TI  - Doing the right thing for asymptomatic bacteriuria: knowing less leads to doing
      less.

PMID- 24577290
TI  - Reducing antimicrobial therapy for asymptomatic bacteriuria among noncatheterized
      inpatients: a proof-of-concept study.
AB  - This proof-of-concept study demonstrates that no longer routinely reporting urine
      culture results from noncatheterized medical and surgical inpatients can greatly
      reduce unnecessary antimicrobial therapy for asymptomatic bacteriuria without
      significant additional laboratory workload. Larger studies are needed to confirm
      the generalizability, safety, and sustainability of this model of care. 

PMID- 24577291
TI  - Changes in the bacterial community structure in stored wormbed leachate.
AB  - Organic wastes, such as cow manure, are often composted with earthworms
      (vermicomposting) while excess water is drained and collected. This wormbed
      leachate is nutrient-rich and it has been extensively used to fertilize plants.
      However, it is derived partially from a not yet finished compost process and
      could exhibit phytotoxicity or contain potentially hazardous microorganisms. The
      bacterial community in wormbed leachate derived from vermicomposting of cow
      manure was studied by pyrosequencing the 16S rRNA gene. The fresh wormbed
      leachate was rich in Mollicutes, particularly the genus Acholeplasma which
      contain phytopathogen species. The abundance of the Mollicutes decreased when the
      leachate was stored, while that of the Rhizobiales and the genus Pseudomonas
      increased. The bacterial communities changed rapidly in the leachate during
      storage. The changes in ammonium, nitrate and inorganic carbon content of the
      wormbed leachate when stored were correlated to changes in the bacterial
      community structure. It was found that storage of the wormbed leachate might be
      required before it can be applied to crops as large proportions of potentially
      plant pathogens were found in the fresh leachate.

PMID- 24577292
TI  - Dramatic reduction of culture time of Mycobacterium tuberculosis.
AB  - Mycobacterium tuberculosis culture, a critical technique for routine diagnosis of
      tuberculosis, takes more than two weeks. Here, step-by-step improvements in the
      protocol including a new medium, microaerophlic atmosphere or ascorbic-acid
      supplement and autofluorescence detection dramatically shortened this delay. In
      the best case, primary culture and rifampicin susceptibility testing were
      achieved in 72 hours when specimens were inoculated directly on the medium
      supplemented by antibiotic at the beginning of the culture.

PMID- 24577293
TI  - [Guideline-conform diagnostics in language impairments].
AB  - In order to distinguish more accurately and easily between language difficulties
      in need of therapy or special support versus language impairments a S2K guideline
      was developed by interdisciplinary teams of different (medical) societies and
      professional associations. This guideline was published in 2011 and has replaced
      all existing monodisciplinary guidelines. According to the new S2K guideline
      standardised measures of language testing are mandatory. Apart from reviewing the
      S2K guidelines, this article aims to suggest how these guidelines can be
      established in clinical practice. By closely following this new guideline,
      testing and diagnosing children with language difficulties is believed to be
      enhanced considerably, and also comply with quality management standards. 

PMID- 24577296
TI  - Another advantage of the transseptal suture: shortens the duration of waking up
      after anesthesia.
AB  - AIM: The aim of this study was to investigate the effects of transseptal suturing
      against 3 different types of nasal packings with respect to pain, operating time,
      and postoperative complications after nasal septal surgery. PATIENTS AND METHODS:
      Two hundred twenty-eight patients (aged between 18 and 58 y) undergoing nasal
      septal surgery were included in the study. After surgery, 4 types of nasal
      packing were used: (1) transseptal suturing (group A: 57 patients), (2) internal
      nasal splint (group B: 57 patients), (3) Merocel standard 8-cm packing without
      airway (group C: 57 patients), and (4) soft paraffin gauze dressing (group D: 57
      patients). RESULTS: Regarding the mean operating time, there was no statistically
      significant difference among groups B, C, and D (P > 0.05). However, when the
      operating times observed in the said 3 groups were compared with those observed
      in group A, the difference was statistically significant (P < 0.05). The mean
      (SD) postoperative pain score within 1 to 48 hours was 2.9 (1.3; median, 2) in
      group A, 6.3 (1.4; median, 6) in group B, 7.5 (1.1; median, 7) in group C, and
      7.7 (1.8; median, 7) in group D. Starting from the postoperative 48th hour,
      internal nasal splint, Merocel packing, and soft paraffin gauze dressing were
      significantly more painful compared with transseptal suturing (P < 0.05). When
      compared with the other groups, extubation period and postoperative care unit
      stay were shorter in the transseptal suturing group (P < 0.05). Regarding
      infection, hematoma, synechia, or perforation, there was no statistically
      significant difference among the groups (P > 0.05). CONCLUSIONS: Transseptal
      suturing technique is a useful alternative to packing, with only a minor increase
      in operating time. Particularly, transseptal suturing shortens extubation time
      and postoperative care unit stay.

PMID- 24577297
TI  - Multiple irritation fibromas after dorsum linguae biopsy.
AB  - Irritation fibroma is one of the most frequent occurrences in benign soft tissue
      growth of the oral cavity. Chronic irritation and trauma are often identified as
      the causative factors. Recently, we experienced an unusual case of multiple
      irritation fibromas that occurred in the suture points after dorsum linguae
      biopsy. To the best of our knowledge, it has not been reported. Hence, the rare
      case was described and several possible causes were discussed. 

PMID- 24577298
TI  - An unusual cause of hemoptysis: leech in the supraglottic region of the larynx.
AB  - Leeches live in fresh water and moist terrestrial environments. Most infestations
      are cutaneous. However, internal infestation occurs principally in the rural
      parts of the Mediterranean countries as well as in Africa and Asia. Thus,the
      possibility of leech endoparasitism should be kept in mind for a patient
      presenting with hemoptysis and with a history of close contact with fresh water
      in tropical countries.Human infestation is rare and usually occurs after
      consumption of contaminated water or swimming in leech-infested still waters such
      as lakes and dams.Herein, we report 2 live leech cases with hemoptysis in the
      supraglottic region of the larynx. 

PMID- 24577299
TI  - Cervical subcutaneous emphysema and pneumomediastinum after septorhinoplasty.
AB  - Cervical and facial subcutaneous emphysema is mainly caused by maxillofacial
      trauma or head and neck surgery. There are only 2 cases of subcutaneous emphysema
      after septorhinoplasty in the English literature. We report a case of
      subcutaneous emphysema and pneumomediastinum after a septorhinoplasty.A healthy
      35-year-old man with nasal obstruction and dissatisfaction with the shape of his
      nose was referred to our outpatient clinic. The patient had a septorhinoplasty
      including bilateral medial and lateral osteotomy under general anesthesia. On the
      fifth day after the surgery, the patient visited the emergency department with
      swelling and pain in the right submandibular area and cheek. On computed
      tomographic (CT) scans, air was observed in the right temporal space, masticator
      space, submandibular space, and superior mediastinal space. He was immediately
      hospitalized for administration of intravenous antibiotics and bed rest.On the
      fifth day after the hospitalization, follow-up CT scans were performed.
      Subcutaneous emphysema and pneumomediastinum were markedly decreased. The patient
      was discharged on the fifth day. 

PMID- 24577300
TI  - Orbital complication of balloon sinuplasty.
AB  - Balloon sinuplasty (BS) is a relatively new conservative approach, first licensed
      for the treatment of chronic rhinosinusitis in 2006. The philosophy of the
      technique is to improve impaired sinus drainage by enlarging stenosed or
      obstructed natural sinus ostiums. The recent improvements in balloon sinuplasty
      made virtually all paranasal sinus ostiums to be safely accessible with this
      technique. Compared to classical endoscopic technique, the main advantage of
      balloon sinuplasty is the low complication rate reported. It is very seldom to
      encounter major complications related to critical structures such as orbits and
      skull base. Since its first description, very few severe complications directly
      attributable to the technique have been reported in literature as of today. In
      this article, we report a case of medial orbital wall fracture developed due to
      the pressure of the inflated balloon in a balloon sinuplasty procedure. 

PMID- 24577301
TI  - Cheek drooping in 2 patients with maxillary fractures after rigid fixation with
      bioabsorbable mesh.
AB  - Bioabsorbable plate-screw systems are commonly used for the internal fixation of
      facial bone fractures. The anterior maxilla has a unique curved shape, and
      fractured bony fragments tend to be small and fragile; therefore, more effective
      rigid fixation can be achieved using a molded bioabsorbable mesh rather than a
      bioabsorbable plate. Herein, we describe 2 patients with cheek drooping after a
      rigid fixation of comminuted maxillary fracture using bioabsorbable meshes and
      screws.The postoperative courses were uneventful, but both showed soft tissue
      bulging in the cheek area of the operation site for 12 to 13 months after the
      operation. No other symptom or sign related to inflammation or foreign body
      reaction was noted.In comminuted maxillary fractures, bone fragments are more
      conveniently fixed with a 1-piece molded bioabsorbable mesh. However, it is
      believed that a single large mesh may interfere with adhesion between the
      maxillary surface and the overlying soft tissue. Therefore, we recommend using
      the least amount of mesh to fixate maxillary bone fragments. 

PMID- 24577302
TI  - Assessing long-term outcomes of open and endoscopic sagittal synostosis
      reconstruction using three-dimensional photography.
AB  - Sagittal synostosis has been successfully managed with numerous surgical
      techniques. Nevertheless, few data on long-term outcomes exist to justify use of
      one surgical technique over another. In this study, we compared children with
      surgically corrected sagittal synostosis to their age-matched control subjects to
      assess the longevity of their corrections. Furthermore, the outcomes of open
      repairs were compared with endoscopic repairs.Following institutional review
      board approval, three-dimensional photographs of patients who underwent surgical
      reconstruction for nonsyndromic sagittal synostosis were analyzed to determine
      biparietal and anterior-posterior diameter, circumference, cephalic index,
      cranial vault volume, cranial height, and forehead inclination. Thirteen patients
      who had undergone open repair, including 6 total cranial vault and 7 modified-pi
      reconstructions, and 6 patients who had undergone endoscopic strip craniectomy
      with barrel-stave osteotomies and postoperative helmeting were compared with
      nonsynostotic age-matched control subjects. Mean follow-up was 97.5 months after
      open and 48.9 months after endoscopic repair. Student t tests were used for
      analysis. In the second arm of this study, 33 patients who had undergone
      endoscopic repair were compared with the 13 patients who had undergone open
      repair; mean follow-up was 24.8 months after endoscopic repair. Linear regression
      models were used to adjust for age and sex.After comparing three-dimensional
      photographs of children who were more than 3 years postoperative from surgical
      correction for sagittal synostosis with their age-matched control subjects, no
      statistically significant differences were found in any of the measured
      parameters. In addition, no differences were detected between open reconstruction
      versus endoscopic repair, suggesting equivalence in final results for both
      procedures. 

PMID- 24577303
TI  - Le Fort I osteotomy combined with endoscopic assistance for treatment of compound
      fracture of maxilla, zygoma, and orbital floor.
AB  - PURPOSE: The traditional surgery to reconstruct the compound fracture of the
      zygoma, maxilla, and orbital floor was usually open reduction and internal
      fixation using miniplate, and surgeons now can perform the endoscopic repair of
      relatively simple zygoma or orbital blowout fracture. In this study, we try to
      reconstruct midfacial complex fracture by combined application of intraoral
      approach and endoscopic-assisted minimally invasive method. METHODS: Six patients
      with traumatic midfacial fracture, including maxilla, zygoma, and orbital floor
      fracture, were selected. Intraoral Le Fort I osteotomy approach and endoscopic
      assisted minimally invasive method were combined and applied to treat this
      complex midfacial fracture. RESULTS: The intraoral incision combined with
      endoscope offered suitable approach for reduction and fixation of fractured
      zygoma. The Le Fort I osteotomy could help to effectively reduce the fractured
      maxilla and offered useful operative approach for endoscope. The endoscope
      combined with a balloon catheter could successfully reconstruct the orbital floor
      fracture, and no intraoperative complications were encountered. The balloon
      catheter was removed 4 to 8 weeks after operation and did not lead to infection
      and obviously disrupt the healing of bone segments. The postoperative eye and
      occlusion function, evaluated by clinical examination, was satisfactory at 3
      months. CONCLUSIONS: Although there are some limitations and strict indications,
      the advantages of this method may offer alternative choice for reconstruction of
      compound midfacial fracture.

PMID- 24577304
TI  - New palatal distraction device by both bone-borne and tooth-borne force
      application in a paramedian bone anchorage site: surgical and occlusal
      considerations on clinical cases.
AB  - Maxillary constriction is a very common pathology with implications on dental
      occlusion, temporomandibular joint dysfunction, nasal breathing, and impairment
      on the smile and face esthetic.New techniques for expansion of the maxillary
      bones are particularly useful in relation to the new esthetic ideals of smile and
      face beauty.To achieve a bodily expansion of the maxillary bones, we developed a
      new rigid palatal distractor device with both tooth-borne and paramedian bone
      borne anchorages to achieve a safe and simple anchorage site suitable also for
      orthodontic appliances.The reported cases show good results, with bodily
      maxillary expansion and cross-bite correction without any problems or
      complications. Substantial advantages of this new device and technique, in
      comparison with other commonly used palatal distractors, consisting of bodily
      maxillary movements, avoidance of relapse risks, and safe and simple screw
      insertion site for bone anchorage also suitable for orthodontic movements, are
      discussed. 

PMID- 24577305
TI  - Metopic frontal suture in a patient with severe dentofacial deformity undergoing
      bimaxillary surgery.
AB  - Six cranial fontanelles are present in newborns along with cranial sutures.
      Cranial sutures are a synarthrosis type of joints that occur in the skull after
      closure of fontanelles. Because of ossification up to 24 months, all fontanelles
      should be closed. Normal frontal bone consists of only frontonasal,
      frontozygomatic, frontomaxillaris, frontolacrimalis, and main coronal sutures.
      Metopic frontal suture occurs very rarely in adults. Some metopic frontal sutures
      might be related to genetic or general disorders or perhaps are related to an
      improper ossification. In some cases, it persists as a complete suture extending
      from the nasion to the anterior angle of the bregma, and this condition is called
      metopism, or metopic suture. In this article, we present a patient with metopic
      frontal suture diagnosed accidentally during preparation for bimaxillary
      orthognathic surgery. 

PMID- 24577307
TI  - Modified dovetail-plasty in scar revision.
AB  - Scar revision is one of the fundamental techniques in the field of plastic and
      reconstructive surgery. Local flaps, such as a Z-plasty, W-plasty, or geometric
      broken-line closure, have been used for scar revision. Camouflaging a scar during
      scar revision for marginal scars from skin grafts and flaps, trapdoor scars, and
      linear scars is difficult. We describe our experience with the use of modified
      dovetail-plasty for scar revision in these difficult areas. Our study group
      consisted of 28 cases among 22 patients (9 males and 13 females) with a mean age
      of 33.6 years (range, 6-61 years). The conspicuous scars were located on the face
      (50%) and extremities (50%). The authors designed Y-shaped incision lines to
      relax the skin tension lines on one side of the excision line and trapezoid
      incision lines on the other side. There were 16 follow-up operations performed
      over 6 months after the initial operation among a total of 22 patients. There
      were scar depressions (2 patients) and a hypertrophic scar (1 patient) at the
      interval area between the dovetail flaps. A diffuse hypertrophic scar occurred in
      1 patient with a dorsal foot scar. The overall success rates of the procedure as
      assessed by the surgeons were as follows: excellent (75%), good (12.4%), fair
      (6.3%), and poor (6.3%). This new local flap can achieve an inconspicuous scar
      using a blurred scar line and reducing tension. The authors recommend a modified
      dovetail-plasty for the revision of trapdoor scars and scars under excessive
      tension. 

PMID- 24577306
TI  - Comparison of the osteogenic potential of OsteoSelect demineralized bone matrix
      putty to NovaBone calcium-phosphosilicate synthetic putty in a cranial defect
      model.
AB  - The purpose of this study was to compare the osteogenic potential of a synthetic
      and a demineralized bone matrix (DBM) putty using a cranial defect model in New
      Zealand white rabbits. Paired, bilateral critical-size defects (10 mm) were
      prepared in the frontal bones of 12 rabbits and filled with either OsteoSelect
      DBM Putty or NovaBone calcium-phosphosilicate putty. At days 43 and 91, 6 rabbits
      were killed and examined via semiquantitative histology and quantitative
      histomorphometry. Defects filled with the DBM putty were histologically
      associated with less inflammation and fibrous tissue in the defect and more new
      bone than the synthetic counterpart at both time points. Histomorphometric
      analysis revealed that the defects filled with DBM putty were associated with
      significantly more bone formation at day 43 (70.7% vs 40.7%, P = 0.043) and at
      day 91 (70.4% vs 39.9%, P = 0.0044). The amount of residual implant was similar
      for both test groups at each time point. 

PMID- 24577308
TI  - An exploratory analysis of the factor structure of the Dysfunctional Attitude
      Scale-Form A (DAS).
AB  - A number of studies have attempted to identify the factor structure of the
      Dysfunctional Attitude Scale (DAS). However, no studies have done so using a
      clinical sample of outpatients likely to generalize to the clinical trials in
      which the DAS is commonly used. The current investigation utilized exploratory
      structural equation modeling in an outpatient sample (N = 982) and found support
      for a one-factor solution (composed of 19 items). This solution was largely
      confirmed in a second outpatient sample (N = 301). Construct validity was
      demonstrated in correlations with measures of depression, social interaction
      anxiety, and symptoms of obsessive-compulsive disorder. 

PMID- 24577309
TI  - Development and evaluation of an online, multicomponent working memory battery.
AB  - Research has demonstrated strong connections among working memory (WM), higher
      level cognition, and academic achievement. Despite the importance of WM,
      currently available WM tests have practical limitations and lack comprehensive
      coverage of multiple WM components. The Working Memory Battery (WOMBAT) includes
      nine subtests measuring multiple content domains and processing demands, in
      accordance with contemporary WM theoretical frameworks. The current study
      evaluated the WOMBAT factor structure and identified misfitting items using
      confirmatory factor analysis and Rasch modeling with scores from 125 adolescents
      and 177 adults (N = 302). Overall, results indicated the WOMBAT measures separate
      Verbal, Static Visual-Spatial, and Dynamic Visual-Spatial dimensions, and that
      more than 98% of items contribute to measurement of those dimensions. This
      provides support for the theoretical organization of WM into three distinct
      content domains in the WOMBAT. Misfitting items were identified using infit and
      outfit indices for further review to improve reliability and stability. Results
      also demonstrated adequate person separation and Rasch person reliability and
      item reliability. Test-retest reliability and internal consistency coefficients
      suggest adequate reliability for early-stage research, but further refinement is
      needed before the WOMBAT can be used for individual decision making. Implications
      for future test development and research on the WM construct are provided.

PMID- 24577310
TI  - Development of abbreviated eight-item form of the Penn Verbal Reasoning Test.
AB  - The ability to reason with language is a highly valued cognitive capacity that
      correlates with IQ measures and is sensitive to damage in language areas. The
      Penn Verbal Reasoning Test (PVRT) is a 29-item computerized test for measuring
      abstract analogical reasoning abilities using language. The full test can take
      over half an hour to administer, which limits its applicability in large-scale
      studies. We previously described a procedure for abbreviating a clinical rating
      scale and a modified procedure for reducing tests with a large number of items.
      Here we describe the application of the modified method to reducing the number of
      items in the PVRT to a parsimonious subset of items that accurately predicts the
      total score. As in our previous reduction studies, a split sample is used for
      model fitting and validation, with cross-validation to verify results. We find
      that an 8-item scale predicts the total 29-item score well, achieving a
      correlation of .9145 for the reduced form for the model fitting sample and .8952
      for the validation sample. The results indicate that a drastically abbreviated
      version, which cuts administration time by more than 70%, can be safely
      administered as a predictor of PVRT performance. 

PMID- 24577311
TI  - Purification and characterization of aporphine alkaloids from leaves of Nelumbo
      nucifera Gaertn and their effects on glucose consumption in 3T3-L1 adipocytes.
AB  - Aporphine alkaloids from the leaves of Nelumbo nucifera Gaertn are substances of
      great interest because of their important pharmacological activities,
      particularly anti-diabetic, anti-obesity, anti-hyperlipidemic, anti-oxidant, and
      anti-HIV's activities. In order to produce large amounts of pure alkaloid for
      research purposes, a novel method using high-speed counter-current chromatography
      (HSCCC) was developed. Without any initial cleanup steps, four main aporphine
      alkaloids, including 2-hydroxy-1-methoxyaporphine, pronuciferine, nuciferine and
      roemerine were successfully purified from the crude extract by HSCCC in one step.
      The separation was performed with a simple two-phase solvent system composed of n
      hexane-ethyl acetate-methanol-acetonitrile-water (5:3:3:2.5:5, v/v/v/v/v). In
      each operation, 100 mg crude extracts was separated and yielded 6.3 mg of 2
      hydroxy-1-methoxyaporphine (95.1% purity), 1.1 mg of pronuciferine (96.8%
      purity), 8.5 mg of nuciferine (98.9% purity), and 2.7 mg of roemerine (97.4%)
      respectively. The chemical structure of four aporphine alkaloids are identified
      by means of electrospray ionization MS (ESI-MS) and nuclear magnetic resonance
      (NMR) analysis. Moreover, the effects of four separated aporphine alkaloids on
      insulin-stimulated glucose consumption were examined in 3T3-L1 adipocytes. The
      results showed that 2-hydroxy-1-methoxyaporphine and pronuciferine increased the
      glucose consumption significantly as rosiglitazone did.

PMID- 24577312
TI  - PseAAC-General: fast building various modes of general form of Chou's pseudo
      amino acid composition for large-scale protein datasets.
AB  - The general form pseudo-amino acid composition (PseAAC) has been widely used to
      represent protein sequences in predicting protein structural and functional
      attributes. We developed the program PseAAC-General to generate various different
      modes of Chou's general PseAAC, such as the gene ontology mode, the functional
      domain mode, and the sequential evolution mode. This program allows the users to
      define their own desired modes. In every mode, 544 physicochemical properties of
      the amino acids are available for choosing. The computing efficiency is at least
      100 times that of existing programs, which makes it able to facilitate the
      extensive studies on proteins and peptides. The PseAAC-General is freely
      available via SourceForge. It runs on both Linux and Windows. 

PMID- 24577313
TI  - HBx protein promotes oval cell proliferation by up-regulation of cyclin D1 via
      activation of the MEK/ERK and PI3K/Akt pathways.
AB  - Growing evidence has shown that hepatic oval cells, also named liver progenitor
      cells, play an important role in the process of liver regeneration in various
      liver diseases. Oval cell proliferation has been reported in hepatitis B virus
      (HBV)-associated hepatocellular carcinoma (HCC) and chronic liver disease.
      Studies have found expression of HBV surface and core antigens in oval cells in
      the livers of patients with HCC, suggesting that HBV infection of oval cells
      could be a mechanism of human hepatocarcinogenesis. In addition, there is
      evidence of multiplication of HBV in oval cell culture. However, little research
      has been performed to explore the role of HBV-encoded proteins in the
      proliferation of hepatic oval cells. Previously, we successfully transfected the
      HBV x (HBx) gene, one of the four genes in the HBV genome, into a rat LE/6 oval
      cell line. In this study, we tested whether or not the transfected HBx gene could
      affect oval cell proliferation in vitro. Our results show that overexpression of
      HBx promotes the proliferation of oval cells and increases cyclin D1 expression,
      assessed at both the mRNA and protein levels. We also found that HBx activated
      the PI-3K/Akt and MEK/ERK1/2 pathways in HBx-transfected oval cells. Furthermore,
      the HBx-induced increases in cyclin D1 expression and oval cell proliferation
      were completely abolished by treatment with either MEK inhibitor PD184352 or PI
      3K inhibitor LY294002. These results demonstrated that HBx has the ability to
      promote oval cell proliferation in vitro, and its stimulatory effects on cell
      proliferation and expression of cyclin D1 depend on the activation of the MEK/ERK
      and PI3K/Akt signaling pathways in cultured oval cells.

PMID- 24577314
TI  - Docetaxel-loaded chitosan microspheres as a lung targeted drug delivery system:
      in vitro and in vivo evaluation.
AB  - The aim of this study was to prepare docetaxel-loaded chitosan microspheres and
      to evaluate their in vitro and in vivo characteristics. Glutaraldehyde
      crosslinked microspheres were prepared using a water-in-oil emulsification
      method, and characterized in terms of the morphological examination, particle
      size distribution, encapsulation ratio, drug-loading coefficient and in vitro
      release. Pharmacokinetics and biodistribution studies were used to evaluate that
      microspheres have more advantage than the conventional formulations. The emulsion
      crosslinking method was simple to prepare microspheres and easy to scale up. The
      formed microspheres were spherical in shape, with a smooth surface and the size
      was uniform (9.6 +/- 0.8 um); the encapsulation efficiency and drug loading of
      prepared microspheres were 88.1% +/- 3.5% and 18.7% +/- 1.2%, respectively. In
      vitro release indicated that the DTX microspheres had a well-sustained release
      efficacy and in vivo studies showed that the microspheres were found to release
      the drug to a maximum extent in the target tissue (lung). The prepared
      microspheres were found to possess suitable physico-chemical properties and the
      particle size range. The sustained release of DTX from microspheres revealed its
      applicability as drug delivery system to minimize the exposure of healthy tissues
      while increasing the accumulation of therapeutic drug in target sites. 

PMID- 24577315
TI  - Notes on the epidemiology of multiple sclerosis, with special reference to
      dietary habits.
AB  - A hypothesis, based primarily on the occurrence of multiple sclerosis (MS) in the
      Faroe Islands and supported by numerous analytical epidemiological studies, is
      described. It proposes that MS is caused by the interaction of a virus disease
      with intestinal pathology, e.g., infectious mononucleosis, and application of
      smoked and nitrate/nitrite-cured meat products in the diet during circumscribed
      time intervals. The biological mechanisms might involve a break of tolerance by
      an alteration of self within the central nervous system, by nitrophenylated
      compounds conjugated to animal tissue, in particular to proteins occurring in the
      central nervous system. Further research is needed. 

PMID- 24577316
TI  - Association between single nucleotide polymorphism rs1044925 and the risk of
      coronary artery disease and ischemic stroke.
AB  - The present study was performed to clarify the association between the acyl
      CoA:cholesterol acyltransferase-1 (ACAT-1) single nucleotide polymorphism (SNP)
      rs1044925 and the risk of coronary artery disease (CAD) and ischemic stroke (IS)
      in the Guangxi Han population. Polymerase chain reaction and restriction fragment
      length polymorphism was performed to determine the genotypes of the ACAT-1 SNP
      rs1044925 in 1730 unrelated subjects (CAD, 587; IS, 555; and healthy controls;
      588). The genotypic and allelic frequencies of rs1044925 were significantly
      different between the CAD patients and controls (p = 0.015) and borderline
      different between the IS patients and controls (p = 0.05). The AC/CC genotypes
      and C allele were associated with a decreased risk of CAD and IS (CAD: p = 0.014
      for AC/CC vs. AA, p = 0.022 for C vs. A; IS: p = 0.014 for AC/CC vs. AA; p =
      0.017 for C vs. A). The AC/CC genotypes in the healthy controls, but not in CAD
      or IS patients, were associated with an increased serum high-density lipoprotein
      cholesterol (HDL-C) concentration. The present study shows that the C allele
      carriers of ACAT-1 rs1044925 were associated with an increased serum HDL-C level
      in the healthy controls and decreased risk in CAD and IS patients. 

PMID- 24577318
TI  - Echocardiography-derived tricuspid regurgitant jet velocity is an important
      marker for the progression of sickle-cell disease.
AB  - BACKGROUND: Although echocardiography-derived tricuspid regurgitant jet velocity
      (TRV) is associated with increased mortality in sickle-cell disease (SCD), it is
      unclear whether increased TRV is a marker of multiorgan disease due to systemic
      vasculopathy or related to increased pulmonary artery systolic pressure with
      episodes of multiple acute chest syndrome (ACS). METHODS: Our study analyzed 148
      consecutive patients with transthoracic echocardiography with TRV data, who came
      to our adult SCD Clinic at the Wake Forest Baptist Medical Center. For our
      analysis, we took TRV >= 2.5 m/s as elevated. Patients were followed on average
      for 9 years. RESULTS: TRV >= 3 m/s was significantly associated with increased
      mortality (p < 0.001), thromboembolism (p < 0.001), hospitalization for ACS (p <
      0.001), supraventricular arrhythmia (p = 0.028), right ventricular (RV) dilation,
      decreased hemoglobin and increased creatinine. Patients with a progressive
      increase in TRV during follow-up had increased mortality (36.7 vs. 8.6%, p =
      0.007) and increased ACS (45 vs. 5.7%, p < 0.001). Death was independently
      associated with TRV >= 3 m/s (p = 0.023), ACS (p = 0.001) and increased RV basal
      diameter (p = 0.003). CONCLUSIONS: TRV is an important global marker for the
      severity and progression of SCD, and carries a significant prognostic
      implication.

PMID- 24577319
TI  - Cochlear implantation with round window insertion in children with otitis media
      with effusion.
AB  - AIMS: To discuss indications and surgical techniques for cochlear implantation
      (CI) in children with profound sensorineural hearing loss and otitis media with
      effusion (OME). METHODS: Between January 2003 and May 2013, a total of 550
      patients received cochlear implants at the Anhui Provincial Hospital, Hefei,
      China. Of these, 30 children with OME underwent CI with round window insertion in
      one stage. RESULTS: One-stage operations of CI with round window insertion were
      carried out in 30 children with OME. All electrodes were implanted successfully.
      CI was performed without complications and the electrode arrays were protected
      well. All implant devices worked normally and all patients performed well during
      an average follow-up period of 12 months. None of the patients experienced any
      immediate or delayed postoperative infection-related complications. CONCLUSIONS:
      CI with round window insertion could be safely and effectively performed in one
      stage in children with profound sensorineural hearing loss and OME. It is
      unnecessary to delay implantation to control OME, but it remains a challenging
      problem in operation.

PMID- 24577323
TI  - Temperature-dependent upconversion luminescence and dynamics of NaYF4:Yb3+/Er3+
      nanocrystals: influence of particle size and crystalline phase.
AB  - Oleic acid-capped NaYF4:Yb(3+)/Er(3+) upconversion nanocrystals (UCNCs) with
      different sizes and crystalline phases were prepared, and their temperature
      dependent upconversion luminescence (UCL) and dynamics were studied. It is
      interesting to observe that the temperature-dependent behavior of UCL for the
      beta-phase (25 nm, 45 nm and bulk) and alpha-phase (<10 nm) UCNCs is quite
      different. The UCL intensity of Er(3+) ions of the beta-phase NaYF4 demonstrates
      a maximum around 100 K, while the intensity of the alpha-phase quenches
      monotonously with elevated temperature (10-400 K). The intensity ratio of
      (2)H11/2-(4)I15/2 to (4)S3/2-(4)I15/2, RHS, increases solely with temperature for
      beta-phase NaYF4, while for the alpha-phase sample, it demonstrates a complex and
      indeterminate variation as a function of temperature. In the beta-phase samples,
      rising processes were observed in the dynamics of Er(3+) ions, while in the alpha
      phase sample, no rising process was observed and the decay processes of Er(3+)
      ions were bi-exponential. The rationale for these different temperature-dependent
      UCL properties was explained carefully. 

PMID- 24577317
TI  - Alarmin high-mobility group B1 (HMGB1) is regulated in human adipocytes in
      insulin resistance and influences insulin secretion in beta-cells.
AB  - BACKGROUND: The nuclear protein high-mobility group box 1 (HMGB1) can be
      passively released by necrotic cells or secreted actively by several cell types
      to regulate immune and inflammatory responses, as well as tissue remodeling. We
      herein aimed to characterize the effect of insulin resistance on HMGB1 in adipose
      tissue and to examine its potential role as a metabolic regulator in beta
      pancreatic cells. DESIGN: Plasma HMGB1 concentration and adipose HMGB1 expression
      were assessed in relation to obesity and insulin resistance. Cultured adipocytes
      from lean and obese patients were used to investigate the intracellular
      distribution and factors regulating HMGB1 release, as well as to test its effects
      on adipogenesis and lipid metabolism. A regulatory role for HMGB1 in insulin
      secretion was also investigated. RESULTS: Circulating HMGB1 was positively
      associated with body mass index, while adipose HMGB1 mRNA levels correlated with
      the expression of inflammatory markers. Insulin resistance modified the
      intracellular distribution of HMGB1 in human adipocytes, with HMGB1 being
      predominantly nuclear in lean and obese normoglycemic individuals while localized
      to the cytosol in obese patients with type 2 diabetes. Adipocytes from lean
      individuals exposed to conditioned media from lipopolysaccharide-stimulated
      macrophages induced HMGB1 redistribution to the cytoplasm and release. HMGB1
      treatment had no effect on differentiation and lipid metabolism in adipocytes.
      However, HMGB1, whose circulating levels correlated with postload insulin
      concentration, increased both insulin release and intracellular Ca(2+)
      concentration in INS-1 cells. CONCLUSIONS: These findings show, for the first
      time, that HMGB1 expression and release by human adipocytes is altered by
      inflammatory conditions as those imposed by obesity and insulin resistance. Our
      data reveal a novel role for HMGB1 as a stimulatory factor of insulin secretion
      of beta-pancreatic cells.

PMID- 24577324
TI  - CONSORT adherence in journals is still far from perfect.

PMID- 24577320
TI  - Changes in intensity of serotonin syndrome caused by adverse interaction between
      monoamine oxidase inhibitors and serotonin reuptake blockers.
AB  - Drug interaction between inhibitors of monoamine oxidase (MAOIs) and selective
      serotonin (5-hydroxytryptamine, 5-HT) reuptake (SSRIs) induces serotonin
      syndrome, which is usually mild but occasionally severe in intensity. However,
      little is known about neural mechanisms responsible for the syndrome induction
      and intensification. In this study, we hypothesized that the syndrome induction
      and intensity utilize two different but inter-related mechanisms. Serotonin
      syndrome is elicited by excessive 5-HT in the brain (presynaptic mechanism),
      whereas syndrome intensity is attributed to neural circuits involving 5-HT2A and
      NMDA receptors (postsynaptic mechanism). To test this hypothesis, basal 5-HT
      efflux and postsynaptic circuits were pharmacologically altered in rats by once
      daily pretreatment of the MAOI clorgyline for 3, 6, or 13 days. Syndrome
      intensity was estimated by measuring 5-HT efflux, neuromuscular activity, and
      body-core temperature in response to challenge injection of clorgyline combined
      with the SSRI paroxetine. Results showed that the onset of serotonin syndrome is
      caused by 5-HT efflux exceeding 10-fold above baseline, confirming the
      presynaptic hypothesis. The neuromuscular and body-core temperature
      abnormalities, which were otherwise mild in drug-naive rats, were significantly
      intensified to a severe level in rats pretreated with daily clorgyline for 3 and
      6 days but not in rats pretreated for 13 days. The intensified effect was blocked
      by M100907 and MK-801, suggesting that variation in syndrome intensity was
      mediated through a 5-HT2A and NMDA receptor-engaged circuit. Therefore, we
      concluded that pretreatments of MAOI pharmacologically alter the activity of
      postsynaptic circuits, which is responsible for changes in syndrome intensity. 

PMID- 24577325
TI  - Slower Walking Speed Forecasts Increased Postoperative Morbidity and 1-Year
      Mortality Across Surgical Specialties.

PMID- 24577326
TI  - Classification of the severity of acute pancreatitis: how much is really needed
      for a new classification?

PMID- 24577327
TI  - Is There No Significant Difference in the Incidence of Anastomotic Leakage
      Between the Hand-sewn and Mechanical Esophagogastric Anastomosis?

PMID- 24577328
TI  - Reply to Letter: "Outpatient Versus Hospitalization Management for Uncomplicated
      Diverticulitis".

PMID- 24577329
TI  - Molecular analysis of a series of Israeli families with Comel-Netherton syndrome.
AB  - BACKGROUND: Comel-Netherton syndrome is a rare congenital autosomal recessive
      disorder characterized by congenital ichthyosis, hair shaft abnormalities and
      atopic diathesis. It is caused by mutations in SPINK5, which encodes the serine
      protease inhibitor LEKTI. OBJECTIVES: To delineate the spectrum of mutations
      carried by a series of Israeli patients in an attempt to establish an effective
      diagnostic strategy for this disease in Israel. METHODS: Mutations were
      identified by direct sequencing of the entire coding sequence of SPINK5 and
      confirmed using polymerase chain reaction-restriction fragment length
      polymorphism. RESULTS: Three mutations were identified in seven families, of
      which two were novel. All mutations were predicted to result in premature
      termination of protein translation. CONCLUSIONS: This report presents the first
      case series of patients affected with Comel-Netherton syndrome in Israel and
      suggests that some mutations reoccur in a substantial portion of cases in our
      country, a fact that should be taken into consideration when designing molecular
      analysis in new cases.

PMID- 24577330
TI  - An optimized lead system for long-term esophageal electrocardiography.
AB  - Long-term electrocardiography (ECG) featuring adequate atrial and ventricular
      signal quality is highly desirable. Routinely used surface leads are limited in
      atrial signal sensitivity and recording capability impeding complete ECG
      delineation, i.e. in the presence of supraventricular arrhythmias. Long-term
      esophageal ECG might overcome these limitations but requires a dedicated lead
      system and recorder design. To this end, we analysed multiple-lead esophageal
      ECGs with respect to signal quality by describing the ECG waves as a function of
      the insertion level, interelectrode distance, electrode shape and amplifier's
      input range. The results derived from clinical data show that two bipolar
      esophageal leads, an atrial lead with short (15 mm) interelectrode distance and a
      ventricular lead with long (80 mm) interelectrode distance provide non-inferior
      ventricular signal strength and superior atrial signal strength compared to
      standard surface lead II. High atrial signal slope in particular is observed with
      the atrial esophageal lead. The proposed esophageal lead system in combination
      with an increased recorder input range of +/-20 mV minimizes signal loss due to
      excessive electrode motion typically observed in esophageal ECGs. The design
      proposal might help to standardize long-term esophageal ECG registrations and
      facilitate novel ECG classification systems based on the independent detection of
      ventricular and atrial electrical activity.

PMID- 24577331
TI  - Marijuana and adolescence: what can we learn from primates?

PMID- 24577332
TI  - Safety and complications of ocriplasmin: ocriplasmin, ocriplasmin; oh, how safe
      art thou?

PMID- 24577334
TI  - Comments on recent advances and recommendations for the assessment of
      autoantibodies to cellular antigens referred as antinuclear antibodies.

PMID- 24577333
TI  - Response to: 'When is it not ethical to withhold treatment for rheumatoid
      arthritis?' by Dr Yusuf Yazici.

PMID- 24577335
TI  - Response to: 'The influence of inflammation in the development of subclinical
      atherosclerosis in psoriatic arthritis' by Gonzalez-Gay et al.

PMID- 24577336
TI  - Role of peroxide ions in formation of graphene nanosheets by electrochemical
      exfoliation of graphite.
AB  - This study demonstrates a facile, mild and environmentally-friendly sustainable
      (soft processing) approach for the efficient electrochemical exfoliation of
      graphite using a sodium hydroxide/hydrogen peroxide/water (NaOH/H2O2/H2O) system
      that can produce high-quality, anodic few-layer graphene nanosheets in 95% yield
      at ambient reaction conditions. The control experiment conducted using NaOH/H2O
      revealed the crucial role of H2O2 in the exfoliation of graphite. A possible
      exfoliation mechanism is proposed. The reaction of H2O2 with hydroxyl ions (HO(
      )) leads to the formation of highly nucleophilic peroxide ions (O2(2-)), which
      play a crucial role in the exfoliation of graphite via electrochemical-potential
      assisted intercalation and strong expansion of graphite sheets. 

PMID- 24577338
TI  - The times are a-changing.

PMID- 24577339
TI  - Experimental murine acremoniosis: an emerging opportunistic human infection.
AB  - Acremonium is an emerging fungal pathogen causing severe infections. We evaluated
      the virulence of three clinically relevant species within the genus, i.e.,
      Acremonium kiliense (currently Sarocladium kiliense), Acremonium sclerotigenum-A.
      egyptiacum complex and Acremonium implicatum in a murine model of disseminated
      infection. Both immunocompetent and immunosuppresssed mice were infected with two
      inocula concentrations (2 * 10(6) and 2 * 10(8) conidia/animal) of two strains of
      each species. Tissue burden, mortality rate, histopathology and levels of (1->3)
      beta-D-glucan were used as virulence markers. None of the species of Acremonium
      tested was able to cause infection in immunocompetent mice. Conversely, severe
      infections were produced in immunocompromised mice, the spleen being the most
      affected organ. In general, the virulence of the Acremonium species tested was
      low, S. kiliense being the most virulent species.

PMID- 24577340
TI  - Removal characteristics and total dialysate content of glutamine and other amino
      acids in critically ill patients with acute kidney injury undergoing extended
      dialysis.
AB  - BACKGROUND: Acute kidney injury in critically ill patients is associated with the
      activation of protein catabolism and a negative nitrogen balance. Renal
      replacement therapy (RRT) aggravates this problem by eliminating a substantial
      amount of amino acids. However, there is scarce data on the removal
      characteristics of modern dialysis membranes in extended dialysis. METHODS: This
      is a prospective study in 10 extended dialysis sessions using a 1.8-m(2)
      polysulfone membrane (EMiC2 dialyzer or AV 1000S; FMC, Germany). Blood samples
      for 19 amino acids were drawn before, during, and after 10 h of extended dialysis
      (blood/dialysate flow 150 ml/min). In addition, samples for the calculation of
      dialyzer clearance and samples from the total spent dialysate were measured using
      a Biochrom 30 amino acid analyzer. RESULTS: Despite no significant difference in
      pre- and postdialysis plasma amino acid levels, we found an impressive amount of
      amino acids in collected spent dialysate, i.e. 10.5 g/10 h of treatment. The
      dialyzer clearance ranged from 67.6 ml/min for phenylalanine to 140.0 ml/min for
      valine. The total eliminated masses of the measured amino acids had equal values
      for both membranes. There was a significant difference between the dialyzer
      clearance of the investigated membranes for glutamine (AV 1000S: 83.3 ml/min vs.
      EMiC2: 92.0 ml/min, p = 0.02) and serine (88.8 ml/min vs. 91.8 ml/min, p =
      0.005). DISCUSSION: Our data indicate that the modern forms of RRT eliminate
      amino acids to an extent that has not been met by our nutritional support
      standards. Especially the removal of glutamine, important for immune function and
      cell regeneration, might have detrimental effects on the recovery of critically
      ill patients.

PMID- 24577341
TI  - [Chronic obstructive pulmonary disease (COPD). Current concepts and new
      therapeutic options].
AB  - Chronic obstructive pulmonary disease (COPD) is a very common chronic disease
      with increasing prevalence. Inhaled particles and gases (in particular tobacco
      smoke) induce chronic inflammation of the airways accompanied by a not fully
      reversible airflow limitation. Destruction of lung tissue and deterioration of
      gas exchange may follow. In parallel, several comorbidities can be observed. The
      COPD assessment was revised and now takes into account lung function, the
      patients' symptoms, and history of exacerbations. More recently, several new long
      acting bronchodilators received approval. Combination products, consisting of
      long-acting beta2-agonists and long-acting anticholinergics, and a new
      combination of a long-acting beta-agonist and an inhaled corticosteroid will
      follow in the near future. Smoking cessation is of central importance.

PMID- 24577342
TI  - [New drugs in rheumatology].
AB  - Because the development of a novel drug or therapeutic strategy can be monitored
      using the respective databases such as clinicaltrials.gov, true surprises in the
      field of therapeutic advances have become a very rare event. On the other hand,
      owing to the common variability of the individual entities and the large number
      of rare diseases within rheumatology and clinical immunology, introducing a novel
      drug is a very challenging task. This problem also applies specifically to the
      first phase after approval, as the usually strict in- and exclusion criteria of a
      clinical trial only match a small portion of the population with the target
      disease. Therefore, the numerous novel treatments that have been or are about to
      be introduced into clinical rheumatology are more than welcome. Key examples are
      rituximab for ANCA-associated vasculitides, ustekinumab for psoriatic arthritis,
      or interleukin-1 inhibitors for complicated gout--with more to come including a
      large group of intracellular kinase or extracellular macrophage inhibitors.

PMID- 24577343
TI  - [Development and implementation of an integrated care pathway at the POLIKUM
      health centers using the example of anemia].
AB  - BACKGROUND: Integrated treatment pathways are an appropriate means for increasing
      the quality of treatment and outcome via process optimization. Taking the POLIKUM
      Health Centers as an example, we intend to demonstrate how the implementation can
      be effected for the indication of anemia. METHOD: The development and
      implementation were executed by an interdisciplinary workgroup in several
      workshops. In addition, the diagnoses and hemoglobin values of all patients with
      requests for hemograms were obtained and analyzed at two locations. RESULTS:
      Developing the pathway required significantly greater efforts than initially
      planned. The biggest challenge was to adequately map the complexity of the
      different forms of anemia and, concomitantly, to design a pathway that can
      actually be realized in everyday life. Moreover, evaluation of the patient data
      demonstrated that there are a large number of cases where existing anemias are
      not reflected in the respective diagnoses. CONCLUSION: While the ultimate effects
      of the new pathway cannot yet be assessed conclusively, it was possible to obtain
      valuable findings for practical use even at this point. Despite the limitations
      of the sample, the surprisingly high number of undetected anemias should give
      physicians cause for taking diagnostic measures even in patients with mild
      anemia.

PMID- 24577344
TI  - Assessment of myocardial perfusion with MRI using a modified dual bolus method.
AB  - Quantification of regional myocardial blood flow (rMBF) with first-pass magnetic
      resonance imaging (FP-MRI) requires two contrast agent injections (dual bolus
      technique), inducing error in the determined rMBF if the injections differ. We
      hypothesize that using input and residue curves of the same injection would be
      more reliable. We aim to introduce and evaluate a novel method to correct the
      high concentration arterial input function (AIF) for determination of rMBF.
      Sixteen patients with non-Hodgkin's lymphoma were examined before and after
      chemotherapy. The input function was solved by correcting initial high
      concentration AIF using the ratio of low and high contrast AIF areas, normalized
      by corresponding heart rates (modified dual bolus method). For comparison, the
      scaled low contrast AIF was used as an input function (dual bolus method).
      Unidirectional transfer coefficient K(trans) was calculated using both methods.
      K(trans)-values determined with the dual bolus (0.81 +/- 0.32 ml g(-1) min(-1))
      and modified dual bolus (0.77 +/- 0.42 ml g(-1) min(-1)) methods were in
      agreement (p = 0.21). Mean K(trans)-values increased from 0.76 +/- 0.43 to 0.89
      +/- 0.55 ml g(-1) min(-1) after chemotherapy (p = 0.17). The modified dual bolus
      technique agrees with the dual bolus technique (R2 = 0.899) when the low and high
      contrast injections are similar. However, when this is not the case, the modified
      dual bolus technique may be more reliable.

PMID- 24577345
TI  - Additive effect of combined application of magnesium and MK-801 on analgesic
      action of morphine.
AB  - As previously reported, magnesium ions (Mg(2+)) administered in relatively low
      doses markedly potentiated opioid analgesia in neuropathic pain, in which the
      effectiveness of opioids is limited. Considering that Mg(2+) behaves like an N
      methyl-D-aspartate receptor antagonist, the effect of this ion on the analgesic
      action of morphine was compared with that of MK-801. Acute pain was evoked by
      mechanical or thermal stimuli, whereas neuropathic hyperalgesia was induced by
      streptozotocin (STZ) administration. Magnesium sulphate (40 mg/kg i.p.) or MK-801
      (0.05 mg/kg s.c.) administered alone did not modify the nociceptive threshold to
      acute stimuli or the streptozotocin hyperalgesia but significantly augmented the
      analgesic action of morphine (5 mg/kg i.p.). Furthermore, if these drugs (i.e.
      magnesium sulphate and MK-801) were applied concomitantly, a clear additive
      effect on the analgesic action of morphine occurred in both models of pain.
      Possible explanations of these observations are discussed.

PMID- 24577346
TI  - The relationship between pulmonary function and bone mineral density in healthy
      nonsmoking women: the Korean National Health and Nutrition Examination Survey
      (KNHANES) 2010.
AB  - The aim of this study was to examine the association between pulmonary function
      and bone mineral density (BMD) in subjects who had never smoked. Pulmonary
      function was associated with BMD in premenopausal, but not postmenopausal, women.
      INTRODUCTION: It has been reported that low bone mass is common in patients with
      pulmonary disorders such as chronic obstructive pulmonary disease. However, in
      healthy nonsmoking women, the relationship between bone mass and pulmonary
      function has yet to be clarified. The object of this study was to determine
      whether pulmonary function is related to BMD in healthy nonsmoking women based on
      menopausal status. METHODS: This study was a cross-sectional study based on data
      obtained from the Korean National Health and Nutrition Examination Survey
      (KNHANES), a nationwide representative survey conducted by the Korean Ministry of
      Health and Welfare in 2010. This study included 456 subjects who had never smoked
      and analyzed data concerning pulmonary function and BMD. RESULTS: Functional
      vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) were correlated
      with BMD at lumbar spine, femur neck (FN), and total hip in premenopausal women
      (p = 0.030, p = 0.003, p = 0.019, respectively, for FVC; p = 0.015, p = 0.006, p
      = 0.059, respectively, for FEV1). However, FVC and FEV1 were only correlated with
      BMD at FN in postmenopausal women (p = 0.003 for FVC; p = 0.006 for FEV1). Body
      mass index (BMI), FVC, and FEV1 were significantly related with BMD at FN, even
      after adjusting for age and other confounding factors (beta = 0.334, p < 0.001;
      beta = 0.145, p = 0.017; and beta = 0.129, p = 0.037, respectively) in
      premenopausal women. However, only age and BMI were correlated with BMD at FN
      (beta = -0.268, p = 0.001 and beta = 0.384, p > 0.001) in postmenopausal women
      after adjusting for confounding factors. CONCLUSIONS: Pulmonary function,
      including FVC and FEV1 are associated with BMD at FN in healthy nonsmoking
      premenopausal women but not in postmenopausal women.

PMID- 24577347
TI  - Prevalence of renal impairment among osteoporotic women in the USA, NHANES 2005
      2008: is treatment with bisphosphonates an option?
AB  - Bisphosphonates are the first-line treatment for osteoporotic (OP) women;
      however, therapy is not recommended in severe renal impairment (RI). This study
      examined RI prevalence among OP women. Nearly a quarter of women had moderate RI,
      and 3.59% would not be recommended for bisphosphonates, demonstrating a need for
      better therapeutic alternatives. INTRODUCTION: Bisphosphonates are the
      recommended first-line treatment for postmenopausal women with OP. However,
      bisphosphonates are cleared through the kidney, and therapy is not recommended in
      severe RI due to adverse treatment effects observed with intravenous
      formulations. The objective of this study was to examine the prevalence of RI
      among women with OP aged >=50 years in the USA. METHODS: Women with OP aged >=50
      years were identified using the 2005-2008 National Health and Nutrition
      Examination Survey (NHANES) data. OP was defined as prior OP diagnosis, previous
      hip or spine fracture, or measured lumbar spine/femoral neck bone mineral density
      (BMD) T-score <-2.5. The 2005 Modification of Diet in Renal Disease (MDRD)
      formula was used to calculate the glomerular filtration rate (GFR). Moderate and
      severe RI was defined as GFR 30-59 and 15-29 mL/min, respectively. Bisphosphonate
      therapy was considered not recommended among women with OP if GFR was <35 mL/min.
      RESULTS: The prevalence of OP among women in USA aged >=50 years was 27% (12.7
      million). Nearly a quarter of women with OP (23.54 +/- 2.02%; 2.9 million) had
      moderate RI and 1.88 +/- 0.28% (230,000) had severe RI. Correspondingly,
      bisphosphonate therapy would not be recommended for an estimated 439,000 women
      with OP (3.59 +/- 0.73%). CONCLUSIONS: Nearly a quarter of postmenopausal women
      with OP have moderate RI, and over 3% would not be recommended for bisphosphonate
      treatment. These data reveal a need for better therapeutic alternatives that can
      be used in this patient population.

PMID- 24577350
TI  - Developing Demonstration Test Catchments as a platform for transdisciplinary land
      management research in England and Wales.
AB  - Whilst a large body of plot and field-scale research exists on the sources,
      behaviour and mitigation of diffuse water pollution from agriculture, putting
      this evidence into a practical, context at large spatial scales to inform policy
      remains challenging. Understanding the behaviour of pollutants (nutrients,
      sediment, microbes and pesticides) and the effectiveness of mitigation strategies
      over whole catchments and long timeframes requires new, interdisciplinary
      approaches to organise and undertake research. This paper provides an
      introduction to the demonstration test catchments (DTC) programme, which was
      established in 2009 to gather empirical evidence on the cost-effectiveness of
      combinations of diffuse pollution mitigation measures at catchment scales. DTC
      firstly provides a physical platform of instrumented study catchments in which
      approaches for the mitigation of diffuse agricultural water pollution can be
      experimentally tested and iteratively improved. Secondly, it has established
      national and local knowledge exchange networks between researchers and
      stakeholders through which research has been co-designed. These have provided a
      vehicle to disseminate emerging findings to inform policy and land management
      practice. The role of DTC is that of an outdoor laboratory to develop knowledge
      and approaches that can be applied in less well studied locations. The research
      platform approach developed through DTC has brought together disparate research
      groups from different disciplines and institutions through nationally coordinated
      activities. It offers a model that can be adopted to organise research on other
      complex, interdisciplinary problems to inform policy and operational decision
      making. 

PMID- 24577348
TI  - The clinical diagnosis of osteoporosis: a position statement from the National
      Bone Health Alliance Working Group.
AB  - Osteoporosis causes an elevated fracture risk. We propose the continued use of T
      scores as one means for diagnosis but recommend that, alternatively, hip
      fracture; osteopenia-associated vertebral, proximal humerus, pelvis, or some
      wrist fractures; or FRAX scores with >=3% (hip) or 20% (major) 10-year fracture
      risk also confer an osteoporosis diagnosis. INTRODUCTION: Osteoporosis is a
      common disorder of reduced bone strength that predisposes to an increased risk
      for fractures in older individuals. In the USA, the standard criterion for the
      diagnosis of osteoporosis in postmenopausal women and older men is a T-score of 
      <= -2.5 at the lumbar spine, femur neck, or total hip by bone mineral density
      testing. METHODS: Under the direction of the National Bone Health Alliance, 17
      clinicians and clinical scientists were appointed to a working group charged to
      determine the appropriate expansion of the criteria by which osteoporosis can be
      diagnosed. RESULTS: The group recommends that postmenopausal women and men aged
      50 years should be diagnosed with osteoporosis if they have a demonstrable
      elevated risk for future fractures. This includes having a T-score of less than
      or equal to -2.5 at the spine or hip as one method for diagnosis but also permits
      a diagnosis for individuals in this population who have experienced a hip
      fracture with or without bone mineral density (BMD) testing and for those who
      have osteopenia by BMD who sustain a vertebral, proximal humeral, pelvic, or, in
      some cases, distal forearm fracture. Finally, the term osteoporosis should be
      used to diagnose individuals with an elevated fracture risk based on the World
      Health Organization Fracture Risk Algorithm, FRAX. CONCLUSIONS: As new ICD-10
      codes become available, it is our hope that this new understanding of what
      osteoporosis represents will allow for an appropriate diagnosis when older
      individuals are recognized as being at an elevated risk for fracture.

PMID- 24577351
TI  - Electric coupling between distant nitrate reduction and sulfide oxidation in
      marine sediment.
AB  - Filamentous bacteria of the Desulfobulbaceae family can conduct electrons over
      centimeter-long distances thereby coupling oxygen reduction at the surface of
      marine sediment to sulfide oxidation in deeper anoxic layers. The ability of
      these cable bacteria to use alternative electron acceptors is currently unknown.
      Here we show that these organisms can use also nitrate or nitrite as an electron
      acceptor thereby coupling the reduction of nitrate to distant oxidation of
      sulfide. Sulfidic marine sediment was incubated with overlying nitrate-amended
      anoxic seawater. Within 2 months, electric coupling of spatially segregated
      nitrate reduction and sulfide oxidation was evident from: (1) the formation of a
      4-6-mm-deep zone separating sulfide oxidation from the associated nitrate
      reduction, and (2) the presence of pH signatures consistent with proton
      consumption by cathodic nitrate reduction, and proton production by anodic
      sulfide oxidation. Filamentous Desulfobulbaceae with the longitudinal structures
      characteristic of cable bacteria were detected in anoxic, nitrate-amended
      incubations but not in anoxic, nitrate-free controls. Nitrate reduction by cable
      bacteria using long-distance electron transport to get privileged access to
      distant electron donors is a hitherto unknown mechanism in nitrogen and sulfur
      transformations, and the quantitative importance for elements cycling remains to
      be addressed. 

PMID- 24577352
TI  - The effect of ecological and temporal factors on the composition of Bartonella
      infection in rodents and their fleas.
AB  - The composition of Bartonella infection was explored in wild Gerbillus andersoni
      rodents and their Synosternus cleopatrae fleas. Rodent blood samples and fleas
      were collected in two periods (two different seasons; 4 months apart) from
      juveniles and adult hosts, and their bartonellae lineages were identified by a
      454-pyrosequencing analysis targeting a specific Bartonella citrate synthase gene
      (gltA) fragment. The rate of Bartonella spp. co-infection was estimated and the
      assemblage and distribution of bartonellae lineages across the samples with
      respect to ecological and phylogenetic distance similarities were analyzed.
      Moreover, environmental factors that could explain potential differences between
      samples were investigated. Out of the 91 bartonellae-positive samples, 89% were
      found to be co-infected with more than two phylogenetically distant Bartonella
      genotypes and additional closely related (but distinguishable) variants. These
      bartonellae lineages were distributed in a non-random manner, and a negative
      interaction between lineages was discovered. Interestingly, the overall
      composition of those infections greatly varied among samples. This variability
      was partially explained by factors, such as type of sample (blood versus fleas),
      flea sex and period of collection. This investigation sheds light on the patterns
      of Bartonella infection and the organization of Bartonella lineages in fleas and
      rodents in nature. 

PMID- 24577353
TI  - Reset of a critically disturbed microbial ecosystem: faecal transplant in
      recurrent Clostridium difficile infection.
AB  - Recurrent Clostridium difficile infection (CDI) can be effectively treated by
      infusion of a healthy donor faeces suspension. However, it is unclear what
      factors determine treatment efficacy. By using a phylogenetic microarray
      platform, we assessed composition, diversity and dynamics of faecal microbiota
      before, after and during follow-up of the transplantation from a healthy donor to
      different patients, to elucidate the mechanism of action of faecal infusion.
      Global composition and network analysis of the microbiota was performed in faecal
      samples from nine patients with recurrent CDI. Analyses were performed before and
      after duodenal donor faeces infusion, and during a follow-up of 10 weeks. The
      microbiota data were compared with that of the healthy donors. All patients
      successfully recovered. Their intestinal microbiota changed from a low-diversity
      diseased state, dominated by Proteobacteria and Bacilli, to a more diverse
      ecosystem resembling that of healthy donors, dominated by Bacteroidetes and
      Clostridium groups, including butyrate-producing bacteria. We identified specific
      multi-species networks and signature microbial groups that were either depleted
      or restored as a result of the treatment. The changes persisted over time.
      Comprehensive and deep analyses of the microbiota of patients before and after
      treatment exposed a therapeutic reset from a diseased state towards a healthy
      profile. The identification of microbial groups that constitute a niche for C.
      difficile overgrowth, as well as those driving the reinstallation of a healthy
      intestinal microbiota, could contribute to the development of biomarkers
      predicting recurrence and treatment outcome, identifying an optimal microbiota
      composition that could lead to targeted treatment strategies. 

PMID- 24577354
TI  - Fine-scale spatial patterns in bacterial community composition and function
      within freshwater ponds.
AB  - The extent to which non-host-associated bacterial communities exhibit small-scale
      biogeographic patterns in their distribution remains unclear. Our investigation
      of biogeography in bacterial community composition and function compared samples
      collected across a smaller spatial scale than most previous studies conducted in
      freshwater. Using a grid-based sampling design, we abstracted 100+ samples
      located between 3.5 and 60 m apart within each of three alpine ponds. For every
      sample, variability in bacterial community composition was monitored using a DNA
      fingerprinting methodology (automated ribosomal intergenic spacer analysis)
      whereas differences in bacterial community function (that is, carbon substrate
      utilisation patterns) were recorded from Biolog Ecoplates. The exact spatial
      position and dominant physicochemical conditions (for example, pH and
      temperature) were simultaneously recorded for each sample location. We assessed
      spatial differences in bacterial community composition and function within each
      pond and found that, on average, community composition or function differed
      significantly when comparing samples located >20 m apart within any pond.
      Variance partitioning revealed that purely spatial variation accounted for more
      of the observed variability in both bacterial community composition and function
      (range: 24-38% and 17-39%) than the combination of purely environmental variation
      and spatially structured environmental variation (range: 17-32% and 15-20%).
      Clear spatial patterns in bacterial community composition, but not function were
      observed within ponds. We therefore suggest that some of the observed variation
      in bacterial community composition is functionally 'redundant'. We confirm that
      distinct bacterial communities are present across unexpectedly small spatial
      scales suggesting that populations separated by distances of >20 m may be
      dispersal limited, even within the highly continuous environment of lentic water.

PMID- 24577356
TI  - Right ventricular diastolic performance in children with pulmonary arterial
      hypertension associated with congenital heart disease: correlation of
      echocardiographic parameters with invasive reference standards by high-fidelity
      micromanometer catheter.
AB  - BACKGROUND: Right ventricular diastolic dysfunction influences outcomes in
      pulmonary arterial hypertension (PAH), but echocardiographic parameters have not
      been investigated in relation to invasive reference standards in pediatric PAH.
      We investigated echocardiographic parameters of right ventricular diastolic
      function in children with PAH in relation to simultaneously measured invasive
      reference measures. METHODS AND RESULTS: We prospectively recruited children
      undergoing a clinically indicated cardiac catheterization for evaluation of PAH
      and pulmonary vasoreactivity testing. Echocardiography was performed
      simultaneously with invasive reference measurements by high-fidelity
      micromanometer catheter. For analysis, patients were divided into shunt and
      nonshunt groups. Sixteen children were studied. In the group as a whole,
      significant correlations were found among tau and tricuspid deceleration time,
      E', E/E', TimeE-E', A wave velocity, and global early and late diastolic strain
      rate. dp/dt minimum correlated significantly with late diastolic tricuspid
      annular velocity (A'), tissue Doppler imaging-derived systolic:diastolic duration
      ratio, and global late diastolic strain rate. End-diastolic pressure correlated
      significantly with tissue Doppler imaging-derived systolic:diastolic duration
      ratio. On multivariate analysis, tricuspid deceleration time, TimeE-E', and
      global early diastolic strain rate were independent predictors of tau, whereas
      tissue Doppler imaging-derived systolic:diastolic duration ratio was an
      independent predictor of dp/dt minimum. In general, correlations between
      echocardiographic and invasive parameters were better in the shunt group than in
      the nonshunt group. CONCLUSIONS: Echocardiography correlates with invasive
      reference measures of right ventricular diastolic function in children with PAH,
      although it does not differentiate between early versus late diastolic
      abnormalities. Newer echocardiographic techniques may have added value to assess
      right ventricular diastolic dysfunction in this population.

PMID- 24577357
TI  - Polypeptide films via N-carboxyanhydride ring-opening polymerization (NCA-ROP):
      past, present and future.
AB  - The formation of surface-grafted polypeptide films and interfaces via N
      carboxyanhydride ring-opening polymerization (NCA-ROP) holds great potential for
      the facile preparation of next-generation multifunctional and responsive
      materials with excellent biocompatibility, biodegradability, tunable
      conformations and chemical functionalities. Therefore, the aim of this feature
      article is to provide a topical review of developments in the area of polypeptide
      films derived through NCA-ROP. It is evident that studies reported thus far have
      only started to unveil the full potential of peptide-based interfaces and
      materials, and with continued advancements it is anticipated that the strategic
      combination of NCA-ROP with modern synthetic chemistries will continue to yield
      versatile platforms for broader applications in the fields of polymer
      therapeutics, tissue engineering, (bio)nanocoatings, (bio)chemosensors, catalysis
      and separation technologies. 

PMID- 24577355
TI  - Noncalcified coronary plaque volumes in healthy people with a family history of
      early onset coronary artery disease.
AB  - BACKGROUND: Although age and sex distributions of calcified coronary plaque have
      been well described in the general population, noncalcified plaque (NCP)
      distributions remain unknown. This is important because NCP is a putative
      precursor for clinical coronary artery disease and could serve as a sentinel for
      aggressive primary prevention, especially in high-risk populations. We examined
      the distributions of NCP and calcified coronary plaque in healthy 30- to 74-year
      old individuals from families with early onset coronary artery disease. METHODS
      AND RESULTS: Participants in the GeneSTAR family study (N=805), mean age 51.1+/
      10.8 years, 56% women, were screened for coronary artery disease risk factors and
      coronary plaque using dual-source computed tomographic angiography. Plaque
      volumes (mm(3)) were quantified using a validated automated method. The
      prevalence of coronary plaque was 57.8% in men and 35.8% in women (P<0.0001). NCP
      volume increased with age (P<0.001) and was higher in men than women (P<0.001).
      Although NCP, as a percentage of total plaque, was inversely related to age
      (P<0.01), NCP accounted for most of the total plaque volume at all ages,
      especially in men and women <55 years (>70% and >80%, respectively). Higher
      Framingham risk was associated with the number of affected vessels (P<0.01), but
      44% of men and 20.8% of women considered intermediate risk had left main and 3
      vessel disease involvement. CONCLUSIONS: The majority of coronary plaque was
      noncalcified, particularly in younger individuals. These findings support the
      importance of assessing family history and suggest that early primary prevention
      interventions may be warranted at younger ages in families with early onset
      coronary artery disease.

PMID- 24577358
TI  - A modified fall risk assessment tool that is specific to physical function
      predicts falls in community-dwelling elderly people.
AB  - BACKGROUND AND PURPOSE: Developing a practical fall risk assessment tool to
      predict the occurrence of falls in the primary care setting is important because
      investigators have reported deterioration of physical function associated with
      falls. Researchers have used many performance tests to predict the occurrence of
      falls. These performance tests predict falls and also assess physical function
      and determine exercise interventions. However, the need for such specialists as
      physical therapists to accurately conduct these tests limits their use in the
      primary care setting. Questionnaires for fall prediction offer an easy way to
      identify high-risk fallers without requiring specialists. Using an existing fall
      assessment questionnaire, this study aimed to identify items specific to physical
      function and determine whether those items were able to predict falls and
      estimate physical function of high-risk fallers. METHODS: The analysis consisted
      of both retrospective and prospective studies and used 2 different samples
      (retrospective, n = 1871; prospective, n = 292). The retrospective study and 3
      month prospective study comprised community-dwelling individuals aged 65 years or
      older and older adults using community day centers. The number of falls, risk
      factors for falls (15 risk factors on the questionnaire), and physical function
      determined by chair standing test (CST) and Timed Up and Go Test (TUGT) were
      assessed. The retrospective study selected fall risk factors related to physical
      function. The prospective study investigated whether the number of selected risk
      factors could predict falls. The predictive power was determined using the area
      under the receiver operating characteristic curve. RESULTS: Seven of the 15 risk
      factors were related to physical function. The area under the receiver operating
      characteristic curve for the sum of the selected risk factors of previous falls
      plus the other risk factors was 0.82 (P = .00). The best cutoff point was 4 risk
      factors, with sensitivity and specificity of 84% and 68%, respectively. The mean
      values for the CST and TUGT at the best cutoff point were 12.9 and 12.5 seconds,
      respectively. In the retrospective study, the values for the CST and TUGT
      corresponding to the best cutoff point from the prospective study were 13.2 and
      11.4 seconds, respectively. DISCUSSION: This study confirms that a screening tool
      comprising 7 fall risk factors can be used to predict falls. The values for the
      CST and TUGT corresponding to the best cutoff point for the selected 7 risk
      factors determined in our prospective study were similar to the cutoff points for
      the CST and TUGT in previous studies for fall prediction. We propose that the sum
      of the selected risk factors of previous falls plus the other risk factors may be
      identified as the estimated value for physical function. CONCLUSIONS: These
      findings may contribute to earlier identification of high-risk fallers and
      intervention for fall prevention.

PMID- 24577361
TI  - Mapping the miRNA interactome by cross-linking ligation and sequencing of hybrids
      (CLASH).
AB  - RNA-RNA interactions have critical roles in many cellular processes, but studying
      them is difficult and laborious. Here we describe an experimental procedure,
      termed cross-linking ligation and sequencing of hybrids (CLASH), which allows
      high-throughput identification of sites of RNA-RNA interaction. During CLASH, a
      tagged bait protein is UV-cross-linked in cell cultures to stabilize RNA
      interactions, and it is purified under denaturing conditions. RNAs associated
      with the bait protein are partially truncated, and the ends of RNA duplexes are
      ligated together. After linker addition, cDNA library preparation and high
      throughput sequencing, the ligated duplexes give rise to chimeric cDNAs, which
      unambiguously identify RNA-RNA interaction sites independent of bioinformatic
      predictions. This protocol is optimized for studying miRNA targets bound by
      Argonaute (AGO) proteins, but it should be easily adapted for other RNA-binding
      proteins and classes of RNA. The protocol requires ~5 d to complete, excluding
      the time required for high-throughput sequencing and bioinformatic analyses. 

PMID- 24577359
TI  - A general protocol for the generation of Nanobodies for structural biology.
AB  - There is growing interest in using antibodies as auxiliary tools to crystallize
      proteins. Here we describe a general protocol for the generation of Nanobodies to
      be used as crystallization chaperones for the structural investigation of diverse
      conformational states of flexible (membrane) proteins and complexes thereof. Our
      technology has a competitive advantage over other recombinant crystallization
      chaperones in that we fully exploit the natural humoral response against native
      antigens. Accordingly, we provide detailed protocols for the immunization with
      native proteins and for the selection by phage display of in vivo-matured
      Nanobodies that bind conformational epitopes of functional proteins. Three
      representative examples illustrate that the outlined procedures are robust,
      making it possible to solve by Nanobody-assisted X-ray crystallography in a time
      span of 6-12 months. 

PMID- 24577363
TI  - Improving care of children with endocrine diseases.

PMID- 24577360
TI  - Microfluidic, marker-free isolation of circulating tumor cells from blood
      samples.
AB  - The ability to isolate and analyze rare circulating tumor cells (CTCs) has the
      potential to further our understanding of cancer metastasis and enhance the care
      of cancer patients. In this protocol, we describe the procedure for isolating
      rare CTCs from blood samples by using tumor antigen-independent microfluidic CTC
      iChip technology. The CTC-iChip uses deterministic lateral displacement, inertial
      focusing and magnetophoresis to sort up to 107 cells/s. By using two-stage
      magnetophoresis and depletion antibodies against leukocytes, we achieve 3.8-log
      depletion of white blood cells and a 97% yield of rare cells with a sample
      processing rate of 8 ml of whole blood/h. The CTC-iChip is compatible with
      standard cytopathological and RNA-based characterization methods. This protocol
      describes device production, assembly, blood sample preparation, system setup and
      the CTC isolation process. Sorting 8 ml of blood sample requires 2 h including
      setup time, and chip production requires 2-5 d.

PMID- 24577362
TI  - Chemical ablation of tumor-initiating human pluripotent stem cells.
AB  - The tumorigenicity of human pluripotent stem cells (hPSCs) is widely acknowledged
      as a major obstacle that withholds their application in regenerative medicine.
      This protocol describes two efficient and robust ways to chemically eliminate the
      tumor-initiating hPSCs from monolayer culture. The protocol details how to
      maintain and differentiate hPSCs, how to apply chemical inhibitors to cultures of
      hPSCs and their differentiated progeny, and how to assess the purity of the
      resultant cell cultures using in vitro and in vivo assays. It also describes how
      to rescue the cytotoxic effect. The elimination and the rescue assay can be
      completed within 3-5 d, the in vitro assessment requires another day, and the in
      vivo assessment requires up to 12 additional weeks. 

PMID- 24577364
TI  - Association of low serum complement C3 with reduced patient and renal survival in
      antimyeloperoxidase-associated small-vessel vasculitis.
AB  - OBJECTIVE: This study aimed to determine the value of hypocomplementemia in
      predicting the renal and patient survival of patients with antineutrophil
      cytoplasmatic antibody-associated vasculitis (AAV). METHODS: A retrospective
      analysis of 30 consecutive patients who were diagnosed with AAV and followed at
      our hospital from 1996 to 2011 was performed. Renal outcome was determined by the
      Modification of Diet in Renal Disease equation. Disease outcome measures included
      patient survival and accrual of chronic kidney disease (CKD) defined as an
      estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m(2) from the date of
      diagnosis. Logistic regression analysis was used to identify predictors of
      survival. RESULTS: At presentation, 6 (20%) patients had a low C3 level, which
      was significantly associated with older age (p = 0.009), higher C-reactive
      protein (p = 0.02), a lower eGFR (p = 0.03), and anti-MPO antibody positivity (p
      = 0.03). A low C3 level at presentation was significantly associated with a
      reduced eGFR at the last study visit (p = 0.015, OR = 11; 95% CI 1.27-95.15).
      During a mean follow-up of 9.0 +/- 6.2 years, 8 (26.6%) patients had accrued CKD
      that was significantly associated with low C3 levels at presentation (p = 0.002,
      OR = 22; 95% CI 2.36-204.7). Mortality was significantly associated with low
      serum C3 levels at presentation (p = 0.02). CONCLUSION: We found that a low serum
      C3 level at the time of diagnosis was significantly associated with reduced renal
      and patient survival in patients with anti-MPO AAV. Our results suggest a role
      for complement activation in the pathogenesis of AAV.

PMID- 24577365
TI  - Structural brain development and depression onset during adolescence: a
      prospective longitudinal study.
AB  - OBJECTIVE: The authors sought to investigate whether the structural development
      of limbic, striatal, and prefrontal regions that are critically implicated in the
      pathophysiology of depression is associated with adolescent-onset depression.
      METHOD: In a longitudinal design, a risk enriched community sample of 86
      adolescents (41 of them female) who had no history of depressive disorders
      participated in neuroimaging assessments conducted during early (age 12) and
      midadolescence (age 16). Onset of depressive disorders was assessed for the
      period spanning early to late adolescence (ages 12 to 18). Thirty participants
      experienced a first episode of a depressive disorder during the follow-up period.
      The authors assessed whether onset of depressive disorder was associated with
      structural change in limbic, striatal, and prefrontal cortical regions from early
      to mid-adolescence. RESULTS: Volumetric change in the hippocampus, amygdala, and
      putamen from early to mid-adolescence was associated with the onset of depression
      during adolescence. Attenuated growth of the hippocampus and attenuated reduction
      in putamen volume over time were associated with the onset of depression. Sex
      moderated the association between amygdala growth and depression such that
      exaggerated growth and attenuated growth of the amygdala were associated with
      depression in females and males, respectively. Across time, smaller nucleus
      accumbens volume was associated with depression in females only. CONCLUSIONS:
      These findings suggest that alterations in the developmental trajectories of
      limbic and striatal regions during adolescence may represent a neurobiological
      manifestation of a risk factor for the development of depression during this
      critical period and thus may provide clues as to etiological mechanisms of this
      disorder.

PMID- 24577366
TI  - Retinoblastoma incidence patterns in the US Surveillance, Epidemiology, and End
      Results program.
AB  - IMPORTANCE Several studies have found no temporal or demographic differences in
      the incidence of retinoblastoma except for age at diagnosis, whereas other
      studies have reported variations in incidence by sex and race/ethnicity.
      OBJECTIVE To examine updated US retinoblastoma incidence patterns by sex, age at
      diagnosis, laterality, race/ethnicity, and year of diagnosis. DESIGN, SETTING,
      AND PARTICIPANTS The Surveillance, Epidemiology, and End Results (SEER) databases
      were examined for retinoblastoma incidence patterns by demographic and tumor
      characteristics. We studied 721 children in SEER 18 registries, 659 in SEER 13
      registries, and 675 in SEER 9 registries. MAIN OUTCOMES AND MEASURES Incidence
      rates, incidence rate ratios (IRRs), and annual percent changes in rates. RESULTS
      During 2000-2009 in SEER 18, there was a significant excess of total
      retinoblastoma among boys compared with girls (IRR, 1.18; 95% CI, 1.02 to 1.36),
      in contrast to earlier reports of a female predominance. Bilateral retinoblastoma
      among white Hispanic boys was significantly elevated relative to white non
      Hispanic boys (IRR, 1.81; 95% CI, 1.22 to 2.79) and white Hispanic girls (IRR,
      1.75; 95% CI, 1.11 to 2.91) because of less rapid decreases in bilateral rates
      since the 1990s among white Hispanic boys than among the other groups.
      Retinoblastoma rates among white non-Hispanics decreased significantly since 1992
      among those younger than 1 year and since 1998 among those with bilateral
      disease. CONCLUSIONS AND RELEVANCE Although changes in the availability of
      prenatal screening practices for retinoblastoma may have contributed to these
      incidence patterns, further research is necessary to determine their actual
      effect on the changing incidence of retinoblastoma in the US population. In
      addition, consistent with other cancers, an excess of retinoblastoma diagnosed in
      boys suggests a potential effect of sex on cancer origin. 

PMID- 24577367
TI  - Do axial-flow LVADs unload better than centrifugal-flow LVADs?

PMID- 24577368
TI  - A mock circulatory system to assess the performance of continuous-flow left
      ventricular assist devices (LVADs): does axial flow unload better than
      centrifugal LVAD?
AB  - Hemodynamic performances comparisons between different types of left ventricular
      assist devices (LVADs) remain difficult in a clinical context. The aim of this
      study was to create an experimental model to assess and compare two types of LVAD
      under hemodynamic conditions that simulated physical effort and pulmonary
      hypertension. An experimental mock circulatory system was created to simulate the
      systemic and pulmonary circulations and consisted of pulsatile left and right
      cardiac simulators (cardiowest pump), air/water tanks to model compliances, and
      tubes to model the venous and arterial resistances. Two types of continuous-flow
      ventricular assist devices were connected to this pulsated model: an axial flow
      pump, Heartmate II (HTM II), and a centrifugal pump, VentrAssist (VTA). The
      hemodynamic conditions at rest and during exercise were replicated. Mean aortic
      pressures were not significantly different at rest and during effort but mean
      flow under maximum pump speed was higher with HTM II (13 L vs. 10 L, p = 0.02).
      Left atrial pressure was lower at rest and during effort for the HTM II (11 mm Hg
      vs. 3 mm Hg, p = 0.02 and 9 mm Hg vs. 2 mm Hg, p = 0.008) than with the VTA, but
      with greater risk of left-ventricle suck-down for the axial flow. Power
      consumption for a similar flow was lower with the VTA during rest (4.7 W vs. 6.9
      W, p = 0.002) and during effort (4.3 W vs. 6.6 W, p = 0.008). In case of high
      pulmonary vascular resistance with preserved right ventricular function, lower
      right ventricular pressure was obtained with HTM II (21 mm Hg vs. 28 mm Hg, p =
      0.03). Observed results are in favor of a better discharge of the left and right
      cavities with the HTM II compared to the VTA yet with a higher risk of left
      cavity collapse occurrence. 

PMID- 24577370
TI  - Pharmacist-managed international normalized ratio patient self-testing is
      associated with increased time in therapeutic range in patients with left
      ventricular assist devices at an academic medical center.
AB  - Patients with left ventricular assist devices (LVADs) are at increased risk of
      bleeding and thrombotic complications making warfarin therapy particularly
      challenging. Patient self-testing (PST) using point-of-care international
      normalized ratio (INR) devices has shown favorable outcomes in other populations,
      but the use of PST in LVAD patients has not been well described. The purpose of
      this study was to evaluate the effectiveness of pharmacist-managed INR PST versus
      usual care (UC) in patients with LVADs at a single center. We performed a
      retrospective cohort study of adult patients (in a 1:4 ratio PST versus UC)
      implanted with an LVAD (HeartMate II or HVAD) treated with warfarin from January
      1, 2007, to January 31, 2013. We reviewed all INRs and bleeding/thrombotic events
      in LVAD patients whose anticoagulation was managed by clinical pharmacists via
      INR PST versus UC and calculated a percent time in therapeutic range (%TTR) by
      Rosendaal method. Fifty-five patients were studied. Demographic data were
      generally similar between the cohorts. Mean %TTR was higher in the PST cohort
      versus UC (44.4% vs. 30.6%, p = 0.026). There was no difference in the rate per
      patient-year of bleeding (0.23 vs. 0.33, p = 0.55) or thrombotic events (0.12 vs.
      0.13, p = 0.88). Pharmacist-managed INR PST is associated with an increased %TTR
      in patients with LVADs. 

PMID- 24577369
TI  - Home discharge and out-of-hospital follow-up of total artificial heart patients
      supported by a portable driver system.
AB  - To enhance ambulation and facilitate hospital discharge of total artificial heart
      (TAH)-supported patients, we adapted a mobile ventricular assistance device (VAD)
      driver (Excor) for TAH use and report on the performance of Excor-driven TAH
      patients discharged home. Ten patients stabilized on a TAH, driven by the CSS
      ("Circulatory Support System"), were progressively switched over to the Excor in
      hospital over 14 days as a pilot, with daily hemodynamics and laboratory
      parameters measured. Twenty-two stable TAH patients were subsequently placed on
      the Excor, trained, and discharged home. Clinical and hemodynamic parameters were
      followed. All pilot study patients were clinically stable on the Excor, with no
      decrease in TAH output noted (6.3 + 0.3 L/min [day 1] vs. 5.8 + 0.2 L/min [day
      14], p = 0.174), with a trend suggesting improvement of both hepatic and renal
      function. Twenty-two TAH patients were subsequently successfully discharged home
      on the portable driver and were supported out of hospital for up to 598 days
      (range, 2-598; mean = 179 +/- 140 days), remaining ambulatory, New York Heart
      Association (NYHA) class I or II, and free of readmission for 88.5% of the time
      of support. TAH patients may be effectively and safely supported by a mobile
      drive system. As such, the utility of the TAH may be extended to support patients
      beyond the hospital, at home, with overall ambulatory freedom. 

PMID- 24577372
TI  - Acquired von Willebrand disease during CentriMag support is associated with high
      prevalence of bleeding during support and after transition to heart replacement
      therapy.
AB  - The Levitronix CentriMag is a magnetically levitated centrifugal-flow pump that
      can be implanted rapidly in the operating room for both right and left
      ventricular support. Recently, continuous-flow pumps have been associated with
      excessive bleeding, which can be at least partially explained by acquired von
      Willebrand disease (vWD). We investigated whether acquired vWD occurs during
      CentriMag support and determined the frequency of bleeding complications during
      device support as well as after transition to long-term support. We found that
      acquired vWD is common early post CentriMag implantation and is associated with
      frequent bleeding events and high requirement of blood products. 

PMID- 24577371
TI  - Sex-specific outcomes in patients receiving continuous-flow left ventricular
      devices as a bridge to transplantation or destination therapy.
AB  - Reports on sex-related outcomes in left ventricular assist device (LVAD) patients
      are conflicting. In addition, females have been underrepresented in most
      multicenter randomized controlled trials for mechanical circulatory support
      (MCS). The objective of our study was to analyze our experience implanting 130
      continuous-flow LVADs and to determine the impact of sex on survival. We
      identified 130 patients who underwent implantation of a continuous-flow LVAD at
      our institution. Patients were stratified into two groups based on sex. Variables
      were compared using two-sided t-tests, chi(2) tests, Cox proportional hazards
      models, and log-rank tests to determine whether there was a difference between
      the two groups and if sex was a significant independent predictor of outcome. Of
      the 130 patients, 35 were females and 95 were males. Female patients had worse
      pre-LVAD cardiac output and cardiac index and were more likely to be on MCS at
      the time of implantation. Male patients had worse renal function. Survival was
      analogous for both cohorts with 30 day, 6 month, 1 year, and 2 year survivals of
      97%, 90.8%, 90.8%, and 84.3%, respectively, for female patients versus 94.7%,
      87.9%, 78.4%, and 72.8%, respectively, for male patients. The incidence of other
      LVAD-related complications was also similar in both groups. Gender did not
      predict postoperative mortality on univariate analysis. Contrary to most
      published reports, female and male LVAD patients have similar postoperative and
      midterm survival, length of hospital stay, readmission rates, and postoperative
      complications. It appears that females have gained more benefit from newer
      generation devices compared to males.

PMID- 24577373
TI  - Implantation of the HeartMate II and HeartWare left ventricular assist devices in
      patients with duchenne muscular dystrophy: lessons learned from the first
      applications.
AB  - Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder affecting 1
      in 3,500 males, characterized by progressive skeletal muscle weakness and death
      secondary to cardiac or respiratory failure in the 2nd or 3rd decade. Being a
      progressive disease, patients are rarely candidates for cardiac transplantation
      and death from dilated cardiomyopathy (DCM) is common. Implantation of left
      ventricular assist device (LVAD) offers the potential to alter clinical
      trajectory by alleviating heart failure symptoms. We report implantation of
      HeartMate II device in a 29-year-old male patient and HeartWare device in a 23
      year-old female patient, each with DMD and end-stage DCM. By improving cardiac
      output, we were able to achieve resolution of the symptoms of heart failure and
      improve their quality of life. Preoperative planning and patient selection played
      a significant role in the postoperative course for these patients. These cases
      represent the first use for each device in this patient population and the first
      reported LVAD implantations in patients with DMD in North America. 

PMID- 24577374
TI  - The relative ineffectiveness of criminal network disruption.
AB  - Researchers, policymakers and law enforcement agencies across the globe struggle
      to find effective strategies to control criminal networks. The effectiveness of
      disruption strategies is known to depend on both network topology and network
      resilience. However, as these criminal networks operate in secrecy, data-driven
      knowledge concerning the effectiveness of different criminal network disruption
      strategies is very limited. By combining computational modeling and social
      network analysis with unique criminal network intelligence data from the Dutch
      Police, we discovered, in contrast to common belief, that criminal networks might
      even become 'stronger', after targeted attacks. On the other hand increased
      efficiency within criminal networks decreases its internal security, thus
      offering opportunities for law enforcement agencies to target these networks more
      deliberately. Our results emphasize the importance of criminal network
      interventions at an early stage, before the network gets a chance to (re
      )organize to maximum resilience. In the end disruption strategies force criminal
      networks to become more exposed, which causes successful network disruption to
      become a long-term effort. 

PMID- 24577375
TI  - Straightforward access to 4-membered sulfurated heterocycles: introducing a
      strategy for the single and double functionalization of thietane 1-oxide.
AB  - A strategy for the stereoselective functionalization of thietane 1-oxide has been
      developed. Mono (C2 substituted) and doubly (C2, C4 disubstituted) functionalized
      thietanes have been obtained from the readily available thietane 1-oxide by using
      the corresponding organometallic intermediates that reacted with electrophiles
      leaving intact the 4-membered ring. 

PMID- 24577376
TI  - Chemical composition, biological and cytotoxic activities of plant extracts and
      compounds isolated from Ferula lutea.
AB  - The present work describes the phytochemical study on Ferula lutea flowers. Total
      phenolics and flavonoids of the n-butanol and ethyl acetate extracts were
      quantified (phenolics [40.68-52.29 mg gallic acid equivalent/g of dry weight],
      flavonoids [12.38-14.72 mg quercitin/g dry weight]). Two diastereoisomers were
      isolated and identified using spectroscopic techniques (1D, 2D NMR and GC-MS).
      The extracts and diastereoisomers were tested for antioxidant,
      antiacetylcholinesterase, antimicrobial, antidiabectic, cytotoxic (leukemia cell
      line) activities and allelopathic potentialities. The strongest antioxidant
      activity was obtained for the ethyl acetate extract (IC50 = 12.8 +/- 1.29 ug/mL).
      The two extracts exhibited high antidiabetic activity (54.1 and 52.1% at 40
      ug/mL).

PMID- 24577377
TI  - Nonalcoholic fatty liver disease may cause thrombocytopenia.

PMID- 24577378
TI  - Toxicity of the mycotoxin citrinin and its metabolite dihydrocitrinone and of
      mixtures of citrinin and ochratoxin A in vitro.
AB  - Citrinin (CIT) and ochratoxin A (OTA) are mycotoxins produced by several species
      of the genera Aspergillus, Penicillium and Monascus. Both can be present as
      contaminants in various food commodities and in animal feed. The occurrence and
      toxicity of OTA and human exposure have been intensively studied, but for CIT
      such data are scarce by comparison. Recently, dihydrocitrinone (DH-CIT) was
      detected as main metabolite of CIT in human urine, and co-occurrence of CIT and
      OTA was shown in human blood plasma (Blaszkewicz et al. in Arch Toxicol 87:1087
      1094, 2013). In light of these new findings, we have now investigated the
      toxicity of the metabolite DH-CIT in comparison with CIT and analysed the effects
      of mixtures of CIT and OTA in vitro. The cytotoxic potency of DH-CIT (IC50 of
      320/200 MUM) was distinctly lower compared with CIT (IC50 of 70/62 MUM) after
      treatment of V79 cells for 24 and 48 h. Whereas CIT induced a concentration
      dependent increase in micronucleus frequencies at concentrations >=30 MUM, DH-CIT
      showed no genotoxic effect up to 300 MUM. Thus, conversion of CIT to DH-CIT in
      humans can be regarded as a detoxification step. Mixtures of CIT and OTA exerted
      additive effects in cytotoxicity assays. The effect of CIT and OTA mixtures on
      induction of micronuclei varied dependent on the used concentrations between
      additive for low MUM concentrations and more-than-additive for high MUM
      concentrations. Effects on cell cycle were mostly triggered by OTA when both
      mycotoxins were used in combination. The implications of our and related in vitro
      studies are discussed with respect to in vivo concentrations of CIT and OTA,
      which are found in animals and in humans. 

PMID- 24577379
TI  - Determination of normal beta values via radio frequency echo-tracking technique
      in a healthy Central European population.
AB  - The aim of our article is to report normal values of beta stiffness parameter and
      pulse wave velocity (PWV) determined via radio frequency echo-tracking technique
      first in different age groups of a healthy Central European population in both
      gender. Values of PWV and beta stiffness parameters increase normally during
      aging and in certain vascular diseases including atherosclerosis. Detection of
      significant deviation from the normal values provides opportunity to diagnose the
      early stage atherosclerosis before morphological changes become visible and while
      therapy is more efficient. Atherosclerosis is responsible great percentage of
      morbidity and mortality in western world population therefore the detection of
      these parameters could be important and useful in primary and secondary
      prevention. 

PMID- 24577380
TI  - Evaluation of multimodality imaging using image fusion with ultrasound tissue
      elasticity imaging in an experimental animal model.
AB  - PURPOSE: To evaluate the ultrasound tissue elasticity imaging by comparison to
      multimodality imaging using image fusion with Magnetic Resonance Imaging (MRI)
      and conventional grey scale imaging with additional elasticity-ultrasound in an
      experimental small-animal-squamous-cell carcinoma-model for the assessment of
      tissue morphology. METHOD AND MATERIALS: Human hypopharynx carcinoma cells were
      subcutaneously injected into the left flank of 12 female athymic nude rats. After
      10 days (SD +/- 2) of subcutaneous tumor growth, sonographic grey scale including
      elasticity imaging and MRI measurements were performed using a high-end
      ultrasound system and a 3T MR. For image fusion the contrast-enhanced MRI DICOM
      data set was uploaded in the ultrasonic device which has a magnetic field
      generator, a linear array transducer (6-15 MHz) and a dedicated software package
      (GE Logic E9), that can detect transducers by means of a positioning system.
      Conventional grey scale and elasticity imaging were integrated in the image
      fusion examination. After successful registration and image fusion the registered
      MR-images were simultaneously shown with the respective ultrasound sectional
      plane. Data evaluation was performed using the digitally stored video sequence
      data sets by two experienced radiologist using a modified Tsukuba Elasticity
      score. The colors "red and green" are assigned for an area of soft tissue, "blue"
      indicates hard tissue. RESULTS: In all cases a successful image fusion and plan
      registration with MRI and ultrasound imaging including grey scale and elasticity
      imaging was possible. The mean tumor volume based on caliper measurements in 3
      dimensions was ~323 mm3. 4/12 rats were evaluated with Score I, 5/12 rates were
      evaluated with Score II, 3/12 rates were evaluated with Score III. There was a
      close correlation in the fused MRI with existing small necrosis in the tumor.
      None of the scored II or III lesions was visible by conventional grey scale.
      CONCLUSION: The comparison of ultrasound tissue elasticity imaging enables a
      secure differentiation between different tumor tissue areas in comparison to
      image fusion with MRI in our small study group. Therefore ultrasound tissue
      elasticity imaging might be used for fast detection of tumor response in the
      future whereas conventional grey scale imaging alone could not provide the
      additional information. By using standard, contrast-enhanced MRI images for
      reliable and reproducible slice positioning, the strongly user-dependent
      limitation of ultrasound tissue elasticity imaging may be overcome, especially
      for a comparison between baseline and follow-up measurements.

PMID- 24577381
TI  - The influence of winter swimming on the rheological properties of blood.
AB  - The aim of this study was to analyze the changes in blood rheology resulting from
      regular winter swimming. The study was carried out on 12 male winter swimmers.
      Venous blood for morphological, biochemical and rheological analysis was sampled
      twice from each winter swimmer - at the beginning of the season and after its
      completion. There were no significant changes detected in the median values of
      most blood morphological parameters. The only exception pertained to MCHC which
      was significantly lower after the season. Winter swimming entailed significant
      decrease in median elongation index values at shear stress levels of 0.30 Pa and
      0.58 Pa, and significant increase in median values of this parameter at shear
      stress levels >=1.13 Pa. No significant changes were observed in winter swimmers'
      median values of aggregation indices and plasma viscosity. The median level of
      glucose was lower post winter swimming in comparison to the pre-seasonal values.
      In contrast, one season of winter swimming did not influence swimmers' median
      value of fibrinogen concentration. In summary, this study revealed positive
      effects of winter swimming on the rheological properties of blood, manifested by
      an increase in erythrocyte deformability without accompanying changes in
      erythrocyte aggregation. 

PMID- 24577382
TI  - Evaluation of treatment response after chemoembolisation (TACE) in hepatocellular
      carcinoma using real time image fusion of contrast-enhanced ultrasound (CEUS) and
      computed tomography (CT)--preliminary results.
AB  - OBJECTIVE: To evaluate treatment response of hepatocellular carcinoma (HCC) after
      transarterial chemoembolization (TACE) with a new real-time imaging fusion
      technique of contrast-enhanced ultrasound (CEUS) with multi-slice detection
      computed tomography (CT) in comparison to conventional post-interventional follow
      up. MATERIAL AND METHODS: 40 patients with HCC (26 male, ages 46-81 years) were
      evaluated 24 hours after TACE using CEUS with ultrasound volume navigation and
      image fusion with CT compared to non-enhanced CT and follow-up contrast-enhanced
      CT after 6-8 weeks. Reduction of tumor vascularization to less than 25% was
      regarded as "successful" treatment, whereas reduction to levels >25% was
      considered as "partial" treatment response. Homogenous lipiodol retention was
      regarded as successful treatment in non-enhanced CT. RESULTS: Post-interventional
      image fusion of CEUS with CT was feasible in all 40 patients. In 24 patients
      (24/40), post-interventional image fusion with CEUS revealed residual tumor
      vascularity, that was confirmed by contrast-enhanced CT 6-8 weeks later in 24/24
      patients. In 16 patients (16/40), post-interventional image fusion with CEUS
      demonstrated successful treatment, but follow-up CT detected residual viable
      tumor (6/16). Non-enhanced CT did not identify any case of treatment failure.
      Image fusion with CEUS assessed treatment efficacy with a specificity of 100%,
      sensitivity of 80% and a positive predictive value of 1 (negative predictive
      value 0.63). CONCLUSIONS: Image fusion of CEUS with CT allows a reliable, highly
      specific post-interventional evaluation of embolization response with good
      sensitivity without any further radiation exposure. It can detect residual viable
      tumor at early state, resulting in a close patient monitoring or re-therapy.

PMID- 24577383
TI  - Ambient temperature and severity of intracerebral haemorrhage: the INTERACT1
      study.
AB  - BACKGROUND: Intracerebral haemorrhage (ICH) rates increase in winter months. We
      aimed to determine associations of ambient temperature with clinical severity and
      haematoma size in acute ICH among Chinese participants in the Intensive Blood
      Pressure Reduction in Acute Cerebral Haemorrhage Trial (INTERACT1). METHODS:
      INTERACT1 was a randomised controlled trial of early intensive blood pressure
      lowering in 404 patients with acute ICH. Among 304 (79%) Chinese participants,
      data on ambient temperature (average, minimum, maximum and range) on the day of
      ICH onset obtained from the China Meteorological Data Sharing Service System were
      linked to measures of clinical severity: elevated National Institute of Health
      Stroke Scale score (>10), low Glasgow Coma Scale score (<14), and haematoma
      parameters at the time of presentation. Clinical outcomes were evaluated in
      logistic regression models, and haematoma volume (log transformed, with and
      without intraventricular haemorrhage, IVH) was evaluated in multivariable
      regression models. RESULTS: No significant associations were evident between
      temperature parameters and clinical parameters and haematoma volume (with and
      without IVH), even after adjustment for key prognostic factors. CONCLUSIONS: No
      relationship was evident between ambient temperature and severity in acute ICH.

PMID- 24577384
TI  - Anti-diabetic effects of the Indian indigenous fruit Emblica officinalis Gaertn:
      active constituents and modes of action.
AB  - Dietary constituents are shown to play an important role in the development of
      diabetes. Studies have shown that the fruits of Emblica officinalis Gaertn or
      Phyllanthus emblica Linn, colloquially known as Indian gooseberry or amla and/or
      some of its important constituents (including gallic acid, gallotanin, ellagic
      acid and corilagin), possess anti-diabetic effects through their antioxidant and
      free radical scavenging properties. Amla has also been reported to prevent/reduce
      hyperglycemia, cardiac complications, diabetic nephropathy, neuropathy,
      cataractogenesis and protein wasting. However, clinical trial data with human
      subjects are limited and preliminary. For the first time this review summarizes
      the anti-diabetic affects of amla and also addresses the mechanisms mediating
      these properties.

PMID- 24577385
TI  - Policies to aid the adoption of personalized medicine.

PMID- 24577386
TI  - Built-to-buy start-ups begin to bloom.

PMID- 24577391
TI  - Patentee bears burden of proof when licence agreements are questioned.

PMID- 24577390
TI  - Trial watch: global migration of clinical trials.

PMID- 24577392
TI  - Recent patents related to p53.

PMID- 24577393
TI  - An audience with...John Reed.

PMID- 24577394
TI  - Anticancer drugs: a clearer pathway view.

PMID- 24577396
TI  - Antibody engineering: fine-tuning antibody-drug conjugates.

PMID- 24577403
TI  - Truncated-correlation photothermal coherence tomography of artificially
      demineralized animal bones: two- and three-dimensional markers for mineral loss
      monitoring.
AB  - The challenge of depth-resolved, nonionizing (hybrid-optical) detection of
      mineral loss in bones is addressed using truncated-correlation photothermal
      coherence tomography (TC-PCT). This approach has importance not only in ground
      based clinical procedures, but also in microgravity space applications. Analogous
      to x-ray morphometric parameters, two- and three-dimensional markers have been
      defined and estimated for chemically demineralized goat rib bones. Cortical and
      trabecular regions have been analyzed independently and together using the
      computational slicing advantage of TC-PCT, and the results have been verified
      using micro-CT imaging (the gold standard). For low-demineralization levels, both
      modalities follow the same trend. However, for very high mineral loss that is
      unlikely to occur naturally, anomalies exist in both methods. Demineralization
      tracking has been carried out to a depth of ~3  mm below the irradiated surface.
      Compared with micro-CT imaging, TC-PCT offers an improved dynamic range, which is
      a beneficial feature while analyzing highly demineralized bones. Also, TC-PCT
      parameters are found to be more sensitive to trabecular and combined cortical
      trabecular demineralization compared with x-ray parameters. Axial and lateral
      resolutions in bone imaging for the current instrumental configuration are ~25
      and 100 MUm, respectively.

PMID- 24577401
TI  - REV-ERB and ROR nuclear receptors as drug targets.
AB  - The nuclear receptors REV-ERB (consisting of REV-ERBalpha and REV-ERBbeta) and
      retinoic acid receptor-related orphan receptors (RORs; consisting of RORalpha,
      RORbeta and RORgamma) are involved in many physiological processes, including
      regulation of metabolism, development and immunity as well as the circadian
      rhythm. The recent characterization of endogenous ligands for these former orphan
      nuclear receptors has stimulated the development of synthetic ligands and opened
      up the possibility of targeting these receptors to treat several diseases,
      including diabetes, atherosclerosis, autoimmunity and cancer. This Review focuses
      on the latest developments in ROR and REV-ERB pharmacology indicating that these
      nuclear receptors are druggable targets and that ligands targeting these
      receptors may be useful in the treatment of several disorders. 

PMID- 24577404
TI  - Regional difference of inflammatory acne lesions according to beta-defensin-2
      expression.

PMID- 24577400
TI  - Targeting tumour-supportive cellular machineries in anticancer drug development.
AB  - Traditional anticancer chemotherapeutics targeting DNA replication and cell
      division have severe side effects, but they have proved to be highly successful
      in treating some cancers. Drugs targeting signalling oncoproteins that have
      gained tumour-driving functions through mutations or overexpression were
      subsequently developed to increase specificity and thus reduce side effects, but
      have limitations such as the development of resistance. Now, a new wave of small
      molecule anticancer agents is emerging, targeting complex multicomponent cellular
      machineries - including chromatin modifiers, heat shock protein chaperones and
      the proteasome - which thus interfere with those support systems that are more
      essential for cancer cells than for normal cells. Here, we provide our
      perspective on the advantages and limitations of agents that target tumour
      supportive cellular machineries (other than those involving DNA replication),
      comparing them with agents that target signalling intermediates. 

PMID- 24577405
TI  - Nectin-4 mutations causing ectodermal dysplasia with syndactyly perturb the rac1
      pathway and the kinetics of adherens junction formation.
AB  - Defective nectin-1 and -4 have been implicated in ectodermal dysplasia (ED)
      syndromes with variably associated features including orofacial and limb defects.
      In particular, nectin-1 mutations cause cleft lip/palate ED (CLPED1;
      OMIM#225060), whereas defective nectin-4 is associated with ED-syndactyly
      syndrome (EDSS1; OMIM#613573). Although the broad phenotypic overlap suggests a
      common mode of action of nectin-1 and -4, little is known about the pathogenic
      mechanisms involved. We report the identification of, to our knowledge, a
      previously undescribed nectin-4 homozygous p.Val242Met missense mutation in a
      patient with EDSS1. We used patient skin biopsy and primary keratinocytes, as
      well as nectin-4 ectopic expression in epithelial cell lines, to characterize
      functional consequences of p.Val242Met and p.Thr185Met mutations, the latter
      previously identified in compound heterozygosity with a truncating mutation. We
      show that nectin-4-altered expression perturbs nectin-1 clustering at
      keratinocyte contact sites and delays, but does not impede cell-cell aggregation
      and cadherin recruitment at adherens junctions (AJs). Moreover, trans-interaction
      of nectin-1 and -4 induces the activation of Rac1, a member of the Rho family of
      small GTPases, and regulates E-cadherin-mediated cell-cell adhesion. These data
      outline a synergistic action of nectin-1 and -4 in the early steps of AJ
      formation and implicate this interaction in modulating the Rac1 signaling
      pathway. 

PMID- 24577406
TI  - Mechanisms of natural gene therapy in dystrophic epidermolysis bullosa.
AB  - Revertant mosaicism has been reported in several inherited diseases, including
      the genetic skin fragility disorder epidermolysis bullosa (EB). Here, we describe
      the largest cohort of seven patients with revertant mosaicism and dystrophic EB
      (DEB), associated with mutations in the COL7A1 gene, and determine the underlying
      molecular mechanisms. We show that revertant mosaicism occurs both in autosomal
      dominantly and recessively inherited DEB. We found that null mutations resulting
      in complete loss of collagen VII and severe disease, as well as missense or
      splice-site mutations associated with some preserved collagen VII function and a
      milder phenotype, were corrected by revertant mosaicism. The mutation, subtype,
      and severity of the disease are thus not decisive for the presence of revertant
      mosaicism. Although collagen VII is synthesized and secreted by both
      keratinocytes and fibroblasts, evidence for reversion was only found in
      keratinocytes. The reversion mechanisms included back mutations/mitotic
      recombinations in 70% of the cases and second-site mutations affecting splicing
      in 30%. We conclude that revertant mosaicism is more common than previously
      assumed in patients with DEB, and our findings will have implications for future
      therapeutic strategies using the patient's naturally corrected cells as a source
      for cell-based therapies. 

PMID- 24577402
TI  - Drugging the p53 pathway: understanding the route to clinical efficacy.
AB  - The tumour suppressor p53 is the most frequently mutated gene in human cancer,
      with more than half of all human tumours carrying mutations in this particular
      gene. Intense efforts to develop drugs that could activate or restore the p53
      pathway have now reached clinical trials. The first clinical results with
      inhibitors of MDM2, a negative regulator of p53, have shown efficacy but hint at
      on-target toxicities. Here, we describe the current state of the development of
      p53 pathway modulators and new pathway targets that have emerged. The challenge
      of targeting protein-protein interactions and a fragile mutant transcription
      factor has stimulated many exciting new approaches to drug discovery. 

PMID- 24577407
TI  - beta-arrestin 2 inhibits proinflammatory chemokine production and attenuates
      contact allergic inflammation in the skin.
AB  - beta-Arrestins participate in G-protein receptor signaling and act as adapter
      proteins that direct the recruitment, activation, and scaffolding of various
      cytoplasmic signaling complexes. beta-Arrestin 2-deficient (Arrb2(-/-)) mice show
      decreased T-cell recruitment into allergic lung tissue but increased neutrophil
      infiltration into wounded skin. Given these opposing effects in different immune
      cell subsets, we investigated the role of beta-arrestin 2 in the regulation of
      contact hypersensitivity responses. We observed significantly increased allergic
      ear swelling to the obligate contact sensitizers DNFB and FITC in Arrb2(-/-)
      compared with wild-type mice. Immunohistological analyses revealed strikingly
      increased neutrophil infiltration with abundant subcorneal pustules in inflamed
      ear tissue of DNFB-allergic Arrb2(-/-) mice. Experiments involving adoptive
      transfers of sensitized lymphocytes and bone marrow chimeric mice indicated that
      beta-arrestin 2 exerts its anti-inflammatory effects predominantly through
      radioresistant, skin-resident cells in the challenge phase of contact
      hypersensitivity. As a potential mechanism, we found that primary cultures of
      beta-arrestin 2-deficient keratinocytes secreted higher levels of neutrophil
      attracting chemokines including CXCL1/KC in response to T cell-derived cytokines
      in vitro. These experimental results support a model in which beta-arrestin 2
      inhibits the production of proinflammatory chemokines, which limits the
      recruitment of myeloid immune cells and thereby attenuates allergic skin
      inflammation. 

PMID- 24577409
TI  - Effects of lifestyle-related interventions on blood pressure in low and middle
      income countries: systematic review and meta-analysis.
AB  - Despite the overwhelming evidence supporting the effectiveness of
      antihypertensive medication, hypertension remains poorly controlled in low and
      middle-income countries (LMICs). Lifestyle intervention studies reporting effects
      on blood pressure published from January 1977 to September 2012 were searched on
      various databases. From the 6211 references identified, 52 were included in the
      systematic review (12, 024 participants) and 43 were included in the meta
      analysis (in total 6779 participants). We calculated and pooled effect sizes in
      mmHg with random-effects models. We grouped interventions into behavioral
      counseling (1831 participants), dietary modification (1831 participants),
      physical activity (1014 participants) and multiple interventions (2103
      participants). Subgroup analysis and meta-regression were used to evaluate
      origins of heterogeneity. Lifestyle interventions significantly lowered blood
      pressure levels in LMIC populations, including in total 6779 participants. The
      changes achieved in SBP (95% confidence interval) were: behavioral counseling 
      5.4 (-10.7, -0.0) mmHg, for dietary modification -3.5 (-5.4, -1.5) mmHg, for
      physical activity -11.4 (-16.0, -6.7) mmHg and for multiple interventions -6.0 (
      8.9, -3.3) mmHg. The heterogeneity was high across studies and the quality was
      generally low. Subgroup analyses showed smaller samples reporting larger effect
      sizes; intervention lasting less than 6 months showed larger effect sizes and
      intention-to-treat analysis showed smaller effect sizes Lifestyle interventions
      may be of value in preventing and reducing blood pressure in LMICs. Nevertheless,
      the overall quality and sample size of the studies included were low.
      Improvements in the size and quality of studies evaluating lifestyle
      interventions are required.

PMID- 24577408
TI  - Histamine contributes to tissue remodeling via periostin expression.
AB  - Histamine is thought to have a critical role in the synthesis of extracellular
      matrix in skin and may be involved in tissue remodeling of allergic diseases.
      Recent studies revealed that periostin, a matricelluar protein, contributed to
      tissue remodeling; however, a link between periostin and histamine remains
      unproven. We investigated whether periostin was involved in histamine-induced
      collagen production. Cultured dermal fibroblasts derived from wild-type (WT) or
      periostin knockout (PN(-/-)) mice were stimulated with histamine, and then
      collagen and periostin production was evaluated. Histamine induced collagen gene
      expression in WT fibroblasts in the late phase but not in the early phase,
      whereas no effect on collagen expression was observed in histamine-stimulated PN(
      /-) fibroblasts. In WT fibroblasts, histamine directly induced periostin
      expression in a dose-dependent manner, and an H1 receptor antagonist blocked both
      periostin and collagen expression. Histamine activated extracellular signal
      regulated kinase 1/2 (ERK1/2) through the H1 receptor. Periostin induction was
      inhibited by either H1 antagonist or ERK1/2 inhibitor treatment in vitro and was
      attenuated in H1R(-/-) mice. Elevated expression of periostin was found in
      lesional skin from atopic dermatitis patients. These results suggest that
      histamine mediates periostin induction and collagen production through activation
      of the H1 receptor-mediated ERK1/2 pathway; furthermore, histamine may accelerate
      the chronicity of atopic dermatitis. 

PMID- 24577411
TI  - Hypertension, alcohol drinking and stroke incidence: a population-based
      prospective cohort study among inner Mongolians in China.
AB  - OBJECTIVES: The purpose of this study was to evaluate the effect of hypertension
      and alcohol drinking on stroke incidence and whether alcohol drinking would
      increase the risk of stroke in hypertension participants among Inner Mongolians.
      METHODS: A prospective cohort study from June 2003 to July 2012 was conducted
      among 2535 people aged 20 years and older from Inner Mongolia, China. We
      categorized the participants into four subgroups according to blood pressure and
      drinking status. The cumulative risks of stroke among the four subgroups were
      estimated with the Kaplan-Meier curves and compared by log-rank test. Cox
      proportional hazards models and receiver operating characteristic (ROC) curves
      were employed to evaluate the association between hypertension, alcohol drinking
      and stroke incidence. RESULTS: A total of 120 stroke patients were observed
      during the follow-up period. The multivariate-adjusted hazard ratios (95%
      confidential intervals) of stroke for nonhypertension/drinkers,
      hypertension/nondrinkers and hypertension/drinkers were 1.03 (0.48-2.22), 2.64
      (1.45-4.81) and 2.89 (1.55-5.39), respectively, compared with
      nonhypertension/nondrinkers. The area under ROC curve (AUC) for a model
      containing hypertension and drinking status along with conventional factors (AUC
      = 0.684) was significantly (P = 0.005) larger than one containing only
      conventional factors (AUC = 0.660). CONCLUSION: These findings suggest that
      hypertension is an independent risk factor of stroke in Inner Mongolians.
      Drinkers with hypertension seem to be more susceptible to stroke; larger-sample
      prospective cohort studies are still required to examine the cumulative effect of
      drinking and hypertension on stroke incidence.

PMID- 24577412
TI  - Palladium-catalyzed intermolecular Heck reaction of alkyl halides.
AB  - Intermolecular Heck reaction of common alkyl halides, a longstanding problem in
      palladium catalysis, is realized with a simple Pd/dppf catalyst. Both primary and
      secondary alkyl halides are suitable for coupling with aromatic olefins. Single
      electron transfer from (dppf)Pd(0) to alkyl halide initiated the catalytic cycle
      and gave alkyl radicals. 

PMID- 24577413
TI  - Megacystis-microcolon-intestinal hypoperistalsis syndrome: case report and review
      of prenatal ultrasonographic findings.
AB  - OBJECTIVE: To investigate prenatal ultrasonographic findings associated with
      megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS). METHODS: A
      PubMed search was performed using the terms 'MMIHS', 'MMIH' and 'prenatal
      diagnosis'. RESULTS: A total of 50 cases were analyzed. Prenatal diagnosis was
      achieved in 26% of cases. In 54% of patients with a correct antenatal diagnosis
      there was a previously affected sibling. Fetal megacystis with or without
      hydroureteronephrosis was the most common initial ultrasonographic finding (88%).
      While megacystis eventually complicated all fetal presentations, isolated
      bilateral hydronephrosis and isolated dilated stomach were noted (in 10 and 2% of
      cases, respectively) prior to megacystis. The initial sonographic abnormality was
      most commonly detected (in 70% of patients) in the second trimester. Amniotic
      fluid was normal in 69% and increased in 27% of cases. Gastrointestinal
      abnormalities were noted in 24% of pregnancies. CONCLUSION: MMIHS should be
      prenatally suspected when fetal megacystis is associated with a normal or
      increased amount of amniotic fluid and normal external genitalia, especially in
      the setting of a suggestive family history. Associated gastrointestinal findings
      support this diagnosis. Isolated bilateral hydronephrosis may precede the
      development of megacystis. Due to preserved renal function and a general absence
      of oligohydramnios, no rationale exists for vesicoamniotic shunt placement.

PMID- 24577414
TI  - Effect of amniotic membrane proteins in human cancer cell lines: an exploratory
      study.
AB  - Human amniotic membrane (hAM) has recently drawn attention as an upcoming anti
      cancer therapy. Regarding the strategies which have already investigated, little
      is known about hAM protein extracts (hAMPE) effect on cancer. So, this work aims
      to study the effect of hAMPE in metabolic activity of several human cancer cell
      lines. hAMPE were mechanically obtained, thus avoiding the effect of detergents
      and other reagents commonly used in protein extraction under the cell lines
      studied. After quantification of proteins in hAMPE, their effect on the metabolic
      activity of 21 human cancer cell lines was assessed by 3-(4,5-dimethylthia-zolyl
      2)2,5-diphenyltetrazolium bromide (MTT) assay. Our results indicate that there is
      an inhibition of metabolic activity until 25 and 50% in two and seven cell lines,
      respectively. Five cell lines proved to be very sensitive to hAMPE, being its
      metabolic activity more than 50% inhibited. Our results show that hAMPE can
      inhibit the metabolic activity of some human cancer cell lines. However, research
      about this cell line-dependent response to hAMPE becomes indispensable.

PMID- 24577410
TI  - Cardiovascular risk assessment in low-resource settings: a consensus document of
      the European Society of Hypertension Working Group on Hypertension and
      Cardiovascular Risk in Low Resource Settings.
AB  - The Global Burden of Diseases, Injuries, and Risk Factors Study 2010 confirms
      ischemic heart disease and stroke as the leading cause of death and that
      hypertension is the main associated risk factor worldwide. How best to respond to
      the rising prevalence of hypertension in resource-deprived settings is a topic of
      ongoing public-health debate and discussion. In low-income and middle-income
      countries, socioeconomic inequality and cultural factors play a role both in the
      development of risk factors and in the access to care. In Europe, cultural
      barriers and poor communication between health systems and migrants may limit
      migrants from receiving appropriate prevention, diagnosis, and treatment. To use
      more efficiently resources available and to make treatment cost-effective at the
      patient level, cardiovascular risk approach is now recommended. In 2011, The
      European Society of Hypertension established a Working Group on 'Hypertension and
      Cardiovascular risk in low resource settings', which brought together
      cardiologists, diabetologists, nephrologists, clinical trialists,
      epidemiologists, economists, and other stakeholders to review current strategies
      for cardiovascular risk assessment in population studies in low-income and middle
      income countries, their limitations, possible improvements, and future interests
      in screening programs. This report summarizes current evidence and presents
      highlights of unmet needs. 

PMID- 24577415
TI  - The effect of pH on the electrical capacitance of phosphatidylcholine
      phosphatidylserine system in bilayer lipid membrane.
AB  - This paper reports measurements on the pH dependence of the electrical
      capacitance of lipid membranes formed by 1:1 phosphatidylcholine
      phosphatidylserine mixtures. A theoretical model was developed to describe this
      dependence, in which the contributions of functional groups (as the active
      centers of adsorption of the hydrogen and hydroxide ions) to the overall membrane
      capacitance were assumed to be additive. The proposed model was verified
      experimentally using electrochemical impedance spectroscopy. The theoretical
      predictions agreed with the experimental results over the measured pH range. A
      minimum corresponding to the isoelectric point appeared in both the theoretical
      equation and the experimental data. 

PMID- 24577416
TI  - Synergistic toughening of hard, nacre-mimetic MoSi2 coatings by self-assembled
      hierarchical structure.
AB  - Like many other intermetallic materials, MoSi2 coatings are typically hard, but
      prone to catastrophic failure due to their low toughness at ambient temperature.
      In this paper, a self-assembled hierarchical structure that closely resembles
      that of nacre (i.e., mother of pearl) was developed in a MoSi2-based coating
      through a simple, yet cost-effective, depostion technique. The newly formed
      coating is tough and can withstand multiple indentations at high loads. Key
      design features responsible for this remarkable outcome were identified. They
      include a functionally graded multilayer featuring elastic modulus oscillation,
      varying sublayer thickness and a columnar structure that are able to attenuate
      stress concentrations; interlocking boundaries between adjacent sublayers that
      improve the bonding and arrest the cracks; a transitional layer that bridges the
      coating and substrate and facilitates load transfer. Moreover, the contributions
      of six important structural characteristics to damage resistance are quantified
      using finite elemnet analysis and in an additive manner (i.e., from low- to high
      level complexity). The in-situ toughened coating is envisaged to enhance the
      mechanical performance and extend the lifespan of metal components used in safety
      critical applications. 

PMID- 24577417
TI  - A case of gray platelet syndrome masked by immune thrombocytopenia at
      presentation.
AB  - We report a case of gray platelet syndrome (GPS) associated with immune
      thrombocytopenia (ITP) at presentation. A 22-year-old male patient presenting
      with petechiae on his limbs was diagnosed with ITP due to a gradual decrease of
      his platelet count to a minimum of 26 * 10(9) /liter and an elevated platelet
      associated IgG (PA-IgG) level in the absence of any other specific cause of
      thrombocytopenia. Administration of prednisolone increased his platelet count,
      but this dropped again to approximately 50 * 10(9) /liter as the dose was
      tapered, and remained at the same level after the treatment was terminated.
      Thirteen years later, we reassessed the cause of the thrombocytopenia because the
      PA-IgG level was found to be within the normal range. There were large
      hypogranular platelets on the blood film and a deficit of alpha-granules in the
      platelets on electron microscopy. On this basis, we diagnosed his
      thrombocytopenia as GPS. To our knowledge, this is the first report of a GPS case
      associated with ITP at presentation. This case illustrates the importance of
      carefully reviewing blood film results in the differential diagnosis of
      thrombocytopenia.

PMID- 24577418
TI  - "The El Greco fallacy" fallacy.
AB  - To what extent does an artist's work represent his or her perceptual world, and
      to what extent can attributes of his or her work be ascribed to sensory defects?
      These issues lie at the center of a conjecture more than a century old, which has
      been termed the El Greco fallacy. The El Greco fallacy posits that the elongation
      evident in El Greco's art reflects an underlying perceptual elongation of objects
      caused by astigmatism. The "logical" refutation of this theory argues that any
      perceptual elongation that El Greco might have experienced as a result of
      astigmatism would have caused not only his subjects to be elongated but also his
      canvas. Hence, it should have been unnecessary for him to elongate his paintings
      to match his perception. This objection is important because it warns us against
      drawing the erroneous conclusion that an artist's work represents a facsimile of
      his or her perception. However, an analysis of the effects of astigmatism on the
      retinal image suggests that this "logical" refutation of the El Greco fallacy
      promulgates another fallacy--that of astigmatism as a source of a constant
      perceptual error.

PMID- 24577419
TI  - Periacetabular bone metabolism following hip revision surgery. PET-based
      evaluation of allograft osteointegration.
AB  - The treatment of loosened total hip replacement (THR) acetabular components may
      require the management of severe bone defects. Although being applied for
      decades, there is only limited scientific data about the osteointegration of
      cancellous bone allografts (CBA) and other void fillers. Monitoring of
      periprosthetic bone regeneration could possibly help to optimize this process
      thereby reducing late failure rates. The aim of this study was to show
      osteometabolic changes in periprosthetic CBA after THR revision with the use of
      sodium-[18F]-fluoride (NaF) and positron emission tomography (PET). PATIENTS,
      METHODS: Twelve patients undergoing THR revision with the use of CBA were
      prospectively enrolled in the study. Nine patients completed all necessary
      examinations and were included in the evaluation. The temporal pattern of
      osteointegration was assessed via NaF-PET at one (PET1) and six weeks (PET2)
      after surgery. CBA, tantalum implants, supraacetabular regions ipsilateral and
      contralateral, and parasymphyseal pubic bones were delineated as volumes of
      interest (VOI) in postop CT scans, which were then merged with the PET data.
      RESULTS: In comparison to the contralateral supraacetabular reference bone, a
      significant 1.5-fold increase of osteometabolic activity from PET1 to PET2 was
      seen in the CBA region. Also, the ipsilateral supraacetabular host bone showed a
      higher NaF-influx in week 6, compared to the first postoperative week. The
      supraacetabular site exhibited a significantly 1.8- to 2-fold higher influx and
      uptake than bone regions in non-operated sites. Tantalum implants had a low NaF
      influx at both time points investigated. CONCLUSION: Using NaF-PET osteometabolic
      changes of CBA and implant-bone-interfaces can be monitored. Applying this method
      we demonstrated early periprosthetic temporal bone regeneration patterns in THR
      cup revision patients.

PMID- 24577423
TI  - Pap, gruel, and panada: early approaches to artificial infant feeding.
AB  - This paper collects information on artificial infant feeding published before
      1860, the year when commercial formula became available. We have extensive
      artifactual evidence of thousands of feeding vessels since the Bronze Age.
      Special museum collections can be found in London, Paris, Cologne, Fecamp,
      Toronto, New Mexico, and elsewhere. The literature on the use of animal milk for
      infant feeding begins with Soranus in the 2nd century CE. Literature evidence
      from the very first printed books in the 15th century proves that physicians,
      surgeons, midwives, and the laity were aware of the opportunities and risks of
      artificial infant feeding. Most 17th to 19th century books on infant care
      contained detailed recipes for one or several of the following infant foods: pap,
      a semisolid food made of flour or bread crumbs cooked in water with or without
      milk; gruel, a thin porridge resulting from boiling cereal in water or milk, and
      panada, a preparation of various cereals or bread cooked in broth. During the
      18th century, the published opinion on artificial feeding evolved from health
      concerns to a moral ideology. This view ignored the social and economic pressures
      which forced many mothers to forego or shorten breast-feeding. Bottle-feeding has
      been common practice throughout history.

PMID- 24577424
TI  - Injury of the spinothalamic tract in a patient with mild traumatic brain injury:
      diffusion tensor tractography study.
AB  - OBJECTIVE: To report on a patient found to have injury of the spinothalamic tract
      on diffusion tensor tractography following traumatic brain injury. CASE
      DESCRIPTION: A 29-year-old male patient with head trauma resulting from a
      pedestrian car accident presented with pain in multiple areas (both subscapular
      areas, posterior head and neck, both upper trapezius areas, and the right arm and
      leg). His pain had not improved with various types of conservative management.
      RESULTS: Evaluations (conventional brain magnetic resonance imaging,
      electromyography, and whole spine magnetic resonance imaging), performed 2 years
      after the head trauma, did not reveal any specific abnormality. Fibromyalgia and
      myofascial pain syndrome were ruled out by physical examination. Injuries of the
      spinothalamic tracts in both hemispheres were observed on diffusion tensor
      imaging in terms of the configuration (thinning) and diffusion tensor
      tractography parameters (decreased fractional anisotropy or tract volume).
      CONCLUSION: Some of the pain in the trunk and extremities in this patient could
      be ascribed to central pain caused by injury of both spinothalamic tracts. We
      conclude that diffusion tensor tractography provides a useful means of detecting
      injury of the spinothalamic tract in patients with traumatic brain injury.

PMID- 24577426
TI  - Use of ketamine for control of refractory seizures during the intraoperative
      period.

PMID- 24577427
TI  - Latent factor deficiency in the setting of an acute subdural hematoma.

PMID- 24577425
TI  - High- and low-affinity sites for sodium in delta-OR-Gi1alpha (Cys (351)-Ile
      (351)) fusion protein stably expressed in HEK293 cells; functional significance
      and correlation with biophysical state of plasma membrane.
AB  - The effect of sodium, potassium, and lithium on delta-opioid receptor ligand
      binding parameters and coupling with the cognate G proteins was compared in model
      HEK293 cell line stably expressing PTX-insensitive delta-OR-Gi1alpha (Cys(351)
      Ile(351)) fusion protein. Agonist [(3)H]DADLE binding was decreased in the order
      Na(+) ? Li(+) > K(+) > (+)NMDG. When plotted as a function of increasing NaCl
      concentrations, the binding was best-fitted with a two-phase exponential decay
      considering two Na(+)-responsive sites (r (2) = 0.99). High-affinity Na(+)-sites
      were characterized by Kd = 7.9 mM and represented 25 % of the basal level
      determined in the absence of ions. The remaining 75 % represented the low
      affinity sites (Kd = 463 mM). Inhibition of [(3)H]DADLE binding by lithium,
      potassium, and (+)-NMDG proceeded in low-affinity manner only. Surprisingly, the
      affinity/potency of DADLE-stimulated [(35)S]GTPgammaS binding was increased in a
      reverse order: Na(+) < K(+) < Li(+). This result was demonstrated in PTX-treated
      as well as PTX-untreated cells. Therefore, it is not restricted to
      Gi1alpha(Cys(351)-Ile(351)) within the delta-OR-Gi1alpha fusion protein, but is
      also valid for stimulation of endogenous G proteins of Gi/Go family in HEK293
      cells. Biophysical studies of interaction of ions with polar head-group region of
      lipids using Laurdan generalized polarization indicated the low-affinity type of
      interaction only proceeding in the order: Cs(+) < K(+) < Na(+) < Li(+). The
      results are discussed in terms of interaction of Na(+), K(+) and Li(+) with the
      high- and low-affinity sites located in water-accessible part of delta-OR binding
      pocket. We also consider the role of negatively charged Cl(-), Br(-), and I(-)
      counter anions in inhibition of both [(3)H]DADLE and [(35)S]GTPgammaS binding. 

PMID- 24577428
TI  - Prognostic value of somatosensory-evoked potentials and CT scan evaluation in
      acute traumatic brain injury.
AB  - BACKGROUND: The aim of this study is to assess whether a complete analysis of all
      early cortical somatosensory-evoked potentials (SEPs) components and computed
      tomography (CT) scan features can provide a better prognostic measure than the
      early cortical component N20/P25 alone, in patients with severe head injury.
      MATERIALS AND METHODS: We studied 81 consecutive patients admitted to intensive
      care unit with diagnosis of severe head injury. All patients underwent
      neurophysiological assessment with SEPs and electroencephalography within the
      first 6 days after trauma. The marginal effect of each variable on Glasgow
      Outcome Scale score was evaluated by using univariate measures of association. We
      fit a cumulative logit model by maximum likelihood, and the partial effect of
      each variable was assessed by likelihood ratio test. We performed variable
      selection by forward stepwise, according to the Akaike information criterion.
      RESULTS: Our final cumulative logit model including SEPs primary complex
      (pN20/fP20/cP22), SEPs middle latency (N30/P45/N60), and CT scan hypodensity
      values showed a significantly increased predictive power of Glasgow Outcome
      Scale, compared with pN20 alone (P<0.0001). CONCLUSIONS: Statistical analysis
      revealed a highly significant (P<0.0001) improvement in outcome prediction when
      the model includes a pool of amplitudes and latencies referred to different early
      evoked components pN20, pP25, fP20, cP22, N30, P45, and N60, associated to CT
      scan hypodensity values, compared with the use of the cortical parietal N20/P25
      alone.

PMID- 24577429
TI  - Gene expression pattern for putative chloroplast localized COPII related proteins
      with emphasis on Rab related proteins.
AB  - Vesicle transport occurs in the cytosol through COPI, COPII and a clathrin coated
      vesicle system for transport of lipids and proteins to different subcellular
      compartments. All three systems consist of several different protein components
      to maintain a functional transport. In chloroplasts photosynthesis takes place in
      thylakoids. Thylakoids contain a large amount of lipids and proteins but none of
      these components are produced there. Transport of lipids occurs from the envelope
      membrane where they are produced and through the aqueous stroma before being
      directed to the thylakoids. Nuclear encoded proteins use distinct pathways for
      entering thylakoids after import into chloroplasts. Transport of lipids through
      stroma requires either lipid transfer proteins, association between the envelope
      and the thylakoid membrane, or a vesicle transport system similar to the
      cytosolic one. No evidence exists for lipid transfer proteins in chloroplasts,
      nor for a consistent association between the envelope and the thylakoid membrane.
      However, vesicle transport has support from e.g., biochemical and genetics data
      as well as transelectron microscopy data. Moreover, a recent bioinformatics study
      revealed putatively COPII related proteins to be chloroplast localized in
      Arabidopsis and thus function in vesicle transport in chloroplasts. Here we
      present gene expression profiles of these putatively COPII related chloroplast
      localized proteins using Genevestigator (https://www.genevestigator.com/gv/) with
      special emphasis on Rab related proteins since they represent several stage of
      vesicle transport e.g., uncoating, tethering and fusion. 

PMID- 24577431
TI  - Persistence of noncancer-related musculoskeletal chronic pain among community
      dwelling older people: a population-based longitudinal study in Finland.
AB  - OBJECTIVE: To determine the persistence of chronic pain among community-dwelling
      older persons and to identify factors related to persistent chronic pain.
      METHODS: In this prospective longitudinal study, a random sample of Finnish
      community-dwelling people aged 76 years and older (n=256) were interviewed
      annually by a trained nurse at 3 time points. Data on prevalence, duration,
      location, and intensity of musculoskeletal pain, analgesic use, demographics, and
      health characteristics were collected during the interviews. RESULTS: Chronic
      pain was reported by 48.9% of the participants at baseline, with 74.4% of them
      experiencing persistent chronic pain, that is, they reported chronic pain at all
      3 study points. Persistent chronic pain was associated with poor self-rated
      health (adjusted odds ratio [AOR]=2.26, 95% confidence interval [95% CI] 1.03
      4.98), mobility difficulties (AOR=2.80, 95% CI, 1.22-6.43), and arthrosis or
      rheumatoid arthritis (AOR=3.07, 95% CI, 1.47-6.42) when compared with persons
      without chronic pain. However, only 15% of the persons with persistent chronic
      pain were using analgesics on a regular basis, and one out of every 5 was not
      taking any analgesics. CONCLUSIONS: Chronic musculoskeletal pain is a highly
      persistent condition among community-dwelling older persons and it is related to
      poor health and mobility difficulties. In addition, the use of daily analgesic is
      low despite the continuous nature of chronic pain.

PMID- 24577433
TI  - Impact of race on male predisposition to birth asphyxia.
AB  - OBJECTIVE: To examine the associations of: (a) neonatal sex with mild-to-moderate
      and severe birth asphyxia, (b) fetal sex with mortality due to birth asphyxia and
      (c) neonatal race with severe birth asphyxia. STUDY DESIGN: We used the
      Nationwide Inpatient Sample (NIS) Database including the years 1993 to 2008 or
      its pediatric sub portion Kid's Inpatient Database (KID) for the years 1997,
      2000, 2003 and 2006. NIS database is collected annually from more than 1000
      hospitals across the United States for millions of inpatient discharge summaries.
      We included newborns older than 36 weeks gestational age or more than 2500 g at
      birth. We excluded newborns with congenital heart disease, major congenital
      anomalies and chromosomal disorders. We compared birth asphyxia in males to
      females, and in each race compared with whites, and examined effect of sex in
      association with birth asphyxia within each race/ethnicity. RESULT: There were 9
      708 251 term infants (51.8% males) included in the study. There were 15 569
      newborns diagnosed with severe birth asphyxia (1.6 in 1000); of them 56.1% were
      males. Odds ratio (OR)to have severe birth asphyxia in male newborns was 1.16
      (confidence interval (CI): 1.12 to 1.20, P<0.001). Compared with Whites, African
      American newborns had more birth asphyxia, OR 1.23 (CI: 1.16 to 1.31, P<0001),
      whereas Hispanics and Asians had less birth asphyxia. Native American newborns
      did not differ from their white counterparts. On comparing males to females
      within each race, male sex was associated with increased birth asphyxia in all
      races but Native American. CONCLUSION: Male sex and African-American race were
      associated with increased prevalence of birth asphyxia.

PMID- 24577430
TI  - Patterns of care for craniopharyngioma: survey of members of the american
      association of neurological surgeons.
AB  - BACKGROUND: Initial therapy for craniopharyngioma remains controversial.
      Population-based datasets indicate that traditional algorithms [gross total
      resection (GTR) vs. subtotal resection (STR) +/- radiation therapy (XRT)] are
      often not employed. We investigated neurosurgical practice patterns. METHODS: A
      ten-question survey was electronically distributed to members of the American
      Association of Neurological Surgeons. Responses were analyzed using standard
      statistical techniques. RESULTS: 102 responses were collected, with a median of
      25 craniopharyngiomas managed per respondent. 36% estimated that their practice
      included >=75% pediatric patients and 61% had an academic practice. 36% would
      recommend observation or XRT for a suspected craniopharyngioma in the absence of
      a tissue diagnosis, with 46% of these indicating this recommendation in >=10% of
      the cases. Following STR, 35% always recommend XRT and 59% recommend it in over
      half of the cases. However, following STR or biopsy alone, 18 and 11% never
      recommend XRT. There was no association between the type of practice (i.e.
      academic or >=75% pediatric patients) and practice patterns. CONCLUSIONS: This
      survey verifies that a deviation from established algorithms is common,
      underscoring the clinical complexity of these patients and recent secondary data
      analyses. This should influence clinical researchers to investigate outcomes for
      patients treated using alternative methods. It will lend insight into appropriate
      treatment options and contribute to quality of life outcomes studies for
      craniopharyngioma.

PMID- 24577432
TI  - High oleic/stearic fatty-acid desaturation index in cord plasma from infants of
      mothers with gestational diabetes.
AB  - OBJECTIVE: Enhanced fatty-acid desaturation by stearoyl-CoA desaturase enzyme-1
      (SCD1) is associated with obesity. This study determined desaturation in the cord
      plasma of newborns of mothers with and without gestational diabetes (GDM). STUDY
      DESIGN: Newborns of mothers with GDM (n=21) and without (control, n=22) were
      recruited. Cord plasma fatty-acid desaturation indices (palmitoleic/palmitic,
      oleic/stearic ratios) were compared, and correlated with anthropometrics and
      biochemical measures. A subset of very low-density lipoprotein (VLDL)
      desaturation indices were determined to approximate the liver SCD1 activity.
      RESULT: The total oleic/stearic index was higher in GDM, despite adjustment for
      cord glucose concentrations. Among GDM and controls, the oleic/stearic index
      correlated with cord glucose concentrations (rs=0.36, P=0.02). Both
      palmitoleic/palmitic and oleic/stearic indices correlated with waist
      circumference (r=0.47, P=0.001; r=0.37, P=0.01). The VLDL oleic/stearic index was
      higher in GDM. CONCLUSION: The elevated total oleic/stearic index suggests
      increased lipogenesis in GDM newborns. Factors in addition to glucose supply may
      influence fetal SCD1 activity.

PMID- 24577434
TI  - Prediction of excessive gestational weight gain from week-specific cutoff values:
      a cohort study.
AB  - OBJECTIVE: To assess the prognostic validity of the Institute of
      Medicine/National Research Council (IOM/NRC) week-specific cutoff values for
      inadequate or excessive total gestational weight gain (GWG) by 4-week intervals.
      STUDY DESIGN: We merged data from two German cohorts (LMU cohort (all maternal
      weight categories) and PEACHES cohort (obese women)) to provide information on
      GWG for 749 women (365 normal weight, 199 overweight and 185 obese). We
      calculated the prognostic values for suboptimal and excessive GWG according to
      the IOM/NRC cutoff values. RESULT: The positive predictive values for excessive
      total GWG for those who experienced excessive GWG early in pregnancy was 70.1%
      (95% confidence interval (CI) 60.5; 78.6) as of week 12/1 to 16/0 in normal
      weight women, 89.5% (95% CI 75.2; 97.1) and 95.2 (76.2; 99.9) 95.2% (95% CI 76.2;
      99.9) as of week 8/1 to 12/0 for overweight and obese women, respectively. In
      absence of excessive GWG as of week 12/1 to 16/0, normal-weight women had 77.5%
      (95% CI 77.1; 83.1) probability of not experiencing excessive total GWG (negative
      predictive value). In overweight and obese women, the negative predictive value
      was considerably lower up to week 24/1 to 28/0 (60.0% (95% CI 48.8; 70.5) in week
      20/1 to 24/0 and 50.6% (95% CI 39.3; 61.9) in week 24/1 to 28/0). Most women with
      inadequate GWG in the first and second trimester had adequate total final GWG
      (positive predictive value for total inadequate GWG <50% up to week 16/1 to 20/0
      in all groups). CONCLUSION: As women with excessive weight gain can be identified
      with high confidence if the GWG exceeds the IOM/NRC week-specific cutoff values,
      interventions may be initiated early in pregnancy.

PMID- 24577435
TI  - Impact of premedication on neonatal intubations by pediatric and neonatal
      trainees.
AB  - OBJECTIVE: To determine if premedication and training level affect the success
      rates of neonatal intubations. STUDY DESIGN: We retrospectively reviewed a
      hospital-approved neonatal intubation database from 2003 to 2010. Intubation
      success rate was defined as the number of successful intubations divided by the
      total number of attempts, and then compared by trainee's experience level and the
      use of premedication. Premedication regimen included anticholinergic, analgesic
      and muscle relaxant agents. RESULT: There were 169 trainees who completed 1071
      successful intubations with 2694 attempts. The median success rate was 36% by all
      trainees, and improved with training level from 29% for pediatric trainees to 50%
      for neonatal trainees (P<0.001). Premedication was used in 58% of intubation
      attempts. The median success rate was double with premedication (43% versus 22%,
      P<0.001). CONCLUSION: Neonatal endotracheal intubation is a challenge for
      trainees. Intubation success rates progressively improve with experience.
      Premedication is associated with improved success rates for all training levels.

PMID- 24577436
TI  - Diagnostic ionizing radiation exposure in premature patients.
AB  - OBJECTIVE: Concern regarding the magnitude and consequences of diagnostic
      radiation exposure in premature infants in neonatal intensive care units (NICUs)
      has increased as survival of premature infants has improved. Radiation exposure
      is not often rigorously monitored in NICU patients. The purpose of this
      observational study was to quantify the amount of ionizing radiation exposure in
      infants <33 weeks gestational age and to identify the indications for diagnostic
      imaging. STUDY DESIGN: We conducted a retrospective review of 215 premature
      infants who were <33 weeks gestation and who received central venous line (CVL)
      placement during their NICU stay during the period from 2006 to 2011. Absorbed
      ionizing radiation was estimated using the method of Puch-Kapst and colleagues
      (2009) and compared with recommended radiation exposure limits. All infants were
      29.2+/-2.3 weeks (mean+/-s.d.) and 1262+/-433 g birth weight. RESULT: Subjects
      received 15+/-15 radiographs (4.4+/-2.9 for CVL placement, 5.7+/-9.8 for
      gastrointestinal (GI) evaluations and 5.2+/-9.3 for respiratory indications).
      Eleven infants (5.1%) received more than the maximum recommended radiation from
      radiographs (>1000 MUSv). Inclusion of fluoroscopic procedures increased to 26
      the number of infants (12.1%) who received more than the maximum recommended 1000
      MUSv. CONCLUSION: Ionizing radiation exposure that exceeded the recommended
      maximum in premature infants at high risk for long-term sequelae occurred in
      12.1% of infants who were <33 weeks gestation and who were cared for in our NICU
      over the past 5 years. CVL placement accounted for 22% of this radiation
      exposure. GI evaluations accounted for the greatest amount of ionizing radiation
      exposure. We suggest that the increased use of other imaging strategies may
      reduce total ionizing radiation exposure in this vulnerable population.

PMID- 24577437
TI  - CD117 (c-kit) expression on CD34+ cells participates in the cytogenetic response
      to imatinib in patients with chronic myeloid leukemia in the first chronic phase.
AB  - BACKGROUND: Chronic myeloid leukemia (CML) biology seemed to be perfectly
      explored especially at the beginning of the tyrosine kinase inhibitors era. Later
      years with imatinib and second-generation tyrosine kinase inhibitors showed a
      variety of resistance mechanisms and it became obvious that the bcr-abl chimeric
      gene is not the only enemy to fight. Some studies assumed the decreased rate of
      programmed cell death (apoptotic) to be the primary mechanism by which BCR-ABL
      affects expansion of the leukemic clone in CML. Therefore, the aim of this study
      was to investigate the role of c-kit inhibition in treatment response. METHODS:
      Cytogenetic analysis, real-time quantitative reverse-transcriptase polymerase
      chain reaction, flow-cytometric analysis and imatinib serum level quantification
      were applied. RESULTS: The percentage of CD34+ cells expressing c-kit (CD117)
      isolated from bone marrow samples of 54 CML patients treated with standard-dose
      imatinib was significantly lower among imatinib responders. The fraction of
      apoptotic CD34+CD117+ cells in this patient group was significantly higher than
      in nonresponders. CONCLUSION: To achieve optimal treatment response in CML
      patients, the elimination of CD34+CD117+ may be necessary through an apoptotic
      pathway.

PMID- 24577439
TI  - Regulatory T cells: mind control.

PMID- 24577440
TI  - Intra- and interspecific challenges modulate cortisol but not androgen levels in
      a year-round territorial damselfish.
AB  - Interactions between individuals of different species are commonplace in animal
      communities. Some behaviors displayed during these interspecific social
      interactions may be very similar to those displayed during intraspecific social
      interactions. However, whether functional analogies between intra- and
      interspecific behaviors translate at the proximate level into an overlap in their
      underlying endocrine mechanisms remains largely unknown. Because steroids both
      mediate social behaviors and respond to them, we approached this question by
      comparing the behavioral and steroid response of free-living dusky gregories
      (Stegastes nigricans) to standardized territorial intrusions (sTI) of either
      conspecific or heterospecific food competitors. Stegastes nigricans is a year
      round territorial fish that 'cultivates' the algae on which it feeds and is
      highly aggressive to both intra- and interspecific intruders. Behavioral
      differences between intra- and interspecific aggressive responses to sTI were
      marginal, and sTI tests caused an increase in cortisol levels that was positively
      related with the levels of aggression. In contrast, androgen levels did not
      increase in response to sTI, yet they showed a positive relationship with
      agonistic behavior. These results parallel a pattern that was first described for
      year-round territorial bird species. Furthermore, they suggest that changes in
      endocrine-hormone levels during territoriality might be independent of the
      species that induces the territorial response. 

PMID- 24577441
TI  - The role of the olfactory recess in olfactory airflow.
AB  - The olfactory recess - a blind pocket at the back of the nasal airway - is
      thought to play an important role in mammalian olfaction by sequestering air
      outside of the main airstream, thus giving odorants time to re-circulate. Several
      studies have shown that species with large olfactory recesses tend to have a well
      developed sense of smell. However, no study has investigated how the size of the
      olfactory recess relates to air circulation near the olfactory epithelium. Here
      we used a computer model of the nasal cavity from a bat (Carollia perspicillata)
      to test the hypothesis that a larger olfactory recess improves olfactory airflow.
      We predicted that during inhalation, models with an enlarged olfactory recess
      would have slower rates of flow through the olfactory region (i.e. the olfactory
      recess plus airspace around the olfactory epithelium), while during exhalation
      these models would have little to no flow through the olfactory recess. To test
      these predictions, we experimentally modified the size of the olfactory recess
      while holding the rest of the morphology constant. During inhalation, we found
      that an enlarged olfactory recess resulted in lower rates of flow in the
      olfactory region. Upon exhalation, air flowed through the olfactory recess at a
      lower rate in the model with an enlarged olfactory recess. Taken together, these
      results indicate that an enlarged olfactory recess improves olfactory airflow
      during both inhalation and exhalation. These findings add to our growing
      understanding of how the morphology of the nasal cavity may relate to function in
      this understudied region of the skull. 

PMID- 24577438
TI  - Pathological pain and the neuroimmune interface.
AB  - Reciprocal signalling between immunocompetent cells in the central nervous system
      (CNS) has emerged as a key phenomenon underpinning pathological and chronic pain
      mechanisms. Neuronal excitability can be powerfully enhanced both by classical
      neurotransmitters derived from neurons, and by immune mediators released from CNS
      resident microglia and astrocytes, and from infiltrating cells such as T cells.
      In this Review, we discuss the current understanding of the contribution of
      central immune mechanisms to pathological pain, and how the heterogeneous immune
      functions of different cells in the CNS could be harnessed to develop new
      therapeutics for pain control. Given the prevalence of chronic pain and the
      incomplete efficacy of current drugs--which focus on suppressing aberrant
      neuronal activity--new strategies to manipulate neuroimmune pain transmission
      hold considerable promise.

PMID- 24577442
TI  - Production of all female progeny: evidence for the presence of the male sex
      determination factor on the Y chromosome.
AB  - The red flour beetle, Tribolium castaneum, follows an XX (female) and XY (male)
      sex determination system. Maternal supply of the protein Transformer (Tra) is
      required for XX insects to follow the female pathway. The nature and source of
      the signal that regulates male sex determination in XY beetles are not known.
      Parental RNAi-aided knockdown in expression of tra masculinizes genetic females
      (XX) that are fertile. The virgin females mated with these masculinized genetic
      females produced all female progeny. We present the genetic evidence to show that
      the factor responsible for male sex determination is present on the Y chromosome.
      These data also suggest that the Y chromosome in T. castaneum is not required for
      male fertility. 

PMID- 24577444
TI  - A protocol and calibration method for accurate multi-camera field videography.
AB  - Stereo videography is a powerful technique for quantifying the kinematics and
      behavior of animals, but it can be challenging to use in an outdoor field
      setting. We here present a workflow and associated software for performing
      calibration of cameras placed in a field setting and estimating the accuracy of
      the resulting stereoscopic reconstructions. We demonstrate the workflow through
      example stereoscopic reconstructions of bat and bird flight. We provide software
      tools for planning experiments and processing the resulting calibrations that
      other researchers may use to calibrate their own cameras. Our field protocol can
      be deployed in a single afternoon, requiring only short video clips of light,
      portable calibration objects. 

PMID- 24577443
TI  - In vivo cranial bone strain and bite force in the agamid lizard Uromastyx geyri.
AB  - In vivo bone strain data are the most direct evidence of deformation and strain
      regimes in the vertebrate cranium during feeding and can provide important
      insights into skull morphology. Strain data have been collected during feeding
      across a wide range of mammals; in contrast, in vivo cranial bone strain data
      have been collected from few sauropsid taxa. Here we present bone strain data
      recorded from the jugal of the herbivorous agamid lizard Uromastyx geyri along
      with simultaneously recorded bite force. Principal and shear strain magnitudes in
      Uromastyx geyri were lower than cranial bone strains recorded in Alligator
      mississippiensis, but higher than those reported from herbivorous mammals. Our
      results suggest that variations in principal strain orientations in the facial
      skeleton are largely due to differences in feeding behavior and bite location,
      whereas food type has little impact on strain orientations. Furthermore, mean
      principal strain orientations differ between male and female Uromastyx during
      feeding, potentially because of sexual dimorphism in skull morphology. 

PMID- 24577445
TI  - Load-induced changes in bone stiffness and cancellous and cortical bone mass
      following tibial compression diminish with age in female mice.
AB  - The vertebrate skeleton is an adaptive structure that responds to mechanical
      stimuli by increasing bone mass under increased mechanical loads. Although
      experimental animal models have shown the anabolic cortical bone response to
      applied load decreases with age, no consensus exists regarding whether this
      adaptive mechanism is affected by age in cancellous bone, the tissue most
      impacted by age-related bone loss. We used an established murine in vivo tibial
      loading model to characterize the load-induced cancellous, cortical and whole
      bone responses to mechanical stimuli in growing and mature female mice at 6, 10
      and 16 weeks of age. The effects of applied load on tibial morphology and
      stiffness were determined using microcomputed tomography and in vivo bone strains
      measured at the medial tibial midshaft during applied loading. At all ages, 2
      weeks of applied load produced larger midshaft cortical cross-sectional
      properties (+13-72%) and greater cancellous bone volume (+21-107%) and thicker
      trabeculae (+31-68%) in the proximal metaphyses of the loaded tibiae. The
      relative anabolic response decreased from 6 to 16 weeks of age in both the
      cancellous and cortical envelopes. Load-induced tibial stresses decreased more in
      6-week-old mice following loading, which corresponded to increased in vivo tibial
      stiffness. Stiffness in the loaded tibiae of 16-week-old mice decreased despite
      moderately increased cortical cross-sectional geometry, suggesting load-induced
      changes in bone material properties. This study shows that the cancellous and
      cortical anabolic responses to mechanical stimuli decline with age into adulthood
      and that cortical cross-sectional geometry alone does not necessarily predict
      whole-bone functional stiffness. 

PMID- 24577447
TI  - Cold acclimation alters the connective tissue content of the zebrafish (Danio
      rerio) heart.
AB  - Thermal acclimation can alter cardiac function and morphology in a number of fish
      species, but little is known about the regulation of these changes. The purpose
      of the present study was to determine how cold acclimation affects zebrafish
      (Danio rerio) cardiac morphology, collagen composition and connective tissue
      regulation. Heart volume, the thickness of the compact myocardium, collagen
      content and collagen fiber composition were compared between control (27 degrees
      C) and cold-acclimated (20 degrees C) zebrafish using serially sectioned hearts
      stained with Picrosirius Red. Collagen content and fiber composition of the
      pericardial membrane were also examined. Cold acclimation did not affect the
      volume of the contracted heart; however, there was a significant decrease in the
      thickness of the compact myocardium. There was also a decrease in the collagen
      content of the compact myocardium and in the amount of thick collagen fibers
      throughout the heart. Cold-acclimated zebrafish also increased expression of the
      gene transcript for matrix metalloproteinase 2, matrix metalloproteinase 9,
      tissue inhibitor of metalloproteinase 2 and collagen Type I alpha1. We propose
      that the reduction in the thickness of the compact myocardium as well as the
      change in collagen content may help to maintain the compliance of the ventricle
      as temperatures decrease. Together, these results clearly demonstrate that the
      zebrafish heart undergoes significant remodeling in response to cold acclimation.

PMID- 24577446
TI  - The olfactory neuron AWC promotes avoidance of normally palatable food following
      chronic dietary restriction.
AB  - Changes in metabolic state alter foraging behavior and food preference in
      animals. Here, I show that normally attractive food becomes repulsive to
      Caenorhabditis elegans if animals are chronically undernourished as a result of
      alimentary tract defects. This behavioral plasticity is achieved in two ways:
      increased food leaving and induction of aversive behavior towards food. A
      particularly strong food avoider is defective in the chitin synthase that makes
      the pharyngeal lining. Food avoidance induced by underfeeding is mediated by cGMP
      signaling in the olfactory neurons AWC and AWB, and the gustatory neurons ASJ and
      ASK. Food avoidance is enhanced by increased population density and is reduced if
      the animals are unable to correctly interpret their nutritional state as a result
      of defects in the AMP kinase or TOR/S6kinase pathways. The TGF-beta/DBL-1 pathway
      suppresses food avoidance and the cellular basis for this is distinct from its
      role in aversive olfactory learning of harmful food. This study suggests that
      nutritional state feedback via nutrient sensors, population size and olfactory
      neurons guides food preference in C. elegans. 

PMID- 24577448
TI  - Satellite cell activation and populations on single muscle-fiber cultures from
      adult zebrafish (Danio rerio).
AB  - Satellite cells (SCs), stem cells in skeletal muscle, are mitotically quiescent
      in adult mammals until activated for growth or regeneration. In mouse muscle, SCs
      are activated by nitric oxide (NO), hepatocyte growth factor (HGF) and the
      mechanically induced NO-HGF signaling cascade. Here, the SC population on fibers
      from the adult, ectothermic zebrafish and SC responsiveness to activating stimuli
      were assessed using the model system of isolated fibers cultured at 27 and 21
      degrees C. SCs were identified by immunostaining for the HGF receptor, c-met, and
      activation was determined using bromodeoxyuridine uptake in culture or in vivo.
      In dose-response studies, SC activation was increased by treatment with the NO
      donor drug isosorbide dinitrate (1 mmol l(-1)) or HGF (10 ng ml(-1)) to maximum
      activation at lower concentrations of both than in previous studies of mouse
      fibers. HGF-induced activation was blocked by anti-c-met antibody, and reduced by
      culture at 21 degrees C. The effect of cyclical stretch (3 h at 4 cycles per
      minute) increased activation and was blocked by nitric oxide synthase inhibition
      and reduced by culture at 21 degrees C. The number of c-met+ SCs per fiber
      increased rapidly (by 3 h) after stretching. The character of signaling in SC
      activation on zebrafish fibers, in particular temperature-dependent responses to
      HGF and stretch, gives new insights into the influence of ectothermy on
      regulation of muscle growth in teleosts and suggests the use of the single-fiber
      model system to explore the basis of fiber hyperplasia and the conservation of
      regulatory pathways between species. 

PMID- 24577450
TI  - Vocal production complexity correlates with neural instructions in the oyster
      toadfish (Opsanus tau).
AB  - Sound communication is fundamental to many social interactions and essential to
      courtship and agonistic behaviours in many vertebrates. The swimbladder and
      associated muscles in batrachoidid fishes (midshipman and toadfish) is a unique
      vertebrate sound production system, wherein fundamental frequencies are
      determined directly by the firing rate of a vocal-acoustic neural network that
      drives the contraction frequency of superfast swimbladder muscles. The oyster
      toadfish boatwhistle call starts with an irregular sound waveform that could be
      an emergent property of the peripheral nonlinear sound-producing system or
      reflect complex encoding in the central nervous system. Here, we demonstrate that
      the start of the boatwhistle is indicative of a chaotic strange attractor, and
      tested whether its origin lies in the peripheral sound-producing system or in the
      vocal motor network. We recorded sound and swimbladder muscle activity in awake,
      freely behaving toadfish during motor nerve stimulation, and recorded sound,
      motor nerve and muscle activity during spontaneous grunts. The results show that
      rhythmic motor volleys do not cause complex sound signals. However, arrhythmic
      recruitment of swimbladder muscle during spontaneous grunts correlates with
      complex sounds. This supports the hypothesis that the irregular start of the
      boatwhistle is encoded in the vocal pre-motor neural network, and not caused by
      peripheral interactions with the sound-producing system. We suggest that sound
      production system demands across vocal tetrapods have selected for muscles and
      motorneurons adapted for speed, which can execute complex neural instructions
      into equivalently complex vocalisations. 

PMID- 24577449
TI  - Gut microbiota dictates the metabolic response of Drosophila to diet.
AB  - Animal nutrition is profoundly influenced by the gut microbiota, but knowledge of
      the scope and core mechanisms of the underlying animal-microbiota interactions is
      fragmentary. To investigate the nutritional traits shaped by the gut microbiota
      of Drosophila, we determined the microbiota-dependent response of multiple
      metabolic and performance indices to systematically varied diet composition. Diet
      dependent differences between Drosophila bearing its unmanipulated microbiota
      (conventional flies) and experimentally deprived of its microbiota (axenic flies)
      revealed evidence for: microbial sparing of dietary B vitamins, especially
      riboflavin, on low-yeast diets; microbial promotion of protein nutrition,
      particularly in females; and microbiota-mediated suppression of
      lipid/carbohydrate storage, especially on high sugar diets. The microbiota also
      sets the relationship between energy storage and body mass, indicative of
      microbial modulation of the host signaling networks that coordinate metabolism
      with body size. This analysis identifies the multiple impacts of the microbiota
      on the metabolism of Drosophila, and demonstrates that the significance of these
      different interactions varies with diet composition and host sex. 

PMID- 24577451
TI  - Convergence in morphology and masticatory function between the pharyngeal jaws of
      grass carp, Ctenopharyngodon idella, and oral jaws of amniote herbivores.
AB  - The cellulose-rich walls that protect plant cells are difficult to digest, and
      therefore mechanical food processing is a key aspect of herbivory across
      vertebrates. Cell walls are typically broken down by translation of flattened
      teeth in the occlusal plane (i.e. grinding) as part of a complex, rhythmic
      chewing stroke. The grass carp, Ctenopharyngodon idella, is a voracious, invasive
      herbivorous fish that relies solely on its pharyngeal teeth, located in the back
      of the throat, for mechanical processing of plant material. Here, we describe the
      musculoskeletal anatomy of the pharyngeal jaws of grass carp and use XROMM to
      quantify chewing kinematics and muscle strain. The pharyngeal jaws are suspended
      in a sling of 11 muscles and maintain no bony articulation with any other
      skeletal elements in the head. The jaws bear long, serrated teeth that are worn
      during use into flattened tooth cusps. Our kinematic data show that this wear is
      the result of the teeth being elevated into occlusion against the basioccipital
      process and keratinous chewing pad, not tooth-on-tooth occlusion. Pharyngeal jaw
      elevation results from large strains in the jaw elevator muscle, the levator
      arcus branchialis V, to drive a pulley-like mechanism that rotates the jaws about
      a pivot point at the symphysis between the left and right pharyngeal jaws. These
      complex, rhythmic jaw rotations translate the teeth laterally across the chewing
      surface throughout the occlusion phase. The grass carp chewing system is
      strikingly similar in gross morphology and masticatory function to herbivorous
      chewing strategies in other vertebrates. 

PMID- 24577452
TI  - Is gastrointestinal plasticity in king quail (Coturnix chinensis) elicited by
      diet-fibre or diet-energy dilution?
AB  - Phenotypic plasticity of organ size allows some animals to manage fluctuations of
      resource quality or availability. Here, we examined the phenotypic plasticity of
      the gastrointestinal tract of king quail (Coturnix chinensis) in a diet-fibre
      manipulation study. Quail were offered either a control low-fibre (high-quality)
      food (8.5% neutral-detergent fibre; NDF), or one of two experimental diets of
      higher fibre contents of 16% NDF (i.e. low-quality food). To examine whether
      phenotypic plasticity of organ size was associated with the fibre content per se,
      or as a consequence of diluting the diet energy contents by adding fibre, one of
      the high-fibre feeds was 'balanced' with additional energy to match that of the
      low-fibre control diet. Total empty dry mass of the gastrointestinal tract was
      significantly heavier among birds offered the unbalanced high-fibre diet as
      compared with those offered the control diet, with birds offered the fibrous but
      energy-balanced diet having guts of intermediate size. The heavier entire-gut
      mass (dry) of quail offered the unbalanced high-fibre diet was associated mainly
      with these birds having significantly heavier gizzards. Notably, the larger
      gizzard in the birds offered the unbalanced high-fibre diet was associated with
      marked increases in their metabolisability (digestion) of diet fibre. Our
      findings suggest that the available energy in the diet may be more important for
      eliciting phenotypic changes in the gut of these herbivorous birds rather than
      simple physical effects of diet fibre on feed intakes or on muscular compensation
      to fibrous ingesta. 

PMID- 24577453
TI  - Glycolysis plays an important role in energy transfer from the base to the distal
      end of the flagellum in mouse sperm.
AB  - Many studies have been conducted to elucidate the relationship between energy
      metabolic pathways (glycolysis and respiration) and flagellar motility in
      mammalian sperm, but the contribution of glycolysis to sperm motility has not yet
      been fully elucidated. In the present study, we performed detailed analysis of
      mouse sperm flagellar motility for further understanding of the contribution of
      glycolysis to mammalian sperm motility. Mouse sperm maintained vigorous motility
      in the presence of substrates either for glycolysis or for respiration. By
      contrast, inhibition of glycolysis by alpha-chlorohydrine caused a significant
      decrease in the bend angle of the flagellar bending wave, sliding velocity of
      outer doublet microtubules and ATP content even in the presence of respiratory
      substrates (pyruvate or beta-hydroxybutyrate). The decrease of flagellar bend
      angle and sliding velocity are prominent in the distal part of the flagellum,
      indicating that glycolysis inhibition caused the decrease in ATP concentration
      threrein. These results suggest that glycolysis potentially acts as a spatial ATP
      buffering system, transferring energy (ATP) synthesized by respiration at the
      mitochondria located in the basal part of the flagellum to the distal part. In
      order to validate that glycolytic enzymes can transfer high energy phosphoryls,
      we calculated intraflagellar concentration profiles of adenine nucleotides along
      the flagellum by computer simulation analysis. The result demonstrated the
      involvement of glycolysis for maintaining the ATP concentration at the tip of the
      flagellum. It is likely that glycolysis plays a key role in energy homeostasis in
      mouse sperm not only through ATP production but also through energy transfer. 

PMID- 24577454
TI  - The glycemic index of pigmented potatoes is related to their polyphenol content.
AB  - Polyphenol extracts from coloured fruits and vegetables inhibit alpha-glucosidase
      in vitro, however it is not known whether this translates into an attenuation of
      blood glucose response in vivo. We examined this relationship in a GI study by
      feeding coloured potatoes to 9 healthy volunteers. We also examined the in vitro
      inhibitory activity of potato anthocyanin extracts on rat intestinal alpha
      glucosidase. Potatoes (Purple Majesty; Red-Y38; Yukon Gold and Snowden) were fed
      with skin after cooking in a convection oven, using a random block design and 50
      g available carbohydrate. Glucose was used as the standard and venous blood
      collected at 0, 15, 30, 45, 60, 90, 120 min. Areas under the curve (AUC) for
      glucose and insulin were calculated, and GI and Insulin Index derived. Neither
      AUC for blood glucose response nor insulin was significantly different among the
      various potatoes studied. Although the mean GI (+/-SE) values for the potato
      types varied (purple = 77.0 +/- 9.0; red = 78.0 +/- 14.0; yellow = 81.0 +/- 16.0;
      and white = 93.0 +/- 17.0), these differences were not significantly different.
      The mean (+/-SE) polyphenol content (mg GAE/100 g DW) was 234 +/- 28; 190 +/- 15;
      108 +/- 39; 82 +/- 1 for purple, red, yellow and white potatoes, respectively.
      There was a significant inverse correlation between polyphenol content and GI of
      the potatoes (r = -0.825; p < 0.05; n = 4). In vitro, polyphenol extracts of red
      and purple potatoes inhibited alpha-glucosidase by 37.4 +/- 2.2% and 28.7 +/-
      3.2%, respectively. The GI of coloured potatoes is significantly related to their
      polyphenol content, possibly mediated through an inhibitory effect of
      anthocyanins on intestinal alpha-glucosidase. 

PMID- 24577456
TI  - Genome-wide serum microRNA expression profiling identifies serum biomarkers for
      Alzheimer's disease.
AB  - Recent findings that human serum contains stably expressed microRNAs (miRNAs)
      have revealed a great potential of serum miRNA signature as disease fingerprints
      to diagnosis. Here we used genome-wide serum miRNA expression analysis to
      investigate the value of serum miRNAs as biomarkers for the diagnosis of
      Alzheimer's disease (AD). Illumina HiSeq 2000 sequencing followed by individual
      quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) assays was
      used to test the difference in levels of serum miRNAs between 50 AD patients and
      50 controls in the screening stages. The detected serum miRNAs then were
      validated by qRT-PCR in 158 patients and 155 controls. MiR-98-5p, miR-885-5p, miR
      483-3p, miR-342-3p, miR-191-5p, and miR-let-7d-5p displayed significantly
      different expression levels in AD patients compared with controls. Among the 6
      miRNAs, miR-342-3p has the best sensitivity (81.5%) and specificity (70.1%) and
      was correlated to Mini-Mental State Examination score. This study identified six
      serum miRNAs that distinguish AD patients from healthy controls with high
      sensitivity and specificity. Serum miRNA panel (or miR-342-3p alone) may serve as
      a novel, noninvasive biomarker for AD. 

PMID- 24577455
TI  - The Italian Alzheimer's Disease Neuroimaging Initiative (I-ADNI): validation of
      structural MR imaging.
AB  - BACKGROUND: The North American Alzheimer's Disease Neuroimaging Initiative (NA
      ADNI) was the first program to develop standardized procedures for Alzheimer's
      disease (AD) imaging biomarker collection. OBJECTIVE: We describe the validation
      of acquisition and processing of structural magnetic resonance imaging (MRI) in
      different Italian academic AD clinics following NA-ADNI procedures. METHODS: 373
      patients with subjective memory impairment (n = 12), mild cognitive impairment (n
      = 92), Alzheimer's dementia (n = 253), and frontotemporal dementia (n = 16) were
      enrolled in 9 Italian centers. 22 cognitively healthy elderly controls were also
      included. MRI site qualification and MP-RAGE quality assessment was applied
      following the NA-ADNI procedures. Indices of validity were: (i) NA-ADNI phantom's
      signal-to-noise and contrast-to-noise ratio, (ii) proportion of images passing
      quality control, (iii) comparability of automated intracranial volume (ICV)
      estimates across scanners, and (iv) known-group validity of manual hippocampal
      volumetry. RESULTS: Results on Phantom and Volunteers scans showed that I-ADNI
      acquisition parameters were comparable with those one of the ranked-A ADNI scans.
      Eighty-seven percent of I-ADNI MPRAGE images were ranked of high quality in
      comparison of 69% of NA-ADNI. ICV showed homogeneous variances across scanners
      except for Siemens scanners at 3.0 Tesla (p = 0.039). A significant difference in
      hippocampal volume was found between AD and controls on 1.5 Tesla scans (p <
      0.001), confirming known group validity test. CONCLUSION: This study has provided
      standardization of MRI acquisition and imaging marker collection across different
      Italian clinical units and equipment. This is a mandatory step to the
      implementation of imaging biomarkers in clinical routine for early and
      differential diagnosis.

PMID- 24577458
TI  - Do cholinesterase inhibitors act primarily on attention deficit? A naturalistic
      study in Alzheimer's disease patients.
AB  - Attention is the first non-memory domain affected in Alzheimer's disease (AD),
      before deficits in language and visuo-spatial function, and it is claimed that
      attention deficits are responsible for the difficulties with daily living in
      early demented patients. The aim of this longitudinal study in a group of 121
      Caucasian, community-dwelling, mild-to-moderate AD patients (Mini-Mental State
      Examination (MMSE) score >17) was to detect which cognitive domains were most
      affected by the disease and whether one year treatment with cholinesterase
      inhibitors was more effective in preserving attention than memory. All subjects
      were evaluated by a neuropsychological battery including global measurements
      (MMSE, Information-Memory-Concentration Test) and tasks exploring verbal long
      term memory, language, attention, and executive functions. The comparison between
      two evaluations, made 12 months apart, shows statistically significant
      differences, indicating deterioration compared to baseline, in the following
      tests: MMSE (with no gender differences), Composite Memory Score, Short Story
      Delayed Recall, Trail-Making Test A, Semantic Fluency Test, and Token Test.
      Conversely, there were no differences in the two evaluations of the Digit Span,
      Corsi Tapping Test, Short Story Immediate Recall, and Phonemic Fluency Tests. It
      appears that the treatment specifically attenuated the decline in tests assessing
      attention and executive functions. A stabilization of the ability to pay
      attention, with the ensuing positive effects on executive functions, recent
      memory, and information acquisition which depend on attention, appears to be the
      main neuropsychological mechanism through which the activation of the cholinergic
      system, resulting from cholinesterase inhibition, exerts its effect on cognition.

PMID- 24577459
TI  - Post-stroke cognitive impairment: high prevalence and determining factors in a
      cohort of mild stroke.
AB  - BACKGROUND: Because of the aging population and a rise in the number of stroke
      survivors, the prevalence of post-stroke cognitive impairment (PSCI) is
      increasing. OBJECTIVE: To identify the factors associated with 3-month PSCI.
      METHODS: All consecutive stroke patients without pre-stroke dementia, mild
      cognitive disorders, or severe aphasia hospitalized in the Neurology Department
      of Dijon, University Hospital, France (November 2010 - February 2012) were
      included in this prospective cohort study. Demographics, vascular risk factors,
      and stroke data were collected. A first cognitive evaluation was performed during
      the hospitalization using the Mini-Mental State Exam (MMSE) and the Montreal
      Cognitive Assessment (MOCA). Patients assessable at 3 months were categorized as
      cognitively impaired if the MMSE score was <=26/30 and MOCA <26/30 or if the
      neuropsychological battery confirmed PSCI when the MMSE and MOCA were discordant.
      Multivariable logistic models were used to determine factors associated with 3
      month PSCI. RESULTS: Among the 280 patients included, 220 were assessable at 3
      months. The overall frequency of 3-month PSCI was 47.3%, whereas that of dementia
      was 7.7%. In multivariable analyses, 3-month PSCI was associated with age, low
      education level, a history of diabetes mellitus, acute confusion, silent
      infarcts, and functional handicap at discharge. MMSE and MOCA scores during
      hospitalization were associated with 3-month PSCI (OR = 0.63; 95% CI: 0.54-0.74;
      p < 0.0001 and OR = 0.67; 95% CI: 0.59-0.76; p < 0.0001, respectively).
      CONCLUSION: Our study underlines the high frequency of PSCI in a cohort of mild
      stroke. The early cognitive diagnosis of stroke patients could be useful by
      helping physicians to identify those at a high risk of developing PSCI.

PMID- 24577457
TI  - White matter hyperintensities are associated with amyloid burden in APOE4 non
      carriers.
AB  - Previous preclinical studies have suggested a close relationship between
      cerebrovascular disease (CVD) and Alzheimer's disease. However, a direct
      correlation between CVD and amyloid burden has not yet been shown in humans. If
      there is a relationship between CVD and amyloid burden, it is possible that the
      apolipoprotein E4 (APOE4) genotype may have an effect on this relationship
      because APOE4 is a risk factor for the development of AD. We therefore evaluated
      the effects of APOE4 on the relationship between white matter hyperintensities
      (WMH), a marker of CVD, and amyloid burden, measured by 11C-Pittsburgh compound B
      (PiB) PET. We recruited 53 patients with subcortical vascular cognitive
      impairments, who had both WMH on MRI and amyloid deposition assessed by PiB PET.
      Twenty-two of these patients were APOE4 carriers (41.5%). In the APOE4 non
      carriers, a significant positive correlation was shown between the volume of WMH
      and PiB retention (beta = 7.0 * 10-3, p = 0.034) while no significant correlation
      was found in APOE4 carriers (beta = -9.0 * 10-3, p = 0.085). Statistical
      parametric mapping analyses in APOE4 non-carriers showed that WMH were associated
      with PiB retention in the bilateral medial occipitotemporal gyrus, cuneus, and
      superior cerebellum. Our results suggested that WMH are correlated with amyloid
      burden especially in the posterior brain regions in APOE4 non-carriers. However,
      this correlation was not observed in APOE4 carriers, perhaps because in these
      subjects the influence of APOE4 overrides the effect of CVD. 

PMID- 24577460
TI  - Actigraphic motor activity in mild cognitive impairment patients carrying out
      short functional activity tasks: comparison between mild cognitive impairment
      with and without depressive symptoms.
AB  - BACKGROUND: Individuals with mild cognitive impairment (MCI) may exhibit changes
      in motor activity in conducting their activities of daily living. Depression, one
      of the most frequent neuropsychiatric symptoms, might affect motor activity in
      MCI. OBJECTIVE: To assess motor activity in MCI subjects carrying out short
      functional activity tasks using ambulatory actigraphy. Secondly, we sought to
      investigate the influence of depressive symptoms on motor activity. METHODS: 20
      MCI and 14 healthy subjects carried out a 30-minute standardized scenario while
      wearing a chest actigraph. The protocol consisted of directed activities
      (execution of motor tasks), semi-directed activities (execution of Instrumental
      Activities of Daily Living, IADL), and undirected 'free' activities. Several
      common assessment scales (GDS, MADRS, and NPI) were used to diagnose depression.
      RESULTS: MCI subjects had significantly reduced mean motor activity while
      carrying out directed and semi-directed activities, compared to healthy control
      subjects. No difference was found in motor activity between MCI subjects with or
      without depression. CONCLUSION: Actigraphic measurement of motor activity during
      the evaluation of IADLs and motor tasks is a potential objective tool in
      detecting early changes in MCI. Depressive symptoms seem not to be associated
      with motor activity in MCI subjects.

PMID- 24577461
TI  - The impact of APOE status on relationship of biomarkers of vascular risk and
      systemic inflammation to neuropsychiatric symptoms in Alzheimer's disease.
AB  - Research on the link between APOEepsilon4 and neuropsychiatric symptoms (NPS) in
      Alzheimer's disease (AD) has been inconsistent. Previous work has shown a
      relationship between serum biomarkers of vascular risk and inflammation and NPS
      in AD. The current study investigated the impact of APOEepsilon4 status on the
      relationship between biomarkers of cardiovascular risk, systemic inflammation,
      and NPS. The sample was drawn from the TARCC Longitudinal Research Cohort; the
      final sample of 190 consisted of 124 females and 66 males meeting the diagnostic
      criteria for mild to moderate AD. 115 individuals were APOEepsilon4 carriers and
      75 were non-carriers. Serum-based clinical biomarkers of vascular risk and
      biomarkers of inflammation related to AD were analyzed. NPS data was gathered
      from caretakers/family members using the Neuropsychiatric Inventory. The
      significant biomarkers differed for carriers and non-carriers with IL15 being a
      negative biomarker of total NPS accounting for 12% of the variance for carriers
      and IL18 and TNFalpha negative predictors for non-carriers (18% of variance).
      Patterns related to specific symptoms were similar. Stratification by gender
      revealed significant biomarkers of total NPS for female carriers were negative
      IL15 and IL1ra (18% of variance) and for female non-carriers were negative IL18
      and positive homocysteine. Total cholesterol was a positive biomarker of total
      NPS for both male carriers (36% of variance) and non-carriers (negative TNFalpha
      and total cholesterol, 32% of variance). These findings suggest that
      dysregulation of inflammatory activity is related to NPS, that cholesterol is a
      significant factor in the occurrence of NPS, and that gender and APOE status need
      to be considered. 

PMID- 24577462
TI  - The temporospatial evolution of neuritic plaque-related and independent
      tauopathies: implications for dementia staging.
AB  - Neuritic plaque (NP) formation can be dated in vivo. This analysis attempts to
      "date" the progression of neurofibrillary tangles (NFT) using the spatial
      distribution of NP as a reference. Autopsy data from 471 participants in the
      Honolulu-Asia Aging Study (HAAS) were combined into latent factor measures of NFT
      and NP counts. The variance in "early" and "late" NP pathology was used to
      estimate the spatial distribution of "early" and "late" NFT formation. A third
      latent factor representing "non-NP-related NFT" was also constructed. "Early" NP
      and "late" NP correlated significantly with objectively early and later cognitive
      performance, respectively. In contrast to our expectations, neocortical NFT
      correlated best with "early" NP pathology, while NFT in allocortical structures
      correlated best with "late" NP pathology. Therefore, the NP-related fraction of
      NFT appears to be co-localized spatially with NP. However, since the latter
      evolve corticofugally in time, this suggests that NP-related NFT do so as well.
      Corticotropic NFT formation must therefore be either unrelated to NP formation, a
      temporally distinct process, or both. 

PMID- 24577463
TI  - Long-term metformin usage and cognitive function among older adults with
      diabetes.
AB  - Evidence strongly supports the important role of insulin resistance in cognitive
      decline and dementia and suggests that insulin sensitizers may protect against
      cognitive decline in diabetic and pre-diabetic individuals. Inconclusive results
      have been reported in clinical trials of rosiglitazone, an insulin sensitizer
      that also increases cardiovascular mortality risks. No study has yet reported a
      protective cognitive effect of metformin, an insulin-sensitizing biguanide widely
      used in diabetic patients. We studied 365 older persons aged 55 and over in the
      population-based Singapore Longitudinal Aging Study with diabetes who were
      followed up over 4 years. The odds ratios (OR) of association of metformin use (n
      = 204) versus non-use (n = 161) with cognitive impairment (Mini-Mental State Exam
      <= 23), and by duration: up to 6 years (n = 114) and more than 6 years (n = 90)
      were evaluated in cross-sectional and longitudinal multivariate analyses.
      Controlling for age, education, diabetes duration, fasting blood glucose,
      vascular and non-vascular risk factors, metformin use showed a significant
      inverse association with cognitive impairment in longitudinal analysis (OR =
      0.49, 95% CI 0.25-0.95). Metformin use showed significant linear trends of
      association across duration of use in cross-sectional and longitudinal analyses
      (p = 0.018 and p = 0.002, respectively), with use for more than 6 years
      significantly associated with lowest risk of cognitive impairment in both cross
      sectional analysis (OR = 0.30, 95% CI 0.11-0.80) and in longitudinal analysis (OR
      = 0.27, 95% CI 0.12-0.60). No significant interactive effects of metformin use
      with APOE-epsilon4, depression, or fasting glucose level were observed. Among
      individuals with diabetes, long-term treatment with metformin may reduce the risk
      of cognitive decline. Further studies should establish the role of hyperglycemia
      and insulin resistance, and the protective role of metformin in the risk of
      cognitive decline and dementia. 

PMID- 24577465
TI  - Brain-penetrating angiotensin-converting enzyme inhibitors and cognitive change
      in patients with dementia due to Alzheimer's disease.
AB  - Controversy over benefits of angiotensin-converting enzyme inhibitors (ACEIs) for
      treatment of dementia due to Alzheimer's disease (AD) led to this alternative
      investigational approach by the employment of pharmacogenetic methods,
      correlating the cognitive change of patients with late-onset AD with the presence
      of common ACE gene promoter polymorphisms, and stratifying the sample in groups
      of patients who responded or not to the brain-penetrating ACEIs Captopril or
      Perindopril. A trend was found for treatment with brain-penetrating ACEIs to slow
      cognitive decline in AD patients with the haplotype rs1800764 (CC): rs4291 (TT)
      (p = 0.024), and also non-significantly for independent carriers of rs1800764 or
      rs4291. 

PMID- 24577464
TI  - Central and peripheral administration of antisense oligonucleotide targeting
      amyloid-beta protein precursor improves learning and memory and reduces
      neuroinflammatory cytokines in Tg2576 (AbetaPPswe) mice.
AB  - Alzheimer's disease (AD) is a progressive neurodegenerative disease. Currently,
      there are no therapies to stop or reverse the symptoms of AD. We have developed
      an antisense oligonucleotide (OL-1) against the amyloid-beta protein precursor
      (AbetaPP) that can decrease AbetaPP expression and amyloid-beta protein (Abeta)
      production. This antisense rapidly crosses the blood-brain barrier, reverses
      learning and memory impairments, reduces oxidative stress, and restores brain-to
      blood efflux of Abeta in SAMP8 mice. Here, we examined the effects of this
      AbetaPP antisense in the Tg2576 mouse model of AD. We administered the OL-1
      antisense into the lateral ventricle 3 times at 2week intervals. Seventy-two
      hours after the third injection, we tested learning and memory in T-maze foot
      shock avoidance. In the second study, we injected the mice with OL-1 antisense 3
      times at 2-week intervals via the tail vein. Seventy-two hours later, we tested
      learning and memory T-maze, novel object recognition, and elevated plus maze. At
      the end of behavioral testing, brain tissue was collected. OL-1 antisense
      administered centrally improved acquisition and retention of T-maze foot shock
      avoidance. OL-1 antisense administered via tail vein improved learning and memory
      in both T-maze foot shock avoidance and novel object-place recognition. In the
      elevated plus maze, the mice which received OL-1 antisense spent less time in the
      open arms and had fewer entries into the open arms indicating reduced
      disinhibitation. Biochemical analyses reveal significant reduction of AbetaPP
      signal and a reduction of measures of neuroinflammation. The current findings
      support the therapeutic potential of OL-1 AbetaPP antisense. 

PMID- 24577466
TI  - Usefulness of biomarkers in the diagnosis and prognosis of early-onset cognitive
      impairment.
AB  - Early-onset cognitive impairment diagnosis is often challenging due to the
      overlapping symptoms between the different degenerative and non-degenerative
      conditions. We aimed to evaluate the usefulness of cerebrospinal fluid (CSF)
      biomarkers in early-onset cognitive impairment differential diagnosis, to assess
      their contribution to the diagnosis of Alzheimer's disease (AD) based on the new
      National Institute of Aging-Alzheimer's Association (NIA-AA) workgroup's
      recommendations and their capacity to predict subsequent decline in early-onset
      mild cognitive impairment (MCI). 37 controls and 120 patients (clinical onset <65
      years) with diagnosis based on criteria available in 2009 (51 MCI, 42 AD, 10
      frontotemporal dementia (FTD), 3 posterior cortical atrophy, and 14 primary
      progressive aphasia (PPA)) were included. In addition, all subjects were also
      reclassified according to the revised criteria for MCI, AD, FTD, and PPA,
      excluding CSF data. We assessed the impact of adding the CSF data to the subject
      categorization according to the NIA-AA criteria. After inclusion of CSF results,
      90% of amnestic and 82% of the non-amnestic AD presentation could be categorized
      as "high probability", while 3% of AD patients fit into the category "dementia
      probably not due to AD". All the 24 MCI patients who progressed to AD dementia
      and only 1/27 stable MCI presented pathological CSF at baseline. Only 4% of the
      FTD clinical diagnosis had pathological CSF levels. CSF biomarkers provide high
      diagnostic accuracy in a clinical context in differentiating AD, frontotemporal
      lobar degeneration, and controls in presenile subjects and can be used equally in
      amnestic and non-amnestic AD. Abnormal CSF-AD biomarker levels predict subsequent
      progression to AD dementia in subjects with early-onset MCI. 

PMID- 24577467
TI  - Choroidal thinning as a new finding in Alzheimer's disease: evidence from
      enhanced depth imaging spectral domain optical coherence tomography.
AB  - BACKGROUND: The involvement of retina and its vasculature has been recently
      described in Alzheimer's disease (AD). However, none of the previous works have
      yet investigated the choroid in vivo. OBJECTIVE: Spectral domain optical
      coherence tomography (SD-OCT) and enhanced depth imaging (EDI) technique is non
      invasively used to assess choroidal thickness in patients with AD and to
      determine whether the peripapillary retinal nerve fiber layer (RNFL) and central
      retinal thickness are reduced compared to normal subjects. METHODS: Forty-two
      eyes of 21 patients (mean age, 73.1 +/- 6.9 years) with a diagnosis of mild to
      moderate AD and 42 eyes of 21 age-matched control subjects (mean age, 70.3 +/-
      7.3 years) were included in this prospective, cross-sectional study. All the
      subjects underwent neuropsychological (MMSE, ADAS-Cog, and CDR) and
      ophthalmological evaluation. The SD-OCT images of the choroid were obtained by
      EDI modality. Choroidal thickness was assessed by manual measurement. The
      following parameters, measured automatically by the OCT software, were also
      analyzed for each eye: 1-mm central subfield (CSF) retinal thickness,
      peripapillary RNFL thickness. RESULTS: Choroidal thickness was significantly
      thinner in AD than in control eyes (p < 0.05). No difference in CSF retinal
      thickness was found between groups (p > 0.05). Mean peripapillary RNFL thickness
      in all four quadrants was similar between groups (p > 0.05). OCT measurements
      were not correlated with any of the tested psychometric parameters (p > 0.05).
      CONCLUSION: Compared with healthy subjects, patients with AD showed a significant
      reduction in choroidal thickness. Choroidal thinning may represent an adjunctive
      biomarker for the diagnosis and follow-up of this disease.

PMID- 24577468
TI  - Longitudinal assessment of a transgenic animal model of tauopathy by FDG-PET
      imaging.
AB  - Abnormal levels and hyperphosphorylation of tau protein have been proposed as the
      underlying cause of a group of neurodegenerative disorders collectively known as
      'tauopathies'. The detrimental consequence is the loss of affinity between this
      protein and the microtubules, increased production of fibrillary aggregates, and
      the accumulation of insoluble intracellular neurofibrillary tangles. A similar
      phenotype can be observed in various preclinical models, which have been
      generated to study the role of tau protein in neurodegenerative disorders. In
      this study, we have analyzed the brain metabolic activity in an animal model of
      tauopathy (tauVLW transgenic mice), which has been previously reported to mimic
      some of the phenotypic features of these disorders. By using a non-invasive
      technique, positron emission tomography (PET), a longitudinal non-clinical follow
      up study was carried out during most of the lifespan of these transgenic mice,
      from the youth to the senescence stages. The results obtained point out to an
      aging-dependent decrease in 18F-fluoro-deoxyglucose (FDG) uptake in the cerebral
      areas analyzed, which was already significant at the adult age, i.e., 11 months,
      and became much more prominent in the oldest animals (19 months old). This
      observation correlates well with the histopathological observation of
      neurodegeneration in brain areas where there is overexpression of tau protein. 

PMID- 24577469
TI  - Who needs cerebrospinal biomarkers? A national survey in clinical practice.
AB  - Cerebrospinal fluid (CSF) biomarkers for Alzheimer's disease (AD) are well
      validated in clinical research but less in clinical practice. Using a
      questionnaire, we evaluated the reasons for prescriptions and clinician's
      expectations concerning CSF biomarkers. The results show that CSF AD biomarkers
      are mainly required in case of atypical dementia and diagnosis uncertainty that
      are different from indications in clinical research. In the future, clinicians
      wish to get new biomarkers that could improve differential diagnosis and could
      have a good pronostic value. Further studies in routine practice are necessary to
      precise the role of these biomarkers in the management of patients. 

PMID- 24577470
TI  - Argyrophilic grain pathology as a natural model of tau propagation.
AB  - Argyrophilic grain disease (AGD) is a sporadic 4 R tauopathy that usually
      presents in combination with other sporadic tauopathies or with Alzheimer's
      disease (AD) pathology, and may contribute to dementia in older age patients. In
      previous studies, a detailed analysis of AGD pathology in the medial temporal
      lobe has been hampered by the common presence of concurrent AD changes. With the
      objective to assess the potentiality of AGD in research on tau propagation, here
      we present a study of a series of AGD postmortem cases (n = 53). The total series
      was divided in a subgroup of cases with Braak-stage <= II (n = 23) and a subgroup
      with Braak-stage>II or indeterminate (n = 30) in order to minimize interference
      with AD pathology. A detailed neuropathological evaluation of the medial temporal
      lobe was performed at three coronal levels with Gallyas stain, and immunostains
      with p62, AT8, and AT100 antibodies. Western blot analysis of the entorhinal and
      hippocampal cortex was performed in 8 cases with a panel of anti-tau antibodies.
      Cases were genotyped for APOE polymorphism and for H1/H2 alleles of the MAPT
      gene. All cases, and particularly lower Braak-stage cases, displayed a highly
      homogeneous pattern of involvement by argyrophilic grains and pretangles between
      connected regions (primarily basolateral nuclei of the amygdala,
      entorhinal/transentorhinal cortex, and hippocampal cortex). Staging of cases
      reveals progression of pathology along well-established neuroanatomical pathways.
      Western blot studies yielded a specific pattern of isoforms with a characteristic
      predominant band at 64 kDa. Genetic analysis showed a strong association with the
      H1 allele of the MAPT gene. AGD may thus be an optimal natural disease model for
      testing hypotheses related to tau propagation in human tissue. 

PMID- 24577471
TI  - Acute caffeine administration effect on brain activation patterns in mild
      cognitive impairment.
AB  - Previous studies showed that acute caffeine administration enhances task-related
      brain activation in elderly individuals with preserved cognition. To explore the
      effects of this widely used agent on cognition and brain activation in early
      phases of cognitive decline, we performed a double-blinded, placebo-controlled
      functional magnetic resonance imaging (fMRI) study during an n-back working
      memory task in 17 individuals with mild cognitive impairment (MCI) compared to 17
      age-matched healthy controls (HC). All individuals were regular caffeine
      consumers with an overnight abstinence and given 200 mg caffeine versus placebo
      tablets 30 minutes before testing. Analyses included assessment of task-related
      activation (general linear model), functional connectivity (tensorial-independent
      component analysis, TICA), baseline perfusion (arterial spin labeling, ASL), grey
      matter density (voxel-based morphometry, VBM), and white matter microstructure
      (tract-based spatial statistics, TBSS). Acute caffeine administration induced a
      focal activation of the prefrontal areas in HC with a more diffuse and
      posteromedial activation pattern in MCI individuals. In MCI, TICA documented a
      significant caffeine-related enhancement in the prefrontal cortex, supplementary
      motor area, ventral premotor and parietal cortex as well as the basal ganglia and
      cerebellum. The absence of significant group differences in baseline ASL
      perfusion patterns supports a neuronal rather than a purely vascular origin of
      these differences. The VBM and TBSS analyses excluded potentially confounding
      differences in grey matter density and white matter microstructure between MCI
      and HC. The present findings suggest a posterior displacement of working memory
      related brain activation patterns after caffeine administration in MCI that may
      represent a compensatory mechanism to counterbalance a frontal lobe dysfunction. 

PMID- 24577472
TI  - Increased susceptibility to amyloid-beta-induced neurotoxicity in mice lacking
      the low-density lipoprotein receptor.
AB  - Familial hypercholesterolemia is caused by inherited genetic abnormalities that
      directly or indirectly affect the function of the low-density lipoprotein (LDL)
      receptor. This condition is characterized by defective catabolism of LDL which
      results in increased plasma cholesterol concentrations and premature coronary
      artery disease. Nevertheless, there is increasing preclinical and clinical
      evidence indicating that familial hypercholesterolemia subjects show a
      particularly high incidence of mild cognitive impairment. Moreover, the LDL
      receptor (LDLr) has been implicated as the main central nervous system
      apolipoprotein E receptor that regulates amyloid deposition in distinct mouse
      models of beta-amyloidosis. In this regard, herein we hypothesized that the lack
      of LDLr would enhance the susceptibility to amyloid-beta-(Abeta)-induced
      neurotoxicity in mice. Using the acute intracerebroventricular injection of
      aggregated Abeta(1-40) peptide (400 pmol/mouse), a useful approach for the
      investigation of molecular mechanisms involved in Abeta toxicity, we observed
      oxidative stress, neuroinflammation, and neuronal membrane damage within the
      hippocampus of C57BL/6 wild-type mice, which were associated with spatial
      reference memory and working memory impairments. In addition, our data show that
      LDLr knockout (LDLr(-/-)) mice, regardless of Abeta treatment, displayed memory
      deficits and increased blood-brain barrier permeability. Nonetheless, LDLr(-/-)
      mice treated with Abeta(1-40) peptide presented increased acetylcholinesterase
      activity, astrogliosis, oxidative imbalance, and cell permeability within the
      hippocampus in comparison with Abeta(1-40)-treated C57BL/6 wild-type mice.
      Overall, the present study shows that the lack of LDLr increases the
      susceptibility to Abeta-induced neurotoxicity in mice providing new evidence
      about the crosslink between familial hypercholesterolemia and cognitive
      impairment.

PMID- 24577473
TI  - Plasma concentrations of the amyloid-beta peptides in young volunteers: the
      influence of the APOE genotype.
AB  - Changes in the concentrations of amyloid-beta (Abeta) in the body fluids are the
      earliest alterations observed in Alzheimer's disease (AD), however, there is a
      lack of data about how early these alterations occur, before the onset of the
      clinical symptoms. APOE genotype is the most recognized genetic risk/protective
      factor of AD, meaning that a group of non-demented persons carrying epsilon4
      allele is enriched in the subjects who will develop AD, compared to the group of
      non-carriers. Therefore, we studied the plasma concentrations of Abeta peptides
      (Abeta1-42, Abeta1-40, Abetax-42, and Abetax-40), and the APOE genotype in 173
      young volunteers (average age, 28 +/- 7.6 years) without memory deficits, in
      order to see whether the non-demented group of subjects at risk already
      characterize with Abeta changes three-to-four decades before the age at which
      dementia usually occurs. We did not find statistically significant differences
      among the groups of epsilon4 carriers, epsilon3 homozygotes, and epsilon2
      carriers. We conclude that the APOE genotype does not influence the metabolism of
      the Abeta peptides in young persons without memory deficits. 

PMID- 24577474
TI  - Chronic aluminum intake causes Alzheimer's disease: applying Sir Austin Bradford
      Hill's causality criteria.
AB  - Industrialized societies produce many convenience foods with aluminum additives
      that enhance various food properties and use alum (aluminum sulfate or aluminum
      potassium sulfate) in water treatment to enable delivery of large volumes of
      drinking water to millions of urban consumers. The present causality analysis
      evaluates the extent to which the routine, life-long intake, and metabolism of
      aluminum compounds can account for Alzheimer's disease (AD), using Austin
      Bradford Hill's nine epidemiological and experimental causality criteria,
      including strength of the relationship, consistency, specificity, temporality,
      dose-dependent response, biological rationale, coherence with existing knowledge,
      experimental evidence, and analogy. Mechanisms that underlie the risk of low
      concentrations of aluminum relate to (1) aluminum's absorption rates, allowing
      the impression that aluminum is safe to ingest and as an additive in food and
      drinking water treatment, (2) aluminum's slow progressive uptake into the brain
      over a long prodromal phase, and (3) aluminum's similarity to iron, in terms of
      ionic size, allows aluminum to use iron-evolved mechanisms to enter the highly
      active, iron-dependent cells responsible for memory processing. Aluminum
      particularly accumulates in these iron-dependent cells to toxic levels,
      dysregulating iron homeostasis and causing microtubule depletion, eventually
      producing changes that result in disconnection of neuronal afferents and
      efferents, loss of function and regional atrophy consistent with MRI findings in
      AD brains. AD is a human form of chronic aluminum neurotoxicity. The causality
      analysis demonstrates that chronic aluminum intake causes AD. 

PMID- 24577475
TI  - Metabolic syndrome and longitudinal changes in cognitive function: a systematic
      review and meta-analysis.
AB  - BACKGROUND: Metabolic syndrome (MetS) is associated with an increased risk of
      coronary heart diseases and stroke. Results on the association of MetS with
      dementia and cognitive decline have been inconsistent. OBJECTIVE: The aim of this
      study was to examine the association between MetS and longitudinal changes in
      cognitive function. METHODS: Medline, EMBASE, and Scopus databases were searched
      from inception to June 2013. Longitudinal cohort studies that reported on the
      association between MetS and change in cognitive function (over two or more time
      points), were included. RESULTS: Random-effects models were used to assess the
      pooled effect sizes of longitudinal changes in cognitive function associated with
      MetS. Thirteen studies were included. The total sample size was 19,522 subjects.
      Follow up duration ranged from 1 to 16 years. In the total sample, a small
      association of MetS with cognitive decline was observed (SDM 0.06, 95%CI: -0.001,
      0.12; p = 0.05). When age-stratified, a marginal significant association between
      MetS and cognitive decline was observed in the younger old group (<=70 years; SDM
      = 0.09, 95%CI: -0.003, 0.19; p = 0.05) but not in the older group (>70 years; SDM
      = 0.03, 95%CI: -0.05, 0.11; p = 0.48). The meta-regression showed that duration
      of follow up was not associated with changes in cognitive estimates (beta =
      0.005; p = 0.30). CONCLUSIONS: Age appears to modify the association between MetS
      and cognitive decline. These results emphasize the importance of age-stratified
      risk prediction models of dementia in subjects with chronic metabolic disorders.

PMID- 24577477
TI  - Influence of anesthetics on Alzheimer's disease: biophysical, animal model, and
      clinical reports.
AB  - Since the finding in the 1880 s that elderly patients may experience cognitive
      decline following surgery, the search for an understanding of this phenomenon has
      been underway. In the last decade, evidence from biophysical (light scattering
      and nuclear magnetic resonance), in vitro, in vivo animal studies, retrospective
      evaluations of human registries, and recently prospective randomized trials have
      explored the idea that various anesthetic agents play a role in this phenomenon
      by interacting with the biochemical mechanisms that are also responsible for the
      development of Alzheimer's disease. In the current review, we examine the
      evidence available and conclude that there is significant evidence to suggest an
      important role for this mechanism. 

PMID- 24577476
TI  - Fractional anisotropy changes in Alzheimer's disease depend on the underlying
      fiber tract architecture: a multiparametric DTI study using joint independent
      component analysis.
AB  - Diffusion tensor imaging (DTI) allows the simultaneous measurement of several
      diffusion indices that provide complementary information on the substrate of
      white matter alterations in neurodegenerative diseases. These indices include
      fractional anisotropy (FA) as measure of fiber tract integrity, and the mode of
      anisotropy (Mode) reflecting differences in the shape of the diffusion tensor. We
      used a multivariate approach based on joint independent component analysis of FA
      and Mode in a large sample of 138 subjects with Alzheimer's disease (AD)
      dementia, 37 subjects with cerebrospinal fluid biomarker positive mild cognitive
      impairment (MCI-AD), and 153 healthy elderly controls from the European DTI Study
      on Dementia to comprehensively study alterations of microstructural white matter
      integrity in AD dementia and predementia AD. We found a parallel decrease of FA
      and Mode in intracortically projecting fiber tracts, and a parallel increase of
      FA and Mode in the corticospinal tract in AD patients compared to controls.
      Subjects with MCI-AD showed a similar, but spatially more restricted pattern of
      diffusion changes. Our findings suggest an early axonal degeneration in
      intracortical projecting fiber tracts in dementia and predementia stages of AD.
      An increase of Mode, parallel to an increase of FA, in the corticospinal tract
      suggests a more linear shape of diffusion due to loss of crossing fibers along
      relatively preserved cortico-petal and cortico-fugal fiber tracts in AD.
      Supporting this interpretation, we found three populations of fiber tracts,
      namely cortico-petal and cortico-fugal, commissural, and intrahemispherically
      projecting fiber tracts, in the peak area of parallel FA and Mode increase. 

PMID- 24577478
TI  - Metallothioneins and the central nervous system: from a deregulation in
      neurodegenerative diseases to the development of new therapeutic approaches.
AB  - Metallothioneins (MT) are a family of proteins actively involved in metal
      detoxification and storage as well as in prevention of free-radical damage.
      Changes in the levels of MT have been described in a number of neurodegenerative
      diseases including Alzheimer's disease, Parkinson's disease, prion protein
      disease, Binswanger type of subcortical vascular dementia, and amyotrophic
      lateral sclerosis. This suggests that MT functions might be more complex and vast
      than what was initially thought. In this review, we summarize the current
      knowledge on the potential involvement of MT in the mentioned neurodegenerative
      diseases while also discussing the emerging evidence proposing MT modulation as a
      feasible therapeutic approach. Enhancing repair mechanisms after neurological
      damage and/or protection against oxidative stress through a proper modulation of
      this family of protein might indeed represent an important avenue to cope
      neurodegeneration. 

PMID- 24577479
TI  - Selenomethionine ameliorates cognitive decline, reduces tau hyperphosphorylation,
      and reverses synaptic deficit in the triple transgenic mouse model of Alzheimer's
      disease.
AB  - Disruption of the intracellular balance between free radicals and the antioxidant
      system is a prominent and early feature in the neuropathology of Alzheimer's
      disease (AD). Selenium, a vital trace element with known antioxidant potential,
      has been reported to provide neuroprotection through resisting oxidative damage
      but its therapeutic effect on AD remains to be investigated. The objective of our
      study was to investigate the potential of selenomethionine (Se-Met), an organic
      form of selenium, in the treatment of cognitive dysfunction and neuropathology of
      triple transgenic AD (3 * Tg-AD) mice. 3 * Tg-AD mice, which were four months
      old, were treated with Se-Met for 3 months and demonstrated significant
      improvements in cognitive deficit along with an increased selenium level compared
      with the untreated control mice. Se-Met treatment significantly reduced the level
      of total tau and phosphorylated tau, mitigated the decrease of synaptic proteins
      including synaptophysin and postsynaptic density protein 95 in the hippocampus
      and cortex of the 3 * Tg-AD mice. Meanwhile, glial activation in AD mice was
      inhibited and the level of reduced glutathione was increased in the treated mice
      compared with control mice. Additionally, the expression and activity of glycogen
      synthase kinase 3beta and protein phosphatase 2A, two important enzymes involved
      in tau phosphorylation, were markedly decreased and increased respectively by Se
      Met treatment. Thus Se-Met improves cognitive deficit in a murine model of AD,
      which is associated with reduction in tau expression and hyperphosphorylation,
      amelioration of inflammation, and restoration of synaptic proteins and
      antioxidants. This study provides a novel therapeutic approach for the prevention
      of AD. 

PMID- 24577480
TI  - Human brain networks in cognitive decline: a graph theoretical analysis of
      cortical connectivity from EEG data.
AB  - The aim of this study was to investigate the neuronal network characteristics in
      physiological and pathological brain aging. A database of 378 participants
      divided in three groups was analyzed: Alzheimer's disease (AD), mild cognitive
      impairment (MCI), and normal elderly (Nold) subjects. Through EEG recordings,
      cortical sources were evaluated by sLORETA software, while graph theory
      parameters (Characteristic Path Length lambda, Clustering coefficient gamma, and
      small-world network sigma) were computed to the undirected and weighted networks,
      obtained by the lagged linear coherence evaluated by eLORETA software. EEG
      cortical sources from spectral analysis showed significant differences in delta,
      theta, and alpha 1 bands. Furthermore, the analysis of eLORETA cortical
      connectivity suggested that for the normalized Characteristic Path Length
      (lambda) the pattern differences between normal cognition and dementia were
      observed in the theta band (MCI subjects are find similar to healthy subjects),
      while for the normalized Clustering coefficient (gamma) a significant increment
      was found for AD group in delta, theta, and alpha 1 bands; finally, the small
      world (sigma) parameter presented a significant interaction between AD and MCI
      groups showing a theta increase in MCI. The fact that AD patients respect the MCI
      subjects were significantly impaired in theta but not in alpha bands connectivity
      are in line with the hypothesis of an intermediate status of MCI between normal
      condition and overt dementia. 

PMID- 24577481
TI  - Expanded review criteria: the case of nonpharmacological interventions in
      dementia.
AB  - This paper challenges the assumptions underlying many reviews and offers
      alternative criteria for examining evidence for nonpharmacological interventions.
      We evaluated 27 reviews examining interventions for persons with dementia as they
      relate to the issues of selection based on randomized controlled trial (RCT)
      design. Reviews were described by type of intervention, level of cognitive
      function, and criteria for inclusion. Of the 27 reviews, 46% required RCTs for
      inclusion and most had stringent inclusion criteria. This resulted in poor
      utilization of the literature and low ecological validity. Eliminating most of
      the available data poses a critical problem to clinical and research development.
      Studies meeting strict methodological criteria may not generalize to the greater
      population or may exclude sub-populations and interventions. Limitations of
      double-blind RCTs and potential design solutions are set forth based on
      appropriate populations, problems, interventions, and settings characteristics. 

PMID- 24577482
TI  - The impact of surgery and anesthesia on post-operative cognitive decline and
      Alzheimer's disease development: biomarkers and preventive strategies.
AB  - Alzheimer's disease (AD) is a major social and clinical burden in the elderly,
      affecting 5% of people aged over 65 and 20% aged over 80. Despite improved
      management, a cure has not been found and hence analysis of predisposing factors
      to identify preventive strategies has become increasingly important. Surgery and
      anesthesia have been proposed to increase the incidence of post-operative
      cognitive decline (POCD) and AD. This is hypothesized to be the result of a
      malignant neuroinflammatory response and subsequent synaptic impairment in the
      elderly and susceptible individuals. As a result, strategies are being explored
      to prevent surgery and anesthesia induced cognitive impairment. Whereas
      previously the diagnosis of AD was primarily dependent on clinical examination,
      biomarkers such as inflammatory cytokines, amyloid-beta, and tau deposition in
      the cerebrospinal fluid have received increased attention. Nonetheless, AD is
      currently still treated symptomatically with acetylcholinesterase inhibitors and
      NMDA antagonists to improve cholinergic transmission and prevent glutamatergic
      excitotoxicity. Therapeutic success is, however, often not achieved, since these
      treatment methods do not address the ongoing neuroinflammatory processes and
      hence novel therapeutic and protective strategies are urgently needed. This
      review provides an insight into the current understanding of age-related
      cognitive impairment post-surgery and reflects on novel markers of AD
      pathogeneses exploring their use as targets for treatment. It gives a summary of
      recent efforts in preventing and treating POCD or AD with regards to the choice
      and depth of anesthesia, surgical strategy, and peri-operative medication, and
      discusses the mechanism of action and therapeutic prospects of novel agents. 

PMID- 24577483
TI  - Outcomes of mandibular distraction osteogenesis in the treatment of severe
      micrognathia.
AB  - IMPORTANCE: Patients with severe micrognathia are predisposed to airway
      obstruction. Mandibular distraction osteogenesis (MDO) is an alternative to
      tracheotomy that lengthens the mandible in order to improve the retrolingual
      airway. This study presents outcomes from one of the largest cohorts reported.
      OBJECTIVE: To assess the rate and predictors of surgical success and
      complications among (1) patients who underwent MDO prior to other airway
      procedures (MDO first), and (2) patients who required an initial tracheotomy and
      were subsequently treated with MDO (tracheotomy first). DESIGN, SETTING, AND
      PARTICIPANTS: Retrospective cohort study at a tertiary care pediatric medical
      center of patients diagnosed as having micrognathia resulting in symptomatic
      airway obstruction (Pierre Robin sequence) and who underwent MDO from September
      1995 to December 2009. INTERVENTIONS: Electronic medical records were reviewed.
      Multivariable regression analysis was used to assess for predictors of outcome.
      MAIN OUTCOMES AND MEASURES: Rates of surgical success (defined as either
      tracheotomy avoidance or decannulation) and complications. Potential predictors
      included demographics, syndrome presence, follow-up time, and surgical history.
      RESULTS: A total of 123 patients (61 in MDO-first subgroup, 62 in tracheotomy
      first subgroup) underwent MDO during the study period. Median age at time of
      distraction was 21 months (range, 7 days-24 years). Surgical success and
      complication rates were 83.6% and 14.8% in the MDO-first subgroup and 67.7% and
      38.7% in the tracheotomy-first subgroup. Tracheotomy-first patients were more
      likely to have a syndromic diagnosis (66.0% vs 43.0%; P = .009) and were older at
      the time of MDO (median age, 30 months vs 5.1 months; P < .001). Poorer odds of
      success were associated with the need for 2 or more other airway procedures (odds
      ratio [OR], 0.14 [95% CI, 0.02-0.82]) in the MDO-first subgroup and craniofacial
      microsomia or Goldenhar syndrome (OR, 0.07 [95% CI, 0.009-0.52]) in the
      tracheotomy-first subgroup. CONCLUSIONS AND RELEVANCE: Mandibular distraction
      osteogenesis has a high rate of success in avoiding tracheotomy. Patients who
      required a tracheotomy before MDO had a lower success rate in achieving
      decannulation and a higher rate of complications. However, these patients also
      had a higher rate of syndromic diagnoses and associated comorbidities. Patients
      with Goldenhar syndrome have a decreased likelihood of surgical success.

PMID- 24577484
TI  - Improved site-specific recombinase-based method to produce selectable marker- and
      vector-backbone-free transgenic cells.
AB  - PhiC31 integrase-mediated gene delivery has been extensively used in gene therapy
      and animal transgenesis. However, random integration events are observed in
      phiC31-mediated integration in different types of mammalian cells; as a result,
      the efficiencies of pseudo attP site integration and evaluation of site-specific
      integration are compromised. To improve this system, we used an attB-TK fusion
      gene as a negative selection marker, thereby eliminating random integration
      during phiC31-mediated transfection. We also excised the selection system and
      plasmid bacterial backbone by using two other site-specific recombinases, Cre and
      Dre. Thus, we generated clean transgenic bovine fetal fibroblast cells free of
      selectable marker and plasmid bacterial backbone. These clean cells were used as
      donor nuclei for somatic cell nuclear transfer (SCNT), indicating a similar
      developmental competence of SCNT embryos to that of non-transgenic cells.
      Therefore, the present gene delivery system facilitated the development of gene
      therapy and agricultural biotechnology. 

PMID- 24577485
TI  - Efficacy and safety of edoxaban in comparison with dabigatran, rivaroxaban and
      apixaban for stroke prevention in atrial fibrillation. An indirect comparison
      analysis.
AB  - Large Phase 3 clinical trials for stroke prevention in atrial fibrillation (AF)
      have compared non-vitamin K antagonist oral anticoagulants (NOACs) against
      warfarin, with the edoxaban trial only recently reported. In the absence of head
      to head trials directly comparing these NOACs against each other, we compared the
      efficacy and safety of edoxaban to other agents by an indirect comparison
      analysis. We performed an indirect comparison analysis of edoxaban (2 dose
      strategies) against apixaban (1 dose), dabigatran etexilate (2 doses) and
      rivaroxaban (1 dose), for their relative efficacy and safety against each other.
      For high-dose edoxaban vs apixaban, there were no significant differences in
      efficacy endpoints, mortality, myocardial infarction and major bleeding. Apixaban
      was associated with less major or clinically relevant non-major bleeding (hazard
      ratio [HR] 0.79; 95% confidence interval [CI] 0.70-0.90) and gastrointestinal
      bleeding (HR 0.72; 95% CI 0.53-0.99). For dabigatran 110 mg twice daily, there
      were no significant differences in the main efficacy or safety endpoints.
      Dabigatran 150 mg bid was associated with lower stroke/systemic embolism (SE) (HR
      0.75; 95% CI 0.56-0.99), stroke (HR 0.73; 95% CI 0.55-0.96) and haemorrhagic
      stroke (HR 0.48; 95% CI 0.23-0.99). There were no significant differences between
      high-dose edoxaban vs rivaroxaban for efficacy endpoints or mortality, but
      rivaroxaban had more major and/or clinically relevant non-major bleeding. When
      compared to low-dose edoxaban, apixaban was associated with lower stroke/SE (HR
      0.70; 95% CI 0.55-0.89), stroke (HR 0.70; 95% CI 0.55-0.92) and ischaemic stroke
      (HR 0.65; 95% CI 0.50-0.89), but more major bleeding (HR 1.47; 95% CI 1.20-1.80).
      For dabigatran 110 mg bid, there were no significant differences in the efficacy
      endpoints, but dabigatran 110 mg bid had higher major (and gastrointestinal)
      bleeding. Dabigatran 150 mg bid and rivaroxaban were associated with lower
      stroke/SE and ischaemic stroke, but higher bleeding rates. In the present
      analysis, we have provided for the first time, comparisons of efficacy and safety
      of edoxaban against other NOACs. Notwithstanding the significant limitations of
      an indirect comparison analysis, some differential effects are evident with the
      NOACs for stroke prevention, allowing us to allow the prescriber a 'choice' to be
      able to fit the drug to the patient clinical profile (and vice versa). 

PMID- 24577486
TI  - Exogenous Boron supplementation partially rescues fertilization defect of osbor4
      mutant.
AB  - Arabidopsis thaliana BOR1 is the first boron (B) transporter identified in the
      living systems. In the rice genome, there are four AtBOR1-like genes, OsBOR1, 2,
      3 and 4. We have previously demonstrated that OsBOR4 is a B efflux transporter
      gene specifically expressed in rice pollen. OsBOR4 heterozygous lines showed
      abnormal segregation ratio, suggesting the significance of OsBOR4 in rice pollen
      tube germination/elongation process. To obtain further insights into the
      mechanisms underlying fertilization defects by osbor4 mutations, we examined if
      the mutant pollen exhibits morphological changes. The cross section of the pollen
      of the mutant was similar to those of the wild type. We also determined B
      concentrations in brown rice of three osbor4 mutants and found that B levels were
      comparable. These results suggest that osbor4 mutation does not affect B
      transport to pollen and seeds. We then examined if exogenous B supplementation
      can rescue segregation defect of osbor4. As reported previously, a OsBOR4
      heterozygous lines showed abnormal segregation rate under the normal growth
      condition in this present study, too. Importantly, this abnormality in
      segregation was partially rescued by application of six-times higher B
      concentration to roots, providing further evidence that the fertilization defect
      of osbor4 is due to the defect in B transport process. Taken together we propose
      that osbor4 causes defect in B transport process during pollen germination to
      fertilization. 

PMID- 24577488
TI  - Effects of extruded whole maize, polydextrose and cellulose as sources of fibre
      on calcium bioavailability and metabolic parameters of growing Wistar rats.
AB  - The aim of this study was to evaluate the influence of diets with different types
      of fibres on Ca bioavailability and metabolic parameters in growing Wistar rats.
      Twenty four male Wistar rats were fed with 3 different diets: control (C),
      polydextrose (PD), and extruded whole maize (M) during a 60 day period. Apparent
      Ca absorption percentage (%Ca Abs), total skeleton bone mineral content (t BMC),
      total bone mineral density (t BMD), femur (F), spine (S) and tibia (T) BMD, cecum
      weight, and pH were evaluated. Malondialdehyde (MDA) and lipid (TG and
      cholesterol) contents in serum and liver were also evaluated. The results showed
      that rats fed with M and PD had the same cecum weight, but higher than that of C
      (1.53 +/- 0.02 vs. 0.94 +/- 0.01). There was moderate acidification of the cecal
      content in rats fed with M compared to C (pH 5.93 vs. 6.98) and the fecal weight
      was 1.06 +/- 0.02, 3.07 +/- 0.03 and 4.81 +/- 0.05 for PD, M and C, respectively.
      There were significant differences in %Ca Abs between PD and C (87.57 +/- 1.20
      vs. 71.10 +/- 1.11). The PD group had the highest values of F-BMD, S-BMD, and T
      BMD, but there were no differences between M and C groups. Regarding lipids,
      there was a significant lowering effect in the M liver triglycerides content.
      Moreover, liver MDA levels significantly decreased with M and PD diets. The
      consumption of PD and grain fibres can exert some beneficial gastrointestinal
      effects such as lowering of the pH, hepatic TG and MDA content related to fibre
      colon fermentation.

PMID- 24577489
TI  - [Letter to the Editor regarding the article "Evaluation of complete Freund's
      adjuvant-induced arthritis in a Wistar rat model"].

PMID- 24577490
TI  - [Recipes systemic lupus erythematosus].

PMID- 24577494
TI  - Hypomagnesemia in hemodialysis patients: role of proton pump inhibitors.
AB  - BACKGROUND: Recent observations have associated hypomagnesemia with increased
      risk of cardiovascular morbidity and mortality in hemodialysis patients. METHODS:
      We did a 3-month chart review of 62 chronic hemodialysis patients at a single US
      hospital. All were dialyzed using a dialysate [Mg] of 0.75-1.0 mEq/l. Patients
      were divided into two groups: hypomagnesemic (mean predialysis plasma [Mg] <1.5
      mEq/l) and non-hypomagnesemic (mean predialysis plasma [Mg] >=1.5 mEq/l).
      RESULTS: All patients were male; mean age was 64.3 +/- 8.7 years and the majority
      (73%) diabetic. 24 patients (39%) had hypomagnesemia and 38 (61%) were not
      hypomagnesemic. There were no significant differences between the two groups in
      age, diabetes status, blood pressure, duration of dialysis, plasma calcium,
      phosphorus, albumin, intact parathyroid hormone (PTH), dialysis adequacy (Kt/V),
      or dietary protein intake (as estimated by normalized protein catabolic rate,
      nPCR). However, use of proton pump inhibitors (PPIs) was significantly associated
      with hypomagnesemia (plasma [Mg] 1.48 +/- 0.16 mEq/l in the PPI group vs. 1.65 +/
      0.26 mEq/l in the non-PPI group, p = 0.007). Adjustment for age, diabetes
      status, duration of dialysis, plasma albumin, Kt/V, nPCR, and diuretic use did
      not affect the association between PPI use and hypomagnesemia. CONCLUSIONS: Use
      of PPIs in patients dialyzed using a dialysate [Mg] of 0.75-1.0 mEq/l is
      associated with hypomagnesemia. We suggest monitoring plasma [Mg] in patients
      taking PPIs, with discontinuation of the medication if possible and/or adjustment
      of dialysate [Mg] to normalize plasma [Mg].

PMID- 24577496
TI  - Dynamic combinatorial chemistry with diselenides and disulfides in water.
AB  - Diselenide exchange is introduced as a reversible reaction in dynamic
      combinatorial chemistry in water. At neutral pH, diselenides are found to mix
      with disulfides and form dynamic combinatorial libraries of diselenides,
      disulfides, and selenenylsulfides. 

PMID- 24577495
TI  - Vitamin D and risk of postoperative hypocalcemia after total thyroidectomy.
AB  - IMPORTANCE: Transient hypocalcemia is a well-recognized occurrence after total
      thyroidectomy. It has been hypothesized that underlying vitamin D deficiency may
      increase the risk of this complication, although to date there are few data in
      the literature supporting this hypothesis. OBJECTIVE: To investigate whether
      perioperative vitamin D levels have any effect on postthyroidectomy hypocalcemia.
      DESIGN, SETTING, AND PARTICIPANTS: We performed a retrospective review of a
      prospectively maintained database of thyroidectomies from November 1, 2009,
      through September 30, 2012, at an academic teaching hospital. The study included
      121 patients with available vitamin D levels undergoing total or completion
      thyroidectomy. Patients with preexisting hypercalcemia or hyperparathyroidism
      were excluded. INTERVENTIONS: All patients underwent total removal of all thyroid
      tissue by a capsular dissection technique. Routine calcium or vitamin D
      supplementation was not administered. Biochemical hypocalcemia was defined as any
      single postoperative corrected calcium level less than 8.0 mg/dL (to convert to
      millimoles per liter, multiply by 0.25) and symptomatic hypocalcemia as any
      symptoms of hypocalcemia. MAIN OUTCOMES AND MEASURES: Outcome measures were
      incidence of postoperative hypocalcemia and association with vitamin D levels. A
      multivariate analysis was performed to study the effect of other variables,
      including performance of central neck dissection, incidental parathyroidectomy,
      and hyperthyroidism, on the incidence of postoperative hypocalcemia. RESULTS: The
      incidence of transient biochemical hypocalcemia was 24% (n = 29/121). There was
      no correlation between vitamin D levels and risk of postoperative hypocalcemia.
      On univariate analysis, performance of concomitant central compartment neck
      dissection revealed an increased risk of hypocalcemia (P = .06), but this finding
      was not significant on multivariate analysis. CONCLUSIONS AND RELEVANCE: Vitamin
      D levels do not appear to have a significant effect on the risk of
      postthyroidectomy hypocalcemia.

PMID- 24577497
TI  - Clonality and anatomic distribution on the skin of antibiotic resistant and
      sensitive Propionibacterium acnes.
AB  - Increasing antibiotic resistance in the population of Propionibacterium acnes is
      a major concern. Our aims were to examine the clonal relationships and anatomical
      distribution of resistant and sensitive P. acnes. A collection of 350 P. acnes
      isolates was therefore used to determine the minimum inhibitory concentration of
      tetracycline, erythro-mycin and clindamycin, multilocus sequence type, and the
      identity of genetic resistance markers. Two hitherto unknown resistance mutations
      were detected. Resistant P. acnes mainly belonged to clonal clusters in division
      I-1a frequently isolated from skin and associated with moderate to severe acne.
      All high-level tetracycline resistant strains were members of a single clone.
      Multiple isolates from distinct anatomic areas of surface skin and follicles of 2
      acne patients revealed substantial clonal diversity between areas and co
      existence of resistant and sensitive clones. Fifty-two percent of Danish acne
      patients and 43% of controls carried at least one resistant P. acnes strain,
      resistance to clindamycin being most frequent followed by tetracycline and
      erythromycin. Resistance to tetracycline was detected exclusively among isolates
      from acne patients. In conclusion, antibiotic resistance is associated with
      particular evolutionary clades of P. acnes and a substantial part is due to a
      single geographically widespread clone (ST3). Individuals carry a strikingly
      complex population of P. acnes with distinct virulence potential and antibiotic
      resistance.

PMID- 24577501
TI  - An efficient nano-composite layer for highly transparent organic light emitting
      diodes.
AB  - We report highly transparent and low resistive new cathode structures, which
      basically consist of nano-composite layer/Ag/WO3 for transparent organic light
      emitting diode (TOLED) applications. Our new cathode structure exhibits an
      extremely high transmittance of 91.2% at 550 nm, a low sheet resistance of 5.4
      Omega ?(-1), and excellent electron injection properties. Such a high
      transmittance along with a low resistivity of the fabricated new cathode could be
      explained by surface-modifying behavior with the generation of a nano-composite
      thin silver oxide layer during Ag deposition. Chemical interaction at the
      interface between the electron injection layer and the electron transport layer
      results in good electron injection properties in TOLEDs. The fabricated TOLEDs
      with our new cathode structures have a full device transmittance of 85-87% at 550
      nm. 

PMID- 24577502
TI  - Freezing of gait and falls in Parkinson's disease.
AB  - Freezing of gait (FOG) and falls are common and disabling phenomena in
      Parkinson's disease (PD) and related disorders as they may lead to loss of
      independence. Both are usually observed in the advanced stage of the disease,
      although they can also be seen in the early stage. FOG and falls have similar
      risk factors, such as axial motor disability and cognitive impairment, and FOG is
      one of the most common causes of falls. The objective of this review is to
      address recent ideas about the underlying pathophysiology of FOG and falls, and
      discuss the similarities, differences, and relationships between FOG and falls.
      Recent advances in studies that elucidate physical and cognitive risk factors to
      predict future falls are also reviewed. In addition to the history of prior falls
      and disease severity, the presence of FOG and cognitive dysfunction are
      associated with falls in PD. 

PMID- 24577500
TI  - STAT3 activation by KSHV correlates with IL-10, IL-6 and IL-23 release and an
      autophagic block in dendritic cells.
AB  - Kaposis's sarcoma associated herpesvirus (KSHV) has been reported to infect,
      among others, monocytes and dendritic cells DCs impairing their function.
      However, the underlying mechanisms remain not completely elucidated yet. Here we
      show that DC exposure to active or UV-inactivated KSHV resulted in STAT3
      phosphorylation. This effect, partially dependent on KSHV-engagement of DC-SIGN,
      induced a high release of IL-10, IL-6 and IL-23, cytokines that in turn might
      maintain STAT3 in a phosphorylated state. STAT3 activation also correlated with a
      block of autophagy in DCs, as indicated by LC3II reduction and p62 accumulation.
      The IL-10, IL-6 and IL-23 release and the autophagic block could be overcome by
      inhibiting STAT3 activation, highlighting the role of STAT3 in mediating such
      effects. In conclusion, here we show that STAT3 activation can be one of the
      molecular mechanisms leading to KSHV-mediated DC dysfunction, that might allow
      viral persistence and the onset of KSHV-associated malignancies. 

PMID- 24577503
TI  - MRI can detect nigral volume loss in patients with Parkinson's disease: evidence
      from a meta-analysis.
AB  - BACKGROUND: Parkinson's disease (PD) involves the degeneration of dopaminergic
      neurons in substantia nigra (SN) compacta. However, it is still a contentious
      issue whether magnetic resonance imaging (MRI) can detect the nigral volume loss
      in PD patients. OBJECTIVE: We synthesized the results of published research on SN
      volumetry using a meta-analysis method in order to clarify this issue. METHODS: A
      comprehensive literature search yielded 8 eligible studies. Nigral size was
      expressed as the standardized mean difference (SMD) between normal controls and
      PD patients. In addition, subgroup analysis was performed in order to identify
      the best condition for nigral volumetry. The proportion of variation due to
      heterogeneity was computed and expressed as I2. RESULTS: Eight studies involved
      172 normal control and 193 PD patients. The overall effect indicated that nigral
      volume in PD was significantly smaller than normal controls with homogeneous
      studies (SMD = -0.65, P < 0.0001; I2 = 47%). Maximum of subgroup effect was
      observed in 'volumetry' among three approaches ('thickness': SMD = -0.35, P =
      0.18, I2 = not available; 'area': SMD = -0.39, P = 0.14, I2 = 0%; 'volumetry':
      SMD = -0.82, P = 0.0006, I2 = 56%). The approach including T1-weighted images
      (T1WI) showed larger effect ('with T1WI': SMD = -1.11, P < 0.00001, I2 = 36%;
      'without T1WI': SMD = -0.32, P = 0.04, I2 = 0%). CONCLUSIONS: These findings
      suggest that volumetry based on T1WI could be the most sensitive option to
      identify nigral volume loss in PD patients.

PMID- 24577504
TI  - Sudomotor and cardiovascular dysfunction in patients with early untreated
      Parkinson's disease.
AB  - BACKGROUND: According to Braak staging of Parkinson's disease (PD), detection of
      autonomic dysfunction would help with early diagnosis of PD. OBJECTIVE: To
      determine whether the autonomic nervous system is involved in the early stage of
      PD, we evaluated cardiovascular and sudomotor function in early untreated PD
      patients. METHODS: Orthostatic blood pressure regulation, heart rate variability,
      skin vasomotor function, and palmar sympathetic sweat responses were examined in
      50 early untreated PD patients and 20 healthy control subjects. RESULTS: The mean
      decrease in systolic blood pressure during head-up tilt in PD patients was mildly
      but significantly larger than in controls (p = 0.0001). There were no differences
      between the 2 groups in heart rate variability, with analysis of low frequency
      (LF; mediated by baroreflex feedback), and high frequency (HF; mainly reflecting
      parasympathetic vagal) modulation. However, LF/HF, an index of sympatho
      parasympathetic balance, was lower in the PD group than in controls (p = 0.02).
      Amplitudes of palmar sweat responses to deep inspiration (p = 0.004), mental
      arithmetic (p = 0.01), and exercise (p = 0.01) in PD patients were lower than in
      controls, with negative correlations with motor severity. Amplitudes of palmar
      skin vasomotor reflexes in PD patients did not differ from controls. CONCLUSIONS:
      Our study indicates impairment of sympathetic cardiovascular and sudomotor
      function with orthostatic dysregulation of blood pressure control, reduced LF/HF
      and reduction in palm sweat responses even in early untreated PD patients.

PMID- 24577506
TI  - An uncommon surgical disease.

PMID- 24577505
TI  - Estimating the burden of hospitalization for pneumococcal pneumonia in a general
      population aged 50 years or older and implications for vaccination strategies.
AB  - Streptococcus pneumoniae is a major cause of human infectious diseases worldwide.
      Despite this documented evidence, data on pneumococcal disease rates among
      general populations are scant because of the frequent lack of cultural
      identification. In this study we propose a model for estimating the burden of
      pneumococcal pneumonia on hospitalizations. The study was performed by analyzing
      administrative and clinical data of patients aged 50 years or older, resident in
      Sicily, and hospitalized, from 2005 to 2012. Demographic information,
      admission/discharge dates, discharge status, and up to 6 discharge diagnoses
      coded according to ICD-9 CM were collected for each hospitalized patient. During
      the 8-year study period, a total of 72,372 hospitalizations with at least one ICD
      9 CM diagnosis code suggestive of all-cause pneumonia were recorded. Of these,
      1943 (2.7%) hospitalizations had specific ICD-9 CM diagnosis codes for
      pneumococcal pneumonia. According to the proposed model, 16,541 (22.9%) pneumonia
      out of all-cause pneumonia was estimated to be attributable to S. pneumoniae.
      Pneumococcal pneumonia and model-estimated pneumococcal pneumonia had mean
      hospitalization rates of 13.4 and 113.3/100,000, respectively, with a decreasing
      temporal trend. The risk of hospitalization for pneumococcal pneumonia was
      strongly correlated with age (P<0.001). Our model provides data usable to
      construct suitable decisional models for the decision-makers and could allow to
      the responsibles of healthcare facilities to assess the budget impact if they
      hypothesize to offer vaccination for pneumococcal disease to certain cohorts of
      subjects aged 50 years or older. In our area, the high estimated hospitalization
      rates among adults aged >=65 years suggest the need to implement effective
      preventive strategies (e.g., vaccination) tailored for these groups.

PMID- 24577509
TI  - Incidental mandibular lesion in a patient with head and neck cancer.

PMID- 24577508
TI  - Activation of Type 3 innate lymphoid cells and interleukin 22 secretion in the
      lungs during Streptococcus pneumoniae infection.
AB  - Mucosal sites are continuously exposed to pathogenic microorganisms and are
      therefore equipped to control respiratory infections. Type 3 innate lymphoid
      cells (ILC3) are key players in antimicrobial defense in intestinal mucosa,
      through interleukin 17 and interleukin 22 (IL-22) production. The present study
      aimed at analyzing the distribution and function of ILC3 in the respiratory
      tract. We first observed that lung mucosa harbors a discrete population of ILC3
      expressing CD127, CD90, CCR6, and the transcriptional factor RORgammat. In
      addition, lung ILC3 were identified as a major source of IL-22 in response to
      interleukin 23 stimulation. During Streptococcus pneumoniae infection, ILC3
      rapidly accumulated in the lung tissue to produce IL-22. In response to S.
      pneumoniae, dendritic cells and MyD88, an important adaptor of innate immunity,
      play critical functions in IL-22 production by ILC3. Finally, administration of
      the Toll-like receptor 5 agonist flagellin during S. pneumoniae challenge
      exacerbated IL-22 production by ILC3, a process that protects against lethal
      infection. In conclusion, boosting lung ILC3 might represent an interesting
      strategy to fight respiratory bacterial infections.

PMID- 24577507
TI  - Membrane-associated proteomics of chickpea identifies Sad1/UNC-84 protein
      (CaSUN1), a novel component of dehydration signaling.
AB  - Dehydration affects almost all the physiological processes including those that
      result in the accumulation of misfolded proteins in the endoplasmic reticulum
      (ER), which in turn elicits a highly conserved signaling, the unfolded protein
      response (UPR). We investigated the dehydration-responsive membrane-associated
      proteome of a legume, chickpea, by 2-DE coupled with mass spectrometry. A total
      of 184 protein spots were significantly altered over a dehydration treatment of
      120 h. Among the differentially expressed proteins, a non-canonical SUN domain
      protein, designated CaSUN1 (Cicer arietinum Sad1/UNC-84), was identified. CaSUN1
      localized to the nuclear membrane and ER, besides small vacuolar vesicles. The
      transcripts were downregulated by both abiotic and biotic stresses, but not by
      abscisic acid treatment. Overexpression of CaSUN1 conferred stress tolerance in
      transgenic Arabidopsis. Furthermore, functional complementation of the yeast
      mutant, slp1, could rescue its growth defects. We propose that the function of
      CaSUN1 in stress response might be regulated via UPR signaling.

PMID- 24577510
TI  - Histone deacetylase inhibitor prevents cell growth in Burkitt's lymphoma by
      regulating PI3K/Akt pathways and leads to upregulation of miR-143, miR-145, and
      miR-101.
AB  - Burkitt lymphoma (BL) is an aggressive B-cell lymphoma more common in children
      comprising one third of pediatric non-Hodgkin lymphoma cases. The recent
      discovery in BL pathogenesis highlighted the activation of PI3K pathway in
      cooperation with Myc in the development of BL. In this study, we demonstrated
      that PI3K/Akt pathway is a target to histone deacetylase inhibitor (HDACi) in BL
      cells. The combination of HDACi (sodium butyrate, NaB) and chemotherapy (VP-16)
      inhibited 51 % of the proliferation and enhanced the blockage of the cell cycle
      progression at G2/M with a concurrent decrease in the S phase. Microarray
      profiling showed a synergistic action of NaB/VP-16 combination through the
      differential regulation of 1,413 genes. Comparing VP-16 treatment with the NaB/VP
      16 combination, 318 genes were deregulated: 250 genes were downregulated, and 68
      were upregulated when compared with untreated cells. Among these genes, six
      (CDKN1A, CCND1, FAS, CHEK2, MDM4, and SESN2) belong to the p53-signaling pathway.
      The activation of this signaling pathway is usually induced by stress signals and
      ultimately leads to cell cycle arrest. Besides, the inhibition of the cell growth
      was related to reduced Akt phosphorylation, and decrease of c-Myc protein
      expression by about 60 % (p <= 0.005). Moreover, HDACi enhanced miR-101, miR-143,
      and miR-145 levels in BL cell line, which were inversely associated with the
      levels of miR-101, miR-143, and miR-145 found to be extremely downregulated in
      the sample of BL patients. We highlight the fact that effective combinations of
      HDACis with other target drugs could improve BL therapy in the future. 

PMID- 24577511
TI  - G-CSF induces the release of the soluble form of LR11, a regulator of myeloid
      cell mobilization in bone marrow.
AB  - Granulocyte colony-stimulating factor (G-CSF) induces the mobilization of
      leukocytes from the bone marrow (BM) to the circulation by a yet incompletely
      understood mechanism. Here, we describe that the membrane-bound receptor LR11 is
      highly expressed in human myeloid cells and that the shed soluble form of LR11
      (sLR11) is a modifier of myeloid cell migration. In the process of leukocyte
      mobilization by G-CSF treatment, circulating sLR11 levels are transiently
      elevated in humans and mice. Moreover, following G-CSF treatment, the sLR11
      levels in patients show significant positive correlation with the numbers of
      mobilized leukocytes. The changes of LR11 levels in BM cells and of sLR11
      released into the BM fluid of mice correlate tightly with the changes in
      circulating sLR11 levels. G-CSF dose-dependently enhanced sLR11 release from HL
      60 cells, which in turn accelerated cell migration. Finally, cooperatively with
      tumor necrosis factor-alpha (TNF-alpha) and G-CSF, sLR11 increased the attachment
      of floating cells (HL-60 and U937) to endothelial cells. We propose that sLR11 is
      a novel candidate modifier of G-CSF-mediated mobilization of hematologic cells.
      Identification of sLR11 as a regulatory component of G-CSF-mediated hematologic
      cell mobilization may facilitate further improvement of hematologic stem cell
      collection for clinical applications. 

PMID- 24577513
TI  - Novel heterozygous c.798C>G and c.1040T>G mutations in the GBA1 gene are
      associated with a severe phenotype of Gaucher disease type 1.

PMID- 24577512
TI  - Tandem triplication of the BCL2 gene in CD5-positive intravascular large B cell
      lymphoma with bone marrow involvement.

PMID- 24577514
TI  - Elevated tricuspid regurgitant jet velocity in subgroups of thalassemia patients:
      insight into pathophysiology and the effect of splenectomy.
AB  - A high tricuspid regurgitant jet velocity (TRV) signifies a risk for or
      established pulmonary hypertension (PH), which is a serious complication in
      thalassemia patients. The underlying pathophysiology in thalassemia subgroups and
      potential biomarkers for early detection and monitoring are not well defined, in
      particular as they relate to spleen removal. To better understand some of these
      unresolved aspects, we examined 76 thalassemia patients (35 non-transfused), 25
      splenectomized non-thalassemia patients (15 with hereditary spherocytosis), and
      12 healthy controls. An elevated TRV (>2.5 m/s) was found in 25/76 (33 %) of the
      patients, confined to non-transfused or those with a late start of transfusions,
      including patients with hemoglobin H-constant spring, a finding not previously
      described. These non or late-transfused patients (76 % splenectomized) had
      significantly increased platelet activation (sCD40L), high platelet count,
      endothelial activation (endothelin-1), and hemolysis (LDH, plasma-free Hb), while
      hypercoagulable and inflammatory markers were not significantly increased. The
      same markers were increased in the seven patients with confirmed PH on cardiac
      catheterization, suggesting their possible role for screening patients at risk
      for PH. A combination of hemolysis and absence of spleen is necessary for
      developing a high TRV, as neither chronic hemolysis in the non-splenectomized
      thalassemia patients nor splenectomy without hemolysis, in the non-thalassemia
      patients, resulted in an increase in TRV. 

PMID- 24577520
TI  - Enhanced sensitivity of surface acoustic wave-based rate sensors incorporating
      metallic dot arrays.
AB  - A new surface acoustic wave (SAW)-based rate sensor pattern incorporating
      metallic dot arrays was developed in this paper. Two parallel SAW delay lines
      with a reverse direction and an operation frequency of 80 MHz on a same X-112
      degrees Y LiTaO3 wafer are fabricated as the feedback of two SAW oscillators, and
      mixed oscillation frequency was used to characterize the external rotation. To
      enhance the Coriolis force effect acting on the SAW propagation, a copper (Cu)
      dot array was deposited along the SAW propagation path of the SAW devices. The
      approach of partial-wave analysis in layered media was referred to analyze the
      response mechanisms of the SAW based rate sensor, resulting in determination of
      the optimal design parameters. To improve the frequency stability of the
      oscillator, the single phase unidirectional transducers (SPUDTs) and combed
      transducer were used to form the SAW device to minimize the insertion loss and
      accomplish the single mode selection, respectively. Excellent long-term (measured
      in hours) frequency stability of 0.1 ppm/h was obtained. Using the rate table
      with high precision, the performance of the developed SAW rate sensor was
      evaluated experimentally; satisfactory detection sensitivity (16.7 Hz?deg?s(-1))
      and good linearity were observed.

PMID- 24577515
TI  - Chronic cannabidiol treatment improves social and object recognition in double
      transgenic APPswe/PS1?E9 mice.
AB  - RATIONALE: Patients suffering from Alzheimer's disease (AD) exhibit a decline in
      cognitive abilities including an inability to recognise familiar faces. Hallmark
      pathological changes in AD include the aggregation of amyloid-beta (Abeta), tau
      protein hyperphosphorylation as well as pronounced neurodegeneration,
      neuroinflammation, neurotoxicity and oxidative damage. OBJECTIVES: The non
      psychoactive phytocannabinoid cannabidiol (CBD) exerts neuroprotective, anti
      oxidant and anti-inflammatory effects and promotes neurogenesis. CBD also
      reverses Abeta-induced spatial memory deficits in rodents. MATERIALS AND METHODS:
      Thus we determined the therapeutic-like effects of chronic CBD treatment (20
      mg/kg, daily intraperitoneal injections for 3 weeks) on the APPswe/PS1?E9
      (APPxPS1) transgenic mouse model for AD in a number of cognitive tests, including
      the social preference test, the novel object recognition task and the fear
      conditioning paradigm. We also analysed the impact of CBD on anxiety behaviours
      in the elevated plus maze. RESULTS: Vehicle-treated APPxPS1 mice demonstrated
      impairments in social recognition and novel object recognition compared to wild
      type-like mice. Chronic CBD treatment reversed these cognitive deficits in
      APPxPS1 mice without affecting anxiety-related behaviours. CONCLUSIONS: This is
      the first study to investigate the effect of chronic CBD treatment on cognition
      in an AD transgenic mouse model. Our findings suggest that CBD may have
      therapeutic potential for specific cognitive impairments associated with AD.

PMID- 24577521
TI  - On the use of low-cost radar networks for collision warning systems aboard
      dumpers.
AB  - The use of dumpers is one of the main causes of accidents in construction sites,
      many of them with fatal consequences. These kinds of work machines have many
      blind angles that complicate the driving task due to their large size and volume.
      To guarantee safety conditions is necessary to use automatic aid systems that can
      detect and locate the different objects and people in a work area. One promising
      solution is a radar network based on low-cost radar transceivers aboard the
      dumper. The complete system is specified to operate with a very low false alarm
      rate to avoid unnecessary stops of the dumper that reduce its productivity. The
      main sources of false alarm are the heavy ground clutter, and the interferences
      between the radars of the network. This article analyses the clutter for LFM
      signaling and proposes the use of Offset Linear Frequency Modulated Continuous
      Wave (OLFM-CW) as radar signal. This kind of waveform can be optimized to reject
      clutter and self-interferences. Jointly, a data fusion chain could be used to
      reduce the false alarm rate of the complete radar network. A real experiment is
      shown to demonstrate the feasibility of the proposed system. 

PMID- 24577522
TI  - Ground testing strategies for verifying the slew rate tolerance of star trackers.
AB  - The performance of a star tracker is largely based on the availability of its
      attitude solution. Several methods exist to assess star tracker availability
      under both static and dynamic imaging conditions. However, these methods
      typically make various idealizations that can limit the accuracy of these
      results. This study aims to increase the fidelity of star tracker availability
      modeling by accounting for the effects of detection logic and pixel saturation on
      star detection. We achieve this by developing an analytical model for the focal
      plane intensity distribution of a star in the presence of sensor slew. Using the
      developed model, we examine the effects of slew rate on star detection using
      simulations and lab tests. The developed approach allows us to determine the
      maximum slew rate for which a star of a given stellar magnitude can still be
      detected. This information can then be used to describe the availability of a
      star tracker attitude solution as a function of slew rate, both spatially, across
      the entire celestial sphere, or locally, along a specified orientation track. 

PMID- 24577516
TI  - In vitro and in vivo characterisation of Lu AF64280, a novel, brain penetrant
      phosphodiesterase (PDE) 2A inhibitor: potential relevance to cognitive deficits
      in schizophrenia.
AB  - Here, we present the pharmacological characterisation of Lu AF64280, a novel,
      selective, brain penetrant phosphodiesterase (PDE) 2A inhibitor, in in vitro/in
      vivo assays indicative of PDE2A inhibition, and in vivo models/assays relevant to
      cognitive processing or antipsychotic-like activity. The in vitro selectivity of
      Lu AF64280 was determined against a panel of PDE enzymes and 3',5'-cyclic
      guanosine monophosphate (cGMP) levels in the hippocampus were determined using in
      vivo microdialysis. Lu AF64280 potently inhibited hPDE2A (Ki = 20 nM), 50-fold
      above moderate inhibition of both hPDE9A (Ki = 1,000 nM) and hPDE10A (Ki = 1,800
      nM), and displayed a >250-fold selectivity over all other full-length human
      recombinant PDE family members (Ki above 5,000 nM). Lu AF64280 (20 mg/kg)
      significantly increased cGMP levels in the hippocampus (p < 0.01 versus vehicle
      treated mice), attenuated sub-chronic phencyclidine-induced deficits in novel
      object exploration in rats (10 mg/kg, p < 0.001 versus vehicle-treated), blocked
      early postnatal phencyclidine-induced deficits in the
      intradimensional/extradimensional shift task in rats (1 and 10 mg/kg, p < 0.001
      versus vehicle-treated) and attenuated spontaneous P20-N40 auditory gating
      deficits in DBA/2 mice (20 mg/kg, p < 0.05 versus vehicle-treated). In contrast,
      Lu AF64280 failed to attenuate phencyclidine-induced hyperactivity in mice, and
      was devoid of antipsychotic-like activity in the conditioned avoidance response
      paradigm in rats, at any dose tested. Lu AF64280 represents a novel tool compound
      for selective PDE2A inhibition that substantiates a critical role of this enzyme
      in cognitive processes under normal and pathological conditions.

PMID- 24577523
TI  - Spectral sharpening of color sensors: diagonal color constancy and beyond.
AB  - It has now been 20 years since the seminal work by Finlayson et al. on the use of
      spectral sharpening of sensors to achieve diagonal color constancy. Spectral
      sharpening is still used today by numerous researchers for different goals
      unrelated to the original goal of diagonal color constancy e.g., multispectral
      processing, shadow removal, location of unique hues. This paper reviews the idea
      of spectral sharpening through the lens of what is known today in color
      constancy, describes the different methods used for obtaining a set of sharpening
      sensors and presents an overview of the many different uses that have been found
      for spectral sharpening over the years. 

PMID- 24577524
TI  - Toward a new generation of photonic humidity sensors.
AB  - This review offers new perspectives on the subject and highlights an area in need
      of further research. It includes an analysis of current scientific literature
      mainly covering the last decade and examines the trends in the development of
      electronic, acoustic and optical-fiber humidity sensors over this period. The
      major findings indicate that a new generation of sensor technology based on
      optical fibers is emerging. The current trends suggest that electronic humidity
      sensors could soon be replaced by sensors that are based on photonic structures.
      Recent scientific advances are expected to allow dedicated systems to avoid the
      relatively high price of interrogation modules that is currently a major
      disadvantage of fiber-based sensors. 

PMID- 24577525
TI  - Integrating sensory/actuation systems in agricultural vehicles.
AB  - In recent years, there have been major advances in the development of new and
      more powerful perception systems for agriculture, such as computer-vision and
      global positioning systems. Due to these advances, the automation of agricultural
      tasks has received an important stimulus, especially in the area of selective
      weed control where high precision is essential for the proper use of resources
      and the implementation of more efficient treatments. Such autonomous agricultural
      systems incorporate and integrate perception systems for acquiring information
      from the environment, decision-making systems for interpreting and analyzing such
      information, and actuation systems that are responsible for performing the
      agricultural operations. These systems consist of different sensors, actuators,
      and computers that work synchronously in a specific architecture for the intended
      purpose. The main contribution of this paper is the selection, arrangement,
      integration, and synchronization of these systems to form a whole autonomous
      vehicle for agricultural applications. This type of vehicle has attracted growing
      interest, not only for researchers but also for manufacturers and farmers. The
      experimental results demonstrate the success and performance of the integrated
      system in guidance and weed control tasks in a maize field, indicating its
      utility and efficiency. The whole system is sufficiently flexible for use in
      other agricultural tasks with little effort and is another important contribution
      in the field of autonomous agricultural vehicles. 

PMID- 24577526
TI  - A textile-based wearable sensing device designed for monitoring the flexion angle
      of elbow and knee movements.
AB  - In this work a wearable gesture sensing device consisting of a textile strain
      sensor, using elastic conductive webbing, was designed for monitoring the flexion
      angle of elbow and knee movements. The elastic conductive webbing shows a linear
      response of resistance to the flexion angle. The wearable gesture sensing device
      was calibrated and then the flexion angle-resistance equation was established
      using an assembled gesture sensing apparatus with a variable resistor and a
      protractor. The proposed device successfully monitored the flexion angle during
      elbow and knee movements. 

PMID- 24577527
TI  - LBP-4a improves insulin resistance via translocation and activation of GLUT4 in
      OLETF rats.
AB  - Lycium barbarum polysaccharide (LBP) has been shown to ameliorate insulin
      resistance, but the identification of compounds from LBP and the mechanisms have
      not been clarified. In this study, LBP-4a was purified from Lycium barbarum by
      DEAE cellulose and Sephadex G-100 column chromatography, and the effects of LBP
      4a on insulin resistance were investigated. The results indicated that LBP-4a
      caused translocation of the glucose transporter isoform 4 (GLUT4) to the cell
      surface, which in turn stimulated glucose uptake, and the effect was sensitive to
      wortmannin, an inhibitor of phosphoinositol 3-kinase (PI3-K), and SB203580, an
      inhibitor of p38 mitogen activated protein kinase (p38 MAPK (alpha, beta)).
      Furthermore, the effects of LBP-4a on p38 MAPK activities were abrogated by
      pretreatment of rat adipocytes using SB203580. In summary, LBP-4a improved
      insulin resistance via translocation and activation of GLUT4 in OLETF rats, and
      the activation of PI3-K and p38 MAPK contributed to these effects.

PMID- 24577529
TI  - A semiconducting microporous framework of Cd6Ag4(SPh)16 clusters interlinked
      using rigid and conjugated bipyridines.
AB  - Ternary supertetrahedral chalcogenolate clusters were interlinked with
      bipyridines into a microporous semiconducting framework with properties
      qualitatively different from those of the original clusters. Both the framework
      and the clusters were effective photocatalysts, and rapidly degraded the dye
      rhodamine B. 

PMID- 24577528
TI  - High-throughput de novo screening of receptor agonists with an automated single
      cell analysis and isolation system.
AB  - Reconstitution of signaling pathways involving single mammalian transmembrane
      receptors has not been accomplished in yeast cells. In this study, intact EGF
      receptor (EGFR) and a cell wall-anchored form of EGF were co-expressed on the
      yeast cell surface, which led to autophosphorylation of the EGFR in an EGF
      dependent autocrine manner. After changing from EGF to a conformationally
      constrained peptide library, cells were fluorescently labeled with an anti
      phospho-EGFR antibody. Each cell was subjected to an automated single-cell
      analysis and isolation system that analyzed the fluorescent intensity of each
      cell and automatically retrieved each cell with the highest fluorescence. In ~3.2
      * 10(6) peptide library, we isolated six novel peptides with agonistic activity
      of the EGFR in human squamous carcinoma A431 cells. The combination of yeast
      cells expressing mammalian receptors, a cell wall-anchored peptide library, and
      an automated single-cell analysis and isolation system might facilitate a
      rational approach for de novo drug screening. 

PMID- 24577530
TI  - Flavaglines target primitive leukemia cells and enhance anti-leukemia drug
      activity.
AB  - Identification of agents that target human leukemia stem cells is an important
      consideration for the development of new therapies. The present study
      demonstrates that rocaglamide and silvestrol, closely related natural products
      from the flavagline class of compounds, are able to preferentially kill
      functionally defined leukemia stem cells, while sparing normal stem and
      progenitor cells. In addition to efficacy as single agents, flavaglines sensitize
      leukemia cells to several anticancer compounds, including front-line
      chemotherapeutic drugs used to treat leukemia patients. Mechanistic studies
      indicate that flavaglines strongly inhibit protein synthesis, leading to the
      reduction of short-lived antiapoptotic proteins. Notably though, treatment with
      flavaglines, alone or in combination with other drugs, yields a much stronger
      cytotoxic activity toward leukemia cells than the translational inhibitor
      temsirolimus. These results indicate that the underlying cell death mechanism of
      flavaglines is more complex than simply inhibiting general protein translation.
      Global gene expression profiling and cell biological assays identified Myc
      inhibition and the disruption of mitochondrial integrity to be features of
      flavaglines, which we propose contribute to their efficacy in targeting leukemia
      cells. Taken together, these findings indicate that rocaglamide and silvestrol
      are distinct from clinically available translational inhibitors and represent
      promising candidates for the treatment of leukemia.

PMID- 24577541
TI  - Enrollment in clinical cancer trials: how are we doing and what are the obstacles
      to improving enrollment rates? A 2-year retrospective review of pediatric cancer
      trial enrollment in New Zealand.
AB  - Clinical trials contribute to the establishment of the best therapy for children
      with cancer. This study looks at rates of enrollment in therapeutic clinical
      trials over a 2-year period in New Zealand and examines the reasons for
      nonenrollment. All new diagnoses of cancer in children aged 16 or younger over
      the period of 1 January, 2009 to 31 December, 2010 were identified through the
      New Zealand Child Cancer Registry. Clinical trial enrollment status was
      identified from the medical records. For those not enrolled, the reason for
      nonenrollment was ascertained. A total of 28% of children diagnosed with cancer
      who received chemotherapy with curative intent in this time period were enrolled
      on clinical trials. The 2 most common reasons for nonenrollment in this study
      were that no study was open locally in which to enroll children (27%) or that
      previously open-clinical trials were closed to accrual at the time of the child's
      diagnosis (20%). In New Zealand, enrollment rates on clinical trials for children
      with cancer are lower than expected. 

PMID- 24577542
TI  - An adolescent with a rare midline neck tumor: thyroid carcinoma in a thyroglossal
      duct cyst.
AB  - Occurrence of malignancy in a thyroglossal duct cyst (TDC) in children and
      adolescents is very rare, preoperative diagnosis is a challenge, and appropriate
      management is still debated. We report a 19-year-old male patient referred for a
      midline neck mass diagnosed as an atypical TDC after initial and subsequent
      investigations. Ultrasound-guided fine-needle aspiration (FNA) of the mass was
      diagnostic for papillary thyroid carcinoma. Sistrunk procedure and total
      thyroidectomy were performed. Histologic analysis confirmed the presence of
      papillary thyroid carcinoma within TDC, infiltrating surrounding soft tissues.
      Postoperatively, radioiodine ablation treatment was administered, followed by TSH
      suppression therapy. 

PMID- 24577531
TI  - Comparative analysis of FoxP3(+) regulatory T cells in the target tissues and
      blood in chronic graft versus host disease.
AB  - Activation and migration of regulatory T cells (Treg) into tissue is critical in
      control of inflammation, but has not been examined extensively in chronic graft
      versus host disease (cGVHD). In parallel studies of tissues and blood, we
      determined that FoxP3(+) T cells increased in proportion to T effectors (Teff) in
      tissue infiltrates in oral and cutaneous lichenoid cGVHD. These FoxP3(+) cells
      expressed distinguishing phenotypic and functional markers of Treg (CD3(+),
      CD4(+), CD27(+), ICOS(+) and CD39(+)), not found on FoxP3(-) Teff. Both Teff and
      FoxP3(+) Treg expressed T-bet and the chemokine receptor CXCR3, however,
      consistent with a common mechanism of chemokine-mediated migration into tissue.
      Furthermore, functional markers (ICOS and CD39) and chemokine receptors (CXCR3)
      were both present in a higher proportion of FoxP3(+) cells in tissues than in
      peripheral blood, consistent with recruitment and activation of Treg in cGVHD
      target tissues. Finally, the 'activated' CD45RA(-)FoxP3(hi) subset of Treg cells,
      which highly express functional markers, were found in comparable frequencies in
      cGVHD patients and normal controls, despite a significant deficit in naive
      'resting' Treg. These findings are consistent with Treg capacity to upregulate
      functional markers and traffick into tissue in cGVHD.

PMID- 24577532
TI  - How we manage follicular lymphoma.
AB  - Major changes have taken place within the last few years in the management of
      follicular lymphoma (FL) leading to substantial improvement in prognosis and
      overall survival. For some patients with limited disease stages I and II,
      radiotherapy may be associated with durable responses; however, it is unclear
      whether patients are cured and new approaches such as the combination of
      irradiation with rituximab or even single-agent rituximab need to be explored.
      Whereas watch and wait is the current standard for stage III and IV disease with
      low tumour burden, better indices are warranted to potentially select patients
      for whom early intervention is preferred. For advanced stages with a high tumour
      burden, immunochemotherapy followed by 2 years of rituximab maintenance is widely
      accepted as standard therapy, although re-treatment at recurrence may be an
      alternative option. Highly attractive new therapeutic options have recently
      arisen from new antibodies, and from new agents targeting oncogenic pathways such
      as B-cell receptor signalling pathways or inhibition of bcl 2. Furthermore,
      immunomodulatory drugs may add to the therapeutic armamentarium and may lead to
      'chemotherapy-free' therapies in the near future. Hence, the management of FLs
      has become a moving target and the hope is justified that the long-term
      perspectives of patients suffering from the disease will be further improved in
      the near future. 

PMID- 24577543
TI  - Novel t(2;12)(q31;p13) in a case of pediatric T-cell acute lymphoblastic
      leukemia.
AB  - BACKGROUND: The role of ETV6 in B-cell acute lymphoblastic leukemia (ALL) has
      been extensively studied, whereas only rare cases of ETV6 involvement in
      pediatric T-cell ALL have been described. OBSERVATION: We report a case of T-cell
      ALL in a 13-year-old boy with t(2;12)(q31;p13) involving ETV6, resulting in the
      relocation of the ETV6 from 12p13 to 2q31 locus that harbors the class 1 homeobox
      gene (HOX) cluster D, which is expressed during the early stages of T-cell
      development. CONCLUSIONS: We report a novel translocation in T-cell ALL
      highlighting the involvement of ETV6 and potentially the HOXD gene cluster in a
      case of T-cell ALL.

PMID- 24577545
TI  - Splenectomy for Children With Thalassemia: Total or Partial Splenectomy, Open or
      Laparoscopic Splenectomy.
AB  - Splenomegaly and hypersplenism are common complications among children with
      thalassemia necessitating splenectomy. Thirty-six children (27 beta-thalassemia
      major, 3 Hb H disease, and 6 thalassemia intermediate) had total splenectomy (11
      laparoscopic and 13 open splenectomy) or partial splenectomy (12 patients). In
      the partial splenectomy group, 2 with Hb H required no transfusions. For those
      with beta-thalassemia major who had partial splenectomy (9 patients), there was a
      reduction in the number of transfusions from a preoperative mean of 15.2
      transfusions per year to a postoperative mean of 8.2 transfusions per year.
      Subsequently and as a result of increase in the size of splenic remnant, their
      transfusions increased, but none required total splenectomy. Twenty-four patients
      had total splenectomy (13 open and 11 laparoscopic splenectomy). Their
      postsplenectomy transfusions decreased from a preoperative mean of 17.8
      transfusions per year to a postoperative mean of 10 transfusions per year. There
      was no mortality, and none developed postoperative sepsis or thrombotic
      complications. Total splenectomy is beneficial for children with beta-thalassemia
      major and hypersplenism by reducing their transfusion requirements. Laparoscopic
      splenectomy is however more beneficial. Partial splenectomy reduces their
      transfusion requirements, but only as a temporary measure, and so it is
      recommended for children younger than 5 years of age. 

PMID- 24577544
TI  - Endothelial health in childhood acute lymphoid leukemia survivors: pilot
      evaluation with peripheral artery tonometry.
AB  - BACKGROUND: Childhood cancer survivors are a growing population at risk for poor
      cardiac outcomes. Acute lymphoid leukemia (ALL) survivors are among those at
      increased risk of cardiovascular complications. Early identification of impaired
      vascular health may allow for interventions to improve these outcomes. The
      purpose of this study was to evaluate vascular health using peripheral artery
      tonometry in ALL survivors and compare results with healthy siblings. PROCEDURE:
      Sixteen ALL survivor, healthy sibling pairs, aged 8 to 20 years, were evaluated
      for vascular health and cardiovascular risk factors (body mass index, central
      adiposity, blood pressure, and fitness). One-tailed paired t test was used to
      compare the groups. RESULTS: Survivors were similar to siblings in cardiovascular
      risk measures but had poorer vascular health as measured by reactive hyperemia
      index (survivor RHI 1.54 vs. sibling 1.77; P=0.0474). CONCLUSION: This study
      reveals that even among survivors who are comparable to their healthy siblings in
      other traditional cardiovascular risks, there is evidence of poorer vascular
      health.

PMID- 24577546
TI  - Shared decision making in the management of children with newly diagnosed immune
      thrombocytopenia.
AB  - This study aimed to examine the treatment decision-making process for children
      hospitalized with newly diagnosed immune thrombocytopenia (ITP). Using focus
      groups, we studied children with ITP, parents of children with ITP, and health
      care professionals, inquiring about participants' experience with decision
      support and decision making in newly diagnosed ITP. Data were examined using
      thematic analysis. Themes that emerged from children were feelings of "anxiety,
      fear, and confusion"; the need to "understand information"; and "treatment
      choice," the experience of which was age dependent. For parents, "anxiety, fear,
      and confusion" was a dominant theme; "treatment choice" revealed that
      participants felt directed toward intravenous immune globulin (IVIG) for initial
      treatment. For health care professionals, "comfort level" highlighted factors
      contributing to professionals' comfort with offering options; "assumptions" were
      made about parental desire for participation in shared decision making (SDM) and
      parental acceptance of treatment options; "providing information" was informative
      regarding modes of facilitating SDM; and "treatment choice" revealed a
      discrepancy between current practice (directed toward IVIG) and the ideal of SDM.
      At our center, families of children with newly diagnosed ITP are not experiencing
      SDM. Our findings support the implementation of SDM to facilitate patient
      centered care for the management of pediatric ITP. 

PMID- 24577547
TI  - Acute hemolytic anemia as an initial presentation of Wilson disease in children.
AB  - BACKGROUND: Wilson disease (WD) is an inherited disorder of copper metabolism.
      Hemolytic anemia in WD occurs in up to 17% of patients at some point during their
      illness. AIM: To screen for WD among children presenting with hemolytic anemia.
      METHODOLOGY: Twenty cases (mean age, 8.8 +/- 3.9 y) with Coombs-negative
      hemolytic anemia, attending the hematology clinic of children hospital, Cairo
      University, were screened for WD by serum ceruloplasmin level, 24 hours urinary
      copper before and after D-penicillamine challenge test, and slit-lamp examination
      for detecting Kayser-Fleischer rings. RESULTS: No case had low ceruloplasmin,
      whereas bilateral Kayser-Fleischer rings was detected in 5% of our cases. Urinary
      copper was elevated in 5% before and in 40% after D-penicillamine challenge test.
      According to the scoring system used, 1 case had definite WD and 7 cases were
      likely to have WD. These 8 (40%) cases were referred to as group B. Group B had a
      significantly lower hemoglobin, mean corpuscular volume, mean corpuscular
      hemoglobin, and reticulocytes (P=0.04, 0.001, 0.04, and 0.04, respectively) and a
      significantly higher urinary copper after penicillamine (P=0.000) when compared
      with group A (unlikely WD). CONCLUSION: WD is not uncommon in children with
      hemolytic anemia after exclusion of other common causes.

PMID- 24577548
TI  - DNA Repair Gene Polymorphisms and Their Relation With DNA Damage, DNA Repair, and
      Total Antioxidant Capacity in Childhood Acute Lymphoblastic Leukemia Survivors.
AB  - Oxidative stress and defective DNA repair are major contributory factors in the
      initiation and progression of carcinogenesis. Chemotherapy and radiotherapy cause
      oxidative DNA damage, consume antioxidant capacity, and impair DNA repair
      activity. These effects of chemotherapy and radiotherapy may be contributory
      factors in the development of secondary malignancy in cancer survivors. Basal,
      H2O2-induced, and postrepair DNA damage; urinary 8-hydroxydeoxyguanosine level as
      a marker of oxidatively damaged DNA; and serum total antioxidant capacity were
      measured; XPD Lys751Gln, XRCC1 Arg399Gln, and XRCC1 Arg194Trp polymorphisms were
      analyzed in childhood acute lymphoblastic leukemia (ALL) survivors. Basal and
      H2O2-induced DNA damage were found to be higher in the ALL survivor group versus
      the control group, however, there was no significant difference between the other
      parameters. No association was found between the examined parameters and
      polymorphisms of XPD 751 and XRCC1 399 and both the groups. XRCC1 194Trp allele
      was found to be associated with a low level of postrepair DNA damage in the ALL
      survivors. In conclusion, basal DNA damage and susceptibility to oxidation are
      high in childhood ALL survivors. This situation which may easily lead to
      occurrence of a secondary cancer does not seem to be a result of deficient DNA
      repair. 

PMID- 24577550
TI  - An unusual case of Ewing sarcoma: a middle-aged woman with multiple recurrences
      over 36 years.
AB  - Ewing sarcoma (EWS) is a primary bone tumor that most often occurs in the long
      bones of young patients. EWS is typically an aggressive tumor that is highly
      sensitive to radiation therapy; recurrences often occur, usually within a year of
      treatment. We present a case of EWS that first presented in a patient at the age
      of 40 with extraosseous disease. The patient was treated initially with radiation
      and surgery. Over the following 36-year period, the tumor recurred once and
      metastasized twice. The morphologic, immunohistochemical, and cytogenetic
      features of this tumor were typical of EWS, and the tumor was highly responsive
      to radiation therapy. The unusually prolonged course in this patient demonstrates
      significant heterogeneity in the biological behavior of EWS, and the importance
      of randomized trials in cancer therapy. 

PMID- 24577549
TI  - Recent advances in understanding the etiology and pathogenesis of pediatric germ
      cell tumors.
AB  - Pediatric germ cell tumors (GCTs) are rare neoplasms arising predominantly in the
      gonads and sacrococcygeal, mediastinal, and intracranial localizations. In this
      article, we review current knowledge of pathogenesis of pediatric GCTs, which
      differs from adult/adolescent GCTs. One distinctive feature is the absence of a
      progenitor stage, such as carcinoma in situ or gonadoblastoma, which are seen in
      adult/adolescent GCTs, except spermatocytic seminoma. The primordial germ cell
      (PGC) is the suggested origin of all GCTs, with variations in histology
      reflecting differentiation stage. Expression of pluripotency transcription
      factors OCT-3/4, NANOG, and AP-2gamma in germinomas/seminomas/dysgerminomas is
      consistent with retaining a germ cell phenotype. Teratomas, in contrast, develop
      through a pathway of aberrant somatic differentiation of immature germ cells, and
      the yolk sac tumors and choriocarcinomas result from abnormal extraembryonic
      differentiation. In pediatric GCTs, origin is suggested at an earlier
      developmental stage because of predisposing genetic factors, although responsible
      genes remain largely unknown. Some extragonadal GCTs have been linked to
      overexpression of the KIT/KITLG system, allowing for survival of aberrantly
      migrated ectopic PGCs. Infant gonadal/sacrococcygeal GCTs may be caused by
      apoptosis-related pathways, consistent with an association with polymorphisms in
      BAK1. Although recent advances have identified candidate pathways, further effort
      is needed to answer central questions of pathogenesis of these fascinating
      tumors.

PMID- 24577552
TI  - Treatment of hepatoblastoma with high-dose chemotherapy and stem cell rescue: the
      pediatric blood and marrow transplant consortium experience and review of the
      literature.
AB  - BACKGROUND: Children with high-risk or relapsed hepatoblastoma continue to
      represent treatment challenges. Multiple case reports have documented the use of
      high-dose chemotherapy with stem cell rescue (HDC) for this population; however,
      the efficacy and appropriate use of HDC remains unclear. PROCEDURE: A literature
      search was performed to identify cases of hepatoblastoma that were treated with
      HDC. Additional patients were identified by a query through the Pediatric Blood
      and Marrow Transplant Consortium. All cases were categorized as undergoing HDC as
      part of their initial treatment or for relapsed disease. Overall survival (OS)
      and event-free survival (EFS) proportions were calculated for each group.
      Subgroup analyses were performed looking at the effects of remission status,
      initial stage, and relapse site. RESULTS: Forty-two patients were identified.
      Thirty-one patients received HDC as part of their initial treatment and 55% were
      long-term survivors with 48% event-free. Eleven received HDC for relapsed disease
      and 64% were long-term survivors, 36% without events. CONCLUSIONS: It is
      difficult to draw firm conclusions from a small number of nonrandomized patients
      who had different stages, treatments, and events before undergoing HDC. However,
      our calculated EFS and OS proportions are consistent with current data using
      multimodal therapy without HDC, suggesting that HDC (at least as currently
      delivered) for hepatoblastoma may not be beneficial.

PMID- 24577551
TI  - Pathologic risk-based adjuvant chemotherapy for unilateral retinoblastoma
      following enucleation.
AB  - BACKGROUND: There are no standardized diagnostic or treatment guidelines for
      patients with advanced unilateral retinoblastoma. MATERIALS AND METHODS: Patients
      with advanced unilateral retinoblastoma were prospectively treated after
      enucleation using a risk-based protocol. Patients were assigned to low risk (LR),
      intermediate risk (IR), or high risk (HR) based on pathology. LR patients
      underwent observation. IR patients received 4 courses of chemotherapy with
      vincristine, doxorubicin, and cyclophosphamide (VDC). In the HR group, patients
      received 3 courses of VDC alternating with 3 courses of vincristine, carboplatin,
      and etoposide (VCE) and irradiation when indicated. RESULTS: Fifty patients with
      advanced unilateral retinoblastoma were treated (LR, n=36; IR, n=7; HR, n=7). All
      eyes were Reese-Ellsworth group V. All bone scans (n=81), lumbar punctures
      (n=16), and bone marrow aspirates (n=16) were negative. Chemotherapy was well
      tolerated. Grades 3/4 hematologic toxicities were seen in all patients; grades
      3/4 nonhematologic toxicities were seen in half the patients. Only one patient in
      the HR group received radiation therapy. All patients were alive at the time of
      analysis with no signs of disease recurrence. Median follow-up was 3.4 years
      (range, 0.8 to 6.4 y). CONCLUSIONS: Patients with nonmetastatic unilateral
      retinoblastoma undergoing primary enucleation can be cured with a graduated
      intensity approach based on pathology.

PMID- 24577553
TI  - Advanced sclerosis of the chest wall skin secondary to chronic graft-versus-host
      disease: a case with severe restrictive lung defect.
AB  - Pulmonary chronic graft-versus-host disease (cGvHD) is one of the most common
      causes of morbidity and mortality after allogeneic hematopoietic stem cell
      transplantation (aHSCT). Herein, we describe a patient with severe restrictive
      lung defect secondary to cGvHD. A 21-year-old male patient was admitted to our
      pediatric intensive care unit (PICU) with pneumonia and respiratory distress. He
      had a history of aHSCT for chronic myelogeneous leukemia at the age of 17 years.
      Six months after undergoing aHSCT, he had developed cGvHD involving skin, mouth,
      eye, lung, liver, and gastrointestinal tract. At the time of PICU admission he
      had respiratory distress and required ventilation support. Thorax high-resolution
      computed tomography was consistent with bronchiolitis obliterans. Although
      bronchiolitis obliterans is an obstructive lung defect, a restrictive pattern
      became prominent in the clinical course because of the sclerotic chest wall skin.
      The activity of cGvHD kept increasing despite the therapy and we lost the patient
      because of severe respiratory distress and massive hemoptysis secondary to
      bronchiectasis. In conclusion, pulmonary cGvHD can present with restrictive
      changes related with the advanced sclerosis of the chest wall skin. Performing a
      fasciotomy or a scar revision for the rigid chest wall in selected patients may
      improve the patients ventilation. 

PMID- 24577554
TI  - Inadequate folinic acid rescue after methotrexate causing neurocognitive and
      neuroradiological central nervous system late effects in children with acute
      lymphatic leukemia.

PMID- 24577555
TI  - The influence of body weight on the prevalence and severity of hidradenitis
      suppurativa.
AB  - The prevalence of hidradenitis suppurativa (HS) has been estimated to be 1% of
      the population. Obesity is considered a co-morbidity, but the prevalence of HS in
      obese population is not known. A retrospective questionnaire was distributed to
      383 patients over 2 years after bariatric surgery. Data on pre- and post-surgery
      HS symptoms and disease severity were studied. Disease severity was assessed by
      number of involved sites. General skin problems rated numerically on an anchored
      1-10 scale. Valid responses were obtained from 249/383 (65%). A point prevalence
      of 18.1% (45/249) HS was found. The number of patients reporting HS symptoms
      after weight loss decreased by 35% and the mean number of involved sites was
      reduced from 1.93 to 1.22 following weight loss (p = 0.003). The prevalence of HS
      appears higher in the obese than in the background population, and a weight loss
      of more than 15% is associated with a significant reduction of disease severity. 

PMID- 24577557
TI  - PdCl2 catalyzed efficient assembly of organic azides, CO, and alcohols under mild
      conditions: a direct approach to synthesize carbamates.
AB  - A simple and readily available PdCl2 catalyzed carbamate synthesis method via
      isocyanate generation and application in situ has been developed. This chemistry
      provides an efficient and practical approach to synthesize carbamates from simple
      organic azides, CO atmosphere and alcohols. The broad scope, mild and neutral
      conditions, and only N2 as the byproduct make this transformation very useful.
      Moreover, simple examples of modification of bioactive molecules and construction
      of macrocycles were achieved through this protocol. 

PMID- 24577556
TI  - Encapsulation of sodium radio-iodide in fullerene C60.
AB  - In this work we have studied the well-known "Buckminsterfullerene" C60 containing
      different amounts, from one to four molecules, of sodium radio-iodide (Na(131)I),
      with density functional theory geometrical optimizations and molecular dynamics
      at 310 K and atmospheric pressure. We found that nanocapsules with the
      radioactive content Na131I@C60, 2Na131I@C60 and 3Na131I@C60 are stable.
      Furthermore, the C60 fullerene undergoes expansion when the number of sodium
      radio-iodide molecules inside increases. Utilizing the Mulliken charge
      distribution analysis it was shown that a small charge transfer occurs from
      iodine to fullerene's carbon atoms. This produces repulsion which increases bond
      lengths thus the structure is weakened while the binding energy per atom
      decreases. For the case in which the fullerene initially contains four sodium
      radio-iodide molecules the expansion is greater than that which the structure can
      withstand. So the fullerene breaks and releases its contents. This result leads
      us to conclude that the fullerene can encapsulate up to three molecules of sodium
      radio-iodide.

PMID- 24577558
TI  - On the calculation of the Israeli risk adjustment rates.
AB  - OBJECTIVE: The Israeli risk adjustment formula, introduced in 1995 and which
      serves for the allocation of the health budget to the sickness funds, is unique
      compared to countries with a similar national health insurance system in that it
      is not calculated on the basis of actual cost data of the sickness funds but on
      the basis of quantities retrieved from surveys. The current article aims to
      analyze the implications of the Israeli methodology. METHODS: The article
      examines the validity of the Israeli methodology used to set the 2004 risk
      adjustment rates and compare these rates with the "correct" ones, which are
      derived from the 2004 internal relative cost scales of the sickness funds.
      RESULTS: The Israeli methodology ignores services provided by the sickness funds
      and assumes constant unit cost across the sickness funds, an assumption which is
      implausible. Comparing the actual and the "correct" rates, it turns out that the
      actual rates over-compensate all the sickness funds for members in age 0-14, and
      under-compensate them for insurees aged 55+. In age 0-4, the over-compensation
      per capita is about NIS 1,500 while the under-compensation in age group 75+
      reaches NIS 1,600. CONCLUSIONS: The current risk adjustment formula distorts the
      intended competition on good quality care among the sickness funds, and turns it
      into a competition on profitable members. After 18 years of using incorrect
      rates, the Israeli risk adjustment rates should be calculated, as is common in
      other systems, based on individual cost data from the sickness funds.

PMID- 24577562
TI  - Down- and up-conversion luminescent carbon dot fluid: inkjet printing and gel
      glass fabrication.
AB  - Room temperature liquid-like nanoparticles have emerged as an exciting new
      research and development area, because their properties could be tailored over a
      broad range by manipulating geometric and chemical characteristics of the
      inorganic core and organic canopy. However, related applications are rarely
      reported due to the multi-step synthesis process and potential toxicity of
      cadmium based nanomaterials. In this study, we prepared inexpensive and eco
      friendly carbon dot fluid by the direct thermal decomposition method. The carbon
      dot fluid can be excited from UV to near infrared light, and can be prepared as
      highly concentrated luminescent ink or incorporated into sol-gel derived
      organically modified silicate glass, suggesting that it has great application
      potential in the field of printable electronics, solid state lighting and so on. 

PMID- 24577561
TI  - Cognitive lifestyle jointly predicts longitudinal cognitive decline and mortality
      risk.
AB  - Cognitive lifestyle measures such as education, occupation, and social engagement
      are commonly associated with late-life cognitive ability although their
      associations with cognitive decline tend to be mixed. However, longitudinal
      analyses of cognition rarely account for death and dropout, measurement error of
      the cognitive phenotype, and differing trajectories for different population sub
      groups. This paper applies a joint latent class mixed model (and a multi-state
      model in a sensitivity analysis) that accounts for these issues to a large (n =
      3,653), population-based cohort, Paquid, to model the relationship between
      cognitive lifestyle and cognitive decline. Cognition was assessed over a 20-year
      period using the Mini-Mental State Examination. Three cognitive lifestyle
      variables were assessed: education, mid-life occupation, and late-life social
      engagement. The analysis identified four latent sub-populations with class
      specific longitudinal cognitive decline and mortality risk. Irrespective of the
      cognitive trajectory, increased social engagement was associated with a decreased
      mortality risk. High education was associated with the most favourable cognitive
      trajectory, and after adjusting for cognitive decline, with an increased
      mortality risk. Mid-life occupational complexity was also associated with more
      favourable trajectories but not with mortality risk. To realistically examine the
      link between cognitive lifestyle and cognitive decline, complex statistical
      models are required. This paper applies and compares in a sensitivity analysis
      two such models, and shows education to be linked to a compression of cognitive
      morbidity irrespective of cognitive trajectory. Furthermore, a potentially
      modifiable variable, late-life social engagement is associated with a decreased
      mortality risk in all of the population sub-groups. 

PMID- 24577563
TI  - Order and execution of DVT prophylaxis: "the best-laid plans of mice and men".

PMID- 24577566
TI  - The impact of dose/time modification in irinotecan- and oxaliplatin-based
      chemotherapies on outcomes in metastatic colorectal cancer.
AB  - PURPOSE: This study was designed to evaluate (1) the impact of relative dose
      intensity (RDI) on tumor response and survival outcomes and (2) the influence of
      dose reduction and schedule modification on outcomes in patients with metastatic
      colorectal cancer (mCRC). METHODS: Pooled datasets from two previous phase II
      trials of FOLFIRI (CCOG-0502; n = 36) and mFOLFOX6 (CCOG-0704; n = 30) in
      patients with mCRC were analyzed retrospectively. The RDIs of irinotecan and
      oxaliplatin were compared to response rate (RR), disease control rate (DCR),
      progression-free survival (PFS) and overall survival (OS). To assess the effects
      of dose reduction and schedule modification, the effects of dose index (DI) and
      time index (TI) on outcomes were evaluated. RESULTS: The median RDIs of
      irinotecan in FOLFIRI and oxaliplatin in mFOLFOX6 were 80 and 79 %, respectively.
      Higher RDI of irinotecan in FOLFIRI was associated with significant improvements
      in RR (65 vs. 6 %, p < 0.01), DCR (100 vs. 59 %, p < 0.01), PFS (9.9 vs. 5.6
      months, p < 0.01) and OS (26.7 vs. 12.9 months, p = 0.01) and was the only
      independent factor associated with PFS [hazard ratio (HR) 8.48, p < 0.01). Higher
      RDI of oxaliplatin in FOLFOX was significantly associated with DCR (65 vs. 6 %, p
      < 0.01), and higher TI of oxaliplatin was the only independent factor associated
      with PFS (HR 2.74, p = 0.04). CONCLUSION: RDIs of irinotecan and oxaliplatin
      affected clinical outcomes. Dose reductions in irinotecan, as indicated by DI,
      and time delays in oxaliplatin, as indicated by TI, were the only independent
      prognostic factors predicting PFS in patients receiving FOLFIRI and FOLFOX6,
      respectively.

PMID- 24577567
TI  - Semiparametric methods for center effect measures based on the ratio of survival
      functions.
AB  - The survival function is often of chief interest in epidemiologic studies of time
      to an event. We develop methods for evaluating center-specific survival outcomes
      through a ratio of survival functions. The proposed method assumes a center
      stratified additive hazards model, which provides a convenient framework for our
      purposes. Under the proposed methods, the center effects measure is cast as the
      ratio of subject-specific survival functions under two scenarios: the scenario in
      which the subject is treated at center [Formula: see text]; and that wherein the
      subject is treated at a hypothetical center with survival function equal to the
      population average. The proposed measure reduces to the ratio of baseline
      survival functions, but is invariant to the choice of baseline covariate level.
      We derive the asymptotic properties of the proposed estimators, and assess finite
      sample characteristics through simulation. The proposed methods are applied to
      national kidney transplant data. 

PMID- 24577564
TI  - Laterality defects other than situs inversus totalis in primary ciliary
      dyskinesia: insights into situs ambiguus and heterotaxy.
AB  - BACKGROUND: Motile cilia dysfunction causes primary ciliary dyskinesia (PCD),
      situs inversus totalis (SI), and a spectrum of laterality defects, yet the
      prevalence of laterality defects other than SI in PCD has not been prospectively
      studied. METHODS: In this prospective study, participants with suspected PCD were
      referred to our multisite consortium. We measured nasal nitric oxide (nNO) level,
      examined cilia with electron microscopy, and analyzed PCD-causing gene mutations.
      Situs was classified as (1) situs solitus (SS), (2) SI, or (3) situs ambiguus
      (SA), including heterotaxy. Participants with hallmark electron microscopic
      defects, biallelic gene mutations, or both were considered to have classic PCD.
      RESULTS: Of 767 participants (median age, 8.1 years, range, 0.1-58 years),
      classic PCD was defined in 305, including 143 (46.9%), 125 (41.0%), and 37
      (12.1%) with SS, SI, and SA, respectively. A spectrum of laterality defects was
      identified with classic PCD, including 2.6% and 2.3% with SA plus complex or
      simple cardiac defects, respectively; 4.6% with SA but no cardiac defect; and
      2.6% with an isolated possible laterality defect. Participants with SA and
      classic PCD had a higher prevalence of PCD-associated respiratory symptoms vs SA
      control participants (year-round wet cough, P < .001; year-round nasal
      congestion, P = .015; neonatal respiratory distress, P = .009; digital clubbing,
      P = .021) and lower nNO levels (median, 12 nL/min vs 252 nL/min; P < .001).
      CONCLUSIONS: At least 12.1% of patients with classic PCD have SA and laterality
      defects ranging from classic heterotaxy to subtle laterality defects. Specific
      clinical features of PCD and low nNO levels help to identify PCD in patients with
      laterality defects. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00323167; URL:
      www.clinicaltrials.gov.

PMID- 24577569
TI  - The development of giant phagocytes in long-term neutrophil cultures.
AB  - We tested the hypothesis that in long-term culture conditions, some neutrophils
      remain viable and participate in debris clearance, and autophagy is involved in
      their prolonged survival. Neutrophils, classified as professional phagocytes,
      have the shortest half-life among leukocytes and are constitutively committed to
      apoptosis. Apoptotic neutrophils are actively removed by Mphi/DCs. However, early
      and acute inflammatory infiltrates primarily consist of neutrophils. Recently,
      neutrophils were suggested to facilitate debris clearance at inflammatory sites
      when the Mphi/DC system is insufficient. Here, purified CD15(+)/CD66b(+)/CD63(+)
      neutrophils were followed up to 7 days in culture using light, time-lapse, and
      confocal microscopy. After 3 days in culture, Annexin-V(-)/LC3B(+) large
      vacuolated cells, engulfing cellular residues, were noted among apoptotic
      neutrophils and cell debris. Thereafter, these cells were vastly enlarged and
      exhibited a neutrophilic phenotype (CD15(+)/CD63(+)/MPO(+)/CD66b(+)),
      phagocytosis, and oxidative burst activity. They also expressed CD68 scavenger
      receptors and internalized oxLDL. But, unlike in fresh neutrophils or cultured
      monocytes, oxLDL treatment increased their ROS production. Additionally, these
      phagocytes contained LC3B-coated vacuoles and LC3B aggregates, indicating the
      activation of autophagy. An intensive LC3B accumulation was also noted during
      oxLDL internalization. Importantly, the inhibition of autophagy by 3-MA or BafA1
      prevented their development. In conclusion, the internalization of neutrophil
      remnants may induce activation of autophagic mechanisms in some neutrophil
      subsets or precursors. This may lead to cell adaptation and survival, resulting
      in their transformation into long-lived Gphi and potentially suggesting their
      involvement in inflammatory/anti-inflammatory processes. 

PMID- 24577568
TI  - HIV infection of macrophages is enhanced in the presence of increased expression
      of CD163 induced by substance P.
AB  - Activation of NK1R by SP contributes to increased HIV-1 infection in macrophages.
      The scavenger receptor CD163 is expressed on cells of monocyte-macrophage origin.
      Our main goal was to determine if there is interplay among SP, CD163 expression,
      and HIV infection in macrophages. We showed that SP triggers intracellular
      calcium elevation and increased CD163 expression in human monocytes in a time-
      and concentration-dependent manner. The role of CD163 on HIV infection was
      examined by RT-PCR in sorted monocytes (CD163(low) and CD163(high)) and in
      macrophages having CD163 knocked down using siRNA. We found that the productivity
      of HIV infection was higher in CD163(high) cells. Additionally, in macrophages
      with CD163 expression knocked down, we found a significant decrease of HIV
      infection. Furthermore, Hb-Hp complexes, which function as an endogenous ligand
      for CD163, decreased HIV infection in macrophages in a dose-dependent manner.
      Thus, we demonstrate that SP induces higher levels of CD163 in monocytes and that
      high expression of CD163 is associated with increases HIV infection in
      macrophages. Thus, in addition to being a prognostic marker of HIV infection, the
      expression of CD163 on macrophages may be critical in HIV immunopathogenesis. 

PMID- 24577570
TI  - Using a silver-enhanced microarray sandwich structure to improve SERS sensitivity
      for protein detection.
AB  - A simple and sensitive method, based on surface-enhanced Raman scattering (SERS),
      for immunoassay and label-free protein detection is reported. A series of bowl
      shaped silver cavity arrays were fabricated by electrodeposition using a self
      assembled polystyrene spheres template. The reflection spectra of these cavity
      arrays were recorded as a function of film thickness, and then correlated with
      SERS enhancement using sodium thiophenolate as the probe molecule. The results
      reveal that SERS enhancement can be maximized when the frequency of both the
      incident laser and the Raman scattering approach the frequency of the localized
      surface plasmon resonance. The optimized array was then used as the bottom layer
      of a silver nanoparticle-protein-bowl-shaped silver cavity array sandwich. The
      second layer of silver was introduced by the interactions between the proteins in
      the middle layer of the sandwich architecture and silver nanoparticles. Human IgG
      bound to the surface of this microcavity array can retain its recognition
      function. With the Raman reporter molecules labeled on the antibody, a detection
      limit down to 0.1 ng mL(-1) for human IgG is easily achieved. Furthermore, the
      SERS spectra of label-free proteins (catalase, cytochrome C, avidin and lysozyme)
      from the assembled sandwich have excellent reproducibility and high quality. The
      results reveal that the proposed approach has potential for use in qualitative
      and quantitative detection of biomolecules. 

PMID- 24577573
TI  - Measuring the electron affinity of organic solids: an indispensable new tool for
      organic electronics.
AB  - Electron affinity is a fundamental energy parameter of materials. In organic
      semiconductors, the electron affinity is closely related to electron conduction.
      It is not only important to understand fundamental electronic processes in
      organic solids, but it is also indispensable for research and development of
      organic semiconductor devices such as organic light-emitting diodes and organic
      photovoltaic cells. However, there has been no experimental technique for
      examining the electron affinity of organic materials that meets the requirements
      of such research. Recently, a new method, called low-energy inverse-photoemission
      spectroscopy, has been developed. A beam of low-energy electrons is focused onto
      the sample surface, and photons emitted owing to the radiative transition to
      unoccupied states are then detected. From the onset of the spectral intensity,
      the electron affinity is determined within an uncertainty of 0.1 eV. Unlike in
      conventional inverse-photoemission spectroscopy, sample damage is negligible and
      the resolution is improved by a factor of 2. The principle of the method and
      several applications are reported.

PMID- 24577572
TI  - Multiplex detection of disease biomarkers using SERS molecular sentinel-on-chip.
AB  - Developing techniques for multiplex detection of disease biomarkers is important
      for clinical diagnosis. In this work, we have demonstrated for the first time the
      feasibility of multiplex detection of genetic disease biomarkers using the
      surface-enhanced Raman scattering (SERS)-based molecular sentinel-on-chip (MSC)
      diagnostic technology. The molecular sentinel (MS) sensing mechanism is based
      upon the decrease of SERS intensity when Raman labels tagged at 3'-ends of MS
      nanoprobes are physically displaced from the nanowave chip's surface upon DNA
      hybridization. The use of bimetallic layer (silver and gold) for the nanowave
      fabrication was investigated. SERS measurements were performed immediately
      following a single hybridization reaction between the target single-stranded DNA
      sequences and the complementary MS nanoprobes immobilized on the nanowave chip
      without requiring target labeling (i.e., label-free), secondary hybridization, or
      post-hybridization washing, thus shortening the assay time and reducing cost. Two
      nucleic acid transcripts, interferon alpha-inducible protein 27 and interferon
      induced protein 44-like, are used as model systems for the multiplex detection
      concept demonstration. These two genes are well known for their critical role in
      host immune response to viral infection and can be used as molecular signature
      for viral infection diagnosis. The results indicate the potential of the MSC
      technology for nucleic acid biomarker multiplex detection. 

PMID- 24577574
TI  - Chemosensors and chemoreception.

PMID- 24577571
TI  - Oligonucleotide microarray chip for the quantification of MS2, PhiX174, and
      adenoviruses on the multiplex analysis platform MCR 3.
AB  - Pathogenic viruses are emerging contaminants in water which should be analyzed
      for water safety to preserve public health. A strategy was developed to quantify
      RNA and DNA viruses in parallel on chemiluminescence flow-through oligonucleotide
      microarrays. In order to show the proof of principle, bacteriophage MS2, PhiX174,
      and the human pathogenic adenovirus type 2 (hAdV2) were analyzed in spiked tap
      water samples on the analysis platform MCR 3. The chemiluminescence microarray
      imaging unit was equipped with a Peltier heater for a controlled heating of the
      flow cell. The efficiency and selectivity of DNA hybridization could be increased
      resulting in higher signal intensities and lower cross-reactivities of polymerase
      chain reaction (PCR) products from other viruses. The total analysis time for
      DNA/RNA extraction, cDNA synthesis for RNA viruses, polymerase chain reaction,
      single-strand separation, and oligonucleotide microarray analysis was performed
      in 4-4.5 h. The parallel quantification was possible in a concentration range of
      9.6 * 10(5)-1.4 * 10(10) genomic units (GU)/mL for bacteriophage MS2, 1.4 * 10(5)
      3.7 * 10(8) GU/mL for bacteriophage PhiX174, and 6.5 * 10(3)-1.2 * 10(5) for
      hAdV2, respectively, by using a measuring temperature of 40  degrees C. Detection
      limits could be calculated to 6.6 * 10(5) GU/mL for MS2, 5.3 * 10(3) GU/mL for
      PhiX174, and 1.5 * 10(2) GU/mL for hAdV2, respectively. Real samples of surface
      water and treated wastewater were tested. Generally, found concentrations of
      hAdV2, bacteriophage MS2, and PhiX174 were at the detection limit. Nevertheless,
      bacteriophages could be identified with similar results by means of quantitative
      PCR and oligonucleotide microarray analysis on the MCR 3. 

PMID- 24577575
TI  - Application of data mining methods for classification and prediction of olive oil
      blends with other vegetable oils.
AB  - The aim of this article is to study tree-based ensemble methods, new emerging
      modelling techniques, for authentication of samples of olive oil blends to check
      their suitability for classifying the samples according to the type of oil used
      for the blend as well as for predicting the amount of olive oil in the blend. The
      performance of these methods has been investigated in chromatographic fingerprint
      data of olive oil blends with other vegetable oils without needing either to
      identify or to quantify the chromatographic peaks. Different data mining methods
      classification and regression trees, random forest and M5 rules-were tested for
      classification and prediction. In addition, these classification and regression
      tree approaches were also used for feature selection prior to modelling in order
      to reduce the number of attributes in the chromatogram. The good outcomes have
      shown that these methods allow one to obtain interpretable models with much more
      information than the traditional chemometric methods and provide valuable
      information for detecting which vegetable oil is mixed with olive oil and the
      percentage of oil used, with a single chromatogram. 

PMID- 24577576
TI  - Application of liquid chromatography quadrupole time-of-flight mass spectrometry
      to the identification of acetamiprid transformation products generated under
      oxidative processes in different water matrices.
AB  - This work allowed the identification of major transformation products (TPs) of
      acetamiprid (ACTM) during Fenton process. Acetamiprid is a chloronicotinoid
      insecticide widely used around the world for its characteristics (high
      insecticidal activity, good systemic properties, suitable field stability, etc.).
      The degradation of the parent molecule and the identification of the main TPs
      were evaluated in different water matrices (demineralized water and real agro
      food industrial wastewater). TPs of acetamiprid generated by Fenton experiments
      were monitored and identified by liquid chromatography quadrupole time-of-flight
      tandem mass spectrometry (LC-QTOF-MS/MS). Up to 14 TPs were characterized based
      on the accurate mass of the molecular ion and fragment ions obtained in both full
      scan and MS/MS modes. Most of them were eliminated after 75 min of treatment time
      in demineralized water. However, in real agro-food industrial wastewater, most of
      them were eliminated at 90 min of treatment time, demonstrating the influence of
      the matrix composition on the studied compound degradation.

PMID- 24577577
TI  - Assessing hazelnut allergens by protein- and DNA-based approaches: LC-MS/MS,
      ELISA and real-time PCR.
AB  - Hazelnut (Corylus avellana L.) is responsible for a significant part of the
      allergies related to nuts. Still, it is a very much appreciated nut and as
      consequence is widely used in all types of processed foods, such as chocolates.
      Correct food labelling is currently the most effective means of preventing the
      consumption of allergenic ingredients, namely hazelnut, by the
      sensitised/allergic individuals. Thus, to verify labelling compliance and to
      ensure allergic patient protection, the development of highly sensitive
      methodologies is of extreme importance. In this study, three major methodologies,
      namely enzyme-linked immunosorbent assays (ELISA), liquid chromatography coupled
      with mass spectrometry and real-time polymerase chain reaction, were evaluated
      for their performance regarding the detection of hazelnut allergens in model
      chocolates. The sandwich ELISA and respective antibodies were in-house developed
      and produced. With sensitivity levels of approximately 1 mg kg(-1) and limits of
      quantification of 50-100 mg kg(-1), all the performed methods were considered
      appropriate for the identification of hazelnut in complex foods such as
      chocolates. To our knowledge, this was the first successful attempt to develop
      and compare three independent approaches for the detection of allergens in foods.

PMID- 24577578
TI  - Metabolomic profiling of mice urine and serum associated with trans-trans 2, 4
      decadienal induced lung lesions by liquid chromatography-mass spectrometry.
AB  - Metabolomics has become an important tool in clinical research and the diagnosis
      of human disease. Intratracheal instillation of trans-trans 2,4-decadienal (tt
      DDE), a major component in cooking oil fumes, has been demonstrated to cause lung
      lesions in mice at 8 weeks after treatment. The objective of this study was to
      identify any changes in metabolite profiles associated with the development of tt
      DDE-induced lung lesions. Using a metabolomics strategy involving a liquid
      chromatography-mass spectrometry-based approach in conjunction with principal
      component analysis and confirmation by liquid chromatography triple quadrupole
      tandem mass spectrometry, we have demonstrated that the amino acid profiles of
      the urine and serum of tt-DDE-treated mice are changed. Ten amino acids were
      significantly reduced in serum of tt-DDE-treated mice at 8 weeks after treatment.
      Our results suggest that amino acid profiles may be useful as an early indicator
      of the presence of tt-DDE-induced lung lesions.

PMID- 24577579
TI  - Determination of tributyltin in marine sediment and waters by pressurised solvent
      extraction and liquid chromatography-tandem mass spectrometry.
AB  - In this study, tributyltin (TBT) was extracted from marine sediment matrix with
      the use of pressurised solvent extraction (PSE), which uses high-temperature and 
      pressure conditions to increase extraction efficiency. The analyte was
      chromatographically resolved using a liquid chromatography-tandem mass
      spectrometry (LC-MS/MS) system with a pentafluorophenyl (PFP) column and a
      methanol/aqueous formic acid mobile phase gradient, and was detected by MS/MS as
      product fragments after collisionally induced dissociation (CID) of the cationic
      parent molecule. This study represents the first application of PSE extraction
      combined with LC-MS/MS analysis for the determination of TBT in sediments. The
      method has been validated according to the International Organisation for
      Standardisation (ISO) 17025:2001 and affords automated extraction of sediment
      samples with high-sensitivity analysis. The full method limit of detection was
      established as 1.25 ng Sn g(-1) with an instrument detection limit of 0.01 ng Sn
      g(-1). The chromatographic procedure may also be applied for the direct analysis
      of water matrices without the need for sample manipulation, and therefore
      represents a combined analytical approach for the monitoring of TBT contamination
      in marine or estuarine ecosystems. 

PMID- 24577581
TI  - A combination of metabolic labeling and 2D-DIGE analysis in response to a
      farnesyltransferase inhibitor facilitates the discovery of new prenylated
      proteins.
AB  - Protein prenylation is a post-translational modification required for proper
      cellular localization and activity of many important eukaryotic proteins.
      Farnesyltransferase inhibitors (FTIs) have been explored extensively for their
      antitumor activity. To assist in identifying potentially new and more useful
      markers for therapeutic applications, we developed a strategy that uses a
      combination of metabolic labeling and 2D DIGE (differential gel electrophoresis)
      to discover new prenylated proteins whose cellular levels are influenced by FTIs.
      In this approach, metabolic labeling of prenylated proteins was first carried out
      with an alkyne-modified isoprenoid analog, C15Alk, in the presence or absence of
      the FTI L-744,832. The resulting alkyne-tagged proteins were then labeled with
      Cy3-N3 and Cy5-N3 and subjected to 2D-DIGE. Multiple spots having altered levels
      of labeling in presence of the FTI were observed. Mass spectrometric analysis of
      some of the differentially labeled spots identified several known prenylated
      proteins, along with HisRS, PACN-3, GNAI-1 and GNAI-2, which are not known to be
      prenylated. In vitro farnesylation of a C-terminal peptide sequence derived from
      GNAI-1 and GNAI-2 produced a farnesylated product, suggesting GNAI-1 and GNAI-2
      are potential novel farnesylated proteins. These results suggest that this new
      strategy could be useful for the identification of prenylated proteins whose
      level of post-translational modification has been modulated by the presence of an
      FTI. Additionally, this approach, which decreases sample complexity and thereby
      facilitates analysis, should be applicable to studies of other post-translational
      modifications as well. 

PMID- 24577582
TI  - Nerve growth factor from cobra venom inhibits the growth of Ehrlich tumor in
      mice.
AB  - The effects of nerve growth factor (NGF) from cobra venom (cvNGF) on growth of
      Ehrlich ascites carcinoma (EAC) cells inoculated subcutaneously in mice have been
      studied. The carcinoma growth slows down, but does not stop, during a course of
      cvNGF injections and restores after the course has been discontinued. The maximal
      anti-tumor effect has been observed at a dose of 8 nmoles cvNGF/kg body weight.
      cvNGF does not impact on lifespan of mice with grafted EAC cells. K252a, a
      tyrosine kinase inhibitor, attenuates the anti-tumor effect of cvNGF indicating
      the involvement of TrkA receptors in the process. cvNGF has induced also increase
      in body weight of the experimental animals. In overall, cvNGF shows the anti
      tumor and weight-increasing effects which are opposite to those described for
      mammalian NGF (mNGF). However in experiments on breast cancer cell line MCF-7
      cvNGF showed the same proliferative effects as mNGF and had no cytotoxic action
      on tumor cells in vitro. These data suggest that cvNGF slows down EAC growth via
      an indirect mechanism in which TrkA receptors are involved. 

PMID- 24577583
TI  - Overview of scorpion species from China and their toxins.
AB  - Scorpions are one of the most ancient groups of terrestrial animals. They have
      maintained a steady morphology over more than 400 million years of evolution.
      Their venom arsenals for capturing prey and defending against predators may play
      a critical role in their ancient and conservative appearance. In the current
      review, we present the scorpion fauna of China: 53 species covering five families
      and 12 genera. We also systematically list toxins or genes from Chinese scorpion
      species, involving eight species covering four families. Furthermore, we review
      the diverse functions of typical toxins from Chinese scorpion species, involving
      Na+ channel modulators, K+ channel blockers, antimicrobial peptides and protease
      inhibitors. Using scorpion species and their toxins from China as an example, we
      build the bridge between scorpion species and their toxins, which helps us to
      understand the molecular and functional diversity of scorpion venom arsenal, the
      dynamic and functional evolution of scorpion toxins, and the potential
      relationships of scorpion species and their toxins. 

PMID- 24577584
TI  - Characterization of a novel BmalphaTX47 toxin modulating sodium channels: the
      crucial role of expression vectors in toxin pharmacological activity.
AB  - Long-chain scorpion toxins with four disulfide bridges exhibit various
      pharmacological features towards the different voltage-gated sodium channel
      subtypes. However, the toxin production still remains a huge challenge. Here, we
      reported the effects of different expression vectors on the pharmacological
      properties of a novel toxin BmalphaTX47 from the scorpion Buthus martensii
      Karsch. The recombinant BmalphaTX47 was obtained using the expression vector pET
      14b and pET-28a, respectively. Pharmacological experiments showed that the
      recombinant BmalphaTX47 was a new alpha-scorpion toxin which could inhibit the
      fast inactivation of rNa(v)1.2, mNa(v)1.4 and hNa(v)1.5 channels. Importantly,
      the different expression vectors were found to strongly affect BmalphaTX47
      pharmacological activities while toxins were obtained by the same expression and
      purification procedures. When 10 uM recombinant BmalphaTX47 from the pET-28a
      vector was applied, the values of I(5ms)/I(peak) for rNa(v)1.2, mNa(v)1.4 and
      hNa(v)1.5 channels were 44.12% +/- 3.17%, 25.40% +/- 4.89% and 65.34% +/- 3.86%,
      respectively, which were better than those values of 11.33% +/- 1.46%, 15.96% +/-
      1.87% and 5.24% +/- 2.38% for rNa(v)1.2, mNa(v)1.4 and hNa(v)1.5 channels delayed
      by 10 uM recombinant BmalphaTX47 from the pET-14b vector. The dose-response
      experiments further indicated the EC50 values of recombinant BmalphaTX47 from the
      pET-28a vector were 7262.9 +/- 755.9 nM for rNa(v)1.2 channel and 1005.8 +/-
      118.6 nM for hNa(v)1.5 channel, respectively. Together, these findings
      highlighted the important role of expression vectors in scorpion toxin
      pharmacological properties, which would accelerate the understanding of the
      structure-function relationships of scorpion toxins and promote the potential
      application of toxins in the near future.

PMID- 24577586
TI  - Beyond Parrondo's paradox.
AB  - The Parrondo's paradox is a counterintuitive phenomenon where individually-losing
      strategies can be combined in producing a winning expectation. In this paper, the
      issues surrounding the Parrondo's paradox are investigated. The focus is lying on
      testifying whether the same paradoxical effect can be reproduced by using a
      simple capital dependent game. The paradoxical effect generated by the Parrondo's
      paradox can be explained by placing all the parameters in one probability space.
      Based on this framework, it is able to generate other possible paradoxical
      effects by manipulating the parameters in the probability space. 

PMID- 24577585
TI  - Fusarium head blight control and prevention of mycotoxin contamination in wheat
      with botanicals and tannic acid.
AB  - Suspensions or solutions with 1% of Chinese galls (Galla chinensis, GC) or 1% of
      tannic acid (TA), inhibited germination of conidia or mycelium growth of Fusarium
      graminearum (FG) by 98%-100% or by 75%-80%, respectively, whereas dried bark from
      buckthorn (Frangula alnus, FA) showed no effect at this concentration. In climate
      chamber experiments where the wheat variety "Apogee" was artificially inoculated
      with FG and F. crookwellense (FCr) and treated with 5% suspensions of TA, GC and
      FA, the deoxynivalenol (DON) content in grains was reduced by 81%, 67% and 33%,
      respectively. In field experiments with two commercial wheat varieties and
      artificial or semi-natural inoculations, mean DON reductions of 66% (TA) and 58%
      (FA), respectively, were obtained. Antifungal toxicity can explain the high
      efficacies of TA and GC but not those of FA. The Fusarium head blight (FHB) and
      mycotoxin reducing effect of FA is probably due to elicitation of resistance in
      wheat plants. With semi-natural inoculation, a single FA application in the first
      half of the flowering period performed best. However, we assume that applications
      of FA at the end of ear emergence and a treatment, triggered by an infection
      period, with TA or GC during flowering, might perform better than synthetic
      fungicides. 

PMID- 24577587
TI  - Inflammatory epidermolysis bullosa acquisita effectively treated with
      minocycline.

PMID- 24577588
TI  - Invasion patterns of metastatic high-grade serous carcinoma of ovary or fallopian
      tube associated with BRCA deficiency.
AB  - High-grade serous carcinomas of the uterine adnexa with BRCA1 deficiency (high
      grade serous carcinomas-BRCA) have recently been described to demonstrate
      characteristic histopathological features. We hypothesize that metastatic high
      grade serous carcinomas-BRCA cases exhibit characteristic morphological features
      as well. We studied 102 high-grade serous carcinomas with known BRCA1 and BRCA2
      genotype from the archives of the Department of Pathology at Memorial Sloan
      Kettering Cancer Center. The primary site morphological characteristics of these
      cases were reported previously; we now focus solely on tumor morphology in sites
      other than the uterine adnexa (ie, metastatic sites). The study group consisted
      of the following case types: 13 BRCA1 germline mutations; 5 BRCA1 somatic
      mutations; 10 BRCA1 promoter methylation; 4 BRCA2 germline mutations; 1 BRCA2
      somatic mutation; 11 lacking BRCA1 or BRCA2 abnormality; 58 cases lacking BRCA1
      or BRCA2 germline mutation. Two observers independently scored invasion patterns
      and microscopic tumor architecture while blinded to genotype. Concordance between
      observers and correlations between metastatic patterns and the following indices
      were studied: genotype, primary site tumor characteristics, and BRCA1
      immunohistochemistry. Concordance between observers was excellent (kappa values
      >0.9). All cases with BRCA1 or 2 abnormalities showed either pushing pattern
      metastases (76%) or infiltrative metastases composed only of micropapillae (24%).
      In contrast, all cases lacking BRCA1 or 2 abnormalities showed infiltrative
      metastases that contained combinations of papillary, glandular, and, rarely,
      cribriform and micropapillary architecture (P<0.0001 for comparison with pushing
      metastasis and P<0.001 for comparison with purely micropapillary architecture).
      Morphological assessment of metastatic carcinomas, a highly reproducible
      exercise, accurately correlated with BRCA1 status in every case, unlike
      morphological assessment of primary site adnexal high-grade serous carcinomas or
      BRCA1 immunohistochemistry. Metastatic high-grade serous carcinomas-BRCAs exhibit
      characteristic morphological features that appear more sensitive and specific for
      BRCA mutations than two other morphologically based prediction systems and should
      be easier to apply in practice. These findings should be validated prospectively
      in an independent cohort. 

PMID- 24577590
TI  - Genetic testing and the health care system.

PMID- 24577589
TI  - epsilon-MnO2 nanostructures directly grown on Ni foam: a cathode catalyst for
      rechargeable Li-O2 batteries.
AB  - A sponge-like epsilon-MnO2 nanostructure was synthesized by direct growth of
      epsilon-MnO2 on Ni foam through a facile electrodeposition route. When applied as
      a self-supporting, binder-free cathode material for rechargeable nonaqueous
      lithium-oxygen batteries, the epsilon-MnO2/Ni electrode exhibits considerable
      high-rate capability (discharge capacity of ~6300 mA h g(-1) at a current density
      of 500 mA g(-1)) and enhanced cyclability (exceeding 120 cycles) without
      controlling the discharge depth. The superior performance is proposed to be
      associated with the 3D nanoporous structures and abundant oxygen defects as well
      as the absence of side reactions related to carbon-based conductive additives and
      binders. 

PMID- 24577591
TI  - Reputation, public information, and physician adoption of an innovation.
AB  - A dynamic expected utility framework is developed to explore the timing and
      extent of a physician's adoption of an innovation. The benefits to adoption are
      uncertain, although an informative public information signal is released with
      some delay and possibly some inaccuracy. Improvements to the accuracy of the
      signal do not necessarily cause risk-averse physicians to scale back adoption
      prior to the signal's release - if physicians are confident enough in the
      innovation's worth, they may accelerate early adoption in order to capture an
      earlymover advantage in reputation building. 

PMID- 24577592
TI  - Costs of opioid therapy for chronic nonmalignant pain in Germany: an economic
      model comparing transdermal fentanyl (Durogesic) with controlled-release
      morphine.
AB  - The fentanyl transdermal therapeutic system (fentanyl-TTS;Durogesic) has a
      distinct route of administration and safety profile compared with other opioids
      used in the treatment of moderate to severe pain.These aspects are likely to have
      an impact on patient acceptance and functioning as well as efficacy. We compared
      the cost-utility of fentanyl-TTS and controlled-release morphine (cr-morphine) in
      the treatment of moderate to severe nonmalignant pain in outpatients in Germany.
      A 1-year, three-phased decisionanalytic model was constructed, incorporating
      estimates of a variety of aspects of pain control.Use of fentanyl-TTS was
      predicted to incur higher costs than cr-morphine over 1 year of treatment (DM
      6950 vs.DM 6186, respectively) but was associated with a higher number of quality
      adjusted life days (234 vs. 216, respectively), thus achieving an incremental
      cost-utility ratio of DM 15,960 per quality-adjusted life-year gained.The results
      of the decision-analytic model support the use of fentanyl-TTS as a favorable
      cost-effective option for the treatment of moderate to severe nonmalignant pain. 

PMID- 24577594
TI  - Erratum to: Does health technology assessment benefit health services and
      politics? : The experiences of an established HTA institution: the Danish Centre
      for Evaluation and HTA.

PMID- 24577593
TI  - Association of time preference for health with age and disease severity.
AB  - This study assessed the relationship between time preference for health and age
      and disease severity. An implicit time preference for health was inferred in 59
      patients with chronic obstructive pulmonary disease (COPD) using the time
      tradeoff method with 10-year and 30-year perspectives. The preference rate was
      calculated by solving the resulting nonlinear equation, solvable for 50
      patients.Among the resulting rates, 4 were negative, 8 zero, and 38 positive. The
      time preference rate ranged from -10.8% to 75.0%, with a median of 6.6%, and a
      mean of 11.5%. In correlation analysis, the implicit time preference rate was
      associated with age;however, there was little association with markers of disease
      severity. In multivariate analysis, only age was a significant predictor of time
      preference rate after controlling for the other variables in the model. 

PMID- 24577595
TI  - Time for a change in drug licensing requirements?

PMID- 24577596
TI  - Commentary : On Drummond's "Time for a change in drug licensing requirements?".

PMID- 24577597
TI  - Commentary : On Drummond's "Time for a change in drug licensing requirements?".

PMID- 24577598
TI  - Time for a change in drug pricing : Going downstream : Comment on Drummond's
      short paper.

PMID- 24577599
TI  - Drug licensing requirements are changing! : Comment on Drummond's short paper.

PMID- 24577600
TI  - A final comment.

PMID- 24577602
TI  - Are there really indications for central pancreatectomy?

PMID- 24577601
TI  - The association between physical activity and maternal sleep during the
      postpartum period.
AB  - Physical activity is associated with improved sleep quality and duration in the
      general population, but its effect on sleep in postpartum women is unknown. We
      examined cross-sectional and longitudinal associations between hours/week of self
      reported domain-specific and overall moderate to vigorous physical activity
      (MVPA) and sleep quality and duration at 3- and 12-months postpartum among a
      cohort of 530 women in the Pregnancy, Infection, and Nutrition Postpartum Study.
      MVPA was not associated with sleep quality or duration at 3-months postpartum. At
      12-months postpartum, a 1 h/week increase in recreational MVPA was associated
      with higher odds of good (vs. poor) sleep quality (odds ratio, OR 1.14; 95 %
      confidence interval, CI, 1.03-1.27) and a 1 h/week increase in child/adult care
      MVPA was associated with lower odds of good (vs. poor) sleep quality (OR = 0.93;
      95 % CI 0.88-0.99). A 1 h/week increase in child/adult care MVPA (OR 1.08, 95 %
      CI 1.00-1.16) was associated with higher odds of long sleep duration and 1 h/week
      increases in indoor household (OR 1.09, 95 % CI 1.01-1.18) and overall MVPA (OR
      1.04, 95 % CI 1.01-1.07) were associated with higher odds of short (vs. normal)
      sleep duration. Comparing 3-months postpartum to 12-months postpartum, increased
      work MVPA was associated with good sleep quality (OR 2.40, 95 % CI 1.12-5.15) and
      increased indoor household MVPA was associated with short sleep duration (OR
      1.85, 95 % CI 1.05-3.27) as measured at 12-months postpartum. Selected domains of
      MVPA and their longitudinal increases were associated with sleep quality and
      duration at 12-months postpartum. Additional research is needed to elucidate
      whether physical activity can improve postpartum sleep.

PMID- 24577605
TI  - Unidirectional light-driven molecular motors based on overcrowded alkenes.
AB  - Over the last two decades, interest in nanotechnology has led to the design and
      synthesis of a toolbox of nanoscale versions of macroscopic devices and
      components. In molecular nanotechnology, linear motors based on rotaxanes and
      rotary motors based on overcrowded alkenes are particularly promising for
      performing work at the nanoscale. In this chapter, progress on light-driven
      molecular motors based on overcrowded alkenes is reviewed. Both the so-called
      first and second generation molecular motors are discussed, as well as their
      potential applications. 

PMID- 24577604
TI  - A TB antigen-stimulated CXCR3 ligand assay for the diagnosis of active pulmonary
      TB.
AB  - BACKGROUND: The ligands for CXC chemokine receptor 3 (CXCR3) recruit T-helper
      type 1 cells, which play a major role in cell-mediated immunity in TB. METHODS: A
      total of 409 subjects were enrolled. The study population comprised 186 patients
      with active TB, 58 patients with non-TB pulmonary diseases, 50 control subjects
      with a positive interferon (IFN)-gamma release assay (IGRA) result, and 115
      control subjects with a negative IGRA result. Whole-blood samples were collected
      using IGRA methodology. After incubation, plasma IFN-gamma levels and two CXCR3
      ligands, IFN-inducible T-cell alpha-chemoattractant (I-TAC, CXCL11) and monokine
      induced by IFN-gamma (MIG, CXCL9), were measured by enzyme-linked immunosorbent
      assay. Receiver operating characteristic (ROC) analysis was performed.
      Sensitivity and specificity were based on cutoff values selected to maximize the
      Youden index. RESULTS: The TB antigen-stimulated levels of IFN-gamma, I-TAC, and
      MIG were significantly increased in the active pulmonary TB group compared with
      all other groups. From ROC analysis, for the diagnosis of active TB, I-TAC and
      MIG outperformed IFN-gamma in all comparisons with the IGRA-positive and 
      negative control groups and the non-TB pulmonary disease group. The areas under
      the curve (95% CI) for differentiating active pulmonary TB from all other groups
      were 0.893 (0.864-0.924) for IFN-gamma, 0.962 (0.946-0.978) for I-TAC, and 0.944
      (0.922-0.965) for MIG. Sensitivity and specificity were 90.3% and 90.7%,
      respectively, for I-TAC; 92.5% and 85.2% for MIG; and 84.9% and 79.8% for IFN
      gamma. CONCLUSIONS: TB antigen-stimulated assays of I-TAC and MIG may be useful
      surrogate markers in the diagnosis of active pulmonary TB.

PMID- 24577603
TI  - An alphanubeta3 integrin-binding peptide ameliorates symptoms of chronic
      progressive experimental autoimmune encephalomyelitis by alleviating
      neuroinflammatory responses in mice.
AB  - MOG35-55 triggers chronic, progressive experimental autoimmune encephalomyelitis
      (EAE) in C57BL/6 mice, and the clinical course of EAE in this model is
      characterized by macrophage infiltration, axonal demyelination/damage, and
      progressive paralysis. These stages are usually associated with inflammatory
      responses in the central nervous system (CNS). This study was designed to
      investigate the effects of C16, an alphanubeta3 integrin-binding peptide that
      targets integrins involved in the transendothelial migration of extravasating
      inflammatory cells. C16 was applied for only 2 weeks, but the benefits of this
      therapy lasted at least 8 weeks. Multiple histological and immunohistochemical
      staining studies, western blotting, enzyme-linked immunosorbent assays, electron
      microscopy, and cortical somatosensory-evoked potential (c-SEP)
      electrophysiological tests were employed to assess the degree of inflammation,
      axonal loss, white matter demyelination, neuronal apoptosis, extent of gliosis,
      expression of pro-inflammatory cytokines, and functional recovery of differently
      treated EAE model mice. The results showed that C16 treatment inhibited extensive
      leukocyte and macrophage accumulation and infiltration, reduced the expression of
      pro-inflammatory cytokines (tumor necrosis factor-alpha and interferon-gamma),
      and thereby attenuated and delayed the progression of EAE. Moreover,
      astrogliosis, demyelination, and axonal and neuronal loss were all alleviated in
      C16-treated EAE animals, contributing to the improvement of function. These data
      suggest that the C16 peptide may act as a protective agent by reducing
      neuroinflammatory responses and improving the microenvironment. 

PMID- 24577606
TI  - Organizing mechanically interlocked molecules to function inside metal-organic
      frameworks.
AB  - The idea that the workings of molecular switches, motors, and machines based on
      mechanically interlocked molecules can be transferred into the solid state by
      using them as the building blocks of metal-organic framework materials is
      addressed. This involves an in-depth review and analysis of the chemistry of
      coordination polymers and metal-organic frameworks in which the linkers are
      rotaxanes and catenanes. To date, two types of materials have been prepared: (1)
      coordination polymers in which the interlocked components are part of a complex
      architecture but do not display large amplitude molecular motion or function and
      (2) those that clearly demonstrate some type of supramolecular quality (molecular
      recognition) or relative motion between interlocked components (dynamics)
      reminiscent of their solution counterparts. The latter can be thought of as
      prototypes of solid-state molecular machines. The possibility of creating more
      sophisticated, solid-state materials that have the full characteristics of
      molecular switches, motors, and machines and the way forward for this chemistry
      is also discussed. 

PMID- 24577607
TI  - Spin excitations in solids from many-body perturbation theory.
AB  - Collective spin excitations form a fundamental class of excitations in magnetic
      materials. As their energy reaches down to only a few meV, they are present at
      all temperatures and substantially influence the properties of magnetic systems.
      To study the spin excitations in solids from first principles, we have developed
      a computational scheme based on many-body perturbation theory within the full
      potential linearized augmented plane-wave (FLAPW) method. The main quantity of
      interest is the dynamical transverse spin susceptibility or magnetic response
      function, from which magnetic excitations, including single-particle spin-flip
      Stoner excitations and collective spin-wave modes as well as their lifetimes, can
      be obtained. In order to describe spin waves we include appropriate vertex
      corrections in the form of a multiple-scattering T matrix, which describes the
      coupling of electrons and holes with different spins. The electron-hole
      interaction incorporates the screening of the many-body system within the random
      phase approximation. To reduce the numerical cost in evaluating the four-point T
      matrix, we exploit a transformation to maximally localized Wannier functions that
      takes advantage of the short spatial range of electronic correlation in the
      partially filled d or f orbitals of magnetic materials. The theory and the
      implementation are discussed in detail. In particular, we show how the magnetic
      response function can be evaluated for arbitrary k points. This enables the
      calculation of smooth dispersion curves, allowing one to study fine details in
      the k dependence of the spin-wave spectra. We also demonstrate how spatial and
      time-reversal symmetry can be exploited to accelerate substantially the
      computation of the four-point quantities. As an illustration, we present spin
      wave spectra and dispersions for the elementary ferromagnet bcc Fe, B2-type
      tetragonal FeCo, and CrO2 calculated with our scheme. The results are in good
      agreement with available experimental data.

PMID- 24577608
TI  - Photoinduced charge-separation in DNA.
AB  - DNA site-specifically modified with a photosensitizer (Sens) was synthesized and
      the charge-separation and charge-recombination dynamics in DNA were studied. We
      specifically focused on the formation of the long-lived charge-separated state
      whose lifetime (tau) is longer than 0.1 MUs. The quantum yields of the formation
      of the charge-separated states (Phi) upon the photoexcitation of the Sens, and
      the tau were measured using the laser flash photolysis technique. We utilized
      naphthalimide (NI), naphthaldiimide (ND), and anthraquinone (AQ) as a Sens to
      investigate the mechanism of the formation of the charge-separated state in DNA
      via rapid positive charge (hole) transfer between adenine and thymine (A-T) base
      pairs. By replacing some T bases in the A-T stretch with 5-bromouracil ((br)U),
      the charge-separation was shown to occur via the photoinduced charge-injection
      into the second and further neighboring As to the Sens. On the other hand, the
      generation of a hole on A nearest to Sens ends up with the rapid charge
      recombination within a contact ion pair. A long-lived charge-separated state was
      also generated in DNA when a commonly used fluorophore such asTAMRA, Alexa 532,
      and ATTO 655, which can only oxidize guanine-cytosine (G-C) base-pair, but not A
      T, was used as a Sens. These results suggested that the charge-separation in DNA
      is a general phenonmenon for fluorescent dyes which fluorescence is quenched only
      by G-C.

PMID- 24577609
TI  - Prediction and theoretical characterization of p-type organic semiconductor
      crystals for field-effect transistor applications.
AB  - The theoretical prediction and characterization of the solid-state structure of
      organic semiconductors has tremendous potential for the discovery of new high
      performance materials. To date, the theoretical analysis mostly relied on the
      availability of crystal structures obtained through X-ray diffraction. However,
      the theoretical prediction of the crystal structures of organic semiconductor
      molecules remains a challenge. This review highlights some of the recent advances
      in the determination of structure-property relationships of the known organic
      semiconductor single-crystals and summarizes a few available studies on the
      prediction of the crystal structures of p-type organic semiconductors for
      transistor applications. 

PMID- 24577612
TI  - Differential expression of two-component systems, pmrAB and phoPQ, with different
      growth phases of Klebsiella pneumoniae in the presence or absence of colistin.
AB  - We explored whether expression of pmrAB, pmrD, and phoPQ is dependent on growth
      phase with or without colistin exposure in colistin-resistant Klebsiella
      pneumoniae strains. In four colistin-resistant K. pneumoniae strains, the
      expression of pmrAB, pmrD, and phoPQ was evaluated at mid-log, late-log, and
      stationary phases in the absence or presence of colistin, by qRT-PCR. The
      expression pattern in the presence of colistin was different from that in the
      absence of colistin: overall, pmrAB, pmrD, and phoPQ expressed the highest at the
      stationary phase in the absence of colistin, but the expression of pmrD and phoPQ
      decreased with the growth in the presence of colistin. Exposure to colistin might
      change the expression patterns of two-component regulatory systems in colistin
      resistant K. pneumoniae strains.

PMID- 24577613
TI  - Transcriptional regulation mechanism of ter operon by OxyR in Yersinia pestis.
AB  - The aim of this work was to study the transcriptional regulation mechanism of ter
      operon by OxyR in Yersinia pestis. Total RNAs were extracted from the wild-type
      (WT) strain and the oxyR null mutant (DeltaoxyR) strain. Primer extension assay
      was employed to detect the promoter activity (the amount of primer extension
      product) of terZ in WT and DeltaoxyR. terZ promoter-proximal region was cloned
      into the pRW50 plasmid containing a promoterless lacZ gene. The recombinant LacZ
      reporter plasmid was transformed into WT and DeltaoxyR, respectively, to measure
      the promoter activity (the beta-galactosidase activity) of terZ in WT and
      DeltaoxyR by using the beta-galactosidase enzyme assay system. The entire
      promoter-proximal region of the terZ gene was amplified by PCR from Y. pestis
      strain 201, and the over-expressed His-OxyR was also purified under native
      conditions with nickel loaded HiTrap Chelating Sepharose columns (Amersham).
      Electrophoretic mobility shift assay was applied to analyze the DNA-binding
      activity of His-OxyR to terZ promoter region in vitro. Primer extension assay
      detected only one transcriptional start site located at 50 bp upstream of terZ,
      whose transcript was directly activated by OxyR in Y. pestis. The EMSA result
      shows that His-OxyR has the ability to bind to the upstream DNA region of terZ.
      The transcription of ter operon was found to be directly activated by OxyR in Y.
      pestis.

PMID- 24577614
TI  - Improving the efficiency of the modified Hodge test in KPC-producing Klebsiella
      pneumoniae isolates by incorporating an EDTA disk.
AB  - Carbapenemase-producing Klebsiella pneumoniae have emerged as an important
      pathogens in nosocomial infections with high mortality rate. Although the
      modified Hodge test (MHT) is recommended for phenotypic detection of
      carbapenemase-producing Enterobacteriaceae, high false-positive rates were
      reported for MHT results. The MHT has acceptable sensitivity (98.0 %), but it
      lacks specificity (73.6 %). In this study, we incorporated an EDTA disk test into
      the MHT (MHT-EDTA) to improve the efficiency in phenotypic detection of K.
      pneumoniae carbapenemase (KPC) of K. pneumoniae isolates. EDTA was used to lyse
      the cells of 123 carbapenem non-susceptible K. pneumoniae isolates to release the
      beta-lactamases. The MHT-EDTA achieved 100 % sensitivity and specificity for KPC
      detection among K. pneumoniae isolates as compared to growth patterns of the
      indicator organism E. coli (ATCC 25922). This method could be carried out as part
      of routine work to provide useful information for the clinical management of K.
      pneumoniae infection.

PMID- 24577615
TI  - An algorithmic approach for managing orthopaedic surgical wounds of the foot and
      ankle.
AB  - BACKGROUND: Wound breakdown after orthopaedic foot and ankle surgery may
      necessitate secondary soft tissue coverage. The foot and ankle region is
      challenging to reconstruct for orthopaedic and plastic surgeons owing to its
      complex bony anatomy and unique functional demands. Therefore, identifying
      strategies for plastic surgery of these wounds may help guide surgeons in
      defining the best treatment plan. QUESTIONS/PURPOSES: We evaluated our current
      algorithmic approach for managing orthopaedic surgical wounds of the foot and
      ankle with respect to whether (1) prophylactic or simultaneous soft tissue
      coverage affected wound-healing complications (secondary plastic surgery,
      orthopaedic hardware removal, malunion, further orthopaedic surgery, ultimate
      failure) and (2) postoperative referral for soft tissue management was associated
      with wound location, size, and orthopaedic procedure. METHODS: We retrospectively
      reviewed 112 patients who underwent elective orthopaedic foot or ankle surgery
      and required concomitant plastic surgery at our institution. Study end points
      included secondary plastic surgery procedures, hardware removal for infection,
      foot or ankle malunion, further orthopaedic surgery, and wound-healing failure as
      defined by a chronic nonhealing wound or need for amputation. Minimum followup
      was 0.6 months (mean, 24.9 months; range, 0.6-197 months). Four patients were
      lost to complete followup. We developed an algorithm that centers on two critical
      points of care: preoperative evaluation by the orthopaedic surgeon and evaluation
      and treatment by the plastic surgeon after referral. RESULTS: Compared with
      postoperative intervention, prophylactic or simultaneous soft tissue coverage did
      not lead to differences in frequency of secondary plastic surgery procedures (p =
      0.55), hardware removal procedures (p = 0.13), malunions (p = 0.47), further
      orthopaedic surgery (p = 0.48), and ultimate failure (p = 0.27). Patients
      referred postoperatively for soft tissue management most frequently had dorsal
      ankle wounds (p < 0.001) of smaller size (p = 0.03), most commonly associated
      with total ankle arthroplasty (p = 0.004). CONCLUSIONS: Using our algorithmic
      approach, prophylactic or simultaneous soft tissue coverage did not improve the
      study end points. In addition, unexpected postoperative wound breakdown
      necessitating a plastic surgery consultation most commonly occurred on the dorsal
      ankle after total ankle arthroplasty. Our algorithm facilitates early
      identification of skin instability and enables prompt soft tissue coverage before
      or concurrently with orthopaedic procedures. The effect of prophylactic or
      simultaneous soft tissue coverage on postoperative wound healing requires further
      investigation. LEVEL OF EVIDENCE: Level IV, therapeutic study. See the
      Instructions for Authors for a complete description of levels of evidence.

PMID- 24577617
TI  - Simultaneous elimination of carryover contamination and detection of DNA with
      uracil-DNA-glycosylase-supplemented loop-mediated isothermal amplification (UDG
      LAMP).
AB  - We report a one-pot, closed-vessel enzymatic assay that eliminates carryover
      contamination while preserving robust DNA amplification in loop-mediated
      isothermal amplification (LAMP), providing reliable and rapid detection of target
      DNA in contaminated samples. 

PMID- 24577616
TI  - Is ORIF superior to nonoperative treatment in isolated displaced partial
      articular fractures of the radial head?
AB  - BACKGROUND: While good results have been reported with both nonoperative and
      operative treatment of isolated displaced partial radial head fractures, there
      remains considerable disagreement about the role of surgery in the management of
      these injuries. QUESTIONS/PURPOSES: We (1) compared isolated displaced partial
      articular radial head fractures treated nonoperatively with open reduction
      internal fixation (ORIF) in terms of validated outcomes scores, ROM, and
      strength; (2) assessed whether there were any predictor variables for outcomes;
      and (3) compared complications between groups. METHODS: We retrospectively
      compared patients with isolated partial articular radial head fractures displaced
      greater than 2 mm but less than 5 mm who received either nonoperative treatment
      (30 patients) or ORIF (30 patients). We reviewed the nonoperative and ORIF groups
      at a mean of 3 and 4.5 years, respectively. The nonoperative and ORIF groups were
      similar except for age (51 +/- 17 years versus 39 +/- 10 years, respectively) and
      fracture displacement (2.3 +/- 0.3 mm versus 2.8 +/- 0.6 mm, respectively). As
      there were no definitive guidelines on which treatment represented best
      management, treatment type was decided by the attending surgeon in conjunction
      with the patient on a case-by-case basis. Patients were evaluated using the
      Patient-rated Elbow Evaluation (PREE) (primary outcome measure), Mayo Elbow
      Performance Score (MEPS), QuickDASH, SF-12, clinical examination, and
      radiographic evaluation (14 and 28 in the nonoperative and ORIF groups,
      respectively). Elbow ROM was assessed with a goniometer and hand grip strength
      with calibrated strength testing. We assessed possible predictive variables (age,
      displacement, energy of injury) for clinical outcome scores and recorded
      complications. RESULTS: PREE scores were not different between groups, but the
      MEPS favored the nonoperative group (93 versus 86; p = 0.012). ROM and grip
      strength were similar between groups. Younger age was associated with worse
      outcome, but displacement and energy were not. More complications occurred in the
      ORIF group (eight cases of mild heterotopic ossification, two cases of hardware
      failure) than in the nonoperative group (one case of mild heterotopic
      ossification, one case of complex regional pain syndrome). CONCLUSIONS: No
      clinical benefit with ORIF could be found compared to nonoperative management of
      isolated partial articular radial head fractures with displacement of greater
      than 2 mm but less than 5 mm at short-term followup. A well-designed randomized
      trial and followup at longer term are required to provide better information
      about how to treat these common fractures. LEVEL OF EVIDENCE: Level III,
      therapeutic study. See Instructions for Authors for a complete description of
      levels of evidence.

PMID- 24577619
TI  - Antepartum uterine rupture in a twin gestation presenting as an advanced
      extrauterine pregnancy in a patient with a previous lower segment Caesarean
      section.
AB  - We present a case of spontaneous antepartum uterine rupture through a previous
      lower segment Caesarean section (LSCS) scar with clinical features mimicking an
      advanced extrauterine pregnancy (AEUP) in a twin pregnancy at 28 weeks gestation.
      This report illustrates the need to consider a diagnosis of a ruptured uterus in
      any patient with a previous abdominal delivery who presents with mild abdominal
      tenderness and an ultrasonographic image suggestive of demised fetus in the intra
      peritoneal cavity. 

PMID- 24577621
TI  - Risks associated with the mining of Pb-Zn minerals in some parts of the Southern
      Benue trough, Nigeria.
AB  - The environmental effects of the mining of lead-zinc mineralization in Enyigba
      area, Southern Benue trough were examined. The samples used for this study were
      obtained from abandoned mine sites, mine tailings, streams, hand-dug wells, mine
      pond and borehole. Collected samples were subjected to X-ray fluorescence, X-ray
      diffraction analyses, atomic absorption spectrometry and permeability tests.
      These were done using standard laboratory equipment and procedures. The
      concentrations of heavy metals present in analysed water samples fall below the
      world health organizations' (WHO) acceptable limits. Conversely, the soil, mine
      tailings and stream sediments indicate appreciable pollution level by some
      potential toxic metals (PTMs). Consequently, the habitual use of these soils for
      construction purpose by inhabitants has possible health hazards. The shaly
      lithology underlying the area is increasingly affected by weathering and
      lateritization, thus improving its permeability and the easiness with which PTMs
      can be conducted to the water table by leachate. Regular monitoring assessment is
      recommended to ensure adherence of miners operating in the area to existing
      environmental laws.

PMID- 24577620
TI  - 8p22-23-rs2254546 as a susceptibility locus for Kawasaki disease: a case-control
      study and a meta-analysis.
AB  - 8p22-23-rs2254546 was firstly discovered to be associated with Kawasaki disease
      (KD) susceptibility by a genome-wide association study. However, only one Chinese
      replication study has been performed so far. To verify this association in
      another Chinese population, a hospital-based case-control study in Zhejiang
      province was conducted followed by an integrated meta-analysis, comprising five
      case-control studies of 1958 cases, 5615 controls and four transmission
      disequilibrium tests of 503 trios. In our case-control study, significant
      associations were observed between GG genotype or GG/GA genotypes of rs2254546
      and increased KD risk (OR = 1.86, 95% CI = 1.01-3.41, P = 0.045; OR = 1.83, 95%
      CI = 1.01-3.33, P = 0.048), compared with AA genotype; however, no significant
      association was found in allelic model (OR = 1.20, 95% CI = 0.96-1.50, P =
      0.117). The meta-analysis further revealed that the G allele was significantly
      associated with the increased KD risk without evidence of heterogeneity (OR =
      1.55, 95% CI = 1.42-1.70, P < 0.001). In conclusion, rs2254546 polymorphism might
      significantly contribute to the risk of KD. 

PMID- 24577622
TI  - Calcium signalling and psychiatric disease: bipolar disorder and schizophrenia.
AB  - Neurons have highly developed Ca(2+) signalling systems responsible for
      regulating many neural functions such as the generation of brain rhythms,
      information processing and the changes in synaptic plasticity that underpins
      learning and memory. The signalling mechanisms that regulate neuronal
      excitability are particularly important for processes such as sensory perception,
      cognition and consciousness. The Ca(2+) signalling pathway is a key component of
      the mechanisms responsible for regulating neuronal excitability, information
      processing and cognition. Alterations in gene transcription are particularly
      important as they result in subtle alterations in the neuronal signalling
      mechanisms that have been implicated in many neural diseases. In particular,
      dysregulation of the Ca(2+) signalling pathway has been implicated in the
      development of some of the major psychiatric diseases such as bipolar disorder
      (BPD) and schizophrenia. 

PMID- 24577624
TI  - Genetic analysis of CARD14 in non-familial pityriasis rubra pilaris: a case
      series.

PMID- 24577623
TI  - Gender and the active smoking and high-sensitivity C-reactive protein relation in
      late adolescence.
AB  - C-reactive protein (CRP), smoking, and oral contraceptive (OC) use are associated
      with CVD risk in adults. This study examines the effect of smoking on high
      sensitivity CRP (hs-CRP) levels, and the interactive effects of sex and OC use on
      this relationship in an adolescent cohort. A total of 1,050 adolescents (mean age
      17 +/- 0.25 years) from the Western Australian Pregnancy Cohort (Raine) Study had
      anthropometric, lifestyle, and metabolic measures recorded. The association
      between smoking status and log-transformed hs-CRP was analyzed using
      multivariable Tobit linear regression models, with adjustment for adiposity,
      lifestyle, and early-life confounders. A three-level variable (girls not using
      OCs, girls using OCs, and boys) was employed to assess the interactive effects of
      sex, OC use, and smoking. Smoking associated with higher hs-CRP levels in girls
      not using OCs (b = 0.571; P = 0.001), but not in girls using OCs (b = -0.117; P =
      0.598) or in boys (b = 0.183; P = 0.2). OC use in nonsmoking girls was the
      strongest factor associated with higher hs-CRP levels (b = 1.189; P < 0.001).
      This study has demonstrated a more robust effect of smoking on hs-CRP levels in
      girls not using OCs compared with boys. The findings may explain why CVD risk
      conferred by smoking is higher in women than in men. 

PMID- 24577625
TI  - Relationship of muscle sympathetic nerve activity to insulin sensitivity.
AB  - PURPOSE: An association between insulin resistance and activation of the
      sympathetic nervous system has been reported in previous studies. However,
      potential interactions between insulin sensitivity and sympathetic neural
      mechanisms in healthy people remain poorly understood. We conducted a study to
      determine the relationship between sympathetic activity and insulin resistance in
      young, healthy humans. METHODS: Thirty-seven healthy adults (18-35 years, BMI <28
      kg m(-2)) were studied. Resting muscle sympathetic nerve activity (MSNA) was
      measured with microneurography and insulin sensitivity of glucose and free fatty
      acid metabolism was measured during a hyperinsulinemic-euglycemic clamp with two
      levels of insulin. RESULTS: During lower doses of insulin, we found a small
      association between lower insulin sensitivity and higher MSNA (P < 0.05) but age
      was a cofactor in this relationship. Overall, we found no difference in insulin
      sensitivity between groups of low and high MSNA, but when women were analyzed
      separately, insulin sensitivity was lower in the high MSNA group compared with
      the low MSNA group of women. CONCLUSIONS: These data suggest that MSNA and
      insulin sensitivity are only weakly associated with young healthy individuals and
      that age and sex may be important modifiers of this relationship.

PMID- 24577627
TI  - Correlation of missed doses of enoxaparin with increased incidence of deep vein
      thrombosis in trauma and general surgery patients.
AB  - IMPORTANCE: Enoxaparin sodium is widely used for deep vein thrombosis (DVT)
      prophylaxis, yet DVT rates remain high in the trauma and general surgery
      populations. Missed doses during hospitalization are common. OBJECTIVE: To
      determine if missed doses of enoxaparin correlate with DVT formation. DESIGN,
      SETTING, AND PARTICIPANTS: Data were prospectively collected among 202 trauma and
      general surgery patients admitted to a level I trauma center. MAIN OUTCOMES AND
      MEASURES: Deep vein thrombosis screening was performed using a rigorous
      standardized protocol. RESULTS: The overall incidence of DVT was 15.8%. In total,
      58.9% of patients missed at least 1 dose of enoxaparin. The DVTs occurred in
      23.5% of patients who missed at least 1 dose and in 4.8% of patients who did not
      (P < .01). On univariate analysis, the need for mechanical ventilation (71.8% vs
      44.1%), the performance of more than 1 operation (59.3% vs 40.0%), and male sex
      (75% vs 56%) were associated with DVT formation (P < .05 for all). A bivariate
      logistic regression was then performed, which revealed age 50 years or older and
      interrupted enoxaparin therapy as the only independent risk factors for DVT
      formation. The DVT rate did not differ between trauma and general surgery
      populations or in patients receiving once-daily vs twice-daily dosing regimens.
      CONCLUSIONS AND RELEVANCE: Interrupted enoxaparin therapy and age 50 years or
      older are associated with DVT formation among trauma and general surgery
      patients. Missed doses occur commonly and are the only identified risk factor for
      DVT that can be ameliorated by physicians. Efforts to minimize interrupted
      enoxaparin prophylaxis in patients at risk for DVT should be optimized.

PMID- 24577626
TI  - Temsirolimus and pegylated liposomal doxorubicin (PLD) combination therapy in
      breast, endometrial, and ovarian cancer: phase Ib results and prediction of
      clinical outcome with FDG-PET/CT.
AB  - Pegylated liposomal doxorubicin (PLD) is active in breast, endometrial, and
      ovarian cancer. Preclinical data suggest that the combination of PLD with a
      mammalian target of rapamycin (mTOR) inhibitor has an additive effect. The safety
      and recommended phase two dose (RPTD) of temsirolimus in combination with PLD
      were assessed. (18) F-fluorodeoxyglucose (FDG) positron emission tomography
      (PET)/CT was performed for early response monitoring. Nineteen patients with
      advanced breast, endometrial, and ovarian cancer were treated with increasing
      doses of temsirolimus (10, 15, or 20 mg once weekly) and PLD (30 or 40 mg/m(2)
      once every 4 weeks). PLD was initiated 2 weeks after start of temsirolimus. FDG
      PET/CT was performed at baseline, after 2 and 6 weeks. Standardized uptake values
      (SUV), metabolic volume, and total lesion glycolysis (TLG, SUV * metabolic
      volume) were calculated. The RPTD was 15 mg temsirolimus and 40 mg/m(2) PLD. Dose
      limiting toxicities (DLT) were thrombocytopenia grade 3 with nose bleeding and
      skin toxicity grade 3. Most frequent treatment-related toxicities were nausea,
      fatigue, mucositis, and skin toxicity. Changes in TLG after 2 weeks predicted
      partial response (PR) after 10 weeks (p = 0.037). A rise in SUV between the
      second and sixth week predicted progression (PD) (p = 0.034) and was associated
      with worse progression free survival (PFS) (HR 1.068; p = 0.013). The RPTD was
      established at 15 mg temsirolimus weekly and PLD 40 mg/m(2) once every 4 weeks
      and the combination was safe. Early response evaluation with FDG-PET/CT may
      predict subsequent radiological PR and PD. This trial is registered under number
      NCT0098263. 

PMID- 24577628
TI  - 3D-tracking the regenerative potential of the mandible with micro-CTs.
AB  - PURPOSE: The treatment of large bone defects is a challenging problem especially
      when the mandible is affected. Bone healing is dependent on the defect size and
      the integrity of periosteum. So far, these both aspects have not been
      investigated separately. The aim of this study was to evaluate the healing
      potential of the mandibular bone with the help of three-dimensional micro
      computed tomography (CT). METHODS: The angle of the mandible was exposed in 15
      Wistar rats. A 3-mm core of bone was removed with a trephine. The local
      periosteum next to the defect was excised. Animals were randomized in five
      groups, which were ended 5, 10, 15, 28 and 56 days after operation. The mandible
      was excised and underwent micro-CT. For statistical evaluation, t-test statistics
      and regression analysis were applied. RESULTS: Characteristics of the defects
      began to change on the tenth postoperative day. Fifteen days until 4 weeks after
      intervention new mineralization processes could be observed. New bone grew from
      the borders into the defect. In the 2D study, bone apposition changed
      significantly from the beginning to week 8 (0.08 to 0.74 mm) as well as the 3D
      bone gain (0.05 % to 29.67 %) in t-test statistical evaluation. For development
      of the bone volume inside the defect linear as well as exponential regression
      analysis revealed a statistically significant connection. CONCLUSIONS: This study
      quantified the amount of newly grown bone during osseous regeneration. We could
      show that the mandible itself provides regenerative capacity without any intact
      periosteum.

PMID- 24577631
TI  - Serum uric acid level is associated with the prevalence but not with survival of
      amyotrophic lateral sclerosis in a Chinese population.
AB  - Oxidative stress is involved in the pathogenesis of amyotrophic lateral sclerosis
      (ALS). Serum uric acid (UA) has anti-oxidative effect. To clarify the
      associations between UA and sporadic ALS (SALS) in Chinese population. A total of
      512 SALS patients and 501 age- and gender- matched healthy controls were
      included, with fasting serum UA evaluated. The ALS functional rating scale
      Revised was used to assess disease severity, and the mean change of ALSFRS-R per
      month (?ALS-FRS-R/m) to assess its progression. Four hundred forty-five patients
      were followed up. Survival and progression were estimated according to quartiles
      and gender-specific quartiles of UA. The mean age of SALS patients was 53.3 +/-
      11.7 years. UA level of SALS was significantly lower than controls (p = 0.001).
      Male SALS had higher UA than female (p = 0.001). The occurrence of SALS was
      increased in the lowest, second and third quartiles compared with the highest
      quartile (p = 0.001). In the gender-specific analysis, increased occurrence was
      found in the lowest and second quartiles compared with third and fourth quartiles
      in both males and females SALS (p(f) = 0.001 and p(m) < 0.05). No correlation was
      found between ?ALS-FRS-R/m and UA (p > 0.05), nor between SALS survival and UA.
      SALS patients have low level of serum UA than controls. Low level of uric acid
      may be associated with increased occurrence of SALS in Chinese population. Uric
      acid level may not contribute to the survival or progression of SALS.

PMID- 24577629
TI  - Posterior maxillary implants inserted with bicortical anchorage and placed in
      immediate function for partial or complete edentulous rehabilitations. A
      retrospective clinical study with a median follow-up of 7 years.
AB  - PURPOSE: The aim of this study was to report the outcome of posterior maxillary
      implants inserted with "bicortical anchorage" in medium or low-density bone and
      placed in immediate function for the rehabilitation of patients with partial or
      complete edentulism. METHODS: Eighty-eight patients (32 males and 56 females,
      mean age = 54 years; range 28-78 years) were included from October 1999 to
      November 2008, and followed between 6 months and 13 years (median of 7 years). A
      total of 124 posterior maxillary implants were inserted with bicortical anchorage
      (engaging the cortical plates of the maxillary crest along with that of either
      the sinus or nasal cavities) as follows: MkII (n = 1), MkIII (n = 6), MkIV (n =
      18), and NobelSpeedy Groovy (n = 99); (Nobel Biocare AB). Implants were evaluated
      on the basis of survival, marginal bone levels, and complications (mechanical and
      biological). RESULTS: Eleven patients dropped out of the study (12.5 %). Four
      implants were lost in four patients who underwent complete edentulous
      rehabilitations, yielding a cumulative survival rate of 94.2 % after a median
      follow-up of 7 years. The survival rate for the prostheses was 100 %. The
      marginal bone levels were on average 1.56 mm (standard deviation of 0.87 mm),
      after 5-years of follow-up. Biological complications occurred with 17 implants in
      17 patients. Mechanical complications occurred in 49/88 patients. Thirty of these
      49 patients were heavy bruxers. CONCLUSIONS: Within the limitations of this
      study, fixed prosthetic rehabilitations for partial and complete edentulism
      supported by implants in the posterior maxilla which are inserted with bicortical
      anchorage and placed in immediate function is a viable concept on long-term
      follow-up. Nevertheless, controlling the occlusion is mandatory in order to
      decrease the likelihood of mechanical complications.

PMID- 24577634
TI  - Supramolecular hydrogen-bonding assembly of silanediols with bifunctional
      heterocycles.
AB  - X-ray crystallography showcases the distinct self-association and hydrogen
      bonding patterns of organic silanediols, R2Si(OH)2, with bifunctional
      heterocycles for supramolecular assembly. Diffusion-ordered spectroscopy (DOSY)
      studies identify the dominant hydrogen-bonding patterns and structures in
      solution, which correlate with solid-state patterns at high concentrations. 

PMID- 24577632
TI  - Adult neurogenesis in the African giant rat (Cricetomysgambianus, waterhouse).
AB  - African giant rats (AGR) are large nocturnal rodents with well-developed
      olfactory abilities uniquely linked to cognition. The post natal proliferation of
      neurons (adult neurogenesis), is thought to play an important role in spatial
      memory and learning. Eighteen brains of the African giant rats (Cricetomys
      gambianus, Waterhouse) belonging to three age groups (neonates n = 6, juveniles n
      = 6 and adults n = 6) were examined by immunohistochemistry, using antibodies for
      proliferating cells (Ki-67), and immature neurons (Doublecortin, DCX). Mean brain
      weights were 0.40 +/- 0.00 g; 4.48 +/- 0.43 g and 5.48 +/- 0.56 g for neonate,
      juvenile and adult brains respectively. Our results show positive cell
      proliferation in the subventricular (SVZ) zone of the lateral ventricle and in
      the dentate gyrus (DG) of the hippocampus but at low levels in adults compared to
      juveniles. Estimate of the mean total proliferative Ki-67 positive cells in the
      SVZ and DG in the neonates was 21145 +/- 8395, and 11800 +/- 1230; brains from
      juvenile AGRs, 45530 +/- 13950 and 12480 +/- 7860 and from adult brains, (6880 +/
      340 and 1130 +/- 150) respectively. Juvenile AGR in particular, stained
      positively in potential sites such as the piriform and somatosensory cortices,
      striatum and cerebellum. This intensity of the proliferating cells within the
      dentate gyrus in the juvenile and adult brains could be associated with a role in
      the cognitive functions of landmine detection and tuberculosis diagnosis after
      olfactory training of the African giant rat. The juvenile rats are proposed as
      the most suited for experimental research and olfactory training.

PMID- 24577633
TI  - Effects of hyperammonemia on brain energy metabolism: controversial findings in
      vivo and in vitro.
AB  - The literature related to the effects of elevated plasma ammonia levels on brain
      energy metabolism is abundant, but heterogeneous in terms of the conclusions.
      Thus, some studies claim that ammonia has a direct, inhibitory effect on energy
      metabolism whereas others find no such correlation. In this review, we discuss
      both recent and older literature related to this controversial topic. We find
      that it has been consistently reported that hepatic encephalopathy and
      concomitant hyperammonemia lead to reduced cerebral oxygen consumption. However,
      this may not be directly linked to an effect of ammonia but related to the fact
      that hepatic encephalopathy is always associated with reduced brain activity, a
      condition clearly characterized by a decreased CMRO2. Whether this may be related
      to changes in GABAergic function remains to be elucidated. 

PMID- 24577640
TI  - Anterosuperior diverticula of the right ventricle: morphological spectrum and
      long-term outcome of a distinct cardiac anomaly.
AB  - Right-ventricular diverticula (RVD), although rare, have particular
      characteristics. Our study describes the morphology of anterosuperior diverticula
      of the right ventricle (RV) and patient outcome for this anomaly. Retrospective
      analysis was performed on all patients with anterosuperior RVD diagnosed in two
      tertiary referral centres. From January 1982 to December 2012, five patients were
      diagnosed with anterosuperior RVD (median 4 months). Four patients had
      perimembranous ventricular septal defects (VSDs) with no clinical symptoms
      related to RVD. Communication of the RVD with the RV was located either close to
      the VSD (two patients) or in the anterior free wall of the RV opposite the VSD
      (two patients). In the remaining patient, the diverticulum was connected with the
      left ventricle (LV) by a tunnel-like structure originating from the left
      ventricular outflow tract; the RVD communicated with the RV by way of a
      restrictive opening. Four patients underwent surgical repair including patch
      closure of the VSD (one patient) and patch closure of the VSD through an incision
      of the RVD followed by plication of the diverticulum or closure of its
      communication with the RV (three patients). All patients remained asymptomatic
      during a median follow-up of 14.8 years. Anterosuperior RVD is a specific
      congenital cardiovascular anomaly frequently associated with additional
      congenital heart disease. There are significant variations in how the RVD
      communicates with the RV with each requiring a different surgical repair
      strategy. According to the experience in our small cohort, the long-term
      prognosis of patients with anterosuperior RVD appears excellent after surgical
      correction of associated congenital heart disease. 

PMID- 24577641
TI  - Pharmacokinetics of sulfamonomethoxine in tongue sole (Cynoglossus semilaevis)
      after intravenous and oral administration.
AB  - The pharmacokinetic profiles of sulfamonomethoxine (SMM) were investigated in
      flatfish tongue soles in the present study. After a single injection of SMM (40
      mg/kg BW) to caudal vein of tongue sole at 20  degrees C, plasma drug
      concentration versus time data were best fitted to a three-compartment model,
      characterized with 0.2, 5.7, and 80.4 h for the half-life (t 1/2) of fast
      distribution, slow distribution, and elimination, respectively. The apparent
      volume of distribution was 0.1 L/kg, and the body clearance was 0.03 L/h/kg.
      After oral administration of SMM (200 mg/kg BW) to tongue soles at 20  degrees C,
      plasma drug concentrations were best fitted to a two-compartment model, of which
      the mean half-life of absorption (t 1/2ka) and elimination (t 1/2beta ) were 1.7
      and 95.7 h, respectively. The maximal absorption concentration (C max) was
      estimated as 58 mg/L at 2.5 h, and the mean systemic bioavailability (F) was 39.5
      % in tongue soles after oral administration. 

PMID- 24577642
TI  - Synthesis of magneto-sensitive iron-containing nanoparticles by yeasts.
AB  - Industrial production of magneto-sensitive nanoparticles, which can be used in
      the production of target drug delivery carriers, is a subject of interest for
      biotechnology and microbiology. Synthesis of these nanoparticles by
      microorganisms has been described only for bacterial species. At the same time,
      it is well known that yeasts can form various metal-containing nanoparticles
      used, for instance, in semiconductors, etc. This paper describes the first
      results of the biosynthesis of magneto-sensitive nanoparticles by yeasts. The
      organisms we used-Saccharomyces cerevisiae and Cryptococcus humicola-represented
      two different genera. Magneto-sensitive nanoparticles were synthesized at room
      temperature in bench-scale experiments. The study included transmission electron
      microscopy of the yeast cells and their energy dispersive spectrum analyses and
      revealed the presence of iron-containing nanoparticles. Both yeast cultures
      synthesized nanoparticles at high concentrations of dissolved iron. Electron
      microscopy showed that nanoparticles were associated mainly with the yeast cell
      wall. Formation of magneto-sensitive nanoparticles was studied under conditions
      of applied magnetic fields; a possible stimulating role of magnetic field is
      suggested. On the whole, the paper reports a novel approach to green biosynthesis
      of magneto-sensitive nanoparticles. 

PMID- 24577639
TI  - Cadmium-induced ototoxicity in rat cochlear organotypic cultures.
AB  - Cadmium (Cd), a widely used industrial metal, is extremely nephrotoxic and
      neurotoxic; however, its effects on the peripheral auditory system are poorly
      understood. To evaluate the ototoxicity of Cd, we treated cochlear organotypic
      cultures from postnatal day 3 rats with Cd concentrations from 10 to 500 MUM for
      24 or 48 h. Afterward, we evaluated the degree of damage to hair cells, auditory
      nerve fibers, and spiral ganglion neurons. Damage to the hair cells, auditory
      nerve fibers, and spiral ganglion neurons systematically increased in a dose and
      time-dependent manner. Exposure to Cd concentrations of 10 MUM for 24 and 48 h
      resulted in minor inner and outer hair cell loss in the basal third of the
      cochlea. As Cd concentrations increased, toxicity spread toward the apex, also in
      a time-dependent manner. Treatment with 100 MUM Cd for 48 h resulted in
      substantial (>30 %) hair cell loss over the entire cochlea. Cd was also toxic to
      auditory nerve fibers and spiral ganglion neurons; 100 MUM of Cd for 24 h or 10
      MUM of Cd for 48 h resulted in considerable damage to auditory nerve fibers and
      spiral ganglion neurons. These findings are the first to demonstrate that Cd can
      cause significant lesions to peripheral auditory nerve fibers, spiral ganglion
      neurons, and sensory hair cells in organotypic cultures from postnatal cochleae.

PMID- 24577643
TI  - Do field walking tests produce similar cardiopulmonary demands to an incremental
      treadmill test in obese individuals with treated OSA?
AB  - BACKGROUND: Cardiorespiratory fitness, assessed during cardiopulmonary exercise
      tests by peak oxygen uptake (Vo2pk), is an independent predictor of mortality in
      obesity. We investigated whether Vo2pk and systemic responses measured during
      field walking tests were similar to those measured during an incremental
      treadmill test (ITMT) in obese individuals with treated OSA. METHODS: Individuals
      with treated OSA and a BMI > 30 kg/m2 were recruited. Participants completed an
      ITMT, two 6-min walk tests (6MWTs), and two incremental shuttle walk tests
      (ISWTs) on three separate days in a randomized order. Expired gas analysis was
      performed during all tests. RESULTS: The study was completed by 16 patients (nine
      men) (mean [SD] age, 58 [12] y; BMI, 36.1 [7.6] kg/m2). There was no difference
      (P = .27) in Vo2pk assessed by the ITMT and the ISWT (2,266 [478] and 2,017 [561]
      mL/min, respectively). The Vo2pk measured by the 6MWT (1,778 [360] mL/min) was
      lower than that measured by the ITMT (P < .01). The limits of agreement for Vo2pk
      between the ISWT and the ITM were +/- 730 mL/min. Cardiorespiratory responses
      during the ISWT and the ITMT reflected a graded response to a peak, whereas the
      6MWT demonstrated a rapid rise to a plateau. CONCLUSIONS: The ISWT can be used
      instead of an ITMT and in preference to the 6MWT to assess cardiorespiratory
      fitness for a cohort of obese people with treated OSA. However, the imprecision
      of the agreement in Vo2pk between the ITMT and ISWT means they cannot be used
      interchangeably in an individual. TRIAL REGISTRY: ClinicalTrials.gov; No.:
      NCT01930513; www.clinicaltrials.gov.

PMID- 24577644
TI  - Elevated CO2, litter chemistry, and decomposition: a synthesis.
AB  - The results of published and unpublished experiments investigating the impacts of
      elevated [CO2] on the chemistry of leaf litter and decomposition of plant tissues
      are summarized. The data do not support the hypothesis that changes in leaf
      litter chemistry often associated with growing plants under elevated [CO2] have
      an impact on decomposition processes. A meta-analysis of data from naturally
      senesced leaves in field experiments showed that the nitrogen (N) concentration
      in leaf litter was 7.1% lower in elevated [CO2] compared to that in ambient
      [CO2]. This statistically significant difference was: (1) usually not significant
      in individual experiments, (2) much less than that often observed in green
      leaves, and (3) less in leaves with an N concentration indicative of complete N
      resorption. Under ideal conditions, the efficiency with which N is resorbed
      during leaf senescence was found not to be altered by CO2 enrichment, but other
      environmental influences on resorption inevitably increase the variability in
      litter N concentration. Nevertheless, the small but consistent decline in leaf
      litter N concentration in many experiments, coupled with a 6.5% increase in
      lignin concentration, would be predicted to result in a slower decomposition rate
      in CO2-enriched litter. However, across the assembled data base, neither mass
      loss nor respiration rates from litter produced in elevated [CO2] showed any
      consistent pattern or differences from litter grown in ambient [CO2]. The effects
      of [CO2] on litter chemistry or decomposition were usually smallest under
      experimental conditions similar to natural field conditions, including open-field
      exposure, plants free-rooted in the ground, and complete senescence. It is
      concluded that any changes in decomposition rates resulting from exposure of
      plants to elevated [CO2] are small when compared to other potential impacts of
      elevated [CO2] on carbon and N cycling. Reasons for experimental differences are
      considered, and recommendations for the design and execution of decomposition
      experiments using materials from CO2-enrichment experiments are outlined. 

PMID- 24577645
TI  - Mixing models in analyses of diet using multiple stable isotopes: a critique.

PMID- 24577646
TI  - Uncertainty in source partitioning using stable isotopes.
AB  - Stable isotope analyses are often used to quantify the contribution of multiple
      sources to a mixture, such as proportions of food sources in an animal's diet, or
      C3 and C4 plant inputs to soil organic carbon. Linear mixing models can be used
      to partition two sources with a single isotopic signature (e.g., delta(13)C) or
      three sources with a second isotopic signature (e.g., delta(15)N). Although
      variability of source and mixture signatures is often reported, confidence
      interval calculations for source proportions typically use only the mixture
      variability. We provide examples showing that omission of source variability can
      lead to underestimation of the variability of source proportion estimates. For
      both two- and three-source mixing models, we present formulas for calculating
      variances, standard errors (SE), and confidence intervals for source proportion
      estimates that account for the observed variability in the isotopic signatures
      for the sources as well as the mixture. We then performed sensitivity analyses to
      assess the relative importance of: (1) the isotopic signature difference between
      the sources, (2) isotopic signature standard deviations (SD) in the source and
      mixture populations, (3) sample size, (4) analytical SD, and (5) the evenness of
      the source proportions, for determining the variability (SE) of source proportion
      estimates. The proportion SEs varied inversely with the signature difference
      between sources, so doubling the source difference from 20/00 to 40/00 reduced
      the SEs by half. Source and mixture signature SDs had a substantial linear effect
      on source proportion SEs. However, the population variability of the sources and
      the mixture are fixed and the sampling error component can be changed only by
      increasing sample size. Source proportion SEs varied inversely with the square
      root of sample size, so an increase from 1 to 4 samples per population cut the SE
      in half. Analytical SD had little effect over the range examined since it was
      generally substantially smaller than the population SDs. Proportion SEs were
      minimized when sources were evenly divided, but increased only slightly as the
      proportions varied. The variance formulas provided will enable quantification of
      the precision of source proportion estimates. Graphs are provided to allow rapid
      assessment of possible combinations of source differences and source and mixture
      population SDs that will allow source proportion estimates with desired
      precision. In addition, an Excel spreadsheet to perform the calculations for the
      source proportions and their variances, SEs, and 95% confidence intervals for the
      two-source and three-source mixing models can be accessed at
      http://www.epa.gov/wed/pages/models.htm. 

PMID- 24577647
TI  - Mixing models in analyses of diet using multiple stable isotopes: a response.

PMID- 24577648
TI  - Branching responses of a plagiotropic clonal herb to localised incidence of light
      simulating that reflected from vegetation.
AB  - Plants sense the presence of neighbouring vegetation through phytochrome
      photoreceptors perceiving a lowered red to far-red ratio (R:FR) of light
      reflected from such vegetation. We hypothesised that it would be advantageous for
      the grassland clonal herb, Trifolium repens, to have an inhibitory branching
      response to perception by leaves of light reflected from neighbouring vegetation
      (i.e. light with lowered R:FR ratio) but have no response to interception of such
      light by the plagiotropic stem. We tested whether photoreception of reflected
      light by plagiotropic stems resulted in a different branching response to
      photoreception by leaves and whether leaf ontogeny influenced the response. To
      simulate light reflected from vegetation, FR light-emitting-diodes were used to
      supplement controlled environment room light so that the R:FR ratio, but not the
      photosynthetic photon fluence rate, of light incident at the stem or leaf of a
      phytomer of T. repens was lowered from 1.20 to 0.25. The plagiotropic stems were
      unresponsive to light simulating that reflected from vegetation. This response
      differs from that of stems of orthotropic species, indicating that plagiotropic
      stems have evolved an organ-specific photobiology. Treatment of the mature leaf
      with light of lowered FR ratio reduced phytomer production only of the branch in
      the axil of the treated leaf. Similar treatment of the immature leaf retarded, in
      addition, branching at basal phytomers on the same side of the primary stem axis.
      Thus the response to light simulating that reflected from neighbouring vegetation
      depended upon whether the light was incident at the stem or the leaf and on the
      stage of leaf development. We argue that such responses improve the performance
      and fitness of T. repens within grassland habitats by allowing axillary buds on
      plagiotropic stems to branch freely when stems are in receipt of light reflected
      from vegetation while leaves are in full light. 

PMID- 24577649
TI  - Antler length of yearling red deer is determined by population density, weather
      and early life-history.
AB  - In red deer, yearling antler length is a largely nutrition-mediated phenotypic
      character, and is therefore sometimes used as an indirect estimate of range
      quality and population condition. However, the parameters affecting yearling
      antler length have been little studied. We analyse the contributions of density,
      weather and maternal effects on yearling antler length of 581 individual stags
      born 1970-1996 on the Isle of Rum (Scotland). We show that antler length is a
      good measure of yearling condition: the probability of overwinter survival in
      yearlings that developed antlers was 3 times higher than for yearlings that did
      not develop antlers, and yearling antler length was correlated with the number of
      antler points the following year. Between years, variation in yearling antler
      length was best explained by variation in red deer density and June temperature
      at 12 months of age. Both of these variables were negatively correlated with
      antler length, and most likely this effect is due to changes in nutrient
      availability. Population density affects biomass availability for the individual,
      while low temperatures in early summer prolong the availability of high forage
      quality. At the individual level, antler length increased with birth weight and
      decreased with birth date, reflecting the persistent and pervasive influence of
      conditions in early life. 

PMID- 24577650
TI  - Regulation of leaf life-span and nutrient-use efficiency of Metrosideros
      polymorpha trees at two extremes of a long chronosequence in Hawaii.
AB  - Leaf traits related to life-span and nutrient-use efficiency were studied in the
      dominant Hawaiian tree species, Metrosideros polymorpha, at both ends of a
      natural fertility gradient, from young, nitrogen-poor soils to older, phosphorus
      poor soils. The main objective of this study was to understand how nutrient
      limitations affect leaf-level attributes that ultimately play a mechanistic role
      in regulating whole-ecosystem function. Different types of adjustments to removal
      of nutrient limitation by long-term fertilization (9-15 years) with nitrogen (N),
      phosphorus (P), and a combined treatment of N plus P were observed at each site.
      Nitrogen fertilization at the young, mostly N-limited site did not significantly
      affect net CO2 assimilation (A), foliar N content, or N resorption. The primary
      response to N fertilization was a decrease in average leaf life span to
      approximately 553 days compared with 898 days in the control plot. Significantly
      shorter average leaf life-span coupled with constant A and foliar N content
      resulted in reduced integrated photosynthetic nitrogen-use efficiency (PNUE: A
      summed over the life-span of a leaf divided by foliar N) in the fertilized plots.
      In contrast, removal of nutrient limitations at the old, mostly P-limited site
      resulted in increased A, and increased foliar P concentration which also resulted
      in reduced integrated photosynthetic phosphorus-use efficiency (PPUE). P
      resorption was also reduced at this site, yet leaf life-span remained constant.
      When results from both sites and all treatments were combined, statistically
      significant relationships between leaf life-span, and A, leaf mass per area
      (LMA), and the cost of leaf construction per unit carbon gain (cost of
      construction determined by combustion of leaf samples divided by A) were found.
      As leaf life-span increased, A decreased asymptotically, and LMA and the carbon
      cost per carbon gain increased linearly. It appears that the balance between leaf
      carbon cost and carbon uptake is a major determinant of leaf longevity in M.
      polymorpha despite contrasting responses to removal of N and P limitations by
      long-term fertilization. Removal of the main nutrient limitations at both sites
      also resulted in reduced integrated nutrient use efficiency. However, the
      regulatory mechanisms were different depending on the site limitations: a shorter
      leaf life-span in the young, N-limited site and substantially higher foliar P
      concentration in the P-fertilized plots at the old, P-limited site. 

PMID- 24577651
TI  - Nutrient composition of the prey's diet affects growth and survivorship of a
      generalist predator.
AB  - It is well known that secondary chemicals produced at one trophic level may
      affect organisms at subsequent levels of the food chain. Effects of nutrient
      supplements may also propagate through trophic levels, but the mechanisms here
      are less clear. We tested the hypothesis that predators can be affected by the
      nutrient composition of the prey's food. Wolf spider (Pardosa amentata)
      hatchlings were raised ad libitum on fruit flies (Drosophila melanogaster) that
      were cultured in poor basic medium with additions of different nutrients. These
      additions strongly affected the performance of the spiders. Growth rates
      increased when additions consisted of 19 different amino acids or fatty
      acids+cholesterol or commercial dogfood. Survival increased in spiders reared on
      fruit flies from cultures containing 19 amino acids or methionine or dogfood. The
      addition of dogfood increased spider growth and survival more significantly than
      the addition of any single nutrient group alone. Adult female flies from the
      dogfood culture were significantly heavier than females from the basic culture.
      The nutrients added to the fruit fly media were thus able to create biological
      effects at both the second and the third trophic levels. To test whether
      nutrients passed to the predators through the gut content of the prey, we
      included a treatment where the spiders were fed flies that had been starved for
      48 h in order to empty their guts. Gut emptying of the flies did not reduce the
      positive effects of the enriched fruit fly media, i.e. the nutritional benefits
      were not due to nutrients that passed directly through the guts of the flies.
      Since the nutrients added to the fruit fly media were separated from the spiders
      that benefited from them by two trophic transformations, this phenomenon was a
      true tritrophic interaction. 

PMID- 24577652
TI  - Leaf uptake of nitrogen dioxide (NO2) in a tropical wet forest: implications for
      tropospheric chemistry.
AB  - Tropical forest soils are known to emit large amounts of reactive nitrogen oxide
      compounds, often referred to collectively as NOy (NOy = NO + NO2 + HNO3 + organic
      nitrates). Plants are known to assimilate and emit NOy and it is therefore likely
      that plant canopies affect the atmospheric concentration of reactive nitrogen
      compounds by assimilating or emitting some fraction of the soil-emitted NOy. It
      is crucial to understand the magnitude of the canopy effects and the primary
      environmental and physiological controls over NOy exchange in order to accurately
      quantify regional NOy inventories and parameterize models of tropospheric
      photochemistry. In this study we focused on nitrogen dioxide (NO2), which is the
      component of NOy that most directly catalyzes the chemistry of O3 dynamics, one
      of the most abundant oxidative species in the troposphere, and which has been
      reported as the NOy species that is most readily exchanged between plants and the
      atmosphere. Leaf chamber measurements of NO2 flux were measured in 25 tree
      species growing in a wet tropical forest in the Republic of Panama. NO2 was
      emitted to the atmosphere at ambient NO2 concentrations below 0.53-1.60 ppbv (the
      NO2 compensation point) depending on species, with the highest rate of emission
      being 50 pmol m(-2) s(-1) at <0.1 ppbv. NO2 was assimilated by leaves at ambient
      NO2 concentrations above the compensation point, with the maximum observed uptake
      rate being 1,550 pmol m(-2) s(-1) at 5 ppbv. No seasonal variation in leaf NO2
      flux was observed in this study and leaf emission and uptake appeared to be
      primarily controlled by leaf nitrogen and stomatal conductance, respectively.
      When scaled to the entire canopy, soil NO emission rates to the atmosphere were
      estimated to be maximally altered +/-19% by the overlying canopy. 

PMID- 24577653
TI  - Food stress and predator-induced stress shape developmental performance in a
      damselfly.
AB  - I studied effects of stress factors like food shortage, non-lethal predator
      presence and autotomy on survival and larval performance (growth rate,
      development rate and developmental stability) of larvae of the damselfly Lestes
      sponsa. In a laboratory experiment, larvae were raised during their last two
      instars at two food levels (high or low) crossed with two levels of autotomy
      (caudal lamellae present or absent). These treatments were nested within three
      levels of predation risk (Aeshna cyanea absent, Chironomus-fed caged Aeshna or
      Lestes-fed caged Aeshna). The diet of the predator had no effects. The low food
      level and the presence of Aeshna independently increased mortality rates of L.
      sponsa larvae. The low food level, presence of a caged Aeshna and autotomy all
      independently reduced growth rate (mass and body size at day 40) and wing size at
      emergence, and the first two stress factors also reduced development rate.
      Regardless of predator presence and autotomy, all damselfly larvae consumed the
      food available. This indicated that the predator-induced stress effects were not
      due to reduced food uptake, but probably reflected lowered assimilation
      efficiency and/or a higher metabolic rate. Besides a low food level, the presence
      of caged Aeshna predator larvae and autotomy also increased hind wing asymmetry.
      This result demonstrated that predator-induced stress may reduce developmental
      stability in the prey. 

PMID- 24577654
TI  - Birthdate, mass and survival in mountain goat kids: effects of maternal
      characteristics and forage quality.
AB  - In temperate environments, early-born ungulates may enjoy a longer growth period
      before winter, and so attain a higher body mass and an increased probability of
      survival compared to late-born ones. We assessed the effects of maternal
      characteristics, forage quality and population density on kid birthdate, mass and
      survival in a population of marked mountain goats (Oreamnos americanus) in
      Alberta. The duration and timing of the birth season were similar in all years.
      Births were highly synchronised: 80% of kids were born within 2 weeks of the
      first birth. Maternal age, maternal social rank and density did not affect kid
      birthdate or mass. Previous breeding experience was not related to kid birthdate,
      but kids born to pluriparous mothers were heavier during summer than kids born to
      primiparous mothers. Male and female kids had similar mass and accumulated mass
      linearly during summer. Early-born kids were heavier than late-born kids. Faecal
      crude protein (FCP) in late spring and maternal mass were positively related to
      kid mass. Survival to weaning appeared higher for males (90%) than for females
      (78%), but survival to 1 year was 65% for both sexes. FCP in late spring,
      density, birthdate and mass did not affect kid survival to weaning in either sex.
      Survival to 1 year increased with FCP in late spring for females, but not for
      males. Survival to 1 year was independent of birthdate for both sexes, but heavy
      females survived better than light ones. Multiple logistic regression revealed a
      positive effect of mass on survival to 1 year when the sexes were pooled. Our
      results suggest that mountain goats are constrained to give birth in a short
      birth season synchronised with forage productivity. 

PMID- 24577655
TI  - Long-distance pollinator flights and pollen dispersal between populations of
      Delphinium nuttallianum.
AB  - Spatial processes in pollination biology are poorly understood, especially at
      levels above that of the local population. For example, little is known about how
      pollinators and pollen move among populations, although there is evidence that
      such movement can exceed what is predicted from intrapopulational movement. We
      explored pollination success in experimental isolates of the bumblebee- and
      hummingbird-pollinated wildflower Delphinium nuttallianum. We established a total
      of 15 arrays of potted plants isolated by 50-400 m from ten natural "source"
      populations, as well as control arrays embedded within each source. Flowers on
      potted plants were emasculated, so any pollen received could be assumed to come
      from source populations. A total of 69 h of observation suggested that
      pollinators were somewhat less abundant in isolates than in controls, but visited
      more plants and flowers once within an isolate. Consistent with this, 82.1% of
      all flowers in isolated arrays received pollen, versus 87.7% in controls. Mean
      receipt was more than 100 pollen grains per flower in most arrays, and seed set
      in isolates and controls respectively averaged 69.8% and 74.3% of ovules.
      Furthermore, pollen receipt in isolates declined relatively slowly with distance
      from the source. We conclude that pollinators of D. nuttallianum often will fly
      up to 400 m among populations, and that substantial pollination ensues. Thus
      isolated populations of this species often belong to metapopulations in terms of
      pollen dispersal, with important consequences for genetic differentiation, and
      potential implications for the management of endangered plant species. 

PMID- 24577656
TI  - Host-plant mediated effects of root herbivory on insect seed predators and their
      parasitoids.
AB  - The effects of root herbivory on a tephritid seed predator (Terellia ruficauda)
      and its parasitoids were investigated. Soil fauna were manipulated by insecticide
      treatment; host plant (Cirsium palustre) phenology and the oviposition behaviour
      of both tephritid and parasitoids (Pteromalus elevatus and Torymus chloromerus)
      recorded. Although insecticide-treated (and hence reduced root herbivory) plants
      had larger flowerheads, population abundances of both tephritids and parasitoids
      were greater on thistle plants subjected to root herbivory. Percentage parasitism
      was similar in both treatments. Root herbivory is thought to enhance the nutrient
      quality of plants and this may have resulted in the tephritid preferentially
      feeding on thistles whose roots had been attacked. Parasitoids on these plants
      were probably affected by a combination of increased plant attractivity (as for
      the tephritids), smaller flowerheads aiding ovipositor entry and more tephritid
      hosts being present. This is the first study to show that root herbivores,
      through plant-mediated interactions, can affect seed herbivores and also, albeit
      indirectly through the host, natural enemy trophic levels. 

PMID- 24577657
TI  - Leaf abscission phenology of a scrub oak: consequences for growth and
      survivorship of a leaf mining beetle.
AB  - Brachys tessellatus is a leaf-mining beetle that attacks Quercus laevis (turkey
      oak), a deciduous scrub oak in the fall line Sandhills of the southeastern United
      States. This oak species varies substantially in leaf abscission phenology. In
      the fall of 1994 we examined leaf abscission patterns at three sites in central
      South Carolina and found that leaves containing active miners abscised earlier
      than leaves without active miners. To quantify the effect of leaf abscission
      phenology on the survivorship and body size of leaf miners within the abscised
      leaves, we marked naturally and manually abscised leaves, left leaves on the
      ground to over-winter, and then collected leaves before beetles emerged the
      following spring. We found that beetles inside leaves that were abscised early in
      the season were more likely to be killed by predators, and that they produced
      smaller pupae than beetles within leaves abscised later in the season. We also
      evaluated the relationship between adult beetle body size and fecundity; body
      size of B. tessellatus is positively correlated with lifetime fecundity and daily
      oviposition rate indicating that effects of leaf-abscission phenology on beetle
      body size likely translate into effects on beetle fitness. We discuss how B.
      tessellatus has adapted to variation of leaf abscission phenology of oaks by
      evolving developmental plasticity that permits successful completion of larval
      development over a range of season lengths. 

PMID- 24577658
TI  - Herbivory, litter and soil disturbance as determinants of vegetation dynamics
      during early old-field succession under set-aside.
AB  - Early-successional old fields are a major component of the European landscape.
      While a range of factors governing vegetation development in old fields has been
      identified, empirical and theoretical studies have tended to concentrate on plant
      competition as the dominant driving force behind succession. We studied the
      influence of three little researched, yet inter-related, factors on the early
      stages of an old-field succession: litter cover, soil disturbance and herbivory.
      Physical and chemical techniques were used to exclude large vertebrates and
      insects from experimental plots. These treatments had little effect on plant
      recruitment. A litter-removal experiment, nested within the exclusion treatments,
      revealed a significant inhibition of forb seedling germination by litter cover.
      However, the majority of seedlings died during the first month following
      emergence, whether or not litter was removed. A second experiment, involving the
      factorial combination of mollusc exclusion and soil disturbance, revealed that
      the response to disturbance was dependent on life-history characteristics of the
      plants. However, the dominant factor regulating community composition was
      seedling herbivory by molluscs. Molluscs caused high rates of forb seedling
      mortality and promoted the transition from a forb-dominated, to a grass-dominated
      community. Herbivory is often assumed to influence plant community dynamics
      through effects on competitive interactions. However, direct effects of
      herbivory, on the survival of seedlings, may be a significant factor structuring
      plant communities in ruderal, or other annual dominated systems. 

PMID- 24577659
TI  - Causes and consequences of floral damage in Aconitum lycoctonum at high and low
      elevations in Switzerland.
AB  - The outcomes of interactions among plants and the insects that use their flowers
      are likely to vary among the physical environments and the communities in which
      they grow. In this study we quantified floral damage of Aconitum lycoctonum in
      high (>2000 m) and low (c. 500 m) elevation populations in Switzerland. At high
      elevation, floral damage was frequent and was caused by nectar-robbing short
      tongued bumblebees. Nectar robbers make a hole in the flower when they collect
      nectar. A nectar robber exclusion experiment showed that nectar robbery by short
      tongued bumblebees had no effect on the female reproductive success of plants;
      robbing bees rarely damaged the nectaries, and damage to the petals probably does
      not decrease flower longevity. In addition, nectar robbers tended to collect
      pollen during about 10% of their visits. Thus, these bees may act as low
      efficiency pollinators and may, at times, be mutualistic associates. At low
      elevation, the holes in the flowers were caused by beetles (Meligethes
      viridescens) and not by short-tongued bumblebees. The beetles eat pollen and
      might also consume nectar. Since the beetles gain access to pollen and nectar by
      entering the flower through its opening, and later chew holes while foraging on
      floral tissue, the beetles are pollen eaters rather than nectar robbers. Overall,
      our results show that not all floral damage is caused by nectar robbers and that
      there can be strong altitudinal variation in the causes and consequences of
      floral damage. 

PMID- 24577660
TI  - Herbivore-induced ethylene burst reduces fitness costs of jasmonate- and oral
      secretion-induced defenses in Nicotiana attenuata.
AB  - Specialist herbivores are known to alter their host's wound-induced responses but
      the beneficiaries of these alterations are unknown. Nicotiana attenuata plants
      release a burst of ethylene specifically in response to feeding by Manduca sexta
      larvae, which is known to suppress wound- and methyl jasmonate (MeJA)-inducible
      nicotine accumulation. The ethylene burst may be a mechanism by which M. sexta
      larvae feed "stealthily" on their host plants or, alternatively, it may allow the
      plant to optimize its defense response against this specialist herbivore by
      reducing costs of induction. We examined the impact of the ethylene burst on
      defense-related fitness costs that are readily observed when plants are treated
      with MeJA and grown in competition with untreated plants. We elicited nicotine
      induction (with MeJA), the ethylene burst (with the ethylene releasing compound,
      ethephon) and inhibited the plant's ability to perceive ethylene (with
      applications of an antagonist of ethylene receptors, 1-methylcyclopropene, 1
      MCP). By simultaneously applying MeJA and ethephon we mimicked the plant's
      hormonal response to larval attack. We hypothesized that if the ethylene burst
      benefited the plant, the fitness costs of MeJA induction should be reduced by
      ethephon and restored if the plants were additionally treated with 1-MCP. In a
      second experiment, we applied larval oral secretion (OS) to elicit endogenous
      hormone production and predicted that the 1-MCP treatment should reduce the
      fitness of OS-treated plants. Our measures of plant fitness, namely the rate of
      stalk elongation and lifetime capsule production, supported these predictions. We
      conclude that the ethylene burst elicited by this specialist herbivore can reduce
      MeJA-induced fitness costs and increase the competitive strength of OS-treated
      plants. Suppressed nicotine production is likely to contribute to, but is not
      sufficient to explain, the observed fitness outcomes. The intensity of intra
      specific competition and herbivore attack will likely determine the adaptive
      value of the M. sexta-elicited ethylene response. 

PMID- 24577661
TI  - An interactive effect of simultaneous death of dwarf bamboo, canopy gap, and
      predatory rodents on beech regeneration.
AB  - To clarify the interactive effect of the simultaneous death of dwarf bamboo (Sasa
      kurilensis), forest canopy gap formation, and seed predators on beech (Fagus
      crenata) regeneration, we analyzed beech demography from seed fall until the end
      of the first growing season of seedlings in an old-growth forest near Lake
      Towada, northern Japan. The simultaneous death of S. kurilensis took place in
      1995. We established four types of sampling site differing in forest canopy
      conditions (closed or gap) and Sasa status (dead or alive). Beech seed survival
      and emergence ratio were both highest in gaps with dead Sasa (gap-dead), because
      rate of predation was lowest. Seedling survival during the first growing season
      was also highest in the gap-dead treatment, because of less predation and less
      damping off. As a result, even though density of seed fall was lowest in the gap
      dead treatment, the living seedling density there was highest at the end of the
      first growing season. Predation, which caused the greatest mortality during the
      seed and seedling stages, was significantly lower at both sites in gaps and sites
      with dead Sasa. This was probably due to changes in the behavior of rodents in
      response to the structure of the forest canopy and undergrowth. Both the death of
      Sasa and canopy gap formation allowed seedlings to avoid damping off because of
      the high light availability. The indirect effect of the simultaneous death of
      Sasa and canopy gap formation in reducing predation contributed more to beech
      regeneration than their direct effect in increasing light for the seedlings. 

PMID- 24577662
TI  - The influence of matrix habitat on Aphthona flea beetle immigration to leafy
      spurge patches.
AB  - Variation in movement ability by insects among different non-habitat (matrix)
      types may have important implications for both metapopulation dynamics and weed
      biocontrol practices. We used a mark-recapture experiment to explore the effects
      of two different matrix habitats (grass vs shrub) on the ability of two species
      of Aphthona (Chrysomelidae: Coleoptera) flea beetle to immigrate to patches of
      the invasive weed, leafy spurge. Using generalized linear models, we compared
      effects of the matrix habitat types, species and sex on observed immigration
      probabilities. Our analyses demonstrated that one species (A. nigriscutis) had a
      much higher immigration probability when moving through a grass-dominated matrix
      than a shrub-dominated matrix whereas immigration probabilities for the second
      species (A. lacertosa) were similar in both matrix habitats but significantly
      lower overall than for A. nigriscutis. Furthermore, A. nigriscutis females were
      more likely to immigrate to spurge patches embedded in a grass matrix than in
      shrub, whereas the opposite occurred for males. Our results suggest that
      metapopulation dynamics may be strongly affected by the type(s) of matrix habitat
      present on a landscape. These effects also suggest that release strategies for
      weed biocontrol should be tailored according to the structure of the landscape
      into which releases are planned. In addition, even closely related species can
      have significantly different movement abilities which will also affect release
      strategies. 

PMID- 24577663
TI  - Does the timing of litter inputs determine natural abundance of (13)C in soil
      organic matter? Insights from an African tiger bush ecosystem.
AB  - We investigated total primary production and natural abundance of (13)C in soil
      and plants in the landscape of tiger bush, Niger. Tiger bush is viewed as a
      natural cyclic succession of several types of vegetation (grasses, living trees
      and senescent vegetation) occurring over very small areas, on soils with similar
      chemical and physical characteristics. Under the pioneer front, production was
      130 g m(-2) year(-1) of which 23% came from C4 plants; under the thicket of
      mature trees, grass production was 190 g m(-2) year(-1) (all C3 grasses) and
      under senescent vegetation, 40 g m(-2) year(-1) of which 1.5% came from C4
      plants. Total above- and belowground primary production was estimated to be 890
      4880 g m(-2) year(-1) of which 0.4-0.5% was contributed by C4 plants. From 29 to
      45% of the soil organic carbon originated from C4 plants even though the
      contribution of C4 grasses to total primary production did not exceed 0.5%. We
      suggest that the order in which the different sources of organic matter entered
      the soil could lead to the overlabelling of soil organic matter with a C4 print.
      Because all C4 plants are grasses located in the pioneer front of tiger bush
      bands, their C4 organic matter enters the soil first and fixes onto clays. The C3
      organic matter enters the soil several years later and is also fixed by the clays
      but in a lower proportion. Therefore it is less protected from microbial activity
      and quickly decomposes. We postulate that the repetition of this pattern over
      many decades (incorporation of a pure C4 material to soil, followed by the
      incorporation of a C3-dominated material), leads to the overaccumulation of C4
      compounds on the most protective sites. 

PMID- 24577664
TI  - Neuroticism focuses attention: evidence from SSVEPs.
AB  - Neuroticism and negative affect have been associated with an increase in
      attentional investment and the greater processing of irrelevant stimuli. Previous
      research proposes the overinvestment of attention and a focused mental state as
      the mechanism of this effect. We investigated the neural correlates of this idea
      using a dual-stream rapid serial visual presentation paradigm with centrally
      presented, overlapping streams of letters that changed at different frequencies.
      Participants attended one stream at a time. We predicted that the more focused
      cognitive style associated with higher neuroticism would be reflected in the
      overinvestment of attention in the irrelevant stream of to-be-ignored letters, in
      particular, when the ignored stream was the more salient one. This was expected
      to lead to a smaller difference in power between the attended and unattended
      frequencies. Results showed that power differences between attended and
      unattended streams were negatively correlated with neuroticism scores in direct
      support of our hypothesis. Exploratory correlations also showed that extraversion
      was positively related to the attention difference. As extraversion has been
      contrasted to neuroticism and linked to increased cognitive flexibility and
      control in previous studies, it is possible that this trait may help in
      disengagement from salient stimuli. Together, these results provide the first
      neural correlates of the focused cognitive style idea. That the effect of
      extraversion is seen in the centro-parietal region and the effect of neuroticism
      is seen in the occipital region, indicate that these personality traits may
      affect the hierarchy of visual information processing. These findings provide new
      insight into the influence of personality traits on attention mechanisms and open
      up questions regarding the relationship between neuroticism, extraversion and
      information processing. 

PMID- 24577666
TI  - Stochastic modeling of imperfect Salmonella vaccines in an adult dairy herd.
AB  - Salmonella is a major cause of bacterial foodborne disease. Human salmonellosis
      results in significant public health concerns and a considerable economic burden.
      Dairy cattle are recognized as a key source of several Salmonella serovars that
      are a threat to human health. To lower the risk of Salmonella infection,
      reduction of Salmonella prevalence in dairy cattle is important. Vaccination as a
      control measure has been applied for reduction of preharvest Salmonella
      prevalence on dairy farms. Salmonella vaccines are usually imperfect (i.e.,
      vaccines may provide a partial protection for susceptible animals, reduce the
      infectiousness and shedding level, shorten the infectious period of infected
      animals, and/or curb the number of clinical cases), and evaluation of the
      potential impacts of imperfect Salmonella vaccines at the farm level is valuable
      to design effective intervention strategies. The objective of this study was to
      investigate the impact of imperfect Salmonella vaccines on the stochastic
      transmission dynamics in an adult dairy herd. To this end, we developed a semi
      stochastic and individual-based continuous time Markov chain (CTMC) vaccination
      model with both direct and indirect transmission, and applied the CTMC
      vaccination model to Salmonella Cerro transmission in an adult dairy herd. Our
      results show that vaccines shortening the infectious period are most effective in
      reducing prevalence, and vaccines decreasing host susceptibility are most
      effective in reducing the outbreak size. Vaccines with multiple moderate
      efficacies may have the same effectiveness as vaccines with a single high
      efficacy in reducing prevalence, time to extinction, and outbreak size. Although
      the environment component has negligible contributions to the prevalence, time to
      extinction, and outbreak size for Salmonella Cerro in the herd, the relative
      importance of environment component was not assessed. This study indicates that
      an effective vaccination program against Salmonella Cerro spread in the herd can
      be designed with (1) vaccines with a single high efficacy in reducing either the
      infectious period or susceptibility of the host, or (2) if such single high
      efficacy vaccines are not available, vaccines with multiple moderate efficacies
      may be considered instead. These findings are also of general value for designing
      vaccination program for Salmonella serotypes in livestock. 

PMID- 24577665
TI  - Association between hypogonadism, symptom burden, and survival in male patients
      with advanced cancer.
AB  - BACKGROUND: A high frequency of hypogonadism has been reported in male patients
      with advanced cancer. The current study was performed to evaluate the association
      between low testosterone levels, symptom burden, and survival in male patients
      with cancer. METHODS: Of 131 consecutive male patients with cancer, 119 (91%) had
      an endocrine evaluation of total (TT), free (FT), and bioavailable testosterone
      (BT); high-sensitivity C-reactive protein (CRP); vitamin B12; thyroid-stimulating
      hormone; 25-hydroxy vitamin D; and cortisol levels when presenting with symptoms
      of fatigue and/or anorexia-cachexia. Symptoms were evaluated by the Edmonton
      Symptom Assessment Scale. The authors examined the correlation using the Spearman
      test and survival with the log-rank test and Cox regression analysis. RESULTS:
      The median age of the patients was 64 years; the majority of patients were white
      (85 patients; 71%). The median TT level was 209 ng/dL (normal: >= 200 ng/dL), the
      median FT was 4.4 ng/dL (normal: >= 9 ng/dL), and the median BT was 22.0 ng/dL
      (normal: >= 61 ng/dL). Low TT, FT, and BT values were all associated with worse
      fatigue (P <= .04), poor Eastern Cooperative Oncology Group performance status (P
      <= .05), weight loss (P <= .01), and opioid use (P <= .005). Low TT and FT were
      associated with increased anxiety (P <= .04), a decreased feeling of well-being
      (P <= .04), and increased dyspnea (P <= .05), whereas low BT was only found to be
      associated with anorexia (P = .05). Decreased TT, FT, and BT values were all
      found to be significantly associated with elevated CRP and low albumin and
      hemoglobin. On multivariate analysis, decreased survival was associated with low
      TT (hazards ratio [HR], 1.66; P = .034), declining Eastern Cooperative Oncology
      Group performance status (HR, 1.55; P = .004), high CRP (HR, 3.28; P < .001), and
      decreased albumin (HR, 2.52; P < .001). CONCLUSIONS: In male patients with
      cancer, low testosterone levels were associated with systemic inflammation,
      weight loss, increased symptom burden, and decreased survival. A high frequency
      of hypogonadism has been reported in male patients with advanced cancer. In the
      current study, an increased symptom burden, systemic inflammation, weight loss,
      opioid use, and poor survival were found to be associated with decreased
      testosterone levels in male patients with cancer. Cancer 2014;120:1586-1593. (c)
      2014 American Cancer Society.

PMID- 24577667
TI  - A novel method to enhance the conductance of transitional metal oxide electrodes.
AB  - Transitional metal oxides hold great potential for high capacity anodes. However,
      the low electron conductivity of such materials leads to poor cycling stability
      and inferior rate capability. We reported herein the use of a novel hydrogen
      plasma technology to improve the conductance of metal oxides, which leads great
      success in improving the rate performance of CuO nanotube based anodes. This
      method has the potential to be widely adopted in the field of lithium ion
      batteries and supercapacitors. 

PMID- 24577670
TI  - Isolated spinal Rosai-Dorfman disease misdiagnosed as lymphoplasmacyte-rich
      meningioma by intraoperative histological examination.

PMID- 24577668
TI  - Obesity treatment: results after 4 years of a Nutritional and Psycho-Physical
      Rehabilitation Program in an outpatient setting.
AB  - INTRODUCTION: Obesity is a chronic disease as well as a risk factor for
      cardiovascular, metabolic and osteoarticular diseases, affecting the psychosocial
      health and the quality of life. Recent evidence suggests that the adequate
      treatment of obesity should provide a multidimensional multidisciplinary approach
      including nutritional therapy, psycho-educational classes and physical
      reconditioning/motor rehabilitation. The aim of this approach should be to
      maintain the results over time with a positive impact on the obesity-related
      cardiovascular and metabolic risk. AIM OF THE STUDY: To evaluate the
      effectiveness of a multidisciplinary Nutritional and Psycho-Physical
      Reconditioning Program (NPPRP) in an outpatient setting. MATERIALS AND METHODS:
      The observational prospective cohort study involved subjects, aged from 18 to 65
      years, with a BMI >30 kg/m(2), who were followed up over 48 months. After the
      first nutritional and psychological examination, patients who refused NPPRP were
      treated according to standard nutrition procedures (SNT). Patients were followed
      through monthly medical examinations and then by annual telephonic structured
      interviews for 4 years. Changes in body weight, eating behavior, physical
      activity performance, and the occurrence of clinical obesity-related
      complications were considered as outcome measures. RESULTS: Of 464 enrolled
      patients, 161 (34.7%) took part in the follow-up. From the enrollment to the end
      of follow-up, weight loss was greater in the NPPRP group than in the SNP group (
      8.08 +/- 10 kg versus -3.0 +/- 6 kg). After 4 years eating behavior improved in
      both groups. The percentage of patients who continued to perform physical
      activity was higher in the NPPRP group than in the SNT group (61.0 versus 34.1%).
      The SNT group reported complications more frequently than the NPPRP group:
      hypertension (19 versus 5.8%), dyslipidemia (19.4 versus 12.7%), and skeletal
      problems (26.9 versus 17.5%). The main reasons for drop-out from the
      rehabilitation program were logistic problems (distance or time) in both groups;
      disappointment was higher in the SNT group than in the NPPRP group (37.8 versus
      15.6%). CONCLUSION: A multidimensional multidisciplinary approach including
      nutritional intervention and psycho-physical rehabilitation, set against a
      conventional diet therapy, was more effective in the long-term outcome of obesity
      with regard to weight loss, physical activity, possible eating disorders, and
      obesity-related complications.

PMID- 24577673
TI  - Folding studies of arginine kinase from Euphausia superba using denaturants.
AB  - Arginine kinase (AK) is a key metabolic enzyme for maintaining energy balance in
      invertebrates and studies on AK from Euphausia superba might provide important
      insights into the metabolic enzymes in extreme climatic marine environments. A
      folding study of the AK from E. superba (ESAK) has not yet been reported. To gain
      insights into the structural and folding mechanisms of ESAK, the denaturants
      guanidine HCl and urea were applied in this study. We purified ESAK from the
      muscle of E. superba and evaluated the inhibition kinetics with structural
      unfolding studies under various conditions. The results revealed that ESAK was
      almost completely inactivated when using 1.0 M guanidine HCl and 8.25 M urea. The
      kinetics, characterized via time-interval measurements, showed that the
      inactivations by guanidine HCl and urea were first-order reactions, with the
      kinetic processes shifting from monophases to biphases as concentrations
      increased. Measurements of intrinsic and ANS (anilinonaphthalene-8-sulfonate)
      binding fluorescences showed that guanidine HCl and urea induced conspicuous
      changes in tertiary structures and followed the regular unfolding mechanisms. Our
      study provides information regarding the folding of this muscle-derived metabolic
      enzyme and expands our knowledge and understanding of invertebrate metabolisms.

PMID- 24577674
TI  - Identification of microRNA genes and their mRNA targets in Festuca arundinacea.
AB  - MicroRNAs (miRNAs) have emerged as a novel class of endogenous, small, non-coding
      RNAs of 22 nucleotides (nts) in length, which plays important roles in post
      transcriptional degradation of target mRNA or inhibition of protein synthesis
      through binding the specific sites of target mRNA. Growing evidences have shown
      that miRNAs play an important role in various biological processes, including
      growth and development, signal transduction, apoptosis, proliferation, stress
      responses, maintenance of genome stability, and so on. In our study, we used
      bioinformatic tools to predict miRNA and the corresponding target genes of
      Festuca arundinacea. We used known miRNAs of other plants from miRBase to search
      against expressed sequence tags (EST) databases and genome survey sequences (GSS)
      of F. arundinacea. A total of 8 potential miRNAs were predicted. Phylogenetic
      analysis of the predicted miRNAs revealed that miRNA398c of F. arundinacea
      species was evolutionary highly conserved with Populus trichocarpa. The 8
      potential miRNAs corresponding to 20 target genes were found. Most of the miRNA
      target genes were predicted to encode transcription factors that regulate cell
      growth and development, signaling, metabolism, and other biology processes. By
      bioinformatics methods, we can effectively predict novel miRNAs and its target
      genes and add information to F. arundinacea miRNA database. Moreover, it shows a
      path for the prediction and analysis of miRNAs to those species whose genomes are
      not available through bioinformatics tools.

PMID- 24577675
TI  - The aphasic patient: vulnerability and/or exclusion.
AB  - The aim of this article is to account for the vulnerability of the
      patient/subject affected by aphasia, the loss of acquired language in adults. In
      the case of a sudden onset of aphasia, the patient is often aware of his/her
      disorder from the very onset of the impairment. Vulnerability also affects
      patients suffering from progressive aphasia, mainly due to a collapse of the
      various components of memory. After describing the main types of aphasia in broad
      outline, the study focuses on the isolation and exclusion that they generate,
      starting from a brief study of the emotional impact of the impairment on the
      language-deprived subject. This will be related to the patient's awareness of the
      disorder and the notion of awareness in structuring and using language,
      considered as the expression of thought. Finally, given that aphasia leads to the
      loss of employment, patients enter a phase of social vulnerability. Their speech
      is perceived as strange or even "foreign" by others in ordinary communicative
      contexts. What solutions can be proposed to overcome this state of vulnerability
      and exclusion, which is often felt to be insoluble by the patients themselves? 

PMID- 24577676
TI  - Expeditious synthesis of 1-aminoindane derivatives achieved by [1,4]-hydride
      shift mediated C(sp3)-H bond functionalization.
AB  - Described herein is a [1,4]-hydride shift mediated expeditious synthesis of 1
      aminoindane derivatives. A wide variety of substrates could be employed in this
      reaction to afford various indane derivatives in good to excellent chemical
      yields. Examination of the amine moiety revealed that the sterically hindered
      amine is the key to achieving both low catalyst loading and excellent chemical
      yields. 

PMID- 24577677
TI  - [Mission "Reduction in mortality of the commonest cancer in women"].

PMID- 24577678
TI  - Assessing the usefulness of 18F-fluorodeoxyglucose PET-CT scan after stereotactic
      body radiotherapy for early-stage non-small cell lung cancer.
AB  - BACKGROUND: Although stereotactic body radiation therapy (SBRT) is an established
      treatment option for early-stage lung cancer, there are no guidelines for
      reassessing patients for local treatment failure or intrathoracic recurrence
      after treatment. This study reports the sensitivity, specificity, and positive
      and negative predictive values for 18F-fluorodeoxyglucose (FDG) PET-CT scanning
      when used to evaluate patients after SBRT. METHODS: Charts were reviewed of all
      patients who received SBRT and a subsequent FDG PET-CT scan at a university
      hospital over a 5-year period. Pretreatment and 3-month posttreatment tumor
      characteristics on PET-CT scan and outcome data (adverse events from SBRT, need
      for repeat biopsy, rate of local treatment failure and recurrent disease, and all
      cause mortality) were recorded. RESULTS: Eighty-eight patients were included in
      the study. Fourteen percent of patients (12 of 88) had positive 3-month PET
      scans. Of the positive results, 67% (eight of 12) were true positives. Eighty-six
      percent (76 of 88 patients) had negative 3-month FDG PET-CT scans, with 89% (68
      of 76) true negatives. FDG PET-CT scan performed 3 months after SBRT for non
      small cell lung cancer (NSCLC) had a sensitivity of 50% (95% CI, 0.26-0.75), a
      specificity of 94% (95% CI, 0.89-1.0), a positive predictive value of 67% (95%
      CI, 0.4-0.93), and a negative predictive value of 89% (95% CI, 0.83- 0.96).
      CONCLUSIONS: FDG PET-CT scan 3 months after treatment of NSCLC with SBRT was a
      specific but insensitive test for the detection of recurrence or treatment
      failure. Serial CT scans should be used for early surveillance following SBRT,
      whereas FDG PET-CT scans should be reserved to define suspected metastatic
      disease or to evaluate new abnormalities on CT scan, or for possible reassessment
      later in the follow-up period after radiation-related inflammation subsides.

PMID- 24577679
TI  - Origin of the X1X1X2X2/X1X2Y sex chromosome system of Harttia punctata
      (Siluriformes, Loricariidae) inferred from chromosome painting and FISH with
      ribosomal DNA markers.
AB  - Harttia is a genus in the subfamily Loricariinae that accommodates fishes
      popularly known as armored catfishes. They show extensive karyotypic diversity
      regarding interspecific numerical/structural variation of the karyotypes, with
      the presence of the XX/XY1Y2 multiple sex chromosome system, as found in H.
      carvalhoi. In this context, this study aimed to characterize Harttia punctata
      chromosomally, for the first time, and to infer the rearrangements that
      originated the X1X1X2X2/X1X2Y multiple sex chromosome system present in this
      species. The data obtained in this study, with classical (Giemsa, C-banding and
      AgNORs) and molecular methodologies (fluorescence in situ hybridization) and
      chromosome microdissection, indicated that a translocation between distinct
      acrocentric chromosomes bearing rRNA genes, accompanied by deletions in both
      chromosomes, might have originated the neo-Y chromosome in this species. The data
      also suggest that the multiple sex chromosome systems present in H. carvalhoi and
      H. punctata had an independent origin, evidencing the recurrence of chromosome
      alterations in species from this genus.

PMID- 24577680
TI  - Nephrolithiasis and hypertension: possible links and clinical implications.
AB  - A definite epidemiological association exists between kidney stone disease and
      arterial hypertension, but the pathophysiological mechanisms are still not fully
      understood. Hypercalciuria or inflammation and oxidative stress have been
      proposed as possible links. However, there is more convincing evidence that the
      association between nephrolithiasis and hypertension may be considered as a part
      of the association between kidney stone disease, metabolic syndrome and
      atherosclerosis. From a clinical point of view, this association represents a
      crucial aspect of the clinical management of patients affected by kidney stone
      disease. In order to implement early prevention and treatment of cardiovascular
      and/or renal damage physicians should be encouraged to assess individual
      cardiovascular risk factors in any adult with kidney stones. Consequently,
      patients with kidney stones need a comprehensive approach rather than an
      intervention limited to the urinary tract and focused on stone resolution and
      recurrence prevention. It is time to view kidney stone disease as a systemic
      disorder, associated to or predictive of hypertension, chronic kidney disease,
      bone and cardiovascular damage. All these conditions negatively affect patient
      prognosis. This multi-systemic approach could increase the clinical impact of the
      kidney stone clinic. 

PMID- 24577681
TI  - Clinical approach to the patient with a solid pancreatic mass.
AB  - Diagnosis and clinical work-up of a solid pancreatic mass is a challenging
      problem. Patients' history, laboratory parameters, computed tomography magnetic
      resonance imaging, and endosonography are the cornerstones in diagnosis. Biopsy
      is indicated in selected patients. The main goal of surgical indication is to
      select patients with suspected malignancy who are resectable, but avoid
      unnecessary resections. About 5 % of patients resected due to suspicion of
      malignancy finally present with a benign histology. Autoimmune pancreatitis is
      the most frequent cause of such unnecessary resections. 

PMID- 24577682
TI  - Differences in access points to the ambulatory health care system across Austrian
      federal states.
AB  - BACKGROUND: The nine Austrian regions differ according to demographic parameter,
      health status, and health care structure. It was the aim of this study to analyse
      whether there are also differences in access points towards the level of
      ambulatory care. METHOD: The Austrian Health Interview Survey (2006-2007) data
      with 15,474 participants were used for this cross-sectional analysis. Statistical
      analyses included descriptive statistics as well as multivariate logistic
      regression models and correlations. RESULTS: There were significant differences
      in patients with direct utilisation of specialists without having consulted a
      general practitioner (GP) in the same period in the Austrian regions, with
      highest proportions for women in Vorarlberg (20.3%) and men in Vienna (21.5%) and
      lowest in Burgenland (7.0 and 6.6%, respectively). The specialist/GP ratio
      correlated significantly with the direct specialist utilisation (Spearman
      correlation coefficient: 0.717). CONCLUSION: There are spatial differences in the
      health care utilisation within the Austrian regions, which partly can be
      explained by the disposal of health care structure. These findings are of special
      importance according to the ongoing debate concerning the topic strengthening the
      primary health care sector in Austria.

PMID- 24577684
TI  - Hepatic involvement of Langerhans cell histiocytosis in children--imaging
      findings of computed tomography, magnetic resonance imaging and magnetic
      resonance cholangiopancreatography.
AB  - BACKGROUND: Langerhans cell histiocytosis is a rare disease that occurs mainly in
      children, and hepatic involvement is generally a poor prognostic factor.
      OBJECTIVE: To describe CT and MRI findings of hepatic involvement of Langerhans
      cell histiocytosis in children, especially the abnormal bile duct manifestation
      on magnetic resonance cholangiopancreatography (MRCP). MATERIALS AND METHODS:
      Thirteen children (seven boys, six girls; mean age 28.9 months) were diagnosed
      with disseminated Langerhans cell histiocytosis. They underwent CT (n = 5) or MRI
      (n = 4), or CT and MRI examinations (n = 4) to evaluate the liver involvement.
      RESULTS: Periportal abnormalities presented as band-like or nodular lesions on CT
      and MRI in all 13 children. The hepatic parenchymal lesions were found in the
      peripheral regions of the liver in seven children, including multiple nodules on
      MRI (n = 6), and cystic-like lesions on CT and MRI (n = 3). In 11 of the 13
      children the dilatations of the bile ducts were observed on CT and MRI. Eight of
      the 13 children underwent MR cholangiopancreatography, which demonstrated
      stenoses or segmental stenoses with slight dilatation of the central bile ducts,
      including the common hepatic duct and its first-order branches. The peripheral
      bile ducts in these children showed segmental dilatations and stenoses.
      CONCLUSION: Stenosis of the central bile ducts revealed by MR
      cholangiopancreatography was the most significant finding of liver involvement in
      Langerhans cell histiocytosis in children.

PMID- 24577685
TI  - Improved spatial resolution and lower-dose pediatric CT imaging: a feasibility
      study to evaluate narrowing the X-ray photon energy spectrum.
AB  - This feasibility study has shown that improved spatial resolution and reduced
      radiation dose can be achieved in pediatric CT by narrowing the X-ray photon
      energy spectrum. This is done by placing a hafnium filter between the X-ray
      generator and a pediatric abdominal phantom. A CT system manufactured in 1999
      that was in the process of being remanufactured was used as the platform for this
      study. This system had the advantage of easy access to the X-ray generator for
      modifications to change the X-ray photon energy spectrum; it also had the
      disadvantage of not employing the latest post-imaging noise reduction iterative
      reconstruction technology. Because we observed improvements after changing the X
      ray photon energy spectrum, we recommend a future study combining this change
      with an optimized iterative reconstruction noise reduction technique. 

PMID- 24577687
TI  - Influence of climate-driven shifts in biomass allocation on water transport and
      storage in ponderosa pine.
AB  - Conifers decrease the amount of biomass apportioned to leaves relative to sapwood
      in response to increasing atmospheric evaporative demand. We determined how these
      climate-driven shifts in allocation affect the aboveground water relations of
      ponderosa pine growing in contrasting arid (desert) and humid (montane) climates.
      To support higher transpiration rates, a low leaf:sapwood area ratio (A L/A S) in
      desert versus montane trees could increase leaf-specific hydraulic conductance (K
      L). Alternatively, a high sapwood volume:leaf area ratio in the desert
      environment may increase the contribution of stored water to transpiration.
      Transpiration and hydraulic conductance were determined by measuring sap flow (J
      S) and shoot water potential during the summer (June-July) and fall (August
      September). The daily contribution of stored water to transpiration was
      determined using the lag between the beginning of transpiration from the crown at
      sunrise and J S. In the summer, mean maximum J S was 31.80+/-5.74 and 24.34+/
      3.05 g m(-2) s(-1) for desert and montane trees (a 30.6% difference),
      respectively. In the fall, J S was 25.33+/-8.52 and 16.36+/-4.64 g m(-2) s(-1) in
      desert and montane trees (a 54.8% difference), respectively. J S was
      significantly higher in desert relative to montane trees during summer and fall
      (P<0.05). Predawn and midday shoot water potential and sapwood relative water
      content did not differ between environments. Desert trees had a 129% higher K L
      than montane trees in the summer (2.41*10(-5) versus 1.05*10(-5) kg m(-2) s(-1)
      MPa(-1), P<0.001) and a 162% higher K L in the fall (1.97*10(-5) versus 0.75*10(
      5) kg m(-2) s(-1) MPa(-1), P<0.001). Canopy conductance decreased with D in all
      trees at all measurement periods (P<0.05). Maximum g C was 3.91 times higher in
      desert relative to montane trees averaged over the summer and fall. Water storage
      capacity accounted for 11 kg (11%) and 10.6 kg (17%) of daily transpiration in
      the summer and fall, respectively, and did not differ between desert and montane
      trees. By preventing xylem tensions from reaching levels that cause xylem
      cavitation, high K L in desert ponderosa pine may facilitate its avoidance. Thus,
      the primary benefit of low leaf:sapwood allocation in progressively arid
      environments is to increase K L and not to increase the contribution of stored
      water to transpiration. 

PMID- 24577686
TI  - MR imaging of capitellar ossification: a study in children of different ages.
AB  - BACKGROUND: The capitellar ossification center is used routinely to evaluate
      elbow alignment on radiography. However, whether capitellar ossification is
      central and concentric to support this practice is unknown. OBJECTIVE: To define
      the pattern of capitellar ossification at different ages of childhood. MATERIALS
      AND METHODS: This HIPAA-compliant study was IRB approved. MR imaging examinations
      from 81 children (ages 1-13 years, at least 3 boys and 3 girls in each age group)
      were included. We determined the center points of the ossified capitellum and the
      cartilaginous capitellum on the sagittal and coronal sequences that best showed
      differentiation between cartilage and bone. Percentage offset of the center of
      the ossified capitellum from the center of the cartilaginous capitellum was
      calculated in anterior-posterior, proximal-distal and medial-lateral dimensions,
      and compared across age groups and between genders. Linear regressions were used
      to ascertain the effect of age on percentage offset for all patients and for each
      gender. RESULTS: Capitellar ossification begins eccentrically with sagittal
      anterior proximal offset and coronal medial offset. With age, ossification
      proceeds posteriorly, distally and laterally. Percentage offset gradually
      diminishes with age. The ossified capitellum centralizes in the sagittal plane by
      12-13 years. In the coronal plane, the capitellum ossifies medially beyond the
      proximal radioulnar joint and remains eccentric at 12-13 years. Centralization in
      boys lags in the anterior-posterior dimension. CONCLUSION: Capitellar
      ossification is an eccentric process, with lag in anterior-posterior
      centralization in boys. Medial offset persists at 12-13 years. Recognition of
      this eccentric ossification may allow for more accurate assessment of elbow
      alignment on radiographs, especially in younger children.

PMID- 24577688
TI  - Daily energy expenditure and cell-mediated immunity in pied flycatchers while
      feeding nestlings: interaction with moult.
AB  - Ecological immunology posits a trade-off between parental effort and
      immunocompetence underlying the cost of reproduction. The moult-breeding overlap
      observed in several bird species represents a conflict in resource allocation
      between two energy-demanding processes. Moult processes have been associated with
      enlargements of immune system organs. In the present study. we measured
      simultaneously daily energy expenditure (DEE) and the T-cell-dependent immune
      response of pied flycatchers, Ficedula hypoleuca, caring for grown nestlings. We
      used the doubly labelled water technique and the phytohaemagglutinin (PHA)
      injection assay on both males and females, while recording provisioning rates and
      moult scores. DEE and the PHA response were negatively correlated for females,
      but not for males. A significantly higher proportion of males than females
      initiated moult. Provisioning rates were strongly correlated with DEE for females
      but only for non-moulting males. The DEE of moulting males was marginally
      correlated with moult score. For moulting males, there was a marginally
      significant positive correlation between moult score and immune response. The
      trade-off between DEE and immunity for females could underlie the cost of
      reproduction. However, the moult-breeding overlap found in males may offset this
      trade-off, thereby reducing the implications of immunosuppression for parental
      survival. 

PMID- 24577689
TI  - Phylogenetic analysis of stomach adaptation in digestive strategies in African
      ruminants.
AB  - The stomach morphology of 28 species of artiodactyls that differ in feeding style
      (browser, mixed feeder, grazer) was analysed using a multivariate approach and
      phylogenetic correction in order to test whether stomach morphology was
      correlated with feeding style when body mass was controlled for. A total of 25
      morphological traits of the stomach were used in the analysis. After the effects
      of body mass and phylogeny on stomach morphology were taken into account, there
      was no significant grouping of species according to feeding style. When
      information about the feeding style of each species was included in the analysis,
      the set of morphological traits separated the mixed feeders from the other two
      feeding styles, but grazers and browsers had similar morphological features. Most
      of the variance in stomach morphology was explained by body mass and a lesser
      proportion by phylogeny. The main morphological features that have previously
      been proposed as being adaptations in grazing species, namely, lengthening of the
      retention time of ingesta to achieve an increase in their fibre digestion
      capability by means of a larger relative stomach capacity, a greater subdivision
      of chambers and smaller openings, are not supported by the findings of this
      study. Thus, there is no consistent evidence to support a significant adaptive
      effect of stomach morphology to different diets in the Artiodactyla. 

PMID- 24577690
TI  - Respiratory patterns and metabolism in tenebrionid and carabid beetles from the
      Simpson Desert, Australia.
AB  - The respiratory physiology of four species of Australian desert-dwelling beetle
      was examined using a flow-through respirometry system over the temperature range
      of 20-40 degrees C. The two species of tenebrionid beetles (Heleus waitei and
      Pterohelaeus sp.) did not exhibit the discontinuous gas exchange cycles (DGC), a
      mechanism to possibly reduce respiratory water loss rates, observed in other arid
      dwelling beetles. There were small increases in metabolic rate with temperature
      resulting in a Q 10 of 1.84 for H. waitei and 1.99 for Pterohelaeus sp.
      Furthermore, H. waitei has no increase in metabolic rate over the temperature
      range 25-35 degrees C (Q 10=1). The two species of carabid beetles (Cerotalis sp.
      and Carenum sp.) displayed the DGC respiratory pattern, having long flutter and
      burst periods. Both species also exhibited spiracular movement or muscular
      pumping in the burst period. Relatively low Q 10 values of 1.31 and 1.64 were
      measured for Cerotalis sp. and Carenum sp., respectively. Cerotalis sp. had no
      increase in metabolic rate over the temperature range 20-35 degrees C (Q 10=1).
      In both species the temperature-associated increases in metabolic rate were
      modulated by increases in DGC frequency. All the four beetle species studied have
      fused elytra, a closed subelytral cavity and are nocturnally active, which should
      assist in reducing respiratory water loss rates, and occupy similar
      microhabitats. Thus we propose that the difference in respiratory patterns found
      between the tenebrionid and carabid beetles is related to their thorax
      morphology, food type and food availability. 

PMID- 24577691
TI  - Growth and development of larval green frogs (Rana clamitans) exposed to multiple
      doses of an insecticide.
AB  - Our objective was to determine how green frogs (Rana clamitans) are affected by
      multiple exposures to a sublethal level of the carbamate insecticide, carbaryl,
      in outdoor ponds. Tadpoles were added to 1,000-l ponds at a low or high density
      which were exposed to carbaryl 0, 1, 2, or 3 times. Length of the larval period,
      mass, developmental stage, tadpole survival, and proportion metamorphosed were
      used to determine treatment effects. The frequency of dosing affected the
      proportion of green frogs that reached metamorphosis and the developmental stage
      of tadpoles. Generally, exposure to carbaryl increased rates of metamorphosis and
      development. The effect of the frequency of carbaryl exposure on development
      varied with the density treatment; the majority of metamorphs and the most
      developed tadpoles came from high-density ponds exposed to carbaryl 3 times. This
      interaction suggests that exposure to carbaryl later in the larval period
      stimulated metamorphosis, directly or indirectly, under high-density conditions.
      Our study indicates that exposure to a contaminant can lead to early initiation
      of metamorphosis and that natural biotic factors can mediate the effects of a
      contaminant in the environment. 

PMID- 24577693
TI  - Spatial distributions of male and female strawberry poison frogs and their
      relation to female reproductive resources.
AB  - In many species with a resource-based mating system, males defend resources to
      increase their attractiveness to females. In the strawberry poison frog,
      Dendrobates pumilio, suitable tadpole-rearing sites appear to be a limited
      resource for females. Territorial males have been suggested to defend tadpole
      rearing sites to increase their access to females. In this study we investigate
      the spatial association between tadpole-rearing sites and the sexes as well as
      the spatial association of males and females. If strawberry poison frogs have
      resource defense polygyny, we expect males and females to be associated with
      tadpole-rearing sites and that females will deposit their offspring in tadpole
      rearing sites inside the territories of their mates. To test this hypothesis,
      home range and core area sizes were calculated for both sexes and the association
      patterns were compared in two areas that differed in their abundance of tadpole
      rearing sites. Home ranges and core areas of females were much larger than male
      home ranges. Females showed a clumped distribution in the vicinity of tadpole
      rearing sites. Males were not clumped and were less associated with tadpole
      rearing sites. Females generally did not use tadpole-rearing sites in the
      territory of their mates and we therefore conclude that males did not defend
      tadpole-rearing sites for females. Our data are consistent with the general
      assumption that female distribution is influenced by resource distribution and
      that male distribution depends on female distribution. Nevertheless, the
      distribution of D. pumilio females was also influenced by male spacing patterns.
      Males probably initially establish their core areas where female density is high
      and then females move among territories to sample males. Males compete vigorously
      for places with high female density, the defense of which is likely important for
      enhancing their mating success. In general, the spacing patterns did not differ
      between populations but the sex ratio was strongly female biased in the habitat
      with more tadpole-rearing sites, reflecting the direct reliance of females on
      these resources. 

PMID- 24577692
TI  - The influence of spatial scale and habitat arrangement on diel patterns of
      habitat use by two lowland river fishes.
AB  - There is growing awareness that patterns of habitat use by animals cannot be
      isolated from issues of scale. Recently, techniques have been devised which allow
      empirical testing of hypotheses related to the effects of spatial scale on
      habitat use. We used spatially explicit statistical procedures to examine the
      roles of scale and habitat arrangement in determining fish distribution patterns
      in a reach of an Australian lowland river. Native golden perch and introduced
      common carp were tracked day and night using radiotelemetry over a 10 day period
      and their distributions compared with mapped habitat variables. Golden perch were
      significantly associated with depth, current velocity, substratum and cover at
      larger scales of analysis both day and night, and at smaller scales during the
      day. At night, however, associations between golden perch and habitat variables
      were generally much weaker at small scales. Common carp were generally not
      significantly associated with habitat variables at larger scales of analysis,
      whereas at smaller scales they were associated with depth, current velocity,
      substrate and cover. Associations were generally stronger during the day than at
      night. Our study emphasises the need to consider scale-dependence in studies of
      fish-habitat associations. Management and restoration of fish habitat in lowland
      rivers should be based on an understanding of habitat use at scales relevant for
      the fish rather than at scales arbitrarily defined by humans. 

PMID- 24577694
TI  - Positive and negative interactions between environmental conditions affecting
      Cercocarpus ledifolius seedling survival.
AB  - We evaluated the balance between positive and negative effects of environmental
      conditions on first-year seedling survival of the tree Cercocarpus ledifolius
      during two summers, 1996 and 1997. The experimental design was fully crossed with
      two levels of water, with and without supplementation, two levels of herbivory,
      with and without protection, and three major microhabitats, open interspaces,
      under the canopy of Artemisia tridentata shrubs, and under the canopy of mature
      C. ledifolius trees. Effects of drought and herbivory on seedling survival
      depended on the year. Water supplementation and herbivory protection during the
      dry summer of 1996 (27.7 mm) generally increased seedling survival. Additionally,
      survival tended to be greatest beneath C. ledifolius canopies. More important
      ecologically were the significant interactions. In 1996, water supplementation
      increased survival more with than without herbivory protection. The three-way
      interaction, treatment-microhabitat combination, was most important; by far the
      greatest survival was in the water supplementation and herbivory protection in
      the tree microhabitat. During the wet summer of 1997 (158.5 mm), neither water
      supplementation, herbivory protection, nor microhabitat were significant as main
      effects. The water-supplemented and herbivory-protected treatment again combined
      to yield highest survival, but this time in open interspaces rather than beneath
      trees. Our study shows how the importance of individual limiting factors and the
      relative favorableness of particular microhabitats appear to change across years
      depending on environmental conditions. 

PMID- 24577695
TI  - Leaf pubescence and two-spotted spider mite webbing influence phytoseiid behavior
      and population density.
AB  - Phytoseiid mites, both in agricultural and natural systems, can play an important
      role in the regulation of herbivorous mites. Host plant traits, such as leaf
      pubescence, may influence the dynamics between predator and prey. In this study,
      we examined the influence of leaf surface characteristics (leaf pubescence and
      two-spotted spider mite webbing) on the behavior of two species of predatory
      mites, the generalist Typhlodromus pyri and the spider mite specialist
      Phytoseiulus persimilis. In laboratory trials, T. pyri females consistently spent
      more time and deposited more eggs on leaf discs from trichome-rich apple
      varieties compared to relatively trichome-poor varieties. A similar result was
      found when the choice involved trichome-rich and trichome-poor apple varieties
      planted into the same pot where leaves were allowed to touch so that the mites
      could freely move from leaf to leaf. To further explore the effect of structure
      created by pubescence and to remove possible confounding effects of chemical
      cues, we added cotton fibers to trichome-free bean leaves. T. pyri females
      consistently spent more time and deposited more eggs on the side of a glabrous
      bean leaf with artificial cotton fibers versus the side without added fibers.
      When given a choice between two densities of cotton fibers, T. pyri females
      consistently selected the highest density of available fibers in which to to
      reside and oviposit. T. pyri also preferred cotton fiber configurations in which
      it could move underneath and access the plant surface. The artificial pubescent
      leaf was also used to test the effect of leaf hairs and two-spotted spider mite
      webbing on the behavior of P. persimilis. P. persimilis females preferred
      residing and ovipositing on surfaces with cotton fibers or two-spotted spider
      mite webbing than on bean leaf areas without these structures. When presented a
      choice between cotton fibers or webbing, the behavior of P. persimilis females
      depended on the cotton fiber density. In a mixed-variety apple orchard, we
      investigated the relationship between leaf pubescence and phytoseiid density
      under field conditions. We found a highly significant, positive relationship
      between density of trichomes on leaves and abundance of T. pyri, whereas spider
      mite prey numbers were uniformly low and unrelated to trichome density. These
      field results suggest that the behavioral responses found in our laboratory
      experiments have population consequences. 

PMID- 24577696
TI  - Guanacos and sheep: evidence for continuing competition in arid Patagonia.
AB  - Guanacos (Lama guanicoe) are the only wild ungulate species widely distributed
      across the Patagonian steppe and have undergone a precipitous population decline
      since the introduction of domestic sheep (Ovis aries) 100 years ago. There has
      been speculation that sheep ranching may have played a major role in guanaco
      population decline after monopolising the most productive land because of
      competition for forage plants. Our aim in this work was to estimate guanaco
      abundance and account for its variation across nine different sites, two seasons
      and two years. We conducted over 100 ground surveys of both guanacos and sheep
      and estimated the availability of the preferred plant species both animal species
      might select in their diet. We found that (1) sheep densities were up to 23 times
      higher than guanaco densities in sympatric conditions, (2) at a protected site
      without sheep, guanaco density was one order of magnitude higher than at the rest
      of the sites, (3) across nine different sites, sheep densities alone accounted
      for around 60% of the variation in guanaco abundance, (4) guanaco densities were
      negatively related to both total plant cover and availability of the preferred
      plant species in their diet, which were both positively associated with sheep
      density, and (5) within-site changes in guanaco densities between seasons and
      years were negatively related to changes in sheep densities. Our results are
      consistent with predictions on interspecific competition for food resources,
      although we cannot rule out possible effects of other human-related activities
      influencing guanaco abundance. We conclude that sheep compete with guanacos for
      forage in arid Patagonia. 

PMID- 24577697
TI  - Mutualistic interaction between a weevil and a rust fungus, two parasites of the
      weed Cirsium arvense.
AB  - We present a mutualism between a stem-boring weevil, Apion onopordi Kirby
      (Coleoptera: Apionidae), and a rust fungus, Puccinia punctiformis (Str.) Rohl.
      (Uredinales), both parasites of the creeping thistle, Cirsium arvense (L.) Scop.
      (Asteraceae). Females, but not males, of A. onopordi induced systemic rust
      infections of thistle shoots in the season after they were attacked by the
      weevil, indicating that insect oviposition is a crucial stage in pathogen
      transmission. Adult weevils emerged from systemically infected thistle shoots
      were heavier than weevils from healthy C. arvense shoots. Heavier females had a
      higher fecundity and laid larger eggs. The weevil preferred to deposit eggs in
      systemically rust-infected over healthy thistle shoots, which seemed to be a sub
      optimal host. This is to our knowledge the first report of a mutualistic
      interaction between an herbivorous insect and a biotrophic plant pathogen. The
      mechanism responsible for the advantage of rust-infected shoots for A. onopordi
      causes a different outcome in other thistle herbivores, and therefore can not be
      explained by a general enhancement of nutritional quality in rust-infected
      tissue. This mutualism likely has evolved from a competitive relationship. Unlike
      other thistle herbivores A. onopordi seems to be better suited as mutualist for
      P. punctiformis because of its small impact on the host plant and its feeding
      niche on plant parts not directly associated with pathogen reproduction. 

PMID- 24577698
TI  - Interactions between extrafloral nectaries, aphids and ants: are there
      competition effects between plant and homopteran sugar sources?
AB  - Broad bean (Vicia faba), an annual plant bearing extrafloral nectaries (EFN) at
      the base of the upper leaves, is regularly infested by two aphid species, Aphis
      fabae and Acyrthosiphon pisum. EFN and A. fabae are commonly attended by the ant,
      Lasius niger, while Ac. pisum usually remains uninfested. Sugar concentration and
      sugar composition of extrafloral nectar did not change significantly after aphid
      infestation. The sugar concentration was significantly higher in EFN (c. 271 ug
      ul(-1)) than in the honeydew of A. fabae (37.5 ug ul(-1)). The presence of small
      A. fabae colonies had no significant effect on ant attendance of EFN, which
      remained at the same level as that on plants without A. fabae. Obviously, there
      was no significant competitive effect between the two sugar sources. We suggest
      that the high sugar concentration in the extrafloral nectar may outweigh the
      higher quality (due to the presence of melezitose) and quantity of aphid
      honeydew. Ants and the presence of EFN influenced aphid colony growth. While A.
      fabae colonies generally grew better in the presence of ants, Ac. pisum colonies
      declined on plants with EFN or A. fabae colonies. We conclude that EFN may
      provide some degree of protection for V. faba against those sucking herbivores
      that are not able to attract ants. 

PMID- 24577699
TI  - Vertical zonation of browse quality in tree canopies exposed to a size-structured
      guild of African browsing ungulates.
AB  - We investigated whether the food quality of tree foliage for African savanna
      browsers varies across the feeding height range of the guild. This was to address
      the question of why giraffes (Giraffa camelopardalis) generally feed at a higher
      level in the canopy than is accessible to all other browsers. We defined a
      giraffe browse unit (GBU) as the length of twig corresponding to the average
      "bite" taken by giraffes from two staple browse plants: Acacia nigrescens and
      Boscia albitrunca. We sampled at three study sites in South Africa in the late
      dry season, at each site clipping GBUs at three heights above ground: 0.5 m, 1.5
      m and 2.5 m; these representing the levels typically browsed by small, medium and
      large-bodied browsing ungulates respectively. For each GBU we measured leaf dry
      mass, total N, neutral detergent fibre and condensed tannin, using near-infrared
      spectroscopy calibrated by conventional laboratory analyses. We found no
      differences between height levels with regard to leaf chemistry concentrations,
      but leaf biomass per GBU was significantly higher at the 1.5-m and 2.5-m levels
      than at the 0.5-m level. The larger browsers thus gain a bite-size advantage by
      browsing above the reach of the smaller species. A likely reason for the reduced
      leaf biomass per GBU at the low browsing level is the tendency for small browsers
      to pluck individual leaves from shoots, while large browsers prune off whole
      shoots. We contend that our findings are analogous to those from parallel studies
      on the grazing guild, and are consistent with the hypothesis that the smaller
      members of ungulate guilds competitively displace the larger ones from shared
      feeding sites when resources become restricted. A prediction of this hypothesis
      is that the smaller members of each guild drive the grazing succession from
      behind and maintain browsing height stratification from below. 

PMID- 24577700
TI  - Temporal records of delta(13)C and delta (15)N in North Pacific pinnipeds:
      inferences regarding environmental change and diet.
AB  - Sea lion and seal populations in Alaskan waters underwent various degrees of
      decline during the latter half of the twentieth century and the cause(s) for the
      declines remain uncertain. The stable carbon ((13)C/(12)C) and nitrogen
      ((15)N/(14)N) isotope ratios in bone collagen from wild Steller sea lions
      (Eumetopias jubatus), northern fur seals (Callorhinus ursinus) and harbor seals
      (Phoca vitulina) from the Bering Sea and Gulf of Alaska were measured for the
      period 1951-1997 to test the hypothesis that a change in trophic level may have
      occurred during this interval and contributed to the population declines. A
      significant change in delta(15)N in pinniped tissues over time would imply a
      marked change in trophic level. No significant change in bone collagen delta(15)N
      was found for any of the three species during the past 47 years in either the
      Bering Sea or the Gulf of Alaska. However, the (15)N in the Steller sea lion
      collagen was significantly higher than both northern fur seals and harbor seals.
      A significant decline in delta(13)C (almost 2 0/00 over the 47 years) was evident
      in Steller sea lions, while a declining trend, though not significant, was
      evident in harbor seals and northern fur seals. Changes in foraging location, in
      combination with a trophic shift, may offer one possible explanation.
      Nevertheless, a decrease in delta(13)C over time with no accompanying change in
      delta(15)N suggests an environmental change affecting the base of the foodweb
      rather than a trophic level change due to prey switching. A decline in the
      seasonal primary production in the region, possibly resulting from decreased
      phytoplankton growth rates, would exhibit itself as a decline in delta(13)C.
      Declining production could be an indication of a reduced carrying capacity in the
      North Pacific Ocean. Sufficient quantities of optimal prey species may have
      fallen below threshold sustaining densities for these pinnipeds, particularly for
      yearlings and subadults who have not yet developed adequate foraging skills. 

PMID- 24577701
TI  - Contrasting effects of a cladoceran (Daphnia galeata) and a calanoid copepod
      (Eodiaptomus japonicus) on algal and microbial plankton in a Japanese lake, Lake
      Biwa.
AB  - Macrozooplankton may affect algal and microbial plankton directly through grazing
      or predation and indirectly through nutrient regeneration. They may also affect
      potential prey positively by removing alternative predators. Here, we examined
      the effects of a cladoceran (Daphnia) and a calanoid copepod (Eodiaptomus) on
      algal and microbial plankton in a Japanese lake using in situ experiments in
      which we manipulated the nutrient supply and biomass of these macrozooplankton.
      The response of algal and microbial plankton to macrozooplankton was diverse and
      varied depending on the level of nutrient supply. Eodiaptomus seemed to feed
      mainly on large algae (>20 um) and microzooplankton, while direct grazing by
      Daphnia on algae, bacteria, heterotrophic nanoflagellates (HNF), and
      microzooplankton (ciliates, heliozoa, and rotifers) was pronounced. Trophic
      linkages within these microbial plankton was also suggested; bacteria were grazed
      by HNF and these in turn were grazed by microzooplankton. When the nutrient
      supply was high, both HNF and microzooplankton were exposed to higher amounts of
      algae and lower bacterial abundance. Moreover, nutrient regeneration by daphnids
      and Eodiaptomus copepods seemed to differentially stimulate the growth of algae
      and bacteria. The results suggest that the relationship between macrozooplankton
      and microbial plankton cannot be fully understood without taking into
      consideration not only the feeding characteristics of the macrozooplankton, but
      also the food web structure, the subsidized algal resource, and nutrient
      regeneration from the macrozooplankton. 

PMID- 24577702
TI  - Carbon cycling traits of plant species are linked with mycorrhizal strategy.
AB  - Ecosystem carbon cycling depends strongly on the productivity of plant species
      and the decomposition rates of the litter they produce. We tested the hypothesis
      that classifying plant functional types according to mycorrhizal association
      explains important interspecific variation in plant carbon cycling traits,
      particularly in those traits that feature in a hypothesized feedback between
      vegetation productivity and litter turnover. We compared data from standardized
      'screening' tests on inherent potential seedling relative growth rate (RGR),
      foliar nutrient concentrations, and leaf litter decomposability among 83 British
      plant species of known mycorrhizal type. There was important variation in these
      parameters between mycorrhizal plant types. Plant species with ericoid mycorrhiza
      showed consistently low inherent RGR, low foliar N and P concentrations, and poor
      litter decomposability; plant species with ectomycorrhiza had an intermediate
      RGR, higher foliar N and P, and intermediate to poor litter decomposability;
      plant species with arbuscular-mycorrhiza showed comparatively high RGR, high
      foliar N and P, and fast litter decomposition. Within the woody species subset,
      differentiation in RGR between mycorrhizal types was mostly confounded with
      deciduous versus evergreen habit, but the overall differentiation in litter mass
      loss between mycorrhizal types remained strong within each leaf habit. These
      results indicate that, within a representative subset of a temperate flora,
      ericoid and ectomycorrhizal strategies are linked with low and arbuscular
      mycorrhizal species with high ecosystem carbon turnover. The incorporation of
      mycorrhizal association into current functional type classifications is a
      valuable tool in the assessment of plant-mediated controls on carbon and nutrient
      cycling. 

PMID- 24577703
TI  - No observational evidence for diversity enhancing productivity in Mediterranean
      shrublands.
AB  - In a recent study, Troumbis and Memtas [Oecologia (2000) 125:101-128]
      demonstrated that plant diversity and productivity were correlated in a
      Mediterranean grassland, and presented this as observational evidence that
      diversity may positively influence productivity. However, the hump-backed model
      between biomass or productivity and diversity predicts that productivity and
      diversity should be positively correlated in low-productivity situations because
      both should be limited by the same factors. The sites used by Troumbis and Memtas
      are extremely unproductive (aboveground productivity of all the stands that they
      considered is <20 g/m(2) per year), and well within the productivity range in
      which productivity and diversity should be correlated as according to the hump
      backed model. Evidence is presented that in their study both productivity and
      diversity may have been driven by the same site variables without any causative
      relationship existing between the two. 

PMID- 24577704
TI  - No observational evidence for diversity-enhancing productivity in Mediterranean
      shrublands? : A reply to Wardle.

PMID- 24577705
TI  - Conservation implications of the link between biodiversity and ecosystem
      functioning.
AB  - The relationship between biodiversity and individual ecosystem processes is often
      asymptotic, saturating at relatively low levels, with some species contributing
      more strongly than others. This has cast doubt on arguments for conservation
      based on maintenance of the functioning of ecosystems. However, we argue that the
      link between biodiversity and ecosystem functioning is an important additional
      argument for conservation for several reasons. (1) Although species differ in
      importance to ecosystem processes, we do not believe that this argues for
      preservation of just a few species for two reasons: first, it is nearly
      impossible to identify all species important to the numerous systems and
      processes on which humans depend; second, the important species themselves may
      depend on an unknown number of other species in their communities. (2) Arguments
      for conservation based on ecosystem functioning are complementary to other
      utilitarian, ethical and aesthetic justifications. No single reason will convince
      all people or protect all species, however the combination produces a strong case
      for conservation of biodiversity. (3) Even if the relationship between
      biodiversity and ecosystem functioning is asymptotic at local spatial scales and
      in the short term, effects of biodiversity loss are likely to be important at
      larger temporal and spatial scales. (4) Initial arguments for the importance of
      biodiversity for ecosystem functioning were largely based on a precautionary
      approach (points 1-3). However, we are now moving to a scientific position based
      on accumulating experimental evidence. The future challenge is the integration of
      this scientific research with policy. 

PMID- 24577706
TI  - Ecological variation across a transition in colony-founding behavior in the ant
      Messor pergandei.
AB  - A number of hypotheses have been proposed to explain the evolution of group
      colony foundation (pleometrosis) in ants, but evaluating their importance under
      natural conditions is difficult. The desert seed-harvester ant, Messor pergandei,
      shows regional variation in the incidence of pleometrosis. I investigated whether
      there are ecological differences between the two regions that may explain the
      observed behavioral divergence. Pleometrosis was significantly associated with
      reduced precipitation, lower vegetation biomass, and lower adult colony density.
      These differences are consistent with the hypothesis that additional worker
      production in group colonies increases foraging success rather than competitive
      ability. The data also suggest an additional hypothesis, desiccation resistance,
      that should be explored. Annual variability within regions was high and far
      exceeded the magnitude of the differences seen between regions. Future laboratory
      and field experiments should take such variability into account. 

PMID- 24577707
TI  - Erratum to Limitations on photosynthesis of competing individuals in stands and
      the consequences for canopy structure.

PMID- 24577709
TI  - [Not Available].

PMID- 24577708
TI  - Upconversion fluorescent strip sensor for rapid determination of Vibrio
      anguillarum.
AB  - Here, we report a simple and ultrasensitive upconversion fluorescent strip sensor
      based on NaYF4:Yb,Er nanoparticles (NPs) and the lateral flow
      immunochromatographic assay (LFIA). Carboxyl-modified beta-NaYF4:Yb,Er NPs were
      successfully synthesized by a facile one-pot solvothermal approach, upon further
      coupling with monoclonal antibody, the resultant UCNPs-antibody conjugates probes
      were used in LFIA and served as signal vehicles for the fluorescent reporters. V.
      anguillarum was used as a model analyte to demonstrate the use of this strip
      sensor. The limit of the detection for the fluorescent strip was determined as
      10(2) CFU mL(-1), which is 100 times lower than those displayed by enzyme-linked
      immunosorbent assays, while the time needed for the detection was only 15 min.
      Furthermore, no cross-reaction with other eight pathogens was found, indicating
      the good specificity of the strip. This developed LFIA would offer the potential
      as a useful tool for the quantification of pathogens analysis in the future. 

PMID- 24577711
TI  - Differentiation of heroin and cocaine using dual-energy CT-an experimental study.
AB  - OBJECTIVE: To evaluate if heroin and cocaine can be distinguished using dual
      energy CT. MATERIALS AND METHODS: Twenty samples of heroin and cocaine at
      different concentrations and standardized compression (SC) were scanned in dual
      energy mode on a newest generation Dual Energy 64-row MDCT scanner. CT number,
      spectral graphs, and dual-energy index (DEI) were evaluated. Results were
      prospectively tested on six original samples from a body packer. Wilcoxon's test
      was used for statistical evaluation. RESULTS: Values are given as median and
      range. Under SC, the CT number of cocaine samples (-29.87 Hounsfield unit (HU) [
      125.85; 16.16 HU]) was higher than the CT number of heroin samples (-184.37 HU [
      199.81; -159.25 HU]; p < 0.01). Slope of spectral curves for cocaine was -2.36
      HU/keV [-7.15; -0.67 HU/keV], and for heroin, 1.75 HU/keV [1.28; 2.5 HU/keV] (p <
      0.01). DEI was 0.0352 [0.0081; 0.0528] for cocaine and significantly higher than
      for heroin samples (-0.0127 [-0.0097; -0.0159]; p < 0.001). While CT number was
      inconclusive, all six original packs were correctly classified after evaluation
      of the spectral curve and DEI. In contrast to the CT number, slope of the
      spectral curve and DEI were independent of concentration and compression.
      CONCLUSION: The slope of the spectral curve and the DEI from dual-energy CT data
      can be used to distinguish heroin and cocaine in vitro; these results are
      independent of compression and concentration in the measured range.

PMID- 24577712
TI  - Population genetics of 17 Y-chromosomal STRs loci in Garo and Santal tribal
      populations in Bangladesh.
AB  - Allele frequencies and haplotype diversity of 17 Y-chromosomal short tandem
      repeat (STR) loci included in Y-filerTM PCR amplification kit were studied in 120
      Garo and 139 Santal male individuals residing in two distinct regions of
      Bangladesh. A total of 99 different haplotypes from Garo and 129 different
      haplotypes from Santal individuals were observed with a corresponding
      discrimination capacity (DC) of 0.825 and 0.928, respectively. A comparison of
      the studied data with the published data from Y-STR haplotype reference database
      (YHRD) based on AMOVA revealed that the Garo population is closely related to
      Tripuri population from Tripura, India and Santal population moderately close to
      Munda population from Jharkhand, India. The mainstream Bengali population resides
      at a significant genetic distance from these two studied populations. 

PMID- 24577714
TI  - Middle temporal vein: a fatal hazard in injection cosmetic surgery for temple
      augmentation.

PMID- 24577713
TI  - Assisted suicide by fentanyl intoxication due to excessive transdermal
      application.
AB  - Herein, we report a case of an assisted suicide committed by application of 34
      matrix-based fentanyl-containing transdermal therapeutic systems (TTS) with
      different release rates. The TTS were supplied by the husband but administered by
      the deceased herself. Besides routine systematic toxicological analysis (STA),
      the concentrations of fentanyl and norfentanyl were determined in the blood
      (femoral and heart), urine, stomach content, brain, lung tissue, musculus
      iliopsoas, liver, kidney, bile and in some of the used TTS by LC-MS/MS. Blood
      levels of fentanyl were 60.6 MUg/L in femoral blood and 94.1 MUg/L in heart
      blood. These concentrations are in good concordance with levels described in
      cases with accidental or lethal suicidal fentanyl patch application. The organ
      distribution indicates an influence of post-mortem redistribution. The levels of
      residual fentanyl in the TTS were also determined. STA furthermore revealed
      supratherapeutic levels of bromazepam. Thus, the cause of death was a combination
      of fentanyl and bromazepam intoxication. However, considering the determined
      levels of fentanyl and norfentanyl in the entire set of specimens and the high
      toxicity in comparison to bromazepam, fentanyl was the leading toxic noxa.

PMID- 24577716
TI  - Segmental absence of intestinal musculature.

PMID- 24577715
TI  - Causal inference in longitudinal comparative effectiveness studies with repeated
      measures of a continuous intermediate variable.
AB  - We propose a principal stratification approach to assess causal effects in
      nonrandomized longitudinal comparative effectiveness studies with a binary
      endpoint outcome and repeated measures of a continuous intermediate variable. Our
      method is an extension of the principal stratification approach originally
      proposed for the longitudinal randomized study "Prevention of Suicide in Primary
      Care Elderly: Collaborative Trial" to assess the treatment effect on the
      continuous Hamilton depression score adjusting for the heterogeneity of
      repeatedly measured binary compliance status. Our motivation for this work comes
      from a comparison of the effect of two glucose-lowering medications on a clinical
      cohort of patients with type 2 diabetes. Here, we consider a causal inference
      problem assessing how well the two medications work relative to one another on
      two binary endpoint outcomes: cardiovascular disease-related hospitalization and
      all-cause mortality. Clinically, these glucose-lowering medications can have
      differential effects on the intermediate outcome, glucose level over time.
      Ultimately, we want to compare medication effects on the endpoint outcomes among
      individuals in the same glucose trajectory stratum while accounting for the
      heterogeneity in baseline covariates (i.e., to obtain 'principal effects' on the
      endpoint outcomes). The proposed method involves a three-step model estimation
      procedure. Step 1 identifies principal strata associated with the intermediate
      variable using hybrid growth mixture modeling analyses. Step 2 obtains the
      stratum membership using the pseudoclass technique and derives propensity scores
      for treatment assignment. Step 3 obtains the stratum-specific treatment effect on
      the endpoint outcome weighted by inverse propensity probabilities derived from
      Step 2.

PMID- 24577717
TI  - Structure-guided approach for detecting large domain inserts in protein sequences
      as illustrated using the haloacid dehalogenase superfamily.
AB  - In multi-domain proteins, the domains typically run end-to-end, that is, one
      domain follows the C-terminus of another domain. However, approximately 10% of
      multi-domain proteins are formed by insertion of one domain sequence into that of
      another domain. Detecting such insertions within protein sequences is a
      fundamental challenge in structural biology. The haloacid dehalogenase
      superfamily (HADSF) serves as a challenging model system wherein a variable cap
      domain (~5-200 residues in length) accessorizes the ubiquitous Rossmann-fold core
      domain, with variations in insertion site and topology corresponding to different
      classes of cap types. Herein, we describe a comprehensive computational strategy,
      CapPredictor, for determining large, variable domain insertions in protein
      sequences. Using a novel sequence-alignment algorithm in conjunction with a
      structure-guided sequence profile from 154 core-domain-only structures, more than
      40,000 HADSF member sequences were assigned cap types. The resulting data set
      afforded insight into HADSF evolution. Notably, a similar distribution of cap
      type classes across different phyla was observed, indicating that all cap types
      existed in the last universal common ancestor. In addition, comparative analyses
      of the predicted cap-type and functional assignments showed that different cap
      types carry out similar chemistries. Thus, while cap domains play a role in
      substrate recognition and chemical reactivity, cap-type does not strictly define
      functional class. Through this example, we have shown that CapPredictor is an
      effective new tool for the study of form and function in protein families where
      domain insertion occurs.

PMID- 24577718
TI  - Dissecting adipose tissue lipolysis: molecular regulation and implications for
      metabolic disease.
AB  - Lipolysis is the process by which triglycerides (TGs) are hydrolyzed to free
      fatty acids (FFAs) and glycerol. In adipocytes, this is achieved by sequential
      action of adipose TG lipase (ATGL), hormone-sensitive lipase (HSL), and
      monoglyceride lipase. The activity in the lipolytic pathway is tightly regulated
      by hormonal and nutritional factors. Under conditions of negative energy balance
      such as fasting and exercise, stimulation of lipolysis results in a profound
      increase in FFA release from adipose tissue (AT). This response is crucial in
      order to provide the organism with a sufficient supply of substrate for oxidative
      metabolism. However, failure to efficiently suppress lipolysis when FFA demands
      are low can have serious metabolic consequences and is believed to be a key
      mechanism in the development of type 2 diabetes in obesity. As the discovery of
      ATGL in 2004, substantial progress has been made in the delineation of the
      remarkable complexity of the regulatory network controlling adipocyte lipolysis.
      Notably, regulatory mechanisms have been identified on multiple levels of the
      lipolytic pathway, including gene transcription and translation, post
      translational modifications, intracellular localization, protein-protein
      interactions, and protein stability/degradation. Here, we provide an overview of
      the recent advances in the field of AT lipolysis with particular focus on the
      molecular regulation of the two main lipases, ATGL and HSL, and the intracellular
      and extracellular signals affecting their activity. 

PMID- 24577719
TI  - Molecular evolution of GPCRs: Kisspeptin/kisspeptin receptors.
AB  - Following the discovery of kisspeptin (Kiss) and its receptor (GPR54 or KissR) in
      mammals, phylogenetic studies revealed up to three Kiss and four KissR paralogous
      genes in other vertebrates. The multiplicity of Kiss and KissR types in
      vertebrates probably originated from the two rounds of whole-genome duplication
      (1R and 2R) that occurred in early vertebrates. This review examines compelling
      recent advances on molecular diversity and phylogenetic evolution of vertebrate
      Kiss and KissR. It also addresses, from an evolutionary point of view, the issues
      of the structure-activity relationships and interaction of Kiss with KissR and of
      their signaling pathways. Independent gene losses, during vertebrate evolution,
      have shaped the repertoire of Kiss and KissR in the extant vertebrate species. In
      particular, there is no conserved combination of a given Kiss type with a KissR
      type, across vertebrate evolution. The striking conservation of the biologically
      active ten-amino-acid C-terminal sequence of all vertebrate kisspeptins, probably
      allowed this evolutionary flexibility of Kiss/KissR pairs. KissR mutations,
      responsible for hypogonadotropic hypogonadism in humans, mostly occurred at
      highly conserved amino acid positions among vertebrate KissR. This further
      highlights the key role of these amino acids in KissR function. In contrast, less
      conserved KissR regions, notably in the intracellular C-terminal domain, may
      account for differential intracellular signaling pathways between vertebrate
      KissR. Cross talk between evolutionary and biomedical studies should contribute
      to further understanding of the Kiss/KissR structure-activity relationships and
      biological functions. 

PMID- 24577720
TI  - Postanesthetic death in a cat with myopathy.
AB  - There are few reports of naturally occurring muscular dystrophy in domestic
      animals. Herein, we describe a case of muscular dystrophy in a 4-year-old
      neutered male American domestic shorthair cat that died unexpectedly following
      anesthesia for an elective surgical procedure. Macroscopic muscular hypertrophy
      and histologic evidence of myofiber size variation, mineralization, myofiber
      degeneration, and necrosis were compatible with a diagnosis of muscular
      dystrophy. Extensive endomysial fibrosis was noted histologically in the
      diaphragm. A complete absence of dystrophin protein in Western blot confirmed the
      diagnosis of Duchenne muscular dystrophy. Immunofluorescence microscopy revealed
      reduced levels of dystrophin-associated proteins and an upregulation of utrophin
      at the sarcolemma. Anesthetic deaths can occur in dystrophin-deficient cats, and
      therefore muscular dystrophy and the associated cardiomyopathy should be
      considered in the differential diagnoses for perianesthetic death in cats. 

PMID- 24577723
TI  - Cadmium induces PC12 cells apoptosis via an extracellular signal-regulated kinase
      and c-Jun N-terminal kinase-mediated mitochondrial apoptotic pathway.
AB  - To investigate the role of mitogen-activated protein kinase (MAPK) and downstream
      events in cadmium (Cd)-induced neuronal apoptosis executed via the mitochondrial
      apoptotic pathway, this study used the PC-12 cell line as a neuronal model. The
      result showed that Cd significantly decreased cell viability and the Bcl-2 / Bax
      ratio and increased the percentage of apoptotic cells, release of cytochrome c,
      caspase-3, and poly(ADP-ribose) polymerase cleavage, and nuclear translocation of
      apoptosis-inducing factor (AIF) and endonuclease G. In addition, exposure to Cd
      induced phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N
      terminal kinase (JNK), and p38 MAPK. Inhibition of ERK and JNK, but not p38 MAPK,
      partially protected the cells from Cd-induced apoptosis. ERK and JNK inhibition
      also blocked alteration of the Bcl-2 / Bax ratio and cytochrome c release and
      suppressed caspase-3 and poly(ADP-ribose) polymerase cleavage and AIF and
      endonuclease G nuclear translocation. Taken together, these data suggest that the
      ERK- and JNK-mediated mitochondrial apoptotic pathway played an important role in
      Cd-induced PC12 cells apoptosis.

PMID- 24577724
TI  - Slow relaxation in the first penta-aza Dy(III) macrocyclic complex.
AB  - A new macrocyclic complex DyCl3(LN5).4H2O (1) has been prepared in which the
      Dy(III) ion is equatorially bound by an N5-donor macrocycle (LN5). Ac
      susceptibility data reveal slow relaxation of the magnetisation in zero field
      below 15 K with a distribution of relaxation rates.

PMID- 24577722
TI  - Comparison of sesion severity, distribution, and colonic mucin expression in pigs
      with acute swine dysentery following oral inoculation with "Brachyspira
      hampsonii" or Brachyspira hyodysenteriae.
AB  - Swine dysentery is classically associated with infection by Brachyspira
      hyodysenteriae, the only current officially recognized Brachyspira sp. that
      consistently imparts strong beta-hemolysis on blood agar. Recently, several
      strongly beta-hemolytic Brachyspira have been isolated from swine with clinical
      dysentery that are not identified as B. hyodysenteriae by PCR including the
      recently proposed species "Brachyspira hampsonii." In this study, 6-week-old pigs
      were inoculated with either a clinical isolate of "B. hampsonii" (EB107; n = 10)
      clade II or a classic strain of B. hyodysenteriae (B204; n = 10) to compare gross
      and microscopic lesions and alterations in colonic mucin expression in pigs with
      clinical disease versus controls (n = 6). Gross lesions were similar between
      infected groups. No histologic difference was observed between infected groups
      with regard to neutrophilic inflammation, colonic crypt depth, mucosal
      ulceration, or hemorrhage. Histochemical and immunohistochemical evaluation of
      the apex of the spiral colon revealed decreased expression of sulphated mucins,
      decreased expression of MUC4, and increased expression of MUC5AC in diseased pigs
      compared to controls. No difference was observed between diseased pigs in
      inoculated groups. This study reveals significant alterations in colonic mucin
      expression in pigs with acute swine dysentery and further reveals that these and
      other microscopic changes are similar following infection with "B. hampsonii"
      clade II or B. hyodysenteriae. 

PMID- 24577721
TI  - Lesion profiling and subcellular prion localization of cervid chronic wasting
      disease in domestic cats.
AB  - Chronic wasting disease (CWD) is an efficiently transmitted, fatal, and
      progressive prion disease of cervids with an as yet to be fully clarified host
      range. While outbred domestic cats (Felis catus) have recently been shown to be
      susceptible to experimental CWD infection, the neuropathologic features of the
      infection are lacking. Such information is vital to provide diagnostic power in
      the event of natural interspecies transmission and insights into host and strain
      interactions in interspecies prion infection. Using light microscopy and
      immunohistochemistry, we detail the topographic pattern of neural spongiosis (the
      "lesion profile") and the distribution of misfolded prion protein in the primary
      and secondary passage of feline CWD (Fel(CWD)). We also evaluated cellular and
      subcellular associations between misfolded prion protein (PrP(D)) and central
      nervous system neurons and glial cell populations. From these studies, we (1)
      describe the novel neuropathologic profile of Fel(CWD), which is distinct from
      either cervid CWD or feline spongiform encephalopathy (FSE), and (2) provide
      evidence of serial passage-associated interspecies prion adaptation. In addition,
      we demonstrate through confocal analysis the successful co-localization of PrP(D)
      with neurons, astrocytes, microglia, lysosomes, and synaptophysin, which, in
      part, implicates each of these in the neuropathology of Fel(CWD). In conclusion,
      this work illustrates the simultaneous role of both host and strain in the
      development of a unique Fel(CWD) neuropathologic profile and that such a profile
      can be used to discriminate between Fel(CWD) and FSE. 

PMID- 24577725
TI  - Sex differences in the risk of stroke and HbA(1c) among diabetic patients.
AB  - AIMS/HYPOTHESIS: Sex differences in macrovascular disease, especially in stroke,
      are observed across studies of epidemiology. We studied a large sample of
      patients with type 2 diabetes to better understand the relationship between
      glycaemic control and stroke risk. METHODS: We prospectively investigated the sex
      specific association between different levels of HbA(1c) and incident stroke risk
      among 10,876 male and 19,278 female patients with type 2 diabetes. RESULTS:
      During a mean follow-up of 6.7 years, 2,949 incident cases of stroke were
      identified. The multivariable-adjusted HRs of stroke associated with different
      levels of HbA(1c) at baseline (HbA(1c) <6.0% [<42 mmol/mol], 6.0-6.9% [42-52
      mmol/mol] [reference group], 7.0-7.9% [53-63 mmol/mol], 8.0-8.9% [64-74
      mmol/mol], 9.0-9.9% [75-85 mmol/mol] and >=10.0% [>=86 mmol/mol]) were 0.96 (95%
      CI 0.80, 1.14), 1.00, 1.04 (0.85, 1.28), 1.11 (0.89, 1.39), 1.10 (0.86, 1.41) and
      1.22 (0.92, 1.35) (p for trend = 0.66) for men, and 1.03 (0.90, 1.18), 1.00, 1.09
      (0.94, 1.26), 1.19 (1.00, 1.42), 1.32 (1.09, 1.59) and 1.42 (1.23, 1.65) (p for
      trend <0.001) for women, respectively. The graded association between HbA(1c)
      during follow-up and stroke risk was observed among women (p for trend = 0.066).
      When stratified by race, whether with or without glucose-lowering agents, this
      graded association of HbA(1c) with stroke was still present among women. When
      stratified by age, the adjusted HRs were significantly higher in women older than
      55 years compared with younger women. CONCLUSIONS/INTERPRETATION: The current
      study suggests a graded association between HbA1c and the risk of stroke among
      women with type 2 diabetes. Poor control of blood sugar has a stronger effect in
      diabetic women older than 55 years.

PMID- 24577726
TI  - Protective effect of carvacrol on acute lung injury induced by lipopolysaccharide
      in mice.
AB  - Carvacrol, the major component of Plectranthus amboinicus, has been known to
      exhibit anti-inflammatory activities. The aim of this study was to investigate
      the effects of carvacrol on lipopolysaccharide (LPS)-induced endotoxemia and
      acute lung injury (ALI) in mice. Mice were injected intraperitoneally (i.p.) with
      LPS and the mortality of mice for 7 days were observed twice a day. Meanwhile,
      the protective effect of carvacrol (20, 40 or 80 mg/kg) on LPS-induced
      endotoxemia were detected. Using an experimental model of LPS-induced ALI, we
      examined the effect of carvacrol in resolving lung injury. The results showed
      that carvacrol could improve survival during lethal endotoxemia and attenuate LPS
      induced ALI in mice. The anti-inflammatory mechanisms of carvacrol may be due to
      its ability to inhibit NF-kappaB and MAPKs signaling pathways, thereby inhibiting
      inflammatory cytokines TNF-alpha, IL-6 and IL-1beta production. 

PMID- 24577727
TI  - Modular analysis of bioinformatics demonstrates a critical role for NF-kappaB in
      macrophage activation.
AB  - To achieve the goal of identifying the gene groups that regulated macrophage
      activation, a total of 925 differentially expressed genes of activated
      macrophages were found at the intersection of the three series (GSE5099-1,
      GSE5099-2, and GSE18686) from the Gene Expression Omnibus (GEO) database, and a
      sub-network was constructed based on the protein-protein interaction (PPI)
      network. Four communities (K = 3) were identified from the sub-network using the
      CFinder software. Community 1 was considered as the gene group of interest base
      on the heat map. GO-BP and KEGG enrichment analysis with the DAVID software
      showed that the functions of the 14 genes in community 1 were mainly related to
      the NF-kappaB pathway. A network was constructed using the Cytoscape software.
      The diagram showed that STAT1, NFKBIA, NFKAIB, JUN, and RELA were the key genes
      in the regulation of macrophage activation. Among these genes, RELA (NF-kappaB
      P65) was an important member of the NF-kappaB family, while NFKBIA (IkappaBalpha)
      and NFKAIB (IkappaBbeta) were the inhibitory factors of NF-kappaB. Small
      molecules capable of regulating these five genes were identified via the CMap
      software, and a network diagram was generated using the Cytoscape software to
      provide a reference for the development of new drugs that regulate macrophage
      activation.

PMID- 24577730
TI  - Retraction Note to: Isolated central retinal artery occlusion as an initial
      presentation of paroxysmal nocturnal hemoglobinuria and successful long-term
      prevention of systemic thrombosis with eculizumab (Jpn J Ophthalmol. 2013;57:424
      8).

PMID- 24577729
TI  - An immuno-epidemiological model with threshold delay: a study of the effects of
      multiple exposures to a pathogen.
AB  - An immuno-epidemiological model of pathogen transmission is developed. This model
      incorporates two main features: (i) the epidemiological model includes within
      host pathogen dynamics for an infectious disease, (ii) the susceptible
      individuals to the infection experience a series of exposures via the pathogen
      before becoming infectious. It is shown that this model leads naturally to a
      system of differential delay equations of the threshold type and that these
      equations can be transformed, in a biologically natural way, to differential
      equations with state-dependent delay. An interesting dynamical behavior of the
      model is the bistability phenomena, when the basic reproductive ratio R0 is less
      than unity, which raises many new challenges to effective infection control.

PMID- 24577728
TI  - AS252424, a PI3Kgamma inhibitor, downregulates inflammatory responsiveness in
      mouse bone marrow-derived mast cells.
AB  - PI3Kgamma is known to play an important role in inflammation and immune
      responses. Mast cells are closely involved in the initiation and regulation of
      immune responses and allergic inflammatory reactions. AS252424 is a specific
      PI3Kgamma inhibitor. Until now, the anti-inflammatory effect of AS252424 on mast
      cells has not been reported. In this study, we investigated the anti-inflammatory
      effects of AS252424 on the inflammatory mediators in activated bone marrow
      derived mast cells (BMMCs). AS252424 dramatically attenuated c-Kit ligand (KL)
      induced leukotriene C4 (LTC4) generation and degranulation in BMMCs.
      Downregulating phosphorylation of cytosolic phospholipase A2 (cPLA2) and mitogen
      activated protein kinase (MAPK) and inhibition of Ca(2+) liberation in BMMCs
      might be involved in the anti-inflammatory effects. These results suggested that
      AS252424 might be considered as a chemical tool or a drug candidate for
      prevention and therapy of inflammatory disease. 

PMID- 24577731
TI  - Tailoring crystallization: towards high-performance poly(lactic acid).
AB  - Poly(lactic acid) (PLA) is one of the most promising alternatives for
      petrochemical-based plastics. Crystallization mediation provides the simplest and
      most practical approach for enhancing the properties of PLA. Here, recent
      advances in understanding the relationship between crystalline structure and
      properties of PLA are summarized. Methods for manipulating crystallization
      towards high-performance PLA materials are introduced. 

PMID- 24577734
TI  - Mechanisms linking in utero stress to altered offspring behaviour.
AB  - Development in utero is recognised as a determinant of health in later life, a
      concept known as early life 'programming'. Several studies in humans have now
      shown a link between in utero stressors of maternal stress, anxiety and
      depression and adverse behavioural outcomes for the offspring including poorer
      cognitive function and behavioural and emotional problems. These behaviours are
      observed from the very early neonatal period and appear to persist through to
      adulthood. Underlying mechanisms are not known but overexposure of the developing
      foetus to glucocorticoids has been proposed. Dysregulation of the maternal and
      offspring hypothalamic-pituitary-adrenal (HPA) axis has been proposed as a
      mechanism linking in utero stress with offspring behavioural outcomes. Studies
      suggest that altered circulating levels of maternal cortisol during pregnancy
      and/or changes in placental gene expression or methylation, which result in
      increased glucocorticoid transfer to the developing foetus, are linked to changes
      in offspring behaviour and in activity of the offspring HPA axis. Further
      understanding of the underlying pathways and identification of any gestation of
      vulnerability are needed to help design interventions to reduce in utero stress
      and improve behavioural outcomes in the offspring. 

PMID- 24577732
TI  - A green, multicomponent, regio- and stereo-selective 1,3-dipolar cycloaddition of
      azides and azomethine ylides generated in situ with bifunctional dipolarophiles
      using PEG-400.
AB  - A series of novel dispiropyrrolidine-linked 1,2,3-triazole derivatives have been
      prepared by one-pot, four-component protocol that employed 5-arylidene-3-(prop-2
      ynyl)thiazolidine-2,4-dione, isatin, sarcosine and substituted azides using Cu(I)
      generated in situ as catalyst in PEG-400 as a highly efficient and green media.
      This is the first report of a four-component reaction involving a classical
      Huisgen reaction, in which the two dipolar moieties (substituted azides and in
      situ generated azomethine ylides) react with acetylenic and olefinic
      dipolarophiles, respectively. The 1,3-dipolar cycloaddition proceeds in a highly
      regio- and stereo-selective manner. This methodology can be an ideal tool for the
      preparation of biologically important five-membered heterocyclic compounds in one
      pot. 

PMID- 24577733
TI  - A future of the model organism model.
AB  - Changes in technology are fundamentally reframing our concept of what constitutes
      a model organism. Nevertheless, research advances in the more traditional model
      organisms have enabled fresh and exciting opportunities for young scientists to
      establish new careers and offer the hope of comprehensive understanding of
      fundamental processes in life. New advances in translational research can be
      expected to heighten the importance of basic research in model organisms and
      expand opportunities. However, researchers must take special care and implement
      new resources to enable the newest members of the community to engage fully with
      the remarkable legacy of information in these fields. 

PMID- 24577735
TI  - Responsibility-sensitive fairness in health financing: judgments in four European
      countries.
AB  - Risky health behaviours substantially increase medical and social costs. We
      document the extent to which a sample of European students (from Denmark, France,
      Italy and Sweden) consider that individuals should assume the financial burden of
      paying the costs of risky behaviour. We test the acceptability of different ways
      of financing costs because of ill health that is more or less associated with
      risky behaviour in accordance with a normative framework relating to
      responsibility-sensitive fairness. We find that the majority of students agree
      with assuming financial responsibility for risky behaviours and that there should
      be compensation for unfavourable circumstances. Students agree that two
      individuals with the same responsibility variables should make an equal financial
      contribution and that more effort in maintaining health for given circumstances
      should be rewarded with a lower financial contribution. The specific health
      context and the type of risky behaviours involved matter in determining
      perceptions of justice in health financing.

PMID- 24577737
TI  - Risk factors and antecedent life events in the development of anorexia nervosa: a
      Portuguese case-control study.
AB  - OBJECTIVE: The aetiology of anorexia nervosa (AN) is considered to be
      multifactorial. This study aims to identify potential risk factors for AN and
      whether these factors are specific to AN or precede the development of
      psychiatric disorders in general and to identify specific life events in the 12
      months immediately preceding the onset of eating disorder (ED) symptoms. METHOD:
      A case-control design was used to compare a group of women who meet Diagnostic
      and Statistical Manual of Mental Disorders, Fourth Edition criteria for AN (N =
      86) with healthy controls (N = 86) and with a group of controls with other
      psychiatric disorders (N = 68), each group matched to the AN patients by age and
      parental socioeconomic status bands. Risk factors were assessed by interviewing
      each person with the Oxford Risk Factor Interview. RESULTS: Women with AN
      reported significantly higher rates of perfectionism, negative attitudes toward
      parents' shape and weight, significant concern about feeling fat and a family
      history of AN or bulimia nervosa. Critical comments about weight, shape or eating
      was the most notable event in the year preceding AN onset. DISCUSSION:
      Perfectionism and a family history of ED emerged as the most convergent findings
      in the development of AN, along with being critical toward parents' shape and
      weight, and feeling fat. Critical comments about appearance and eating seem to be
      an important precipitating factor in AN onset.

PMID- 24577738
TI  - Screening of Ganoderma strains with high polysaccharides and ganoderic acid
      contents and optimization of the fermentation medium by statistical methods.
AB  - Polysaccharides and ganoderic acids (GAs) are the major bioactive constituents of
      Ganoderma species. However, the commercialization of their production was limited
      by low yield in the submerged culture of Ganoderma despite improvement made in
      recent years. In this work, twelve Ganoderma strains were screened to efficiently
      produce polysaccharides and GAs, and Ganoderma lucidum 5.26 (GL 5.26) that had
      been never reported in fermentation process was found to be most efficient among
      the tested stains. Then, the fermentation medium was optimized for GL 5.26 by
      statistical method. Firstly, glucose and yeast extract were found to be the
      optimum carbon source and nitrogen source according to the single-factor tests.
      Ferric sulfate was found to have significant effect on GL 5.26 biomass production
      according to the results of Plackett-Burman design. The concentrations of
      glucose, yeast extract and ferric sulfate were further optimized by response
      surface methodology. The optimum medium composition was 55 g/L of glucose, 14 g/L
      of yeast extract, 0.3 g/L of ferric acid, with other medium components unchanged.
      The optimized medium was testified in the 10-L bioreactor, and the production of
      biomass, IPS, total GAs and GA-T enhanced by 85, 27, 49 and 93 %, respectively,
      compared to the initial medium. The fermentation process was scaled up to 300-L
      bioreactor; it showed good IPS (3.6 g/L) and GAs (670 mg/L) production. The
      biomass was 23.9 g/L in 300-L bioreactor, which was the highest biomass
      production in pilot scale. According to this study, the strain GL 5.26 showed
      good fermentation property by optimizing the medium. It might be a candidate
      industrial strain by further process optimization and scale-up study. 

PMID- 24577739
TI  - Internal hernia caused by epiploic appendices successfully treated by single
      incision laparoscopic surgery (SILS).
AB  - Internal hernia is a rare and often overlooked cause of small bowel obstruction.
      We report a case of internal hernia with an orifice composed of epiploic fat,
      successfully diagnosed and treated by single-incision laparoscopic surgery. This
      is the second report of this type of internal hernia and the first reported case
      addressed laparoscopically. Although the use of laparoscopy for the treatment of
      small bowel obstruction is not firmly established today, it may be beneficial for
      both its diagnostic value and as a less invasive treatment. 

PMID- 24577736
TI  - Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for
      peritoneal carcinomatosis: outcomes from a single tertiary institution.
AB  - BACKGROUND: Cytoreductive surgery (CRS) with heated intraperitoneal chemotherapy
      (HIPEC) is an effective but morbid procedure in the treatment of peritoneal
      carcinomatosis. We report our outcomes at a single tertiary institution. METHOD:
      A total of 170 consecutive patients underwent CRS-HIPEC for peritoneal
      carcinomatosis between July 2007 and August 2012. The peritoneal cancer index (1
      39) was used for peritoneal carcinomatosis (PC) staging. Mitomycin C (88.8%) was
      administered intraperitoneally at 42  degrees C for 90 mins. Risk factors
      associated with major morbidities were analyzed. The Kaplan-Meier method was used
      for survival analyses. RESULTS: The mean age was 55.1 (+/-11.3) years, and the
      majority (77.1%) of patients had complete cytoreduction (CC0-1). Tumor types
      included colorectal (n = 51, 30.0%), appendiceal (n = 50, 29.4 %), pseudomyxoma
      peritonei (n = 16, 9.4%), and other (n = 53, 31.2%). Factors associated with
      major complications were estimated blood loss (>400 ml), length of stay (>1
      week), intraoperative blood transfusion, operative time (>6 h), and bowel
      anastomosis. Intraoperative blood transfusion was the only independent prognostic
      factor on multivariate analysis (p = 0.031). Median follow-up was 15.7 months (+/
      1.2). The recurrence rates for colorectal and appendiceal carcinoma at 1 and 3
      years were 40%, 53.5% and 68%, 79.1%, respectively. The 1- and 3-year overall
      survival for colorectal and appendiceal carcinomatosis was 74.0%, 32.5% and
      89.4%, 29.3%, respectively. Intraoperative peritoneal cancer index (PCI) score
      (>16) and need for blood transfusion were factors independently associated with
      poor survival (p < 0.05). CONCLUSION: Our single institution experience of
      CRS/HIPEC procedures for peritoneal carcinomatosis demonstrates acceptable
      perioperative outcome and long-term survival. Optimal cytoreduction was achieved
      in the majority of cases. Intraoperative PCI > 16 was associated with poor
      survival. This series supports the safety of CRS-HIPEC in selected patients.

PMID- 24577741
TI  - Integration and proliferation of Pseudomonas aeruginosa PA01 in multispecies
      biofilms.
AB  - Despite an increased awareness of biofilm formation by pathogens and the role of
      biofilms in human infections, the potential role of environmental biofilms as an
      intermediate stage in the host-to-host cycle is poorly described. To initiate
      infection, pathogens in biofilms on inanimate environmental surfaces must detach
      from the biofilm and be transmitted to a susceptible individual in numbers large
      enough to constitute an infectious dose. Additionally, while detachment has been
      recognized as a discrete event in the biofilm lifestyle, it has not been studied
      to the same extent as biofilm development or biofilm physiology. Successful
      integration of Pseudomonas aeruginosa strain PA01 expressing green fluorescent
      protein (PA01GFP), employed here as a surrogate pathogen, into multispecies
      biofilm communities isolated and enriched from sink drains in public washrooms
      and a hospital intensive care unit is described. Confocal laser scanning
      microscopy indicated that PA01GFP cells were most frequently located in the
      deeper layers of the biofilm, near the attachment surface, when introduced into
      continuous flow cells before or at the same time as the multispecies drain
      communities. A more random integration pattern was observed when PA01GFP was
      introduced into established multispecies biofilms. Significant numbers of single
      PA01GFP cells were continuously released from the biofilms to the bulk liquid
      environment, regardless of the order of introduction into the flow cell.
      Challenging the multispecies biofilms containing PA01GFP with sub-lethal
      concentrations of an antibiotic, chelating agent and shear forces that typically
      prevail at distances away from the point of treatment showed that environmental
      biofilms provide a suitable habitat where pathogens are maintained and protected,
      and from where they are continuously released. 

PMID- 24577740
TI  - Comparisons of the fungal and protistan communities among different marine sponge
      holobionts by pyrosequencing.
AB  - To date, the knowledge of eukaryotic communities associated with sponges remains
      limited compared with prokaryotic communities. In a manner similar to
      prokaryotes, it could be hypothesized that sponge holobionts have
      phylogenetically diverse eukaryotic symbionts, and the eukaryotic community
      structures in different sponge holobionts were probably different. In order to
      test this hypothesis, the communities of eukaryota associated with 11 species of
      South China Sea sponges were compared with the V4 region of 18S ribosomal
      ribonucleic acid gene using 454 pyrosequencing. Consequently, 135 and 721 unique
      operational taxonomic units (OTUs) of fungi and protists were obtained at 97 %
      sequence similarity, respectively. These sequences were assigned to 2 phyla of
      fungi (Ascomycota and Basidiomycota) and 9 phyla of protists including 5 algal
      phyla (Chlorophyta, Haptophyta, Streptophyta, Rhodophyta, and Stramenopiles) and
      4 protozoal phyla (Alveolata, Cercozoa, Haplosporidia, and Radiolaria) including
      47 orders (12 fungi, 35 protists). Entorrhizales of fungi and 18 orders of
      protists were detected in marine sponges for the first time. Particularly,
      Tilletiales of fungi and Chlorocystidales of protists were detected for the first
      time in marine habitats. Though Ascomycota, Alveolata, and Radiolaria were
      detected in all the 11 sponge species, sponge holobionts have different fungi and
      protistan communities according to OTU comparison and principal component
      analysis at the order level. This study provided the first insights into the
      fungal and protistan communities associated with different marine sponge
      holobionts using pyrosequencing, thus further extending the knowledge on sponge
      associated eukaryotic diversity.

PMID- 24577743
TI  - [Sexual complaints and dysfunction among PLHIV receiving ARV treatment for ten
      years in Senegal].
AB  - The sexual health of people who have been living with HIV (PLHIV) and who have
      been receiving ARV drug treatment for several years is still a virtually
      unexplored topic in Africa today. A study was conducted in Senegal on people who
      have been treated with ARVs for ten years. Half of those interviewed believe that
      their sexuality has deteriorated. HIV infection has become a chronic disease in
      which sexual dysfunction related to the disease or age is interpreted in the
      context of popular representations of HIV infection and those on sexuality
      defined by social norms. 

PMID- 24577742
TI  - Correlation between optical coherence tomographic hyperreflective foci and visual
      outcomes after intravitreal bevacizumab for macular edema in branch retinal vein
      occlusion.
AB  - PURPOSE: To investigate the correlation between hyperreflective foci (HF) on
      spectral-domain optical coherence tomography at baseline and visual outcomes
      after intravitreal bevacizumab injection (IVB) in branch retinal vein occlusion.
      METHODS: We retrospectively studied 97 eyes of 97 patients with macular edema
      secondary to BRVO, who were treated with IVB. The eyes were divided into three
      groups according to the location of HF on SD-OCT: HF in outer retinal layers, HF
      in inner retinal layers, and no HF. The baseline and final best-corrected visual
      acuity (BCVA), foveal thickness (FT), external limiting membrane (ELM) status,
      junction between photoreceptor inner and outer segments (IS/OS) status, and the
      number of HF were evaluated and compared among three groups. RESULTS: Baseline
      BCVA was correlated with baseline FT (R = 0.366, p < 0.001), but final BCVA was
      not correlated with final FT (R = -0.008, p = 0.942). Baseline BCVA was
      significantly better in eyes with intact ELM at baseline (p = 0.006), and final
      BCVA was significantly better in eyes with intact ELM and IS/OS at final visit (p
      <  0.001, p = 0.003 respectively). At the final visit, 15 of 37 eyes (40.5%) with
      HF in outer retinal layers had a disrupted ELM (p = 0.001), while 28 of 37 eyes
      (75.7%) with HF in outer retinal layers had a disrupted IS/OS (p <  0.001). Final
      BCVA was poorer in eyes with HF in outer retinal layers groups than those in the
      other two groups (p <  0.001), although baseline BCVA was not different between
      them. CONCLUSIONS: HF on SD-OCT at baseline might predict the photoreceptor
      status and final VA after IVB in BRVO.

PMID- 24577744
TI  - VPS53 mutations cause progressive cerebello-cerebral atrophy type 2 (PCCA2).
AB  - BACKGROUND: Progressive cerebello-cerebral atrophy (PCCA) leading to profound
      mental retardation, progressive microcephaly, spasticity and early onset
      epilepsy, was diagnosed in four non-consanguineous apparently unrelated families
      of Jewish Moroccan ancestry. Common founder mutation(s) were assumed. METHODS:
      Genome-wide linkage analysis and whole exome sequencing were done, followed by
      realtime PCR and immunofluorescent microscopy. RESULTS: Genome-wide linkage
      analysis mapped the disease-associated gene to 0.5 Mb on chromosome 17p13.3.
      Whole exome sequencing identified only two mutations within this locus, which
      were common to the affected individuals: compound heterozygous mutations in
      VPS53, segregating as expected for autosomal recessive heredity within all four
      families, and common in Moroccan Jews (~1:37 carrier rate). The Golgi-associated
      retrograde protein (GARP) complex is involved in the retrograde pathway recycling
      endocytic vesicles to Golgi; c.2084A>G and c.1556+5G>A VPS53 founder mutations
      are predicted to affect the C-terminal domain of VPS53, known to be critical to
      its role as part of this complex. Immunofluorescent microscopy demonstrated
      swollen and abnormally numerous CD63 positive vesicular bodies, likely
      intermediate recycling/late endosomes, in fibroblasts of affected individuals.
      CONCLUSIONS: Autosomal recessive PCCA type 2 is caused by VPS53 mutations.

PMID- 24577745
TI  - Metal-organic frameworks as stationary phases for mixed-mode separation
      applications.
AB  - Polymorphic metal-organic framework (MOF) materials offer a platform for small
      scale separation of complex mixtures of polycyclic aromatic hydrocarbons (PAHs)
      and polar compounds. Retention factors show dependence on both analyte dimensions
      and polarity, suggesting mixed-mode separation, allowing complete resolution of
      some analytes from multi-component mixtures. 

PMID- 24577746
TI  - Bidirectional associations between parenting behavior and child callous
      unemotional traits: does parental depression moderate this link?
AB  - The current study longitudinally examined bidirectional associations between
      callous-unemotional (CU) traits and parenting dimensions. This study extended the
      literature by examining whether parental depression moderated these relations in
      a pre-adolescent sample. Proposed relations were examined using a longitudinal
      sample of 120 aggressive children (59.6 % male) who were in the 4th grade (M =
      10.56 years, SD = 0.56) at baseline and were followed annually over 4 years. A
      series of generalized estimating equation (GEE) models were used to examine
      proposed relations. At the first order level, corporal punishment (p < . 001) and
      poor supervision/monitoring predicted increases in CU traits (p = 0.03) however,
      the inverse relations were not found. Importantly, parental depression moderated
      the link between corporal punishment and CU traits. Specifically, at high levels
      of depression, corporal punishment was predictive of increases in CU traits, but
      was unrelated to CU traits at low levels of depression. These findings aid in our
      understanding of the link between corporal punishment and CU traits by
      highlighting conditions under which certain parenting behaviors have an impact on
      CU traits, which in turn, may have important intervention implications. Further
      clinical implications, limitations and future directions are discussed. 

PMID- 24577747
TI  - Effects of cognitive behavioral therapy on insomnia of maintenance hemodialysis
      patients.
AB  - The objective of the study was to evaluate the effects of cognitive behavioral
      therapy [sleep-related behavior modification and progressive muscle relaxation on
      insomnia of maintenance hemodialysis (MHD) patients] on improving insomnia of MHD
      patients. 103 MHD patients complicated with insomnia were randomly assigned to
      treatment (n = 52) and control (n = 51) groups. The control group was treated
      with conventional hemodialysis, and the treatment group was additionally treated
      with cognitive behavioral therapy for 3 months (sleep-related behavior
      modification and progressive muscle relaxation). All cases were assessed by
      Symptom Checklist 90 (SCL-90) and Pittsburgh Sleep Quality Index (PSQI) before
      and 2, 4, 6, 8, 10, and 12 weeks after treatment. Fifty-one patients in the
      treatment group and 47 patients in the control group completed the experiments.
      After treatment, the total mean scores were (1.94 +/- 0.50/2.29 +/- 0.31); scores
      of somatization, depression, anxiety, hostility, and additional items were (1.87
      +/- 0.58/2.56 +/- 0.26), (2.25 +/- 0.80/2.79 +/- 0.50), (1.79 +/- 0.26/2.37 +/-
      0.34), (1.71 +/- 0.46/2.25 +/- 0.43), and (1.91 +/- 0.67/2.26 +/- 0.59) in SCL
      90, respectively. The total scores for PSQI were (12.63 +/- 2.27/16.40 +/- 2.16);
      scores of subjective sleep quality, sleep latency, sleep duration, habitual sleep
      efficiency, sleep disturbance, hypnotics, and daytime dysfunction which were
      (1.98 +/- 0.76/2.57 +/- 0.58), (1.75 +/- 0.59/2.60 +/- 0.50), (2.10 +/- 0.50/2.62
      +/- 0.53), (2.06 +/- 0.47/2.57 +/- 0.54), (2.04 +/- 0.69/2.45 +/- 0.72), (1.02 +/
      0.79/1.51 +/- 0.98), and (1.69 +/- 0.55/2.09 +/- 0.58), respectively, were
      significantly lower in the treatment group compared with the control group.
      However, there were no significant differences in the scores of factors of
      obsessive-compulsive (2.26 +/- 0.62/2.32 +/- 0.38), interpersonal sensitivity
      (2.23 +/- 0.64/2.43 +/- 0.47), phobic anxiety (1.98 +/- 0.62/2.01 +/- 0.67),
      paranoid ideation (1.55 +/- 0.43/1.69 +/- 0.39), and psychoticism (1.57 +/-
      0.46/1.66 +/- 0.49). The conclusion is that sleep-related behavior modification
      in combination with progressive muscle relaxation effectively improved the mental
      state and sleep quality of MHD patients with insomnia.

PMID- 24577748
TI  - Outcomes of patients with metastatic melanoma treated with immunotherapy prior to
      or after BRAF inhibitors.
AB  - BACKGROUND: The immunotherapy (IT) agents ipilimumab and interleukin-2 as well as
      BRAF inhibitors (BRAFi) vemurafenib and dabrafenib, with or without trametinib
      (MEK inhibitors), are all FDA-approved treatments for BRAF metastatic melanoma,
      but there are few studies to guide optimal sequencing. This retrospective
      analysis describes the outcomes of patients treated with either BRAFi before IT
      or IT before BRAFi. METHODS: A cohort of patients treated with BRAFi alone or
      with MEK inhibitor was retrospectively identified. Response rate (RR), overall
      survival (OS), and progression-free survival (PFS) were evaluated for the entire
      cohort, subdivided by BRAFi prior to or after IT. RESULTS: RR and median PFS and
      OS calculated from commencement of BRAFi following IT (N = 32) were 57%, 6.7
      months (95% confidence interval [CI] = 4.3-9.1 months), and 19.6 months (95% CI =
      10.0-undefined months), respectively; whereas for BRAFi initially (N = 242) were
      66%, 5.6 months (95% CI = 4.7-6.8 months), and 13.4 months (95% CI = 10.1-17.0
      months). Results were similar when controlled for prognostic variables. A total
      of 193 patients discontinued BRAFi, with OS of 2.9 months (range of 1.8-4.4
      months) from day of BRAFi discontinuation. Forty patients subsequently received
      IT with ipilimumab. Only half could complete 4 doses of ipilimumab; PFS with
      ipilimumab was 2.7 months (95% CI = 1.8-3.1 months) and OS was 5.0 months (95% CI
      = 3.0-8.8 months). CONCLUSIONS: In this retrospective analysis, prior treatment
      with IT does not appear to negatively influence response to BRAFi. Outcomes for
      IT with ipilimumab following BRAFi discontinuation are poor. Randomized
      controlled trials are needed to define if sequencing IT prior to BRAFi therapy is
      superior to sequencing BRAFi prior to IT.

PMID- 24577750
TI  - A new approach to designing phase I-II cancer trials for cytotoxic
      chemotherapies.
AB  - Recently, there has been much work on early phase cancer designs that incorporate
      both toxicity and efficacy data, called phase I-II designs because they combine
      elements of both phases. However, they do not explicitly address the phase II
      hypothesis test of H0 : p <= p0 , where p is the probability of efficacy at the
      estimated maximum tolerated dose eta from phase I and p0 is the baseline efficacy
      rate. Standard practice for phase II remains to treat p as a fixed, unknown
      parameter and to use Simon's two-stage design with all patients dosed at eta. We
      propose a phase I-II design that addresses the uncertainty in the estimate
      p=p(eta) in H0 by using sequential generalized likelihood theory. Combining this
      with a phase I design that incorporates efficacy data, the phase I-II design
      provides a common framework that can be used all the way from the first dose of
      phase I through the final accept/reject decision about H0 at the end of phase II,
      utilizing both toxicity and efficacy data throughout. Efficient group sequential
      testing is used in phase II that allows for early stopping to show treatment
      effect or futility. The proposed phase I-II design thus removes the artificial
      barrier between phase I and phase II and fulfills the objectives of searching for
      the maximum tolerated dose and testing if the treatment has an acceptable
      response rate to enter into a phase III trial.

PMID- 24577751
TI  - Chitin synthase A: a novel epidermal development regulation gene in the larvae of
      Bombyx mori.
AB  - Chitin synthase is the key regulatory enzyme for chitin synthesis and excretion
      in insects, as well as a specific target of insecticides. The chitin synthase A
      gene (BmChsA) cloned from Bombyx mori, the model species of lepidopteran, is an
      epidermis-specific expressed gene during the molting stage. Knockdown BmChsA gene
      in 3rd instar larvae increased the number of non-molting and abnormal molting
      larvae. Exposure to nikkomycin Z, a chitin synthase inhibitor downregulated the
      expression of BmChsA and decreased the amount of epidermis chitin during the
      molting process. The thickness of the new epidermis and its dense structure
      varied greatly. The exogenous hormones significantly upregulated the expression
      of BmChsA with low levels of endogenous MH and high levels of endogenous JH
      immediately after molting. With low levels of endogenous hormones during the
      mulberry intake process, BmChsA was rarely upregulated by exogenous hormones.
      With high levels of endogenous MH and low levels of endogenous JH during the
      molting stage, we did not detect the upregulation of BmChsA by exogenous
      hormones. The expression of BmChsA was regulated by endocrine hormones, which
      directly affected the chitin synthesis-dependent epidermal regeneration and
      molting process. 

PMID- 24577753
TI  - Molecular dynamics simulation of the phosphorylation-induced conformational
      changes of a tau peptide fragment.
AB  - Aggregation of the microtubule associated protein tau (MAPT) within neurons of
      the brain is the leading cause of tauopathies such as Alzheimer's disease. MAPT
      is a phospho-protein that is selectively phosphorylated by a number of kinases in
      vivo to perform its biological function. However, it may become pathogenically
      hyperphosphorylated, causing aggregation into paired helical filaments and
      neurofibrillary tangles. The phosphorylation induced conformational change on a
      peptide of MAPT (htau225-250) was investigated by performing molecular dynamics
      simulations with different phosphorylation patterns of the peptide (pThr231
      and/or pSer235) in different simulation conditions to determine the effect of
      ionic strength and phosphate charge. All phosphorylation patterns were found to
      disrupt a nascent terminal beta-sheet pattern (226VAVVR230 and 244QTAPVP249),
      replacing it with a range of structures. The double pThr231/pSer235
      phosphorylation pattern at experimental ionic strength resulted in the best
      agreement with NMR structural characterization, with the observation of a
      transient alpha-helix (239AKSRLQT245). PPII helical conformations were only found
      sporadically throughout the simulations.

PMID- 24577752
TI  - Expression of GLP-1R protein and its clinical role in intrahepatic
      cholangiocarcinoma tissues.
AB  - The study investigates the expression and clinical role of GLP-1R in intrahepatic
      cholangiocarcinoma (ICC) tissues. ICC tissue, tissue around tumour and normal
      liver tissue samples from 176 ICC patients were investigated for GLP-1R
      expression by immunohistochemistry and western blots. Expression levels were
      correlated to clinical variables and to the postoperative outcome. High GLP-1R
      expression levels were detected in tumor tissue samples. Kaplan-Meier method was
      used for survival analysis of patients follow-up data. Results showed that median
      survival time of patients with high GLP-1R positive expression in ICC tissue were
      22 months. Median survival time of patients with low GLP-1R positive expression
      in ICC tissue were 19.8 months. There wasn't statistical difference (p = 0.332)
      between two groups. Immunohistochemistry semi-quantitative analysis showed that
      tissue differentiation is not prognostic risk factors. In patients with GLP-1R
      positive expression in ICC tissue, lymph node metastasis was important prognostic
      factors (p = 0.001). Although statistical analysis showed that GLP-1R can not be
      judged as a risk prognostic factors, GLP-1 might become a new target for therapy
      of ICC.

PMID- 24577754
TI  - Novel bipyridinium ionic liquids as liquid electrochromic devices.
AB  - Novel mono and dialkylbipyridinium (viologens) cations combined with iodide,
      bromide, or bis(trifluoromethanesulfonyl)imide [NTf2] as anions were developed.
      Selective alkylation synthetic methodologies were optimized in order to obtain
      the desired salts in moderate to high yields and higher purities. All prepared
      mono- and dialkylbipyridinium salts were completely characterized by (1)H, (13)C,
      and (19)F NMR spectroscopy, Fourier-transform IR spectroscopy, and elemental
      analysis (in the case of NTf2 salts). Melting points, glass transition
      temperatures by differential scanning calorimetry (DSC) studies, and
      decomposition temperatures were also checked for different prepared organic
      salts. Viscosities at specific temperatures and activation energies were
      determined by rheological studies (including viscosity dependence with
      temperature in heating and cooling processes). Electrochemical studies based on
      cyclic voltammetry (CV), differential pulsed voltammetry (DPV), and square-wave
      voltammetry (SWV) were performed in order to determine the redox potential as
      well as evaluate reversibility behavior of the novel bipyridinium salts. As proof
      of concept, we developed a reversible liquid electrochromic device in the form of
      a U-tube system, the most promising dialkylbipyridinium-NTf2 ionic liquid being
      used as the electrochromic material and the room-temperature ionic liquid (RTIL),
      1-ethyl-3-methylimidazolium bis(trifluoromethanesulfonyl)-imide [EMIM][NTf2], as
      a stable and efficient electrolyte.

PMID- 24577755
TI  - Graphene and graphene-like layered transition metal dichalcogenides in energy
      conversion and storage.
AB  - Being confronted with the energy crisis and environmental problems, the
      exploration of clean and renewable energy materials as well as their devices are
      urgently demanded. Two-dimensional (2D) atomically-thick materials, graphene and
      grpahene-like layered transition metal dichalcogenides (TMDs), have showed vast
      potential as novel energy materials due to their unique physicochemical
      properties. In this Review, we outline the typical application of graphene and
      grpahene-like TMDs in energy conversion and storage fields, and hope to promote
      the development of 2D TMDs in this field through the analysis and comparisons
      with the relatively natural graphene. First, a brief introduction of electronic
      structures and basic properties of graphene and TMDs are presented. Then, we
      summarize the exciting progress of these materials made in both energy conversion
      and storage field including solar cells, electrocatalysis, supercapacitors and
      lithium ions batteries. Finally, the prospects and further developments in these
      exciting fields of graphene and graphene-like TMDs materials are also suggested. 

PMID- 24577756
TI  - The effect of Medicaid on health care consumption of young adults.
AB  - All states provide Medicaid until the age of 19 years. After 19 years, young
      adults may become ineligible for Medicaid. Using the Medical Expenditure Panel
      Survey, we find that the resulting loss of Medicaid coverage causes substantial
      changes to the level and composition of health care use. The total number of
      visits to health care providers falls by over 60%, two-thirds of which is due to
      a decline in office visits. Expenditures, in particular inpatient expenditures,
      also appear to fall sharply.

PMID- 24577759
TI  - [Multidisciplinary therapy for gastric cancer with liver metastasis].
AB  - Gastric cancer with liver metastasis (GCLM) is the leading cause of death in
      patients with advanced gastric cancer. Multiple metastasis was common in GCLM and
      usually complicated with lesions outside the liver, especially peritoneal
      metastasis. Most of liver metastasis lesions could not be resected radically.
      Currently, main treatments for GCLM included radical operation, palliative
      resection of gastric cancer, ablation of metastatic lesions, intervention and
      systemic chemotherapy. Based on the current progress in the treatment for GCLM
      and our clinical experience, the general status of patients, the type of gastric
      cancer and the degree of liver metastasis should be analyzed, and a cooperative
      multidisciplinary team (MDT) should be applied to conduct and to choose active
      and suitable comprehensive treatment for GCLM patients based on individualized
      therapy principle. 

PMID- 24577760
TI  - [Role of surgery in the treatment of liver metastases from gastric cancer].
AB  - The development of liver metastases is a fatal event for gastric cancer patients,
      and remains a major cause of cancer-related death. Many studies showed that the 5
      year survival rate is as low as about 10% in these cases. The management of liver
      metastases from gastric adenocarcinoma remains controversial. The different
      therapeutic modalities used are surgery, radiofrequency ablation, hepatic
      arterial infusion and palliative gastrectomy. Surgery is a good indication for
      single liver metastasis of gastric carcinoma less than 5 cm and not associated
      with another extra-hepatic metastasis. In this article we discuss the role of
      surgery in the treatment of liver metastases from gastric cancer. 

PMID- 24577761
TI  - [Risk factors and prognosis of liver metastasis from gastric cancer].
AB  - Liver metastasis from gastric cancer is a major cause of cancer-related death.
      Since liver metastasis from gastric cancer is usually associated with other non
      curative factors, such as peritoneal metastasis, lymph node metastasis and
      extensive intrahepatic metastasis, the hepatic resection rate was low and the
      prognosis was poor. The main risk factors of liver metastasis were serosal
      invasion, p(+), N3-N4, differentiated histologic type, medullary type of poorly
      differentiated adenocarcinoma, vascular invasion, and overexpression and mutation
      of VEGF, P53 and c-erbb-2. The 5-year survival rate after hepatic resection of
      synchronous and metachronous liver metastasis from gastric cancer ranged from 11%
      to 42%. Appropriate patient selection for hepatic resection may confer a better
      prognosis of liver metastasis from gastric cancer. 

PMID- 24577758
TI  - Hypertension awareness and control among young adults in the national
      longitudinal study of adolescent health.
AB  - BACKGROUND: Young adults are less likely than older adults to be aware they have
      hypertension or to be treated for hypertension. OBJECTIVE: To describe rates of
      hypertension awareness and control in a cohort of young adults and understand the
      impact of health insurance, utilization of preventive care, and self-perception
      of health on rates of hypertension awareness and control in this age group.
      DESIGN AND PARTICIPANTS: Cross-sectional study of 13,512 young adults
      participating in Wave IV of the National Longitudinal Study of Adolescent Health
      in 2007-2008. MAIN MEASURES: We defined hypertension as an average of two
      measured systolic blood pressures (SBP) >= 140 mmHg, diastolic blood pressures
      (DBP) >= 90 mmHg, or self-report of hypertension. We defined hypertension
      awareness as reporting having been told by a health care provider that one had
      high blood pressure, and assessed awareness among those with uncontrolled
      hypertension. We considered those aware of having hypertension controlled if
      their average measured SBP was < 140 mmHg and DBP was < 90 mmHg. KEY RESULTS: Of
      the 3,303 young adults with hypertension, 2,531 (76%) were uncontrolled, and
      1,893 (75%) of those with uncontrolled hypertension were unaware they had
      hypertension. After adjustment for age, sex, race/ethnicity, weight status,
      income, education, alcohol and tobacco use, young adults with uncontrolled
      hypertension who had (vs. didn't have) routine preventive care in the past 2
      years were 2.4 times more likely (95% confidence interval [CI] 1.68-3.55) to be
      aware, but young adults who believed they were in excellent (vs. less than
      excellent) health were 64% less likely to be aware they had hypertension (OR
      0.36, 95% CI 0.23-0.57). Neither preventive care utilization nor self-rated
      health was associated with blood pressure control. CONCLUSIONS: In this
      nationally representative group of young adults, rates of hypertension awareness
      and control were low. Efforts to increase detection of hypertension must address
      young adults' access to preventive care and perception of their need for care.

PMID- 24577762
TI  - [Chemotherapy and targeted therapy in liver metastasis from gastric cancer].
AB  - Gastric cancer remains one of the most common malignancies and leading causes of
      cancer death in China with a complex biological behavior. The incidence of liver
      metastasis from gastric cancer is particularly high. The indication of
      hepatectomy is controversial, however, surgery should be considered. How to
      choose the right regimen to obtain macroscopically complete resections represents
      a controversial subject. Newer generation cytotoxic agents such as docetaxel, S-1
      and irinotecan as well as targeted therapy agent trastuzumab exhibit promising
      activity in gastric cancer. Further study and clinical trials are needed to
      confirm the benefits of systemic treatment in gastric cancer patients with liver
      metastasis. 

PMID- 24577763
TI  - [Comparison of clinical efficacy of different treatment methods for synchronous
      liver metastasis from gastric cancer].
AB  - OBJECTIVE: To evaluate the efficacy of different treatments for synchronous liver
      metastasis from gastric cancer. METHODS: Clinicopathological and follow-up data
      of 271 patients with synchronous liver metastasis from gastric cancer between
      January 1998 and November 2012 were analyzed retrospectively. Among 271 patients,
      34 received surgery alone, 95 received chemotherapy alone, and 120 received
      combined therapy. The prognosis was compared. RESULTS: The median survival time
      was 8 months (3-41 months) in the surgery group and the cumulative 1-, 3- and 5
      year survival rates were 32.4%, 2.9% and 0. The median survival time was 7 months
      (3-50 months) in the chemotherapy group and the cumulative 1-, 3- and 5-year
      survival rates were 21.1%, 1.1% and 0 respectively. The median survival time was
      11 months (3-84 months) in the combined group and the cumulative 1-, 3- and 5
      year survival rates were 50.0%, 5.0% and 0.8% respectively. The differences among
      groups were all statistically significant (all P<0.05). Extent of lymph node
      metastasis, therapeutic strategies, and liver metastasis management were
      significantly independent prognostic factors for synchronous liver metastasis
      from gastric cancer. CONCLUSIONS: Comprehensive treatment based on operation may
      improve the long-term survival of patients with synchronous liver metastasis from
      gastric cancer.

PMID- 24577764
TI  - [Risk factors in metachronous liver metastasis from gastric cancer].
AB  - OBJECTIVE: To explore the clinicopathological characteristics and related risk
      factors in metachronous liver metastasis of gastric cancer. METHODS: Clinical
      data of 115 patients with metachronous liver metastasis in Tianjin Medical
      University Cancer Institute and Hospital between 1996 and 2008 were analyzed
      retrospectively. RESULTS: Among 115 patients, the 1-, 3- and 5-year non-hepatic
      metastasis rates were 45.3%, 14.8% and 3.5% respectively. Univariate Log-rank
      test indicated that location, tumor size, tumor differentiation, depth of
      invasion, lymph node metastasis, vascular invasion, nervous invasion, soft tissue
      invasion, and modes of gastrectomy were significant factors associated with
      hepatic metastasis after radical gastrectomy. On multivariate analysis, the size
      of gastric cancer, vascular invasion, tumor differentiation, and lymph node
      metastasis were independent factors associated with metachronous liver metastasis
      of gastric cancer. CONCLUSIONS: The size of gastric cancer, vascular invasion,
      tumor differentiation and lymph node metastasis are important factors associated
      with the risk of hepatic metastasis from gastric cancer in patients after radical
      gastrectomy.

PMID- 24577765
TI  - [Prognostic analysis of patients with synchronous liver metastasis from gastric
      cancer following simultaneous gastric and liver resection].
AB  - OBJECTIVE: To investigate the surgical results of hepatic resection for solitary
      metastasis form gastric cancer. METHODS: Clinical data of 53 patients who
      underwent simultaneous curative gastric and liver resection in our hospital from
      January 1998 to December 2012 were analyzed retrospectively. Univariate and
      multivariate analyses were performed to examine independent factors for survival.
      RESULTS: In 53 patients, the accumulated 5-year survival rate after hepatic
      resection was 11.3%, 14.7% for solitary metastasis and 0 for multiple metastases.
      The statistically significant prognostic factors affecting 5-year survival rates
      were found to be serosal invasion (P=0.000), lymph node metastasis (P=0.000), the
      degree of radical resection (P=0.044), number of hepatic metastases (P=0.000),
      liver metastasis size (P=0.031). Multivariate Cox regression analysis showed that
      the serosal invasion (RR:3.355, P=0.012) and number of hepatic metastasis
      (RR:7.664, P=0.000) were independent prognostic factors in patients with liver
      metastasis from gastric cancer. CONCLUSION: The prognosis of solitary metastasis
      from gastric cancer without serosal invasion can be improved through active
      radical resection based on suitable indications.

PMID- 24577766
TI  - [Meta-analysis of prognosis after surgical treatment in gastric cancer patients
      with liver metastasis].
AB  - OBJECTIVE: To assess the value of gastric and hepatic surgical treatment in
      gastric cancer patients with liver metastasis and its prognostic implication.
      METHODS: Literature search was performed in pubmed, Embase, Ovid, Springer-Link,
      Web of Science, CNKI, CBMdisc for clinical research published before March 2013
      that compared gastrectomy alone to gastrectomy and hepatectomy. Inclusion
      criteria and exclusion criteria were performed. Quality assessment was based on
      NOS scale. Stata12.0 was used for statistical analysis. RESULTS: Nine studies
      including 431 patients were enrolled for analysis, among whom 189 underwent
      gastrectomy and hepatectomy and 242 underwent gastrectomy alone. Gastrectomy and
      hepatectomy group had better survival(HR=0.50, 95%CI:0.34-0.72, z=3.66, P=0.000).
      There was a subgroup analysis. Gastrectomy with hepatectomy group had significant
      advantages in prognosis in four foreign studies(HR=0.28, 95%CI:0.18-0.44, z=5.77,
      P=0.000). There was no significant difference in five domestic studies (HR=0.74,
      95%CI:0.55-1.00, z=1.95, P=0.051). CONCLUSION: Gastrectomy and hepatectomy in
      gastric cancer patients with liver metastasis improves long-term survival in
      select patients.

PMID- 24577767
TI  - [Adjuvant capecitabine and oxaliplatin for gastric cancer after D2 gastrectomy
      (CLASSIC): Chinese subgroup analysis].
AB  - OBJECTIVE: To evaluate the efficacy and safety profile of XELOX
      (capecitabine/oxaliplatin) in patients with locally advanced gastric cancer who
      underwent curative D2 resection in China. METHODS: This is a subgroup analysis of
      Chinese patients in the capecitabine and oxaliplatin adjuvant study in stomach
      cancer (CLASSIC study), which was a randomised, open-label, multicentre, parallel
      group, phase III( study in the Asia-Pacific region. A total of 100 gastric cancer
      patients who received curative D2 gastrectomy were enrolled in this study and
      were randomly assigned to either XELOX group (oral capecitabine combined with
      intravenous oxaliplatin chemotherapy) or the control group (surgery alone). This
      study aims to compare the 3-year disease-free between the two groups. RESULTS:
      Subgroup analysis showed that 3-year DFS rate were 78% and 56% in XELOX and
      control group, respectively. The risk of relapse in XELOX group was reduced by
      59% (HR=0.41, 95%CI:0.20-0.85, P=0.013), compared with the control group. The 3
      year overall survival rate were 78% and 66% in XELOX and control group, with no
      statistically significant difference (HR=0.55, 95%CI:0.26-1.16, P=0.110).
      CONCLUSION: Adjuvant XELOX chemotherapy following D2 gastrectomy may improve the
      survival in patients with advanced gastric cancer in China.

PMID- 24577768
TI  - [Changes in clinicopathological features and survival after surgical resection
      for gastric cancer over a 20-year period at a single institution].
AB  - OBJECTIVE: To investigate changes in clinicopathological features and survival of
      patients with gastrectomy at a single institution in China. METHODS: From January
      1990 to December 2009, clinicopathological data of 2518 cases of gastric cancer
      patients who underwent surgical resection in the Sun Yat-sen University Cancer
      Center were analyzed retrospectively. The overall survival rate was determined
      using Kaplan-Meier method and log-rank test was used to determine significance.
      The prognosis was analyzed using univariate analysis and multivariate analysis by
      Cox proportional hazards model. Clinical features, pathological findings and
      survival differences were compared in this cohort between two consecutive
      periods(1990-1999 and 2000-2009). RESULTS: The 5-year survival rates for the
      whole cohort and those undergoing radical resection was 48.1% and 53.7%,
      respectively. In the first period, the 5-year survival rate for the whole cohort
      and for patients undergoing radical resection was 40.1% and 45.7%. In the second
      period, the 5-year survival rates for whole cohort and for patients undergoing
      radical resection was 51.5% and 57.1%, respectively. For those who underwent
      radical resection, the mean number of lymph node dissection was significantly
      higher in the recent period (20.1+/-8.3 vs. 9.5+/-6.0, P<0.01). On multivariate
      analysis by means of the Cox proportional hazard model, age, location, tumor
      size, histological type, radical resection, lymphatic/venous invasion, depth of
      invasion, nodal status, number of retrieved lymph nodes, and treatment period
      were independent factors (P<0.05). The constitution, number of retrieved lymph
      nodes, and survival rate were all improved between the two intervals (P<0.05).
      CONCLUSION: The overall survival rate has gradually increased in gastric cancer
      patients over the past 20 years.

PMID- 24577769
TI  - [Evaluation of lymphatic emboli in gastric cancer by D2-40/CKpan dual immunostain
      and its significance].
AB  - OBJECTIVE: To investigate the evaluation of lymphatic emboli by D2-40/CKpan dual
      immunostain and its prognostic significance in advanced primary gastric
      adenocarcinoma. METHODS: Tissue samples of 108 cases of advanced gastric
      adenocarcinoma with radical gastrectomy were collected from Chinese PLA General
      Hospital in 2001. Lymphatic emboli were evaluated by D2-40/CKpan dual immunostain
      on consecutive sections, and compared with routine HE staining. The correlation
      of lymphatic emboli with lymph node metastasis and overall survival was analyzed
      by Pearson Chi-squared test and univariate survival analysis, respectively.
      RESULTS: Lymphatic emboli were detected in 73/108 (67.6%) cases by D2-40/CKpan
      staining, compared to 57/108 (52.8%) by HE staining. There was significant
      difference (P=0.007). Lymphatic emboli on HE staining revealed false negative in
      24/108 cases and false positive in 8/108 cases. A significant correlation was
      found between lymphatic emboli and lymph node metastasis on HE staining
      (P=0.024), while it was not found on D2-40/CKpan staining (P=0.422). The overall
      survival rate was significantly different between lymphatic emboli positive and
      negative cases on HE staining (P=0.043). The overall survival rate was lower in
      lymphatic emboli positive cases on HE staining. Lymphatic emboli evaluated on D2
      40/CKpan staining had no prognostic value (P=0.402). CONCLUSION: D2-40/Ckpan dual
      immunostaining is more sensitive for lymphatic emboli in gastric adenocarcinoma
      but may not predict lymph node metastasis and survival, while HE staining may.

PMID- 24577770
TI  - [Advanced adenocarcinoma and concurrent mucosa-associated lymphoid tissue
      lymphoma of the stomach: a case report and literature review].
AB  - OBJECTIVE: To investigate the clinical and pathological features of patients with
      concurrent gastric adenocarcinoma and primary gastric mucosa-associated lymphoid
      tissue (MALT) lymphoma. METHODS: A 77-year-old man referred to Beijing Cancer
      Hospital for the evaluation of two primary cancers of stomach revealed by
      gastroscope was reported. The English literature was retrieved and analyzed.
      RESULTS: Total gastrectomy was performed. Histological examination confirmed that
      the gastric body lesion was consistent with advanced poorly differentiated
      adenocarcinoma, while the lesion at the fundus with low grade MALT lymphoma. A
      systematic review of literature in English was performed, and 40 similar patients
      from 12 studies were found. There were 25 males(61.0%). More patients with
      adenocarcinoma were at early stage (65.9%) and the majority of lymphoma was low
      grade (82.9%). Furthermore, most of the patients experienced Helicobacter pylori
      infection (72.5%). As for therapeutic strategy, most of the patients underwent
      subtotal or total gastrectomy. CONCLUSIONS: Concurrent gastric adenocarcinoma
      with MALT lymphoma is rare. The characteristics of these tumors are still
      unclear. The majority of gastric adenocarcinoma is at early stage, and most of
      the patients have Helicobacter pylori infection. The treatment is mainly based on
      gastric adenocarcinoma.

PMID- 24577771
TI  - [Analysis of risk factors associated with metastasis of lymph node along superior
      mesenteric vein in patients with gastric cancer].
AB  - OBJECTIVE: To investigate the risk factors associated with metastasis of lymph
      node along superior mesenteric vein (No.14v) in gastric cancer. METHODS:
      Clinicopathological data of 70 gastric cancer patients undergoing gastrectomy
      with No.14v dissection between September 2010 and October 2011 in the Gulou
      Hospital, Nanjing University School of Medicine were analyzed retrospectively.
      Associated factors of No.14v lymph nodes metastasis were investigated. RESULTS:
      Of 70 cases, positive No.14v lymph node metastasis was found in 8 cases (11.4%).
      Univariate analysis showed that the No.14v metastasis was associated with tumor
      location (P=0.019), tumor size (P=0.004), depth of invasion (P=0.001), TNM
      staging (P=0.006), and other lymph node group metastasis (all P<0.05), and was
      not associated with age, gender, Borrmann classification, Lauren classification
      or histological type (all P>0.05). Multivariate analysis revealed that lntra
      pyloric lymph nodes (No.6) metastasis was an independent risk factor of No.14v
      metastasis (P<0.05). The predictive accuracy was 94.3% (66/70) and false-negative
      rate was 1.7% (1/60) for No.6 lymph node metastasis. CONCLUSION: No.6 lymph node
      metastasis status can predict the metastasis of No.14v more accurately.

PMID- 24577772
TI  - [Application of home enteral nutrition and its impact on the quality of life in
      patients with advanced gastric cancer].
AB  - OBJECTIVE: To investigate the application of home enteral nutrition (HEN) in
      patients with advanced gastric cancer and its impact on the quality of life.
      METHODS: Data of 60 consecutive patients with advanced gastric cancer, who could
      not underwent operation and had relapse metastasis, from June 2010 to June 2012
      were retrospectively analyzed. According to familial nutritional pattern, these
      60 patients were divided into HEN group (25 cases) receiving home enteral
      nutritional support and control group (35 cases). HEN patients were supported
      through jejunostomy tube or nasal gastric tube. Control patients were supported
      through total parental nutrition or purely eating respectively. All the patients
      received intravenous chemotherapy and evaluated by Karnofsky index and Spitzer
      system in the first, third, sixth and twelfth month. In the sixth month, patients
      were also examined by EORTC QLQ-C30. RESULTS: No significant differences were
      found between the two groups according to 8 elements containing age, sex, BMI,
      etc. A total of 53 patients died within one year, including 21 in HEN group and
      32 in control group. The Karnofsky scales showed that HEN group scored meanly
      57.4, 39.6 and 28.2 in the third, sixth and twelfth month respectively, which
      were significantly higher than those of control group (45.3, 29.2 and 20.1,
      P=0.041, P=0.012 and P=0.015 respectively). The Spitzer scales showed that HEN
      group scored meanly 5.12, 4.04 and 2.54 on average in the third, sixth and
      twelfth month respectively, which were significantly higher than those of control
      group (4.32, 3.01 and 1.97, P=0.048, 0.035 and P=0.024 respectively). The EROTC
      QLQ-C30 scales showed that HEN group scored higher than control group in
      functional scales (P<0.05), and lower in the symptom scales of short breathing,
      pain and tired (P=0.025, P=0.044, P=0.036 respectively), while higher in diarrhea
      (P=0.047). CONCLUSIONS: The quality of life of patients with advanced gastric
      cancer declines gradually with the nutritional status deteriorating. HEN can be
      applied to improve the nutritional status and quality of life.

PMID- 24577773
TI  - [Impact of different pneumoperitioneal pressure on pathomorphism and function of
      intestines following laparoscopic radical gastrectomy].
AB  - OBJECTIVE: To investigate the influence of different pressures of CO2
      pneumoperitioneum on pathomorphism and function of intestines following
      laparoscopic gastrectomy (LG). METHODS: Forty-eight gastric cancer patients were
      prospectively enrolled in the study. Among them, 36 patients scheduled for
      elective LG were randomly assigned to low pressure group (LP), middle pressure
      (MP), and high pressure group (HP) with 12 cases in each group. The CO2
      pneumoperitoneum pressure was maintained at 8-10 mmhg in LP, 11-13 mmhg in MP,
      and 14-16 mmhg in HP. The control group was open gastrectomy group (OG) in 12
      cases. The intestinal pathomorphism and level of plasma D-lactic acid before,
      during and after operation, and postoperative intestinal function of four groups
      were examined and compared. RESULTS: There were no statistical differences in
      preoperative data among the four groups(all P>0.05). LG group was associated with
      a lower rate of surgical complications than OG (8.3% vs. 41.7%, P<0.05). No
      obvious damage of intestinal mucosa was found in OG group. Damage degree of
      intestinal mucosa after operation in LP, MP and HP groups was 0-1, 1-2, and 2-3
      respectively. There was significant change in intestinal pathomorphism after
      operation in both HP and MP groups. The levels of D-lactic acid before operation
      were not significantly different among all the four groups, but increased
      significantly in each group after operation (all P<0.05). HP group had the
      highest level of plasma D-lactic acid and presented with delayed bowel sound
      return (4.5 d), time to first flatus (5.4 d), and intake (6.0 d) as compared to
      the other 3 groups (all P<0.05). CONCLUSIONS: Laparoscopic radical gastrectomy is
      safe and minimally invasive. Higher pneumoperitoneal pressure is harmful to the
      recovery of intestinal mucosa and function. Therefore the pneumoperitioneum
      pressure should be maintained as low as possible under clear visualization during
      operation.

PMID- 24577774
TI  - [Relationship between CD133 and chemoresistance in human gastric cancer and its
      associated mechanism].
AB  - OBJECTIVE: To explore the relationship between CD133(+) subsets cells in human
      gastric cancer (GC) and molecules of drug resistance and their sensitivity to 5
      FU. METHODS: Three gastric cancer cell lines therein KATO-III(, SGC7901 and MKN45
      were sorted by immunomagnetic beads cell sorting method. Then above cell lines
      were further divided into un-sorted GC cells, CD133(+) subgroup and CD133(-)
      subgroup. The expressions of CD133, P-gp, Bax and Bcl-2 were determined by RT
      PCR, Western blot and immunoflurescence. Meanwhile, the sensitivity to 5-FU of
      three subgroups was detected by CCK-8 Kit. The apoptosis induced by 5-FU in three
      subgroups was determined by Hoechst 33258. RESULTS: Expressions of CD133 in three
      CD133(+) subgroups were significantly higher than those in un-sorted GC cells and
      CD133(-) subgroup (all P<0.05). Expressions of P-gp and Bcl-2 in the three GC
      cell lines were different (all P<0.05). There were significant differences of
      expressions of P-gp, Bcl-2 and Bax among CD133(+) cells, un-sorted GC cells and
      CD133(-) cells (all P<0.05). CCK-8 detection showed that CD133(-) subgroup of
      MKN45 GC cell line was more sensitive than CD133(+) cells to 5-FU (P<0.05).
      Hoechst 33258 staining showed that there were more apoptotic cells in CD133(-)
      subgroup as compared to other two subgroups, and the least apoptotic cells were
      observed in CD133(+) subgroup of MKN45 GC cell line (P<0.05). CD133 sirna was
      transfected into MKN45 GC cell line and could down-regulate the expressions of
      CD133, P-gp, Bcl-2 and p-Akt, while the expression of Bax increased (all P<0.05).
      CONCLUSIONS: CD133 may contribute to the resistance of GC cells to chemotherapy
      drug through P-gp, Bcl-2 and Bax. PI3K/Akt signal pathway may be involved in this
      process.

PMID- 24577775
TI  - [Screening of specific miRNA in early gastric cancer].
AB  - OBJECTIVE: To examine the micro-RNA (mirna) expression profile in tissues of
      early gastric cancer and to screen the specific mirna associated with gastric
      cancer. METHODS: Gene chip technology was used to detect the expression of mirna
      in early gastric cancer tissues and adjacent normal tissues. RESULTS: Compared to
      adjacent normal tissues, a total of 36 mirnas were down-regulated, such as mir-9
      1, mir-103 and mir-141, while 12 mirnas were up-regulated, such as mir-196a, mir
      142-3p and mir-25, etc. CONCLUSION: Abnormal mirna expression level in early
      gastric cancer tissues may be associated to the development of gastric cancer.

PMID- 24577776
TI  - [Anatomy of the perigastric vessels in laparoscopy-assisted distal gastrectomy
      with D2 lymphadenectomy for gastric cancer].
AB  - The laparoscopic approach is rapidly becoming the preferred method of treatment
      for patients with early gastric cancer due to advantages of minimally invasive
      surgery. As laparoscopic experience has accumulated, laparoscopy-assisted distal
      gastrectomy (LADG) with D2 lymphadenectomy has become a valuable alternative for
      the treatment of patients with advanced gastric cancer. However, laparoscopic
      gastric surgery is demanding from a technical point of view, especially when a D2
      lymphadenectomy is performed. Surgeons seeking to undertake LADG are concerned
      about unpredictable intraoperative bleeding that may occur during LADG.
      Comprehensive knowledge of the perigastric vascular anatomy is essential for LADG
      with D2 lymphadenectomy. 

PMID- 24577777
TI  - [Research progression of translational medicine in gastric cancer].
AB  - Gastric cancer is one of the most common malignant tumors which is a great threat
      to human health. In recent years, the reform of surgical mordalities and the
      optimization of radiation and chemotherapy is still far from reducing morbidity
      and mortality of gastric cancer. As a new research pattern, translational
      medicine has emerged in various clinical subjects, which leads to remarkable
      effects. In this paper, the definition and development of translational medicine,
      molecular markers and drug treatment of gastric cancer will be discussed and the
      feasibility of translational medicine in the treatment of gastric cancer will be
      explained. In our opinion, the intervention of translational medicine could
      change the current situation that scientific researches is severely disconnected
      with clinical practice and increase the detection rate of gastric cancer and the
      effective rate of adjuvant therapy after surgery to improve the prognosis of
      patients with gastric cancer. 

PMID- 24577778
TI  - [Clinical characteristics and prognosis of hepatoid adenocarcinoma of the
      stomach].
AB  - Hepatoid adenocarcinoma of the stomach (HAS) is a special type of gastric cancer
      characterized with hepatoid differentiation and the production of large amounts
      of alpha-fetoprotein (AFP). The pathogenesis of HAS is still not clear. Most of
      the relative studies are single case reports, and studies with large sample are
      absent. The prognosis of HAS is poor. HAS has a high rate of liver metastasis.
      The biology behaviors of HAS differ from common gastric cancers. Radical
      resection of the gastric cancer is considered to be the main treatment when no
      liver metastasis is found, while the treatment regimens of the metastasis lesions
      are still in debate. The serum AFP test is important for the early detection and
      diagnosis of HAS, and it is crucial for monitoring the therapeutic effect and the
      relapse and metastasis of the tumor. 

PMID- 24577780
TI  - Self-reported moderate-to-vigorous leisure time physical activity predicts less
      pain and disability over 12 months in chronic and persistent low back pain.
AB  - BACKGROUND: Physical deconditioning in combination with societal and emotional
      factors has been hypothesized to compromise complete recovery from low back pain
      (LBP). However, there is a lack of longitudinal studies designed to specifically
      investigate physical activity as an independent prognostic factor. We conducted a
      prognostic study to investigate whether levels of leisure time physical activity
      are independently associated with clinical outcomes in people seeking care for
      chronic and persistent LBP. METHODS: A total of 815 consecutive patients
      presenting with LBP to an outpatient spine centre in secondary care were
      recruited. Separate multivariate linear regression analyses were performed to
      investigate whether levels of leisure time physical activity (i.e., sedentary,
      light and moderate-to-vigorous leisure time physical activity levels) predict
      pain and disability at 12-month follow-up, after adjusting for age, pain, episode
      duration, disability, neurological symptoms, depression and fear of movement.
      RESULTS: Final models showed evidence of an association between baseline physical
      activity and 12-month outcomes (p < 0.001). In both models, the moderate-to
      vigorous physical activity group reported less pain and disability compared with
      the sedentary group. CONCLUSIONS: Our findings suggest that physical activity
      levels may have a role in the prognosis of LBP. Specific domains of physical
      activity warrant further investigation to better understand this association.

PMID- 24577781
TI  - Following through: the consistency of survivorship care plan use in United States
      cancer programs.
AB  - The Institute of Medicine suggests that consistent survivorship care plan (SCP)
      use involves developing and delivering SCPs to all cancer survivors and their
      primary care providers (PCPs). We describe the consistency of SCP use in US
      cancer programs and assess its relationship with cancer-program-level
      determinants. We surveyed employees knowledgeable about survivorship practices in
      cancer programs reporting current SCP use (n = 36, 81 % response rate). We
      operationalized consistent SCP use as whether SCPs were (1) developed for >=75 %
      survivors, (2) delivered to >=75 % survivors, (3) delivered to >=75 % PCPs, and
      (4) all of the above. We use descriptive statistics to report SCP use consistency
      and evaluate associations using Fisher's exact and Wilcoxon rank sum tests. SCPs
      were developed for >=75 % survivors in five programs (15 %), eight (25 %)
      delivered >=75 % SCPs to survivors, seven (23 %) delivered >=75 % SCPs to PCPs,
      and only one program (4 %) met all three criteria. We found relationships between
      SCP use consistency and geographic region (p = .05), initiating SCP use in
      response to survivors' requests (p = .03), and membership in the National Cancer
      Institute's National Community Cancer Centers Program (p = .01). SCP use is
      highly inconsistent. Survivors and cancer care quality improvement organizations
      may play a key role in improving the consistency of SCP use in US cancer
      programs. Survivors can initiate SCP use. Cancer care quality improvement
      organizations can specify how cancer programs' compliance with SCP guidelines
      will be assessed. Future research should identify mechanisms underlying the
      relationships that we found.

PMID- 24577782
TI  - Ships passing in the night : opportunities for cancer education.

PMID- 24577784
TI  - Characterization of a bacterial tannase from Streptococcus gallolyticus UCN34
      suitable for tannin biodegradation.
AB  - The gene in the locus GALLO_1609 from Streptococcus gallolyticus UCN34 was cloned
      and expressed as an active protein in Escherichia coli BL21 (DE3). The protein
      was named TanSg1 since it shows similarity to bacterial tannases previously
      described. The recombinant strain produced His-tagged TanSg1 which was purified
      by affinity chromatography. Purified TanSg1 protein showed tannase activity,
      having a specific activity of 577 U/mg which is 41 % higher than the activity of
      Lactobacillus plantarum tannase. Remarkably, TanSg1 displayed optimum catalytic
      activity at pH 6-8 and 50-70  degrees C and showed high stability over a broad
      range of temperatures. It retained 25 % of its relative activity after prolonged
      incubation at 45  degrees C. The specific activity of TanSg1 is enhanced by the
      divalent cation Ca(2+) and is dramatically reduced by Zn(2+) and Hg(2+). The
      enzyme was highly specific for gallate and protocatechuate esters and showed no
      catalytic activity against other phenolic esters. The protein TanSg1 hydrolyzes
      efficiently tannic acid, a complex and polymeric gallotanin, allowing its
      complete conversion to gallic acid, a potent antioxidant. From its biochemical
      properties, TanSg1 is a tannase with potential industrial interest regarding the
      biodegradation of tannin waste or its bioconversion into biologically active
      products.

PMID- 24577783
TI  - Polyubiquitinated proteins, proteasome, and glycogen characterize the particle
      rich cytoplasmic structure (PaCS) of neoplastic and fetal cells.
AB  - A particle-rich cytoplasmic structure (PaCS) concentrating ubiquitin-proteasome
      system (UPS) components and barrel-like particles in clear, cytoskeleton- and
      organelle-free areas has recently been described in some neoplasms and in genetic
      or infectious diseases at risk of neoplasia. Ultrastructurally similar
      particulate cytoplasmic structures, interpreted as glycogen deposits, have
      previously been reported in clear-cell neoplasms and some fetal tissues. It
      remains to be investigated whether the two structures are the same, colocalize
      UPS components and polysaccharides, and have a role in highly proliferative cells
      such as fetal and neoplastic cells. We used immunogold electron microscopy and
      confocal immunofluorescence microscopy to examine human and mouse fetal tissues
      and human neoplasms. Fetal and neoplastic cells both showed colocalization of
      polyubiquitinated proteins, 19S and 20S proteasomes, and polysaccharides, both
      glycogen and chondroitin sulfate, inside cytoplasmic structures showing all
      distinctive features of PaCSs. Poorly demarcated and/or hybrid (ribosomes
      admixed) UPS- and glycogen-enriched areas, likely stages in PaCS development,
      were also seen in some fetal cells, with special reference to those, like primary
      alveolar pulmonary cells or pancreatic centroacinar cells, having a crucial role
      in organogenesis. UPS- and glycogen-rich PaCSs developed extensively in clear
      cell neoplasms of the kidney, ovary, pancreas, and other organs, as well as, in
      infantile, development-related tumors replicating fetal patterns, such as choroid
      plexus papilloma. UPS-mediated, ATP-dependent proteolysis and its potential
      energy source, glycogen metabolism, may have a crucial, synergic role in embryo
      /organogenesis and carcinogenesis. 

PMID- 24577785
TI  - A systematic review of people with autism spectrum disorder and the criminal
      justice system.
AB  - This paper provides a systemic review of the available literature on people with
      autism spectrum disorder (ASD) in the criminal justice system (CJS). The review
      considers two main types of study: those that examined the prevalence of people
      with ASD in the CJS and those that examined the prevalence of offending in
      populations with ASD. In addition, types of offences in people with ASD, co
      morbid psychiatric diagnoses, and characteristics of people with ASD who commit
      offences (including predisposing factors) are considered. A combination of search
      terms was used in a variety of databases in order to find all of the available
      literature on this topic, and research studies were included based on specified
      inclusion and exclusion criteria. It was found that whilst there is an emerging
      literature base on this topic, there are a wide variety of methodologies used,
      making direct comparison difficult. Nevertheless it can be concluded so far that
      people with ASD do not seem to be disproportionately over-represented in the CJS,
      though they commit a range of crimes and seem to have a number of predisposing
      features. There is poor evidence of the presence of comorbid psychiatric
      diagnoses (except in mental health settings) amongst offenders with ASD, and
      little evidence of the oft-asserted over-representation of certain kinds of
      crimes. It is recommended that further research of good quality is required in
      this area, rather than studies that examine populations that are not
      representative of all those with ASD. 

PMID- 24577787
TI  - Relationship between physician preference for infusion therapies and financial
      considerations: comment on the article by Zhang et al.

PMID- 24577786
TI  - Caring for a child with autism spectrum disorder and parents' quality of life:
      application of the CarerQol.
AB  - This study describes the impact of caregiving on parents of children with autism
      spectrum disorders (ASDs). Secondly, we investigate construct validation of the
      care-related quality of life instrument (CarerQol) measuring impact of
      caregiving. Primary caregivers of children with ASDs were included. Many parents
      experienced considerable problems combining daily activities with care, had
      financial problems or suffered from depressive mood. Validity tests showed that a
      higher impact of caring on the CarerQol was positively associated with higher
      subjective burden and lower family quality of life. Most of the associations
      between CarerQol scores and background characteristics confirmed previous
      research. The CarerQol validly measures the impact of caregiving for children
      with ASDs on caregivers in our sample. The CarerQol may therefore be useful for
      including parent outcomes in research on ASDs. 

PMID- 24577788
TI  - Ipilimumab before BRAF inhibitor treatment may be more beneficial than vice versa
      for the majority of patients with advanced melanoma.

PMID- 24577789
TI  - The dissipation of carbofuran in two soils with different pesticide application
      histories within Nzoia River Drainage Basin, Kenya.
AB  - The dissipation of carbofuran from soils within the Nzoia River Drainage Basin in
      Kenya was studied under real field conditions for 112 days. Results showed
      significantly enhanced dissipation of carbofuran with half life (DT50) values of
      8 days (p = 0.038) in soils with prior exposure to carbofuran compared to 19 days
      in soils with no application history. At the end of the experiment, residues of
      2.57% and 9.36% of the initial carbofuran applied were recorded in the two types
      of soil, respectively. Carbofuran metabolites identified in the study were 3-keto
      carbofuran and carbofuran phenol with 5.84% and 15.0% remaining in soils with
      prior exposure, respectively. Soils with no application history recorded 16.05%
      and 12.82% of 3-keto carbofuran and carbofuran phenol metabolites, respectively.

PMID- 24577791
TI  - Pluripotent stem cells as a potential tool for disease modelling and cell therapy
      in diabetes.
AB  - Diabetes mellitus is the most prevailing disease with progressive incidence
      worldwide. To date, the pathogenesis of diabetes is far to be understood, and
      there is no permanent treatment available for diabetes. One of the promising
      approaches to understand and cure diabetes is to use pluripotent stem cells
      (PSCs), including embryonic stem cells (ESCs) and induced PCSs (iPSCs). ESCs and
      iPSCs have a great potential to differentiate into all cell types, and they have
      a high ability to differentiate into insulin-secreting beta cells. Obtaining PSCs
      genetically identical to the patient presenting with diabetes has been a
      longstanding dream for the in vitro modeling of disease and ultimately cell
      therapy. For several years, somatic cell nuclear transfer (SCNT) was the method
      of choice to generate patient-specific ESC lines. However, this technology faces
      ethical and practical concerns. Interestingly, the recently established iPSC
      technology overcomes the major problems of other stem cell types including the
      lack of ethical concern and no risk of immune rejection. Several iPSC lines have
      been recently generated from patients with different types of diabetes, and most
      of these cell lines are able to differentiate into insulin-secreting beta cells.
      In this review, we summarize recent advances in the differentiation of pancreatic
      beta cells from PSCs, and describe the challenges for their clinical use in
      diabetes cell therapy. Furthermore, we discuss the potential use of patient
      specific PSCs as an in vitro model, providing new insights into the
      pathophysiology of diabetes. 

PMID- 24577790
TI  - Therapeutic application of adipose derived stem cells in acute myocardial
      infarction: lessons from animal models.
AB  - The majority of patients survive an acute myocardial infarction (AMI). Their
      outcome is negatively influenced by post-AMI events, such as loss of viable
      cardiomyocytes due to a post-AMI inflammatory response, eventually resulting in
      heart failure and/or death. Recent pre-clinical animal studies indicate that
      mesenchymal stem cells derived from adipose tissue (ASC) are new promising
      candidates that may facilitate cardiovascular regeneration in the infarcted
      myocardium. In this review we have compared all animal studies in which ASC were
      used as a therapy post-AMI and have focused on aspects that might be important
      for future successful clinical application of ASC. 

PMID- 24577792
TI  - Testing for efficacy in adaptive clinical trials with enrichment.
AB  - Adaptive design of clinical trials has attracted considerable interest because of
      its potential of reducing costs and saving time in the clinical development
      process. In this paper, we consider the problem of assessing the effectiveness of
      a test treatment over a control by a two-arm randomized clinical trial in a
      potentially heterogenous patient population. In particular, we study enrichment
      designs that use accumulating data from a clinical trial to adaptively determine
      patient subpopulation in which the treatment effect is eventually assessed. A
      hypothesis testing procedure and a lower confidence limit are presented for the
      treatment effect in the selected patient subgroups. The performances of the new
      methods are compared with existing approaches through a simulation study.

PMID- 24577793
TI  - Sporothrix schenckii sensu stricto isolated from soil in an armadillo's burrow.
AB  - Sporotrichosis is a polymorphic disease of man and animals caused by traumatic
      implantation of propagules into the skin and subcutaneous tissue. Pathogenic
      species includes S. brasiliensis, S. schenckii, S. globosa and S. luriei. The
      disease is remarkable for its occurrence as sapronoses and/or zoonosis outbreaks
      in tropical and subtropical areas; although, the ecology of the clinical clade is
      still puzzling. Here, we describe an anamorphic Sporothrix strain isolated from
      soil in an armadillo's burrow, which was located in a hyper endemic area of
      Paracoccidioidomycosis in Brazil. This isolate was identified as S. schenckii
      sensu stricto (Clade IIa) based on morphological and physiological
      characteristics and phylogenetic analyses of calmodulin sequences. We then
      discuss the role of the nine-banded armadillo Dasypus novemcinctus as a natural
      carrier of Sporothrix propagules to better understand Sporothrix sources in
      nature and reveal essential aspects about the pathogen's eco-epidemiology. 

PMID- 24577795
TI  - Tumor-targeting multifunctional nanoparticles for siRNA delivery: recent advances
      in cancer therapy.
AB  - RNA interference (RNAi) is a naturally occurring regulatory process that controls
      posttranscriptional gene expression. Small interfering RNA (siRNA), a common form
      of RNAi-based therapeutics, offers new opportunities for cancer therapy via
      silencing specific genes, which are associated to cancer progress. However,
      clinical applications of RNAi-based therapy are still limited due to the easy
      degradation of siRNA during body circulation and the difficulty in the delivery
      of siRNA to desired tissues and cells. Thus, there have been many efforts to
      develop efficient siRNA delivery systems, which protect siRNA from serum
      nucleases and deliver siRNA to the intracellular region of target cells. Here,
      the recent advances in siRNA nanocarriers, which possess tumor-targeting ability
      are reviewed; various nanoparticle systems and their antitumor effects are
      summarized. The development of multifunctional nanocarriers for theranostics or
      combinatorial therapy is also discussed. 

PMID- 24577794
TI  - The calcium channel blocker verapamil inhibits oxidative stress response in
      Candida albicans.
AB  - Candida albicans is a common opportunistic fungal pathogen, causing both
      superficial candidiasis and life-threatening systemic infections in immune
      compromised individuals. Calcium signaling is responsible for this pathogen in
      responding to several stresses, such as antifungal drugs, alkaline pH and
      membrane-perturbing agents. Our recent study revealed that it is also involved in
      oxidative stress response. In this study, we investigated the effect of
      verapamil, an L-type voltage-gated calcium channel blocker, on oxidative stress
      response in this fungus. The addition of verapamil resulted in increased
      sensitivity to the oxidative agent H2O2, which is associated with a decrease of
      calcium fluctuation under the stress. Moreover, this agent caused enhanced
      oxidative stress, with increased levels of ROS and enhanced dysfunction of the
      mitochondria under the oxidative stress. Further investigations in SOD activity,
      GSH contents and expression of oxidative stress response-related genes indicated
      that the effect of verapamil is related to the repression of oxidative stress
      response. Our findings demonstrated that verapamil has an inhibitory effect on
      oxidative stress response, confirming the relationship between calcium signaling
      and oxidative stress in C. albicans. Therefore, calcium channels may be potential
      targets for therapy to enhance the efficacy of oxidative stress against C.
      albicans-related infections. 

PMID- 24577796
TI  - Subfascial involvement in glomuvenous malformation.
AB  - OBJECTIVE: Glomuvenous malformation (GVM) is an inherited autosomal dominant
      trait. The lesions, which appear as bluish nodules or plaque-like cutaneous
      elevations, are usually tender and more firm than sporadic venous malformations.
      Conventionally, the lesions are thought to be limited to the cutaneous and
      subcutaneous tissue planes. The objective was to characterize the depth of
      involvement of GVM lesions. MATERIALS AND METHODS: Magnetic resonance imaging
      (MRI) findings in GVM were retrospectively evaluated by two radiologists. The
      signal characteristics, tissue distribution, pattern of contrast enhancement of
      the lesions in GVM were documented. RESULTS: Thirty patients (19 female) aged 1
      35 years (mean 18 years) were diagnosed with GVM based on clinical features (n =
      20) and/or histopathological findings (n = 10). The lesions were present in the
      lower extremity (n = 15), upper extremity (n = 6), cervico-facial region (n = 6),
      pelvis (n = 2), and chest wall (n = 1). All patients had skin and subcutaneous
      lesions. Fifty percent of the patients (n = 15) demonstrated subfascial
      intramuscular (n = 15), intra-osseous (n = 1), and intra-articular involvement (n
      = 1). CONCLUSION: Contrary to the conventional belief that GVMs are generally
      limited to the skin and subcutaneous tissue, deep subfascial extension of the
      lesions is common.

PMID- 24577798
TI  - Erratum to: Clinical and pathological outcomes of renal cell carcinoma (RCC) in
      native kidneys of patients with end-stage renal disease: a long-term comparative
      retrospective study with RCC diagnosed in the general population.

PMID- 24577799
TI  - Does a history of depression actually mediate smoking-related pain? Findings from
      a cross-sectional general population-based study.
AB  - BACKGROUND: Smokers report more pain and worse functioning. The evidence from
      pain clinics suggests that depression affects this relationship: The association
      between smoking and chronic pain is weakened when controlling for depression.
      This study explored the relationship between smoking, pain and depression in a
      large general population-based cohort (Generation Scotland: Scottish Family
      Health Study). METHODS: Chronic pain measures (intensity, disability), self
      reported smoking status and a history of major depressive disorder (MDD) were
      analysed. A multivariate analysis of covariance determined whether smoking status
      was associated with both pain measures and a history of depressive illness. Using
      a statistical mediation model any mediating effect of depression on the
      relationship between smoking and chronic pain was sought. RESULTS: Of all 24,024
      participants, 30% (n = 7162) reported any chronic pain. Within this chronic pain
      group, 16% (n = 1158) had a history of MDD; 7108 had valid smoking data: 20% (n =
      1408) were current smokers, 33% (n = 2351) former and 47% (n = 3349) never
      smokers. Current smokers demonstrated higher pain intensity and pain-related
      disability scores compared with former and non-smokers (p < 0.001 for all
      analyses). From the mediation model, the effect on pain intensity decreased (p <
      0.001), indicating that the relationship between smoking and a history of
      depression contributes significantly to the effect of smoking on pain intensity.
      When applied to smoking-related pain disability, there was no mediation effect.
      CONCLUSIONS: In contrast to smokers treated in pain clinics, a history of MDD
      mediated the relationship between smoking and pain intensity, but not pain
      related disability in smokers in the community.

PMID- 24577801
TI  - Self-Assembled alpha-Fe2O3 mesocrystals/graphene nanohybrid for enhanced
      electrochemical capacitors.
AB  - Self-assembled alpha-Fe2O3 mesocrystals/graphene nanohybrids have been
      successfully synthesized and have a unique mesocrystal porous structure, a large
      specific surface area, and high conductivity. Mesocrystal structures have
      recently attracted unparalleled attention owing to their promising application in
      energy storage as electrochemical capacitors. However, mesocrystal/graphene
      nanohybrids and their growth mechanism have not been clearly investigated. Here
      we show a facile fabrication of short rod-like alpha-Fe2O3 mesocrystals/graphene
      nanohybrids by self-assembly of FeOOH nanorods as the primary building blocks on
      graphene under hydrothermal conditions, accompanied and promoted by concomitant
      phase transition from FeOOH to alpha-Fe2O3. A systematic study of the formation
      mechanism is also presented. The galvanostatic charge/discharge curve shows a
      superior specific capacitance of the as-prepared alpha-Fe2O3
      mesocrystals/graphene nanohybrid (based on total mass of active materials), which
      is 306.9 F g(-1) at 3 A g(-1) in the aqueous electrolyte under voltage ranges of
      up to 1 V. The nanohybrid with unique sufficient porous structure and high
      electrical conductivity allows for effective ion and charge transport in the
      whole electrode. Even at a high discharge current density of 10 A g(-1), the
      enhanced ion and charge transport still yields a higher capacitance (98.2 F g(
      1)), exhibiting enhanced rate capability. The alpha-Fe2O3 mesocrystal/graphene
      nanohybrid electrode also demonstrates excellent cyclic performance, which is
      superior to previously reported graphene-based hematite electrode, suggesting it
      is highly stable as an electrochemical capacitor.

PMID- 24577800
TI  - Association between maternal serum perfluoroalkyl substances during pregnancy and
      maternal and cord thyroid hormones: Taiwan maternal and infant cohort study.
AB  - BACKGROUND: Perfluoroalkyl substances (PFASs) are synthetic compounds that are
      widely used in industry and are often detectable in humans. In pregnant rats and
      their pups, PFASs can interfere with thyroid hormone homeostasis. In humans,
      maternal thyroid hormones supply the fetus throughout pregnancy, and thyroid
      hormones play a critical role in fetal growth and neurodevelopment. OBJECTIVES:
      We investigated the association between maternal PFAS exposure and thyroid
      hormone status in pregnant women and neonates. METHODS: In a study of
      environmental exposure and health in Taiwan, we measured serum concentrations of
      nine PFASs and four thyroid hormones for 285 pregnant women in their third
      trimester, and also measured cord serum thyroid hormones for 116 neonates.
      Associations between maternal PFASs and maternal and cord thyroid hormones were
      examined in multiple linear regression models. RESULTS: Perfluorohexanesulfonic
      acid concentrations were positively associated with maternal thyroid-stimulating
      hormone (TSH) levels. Pregnant women with higher levels of perfluorononanoic acid
      (PFNA), perfluoroundecanoic acid (PFUnDA), and perfluorododecanoic acid (PFDoDA)
      had lower free thyroxine (T4) and total T4 levels. For example, we estimated that
      maternal free T4 levels decreased 0.019 ng/dL (95% CI: -0.028, -0.009) with each
      nanogram per milliliter increase in maternal PFNA. Finally, maternal PFNA,
      PFUnDA, and PFDoDA levels were associated with lower cord total triiodothyronine
      (T3) and total T4 levels, and maternal perfluorodecanoic acid (PFDeA) was
      associated with lower cord total T3. CONCLUSIONS: Our results suggest that
      exposure to some PFASs during pregnancy may interfere with thyroid hormone
      homeostasis in pregnant women and fetuses.

PMID- 24577802
TI  - Negative religious coping as a correlate of suicidal ideation in patients with
      advanced cancer.
AB  - OBJECTIVE: The purpose of this study is to examine the relationship between
      negative religious coping (NRC) and suicidal ideation in patients with advanced
      cancer, controlling for demographic and disease characteristics and risk and
      protective factors for suicidal ideation. METHODS: Adult patients with advanced
      cancer (life expectancy <=6 months) were recruited from seven medical centers in
      the northeastern and southwestern USA (n = 603). Trained raters verbally
      administered the examined measures to patients upon study entry. Multivariable
      logistic regression analyses regressed suicidal ideation on NRC controlling for
      significant demographic, disease, risk, and protective factors. RESULTS: Negative
      religious coping was associated with an increased risk for suicidal ideation (OR,
      2.65 [95% CI, 1.22, 5.74], p = 0.01) after controlling for demographic and
      disease characteristics, mental and physical health, self-efficacy, secular
      coping, social support, spiritual care received, global religiousness and
      spirituality, and positive religious coping. CONCLUSIONS: Negative religious
      coping is a robust correlate of suicidal ideation. Assessment of NRC in patients
      with advanced cancer may identify patients experiencing spiritual distress and
      those at risk for suicidal ideation. Confirmation of these results in future
      studies would suggest the need for interventions targeting the reduction of NRC
      to reduce suicidal ideation among advanced cancer patients.

PMID- 24577803
TI  - Comparative analysis of 5 lung cancer natural history and screening models that
      reproduce outcomes of the NLST and PLCO trials.
AB  - BACKGROUND: The National Lung Screening Trial (NLST) demonstrated that low-dose
      computed tomography screening is an effective way of reducing lung cancer (LC)
      mortality. However, optimal screening strategies have not been determined to date
      and it is uncertain whether lighter smokers than those examined in the NLST may
      also benefit from screening. To address these questions, it is necessary to first
      develop LC natural history models that can reproduce NLST outcomes and simulate
      screening programs at the population level. METHODS: Five independent LC
      screening models were developed using common inputs and calibration targets
      derived from the NLST and the Prostate, Lung, Colorectal and Ovarian Cancer
      Screening Trial (PLCO). Imputation of missing information regarding smoking,
      histology, and stage of disease for a small percentage of individuals and
      diagnosed LCs in both trials was performed. Models were calibrated to LC
      incidence, mortality, or both outcomes simultaneously. RESULTS: Initially, all
      models were calibrated to the NLST and validated against PLCO. Models were found
      to validate well against individuals in PLCO who would have been eligible for the
      NLST. However, all models required further calibration to PLCO to adequately
      capture LC outcomes in PLCO never-smokers and light smokers. Final versions of
      all models produced incidence and mortality outcomes in the presence and absence
      of screening that were consistent with both trials. CONCLUSIONS: The authors
      developed 5 distinct LC screening simulation models based on the evidence in the
      NLST and PLCO. The results of their analyses demonstrated that the NLST and PLCO
      have produced consistent results. The resulting models can be important tools to
      generate additional evidence to determine the effectiveness of lung cancer
      screening strategies using low-dose computed tomography.

PMID- 24577805
TI  - 99mTc-MIBI imaging in thyroid nodules: is it useful?

PMID- 24577804
TI  - Health-related quality of life of children and adolescents with CKD stages 4-5
      and their caregivers.
AB  - BACKGROUND: Renal replacement therapies may affect the quality of life of
      patients and their primary caregivers (PC). METHODS: This study describes the
      perception of health-related quality of life (HRQoL) of children/adolescents with
      CKD stages 4-5, as well as of their PC (n = 64), in comparison to healthy peers
      and their PC (n = 129), respectively, based on the Peds QLTM 4.0 and Short Form
      36 (SF-36) questionnaires and selected biomarkers. RESULTS: Patients reported a
      deleterious impact on physical capacity and on social and school activities. A
      negative influence on emotional aspects was reported by older patients, but not
      by their PC. Hemodialysis, followed by peritoneal dialysis, had a more negative
      impact on patients' physical functioning domain. PC HRQol proxy reports differed
      from those of their children, especially in older patients. PC of both groups
      presented similar SF-36 scores. An association was demonstrated between the
      magnitude of treatment target inadequacies, lower specific dominion scores in the
      patients/PC proxy reports and PC SF-36 general health scores. CONCLUSION: The
      HRQoL of patients with CKD stages 4-5 is negatively affected to different degrees
      depending on age and treatment modality. The results suggest an association
      between worsening HRQoL parameters and inadequate control of recognized
      therapeutic CKD treatment targets.

PMID- 24577806
TI  - Relationships of organizational social capital with the presence of "gossip and
      slander," "quarrels and conflicts," sick leave, and poor work ability in nursing
      homes.
AB  - PURPOSE: This study aimed to explore the associations of organizational social
      capital (OSC) with the presence of "gossip and slander," the presence of
      "conflicts and quarrels," sick leave prevalence, and prevalence of poor work
      ability in frontline working personnel of nursing homes. METHODS: A total of 239
      subjects (81 % participation), working in 11 different nursing homes, took part
      in a cross-sectional questionnaire study. Following end points were considered,
      they are as follows: prevalence of "gossip and slander," "conflicts and
      quarrels," sick leave, and poor work ability. Associations with OSC were explored
      at individual level (binomial log-linear regression analysis) and on group level
      (Kendall's tau correlation coefficients). RESULTS: Significant associations were
      found between OSC and "gossip and slander," sick leave, and poor work ability,
      both in the individual- and group-level analyses. The associations showed a
      higher significance level in the group-level analyses, with the strongest
      association found between mean OSC of the workplace and the prevalence of poor
      work ability at the workplace (tau = -0.722; p = 0.002). CONCLUSIONS: This study
      demonstrated significant associations of OSC with three end points that are
      relevant within the framework of well-being at work in nursing homes. The results
      are suggestive that OSC should be treated as a characteristic of the entire
      workplace, rather than as an individually experienced characteristic. The
      strikingly strong association between OSC and prevalence of poor work ability is
      suggestive for an important role of OSC within the context of maintaining work
      ability.

PMID- 24577807
TI  - Does ultrasonography contribute significantly to the diagnosis of carpal tunnel
      syndrome?
AB  - BACKGROUND: Recent studies have demonstrated ultrasonography as a valuable tool
      for confirming the diagnosis of carpal tunnel syndrome. The objective of this
      study was to investigate sonographic parameters of the median nerve in patients
      diagnosed clinically with carpal tunnel syndrome. PATIENTS AND METHODS: 185
      wrists in 185 patients, 149 women (81%) and 36 men (19%), with a mean age of 59
      years, with the clinical diagnosis of carpal tunnel syndrome were examined
      sonographically. We measured cross-sectional area (CSA) of the median nerve at
      the forearm and at the carpal tunnel inlet, as well as the height (a-p dimension)
      of the nerve at the tunnel inlet and in the narrowest site in the carpal tunnel.
      Moreover, in all patients the severity of the disease was assessed by the Levine
      questionnaire. RESULTS: A significant variability of sonographic data
      characterizing the median nerve was found: the mean CSA at the tunnel inlet was
      17.6 mm2 (range: 7-36) and height of the nerve at the tunnel inlet was a mean of
      2.7 mm (range: 1.3-4.5). No correlation was found between sonographic data and
      severity of the syndrome as expressed by the Levine scores. CONCLUSION:
      Sonography of the median nerve contributes little to the diagnosis of a
      clinically relevant carpal tunnel syndrome and its routine use is not justified.

PMID- 24577808
TI  - World Health Organization-defined eosinophilic disorders: 2014 update on
      diagnosis, risk stratification, and management.
AB  - DISEASE OVERVIEW: The eosinophilias encompass a broad range of nonhematologic
      (secondary or reactive) and hematologic (primary, clonal) disorders with
      potential for end-organ damage. DIAGNOSIS: Hypereosinophilia (HE) has generally
      been defined as a peripheral blood eosinophil count greater than 1,500/mm(3) and
      may be associated with tissue damage. After exclusion of secondary causes of
      eosinophilia, diagnostic evaluation of primary eosinophilias relies on a
      combination of morphologic review of the blood and marrow, standard cytogenetics,
      fluorescent in situ hybridization, flow immunocytometry, and T-cell clonality
      assessment to detect histopathologic or clonal evidence for an acute or chronic
      myeloid or lymphoproliferative disorder. RISK STRATIFICATION: Disease prognosis
      relies on identifying the subtype of eosinophilia. After evaluation of secondary
      causes of eosinophilia, the 2008 World Health Organization establishes a
      semimolecular classification scheme of disease subtypes including "myeloid and
      lymphoid neoplasms with eosinophilia and abnormalities of PDGFRA, PDGFRB, or
      FGFR1', chronic eosinophilic leukemia, not otherwise specified" (CEL, NOS),
      lymphocyte-variant HE, and idiopathic hypereosinophilic syndrome (HES), which is
      a diagnosis of exclusion. RISK-ADAPTED THERAPY: The goal of therapy is to
      mitigate eosinophil-mediated organ damage. For patients with milder forms of
      eosinophilia (e.g., <1,500/mm(3)) without symptoms or signs of organ involvement,
      a watch and wait approach with close-follow-up may be undertaken. Identification
      of rearranged PDGFRA or PDGFRB is critical because of the exquisite
      responsiveness of these diseases to imatinib. Corticosteroids are first-line
      therapy for patients with lymphocyte-variant HE and HES. Hydroxyurea and
      interferon-alpha have demonstrated efficacy as initial treatment and steroid
      refractory cases of HES. In addition to hydroxyurea, second-line cytotoxic
      chemotherapy agents and hematopoietic cell transplant have been used for
      aggressive forms of HES and CEL with outcomes reported for limited number of
      patients. Although clinical trials have been performed with anti-IL-5
      (mepolizumab) and anti-CD52 (alemtuzumab) antibodies, their therapeutic role in
      primary eosinophilic diseases and HES has yet to be established.

PMID- 24577810
TI  - Understanding stability trends along the lanthanide series.
AB  - The stability trends across the lanthanide series of complexes with the
      polyaminocarboxylate ligands TETA(4-) (H4TETA=2,2',2'',2'''-(1,4,8,11
      tetraazacyclotetradecane-1,4,8,11-tetrayl)tetraacetic acid), BCAED(4-)
      (H4BCAED=2,2',2'',2'''-{[(1,4-diazepane-1,4-diyl)bis(ethane-2,1
      diyl)]bis(azanetriyl)}tetraacetic acid), and BP18C6(2-) (H2BP18C6=6,6'
      [(1,4,10,13-tetraoxa-7,16-diazacyclooctadecane-7,16
      diyl)bis(methylene)]dipicolinic acid) were investigated using DFT calculations.
      Geometry optimizations performed at the TPSSh/6-31G(d,p) level, and using a
      46+4f(n) ECP for lanthanides, provide bond lengths of the metal coordination
      environments in good agreement with the experimental values observed in the X-ray
      structures. The contractions of the Ln(3+) coordination spheres follow quadratic
      trends, as observed previously for different isostructural series of complexes.
      We show here that the parameters obtained from the quantitative analysis of these
      data can be used to rationalize the observed stability trends across the 4f
      period. The stability trends along the lanthanide series were also evaluated by
      calculating the free energy for the reaction [La(L)](n+/-)(sol)+Ln(3+)(sol)
      >[Ln(L)](n+/-)(sol)+La(3+)(sol). A parameterization of the Ln(3+) radii was
      performed by minimizing the differences between experimental and calculated
      standard hydration free energies. The calculated stability trends are in good
      agreement with the experimental stability constants, which increase markedly
      across the series for BCAED(4-) complexes, increase smoothly for the TETA(4-)
      analogues, and decrease in the case of BP18C6(2-) complexes. The resulting
      stability trend is the result of a subtle balance between the increased binding
      energies of the ligand across the lanthanide series, which contribute to an
      increasing complex stability, and the increase in the absolute values of
      hydration energies along the 4f period.

PMID- 24577809
TI  - Isolation of antifungal compound from Paeonia suffruticosa and its antifungal
      mechanism.
AB  - OBJECTIVE: To isolate antifungal compound from Paeonia suffruticosa, and to find
      the antifungal mechanisms by observing the ultrastructural modifications of
      yeasts in growth phase produced by 1,2,3,4,6-penta-O-galloyl-beta-D-glucose
      (PGG). METHODS: Peony (Paeonia suffruticosa) root bark (PRB) was separated by
      solvent extraction and purified by high performance liquid chromatography (HPLC)
      method using analytical and preparative reversed phase C18 column on the basis of
      bio-assay method. In order to investigate the antifungal mechanism of PGG, Yeasts
      were submitted to different concentrations [3 * minimum inhibition concentration
      (MIC), 0.3 * MIC] for 1 h under constant stirring at 30  degrees C, and
      transmission electron microscopy was performed. RESULTS: Based on the antifungal
      activity of PRB on Candida glabrata CBS138, the antifungal compound were isolated
      in ethyl acetate layer of PRB and identified as PGG by mass spectrometry, 1H
      nuclear magnetic resonance (NMR) analyses, with molecular weight of 940 and
      molecular formular as C41H32O26. Transmission electron microscopy showed that PGG
      degraded the cell wall envelope. CONCLUSION: The results suggest that PGG may be
      responsible for the antifungal activity of PRB by disrupting the structure of
      cell wall directly.

PMID- 24577811
TI  - Prognosis after resection of hepatitis B virus-related hepatocellular carcinoma
      originating from non-cirrhotic liver.
AB  - BACKGROUND: Long-term prognosis after resection of hepatitis B virus (HBV)
      related hepatocellular carcinoma (HCC) originating from non-cirrhotic liver is
      not fully clarified. METHODS: A total of 183 patients who underwent curative
      hepatectomy for HCC without cirrhosis were classified into two groups: HBV
      infection group (n = 124) and non-HBV infection group (n = 59). Long-term
      postoperative outcomes were compared between the two groups. RESULTS: The 5-year
      postoperative overall survival (OS) and disease-free survival (DFS) were 42.6 and
      39.0 %, respectively, in the HBV infection group versus 52.3 and 46.5 % in the
      non-HBV infection group (both p > 0.05). When patients were subdivided according
      to TNM stages, OS in stages II or III HCC patients was similar between the two
      groups. In contrast, OS and DFS were significantly worse in stage I patients with
      HBV infection than those in stage I patients without HBV infection (p = 0.041 and
      0.038, respectively). Preoperative serum HBV DNA >4 log10 copies/mL and vascular
      invasion were independent factors associated with poor prognosis (p = 0.034 and
      0.017, respectively) for patients with HBV infection. CONCLUSIONS: After hepatic
      resection for HCC in non-cirrhotic liver, patients with HBV infection with early
      stage tumors had worse prognosis than patients without HBV infection, possibly
      due to the carcinogenetic potential of viral hepatitis in the remnant liver.
      Antiviral therapy should be considered after hepatectomy in patients with high
      HBV DNA levels.

PMID- 24577812
TI  - Correlation between fluid-fluid levels on initial MRI and the response to
      chemotherapy in stage IIb osteosarcoma.
AB  - BACKGROUND: The presence of fluid-fluid levels (FFLs) on osteosarcoma magnetic
      resonance imaging (MRI) is underestimated as a nonspecific finding; however, we
      hypothesized that FFL in conventional osteosarcoma may be indicative of
      chemoresistance. METHODS: In 567 stage IIB osteosarcoma patients, we evaluated
      the following: the incidence of FFL and their correlation with other
      clinicopathological variables; tumor volume change after chemotherapy and
      survival according to the presence of FFL; and the relationship between survival
      and the extent of FFL. RESULTS: One hundred eight (19 %) tumors showed FFL on
      initial MRI. FFL were correlated with proximal humeral location (P = 0.017),
      osteolytic on plain radiographs (P < 0.001), tumor enlargement after chemotherapy
      (P < 0.001), and poor histological response (P = 0.005). Large tumor (P < 0.01),
      proximal tumor location (P = 0.01), and presence of FFL (P < 0.01) were
      independent predictors of poor survival. Compared to the extensive FFL (more than
      one third of the tumor), small foci of FFL (less than one third of the tumor)
      showed a high tendency for tumor enlargement after chemotherapy (P < 0.001), poor
      histologic response (P = 0.001), and worse survival (P < 0.001). CONCLUSIONS: FFL
      on initial MRI could predict tumor progression after chemotherapy. Notably,
      tumors with small foci of FFL (less than one third of the tumor) have a high
      propensity for poor outcome. Patients with this finding should be considered for
      risk-adapted therapy.

PMID- 24577813
TI  - Cost implications of the SSO-ASTRO consensus guideline on margins for breast
      conserving surgery with whole breast irradiation in stage I and II invasive
      breast cancer.

PMID- 24577814
TI  - Radiation alone for solid tumors and the questionable development of therapy
      related myelodysplastic syndromes.

PMID- 24577815
TI  - Risk for developing myelodysplastic syndromes in prostate cancer patients
      definitively treated with radiation.
AB  - BACKGROUND: Exposure to ionizing radiation has been linked to myelodysplastic
      syndromes (MDS); it is not clear whether therapeutic radiation doses used for
      prostate cancer pose an increased MDS risk. METHODS: We performed a retrospective
      cohort study of prostate cancer patients diagnosed between 1986 and 2011 at
      Cleveland Clinic, comparing those who underwent definitive treatment with radical
      prostatectomy (RP) to radiotherapy either external beam radiotherapy (EBRT) or
      prostate interstitial brachytherapy (PI) and to population-based registries.
      Competing risk regression analyses were used to determine the cumulative risk of
      developing MDS. All statistical tests were two-sided. RESULTS: Of 10924 patients,
      5119 (47%) received radiation (n = 2183 [43%] in EBRT group and n = 2936 [57%] in
      PI group) and 5805 (53%) were treated with RP. Overall, 31 cases of MDS were
      observed, with age-adjusted incidence rates no higher than in population-based
      registries. In univariate analyses, advancing age (hazard ratio [HR] = 1.14; 95%
      confidence interval [CI] = 1.09 to 1.20; P < .001) and radiotherapy exposure (HR
      = 3.44; 95% CI = 1.41 to 8.37; P = .007) were statistically significantly
      associated with development of MDS. In multivariable analyses, although advanced
      age (HR = 1.13; 95% CI = 1.06 to 1.19; P < .001) remained statistically
      associated with MDS, radiation did not, although a small non-statistically
      significant trend existed for PI-treated patients. MDS rates were no higher than
      in population-based registries. CONCLUSIONS: With relatively short follow-up,
      prostate cancer patients definitively treated with radiation did not appear to
      have a statistically increased risk of subsequent MDS.

PMID- 24577817
TI  - Were you identified to be at high fracture risk by FRAX(r) before your
      osteoporotic fracture occurred?
AB  - With the increasing longevity and the growing size of the aging population, China
      is among the developing countries with the greatest burden of osteoporotic
      fractures (OFs). Identification of individuals at high fracture risk to provide
      early treatment in developing countries with limited resources remains a
      challenge. Our aim was to calculate the FRAX(r) values in a selected mainland
      Chinese population the day before the occurrence of an OF and to compare the
      results with the Osteoporosis Foundation (NOF) thresholds. To define a population
      at high fracture risk, we selected patients in the orthopedic emergency cohort
      from Shanghai Sixth People's Hospital, China. To calculate the FRAX(r) the day
      before the actual OF, the actual fracture was not considered as a previous
      fracture. Subjects with a FRAX(r) value lower than the NOF thresholds were not
      considered at high risk. One-hundred ninety-eight patients were included with a
      mean age of 69.9 +/- 10.1 years old, and 78.8 % were female. Major fracture sites
      included hip (41.9 %), proximal humerus (22.2 %), forearm (27.8 %), spine (6.6
      %), and pelvis (1.5 %). Overall, only two (1.0 %) patients had a 10-year major
      fracture probability >=20 %, and 84 (42.4 %) patients had a 10-year hip fracture
      probability >=3 %. More than half of the population was not identified to be at
      high risk by the FRAX(r) BMI (body mass index). For age groups 55-59, 60-69, 70
      79, and 80-90 years old, respectively, the mean FRAX(r) BMI values (major OF/hip
      fracture) were 3.5/0.7, 5.7/1.8, 8.2/4.7, and 8.6/4.8 %. Dual-energy X-ray
      absorptiometry was available for 58 patients, and 41.2 % had a T-score <= -2.5
      standard deviation (lumbar spine and/or femoral neck and/or total hip). Only six
      (17.6 %) patients with a normal or osteopenic BMD were classified at high risk by
      the FRAX(r) BMD (bone mineral density). The NOF thresholds could only identify
      fewer than half of the studied population to be at high risk the day before an
      actual OF, and the 10-year hip fracture probability seemed to perform better than
      the 10-year major fracture probability. Prospective population-based studies are
      needed to validate the prediction of Chinese FRAX(r) model and to establish ideal
      thresholds. 

PMID- 24577816
TI  - Systemic lupus erythematosus: a therapeutic challenge for the XXI century.
AB  - Despite significant advances in our understanding of the pathogenesis of systemic
      lupus erythematosus (SLE), there are only a few drugs approved by the regulatory
      agencies across the world for the treatment of these patients; in fact, many of
      the compounds subjected to clinical trials have failed in achieving their primary
      endpoints. Current therapeutic options include antimalarials which should be used
      in all SLE patients unless they are strongly contraindicated, glucocorticoids
      which should be used at the lowest possible dose and for the shortest possible
      time, and immunosuppressive drugs which should be used judiciously, mainly in
      patients with severe organ involvements or receiving high doses of steroids to
      control their disease. Despite improvement on the survival of SLE patients,
      damage accrual has not varied over the last few decades, reflecting a gap between
      these therapeutic options and the expectations of these patients and their
      treating physicians. Biologic compounds can be used in some refractory cases.
      However, their cost is of great concern for both the patients and the health
      system. Cost is of special importance in low-income countries, because low-income
      SLE patients tend to experience a more severe disease having an overall worse
      prognosis which is compounded by their limited access to the health system.
      Although a treatment to target based on defined molecular pathways for specific
      disease subsets is appealing, this is not yet a reality. This review addressed
      current therapeutic options for SLE patients and the state of the art of
      investigational drugs targeting pathogenic pathways identified in these patients.

PMID- 24577818
TI  - The performance of a point of care test for detection of anti-mutated
      citrullinated vimentin and rheumatoid factor in early rheumatoid arthritis.
AB  - The purpose of this study was to determine the diagnostic performance of a point
      of-care test (POCT) for detection of anti-mutated citrullinated vimentin (anti
      MCV) and rheumatoid factor (RF) in early rheumatoid arthritis (RA) with 2 years
      of disease duration or less. Additionally, we evaluated the agreement of these
      tests when using EDTA whole blood and capillary blood. Patients with RA and other
      rheumatic disorders were consecutively recruited from the rheumatology outpatient
      clinic. The POCT for detection of anti-MCV and RF using capillary blood and EDTA
      whole blood was performed in 78 patients with early RA, 55 patients with other
      rheumatic disorders, and 55 healthy blood donors. The sensitivity and specificity
      of anti-MCV POCT in patients with early RA were 64 and 97 %, respectively, while
      the sensitivity and specificity of RF POCT were 51 and 95 %, respectively. The
      positive likelihood ratio of the POCT for anti-MCV was higher than those for RF
      (23.5 vs 9.4). The negative likelihood was 0.37 for anti-MCV and 0.52 for RF.
      There were three cases with false positive for anti-MCV including a patient with
      psoriatic arthritis and the other two with systemic sclerosis. The agreement
      between capillary blood and EDTA whole blood testing for anti-MCV and RF was low
      to moderate with Cohen's kappa of 0.58 and 0.49, respectively. This POCT for
      detection of anti-MCV and RF yielded high specificity and may be a valuable tool
      for the diagnosis of early RA. Using this POCT with EDTA whole blood instead of
      capillary blood is not recommended. 

PMID- 24577819
TI  - Ethical issues in pain and omics research. Some points to start the debate.

PMID- 24577820
TI  - Utilizing DNA analysis to combat the world wide plague of present day slavery-
      trafficking in persons.
AB  - A study was conducted to determine if modern forensic DNA typing methods can be
      properly employed throughout the world with a final goal of increasing arrests,
      prosecutions, and convictions of perpetrators of modern day trafficking in
      persons while concurrently reducing the burden of victim testimony in legal
      proceedings. Without interruption of investigations, collection of samples
      containing DNA was conducted in a variety of settings. Evidentiary samples were
      analyzed on the ANDE Rapid DNA system. Many of the collected swabs yielded
      informative short tandem repeat profiles with Rapid DNA technology. 

PMID- 24577822
TI  - Slovenian population data for five new European Standard Set short tandem repeat
      loci and SE33 locus.
AB  - AIM: To establish the allele distribution and statistical parameters of forensic
      interest for the D10S1248, D22S1045, D2S441, D1S1656, D12S391, and SE33 loci in
      Slovenian population and to compare allele frequencies with those from other
      populations. METHODS: We analyzed blood and buccal swab samples from 333
      unrelated, healthy Slovenian individuals. All samples were genotyped using the
      AmpFlSTR NGM Kit to obtain the allele frequency data for the loci D10S1248,
      D22S1045, D2S441, D1S1656, and D12S391. Samples from 113 individuals were also
      analyzed using the PowerPlex ESX 17 system to obtain the allele frequency data
      for the SE33 locus. Allele frequencies and statistical parameters of forensic
      interest were determined and frequency profiles compared between Slovenian and
      other European Caucasian populations using the Arlequin software, version
      3.5.1.3. RESULTS: The investigated short tandem repeat (STR) loci in Slovenian
      population had a great discriminating potential with a combined discrimination
      power of 0.99999998. The highest discrimination power and polymorphism
      information content were observed for the SE33 locus, followed by loci D1S1656,
      D12S391, D10S1248, D2S441, and D22S1045. When Slovenian allele frequency
      distribution was compared with other European populations, deviations were found
      only for Spanish and Italian population for D2S441 and D12S391. CONCLUSION:
      Slovenian population does not differ significantly from other European
      populations in terms of allele frequency distributions for the six analyzed STR
      loci. Based on forensic efficiency values, SE33 may be considered the most
      informative locus, which makes it especially useful in forensic investigations.

PMID- 24577821
TI  - Validation of 58 autosomal individual identification SNPs in three Chinese
      populations.
AB  - AIM: To genotype and evaluate a panel of single-nucleotide polymorphisms for
      individual identification (IISNPs) in three Chinese populations: Chinese Han,
      Uyghur, and Tibetan. METHODS: Two previously identified panels of IISNPs, 86
      unlinked IISNPs and SNPforID 52-plex markers, were pooled and analyzed. Four SNPs
      were included in both panels. In total, 132 SNPs were typed on Sequenom
      MassARRAY(r) platform in 330 individuals from Han Chinese, Uyghur, and Tibetan
      populations. Population genetic indices and forensic parameters were determined
      for all studied markers. RESULTS: No significant deviation from Hardy-Weinberg
      equilibrium was observed for any of the SNPs in 3 populations. Expected
      heterozygosity (He) ranged from 0.144 to 0.500 in Han Chinese, from 0.197 to
      0.500 in Uyghur, and from 0.018 to 0.500 in Tibetan population. Wright's Fst
      values ranged from 0.0001 to 0.1613. Pairwise linkage disequilibrium (LD)
      calculations for all 132 SNPs showed no significant LD across the populations
      (r(2)<0.147). A subset of 58 unlinked IISNPs (r(2)<0.094) with He>0.450 and Fst
      values from 0.0002 to 0.0536 gave match probabilities of 10-25 and a cumulative
      probability of exclusion of 0.999992. CONCLUSION: The 58 unlinked IISNPs with
      high heterozygosity have low allele frequency variation among 3 Chinese
      populations, which makes them excellent candidates for the development of
      multiplex assays for individual identification and paternity testing.

PMID- 24577823
TI  - Reliability of long vs short COI markers in identification of forensically
      important flies.
AB  - AIM: To compare the reliability of short and long cytochrome oxidase I gene
      fragment (COI) in identification of forensically important Diptera from Egypt and
      China. METHODS: We analyzed 50 specimens belonging to 18 species. The two
      investigated markers were amplified by polymerase chain reaction (PCR) followed
      by direct sequencing. Nucleotide sequence divergences were calculated using the
      Kimura two-parameter (K2P) distance model and neighbor-joining (NJ) phylogenetic
      trees. RESULTS: Although both tested fragments showed an overlap between intra
      and interspecific variations, long marker had greater completeness of
      monophyletic separation with high bootstrap support. Moreover, NJ tree based on
      the long fragment clustered species more in accordance with their taxonomic
      classification than that based on the short fragment. CONCLUSION: In dipterous
      identification, it is recommended to use the long COI marker due to its greater
      reliability and safety.

PMID- 24577824
TI  - Eicosapentaenoic acid in serum lipids could be inversely correlated with severity
      of clinical symptomatology in Croatian war veterans with posttraumatic stress
      disorder.
AB  - AIM: To explore the association between plasma fatty acids composition and the
      severity of clinical symptoms in Croatian war veterans with posttraumatic stress
      disorder (PTSD). METHODS: This cross-sectional study included 62 men diagnosed
      with PTSD caused by combat activities during the War in Croatia 1991-1995.
      Clinician-Administered PTSD Scale (CAPS), Hamilton Anxiety Rating Scale (HAM-A),
      and Hamilton Depression Rating Scale (HAM-D-17) were used. Plasma fatty acids
      composition was determined by gas chromatography. Data about life-style habits
      were collected by a structured interview. To evaluate the association between
      plasma fatty acid levels and PTSD severity scales, multivariate general linear
      models (GLM) were applied while controlling for different confounders. RESULTS:
      Significant negative correlations were found between plasma eicosapentaenoic acid
      (EPA, 20:5n-3) level and the scores on psychological scales (tau = -0.326,
      P<0.001 for CAPS; tau-0.304, P =0 .001 for HAM-A; and tau = -0.345, P<0.001 for
      HAM-D-17). GLM confirmed that PTSD severity was affected by EPA (Wilks'Lambda =
      0.763-0.805, P = 0.006-0.018, etap 0.195-0.237), arachidonic acid (AA)/EPA
      (Wilks'Lambda = 0.699-0.757, P = 0.004, etap 0.243-0.301), and dairy products
      consumption (Wilks'Lambda = 0.760-0.791, P = 0.045-0.088, etap 0.128-0.111). No
      other fatty acid or dietary/lifestyle variable was significant ( P = 0.362
      0.633). CONCLUSION: The study suggests that lower EPA levels are associated with
      the severity of clinical symptoms in PTSD.

PMID- 24577825
TI  - Estrogen receptor 1 gene (TA)n polymorphism is associated with lone atrial
      fibrillation in men.
AB  - AIM: To determine the association between the number of thymine-adenine (TA)n
      dinucleotide repeats in the promoter region of the gene coding for the estrogen
      receptor alpha (ESR1) and the prevalence of lone atrial fibrillation (AF) in men.
      METHODS: We conducted a case-control study involving 89 men with lone AF and 166
      healthy male controls. The ESR1 genotype was established by polymerase chain
      reaction and capillary electrophoresis. To assess the association of ESR1
      genotype with AF, logistic regression models were built with AF as outcome.
      RESULTS: Men with lone AF had significantly greater number of (TA)n repeats of
      single alleles than controls (mean +/- standard deviation, 19.2 +/- 4.2 vs 18 +/-
      4.3, P = 0.010). After adjustment for other factors, a unit-increase in (TA)n
      repeat number was associated with a significantly greater likelihood of AF (odds
      ratio 1.069; 95% confidence interval 1.024-1.116, P=0.002). CONCLUSIONS: Our
      results indicate that a greater number of (TA)n repeats in the promoter region of
      ESR1 is associated with a significantly increased likelihood of lone atrial
      fibrillation in men.

PMID- 24577826
TI  - Increased survival after irradiation followed by regeneration of bone marrow
      stromal cells with a novel thiol-based radioprotector.
AB  - AIM: To investigate the survival of laboratory rats after irradiation and to
      study the cellularity of their bone marrow and the multipotential mesenchymal
      stem cells (BM-MSCs) in groups treated with or without a new thiol-based
      radioprotector (GM2011). METHODS: Animals were irradiated by a Cobalt gamma
      source at 6.7 Gy. Treated animals were given i.p. GM2011 30 minutes before and 3
      and 7 hours after irradiation. Controls consisted of sham irradiated animals
      without treatment and animals treated without irradiation. After 30 days post
      irradiation, animals were sacrificed and bone marrow cells were prepared from
      isolated femurs. A colony forming unit-fibroblast (CFU-F) assay was performed to
      obtain the number of BM-MSCs. RESULTS: In the treated group, 87% of animals
      survived, compared to only 30% in the non-treated irradiated group. Irradiation
      induced significant changes in the bone marrow of the treated rats (total bone
      marrow cellularity was reduced by~60%--from 63 to 28 cells * 10(6)/femur and the
      frequency of the CFU-F per femur by~70% - from 357 to 97), however GL2011 almost
      completely prevented the suppressive effect observed on day 30 post-irradiation
      (71 cells * 10(6)/femur and 230 CFU-F/femur). CONCLUSION: Although the
      irradiation dosage was relatively high, GL2011 acted as a very effective new
      radioprotector. The recovery of the BN-MSCs and their counts support the
      effectiveness of the studied radioprotector.

PMID- 24577827
TI  - Mondino de Luzzi: a luminous figure in the darkness of the Middle Ages.

PMID- 24577828
TI  - Distortion, confusion, and impasses: could a public dialogue within Knowledge
      Landscapes contribute to better communication and understanding of innovative
      knowledge?

PMID- 24577830
TI  - Where art meets neuroscience: a new horizon of art therapy.

PMID- 24577829
TI  - Self-correction in biomedical publications and the scientific impact.
AB  - AIM: To analyze mistakes and misconduct in multidisciplinary and specialized
      biomedical journals. METHODS: We conducted searches through PubMed to retrieve
      errata, duplicate, and retracted publications (as of January 30, 2014). To
      analyze publication activity and citation profiles of countries,
      multidisciplinary, and specialized biomedical journals, we referred to the latest
      data from the SCImago Journal and Country Rank database. Total number of indexed
      articles and values of the h-index of the fifty most productive countries and
      multidisciplinary journals were recorded and linked to the number of duplicate
      and retracted publications in PubMed. RESULTS: Our analysis found 2597 correction
      items. A striking increase in the number of corrections appeared in 2013, which
      is mainly due to 871 (85.3%) corrections from PLOS One. The number of duplicate
      publications was 1086. Articles frequently published in duplicate were reviews
      (15.6%), original studies (12.6%), and case reports (7.6%), whereas top three
      retracted articles were original studies (10.1%), randomized trials (8.8%), and
      reviews (7%). A strong association existed between the total number of
      publications across countries and duplicate (rs=0.86, P<0.0001) and retracted
      items (rs=0.812, P<0.0001). A similar trend was found between country-based h
      index values and duplicate and retracted publications. CONCLUSION: The study
      suggests that the intensified self-correction in biomedicine is due to the
      attention of readers and authors, who spot errors in their hub of evidence-based
      information. Digitization and open access confound the staggering increase in
      correction notices and retractions.

PMID- 24577831
TI  - Propranolol efficiency in prevention of sustained ventricular tachycardia in
      patients with implanted cardioverter-defibrillator: a case series.

PMID- 24577832
TI  - Antimongoloid as a pejorative term.

PMID- 24577833
TI  - Person-centered health education and training.

PMID- 24577834
TI  - Zagreb declaration on person centered health professional education.

PMID- 24577835
TI  - Congress statement on the appraisal and prospects for person-centered medicine in
      croatia.

PMID- 24577836
TI  - Reply: To PMID 24574210.

PMID- 24577837
TI  - Decreased insulin-like growth factor-I and its receptor expression in the
      hippocampus and somatosensory cortex of the aged mouse.
AB  - Insulin-like growth factor-I (IGF-I) is a multifunctional polypeptide and has
      diverse effects on brain functions. In the present study, we compared IGF-I and
      IGF-I receptor (IGF-IR) immunoreactivity and their protein levels between the
      adult (postnatal month 6) and aged (postnatal month 24) mouse hippocampus and
      somatosensory cortex. In the adult hippocampus, IGF-I immunoreactivity was easily
      observed in the pyramidal cells of the stratum pyramidale in the hippocampus
      proper and in the granule cells of the granule cell layer of the dentate gyrus.
      In the adult somatosensory cortex, IGF-I immunoreactivity was easily found in the
      pyramidal cells of layer V. In the aged groups, IGF-I expression was dramatically
      decreased in the cells. Like the change of IGF-I immunoreactivity, IGF-IR
      immunoreactivity in the pyramidal and granule cells of the hippocampus and in the
      pyramidal cells of the somatosensory cortex was also markedly decreased in the
      aged group. In addition, both IGF-I and IGF-IR protein levels were significantly
      decreased in the aged hippocampus and somatosensory cortex. These results
      indicate that the apparent decrease of IGF-I and IGF-IR expression in the aged
      mouse hippocampus and somatosensory cortex may be related to age-related changes
      in the aged brain. 

PMID- 24577838
TI  - Disparity in perceptions of disease characteristics, treatment effectiveness, and
      factors influencing treatment adherence between physicians and patients with
      myelodysplastic syndromes.
AB  - BACKGROUND: Previous studies have suggested that many patients with
      myelodysplastic syndromes (MDS) have an incomplete understanding of their
      disease, which may influence adherence to prescribed regimens and outcomes.
      METHODS: To better understand physician and patient perceptions about MDS and MDS
      therapy, the authors conducted 2 surveys in February 2012: 1 for patients with
      MDS and 1 for health care professionals (HCPs) who cared for patients with MDS.
      Patient and HCP surveys consisted of 57 and 49 questions, respectively, assessing
      understanding of MDS, perceptions of specific treatments, barriers to treatment
      adherence, and treatment experience. RESULTS: In total, 477 complete patient
      responses and 120 complete HCP responses were received. Among patient responders,
      63% were aged >=60 years, and 42% had received at least 1 disease-modifying
      therapy. Of the 61 physician responders, 57% practiced in an academic setting,
      and 43% practiced in the community; 71% of the 59 nonphysician HCPs worked in the
      community setting. Only 10% of patients agreed that MDS represented "cancer"
      compared with 59% of physicians and 46% of nonphysician HCPs (P < .001). Only 29%
      of patients reported that MDS was ever "curable" compared with 52% of physicians
      (P < .001). Physicians viewed the potential benefits of active therapy as greater
      than patients, but patients perceived the actual treatment experience more
      positively than physicians and differed from physicians in perceived reasons for
      stopping therapy. CONCLUSIONS: Physicians, nonphysician HCPs, and patients with
      MDS have disparate views of MDS characteristics and the value and limitations of
      treatments for MDS. Improved communication and education may increase
      understanding and achieve better treatment adherence and patient outcomes.

PMID- 24577840
TI  - Persistence of the mitochondrial lineage responsible for the Irish potato famine
      in extant new world phytophthora infestans.
AB  - The plant pathogen Phytophthora infestans emerged in Europe in 1845, triggering
      the Irish potato famine and massive European potato crop losses that continued
      until effective fungicides were widely employed in the 20th century. Today the
      pathogen is ubiquitous, with more aggressive and virulent strains surfacing in
      recent decades. Recently, complete P. infestans mitogenome sequences from 19th
      century herbarium specimens were shown to belong to a unique lineage (HERB-1)
      predicted to be rare or extinct in modern times. We report 44 additional P.
      infestans mitogenomes: four from 19th-century Europe, three from 1950s UK, and 37
      from modern populations across the New World. We use phylogenetic analyses to
      identify the HERB-1 lineage in modern populations from both Mexico and South
      America, and to demonstrate distinct mitochondrial haplotypes were present in
      19th-century Europe, with this lineage initially diversifying 75 years before the
      first reports of potato late blight. 

PMID- 24577839
TI  - Predictors of plasma DDT and DDE concentrations among women exposed to indoor
      residual spraying for malaria control in the South African Study of Women and
      Babies (SOWB).
AB  - BACKGROUND: Few studies have examined predictors of DDT
      (dichlorodiphenyltrichloroethane) and DDE (dichlorodiphenyldichloroethylene)
      levels among residents in homes sprayed with DDT for malaria control with the aim
      of identifying exposure-reduction strategies. METHODS: The present analysis
      included 381 women enrolled in the Study of Women and Babies (SOWB) during 2010
      2011, from eight South African villages in the Limpopo Province, South Africa.
      Indoor residual spraying (IRS) occurred in half of the villages. Questionnaires
      regarding various demographic and medical factors were administered and blood
      samples were obtained. We classified the women into three exposure groups by type
      of residence: unsprayed village (n = 175), IRS village in household with a low
      likelihood of DDT use (non-DDT IRS household, n = 106), IRS village in household
      with a high likelihood of DDT use (DDT IRS household, n = 100). We used
      multivariable models of natural log-transformed DDT plasma levels (in micrograms
      per liter) and DDE (in micrograms per liter) to identify predictors for each
      group. RESULTS: Median levels of DDT and DDE among women in unsprayed villages
      were 0.3 [interquartile range (IQR): 0.1-0.9] and 1.7 (IQR: 0.7-5.5),
      respectively. Median levels of DDT and DDE among women in DDT IRS households were
      2.6 (IQR: 1.1-6.6) and 8.5 (IQR: 4.7-18.0), respectively. In unsprayed villages,
      women with water piped to the yard, rather than a public tap, had 73% lower DDT
      (95% CI: -83, -57%) and 61% lower DDE (95% CI: -74, -40%) levels. In DDT IRS
      households, women who reported taking more than six actions to prepare their home
      before IRS (e.g., covering water and food) had 40% lower DDT levels (95% CI: -63,
      -0.3%) than women who took fewer than four actions. CONCLUSION: The predictors of
      DDT and DDE plasma levels identified in the present study may inform
      interventions aimed at decreasing exposure. Among households where DDT is likely
      to be used for IRS, education regarding home preparations may provide an
      interventional target.

PMID- 24577841
TI  - Evolutionary interrogation of human biology in well-annotated genomic framework
      of rhesus macaque.
AB  - With genome sequence and composition highly analogous to human, rhesus macaque
      represents a unique reference for evolutionary studies of human biology. Here, we
      developed a comprehensive genomic framework of rhesus macaque, the RhesusBase2,
      for evolutionary interrogation of human genes and the associated regulations. A
      total of 1,667 next-generation sequencing (NGS) data sets were processed,
      integrated, and evaluated, generating 51.2 million new functional annotation
      records. With extensive NGS annotations, RhesusBase2 refined the fine-scale
      structures in 30% of the macaque Ensembl transcripts, reporting an accurate, up
      to-date set of macaque gene models. On the basis of these annotations and
      accurate macaque gene models, we further developed an NGS-oriented Molecular
      Evolution Gateway to access and visualize macaque annotations in reference to
      human orthologous genes and associated regulations (www.rhesusbase.org/molEvo).
      We highlighted the application of this well-annotated genomic framework in
      generating hypothetical link of human-biased regulations to human-specific
      traits, by using mechanistic characterization of the DIEXF gene as an example
      that provides novel clues to the understanding of digestive system reduction in
      human evolution. On a global scale, we also identified a catalog of 9,295 human
      biased regulatory events, which may represent novel elements that have a
      substantial impact on shaping human transcriptome and possibly underpin recent
      human phenotypic evolution. Taken together, we provide an NGS data-driven,
      information-rich framework that will broadly benefit genomics research in general
      and serves as an important resource for in-depth evolutionary studies of human
      biology. 

PMID- 24577843
TI  - Antiphopholipid antibodies and functional activated protein C resistance in
      patients with breast cancer during anthracycline-based chemotherapy administered
      through an intravenous port-catheter device.

PMID- 24577842
TI  - Genome-wide disruption of gene expression in allopolyploids but not hybrids of
      rice subspecies.
AB  - Hybridization and polyploidization are prominent processes in plant evolution.
      Hybrids and allopolyploids typically exhibit radically altered gene expression
      patterns relative to their parents, a phenomenon termed "transcriptomic shock."
      To distinguish the effects of hybridization from polyploidization on coregulation
      of divergent alleles, we analyzed expression of parental copies (homoeologs) of
      11,608 genes using RNA-seq-based transcriptome profiling in reciprocal hybrids
      and tetraploids constructed from subspecies japonica and indica of Asian rice
      (Oryza sativa L.). The diploid hybrids and their derived allopolyploids differ
      dramatically in morphology, despite having the same suite of genes and genic
      proportions. Allelic and homoeolog-specific transcripts were unequivocally
      diagnosed in the hybrids and tetraploids based on parent-specific SNPs. Compared
      with the in silico hybrid (parental mix), the range of progenitor expression
      divergence was significantly reduced in both reciprocally generated F1 hybrids,
      presumably due to the ameliorating effects of a common trans environment on
      divergent cis-factors. In contrast, parental expression differences were greatly
      elaborated at the polyploid level, which we propose is a consequence of
      stoichiometric disruptions associated with the numerous chromosomal packaging and
      volumetric changes accompanying nascent polyploidy. We speculate that the
      emergent property of "whole genome doubling" has repercussions that reverberate
      throughout the transcriptome and downstream, ultimately generating altered
      phenotypes. This perspective may yield insight into the nature of adaptation and
      the origin of evolutionary novelty accompanying polyploidy. 

PMID- 24577845
TI  - The detection and measurement of interleukin-6 in venous and capillary blood
      samples, and in sweat collected at rest and during exercise.
AB  - PURPOSE: This study aimed to quantify the relationship between venous and
      capillary blood sampling methods for the measurement of plasma interleukin-6 (IL
      6). A parallel study was conducted to determine the possibility of measuring IL-6
      in sweat using an enzyme-linked immunosorbent assay (ELISA) and investigate the
      relationship between plasma- and sweat-derived measures of IL-6. METHODS: Twelve
      male participants were recruited for the measurement of IL-6 at rest and during
      exercise (study 1). An additional group of five female participants was recruited
      for the measurement of IL-6 in venous blood versus sweat at rest and following
      exercise (study 2). In study 1, venous and capillary blood samples were collected
      at rest and in response to exercise. In study 2, venous and sweat samples were
      collected following exercise. RESULTS: Mean plasma IL-6 concentration was not
      different between venous and capillary blood sampling methods either at rest
      (4.27 +/- 5.40 vs. 4.14 +/- 4.45 pg ml(-1)), during (5.40 +/- 5.17 vs. 5.58 +/-
      6.34 pg ml(-1)), or in response to exercise (6.95 +/- 6.37 vs. 6.99 +/- 6.74 pg
      ml(-1)). There was no IL-6 detectable in sweat either at rest or following
      exercise. CONCLUSION: There are no differences in the measurement of plasma IL-6
      using either venous or capillary blood sampling methods. Capillary measurement
      represents a minimally invasive way of measuring IL-6 and detecting changes in IL
      6, which are linked to fatigue and overtraining.

PMID- 24577847
TI  - Lay providers can deliver effective cognitive behavior therapy for older adults
      with generalized anxiety disorder: a randomized trial.
AB  - BACKGROUND: The Institute of Medicine recommends developing a broader workforce
      of mental health providers, including nontraditional providers, to expand
      services for older adults. Cognitive behavior therapy (CBT) is effective for late
      life generalized anxiety disorder (GAD), but no study has examined outcomes with
      delivery by lay providers working under the supervision of licensed providers.
      The current study examined the effects of CBT delivered by lay, bachelor-level
      providers (BLP) relative to Ph.D.-level expert providers (PLP), and usual care
      (UC) in older adults with GAD. METHODS: Participants were 223 older adults (mean
      age, 66.9 years) with GAD recruited from primary care clinics at two sites and
      assigned randomly to BLP (n = 76), PLP (n = 74), or UC (n = 73). Assessments
      occurred at baseline and 6 months. CBT in BLP and PLP included core and elective
      modules (3 months: skills training; 3 months: skills review) delivered in person
      and by telephone, according to patient choice. RESULTS: CBT in both BLP and PLP
      groups significantly improved GAD severity (GAD Severity Scale), anxiety
      (Spielberger State-Trait Anxiety Inventory; Structured Interview Guide for the
      Hamilton Anxiety Scale), depression (Patient Health Questionnaire), insomnia
      (Insomnia Severity Index), and mental health quality of life (Short-Form-12),
      relative to UC. Response rates defined by 20% reduction from pre- to
      posttreatment in at least three of four primary outcomes were higher for study
      completers in BLP and PLP relative to UC (BLP: 38.5%; PLP: 40.0%; UC: 19.1%).
      CONCLUSION: Lay providers, working under the supervision of licensed providers,
      can deliver effective CBT.

PMID- 24577848
TI  - [Visual field defects after epilepsy surgery: implications for driving license
      tenure].
AB  - BACKGROUND: Epilepsy surgery is an effective and established therapy in medically
      uncontrollable seizure disorders. In the course of such operations lesions of the
      visual pathway are often unavoidable. The resultant visual field defects can
      conflict with the legal requirements for a driving license. METHODS: In this
      single center trial Goldmann perimetric findings in 135 temporal lobe epilepsy
      surgery procedures were analyzed retrospectively. The data were reviewed with
      respect to current and former German legal requirements for a driving license.
      RESULTS: Of the surgical procedures 64 % resulted in visual field defects, 50% of
      the postoperative visual field findings did not comply with the legal
      requirements for a driving license and 56% did not comply with those for a heavy
      goods vehicle driving license. DISCUSSION: A considerable proportion of the
      epilepsy surgery procedures examined in this study resulted in visual field
      defects that did not comply with the German legal requirements for driving
      vehicles. In all cases defects in the center of the visual field proved pivotal.

PMID- 24577849
TI  - Psychological morbidity and health-related quality of life in patients with
      differing awareness of cancer diagnosis: a cross-sectional study.
AB  - OBJECTIVE: Concealment of cancer diagnosis from patients is not rare worldwide
      and physicians in mainland China are in fact discouraged from disclosing a cancer
      diagnosis to cancer patients. Preventing worsened psychological morbidity is at
      the core of the argument for nondisclosure. The purpose of this study was to
      quantify anxiety, depression, and distress among patients with various degrees of
      awareness of their cancer diagnosis. Quality of life was also measured. METHODS:
      Using a cross-sectional and blinded design, the Hospital Anxiety and Depression
      Scale questionnaire, the Distress Thermometer, and the SF-36 Health Survey were
      administered to 287 hospitalized patients with oral and maxillofacial tumors.
      Independently, the patients' awareness of disease was assessed with
      semistructured interviews. RESULTS: Hospital Anxiety and Depression Scale,
      Distress Thermometer, and SF-36 did not identify significant differences in
      scores among the hospitalized patients with various degrees of awareness of their
      cancer diagnosis: an awaiting diagnosis group, a concealed diagnosis group, and a
      disclosed diagnosis group. CONCLUSIONS: Before surgery, inpatients who were
      hospitalized because of oral and maxillofacial tumors with various degrees of
      awareness of their cancer diagnosis had similar psychological morbidity and
      quality of life. Informing hospitalized cancer patients of their diagnosis before
      surgery may not deteriorate their psychiatric condition or their quality of life.

PMID- 24577851
TI  - Is histological examination always necessary to determine a cause of death? Of
      course it is!

PMID- 24577850
TI  - The role of histopathology in forensic practice: an overview.
AB  - The role of forensic histopathology in routine practice is to establish the cause
      of death in particular cases. This is achieved on the basis of microscopic
      analysis of representative cell and tissue samples taken from the major internal
      organs and from abnormal findings made at autopsy. A prerequisite of this is
      adherence to the quality standards set out for conventional
      histological/cytological staining and enzyme histochemical and
      immunohistochemical methods. The interpretation of histological findings is
      performed by taking into account macroscopic autopsy findings and information on
      previous history. Histological analysis may prompt postmortem biochemical and
      chemical-toxicological investigations. The results of histological analysis need
      to be classified by experts in the context of the available information and the
      need to withstand the scrutiny of other experts. 

PMID- 24577852
TI  - Heterotopic ossification following surgery: an unusual cause of resuscitation
      injury.

PMID- 24577854
TI  - Futsal and continuous exercise induce similar changes in specific skeletal muscle
      signalling proteins.
AB  - Exercise elicits skeletal-muscle adaptations which are important for improved
      health outcomes. We compared the effects of a futsal game (FUT) and moderate
      intensity continuous exercise (MOD), on the skeletal-muscle protein signalling
      responses in young, healthy individuals. 16 men undertook an incremental exercise
      test and a resting muscle biopsy performed >48 h apart. They were then randomly
      allocated to either FUT (n=12) consisting of 2 x 20 min halves, or MOD (n=8)
      consisting of a work-matched running bout performed at an intensity corresponding
      to the individual ventilatory threshold 1. Work matching was achieved by means of
      triaxial accelerometers. Immediately after FUT and MOD, participants underwent a
      second biopsy to assess exercise-induced changes in protein signalling. Total and
      phosphorylated protein abundance was assessed via western blotting. Both FUT and
      MOD altered signalling responses in skeletal muscle. FUT increased total ATF2
      protein abundance (p=0.048) and phosphorylation (p=0.029), while no changes
      occurred with MOD. Both exercise regimes increased ACC phosphorylation (p=0.01)
      and returned a trend for increased p38MAPK phosphorylation. Futsal may be
      employed as an alternative to continuous exercise to elicit muscle adaptations
      which may be associated with improved health outcomes. As only FUT increased ATF2
      activation, this protein might be a target of future investigation on exercise
      induced signalling. 

PMID- 24577853
TI  - Glucocorticoids predict 10-year fragility fracture risk in a population-based
      ambulatory cohort of men and women: Canadian Multicentre Osteoporosis Study
      (CaMos).
AB  - We determined the prospective 10-year association among incident fragility
      fractures and four glucocorticoid (GC) treatment groups (Never GC, Prior GC,
      Baseline GC, and Ever GC). Results showed that GC treatment is associated with
      increased 10-year incident fracture risk in ambulatory men and women across
      Canada. PURPOSE: Using the Canadian Multicentre Osteoporosis Study dataset, we
      determined the prospective 10-year association between incident fragility
      fractures and GC treatment. METHODS: We conducted a 10-year prospective
      observational cohort study at nine sites across Canada. A total of 9,263
      ambulatory men and women 25 years of age and older were included in the analysis.
      Multivariable Cox proportional hazards analyses were conducted to determine the
      relationship among GC treatment groups in four levels that included Never GC,
      Prior GC, Baseline GC, and Ever GC (combined baseline and prior groups) and time
      to fracture. RESULTS: In each of the Never GC, Prior GC, Baseline GC, and Ever GC
      treatment groups, the number of participants were 8,832 (95.4 %), 303 (3.3 %),
      128 (1.4 %), and 431 (4.7 %), respectively. Of the 9,263 individuals enrolled,
      incident fragility non-spine, hip, spine, and any fractures were experienced by a
      total of 896 (9.67 %), 157 (1.69 %), 130 (1.40 %), and 1,102 (11.90 %) over 10
      years, respectively. For men and women combined, prior GC treatment was
      associated with a higher hazard ratio (HR) for time to incident non-vertebral (HR
      = 1.5, 95 % confidence interval [CI] = 1.1, 2.0), hip (HR = 2.1, 95 % CI = 1.1,
      4.0), and any fracture (HR = 1.4, 95 % CI = 1.0, 1.8) compared with never GC
      treatment. CONCLUSIONS: GC treatment is associated with increased 10-year
      incident fracture risk; this highlights the importance of considering therapy to
      prevent GC-induced fractures for patients who are using GC for various medical
      conditions.

PMID- 24577855
TI  - Anatomical research on the subacromial interval following implantation of
      clavicle hook plates.
AB  - This article aimed to explore whether hook plate implantation significantly
      narrowed the subacromial space. 24 shoulder joints were implanted with clavicle
      hook plates. A Vernier caliper was used to measure the length and thickness of
      the acromion. In addition, the length and thickness of the hook of the plate were
      measured. The data from all measurements recorded were divided into 2 groups
      Group A, the length group: the length of acromion and the hook, and Group B, the
      thickness group: the thickness of acromion and the depth of hook. There are
      significant statistical differences when comparing between the subgroups within
      each group. The depth of the hook exceeds the thickness of the acromion (12.41+/
      2.80 mm vs. 10.44+/-2.59 mm, respectively), the hook plate implantation
      significantly narrowed the subacromial space by 1.97+/-1.19 mm (p<0.01), and the
      length of the hook was shorter than that of the acromion by 9.75+/-3.64 mm
      (p<0.01). Our findings revealed that the hook plate with only 3 depths could not
      match the acromion satisfactorily and the hook plate implantation significantly
      narrowed the subacromial space. A hook plate with a variable depth, which can
      match better with patient's anatomy, is worthy of further investigation in the
      future. 

PMID- 24577856
TI  - Lower extremity work is associated with club head velocity during the golf swing
      in experienced golfers.
AB  - While the golf swing is a complex whole body movement requiring coordination of
      all joints to achieve maximum ball velocity, the kinetic contribution of the
      lower extremities to club head velocity has not been quantified, despite the
      perception that the legs are a primary source of power during the swing.
      Mechanical power at the hips, knees, and ankles was estimated during the
      downswing phase of a full swing with a driver using a passive optical motion
      capture system and 2 force plates for adult males across a range of age and self
      reported skill levels. Total work by the lower extremities was calculated by
      integrating the powers of all 6 joints over the downswing. Regression analyses
      showed that total lower extremity work was a strong predictor of club head
      velocity (R=0.63). Secondary analyses showed different relationships to club head
      velocity in lead and trail leg lower extremity joints, but none of these were as
      predictive of club head velocity as the total work performed by the lower
      extremities. These results provide quantitative evidence that the lower body's
      kinetic contribution may be an important factor in achieving greater club head
      velocity, contributing to greater driving distance and overall golf performance. 

PMID- 24577857
TI  - Mechanical and physiological examination of barefoot and shod conditions in
      female runners.
AB  - Barefoot running and running using minimalist footwear have become increasingly
      popular in recent years. Footwear choice may affect running mechanics and the
      metabolic cost of running. To investigate these factors, 8 well-trained, female
      distance runners (mean age=20.1+/-1.4 years) were recruited to participate in the
      study. Following orientation to testing procedures, subjects completed 3 running
      economy tests on separate days. Treatment order (barefoot, minimalist footwear
      and running shoe) was counter-balanced. Each testing session consisted of a 5-min
      warm-up at 2.24 m . s(-1), followed by the 7-min RE test at 3.13 m . s(-1).
      Biomechanical data were collected at the 3-min mark for 10 s, and expired gases
      were collected from minutes 5-7. One-way repeated measures ANOVA revealed a
      statistically significant difference for running economy (p=0.04), expressed as
      relative oxygen uptake per km in the barefoot condition (running shoe: 204.51+/
      2.84; minimalist footwear: 198.21+/-3.04; barefoot: 193.26+/-3.62 ml . kg(-1).
      km(-1)) vs. running shoe. The other physiological and biomechanical variables
      were not statistically significant (p>0.05). However, moderate to large effect
      sizes suggested there were biomechanical changes that ensured between conditions.
      It should be further evaluated whether these mechanical adjustments and the
      running economy trend would translate into improved distance race performance
      while running barefoot or with minimalist footwear.

PMID- 24577858
TI  - Greater performance impairment of black runners than white runners when running
      in hypoxia.
AB  - This study aimed to compare the response of performance-matched black and white
      runners during maximal and sub-maximal running in normoxic and hypoxic
      conditions. 14 well-trained runners (8 black, 6 white) performed 2 incremental
      maximal exercise tests and 2 fatigue resistance tests at 21% O2 (normoxia) or 14%
      O2 (hypoxia). Respiratory parameters, heart rate (HR), lactate concentration
      ([La(-)]) as well as arterial saturation (SpO2) were measured. Enzyme activities
      and myosin heavy chain content (MHC) were also measured. White runners reached a
      significantly greater peak treadmill speed and a higher HRmax than black runners
      in hypoxia (p<0.05). Additionally, White runners achieved a greater time to
      fatigue than black runners (p<0.05), with black runners displaying a greater
      decline in performance in hypoxia compared to normoxia (20.3% vs. 13.4%, black
      vs. white, respectively). However, black runners presented lower [La(-)] and
      higher SpO2 than white runners in hypoxia (p<0.05). Black runners had a higher
      proportion of MHC IIa and higher lactate dehydrogenase activity (p<0.05). The
      greater performance impairment observed in black runners in hypoxia suggests a
      greater performance sensitivity to this condition, despite the maintenance of
      physiological variables such as SpO2 and [La (-) ] within a smaller range than
      white runners. 

PMID- 24577859
TI  - Slower nerve conduction velocity in individuals with functional ankle
      instability.
AB  - The purpose of this study is to quantify nerve conduction velocity differences in
      individuals with functional ankle instability compared to a "healthy" population.
      38 participants ages 18-30 were recruited from a large university with
      approximately 43,000 students. 19 subjects (9 men and 10 women; age=21.0+/-1.4
      years; height=172.0+/-9.3 cm; mass=74.4+/-1 2.4 kg) with symptoms of functional
      ankle instability were in the functional ankle instability group. 19 subjects (10
      men, 9 women; age=22.0+/-2.6 years; height=169.8+/-9.1 cm; mass=69.0+/-14.8 kg)
      with "healthy" ankles were in the control group. Nerve conduction velocity was
      conducted using one trial at 2 different sites: posterior to the fibular head
      (fibular), and 10 cm superior/posterior of the first site (popliteal). Nerve
      conduction velocity (m/sec) was assessed using a SierraWave II system (Cadwell
      Laboratories; Kennewick, WA). A MANCOVA was performed on the two dependent
      variables (fibular and popliteal). Covariates included surface temperature of the
      leg, body mass index, and age. The independent variable was group (functional
      ankle instability and control). The effect of group was significantly related to
      nerve conduction velocity at the fibular site (F(1, 27) =16.49, p=0.01) and
      popliteal site (F(1, 27)=4.51, p=0.01), with responses significantly faster for
      individuals in the control group than the functional ankle instability group.
      These results indicate that patients with functional ankle instability might have
      damage to the peroneal nerve which results in slower peroneal nerve conduction
      velocity.

PMID- 24577860
TI  - Exercise-induced dehydration does not alter time trial or neuromuscular
      performance.
AB  - This study examined the effect of exercise-induced dehydration by ~4% body mass
      loss on 5-km cycling time trial (TT) performance and neuromuscular drive,
      independent of hyperthermia. 7 active males were dehydrated on 2 occasions,
      separated by 7 d. Participants remained dehydrated (DEH, -3.8+/-0.5%) or were
      rehydrated (REH, 0.2+/-0.6%) over 2 h before completing the TT at 18-25  degrees
      C, 20-30% relative humidity. Neuromuscular function was determined before
      dehydration and immediately prior the TT. The TT started at the same core
      temperature (DEH, 37.3+/-0.3 degrees C; REH, 37.0+/-0.2  degrees C (P>0.05).
      Neither TT performance (DEH, 7.31+/-1.5 min; REH, 7.10+/-1.3 min (P>0.05)) or %
      voluntary activation were affected by dehydration (DEH, 88.7+/-6.4%; REH, 90.6+/
      6.1% (P>0.05)). Quadriceps peak torque was significantly elevated in both trials
      prior to the TT (P<0.05), while a 19% increase in the rate of potentiated peak
      twitch torque development (P<0.05) was observed in the DEH trial only. All other
      neuromuscular measures were similar between trials. Short duration TT performance
      and neuromuscular function are not reduced by dehydration, independent of
      hyperthermia.

PMID- 24577861
TI  - The reliability and adaptive responses of gross efficiency in hot ambient
      conditions.
AB  - This study evaluated the reliability and adaptive responses of cycling gross
      efficiency (GE) performed at different intensities, across 3 trials in simulated
      hot (~30 degrees C) temperatures. Twelve cyclists performed 3 hot (30+/-0.7oC and
      RH of 50+/-2.9%) GE sessions, comprising 3 sub-maximal work rates of 150 W, 200 W
      and 250 W (5-min each), separated by 24-h. Paired t-tests revealed no changes
      (P>0.05) in GE between trials. 95% limits of agreement demonstrated random error
      in GE ranging from 1.71% (250 W; trials 1-2) to 2.32% (200 W; trials 1-2),
      leading to a total error of -2.45%. The coefficient of variation (CV%) ranged
      from 3.1+/-0.4% (250 W; trials 1-2) to 4.0+/-0.5% (200 W; trials 1-2). Among non
      acclimated, well-trained cyclists, GE did not change between consecutive
      submaximal cycling bouts performed in the heat. The reliability of GE when
      cycling in the heat (CV=3.1-4.0%) is similar to that reported among cyclists in
      thermoneutral environments. Whilst the interpretation of GE reliability was
      dependent on the adopted statistical technique, it can be small enough to detect
      typical changes owing to heat exposure. 

PMID- 24577862
TI  - Jumper's knee or lander's knee? A systematic review of the relation between jump
      biomechanics and patellar tendinopathy.
AB  - Patellar tendinopathy (jumper's knee) is a common injury in sports that comprise
      jump actions. This article systematically reviews the literature examining the
      relation between patellar tendinopathy and take-off and landing kinematics in
      order to uncover risk factors and potential prevention strategies. A systematic
      search of the Pubmed, Embase and Amed databases was performed to identify studies
      that reported kinematics of sport specific jumps in relation to patellar
      tendinopathy. A quantitative analysis was performed on 4 indentified studies.
      Differences were found only between controls and asymptomatic subjects with
      patellar tendon abnormalities. Most differences were found during horizontal
      landing after forward acceleration. A synthesis of the literature suggests that
      horizontal landing poses the greatest threat for developing patellar
      tendinopathy. A stiff movement pattern with a small post-touchdown range of
      motion and short landing time is associated with the onset of patellar
      tendinopathy. Accordingly, employing a flexible landing pattern seems to be an
      expedient strategy for reducing the risk for (re-) developing patellar
      tendinopathy. Together, these findings indicate that improving kinetic chain
      functioning, performing eccentric exercises and changing landing patterns are
      potential tools for preventive and/or therapeutic purposes. 

PMID- 24577863
TI  - A cross-sectional study of the plantar flexor muscle and tendon during growth.
AB  - The purpose of this study was to investigate growth changes in human plantar
      flexor muscle and tendons. In addition, we ascertained whether growth changes in
      muscle and tendon were more closely related to skeletal age than chronological
      age. 22 elementary school children (ESC), 19 junior high school students (JHS),
      and 23 young adults (ADT) men participated in this study. Maximal strain and
      hysteresis of tendon structures and cross-sectional area of Achilles tendon were
      measured using ultrasonography. In addition, skeletal age was assessed using
      Tanner-Whitehouse III method. Maximal strain of ESC was significantly greater
      than that of other groups, while no significant difference was observed between
      JHS and ADT. There was no difference in hysteresis among 3 groups. Relative cross
      sectional area (to body mass(2/3)) of ADT was significantly smaller than that of
      other groups. For ESC and JHS, measured variables of muscle and tendon were
      significantly correlated to both chronological and skeletal ages. These results
      suggested that immature musculoskeletal system was protected by more extensible
      and larger tendon structures in ESC and only by larger tendon structures in JHS,
      respectively. Furthermore, there were no differences in correlation coefficient
      values between measured variables of muscle and tendon and chronological or
      skeletal ages. 

PMID- 24577864
TI  - Association of acceleration with spatiotemporal variables in maximal sprinting.
AB  - This study clarified the association between acceleration and the rates of
      changes in spatiotemporal variables on a step-to-step basis during the entire
      acceleration phase of maximal sprinting. 21 male sprinters performed a 60-m
      sprint, during which step-to-step acceleration and rates of changes in step
      length (RSL) and step frequency (RSF) were calculated. The coefficients of
      correlation between acceleration and other variables were tested at each step.
      There were positive correlations between acceleration and the RSF up to the
      second step. Acceleration was positively correlated with the RSL from the 5(th)
      to the 19(th) step. At the third and from the 16(th) to the 22(nd) step and from
      the 20(th) to the 21(st) step, there was no significant correlation, but weak
      relationships were found between acceleration and the RSF and RSL. The results
      suggest that the acceleration phase can be divided into 3 sections, and for
      sprinting to be effective, it is important to accelerate by increasing the step
      frequency to the third step, increasing the step length from the 5(th) to the
      15(th) step, and increasing the step length or frequency (no systematic relative
      importance of step length or frequency) from the 16(th) step in the entire
      acceleration phase. 

PMID- 24577865
TI  - Synchronous alteration pattern between serine-threonine kinase receptor
      associated protein and Smad7 in pilocarpine-induced rats of epilepsy.
AB  - PURPOSE: Recent studies have shown that transforming growth factor beta (TGFbeta)
      signaling participates in the epileptogenesis. Serine-threonine kinase receptor
      associated protein (STRAP) and Smad7 synergize in the inhibition of the TGFbeta
      signaling. The aim of the present study was to determine the expression pattern
      of STRAP and Smad7 in the hippocampus and temporal lobe cortex of pilocarpine
      induced rats models of epilepsy. METHODS: Lithium chloride-pilocarpine-induced
      rats with status epilepticus (SE) were established. Total of 60 male Sprague
      Dawley rats was used as control (n = 10), 24 h (n = 10), 72 h (n = 10), 1 week (n
      = 10), 1 month (n = 10), and 2 months (n = 10) after pilocarpine-induced SE,
      respectively. We detected the expression levels of STRAP and Smad7 in the
      hippocampus and temporal lobe cortex of rats at the aforementioned time points
      using western blotting and immunohistochemistry. RESULTS: STRAP level was
      significantly decreased in 24 h, 72 h (acute stage), 1 week (latent stage), 1
      month, 2 months (chronic stage), respectively, in the rat models compared with
      the control rats by using both western blotting and immunohistochemistry. Smad7
      had similar reduced pattern as STRAP. CONCLUSIONS: Our results indicate that
      STRAP and Smad7 proteins might be involved in the development of temporal lobe
      epilepsy.

PMID- 24577867
TI  - A theoretical model of health-related outcomes of resilience in middle
      adolescents.
AB  - There is a dearth of knowledge about the health outcomes of resilience during
      adolescence, making the study of health-related outcomes of resilience important.
      The purpose of this study was to develop a theory-based just-identified model and
      to test the direct and indirect effects of resilience on hope, well-being, and
      health-promoting lifestyle in middle adolescents. The study used a correlational
      design. The final sample consisted of 311 middle adolescents, aged 15 to 17, who
      were recruited from a public high school. Participants responded to instrument
      packets in classroom settings. The structural equation model was tested with the
      LISREL 8.80 software program. All seven hypotheses were supported at a
      statistically significant level (p < .001). The results supported the theoretical
      propositions and the previous empirical findings that were used to create the
      theoretical model of health-related outcomes of resilience. Alternate models of
      outcomes of resilience need to be tested on adolescents. 

PMID- 24577868
TI  - Electronic measurement of medication adherence.
AB  - The measurement of medication adherence is important in both clinical practice
      and research settings to offer effective medical therapy, improve clinical
      outcomes, and determine the efficacy of therapy. The aims of this article are to
      (a) present an overview of current and developing electronic methods of
      medication measurement, (b) explore the advantages and disadvantages to each
      approach, and (c) discuss the implications of using electronic monitoring devices
      for clinical practice and research. A comprehensive review of electronic forms of
      medication measurement was performed. A description of each method is presented
      including oral medication monitors, personal electronic devices, electronic
      blisters, wirelessly observed therapy, inhaled medication monitors, mobile
      phones, video/photo-assisted observation, and electronic health records.
      Familiarity with using electronic devices and advances in technology will
      continue to develop and influence the measurement of medication adherence. 

PMID- 24577866
TI  - State of the science: depression and type 2 diabetes.
AB  - Depression is a significant comorbid condition in diabetes. Individuals with type
      2 diabetes (T2DM) are 2 times more likely to experience depression or elevated
      depressive symptoms compared to those without T2DM. The aims of this state of the
      science review were to summarize the putative links between diabetes and
      depression and review empirically supported treatments of depression in diabetes.
      Findings suggest that a bidirectional association between depression and T2DM
      exists and that several biological and psychosocial mediators underlie these
      conditions. Available data indicate that conventional treatments (antidepressant
      medication, cognitive behavioral therapy, and collaborative care) reduce
      depression and symptoms of depression; however more controlled studies and
      development of novel therapies are needed. Glycemic outcomes have most frequently
      been examined, but findings have been mixed. Self-care and adherence outcomes
      have been less well studied. Emerging evidence suggests that these outcomes may
      be important targets for future depression research in T2DM. 

PMID- 24577869
TI  - Test of a Process Evaluation Checklist to improve neonatal pain practices.
AB  - The Evidence-Based Practice Identification and Change (EPIC) strategy is a
      multifaceted knowledge translation intervention. Although the intervention
      promoted evidence-based practice, the process of delivering the intervention
      components is not well understood. The purpose of this study was to determine the
      construct validity of the Process Evaluation Checklist developed for monitoring
      the fidelity of implementing the intervention to improve neonatal pain practices
      (i.e., documentation of ordering and administration of sucrose). A case study
      design was used. A research practice council in a single Neonatal Intensive Care
      Unit implemented the intervention. The Process Evaluation Checklist was used to
      record adherence in carrying out the intervention components. A significant
      improvement in the documentation of sucrose orders (p = .002) and administration
      (p = .004) provided evidence of the construct validity of this intervention
      fidelity measure. Using this measure in different contexts over longer periods of
      time will further validate the Process Evaluation Checklist. 

PMID- 24577870
TI  - Toxic epidermal necrolysis-like lesions as a manifestation of lupus
      erythematosus: the clinical picture of two cases.

PMID- 24577871
TI  - Quantitative evaluation of phonomicrosurgical manipulations using a magnetic
      motion tracking system.
AB  - OBJECTIVES/HYPOTHESIS: To present and evaluate the magnetic-based
      phonomicrosurgery instrument tracking system, a novel and objective method of
      acquiring instrument position data during simulated phonomicrosurgery. The
      position data can be used to compute quantitative motion metrics. This system was
      used to objectively evaluate the motion performance of novice and expert surgeons
      during phonomicrosurgical simulations and determine the differences between these
      groups. STUDY DESIGN: Prospective cohort study. METHODS: A magnetic-based
      phonomicrosurgery instrument tracking system was developed, including a
      workbench, independent task, motion metrics, and computer program. Based on this
      system, three experts' and six novices' motion data were collected and analyzed.
      RESULTS: Experts demonstrated significantly better motion smoothness along the y
      axis for the dominant hand. For the nondominant hand, experts demonstrated better
      motion smoothness along all three axes, shorter path length, and better depth
      perception (P < .05). Experts also demonstrated higher quality of operation (P <
      .001). No significant difference in time was noted (P = .671). CONCLUSIONS:
      Parameters derived from magnetic-based motion tracking were able to differentiate
      between expert and novice surgeons. These parameters have the potential to be
      used in phonomicrosurgical training as feedback to enhance the training process.

PMID- 24577872
TI  - Prediction of hydration free energies for the SAMPL4 data set with the AMOEBA
      polarizable force field.
AB  - Hydration free energy calculations are often used to validate molecular
      simulation methodologies and molecular mechanics force fields. We use the free
      energy perturbation method together with the AMOEBA polarizable force field and
      the Poltype parametrization protocol to predict the hydration free energies of 52
      molecules as part of the SAMPL4 blind challenge. For comparison, similar
      calculations are performed using the non-polarizable General Amber force field.
      Against our expectations, the latter force field gives the better results
      compared to experiment. One possible explanation is the sensitivity of the AMOEBA
      results to the conformation used for parametrization. 

PMID- 24577873
TI  - Reinforcing the membrane-mediated mechanism of action of the anti-tuberculosis
      candidate drug thioridazine with molecular simulations.
AB  - Thioridazine is a well-known dopamine-antagonist drug with a wide range of
      pharmacological properties ranging from neuroleptic to antimicrobial and even
      anticancer activity. Thioridazine is a critical component of a promising multi
      drug therapy against M. tuberculosis. Amongst the various proposed mechanisms of
      action, the cell membrane-mediated one is peculiarly tempting due to the
      distinctive feature of phenothiazine drug family to accumulate in selected body
      tissues. In this study, we employ long-scale molecular dynamics simulations to
      investigate the interactions of three different concentrations of thioridazine
      with zwitterionic and negatively charged model lipid membranes. Thioridazine
      partitions into the interfacial region of membranes and modifies their structural
      and dynamic properties, however dissimilarly so at the highest membrane-occurring
      concentration, that appears to be obtainable only for the negatively charged
      bilayer. We show that the origin of such changes is the drug induced decrease of
      the interfacial tension, which ultimately leads to the significant membrane
      expansion. Our findings support the hypothesis that the phenothiazines
      therapeutic activity may arise from the drug-membrane interactions, and reinforce
      the wider, emerging view of action of many small, bioactive compounds. 

PMID- 24577874
TI  - A phase 2, single-arm study of ramucirumab in patients with metastatic renal cell
      carcinoma with disease progression on or intolerance to tyrosine kinase inhibitor
      therapy.
AB  - BACKGROUND: Multitargeted tyrosine kinase inhibitors (TKIs) have antitumor
      activity in metastatic renal cell carcinoma (mRCC). Resistance to these agents
      develops frequently, and their use is often limited by intolerance. Ramucirumab
      is a recombinant human monoclonal antibody directed against human vascular
      endothelial growth factor receptor-2. For this study, the authors investigated
      the clinical efficacy and safety of ramucirumab in patients with TKI
      resistant/intolerant mRCC. METHODS: In this single-arm phase 2 trial, patients
      received ramucirumab 8 mg/kg every 2 weeks until they developed disease
      progression or intolerable toxicity. The primary endpoint was the best objective
      response rate (ORR); additional endpoints included the disease control rate
      (DCR), progression-free survival (PFS), the median duration of overall response,
      and safety. RESULTS: Thirty-nine patients with RCC received ramucirumab
      monotherapy. Prior TKI therapy included sunitinib (59% of patients), sunitinib
      and sorafenib (30.8% of patients), and sorafenib (10.3% of patients). The ORR was
      5.1% (95% confidence interval [CI], 0.6%-17.3%). The 12-week DCR was 64.1% (95%
      CI, 47.2%-78.8%). The median PFS was 7.1 months (95% CI, 4.1-9.7 months), and the
      median overall survival was 24.8 months (95% CI, 18.9-32.6 months). Grade 3 or
      higher adverse events that occurred in >=5% of patients included grade 3
      hypertension (7.7%) and proteinuria (5.1%). There was 1 on-study death from
      multiorgan failure. CONCLUSIONS: Although the study did not meet its primary
      endpoint of >=15% ORR, ramucirumab was associated with evidence of antitumor
      activity in patients with TKI-resistant/intolerant mRCC. Ramucirumab was safe and
      well tolerated.

PMID- 24577875
TI  - Role of the basement membrane in regulation of cardiac electrical properties.
AB  - In the heart muscle, each adult cardiomyocyte is enclosed by a basement membrane
      (BM). This innermost extracellular matrix is a layered assembly of laminin,
      collagen IV, glycoproteins, and proteoglycans. In this study, the role of the BM
      network in regulation of the electrical properties of neonatal cardiomyocytes
      (NCMs) cultured on an aligned collagen I gel was investigated using a
      multielectrode array (MEA). A laminin antibody was added to the culture medium
      for 48-120 h to conjugate newly secreted laminin. Then, morphology of the NCMs on
      an MEA was monitored using a phase contrast microscope, and the BM network that
      was immunocytostained for laminin was imaged using a fluorescence microscope.
      When the BM laminin was absent in this culture model, dramatic changes in NCM
      morphology were observed. Simultaneously, the MEA-recorded cardiac field
      potential showed changes compared to that from the control groups: The period of
      contraction shortened to 1/2 of that from the control groups, and the waveform of
      the calcium influx shifted from a flat plateau to a peak-like waveform,
      indicating that the electrical properties of the NCMs were closely related to the
      components and distribution of the BM network. 

PMID- 24577877
TI  - A feedforward model for the formation of a grid field where spatial information
      is provided solely from place cells.
AB  - Grid cells (GCs) in the medial entorhinal cortex (mEC) have the property of
      having their firing activity spatially tuned to a regular triangular lattice.
      Several theoretical models for grid field formation have been proposed, but most
      assume that place cells (PCs) are a product of the grid cell system. There is,
      however, an alternative possibility that is supported by various strands of
      experimental data. Here we present a novel model for the emergence of gridlike
      firing patterns that stands on two key hypotheses: (1) spatial information in GCs
      is provided from PC activity and (2) grid fields result from a combined synaptic
      plasticity mechanism involving inhibitory and excitatory neurons mediating the
      connections between PCs and GCs. Depending on the spatial location, each PC can
      contribute with excitatory or inhibitory inputs to GC activity. The nature and
      magnitude of the PC input is a function of the distance to the place field
      center, which is inferred from rate decoding. A biologically plausible learning
      rule drives the evolution of the connection strengths from PCs to a GC. In this
      model, PCs compete for GC activation, and the plasticity rule favors efficient
      packing of the space representation. This leads to gridlike firing patterns. In a
      new environment, GCs continuously recruit new PCs to cover the entire space. The
      model described here makes important predictions and can represent the
      feedforward connections from hippocampus CA1 to deeper mEC layers. 

PMID- 24577876
TI  - Prenatal phthalate exposures and neurobehavioral development scores in boys and
      girls at 6-10 years of age.
AB  - BACKGROUND: There is concern over potential neurobehavioral effects of prenatal
      phthalate exposures, but available data are inconsistent. OBJECTIVES: We examined
      associations between prenatal urinary concentrations of phthalate metabolites and
      neurobehavioral scores among children. METHODS: We measured phthalate metabolite
      concentrations in urine samples from 153 pregnant participants in the Study for
      Future Families, a multicenter cohort study. Mothers completed the Child Behavior
      Checklist when the children were 6-10 years of age. We estimated overall and sex
      specific associations between phthalate concentrations and behavior using
      adjusted multiple regression interaction models. RESULTS: In boys, concentrations
      of monoisobutyl phthalate were associated with higher scores for inattention
      (beta = 0.27; 95% CI: 0.04, 0.50), rule-breaking behavior (beta = 0.20; 95% CI:
      0.01, 0.38), aggression (beta = 0.34; 95% CI: 0.09, 0.59), and conduct problems
      (beta = 0.39; 95% CI: 0.20, 0.58), whereas the molar sum of di(2-ethylhexyl)
      phthalate metabolites was associated with higher scores for somatic problems
      (beta = 0.15; 95% CI: 0.03, 0.28). Higher monobenzyl phthalate concentrations
      were associated with higher scores for oppositional behavior (beta = 0.16; 95%
      CI: 0.01, 0.32) and conduct problems (beta = 0.21; 95% CI: 0.06, 0.37) in boys,
      but with reduced anxiety scores in girls (beta = -0.20; 95% CI: -0.39, -0.01). In
      general, the associations reported above were close to the null among girls.
      Model coefficients represent the difference in the square root-transformed
      outcome score associated with a 1-unit increase in log-transformed metabolites.
      CONCLUSIONS: Our results suggest associations between exposure to certain
      phthalates in late pregnancy and behavioral problems in boys. Given the few
      studies on this topic and methodological and population differences among
      studies, additional research is warranted.

PMID- 24577878
TI  - Effect of cardiac rehabilitation on functional and emotional status in patients
      after transcatheter aortic-valve implantation.
AB  - BACKGROUND: Transcatheter aortic-valve implantation (TAVI) is an established
      alternative therapy in patients with severe aortic stenosis and a high surgical
      risk. Despite a rapid growth in its use, very few data exist about the efficacy
      of cardiac rehabilitation (CR) in these patients. We assessed the hypothesis that
      patients after TAVI benefit from CR, compared to patients after surgical aortic
      valve replacement (sAVR). METHODS: From September 2009 to August 2011, 442
      consecutive patients after TAVI (n = 76) or sAVR (n = 366) were referred to a 3
      week CR. Data regarding patient characteristics as well as changes of functional
      (6-min walk test. 6-MWT), bicycle exercise test), and emotional status (Hospital
      Anxiety and Depression Scale) were retrospectively evaluated and compared between
      groups after propensity score adjustment. RESULTS: Patients after TAVI were
      significantly older (p < 0.001), more female (p < 0.001), and had more often
      coronary artery disease (p = 0.027), renal failure (p = 0.012) and a pacemaker (p
      = 0.032). During CR, distance in 6-MWT (both groups p <= 0.001) and exercise
      capacity (sAVR p <= 0.001, TAVI p <= 0.05) significantly increased in both
      groups. Only patients after sAVR demonstrated a significant reduction in anxiety
      and depression (p <= 0.001). After propensity scores adjustment, changes were not
      significantly different between sAVR and TAVI, with the exception of 6-MWT (p =
      0.004). CONCLUSIONS: Patients after TAVI benefit from cardiac rehabilitation
      despite their older age and comorbidities. CR is a helpful tool to maintain
      independency for daily life activities and participation in socio-cultural life.

PMID- 24577879
TI  - Laparoscopic sleeve gastrectomy using 42-French versus 32-French bougie: the
      first-year outcome.
AB  - BACKGROUND: The optimal size of bougie in laparoscopic sleeve gastrectomy (LSG)
      remains controversial. The aim of this study was to evaluate the first-year
      outcome of LSG using two different sizes of bougies. METHODS: This study used a
      single institute retrospective case-control study of two groups of patients.
      Group A (N = 66) underwent LSG using 42-Fr and group B (N = 54) using 32-Fr
      bougies. A medication score was applied to assess the change in comorbid
      conditions. RESULTS: Groups A and B's age (39.5 +/- 12 vs. 43.6 +/- 12.3 years),
      weight (119 +/- 17 vs. 120 +/- 20), and BMI (42.8 +/- 3.8 vs. 43.6 +/- 6.9
      kg/m(2)), respectively, were comparable (p = NS). Comorbid conditions were type 2
      diabetes (T2DM) in 19 (29%) vs. 23 (43%) patients, hypertension in 22 (33%) vs.
      18 (33%) patients, and gastroesophageal reflux (GERD) in 28 (42%) vs. 10 (19%)
      patients, respectively. At 1 year, group A vs. B BMI was (29.4 +/- 5 vs. 30 +/- 5
      kg/m(2)) and excess weight loss was 67 vs. 65%, respectively (p = NS).
      Postoperatively, T2DM (79 vs. 83%), hypertension (82 vs. 61%), and GERD (82 vs.
      60%) (p = NS), respectively, in groups A vs. B did not require previous
      medications anymore. Complications were comparable. CONCLUSIONS: Our data suggest
      that using a 42-Fr or 32-Fr bougie does not influence LSG first-year weight loss
      or resolution of comorbid conditions. Long-term data is needed to conclude this
      issue.

PMID- 24577880
TI  - Psychodynamic psychotherapy versus cognitive behavior therapy for social anxiety
      disorder: an efficacy and partial effectiveness trial.
AB  - OBJECTIVES: Comparing the overall and differential effects of psychodynamic
      psychotherapy (PDT) versus cognitive behavior therapy (CBT) for social anxiety
      disorder (SAD). DESIGN: Patients with a primary SAD (N = 47) were randomly
      assigned to PDT (N = 22) or CBT (N = 27). Both PDT and CBT consisted of up to 36
      sessions (average PDT 31.4 and CBT 19.8 sessions). Assessments took place at
      waitlist: pretest, after 12 and 24 weeks for those who received longer treatment:
      posttest, 3-month and 1-year follow-up. METHODS: Changes in the main outcome
      measure self-reported social anxiety composite, as well as in other
      psychopathology, social skills, negative social beliefs, public self
      consciousness, defense mechanisms, personal goals, independent rater's judgments
      of SAD and general improvement, and approach behavior during an objective test,
      were analyzed using multilevel analysis. RESULTS: No improvement occurred during
      waitlist. Treatments were highly efficacious, with large within-subject effect
      sizes for social anxiety, but no differences between PDT and CBT on general and
      treatment-specific measures occurred. Remission rates were over 50% and similar
      for PDT and CBT. Personality disorders did not influence the effects of PDT or
      CBT. CONCLUSIONS: PDT and CBT are both effective approaches for SAD. Further
      research is needed on the cost-effectiveness of PDT versus CBT, on different
      lengths PDT, and on patient preferences and their relationship to outcome of PDT
      versus CBT.

PMID- 24577882
TI  - How to prevent diplopia in endoscopic transnasal resection of tumors involving
      the medial orbital wall.

PMID- 24577883
TI  - EORTC QLQ-C15-PAL quality of life score as a prognostic indicator of survival in
      patients with far advanced cancer.
AB  - PURPOSE: Quality of life (QoL) and performance status predict survival in
      advanced cancer patients; these relationships have not been explored in the
      hospice palliative care setting. The aim of this study was to examine the
      survival predictability of patient-reported QoL using the European Organization
      for Research and Treatment of Cancer (EORTC) QLQ-C15-PAL questionnaire in far
      advanced cancer inpatients at the very end of life. METHODS: This is a
      retrospective cohort study. Patients reported QoL using the EORTC QLQ-C15-PAL.
      One hundred sixty-two inpatients in hospice palliative wards of six hospitals in
      South Korea were followed until death or the end of the study. Additional
      symptoms and performance status were assessed by the MD Anderson Symptom
      Inventory-Korean (MDASI-K), Palliative Performance Scale (PPS) and Eastern
      Cooperative Oncology Group (ECOG) performance status. Correlations between EORTC
      QLQ-C15-PAL, MDASI-K, PPS, and ECOG were assessed. Survival analyses were
      performed using Cox proportional hazard models. RESULTS: Patients' median
      survival was less than 1 month. Physician-reported PPS significantly predicted
      survival (hazard ratio [HR] 0.493; p<0.001). From the EORTC QLQ-C15-PAL, patient
      reported physical functioning predicted survival (HR=0.65; p<0.001). Other six
      domains of EORTC QLQ-C15-PAL were significantly related to survival after
      adjustment. Those domains were global health status, emotional functioning,
      fatigue, nausea/vomiting, appetite loss, and constipation. CONCLUSIONS: EORTC QLQ
      C15-PAL can be an independent prognostic factor in inpatients with far advanced
      cancer. Patient-reported physical functioning showed survival predictability as
      good as physician-reported performance status. It is notable that the QLQ
      instrument is useful even for patients in their final month of life. Cancer
      anorexia-cachexia syndrome-related symptoms may be independent prognostic
      symptoms. Prospective study is warranted.

PMID- 24577881
TI  - Oxidative stress, T cell DNA methylation, and lupus.
AB  - OBJECTIVE: Lupus develops when genetically predisposed people encounter
      environmental agents, such as ultraviolet light, silica, infections, and
      cigarette smoke, that cause oxidative stress, but how oxidative damage modifies
      the immune system to cause lupus flares is unknown. We previously showed that
      inhibiting DNA methylation in CD4+ T cells by blocking ERK pathway signaling is
      sufficient to alter gene expression, and that the modified cells cause lupus-like
      autoimmunity in mice. We also reported that T cells from patients with active
      lupus have decreased ERK pathway signaling, have decreased DNA methylation, and
      overexpress genes normally suppressed by DNA methylation. This study was
      undertaken to test whether oxidizing agents decrease ERK pathway signaling in T
      cells, decrease DNA methyltransferase levels, and cause demethylation and
      overexpression of T cell genes similar to that found in T cells from patients
      with active lupus. METHODS: CD4+ T cells were treated with the oxidizers H2 O2 or
      ONOO(-) . Effects on ERK pathway signaling were measured by immunoblotting, DNA
      methyltransferase 1 (DNMT-1) levels were measured by reverse transcriptase
      polymerase chain reaction (RT-PCR), and the methylation and expression of T cell
      genes were measured using flow cytometry, RT-PCR, and bisulfite sequencing.
      RESULTS: H2 O2 and ONOO(-) inhibited ERK pathway signaling in T cells by
      inhibiting the upstream regulator protein kinase Cdelta, decreased DNMT-1 levels,
      and caused demethylation and overexpression of genes previously shown to be
      suppressed by DNA methylation in T cells from patients with active lupus.
      CONCLUSION: Our findings indicate that oxidative stress may contribute to human
      lupus flares by inhibiting ERK pathway signaling in T cells to decrease DNMT-1
      and cause DNA demethylation.

PMID- 24577886
TI  - Abstracts of the 10th Annual Congress of the European Cardiac Arrhythmia Society,
      March 23-25, 2014, Munich, Germany.

PMID- 24577884
TI  - Changes in thyroid hormone receptors after permanent cerebral ischemia in male
      rats.
AB  - Thyroid hormones (TH) and receptors (TRs) may play an important role in the
      pathophysiology of acute cerebral ischemia. In the present study, we sought to
      determine whether serum triodothyronine (T3)/thyroxine (T4) and brain TRs
      (TRalpha1, TRbeta1) might change after experimental stroke. Male adult Wistar
      rats were subjected to permanent middle cerebral artery occlusion (group P) and
      compared to sham-operated controls (group S). Animals were followed clinically
      for 14 days until brain collection for Western blot (WB) or neuropathological
      analysis of TRs in three different brain areas (infarcted tissue, E1;
      noninfarcted ipsilateral hemisphere, E2; and contralateral hemisphere, E3).
      Analysis of serum TH levels showed a reduction of T4 in group P (p = 0.002) at
      days 2 to 14, while half of the animals also displayed "low T3" values (p =
      0.012) on day 14. This T4 reduction was inversely correlated to the clinical
      severity of stroke and the concomitant body weight loss (p < 0.005). WB analysis
      of TRalpha1 and TRbeta1 protein expression showed heterogenic responses at day
      14: total and nuclear TRalpha1 were similar between the two groups, while total
      TRbeta1 decreased 7.5-fold within E1 (p <= 0.001) with a concomitant 1.8-fold
      increase of nuclear TRbeta1 in E2 area (p = 0.03); TRbeta1 expression did not
      differ in E3. Neuropathological analysis revealed that activated
      macrophages/microglia exclusively expressed nuclear TRalpha1 within the infarct
      core. Astrocytes mildly expressed nuclear TRalpha1 in and around the infarct,
      along with a prominent TRbeta nuclear signal restricted in the astrocytic scar.
      Neurons around the infarct expressed mainly TRalpha1 and, to a milder degree,
      TRbeta. Surprisingly enough, we detected for the first time a TRbeta expression
      in the paranodal region of Ranvier nodes, of unknown significance so far. Our
      data support that cerebral ischemia induces a low TH response, associated with
      significant and heterogenic changes in brain TR expression. These findings could
      imply an important role of TH signaling in cerebral ischemia.

PMID- 24577887
TI  - Ramucirumab in metastatic renal cell carcinoma: The beginning or the end?

PMID- 24577885
TI  - Antibodies directed to the gram-negative bacterium Neisseria gonorrhoeae cross
      react with the 60 kDa heat shock protein and lead to impaired neurite outgrowth
      in NTera2/D1 cells.
AB  - Children of mothers with prenatal gonococcal infections are of increased risk to
      develop schizophrenic psychosis in later life. The present study hypothesizes an
      autoimmune mechanism for this, investigating interactions of a commercial rabbit
      antiserum directed to Neisseria gonorrhoeae (alpha-NG) with human NTera2/D1
      cells, an established in vitro model for human neuronal differentiation.
      Immunocytochemistry demonstrated alpha-NG to label antigens on an intracellular
      organelle, which by Western blot analysis showed a molecular weight shortly below
      72 kDa. An antiserum directed to Neisseria meningitidis (alpha-NM) reacts with an
      antigen shortly below 95 kDa, confirming antibody specificity of these
      interactions. Two-dimensional gel electrophoresis and partial Western transfer,
      allowed to localize an alpha-NG reactive protein spot which was identified by LC
      Q-TOF MS/MS analysis as mitochondrial heat shock protein Hsp60. This was
      confirmed by Western blot analysis of alpha-NG immunoreactivity with a commercial
      Hsp60 protein sample, with which alpha-NM failed to interact. Finally, analysis
      of neurite outgrowth in retinoic acid-stimulated differentiating NTera2-D1 cells,
      demonstrates that alpha-NG but not alpha-NM treatment reduces neurite length.
      These results demonstrate that alpha-NG can interact with Hsp60 in vitro, whereas
      pathogenetic relevance of this interaction for psychotic symptomatology remains
      to be clarified.

PMID- 24577888
TI  - A fluorescent sensor for highly selective detection of nitroaromatic explosives
      based on a 2D, extremely stable, metal-organic framework.
AB  - A 2D, extremely stable, metal-organic framework (MOF), NENU-503, was successfully
      constructed. It displays highly selective and recyclable properties in detection
      of nitroaromatic explosives as a fluorescent sensor. This is the first MOF that
      can distinguish between nitroaromatic molecules with different numbers of ?NO2
      groups. 

PMID- 24577889
TI  - The Glu298Asp polymorphism in the NOS3 gene and the risk of prostate cancer.
AB  - The Glu298Asp polymorphism in the NOS3 gene has been implicated as a risk factor
      for prostate cancer. To date, several studies have evaluated the associations
      between the Glu298Asp polymorphism and prostate cancer risk; however, the results
      were inconclusive. The aim of the current study was to perform a meta-analysis to
      investigate the association between the polymorphism and the risk of prostate
      cancer. A total of 3,206 cases and 3,880 controls from eight case-control studies
      were included for data synthesis. The overall results suggested no significant
      association between the polymorphism and the risk of prostate cancer (OR=1.01,
      95% CI=0.92-1.11, p = 0.83 for Asp/Asp+Glu/Asp vs. Glu/Glu). In the stratified
      analysis according to ethnicity, no significant associations were observed in
      Asians and Europeans. The current meta-analysis suggested that the Glu298Asp
      polymorphism of the NOS3 gene might not contribute to the risk of prostate
      cancer.

PMID- 24577890
TI  - Association between CLPTM1L-TERT rs401681 polymorphism and pancreatic cancer risk
      among Chinese Han population.
AB  - Pancreatic cancer is one of the human cancers with the highest fatality rates;
      however, the etiology still remains largely unknown. Recently, one genome-wide
      association study (GWAS), conducted exclusively among women of European ancestry,
      has discovered that cleft lip and palate transmembrane 1-like telomerase reverse
      transcriptase (CLPTM1L-TERT) rs401681 polymorphism was significantly associated
      with pancreatic cancer risk. Few studies have been conducted to evaluate whether
      this finding could be generalized to Chinese people. In the current study, we
      explored the association between rs401681 polymorphism and risk of pancreatic
      cancer in a case-control study of 1,587 Chinese people (including 766 pancreatic
      cancer cases and 821 healthy controls). Under the log-additive model, each
      additional copy of minor allele T was associated with a 1.24-fold increased risk
      of pancreatic cancer (odds ratio (OR)=1.24, 95 % confidence interval (CI) 1.06
      1.44, P=5.61 * 10(-3)). While compared with individuals with the CC genotype, the
      OR for developing pancreatic cancer was 1.09 (95 % CI 0.88-1.34) among those with
      the CT genotype and 1.66 (95 % CI 1.20-2.29) among those with the TT genotype.
      Additional adjustments for the confounding factors did not change the results
      materially. Our data suggests that the T allele of rs401681 in CLPTM1L-TERT locus
      predisposes its carriers to pancreatic cancer, and further research into the
      function of CLPTM1L-TERT locus and its potential biological mechanism association
      may be warranted.

PMID- 24577893
TI  - Upregulation of serum vascular endothelial growth factor and matrix
      metalloproteinase-3 in patients with oral squamous cell carcinoma.
AB  - Vascular endothelial growth factor (VEGF) is known as a fundamental regulator of
      angiogenesis that accelerates cellular proliferation, vascular permeability, and
      endothelial cell migration and is an inhibitor of apoptosis. Extracellular matrix
      degradation by matrix metalloproteinase (MMP) is necessary for endothelial cell
      proliferation, migration, and metastasis. Accordingly, the objective of the
      present study was to determine the circulating levels of VEGF and MMP3 and their
      relation in patients with oral squamous cell carcinoma. Using an ELISA kit, the
      circulating levels of VEGF and MMP-3 in the sera of 45 patients with oral
      squamous cell carcinoma (OSCC) and 45 healthy controls were assessed. Mean VEGF
      levels in the sera of patients with OSCC (122.4 +/- 36.1) were significantly
      higher than those in controls (65.3 +/- 23.4); however, no relation was found
      between VEGF levels and clinicopathologic factors. The serum MMP-3 level in OSCC
      patients was significantly higher (9.45 +/- 4.6 ng/ml, n=45) than that in healthy
      controls (5.9 +/- 3.6 ng/ml, n=45). There was no correlation in serum MMP-3
      concentration with clinicopathologic features such as tumor stage, tumor size,
      nodal status, and histological grade. A significant relationship was found
      between serum levels of VEGF and MMP3. This study concludes that VEGF and MMP3
      may have a potential role in the pathogenesis of OSCC but cannot be used as a
      tool for monitoring tumor progression. Moreover, the role of VEGF in the
      regulation of angiogenesis is in part due to activation of MMP-3.

PMID- 24577891
TI  - A systematic review of matrix metalloproteinase 9 as a biomarker of survival in
      patients with osteosarcoma.
AB  - Matrix metalloproteinase 9 (MMP-9) plays an important role in the progression of
      several types of cancer by increasing tumor growth, migration, invasion, and
      metastasis and is associated with poor disease prognosis. The possible prognostic
      value of MMP-9 in osteosarcoma has also been examined, but due to inconsistent
      results between studies, it has not been possible to draw firm conclusions. To
      clarify this issue, we conducted a meta-analysis of published studies to provide
      a comprehensive evaluation of the effect of high MMP-9 expression on the survival
      outcomes of osteosarcoma patients. Seven studies with a total of 339 patients
      with osteosarcoma were examined. The pooled odds ratio (OR) with corresponding 95
      % confidence interval (95 % CI) was calculated to evaluate the effect of MMP-9
      expression on overall survival. Meta-analysis showed that patients with high MMP
      9 expression were significantly associated with lower overall survival when
      compared to their counterparts with low or undetectable MMP-9 expression
      (OR=6.13, 95 % CI 3.45-10.89, P<0.001). Sensitivity analysis suggested the pooled
      OR was stable and not significantly changed when a single study was removed. The
      results from the systematic review and meta-analysis show that MMP-9 is an
      effective biomarker for predicting survival of patients with osteosarcoma.

PMID- 24577894
TI  - APOBEC3 deletion polymorphism is associated with epithelial ovarian cancer risk
      among Chinese women.
AB  - Ovarian cancer remains the leading cause of death from gynecological malignancies
      and the second most common gynecological malignancy among women worldwide.
      However, the etiology still remains largely unknown. Previous studies identified
      APOBEC3 gene deletions were significantly associated with higher breast cancer
      risk in both European and Chinese women. Considering both breast and ovarian
      cancers being hormonally driven and sharing multiple risk factors, we performed
      this case-control study to evaluate the association between APOBEC3 deletion and
      epithelial ovarian cancer (EOC) risk. We analyzed the APOBEC3 deletion in a case
      control study of 2,938 Chinese women (including 1,374 EOC cases and 1,564 healthy
      controls). All participants were genotyped using real-time qualitative PCR
      (qPCR). APOBEC3 deletion was significant associated with EOC risk, with ORs (95 %
      CIs) of 1.46 (1.14-1.86) associated with one copy deletion and 2.53 (0.91-7.06)
      associated with two copy deletion compared with subjects with no deletion (P for
      trend =1.50 * 10(-3)). Additional adjustments and stratified analyses did not
      change the results materially. Our data suggests that the loss genotypes of
      APOBEC3 deletion predispose their carriers to EOC.

PMID- 24577895
TI  - Methylation of tumor suppressor genes in a novel panel predicts clinical outcome
      in paraffin-embedded bladder tumors.
AB  - DNA methylation of tumor suppressor genes (TSGs) represents a frequent and early
      epigenetic event with potential applications for cancer detection and disease
      evolution. Our aim was to examine the stratification and prognostic biomarker
      role of the methylation of a novel panel of TSGs in bladder cancer. The
      methylation status of 18 TSGs was evaluated in bladder cancer cells (n=14) and
      paraffin-embedded primary bladder tumors (n=61), using a methylation-specific
      multiplex ligation-dependent probe amplification assay (MS-MLPA). Recurrence,
      progression, and disease-specific survival were analyzed using univariate and
      multivariate Cox models. PRDM2, HLTF, ID4, DLC1, BNIP3, H2AFX, CACNA1G, TGIF, and
      CACNA1A were discovered methylated in bladder cancer. The methylation of RUNX3
      (p=0.026), TWIST1 (p=0.009), SFRP4 (p=0.002), and CCND2 (p=0.027) correlated to
      tumor stage. Univariate analyses indicated prognostic associations for recurrence
      (DLC1, SFRP5, H2AFX, CACNA1G), progression (DLC1, SFRP5, CACNA1G), disease
      specific (PRDM2, DLC1, SFRP5, CACNA1G, and TIMP3), and overall survival (SFRP5
      and TIMP3). In multivariate analyses, several TSGs remained as independent
      prognosticators for recurrence (SFRP5, H2AFX), progression (CACNA1G), and disease
      specific survival (SFRP5). Thus, a novel set of TSGs was identified, frequently
      methylated in bladder cancer cells and tumors. TSG methylation allowed
      histopathologic and outcome stratification using paraffin-embedded tumors. This
      is clinically relevant by offering a strategy for the management of patients
      affected with uroepithelial neoplasias in pathology routine laboratories.

PMID- 24577896
TI  - Development of high-sensitive ELISA method for detection of adipophilin levels in
      human colostrum and breast milk.
AB  - AIM: To develop and validate high-sensitive (hs) ELISA method for detection of
      adipophilin (adipose differentiation-related protein, ADRP) in human breast milk
      (BM) and to analyze adipophilin levels in BM during 12 months of lactation.
      METHODS: ADRP levels were determined using hsELISA method (Biovendor-Laboratory
      Medicine, Inc.) in colostrum (D0) and BM of 72 mothers was collected 1, 3, 6, and
      12 months following delivery (M1, 3, 6, 12). RESULTS: ADRP was detectable in BM
      up to 12 months of lactation. Mean levels at D0 were 1.98 +/- 0.12; M1, 2.83 +/-
      0.21; M3, 2.39 +/- 0.17; M6, 2.57 +/- 0.16; and at M12 3.25 +/- 0.21 MUg/ml.
      Significantly higher levels of ADRP were found in M1 and M12 when compared to D0
      and in M12 when compared to M3 (overall P = 0.0001). No significant correlation
      was seen between ADRP levels in BM and adiponectin, body weight of infants, their
      birth length, body weight gain during the first year of life, or BMI of mothers
      before pregnancy. CONCLUSIONS: We developed and validated hsELISA for detection
      of ADRP in human BM. ADRP was detectable in human BM during the whole 12 months
      of lactation period and its levels were intraindividually well-conserved.

PMID- 24577897
TI  - Rapid RNA exchange in aqueous two-phase system and coacervate droplets.
AB  - Compartmentalization in a prebiotic setting is an important aspect of early cell
      formation and is crucial for the development of an artificial protocell system
      that effectively couples genotype and phenotype. Aqueous two-phase systems
      (ATPSs) and complex coacervates are phase separation phenomena that lead to the
      selective partitioning of biomolecules and have recently been proposed as
      membrane-free protocell models. We show in this study through fluorescence
      recovery after photobleaching (FRAP) microscopy that despite the ability of such
      systems to effectively concentrate RNA, there is a high rate of RNA exchange
      between phases in dextran/polyethylene glycol ATPS and ATP/poly-L-lysine
      coacervate droplets. In contrast to fatty acid vesicles, these systems would not
      allow effective segregation and consequent evolution of RNA, thus rendering these
      systems ineffective as model protocells. 

PMID- 24577900
TI  - [From the expert's office: Hearing loss of middle and high -frequencies in noise
      induced hearing loss?].

PMID- 24577898
TI  - Involvement of central TRPV1 receptors in pentylenetetrazole and amygdala-induced
      kindling in male rats.
AB  - Transient receptor potential vanilloid 1 (TRPV1) is a non-selective cation
      channel that is involved in modulation of diverse physiological processes. The
      role of this receptor in epilepsy has not been studied well. Therefore, we
      investigated the role of central TRPV1 receptors on the development of
      pentylenetetrazole (PTZ) and amygdala-induced kindling in rats. Male Wistar rats
      received subconvulsive dose of PTZ intraperitoneally, every other day. TRPV1
      receptor agonist, OLDA and its antagonist, AMG-9810 were injected
      intracerebroventricularly 30 min prior to PTZ administration. In electrical
      kindling, stimulating and recording electrodes were implanted in the right
      amygdala of male rats. After kindling, the effect of TRPV1 receptor agonist or
      antagonist on afterdischarge duration (ADD), latency to the onset of bilateral
      forelimb clonuses (S4L) and duration of loss of equilibrium (stage 5 seizures,
      S5D) were measured. The results demonstrated that, OLDA at the doses of 0.01, 0.1
      and 1 MUg/rat, significantly accelerated the incidence of all seizure stages,
      increased S5D and decreased S4L in the PTZ model of kindling. Also, in amygdala
      kindling, S5D and ADD were significantly reduced following the administration of
      AMG-9810. In contrast, OLDA significantly aggravated the indices of seizure in
      both models of epileptic seizure. This study demonstrated that central TRPV1
      receptors may be involved in the development of electrical and PTZ-induced
      kindling.

PMID- 24577901
TI  - [Role of miRNA in malignoma of the head and neck].
AB  - Despite optimized therapeutic strategies, the long-term survival of head and neck
      squamous cell carcinomas (HNSCC) has improved in recent years only slightly. Most
      studies on the tumor cell genome focus on protein-coding genes (exons). Data on
      changes within the non-coding sequences (introns) are limited. miRNAs (microRNA,
      miR) are small non-coding single-stranded RNAs that control gene expression at
      the posttranscriptional level by interacting with the mRNA. miRNA functions
      include many biological processes and control up to 50 % of human genes. They can
      have oncogenic or tumor suppressive functions. Altered expression patterns of
      miRNAs are involved in carcinogenesis and tumor progression even in HNSCC, or
      those processes (increased resistance to radiation or chemotherapy) that could be
      responsible for the poor long-term prognosis by forming metastases and inoperable
      local recurrences. Therefore, we here present miRNA groups, which are involved in
      these processes and may serve as new potential therapeutic treatment targets.
      miRNAs may also serve as biomarkers for early diagnosis, evaluation and
      monitoring of treatment and tumor recurrence. Alterations in miRNA expression
      before and after chemotherapy are therefore of high interest. In the long run,
      this knowledge could lead to more effective therapies with improved therapeutic
      outcome of HNSCC. 

PMID- 24577902
TI  - [Reader's letter].

PMID- 24577903
TI  - [Surgical methods: safe, logical and step by step partial anterior
      ethmoidectomy].

PMID- 24577904
TI  - Multicomponent spectrometric assay of cyanocobalamin and its photoproduct
      hydroxocobalamin in the presence of ascorbic acid in photolyzed solutions.
AB  - The simultaneous determination of cyanocobalamin (CC), hydroxocobalamin (HC) and
      ascorbic acid (AA) in aqueous solution has been achieved by a multicomponent
      spectrometric method. CC undergoes photolysis in acidic and alkaline media to
      form HC and the reaction is enhanced in the presence of AA. The method has been
      used to evaluate the kinetics of photodegradation reactions of the vitamin. CC,
      HC and AA present in the photolyzed solutions have been determined by absorbance
      measurement at 550, 525 and 265 nm at pH 4.0. These wavelengths correspond to the
      absorption maxima of the three substances and thus provide high specificity and
      sensitivity to the method. The method has been validated with respect to various
      parameters relating to the analytical performance characteristics. The recovery
      of the method for the three compounds ranges from 97.1-103.0% with a RSD value of
      +/-3%. The accuracy of the method is shown by the linearity of the kinetic plots
      in the concentration range studied. The method is simple, rapid and convenient
      for the proposed work. 

PMID- 24577905
TI  - Effect of cold water extracts of Acacia modesta Wall. and Glycyrrhiza glabra
      Linn. on Tribolium castaneum and Lemna minor.
AB  - The aim of the present study was to introduce an alternative way for insects
      control through biodegradable plants materials. The different cold water extracts
      dilutions of Acacia modesta and Glycyrrhiza glabra were tested against Tribolium
      castaneum. The extracts dilutions of both plants caused mortality of the
      Tribolium castaneum. ANOVA revealed that dilutions and plants were highly
      significant. The interaction between plants and dilutions was also significant at
      P < 0.05. Phytotoxic activity showed that dilutions of Acacia modesta and
      Glycyrrhiza glabra extracts significantly inhibited the growth of Lemna minor.
      ANOVA showed that dilutions of both plants extracts were significant at P < 0.05.

PMID- 24577906
TI  - Quality evaluation of Houttuynia cordata Thunb. by high performance liquid
      chromatography with photodiode-array detection (HPLC-DAD).
AB  - A new, validated method, developed for the simultaneous determination of 16
      phenolics (chlorogenic acid, scopoletin, vitexin, rutin, afzelin, isoquercitrin,
      narirutin, kaempferitrin, quercitrin, quercetin, kaempferol, chrysosplenol D,
      vitexicarpin, 5-hydroxy-3,3',4',7-tetramethoxy flavonoids, 5-hydroxy-3,4',6,7
      tetramethoxy flavonoids and kaempferol-3,7,4'-trimethyl ether) in Houttuynia
      cordata Thunb. was successfully applied to 35 batches of samples collected from
      different regions or at different times and their total antioxidant activities
      (TAAs) were investigated. The aim was to develop a quality control method to
      simultaneously determine the major active components in H. cordata. The HPLC-DAD
      method was performed using a reverse-phase C18 column with a gradient elution
      system (acetonitrile-methanol-water) and simultaneous detection at 345 nm. Linear
      behaviors of method for all the analytes were observed with linear regression
      relationship (r(2)>0.999) at the concentration ranges investigated. The
      recoveries of the 16 phenolics ranged from 98.93% to 101.26%. The samples
      analyzed were differentiated and classified based on the contents of the 16
      characteristic compounds and the TAA using hierarchical clustering analysis (HCA)
      and principal component analysis (PCA). The results analyzed showed that similar
      chemical profiles and TAAs were divided into the same group. There was some
      evidence that active compounds, although they varied significantly, may possess
      uniform anti-oxidant activities and have potentially synergistic effects. 

PMID- 24577907
TI  - The effect of Centella asiatica, vitamins, glycolic acid and their mixtures
      preparations in stimulating collagen and fibronectin synthesis in cultured human
      skin fibroblast.
AB  - Centella asiatica (Linn.) Urban is well known in promoting wound healing and
      provides significant benefits in skin care and therapeutic products formulation.
      Glycolic acid and vitamins also play a role in the enhancement of collagen and
      fibronectin synthesis. Here, we evaluate the specific effect of Centella asiatica
      (CA), vitamins, glycolic acid and their mixture preparations to stimulate
      collagen and fibronectin synthesis in cultured human fibroblast cells. The
      fibroblast cells are incubated with CA, glycolic acid, vitamins and their mixture
      preparations for 48 h. The cell lysates were analyzed for protein content and
      collagen synthesis by direct binding enzyme immunoassay. The fibronectin of the
      cultured supernatant was measured by sandwich enzyme immunoassay. The results
      showed that CA, glycolic acid, vitamins A, E and C significantly stimulate
      collagen and fibronectin synthesis in the fibroblast. Addition of glycolic acid
      and vitamins to CA further increased the levels of collagen and fibronectin
      synthesis to 8.55 and 23.75 MUg/100 MUg, respectively. CA, glycolic acid,
      vitamins A, E, and C, and their mixtures demonstrated stimulatory effect on both
      extra-cellular matrix synthesis of collagen and fibronectin in in vitro studies
      on human foreskin fibroblasts, which is beneficial to skin care and therapeutic
      products formulation. 

PMID- 24577909
TI  - Low doses of colony-stimulating factors lead to resolution of neutropenia in
      cancer patients through increased levels of dihydrofolate reductase.
AB  - Low doses of granulocyte- colony stimulating factor (G-CSF) and granulocyte
      macrophage- colony stimulating factor (GM-CSF) have been shown to be beneficial
      in reducing duration of systemic antibiotic therapy and in-patient
      hospitalization by decreasing the period of neutropenia in cancer patients
      undergoing chemotherapy. Since the underlying mechanism is unclear, the aim of
      this study was to investigate whether the administration of G-CSF and GM-CSF in
      two different doses (low dose and standard dose) would result into resolution of
      neutropenia with concomitant increase in multiple forms of dihydrofolate
      reductase (DHFR, a pivotal enzyme in the pathway of de novo DNA synthesis).
      Thirty seven cancer patients (26 males and 11 females; age 14-73 years) having
      chemotherapy-induced neutropenia (absolute neutrophil counts <500/MUl) were
      treated with colony stimulating factor (CSF) in the following manner: 11 received
      GM-CSF (7 received a dose 250 MUg/m2 and 4 received a dose of 100 MUg/m(2)); 26
      received G-CSF (14 received a dose of 5 MUg/kg and 12 received a dose of 2.5
      MUg/kg). CSFs was given every day till the absolute neutrophil count was more
      than 1,000/MUl. Ten ml blood was collected from each patient and analyzed for
      total leukocyte count (TLC) and active DHFR and immunoreactive nonfunctional form
      of DHFR (IRE) in the cytoplasm of blood leukocytes by using methotrexate binding
      assay and enzyme-linked immunosorbent assay (ELISA). A significant increase
      (p<0.05) in concentrations of both active DHFR and IRE following stimulation with
      low as well as standard doses of CSFs was observed along with increase in the
      TLC. There was no significant difference in number of days to resolution of
      neutropenia at these two doses, indicating that even low doses of CSFs are
      clinically effective. Along with an increase in TLC, the levels of DHFR increased
      even at low doses of CSF suggesting that this might be one of the mechanisms for
      CSF-induced proliferation of leukocytes in neutropenic cancer patients.

PMID- 24577908
TI  - In vitro biological activity of decoction of Joshanda.
AB  - Joshanda is a polyherbal product, commonly practicing in inflammation of upper
      respiratory tract as tea. The present study was conducted to find out its
      antimicrobial, phytotoxic, leishmanicidal and cytotoxic activities. The decoction
      of the product showed profound activity against Gram positive tested pathogens
      especially S. aureus 36.5 mm zone of inhibition at 8.0 MUg/ml. However, it was
      inactive against C. albicans. Closed correlation was observed between two methods
      in terms of results. It had potent phytotoxic activity (75%). However, it was
      devoid of any activity leishmanicidal and cytotoxic activity. Phytochemical
      studies of Joshanda showed the presence of various pharmacologically active
      groups.

PMID- 24577910
TI  - Development and in vitro characterization of mebendazole delayed release tablet
      for colonic drug delivery.
AB  - The main objective behind this study was to formulate delayed release colon
      targeted tablet of Mebendazole by using different polymers. The precompressional
      parameters of powder blend were studied. The wet granulation method was used for
      the preparation of tablets. The tablets of all formulation were subjected for
      different physicochemical evaluation. The drug-excipient interaction study was
      carried out by using Fourier transforms Infrared spectroscopy (FTIR). The in
      vitro evaluation was carried out at different pH ranges (0.1M HCl, 6.8 and 7.4
      Phosphate buffer) for the prepared tablets. From the stability, Fourier transform
      infra-red spectroscopy studies Mebendazole tablet does not show any interaction
      between drug and polymer. The prepared tablets were complied all the
      physicochemical test as per official limit. The formulated (M3) batch shows
      better sustained release 99.89% over a period of 12 hours and the data was fitted
      into Korsemeyer-Peppas kinetic equation. The result indicates that Mebendazole
      colon targeted matrix tablet remain stable in the stomach and shows better
      release into the colon with the help of pH dependent synthetic polymers. 

PMID- 24577911
TI  - Spectrophotometric determination of citalopram hydrobromide in tablet dosage form
      using chloranil.
AB  - A fast, sensitive and extraction free spectrophotometric method for the
      quantitative determination of citalopram hydrobromide in pharmaceutical raw and
      tablet formulations has been proposed. The newly proposed method is based on the
      charge transfer reaction between citalopram as electron donor and chloranil as
      electron acceptor. The charge transfer complex of citalopram and chloranil shows
      lambda(max) at 550 nm in methanol. The experimental conditions such as reaction
      time, temperature, stoichiometry of the colored complex have been optimized. The
      developed method allows the determination of citalopram hydrobromide over a
      concentration range of 1-25 mg/ ml. The proposed method is used to determine the
      citalopram in tablet dosage forms. The results of proposed method are compared to
      the official USP method. The newly developed method is accurate, reproducible and
      easy to perform. It does not require stringent experimental conditions. No
      interference has been observed for excipients and additives in tablet
      formulations.

PMID- 24577912
TI  - Attenuation of erythrocytic acetyl cholinesterase by paracetamol and chloroquine:
      evidence in an in vitro study.
AB  - The present study deals with the erythrocytic acetylcholinesterase inhibitory
      activity of paracetamol and chloroquine in an in vitro protocol using Michaelis
      Menten parameters (Apparent Michaelis Constant (aKm) and Apparent Maximum
      Velocity (aVm). Paracetamol showed marked inhibition of the erythrocytic
      acetylcholinesterase. The inhibitory values for aKm and aVm were 65.6% 51.36%
      respectively, which reduced with respect to control and therefore, proposed an un
      competitive type of antagonism. When chloroquine was tested, it showed 45.14%
      inhibition for aKm which increased while 69.21% for aVm decreased with respect to
      control; proposed a mixed type of antagonism. In conclusion, the cholinergic
      intervention by paracetamol in this study suggested a new mechanism for its
      analgesic activity as acetylcholinesterase inhibitors have already shown both
      peripheral and central analgesic activity, while the cholinergic activation by
      chloroquine provided explanation for some of its side effects. 

PMID- 24577913
TI  - Anti-nociceptive and anti-inflammatory activities of extract of Anchomanes
      difformis in rats.
AB  - Anchomanes difformis is a tropical plant that has been used in folklore to treat
      diverse complications. The leaf extract of A. difformis was investigated for
      possible anti-nociceptive and anti-inflammatory effects in albino wistar rats. In
      these independent studies, two sets of twenty five rats were divided into five
      groups of five rats per group. Formalin induced pain in rats was used to
      investigate the anti-nociceptive effect of the extract. The extract was
      administered orally in the treated groups at doses 200, 400, 800 and 1600 mg/kg
      with aspirin serving as the positive drug control while the normal control group
      was not given any extract but water. Studies were also carried out on the egg
      albumin induced anti-inflammatory activity in rats by inducing oedema on the left
      hind paw. The result showed a significant inhibition (p<0.05) on the later phase
      (800mg/kg) of formalin pain induction in rats; similarly, a significant (p<0.05)
      anti-inflammatory activity was observed at 60, 90 and 120 minutes. The study thus
      validates the ethnomedicinal usage of A. difformis in the treatment of pain and
      inflammation. 

PMID- 24577914
TI  - Synthesis, characterization and enzyme inhibition study of O-substituted
      derivatives of chlorinated coumarin.
AB  - Coumarins have much importance in dyes, drugs, perfumes and pesticides. In the
      demonstrated research work, a benignant series of chlorinated coumarins was
      synthesized and screened against different enzymes. First, 6-Chloro-7-hydroxy-4
      methyl-2H-chromen-2-one (3) was geared up by the reaction of 4-chlororesorcinol
      (1) and ethyl acetoacetate (2) in the presence of concentrated H(2)SO(4). Second,
      various O-substituted derivatives of chlorinated coumarins, 5a-j, were set up by
      pairing different alkyl/aralkyl halides, 4a-j, with 3 in the presence of NaH in
      DMF as solvent. The structures of all the synthesized compounds were clarified
      through spectral analysis using EI-MS, IR and (1)H-NMR. The different enzymes
      used for the evaluation of bioactivity of all the synthesized compounds were
      acetyl cholinesterase (AChE), butyryl cholinesterase (BChE) and lipoxygenase
      (LOX). The most proficient activity was shown against both cholinesterase
      enzymes.

PMID- 24577915
TI  - In vitro antioxidant potential and free radical scavenging activity of various
      extracts of pollen of Typha domigensis Pers.
AB  - Antioxidant potential of the pollen of Typha domigensis Pers. using Ferric
      Reducing ower, Metal Chelating Activity and Trolox Equivalent Antioxidant
      Capacity (TEAC) assays has been carried out in the current research work. The
      antioxidant components were initially extracted from the pollen in methanol and
      were further fractionated in solvents of different polarity such as n-Hexane,
      Chloroform, Ethyl Acetate and Water. Methanol extract which was found to have
      high reducing power, total phenolic contents with high metal chelating activity,
      has considerable prospective to utilize as a natural antioxidant and be capable
      to link with the total phenolic contents of plant. 

PMID- 24577916
TI  - Activity directed investigation on anti-inflammatory fractions and compounds from
      flowers of Trollius chinensis.
AB  - The flower of Trollius chinensis Bunge is used as an anti-inflammatory drug to
      treat upper respiratory tract infection, pharyngitis, tonsillitis, and
      bronchitis. In order to identify the active components, the activity-screen
      directed compound isolation was carried out, leading to the identification of the
      major active fraction and 4 compounds thereof. As a result, flavonoids and
      phenolics were demonstrated to be the major anti-inflammatory components. 

PMID- 24577918
TI  - Cellular and genomic toxicity produced by UV light in Chinese hamster ovary
      cells.
AB  - UVB and UVC toxicity was detected in Chinese Hamster Ovary (CHO) cell lines AA8,
      UV5 and XEM2 (a V79-derived cell line expressing rat P450 1A1). Unlike FICZ-HPLC
      assay that showed induction of CYP1A1 enzyme activity after 20 minutes and 2 hour
      UVC exposure, the EROD assay showed no difference in cytochrome P450 1A1 (CYP1A1)
      activity after exposure to different doses of UVB and UVC light. Different
      cytotoxic and mutagenic effect of photo lesions induced by UVC and UVB light was
      investigated with the DRAG and HPRT assays, comparing the wild type cell line AA8
      and the Nucleotide Excision Repair (NER) deficient cell line UV5. DRAG assay
      showed a significant difference in UV induced cytotoxicity between UVC and UVB
      reflecting the larger energy and toxic effect of UVC along with significant
      difference in UV induced toxicity between AA8 and UV5 cell lines. This was
      further validated through the HPRT assay, which also showed a significant
      difference in UVC (5 J/m(2)) induced mutagenic effect between these cell lines.
      In addition, HPRT assay showed the mutagenic effect of photosensitizer,
      acetophenone. These results show that UVB and UVC generate serious damage through
      photo products on DNA, and might induce the metabolic activity of CYP1A1.

PMID- 24577917
TI  - Anxiolytic effect of herbal medicine, Khamira Gaozaban Ambri Jadwar Ood Salib
      Wala (KGJ) in experimental rat models.
AB  - Anxiety and depression leads to a number of morbid states. Search of new agents
      which are low-priced and safe alternative is necessary. Khamira Gaozaban Ambri
      Jadwar Ood Salib wala (KGJ), is a product of Hamdard Laboratories (Waqf)
      Pakistan. They claim that it is anxiolytic, anti-convulsant and nervine tonic.
      However this claim is not scientifically proven. Some components are proved to be
      anxiolytic but combination may alter the individual properties of drugs.
      Therefore we designed present study to prove these properties of KGJ
      scientifically. Thirty male Sprague Dawley rats were divided into five groups of
      six animals in each group. The groups were saline group, control group (receiving
      Diazepam I mg/kg) and three test groups receiving 86, 170 and 360 mg/kg doses of
      Khamira orally. Assessments of different doses of KGJ in comparison to diazepam
      were carried out on anxiety paradigms namely "Elevated Plus Maze", "Light And
      Dark Activity Box" and "Open Field" paradigms. KGJ produced anxiolytic effects in
      all the behavioral methods, which were not significantly different from the
      effects produced by diazepam. Basal levels of corticosterone not altered by
      diazepam were decreased by 86 mg/kg dose of KGJ. Same dose of KGJ also decreased
      blood glucose levels. In conclusion, these results suggest anxiolytic potential
      of KGJ with non-sedative property. 

PMID- 24577919
TI  - Effect of dichloromethane fraction of Areca catechu nut on monoamines associated
      behaviors and tyramine pressor sensitivity in rodents.
AB  - The current study was aimed at investigating the effect of Areca catechu nut
      dichloromethane fraction (7 mg/kg) on monoamines (serotonin and dopamine)
      modulation (5-hydroxytryptophan-induced tremors and phenylethylamine-induced
      stereotypes) and its interaction with tyramine (cheese effect). The
      dichloromethane fraction caused pronounced increase in 5-HTP-induced tremors
      (50%) with negligible PEA-induced stereotypes (20%). Additionally, it did not
      produce a significant increase in the tyramine pressor effects. These results
      suggest that the dichloromethane fraction of A. catechu nut primarily elevates
      serotonin levels (probably via monoamine oxidase A inhibition) and does not
      induce cheese effect. 

PMID- 24577920
TI  - Acute toxicity and antispasmodic activities of Achillea wilhelmsii C. Koch.
AB  - Since Achillea wilhelmsii is used as antispasmodic in traditional medicine, we
      conducted our current work to investigate its rationale on scientific grounds.
      Acute toxicity studies of crude methanol extract of Achillea wilhelmsii (Aw.
      CMeOH) is also performed. Effect of Aw. CMeOH and its fractions were tested on
      isolated sections of rabbits' jejunum at test concentrations 0.01, 0.03, 1.0,
      3.0, 5.0 and 10mg/ml. The test extracts, in similar concentrations, were also
      tested on KCl-induced contractions. Calcium chloride curves were constructed for
      those fractions which relaxed KCl induced contractions in the absence and
      presence of the test samples to investigate its possible mode of action through
      calcium channels. Aw. CMeOH tested positive for flavonoids, saponins, tannins,
      glycosides, terpenoids, sterols, phenols, carbohydrates and proteins. LD(50) for
      acute toxicity studies is 2707+/-12.6 mg/kg. Mean EC(50) values for Aw. CMeOH on
      spontaneous and KCl-induced contractions are 3.41+/-0.18 (2.56-3.8, n=6) and
      0.68+/-0.05 (0.6-0.85, n=6) mg/ml, respectively. Respective EC(50) values for n
      hexane fraction on spontaneous and KCl-induced contractions are 3.06+/-0.08 (2.8
      3.3, n=6) and 1.68+/-0.8 (1.4-1.9, n=6) mg/ml, respectively. Corresponding EC(50)
      (mg/ml) values for chloroformic, ethylacetate and aqueous fractions of Achillea
      wilhelmsii on spontaneous rabbits' jejunum preparations are 4.8+/-0.2 (4.41-5.63,
      n=6), 5.07+/-0.15 (4.7-5.58, n=6) and 5.2+/-0.13 (4.91-5.64, n=4), respectively.
      Constructing calcium chloride curves, in the presence of 0.1 mg/ml of Aw. CMeOH,
      mean EC(50) value (log molar [Ca(++)]) is-1.98+/-0.03 (-1.89-2.05, n=6) vs.
      control EC(50) (log molar [Ca(++)])-2.41+/-0.02 (-2.32-2.44, n=6). Mean EC(50)
      value (log molar [Ca(++)]) for 0.3 mg/ml n-hexane fraction is-1.76+/-0.05 (-1.70 
      1.93, n=6) vs. control EC(50) (log molar [Ca(++)]) value-2.18+/-0.07 (-2.0-2.46,
      n=6). While in the presence of chloroformic fraction (3 mg/ml), mean EC(50) (log
      molar [Ca(++)]) value is -2.4+/-0.1 (-2.78 -2.9, n=6) vs. control EC(50) (log
      molar [Ca(++)]) value-2.70+/-0.05 (-2.5-2.8, n=6). Mean EC(50) value (log molar
      [Ca(++)]) for ethyl acetate fraction (1 mg/ml) is-1.94+/-0.07 (-1.75-2.05, n=6)
      vs. control EC(50) (log molar [Ca(++)]) value-2.69+/-0.04 (-2.57-2.79, n=6). Mean
      EC(50) (log molar [Ca(++)]) value for residual aqueous fraction (3 mg/ml) is
      1.8+/-0.3 (-1.71-1.84, n=6) vs. control EC(50) (log molar [Ca(++)]) -2.6+/-0.04 (
      2.59-2.76, n=6). Whereas, the verapamil (0.1uM) EC(50) value (log molar [Ca(++)])
      is-1.7+/-0.1 (-1.6-1.8, n=6) vs. control EC(50) value (log molar [Ca(++)])- 2.4+/
      0.09 (-2.3-2.47, n=6). The present research work confirms that the intestinal
      relaxation effect of Achillea wilhelmsii is supporting its traditional use as
      antispasmodic. The plant species can be a source for calcium antagonist(s), which
      can preferably be isolated from n-hexane fraction. 

PMID- 24577921
TI  - Clinical efficacy of herbal coded formulation ocucure for the improvement of
      presbyopia: a randomized comparative clinical trial.
AB  - A progressively diminishing capacity of eye to visualize for close proximity
      increasing by age is known as presbyopia which is usually resulted due to loss of
      elasticity of crystalline lens. A clinical trial was conducted to evaluate the
      efficacy of coded herbal formulation "ocucure" (Test drug) for the treatment of
      presbyopia comparing with leutivit (Placebo). One hundred and eleven patients
      suffering from presbyopia from both groups (Males: 63, mean age: 34+/-14 and
      females: 48, mean age: 33+/-13 year, range: 20-60) were enrolled in the trial and
      divided in to two groups according to treatment regimens. Ocucure (Test drug)
      500mg two tablets and leutivit (Placebo) 250mg tablets twice daily were
      prescribed for 6-8 weeks. Presbyopia was improved in 17 patients (28.81%) out of
      59 patients by the use of ocucure (Test drug), and in 6 patients (11.53%) out of
      52 by the use of leutivit (Control drug). Furthermore, there was a significant
      improvement in presbyopic associated clinical features as compared to leutivit.
      It is concluded that ocucure possesses a therapeutic value for the improvement of
      presbyopia and its associated symptoms as compared to leutivit. 

PMID- 24577922
TI  - Bone Marrow Stromal Cell (BMSC) and skeletal aging: role of telomerase enzyme.
AB  - Telomere shortening and telomerase deficiency have been linked with several age
      related degenerative diseases. Moreover, degenerative changes in various
      tissues/organs have been attributed to derangement of stem cell functions causing
      regenerative tragedy. Bone marrow stromal cells (BMSCs) are considered the ideal
      candidates for regenerative approaches owing to their beneficial effects in
      numerous clinical applications. Thus, the effect of telomerase deficiency in
      perpetrating age related changes in BMSC functions during in vitro culture; their
      morphology, proliferation and differentiation, that can be extrapolated and
      reasoned for skeletal aging is conversed in this review. Besides, information
      regarding pertinent molecular and biochemical markers that can be employed to
      examine the earliest events, during the course of BMSC aging, is also provided.
      Additionally, impact of telomerase deficiency in enacting skeletal aging
      phenotype and its associated microenvironment is also discussed. In the end,
      further studies, using tissue specific models of telomerase deficiency, are
      recommended as a future research strategy to advance our understanding of tissue
      specific telomerase regulation. 

PMID- 24577924
TI  - Exploiting the interaction of polymethacrylates with iron oxide for the
      enhancement of mucoadhesive strength.
AB  - The present investigation was aimed at preparation of polymethacrylate(s)- iron
      oxide conjugates and to evaluate mucoadhesive performance using texture analyzer.
      Eudragit RL-iron oxide or Eudragit RS-iron oxide conjugate granules were prepared
      by solvent evaporation technique. The mucoadhesive strength of pure Eudragit RL
      and RS was found to be 11.25+/-2.02 and 7.78+/-0.92 g respectively, whereas the
      same was found to be 36.42+/-4.01 and 24.32+/-4.44 for the iron oxide conjugates
      of Eudragit RL and RS respectively. Hence, mucoadhesive strength of
      polymethacrylates was found to be enhanced by this technique while, retaining
      their pH resistant property. A correlation (p>0.05) of 0.97 between mucoadhesive
      strength and zeta potential indicated conjugation of iron oxide contributed
      positive surface charge that causes enhancement of mucoadhesion. Further, the ATR
      FTIR spectral analysis as well as DSC analysis supported existence of ionic
      interactions between conjugates (Eudragit RS or RL with iron oxide) and the
      tissue surface. Hence, the findings point out toward the expected potential use
      and application of Eudragit RL-iron oxide conjugate in mucoadhesive drug delivery
      systems, gastro retentive drug delivery systems, etc. 

PMID- 24577923
TI  - Phytochemical and pharmacological studies on methanolic seeds' extract of
      Dolichos biflorus.
AB  - The Dolichos biflorus is a well known medicinal plant in folklore for its
      medicinal properties. In herbal medicine the seeds of it are mainly used as
      tonic, astringent, diuretic, and are also recommended in asthma, bronchitis,
      urinary discharges, hiccoughs, ozoena, heart trouble and other diseases of brain.
      The main purpose of this study is to explore and to provide experimental data on
      the traditional use of plant Dolichos biflorus. For this purpose we investigated
      the plant seed extract phytochemically and pharmacologically. Phytochemical
      analysis was performed on extract and powder form of the drug. Procedure use for
      evaluation were Identification of chemical constituent by color reaction,
      Fluorescence analysis of powder drug, pH (in powder and extract forms), loss on
      drying, Thin layer chromatography, Infrared spectroscopy, acid and saponification
      values. In pharmacological studies (diuretic, analgesic and anti-inflammatory
      activities) were tested on the extract of plant seed. The tests were carried out
      over albino mice taking different concentration of seed extract. Seeds extract of
      Dolichos biflorus has exhibited mild analgesic activity, the results were (84.6+/
      6.68) at dose 300mg/kg and (92.2+/-6.81) at dose 500mg/kg which were not much
      significant as compared to reference drug Aspirin (300mg/kg) having result
      (36.4+/-2.27). While seed extract of Dolichos biflorus exhibited remarkable
      diuretic activity, the values at 300 mg/kg was (1.33+/-0.13) and at 500 mg/kg
      were (2.66+/-0.31) which are highly significant as compared to drug Lasix (20mg
      /kg) having result (2.38+/-0.23). Anti-inflammatory effects of crude extract of
      Dolichos biflorus obtained at 0.06mg/kg and 01mg/kg were (26.6+/-2.96) and (36+/
      1.67) respectively. While the value for aspirin as standard drug (300mg/kg) were
      (17.44+/-1.59).This study provides a platform for further investigation for the
      isolation of active principles responsible for biological activity. 

PMID- 24577925
TI  - Cytotoxic and antimicrobial activities of Emex spinosa (L.) Campd. extract.
AB  - The current research was designed to evaluate the phytochemical contents,
      cytotoxic and antimicrobial activity of Emex spinosa extracts. The different
      plant extracts and Aloe-emodin glucoside were screened using the colorimetric MTT
      method (3-(4,5-dimethylthiazo-2-yl)-2,5-diphenyl- tetrazolium bromide) assay to
      test their in vitro cytotoxic activity against HepG2, MCF-7, Caco-2 and HCT. The
      clinically used anticancer drug doxorubicin was used as standard for comparative
      purposes. Anthraquinones (Aloe-emodin-O-glucoside, Emodin and nataloin (1, 2, 8
      trihydroxy, 6-methyl, 10-anthrone-C-glucoside) together with beta-sistosterol and
      beta-sitisterol-O-beta-D-glucoside were isolated from Emex spinosa. Aloe-emodin
      glucoside together with four fractions from this plant were evaluated for their
      anticancer and antimicrobial activities. Aloe-emodin glucoside showed anticancer
      activity against HCT, HepG-2, MCF-7 and Caco-2 cell lines. The total ethanol
      extract of E. spinosa and diethyl ether, chloroform, ethyl acetate and butanol
      fractions shown antibacterial activity against Staphylococcus aureus,
      Streptococcus pyogenes and Bacillus subtilis. 

PMID- 24577926
TI  - Association of endothelial nitric oxide synthase (eNOS) gene polymorphism (Glu
      298 Asp) with coronary artery disease in subjects from Multan, Pakistan.
AB  - Acute Coronary Syndrome (ACS) is the most common disease and cause of mortality
      in both genders across the world and certain risk factors i.e. age, gender,
      smoking, diabetes, hypertension, drugs usage, weight etc are known to be
      associated with the disease. The aim of this study was to find if there is any
      correlation exists between ACS and hereditary genetic defect in endothelial
      nitric oxide synthase (ecNOS) gene as eNOS generates Nitric oxide in blood
      vessels and regulates the vascular tone hence directly affecting the
      cardiovascular function. Single nucleotide polymorphism (SNP) (Glu 298 Asp) in
      ecNOS was determined in 280 subjects, from Southern Punjab (in Pakistan)
      population, including (160 ACS patients and 120 healthy controls) by PCR-RFLP
      method and genotype was correlated with various risk factors as well as with
      serum cholesterol and triglyceride levels. Our results indicated that the
      genotype Glu 298 Asp was not associated with ACS but when various studied
      parameters were compared among patients suffering from various forms of ACS and
      their healthy controls, it was observed that age (45-55 years) (P = 0.05), gender
      (male) (P < 0.001), education (P<0.001), family history (P=0.03), hypertension
      (P<0.001), diabetes (P<0.01) and smoking habit (P = 0.03) were the significantly
      different parameters among them and may be associated with the incidence of
      cardiovascular disease. Cholesterol (161.5+/-79 mg/dL) level was found to be
      higher in patients (P = 0.04) than controls while triglyceride remained
      unaffected (P = 0.87) in both groups. 

PMID- 24577927
TI  - Evaluation of anti-inflammatory activity of selected medicinal plants of Khyber
      Pakhtunkhwa, Pakistan.
AB  - In present study, the anti-inflammatory potential of three medicinal plants,
      Xanthium strumarium, Achyranthes aspera and Duchesnea indica were evaluated,
      using both in vitro and in vivo assays. Carrageenan induced hind paw edema model
      was used to carry out the in vivo anti-inflammatory activity, while for in vitro
      screening lipoxygenase inhibition assay was used. Crude extract of all the
      selected plants depicted significant (plt;0.001) anti-inflammatory activity, at
      late phase of inflammation. Achyranthes aspera also showed considerable anti
      inflammatory activity (47%) at relatively lower concentration (200 mg/ml), at the
      initial phase of inflammation. Similarly the ethyl acetate fraction of all the
      selected plants showed significant lipoxygenase inhibition activity when compared
      with the standard drug (Baicalein). The results obtained from both in vitro and
      in vivo anti-inflammatory activity suggest that the ethyl acetate fraction of the
      crude extract of all the selected plants can be used for the isolation of new
      lead compounds with better anti-inflammatory activity. 

PMID- 24577928
TI  - Development and in vitro evaluation of a transdermal hydrogel patch for ferulic
      acid.
AB  - Current work aimed to develop and evaluate a transdermal delivery system of
      hydrogel patch for ferulic acid to treat skin damage induced by UV radiation.
      VISCOMATE(TM) NP700, dihydroxy aluminium aminoacetate, glycerine, tartaric acid
      were used in combination in different ratios to design the hydrogel patch. In
      vitro release rate was selected as an index to optimize the formulation. The
      formulated hydrogel patch was evaluated by several parameters like tacking
      strength, cohesive strength, peeling strength, residuals after peeling and drug
      content determination. The in vitro penetration was determined by Franz diffusion
      technology with hairless mouse skin as permeability media. Different kinetics
      models were employed to simulate the release and penetrate patterns of ferulic
      acid from patches in order to investigate the drug transport mechanism. The
      residual drugs in the patch and skin were determined after the penetration
      experiment. The optimized preparation was dihydroxy aluminium aminoacetate:
      NP700: glycerine: ferulic acid as a ratio of 0.02:0.4:1.5:1.25:0.25. The
      cumulative percentage of release was 60.4465+/-1.7679% for 24h, which results
      from a combination of diffusion effect and polymer erosion effect. For the
      barrier of stratum corneum, the cumulative penetrate rate was only 1.3156+/
      0.3588% and the release mechanism turn out to be the effect of erosion of polymer
      surface. The residual drugs in the patch were 97.5949+/-1.4932%. The in vitro
      data revealed that it was easy for ferulic acid to release from the paste while
      difficult to permeate through the skin barrier, which resulted in most of drugs
      residued in the paste. Hence, further experiments will be necessary for finding
      the penetration enhancer in ferulic acid transdermal delivery. 

PMID- 24577929
TI  - Effect of Carthamus tinctorius (Safflower) on fasting blood glucose and insulin
      levels in alloxan induced diabetic rabbits.
AB  - Diabetes mellitus is a major threat to present and future generations. The role
      of herbal medication has emerged as a safe alternative to currently available
      medication due to its decreased potential to produce side effects, hence effect
      of Carthamus tinctorius was observed on fasting blood glucose and insulin levels
      in alloxan induced diabetic rabbits. Thirty five healthy male rabbits were
      divided into 5 groups with 7 rabbits in each (Normal control, diabetic control,
      diabetic treated with glibenclamide, diabetic treated with Carthamus tinctorius
      extract at doses of 200 and 300mg/kg of body weight). Drug and extract were given
      orally for 30 days and the values for blood glucose levels were observed after
      15(th) and 30(th) day of treatment by using standard reagent kits provided by
      Human Germany. While insulin levels were checked at the end of the study by using
      Architect i1000 by Abbott Diagnostics USA. Animals were also observed for any
      gross toxicity during the study. Results revealed that Carthamus tinctorius has
      significant hypoglycemic effect at 200mg/kg and 300mg/kg doses as compared to
      diabetic control group. Insulin levels were significantly increased in
      Glibenclamide treated as well as Carthamus tinctorius treated groups as compared
      to diabetic control.

PMID- 24577930
TI  - Report: prevalence of shigellosis in three different areas of Karachi.
AB  - Shigellosis is communicated when the pathogen is swallowed down through the
      factors like stool or polluted hands with dust. Inappropriate hygienic conditions
      may reach such clinical manifestations. Shigellosis is frequently originated in
      crowded places and where hygienic conditions are insufficient and sanitation is
      poor. Infections easily transmissible from person to person like family members
      or infected playmates. The disease can easily transmit through infected food
      handlers with inappropriate hygienic conditions, crops nurturing in contaminated
      water with sewage line system, swimming in contaminated pool water. Similarly
      houseflies can also form an important vector for its transmission. In this study,
      Ecological factors were also the causative indicators for the disease. The issue
      was the water contamination of the different areas of Karachi mainly the Pehlwan
      Goth, Safora Goth. Then another area we focused was Patel Para in which
      Salmonella species were present. Other indicator was the individual-to-individual
      transfer that was common in Safora Goth. 

PMID- 24577931
TI  - Report: pharmacokinetic and drug interaction studies of pefloxacin with
      paracetamol (NNAID) in healthy volunteers in Pakistan.
AB  - In the present study, the pharmacokinetic and drug interaction evaluation of two
      drugs pefloxacin and paracetamol was carried out by a single-dose, two-treatment
      and two-sequence crossover design. Total fifteen healthy volunteers participated
      out of which ten completed the study. All were male volunteers, aged 22.36 years
      (means), with a mean weight of 76.45+/-12.05 Kg. The washout period between
      treatments was 5 week. Initially the method utilized for quantitative analysis of
      the drug was developed which was further validated. The study involved plasma
      protein precipitation with ethyl acetate and detection was done at 275nm. The
      retention time for pefloxacin 18+/-1 min and paracetamol were approximately 6+/-1
      min, respectively. The calibration curve for pefloxacin was linear in the
      concentration range of 0.125-12.0mg/ml with r(2)=0.9987 in plasma. Standard
      concentration solution was maintained on the same temperature as that of
      volunteer's samples to optimize the periods for the determination of drug
      concentration in the plasma samples. Blood samples were collected from volunteers
      at different time intervals. The pharmacokinetics and drug interaction studies
      were anticipated by plotting concentration versus time-profiles. The value of
      AUC0-infinity in control was 67.355+/-3.174MUg.h/ml, in treatment 61.242+/
      3.868MUg.h/ml along with relative bioavailability =91.395+/-4.864. Under the
      control and treatment condition the mean maximum plasma concentrations were found
      to be 4.679+/-0.248 MUg/ml and 4.6595+/-0.266 MUg/ml respectively. The average
      T(max) for plasma concentrations was 1.819+/-0.1743hr and 1.605 +/-0.1134hr
      respectively. The biological half-lives in the two phases of studies were found
      to be 7.953+/-0.33hr in control and 7.7257+/-0.355hr in treatment. No significant
      effect were observed on the bioavailability and pharmacokinetics of pefloxacin by
      the concomitant administration with paracetamol, however very minor effect were
      observed that might be related with inter-individual variation in human
      volunteers. This pharmacokinetic studies also indicated that the level of drug
      (Cmax) do not differ from previous studies in different races.

PMID- 24577932
TI  - Review: an exposition of medicinal preponderance of Moringa oleifera (Lank.).
AB  - Medicinal plants are believed to be a precious natural reservoir as they are
      assumed to have paranormal effects for the mankind. Moringa oleifera grows
      throughout most of the tropics and has numerous industrial and medicinal uses.
      This review acquaints with the consequence of fera (Moringaceae), a fast growing
      medicinal plant wide spread in tropical regions with height ranging from 5-10m.
      It has an enormous nutritional worth due to existence of vitamins and proteins.
      It is subsisted with many constituents. Its oil consists of oleic, tocopherols,
      stearic, palmitic, behenic and arachidic acid. Flavanoids and phenolics such as
      gallic acid, chlorogenic acid, ferulic acid, kaempferol, ellagic acid, quercetin
      and vanillin are present by means of leaf extract, being richest in phenolics and
      subsequent fruit and seed extract respectively, that are accountable for
      antioxidant activity of plant. Seeds have been pragmatic with active components
      as novel O-ethyl-4- (alpha -L-rhamnosyloxy) benzyl carbamate together with seven
      known compounds, 4 (alpha -L-rhamnosyloxy)-benzyl isothiocyanate, niazimicin,
      niazirin, beta-sitosterol, glycerol-1- (9 -octadecanoate), 3 -O- 6 -O-oleoyl-
      beta -D-glucopyranosyl-b-sitosterol, and beta - sitosterol- 3-X-O -beta -D
      glucopyranoside , that have been discerned to inhibit EBV-EA (Epstein- Barr virus
      early antigen), that is persuaded by the cancer promoter. M. oleifera leaves,
      gums, roots, flowers as well as kernels have been unanimously utilized for
      managing tissue tenderness, cardiovascular and liver maladies, normalize blood
      glucose and cholesterol. It has also profound antimicrobial, hypoglycemic and
      anti-tubercular activities. 

PMID- 24577933
TI  - Review: probiotics and their beneficial effects against various diseases.
AB  - Joint FAO/WHO expert's consultation report defines probiotics as: Live
      microorganisms which when administered in adequate amounts confer a health
      benefit on the host. Most commonly used probiotics are Lactic acid bacteria (LAB)
      and bifidobacteria. There are other examples of species used as probiotics
      (certain yeasts and bacilli). Probiotic supplements are popular now a days. From
      the beginning of 2000, research on probiotics has increased remarkably.
      Probiotics are now day's widely studied for their beneficial effects in treatment
      of many prevailing diseases. Here we reviewed the beneficiary effects of
      probiotics in some diseases. 

PMID- 24577935
TI  - Clinical and serologic correlates of anti-PM/Scl antibodies in systemic
      sclerosis: a multicenter study of 763 patients.
AB  - OBJECTIVE: Anti-PM/Scl autoantibodies are found in polymyositis, dermatomyositis,
      systemic sclerosis (SSc), and systemic autoimmune disease overlap syndromes. PM
      1alpha is a major epitope of the PM/Scl complex, and antibodies against PM-1alpha
      can be detected using a validated enzyme-linked immunosorbent assay (ELISA). This
      study was undertaken to determine the prevalence and identify the clinical
      correlates of anti-PM-1alpha antibodies in a large cohort of patients with SSc.
      METHODS: Serum samples were obtained from 763 patients with SSc enrolled in a
      multicenter Canadian cohort. The sera were analyzed by ELISA for the presence of
      antibodies against PM-1alpha. Associations between the presence of anti-PM-1alpha
      antibodies and demographic, clinical, and other serologic manifestations of SSc
      were investigated. RESULTS: Anti-PM-1alpha antibodies were present in 55 patients
      with SSc (7.2%), of whom almost 50% (26 of 55; 3.4% of the overall cohort) had no
      other SSc-specific antibodies, namely anticentromere, anti-topoisomerase I, and
      anti-RNA polymerase III. Features positively associated with the presence of anti
      PM-1alpha antibodies included younger age at disease onset, skeletal muscle
      involvement, calcinosis, inflammatory arthritis, and overlap disease.
      Interstitial lung disease was less frequent and there were fewer gastrointestinal
      symptoms present in patients with anti-PM-1alpha antibodies compared to patients
      without these antibodies. CONCLUSION: Anti-PM-1alpha antibodies are relatively
      common in SSc and are associated with a distinct clinical phenotype, consistent
      with that described in association with other anti-PM/Scl autoantibodies.
      Although anti-PM-1alpha antibodies are not exclusive of other SSc-specific
      antibodies, they can be present in the absence thereof. Thus, anti-PM-1alpha
      antibodies may have considerable diagnostic and prognostic relevance in SSc.

PMID- 24577934
TI  - Risk factors for anxiety disorders: common and specific effects in a national
      sample.
AB  - BACKGROUND: Anxiety disorders and major depressive disorder (MDD) often co-occur
      and share a broad range of risk factors. The goal of this study was to examine
      whether the co-occurrence of anxiety disorders and MDD could be explained by an
      underlying latent factor and whether the risk factors exert their effect
      exclusively through this factor, directly on each disorder, or through a
      combination of effects at both levels. METHODS: Data were drawn from a large,
      nationally representative sample. Confirmatory factor analysis was used to
      identify the latent structure of anxiety disorders. A multiple indicators
      multiple causes (MIMIC) approach was used to assess the common and specific
      effects of risk factors for anxiety disorders. RESULTS: A one-factor model
      provided a good fit to the co-occurrence of anxiety disorders. Low self-esteem,
      family history of depression, female sex, childhood sexual abuse, White race,
      years of education, number of traumatic experiences, and disturbed family
      environment increased the risk of anxiety disorders and MDD through their effect
      on the latent factor. There were also several direct effects of the covariates on
      the disorders, indicating that the effect of the covariates differed across
      disorders. CONCLUSIONS: Risk for anxiety disorders and MDD appears to be mediated
      partially by a latent variable underlying anxiety disorders and MDD, and
      partially by disorder-specific effects. These findings may contribute to account
      for the high rates of comorbidity among disorders, identify commonalities in the
      etiologies of these disorders, and provide clues for the development of unified
      preventive interventions.

PMID- 24577937
TI  - Sitting posture makes a difference-embodiment effects on depressive memory bias.
AB  - Basic research has shown that the motoric system (i.e., motor actions or stable
      postures) can strongly affect emotional processes. The present study sought to
      investigate the effects of sitting posture on the tendency of depressed
      individuals to recall a higher proportion of negative self-referent material.
      Thirty currently depressed inpatients either sat in a slumped (depressed) or in
      an upright (non-depressed) posture while imagining a visual scene of themselves
      in connection with positive or depression related words presented to them on a
      computer screen. An incidental recall test of these words was conducted after a
      distraction task. Results of a mixed ANOVA showed a significant posture x word
      type interaction, with upright-sitting patients showing unbiased recall of
      positive and negative words but slumped patients showing recall biased towards
      more negative words. The findings indicate that relatively minor changes in the
      motoric system can affect one of the best-documented cognitive biases in
      depression. Practical implications of the findings are discussed.

PMID- 24577936
TI  - Treatment complications and survival in advanced laryngeal cancer: a population
      based analysis.
AB  - OBJECTIVES/HYPOTHESIS: Primary curative treatment of advanced laryngeal cancer
      may include surgery or chemoradiation, although recommendations vary and both are
      associated with complications. We evaluated predictors and trends in the use of
      these modalities and compared rates of complications and overall survival in a
      population-based cohort of older adults. STUDY DESIGN: Retrospective population
      based cohort study. METHODS: Using Surveillance Epidemiology and End Results
      (SEER) cancer registry data linked with Medicare claims, we identified patients
      over 65 with advanced laryngeal cancer diagnosed 1999 to 2007 who had total
      laryngectomy (TL) or chemoradiation (CTRT) within 6 months following diagnosis.
      We identified complications and estimated the impact of treatment on overall
      survival, using propensity score methods. RESULTS: The proportion of patients
      receiving TL declined from 74% in 1999 to 26% in 2007 (P < 0.0001). Almost 20% of
      the CTRT patients had a tracheostomy following treatment, and 57% had a feeding
      tube. TL was associated with an 18% lower risk of death, adjusting for patient
      and disease characteristics. The benefit of TL was greatest in patients with the
      highest propensity to receive surgery. CONCLUSION: TL remains an important
      treatment option in well selected older patients. However, treatment selection is
      complex; and factors such as functional status, patient preference, surgeon
      expertise, and post-treatment support services should play a role in treatment
      decisions. LEVEL OF EVIDENCE: 2b. Laryngoscope, 124:2707-2713, 2014.

PMID- 24577938
TI  - International quality assurance project in colorectal cancer-unifying diagnostic
      and histopathological evaluation.
AB  - PURPOSE: Several European countries are undertaking quality control projects in
      colorectal cancer. These efforts have led to improvements in survival, but a
      comparison between different projects reveals questionable results. The aim of
      this study is the presentation of results from hospitals in three different
      European countries participating in the International Quality Assurance in
      Colorectal Cancer (IQACC) project. METHODS: For this publication, patients with
      cancer of the colon or rectum treated in 2009 and 2010 and recorded in the IQACC
      (Germany, Poland and Italy) were analysed. The comparison included number of
      patients, age, preoperative diagnostics (CT of the abdomen and thorax, MRI,
      colonoscopy, ultrasound, tumour markers), surgical approach, metastasis, height
      of rectal cancer and histopathological examination of a specimen (T stage, N
      stage and MERCURY classification for rectum resection). For short-term outcomes,
      general complications, wound dehiscence, tumour-free status at discharge,
      anastomotic leakage and in-hospital mortality were analysed. RESULTS: A total of
      12,691 patients (6,756 with colon cancer, 5,935 with rectal cancer) were included
      in the analysis. Preoperative diagnostics differed significantly between
      countries. For pT and pN stages, several quality differences could be
      demonstrated, including missing stages (colon cancer: pT 5.7-12.5 %, pN 2.5-11.0
      %; rectal cancer: pT 1.1-5.6 %, pN 1.1-15.5 %). The most relevant differences for
      short-term outcomes in colon cancer were found in general complications (4.2-22.8
      %) and tumour-free status at discharge (74.5-91.7 %). In-hospital deaths ranged
      between 2.5 and 4.3 % and did not show significant differences. For rectal
      cancer, the country with the highest percentage of tumours localised less than 4
      cm from the anal verge (16.0 %) showed the lowest frequency of amputation (8.5
      %). Outcome differences were found for general complications (3.2-18.8 %),
      anastomotic leakage (0-4.3 %) and tumour-free status at discharge (72.9-87.6 %).
      In-hospital deaths ranged between 1.1 and 3.2 %. CONCLUSION: This study
      demonstrates the feasibility of an international quality assurance project in
      colorectal cancer. This concept ensures data analysis based on a comparable data
      input. Differences in preoperative diagnostics, completeness of histopathological
      evaluation and short-term outcomes for Germany, Poland and Italy might result
      from disparities in socioeconomic factors and implementation of existing
      guidelines. Further activities are necessary to warrant the use of common
      standards in outcome control.

PMID- 24577939
TI  - Detection of monoclonal IGH rearrangements in circulating cells from healthy
      first-degree relatives of patients with multiple myeloma.
AB  - Multiple myeloma (MM) is characterized by abnormal proliferation of clonal plasma
      cells or monoclonal plasmacytosis, resulting in accumulation of clonal
      immunoglobulins. Monoclonal gammopathy of unknown significance (MGUS) is
      considered a premorbid stage for developing MM. Studies have shown an increased
      risk of MGUS in first-degree relatives of patients with MM. Detection of
      immunoglobulin heavy chain gene (IGH) rearrangement provides a useful tool for
      assessing clonality. The aim of this study was to determine clonality in
      peripheral blood samples from 61 healthy first-degree relatives of MM probands by
      sorting circulating lymphocytes and detection of the IGH rearrangements in these
      cells. We detected 16 out of 61 (26.2%) relatives with monoclonal complete and
      incomplete IGH rearrangements; only three of them showed elevated monoclonal
      immunoglobulin in the serum protein electrophoresis. We conclude that this
      strategy is able to identify efficiently clonality in peripheral blood samples
      from first-degree relatives of patients with MM, who have a non-negligible risk
      of developing MGUS or other plasma cell dyscrasias.

PMID- 24577940
TI  - Metabolic pathways related to oxidative stress in patients with hemoglobin h
      disease and iron overload.
AB  - BACKGROUND: Iron overload is a major complication in patients with hemoglobin H
      (Hb H) disease and causes damage of tissues. METHODS: We investigated 26 Hb H
      patients and 75 controls to evaluate their oxidative stress and antioxidant
      statuses. RESULTS: There were significantly increased levels of superoxide anion
      in leucocytes, nitrite (NO2-), and malondialdehyde (MDA) in plasma, and
      activities of superoxide dismutase (SOD), glutathione peroxidase (GPx),
      glutathione reductase (GRx) and oxidized glutathione (GSSG) in erythrocytes,
      decreased levels of nitrate (NO3-) and vitamin C in plasma, and reduced
      glutathione (GSH) in erythrocytes, in addition to the abnormal iron status in the
      patients when compared with those in the controls. Meanwhile, levels of serum
      ferritin were positively correlated with serum iron, plasma MDA, and erythrocyte
      SOD in the patients. In addition, the activities of SOD were positively
      correlated with those of GPx and GRx, and the levels of GSSG and MDA, but
      negatively correlated with those of GSH. Furthermore, the levels of MDA were
      negatively correlated those of vitamin C. CONCLUSIONS: These results demonstrate
      the presence of oxidative stress and decreased levels of antioxidants; moreover,
      the related metabolic antioxidant pathway is active in Hb H patients with iron
      overload.

PMID- 24577941
TI  - The use of Olaparib (AZD2281) potentiates SN-38 cytotoxicity in colon cancer
      cells by indirect inhibition of Rad51-mediated repair of DNA double-strand
      breaks.
AB  - Potent application of topoisomerase I inhibitor plus PARP inhibitor has been
      suggested to be an effective strategy for cancer therapy. Reportedly, mismatch
      repair (MMR)-deficient colon cancer cells are sensitive to topoisomerase I
      inhibitor, presumably due to microsatellite instability (MSI) of the MRE11 locus.
      We examined the synergy of SN-38, an active metabolite of irinotecan, in
      combination with the PARP inhibitor olaparib in colon cancer cells showing
      different MMR status, such as MSI or microsatellite stable (MSS) phenotype.
      Treatment with SN-38 and olaparib in combination almost halved the IC50 of SN-38
      for a broad spectrum of colon cancer cells independent of the MMR status.
      Furthermore, olaparib potentiated S-phase-specific double-strand DNA breaks (DSB)
      induced by SN-38, which is followed by Rad51 recruitment. siRNA-mediated
      knockdown of Rad51, but not Mre11 or Rad50, increased the sensitivity to olaparib
      and/or SN-38 treatment in colon cancer cells. In vivo study using mouse xenograft
      demonstrated that olaparib was effective to potentiate the antitumor effect of
      irinotecan. In conclusion, olaparib shows a synergistic effect in colon cancer
      cells in combination with SN-38 or irinotecan, potentiated by the Rad51-mediated
      HR pathway, irrespective of the Mre11-mediated failure of the MRN complex. These
      results may contribute to future clinical trials using PARP inhibitor plus
      topoisomerase I inhibitor in combination. Furthermore, the synergistic effect
      comprising topoisomerase I-mediated DNA breakage-reunion reaction, PARP and Rad51
      mediated HR pathway suggests the triple synthetic lethal pathways contribute to
      this event and are applicable as a potential target for future chemotherapy.

PMID- 24577942
TI  - Pharmacologic suppression of JAK1/2 by JAK1/2 inhibitor AZD1480 potently inhibits
      IL-6-induced experimental prostate cancer metastases formation.
AB  - Metastatic prostate cancer is lethal and lacks effective strategies for
      prevention or treatment, requiring novel therapeutic approaches. Interleukin-6
      (IL-6) is a cytokine that has been linked with prostate cancer pathogenesis by
      multiple studies. However, the direct functional roles of IL-6 in prostate cancer
      growth and progression have been unclear. In the present study, we show that IL-6
      is produced in distant metastases of clinical prostate cancers. IL-6-activated
      signaling pathways in prostate cancer cells induced a robust 7-fold increase in
      metastases formation in nude mice. We further show that IL-6 promoted migratory
      prostate cancer cell phenotype, including increased prostate cancer cell
      migration, microtubule reorganization, and heterotypic adhesion of prostate
      cancer cells to endothelial cells. IL-6-driven metastasis was predominantly
      mediated by Stat3 and to lesser extent by ERK1/2. Most importantly, pharmacologic
      inhibition of Jak1/2 by AZD1480 suppressed IL-6-induced signaling, migratory
      prostate cancer cell phenotypes, and metastatic dissemination of prostate cancer
      in vivo in nude mice. In conclusion, we demonstrate that the cytokine IL-6
      directly promotes prostate cancer metastasis in vitro and in vivo via Jak-Stat3
      signaling pathway, and that IL-6-driven metastasis can be effectively suppressed
      by pharmacologic targeting of Jak1/2 using Jak1/2 inhibitor AZD1480. Our results
      therefore provide a strong rationale for further development of Jak1/2 inhibitors
      as therapy for metastatic prostate cancer.

PMID- 24577944
TI  - The effects of micro arc oxidation of gamma titanium aluminide surfaces on
      osteoblast adhesion and differentiation.
AB  - The adhesion and proliferation of human fetal osteoblasts, hFOB 1.19, on micro
      arc oxidized (MAO) gamma titanium aluminide (gammaTiAl) surfaces were examined in
      vitro. Cells were seeded on MAO treated gammaTiAl disks and incubated for 3 days
      at 33.5  degrees C and subsequently for 7 days at 39.5  degrees C. Samples were
      then analyzed by scanning electron microscopy (SEM) and alkaline phosphatase
      assay (ALP) to evaluate cell adhesion and differentiation, respectively. Similar
      Ti-6Al-4V alloy samples were used for comparison. Untreated gammaTiAl and Ti-6Al
      4V disks to study the effect of micro arc oxidation and glass coverslips as cell
      growth controls were also incubated concurrently. The ALP Assay results, at 10
      days post seeding, showed significant differences in cell differentiation, with P
      values <0.05 between MAO gammaTiAl and MAO Ti-6Al-4V with respect to the
      corresponding untreated alloys. While SEM images showed that hFOB 1.19 cells
      adhered and proliferated on all MAO and untreated surfaces, as well as on glass
      coverslips at 10 days post seeding, cell differentiation, determined by the ALP
      assay, was significantly higher for the MAO alloys.

PMID- 24577943
TI  - Effects of the polymeric niche on neural stem cell characteristics during primary
      culturing.
AB  - The polymeric niche encountered by cells during primary culturing can affect cell
      fate. However, most cell types are primarily propagated on polystyrene (PS). A
      cell type specific screening for optimal primary culture polymers particularly
      for regenerative approaches seems inevitable. The effect of physical and chemical
      properties of treated (corona, oxygen/nitrogen plasma) and untreated cyclic
      olefin polymer (COP), polymethymethacrylate (PMMA), PP, PLA, PS, PC on neuronal
      stem cell characteristics was analyzed. Our comprehensive approach revealed
      plasma treated COP and PMMA as optimal polymers for primary neuronal stem cell
      culturing and propagation. An increase in the number of NT2/D1 cells with
      pronounced adhesion, metabolic activities and augmented expression of neural
      precursor markers was associated to the plasma treatment of surfaces of COP and
      PMMA with nitrogen or oxygen, respectively. A shift towards large cell sizes at
      stable surface area/volume ratios that might promote the observed increase in
      metabolic activities and distinct modulations in F-actin arrangements seem to be
      primarily mediated by the plasma treatment of surfaces. These results indicate
      that the polymeric niche has a distinct impact on various cell characteristics.
      The selection of distinct polymers and the controlled design of an optimized
      polymer microenvironment might thereby be an effective tool to promote essential
      cell characteristics for subsequent approaches.

PMID- 24577945
TI  - Cellulose film regenerated from Styela clava tunics have biodegradability,
      toxicity and biocompatibility in the skin of SD rats.
AB  - Cellulose is one of the most widespread biomolecules in nature and has been
      exploited in various applications including scaffolding, tissue engineering, and
      tissue formation. To evaluate the biocompatibility of cellulose film manufactured
      from Styela clava tunics (SCT-CF), these films were implanted in Sprague-Dawley
      (SD) rats for various lengths of time, after which they were subjected to
      mechanical and biological analyses. The cellulose powders (12-268 m) obtained
      from SCT was converted into films via casting methods without adding any
      additives. SCT-CF contained about 98 % alpha-cellulose and very low
      concentrations of betabeta-cellulose. Additionally, the crystallinity index (CrI)
      of SCT-CF was lower (10.71 %) than that of wood pulp-cellulose films (WP-CF)
      (33.78 %). After implantation for 90 days, the weight loss and formation of
      surface corrugations were greater in SCT-CF than that of WP-CF, while the surface
      roughness was significantly higher in WP-CF than SCT-CF. However, there were no
      differences in the number of white blood cells between SCT-CF implanted rats and
      vehicle implanted rats. The level of metabolic enzymes representing liver and
      kidney toxicity in the serum of SCT-CF implanted rats was maintained at levels
      consistent with vehicle implanted rats. Moreover, no significant alteration of
      the epidermal hyperplasia, inflammatory cell infiltration, redness, and edema
      were observed in SD rats implanted with SCT-CF. Taken together, these results
      indicate that SCT-CF showed good degradability and non-toxicity without inducing
      an immune response in SD rats. Further, the data presented here constitute strong
      evidence that SCT-CF has the potential for use as a powerful biomaterial for
      medical applications including stitching fiber, wound dressing, scaffolding,
      absorbable hemostats and hemodialysis membrane.

PMID- 24577948
TI  - On the configurational stability of chiral, nonracemic fluoro- and iodo
      [D(1)]methyllithiums.
AB  - Enantiomerically pure fluoro-[D1]methyllithium and iodo-[D1]methyllithiums of up
      to 92% ee were generated by transmetalation of the corresponding stannanes with
      MeLi in THF at various temperatures. The intermediate halo-[D1]methyllithiums
      were trapped with benzaldehyde or acetophenone already present in excess in the
      reaction mixture to either give halohydrins or to disintegrate to carbene. The
      fluoro-[D1]methyllithiums were found to be microscopically configurationally
      stable within the tested range of -95 to 0  degrees C, but chemically only stable
      at temperatures below -95  degrees C due to a rapidly increasing portion
      disintegrating to carbene. The iodo-[D1]methyllithiums were configurationally
      labile relative to the rate of addition to PhCHO at all temperatures tested (-95
      to -30  degrees C). Disintegration to carbene interfered as well.

PMID- 24577949
TI  - Impact of right-ventricular apical pacing on the optimal left-ventricular lead
      positions measured by phase analysis of SPECT myocardial perfusion imaging.
AB  - PURPOSE: The use of SPECT phase analysis to optimize left-ventricular (LV) lead
      positions for cardiac resynchronization therapy (CRT) was performed at baseline,
      but CRT works as simultaneous right ventricular (RV) and LV pacing. The aim of
      this study was to assess the impact of RV apical (RVA) pacing on optimal LV lead
      positions measured by SPECT phase analysis. METHODS: This study prospectively
      enrolled 46 patients. Two SPECT myocardial perfusion scans were acquired under
      sinus rhythm with complete left bundle branch block and RVA pacing, respectively,
      following a single injection of (99m)Tc-sestamibi. LV dyssynchrony parameters and
      optimal LV lead positions were measured by the phase analysis technique and then
      compared between the two scans. RESULTS: The LV dyssynchrony parameters were
      significantly larger with RVA pacing than with sinus rhythm (p ~0.01). In 39 of
      the 46 patients, the optimal LV lead positions were the same between RVA pacing
      and sinus rhythm (kappa = 0.861). In 6 of the remaining 7 patients, the optimal
      LV lead positions were along the same radial direction, but RVA pacing shifted
      the optimal LV lead positions toward the base. CONCLUSION: The optimal LV lead
      positions measured by SPECT phase analysis were consistent, no matter whether the
      SPECT images were acquired under sinus rhythm or RVA pacing. In some patients,
      RVA pacing shifted the optimal LV lead positions toward the base. This study
      supports the use of baseline SPECT myocardial perfusion imaging to optimize LV
      lead positions to increase CRT efficacy.

PMID- 24577950
TI  - PET/MRI and PET/CT in follow-up of head and neck cancer patients.
AB  - PURPOSE: Positron emission tomography (PET)/MRI combines the functional ability
      of PET and the high soft tissue contrast of MRI. The aim of this study was to
      assess contrast-enhanced (ce)PET/MRI compared to cePET/CT in patients with
      suspected recurrence of head and neck cancer (HNC). METHODS: Eighty-seven
      patients underwent sequential cePET/CT and cePET/MRI using a trimodality PET/CT
      MRI set-up. Diagnostic accuracy for the detection of recurrent HNC was evaluated
      using cePET/CT and cePET/MRI. Furthermore, image quality, presence of unclear
      (18)F-fluorodeoxy-D-glucose (FDG) findings of uncertain significance and the
      diagnostic advantages of use of gadolinium contrast enhancement were analysed.
      RESULTS: cePET/MRI showed no statistically significant difference in diagnostic
      accuracy compared to cePET/CT (91.5 vs 90.6%). Artefacts' grade was similar in
      both methods, but their location was different. cePET/CT artefacts were primarily
      located in the suprahyoid area, while on cePET/MRI, artefacts were more equally
      distributed among the supra and infrahyoid neck regions. cePET/MRI and cePET/CT
      showed 34 unclear FDG findings; of those 11 could be solved by cePET/MRI and 5 by
      cePET/CT. The use of gadolinium in PET/MRI did not yield higher diagnostic
      accuracy, but helped to better define tumour margins in 6.9% of patients.
      CONCLUSION: Our data suggest that cePET/MRI may be superior compared to cePET/CT
      to specify unclear FDG uptake related to possible tumour recurrence in follow-up
      of patients after HNC. It seems to be the modality of choice for the evaluation
      of the oropharynx and the oral cavity because of a higher incidence of artefacts
      in cePET/CT in this area mainly due to dental implants. However, overall there is
      no statistically significant difference.

PMID- 24577951
TI  - Radiation dosimetry and first therapy results with a (124)I/ (131)I-labeled small
      molecule (MIP-1095) targeting PSMA for prostate cancer therapy.
AB  - INTRODUCTION: Since the prostate-specific membrane antigen (PSMA) is frequently
      over-expressed in prostate cancer (PCa) several PSMA-targeting molecules are
      under development to detect and treat metastatic castration resistant prostate
      cancer (mCRPC). We investigated the tissue kinetics of a small molecule inhibitor
      of PSMA ((S)-2-(3-((S)-1-carboxy-5-(3-(4
      [(124)I]iodophenyl)ureido)pentyl)ureido)pentanedioicacid; MIP-1095) using PET/CT
      to estimate radiation dosimetry for the potential therapeutic use of (131)I-MIP
      1095 in men with mCRPC. We also report preliminary safety and efficacy of the
      first 28 consecutive patients treated under a compassionate-use protocol with a
      single cycle of (131)I-MIP-1095. METHODS: Sixteen patients with known prostate
      cancer underwent PET/CT imaging after i.v. administration of (124)I-MIP-1095
      (mean activity: 67.4 MBq). Each patient was scanned using PET/CT up to five times
      at 1, 4, 24, 48 and 72 h post injection. Volumes of interest were defined for
      tumor lesions and normal organs at each time point followed by dose calculations
      using the OLINDA/EXM software. Twenty-eight men with mCRPC were treated with a
      single cycle of (131)I-MIP-1095 (mean activity: 4.8 GBq, range 2 to 7.2 GBq) and
      followed for safety and efficacy. Baseline and follow up examinations included a
      complete blood count, liver and kidney function tests, and measurement of serum
      PSA. RESULTS: I-124-MIP-1095 PET/CT images showed excellent tumor uptake and
      moderate uptake in liver, proximal intestine and within a few hours post
      injection also in the kidneys. High uptake values were observed only in salivary
      and lacrimal glands. Dosimetry estimates for I-131-MIP-1095 revealed that the
      highest absorbed doses were delivered to the salivary glands (3.8 mSv/MBq, liver
      (1.7 mSv/MBq) and kidneys (1.4 mSv/MBq). The absorbed dose calculated for the red
      marrow was 0.37 mSv/MBq. PSA values decreased by >50 % in 60.7 % of the men
      treated. Of men with bone pain, 84.6 % showed complete or moderate reduction in
      pain. Hematological toxicities were mild. Of men treated, 25 % had a transient
      slight to moderate dry mouth. No adverse effects on renal function were observed.
      CONCLUSION: Based on the biodistribution and dose calculations of the PSMA
      targeted small molecule (124)I-MIP-1095 therapy with the authentic analog (131)I
      MIP-1095 enables a targeted tumor therapy with unprecedented doses delivered to
      the tumor lesions. Involved lymph node and bone metastases were exposed to
      estimated absorbed doses upwards of 300 Gy.

PMID- 24577952
TI  - Sites of latest mechanical activation as assessed by SPECT myocardial perfusion
      imaging in ischemic and dilated cardiomyopathy patients with LBBB.
AB  - OBJECTIVE: Sites of latest mechanical activation (SOLA) have been recognized as
      optimal left-ventricular (LV) lead positions for cardiac resynchronization
      therapy (CRT). This study was aimed to investigate SOLA in ischemic
      cardiomyopathy (ICM) and dilated cardiomyopathy (DCM) patients with left bundle
      branch block (LBBB). METHODS: Sixty-four consecutive LBBB patients (47 DCM, 17
      ICM), who met the standard indications for CRT and underwent resting SPECT
      myocardial perfusion imaging (MPI), were selected. Phase analysis was used to
      assess LV dyssynchrony and SOLA. The Emory Cardiac Toolbox was used to measure
      perfusion defects. LV dyssynchrony and SOLA were compared between the DCM
      patients with wide (>=150 ms) and moderate (120-150 ms) QRS durations (QRSd). The
      relationship between SOLA and perfusion defects was analyzed in the ICM patients.
      RESULTS: The DCM patients with wide QRSd had significantly more LV dyssynchrony
      than those with moderate QRSd. Lateral SOLA were significantly more frequent in
      the DCM patients with wide QRSd than those with moderate QRSd (96% vs. 62%, p =
      0.010). In the ICM patients, SOLA were either in the scar segments (82%) or in
      the segments immediately adjacent to the scar segments (18%), regardless of QRSd.
      CONCLUSION: Lateral SOLA were more frequent in the DCM patients with wide QRSd
      than those with moderate QRSd. Such relationship was not observed in the ICM
      patients, where SOLA were associated with scar location rather than QRSd. These
      findings support the use of SPECT MPI to aid the selection of potential CRT
      responders and guide LV lead placement.

PMID- 24577955
TI  - Is it time to move beyond errors in clinical reasoning and discuss accuracy?

PMID- 24577953
TI  - Bone and joint infections due to anaerobic bacteria: an analysis of 61 cases and
      review of the literature.
AB  - The diagnosis of anaerobic bone and joint infections (BJI) were underestimated
      before the advent of molecular identification and matrix-assisted laser
      desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). We report
      61 cases of anaerobic infections based on our 4-year experience with the
      management of BJI. A total of 75% of cases were post-surgical infections,
      associated with osteosynthesis devices (65%). Early infections occurred in 27% of
      cases, delayed infections in 17.5% of cases, and late infections in 55% of cases.
      We recorded 36 species of 93 anaerobic strains using MALDI-TOF MS (91) and
      molecular methods (2). We identified 20 strains of Propionibacterium acnes, 13 of
      Finegoldia magna, six of Peptoniphilus asaccharolyticus, and six of P. harei.
      Polymicrobial infections occurred in 50 cases. Surgical treatment was performed
      in 93.5% of cases. The antibiotic treatments included amoxicillin (30%),
      amoxicillin-clavulanic acid (16%), metronidazole (30%), and clindamycin (26%).
      Hyperbaric oxygen therapy was used in 17 cases (28%). The relapse rate (27%) was
      associated with lower limbs localization (p = 0.001). P. acnes BJI was associated
      with shoulder (p = 0.019), vertebra (p = 0.021), and head flap localization (p =
      0.011), and none of these cases relapsed (p = 0.007). F. magna BJI was associated
      with ankle localization (p = 0.014). Anaerobic BJI is typically considered as a
      post-surgical polymicrobial infection, and the management of this infection
      combines surgical and medical treatments. MALDI-TOF MS and molecular
      identification have improved diagnosis. Thus, physicians should be aware of the
      polymicrobial nature of anaerobic BJI to establish immediate broad-spectrum
      antibiotic treatment during the post-surgical period until accurate
      microbiological results have been obtained.

PMID- 24577954
TI  - Comparative pharmacokinetics of active alkaloids after oral administration of
      Rhizoma Coptidis extract and Wuji Wan formulas in rat using a UPLC-MS/MS method.
AB  - Wuji Wan (WJW), containing Rhizoma Coptidis (Huanglian in Chinese, HL), Frutus
      Evodiae Rutaecarpae (Wuzhuyu, WZY) and Radix Paeoniae Alba (Baishao, BS), is a
      classical traditional Chinese medical formula employed in treating intestinal
      disorders. Berberine (BBR) and palmatine (PMT) are the major active alkaloids in
      HL and have analgesic and anti-microbial effects. A sensitive, specific and
      validated ultra-performance liquid chromatography-tandem mass spectrometric
      method was developed to investigate the pharmacokinetic profiles of BBR and PMT
      in rat plasma and in situ intestinal perfusion solution. In comparison with the
      pharmacokinetic parameters of BBR and PMT, t(1/2), C(max), T(max), AUC, CL and
      MRT after intragastric (i.g.) administration with HL extract alone, those
      remarkably changed after i.g. administration with WJW formulas 1 and 2 (herb
      proportions are 12:2:3 and 12:1:12). Particularly, the oral bioavailability of
      PMT in WJW formula 1 was significantly increased. In rat intestinal perfusion
      experiments, the apparent permeability coefficient value of PMT was (1.45 +/-
      0.72) * 10(-5) cm/s when perfusion with HL was performed, and the value was
      significantly increased to (3.92 +/- 0.52) * 10(-5) cm/s on perfusion with WJW
      formula 1. These results indicate that the pharmacokinetic parameters and
      absorption of BBR and PMT are affected by the other herbs or ingredients from WJW
      formulas.

PMID- 24577956
TI  - Increasing complexity of high-grade B-cell lymphomas.

PMID- 24577957
TI  - Fluorescent leukocytes enter plaque on the microscope stage.

PMID- 24577958
TI  - Embracing bias: beta1-adrenergic receptor-biased ligands and nuclear miRNA
      processing.

PMID- 24577959
TI  - Cardiovascular twist to the rapidly evolving apolipoprotein L1 story.

PMID- 24577960
TI  - Clinical benefits of remote ischemic preconditioning: new insights...and new
      questions.

PMID- 24577961
TI  - Specific RNA inhibition of causal alleles: a potential therapy for familial
      hypertrophic cardiomyopathy.

PMID- 24577962
TI  - Angiotensin II, from vasoconstrictor to growth factor: a paradigm shift.

PMID- 24577963
TI  - Perspective on the 2013 American Heart Association/American College of Cardiology
      guideline for the use of statins in primary prevention of low-risk individuals.

PMID- 24577964
TI  - The 2013 ACC/AHA guidelines on the treatment of blood cholesterol: questions,
      questions, questions.

PMID- 24577967
TI  - Myocardial extracellular matrix: an ever-changing and diverse entity.
AB  - The cardiac extracellular matrix (ECM) is a complex architectural network
      consisting of structural and nonstructural proteins, creating strength and
      plasticity. The nonstructural compartment of the ECM houses a variety of
      proteins, which are vital for ECM plasticity, and can be divided into 3 major
      groups: glycoproteins, proteoglycans, and glycosaminoglycans. The common
      denominator for these groups is glycosylation, which refers to the decoration of
      proteins or lipids with sugars. This review will discuss the fundamental role of
      the matrix in cardiac development, homeostasis, and remodeling, from a
      glycobiology point of view. Glycoproteins (eg, thrombospondins, secreted protein
      acidic and rich in cysteine, tenascins), proteoglycans (eg, versican, syndecans,
      biglycan), and glycosaminoglycans (eg, hyaluronan, heparan sulfate) are
      upregulated on cardiac injury and regulate key processes in the remodeling
      myocardium such as inflammation, fibrosis, and angiogenesis. Albeit some
      parallels can be made regarding the processes these proteins are involved in,
      their specific functions are extremely diverse. In fact, under varying
      conditions, individual proteins can even have opposing functions, making
      spatiotemporal contribution of these proteins in the rearrangement of
      multifaceted ECM very hard to grasp. Alterations of protein characteristics by
      the addition of sugars may explain the immense, yet tightly regulated,
      variability of the remodeling cardiac matrix. Understanding the role of
      glycosylation in altering the ultimate function of glycoproteins, proteoglycans,
      and glycosaminoglycans in the myocardium may lead to the development of new
      biochemical structures or compounds with great therapeutic potential for patients
      with heart disease. 

PMID- 24577968
TI  - Matrix as an interstitial transport system.
AB  - The extracellular matrix (ECM) is best known for its function as a structural
      scaffold for the tissue and more recently as a microenvironment to sequester
      growth factors and cytokines allowing for rapid and localized changes in their
      activity in the absence of new protein synthesis. In this review, we explore this
      and additional new aspects of ECM function in mediating cell-to-cell
      communications. Fibrillar and nonfibrillar components of ECM can limit and
      facilitate the transport of molecules through the extracellular space while also
      regulating interstitial hydrostatic pressure. In turn, transmembrane
      communications via molecules, such as ECM metalloproteinase inducer,
      thrombospondins, and integrins, can further mediate cell response to
      extracellular cues and affect ECM composition and tissue remodeling. Other means
      of cell-to-cell communication include extracellular microRNA transport and its
      contribution to gene expression in target cells and the nanotube formation
      between distant cells, which has recently emerged as a novel conduit for
      intercellular organelle sharing thereby influencing cell survival and function.
      The information summarized and discussed here are not limited to the
      cardiovascular ECM but encompass ECM in general with specific references to the
      cardiovascular system. 

PMID- 24577969
TI  - Molecular imaging of the cardiac extracellular matrix.
AB  - In almost all cardiac diseases, an increase in extracellular matrix (ECM)
      deposition or fibrosis occurs, mostly consisting of collagen I. Whereas
      replacement fibrosis follows cardiomyocyte loss in myocardial infarction,
      reactive fibrosis is triggered by myocardial stress or inflammatory mediators and
      often results in ventricular stiffening, functional deterioration, and
      development of heart failure. Given the importance of ECM deposition in cardiac
      disease, ECM imaging could be a valuable clinical tool. Molecular imaging of ECM
      may help understand pathology, evaluate impact of novel therapy, and may
      eventually find a role in predicting the extent of ECM expansion and development
      of personalized treatment. In the current review, we provide an overview of ECM
      imaging including the assessment of ECM volume and molecular targeting of key
      players involved in ECM deposition and degradation. The targets comprise
      myofibroblasts, intracardiac renin-angiotensin axis, matrix metalloproteinases,
      and matricellular proteins. 

PMID- 24577966
TI  - Translating Koch's postulates to identify matrix metalloproteinase roles in
      postmyocardial infarction remodeling: cardiac metalloproteinase actions (CarMA)
      postulates.
AB  - The first matrix metalloproteinase (MMP) was described in 1962; and since the
      1990s, cardiovascular research has focused on understanding how MMPs regulate
      many aspects of cardiovascular pathology from atherosclerosis formation to
      myocardial infarction and stroke. Although much information has been gleaned by
      these past reports, to a large degree MMP cardiovascular biology remains
      observational, with few studies homing in on cause and effect relationships.
      Koch's postulates were first developed in the 19th century as a way to establish
      microorganism function and were modified in the 20th century to include methods
      to establish molecular causality. In this review, we outline the concept for
      establishing a similar approach to determine causality in terms of MMP functions.
      We use left ventricular remodeling postmyocardial infarction as an example, but
      this approach will have broad applicability across both the cardiovascular and
      the MMP fields. 

PMID- 24577970
TI  - Dynamic changes in myocardial matrix and relevance to disease: translational
      perspectives.
AB  - The cardiac extracellular matrix (ECM) provides the architectural scaffold to
      support efficient contraction and relaxation of cardiomyocytes. The elegant
      design of the ECM facilitates optimal force transduction, electric transmission,
      intercellular communication, and metabolic exchange within the myocardial
      microenvironment. In the setting of increased wall stress, injury, or disease,
      the ECM can undergo a series of dynamic changes that lead to favorable chamber
      remodeling and functional adaptation. Over time, sustained matrix remodeling can
      impair diastolic and systolic function caused by excess deposition of
      interstitial fibrous tissue. These pathological alterations in ECM
      structure/function are considered central to the evolution of adverse cardiac
      remodeling and the development of heart failure. This review discusses the
      complex dynamics of the cardiac ECM in the setting of myocardial infarction,
      pressure overload, and volume overload. We also summarize the current status of
      ECM biomarkers that may have clinical value in prognosticating cardiac disease
      progression in patients. Finally, we discuss the most current status of drugs
      under evaluation for use in cardiac fibrosis. 

PMID- 24577971
TI  - Randomized controlled trial of Nuevo Amanecer: a peer-delivered stress management
      intervention for Spanish-speaking Latinas with breast cancer.
AB  - BACKGROUND: Latinas with breast cancer suffer symptom and psychosocial health
      disparities. Effective interventions have not been developed for or tested in
      this population. PURPOSE: We describe community-based participatory research
      methods used to develop and implement the Nuevo Amanecer program, a culturally
      tailored, peer-delivered cognitive-behavioral stress management intervention for
      low-income Spanish-speaking Latinas with breast cancer, and unique considerations
      in implementing a randomized controlled trial to test the program in community
      settings. METHODS: We applied an implementation science framework to delineate
      the methodological phases used to develop and implement the Nuevo Amanecer
      program and trial, emphasizing community engagement processes. RESULTS: In phase
      1, we established project infrastructure: academic and community co-principal
      investigators, community partners, community advisory board, steering committee,
      and funding. In phase 2, we identified three program inputs: formative research,
      a community best-practices model, and an evidence-based intervention tested in
      non-Latinas. In phase 3, we created the new program by integrating and adapting
      intervention components from the three sources, making adaptations to accommodate
      low literacy, Spanish language, cultural factors, community context, and
      population needs. In phase 4, we built community capacity for the program and
      trial by training field staff (recruiters and interventionists embedded in
      community sites), compensating field staff, and creating a system for identifying
      potential participants. In phase 5, we implemented and monitored the program and
      trial. Engaging community partners in all phases has resulted in a new,
      culturally tailored program that is suitable for newly diagnosed Latinas with
      breast cancer and a trial that is acceptable and supported by community and
      clinical partners. Lessons learned Engagement of community-based organizations
      and cancer survivors as research partners and hiring recruiters and
      interventionists from the community were critical to successful implementation in
      community settings. Having culturally and linguistically competent research staff
      with excellent interpersonal skills facilitated implementation. Facilitating and
      maintaining excellent communication among community partners was imperative to
      troubleshoot implementation issues. Randomization was challenging due to
      community concerns about assigning women to a control group. Patient privacy
      regulations and the need for extensive outreach to establish relationships
      between community partners and clinical sites hampered initial recruitment.
      LIMITATIONS: These were resource-intensive processes to develop and implement the
      program that need to be compared to less-intensive alternatives. CONCLUSION:
      Engaging community members in design and implementation of community-based
      programs and trials enhances cultural appropriateness and congruence with the
      community context. If the randomized trial demonstrates that the intervention is
      effective, it will fill a gap in evidence-based programs to address ethnic
      disparities in quality of life among Spanish-speaking Latinas with breast cancer.

PMID- 24577973
TI  - Urinary tract infections caused by extended-spectrum betalactamase-producing
      bacteria in children: a matched casecontrol study.
AB  - Extended-spectrum beta-lactamase (ESBL)-producing pathogens are emerging as a
      cause of urinary tract infections (UTI) worldwide. In this matched-case control
      study, clinical characteristics and associated risk factors for ESBL UTI were
      evaluated. In a total of 463 positive urine cultures, 48 (10.4%) (from 39
      patients, 23 boys) were phenotypically ESBL-producing bacteria. The most
      frequently isolated microorganism was , followed by Klebsiella spp. and
      Enterobacter cloacae. Children with ESBL UTI (n=39) were on prophylaxis more (21%
      vs. 6%, p=0.01), had higher rates of urinary tract anomalies (36% vs. 10%,
      p=0.0007), presented abnormal 99m Tcdimercaptosuccinic acid (DMSA) findings (i.e.
      scars) (23% vs. 4%, p=0.001), and had longer hospitalization (9.8 vs. 7.4 days,
      p=0.004) compared to those with non-ESBL UTI (n=117). The recognition of risk
      factors for UTI caused by ESBL bacteria in children may aid in the identification
      of high-risk cases and may enable proper management of these patients. 

PMID- 24577974
TI  - Risk factors for nasopharyngeal carriage of Streptococcus pneumoniae in healthy
      Turkish children after the addition of heptavalent pneumococcal conjugate vaccine
      (PCV7) to the national vaccine schedule.
AB  - The purpose of this study was to investigate the effects of pneumococcal
      conjugate vaccine (PCV7) on nasopharyngeal (NP) carriage rates of Streptococcus
      pneumoniae in healthy Turkish children. The study was conducted on 1101 healthy
      Turkish children between 1 month and 18 years of age. The median and mean ages of
      the children were 25 months (1 month-18 years) and 45.7+/-49.6 months,
      respectively. S. pneumoniae was isolated in 241/1101 (21.9%) children included in
      the study. According to multivariate analysis, being <5 years of age, presence of
      a child attending a daycare center, recovery from respiratory infection within
      the last month, low income level of the family, and presence of more children in
      the family were found to be the risk factors for the NP pneumococcal carriage.
      The carriage rate of NP pneumococci in healthy children was not influenced by
      PCV7 in Turkey. 

PMID- 24577975
TI  - Congenital hyperinsulinism presenting with different clinical, biochemical and
      molecular genetic spectra.
AB  - Congenital hyperinsulinism (CHI) is a common cause of hypoglycemia in infants. We
      report three cases of CHI with differing clinical, biochemical, and molecular
      genetic spectra. One patient was unresponsive to medical treatment and died after
      subtotal pancreatectomy because of complications due to the surgery. Two patients
      have been followed successfully with medical treatment. Early diagnosis and
      appropriate treatment of CHI are essential to prevent morbidity and mortality. 

PMID- 24577972
TI  - Implementing trials of complex interventions in community settings: the USC
      Rancho Los Amigos pressure ulcer prevention study (PUPS).
AB  - BACKGROUND: Randomized trials of complex, non-pharmacologic interventions
      implemented in home and community settings, such as the University of Southern
      California (USC)-Rancho Los Amigos National Rehabilitation Center (RLANRC)
      Pressure Ulcer Prevention Study (PUPS), present unique challenges with respect to
      (1) participant recruitment and retention, (2) intervention delivery and
      fidelity, (3) randomization and assessment, and (4) potential inadvertent
      treatment effects. PURPOSE: We describe the methods employed to address the
      challenges confronted in implementing PUPS. In this randomized controlled trial,
      we are assessing the efficacy of a complex, preventive intervention in reducing
      the incidence of, and costs associated with, the development of medically serious
      pressure ulcers in people with spinal cord injury. METHODS: Individuals with
      spinal cord injury recruited from RLANRC were assigned to either a 12-month
      preventive intervention group or a standard care control group. The primary
      outcome is the incidence of serious pressure ulcers with secondary endpoints
      including ulcer-related surgeries, medical treatment costs, and quality of life.
      These outcomes are assessed at 12 and 24 months after randomization.
      Additionally, we are studying the mediating mechanisms that account for
      intervention outcomes. RESULTS: PUPS has been successfully implemented, including
      recruitment of the target sample size of 170 participants, assurance of the
      integrity of intervention protocol delivery with an average 90% treatment
      adherence rate, and enactment of the assessment plan. However, implementation has
      been replete with challenges. To meet recruitment goals, we instituted a five
      pronged approach customized for an underserved, ethnically diverse population. In
      intervention delivery, we increased staff time to overcome economic and cultural
      barriers to retention and adherence. To ensure treatment fidelity and
      replicability, we monitored intervention protocol delivery in accordance with a
      rigorous plan. Finally, we have overcome unanticipated assessment and design
      concerns related to (1) determining pressure ulcer incidence/severity, (2)
      randomization imbalance, and (3) inadvertent potential control group
      contamination. LIMITATIONS: We have addressed the most daunting challenges
      encountered in the recruitment, assessment, and intervention phases of PUPS. Some
      challenges and solutions may not apply to trials conducted in other settings.
      CONCLUSIONS: Overcoming challenges has required a multifaceted approach
      incorporating individualization, flexibility, and persistence, as well as the
      ability to implement needed mid-course corrections.

PMID- 24577977
TI  - Cord blood cytokine levels in focal early-onset neonatal infection after preterm
      premature rupture of membranes.
AB  - This study aimed to evaluate the levels of pro- and anti-inflammatory cytokines
      in umbilical cord blood of preterm neonates who developed focal early-onset
      infection (EOI) after preterm premature rupture of membranes (PPROM). This is a
      prospective study conducted on 46 preterm infants from mothers with PPROM. The
      cytokines were measure by flow cytometry. Newborns were classified into two
      groups as focal EOI (n=19) and non-infected (n=27). Interleukin (IL)-6 and IL-8
      levels were higher, whereas IL-10 and IL-12 p70 levels were lower in the EOI when
      compared to the non-infected group. The best combination of cytokines was IL-6+IL
      8, with a diagnostic accuracy of 0.97. Focal EOI after PPROM is associated with
      increased levels of IL-6 and IL-8 and diminished IL-10 and IL-12 in the cord
      blood of preterm infants. Combined assessment of IL-6 and IL-8 in cord blood may
      provide an additional tool for identifying preterm infants who develop EOI after
      PPROM. 

PMID- 24577976
TI  - Usefulness of long-term video-EEG monitoring in children at a tertiary care
      center.
AB  - The value of video-electroencephalographic monitoring (EEG-VM) in evaluating
      patients with epileptic disorders constitutes a major research field. This study
      investigates the usefulness of inpatient long-term EEG-VM for pediatric neurology
      patients under four headings: pre-surgical evaluation; seizure classification;
      epileptic seizure and non-epileptic paroxysmal event differentiation; and
      antiepileptic drug (AED) treatment modification. A retrospective study of 101
      patients over a one-year period was carried out. The results showed that
      following EEG-VM, 57.4% of the patients were referred for discussion to the
      epilepsy surgery conference regarding resective surgery, and of these, 31% were
      deemed to be surgical candidates. The seizure classification assigned to the
      patients before EEG-VM changed in 73.3% of the patients after EEG-VM. Regarding
      the differentiation between epileptic seizure and non-epileptic paroxysmal
      events, a diagnosis of psychogenic non-epileptic seizure (PNES) was made in 4% of
      the patients after EEG-VM. EEG-VM outcomes led to the modification of AED
      treatment in 68.3% of the patients. These significant alterations demonstrate the
      usefulness of EEG-VM in the management of pediatric neurology patients. 

PMID- 24577978
TI  - Evaluation of hearing and speech-language in preschool children: how important,
      why we should perform?
AB  - The aim of the study was to present the hearing and speech-language findings of
      preschool children. The children in this study were aged 3-5 years. Sixtyseven of
      239 children (28.0%) had been referred to a physician because of possible middle
      ear problems, and 25 of the 67 children had slight and mild conduction type
      hearing loss with air-bone gaps. One of 239 children had profound sensorineural
      hearing loss. Speech-language problems were found in 70 of 239 children (29.3%).
      Necessary attention should be paid to the evaluation of hearing and speech
      language skills in preschool-aged children to avoid delayed detection and to give
      these children the opportunity for timely intervention for hearing and speech
      language problems. 

PMID- 24577979
TI  - Renal outcome of children with unilateral renal agenesis.
AB  - The aim of this study was to evaluate associated urological anomalies and renal
      outcome in children with unilateral renal agenesis (URA). Medical records of 51
      cases of URA followed at Sanliurfa Children 's Hospital between January 2009 and
      December 2012 were reviewed retrospectively. In all patients, diagnosis was made
      by abdominal ultrasound (US) and confirmed by a radionuclide scan. The children
      were between 3 months and 17 years of age (median age: 5 years). There were 31
      males (60.8%) and 20 females (39.2%). In 33 patients (67.3%), the left kidney was
      absent. Urological anomalies were found in 12/51 patients (23.5%), including
      ureterovesical junction obstruction in 4 (7.8%), bladder dysfunction in 2 (3.9%),
      and vesicoureteral reflux (VUR), ureteropelvic junction obstruction,
      ureterovesical and ureteropelvic junction obstruction, duplicated collecting
      system plus grade IV VUR, ectopic kidney plus grade V VUR, and ectopic kidney in
      1 patient (2%) each. Chronic renal insufficiency (CRI) developed in 5/51 patients
      (9.8%) (stage III in 3 patients and stage IV in 2), 4 of whom had additional
      urological anomaly; in the remaining 1 patient, a 17-year-old female, imaging
      studies were normal except for a small and hyperechogenic solitary kidney
      determined on US. A total of 3 patients (5.8%) developed hypertension, and all
      except one had an associated urological anomaly. Proteinuria was seen in 2
      patients (3.8%) with stage IV CRI, one of whom was also hypertensive. In
      conclusion, urological anomalies usually accompany URA and should be followed
      closely to decrease the risk of renal failure. 

PMID- 24577980
TI  - Cholestasis in infants with immune hydrops fetalis.
AB  - Rhesus (Rh) hemolytic disease of the newborn represents a broad spectrum of
      symptoms in the fetus and newborn, ranging from mild to severe hemolytic anemia
      and hydrops fetalis. Cholestasis is a common problem in infants with immune
      hydrops fetalis (IHF). The aim of this study was to evaluate the incidence and
      course of cholestasis in infants with IHF due to Rh alloimmunization. Infants
      with IHF during the 10-year follow-up were retrospectively included in the study.
      Demographics, laboratory parameters, and prenatal and postnatal interventions
      were recorded. The incidence of cholestasis and certain risk factors were
      investigated. A total of 30 infants with IHF with a mean gestational age 33 +/-
      2.6 weeks were included. Of these, 15 infants (50%) survived to discharge. The
      incidence of cholestasis was 60% (18/30). Cholestasis was diagnosed within a
      median 3 (0-7) days. All cholestatic infants who survived recovered within three
      months. In conclusion, cholestasis in IHF is frequent, transient and has an early
      onset. 

PMID- 24577981
TI  - Drowning and near-drowning: experience of a university hospital in the Black Sea
      region.
AB  - The aim of the study was to describe the characteristics of patients who applied
      to the Emergency Department (ED) due to submersion injury; to recognize the risk
      factors, complications, causes of death, and the educational needs of families
      and caregivers about unsafe environments for submersion; and to develop
      preventive strategies. All patients were analyzed retrospectively according to
      demographic features, clinical and laboratory findings, association between
      clinical variables and submersion injuries, and patient outcomes. Fifty-five
      patients with submersion injury were analyzed. The mean age of patients was 10.9
      +/- 4.7 years. The most common Szpilman clinical scores were Grade 1 (24
      patients, 43.8%), Grade 2 (15 patients, 27.3%), and Grade 5 (10 patients, 18.2%).
      The common location of the submersion injuries included the sea (74.5%), pool
      (18.4%), bathtub (7.3%), river (3.6%), and lake (3.6%). A limited swimming
      ability or exhaustion and suffocation (49.1%) due to unknown reasons were the
      most common causes of submersion injury among all patients. Most complications
      were due to aspiration pneumonia and hypoxic ischemic encephalopathy (HIE).
      Thirty-nine patients (70.9%) were followed in the ED, while 16 patients (29.1%)
      were admitted to the pediatric intensive care unit (PICU); 11 patients (20.0%)
      died. All of the risk factors of drowning should be taken into account when
      designing preventive measures and family education. In addition, all
      pediatricians should be trained periodically about the complications of
      submersion and the treatment strategies, particularly in coastal cities and areas
      where drownings occur frequently.

PMID- 24577982
TI  - Anesthesia for percutaneous transcatheter closure of atrial and ventricular
      septal defects in pediatric patients.
AB  - We aimed to investigate the anesthetic management of percutaneous closure of
      atrial and ventricular septal defects (ASD/VSD) in pediatric patients. A
      retrospective review of the anesthetic data of 351 patients who underwent
      transcatheter closure of ASD/VSD was conducted. The mean age was 8.42 +/- 5.71
      years (4 months-18 years). VSD closure was performed in 52 patients and the
      remaining 299 had a procedure for ASD closure. All patients were premedicated
      with midazolam. All procedures were performed under general anesthesia in the
      catheterization laboratory. After anesthesia induction with sevoflurane or
      intravenous anesthetics, all patients were intubated. The procedure was completed
      without any complications in 98.3% of patients. Many anesthetic drugs have been
      used for pediatric cardiac catheterization, but it cannot be concluded whether
      there is an ideal anesthetic method. Regardless of the method, the
      anesthesiologist must consider not only the need for adequate analgesia and
      immobility but also that for hemodynamic stability during the procedure. 

PMID- 24577983
TI  - Cobalamin C defect: a patient of late-onset type with homozygous p.R132*
      mutation.
AB  - Methylmalonic aciduria and homocystinuria, cobalamin C (cblC) type, is the most
      frequent inborn error of vitamin B12metabolism. The clinical phenotype includes
      systemic symptoms and neurological decompensation. Affected patients can be
      divided into two broad groups, as early-onset and late-onset. We present a
      Turkish patient who had neurological impairment at the age of four years as
      presented with late-onset cblC defect. Homozygous c.394C<T; p.R132* mutation in
      the MMACHC gene was detected. The patient was treated with hydroxocobalamin,
      betaine and folic acid combination with good clinical and biochemical response. 

PMID- 24577984
TI  - Chronic kidney disease in an adolescent with hyperuricemia: familial juvenile
      hyperuricemic nephropathy.
AB  - Chronic kidney disease (CKD) is a life-long condition associated with substantial
      morbidity and premature death due to complications from a progressive decrease in
      kidney function. Especially in children, early diagnosis and detection of the
      etiologic factors are important to improve their health outcomes. Familial
      juvenile hyperuricemic nephropathy (FJHN) is a rare autosomal-dominant disorder
      characterized by hyperuricemia with renal uric acid under-excretion and CKD.
      Genetic studies have revealed mutations in the uromodulin (UMOD) gene.
      Highlighting the importance of CKD in children, a 14-year-old girl with the rare
      diagnosis of FJHN is reported herein. 

PMID- 24577985
TI  - A case report of successful relactation.
AB  - Exclusive breastfeeding is recommended from birth until the first six months and
      then with complementary feeding up to age two. In our country, only 41.6% of
      infants are exclusively breastfed during the first six months, and the average
      duration of breastfeeding is 16 months.The term 'relactation' is used for the
      resumption of breastfeeding in infants who were not breastfed before or who quit
      suckling due to an illness of the mother or infant, breast problems, rejection of
      suckling by the infant, insufficient milk production, the mother's change of mind
      about breastfeeding, or adoption.Relactation is a laborious process that requires
      motivation and trained personnel. In our case, the process of achieving
      successful relactation in an eight-week-old infant who had not been breastfed
      before is described. The infant's young age and mother's strong motivation led to
      the success in relactation in this case. 

PMID- 24577986
TI  - Severe childhood amitriptyline intoxication and plasmapheresis: a case report.
AB  - Tricyclic antidepressant intoxication is one of the most frequently encountered
      and life-threatening causes of intoxication among referrals to emergency
      departments due to drug intoxication. There is no known antidote against any of
      the tricyclic antidepressants. The American Society for Apheresis (ASFA)
      recommends plasmapheresis to support primary treatment in this type of drug
      poisoning, which does not respond to certain and traditional treatments. We
      present a 15-year-old girl who ingested amitriptyline with suicidal intent. On
      admission, she was in a comatose state (Glasgow Coma Scale score: 5), with no
      spontaneous respiration and presence of pathological reflexes. Due to the intake
      history of lethal doses and the severe clinical picture, plasmapheresis was
      performed. She was discharged on her fifth day of hospitalization.Due to the high
      plasma protein binding property of amitriptyline, plasma exchange therapy should
      be considered in cases of severe amitriptyline intoxication as a life-saving
      therapeutic modality. 

PMID- 24577987
TI  - Thermal pillow: an unusual causative agent of erythema ab igne.
AB  - Erythema ab igne (EAI), also known as "toasted skin syndrome" or "heatinduced
      circumscribed dermal melanosis", presents with pigmented reticular skin lesions
      with telangiectasias due to prolonged thermal radiation exposure. This article
      describes a 16-year-old male patient with EAI due to the use of a thermal pillow,
      and discusses a potential causative agent of EAI. The potential hazards of
      misusing new technological equipment and the importance of consumer education are
      also discussed. 

PMID- 24577988
TI  - The first case of Bruck syndrome associated with gastroschisis.
AB  - Bruck syndrome is an extremely rare disorder featuring the unusual combination of
      skeletal changes resembling osteogenesis imperfecta with congenital contractures
      of large joints. Although the genotypic and phenotypic features of Bruck syndrome
      are heterogeneous, we report a baby girl having gastroschisis complicated with
      jejunal perforation in addition to bone fractures and joint contractures, which
      supported the diagnosis of Bruck syndrome. After surgical procedures for
      gastroschisis, the fractures were treated with splints, and cyclic pamidronate
      treatment was started. On postoperative day 30, the patient was discharged
      without any complications. She is now seven months of age, gaining weight and has
      had no additional fractures with the ongoing pamidronate treatment. Although
      prematurity and low birth weight are common in gastroschisis, musculoskeletal
      anomalies have not been reported until now, and thus the case is unique.
      Additionally, cyclic pamidronate administration is a good treatment choice for
      bone fragility in Bruck syndrome to reduce the number of fractures, and it may be
      beneficial for the subsequent clinical deterioration of the patients. 

PMID- 24577989
TI  - Ascites and abdominal pseudocyst: two uncommon ventriculoperitoneal shunt
      complications in two cases.
AB  - Ascites and abdominal pseudocysts (APC) are two rare complications that can occur
      following placement of a ventriculoperitoneal (VP) shunt. Both complications are
      characterized by abnormal intraperitoneal cerebrospinal fluid (CSF) collections.
      Although various factors have been implicated, the exact pathogenesis of the two
      conditions remains elusive. This paper presents two cases of VP shunt placement
      resulting from hydrocephaly. The first patient presented with generalized ascites
      and the other with APC, both of whom were six years old. APC and ascites after VP
      shunt placement are rare and distinct conditions; therefore, they may require
      different management strategies.

PMID- 24577990
TI  - Torsion of an epididymal cyst: a case report and review of the literature.
AB  - Torsion of an epididymal cyst (EC) on its pedicle is an extremely rare condition
      that resembles acute testicular torsion. Herein, a boy with EC torsion managed
      surgically is presented and discussed in light of the relevant literature. The
      presented child is probably the fourth case of pediatric EC torsion, and to our
      knowledge, the first report of a child who was known to have EC and was followed
      conservatively until the occurrence of EC torsion. 

PMID- 24577991
TI  - An extremely rare complication of congenital heart surgery: interventricular
      septal hematoma.
AB  - We report a rare case of interventricular septal hematoma after patch closure of
      a perimembranous ventricular septal defect in a 10-month-old infant.
      Intraoperative transesophageal echocardiography was not performed. Routine
      transthoracic echocardiography at the 1st postoperative hour showed a huge
      intramural hematoma causing severe thickening of the ventricular septum. The
      patient's hemodynamics were stable and surgical revision was not required. The
      patient recovered well without complication. 

PMID- 24577992
TI  - Scrotal pearl is not always a sign of anorectal malformation: median raphe cyst.
AB  - Pearls of meconium can be seen on the raphe of the scrotum and are considered as
      a sign of anorectal malformation (ARM). Scrotal pearls without ARM are rare in
      children and designated as median raphe cyst of the scrotum (MRC). A six-month
      old boy with scrotal pearls without ARM is presented to discuss the clinical
      features and treatment modalities of MRC in infants. 

PMID- 24577993
TI  - Hemolytic uremic syndrome outbreak in Turkey in 2011.

PMID- 24577994
TI  - Hemolytic uremic syndrome outbreak in Turkey in 2011 - Reply.

PMID- 24577995
TI  - Experiencing core symptoms of anxiety and unipolar mood disorders in late
      adolescence predicts disorder onset in early adulthood.
AB  - BACKGROUND: Identification of youth at risk for anxiety and unipolar mood
      disorders (UMDs) can improve public health by targeting those who may warrant
      early or preventive intervention. This study examined whether endorsing core
      features of anxiety and UMDs predicted onset of later anxiety and UMDs across the
      next 7-9 years, and whether having subthreshold or subclinical manifestations of
      these disorders similarly predicted onset. METHODS: Data from this study come
      from the Youth Emotion Project (YEP), a two-site investigation of common and
      specific risk factors for emotional disorders. Endorsement of core features of a
      disorder and subclinical or subthreshold anxiety and UMD diagnoses were
      determined using data from the Structured Clinical Interview for DSM-IV (SCID) at
      the baseline assessment. Participants completed annual SCIDs over the course of
      the next 7-9 years (depending on cohort). RESULTS: Endorsement of panic attacks,
      obsessions and/or compulsions, and depression and/or anhedonia predicted onset of
      panic disorder, obsessive compulsive disorder, and major depressive disorder,
      respectively. When including all anxiety disorders in a model, only the presence
      of panic attacks uniquely predicted anxiety disorder onset. The presence of
      subclinical or subthreshold panic disorder, obsessive compulsive disorder, and
      social phobia at baseline predicted the full onset of these disorders over the
      follow-up period. CONCLUSIONS: Experiencing some symptoms of anxiety and UMDs in
      the absence of meeting diagnostic criteria is indicative of risk for later onsets
      of clinically significant DSM manifestations of these disorders. These
      individuals should be identified and targeted for prevention programs.

PMID- 24577996
TI  - Delayed gadolinium-enhanced magnetic resonance imaging of medial tibiofemoral
      cartilage and its relationship with meniscal pathology: a longitudinal study
      using 3.0T magnetic resonance imaging.
AB  - OBJECTIVE: To evaluate the relationship between medial meniscal pathology and
      cartilage matrix status using delayed gadolinium-enhanced magnetic resonance
      imaging of cartilage (dGEMRIC) in medial tibiofemoral cartilage in a sample of
      middle-aged women. METHODS: A total of 148 women ages >=40 years were included,
      and 3.0T MRI of the knee was performed at baseline and at 1 year. T2-weighted,
      fat-suppressed and 3-dimensional inversion recovery-prepared spoiled gradient
      recalled echo sequences were acquired 90 minutes after gadolinium injection.
      Baseline medial meniscal pathology was scored on a scale of 0-3, where 0 =
      normal, 1 = intrasubstance meniscal signal change, 2 = single tears, and 3 =
      complex tears/maceration. The central medial femur, the medial tibial plateau,
      and the posterior medial femur were subjected to dGEMRIC at baseline and at 1
      year. Analysis of covariance was used to examine whether baseline and 1-year
      dGEMRIC indices in the same regions were related to the severity of meniscal
      damage at baseline, using normal medial menisci (grade 0) as the reference.
      RESULTS: Medial compartments with grade 3 lesions showed significantly lower
      dGEMRIC indices (less proteoglycan content) at the central medial femur region
      compared with compartments with normal menisci. Mean +/- SEM differences in
      dGEMRIC indices between grade 3 and grade 0 menisci at the central medial femur
      were -119.1 +/- 34.2 msec at baseline (P = 0.03) and -120.3 +/- 35.2 msec at
      followup (P = 0.04). CONCLUSION: High-grade damage of the medial meniscus showed
      significant associations with lower dGEMRIC indices. The dGEMRIC technique may be
      a useful tool in detecting early degenerative changes of cartilage when meniscal
      function is lost.

PMID- 24577997
TI  - Office-based vocal fold injection with the laryngeal introducer technique.
AB  - OBJECTIVES/HYPOTHESIS: There are numerous techniques for awake laryngeal
      injection, each with its limitations and technical challenges. We demonstrate a
      modification to the thyrohyoid approach for injection that stabilizes needle
      introduction and allows for consistent placement in a wide variety of larynges.
      STUDY DESIGN: Retrospective review at a tertiary care institution. METHODS: A
      retrospective review was performed of the charts for patients consecutively
      undergoing awake vocal fold injection laryngoplasty in 2013 for glottic
      insufficiency due to unilateral vocal fold paralysis, vocal fold atrophy, or
      sulcus vocalis using the laryngeal introducer technique. The consistency of
      needle placement, ease of technique, and patient tolerance was assessed. The
      technique utilizes a curved 1.5-inch 18-gauge needle as a laryngeal introducer
      through the thyroid notch. Laryngeal injection augmentation is then performed
      using a curved 3.5-inch 25-gauge spinal needle through the introducer. RESULTS:
      Twenty-one patients were identified who underwent awake vocal fold injection
      laryngoplasty for glottic insufficiency. All 21 injections were successfully
      placed. Five of seven injections attempted by resident physicians were able to be
      completed without attending assistance. Patient experience data demonstrated good
      tolerance, with a preference for the awake procedure as compared to that
      performed under general anesthesia. CONCLUSIONS: The laryngeal introducer
      technique is a novel way of performing awake laryngeal injections. It provides a
      high rate of success, the ability to be consistently performed by inexperienced
      clinicians, and is well tolerated by patients.

PMID- 24577999
TI  - Silvia Pierangeli, PhD (1955-2013).

PMID- 24578000
TI  - Quality in hemostasis and thrombosis--part III. Preface.

PMID- 24577998
TI  - An overview of famotidine polymorphs: solid-state characteristics,
      thermodynamics, polymorphic transformation and quality control.
AB  - Crystal polymorphism of pharmaceuticals has well-known profound effects on the
      physical, chemical, and pharmaceutical properties of drugs, which can result in
      changes in the solubility, stability, dissolution, bioavailability, and efficacy
      of drugs. In this review article, famotidine (FAM), which has a well-known trade
      name of Pepcid(r), was selected as a model drug. Although FAM has three
      polymorphs (forms A, B and C), forms A and B have been commonly discussed. The
      active pharmaceutical ingredient (API) in the commercial version of FAM is the
      metastable form B. FAM has been a concern of FDA because of the physical
      properties, solubilities, bioavailabilities, or bioequivalencies of the different
      polymorphic forms. In addition, a patent infringement suit of FAM polymorph had
      been made sound legal arguments in the pharmaceutical market. We review the solid
      state characteristics, thermodynamics, polymorphic transformation, and quality
      control of FAM in drug products. In particular, pharmaceutical processes, such as
      grinding, compression, and heating temperature have a significant effect on the
      polymorphic transformation of FAM. Moreover, environmental humidity and residual
      water content should be well controlled to prevent polymorphic transformation of
      FAM during pharmaceutical processing. Several thermal and spectroscopic
      analytical techniques used for qualitative and quantitative determinations of
      polymorphic transformation of FAM after different treatments or quality control
      of FAM in the commercial tablets before and after the expiration dates have been
      discussed.

PMID- 24578001
TI  - Nickel-catalyzed synthesis of N-aryl-1,2-dihydropyridines by [2+2+2]
      cycloaddition of imines with alkynes through T-shaped 14-electron aza
      nickelacycle key intermediates.
AB  - Despite there being a straightforward approach for the synthesis of 1,2
      dihydropyridines, the transition-metal-catalyzed [2+2+2] cycloaddition reaction
      of imines with alkynes has been achieved only with imines containing an N
      sulfonyl or -pyridyl group. Considering the importance of 1,2-dihydropyridines as
      useful intermediates in the preparation of a wide range of valuable organic
      molecules, it would be very worthwhile to provide novel strategies to expand the
      scope of imines. Herein we report a successful expansion of the scope of imines
      in nickel-catalyzed [2+2+2] cycloaddition reactions with alkynes. In the presence
      of a nickel(0)/PCy3 catalyst, a reaction with N-benzylidene-P,P
      diphenylphosphinic amide was developed. Moreover, an application of N-aryl imines
      to the reaction was also achieved by adopting N-heterocyclic carbene ligands. The
      isolation of an (eta(2)-N-aryl imine)nickel(0) complex containing a 14-electron
      nickel(0) center and a T-shaped 14-electron five-membered aza-nickelacycle is
      shown. These would be considered as key intermediates of the reaction. The
      structure of these complexes was unambiguously determined by NMR spectroscopy and
      X-ray analyses.

PMID- 24578005
TI  - Editorial.

PMID- 24578003
TI  - Is there a relation between triglyceride concentrations in very low density
      lipoprotein and the index of insulin resistance in nondiabetic subjects?
AB  - BACKGROUND: Serum very low density lipoprotein (VLDL) levels increase during the
      early stages of insulin resistance; therefore, determination of VLDL levels would
      be useful for evaluating the progression of metabolic syndrome and diabetes
      mellitus. The aim of this study was to clarify the clinical utility of
      triglyceride in VLDL (VLDL-TG) level, determined using a homogeneous assay kit
      (Shino-test Corporation, Tokyo, Japan), as an index of insulin resistance.
      METHODS: We enrolled 74 subjects in this study (diabetic subjects, n = 42;
      nondiabetic subjects, n = 32). The levels of VLDL-TG, remnant-like lipoprotein
      particle cholesterol, preheparin lipoprotein lipase mass, and other biochemical
      markers were determined. RESULTS: VLDL-TG levels were significantly higher in the
      diabetic group (1.04 +/- 0.84 mmol/l vs. 0.64 +/- 0.42 mmol/l, P < 0.01) than in
      the nondiabetic group. In the nondiabetic group, VLDL-TG was significantly
      correlated with the homeostasis model assessment of insulin resistance (HOMA-IR),
      the index for insulin resistance (r = 0.513, P = 0.003). VLDL-TG levels, but not
      TG levels, were higher in the highest quartile (HOMA-IR) of the nondiabetic
      group. CONCLUSION: VLDL-TG level was a useful early marker for insulin
      resistance, especially in nondiabetic subjects. The homogeneous VLDL-TG assay is
      a simple, low-cost method for determining insulin resistance.

PMID- 24578002
TI  - In-depth comparative characterization of hemoglobin glycation in normal and
      diabetic bloods by LC-MSMS.
AB  - The glycation level at beta-Val-1 of the hemoglobin beta chain in human blood
      (HbA1c%) is used to diagnose diabetes and other diseases. However, hemoglobin
      glycation occurs on multiple sites on different isoforms with different kinetics,
      but its differential profile has not been clearly demonstrated. In this study,
      hemoglobin was extracted from the blood of normal and diabetic individuals by
      protein precipitation. Triplicate solutions prepared from each sample were
      directly analyzed or digested with multiple enzymes and then analyzed by nano
      LC/MS via bottom-up approach for side-by-side characterization. Intact hemoglobin
      analysis indicated a single glucose-dominant glycation, which showed good
      correlation with the HbA1c% values. Moreover, full sequence (100%) of alpha/beta
      globin was mapped and seven glycation sites were unambiguously assigned. In
      addition to beta-Val-1, two other major sites at alpha-Lys-61 and beta-Lys-66,
      which contain the common sequence HGKK, and four minor sites (<1%) on alpha-Val
      1, beta-Lys-132, alpha-Lys-127, and alpha-Lys-40 were identified. All sites were
      shown to exhibit similar patterns of site distribution despite different glucose
      levels. Both the intact mass measurement and bottom-up data consistently
      indicated that the total glycation percentage of the beta-globin was twice higher
      than the alpha-globin. Using molecular modeling, the 3D structure of the
      consensus sequence (HGKK) was shown to contain a phosphate triangle cavity, which
      helps to catalyze the glycation reaction. For the first time, hemoglobin
      glycation in normal and diabetic bloods was comparatively characterized in-depth
      with 100% sequence coverage. The results provide insight about the HbA1c
      parameter and help define the new and old markers.

PMID- 24578006
TI  - Clinical significance of abdominal scintigraphy using (99m)Tc-HMPAO-labelled
      leucocytes in patients with seronegative spondyloarthropathies.
AB  - Abdominal scintigraphy shows silent gut inflammation in patients with
      spondyloarthropathies (Sp) without clinical evidence of gut inflammation.
      Abdominal scintigraphy images are different than those obtained in patients with
      ulcerative colitis or Crohn's disease and are not related to the anti
      inflammatory drugs administered. The aim of this study was to examine the
      clinical associations of findings on abdominal scintigraphy in patients with Sp.
      A total of 204 Sp patients (European Spondylarthropathy Study Group 1991
      criteria) and 54 non-Sp controls receiving non-steroidal anti-inflammatory drugs
      were studied. Abdominal scintigraphy images were obtained at 30 and 120 min after
      injection of technetium-99m hexamethylpropylene amine oxime ((99m)Tc-HMPAO)
      labelled leucocytes. (99m)Tc-HMPAO-labelled leucocyte scans were positive in 104
      Sp patients (50.9%) and in six non-Sp controls (2.9%) (P<0.001; OR=8.32; 95%
      CI=3.23-22.67). Silent gut inflammation was not associated with any of the
      following: age of onset, duration of evolution, sex, family history of Sp or
      psoriasis, articular manifestations, extra-articular manifestations, radiological
      findings or HLA-B27 positivity. Positive abdominal scintigraphy was associated
      with active disease (P<0.0001; OR=52.7; 95% CI=19-145.6) and an increase in the C
      reactive protein (P<0.005; OR=3.4; 95% CI=1.5-7.4). It is concluded that (a)
      abdominal scintigraphy using (99m)Tc-HMPAO-labelled leucocytes is of value in
      detecting the silent gut inflammation in Sp patients, and (b) silent gut
      inflammation is related to the clinical activity, but is not associated with any
      particular type of illness or with HLA-B27. 

PMID- 24578007
TI  - Correlation of Glut-1 glucose transporter expression with [(18)F]FDG uptake in
      non-small cell lung cancer.
AB  - Positron emission tomography (PET) with [(18)F]2-fluoro-2-deoxy-D-glucose (FDG)
      may show negative results for bronchioloalveolar lung carcinoma. We investigated
      the correlation of Glut-1 glucose transporter expression with [(18)F]FDG uptake
      in non-small cell lung cancer. Thirty-two patients with 34 non-small cell lung
      cancers (7 bronchioloalveolar carcinomas, 23 non-bronchioloalveolar
      adenocarcinomas, 3 squamous cell carcinomas, and 1 adenosquamous cell carcinoma)
      were studied. Final diagnoses were established by histology (via thoracotomy) in
      all patients. [(18)F]FDG PET was performed 40 min after i.v. injection of 185 MBq
      [(18)F]FDG. For semi-quantitative analysis of [(18)F]FDG uptake, standardized
      uptake values (SUVs) were calculated. Glut-1 expression was studied in terms of
      the immunohistochemistry of paraffin sections using anti-Glut-1 antibody to
      determine the intensity (0-3) of Glut-1 immunoreactivity and percentage of the
      Glut-1-positive area. Of seven bronchioloalveolar carcinomas, six (85.7%) were
      negative for the expression of Glut-1, while only one (4.3%) of 23 non
      bronchioloalveolar adenocarcinomas was negative (P<0.0001). The percentages of
      Glut-1-positive area, as well as the SUVs, were significantly lower in
      bronchioloalveolar carcinomas (n=7) (2.86%+/-7.56% and 1.25+/-0.75, respectively)
      than in non-bronchioloalveolar adenocarcinomas (n=23) (54.83%+/-25.64%, P<0.0001,
      and 3.94+/-1.93, P=0.001, respectively). The degree of cell differentiation
      correlated with the percentage of Glut-1-positive area and SUVs in adenocarcinoma
      of the lung. Correlations between SUVs and the intensity of Glut-1
      immunoreactivity were also significant (intensities 0 and 1, n=11, SUV 1.47+/
      0.63; intensities 2 and 3, n=23, SUV 4.78+/-2.13; P<0.0001). The percentage of
      Glut-1-positive area correlated significantly with SUVs (n=34, r=0.658, P<0.01).
      Overexpression of Glut-1 correlated with high [(18)F]FDG uptake. These findings
      suggest that Glut-1 expression is related to [(18)F]FDG uptake in non-small cell
      lung cancer. Glut-1 expression, as well as [(18)F]FDG uptake, correlated with the
      degree of cell differentiation in adenocarcinomas, and both Glut-1 expression and
      [(18)F]FDG uptake were significantly lower in bronchioloalveolar carcinomas than
      in non-bronchioloalveolar carcinomas. 

PMID- 24578008
TI  - Comparative (99m)Tc-MIBI, (99m)Tc-tetrofosmin and (99m)Tc-furifosmin uptake in
      human soft tissue sarcoma cell lines.
AB  - The uptake characteristics of technetium-99m hexakis-2-methoxyisobutylisonitrile
      (MIBI), (99m)Tc-tetrofosmin and (99m)Tc-furifosmin in human soft tissue sarcoma
      cell lines were investigated and compared. After 10-120 min of incubation at 37
      degrees C, 32 degrees C and 22 degrees C with (99m)Tc-MIBI, (99m)Tc-tetrofosmin
      and (99m)Tc-furifosmin, the kinetics of cellular uptake of these tracers in human
      soft tissue sarcoma cells SW 684 (fibrosarcoma), SW 872 (liposarcoma), SW 982
      (synovial sarcoma) and SW 1353 (chondrosarcoma) was assessed. The uptake of
      (99m)Tc-MIBI, (99m)Tc-tetrofosmin and (99m)Tc-furifosmin was temperature
      dependent. The kinetics of uptake of (99m)Tc-MIBI and of (99m)Tc-tetrofosmin was
      similar between fibrosarcoma and liposarcoma cells, as well as between synovial
      sarcoma and chondrosarcoma cells. (99m)Tc-furifosmin showed similar uptake
      kinetics in all cell lines. The uptake of (99m)Tc-furifosmin was, however,
      significantly higher in liposarcoma than in the other cells. The data indicate
      that the cellular uptake of (99m)Tc-MIBI, (99m)Tc-tetrofosmin and (99m)Tc
      furifosmin is dependent on cellular metabolic activity. 

PMID- 24578010
TI  - Erratum to: Gated SPET quantification of small hearts: mathematical simulation
      and clinical application.

PMID- 24578009
TI  - Concerns about (99m)Tc-labelled ciprofloxacin for infection detection.

PMID- 24578011
TI  - Erratum to: Kinetics of 3-[(123)I]iodo-L-alpha-methyltyrosine transport in rat C6
      glioma cells.

PMID- 24578012
TI  - HIV risk and prevention behaviors in men who have sex with men and women: a
      respondent-driven sampling study in Shenzhen, China.
AB  - Men who have sex with men and women (MSMW) may expand the HIV epidemic from men
      who have sex with men to the female population. From a respondent-driven sampling
      survey in Shenzhen, China, we quantified the burden of HIV/syphilis and studied
      patterns of risk and prevention behaviors in 107 MSMW, and compared these with
      those of 542 men who have sex with men only (MSM-only). HIV prevention behaviors
      and consistent condom use with male partners did not differ between the two
      groups. However, HIV risk behaviors were more common among MSMW than MSM-only.
      Moreover, among MSMW, the HIV prevalence was as high as 6 % and consistent condom
      use was extremely low with female partners in MSMW. We conclude that there is
      risk of HIV transmission from MSMW to the female population. Special efforts are
      needed to convince MSMW they should refrain from HIV risk behaviors.

PMID- 24578013
TI  - Effect of simulated pulpal fluid circulation on intrapulpal temperature following
      irradiation with an Nd:YVO4 laser.
AB  - It is suggested that pulpal fluid circulation has an impact on pulp temperature
      increase during heat-generating dental treatment procedures. Thus, the aim of the
      study was to assess the effect of a simulated pulpal fluid circulation on
      temperature changes inside the pulp chamber following laser irradiation of the
      tooth surface. Twenty freshly extracted human multirooted teeth were included and
      cross-sectioned along the long axis exposing two root canals each. The pulp
      chamber and root canals were cleaned from remaining soft tissues to achieve
      access for a temperature sensor and two cannulas to allow fluid circulation.
      Cross sections were glued together, and the roots were encased with silicone
      impression material to ensure the position of the connected devices. Each tooth
      was irradiated by employing a neodymium-doped yttrium orthovanadate (Nd:YVO4)
      laser at 1,064 nm with a pulse duration of 9 ps and a repetition rate of 500 kHz.
      A commercially available scanning system (SCANcube 7, SCANLAB) deflected the beam
      by providing rectangular irradiated areas of 0.5 mm edge length. Measurements
      were performed with four different settings for fluid circulation: without any
      water and with water (23  degrees C) at a flow rate of 6, 3, and 0 ml/min. The
      primary outcome measure was the maximum temperature difference (DeltaT) after
      laser irradiation. Highest temperature changes (median 3.6 K, range 0.5-7.1 K)
      could be observed without any fluid inside the pulp chamber. Water without
      circulation decreased DeltaT values statistically significantly (median 1.4 K,
      range 0.2-4.9 K) (p < 0.05). Lowest temperature changes could be observed with a
      water flow rate of 6 ml/min (median 0.8 K, range 0.2-3.7 K) (p < 0.05). Pulpal
      fluid circulation has a cooling effect on temperature increase caused by laser
      irradiation of dental hard tissues. Studies on heat generation during dental
      treatment procedures should include this aspect to assess a potential thermal
      injury of pulp tissue.

PMID- 24578014
TI  - Complete response to induction therapy in patients with Myc-positive and double
      hit non-Hodgkin lymphoma is associated with prolonged progression-free survival.
AB  - BACKGROUND: Myc-positive B-cell non-Hodgkin lymphoma (NHL) with or without a B
      cell chronic lymphocytic leukemia/lymphoma 2 (BCL2) rearrangement is associated
      with inferior progression-free survival (PFS) and overall survival (OS). In this
      study, the authors reviewed the outcomes of patients with myc-positive and double
      hit NHL at The Ohio State University. METHODS: All patients who had non-Burkitt,
      aggressive B-cell NHL from 2008 to 2011 were assessed for the t(14;18)
      translocation and for v-myc avian myelocytomatosis viral oncogene homolog (CMYC)
      rearrangements at diagnosis, and all myc-positive patients were included in the
      current analysis. Associations with clinical characteristics were described, and
      univariable and multivariable models were used to assess correlations between
      clinical variables and outcomes. RESULTS: Of 49 myc-positive patients, 29
      patients also had BCL2 rearrangements (double-hit NHL). No patients underwent
      autologous stem cell transplantation in first remission. For all myc-positive
      patients, the median PFS was 16.6 months, and the median OS was 37.7 months. For
      patients who had double-hit NHL, the median PFS was 8 months, and the median OS
      was 12.5 months; whereas the median PFS and OS were not reached for myc-positive
      patients. A complete response (CR) after front-line therapy, the presence of
      t(14;18), International Prognostic Index (IPI) group, and age were associated
      with PFS; whereas only the achievement of a CR and age >60 years were associated
      with OS in the multivariable setting. The median PFS was 3.3 months, and the
      median and OS was 7.0 months for patients who did not attain a CR; and the
      medians were not reached for patients who achieved a CR (P < .00001).
      CONCLUSIONS: The achievement of a CR with front-line therapy is associated with a
      prolonged PFS and OS in patients with myc-positive NHL, even after adjusting for
      type of initial therapy, histology, age, IPI, or the presence of a concurrent
      BCL2 translocation.

PMID- 24578015
TI  - Role for T-type Ca2+ channels in sleep waves.
AB  - Since their discovery more than 30 years ago, low-threshold T-type Ca(2+)
      channels (T channels) have been suggested to play a key role in many EEG waves of
      non-REM sleep, which has remained exclusively linked to the ability of these
      channels to generate low-threshold Ca(2+) potentials and associated high
      frequency bursts of action potentials. Our present understanding of the
      biophysics and physiology of T channels, however, highlights a much more diverse
      and complex picture of the pivotal contributions that they make to different
      sleep rhythms. In particular, recent experimental evidence has conclusively
      demonstrated the essential contribution of thalamic T channels to the expression
      of slow waves of natural sleep and the key role played by Ca(2+) entry through
      these channels in the activation or modulation of other voltage-dependent
      channels that are important for the generation of both slow waves and sleep
      spindles. However, the precise contribution to sleep rhythms of T channels in
      cortical neurons and other sleep-controlling neuronal networks remains unknown,
      and a full understanding of the cellular and network mechanisms of sleep delta
      waves is still lacking. 

PMID- 24578016
TI  - Looking under the hood of the dot-probe task: an fMRI study in anxious youth.
AB  - BACKGROUND: Anxious youth have shown altered behavioral performance on the dot
      probe task, but neural activation patterns provoked by the task remain poorly
      understood. In particular, neural mechanisms of threat disengagement, a
      clinically relevant construct, have been inadequately explored. METHOD: During
      fMRI acquisition, 121 youth (ages 9-13; 90 with Generalized Anxiety Disorder,
      Separation Anxiety Disorder, and/or Social Phobia; 31 nonanxious controls)
      completed a dot-probe task, which required participants to identify the location
      of a dot replacing either a neutral or fearful face in a pair containing both
      faces. We assessed neural substrates of threat disengagement by comparing
      congruent trials (in which the dot replaces the fearful face) to incongruent
      trials (in which the dot replaces the neutral face). RESULTS: Across subjects,
      decreased rostrodorsal anterior cingulate cortex (rdACC) activity was observed
      specifically during incongruent trials. Nonanxious youth showed a convergent
      pattern in bilateral parahippocampal and hippocampal regions, whereas anxious
      youth showed an opposing pattern in these limbic areas, suggesting less
      integration of response across cortical and limbic areas relevant to threat
      appraisal. Reduced functional connectivity between rdACC and left
      parahippocampus/hippocampus was associated with greater anxiety. CONCLUSIONS: In
      the largest dot-probe fMRI sample to date, both anxious and nonanxious youth
      showed a neural pattern consistent with successful disengagement of threat
      reactivity in the rdACC. However, anxious youth showed evidence of abnormal
      disengagement in bilateral parahippocampal/hippocampal clusters when attention
      was directed away from threat. Early interventions targeting neural mechanisms of
      threat disengagement may be beneficial, for example, by increasing integration
      across rdACC and limbic regions.

PMID- 24578017
TI  - Newborn screening for SCID in New York State: experience from the first two
      years.
AB  - PURPOSE: To describe the process and assess outcomes for the first 2 years of
      newborn screening for severe combined immunodeficiency (SCID NBS) in New York
      State (NYS). METHODS: The NYS algorithm utilizes a first-tier molecular screen
      for TRECs (T-cell receptor excision circles), the absence of which is indicative
      of increased risk of immunodeficiency. RESULTS: During the first 2 years, 485,912
      infants were screened for SCID. Repeat specimens were requested from 561
      premature and 746 non-premature infants with low or borderline TRECs. A total of
      531 infants were referred for diagnostic evaluation leading to identification of
      10 infants with SCID and 87 with a clinically significant non-SCID abnormality
      based on flow cytometry or CBC results (positive predictive value 20.3 %). Nine
      infants were diagnosed with typical SCID and one with leaky SCID. SCID diagnoses
      included two patients with adenosine deaminase deficiency, three patients with
      typical and one with leaky IL2RG-related SCID, one patient with IL7Ralpha-related
      SCID, and three cases of typical SCID, etiology unknown. TRECs were undetectable
      in eight of the nine babies with typical SCID. Infants with other non-SCID
      conditions included 27 patients with a syndrome that included T-cell impairment,
      18 of which had DiGeorge syndrome. Seventeen infants had T-cell impairment
      secondary to another clinically significant condition, and 13 were classified as
      'other'. Among 30 infants classified as idiopathic T-cell lymphopenia, 11 have
      since resolved, and the remainder continues to be followed. One infant with
      undetectable TRECs had normal follow-up studies. Molecular studies revealed the
      presence of two changes in the infant's DNA. CONCLUSIONS: Overall, ten infants
      with SCID were identified during the first 2 years of screening in NYS, yielding
      an incidence of approximately 1 in 48,500 live births, which is consistent with
      the incidence observed by other states screening for SCID. The incidence of any
      clinically significant laboratory abnormality was approximately 1 in 5,000; both
      estimates are higher than estimates prior to the onset of newborn screening for
      SCID. Improvements to the NYS algorithm included the addition of a borderline
      category that reduced the proportion of infants referred for flow cytometric
      analysis, without decreasing sensitivity. We identified a large number of infants
      with abnormal TRECs and subsequent idiopathic T-cell lymphopenia. Long-term
      follow-up studies are needed to determine the prognosis and optimal treatment for
      this group of patients, some of whom may present with previously unrecognized,
      transient lymphopenia of infancy.

PMID- 24578019
TI  - Editorial.

PMID- 24578020
TI  - Plane down in the city: Operation Crash and Surge.
AB  - This article is about the experiences gained from the largest full-scale exercise
      ever conducted in the State of Florida, specifically regarding the Orlando
      International Airport (MCO) venues. The exercise was centred on an airplane
      crashing into a hotel just outside of MCO property. The scenario clarified
      details regarding Incident Command and the unique jurisdictional responsibilities
      associated with a large-scale mass casualty incident. There were additional
      challenges with airline operations, walking wounded, and information sharing that
      provided valuable experiences toward enhancing emergency operations. This article
      also outlines information gained by the MCO "go team" that traveled to San
      Francisco following the crash of Asiana flight 214. This real-life incident shone
      a light on many of the strengths and opportunities found throughout the MCO
      exercise and this article shows the interrelationship of both of these invaluable
      experiences. 

PMID- 24578021
TI  - Community resiliency through recovery resource supply chain planning.
AB  - Information in this paper is the result of recommendations and remedies developed
      at 'Local Supply Chain Capacity in a Crisis Summit Exercise' held in Arlington,
      VA on 30th-31st January,2013. At the event, which was funded through the Regional
      Catastrophic Preparedness Grant Program, national private sector and not-for
      profit essential resource provider experts in sectors such as transportation,
      communication systems, energy/power, financial resources, medical supplies and
      other vital supplies, together with emergency managers, discussed best practices,
      major challenges and exchanged remedy recommendations. 

PMID- 24578022
TI  - Public-private partnership from theory to practice: Walgreens and the Boston
      Public Health Commission supporting each other before and after the Boston
      bombings.
AB  - This paper presents an overview of the public health and medical services
      continuity of operations, response and recovery efforts in the aftermath of the
      Boston bombings. Countless public and private organisations and agencies came
      together to support the community and the survivors. The efforts of these
      organisations define what it means to be Boston Strong. 

PMID- 24578023
TI  - Business continuity management in international organisations.
AB  - In the area of business continuity management, a preliminary review of the
      literature reveals extensive knowledge, expertise and experience concerning
      organisations in the private and public sectors. It is interesting to note,
      however, that there is little literature about business continuity management in
      international organisations, although these entities are complex and particularly
      prone to threats. This apparent absence of literature suggests that business
      continuity management has not yet hit the agenda of international organisations.
      In recent years, member states have encouraged senior management to design and
      implement business continuity strategies to minimise the mishandling of an
      internal crisis and build organisational resilience, but very few of them have
      actually been able to design and implement comprehensive business continuity
      programmes. Based on actual experience working in international organisations,
      this paper outlines some of the challenges faced by international organisations
      in developing and implementing business continuity activities and attempts to
      make suggestions for further improvement. 

PMID- 24578018
TI  - Postnatal inflammation in the pathogenesis of bronchopulmonary dysplasia.
AB  - Exposure to hyperoxia, invasive mechanical ventilation, and systemic/local sepsis
      are important antecedents of postnatal inflammation in the pathogenesis of
      bronchopulmonary dysplasia (BPD). This review will summarize information obtained
      from animal (baboon, lamb/sheep, rat and mouse) models that pertain to the
      specific inflammatory agents and signaling molecules that predispose a premature
      infant to BPD.

PMID- 24578025
TI  - Three steps to safety: developing procedures for active shooters.
AB  - Every Second counts once gunshots are heard in the workplace environment. Close
      the office door, turn out the lights and turn the mobile phone to 'silent' is the
      standard mantra for what is expected in the response efforts; however, is that
      enough? In a perfect world, this sermon may fall short of what emergency
      management practitioners might preach as it does not adequately fulfil the
      reality of what is best practice for optimal life safety. This paper offers
      options for lockdown preparedness and response to address internal lockdown from
      the moment shots are fired. Recommendations for the creation of a lockdown plan,
      building assessment surveys and a controlled, simulated exercise are addressed to
      raise awareness in response methods and reduce overall response time. The
      procedures suggested in this paper will optimise training efforts using the
      community's standard emergency operating procedures in response to workplace
      violence to minimise loss of life. 

PMID- 24578024
TI  - Application impact analysis: a risk-based approach to business continuity and
      disaster recovery.
AB  - There are many possible disruptions that can occur in business. Overlooking or
      under planning for Business Continuity requires time, understanding and careful
      planning. Business Continuity Management is far more than producing a document
      and declaring business continuity success. What is the recipe for businesses to
      achieve continuity management success? Application Impact Analysis is a method
      for understanding the unique Business Attributes. This AIA Cycle involves a risk
      based approach to understanding the business priority and considering business
      aspects such as Financial, Operational, Service Structure, Contractual Legal, and
      Brand. The output of this analysis provides a construct for viewing data,
      evaluating impact, and delivering results, for an approved valuation of Recovery
      Time Objectives (RTO). 

PMID- 24578026
TI  - Lessons learned in crisis management.
AB  - This paper will explore lessons learned following a series of natural and man
      made disasters affecting the Massachusetts Mutual Life Insurance Company and/or
      its subsidiaries. The company employs a team of certified continuity
      professionals who are charged with overseeing resilience on behalf of the
      enterprise and leading recovery activities wherever and whenever necessary. 

PMID- 24578027
TI  - Whole community planning: building resiliency at the local level.
AB  - Business continuity planning often looks to preserving internal operations and
      focuses on customer retention as a marker for a successful outcome after a
      disaster. Building more resilient continuity plans also means planning for the
      survival of the community at large. As the national emphasis in the USA on 'whole
      community planning' becomes prominent guidance for emergency management planning,
      this paper examines the implications for businesses as members of the whole
      community and how they can increase their involvement in the whole community
      process. The paper will also discuss the impediments to and benefits of becoming
      a partner in planning for the community at large. 

PMID- 24578028
TI  - Wheels, hubs and spokes: incorporating a scorecard into a business continuity
      programme.
AB  - A scorecard can provide much more than periodic measurements; it can actually
      serve as the 'hub' of a programme. By taking a strategic look at what one is
      trying to accomplish, using consistent messaging, following a flexible but
      defined process and creating an actionable report for the senior leadership, a
      programme can be built that not only gets attention but is also efficient and
      effective. The scorecard establishes accountability and consistency while
      creating a brand for a business continuity programme. 

PMID- 24578029
TI  - How well do men's faces and voices index mate quality and dominance?
AB  - Previous studies have used self-ratings or strangers' ratings to assess men's
      attractiveness and dominance, attributes that have likely affected men's access
      to mates throughout human evolution. However, attractiveness and dominance
      include more than isolated impressions; they incorporate knowledge gained through
      social interaction. We tested whether dominance and attractiveness assessed by
      acquaintances can be predicted from (1) strangers' ratings made from facial
      photographs and vocal clips and (2) self-ratings. Two university social
      fraternities, their socially affiliated sororities, and independent raters
      evaluated men's short- and long-term attractiveness, fighting ability, and
      leadership ability. Ratings made by unfamiliar men using faces, but not voices,
      predicted acquaintance-rated fighting and leadership ability, whereas ratings
      made by unfamiliar women from faces and voices predicted acquaintance-rated short
      and long-term attractiveness. Except for leadership, self-ratings aligned with
      peers' evaluations. These findings support the conclusion that faces and voices
      provide valuable information about dominance and mate quality.

PMID- 24578030
TI  - Rheumatoid arthritis during pregnancy and postnatal catch-up growth in the
      offspring.
AB  - OBJECTIVE: Active rheumatoid arthritis (RA) during pregnancy and the presence of
      rheumatoid factor (RF) or anti-citrullinated protein antibodies (ACPAs) are
      associated with lower birth weight of the child. Moreover, treatment of the
      mothers with prednisone may shorten the gestational age at birth. Rapid catch-up
      in weight for length during the first year of life has been related to a worse
      cardiovascular and metabolic profile in early adulthood. This study was therefore
      undertaken to assess the influence of RA disease activity, medication use, and
      presence of RF or ACPAs during pregnancy on the growth of the child in the first
      year of life. METHODS: Among 180 children born to mothers with RA, the tempo of
      catch-up in weight during the first year of life was studied. Independent
      variables were the extent of RA disease activity (according to the Disease
      Activity Score in 28 joints [DAS28]), medication use, and presence of RF or ACPAs
      during pregnancy. RESULTS: Of 167 children with available data, 52 (31%) showed
      catch-up in weight in the first year of life, of whom 90% (47 of 52) showed rapid
      catch-up. An elevated DAS28 score in the mother was associated with rapid catch
      up in weight of the offspring, independent of maternal medication use or the
      presence of RF or ACPAs during pregnancy (odds ratio 1.44 [95% confidence
      interval 1.07-1.95] per 1-point increase in the DAS28). Use of medications during
      pregnancy had no influence on postnatal growth. CONCLUSION: Elevated RA disease
      activity during pregnancy should be avoided because it is associated with rapid
      postnatal catch-up in weight, a risk factor for a worse cardiovascular and
      metabolic profile in adults. Medication for RA during pregnancy, including
      prednisone, had no effect on growth. Continuation or extension of medication will
      not only improve maternal health during pregnancy, but could be beneficial for
      the future health of the unborn child.

PMID- 24578031
TI  - The utilization of the acyl-CoA and the involvement PDAT and DGAT in the
      biosynthesis of erucic acid-rich triacylglycerols in Crambe seed oil.
AB  - The triacylglycerol of Crambe abyssinica seeds consist of 95% very long chain
      (>18 carbon) fatty acids (86% erucic acid; 22:1?13) in the sn-1 and sn-3
      positions. This would suggest that C. abyssinica triacylglycerols are not formed
      by the action of the phospholipid:diacylglycerol acyltransferase (PDAT), but are
      rather the results of acyl-CoA:diacylglycerol acyltransferase (DGAT) activity.
      However, measurements of PDAT and DGAT activities in microsomal membranes showed
      that C. abyssinica has significant PDAT activity, corresponding to about 10% of
      the DGAT activity during periods of rapid seed oil accumulation. The specific
      activity of DGAT for erucoyl-CoA had doubled at 19 days after flowering compared
      to earlier developmental stages, and was, at that stage, the preferred acyl
      donor, whereas the activities for 16:0-CoA and 18:1-CoA remained constant. This
      indicates that an expression of an isoform of DGAT with high specificity for
      erucoyl-CoA is induced at the onset of rapid erucic acid and oil accumulation in
      the C. abyssinica seeds. Analysis of the composition of the acyl-CoA pool during
      different stages of seed development showed that the percentage of erucoyl groups
      in acyl-CoA was much higher than in complex lipids at all stages of seed
      development except in the desiccation phase. These results are in accordance with
      published results showing that the rate limiting step in erucic acid accumulation
      in C. abyssinica oil is the utilization of erucoyl-CoA by the acyltransferases in
      the glycerol-3-phosphate pathway.

PMID- 24578032
TI  - A comparative study into alterations of coenzyme Q redox status in ageing pigs,
      mice, and worms.
AB  - Coenzyme Q derivatives (CoQ) are lipid soluble antioxidants that are synthesized
      endogenously in almost all species and function as an obligatory cofactor of the
      respiratory chain. There is evidence that CoQ status is altered by age in several
      species. Here we determined level and redox-state of CoQ in different age groups
      of pigs, mice and Caenorhabditis elegans. Since these species are very different
      with respect to lifespan, reproduction and physiology, our approach could provide
      some general tendencies of CoQ status in ageing organisms. We found that CoQ
      level decreases with age in pigs and mice, whereas CoQ content increases in older
      worms. As observed in all three species, ubiquinone, the oxidized form of CoQ,
      increases with age. Additionally, we were able to show that supplementation of
      ubiquinol-10, the reduced form of human CoQ10 , slightly increases lifespan of
      post-reproductive worms. In conclusion, the percentage of the oxidized form of
      CoQ increases with age indicating higher oxidative stress or rather a decreased
      anti-oxidative capacity of aged animals.

PMID- 24578036
TI  - German CABG score: a specific risk model for patients undergoing isolated
      coronary artery bypass grafting.
AB  - BACKGROUND: A specific risk model concerning mortality of patients undergoing
      isolated coronary artery bypass grafting (CABG) is developed based on the
      national quality benchmarking mandatory by law in Germany. METHODS: On the basis
      of the national data pool from 2004, a risk score model for patients undergoing
      isolated CABG was developed and finally adjusted with the data of 43,145 patients
      of the year 2008. Modeling was performed by logistic regression analysis. This
      risk model was validated with the 2007 data pool which comprised 45,569 patients.
      RESULTS: Observed in-hospital mortality after isolated CABG procedures was 3.0%
      in 2008. Hosmer-Lemeshow test p value was 0.189 and area under receiver operating
      characteristic curve was 0.826. Applying the German CABG score for 2007 resulted
      in an observed-to-expected mortality ratio of 1.01. CONCLUSION: The German CABG
      score for in-hospital mortality is a risk score with proven validity for isolated
      CABG, developed by means of the patient population in Germany. It can be used for
      the assessment of patient risk groups and for interhospital benchmarking. We
      encourage other researchers to apply and validate this score in comparable health
      care systems.

PMID- 24578038
TI  - Human brain atlas: For high-resolution functional and anatomical mapping.
AB  - We present the new computerized Human Brain Atlas (HBA) for anatomical and
      functional mapping studies of the human brain. The HBA is based on many high
      resolution magnetic resonance images of normal subjects and provides continuous
      updating of the mean shape and position of anatomical structures of the human
      brain. The structures are transformable by linear and nonlinear global and local
      transformations applied anywhere in 3-D pictures to fit the anatomical structures
      of individual brains, which, by reformatting, are transformed into a high
      resolution standard anatomical format. The power of the HBA to reduce anatomical
      variations was evaluated on a randomized selection of anatomical landmarks in
      brains of 27 young normal male volunteers who were different from those on whom
      the standard brain was selected. The HBA, even when based only on standard brain
      surface and central structures, reduced interindividual anatomical variance to
      the level of the variance in structure position between the right and left
      hemisphere in individual brains. (c) 1994 Wiley-Liss, Inc. 

PMID- 24578033
TI  - Exosomes and their role in CNS viral infections.
AB  - Exosomes are small membrane-bound vesicles that carry biological macromolecules
      from the site of production to target sites either in the microenvironment or at
      distant sites away from the origin. Exosomal content of cells varies with the
      cell type that produces them as well as environmental factors that alter the
      normal state of the cell such as viral infection. Human DNA and RNA viruses alter
      the composition of host proteins as well as incorporate their own viral proteins
      and other cargo into the secreted exosomes. While numerous viruses can infect
      various cell types of the CNS and elicit damaging neuropathologies, few have been
      studied for their exosomal composition, content, and function on recipient cells.
      Therefore, there is a pressing need to understand how DNA and RNA viral
      infections in CNS control exosomal release. Some of the more recent studies
      including HIV-1, HTLV-1, and EBV-infected B cells indicate that exosomes from
      these infections contain viral miRNAs, viral transactivators, and a host of
      cytokines that can control the course of infection. Finally, because exosomes can
      serve as vehicles for the cellular delivery of proteins and RNA and given that
      the blood-brain barrier is a formidable challenge in delivering therapeutics to
      the brain, exosomes may be able to serve as ideal vehicles to deliver protein or
      RNA-based therapeutics to the brain. 

PMID- 24578037
TI  - Anterior muscle and neurovascular-sparing thoracotomy and posterolateral
      thoracotomy: postoperative pain and morbidity assessment.
AB  - BACKGROUND: We conducted this study to evaluate the thoracotomy approaches
      commonly used nowadays for treating thoracic pathologies and to decide whether it
      was necessary to make a choice between them for different situations. We used
      prospective analysis to compare hospital stay, analgesic usage, morbidity and
      postoperative chest pain between anterior muscle and neurovascular-sparing
      thoracotomy (AST) with disconnection of anterior rib cartilage, and serratus
      sparing posterolateral thoracotomy (PLT). We also looked for a correlation
      between localization of the lesion and thoracotomy type for this factors.
      MATERIALS AND METHODS: A total of 152 patients who had undergone a thoracotomy
      for major lung surgery from January through November 2011 were recruited in this
      study. Of these, 52 patients received AST and 100 underwent PLT. Location of the
      lesions in the thoracic cavity and all detected postoperative complications were
      documented. Postoperative chest pain was evaluated using a PIQ-6 pain
      questionnaire. Analgesic usage and duration of hospitalization were also noted.
      RESULTS: Pain questionnaire scores were equivalent for both groups in all of the
      evaluations. Postoperative total median narcotic analgesic usage was lower in AST
      group than in PLT group. Complication rates were close in both groups. Median
      hospital stay was also shorter in patients who received AST. CONCLUSION: We
      conclude that AST is a reasonable thoracotomy alternative to standard PLT for
      major lung surgery. But our study fails to demonstrate a clear advantage
      regarding postoperative pain and complications.

PMID- 24578039
TI  - Micromapping of the human brain: Three-dimensional imaging of immunofluorescence
      and dendritic morphology using dual-channel confocal laser scanning microscopy.
AB  - A strategy for investigating neuronal networks at the microscopic level is
      described. The Lucifer Yellow microinjection technique was combined with
      immunofluorescence on human brain material, which was then studied in a confocal
      laser scanning microscope with dual-channel scanning and equipped with an
      argon/krypton laser. The three-dimensional architecture of the Lucifer Yellow
      injected neurons was investigated after transfer of the scanned frames in file
      format to a Silicon Graphics IRIS computer, using VoxelView software from Vital
      Images Inc. Microinjection of Lucifer Yellow revealed the dendritic morphology of
      various types of cells in different brain areas. Indirect immunofluorescence,
      with Texas Red as the secondary label, was used to determine the distribution of
      various categories of macromolecules (enzymes, receptor protein, and synaptic
      vesicle proteins) in the brain slices. We used single- as well as dual-channel
      confocal laser scanning microscopy for imaging these double-stained fluorescent
      specimens. Using these techniques in combination, we have created and saved three
      dimensional confocal images of detailed morphology (axons and dendrites with
      spines and varicosities) of individual cells, together with the localization of
      immunofluorescence. These three-dimensional confocal images will be collected in
      a database for probable future use in human brain mapping. (c) 1994 Wiley-Liss,
      Inc. 

PMID- 24578040
TI  - Regional brain activity when selecting a response despite interference: An H2
      (15) O PET study of the stroop and an emotional stroop.
AB  - The Stroop interference test requires a person to respond to specific elements of
      a stimulus while suppressing a competing response. Previous positron emission
      tomography (PET) work has shown increased activity in the right anterior
      cingulate gyrus during the Stroop test. It is unclear, however, whether the
      anterior cingulate participates more in the attentional rather than the response
      selection aspects of the task or whether different interference stimuli might
      activate different brain regions. We sought to determine (1) whether the Stroop
      interference task causes increased activation in the right anterior cingulate as
      previously reported, (2) whether this activation varied as a function of response
      time, (3) what brain regions were functionally linked to the cingulate during
      performance of the Stroop, and (4) whether a modified Stroop task involving
      emotionally distracting words would activate the cingulate and other limbic and
      paralimbic regions. Twenty-one healthy volunteers were scanned with H2 (15) O PET
      while they performed the Stroop interference test (standard Stroop), a modified
      Stroop task using distracting words with sad emotional content (sad Stroop), and
      a control task of naming colors. These were presented in a manner designed to
      maximize the response selection aspects of the task. Images were stereotactically
      normalized and analyzed using statistical parametric mapping (SPM). Predictably,
      subjects were significantly slower during the standard Stroop than the sad Stroop
      or the control task. The left mideingulate region robustly activated during the
      standard Stroop compared to the control task. The sad Stroop activated this same
      region, but to a less significant degree. Correlational regional network analysis
      revealed an inverse relationship between activation in the left mideingulate and
      the left insula and temporal lobe. Additionally, activity in different regions of
      the cingulate gyrus correlated with performance speed during the standard Stroop.
      These results suggest that the left midcingulate is likely to be part of a neural
      network activated when one attempts to override a competing verbal response.
      Finally, the left midcingulate region appears to be functionally coupled to the
      left insula, temporal, and frontal cortex during cognitive interference tasks
      involving language. These results underscore the important role of the cingulate
      gyrus in selecting appropriate and suppressing inappropriate verbal responses.
      (c) 1994 Wiley-Liss, Inc. 

PMID- 24578041
TI  - Assessing the significance of focal activations using their spatial extent.
AB  - Current approaches to detecting significantly activated regions of cerebral
      tissue use statistical parametric maps, which are thresholded to render the
      probability of one or more activated regions of one voxel, or larger, suitably
      small (e. g., 0.05). We present an approximate analysis giving the probability
      that one or more activated regions of a specified volume, or larger, could have
      occurred by chance. These results mean that detecting significant activations no
      longer depends on a fixed (and high) threshold, but can be effected at any
      (lower) threshold, in terms of the spatial extent of the activated region. The
      substantial improvement in sensitivity that ensues is illustrated using a power
      analysis and a simulated phantom activation study. (c) 1994 Wiley-Liss, Inc. 

PMID- 24578042
TI  - Functional imaging of procedural motor learning: Relating cerebral blood flow
      with individual subject performance.
AB  - Changes of local synaptic activity during acquisition of a visuomotor skill were
      examined with positron emission tomography (PET) imaging of regional cerebral
      blood flow (rCBF). Eight subject learned the pursuit rotor task, a predictable
      tracking task, during three sequential PET scans (day 1). Subjects returned 2
      days later and repeated the three pursuit trials and PET scans (day 2) after
      completing an extensive practice session. Control scans without movement
      bracketed the pursuit trials on both days to rule out time effects unrelated to
      motor skill learning. PET images were transformed to a common stereotaxic space
      using matched magnetic resonance imaging (MRI) scans. Group learning effects were
      determined by a repeated measures multivariate analysis of variance (ANOVA).
      During motor skill acquisition (day 1), increases of synaptic activity were
      identified in cortical motor areas and cerebellum, supporting the hypothesis that
      procedural motor learning occurs in motor execution areas. During long-term
      practice (day 2), changes were limited to the bilateral putamen, bilateral
      parietal cortex, and left premotor cortex. To characterize differences in the
      rate of learning between subjects, each subject's performance data from day 1 was
      fit with a power function. The exponents were correlated with rCBF data on a
      pixel-by-pixel basis. Rapid skill acquisition was associated with increasing rCBF
      in premotor, prefrontal, and cingulate areas, and decreasing rCBF in visual
      processing areas located in the temporal and occipital cortex. This pattern in
      fast learners may reflect a more rapid shift from a visually guided strategy
      (accessing perceptual areas) to an internally generated model (accessing premotor
      and prefrontal areas). (c) 1994 Wiley-Liss, Inc. 

PMID- 24578043
TI  - Obitury.

PMID- 24578046
TI  - Demographic parameters of Phyllocoptes adalius (Acari: Eriophyoidea) and
      influence of insemination on female fecundity and longevity.
AB  - The biology of Phyllocoptes adalius Keifer (Acari: Eriophyoidea) and influence of
      insemination on female fecundity and longevity were studied. The experiment was
      conducted at a constant temperature of 25 +/- 0.5  degrees C, 70-80 % RH and 16-h
      photoperiod. A modified method of mite rearing on detached leaves in closed cells
      was successfully applied and demonstrated to be efficient for biological studies
      of eriophyoids. Survival and development duration of the immature stages, as well
      as fecundity of female and longevity of adults, were calculated. The longest time
      of development was observed for eggs, which was almost twice as long as that for
      larvae and nymphs. Egg-to-adult development did not significantly differ between
      males and females. Survival rate for the immature stages was highest for nymphs
      (98.2 %), exceeding 86.2 % for overall pre-adult stages. Life table parameters of
      P. adalius were estimated as follows: mean generation time (T), 15.8 days;
      doubling time (Dt), 3.3 days; net reproductive rate (R0), 27.8 female
      eggs/female; the intrinsic rate of natural increase (r m ), 0.21 female
      eggs/female/day; the finite rate of increase (lambda), 1.23 female
      eggs/female/day; and sex ratio (proportion females), 0.82. Our studies indicate
      that P. adalius has the potential for rapid population increase, becoming one of
      the most important rose mite species.

PMID- 24578047
TI  - Soil transfers from valley oak (Quercus lobata Nee) stands increase
      ectomycorrhizal diversity and alter root and shoot growth on valley oak
      seedlings.
AB  - Soils from valley oak (Quercus lobata Nee) riparian areas of the Cosumnes River
      Nature Conservancy Preserve near Sacramento, California were added to growth
      medium of valley oak seedlings grown in a greenhouse or in agricultural fields at
      Cosumnes which probably once supported valley oak trees and are now replanted
      with native riparian vegetation or allowed to revegetate naturally. Agricultural
      field soil from the Cosumnes River Preserve was presumed to be low or lacking in
      ectomycorrhizal inoculum. The study was designed to (1) determine whether valley
      oak stand soil transfer could cause mycorrhizal infection on valley oak seedlings
      in an agricultural field and in a greenhouse, (2) describe ectomycorrhizal
      morphological types formed on valley oak seedlings, and (3) determine whether
      seedling growth is enhanced more by transfer of natural valley oak stand soil
      than agricultural field soil. In the field study, transfer of forest soil
      increased average ectomycorrhizal diversity (2.4 types) more than transfer of
      agricultural field soil (1.2 types). Valley oak seedlings were responsive to
      ectomycorrhizal infection in the field study. With increase in mycorrhizal
      infection there was an increase in shoot growth at the expense of root growth. In
      the greenhouse study, both percent mycorrhizal infection and mycorrhizal
      diversity were increased more by transfer of oak forest and woodland soils than
      agricultural field soil. Eight morphotypes occurred on seedlings in forest and
      woodland soils but only three morphotypes in agricultural soil. This result
      strongly suggests that the agricultural field also harbors ectomycorrhizal
      propagules but forest and woodland soils support a more abundant and diverse
      ectomycorrhizal flora. 

PMID- 24578044
TI  - Complement-dependent cytotoxicity (CDC) to detect Anti-HLA antibodies: old but
      gold.
AB  - BACKGROUND: The criterion (gold) standard to detect anti-human leukocyte antigen
      (HLA) antibodies is the complement-dependent cytotoxicity (CDC) assay. Recently,
      more sensitive methods have been used for the same purpose. METHODS: This study
      analyzed 70 serum samples of patients with end-stage renal disease using CDC, CDC
      with the addition of anti-human globulin (CDC-AHG), CDC with the addition of
      dithiothreitol (CDC-DTT), and the recent solid-phase immunoassay (SPI; Labscreen
      PRA) to detect anti-HLA antibodies. RESULTS: Mean percent panel reactive
      antibodies (PRA) detected by SPI was 37.5% (+/-34.2) higher than the values
      detected by the other methods. Comparative analyses revealed significant
      difference between CDC and CDC-AHG, and between CDC and SPI (P < 0.0001), but not
      between CDC-AHG and SPI (P = 0.8026). CONCLUSION: Although the CDC-AHG method is
      "old," its performance to detect anti-HLA antibodies in the samples analyzed was
      comparable to the SPI in the evaluation of percent class I PRA.

PMID- 24578048
TI  - Tissue magnesium and calcium affect arbuscular mycorrhiza development and fungal
      reproduction.
AB  - Applications of high levels of MgSO4 resulted in reduced root colonization and
      sporulation by Glomus sp. (INVAM isolate FL329) with sweet potato and onion in
      aeroponic and sand culture, respectively. Onion shoot-Mg concentrations were
      elevated when a nutrient solution containing 2.6 or 11.7 mM MgSO4 was applied.
      Magnesium application depressed tissue-Ca levels. With lower Ca in the tissue,
      colonization was reduced from > 30% of root length to < 10%, and sporulation from
      > 1200 to ca. 200 spores per plant, 10 weeks after transplantation and the start
      of nutrient application. These effects on colonization and sporulation were
      independent of changes in tissue-P concentration. High Mg/low Ca tissue
      concentrations induced premature root senescence, which may have disrupted the
      mycorrhizal association. Our results confirm the importance of Ca for the
      maintenance of a functioning mycorrhiza. 

PMID- 24578049
TI  - Genetic diversity of the ectomycorrhizal fungus Pisolithus tinctorius based on
      RAPD-PCR analysis.
AB  - Twenty Pisolithus tinctorius isolates from different geographic locations and
      different hosts were characterized by the random amplified polymorphic DNA
      technique. Thirteen arbitrary primers generated 87 DNA fragments, all of them
      polymorphic. These data were used to calculate genetic distances among the
      isolates. The pairwise genetic distances ranged from 1 to 100%, with an average
      of 58.7%. Cluster analysis based on the amplified fragments grouped the isolates
      according to their host and geographical origins. Group I contained isolates
      collected in Brazil and group II those collected in the Northern Hemisphere. In
      addition to the diversity seen at the molecular level, the isolates also showed
      host specificity. Greenhouse experiments demonstrated that isolates from the
      Northern Hemisphere colonized mainly Pinus whereas isolates from Brazil colonized
      only Eucalyptus. The molecular data suggest that the Pisolithus tinctorius
      isolates analyzed belong to two distinct groups. The data also suggest new
      guidelines for future investigations on the taxonomy and systematic of this
      important fungus species. Furthermore, these results support future experiments
      aimed at the selection and development of improved isolates of P. tinctorius. 

PMID- 24578050
TI  - Effects of inoculation of phosphate-solubilizing microorganisms and an arbuscular
      mycorrhizal fungus on mungbean grown under natural soil conditions.
AB  - The effect of inoculation of the phosphate-solubilizing microorganisms (PSM)
      Bacillus circulans and Cladosporium herbarum and the arbuscular mycorrhizal (AM)
      fungus Glomus fasciculatum with or without Mussoorie rockphosphate (MRP) was
      studied in a P-deficient natural non-disinfected sandy soil on mungbean (Vigna
      radiata). The AM levels increased following the addition of MRP or inoculation
      with PSM or G. fasciculatum. Both grain and straw yield of mungbean increased
      following inoculation with PSM or the AM fungus. In general, the increase in
      yield was higher in the presence of MRP and inoculation with a combination of PSM
      and AM fungus. Highest N and P uptake by mungbean was recorded after treatment
      with a combination of B. circulans, C. herbarum and G. fasciculatum in the
      presence of MRP. Generally the PSM population increased after AM fungus
      inoculation. 

PMID- 24578051
TI  - Assimilation of inorganic nitrogen by a mycobiont isolated from Pisonia grandis
      R. Br. (Nyctaginaceae) mycorrhiza.
AB  - Single isolates of a mycobiont isolated from Pisonia grandis R. Br., Pisolithus
      tinctorius (Pers.) Coker & Couch and Tylospora fibrillosa (Burt.) Donk were
      compared with regard to their relative abilities to produce key enzymes of
      inorganic nitrogen assimilation. Nitrate reductase (NR) activities in the P.
      grandis mycobiont and T. fibrillosa were significantly lower than in P.
      tinctorius. While specific activities for glutamate dehydrogenase (GDH) were
      higher in P. tinctorius than the other two fungi following NH4 (+) pre-treatment,
      glutamine synthetase (GS) activity did not differ significantly between the three
      fungi. In all three fungi, specific activities for GS were significantly higher
      than for GDH. NR activity was expressed in all three fungi regardless of the
      nitrogen source in the medium, but in P. tinctorius diminished following
      continued exposure to either NO3 (-), NH4 (+), glutamine or NO3 (-) + glutamine.
      The data are discussed in relation to nitrogen utilisation by the P. grandis
      mycobiont. 

PMID- 24578052
TI  - Mycorrhizal functioning of Phialocephala fortinii with Pinus contorta on glacier
      forefront soil: interactions with soil nitrogen and organic matter.
AB  - Plants growing on an environmentally stressed glacier forefront on soil low in N
      and organic matter have abundant root colonizations by dark-septate fungi. As the
      plants appeared fit for this severe habitat, it was hypothesized that the dark
      septate endophytes were neutral or beneficial rather than detrimental to the
      plants. To test this hypothesis, we designed a growth-room experiment with Pinus
      contorta grown on forefront soil inoculated with the dark-septate fungus
      Phialocephala fortinii in the absence of climatic stress. N and organic matter
      treatments were included to explore their interaction with the fungal
      inoculation. P. fortinii colonized roots inter- and intracellularly and
      occasionally formed microsclerotia. Inoculated plants absorbed significantly more
      P than noninoculated plants in all combinations of N and organic matter. Without
      added N, neither inoculation nor organic matter addition improved plant growth or
      N uptake, showing that N indeed limits plant growth in this substrate. With added
      N, however, both organic matter addition and inoculation significantly increased
      total pine biomass and N uptake. The enhanced P uptake by the P. fortinii
      inoculated pine as well as the increased pine growth and N uptake in the
      treatment combining P. fortinii and N appear as typical mycorrhizal responses. 

PMID- 24578053
TI  - Xerocomus badius - Picea abies, an ectomycorrhiza of high activity and element
      storage capacity in acidic soil.
AB  - Mycorrhizas were collected from three Norway spruce (Picea abies) stands in
      southwest Germany, sorted on the morphotype level and analysed by fluorescein
      diacetate vital fluorescence staining and the accumulation of elements using
      inductively coupled plasma-atomic emission spectrometry (ICP-AES) and electron
      energy-loss spectroscopy (EELS). Xerocomus badius - Picea abies mycorrhizas
      showed a higher frequency of active hyphal sheaths and a higher potential to
      store nitrogen, phosphorus, potassium, magnesium, iron and zinc than other
      mycorrhizal types. Phosphorus and nitrogen were localized by EELS in vacuolar
      bodies which occurred consistently in the sheath of X. badius mycorrhizas. The
      results indicate that X. badius is well adapted to acidic stands and that its
      mycorrhizas are very efficient in uptake and storage of macronutrients. 

PMID- 24578054
TI  - Influence of OSEM and segmented attenuation correction in the calculation of
      standardised uptake values for [(18)F]FDG PET.
AB  - Standardised Uptake Values (SUVs) are widely used in positron emission tomography
      (PET) as a semi-quantitative index of fluorine-18 labelled fluorodeoxyglucose
      uptake. The objective of this study was to investigate any bias introduced in the
      calculation of SUVs as a result of employing ordered subsets-expectation
      maximisation (OSEM) image reconstruction and segmented attenuation correction
      (SAC). Variable emission and transmission time durations were investigated. Both
      a phantom and a clinical evaluation of the bias were carried out. The software
      implemented in the GE Advance PET scanner was used. Phantom studies simulating
      tumour imaging conditions were performed. Since a variable count rate may
      influence the results obtained using OSEM, similar acquisitions were performed at
      total count rates of 34 kcps and 12 kcps. Clinical data consisted of 100 patient
      studies. Emission datasets of 5 and 15 min duration were combined with 15-, 3-, 2
      and 1-min transmission datasets for the reconstruction of both phantom and
      patient studies. Two SUVs were estimated using the average (SUVavg) and the
      maximum (SUVmax) count density from regions of interest placed well inside
      structures of interest. The percentage bias of these SUVs compared with the
      values obtained using a reference image was calculated. The reference image was
      considered to be the one produced by filtered backprojection (FBP) image
      reconstruction with measured attenuation correction using the 15-min emission and
      transmission datasets for each phantom and patient study. A bias of 5%-20% was
      found for the SUVavg and SUVmax in the case of FBP with SAC using variable
      transmission times. In the case of OSEM with SAC, the bias increased to 10%-30%.
      An overall increase of 5%-10% was observed with the use of SUVmax. The 5-min
      emission dataset led to an increase in the bias of 25%-100%, with the larger
      increase recorded for the SUVmax. The results suggest that OSEM and SAC with 3
      and 2 min transmission may be reliably used to reduce the overall data
      acquisition time without compromising the accuracy of SUVs. 

PMID- 24578055
TI  - Clinical role of (99m)TcO 4/MIBI scan, ultrasound and intra-operative gamma probe
      in the performance of unilateral and minimally invasive surgery in primary
      hyperparathyroidism.
AB  - The main purposes of this study were: (a) to investigate the efficacy of an
      imaging protocol based on the combination of (99m)TcO4/MIBI scintigraphy and neck
      ultrasound (US) in selecting patients with primary hyperparathyroidism (HPT) for
      unilateral neck exploration, and (b) to help define the role of the
      intraoperative MIBI gamma probe (IMGP) technique in the performance of minimally
      invasive radio-guided surgery (MIRS). One hundred and forty-three consecutive
      patients with primary HPT were enrolled in the study. We used a modified
      (99m)TcO4/MIBI scintigraphic procedure which included the oral administration of
      potassium perchlorate to cause rapid (99m)TcO4 washout from the thyroid tissue,
      thereby permitting the acquisition of high-quality early MIBI images. A single
      photon emission tomography (SPET) acquisition was also obtained in 21 patients,
      of whom seven had an enlarged parathyroid gland (EPG) in the mediastinum at
      planar scintigraphy and 14 had discordant scan/US findings for the presence of a
      cervical EPG. Neck US was performed in the same session as scintigraphy using a
      small-parts, high-resolution 10-MHz transducer. All patients were then operated
      on by the same surgical team. Quick PTH assay (QPTH) was used to measure PTH
      intraoperatively to confirm successful parathyroidectomy. In patients with
      scan/US evidence of a solitary EPG and with a normal thyroid gland, limited,
      unilateral neck surgery or, more recently, MIRS was planned (n=91). In patients
      with scan/US evidence of multiglandular disease (MGD) (n=21) or concomitant
      nodular goitre (n=24) or in patients with a negative scan/US evaluation (n=7),
      extensive bilateral neck exploration was planned (n=52). In 87 of the 91 patients
      (95.6%) in whom preoperative imaging indicated the presence of a solitary EPG and
      a normal thyroid gland, a single parathyroid adenoma was found at surgery, and
      these patients were treated by unilateral neck exploration or MIRS. In the
      remaining four patients of this group, conversion to bilateral neck exploration
      was required because parathyroid carcinoma (n=3) or MGD (n=1) was diagnosed at
      operation. In some cases SPET was helpful in better localising the EPG. In
      particular, in 5 of the 21 patients evaluated, SPET localised an EPG deep in the
      neck or mediastinum and at surgery a parathyroid adenoma was found in the
      paratracheal or para-oesophageal space. In 43 of the 46 patients (93.5%) who were
      candidates for MIRS, the IMGP technique allowed parathyroidectomy to be performed
      through a small, 2- to 2.5-cm skin incision with a short duration of intervention
      (mean 34 min). We conclude that: (a) The integrated scan/US imaging protocol that
      we used appears to be accurate in selecting patients with primary HPT for
      unilateral neck exploration. (b) In our series the most prevalent cause of
      bilateral neck exploration was the co-existence of a nodular goitre; thus
      accurate preoperative evaluation of the thyroid gland by dual-tracer scintigraphy
      and US imaging is strongly recommended in all patients with HPT. (c) SPET can
      provide the surgeon with useful information when an EPG is located deep in the
      neck or mediastinum. (d) IMGP appears to be a useful intraoperative device in HPT
      patients with solitary parathyroid adenomas and a normal thyroid gland, since it
      permits minimally invasive and time-saving surgery. 

PMID- 24578056
TI  - Biodistribution and dosimetry of (99m)Tc-BTAP-annexin-V in humans.
AB  - The purpose of this study was to determine the biodistribution and the associated
      radiation dose of technetium-99m 4,5-bis(thioacetamido)pentanoyl-annexin-V
      ((99m)Tc-Apomate), a tracer proposed for the study of apoptosis. Eight patients
      (including two females) with normal kidney and liver functions were included in
      the study. An activity of 580+/-90 MBq of (99m)Tc-Apomate was injected
      intravenously, immediately followed by a dynamic study of 30 frames of 1 min
      each. At about 1 h, 4 h and 20 h p.i., whole-body scans were acquired. All
      activity distributions were measured using a dual-head gamma camera. Before
      injection of activity, a transmission scan with a cobalt-57 flood source had been
      performed to determine patient attenuation. Blood samples were taken every 10 min
      during the first hour after injection, and at about 4 and 20 h. Urine and faeces
      were collected during the first 20 h. Organ uptake was estimated after correction
      for body background activity, attenuation and scatter. Residence times were
      calculated from the dynamic and whole-body studies and used as input in the
      Mirdose 3.1 program to obtain organ doses and effective dose. It was found that
      radioactivity strongly accumulated in the kidneys and the liver [at 70 min p.i.,
      28%+/-8% and 20%+/-4% of the injected dose (ID), respectively]. Uptake in the
      target tissues (lymphomas or heart) was negligible from a dosimetric point of
      view. Extrapolating data from the first 20 h, one finds that approximately 73% of
      the ID will be excreted in the urine, and 27% in the faeces. The biological half
      life of the activity in the total body was 16+/-7 h. Some organ doses +/-
      standard deviation (SD) in uGy/MBq were: kidneys 63+/-22, urinary bladder 20+/-6,
      spleen 15+/-3, liver 13+/-3, upper large intestine 12+/-6, lower large intestine
      8+/-4, testes 6+/-2 and red bone marrow 4+/-0.7. The effective dose was 7.6+/-0.5
      uSv/MBq, corresponding to a total effective dose of 4.6+/-0.3 mSv for a nominal
      injected activity of 600 MBq. In conclusion, (99m)Tc-Apomate has a high uptake in
      the kidneys and liver - in fact a factor of 1.3-1.6 higher than that found for
      the previously studied (99m)Tc-(n-1-imino-4-mercaptobutyl)-annexin-V. The
      biological half-life is shorter, however, but still long compared with the
      physical half-life of (99m)Tc. The faster appearance of activity in the
      intestines may preclude imaging of apoptosis in the abdomen. The effective dose
      is within the lower range of values reported for typical (99m)Tc compounds. 

PMID- 24578057
TI  - Reply.

PMID- 24578058
TI  - Bone marrow uptake of (99m)Tc-MIBI in patients with multiple myeloma.

PMID- 24578059
TI  - Erratum to: Somatostatin receptor sst1-sst5 expression in normal and neoplastic
      human tissues using receptor autoradiography with subtype-selective ligands.

PMID- 24578060
TI  - The prognostic value of myocardial perfusion scintigraphy: investigators, are you
      (mis)leading us?

PMID- 24578062
TI  - Is it time to write a review article?

PMID- 24578061
TI  - Core curriculum illustration: testicular torsion.
AB  - This is the 7th installment of a series that will highlight one case per
      publication issue from the bank of cases available online as part of the American
      Society of Emergency Radiology (ASER) educational resources. Our goal is to
      generate more interest in and use of our online materials. To view more cases
      online, please visit the ASER Core Curriculum and Recommendations for Study
      online at http://www.aseronline.org/curriculum/toc.htm .

PMID- 24578066
TI  - Quantification of facial skeletal shape variation in fibroblast growth factor
      receptor-related craniosynostosis syndromes.
AB  - BACKGROUND: fibroblast growth factor receptor (FGFR) -related craniosynostosis
      syndromes are caused by many different mutations within FGFR-1, 2, 3, and certain
      FGFR mutations are associated with more than one clinical syndrome. These
      syndromes share coronal craniosynostosis and characteristic facial skeletal
      features, although Apert syndrome (AS) is characterized by a more dysmorphic
      facial skeleton relative to Crouzon (CS), Muenke (MS), or Pfeiffer syndromes.
      METHODS: Here we perform a detailed three-dimensional evaluation of facial
      skeletal shape in a retrospective sample of cases clinically and/or genetically
      diagnosed as AS, CS, MS, and Pfeiffer syndrome to quantify variation in facial
      dysmorphology, precisely identify specific facial features pertaining to these
      four syndromes, and further elucidate what knowledge of the causative FGFR
      mutation brings to our understanding of these syndromes. RESULTS: Our results
      confirm a strong correspondence between genotype and facial phenotype for AS and
      MS with severity of facial dysmorphology diminishing from Apert FGFR2(S252W) to
      Apert FGFR2(P253R) to MS. We show that AS facial shape variation is increased
      relative to CS, although CS has been shown to be caused by numerous distinct
      mutations within FGFRs and reduced dosage in ERF. CONCLUSION: Our quantitative
      analysis of facial phenotypes demonstrate subtle variation within and among
      craniosynostosis syndromes that might, with further research, provide information
      about the impact of the mutation on facial skeletal and nonskeletal development.
      We suggest that precise studies of the phenotypic consequences of genetic
      mutations at many levels of analysis should accompany next-generation genetic
      research and that these approaches should proceed cooperatively.

PMID- 24578068
TI  - Coaxial carbon/metal oxide/aligned carbon nanotube arrays as high-performance
      anodes for lithium ion batteries.
AB  - Coaxial carbon/metal oxide/aligned carbon nanotube (ACNT) arrays over stainless
      steel foil are reported as high-performance binder-free anodes for lithium ion
      batteries. The coaxial arrays were prepared by growth of ACNTs over stainless
      steel foil followed by coating with metal oxide and carbon. The carbon/manganese
      oxide/ACNT arrays can deliver an initial capacity of 738 mAh g(-1) with 99.9 %
      capacity retention up to 100 cycles and a capacity of 374 mAh g(-1) at a high
      current density of 6000 mA g(-1). The external carbon layer was recognized as a
      key component for high performance, and the mechanism of performance enhancement
      was investigated by electrochemical impedance spectroscopy, electron microscopy,
      and X-ray diffraction analysis. The layer increases rate capability by enhancing
      electrical conductivity and maintaining a low mass-transfer resistance and also
      improves cyclic stability by avoiding aggregation of metal-oxide particles and
      stabilizing the solid electrolyte interface. The resultant principle of rational
      electrode design was applied to an iron oxide-based system, and similar
      improvements were found. These coaxial nanotube arrays present a promising
      strategy for the rational design of high-performance binder-free anodes for
      lithium ion batteries.

PMID- 24578067
TI  - A unique DNA methylation signature defines a population of IFN-gamma/IL-4 double
      positive T cells during helminth infection.
AB  - Th1 and Th2 cell fates are traditionally viewed as mutually exclusive, but recent
      work suggests that these lineages may be more plastic than previously thought.
      When isolating splenic CD4(+) T cells from mice infected with the parasitic
      helminth Schistosoma mansoni, we observed a defined population of IFN-gamma/IL-4
      double-positive cells. These IFN-gamma(+) IL-4(+) cells showed differences in DNA
      methylation at the Ifng and Il4 loci when compared with IFN-gamma(+) IL-4(-)
      (Th1) and IFN-gamma(-) IL-4(+) (Th2) cells, demonstrating that they represent a
      distinct effector cell population. IFN-gamma(+) IL-4(+) cells also displayed a
      discrete DNA methylation pattern at a CpG island within the body of the Gata3
      gene, which encodes the master regulator of Th2 identity. DNA methylation at this
      region correlated with decreased Gata3 levels, suggesting a possible role in
      controlling Gata3 expression. These data provide important insight into the
      molecular mechanisms behind the co-existence of Th1 and Th2 characteristics. 

PMID- 24578069
TI  - Science at the supermarket: multiplication, personalization and consumption of
      science in everyday life.
AB  - Which is the kind science's psychological guidance upon everyday life? I will try
      to discuss some issues about the role that techno-scientific knowledge plays in
      sense-making and decision making about practical questions of life. This relation
      of both love and hate, antagonism and connivance is inscribable in a wider debate
      between a trend of science to intervene in fields that are traditionally
      prerogative of political, religious or ethical choices, and, on the other side,
      the position of those who aim at stemming "technocracy" and governing these
      processes. I argue that multiplication, personalization and consumption are the
      characteristics of the relationship between science, technology and society in
      the age of "multiculturalism" and "multi-scientism". This makes more difficult
      but intriguing the study and understanding of the processes through which
      scientific knowledge is socialized. Science topics, like biotech, climate change,
      etc. are today an unavoidable reference frame. It is not possible to not know
      them and to attach them to the most disparate questions. Like in the case of
      Moscovici's "Freud for all seasons", the fact itself that the members of a group
      or a society believe in science as a reference point for others, roots its social
      representation and the belief that it can solve everyday life problems. 

PMID- 24578070
TI  - The language of cancer.

PMID- 24578071
TI  - Comment on "healthcare professionals' response to cachexia in advanced cancer: a
      qualitative study".

PMID- 24578072
TI  - Rationale for promoting physical activity among cancer survivors: literature
      review and epidemiologic examination.
AB  - PURPOSE/OBJECTIVES: To review the extant literature on the link between physical
      activity and health outcomes among cancer survivors; identify evidence-based
      strategies to promote physical activity among this population; and conduct an
      epidemiologic study based on gaps from the literature review, examining the
      association between physical activity and various biologic markers. DATA SOURCES:
      The authors used PubMed and Google Scholar up to July 2013, as well as data from
      the 2003-2006 National Health and Nutrition Examination Survey for the empirical
      study. DATA SYNTHESIS: Studies were examined through a systematic review process.
      In the epidemiologic study, 227 adult cancer survivors wore an accelerometer for
      four days or longer, with biologic markers (e.g., cholesterol) assessed from a
      blood sample. CONCLUSIONS: The review study demonstrated that cancer survivors
      are relatively inactive, but physical activity may help to reduce the risk of
      cancer recurrence and cancer-related mortality, increase cancer treatment rates,
      reduce pain and other side effects associated with cancer treatment, and improve
      physical and mental health. The epidemiologic study showed that physical activity
      was associated with several understudied biomarkers (e.g., neutrophils, white
      blood cells) that are linked with cancer recurrence, cancer-related mortality,
      and other chronic diseases. IMPLICATIONS FOR NURSING: Nurses are encouraged to
      promote physical activity in cancer survivors.

PMID- 24578073
TI  - The nature of ethical conflicts and the meaning of moral community in oncology
      practice.
AB  - PURPOSE/OBJECTIVES: To explore ethical conflicts in oncology practice and the
      nature of healthcare contexts in which ethical conflicts can be averted or
      mitigated. RESEARCH APPROACH: Ethnography. SETTING: Medical centers and community
      hospitals with inpatient and outpatient oncology units in southern California and
      Minnesota. PARTICIPANTS: 30 oncology nurses, 6 ethicists, 4 nurse administrators,
      and 2 oncologists. METHODOLOGIC APPROACH: 30 nurses participated in six focus
      groups that were conducted using a semistructured interview guide. Twelve key
      informants were individually interviewed. Coding, sorting, and constant
      comparison were used to reveal themes. FINDINGS: Most ethical conflicts pertained
      to complex end-of-life situations. Three factors were associated with ethical
      conflicts: delaying or avoiding difficult conversations, feeling torn between
      competing obligations, and the silencing of different moral perspectives. Moral
      communities were characterized by respectful team relationships, timely
      communication, ethics-minded leadership, readily available ethics resources, and
      provider awareness and willingness to use ethics resources. CONCLUSIONS: Moral
      disagreements are expected to occur in complex clinical practice. However, when
      they progress to ethical conflicts, care becomes more complicated and often
      places seriously ill patients at the epicenter. INTERPRETATION: Practice
      environments as moral communities could foster comfortable dialogue about moral
      differences and prevent or mitigate ethical conflicts and the moral distress that
      frequently follows.

PMID- 24578075
TI  - Feasibility study: home telemonitoring for patients with lung cancer in a
      mountainous rural area.
AB  - PURPOSE/OBJECTIVES: To explore the feasibility of rural home telemonitoring for
      patients with lung cancer. DESIGN: Exploratory, descriptive, observational.
      SETTING: Patient homes within a 75-mile radius of the study hospital in West
      Virginia. SAMPLE: 10 patients hospitalized with lung cancer as a primary or
      secondary-related diagnosis. METHODS: Data included referral and demographics,
      chart reviews, and clinical data collected using a HomMed telemonitor. Five
      patients received usual care after discharge; five had telemonitors set up at
      home for 14 days with daily phone calls for nurse coaching; mid- and end-study
      data were collected by phone and in homes through two months. MAIN RESEARCH
      VARIABLES: Enrollment and retention characteristics, physiologic (e.g.,
      temperature, pulse, blood pressure, weight, O2 saturation) and 10 symptom
      datapoints, patient and family telemonitor satisfaction. FINDINGS: Of 45 referred
      patients, only 10 consented; 1 of 5 usual care and 3 of 5 monitored patients
      completed the entire study. Telemonitored data transmission was feasible in rural
      areas with high satisfaction; symptom data and physiologic data were inconsistent
      but characteristic of lung cancer. CONCLUSIONS: Challenges included environment,
      culture, technology, and overall enrollment and retention. Physiologic and
      symptom changes were important data for nurse coaching on risks, symptom
      management, and clinician contact. IMPLICATIONS FOR NURSING: Enrollment and
      retention in cancer research warrants additional study. Daily monitoring is
      feasible and important in risk assessment, but length of time to monitor signs
      and symptoms, which changed rapidly, is unclear. Symptom changes were useful as
      proxy indicators for physiologic changes, so risk outcomes may be assessable by
      phone for patient self-management coaching by nurses.

PMID- 24578074
TI  - Response to a mobile health decision-support system for screening and management
      of tobacco use.
AB  - PURPOSE/OBJECTIVES: To describe the predictors of nurse actions in response to a
      mobile health decision-support system (mHealth DSS) for guideline-based screening
      and management of tobacco use. DESIGN: Observational design focused on an
      experimental arm of a randomized, controlled trial. SETTING: Acute and ambulatory
      care settings in the New York City metropolitan area. SAMPLE: 14,115 patient
      encounters in which 185 RNs enrolled in advanced practice nurse (APN) training
      were prompted by an mHealth DSS to screen for tobacco use and select guideline
      based treatment recommendations. METHODS: Data were entered and stored during
      nurse documentation in the mHealth DSS and subsequently stored in the study
      database where they were retrieved for analysis using descriptive statistics and
      logistic regressions. MAIN RESEARCH VARIABLES: Predictor variables included
      patient gender, patient race or ethnicity, patient payer source, APN specialty,
      and predominant payer source in clinical site. Dependent variables included the
      number of patient encounters in which the nurse screened for tobacco use,
      provided smoking cessation teaching and counseling, or referred patients for
      smoking cessation for patients who indicated a willingness to quit. FINDINGS:
      Screening was more likely to occur in encounters where patients were female,
      African American, and received care from a nurse in the adult nurse practitioner
      specialty or in a clinical site in which the predominant payer source was
      Medicare, Medicaid, or State Children's Health Insurance Program. In encounters
      where the patient payer source was other, nurses were less likely to provide
      tobacco cessation teaching and counseling. CONCLUSIONS: mHealth DSS has the
      potential to affect nurse provision of guideline-based care. However, patient,
      nurse, and setting factors influence nurse actions in response to an mHealth DSS
      for tobacco cessation. IMPLICATIONS FOR NURSING: The combination of a reminder to
      screen and integration of guideline-based recommendations into the mHealth DSS
      may reduce racial or ethnic disparities to screening, as well as clinician
      barriers related to time, training, and familiarity with resources.

PMID- 24578076
TI  - A pilot study of the feasibility and outcomes of yoga for lung cancer survivors.
AB  - PURPOSE/OBJECTIVES: To determine the feasibility of a standardized yoga
      intervention for survivors of non-small cell lung cancer (NSCLC) and, effects on
      sleep, mood, salivary cortisol levels, and quality of life (QOL). DESIGN: This 14
      week, one-group, repeated-measures study included a three-week preintervention
      phase, eight weeks of yoga classes (40 minutes once per week) and home practice,
      and a three-week postintervention phase. Follow-up occurred at three and six
      months poststudy. SETTING: A community-based cancer support center in the
      midwestern United States. SAMPLE: 7 adults who had completed initial treatment
      for stages I-IIIa NSCLC. METHODS: A standardized yoga protocol was developed
      prior to the study by experts in the field. Breathing ease was monitored before,
      during, and after classes to assess feasibility of movement without compromising
      respiratory status while doing yoga. Data analysis included descriptive
      statistics, repeated-measures analysis of variance, and salivary cortisol
      analysis. MAIN RESEARCH VARIABLES: Sleep quality, mood, salivary cortisol, and
      QOL were assessed using the Pittsburgh Sleep Quality Index, Profile of Mood
      States-Brief, a cortisol measurement, and the Medical Outcomes Survey SF-36(r),
      respectively. Breathing ease was assessed using a dyspnea numeric rating scale as
      well as observation of participants. FINDINGS: Participants with varying stages
      of disease and length of survivorship were able to perform yoga without
      respiratory distress. Class attendance exceeded 95%, and all practiced at home.
      Mood, sleep efficiency, and QOL significantly improved; salivary cortisol levels
      decreased over time. CONCLUSIONS: Yoga was feasible for NSCLC survivors without
      further compromising breathing with movement. Potential benefits were identified,
      supporting the need for future clinical trials with larger samples stratified by
      cancer stage, treatment, and length of survivorship. IMPLICATIONS FOR NURSING:
      Nurses and healthcare providers should consider yoga as a mind-body practice to
      manage stress, improve mood and sleep, and potentially enhance QOL for NSCLC
      survivors.

PMID- 24578077
TI  - Transformative learning theory: facilitating mammography screening in rural
      women.
AB  - PURPOSE/OBJECTIVES: To use transformative learning to investigate what
      experiences serve as catalysts for mammography screening, the cognitive and
      affective responses that result from the catalyst, and how screening behavior is
      impacted. RESEARCH APPROACH: A descriptive qualitative study. SETTING:
      Southeastern Wyoming. PARTICIPANTS: 25 low-income, rural women aged 40 years and
      older. METHODOLOGIC APPROACH: Four focus group interviews. FINDINGS: Cancer
      experiences triggered universal responses of fear by screeners and nonscreeners.
      The manner in which that fear response was interpreted was a critical factor in
      the facilitation of, or impedance to, screening. Dichotomous interpretations of
      fear responses provided the context for screening behavior. Immobilizing and
      isolating experiences were associated with nonscreening behavior, whereas
      motivation and self-efficacy were associated with screening behavior.
      CONCLUSIONS: Transformative learning theory is a useful framework from which to
      explain differences in mammography screening behavior. Creating opportunities
      that facilitate dialogue and critical reflection hold the potential to change
      immobilizing and isolating frames of reference in nonscreening women.
      INTERPRETATION: To help women transcend their fear and become self-efficacious,
      nurses can assess how cancer and the screening experience is viewed and, if
      indicated, move beyond standard education and offer opportunities for dialogue
      and critical reflection.

PMID- 24578079
TI  - Analysis and use of different research review approaches in nursing.

PMID- 24578080
TI  - Tribal alchemy: turning lesser into better, together.

PMID- 24578078
TI  - Association between serotonin transport polymorphisms and postdischarge nausea
      and vomiting in women following breast cancer surgery.
AB  - PURPOSE/OBJECTIVES: To examine the association of the serotonin transport gene
      and postdischarge nausea and vomiting (PDNV) in women following breast cancer
      surgery. DESIGN: A cross-sectional study. SETTING: A comprehensive cancer center
      in Pittsburgh, PA. SAMPLE: 80 post-menopausal women treated surgically for early
      stage breast cancer. METHODS: Data were collected using standardized instruments
      after surgery but before the initiation of chemotherapy. Blood or saliva were
      used for DNA extraction and analyzed following standardized protocols. Data were
      analyzed using descriptive statistics and logistic regression. MAIN RESEARCH
      VARIABLES: Serotonin transport gene (SLC6A4), nausea, vomiting, pain, and
      anxiety. FINDINGS: Women who inherited the LA/LA genotypes were at greater risk
      for nausea and vomiting when compared to women who carried any other combination
      of genotypes. Twenty-one percent of women reported nausea and vomiting an average
      of one month following surgery and prior to initiation of adjuvant therapy. Those
      women who experienced PDNV reported significantly higher anxiety and pain scores.
      CONCLUSIONS: Findings of this study suggest that variability in the genotypes of
      the serotonin transport gene may help to explain the variability in PDNV in women
      following breast cancer surgery and why 20%-30% of patients do not respond to
      antiemetic medications. IMPLICATIONS FOR NURSING: Nurses need to be aware that
      women who do not experience postoperative nausea and vomiting following surgery
      for breast cancer continue to be at risk for PDNV long after they have been
      discharged from the hospital, and this frequently is accompanied by pain and
      anxiety.

PMID- 24578081
TI  - Pegfilgrastim-induced pain in patients with lymphoma.

PMID- 24578083
TI  - Importance of meaning-making for patients undergoing hematopoietic stem cell
      transplantation.
AB  - PURPOSE/OBJECTIVES: The purpose of this integrative literature review of
      hematopoietic stem cell transplantation (HSCT) for hematologic malignancies was
      to determine whether meaning-making might be helpful to improve coping and
      psychological adaptation as patients navigate HSCT. DATA SOURCES: CINAHL(r),
      MEDLINE(r), and PsychINFO databases, and ancestry searches. Search terms included
      bone marrow transplant, hematopoietic stem cell transplant, hematologic
      malignancy, quality of life, lived experience, psychosocial, psychological,
      isolation, and social support. DATA SYNTHESIS: Twenty-four research articles
      published from 1989-2012 were included. Five major themes emerged: (a) lived
      experience, (b) coping style, (c) quality of life, (d) psychological morbidity,
      and (e) potential for post-traumatic growth. Meaning-making was a thread that ran
      through each of the key areas of the HSCT experience. CONCLUSIONS: Physical,
      psychosocial, and spiritual issues arise during HSCT that are unique among
      patients diagnosed with cancer. Meaning-making is key to adaptive coping and
      helps to reduce physical, psychosocial, and spiritual challenges, as well as
      assists patients in experiencing positive personal growth. Interventions focused
      on meaning-making should be tested in this population. IMPLICATIONS FOR NURSING:
      Nurses are positioned to develop and deliver meaning-making interventions for
      patients undergoing HSCT and to assess patient-oriented outcomes.

PMID- 24578084
TI  - Oncology nurses' knowledge of survivorship care planning: the need for education.
AB  - PURPOSE/OBJECTIVES: To survey nurses about their knowledge of cancer survivorship
      care. DESIGN: Descriptive, cross-sectional. SETTING: Midwestern comprehensive
      cancer center. SAMPLE: 223 registered and advanced practice nurses. METHODS:
      Online survey of survivorship knowledge using a 50-item questionnaire derived
      from the Institute of Medicine report and related publications. MAIN RESEARCH
      VARIABLES: Concepts of survivorship care and common long-term symptoms. FINDINGS:
      Most nurses reported having knowledge about healthy lifestyle habits; more than
      50% of nurses reported having knowledge about chemotherapy, surgery, and
      radiation therapy, as well as side effects of fatigue, depression, limitations of
      daily activities, and weight gain; less than 50% of nurses reported having
      knowledge of impact on family, biologic agents, lymphedema, immunizations or
      vaccinations, and osteoporosis screening; less than 40% of nurses reported having
      knowledge about marital and partner relationships, osteoporosis prevention and
      care, sexuality, side effects of bone marrow transplantation, employment issues,
      and angiogenesis agents; and less than 25% of nurses reported having knowledge on
      genetic risks, as well as fertility, financial, and insurance issues.
      CONCLUSIONS: Oncology nurses at an academic comprehensive cancer center reported
      gaps in knowledge consistent with previous studies about knowledge of
      survivorship care. IMPLICATIONS FOR NURSING: The Institute of Medicine has
      challenged oncology providers to address cancer survivorship care planning. Gaps
      in cancer survivorship knowledge are evident and will require focused education
      for this initiative to be successful.

PMID- 24578085
TI  - Quality of life and related factors in patients with newly diagnosed advanced
      lung cancer: a longitudinal study.
AB  - PURPOSE/OBJECTIVES: To examine the changes in quality of life (QOL), symptoms,
      self-efficacy for coping with cancer, and factors related to those changes in
      patients with newly diagnosed advanced lung cancer. DESIGN: Longitudinal and
      correlational. SETTING: Oncology inpatient wards and outpatient departments of a
      medical center in northern Taiwan. SAMPLE: 101 patients newly diagnosed with
      stage IIIB or IV lung cancer. METHODS: Questionnaires were used to assess
      patients' QOL, symptoms, and self-efficacy before treatment and at one and three
      months following treatment. Factors related to the changes in global QOL and five
      functional dimensions were analyzed using six generalized estimating equation
      models. MAIN RESEARCH VARIABLES: QOL, symptoms, and self-efficacy for coping with
      cancer. FINDINGS: Patients reported moderate levels of global QOL, symptom
      severity, and self-efficacy for coping with cancer. They also reported high
      physical and cognitive functions, but relatively low role and social functions.
      Factors were significantly related to the most functional dimensions, including
      self-efficacy, fatigue, pain, sleep difficulties, and demographic- and disease
      related factors. Self-efficacy was the most robust factor for predicting QOL.
      CONCLUSIONS: Patients with advanced lung cancer experience a compromised global
      QOL and relatively low social and role functioning during the first three months
      following cancer diagnosis. Levels of self-efficacy and symptoms significantly
      affected changes in QOL and functioning. IMPLICATIONS FOR NURSING: Applying a
      systematic assessment of changes in QOL and developing comprehensive
      interventions with self-efficacy training and symptom management are strongly
      recommended for clinical care to improve the QOL of patients with advanced lung
      cancer.

PMID- 24578086
TI  - Oncology rehabilitation outcomes over time: a mixed-methods approach.
AB  - PURPOSE/OBJECTIVES: To evaluate an oncology rehabilitation program over time.
      DESIGN: A cross-sectional, retrospective program evaluation using a mixed-methods
      approach. SETTING: An outpatient oncology rehabilitation program housed in an
      urban, hospital-based comprehensive cancer center in Alaska. SAMPLE: 102 cancer
      survivors who had completed a 10-week oncology rehabilitation program (mean time
      since completion was 2.5 years). METHODS: Participants completed a mailed, 28
      item retrospective survey to collect perceived activity level recalled at various
      points in time as well as program perceptions. Open-ended questions elicited
      narrative comments about motivators and barriers. The Medical Outcomes Study
      (MOS) SF-36(r) was completed before and after the program. MAIN RESEARCH
      VARIABLES: Health-related quality of life, perceived health status, activity
      level, motivators, barriers, and program perceptions. FINDINGS: A small increase
      in level of activity from precancer to the current time (postrehabilitation) (z =
      -3.1, p < 0.01) was reported. Most and least helpful motivators emerged from the
      narrative data, resulting in the shared interpretation of "I have my life back."
      CONCLUSIONS: Program motivators were effective in helping cancer survivors
      maintain some increased activity and retain positive perceptions well after the
      completion of the program. IMPLICATIONS FOR NURSING: Survivors who complete a
      rehabilitation program retain a sense of restoration and caring, and some engage
      in physical activity over time. Adapting the program based on insights into the
      survivor perspective may assist oncology rehabilitation clinicians to promote
      optimum physical activity and sustain healthful change.

PMID- 24578088
TI  - Nutritional differences between a gluten-free diet and a diet containing
      equivalent products with gluten.
AB  - The gluten-free (GF) products market represents one of the most prosperous
      markets in the field of food and beverages in the immediate future. Historically,
      counselling for celiac disease has focused on the absence of gluten in foods,
      however the nutritional quality of GF foodstuffs is an important aspect to
      consider. The aim of the present work was to compare the nutritional composition
      of the 206 GF rendered products most consumed in Spain, against the composition
      of 289 equivalent foods with gluten, and to make a comparison between the diet
      including GF products and the same diet with equivalent products with gluten in a
      58 adult celiac population. The results of the present collaborative study
      pointed out differences in calorie, macronutrient, fiber, sodium, salt and
      cholesterol content between GF rendered and gluten-containing foodstuffs. Thus,
      calorie and nutrient intake in a GF diet is different when compared to its
      equivalent diet with gluten. Following a diet based on GF products could suppose
      a nutritional imbalance for celiac patients as well as for non-celiacs who follow
      a diet that includes many GF rendered foodstuffs. 

PMID- 24578089
TI  - The benefit of interleaved mathematics practice is not limited to superficially
      similar kinds of problems.
AB  - Most mathematics assignments consist of a group of problems requiring the same
      strategy. For example, a lesson on the quadratic formula is typically followed by
      a block of problems requiring students to use that formula, which means that
      students know the appropriate strategy before they read each problem. In an
      alternative approach, different kinds of problems appear in an interleaved order,
      which requires students to choose the strategy on the basis of the problem
      itself. In the classroom-based experiment reported here, grade 7 students (n =
      140) received blocked or interleaved practice over a nine-week period, followed
      two weeks later by an unannounced test. The mean test scores were greater for
      material learned by interleaved practice rather than by blocked practice (72 %
      vs. 38 %, d = 1.05). This interleaving effect was observed even though the
      different kinds of problems were superficially dissimilar from each other,
      whereas previous interleaved mathematics studies had required students to learn
      nearly identical kinds of problems. We conclude that interleaving improves
      mathematics learning not only by improving discrimination between different kinds
      of problems, but also by strengthening the association between each kind of
      problem and its corresponding strategy.

PMID- 24578091
TI  - The flanker effect does not reflect the processing of "task-irrelevant" stimuli:
      evidence from inattentional blindness.
AB  - It is often the case that stimuli (or aspects of a stimulus) are referred to as
      being "task-irrelevant." Here, we recount where this label originated and argue
      that the use of this label is at odds with the concept of "relevance" that has
      arisen in the contingent-capture literature. This is not merely a matter of
      labels, but a matter of inference: When people describe a flanker stimulus as
      being "task-irrelevant," they may be (and sometimes are) tempted to infer that
      the conditions that were studied in the flanker task generalize to other tasks
      and other types of stimuli. Here, we show that this generalization is not
      warranted. The flanker effect exists not because attention has failed at
      selecting only the target from the display, but rather, the effect arises
      precisely because attention succeeded at selecting target-like (i.e.,
      attentionally relevant) stimuli from the display. As a result, the flanker effect
      should not be used to infer how stimuli that are entirely unrelated to a
      participant's main task would be processed. We propose the use of a new
      terminology to replace this potentially misleading label.

PMID- 24578092
TI  - Conceptual response distance and intervening keys distinguish action goals in the
      Stroop color-identification task.
AB  - In previous studies, a physical response-distance effect was found in the two
      choice Stroop color-identification task, with the Stroop effect being larger when
      the two response keys were physically close together than when they were far
      apart. In the present study, we found a conceptual response-distance effect, with
      the Stroop effect being larger when the response keys were conceptually close
      (labeled as "5" and "6") than when they were conceptually far (labeled as "1" and
      "9"). Moreover, a response-distance effect due to pure physical distance was not
      evident; rather, the effect was found only when additional keys were placed
      between the two far response keys. These results are in agreement with a view
      that response keys are coded as action goals, with farther conceptual distance
      and additional keys helping distinguish the action goals. The results are
      difficult to reconcile with accounts that place emphasis on the physical
      separation of the effectors or their inanimate extensions. 

PMID- 24578090
TI  - How and why do infants imitate? An ideomotor approach to social and imitative
      learning in infancy (and beyond).
AB  - It has been proposed that already in infancy, imitative learning plays a pivotal
      role in the acquisition of knowledge and abilities. Yet the cognitive mechanisms
      underlying the acquisition of novel action knowledge through social learning have
      remained unclear. The present contribution presents an ideomotor approach to
      imitative learning (IMAIL) in infancy (and beyond) that draws on the ideomotor
      theory of action control and on recent findings of perception-action matching.
      According to IMAIL, the central mechanism of imitative and social learning is the
      acquisition of cascading bidirectional action-effect associations through
      observation of own and others' actions. First, the observation of the visual
      effect of own actions leads to the acquisition of first-order action-effect
      associations, linking motor codes to the action's typical visual effects. Second,
      observing another person's action leads to motor activation (i.e., motor
      resonance) due to the first-order associations. This activated motor code then
      becomes linked to the other salient effects produced by the observed action,
      leading to the acquisition of (second-order) action-effect associations. These
      novel action-effect associations enable later imitation of the observed actions.
      The article reviews recent behavioral and neurophysiological studies with infants
      and adults that provide empirical support for the model. Furthermore, it is
      discussed how the model relates to other approaches on social-cognitive
      development and how developmental changes in imitative abilities can be
      conceptualized. 

PMID- 24578093
TI  - Impact of spinal alignment and back muscle strength on shoulder range of motion
      in middle-aged and elderly people in a prospective cohort study.
AB  - PURPOSE: The relationship between spine and shoulder motion has not been well
      evaluated. The purpose of this study was to clarify the relationships among
      thoracic kyphosis and lumbar lordosis, spinal range of motion (ROM), spinal
      alignment and shoulder ROM. METHODS: Evaluation of spinal alignment was
      prospectively conducted in 317 subjects (114 males and 203 females, the average
      age: 67 years) who attended a public health checkup. Shoulder ROM with an angle
      meter and shoulder pain were evaluated. Thoracic kyphosis angle, lumbar lordosis
      angle, thoracic ROM, lumbar ROM and spinal inclination angle were measured using
      SpinalMouse((r)). The relationships of these factors with grip strength, back
      muscle strength, physical ability, osteoporosis and body mass index were examined
      and multivariate logistic regression analysis was performed to identify the risk
      factors for limited shoulder ROM. RESULTS: Limited shoulder flexion was found in
      35 patients (11 %) and limited abduction in 50 patients (16 %). In multivariate
      logistic regression analyses adjusted for age, shoulder pain and other
      parameters, increased thoracic kyphosis angle and increased spinal inclination
      angle were risk factors for limited shoulder flexion (p < 0.05). Increased
      thoracic kyphosis angle and weak back muscle strength were also determined as
      risk factors for limited shoulder abduction (p < 0.05). CONCLUSIONS: This study
      provides the first evidence that increased thoracic kyphosis, increased spinal
      inclination and weak back muscle strength are the risk factors for limited
      shoulder ROM. These results suggest that maintenance of spinal alignment and back
      muscle strength may be important for better shoulder ROM.

PMID- 24578095
TI  - A comparison of intravenous and intradiscal delivery of multipotential stem cells
      on the healing of injured intervertebral disk.
AB  - A major hurdle of cellular therapy for biological treatment of intervertebral
      disk (IVD) degeneration is the delivery method where current delivery methods are
      limited to intradiscal injection which can potentially cause further
      degeneration. Recent studies indicated that multipotential stem cells (MPSCs)
      from human umbilical cord blood home to injured sites and induce local
      therapeutic changes, thereby potentially addressing the drawbacks of direct
      delivery. We tested the effects of these cells on injured IVD using a mouse model
      of puncture-induced degeneration via two delivery methods. Caudal IVD underwent
      needle puncture, and MPSCs were injected indirectly (intravenously), or directly
      (intradiscally) into the nucleus pulposus. IVD were harvested for histological,
      gene and protein analysis after 14 weeks. Our finding showed limited homing
      ability of the MPSCs. However, regardless of delivery method, no engraftment or
      expansion of MPSCs was observed at the injured site. Contrasting to direct
      injection, intravenous injection neither improved the degeneration status, nor
      preserve disk height, however, both delivery methods increased glycosaminoglycan
      (GAG) protein and Acan gene expression relative to controls, suggesting possible
      paracrine effects. Identifying the mechanisms by which MPSCs act on endogenous
      IVD cells would provide insights into the potential of these cells to treat IVD
      injuries and degeneration.

PMID- 24578098
TI  - Deep brain stimulation in Parkinson's disease: motor effects relative to the MRI
      defined STN.
AB  - This study aims to evaluate the improvements of cardinal motor symptoms depending
      on the stimulation site relative to a standardized, reconstructed three
      dimensional MRI-defined subthalamic nucleus (STN.) This retrospective, clinical
      study includes 22 patients with idiopathic Parkinson's disease, who consecutively
      underwent bilateral subthalamic nucleus stimulation. Intraoperative
      microelectrode recording and clinical testing were performed. The location of the
      best stimulation site, found intraoperatively, and the positions of the active
      electrode contacts 12 months after the operation were correlated to a
      standardized, reconstructed three-dimensional MRI-defined STN. Further, the
      impact of the stimulation site on rigidity, tremor and akinesia was analysed.
      Significant improvement of the contralateral akinesia was observed if the
      intraoperative stimulation site was located more lateral and superior in the MRI
      STN. Furthermore, active electrode contacts located superior to or in the
      superior part of the MRI-STN had a significantly better effect on the tremor of
      the contralateral hand than in other locations inside the STN. For rigidity and
      akinesia, these correlations were statistically not significant. Although we
      found significantly better results for tremor suppression in superior and lateral
      aspects of the STN, for overall clinical improvement, several patients fared
      better with randomly distributed stimulation sites in medial, posterior or
      inferior parts of the MRI-defined STN. Locations of stimulation sites with the
      best improvements of motor symptoms were distributed randomly throughout the
      whole MRI-defined STN, indicating that MRI-based targeting alone is not
      sufficient, but intraoperative clinical testing is necessary to determine the
      optimal stimulation site for each individual patient.

PMID- 24578096
TI  - White matter development and early cognition in babies and toddlers.
AB  - The normal myelination of neuronal axons is essential to neurodevelopment,
      allowing fast inter-neuronal communication. The most dynamic period of
      myelination occurs in the first few years of life, in concert with a dramatic
      increase in cognitive abilities. How these processes relate, however, is still
      unclear. Here we aimed to use a data-driven technique to parcellate developing
      white matter into regions with consistent white matter growth trajectories and
      investigate how these regions related to cognitive development. In a large sample
      of 183 children aged 3 months to 4 years, we calculated whole brain myelin volume
      fraction (VFM ) maps using quantitative multicomponent relaxometry. We used
      spatial independent component analysis (ICA) to blindly segment these
      quantitative VFM images into anatomically meaningful parcels with distinct
      developmental trajectories. We further investigated the relationship of these
      trajectories with standardized cognitive scores in the same children. The
      resulting components represented a mix of unilateral and bilateral white matter
      regions (e.g., cortico-spinal tract, genu and splenium of the corpus callosum,
      white matter underlying the inferior frontal gyrus) as well as structured noise
      (misregistration, image artifact). The trajectories of these regions were
      associated with individual differences in cognitive abilities. Specifically,
      components in white matter underlying frontal and temporal cortices showed
      significant relationships to expressive and receptive language abilities. Many of
      these relationships had a significant interaction with age, with VFM becoming
      more strongly associated with language skills with age. These data provide
      evidence for a changing coupling between developing myelin and cognitive
      development.

PMID- 24578099
TI  - Carotid artery occlusion for the treatment of symptomatic giant carotid
      aneurysms: a proposal of classification and surgical protocol.
AB  - Giant intracranial aneurysms are rare disorders that represent only 5% of all
      intracranial aneurysms; they have a wide variety of presentations including
      rupture, embolic effects, and mass effect symptoms that can mislead the diagnosis
      to tumors rather than aneurysms. Their treatment is difficult and carries higher
      morbidity and mortality than usual aneurysms due to their complex nature. This
      study involved retrospective analysis of data of 28 patients, managed between
      2006 and 2012, suffering from giant internal carotid artery (ICA) aneurysms with
      various presenting symptoms, none of which was hemorrhage. They were all
      evaluated by BOT prior to any intervention; they were subjected to various
      treatment strategies including selective coiling, parent artery occlusion with or
      without bypass, aneurysm trapping with or without bypass, and patients were
      followed for a period ranging from 6 months to 5 years. Out of 26 patients with
      giant aneurysms with mass effects, 16 patients showed full recovery (61.5 %), 5
      showed partial improvement (19.2 %), and 5 showed no change in mass effect
      symptoms (19.2 %). One patient died (3.5 %). Symptoms such as TIA or epistaxis
      showed complete recovery. This study shows that a well-designed protocol aiming
      at parent artery sacrifice will yield good to excellent results in managing ICA
      giant aneurysms, and it also shows that parent artery sacrifice is superior to
      other forms of treatment of these lesions regarding recurrence rates, morbidity,
      and mortality.

PMID- 24578100
TI  - Direct electrical stimulation of the optic radiation in patients with covered
      eyes.
AB  - Direct electrical stimulation (DES) of the optic radiation (OR) during an awake
      tumor resection has been repeatedly reported. In all cases, visual function
      monitoring was performed in patients with open eyes which were looking at a
      picture. We report a new modification of the standard method, OR stimulation in
      patient with closed and covered eyes. To the best of our knowledge, this method
      was not presented before. According to our first experience, this methodology may
      be in some cases a potentially more sensitive form of neuromonitoring than the OR
      stimulation in patients with open eyes, as the phosphenes elicited by DES may be
      more distinct in patients with covered eyes. The technique is discussed, and a
      literature review on intraoperative identification of the OR is presented as
      well. However, a future prospective study is needed to confirm the relevance of
      our finding. 

PMID- 24578101
TI  - The legacy of Ladislau Steiner (1920-2013): the neurosurgeon who won the heart of
      the world : Ad astra per aspera.

PMID- 24578103
TI  - Evaluation of the URiSCAN super cassette ACR semiquantitative urine dipstick for
      microalbuminuria screening.
AB  - BACKGROUND: Microalbuminuria tests are used as screening tools for diseases, such
      as diabetic nephropathy, cardiovascular disease, and hypertension. The purpose of
      this study was to evaluate the utility of a newly introduced semiquantitative
      urine dipstick, URiSCAN Super cassette ACR (URiSuper-ACR [where ACR is
      albumin/creatinine ratio]; YD Diagnostics Corp., Korea), as a screening tool for
      microalbuminuria. METHODS: Albumin and creatinine levels in randomly selected
      spot urine samples of 1,040 patients were semiquantitatively measured using
      URiSuper-ACR. Results using URiSuper-ACR system were compared to measurements
      obtained by quantitative analyzer. We also calculated diagnostic sensitivity,
      specificity, precision, linearity, and categorical concordance rates for the
      diagnosis of microalbumiuria using this system. Furthermore, we performed
      interference tests using standard controls to evaluate possible influence of
      various factors. RESULTS: URiSuper-ACR test showed 88.8% and 86.3% sensitivity
      and 90.1% and 93.8% specificity for albumin concentration and ACR, respectively.
      It also showed 91.1% and 92.6% positive predictive values and 87.6% and 88.5%
      negative predictive values, respectively. The concordance rate between URiSuper
      ACR and quantitative method for albumin and creatinine concentration within the
      same category were 78.4% and 67.1%, respectively, and for the +/-1 category were
      98.8% and 99.5%, respectively. For ACR, an 80.0% concordance rate was seen within
      the same category. The within-run coefficients of variation (CVs) were 3.0~15.4%
      and 5.2~23.5% for albumin and creatinine, respectively, showing good linearity.
      In interference tests, no interference was observed except for cases with high
      specific gravity. CONCLUSIONS: URiSuper-ACR showed good diagnostic performance
      for the detection of microalbuminuria and may be a useful screening test in
      clinical laboratories.

PMID- 24578104
TI  - Exploring occupation roles of hospice family caregivers from Maori, Chinese and
      Tongan ethnic backgrounds living in New Zealand.
AB  - A major challenge to occupational therapists working in palliative care is
      determining the best ways to help family caregivers who are caring for family
      members. The purpose of this study was to explore palliative caregiver
      occupations among Maori, Chinese and Tongan ethnicities. Six informants
      participated, one woman and one man from each ethnic group. In each of their
      homes, informants were asked to discuss what it was like caring for their dying
      family member. The occupational themes resulting from these interviews were food
      preparation, spirituality and family gathering. Therapists need to be aware of
      the differences in how people care for family members within their ethnicity.
      Implications are that occupational therapists can help families identify
      activities important to them within the main occupational themes: different types
      of foods and their preparations, various ways to express spirituality and how
      families gather together members of their extended family. Further, clinicians
      need to take on the role of a "not-knowing" but curious health-care provider in
      order to meet the needs of caregivers. The limitation was the small number of
      participants who all lived in one geographic area. Future studies should include
      a wider group of ethnicities.

PMID- 24578105
TI  - Detecting and correcting for family size differences in the study of sexual
      orientation and fraternal birth order.
AB  - The term "fraternal birth order effect" denotes a statistical relation most
      commonly expressed in one of two ways: Older brothers increase the odds of
      homosexuality in later born males or, alternatively, homosexual men tend to have
      more older brothers than do heterosexual men. The demonstrability of this effect
      depends partly on the adequate matching of the homosexual and heterosexual study
      groups with respect to mean family size. If the homosexual group has too many
      siblings, relative to the heterosexual group, the homosexual group will tend to
      show the expected excess of older brothers but may also show an excess of other
      sibling-types (most likely older sisters); if the homosexual group has too few
      siblings, it will tend not to show a difference in number of older brothers but
      instead may show a deficiency of other sibling-types (most likely younger
      brothers and younger sisters). In the first part of this article, these
      consequences are illustrated with deliberately mismatched groups selected from
      archived data sets. In the second part, two slightly different methods for
      transforming raw sibling data are presented. These are intended to produce family
      size-corrected variables for each of the four original sibling parameters (older
      brothers, older sisters, younger brothers, and younger sisters). Both versions
      are shown to render the fraternal birth order effect observable in the
      deliberately mismatched groups. In the third part of the article, fraternal birth
      order studies published in the last 5 years were surveyed for failures to find a
      statistically significant excess of older brothers for the homosexual group. Two
      such studies were found in the nine examined. In both cases, the collective
      findings for older sisters, younger brothers, and younger sisters suggested that
      the mean family size of the homosexual groups was smaller than that of the
      heterosexual comparison groups. Furthermore, the individual findings for the four
      classes of siblings resembled those for the present experimentally mismatched
      groups in which the mean family size of the homosexual group was significantly
      smaller. This illustrates the necessity of comparing groups on measures of mean
      family size and removing this confound in some way when those means are markedly
      different.

PMID- 24578102
TI  - A polymorphism in TLR2 is associated with arterial thrombosis in a multiethnic
      population of patients with systemic lupus erythematosus.
AB  - OBJECTIVE: Thrombosis is a serious complication of systemic lupus erythematosus
      (SLE). Studies that have investigated the genetics of thrombosis in SLE are
      limited. We undertook this study to assess the association of previously
      implicated candidate genes, particularly Toll-like receptor (TLR) genes, with
      pathogenesis of thrombosis. METHODS: We genotyped 3,587 SLE patients from 3
      multiethnic populations for 77 single-nucleotide polymorphisms (SNPs) in 10
      genes, primarily in TLRs 2, 4, 7, and 9, and we also genotyped 64 ancestry
      informative markers (AIMs). We first analyzed association with arterial and
      venous thrombosis in the combined population via logistic regression, adjusting
      for top principal components of the AIMs and other covariates. We also subjected
      an associated SNP, rs893629, to meta-analysis (after stratification by ethnicity
      and study population) to confirm the association and to test for study population
      or ethnicity effects. RESULTS: In the combined analysis, the SNP rs893629 in the
      KIAA0922/TLR2 region was significantly associated with arterial thrombosis
      (logistic P = 6.4 * 10(-5) , false discovery rate P = 0.0044). Two additional
      SNPs in TLR2 were also suggestive: rs1816702 (logistic P = 0.002) and rs4235232
      (logistic P = 0.009). In the meta-analysis by study population, the odds ratio
      (OR) for arterial thrombosis with rs893629 was 2.44 (95% confidence interval 1.58
      3.76), without evidence for heterogeneity (P = 0.78). By ethnicity, the effect
      was most significant among African Americans (OR 2.42, P = 3.5 * 10(-4) ) and
      European Americans (OR 3.47, P = 0.024). CONCLUSION: TLR2 gene variation is
      associated with thrombosis in SLE, particularly among African Americans and
      European Americans. There was no evidence of association among Hispanics, and
      results in Asian Americans were limited due to insufficient sample size. These
      results may help elucidate the pathogenesis of this important clinical
      manifestation.

PMID- 24578106
TI  - Lisping and male homosexuality.
AB  - The present study examined the popular stereotype that gay men lisp by evaluating
      to what extent listeners associated dental or frontal articulation/lisping with
      gayness. Fifteen heterosexual males and 15 heterosexual females listened to 275
      samples of read speech and judged the sexual orientation of the speakers. A total
      of 175 of the samples were of homosexual men, 74 (42.3 %) of which had been
      identified with lisping in a previous study; 100 were of heterosexual men, 18 (18
      %) of which had been identified with lisping previously. Based on the ratings of
      the listeners of the present study, lisping speakers were significantly more
      often judged to be homosexual. This was true for the group as a whole as well as
      for the subgroup of homosexual and heterosexual men separately. Furthermore,
      there was no significant gender difference with respect to associating lisping
      with gayness. Male and female judges associated lisping with gayness to a similar
      degree. Additional analysis showed that overall 56.2 % of the time the judges
      were correct in their judgment of the speakers' sexual orientation. The results
      of this study confirmed previous preliminary findings that suggested that frontal
      or dental articulation/lisping is a feature that listeners associate with
      gayness. The reason for this association remains to be clarified. 

PMID- 24578107
TI  - [Percutaneous treatment of unstable spine fractures - OP video and results from
      over 300 cases].
AB  - Minimally invasive surgery for vertebral fractures results in less approach
      related morbidity, decreased postoperative pain, and rapid mobilisation of
      patients. Such procedures can be performed even in elderly patients. However,
      along with the many advantages, minimally invasive procedures are technically
      demanding, require sophisticated tools, and there is a learning curve for
      surgeons. Intraoperative visualisation is often possible only radiologically, and
      implants are generally much more expensive. Using the data from over 300 unstable
      vertebral fracture cases treated over the past 3.5 years, we have developed a
      differentiated treatment concept, depending on the age of the patient and the
      fracture characteristics. Unstable fractures with involvement of the posterior
      edge are stabilised from posterior, percutaneously with a fixator. In patients
      under 60 years, monoaxial screws with inserted rods (top loading) are used, with
      which distraction and restoration of lordosis are also possible. Patients over 60
      years are treated percutaneously with a polyaxial sextant system with rods
      inserted to avoid avulsion of the pedicle screws from the vertebral body. To
      avoid cutting through the vertebra, the fenestrated screws can be augmented with
      cement. The operation technique is demonstrated by a video. 

PMID- 24578108
TI  - [Consequences of "quality offensives" and the services of free-based physicians
      in hospitals].

PMID- 24578109
TI  - [Fractures of the neck of the femur in younger patients (15-50 years old).
      Outcome 4 years after surgery].
AB  - INTRODUCTION: Traumatic fractures of the neck of the femur are rare injuries in
      younger patients between 15 and 50 years old. The short-term and long-term
      complications may cause substantial problems, in particular non-union and
      avascular necrosis (AVN) of the head of the femur. In the literature (and from
      some experts) the impression is occasionally given that there might be "proven"
      successful therapeutic procedures. METHODS: For this purpose we retrospectively
      analysed follow-up-data from our own patients in the years 2003-2007 and compared
      them with the literature. We identified 23 of a total of 376 patients with a
      femoral neck fracture as a cohort being younger than 50 years. 17 of those 23
      patients were treated with an internal fixation. We were able to collect and
      analyse complete clinical and radiological data of 11 of these 17 patients 4.2
      years after surgery. RESULTS: The mean interval between accident and surgery was
      22 hours. Only one of the patients developed an AVN after internal fixation of
      the fracture and was implanted a total hip replacement 18 months postoperatively.
      There was no non-union of the femoral neck The clinical outcome after 4.2 years
      was very good. The mean Harris Hip Score was 95 points (of a max. of 100 pts.).
      CONCLUSIONS: The osteosynthesis of femoral neck fractures in younger patients
      showed good results and a low risk of AVN and non-union. Therefore the internal
      fixation of the femoral neck fracture should be preferred for the younger
      patients instead of a primary total hip replacement.

PMID- 24578110
TI  - [A new anatomical wing plate for osteoporotic acetabular fractures: biomechanical
      testing and first clinical experience].
AB  - BACKGROUND: Acetabular fractures are rare injuries, but there is an increasing
      number of elderly people with ventral medial instability in cases of central
      subluxation of the femoral head in osteoporotic acetabular fractures. Common
      plate osteosynthesis cannot enable medial support of the quadrilateral surface.
      The new "acetabular wing plate" is anatomically shaped to fix the arcuate line
      and the quadrilateral surface. The plate pushes the femoral head back to lateral.
      The aim of this study was the biomechanical comparison with common plate concepts
      before clinical use of the new implant. METHODS: For biomechanical testing eight
      artificial fracture models of the pelvis with anterior column fractures were
      used. They were implemented into a set-up of a one-leg stand model in the
      material test machine. Cyclical movements with axial pressure to the sacrum up to
      250 N were given to the model. Fracture gap movement was measured with an
      optoelectronic 3D camera measuring system. In all pelvic models all screw holes
      were drilled by use of drill guides before first mechanical loading. The
      measurements were randomly done first with the new acetabular wing plate or with
      the pelvic low profile plate. Absolute and relative fracture gap movement and
      movements of the pelvic fragments were measured as well. RESULTS: The fracture
      gap movement and the fragment rotation were comparable in both groups. There was
      a slightly higher stability in the group of the acetabular wing plate but without
      statistical significance. In the pelvic low profile group two screw loosenings
      were found, but the models were able to be tested also with the acetabular wing
      plate. The new plate was clinically used in the first eight patients due to the
      good biomechanical results. In all cases the osteosyntheses were done by use of
      the Stoppa approach and the first window of the ilioinguinal approach.
      Application of the plate was mostly easy, the plate was also used as a reduction
      tool. Postoperative controls show anatomic reduction and correct implant position
      in all eight cases. The three month follow-up examinations confirm the continuing
      good reduction during fracture healing with the acetabular wing plate.

PMID- 24578111
TI  - [Unrecognised dissociation of the bipolar hip prosthesis Avantage(r) (Biomet(r))
      after closed reduction of a dislocation: a rare complication].
AB  - An 84-year-old female patient was admitted to our emergency department with a
      periprosthetic fracture of the left femur with an implanted Avantage prosthesis
      (Biomet(r)). Conventional X-ray images revealed besides the fracture a
      lateralisation of the prosthesis stem. An additional CT scan showed a
      dissociation of the polyethylene inlay from the head of the prosthesis which took
      place 3 years ago in the course of a closed reposition of a postoperative
      luxation. This event shows the relevance of a precise analysis of X-ray images
      after reposition regarding the exact articulation of the different prosthesis
      components. 

PMID- 24578112
TI  - [Avulsion of the proximal hamstring origin - report of 6 cases].
AB  - Proximal hamstring origin avulsions are rare injuries. A common cause for this
      kind of injury is a trauma with the hamstring in overextension and simultaneously
      forced hip flexion and knee extension. We report on 6 cases, 5 with an acute
      rupture of the hamstring origin and one case with a delayed presentation in our
      emergency room. In 3 cases the injury was related to sport activity, the other 3
      are related to accidents during work. None of these patients took part in
      competitive sports. One case was reported 8 weeks after trauma with an MRI
      performed one week before. Due to the low functional deficits conservative
      treatment was preferred. In all of the acute injuries open refixation was done
      within the first two weeks after trauma using 2-3 suture anchors. Postoperative
      mobilisation was done with partial weight bearing. Active knee flexion against
      gravity was not started until six weeks postoperative. All patients who had
      surgery achieved good results 3-28 months after surgery. They suffered from only
      little pain (VAS1-2) and had good movement ability. Sport activities were reduced
      in 3 cases, 2 patients returned to pre-injury sport levels. All patients were
      able to perform one-legged squats. In the evaluated LEFS (Lower Extremity
      Functional Scale) 75.6/80 points were achieved (72-79). There were no severe
      complications within this case study. It is important to distinguish proximal
      hamstring origin avulsions from the majority of hamstring muscle injuries. If the
      avulsion is treated with surgery, refixation should be performed within the first
      weeks to prevent the sciatic nerve from being bound in scar tissue with a
      consecutive high risk of injury during mobilisation of the tendon. 

PMID- 24578113
TI  - [Post-surgical gout after total hip arthroplasty - a case report].
AB  - The following report deals with the case of a post-surgical gout after total hip
      arthroplasty. Before surgery, the patient was diagnosed with hyperuricaemia.
      Following the procedure, the patient developed superinfected gout tophi and
      several joint infections. Multiple surgeries were necessary to control the
      illness and to finally heal the infection. This study stresses pre-surgical
      hyperuricaemia as a severe illness and demonstrates a positive medical history of
      gout as a risk for post-surgical precipitation of uric acid. We hope to increase
      the surgeon's awareness of post-surgical gout symptoms in order to ensure
      adequate patient care. 

PMID- 24578114
TI  - [Epidural injection shows no advantages over oral medication and physiotherapy in
      the treatment of sciatica, irrespective of the duration of symptoms].
AB  - BACKGROUND: The study presented here investigated the short-term effectiveness of
      one-off lumbar caudal epidural injection (EI) in sciatica in relationship to the
      reported duration of pain. MATERIALS AND METHODS: This retrospective analysis
      involved 106 consecutive in-patients who received either conservative treatment
      (Group I) or an additional EI on the first day of their treatment (Group II).
      Both groups were divided according to the duration of symptoms at the time of
      admission (less than three months, or more than six months). Propensity score
      matching was performed for the whole collective and the resulting subgroups. This
      incorporated gender, age and pain intensity at the time of admission. The target
      parameter were changes on a visual analogue scale (VAS) of pain intensity on days
      D1, D3, and D10 depending on the respective treatment. A routine evaluation of
      the mental variables anxiety, depression and somatisation was performed as part
      of the examination upon admission and their relationship to the success of
      treatment was later assessed. RESULTS: The mean age of the patients was 61.7 (+/-
      11.6) in Group I and 63.6 (+/- 13.6) in Group II. 59 % of the patients were
      female (n = 63). The Lasegue sign was prevalent in 45 % of Group I and 51 % of
      Group II. The intensity of pain on the day of admission was similar in both
      groups (7.0 +/- 1.0 for Group I, 6.7 +/- 1.8 for Group II). The length of stay on
      the ward was also similar in both groups (10.2 +/- 3.9 and 9.4 +/- 3.7 d,
      respectively). It was found that, independent of the duration of symptoms,
      injection treatment was significantly more effective than conservative treatment
      only in the early stages (D1 and D3, p < 0.001). No differences could be found in
      the expression of these mental variables between treatment groups, as these
      factors showed no influence on the results of therapy. CONCLUSIONS: In the
      context of acute treatment a once only lumbar caudal epidural injection
      represents at most a short-term effectiveness for the therapy of sciatica. The
      results presented here indicate that neither the duration of symptoms nor the
      measured psychometric variables show any effect on the success of therapy.

PMID- 24578115
TI  - [Structured assessment for orthopaedic patients - method, results, and diagnostic
      potential].
AB  - BACKGROUND: Review of medical records demonstrates a moderate to low correlation
      (r = 0.57 to 0.22) between daily limitations and symptoms based upon patient
      history. This correlation could be improved with the ideal questionnaire which
      would assess patients using the same questions with the same response options in
      the same order. Therefore, a simple patient questionnaire for orthopaedic
      patients was developed and validated to assess 10 symptoms, 12 limitations of
      daily life and patients' well-being. The concept was to provide a universal
      questionnaire that could be used for all patients and provide the basis for a
      structured assessment that would then provide standardised and comparable patient
      information. Additional localisation of symptoms would allow a differential
      diagnosis. For example, pain in the groin/thigh while standing and walking may be
      caused by osteoarthritis of the hip or osteochondrosis of the lumbar spine.
      Further physical investigation and diagnostic imaging may lead to the diagnosis.
      PATIENTS AND METHODS: This method was employed as part of routine quality control
      from November 2006 to October 2008 by two orthopaedic surgeons in their
      outpatient clinic in a tertiary health care hospital. Structured assessment was
      performed in all patients regardless of their pathology (hip, knee, shoulder,
      cervical spine, lumbar spine, foot) or situation (before/after surgery,
      conservative therapy). The completeness, symptom score, daily limitation score,
      and well-being as well as the relationships between symptom score, daily
      limitation score, and well-being were calculated. Answers regarding walking
      capacity and effective walking capacity could be compared. Several patients with
      combined orthopaedic pathologies were closely analysed. RESULTS: Data of 2642
      structured assessments in 1777 patients (957 women, 53.9 %) were evaluated. The
      average age was 64.4 years. The data completeness on the front page was 96.2 and
      86.3 % on the back page. The mean value for symptoms (daily limitations) was
      34.31 (27.45), and the median was 32.5 (25.0). The distributions of the symptom
      score and daily limitation score were asymmetrical; 80 % of the patients were
      below 50 and 38, respectively. Well-being was excellent in 21.4 %, good in 24 %,
      moderate in 24.2 %, poor in 11.4 %, and very poor in 16.7 %. The main symptom was
      pain on movement/walking, with an average of 60.32. The symptom score, daily
      limitation score, and well-being were found to have a correlation to each other
      (Spearman's r between 0.55 and 0.63). Thirty-nine patients reported an inability
      to walk, although 36 could walk in the office (1 had paraplegia and 2 had
      paraparesis caused by lumbar stenosis). Combined pathologies in orthopaedic
      patients were found for cervical-shoulder, lumbar-hip, and lumbar-knee
      pathologies. CONCLUSIONS: A routine structured assessment can be performed with
      extra effort. A structured assessment provides patient information in a
      standardised form so that such information can be compared as well as allow a
      differential diagnosis. It is possible that answers to the questionnaire
      represent patients' subjective assessment rather than reality.

PMID- 24578116
TI  - [Patella dislocation: an algorithm for diagnostic and treatment considering the
      rotation].
AB  - BACKGROUND: Patella dislocation and re-dislocation are common diseases. Although
      patella dislocation is frequent, it always poses a challenge concerning
      diagnostics and therapy. Mixed forms of pathological disorder in the
      patellofemoral joint make the analysis of the malalignment and the choice of the
      correct treatment more difficult. MATERIAL AND METHODS: By reviewing the
      available literature of the last few years and taking into account considerations
      concerning the malalignment, an overview of the necessary diagnostics can be
      given. Radiographs and MRI are essential parts of the diagnostics after a
      traumatic patella dislocation. After re-dislocation, more extensive diagnostics
      are required to determine all pathological aspects of the malalignment. In this
      situation, a CT scan for measuring the torsion of the femur and the tibia as well
      as the TT-TG distance (tibial tubercle - trochlea groove), and the full weight
      bearing long leg standing radiograph are part of the fundamental diagnostics.
      RESULTS: The results that are presented in the literature provide some
      indications for a successful treatment. In consideration of the thorough analysis
      of the malalignment, the torsional correction of the femur and/or the tibia gains
      a new importance in the patellofemoral joint. The presented algorithm for
      diagnostics and treatment should make the decision for the best treatment easier.
      CONCLUSION: The proposed algorithm for diagnostics and treatment is only
      partially founded on evidence-based results. Moreover, it takes into
      consideration reflections concerning the biomechanics of the patellofemoral joint
      and the realignment of this joint.

PMID- 24578117
TI  - [Plantar pressure platform as clinical assesment tool in the analysis of foot
      posture with the foot posture index].
AB  - BACKGROUND: The foot posture index is a static measurement that splits up the
      foot posture into neutral, pronatus and supinatus. However, the relation between
      the foot posture and the plantar pressure standards is not well known. For this,
      the objective of this research is to check the relationship between the foot
      posture and plantar pressure standard. SUBJECTS AND MATERIAL: 144 participants
      (101 women and 43 men), mean age 25.4 +/- 6.3 years, were measured for the FPI.
      The pedobarometric measurement was made with the plantar pressure platform, we
      measured total surface (cm2), mean pressure (kPa) and maximum pressure (kPa),
      these measurements were correlated with the FPI measurements. RESULTS: 288 feet
      were analysed with regard to the correlation between point 5 of FPI (medial arch
      height) and the plantar surface total area (p = 0.038): lower arch height and
      supinated foot are related to the maximum pressure points with p = 0.029. The
      total contact surface can be determined with the final score of the FPI, the
      scores of FPI 3, 5 and 6 FPI (r2 = 0.059, p < 0.001) with a 5.9 % prediction.
      CONCLUSION: The supinatus foot is correlated statistically significantly through
      the maximum pressure and the plantar surface with the pronatus foot.

PMID- 24578118
TI  - [Therapy of degenerative and posttraumatic rotator cuff lesions].
AB  - The prevalence of rotator cuff lesions is age-dependent and up to 19-32 % for
      full-thickness ruptures and 13-32 % for partial-thickness lesions respectively.
      The therapy of partial-thickness ruptures should be considered in accordance with
      the articular, bursal or intratendinous location of the lesion. The therapy of
      full-thickness ruptures should be applied in accordance with topography and area
      of defect, retraction, atrophy and fatty infiltration. These parameters are
      considered to be important prognostic factors for the intraoperative
      repairability and the success of the surgery. Symptomatic or chronically
      progredient partial-thickness lesions as well as full-thickness lesions should
      generally be treated by means of surgical reconstruction. No current scientific
      consensus exists regarding improved clinical outcome data after the surgical
      approach in mini-open or arthroscopic technique. Both procedures should meet the
      requirements of the Gerber criteria for rotator cuff reconstruction: high primary
      stability, reduction of micro-movements, minimized approach associated morbidity
      and persisting stability to enable the fibroblastic tendon-to-bone healing.
      Current studies revealed a potential improvement of the tendon-to-bone healing by
      the application of several biologic augmentations. At the moment, these additive
      procedures can be applied in revision situations and for complex rotator cuff
      lesions with low tendon quality. No high-level in-vivo investigations concerning
      the human shoulder exist in the current literature that show evidence-based
      improvements by the additively applied biologic augmentations for rotator cuff
      repair. 

PMID- 24578119
TI  - A genetic counseling intervention to facilitate family communication about
      inherited conditions.
AB  - This paper describes the development and implementation of the first intervention
      to facilitate family communication of genetic information based on a genetic
      counseling model of practice. The intervention is telephone-based and therefore
      designed to complement face-to-face genetic counseling consultations. It was
      developed by firstly reviewing the literature and a model of genetic counseling
      practice, leading to definition of seven core principles underpinning the
      intervention. A counseling framework based on these principles was developed
      through iterative role playing and review, tested for consistency with good
      practice and piloted on ten study participants. It was found to be feasible to
      implement and consistent with good genetic counseling practice. Implementation
      included training of the genetic counselors who would deliver the intervention as
      part of a randomized controlled trial. Noteworthy deviations from good genetic
      counseling practice were observed, with unexpected additional insights into the
      'black box' of genetic counseling that may have wider implications and would
      benefit from further investigation. The intervention is currently being evaluated
      in a randomized controlled trial, to assess its impact on the number of family
      members attending genetic services.

PMID- 24578120
TI  - Traditional roles in a non-traditional setting: genetic counseling in precision
      oncology.
AB  - Next generation sequencing technology is increasingly utilized in oncology with
      the goal of targeting therapeutics to improve response and reduce side effects.
      Interpretation of tumor mutations requires sequencing of paired germline DNA,
      raising questions about incidental germline findings. We describe our experiences
      as part of a research team implementing a protocol for whole genome sequencing
      (WGS) of tumors and paired germline DNA known as the Michigan Oncology Sequencing
      project (MI-ONCOSEQ) that includes options for receiving incidental germline
      findings. Genetic counselors (GCs) discuss options for return of results with
      patients during the informed consent process and document family histories. GCs
      also review germline findings and actively participate in the multi-disciplinary
      Precision Medicine Tumor Board (PMTB), providing clinical context for
      interpretation of germline results and making recommendations about disclosure of
      germline findings. GCs have encountered ethical and counseling challenges with
      participants, described here. Although GCs have not been traditionally involved
      in molecular testing of tumors, our experiences with MI-ONCOSEQ demonstrate that
      GCs have important applicable skills to contribute to multi-disciplinary care
      teams implementing precision oncology. Broader use of WGS in oncology treatment
      decision making and American College of Medical Genetics and Genomics (ACMG)
      recommendations for active interrogation of germline tissue in tumor-normal dyads
      suggests that GCs will have future opportunities in this area outside of research
      settings. 

PMID- 24578121
TI  - Genetic counseling graduate student debt: impact on program, career and life
      choices.
AB  - The cost of education is rising, increasing student financial aid and debt for
      students pursuing higher education. A few studies have assessed the impact of
      student debt in medicine, physical therapy and social work, but little is known
      about the impact of student debt on genetic counseling students and graduates. To
      address this gap in knowledge, a web-based study of 408 recent alumni of genetic
      counseling programs in North America was conducted to assess the impact of
      student debt on program, career and life choices. Over half (63 %; n = 256/408)
      of the participants reported that loans were extremely important in their ability
      to attend their training program, with most using subsidized loans no longer
      available to current graduate students. While participants were generally
      satisfied with their genetic counseling education, 83 % (n = 282/342) of
      participants with student debt reported feeling burdened by their debt, which had
      a median of $40,000-$50,000. This debt is relatively close to the median starting
      salary reported by survey participants ($45,000-$50,000), breaching the "20-10
      rule" that states student debt should not exceed 20 % of annual net income. In
      response to this critical issue, we propose recommendations for the genetic
      counseling field that may help alleviate student debt impact and burden.

PMID- 24578122
TI  - Pneumonectomy for node-positive non-small cell lung cancer: can it be a treatment
      option for N2 disease?
AB  - OBJECTIVE: The feasibility of multimodality therapy in patients with node
      positive non-small cell lung cancer (NSCLC) requiring pneumonectomy and the role
      of pneumonectomy in N2 disease remain controversial. This study evaluated
      outcomes in patients with node-positive NSCLC undergoing pneumonectomy in a
      community hospital. METHODS: Perioperative and long-term outcomes of 37 patients
      with node-positive (pN1-2) NSCLC undergoing pneumonectomy from September 1994 to
      April 2010 as a clinical practice were retrospectively analyzed. RESULTS: Twenty
      patients received induction therapy, and 17 received preoperative chemoradiation
      (30-40 Gy). Fifteen patients and 22 patients underwent right and left
      pneumonectomy, respectively. A postoperative complication occurred in 8 patients.
      In-hospital mortality occurred in 1 patient. Induction therapy did not increase
      the operative risk including operative time, blood loss and postoperative
      complications. Nineteen patients were given a diagnosis of pN2. Although 7 bulky
      N2 patients and 10 multi-station N2 patients were included, 5-year overall
      survival was 34.3 % in pN1 and 28.0 % in pN2 (p = 0.998), respectively. Twenty
      three patients received additional postoperative therapy. Five patients died
      within 3 months postoperatively due to distant metastases. Induction therapy and
      laterality did not influence survival. Extended resection, such as vagus nerve or
      chest wall resection, predicted an unfavorable outcome in multivariate analysis
      (Hazard ratio 2.81, p = 0.032). CONCLUSIONS: The safety and acceptable long-term
      outcome of pneumonectomy as a general clinical practice were shown for both pN1
      and pN2 patients with various preoperative or postoperative therapies. Extended
      resection due to the extrapleural or extranodal involvement of tumor was an
      unfavorable prognostic factor.

PMID- 24578123
TI  - Psychosocial predictors in consideration of cosmetic surgery among women.
AB  - BACKGROUND: This study aimed to analyze the influence of psychosocial factors on
      the consideration of cosmetic surgery. The authors hypothesized that the
      internalization of thin ideals and social comparisons mediate the relationship
      between media pressure, family and peer influence (appearance conversations,
      perception of teasing, and peer attributions), and the desire to pursue cosmetic
      surgery. METHODS: The study participants were 429 Italian women (mean age, 33
      years). They completed a questionnaire containing the Appearance Conversations
      With Friends Scale, the Perception of Teasing Scale for Friends, the Peer
      Attribution Scale, the "Pressure and Internalization-General" subscales of the
      Sociocultural Attitudes Towards Appearance Questionnaire-3, the Feedback on
      Physical Appearance Scale, the Physical Appearance Comparison Scale, and the
      "Consider" subscale of the Acceptance of Cosmetic Surgery Scale. Hierarchical
      linear regression was performed. RESULTS: The results indicated that media
      pressure and appearance conversations with peers predicted the outcome variable
      through the full mediation of internalization of thin ideals. The relation
      between peer attributions and interest in cosmetic surgery was partially mediated
      by internalization of thin ideals. Although social comparison was significantly
      related to both sociocultural variables and consideration of cosmetic procedures,
      it was not a significant mediator of this relationship. Neither family influence
      nor perception of teasing predicted the outcome variable. CONCLUSIONS: Overall,
      these results provide important information about the factors implicated in the
      consideration of cosmetic surgery by women. This research confirms that cosmetic
      surgeons need to adopt a base psychological approach. 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- 24578124
TI  - Bronchopulmonary dysplasia: clinical perspective.
AB  - Since Northway's original description of BPD almost 45 years ago, the clinical
      presentation of BPD has evolved into a disease process, which mostly involves
      extremely premature infants. This new form of BPD is the result of multiple
      antenatal and postnatal factors that can cause injury to the developing lung
      leading to altered alveolar and vascular development. Over the years, there has
      been considerable increase in knowledge of factors that contribute to the
      development of BPD. This has led to different strategies for prevention as well
      as management of BPD. Some of these strategies have been successful and have
      withstood the test of clinical trials, such as vitamin A supplementation, post
      natal steroids, caffeine, and volume targeted ventilation. The evidence for other
      interventions has been weak or negative. With better understanding of the complex
      and multifactorial pathogenesis of BPD, it is quite clear that any single therapy
      is very unlikely to eliminate this problem unless it reduces prematurity. Further
      development in prevention and treatment of BPD will likely need a multi-pronged
      strategy with novel therapeutic agents acting at various stages of the disease
      process.

PMID- 24578125
TI  - Common variants in UMOD associate with urinary uromodulin levels: a meta
      analysis.
AB  - Uromodulin is expressed exclusively in the thick ascending limb and is the most
      abundant protein excreted in normal urine. Variants in UMOD, which encodes
      uromodulin, are associated with renal function, and urinary uromodulin levels may
      be a biomarker for kidney disease. However, the genetic factors regulating
      uromodulin excretion are unknown. We conducted a meta-analysis of urinary
      uromodulin levels to identify associated common genetic variants in the general
      population. We included 10,884 individuals of European descent from three genetic
      isolates and three urban cohorts. Each study measured uromodulin indexed to
      creatinine and conducted linear regression analysis of approximately 2.5 million
      single nucleotide polymorphisms using an additive model. We also tested whether
      variants in genes expressed in the thick ascending limb associate with uromodulin
      levels. rs12917707, located near UMOD and previously associated with renal
      function and CKD, had the strongest association with urinary uromodulin levels
      (P<0.001). In all cohorts, carriers of a G allele of this variant had higher
      uromodulin levels than noncarriers did (geometric means 10.24, 14.05, and 17.67
      MUg/g creatinine for zero, one, or two copies of the G allele). rs12446492 in the
      adjacent gene PDILT (protein disulfide isomerase-like, testis expressed) also
      reached genome-wide significance (P<0.001). Regarding genes expressed in the
      thick ascending limb, variants in KCNJ1, SORL1, and CAB39 associated with urinary
      uromodulin levels. These data indicate that common variants in the UMOD promoter
      region may influence urinary uromodulin levels. They also provide insights into
      uromodulin biology and the association of UMOD variants with renal function. 

PMID- 24578126
TI  - The cleaved cytoplasmic tail of polycystin-1 regulates Src-dependent STAT3
      activation.
AB  - Polycystin-1 (PC1) mutations result in proliferative renal cyst growth and
      progression to renal failure in autosomal dominant polycystic kidney disease
      (ADPKD). The transcription factor STAT3 (signal transducer and activator of
      transcription 3) was shown to be activated in cyst-lining cells in ADPKD and PKD
      mouse models and may drive renal cyst growth, but the mechanisms leading to
      persistent STAT3 activation are unknown. A proteolytic fragment of PC1
      corresponding to the cytoplasmic tail, PC1-p30, is overexpressed in ADPKD. Here,
      we show that PC1-p30 interacts with the nonreceptor tyrosine kinase Src,
      resulting in Src-dependent activation of STAT3 by tyrosine phosphorylation. The
      PC1-p30-mediated activation of Src/STAT3 was independent of JAK family kinases
      and insensitive to the STAT3 inhibitor suppressor of cytokine signaling 3.
      Signaling by the EGF receptor (EGFR) or cAMP amplified the activation of
      Src/STAT3 by PC1-p30. Expression of PC1-p30 changed the cellular response to cAMP
      signaling. In the absence of PC1-p30, cAMP dampened EGFR- or IL-6-dependent
      activation of STAT3; in the presence of PC1-p30, cAMP amplified Src-dependent
      activation of STAT3. In the polycystic kidney (PCK) rat model, activation of
      STAT3 in renal cystic cells depended on vasopressin receptor 2 (V2R) signaling,
      which increased cAMP levels. Genetic inhibition of vasopressin expression or
      treatment with a pharmacologic V2R inhibitor strongly suppressed STAT3 activation
      and reduced renal cyst growth. These results suggest that PC1, via its cleaved
      cytoplasmic tail, integrates signaling inputs from EGFR and cAMP, resulting in
      Src-dependent activation of STAT3 and a proliferative response. 

PMID- 24578127
TI  - MicroRNA-29a promotion of nephrin acetylation ameliorates hyperglycemia-induced
      podocyte dysfunction.
AB  - Podocyte dysfunction is a detrimental feature in diabetic nephropathy, with loss
      of nephrin integrity contributing to diabetic podocytopathy. MicroRNAs (miRs)
      reportedly modulate the hyperglycemia-induced perturbation of renal tissue
      homeostasis. This study investigated whether regulation of histone deacetylase
      (HDAC) actions and nephrin acetylation by miR-29 contributes to podocyte
      homeostasis and renal function in diabetic kidneys. Hyperglycemia accelerated
      podocyte injury and reduced nephrin, acetylated nephrin, and miR-29a levels in
      primary renal glomeruli from streptozotocin-induced diabetic mice. Diabetic miR
      29a transgenic mice had better nephrin levels, podocyte viability, and renal
      function and less glomerular fibrosis and inflammation reaction compared with
      diabetic wild-type mice. Overexpression of miR-29a attenuated the promotion of
      HDAC4 signaling, nephrin ubiquitination, and urinary nephrin excretion associated
      with diabetes and restored nephrin acetylation. Knockdown of miR-29a by antisense
      oligonucleotides promoted HDAC4 action, nephrin loss, podocyte apoptosis, and
      proteinuria in nondiabetic mice. In vitro, interruption of HDAC4 signaling
      alleviated the high glucose-induced apoptosis and inhibition of nephrin
      acetylation in podocyte cultures. Furthermore, HDAC4 interference increased the
      acetylation status of histone H3 at lysine 9 (H3K9Ac), the enrichment of H3K9Ac
      in miR-29a proximal promoter, and miR-29a transcription in high glucose-stressed
      podocytes. In conclusion, hyperglycemia impairs miR-29a signaling to intensify
      HDAC4 actions that contribute to podocyte protein deacetylation and degradation
      as well as renal dysfunction. HDAC4, via epigenetic H3K9 hypoacetylation, reduces
      miR-29a transcription. The renoprotective effects of miR-29a in diabetes-induced
      loss of podocyte integrity and renal homeostasis highlights the importance of
      post-translational acetylation reactions in podocyte microenvironments.
      Increasing miR-29a action may protect against diabetic podocytopathy. 

PMID- 24578128
TI  - Podocyte-specific VEGF-a gain of function induces nodular glomerulosclerosis in
      eNOS null mice.
AB  - VEGF-A and nitric oxide are essential for glomerular filtration barrier
      homeostasis and are dysregulated in diabetic nephropathy. Here, we examined the
      effect of excess podocyte VEGF-A on the renal phenotype of endothelial nitric
      oxide synthase (eNOS) knockout mice. Podocyte-specific VEGF(164) gain of function
      in eNOS(-/-) mice resulted in nodular glomerulosclerosis, mesangiolysis,
      microaneurysms, and arteriolar hyalinosis associated with massive proteinuria and
      renal failure in the absence of diabetic milieu or hypertension. In contrast,
      podocyte-specific VEGF(164) gain of function in wild-type mice resulted in less
      pronounced albuminuria and increased creatinine clearance. Transmission electron
      microscopy revealed glomerular basement membrane thickening and podocyte
      effacement in eNOS(-/-) mice with podocyte-specific VEGF(164) gain of function.
      Furthermore, glomerular nodules overexpressed collagen IV and laminin
      extensively. Biotin-switch and proximity ligation assays demonstrated that
      podocyte-specific VEGF(164) gain of function decreased glomerular S-nitrosylation
      of laminin in eNOS(-/-) mice. In addition, treatment with VEGF-A decreased S
      nitrosylated laminin in cultured podocytes. Collectively, these data indicate
      that excess glomerular VEGF-A and eNOS deficiency is necessary and sufficient to
      induce Kimmelstiel-Wilson-like nodular glomerulosclerosis in mice through a
      process that involves deposition of laminin and collagen IV and de-nitrosylation
      of laminin.

PMID- 24578129
TI  - Mechanism of salt-sensitive hypertension: focus on adrenal and sympathetic
      nervous systems.
AB  - A central role for the kidney among the systems contributing to BP regulation and
      the development of hypertension has been proposed. Both the
      aldosterone/mineralocorticoid receptor pathway and the renal sympathetic nervous
      system have important roles in the regulation of renal excretory function and BP
      control, but the mechanisms underlying these processes have remained unclear.
      However, recent studies revealed the activation of two pathways in salt-sensitive
      hypertension. Notably, Rac1, a member of the Rho-family of small GTP binding
      proteins, was identified as a novel ligand-independent modulator of
      mineralocorticoid receptor activity. Furthermore, these studies point to crucial
      roles for the Rac1-mineralocorticoid receptor-NCC/ENaC and the renal beta
      adrenergic stimulant-glucocorticoid receptor-WNK4-NCC pathways in certain rodent
      models of salt-sensitive hypertension. The nuclear mineralocorticoid and
      glucocorticoid receptors may contribute to impaired renal excretory function and
      the resulting salt-sensitive hypertension by increasing sodium reabsorption at
      different tubular segments. This review provides an in-depth discussion of the
      evidence supporting these conclusions and considers the significance with regard
      to treating salt-sensitive hypertension and salt-induced cardiorenal injury.

PMID- 24578131
TI  - Inhibition of periostin expression protects against the development of renal
      inflammation and fibrosis.
AB  - Increased renal expression of periostin, a protein normally involved in embryonic
      and dental development, correlates with the decline of renal function in
      experimental models and patient biopsies. Because periostin has been reported to
      induce cell differentiation, we investigated whether it is also involved in the
      development of renal disease and whether blocking its abnormal expression
      improves renal function and/or structure. After unilateral ureteral obstruction
      in wild-type mice, we observed a progressive increase in the expression and
      synthesis of periostin in the obstructed kidney that associated with the
      progression of renal lesions. In contrast, mice lacking the periostin gene showed
      less injury-induced interstitial fibrosis and inflammation and were protected
      against structural alterations. This protection was associated with a
      preservation of the renal epithelial phenotype. In vitro, administration of TGF
      beta to renal epithelial cells increased the expression of periostin several
      fold, leading to subsequent loss of the epithelial phenotype. Furthermore,
      treatment of these cells with periostin increased the expression of collagen I
      and stimulated the phosphorylation of FAK, p38, and ERK 42/44. In vivo delivery
      of antisense oligonucleotides to inhibit periostin expression protected animals
      from L-NAME-induced renal injury. These data strongly suggest that periostin
      mediates renal disease in response to TGF-beta and that blocking periostin may be
      a promising therapeutic strategy against the development of CKD. 

PMID- 24578130
TI  - Colony-stimulating factor-1 signaling suppresses renal crystal formation.
AB  - We recently reported evidence suggesting that migrating macrophages (Mphis)
      eliminate renal crystals in hyperoxaluric mice. Mphis can be inflammatory (M1) or
      anti-inflammatory (M2), and colony-stimulating factor-1 (CSF-1) mediates
      polarization to the M2Mphi phenotype. M2Mphis promote renal tissue repair and
      regeneration, but it is not clear whether these cells are involved in suppressing
      renal crystal formation. We investigated the role of M2Mphis in renal crystal
      formation during hyperoxaluria using CSF-1-deficient mice, which lack M2Mphis.
      Compared with wild-type mice, CSF-1-deficient mice had significantly higher
      amounts of renal calcium oxalate crystal deposition. Treatment with recombinant
      human CSF-1 increased the expression of M2-related genes and markedly decreased
      the number of renal crystals in both CSF-1-deficient and wild-type mice. Flow
      cytometry of sorted renal Mphis showed that CSF-1 deficiency resulted in a
      smaller population of CD11b(+)F4/80(+)CD163(+)CD206(hi) cells, which represent M2
      like Mphis. Additionally, transfusion of M2Mphis into CSF-1-deficient mice
      suppressed renal crystal deposition. In vitro phagocytosis assays with calcium
      oxalate monohydrate crystals showed a higher rate of crystal phagocytosis by M2
      polarized Mphis than M1-polarized Mphis or renal tubular cells. Gene array
      profiling showed that CSF-1 deficiency resulted in disordered M2- and stone
      related gene expressions. Collectively, our results provide compelling evidence
      for a suppressive role of CSF-1 signaling in renal crystal formation. 

PMID- 24578132
TI  - Shiga toxin promotes podocyte injury in experimental hemolytic uremic syndrome
      via activation of the alternative pathway of complement.
AB  - Shiga toxin (Stx)-producing Escherichia coli is the offending agent of
      postdiarrhea-associated hemolytic uremic syndrome (HUS), a disorder of glomerular
      ischemic damage and widespread microvascular thrombosis. We previously documented
      that Stx induces glomerular complement activation, generating C3a responsible for
      microvascular thrombosis in experimental HUS. Here, we show that the presence of
      C3 deposits on podocytes is associated with podocyte damage and loss in HUS mice
      generated by the coinjection of Stx2 and LPS. Because podocyte adhesion to the
      glomerular basement membrane is mediated by integrins, the relevance of integrin
      linked kinase (ILK) signals in podocyte dysfunction was evaluated. Podocyte
      expression of ILK increased after the injection of Stx2/LPS and preceded the
      upregulation of Snail and downregulation of nephrin and alpha-actinin-4. Factor B
      deficiency or pretreatment with an inhibitory antibody to factor B protected mice
      against Stx2/LPS-induced podocyte dysregulation. Similarly, pretreatment with a
      C3a receptor antagonist limited podocyte loss and changes in ILK, Snail, and
      alpha-actinin-4 expression. In cultured podocytes, treatment with C3a reduced
      alpha-actinin-4 expression and promoted ILK-dependent nuclear expression of Snail
      and cell motility. These results suggest that Stx-induced activation of the
      alternative pathway of complement and generation of C3a promotes ILK signaling,
      leading to podocyte dysfunction and loss in Stx-HUS. 

PMID- 24578133
TI  - The basic domain of HIV-tat transactivating protein is essential for its
      targeting to lipid rafts and regulating fibroblast growth factor-2 signaling in
      podocytes isolated from children with HIV-1-associated nephropathy.
AB  - Podocyte injury has a critical role in the pathogenesis of HIV-associated
      nephropathy (HIVAN). The HIV-1 transactivator of transcription (Tat), combined
      with fibroblast growth factor-2 (FGF-2), can induce the dedifferentiation and
      proliferation of cultured human podocytes. Cellular internalization of Tat
      requires interactions with heparan sulfate proteoglycans and cholesterol-enriched
      lipid rafts (LRs). However, the specific distribution of Tat in human podocytes
      and its ability to associate with LRs have not been documented. Here, we found
      that Tat is preferentially recruited to LRs in podocytes isolated from children
      with HIVAN. Furthermore, we identified arginines in the basic domain (RKKRRQRRR)
      of Tat as essential for (1) targeting Tat to LRs, (2) Tat-mediated increases in
      the expression of Rho-A and matrix metalloproteinase-9 in LRs, and (3) Tat
      mediated enhancement of FGF-2 signaling in human podocytes and HIV-transgenic
      mouse kidneys and the exacerbation of renal lesions in these mice. Tat carrying
      alanine substitutions in the basic domain (AKKAAQAAA) remained localized in the
      cytosol and did not associate with LRs or enhance FGF-2 signaling in cultured
      podocytes. These results show the specific association of Tat with LRs in
      podocytes isolated from children with HIVAN, confirm Tat as a regulator of FGF-2
      signaling in LRs, and identify the key domain of Tat responsible for promoting
      these effects and aggravating renal injury in HIV-transgenic mice. Moreover,
      these results provide a molecular framework for developing novel therapies to
      improve the clinical outcome of children with HIVAN. 

PMID- 24578136
TI  - Journey to the summits of science: the 2014 Vilcek Foundation prizes.

PMID- 24578134
TI  - Sphingosine-1-phosphate evokes unique segment-specific vasoconstriction of the
      renal microvasculature.
AB  - Sphingosine-1-phosphate (S1P), a bioactive sphingolipid metabolite, has been
      implicated in regulating vascular tone and participating in chronic and acute
      kidney injury. However, little is known about the role of S1P in the renal
      microcirculation. Here, we directly assessed the vasoresponsiveness of
      preglomerular and postglomerular microvascular segments to exogenous S1P using
      the in vitro blood-perfused juxtamedullary nephron preparation. Superfusion of
      S1P (0.001-10 MUM) evoked concentration-dependent vasoconstriction in
      preglomerular microvessels, predominantly afferent arterioles. After
      administration of 10 MUM S1P, the diameter of afferent arterioles decreased to
      35%+/-5% of the control diameter, whereas the diameters of interlobular and
      arcuate arteries declined to 50%+/-12% and 68%+/-6% of the control diameter,
      respectively. Notably, efferent arterioles did not respond to S1P. The S1P
      receptor agonists FTY720 and FTY720-phosphate and the specific S1P1 receptor
      agonist SEW2871 each evoked modest afferent arteriolar vasoconstriction.
      Conversely, S1P2 receptor inhibition with JTE-013 significantly attenuated S1P
      mediated afferent arteriolar vasoconstriction. Moreover, blockade of L-type
      voltage-dependent calcium channels with diltiazem or nifedipine attenuated S1P
      mediated vasoconstriction. Intravenous injection of S1P in anesthetized rats
      reduced renal blood flow dose dependently. Western blotting and
      immunofluorescence revealed S1P1 and S1P2 receptor expression in isolated
      preglomerular microvessels and microvascular smooth muscle cells. These data
      demonstrate that S1P evokes segmentally distinct preglomerular vasoconstriction
      via activation of S1P1 and/or S1P2 receptors, partially via L-type voltage
      dependent calcium channels. Accordingly, S1P may have a novel function in
      regulating afferent arteriolar resistance under physiologic conditions. 

PMID- 24578137
TI  - Retraction.

PMID- 24578138
TI  - The path of the superior sagittal sinus in unicoronal synostosis.
AB  - PURPOSE: This study investigates the anatomic relationship between the superior
      sagittal sinus (SSS) and the sagittal suture in infants with uncorrected
      unicoronal synostosis. The morphology of the SSS is also evaluated
      postoperatively to assess whether normalization of intracranial structures occurs
      following reconstruction. METHODS: The study sample consisted of 20 computed
      tomography scans (10 preoperative, 6 postoperative, and 4 unaffected controls)
      obtained between 2001 and 2013. The SSS and the sagittal suture were outlined
      using Analyze imaging software. These data were used to measure the maximum
      lateral discrepancy between the SSS and the sagittal suture preoperatively and to
      assess for postoperative changes in the morphology of the SSS. RESULTS: In
      children with uncorrected unicoronal synostosis, the SSS deviates to the side of
      the patent coronal suture posteriorly and tends to follow the path of the
      sagittal and metopic sutures. The lateral discrepancy between the SSS and the
      sagittal suture ranged from 5.0 to 11.8 mm, with a 99.9 % upper prediction bound
      of 14.4 mm. Postoperatively, the curvature of the SSS was statistically decreased
      following surgical intervention, though it remained significantly greater than in
      unaffected controls. CONCLUSIONS: The SSS follows a predictable course relative
      to surface landmarks in children with unicoronal synostosis. When creating burr
      holes for craniotomies, the SSS can be avoided in 99.9 % of cases by remaining at
      least 14.4 mm from the lateral edge of the sagittal suture. Postoperative changes
      in the path of the SSS provide indirect evidence for normalization of regional
      brain morphology following fronto-orbital advancement.

PMID- 24578135
TI  - CKD-induced wingless/integration1 inhibitors and phosphorus cause the CKD-mineral
      and bone disorder.
AB  - In chronic kidney disease, vascular calcification, renal osteodystrophy, and
      phosphate contribute substantially to cardiovascular risk and are components of
      CKD-mineral and bone disorder (CKD-MBD). The cause of this syndrome is unknown.
      Additionally, no therapy addresses cardiovascular risk in CKD. In its inception,
      CKD-MBD is characterized by osteodystrophy, vascular calcification, and
      stimulation of osteocyte secretion. We tested the hypothesis that increased
      production of circulating factors by diseased kidneys causes the CKD-MBD in
      diabetic mice subjected to renal injury to induce stage 2 CKD (CKD-2 mice).
      Compared with non-CKD diabetic controls, CKD-2 mice showed increased renal
      production of Wnt inhibitor family members and higher levels of circulating
      Dickkopf-1 (Dkk1), sclerostin, and secreted klotho. Neutralization of Dkk1 in CKD
      2 mice by administration of a monoclonal antibody after renal injury stimulated
      bone formation rates, corrected the osteodystrophy, and prevented CKD-stimulated
      vascular calcification. Mechanistically, neutralization of Dkk1 suppressed aortic
      expression of the osteoblastic transcription factor Runx2, increased expression
      of vascular smooth muscle protein 22-alpha, and restored aortic expression of
      klotho. Neutralization of Dkk1 did not affect the elevated plasma levels of
      osteocytic fibroblast growth factor 23 but decreased the elevated levels of
      sclerostin. Phosphate binder therapy restored plasma fibroblast growth factor 23
      levels but had no effect on vascular calcification or osteodystrophy. The
      combination of the Dkk1 antibody and phosphate binder therapy completely treated
      the CKD-MBD. These results show that circulating Wnt inhibitors are involved in
      the pathogenesis of CKD-MBD and that the combination of Dkk1 neutralization and
      phosphate binding may have therapeutic potential for this disorder. 

PMID- 24578140
TI  - Intervention effects of knowledge and skills of the public to respond to public
      health emergencies in Sichuan province, China.
AB  - BACKGROUND: Public health emergencies have a significant impact on the health of
      citizens, the local economy, and society as a whole. Currently, in many parts of
      China, there is a widespread lack of the knowledge and skills required for
      emergency preparedness and self-rescue. By carrying out targeted health education
      and intervention activities, and by popularizing the knowledge and skills in
      health emergencies, the abilities of citizens to respond to public health
      emergencies and protect themselves, reduce property damage, and eliminate
      unnecessary panic may be greatly improved. OBJECTIVES: The knowledge and skills
      of the public to respond to public health emergencies after an intervention in
      Sichuan province were surveyed. The conditions before and after the intervention
      were compared, and the effect of the intervention was evaluated. METHODS: Four
      counties in Sichuan province were selected for baseline survey by means of a
      multistage random sampling method. Among the districts and counties, one of each
      was selected for baseline survey as an intervention group and another of each
      were selected as controls. After 1 year of intervention, respondents were
      selected from the intervention group by means of the method used for the baseline
      survey for effect evaluation. RESULTS: After statistical analysis, it was shown
      that, after the intervention, the total awareness rate of knowledge to respond to
      public health emergencies increased from 42.6% to 58.4% among men and from 42.9%
      to 55.8% among women, both significant differences (p < .001). It was also shown
      that the total awareness rates of the 18-35, 36-45, 46-60, and 60+ age-groups,
      respectively, increased from 44.5%, 43.7%, 42.2%, and 37.8% to 62.1%, 56.0%,
      56.8%, and 51.9%, which were also significant differences (p < .001).
      Intervention, educational level, occupation, discussion with the families, and
      disaster experience were the main influential factors for the knowledge and
      skills of sudden public health events. CONCLUSIONS: The study results show that,
      after the intervention in Sichuan province, the knowledge and skills of the
      public to respond to public health emergencies were significantly improved. It is
      also shown that health education interventions must be developed in accordance
      with geographical features, the educational level of the population, age
      characteristics, and other factors.

PMID- 24578139
TI  - Normal pressure hydrocephalus as a failure of ICP homeostasis mechanism: the
      hidden role of Monro-Kellie doctrine in the genesis of NPH.
AB  - OBJECTIVE: The theme of this paper is to outline that the genesis of normal
      pressure hydrocephalus (NPH) is governed by the intracranial pressure (ICP)
      homeostatic principle. The development of this new concept is based mainly on
      rethinking the well-known Monro-Kellie doctrine in the way that ICP homeostasis
      mechanism is not only a mechanism that works to prevent pathologically high ICP
      but also a mechanism that aims to protect from pathologically low ICP. METHODS:
      The NPH-related literatures are reviewed and reinterpreted to generate a new
      paradigm for the cascade of pathophysiological events that leads to the genesis
      NPH, as well as the mechanism of clinical beneficial effects and complications of
      the shunting procedure. RESULTS: According to this new paradigm, the suboptimal
      cerebral perfusion that is associated with the impairment of the cerebral
      autoregulation is the initial step in the genesis of NPH. When the overall volume
      of blood that circulates intracranially is diminished, a chronic low ICP with
      episodes of pathologically low ICP occurs. Since the cranial vault is not
      collapsible, those episodes of low ICP are compensated by the accumulation of
      cerebrospinal fluid (CSF) to keep the ICP in normal ideal range. The impairment
      of brain toxin-flushing mechanism because of CSF pooling combined with the
      already-established suboptimal cerebral perfusion leads to functional
      disinhibition of the cerebral cortex. CONCLUSION: Recognizing the importance of
      ICP homeostatic mechanisms in the genesis of the NPH is a simple yet novel view
      that could change the way we look at NP and can give a basic and fundamental
      theoretical frame work to achieve better understanding of NPH.

PMID- 24578141
TI  - Editors' introduction: advancing program evaluation methods in criminology and
      criminal justice.

PMID- 24578147
TI  - Design of a continuous process setup for precipitated calcium carbonate
      production from steel converter slag.
AB  - A mineral carbonation process "slag2PCC" for carbon capture, utilization, and
      storage is discussed. Ca is extracted from steel slag by an ammonium salt solvent
      and carbonated with gaseous CO2 after the separation of the residual slag. The
      solvent is reused after regeneration. The effects of slag properties such as the
      content of free lime, fractions of Ca, Si, Fe, and V, particle size, and slag
      storage on the Ca extraction efficiency are studied. Small particles with a high
      free-lime content and minor fractions of Si and V are the most suitable. To limit
      the amount of impurities in the process, the slag-to-liquid ratio should remain
      below a certain value, which depends on the slag composition. Also, the design of
      a continuous test setup (total volume ~75 L) is described, which enables quick
      process variations needed to adapt the system to the varying slag quality.
      Different precipitated calcium carbonate crystals (calcite and vaterite) are
      generated in different parts of the setup. 

PMID- 24578142
TI  - Incident heart failure in relation to vascular disease: insights from the Health,
      Aging, and Body Composition Study.
AB  - AIMS: The contribution of heart failure (HF) unrelated to vascular disease to the
      overall HF burden in older adults is not well characterized. This was
      investigated in this study. METHODS AND RESULTS: We assessed HF incidence and
      outcomes in 2895 participants of the Health ABC Study (age 74 +/- 3 years, 48.4%
      men, 41.4% black) in relation to vascular disease (coronary, peripheral, or
      cerebrovascular disease) either present at baseline or developed prior to HF.
      During 11.4 years follow-up, 493 participants developed HF; 134 (27.2%) in
      participants without any prior vascular disease and 177 (36.8%) without coronary
      disease. Both baseline [hazard ratio (HR) 2.4, 95% confidence interval (CI) 1.9
      2.8] and incident vascular disease (HR 4.3, 95% CI 3.6-5.2) were associated with
      HF. During a median follow-up of 2.1 years after HF onset, 67.5% participants
      died. Annual mortality after HF development was 21.3% in those with compared with
      24.6% in those without vascular disease (HR 1.11, 95% CI 0.87-1.43; P = 0.399).
      There were 658 all-cause (436.3/1000 person-years) and 523 HF-related (346.4/1000
      person-years) hospitalizations after HF development. There was no significant
      difference in hospitalizations between those with and without vascular disease
      [rate ratio (RR) 1.04, 95% CI 0.86-1.24 for all-cause, and RR 0.84 95% CI 0.69
      1.02 for HF hospitalization]. HF with preserved EF was more common in
      participants without vascular disease (67.0% vs. 55.0%, P = 0.040). CONCLUSION: A
      significant proportion of HF in older adults develops without prior vascular
      disease. Outcomes for these patients are poor compared with those with preceding
      vascular disease. These data suggest the need for more targeted HF prediction and
      prevention efforts.

PMID- 24578148
TI  - Measurement properties of the Client-centered Care Questionnaire (CCCQ): factor
      structure, reliability and validity of a questionnaire to assess self-reported
      client-centeredness of home care services in a population of frail, older people.
AB  - BACKGROUND: The increasing and specific use of home care services by frail, older
      people asks for the evaluation of the client-centeredness of these services. To
      our knowledge, no instrument that measures client-centeredness of home care from
      this group's unique perspective exists. We therefore tested the factor structure,
      reliability, content validity and acceptability of the Client-centered Care
      Questionnaire (CCCQ), an existing instrument developed for general home care
      users, in a population of frail, older people in the Netherlands. METHODS: We
      used data from a 2-year clinical trial. STUDY POPULATION: frail, older people who
      received home care. Data were collected at baseline (n = 600) and 24-month
      measurements (n = 389); retest data (n = 67) were collected 7-14 days after the
      24-month measurements. ANALYSES: We performed confirmatory factor analysis,
      investigated reliability and validity parameters and assessed acceptability.
      RESULTS: The factor analysis yielded a bifactor model with essential
      unidimensionality. Internal consistency was high (omega total .88). We found a
      test-retest reliability of total test scores of .81; the standard error of
      measurement was 2.61 (total score range 15-75) and the limits of agreement were 
      7.03 and 7.86. We rejected three out of four hypotheses for construct validity.
      CONCLUSIONS: The CCCQ is sufficiently unidimensional to permit the use of total
      test scores. We found acceptable reliability values, but considered our results
      on construct validity inconclusive. Respondents found the CCCQ questions
      challenging to answer, which is indicative of a high degree of respondent burden.
      Future instruments that measure client-centeredness of home care from the frail,
      older client's perspective should therefore be tailored to the specific
      circumstances of this population.

PMID- 24578150
TI  - Psychosocial determinants of quality of life in parents of obese children seeking
      inpatient treatment.
AB  - PURPOSE: To examine and identify predictors of parental health-related quality of
      life (HRQoL) in a sample of obese and very obese children participating in an
      inpatient program for treating obesity. METHODS: Data are part of a prospective
      multicenter randomized-controlled intervention trial. Parents (n = 463) of obese
      and very obese children (7-13 years) completed standardized questionnaires
      assessing their own and their child's HRQoL, psychosocial functioning,
      demographics and parental weight-specific self-efficacy on the child's admission
      to an inpatient pediatric weight management program. Weight and height of the
      children were measured by trained personnel; parental weight was assessed via
      self-report. RESULTS: Parents reported lower mental HRQoL compared to healthy
      adults and even lower than reference values for acute or chronic illness. With
      respect to physical HRQoL, parents of obese children reported higher scores than
      both groups. Effect sizes were small to medium. Overweight parents reported a
      lower physical HRQoL. Mental HRQoL was higher for married parents with a higher
      educational level and a higher self-efficacy and for those whose children
      depicted fewer behavioral problems and reported a higher HRQoL. Hierarchical
      regression analyses revealed that weight-specific self-efficacy explained 3% of
      variance in mental HRQoL in addition to the demographic and child psychosocial
      variables. Parental self-efficacy also partially mediated the association between
      the child's HRQoL and parental mental HRQoL. CONCLUSION: Childhood obesity is
      associated with reduced parental HRQoL. Interventions for obesity in children
      should consider the parents' psychosocial situation as well. Enhancing parental
      self-efficacy may be a promising approach.

PMID- 24578149
TI  - "We both just trusted and leaned on the Lord": a qualitative study of
      religiousness and spirituality among African American breast cancer survivors and
      their caregivers.
AB  - PURPOSE: Most breast cancer (BC) survivorship research focuses on the general
      population of survivors. Scant research investigates the potentially unique
      experiences of minorities, especially during and after the difficult transition
      from primary treatment to post-treatment. This qualitative study explored African
      American BC survivors' and caregivers' quality-of-life in the post-treatment
      period with a focus on social and spiritual well-being. METHODS: Participants
      included a convenience sample of African American women with stage I-III BC (N =
      23) who completed treatment 6-24 months before enrollment. Primary caregivers (N
      = 22) included friends, spouses and other family members (21 complete dyads).
      Participants completed separate semi-structured telephone interviews. Template
      analysis was used to evaluate themes related to religiousness and spirituality,
      both across and within dyads. RESULTS: After treatment, religiousness and
      spirituality played a major role in both survivors' and caregivers' lives by: (1)
      providing global guidance, (2) guiding illness management efforts and (3)
      facilitating recovery. Participants described a spiritual connectedness with God
      and others in their social networks. Dyad members shared the goal of keeping a
      positive attitude and described positive growth from cancer. Few future concerns
      were expressed due to the belief that survivors were healed and "done" with
      cancer. Beyond practical and emotional support, provision of spiritual assistance
      was common. CONCLUSIONS: Results highlight the principal, positive role of
      religiousness and spirituality for African American BC survivors and caregivers
      after treatment. Findings emphasize the need to assess the importance of
      religious and spiritual beliefs and practices, and if appropriate, to provide
      resources that promote spiritual well-being.

PMID- 24578151
TI  - Duration of diabetes and effectiveness of insulin in the management of insulin
      naive Korean patients uncontrolled on oral antidiabetic drugs: a sub-analysis of
      the MOdaliTy of Insulin treatment eValuation (MOTIV) registry results.
AB  - To investigate whether duration of diabetes has an impact on the effectiveness of
      insulinization in diabetes management. This open-label, noninterventional,
      observational registry was conducted at >500 centers in Korea. Patients with
      diabetes, on oral antidiabetic drugs, with HbA1c >=7 % (53 mmol/mol) in the
      preceding 3 months, being considered for initiation of basal insulin by their
      physicians, were included. Data were collected at baseline and at 3 and 6 months.
      Of 6,616 patients evaluated, 62.5 % had diabetes for <10 years, while only 6.5 %
      patients had diabetes for >=20 years. At the end of study, average HbA1c in
      patients with diabetes for <10 years, for 10 to <20 years, and for >=20 years was
      7.3 +/- 1.0 % (56 +/- 10.9 mmol/mol), 7.4 +/- 1.0 % (57 +/- 10.9 mmol/mol), and
      7.6 +/- 1.1 % (60 +/- 12.0 mmol/mol), respectively. Over half the patients (50.7
      %) with diabetes <10 years achieved HbA1c <7 % (53 mmol/mol) by the end of study,
      while only 42.1 and 35.1 % patients with diabetes for 10 to <20 and >=20 years,
      respectively, achieved their target. The average insulin dosage required for per
      unit HbA1c reduction was significantly different among the groups according to
      duration of type 2 diabetes mellitus (p < 0.05). Among patients who achieved
      HbA1c <7 %, proportion of patients with hypoglycemia in the >=20 years group was
      higher than that in the <10 years, 10 to <20 years groups. Early insulin
      administration provided a better glycemic control with less insulin dosage and
      lower frequency of hypoglycemic events. Thus, early insulinization might hold the
      key to better management of type 2 diabetes mellitus. 

PMID- 24578152
TI  - Subjective age-of-acquisition norms for 7,039 Spanish words.
AB  - Subjective estimations of age of acquisition (AoA) for a large pool of Spanish
      words were collected from college students in Spain. The average score for each
      word (based on 50 individual responses, on a scale from 1 to 11) was taken as an
      AoA indicator, and normative values for a total of 7,039 single words are
      provided as supplemental materials. Beyond its intrinsic value as a standalone
      corpus, the largest of its kind for Spanish, the value of the database is
      enhanced by the fact that it contains most of the words that are currently
      included in other normative studies, allowing for a more complete
      characterization of the lexical stimuli that are usually employed in studies with
      Spanish-speaking participants. The norms are available for downloading as
      supplemental materials with this article. 

PMID- 24578153
TI  - Cytosolic expression of synthetic phytochelatin and bacterial metallothionein
      genes in Deinococcus radiodurans R1 for enhanced tolerance and bioaccumulation of
      cadmium.
AB  - Due to its exemplary resistance to ionising radiation, oxidative stress,
      desiccation and several DNA damaging agents, Deinococcus radiodurans R1 (DR1) is
      considered as one of the most appropriate candidates for the bioremediation of
      the nuclear waste sites. However, the high sensitivity of this bacterium to heavy
      metals, which are usually preponderant at nuclear waste dump sites, precludes its
      application for bioremediation. This study deals with the expression two metal
      binding peptides in DR1 as an attractive strategy for developing metal tolerance
      in this bacterium. A synthetic gene (EC20) encoding a phytochelatin analogue with
      twenty repeating units of glutamate and cysteine was constructed by overlap
      extension and expressed in DR1. The cyanobacterial metallothionein (MT) gene,
      smtA was cloned for intracellular expression in DR1. Both the genes were
      expressed under the native groESL promoter. DR1 strain carrying the recombinant
      EC20 demonstrated 2.5-fold higher tolerance to Cd(2+) and accumulated 1.21-fold
      greater Cd(2+) as opposed to the control while the heterologous expression of MT
      SmtA in DR1 imparted the transformant superior tolerance to Cd(2+) amassing 2.5
      fold greater Cd(2+) than DR1 expressing EC20. 

PMID- 24578155
TI  - The relationship between the intercostal distance, patient height and outcome in
      microsurgical breast reconstruction using the second interspace rib-sparing
      internal mammary vessel exposure.
AB  - PURPOSE OF THE STUDY: Rib-sparing internal mammary vessel (IMV) exposure in
      breast reconstruction is becoming common, with a smaller space in which to
      perform the microanastomoses. The objectives were to determine whether patient
      height could be used as a proxy measurement for intercostal distance (ICD),
      assess whether the complication rate or the flap ischemia time are affected in
      such surgery, and provide anatomical data about ICDs. METHODS: Data were
      collected from 95 consecutive patients (109 breasts) undergoing free flap breast
      reconstruction using rib-sparing vessel exposure over a 3-year period by one
      surgeon. Pearson's product moment correlation coefficient was used to assess the
      relation between height and ICD, body mass index (BMI), operative times, and flap
      outcomes. RESULTS: There was no correlation between patient height and ICD (r =
      0.087), age, BMI, recipient vessel preparation time, and flap ischemia time.
      CONCLUSION: Being able to predict patients with a small ICD in whom microsurgery
      may be more challenging can influence surgical planning. The anatomy of the
      intercostal spaces is variable and was not predictable in relation to height,
      BMI, or age. Height was not a reliable proxy for ICD and where there is a concern
      about the available ICD it is suggested that it is measured directly through
      preoperative imaging. This study found no increase in the complication rate and
      flap ischemia time using the rib-sparing IMV exposure technique.

PMID- 24578154
TI  - It's who you know: patient-sharing, quality, and costs of cancer survivorship
      care.
AB  - PURPOSE: Cancer survivors frequently receive care from a large number of
      physicians, creating challenges for coordination. We sought to explore whether
      cancer survivors whose providers have more patients in common (e.g., shared
      patients) tend to have higher quality and lower cost care. METHODS: We performed
      a retrospective cohort study of 8,661 patients diagnosed with loco-regional
      breast, prostate, or colorectal cancer. We examined survivorship care from days
      366 to 1,095 following their cancer diagnosis. Our primary independent variable
      was "care density," a novel metric of the extent to which a patient's providers
      share patients with one another. Our outcome measures were health care
      utilization, quality metrics, and costs. RESULTS: In adjusted analyses, we found
      that patients with high care density--indicating high levels of patient-sharing
      among their providers--had significantly lower rates of hospitalization (OR 0.87,
      95% CI 0.75-1.00) and higher odds of an eye examination for diabetes (OR 1.31,
      95% CI 1.03-1.66) compared to patients with low care density. High care density
      was not associated with emergency department visits, avoidable outcomes, lipid
      profile following an angina diagnosis, or odds of glycosylated hemoglobin testing
      for diabetes. Patients with high care density had significantly lower total costs
      of care over 24 months (beta coefficient -$2,116, 95% CI -$3,107 to -$1,125)
      along with lower inpatient and outpatient costs. CONCLUSION: Cancer survivors
      treated by physicians who share more patients with one another tend to have some
      higher aspects of quality and lower cost care. IMPLICATIONS OF CANCER SURVIVORS:
      If validated, care density may be a useful indicator for monitoring care
      coordination among cancer survivors and potentially targeting interventions that
      seek to improve care delivery.

PMID- 24578156
TI  - Factors Affecting Hispanic Women's Participation in Screening for Cervical
      Cancer.
AB  - Hispanic women's cervical cancer rates are disproportionately high. The Health
      Belief Model (HBM) was used as a theoretical framework to explore beliefs,
      attitudes, socio-economic, and cultural factors influencing Hispanic women's
      decisions about cervical cancer screening. A cross-sectional survey was conducted
      among Hispanic women 18-65 years old (n = 205) in the Upstate of South Carolina.
      Generalized Linear Modeling was used. Across all models, perceived threats
      (susceptibility and severity), self-efficacy, and the interaction of benefits and
      barriers were significant predictors. Significant covariates included age,
      marital status, income, regular medical care, and familism. A modified HBM was a
      useful model for examining cervical cancer screening in this sample of Hispanic
      women. The inclusion of external, or social factors increased the strength of the
      HBM as an explanatory model. The HBM can be used as a framework to design
      culturally appropriate cervical cancer screening interventions.

PMID- 24578157
TI  - Subclinical cognitive decline in middle-age is associated with reduced task
      induced deactivation of the brain's default mode network.
AB  - Cognitive abilities decline with age, but with considerable individual variation.
      The neurobiological correlate of this variation is not well described. Functional
      brain imaging studies have demonstrated reduced task-induced deactivation (TID)
      of the brain's default mode network (DMN) in a wide range of neurodegenerative
      diseases involving cognitive symptoms, in conditions with increased risk of
      Alzheimer's disease, and even in advanced but healthy aging. Here, we
      investigated brain activation and deactivation during a visual-motor task in 185
      clinically healthy males from a Danish birth cohort, whose cognitive function was
      assessed in youth and midlife. Using each individual as his own control, we
      defined a group with a large degree of cognitive decline, and a control group.
      When correcting for effects of total cerebral blood flow and hemoglobin level, we
      found reduced TID in the posterior region of the DMN in the cognitive decline
      group compared to the control group. Furthermore, increased visual activation
      response was found in the cognitive decline group, indicating that the TID
      reduction was not exclusively due to overall impaired vascular reactivity. These
      results suggest a neurobiological basis for subclinical cognitive decline in late
      midlife, which includes TID alterations similar to the pattern seen in patients
      with AD and mild cognitive impairment. Hence, TID reduction might be suggested as
      an early marker for subtle cognitive decline in aging.

PMID- 24578158
TI  - Association of novel gene polymorphisms RRM1 -756T>C and -269 C>A with breast
      cancer.
AB  - BACKGROUND: Genetic variants are reported to play an important role in the
      susceptibility of breast cancer. Ribonucleotide reductase 1 (RRM1) is suggested
      to play an essential role in the regulation of cancer development. The purpose of
      this study was to identify novel gene polymorphisms of RRM1 -756T>C and RRM1 -269
      C>A specific to patients with breast cancer and healthy controls. METHODS: A
      total of 833 subjects, including 321 healthy controls and 512 patients with
      breast cancer, were recruited in this study. Allelic discrimination of RRM1 
      756T>C (rs11030919) and RRM1 -269C>A (rs12806698) polymorphisms of the RRM1 gene
      was assessed with the real-time polymerase chain reaction. RESULTS: The adjusted
      odds ratios and 95% confidence intervals were 1.20 (0.71-2.04) and 1.10 (0.65
      1.86) to have breast cancer among individuals with CC alleles of RRM1 -756T>C and
      individuals with AA alleles of RRM1 -269C>A gene polymorphism, respectively,
      compared to individuals having wild type of RRM1 gene polymorphisms. Also, there
      was no significant genetic interaction effect on the susceptibility of breast
      cancer and nonassociation between genetic polymorphisms and clinical statuses of
      breast cancer. CONCLUSION: Gene polymorphisms of RRM1 -756T>C and RRM1 -269C>A
      may be not an important factor for the susceptibility of breast cancer.

PMID- 24578160
TI  - MiR-29a/b/c regulate human circadian gene hPER1 expression by targeting its
      3'UTR.
AB  - Several essential biological progresses in mammals are regulated by circadian
      rhythms. Though the molecular mechanisms of oscillating these circadian rhythms
      have been uncovered, the specific functions of the circadian genes are not very
      clear. It has been reported that knocking down circadian genes by microRNA is a
      useful strategy to explore the function of the circadian rhythms. In this study,
      through a forward bioinformatics screening approach, we identified miR-29a/b/c as
      potent inhibitors for the human circadian gene hPER1. We further found that miR
      29a/b/c could directly target hPER1 3'untranslated region (UTR) and down-regulate
      hPER1 at both mRNA and protein expression levels in human A549 cells. Thus, our
      findings suggested that the expression of hPER1 is regulated by miR-29a/b/c,
      which may also provide a new clue for the function of hPER1. 

PMID- 24578159
TI  - Carboxyl terminus of Hsp70-interacting protein regulation of osteoclast formation
      in mice through promotion of tumor necrosis factor receptor-associated factor 6
      protein degradation.
AB  - OBJECTIVE: Carboxyl terminus of Hsp70-interacting protein (CHIP or STUB1) is an
      E3 ligase that regulates the stability of several proteins involved in tumor
      growth and metastasis. However, the role of CHIP in bone growth and bone
      remodeling in vivo has not been reported. This study was undertaken to
      investigate the role and mechanism of CHIP in regulation of bone mass and bone
      remodeling. METHODS: The bone phenotype of Chip(-/-) mice was assessed by
      histologic, histomorphometric, and micro-computed tomographic analyses. The
      mechanism by which CHIP regulates the degradation of tumor necrosis factor
      receptor-associated factor 6 (TRAF6) and the inhibition of NF-kappaB signaling
      was examined by immunoprecipitation, Western blot, and luciferase reporter
      assays. RESULTS: Deletion of the Chip gene led to an osteopenic phenotype and
      increased osteoclast formation. TRAF6, an adaptor protein that is a key regulator
      of NF-kappaB signaling and is critical for RANKL-induced osteoclastogenesis, was
      up-regulated in osteoclasts from Chip(-/-) mice. CHIP interacted with TRAF6 to
      promote TRAF6 ubiquitination and proteasome degradation. Further, CHIP inhibited
      p65 nuclear translocation, leading to the repression of TRAF6-mediated NF-kappaB
      transcription. CONCLUSION: CHIP inhibits NF-kappaB signaling by promoting TRAF6
      degradation and plays an important role in osteoclastogenesis and bone
      remodeling. These findings suggest that CHIP may be a novel therapeutic target in
      bone loss-associated disorders.

PMID- 24578161
TI  - Variations of thioredoxin system contributes to increased susceptibility to
      apoptosis in cardiomyocytes of type 2 diabetic rats.
AB  - Cardiac complications are the leading cause of death in diabetes. However, the
      mechanism of diabetes in inducing myocardial injury and apoptosis, and whether
      the thioredoxin (Trx) system is involved remain unclear. In this study, male
      Sprague-Dawley rats were randomly divided into two groups: the control and the
      diabetes groups, and then were randomly divided into five different timepoints
      (the 1st, 2nd, 4th, 12th, and 24th week). The results showed that diabetes
      induced cardiac injury was enhanced in the type 2 diabetes rats, as evidenced by
      aggravated cardiac dysfunction, biochemical indicators, and increased myocardial
      apoptosis (TUNEL and caspase-3 activity). The activity of myocardial Trx and Trx
      reductase (TR) in diabetic rats was significantly decreased from the second week
      and continually aggravated with the disease progression. In diabetic rats, the
      mRNA expression of Trx1, Trx2, TR1, and TR2 was decreased first and then
      increased after the fourth week. Meanwhile, the protein expression of these Trx
      system members was significantly increased at the 12th week. Trx nitration was
      cleared, the Trx/ASK1 interaction was significantly decreased, and the activity
      of p38 was significantly enhanced in cardiac tissues at the 12th week. These
      results demonstrated that diabetes may cause myocardial injury and apoptosis, and
      the extent of which was accompanied with the development of the disease. The
      mechanism is associated with the development of diabetes and the decreased
      activity of Trx and TR. The reasons for decreased Trx activity may include:
      decrease of Trx and TR protein expression; nitration modification of Trx; and up
      regulation of TXNIP expression. 

PMID- 24578162
TI  - Local feature suppression effect in face and non-face stimuli.
AB  - There is evidence that the cognitive system processes human faces faster and more
      precisely than other stimuli. Also, faces summon visual attention in an automatic
      manner, as evidenced by efficient, 'pop-out' search for face targets amongst
      homogeneous non-face distractors. Pop-out for faces implies that faces are
      processed as a basic visual 'feature' by specialized face-tuned detectors,
      similar to the coding of other features (e.g., color, orientation, motion, etc.).
      However, it is unclear whether such face detectors encode only the global face
      configuration or both global and local face features. If the former were correct,
      the face detectors should be unable to support search for a local face feature,
      rendering search slower relative to non-face stimuli; that is, there would be
      local feature suppression (LFS) for faces. If the latter was the case, there
      should be no difference in the processing of local and, respectively, global face
      features. In two experiments, participants discerned the presence (vs. absence)
      of a local target defined as a part of either a normal or a scrambled (schematic
      or realistic) face or of a non-face (Kanizsa diamond or realistic house)
      configuration. The results consistently showed a robust LFS effect in both
      reaction times and error rates for face stimuli, and either no difference or even
      a local feature enhancement effect for the control stimuli. Taken together, these
      findings indicate that faces are encoded as a basic visual feature by means of
      globally tuned face detectors. 

PMID- 24578163
TI  - Pediatric child abuse victim with posttraumatic inferior vena cava thrombosis.
AB  - Posttraumatic inferior vena cava thrombosis (IVCT) is very rare, with only a few
      cases reported in the literature. While thromboembolism as a result of trauma is
      common in adult patients, it is very rare in young children and seldom involves
      the inferior vena cava. We report the youngest patient to date with IVCT and the
      only child reported whose findings are the result of child physical abuse. The
      diagnosis can be challenging both clinically and radiographically. Additionally,
      the risks of morbidity and even mortality associated with an IVCT if untreated
      are significant. 

PMID- 24578165
TI  - Seasonality updated in 28 European/Mediterranean countries: A continuing enigma.
AB  - OBJECTIVES: This report updates birth seasonality for 28 European/Mediterranean
      countries and evaluates the possible influence of atmospheric clarity/quality on
      seasonality. METHODS: Birth data between 1970 and 2011 were adjusted for
      seasonality and are presented as conceptions. RESULTS: Presently, 27 of 28
      countries have peak conceptions during the last 3 months of the year, a greater
      concentration than was previously recognized. CONCLUSIONS: There is no apparent
      explanation for the en masse transition of seasonality, particularly the abrupt
      change in seasonality for nine countries, The frequency of sexual intercourse
      might be a one determinant while another possibility might be the decadal changes
      in atmospheric clearness/quality. However, causal relationships cannot be
      inferred without further study and/or animal experimentation.

PMID- 24578164
TI  - Prognosis and response to therapy of first inpatient and outpatient heart failure
      event in a heart failure clinical trial: MADIT-CRT.
AB  - AIMS: Hospitalization for worsening heart failure (HF) is known to increase
      mortality and morbidity risk and has been frequently used as an endpoint in
      randomized clinical trials. Whether outpatient management of HF exacerbation
      carries similar prognostic and therapeutic information is less well known, but
      could be important for the design of trials that use HF hospitalization as an
      endpoint. METHODS AND RESULTS: MADIT-CRT randomized patients with mild HF
      symptoms to resynchronization therapy vs. control with an average follow-up of
      3.3 years and a total of 191 deaths. HF events were centrally adjudicated for
      receiving i.v. decongestive therapy in an outpatient setting, or an augmented HF
      regimen during a hospital stay. Patients were compared according to whether their
      first HF was an out- or inpatient event. The first primary event was non-fatal
      outpatient HF, non-fatal inpatient HF, and death in 52, 331, and 78 patients,
      respectively. Patients with inpatient HF tended to be older and more likely to
      have HF of ischaemic aetiology than subjects who developed outpatient HF events.
      The risk of death following either type of non-fatal HF events was extremely high
      [hazard ratio (HR) 12.4, 95% confidence interval (CI) 9.1-16.9 for inpatient HF;
      HR 10.7, 95% CI 6.1-18.7 for outpatient HF] compared with subjects without non
      fatal HF events. Allocation to CRT-D was associated with significant reduction in
      both types of HF. CONCLUSION: Outpatient management of worsening HF portends a
      high risk of death, similar to inpatient HF events, and may be equally sensitive
      to the effects of therapy. These findings suggest that outpatient HF events
      should be considered in publicly reported outcomes measures and future HF
      clinical trials. TRIAL REGISTRATION: NCT01294449.

PMID- 24578166
TI  - The nucleotide sequence and genome organization of two victoriviruses from the
      rice false smut fungus Ustilaginoidea virens.
AB  - Ustilaginoidea virens is the causal agent of false smut disease of rice. The
      dsRNA-Ls from a U. virens strain of Uv0901 containing three dsRNA bands were
      separated and sequenced. The dsRNA-Ls, with molecular weight of 5 kbp, were
      demonstrated to be two dsRNA segments referenced as dsRNA-L1 and dsRNA-L2. The
      two dsRNAs each contained two overlapped open reading frames, and showed
      significant similarity to those of capsid protein and RNA-directed RNA
      polymerase, respectively, of members of the family Totiviridae. Homology research
      and phylogenic analysis indicated that the dsRNA-L1 was a conspecific species of
      the previous reported Ustilaginoidea virens RNA virus 1, named Ustilaginoidea
      virens RNA virus Uv0901, and the dsRNA-L2 was a new number of the Victorivirus in
      the family Totiviridae, designed as Ustilaginoidea virens RNA virus 3.

PMID- 24578167
TI  - The effects of grandparents on children's schooling: evidence from rural China.
AB  - The issue of whether the social class of grandparents affects grandchildren's
      socioeconomic outcomes net of the characteristics of the middle generation is
      much debated in the social mobility literature. Using data from the 2002 Chinese
      Household Income Project, we investigate the direct effects of grandparents on
      grandchildren's educational attainment in rural China. We find that the influence
      of grandparents is contingent on living arrangements. Although the educational
      level of coresident grandparents directly affects the educational attainment of
      their grandchildren, with an effect size similar to that of parental education,
      the education of noncoresident and deceased grandparents does not have any
      effect. These findings suggest that grandparents can directly affect
      grandchildren's educational outcomes through sociopsychological pathways. Our
      study not only adds an important case study to the literature but also sheds new
      light on theoretical interpretations of grandparent effects when they are found. 

PMID- 24578168
TI  - Does education improve cognitive performance four decades after school
      completion?
AB  - We study the effect of secondary education on cognitive performance toward the
      end of working age. We exploit the exogenous variation in years of schooling
      arising from compulsory schooling reforms implemented in six European countries
      during the 1950s and 1960s. Using data of individuals, approximately age 60, from
      the Survey of Health, Ageing and Retirement in Europe (SHARE), we assess the
      causal effect of education on memory, fluency, numeracy, and orientation-to-date.
      Furthermore, we study education effects on cognitive decline. We find a positive
      impact of schooling on memory scores. One year of education increases the memory
      score approximately four decades later by about 0.2, which amounts to 10 % of a
      standard deviation. Furthermore, we find some evidence for a protective effect of
      schooling on cognitive decline in terms of verbal fluency. 

PMID- 24578169
TI  - Graphene oxide/alpha-Bi(2)O(3) composites for visible-light photocatalysis,
      chemical catalysis, and solar energy conversion.
AB  - The growing challenges of environmental purification by solar photocatalysis,
      precious-metal-free catalysis, and photocurrent generation in photovoltaic cells
      receive the utmost global attention. Here we demonstrate a one-pot, green
      chemical synthesis of a new stable heterostructured, ecofriendly, multifunctional
      microcomposite that consists of alpha-Bi2 O3 microneedles intercalated with
      anchored graphene oxide (GO) microsheets (1.0 wt %) for the above-mentioned
      applications on a large economical scale. The bare alpha-Bi2 O3 microneedles
      display two times better photocatalytic activities than commercial TiO2 (Degussa
      P25), whereas the GO-hybridized composite exhibits approximately four to six
      times enhanced photocatalytic activities than the neat TiO2 photocatalyst in the
      degradation of colored aromatic organic dyes (crystal violet and rhodamine 6G)
      under visible-light irradiation (300 W tungsten lamp). The highly efficient
      activity is associated with the strong surface adsorption ability of GO for
      aromatic dye molecules, the high carrier acceptability, and the efficient
      electron-hole pair separation in Bi2 O3 by individual adjoining GO sheets. The
      introduction of Ag nanoparticles (2.0 wt %) further enhances the photocatalytic
      performance of the composite over eightfold because of a plasmon-induced electron
      transfer process from Ag nanoparticles through the GO sheets into the conduction
      band of Bi2 O3 . The new composites are also catalytically active and catalyze
      the reduction of 4-nitrophenol to 4-aminophenol in the presence of borohydride
      ions. Photoanodes assembled from GO/alpha-Bi2 O3 and Ag/GO/alpha-Bi2 O3
      composites display an improved photocurrent response (power conversion efficiency
      ~20 % higher) over those prepared without GO in dye-sensitized solar cells. 

PMID- 24578170
TI  - Radio frequency identification (RFID) in health care: privacy and security
      concerns limiting adoption.
AB  - Radio frequency identification (RFID) technology has been implemented in a wide
      variety of industries. Health care is no exception. This article explores
      implementations and limitations of RFID in several health care domains:
      authentication, medication safety, patient tracking, and blood transfusion
      medicine. Each domain has seen increasing utilization of unique applications of
      RFID technology. Given the importance of protecting patient and data privacy,
      potential privacy and security concerns in each domain are discussed. Such
      concerns, some of which are inherent to existing RFID hardware and software
      technology, may limit ubiquitous adoption. In addition, an apparent lack of
      security standards within the RFID domain and specifically health care may also
      hinder the growth and utility of RFID within health care for the foreseeable
      future. Safeguarding the privacy of patient data may be the most important
      obstacle to overcome to allow the health care industry to take advantage of the
      numerous benefits RFID technology affords. 

PMID- 24578171
TI  - Effect of perioperative transfusion of old red blood cells on postoperative
      complications after free muscle sparing transverse rectus abdominis myocutaneous
      flap surgery for breast reconstruction.
AB  - BACKGROUND: Transfusion with old red blood cells (RBCs) was associated with
      adverse clinical outcomes. The effect of perioperative transfusion of old RBCs on
      postoperative complications after free muscle sparing transverse rectus abdominis
      myocutaneous (TRAM) flap surgery was retrospectively investigated. METHODS: Two
      hundred sixty-one patients undergoing breast reconstruction were assigned to two
      groups: no transfusion and transfusion groups. Transfused patients were further
      divided according to the RBC storage duration (fresh, <=14 days; old, >14 days).
      Postoperative complications such as vascular thrombosis, hematoma, and flap
      congestion were noted. RESULTS: Patients who received old blood (n = 34),
      compared with those received fresh blood (n = 40) or no transfusion (n = 187),
      had a higher incidence of postoperative complications (44.1% vs. 20.0% or 12.8%,
      P < 0.05). CONCLUSIONS: Perioperative transfusion of old RBCs can be associated
      with an increase in postoperative complications after free muscle sparing TRAM
      flap surgery.

PMID- 24578172
TI  - Screening for hip dysplasia in congenital muscular torticollis: is physical exam
      enough?
AB  - PURPOSE: An association between congenital muscular torticollis (CMT) and
      developmental dysplasia of the hip (DDH) has been established in the literature;
      however, whether the screening of patients with CMT for DDH requires hip imaging
      remains controversial. The purpose of this study is to determine (1) the
      coexistence rate of DDH requiring treatment in individuals with CMT and (2) if
      physical exam alone is sufficient screening. METHODS: A single-center
      retrospective chart review was performed among 97 consecutive patients between
      1/1/2003 and 9/1/2012 with CMT who had hip imaging performed. RESULTS: 12 %
      (12/97) of patients with CMT had DDH, all requiring treatment. 75 % (9/12) of the
      patients with DDH had an abnormal clinical exam. Of the three patients with DDH
      and a normal clinical exam, two patients were presenting for a second opinion
      after being treated for DDH prior to evaluation. 90 % (9/10) of patients with DDH
      at the time of presentation had an abnormal hip exam. All 12 patients with hip
      dysplasia were referred for DDH or DDH with CMT. There were no patients who were
      referred for CMT alone that had DDH. CONCLUSIONS: In the care of a patient with
      CMT, it is important that the clinician remains vigilant about screening for DDH.
      An ultrasound or radiograph of the hips should be strongly considered as part of
      the evaluation of a child with CMT. LEVEL OF EVIDENCE: IV.

PMID- 24578173
TI  - Caveolin-1 deficiency may predispose African Americans to systemic sclerosis
      related interstitial lung disease.
AB  - OBJECTIVE: Interstitial lung disease (ILD) is the leading cause of death in
      patients with systemic sclerosis (SSc; scleroderma). Although SSc-related ILD is
      more common and severe in African Americans than in Caucasians, little is known
      about factors underlying this significant health disparity. The aim of this study
      was to examine the role that low expression of caveolin-1 might play in
      susceptibility to ILD among African Americans. METHODS: Assays of monocyte
      migration toward stromal cell-derived factor 1 (SDF-1) were performed using
      monocytes from Caucasian and African American healthy donors and patients with
      SSc. For fibrocyte differentiation studies, total peripheral blood mononuclear
      cells were incubated on fibronectin-coated plates. Protein expression was
      evaluated by immunohistochemistry and Western blotting. RESULTS: Monocytes from
      healthy African American donors and those from patients with SSc had low caveolin
      1 levels, enhanced migration toward the CXCR4 ligand SDF-1, and enhanced
      differentiation to fibrocytes. Enhanced migration and differentiation of
      monocytes from African Americans and patients with SSc appeared to be
      attributable to the lack of caveolin-1, because restoring caveolin-1 function
      using a caveolin-1 scaffolding domain peptide inhibited these processes. Although
      they differed from monocytes from Caucasians, monocytes from both African
      Americans and patients with SSc were not identical, because SSc monocytes showed
      major increases from baseline in ERK, JNK, p38, and Smad2/3 activation, while
      monocytes from African Americans showed only limited ERK activation and no
      activation of JNK, p38, or Smad2/3. In contrast, SDF-1 exposure caused no
      additional ERK activation in SSc monocytes but did cause significant additional
      activation in monocytes from African Americans. CONCLUSION: African Americans may
      be predisposed to SSc-related ILD due to low baseline caveolin-1 levels in their
      monocytes, potentially affecting signaling, migration, and fibrocyte
      differentiation. The monocytes of African Americans may lack caveolin-1 due to
      high levels of transforming growth factor beta in their blood.

PMID- 24578175
TI  - Fluorescence immunoassay of human D-dimer in whole blood.
AB  - BACKGROUND: D-dimer is a widely used biomarker for the initial clinical
      assessment of suspected deep vein thrombosis and pulmonary embolism. Here, we
      presented a new fluorescence (FL) D-dimer assay system, which was developed with
      a platform of point-of-care test (POCT) for clinical applications. METHODS: Whole
      blood was mixed with FL-labeled anti-D-dimer detector antibody, and then loaded
      onto a disposable cartridge. After 12 min of incubation, the FL intensity was
      acquired by scanning of test cartridge and converted as level of D-dimer in a
      laser FL scanner. The analytical performance of FL immunoassay was evaluated by
      linearity, recovery, and precision tests. The comparability of the developed
      assay was examined with automated reference methods. RESULTS: The FL assay system
      showed a good linearity, and the analytical mean recovery of control was 103% in
      a dynamic working range. The imprecision of intra- and inter-as-say of
      coefficient of variations from assay system was less than 8%. The developed FL
      assay system showed strong correlation with two automated reference assays, Vidas
      D-dimer (r = 0.973) and Stalia D-dimer (r = 0.971). CONCLUSION: The new FL
      immunoassay for D-dimer is a user-friendly, precise, and reproducible platform of
      POCT in whole blood.

PMID- 24578176
TI  - Recurrent mutation testing of BRCA1 and BRCA2 in Asian breast cancer patients
      identify carriers in those with presumed low risk by family history.
AB  - Although the breast cancer predisposition genes BRCA1 and BRCA2 were discovered
      more than 20 years ago, there remains a gap in the availability of genetic
      counselling and genetic testing in Asian countries because of cost, access and
      inaccurate reporting of family history of cancer. In order to improve access to
      testing, we developed a rapid test for recurrent mutations in our Asian
      populations. In this study, we designed a genotyping assay with 55 BRCA1 and 44
      BRCA2 mutations previously identified in Asian studies, and validated this assay
      in 267 individuals who had previously been tested by full sequencing. We tested
      the prevalence of these mutations in additional breast cancer cases. Using this
      genotyping approach, we analysed recurrent mutations in 533 Malaysian breast
      cancer cases with <10 % a priori risk, and found 1 BRCA1 (0.2 %) and 5 BRCA2 (0.9
      %) carriers. Testing in a hospital-based unselected cohort of 532 Singaporean
      breast cancer cases revealed 6 BRCA1 (1.1 %) and 3 BRCA2 (0.6 %) carriers.
      Overall, 2 recurrent BRCA1 and 1 BRCA2 mutations in Malays, 3 BRCA1 and 2 BRCA2
      mutations in Chinese and 1 BRCA1 mutation in Indians account for 60, 24 and 20 %
      of carrier families, respectively. By contrast, haplotype analyses suggest that a
      recurrent BRCA2 mutation (c.262_263delCT) found in 5 unrelated Malay families has
      at least 3 distinct haplotypes. Taken together, our data suggests that panel
      testing may help to identify carriers, particularly Asian BRCA2 carriers, who do
      not present with a priori strong family history characteristics.

PMID- 24578178
TI  - Impacts of PICALM and CLU variants associated with Alzheimer's disease on the
      functional connectivity of the hippocampus in healthy young adults.
AB  - PICALM rs3851179 and CLU rs11136000 have been recently associated with
      Alzheimer's disease (AD). Investigating the effects of these genetic variants on
      the resting-state functional connectivity (rsFC) of the hippocampus may provide
      new insight into AD pathogenesis. We investigated the main effects and
      interactions of these two genetic variants on hippocampal rsFC in 283 healthy
      young adults. The hippocampus showed positive rsFC with the default mode network
      and negative rsFC with the fronto-parietal network. Risk PICALM G-allele carriers
      showed weaker negative rsFC compared with AA carriers, whereas risk CLU-CC
      carriers exhibited stronger positive and negative rsFC than T-allele carriers.
      There existed complex interactions between PICALM and CLU on the negative rsFC of
      the hippocampus. Moreover, we found an allele-dependent effect of CLU on
      hippocampal connectivity when an additive genetic model was applied to CLU. Most
      of these effects remained significant even after controlling for individual ApoE
      status. Our results suggest that PICALM and CLU risk genotypes exert differential
      impacts on the hippocampal rsFC in healthy young subjects. The complex
      interactions between PICALM and CLU should be considered when investigating the
      impact of these two genetic variants on the brain. 

PMID- 24578179
TI  - Recent multidisciplinary approach with molecular targeted drugs for advanced head
      and neck cancer.
AB  - The multidisciplinary approach is becoming the standard for treatment of advanced
      head and neck cancer. Combined modality treatment preserves quality of life as
      well as improving the length of survival time. Molecular targeted drugs have
      become very important in the multidisciplinary approach for the treatment of
      advanced head and neck cancer. Cetuximab has been shown to have locoregional
      control and additional survival benefits in locally advanced squamous cell
      carcinoma of the head and neck as well as additional survival benefits in distant
      metastatic/recurrent squamous cell carcinoma of the head and neck. Recently, many
      clinical studies of the multidisciplinary approach including cetuximab have been
      carried out in Europe and the US. It has been shown that cetuximab in combination
      with radiotherapy (RT) is significantly superior to the RT alone in median
      locoregional control duration and median overall survival (OS). For recurrent or
      metastatic disease, the results of a phase III randomized control study of CDDP +
      5-fluorouracil combination therapy with or without cetuximab reported that OS was
      significantly longer with than without cetuximab, demonstrating an additional
      survival benefit of cetuximab. Many trials including induction chemotherapy are
      being conducted. Clinical trials with cetuximab have also been conducted in
      Japan. Though combination with cetuximab shows some benefit, further studies are
      necessary to obtain the standard treatments for a multidisciplinary approach for
      advanced head and neck cancer.

PMID- 24578177
TI  - Corticolimbic catecholamines in stress: a computational model of the appraisal of
      controllability.
AB  - Appraisal of a stressful situation and the possibility to control or avoid it is
      thought to involve frontal-cortical mechanisms. The precise mechanism underlying
      this appraisal and its translation into effective stress coping (the regulation
      of physiological and behavioural responses) are poorly understood. Here, we
      propose a computational model which involves tuning motivational arousal to the
      appraised stressing condition. The model provides a causal explanation of the
      shift from active to passive coping strategies, i.e. from a condition
      characterised by high motivational arousal, required to deal with a situation
      appraised as stressful, to a condition characterised by emotional and
      motivational withdrawal, required when the stressful situation is appraised as
      uncontrollable/unavoidable. The model is motivated by results acquired via
      microdialysis recordings in rats and highlights the presence of two competing
      circuits dominated by different areas of the ventromedial prefrontal cortex:
      these are shown having opposite effects on several subcortical areas, affecting
      dopamine outflow in the striatum, and therefore controlling motivation. We start
      by reviewing published data supporting structure and functioning of the neural
      model and present the computational model itself with its essential neural
      mechanisms. Finally, we show the results of a new experiment, involving the
      condition of repeated inescapable stress, which validate most of the model's
      predictions. 

PMID- 24578180
TI  - Cytokine profile in cervical mucosa of Japanese patients with cervical
      intraepithelial neoplasia.
AB  - BACKGROUND: Immune responses in the uterine cervix are considered to play an
      important role in persistent human papillomavirus (HPV) infection and
      carcinogenesis, but many aspects of the mechanism are still unclear. The goal of
      this study was to measure cytokines to analyze immune responses in patients with
      cervical intraepithelial neoplasia (CIN). MATERIALS AND METHODS: The levels of 17
      cytokines (IL-1beta, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, IL
      17, G-CSF, GM-CSF, INF-gamma, MCP-1, MIP-1beta, and TNFalpha) in cervical mucus
      were simultaneously measured using a multiplex immunoassay in 52 high-grade
      squamous intraepithelial lesion (HSIL) cases and overproduction of IL-1beta, IL
      8, and MIP-1beta was identified. The levels of these 3 cytokines were measured in
      130 patients with or without CIN lesions using enzyme-linked immunosorbent assay.
      The associations of the cytokine levels with the cytology, infecting HPV type,
      and status of cigarette smoking were investigated. RESULTS: IL-1beta and IL-8
      levels were associated with the cytology, and these levels were higher in HSIL
      cases than in NILM (negative for intraepithelial lesion and malignancy) and LSIL
      (low-grade squamous intraepithelial lesion) cases (P = 0.005, P = 0.001,
      respectively). The MIP-1beta level was significantly lower in smokers (P = 0.018)
      and high-risk (HR)-HPV-infected patients (P = 0.021). CONCLUSIONS: Enhanced
      expression of IL-1beta and IL-8 indicates that Th2 inflammatory responses become
      stronger in the local uterine cervical region with the progression of CIN
      lesions, and a decrease in the MIP-1beta level may be advantageous for
      immunoescape of HPV. Cigarette smoking may further facilitate persistent HPV
      infection.

PMID- 24578174
TI  - Glutamate as a neurotransmitter in the healthy brain.
AB  - Glutamate is the most abundant free amino acid in the brain and is at the
      crossroad between multiple metabolic pathways. Considering this, it was a
      surprise to discover that glutamate has excitatory effects on nerve cells, and
      that it can excite cells to their death in a process now referred to as
      "excitotoxicity". This effect is due to glutamate receptors present on the
      surface of brain cells. Powerful uptake systems (glutamate transporters) prevent
      excessive activation of these receptors by continuously removing glutamate from
      the extracellular fluid in the brain. Further, the blood-brain barrier shields
      the brain from glutamate in the blood. The highest concentrations of glutamate
      are found in synaptic vesicles in nerve terminals from where it can be released
      by exocytosis. In fact, glutamate is the major excitatory neurotransmitter in the
      mammalian central nervous system. It took, however, a long time to realize that.
      The present review provides a brief historical description, gives a short
      overview of glutamate as a transmitter in the healthy brain, and comments on the
      so-called glutamate-glutamine cycle. The glutamate transporters responsible for
      the glutamate removal are described in some detail. 

PMID- 24578182
TI  - Physicochemical properties and membrane biofouling of extra-cellular
      polysaccharide produced by a Micrococcus luteus strain.
AB  - The physicochemical properties of the extra-cellular polysaccharide (EPS)
      produced by a Micrococcus luteus strain, a dominating strain isolated from
      membrane biofouling layer, were determined in this study. The EPS isolated from
      this strain was measured to have an average molecular weight of 63,540 Da and
      some typical polysaccharide absorption peaks in Fourier transform infrared
      spectrum. Monosaccharide components of the EPS contained rhamnose, fucose,
      arabinose, xylose, mannose, galactose and glucose in a molar ratio of
      0.2074:0.0454:0.0262:0.0446:1.7942:1.2086:0.4578. Pseudo plastic properties were
      also observed for the EPS through the rheological measurement. The EPS was
      further characterized for its behavior to cause membrane flux decline. The
      results showed that both flux declines for polyvinylidenefluoride (PVDF) and
      polypropylene membranes became more severe as EPS feed concentration increased. A
      higher irreversible fouling for the PVDF membrane suggested that the EPS had the
      larger fouling potential to this microfiltration membrane.

PMID- 24578181
TI  - New insights into FAK function and regulation during spermatogenesis.
AB  - Germ cell transport across the seminiferous epithelium during the epithelial
      cycle is crucial to spermatogenesis, although molecular mechanism(s) that
      regulate these events remain unknown. Studies have shown that spatiotemporal
      expression of crucial regulatory proteins during the epithelial cycle represents
      an efficient and physiologically important mechanism to regulate spermatogenesis
      without involving de novo synthesis of proteins and/or expression of genes.
      Herein, we critically review the role of focal adhesion kinase (FAK) in
      coordinating the transport of spermatids and preleptotene spermatocytes across
      the epithelium and the BTB, respectively, along the apical ectoplasmic
      specialization (ES) - blood-testis barrier - basement membrane (BM) functional
      axis during spermatogenesis. In the testis, p-FAK-Tyr&#179;&#8312;&#8311; and p
      FAK-Tyr&#8308;&#8304;&#8311; are spatiotemporally expressed during the epithelial
      cycle at the actin-rich anchoring junction known as ES, regulating cell adhesion
      at the Sertoli-spermatid (apical ES) and Sertoli cell-cell (basal ES) interface.
      Phosphorylated forms of FAK exert their effects by regulating the homeostasis of
      F-actin at the ES, mediated via their effects on actin polymerization so that
      microfilaments are efficiently re-organized, such as from their "bundled" to "de
      bundled/branched" configuration and vice versa during the epithelial cycle to
      facilitate the transport of: (i) spermatids across the epithelium, and (ii)
      preleptotene spermatocytes across the BTB. In summary, p-FAK
      Tyr&#8308;&#8304;&#8311; and p-FAK-Tyr&#179;&#8312;&#8311; are important
      regulators of spermatogenesis which serve as molecular switches that turn "on"
      and "off" adhesion function at the apical ES and the basal ES/BTB, mediated via
      their spatiotemporal expression during the epithelial cycle. A hypothetical model
      depicting the role of these two molecular switches is also proposed.

PMID- 24578183
TI  - Altered structural brain connectome in young adult fragile X premutation
      carriers.
AB  - Fragile X premutation carriers (fXPC) are characterized by 55-200 CGG
      trinucleotide repeats in the 5' untranslated region on the Xq27.3 site of the X
      chromosome. Clinically, they are associated with the fragile X-Associated
      Tremor/Ataxia Syndrome, a late-onset neurodegenerative disorder with diffuse
      white matter neuropathology. Here, we conducted first-ever graph theoretical
      network analyses in fXPCs using 30-direction diffusion-weighted magnetic
      resonance images acquired from 42 healthy controls aged 18-44 years (HC; 22 male
      and 20 female) and 46 fXPCs (16 male and 30 female). Globally, we found no
      differences between the fXPCs and HCs within each gender for all global graph
      theoretical measures. In male fXPCs, global efficiency was significantly
      negatively associated with the number of CGG repeats. For nodal measures,
      significant group differences were found between male fXPCs and male HCs in the
      right fusiform and the right ventral diencephalon (for nodal efficiency), and in
      the left hippocampus [for nodal clustering coefficient (CC)]. In female fXPCs, CC
      in the left superior parietal cortex correlated with counting performance in an
      enumeration task.

PMID- 24578185
TI  - Biosimilar granulocyte colony-stimulating factor uptakes in the EU-5 markets: a
      descriptive analysis.
AB  - BACKGROUND: Biosimilars are copies of biological reference medicines. Unlike
      generics (copies of chemical molecules), biologics are complex, expensive and
      complicated to produce. The knowledge of the factors affecting the competition
      following patent expiry for biologics remains limited. OBJECTIVES: The aims of
      this study were to analyse the EU-5 Granulocyte-Colony Stimulating Factor (G-CSF)
      markets and to determine the factors affecting the G-CSF biosimilar uptakes,
      particularly that of biosimilar prices relative to originators. METHODS: Data on
      medicine volumes, values, and ex-manufacturer prices for all G-CSF categories
      were provided by IMS Health. Volumes were calculated in defined daily doses (DDD)
      and prices in Euros per DDD. In the EU-5 countries, there is 5 years of
      experience with biosimilar G-CSFs (2007-2011). RESULTS: Two G-CSF market profiles
      exist: (1) countries with a high retail market distribution, which are the
      largest G-CSF markets with low global G-CSF biosimilar uptakes (5.4% in France
      and 8.5% in Germany in 2011); and (2) countries with a dominant hospital channel,
      which are the smallest markets with higher G-CSF biosimilar uptakes (12.4% in
      Spain and 20.4% in the UK). The more the decisions are decentralized, the more
      their uptakes are high. The price difference between G-CSF biosimilars and their
      reference plays a marginal role at a global level (price differences of +13.3% in
      the UK and -20.4% in France). CONCLUSION: The competition with G-CSF biosimilars
      varies significantly between EU-5 countries, probably because of G-CSF
      distribution channel differences. Currently, this competition is not mainly based
      on prices, but on local political options to stimulate tendering between them and
      recently branded second- or third-generation products.

PMID- 24578184
TI  - Cancer gene therapy using mesenchymal stem cells.
AB  - Cellular and gene therapies represent promising treatment strategies at the
      frontier of medicine. Hematopoietic stem cells, lymphocytes, and mesenchymal stem
      cells (MSCs) can all serve as sources of cells for use in such therapies.
      Strategies for gene therapy are often based on those of cell therapy, and it is
      anticipated that some examples will be put to practical use in the near future.
      Given their ability to support hematopoiesis, MSCs may be useful for the
      enhancement of stem cell engraftment, and the acceleration of hematopoietic
      reconstitution. Furthermore, MSCs may advance the treatment of severe graft
      versus-host disease, based on their immunosuppressive ability. This application
      is also based on the homing behavior of MSCs to sites of injury and inflammation.
      Interestingly, MSCs possess tumor-homing ability, opening up the possibility of
      applications in the targeted delivery of anti-cancer genes to tumors. Many
      reports have indicated that MSCs can be utilized to target tumors and to deliver
      anti-cancer molecules locally, as tumors are recognized as non-healing wounds
      with inflammatory tissue. Here, we review both the potential of MSCs as cellular
      vehicles for targeted cancer therapy and the molecular mechanisms underlying MSC
      accumulation at tumor sites. 

PMID- 24578186
TI  - Urine L-carnitine excretion in hypertensive adolescents.
AB  - AIM: This study was performed to test the hypothesis that urinary levels of L
      carnitine and its derivatives are enhanced in children and adolescents with
      hypertension and also check if analyzed parameters may serve as early markers of
      subclinical renal damage. METHODS: The study included 112 children and
      adolescents (67 males and 45 females) aged median 10-18 years. Participants were
      divided into two groups: HT-64 subjects with confirmed primary hypertension and R
      reference group-48 subjects with white-coat hypertension. Urinary Free and Total
      L-carnitine were determined by the enzymatic method of Cederblad. The L-carnitine
      levels were expressed as urinary ratio in micromole per gram creatinine
      (MUmol/g). RESULTS: The urinary excretion of Total and Free L-carnitine was
      significantly higher in hypertensive adolescents in comparison to reference group
      white coat hypertension. Other important findings were positive correlations
      between Free L-carnitine/cr., Total L-carnitine/cr. ratio and serum uric acid
      level, serum cholesterol level and systolic blood pressure. CONCLUSION: The
      results of this study do not explain the increased urine levels of L-carnitine.
      The most likely reason for excessive urinary loss was disturbed renal tubular
      reabsorption. It is possible to hypothesize that in hypertensive adolescents
      subclinical kidney dysfunction occurs. It is proposed that studies examining the
      concurrent plasma and urine concentration of L-carnitine and correlation with
      acknowledged proximal tubular markers are needed.

PMID- 24578188
TI  - Propylene from renewable resources: catalytic conversion of glycerol into
      propylene.
AB  - Propylene, one of the most demanded commodity chemicals, is obtained
      overwhelmingly from fossil resources. In view of the diminishing fossil resources
      and the ongoing climate change, the identification of new efficient and
      alternative routes for the large-scale production of propylene from biorenewable
      resources has become essential. Herein, a new selective route for the synthesis
      of propylene from bio-derived glycerol is demonstrated. The route consists of the
      formation of 1-propanol (a versatile bulk chemical) as intermediate through
      hydrogenolysis of glycerol at a high selectivity. A subsequent dehydration
      produces propylene. 

PMID- 24578189
TI  - On the accuracy of T1 mapping: searching for common ground.
AB  - PURPOSE: There are many T1 mapping methods available, each of them validated in
      phantoms and reporting excellent agreement with literature. However, values in
      literature vary greatly, with T1 in white matter ranging from 690 to 1100 ms at 3
      Tesla. This brings into question the accuracy of one of the most fundamental
      measurements in quantitative MRI. Our goal was to explain these variations and
      look into ways of mitigating them. THEORY AND METHODS: We evaluated the three
      most common T1 mapping methods (inversion recovery, Look-Locker, and variable
      flip angle) through Bloch simulations, a white matter phantom and the brains of
      10 healthy subjects (single-slice). We pooled the T1 histograms of the subjects
      to determine whether there is a sequence-dependent bias and whether it is
      reproducible across subjects. RESULTS: We found good agreement between the three
      methods in phantoms, but poor agreement in vivo, with the white matter T1
      histogram peak in healthy subjects varying by more than 30% depending on the
      method used. We also found that the pooled brain histograms displayed three
      distinct white matter peaks, with Look-Locker consistently underestimating, and
      variable flip angle overestimating the inversion recovery T1 values. The Bloch
      simulations indicated that incomplete spoiling and inaccurate B1 mapping could
      account for the observed differences. CONCLUSION: We conclude that the three most
      common T1 mapping protocols produce stable T1 values in phantoms, but not in
      vivo. To improve the accuracy of T1 mapping, we recommend that sites perform in
      vivo validation of their T1 mapping method against the inversion recovery
      reference method, as the first step toward developing a robust calibration
      scheme.

PMID- 24578187
TI  - Preclinical PK/PD modeling and human efficacious dose projection for a
      glucokinase activator in the treatment of diabetes.
AB  - Human Hexokinase IV, or glucokinase (GK), is a regulator of glucose
      concentrations in the body. It plays a key role in pancreatic insulin secretion
      as well as glucose biotransformation in the liver, making it a potentially viable
      target for treatment of Type 2 diabetes. Allosteric activators of GK have been
      shown to decrease blood glucose concentrations in both animals and humans. Here,
      the development of a mathematical model is presented that describes glucose
      modulation in an ob/ob mouse model via administration of a potent GK activator,
      with the goal of projecting a human efficacious dose and plasma exposure. The
      model accounts for the allosteric interaction between GK, the activator, and
      glucose using a modified Hill function. Based on model simulations using data
      from the ob/ob mouse and in vitro studies, human projections of glucose response
      to the GK activator are presented, along with dose and regimen predictions to
      maintain clinically significant decreases in blood glucose in a Type 2 diabetic
      patient. This effort serves as a basis to build a detailed mechanistic
      understanding of GK and its role as a therapeutic target for Type 2 diabetes, and
      it highlights the benefits of using such an approach in a drug discovery setting.

PMID- 24578191
TI  - L-cysteine-induced fabrication of spherical titania nanoparticles within
      poly(ether-imide) matrix.
AB  - In the presented study, a new L-cysteine-containing diamine is synthesized and
      fully characterized and its application for the in situ sol-gel fabrication of
      poly(ether-imide)/titania nano hybrid materials is investigated. The electron
      microscopic photographs (TEM, FE-SEM and AFM) of the resulted materials confirm
      the production of spherical nanoparticles with well dispersion and narrow
      particle size distribution which is a usual challenge in the sol-gel methods. In
      addition to the positive effects on the particles morphology, the existence of
      amino acid containing pendant groups in the structure of polymer chains led to
      the comprehensive interaction with titania phase. As a result, the improvement in
      the flexibility of polymer backbone (as one of the most serious difficulties in
      polyimides processing) is obtained while its thermal stability dose is not
      sacrificed (confirmed by TGA and DSC techniques). 

PMID- 24578190
TI  - Proinflammatory adaptive cytokine and shed tumor necrosis factor receptor levels
      are elevated preceding systemic lupus erythematosus disease flare.
AB  - OBJECTIVE: Systemic lupus erythematosus (SLE) is a multifaceted disease
      characterized by immune dysregulation and unpredictable disease activity. This
      study sought to evaluate the changes in plasma concentrations of soluble
      mediators that precede clinically defined disease flares. METHODS: Fifty-two
      different soluble mediators, including cytokines, chemokines, and soluble
      receptors, were examined using validated multiplex bead-based or enzyme-linked
      immunosorbent assays in plasma from 28 European American patients with SLE who
      developed disease flare 6 or 12 weeks after a baseline assessment (preflare), 28
      matched SLE patients without impending flare (nonflare), and 28 matched healthy
      controls. In a subset of 13 SLE patients, mediators within samples obtained
      preceding disease flare were compared with those within samples from the same
      individual obtained during a clinically stable period without flare. RESULTS:
      Compared to SLE patients with clinically stable disease, SLE patients with
      impending flare had significant alterations (P <= 0.01) in the levels of 27
      soluble mediators at baseline; specifically, the levels of proinflammatory
      mediators, including Th1-, Th2-, and Th17-type cytokines, were significantly
      higher several weeks before clinical flare. Baseline levels of regulatory
      cytokines, including interleukin-10 and transforming growth factor beta, were
      higher in nonflare SLE patients, whereas baseline levels of soluble tumor
      necrosis factor receptor type I (TNFRI), TNFRII, Fas, FasL, and CD40L were
      significantly higher (P <= 0.002) in preflare SLE patients. The normalized and
      weighted combined soluble mediator score was significantly higher (P <= 0.0002)
      in preflare samples from SLE patients compared to samples from the same patients
      obtained during periods of stable disease. CONCLUSION: The levels of
      proinflammatory adaptive cytokines and shed TNF receptors are elevated prior to
      disease flare, while the levels of regulatory mediators are elevated during
      periods of stable disease. Alterations in the balance between inflammatory and
      regulatory mediators may help identify patients at risk of disease flare and help
      decipher the pathogenic mechanisms of SLE.

PMID- 24578193
TI  - Development and evaluation of statistical shape modeling for principal inner
      organs on torso CT images.
AB  - The shapes of the inner organs are important information for medical image
      analysis. Statistical shape modeling provides a way of quantifying and measuring
      shape variations of the inner organs in different patients. In this study, we
      developed a universal scheme that can be used for building the statistical shape
      models for different inner organs efficiently. This scheme combines the
      traditional point distribution modeling with a group-wise optimization method
      based on a measure called minimum description length to provide a practical means
      for 3D organ shape modeling. In experiments, the proposed scheme was applied to
      the building of five statistical shape models for hearts, livers, spleens, and
      right and left kidneys by use of 50 cases of 3D torso CT images. The performance
      of these models was evaluated by three measures: model compactness, model
      generalization, and model specificity. The experimental results showed that the
      constructed shape models have good "compactness" and satisfied the
      "generalization" performance for different organ shape representations; however,
      the "specificity" of these models should be improved in the future.

PMID- 24578195
TI  - New sections for Techniques in Coloproctology and other announcements.

PMID- 24578192
TI  - The mu-opioid receptor agonist/noradrenaline reuptake inhibition (MOR-NRI)
      concept in analgesia: the case of tapentadol.
AB  - Tapentadol is a novel, centrally-acting analgesic drug, with an analgesic
      efficacy comparable to that of strong opioids such as oxycodone and morphine. Its
      high efficacy has been demonstrated in a range of animal models of acute and
      chronic, nociceptive, inflammatory, and neuropathic pain as well as in clinical
      studies with moderate to severe pain arising from a number of different
      etiologies. At the same time, a favorable gastrointestinal tolerability has been
      demonstrated in rodents and humans, and advantages over morphine regarding
      tolerance development and physical dependence were shown in animal studies.
      Furthermore, a low level of abuse and diversion is beginning to emerge from first
      post-marketing data. Tapentadol acts as a MU-opioid receptor (MOR) agonist and
      noradrenaline reuptake inhibitor (NRI). Both mechanisms of action have been shown
      to contribute to the analgesic activity of tapentadol and to produce analgesia in
      a synergistic manner, such that relatively moderate activity at the two target
      sites (MOR and noradrenaline reuptake transporter) is sufficient to produce
      strong analgesic effects. It has been suggested that tapentadol is the first
      representative of a proposed new class of analgesics, MOR-NRI. This review
      presents the evidence that has led to this suggestion, and outlines how the
      pharmacology of tapentadol can explain its broad analgesic activity profile and
      high analgesic potency as well as its favorable tolerability. 

PMID- 24578197
TI  - High-grade angiosarcoma of the right atrium successfully targeted with total
      resection and reconstruction followed by adjuvant chemotherapy.

PMID- 24578198
TI  - Intravenous therapies in acute heart failure-lack of effect or lack of well
      powered studies?

PMID- 24578199
TI  - Totally percutaneous versus standard femoral artery access for elective
      bifurcated abdominal endovascular aneurysm repair.
AB  - BACKGROUND: Abdominal aortic aneurysms (AAAs) are a vascular condition with
      significant risk attached, particularly if they rupture. It is, therefore,
      critical to identify and repair these as an elective procedure before they
      rupture and require emergency surgery. Repair has traditionally been an open
      surgical technique that required a large incision across the abdomen. More
      recently endovascular aneurysm repairs (EVARs) have become a common alternative.
      In this procedure, the common femoral artery is exposed via a cut-down approach
      and a graft is introduced to the aneurysm in this way. This review examines a
      totally percutaneous approach to EVAR. This technique gives a minimally invasive
      approach to femoral artery access that may reduce groin wound complication rates
      and improve recovery time. The technique may, however, be less applicable in
      patients with, for example, groin scarring or arterial calcification. OBJECTIVES:
      This review aims to compare the clinical outcomes of percutaneous access with
      standard femoral artery access in elective bifurcated abdominal endovascular
      aneurysm repair (EVAR). SEARCH METHODS: The Cochrane Peripheral Vascular Diseases
      Group Trials Search Co-ordinator searched their Specialised Register (last
      searched July 2013), CENTRAL (2013, Issue 6) and clinical trials databases.
      Reference lists of retrieved articles were checked. SELECTION CRITERIA: Only
      randomised controlled trials were considered. The primary intervention was a
      totally percutaneous endovascular repair. All device types were considered. This
      was compared against standard femoral artery endovascular repair. Only studies
      investigating elective repairs were considered. Studies reporting emergency
      surgery for a ruptured abdominal aortic aneurysm (rAAA) and those reporting aorto
      uni-iliac repairs were excluded. DATA COLLECTION AND ANALYSIS: All data were
      collected independently by two review authors. Owing to the small number of
      trials identified, no formal assessment of heterogeneity or sensitivity analysis
      was conducted. MAIN RESULTS: Only one trial met the inclusion criteria, involving
      a total of 30 participants, 15 undergoing the percutaneous technique and 15
      treated by the standard femoral cut-down approach. There were no significant
      differences between the two groups at baseline.No mortality or failure of
      aneurysm exclusion was observed in either group. Three wound infections occurred
      in the standard femoral cut-down group, whereas none were observed in the
      percutaneous group. This was not statistically significant. Only one major
      complication was observed in the study, a conversion to the cut-down technique in
      the percutaneous access group. No long-term outcomes were reported. One episode
      of a bleeding complication was reported in the percutaneous group. Significant
      differences were detected in surgery time (percutaneous 86.7 +/- 27 minutes
      versus conventional 107.8 +/- 38.5 minutes; P < 0.05).The included study had a
      small sample size and failed to report adequately the method of randomisation,
      allocation concealment and the pre-selected outcomes. AUTHORS' CONCLUSIONS: Only
      one small study was identified, which did not provide adequate evidence to
      determine the efficacy and safety of the percutaneous approach compared with
      endovascular aneurysm repairs. This review has identified a clear need for
      further research into this potentially beneficial technique. One ongoing study
      was identified in the search, which may provide an improved evidence base in the
      future.

PMID- 24578196
TI  - Placebo analgesia and reward processing: integrating genetics, personality, and
      intrinsic brain activity.
AB  - Our expectations about an event can strongly shape our subjective evaluation and
      actual experience of events. This ability, applied to the modulation of pain, has
      the potential to affect therapeutic analgesia substantially and constitutes a
      foundation for non-pharmacological pain relief. A typical example of such
      modulation is the placebo effect. Studies indicate that placebo may be regarded
      as a reward, and brain activity in the reward system is involved in this
      modulation process. In the present study, we combined resting-state functional
      magnetic resonance imaging (rs-fMRI) measures, genotype at a functional COMT
      polymorphism (Val158Met), and personality measures in a model to predict the
      magnitude of placebo conditioning effect indicated by subjective pain rating
      reduction to calibrated noxious stimuli. We found that the regional homogeneity
      (ReHo), an index of local neural coherence, in the ventral striatum, was
      significantly associated with conditioning effects on pain rating changes. We
      also found that the number of Met alleles at the COMT polymorphism was linearly
      correlated to the suppression of pain. In a fitted regression model, we found the
      ReHo in the ventral striatum, COMT genotype, and Openness scores accounted for
      59% of the variance in the change in pain ratings. The model was further tested
      using a separate data set from the same study. Our findings demonstrate the
      potential of combining resting-state connectivity, genetic information, and
      personality to predict placebo effect.

PMID- 24578201
TI  - Temperature- and humidity-controlled SAXS analysis of proton-conductive ionomer
      membranes for fuel cells.
AB  - We report herein temperature- and humidity-controlled small-angle X-ray
      scattering (SAXS) analyses of proton-conductive ionomer membranes. The
      morphological changes of perfluorosulfonic acid polymers (Nafion and Aquivion)
      and sulfonated aromatic block copolymers (SPE-bl-1 and SPK-bl-1) were
      investigated and compared under conditions relevant to fuel cell operation. For
      the perfluorinated ionomer membranes, water molecules were preferentially
      incorporated into ionic clusters, resulting in phase separation and formation of
      ion channels. In contrast, for the aromatic ionomer membranes, wetting led to
      randomization of the ionic clusters. The results describe the differences in the
      proton-conducting behavior between the fluorinated and nonfluorinated ionomer
      membranes, and their dependence on the humidity. 

PMID- 24578200
TI  - Population-based surveillance for cervical cancer precursors in three central
      cancer registries, United States 2009.
AB  - PURPOSE: The USA has a well-established network of central cancer registries
      (CCRs) that collect data using standardized definitions and protocols to provide
      population-based estimates of cancer incidence. The addition of cervical cancer
      precursors in select CCR operations would facilitate future studies measuring the
      population-level impact of human papillomavirus (HPV) vaccine. To assess the
      feasibility of collecting data on cervical cancer precursors, we conducted a
      multi-site surveillance study in three state-wide CCRs, to obtain annual case
      counts and compare rates of precursor lesions to those for invasive cervical
      cancer. METHODS: We developed standardized methods for case identification, data
      collection and transmission, training and quality assurance, while allowing for
      registry-specific strategies to accomplish surveillance objectives. We then
      conducted population-based surveillance for precancerous cervical lesions in
      three states using the protocols. RESULTS: We identified 5,718 cases of cervical
      cancer precursors during 2009. Age-adjusted incidence of cervical cancer
      precursors was 77 (Kentucky), 60 (Michigan), and 54 (Louisiana) per 100,000
      women. Highest rates were observed in those aged 20-29 years: 274 (Kentucky), 202
      (Michigan), and 196 (Louisiana) per 100,000. The variable with the most missing
      data was race/ethnicity, which was missing for 13 % of cases in Kentucky, 18 % in
      Michigan, and 1 % in Louisiana. Overall rates of cervical cancer precursors were
      over sixfold higher than invasive cervical cancer rates [rate ratios: 8.6
      (Kentucky), 8.3 (Michigan), and 6.2 (Louisiana)]. CONCLUSIONS: Incorporating
      surveillance of cervical cancer precursors using existing CCR infrastructure is
      feasible and results in collection of population-based incidence data.
      Standardized collection of these data in high-quality registry systems will be
      useful in future activities monitoring the impact of HPV vaccination across
      states. As a result of this study, ongoing surveillance of these lesions has now
      been conducted in four CCRs since 2010.

PMID- 24578202
TI  - Delta mean neutrophil volume (DeltaMNV) is comparable to procalcitonin for
      predicting postsurgical bacterial infection.
AB  - BACKGROUND: The Coulter LH750 (Beckman Coulter, Brea, CA) analyzer can determine
      intrinsic biophysical properties of white blood cell (WBC), known as cell
      population data. Previous studies have shown that mean neutrophil volume (MNV)
      was significantly increased in postsurgical patients with bacterial infection. To
      further validate its potential clinical usefulness, we investigate the changes in
      MNV before and after surgery, called DeltaMNV. We also compare the DeltaMNV with
      procalcitonin (PCT) and C-reactive protein (CRP) in terms of diagnostic
      sensitivity and specificity for postsurgical bacterial infection. METHODS: Blood
      samples from 300 healthy controls, 219 cardiac surgical patients without
      postsurgical infection, and 31 cardiac surgical patients complicated with
      postsurgical bacterial infection were studied. RESULTS: There are no
      statistically significant differences for WBC count and neutrophil percentage
      prior to or after surgery between postsurgical noninfected and infected patients.
      However, the DeltaMNV is significantly increased in postsurgical infected
      patients when compared with noninfected patients (P < 0.05). The receiver
      operating characteristics analysis reveals the DeltaMNV and PCT have largest
      areas under curves (0.92, 0.93 on the second day and 0.94, 0.99 on the third day
      postsurgery, respectively) compared to other parameters. CONCLUSION: DeltaMNV
      shows comparable sensitivity and specificity to PCT and superior sensitivity and
      specificity to WBC or CRP for predicting postsurgical bacterial infection. The
      potential clinical application of this parameter merits further exploration in a
      larger prospective study.

PMID- 24578204
TI  - Scanning electron microscope image signal-to-noise ratio monitoring for micro
      nanomanipulation.
AB  - As an imaging system, scanning electron microscope (SEM) performs an important
      role in autonomous micro-nanomanipulation applications. When it comes to the sub
      micrometer range and at high scanning speeds, the images produced by the SEM are
      noisy and need to be evaluated or corrected beforehand. In this article, the
      quality of images produced by a tungsten gun SEM has been evaluated by
      quantifying the level of image signal-to-noise ratio (SNR). In order to determine
      the SNR, an efficient and online monitoring method is developed based on the
      nonlinear filtering using a single image. Using this method, the quality of
      images produced by a tungsten gun SEM is monitored at different experimental
      conditions. The derived results demonstrate the developed method's efficiency in
      SNR quantification and illustrate the imaging quality evolution in SEM.

PMID- 24578205
TI  - Prime time for dissecting the entity of cryptogenic stroke.

PMID- 24578203
TI  - New approaches to management of multiple myeloma.
AB  - Multiple myeloma is still an incurable disease with pattern of regression and
      remission followed by multiple relapses raising from the residual myeloma cells
      surviving even in the patients who achieve complete clinical response to
      treatment. New antimyeloma drugs such as thalidomide, lenalidomide, and
      bortezomib have dramatically changed treatment paradigm leading to both tumor
      reduction and tumor suppression. Much progress has been made, but still many
      unsolved questions remain. In the mode of sequencing treatment for patients with
      multiple myeloma, we are still using old drugs such as the alkylating agent
      melphalan, which continues to play a central role in the transplantation setting.
      Newer drugs are now emerging and are being tested: monoclonal antibodies, histone
      deacetylase (romidespsin), MLN9708 (ixazomib) a new oral proteasome inhibitor,
      carfilzomib, signal transduction modulator perifosine. Many advances have been
      made, but there is still a long way to go.

PMID- 24578206
TI  - Evaluation of cryptogenic stroke with advanced diagnostic techniques.

PMID- 24578207
TI  - Genome-wide genotyping demonstrates a polygenic risk score associated with white
      matter hyperintensity volume in CADASIL.
AB  - BACKGROUND AND PURPOSE: White matter hyperintensities (WMH) on MRI are a
      quantitative marker for sporadic cerebral small vessel disease and are highly
      heritable. To date, large-scale genetic studies have identified only a single
      locus influencing WMH burden. This might in part relate to biological
      heterogeneity of sporadic WMH. The current study searched for genetic modifiers
      of WMH volume in cerebral autosomal-dominant arteriopathy with subcortical
      infarcts and leukoencephalopathy (CADASIL), a monogenic small vessel disease.
      METHODS: We performed a genome-wide association study to identify quantitative
      trait loci for WMH volume by combining data from 517 CADASIL patients collected
      through 7 centers across Europe. WMH volumes were centrally analyzed and
      quantified on fluid attenuated inversion recovery images. Genotyping was
      performed using the Affymetrix 6.0 platform. Individuals were assigned to 2
      distinct genetic clusters (cluster 1 and cluster 2) based on their genetic
      background. RESULTS: Four hundred sixty-six patients entered the final genome
      wide association study analysis. The phenotypic variance of WMH burden in CADASIL
      explained by all single nucleotide polymorphisms in cluster 1 was 0.85 (SE=0.21),
      suggesting a substantial genetic contribution. Using cluster 1 as derivation and
      cluster 2 as a validation sample, a polygenic score was significantly associated
      with WMH burden (P=0.001) after correction for age, sex, and vascular risk
      factors. No single nucleotide polymorphism reached genome-wide significance.
      CONCLUSIONS: We found a polygenic score to be associated with WMH volume in
      CADASIL subjects. Our findings suggest that multiple variants with small effects
      influence WMH burden in CADASIL. The identification of these variants and the
      biological pathways involved will provide insights into the pathophysiology of
      white matter disease in CADASIL and possibly small vessel disease in general.

PMID- 24578210
TI  - Poor long-term functional outcome after stroke among adults aged 18 to 50 years:
      Follow-Up of Transient Ischemic Attack and Stroke Patients and Unelucidated Risk
      Factor Evaluation (FUTURE) study.
AB  - BACKGROUND AND PURPOSE: Stroke in young adults has a dramatic effect on life;
      therefore, we investigated the long-term functional outcome after transient
      ischemic attack, ischemic stroke, or intracerebral hemorrhage in adults aged 18
      to 50 years. METHODS: We studied 722 young patients with first-ever stroke
      admitted between January 1, 1980, and November 1, 2010. Functional outcome was
      assessed by stroke subtype with the modified Rankin Scale and Instrumental
      Activities of Daily Living scale. RESULTS: After a mean follow-up of 9.1 (SD,
      8.2) years, 32.0% of all patients had a poor functional outcome (modified Rankin
      Scale, >2); for ischemic stroke, this was 36.5%, for intracerebral hemorrhage
      49.3%, and for transient ischemic attack 16.8%. At follow-up, 10.8% of transient
      ischemic attack, 14.6% of ischemic stroke, and 18.2% of intracerebral hemorrhage
      patients had a poor outcome as assessed by Instrumental Activities of Daily
      Living (<8). CONCLUSIONS: Ten years after ischemic stroke or intracerebral
      hemorrhage in young adults, 1 of 8 survivors is still dependent in daily life.

PMID- 24578209
TI  - Low socioeconomic status over 12 years and subclinical cardiovascular disease:
      the study of women's health across the nation.
AB  - BACKGROUND AND PURPOSE: The inverse relation between socioeconomic status and
      cardiovascular disease is well established. However, few studies have
      investigated socioeconomic status assessed repeatedly during adulthood in
      relation to subclinical atherosclerosis. We aimed to test whether consistently
      low socioeconomic status, as indexed by education, income, and financial strain,
      for 12 years of midlife was related to later carotid intima-media thickness and
      plaque among women. METHODS: The Study of Women's Health Across the Nation is a
      multisite longitudinal study of midlife women. Education was assessed at the
      study baseline, income and financial strain were obtained yearly for 12 years,
      and a carotid ultrasound was obtained at study year 12 among 1402 women.
      Associations were tested in linear and multinomial logistic regression models
      adjusted for demographic, biological, and behavioral risk factors. RESULTS: A
      high school education or less (odds ratio [OR] [95% confidence interval {CI}],
      1.72 [1.15-2.59]; P<0.01), some college education (OR [95% CI], 1.65 [1.17-2.32];
      P<0.01), consistently low income (OR [95% CI], 1.83 [1.15-2.89]; P<0.05), and
      consistent financial strain (OR [95% CI], 1.78 [1.21-2.61]; P<0.01) for 12 years
      were associated with higher carotid plaque, and consistent financial strain was
      associated with elevated maximal intima-media thickness (beta [SE]=0.02 [0.01];
      P<0.05) controlling for standard cardiovascular disease risk factors. When
      socioeconomic status indices were considered together, financial strain (beta
      [SE]=0.02 [0.01]; P<0.05) and low education (high school education or less: OR
      [95% CI], 1.55 [1.01-2.37]; P<0.05; some college: OR [95% CI], 1.56 [1.09-2.21];
      P<0.05) were most consistently associated with intima-media thickness and plaque,
      respectively, controlling for risk factors. CONCLUSIONS: The findings indicate
      the importance of targeting economically disadvantaged women in efforts to
      prevent cardiovascular disease among women.

PMID- 24578211
TI  - Socioeconomic status and subclinical atherosclerosis: are we closing disparity
      gaps?

PMID- 24578212
TI  - Design of multidimensional Shinnar-Le Roux radiofrequency pulses.
AB  - PURPOSE: To generalize the conventional Shinnar-Le Roux method for the design of
      multidimensional radiofrequency pulses. METHODS: Using echo-planar gradients, the
      multidimensional radiofrequency pulse design problem was converted into a series
      of one-dimensional polynomial design problems. Each of the one-dimensional
      polynomial design problems was solved efficiently. B0 inhomogeneity compensation
      and design of spatial-spectral pulses were also considered. RESULTS: The proposed
      method was used to design two-dimensional excitation and refocusing pulses. The
      results were validated through Bloch equation simulation and experiments on a 3.0
      T scanner. Large-tip-angle, equiripple-error, multidimensional excitation was
      achieved with ripple levels closely matching the design specifications.
      CONCLUSION: The conventional Shinnar-Le Roux method can be extended to design
      multidimensional radiofrequency pulses. The proposed method achieves almost
      equiripple excitation errors, allows easy control of the tradeoff among design
      parameters, and is computationally efficient.

PMID- 24578214
TI  - Inhibition of spermidine/spermine N1-acetyltransferase activity: a new
      therapeutic concept in rheumatoid arthritis.
AB  - OBJECTIVE: Changes in polyamine-modulated factor 1 (PMF-1) promoter methylation
      might favor the expression of spermidine/spermine N1-acetyltransferase 1 (SSAT
      1), causing excessive consumption of S-adenosyl methionine (SAM). This study was
      undertaken to evaluate the effect of SSAT-1 activity inhibition, either alone or
      in combination with SAM. METHODS: Synovial fibroblasts were isolated from
      patients with rheumatoid arthritis (RA) or osteoarthritis (OA). PMF-1 promoter
      methylation was determined by pyrosequencing. Small interfering RNAs (siRNAs)
      against SSAT-1 were transfected weekly in RA synovial fibroblasts (RASFs). In
      addition, synovial fibroblasts were treated with diminazene aceturate (DA), an
      inhibitor of SSAT-1. SSAT-1, 5-methylcytosine (5-MeC), adenosyl methionine
      decarboxylase (AMD), PMF-1, DNA methyltransferase 1 (DNMT-1), CXCL12, beta1
      integrin, and CD44 levels were measured by flow cytometry. Putrescine levels were
      determined by colorimetry. Levels of matrix metalloproteinases were measured by
      enzyme-linked immunosorbent assay. Cell adhesion was tested. The SCID mouse model
      of RA was used to monitor the invasiveness of RASFs. RESULTS: RASFs showed
      elevated SSAT-1, AMD, and PMF-1 levels. However, PMF-1 promoter methylation was
      unchanged. Transfection of siRNA targeting SSAT-1 increased 5-MeC levels within
      21 days. Similarly, DA increased 5-MeC levels in RASFs. In addition, DA increased
      the levels of DNMT-1, decreased the levels of AMD, putrescine, activation
      markers, and MMP-1, and altered the adhesion of RASFs. DA was more efficient in
      RASFs with higher levels of SSAT-1. Most interestingly, the combination of DA and
      SAM reduced the invasiveness of RASFs by 70%. CONCLUSION: The use of DA alone or
      in combination with SAM/L-methionine might introduce a new therapeutic concept in
      RA. This is the first therapy that would directly target RASFs and thereby
      inhibit ongoing joint destruction.

PMID- 24578213
TI  - Targeting angiogenesis in squamous non-small cell lung cancer.
AB  - Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, and
      can be further classified as nonsquamous carcinoma (including adenocarcinoma,
      which accounts for 40 % of NSCLCs) and squamous NSCLC, which makes up 30 % of
      NSCLC cases. The emergence of inhibitors of epidermal growth factor receptors,
      anaplastic lymphoma kinase, and vascular endothelial growth factors (VEGF) in the
      last decade has resulted in steady improvement in clinical outcomes for patients
      with advanced lung adenocarcinoma. However, improvements in the survival of
      patients with squamous NSCLC have remained elusive, presenting an urgent need for
      understanding and investigating therapeutically relevant molecular targets,
      specifically in squamous NSCLC. Although anti-VEGF therapy has been studied in
      squamous NSCLC, progress has been slow, in part due to issues related to
      pulmonary hemorrhage. In addition to these safety concerns, several phase III
      trials that initially included patients with squamous NSCLC failed to demonstrate
      improved overall survival (primary endpoint) with the addition of antiangiogenic
      therapy to chemotherapy compared with chemotherapy alone. Angiogenesis is an
      established hallmark of tumor progression and metastasis, and the role of VEGF
      signaling in angiogenesis is well established. However, some studies suggest
      that, while inhibiting VEGF signaling may be beneficial, prolonged exposure to
      VEGF/VEGF receptor (VEGFR) inhibitors may allow tumor cells to utilize
      alternative angiogenic mechanisms and become resistant. As a result, agents that
      target multiple angiogenic pathways simultaneously are also under evaluation.
      This review focuses on current and investigational antiangiogenic targets in
      squamous NSCLC, including VEGF/VEGFRs, fibroblast growth factor receptors,
      platelet-derived growth factor receptors, and angiopoietin. Additionally,
      clinical trials investigating VEGF- and multi-targeted antiangiogenic therapies
      are discussed. 

PMID- 24578217
TI  - Common congress swiss society of pediatrics and swiss society of infectiology :
      forum fribourg, Switzerland, june 20-22, 2002.

PMID- 24578215
TI  - A priori prediction of tumor payload concentrations: preclinical case study with
      an auristatin-based anti-5T4 antibody-drug conjugate.
AB  - The objectives of this investigation were as follows: (a) to validate a mechanism
      based pharmacokinetic (PK) model of ADC for its ability to a priori predict tumor
      concentrations of ADC and released payload, using anti-5T4 ADC A1mcMMAF, and (b)
      to analyze the PK model to find out main pathways and parameters model outputs
      are most sensitive to. Experiential data containing biomeasures, and plasma and
      tumor concentrations of ADC and payload, following A1mcMMAF administration in two
      different xenografts, were used to build and validate the model. The model
      performed reasonably well in terms of a priori predicting tumor exposure of total
      antibody, ADC, and released payload, and the exposure of released payload in
      plasma. Model predictions were within two fold of the observed exposures. Pathway
      analysis and local sensitivity analysis were conducted to investigate main
      pathways and set of parameters the model outputs are most sensitive to. It was
      discovered that payload dissociation from ADC and tumor size were important
      determinants of plasma and tumor payload exposure. It was also found that the
      sensitivity of the model output to certain parameters is dose-dependent,
      suggesting caution before generalizing the results from the sensitivity analysis.
      Model analysis also revealed the importance of understanding and quantifying the
      processes responsible for ADC and payload disposition within tumor cell, as tumor
      concentrations were sensitive to these parameters. Proposed ADC PK model provides
      a useful tool for a priori predicting tumor payload concentrations of novel ADCs
      preclinically, and possibly translating them to the clinic. 

PMID- 24578216
TI  - Effects of manganese deficiency on chondrocyte development in tibia growth plate
      of Arbor Acres chicks.
AB  - The aim of this study was to investigate the effects of manganese (Mn) deficiency
      on chondrocyte development in tibia growth plate. Ninety 1-day-old Arbor Acres
      chicks were randomly divided into three groups and fed on control diet (60 mg
      Mn/kg diet) and manganese deficient diets (40 mg Mn/kg diet, manganese deficiency
      group I; 8.7 mg Mn/kg diet, manganese deficiency group II), respectively. The
      width of the proliferative zone of growth plate was measured by the microscope
      graticule. Chondrocyte apoptosis was estimated by TUNEL staining. Gene expression
      of p21 and Bcl-2, and expression of related proteins were analyzed by
      quantitative real time reverse transcription polymerase chain reaction and
      immunohistochemistry, respectively. Compared with the control group, manganese
      deficiency significantly decreased the proliferative zone width and Bcl-2 mRNA
      expression level, while significantly increased the apoptotic rates and the
      expression level of p21 gene in chondrocytes. The results indicate that manganese
      deficiency had a negative effect on chondrocyte development, which was mediated
      by the inhibition of chondrocyte proliferation and promotion of chondrocyte
      apoptosis. 

PMID- 24578218
TI  - Preparation and characterization of electrospun curcumin loaded poly(2
      hydroxyethyl methacrylate) nanofiber--a biomaterial for multidrug resistant
      organisms.
AB  - Curcumin loaded poly(2-hydroxy ethyl methacrylate) p(HEMA) nanofiber were
      produced using electrospinning method and characterized. The nanofibrous scaffold
      supports good cell growth, attachment and retains its original morphology.
      Sustained and controlled release pattern of curcumin seen to be efficient against
      infectious disease caused by multidrug resistant organisms. Antibacterial
      activity of curcumin against Methicillin resistant staphylococcus aureus (MRSA)
      and extended spectrum beta lactamase (ESBL) proved to be a good alternate herbal
      compound for antibiotics. Hence the results indicate p(HEMA) nanofiber loaded
      with curcumin have potential to use as patch in wound healing of infectious
      disease caused by multidrug resistant organisms and excellent drug delivery
      vessel.

PMID- 24578220
TI  - A study of hepcidin and monocyte chemoattractant protein-1 in Egyptian females
      with systemic lupus erythematosus.
AB  - BACKGROUND: Lupus nephritis is one of the most serious manifestations of systemic
      lupus erythematosus (SLE). Novel biomarkers are necessary to enhance the
      diagnostic accuracy, prognostic stratification, monitoring of treatment response,
      and detection of early renal flares. METHODS: Our study was conducted on 90
      participants. They were divided into three groups, group I (controls) encompassed
      30 ages and sex-matched healthy personnel. Group II included 30 non-nephritic SLE
      patients and finally group III included 30 SLE nephritic patients. Urinary
      monocyte chemoattractant protein-1 (UMCP-1) and hepcidin were evaluated by ELISA
      technique, compared and correlated in different groups, with each other and with
      other routine variables and with renal biopsy done to study group (III). RESULTS:
      Both UMCP-1 and hepcidin in group III showed significant increase compared to
      other two groups (controls and group II) (468 +/- 128, 111 +/- 12, 252 +/- 56
      pg/ml, respectively, for UMCP-1 and 40 +/- 12, 11 +/- 2, 20 +/- 5 ng/ml,
      respectively, for hepcidin, P < 0.01). Also both UMCP-1 and hepcidin in group III
      showed significant increase in diffuse proliferative subgroup compared to focal
      proliferative and mesangioproliferative subgroups (580 +/- 43, 502 +/- 46, and
      352.6 +/- 100 pg/ml, respectively, for UMCP-1 and 47.8 +/- 9.5, 41.4 +/- 6, and
      32.9 +/- 10.8 ng/ml, respectively, for urinary hepcidin, P < 0.05). CONCLUSION:
      UMCP-1 and hepcidin could be associated with the susceptibility of lupus
      nephritis.

PMID- 24578219
TI  - Dietary phosphorus restriction by a standard low-protein diet decreased serum
      fibroblast growth factor 23 levels in patients with early and advanced stage
      chronic kidney disease.
AB  - BACKGROUND: Elevated serum fibroblast growth factor 23 (FGF23) levels are
      associated with mortality, cardiovascular disease, and disease progression in
      patients with chronic kidney disease (CKD). Although recent studies demonstrated
      that FGF23 levels decreased in response to dietary restriction of phosphorus
      and/or use of phosphate binders, research on the effects of a standard low
      protein diet is lacking. METHODS: The effects of a standard low-protein diet on
      serum FGF23, intact parathyroid hormone, and 1,25-dihydroxyvitamin D levels were
      investigated in patients with early (n = 15) and advanced (n = 20) CKD. RESULTS:
      Serum FGF23 levels decreased in both groups. Changes in FGF23 levels correlated
      with changes in 24 h urinary phosphorus excretion in the advanced CKD group.
      Decreased serum intact parathyroid hormone levels were observed only in the
      advanced CKD group and increased serum 1,25-dihydroxyvitamin D levels only in the
      early CKD group. CONCLUSIONS: These findings suggest that consuming standard low
      protein diet decreased serum FGF23 levels in patients with CKD. Serum FGF23
      levels may therefore be a useful marker to monitor the effects of a low-protein
      diet in early and advanced stage CKD.

PMID- 24578221
TI  - Concise review: From greenhouse to garden: the changing soil of the hematopoietic
      stem cell microenvironment during development.
AB  - The hematopoietic system has been intensely studied for many decades. For this
      reason, it has become the best understood stem cell-derived system that serves as
      a paradigm for stem cell biology and has found numerous applications in the
      clinics. While a lot of progress has recently been made in describing the bone
      marrow components that maintain and control blood stem cell function in the
      adult, very little is currently known about the regulatory microenvironment in
      which the first adult-repopulating hematopoietic stem cells are formed during
      development. Knowledge of these processes is crucial for understanding the basic
      regulation of hematopoietic stem cell production and behavior and to allow their
      in vitro expansion and generation from embryonic stem cells or iPS cells for
      clinical and research purposes. This review summarizes the recent advances that
      have been made in defining the cellular components, as well as the soluble and
      physical factors, that are part of the niche involved in regulating hematopoietic
      stem cell generation in the embryo. The findings are compared with what is known
      about the adult bone marrow niche to find common pathways for stem cell
      regulation, but also to highlight processes uniquely required for de novo
      hematopoietic stem cell generation, as these are the conditions that will need to
      be recreated for the successful production of blood stem cells in culture.

PMID- 24578222
TI  - A longitudinal examination of the bidirectional association between sleep
      problems and social ties at university: the mediating role of emotion regulation.
AB  - Despite the growing body of research linking sleep problems and social ties,
      research investigating the direction of effects between these two constructs is
      lacking. Furthermore, there remains a dearth of research examining the mechanisms
      that may explain the association between sleep problems and social ties within a
      longitudinal design. The present 3-year longitudinal study addressed two research
      questions: (1) Is there a bidirectional association between sleep problems and
      social ties at university? and (2) Does emotion regulation mediate the
      association between sleep problems and social ties at university? Participants (N
      = 942, 71.5% female; M = 19.01 years at Time 1, SD = 0.90) were university
      students who completed annual assessments of sleep problems, social ties, and
      emotion regulation, for three consecutive years. Results of path analysis
      indicated that the bidirectional association between sleep problems and social
      ties was statistically significant (controlling for demographics, sleep-wake
      inconsistency, sleep duration, and alcohol). Analyses of indirect effects
      indicated that emotion regulation mediated this link, such that better sleep
      quality (i.e., less sleep problems) led to more effective emotion regulation,
      which, subsequently, led to more positive social ties. In addition, more positive
      social ties led to more effective emotion regulation, which, in turn, led to less
      sleep problems. The findings highlight the critical role that emotional
      regulation plays in the link between sleep problems and social ties, and
      emphasize the need for students as well as university administration to pay close
      attention to both the sleep and social environment of university students.

PMID- 24578225
TI  - Bronchoscopic finding determined outcome after chemoradiotherapy in esophageal
      cancer patients with airway invasion.
AB  - BACKGROUND: We studied whether the bronchoscopic findings could be help to
      predict outcome after chemoradiotherapy (CRT) in patients with airway invasion by
      esophageal cancer. METHOD: Between 2000 and 2010, we retrospectively investigated
      esophageal cancer patients with T4 disease due to airway invasion who had
      received CRT as first line treatment. Airway invasion is defined as infiltration
      of the tracheobronchial wall or protruded intraluminal growth on bronchoscopy.
      The total radiation dose of CRT was 60 Gy and divided into two cycles.
      Bronchoscopic findings were evaluated together with other clinical parameters and
      correlated with overall survival (OS). RESULT: There were 68 patients with a mean
      age of 54.5 years. After the first cycle of CRT, bronchoscopic examination showed
      complete regression of endobronchial lesion in 16 patients. OS was 26% at 1 year
      and 5% at 3 years with the median survival time (MST) of 7 months. Multivariate
      analysis revealed vocal cord palsy (unfavorable, OR [95% CI]:2 [1.07-3.84], P =
      0.03), carina involvement (unfavorable, OR [95% CI]:2.6 [1.12-6], P = 0.025) and
      intraluminal tumor growth (unfavorable, OR [95% CI]:1.9 [1.1-3.3], P = 0.023) as
      independent factors for survival. The MST after CRT was 12.1, 6.1, 5.7 months in
      patients with 0, 1, 2 factors, respectively (P < 0.001). CONCLUSION:
      Bronchoscopic finding determined outcome after CRT in esophageal cancer patients
      with airway invasion.

PMID- 24578227
TI  - "Roid-Rage" at the cellular level: abolition of endogenous cardioprotection by
      anabolic steroids reveals new links between the RAAS and cardiac KATP channels :
      editorial to: "AT1 and aldosterone receptors blockade prevents the chronic effect
      of nandrolone on the exercise-induced cardioprotection in perfused rat heart
      subjected to ischemia and reperfusion" by S.R. Marques-Neto et al.

PMID- 24578226
TI  - Competitive release leads to range expansion and rampant speciation in malagasy
      dung beetles.
AB  - Competition is often thought to promote ecological diversification and thereby to
      facilitate the coexistence of competitors during evolutionary radiations. At
      large spatial scales, species may also coexist by having allopatric
      distributions, which raises the question about the role of range expansion in the
      proliferation of species during radiations. Here, we integrate a well-sampled (50
      out of 74 species) and timed phylogeny of Nanos and Apotolamprus dung beetles
      (Canthonini) in Madagascar with data on species' geographical ranges, abundances,
      and body sizes. There is an overall decline in lineage accumulation through time
      since the colonization of northern Madagascar in the mid Miocene (24-13 Ma). A
      clade of 24 extant Nanos species (clade L) originating 6.0 Ma exhibits an
      increase in speciation rate, which is associated with a significant increase in
      body size and strikingly allopatric distributions of the species. Large body size
      typically confers a competitive advantage in dung beetles, which is here
      reflected by strong numerical dominance of clade L species in local communities.
      We suggest that the "key innovation" of large body size has allowed range
      expansion due to competitive release, which has created extensive opportunities
      for allopatric speciation and differentiation along environmental gradients. Most
      theories to explain diversification patterns in Madagascar rely on allopatric
      modes of speciation, but they fail to explain how ancestral species became
      widespread in the first place. The mechanism proposed here, involving range
      expansion following competitive release via a "key innovation", may have operated
      in other Malagasy taxa with large numbers of species with small geographic
      ranges. [biodiversity hotspot; competition; Madagascar; microendemism;
      radiation.]. 

PMID- 24578229
TI  - Validation of automatic scanning of microscope slides in recovering rare cellular
      events: application for detection of fetal cells in maternal blood.
AB  - OBJECTIVE: Detection of rare fetal cells (FCs) in the maternal circulation could
      be used for non-invasive prenatal diagnosis. Considering that FCs in maternal
      blood are present in extremely low frequency, manual scanning is cumbersome, time
      consuming, and unsuitable for clinical applications. As an alternative, we
      optimized a custom-made classifier for automatic detection of FCs. METHODS: Using
      MetaSystems' automated platform, we developed a robust detection algorithm and
      validated its efficiency on retrieval of rare XY cells in a pure population of XX
      cells. Slides were scanned for presence of predefined XY cells after fluorescence
      in situ hybridization (FISH) and primed in situ labeling (PRINS). Retrieval of
      FCs was also performed on samples from maternal blood. RESULTS: The efficiency of
      detection of rare XY cells was 88% using FISH (117/133) in comparison with 78%
      (53/68) with PRINS. FC frequencies per 1 mL of maternal blood ranged from 3 to 6
      FCs in normal pregnancies versus 13 to 21 FCs in Down syndrome pregnancies.
      CONCLUSION: Automatic scanning was more efficient and consistent than manual
      scanning for detection of rare FCs and required considerably less operator time.
      Automatic scanning using FISH is more sensitive than that using PRINS. The study
      validates automatic scanning retrieval of FCs from maternal blood.

PMID- 24578230
TI  - Effect of tooth brush abrasion and thermo-mechanical loading on direct and
      indirect veneer restorations.
AB  - OBJECTIVES: This study investigated toothbrush abrasion and in vitro aging on
      ceramic (indirect technique) and composite veneers (direct technique). MATERIALS
      AND METHODS: Identical composite and individual human incisors were restored with
      industrially preformed composite veneers, indirectly produced ceramic veneers,
      and direct composite restorations. Surface roughness was determined before and
      after tooth brushing. A 5-year period of oral service was simulated by thermal
      cycling and mechanical loading (TCML). After TCML, all specimens were examined
      with microscopy and scanning electron microscopy. Specimens without failures
      during TCML were loaded until failure. STATISTICS: analysis of variance;
      Bonferroni's post hoc analysis, Kaplan-Meier-Log Rank test (alpha = 0.05).
      RESULTS: Tooth brushing yielded a non-significant increase (p = 0.560) in
      roughness in all materials (industrial veneer, 0.12+/-0.07 MUm, direct
      restoration, 0.18+/-0.14 MUm, ceramic, 0.35+/-0.16 MUm). No significant
      differences in roughness could be determined between the materials, neither
      before nor after testing (p < 0.001). After TCML of artificial teeth, direct and
      preformed composite veneers on composite teeth showed no failures or damages. Two
      ceramic veneers showed cracking in the labial area. After TCML of human teeth,
      transmission microscopy indicated a facial crack in a ceramic veneer and chipping
      in the cervical area of a preformed veneer. Two direct composite veneers lost
      retention. No significantly different survival rates were found between the three
      veneer groups. Fracture force on human teeth varied between 527.8+/-132.4 N
      (ceramic), 478.3+/-165.4 N (preformed composite), and 605.0+/-263.5 N (direct
      composite). CONCLUSION: All materials revealed comparable wear resistance.
      Indirect ceramic, direct restorative composite, and preformed composite veneers
      showed comparable failure rates and satisfying longevity. CLINICAL RELEVANCE: The
      results indicate similar longevity of the chosen materials for veneer
      restorations.

PMID- 24578231
TI  - Effect of commercial fluoride dentifrices against hydrochloric acid in an erosion
      abrasion model.
AB  - OBJECTIVES: This study assessed the effect of three commercial dentifrices with
      different fluoride-containing compounds in controlling the progression of dentin
      loss using an in vitro erosion-abrasion model. MATERIALS AND METHODS: Dentin
      specimens were randomized into four groups (n = 10): control (no F), Elmex (1,400
      ppm AmF), Meridol (1,400 ppm AmF/SnF2), and Crest Pro-Health (1,100 ppm SnF2).
      The dentin specimens were submitted to cycles of demineralization (HCl 0.01 M for
      60 s), remineralization (artificial saliva for 60 min), and immersion in 1:3 w/w
      of dentifrice/artificial saliva, followed by toothbrushing (150 brushing
      strokes). The cycle was repeated three times daily for 5 days. Surface loss was
      quantified by stylus profilometry. Data were submitted to one-way ANOVA and
      Tukey's tests (p < 0.05). RESULTS: Wear (MUm +/- SD) was control 4.1 +/- 1.2,
      Elmex 3.7 +/- 1.5, Meridol 1.3 +/- 0.4, and Crest Pro-Health 2.1 +/- 0.7.
      Therefore, all products (except Elmex) produced statistically significantly less
      mineral loss (p < 0.05) when compared with the control. CONCLUSION: None of the
      dentifrices avoided the erosive-abrasive process; however, SnF2-containing
      dentifrices were effective in statistically significantly reducing dentin loss.
      CLINICAL RELEVANCE: Scientific literature shows evidence that fluoride can
      strengthen dental tissue against erosive acid damage. However, the beneficial
      effect of different fluorides present in commercial dentifrices is questionable.
      Thus, a determination of an effective fluoride dentifrice may be beneficial in
      the reduction of the erosive process in patients with gastric disorders.

PMID- 24578233
TI  - A new flow cytometric method for differential cell counting in ascitic fluid.
AB  - Background: Cell counts in bodyfluids such as ascitic fluid can be difficult to
      perform and report rapidly. The current gold standard for cell counting in body
      fluids is a suitable automated cell counter or a manual counting chamber,
      combined with differential counting on a cytospin. This technique has several
      disadvantages, so we designed a new flow cytometric test for cell counting in
      ascites. We compared this with an automatic cell counter (LH750, Beckman Coulter)
      and manual counting of cytospins. Methods: Ascitic samples (n=53) from 38
      patients were studied. Polymorphonuclear neutrophils (PMN), lymphocytes,
      eosinophils, and macrophages were defined by flow cytometry. We compared this
      with our reference method: the absolute cell concentration calculated from the
      leukocyte concentration of the LH750 combined with a differential cell count
      performed manually on a cytospin. Results: The outcomes of validation experiments
      (linearity, reproducibility and detection limit) of the flow cytometric assay
      prove it is well suited for cell counting in ascitic fluid. Conclusions: Based on
      analytical performance, flow cytometry is suited for cell counting in ascitic
      fluid. An ascitic fluid cell count is frequently ordered to detect spontaneous
      bacterial peritonitis (SBP). If the PMN count is >= 250 cells/mm3 , SBP is highly
      suspected. Using our reference method, we calculated the sensitivities and
      specificities to detect >= 250 PMN cells/mm3 for the LH750 (100% and 65%
      respectively) and flow cytometric assay (100 %, 100 %). As flow cytometry is
      easier and faster we recommend this method for rapid cell counting in ascitic
      fluid. (c) 2014 Clinical Cytometry Society.

PMID- 24578232
TI  - Identification of alpha2-macroglobulin as a master inhibitor of cartilage
      degrading factors that attenuates the progression of posttraumatic
      osteoarthritis.
AB  - OBJECTIVE: To determine if supplemental intraarticular alpha2-macroglobulin
      (alpha2 M) has a chondroprotective effect in a rat model of osteoarthritis (OA).
      METHODS: Using Western blotting, mass spectrometry, enzyme-linked immunosorbent
      assay (ELISA), and immunohistochemistry, alpha2 M was identified as a potential
      therapeutic agent through a comparison of alpha2 M concentrations in serum,
      synovial fluid (SF), and cartilage from normal subjects and patients with OA. In
      cultured chondrocytes, the effects of alpha2 M on interleukin-1 (IL-1)-induced
      cartilage catabolic enzymes were evaluated by Luminex assay and ELISA. In vivo
      effects on cartilage degeneration and matrix metalloproteinase 13 (MMP-13)
      concentration were evaluated in male rats (n = 120) randomized to 1 of 4
      treatments: 1) anterior cruciate ligament transection (ACLT) and saline
      injections, 2) ACLT and 1 IU/kg injections of alpha2 M, 3) ACLT and 2 IU/kg
      injections of alpha2 M, or 4) sham operation and saline injections. Rats were
      administered intraarticular injections for 6 weeks. The concentration of MMP-13
      in SF lavage fluid was measured using ELISA. OA-related gene expression was
      quantified by real-time quantitative polymerase chain reaction. The extent of OA
      progression was graded by histologic examination. RESULTS: In both normal
      subjects and OA patients, alpha2 M levels were lower in SF as compared to serum,
      and in OA patients, MMP-13 levels were higher in SF than in serum. In vitro,
      alpha2 M inhibited the induction of MMP-13 by IL-1 in a dose-dependent manner in
      human chondrocytes. In the rat model of ACLT OA, supplemental intraarticular
      injection of alpha2 M reduced the concentration of MMP-13 in SF, had a favorable
      effect on OA-related gene expression, and attenuated OA progression. CONCLUSION:
      The plasma protease inhibitor alpha2 M is not present in sufficient
      concentrations to inactivate the high concentrations of catabolic factors found
      in OA SF. Our findings suggest that supplemental intraarticular alpha2 M provides
      chondral protection in posttraumatic OA.

PMID- 24578234
TI  - Interventions for heart failure readmissions: successes and failures.
AB  - Heart failure readmissions result in significant costs to the health care system
      and to patients' quality of life, but programs to reduce readmissions have met
      with mixed success. Successful strategies have included multidisciplinary
      hospital-based quality initiatives, disease management programs, and care
      transition interventions. Devices like telemonitors and indwelling catheters,
      however, have met with mixed success. Research is still needed to elucidate the
      most effective interventions for readmission reduction in the HF population. 

PMID- 24578235
TI  - Evaluation of renal functions in preterm infants with respiratory distress
      syndrome.
AB  - BACKGROUND: The aim of this prospective study was to evaluate urinary glutathione
      S transferases pi (GST-pi), beta-2-microglobulin (B2-MG), and N-acetyl-beta-d
      glucosaminidase (NAG) levels as markers revealing the effect of respiratory
      distress syndrome (RDS) on renal function in preterm infants. METHODS: The study
      was performed with 76 preterm infants whose gestational ages were between 28 and
      32 weeks. Twenty-six preterm infants with RDS (cases) and 50 preterm infants
      without RDS (controls) enrolled in the study. Blood and urine samples were
      obtained on postnatal (PN) day 3 and 30. Urinary GST-pi levels were measured by
      enzyme-linked immunosorbent assay (ELISA), and urinary B2-MG levels were
      determined by nephelometric method. RESULTS: There was no significant difference
      in urinary B2-MG and GST-pi levels between RDS and non-RDS groups on PN day 3 (P
      > 0.05 for each). However, preterm infants with RDS had significantly higher
      urinary B2-MG and GST-pi levels than the control group on PN day 30 (P = 0.0001
      and P = 0.031, respectively). Urinary NAG levels were higher in RDS group than
      those of the controls on both PN day 3 and 30, but these findings were not
      statistically significant (P > 0.05, for each). CONCLUSION: Preterm infants with
      RDS had increased levels of both GST-pi and B2-MG levels on PN day 30, suggesting
      subclinical tubular dysfunction, probably secondary to hypoxic stress.

PMID- 24578236
TI  - Tocolytics for preterm premature rupture of membranes.
AB  - BACKGROUND: In women with preterm labor, tocolysis has not been shown to improve
      perinatal mortality; however, it is often given for 48 hours to allow for the
      corticosteroid effect for fetal maturation. In women with preterm premature
      rupture of membranes (PPROM), the use of tocolysis is still controversial. In
      theory, tocolysis may prolong pregnancy in women with PPROM, thereby allowing for
      the corticosteroid benefit and reducing the morbidity and mortality associated
      with prematurity. OBJECTIVES: To assess the potential benefits and harms of
      tocolysis in women with preterm premature rupture of membranes. SEARCH METHODS:
      We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (15
      January 2014). SELECTION CRITERIA: We included pregnant women with singleton
      pregnancies and PPROM (23 weeks to 36 weeks and six days). We included any
      tocolytic therapy compared to no tocolytic, placebo, or another tocolytic. DATA
      COLLECTION AND ANALYSIS: All review authors assessed the studies for inclusion.
      We extracted and quality assessed data. MAIN RESULTS: We included eight studies
      with a total of 408 women. Seven of the studies compared tocolysis to no
      tocolysis. One study compared nifedipine to terbutaline. Compared to no
      tocolysis, tocolysis was not associated with a significant effect on perinatal
      mortality in women with PPROM (risk ratio (RR) 1.67; 95% confidence interval (CI)
      0.85 to 3.29). Tocolysis was associated with longer latency (mean difference (MD)
      73.12 hours; 95% CI 20.21 to 126.03; three trials of 198 women) and fewer births
      within 48 hours (average RR 0.55; 95% CI 0.32 to 0.95; six trials of 354 women;
      random-effects, Tau2 = 0.18, I2 = 43%) compared to no tocolysis. However,
      tocolysis was associated with increased five-minute Apgar of less than seven (RR
      6.05; 95% CI 1.65 to 22.23; two trials of 160 women) and increased need for
      ventilation of the neonate (RR 2.46; 95% CI 1.14 to 5.34; one trial of 81 women).
      In the subgroup analysis comparing betamimetic to no betamimetics, tocolysis was
      associated with increased latency and borderline significance for
      chorioamnionitis. Prophylactic tocolysis with PPROM was associated with increased
      overall latency, without additional benefits for maternal/neonatal outcomes. For
      women with PPROM before 34 weeks, there was a significantly increased risk of
      chorioamnionitis in women who received tocolysis. However, neonatal outcomes were
      not significantly different. There were no significant differences in
      maternal/neonatal outcomes in subgroup analyses comparing cox inhibitor versus no
      tocolysis, calcium channel blocker versus betamimetic, antibiotic, corticosteroid
      or combined antibiotic/corticosteroid. AUTHORS' CONCLUSIONS: Our review suggests
      there is insufficient evidence to support tocolytic therapy for women with PPROM,
      as there was an increase in maternal chorioamnionitis without significant
      benefits to the infant. However, studies did not consistently administer latency
      antibiotics and corticosteroids, both of which are now considered standard of
      care.

PMID- 24578237
TI  - Best practices for the development, scale-up, and post-approval change control of
      IR and MR dosage forms in the current quality-by-design paradigm.
AB  - In this whitepaper, the Manufacturing Technical Committee of the Product Quality
      Research Institute provides information on the common, best practices in use
      today in the development of high-quality chemistry, manufacturing and controls
      documentation. Important topics reviewed include International Conference on
      Harmonization, in vitro-in vivo correlation considerations, quality-by-design
      approaches, process analytical technologies and current scale-up, and process
      control and validation practices. It is the hope and intent that this whitepaper
      will engender expanded dialog on this important subject by the pharmaceutical
      industry and its regulatory bodies.

PMID- 24578239
TI  - Liquid chromatography-tandem mass spectrometry enzyme assay for UDP-galactose 4'
      epimerase: use of fragment intensity ratio in differentiation of structural
      isomers.
AB  - BACKGROUND: Distinction between asymptomatic and potentially clinically
      significant forms of galactosemia due to UDP-galactose 4'-epimerase (GALE)
      deficiency requires enzyme measurement in erythrocytes and other cells. We sought
      to develop a GALE assay using a novel liquid chromatography-tandem mass
      spectrometry (LC-MS/MS)-based method. METHODS: The reversible GALE assay was
      conducted with UDPGal as a substrate. The coeluting reaction product, uridine
      diphosphate glucose (UDPGlc), and its isomeric substrate, uridine diphosphate
      galactose (UDPGal), were detected by MS/MS at mass transitions 565 > 280, 565 >
      241 and 565 > 403. The UDPGal was enriched in mass transition 565 > 403 compared
      with UDPGlc, whereas the UDPGlc was enriched in the mass transition 565 > 241
      compared with UDPGal. The percentage of UDPGal in the reaction mixture was
      calculated by use of the ratio of ion intensities of the 2 daughter ions and a
      fourth-order polynomial calibrator curve. RESULTS: The method yielded a mean (SD)
      GALE activity of 9.8 (2.2) MUmol . g(-1) hemoglobin . h(-1) in erythrocyte
      extracts from 27 controls. The apparent Km of the substrate, UDPGal, was 0.05
      mmol/L. The GALE activity ranged from 433 to 993 MUmol . g(-1) protein . h(-1) in
      control lymphoblast extracts. In a blinded test of 22 subjects suspected of GALE
      deficiency, we identified 6 individuals whose residual activities were below the
      range of controls, compatible with intermediate GALE deficiency. CONCLUSIONS:
      This assay can be used to distinguish the different forms of GALE deficiency.
      From an analytical standpoint, differentiating isomers on the basis of fragment
      intensity ratios should also prove useful for analogous enzymatic studies
      involving substrates and products that are structural isomers.

PMID- 24578238
TI  - Definitive chemoradiotherapy with capecitabine and cisplatin for elder patients
      with locally advanced squamous cell esophageal cancer.
AB  - PURPOSE: The aim of this retrospective study is to evaluate the feasibility and
      efficacy of concurrent chemoradiotherapy (CCRT) or sequential chemoradiotherapy
      (SCRT) with capecitabine and cisplatin for elderly patients with locally advanced
      esophageal squamous cell carcinoma (ESCC). METHODS: A total of 75 patients elder
      than 65 years with histologically proven stage II-III ESCC were enrolled, in whom
      40 patients were treated with CCRT consisted of two cycles of intravenous
      cisplatin and oral capecitabine during and after radiotherapy and 35 patients
      were treated with SCRT as two cycles of capecitabine plus cisplatin before and
      after radiotherapy. Response rate, overall survival, progression-free survival
      and toxicity were compared. RESULTS: The overall response rate (CR + PR) in the
      CCRT group (91.6 %) was significantly higher than that in the SCRT group (67.7
      %), P = 0.023. The median PFS and median OS were significantly higher in CCRT
      group (19.7 and 33.6 months) than those in SCRT group (11.6 and 15.7 months), P <
      0.05. The acute toxic effect was more severe in the CCRT group than in the SCRT
      group, but the grade 3-4 acute toxicities were similar in two groups.
      CONCLUSIONS: It suggested that both CCRT and SCRT with capecitabine and cisplatin
      are tolerable and effective for elderly patients with locally advanced ESCC.
      Concurrent CRT might be superior to SCRT.

PMID- 24578240
TI  - Impact of 18F-fluoride PET in patients with known prostate cancer: initial
      results from the National Oncologic PET Registry.
AB  - Under Medicare's Coverage with Evidence Development policy, PET using (18)F
      sodium fluoride (NaF PET) to identify osseous metastasis became a covered service
      if prospective registry data were collected. The National Oncologic PET Registry
      (NOPR) developed a NaF PET registry built on the foundation of its prior registry
      for PET with (18)F-FDG. Men with prostate cancer represented 72% of the cases.
      METHODS: Prospective data before and after NaF PET were collected from referring
      and interpreting physicians. The analysis set consisted of consenting men age 65
      y or older with prostate cancer undergoing NaF PET for initial staging (IS, n =
      1,024), suspected first osseous metastasis (FOM, n = 1,997), or suspected
      progression of osseous metastasis (POM, n = 510). RESULTS: Referring physicians
      indicated that if NaF PET were not available, other advanced imaging (body CT, MR
      imaging, or (18)F-FDG PET) would be their plan in about half of the cases. After
      NaF PET, the postimaging plan was revised to treatment in 77%, 52%, and 71% for
      IS, FOM, and POM, respectively. When intended management was classified as either
      treatment or nontreatment, the overall change in intended management ranged from
      44% to 52% and from 12% to 16% if no effect was assumed for those cases with pre
      PET plans for other imaging (imaging-adjusted impact). Interpreting physicians
      recorded definite findings of bone metastasis in 14%, 29%, and 76% for IS, FOM,
      and POM, respectively. The intended care patterns varied widely across indication
      and scan abnormality category combinations. CONCLUSION: NaF PET has high overall
      impact, principally related to its effect on replacing intended use of other
      advanced imaging. Its imaging-adjusted impact was similar to that observed with
      (18)F-FDG PET for restaging or suspected recurrence in other cancer types.

PMID- 24578241
TI  - Improved tumor targeting of anti-HER2 nanobody through N-succinimidyl 4
      guanidinomethyl-3-iodobenzoate radiolabeling.
AB  - Nanobodies are approximately 15-kDa proteins based on the smallest functional
      fragments of naturally occurring heavy chain-only antibodies and represent an
      attractive platform for the development of molecularly targeted agents for cancer
      diagnosis and therapy. Because the human epidermal growth factor receptor type 2
      (HER2) is overexpressed in breast and ovarian carcinoma, as well as in other
      malignancies, HER2-specific Nanobodies may be valuable radiodiagnostics and
      therapeutics for these diseases. The aim of the present study was to evaluate the
      tumor-targeting potential of anti-HER2 5F7GGC Nanobody after radioiodination with
      the residualizing agent N-succinimidyl 4-guanidinomethyl 3-(125/131)I
      iodobenzoate (*I-SGMIB). METHODS: The 5F7GGC Nanobody was radiolabeled using *I
      SGMIB and, for comparison, with N(epsilon)-(3-*I-iodobenzoyl)-Lys(5)-N(alpha)
      maleimido-Gly(1)-GEEEK (*I-IB-Mal-d-GEEEK), another residualizing agent, and by
      direct radioiodination using IODO-GEN ((125)I-Nanobody). The 3 labeled Nanobodies
      were evaluated in affinity measurements, and paired-label internalization assays
      were performed on HER2-expressing BT474M1 breast carcinoma cells and in paired
      label tissue distribution measurements in mice bearing subcutaneous BT474M1
      xenografts. RESULTS: *I-SGMIB-Nanobody was produced in 50.4% +/- 3.6%
      radiochemical yield and exhibited a dissociation constant of 1.5 +/- 0.5 nM.
      Internalization assays demonstrated that intracellular retention of radioactivity
      was up to 1.5-fold higher for *I-SGMIB-Nanobody than for coincubated (125)I
      Nanobody or *I-IB-Mal-d-GEEEK-Nanobody. Peak tumor uptake for *I-SGMIB-Nanobody
      was 24.50% +/- 9.89% injected dose/g at 2 h, 2- to 4-fold higher than observed
      with other labeling methods, and was reduced by 90% with trastuzumab blocking,
      confirming the HER2 specificity of localization. Moreover, normal-organ clearance
      was fastest for *I-SGMIB-Nanobody, such that tumor-to-normal-organ ratios greater
      than 50:1 were reached by 24 h in all tissues except lungs and kidneys, for which
      the values were 10.4 +/- 4.5 and 5.2 +/- 1.5, respectively. CONCLUSION: Labeling
      anti-HER2 Nanobody 5F7GGC with *I-SGMIB yields a promising new conjugate for
      targeting HER2-expressing malignancies. Further research is needed to determine
      the potential utility of *I-SGMIB-5F7GGC labeled with (124)I, (123)I, and (131)I
      for PET and SPECT imaging and for targeted radiotherapy, respectively.

PMID- 24578242
TI  - Functional imaging of oxidative stress with a novel PET imaging agent, 18F-5
      fluoro-L-aminosuberic acid.
AB  - Glutathione is the predominant endogenous cellular antioxidant, playing a
      critical role in the cellular defensive response to oxidative stress by
      neutralizing free radicals and reactive oxygen species. With cysteine as the rate
      limiting substrate in glutathione biosynthesis, the cystine/glutamate transporter
      (system xc(-)) represents a potentially attractive PET biomarker to enable in
      vivo quantification of xc(-) activity in response to oxidative stress associated
      with disease. We have developed a system xc(-) substrate that incorporates
      characteristics of both natural substrates, L-cystine and L-glutamate (L-Glu). L
      aminosuberic acid (L-ASu) has been identified as a more efficient system xc(-)
      substrate than L-Glu, leading to an assessment of a series of anionic amino acids
      as prospective PET tracers. Herein, we report the synthesis and in vitro and in
      vivo validation of a lead candidate, (18)F-5-fluoro-aminosuberic acid ((18)F
      FASu), as a PET tracer for functional imaging of a cellular response to oxidative
      stress with remarkable tumor uptake and retention. METHODS: (18)F-FASu was
      identified as a potential PET tracer based on an in vitro screening of compounds
      similar to L-cystine and L-Glu. Affinity toward system xc(-) was determined via
      in vitro uptake and inhibition studies using oxidative stress-induced EL4 and
      SKOV-3 cells. In vivo biodistribution and PET imaging studies were performed in
      mice bearing xenograft tumors (EL4 and SKOV-3). RESULTS: In vitro assay results
      determined that L-ASu inhibited system xc(-) as well as or better than L-Glu. The
      direct comparison of uptake of tritiated compounds demonstrated more efficient
      system xc(-) uptake of L-ASu than L-Glu. Radiosynthesis of (18)F-FASu allowed the
      validation of uptake for the fluorine-bearing derivative in vitro. Evaluation in
      vivo demonstrated primarily renal clearance and uptake of approximately 8
      percentage injected dose per gram in SKOV-3 tumors, with tumor-to-blood and tumor
      to-muscle ratios of approximately 12 and approximately 28, respectively. (18)F
      FASu uptake was approximately 5 times greater than (18)F-FDG uptake in SKOV-3
      tumors. Dynamic PET imaging demonstrated uptake in EL4 tumor xenografts of
      approximately 6 percentage injected dose per gram and good tumor retention for at
      least 2 h after injection. CONCLUSION: (18)F-FASu is a potentially useful
      metabolic tracer for PET imaging of a functional cellular response to oxidative
      stress. (18)F-FASu may provide more sensitive detection than (18)F-FDG in certain
      tumors.

PMID- 24578244
TI  - Concise review: the surface markers and identity of human mesenchymal stem cells.
AB  - The concept of mesenchymal stem cells (MSCs) is becoming increasingly obscure due
      to the recent findings of heterogeneous populations with different levels of
      stemness within MSCs isolated by traditional plastic adherence. MSCs were
      originally identified in bone marrow and later detected in many other tissues.
      Currently, no cloning based on single surface marker is capable of isolating
      cells that satisfy the minimal criteria of MSCs from various tissue environments.
      Markers that associate with the stemness of MSCs await to be elucidated. A number
      of candidate MSC surface markers or markers possibly related to their stemness
      have been brought forward so far, including Stro-1, SSEA-4, CD271, and CD146, yet
      there is a large difference in their expression in various sources of MSCs. The
      exact identity of MSCs in vivo is not yet clear, although reports have suggested
      they may have a fibroblastic or pericytic origin. In this review, we revisit the
      reported expression of surface molecules in MSCs from various sources, aiming to
      assess their potential as MSC markers and define the critical panel for future
      investigation. We also discuss the relationship of MSCs to fibroblasts and
      pericytes in an attempt to shed light on their identity in vivo.

PMID- 24578243
TI  - Comparison of 18F-FET PET and perfusion-weighted MR imaging: a PET/MR imaging
      hybrid study in patients with brain tumors.
AB  - PET using O-(2-(18)F-fluoroethyl)-L-tyrosine ((18)F-FET) provides important
      diagnostic information in addition to that from conventional MR imaging on tumor
      extent and activity of cerebral gliomas. Recent studies suggest that perfusion
      weighted MR imaging (PWI), especially maps of regional cerebral blood volume
      (rCBV), may provide similar diagnostic information. In this study, we directly
      compared (18)F-FET PET and PWI in patients with brain tumors. METHODS: Fifty-six
      patients with gliomas were investigated using static (18)F-FET PET and PWI. For
      comparison, 8 patients with meningiomas were included. We generated a set of
      tumor and reference volumes of interest (VOIs) based on morphologic MR imaging
      and transferred these VOIs to the corresponding (18)F-FET PET scans and PWI maps.
      From these VOIs, tumor-to-brain ratios (TBR) were calculated, and normalized
      histograms were generated for (18)F-FET PET and rCBV maps. Furthermore, in rCBV
      maps and in (18)F-FET PET scans, tumor volumes, their spatial congruence, and the
      distance between the local hot spots were assessed. RESULTS: For patients with
      glioma, TBR was significantly higher in (18)F-FET PET than in rCBV maps (TBR,
      2.28 +/- 0.99 vs. 1.62 +/- 1.13; P < 0.001). Histogram analysis of the VOIs
      revealed that (18)F-FET scans could clearly separate tumor from background. In
      contrast, deriving this information from rCBV maps was difficult. Tumor volumes
      were significantly larger in (18)F-FET PET than in rCBV maps (tumor volume, 24.3
      +/- 26.5 cm(3) vs. 8.9 +/- 13.9 cm(3); P < 0.001). Accordingly, spatial overlap
      of both imaging parameters was poor (congruence, 11.0%), and mean distance
      between the local hot spots was 25.4 +/- 16.1 mm. In meningioma patients, TBR was
      higher in rCBV maps than in (18)F-FET PET (TBR, 5.33 +/- 2.63 vs. 2.37 +/- 0.32;
      P < 0.001) whereas tumor volumes were comparable. CONCLUSION: In patients with
      cerebral glioma, tumor imaging with (18)F-FET PET and rCBV yields different
      information. (18)F-FET PET shows considerably higher TBRs and larger tumor
      volumes than rCBV maps. The spatial congruence of both parameters is poor. The
      locations of the local hot spots differ considerably. Taken together, our data
      show that metabolically active tumor tissue of gliomas as depicted by amino acid
      PET is not reflected by rCBV as measured with PWI.

PMID- 24578245
TI  - Dry polymerization of 3',5'-cyclic GMP to long strands of RNA.
AB  - Recent progress in the synthesis of nucleotides from prebiotically plausible
      precursors has opened up new ways to explain the origin of genetic matter.
      Mechanisms for the polymerization of nucleotides without the help of catalysts
      are, however, rare. Complementary to the experiments done by Costanzo et al., we
      found that drying 3',5'-cyclic GMP leads to poly-G RNA strands with lengths of up
      to 40 nucleotides. We also show that the polymerization to long RNA strands is
      considerably more efficient under dry conditions than for cGMP polymerization in
      water. The length depends on the incubation time of dry nucleotides at
      temperatures of 40-80  degrees C. No enzymes or other catalysts are needed for
      successful polymerization. 

PMID- 24578246
TI  - Hilar cholangiocarcinoma: no longer hopeless.

PMID- 24578247
TI  - Stability of [-2]Pro-PSA in whole blood and serum: analysis for optimal
      measurement conditions.
AB  - BACKGROUND: The clinical usefulness of [-2]pro-PSA (where PSA is prostate
      specific antigen) in prostate cancer diagnosis has been emphasized in recent
      studies. To determine proper blood sample handling conditions for [-2]pro-PSA
      evaluation, we analyzed the preanalytical stability of [-2]pro-PSA. METHODS:
      Blood samples from 22 Japanese males were stored under various conditions before
      total PSA (tPSA), free PSA, and [-2]pro-PSA concentrations were measured, and the
      preanalytical stability of [-2]pro-PSA and the changes in the Prostate Health
      Index (phi) were assessed. RESULTS: [-2]Pro-PSA was stable in serum for at least
      24 hr at both room temperature (RT) and at 4 degrees C. However, [-2]pro-PSA
      levels in whole blood increased rapidly over time, particularly at RT. Mean
      recovery (%) of [-2]pro-PSA in whole blood at RT was >110% at 1 hr after drawing
      of blood. The phi tended to increase over time in a pattern similar to the change
      in[-2]pro-PSA. CONCLUSIONS: Preanalytical stability was lower for [-2]pro-PSA
      than for free PSA or tPSA. Whole-blood [-2]pro-PSA increased in a time-dependent
      manner, particularly at RT. Thus, whole blood samples collected at RT should be
      centrifuged within 1 hr after drawing. The [-2]pro-PSA in serum is stable for at
      least 24 hr at both RT and at 4 degrees C.

PMID- 24578248
TI  - Resection versus other treatments for locally advanced pancreatic cancer.
AB  - BACKGROUND: Pancreatic cancer is an aggressive cancer. Resection of the cancer is
      the only treatment with the potential to achieve long-term survival. However, a
      third of patients with pancreatic cancer have locally advanced cancer involving
      adjacent structures such as blood vessels which are not usually removed because
      of fear of increased complications after surgery. Such patients often receive
      palliative treatment. Resection of the pancreas along with the involved vessels
      is an alternative to palliative treatment for patients with locally advanced
      pancreatic cancer. OBJECTIVES: To compare the benefits and harms of surgical
      resection versus palliative treatment in patients with locally advanced
      pancreatic cancer. SEARCH METHODS: We searched the Cochrane Central Register of
      Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 12), MEDLINE,
      EMBASE, Science Citation Index Expanded, and trial registers until February 2014.
      SELECTION CRITERIA: We included randomised controlled trials comparing pancreatic
      resection versus palliative treatments for patients with locally advanced
      pancreatic cancer (irrespective of language or publication status). DATA
      COLLECTION AND ANALYSIS: Two authors independently assessed trials for inclusion
      and independently extracted the data. We analysed the data with both the fixed
      effect and random-effects models using Review Manager (RevMan). We calculated the
      hazard ratio (HR), risk ratio (RR) or mean difference (MD) with 95% confidence
      intervals (CI) based on an intention-to-treat analysis. MAIN RESULTS: We
      identified two trials comparing pancreatic resection versus other treatments for
      patients with locally advanced pancreatic cancer. Ninety eight patients were
      randomised to pancreatic resection (n = 47) or palliative treatment (n = 51) in
      the two trials included in this review. Both trials were at high risk of bias.
      Both trials included patients who had locally advanced pancreatic cancer which
      involved the serosa anteriorly or retroperitoneum posteriorly or involved the
      blood vessels. Such pancreatic cancers would be considered generally
      unresectable. One trial included patients with pancreatic cancer in different
      locations of the pancreas including the head, neck and body (n = 42). The
      patients allocated to the pancreatic resection group underwent partial pancreatic
      resection (pancreatoduodenectomy with lymph node clearance or distal pancreatic
      resection with lymph node clearance) in this trial; the control group received
      palliative treatment with chemoradiotherapy. In the other trial, only patients
      with cancer in the head or neck of the pancreas were included (n = 56). The
      patients allocated to the pancreatic resection group underwent en bloc total
      pancreatectomy with splenectomy and vascular reconstruction in this trial; the
      control group underwent palliative bypass surgery with chemoimmunotherapy. The
      pancreatic resection group had lower mortality than the palliative treatment
      group (HR 0.38; 95% CI 0.25 to 0.58, very low quality evidence). Both trials
      followed the survivors up to at least five years. There were no survivors at two
      years in the palliative treatment group in either trial. Approximately 40% of the
      patients who underwent pancreatic resection were alive in the pancreatic
      resection group at the end of three years. This difference in survival was
      statistically significant (RR 22.68; 95% CI 3.15 to 163.22). The difference
      persisted at five years of follow-up (RR 8.65; 95% CI 1.12 to 66.89). Neither
      trial reported severe adverse events but it is likely that a significant
      proportion of patients suffered from severe adverse events in both groups. The
      overall peri-operative mortality in the resection group in the two trials was
      2.5%. None of the trials reported quality of life. The estimated difference in
      the length of total hospital stay (which included all admissions of the patient
      related to the treatment) between the two groups was imprecise (MD -23.00 days;
      95% CI -59.05 to 13.05, very low quality evidence). The total treatment costs
      were significantly lower in the pancreatic resection group than the palliative
      treatment group (MD -10.70 thousand USD; 95% CI -14.11 to -7.29, very low quality
      evidence). AUTHORS' CONCLUSIONS: There is very low quality evidence that
      pancreatic resection increases survival and decreases costs compared to
      palliative treatments for selected patients with locally advanced pancreatic
      cancer and venous involvement. When sufficient expertise is available, pancreatic
      resection could be considered for selected patients with locally advanced
      pancreatic cancer who are willing to accept the potentially increased morbidity
      associated with the procedure. Further randomised controlled trials are necessary
      to increase confidence in the estimate of effect and to assess the quality of
      life of patients and the cost-effectiveness of pancreatic resection versus
      palliative treatment for locally advanced pancreatic cancer.

PMID- 24578250
TI  - Definitions and the experience of fertility problems: infertile and sub-fertile
      women, childless mothers, and honorary mothers in two southern Nigerian
      communities.
AB  - Although infertility causes women considerable grief, social stigma, and economic
      deprivation, scholars have paid little attention to infertility's definitions
      that may depart from the standard Western usage and how such definitions
      influence the way women experience the condition. This article, by listening to
      individual women's experiences of infertility in two Nigerian communities,
      examines these definitions and differentiates between culturally salient
      categories of infertility. In distinguishing between different kinds of childless
      women and those with low fertility, we intend to enhance understandings of
      infertility by considering women's subjective understandings of the condition and
      thus moving beyond the current medical definition. By comparing women's
      experiences in two different ethnic groups in Nigeria, we show how distinct forms
      of kinship structures and social organizations shape the ways low fertility is
      defined, managed, and experienced. 

PMID- 24578251
TI  - Sourcing quality-of-life weights obtained from previous studies: theory and
      reality in Korea.
AB  - BACKGROUND: The quality-of-life weights obtained in previous studies are
      frequently used in cost-utility analyses. The purpose of this study is to
      describe how the values obtained in previous studies are incorporated into the
      industry submissions requesting listing at the Korean National Health Insurance
      (NHI), focusing on the issues discussed in theoretical studies and national
      guidelines. METHODS: The industry submissions requesting listing at the Korean
      NHI from January 2007 until December 2009 were evaluated by two independent
      researchers at the Health Insurance Review and Assessment Service (HIRA).
      Specifically, we observed the methods that were used to pool, predict joint
      health state utilities, and retain consistency within submissions in terms of the
      issues discussed in methodological research papers and recommendations from
      national guidelines. RESULTS: More than half of the submissions used QALY as an
      outcome measure, and most of these submissions were sourced from prior studies.
      Heterogeneous methodologies were frequently used within a submission, with the
      inconsistent use of upper and lower anchors being prevalent. Assumptions behind
      measuring joint health state utilities or pooling multiple values for single
      health states were omitted in all submissions. Most national guidelines were
      rather vague regarding how to predict joint health states, how to select the best
      available value, how to maintain consistency within a submission, and how to
      generalize values obtained from prior studies. CONCLUSIONS: Previously-generated
      values were commonly sourced, but this practice was frequently related to
      inconsistencies within and among submissions. Attention should be paid to the
      consistency and transparency of the value, especially if the value is sourced
      from prior studies.

PMID- 24578252
TI  - Volatile profiles of flavedo, pulp and seeds in Poncirus trifoliata fruits.
AB  - BACKGROUND: Poncirus trifoliata, also known as trifoliate orange, is a tree
      native to China and Korea and widely used all over the world as a rootstock
      breeding material. In this study the differences among the volatile profiles of
      flavedo, pulp and seeds from two cultivars (var. trifoliata and var. monstrosa)
      grown in Italy (Marche, Abruzzo and Sicily) were determined. Headspace solid
      phase microextraction and hydrodistillation techniques were used in combination
      with GC/FID and GC/MS to obtain the volatile profiles of the samples. RESULTS:
      Both techniques permitted the differentiation of fruit parts based on the main
      volatile components: the flavedo was characterized by monoterpene hydrocarbons
      such as limonene and myrcene, the seeds were characterized by sesquiterpene
      hydrocarbons such as (E)-caryophyllene and germacrene D, while the pulp showed an
      intermediate composition. The main differences in volatile profiles obtained by
      the two techniques were analyzed by chemometric techniques such as principal
      component analysis. CONCLUSION: The study did not highlight significant
      differences in volatiles between the two cultivars of trifoliate orange, while
      few differences in the number of volatiles in the fruit parts were revealed by
      the two techniques.

PMID- 24578254
TI  - Significance of the diagnostic categories "atypical" and "suspicious for
      malignancy" in the cytologic diagnosis of solid pancreatic masses.
AB  - Endoscopic ultrasound guided (EUS) fine-needle aspiration (FNA) investigation of
      solid pancreatic lesions has been shown to have good sensitivity and specificity.
      Many lesions can be definitely classified as benign or malignant but some can
      only be cytologically classified as "atypical" or "suspicious for malignancy".
      Risk for malignancy in these indeterminate categories has not been well
      categorized. The cytology records of four University Medical centers were
      searched for all EUS guided FNAs of solid pancreatic lesions. All cases with a
      diagnosis of "atypical", or "suspicious for malignancy" were selected for
      analysis when histologic biopsy or over 18 months clinical follow-up was
      available. Two hundred and ninety-two cases with a diagnosis of "atypical" or
      "suspicious for malignancy" and adequate follow-up were obtained from the
      combined data of the four institutions. The percentage malignant for the
      categories "atypical" and "suspicious for malignancy" were 79.2 and 96.3%,
      respectively. If the category "atypical" was classified as benign and "suspicious
      for malignancy" was classified as malignant, the resulting positive predictive
      value was 96.3 (95% CI: 92.6-98.5) and the negative predictive value 20.8 (95%
      CI: 13.4-30.0). The categories of "atypical" and "suspicious for malignancy"
      stratify risk for malignancy in a fashion, which may aid in patient counseling
      and selection of follow-up protocols. Classification of "suspicious for
      malignancy" as malignant optimizes diagnostic sensitivity and specificity.

PMID- 24578253
TI  - Renal denervation: a novel non-pharmacological approach in heart failure.
AB  - Heart failure is associated with activation of the sympathetic nervous system
      which presumably results in a progression of the syndrome and thereby in poor
      outcome. Renal denervation has shown to be effective in conditions with enhanced
      sympathetic activity like resistant hypertension and metabolic syndrome
      associated with sleep apnea. The first pilot trials assessing the effect of renal
      denervation on signs and symptoms of heart failure in patients with both
      preserved and reduced left ventricular ejection fraction are presently ongoing.
      The results of these studies will determine whether to proceed with larger
      prospective outcome trials. Altogether, renal denervation is a promising novel
      technique that may improve the outcome of patients with sympathetic hyperactivity
      and cardiovascular diseases. 

PMID- 24578255
TI  - Modes of infection and oncogenesis by the Epstein-Barr virus.
AB  - The EBV is a human gamma-herpesvirus associated with various neoplasms. It is
      responsible for causing cancers of B, T, and NK cells as well as cells of
      epithelial origin. Such diversity in target cells and the complicated steps of
      oncogenesis are perplexing when we speculate about the mechanisms of action of
      EBV-positive cancers. Here, we first note three common features that contribute
      to the development and maintenance of EBV-positive cancers: effects of EBV
      oncogenes, immunosuppression and evasion/exploitation of the immune system, and
      genetic and epigenetic predisposition/alteration of the host genome. Then, we
      demonstrate the mechanisms of oncogenesis and the means by which each EBV
      positive cancer develops, with particular focus on the mode of EBV infection. The
      EBV has two alternative life cycles: lytic and latent. The latter is categorized
      into four programs (latency types 0-III) in which latent viral genes are
      expressed differentially depending on the tissue of origin and state of cells.
      The production of viral latent genes tends to decrease with an increase in time,
      and, in an approximate manner, the expression levels of viral genes are inversely
      correlated with the degree of abnormalities in the host genome. Occasional
      execution of the viral lytic cycle also contributes to oncogenesis. Understanding
      this life cycle of the EBV and its relevance in oncogenesis may provide valuable
      clues to the development of effective therapies for the associated cancers.

PMID- 24578256
TI  - Study of nitro-polycyclic aromatic hydrocarbons in particulate matter in
      Dongguan.
AB  - Total suspended and size-segregated atmospheric particles were collected in four
      seasons at three representative points in different functional areas of Dongguan
      City. The detailed size distributions of six nitro-PAHs [2-nitrofluorene (2-NF),
      9-nitroanthracene, 2-nitrofluoranthene (2-NFL), 3-nitrofluoranthene, 1
      nitropyrene, and 2-nitropyrene (2-NP)] were determined by high-performance liquid
      chromatography (HPLC) with UV detection using a binary elution gradient (methanol
      and water). We used a toxicity assessment based on potency equivalency factors
      (PEFs) to estimate the inhalation risk of the particulate matter. The results
      showed that, aside from 2-NF and 2-NFL, the content of the other four nitro-PAHs
      in the microparticles (<0.4 MUm) were more than 20%, a percentage significantly
      higher than other fractions of particulate matter. The seasonal distribution of
      nitro-PAHs shows that their concentrations were higher in the winter, while the
      PAH concentrations were higher in the summer. The study found that secondary
      formation (2-NFL and 2-NP) had a positive correlation with NO x and NO2, but a
      negative correlation with O3. The benzo[a]pyrene equivalent (BaPeq) toxicity of
      particulate matter in Dongguan City ranged from 0.04 to 2.63 ng m(-3), and the
      carcinogenic index ranged from 0.04 * 10(-6) to 2.39 * 10(-6). These values do
      not represent a serious threat to human health.

PMID- 24578257
TI  - High prevalence and genetic diversity of Plasmodium malariae and no evidence of
      Plasmodium knowlesi in Bangladesh.
AB  - Although the prevalence of malaria remains high in parts of Bangladesh, there
      continues to be a substantial shortage of information regarding the less common
      malaria parasites such as Plasmodium malariae or Plasmodium knowlesi. Recent
      studies indicate that P. malariae may be extremely rare, and so far, there are no
      data on the presence (or absence) of P. knowlesi in southeastern Bangladesh.
      Genus- and species-specific nested polymerase chain reaction (PCR) analysis of
      the small subunit ribosomal RNA gene was performed to assess the presence and
      prevalence of P. malariae and P. knowlesi in 2,246 samples originating from
      asymptomatic and febrile participants of a cross-sectional and a febrile
      illnesses study in the Chittagong Hill Tracts in southeastern Bangladesh. P.
      malariae was detected in 60 samples (2.7%) corresponding to 8% of the 746 samples
      giving positive PCR results for Plasmodium sp., mainly because of the high
      prevalence (9.5%) among asymptomatic study participants testing positive for
      malaria. Symptomatic cases were more common (4.3% of all symptomatic malaria
      cases) during the dry season. Parasitemias were low (1,120-2,560/MUl in
      symptomatic and 120-520/MUl in asymptomatic carriers). Symptomatic patients
      presented mild to moderate symptoms like fever, chills, headache, dizziness,
      fatigue and myalgia.Although both the intermediate as well as the definite host
      are known to be endemic in southeastern Bangladesh, no evidence for the presence
      of P. knowlesi was found. We conclude that the role of P. malariae is highly
      underestimated in rural Bangladesh with major implications for malaria control
      and elimination strategies.

PMID- 24578258
TI  - Identification, sequence analysis, and characterization of serine/threonine
      protein kinase 17A from Clonorchis sinensis.
AB  - This is the first report of a novel protein from Clonorchis sinensis (C.
      sinensis), serine/threonine protein kinase 17A (CsSTK17A), which belongs to a
      member of the death-associated protein kinase (DAPK) family known to regulate
      diverse biological processes. The full-length sequence encoding CsSTK17A was
      isolated from C. sinensis adult cDNA plasmid library. Two transcribed isoforms of
      the gene were identified from the genome of C. sinensis. CsSTK17A contains a
      kinase domain at the N-terminus that shares a degree of conservation with the
      DAPK families. Besides, the catalytic domain contains 11 subdomains conserved
      among STKs and shares the highest identity with STK from Schistosoma mansoni
      (55.9%). Three-dimensional structure of CsSTK17A displays the canonical STK fold,
      including the helix C, P-loop, and the activation loop. We obtained recombinant
      CsSTK17A (rCsSTK17A) and anti-rCsSTK17A IgG. The rCsSTK17A could be probed by
      anti-rCsSTK17A rat serum, C. sinensis-infected rat serum and the sera from rats
      immunized with C. sinensis excretory-secretory products, indicating that it is a
      circulating antigen possessing a strong immunocompetence. Moreover, quantitative
      RT-PCR and western blotting analyses revealed that CsSTK17A exhibited the highest
      mRNA and protein expression level in eggs, followed by metacercariae and adult
      worms. Intriguingly, in the immunolocalization assay, CsSTK17A was intensively
      localized to the operculum region of eggs in uterus, as well as the vitelline
      gland of both adult worm and metacercaria, implying that the protein was
      associated with the reproduction and development of C. sinensis. Overall, these
      fundamental studies might contribute to further researches on signaling systems
      of the parasite.

PMID- 24578260
TI  - Cytotoxic anthraquinone dimers from Melandrium firmum.
AB  - Two new anthraquinone dimers, melrubiellin A (1) and melrubiellin B (2), were
      isolated from the aerial part of Melandrium firmum Rohrbach, along with seven
      known compounds (3-9). The structures of these compounds were elucidated by
      spectral analyses, including 1D and 2D NMR (COSY, HMQC, HMBC and NOESY)
      experiments. Compound 1 and 2 exhibited significant cytotoxicity towards HeLa,
      NCI-H460, Hep G2, Hep 3B and MKN-28 cell lines with IC50 values ranging from 5.26
      to 81.16 MUM.

PMID- 24578259
TI  - A 4-years monitoring of Hypoderma diana in horses from the Czech Republic.
AB  - The occurrence of Hypoderma diana (Diptera: Hypodermatidae) in a herd of 15
      horses was observed during a 4-year period (2010-2013) in northwest Bohemia.
      During this period, infestation by the warble fly H. diana increased from 12.5%
      in 2010 to 53.3% in 2013. Nodules were observed on the neck, back, stomach, legs,
      and head. The incidence of H. diana was probably influenced by the presence of a
      specific host mouflon (Ovis orientalis musimon).

PMID- 24578261
TI  - Comparison of chronic kidney disease prevalence examined by the chronic kidney
      disease epidemiology collaboration equation with that by the modification of diet
      in renal disease equation in Korean adult population.
AB  - BACKGROUND: The new estimated glomerular filtration (eGFR) equation, Chronic
      Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, was recently
      introduced. We compared the prevalence of CKD examined by the CKD-EPI equation
      with that by the Modification of Diet in Renal Disease (MDRD) equation. METHODS:
      We analyzed the data from a total of 14,605 Korean adults (age >=20 years), who
      were enrolled in the Korean National Health and Nutrition Examination Survey in
      2007, 2009, and 2010. CKD stages 1 and 2 were defined as eGFR >=60 mL/min/1.73
      m(2) with proteinuria measured by dipstick. CKD stages 3-5 were defined as eGFR
      <60 mL/min/1.73 m(2) . RESULTS: The eGFRs calculated by the CKD-EPI equation were
      higher than those calculated by the MDRD equation (P < 0.001), especially in
      women and young people. The prevalence of CKD stages 3-5 calculated by the MDRD
      equation was 6.8%, 3.0%, and 3.0% in 2007, 2009, and 2010, respectively. The
      prevalence of CKD stages 3-5 calculated by CKD-EPI equation was 7.7%, 2.7%, and
      2.6% in 2007, 2009, and 2010, respectively. When defining the CKD using the CKD
      EPI equation, 55 (32.7%) of 350 cases were reclassified into more advanced stages
      and 295 cases (67.3%) were reclassified into less-advanced stages. CONCLUSION:
      The CKD-EPI equation caused an overall low prevalence of CKD compared to the
      MDRD. Therefore, CKD-EPI equation might be helpful to prevent an overestimation
      of CKD.

PMID- 24578262
TI  - Estimating striae of Retzius periodicity nondestructively using partial counts of
      perikymata.
AB  - Accurate age estimations for enamel formation and the timing of enamel hypoplasia
      have traditionally only been available through histological analyses of dental
      thin sections, which is a difficult and destructive process. However, an
      association between striae of Retzius periodicity, crucial for accurate aging,
      and the total number of striae in imbricational enamel has been reported in the
      literature. This means periodicity can be estimated nondestructively but is
      reliant on all perikymata being visible along the crown surface. Therefore,
      crowns with worn or damaged surfaces may not be able to be assessed, potentially
      limiting sample sizes. We tested this relationship in a modern New Zealand sample
      and investigated whether reliable associations might be identified using only
      partial perikymata counts from the cervical half of the crown. Using mandibular
      canines (n = 11), the distribution of perikymata per decile was recorded using
      high definition replica surfaces. Thin sections of the same crowns were used to
      assess periodicity histologically along with striae of Retzius distributions. A
      strong correlation between total striae numbers and periodicity was also
      identified in our sample. Furthermore, we report strong correlations that allow
      periodicity to be estimated from perikymata counts using only 10% of crown height
      when certain deciles are used. Based on these findings, we propose a simple
      matrix that can be developed for nondestructively estimating periodicity based on
      the range of perikymata counts in the sixth to ninth deciles.

PMID- 24578263
TI  - Induction of labor compared to dilation and evacuation for postmortem analysis.
AB  - OBJECTIVE: This study aimed to evaluate the ability to obtain autopsy and
      cytogenetics after midtrimester termination. METHODS: A retrospective cohort
      study of women undergoing termination, via induction or dilation and evacuation
      (D&E), at 16 0/7-23 6/7 weeks was performed. Exclusion criteria were elective
      termination, preterm labor, PPROM, and no autopsy or cytogenetic exam performed.
      The ability to obtain cytogenetics and autopsy as well as complications rates
      were compared between the two groups with Chi-square tests. RESULTS: Of the 469
      women who met the inclusion criteria, 158 had an induction and 312 had a D&E. The
      induction of labor group had higher mean gestational ages, p < 0.01. Successful
      autopsy was more likely in the induction group, 94.3%, versus D&E group, 34.7%, p
      = 0.01. There was no difference in ability to obtain cytogenetics between the two
      groups, 89.1% in the induction group, and 92.3% in D&E group, p = 0.4. There was
      a difference in the total complication rates between the groups, 9.8% (26) in the
      induction versus 6.4% (20) in the D&E group, p < 0.01; however, there was no
      difference in major complications. CONCLUSIONS: Midtrimester terminations by
      induction were more likely to have successful autopsies when compared with D&E.
      The ability to obtain cytogenetics was similar regardless of termination mode.

PMID- 24578265
TI  - Advanced treatment of refractory organic pollutants in petrochemical industrial
      wastewater by bioactive enhanced ponds and wetland system.
AB  - A large-scale combined ponds-wetland system was applied for advanced treatment of
      refractory pollutants in petrochemical industrial wastewater. The system was
      designed to enhance bioactivity and biological diversity, which consisted of
      anaerobic ponds (APs), facultative ponds (FPs), aerobic pond and wetland. The
      refractory pollutants in the petrochemical wastewater to be treated were
      identified as alkanes, chloroalkanes, aromatic hydrocarbons, and olefins, which
      were significantly degraded and transformed along with the influent flowing
      through the enhanced bioactive ponds-wetland system. 8 years of recent
      operational data revealed that the average removal rate of stable chemical oxygen
      demand (COD) was 42.7 % and that influent COD varied from 92.3 to 195.6 mg/L.
      Final effluent COD could reach 65.8 mg/L (average). COD removal rates were high
      in the APs and FPs and accounted for 75 % of the total amount removed. This
      result indicated that the APs and FPs degraded refractory pollutants through the
      facilitation of bacteria growth. The changes in the community structures of major
      microbes were assessed by 16SrDNA-denaturing gradient gel electrophoresis. The
      same analysis was used to identify the main bacterial function for the removal of
      refractory pollutants in the APs and FPs. The APs and FPs displayed similar
      microbial diversities, and some of the identified bacteria degraded and removed
      refractory pollutants. The overall results proved the applicability, stability,
      and high efficiency of the ponds-wetland system with enhanced bioactivity in the
      advanced removal of refractory pollutants from petrochemical industrial
      wastewater.

PMID- 24578266
TI  - The role of traditional varieties of tomato as sources of functional compounds.
AB  - BACKGROUND: Traditional varieties of tomato, usually associated with excellent
      organoleptic quality, are increasingly appreciated in European quality markets. A
      collection of 126 populations of 16 traditional varieties from the east of Spain
      (a secondary diversity center for tomato) have been evaluated over 2 years in
      order to determine their potential value as sources of functional compounds,
      including ascorbic acid, lycopene, beta-carotene and total phenolic content.
      RESULTS: Population and population * year interaction significantly affected
      lycopene and ascorbic acid contents, while year effect was also significant for
      beta-carotene. Despite finding some global trends in certain varieties concerning
      their functional value, high levels of variation have been found at the intra
      varietal level. Populations with high levels of the compounds analysed have been
      found, as well as different levels of intra-population and inter-year variation.
      Maximum mean contents for both years have reached 308 mg kg(-1) ascorbic acid,
      130 mg kg(-1) lycopene, 30 mg kg(-1) beta-carotene and 89 mg caffeic acid 100 g(
      1) total phenolic contents, though it is difficult to identify accessions with
      joint high values of the three compounds. CONCLUSION: These results open the
      possibility to promote traditional materials as sources of functional compounds,
      thus strengthening their quality niches and consolidating their price premium.
      Additionally, these materials could also be used in breeding programs for
      quality.

PMID- 24578268
TI  - Genome Sequence of the Mucoromycotina Fungus Umbelopsis isabellina, an Effective
      Producer of Lipids.
AB  - Umbelopsis isabellina is a fungus in the subdivision Mucoromycotina, many members
      of which have been shown to be oleaginous and have become important organisms for
      producing oil because of their high level of intracellular lipid accumulation
      from various feedstocks. The genome sequence of U. isabellina NBRC 7884 was
      determined and annotated, and this information might provide insights into the
      oleaginous properties of this fungus. 

PMID- 24578264
TI  - Activation of PI3K and R-Ras signaling promotes the extension of sensory axons on
      inhibitory chondroitin sulfate proteoglycans.
AB  - Chondroitin sulfate proteoglycans (CSPGs) are extracellular inhibitors of axon
      extension and plasticity, and cause growth cones to exhibit dystrophic behaviors.
      Phosphoinositide 3-kinase (PI3K) is a lipid kinase activated by axon growth
      promoting signals. In this study, we used embryonic chicken dorsal root ganglion
      neurons to determine if CSPGs impair signaling through PI3K. We report that CSPGs
      inhibit PI3K signaling in axons and growth cones, as evidenced by decreased
      levels of phosphorylated downstream kinases (Akt and S6). Direct activation of
      PI3K signaling, using a cell permeable phosphopeptide (PI3Kpep), countered the
      effects of CSPGs on growth cones and axon extension. Both overnight and acute
      treatment with PI3Kpep promoted axon extension on CSPG-coated substrates. The R
      Ras GTPase is an upstream positive regulator of PI3K signaling. Expression of
      constitutively active R-Ras promoted axon extension and growth cone elaboration
      on CSPGs and permissive substrata. In contrast, an N-terminus-deleted
      constitutively active R-Ras, deficient in PI3K activation, promoted axon
      extension but not growth cone elaboration on CSPGs and permissive substrata.
      These data indicate that activation of R-Ras-PI3K signaling may be a viable
      approach for manipulating axon extension on CSPGs.

PMID- 24578267
TI  - Mass cytometry to decipher the mechanism of nongenetic drug resistance in cancer.
AB  - Nongenetic resistance has recently been described as a major impediment to
      effective cancer therapy. Nongenetic resistance is challenging to study since it
      occurs nonuniformly, even in cell lines, and can involve the interplay of
      multiple survival pathways. Until recently, no technology allowed measurement of
      large-scale alterations in survival pathways with single-cell resolution. Mass
      cytometry, a flow-based technique in which the activation of up to 50 proteins
      can be measured simultaneously in single-cell, now provides the ability to
      examine nongenetic resistance on the functional level on a cell-by-cell basis.
      The application of mass cytometry, in combination with new bioinformatic
      techniques, will allow fundamental questions on nongenetic resistance to be
      addressed: Is resistance caused by selection of cells with a pre-existing
      survival phenotype or induction of a survival program? Which survival pathways
      are necessary for nongenetic resistance and how do they interact? Currently, mass
      cytometry is being used to investigate the mechanism of nongenetic resistance to
      TRAIL-induced apoptosis. The approaches being developed to understand resistance
      to TRAIL will likely be applied to elucidate the mechanisms of nongenetic
      resistance broadly and in the clinic. 

PMID- 24578269
TI  - Functional Analysis Using Whole-Genome Sequencing of a Drug-Sensitive
      Mycobacterium tuberculosis Strain from Peru.
AB  - We report the whole-genome sequence of a Latin American-Mediterranean (LAM)
      lineage drug-sensitive Mycobacterium tuberculosis strain from Peru, INS-SEN. The
      functional analysis revealed more mutations in secondary metabolite biosynthesis,
      transport, and catabolism (clusters of orthologous groups [COG] category Q) than
      for other LAM-sensitive strains. This study contributes to the understanding of
      the genomic diversity of drug-sensitive M. tuberculosis. 

PMID- 24578270
TI  - Evidence of Clonal Expansion in the Genome of a Multidrug-Resistant Mycobacterium
      tuberculosis Clinical Isolate from Peru.
AB  - We report the genome sequence of Mycobacterium tuberculosis INS-MDR from Peru, a
      multidrug-resistant tuberculosis (MDR-TB) and Latin American-Mediterranean (LAM)
      lineage strain. Our analysis showed mutations related to drug resistance in the
      rpoB (D516V), katG (S315T), kasA (G269S), and pncA (Q10R) genes. Our evidence
      suggests that INS-MDR may be a clonal expansion related to the African strain KZN
      1435. 

PMID- 24578271
TI  - Draft Genome Sequence of Pedobacter sp. Strain V48, Isolated from a Coastal Sand
      Dune in the Netherlands.
AB  - Pedobacter sp. strain V48 participates in an interaction with Pseudomonas
      fluorescens which elicits interaction-induced phenotypes. We report the draft
      genome sequence of Pedobacter sp. V48, consisting of 6.46 Mbp. The sequence will
      contribute to improved understanding of the genus and facilitate genomic analysis
      of the model interspecies interaction with P. fluorescens. 

PMID- 24578272
TI  - Whole-genome sequence of muju virus, an arvicolid rodent-borne hantavirus.
AB  - The complete genome sequence of Muju virus was determined from lung tissue
      samples of three royal voles (Myodes regulus) captured in Gangwon province in the
      Republic of Korea. Since few whole genome sequences of hantaviruses are
      available, this sequence may help to clarify the molecular phylogeny of arvicolid
      rodent-borne hantaviruses. 

PMID- 24578273
TI  - Insight into the Draft Genome Sequence of Human Isolate Lactobacillus rhamnosus
      LR231, a Bacterium with Probiotic Potential.
AB  - Lactobacillus rhamnosus strain LR231 was isolated from the feces of healthy human
      subjects. It is observed to be a potential probiotic strain, having a broad
      spectrum of antimicrobial activity against a wide range of human pathogens and
      food pathogens. Here, we provide the 2.59-Mb draft genome sequence of L.
      rhamnosus LR231. 

PMID- 24578274
TI  - Islet-1 overexpression in human mesenchymal stem cells promotes vascularization
      through monocyte chemoattractant protein-3.
AB  - The LIM-homeobox transcription factor islet-1 (ISL1) has been proposed to mark a
      cardiovascular progenitor cell lineage that gives rise to cardiomyocytes,
      endothelial cells, and smooth muscle cells. The aim of this study was to
      investigate whether forced expression of ISL1 in human mesenchymal stem cells
      (hMSCs) influenced the differentiation capacity and angiogenic properties of
      hMSCs. The lentiviral vector, EF1alpha-ISL1, was constructed using the Multisite
      Gateway System and used to transduce hMSCs. We found that ISL1 overexpression did
      not alter the proliferation, migration, or survival of hMSCs or affect their
      ability to differentiate into osteoblasts, adipocytes, cardiomyocytes, or
      endotheliocytes. However, ISL1-hMSCs differentiated into smooth muscle cells more
      efficiently than control hMSCs. Furthermore, conditioned medium from ISL1-hMSCs
      greatly enhanced the survival, migration, and tube-formation ability of human
      umbilical vein endothelial cells (HUVECs) in vitro. In vivo angiogenesis assays
      also showed much more vascular-like structures in the group cotransplanted with
      ISL1-hMSCs and HUVECs than in the group cotransplanted with control hMSCs and
      HUVECs. Quantitative RT-PCR and antibody arrays detected monocyte chemoattractant
      protein-3 (MCP3) at a higher level in conditioned medium from ISL1-hMSCs cultures
      than in conditioned medium from control hMSCs. Neutralization assays showed that
      addition of an anti-MCP3 antibody to ISL1-hMSCs-conditioned medium efficiently
      abolished the angiogenesis-promoting effect of ISL1-hMSCs. Our data suggest that
      overexpression of ISL1 in hMSCs promotes angiogenesis in vitro and in vivo
      through increasing secretion of paracrine factors, smooth muscle differentiation
      ability, and enhancing the survival of HUVECs.

PMID- 24578275
TI  - Quiet T1-weighted imaging using PETRA: initial clinical evaluation in
      intracranial tumor patients.
AB  - PURPOSE: To compare the lesion contrast and signal to noise ratio (SNR) obtained
      with T1-weighted pointwise encoding time reduction with radial acquisition
      (PETRA) to those of Magnetization-Prepared RApid Gradient-Echo (MPRAGE) for
      contrast-enhanced imaging of primary and metastatic intracranial tumors, and to
      investigate whether PETRA is able to reduce acoustic noise for improved patient
      comfort. MATERIALS AND METHODS: Fifteen patients with intracranial tumors
      underwent 3 Tesla MRI including inversion-prepared PETRA and MPRAGE. The two
      sequences had comparable scan times, spatial resolution and spatial coverage.
      "Tumor conspicuity" was rated qualitatively by two radiologists, while enhancing
      lesion-to-white matter contrast to noise ratio (CNR) and white-matter SNR were
      analyzed quantitatively using paired t-tests. The acoustic noise generated by
      each sequence was measured. RESULTS: Qualitative rating of "tumor conspicuity" by
      two radiologists resulted in nearly identical average scores for the two
      sequences. Quantitative analyses revealed that (i) there was no significant
      difference between the mean CNR values of the two sequences (P = 0.57), (ii) the
      mean SNR of PETRA was significantly higher than that of MPRAGE (P < 0.01), and
      (iii) the mean sound level of PETRA was significantly lower than that of MPRAGE
      (P < 0.01). CONCLUSION: Inversion-prepared PETRA was found to be viable as a
      quiet alternative to MPRAGE for contrast-enhanced T1-weighted studies of
      intracranial tumors.

PMID- 24578276
TI  - ATP-stabilized amorphous calcium carbonate nanospheres and their application in
      protein adsorption.
AB  - Calcium carbonate is a common substance found in rocks worldwide, and is the main
      biomineral formed in shells of marine organisms and snails, pearls and eggshells.
      Amorphous calcium carbonate (ACC) is the least stable polymorph of calcium
      carbonate, which is so unstable under normal conditions that it is difficult to
      be prepared in vitro because it rapidly crystallizes to form one of the more
      stable polymorphs in aqueous solution. Herein, we report the successful synthesis
      of highly stable ACC nanospheres in vitro using adenosine 5'-triphosphate
      disodium salt (ATP) as a stabilizer. The effect of ATP on the stability of ACC
      nanospheres is investigated. Our experiments show that ATP plays an unique role
      in the stabilization of ACC nanospheres in aqueous solution. Moreover, the as
      prepared ACC nanospheres are highly stable in phosphate buffered saline for a
      relatively long period of time (12 days) even under relatively high
      concentrations of calcium and phosphate ions. The cytotoxicity tests show that
      the as-prepared highly stable ACC nanospheres have excellent biocompatibility.
      The highly stable ACC nanospheres have high protein adsorption capacity, implying
      that they are promising for applications in biomedical fields such as drug
      delivery and protein adsorption. 

PMID- 24578277
TI  - Catalysis and inactivation of tyrosinase in its action on hydroxyhydroquinone.
AB  - Hydroxyhydroquinone (HHQ) was characterized kinetically as a tyrosinase
      substrate. A kinetic mechanism is proposed, in which HHQ is considered as a
      monophenol or as an o-diphenol, depending on the part of the molecule that
      interacts with the enzyme. The kinetic parameters obtained from an analysis of
      the measurements of the initial steady state rate of 2-hydroxy p-benzoquinone
      formation were kcatapp=229.0+/-7.7 s(-1) and KMapp,HHQ=0.40+/-0.05 mM.
      Furthermore, the action of tyrosinase on HHQ led to the enzyme's inactivation
      through a suicide inactivation mechanism. This suicide inactivation process was
      characterized kinetically by lambdamaxapp (the apparent maximum inactivation
      constant) and r, the number of turnovers made by 1 mol of enzyme before being
      inactivated. The values of lambdamaxapp and r were (8.2+/-0.1)*10(-3) s(-1) and
      35,740+/-2,548, respectively.

PMID- 24578279
TI  - Phlebographic study between patients with MS and control subjects: the ethical
      profile.

PMID- 24578278
TI  - MR quantitative susceptibility imaging for the evaluation of iron loading in the
      brains of patients with beta-thalassemia major.
AB  - BACKGROUND AND PURPOSE: Patients with beta-thalassemia require blood transfusion
      to prolong their survival, which could cause iron overload in multiple organs,
      including the heart, liver, and brain. In this study, we aimed to quantify iron
      loading in the brains of patients with beta-thalassemia major through the use of
      MR quantitative susceptibility imaging. MATERIALS AND METHODS: Thirty-one
      patients with thalassemia with a mean (+/- standard deviation) age of 25.3 (+/
      5.9) years and 33 age-matched healthy volunteers were recruited and underwent MR
      imaging at 3T. Quantitative susceptibility images were reconstructed from a 3D
      gradient-echo sequence. Susceptibility values were measured in the caudate
      nucleus, putamen, globus pallidus, red nucleus, substantia nigra, dentate
      nucleus, and choroid plexus. General linear model analyses were performed to
      compare susceptibility values of different ROIs between the patients with
      thalassemia and healthy volunteers. RESULTS: Of the 31 patients, 27 (87.1%) had
      abnormal iron deposition in one of the ROIs examined. Significant positive age
      effect on susceptibility value was found in the putamen, dentate nucleus,
      substantia nigra, and red nucleus (P = .002, P = .017, P = .044, and P = .014,
      respectively) in the control subjects. Compared with healthy control subjects,
      patients with thalassemia showed significantly lower susceptibility value in the
      globus pallidus (P < .001) and substantia nigra (P = .003) and significantly
      higher susceptibility value in the red nucleus (P = .021) and choroid plexus (P <
      .001). CONCLUSIONS: A wide range of abnormal susceptibility values, indicating
      iron overloading or low iron content, was found in patients with thalassemia. MR
      susceptibility imaging is a sensitive method for quantifying iron concentration
      in the brain and can be used as a potentially valuable tool for brain iron
      assessment.

PMID- 24578280
TI  - Use of flow-diverting devices in fusiform vertebrobasilar giant aneurysms: a
      report on periprocedural course and long-term follow-up.
AB  - BACKGROUND AND PURPOSE: Fusiform vertebrobasilar giant aneurysms are a rare (<1%
      of all intracranial aneurysms) but challenging aneurysm subtype. Little data are
      available on the natural history of this aneurysm subtype and the impact of the
      use of flow-diverting stents on the long-term clinical and imaging follow-up. In
      this article, we present our experience with the treatment of fusiform
      vertebrobasilar giant aneurysms by flow diverting stents. We aim to stimulate a
      discussion of the best management paradigm for this challenging aneurysm subtype.
      MATERIALS AND METHODS: We retrospectively identified 6 patients with fusiform
      vertebrobasilar giant aneurysms who had been treated with flow-diverting stents
      between October 2009 and March 2012 in our center. The available data were re
      evaluated. The modified Rankin Scale score was assessed before intervention,
      during the stay in hospital, and at discharge. RESULTS: Six patients were
      identified (all male; age range, 49-71 years; median age, 60 years). Handling of
      material was successful in all cases. No primary periprocedural complications
      occurred. The mean follow-up was 13 months (15 days to 29 months). During follow
      up, 3 of 6 patients had recurrent cerebral infarctions, but no patient
      experienced SAH. Two patients presented with acute thrombotic stent occlusion.
      The modified Rankin Scale score was not higher than 3 in any of the cases before
      intervention, whereas the best mRS score at the last follow-up was 5. Four of 6
      patients died during follow-up. CONCLUSIONS: Endovascular treatment of fusiform
      vertebrobasilar giant aneurysms with flow-diverting devices is feasible from a
      technical point of view; however, changes in hemodynamics with secondary
      thrombosis are not predictable. We currently do not intend to treat fusiform
      vertebrobasilar giant aneurysms with flow-diverting devices until we have further
      understanding of the pathophysiology, natural history, and hemodynamic effects of
      flow diversion.

PMID- 24578281
TI  - Regional neuronal network failure and cognition in late-onset sporadic Alzheimer
      disease.
AB  - BACKGROUND AND PURPOSE: The severe cognitive deficits in Alzheimer disease are
      associated with structural lesions in gray and white matter in addition to
      changes in synaptic function. The current investigation studied the breakdown of
      the structure and function in regional networks involving the Papez circuit and
      extended neocortical association areas. MATERIALS AND METHODS: Cortical
      volumetric and diffusion tensor imaging (3T MR imaging), positron-emission
      tomography with (18)F fluorodeoxyglucose on a high-resolution research tomograph,
      and comprehensive neuropsychological assessments were performed in patients with
      late-onset sporadic Alzheimer disease, those with mild cognitive impairment, and
      elderly healthy controls. RESULTS: Atrophy of the medial temporal lobes was the
      strongest and most consistent abnormality in patients with mild cognitive
      impairment and Alzheimer disease. Atrophy in the temporal, frontal, and parietal
      regions was most strongly related to episodic memory deficits, while deficits in
      semantic cognition were also strongly related to reductions of glucose metabolism
      in the posterior cingulate cortex and temporoparietal regions. Changes in
      fractional anisotropy within white matter tracts, particularly in the left
      cingulum bundle, uncinate fasciculus, superior longitudinal fasciculus, and
      inferior fronto-occipital fasciculus, were significantly associated with the
      cognitive deficits in multiple regression analyses. Posterior cingulate and
      orbitofrontal metabolic deficits appeared to be related to microstructural
      changes in projecting white matter tracts. CONCLUSIONS: Many lesioned network
      components within the Papez circuit and extended neocortical association areas
      were significantly associated with cognitive dysfunction in both mild cognitive
      impairment and late-onset sporadic Alzheimer disease. Hippocampal atrophy was the
      most prominent lesion, with associated impairment of the uncinate and cingulum
      white matter microstructures and hippocampal and posterior cingulate metabolic
      impairment.

PMID- 24578282
TI  - Update on the surgical management of idiopathic intracranial hypertension.
AB  - Idiopathic intracranial hypertension (IIH) is a disorder of elevated intracranial
      pressure due to an unknown cause. In most cases, IIH can be managed with medical
      therapy and weight reduction. Surgical treatment of IIH is reserved for patients
      who cannot tolerate medical therapy, are nonadherent to medical therapy, develop
      progressive symptoms despite maximal medical therapy, or present with fulminant
      visual loss. To date, there has been no randomized controlled trial to evaluate
      the surgical treatment of IIH, and our current knowledge of the efficacy and
      complications of these procedures is based on retrospective and observational
      studies. This review discusses the indications for surgical intervention in IIH
      and provides an overview of the recently published data on the efficacy and
      complications of these interventions. A surgical management algorithm is also
      presented to guide the clinician when evaluating a patient with IIH. 

PMID- 24578283
TI  - MMP-9 expression increases according to the grade of squamous intraepithelial
      lesion in cervical smears.
AB  - Studies about cervical carcinogenesis have demonstrated the increased expression
      of matrix-metalloproteinase (MMP) according to the grade of cervical
      intraepithelial lesions. Considering the importance of innovative techniques to
      introduce noninvasive and rapid diagnoses for patients, this study aimed to
      perform MMP-9 immunocytochemistry in cervical smears according to the
      cytopathological diagnoses, in order to monitor MMP activity in cervical smears.
      This cross-sectional study investigated the expression of MMP-9 in normal
      cervical smears, inflammatory cervical smears, squamous intraepithelial lesions,
      and cervical carcinoma. Cervical smears from 630 women were collected for
      cytopathological diagnoses and immunocytochemistry. Women with squamous
      intraepithelial lesions showed an increase in MMP-9 expression, with moderate to
      intense staining occurring with increasing cervical lesion grade. The prevalence
      of moderate to intense MMP-9 staining was 9% in normal cervical smears, 12% in
      cervical inflammation, 24% in low-grade squamous intraepithelial lesion (LSIL),
      92% in high-grade squamous intraepithelial lesions (HSIL) and 100% in cervical
      carcinoma cases. In the specific case of LSIL, we found that association with MMP
      9 is more evident when there is the simultaneous presence of an infectious agent.
      Thus, the expression of MMP-9 in cervical smears increases according to the grade
      of cervical lesion and LSIL in the presence of infectious agents showed higher
      MMP-9 expression than women with LSIL without infectious agents.

PMID- 24578284
TI  - Modeling the seasonality of Anopheles gambiae s.s. biting rates in a South Benin
      sanitary zone.
AB  - BACKGROUND: Efficient malaria vector control requires knowledge of spatio
      temporal vector dynamics. We have classified village groups according to the
      biting rate profiles of both Anopheles coluzzii and An. gambiae, the major
      malaria vectors in these villages. METHODS: Mosquitoes were captured by human
      bait in 28 South Benin villages during 2009. Both An. coluzzii and An. gambiae
      counts in each village were standardized to focus on changes in the vector biting
      rate over time. Latent class trajectory modeling, allowing for random intercept
      at the 'village' level, was adjusted to standardized values. RESULTS: The
      villages could be classified into two groups with distinct vector biting rate
      profiles (continuous/transient). This classification helped creating a map of
      vector biting rates in the area. The biting rate profiles were found to be
      significantly correlated with mean rainfall, altitude, average number of larval
      sites, and average normalized difference vegetation index. CONCLUSIONS: In highly
      malaria-prone regions, knowledge of vector biting rate profiles is important to
      improve vector control interventions. A similar methodology may be applied to
      study the biting rate profiles of other vector-borne infections.

PMID- 24578285
TI  - Sensitivity of Salmonella YG5161 for detecting PAH-associated mutagenicity in air
      particulate matter.
AB  - The Salmonella/microsome assay is the most used assay for the evaluation of air
      particulate matter (PM) mutagenicity and a positive correlation between strain
      TA98 responses and benzo[a]pyrene (B[a]P) levels in PM has been found. However,
      it seems that the major causes of PM mutagenicity in this assay are the nitro and
      oxy-PAHs. Salmonella YG5161, a 30-times more responsive strain to B[a]P has been
      developed. To verify if YG5161 strain was sufficiently sensitive to detect
      mutagenicity associated with B[a]P mutagenicity, PM samples were collected in
      Brazil and Sweden, extracted with toluene and tested in the Salmonella/microsome
      microsuspension assay. PAHs and B[a]P were determined and the extracts were
      tested with YG5161 and its parental strain TA1538. The extracts were also tested
      with YG1041 and its parental strain TA98. For sensitivity comparisons, we tested
      B[a]P and 1-nitropyrene (1-NP) using the same conditions. The minimal effective
      dose of B[a]P was 155 ng/plate for TA1538 and 7 ng/plate for YG5161. Although the
      maximum tested dose, 10 m(3) /plate containing 9 ng of B[a]P in the case of
      Brazilian sample, was sufficient to elicit a response in YG5161, mutagenicity was
      detected at a dose as low as 1 m(3) /plate (0.9 ng). This is probably caused by
      nitro-compounds that have been shown to be even more potent than B[a]P for
      YG5161. It seems that the mutagenicity of B[a]P present in PM is not detectable
      even with the use of YG5161 unless more efficient separation to remove the nitro
      compounds from the PAH extract is performed.

PMID- 24578286
TI  - Involvement of Sac1 phosphoinositide phosphatase in the metabolism of
      phosphatidylserine in the yeast Saccharomyces cerevisiae.
AB  - Sac1 is a phosphoinositide phosphatase that preferentially dephosphorylates
      phosphatidylinositol 4-phosphate. Mutation of SAC1 causes not only the
      accumulation of phosphoinositides but also reduction of the phosphatidylserine
      (PS) level in the yeast Saccharomyces cerevisiae. In this study, we characterized
      the mechanism underlying the PS reduction in SAC1-deleted cells. Incorporation of
      (32) P into PS was significantly delayed in sac1? cells. Such a delay was also
      observed in SAC1- and PS decarboxylase gene-deleted cells, suggesting that the
      reduction in the PS level is caused by a reduction in the rate of biosynthesis of
      PS. A reduction in the PS level was also observed with repression of STT4
      encoding phosphatidylinositol 4-kinase or deletion of VPS34 encoding
      phophatidylinositol 3-kinase. However, the combination of mutations of SAC1 and
      STT4 or VPS34 did not restore the reduced PS level, suggesting that both the
      synthesis and degradation of phosphoinositides are important for maintenance of
      the PS level. Finally, we observed an abnormal PS distribution in sac1? cells
      when a specific probe for PS was expressed. Collectively, these results suggested
      that Sac1 is involved in the maintenance of a normal rate of biosynthesis and
      distribution of PS.

PMID- 24578287
TI  - High-throughput biosensor discriminates between different algal H2 
      photoproducing strains.
AB  - A number of species of microalgae and cyanobacteria photosynthetically produce H2
      gas by coupling water oxidation with the reduction of protons to molecular
      hydrogen, generating renewable energy from sunlight and water. Photosynthetic H2
      production, however, is transitory, and there is considerable interest in
      increasing and extending it for commercial applications. Here we report a Petri
      plate version of our previous, microplate-based assay that detects photosynthetic
      H2 production by algae. The assay consists of an agar overlay of H2 -sensing
      Rhodobacter capsulatus bacteria carrying a green fluorescent protein that
      responds to H2 produced by single algal colonies in the bottom agar layer. The
      assay distinguishes between algal strains that photoproduce H2 at different
      levels under high light intensities, and it does so in a simple, inexpensive, and
      high-throughput manner. The assay will be useful for screening both natural
      populations and mutant libraries for strains having increased H2 production, and
      useful for identifying various genetic factors that physiologically or
      genetically alter algal hydrogen production.

PMID- 24578288
TI  - Positive peritoneal cytology in patients with endometrial cancer: continued
      controversy despite shift in staging.

PMID- 24578289
TI  - A randomized trial of a prenatal genetic testing interactive computerized
      information aid.
AB  - OBJECTIVE: The aim of this study was to determine whether an interactive computer
      program could improve patient knowledge regarding genetic screening and
      diagnostic concepts. METHODS: In this randomized trial, women 6-26 weeks'
      gestation were assigned to standard care with provider-based counseling or to
      augmented counseling with an interactive computer program. The computer-based
      tool conveyed information about genetic testing options. Women were administered
      a 23-item test of content knowledge immediately and 2-4 weeks after exposure.
      Test scores were compared between groups at both points using T-tests. RESULTS: A
      total of 150 women were randomized equally between groups. Groups were similar
      with regard to demographic characteristics. Women randomized to the interactive
      tool correctly answered a significantly greater proportion of questions than
      those who received standard counseling (69.4% +/- 14.2% vs. 46.0% +/- 15.2%, p <
      0.001) on the immediate questionnaire. One hundred and twenty-three (82%)
      participants participated in the follow-up test. Women randomized to the tool
      continued to correctly answer a significantly greater proportion of questions
      (60.6% +/- 16% vs. 49.7% +/- 18.9%, p = 0.001). Education, health literacy,
      electronic health literacy, and other discussions with providers were not
      associated with a differential benefit from the educational intervention.
      CONCLUSION: A patient-directed interactive computer program may help providers to
      convey relevant information about genetic screening and diagnostic concepts.

PMID- 24578290
TI  - Esterification of fatty acids by Penicillium crustosum lipase in a membrane
      reactor.
AB  - BACKGROUND: This study investigated the performance of a membrane reactor system
      for esterification of oleic acid and butyric acid with ethanol by Penicillium
      crustosum lipase using polyethersulfone membranes with molecular weight cut-offs
      of 30, 60 and 100 kDa at pressures up to 200 kPa. RESULTS: The confinement of
      lipase with 60 and 100 kDa membranes showed the best results. The esterification
      of butyric acid in the membrane reactor and with free lipase showed higher
      conversions than those obtained with oleic acid, since the system operated with
      oleic acid was more subject to fouling and thus could not be run for repeated
      cycles. CONCLUSION: The confinement of lipase from P. crustosum in a membrane
      reactor was possible, resulting in the satisfactory conversion of butyric acid to
      ethyl butyrate with the possibility of reuse of the immobilized enzyme.

PMID- 24578291
TI  - Hypoxia enhances the radioresistance of mouse mesenchymal stromal cells.
AB  - Mesenchymal stromal cells (MSCs) are radioresistant bone marrow progenitors that
      support hematopoiesis and its reconstitution following total body irradiation.
      MSCs reside in hypoxic niches within the bone marrow and tumor microenvironments.
      The DNA damage response (DDR) represents a network of signaling pathways that
      enable cells to activate biological responses to DNA damaging agents. Hypoxia
      mediated alterations in the DDR contribute to the increased radioresistance of
      hypoxic cancer cells, limiting therapeutic efficacy. The DDR is important in
      mediating mouse MSC radioresistance. However, the effects of hypoxia on MSC
      radioresistance are currently unknown. In this report, hypoxia was found to (a)
      increase MSC proliferation rate and colony size; (b) increase long-term survival
      post-irradiation (IR), and (c) improve MSC recovery from IR-induced cell cycle
      arrest. DNA double-strand break (DSB) repair in MSCs was upregulated in hypoxia,
      accelerating the resolution of highly genotoxic IR-induced DNA DSBs. In addition,
      HIF-1alpha was found to contribute to this enhanced DSB repair by regulating (a)
      the expression of DNA ligase IV and DNA-PKcs and (b) Rad51 foci formation in
      response to DNA DSBs in hypoxic MSCs. We have demonstrated, for the first time,
      that hypoxia enhances mouse MSC radioresistance in vitro. These findings have
      important implications for our understanding of MSC functions in supporting
      allogeneic bone marrow transplantation and in tumorigenesis.

PMID- 24578292
TI  - Room temperature magnetic graphene oxide-iron oxide nanocomposite based
      magnetoresistive random access memory devices via spin-dependent trapping of
      electrons.

PMID- 24578294
TI  - Relaxin-3 stimulates the neuro-endocrine stress axis via corticotrophin-releasing
      hormone.
AB  - Relaxin-3 is a member of the insulin superfamily. It is expressed in the nucleus
      incertus of the brainstem, which has projections to the hypothalamus. Relaxin-3
      binds with high affinity to RXFP1 and RXFP3. RXFP3 is expressed within the
      hypothalamic paraventricular nucleus (PVN), an area central to the stress
      response. The physiological function of relaxin-3 is unknown but previous work
      suggests a role in appetite control, stimulation of the hypothalamic-pituitary
      gonadal axis and stress. Central administration of relaxin-3 induces c-fos
      expression in the PVN and increases plasma ACTH levels in rats. The aim of this
      study was to investigate the effect of central administration of human relaxin-3
      (H3) on the hypothalamic-pituitary-adrenal (HPA) axis in male rodents in vivo and
      in vitro. Intracerebroventricular (i.c.v) administration of H3 (5 nmol)
      significantly increased plasma corticosterone at 30 min following injection
      compared with vehicle. Intra-PVN administration of H3 (1.8-1620 pmol)
      significantly increased plasma ACTH at 1620 pmol H3 and corticosterone at 180
      1620 pmol H3 at 30 min following injection compared with vehicle. The stress
      hormone prolactin was also significantly raised at 15 min post-injection compared
      with vehicle. Treatment of hypothalamic explants with H3 (10-1000 nM) stimulated
      the release of corticotrophin-releasing hormone (CRH) and arginine vasopressin
      (AVP), but H3 had no effect on the release of ACTH from in vitro pituitary
      fragments. These results suggest that relaxin-3 may regulate the HPA axis, via
      hypothalamic CRH and AVP neurons. Relaxin-3 may act as a central signal linking
      nutritional status, reproductive function and stress.

PMID- 24578293
TI  - Leptin fails to blunt the lipopolysaccharide-induced activation of the
      hypothalamic-pituitary-adrenal axis in rats.
AB  - Obesity is a risk factor for sepsis morbidity and mortality, whereas the
      hypothalamic-pituitary-adrenal (HPA) axis plays a protective role in the body's
      defence against sepsis. Sepsis induces a profound systemic immune response and
      cytokines serve as excellent markers for sepsis as they act as mediators of the
      immune response. Evidence suggests that the adipokine leptin may play a
      pathogenic role in sepsis. Mouse endotoxaemic models present with elevated leptin
      levels and exogenously added leptin increased mortality whereas human septic
      patients have elevated circulating levels of the soluble leptin receptor (Ob-Re).
      Evidence suggests that leptin can inhibit the regulation of the HPA axis. Thus,
      leptin may suppress the HPA axis, impairing its protective role in sepsis. We
      hypothesised that leptin would attenuate the HPA axis response to sepsis. We
      investigated the direct effects of an i.p. injection of 2 mg/kg leptin on the HPA
      axis response to intraperitoneally injected 25 MUg/kg lipopolysaccharide (LPS) in
      the male Wistar rat. We found that LPS potently activated the HPA axis, as shown
      by significantly increased plasma stress hormones, ACTH and corticosterone, and
      increased plasma interleukin 1beta (IL1beta) levels, 2 h after administration.
      Pre-treatment with leptin, 2 h before LPS administration, did not influence the
      HPA axis response to LPS. In turn, LPS did not affect plasma leptin levels. Our
      findings suggest that leptin does not influence HPA function or IL1beta secretion
      in a rat model of LPS-induced sepsis, and thus that leptin is unlikely to be
      involved in the acute-phase endocrine response to bacterial infection in rats. 

PMID- 24578295
TI  - Diethylstilbestrol decreased adrenal cholesterol and corticosterone in rats.
AB  - The synthetic oestrogen diethylstilbestrol (DES), which is known to bind
      oestrogen receptors (ERs), has been reported to have adverse effects on endocrine
      homeostasis; however, the molecular mechanisms underlying these effects are
      poorly understood. In this study, we treated rats with DES and found high levels
      of this compound in the liver, adrenal glands and pituitary gland, as compared
      with other tissues. We have also detected early adverse effects of DES in the
      adrenal glands. The adrenal glands of rats treated with DES (340 MUg/kg body
      weight every 2 days) for 2 weeks showed increased weight and size and a decreased
      fat droplet size. Following 1 week of treatment with DES, the blood and adrenal
      corticosterone levels were substantially decreased without any histological
      alterations. The levels of the precursors for corticosteroid biosynthesis in the
      adrenal glands were also decreased, as determined using mass spectroscopy.
      Cholesterol, the principal material of corticosteroid biosynthesis, decreased
      substantially in the adrenal glands after only 1 week of treatment with DES. In
      conclusion, cholesterol insufficiency results in a reduction in adrenal
      corticosterone biosynthesis, which may lead to endocrine dysfunction, such as
      reproductive toxicity.

PMID- 24578296
TI  - Sexual dimorphism and thyroid dysfunction: a matter of oxidative stress?
AB  - Thyroid diseases, such as autoimmune disease and benign and malignant nodules,
      are more prevalent in women than in men, but the mechanisms involved in this sex
      difference is still poorly defined. H2O2 is produced at high levels in the
      thyroid gland and regulates parameters such as cell proliferation, migration,
      survival, and death; an imbalance in the cellular oxidant-antioxidant system in
      the thyroid may contribute to the greater incidence of thyroid disease among
      women. Recently, we demonstrated the existence of a sexual dimorphism in the
      thyrocyte redox balance, characterized by higher H2O2 production, due to higher
      NOX4 and Poldip2 expression, and weakened enzymatic antioxidant defense in the
      thyroid of adult female rats compared with male rats. In addition, 17beta
      estradiol administration increased NOX4 mRNA expression and H2O2 production in
      thyroid PCCL3 cells. In this review, we discuss the possible involvement of
      oxidative stress in estrogen-related thyroid pathophysiology. Our current
      hypothesis suggests that a redox imbalance elicited by estrogen could be involved
      in the sex differences found in the prevalence of thyroid dysfunctions.

PMID- 24578297
TI  - The wonders of 2-deoxy-D-glucose.
AB  - Through the eons of time, out of all possible configurations, nature has selected
      glucose not only as a vital source of energy to sustain life but also as the
      molecule who's structure supplies the appropriate elements required for a cell to
      grow and multiply. This understanding, at least in part, explains the profound
      effects that the analog of glucose, 2-deoxy-d-glucose, has been shown to have on
      as common and widespread diseases as cancer, viral infection, aging-related
      morbidity, epilepsy, and others. This review is confined to summarizing some of
      the salient findings of this remarkable compound as they relate mainly to cancer.

PMID- 24578298
TI  - Phase 3 efficacy and safety trial of gadobutrol, a 1.0 molar macrocyclic MR
      imaging contrast agent, in patients referred for contrast-enhanced MR imaging of
      the central nervous system.
AB  - PURPOSE: Gadobutrol is a 1.0 M macrocyclic magnetic resonance imaging (MRI)
      contrast agent. A study was performed to evaluate the efficacy and safety of
      gadobutrol-enhanced versus unenhanced imaging for central nervous system (CNS)
      lesion visualization and detection. MATERIALS AND METHODS: An international,
      multicenter, open-label, Phase III clinical trial. Patients underwent unenhanced
      and gadobutrol 1.0 M-enhanced (0.1 mmol/kg BW) MR imaging using a standardized
      protocol. Unenhanced and combined unenhanced/gadobutrol-enhanced images were
      scored by three independent, blinded readers for degree of lesion enhancement,
      border delineation, internal morphology, and total number of lesions detected
      (primary efficacy variables). Exact match of the MR diagnoses with the final
      clinical diagnosis, detection of malignant CNS lesions, and confidence in
      diagnosis were secondary efficacy variables. RESULTS: Of 343 enrolled patients,
      321 were evaluated for efficacy. All primary efficacy endpoints were met:
      superiority was demonstrated for gadobutrol-enhanced versus unenhanced MR images
      (P < 0.0001 in all cases) for lesion enhancement, border delineation, and
      internal morphology. Noninferiority was met for mean number of lesions detected.
      There were improvements in the sensitivity of malignant lesion detection, without
      a loss in specificity, exact-match diagnostic accuracy, and reader confidence.
      Treatment-related adverse events were reported in 4.1% (n = 14); all were
      nonserious. CONCLUSION: Gadobutrol 1.0M is an effective and well-tolerated
      contrast agent for CNS MRI.

PMID- 24578299
TI  - Penile rehabilitation: the evolutionary concept in the management of erectile
      dysfunction.
AB  - A compromise in erectile function is commonly experienced after radical
      prostatectomy and has been attributed to injury to vascular, neurogenic, and
      smooth muscle. The concept of rehabilitation after organ injury is not a novel
      concept and is one that has been applied to all aspects of medicine. Penile
      rehabilitation has been classically defined as the use of a device or
      pharmacologic agent to aid erectile function recovery after radical
      prostatectomy. Here we redefine penile rehabilitation as the use of any device,
      medication, or intervention to promote male sexual function as a primer before
      and after any insult to the penile erectile physiologic axis. We also review the
      epidemiology, rational and current literature on penile rehabilitation after
      prostatectomy. 

PMID- 24578300
TI  - GATA3 expression in metastatic urothelial carcinoma in fine needle aspiration
      cell blocks: a review of 25 cases.
AB  - GATA binding protein 3 is a zinc finger transcription factor with high affinity
      for urothelial tissue and is a promising immunohistochemical marker in detection
      of urothelial carcinomas (UC). We studied its usefulness in metastatic high-grade
      UC. This study was performed on cell blocks (CB) of fine needle aspirates from 25
      cases of metastatic high-grade UC in patients with previously resected high-grade
      UC. Immunohistochemical staining for GATA3, thrombomodulin, uroplakin,
      cytokeratin 7, and cytokeratin 20 was performed. Twenty-three of 25 cases of
      metastatic UC expressed GATA3 (92%); positive staining for cytokeratin 7 was
      present in 23 of 25 cases (92%), 20 of 25 (80%) stained for thrombomodulin, and
      13 of 25 (52%) stained for cytokeratin 20. No case expressed uroplakin. Five
      hundred forty-seven non-urothelial carcinomas, including breast ductal carcinoma
      (77), hepatocellular carcinoma (100), colonic adenocarcinoma (81), pancreatic
      adenocarcinoma (28), gastric adenocarcinoma (31), endometrial carcinoma (27),
      ovarian serous carcinoma (27), lung adenocarcinoma (27), lung squamous cell
      carcinoma (26), malignant melanoma (27), renal cell carcinoma (48), and prostatic
      adenocarcinoma (48) in tissue microarrays were also analyzed and were GATA3
      negative except for 35 of 77 (45.5%) of GATA3 positive breast ductal carcinoma.
      GATA3 has high sensitivity and specificity for detection of metastatic UC and
      thus may play an important role in diagnosing metastatic UC in CB samples.

PMID- 24578301
TI  - Novel NG2-CreERT2 knock-in mice demonstrate heterogeneous differentiation
      potential of NG2 glia during development.
AB  - NG2 (nerve/glia antigen-2) is a type I transmembrane glycoprotein and also known
      as chondroitin sulfate proteoglycan 4. In the parenchyma of the central nervous
      system, NG2-expressing (NG2(+) ) cells have been identified as a novel type of
      glia with a strong potential to generate oligodendrocytes (OLs) in the developing
      white matter. However, the differentiation potential of NG2 glia remained
      controversial, largely attributable to shortcomings of transgenic mouse models
      used for fate mapping. To minimize these restrictions and to more faithfully
      mimic the endogenous NG2 expression in vivo, we generated a mouse line in which
      the open reading frame of the tamoxifen-inducible form of the Cre DNA recombinase
      (CreERT2) was inserted into the NG2 locus by homologous recombination. Results
      from this novel mouse line demonstrate that at different developmental stages of
      the brain, NG2(+) cells either stayed as NG2 glia or differentiated into OLs
      during the whole life span. Interestingly, when Cre activity was induced at
      embryonic stages, a significant number of reporter(+) astrocytes could be
      detected in the gray matter after birth. However, in other brain regions, such as
      olfactory bulb, brain stem, and cerebellum, all of the NG2 glia was restricted to
      the OL lineage. In addition, tamoxifen-sensitive and NG2 gene locus-dependent
      gene recombination could be detected in a small, but persistent population of
      cortical NeuN(+) neurons starting from the second postnatal week.

PMID- 24578303
TI  - Significant RF-EMF and thermal levels observed in a computational model of a
      person with a tibial plate for grounded 40 MHz exposure.
AB  - Using numerical modeling, a worst-case scenario is considered when a person with
      a metallic implant is exposed to a radiofrequency (RF) electromagnetic field
      (EMF). An adult male standing on a conductive ground plane was exposed to a 40
      MHz vertically polarized plane wave field, close to whole-body resonance where
      maximal induced current flows are expected in the legs. A metal plate (50-300 mm
      long) was attached to the tibia in the left leg. The findings from this study re
      emphasize the need to ensure compliance with limb current reference levels for
      exposures near whole-body resonance, and not just rely on compliance with ambient
      electric (E) and magnetic (H) field reference levels. Moreover, we emphasize this
      recommendation for someone with a tibial plate, as failure to comply may result
      in significant tissue damage (increases in the localized temperature of 5-10 
      degrees C were suggested by the modeling for an incident E-field of 61.4 V/m root
      mean square (rms)). It was determined that the occupational reference level for
      limb current (100 mA rms), as stipulated in the 1998 guidelines of the
      International Commission on Non-Ionizing Radiation Protection (ICNIRP), is
      satisfied if the plane wave incident E-field levels are no more than 29.8 V/m rms
      without an implant and 23.4 V/m rms for the model with a 300 mm implant.

PMID- 24578302
TI  - Alpha-synuclein repeat variants and survival in Parkinson's disease.
AB  - OBJECTIVES: To determine whether alpha-synuclein dinucleotide repeat (REP1)
      genotypes are associated with survival in Parkinson's disease (PD). METHODS:
      Investigators from the Genetic Epidemiology of Parkinson's Disease Consortium
      provided REP1 genotypes and baseline and follow-up clinical data for cases. The
      primary outcome was time to death. Cox proportional hazards regression models
      were used to assess the association of REP1 genotypes with survival. RESULTS:
      Twenty-one sites contributed data for 6,154 cases. There was no significant
      association between alpha-synuclein REP1 genotypes and survival in PD. However,
      there was a significant association between REP1 genotypes and age at onset of PD
      (hazard ratio: 1.06; 95% confidence interval: 1.01-1.10; P value = 0.01).
      CONCLUSIONS: In our large consortium study, alpha-synuclein REP1 genotypes were
      not associated with survival in PD. Further studies of alpha-synuclein's role in
      disease progression and long-term outcomes are needed.

PMID- 24578306
TI  - Large scale thermal exfoliation and functionalization of boron nitride.

PMID- 24578304
TI  - Outcome of TCF3-PBX1 positive pediatric acute lymphoblastic leukemia patients in
      Japan: a collaborative study of Japan Association of Childhood Leukemia Study
      (JACLS) and Children's Cancer and Leukemia Study Group (CCLSG).
AB  - This study reviewed the clinical characteristics of 112 pediatric B-cell
      precursor acute lymphoblastic leukemia (BCP-ALL) patients with TCF3-PBX1 fusion
      treated according to the Japan Association of Childhood Leukemia Study (JACLS)
      ALL02 protocol (n = 82) and Children's Cancer and Leukemia Study Group (CCLSG)
      ALL 2004 protocol (n = 30). The 3-year event-free survival (EFS) and overall
      survival (OS) rates were 85.4 +/- 3.9% and 89.0 +/- 3.5% in JACLS cohort, and the
      5-year EFS and OS were 82.8 +/- 7.0% and 86.3 +/- 6.4% in CCLSG cohort,
      respectively, which are comparable to those reported in western countries.
      Conventional prognostic factors such as age at onset, initial white blood cell
      count, and National Cancer Institute risk have also no impact on OS in both
      cohorts. Surprisingly, the pattern of relapse in JACLS cohort, 9 of 82 patients,
      was unique: eight of nine patients relapsed during the maintenance phase and one
      patient had primary induction failure. However, bone marrow status and assessment
      of minimal residual disease on days 15 and 33 did not identify those patients.
      Interestingly, the two patients with IKZF1 deletion eventually relapsed in JACLS
      cohort, as did one patient in CCLSG cohort. International collaborative study of
      larger cohort is warranted to clarify the impact of the IKZF1 deletion on the
      poor outcome of TCF3-PBX1 positive BCP-ALL.

PMID- 24578305
TI  - Understanding the function of conserved variations in the catalytic loops of
      fungal glycoside hydrolase family 12.
AB  - Enzymes that cleave the xyloglucan backbone at unbranched glucose residues have
      been identified in GH families 5, 7, 12, 16, 44, and 74. Fungi produce enzymes
      that populate 20 of 22 families that are considered critical for plant biomass
      deconstruction. We searched for GH12-encoding genes in 27 Eurotiomycetes genomes.
      After analyzing 50 GH12-related sequences, the conserved variations of the amino
      acid sequences were examined. Compared to the endoglucanases, the endo
      xyloglucanase-associated YSG deletion at the negative subsites of the catalytic
      cleft with a SST insertion at the reducing end of the substrate-binding crevice
      is highly conserved. In addition, a highly conserved alanine residue was
      identified in all xyloglucan-specific enzymes, and this residue is substituted by
      arginine in more promiscuous glucanases. To understand the basis for the
      xyloglucan specificity displayed by certain GH12 enzymes, two fungal GH12
      endoglucanases were chosen for mutagenesis and functional studies: an endo
      xyloglucanase from Aspergillus clavatus (AclaXegA) and an endoglucanase from A.
      terreus (AtEglD). Comprehensive molecular docking studies and biochemical
      analyses were performed, revealing that mutations at the entrance of the
      catalytic cleft in AtEglD result in a wider binding cleft and the alteration of
      the substrate-cleavage pattern, implying that a trio of residues coordinates the
      interactions and binding to linear glycans. The loop insertion at the crevice
      reducing end of AclaXegA is critical for catalytic efficiency to hydrolyze
      xyloglucan. The understanding of the structural elements governing endo
      xyloglucanase activity on linear and branched glucans will facilitate future
      enzyme modifications with potential applications in industrial biotechnology.

PMID- 24578309
TI  - Red pericarp introgression lines derived from interspecific crosses of rice:
      physicochemical characteristics, antioxidative properties and phenolic content.
AB  - BACKGROUND: Antioxidative properties and physicochemical characteristics of
      introgression lines (ILs) and their recurrent parents were analyzed. In addition,
      catalase (CAT) and superoxide dismutase (SOD) activities and free radical
      scavenging capacity were evaluated, since these are important antioxidative
      properties for developing nutraceutical and functional foods. RESULTS:
      Comparative analysis of the brown and milled rice fractions of ILs with their
      respective recurrent parents revealed 2.26- and 1.22-fold increase in total
      phenolics, 1.95- and 2.09-fold increase in flavonoids, 8.38- and 6.80-fold
      increase in proanthocyanidins and 1.55- and 1.20-fold increase in tannins in
      brown and milled rice fractions respectively. Higher CAT (1.36- and 1.89-fold)
      and SOD (1.71- and 2.02-fold) activities and Trolox equivalent antioxidant
      capacity (TEAC, 7.13- and 1.98-fold) were observed in brown and milled rice
      fractions respectively of ILs compared with their respective recurrent parents. A
      high and positive correlation was obtained between TEAC and total phenols (0.73,
      P <= 0.01), flavonoids (0.66, P <= 0.05) and proanthocyanidins (0.69, P <= 0.05).
      The yield parameters and physicochemical characteristics of the grains, in
      general, were comparable in the ILs and their respective recurrent parents.
      CONCLUSION: The ILs of rice reported in the present study exhibited significant
      positive differences in the content of phenolic constituents and antioxidant
      properties with good grain quality characteristics over their recurrent parents,
      indicating their potential as a natural source of phytochemicals for
      nutraceutical and functional food development.

PMID- 24578310
TI  - Pilomyxoid astrocytoma of the pineal region: cytopathological features and
      differential diagnostic considerations by intraoperative smear preparation.
AB  - Pilomyxoid astrocytoma (PMA) is a recently identified type of pilocytic
      astrocytoma (PA) with shorter progression-free and overall survival, higher rate
      of recurrence, and higher risk of leptomeningeal spread compared to pilocytic
      tumors (WHO grade 2 designation). A case is presented here in which
      intraoperative imprint smears of a pineal region tumor in a 14-year-old girl
      revealed cytologic monomorphism, elongated cells with bland nuclei embedded in a
      myxoid background. The tumor cells possessed uniformly round nuclei with a smooth
      nuclear outline, fine granular chromatin, and small nucleoli. Slender cytoplasmic
      fibrillary processes and angiocentric arrangement were observed but Rosenthal
      fibers or eosinophilic granular bodies were absent. A cytologic diagnosis of PMA
      of the pineal region was suggested by intraoperative smear preparation. Histology
      and immunohistochemical results confirmed the final diagnosis. This report shows
      that smear preparation can be trustworthy for the intraoperative diagnosis of
      PMA, helping to determine the appropriate neurosurgical procedure and therapeutic
      implications.

PMID- 24578311
TI  - MRI of the carotid artery at 7 Tesla: quantitative comparison with 3 Tesla.
AB  - PURPOSE: To evaluate the 7 Tesla (T) MRI of the carotid arteries, as
      quantitatively compared with 3T. MATERIALS AND METHODS: The 7T MRI of the carotid
      arteries was performed in six healthy subjects and in two patients with carotid
      stenosis. The healthy group was scanned at 3T and at 7T, using current coil
      setups at both field strengths. T1 and T2 values of the normal carotid vessel
      wall were assessed at both field strengths. B1 (+) maps and signal to noise ratio
      (SNR) maps were obtained, as well as T1 weighted images with a resolution as high
      as 0.4 * 0.4 * 1.5 mm(3) . RESULTS: The T1 of the normal carotid vessel wall was
      found to be 1227 +/- 47 ms at 3T and 1628 +/- 130 ms at 7T, while a T2 of 55 +/-
      11 ms at 3T and 46 +/- 4 ms at 7T was found. A twofold average gain in SNR at the
      carotid arteries was found with 7T. T1 weighted images showed an increased SNR at
      7T for all subjects. CONCLUSION: Evaluation between 3T and 7T carotid MRI with
      optimized setups at both field strengths showed improved SNR at 7T, an increase
      in vessel wall T1 and a decrease in vessel wall T2.

PMID- 24578312
TI  - Remote transplantation of mesenchymal stem cells protects the heart against
      ischemia-reperfusion injury.
AB  - Cardioprotection can be evoked through extracardiac approaches. This prompted us
      to investigate whether remote transplantation of stem cells confers protection of
      the heart against ischemic injury. The cardioprotective effect of subcutaneous
      transplantation of naive versus heme oxygenase-1 (HMOX-1)-overexpressing mouse
      mesenchymal stem cells (MSC) to mice was investigated in hearts subjected to
      ischemia-reperfusion in a Langendorff perfusion system. Mice were transplanted
      into the interscapular region with naive or HMOX-1 transfected MSC isolated from
      transgenic luciferase reporter mice and compared to sham-treated animals. The
      fate of transplanted cells was followed by in vivo bioluminescence imaging,
      revealing that MSC proliferated, but did not migrate detectably from the
      injection site. Ex vivo analysis of the hearts showed that remote transplantation
      of mouse adipose-derived MSC (mASC) resulted in smaller infarcts and improved
      cardiac function after ischemia-reperfusion compared to sham-treated mice.
      Although HMOX-1 overexpression conferred cytoprotective effects on mASC against
      oxidative stress in vitro, no additive beneficial effect of HMOX-1 transfection
      was noted on the ischemic heart. Subcutaneous transplantation of MSC also
      improved left ventricular function when transplanted in vivo after myocardial
      infarction. Plasma analysis and gene expression profile of naive- and HMOX-1-mASC
      after transplantation pointed toward pentraxin 3 as a possible factor involved in
      the remote cardioprotective effect of mASC. These results have significant
      implications for understanding the behavior of stem cells after transplantation
      and development of safe and noninvasive cellular therapies with clinical
      applications. Remote transplantation of MSC can be considered as an alternative
      procedure to induce cardioprotection.

PMID- 24578313
TI  - Hypoxanthine induces oxidative stress in kidney of rats: protective effect of
      vitamins E plus C and allopurinol.
AB  - In the present study, we investigated the in vitro effect of hypoxanthine on the
      activities of antioxidant enzymes such as catalase (CAT), superoxide dismutase
      (SOD) and glutathione peroxidase, as well as on thiobarbituric-acid-reactive
      substances (TBA-RS), in the renal cortex and medulla of rats. Results showed that
      hypoxanthine, at a concentration of 10.0 MUM, enhanced the activities of CAT and
      SOD in the renal cortex of 15-, 30- and 60-day-old rats, enhanced SOD activity in
      the renal medulla of 60-day-old rats and enhanced TBA-RS levels in the renal
      medulla of 30-day-old rats, as compared with controls. Furthermore, we also
      verified the influence of allopurinol (an inhibitor of xanthine oxidase), as well
      as of the antioxidants, trolox and ascorbic acid on the effects elicited by
      hypoxanthine on the parameters tested. Allopurinol and/or administration of
      antioxidants prevented most alterations caused by hypoxanthine in the oxidative
      stress parameters evaluated. Data suggest that hypoxanthine alters antioxidant
      defences and induces lipid peroxidation in the kidney of rats; however, in the
      presence of allopurinol and antioxidants, some of these alterations in oxidative
      stress were prevented. Our findings lend support to a potential therapeutic
      strategy for this condition, which may include the use of appropriate
      antioxidants for ameliorating the damage caused by hypoxanthine.

PMID- 24578315
TI  - Quantitative evaluation of bone scintigraphy of the spinous processes of the
      equine thoracic spine at different times after administering 99mTc
      hydroxymethylene-diphosphonate.
AB  - Scintigraphic examination of the thoracic spine is well documented. However,
      there is limited information about the effects of time on image quality in the
      period following injection of radionuclide. This study aimed to determine the
      optimal time point after injection of (99m)Tc-HDP (hydroxymethylene
      diphosphonate) to achieve scintigraphic images with the best possible contrast
      and adequate count rates. Scintigraphic images of the thoracic spine of 21 horses
      were acquired two, four and six hours after administering (99m)Tc-HDP. Eight
      regions of interest were drawn in the images, four in the spinous processes and
      four in the adjacent soft tissue. The bone uptake, soft tissue uptake and the
      bone-to-soft tissue ratio were determined and compared between the different time
      points. Total count rates decreased with time after injection, but were at least
      as high as 150,000 counts per image at every time point after injection. The bone
      to-soft tissue ratio was significantly higher for the images acquired after six
      hours compared to those acquired after two and four hours (P<0.01). Delayed
      scintigraphic examinations of the spinous processes of the equine thoracic spine
      achieved images with high contrast and sufficient count rates. Therefore, the
      scintigraphic examination of the equine thoracic spine is recommended to be done
      four to six hours after injecting (99m)Tc-HDP. However, additional studies should
      be performed to determine the effect of delayed image acquisition compared to
      images taken after three hours on the detectability of lesions in other parts of
      the thoracic spine and the soft tissue. 

PMID- 24578314
TI  - Defining morbid obesity in children based on BMI 40 at age 18 using the extended
      international (IOTF) cut-offs.
AB  - BACKGROUND: Studies have reported that children who are obese are becoming more
      severely obese. OBJECTIVE: We aimed to classify obese children based on age- and
      gender-specific centile curves passing through body mass index (BMI) 30, 35 and
      40 at age 18 as 'class I', 'class II' or severe, and 'class III' or morbid
      obesity. METHODS: In addition to the International Obesity Task Force BMI cut
      offs corresponding to BMI 30 and 35, we calculated the BMI cut-offs corresponding
      to BMI 40 using the LMS method proposed by Cole and Lobstein. We classified 217
      obese children according to these criteria. RESULTS: Fifty-six (25.8%) children
      had class III obesity, 73 (33.6%) class II obesity and 88 (40.6%) class I
      obesity. Class III obese children had a higher waist circumference, systolic
      blood pressure and fasting insulinaemia compared with less obese children.
      CONCLUSION: It is clinically important to classify obese children in different
      classes of obesity severity.

PMID- 24578316
TI  - Prevalence of dog erythrocyte antigen 1.1 in galgos (Spanish greyhounds).
AB  - Dog erythrocyte antigen (DEA) 1.1 is the most clinically important blood group in
      dogs, as negative recipients for this group may develop a life-threatening acute
      haemolytic transfusion reaction if they receive several DEA 1.1 positive blood
      transfusions. Due to their physical features, galgos are frequently used as blood
      donors in clinical practice, however, there are no published data regarding the
      prevalence of DEA 1.1 in this breed. Expression of DEA 1.1 was determined in 118
      galgos and 88 dogs of other breeds being screened as potential blood donors,
      using an immunochromatographic cartridge typing kit (Quick Test DEA 1.1, Alvedia,
      Lyon, France). Of the total dogs, 53.4per cent (110/206) were positive for DEA
      1.1. The prevalence of DEA 1.1 positive blood among our population of galgos and
      other-breed dogs were 51.7 per cent (61/118) and 55.7 per cent (49/88),
      respectively. Potential risk of sensitisation in a recipient of other breed
      following non-typed blood transfusion using blood from galgos was 22.9 per cent.
      Due to the clinical significance of DEA 1.1 and the high prevalence of this blood
      group in galgos of Spain, we strongly recommend blood-typing for this group
      before administering any blood transfusion using galgos as donors, as with
      transfusions from other commonly used breeds.

PMID- 24578317
TI  - Decreased serum protein associated with Mycobacterium avium subspecies
      paratuberculosis shedding in German Holstein cows.
AB  - Using well established metabolic parameters, this study aimed to substantiate
      differences in protein and energy metabolism between Mycobacterium avium
      subspecies paratuberculosis (MAP) positive and negative dairy cows tested by
      faecal culture. A total of 227 MAP-positive and 239 MAP-negative German Holstein
      cows kept in 13 MAP-positive dairy herds were selected for metabolic testing. The
      serum concentrations of total protein (TP), bilirubin, cholesterol and
      betahydroxybutyrate were measured as well as the activities of Glutamate
      Dehydrogenase (GLDH) and Aspartate-Aminotransferase. MAP-positive cows were
      characterised by a decreased mean TP (66.5 g/l) compared to the MAP-negative
      controls (73.2 g/l). Mean log10 GLDH activities tended to be higher in MAP
      positive than MAP-negative cows. Concerning TP, there was a significant
      interaction between MAP status and farm. Within four farms, the difference
      between MAP-positive and MAP-negative animals differed significantly, while in
      the other farms this difference was not significant. It is concluded that a
      decreased TP and an increased GLDH indicate alterations in protein metabolism.
      These findings suggest an enhanced liver cell turnover in MAP-positive cows. The
      results contribute to an understanding of the metabolic alterations in MAP
      positive dairy cows. 

PMID- 24578318
TI  - Towards a therapeutic window of D2/3 occupancy for treatment of psychosis in
      Alzheimer's disease, with [18F]fallypride positron emission tomography.
AB  - OBJECTIVE: Dopamine D2/3 receptor positron emission tomography tracers have
      guided antipsychotic prescribing in young people with schizophrenia by
      establishing a 'therapeutic window' of striatal D2/3 receptor occupancy. Older
      people, particularly those with dementia, are highly susceptible to motor side
      effects and may benefit from the appropriate application of imaging techniques.
      The study aimed to adapt [18F]fallypride imaging for use in occupancy studies in
      Alzheimer's disease (AD) and to investigate whether data acquisition could be
      made more tolerable by piloting the protocol in a small sample. METHODS: Six
      participants with AD (three men; 85.0 +/- 5.6 years old; MMSE = 16.0 +/- 2.4)
      were recruited prior to commencing amisulpride for the treatment of psychosis and
      associated agitation. [18F]fallypride binding potential (BPND ) was determined
      using an interrupted scanning protocol at baseline (n = 6) and after 27.0 +/- 6.1
      days of amisulpride (25-50 mg) treatment (n = 4). D2/3 occupancy was calculated
      by percentage reduction in BPND between scanning sessions. Image data were re
      analysed after reducing individual sampling times to 20 min. RESULTS: The
      protocol was tolerated well, apart from the final (40 min) session of the post
      treatment scan in one participant. Higher occupancies were achieved in the
      striatum (caudate 47-70%, putamen 31-58%) and thalamus (54-76%) than in the
      inferior temporal gyrus (27-43%). There was high agreement between occupancy
      values derived using longer and shorter sampling times (mean absolute difference
      6.1% in the inferior temporal gyrus; <2% all other regions). CONCLUSIONS: The
      protocol is feasible for use in AD and represents the first step towards
      establishing dose-occupancy relationships across older clinical populations.

PMID- 24578319
TI  - Sulfatide-mediated control of extracellular matrix-dependent oligodendrocyte
      maturation.
AB  - In the central nervous system, the extracellular matrix (ECM) compound laminin-2,
      present on developing axons, is essential in regulating oligodendrocyte (OLG)
      maturation. For example, laminin-2 is involved in mediating interactions between
      integrins and growth factors, initially localizing in separate membrane
      microdomains. The galactosphingolipid sulfatide is an important constituent of
      these microdomains and may serve as a receptor for laminin-2. Here, we
      investigated whether sulfatide interferes with ECM-integrin interactions and, in
      this manner, modulates OLG maturation. Our data reveal that disruption of laminin
      2-sulfatide interactions impeded OLG differentiation and myelin-like membrane
      formation. On laminin-2, but not on (re)myelination-inhibiting fibronectin,
      sulfatide laterally associated with integrin alpha6 in membrane microdomains.
      Sulfatide was partly excluded from membrane microdomains on fibronectin, thereby
      likely precluding laminin-2-mediated myelination. Anti-sulfatide antibodies
      disrupted integrin alpha6-PDGFalphaR interactions on laminin-2 and induced
      demyelination in myelinated spheroid cultures, but intriguingly stimulated myelin
      like membrane formation on fibronectin. Taken together, these findings highlight
      the importance of laminin-sulfatide interactions in the formation of functional
      membrane microdomains essential for myelination. Thus, laminin-sulfatide
      interactions might control the asynchronous localized differentiation of OLGs,
      thereby allowing myelination to be triggered by axonal demand. Given the
      accumulation of fibronectin in multiple sclerosis lesions, the findings also
      provide a molecular rationale for the potential of anti-sulfatide antibodies to
      trigger quiescent endogenous OLG progenitor cells in axon remyelination. GLIA
      2014;62:927-942. 

PMID- 24578320
TI  - What is the best treatment for patients with human papillomavirus-positive and 
      negative oropharyngeal cancer?
AB  - The discovery that the human papilloma virus (HPV) is associated with a high and
      increasing percentage of oropharyngeal squamous cell carcinomas (SCCs) is among
      the most significant advances in the field of head and neck oncology. HPV
      positive oropharyngeal cancer (HPVOPC) has clinical, etiologic, pathologic, and
      molecular features that distinguish it from HPV-negative disease. Increasingly,
      HPVOPC is being diagnosed in clinical practice because of the easy availability
      of p16 immunohistochemistry, a surrogate marker of HPV. The superior prognosis of
      HPVOPC has led to a reexamination of treatment approaches, and clinical trials
      are currently investigating strategies to deintensify treatment to reduce acute
      and late toxicity while preserving efficacy. This is of particular interest in
      low-risk patients. Unfortunately, patients with HPV-negative tumors still have
      high rates of locoregional failure and more efficacious treatments are required.
      This review of oropharyngeal SCC focuses on current and investigational treatment
      strategies in patients with both HPV-positive and HPV-negative oropharyngeal SCC.

PMID- 24578321
TI  - Optical reading of contaminants in aqueous media based on gold nanoparticles.
AB  - With increasing trends of global population growth, urbanization, pollution over
      exploitation, and climate change, the safe water supply has become a global issue
      and is threatening our society in terms of sustainable development. Therefore,
      there is a growing need for a water-monitoring platform with the capability of
      rapidness, specificity, low-cost, and robustness. This review summarizes the
      recent developments in the design and application of gold nanoparticles (AuNPs)
      based optical assays to detect contaminants in aqueous media with a high
      performance. First, a brief discussion on the correlation between the optical
      reading strategy and the optical properties of AuNPs is presented. Then, we
      summarize the principle behind AuNP-based optical assays to detect different
      contaminants, such as toxic metal ion, anion, and pesticides, according to
      different optical reading strategies: colorimetry, scattering, and fluorescence.
      Finally, the comparison of these assays and the outlook of AuNP-based optical
      detection are discussed. 

PMID- 24578322
TI  - Concept of double salt fortification; a tool to curtail micronutrient
      deficiencies and improve human health status.
AB  - Fortification of food with micronutrients such as vitamins and minerals is one of
      the main strategies used to combat micronutrient deficiencies. Fortification in
      common salt is a fruitful strategy because of the daily consumption of 5-12 g
      salt per person globally. Therefore double fortification of salt with iodine and
      iron could be a reasonable approach to prevent both iodine and iron deficiencies.
      It is reckoned that about two billion people are iodine-deficient worldwide.
      Iodine deficiency during pregnancy may affect the health status of both mother
      and fetus and increase infant mortality. Deficiencies of both these
      micronutrients during childhood affect somatic growth and cognitive and
      neurological function. Thyroid metabolism is negatively affected by iron
      deficiency and reduced effectiveness of iodine prophylaxis in areas of endemic
      goiter. High prevalence of iron deficiency among children may be reduced by the
      application of effective iodized salt programs. However, ensuring the stability
      and bioavailability of both iron and iodine as double-fortified salt is
      difficult. Iodine present in iodide or iodate form in dual-fortified salt is
      oxidized to free iodine in the presence of ferrous ions and oxygen and
      consequently loses its characteristics. Moreover, ferrous iron is more
      bioavailable but is readily oxidized to the less bioavailable ferric form.
      However, both forms of iron may lead to discoloration of the final product, which
      can be reduced by providing a physical barrier around the iron. Salt
      encapsulation is one of the best tools to provide a physical barrier for
      undesirable reactions and interactions during storage. In this review the concept
      of dual salt fortification, the impact of fortification on curing various life
      threatening maladies, latest assessments of mineral deficiencies and the choice
      of fortificants are discussed.

PMID- 24578323
TI  - Pseudosarcomatous proliferative myositis of the sternocleidomastoid: a case
      report.

PMID- 24578324
TI  - Fast computation of myelin maps from MRI T2 relaxation data using multicore CPU
      and graphics card parallelization.
AB  - PURPOSE: To develop a fast algorithm for computing myelin maps from multiecho T2
      relaxation data using parallel computation with multicore CPUs and graphics
      processing units (GPUs). MATERIALS AND METHODS: Using an existing MATLAB
      (MathWorks, Natick, MA) implementation with basic (nonalgorithm-specific)
      parallelism as a guide, we developed a new version to perform the same
      computations but using C++ to optimize the hybrid utilization of multicore CPUs
      and GPUs, based on experimentation to determine which algorithmic components
      would benefit from CPU versus GPU parallelization. Using 32-echo T2 data of
      dimensions 256 * 256 * 7 from 17 multiple sclerosis patients and 18 healthy
      subjects, we compared the two methods in terms of speed, myelin values, and the
      ability to distinguish between the two patient groups using Student's t-tests.
      RESULTS: The new method was faster than the MATLAB implementation by 4.13 times
      for computing a single map and 14.36 times for batch-processing 10 scans. The two
      methods produced very similar myelin values, with small and explainable
      differences that did not impact the ability to distinguish the two patient
      groups. CONCLUSION: The proposed hybrid multicore approach represents a more
      efficient alternative to MATLAB, especially for large-scale batch processing.

PMID- 24578325
TI  - Abuse of older persons with dementia by family caregivers: results of a 6-month
      prospective study in Hong Kong.
AB  - OBJECTIVE: To examine the association between care recipients' agitated
      behaviors, family caregivers' burnout, and abuse in community dwelling older
      Chinese with dementia in Hong Kong. DESIGN: This was a 6-month prospective study.
      METHOD: One hundred forty-nine caregivers provided information on their
      demographic characteristics, care recipients' everyday functioning and agitated
      behaviors, and caregivers' burnout symptoms. Caregivers were re-interviewed 6
      months later and provided information on changes in both care recipients'
      everyday functioning and agitated behaviors, and verbally and physically abusive
      behaviors directed at care recipients in the past month. RESULTS: The single most
      significant variable in predicting abuse at 6-month follow-up was abuse at
      baseline. In addition, verbal abuse was predicted by more co-residing days, a
      high level of agitated behavior, and a strong sense of caregiver
      depersonalization. Care recipients were more likely to be physically abused if
      they were male, had no chronic conditions other than dementia, and demonstrated a
      high level of agitated behaviors. Entering caregiver burnout into the model did
      not modify the association between care recipients' agitated behavior and abuse
      for either verbal or physical abuse. CONCLUSION: This study is the first to
      establish an association between care recipients' agitated behaviors, burnout,
      and abuse by family caregivers using prospective data. The present results
      confirmed that care recipients' agitated behaviors and caregivers' symptoms of
      burnout are associated with family caregivers' abusive behaviors. Caregiver
      burnout did not mediate the association between agitated behaviors and abuse.
      Proper management of care recipients' agitated behaviors and adequate support
      provided to family caregivers may help prevent the development of new cases of
      elder mistreatment.

PMID- 24578326
TI  - An unusual case of hematuria.

PMID- 24578327
TI  - BMP signaling regulates the tempo of adult hippocampal progenitor maturation at
      multiple stages of the lineage.
AB  - Novel environmental stimuli, such as running and learning, increase proliferation
      of adult hippocampal neural stem cells (NSCs) and enlarge the population of new
      neurons. However, it remains unclear how increased numbers of new neurons can be
      generated in a time frame far shorter than the time required for proliferating
      stem cells to generate these neurons. Here, we show that bone morphogenetic
      protein (BMP) signaling in the subgranular zone regulates the tempo of neural
      progenitor cell (NPC) maturation by directing their transition between states of
      quiescence and activation at multiple stages along the lineage. Virally mediated
      overexpression of BMP4 caused NPC cell cycle exit and slowed the normal
      maturation of NPCs, resulting in a long-term reduction in neurogenesis.
      Conversely, overexpression of the BMP inhibitor noggin promoted NPC cell cycle
      entry and accelerated NPC maturation. Similarly, BMP receptor type 2 (BMPRII)
      ablation in Ascl1(+) intermediate NPCs accelerated their maturation into neurons.
      Importantly, ablation of BMPRII in GFAP(+) stem cells accelerated maturation
      without depleting the NSC pool, indicating that an increased rate of neurogenesis
      does not necessarily diminish the stem cell population. Thus, inhibition of BMP
      signaling is a mechanism for rapidly expanding the pool of new neurons in the
      adult hippocampus by tipping the balance between quiescence/activation of NPCs
      and accelerating the rate at which they mature into neurons.

PMID- 24578328
TI  - Analysis of proteins showing differential changes during ATP oscillations in
      chondrogenesis.
AB  - Prechondrogenic condensation is a critical step for skeletal pattern formation.
      Our previous study showed that ATP oscillations play an essential role in
      prechondrogenic condensation because they induce oscillatory secretion. However,
      the molecular mechanisms that underlie ATP oscillations remain poorly understood.
      We examined how differential changes in proteins are implicated in ATP
      oscillations during chondrogenesis by using liquid chromatography/mass
      spectrometry. Our analysis showed that a number of proteins involved in ATP
      synthesis/consumption, catabolic/anabolic processes, actin dynamics, cell
      migration and adhesion were detected at either the peak or the trough of ATP
      oscillations, which implies that these proteins have oscillatory expression
      patterns that are coupled to ATP oscillations. On the basis of the results, we
      suggest that (1) the oscillatory expression of proteins involved in ATP
      synthesis/consumption and catabolic/anabolic processes can contribute to the
      generation or maintenance of ATP oscillations and that (2) the oscillatory
      expression of proteins involved in actin dynamics, cell migration and adhesion
      plays key roles in prechondrogenic condensation by inducing collective adhesion
      and migration in cooperation with ATP oscillations.

PMID- 24578329
TI  - Predictors of treatment outcomes in ANCA-associated vasculitis with severe kidney
      failure.
AB  - BACKGROUND AND OBJECTIVES: In ANCA-associated GN, severe renal dysfunction
      portends a poor prognosis for renal recovery and patient survival. This study
      evaluated the prognostic factors affecting renal and patient outcomes in patients
      presenting with severe kidney failure to guide immunosuppressive therapy. DESIGN,
      SETTING, PARTICIPANTS, & MEASUREMENTS: This study retrospectively evaluated
      clinical and histopathologic characteristics of 155 patients who underwent biopsy
      between October 1985 and February 2011 (median eGFR at presentation, 7.1 ml/min
      per 1.73 m(2); 87% required hemodialysis), all treated with immunosuppressive
      medications. Three outcomes of interest were measured: patient survival, renal
      survival, and treatment response (defined as dialysis-free survival without
      active vasculitis by 4 months after biopsy). Competing risk, Cox, and logistic
      regression analyses were conducted for each outcome measure. RESULTS: Within 4
      months after biopsy, treatment response was attained in 51% of patients, 35%
      remained on dialysis, and 14% died. In a competing risk analysis, estimated
      cumulative incidence rates of ESRD and disease-related mortality were 26% and 17%
      at 1 year and 32% and 28% at 5 years, respectively. Cyclophosphamide therapy and
      treatment response by 4 months were independently associated with patient and
      renal survival, adjusting for the percentage of normal glomeruli, histopathologic
      chronicity index score, and baseline clinical characteristics. Only 5% of
      patients still dialysis dependent at 4 months subsequently recovered renal
      function. Low chronicity index score (odds ratio [OR], 1.16; 95% confidence
      interval [95% CI], 1.04 to 1.30, per unit decrease) and baseline eGFR>10 ml/min
      per 1.73 m(2) (OR, 2.77; 95% CI, 1.09 to 7.01) were significantly associated with
      treatment response by 4 months. Among cyclophosphamide-treated patients, the
      likelihood of treatment response was >14% even with highest chronicity index
      score and eGFR<10 ml/min per 1.73 m(2). CONCLUSIONS: Although low baseline renal
      function and severe renal scarring are associated with lower treatment response
      rate, no "futility" threshold could be identified. Conversely, continued
      immunosuppressive therapy beyond 4 months is unlikely to benefit patients who
      remain dialysis dependent.

PMID- 24578330
TI  - American Society of Nephrology quiz and questionnaire 2013: glomerulonephritis.
AB  - The Nephrology Quiz and Questionnaire (NQ&Q) remains an extremely popular session
      for attendees of the Annual Meeting of the American Society of Nephrology. As in
      past years, the conference hall of the 2013 meeting was overflowing with
      interested audience members. Topics covered by expert discussants included
      electrolyte and acid-base disorders, glomerular disease, ESRD/dialysis, and
      transplantation. Complex cases representing each of these categories, along with
      single best answer questions, were prepared by a panel of experts. Before the
      meeting, program directors of United States nephrology training programs answered
      questions through an Internet-based questionnaire. A new addition to the NQ&Q was
      participation in the questionnaire by nephrology fellows. To review the process,
      members of the audience test their knowledge and judgment on a series of case
      oriented questions prepared and discussed by experts. Their answers are compared
      in real time using audience response devices with the answers of nephrology
      fellows and training program directors. The correct and incorrect answers are
      then briefly discussed after the audience responses and the results of the
      questionnaire are displayed. This article recapitulates the session and
      reproduces its educational value for CJASN readers. Enjoy the clinical cases and
      expert discussions. 

PMID- 24578331
TI  - Association of C4d deposition with clinical outcomes in IgA nephropathy.
AB  - BACKGROUND AND OBJECTIVES: Several studies have suggested that activation of the
      complement system is a contributing pathogenic mechanism in IgA nephropathy
      (IgAN). C4d staining is an inexpensive and easy-to-perform method for the
      analysis of renal biopsies. This study aimed to assess the clinical and
      prognostic implications of C4d staining in IgAN. DESIGN, SETTING, PARTICIPANTS, &
      MEASUREMENTS: This retrospective cohort study included 283 patients with IgAN in
      11 hospitals in Spain who underwent a renal biopsy between 1979 and 2010. The
      primary predictor was mesangial C4d staining. Secondary predictors included
      demographic, clinical, and laboratory characteristics, and Oxford pathologic
      classification criteria. The primary end point was the cumulative percentage of
      patients who developed ESRD, defined as onset of chronic dialysis or renal
      transplantation. C4d was analyzed by immunohistochemical staining using a
      polyclonal antibody. Kaplan-Meier and Cox proportional hazards analyses were
      performed to evaluate the effect of C4d staining on renal survival. RESULTS:
      There were 109 patients (38.5%) and 174 patients (61.5%) who were classified as
      C4d positive and C4d negative, respectively. Renal survival at 20 years was 28%
      in C4d-positive patients versus 85% in C4d-negative patients (P<0.001).
      Independent risk factors associated with ESRD were as follows: proteinuria
      (hazard ratio [HR] per every 1 g/d increase. 1.16; 95% confidence interval [95%
      CI], 1.03 to 1.31; P=0.01), eGFR (HR per every 1 ml/min per 1.73 m(2) increase,
      0.96; 95% CI, 0.94 to 0.97; P<0.001), T2 Oxford classification (tubular
      atrophy/interstitial fibrosis, >50%; HR, 4.42; 95% CI, 1.40 to 13.88; P=0.01),
      and C4d-positive staining (HR, 2.45; 95% CI, 1.30 to 4.64; P=0.01). CONCLUSIONS:
      C4d-positive staining is an independent risk factor for the development of ESRD
      in IgAN. This finding is consistent with the possibility that complement
      activation is involved in the pathogenesis of this disease.

PMID- 24578333
TI  - Association of low-protein supplemented diets with fetal growth in pregnant women
      with CKD.
AB  - BACKGROUND AND OBJECTIVES: Women affected by CKD increasingly choose to get
      pregnant. Experience with low-protein diets is limited. The aim of this study was
      to review results obtained from pregnant women with CKD on supplemented vegan
      vegetarian low-protein diets. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This
      was a single-arm, open intervention study between 2000-2012 of a low-protein diet
      in pregnant patients with stages 3-5 CKD or severe proteinuria (>1 g/d in the
      first trimester or nephrotic at any time). Stages 3-5 CKD patients who were not
      on low-protein diets for clinical, psychologic, or logistic reasons served as
      controls. The setting was the Obstetrics-Nephrology Unit dedicated to kidney
      diseases in pregnancy. The treated group included 24 pregnancies--21 singleton
      deliveries, 1 twin pregnancy, 1 abortion, and 1 miscarriage. Additionally, there
      were 21 controls (16 singleton deliveries, 5 miscarriages). The diet was a vegan
      vegetarian low-protein diet (0.6-0.8 g/kg per day) with keto-acid supplementation
      and 1-3 protein-unrestricted meals allowed per week. RESULTS: Treated patients
      and controls were comparable at baseline for median age (35 versus 34 years),
      referral week (7 versus 8), eGFR (59 versus 54 ml/min), and hypertension (43.5%
      versus 33.3%); median proteinuria was higher in patients on the low-protein diet
      (1.96 [0.1-6.3] versus 0.3 [0.1-2.0] g/d; P<0.001). No significant differences
      were observed in singletons with regard to gestational week (34 versus 36) or
      Caesarean sections (76.2% versus 50%). Kidney function at delivery was not
      different, but proteinuria was higher in the diet group. Incidence of small for
      gestational age babies was significantly lower in the diet group (3/21) versus
      controls (7/16; chi-squared test; P=0.05). Throughout follow-up (6 months to 10
      years), hospitalization rates and prevalence of children below the third
      percentile were similar in both groups. CONCLUSION: Vegan-vegetarian supplemented
      low-protein diets in pregnant women with stages 3-5 CKD may reduce the likelihood
      of small for gestational age babies without detrimental effects on kidney
      function or proteinuria in the mother.

PMID- 24578332
TI  - Presence and outcomes of kidney disease in patients with pulmonary hypertension.
AB  - BACKGROUND AND OBJECTIVES: Pulmonary hypertension is associated with higher
      mortality rates. The associations of nondialysis-dependent CKD and all-cause
      mortality in patients with pulmonary hypertension were studied. DESIGN, SETTING,
      PARTICIPANTS, & MEASUREMENTS: The study population included those patients who
      underwent right heart catheterization for confirmation of pulmonary hypertension
      between 1996 and January 2011. Pulmonary hypertension was defined as the presence
      of mean pulmonary artery pressure >= 25 mmHg at rest measured by right heart
      catheterization. CKD was defined as the presence of two measurements of eGFR<60
      ml/min per 1.73 m(2) 90 days apart. The risk factors associated with CKD as well
      as the association between CKD and death in those patients with pulmonary
      hypertension using logistic regression and Cox proportional hazard models were
      examined. RESULTS: Of 1088 patients with pulmonary hypertension, 388 (36%)
      patients had CKD: 340 patients had stage 3 CKD, and 48 (4%) patients had stage 4
      CKD. In the multivariable analysis, older age, higher hemoglobin, and higher mean
      right atrial pressures were independently associated with CKD. During a median
      follow-up of 3.2 years (interquartile range=1.5-5.6 years), 559 patients died.
      After adjusting for relevant covariates, presence of stage 3 CKD (hazard ratio,
      1.37; 95% confidence interval, 1.14 to 1.66) and stage 4 CKD (hazard ratio, 2.69;
      95% confidence interval, 1.88 to 3.86) was associated with all-cause mortality in
      those patients with pulmonary hypertension. When eGFR was examined as a
      continuous measure, a 5 ml/min per 1.73 m(2) lower eGFR was associated with a 5%
      (95% confidence interval, 1.03 to 1.07) higher hazard for death. This higher risk
      with CKD was similar irrespective of demographics, left ventricular function, and
      pulmonary capillary wedge pressure. CONCLUSION: In a clinical population referred
      for right heart catheterization, presence of CKD was associated with higher all
      cause mortality in those patients with pulmonary hypertension. Mechanisms that
      may underlie these associations warrant additional studies.

PMID- 24578334
TI  - Validation of the Kidney Disease Improving Global Outcomes criteria for AKI and
      comparison of three criteria in hospitalized patients.
AB  - BACKGROUND AND OBJECTIVES: AKI is a major clinical problem and predictor of
      outcome in hospitalized patients. In 2013, the Kidney Disease: Improving Global
      Outcomes (KDIGO) group published the third consensus AKI definition and
      classification system after the Risk, Injury, Failure, Loss of Kidney Function,
      and End-Stage Kidney Disease (RIFLE) and the Acute Kidney Injury Network (AKIN)
      working group systems. It is unclear which system achieves optimal
      prognostication in hospital patients. DESIGN, SETTING, PARTICIPANTS, &
      MEASUREMENTS: A retrospective observational study using hospital laboratory,
      admission, and discharge databases was performed that included adult patients
      admitted to a teaching hospital in Tokyo, Japan between April 1, 2008, and
      October 31, 2011. AKI occurring during each hospital stay was identified, and
      discriminative ability of each AKI classification system based on serum
      creatinine for the prediction of hospital mortality was assessed. The receiver
      operating characteristic curve, a graphical measure of test performance, and the
      area under the curve were used to evaluate how classifications preformed on the
      study population. RESULTS: In total, 49,518 admissions were studied, of which
      11.0% were diagnosed with RIFLE criteria and 11.6% were diagnosed with KDIGO
      criteria, but only 4.8% were diagnosed with AKIN criteria. Overall hospital
      mortality was 3.0%. AKI staging and hospital mortality were closely correlated in
      all systems. Discrimination for hospital mortality was similar for RIFLE and
      KDIGO criteria (area under the curve=0.77 versus 0.78; P=0.02), whereas AKIN
      discrimination was inferior (area under the curve=0.69 versus RIFLE [P<0.001]
      versus KDIGO [P<0.001]). CONCLUSION: Among hospital patients, KDIGO and RIFLE
      criteria achieved similar discrimination, but the discrimination of AKIN was
      inferior.

PMID- 24578335
TI  - Heritability of urinary traits that contribute to nephrolithiasis.
AB  - BACKGROUND AND OBJECTIVES: Kidney stones and their risk factors aggregate in
      families, yet few studies have systematically estimated heritabilities and
      genetic correlations of the numerous urinary traits associated with risk of
      kidney stones. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Twenty-four-hour
      urine samples were collected from the Genetic Epidemiology Network of
      Arteriopathy cohort of families in Rochester, Minnesota, to measure urinary
      determinants of supersaturation. Diet was assessed using the Viocare food
      frequency questionnaire. Heritabilities and genetic correlations among the
      urinary traits were estimated using variance components methods. RESULTS: Samples
      were available from 811 individuals (344 men, 467 women; mean age 66 +/- 9
      years). Age, sex, and weight were significantly correlated with the majority of
      urinary traits. Many urine excretions (calcium, magnesium, citrate excretion) had
      strong evidence for heritability (P<0.01) both before and after adjusting for the
      identified covariates. Among significantly heritable urinary traits, genetic
      factors explained 20%-36% of interindividual variation after adjustment for
      covariates. Urinary calcium excretion was significantly genetically correlated
      with urinary magnesium and with urinary citrate excretion (P<0.05). Although eGFR
      influenced many urinary traits, controlling for eGFR did not greatly affect
      estimated heritabilities. CONCLUSIONS: Evidence from this cohort suggests a
      strong heritable component to many urinary nephrolithiasis risk factors. Further
      study of genetic influences on urinary traits relevant for kidney stone
      pathogenesis is warranted.

PMID- 24578338
TI  - One-step transfer and integration of multifunctionality in CVD graphene by
      TiO2/graphene oxide hybrid layer.
AB  - We present a straightforward method for simultaneously enhancing the electrical
      conductivity, environmental stability, and photocatalytic properties of graphene
      films through one-step transfer of CVD graphene and integration by introducing
      TiO2/graphene oxide layer. A highly durable and flexible TiO2 layer is
      successfully used as a supporting layer for graphene transfer instead of the
      commonly used PMMA. Transferred graphene/TiO2 film is directly used for measuring
      the carrier transport and optoelectronic properties without an extra TiO2 removal
      and following deposition steps for multifunctional integration into devices
      because the thin TiO2 layer is optically transparent and electrically
      semiconducting. Moreover, the TiO2 layer induces charge screening by
      electrostatically interacting with the residual oxygen moieties on graphene,
      which are charge scattering centers, resulting in a reduced current hysteresis.
      Adsorption of water and other chemical molecules onto the graphene surface is
      also prevented by the passivating TiO2 layer, resulting in the long term
      environmental stability of the graphene under high temperature and humidity. In
      addition, the graphene/TiO2 film shows effectively enhanced photocatalytic
      properties because of the increase in the transport efficiency of the
      photogenerated electrons due to the decrease in the injection barrier formed at
      the interface between the F-doped tin oxide and TiO2 layers.

PMID- 24578337
TI  - Bisphosphonates and mortality in women with CKD and the presence or absence of
      cardiovascular disease.
AB  - BACKGROUND AND OBJECTIVES: A modest protective association between bisphosphonate
      prescription and mortality among women with CKD but without clinically manifest
      cardiovascular disease has been shown. Whether a prior cardiovascular event
      (myocardial infarction, stroke, or heart failure) modifies this association is
      unknown. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A cohort of adult women
      with stages 3 and 4 CKD receiving primary care in a rural integrated health care
      system during the period 2004-2011 without history of advanced malignancy or
      organ transplantation (n=6756, median age=74 years, median follow-up=4.3 years)
      was retrospectively assembled. The primary analysis compared those patients
      prescribed bisphosphonates (both prevalent and incident use during follow-up)
      with those patients not prescribed. Additional approaches were taken to account
      for survival and indication biases. The primary outcome was time to death by Cox
      multivariable regression. RESULTS: In the primary analysis, compared with women
      not prescribed a bisphosphonate, the hazard ratio (95% confidence interval) for
      death among women prescribed a bisphosphonate was 0.90 (0.78 to 1.04) if there
      was no history of cardiovascular event but 1.22 (1.04 to 1.42) if there was
      history of cardiovascular event (P for interaction=0.004). In the additional
      approaches, associations between bisphosphonate prescription and mortality among
      those patients with a prior cardiovascular history varied: hazard ratios (95%
      confidence intervals) were 1.25 (1.01 to 1.57), 1.48 (1.16 to 1.88), and 0.94
      (0.66 to 1.34). Interaction by prior cardiovascular event history varied across
      these three approaches (P=0.07, P=0.22, and P=0.05). CONCLUSION: In this study of
      women with CKD, the association between bisphosphonate treatment and mortality
      risk was inconclusive across a series of analyses designed to account for various
      types of selection and indication bias.

PMID- 24578339
TI  - Basal CD38/cyclic ADP-ribose-dependent signaling mediates ATP release and
      survival of microglia by modulating connexin 43 hemichannels.
AB  - It is necessary to investigate the mechanisms underlying ATP release from neural
      cells, because extracellular ATP plays multiple important biological roles in the
      brain. CD38 is an ectoenzyme that consumes NAD(+) to produce cyclic ADP-ribose
      (cADPR), a potent agonist of ryanodine receptors. Our previous study showed that
      CD38 reductions led to microglial apoptosis. In this study, we used both murine
      microglial BV2 cells and primary microglial cultures as cellular models to test
      our hypothesis that basal CD38/cyclic ADP-ribose (CD38/cADPR)-dependent signaling
      plays a key role in ATP release, which mediates basal survival of microglia. We
      found that inhibition of CD38/cADPR-dependent signaling by CD38 silencing or 8
      Bromo-cADPR, a ryanodine receptor antagonist, produced significant ATP release
      from BV2 microglia. Cx43 small interfering RNA and Cx43 hemichannel blocker 18
      alpha-glycyrrhetinic acid completely prevented the CD38 silencing or 8-Bromo
      cADPR-induced ATP release. Prevention of the ATP release could also be due to
      P2X7 receptor antagonists. Our study has further suggested a key role of ATP
      release in the microglial apoptosis induced by decreased CD38/cADPR-dependent
      signaling. In addition, by using primary microglial cultures, we found that 8
      Bromo-cADPR also induced significant ATP release, which could be attenuated by 18
      alpha-glycyrrhetinic acid. 8-Bromo-cADPR was also found to induce death of
      primary microglial cultures. In conclusion, our results have suggested novel
      roles of basal activation of CD38/cADPR-dependent signaling in mediating
      microglial functions and survival: It mediates ATP release from microglia by
      modulating Cx43 hemichannels, which can significantly affect microglial survival.

PMID- 24578336
TI  - The use of fibroblast growth factor 23 testing in patients with kidney disease.
AB  - The emergence of fibroblast growth factor 23 as a potentially modifiable risk
      factor in CKD has led to growing interest in its measurement as a tool to assess
      patient risk and target therapy. This review discusses the analytical and
      clinical challenges faced in translating fibroblast growth factor 23 testing into
      routine practice. As for other bone mineral markers, agreement between commercial
      fibroblast growth factor 23 assays is poor, mainly because of differences in
      calibration, but also, these differences reflect the variable detection of
      hormone fragments. Direct comparison of readout from different assays is
      consequently limited and likely hampers setting uniform fibroblast growth factor
      23-directed targets. Efforts are needed to standardize assay output to enhance
      clinical use. Fibroblast growth factor 23 is robustly associated with
      cardiovascular and renal outcomes in patients with CKD and adds value to risk
      assessments based on conventional risk factors. Compared with most other mineral
      markers, fibroblast growth factor 23 shows better intraindividual temporal
      stability, with minimal diurnal and week-to-week variability, but substantial
      interindividual variation, maximizing discriminative power for risk
      stratification. Conventional therapeutic interventions for the CKD-mineral bone
      disorder, such as dietary phosphate restriction and use of oral phosphate binders
      or calcimimetics, are associated with variable efficacy at modulating circulating
      fibroblast growth factor 23 concentrations, like they are for other mineral
      metabolites. Dual therapy with dietary phosphate restriction and noncalcium-based
      binder use achieves the most consistent fibroblast growth factor 23-lowering
      effect and seems best monitored using an intact assay. Additional studies are
      needed to evaluate whether strategies aimed at reducing levels or antagonizing
      its action have beneficial effects on clinical outcomes in CKD patients.
      Moreover, a better understanding of the mechanisms driving fibroblast growth
      factor 23 elevations in CKD is needed to inform the use of therapeutic
      interventions targeting fibroblast growth factor 23 excess. This evidence must be
      forthcoming to support the use of fibroblast growth factor 23 measurement and
      fibroblast growth factor 23-directed therapy in the clinic.

PMID- 24578340
TI  - Myosin IIB and F-actin control apical vacuolar morphology and histamine-induced
      trafficking of H-K-ATPase-containing tubulovesicles in gastric parietal cells.
AB  - Selective inhibitors of myosin or actin function and confocal microscopy were
      used to test the role of an actomyosin complex in controlling morphology,
      trafficking, and fusion of tubulovesicles (TV) containing H-K-ATPase with the
      apical secretory canaliculus (ASC) of primary-cultured rabbit gastric parietal
      cells. In resting cells, myosin IIB and IIC, ezrin, and F-actin were associated
      with ASC, whereas H-K-ATPase localized to intracellular TV. Histamine caused
      fusion of TV with ASC and subsequent expansion resulting from HCl and water
      secretion; F-actin and ezrin remained associated with ASC whereas myosin IIB and
      IIC appeared to dissociate from ASC and relocalize to the cytoplasm. ML-7
      (inhibits myosin light chain kinase) caused ASC of resting cells to collapse and
      most myosin IIB, F-actin, and ezrin to dissociate from ASC. TV were unaffected by
      ML-7. Jasplakinolide (stabilizes F-actin) caused ASC to develop large blebs to
      which actin, myosin II, and ezrin, as well as tubulin, were prominently
      localized. When added prior to stimulation, ML-7 and jasplakinolide prevented
      normal histamine-stimulated transformations of ASC/TV and the cytoskeleton, but
      they did not affect cells that had been previously stimulated with histamine.
      These results indicate that dynamic pools of actomyosin are required for
      maintenance of ASC structure in resting cells and for trafficking of TV to ASC
      during histamine stimulation. However, the dynamic pools of actomyosin are not
      required once the histamine-stimulated transformation of TV/ASC and cytoskeleton
      has occurred. These results also show that vesicle trafficking in parietal cells
      shares mechanisms with similar processes in renal collecting duct cells, neuronal
      synapses, and skeletal muscle.

PMID- 24578343
TI  - IL-4 induces columnar-like differentiation of esophageal squamous epithelium
      through JAK/PI3K pathway: possible role in pathogenesis of Barrett's esophagus.
AB  - Barrett's esophagus is characterized by a distinct Th2-predominant cytokine
      profile (IL-4) from in vivo or ex vivo evidence. The detailed role of cytokines
      in Barrett's esophagus, particularly whether Th2 cytokines are causative factors
      driving metaplastic processes, remains unknown. In this study, air-liquid
      interface-cultured human esophageal epithelial cells were stimulated by a Th2
      cytokine, IL-4, and Th1 cytokines, TNF-alpha and IL-1beta, continuously for 10
      days. Barrier function was determined by transepithelial electrical resistance.
      Morphological changes were investigated by hematoxylin and eosin staining.
      Keratin profile (keratin 7, 8, 13, and 14) and squamous differentiation markers
      (involucrin) were investigated by RT-quantitative PCR, Western blotting, and
      immunohistochemical staining. Pharmacological inhibitors were used to identify
      the underlying cellular signaling. We report that IL-4, TNF-alpha, and IL-1beta
      decrease barrier function, but only IL-4 significantly increases cell layers and
      changes cell morphology. IL-4 time dependently downregulates the expression
      levels of the squamous cell markers involucrin and keratin 13 and upregulates the
      expression levels of the columnar cell markers keratin 7 and 8. Neither TNF-alpha
      nor IL-1beta shows any effect on these indexes. JAK inhibitor I and PI3K
      inhibitors significantly block the IL-4-induced changes in the levels of keratin
      8 and 13. In conclusion, IL-4 inhibits squamous differentiation program of
      esophageal epithelial cells and induces differentiation toward columnar cells
      through the JAK/PI3K pathway. Thus IL-4 may be involved in the early stages of
      Barrett's esophagus development.

PMID- 24578341
TI  - Feeding-dependent activation of enteric cells and sensory neurons by lymphatic
      fluid: evidence for a neurolymphocrine system.
AB  - Lymphatic fluid is a plasma filtrate that can be viewed as having biological
      activity through the passive accumulation of molecules from the interstitial
      fluid. The possibility that lymphatic fluid is part of an active self-contained
      signaling process that parallels the endocrine system, through the activation of
      G-protein coupled receptors (GPCR), has remained unexplored. We show that the
      GPCR lysophosphatidic acid 5 (LPA5) is found in sensory nerve fibers expressing
      calcitonin gene-related peptide (CGRP) that innervate the lumen of lymphatic
      lacteals and enteric nerves. Using LPA5 as a model for nutrient-responsive GPCRs
      present on sensory nerves, we demonstrate that dietary protein hydrolysate
      (peptone) can induce c-Fos expression in enterocytes and nerves that express
      LPA5. Mesenteric lymphatic fluid (MLF) mobilizes intracellular calcium in cell
      models expressing LPA5 upon feeding in a time- and dose-dependent manner. Primary
      cultured neurons of the dorsal root ganglia expressing CGRP are activated by MLF,
      which is enhanced upon LPA5 overexpression. Activation is independent of the
      known LPA5 agonists, lysophosphatidic acid and farnesyl pyrophosphate. These data
      bring forth a pathway for the direct stimulation of sensory nerves by luminal
      contents and interstitial fluid. Thus, by activating LPA5 on sensory nerves, MLF
      provides a means for known and yet to be identified constituents of the
      interstitial fluid to act as signals to comprise a "neurolymphocrine" system.

PMID- 24578342
TI  - Inhibition of Galphai activity by Gbetagamma is mediated by PI 3-kinase-gamma-
      and cSrc-dependent tyrosine phosphorylation of Galphai and recruitment of RGS12.
AB  - Others and we have characterized several Gbetagamma-dependent effectors in smooth
      muscle, including G protein-coupled receptor kinase 2 (GRK2), PLCbeta3, and
      phosphatidylinositol (PI) 3-kinase-gamma, and have identified various signaling
      targets downstream of PI 3-kinase-gamma, including cSrc, integrin-linked kinase,
      and Rac1-Cdc42/p21-activated kinase/p38 MAP kinase. This study identified a novel
      mechanism whereby Gbetagamma acting via PI 3-kinase-gamma and cSrc exerts an
      inhibitory influence on Galphai activity. The Gi2-coupled delta-opioid receptor
      agonist d-penicillamine (2,5)-enkephalin (DPDPE) activated cSrc, stimulated
      tyrosine phosphorylation of Galphai2, and induced regulator of G protein
      signaling 12 (RGS12) association; all three events were blocked by PI 3-kinase
      (LY294002) and cSrc (PP2) inhibitors and by expression of the COOH-terminal
      sequence of GRK2-(495-689), a Gbetagamma-scavenging peptide. Inhibition of
      forskolin-stimulated cAMP and muscle relaxation by DPDPE was augmented by PP2,
      LY294002, and a selective PI 3-kinase-gamma inhibitor, AS-605420. Expression of
      tyrosine-deficient (Y69F, Y231F, or Y321F) Galphai2 mutant or knockdown of RGS12
      blocked Galphai2 phosphorylation and Galphai2-RGS12 association and caused
      greater inhibition of cAMP. Parallel studies using somatostatin, cyclopentyl
      adenosine, or ACh to activate, respectively, Gi1-coupled somatostatin (sstr3)
      receptors, and Gi3-coupled adenosine A1 or muscarinic m2 receptors elicited cSrc
      activation, Galphai1 or Galphai3 phosphorylation, Galphai1-RGS12 or Galphai3
      RGS12 association, and inhibition of cAMP. Inhibition of cAMP and muscle
      relaxation was greatly increased by AS-605240 and PP2. The results demonstrate
      that Gbetagamma-dependent tyrosine phosphorylation of Galphai1/2/3 by cSrc
      facilitated recruitment of RGS12, a Galphai-specific RGS protein with a unique
      phosphotyrosine-binding domain, resulting in rapid deactivation of Galphai and
      facilitation of smooth muscle relaxation.

PMID- 24578344
TI  - VPAC1 receptors regulate intestinal secretion and muscle contractility by
      activating cholinergic neurons in guinea pig jejunum.
AB  - In the gastrointestinal tract, vasoactive intestinal peptide (VIP) is found
      exclusively within neurons. VIP regulates intestinal motility via neurally
      mediated and direct actions on smooth muscle and secretion by a direct mucosal
      action, and via actions on submucosal neurons. VIP acts via VPAC1 and VPAC2
      receptors; however, the subtype involved in its neural actions is unclear. The
      neural roles of VIP and VPAC1 receptors (VPAC1R) were investigated in intestinal
      motility and secretion in guinea pig jejunum. Expression of VIP receptors across
      the jejunal layers was examined using RT-PCR. Submucosal and myenteric neurons
      expressing VIP receptor subtype VPAC1 and/or various neurochemical markers were
      identified immunohistochemically. Isotonic muscle contraction was measured in
      longitudinal muscle-myenteric plexus preparations. Electrogenic secretion across
      mucosa-submucosa preparations was measured in Ussing chambers by monitoring short
      circuit current. Calretinin(+) excitatory longitudinal muscle motor neurons
      expressed VPAC1R. Most cholinergic submucosal neurons, notably NPY(+)
      secretomotor neurons, expressed VPAC1R. VIP (100 nM) induced longitudinal muscle
      contraction that was inhibited by TTX (1 MUM), PG97-269 (VPAC1 antagonist; 1
      MUM), and hyoscine (10 MUM), but not by hexamethonium (200 MUM). VIP (50 nM)
      evoked secretion was depressed by hyoscine or PG97-269 and involved a small TTX
      sensitive component. PG97-269 and TTX combined did not further depress the VIP
      response observed in the presence of PG97-269 alone. We conclude that VIP
      stimulates ACh-mediated longitudinal muscle contraction via VPAC1R on cholinergic
      motor neurons. VIP induces Cl(-) secretion directly via epithelial VPAC1R and
      indirectly via VPAC1R on cholinergic secretomotor neurons. No evidence was
      obtained for involvement of other neural VIP receptors.

PMID- 24578346
TI  - Prescriptions for category D and X drugs during pregnancy in Taiwan: a population
      based study.
AB  - PURPOSE: This study aimed to investigate the most prescribed medications and
      principle diagnoses for category D and X drugs during pregnancy using a
      population-based dataset in Taiwan. METHODS: The data for the present study were
      sourced from the Taiwan Longitudinal Health Insurance Database 2000. We selected
      14 125 women who had live singleton births between 1 January 2009 and 31 December
      2011. In total, 217 226 prescriptions prescribed to these pregnant women were
      identified. RESULTS: Of the total 217 226 prescriptions, 1.1% were category D or
      X drugs; in the first, second, and third trimesters of pregnancy, 1.8%, 0.7%, and
      0.5% of prescriptions were category D or X drugs, respectively. Progestins
      (15.3%) and propylthiouracil (10.7%) were the two most frequently prescribed
      category D or X drugs during pregnancy. In particular, progestins (20.4%) and
      estrogens (15.6%) were the most frequently prescribed category D or X drug in the
      first trimester of pregnancy. Propylthiouracil was the most prescribed category D
      or X drug in the second (20.3%) and third trimesters (23.1%) of pregnancy,
      respectively. The most common principal diagnosis during pregnancy was "disorders
      of menstruation and other abnormal bleeding from the female genital tract" (22%
      of all principal diagnoses for prescribing category D and X drugs). CONCLUSIONS:
      Our study found that the physicians obviously reduced the use of category D and X
      drugs for women after becoming aware that they were pregnant.

PMID- 24578348
TI  - An old dilemma: is the pap smear a valid test to detect Neisseria gonorrhoeae in
      asymptomatic women?

PMID- 24578347
TI  - GCNF-dependent activation of cyclin D1 expression via repression of Mir302a
      during ESC differentiation.
AB  - Cyclin D1 plays an important role in the regulation of cellular proliferation and
      its expression is activated during gastrulation in the mouse; however, it remains
      unknown how cyclin D1 expression is regulated during early embryonic development.
      Here, we define the role of germ cell nuclear factor (GCNF) in the activation of
      cyclin D1 expression during embryonic stem cell (ESC) differentiation as a model
      of early development. During our study of GCNF knockout (GCNF(-) (/) (-) ) ESC,
      we discovered that loss of GCNF leads to the repression of cyclin D1 activation
      during ESC differentiation. This was determined to be an indirect effect of
      deregulation Mir302a, which is a cyclin D1 suppressor via binding to the 3'UTR of
      cyclin D1 mRNA. Moreover, we showed that Mir302 is a target gene of GCNF that
      inhibits Mir302 expression by binding to a DR0 element within its promoter.
      Inhibition of Mir302a using Mir302 inhibitor during differentiation of GCNF(-)
      (/) (-) ESCs restored cyclin D1 expression. Similarly over-expression of GCNF
      during differentiation of GCNF(-) (/) (-) ESCs rescued the inhibition of Mir302a
      expression and the activation of cyclin D1. These results reveal that GCNF plays
      a key role in regulating activation of cyclin D1 expression via inhibition of
      Mir302a.

PMID- 24578345
TI  - Quantitative radiologic imaging techniques for articular cartilage composition:
      toward early diagnosis and development of disease-modifying therapeutics for
      osteoarthritis.

PMID- 24578349
TI  - Maintenance of heterochromatin boundary and nucleosome composition at promoters
      by the Asf1 histone chaperone and SWR1-C chromatin remodeler in Saccharomyces
      cerevisiae.
AB  - Chromatin remodeling complexes cooperate to regulate gene promoters and to define
      chromatin neighborhoods. Here, we identified genetic and functional connections
      between two silencing-related chromatin factors in the maintenance of native
      heterochromatic structures and nucleosome composition at promoters. Building on a
      previously reported link between the histone chaperone Asf1 and the Yaf9 subunit
      of the SWR1-C chromatin remodeler, we found that ASF1 broadly interacted with
      genes encoding for SWR1-C subunits. Asf1 and Yaf9 were required for maintaining
      expression of heterochromatin-proximal genes and they worked cooperatively to
      prevent repression of telomere-proximal genes by limiting the spread of SIR
      complexes into nearby regions. Genome-wide Sir2 profiling, however, revealed that
      the cooperative heterochromatin regulation of Asf1 and SWR1-C occurred only on a
      subset of yeast telomeres. Extensive analyses demonstrated that formation of
      aberrant heterochromatin structures in the absence of ASF1 and YAF9 was not
      causal for the pronounced growth and transcriptional defects in cells lacking
      both these factors. Instead, genetic and molecular analysis revealed that H3K56
      acetylation was required for efficient deposition of H2A.Z at subtelomeric and
      euchromatic gene promoters, pointing to a role for Asf1-dependent H3K56
      acetylation in SWR1-C biology. 

PMID- 24578350
TI  - High-resolution sex-specific linkage maps of the mouse reveal polarized
      distribution of crossovers in male germline.
AB  - Since the publication of the first comprehensive linkage map for the laboratory
      mouse, the architecture of recombination as a basic biological process has become
      amenable to investigation in mammalian model organisms. Here we take advantage of
      high-density genotyping and the unique pedigree structure of the incipient
      Collaborative Cross to investigate the roles of sex and genetic background in
      mammalian recombination. Our results confirm the observation that map length is
      longer when measured through female meiosis than through male meiosis, but we
      find that this difference is modified by genotype at loci on both the X
      chromosome and the autosomes. In addition, we report a striking concentration of
      crossovers in the distal ends of autosomes in male meiosis that is absent in
      female meiosis. The presence of this pattern in both single- and double
      recombinant chromosomes, combined with the absence of a corresponding asymmetry
      in the distribution of double-strand breaks, indicates a regulated sequence of
      events specific to male meiosis that is anchored by chromosome ends. This pattern
      is consistent with the timing of chromosome pairing and evolutionary constraints
      on male recombination. Finally, we identify large regions of reduced crossover
      frequency that together encompass 5% of the genome. Many of these "cold regions"
      are enriched for segmental duplications, suggesting an inverse local correlation
      between recombination rate and mutation rate for large copy number variants. 

PMID- 24578351
TI  - Birth, death, and diversification of mobile promoters in prokaryotes.
AB  - A previous study of prokaryotic genomes identified large reservoirs of putative
      mobile promoters (PMPs), that is, homologous promoter sequences associated with
      nonhomologous coding sequences. Here we extend this data set to identify the full
      complement of mobile promoters in sequenced prokaryotic genomes. The expanded
      search identifies nearly 40,000 PMP sequences, 90% of which occur in noncoding
      regions of the genome. To gain further insight from this data set, we develop a
      birth-death-diversification model for mobile genetic elements subject to sequence
      diversification; applying the model to PMPs we are able to quantify the relative
      importance of duplication, loss, horizontal gene transfer (HGT), and
      diversification to the maintenance of the PMP reservoir. The model predicts low
      rates of HGT relative to the duplication and loss of PMP copies, rapid dynamics
      of PMP families, and a pool of PMPs that exist as a single copy in a genome at
      any given time, despite their mobility. We report evidence of these "singletons"
      at high frequencies in prokaryotic genomes. We also demonstrate that including
      selection, either for or against PMPs, was not necessary to describe the observed
      data. 

PMID- 24578353
TI  - Association of thigh muscle strength with knee symptoms and radiographic disease
      stage of osteoarthritis: data from the Osteoarthritis Initiative.
AB  - OBJECTIVE: To determine whether thigh muscle strength differs between symptomatic
      and asymptomatic knees, and/or different radiographic strata of knee
      osteoarthritis (KOA). METHODS: Isometric extensor and flexor strength were
      analyzed in 3,809 Osteoarthritis Initiative participants (2,201 women and 1,608
      men) with central radiographic Kellgren/Lawrence (K/L) grade readings. Isometric
      strength measurements were stratified by radiographic disease status (K/L grades
      0, 1, 2, and 3/4) and Western Ontario and McMaster Universities Osteoarthritis
      Index (WOMAC) pain scores. Age-adjusted, separate-slopes analysis of covariance
      models was used to compare strength between "symptomatic" (WOMAC score range 5
      20) and "asymptomatic" (WOMAC score = 0) legs within and across K/L grade strata.
      Exploratory analyses focused on strength normalized to body weight and symptom
      frequency. RESULTS: Isometric strength was significantly lower in symptomatic
      than in asymptomatic legs: -11 to -13% for extensor strength and -7 to -16% for
      flexor strength (P < 0.0001 for both) in men, and -9 to -17% (P = 0.029) for
      extensor strength, and -10 to -21% (P = 0.049) for flexor strength in women.
      Similar observations were made for pain frequency strata. Extensor and flexor
      strength were not significantly different across K/L grade strata in asymptomatic
      legs in either sex (P >= 0.12). However, strength normalized to body weight was
      lower at higher K/L grades in both sexes (P <= 0.02) because the body mass index
      was greater in participants with more advanced radiographic disease. CONCLUSION:
      Knee symptoms (i.e., pain) appear to be the relevant determinant of isometric
      knee extensor and flexor strength in KOA, whereas no direct association between
      strength and radiographic severity was observed. These findings suggest that the
      reduction in thigh muscle strength in KOA is related to pain but not to the
      structural (radiographic) disease status.

PMID- 24578352
TI  - Signatures of sex-antagonistic selection on recombining sex chromosomes.
AB  - Sex-antagonistic (SA) selection has major evolutionary consequences: it can drive
      genomic change, constrain adaptation, and maintain genetic variation for fitness.
      The recombining (or pseudoautosomal) regions of sex chromosomes are a promising
      setting in which to study SA selection because they tend to accumulate SA
      polymorphisms and because recombination allows us to deploy the tools of
      molecular evolution to locate targets of SA selection and quantify evolutionary
      forces. Here we use coalescent models to characterize the patterns of
      polymorphism expected within and divergence between recombining X and Y (or Z and
      W) sex chromosomes. SA selection generates peaks of divergence between X and Y
      that can extend substantial distances away from the targets of selection. Linkage
      disequilibrium between neutral sites is also inflated. We show how the pattern of
      divergence is altered when the SA polymorphism or the sex-determining region was
      recently established. We use data from the flowering plant Silene latifolia to
      illustrate how the strength of SA selection might be quantified using molecular
      data from recombining sex chromosomes. 

PMID- 24578355
TI  - StaphyloBase: a specialized genomic resource for the staphylococcal research
      community.
AB  - With the advent of high-throughput sequencing technologies, many staphylococcal
      genomes have been sequenced. Comparative analysis of these strains will provide
      better understanding of their biology, phylogeny, virulence and taxonomy, which
      may contribute to better management of diseases caused by staphylococcal
      pathogens. We developed StaphyloBase with the goal of having a one-stop genomic
      resource platform for the scientific community to access, retrieve, download,
      browse, search, visualize and analyse the staphylococcal genomic data and
      annotations. We anticipate this resource platform will facilitate the analysis of
      staphylococcal genomic data, particularly in comparative analyses. StaphyloBase
      currently has a collection of 754 032 protein-coding sequences (CDSs), 19 258
      rRNAs and 15 965 tRNAs from 292 genomes of different staphylococcal species.
      Information about these features is also included, such as putative functions,
      subcellular localizations and gene/protein sequences. Our web implementation
      supports diverse query types and the exploration of CDS- and RNA-type information
      in detail using an AJAX-based real-time search system. JBrowse has also been
      incorporated to allow rapid and seamless browsing of staphylococcal genomes. The
      Pairwise Genome Comparison tool is designed for comparative genomic analysis, for
      example, to reveal the relationships between two user-defined staphylococcal
      genomes. A newly designed Pathogenomics Profiling Tool (PathoProT) is also
      included in this platform to facilitate comparative pathogenomics analysis of
      staphylococcal strains. In conclusion, StaphyloBase offers access to a range of
      staphylococcal genomic resources as well as analysis tools for comparative
      analyses. Database URL: http://staphylococcus.um.edu.my/.

PMID- 24578354
TI  - Endothelial FoxM1 mediates bone marrow progenitor cell-induced vascular repair
      and resolution of inflammation following inflammatory lung injury.
AB  - Adult stem cell treatment is a potential novel therapeutic approach for acute
      respiratory distress syndrome. Given the extremely low rate of cell engraftment,
      it is believed that these cells exert their beneficial effects via paracrine
      mechanisms. However, the endogenous mediator(s) in the pulmonary vasculature
      remains unclear. Using the mouse model with endothelial cell (EC)-restricted
      disruption of FoxM1 (FoxM1 CKO), here we show that endothelial expression of the
      reparative transcriptional factor FoxM1 is required for the protective effects of
      bone marrow progenitor cells (BMPC) against LPS-induced inflammatory lung injury
      and mortality. BMPC treatment resulted in rapid induction of FoxM1 expression in
      wild type (WT) but not FoxM1 CKO lungs. BMPC-induced inhibition of lung vascular
      injury, resolution of lung inflammation, and survival, as seen in WT mice, were
      abrogated in FoxM1 CKO mice following LPS challenge. Mechanistically, BMPC
      treatment failed to induce lung EC proliferation in FoxM1 CKO mice, which was
      associated with impaired expression of FoxM1 target genes essential for cell
      cycle progression. We also observed that BMPC treatment enhanced endothelial
      barrier function in WT but not in FoxM1-deficient EC monolayers. Restoration of
      beta-catenin expression in FoxM1-deficient ECs normalized endothelial barrier
      enhancement in response to BMPC treatment. These data demonstrate the requisite
      role of endothelial FoxM1 in the mechanism of BMPC-induced vascular repair to
      restore vascular integrity and accelerate resolution of inflammation, thereby
      promoting survival following inflammatory lung injury.

PMID- 24578356
TI  - The Zebrafish GenomeWiki: a crowdsourcing approach to connect the long tail for
      zebrafish gene annotation.
AB  - A large repertoire of gene-centric data has been generated in the field of
      zebrafish biology. Although the bulk of these data are available in the public
      domain, most of them are not readily accessible or available in nonstandard
      formats. One major challenge is to unify and integrate these widely scattered
      data sources. We tested the hypothesis that active community participation could
      be a viable option to address this challenge. We present here our approach to
      create standards for assimilation and sharing of information and a system of open
      standards for database intercommunication. We have attempted to address this
      challenge by creating a community-centric solution for zebrafish gene annotation.
      The Zebrafish GenomeWiki is a 'wiki'-based resource, which aims to provide an
      altruistic shared environment for collective annotation of the zebrafish genes.
      The Zebrafish GenomeWiki has features that enable users to comment, annotate,
      edit and rate this gene-centric information. The credits for contributions can be
      tracked through a transparent microattribution system. In contrast to other
      wikis, the Zebrafish GenomeWiki is a 'structured wiki' or rather a 'semantic
      wiki'. The Zebrafish GenomeWiki implements a semantically linked data structure,
      which in the future would be amenable to semantic search. Database URL:
      http://genome.igib.res.in/twiki. 

PMID- 24578357
TI  - Learning regular expressions for clinical text classification.
AB  - OBJECTIVES: Natural language processing (NLP) applications typically use regular
      expressions that have been developed manually by human experts. Our goal is to
      automate both the creation and utilization of regular expressions in text
      classification. METHODS: We designed a novel regular expression discovery (RED)
      algorithm and implemented two text classifiers based on RED. The RED+ALIGN
      classifier combines RED with an alignment algorithm, and RED+SVM combines RED
      with a support vector machine (SVM) classifier. Two clinical datasets were used
      for testing and evaluation: the SMOKE dataset, containing 1091 text snippets
      describing smoking status; and the PAIN dataset, containing 702 snippets
      describing pain status. We performed 10-fold cross-validation to calculate
      accuracy, precision, recall, and F-measure metrics. In the evaluation, an SVM
      classifier was trained as the control. RESULTS: The two RED classifiers achieved
      80.9-83.0% in overall accuracy on the two datasets, which is 1.3-3% higher than
      SVM's accuracy (p<0.001). Similarly, small but consistent improvements have been
      observed in precision, recall, and F-measure when RED classifiers are compared
      with SVM alone. More significantly, RED+ALIGN correctly classified many instances
      that were misclassified by the SVM classifier (8.1-10.3% of the total instances
      and 43.8-53.0% of SVM's misclassifications). CONCLUSIONS: Machine-generated
      regular expressions can be effectively used in clinical text classification. The
      regular expression-based classifier can be combined with other classifiers, like
      SVM, to improve classification performance.

PMID- 24578360
TI  - Future of public workforce training: thought leaders' perspectives.
AB  - The guest editors identified eleven prominent public health thought leaders from
      practice, academia, professional associations, and philanthropic organizations to
      be interviewed for their opinions about the future of public health, the skills
      needed by the public health workforce, and training opportunities and roles.
      While they spoke from many different perspectives, several overarching themes
      emerged. The public health workforce needs updated skills. Public health academia
      should be more engaged in educating and training for public health practice,
      which would also benefit academia. There is a sense that "now is the time" for
      public health to be an essential player in the health care system. They see
      promise in emerging activities such as accreditation, practice-based research,
      and an explicit national agenda for workforce training. Overall, they are
      cautiously optimistic about the potential for greater real and perceived value of
      public health, momentum for more comprehensive, and coordinated public health
      training. 

PMID- 24578359
TI  - Direct, indirect, total, and overall effectiveness of the rotavirus vaccines for
      the prevention of gastroenteritis hospitalizations in privately insured US
      children, 2007-2010.
AB  - We demonstrate how direct, indirect, total, and overall effectiveness estimates
      and absolute benefits of rotavirus vaccines vary through the years following
      vaccine introduction. Privately insured US children in a large claims database
      were followed from age 8 months until they 1) experienced a hospitalization for
      rotavirus or acute gastroenteritis; 2) lost continuous health plan enrollment; 3)
      turned 20 months of age; or 4) reached the end of the study period. Vaccine
      effectiveness estimates in preventing rotavirus and acute gastroenteritis
      hospitalizations were estimated using Cox proportional hazards regression,
      stratified by calendar year and adjusted for birth month. Incidence rate
      differences were estimated to determine the absolute number of gastroenteritis
      hospitalizations prevented in the cohort. Among 905,718 children, 51%, 66%, 80%,
      and 86% received 1 or more doses of rotavirus vaccine in each year from 2007 to
      2010. The direct vaccine effectiveness of 1 or more doses of rotavirus vaccine in
      preventing rotavirus gastroenteritis hospitalizations ranged from 87% to 92% each
      year. Accounting for indirect protection increased estimates of vaccine
      effectiveness by an additional 3%-8% among those vaccinated. Failing to account
      for population-level vaccine benefits in 2010, when circulation of rotavirus was
      low, could underestimate the sustained impact of the vaccine program. 

PMID- 24578361
TI  - A collaborative approach in workforce assessment: South Carolina's strategies for
      high response rates.
AB  - The South Carolina Public Health Training Center and South Carolina Department of
      Health and Environmental Control conducted a state public health workforce
      assessment using a collaborative methodology. A joint workforce assessment team
      used the 2010 Core Competencies for Public Health Professionals--developed by the
      Council on Linkages Between Academia and Public Health Practice--as the basis for
      the assessment and resulting continuing education programs. A 91% response rate
      (n = 1,375) was achieved among full-time regional employees, while an 81%
      response rate (n = 1,598) was achieved among all regional employee types. This
      unusually high response rate in a voluntary assessment was accomplished by
      involving key stakeholders in the planning, development, and implementation
      process and by communicating directly with leaders in South Carolina's eight
      health regions. In addition to boosting the response rate, the collaborative
      approach strengthened the partnership between the academic and practice partners.
      In this article, we discuss the workforce assessment methodology, strategies,
      results, and lessons learned.

PMID- 24578358
TI  - The relationship between alcohol consumption and vascular complications and
      mortality in individuals with type 2 diabetes.
AB  - OBJECTIVE: Moderate alcohol consumption has been associated with a reduced risk
      of mortality and coronary artery disease. The relationship between cardiovascular
      health and alcohol use in type 2 diabetes is less clear. The current study
      assesses the effects of alcohol use among participants in the Action in Diabetes
      and Vascular Disease: Preterax and Diamicron Modified-Release Controlled
      Evaluation (ADVANCE) trial. RESEARCH DESIGN AND METHODS: The effects of alcohol
      use were explored using Cox regression models, adjusted for potential
      confounders. The study end points were cardiovascular events (cardiovascular
      death, myocardial infarction, and stroke), microvascular complications (new or
      worsening nephropathy or retinopathy), and all-cause mortality. RESULTS: During a
      median of 5 years of follow-up, 1,031 (9%) patients died, 1,147 (10%) experienced
      a cardiovascular event, and 1,136 (10%) experienced a microvascular complication.
      Compared with patients who reported no alcohol consumption, those who reported
      moderate consumption had fewer cardiovascular events (adjusted hazard ratio [aHR]
      0.83; 95% CI 0.72-0.95; P = 0.008), less microvascular complications (aHR 0.85;
      95% CI 0.73-0.99; P = 0.03), and lower all-cause mortality (aHR 0.87; 96% CI 0.75
      1.00; P = 0.05). The benefits were particularly evident in participants who drank
      predominantly wine (cardiovascular events aHR 0.78, 95% CI 0.63-0.95, P = 0.01;
      all-cause mortality aHR 0.77, 95% CI 0.62-0.95, P = 0.02). Compared with patients
      who reported no alcohol consumption, those who reported heavy consumption had
      dose-dependent higher risks of cardiovascular events and all-cause mortality.
      CONCLUSIONS: In patients with type 2 diabetes, moderate alcohol use, particularly
      wine consumption, is associated with reduced risks of cardiovascular events and
      all-cause mortality.

PMID- 24578362
TI  - A needs assessment of health department employees in Puerto Rico and Florida.
AB  - Public health training centers were established to enhance competencies in skills
      required to meet 21st-century public health challenges. In 2011, the Puerto Rico
      Florida Public Health Training Center conducted surveys to assess the training
      needs of two populations of public health workers serving Hispanic communities:
      Florida Department of Health employees and workers at the regional and central
      offices of the Puerto Rico Department of Health. The two surveys were similar,
      but not identical in content and administration. A 52.6% response rate was
      achieved in the Commonwealth of Puerto Rico, where limited computer access
      necessitated use of a pen-and-paper survey. A 20.7% response rate was achieved in
      Florida, where an online survey was used and incomplete responses were
      problematic. Puerto Rico respondents (n = 1,414) were similar in age (Mdn age =
      48 years) to Hispanic Florida respondents (n = 546, Mdn age =45 years). They also
      reported higher levels of academic achievement and more years of experience in
      public health. Nevertheless, self-assessed public health competency scores were
      in the low- to mid-range for Hispanic respondents in both locales. Although self
      assessed training priorities differed, Hispanic employees in both jurisdictions
      preferred hands-on and face-to-face training to distance learning. Findings
      indicate a need for training based on adult learning theory, targeted to entry
      level employees, and addressing the top five self-assessed training needs,
      especially health promotion and disease prevention and public health law and
      policy, which emerged as priority training areas in both survey populations. 

PMID- 24578363
TI  - Charting a course to competency: an approach to mapping public health core
      competencies to existing trainings.
AB  - Consistent with other professional fields, the goals of public health training
      have moved from a focus on knowledge transfer to the development of skills or
      competencies. At least six national competency sets have been developed in the
      past decade pertaining to public health professionals. State and local public
      health agencies are increasingly using competency sets as frameworks for staff
      development and assessment. Mapping competencies to training has potential for
      enhancing the value of public health training during resource-constrained times
      by directly linking training content to the desired skills. For existing public
      health trainings, the challenge is how to identify competencies addressed in
      those courses in a manner that is not burdensome and that produces valid results.
      This article describes a process for mapping competencies to the learning
      objectives, assignments, and assessments of existing trainings. The process
      presented could be used by any training center or organization that seeks to
      connect public health workforce competencies to previously developed instruction.
      Public health practice can be strengthened more effectively if trainings can be
      selected for the desired practice skills or competencies. 

PMID- 24578365
TI  - On your time: online training for the public health workforce.
AB  - The need for competency-based training for the public health workforce is well
      documented. However, human and financial resource limitations within public
      health agencies often make it difficult for public health practitioners to attend
      classroom-based training programs. The Internet is an increasingly popular way of
      extending training beyond the workforce. Although research describes attributes
      of effective online learning modules, much of the available training delivered
      via the Internet does not incorporate such attributes. The authors describe the
      On Your Time training series, an effective distance education program and
      training model for public health practitioners, which includes a standardized
      process for development, review, evaluation, and continuous quality improvement.
      On Your Time is a series of awareness-level (i.e., addressing what practitioners
      should know), competency-based training modules that address topics related to
      regulatory responsibilities of public health practitioners (e.g., assuring
      compliance with codes and regulations governing housing, retail food safety,
      private water supplies, hazardous and solid waste, on-site wastewater systems,
      etc.), public health surveillance, case investigation, disease prevention, health
      promotion, and emergency preparedness. The replicable model incorporates what is
      known about best practices for online training and maximizes available resources
      in the interests of sustainability. 

PMID- 24578364
TI  - Using innovative instructional technology to meet training needs in public
      health: a design process.
AB  - Technology and distance learning can potentially enhance the efficient and
      effective delivery of continuing education to the public health workforce. Public
      Health Training Centers collaborate with instructional technology designers to
      develop innovative, competency-based online learning experiences that meet
      pressing training needs and promote best practices. We describe one Public Health
      Training Center's online learning module design process, which consists of five
      steps: (1) identify training needs and priority competencies; (2) define learning
      objectives and identify educational challenges; (3) pose hypotheses and explore
      innovative, technology-based solutions; (4) develop and deploy the educational
      experience; and (5) evaluate feedback and outcomes to inform continued cycles of
      revision and improvement. Examples illustrate the model's application. These
      steps are discussed within the context of design practices in the fields of
      education, engineering, and public health. They incorporate key strategies from
      across these fields, including principles of programmatic design familiar to
      public health professionals, such as backward design. The instructional
      technology design process we describe provides a structure for the creativity,
      collaboration, and systematic strategies needed to develop online learning
      products that address critical training needs for the public health workforce. 

PMID- 24578366
TI  - An instructional design model for culturally competent community health worker
      training.
AB  - The Texas Public Health Training Center (TPHTC) provides quality training and
      education for the full spectrum of public health workers. As part of this
      mission, the TPHTC creates continuing education modules for nontraditional public
      health workers, such as community health workers (CHWs), through a culturally
      competent curriculum development process. CHWs, like many public health workers,
      must be certified by the state of Texas to practice within its borders, and
      continuing education is required to maintain certification. By involving CHWs and
      community members in its curriculum development process, the TPHTC is able to
      produce training modules that are more suitable for this unique and important
      segment of the public health workforce. The iterative curriculum development
      process is described here, along with a state-approved curriculum resulting from
      this method. As the value of the nontraditional public health workforce gains
      more recognition, sound curriculum design will be increasingly important to
      support and strengthen these nontraditional professions. 

PMID- 24578367
TI  - Public Health Training Centers: strategies for preparing the public health
      workforce.

PMID- 24578368
TI  - The public health leadership certificate: a public health and primary care
      interprofessional training opportunity.
AB  - This article describes a public health leadership certificate curriculum
      developed by the Commonwealth Public Health Training Center for employees in
      public health and medical trainees in primary care to share didactic and
      experiential learning. As part of the program, trainees are involved in improving
      the health of their communities and thus gain a blended perspective on the
      effectiveness of interprofessional teams in improving population health. The
      certificate curriculum includes eight one-credit-hour didactic courses offered
      through an MPH program and a two-credit-hour, community-based participatory
      research project conducted by teams of trainees under the mentorship of health
      district directors. Fiscal sustainability is achieved by sharing didactic courses
      with MPH degree students, thereby enabling trainees to take advantage of a
      reduced, continuing education tuition rate. Public health employee and primary
      care trainees jointly learn knowledge and skills required for community health
      improvement in interprofessional teams and gain an integrated perspective through
      opportunities to question assumptions and broaden disciplinary approaches. At the
      same time, the required community projects have benefited public health in
      Virginia. 

PMID- 24578369
TI  - A Regional Public Health Field Placement Program: making an IMPACT.
AB  - Beginning in 2010, the U.S. Department of Health and Human Services, Health
      Resources and Services Administration, made provisions in its Public Health
      Training Center cooperative agreements for field placements. This article
      describes best practices and lessons learned establishing and managing the South
      Central Public Health Partnership's Interns and Mentors Program for ACTion
      (IMPACT) Field Placement Program, which was initially funded through the Centers
      for Disease Control and Prevention's Centers for Public Health Preparedness
      Cooperative agreement in 2002. The IMPACT program is based on a six-step process
      that has been developed and refined over its 10-year history: (a) identifying
      field placement opportunities, (b) marketing field experience opportunities to
      students, (c) selecting students seeking field experience opportunities, (d)
      placing students with practice partners, students with practice partners, (e)
      evaluating student progress toward field experience objectives, and (f)
      evaluating the program. This article describes the program's structure and
      processes, delineates the roles of its academic and practice partners, discusses
      evidence of its effectiveness, and describes lessons learned from its decade-long
      history. Hopefully, this information will facilitate the establishment,
      management and evaluation of internship and field placement programs in other
      Public Health Training Centers and academic public health programs. 

PMID- 24578370
TI  - Public health training center evaluation: a framework for using logic models to
      improve practice and educate the public health workforce.
AB  - The nation's 37 public health training centers (PHTCs) provide competency-based
      trainings and practice-based opportunities to advance the current and future
      public health workforces. The Emory PHTC, based in Atlanta, Georgia, has
      developed a comprehensive evaluation plan to address the many evaluation-related
      questions that must be answered to inform decisions that improve practice. This
      plan, based on the center's logic model, includes formative assessment, outcome
      evaluation, process evaluation, and programmatic evaluation. Rigorous evaluation
      has been used to (a) assess what is working, what is not working, and why; (b)
      guide decision making about program improvement; and (c) ensure efficient use of
      resources, such as time and money. This article describes how the Emory PHTC uses
      its logic model to guide development of a comprehensive evaluation plan and to
      create specific data collection tools. It also explains the process used to
      analyze data and make decisions to maximize effectiveness and ensure the best use
      of resources. Simply conducting trainings and providing opportunities for real
      world application are not enough; it is critical to assess whether or not these
      educational opportunities are, in fact, educating. 

PMID- 24578371
TI  - The meaning of "independence" for older people in different residential settings.
AB  - OBJECTIVES: Drawing on older people's understandings of "independence" and
      Collopy's work on autonomy, the article elaborates an interpretive framework of
      the concept in relation to 3 residential settings-the private dwelling-home, the
      extra-care, and the residential-care settings. METHOD: Data include 91
      qualitative interviews with frail, older people living in each setting, collected
      as part of a larger Welsh study. Thematic analysis techniques were employed to
      identify patterns in meanings of independence across settings and then
      interpreted using Collopy's conceptualizations of autonomy, as well as notions of
      space and interdependencies. RESULTS: Independence has multiple meanings for
      older people, but certain meanings are common to all settings: Accepting help at
      hand; doing things alone; having family, friends, and money as resources; and
      preserving physical and mental capacities. Concepts of delegated, executional,
      authentic, decisional, and consumer autonomy, as well as social interdependencies
      and spatial and social independence, do provide appropriate higher order
      interpretive constructs of these meanings across settings. DISCUSSION: A broader
      interpretive framework of "independence" should encompass concepts of relative
      independence, autonomy(ies), as well as spatial and social independence, and can
      provide more nuanced interpretations of structured dependency and
      institutionalization theories when applied to different residential settings.

PMID- 24578373
TI  - Temporal relations between methamphetamine use and HIV seroconversion in gay,
      bisexual, and other men who have sex with men.
AB  - Data from a cross-sectional study of gay, bisexual, and other men who have sex
      with men who were active methamphetamine users were analyzed to assess temporal
      relations between HIV seroconversion and initiation of methamphetamine use. Of
      the 100 men, 58 reported being HIV-positive. Most HIV-positive participants (65%)
      initiated methamphetamine use after seroconverting. Among those who initiated use
      before seroconversion, 8 years elapsed between onset of use and time of
      infection. Findings suggest the need to develop nuanced and targeted
      interventions aimed at disentangling the "meth-sex" link in this population.
      Findings also suggest use of the drug as a coping mechanism for those living with
      HIV. 

PMID- 24578372
TI  - Construction of pseudomolecule sequences of the aus rice cultivar Kasalath for
      comparative genomics of Asian cultivated rice.
AB  - Having a deep genetic structure evolved during its domestication and adaptation,
      the Asian cultivated rice (Oryza sativa) displays considerable physiological and
      morphological variations. Here, we describe deep whole-genome sequencing of the
      aus rice cultivar Kasalath by using the advanced next-generation sequencing (NGS)
      technologies to gain a better understanding of the sequence and structural
      changes among highly differentiated cultivars. The de novo assembled Kasalath
      sequences represented 91.1% (330.55 Mb) of the genome and contained 35 139
      expressed loci annotated by RNA-Seq analysis. We detected 2 787 250 single
      nucleotide polymorphisms (SNPs) and 7393 large insertion/deletion (indel) sites
      (>100 bp) between Kasalath and Nipponbare, and 2 216 251 SNPs and 3780 large
      indels between Kasalath and 93-11. Extensive comparison of the gene contents
      among these cultivars revealed similar rates of gene gain and loss. We detected
      at least 7.39 Mb of inserted sequences and 40.75 Mb of unmapped sequences in the
      Kasalath genome in comparison with the Nipponbare reference genome. Mapping of
      the publicly available NGS short reads from 50 rice accessions proved the
      necessity and the value of using the Kasalath whole-genome sequence as an
      additional reference to capture the sequence polymorphisms that cannot be
      discovered by using the Nipponbare sequence alone. 

PMID- 24578375
TI  - Journals should lead the way in improving medical press releases.

PMID- 24578374
TI  - Genome sequence of Saccharomyces carlsbergensis, the world's first pure culture
      lager yeast.
AB  - Lager yeast beer production was revolutionized by the introduction of pure
      culture strains. The first established lager yeast strain is known as the bottom
      fermenting Saccharomyces carlsbergensis, which was originally termed Unterhefe
      No. 1 by Emil Chr. Hansen and has been used in production in since 1883. S.
      carlsbergensis belongs to group I/Saaz-type lager yeast strains and is better
      adapted to cold growth conditions than group II/Frohberg-type lager yeasts, e.g.,
      the Weihenstephan strain WS34/70. Here, we sequenced S. carlsbergensis using next
      generation sequencing technologies. Lager yeasts are descendants from hybrids
      formed between a S. cerevisiae parent and a parent similar to S. eubayanus.
      Accordingly, the S. carlsbergensis 19.5-Mb genome is substantially larger than
      the 12-Mb S. cerevisiae genome. Based on the sequence scaffolds, synteny to the
      S. cerevisae genome, and by using directed polymerase chain reaction for gap
      closure, we generated a chromosomal map of S. carlsbergensis consisting of 29
      unique chromosomes. We present evidence for genome and chromosome evolution
      within S. carlsbergensis via chromosome loss and loss of heterozygosity
      specifically of parts derived from the S. cerevisiae parent. Based on our
      sequence data and via fluorescence-activated cell-sorting analysis, we determined
      the ploidy of S. carlsbergensis. This inferred that this strain is basically
      triploid with a diploid S. eubayanus and haploid S. cerevisiae genome content. In
      contrast the Weihenstephan strain, which we resequenced, is essentially
      tetraploid composed of two diploid S. cerevisiae and S. eubayanus genomes. Based
      on conserved translocations between the parental genomes in S. carlsbergensis and
      the Weihenstephan strain we propose a joint evolutionary ancestry for lager yeast
      strains. 

PMID- 24578376
TI  - Evidences for the involvement of cell surface glycans in stem cell pluripotency
      and differentiation.
AB  - Induced pluripotent stem (iPS) cells are somatic cells that have been
      reprogrammed to a pluripotent state via the introduction of defined transcription
      factors. Although iPS is a potentially valuable resource for regenerative
      medicine and drug development, several issues regarding their pluripotency,
      differentiation propensity and potential for tumorigenesis remain to be
      elucidated. Analysis of cell surface glycans has arisen as an interesting tool
      for the characterization of iPS. An appropriate characterization of glycan
      surface molecules of human embryonic stem (hES) cells and iPS cells might
      generate crucial data to highlight their role in the acquisition and maintenance
      of pluripotency. In this study, we characterized the surface glycans of iPS
      generated from menstrual blood-derived mesenchymal cells (iPS-MBMC). We
      demonstrated that, upon spontaneous differentiation, iPS-MBMC present high
      amounts of terminal beta-galactopyranoside residues, pointing to an important
      role of terminal-linked sialic acids in pluripotency maintenance. The removal of
      sialic acids by neuraminidase induces iPS-MBMC and hES cells differentiation,
      prompting an ectoderm commitment. Exposed beta-galactopyranose residues might be
      recognized by carbohydrate-binding molecules found on the cell surface, which
      could modulate intercellular or intracellular interactions. Together, our results
      point for the first time to the involvement of the presence of terminal sialic
      acid in the maintenance of embryonic stem cell pluripotency and, therefore, the
      modulation of sialic acid biosynthesis emerges as a mechanism that may govern
      stem cell differentiation. 

PMID- 24578377
TI  - Adding practical tools to our toolbox: introduction to the special issue on
      quantitative methodologies.

PMID- 24578378
TI  - Mitogen-activated protein kinase phosphatase-1 promotes neovascularization and
      angiogenic gene expression.
AB  - OBJECTIVE: Angiogenesis is the formation of new blood vessels through endothelial
      cell sprouting. This process requires the mitogen-activated protein kinases,
      signaling molecules that are negatively regulated by the mitogen-activated
      protein kinase phosphatase-1 (MKP-1). The purpose of this study was to evaluate
      the role of MKP-1 in neovascularization in vivo and identify associated
      mechanisms in endothelial cells. APPROACH AND RESULTS: We used murine hindlimb
      ischemia as a model system to evaluate the role of MKP-1 in angiogenic growth,
      remodeling, and arteriogenesis in vivo. Genomic deletion of MKP-1 blunted
      angiogenesis in the distal hindlimb and microvascular arteriogenesis in the
      proximal hindlimb. In vitro, endothelial MKP-1 depletion/deletion abrogated
      vascular endothelial growth factor-induced migration and tube formation, and
      reduced proliferation. These observations establish MKP-1 as a positive mediator
      of angiogenesis and contrast with the canonical function of MKP-1 as a mitogen
      activated protein kinase phosphatase, implying an alternative mechanism for MKP-1
      mediated angiogenesis. Cloning and sequencing of MKP-1-bound chromatin identified
      localization of MKP-1 to exonic DNA of the angiogenic chemokine fractalkine, and
      MKP-1 depletion reduced histone H3 serine 10 dephosphorylation on this DNA locus
      and blocked fractalkine expression. In vivo, MKP-1 deletion abrogated ischemia
      induced fractalkine expression and macrophage and T-lymphocyte infiltration in
      distal hindlimbs, whereas fractalkine delivery to ischemic hindlimbs rescued the
      effect of MKP-1 deletion on neovascular hindlimb recovery. CONCLUSIONS: MKP-1
      promoted angiogenic and arteriogenic neovascular growth, potentially through
      dephosphorylation of histone H3 serine 10 on coding-region DNA to control
      transcription of angiogenic genes, such as fractalkine. These observations reveal
      a novel function for MKP-1 and identify MKP-1 as a potential therapeutic target.

PMID- 24578382
TI  - Notice of retraction.

PMID- 24578383
TI  - Gene deletion of protein tyrosine phosphatase 1B protects against sepsis-induced
      cardiovascular dysfunction and mortality.
AB  - OBJECTIVE: Cardiovascular dysfunction is a major cause of mortality in patients
      with sepsis. Recently, we showed that gene deletion or pharmacological inhibition
      of protein tyrosine phosphatase 1B (PTP1B) improves endothelial dysfunction and
      reduces the severity of experimental heart failure. However, the cardiovascular
      effect of PTP1B invalidation in sepsis is unknown. Thus, we explored the
      beneficial therapeutic effect of PTP1B gene deletion on lipopolysaccharide (LPS)
      induced cardiovascular dysfunction, inflammation, and mortality. APPROACH AND
      RESULTS: PTP1B(-/-) or wild-type mice received LPS (15 mg/kg) or vehicle followed
      by subcutaneous fluid resuscitation (saline, 30 mL/kg). alpha-1-dependent
      constriction and endothelium-dependent dilatation, assessed on isolated perfused
      mesenteric arteries, were impaired 8 hours after LPS and significantly improved
      in PTP1B(-/-) mice. This was associated with reduced vascular expression of
      interleukin1-beta, intercellular adhesion molecule-1, vascular cell adhesion
      molecule-1, cyclooxygenase-2, and inducible nitric oxide synthase mRNA. PTP1B
      gene deletion also limited LPS-induced cardiac dysfunction assessed by
      echocardiography, left ventricular pressure-volume curves, and in isolated
      perfused hearts. PTP1B(-/-) mice also displayed reduced LPS-induced cardiac
      expression of tumor necrosis factor-alpha, interleukin1-beta, intercellular
      adhesion molecule-1, vascular cell adhesion molecule-1, and Gp91phox, as well as
      of several markers of cellular infiltration. PTP1B deficiency also reduced
      cardiac P38 and extracellular signal-regulated protein kinase 1 and 2
      phosphorylation and increased phospholamban phosphorylation. Finally, PTP1B(-/-)
      mice displayed a markedly reduced LPS-induced mortality, an effect also observed
      using a pharmacological PTP1B inhibitor. PTP1B deletion also improved survival in
      a cecal ligation puncture model of sepsis. CONCLUSIONS: PTP1B gene deletion
      protects against septic shock-induced cardiovascular dysfunction and mortality,
      and this may be the result of the profound reduction of cardiovascular
      inflammation. PTP1B is an attractive target for the treatment of sepsis.

PMID- 24578380
TI  - Identification and initial functional characterization of a human vascular cell
      enriched long noncoding RNA.
AB  - OBJECTIVE: Long noncoding RNAs (lncRNAs) represent a rapidly growing class of RNA
      genes with functions related primarily to transcriptional and post
      transcriptional control of gene expression. There is a paucity of information
      about lncRNA expression and function in human vascular cells. Thus, we set out to
      identify novel lncRNA genes in human vascular smooth muscle cells and to gain
      insight into their role in the control of smooth muscle cell phenotypes. APPROACH
      AND RESULTS: RNA sequencing (RNA-seq) of human coronary artery smooth muscle
      cells revealed 31 unannotated lncRNAs, including a vascular cell-enriched lncRNA
      (Smooth muscle and Endothelial cell-enriched migration/differentiation-associated
      long NonCoding RNA [SENCR]). Strand-specific reverse transcription polymerase
      chain reaction (PCR) and rapid amplification of cDNA ends indicate that SENCR is
      transcribed antisense from the 5' end of the FLI1 gene and exists as 2 splice
      variants. RNA fluorescence in situ hybridization and biochemical fractionation
      studies demonstrate SENCR is a cytoplasmic lncRNA. Consistent with this
      observation, knockdown studies reveal little to no cis-acting effect of SENCR on
      FLI1 or neighboring gene expression. RNA-seq experiments in smooth muscle cells
      after SENCR knockdown disclose decreased expression of Myocardin and numerous
      smooth muscle contractile genes, whereas several promigratory genes are
      increased. Reverse transcription PCR and Western blotting experiments validate
      several differentially expressed genes after SENCR knockdown. Loss-of-function
      studies in scratch wound and Boyden chamber assays support SENCR as an inhibitor
      of smooth muscle cell migration. CONCLUSIONS: SENCR is a new vascular cell
      enriched, cytoplasmic lncRNA that seems to stabilize the smooth muscle cell
      contractile phenotype.

PMID- 24578384
TI  - Overexpression of c1q/tumor necrosis factor-related protein-3 promotes phosphate
      induced vascular smooth muscle cell calcification both in vivo and in vitro.
AB  - OBJECTIVE: Vascular calcification is highly correlated with increased
      cardiovascular morbidity and mortality. C1q/tumor necrosis factor-related protein
      3 (CTRP3) is a newly identified adipokine that plays important roles in
      cardiovascular system. Here, we investigated the role of CTRP3 in vascular
      calcification and its underlying mechanism. APPROACH AND RESULTS: Adenine-induced
      chronic renal failure rat model was used to mimic the process of arterial medial
      calcification. The level of CTRP3 was elevated in serum and abdominal aorta of
      chronic renal failure rats. Periadventitial gene delivery of CTRP3 significantly
      accelerated the calcification of abdominal aorta and arterial ring. In cultured
      vascular smooth muscle cells (VSMCs), CTRP3 increased beta-glycerophosphate
      induced calcium deposition and alkaline phosphatase activity. Although CTRP3
      alone was not sufficient to induce calcification in VSMCs, it upregulated the
      expression of osteogenic marker genes including runt-related transcription factor
      2 (Runx2), bone morphogenetic protein 2, and osteopontin. CTRP3 further enhanced
      beta-glycerophosphate-induced downregulation of smooth muscle alpha-actin and
      smooth muscle 22alpha, while augmenting osteogenic marker expression in VSMCs
      induced by beta-glycerophosphate. In contrast, knockdown of CTRP3 in VSMCs
      potently suppressed beta-glycerophosphate-induced calcification. Mechanistically,
      knockdown of Runx2 inhibited CTRP3-promoted VSMC calcification. CTRP3 increased
      extracellular signal-regulated kinase 1/2 phosphorylation and reactive oxygen
      species production. Preincubation with U0126, an extracellular signal-regulated
      kinase 1/2 upstream kinase inhibitor, had no effect on CTRP3-induced reactive
      oxygen species production. However, pretreatment with N-acetyl-l-cysteine, a
      reactive oxygen species scavenger, suppressed CTRP3-induced extracellular signal
      regulated kinase 1/2 phosphorylation. Both N-acetyl-l-cysteine and U0126
      significantly inhibited CTRP3-induced upregulation of Runx2 and calcified nodule
      formation. CONCLUSIONS: CTRP3 promotes vascular calcification by enhancing
      phosphate-induced osteogenic transition of VSMC through reactive oxygen species
      extracellular signal-regulated kinase 1/2-Runx2 pathway.

PMID- 24578379
TI  - Genome-wide association study for circulating tissue plasminogen activator levels
      and functional follow-up implicates endothelial STXBP5 and STX2.
AB  - OBJECTIVE: Tissue plasminogen activator (tPA), a serine protease, catalyzes the
      conversion of plasminogen to plasmin, the major enzyme responsible for endogenous
      fibrinolysis. In some populations, elevated plasma levels of tPA have been
      associated with myocardial infarction and other cardiovascular diseases. We
      conducted a meta-analysis of genome-wide association studies to identify novel
      correlates of circulating levels of tPA. APPROACH AND RESULTS: Fourteen cohort
      studies with tPA measures (N=26 929) contributed to the meta-analysis. Three loci
      were significantly associated with circulating tPA levels (P<5.0*10(-8)). The
      first locus is on 6q24.3, with the lead single nucleotide polymorphism (SNP;
      rs9399599; P=2.9*10(-14)) within STXBP5. The second locus is on 8p11.21. The lead
      SNP (rs3136739; P=1.3*10(-9)) is intronic to POLB and <200 kb away from the tPA
      encoding the gene PLAT. We identified a nonsynonymous SNP (rs2020921) in modest
      linkage disequilibrium with rs3136739 (r(2)=0.50) within exon 5 of PLAT
      (P=2.0*10(-8)). The third locus is on 12q24.33, with the lead SNP (rs7301826;
      P=1.0*10(-9)) within intron 7 of STX2. We further found evidence for the
      association of lead SNPs in STXBP5 and STX2 with expression levels of the
      respective transcripts. In in vitro cell studies, silencing STXBP5 decreased the
      release of tPA from vascular endothelial cells, whereas silencing STX2 increased
      the tPA release. Through an in silico lookup, we found no associations of the 3
      lead SNPs with coronary artery disease or stroke. CONCLUSIONS: We identified 3
      loci associated with circulating tPA levels, the PLAT region, STXBP5, and STX2.
      Our functional studies implicate a novel role for STXBP5 and STX2 in regulating
      tPA release.

PMID- 24578386
TI  - Ethics support in institutional elderly care: a review of the literature.
AB  - Clinical ethics support mechanisms in healthcare are increasing but little is
      known about the specific developments in elderly care. The aim of this paper is
      to present a systematic literature review on the characteristics of existing
      ethics support mechanisms in institutional elderly care. A review was performed
      in three electronic databases (Pubmed, CINAHL/PsycINFO, Ethxweb). Sixty papers
      were included in the review. The ethics support mechanisms are classified in four
      categories: 'institutional bodies' (ethics committee and consultation team);
      'frameworks' (analytical tools to assist care professionals); 'educational
      programmes and moral case deliberation'; and 'written documents and policies'.
      For each category the goals, methods and ways of organising are described. Ethics
      support often serves several goals and can be targeted at various levels: case,
      professional or organisation. Over the past decades a number of changes have
      taken place in the development of ethics support in elderly care. Considering the
      goals, ethics support has become more outreaching and proactive, aiming to
      qualify professionals to integrate ethics in daily care processes. The approaches
      in clinical ethics support have become more diverse, more focused on everyday
      ethical issues and better adapted to the concrete learning style of the nursing
      staff. Ethics support has become less centrally organised and more connected to
      local contexts and primary process within the organisation. 

PMID- 24578387
TI  - Successful antegrade revascularization by the innovation of composite core dual
      coil in a three-vessel total occlusive disease for cardiac arrest patient using
      extracorporeal membrane oxygenation.

PMID- 24578385
TI  - The Vac14-interaction network is linked to regulators of the endolysosomal and
      autophagic pathway.
AB  - The scaffold protein Vac14 acts in a complex with the lipid kinase PIKfyve and
      its counteracting phosphatase FIG4, regulating the interconversion of
      phosphatidylinositol-3-phosphate to phosphatidylinositol-3,5-bisphosphate.
      Dysfunctional Vac14 mutants, a deficiency of one of the Vac14 complex components,
      or inhibition of PIKfyve enzymatic activity results in the formation of large
      vacuoles in cells. How these vacuoles are generated and which processes are
      involved are only poorly understood. Here we show that ectopic overexpression of
      wild-type Vac14 as well as of the PIKfyve-binding deficient Vac14 L156R mutant
      causes vacuoles. Vac14-dependent vacuoles and PIKfyve inhibitor-dependent
      vacuoles resulted in elevated levels of late endosomal, lysosomal, and autophagy
      associated proteins. However, only late endosomal marker proteins were bound to
      the membranes of these enlarged vacuoles. In order to decipher the linkage
      between the Vac14 complex and regulators of the endolysosomal pathway, a protein
      affinity approach combined with multidimensional protein identification
      technology was conducted, and novel molecular links were unraveled. We found and
      verified the interaction of Rab9 and the Rab7 GAP TBC1D15 with Vac14. The
      identified Rab-related interaction partners support the theory that the
      regulation of vesicular transport processes and phosphatidylinositol-modifying
      enzymes are tightly interconnected. 

PMID- 24578388
TI  - Cardiac magnetic resonance imaging to detect non-contiguous scar following atrial
      fibrillation ablation: identifying our knowledge gaps.

PMID- 24578390
TI  - Cardiopulmonary complications of end-stage renal disease and severe refractory
      hyperparathyroidism.

PMID- 24578389
TI  - Tumour necrosis factor-alpha participates on the endothelin-1/nitric oxide
      imbalance in small arteries from obese patients: role of perivascular adipose
      tissue.
AB  - AIMS: We assessed the impact of vascular and perivascular tumour necrosis factor
      alpha (TNF-alpha) on the endothelin (ET)-1/nitric oxide (NO) system and the
      molecular pathways involved in small arteries from visceral fat of obese patients
      (Obese) and Controls. METHODS AND RESULTS: Isolated small arteries from 16 Obese
      and 14 Controls were evaluated on a pressurized micromyograph. Endogenous ET-1
      activity was assessed by the ETA blocker BQ-123. TNF-alpha and NO were tested by
      anti-TNF-alpha infliximab (IFX) and N(omega)-nitro-l-arginine methylester (L
      NAME). Gene and protein expression of TNF-alpha, ET-1, ETA, and ETB receptors
      were determined by RT-PCR and IHC on arterial wall and in isolated adipocytes.
      Obese showed a blunted L-NAME-induced vasoconstriction, which was potentiated by
      IFX, and an increased relaxation to BQ-123, unaffected by L-NAME but attenuated
      by IFX. Perivascular adipose tissue (PVAT) removal reversed these effects. Obese
      showed intravascular superoxide excess, which was decreased by apocynin (NAD(P)H
      oxidase inhibitor), L-NAME, and BQ-123 incubations, and abolished by IFX. An
      increased vascular expression of ET-1, ETA, and ETB receptors, and higher
      vascular/perivascular TNF-alpha and TNF-alpha receptor expression were also
      detected. The arterial expression and phosphorylation of c-Jun N-terminal kinase
      (JNK) were higher in Obese vs. Controls, and downregulated by IFX. CONCLUSIONS:
      In small arteries of Obese, PVAT-derived TNF-alpha excess, and an increased
      vascular expression of ET-1 and ETA receptor, contribute to the ET-1/NO system
      imbalance, by impairing tonic NO release. Reactive oxygen species excess, via
      NAD(P)H oxidase activation, induces the endothelial nitric oxide synthase
      uncoupling, which in turn generates superoxide and impairs NO production. The up
      regulated JNK pathway represents a crucial molecular signalling involved in this
      process.

PMID- 24578391
TI  - Multiparametric assessment of myocarditis using simultaneous positron emission
      tomography/magnetic resonance imaging.

PMID- 24578393
TI  - Multiple disadvantaged statuses and health: the role of multiple forms of
      discrimination.
AB  - The double disadvantage hypothesis predicts that adults who hold more than one
      disadvantaged status may experience worse health than their singly disadvantaged
      and privileged counterparts. Research that has tested this thesis has yielded
      mixed findings due partly to a failure to examine the role of discrimination.
      This article uses data from the National Survey of Midlife Development in the
      United States (N = 2,647) to investigate the relationship between multiple
      disadvantaged statuses and health, and whether multiple forms of interpersonal
      discrimination contribute to this association. The results suggest that multiply
      disadvantaged adults are more likely to experience major depression, poor
      physical health, and functional limitations than their singly disadvantaged and
      privileged counterparts. Further, multiple forms of discrimination partially
      mediate the relationship between multiple stigmatized statuses and health. Taken
      together, these findings suggest that multiply disadvantaged adults do face a
      "double disadvantage" in health, in part, because of their disproportionate
      exposure to discrimination. 

PMID- 24578394
TI  - Race, gender, and chains of disadvantage: childhood adversity, social
      relationships, and health.
AB  - We use a life course approach to guide an investigation of relationships and
      health at the nexus of race and gender. We consider childhood as a sensitive
      period in the life course, during which significant adversity may launch chains
      of disadvantage in relationships throughout the life course that then have
      cumulative effects on health over time. Data from a nationally representative
      panel study (Americans' Changing Lives, N = 3,477) reveal substantial disparities
      between black and white adults, especially pronounced among men, in the quality
      of close relationships and in the consequences of these relationships for health.
      Greater childhood adversity helps to explain why black men have worse health than
      white men, and some of this effect appears to operate through childhood
      adversity's enduring influence on relationship strain in adulthood. Stress that
      occurs in adulthood plays a greater role than childhood adversity in explaining
      racial disparities in health among women. 

PMID- 24578396
TI  - Caught in a bad romance: adolescent romantic relationships and mental health.
AB  - Integrating insights from cultural sociology and identity theory, I explore the
      mental health consequences of adolescent romantic relationship inauthenticity-
      incongruence between thoughts/feelings and actions within romantic contexts.
      Applying sequence analysis to National Longitudinal Study of Adolescent Health
      data, I measure relationship inauthenticity by quantifying the extent to which
      the ordering of events of actual romantic relationships (e.g., holding hands,
      saying "I love you") diverges from the sequence of events within idealized
      relationship scripts among 5,316 adolescents. I then test its association with
      severe depression, suicide ideation, and suicide attempt. I find that romantic
      relationship inauthenticity is positively associated with the risk of all three
      markers of poor mental health, but only for girls. This study highlights the
      importance of gender and culture in determining how early romantic involvement
      influences psychological well-being.

PMID- 24578395
TI  - Intimate partner violence and depressive symptoms during adolescence and young
      adulthood.
AB  - Using longitudinal data from the Toledo Adolescent Relationships Study, we
      examine the relationship between intimate partner violence (IPV) and depressive
      symptoms during adolescence and young adulthood (N = 1,273) while controlling for
      time-stable and time-varying correlates. Results show temporal changes in
      depressive symptoms, such that increases in depressive symptoms correspond to IPV
      exposure. While prior work has theorized that certain populations may be at
      increased psychological vulnerability from IPV, results indicate that both
      perpetration and victimization are associated with increases in depressive
      symptoms for both men and women, and irrespective of whether IPV exposure
      occurred in adolescence or young adulthood. Cumulative exposure to IPV does not
      appear to increase depressive symptoms beyond the effect observed for the most
      recent IPV exposure, but physical maltreatment by a parent does appear to
      diminish the association between IPV perpetration and depressive symptoms for a
      small subset of the sample. 

PMID- 24578397
TI  - Reevaluating the "subjective weathering" hypothesis: subjective aging, coping
      resources, and the stress process.
AB  - The subjective weathering model contends that subjective aging is a key component
      of the stress process. This study reevaluates and extends this model by
      considering how adaptive capacities influence subjective aging and depressive
      symptoms in late adolescence and young adulthood. Using longitudinal data from
      the National Longitudinal Study of Adolescent Health (n = 7,230), I investigate
      how earlier stressors and coping resources contribute to older age identities
      (ages 18-22) and how these self-perceptions influence subsequent depressive
      symptoms (ages 25-29). The results show that subjective weathering alone does not
      lead to depressive symptoms; the critical issue is the level of psychosocial
      maturity that accompanies an older age identity. Those with high levels of
      psychosocial maturity, regardless of subjective age, were least likely to exhibit
      depressive symptoms. These results demonstrate that psychosocial maturity is an
      important adaptive resource that can shield young adults from the negative
      effects of "subjective weathering" or growing up fast. 

PMID- 24578399
TI  - Why do hospitals comply with federal regulation and what does it mean for
      variation in the U.S. health care system? Policy brief.

PMID- 24578398
TI  - The interplay between child and maternal health: reciprocal relationships and
      cumulative disadvantage during childhood and adolescence.
AB  - While many studies use parental socioeconomic status and health to predict
      children's health, this study examines the interplay over time between child and
      maternal health across childhood and adolescence. Using data from women in the
      National Longitudinal Study of Youth 1979 cohort and their children (N = 2,225),
      autoregressive cross-lagged models demonstrate a reciprocal relationship between
      child activity limitations and maternal health limitations in direct effects of
      child activity limitations on maternal health limitations two years later and
      vice versa-net of a range of health-relevant time-varying and time-invariant
      covariates. Furthermore, there are indirect effects of child activity limitations
      on subsequent maternal health limitations and indirect effects of maternal health
      limitations on subsequent child activity limitations via intervening health
      statuses. This study examines how the interplay between child and maternal health
      unfolds over time and describes how these interdependent statuses jointly
      experience health disadvantages. 

PMID- 24578400
TI  - Institutionalizing HIPAA compliance: organizations and competing logics in U.S.
      health care.
AB  - Health care in the United States is highly regulated, yet compliance with
      regulations is variable. For example, compliance with two rules for securing
      electronic health information in the 1996 Health Insurance Portability and
      Accountability Act took longer than expected and was highly uneven across U.S.
      hospitals. We analyzed 3,321 medium and large hospitals using data from the 2003
      Health Information and Management Systems Society Analytics Database. We find
      that organizational strategies and institutional environments influence hospital
      compliance, and further that institutional logics moderate the effect of some
      strategies, indicating the interplay of regulation, institutions, and
      organizations that contribute to the extensive variation that characterizes the
      U.S. health care system. Understanding whether and how health care organizations
      like hospitals respond to new regulation has important implications both for
      creating desired health care reform and for medical sociologists interested in
      the changing organizational structure of health care. 

PMID- 24578401
TI  - Derivative processes for modelling metabolic fluxes.
AB  - MOTIVATION: One of the challenging questions in modelling biological systems is
      to characterize the functional forms of the processes that control and
      orchestrate molecular and cellular phenotypes. Recently proposed methods for the
      analysis of metabolic pathways, for example, dynamic flux estimation, can only
      provide estimates of the underlying fluxes at discrete time points but fail to
      capture the complete temporal behaviour. To describe the dynamic variation of the
      fluxes, we additionally require the assumption of specific functional forms that
      can capture the temporal behaviour. However, it also remains unclear how to
      address the noise which might be present in experimentally measured metabolite
      concentrations. RESULTS: Here we propose a novel approach to modelling metabolic
      fluxes: derivative processes that are based on multiple-output Gaussian processes
      (MGPs), which are a flexible non-parametric Bayesian modelling technique. The
      main advantages that follow from MGPs approach include the natural non-parametric
      representation of the fluxes and ability to impute the missing data in between
      the measurements. Our derivative process approach allows us to model changes in
      metabolite derivative concentrations and to characterize the temporal behaviour
      of metabolic fluxes from time course data. Because the derivative of a Gaussian
      process is itself a Gaussian process, we can readily link metabolite
      concentrations to metabolic fluxes and vice versa. Here we discuss how this can
      be implemented in an MGP framework and illustrate its application to simple
      models, including nitrogen metabolism in Escherichia coli. AVAILABILITY AND
      IMPLEMENTATION: R code is available from the authors upon request.

PMID- 24578402
TI  - ngsCAT: a tool to assess the efficiency of targeted enrichment sequencing.
AB  - MOTIVATION: Targeted enrichment sequencing by next-generation sequencing is a
      common approach to interrogate specific loci or the whole exome in the human
      genome. The efficiency and the lack of bias in the enrichment process need to be
      assessed as a quality control step before performing downstream analysis of the
      sequence data. Tools that can report on the sensitivity, specificity, uniformity
      and other enrichment-specific features are needed. RESULTS: We have implemented
      the next-generation sequencing data Capture Assessment Tool (ngsCAT), a tool that
      takes the information of the mapped reads and the coordinates of the targeted
      regions as input files, and generates a report with metrics and figures that
      allows the evaluation of the efficiency of the enrichment process. The tool can
      also take as input the information of two samples allowing the comparison of two
      different experiments. AVAILABILITY AND IMPLEMENTATION: Documentation and
      downloads for ngsCAT can be found at http://www.bioinfomgp.org/ngscat.

PMID- 24578403
TI  - LASAGNA-Search 2.0: integrated transcription factor binding site search and
      visualization in a browser.
AB  - LASAGNA-Search 2.0 is an integrated webtool for transcription factor (TF) binding
      site search and visualization. The tool is based on the LASAGNA (Length-Aware
      Site Alignment Guided by Nucleotide Association) algorithm. It eliminates manual
      TF model collection and promoter sequence retrieval. Search results can be
      visualized locally or in the University of California Santa Cruz Genome Browser.
      Gene regulatory network inference based on the search results offers another way
      of visualization. A list of TFs and target genes is all a user needs to start
      using the tool. LASAGNA-Search 2.0 currently offers 1792 TF models and supports
      15 species for automatic promoter retrieval and visualization in the University
      of California Santa Cruz Genome Browser. It is a user-friendly tool designed for
      non-bioinformaticians and is suitable for research and teaching. We describe
      important changes made since the initial release. AVAILABILITY AND
      IMPLEMENTATION: LASAGNA-Search 2.0 is freely available without registration at
      http://biogrid.engr.uconn.edu/lasagna_search/.

PMID- 24578404
TI  - Accurate computational prediction of the transcribed strand of CRISPR non-coding
      RNAs.
AB  - MOTIVATION: CRISPR RNAs (crRNAs) are a type of small non-coding RNA that form a
      key part of an acquired immune system in prokaryotes. Specific prediction methods
      find crRNA-encoding loci in nearly half of sequenced bacterial, and three
      quarters of archaeal, species. These Clustered Regularly Interspaced Short
      Palindromic Repeats (CRISPR) arrays consist of repeat elements alternating with
      specific spacers. Generally one strand is transcribed, producing long pre-crRNAs,
      which are processed to short crRNAs that base pair with invading nucleic acids to
      facilitate their destruction. No current software for the discovery of CRISPR
      loci predicts the direction of crRNA transcription. RESULTS: We have developed an
      algorithm that accurately predicts the strand of the resulting crRNAs. The method
      uses as input CRISPR repeat predictions. CRISPRDirection uses parameters that are
      calculated from the CRISPR repeat predictions and flanking sequences, which are
      combined by weighted voting. The prediction may use prior coding sequence
      annotation but this is not required. CRISPRDirection correctly predicted the
      orientation of 94% of a reference set of arrays. AVAILABILITY AND IMPLEMENTATION:
      The Perl source code is freely available from
      http://bioanalysis.otago.ac.nz/CRISPRDirection.

PMID- 24578405
TI  - Single-centre experience with next-generation devices for transapical aortic
      valve implantation.
AB  - OBJECTIVES: Transcatheter aortic valve implantation (TAVI) has become an
      established procedure in patients with aortic stenosis and high surgical risk.
      Experience with first-generation transcatheter heart valves (THVs) is broad but
      limitations, e.g. paravalvular regurgitation, have been demonstrated. Much hope
      rests on the recently Conformite Europeenne mark approved next-generation devices
      to improve results in these patients. However, apart from the initial approval
      studies, clinical data with these new devices are still scarce. We aimed to
      assess short-term outcomes of 200 consecutive patients who underwent transapical
      TAVI with next-generation THV at our institution. METHODS: Transapical TAVI was
      performed in 200 consecutive patients 80.5+/-6.7 years old (38.5% female) at high
      surgical risk (log EuroSCORE 20.2+/-16.5%). Devices implanted were the Engager
      (Medtronic, Inc., Minneapolis, MN, USA; n=50), JenaValve (JenaValve Technology,
      Munich, Germany; n=88) and Symetis Acurate (Symetis SA, Ecublens, Switzerland;
      n=62) THV that were selected by the heart team on an individual basis. Data at
      baseline, during the procedure and follow-up were analysed according to
      standardized Valve Academic Research Consortium end points. Median follow-up was
      219 days. RESULTS: Implantation was successful in 96.5% of cases. Valve function
      improved significantly with an increase in effective orifice area from 0.8+/-0.4
      to 1.8+/-0.3 cm2 and a reduction in mean transvalvalvular gradients from 34.0+/
      17.0 to 11.2+/-5.4 mmHg. Paravalvular regurgitation was none or trace in 70.3% of
      patients, Grade 1 in 26.1%, and Grade 2 in 3.5%. No patients developed aortic
      regurgitation>Grade 2. Major access site complications occurred in 6.5%, major
      stroke in 1.5% and stage-3 kidney injury in 2.5% of patients. A permanent
      pacemaker was implanted in 20.5% of patients overall and in 8.0% for a complete
      heart block. At 30-day follow-up 72.8% of patients were in New York Heart
      Association class I or II (10.5% at baseline). Overall survival was 91.5% at 30
      days and 73.9% at 1 year. CONCLUSIONS: In a real-world clinical setting, next
      generation transapical THV yielded positive haemodynamic results. The incidence
      of relevant paravalvular regurgitation was scarce in this group and clinical
      outcomes were encouraging during short-term follow-up. Long-term follow-up is
      required to investigate the durability of these new devices.

PMID- 24578406
TI  - Unusual complication of neurofibromatosis.

PMID- 24578407
TI  - Revised ESTS guidelines for preoperative mediastinal lymph node staging for non
      small-cell lung cancer.
AB  - Accurate preoperative staging and restaging of mediastinal lymph nodes in
      patients with potentially resectable non-small-cell lung cancer (NSCLC) is of
      paramount importance. In 2007, the European Society of Thoracic Surgeons (ESTS)
      published an algorithm on preoperative mediastinal staging integrating imaging,
      endoscopic and surgical techniques. In 2009, the International Association for
      the Study of Lung Cancer (IASLC) introduced a new lymph node map. Some changes in
      this map have an important impact on mediastinal staging. Moreover, more evidence
      of the different mediastinal staging technique has become available. Therefore, a
      revision of the ESTS guidelines was needed. In case of computed tomography (CT)
      enlarged or positron emission tomography (PET)-positive mediastinal lymph nodes,
      tissue confirmation is indicated. Endosonography [endobronchial ultrasonography
      (EBUS)/esophageal ultrasonography (EUS)] with fine-needle aspiration (FNA) is the
      first choice (when available), since it is minimally invasive and has a high
      sensitivity to rule in mediastinal nodal disease. If negative, surgical staging
      with nodal dissection or biopsy is indicated. Video-assisted mediastinoscopy is
      preferred to mediastinoscopy. The combined use of endoscopic staging and surgical
      staging results in the highest accuracy. When there are no enlarged lymph nodes
      on CT and when there is no uptake in lymph nodes on PET or PET-CT, direct
      surgical resection with systematic nodal dissection is indicated for tumours <= 3
      cm located in the outer third of the lung. In central tumours or N1 nodes,
      preoperative mediastinal staging is indicated. The choice between endoscopic
      staging with EBUS/EUS and FNA or video-assisted mediastinoscopy depends on local
      expertise to adhere to minimal requirements for staging. For tumours >3 cm,
      preoperative mediastinal staging is advised, mainly in adenocarcinoma with high
      standardized uptake value. For restaging, invasive techniques providing
      histological information are advisable. Both endoscopic techniques and surgical
      procedures are available, but their negative predictive value is lower compared
      with the results obtained in baseline staging. An integrated strategy using
      endoscopic staging techniques to prove mediastinal nodal disease and
      mediastinoscopy to assess nodal response after induction therapy needs further
      study.

PMID- 24578409
TI  - The extracardiac conduit Fontan procedure in Australia and New Zealand:
      hypoplastic left heart syndrome predicts worse early and late outcomes.
AB  - OBJECTIVES: To identify factors associated with hospital and long-term outcomes
      in a binational cohort of extracardiac conduit (ECC) Fontan recipients. METHODS:
      All patients who underwent an ECC Fontan procedure from 1997 to 2010 in Australia
      and New Zealand were identified, and perioperative, follow-up, echocardiographic
      and reintervention data collected. Risk factors for early and late mortality,
      failure and adverse outcomes were analysed. RESULTS: A total of 570 patients were
      identified, and late follow-up was available in 529 patients. The mean follow-up
      was 6.7 years (standard deviation: 3.5) and completeness of the follow-up was
      98%. There were seven hospital mortalities (1%) and 21 patients (4%) experienced
      early failure (death, Fontan takedown/revision or mechanical circulatory
      support). Prolonged length of stay occurred in 10% (57 patients), and prolonged
      effusions in 9% (51 patients). Overall survival at 14 years was 96% (95%
      confidence interval [CI]: 93-98%), and late survival for patients discharged with
      intact Fontan was 98% (95% CI: 94-99%). The rates of late failure (late death,
      transplantation, takedown, New York Heart Association class III/IV or protein
      losing enteropathy) and adverse events (late failure, reoperation, percutaneous
      intervention, pacemaker, thromboembolic event or supraventricular tachycardia)
      per 100 patient-years were 0.8 and 3.8, and their 14-year freedoms were 83% (95%
      CI: 70-91%) and 53% (95% CI: 41-64%), respectively. After adjustment for
      confounders, hypoplastic left heart syndrome (HLHS) was strongly associated with
      prolonged effusions (OR: 2.9, 95% CI: 1.4-5.9), late failure (hazard ratio [HR]:
      2.8, 95% CI: 1.1-7.5) and adverse events (HR: 3.6, 95% CI: 1.3-7.5). CONCLUSIONS:
      The extracardiac Fontan procedure provides excellent survival into the second
      decade of life, but half of patients will suffer a late adverse event by 14
      years. Patients with HLHS are at higher risk of late adverse events than other
      morphological groups, but their survival is still excellent.

PMID- 24578410
TI  - Simultaneous mobile thrombi of the aortic valve and thoracic aorta.

PMID- 24578408
TI  - Deep hypothermic circulatory arrest versus non-deep hypothermic beating heart
      strategy in descending thoracic or thoracoabdominal aortic surgery.
AB  - OBJECTIVES: The ideal cardiopulmonary bypass (CPB) strategy during open surgical
      repair of the descending thoracic aorta (DTA) or thoracoabdominal aorta (TAA) is
      controversial. This study aimed to compare the clinical outcomes between deep
      hypothermic circulatory arrest (DHCA) and non-deep hypothermic beating heart CPB
      (non-DHCA) for DTA or TAA replacement. METHODS: From January 1994 to August 2011,
      259 patients underwent DTA or TAA replacement. Of these, 212, who were judged to
      be suitable for both DHCA (n = 79) and non-DHCA (n = 109), were analysed. In
      hospital outcomes were compared using propensity scores and inverse-probability
      weighting adjustment based on 20 preoperative variables to reduce treatment
      selection bias. RESULTS: Early mortality was 12.7% in the DHCA group and 7.5% in
      the non-DHCA group (P = 0.23). Major adverse outcomes included stroke in 13
      patients (6.1%), paraplegia in 10 (4.7%), low cardiac output syndrome (LCOS) in
      17 (8.0%) and multiorgan failure in 12 (5.7%). After adjustment, patients who
      underwent DHCA were at a risk of death (odds ratio (OR), 1.86; P = 0.18) and
      permanent neurological injury (OR, 1.06; P = 0.90) similar to that of those who
      underwent non-DHCA, but at greater risk of LCOS (OR, 3.85; P = 0.012).
      Furthermore, prolonged ventilator support (>24 h) was more frequent with DHCA
      than with non-DHCA (OR, 2.33; P = 0.004). CONCLUSIONS: Compared with non-DHCA,
      DHCA was associated with greater risk of postoperative LCOS and prolonged
      ventilator support. Therefore, non-DHCA seems to be a more appropriate option
      than DHCA for open DTA/TAA repair whenever the aortic anatomy lends itself to
      this approach.

PMID- 24578411
TI  - Mechanical cardiac support in children with congenital heart disease with
      intention to bridge to heart transplantation?.
AB  - OBJECTIVES: A significant number of children affected by congenital heart disease
      (CHD) develop heart failure early or late after surgery, and heart
      transplantation (OHTx) remains the last treatment option. Due to shortage of
      donor organs in paediatric group, mechanical circulatory support (MCS) is now
      routinely applied as bridging strategy to increase survival on the waiting list
      for OTHx. We sought to assess the impact of MCS as intention to bridge to OHTx in
      patients with CHD less than 16 years of age. METHODS: From 1998 to 2013, 106
      patients received 113 episodes of MCS with paracorporeal devices as intention to
      bridge to OHTx. Twenty-nine had CHD, 15 (52%) with two-ventricle (Group A) and 14
      (48%) with single-ventricle physiology (Group B). In Group A, 5 children had
      venoarterial extracorporeal membrane oxygenation (VA ECMO), 6 left ventricular
      assist device (LVAD), 2 biventricular assist device (BIVAD), 1 VA ECMO followed
      by BIVAD and 1 BIVAD followed by VA ECMO. In Group B, VA ECMO was used in 7
      children, univentricular assist device (UVAD) changed to VA ECMO in 4, UVAD in 2
      and surgical conversion to two-ventricles physiology with BIVAD support changed
      to VA ECMO in 1. RESULTS: Twenty-one of 29 (72%) children survived to
      recovery/OHTx. Seven of 29 (59%) survived to discharge. In Group A, 11/15 (73%)
      survived to recovery/OHTx and 9/15 (60%) survived to discharge. Four of 15 (27%)
      died awaiting OHTx. One child had graft failure requiring VA ECMO and was bridged
      successfully to retransplantation. One child dying after OHTx had acute
      rejection, was supported with VA ECMO and then BIVAD but did not recover. One
      patient had an unsuccessful second run on BIVAD 1 year after recovery from VA
      ECMO. In Group B, 10/14 (71%) survived to recovery/OHTx and 8/14 (57%) survived
      to discharge. Four of 14 (29%) died awaiting OHTx. Of deaths after OHTx, 1
      occurred intraoperatively and 1 was consequent to graft failure and had an
      unsuccessful second run with VA ECMO. CONCLUSIONS: Children with CHD can be
      successfully bridged with MCS to heart transplantation. Single-ventricle
      circulation compared with biventricular physiology does not increase the risk of
      death before transplant or before hospital discharge.

PMID- 24578412
TI  - Anomalous circumflex origin from the right coronary artery forming 'bleb sign' in
      transoesophageal echocardiography.

PMID- 24578413
TI  - Assessment of the myocardium with cardiac computed tomography.
AB  - The imaging of myocardial disease is of increasing importance for cardiologists
      from all subspecialties, for diagnosis, risk stratification, or to facilitate
      therapy. While the gold standard modalities for such assessment are cardiac
      magnetic resonance and echocardiography, these are not universally suitable.
      Cardiac computed tomography (CT), well-established for the assessment of coronary
      artery disease (CAD), can be of value in the assessment of myocardial pathology,
      due to excellent patient compatibility and tolerability, high spatial resolution,
      and acceptable tissue characterization. This review considers the value and
      limitations of CT in the assessment of the myocardial sequelae of CAD, and for
      patients with a variety of other cardiomyopathic diseases, depicts some of the
      common findings, and considers current developments in this area. 

PMID- 24578414
TI  - The potential of research to inform theory, policy, and practice.

PMID- 24578417
TI  - Complete urethral transection.

PMID- 24578416
TI  - Prevalence of depressive disorders and related factors in women in the first
      trimester of their pregnancies in Erzurum, Turkey.
AB  - INTRODUCTION: Depression is the most frequently seen mental disease in the
      pregnancy period. The first trimester of pregnancy is important in terms of its
      effects on both the fetus and on the mother. This study has researched the
      prevalence of depression in women in the first trimester of their pregnancies in
      Erzurum, which is a large province in the Eastern region of Turkey. METHOD: The
      study participants were 463 pregnant women who were in the first trimester of
      their pregnancy. Screening was primarily carried out using the Edinburgh
      Postnatal Depression Scale (EPDS), and Structured Clinical Interview for
      Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition (DSM-IV)
      Clinical Version (SCID-I) was applied to those participants with a score of 12
      points and higher. To assess the risk factors, a sociodemographic data form was
      completed by the authors. RESULTS: The total depressive disorder rate was 16.8%
      in women in the first trimester of their pregnancies (12.3% major depressive
      disorder, 1.5% double depression, 2.6% minor depressive disorder and 0.4%
      dysthymia). A history of mental disease, mental disease suffered during a
      previous pregnancy, exposure to violence in the present pregnancy, an unplanned
      pregnancy and spouse's unemployment were predictors for depressive disorders.
      CONCLUSION: It is important to identify the risk groups for the early recognition
      of depression in pregnancy. Developing depression screening programs can be
      useful for early diagnosis and therapy.

PMID- 24578418
TI  - TB tendering must take account of quality, says BVA.

PMID- 24578415
TI  - Defects in GABA metabolism affect selective autophagy pathways and are alleviated
      by mTOR inhibition.
AB  - In addition to key roles in embryonic neurogenesis and myelinogenesis, gamma
      aminobutyric acid (GABA) serves as the primary inhibitory mammalian
      neurotransmitter. In yeast, we have identified a new role for GABA that augments
      activity of the pivotal kinase, Tor1. GABA inhibits the selective autophagy
      pathways, mitophagy and pexophagy, through Sch9, the homolog of the mammalian
      kinase, S6K1, leading to oxidative stress, all of which can be mitigated by the
      Tor1 inhibitor, rapamycin. To confirm these processes in mammals, we examined the
      succinic semialdehyde dehydrogenase (SSADH)-deficient mouse model that
      accumulates supraphysiological GABA in the central nervous system and other
      tissues. Mutant mice displayed increased mitochondrial numbers in the brain and
      liver, expected with a defect in mitophagy, and morphologically abnormal
      mitochondria. Administration of rapamycin to these mice reduced mTOR activity,
      reduced the elevated mitochondrial numbers, and normalized aberrant antioxidant
      levels. These results confirm a novel role for GABA in cell signaling and
      highlight potential pathomechanisms and treatments in various human pathologies,
      including SSADH deficiency, as well as other diseases characterized by elevated
      levels of GABA. 

PMID- 24578419
TI  - Vet struck off following convictions for wounding and false imprisonment.

PMID- 24578420
TI  - EC 'ready to act' against Russian ban on imports of live pigs and pork.

PMID- 24578421
TI  - FVE welcomes greater emphasis on disease prevention in animal health law.

PMID- 24578425
TI  - BVA warns of the dangers posed by receding flood waters.

PMID- 24578426
TI  - Partnership and collaboration key to controlling livestock diseases.

PMID- 24578427
TI  - Use of animal medicines in the food chain.

PMID- 24578429
TI  - Getting the message across in disease emergencies.

PMID- 24578430
TI  - Highlighting the potential benefits of dogs to families living with autism.

PMID- 24578431
TI  - Veterinary medicines: product update.
AB  - The following information has been produced for Veterinary Record by the
      Veterinary Medicines Directorate (VMD) to provide an update for veterinary
      surgeons on recent changes to marketing authorisations for veterinary medicines
      in the UK and on other relevant issues. 

PMID- 24578432
TI  - Acorn poisoning in cattle and sheep.
AB  - * Multiple cases of acorn poisoning in cattle and sheep following bumper crop *
      Salmonella Dublin infection causes abortions in cattle * Respiratory disease
      affecting different age groups of pigs on a nursery finisher unit * Porcine
      dermatitis and nephropathy syndrome cases diagnosed * A further case of suspect
      Marek's disease in turkeys. These are among matters discussed in the Animal
      Health and Veterinary Laboratories Agency's (AHVLA's) disease surveillance report
      for November 2013 to January 2014.

PMID- 24578433
TI  - Umbilical swellings in calves: a continuing challenge.

PMID- 24578435
TI  - Fatal spirocercosis in a free-ranging red fox.

PMID- 24578434
TI  - History of One Health and One Medicine.

PMID- 24578436
TI  - Canine distemper virus and badgers.

PMID- 24578445
TI  - Combined effects of physical illness and comorbid psychiatric disorder on risk of
      suicide in a national population study.
AB  - BACKGROUND: People with physical illness often have psychiatric disorder and this
      comorbidity may have a specific influence on their risk of suicide. AIMS: To
      examine how physical illness and psychiatric comorbidity interact to influence
      risk of suicide, with particular focus on relative timing of onset of the two
      types of illness. METHOD: Based on the national population of Denmark, individual
      level data were retrieved from five national registers on 27 262 suicide cases
      and 468 007 gender- and birth-date matched living controls. Data were analysed
      using conditional logistic regression. RESULTS: Both suicides and controls with
      physical illness more often had comorbid psychiatric disorder than their
      physically healthy counterparts. Although both physical and psychiatric illnesses
      constituted significant risk factors for suicide, their relative timing of onset
      in individuals with comorbidity significantly differentiated the associated risk
      of suicide. While suicide risk was highly elevated when onsets of both physical
      and psychiatric illness occurred close in time to each other, regardless which
      came first, psychiatric comorbidity developed some time after onset of physical
      illness exacerbated the risk of suicide substantially. CONCLUSIONS: Suicide risk
      in physically ill people varies substantially by presence of psychiatric
      comorbidity, particularly the relative timing of onset of the two types of
      illness. Closer collaboration between general and mental health services should
      be an essential component of suicide prevention strategies.

PMID- 24578446
TI  - Cannabis and stimulant disorders and readmission 2 years after first-episode
      psychosis.
AB  - BACKGROUND: Few studies have examined the impact of stimulant use on outcome in
      early psychosis. Ceasing substance use may lead to positive outcomes in
      psychosis. AIMS: To examine whether baseline cannabis or stimulant disorders and
      ongoing drug use predict readmission within 2 years of a first psychosis
      admission. METHOD: Predictors of readmission were examined with Cox regression in
      7269 people aged 15-29 years with a first psychosis admission. RESULTS: Baseline
      cannabis and stimulant disorders did not predict readmission. A stimulant
      disorder diagnosis prior to index psychosis admission predicted readmission, but
      a prior cannabis disorder diagnosis did not. Ongoing problem drug use predicted
      readmission. The lowest rate of readmission occurred in people whose baseline
      drug problems were discontinued. CONCLUSIONS: Prior admissions with stimulant
      disorder may be a negative prognostic sign in first-episode psychosis. Drug use
      diagnoses at baseline may be a good prognostic sign if they are identified and
      controlled.

PMID- 24578447
TI  - Morphological evaluation of the iliac and femoral arteries; possibilities and
      perspectives.
AB  - The study presented an approach to the morphometric image of atherosclerotic
      lesions of the final segment of the abdominal aorta, femoral and iliac arteries,
      considering possible endovascular intervention. The evaluation of these arteries
      is very important, because they are often used as a point of access for
      endovascular procedures performed on the peripheral arteries, or within the
      thoracic and abdominal aorta and its branches, as well as coronary arteries. The
      aim of the study was to determine morphometric measurements describing the
      atherosclerotic lesions, including the methodology of their surgical
      interpretation. MATERIAL AND METHODS: The study group comprised 128 tomograms of
      patients qualified for surgery. An algorithm based on the mathematical morphology
      was designed to track the vessels, starting from the division of the common
      femoral artery, and ending at the bifurcation of the abdominal aorta. We proposed
      a set of numerical measurements of the observed arterial changes. RESULTS AND
      CONCLUSIONS: We analysed 128 tomograms with a 94.5% efficiency, and with the
      assessment accuracy of the degree of lumen reduction (MAE--1.5%). We observed
      much higher measurement values of local tortuosity of the atherosclerotic
      arteries (0.3-1 radians), as compared to their anatomical course in a healthy
      subject (0-0.2 radians). The presented method can be a very accurate and useful
      tool in the numerical analysis of the lumen distribution of the arteries and
      atherosclerosis, dedicated to surgeons elaborating management strategies.

PMID- 24578444
TI  - Violent behaviour and post-traumatic stress disorder in US Iraq and Afghanistan
      veterans.
AB  - BACKGROUND: Violence towards others in the community has been identified as a
      significant problem for a subset of Iraq and Afghanistan veterans. AIMS: To
      investigate the extent to which post-traumatic stress disorder (PTSD) and other
      risk factors predict future violent behaviour in military veterans. METHOD: A
      national, multiwave survey enrolling a random sample of all US veterans who
      served in the military after 11 September 2001 was conducted. A total of 1090
      veterans from 50 US states and all military branches completed two survey waves
      mailed 1 year apart (retention rate = 79%). RESULTS: Overall, 9% endorsed
      engaging in severe violence and 26% in other physical aggression in the previous
      year, as measured at Wave 2. Younger age, financial instability, history of
      violence before military service, higher combat exposure, PTSD, and alcohol
      misuse at Wave 1 were significantly associated with higher severe violence and
      other physical aggression in the past year at Wave 2. When combinations of these
      risk factors were present, predicted probability of violence in veterans rose
      sharply. Veterans with both PTSD and alcohol misuse had a substantially higher
      rate of subsequent severe violence (35.9%) compared with veterans with alcohol
      misuse without PTSD (10.6%), PTSD without alcohol misuse (10.0%) or neither PTSD
      nor alcohol misuse (5.3%). Using multiple regression, we found that veterans with
      PTSD and without alcohol misuse were not at significantly higher risk of severe
      violence than veterans with neither PTSD nor alcohol misuse. There was a trend
      for other physical aggression to be higher in veterans with PTSD without alcohol
      misuse. CONCLUSIONS: Co-occurring PTSD and alcohol misuse was associated with a
      marked increase in violence and aggression in veterans. Compared with veterans
      with neither PTSD nor alcohol misuse, veterans with PTSD and no alcohol misuse
      were not significantly more likely to be severely violent and were only
      marginally more likely to engage in other physical aggression. Attention to
      cumulative effects of multiple risk factors beyond diagnosis--including
      demographics, violence history, combat exposure, and veterans' having money to
      cover basic needs like food, shelter, transportation, and medical care--is
      crucial for optimising violence risk management.

PMID- 24578448
TI  - VAAFT: a new minimally invasive method in the diagnostics and treatment of anal
      fistulas--initial results.
AB  - The aim of the study was to present our own experience in the treatment of anal
      fistulas by means of VAAFT (Video-Assisted Anal Fistula Treatment). MATERIAL AND
      METHODS: Twenty patients were qualified for the VAAFT procedure. All were
      subjected to diagnostics. Two patients after the diagnostic stage underwent
      classical fistula surgery. The remaining 18 patients were subjected to the full
      procedure (diagnostic fistuloscopy, supply of the internal ostium, and
      coagulation of the fistula canal). The mean observation period was 10 months.
      RESULTS: In most cases the trans-sphincter fistula was observed during the
      diagnostic phase, including three with additional fluid compartments. There was
      one intersphincteric fistula. Considering the 18 patients subjected to the full
      VAAFT procedure the internal ostium was supplied by means of an advancement flap
      in 3 cases, while in 11 by means of a mattress suture, including one with
      additional tissue glue. In 4 cases the internal ostium was tightly covered by
      mucosa. Surgical complications were not observed during the procedure. During
      further observation a permanent fistula was observed in 4 (22%) patients, and in
      two (17%), recurrence of anal fistula. In the remaining 12 patients one observed
      healing without fistula recurrence. Complications were not observed, including
      stool and gas control deterioration (based on the FISI scoring). CONCLUSIONS: The
      VAAFT method does not affect sphincter efficiency, no intra- and postoperative
      complications were observed. As compared to other minimally invasive procedures a
      comparable recovery rate is observed without the risk of incontinence. It is the
      only method enabling the intraoperative identification of the internal ostium and
      fistula canal under visual control. Initial optimistic results require further
      investigations on a larger group of patients.

PMID- 24578449
TI  - Effect of perioperative glutamine administration on C-reactive protein and liver
      function tests in patients undergoing hepatic resection.
AB  - Hepatic resections are commonly associated with high morbidity and mortality.
      Nutrition plays an important role in reducing postoperative complications besides
      improvement in intensive care and perioperative management. The aim of the study
      was to evaluate the role of glutamine as an immunonutrient in patients undergoing
      hepatic resection. MATERIAL AND METHODS: The study included 22 patients who
      underwent hepatectomy. Patients were randomized into two equal groups wherein
      group A patients received perioperative glutamine whereas group B patients served
      as controls. Primary outcome measures were level of serum albumin, C-reactive
      protein (CRP), liver function tests and absolute neutrophil counts in the
      postoperative period while secondary outcome included post operative
      complications. RESULTS: Glutamine decreased the CRP response in liver resection
      in a statistically significant manner (p=0.028) on the fifth post operative day.
      This may signify that glutamine decreases the post operative inflammatory
      response associated with liver resection. Glutamine did not have any significant
      effect on liver function tests. Postoperative morbidity was less in patients who
      received glutamine. CONCLUSION: Glutamine successfully blunted the CRP response
      in patients who received glutamine postoperatively. Decrease in morbidity
      following glutamine administration is an attractive area of prospective research
      and requires further consideration involving larger patient groups.

PMID- 24578450
TI  - Iatrogenic bile duct injuries--clinical problems.
AB  - Laparoscopic cholecystectomy is one of the most frequently performed surgical
      procedures in surgical wards. Iatrogenic bile duct injuries (IBDI) incurred
      during the procedures are among postoperative complications that are most
      difficult to treat. The risk of bile duct injury is 0.2-0.4%, and their
      consequences are unpleasant both for the surgeon and for the patient. The aim of
      the study was analysis of iatrogenic bile duct injuries and methods of their
      repair, taking into consideration the circumstances, under which the injuries
      occur. MATERIAL AND METHODS: The study group consisted of 16 patients who had
      suffered IBDI during surgery. The analysed parameters included sex, age,
      indications for surgery, the setting of the surgical procedure and the type of
      bile duct injury. Additionally, the time of injury diagnosis, type of repair and
      treatment outcome were assessed. The IBDI analysis used the EAES classification
      of injuries. The time of IBDI repair was defined as immediate, early or
      late,depending on the time that had passed from the injury. The analysis included
      complications seen after bile duct repair. RESULTS: The study group consisted of
      10 women and 6 men, aged 29-84. Patients underwent 6 classic cholecystectomies, 8
      laparoscopic cholecystectomies, one gastrotomy to remove oesophageal prosthesis
      and one laparotomy due to peptic ulcer. IBDI was diagnosed intraoperatively in 4
      patients. In 12 patients IBDI was diagnosed within 1-7 days. The diagnosis was
      based on endoscopic retrograde cholangiopancreatography and the results of
      biochemistry tests. According to the EAES classification, the injuries were of
      type 1 (4 patients), type 2 (8 patients), type 5 (3 patients) and type 6 (1
      patients). Reconstruction procedures were performed during the same anaesthesia
      session in 3 patients, and in the early period in 13 patients. The main procedure
      was Roux-en-Y anastomosis (12 patients), with the remaining including bile-duct
      suturing over a T-tube (3 patients) and underpinning of an accessory bile duct in
      the pocket left after gallbladder removal (1 patient). The most common
      reconstruction complications included bile leak (3 patients), recurrent
      cholangitis (3 patients) and bile duct stricture (2 patients). Mortality in the
      study group was 12.5%. CONCLUSIONS: The procedures of laparoscopic and classic
      cholecystectomy are associated with a risk of IBDI, especially in the presence of
      inflammatory state of the gall-bladder. IBDI is a complex complication: its
      treatment poses a challenge for the operating surgeon, and even the most careful
      treatment adversely affects the patient's lifedue to complications.

PMID- 24578451
TI  - Surgical site infection--the authors' own prospective research.
AB  - Surgical site infection is a common complication in surgery, which increases
      treatment cost, extends hospitalization time and can lead to septic
      complications. The aim of the study was analysis of postoperative infections in
      own material and finding significant risk factors with preserving the obligatory
      procedures in the clinic. MATERIAL AND METHODS: Prospective analysis of 270
      consecutively operated patients aged from 18 to 101 was performed with
      observation of early infection until 7th day postoperatively. Factors judged
      included: age, sex, BMI, operation type: elective or urgent, physical preparation
      for surgery, antibiotic prophylaxis, length and type of surgery. Wound
      observation card was used. Data were analysed statistically (t-Student's test,
      chi2 test, U Mann Whitney test and logistic regression analysis). RESULTS: Wound
      infection was observed in 33 patients (12.22% of the entire group). In 24 (8.88%)
      it was a superficial infection and in 9 (3.33%) deep infection. Statistically
      significant risk factors were age, presence of diabetes, operation time and
      operations on large bowel. The average age of patients with present infection was
      61.2. In the group without infection there were 6,3% patients with diabetes and
      20.8% in the group with infection. In our study diabetes increased the risk of
      infection four times. The longer the operation time the higher was the risk of
      deep infection (without complications 76.2 minutes, superficial 94.9 minutes,
      deep 148.9 minutes). Operations on large bowel were performed in 11.9%of all
      study patients. In the group of 33 patients with surgical wound infection, 39.4%
      had colon surgery, 39.4% of all deep infections and 29.2% of all superficial
      infections. CONCLUSIONS: In own study material significant risk factors of
      surgical wound infection were: age, presence of diabetes, length of operation,
      large bowel surgery. In preoperative course risk factors should be identified to
      perform certain prophylactic procedures to lower the risk of infectious
      complications.

PMID- 24578452
TI  - Anterior overlapping sphincteroplasty--who benefits from the surgery?
AB  - The aim of the study was to identify clinical factors which could influence the
      results of overlapping sphincteroplasty. MATERIAL AND METHODS: Between 2003-2009
      the group of 78 incontinent patients (59 women, mean age of 61+/-13 years), was
      operated on with anterior overlapping anal sphincteroplasty. Only patients with
      severe incontinence (>16 pts in Wexner scale) were included. Before surgery and
      in follow-up period anorectal ultrasound, manometry and incontinence assessment
      were performed and in follow-up period patients additionally fulfilled survey.
      The study was prospective. Follow up period was more than 36 months. RESULTS: In
      survey the excellent results related to 52 patients (66.7%), good in 15 (19.2%)
      and poor in 11 (14.1%). The squeeze pressure improved more significantly in men
      33+/-11 cm H2O vs. 22+/-14 cm H2O; p=0.039. In patients <50 year squeeze pressure
      was significantly larger 32+/-10 cm H2O vs. 25+/-12 cm H2O; p=0.045. If the width
      of a defect within sphincter was less than 60 degrees  the improvement in squeeze
      pressure was higher 33+/-9 cm H2O vs. 22+/-15 cm H2O; p=0.031. In Wexner scale
      male patients better responded to surgery than females 6.94+/-1.8 vs. 5.12+/-2.2,
      p=0.048; as well as patients with smaller scar <60 degrees  6.51+/-1.4 vs. 4.28+/
      2.3; p=0.042. CONCLUSIONS: To succeed in sphincteroplasty the proper
      qualification to the procedure should be crucial. Clinical assessment prior to
      surgery with the use of all available non-surgical methods in patients suffer
      from severe symptoms can help to select optimal group who will benefit from
      surgery. Male patients may have to obtain better outcome and patients with
      smaller sphincter defect could likely have also better results from surgery.

PMID- 24578453
TI  - 18-year old patient with extrahepatic biliary duct carcinoid--case report.
AB  - Most patients with obstructive jaundice caused by an etiology other than
      choledocholithiasis are at risk of adenocarcinoma development. Other types of
      tumors are less common, although more benign. The presented study described
      management in case of liver hilar tumors with special regards to common hepatic
      duct carcinoids.

PMID- 24578454
TI  - Acute compartment syndrome after open forearm fracture--scale of the problem and
      case report.
AB  - Acute compartment syndrome is caused due to a sudden increase in the tissue
      pressure in a given fascial compartment. Missed and undiagnosed or not treated in
      time can lead to irreversible damage to limb muscles and nerves due to ischemia
      mechanism. This paper presents a case of a patient with an open forearm fracture
      treated conservatively in plaster.

PMID- 24578455
TI  - Anastomotic aneurysms after arterial reconstructive operations--literature
      review.

PMID- 24578456
TI  - Menstruation--still a contraindication to elective surgery?

PMID- 24578457
TI  - Laboratory automation: how will you select the boarding assays?

PMID- 24578458
TI  - Long-term statin use and dementia risk in Taiwan.
AB  - BACKGROUND: The effect of statin use on dementia risk remains unclear. This study
      aims to examine the association between long-term statin use and dementia risk.
      METHODS: A nest case-control study within a nationwide representative population
      based cohort. Individuals aged 50 years and older participating in Taiwan's
      National Health Insurance program between 1998 and 2009 were enrolled. A total of
      9257 patients with at least 3 outpatient or 1 inpatient claims records for
      dementia were identified. Comparison patients were selected at a 1:2 ratio from
      age- and sex-matched participants without dementia. The cumulative period and
      average daily dosages of statins, fibrates, and other lipid-lowering agents were
      measured. RESULTS: The authors found a duration-response relationship, as
      dementia risk decreased by 9% per year of treatment of statins (adjusted odds
      ratio = 0.91; 95% confidence interval, 0.85-0.97). Use of high average dose
      statins for more than 1 year was associated with a lower risk of dementia than
      use of low average dose. However, there was no significant difference in dementia
      risks between lipophilic and hydrophilic statins. Fibrates or other lipid
      lowering agents had no significant association with dementia risk. CONCLUSION:
      Our results suggest that long-term use of statin is associated with a reduced
      dementia risk.

PMID- 24578459
TI  - Development and Validation of the Identification and Intervention for Dementia in
      Elderly Africans (IDEA) Study Dementia Screening Instrument.
AB  - AIM: The aim of this project was to develop a dementia screening instrument for
      use in the hospital or community in populations with low levels of formal
      education. METHODS: A screening instrument was developed from retrospective data
      collected in a rural area of Tanzania in 2010. The community screening instrument
      for dementia was administered to over 95% of the population aged 70 years and
      older of 6 villages (n = 1198) in Hai district, Tanzania. Factor analysis,
      regression modeling, and Mokken scale analysis (MSA) were used to develop
      screening instruments from these data, which were then tested and refined during
      prospective fieldwork. RESULTS: A 5-item screening instrument with an area under
      the receiver-operating characteristic (AUROC) curve of 0.871, sensitivity of
      91.7%, and specificity of 61.7% was developed using a combination of factor
      analysis and logistic regression modeling and had a higher AUROC (0.786) than a 7
      item screening instrument developed using MSA. During prospective testing and
      refinement (n = 60), the 5-item instrument performed well (AUROC 0.867) and took
      an average of less than 10 minutes to administer. Its performance was improved by
      including a matchstick design item added to measure praxis, AUROC 0.888.
      CONCLUSIONS: The 6-item brief dementia screening instrument has acceptable
      properties and will be further tested and validated during future fieldwork.
      Although developed for use in sub-Saharan Africa, it may be of use in other world
      regions where the use of other cognitive screening instruments may result in bias
      due to low levels of formal education.

PMID- 24578460
TI  - The Lawton Instrumental Activities Daily Living/Activities Daily Living Scales: A
      Sensitive Test to Alzheimer Disease in Community-Dwelling Elderly People?
AB  - OBJECTIVE: To examine the diagnostic ability of the Lawton Instrumental
      Activities Daily Living (IADLs) scale and the Activities Daily Living (ADLs)
      scale as a sensitive tool to Alzheimer's disease (AD) in community-dwelling
      elderly people. DESIGN: In an old age memory outpatient center, among patients
      with a clinical diagnosis of AD dementia or no dementia supported by at least 6
      months of follow-up, we looked back at the baseline Lawton IADL scale (short
      version IADL-4 item), ADL scale, Mini-Mental State Examination (MMSE), and
      Montreal Cognitive Assessment (MOCA) values. RESULTS: There were 109 patients
      with AD and 53 nondemented individuals (81.4 +/- 4.6 years). The sensitivity of
      ADL scale or IADL-4 item or the MMSE was low (52%-57%). The most efficient AD
      classification used both the IADLs-4 item and the MOCA with a threshold score of
      20. Besides age and memory scores, the main correlates of IADLs scale or ADLs
      scale were executive, neuropsychiatric, vascular, and extrapyramidal scores.
      CONCLUSION: Our results suggest that the Lawton IADLs-4 item scale and ADLs scale
      lack sensitivity to AD dementia in elderly people and support a better
      sensitivity of MOCA rather than MMSE and IADLs-4 item/ADLs at the expense of
      specificity.

PMID- 24578461
TI  - Adverse Childhood and Recent Negative Life Events: Contrasting Associations With
      Cognitive Decline in Older Persons.
AB  - OBJECTIVE: To examine whether persons who experienced adverse childhood events or
      recent negative life events have a worse cognitive performance and faster
      cognitive decline and the role of depression and apolipoprotein E-?4 in this
      relationship. METHODS: The community-based sample consisted of 10-year follow-up
      data of 1312 persons participating in the Longitudinal Aging Study Amsterdam (age
      range 65-85 years). RESULTS: Persons who experienced adverse childhood events
      showed a faster 10-year decline in processing speed but only when depressive
      symptoms were experienced. Persons with more recent negative life events showed
      slower processing speed at baseline but no faster decline. CONCLUSIONS: Childhood
      adversity may cause biological or psychological vulnerability, which is
      associated with both depressive symptoms and cognitive decline in later life. The
      accumulation of recent negative life events did not affect cognitive functioning
      over a longer time period.

PMID- 24578462
TI  - Screening for Mild Cognitive Impairment Using the Dementia Rating Scale-2.
AB  - This study examined the sensitivity and specificity of the Dementia Rating Scale
      2 (DRS-2) to distinguish individuals with mild cognitive impairment (MCI) from
      both patients with Alzheimer's disease (AD) and healthy controls (HCs). A total
      of 50 HCs, 98 patients with MCI, and 49 patients with AD completed a neurological
      examination and battery of neuropsychological tests that included the DRS-2.
      Across almost all subscales of the DRS-2, patients with AD scored significantly
      worse than patients with MCI who in turn performed more poorly than the HCs. The
      only exception was the construction subscale where no significant difference was
      found between patients with MCI and the HCs. At a cutoff of 136, the sensitivity
      was 71% and specificity was 86% for distinguishing between patients with MCI and
      the HCs. Sensitivity was 82% and specificity was 78% for distinguishing between
      patients with MCI and patients with AD (cutoff score <124). For distinguishing
      between patients (with MCI and AD) and the HCs, sensitivity was 81% and
      specificity was 86% at a cutoff of 136. Our findings suggest the DRS-2 is a
      brief, easily administered cognitive test that appears to be useful in assisting
      with the detection of MCI. 

PMID- 24578463
TI  - Validation of Montreal Cognitive Assessment and Discriminant Power of Montreal
      Cognitive Assessment Subtests in Patients With Mild Cognitive Impairment and
      Alzheimer Dementia in Turkish Population.
AB  - Montreal Cognitive Assessment (MoCA) is a new cognitive tool developed for
      screening mild cognitive impairment (MCI). The authors examined validity of MoCA
      and discriminating power of subtests in a Turkish population comprising of 474
      participants (246 healthy controls, 114 subjects with MCI and 114 subjects with
      dementia). The ANCOVAs showed that age and education had a main effect on MoCA
      scores. Cut scores were computed according to different education levels. The
      overall cut-off values for MCI and dementia were found to be lower compared to
      western studies. MoCA was found to have good internal consistency. The subtests
      most useful in discriminating MCI from healthy controls were recall, visuospatial
      and language, while in discriminating dementia from MCI were visuospatial,
      orientation and attention subtests. The results demonstrated that MoCA is a valid
      and reliable instrument in screening MCI, and compared with the MMSE, MoCA was
      proved to have superior sensitivity and specificity in detecting MCI. 

PMID- 24578464
TI  - The dangers of injecting blind: Abductor pollicis longus tendon rupture in de
      Quervain's disease.

PMID- 24578466
TI  - Long-Term Mortality After Pneumonia in Cardiac Surgery Patients: A Propensity
      Matched Analysis.
AB  - BACKGROUND: The role that intensive care unit (ICU)-acquired pneumonia plays in
      the long-term outcomes of cardiac surgery patients is not well known. This study
      examined the association of pneumonia with in-hospital mortality and long-term
      mortality after adult cardiac surgery. METHODS: A total of 2750 patients admitted
      to our ICU after cardiac surgery from January 2003 to December 2009 are the basis
      for this observational study. Patients who developed ICU-acquired pneumonia were
      matched with patients without it in a 1:2 ratio. The matching criteria were age,
      urgent or scheduled surgery, surgical procedure, and the propensity score for
      pneumonia. Multiple regression analysis was used to find predictors of hospital
      mortality. The relationship between pneumonia and long-term survival was analyzed
      with Kaplan-Meier survival estimates and a risk-adjusted Cox proportional
      regression model for patients discharged alive from hospital. RESULTS: Pneumonia
      was diagnosed in 32 (1.2%) patients and there were 19 cases per 1000 days of
      mechanical ventilation. Patients with pneumonia had a significantly higher
      hospital mortality rate (28% vs 6.2%, P = .003) and a higher mortality at the end
      of follow-up (53% vs 19%, P < .0001) than those without it. Regression analysis
      showed that pneumonia was a strong predictor of hospital mortality. Five-year
      survival was as follows: pneumonia, 62%; control, 81%; and cohort patients, 91%.
      The Cox model showed that, after adjusting for confounding factors, patients with
      pneumonia (hazard ratio = 3.96, 95% confidence interval [CI]: 1.41-11.14) had
      poorer long-term survival. CONCLUSION: Pneumonia remains a serious complication
      in patients operated for cardiac surgery and is associated with increased
      hospital mortality and reduced long-term survival.

PMID- 24578465
TI  - Coefficient of Variation of Coarsely Sampled Heart Rate is Associated With Early
      Vasopressor Independence in Severe Sepsis and Septic Shock.
AB  - PURPOSE: To determine whether variability of coarsely sampled heart rate and
      blood pressure early in the course of severe sepsis and septic shock predicts
      successful resuscitation, defined as vasopressor independence at 24 hours after
      admission. METHODS: In an observational study of patients admitted with severe
      sepsis or septic shock from 2009 to 2011 to either of 2 intensive care units
      (ICUs) at a tertiary-care hospital, in whom blood pressure was measured via an
      arterial catheter, we sampled heart rate and blood pressure every 30 seconds over
      the first 6 hours of ICU admission and calculated the coefficient of variability
      of those measurements. Primary outcome was vasopressor independence at 24 hours;
      and secondary outcome was 28-day mortality. RESULTS: We studied 165 patients, of
      which 97 (59%) achieved vasopressor independence at 24 hours. Overall, 28-day
      mortality was 15%. Significant predictors of vasopressor independence at 24 hours
      included the coefficient of variation of heart rate, age, Acute Physiology and
      Chronic Health Evaluation II, the number of increases in vasopressor dose, mean
      vasopressin dose, mean blood pressure, and time-pressure integral of mean blood
      pressure less than 60 mm Hg. Lower sampling frequencies (up to once every 5
      minutes) did not affect the findings. CONCLUSIONS: Increased variability of
      coarsely sampled heart rate was associated with vasopressor independence at 24
      hours after controlling for possible confounders. Sampling frequencies of once in
      5 minutes may be similar to once in 30 seconds.

PMID- 24578468
TI  - Repeat protocol renal biopsy in ANCA-associated renal vasculitis.
AB  - BACKGROUND: Histopathological lesions in renal biopsy (RB) at presentation of
      ANCA-associated vasculitis (AAV) have been described in depth but repeat
      protocolized renal biopsies are seldomly performed in AAV. In this study, we
      present a group of AAV patients with repeat protocolized biopsies, and we
      evaluate their clinical significance. METHODS: A total of 17 consecutive patients
      diagnosed between 1991 and 1995 with AAV and renal involvement confirmed by
      biopsy at presentation in a single center underwent a protocol planned rebiopsy
      in remission after a median of 13 months (range 11-28) from diagnosis. Biopsies
      were assessed by two independent pathologists, blinded to patient data. Clinical
      data were collected retrospectively. RESULTS: Patients were followed-up for a
      median of 189 months from diagnosis. Renal relapse was observed in eight patients
      (47.1%), seven patients died, three patients reached end-stage renal failure.
      There was a significant decrease in the percentage of acute lesions (cellular
      crescents, fibrinoid necrosis, P < 0.001) and a significant increase in chronic
      lesions (glomerulosclerosis, interstitial fibrosis, P <= 0.01) in the repeat RB
      compared with the first RB. This resulted in a class change over the biopsies
      within most patients. The percentage of normal glomeruli in the first biopsy
      positively correlated with estimated GFR at the end of follow-up (rs = 0.509, P =
      0.05). CONCLUSIONS: This is the first study on protocolized repeat biopsies in
      AAV, giving insight into disease activity under immunosuppressive treatment.
      Apparently, many AAV patients have grumbling disease with ongoing activity,
      eventually leading to an increased amount of chronic lesions.

PMID- 24578469
TI  - Soluble Flt-1 release response to heparin use: implications for dialysis
      patients?

PMID- 24578470
TI  - Randomized controlled study of icodextrin on the treatment of peritoneal dialysis
      patients during acute peritonitis.
AB  - BACKGROUND: The clinical benefits of using icodextrin during acute peritonitis in
      peritoneal dialysis are uncertain. On the premise that high glucose concentration
      might jeopardize the peritoneal defense during peritonitis, icodextrin
      administration during acute peritonitis could have the potential to improve the
      peritonitis outcome whilst improving ultrafiltration. METHODS: We conducted a
      single-center, open-label, randomized controlled trial in which 53 adult
      continuous ambulatory peritoneal dialysis patients underwent randomization to
      receive either icodextrin or original glucose-based dialysis solution. The
      primary outcome measure was the peritoneal dialyzate white cell count on Day 3.
      Secondary outcome measures comprised the need of additional hypertonic exchanges,
      fluid control as denoted by changes in body weight, and the clinical outcome of
      peritonitis including 30-day and 120-day all-cause mortality. RESULTS: Between
      icodextrin and control treatment groups, there were no statistically significant
      differences in the peritoneal dialyzate white cell count on day (1829 versus
      987/mm(3), P = 0.13). There was neither improvement in primary cure rate (31.8
      versus 32.3%, P = 1.00), nor was there any change in 120-day mortality after
      icodextrin use (13.6 versus 12.9%, P = 1.00). However, requirement of hypertonic
      dialysis exchange was much more frequent in the control group than in those
      randomized to icodextrin (35.5 versus 0%, P = 0.001). Body weight did not change
      significantly in the icodextrin group, but body weight in the control group
      increased from 63.3 +/- 14.5 kg at baseline to 64.2 +/- 14.2 kg at Day 5 (P =
      0.0002) and 65.2 +/- 14.1 kg at Day 10 (P < 0.0001). CONCLUSIONS: As compared
      with glucose-based peritoneal dialysis solution, use of icodextrin achieved
      better ultrafiltration and fluid control during acute peritonitis complicating
      continuous ambulatory peritoneal dialysis, although we found no evidence of a
      worthwhile clinical benefit on peritonitis resolution. (ClinicalTrial.gov number,
      NCT0104446 [ClinicalTrial.gov].).

PMID- 24578471
TI  - A randomized comparison of 1-h sodium bicarbonate hydration versus standard peri
      procedural saline hydration in patients with chronic kidney disease undergoing
      intravenous contrast-enhanced computerized tomography.
AB  - BACKGROUND: Guidelines recommend saline hydration for prophylaxis of contrast
      induced acute kidney injury (CI-AKI) in patients with chronic kidney disease
      (CKD) undergoing intravenous contrast media-enhanced CT (CE-CT). The safety and
      efficacy of a brief hydration protocol using sodium bicarbonate in this
      population is unknown. We analysed whether 1-h sodium bicarbonate hydration prior
      to CE-CT is non-inferior to saline hydration prior to and after CE-CT in CKD
      patients. METHODS: We performed an open-label multicentre randomized trial.
      Patients were randomized to 250 mL of 1.4% sodium bicarbonate hydration prior to
      CE-CT or 1000 mL of 0.9% saline hydration prior to and, once again, after CE-CT.
      Primary outcome was the relative increase in serum creatinine 48-96 h post-CE-CT.
      Secondary outcomes were incidence of CI-AKI [serum creatinine increase >25%/>44
      umol/L (0.5 mg/dL)], recovery of renal function, the need for dialysis and 2
      month hospital costs. RESULTS: Five hundred and seventy adult CKD patients
      undergoing CE-CT were randomized between 2010 and 2012, of whom 548 were included
      in the intention-to-treat population. Mean relative serum creatinine increase was
      1.2% for sodium bicarbonate and 1.5% for saline (mean difference -0.3%; 95%
      confidence interval -2.7 to 2.1, P-value for non-inferiority <0.0001). CI-AKI
      occurred in 22 patients (4.1%); 8 (3.0%) randomized to sodium bicarbonate versus
      14 (5.1%) to saline (P = 0.23). Renal function recovered in 75 and 69% of CI-AKI
      patients, respectively (P = 0.81). No patients developed a need for dialysis.
      Mean hydration costs per patient were ?224 for the sodium bicarbonate and ?683
      for the saline regime (P < 0.001). Other healthcare costs were similar.
      CONCLUSIONS: Short hydration with sodium bicarbonate prior to CE-CT was non
      inferior to peri-procedural saline hydration with respect to renal safety and may
      result in healthcare savings. [Netherlands Trial Register
      (http://www.trialregister.nl/trialreg/index.asp), Nr 2149, date of registration
      23 December 2009.].

PMID- 24578472
TI  - Combined blockade of angiotensin II type 1 receptor and activation of peroxisome
      proliferator-activated receptor-gamma by telmisartan effectively inhibits
      vascularization and growth of murine endometriosis-like lesions.
AB  - STUDY QUESTION: Is telmisartan effective in the treatment of endometriosis?
      SUMMARY ANSWER: Combined blockade of angiotensin II type 1 receptor (AT1R) and
      activation of peroxisome proliferator-activated receptor (PPAR)-gamma by
      telmisartan inhibits vascularization and growth of murine endometriosis-like
      lesions. WHAT IS KNOWN ALREADY: AT1R and PPAR-gamma are involved in the
      regulation of inflammation, proliferation and angiogenesis. These processes are
      also crucial for the pathogenesis of endometriosis and both receptors are
      expressed in endometrial tissue. Telmisartan is a partial agonist of PPAR-gamma,
      which additionally blocks AT1R. STUDY DESIGN, SIZE, DURATION: This was a
      randomized study in the mouse dorsal skinfold chamber and peritoneal model of
      endometriosis. Endometriosis-like lesions were induced in dorsal skinfold
      chambers of 21 female C57BL/6 mice, and in the peritoneal cavity of 15 additional
      animals, which were daily treated with an i.p. injection of pioglitazone (10
      mg/kg, n = 12), telmisartan (10 mg/kg, n = 12) or vehicle (5% dimethyl sulfoxide
      (DMSO), n = 12) throughout an observation period of 14 and 28 days, respectively.
      PARTICIPANTS/MATERIALS, SETTING, METHODS: The anti-angiogenic actions of
      pioglitazone, a full PPAR-gamma agonist, and telmisartan were firstly assessed in
      vitro by an aortic ring assay. Endometriosis-like lesions were induced in the
      dorsal skinfold chamber or peritoneal cavity and the effects of telmisartan and
      pioglitazone on their vascularization, immune cell content and growth were
      studied by intravital fluorescence microscopy, high-resolution ultrasound imaging
      as well as histological, immunohistochemical and immunofluorescent analyses.
      Additional quantitative real-time polymerase chain reaction (qRT-PCR) arrays
      served for gene expression profiling of the lesions. To limit the role of chance,
      the experiments were conducted under standardized laboratory conditions with
      appropriate vehicle-treated controls. Statistical significance was accepted for a
      value of P < 0.05. MAIN RESULTS AND THE ROLE OF CHANCE: Telmisartan inhibited
      vascular sprout formation of aortic rings more effectively than pioglitazone.
      Accordingly, endometriosis-like lesions in dorsal skinfold chambers of
      telmisartan-treated animals exhibited a markedly lower functional microvessel
      density and blood perfusion. High-resolution ultrasound analyses of peritoneal
      endometriosis-like lesions revealed that the compound inhibited the stromal
      tissue growth, resulting in a significantly reduced final lesion volume. In
      contrast, the development of cysts did not differ between the groups. Moreover,
      telmisartan induced an up-regulation of PPAR-gamma and a down-regulation of AT1R
      proteins in endometriosis-like lesions, which was associated with a decreased
      density of CD31-positive microvessels, a reduced immune cell content and a lower
      number of Ki67-positive proliferating cells. qRT-PCR arrays further demonstrated
      an inhibitory action of telmisartan on the expression of several angiogenic and
      inflammatory genes. LIMITATIONS, REASONS FOR CAUTION: Endometriosis-like lesions
      were induced by syngeneic tissue transplantation into recipient mice without the
      use of pathological endometriotic tissue of human nature. Therefore, the results
      obtained in this study may not fully relate to human patients with endometriosis.
      WIDER IMPLICATIONS OF THE FINDINGS: This study demonstrates that telmisartan
      inhibits vascularization, immune cell content and growth of endometriosis-like
      lesions. Accordingly, the combined blockade of AT1R and activation of PPAR-gamma
      represents a promising new concept in the development of novel compounds for the
      treatment of endometriosis. STUDY FUNDING/COMPETING INTEREST(S): There was no
      specific funding of this study. The authors have no conflicts of interest to
      declare.

PMID- 24578473
TI  - A single-centre evaluation of two new anti-Mullerian hormone assays and
      comparison with the current clinical standard assay.
AB  - STUDY QUESTION: Are the new Ansh Labs Ultra-Sensitive anti-Mullerian hormone
      (AMH) and picoAMH ELISA assays suitable for clinical use and is the Ultra
      Sensitive assay comparable to the Beckman Coulter AMH Gen II assay? SUMMARY
      ANSWER: The Ultra-Sensitive assay appears to have different calibration to the
      Gen II assay, but has performance characteristics generally suitable for clinical
      use. WHAT IS KNOWN ALREADY: The Gen II assay is the most commonly used AMH assay
      in routine biochemistry at present, but persistent calibration/interference
      problems have been reported. STUDY DESIGN, SIZE, DURATION: Serum from patients
      referred for AMH measurement was assayed (in duplicate) using the Gen II assay in
      Glasgow Royal Infirmary between January and February 2013. We randomly selected
      193 stored serum samples to re-run (in duplicate) using the Ultra-Sensitive AMH
      Ansh Labs assay, blinded to the original result. Samples that returned low
      results were run on the picoAMH Ansh Labs assay. Performance characteristics and
      linearity of the new assays were also assessed. PARTICIPANTS/MATERIALS, SETTING,
      METHODS: All serum samples from patients referred for AMH at Glasgow Royal
      Infirmary between January and February 2013 were eligible for inclusion.
      Investigators were blinded to any identifiable information regarding the
      patients, including sex, age and reason for AMH measurement. MAIN RESULTS AND THE
      ROLE OF CHANCE: Intra-assay and inter-assay coefficients of variation of the
      Ultra-Sensitive and picoAMH assays were <=6.0 and <=10.7%, respectively, over a
      range of concentrations. The assays had mean linearity of 98 and 97% over the
      dilution range of 1:2-1:16 and 1:2-1:8, respectively. The limit of detection of
      the ultrasensitive assay was calculated to be 0.34 pmol/l. For 166 samples which
      provided a quantitative result on the Gen II and Ultra-Sensitive Ansh Labs
      assays, the median (interquartile range) was 12.2 (3.4-29.3) pmol/l and 20.0 (6.6
      36.8) pmol/l, respectively (P<0.0001). The Passing-Bablok regression equation (in
      pmol/l) was y (Ultra-Sensitive) = 1.7 + 1.4 * Gen II. More samples were below the
      clinical cut-off of 5.4 pmol/l using the Gen II assay (a difference between
      paired proportions of 15.0%, P < 0.001). Fifteen of the 22 undetectable samples
      yielded a measurable concentration result on the picoAMH assay. LIMITATIONS,
      REASONS FOR CAUTION: The present study is a pragmatic assessment of the new assay
      under ideal conditions. Lot-to-lot variation could not be assessed. Demographics
      and outcomes of patients referred for AMH measurement were not known. WIDER
      IMPLICATIONS OF THE FINDINGS: The Ansh Labs Ultra-Sensitive assay performance
      characteristics are similar to the Gen II assay and may be suitable for clinical
      and epidemiological use. Enhanced sensitivity of the Ansh Labs picoAMH assay
      enables measurement of low AMH concentrations. These results re-emphasize the
      need for an AMH international standard. STUDY FUNDING/COMPETING INTEREST(S): Ansh
      Labs provided kits for this study free of charge. The manufacturer played no part
      in conducting assays or data analysis. S.M.N. has received speaker's fees and
      participated in advisory boards for Beckman Coulter, Merck Serono, MSD and
      Ferring regarding AMH. P.W. is supported by British Heart Foundation fellowship
      FS/12/62/29889. We declare no other financial relationship or competing
      interests.

PMID- 24578474
TI  - Parental age at delivery and a man's semen quality.
AB  - STUDY QUESTION: Is parental age at delivery associated with a man's semen
      quality? SUMMARY ANSWER: In this large register-based study both mother's and
      father's age are found to have minimal effects on semen quality in men. WHAT IS
      KNOWN ALREADY: Both maternal and paternal age have been associated with a range
      of adverse health effects in the offspring. Given the varied health effects of
      parental age upon offspring, and the sensitivity of genital development to
      external factors, it is plausible that the age of a man's mother and father at
      conception may impact his reproductive health. To our knowledge this is the first
      examination of the effects of parental age on semen quality. STUDY DESIGN, SIZE,
      DURATION: A retrospective cohort study of 10 965 men with semen data and parental
      data. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study was based on Danish men
      referred to the Copenhagen Sperm Analysis Laboratory due to infertility in their
      partnership. Men born from 1960 and delivering a semen sample until year 2000
      were included. The men were linked to the Danish Civil Registration System to
      obtain information on parent's age at delivery. Logistic regression analyses were
      used to calculate odds ratios and 95% confidence intervals for impaired semen
      quality. Linear regression analyses were used to examine a relationship between
      semen parameters and paternal age. MAIN RESULTS AND THE ROLE OF CHANCE: There
      were no convincing effect of either mother's or father's age on a man's semen
      quality. As no trends were noted, the few statistically significant results are
      likely attributable to chance. LIMITATIONS, REASONS FOR CAUTION: Information
      regarding individual subject characteristics which may impact sperm production
      (i.e. smoking, BMI) were not available. While our sample size was large, we
      cannot exclude the possibility that a trend may have been identified with a still
      larger sample. In addition, the Danish Civil Registration System is merely
      administrative and hence does not discriminate between biological and adopted
      children. However, the low rate of adoption (~2%) suggests that misclassification
      would have a minimal impact. The men were all referred to the laboratory for
      infertility problems in their partnership and, therefore, do not represent the
      general population. We, however, compared semen quality among men within the
      cohort, and it is therefore less important whether they, in fact, represent the
      general population. WIDER IMPLICATIONS OF THE FINDINGS: The current study found
      no link between parental age and a son's semen quality, suggesting other factors
      may explain recent impairments in men's reproductive health. STUDY
      FUNDING/COMPETING INTEREST(S): This work was supported by the Hans and Nora
      Buchard's Fund and the Kirsten and Freddy Johansen's Fund. No competing
      interests. TRIAL REGISTRATION NUMBER: Not relevant.

PMID- 24578475
TI  - Correlation between standard blastocyst morphology, euploidy and implantation: an
      observational study in two centers involving 956 screened blastocysts.
AB  - STUDY QUESTION: Does conventional blastocyst morphological evaluation correlate
      with euploidy (as assessed by comprehensive chromosome screening (CCS) of
      trophectoderm (TE) biopsies) and implantation potential? SUMMARY ANSWER: A
      moderate relation between blastocyst morphology and CCS data was observed but the
      ability to implant seems to be mainly determined by the chromosomal complement of
      preimplantation embryos rather than developmental and morphological parameters
      conventionally used for blastocyst evaluation. WHAT IS KNOWN ALREADY: Combined
      with improving methods for cryopreservation and blastocyst culture, TE biopsy and
      CCS is considered to be a promising approach to select euploid embryos for
      transfer. Understanding the role of morphology in blastocyst stage
      preimplantation genetic screening (PGS) cycles may help in further optimizing the
      cycle management and clinical outcomes. STUDY DESIGN, SIZE, DURATION: This is a
      multicenter retrospective observational study performed between January 2009 and
      August 2013. The study includes the data analysis of 956 blastocysts with
      conclusive CCS results obtained from 213 patients following 223 PGS cycles.
      Single frozen embryo transfer (FET) cycles of 215 euploid blastocysts were
      performed where it was possible to track the implantation outcome of each embryo
      transferred. PARTICIPANTS/MATERIALS, SETTING, METHODS: PGS was offered to
      infertile patients of advanced maternal age (>35 years) and/or with a history of
      unsuccessful IVF treatments (more than two failed IVF cycles) and/or previous
      spontaneous abortion (more than two spontaneous miscarriages). Prior to TE biopsy
      for CCS, blastocyst morphology was assessed and categorized in four groups
      (excellent, good, average and poor quality). The developmental rate of each
      embryo reaching the expanded blastocyst stage was defined according to the day of
      biopsy post-fertilization. Day 5 and Day 6 biopsied blastocysts were defined as
      faster and slower growing embryos, respectively. A novel blastocyst biopsy
      method, not requiring the opening of the zona pellucida at the cleavage stage of
      embryo development, was used. Linear regression models were used to test the
      relationship between blastocyst morphology and developmental rate CCS data and
      FET cycle outcomes of euploid blastocysts. MAIN RESULTS AND THE ROLE OF CHANCE:
      Among the embryological variables assessed (morphology and developmental rate),
      only blastocyst morphology was predictive of the CCS data. The euploidy rate was
      56.4, 39.1, 42.8 and 25.5% in the excellent, good, average and poor blastocyst
      morphology groups, respectively. A diagnosis of complex aneuploidy was also
      associated with blastocyst morphology (P < 0.01) with 6.8, 15.2, 17.4 and 27.5%
      of excellent, good, average and poor quality embryos, respectively, showing
      multiple chromosome errors. Faster and slower growing embryos showed a similar
      aneuploidy rate. Regression logistic analysis showed that none of the parameters
      used for conventional blastocyst evaluation (morphology and developmental rate)
      was predictive of the implantation potential of euploid embryos. The implantation
      potential of euploid embryos was the same, despite different morphologies and
      developmental rates. LIMITATIONS, REASONS FOR CAUTION: The study is limited by
      its retrospective nature. A higher sample size or a prospective randomized design
      could be used in future studies to corroborate the current findings. WIDER
      IMPLICATIONS OF THE FINDINGS: This study provides knowledge for a better
      laboratory and clinical management of blastocyst stage PGS cycles suggesting that
      the commonly used parameters of blastocyst evaluation are not good enough
      indicators to improve the selection among euploid embryos. Accordingly, all poor
      morphology and slower growing expanded blastocysts should be biopsied and
      similarly considered for FET cycles. This knowledge will be of critical
      importance to achieve similar cumulative live birth rates in PGS programs
      compared with conventional IVF, avoiding the potential for exclusion of low
      quality but viable embryos from the biopsy and transfer procedures. Future
      research to identify non-invasive biomarkers of reproductive potential may
      further enhance selection among euploid blastocysts. STUDY FUNDING/COMPETING
      INTEREST(S): No funding was obtained for the study. All authors have no conflicts
      to declare. TRIAL REGISTRATION NUMBER: None.

PMID- 24578476
TI  - Hysterosalpingosonography for diagnosing tubal occlusion in subfertile women: a
      systematic review with meta-analysis.
AB  - STUDY QUESTION: Is hysterosalpingosonography (sono-HSG) an accurate test for
      diagnosing tubal occlusion in subfertile women and how does it perform compared
      with hysterosalpingography (HSG)? SUMMARY ANSWER: sono-HSG is an accurate test
      for diagnosing tubal occlusion and performs similarly to HSG. WHAT IS KNOWN
      ALREADY: sono-HSG and HSG are both short, well-tolerated outpatient procedures.
      However, sono-HSG has the advantage over HSG of obviating ionizing radiation and
      the risk of iodine allergy, being associated with a greater sensitivity and
      specificity in detecting anomalies of the uterine cavity and permitting
      concomitant visualization of the ovaries and myometrium. STUDY DESIGN, SIZE,
      DURATION: A systematic review and meta-analysis of studies published in any
      language before 14 November 2012 were performed. All studies assessing the
      accuracy of sono-HSG for diagnosing tubal occlusion in a subfertile female
      population were considered. PARTICIPANTS/MATERIALS, SETTING, METHODS: We searched
      Medline, Embase, Cochrane Library, Web of Science and Biosis as well as related
      articles, citations and reference lists. Diagnostic studies were eligible if they
      compared sono-HSG (+/-HSG) to laparoscopy with chromotubation in women suffering
      from subfertility. Two authors independently screened for eligibility, extracted
      data and assessed the quality of included studies. Risk of bias and applicability
      concerns were investigated according to the Quality Assessment of Diagnostic
      Accuracy Study (QUADAS-2). Bivariate random-effects models were used to estimate
      pooled sensitivity and specificity with their 95% confidence intervals (95% CIs),
      to generate summary receiver operating characteristic curves and to evaluate
      sources of heterogeneity. MAIN RESULTS AND THE ROLE OF CHANCE: Of the 4221
      citations identified, 30 studies were eligible. Of the latter, 28 reported
      results per individual tube and were included in the meta-analysis, representing
      a total of 1551 women and 2740 tubes. In nine studies, all participants underwent
      HSG in addition to sono-HSG and laparoscopy, allowing direct comparison of the
      accuracy of sono-HSG and HSG. Pooled estimates of sensitivity and specificity of
      sono-HSG were 0.92 (95% CI: 0.82-0.96) and 0.95 (95% CI: 0.90-0.97),
      respectively. In nine studies (582 women, 1055 tubes), sono-HSG and HSG were both
      compared with laparoscopy, giving pooled estimates of sensitivity and specificity
      of 0.95 (95% CI: 0.78-0.99) and 0.93 (95% CI: 0.89-0.96) for sono-HSG, and 0.94
      (95% CI: 0.74-0.99) and 0.92 (95% CI: 0.87-0.95) for HSG, respectively. Doppler
      sonography was associated with significantly greater sensitivity and specificity
      of sono-HSG compared with its non-use (0.93 and 0.95 versus 0.86 and 0.89,
      respectively, P = 0.0497). Sensitivity analysis regarding methodological quality
      of studies was consistent with these findings. We also found no benefit of the
      commercially available contrast media over saline solution in regard to the
      diagnostic accuracy of sono-HSG. LIMITATIONS, REASONS FOR CAUTION: Methodological
      quality varied greatly between studies. However, sensitivity analysis, taking
      methodological quality of studies into account, did not modify the results. This
      systematic review did not allow the distinction between distal and proximal
      occlusion. This could be interesting to take into account in further studies, as
      the performance of the test may differ for each localization. WIDER IMPLICATIONS
      OF THE FINDINGS: Given our findings and the known benefits of sono-HSG over HSG
      in the context of subfertility, sono-HSG should replace HSG in the initial workup
      of subfertile couples. STUDY FUNDING/COMPETING INTEREST(S): This study was funded
      by personal funds. There are no conflicts of interest to declare. TRIAL
      REGISTRATION NUMBER: This review has been registered at PROSPERO: Registration
      number #CRD42013003829.

PMID- 24578477
TI  - Risk of stillbirth and infant deaths after assisted reproductive technology: a
      Nordic study from the CoNARTaS group.
AB  - STUDY QUESTION: Is the risk of stillbirth and perinatal deaths increased after
      assisted reproductive technology (ART) compared with pregnancies established by
      spontaneous conception (SC)? SUMMARY ANSWER: A significantly increased risk of
      stillbirth in ART singletons was only observed before 28 + 0 gestational weeks.
      WHAT IS KNOWN ALREADY: The current literature indicates that children born after
      ART have an increased risk of perinatal death. The knowledge on stillbirth in ART
      pregnancies is limited. STUDY DESIGN, SIZE, DURATION: A population based case
      control study. PARTICIPANTS/MATERIALS, SETTING AND METHODS: A total of 62 485
      singletons and 29 793 twins born after ART in Denmark, Finland, Norway and
      Sweden, from 1982 to 2007, were compared with 362 798 spontaneously conceived
      (SC) singletons and 132 181 twins. MAIN RESULTS AND THE ROLE OF CHANCE: The
      adjusted rate ratio for stillbirth at gestational weeks 22 + 0 to 27 + 6 was 2.08
      [95% confidence interval (CI) 1.55-2.78] for ART versus SC singletons. After 28 +
      0 gestational weeks there was no significant difference in the risk of stillbirth
      between ART and SC singletons. ART twins had a lower risk of stillbirth compared
      with SC twins, but when restricting the analysis to opposite-sex twins and
      excluding all monozygotic twins, there was no significant difference between the
      groups. Singletons conceived by ART had an overall increased risk of early
      neonatal death (adjusted odds ratio 1.54, 95% CI 1.28-1.85) and death within the
      first year after birth (1.45, 1.26-1.68). No difference regarding these two
      parameters was found when further adjusting for the gestational age [(0.97, 0.80
      1.18) and (0.99, 0.85-1.16), respectively]. ART twins had a lower risk of early
      neonatal and infant deaths than SC twins, but no difference was found when
      restricting the analyses to opposite-sex twins. LIMITATIONS, REASON FOR CAUTION:
      We were not able to adjust for potential confounders, such as a prior history of
      stillbirth, induction of labour, body mass index or smoking. WIDER IMPLICATIONS
      OF THE FINDINGS: The risk of stillbirth in ART versus SC singletons was only
      increased for very early gestational ages (before 28 weeks). This might indicate
      that the current clinical management of ART pregnancies is sufficient regarding
      prevention of stillbirth during the third trimester. STUDY FUNDING/COMPETING
      INTEREST(S): No conflict of interest was reported. The European Society for Human
      Reproduction and Embryology (ESHRE), the University of Copenhagen, Denmark, the
      Danish Agency for Science, Technology and Innovation and Sahlgrenska University
      Hospital, Gothenburg, Sweden supported the project. The CoNARTaS group has
      received travel and meeting funding from the Nordic Society of Obstetrics and
      Gynecology (NFOG).

PMID- 24578478
TI  - Serum albumin and HCO3- regulate separate pools of ATP in human spermatozoa.
AB  - STUDY QUESTION: Do the known capacitating agents HCO(3)(-) and serum albumin
      regulate the generation of ATP required for sperm motility and capacitation?
      SUMMARY ANSWER: Serum albumin and HCO(3)(-) seem to regulate two separate pools
      of ATP by different mechanisms in human spermatozoa. WHAT IS KNOWN ALREADY: Sperm
      capacitation is a maturation process that naturally occurs in the female
      reproductive tract preparing the sperm cell for fertilization. It is a highly
      energy-depending process as it involves hyperactive motility and substantial
      levels of protein phosphorylation. STUDY DESIGN, SIZE, DURATION: Human sperm
      cells from four (motility experiments) and three (all other experiments) healthy
      donors were used. Untreated cells were compared with cells treated with HCO(3)(-)
      and serum albumin for up to 4 h. PARTICIPANTS/MATERIALS, SETTING, METHODS:
      Changes in glycolysis and mitochondrial respiration rates upon treatment with
      serum albumin and HCO(3)(-) were analysed by metabolic tracing of (13)C-labelled
      substrates and respirometry studies, respectively. Levels of hyperactive
      spermatozoa and ATP content were measured during 4 h of incubation under
      capacitating conditions. MAIN RESULTS AND THE ROLE OF CHANCE: We found that
      HCO(3)(-) significantly (P < 0.05) increased glycolytic flux by >3-folds via a
      cAMP/PKA sensitive pathway. This was accompanied by an increase in hyperactive
      motility. In contrast, serum albumin significantly increased endogenous ATP
      levels by 50% without stimulating hyperactive motility or glycolysis, indicating
      that this pool of ATP is separately located from the HCO(3)(-)-induced ATP. The
      increase in ATP induced by albumin could be mimicked by treatment with the
      cholesterol acceptors 2-hydroxypropyl- and methyl-beta-cyclodextrin and
      counteracted by co-incubation with cholesterol sulphate to the level of the non
      treated control (P < 0.05), pointing to cholesterol extraction from the sperm
      cell membrane as the main mechanism. However, the concentration of cyclodextrins
      needed to directly detect cholesterol extraction from the sperm cells was not
      compatible with maintenance of sperm viability. The increase in ATP seemed not to
      be dependent on the sperm-specific Ca(2+) channel CatSper. Finally, we
      demonstrated that neither HCO(3)(-) nor serum albumin stimulated mitochondrial
      respiration rates. However, serum albumin increased the respiratory capacity of
      mitochondria by >50%, an effect that was counteracted by HCO(3)(-). LIMITATIONS,
      REASONS FOR CAUTION: Great variation in motility and capacitation is observed
      between sperm cells from different species. Hence, caution should be taken when
      extrapolating the findings in this work on human spermatozoa to sperm from other
      species. WIDER IMPLICATIONS OF THE FINDINGS: It is already established that an
      efficient energy-generation is required to support sperm motility and
      capacitation. However, the mechanisms explaining how ATP production is regulated
      in spermatozoa are not fully understood. Our findings indicate that HCO(3)(-)
      stimulates hyperactive motility by increasing glycolytic flux and ATP production
      in a cAMP/PKA sensitive fashion. On the other hand, serum albumin seems to
      increase ATP concentration at a different location and by a mechanism different
      from glycolysis that involves extraction of cholesterol from the sperm cell
      membrane. These new insights into sperm metabolism may pave the way for both the
      development of new and improved male contraceptives and optimized assisted
      reproduction techniques. STUDY FUNDING: The work was funded by Spermatech AS, The
      University of Oslo and the Research Council of Norway. COMPETING INTEREST(S):
      T.H.H. and K.R.R. are employees at Spermatech. B.S.S is a shareholder in
      Spermatech.

PMID- 24578480
TI  - Left-sided mini-maze procedure via the left atrial appendage.
AB  - This study presents a novel way to perform the mini-maze procedure through the
      left atrial appendage. By this way, the usual additional incision of the intra
      atrial groove is avoided, especially in patients receiving coronary artery bypass
      grafting (CABG) or aortic valve replacement without mitral valve disease. We
      retrospectively analysed 23 consecutive patients who received this novel mini
      maze procedure between 2009 and 2011. In recognition of a learning curve, we
      divided the patients into two groups (Group 1: Patients 1-11 versus Group 2:
      Patients 12-23), according to the date of operation. In Group 2, 7 patients
      (58.33%) were completely free of atrial fibrillation at the time of the follow
      up. In Group 1, only 2 (18.18%) patients were successfully treated resulting in a
      stable sinus rhythm at the time of the follow-up. The mini-maze procedure
      performed through the left atrial appendage is a safe and feasible technique;
      however, it seems to be less effective than the Cox-maze III procedure and is
      associated with a learning curve.

PMID- 24578482
TI  - Evidence-based clinical practice for the neurointerventionalist.
AB  - The field of neurointerventional (NI) surgery has developed in the context of
      technologic innovation. Many treatments readily provided in 2014 would have been
      hard to imagine as recently as 10 years ago. The reality of present day NI care
      is that, while providers, payors, policy makers and patients rely on evidence to
      guide NI decision-making, the available data are often less robust than
      participants might desire. In this paper we will explore the fundamentals of
      evidence-based clinical practice.

PMID- 24578481
TI  - How does elective laparoscopic abdominal aortic aneurysm repair compare to
      endovascular aneurysm repair?
AB  - A best evidence topic in surgery was written according to a structured protocol.
      The question addressed was how elective laparoscopic abdominal aortic aneurysm
      (AAA) repair compared to endovascular aneurysm repair (EVAR) in terms of
      survival. There were 229 papers found using the reported search, with 8 papers (5
      prospective studies, 1 retrospective study, 1 randomized trial and 1 systematic
      review) representing the best evidence to answer the question proposed. Current
      evidence suggests that EVAR is the preferred surgical approach for AAA repair,
      due to shorter hospital stay and lower perioperative morbidity and mortality
      rates, as opposed to an open surgical approach. Despite this, EVAR is subject to
      a number of limitations, including device restrictions in patients with
      anatomical variations as well as increased risk of future complications stemming
      from device implantation. We discuss a key study that showed that complications
      in the EVAR group commonly included endoleak type II and graft thrombosis. More
      importantly, there were similar rates of complications between those patients
      receiving EVAR and those receiving minimally invasive aortic surgery. The
      evidence suggests that elective laparoscopic AAA repair has a favourable safety
      profile comparable with that of EVAR, with low conversion rates as well as
      similar mortality and morbidity rates. This has been illustrated in several
      studies. We discuss a prospective randomized trial of 100 patients, which
      compared EVAR with hand-assisted laparoscopic surgery. This study showed no
      deaths in either group after the procedure or at follow-up after 12 months, with
      similar complication rates between the groups. While the evidence suggests that
      EVAR is less invasive, it does not always significantly alter the postoperative
      course or length of hospital stay for patients. We conclude from the evidence
      available that elective laparoscopic AAA repair may have a role in those patients
      who are unsuitable for EVAR. Unfortunately, few studies exist directly comparing
      these two techniques, and those that do are subject to limitations, for example,
      study population bias, small sample sizes and a lack of comparison in the
      literature between the common AAA repair techniques.

PMID- 24578483
TI  - Endovascular treatment for M2 occlusions in the era of stentrievers: a
      descriptive multicenter experience.
AB  - BACKGROUND: Patients with M2 middle cerebral artery (MCA) occlusions are not
      always considered for endovascular treatment. OBJECTIVE: To study outcomes in
      patients with M2 occlusion treated with endovascular procedures in the era of
      stentrievers. METHODS: We studied patients prospectively included in the SONIIA
      registry (years 2011-2012)-a mandatory, externally audited registry that monitors
      the quality of reperfusion therapies in Catalonia in routine practice. Good
      recanalization was defined as postprocedure Thrombolysis in Cerebral Infarction
      (TICI) score 2b-3; dramatic recovery as drop in National Institutes of Health
      Stroke Scale (NIHSS) score >10 points or NIHSS score <2 at 24-36 h; and good
      outcome as modified Rankin score (mRS) 0-2 at 3months. A 24 h CT scan determined
      symptomatic intracranial hemorrhage (SICH) and infarct volume. RESULTS: Of 571
      patients who received endovascular treatment, 65 (11.4%) presented an M2
      occlusion on initial angiogram, preprocedure NIHSS 16 (IQR 6). Mean time from
      symptom onset to groin puncture was 289 +/- 195 min. According to
      interventionalist preferences 86.2% (n=56) were treated with stentrievers (n=7 in
      combination with intra-arterial tissue plasminogen activator (tPA), 4.6% (n=3)
      received intra-arterial tPA only, and 9.2% (n=6) diagnostic angiography only.
      Good recanalization (78.5%) was associated with dramatic improvement (48% vs
      14.8%; p=0.02), smaller infarct volumes (8 vs 82 cc; p=0.01) and better outcome
      (mRS 0-2: 66.3% vs 30%; p=0.03). SICH (9%) was not associated with treatment
      modality or device used. After adjusting for age and preprocedure NIHSS, good
      recanalization emerged as an independent predictor of dramatic improvement
      (OR=5.9 (95% CI 1.2 to 29.2), p=0.03). Independent predictors of good outcome at
      3 months were age ( OR=1.067 (95% CI 1.005 to 1132), p=0.03) and baseline NIHSS (
      OR=1.162 (95% CI 1.041 to 1.297), p<0.01). CONCLUSIONS: Endovascular treatment of
      M2 MCA occlusion with stentrievers seems safe. Induced recanalization may double
      the chances of achieving a favorable outcome, especially for patients with
      moderate or severe deficit.

PMID- 24578484
TI  - Pipeline Embolization Device as primary treatment for blister aneurysms and
      iatrogenic pseudoaneurysms of the internal carotid artery.
AB  - BACKGROUND: Blood blister type aneurysms (BBAs) and pseudoaneurysms create a
      unique treatment challenge. Despite many advances in open surgical and
      endovascular techniques, this subset of patients retains relatively high rates of
      morbidity and mortality. Recently, BBAs have been treated with flow-diverting
      stents such as the Pipeline Embolization Device (PED) with overall positive
      results. METHODS: Four patients presented with dissecting internal carotid artery
      (ICA) aneurysms treated with the PED (two BBAs presenting with subarachnoid
      hemorrhage (SAH), two pseudoaneurysms after injury during endoscopic trans
      sphenoidal tumor surgery). RESULTS: Three patients had a successful angiographic
      and neurological outcome. One patient with a BBA re-ruptured during initial PED
      placement, again in the postoperative period, and later died. Primary PED
      treatment involved telescoping stents in two patients and coil embolization
      supplementation in one patient. CONCLUSIONS: The PED should be used selectively
      in the setting of acute SAH. Dual antiplatelet therapy can complicate
      hydrocephalus management, and the lack of immediate aneurysm occlusion creates
      the risk of short-term re-rupture. PED treatment for iatrogenic ICA
      pseudoaneurysms can provide a good angiographic and neurological outcome.

PMID- 24578486
TI  - Predicting parent vessel patency and treatment durability: a proposed grading
      scheme for the immediate angiographic results following Onyx HD-500 embolization
      of intracranial aneurysms.
AB  - INTRODUCTION: Onyx HD-500 embolization of intracranial aneurysms leads to high
      rates of complete and durable occlusion. However, little information exists as to
      what constitutes an optimal immediate angiographic result. We devised a simple
      grading scheme based on the pattern of parent artery and aneurysm neck
      reconstruction, and correlated it with long term outcome. METHODS: All cases of
      Onyx embolization for unruptured aneurysms performed between September 2008 and
      April 2010 were retrospectively reviewed. Immediate angiographic results were
      categorized according to the pattern of extra-aneurysmal Onyx leakage: grade A,
      none; grade B, 'hat brim' lamination; and grade C, 'ectopic' Onyx (C1, non-flow
      limiting; C2, flow limiting). Results of follow-up vascular imaging were reviewed
      and correlated with the angiographic grade. RESULTS: 24 embolization procedures
      were performed in 21 patients with 23 aneurysms. Aneurysm size ranged from 2.5 to
      24 mm and neck width from 2 to 8 mm. Complete occlusion was achieved in 20 cases
      (83.3%) and subtotal occlusion in three (12.5%). Immediate angiographic results
      were: grade A in ten (41.7%), grade B in eight (33.3%), and grade C in six (25%).
      Stable angiographic results were seen in 85%, 94%, 94%, and 100% at 6, 12, 24,
      and 36 months, respectively. Angiographic recurrence was observed in four cases
      (16.7%), all grade A (p=0.006). Delayed parent vessel occlusion occurred in two
      cases (8.3%), both grade C2 (p=0.014). CONCLUSIONS: This simple grading system
      may help predict long term angiographic results. Hat brim Onyx lamination seems
      to provide an optimal balance between treatment durability and parent vessel
      patency. Prospective validation is warranted.

PMID- 24578485
TI  - Endovascular treatment of tandem vascular occlusions in acute ischemic stroke.
AB  - BACKGROUND AND PURPOSE: Tandem vascular occlusions are an important cause of
      acute ischemic stroke (AIS) and present unique treatment challenges. We report
      our experience of managing a subset of AIS patients with extracranial vascular
      stenting/angioplasty and intracranial revascularization. METHODS: Consecutive
      patients who presented at three centers with AIS from tandem vascular occlusions
      confirmed by brain and neck CT imaging were included in the study. We
      retrospectively analyzed the patient demographics, National Institute of Health
      Stroke Scale (NIHSS) score and modified Rankin Scale (mRS) score at the time of
      admission, treatment strategy, angiographic results using the Thrombolysis In
      Cerebral Infarction (TICI) score, and clinical and imaging follow-up. RESULTS:
      Twenty-eight patients were included. The mean NIHSS score at admission was 18.
      Extracranial carotid occlusions with a concomitant middle cerebral artery
      occlusion were seen in 89.3% of patients (n=25) and vertebral artery combined
      with basilar artery lesions in 10.7% (n=3). An antegrade approach (ie, treatment
      of the extracranial lesion first) was used in 24 patients (85.7%). Proximal
      occlusion recanalization was achieved usually with a stent (n=27; 96.4%).
      Pursuant to intracranial revascularization techniques, >= TICI 2A recanalization
      was seen in 96.4% of patients. An mRS score of <= 2 at 90 days was achieved in
      56.5% of patients. CONCLUSIONS: Our study shows preliminary data from three
      centers on recanalization of tandem occlusions in patients presenting with AIS.
      There was a preference to revascularize the proximal occlusion using a stent
      followed by distal recanalization with mechanical thrombectomy, intra-arterial
      thrombolysis or a combination of these. This approach has low periprocedural
      complications and can achieve an excellent angiographic and clinical outcome.

PMID- 24578487
TI  - Seonamhaeicola aphaedonensis gen. nov., sp. nov., a member of the family
      Flavobacteriaceae isolated from a tidal flat sediment.
AB  - A Gram-stain-negative, non-motile, rod-shaped bacterial strain, AH-M5(T), which
      was isolated from a tidal flat sediment at Aphae Island in South Korea, was
      characterized taxonomically. Strain AH-M5(T) grew optimally at 25  degrees C, at
      pH 7.0-8.0 and in presence of 2.0% (w/v) NaCl. Phylogenetic trees based on 16S
      rRNA gene sequences revealed that strain AH-M5(T) clustered coherently with the
      type strains of Mangrovimonas yunxiaonensis and Meridianimaribacter flavus,
      showing 93.4-94.3% sequence similarity. The novel strain exhibited 16S rRNA gene
      sequence similarity values of less than 93.4% to the type strains of other
      recognized species. Strain AH-M5(T) contained MK-6 as the predominant menaquinone
      and iso-C(15 : 1) G, iso-C(15 : 0), iso-C(17 : 0) 3-OH and summed feature 3 (C(16
      : 1)omega7c and/or C(16 : 1)omega6c) as the major fatty acids. The polar lipid
      profile of strain AH-M5(T) containing phosphatidylethanolamine and one
      unidentified lipid as major components was differentiated from those of the type
      strains of Mangrovimonas yunxiaonensis and Meridianimaribacter flavus. The DNA
      G+C content of strain AH-M5(T) was 34.8 mol%. Differential phenotypic properties,
      together with the phylogenetic and chemotaxonomic data, demonstrated that strain
      AH-M5(T) is distinguished from Mangrovimonas yunxiaonensis and
      Meridianimaribacter flavus. On the basis of the data presented, strain AH-M5(T)
      is considered to represent a novel genus and species within the family
      Flavobacteriaceae, for which the name Seonamhaeicola aphaedonensis gen. nov., sp.
      nov. is proposed. The type strain of the type species is AH-M5(T) ( = KCTC
      32578(T) = CECT 8487(T)).

PMID- 24578488
TI  - The effect of the psychosocial working environment on cognition and dementia.

PMID- 24578489
TI  - Monoclonal B-cell lymphocytosis in donors.

PMID- 24578490
TI  - Otlertuzumab more than a TRU(E) toddler in CLL?

PMID- 24578492
TI  - Honing in on the (epi)genetic basis of AITL.

PMID- 24578491
TI  - Optimizing tolerability of TKI therapy in CML.

PMID- 24578493
TI  - Oncolytic virotherapy for ALL: MSCs to the rescue.

PMID- 24578494
TI  - Iron-related adverse effects from stored blood.

PMID- 24578495
TI  - Reversing CD8+ T-cell exhaustion with DLI.

PMID- 24578496
TI  - Mystery solved: VSV-G-LVs do not allow efficient gene transfer into unstimulated
      T cells, B cells, and HSCs because they lack the LDL receptor.

PMID- 24578497
TI  - Statin and aspirin use is associated with improved outcome of FCR therapy in
      relapsed/refractory chronic lymphocytic leukemia.

PMID- 24578498
TI  - Mutations in GATA2 are rare in juvenile myelomonocytic leukemia.

PMID- 24578499
TI  - Does the haplotype Met408-Del420, which was apparently predictive for imatinib
      efficacy, really exist and how strongly may it affect OCT1 activity?

PMID- 24578500
TI  - Heckathorn disease revisited.

PMID- 24578501
TI  - Evidence-based organization and patient safety strategies in European hospitals.
AB  - OBJECTIVE: To explore how European hospitals have implemented patient safety
      strategies (PSS) and evidence-based organization of care pathway (EBOP)
      recommendations and examine the extent to which implementation varies between
      countries and hospitals. DESIGN: Mixed-method multilevel cross-sectional design
      in seven countries as part of the European Union-funded project 'Deepening our
      Understanding of Quality improvement in Europe' (DUQuE). SETTING AND
      PARTICIPANTS: Seventy-four acute care hospitals with 292 departments managing
      acute myocardial infarction (AMI), hip fracture, stroke, and obstetric
      deliveries. Main outcome measure Five multi-item composite measures-one generic
      measure for PSS and four pathway-specific measures for EBOP. RESULTS: Potassium
      chloride had only been removed from general medication stocks in 9.4-30.5% of
      different pathways wards and patients were adequately identified with wristband
      in 43.0-59.7%. Although 86.3% of areas treating AMI patients had immediate access
      to a specialist physician, only 56.0% had arrangements for patients to receive
      thrombolysis within 30 min of arrival at the hospital. A substantial amount of
      the total variance observed was due to between-hospital differences in the same
      country for PSS (65.9%). In EBOP, between-country differences play also an
      important role (10.1% in AMI to 57.1% in hip fracture). CONCLUSIONS: There were
      substantial gaps between evidence and practice of PSS and EBOP in a sample of
      European hospitals and variations due to country differences are more important
      in EBOP than in PSS, but less important than within-country variations. Agencies
      supporting the implementation of PSS and EBOP should closely re-examine the
      effectiveness of their current strategies.

PMID- 24578502
TI  - Advances in the treatment of hematologic malignancies using immunoconjugates.
AB  - Monoclonal antibody therapy has revolutionized cancer treatment by significantly
      improving patient survival both in solid tumors and hematologic malignancies.
      Recent technological advances have increased the effectiveness of immunotherapy
      leading to its broader application in diverse treatment settings.
      Immunoconjugates (ICs) consist of a cytotoxic effector covalently linked to a
      monoclonal antibody that enables the targeted delivery of its therapeutic payload
      to tumors based on cell-surface receptor recognition. ICs are classified into 3
      groups based on their effector type: immunotoxins (protein toxin),
      radioimmunoconjugates (radionuclide), and antibody drug conjugates (small
      molecule drug). Optimization of each individual component of an IC (antibody,
      linker, and effector) is essential for therapeutic efficacy. Clinical trials have
      been conducted to investigate the effectiveness of ICs in hematologic
      malignancies both as monotherapy and in multiagent regimens in
      relapsed/refractory disease as well as frontline settings. These studies have
      yielded encouraging results particularly in lymphoma. ICs comprise an exciting
      group of therapeutics that promise to play an increasingly important role in the
      management of hematologic malignancies.

PMID- 24578503
TI  - Immunotoxins for leukemia.
AB  - Unconjugated monoclonal antibodies that target hematopoietic differentiation
      antigens have been developed to treat hematologic malignancies. Although some of
      these have activity against chronic lymphocytic leukemia and hairy cell leukemia,
      in general, monoclonal antibodies have limited efficacy as single agents in the
      treatment of leukemia. To increase their potency, the binding domains of
      monoclonal antibodies can be attached to protein toxins. Such compounds, termed
      immunotoxins, are delivered to the interior of leukemia cells based on antibody
      specificity for cell surface target antigens. Recombinant immunotoxins have been
      shown to be highly cytotoxic to leukemic blasts in vitro, in xenograft model
      systems, and in early-phase clinical trials in humans. These agents will likely
      play an increasing role in the treatment of leukemia. 

PMID- 24578504
TI  - Antibody-modified T cells: CARs take the front seat for hematologic malignancies.
AB  - T cells redirected to specific antigen targets with engineered chimeric antigen
      receptors (CARs) are emerging as powerful therapies in hematologic malignancies.
      Various CAR designs, manufacturing processes, and study populations, among other
      variables, have been tested and reported in over 10 clinical trials. Here, we
      review and compare the results of the reported clinical trials and discuss the
      progress and key emerging factors that may play a role in effecting tumor
      responses. We also discuss the outlook for CAR T-cell therapies, including
      managing toxicities and expanding the availability of personalized cell therapy
      as a promising approach to all hematologic malignancies. Many questions remain in
      the field of CAR T cells directed to hematologic malignancies, but the
      encouraging response rates pave a wide road for future investigation.

PMID- 24578505
TI  - Two rice authentic histidine phosphotransfer proteins, OsAHP1 and OsAHP2, mediate
      cytokinin signaling and stress responses in rice.
AB  - Cytokinin plays an important role in plant development and stress tolerance.
      Studies of Arabidopsis (Arabidopsis thaliana) have demonstrated that cytokinin
      acts through a two-component system that includes a histidine (His) kinase, a His
      phosphotransfer protein (HP), and a response regulator. Phylogenetic analyses
      have revealed the conservation of His kinases but lineage-specific expansion of
      HPs and response regulators in rice (Oryza sativa). However, whether the
      functions of rice HPs have diverged remains unknown. In this study, two rice
      authentic HPs (OsAHP1 and OsAHP2) were knocked down simultaneously via RNA
      interference (RNAi), and the transgenic OsAHP-RNAi plants exhibited phenotypes
      expected for a deficiency in cytokinin signaling, including dwarfism with reduced
      internode lengths, enhanced lateral root growth, early leaf senescence, and
      reduced tiller numbers and fertility under natural conditions. The OsAHP-RNAi
      seedlings were also hyposensitive to exogenous cytokinin. Furthermore, OsAHP-RNAi
      seedlings were hypersensitive to salt treatment but resistant to osmotic stress
      relative to wild-type plants. These results indicate that OsAHPs function as
      positive regulators of the cytokinin signaling pathway and play different roles
      in salt and drought tolerance in rice. 

PMID- 24578509
TI  - Language tests for EU doctors set to start in June in UK.

PMID- 24578506
TI  - Stomatal size, speed, and responsiveness impact on photosynthesis and water use
      efficiency.
AB  - The control of gaseous exchange between the leaf and bulk atmosphere by stomata
      governs CO2 uptake for photosynthesis and transpiration, determining plant
      productivity and water use efficiency. The balance between these two processes
      depends on stomatal responses to environmental and internal cues and the
      synchrony of stomatal behavior relative to mesophyll demands for CO2. Here we
      examine the rapidity of stomatal responses with attention to their relationship
      to photosynthetic CO2 uptake and the consequences for water use. We discuss the
      influence of anatomical characteristics on the velocity of changes in stomatal
      conductance and explore the potential for manipulating the physical as well as
      physiological characteristics of stomatal guard cells in order to accelerate
      stomatal movements in synchrony with mesophyll CO2 demand and to improve water
      use efficiency without substantial cost to photosynthetic carbon fixation. We
      conclude that manipulating guard cell transport and metabolism is just as, if not
      more likely to yield useful benefits as manipulations of their physical and
      anatomical characteristics. Achieving these benefits should be greatly
      facilitated by quantitative systems analysis that connects directly the molecular
      properties of the guard cells to their function in the field.

PMID- 24578508
TI  - Divergent roles for maize PAN1 and PAN2 receptor-like proteins in cytokinesis and
      cell morphogenesis.
AB  - Pangloss1 (PAN1) and PAN2 are leucine-rich repeat receptor-like proteins that
      function cooperatively to polarize the divisions of subsidiary mother cells
      (SMCs) during stomatal development in maize (Zea mays). PANs colocalize in SMCs,
      and both PAN1 and PAN2 promote polarization of the actin cytoskeleton and nuclei
      in these cells. Here, we show that PAN1 and PAN2 have additional functions that
      are unequal or divergent. PAN1, but not PAN2, is localized to cell plates in all
      classes of dividing cells examined. pan1 mutants exhibited no defects in cell
      plate formation or in the recruitment or removal of a variety of cell plate
      components; thus, they did not demonstrate a function for PAN1 in cytokinesis.
      PAN2, in turn, plays a greater role than PAN1 in directing patterns of
      postmitotic cell expansion that determine the shapes of mature stomatal
      subsidiary cells and interstomatal cells. Localization studies indicate that PAN2
      impacts subsidiary cell shape indirectly by stimulating localized cortical actin
      accumulation and polarized growth in interstomatal cells. Localization of PAN1,
      Rho of Plants2, and PIN1a suggests that PAN2-dependent cell shape changes do not
      involve any of these proteins, indicating that PAN2 function is linked to actin
      polymerization by a different mechanism in interstomatal cells compared with
      SMCs. Together, these results demonstrate that PAN1 and PAN2 are not dedicated to
      SMC polarization but instead play broader roles in plant development. We
      speculate that PANs may function in all contexts to regulate polarized membrane
      trafficking either directly or indirectly via their influence on actin
      polymerization. 

PMID- 24578507
TI  - Cyanobacterial phytochrome2 regulates the heterotrophic metabolism and has a
      function in the heat and high-light stress response.
AB  - Cyanobacteria combine the photosynthetic and respiratory electron transport in
      one membrane system, the thylakoid membrane. This feature requires an elaborate
      regulation mechanism to maintain a certain redox status of the electron transport
      chain, hence allowing proper photosynthetic and respiratory energy metabolism. In
      this context, metabolic adaptations, as seen in the light-to-dark and dark-to
      light transitions, are particularly challenging. However, the molecular basis of
      the underlying regulatory mechanisms is not well-understood. Here, we describe a
      function of cyanobacterial phytochrome2 (Cph2), a phytochrome of the
      cyanobacterial model system Synechocystis sp. PCC 6803, in regulation of the
      primary energy metabolism. When cells are shifted from photoautotrophic
      planktonic growth to light-activated heterotrophic growth and biofilm initiation,
      knockout of Cph2 results in impaired growth, a decrease in the activity of Glc-6
      P dehydrogenase, a decrease of the transcript abundance/activity of cytochrome-c
      oxidase, and slower phycocyanin degradation. Measurements of the plastoquinone
      reduction confirm an impaired heterotrophic metabolism in the cph2 knockout. When
      cells that were adapted to heterotrophic metabolism are shifted back to light
      conditions, the knockout of Cph2 results in an altered photosystem II chlorophyll
      fluorescence induction curve, which is indicative of an impaired redox balance of
      the electron transport chain. Moreover, Cph2 plays a role in the heat and high
      light stress response, particularly under photomixotrophic conditions. Our
      results show a function of Cph2 in the adaptation of the primary energy
      metabolism to changing trophic conditions. The physiological role of Cph2 in
      biofilm formation is discussed. 

PMID- 24578511
TI  - Signal or noise, a statistical perspective.

PMID- 24578512
TI  - Geriatrician questions prescribing for stroke prevention in people over 80.

PMID- 24578510
TI  - Prep1 and Meis1 competition for Pbx1 binding regulates protein stability and
      tumorigenesis.
AB  - Pbx-regulating protein-1 (Prep1) is a tumor suppressor, whereas myeloid ecotropic
      viral integration site-1 (Meis1) is an oncogene. We show that, to perform these
      activities in mouse embryonic fibroblasts, both proteins competitively
      heterodimerize with pre-B-cell leukemia homeobox-1 (Pbx1). Meis1 alone transforms
      Prep1-deficient fibroblasts, whereas Prep1 overexpression inhibits Meis1
      tumorigenicity. Pbx1 can, therefore, alternatively act as an oncogene or tumor
      suppressor. Prep1 posttranslationally controls the level of Meis1, decreasing its
      stability by sequestering Pbx1. The different levels of Meis1 and the presence of
      Prep1 are followed at the transcriptional level by the induction of specific
      transcriptional signatures. The decrease of Meis1 prevents Meis1 interaction with
      Ddx3x and Ddx5, which are essential for Meis1 tumorigenesis, and modifies the
      growth-promoting DNA binding landscape of Meis1 to the growth-controlling
      landscape of Prep1. Hence, the key feature of Prep1 tumor-inhibiting activity is
      the control of Meis1 stability. 

PMID- 24578513
TI  - Medical student views on the use of Facebook profile screening by residency
      admissions committees.
AB  - PURPOSE: Previous research has shown that >50% of residency programmes indicate
      that inappropriate Facebook postings could be grounds for rejecting a student
      applicant. This study sought to understand medical students' views regarding the
      impact of their Facebook postings on the residency admissions process. STUDY
      DESIGN: In 2011-2012, we conducted a national survey of 7144 randomly selected
      medical students representing 10% of current enrollees in US medical schools.
      Students were presented with a hypothetical scenario of a residency admissions
      committee searching Facebook and finding inappropriate pictures of a student, and
      were asked how the committee ought to regard these pictures. RESULTS: The
      response rate was 30% (2109/7144). Respondents did not differ from medical
      students nationally with regard to type of medical school and regional
      representation. Of the three options provided, the majority of respondents
      (63.5%) indicated 'the pictures should be considered along with other factors,
      but should not be grounds for automatic rejection of the application'. A third
      (33.7%) believed 'the pictures should have no bearing on my application; the
      pictures are irrelevant'. A small minority of respondents (2.8%) felt 'the
      pictures should be grounds for automatic rejection of the application'.
      CONCLUSIONS: That the views of students regarding the consequences of their
      online activity differ so greatly from the views of residency admissions
      committees speaks to the need for better communication between these parties. It
      also presents opportunities for medical schools to help students in their
      residency application process by increasing awareness of social media screening
      strategies used by some residency programmes, and fostering self-awareness around
      the use of social media during medical school and especially during the residency
      application process.

PMID- 24578514
TI  - Screening for meticillin resistant Staphylococcus aureus (MRSA): who, when, and
      how?

PMID- 24578515
TI  - Increased heart attacks in men using testosterone: the UK importantly lags far
      behind the US in prescribing testosterone.

PMID- 24578516
TI  - We need a global system to help identify new uses for existing drugs.

PMID- 24578517
TI  - NHS England's plans to cut specialised service providers from 270 to under 30
      might not be "sensible," conference hears.

PMID- 24578518
TI  - Behavioral health admissions in Massachusetts show no rise despite new coverage
      for young people.

PMID- 24578519
TI  - Mid Staffordshire hospital trust's services will be divided between two
      neighbouring hospitals.

PMID- 24578520
TI  - Safe patient handling perceptions and practices: a survey of acute care physical
      therapists.
AB  - BACKGROUND: Acute care physical therapists are at risk for developing work
      related musculoskeletal disorders (WMSDs) due to manual patient handling. Safe
      patient handling (SPH) reduces WMSDs caused by manual handling. OBJECTIVE: The
      purpose of this study was to describe the patient handling practices of acute
      care physical therapists and their perceptions regarding SPH. Additionally, this
      study determined whether an SPH program influences the patient handling practices
      and perceptions regarding SPH of acute care physical therapists. METHODS:
      Subscribers to the electronic discussion board of American Physical Therapy
      Association's Acute Care Section were invited to complete a survey questionnaire.
      RESULTS: The majority of respondents used SPH equipment and practices (91.1%),
      were confident using SPH equipment and practices (93.8%), agreed that evidence
      supports the use of SPH equipment and practices (87.0%), and reported the use of
      SPH equipment and practices is feasible (92.2%). Respondents at a facility with
      an SPH program were more likely to use SPH equipment and practices, have received
      training in the use of SPH equipment and practices, agree that the use of SPH
      equipment and practices is feasible, and feel confident using SPH equipment and
      practices. LIMITATIONS: The study might not reflect the perceptions and practices
      of the population of acute care physical therapists. CONCLUSION: Acute care
      physical therapists are trained to use SPH equipment and practices, use SPH
      equipment and practices, and have positive perceptions regarding SPH. Acute care
      physical therapists in a facility with an SPH program are more likely to use SPH
      equipment and practices, receive training in SPH equipment and practices, and
      have positive perceptions regarding SPH. Quasi-regulatory organizations should
      incorporate SPH programs into their evaluative standards.

PMID- 24578521
TI  - Muscle atrophy, voluntary activation disturbances, and low serum concentrations
      of IGF-1 and IGFBP-3 are associated with weakness in people with chronic stroke.
AB  - BACKGROUND: The muscle weakness that is exhibited poststroke is due to a
      multifactorial etiology involving the central nervous system and skeletal muscle
      changes. Insulinlike growth factor 1 (IGF-1) and IGF binding protein 3 (IGFBP-3)
      have been described as biomarkers of neuromuscular performance in many
      conditions. However, no information about these biomarkers is available for
      people with chronic hemiparesis. OBJECTIVE: The purpose of this study was to
      investigate possible factors involved in muscle weakness, such as IGF-1 and IGFBP
      3 serum concentrations, muscle volume, and neuromuscular performance of the knee
      flexors and extensors, in people with chronic hemiparesis poststroke. DESIGN:
      This was a cross-sectional study. METHODS: A cross-sectional study was performed
      on 14 individuals poststroke who were paired with healthy controls. Mobility,
      function, balance, and quality of life were recorded as outcome measures. Knee
      flexor and extensor muscle volumes and neuromuscular performance were measured
      using nuclear magnetic resonance imaging, dynamometry, and electromyography. The
      serum concentrations of IGF-1 and IGFBP-3 were quantified by enzyme-linked
      immunosorbent assay (ELISA). RESULTS: The hemiparetic group had low serum
      concentrations of IGF-1 (25%) and IGFBP-3 (40%); reduced muscle volume in the
      vastus medialis (32%), vastus intermedius (29%), biceps femoris (16%), and
      semitendinosus and semimembranosus (12%) muscles; reduced peak torque, power, and
      work of the knee flexors and extensors; and altered agonist and antagonist muscle
      activation compared with controls. CONCLUSIONS: Low serum concentrations of IGF-1
      and IGFBP-3, deficits in neuromuscular performance, selective muscle atrophy, and
      decreased agonist muscle activation were found in the group with chronic
      hemiparesis poststroke. Both hemorrhagic and ischemic stroke were considered, and
      the data reflect a chronic poststroke population with good function.

PMID- 24578523
TI  - Overweight children could become the "new norm" for Europe, WHO says.

PMID- 24578522
TI  - Relationship between lower extremity muscle strength and all-cause mortality in
      Japanese patients undergoing dialysis.
AB  - BACKGROUND: Skeletal muscle wasting is common and insidious in patients who are
      undergoing hemodialysis. However, the association between lower extremity muscle
      strength and all-cause mortality remains unclear in this population. OBJECTIVE:
      The purpose of this study was to investigate the prognostic significance of lower
      extremity muscle strength on 7-year survival in a cohort of patients who were
      clinically stable and undergoing hemodialysis. DESIGN: A prospective cohort study
      was conducted. METHODS: A total of 190 Japanese outpatients who were undergoing
      maintenance hemodialysis 3 times per week at a hemodialysis center were followed
      for up to 7 years. Lower extremity muscle strength was evaluated using a handheld
      dynamometer at the time of patient enrollment in the study. Muscle strength data
      were divided by dry weight and expressed as a percentage. A Cox proportional
      hazards regression model was used to assess the contribution of lower extremity
      muscle strength to all-cause mortality. RESULTS: The median age (25th and 75th
      percentiles) of this study population was 64 years (57 and 72 years), 53.2% of
      the patients were women, and the time on hemodialysis was 39.0 months (15.9 and
      110.5 months) at baseline. During a median follow-up of 36.0 months, there were
      30 deaths. With a multivariate Cox model, the hazard ratio in the group with a
      knee extensor strength of <40% was 2.73 (95% confidence interval=1.14-6.52)
      compared with that in the >=40% group. LIMITATIONS: This was a small-scale
      observational study, and the mechanisms underlying the higher mortality risk in
      patients with poor muscle strength undergoing hemodialysis than in other patients
      undergoing hemodialysis remain to be elucidated. CONCLUSIONS: Decreased lower
      extremity muscle strength was strongly associated with increased mortality risk
      in patients undergoing hemodialysis.

PMID- 24578525
TI  - Patients could withhold information from GPs because of confusion over care.data
      scheme, doctors warn.

PMID- 24578524
TI  - Medication errors: do they occur in isolation?

PMID- 24578526
TI  - Sarcoma of the lung.

PMID- 24578527
TI  - EURADOS IC2012N: EURADOS 2012 intercomparison for whole-body neutron dosimetry.
AB  - The European Radiation Dosimetry Group (EURADOS) IC2012n intercomparison for
      neutron dosemeters intended to measure personal dose equivalent, Hp(10), was
      performed in 2012. A total of 31 participants (27 individual monitoring services
      from Europe, 2 from Japan, 1 from Israel and 1 from USA) registered with 34
      dosimetry systems. Participation was restricted to passive or active neutron
      dosemeters routinely used in individual monitoring of radiation workers. The
      dosimetry systems were based on thermoluminescence, polyallyldiglycol carbonate,
      optically stimulated luminescence, fission track detection and silicon diodes
      (electronic devices). The irradiation tests were chosen to provide the
      participants with useful information on their dosimetry systems, i.e. linearity,
      reproducibility, responses for different energies and angles and to simulated
      workplace fields. The paper will report and discuss the first analysis of the
      results of the EURADOS IC2012n intercomparison. 

PMID- 24578528
TI  - A model study on the absorbed dose of radiation following respiratory intake of
      238U3O8 aerosols.
AB  - Aerosols of depleted uranium oxides, formed upon high-energy impact of shells on
      hard targets during military operations, are able to disperse, reach the alveolar
      region of the lungs and be absorbed and distributed throughout various parts of
      the body. The absorbed particles are subjected to clearance in the upper
      respiratory tract, distribution to other body districts, dissolution and
      excretion. While the soluble forms of uranium are known to deliver a small dose
      of radiation to the body due to their homogeneous distribution and the low
      specific activity of (238)U, ceramic particles exhibit a low dissolution rate and
      irradiate a limited volume of tissue for a long time with alpha particles with an
      energy of 4.267 MeV. The extent of the irradiated tissues depends on the radius
      of the particles and the total intake of uranium oxides. For the measured intake
      of U3O8 of a war veteran (15.51 MUg) the number of particles ranges from
      5.56*10(4) to 6.95*10(6) for sizes of 0.4-2.0 MUm. Modelling the distribution of
      the particles between two compartments of the body, the averaged dose absorbed in
      20 y by tissues surrounding the particles and within the range of the alpha
      particles varies from 6.8 mGy to 0.85 Gy for lungs and 8.1 mGy to 1.0 Gy for the
      lymph nodes, respectively. Correspondingly, due to the clearance and
      redistribution, the mass irradiated by 2.0-MUm particles falls in 20 y from 6.06
      mg to 0.94 MUg in the lungs and grows from 0 to 1.0 mg in the lymph nodes. The
      estimated rate of formation of hydroxyl radicals upon radiolysis of water in the
      lungs and lymph nodes is 5.17*10(4) d(-1) per cell after 1 y. 

PMID- 24578529
TI  - Changes in seismic anisotropy shed light on the nature of the Gutenberg
      discontinuity.
AB  - The boundary between the lithosphere and asthenosphere is associated with a
      platewide high-seismic velocity "lid" overlying lowered velocities, consistent
      with thermal models. Seismic body waves also intermittently detect a sharp
      velocity reduction at similar depths, the Gutenberg (G) discontinuity, which
      cannot be explained by temperature alone. We compared an anisotropic tomography
      model with detections of the G to evaluate their context and relation to the
      lithosphere-asthenosphere boundary (LAB). We find that the G is primarily
      associated with vertical changes in azimuthal anisotropy and lies above a
      thermally controlled LAB, implying that the two are not equivalent interfaces.
      The origin of the G is a result of frozen-in lithospheric structures, regional
      compositional variations of the mantle, or dynamically perturbed LAB. 

PMID- 24578531
TI  - Highly crystalline multimetallic nanoframes with three-dimensional
      electrocatalytic surfaces.
AB  - Control of structure at the atomic level can precisely and effectively tune
      catalytic properties of materials, enabling enhancement in both activity and
      durability. We synthesized a highly active and durable class of electrocatalysts
      by exploiting the structural evolution of platinum-nickel (Pt-Ni) bimetallic
      nanocrystals. The starting material, crystalline PtNi3 polyhedra, transforms in
      solution by interior erosion into Pt3Ni nanoframes with surfaces that offer three
      dimensional molecular accessibility. The edges of the Pt-rich PtNi3 polyhedra are
      maintained in the final Pt3Ni nanoframes. Both the interior and exterior
      catalytic surfaces of this open-framework structure are composed of the
      nanosegregated Pt-skin structure, which exhibits enhanced oxygen reduction
      reaction (ORR) activity. The Pt3Ni nanoframe catalysts achieved a factor of 36
      enhancement in mass activity and a factor of 22 enhancement in specific activity,
      respectively, for this reaction (relative to state-of-the-art platinum-carbon
      catalysts) during prolonged exposure to reaction conditions. 

PMID- 24578530
TI  - Highly multiplexed subcellular RNA sequencing in situ.
AB  - Understanding the spatial organization of gene expression with single-nucleotide
      resolution requires localizing the sequences of expressed RNA transcripts within
      a cell in situ. Here, we describe fluorescent in situ RNA sequencing (FISSEQ), in
      which stably cross-linked complementary DNA (cDNA) amplicons are sequenced within
      a biological sample. Using 30-base reads from 8102 genes in situ, we examined RNA
      expression and localization in human primary fibroblasts with a simulated wound
      healing assay. FISSEQ is compatible with tissue sections and whole-mount embryos
      and reduces the limitations of optical resolution and noisy signals on single
      molecule detection. Our platform enables massively parallel detection of genetic
      elements, including gene transcripts and molecular barcodes, and can be used to
      investigate cellular phenotype, gene regulation, and environment in situ. 

PMID- 24578533
TI  - Super-Eddington mechanical power of an accreting black hole in M83.
AB  - Mass accretion onto black holes releases energy in the form of radiation and
      outflows. Although the radiative flux cannot substantially exceed the Eddington
      limit, at which the outgoing radiation pressure impedes the inflow of matter, it
      remains unclear whether the kinetic energy flux is bounded by this same limit.
      Here, we present the detection of a radio-optical structure, powered by outflows
      from a non-nuclear black hole. Its accretion disk properties indicate that this
      black hole is less than 100 solar masses. The optical-infrared line emission
      implies an average kinetic power of 3 * 10(40) erg second(-1), higher than the
      Eddington luminosity of the black hole. These results demonstrate kinetic power
      exceeding the Eddington limit over a sustained period, which implies greater
      ability to influence the evolution of the black hole's environment. 

PMID- 24578532
TI  - Structure of human RNase L reveals the basis for regulated RNA decay in the IFN
      response.
AB  - One of the hallmark mechanisms activated by type I interferons (IFNs) in human
      tissues involves cleavage of intracellular RNA by the kinase homology
      endoribonuclease RNase L. We report 2.8 and 2.1 angstrom crystal structures of
      human RNase L in complexes with synthetic and natural ligands and a fragment of
      an RNA substrate. RNase L forms a crossed homodimer stabilized by ankyrin (ANK)
      and kinase homology (KH) domains, which positions two kinase extension nuclease
      (KEN) domains for asymmetric RNA recognition. One KEN protomer recognizes an
      identity nucleotide (U), whereas the other protomer cleaves RNA between
      nucleotides +1 and +2. The coordinated action of the ANK, KH, and KEN domains
      thereby provides regulated, sequence-specific cleavage of viral and host RNA
      targets by RNase L. 

PMID- 24578534
TI  - Prevalence and trend of dyslipidaemia from 1996 to 2006 among normal and
      overweight adolescents in Taiwan.
AB  - OBJECTIVES: To evaluate the trend of dyslipidaemia from 1996 to 2006 and examine
      its relationship with weight status among adolescents in Taiwan. DESIGN: 2 cross
      sectional surveys were conducted in 1996 and 2006. SETTING: The junior high
      schools in Taipei. PARTICIPANTS: After multistage sampling, total of 1500 and
      1283 junior high school students were chosen in 1996 and 2006. After excluding
      missing data, a total of 1353 (676 boys and 677 girls) and 1203 (585 boys and 618
      girls) children were included in the final analyses in 1996 and 2006. OUTCOME
      MEASURES: Anthropometric measures as body height and weight were measured, and
      body mass index (BMI) was calculated. Blood lipid profiles as total cholesterol,
      triglyceride, high-density lipoprotein cholesterol (HDL-C) and low-density
      lipoprotein cholesterol were measured. RESULTS: From 1996 to 2006, the prevalence
      of dyslipidaemia and hypercholesterolaemia significantly increased from 13% (95%
      CI 11.3% to 15.0%) to 22.3% (95% CI 20.0% to 24.7%) and 6.2% (95% CI 5.0% to
      7.6%) to 13.8% (95% CI 11.9% to 15.9%), respectively. The prevalence of
      hypertriglyceridaemia and low HDL-C dyslipidaemia increased from 3% (95% CI 1.8%
      to 4.5%) to 4.3% (95% CI 2.8% to 6.2%) and 6.5% (95% CI 4.8% to 8.6%) to 11.6%
      (95% CI 9.1% to 14.5%), with significance seen only in boys. When compared with
      normal weight participants, overweight boys and girls faced a 2-fold and 1.6-fold
      increased risk of dyslipidaemia, respectively, in the 2006 study. The increased
      risk of low HDL-C dyslipidaemia for overweight participants was 2.6-fold and 7.2
      fold in boys and girls, respectively. In 2006, each unit increment of BMI was
      associated with 28%, 13% and 13% risk of hypertriglyceridaemia, low HDL-C and
      dyslipidaemia for boys, and 25% risk of low HDL-C dyslipidaemia in girls.
      CONCLUSIONS: The prevalence of dyslipidaemia had increased significantly for boys
      and girls in normal weight and overweight adolescents. Early screening of
      dyslipidaemia and weight intervention programmes in adolescents will be the key
      to prevent dyslipidaemia and cardiovascular-related comorbidities.

PMID- 24578535
TI  - Obesity in pregnancy: a retrospective prevalence-based study on health service
      utilisation and costs on the NHS.
AB  - OBJECTIVE: To estimate the direct healthcare cost of being overweight or obese
      throughout pregnancy to the National Health Service in Wales. DESIGN:
      Retrospective prevalence-based study. SETTING: Combined linked anonymised
      electronic datasets gathered on a cohort of women enrolled on the Growing Up in
      Wales: Environments for Healthy Living (EHL) study. Women were categorised into
      two groups: normal body mass index (BMI; n=260) and overweight/obese (BMI>25;
      n=224). PARTICIPANTS: 484 singleton pregnancies with available health service
      records and an antenatal BMI. PRIMARY OUTCOME MEASURE: Total health service
      utilisation (comprising all general practitioner visits and prescribed
      medications, inpatient admissions and outpatient visits) and direct healthcare
      costs for providing these services in the year 2011-2012. Costs are calculated as
      cost of mother (no infant costs are included) and are related to health service
      usage throughout pregnancy and 2 months following delivery. RESULTS: There was a
      strong association between healthcare usage cost and BMI (p<0.001). Adjusting for
      maternal age, parity, ethnicity and comorbidity, mean total costs were 23% higher
      among overweight women (rate ratios (RR) 1.23, 95% CI 1.230 to 1.233) and 37%
      higher among obese women (RR 1.39, 95% CI 1.38 to 1.39) compared with women with
      normal weight. Adjusting for smoking, consumption of alcohol, or the presence of
      any comorbidities did not materially affect the results. The total mean cost
      estimates were L3546.3 for normal weight, L4244.4 for overweight and L4717.64 for
      obese women. CONCLUSIONS: Increased health service usage and healthcare costs
      during pregnancy are associated with increasing maternal BMI; this was apparent
      across all health services considered within this study. Interventions costing
      less than L1171.34 per person could be cost-effective if they reduce healthcare
      usage among obese pregnant women to levels equivalent to that of normal weight
      women.

PMID- 24578536
TI  - Warfarin treatment among Finnish patients with atrial fibrillation: retrospective
      registry study based on primary healthcare data.
AB  - OBJECTIVE: To assess the frequency of warfarin use, the achieved international
      normalised ratio (INR) balance among warfarin users and the primary healthcare
      outpatient costs of patients with atrial fibrillation (AF). DESIGN:
      Retrospective, non-interventional registry study. SETTING: Primary healthcare.
      PARTICIPANTS: All patients with AF (n=2746) treated in one Finnish health centre
      between October 2010 and March 2012. METHODS: Data on healthcare resource use,
      warfarin use, individually defined target INR range and INR test results were
      collected from the primary healthcare database for patients with AF diagnosis.
      The analysed dataset consisted of a 1-year follow-up. Warfarin treatment balance
      was estimated with the proportion of time spent in the therapeutic INR range
      (TTR). The cost of used healthcare resources was valued separately with national
      and service provider unit costs to estimate the total outpatient treatment costs.
      The factors potentially impacting the treatment costs were assessed with a
      generalised linear regression model. RESULTS: Approximately 50% of the patients
      with AF with CHADS-VASc >=1 used warfarin. The average TTR was 65.2% but
      increased to 74.5% among patients using warfarin continuously (ie, without gaps
      exceeding 56 days between successive INR tests) during follow-up. One-third of
      the patients had a TTR of below 60%. The average outpatient costs in the patient
      cohort were ?314.44 with the national unit costs and ?560.26 with the service
      provider unit costs. The costs among warfarin users were, on average, ?524.11 or
      ?939.54 higher compared with the costs among non-users, depending on the used
      unit costs. A higher TTR was associated with lower outpatient costs. CONCLUSIONS:
      The patients in the study centre using warfarin were, on average, well controlled
      on warfarin, yet one-third of patients had a TTR of below 60%.

PMID- 24578537
TI  - Oral administration of herbal medicines for the treatment of otitis media with
      effusion: protocol for a systematic review.
AB  - INTRODUCTION: The purpose of this systematic review is to investigate the
      efficacy of the oral administration of herbal medicines for otitis media with
      effusion through analysing trial data. METHODS AND ANALYSIS: Electronic searches
      of the following 11 databases will be performed: MEDLINE, CINAHL, EMBASE, AMED,
      the Cochrane CENTRAL, 3 Chinese databases (CNKI, Wangfang Data and VIP
      Information) and 5 Korean databases (KoreaMed, Research Information Service
      System, Korea Studies Information System, Oriental Medicine Advanced Searching
      Integrated System (OASIS) and DBpia). The selection of the studies, data
      abstraction and validations will be performed independently by two researchers.
      DISSEMINATION: The systematic review will be published in a peer-reviewed
      journal. The review will also be disseminated electronically and in print. The
      review will be updated to inform and guide healthcare practice and policy. TRIAL
      REGISTRATION NUMBER: PROSPERO 2013: CRD42013005430.

PMID- 24578538
TI  - PARK2 and proinflammatory/anti-inflammatory cytokine gene interactions contribute
      to the susceptibility to leprosy: a case-control study of North Indian
      population.
AB  - OBJECTIVES: Cytokines and related molecules in immune-response pathways seem
      important in deciding the outcome of the host-pathogen interactions towards
      different polar forms in leprosy. We studied the role of significant and
      functionally important single-nucleotide polymorphisms (SNPs) in these genes,
      published independently from our research group, through combined interaction
      with an additional analysis of the in silico network outcome, to understand how
      these impact the susceptibility towards the disease, leprosy. DESIGN: The study
      was designed to assess an overall combined contribution of significantly
      associated individual SNPs to reflect on epistatic interactions and their outcome
      in the form of the disease, leprosy. Furthermore, in silico approach was adopted
      to carry out protein-protein interaction study between PARK2 and
      proinflammatory/anti-inflammatory cytokines. SETTING: Population-based case
      control study involved the data of North India. Protein-protein interaction
      networks were constructed using cytoscape. PARTICIPANTS: Study included the data
      available from 2305 Northern Indians samples (829 patients with leprosy; 1476
      healthy controls), generated by our research group. PRIMARY AND SECONDARY OUTCOME
      MEASURES: For genotype interaction analysis, all possible genotype combinations
      between selected SNPs were used as an independent variable, using binary logistic
      regression with the forward likelihood ratio method, keeping the gender as a
      covariate. RESULTS: Interaction analysis between PARK2 and significant SNPs of
      anti-inflammatory/proinflammatory cytokine genes, including BAT1 to BTNL2-DR
      spanning the HLA (6p21.3) region in a case-control comparison, showed that the
      combined analysis of: (1) PARK2, tumour necrosis factor (TNF), BTNL2-DR,
      interleukin (IL)-10, IL-6 and TGFBR2 increased the risk towards leprosy
      (OR=2.54); (2) PARK2, BAT1, NFKBIL1, LTA, TNF-LTB, IL12B and IL10RB provided
      increased protection (OR=0.26) in comparison with their individual contribution.
      CONCLUSIONS: Epistatic SNP-SNP interactions involving PARK2 and cytokine genes
      provide an additive risk towards leprosy susceptibility. Furthermore, in silico
      protein-protein interaction of PARK2 and important proinflammatory/anti
      inflammatory molecules indicate that PARK2 is central to immune regulation,
      regulating the production of different cytokines on infection.

PMID- 24578539
TI  - A cross-sectional study to compare two blood collection methods: direct venous
      puncture and peripheral venous catheter.
AB  - OBJECTIVES: To demonstrate the equivalence between blood collection methods using
      direct venous puncture (DVP) and a peripheral venous catheter or cannula (PVC).
      DESIGN AND SETTING: A cross-sectional study of simple crossover design with
      within-subject measures carried out between October 2011 and May 2012 at a
      regional hospital in Spain. PARTICIPANTS: 272 patients aged 18 or older
      hospitalised or admitted to the short-stay unit (SSU) who required laboratory
      testing and PVC to administer saline solution, intravenous fluid therapy and/or
      intravenous medication. Excluded were those with PVC collection time exceeding 20
      s, difficulty of venoclysis, or who presented with arteriovenous fistula,
      language difficulties, in critical condition or altered consciousness with no
      family to consent. PRIMARY AND SECONDARY OUTCOME MEASURES: 18 variables were
      recorded for DVP and PVC, along with age, sex, diagnosis, vein location for DVP,
      location of the PVC, PVC calibre, saline syringe, intravenous fluid therapy,
      medication, haemolysis and clotted blood during DVP or PVC collection. Univariate
      analysis, Pearson's product-moment correlation coefficient (r), Lin's concordance
      correlation coefficient (rc) and Bland-Altman's 95% agreement interval were
      provided. RESULTS: Included in the study were 272 patients, primarily aged 65 or
      older (80.9%), males (52.6%) and receiving intermittent medication (43.4%).
      Values obtained with both methods showed a positive linear association, being
      moderate for pO2 (r=0.405) and very high for all others (r>0.86). Levels were
      concordant (rc>=0.9), except for calcium (rc=0.860), pH (rc=0.853), pCO2
      (rc=0.843) and pO2 (rc=0.336) and equivalent for all determinations except pCO2
      and pO2, where clinically significant differences were found in more than 9% of
      cases (21.2%, 95% CI 16.6% to 26.5% and 73.1%, 95% CI 67.4% to 78.1%).
      CONCLUSIONS: Blood collection methods using DVP and PVC can be used
      interchangeably for most routine laboratory tests.

PMID- 24578540
TI  - Association of serum alkaline phosphatase with mortality in non-selected European
      patients with CKD5D: an observational, three-centre survival analysis.
AB  - OBJECTIVES: For characterisation of mineral bone disease in chronic kidney
      disease (CKD), laboratory surrogates have been suggested. This observational
      should investigate the association of total and skeletal alkaline phosphatase
      (AP) with mortality of patients undergoing maintenance renal replacement therapy.
      SETTING: Three renal outpatient centers in eastern-central Germany (secondary and
      tertiary care). PARTICIPANTS: Complete survival and laboratory datasets were
      available in 407 of 493 patients. Age and gender distribution was equivalent to a
      general population with end-stage CKD (CKD5D). Patients were included between
      2008 and 2010 if at least 2 weeks of maintenance treatment were documented.
      PRIMARY OUTCOME MEASURES: Mortality was estimated by setting the end of dialysis
      date as event date. Events other than death (change to another centre, life
      sustaining renal function or transplantation) were censored. RESULTS: The OR to
      die within follow-up for patients in the higher of two total AP strata was 2.70
      (95% CI 1.76 to 4.15). In univariate Kaplan-Meier analysis, total AP had a strong
      association with all-cause mortality (LogRank=24.1, p<0.001). Mean total AP and
      individual lowest skeletal AP, but not mean skeletal AP entered step-wise Cox
      models for survival from dialysis start (chi(2)=22.4; p<0.001) after adjusting
      for age, Kt/V, diabetes and vintage. Mean values of skeletal, total AP and
      parathyroid hormone were 14.8+/-8.9 ug/L, 91.9+/-55.3 U/L and 188+/-164 ng/L,
      respectively. Skeletal and total AP were highly correlated (R=0.86; p<0.001).
      CONCLUSIONS: This unselected CKD5D population exhibited a clinical significant
      association of total AP with crude mortality and a stronger death risk
      association of total AP and individual lowest skeletal AP with crude mortality.

PMID- 24578541
TI  - Measuring Armenia's progress on the Tobacco Control Scale: an evaluation of
      tobacco control in an economy in transition, 2005-2009.
AB  - OBJECTIVES: This study aimed to measure the 5-year progress in the implementation
      of WHO Framework Convention on Tobacco Control (FCTC) in Armenia by applying the
      Tobacco Control Scale, a rapid assessment tool developed to assess the strength
      of tobacco control policies in Europe. SETTING: Armenia, an economy in
      transition, has extreme smoking rates among men (62.5%) despite acceding to FCTC
      in 2004. However, little research has been carried out to evaluate Armenia's
      progress in tobacco control. METHODS: The Tobacco Control Scale total score was
      estimated for Armenia using the original methodology; however, a different source
      of data was used in estimating the subscores on tobacco price and tobacco control
      spending. RESULTS: Armenia's total score on Tobacco Control Scale has
      considerably improved from 2005 to 2009, mostly due to larger health warnings and
      advertising ban, and increased public spending on tobacco control. The scores for
      smoke-free public places, advertising ban, health warnings and treatment
      categories were below the European average in 2005 and 2007, while the price
      score was higher. Neither total tobacco control score nor any of its components
      showed a significant predictive value in a simple regression analysis using the
      total score and subscores as predictors for log-transformed per capita tobacco
      consumption. CONCLUSIONS: Higher than the European average price score for
      Armenia cannot be explained by the concept of affordability alone and may reflect
      a measurement error due to peculiarities of transition economies. The
      applicability of the Tobacco Control Scale could be limited to countries with
      mature economies, but not to transition countries such as Armenia with different
      social, political and economic environment. The scale modification, such as an
      adjustment for the policy enforcement and the effectiveness of public tobacco
      control spending along with alternative measures of affordability would be
      warranted to enhance its applicability in low-income and middle-income countries.

PMID- 24578542
TI  - Genetic polymorphism of NFKB1 and NFKBIA genes and liver cancer risk: a nested
      case-control study in Shanghai, China.
AB  - OBJECTIVES: Genetic variations of nuclear factor-kappaB (NF-kappaB) signalling
      pathway were found to be associated with inflammatory diseases and several
      malignancies. However, little is known about NF-kappaB pathway gene polymorphisms
      and susceptibility of liver cancer. The aim of this study was to investigate
      whether genetic variants of NFKB1 and NFKBIA were associated with risk of liver
      cancer in a Chinese population. DESIGN: The study was designed as a nested case
      control study within two prospective cohorts (the Shanghai Women's Health Study,
      SWHS, 1996-2000 and the Shanghai Men's Health Study, SMHS, 2002-2006). SETTINGS:
      This population-based study was conducted in urban Shanghai, China. PARTICIPANTS:
      A total of 217 incident liver cancer cases diagnosed through 31 December 2009 and
      427 healthy controls matched by sex, age at baseline (+/-2 years) and date (+/-30
      days) of sample collection were included in the study. PRIMARY AND SECONDARY
      OUTCOME MEASURES: Genetic polymorphisms of NFKB1 and NFKBIA were determined
      blindly by TaqMan single-nucleotide polymorphism (SNP) genotyping assay. OR and
      its 95% CIs were estimated by an unconditional logistic regression model to
      measure the association between selected SNPs and the risk of liver cancer.
      RESULTS: After adjusted for potential confounding factors, rs28362491 ins/del or
      del/del genotypes were associated with higher risk of liver cancer with an
      adjusted OR 1.54 (95% CI 1.04 to 2.28). rs230496 AG and GG genotypes were also
      noted with higher risk of liver cancer with an adjusted OR 1.53 (95% CI 1.03 to
      2.26). Haplotype analysis indicated that carriers of the NFKB1 GA and AA
      (rs230525-rs230530) haplotypes had higher risk of liver cancer under an additive
      model. No association was observed between NFKBIA variants and risk of live
      cancer. CONCLUSIONS: Our results suggest that genetic variants of NFKB1 influence
      liver cancer susceptibility in Chinese population, although replication in other
      studies is needed.

PMID- 24578544
TI  - Compensatory mechanisms in higher-educated subjects with Alzheimer's disease: a
      study of 20 years of cognitive decline.
AB  - A better knowledge of long-term trajectories of cognitive decline is a central
      feature of the study of the process leading to Alzheimer's dementia. Several
      factors may mitigate such decline, among which is education, a major risk factor
      for Alzheimer's disease. The aim of our work was to compare the pattern and
      duration of clinical trajectories before Alzheimer's dementia in individuals with
      low and high education within the PAQUID cohort involving 20 years of follow-up.
      The sample comprises 442 participants with incident Alzheimer's disease (27.2%
      were male)--171 with low education (mean age=86.2 years; standard deviation=5.3
      years) and 271 with higher education (mean age=86.5; standard deviation=5.4)--and
      442 control subjects matched according to age, sex and education. At each visit
      and up to the 20-year follow-up visit, several cognitive and clinical measures
      were collected and incident cases of Alzheimer's disease clinically diagnosed.
      The evolution of clinical measures in pre-demented subjects and matched controls
      was analysed with a semi-parametric extension of the mixed effects linear model.
      The results show that the first signs of cognitive decline occurred 15 to 16
      years before achieving dementia threshold in higher-educated subjects whereas
      signs occurred at 7 years before dementia in low-educated subjects. There seemed
      to be two successive periods of decline in higher-educated subjects. Decline
      started ~15 to 16 years before dementia with subtle impairment restricted to some
      cognitive tests and with no impact during the first 7 to 8 years on global
      cognition, cognitive complaints, or activities of daily living scales. Then, ~7
      years before dementia, global cognitive abilities begin to deteriorate, along
      with difficulties dealing with complex activities of daily living, the increase
      in self-perceived difficulties and depressive symptoms. By contrast, lower
      educated subjects presented a single period of decline lasting ~7 years,
      characterized by decline concomitantly affecting specific and more global
      cognitive function along with alteration in functional abilities. This study
      demonstrates how early cognitive symptoms may emerge preceding Alzheimer's
      dementia particularly in higher-educated individuals, for whom decline occurred
      up to 16 years before dementia. It also demonstrates the protective role of
      education in the clinical trajectory preceding Alzheimer's dementia. We suggest
      that the initial decline in cognition occurs at the onset of comparable
      Alzheimer's disease pathology in both groups, and is associated with immediate
      decline to dementia in the lower education group. In contrast, higher education
      protects against further cognitive decline for ~7 years until pathology becomes
      more severe.

PMID- 24578543
TI  - Benefits and barriers to participation in colorectal cancer screening: a protocol
      for a systematic review and synthesis of qualitative studies.
AB  - INTRODUCTION: Colorectal cancer (CRC) poses a serious health problem worldwide.
      While screening is effective in reducing CRC mortality, participation in
      screening tests is generally suboptimal and social inequities in participation
      are frequently reported. The goal of this review is to synthesise factors that
      influence an individual's decision to participate in CRC screening, and to
      explore how those factors vary by sex, ethnicity and socioeconomic status. DATA
      SOURCES: A primary search of Cumulative Index to Nursing and Allied Health
      Literature (CINAHL), MEDLINE, EMBASE, PsycINFO, and a secondary search of grey
      literature and articles taken from references of included articles (from
      inception to July 2013). DESIGN: A systematic review and Meta-study synthesis of
      qualitative studies that address perceived benefits and barriers to participation
      in CRC screening tests among adults 50 years of age or older. REVIEW METHODS: The
      two-staged Meta-study methodology by Paterson will be used to conduct this
      review. In stage 1, similarities/differences, patterns and themes will be
      identified across three levels of analysis while preserving the context of
      original studies. In stage 2, synthesis will extend beyond the analysis to
      generate new theory of the phenomenon through a process called Meta-synthesis.
      DISCUSSION: This review offers to generate a framework to better understand
      benefits and barriers that affect decision-making to participate in CRC screening
      among different sectors of the population. This framework will be a relevant tool
      for policy makers in framing educational materials, for patient-centered
      communication, and for researchers interested in the science of equity. This
      review is registered in PROSPERO (registration number: CRD42013005025).

PMID- 24578547
TI  - Reply: Hereditary myopathy with early respiratory failure is caused by mutations
      in the titin FN3 119 domain.

PMID- 24578545
TI  - Selective serotonin reuptake inhibition modulates response inhibition in
      Parkinson's disease.
AB  - Impulsivity is common in Parkinson's disease even in the absence of impulse
      control disorders. It is likely to be multifactorial, including a dopaminergic
      'overdose' and structural changes in the frontostriatal circuits for motor
      control. In addition, we proposed that changes in serotonergic projections to the
      forebrain also contribute to response inhibition in Parkinson's disease, based on
      preclinical animal and human studies. We therefore examined whether the selective
      serotonin reuptake inhibitor citalopram improves response inhibition, in terms of
      both behaviour and the efficiency of underlying neural mechanisms. This
      multimodal magnetic resonance imaging study used a double-blind randomized
      placebo-controlled crossover design with an integrated Stop-Signal and NoGo
      paradigm. Twenty-one patients with idiopathic Parkinson's disease (46-76 years
      old, 11 male, Hoehn and Yahr stage 1.5-3) received 30 mg citalopram or placebo in
      addition to their usual dopaminergic medication in two separate sessions. Twenty
      matched healthy control subjects (54-74 years old, 12 male) were tested without
      medication. The effects of disease and drug on behavioural performance and
      regional brain activity were analysed using general linear models. In addition,
      anatomical connectivity was examined using diffusion tensor imaging and tract
      based spatial statistics. We confirmed that Parkinson's disease caused impairment
      in response inhibition, with longer Stop-Signal Reaction Time and more NoGo
      errors under placebo compared with controls, without affecting Go reaction times.
      This was associated with less stop-specific activation in the right inferior
      frontal cortex, but no significant difference in NoGo-related activation.
      Although there was no beneficial main effect of citalopram, it reduced Stop
      Signal Reaction Time and NoGo errors, and enhanced inferior frontal activation,
      in patients with relatively more severe disease (higher Unified Parkinson's
      Disease Rating Scale motor score). The behavioural effect correlated with the
      citalopram-induced enhancement of prefrontal activation and the strength of
      preserved structural connectivity between the frontal and striatal regions. In
      conclusion, the behavioural effect of citalopram on response inhibition depends
      on individual differences in prefrontal cortical activation and frontostriatal
      connectivity. The correlation between disease severity and the effect of
      citalopram on response inhibition may be due to the progressive loss of forebrain
      serotonergic projections. These results contribute to a broader understanding of
      the critical roles of serotonin in regulating cognitive and behavioural control,
      as well as new strategies for patient stratification in clinical trials of
      serotonergic treatments in Parkinson's disease. 

PMID- 24578546
TI  - Regeneration of diabetic axons is enhanced by selective knockdown of the PTEN
      gene.
AB  - Diabetes mellitus renders both widespread and localized irreversible damage to
      peripheral axons while imposing critical limitations on their ability to
      regenerate. A major failure of regenerative capacity thereby imposes a 'double
      hit' in diabetic patients who frequently develop focal neuropathies such as
      carpal tunnel syndrome in addition to generalized diffuse polyneuropathy. The
      mechanisms of diabetic neuron regenerative failure have been speculative and few
      approaches have offered therapeutic opportunities. In this work we identify an
      unexpected but major role for PTEN upregulation in diabetic peripheral neurons in
      attenuating axon regrowth. In chronic diabetic neuropathy models in mice, we
      identified significant PTEN upregulation in peripheral sensory neurons of
      messenger RNA and protein compared to littermate controls. In vitro, sensory
      neurons from these mice responded to PTEN knockdown with substantial rises in
      neurite outgrowth and branching. To test regenerative plasticity in a chronic
      diabetic model with established neuropathy, we superimposed an additional focal
      sciatic nerve crush injury and assessed morphological, electrophysiological and
      behavioural recovery. Knockdown of PTEN in dorsal root ganglia ipsilateral to the
      side of injury was achieved using a unique form of non-viral short interfering
      RNA delivery to the ipsilateral nerve injury site and paw. In comparison with
      scrambled sequence control short interfering RNA, PTEN short interfering RNA
      improved several facets of regeneration: recovery of compound muscle action
      potentials, reflecting numbers of reconnected motor axons to endplates,
      conduction velocities of both motor and sensory axons, reflecting their
      maturation during regrowth, numbers and calibre of regenerating myelinated axons
      distal to the injury site, reinnervation of the skin by unmyelinated epidermal
      axons and recovery of mechanical sensation. Collectively, these findings identify
      a novel therapeutic approach, potentially applicable to other neurological
      conditions requiring specific forms of molecular knockdown, and also identify a
      unique target, PTEN, to treat diabetic neuroregenerative failure. 

PMID- 24578548
TI  - Episodic ataxia type 1: clinical characterization, quality of life and genotype
      phenotype correlation.
AB  - Episodic ataxia type 1 is considered a rare neuronal ion channel disorder
      characterized by brief attacks of unsteadiness and dizziness with persistent
      myokymia. To characterize the natural history, develop outcome measures for
      future clinical trials, and correlate genotype with phenotype, we undertook an
      international, prospective, cross-sectional study. Thirty-nine individuals (51%
      male) were enrolled: median age 37 years (range 15-65 years). We identified 10
      different pathogenic point mutations in KCNA1 that accounted for the genetic
      basis of 85% of the cohort. Participants with KCNA1 mutations were more likely to
      have a positive family history. Analysis of the total cohort showed that the
      first episode of ataxia occurred before age 20 in all but one patient, with an
      average age of onset of 7.9 years. Physical exertion, emotional stress and
      environmental temperature were the most common triggers for attacks. Attack
      frequency ranged from daily to monthly, even with the same KCNA1 genotype.
      Average attack duration was in the order of minutes. Ten participants (26%)
      developed permanent cerebellar signs, which were related to disease duration. The
      average Scale for the Assessment and Rating of Ataxia score (SARA, a standardized
      measure of cerebellar dysfunction on clinical examination, scores range from 0
      40) was an average of 3.15 for all participants (range 0-14), but was only 2 in
      those with isolated episodic ataxia compared with 7.7 in those with progressive
      cerebellar ataxia in addition to episodic ataxia. Thirty-seven participants
      completed the SF-36, a quality of life survey; all eight domain norm-based
      average scores (mean=50) were below normal with mental health being the lowest
      (41.3) in those with mutation positive episodic ataxia type 1. Scores on SF-36
      correlated negatively with attack frequency. Of the 39 participants in the study,
      33 harboured mutations in KCNA1 whereas the remaining six had no mutation
      identified. Episodic ataxia type 1 phenocopies have not been described previously
      and we report their clinical features, which appear to be different to those with
      a KCNA1 mutation. This large prospective study of both genetically confirmed
      episodic ataxia type 1 and episodic ataxia type 1 phenocopies provides detailed
      baseline characteristics of these disorders and their impact on participants. We
      found that attacks had a significant effect on quality of life. Unlike previous
      studies, we found that a significant number of individuals with genetically
      confirmed episodic ataxia type 1 (21%) had accumulated persistent cerebellar
      symptoms and signs. These data will enable the development of outcome measures
      for clinical trials of treatment.

PMID- 24578550
TI  - Festival lessons.

PMID- 24578555
TI  - Science and politics. Science misused to justify Ugandan antigay law.

PMID- 24578556
TI  - Energy. New review slams fusion project's management.

PMID- 24578557
TI  - Social science. Twitter offers entire data pool, but some wary of diving in.

PMID- 24578558
TI  - Europe. E.U. privacy protection bill would hamper research, scientists warn.

PMID- 24578559
TI  - Atmospheric evolution. New look at ancient mineral could scrap a test for early
      oxygen.

PMID- 24578560
TI  - Welcome to Beringia.

PMID- 24578549
TI  - Cerebral malaria in children: using the retina to study the brain.
AB  - Cerebral malaria is a dangerous complication of Plasmodium falciparum infection,
      which takes a devastating toll on children in sub-Saharan Africa. Although
      autopsy studies have improved understanding of cerebral malaria pathology in
      fatal cases, information about in vivo neurovascular pathogenesis is scarce
      because brain tissue is inaccessible in life. Surrogate markers may provide
      insight into pathogenesis and thereby facilitate clinical studies with the
      ultimate aim of improving the treatment and prognosis of cerebral malaria. The
      retina is an attractive source of potential surrogate markers for paediatric
      cerebral malaria because, in this condition, the retina seems to sustain
      microvascular damage similar to that of the brain. In paediatric cerebral malaria
      a combination of retinal signs correlates, in fatal cases, with the severity of
      brain pathology, and has diagnostic and prognostic significance. Unlike the
      brain, the retina is accessible to high-resolution, non-invasive imaging. We
      aimed to determine the extent to which paediatric malarial retinopathy reflects
      cerebrovascular damage by reviewing the literature to compare retinal and
      cerebral manifestations of retinopathy-positive paediatric cerebral malaria. We
      then compared retina and brain in terms of anatomical and physiological features
      that could help to account for similarities and differences in vascular
      pathology. These comparisons address the question of whether it is biologically
      plausible to draw conclusions about unseen cerebral vascular pathogenesis from
      the visible retinal vasculature in retinopathy-positive paediatric cerebral
      malaria. Our work addresses an important cause of death and neurodisability in
      sub-Saharan Africa. We critically appraise evidence for associations between
      retina and brain neurovasculature in health and disease, and in the process we
      develop new hypotheses about why these vascular beds are susceptible to
      sequestration of parasitized erythrocytes. 

PMID- 24578562
TI  - Raw data: access to inaccuracy.

PMID- 24578561
TI  - Can Down syndrome be treated?

PMID- 24578563
TI  - Raw data: research and health care goals differ.

PMID- 24578564
TI  - Raw data: access to inaccuracy--response.

PMID- 24578566
TI  - Intellectual property. A better route to tech standards.

PMID- 24578567
TI  - Ecology. Meet the new boss, same as the old boss.

PMID- 24578568
TI  - Materials science. The surface mobility of glasses.

PMID- 24578569
TI  - Climate change. The tropical Pacific Ocean--back in the driver's seat?

PMID- 24578570
TI  - Neuroscience. The neural code that makes us human.

PMID- 24578571
TI  - Anthropology. Out of Beringia?

PMID- 24578572
TI  - Materials science. How shape affects microtubule and nanoparticle assembly.

PMID- 24578573
TI  - Cell biology. Signaling shifts in allergy responses.

PMID- 24578574
TI  - A direct quantitative measure of surface mobility in a glassy polymer.
AB  - Thin polymer films have striking dynamical properties that differ from their bulk
      counterparts. With the simple geometry of a stepped polymer film on a substrate,
      we probe mobility above and below the glass transition temperature Tg. Above Tg
      the entire film flows, whereas below Tg only the near-surface region responds to
      the excess interfacial energy. An analytical thin-film model for flow limited to
      the free surface region shows excellent agreement with sub-Tg data. The system
      transitions from whole-film flow to surface localized flow over a narrow
      temperature region near the bulk Tg. The experiments and model provide a measure
      of surface mobility in a simple geometry where confinement and substrate effects
      are negligible. This fine control of the glassy rheology is of key interest to
      nanolithography among numerous other applications. 

PMID- 24578575
TI  - Promoter-bound trinucleotide repeat mRNA drives epigenetic silencing in fragile X
      syndrome.
AB  - Epigenetic gene silencing is seen in several repeat-expansion diseases. In
      fragile X syndrome, the most common genetic form of mental retardation, a CGG
      trinucleotide-repeat expansion adjacent to the fragile X mental retardation 1
      (FMR1) gene promoter results in its epigenetic silencing. Here, we show that FMR1
      silencing is mediated by the FMR1 mRNA. The FMR1 mRNA contains the transcribed
      CGG-repeat tract as part of the 5' untranslated region, which hybridizes to the
      complementary CGG-repeat portion of the FMR1 gene to form an RNA.DNA duplex.
      Disrupting the interaction of the mRNA with the CGG-repeat portion of the FMR1
      gene prevents promoter silencing. Thus, our data link trinucleotide-repeat
      expansion to a form of RNA-directed gene silencing mediated by direct
      interactions of the trinucleotide-repeat RNA and DNA. 

PMID- 24578576
TI  - Detection of a recurrent DNAJB1-PRKACA chimeric transcript in fibrolamellar
      hepatocellular carcinoma.
AB  - Fibrolamellar hepatocellular carcinoma (FL-HCC) is a rare liver tumor affecting
      adolescents and young adults with no history of primary liver disease or
      cirrhosis. We identified a chimeric transcript that is expressed in FL-HCC but
      not in adjacent normal liver and that arises as the result of a ~400-kilobase
      deletion on chromosome 19. The chimeric RNA is predicted to code for a protein
      containing the amino-terminal domain of DNAJB1, a homolog of the molecular
      chaperone DNAJ, fused in frame with PRKACA, the catalytic domain of protein
      kinase A. Immunoprecipitation and Western blot analyses confirmed that the
      chimeric protein is expressed in tumor tissue, and a cell culture assay indicated
      that it retains kinase activity. Evidence supporting the presence of the DNAJB1
      PRKACA chimeric transcript in 100% of the FL-HCCs examined (15/15) suggests that
      this genetic alteration contributes to tumor pathogenesis. 

PMID- 24578577
TI  - Cell surface ABP1-TMK auxin-sensing complex activates ROP GTPase signaling.
AB  - Auxin-binding protein 1 (ABP1) was discovered nearly 40 years ago and was shown
      to be essential for plant development and morphogenesis, but its mode of action
      remains unclear. Here, we report that the plasma membrane-localized transmembrane
      kinase (TMK) receptor-like kinases interact with ABP1 and transduce auxin signal
      to activate plasma membrane-associated ROPs [Rho-like guanosine triphosphatases
      (GTPase) from plants], leading to changes in the cytoskeleton and the shape of
      leaf pavement cells in Arabidopsis. The interaction between ABP1 and TMK at the
      cell surface is induced by auxin and requires ABP1 sensing of auxin. These
      findings show that TMK proteins and ABP1 form a cell surface auxin perception
      complex that activates ROP signaling pathways, regulating nontranscriptional
      cytoplasmic responses and associated fundamental processes. 

PMID- 24578579
TI  - Teen dating violence perpetration and relation to STI and sexual risk behaviours
      among adolescent males.
AB  - OBJECTIVES: To investigate teen dating violence (TDV) perpetration (physical,
      sexual or psychological violence) and association with STI and related sexual
      risk behaviours among urban male adolescents. METHODS: Adolescent male survey
      participants (N=134) were aged 14-20 years, recruited from urban health centres.
      Using crude and adjusted logistic regression, TDV perpetration was examined in
      relation to self-reported: STI, having sex with another person when they were
      only supposed to have sex with their main partner, and consistent condom use.
      RESULTS: Over one-third of males (45%) reported any TDV; 42% reported sexual
      violence perpetration, 13% reported perpetrating physical violence against a
      dating/sexual partner and 11% reported psychological violence, including threats
      of physical or sexual violence. Approximately 15% of males reported having ever
      had an STI, one quarter reported having sex with another person when they were
      only supposed to have sex with their main partner and 36% reported consistent
      condom use (past 3 months). In adjusted logistic regression models, TDV
      perpetration was significantly associated with self-reports of an STI (OR=3.3;
      95% CI 1.2 to 9.2) and having sex with another person when they were supposed to
      be only having sex with their main partner (OR=4.8; 95% CI 2.0 to 11.4). There
      was no significant association between TDV perpetration and consistent condom
      use. CONCLUSIONS: Current study findings are the first within the literature on
      adolescents to suggest that greater STI and sexual risk behaviours among male
      adolescents perpetrating TDV may be one mechanism explaining increased STI among
      female adolescents reporting TDV victimisation.

PMID- 24578578
TI  - Solar synthesis: prospects in visible light photocatalysis.
AB  - Chemists have long aspired to synthesize molecules the way that plants do-using
      sunlight to facilitate the construction of complex molecular architectures.
      Nevertheless, the use of visible light in photochemical synthesis is
      fundamentally challenging because organic molecules tend not to interact with the
      wavelengths of visible light that are most strongly emitted in the solar
      spectrum. Recent research has begun to leverage the ability of visible light
      absorbing transition metal complexes to catalyze a broad range of synthetically
      valuable reactions. In this review, we highlight how an understanding of the
      mechanisms of photocatalytic activation available to these transition metal
      complexes, and of the general reactivity patterns of the intermediates accessible
      via visible light photocatalysis, has accelerated the development of this diverse
      suite of reactions. 

PMID- 24578581
TI  - Intensive Reading Remediation in Grade 2 or 3: Are There Effects a Decade Later?
AB  - Despite data supporting the benefits of early reading interventions, there has
      been little evaluation of the long-term educational impact of these
      interventions, with most follow-up studies lasting less than two years (Suggate,
      2010). This study evaluated reading outcomes more than a decade after the
      completion of an 8-month reading intervention using a randomized design with
      second and third graders selected on the basis of poor word-level skills
      (Blachman et al., 2004). Fifty-eight (84%) of the original 69 participants took
      part in the study. The treatment group demonstrated a moderate to small effect
      size advantage on reading and spelling measures over the comparison group. There
      were statistically significant differences with moderate effect sizes between
      treatment and comparison groups on standardized measures of word recognition
      (i.e., Woodcock Basic Skills Cluster, d = 0.53; Woodcock Word Identification, d =
      0.62), the primary, but not exclusive, focus of the intervention. Statistical
      tests on other reading and spelling measures did not reach thresholds for
      statistical significance. Patterns in the data related to other educational
      outcomes, such as high school completion, favored the treatment participants,
      although differences were not significant.

PMID- 24578582
TI  - A multiscale MD-FE model of diffusion in composite media with internal surface
      interaction based on numerical homogenization procedure.
AB  - Mass transport by diffusion within composite materials may depend not only on
      internal microstructural geometry, but also on the chemical interactions between
      the transported substance and the material of the microstructure.
      Retrospectively, there is a gap in methods and theory to connect material
      microstructure properties with macroscale continuum diffusion characteristics.
      Here we present a new hierarchical multiscale model for diffusion within
      composite materials that couples material microstructural geometry and
      interactions between diffusing particles and the material matrix. This model,
      which bridges molecular dynamics (MD) and the finite element (FE) method, is
      employed to construct a continuum diffusion model based on a novel numerical
      homogenization procedure. The procedure is general and robust for evaluating
      constitutive material parameters of the continuum model. These parameters include
      the traditional bulk diffusion coefficients and, additionally, the distances from
      the solid surface accounting for surface interaction effects. We implemented our
      models to glucose diffusion through the following two geometrical/material
      configurations: tightly packed silica nanospheres, and a complex fibrous
      structure surrounding nanospheres. Then, rhodamine 6G diffusion analysis through
      an aga-rose gel network was performed, followed by a model validation using our
      experimental results. The microstructural model, numerical homogenization and
      continuum model offer a new platform for modeling and predicting mass diffusion
      through complex biological environment and within composite materials that are
      used in a wide range of applications, like drug delivery and nanoporous
      catalysts.

PMID- 24578583
TI  - Enumerating Microorganism Surrogates for Groundwater Transport Studies Using
      Solid-Phase Cytometry.
AB  - Investigations on the pollution of groundwater with pathogenic microorganisms,
      e.g. tracer studies for groundwater transport, are constrained by their potential
      health risk. Thus, microspheres are often used in groundwater transport studies
      as non-hazardous surrogates for pathogenic microorganisms. Even though pathogenic
      microorganisms occur at low concentrations in groundwater, current detection
      methods of microspheres (spectrofluorimetry, flow cytometry and epifluorescence
      microscopy) have rather high detection limits and are unable to detect rare
      events. Solid-phase cytometry (SPC) offers the unique capability of reliably
      quantifying extremely low concentrations of fluorescently labelled microorganisms
      or microspheres in natural waters, including groundwater. Until now, microspheres
      have been used in combination with SPC only for instrument calibration purposes
      and not for environmental applications. In this study, we explored the limits of
      the SPC methodology for its applicability to groundwater transport studies. The
      SPC approach proved to be a highly sensitive and reliable enumeration system for
      microorganism surrogates down to a minimum size of 0.5 MUm, in up to 500 ml of
      groundwater, and 0.75 MUm, in up to 1 ml of turbid surface water. Hence, SPC is
      proposed to be a useful method for enumerating microspheres for groundwater
      transport studies in the laboratory, as well as in the field when non-toxic,
      natural products are used.

PMID- 24578584
TI  - Biodiesel Co-Product (BCP) Decreases Soil Nitrogen (N) Losses to Groundwater.
AB  - This study compares a traditional agricultural approach to minimise N pollution
      of groundwater (incorporation of crop residues) with applications of small
      amounts of biodiesel co-product (BCP) to arable soils. Loss of N from soil to the
      aqueous phase was shown to be greatly reduced in the laboratory, mainly by
      decreasing concentrations of dissolved nitrate-N. Increases in soil microbial
      biomass occurred within 4 days of BCP application-indicating rapid adaptation of
      the soil microbial community. Increases in biomass-N suggest that microbes were
      partly mechanistic in the immobilisation of N in soil. Straw, meadow-grass and
      BCP were subsequently incorporated into experimental soil mesocosms of depth
      equal to plough layer (23 cm), and placed in an exposed netted tunnel to simulate
      field conditions. Leachate was collected after rainfall between the autumn of
      2009 and spring of 2010. Treatment with BCP resulted in less total-N transferred
      from soil to water over the entire period, with 32.1, 18.9, 13.2 and 4.2 mg N kg
      1 soil leached cumulatively from the control, grass, straw and BCP treatments,
      respectively. More than 99 % of nitrate leaching was prevented using BCP.
      Accordingly, soils provided with crop residues or BCP showed statistically
      significant increases in soil N and C compared to the control (no incorporation).
      Microbial biomass, indicated by soil ATP concentration, was also highest for
      soils given BCP (p < 0.05). These results indicate that field-scale incorporation
      of BCP may be an effective method to reduce nitrogen loss from agricultural
      soils, prevent nitrate pollution of groundwater and augment the soil microbial
      biomass.

PMID- 24578585
TI  - Decolourisation of Different Dyes by two Pseudomonas Strains Under Various Growth
      Conditions.
AB  - The aim of the present study was the decolourisation of mixture of two dyes
      belonging to different groups by two Pseudomonas fluorescens strains (Sz6 and
      SDz3). Influence of different incubation conditions on decolourisation
      effectiveness was evaluated. Dyes used in the experiment were diazo Evans blue
      (EB) and triphenylmethane brilliant green (BG). Another goal of the experiment
      was the estimation of toxicity of process by-products. Incubation conditions had
      a significant influence on the rate of decolourisation. The best results were
      reached in shaken and semistatic samples (exception Evans blue). After 24 h of
      experiment in semistatic conditions, BG removal reached up to 95.4 %, EB 72.8 %
      and dyes mixture 88.9 %. After 120 h, all tested dyes were completely removed. In
      most cases, dyes were removed faster and better by strain Sz6 than SDz3. At the
      end of the experiment, in majority of the samples, decrease of phyto- and
      zootoxicity was observed.

PMID- 24578586
TI  - Nitrogen Deposition Effects on Diatom Communities in Lakes from Three National
      Parks in Washington State.
AB  - The goal of this study was to document if lakes in National Parks in Washington
      have exceeded critical levels of nitrogen (N) deposition, as observed in other
      Western States. We measured atmospheric N deposition, lake water quality, and
      sediment diatoms at our study lakes. Water chemistry showed that our study lakes
      were ultra-oligotrophic with ammonia and nitrate concentrations often at or below
      detection limits with low specific conductance (<100 MUS/cm), and acid
      neutralizing capacities (<400 MUeq/L). Rates of summer bulk inorganic N
      deposition at all our sites ranged from 0.6 to 2.4 kg N ha-1 year-1 and were
      variable both within and across the parks. Diatom assemblages in a single
      sediment core from Hoh Lake (Olympic National Park) displayed a shift to
      increased relative abundances of Asterionella formosa and Fragilaria tenera
      beginning in the 1969-1975 timeframe, whereas these species were not found at the
      remaining (nine) sites. These diatom species are known to be indicative of N
      enrichment and were used to determine an empirical critical load of N deposition,
      or threshold level, where changes in diatom communities were observed at Hoh
      Lake. However, N deposition at the remaining nine lakes does not seem to exceed a
      critical load at this time. At Milk Lake, also in Olympic National Park, there
      was some evidence that climate change might be altering diatom communities, but
      more research is needed to confirm this. We used modeled precipitation for Hoh
      Lake and annual inorganic N concentrations from a nearby National Atmospheric
      Deposition Program station, to calculate elevation-corrected N deposition for
      1980-2009 at Hoh Lake. An exponential fit to this data was hindcasted to the 1969
      1975 time period, and we estimate a critical load of 1.0 to 1.2 kg N ha-1 year-1
      for wet deposition for this lake.

PMID- 24578588
TI  - Generational Patterns in Mexican Americans' Academic Performance in an
      Unwelcoming Political Context.
AB  - Research has shown that immigrant students often do better academically than
      their U.S.-born peers from the same ethnic group but it is unclear whether this
      pattern holds for Mexican Americans. We examined the academic performance of four
      generations of Mexican American students from fifth to 10th grade looking for
      generation differences and explanations for them. Using data from 749 families,
      we tested a model with fifth grade variables that differed by generation as
      potential mediators linking student generation to 10th grade academic
      performance. Results showed that immigrants were academically behind at fifth
      grade but caught up by seventh. Only economic hardship mediated the long term
      relationship between student generation and 10th grade academic performance;
      maternal educational expectations and child language hassles, English usage,
      discrimination, and mainstream values helped explained the early academic deficit
      of immigrant children. The results identified potential targets for interventions
      to improve Mexican American students' academic performance.

PMID- 24578587
TI  - Social Selection and Indirect Genetic Effects in Structured populations.
AB  - Social selection and indirect genetic effects (IGEs) are established concepts in
      both behavioural ecology and evolutionary genetics. While IGEs describe effects
      of an individual's genotype on phenotypes of social partners (and may thus affect
      their fitness indirectly), the concept of social selection assumes that a given
      phenotype in one individual affects the fitness of other individuals directly.
      Although different frameworks, both have been used to investigate the evolution
      of social traits, such as cooperative behaviour. Despite their similarities (both
      concepts consider interactions among individuals), they differ in the type of
      interaction. It remains unclear whether the two concepts make the same
      predictions about evolutionary trajectories or not. To address this question, we
      investigate four possible scenarios of social interactions and compare the
      effects of IGEs and social selection for trait evolution in a multi-trait multi
      member model. We show that the two mechanisms can yield similar evolutionary
      outcomes and that both can create selection pressure at the group level. However,
      the effect of IGEs can be stronger due to the possibility of feedback loops.
      Finally, we demonstrate that IGEs, but not social selection gradients, may lead
      to differences in the direction of evolutionary response between genotypes and
      phenotypes.

PMID- 24578589
TI  - Integrative Analysis of Cancer Diagnosis Studies with Composite Penalization.
AB  - In cancer diagnosis studies, high-throughput gene profiling has been extensively
      conducted, searching for genes whose expressions may serve as markers. Data
      generated from such studies have the "large d, small n" feature, with the number
      of genes profiled much larger than the sample size. Penalization has been
      extensively adopted for simultaneous estimation and marker selection. Because of
      small sample sizes, markers identified from the analysis of single datasets can
      be unsatisfactory. A cost-effective remedy is to conduct integrative analysis of
      multiple heterogeneous datasets. In this article, we investigate composite
      penalization methods for estimation and marker selection in integrative analysis.
      The proposed methods use the minimax concave penalty (MCP) as the outer penalty.
      Under the homogeneity model, the ridge penalty is adopted as the inner penalty.
      Under the heterogeneity model, the Lasso penalty and MCP are adopted as the inner
      penalty. Effective computational algorithms based on coordinate descent are
      developed. Numerical studies, including simulation and analysis of practical
      cancer datasets, show satisfactory performance of the proposed methods.

PMID- 24578590
TI  - Comparative Assessment of Gasification Based Coal Power Plants with Various CO2
      Capture Technologies Producing Electricity and Hydrogen.
AB  - Seven different types of gasification-based coal conversion processes for
      producing mainly electricity and in some cases hydrogen (H2), with and without
      carbon dioxide (CO2) capture, were compared on a consistent basis through
      simulation studies. The flowsheet for each process was developed in a chemical
      process simulation tool "Aspen Plus". The pressure swing adsorption (PSA),
      physical absorption (Selexol), and chemical looping combustion (CLC) technologies
      were separately analyzed for processes with CO2 capture. The performances of the
      above three capture technologies were compared with respect to energetic and
      exergetic efficiencies, and the level of CO2 emission. The effect of air
      separation unit (ASU) and gas turbine (GT) integration on the power output of all
      the CO2 capture cases is assessed. Sensitivity analysis was carried out for the
      CLC process (electricity-only case) to examine the effect of temperature and
      water-cooling of the air reactor on the overall efficiency of the process. The
      results show that, when only electricity production in considered, the case using
      CLC technology has an electrical efficiency 1.3% and 2.3% higher than the PSA and
      Selexol based cases, respectively. The CLC based process achieves an overall CO2
      capture efficiency of 99.9% in contrast to 89.9% for PSA and 93.5% for Selexol
      based processes. The overall efficiency of the CLC case for combined electricity
      and H2 production is marginally higher (by 0.3%) than Selexol and lower (by 0.6%)
      than PSA cases. The integration between the ASU and GT units benefits all three
      technologies in terms of electrical efficiency. Furthermore, our results suggest
      that it is favorable to operate the air reactor of the CLC process at higher
      temperatures with excess air supply in order to achieve higher power efficiency.

PMID- 24578591
TI  - Exploring the Amount and Type of Writing Instruction during Language Arts
      Instruction in Kindergarten Classrooms.
AB  - The objective of this exploratory investigation was to examine the nature of
      writing instruction in kindergarten classrooms and to describe student writing
      outcomes at the end of the school year. Participants for this study included 21
      teachers and 238 kindergarten children from nine schools. Classroom teachers were
      videotaped once each in the fall and winter during the 90 minute instructional
      block for reading and language arts to examine time allocation and the types of
      writing instructional practices taking place in the kindergarten classrooms.
      Classroom observation of writing was divided into student-practice variables
      (activities in which students were observed practicing writing or writing
      independently) and teacher-instruction variables (activities in which the teacher
      was observed providing direct writing instruction). In addition, participants
      completed handwriting fluency, spelling, and writing tasks. Large variability was
      observed in the amount of writing instruction occurring in the classroom, the
      amount of time kindergarten teachers spent on writing and in the amount of time
      students spent writing. Marked variability was also observed in classroom
      practices both within and across schools and this fact was reflected in the large
      variability noted in kindergartners' writing performance.

PMID- 24578592
TI  - Women's Preference of Therapist Based on Sex of Therapist and Presenting Problem:
      An Analogue Study.
AB  - An analogue study was conducted to examine differences in women's preference for
      and anticipated comfort self-disclosing to hypothetical therapists of different
      sexes based on the type of hypothetical presenting problem. The impact of general
      level of self-disclosure was also examined. Participants included female college
      students (n=187). Anticipated comfort self-disclosing to male or female therapist
      was rated by subjects when presented with therapists of each sex with the same
      qualifications. Women preferred and reported higher levels of anticipated comfort
      self-disclosing to a female therapist. Type of hypothetical presenting problem
      and general level of self-disclosure also impacted anticipated comfort self
      disclosing. There was an interaction between general level self-disclosure and
      the sex of therapist on anticipated comfort self-disclosing. General level of
      self-disclosure only impacted anticipated comfort self-disclosing when the
      therapist was male. This information is relevant for therapists or organizations
      that provide psycho-social services to women. Organizations may want to inquire
      about a client's preferences about sex of therapist beforehand and, if possible,
      cater to the client's preference.

PMID- 24578593
TI  - Functional analysis of TaABF1 during abscisic acid and gibberellin signalling in
      aleurone cells of cereal grains.
AB  - The wheat transcription factor TaABF1 physically interacts with the protein
      kinase PKABA1 and mediates both abscisic acid (ABA)-induced and ABA-suppressed
      gene expression. In bombarded aleurone cells of imbibing grains, the effect of
      TaABF1 in down-regulating the gibberellin (GA)-induced Amy32b promoter was
      stronger in the presence of exogenous ABA. As these grains contained low levels
      of endogenous ABA, the effect of TaABF1 may also be mediated by ABA-induced
      activation even in the absence of exogenous ABA. Levels of TaABF1 protein
      decreased slightly during imbibition of afterripened grains. However, TaABF1
      levels (especially in aleurone layers) were not substantially affected by
      exogenous ABA or GA, indicating that changes in TaABF1 protein level are not an
      important part of regulating its role in hormone signalling. We found that TaABF1
      was phosphorylated in vivo in aleurone cells, suggesting a role for post
      translational modification in regulating TaABF1 activity. Induction of Amy32b by
      overexpression of the transcription factor GAMyb could not be prevented by
      TaABF1, indicating that TaABF1 acts upstream of GAMyb transcription in the
      signalling pathway. Supporting this view, knockdown of TaABF1 by RNA interference
      resulted in increased expression from the GAMyb promoter. These results are
      consistent with a model in which TaABF1 is constitutively present in aleurone
      cells, while its ability to down-regulate GAMyb is regulated in response to ABA.

PMID- 24578594
TI  - Correlation between transient ischemic dilatation (TID) and coronary artery
      disease in Saudi male patients.
AB  - OBJECTIVE: A high transient ischemic dilatation ratio (TID) for the left
      ventricle (LV) from a gated myocardial perfusion imaging (G-MPI) study is widely
      believed to be associated with significant coronary artery disease (CAD). We have
      investigated the relationship between TID and CAD for our male Saudi Arabian
      patient population. METHODS: In this retrospective study, all male Saudi Arabian
      patients who underwent a two-day G-MPI study using Tc99m MIBI during the year
      2011 having a TID ? 1.20 were included. Quantitative perfusion and gated
      parameters were obtained using Cedar Sinai's AutoQuant software version 3.0,
      2003, Means of summed stress scores, summed rest scores and summed difference
      scores (SSS, SRS, SDS, respectively), stress and rest ejection fraction (EF) were
      calculated. Visual interpretation was performed to classify the perfusion as
      normal, fixed, mixed (fixed and reversible defects), single reversible or
      multiple reversible defects. Coronary angiograms were assessed as normal with no
      CAD, single vessel, two-vessel or three-vessel disease. Correlations between the
      TID and other parameters were studied using analysis of variance (ANOVA) with IBM
      SPSS version 20. RESULTS: A total of 52 male patients had a high TID of ?1.20
      (mean 1.30 +/- 0.13). Ten patients had a SSS of 0-3 and 16 were classified as
      normal by visual assessment. Stress EF (mean 50.4 +/- 12%) was lower than the
      rest EF (mean 56.6 +/- 12.8%) with the difference being statistically significant
      (Students paired t-test, p = 0.001). Angiography results were available in 44
      patients, 3 having a normal angiogram, 24 having three vessel disease, 7 having
      two vessel disease and 10 having one vessel disease. Five patients with normal
      perfusion and SSS = 0-3 had CAD as seen on a coronary angiography. CAD on
      coronary angiography showed a significant correlation with perfusion
      abnormalities as assessed by visual interpretation (p = 0.002). TID showed a
      significantly correlation with both perfusion abnormalities (p = 0.009), as
      assessed by visual interpretation, and with Summed difference scores, SDS (p =
      0.000). CONCLUSION: A high TID on G-MPI was a very sensitive indicator of
      significant CAD. In patients with normal perfusion and high TID further workup is
      warranted.

PMID- 24578596
TI  - Pre-ejection mitral annular motion velocity responses to dobutamine infusion: A
      quantitative approach for assessment of myocardial viability.
AB  - BACKGROUND: Dobutamine stress echocardiography (DSE) is widely used for detection
      of myocardial viability. The main limitation of DSE is its subjective
      interpretation. Assessment of mitral annular motion velocities with tissue
      Doppler imaging is a simple and quantitative measurement. OBJECTIVE: To determine
      the relationship between myocardial viability and regional systolic mitral
      annular motion tissue Doppler velocities responses to dobutamine stress. METHODS:
      Our study group included 42 patients with previous myocardial infarction referred
      for coronary angiography and revascularization. We did dobutamine stress tissue
      Doppler echocardiography (DSTDE) measuring velocities of pre-ejection wave (pre
      Ej) and peak ejection wave (Ej) at rest and during low-dose dobutamine infusion.
      We did follow up echocardiography after 1 month. RESULTS: After exclusion of the
      normokinetic walls, we analyzed 196 walls. Using receiver operator characteristic
      ROC curves, the optimal cut-off value for viability assessment was an increase of
      1.75 cm/s in pre-ejection velocity during DSTDE (area under the curve 0.70, p <
      0.001). On the other hand, the optimal cut-off value for viability assessment was
      an increase of 1.75 cm/s in ejection velocity during DSTDE (area under the curve
      0.613, p = 0.01). The sensitivity, specificity, and total accuracy of the DSTSE
      (pre-Ej) versus the gold standard for detection of myocardial viability were
      66.15%, 67.94%, and 67.35%, respectively. The sensitivity, specificity, and total
      accuracy of the DTSE (Ej) were 56.92%, 64.12%, and 61.43%, respectively. There
      was a good correlation between the pre-Ej at 5 ug/kg/min dobutamine infusion and
      the pre-Ej after revascularization (r = 0.64, p = 0.01) while the correlation
      with the Ej was moderate (r = 0.50, p = 0.01). CONCLUSION: Viable left
      ventricular myocardium could be identified easily and quantitatively with pre
      ejection mitral annular velocity during dobutamine infusion. The pre-ejection
      wave during DSTDE showed greater sensitivity and specificity for the prediction
      of myocardial viability than the ejection wave.

PMID- 24578595
TI  - Hypertrophic cardiomyopathy in the Saudi Arabian population: Clinical and
      echocardiographic characteristics and outcome analysis.
AB  - BACKGROUND: Current published literature on hypertrophic cardiomyopathy (HCM)
      comes primarily from Western populations. There is no published data on clinical
      and echocardiographic characteristics and long-term outcome of HCM in an Arab
      population. METHODS: We conducted a retrospective analysis of all patients 16
      years or older diagnosed with HCM at our institution. Detailed clinical and
      echocardiographic data were collected and outcome was analyzed. RESULTS: A total
      of 69 patients were identified as having HCM. The mean age was 42 +/- 16 years
      with 71% male patients. All patients were Saudi citizens with Arab ancestry.
      Details about family history and presenting symptoms were available for 44 and 48
      patients consecutively. Nine (18%) patients were asymptomatic and were diagnosed
      based on abnormal cardiac auscultation. The commonest presenting symptoms were
      dyspnea with or without chest pain and palpitations occurring in 40 (81%)
      patients. Only four (9%) of 44 patients had a family history of HCM and /or
      sudden cardiac death (SCD). The most common ECG abnormality was left ventricular
      hypertrophy (LVH) present in 60 (86%) patients. The commonest septal hypertrophy
      morphology was mid-septal (catenoid) in 30 (43%) followed by neutral in 23 (33%),
      basal septal (sigmoid) in 3 (4%) and apical in 6 (8%) patients. Twenty (28%)
      patients had evidence of resting left ventricular cavity gradient of ?30 mmHg.
      Eleven (16%) patients had evidence of biventricular hypertrophy. Left ventricular
      ejection fraction was normal in 65 (94%) patients. Over a median (25-75
      percentile) follow-up of 7 years (4.5-10), only three patients died, all of non
      cardiac causes. There were no cases of SCD during the follow-up period. Six
      patients required an implantable cardioverter-defibrillator (ICD); five for
      primary prevention and one for secondary prevention. Only one patient progressed
      to end stage dilated cardiomyopathy. CONCLUSION: The natural history of
      hypertrophic cardiomyopathy in the Saudi population appears to be benign with
      catenoid morphology being the most common septal hypertrophy pattern. Risk of SCD
      appears to be quite low in this population.

PMID- 24578597
TI  - Usefulness of the multiplanar reformatting mode of three-dimensional
      echocardiography in evaluating valvular and structural heart disease: An
      experience from Saudi Arabia.
AB  - OBJECTIVE: The aim of this study is to compare the feasibility and capacity of
      multiplanar reformatting (MPR) mode of three-dimensional echocardiography (3DE
      MPR technique) with two-dimensional echocardiography (2DE) for visualizing
      morphological details during evaluation of congenital heart disease (CHD). The
      study also seeks to validate the accuracy of 3DE MPR in determining cardiac
      valvular lesions and the application of the 3DE-MPR technique in daily clinical
      practice. METHODS: A cross-sectional study was carried out at Madinah Cardiac
      Centre, Saudi Arabia from May to December 2012. Various forms of CHD were
      diagnosed in 43 patients by conventional 2DE, and the patients were then examined
      with the 3DE-MPR technique using dedicated software and a standard protocol.
      RESULTS: Of the 43 patients, 23 (53.5%) were males and 20 (46.5%) females. Their
      age varied from 30 days to 146 months (mean age, 70.2 months and SD = 42.5
      months) and their weight from 4 to 42 kg (mean weight, 20.2 kg and SD = 9.7 kg).
      The 2DE showed left heart lesions in nine patients (20.9%), right heart lesions
      in 23 (53.5%), atrial septal defects in five (11.6%) and complex CHD in six
      patients (14%). The 3DE MPR technique application and analysis was possible in
      all patients. The study demonstrated the fields where 3DE MPR was of additive
      value to conventional 2DE for the vena contracta area in valvular regurgitation
      severity and the planimetry for the valvular stenosis precise estimation, enface
      views of atrial septal defects with direct visualisation of shape and size of the
      defect, and segmental analysis of complex CHD using one window. The clinician and
      surgeon were then able to determine the mechanism and severity of the lesions and
      thus decide on appropriate treatment and management. CONCLUSION: The study
      demonstrated the usefulness of 3DE-MPR as a complement to conventional 2DE. The
      technique is a significant technological breakthrough that allows instant
      visualization of morphological details and precise determination of cardiac
      valvular lesions, which were less clearly delineated by 2DE alone.

PMID- 24578598
TI  - Aortic valve replacement in children: Options and outcomes.
AB  - Several disease pathologies such as congenital heart disease and rheumatic fever
      can affect the aortic valve (AV) in children frequently necessitating
      intervention. While percutaneous or surgical AV repair is recommended as initial
      management strategy in children with AV disease, AV replacement (AVR) might
      become necessary in children with significant valve destruction and after repair
      or intervention failure. AVR in children is associated with distinct clinical and
      technical problems owing to several anatomic, social and prosthesis-related
      issues. In the current review, we list different AV substitutes, discuss their
      advantages and shortcomings, outline AVR results in children, and explore the
      divergence of outcomes in various age, anatomy and pathology subgroups; all in
      the aim to identify optimal AVR choice for each patient taking into consideration
      his unique anatomic and demographic characteristics. 

PMID- 24578600
TI  - Cardiac hydatid cyst revealed by ventricular tachycardia.
AB  - Hydatid disease is a human parasitic infestation caused by the larval stage of
      Echinococcus Granulosus. The liver and the lungs are the most common locations.
      Cardiac involvement is rare and accounts for 0.5-2% of all hydatid disease. We
      report an unusual presentation of cardiac hydatid cyst revealed by ventricular
      tachycardia in a patient with a history of cerebral hydatid cyst. 

PMID- 24578599
TI  - PCI in a case of dual (type IV) LAD with anomalous origin of the LCx from RCA.
AB  - Dual left anterior descending coronary artery (LAD) originating from the left
      main stem and the right coronary artery (type IV LAD) is a rare congenital
      anomaly. Its association with an anomalous origin of the left circumflex (LCx)
      from RCA is even rarer. We describe a patient presenting with acute inferior wall
      myocardial infarction, who was subsequently found to have this coronary anomaly.
      He underwent staged PCI of the dominant RCA and anomalous LCx successfully
      through the radial route. We conclude that anomalous coronaries can be safely and
      successfully treated through the radial route after careful evaluation of origin
      and course of the anomalous vessels. CT coronary angiography is extremely useful
      in delineating the vessel course and particularly their relation to great
      arteries. 

PMID- 24578601
TI  - Carcinoid heart disease and the utility of 3D trans-thoracic and trans-esophageal
      echocardiography: Two clinical cases.
AB  - Carcinoid tumors are rare neuroendocrine malignancies. We present two cases of
      metastatic carcinoid tumors, complicated by carcinoid syndrome and by cardiac
      valve involvement. Carcinoid syndrome is characterized by secretory diarrhea,
      episodic flushing, and bronchospasm. Cardiac involvement occurs in up to 50% of
      patients with metastatic carcinoid tumors which commonly causes abnormalities of
      the right sided valves. Echocardiography is the best available and non invasive
      technique for diagnosis. Characteristic features of carcinoid heart disease are
      thickened, shortened, retracted, and fixed or partially fixed valve leaflets.
      Three-dimensional (3D) echocardiography provided an en face view of pulmonary and
      tricuspid valve, not obtainable by two-dimensional echocardiography, and improved
      delineation of the relationship between these structures and cardiac chambers. 

PMID- 24578602
TI  - Advantages of 18F-fluorodeoxyglucose positron emission tomography combined with
      computed tomography in detecting post cardiac surgery infections.
AB  - The 18F-fluorodeoxyglucose positron emission tomography combined with computed
      tomography (FDG-PET/CT) offers an excellent negative predictive value.
      Consequently, it is a reliable tool for excluding an infectious phenomenon in
      case of negativity. In case of persistent fever of unknown origin after cardiac
      surgery and in combination with other bacteriological examinations and medical
      imaging, we can rely on FDG-PET/CT to confirm or eliminate deep infections and
      prosthetic endocarditis. For this reason, FDG-PET/CT should be considered among
      the examinations to be performed in case of suspected infection after cardiac
      surgery. We have reported the case of a 76-year-old man who presented with a
      fever of unknown origin and recurrent septic shocks after a biological Bentall
      procedure combined with left anterior descending (LAD) coronary artery
      revascularization by the left internal thoracic artery. We performed a FDG-PET/CT
      which showed external iliac vein and right common femoral vein hyperfixation with
      infiltration of adjacent soft tissues, highly suspected to be an infectious
      process. LEARNING OBJECTIVE: The aim of this case report is to show that FDG
      PET/CT, in combination with other bacteriological examinations and medical
      imaging, can be extremely helpful in detecting deep infectious sources, even
      during the early postoperative period.

PMID- 24578604
TI  - A nomenclator of extant and fossil taxa of the Valvatidae (Gastropoda,
      Ectobranchia).
AB  - A compilation of all supra- and (infra-) specific taxa of extant and fossil
      Valvatidae, a group of freshwater operculate snails, is provided, including taxa
      initially described in this family and subsequently classified in other families,
      as well as names containing errors or misspellings. The extensive reference list
      is directly linked to the available electronic source (digital view or pdf
      download) of the respective papers. 

PMID- 24578603
TI  - Postpartal subclinical endometritis alters transcriptome profiles in liver and
      adipose tissue of dairy cows.
AB  - Transcriptome alterations in liver and adipose tissue of cows with subclinical
      endometritis (SCE) at 29 d postpartum were evaluated. Bioinformatics analysis was
      performed using the Dynamic Impact Approach by means of KEGG and DAVID databases.
      Milk production, blood metabolites (non-esterified fatty acids, magnesium), and
      disease biomarkers (albumin, aspartate aminotransferase) did not differ greatly
      between healthy and SCE cows. In liver tissue of cows with SCE, alterations in
      gene expression revealed an activation of complement and coagulation cascade,
      steroid hormone biosynthesis, apoptosis, inflammation, oxidative stress, MAPK
      signaling, and the formation of fibrinogen complex. Bioinformatics analysis also
      revealed an inhibition of vitamin B3 and B6 metabolism with SCE. In adipose, the
      most activated pathways by SCE were nicotinate and nicotinamide metabolism, long
      chain fatty acid transport, oxidative phosphorylation, inflammation, T cell and B
      cell receptor signaling, and mTOR signaling. Results indicate that SCE in dairy
      cattle during early lactation induces molecular alterations in liver and adipose
      tissue indicative of immune activation and cellular stress. 

PMID- 24578605
TI  - Spatial Variation in Particulate Matter Components over a Large Urban Area.
AB  - To characterize exposures to particulate matter (PM) and its components, we
      performed a large sampling study of small-scale spatial variation in size
      resolved particle mass and composition. PM was collected in size ranges of < 0.2,
      0.2-to-2.5, and 2.5-to-10 MUm on a scale of 100s to 1000s of meters to capture
      local sources. Within each of eight Southern California communities, up to 29
      locations were sampled for rotating, month-long integrated periods at two
      different times of the year, six months apart, from Nov 2008 through Dec 2009.
      Additional sampling was conducted at each community's regional monitoring station
      to provide temporal coverage over the sampling campaign duration. Residential
      sampling locations were selected based on a novel design stratified by high- and
      low-predicted traffic emissions and locations over- and under-predicted from
      previous dispersion model and sampling comparisons. Primary vehicle emissions
      constituents, such as elemental carbon (EC), showed much stronger patterns of
      association with traffic than pollutants with significant secondary formation,
      such as PM2.5 or water soluble organic carbon. Associations were also stronger
      during cooler times of the year (Oct through Mar). Primary pollutants also showed
      greater within-community spatial variation compared to pollutants with secondary
      formation contributions. For example, the average cool-season community mean and
      standard deviation (SD) for EC were 1.1 and 0.17 MUg/m3, respectively, giving a
      coefficient of variation (CV) of 18%. For PM2.5, average mean and SD were 14 and
      1.3 MUg/m3, respectively, with a CV of 9%. We conclude that within-community
      spatial differences are important for accurate exposure assessment of traffic
      related pollutants.

PMID- 24578606
TI  - STEM enrichment programs and graduate school matriculation: the role of science
      identity salience.
AB  - Improving the state of science education in the United States has become a
      national priority. One response to this problem has been the implementation of
      STEM enrichment programs designed to increase the number of students that enter
      graduate programs in science. Current research indicates enrichment programs have
      positive effects for student performance, degree completion, interest in science
      and graduate enrollment. Moreover, research suggests that beyond improving
      performance in STEM, and providing access to research experience and faculty
      mentoring, enrichment programs may also increase the degree to which students
      identify as scientists. However, researchers investigating the role of science
      identity on student outcomes have focused primarily on subjective outcomes,
      leaving a critical question of whether science identity also influences objective
      outcomes such as whether students attend graduate school. Using identity theory,
      this study addresses this issue by investigating science identity as a mechanism
      linking enrichment program participation to matriculation into graduate science
      programs. Quantitative results from a panel study of 694 students indicate that
      science identity salience, along with research experience and college GPA,
      mediate the effect of enrichment program participation on graduate school
      matriculation. Further, results indicate that although the social psychological
      process by which science identity salience develops operates independently from
      student GPA, science identity amplifies the effect of achievement on graduate
      school matriculation. These results indicate that policies seeking to increase
      the efficacy of enrichment programs and increase representation in STEM graduate
      programs should be sensitive to the social and academic aspects of STEM
      education.

PMID- 24578608
TI  - Genetic polymorphisms in SLC23A2 as predictive biomarkers of severe acute
      toxicities after treatment with a definitive 5-fluorouracil/cisplatin-based
      chemoradiotherapy in Japanese patients with esophageal squamous cell carcinoma.
AB  - OBJECTIVE: Definitive chemoradiotherapy (CRT) with 5-fluorouracil (5-FU) and
      cisplatin (CDDP) is one of the standard therapies for esophageal squamous cell
      carcinoma (ESCC); however, inter-individual variations in clinical outcomes have
      yet to be investigated. In the present study, single nucleotide polymorphisms
      (SNPs) in SLC23A2 gene were retrospectively evaluated in 49 Japanese patients
      with ESCC who were treated with a definitive 5-FU/CDDP-based CRT, and the
      predictive values for the clinical response, severe acute toxicities, and long
      term survival were assessed. METHODS: A course consisted of the continuous
      infusion of 5-FU at 400 mg/m(2)/day for days 1-5 and 8-12, the infusion of CDDP
      at 40 mg/m(2)/day on days 1 and 8, and radiation at 2 Gy/day on days 1 to 5, 8 to
      12, and 15 to 19, with a second course being repeated after a 2-week interval.
      The SLC23A2 SNPs rs2681116, rs13037458, rs1715364, rs4987219, and rs1110277 were
      evaluated. RESULTS: The rs2681116 and rs13037458 had a tendency to predict the
      clinical response (p=0.144 and 0.085, respectively) and long-term survival
      (p=0.142 and 0.056, respectively). The rs4987219 and rs1110277 correlated with
      severe acute leukopenia (p=0.025) and stomatitis (p=0.019), respectively.
      CONCLUSIONS: Further investigations with a larger number of patients or an in
      vitro study are needed to confirm the predictive values of genetic polymorphisms
      in SLC23A2.

PMID- 24578609
TI  - Antibacterial activity of a cardanol from Thai Apis mellifera propolis.
AB  - BACKGROUND: Propolis is a sticky, dark brown resinous residue made by bees that
      is derived from plant resins. It is used to construct and repair the nest, and in
      addition possesses several diverse bioactivities. Here, propolis from Apis
      mellifera from Nan province, Thailand, was tested for antibacterial activity
      against Gram(+ve) (Staphylococcus aureus and Paenibacillus larvae) and Gram(-ve)
      (Escherichia coli) bacteria. MATERIALS AND METHODS: The three bacterial isolates
      were confirmed for species designation by Gram staining and analysis of the
      partial sequence of 16S rDNA. Propolis was sequentially extracted by methanol,
      dichloromethane and hexane. The antibacterial activity was determined by agar
      well diffusion and microbroth dilution assays using streptomycin as a positive
      control. The most active crude extract was further purified by quick column and
      adsorption chromatography. The apparent purity of each bioactive fraction was
      tested by thin layer chromatography. The chemical structure of the isolated
      bioactive compound was analyzed by nuclear magnetic resonance (NMR). RESULTS:
      Crude methanol extract of propolis showed the best antibacterial activity with a
      minimum inhibition concentration (MIC) value of 5 mg/mL for S. aureus and E. coli
      and 6.25 mg/mL for P. larvae. After quick column chromatography, only three
      active fractions were inhibitory to the growth of S. aureus and E. coli with MIC
      values of 6.25 and 31.3 ug/mL, respectively. Further adsorption chromatography
      yielded one pure bioactive fraction (A1A) with an IC50 value of 0.175 ug/mL for
      E. coli and 0.683 ug/mL for P. larvae, and was determined to be cardanol by NMR
      analysis. Scanning and transmission electron microscopy analysis revealed unusual
      shaped (especially in dividing cells), damaged and dead cells in cardanol-treated
      E. coli. CONCLUSION: Thai propolis contains a promising antibacterial agent.

PMID- 24578607
TI  - Two-year follow-up results of fluoroscopic cervical epidural injections in
      chronic axial or discogenic neck pain: a randomized, double-blind, controlled
      trial.
AB  - STUDY DESIGN: A randomized, double-blind, active-controlled trial. OBJECTIVE: To
      assess the effectiveness of cervical interlaminar epidural injections of local
      anesthetic with or without steroids for the management of axial or discogenic
      pain in patients without disc herniation, radiculitis, or facet joint pain.
      SUMMARY OF BACKGROUND DATA: Cervical discogenic pain without disc herniation is a
      common cause of suffering and disability in the adult population. Once
      conservative management has failed and facet joint pain has been excluded,
      cervical epidural injections may be considered as a management tool. Despite a
      paucity of evidence, cervical epidural injections are one of the most commonly
      performed nonsurgical interventions in the management of chronic axial or disc
      related neck pain. METHODS: One hundred and twenty patients without disc
      herniation or radiculitis and negative for facet joint pain as determined by
      means of controlled diagnostic medial branch blocks were randomly assigned to one
      of the 2 treatment groups. Group I patients received cervical interlaminar
      epidural injections of local anesthetic (lidocaine 0.5%, 5 mL), whereas Group II
      patients received 0.5% lidocaine, 4 mL, mixed with 1 mL or 6 mg of nonparticulate
      betamethasone. The primary outcome measure was >= 50% improvement in pain and
      function. Outcome assessments included numeric rating scale (NRS), Neck
      Disability Index (NDI), opioid intake, employment, and changes in weight.
      RESULTS: Significant pain relief and functional improvement (>= 50%) was present
      at the end of 2 years in 73% of patients receiving local anesthetic only and 70%
      receiving local anesthetic with steroids. In the successful group of patients,
      however, defined as consistent relief with 2 initial injections of at least 3
      weeks, significant improvement was illustrated in 78% in the local anesthetic
      group and 75% in the local anesthetic with steroid group at the end of 2 years.
      The results reported at the one-year follow-up were sustained at the 2-year
      follow-up. CONCLUSIONS: Cervical interlaminar epidural injections with or without
      steroids may provide significant improvement in pain and functioning in patients
      with chronic discogenic or axial pain that is function-limiting and not related
      to facet joint pain.

PMID- 24578610
TI  - Ulinastatin preconditioning attenuates inflammatory reaction of hepatic ischemia
      reperfusion injury in rats via high mobility group box 1(HMGB1) inhibition.
AB  - Objective It has been found that ulinastatin (UTI) can attenuate hepatic injury
      in a rat model of ischemia reperfusion (IR), but the specific mechanism is
      unclear. This study aims to investigate possible pathomechanism of ulinastatin in
      reducing the inflammatory response after hepatic IR. Methods A male sprague
      dawley(SD) rat model of hepatic ischemia reperfusion injury was used. The rats
      were randomly divided into 4 groups on average, which were 0.9% saline and IR
      group as control, ulinastatin preconditioning (UPC) group, UPC+rHMGB1
      (recombinant HMGB1) group and UPC +anti-HMGB1 group. Serum aminotransferases, TNF
      alpha, IL-1 and Myeloperoxidase (MPO) levels were measured. Histopathology
      examination and apoptotic cell detection and the different expression of HMGB1
      protein were also assessed. Results Serum levels of aminotransferases, cytokines
      and hepatic MPO in UPC and UPC+anti-HMGB1 groups were significantly lower than
      those in control group (p<0.05). Decreased histologic damage and apoptosis were
      also seen in these two groups (p<0.05). Conclusions HMGB1 expressions in UPC and
      UPC+anti-HMGB1 groups were significantly lower than those in the two control
      groups (p<0.05), pretreatment with ulinastatin attenuated liver IR injury by
      reducing HMGB1 expression through its anti-inflammatory effects. 

PMID- 24578611
TI  - Glial scar formation occurs in the human brain after ischemic stroke.
AB  - Reactive gliosis and glial scar formation have been evidenced in the animal model
      of ischemic stroke, but not in human ischemic brain. Here, we have found that
      GFAP, ED1 and chondroitin sulphate proteoglycans (CSPG) expression were
      significantly increased in the cortical peri-infarct regions after ischemic
      stroke, compared with adjacent normal tissues and control subjects. Double
      immunolabeling showed that GFAP-positive reactive astrocytes in the peri-infarct
      region expressed CSPG, but showed no overlap with ED1-positive activated
      microglia. Our findings suggest that reactive gliosis and glial scar formation as
      seen in animal models of stroke are reflective of what occurs in the human brain
      after an ischemic injury. 

PMID- 24578612
TI  - The relationships between thyroid hormones and thyroid-stimulating hormone with
      lipid profile in euthyroid men.
AB  - BACKGROUND AND AIM: Alteration in lipid profile is a common observation in
      patients with thyroid dysfunction, but the current knowledge on the relationship
      between lipids and thyroid hormone levels in euthyroid state is insufficient. The
      current study aimed to determine the association between thyroid hormones and
      thyroid-stimulating hormone (TSH) with lipid profile in a euthyroid male
      population. METHODS: A total of 708 Chinese and Malay men aged 20 years and above
      were recruited in this cross-sectional study. Their blood was collected for the
      determination of total cholesterol (TC), low density lipoprotein cholesterol (LDL
      C), high density lipoprotein cholesterol (HDL-C), triglyceride (TG), free
      thyroxine (FT4), free triiodothyronine (FT3) and TSH levels. The association was
      analyzed using multiple regression and logistic regression models with adjustment
      for age, ethnicity, body mass index and FT4/FT3/TSH levels. RESULTS: In multiple
      regression models, TSH was positively and significantly associated with TG
      (p<0.05). Free T4 was positively and significantly associated with TC, LDL-C and
      HDL-C (p<0.05). Free T3 was negatively and significantly associated with HDL-C
      (p<0.05). In binary logistic models, an increase in TSH was significantly
      associated with higher prevalence of elevated TG in the subjects (p<0.05), while
      an increase in FT4 was significantly associated with higher prevalence of
      elevated TC but a lower prevalence of subnormal HDL in the subjects (p<0.05).
      Free T3 was not associated with any lipid variables in the logistic regression
      (p>0.05). CONCLUSIONS: In euthyroid Malaysian men, there are positive and
      significant relationships between TSH level and TG level, and between FT4 level
      and cholesterol levels.

PMID- 24578613
TI  - Osteoclastogenic potential of peripheral blood mononuclear cells in cleidocranial
      dysplasia.
AB  - Cleidocranial dysplasia (CCD) is an autosomal dominant skeletal dysplasia
      characterized by hypoplastic or aplastic clavicles, dental abnormalities, and
      delayed closure of the cranial sutures. In addition, mid-face hypoplasia, short
      stature, skeletal anomalies and osteoporosis are common. We aimed to evaluate
      osteoclastogenesis in a child (4 years old), who presented with clinical signs of
      CCD and who have been diagnosed as affected by deletion of RUNX2, master gene in
      osteoblast differentiation, but also affecting T cell development and indirectly
      osteoclastogenesis. The results of this study may help to understand whether in
      this disease is present an alteration in the bone-resorptive cells, the
      osteoclasts (OCs). Unfractionated and T cell-depleted Peripheral Blood
      Mononuclear Cells (PBMCs) from patient were cultured in presence/absence of
      recombinant human M-CSF and RANKL. At the end of the culture period, OCs only
      developed following the addition of M-CSF and RANKL. Moreover, real-time PCR
      experiment showed that freshly isolated T cells expressed the osteoclastogenic
      cytokines (RANKL and TNFalpha) at very low level, as in controls. This is in
      accordance with results arising from flow cytometry experiments demonstrating an
      high percentage of circulating CD4(+)CD28(+) and CD4(+)CD27(+) T cells, not able
      to produce osteoclastogenic cytokines. Also RANKL, OPG and CTX serum levels in
      CCD patient are similar to controls, whereas QUS measurements showed an
      osteoporotic status (BTT-Z score -3.09) in the patient. In conclusions, our
      findings suggest that the heterozygous deletion of RUNX2 in this CCD patient did
      not alter the osteoclastogenic potential of PBMCs in vitro. 

PMID- 24578614
TI  - Decreased activities of apolipoprotein m promoter are associated with the
      susceptibility to coronary artery diseases.
AB  - The present study investigated the correlation among genetic polymorphisms of the
      proximal promoter region of apolipoprotein M (apoM) gene, the polymorphisms in
      relation to apoM expressions and the susceptibility to coronary artery diseases
      (CAD) in a Han Chinese population. Four common polymorphic sites, i.e., T-1628G,
      C-1065A, T-855C and T-778C, were confirmed, and a new deletion mutation C-724del
      was found, in 206 CAD patients and 209 non-CAD patients using direct DNA
      sequencing analyses. Occurrences of alleles T-1628G, T-855C and C-724del were
      significantly higher in CAD patients compared to non-CAD patients. Moreover we
      examined all these polymorphisms in relation to apoM expression by applying
      luciferase reporter assay. It demonstrated that constructs -855C and 724del
      showed obvious decreased luciferase activities, i.e., (0.93+/-0.15 vs. 2.11+/
      0.15; P=0.012) and (1.13+/-0.25 vs. 2.11+/-0.15; P=0.009) respectively, which
      indicates these two polymorphisms could confer decreased apoM expressions.
      Meanwhile the occurrences of these two SNP were also significantly higher in the
      CAD patients than in non-CAD patients. It is therefore reasonable to speculate
      that down-regulated apoM expressions in relation to these polymorphisms may
      affect HDL and cholesterol metabolism in vivo and further influence the
      susceptibility to CAD, although the underlying mechanisms need further
      investigation. 

PMID- 24578617
TI  - Influence of fuel moisture content and reactor temperature on the calorific value
      of syngas resulted from gasification of oil palm fronds.
AB  - Biomass wastes produced from oil palm mills and plantations include empty fruit
      bunches (EFBs), shells, fibers, trunks, and oil palm fronds (OPF). EFBs and
      shells are partially utilized as boiler fuel while the rest of the biomass
      materials like OPF have not been utilized for energy generation. No previous
      study has been reported on gasification of oil palm fronds (OPF) biomass for the
      production of fuel gas. In this paper, the effect of moisture content of fuel and
      reactor temperature on downdraft gasification of OPF was experimentally
      investigated using a lab scale gasifier of capacity 50 kW. In addition, results
      obtained from equilibrium model of gasification that was developed for
      facilitating the prediction of syngas composition are compared with experimental
      data. Comparison of simulation results for predicting calorific value of syngas
      with the experimental results showed a satisfactory agreement with a mean error
      of 0.1 MJ/Nm3. For a biomass moisture content of 29%, the resulting calorific
      value for the syngas was found to be only 2.63 MJ/Nm3, as compared to nearly
      double (4.95 MJ/Nm3) for biomass moisture content of 22%. A calorific value as
      high as 5.57 MJ/Nm3 was recorded for higher oxidation zone temperature values.

PMID- 24578615
TI  - Endothelin-1 promotes cardiomyocyte terminal differentiation in the developing
      heart via heightened DNA methylation.
AB  - AIMS: Hypoxia is a major stress on fetal development and leads to induction of
      endothelin-1 (ET-1) expression. We tested the hypothesis that ET-1 stimulates the
      terminal differentiation of cardiomyocytes from mononucleate to binucleate in the
      developing heart. METHODS AND RESULTS: Hypoxia (10.5% O2) treatment of pregnant
      rats from day 15 to day 21 resulted in a significant increase in prepro-ET-1 mRNA
      expression in fetal hearts. ET-1 ex vivo treatment of fetal rat cardiomyocytes
      increased percent binucleate cells and decreased Ki-67 expression, a marker for
      proliferation, under both control and hypoxic conditions. Hypoxia alone decreased
      Ki-67 expression and in conjunction with ET-1 treatment decreased cardiomyocyte
      size. PD145065, a non-selective ET-receptor antagonist, blocked the changes in
      binucleation and proliferation caused by ET-1. DNA methylation in fetal
      cardiomyocytes was significantly increased with ET-1 treatment, which was blocked
      by 5-aza-2'-deoxycytidine, a DNA methylation inhibitor. In addition, 5-aza-2'
      deoxycytidine treatment abrogated the increase in binucleation and decrease in
      proliferation induced by ET-1. CONCLUSIONS: Hypoxic stress and synthesis of ET-1
      increases DNA methylation and promotes terminal differentiation of cardiomyocytes
      in the developing heart. This premature exit of the cell cycle may lead to a
      reduced cardiomyocyte endowment in the heart and have a negative impact on
      cardiac function.

PMID- 24578616
TI  - The impact of chronic kidney disease on lipid management and goal attainment in
      patients with atherosclerosis diseases in Taiwan.
AB  - BACKGROUND: Patients with chronic kidney disease (CKD) is a very high risk
      cardiovascular disease population and should be treated aggressively. We
      investigated lipid management in CKD patients with atherosclerosis in Taiwan.
      METHODS: 3057 patients were enrolled in a multi-center study (T-SPARCLE). Lipid
      goal are defined as total cholesterol (TC) < 160mg/dl, low-density lipoprotein
      (LDL) <100 mg/dl, high-density lipoprotein (HDL) > 40 mg/dl in men, HDL > 50
      mg/dl in women, non-HDL cholesterol < 130mg/dl, and triglyceride < 150 mg/dl.
      RESULTS: Compared with those without CKD (n=2239), patients with CKD (n=818) had
      more co-morbidities (hypertension, glucose intolerance, stroke and heart failure)
      and lower HDL but higher triglyceride levels. Overall 2168 (70.5%) patients
      received lipid-lowering agents. There was similar equivalent statin potency
      between CKD and non-CKD groups. The goal attainment is lower in HDL and TG in the
      CKD group as compared with non-CKD subjects (47.1 vs. 51.9% and 63.2 vs. 68.9%
      respectively, both p < 0.02). Analysis of sex and CKD interaction on goals
      attainment showed female CKD subjects had lower non-HDL and TG goals attainment
      compared with non-CKD males (both p < 0.019). CONCLUSION: Although presenting
      with more comorbidities, the CKD population had suboptimal lipid goal attainment
      rate as compared with the non-CKD population. Further efforts may be required for
      better lipid control especially on the female CKD subjects.

PMID- 24578618
TI  - Genotypic diversity and virulence traits of Streptococcus mutans isolated from
      carious dentin after partial caries removal and sealing.
AB  - The aim of this study was to compare the genotypic diversity and virulence traits
      of Streptococcus mutans isolated from carious dentin before and after partial
      dentin caries removal (PDR) and sealing. Carious dentin samples were obtained
      three months before and after the PDR and cavity sealing. Up to seven isolates of
      each morphological type of S. mutans were selected and strain identity was
      confirmed using gtfB primer. Genotyping was performed by arbitrary primer-PCR (AP
      PCR). Acidogenesis and acidurance of the genotypes were evaluated as virulence
      traits. A paired t-test and a Wilcoxon test were used to compare the virulence of
      genotypes. A total of 48 representative S. mutans isolates were genotyped (31
      before and 17 after the sealing). At least one of the genotypes found before the
      sealing was also found on dentin after the sealing. The number of genotypes found
      before the sealing ranged from 2 to 3 and after the sealing from 1 to 2
      genotypes. No difference was observed in the acidogenesis and acidurance between
      genotypes isolated before and after the sealing. In conclusion, genotypic
      diversity of S. mutans decreased after the PDR and sealing, but the virulence
      traits of S. mutans remained unchangeable. 

PMID- 24578619
TI  - Removal of the 2-mercaptobenotiazole from model wastewater by ozonation.
AB  - The feasibility of ozonation process for 2-mercaptobenzothiazole (2-MBT) removal
      follows from results of ozonation of the model wastewater. Total removal of 2-MBT
      was observed after 20 minutes of ozonation. Very good reproducibility of repeated
      ozonation trials including sampling and analysis was observed. However, the
      majority of dissolved organic carbon (DOC) and chemical oxygen demand (COD)
      remained in the reaction mixture. Benzothiazole (BT) and 2-hydroxybenzothiazole
      (OBT) intermediates were identified during degradation of 2-MBT with ozone. In
      addition to the above benzothiazole derivatives, the creation of some other
      organic compounds follows from results of mass balance. The best fits of
      experimental data were obtained using the first kinetic model for 2-MBT and zero
      order kinetic model for COD and DOC. The reaction time of 60 minutes can be
      considered as effective with regard to controlled oxidation in order to increase
      a portion of partially oxidized substances. Higher biodegradability and lower
      toxicity of ozonation products on respiration activity of activated sludge
      microorganisms was observed at higher ozonation time. 

PMID- 24578621
TI  - Time-lapse electrical resistivity investigations for imaging the grouting
      injection in shallow subsurface cavities.
AB  - The highway of Yongweol-ri, Muan-gun, south-western part of the South Korean
      Peninsula, is underlain by the abandoned of subsurface cavities, which were
      discovered in 2005. These cavities lie at shallow depths with the range of 5~15
      meters below the ground surface. Numerous subsidence events have repeatedly
      occurred in the past few years, damaging infrastructure and highway. As a result
      of continuing subsidence issues, the Korean Institute of Geosciences and Mineral
      Resources (KIGAM) was requested by local administration to resolve the issue. The
      KIGAM used geophysical methods to delineate subsurface cavities and improve more
      refined understanding of the cavities network in the study area. Cement based
      grouting has been widely employed in the construction industry to reinforce
      subsurface ground. In this research work, time-lapse electrical resistivity
      surveys were accomplished to monitor the grouting injection in the subsurface
      cavities beneath the highway, which have provided a quasi-real-time monitoring
      for modifying the subsurface cavities related to ground reinforcement, which
      would be difficult with direct methods. The results obtained from time-lapse
      electrical resistivity technique have satisfactory imaged the grouting injection
      experiment in the subsurface cavities beneath the highway. Furthermore, the
      borehole camera confirmed the presence of grouting material in the subsurface
      cavities, and hence this procedure increases the mechanical resistance of
      subsurface cavities below the highway.

PMID- 24578623
TI  - A study of impulsive multiterm fractional differential equations with single and
      multiple base points and applications.
AB  - We discuss the existence and uniqueness of solutions for initial value problems
      of nonlinear singular multiterm impulsive Caputo type fractional differential
      equations on the half line. Our study includes the cases for a single base point
      fractional differential equation as well as multiple base points fractional
      differential equation. The asymptotic behavior of solutions for the problems is
      also investigated. We demonstrate the utility of our work by applying the main
      results to fractional-order logistic models. 

PMID- 24578620
TI  - Curcumin as a therapeutic agent in dementia: a mini systematic review of human
      studies.
AB  - Dementia is a leading health problem worldwide, with Alzheimer's disease (AD)
      representing up to 60% of all dementia cases. A growing interest has recently
      risen on the potential use of natural molecules in this condition. Curcumin is a
      polyphenolic compound traditionally used in Indian medicine. Several in vitro and
      in vivo studies have found a protective effect of curcumin in AD. In the present
      systematic review we aimed to evaluate the state-of-the-art of clinical trials of
      curcumin in AD. We retrieved three published studies, while there are several
      ongoing clinical trials. To date there is insufficient evidence to suggest the
      use of curcumin in dementia patients. Of note, short-term use of curcumin appears
      to be safe. Several reasons could be responsible for the discrepancy between in
      vitro and in vivo findings and human trials, such as low bioavailability and poor
      study design. 

PMID- 24578622
TI  - Pre-conditioning with CDP-choline attenuates oxidative stress-induced cardiac
      myocyte death in a hypoxia/reperfusion model.
AB  - BACKGROUND: CDP-choline is a key intermediate in the biosynthesis of
      phosphatidylcholine, which is an essential component of cellular membranes, and a
      cell signalling mediator. CDP-choline has been used for the treatment of cerebral
      ischaemia, showing beneficial effects. However, its potential benefit for the
      treatment of myocardial ischaemia has not been explored yet. AIM: In the present
      work, we aimed to evaluate the potential use of CDP-choline as a cardioprotector
      in an in vitro model of ischaemia/reperfusion injury. METHODS: Neonatal rat
      cardiac myocytes were isolated and subjected to hypoxia/reperfusion using the
      coverslip hypoxia model. To evaluate the effect of CDP-choline on oxidative
      stress-induced reperfusion injury, the cells were incubated with H2O2 during
      reperfusion. The effect of CDP-choline pre- and postconditioning was evaluated
      using the cell viability MTT assay, and the proportion of apoptotic and necrotic
      cells was analyzed using the Annexin V determination by flow cytometry. RESULTS:
      Pre- and postconditioning with 50 mg/mL of CDP-choline induced a significant
      reduction of cells undergoing apoptosis after hypoxia/reperfusion.
      Preconditioning with CDP-choline attenuated postreperfusion cell death induced by
      oxidative stress. CONCLUSION: CDP-choline administration reduces cell apoptosis
      induced by oxidative stress after hypoxia/reperfusion of cardiac myocytes. Thus,
      it has a potential as cardioprotector in ischaemia/reperfusion-injured
      cardiomyocytes.

PMID- 24578624
TI  - Development of a controlled release of salicylic acid loaded stearic acid-oleic
      acid nanoparticles in cream for topical delivery.
AB  - Lipid nanoparticles are colloidal carrier systems that have extensively been
      investigated for controlled drug delivery, cosmetic and pharmaceutical
      applications. In this work, a cost effective stearic acid-oleic acid
      nanoparticles (SONs) with high loading of salicylic acid, was prepared by melt
      emulsification method combined with ultrasonication technique. The
      physicochemical properties, thermal analysis and encapsulation efficiency of SONs
      were studied. TEM micrographs revealed that incorporation of oleic acid induces
      the formation of elongated spherical particles. This observation is in agreement
      with particle size analysis which also showed that the mean particle size of SONs
      varied with the amount of OA in the mixture but with no effect on their zeta
      potential values. Differential scanning calorimetry analysis showed that the SONs
      prepared in this method have lower crystallinity as compared to pure stearic
      acid. Different amount of oleic acid incorporated gave different degree of
      perturbation to the crystalline matrix of SONs and hence resulted in lower
      degrees of crystallinity, thereby improving their encapsulation efficiencies. The
      optimized SON was further incorporated in cream and its in vitro release study
      showed a gradual release for 24 hours, denoting the incorporation of salicylic
      acid in solid matrix of SON and prolonging the in vitro release. 

PMID- 24578625
TI  - Association of leukocytosis with amphetamine and cocaine use.
AB  - OBJECTIVE: Determining the etiology of unexplained leukocytosis in asymptomatic
      patients may incur unnecessary testing, cost, and prolonged emergency department
      stay. The objective was to delineate if use of amphetamines and/or cocaine is a
      factor. METHODS: For two years we reviewed all psychiatric patients presenting
      for medical clearance with exclusions for infection, epilepsy, trauma, or other
      nonpsychiatric medical conditions. RESULTS: With a total of 1,206 patients, 877
      (72.7%) amphetamines/cocaine-negative drug screen controls had mean WBC 8.4 +/-
      2.6 * 103/uL. The 240 (19.9%) amphetamines-positive, cocaine-negative, patients
      had WBC 9.4 +/- 3.3 * 103/uL (P < 0.0001). The 72 (6.0%) amphetamines-negative,
      cocaine-positive, patients had WBC 7.1 +/- 1.8 * 103/uL (P < 0.0001). The
      remaining 17 (1.4%) amphetamines/cocaine-positive patients had WBC 10.0 +/- 4.2 *
      103/uL (P = 0.01). Amphetamines-positive patients had a supranormal WBC ratio
      significantly higher than controls (23.8% versus 14.8%, P = 0.001), whereas only
      one cocaine-positive patient had a supranormal WBC count, with significantly
      lower ratio (1.4%, P = 0.0003). CONCLUSION: Use of amphetamines, not cocaine, may
      be associated with idiopathic leukocytosis. This may be explained by unique
      pharmacologic, neuroendocrine, and immunomodulatory differences.

PMID- 24578626
TI  - Genetic variability and phylogeny of current Chinese porcine epidemic diarrhea
      virus strains based on spike, ORF3, and membrane genes.
AB  - Since late 2010, the outbreak of porcine epidemic diarrhea (PED) in China has
      resulted in the deaths of millions of suckling piglets. The main cause of the
      disease outbreak was unknown. In this study, partial spike (S), ORF3, and
      membrane (M) genes amplified from these variants were sequenced and analyzed. The
      results showed that the variants could be clustered into one to three subgroups
      and suggested that S genes were variable, while M genes were relatively
      conserved. Moreover, in comparison with the vaccine strain CV777, sequence
      alignment analyses revealed that the S genes of the newly isolated strains
      contained several mutations at the aa level. It is possible that these mutations
      have changed the hydrophobicity of the S protein and influenced the viral
      antigenicity and virulence. Interestingly, homology analyses based on ORF3
      demonstrated that the isolates had an intact opening reading frame (ORF), which
      were different from the attenuated DR13 strain. In conclusion, the widespread PED
      virus (PEDV) isolates had virulent characteristics. Additionally, the high degree
      of variation in the genes, particularly S genes, might provide an explanation for
      the poor immunity and rapid spread of the disease. 

PMID- 24578628
TI  - Microwave synthesis, characterization, and photoluminescence properties of
      nanocrystalline zirconia.
AB  - We report synthesis of ZrO2 nanoparticles (NPs) using microwave assisted chemical
      method at 80 degrees C temperature. Synthesized ZrO2 NPs were calcinated at 400
      degrees C under air atmosphere and characterized using FTIR, XRD, SEM, TEM, BET,
      and EDS for their formation, structure, morphology, size, and elemental
      composition. XRD results revealed the formation of mixed phase monoclinic and
      tetragonal ZrO2 phases having crystallite size of the order 8.8 nm from most
      intense XRD peak as obtained using Scherrer formula. Electron microscope analysis
      shows that the NPs were less than 10 nm and highly uniform in size having
      spherical morphology. BET surface area of ZrO2 NPs was found to be 65.85 m2/g
      with corresponding particle size of 16 nm. The band gap of synthesized NPs was
      found to be 2.49 eV and PL spectra of ZrO2 synthesized NPs showed strong peak at
      414 nm, which corresponds to near band edge emission (UV emission) and a
      relatively weak peak at 475 and 562 nm.

PMID- 24578627
TI  - Eyes as gateways for environmental light to the substantia nigra: relevance in
      Parkinson's disease.
AB  - Recent data indicates that prolonged bright light exposure of rats induces
      production of neuromelanin and reduction of tyrosine hydroxylase positive neurons
      in the substantia nigra. This effect was the result of direct light reaching the
      substantia nigra and not due to alteration of circadian rhythms. Here, we
      measured the spectrum of light reaching the substantia nigra in rats and analysed
      the pathway that light may take to reach this deep brain structure in humans.
      Wavelength range and light intensity, emitted from a fluorescent tube, were
      measured, using a stereotaxically implanted optical fibre in the rat
      mesencephalon. The hypothetical path of environmental light from the eye to the
      substantia nigra in humans was investigated by computed tomography and magnetic
      resonance imaging. Light with wavelengths greater than 600 nm reached the rat
      substantia nigra, with a peak at 709 nm. Eyes appear to be the gateway for light
      to the mesencephalon since covering the eyes with aluminum foil reduced light
      intensity by half. Using computed tomography and magnetic resonance imaging of a
      human head, we identified the eye and the superior orbital fissure as possible
      gateways for environmental light to reach the mesencephalon. 

PMID- 24578629
TI  - DERMA: a melanoma diagnosis platform based on collaborative multilabel analog
      reasoning.
AB  - The number of melanoma cancer-related death has increased over the last few years
      due to the new solar habits. Early diagnosis has become the best prevention
      method. This work presents a melanoma diagnosis architecture based on the
      collaboration of several multilabel case-based reasoning subsystems called DERMA.
      The system has to face up several challenges that include data characterization,
      pattern matching, reliable diagnosis, and self-explanation capabilities.
      Experiments using subsystems specialized in confocal and dermoscopy images have
      provided promising results for helping experts to assess melanoma diagnosis. 

PMID- 24578630
TI  - Early stage design decisions: the way to achieve sustainable buildings at lower
      costs.
AB  - The construction industry attempts to produce buildings with as lower
      environmental impact as possible. However, construction activities still greatly
      affect environment; therefore, it is necessary to consider a sustainable project
      approach based on its performance. Sustainability is an important issue to
      consider in design, not only due to environmental concerns but also due to
      economic and social matters, promoting architectural quality and economic
      advantages. This paper aims to identify the phases through which a design project
      should be developed, emphasising the importance and ability of earlier stages to
      influence sustainability, performance, and life cycle cost. Then, a selection of
      sustainability key indicators, able to be used at the design conceptual phase and
      able to start predicting environmental sustainability performance of buildings is
      presented. The output of this paper aimed to enable designers to compare and
      evaluate the consequences of different design solutions, based on preliminary
      data, and facilitate the collaboration between stakeholders and clients and
      eventually yield a sustainable and high performance building throughout its life
      cycle. 

PMID- 24578631
TI  - Studies on Emblica officinalis derived tannins for their immunostimulatory and
      protective activities against coccidiosis in industrial broiler chickens.
AB  - The present study reports the effect of Emblica officinalis (EO) derived tannins
      on humoral immune responses and their protective efficacy against Eimeria
      infection in chickens. Tannins were extracted from EO and characterized by HPLC.
      EO derived tannins (EOT) and commercial tannins (CT) were orally administered in
      broiler chicks in graded doses for three consecutive days, that is, 5th-7th days
      of age. On day 14 after administration of tannins, humoral immune response was
      detected against sheep red blood cells (SRBCs) by haemagglutination assay.
      Protective efficacy of tannins was measured against coccidial infection, induced
      by Eimeria species. Results revealed higher geomean titers against SRBCs in
      chickens administered with EOT as compared to those administered with CT and
      control group. Mean oocysts per gram of droppings were significantly lower (P <
      0.05) in EOT administered chickens as compared to control group. Lesion scoring
      also showed the lowest caecal and intestinal lesion score of mild to moderate
      intensity in chickens administered with EOT. Further, significantly higher (P <
      0.05) daily body weight gains and antibody titers were detected in EOT
      administered chickens as compared to those of CT administered and control groups.
      EOT showed the immunostimulatory properties in broilers and their administration
      in chickens boost the protective immunity against coccidiosis. 

PMID- 24578632
TI  - Prognostic implication of preoperative behavior changes in patients with primary
      high-grade meningiomas.
AB  - High-grade meningiomas are rare extra-axial tumors, frequently causing brain
      invasion and prominent brain edema. Patients harboring high-grade meningiomas
      occasionally present with behavior changes. Data about frequency and prognostic
      importance of preoperative behavior changes in patients with high-grade
      meningiomas is missing. 86 patients with primary high-grade meningiomas were
      analyzed. Statistical analysis was performed to determine correlation of
      preoperative behavior changes with tumor location, preoperative brain edema,
      tumor cleavability, tumor grade, Ki67 proliferation index, and microscopic brain
      invasion. Survival analysis was performed. 30 (34.9%) patients presented with
      preoperative behavior changes. These changes were more frequent with male
      patients (P = 0.066) and patients older than 55 years (P = 0.018). They
      correlated with frontal location (P = 0.013), tumor size (P = 0.023), microscopic
      brain invasion (P = 0.015), and brain edema (P = 0.006). Preoperative behavior
      changes did not correlate with duration of symptoms, tumor cleavability, tumor
      malignancy grade, and Ki67 proliferation index. They were not significantly
      related to overall survival or recurrence-free survival of patients with primary
      high-grade meningiomas. Preoperative behavior changes are frequent in patients
      harboring primary high-grade meningiomas. They correlate with tumor size,
      microscopic brain invasion, and brain edema. Preoperative behavior changes do not
      predict prognosis in patients with primary high-grade meningiomas. 

PMID- 24578634
TI  - A web-server of cell type discrimination system.
AB  - Discriminating cell types is a daily request for stem cell biologists. However,
      there is not a user-friendly system available to date for public users to
      discriminate the common cell types, embryonic stem cells (ESCs), induced
      pluripotent stem cells (iPSCs), and somatic cells (SCs). Here, we develop WCTDS,
      a web-server of cell type discrimination system, to discriminate the three cell
      types and their subtypes like fetal versus adult SCs. WCTDS is developed as a top
      layer application of our recent publication regarding cell type discriminations,
      which employs DNA-methylation as biomarkers and machine learning models to
      discriminate cell types. Implemented by Django, Python, R, and Linux shell
      programming, run under Linux-Apache web server, and communicated through MySQL,
      WCTDS provides a friendly framework to efficiently receive the user input and to
      run mathematical models for analyzing data and then to present results to users.
      This framework is flexible and easy to be expended for other applications.
      Therefore, WCTDS works as a user-friendly framework to discriminate cell types
      and subtypes and it can also be expended to detect other cell types like cancer
      cells. 

PMID- 24578635
TI  - Hysteretic behavior of prestressed concrete bridge pier with fiber model.
AB  - The hysteretic behavior and seismic characteristics of the prestressed concrete
      bridge pier were researched. The effects of the prestressed tendon ratio, the
      longitudinal reinforcement ratio, and the stirrup reinforcement ratio on the
      hysteretic behavior and seismic characteristics of the prestressed concrete
      bridge pier have been obtained with the fiber model analysis method. The analysis
      show some results about the prestressed concrete bridge pier. Firstly, greater
      prestressed tendon ratio and more longitudinal reinforcement can lead to more
      obvious pier's hysteresis loop "pinching effect," smaller residual displacement,
      and lower energy dissipation capacity. Secondly, the greater the stirrup
      reinforcement ratio is, the greater the hysteresis loop area is. That also means
      that bridge piers will have better ductility and stronger shear capacity. The
      results of the research will provide a theoretical basis for the hysteretic
      behavior analysis of the prestressed concrete pier. 

PMID- 24578633
TI  - Emergence of enteric viruses in production chickens is a concern for avian
      health.
AB  - Several viruses have been identified in recent years in the intestinal contents
      of chickens and turkeys with enteric problems, which have been observed in
      commercial farms worldwide, including Brazil. Molecular detection of these
      viruses in Brazil can transform to a big threat for poultry production due to
      risk for intestinal integrity. This disease is characterized by severely delayed
      growth, low uniformity, lethargy, watery diarrhea, delayed feed consumption, and
      a decreased conversion rate. Chicken astrovirus (CAstV), rotavirus, reovirus,
      chicken parvovirus (ChPV), fowl adenovirus of subgroup I (FAdV-1), and avian
      nephritis virus (ANV) were investigated using the conventional polymerase chain
      reaction (PCR) and the reverse transcription polymerase chain reaction (RT-PCR).
      In addition, the infectious bronchitis virus (IBV), which may play a role in
      enteric disease, was included. The viruses most frequently detected, either alone
      or in concomitance with other viruses, were IBV, ANV, rotavirus, and CAstV
      followed by parvovirus, reovirus, and adenovirus. This study demonstrates the
      diversity of viruses in Brazilian chicken flocks presenting enteric problems
      characterized by diarrhea, growth retard, loss weight, and mortality, which
      reflects the multicausal etiology of this disease. 

PMID- 24578636
TI  - Surface roughness optimization of polyamide-6/nanoclay nanocomposites using
      artificial neural network: genetic algorithm approach.
AB  - During the past decade, polymer nanocomposites attracted considerable investment
      in research and development worldwide. One of the key factors that affect the
      quality of polymer nanocomposite products in machining is surface roughness. To
      obtain high quality products and reduce machining costs it is very important to
      determine the optimal machining conditions so as to achieve enhanced machining
      performance. The objective of this paper is to develop a predictive model using a
      combined design of experiments and artificial intelligence approach for
      optimization of surface roughness in milling of polyamide-6 (PA-6)
      nanocomposites. A surface roughness predictive model was developed in terms of
      milling parameters (spindle speed and feed rate) and nanoclay (NC) content using
      artificial neural network (ANN). As the present study deals with relatively small
      number of data obtained from full factorial design, application of genetic
      algorithm (GA) for ANN training is thought to be an appropriate approach for the
      purpose of developing accurate and robust ANN model. In the optimization phase, a
      GA is considered in conjunction with the explicit nonlinear function derived from
      the ANN to determine the optimal milling parameters for minimization of surface
      roughness for each PA-6 nanocomposite. 

PMID- 24578637
TI  - Invasive and ultrasound based monitoring of the intracranial pressure in an
      experimental model of epidural hematoma progressing towards brain tamponade on
      rabbits.
AB  - INTRODUCTION: An experimental epidural hematoma model was used to study the
      relation of ultrasound indices, namely, transcranial color-coded-Doppler (TCCD)
      derived pulsatility index (PI), optic nerve sheath diameter (ONSD), and pupil
      constriction velocity (V) which was derived from a consensual sonographic
      pupillary light reflex (PLR) test with invasive intracranial pressure (ICP)
      measurements. MATERIAL AND METHODS: Twenty rabbits participated in the study. An
      intraparenchymal ICP catheter and a 5F Swan-Ganz catheter (SG) for the hematoma
      reproduction were used. We successively introduced 0.1 mL increments of
      autologous blood into the SG until the Cushing reaction occurred. Synchronous ICP
      and ultrasound measurements were performed accordingly. RESULTS: A constant
      increase of PI and ONSD and a decrease of V values were observed with increased
      ICP values. The relationship between the ultrasound variables and ICP was
      exponential; thus curved prediction equations of ICP were used. PI, ONSD, and V
      were significantly correlated with ICP (r2 = 0.84 +/- 0.076, r2 = 0.62 +/- 0.119,
      and r2 = 0.78 +/- 0.09, resp. (all P < 0.001)). CONCLUSION: Although
      statistically significant prediction models of ICP were derived from ultrasound
      indices, the exponential relationship between the parameters underpins that
      results should be interpreted with caution and in the current experimental
      context.

PMID- 24578638
TI  - Preparation, characterization, and enhanced thermal and mechanical properties of
      epoxy-titania composites.
AB  - This paper presents the synthesis and thermal and mechanical properties of epoxy
      titania composites. First, submicron titania particles are prepared via
      surfactant-free sol-gel method using TiCl4 as precursor. These particles are
      subsequently used as inorganic fillers (or reinforcement) for thermally cured
      epoxy polymers. Epoxy-titania composites are prepared via mechanical mixing of
      titania particles with liquid epoxy resin and subsequently curing the mixture
      with an aliphatic diamine. The amount of titania particles integrated into epoxy
      matrix is varied between 2.5 and 10.0 wt.% to investigate the effect of sub
      micron titania particles on thermal and mechanical properties of epoxy-titania
      composites. These composites are characterized by X-ray photoelectron (XPS)
      spectroscopy, scanning electron microscopy (SEM), differential scanning
      calorimetry (DSC), thermogravimetric (TG), and mechanical analyses. It is found
      that sub-micron titania particles significantly enhance the glass transition
      temperature (>6.7%), thermal oxidative stability (>12.0%), tensile strength
      (>21.8%), and Young's modulus (>16.8%) of epoxy polymers. Epoxy-titania
      composites with 5.0 wt.% sub-micron titania particles perform best at elevated
      temperatures as well as under high stress.

PMID- 24578640
TI  - Protein-protein interactions prediction based on iterative clique extension with
      gene ontology filtering.
AB  - Cliques (maximal complete subnets) in protein-protein interaction (PPI) network
      are an important resource used to analyze protein complexes and functional
      modules. Clique-based methods of predicting PPI complement the data defection
      from biological experiments. However, clique-based predicting methods only depend
      on the topology of network. The false-positive and false-negative interactions in
      a network usually interfere with prediction. Therefore, we propose a method
      combining clique-based method of prediction and gene ontology (GO) annotations to
      overcome the shortcoming and improve the accuracy of predictions. According to
      different GO correcting rules, we generate two predicted interaction sets which
      guarantee the quality and quantity of predicted protein interactions. The
      proposed method is applied to the PPI network from the Database of Interacting
      Proteins (DIP) and most of the predicted interactions are verified by another
      biological database, BioGRID. The predicted protein interactions are appended to
      the original protein network, which leads to clique extension and shows the
      significance of biological meaning. 

PMID- 24578641
TI  - Membrane properties involved in calcium-stimulated microparticle release from the
      plasma membranes of S49 lymphoma cells.
AB  - This study answered the question of whether biophysical mechanisms for
      microparticle shedding discovered in platelets and erythrocytes also apply to
      nucleated cells: cytoskeletal disruption, potassium efflux, transbilayer
      phospholipid migration, and membrane disordering. The calcium ionophore,
      ionomycin, disrupted the actin cytoskeleton of S49 lymphoma cells and produced
      rapid release of microparticles. This release was significantly inhibited by
      interventions that impaired calcium-activated potassium current. Microparticle
      release was also greatly reduced in a lymphocyte cell line deficient in the
      expression of scramblase, the enzyme responsible for calcium-stimulated
      dismantling of the normal phospholipid transbilayer asymmetry. Rescue of the
      scrambling function at high ionophore concentration also resulted in enhanced
      particle shedding. The effect of membrane physical properties was addressed by
      varying the experimental temperature (32-42 degrees C). A significant positive
      trend in the rate of microparticle release as a function of temperature was
      observed. Fluorescence experiments with trimethylammonium diphenylhexatriene and
      Patman revealed significant decrease in the level of apparent membrane order
      along that temperature range. These results demonstrated that biophysical
      mechanisms involved in microparticle release from platelets and erythrocytes
      apply also to lymphocytes.

PMID- 24578639
TI  - Transforming growth factor-beta and matrix metalloproteinases: functional
      interactions in tumor stroma-infiltrating myeloid cells.
AB  - Transforming growth factor-beta (TGF-beta) is a pleiotropic factor with several
      different roles in health and disease. In tumorigenesis, it may act as a
      protumorigenic factor and have a profound impact on the regulation of the immune
      system response. Matrix metalloproteinases (MMPs) are a family that comprises
      more than 25 members, which have recently been proposed as important regulators
      acting in tumor stroma by regulating the response of noncellular and cellular
      microenvironment. Tumor stroma consists of several types of resident cells and
      infiltrating cells derived from bone marrow, which together play crucial roles in
      the promotion of tumor growth and metastasis. In cancer cells, TGF-beta regulates
      MMPs expression, while MMPs, produced by either cancer cells or residents' stroma
      cells, activate latent TGF-beta in the extracellular matrix, together
      facilitating the enhancement of tumor progression. In this review we will focus
      on the compartment of myeloid stroma cells, such as tumor-associated macrophages,
      neutrophils, and dendritic and mast cells, which are potently regulated by TGF
      beta and produce large amounts of MMPs. Their interplay and mutual implications
      in the generation of pro-tumorigenic cancer microenvironment will be analyzed.

PMID- 24578642
TI  - Isoprenaline: a potential contributor in sick sinus syndrome--insights from a
      mathematical model of the rabbit sinoatrial node.
AB  - The mechanism of isoprenaline exerting its effects on cardiac pacemaking and
      driving in sick sinus syndrome is controversial and unresolved. In this paper,
      mathematical models for rabbit sinoatrial node cells were modified by
      incorporating equations for the known dose-dependent actions of isoprenaline on
      various ionic channel currents, the intracellular Ca2+ transient, and i(Na)
      changes induced by SCN5A gene mutations; the cell models were also incorporated
      into an intact SAN-atrium model of the rabbit heart that is based on both
      heterogeneities of the SAN electrophysiology and histological structure. Our
      results show that, in both central and peripheral cell models, isoprenaline could
      not only shorten the action potential duration, but also increase the amplitude
      of action potential. The mutation impaired the SAN pacemaking. Simulated vagal
      nerve activity amplified the bradycardic effects of the mutation. However, in
      tissue case, the pacemaker activity may show temporal, spatial, or even
      spatiotemporal cessation caused by the mutation. Addition of isoprenaline could
      significantly diminish the bradycardic effect of the mutation and the SAN could
      restart pacing and driving the surrounding tissue. Positive effects of
      isoprenaline may primarily be attributable to an increase in i(Na) and i(Ca,T)
      which were reduced by the mutation.

PMID- 24578643
TI  - Seasonality influence on biochemical and hematological indicators of stress and
      growth of pirarucu (Arapaima gigas), an Amazonian air-breathing fish.
AB  - Environmental factors such as seasonal cycles are the main chronic stress cause
      in fish increasing incidence of disease and mortality and affecting productive
      performance. Arapaima gigas (pirarucu) is an Amazonian air-breathing and largest
      freshwater fish with scales in the world. The captivity development of pirarucu
      is expanding since it can fatten up over 1 kg per month reaching 10 kg body mass
      in the first year of fattening. This work was conducted in three periods (April
      to July 2010, August to November 2010, and December 2010 to March 2011) defined
      according to rainfall and medium temperatures. Seasonality effect analysis was
      performed on biochemical (lectin activity, lactate dehydrogenase, and alkaline
      phosphatase activities) and hematological (total count of red blood cells,
      hematocrit, hemoglobin, and hematimetric Wintrobe indexes) stress indicators, as
      well as on growth and wellbeing degree expressed by pirarucu condition factor
      developed in captivity. All biochemical and hematological stress indicators
      showed seasonal variations. However, the fish growth was allometrically positive;
      condition factor high values indicated good state of healthiness in cultivation.
      These results reinforce the robust feature of pirarucu and represent a starting
      point for understanding stress physiology and environmental changes during
      cultivation enabling identification and prevention of fish adverse health
      conditions. 

PMID- 24578644
TI  - OPCW Proficiency Test: a practical approach also for interlaboratory test on
      detection and identification of pesticides in environmental matrices.
AB  - An overview of general strategy, standard procedures, and critical points, which
      may be found during carrying out an OPCW Proficiency Test concerning detection
      and identification of scheduled compounds relevant to Chemical Weapon Convention,
      has been presented. The observations have been illustrated following the case of
      the Eight OPCW Designated Laboratories Proficiency Test, which was performed in
      the OPCW Laboratory in Rijswijk in November and December 2000. Various useful
      hints, comments, and practical observations concerning the case study have been
      included as well. The same methodology and procedures may be also applied for
      detection, identification, and environmental analyses of pesticides and biocides,
      especially organophosphorus compounds. 

PMID- 24578645
TI  - Brachiaria ruziziensis responses to different fertilization doses and to the
      attack of Mahanarva spectabilis (Hemiptera: Cercopidae) nymphs and adults.
AB  - Cropping practices are necessary in order to help reduce the population of pest
      insect, such as the induction of resistance through fertilization. Therefore,
      this study aimed to assess alterations on the production and quality of
      Brachiaria ruziziensis when receiving the fertilization composed by the
      macronutrients NPK and/or exposed to the attack of Mahanarva spectabilis nymphs
      and adults. B. ruziziensis plants were fertilized according to the recommendation
      (R), half of the recommended fertilization (H), or non-fertilization (C). They
      were also exposed to different M. spectabilis nymph and adult densities. The
      damage, regrowth, and bromatological components were evaluated. The fertilization
      treatment promoted a higher M. spectabilis nymph survival on B. ruziziensis;
      however, it reduced the damage caused by the forage exposed to nymphs and adults
      of pest insect, and it did not alter the quality of the signal grass. Moreover,
      the fertilization treatment enabled forage recovery, even when exposed to 5
      nymphs or 10 spittlebug adults. 

PMID- 24578646
TI  - Synthesis, characterization, and evaluation of a novel amphiphilic polymer RGD
      PEG-Chol for target drug delivery system.
AB  - An amphiphilic polymer RGD-PEG-Chol which can be produced in large scale at a
      very low cost has been synthesized successfully. The synthesized intermediates
      and final products were characterized and confirmed by 1H nuclear magnetic
      resonance spectrum (1H NMR) and Fourier transform infrared spectrum (FT-IR). The
      paclitaxel- (PTX-) loaded liposomes based on RGD-PEG-Chol were then prepared by
      film formation method. The liposomes had a size within 100 nm and significantly
      enhanced the cytotoxicity of paclitaxel to B16F10 cell as demonstrated by MTT
      test (IC50 = 0.079  MUg/mL of RGD-modified PTX-loaded liposomes compared to 9.57 
      MUg/mL of free PTX). Flow cytometry analysis revealed that the cellular uptake of
      coumarin encapsulated in the RGD-PEG-Chol modified liposome was increased for
      HUVEC cells. This work provides a reasonable, facile, and economic approach to
      prepare peptide-modified liposome materials with controllable performances and
      the obtained linear RGD-modified PTX-loaded liposomes might be attractive as a
      drug delivery system.

PMID- 24578647
TI  - Emerging risk factors and prevention of perioperative pulmonary complications.
AB  - Modern surgery is faced with the emergence of newer "risk factors" and the
      challenges associated with identifying and managing these risks in the
      perioperative period. Obstructive sleep apnea and obesity hypoventilation
      syndrome pose unique challenges in the perioperative setting. Recent studies have
      identified some of the specific risks arising from caring for such patients in
      the surgical setting. While all possible postoperative complications are not yet
      fully established or understood, the prevention and management of these
      complications pose even greater challenges. Pulmonary hypertension with its
      changing epidemiology and novel management strategies is another new disease for
      the surgeon and the anesthesiologist in the noncardiac surgical setting.
      Traditionally most such patients were not considered surgical candidates for any
      required elective surgery. Our review discusses these disease entities which are
      often undiagnosed before elective noncardiac surgery. 

PMID- 24578649
TI  - Ship trim optimization: assessment of influence of trim on resistance of MOERI
      container ship.
AB  - Environmental issues and rising fuel prices necessitate better energy efficiency
      in all sectors. Shipping industry is a stakeholder in environmental issues.
      Shipping industry is responsible for approximately 3% of global CO2 emissions, 14
      15% of global NO(X) emissions, and 16% of global SO(X) emissions. Ship trim
      optimization has gained enormous momentum in recent years being an effective
      operational measure for better energy efficiency to reduce emissions. Ship trim
      optimization analysis has traditionally been done through tow-tank testing for a
      specific hullform. Computational techniques are increasingly popular in ship
      hydrodynamics applications. The purpose of this study is to present MOERI
      container ship (KCS) hull trim optimization by employing computational methods.
      KCS hull total resistances and trim and sinkage computed values, in even keel
      condition, are compared with experimental values and found in reasonable
      agreement. The agreement validates that mesh, boundary conditions, and solution
      techniques are correct. The same mesh, boundary conditions, and solution
      techniques are used to obtain resistance values in different trim conditions at
      Fn = 0.2274. Based on attained results, optimum trim is suggested. This research
      serves as foundation for employing computational techniques for ship trim
      optimization.

PMID- 24578650
TI  - Controllability and observability of fractional linear systems with two different
      orders.
AB  - This paper is concerned with the controllability and observability for a class of
      fractional linear systems with two different orders. The sufficient and necessary
      conditions for state controllability and state observability of such systems are
      established. The results obtained extend some existing results of controllability
      and observability for fractional dynamical systems. 

PMID- 24578648
TI  - Effects of dietary milled seed mixture on fatty acid status and inflammatory
      markers in patients on hemodialysis.
AB  - BACKGROUND: Plant seeds have gained interest for their health benefits due to
      their fatty acid content. The objective of this study was to determine the
      effects of dietary consumption of milled sesame/pumpkin/flax seed mixture on
      glycemic control, serum lipids, phospholipid fatty acid status, and inflammatory
      factors in patients on hemodialysis. METHODS: Thirty patients with well nutrition
      status (18 male, 12 female) were enrolled in the study. Participants consumed 30
      g of milled sesame/pumpkin/flax (6 g/6 g/18 g, resp.) seeds mixture added to
      their habitual diet. RESULTS: Total n-6 and n-3 polyunsaturated fatty acids and
      levels of linoleic, dihomo-gamma-linolenic (DGLA), arachidonic, alpha-linolenic
      (ALA), eicosapentaenoic, docosapentaenoic, and docosahexaenoic (DHA) acid were
      increased after 12 weeks of supplementation. A significant decrease of the serum
      triglyceride level (P < 0.001), glucose, insulin, calculated IR HOMA (P < 0.05),
      and inflammatory markers (TNF-alpha, IL-6, and hs-CRP, P < 0.001) was observed
      after seed mixture treatment. The serum levels of CRP and TNF-alpha negative
      correlate with ALA, DHA, and DGLA. CONCLUSION: Results of this study indicated
      that dietary milled sesame/pumpkin/flax seed mixture added to a habitual diet
      lowered triglyceride and CRP, TNF-alpha, IL-6 levels, affect glycemic control and
      improved fatty acid profile and pruritus symptoms in hemodialysis patients.

PMID- 24578651
TI  - Rapid preparation of biosorbents with high ion exchange capacity from rice straw
      and bagasse for removal of heavy metals.
AB  - This work describes the preparation of the cellulose phosphate with high ion
      exchange capacity from rice straw and bagasse for removal of heavy metals. In
      this study, rice straw and bagasse were modified by the reaction with phosphoric
      acid in the presence of urea. The introduced phosphoric group is an ion
      exchangeable site for heavy metal ions. The reaction by microwave heating yielded
      modified rice straw and modified bagasse with greater ion exchange capacities
      (~3.62 meq/g) and shorter reaction time (1.5-5.0 min) than the phosphorylation by
      oil bath heating. Adsorption experiments towards Pb2+, Cd2+, and Cr3+ ions of the
      modified rice straw and the modified bagasse were performed at room temperature
      (heavy metal concentration 40 ppm, adsorbent 2.0 g/L). The kinetics of adsorption
      agreed with the pseudo-second-order model. It was shown that the modified rice
      straw and the modified bagasse could adsorb heavy metal ions faster than the
      commercial ion exchange resin (Dowax). As a result of Pb2+ sorption test, the
      modified rice straw (RH-NaOH 450W) removed Pb2+ much faster in the initial step
      and reached 92% removal after 20 min, while Dowax (commercial ion exchange resin)
      took 90 min for the same removal efficiency.

PMID- 24578652
TI  - Dynamic behavior of positive solutions for a leslie predator-prey system with
      mutual interference and feedback controls.
AB  - We consider a Leslie predator-prey system with mutual interference and feedback
      controls. For general nonautonomous case, by using differential inequality theory
      and constructing a suitable Lyapunov functional, we obtain some sufficient
      conditions which guarantee the permanence and the global attractivity of the
      system. For the periodic case, we obtain some sufficient conditions which
      guarantee the existence, uniqueness, and stability of a positive periodic
      solution. 

PMID- 24578653
TI  - Two mathematical models for generation of crowned tooth surface.
AB  - Gear couplings are mechanical components to connect shaft ends and eliminate the
      misalignments. The most important element of the gear coupling is the hub which
      is an external gear having crowned teeth. The crowned teeth on the hub are
      typically produced by hobbing. The resulting tooth surface depends on several
      parameters. It is influenced by the size of the hob and the feed. In this paper
      two mathematical models of the crowned tooth surface are introduced for the
      generation of the idealized tooth surfaces. These are the profile-shifting and
      the two-parameter enveloping methods. Our aim is to compare the obtained crowned
      tooth profiles for the two examined models and to investigate the results. From
      our numerical results, it was found that the two profiles show indistinguishable
      differences. 

PMID- 24578654
TI  - Synthesis, crystal structure, and thermal decomposition of the cobalt(II) complex
      with 2-picolinic acid.
AB  - The cobalt(II) complex of 2-picolinic acid (Hpic), namely, [Co(pic)2(H2O)2] .
      2H2O, was synthesized with the reaction of cobalt acetate and 2-picolinic acid as
      the reactants by solid-solid reaction at room temperature. The composition and
      structure of the complex were characterized by elemental analysis, infrared
      spectroscopy, single crystal X-ray diffraction, and thermogravimetry-differential
      scanning calorimetry (TG-DSC). The crystal structure of the complex belongs to
      monoclinic system and space group P2(1)/n, with cell parameters of a = 9.8468(7)
      A, b = 5.2013(4) A, c = 14.6041(15) A, beta = 111.745(6) degrees , V = 747.96(11)
      A3, Z = 2, D(c) = 1.666 g cm-3, R1 = 0.0297, and wR2 = 0.0831. In the title
      complex, the Co(II) ion is six-coordinated by two pyridine N atoms and two
      carboxyl O atoms from two 2-picolinic acid anions, and two O atoms from two H2O
      molecules, and forming a slightly distorted octahedral geometry. The thermal
      decomposition processes of the complex under nitrogen include dehydration and
      pyrolysis of the ligand, and the final residue is cobalt oxalate at about 450
      degrees C.

PMID- 24578655
TI  - Ignition and flame stabilization of a strut-jet RBCC combustor with small rocket
      exhaust.
AB  - A Rocket Based Combined Cycle combustor model is tested at a ground direct
      connected rig to investigate the flame holding characteristics with a small
      rocket exhaust using liquid kerosene. The total temperature and the Mach number
      of the vitiated air flow, at exit of the nozzle are 1505 K and 2.6, respectively.
      The rocket base is embedded in a fuel injecting strut and mounted in the center
      of the combustor. The wall of the combustor is flush, without any reward step or
      cavity, so the strut-jet is used to make sure of the flame stabilization of the
      second combustion. Mass flow rate of the kerosene and oxygen injected into the
      rocket is set to be a small value, below 10% of the total fuel when the
      equivalence ratio of the second combustion is 1. The experiment has generated two
      different kinds of rocket exhaust: fuel rich and pure oxygen. Experiment result
      has shown that, with a relative small total mass flow rate of the rocket, the
      fuel rich rocket plume is not suitable for ignition and flame stabilization,
      while an oxygen plume condition is suitable. Then the paper conducts a series of
      experiments to investigate the combustion characteristics under this oxygen pilot
      method and found that the flame stabilization characteristics are different at
      different combustion modes. 

PMID- 24578656
TI  - A cascaded approach for correcting ionospheric contamination with large amplitude
      in HF skywave radars.
AB  - Ionospheric phase perturbation with large amplitude causes broadening sea
      clutter's Bragg peaks to overlap each other; the performance of traditional
      decontamination methods about filtering Bragg peak is poor, which greatly limits
      the detection performance of HF skywave radars. In view of the ionospheric phase
      perturbation with large amplitude, this paper proposes a cascaded approach based
      on improved S-method to correct the ionospheric phase contamination. This
      approach consists of two correction steps. At the first step, a time-frequency
      distribution method based on improved S-method is adopted and an optimal
      detection method is designed to obtain a coarse ionospheric modulation estimation
      from the time-frequency distribution. At the second correction step, based on the
      phase gradient algorithm (PGA) is exploited to eliminate the residual
      contamination. Finally, use the measured data to verify the effectiveness of the
      method. Simulation results show the time-frequency resolution of this method is
      high and is not affected by the interference of the cross term; ionospheric phase
      perturbation with large amplitude can be corrected in low signal-to-noise (SNR);
      such a cascade correction method has a good effect. 

PMID- 24578657
TI  - Using evolutionary computation on GPS position correction.
AB  - More and more devices are equipped with global positioning system (GPS). However,
      those handheld devices with consumer-grade GPS receivers usually have low
      accuracy in positioning. A position correction algorithm is therefore useful in
      this case. In this paper, we proposed an evolutionary computation based technique
      to generate a correction function by two GPS receivers and a known reference
      location. Locating one GPS receiver on the known location and combining its
      longitude and latitude information and exact poisoning information, the proposed
      technique is capable of evolving a correction function by such. The proposed
      technique can be implemented and executed on handheld devices without hardware
      reconfiguration. Experiments are conducted to demonstrate performance of the
      proposed technique. Positioning error could be significantly reduced from the
      order of 10 m to the order of 1 m. 

PMID- 24578658
TI  - Microstructure and nonohmic properties of SnO2-Ta2O5-ZnO system doped with ZrO2.
AB  - The microstructure and nonohmic properties of SnO2-Ta2O5-ZnO varistor system
      doped with different amounts of ZrO2 (0-2.0 mol%) were investigated. The proposed
      samples were sintered at 1400 degrees C for 2 h with conventional ceramic
      processing method. By X-ray diffraction, SnO2 cassiterite phase was found in all
      the samples, and no extra phases were identified in the detection limit. The
      doping of ZrO2 would degrade the densification of the varistor ceramics but
      inhibit the growth of SnO2 grains. In the designed range, varistors with 1.0 mol%
      ZrO2 presented the maximum nonlinear exponent of 15.9 and lowest leakage current
      of 110  MUA/cm2, but the varistor voltage increased monotonously with the doping
      amount of ZrO2.

PMID- 24578659
TI  - Preparation of multiwalled carbon nanotubes/hydroxyl-terminated silicone oil
      fiber and its application to analysis of crude oils.
AB  - A simple and efficient method to analyze the volatile and semivolatile organic
      compounds in crude oils has been developed based on direct immersion solid-phase
      microextraction coupled to comprehensive two-dimensional gas chromatography/time
      of-flight mass spectrometry (DI-SPME-GC * GC/TOFMS). A novel fiber, multiwalled
      carbon nanotubes/hydroxyl-terminated silicone oil (MWNTs-TSO-OH), was prepared by
      sol-gel technology. Using standard solutions, the extraction conditions were
      optimized such as extraction mode, extraction temperature, extraction time, and
      salts effect. With the optimized conditions, a real crude oil sample was
      extracted and then analyzed in detail. It shows that the proposed method is very
      effective in simultaneously analyzing the normal and branched alkanes,
      cycloalkanes, aromatic hydrocarbons, and biomarkers of crude oil such as steranes
      and terpanes. Furthermore, the method showed good linearity (r > 0.999),
      precision (RSD < 8%), and detection limits ranging from 0.2 to 1.6 ng/L. 

PMID- 24578661
TI  - Geometric assortative growth model for small-world networks.
AB  - It has been shown that both humanly constructed and natural networks are often
      characterized by small-world phenomenon and assortative mixing. In this paper, we
      propose a geometrically growing model for small-world networks. The model
      displays both tunable small-world phenomenon and tunable assortativity. We obtain
      analytical solutions of relevant topological properties such as order, size,
      degree distribution, degree correlation, clustering, transitivity, and diameter.
      It is also worth noting that the model can be viewed as a generalization for an
      iterative construction of Farey graphs. 

PMID- 24578662
TI  - Approximate solution of time-fractional advection-dispersion equation via
      fractional variational iteration method.
AB  - This paper aims to obtain the approximate solution of time-fractional advection
      dispersion equation (FADE) involving Jumarie's modification of Riemann-Liouville
      derivative by the fractional variational iteration method (FVIM). FVIM provides
      an analytical approximate solution in the form of a convergent series. Some
      examples are given and the results indicate that the FVIM is of high accuracy,
      more efficient, and more convenient for solving time FADEs. 

PMID- 24578660
TI  - Duration of antimicrobial therapy in community acquired pneumonia: less is more.
AB  - Community acquired pneumonia (CAP) represents the most common cause of infection
      related morbidity and mortality worldwide. Appropriate treatment of CAP is
      challenging and sometimes limited by the availability to obtain rapid and timely
      identification of the etiologic agent in order to initiate or deescalate the
      correct antimicrobial therapy. As a consequence, prescribers frequently select
      empiric antimicrobial therapy using clinical judgment, local patterns of
      antimicrobial resistance, and, sometimes, individual patient expectations. These
      issues may contribute to prolonged courses of inappropriate therapy. In this
      review, we discuss the evidence and recommendations from international guidelines
      for the management of CAP and the clinical trials that specifically addressed
      duration of antimicrobial therapy for CAP in adults. In randomized controlled
      trials comparing the clinical efficacy of a short-course antimicrobial regimen
      versus an extended-course regimen, no differences in terms of clinical success,
      bacterial eradication, adverse events, and mortality were observed. The use of
      biomarkers, such as procalcitonin, to guide the initiation and duration of
      antimicrobial therapy may reduce total antibiotic exposure and treatment
      duration, healthcare costs, and the risk of developing antimicrobial resistance.
      In clinical practice, antimicrobial stewardship interventions may improve the
      management of CAP and may help in reducing treatment duration. Sometimes "less is
      more" in CAP. 

PMID- 24578663
TI  - Quantum key based burst confidentiality in optical burst switched networks.
AB  - The optical burst switching (OBS) is an emergent result to the technology concern
      that could achieve a feasible network in future. They are endowed with the
      ability to meet the bandwidth requirement of those applications that require
      intensive bandwidth. There are more domains opening up in the OBS that evidently
      shows their advantages and their capability to face the future network traffic.
      However, the concept of OBS is still far from perfection facing issues in case of
      security threat. The transfer of optical switching paradigm to optical burst
      switching faces serious downfall in the fields of burst aggregation, routing,
      authentication, dispute resolution, and quality of service (QoS). This paper
      deals with employing RC4 (stream cipher) to encrypt and decrypt bursts thereby
      ensuring the confidentiality of the burst. Although the use of AES algorithm has
      already been proposed for the same issue, by contrasting the two algorithms under
      the parameters of burst encryption and decryption time, end-to-end delay, it was
      found that RC4 provided better results. This paper looks to provide a better
      solution for the confidentiality of the burst in OBS networks. 

PMID- 24578664
TI  - Multifractal framework based on blanket method.
AB  - This paper proposes two local multifractal measures motivated by blanket method
      for calculation of fractal dimension. They cover both fractal approaches familiar
      in image processing. The first two measures (proposed Methods 1 and 3) support
      model of image with embedded dimension three, while the other supports model of
      image embedded in space of dimension three (proposed Method 2). While the
      classical blanket method provides only one value for an image (fractal dimension)
      multifractal spectrum obtained by any of the proposed measures gives a whole
      range of dimensional values. This means that proposed multifractal blanket model
      generalizes classical (monofractal) blanket method and other versions of this
      monofractal approach implemented locally. Proposed measures are validated on
      Brodatz image database through texture classification. All proposed methods give
      similar classification results, while average computation time of Method 3 is
      substantially longer. 

PMID- 24578665
TI  - Color temperature tunable white-light LED cluster with extrahigh color rendering
      index.
AB  - The correlated color temperature (CCT) tunable white-light LED cluster with
      extrahigh color rendering property has been found by simulation and fabricated,
      which consists of three WW LEDs (CCT = 3183 K), one red LED (634.1 nm), one green
      LED (513.9 nm), and one blue LED (456.2 nm). The experimental results show that
      this cluster can realize the CCT tunable white-lights with a color rendering
      index (CRI) above 93, special CRI R9 for strong red above 90, average value of
      the special CRIs of R9 to R12 for the four saturated colors (red, yellow, green,
      and blue) above 83, and luminous efficacies above 70 lm/W at CCTs of 2719 K to
      6497 K.

PMID- 24578666
TI  - A comprehensive estimation of the economic effects of meteorological services
      based on the input-output method.
AB  - Concentrating on consuming coefficient, partition coefficient, and Leontief
      inverse matrix, relevant concepts and algorithms are developed for estimating the
      impact of meteorological services including the associated (indirect, complete)
      economic effect. Subsequently, quantitative estimations are particularly obtained
      for the meteorological services in Jiangxi province by utilizing the input-output
      method. It is found that the economic effects are noticeably rescued by the
      preventive strategies developed from both the meteorological information and
      internal relevance (interdependency) in the industrial economic system. Another
      finding is that the ratio range of input in the complete economic effect on
      meteorological services is about 1 : 108.27-1 : 183.06, remarkably different from
      a previous estimation based on the Delphi method (1 : 30-1 : 51). Particularly,
      economic effects of meteorological services are higher for nontraditional users
      of manufacturing, wholesale and retail trades, services sector, tourism and
      culture, and art and lower for traditional users of agriculture, forestry,
      livestock, fishery, and construction industries. 

PMID- 24578667
TI  - Nonlinear earthquake analysis of reinforced concrete frames with fiber and
      Bernoulli-Euler beam-column element.
AB  - A beam-column element based on the Euler-Bernoulli beam theory is researched for
      nonlinear dynamic analysis of reinforced concrete (RC) structural element.
      Stiffness matrix of this element is obtained by using rigidity method. A solution
      technique that included nonlinear dynamic substructure procedure is developed for
      dynamic analyses of RC frames. A predicted-corrected form of the Bossak-alpha
      method is applied for dynamic integration scheme. A comparison of experimental
      data of a RC column element with numerical results, obtained from proposed
      solution technique, is studied for verification the numerical solutions.
      Furthermore, nonlinear cyclic analysis results of a portal reinforced concrete
      frame are achieved for comparing the proposed solution technique with Fibre
      element, based on flexibility method. However, seismic damage analyses of an 8
      story RC frame structure with soft-story are investigated for cases of
      lumped/distributed mass and load. Damage region, propagation, and intensities
      according to both approaches are researched.

PMID- 24578669
TI  - Impacts of nickel nanoparticles on mineral carbonation.
AB  - This work presents experimental results regarding the use of pure nickel
      nanoparticles (NiNP) as a mineral carbonation additive. The aim was to confirm if
      the catalytic effect of NiNP, which has been reported to increase the dissolution
      of CO2 and the dissociation of carbonic acid in water, is capable of accelerating
      mineral carbonation processes. The impacts of NiNP on the CO2 mineralization by
      four alkaline materials (pure CaO and MgO, and AOD and CC steelmaking slags), on
      the product mineralogy, on the particle size distribution, and on the morphology
      of resulting materials were investigated. NiNP-containing solution was found to
      reach more acidic pH values upon CO2 bubbling, confirming a higher quantity of
      bicarbonate ions. This effect resulted in acceleration of mineral carbonation in
      the first fifteen minutes of reaction time when NiNP was present. After this
      initial stage, however, no benefit of NiNP addition was seen, resulting in very
      similar carbonation extents after one hour of reaction time. It was also found
      that increasing solids content decreased the benefit of NiNP, even in the early
      stages. These results suggest that NiNP has little contribution to mineral
      carbonation processes when the dissolution of alkaline earth metals is rate
      limiting.

PMID- 24578668
TI  - An overview of the environmental applicability of vermicompost: from wastewater
      treatment to the development of sensitive analytical methods.
AB  - The use of vermicompost (humified material) for treating wastewaters, remediating
      polluted soils, improving agricultural productivity, protecting crop production,
      and developing sensitive analytical methods is reviewed here, covering the past
      17 years. The main advantages of vermicompost, considering all applications
      covered in this paper, comprise (i) easy acquisition, (ii) low costs, (iii)
      structural, chemical, and biological characteristics responsible for exceptional
      adsorptive capacities as well as pollutant degradation, and (iv) the promotion of
      biocontrol. Specifically, for wastewater decontamination, a considerable number
      of works have verified the adsorption of toxic metals, but the application of
      vermicompost is still scarce for the retention of organic compounds. Problems
      related to the final disposal of enriched vermicompost (after treatment steps)
      are often found, in spite of some successful destinations such as organic
      fertilizer. For decontaminating soils, the use of vermicompost is quite scarce,
      mainly for inorganic pollutants. In agricultural productivity and biocontrol,
      vermicompost imparts remarkable benefits regarding soil aggregation, plant
      nutrition, and the development of beneficial microorganisms against
      phytopathogens. Finally, the use of vermicompost in sensitive analytical methods
      for quantifying toxic metals is the newest application of this adsorbent. 

PMID- 24578670
TI  - UV-C radiation as a factor reducing microbiological contamination of fish meal.
AB  - Fish meals, added to feeds as a source of protein, may contain pathogenic
      bacteria. Therefore, effective methods for their sanitizing, such as UV-C
      radiation, are needed to minimize the epidemiological risk. The objective of this
      study was to evaluate the effect of UV-C radiation on the sanitary state of fish
      meals. The research materials included salmon and cod meals. Samples of the fish
      meals were inoculated with suspensions of Salmonella, E. coli, enterococci, and
      C. sporogenes spores and exposed to the following surface UV-C fluencies: 0-400
      J.m-2 for bacteria and 0-5000 J.m-2 for spores. For the vegetative forms, the
      highest theoretical lethal UV-C dose, ranging from 670.99 to 688.36 J.m-2
      depending on the meal type, was determined for Salmonella. The lowest UV-C
      fluency of 363.34-363.95 J.m-2 was needed for the inactivation of Enterococcus
      spp. Spores were considerably more resistant, and the UV-C doses necessary for
      inactivation were 159571.1 J.m-2 in salmon meal and 66836.9 J.m-2 in cod meal.
      The application of UV-C radiation for the sanitization of fish meals proved to be
      a relatively effective method for vegetative forms of bacteria but was
      practically ineffective for spores.

PMID- 24578671
TI  - Multisynchronization of chaotic oscillators via nonlinear observer approach.
AB  - The goal of this work is to synchronize a class of chaotic oscillators in a
      master-slave scheme, under different initial conditions, considering several
      slaves systems. The Chen oscillator is employed as a benchmark model and a
      nonlinear observer is proposed to reach synchronicity between the master and the
      slaves' oscillators. The proposed observer contains a proportional and integral
      form of a bounded function of the synchronization error in order to provide
      asymptotic synchronization with a satisfactory performance. Numerical experiments
      were carried out to show the operation of the considered methodology. 

PMID- 24578672
TI  - How to develop renewable power in China? A cost-effective perspective.
AB  - To address the problems of climate change and energy security, Chinese government
      strived to develop renewable power as an important alternative of conventional
      electricity. In this paper, the learning curve model is employed to describe the
      decreasing unit investment cost due to accumulated installed capacity; the
      technology diffusion model is used to analyze the potential of renewable power.
      Combined with the investment cost, the technology potential, and scenario
      analysis of China social development in the future, we develop the Renewable
      Power Optimization Model (RPOM) to analyze the optimal development paths of three
      sources of renewable power from 2009 to 2020 in a cost-effective way. Results
      show that (1) the optimal accumulated installed capacities of wind power, solar
      power, and biomass power will reach 169000, 20000, and 30000 MW in 2020; (2) the
      developments of renewable power show the intermittent feature; (3) the unit
      investment costs of wind power, solar power, and biomass power will be 4500,
      11500, and 5700 Yuan/KW in 2020; (4) the discounting effect dominates the
      learning curve effect for solar and biomass powers; (5) the rise of on-grid ratio
      of renewable power will first promote the development of wind power and then
      solar power and biomass power. 

PMID- 24578673
TI  - Assessment of renewable energy technology and a case of sustainable energy in
      mobile telecommunication sector.
AB  - The rapid growth of the mobile telecommunication sectors of many emerging
      countries creates a number of problems such as network congestion and poor
      service delivery for network operators. This results primarily from the lack of a
      reliable and cost-effective power solution within such regions. This study
      presents a comprehensive review of the underlying principles of the renewable
      energy technology (RET) with the objective of ensuring a reliable and cost
      effective energy solution for a sustainable development in the emerging world.
      The grid-connected hybrid renewable energy system incorporating a power
      conversion and battery storage unit has been proposed based on the availability,
      dynamism, and technoeconomic viability of energy resources within the region. The
      proposed system's performance validation applied a simulation model developed in
      MATLAB, using a practical load data for different locations with varying climatic
      conditions in Nigeria. Results indicate that, apart from being environmentally
      friendly, the increase in the overall energy throughput of about 4 kWh/$ of the
      proposed system would not only improve the quality of mobile services, by making
      the operations of GSM base stations more reliable and cost effective, but also
      better the living standards of the host communities.

PMID- 24578674
TI  - Optimal sharpening of compensated comb decimation filters: analysis and design.
AB  - Comb filters are a class of low-complexity filters especially useful for
      multistage decimation processes. However, the magnitude response of comb filters
      presents a droop in the passband region and low stopband attenuation, which is
      undesirable in many applications. In this work, it is shown that, for stringent
      magnitude specifications, sharpening compensated comb filters requires a lower
      degree sharpening polynomial compared to sharpening comb filters without
      compensation, resulting in a solution with lower computational complexity. Using
      a simple three-addition compensator and an optimization-based derivation of
      sharpening polynomials, we introduce an effective low-complexity filtering
      scheme. Design examples are presented in order to show the performance
      improvement in terms of passband distortion and selectivity compared to other
      methods based on the traditional Kaiser-Hamming sharpening and the Chebyshev
      sharpening techniques recently introduced in the literature. 

PMID- 24578675
TI  - Rapid mass spectrometric analysis of a novel fucoidan, extracted from the brown
      alga Coccophora langsdorfii.
AB  - The novel highly sulfated (35%) fucoidan fraction Cf2 , which contained, along
      with fucose, galactose and traces of xylose and uronic acids was purified from
      the brown alga Coccophora langsdorfii. Its structural features were predominantly
      determined (in comparison with fragments of known structure) by a rapid mass
      spectrometric investigation of the low-molecular-weight fragments, obtained by
      "mild" (5 mg/mL) and "exhaustive" (maximal concentration) autohydrolysis. Tandem
      matrix-assisted laser desorption/ionization mass spectra (MALDI-TOF/TOFMS) of
      fucooligosaccharides with even degree of polymerization (DP), obtained by "mild"
      autohydrolysis, were the same as that observed for fucoidan from Fucus
      evanescens, which have a backbone of alternating (1 -> 3)- and (1 -> 4) linked
      sulfated at C-2 and sometimes at C-4 of 3-linked alpha -L-Fucp residues.
      Fragmentation patterns of oligosaccharides with odd DP indicated sulfation at C-2
      and at C-4 of (1 -> 3) linked alpha -L-Fucp residues on the reducing terminus.
      Minor sulfation at C-3 was also suggested. The "exhaustive" autohydrolysis
      allowed us to observe the "mixed" oligosaccharides, built up of fucose/xylose and
      fucose/galactose. Xylose residues were found to occupy both the reducing and
      nonreducing termini of FucXyl disaccharides. Nonreducing galactose residues as
      part of GalFuc disaccharides were found to be linked, possibly, by 2-type of
      linkage to fucose residues and were found to be sulfated, most likely, at
      position C-2. 

PMID- 24578676
TI  - Visible light and/or UVA offer a strong amplification of the anti-tumor effect of
      curcumin.
AB  - Curcumin, a dietary pigment from the plant Curcuma longa, inhibits cell
      proliferation and induces apoptosis in different cell lines. The therapeutic
      benefit is hampered by a very low absorption after trans-dermal or oral
      application. Therefore, great efforts were undertaken to enhance the
      effectiveness of curcumin. Recently, it was demonstrated that curcumin offers the
      described effects also at low concentrations (0.2-1 MUg/ml) when applied in
      combination with UVA or visible light. The efficacy of this combination was shown
      in human epidermal keratinocytes and in a panel of other cell species in vitro as
      well as in a xenograft tumor model with A431 tumor cells injected subcutaneously
      in the flanks of NMRI nude mice in vivo. The treatment of keratinocytes with
      curcumin and light resulted in the inhibition of cell growth, and in the
      induction of apoptosis, whereas no toxic cell membrane damage was detectable. The
      treatment of tumor bearing nude mice with curcumin and visible light resulted in
      reduced tumor volumes, reduced proliferation rates, and the induction of
      apoptosis in the tumors. On the molecular level inhibition of extracellular
      regulated kinases 1/2 and epidermal growth factor receptor was observed which may
      aid to inhibition of proliferation and induction of apoptosis. This review covers
      the experiences of the new combination treatment of human tumors.

PMID- 24578677
TI  - Pleuroparenchymal Fibroelastosis: Its Clinical Characteristics.
AB  - Pleuroparenchymal fibroelastosis (PPFE) is a rare pulmonary fibrosis that is
      clinically characterized by upperlobe predominant fibrosis. PPFE is a slowly
      progressive disorder and its first symptom is dyspnea or dry cough. Chest pain
      because of pneumothorax may be the first symptom in some patients. Patients with
      PPFE are slender with a flat rib cage or abnormally narrowed anterior-posterior
      thoracic dimension. Decreases in forced vital capacity, total lung capacity, and
      diffusing capacity are respiratory-function characteristics of PPFE, similar to
      those seen in idiopathic pulmonary fibrosis (IPF). The most remarkable difference
      in clinical features between PPFE and IPF is imaging findings, with upper-lobe
      predominant lesions in PPFE and lower-lobe-predominant lesions in IPF.

PMID- 24578678
TI  - Regulation of Stem Cell Fate in a Three-Dimensional Micropatterned Dual
      Crosslinked Hydrogel System.
AB  - Micropatterning technology is a powerful tool for controlling the cellular
      microenvironment and investigating the effects of physical parameters on cell
      behaviors, such as migration, proliferation, apoptosis, and differentiation.
      Although there have been significant developments in regulating the spatial and
      temporal distribution of physical properties in various materials, little is
      known about the role of the size of micropatterned regions of hydrogels with
      different crosslinking densities on the response of encapsulated cells. In this
      study, novel alginate hydrogel system is engineered that can be micropatterned
      three-dimensionally to create regions that are crosslinked by a single mechanism
      or dual mechanisms. By manipulating micropattern size while keeping the overall
      ratio of single- to dual-crosslinked hydrogel volume constant, the physical
      properties of the micropatterned alginate hydrogels are spatially tunable. When
      human adipose-derived stem cells (hASCs) are photoencapsulated within
      micropatterned hydrogels, their proliferation rate is a function of micropattern
      size. Additionally, micropattern size dictates the extent of osteogenic and
      chondrogenic differentiation of photoencapsulated hASC. The size of 3D
      micropatterned physical properties in this new hydrogel system introduces a new
      design parameter for regulating various cellular behaviors, and this dual
      crosslinked hydrogel system provides a new platform for studying proliferation
      and differentiation of stem cells in a spatially controlled manner for tissue
      engineering and regenerative medicine applications.

PMID- 24578679
TI  - Composite three-dimensional woven scaffolds with interpenetrating network
      hydrogels to create functional synthetic articular cartilage.
AB  - The development of synthetic biomaterials that possess mechanical properties that
      mimic those of native tissues remains an important challenge to the field of
      materials. In particular, articular cartilage is a complex nonlinear,
      viscoelastic, and anisotropic material that exhibits a very low coefficient of
      friction, allowing it to withstand millions of cycles of joint loading over
      decades of wear. Here we show that a three-dimensionally woven fiber scaffold
      that is infiltrated with an interpenetrating network hydrogel can provide a
      functional biomaterial that provides the load-bearing and tribological properties
      of native cartilage. An interpenetrating dual-network "tough-gel" consisting of
      alginate and polyacrylamide was infused into a porous three-dimensionally woven
      poly(epsilon-caprolactone) fiber scaffold, providing a versatile fiber-reinforced
      composite structure as a potential acellular or cell-based replacement for
      cartilage repair.

PMID- 24578680
TI  - Therapeutic intraspinal stimulation to generate activity and promote long-term
      recovery.
AB  - Neuroprosthetic approaches have tremendous potential for the treatment of
      injuries to the brain and spinal cord by inducing appropriate neural activity in
      otherwise disordered circuits. Substantial work has demonstrated that stimulation
      applied to both the central and peripheral nervous system leads to immediate and
      in some cases sustained benefits after injury. Here we focus on cervical
      intraspinal microstimulation (ISMS) as a promising method of activating the
      spinal cord distal to an injury site, either to directly produce movements or
      more intriguingly to improve subsequent volitional control of the paretic
      extremities. Incomplete injuries to the spinal cord are the most commonly
      observed in human patients, and these injuries spare neural tissue bypassing the
      lesion that could be influenced by neural devices to promote recovery of
      function. In fact, recent results have demonstrated that therapeutic ISMS leads
      to modest but sustained improvements in forelimb function after an incomplete
      spinal cord injury (SCI). This therapeutic spinal stimulation may promote long
      term recovery of function by providing the necessary electrical activity needed
      for neuron survival, axon growth, and synaptic stability. 

PMID- 24578681
TI  - Cell cycle activity of neural precursors in the diseased mammalian brain.
AB  - Basic research during embryonic development has led to the identification of
      general principles governing cell cycle progression, proliferation and
      differentiation of mammalian neural stem cells (NSC). These findings were
      recently translated to the adult brain in an attempt to identify the overall
      principles governing stemness in the two contexts and allowing us to manipulate
      the expansion of NSC for regenerative therapies. However, and despite a huge
      literature on embryonic neural precursors, very little is known about cell cycle
      parameters of adult neural, or any other somatic, stem cell. In this review, we
      briefly discuss the long journey of NSC research from embryonic development to
      adult homeostasis, aging and therapy with a specific focus on their quiescence
      and cell cycle length in physiological conditions and neurological disorders.
      Particular attention is given to a new important player in the field,
      oligodendrocyte progenitors, while discussing the limitation hampering further
      development in this challenging area. 

PMID- 24578683
TI  - Modulation of subventricular zone oligodendrogenesis: a role for hemopressin?
AB  - Neural stem cells (NSCs) from the subventricular zone (SVZ) have been indicated
      as a source of new oligodendrocytes to use in regenerative medicine for myelin
      pathologies. Indeed, NSCs are multipotent cells that can self-renew and
      differentiate into all neural cell types of the central nervous system. In normal
      conditions, SVZ cells are poorly oligodendrogenic, nevertheless their
      oligodendrogenic potential is boosted following demyelination. Importantly,
      progressive restriction into the oligodendrocyte fate is specified by extrinsic
      and intrinsic factors, endocannabinoids being one of these factors. Although a
      role for endocannabinoids in oligodendrogenesis has already been foreseen,
      selective agonists and antagonists of cannabinoids receptors produce severe
      adverse side effects. Herein, we show that hemopressin (Hp), a modulator of CB1
      receptors, increased oligodendroglial differentiation in SVZ neural
      stem/progenitor cell cultures derived from neonatal mice. The original results
      presented in this work suggest that Hp and derivates may be of potential interest
      for the development of future strategies to treat demyelinating diseases. 

PMID- 24578682
TI  - The mechanisms and treatment of asphyxial encephalopathy.
AB  - Acute post-asphyxial encephalopathy occurring around the time of birth remains a
      major cause of death and disability. The recent seminal insight that allows
      active neuroprotective treatment is that even after profound asphyxia (the
      "primary" phase), many brain cells show initial recovery from the insult during a
      short "latent" phase, typically lasting approximately 6 h, only to die hours to
      days later after a "secondary" deterioration characterized by seizures, cytotoxic
      edema, and progressive failure of cerebral oxidative metabolism. Although many of
      these secondary processes are potentially injurious, they appear to be primarily
      epiphenomena of the "execution" phase of cell death. Animal and human studies
      designed around this conceptual framework have shown that moderate cerebral
      hypothermia initiated as early as possible but before the onset of secondary
      deterioration, and continued for a sufficient duration to allow the secondary
      deterioration to resolve, has been associated with potent, long-lasting
      neuroprotection. Recent clinical trials show that while therapeutic hypothermia
      significantly reduces morbidity and mortality, many babies still die or survive
      with disabilities. The challenge for the future is to find ways of improving the
      effectiveness of treatment. In this review, we will dissect the known mechanisms
      of hypoxic-ischemic brain injury in relation to the known effects of hypothermic
      neuroprotection. 

PMID- 24578684
TI  - How age and linguistic competence alter the interplay of perceptual and cognitive
      factors when listening to conversations in a noisy environment.
AB  - Multi-talker conversations challenge the perceptual and cognitive capabilities of
      older adults and those listening in their second language (L2). In older adults
      these difficulties could reflect declines in the auditory, cognitive, or
      linguistic processes supporting speech comprehension. The tendency of L2
      listeners to invoke some of the semantic and syntactic processes from their first
      language (L1) may interfere with speech comprehension in L2. These challenges
      might also force them to reorganize the ways in which they perceive and process
      speech, thereby altering the balance between the contributions of bottom-up vs.
      top-down processes to speech comprehension. Younger and older L1s as well as
      young L2s listened to conversations played against a babble background, with or
      without spatial separation between the talkers and masker, when the spatial
      positions of the stimuli were specified either by loudspeaker placements (real
      location), or through use of the precedence effect (virtual location). After
      listening to a conversation, the participants were asked to answer questions
      regarding its content. Individual hearing differences were compensated for by
      creating the same degree of difficulty in identifying individual words in babble.
      Once compensation was applied, the number of questions correctly answered
      increased when a real or virtual spatial separation was introduced between babble
      and talkers. There was no evidence that performance differed between real and
      virtual locations. The contribution of vocabulary knowledge to dialog
      comprehension was found to be larger in the virtual conditions than in the real
      whereas the contribution of reading comprehension skill did not depend on the
      listening environment but rather differed as a function of age and language
      proficiency. The results indicate that the acoustic scene and the cognitive and
      linguistic competencies of listeners modulate how and when top-down resources are
      engaged in aid of speech comprehension. 

PMID- 24578686
TI  - Unsupervised learning of facial emotion decoding skills.
AB  - Research on the mechanisms underlying human facial emotion recognition has long
      focussed on genetically determined neural algorithms and often neglected the
      question of how these algorithms might be tuned by social learning. Here we show
      that facial emotion decoding skills can be significantly and sustainably improved
      by practice without an external teaching signal. Participants saw video clips of
      dynamic facial expressions of five different women and were asked to decide which
      of four possible emotions (anger, disgust, fear, and sadness) was shown in each
      clip. Although no external information about the correctness of the participant's
      response or the sender's true affective state was provided, participants showed a
      significant increase of facial emotion recognition accuracy both within and
      across two training sessions two days to several weeks apart. We discuss several
      similarities and differences between the unsupervised improvement of facial
      decoding skills observed in the current study, unsupervised perceptual learning
      of simple stimuli described in previous studies and practice effects often
      observed in cognitive tasks. 

PMID- 24578687
TI  - Reconstructing functional brain networks: have we got the basics right?

PMID- 24578685
TI  - Balance within the Neurexin Trans-Synaptic Connexus Stabilizes Behavioral
      Control.
AB  - Autism spectrum disorder (ASD) is characterized by a broad spectrum of behavioral
      deficits of unknown etiology. ASD associated mutations implicate numerous
      neurological pathways including a common association with the neurexin trans
      synaptic connexus (NTSC) which regulates neuronal cell-adhesion, neuronal
      circuitry, and neurotransmission. Comparable DNA lesions affecting the NTSC,
      however, associate with a diversity of behavioral deficits within and without the
      autism spectrum including a very strong association with Tourette syndrome. The
      NTSC is comprised of numerous post-synaptic ligands competing for trans-synaptic
      connection with one of the many different neurexin receptors yet no apparent
      association exists between specific NTSC molecules/complexes and specific
      behavioral deficits. Together these findings indicate a fundamental role for NTSC
      balance in stabilizing pre-behavioral control. Further molecular and clinical
      characterization and stratification of ASD and TS on the basis of NTSC status
      will help elucidate the molecular basis of behavior - and define how the NTSC
      functions in combination with other molecular determinates to strengthen
      behavioral control and specify behavioral deficits. 

PMID- 24578689
TI  - Hierarchical processing in Balint's syndrome: a failure of flexible top-down
      attention.
AB  - Patients with Balint' s syndrome are typically impaired at perceiving multiple
      objects simultaneously, and at evaluating the relationship between multiple
      objects in a scene (simultanagnosia). These deficits may not only be observed in
      complex scenes, but also when local elements of individual objects must be
      integrated into a perceptual global whole. Thus, unlike normal observers,
      patients with simultanagnosia typically show a bias towards the local forms, even
      to the extent that they cannot identify the global stimuli. However, we have
      previously shown that global processing is still attainable in Balint patients in
      certain scenarios (e.g., when local elements are unfamiliar). This suggests that
      in addition to a possible perceptual deficit that favors the local elements in
      these patients, impaired attentional control may be at the core of their unique
      performance. To test this hypothesis we manipulated the perceptual saliency of
      the local and global elements in a compound letter task so that it included
      global-more-salient or local-more-salient displays. We show that a Balint patient
      was able to accurately identify both global and local targets as long as they
      were the salient aspect of the compound letter. However, substantial impairment
      was evident when either the global or local elements were the less salient aspect
      of the compound letter. We conclude that in Balint' s syndrome there is a failure
      of flexible top-down attention both in biasing attention away from salient
      irrelevant aspects of the display (salience-based-selection) and in impaired
      disengagement from irrelevant but salient items once they have been selected. 

PMID- 24578688
TI  - Hippocampal Sclerosis Affects fMR-Adaptation of Lyrics and Melodies in Songs.
AB  - Songs constitute a natural combination of lyrics and melodies, but it is unclear
      whether and how these two song components are integrated during the emergence of
      a memory trace. Network theories of memory suggest a prominent role of the
      hippocampus, together with unimodal sensory areas, in the build-up of conjunctive
      representations. The present study tested the modulatory influence of the
      hippocampus on neural adaptation to songs in lateral temporal areas. Patients
      with unilateral hippocampal sclerosis and healthy matched controls were presented
      with blocks of short songs in which lyrics and/or melodies were varied or
      repeated in a crossed factorial design. Neural adaptation effects were taken as
      correlates of incidental emergent memory traces. We hypothesized that hippocampal
      lesions, particularly in the left hemisphere, would weaken adaptation effects,
      especially the integration of lyrics and melodies. Results revealed that lateral
      temporal lobe regions showed weaker adaptation to repeated lyrics as well as a
      reduced interaction of the adaptation effects for lyrics and melodies in patients
      with left hippocampal sclerosis. This suggests a deficient build-up of a sensory
      memory trace for lyrics and a reduced integration of lyrics with melodies,
      compared to healthy controls. Patients with right hippocampal sclerosis showed a
      similar profile of results although the effects did not reach significance in
      this population. We highlight the finding that the integrated representation of
      lyrics and melodies typically shown in healthy participants is likely tied to the
      integrity of the left medial temporal lobe. This novel finding provides the first
      neuroimaging evidence for the role of the hippocampus during repetitive exposure
      to lyrics and melodies and their integration into a song. 

PMID- 24578690
TI  - Time models and cognitive processes: a review.
AB  - The sense of time is an essential capacity of humans, with a major role in many
      of the cognitive processes expressed in our daily lifes. So far, in cognitive
      science and robotics research, mental capacities have been investigated in a
      theoretical and modeling framework that largely neglects the flow of time. Only
      recently there has been a rather limited, but constantly increasing interest in
      the temporal aspects of cognition, integrating time into a range of different
      models of perceptuo-motor capacities. The current paper aims to review existing
      works in the field and suggest directions for fruitful future work. This is
      particularly important for the newly developed field of artificial temporal
      cognition that is expected to significantly contribute in the development of
      sophisticated artificial agents seamlessly integrated into human societies. 

PMID- 24578691
TI  - Cognitive decline due to excess synaptic Zn(2+) signaling in the hippocampus.
AB  - Zinc is an essential component of physiological brain function. Vesicular zinc is
      released from glutamatergic (zincergic) neuron terminals and serves as a signal
      factor (Zn(2) (+) signal) in both the intracellular (cytosol) compartment and the
      extracellular compartment. Synaptic Zn(2) (+) signaling is dynamically linked to
      neurotransmission and is involved in processes of synaptic plasticity such as
      long-term potentiation and cognitive activity. On the other hand, the activity of
      the hypothalamic-pituitary-adrenal (HPA) axis, i.e., glucocorticoid secretion,
      which can potentiate glutamatergic neuron activity, is linked to cognitive
      function. HPA axis activity modifies synaptic Zn(2) (+) dynamics at zincergic
      synapses. An increase in HPA axis activity, which occurs after exposure to
      stress, may induce excess intracellular Zn(2) (+) signaling in the hippocampus,
      followed by hippocampus-dependent memory deficit. Excessive excitation of
      zincergic neurons in the hippocampus can contribute to cognitive decline under
      stressful and/or pathological conditions. This paper provides an overview of the
      ''Hypothesis and Theory'' of Zn(2) (+)-mediated modification of cognitive
      activity. 

PMID- 24578693
TI  - Influence of intranasal and carotid cooling on cerebral temperature balance and
      oxygenation.
AB  - The present study evaluated the influence of intranasal cooling with balloon
      catheters, increased nasal ventilation, or percutaneous cooling of the carotid
      arteries on cerebral temperature balance and oxygenation in six healthy male
      subjects. Aortic arch and internal jugular venous blood temperatures were
      measured to assess the cerebral heat balance and corresponding paired blood
      samples were obtained to evaluate cerebral metabolism and oxygenation at rest,
      following 60 min of intranasal cooling, 5 min of nasal ventilation, and 15 min
      with carotid cooling. Intranasal cooling induced a parallel drop in jugular
      venous and arterial blood temperatures by 0.30 +/- 0.08 degrees C (mean +/- SD),
      whereas nasal ventilation and carotid cooling failed to lower the jugular venous
      blood temperature. The magnitude of the arterio-venous temperature difference
      across the brain remained unchanged at -0.33 +/- 0.05 degrees C following
      intranasal and carotid cooling, but increased to -0.44 +/- 0.11 degrees C (P <
      0.05) following nasal ventilation. Calculated cerebral capillary oxygen tension
      was 43 +/- 3 mmHg at rest and remained unchanged during intranasal and carotid
      cooling, but decreased to 38 +/- 2 mmHg (P < 0.05) following increased nasal
      ventilation. In conclusion, percutaneous cooling of the carotid arteries and
      intranasal cooling with balloon catheters are insufficient to influence cerebral
      oxygenation in normothermic subjects as the cooling rate is only 0.3 degrees C
      per hour and neither intranasal nor carotid cooling is capable of inducing
      selective brain cooling. 

PMID- 24578692
TI  - Monitoring training status with HR measures: do all roads lead to Rome?
AB  - Measures of resting, exercise, and recovery heart rate are receiving increasing
      interest for monitoring fatigue, fitness and endurance performance responses,
      which has direct implications for adjusting training load (1) daily during
      specific training blocks and (2) throughout the competitive season. However,
      these measures are still not widely implemented to monitor athletes' responses to
      training load, probably because of apparent contradictory findings in the
      literature. In this review I contend that most of the contradictory findings are
      related to methodological inconsistencies and/or misinterpretation of the data
      rather than to limitations of heart rate measures to accurately inform on
      training status. I also provide evidence that measures derived from 5-min (almost
      daily) recordings of resting (indices capturing beat-to-beat changes in heart
      rate, reflecting cardiac parasympathetic activity) and submaximal exercise (30-
      to 60-s average) heart rate are likely the most useful monitoring tools. For
      appropriate interpretation at the individual level, changes in a given measure
      should be interpreted by taking into account the error of measurement and the
      smallest important change of the measure, as well as the training context
      (training phase, load, and intensity distribution). The decision to use a given
      measure should be based upon the level of information that is required by the
      athlete, the marker's sensitivity to changes in training status and the practical
      constrains required for the measurements. However, measures of heart rate cannot
      inform on all aspects of wellness, fatigue, and performance, so their use in
      combination with daily training logs, psychometric questionnaires and non
      invasive, cost-effective performance tests such as a countermovement jump may
      offer a complete solution to monitor training status in athletes participating in
      aerobic-oriented sports. 

PMID- 24578696
TI  - Internet use and decision making in community-based older adults.
AB  - Use of the internet may provide tools and resources for better decision making,
      yet little is known about the association of internet use with decision making in
      older persons. We examined this relationship in 661 community-dwelling older
      persons without dementia from the Rush Memory and Aging Project, an ongoing
      longitudinal study of aging. Participants were asked to report if they had access
      to the internet and how frequently they used the internet and email. A 12-item
      instrument was used to assess financial and healthcare decision making using
      materials designed to approximate those used in real world settings. Items were
      summed to yield a total decision making score. Associations were tested via
      linear regression models adjusted for age, sex, race, education, and a measure of
      global cognitive function. Secondary models further adjusted for income,
      depression, loneliness, social networks, social support, chronic medical
      conditions, instrumental activities of daily living (IADLs), life space size, and
      health and financial literacy. Interaction terms were used to test for effect
      modification. Almost 70% of participants had access to the internet, and of those
      with access, 55% used the internet at least several times a week. Higher
      frequency of internet use was associated with better financial and healthcare
      decision making (beta = 0.11, p = 0.002). The association persisted in a fully
      adjusted model (beta = 0.08, p = 0.024). Interaction models indicated that higher
      frequency of internet use attenuated the relationships of older age, poorer
      cognitive function, and lower levels of health and financial literacy with poorer
      healthcare and financial decision making. These findings indicate that internet
      use is associated with better health and financial decision making in older
      persons. Future research is required to understand whether promoting the use of
      the internet can produce improvements in healthcare and financial decision
      making. 

PMID- 24578697
TI  - The effect of cognitive aging on implicit sequence learning and dual tasking.
AB  - We investigated the influence of attentional demands on sequence-specific
      learning by means of the serial reaction time task (Nissen and Bullemer, 1987) in
      young (age 18-25) and aged (age 55-75) adults. Participants had to respond as
      fast as possible to a stimulus presented in one of four horizontal locations by
      pressing a key corresponding to the spatial position of the stimulus. During the
      training phase sequential blocks were accompanied by (1) no secondary task
      (single), (2) a secondary tone counting task (dual tone), or (3) a secondary
      shape counting task (dual shape). Both secondary tasks were administered to
      investigate whether low and high interference tasks interact with implicit
      learning and age. The testing phase, under baseline single condition, was
      implemented to assess differences in sequence-specific learning between young and
      aged adults. Results indicate that (1) aged subjects show less sequence learning
      compared to young adults, (2) young participants show similar implicit learning
      effects under both single and dual task conditions when we account for explicit
      awareness, and (3) aged adults demonstrate reduced learning when the primary task
      is accompanied with a secondary task, even when explicit awareness is included as
      a covariate in the analysis. These findings point to implicit learning deficits
      under dual task conditions that can be related to cognitive aging, demonstrating
      the need for sufficient cognitive resources while performing a sequence learning
      task. 

PMID- 24578695
TI  - Cortico-amygdala coupling as a marker of early relapse risk in cocaine-addicted
      individuals.
AB  - Addiction to cocaine is a chronic condition characterized by high rates of early
      relapse. This study builds on efforts to identify neural markers of relapse risk
      by studying resting-state functional connectivity (rsFC) in neural circuits
      arising from the amygdala, a brain region implicated in relapse-related processes
      including craving and reactivity to stress following acute and protracted
      withdrawal from cocaine. Whole-brain resting-state functional magnetic resonance
      imaging connectivity (6 min) was assessed in 45 cocaine-addicted individuals and
      22 healthy controls. Cocaine-addicted individuals completed scans in the final
      week of a residential treatment episode. To approximate preclinical models of
      relapse-related circuitry, separate seeds were derived for the left and right
      basolateral (BLA) and corticomedial (CMA) amygdala. Participants also completed
      the Iowa Gambling Task, Wisconsin Card Sorting Test, Cocaine Craving
      Questionnaire, Obsessive-Compulsive Cocaine Use Scale and Personality Inventory.
      Relapse within the first 30 days post-treatment (n = 24) was associated with
      reduced rsFC between the left CMA and ventromedial prefrontal cortex/rostral
      anterior cingulate cortex (vmPFC/rACC) relative to cocaine-addicted individuals
      who remained abstinent (non-relapse, n = 21). Non-relapse participants evidenced
      reduced rsFC between the bilateral BLA and visual processing regions (lingual
      gyrus/cuneus) compared to controls and relapsed participants. Early relapse was
      associated with fewer years of education but unrelated to trait reactivity to
      stress, neurocognitive and clinical characteristics or cocaine use history.
      Findings suggest that rsFC within neural circuits implicated in preclinical
      models of relapse may provide a promising marker of relapse risk in cocaine
      addicted individuals. Future efforts to replicate the current findings and alter
      connectivity within these circuits may yield novel interventions and improve
      treatment outcomes. 

PMID- 24578699
TI  - The mean as a multilevel issue.

PMID- 24578698
TI  - Does anyone need help? Age and gender effects on children's ability to recognize
      need-of-help.
AB  - The exploratory study presented here examines children's ability to recognize
      another person's need-of-help. This social perception process necessarily
      precedes the decision to actively help others. Fifty-eight children aged between
      5 and 13 completed three experimental paradigms. They were asked to look at black
      and-white drawings and to indicate which ones showed somebody in need of help. A
      control task requiring children to differentiate between pictures of humans and
      birds measured general categorization abilities. This experimental design enabled
      us to consider confounding effects of children's developmental status and
      motivation and to distinguish them from specific need-of-help recognition
      abilities. As gender and age have been shown to influence social perception as
      well as helping behavior, we explored whether these factors also have an impact
      on need-of-help recognition. Children's response accuracies and response times
      (RTs) were analyzed. We observed clearly higher accuracy rates for younger girls
      compared to younger boys specifically in the need-of-help recognition tasks. For
      boys, an age-related performance improvement was found. Younger girls performed
      at a similarly high level as older girls and boys. No gender differences were
      observed for children aged over nine. This report provides first evidence that
      the developmental trajectory of children's ability to recognize another person's
      need-of-help differs for girls and boys. 

PMID- 24578694
TI  - Gap junction modulation and its implications for heart function.
AB  - Gap junction communication (GJC) mediated by connexins is critical for heart
      function. To gain insight into the causal relationship of molecular mechanisms of
      disease pathology, it is important to understand which mechanisms contribute to
      impairment of gap junctional communication. Here, we present an update on the
      known modulators of connexins, including various interaction partners, kinases,
      and signaling cascades. This gap junction network (GJN) can serve as a blueprint
      for data mining approaches exploring the growing number of publicly available
      data sets from experimental and clinical studies. 

PMID- 24578700
TI  - Lipids in Aspergillus flavus-maize interaction.
AB  - In some filamentous fungi, the pathways related to the oxidative stress and
      oxylipins production are involved both in the process of host-recognition and in
      the pathogenic phase. In fact, recent studies have shown that the production of
      oxylipins in filamentous fungi, yeasts and chromists is also related to the
      development of the organism itself and to mechanisms of communication with the
      host at the cellular level. The oxylipins, also produced by the host during
      defense reactions, are able to induce sporulation and to regulate the
      biosynthesis of mycotoxins in several pathogenic fungi. In A. flavus, the
      oxylipins play a crucial role as signals for regulating the biosynthesis of
      aflatoxins, the conidiogenesis and the formation of sclerotia. To investigate the
      involvement of an oxylipins based cross-talk into Z. mays and A. flavus
      interaction, we analyzed the oxylipins profile of the wild type strain and of
      three mutants of A. flavus that are deleted at the Aflox1 gene level also during
      maize kernel invasion. A lipidomic approach has been addressed through the use of
      LC-ToF-MS, followed by a statistical analysis of the principal components (PCA).
      The results showed the existence of a difference between the oxylipins profile
      generated by the WT and the mutants onto challenged maize. In relation to this,
      aflatoxin synthesis which is largely hampered in vitro, is intriguingly restored.
      These results highlight the important role of maize oxylipin in driving secondary
      metabolism in A. flavus. 

PMID- 24578702
TI  - DNA-based stable isotope probing coupled with cultivation methods implicates
      Methylophaga in hydrocarbon degradation.
AB  - Marine hydrocarbon-degrading bacteria perform a fundamental role in the oxidation
      and ultimate removal of crude oil and its petrochemical derivatives in coastal
      and open ocean environments. Those with an almost exclusive ability to utilize
      hydrocarbons as a sole carbon and energy source have been found confined to just
      a few genera. Here we used stable isotope probing (SIP), a valuable tool to link
      the phylogeny and function of targeted microbial groups, to investigate
      hydrocarbon-degrading bacteria in coastal North Carolina sea water (Beaufort
      Inlet, USA) with uniformly labeled [(13)C]n-hexadecane. The dominant sequences in
      clone libraries constructed from (13)C-enriched bacterial DNA (from n-hexadecane
      enrichments) were identified to belong to the genus Alcanivorax, with <=98%
      sequence identity to the closest type strain-thus representing a putative novel
      phylogenetic taxon within this genus. Unexpectedly, we also identified (13)C
      enriched sequences in heavy DNA fractions that were affiliated to the genus
      Methylophaga. This is a contentious group since, though some of its members have
      been proposed to degrade hydrocarbons, substantive evidence has not previously
      confirmed this. We used quantitative PCR primers targeting the 16S rRNA gene of
      the SIP-identified Alcanivorax and Methylophaga to determine their abundance in
      incubations amended with unlabeled n-hexadecane. Both showed substantial
      increases in gene copy number during the experiments. Subsequently, we isolated a
      strain representing the SIP-identified Methylophaga sequences (99.9% 16S rRNA
      gene sequence identity) and used it to show, for the first time, direct evidence
      of hydrocarbon degradation by a cultured Methylophaga sp. This study demonstrates
      the value of coupling SIP with cultivation methods to identify and expand on the
      known diversity of hydrocarbon-degrading bacteria in the marine environment. 

PMID- 24578703
TI  - Mining the resource of cross-presentation.

PMID- 24578701
TI  - Making recombinant proteins in filamentous fungi- are we expecting too much?
AB  - Hosts used for the production of recombinant proteins are typically high-protein
      secreting mutant strains that have been selected for a specific purpose, such as
      efficient production of cellulose-degrading enzymes. Somewhat surprisingly,
      sequencing of the genomes of a series of mutant strains of the cellulolytic
      Trichoderma reesei, widely used as an expression host for recombinant gene
      products, has shed very little light on the nature of changes that boost high
      level protein secretion. While it is generally agreed and shown that protein
      secretion in filamentous fungi occurs mainly through the hyphal tip, there is
      growing evidence that secretion of proteins also takes place in sub-apical
      regions. Attempts to increase correct folding and thereby the yields of
      heterologous proteins in fungal hosts by co-expression of cellular chaperones and
      foldases have resulted in variable success; underlying reasons have been explored
      mainly at the transcriptional level. The observed physiological changes in fungal
      strains experiencing increasing stress through protein overexpression under
      strong gene promoters also reflect the challenge the host organisms are
      experiencing. It is evident, that as with other eukaryotes, fungal endoplasmic
      reticulum is a highly dynamic structure. Considering the above, there is an
      emerging body of work exploring the use of weaker expression promoters to avoid
      undue stress. Filamentous fungi have been hailed as candidates for the production
      of pharmaceutically relevant proteins for therapeutic use. One of the biggest
      challenges in terms of fungally produced heterologous gene products is their mode
      of glycosylation; fungi lack the functionally important terminal sialylation of
      the glycans that occurs in mammalian cells. Finally, exploration of the metabolic
      pathways and fluxes together with the development of sophisticated fermentation
      protocols may result in new strategies to produce recombinant proteins in
      filamentous fungi. 

PMID- 24578705
TI  - Should Steroid Therapy Be Necessarily Needed for Autoimmune Pancreatitis Patients
      with Lesion Resected due to Misdiagnosed or Suspected Malignancy?
AB  - To explore whether steroid therapy should be needed for autoimmune pancreatitis
      patients after operation, eight AIP patients receiving operation were enrolled in
      this study from January 2007 to July 2013. All patients underwent liver function,
      CA19-9, and contrast-enhanced CT and/or MRI. Tests of IgG and IgG4 were performed
      in some patients. Tests of serum TB/DB, gamma -GT, and gamma -globulin were
      undergone during the perioperative period. Six cases receiving resection were
      pathologically confirmed as AIP patients and two were confirmed by intraoperative
      biopsy. For seven patients, TB/DB level was transiently elevated 1 day or 4 days
      after operation but dropped below preoperative levels or to normal levels 7 days
      after operation, and serum gamma -GT level presented a downward trend. Serum
      gamma -globulin level exhibited a downward trend among six AIP patients after
      resection, while an upward trend was found in another two AIP patients receiving
      internal drainage. Steroid therapy was not given to all six AIP patients until
      two of them showed new lines of evidence of residual or extrapancreatic AIP
      lesion after operation, while another two cases without resection received
      steroid medication. Steroid therapy might not be recommended unless there are new
      lines of evidence of residual extrapancreatic AIP lesions after resection. 

PMID- 24578706
TI  - Effects of ion-releasing tooth-coating material on demineralization of bovine
      tooth enamel.
AB  - We compared the effect of a novel ion-releasing tooth-coating material that
      contained S-PRG (surface-reaction type prereacted glass-ionomer) filler to that
      of non-S-PRG filler and nail varnish on the demineralization of bovine enamel
      subsurface lesions. The demineralization process of bovine enamel was examined
      using quantitative light-induced fluorescence (QLF) and electron probe
      microanalyzer (EPMA) measurement. Ion concentrations in demineralizing solution
      were measured using inductively coupled plasma atomic (ICP) emission spectrometry
      and an ion electrode. The nail varnish group and the non-S-PRG filler group
      showed linear demineralization. Although the nail varnish group and the non-S-PRG
      filler group showed linear demineralization, the S-PRG filler group did not.
      Further, plane-scanning by EPMA analysis in the S-PRG filler group showed no
      changes in Ca ion distribution, and F ions showed peak levels on the surface of
      enamel specimens. Most ions in the demineralizing solution were present at higher
      concentrations in the S-PRG filler group than in the other two groups. In
      conclusion, only the S-PRG filler-containing tooth-coating material released ions
      and inhibited demineralization around the coating. 

PMID- 24578704
TI  - Endosperm transfer cell-specific genes and proteins: structure, function and
      applications in biotechnology.
AB  - Endosperm transfer cells (ETC) are one of four main types of cells in endosperm.
      A characteristic feature of ETC is the presence of cell wall in-growths that
      create an enlarged plasma membrane surface area. This specialized cell structure
      is important for the specific function of ETC, which is to transfer nutrients
      from maternal vascular tissue to endosperm. ETC-specific genes are of particular
      interest to plant biotechnologists, who use genetic engineering to improve grain
      quality and yield characteristics of important field crops. The success of
      molecular biology-based approaches to manipulating ETC function is dependent on a
      thorough understanding of the functions of ETC-specific genes and ETC-specific
      promoters. The aim of this review is to summarize the existing data on structure
      and function of ETC-specific genes and their products. Potential applications of
      ETC-specific genes, and in particular their promoters for biotechnology will be
      discussed. 

PMID- 24578707
TI  - IVIVC from Long Acting Olanzapine Microspheres.
AB  - In this study, four PLGA microsphere formulations of Olanzapine were
      characterized on the basis of their in vitro behavior at 37 degrees C, using a
      dialysis based method, with the goal of obtaining an IVIVC. In vivo profiles were
      determined by deconvolution (Nelson-Wagner method) and using fractional AUC. The
      in vitro and in vivo release profiles exhibited the same rank order of drug
      release. Further, in vivo profiles obtained with both approaches were nearly
      superimposable, suggesting that fractional AUC could be used as an alternative to
      the Nelson-Wagner method. A comparison of drug release profiles for the four
      formulations revealed that the in vitro profile lagged slightly behind in vivo
      release, but the results were not statistically significant (P < 0.0001). Using
      the four formulations that exhibited different release rates, a Level A IVIVC was
      established using the deconvolution and fractional AUC approaches. A nearly 1 : 1
      correlation (R (2) > 0.96) between in vitro release and in vivo measurements
      confirmed the excellent relationship between in vitro drug release and the amount
      of drug absorbed in vivo. The results of this study suggest that proper selection
      of an in vitro method will greatly aid in establishing a Level A IVIVC for long
      acting injectables. 

PMID- 24578709
TI  - Obstetric outcome and significance of labour induction in a health resource poor
      setting.
AB  - Objectives. The aim of this study was to evaluate the methods, indications,
      outcome of induced labor and its significance in obstetric practice in the study
      area. Methods. This was a retrospective study of cases of induced labor at the
      Catholic Maternity Hospital in Ogoja, Cross-River State, Nigeria, between January
      1, 2002, and December 31, 2011. Data on the sociodemographic characteristics of
      the parturient, induction methods, indications for induction, outcomes and
      reasons for failed induction were abstracted from personal case files and the
      hospital's maternity/delivery register. The data were analyzed with SPSS15.0
      window version. Result. The induction rate in this study was 11.5%. Induction was
      successful in 75.9% of cases but failed in 24.1%. Misoprostol was the commonest
      induction method (78.2%). The commonest indication for induction was postdate
      pregnancy (45.8%). Failed induction was due to fetal distress, prolonged labor,
      cephalopelvic disproportion and cord prolapse. The induction-delivery interval
      was 12 +/- 3.6 hours. Conclusion. Induction of labor is a common obstetric
      procedure which is safe and beneficial in well-selected and properly monitored
      high risk pregnancies where the benefits of early delivery outweigh the risk of
      continuing the pregnancy. 

PMID- 24578710
TI  - Introducing single dose liposomal amphotericin B for the treatment of visceral
      leishmaniasis in rural bangladesh: feasibility and acceptance to patients and
      health staff.
AB  - Background. For the treatment of visceral leishmaniasis in Bangladesh, single
      dose liposomal amphotericin B (ambisome) is supposed to be the safest and most
      effective treatment. Specific needs for application and storage raise questions
      about feasibility of its implementation and acceptance by patients and health
      staff. Methods. The study was carried out in the most endemic district of
      Bangladesh. Study population includes patients treated with ambisome or
      miltefosine, hospital staff, and a director of the national visceral
      leishmaniasis program. Study methods include direct observation (subdistrict
      hospitals), open interviews (heath staff and program personnel), structured
      questionnaires, and focus group discussions (patients). Results.
      Politicalcommitment for ambisome is strong; the general hospital infrastructure
      favours implementation but further strengthening is required, particularly for
      drug storage below 25 degrees C (refrigerators), back-up energy (fuel for
      generators), and supplies for ambisome administration (like 5% dextrose
      solution). Ambisome created high satisfaction in patients and hospital staff,
      less adverse events, and less income loss for patients compared to miltefosine.
      Conclusions. High political commitment, general capacities of subdistrict
      hospitals, and high acceptability favour the implementation of ambisome treatment
      in Bangladesh. However, strengthening of the infrastructure and uninterrupted
      supplies of essential accessories is mandatory before introducing sLAB in
      Bangladesh. 

PMID- 24578708
TI  - Formation and regulation of mitochondrial membranes.
AB  - Mitochondrial membrane phospholipids are essential for the mitochondrial
      architecture, the activity of respiratory proteins, and the transport of proteins
      into the mitochondria. The accumulation of phospholipids within mitochondria
      depends on a coordinate synthesis, degradation, and trafficking of phospholipids
      between the endoplasmic reticulum (ER) and mitochondria as well as
      intramitochondrial lipid trafficking. Several studies highlight the contribution
      of dietary fatty acids to the remodeling of phospholipids and mitochondrial
      membrane homeostasis. Understanding the role of phospholipids in the
      mitochondrial membrane and their metabolism will shed light on the molecular
      mechanisms involved in the regulation of mitochondrial function and in the
      mitochondrial-related diseases. 

PMID- 24578713
TI  - Association between respiratory viruses and asthma exacerbations.

PMID- 24578712
TI  - Primary repair of symptomatic neonates with tetralogy of Fallot with or without
      pulmonary atresia.
AB  - Recently, surgical outcomes of repair of tetralogy of Fallot (TOF) have improved.
      For patients with TOF older than 3 months, primary repair has been advocated
      regardless of symptoms. However, a surgical approach to symptomatic TOF in
      neonates or very young infants remains elusive. Traditionally, there have been
      two surgical options for these patients: primary repair versus an initial
      aortopulmonary shunt followed by repair. Early primary repair provides several
      advantages, including avoidance of shunt-related complications, early relief of
      hypoxia, promotion of normal lung development, avoidance of ventricular
      hypertrophy and fibrosis, and psychological comfort to the family. Because of
      advances in cardiopulmonary bypass techniques and accumulated experience in
      neonatal cardiac surgery, primary repair in neonates with TOF has been performed
      with excellent early outcomes (early mortality<5%), which may be superior to the
      outcomes of aortopulmonary shunting. A remaining question regarding surgical
      options is whether shunts can preserve the pulmonary valve annulus for TOF
      neonates with pulmonary stenosis. Symptomatic neonates and older infants have
      different anatomies of right ventricular outflow tract (RVOT) obstructions, which
      in neonates are nearly always caused by a hypoplastic pulmonary valve annulus
      instead of infundibular obstruction. Therefore, a shunt is less likely to
      preserve the pulmonary valve annulus than is primary repair. Primary repair of
      TOF can be performed safely in most symptomatic neonates. Patients who have had
      primary repair should be closely followed up to evaluate the RVOT pathology and
      right ventricular function. 

PMID- 24578711
TI  - Channelopathies.
AB  - Channelopathies are a heterogeneous group of disorders resulting from the
      dysfunction of ion channels located in the membranes of all cells and many
      cellular organelles. These include diseases of the nervous system (e.g.,
      generalized epilepsy with febrile seizures plus, familial hemiplegic migraine,
      episodic ataxia, and hyperkalemic and hypokalemic periodic paralysis), the
      cardiovascular system (e.g., long QT syndrome, short QT syndrome, Brugada
      syndrome, and catecholaminergic polymorphic ventricular tachycardia), the
      respiratory system (e.g., cystic fibrosis), the endocrine system (e.g., neonatal
      diabetes mellitus, familial hyperinsulinemic hypoglycemia, thyrotoxic hypokalemic
      periodic paralysis, and familial hyperaldosteronism), the urinary system (e.g.,
      Bartter syndrome, nephrogenic diabetes insipidus, autosomal-dominant polycystic
      kidney disease, and hypomagnesemia with secondary hypocalcemia), and the immune
      system (e.g., myasthenia gravis, neuromyelitis optica, Isaac syndrome, and anti
      NMDA [N-methyl-D-aspartate] receptor encephalitis). The field of channelopathies
      is expanding rapidly, as is the utility of molecular-genetic and
      electrophysiological studies. This review provides a brief overview and update of
      channelopathies, with a focus on recent advances in the pathophysiological
      mechanisms that may help clinicians better understand, diagnose, and develop
      treatments for these diseases. 

PMID- 24578714
TI  - Prevalence of respiratory viral infection in children hospitalized for acute
      lower respiratory tract diseases, and association of rhinovirus and influenza
      virus with asthma exacerbations.
AB  - PURPOSE: In this study, we aimed to investigate the prevalence of year-round
      respiratory viral infection in children with lower respiratory tract infection
      (LRTI) and the relationship between respiratory viral infection and allergen
      sensitization in exacerbating asthma. METHODS: We investigated the sources for
      acute LRTIs in children admitted to our hospital from May 2010 to April 2011. The
      6 most common respiratory viruses were isolated from nasopharyngeal aspirate
      using multiplex reverse transcription-polymerase chain reaction in 309 children;
      respiratory syncytial virus (RSV), adenovirus (AV), parainfluenza virus (PIV),
      influenza virus (IFV), human metapneumovirus (hMPV), rhinovirus (RV). Atopic
      sensitization was defined if more than 1 serum specific Immunoglobulin E level
      measured using UniCAP (Pharmacia) was over 0.35 IU/mL. RESULTS: RSV was the most
      common pathogen of bronchiolitis in hospitalized children through the year. RV or
      IFV infection was more prevalent in asthma exacerbations compared to other LRTIs.
      AV and hMPV were more likely to cause pneumonia. RV and IFV were associated with
      asthma exacerbations in children with atopic sensitization, but not in nonatopic
      children. CONCLUSION: RV and IFV are associated with hospitalization for asthma
      exacerbation in children with atopic sensitization.

PMID- 24578715
TI  - The correlation of blood pressure with height and weight in Korean adolescents
      aged 10-19 years; The Korean National Health and Nutrition Examination Surveys
      (2009-2011).
AB  - PURPOSE: Height-specific blood pressure (BP) is the standard parameter used to
      diagnose childhood hypertension. However, there has been some argument that
      weight may be a better variable than height in the reference BP standards.
      Therefore, before assessing the BP status using the reference BP standards, a
      basic understanding of the fundamental association of weight and height with BP
      is required. METHODS: In the present study, we analyzed the correlation of BP
      with height and weight in Korean adolescents (age, 10-19 years), using data from
      the Korean National Health and Nutrition Examination Surveys (2009-2011).
      RESULTS: Systolic BP (SBP) was more closely correlated with weight than with
      height in the normal weight (body mass index [BMI], <=85th percentile) and
      overweight (BMI, >85th percentile) groups and in the normal waist circumference
      (WC, <=90th percentile) and high WC (>90th percentile) groups in both sexes.
      Diastolic BP (DBP) had a higher correlation with height than with weight in the
      normal weight and normal WC groups, whereas weight was more closely associated
      with DBP than height in the overweight and high WC groups in both boys and girls.
      CONCLUSION: In Korean adolescents, weight had a greater effect on SBP than height
      in both the normal weight and overweight groups. DBP was mainly affected by
      height in the normal weight group, whereas weight was the major determinant of
      DBP in the overweight group. Therefore, it may be necessary to consider weight in
      the establishment of reference BP standards.

PMID- 24578717
TI  - Identification of a novel mutation in the CHD7 gene in a patient with CHARGE
      syndrome.
AB  - CHARGE syndrome has been estimated to occur in 1:10,000 births worldwide and
      shows various clinical manifestations. It is a genetic disorder characterized by
      a specific and a recognizable pattern of anomalies. The major clinical features
      are ocular coloboma, heart malformations, atresia of the choanae, growth
      retardation, genital hypoplasia, and ear abnormalities. The chromodomain helicase
      DNA-binding protein 7 (CHD7) gene, located on chromosome 8q12.1, causes CHARGE
      syndrome. The CHD7 protein is an adenosine triphosphate (ATP)-dependent chromatin
      remodeling protein. A total of 67% of patients clinically diagnosed with CHARGE
      syndrome have CHD7 mutations. Five hundred twenty-eight pathogenic and unique
      CHD7 alterations have been identified so far. We describe a patient with a CHARGE
      syndrome diagnosis who carried a novel de novo mutation, a c.3896T>C (p.
      leu1299Pro) missense mutation, in the CHD7 gene. This finding will provide more
      information for genetic counseling and expand our understanding of the
      pathogenesis and development of CHARGE syndrome. 

PMID- 24578716
TI  - Kidney size estimation in Korean children with Technesium-99m dimercaptosuccinic
      acid scintigraphy.
AB  - PURPOSE: Renal size is an important indicator to determine adequate organ growth
      in children. The aim of this study was to estimate renal size with Technesium-99m
      dimercaptosuccinic acid (DMSA) scan and propose a simple formula for predicting
      renal length in normal Korean children. METHODS: This study included 346 children
      (148 boys and 198 girls; age range, 1 month to 17 years) in whom renal length was
      measured using the DMSA scan. Patients with anatomical renal abnormalities or
      acute pyelonephritis were excluded. Children were divided into two groups: 214
      children (61.8%) were less than a year old (group 1) and 132 (38.2%) were >=1
      year (group 2). RESULTS: Renal length was larger on the left side than the right
      side, and there was no significant gender-related difference in renal length. We
      propose the following formula for renal length based on the analysis of the 346
      children in our study: the formula was as follows: 4.682*age (month)(0.137), R(2)
      =0.780. In group 1, the formula was renal length (cm)=0.127*age (month)+5.144,
      R(2) =0.354, and in group 2, the formula was 0.334*age (year)+6.477, R(2) =0.829.
      CONCLUSION: It is difficult to establish simple formulae in infants (R(2)
      =0.354). Therefore, further studies including relevant variables are needed for
      this age group. We proposed formulae to estimate renal length in Korean children
      over 1 year of age by using the DMSA scan.

PMID- 24578718
TI  - A novel PRF1 gene mutation in a fatal neonate case with type 2 familial
      hemophagocytic lymphohistiocytosis.
AB  - Hemophagocytic lymphohistiocytosis (HLH) occurs in the primary form (genetic or
      familial) or secondary form (acquired). The familial form of HLH (FHL) is a
      potentially fatal autosomal recessive disorder that occurs because of
      constitutional defects in cell-mediated cytotoxicity. Here, we report a fatal
      neonatal case of type 2 FHL (FHL2) that involved a novel frameshift mutation.
      Clinically, the newborn presented with severe sepsis-like features and required
      mechanical ventilation and continuous venovenous hemodiafiltration. Flow
      cytometry analysis showed marked HLH and complete absence of intracytoplasmic
      perforin expression in cytotoxic cells; therefore, we performed molecular genetic
      analyses for PRF1 mutations, which showed that the patient had a compound
      heterozygous mutation in PRF1, that is, c.65delC (p.Pro22Argfs*2) and
      c.1090_1091delCT (p.Leu364Glufs*93). Clinical and genetic assessments for FHL are
      required for neonates with refractory fever and progressive multiple organ
      failure, particularly when there is no evidence of microbiological or metabolic
      cause. 

PMID- 24578719
TI  - Depressive symptoms, conduct problems, and risk for polysubstance use among
      adolescents: Results from US national surveys.
AB  - Polysubstance use in adolescence is a known precursor to chronic substance
      misuse. Identifying risk factors for polysubstance use is necessary to inform its
      prevention. The present study examined the association of elevated levels of
      multiple mental health symptoms with adolescents' engagement in polysubstance use
      (past month use of alcohol, cigarettes, and marijuana). In a US national sample
      of 8th, 10th, and 12th grade students from Monitoring the Future surveys, we
      estimated probability of polysubstance use associated with high levels of
      depressive symptoms, conduct problems, or both. Depressive symptoms and conduct
      problems, alone and particularly in combination, were associated with drastically
      elevated probability of polysubstance use. Adolescents with high levels of both
      depressive symptoms and conduct problems had the highest probability of
      polysubstance use. Among 8th and 10th graders, probability of polysubstance use
      associated with co-occurring mental health problems was significantly higher for
      girls than boys.

PMID- 24578721
TI  - Evolution- and structure-based computational strategy reveals the impact of
      deleterious missense mutations on MODY 2 (maturity-onset diabetes of the young,
      type 2).
AB  - Heterozygous mutations in the central glycolytic enzyme glucokinase (GCK) can
      result in an autosomal dominant inherited disease, namely maturity-onset diabetes
      of the young, type 2 (MODY 2). MODY 2 is characterised by early onset: it usually
      appears before 25 years of age and presents as a mild form of hyperglycaemia. In
      recent years, the number of known GCK mutations has markedly increased. As a
      result, interpreting which mutations cause a disease or confer susceptibility to
      a disease and characterising these deleterious mutations can be a difficult task
      in large-scale analyses and may be impossible when using a structural
      perspective. The laborious and time-consuming nature of the experimental analysis
      led us to attempt to develop a cost-effective computational pipeline for diabetic
      research that is based on the fundamentals of protein biophysics and that
      facilitates our understanding of the relationship between phenotypic effects and
      evolutionary processes. In this study, we investigate missense mutations in the
      GCK gene by using a wide array of evolution- and structure-based computational
      methods, such as SIFT, PolyPhen2, PhD-SNP, SNAP, SNPs&GO, fathmm, and Align GVGD.
      Based on the computational prediction scores obtained using these methods, three
      mutations, namely E70K, A188T, and W257R, were identified as highly deleterious
      on the basis of their effects on protein structure and function. Using the
      evolutionary conservation predictors Consurf and Scorecons, we further
      demonstrated that most of the predicted deleterious mutations, including E70K,
      A188T, and W257R, occur in highly conserved regions of GCK. The effects of the
      mutations on protein stability were computed using PoPMusic 2.1, I-mutant 3.0,
      and Dmutant. We also conducted molecular dynamics (MD) simulation analysis
      through in silico modelling to investigate the conformational differences between
      the native and the mutant proteins and found that the identified deleterious
      mutations alter the stability, flexibility, and solvent-accessible surface area
      of the protein. Furthermore, the functional role of each SNP in GCK was
      identified and characterised using SNPeffect 4.0, F-SNP, and FASTSNP. We hope
      that the observed results aid in the identification of disease-associated
      mutations that affect protein structure and function. Our in silico findings
      provide a new perspective on the role of GCK mutations in MODY2 from an evolution
      based structure-centric point of view. The computational architecture described
      in this paper can be used to predict the most appropriate disease phenotypes for
      large-genome sequencing projects and to provide individualised drug therapy for
      complex diseases such as diabetes. 

PMID- 24578723
TI  - Highly efficient hierarchical micelles integrating photothermal therapy and
      singlet oxygen-synergized chemotherapy for cancer eradication.
AB  - It is highly desirable to develop theranostic nanoparticles for achieving cancer
      imaging with enhanced contrast and simultaneously multimodal synergistic therapy.
      Herein, we report a theranostic micelle system hierarchically assembling cyanine
      dye (indocyanine green) and chemotherapeutic compound (doxorubicin) (I/D
      Micelles) as a novel theranostic platform with high drug loading, good stability
      and enhanced cellular uptake via clathrin-mediated endocytosis. I/D-Micelles
      exhibit the multiple functionalities including near-infrared fluorescence (NIRF),
      hyperthermia and intracellular singlet oxygen from indocyanine green, and
      simultaneous cytotoxicity from doxorubicin. Upon photoirradiation, I/D-Micelles
      can induce NIRF imaging, acute photothermal therapy via hyperthermia and
      simultaneous synergistic chemotherapy via singlet oxygen-triggered disruption of
      lysosomal membranes, eventually leading to enhanced NIRF imaging and superior
      tumor eradication without any re-growth. Our results suggest that the
      hierarchical micelles can act as a superior theranostic platform for cancer
      imaging and multimodal synergistic therapy. 

PMID- 24578722
TI  - Nanobody: the "magic bullet" for molecular imaging?
AB  - Molecular imaging involves the non-invasive investigation of biological processes
      in vivo at the cellular and molecular level, which can play diverse roles in
      better understanding and treatment of various diseases. Recently, single domain
      antigen-binding fragments known as 'nanobodies' were bioengineered and tested for
      molecular imaging applications. Small molecular size (~15 kDa) and suitable
      configuration of the complementarity determining regions (CDRs) of nanobodies
      offer many desirable features suitable for imaging applications, such as rapid
      targeting and fast blood clearance, high solubility, high stability, easy
      cloning, modular nature, and the capability of binding to cavities and difficult
      to-access antigens. Using nanobody-based probes, several imaging techniques such
      as radionuclide-based, optical and ultrasound have been employed for
      visualization of target expression in various disease models. This review
      summarizes the recent developments in the use of nanobody-based probes for
      molecular imaging applications. The preclinical data reported to date are quite
      promising, and it is expected that nanobody-based molecular imaging agents will
      play an important role in the diagnosis and management of various diseases. 

PMID- 24578724
TI  - Positron emission tomography (PET) imaging of prostate cancer with a gastrin
      releasing peptide receptor antagonist--from mice to men.
AB  - Ex vivo studies have shown that the gastrin releasing peptide receptor (GRPr) is
      overexpressed on almost all primary prostate cancers, making it a promising
      target for prostate cancer imaging and targeted radiotherapy. METHODS:
      Biodistribution, dosimetry and tumor uptake of the GRPr antagonist 64Cu-CB-TE2A
      AR06 [(64Cu-4,11-bis(carboxymethyl)-1,4,8,11-tetraazabicyclo(6.6.2)hexadecane)
      PEG4-D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-LeuNH2] were studied by PET/CT in four
      patients with newly diagnosed prostate cancer (T1c-T2b, Gleason 6-7). RESULTS: No
      adverse events were observed after injection of 64Cu-CB-TE2A-AR06. Three of four
      tumors were visualized with high contrast [tumor-to-prostate ratio > 4 at 4 hours
      (h) post injection (p.i.)], one small tumor (T1c, < 5% tumor on biopsy specimens)
      showed moderate contrast (tumor-to-prostate ratio at 4 h: 1.9). Radioactivity was
      cleared by the kidneys and only the pancreas demonstrated significant
      accumulation of radioactivity, which rapidly decreased over time. CONCLUSION:
      64Cu-CB-TE2A-AR06 shows very favorable characteristics for imaging prostate
      cancer. Future studies evaluating 64Cu-CB-TE2A-AR06 PET/CT for prostate cancer
      detection, staging, active surveillance, and radiation treatment planning are
      necessary.

PMID- 24578725
TI  - Cell labeling and tracking method without distorted signals by phagocytosis of
      macrophages.
AB  - Cell labeling and tracking are important processes in understanding biologic
      mechanisms and the therapeutic effect of inoculated cells in vivo. Numerous
      attempts have been made to label and track inoculated cells in vivo; however,
      these methods have limitations as a result of their biological effects, including
      secondary phagocytosis of macrophages and genetic modification. Here, we
      investigated a new cell labeling and tracking strategy based on metabolic
      glycoengineering and bioorthogonal click chemistry. We first treated cells with
      tetra-acetylated N-azidoacetyl-D-mannosamine to generate unnatural sialic acids
      with azide groups on the surface of the target cells. The azide-labeled cells
      were then transplanted to mouse liver, and dibenzyl cyclooctyne-conjugated Cy5
      (DBCO-Cy5) was intravenously injected into mice to chemically bind with the azide
      groups on the surface of the target cells in vivo for target cell visualization.
      Unnatural sialic acids with azide groups could be artificially induced on the
      surface of target cells by glycoengineering. We then tracked the azide groups on
      the surface of the cells by DBCO-Cy5 in vivo using bioorthogonal click chemistry.
      Importantly, labeling efficacy was enhanced and false signals by phagocytosis of
      macrophages were reduced. This strategy will be highly useful for cell labeling
      and tracking. 

PMID- 24578728
TI  - "The times they are a changin'!!!".

PMID- 24578729
TI  - Showing your cards.

PMID- 24578730
TI  - Making it hard to rationalize gift exchanges.

PMID- 24578731
TI  - Building a foundation of honesty, integrity and transparency.

PMID- 24578726
TI  - Combining microbubbles and ultrasound for drug delivery to brain tumors: current
      progress and overview.
AB  - Malignant glioma is one of the most challenging central nervous system (CNS)
      diseases, which is typically associated with high rates of recurrence and
      mortality. Current surgical debulking combined with radiation or chemotherapy has
      failed to control tumor progression or improve glioma patient survival.
      Microbubbles (MBs) originally serve as contrast agents in diagnostic ultrasound
      but have recently attracted considerable attention for therapeutic application in
      enhancing blood-tissue permeability for drug delivery. MB-facilitated focused
      ultrasound (FUS) has already been confirmed to enhance CNS-blood permeability by
      temporally opening the blood-brain barrier (BBB), thus has potential to enhance
      delivery of various kinds of therapeutic agents into brain tumors. Here we review
      the current preclinical studies which demonstrate the reports by using FUS with
      MB-facilitated drug delivery technology in brain tumor treatment. In addition, we
      review newly developed multifunctional theranostic MBs for FUS-induced BBB
      opening for brain tumor therapy. 

PMID- 24578732
TI  - The Sunshine Act: Not a good guy versus bad guy issue.

PMID- 24578727
TI  - Photosensitive fluorescent dye contributes to phototoxicity and inflammatory
      responses of dye-doped silica NPs in cells and mice.
AB  - Dye-doped fluorescent silica nanoparticles provide highly intense and photostable
      fluorescence signals. However, some dopant dye molecules are photosensitive. A
      widely-used photosensitive fluorescent dopant, RuBpy, was chosen to
      systematically investigate the phototoxicity of the dye-doped silica
      nanoparticles (NPs). We investigated cell viability, DNA damage, and Reactive
      Oxygen Species (ROS) levels in alveolar macrophages using the dye-doped NPs with
      or without irradiation. Our results showed that the RuBpy-doped silica NPs could
      induce significant amount of ROS, DNA damage, apoptosis and impaired
      proliferation in MH-S cells. In vivo studies in mice showed that RuBpy-doped
      silica NPs induced significant inflammatory cytokine production and lowered
      expression in signaling proteins such as ERK1/2 and NF-kappaB as well as
      increased lung injury determined by myeloperoxidase and lipid peroxidation.
      Strikingly, we also found that both RuBpy alone and NPs induced systemic
      signaling activation in the kidney compared to the liver and lung where showed
      highly selective signaling patterns, which is more pronounced than RuBpy-doped
      silica NPs. Moreover, we discovered a critical biomarker (e.g., HMGB1) for silica
      NPs-induced stress and toxicity and demonstrated differentially-regulated
      response patterns in various organs. Our results indicate for the first time that
      the RuBpy-doped silica NPs may impose less inflammatory responses but stronger
      thermotherapeutic effects on target cells in animals than naked NPs in a time-
      and dose-dependent manner. 

PMID- 24578733
TI  - Relationships with industry: A fine balance.

PMID- 24578734
TI  - Changing times indeed.

PMID- 24578735
TI  - Mentorship is everyone's responsibility.

PMID- 24578736
TI  - Is North America the best place for PCNL in obese patients?

PMID- 24578737
TI  - Continuing medical education: The perspective of quality improvement.

PMID- 24578720
TI  - PI3K-AKT-mTOR-signaling and beyond: the complex network in gastroenteropancreatic
      neuroendocrine neoplasms.
AB  - Gastroenteropancreatic neuroendocrine neoplasms are heterogeneous in their
      clinical behavior and require therapies specially tailored according to staging,
      grading, origin and expression of peptide receptors. Despite extensive scientific
      efforts, the therapy options are still not satisfactory. The main reasons are due
      to the lack of a broad mechanistic knowledge, an insufficient classification of
      specific diagnostic sub-groups, and predictive markers. GEP-NEN tumors evade
      early diagnosis because of slow asymptomatic growth behavior and are frequently
      not detected until metastasized. How signaling networks contribute to tumor
      progression and how these networks interact remains unclear in large parts. In
      this review we summarize the knowledge on the growth factor responsive non
      angiogenetic pathways in sporadic GEP-NENs, highlight promising mechanistic
      research approaches, and describe important therapy targets. 

PMID- 24578739
TI  - Handling patients with growing small renal masses.

PMID- 24578738
TI  - Growth kinetics of small renal masses: A prospective analysis from the Renal Cell
      Carcinoma Consortium of Canada.
AB  - INTRODUCTION: Most small renal masses (SRMs) are diagnosed incidentally and have
      a low malignant potential. As more elderly patients and infirm patients are
      diagnosed with SRMs, there is an increased interest in active surveillance (AS)
      with delayed intervention. Patient and tumour characteristics relating to
      aggressive disease have not been well-studied. The objective was to determine
      predictors of growth of SRMs treated with AS. METHODS: A multicentre prospective
      phase 2 clinical trial was conducted on 207 SRMs in 169 patients in 8
      institutions in Canada from 2004 to 2009; in these patients treatment was delayed
      until disease progression. Patient and tumour characteristics were evaluated to
      determine predictors of growth of SRMs by measuring rates of change in growth (on
      imaging) over time. All patients underwent AS for presumed renal cell carcinoma
      (RCC) based on diagnostic imaging. We used the following factors to develop a
      predictive model of tumour growth with binary recursive partitioning analysis:
      patient characteristics (age, symptoms at diagnosis) and tumour characteristics
      (consistency [solid vs. cystic] and maximum diameter at diagnosis. RESULTS: With
      a median follow-up of 603 days, 169 patients (with 207 SRMs) were followed
      prospectively. Age, symptoms at diagnosis, tumour consistency and maximum
      diameter of the renal mass were not predictors of growth. This cohort was limited
      by lack of availability of patient and tumour characteristics, such as sex,
      degree of endophytic component and tumour location. CONCLUSION: Slow growth rates
      and the low malignant potential of SRMs have led to AS as a treatment option in
      the elderly and infirm population. In a large prospective cohort, we have shown
      that age, symptoms, tumour consistency and maximum diameter of the mass at
      diagnosis are not predictors of growth of T1a lesions. More knowledge on
      predictors of growth of SRMs is needed.

PMID- 24578740
TI  - Testosterone deficiency syndrome and cardiovascular health: An assessment of
      beliefs, knowledge and practice patterns of general practitioners and
      cardiologists in Victoria, BC.
AB  - INTRODUCTION: Testosterone deficiency syndrome (TDS) has been shown to be an
      independent cardiovascular risk factor and a predisposing factor for metabolic
      syndrome. As general practitioners and cardiologists primarily care for these
      patients, we sought to assess their knowledge, beliefs and practice patterns with
      respect to TDS and cardiac health. METHODS: We distributed a questionnaire to all
      20 cardiologists and a cohort of 128 family practitioners in Victoria, British
      Columbia. Of the 13 questions, 10 assessed knowledge and beliefs on TDS and 3
      assessed current practice patterns. RESULTS: Most respondents believed that TDS
      is a medical condition (66.7%) and could negatively affect body composition
      (62%), but a similar majority was unsure whether it was a cardiac risk factor
      (66.7%). While most believed that testosterone replacement therapy (TRT) could
      improve exercise tolerance (62%), most were unsure if it was beneficial in
      cardiac patients. Cardiologists were significantly less likely to believe that
      TRT was beneficial in preventing recurrent myocardial infarction and improving
      myocardial perfusion (p = 0.0133, 0.00186, respectively). The vast majority (88%)
      did not screen cardiac patients for TDS. If a patient was identified as having
      TDS, only10% of those surveyed would refer these patients to a urologist.
      CONCLUSION: Despite its prevalence in cardiac patients, TDS is not well
      understood by general practitioners and cardiologists; they lack knowledge on its
      deleterious cardiovascular effects. In their role as men's health advocates,
      urologists should educate our colleagues regarding the correlation between TDS
      and cardiovascular mortality and risk factors. Limitations of this study include
      small sample size and restricted geographic scope.

PMID- 24578741
TI  - Testosterone deficiency syndrome and cardiovascular health: Looking carefully at
      the evidence.

PMID- 24578742
TI  - Organ procurement surgery as a means of increasing open surgical experience
      during urology residency training.
AB  - INTRODUCTION: The introduction and advancement of minimally invasive surgery
      (MIS) has resulted in a reciprocal decline in exposure to open surgery during
      urology residency training. We propose organ procurement surgery as a potential
      vehicle to facilitate an increase in open surgical experience among trainees. We
      define the surgical case volume for organ procurement surgeries currently
      performed by urology residents in Canada, and determine what capacity exists for
      expansion. METHODS: Data on organ procurement surgeries were extracted for
      Canadian urology residents case-logs between 2005 and 2009. Case-logs were
      anonymously analyzed through the voluntary self-reporting program T-Res
      (Resilience Software Inc.). National deceased organ donor data were obtained from
      the Canadian Institute for Health Information. RESULTS: The graduating Canadian
      urology resident has performed an average of 0.95 organ procurement surgeries
      during 5 years of training. An average of 469.6 procurement surgeries were
      performed yearly in Canada between 2005 and 2009. The theoretical capacity exists
      for each graduating resident to perform an additional 16.3 organ procurements
      during residency. CONCLUSIONS: With the establishment of MIS as standard of care
      for many urologic surgeries, the decrease in open operative experience is
      concerning. Innovative ways to enrich open surgical experience may be required,
      and increased formal incorporation of organ procurements into urology residency
      training curriculum may help fill the void.

PMID- 24578743
TI  - Maintaining open surgical skills in current day urology residency.

PMID- 24578744
TI  - Ochratoxin A is not detectable in renal and testicular tumours.
AB  - INTRODUCTION: Ochratoxin-A (OTA) is one of the most abundant food-contaminating
      mycotoxins, known for its nephrotoxicity, neurotoxicity, gonadotoxicity,
      teratogenicity, immunosuppression and carcinogenesis. OTA has been linked to
      several genitourinary pathologies, including Balkan nephropathy and genitourinary
      malignancies. We examine OTA levels in serum samples and tumour specimens
      collected from patients with renal and testicular tumours. METHODS: Frozen
      samples were obtained from the Ontario Tumour Bank. Serum specimens, along with
      renal and testicular tumour biopsies, were included in this study. Normal tissue
      from the negative surgical margins of each tumour served as a control. OTA levels
      in serum was measured using the enzyme-linked immunosorbent assay (ELISA), while
      OTA detection in tissue specimens was determined using immunohistochemistry
      (IHC). RESULTS: We included specimens collected from 56 patients (36 men and 20
      women). Histopathology of the 52 renal tumours included 31 (60%) conventional
      type renal cell carcinomas (RCC), 5 (10%) chromophobe RCC, 5 (10%) papillary RCC,
      1 (2%) oncocytoma and 10 (19%) upper tract urothelial carcinoma (UC). The 4
      testicular tumours included 1 seminomatous (25%) germ cell tumour and 3 (75%) non
      seminomatous germ cell tumours. OTA was detected in the serum of renal tumour
      patients, with a range from 0.004 to 0.25 ng/mL (mean: 0.07 and median 0.06
      ng/mL). There was no OTA signal detected by IHC staining in all tested renal and
      testicular tumours. CONCLUSIONS: The OTA levels detected in the serum of patients
      were highly variable and relatively low. No OTA was detected in the tissue
      samples.

PMID- 24578745
TI  - Concordance between transrectal ultrasound guided biopsy results and radical
      prostatectomy final pathology: Are we getting better at predicting final
      pathology?
AB  - INTRODUCTION: Inaccuracy in biopsy Gleason scoring poses a risk to men who may
      then receive inappropriate treatment. We assess whether there was a change in
      discordance rates between biopsy and radical prostatectomy at our institution in
      recent years, while considering the implementation of active surveillance and the
      shift in biopsy scores caused by the 2005 International Society of Urologic
      Pathology update to the Gleason scoring protocol. METHODS: We reviewed patients
      who underwent radical prostatectomy at our institution between May 2004 and April
      2011. We analyzed clinical and pathological correlates of upgrading in 3
      subgroups: Gleason sum (GS) 6/6, GS6/7 and GS7/7, where the sum preceding the
      dash was determined from biopsy and the subsequent sum was determined from the
      radical prostatectomy specimen. We applied the log-rank test and Cox model to a
      Kaplan Meier analysis of biochemical recurrence in the subgroups, and also mapped
      GS6/7 discordance over time. RESULTS: In total, 1717 patients met our inclusion
      criteria. The 3 subgroups had significantly different mean prostate-specific
      antigen, patient age, tumour volume, margin status, pathologic stage, prostate
      weight, transrectal ultrasound volume and rate of progression (p < 0.05). We
      noted a multiphasic trend with a fall in discordance after 2005. However, there
      was no sustained trend over the study period taken as a whole (p = 0.06).
      CONCLUSIONS: Although no sustained trend was observed, the falling discordance
      after 2005 may reflect the accommodation to the Gleason scoring update, while the
      gradual adoption of active surveillance may have led to the otherwise increasing
      trends. However, our observations may also be spurious biopsy sampling errors.

PMID- 24578746
TI  - Urological resident exposure to transurethral surgical options for BPH management
      in 2012-2013: A pan-Canadian survey.

PMID- 24578747
TI  - Oncological outcomes of partial nephrectomy for tumours larger than 4 cm: A
      systematic review.
AB  - INTRODUCTION: Many medical associations recommend nephron-sparing surgery (NSS)
      for tumours larger than 4 cm amenable to partial nephrectomy (PN). These
      recommendations are, however, mostly based on isolated reports. We systematically
      review the oncological outcomes of partial nephrectomy procedures performed for
      tumours larger than 4-cm. METHODS: A PubMed search was carried out using keywords
      "partial nephrectomy" and "nephron sparing" for records dating back to 1995. In
      total, 2136 abstracts were analyzed; from these, 174 studies were scrutinized. We
      identified 32 manuscripts reporting size-specific cancer-specific survival rates
      for masses greater than 4 cm. From each of these studies, we recorded the number
      of PN, tumour diameter, follow-up duration, 5- and 10-year recurrence, overall
      and cancer-specific survival rates (OS, CSS). We also calculated weighted OS and
      CSS rates. RESULTS: This systematic review includes 2445 patients with renal
      tumours larger than 4 cm who underwent PN: 1858 patients with tumours between 4
      to 7 cm, 410 patients with tumours larger than 7 cm and 177 patients with tumours
      greater than 4 cm (exact size unknown). Our analysis revealed weighted 5-year CSS
      rates of 95.4%, 86.2% and 93.9% for tumours 4 to 7 cm, >7 cm, and all tumours >4
      cm, respectively. The respective 5-year OS rates were 84.7%, 76.4%, and 84.7%.
      CONCLUSIONS: We found excellent 5-year CSS and OS rates for patients with tumours
      4 to 7 cm treated with PN. These outcomes compare favourably to those reported in
      historical radical nephrectomy (RN) series for similarly sized tumours. Thus, PN
      is an acceptable and often preferred treatment for renal masses >4 cm which are
      amenable to nephron-sparing procedures.

PMID- 24578749
TI  - Coronary artery disease in women: an unsolved dilemma.
AB  - Cardiovascular disease (CVD) is the leading cause of death in women, as well as
      an important cause of disability, although many women and their physicians
      underestimate the risk. The pathogenesis, presentation and diagnosis of CVDs are
      different in women than men, which make the women prone to under-treatment for
      these diseases. More gender-based research regarding the management of coronary
      artery disease (CAD) in women needs to be done. Exercise, hypertension treatment,
      smoking cessation and aspirin therapy are effective measures for the primary
      prevention of CAD in women. The roles of hormone replacement therapy in primary
      prevention are not well established. Hormone replacement therapy has not been
      effective in lowering the risk of recurrent myocardial infarction. Cardiologists
      and family physicians should emphasize the use of proven treatments, with
      particular attention given to underserved populations. 

PMID- 24578750
TI  - Lack of Clinical Benefit of Thromboprophylaxis in Patients Hospitalized in a
      Medical Unit Over a 10-year Span.
AB  - BACKGROUND: Thromboprophylaxis for hospitalized patients with a high risk of
      venous thromboembolic events (VTEs) is strongly recommended but is not
      universally applied on medical units. Outside of randomized trials, there is
      minimal evidence that the usual medications reduce the incidence of clinically
      significant VTE. METHODS: We conducted a retrospective cohort study including all
      patients admitted into a teaching medical unit during years 2001-2002, 2003-2004,
      2005-2006, 2007-2008 and 2009-2010. Inclusion criteria for the analysis were
      having one or more risk factors for a VTE and no contraindication to
      thromboprophylaxis. RESULTS: Of 2,369 patients reviewed, 1,302 satisfied the
      inclusion criteria. Between years 2001-2002 and 2009-2010, the proportion of
      patients receiving thromboprophylaxis increased from 29.2% to 76.4% (P < 0.0001)
      and the duration of thromboprophylaxis increased from 63% of hospital stay to 84%
      (P = 0.004). There was no statistically significant association between the
      number of risk factors and the rate of thromboprophylaxis. Overall, only 32
      patients suffered from a VTE with no decrease in VTE incidence between years 2001
      2002 and 2009-2010. A total of 107 patients had a bleeding event, and there was
      no statistically significant change in the incidence of bleeding during our study
      period. CONCLUSIONS: In our medical units, we found a statistically significant
      increase in the use of the thromboprophylaxis practice. However, this was not
      associated with any statistically significant impact on the VTE incidence. This
      suggests that patients given thromboprophylaxis could be better selected.

PMID- 24578748
TI  - Levosimendan in critical illness: a literature review.
AB  - Levosimendan, the active enantiomer of simendan, is a calcium sensitizer
      developed for treatment of decompensated heart failure, exerts its effects
      independently of the beta adrenergic receptor and seems beneficial in cases of
      severe, intractable heart failure. Levosimendan is usually administered as 24-h
      infusion, with or without a loading dose, but dosing needs adjustment in patients
      with severe liver or renal dysfunction. Despite several promising reports, the
      role of levosimendan in critical illness has not been thoroughly evaluated.
      Available evidence suggests that levosimendan is a safe treatment option in
      critically ill patients and may reduce mortality from cardiac failure. However,
      data from well-designed randomized controlled trials in critically ill patients
      are needed to validate or refute these preliminary conclusions. This literature
      review is an attempt to synthesize available evidence on the role and possible
      benefits of levosimendan in critically ill patients with severe heart failure. 

PMID- 24578751
TI  - Ten years experience with belatacept-based immunosuppression after kidney
      transplantation.
AB  - BACKGROUND: Belatacept was approved for prevention of acute rejection in adult
      kidney transplantation in 2011 based on two randomized, controlled, multicenter
      phase 3 studies. Long-term experience over 10 years with belatacept-based
      immunosuppression after kidney transplantation has not been reported before.
      PATIENTS AND METHODS: Analyzed were 20 patients who had been included into a
      randomized multicenter phase 2 study by our institution between March 2001 and
      November 2002. For 10-year follow-up, three different groups could be analyzed:
      1) patients with primary calcineurin inhibitor-based (CNI-based)
      immunosuppression (n = 5), 2) patients with early switch from a belatacept-based
      to a CNI-based regimen within the first 14 months (n = 8) and 3) patients with
      completely CNI-free belatacept immunosuppression (n = 7). RESULTS: Fifteen
      patients received primary belatacept-based immunosuppression and five patients
      primary cyclosporine A (CyA). Five patients are still on belatacept. Kidney
      function measured by serum creatinine levels worsened in the CNI group and the
      belatacept to CNI switch group during long-term follow-up whereas all patients
      receiving belatacept throughout follow-up showed stable creatinine values. Acute
      rejections occurred predominantly in the first 12 months after transplantation
      and were responsible for four of seven switches from belatacept- to CNI-based
      immunosuppression within the first 14 months. Five of the 20 patients died.
      CONCLUSIONS: Belatacept is effective and safe in renal transplant patients and
      was not associated with graft loss due to chronic allograft nephropathy.
      Belatacept was well tolerated in all patients and caused less nephrotoxic side
      effects and was well accepted in most patients.

PMID- 24578752
TI  - Impact of neuropathic pain at the population level.
AB  - BACKGROUND: One of the chief complaints of individuals who frequent the Family
      Health Units is chronic pain which, in Salvador, affects over 40% of the
      population. However, little is known about the type of pain and its impact on
      quality of life (QoL) at population level. The aim of the study is to evaluate
      the impact of neuropathic pain on QoL in a community. METHODS: A descriptive
      cross-sectional study was conducted from March to October 2012, in a Family
      Health Unit, Salvador, Bahia, Brazil. The DN-4 (type of pain), body map
      (location), VAS (intensity) and SF-36 (QoL) instruments were applied. The Chi
      square (univariate analysis) and logistic regression (multivariate) tests were
      used, with IC 95% and P < 0.05. RESULTS: In a sample of 191 individuals with
      chronic pain, predominantly women (86.4%), single (48.7%), nonwhite (93.2%), low
      educational (46.6%) and low economic (100%) level. The most affected locations of
      the body were knees, lumbar region and head. In 60.2% of interviewees,
      neuropathic pain, of high intensity (VAS = 7.09 +/- 3.0) predominated, with
      duration of 8.53 +/- 8.8 years and mean QoL was reduced in 47.13%. CONCLUSIONS:
      Intense pain in the dorsal region and type of neuropathy are independent
      predictors for greater compromise of QoL.

PMID- 24578753
TI  - Resident knowledge of colorectal cancer screening assessed by web-based survey.
AB  - BACKGROUND: To evaluate resident knowledge of colorectal cancer (CRC) screening
      guidelines and to define areas requiring attention. METHODS: A survey was created
      using three published guidelines for CRC screening. Program directors for
      internal medicine residency programs were contacted within the metro New York
      City area to have their residents participate. RESULTS: Five programs
      participated, and 115 responses were recorded. For the appropriate testing and
      interval to screen for CRC, 61/115 residents identified flexible sigmoidoscopy
      every 5 years, 108/115 identified colonoscopy every 10 years, 16/115 identified
      double contrast barium enema (DCBE) every 5 years and only 12/115 thought CT
      colography every 5 years was appropriate. Only 40/115 respondents appropriately
      identified fecal occult blood testing (FOBT) administered in the patient's home
      annually, while fecal immunohistochemical testing (FIT) annually at home was
      identified by 8/115 residents. CONCLUSION: While most residents seem
      knowledgeable regarding CRC screening with colonoscopy, many deficiencies remain.
      FOBT for screening purposes remains undervalued, and confusion about
      administering the test persists. The distinction between screening and prevention
      needs further reinforcement.

PMID- 24578754
TI  - Efficacy of combination therapy with sitagliptin and low-dose glimepiride in
      Japanese patients with type 2 diabetes.
AB  - BACKGROUND: We examined the effects of combination therapy with 50 mg/day of
      sitagliptin and low-dose glimepiride (1 mg/day) in patients with type 2 diabetes.
      METHODS: Twenty-six patients with poorly controlled type 2 diabetes currently
      taking high-dose glimepiride (>= 2 mg/day) were enrolled in the study. The dose
      of glimepiride was reduced to 1 mg/day and 50 mg/day of sitagliptin was added
      without changing the doses of any other antihyperglycemic agents. The patients
      were divided into two groups: the low-dose group (2 or 3 mg glimepiride decreased
      to 1 mg: n = 15) and the high-dose group (4 or 6 mg glimepiride decreased to 1
      mg: n = 11). RESULTS: Combination therapy significantly lowered HbA1c after 24
      weeks of treatment in both groups. In the low-dose group, 8.1 +/- 0.2% decreased
      to 7.0 +/- 0.1%; in the high-dose group, 8.4 +/- 0.1% decreased to 7.3 +/- 0.2%.
      The time course of the degree of HbA1c reduction in the high-dose group was
      almost superimposable on that in the low-dose group. There were no changes in
      body weight and no hypoglycemia and in either group during the study period. In
      conclusion, our results suggested that the combination therapy used in the study
      is both well tolerated and effective. CONCLUSION: This study indicated the
      usefulness of dipeptidyl peptidase (DPP)-4 inhibitors in Japanese patients with
      type 2 diabetes, and also reinforces the importance of low doses of sulfonylurea
      for effective glycemic management.

PMID- 24578755
TI  - Assessment of Interleukins IL-4, IL-6, IL-8, IL-10 in Acute Urticaria.
AB  - BACKGROUND: Urticaria is a skin disease that affects approximately 5% of the
      general population and manifests itself, not only as an acute but also as a
      chronic disease. The etiology of the disease varies as well as its clinical
      manifestations which extend from the presence of urticarial hives to the
      potentially mortal angioedema. There is a great interest to the disease not only
      due to its special clinical manifestation but also due to its pathogenetic
      mechanism. New data in the medical bibliography support the participation of
      interleukins (ILs) in the pathophysiology of urticaria. The aim of the study is
      to contribute in the comprehension of possible participation of certain ILs in
      the pathogenesis of acute urticaria. METHODS: Our study concerns four ILs, IL-4,
      IL-6, IL-8 and IL-10, simultaneously and their quantitative changes during the
      acute phase of urticaria as well as 2 weeks after drug administration. Moreover,
      ILs levels of patients were compared with those of matched healthy controls. All
      measurements have been done by the ELISA method. The statistical analysis was
      done by SPSS. RESULTS: The results present increased levels (in 51 patients vs.
      22 matched healthy controls) of all four ILs during the acute phase. Especially
      for IL-4 this increase was statistically very significant (P < 0.001).
      Statistically marginally significant decrease was also observed for IL-10
      concentrations (P < 0.059), for the two blood samples (acute phase and 2 weeks
      later). CONCLUSION: It is suggested by the present study that certain ILs might
      play an important role in the pathogenetic mechanism of urticaria. IL-4 and IL-10
      participation seems to be relatively more significant. Possibly, ILs, liberated
      by mast cells, induce an influx of leukocytes in the dermis, therefore
      participating in the development of acute urticaria inflammation.

PMID- 24578757
TI  - Extracorporeal membrane oxygenation in diffuse alveolar hemorrhage secondary to
      systemic lupus erythematosus.
AB  - Diffuse alveolar hemorrhage (DAH) is a rare and potentially deadly complication
      of systemic lupus erythematosus (SLE). We report two adult cases where
      extracorporeal membrane oxygenation (ECMO) was used as rescue therapy for severe
      respiratory failure in this setting. We discuss the risk related to coagulation
      disturbance and the need for the circuit anticoagulation in this particular
      setting. We also briefly discuss the clinical problem of lack of knowledge on the
      bioavailability of the immunosuppressive treatment with the use of ECMO. We think
      that ECMO should be used as rescue therapy in patients with DAH caused by SLE,
      but strategies for anticoagulation require further precision. 

PMID- 24578756
TI  - Is a switch from insulin therapy to liraglutide possible in Japanese type 2
      diabetes mellitus patients?
AB  - BACKGROUND: To evaluate the efficacy of switching from insulin to the GLP-1
      receptor agonist liraglutide in type 2 diabetes mellitus patients. METHODS: The
      subjects were 231 outpatients with type 2 diabetes mellitus being treated with
      liraglutide for the first time. For 161 patients, liraglutide was continued for
      24 weeks (continuation group), and for 70 patients, liraglutide was discontinued
      before 24 weeks (discontinuation group). Fasting and postprandial blood glucose
      levels, HbA1c, body weight, and insulin dose were evaluated before the switch to
      liraglutide (baseline) and at 12 and 24 weeks of administration. Trends in HbA1c
      and weight were compared at 12 and 24 weeks of administration. Multiple
      regression analyses were conducted to identify clinical factors predicting a
      successful switch to liraglutide. RESULTS: Multiple regression analysis with
      DeltaHbA1c as the dependent variable in the continuation group indicated that
      HbA1c at 12 weeks of administration decreased with higher baseline HbA1c and
      increased with higher baseline daily insulin doses. Multiple regression analysis
      with Deltaweight as the dependent variable indicated that Deltaweight at 24 weeks
      of liraglutide administration was higher with higher baseline daily insulin doses
      and longer duration of diabetes. Based on the area under the receiver operating
      characteristic curve, cut-off values of 19 units for daily insulin dose and nine
      years for duration of diabetes were identified. CONCLUSIONS: Switching from
      insulin to liraglutide therapy is possible for carefully selected patients. Daily
      insulin dosage and duration of insulin therapy appear to be clinically useful
      indicators for the efficacy of liraglutide therapy.

PMID- 24578758
TI  - Spontaneous Hemothorax in a Patient With von Recklinghausen's Disease.
AB  - Type I neurofibromatosis (NF-1) is a rare autosomal dominant disease. It can
      affect any organ system including vascular tissues. A 53 years old man, with a
      past medical history of NF-1, retinitis pigmentosa and hypertension attended to
      the emergency department for chest pain and palpitations and was discharged 2
      days after acute coronary syndrome was ruled out. During this admission an
      echocardiogram was performed which showed a left ventricular hypertrophy with
      normal ejection fraction and a chest X-ray which revealed no pathologic images.
      No invasive procedures were preformed. Three days after discharge, he returned to
      our hospital for sudden onset of oppressive chest pain in the right arm,
      irradiated to the ipsilateral shoulder, chest and back. After several tests, a
      diagnosis of hemothorax was made. Hemoglobin levels declined during the first 2
      days of admission from 12.1 to 9.6 g/dL, although the patient remained
      hemodynamic stable. An arteriography was performed, which showed the presence of
      bleeding from a branch of the right subclavian artery, which was selectively
      catheterized and embolized with coils. Afterwards, a video-assisted thoracoscopy
      was made, in order to drain the hemothorax and to carry out a visual review of
      the pleural cavity. The patient had a good clinical and radiologic progression
      and was discharged after few days. After a year of follow-up, the patient has
      remained clinically asymptomatic with no further episodes of active bleeding. 

PMID- 24578759
TI  - Chronic abdominal pain secondary to mesh erosion into ceacum following incisional
      hernia repair: a case report and literature review.
AB  - Incisional hernias following abdominal operations are a common complication. Mesh
      is frequently employed in repair of these hernias. Mesh migration is an
      infrequent occurrence. We present the case of transmural mesh migration from the
      abdominal wall into the ceacum presenting as chronic abdominal pain. Given the
      popularity of minimally invasive surgery utilizing polypropylene mesh for
      incisional hernia repair, related complications such as postoperative hematoma
      and seroma, foreign body reaction, organ injury, infection, mesh rejection and
      fistula are increasingly being noted. Most of the mesh migrations reported in the
      literature involve the urinary bladder. We present a case of delayed mesh
      migration into the ceacum. Mesh migration is a rare and peculiar complication
      that is rarely reported in the literature. A review of the literature shows that
      there are no other cases of mesh migration into ceacum several years after open
      type incisional hernia repair. 

PMID- 24578761
TI  - The Alameda model: an effort worth emulating.

PMID- 24578760
TI  - Effects of a dedicated regional psychiatric emergency service on boarding of
      psychiatric patients in area emergency departments.
AB  - INTRODUCTION: Mental health patients boarding for long hours, even days, in
      United States emergency departments (EDs) awaiting transfer for psychiatric
      services has become a considerable and widespread problem. Past studies have
      shown average boarding times ranging from 6.8 hours to 34 hours. Most proposed
      solutions to this issue have focused solely on increasing available inpatient
      psychiatric hospital beds, rather than considering alternative emergency care
      designs that could provide prompt access to treatment and might reduce the need
      for many hospitalizations. One suggested option has been the "regional dedicated
      emergency psychiatric facility," which serves to evaluate and treat all mental
      health patients for a given area, and can accept direct transfers from other EDs.
      This study sought to assess the effects of a regional dedicated emergency
      psychiatric facility design known at the "Alameda Model" on boarding times and
      hospitalization rates for psychiatric patients in area EDs. METHODS: Over a 30
      day period beginning in January 2013, 5 community hospitals in Alameda County,
      California, tracked all ED patients on involuntary mental health holds to
      determine boarding time, defined as the difference between when they were deemed
      stable for psychiatric disposition and the time they were discharged from the ED
      for transfer to the regional psychiatric emergency service. Patients were also
      followed to determine the percentage admitted to inpatient psychiatric units
      after evaluation and treatment in the psychiatric emergency service. RESULTS: In
      a total sample of 144 patients, the average boarding time was approximately 1
      hour and 48 minutes. Only 24.8% were admitted for inpatient psychiatric
      hospitalization from the psychiatric emergency service. CONCLUSION: The results
      of this study indicate that the Alameda Model of transferring patients from
      general hospital EDs to a regional psychiatric emergency service reduced the
      length of boarding times for patients awaiting psychiatric care by over 80%
      versus comparable state ED averages. Additionally, the psychiatric emergency
      service can provide assessment and treatment that may stabilize over 75% of the
      crisis mental health population at this level of care, thus dramatically
      alleviating the demand for inpatient psychiatric beds. The improved, timely
      access to care, along with the savings from reduced boarding times and
      hospitalization costs, may well justify the costs of a regional psychiatric
      emergency service in appropriate systems.

PMID- 24578762
TI  - Response to Moulin and Jones: "The Alameda Model: an effort worth emulating".

PMID- 24578763
TI  - Increasing suicide rates among middle-age persons and interventions to manage
      patients with psychiatric complaints.
AB  - The Centers for Disease Control and Prevention (CDC) has published significant
      data and trends related to suicide rates in the United States (U.S.). Suicide is
      the 10th leading cause of death in U.S. adults, and rates are increasing across
      all geographic regions. There is a significant increase in the suicide rate among
      adults in the 35-64 age range. We present findings from the CDC's Morbidity and
      Mortality Weekly Report (MMWR) with commentary on current resources and barriers
      to psychiatric care. 

PMID- 24578764
TI  - Patient attitudes regarding consent for emergency department computed
      tomographies.
AB  - INTRODUCTION: Little is known about patient attitudes towards informed consent
      for computed tomography (CT) in the emergency department (ED). We set out to
      determine ED patient attitudes about providing informed consent for CTs. METHODS:
      In this cross-sectional questionnaire-based survey study, we evaluated a
      convenience sample of patients' attitudes about providing informed consent for
      having a CT at 2 institutional sites. Historically, at our institutional network,
      patients received a CT at approximately 25% of their ED visits. The survey
      consisted of 17 "yes/no" or multiple-choice questions. The primary outcome
      question was "which type of informed consent do you feel is appropriate for a CT
      in the Emergency Department?" RESULTS: We analyzed 300 survey responses, which
      represented a 90% return rate of surveys distributed. Seventy-seven percent
      thought they should give their consent prior to receiving a CT, and 95% were
      either comfortable or very comfortable with their physician making the decision
      regarding whether they needed a CT. Forty percent of the patients felt that a
      general consent was appropriate before receiving a CT in the ED, while 34%
      thought a verbal consent was appropriate and 15% percent thought a written
      consent was appropriate. Seventy-two percent of the ED patients didn't expect to
      receive a CT during their ED visit and 30% of the ED patients had previously
      provided consent prior to receiving a CT. CONCLUSION: Most patients feel
      comfortable letting the doctor make the decision regarding the need for a CT.
      Most ED patients feel informed consent should occur before receiving a CT but
      only a minority feel the consent should be written and specific to the test.

PMID- 24578766
TI  - Betrayed mood in public view: Taking a MySpace history.
AB  - Social networking sites (SNS), the modern mainstay of adolescent expression, may
      provide vital information to physicians. The emergency department (ED) is a
      setting where SNS may be helpful. A reticent 19-year-old in the ED prompted a
      search for pertinent information on the Internet, where a profile on
      www.myspace.com relayed a troubled post. The patient was admitted for psychiatric
      evaluation due to intentional overdose. These SNS may provide a venue for
      physicians to learn about risky behaviors and life stressors that would help
      identify underlying medical issues in young adults. We provide a guideline on how
      to utilize SNS with privacy rights in mind. 

PMID- 24578765
TI  - Social media guidelines and best practices: recommendations from the Council of
      Residency Directors Social Media Task Force.
AB  - Social media has become a staple of everyday life among over one billion people
      worldwide. A social networking presence has become a hallmark of vibrant and
      transparent communications. It has quickly become the preferred method of
      communication and information sharing. It offers the ability for various
      entities, especially residency programs, to create an attractive internet
      presence and "brand" the program. Social media, while having significant
      potential for communication and knowledge transfer, carries with it legal,
      ethical, personal, and professional risks. Implementation of a social networking
      presence must be deliberate, transparent, and optimize potential benefits while
      minimizing risks. This is especially true with residency programs. The power of
      social media as a communication, education, and recruiting tool is undeniable.
      Yet the pitfalls of misuse can be disastrous, including violations in patient
      confidentiality, violations of privacy, and recruiting misconduct. These
      guidelines were developed to provide emergency medicine residency programs
      leadership with guidance and best practices in the appropriate use and regulation
      of social media, but are applicable to all residency programs that wish to
      establish a social media presence. 

PMID- 24578767
TI  - Impact of learners on emergency medicine attending physician productivity.
AB  - INTRODUCTION: Several prior studies have examined the impact of learners (medical
      students or residents) on overall emergency department (ED) flow as well as the
      impact of resident training level on the number of patients seen by residents per
      hour. No study to date has specifically examined the impact of learners on
      emergency medicine (EM) attending physician productivity, with regards to
      patients per hour (PPH). We sought to evaluate whether learners increase,
      decrease, or have no effect on the productivity of EM attending physicians in a
      teaching program with one student or resident per attending. METHODS: This was a
      retrospective database review of an urban, academic tertiary care center with 3
      separate teams on the acute care side of the ED. Each team was staffed with one
      attending physician paired with either one resident, one medical student or with
      no learners. All shifts from July 1, 2008 to June 30, 2010 were reviewed using an
      electronic database. We predefined a shift as "Resident" if > 5 patients were
      seen by a resident, "Medical Student" if any patients were seen by a medical
      student, and "No Learners" if no patients were seen by a medical student or
      resident. Shifts were removed from analysis if more than one learner saw patients
      during the shift. We further stratified resident shifts by EM training level or
      off-service rotator. For each type of shift, the total number of patients seen by
      the attending physician was then divided by 8 hours (shift duration) to arrive at
      number of patients per hour. RESULTS: We analyzed a total of 7,360 shifts with
      2,778 removed due to multiple learners on a team. For the 2,199 shifts with
      attending physicians with no learners, the average number of PPH was 1.87(95%
      confidence interval [CI] 1.86,1.89). For the 514 medical student shifts, the
      average PPH was 1.87(95% CI 1.84,1.90), p = 0.99 compared with attending with no
      learner. For the 1,935 resident shifts, the average PPH was 1.99(95% CI
      1.97,2.00). Compared with attending physician with no learner, attending
      physicians with a resident saw more PPH (1.99 vs 1.87, p<0.005). There was no
      statistically significant difference found between EM1: 1.98PPH, EM2: 1.99PPH,
      EM3: 1.99PPH, and off-service rotators: 1.99PPH. CONCLUSION: EM attending
      physicians paired with a resident in a one-on-one teaching model saw
      statistically significantly more patients per hour (0.12 more patients per hour)
      than EM attending physicians alone. EM attending physicians paired with a medical
      student saw the same number of patients per hour compared with working alone.

PMID- 24578768
TI  - Predictors of unattempted central venous catheterization in septic patients
      eligible for early goal-directed therapy.
AB  - INTRODUCTION: Central venous catheterization (CVC) can be an important component
      of the management of patients with severe sepsis and septic shock. CVC, however,
      is a time- and resource-intensive procedure associated with serious
      complications. The effects of the absence of shock or the presence of relative
      contraindications on undertaking central line placement in septic emergency
      department (ED) patients eligible for early goal-directed therapy (EGDT) have not
      been well described. We sought to determine the association of relative
      normotension (sustained systolic blood pressure >90 mmHg independent of or in
      response to an initial crystalloid resuscitation of 20 mL/kg), obesity (body mass
      index [BMI] >=30), moderate thrombocytopenia (platelet count <50,000 per MUL),
      and coagulopathy (international normalized ratio >=2.0) with unattempted CVC in
      EGDT-eligible patients. METHODS: This was a retrospective cohort study of 421
      adults who met EGDT criteria in 5 community EDs over a period of 13 months. We
      compared patients with attempted thoracic (internal jugular or subclavian) CVC
      with those who did not undergo an attempted thoracic line. We also compared
      patients with any attempted CVC (either thoracic or femoral) with those who did
      not undergo any attempted central line. We used multivariate logistic regression
      analysis to calculate adjusted odd ratios (AORs). RESULTS: In our study, 364
      (86.5%) patients underwent attempted thoracic CVC and 57 (13.5%) did not.
      Relative normotension was significantly associated with unattempted thoracic CVC
      (AOR 2.6 95% confidence interval [CI], 1.6-4.3), as were moderate
      thrombocytopenia (AOR 3.9; 95% CI, 1.5-10.1) and coagulopathy (AOR 2.7; 95% CI,
      1.3-5.6). When assessing for attempted catheterization of any central venous site
      (thoracic or femoral), 382 (90.7%) patients underwent attempted catheterization
      and 39 (9.3%) patients did not. Relative normotension (AOR 2.3; 95% CI, 1.2-4.5)
      and moderate thrombocytopenia (AOR 3.9; 95% CI, 1.5-10.3) were significantly
      associated with unattempted CVC, whereas coagulopathy was not (AOR 0.6; 95% CI,
      0.2-1.8). Obesity was not significantly associated with unattempted CVC, either
      thoracic in location or at any site. CONCLUSION: Septic patients eligible for
      EGDT with relative normotension and those with moderate thrombocytopenia were
      less likely to undergo attempted CVC at any site. Those with coagulopathy were
      also less likely to undergo attempted thoracic central line placement. Knowledge
      of the decision-making calculus at play for physicians considering central venous
      catheterization in this population can help inform physician education and
      performance improvement programs.

PMID- 24578769
TI  - Importance of hospital entry: walk-in STEMI and primary percutaneous coronary
      intervention.
AB  - INTRODUCTION: Patients with ST elevation myocardial infarction (STEMI) require
      rapid identification and triage to initiate reperfusion therapy. Walk-in STEMI
      patients have longer treatment times compared to emergency medical service (EMS)
      transported patients. While effective triage of large numbers of critically ill
      patients in the emergency department is often cited as the reason for treatment
      delays, additional factors have not been explored. The purpose of this study was
      to evaluate baseline demographic and clinical differences between walk-in and EMS
      transported STEMI patients and identify factors associated with prolonged door to
      balloon (D2B) time in walk-in STEMI patients. METHODS: We performed a
      retrospective review of 136 STEMI patients presenting to an urban academic
      teaching center from January 2009 through December 2010. Baseline demographics,
      mode of hospital entry (walk-in versus EMS transport), treatment times,
      angiographic findings, procedures performed and in-hospital clinical events were
      collected. We compared walk-in and EMS-transported STEMI patients and identified
      independent factors of prolonged D2B time for walk-in patients using stepwise
      logistic regression analysis. RESULTS: Walk-in patients (n=51) were more likely
      to be Latino and presented with a higher heart rate, higher systolic blood
      pressure, prior history of diabetes mellitus and were more likely to have an
      elevated initial troponin value, compared to EMS-transported patients. EMS
      transported patients (n=64) were more likely to be white and had a higher
      prevalence of left main coronary artery disease, compared to walk-in patients.
      Door to electrocardiogram (ECG), ECG to catheterization laboratory (CL)
      activation and D2B times were significantly longer for walk-in patients. Walk-in
      patients were more likely to have D2B time >90 minutes, compared to EMS-
      transported patients; odds ratio 3.53 (95% CI 1.03, 12.07), p=0.04. Stepwise
      logistic regression identified hospital entry mode as the only independent
      predictor for prolonged D2B time. CONCLUSION: Baseline differences exist between
      walk-in and EMS-transported STEMI patients undergoing primary percutaneous
      coronary intervention (PCI). Hospital entry mode was the most important predictor
      for prolonged treatment times for primary PCI, independent of age, Latino
      ethnicity, heart rate, systolic blood pressure and initial troponin value.
      Prolonged door to ECG and ECG to CL activation times are modifiable factors
      associated with prolonged treatment times in walk-in STEMI patients. In addition
      to promoting the use of EMS transport, efforts are needed to rapidly identify and
      expedite the triage of walk-in STEMI patients.

PMID- 24578770
TI  - The July Effect: is emergency department length of stay greater at the beginning
      of the hospital academic year?
AB  - INTRODUCTION: There has been concern of increased emergency department (ED)
      length of stay (LOS) during the months when new residents are orienting to their
      roles. This so-called "July Effect" has long been thought to increase LOS, and
      potentially contribute to hospital overcrowding and increased waiting time for
      patients. The objective of this study is to determine if the average ED LOS at
      the beginning of the hospital academic year differs for teaching hospitals with
      residents in the ED, when compared to other months of the year, and as compared
      to non-teaching hospitals without residents. METHODS: We performed a
      retrospective analysis of a nationally representative sample of 283,621 ED visits
      from the National Hospital Ambulatory Medical Care Survey (NHAMCS), from 2001 to
      2008. We stratified the sample by proportion of visits seen by a resident, and
      compared July to the rest of the year, July to June, and July and August to the
      remainder of the year. We compared LOS for teaching hospitals to non-teaching
      hospitals. We used bivariate statistics, and multivariable regression modeling to
      adjust for covariates. RESULTS: Our findings show that at teaching hospitals with
      residents, there is no significant difference in mean LOS for the month of July
      (275 minutes) versus the rest of the year (259 min), July and August versus the
      rest of the year, or July versus June. Non-teaching hospital control samples
      yielded similar results with no significant difference in LOS for the same time
      periods. There was a significant difference found in mean LOS at teaching
      hospitals (260 minutes) as compared to non-teaching hospitals (185 minutes)
      throughout the year (p<0.0001). CONCLUSION: Teaching hospitals with residents in
      the ED have slower throughput of patients, no matter what time of year. Thus, the
      "July Effect" does not appear to a factor in ED LOS. This has implications as
      overcrowding and patient boarding become more of a concern in our increasingly
      busy EDs. These results question the need for additional staffing early in the
      academic year. Teaching hospitals may already institute more robust staffing
      during this time, preventing any significant increase in LOS. Multiple factors
      contribute to long stays in the ED. While patients seen by residents stay longer
      in the ED, there is little variability throughout the academic year.

PMID- 24578771
TI  - Electronic medical record utopia may be right before our eyes.

PMID- 24578772
TI  - Sensitivity of emergency bedside ultrasound to detect hydronephrosis in patients
      with computed tomography-proven stones.
AB  - INTRODUCTION: Non-contrast computed tomography (CT) is widely regarded as the
      gold standard for diagnosis of urolithiasis in emergency department (ED)
      patients. However, it is costly, time-consuming and exposes patients to
      significant doses of ionizing radiation. Hydronephrosis on bedside ultrasound is
      a sign of a ureteral stone, and has a reported sensitivity of 72-83% for
      identification of unilateral hydronephrosis when compared to CT. The purpose of
      this study was to evaluate trends in sensitivity related to stone size and
      number. METHODS: This was a structured, explicit, retrospective chart review. Two
      blinded investigators used reviewed charts of all adult patients over a 6-month
      period with a final diagnosis of renal colic. Of these charts, those with CT
      evidence of renal calculus by attending radiologist read were examined for
      results of bedside ultrasound performed by an emergency physician. We included
      only those patient encounters with both CT-proven renal calculi and documented
      bedside ultrasound results. RESULTS: 125 patients met inclusion criteria. The
      overall sensitivity of ultrasound for detection of hydronephrosis was 78.4% [95%
      confidence interval (CI)=70.2-85.3%]. The overall sensitivity of a positive
      ultrasound finding of either hydronephrosis or visualized stones was 82.4%
      [95%CI: 75.6%, 89.2%]. Based on a prior assumption that ultrasound would detect
      hydronephrosis more often in patients with larger stones, we found a
      statistically significant (p=0.016) difference in detecting hydronephrosis in
      patients with a stone >=6 mm (sensitivity=90% [95% CI=82-98%]) compared to a
      stone <6 mm (sensitivity=75% [95% CI=65-86%]). For those with 3 or more stones,
      sensitivity was 100% [95% CI=63-100%]. There were no patients with stones >=6 mm
      that had both a negative ultrasound and lack of hematuria. CONCLUSION: In a
      population with CT-proven urolithiasis, ED bedside ultrasonography had similar
      overall sensitivity to previous reports but showed better sensitivity with
      increasing stone size and number. We identified 100% of patients with stones >=6
      mm that would benefit from medical expulsive therapy by either the presence of
      hematuria or abnormal ultrasound findings.

PMID- 24578773
TI  - Should osteopathic students applying to allopathic emergency medicine programs
      take the USMLE Exam?
AB  - INTRODUCTION: Board scores are an important aspect of an emergency medicine (EM)
      residency application. Residency directors use these standardized tests to
      objectively evaluate an applicant's potential and help decide whether to
      interview a candidate. While allopathic (MD) students take the United States
      Medical Licensing Examination (USMLE), osteopathic (DO) students take the
      Comprehensive Osteopathic Medical Licensing Examination (COMLEX). It is difficult
      to compare these scores. Previous literature proposed an equation to predict
      USMLE based on COMLEX. Recent analyses suggested this may no longer be accurate.
      DO students applying to allopathic programs frequently ask whether they should
      take USMLE to overcome this potential disadvantage. The objective of the study is
      to compare the likelihood to match of DO applicants who reported USMLE to those
      who did not, and to clarify how important program directors consider it is
      whether or not an osteopathic applicant reported a USMLE score. METHODS: We
      conducted a review of Electronic Residency Application Service (ERAS) and
      National Resident Matching Program (NRMP) data for 2010-2011 in conjunction with
      a survey of EM residency programs. We reviewed the number of allopathic and
      osteopathic applicants, the number of osteopathic applicants who reported a USMLE
      score, and the percentage of successful match. We compared the percentage of
      osteopathic applicants who reported a USMLE score who matched compared to those
      who did not report USMLE. We also surveyed allopathic EM residency programs to
      understand how important it is that osteopathic (DO) students take USMLE.
      RESULTS: There were 1,482 MD students ranked EM programs; 1,277 (86%, 95% CI 84.3
      87.9) matched. There were 350 DO students ranked EM programs; 181 (52%, 95% CI
      46.4-57.0) matched (difference=34%, 95% CI 29.8-39.0, p<0.0001). There were 208
      DO students reported USMLE; 126 (61%, 95% CI 53.6-67.2) matched. 142 did not
      report USMLE; 55 (39%, 95% CI 30.7-47.3) matched (difference=22%, 95% CI 11.2
      32.5, p<0.0001). Survey results: 39% of program directors reported that it is
      extremely important that osteopathic students take USMLE, 38% stated it is
      somewhat important, and 22% responded not at all important. CONCLUSION: DO
      students who reported USMLE were more likely to match. DO students applying to
      allopathic EM programs should consider taking USMLE to improve their chances of a
      successful match.

PMID- 24578774
TI  - Asymptomatic chronic dislocation of a cemented total hip prosthesis.

PMID- 24578775
TI  - Usefulness of computed tomography perfusion in treatment of an acute stroke
      patient with unknown time of symptom onset.

PMID- 24578776
TI  - Diagnosis of necrotizing faciitis with bedside ultrasound: the STAFF Exam.
AB  - The early diagnosis of necrotizing fasciitis is often ambiguous. Computed
      tomography and magnetic resonance imaging, while sensitive and specific
      modalities, are often time consuming or unavailable. We present a case of
      necrotizing fasciitis that was rapidly diagnosed using bedside ultrasound
      evaluating for subcutaneous thickening, air, and fascial fluid (STAFF). We
      propose the STAFF ultrasound exam may be beneficial in the rapid evaluation of
      unstable patients with consideration of necrotizing fasciitis, in a similar
      fashion to the current use of a focused assessment with sonography for trauma
      exam in the setting of trauma. 

PMID- 24578777
TI  - Recurrent priapism from therapeutic quetiapine.
AB  - Priapism is rarely related to use of non-erectile related medications. The
      objective was to educate about the multiple possible causes of priapism and to
      provide treatment recommendations for the different types of priapism. We present
      the case of a 43-year-old African American male with a history of schizoaffective
      disorder who presented to our emergency department multiple times over a three
      year period with priapism, each episode related to the ingestion of quetiapine.
      Following penile aspiration and intercavernosal injection of phenylephrine, this
      patient had resolution of his priapism. This case demonstrates an unusual case of
      recurrent priapism. 

PMID- 24578778
TI  - From the Test Tube to the Treatment Room: Fundamentals of Boron-containing
      Compounds and their Relevance to Dermatology.
AB  - The development of new drug classes and novel molecules that are brought to the
      marketplace has been a formidable challenge, especially for dermatologic drugs.
      The relative absence of new classes of antimicrobial agents is also readily
      apparent. Several barriers account for slow drug development, including
      regulatory changes, added study requirements, commercial pressures to bring drugs
      to market quickly by developing new generations of established compounds, and the
      greater potential for failure and higher financial risk when researching new drug
      classes. In addition, the return on investment is usually much lower with
      dermatologic drugs as compared to the potential revenue from "blockbuster" drugs
      for cardiovascular or gastrointestinal disease, hypercholesterolemia, and mood
      disorders. Nevertheless, some researchers are investigating new therapeutic
      platforms, one of which is boron-containing compounds. Boron-containing compounds
      offer a wide variety of potential applications in dermatology due to their unique
      physical and chemical properties, with several in formal phases of development.
      Tavaborole, a benzoxaborole compound, has been submitted to the United States
      Food and Drug Administration for approval for treatment of onychomycosis. This
      article provides a thorough overview of the history of boron-based compounds in
      medicine, their scientific rationale, physiochemical and pharmacologic
      properties, and modes of actions including therapeutic targets. A section
      dedicated to boron-based compounds in development for treatment of various skin
      disorders is also included. 

PMID- 24578779
TI  - Understanding the burden of adult female acne.
AB  - OBJECTIVE: Typically regarded as an adolescent condition, acne among adult
      females is also prevalent. Limited data are available on the clinical
      characteristics and burden of adult female acne. The study objective was to
      describe clinical characteristics and psychosocial impact of acne in adult women.
      DESIGN: Cross-sectional, web-based survey. SETTING: Data were collected from a
      diverse sample of United States females. PARTICIPANTS: Women ages 25 to 45 years
      with facial acne (>=25 visible lesions). MEASUREMENTS: Outcomes included
      sociodemographic and clinical characteristics, perceptions, coping behaviors,
      psychosocial impact of acne (health-related quality of life using acne-specific
      Quality of Life questionnaire and psychological status using Patient Health
      Questionnaire), and work/productivity. RESULTS: A total of 208 women completed
      the survey (mean age 35+/-6 years), comprising White/Caucasian (51.4%),
      Black/African American (24.5%), Hispanic/Latino (11.1%), Asian (7.7%), and Other
      (5.3%). Facial acne presented most prominently on cheeks, chin, and forehead and
      was characterized by erythema, postinflammatory hyperpigmentation, and scarring.
      Average age of adult onset was 25+/-6 years, and one-third (33.7%) were diagnosed
      with acne as an adult. The majority (80.3%) had 25 to 49 visible facial lesions.
      Acne was perceived as troublesome and impacted self-confidence. Makeup was
      frequently used to conceal acne. Facial acne negatively affected health-related
      quality of life, was associated with mild/moderate symptoms of depression and/or
      anxiety, and impacted ability to concentrate on work or school. CONCLUSION:
      RESULTS highlight the multifaceted impact of acne and provide evidence that adult
      female acne is under-recognized and burdensome.

PMID- 24578781
TI  - Congenital self-healing reticulohistiocytosis.
AB  - Congenital self-healing reticulohistiocytosis, also known as congenital self
      healing Langerhans cell histiocytosis or Hashimoto-Pritzker disease, is a
      Langerhans cell histiocytosis. It is characterized by skin lesions in the newborn
      period in an otherwise healthy infant that show a Langerhans cell infiltrate in
      the skin on histological analysis. These findings subsequently spontaneously
      involute. This report describes two newborns who presented at birth with
      differing presentations of congenital self-healing reticulohistiocytosis. A
      review of the disorder, including diagnosis and evaluation, is presented. 

PMID- 24578780
TI  - Incorporation of a barrier protection cream in the management of chronic hand
      dermatitis: focus on data supporting an established hand protectant formulation
      and modifications designed to assist in barrier repair.
AB  - A commonly encountered skin disorder in outpatient dermatology practice is hand
      dermatitis. In a considerable subset of patients, hand dermatitis can be a major
      source of prolonged distress when a pattern of chronicity develops due to
      repeated exposure to a variety of potential etiological factors. Most of the
      etiological factors are exogenous in nature. Hand dermatitis is an equal
      opportunity disease that affects both genders and occurs in individuals from all
      ethnic and cultural backgrounds. It is important to note that the term hand
      dermatitis does not refer to one specific diagnostic entity. Rather, hand
      dermatitis refers to multiple patterns of clinical disease that can be induced by
      a variety of exogenous sources. Occupational exposures with inadequate hand
      protection may be an important cause of epidermal barrier disruption, and in some
      cases contact allergy may be the primary cause or contribute to chronic hand
      dermatitis. In certain individuals, endogenous sources, such as atopic skin,
      cutaneous allergy (eczematous pattern), or skin hypersensitivity (urticarial
      pattern), may innately create predisposition to the development of hand
      dermatitis. Hand dermatitis can become a chronic problem that is often difficult
      to manage effectively. As consistency with hand protection and avoidance of
      irritant and allergenic contactants are integral to the effective treatment of
      chronic hand dermatitis, there is a high dependence on consistent patient
      adherence. Regardless of the etiological factors causing chronic hand dermatitis,
      lack of consistent hand protection is often a major reason why therapeutic
      results are suboptimal in some cases as exposure to the causes of the hand
      dermatitis are not adequately prevented. Regular wearing of protective gloves is
      not always feasible depending on the occupation, and although topically applied
      skin barrier protectants may be helpful in some cases, scientific data are
      generally limited with many products. This article provides an overview of hand
      dermatitis, reviews data supporting the therapeutic benefit of a specific barrier
      protection hand cream, and discusses ingredient modifications to the original
      formulation. The newer formulation does not alter the skin barrier protection
      components; however, the new ingredients were selected to add barrier repair
      properties to the original product, which was designed only as a skin barrier
      protectant. 

PMID- 24578782
TI  - Corticosteroid and fragrance allergy exacerbating scalp psoriasis.
AB  - Increasing evidence indicates that allergic contact dermatitis can worsen pre
      existing psoriasis. The authors highlight a delayed-hypersensitivity reaction to
      a common psoriasis medication and discuss therapeutic interventions. 

PMID- 24578783
TI  - Approaches that ascertain the role of dietary compounds in colonic cancer cells.
AB  - Preventive approaches against cancer have not been fully developed and applied.
      For example, the incidence of some types of cancer, including colon cancer, is
      highly dependent upon lifestyle, and therefore, amenable to prevention. Among the
      lifestyle factors, diet strongly affects the incidence of colon cancer; however,
      there are no definitive dietary recommendations that protect against this
      malignancy. The association between diet-derived bioactives and development of
      colonic neoplasms will remain ill defined if we do not take into account: (1) the
      identity of the metabolites present in the colonic lumen; (2) their
      concentrations in the colon; and (3) the effect of the colonic contents on the
      function of individual bioactives. We review two approaches that address these
      questions: the use of fecal water and in vitro models of the human colon.
      Compared to treatment with individual diet-derived compounds, the exposure of
      colon cancer cells to samples from fecal water or human colon simulators mimics
      closer the in vitro conditions and allows for more reliable studies on the
      effects of diet on colon cancer development. The rationale and the advantages of
      these strategies are discussed from the perspective of a specific question on how
      to analyze the combined effect of two types of bioactives, butyrate and
      polyphenol metabolites, on colon cancer cells. 

PMID- 24578785
TI  - Novel blood-based microRNA biomarker panel for early diagnosis of pancreatic
      cancer.
AB  - AIM: To develop a panel of blood-based diagnostic biomarkers consisting of
      circulating microRNAs for the detection of pancreatic cancer at an early stage.
      METHODS: Blood-based circulating microRNAs were profiled by high throughput
      screening using microarray analysis, comparing differential expression between
      early stage pancreatic cancer patients (n = 8) and healthy controls (n = 11). A
      panel of candidate microRNAs was generated based on the microarray signature
      profiling, including unsupervised clustering and statistical analysis of
      differential expression levels, and findings from the published literature. The
      selected candidate microRNAs were then confirmed using TaqMan real-time
      quantitative reverse transcription polymerase chain reaction (RT-qPCR) to further
      narrow down to a three-microRNA diagnostic panel. The three-microRNA diagnostic
      panel was validated with independent experimental procedures and instrumentation
      of RT-qPCR at an independent venue with a new cohort of cancer patients (n = 11),
      healthy controls (n = 11), and a group of high risk controls (n = 11). Receiver
      operating characteristic curve analysis was performed to assess the diagnostic
      capability of the three-microRNA panel. RESULTS: In the initial high throughput
      screening, 1220 known human microRNAs were screened for differential expression
      in pancreatic cancer patients versus controls. A subset of 42 microRNAs was then
      generated based on this data analysis and current published literature. Eight
      microRNAs were selected from the list of 42 targets for confirmation study, and
      three-microRNAs, miR-642b, miR-885-5p, and miR-22, were confirmed to show
      consistent expression between microarray and RT-qPCR. These three microRNAs were
      then validated and evaluated as a diagnostic panel with a new cohort of patients
      and controls and found to yield high sensitivity (91%) and specificity (91%) with
      an area under the curve of 0.97 (P < 0.001). Compared to the CA19-9 marker at
      73%, the three-microRNA panel has higher sensitivity although CA19-9 has higher
      specificity of 100%. CONCLUSION: The identified panel of three microRNA
      biomarkers can potentially be used as a diagnostic tool for early stage
      pancreatic cancer.

PMID- 24578784
TI  - Antidepressant fluoxetine and its potential against colon tumors.
AB  - Colon cancer is one of the most common tumors worldwide, with increasing
      incidence in developing countries. Patients treated with fluoxetine (FLX) have a
      reduced incidence of colon cancer, although there still remains great controversy
      about the nature of its effects. Here we explore the latest achievements related
      to FLX treatment and colon cancer. Moreover, we discuss new ideas about the
      mechanisms of the effects of FLX treatment in colon cancer. This leads to the
      hypothesis of FLX arresting colon tumor cells at the at G1 cell-cycle phase
      through a control of the tumor-related energy generation machinery. We believe
      that the potential of FLX to act against tumor metabolism warrants further
      investigation. 

PMID- 24578786
TI  - Paediatric computed tomography radiation dose: A review of the global dilemma.
AB  - Computed tomography (CT) has earned a well-deserved role in diagnostic radiology,
      producing cross-sectional and three-dimensional images which permit enhanced
      diagnosis of many pathogenic processes. The speed, versatility, accuracy, and non
      invasiveness of this procedure have resulted in a rapid increase in its use. CT
      imaging, however, delivers a substantially higher radiation dose than alternative
      imaging methodologies, particularly in children due to their smaller body
      dimensions. In addition, CT use in children produces an increased lifetime risk
      of cancer, as children's developing organs and tissues are inherently more
      vulnerable to cellular damage than those of adults. Though individual risks are
      small, the increasing use of CT scans in children make this an important public
      health problem. Various organizations have recommended measures to minimize
      unnecessary exposures to radiation through CT scanning. These include elimination
      of multiple or medically unnecessary scans, development of patient-specific
      dosing guidelines, and use of alternative radiographic methodology wherever
      possible. Another important factor in excessive CT exposures, however, is a
      documented lack of awareness among medical practitioners of the doses involved in
      CT usage as well as its significant potential dangers. This review examines the
      effects of paediatric CT radiation, discusses the level of medical practitioner
      awareness of these effects, and offers recommendations on alternative diagnostic
      methods and practitioner education. 

PMID- 24578788
TI  - Renal hilar paraganglioma: A case report.
AB  - Paragangliomas are extra-adrenal pheochromocytomas that derive from chromaffin
      cells and arise along the sympathetic paraganglia in the body. In the majority of
      cases, they are secretory tumors and most commonly present with palpitations.
      Plasma metanephrines are the standard screening tests for making the diagnosis
      which is confirmed by pathology. Imaging plays a very important role in
      establishing the diagnosis. However, there is no specific feature on imaging for
      paragangliomas; the vascularity of the tumor should show as hyper-enhancing
      lesions but this is not always the case. The diagnostic value of PET is yet a
      matter of debate. We present a very rare case of a paraganglioma arising at the
      renal hilum, splaying the renal artery and vein and causing vascular compromise
      to the left kidney. The patient presented with an atypical presentation of
      unrelenting fever that was followed by acute colicky pain. Based on imaging and
      blood metanephrine levels, the diagnosis of paraganglioma was made. Resection of
      the tumor was achieved and the patient is now asymptomatic. 

PMID- 24578787
TI  - Management of hepatocellular carcinoma: The role of contrast-enhanced ultrasound.
AB  - Hepatocellular carcinoma (HCC) is the sixth most common neoplasm and the third
      cause of cancer death worldwide. Contrast enhanced ultrasound (CEUS) has been
      applied for more than ten years and plays increasingly important roles in the
      management of HCC. On the basis of the Guideline and Good Clinical Practice
      Recommendations for CEUS in the liver-update 2012 and related literature about
      the management of HCC, we summarize the main roles and applications of CEUS in
      the management of HCC, including HCC surveillance, diagnosis, CEUS-guided
      treatment, treatment response evaluation and follow-up. The diagnostic algorithm
      for HCC is also suggested. Meanwhile, the comparisons between CEUS and contrast
      enhanced computed tomography/magnetic resonance imaging (CECT/CEMRI) in these
      areas are made. Although CEUS is subject to the same limitation as ordinary US
      and is inferior to CECT/CEMRI in some aspects, CEUS has proved to be of great
      value in the management of HCC with inherent advantages, such as sufficient high
      safety profile making it suitable for patients with renal failure or allergic to
      iodine, absence of radiation, easy reproducibility and high temporal resolution.
      The tremendous application of CEUS to the diagnosis and treatment of HCC provides
      more opportunities for patients with HCC diagnosed at different stages. 

PMID- 24578789
TI  - Treatment of metastatic liver tumors using stereotactic ablative radiotherapy.
AB  - The prognosis of patients with metastatic liver disease remains dismal with a
      median survival of only 6-12 mo. As 80%-90% of patients are not candidates for
      surgical therapy, there is a need for effective non-surgical therapies that would
      improve outcomes in these patients. The body of evidence related to the use of
      stereotactic ablative radiotherapy (SABR) in metastatic liver disease has
      substantially grown and evolved over the past decade. This review summarizes the
      current evidence supporting liver SABR with particular attention given to patient
      selection, target delineation, organ at risk dose volume constraints, response
      evaluation imaging and the various SABR techniques for delivering ablative
      radiotherapy to the liver. Even though it is unclear what dose-fractionation
      scheme, delivery system, concomitant therapy or patient selection strategy yields
      the optimum liver SABR outcomes, clear and growing evidence is available that
      SABR is a safe and effective therapy for the treatment of oligometastatic liver
      disease. 

PMID- 24578790
TI  - A spontaneous strangulated transomental hernia: Prospective and retrospective
      multi-detector computed tomography findings.
AB  - Transomental hernias are among the rarest type of all internal hernias which
      overall account for less than 6% of small bowel obstructions. Most transomental
      hernias occurring in adults are either iatrogenic or post-traumatic. More rarely,
      a spontaneous herniation of small bowel loops may result from senile atrophy of
      the omentum. We report a case of an 86-year-old male who presented with signs and
      symptoms of small bowel obstruction but had no past surgical or traumatic
      abdominal history. At contrast-enhanced multi-detector row computed tomography
      (CT), a cluster of fluid-filled dilated small bowel loops could be appreciated in
      the left flank, with associated signs of bowel wall ischemia. Swirling of the
      mesenteric vessels could also be appreciated and CT findings were prospectively
      considered consistent with a strangulated small bowel volvulus. At laparotomy, no
      derotation had to be performed but up to 100 cm of gangrenous small bowel loops
      had to be resected because of a transomental hernia through a small defect in the
      left part of the greater omentum. Retrospective reading of CT images was
      performed and findings suggestive of transomental herniation could then be
      appreciated. 

PMID- 24578791
TI  - Assessment of Developmental Toxicants using Human Embryonic Stem Cells.
AB  - Embryonic stem (ES) cells have potential for use in evaluation of developmental
      toxicity because they are generated in large numbers and differentiate into three
      germ layers following formation of embryoid bodies (EBs). In earlier study,
      embryonic stem cell test (EST) was established for assessment of the embryotoxic
      potential of compounds. Using EBs indicating the onset of differentiation of
      mouse ES cells, many toxicologists have refined the developmental toxicity of a
      variety of compounds. However, due to some limitation of the EST method resulting
      from species-specific differences between humans and mouse, it is an incomplete
      approach. In this regard, we examined the effects of several developmental toxic
      chemicals on formation of EBs using human ES cells. Although human ES cells are
      fastidious in culture and differentiation, we concluded that the relevancy of our
      experimental method is more accurate than that of EST using mouse ES cells. These
      types of studies could extend our understanding of how human ES cells could be
      used for monitoring developmental toxicity and its relevance in relation to its
      differentiation progress. In addition, this concept will be used as a model
      system for screening for developmental toxicity of various chemicals. This
      article might update new information about the usage of embryonic stem cells in
      the context of their possible ability in the toxicological fields. 

PMID- 24578792
TI  - Anti-cancer Effect and Underlying Mechanism(s) of Kaempferol, a Phytoestrogen, on
      the Regulation of Apoptosis in Diverse Cancer Cell Models.
AB  - Phytoestrogens exist in edible compounds commonly found in fruits or plants. For
      long times, phytoestrogens have been used for therapeutic treatments against
      human diseases, and they can be promising ingredients for future pharmacological
      industries. Kaempferol is a yellow compound found in grapes, broccoli and yellow
      fruits, which is one of flavonoid as phytoestrogens. Kaempferol has been
      suggested to have an antioxidant and anti-inflammatory effect. In past decades,
      many studies have been performed to examine anti-toxicological role(s) of
      kaempferol against human cancers. It has been shown that kaempferol may be
      involved in the regulations of cell cycle, metastasis, angiogenesis and apoptosis
      in various cancer cell types. Among them, there have been a few of the studies to
      examine a relationship between kaempferol and apoptosis. Thus, in this review, we
      highlight the effect(s) of kaempferol on the regulation of apoptosis in diverse
      cancer cell models. This could be a forecast in regard to use of kaempferol as
      promising treatment against human diseases. 

PMID- 24578793
TI  - Mercury induced the Accumulation of Amyloid Beta (Abeta) in PC12 Cells: The Role
      of Production and Degradation of Abeta.
AB  - Extracellular accumulation of amyloid beta protein (Abeta) plays a central role
      in Alzheimer's disease (AD). Some metals, such as copper, lead, and aluminum can
      affect the Abeta accumulation in the brain. However, the effect of mercury on
      Abeta accumulation in the brain is not clear. Thus, this study was proposed to
      estimate whether mercury concentration affects Abeta accumulation in PC12 cells.
      We treated 10, 100, and 1000 nM HgCl2 (Hg) or CH3HgCl2 (MeHg) for 48 hr in PC12
      cells. After treatment, Abeta40 in culture medium increased in a dose- and time
      dependent manner. Hg and MeHg increased amyloid precursor protein (APP), which is
      related to Abeta production. Neprilysin (NEP) levels in PC12 cells were decreased
      by Hg and MeHg treatment. These results suggested that Hg induced Abeta
      accumulation through APP overproduction and reduction of NEP. 

PMID- 24578794
TI  - Action Mechanism of Chamaecyparis obtusa Oil on Hair Growth.
AB  - This study was carried out to examine the action mechanism of Chamaecyparis
      obtusa oil (CO) on hair growth in C57BL/6 mice. For alkaline phosphatase (ALP)
      and gamma-glutamyl transpeptidase (gamma-GT) activities in the skin tissue, at
      week 4, the 3% minoxidil (MXD) and 3% CO treatment groups showed an ALP activity
      that was significantly higher by 85% (p < 0.001) and 48% (p < 0.05) and an gamma
      GT activity that was significantly higher by 294% (p < 0.01) and 254% (p < 0.05)
      respectively, as compared to the saline (SA) treatment group. For insulin-like
      growth factor-1 (IGF-1) mRNA expression in the skin tissue, at week 4, the MXD
      and CO groups showed a significantly higher expression by 204% (p < 0.05) and
      426% (p < 0.01) respectively, as compared to the SA group. At week 4, vascular
      endothelial growth factor (VEGF) expression in the MXD and CO groups showed a
      significantly higher expression by 74% and 96% (p < 0.05) respectively, however,
      epidermal growth factor (EGF) expression in the MXD and CO groups showed a
      significantly lower expression by 66% and 61% (p < 0.05) respectively, as
      compared to the SA group. Stem cell factor (SCF) expression in the MXD and CO
      groups was observed by immunohistochemistry as significant in a part of the bulge
      around the hair follicle and in a part of the basal layer of the epidermis.
      Taking all the results together, on the basis of effects on ALP and gamma-GT
      activity, and the expression of IGF-1, VEGF and SCF, which are related to the
      promotion of hair growth, it can be concluded that CO induced a proliferation and
      division of hair follicle cells and maintained the anagen phase. Because EGF
      expression was decreased significantly, CO could delay the transition to the
      catagen phase. 

PMID- 24578795
TI  - Genotoxicity Assessment of Erythritol by Using Short-term Assay.
AB  - Erythritol is a sugar alcohol that is widely used as a natural sugar substitute.
      Thus, the safety of its usage is very important. In the present study, short-term
      genotoxicity assays were conducted to evaluate the potential genotoxic effects of
      erythritol. According to the OECD test guidelines, the maximum test dose was
      5,000 MUg/plate in bacterial reverse mutation tests, 5,000 MUg/ml in cell-based
      assays, and 5,000 mg/kg for in vivo testing. An Ames test did not reveal any
      positive results. No clastogenicity was observed in a chromosomal aberration test
      with CHL cells or an in vitro micronucleus test with L5178Y tk (+/-) cells.
      Erythritol induced a marginal increase of DNA damage at two high doses by 24 hr
      of exposure in a comet assay using L5178Y tk (+/-) cells. Additionally, in vivo
      micronucleus tests clearly demonstrated that oral administration of erythritol
      did not induce micronuclei formation of the bone marrow cells of male ICR mice.
      Taken together, our results indicate that erythritol is not mutagenic to
      bacterial cells and does not cause chromosomal damage in mammalian cells either
      in vitro or in vivo. 

PMID- 24578796
TI  - Cytotoxic Activity from Curcuma zedoaria Through Mitochondrial Activation on
      Ovarian Cancer Cells.
AB  - alpha-Curcumene is one of the physiologically active components of Curcuma
      zedoaria, which is believed to perform anti-tumor activities, the mechanisms of
      which are poorly understood. In the present study, we investigated the mechanism
      of the apoptotic effect of alpha-curcumene on the growth of human overian cancer,
      SiHa cells. Upon treatment with alpha-curcumene, cell viability of SiHa cells was
      inhibited > 73% for 48 h incubation. alpha-Curcumene treatment showed a
      characteristic nucleosomal DNA fragmentation pattern and the percentage of sub
      diploid cells was increased in a concentration-dependent manner, hallmark
      features of apoptosis. Mitochondrial cytochrome c activation and an in vitro
      caspase-3 activity assay demonstrated that the activation of caspases accompanies
      the apoptotic effect of alpha-curcumene, which mediates cell death. These results
      suggest that the apoptotic effect of alpha-curcumene on SiHa cells may converge
      caspase-3 activation through the release of mitochondrial cytochrome c. 

PMID- 24578797
TI  - Evaluation of general toxicity and genotoxicity of the silkworm extract powder.
AB  - The silkworm extract powder contain 1-deoxynojirimycin (DNJ), a potent alpha
      glycosidase inhibitor, has therapeutic potency against diabetes mellitus.
      Therefore, natural products containing DNJ from mulberry leaves and silkworm are
      consumed as health functional food. The present study was performed to evaluate
      the safety of the silkworm extract powder, a health food which containing the
      DNJ. The repeated toxicity studies and gentic toxicity studies of the silkworm
      extract powder were performed to obtain the data for new functional food approval
      in MFDS. The safety was evaluated by a single-dose oral toxicity study and a 90
      day repeated-dose oral toxicity study in Sprague-Dawley rats. The silkworm
      extract powder was also evaluated for its mutagenic potential in a battery of
      genetic toxicity test: in vitro bacterial reverse mutation assay, in vitro
      chromosomal aberration test, and in vivo mouse bone marrow micronucleus assay.
      The results of the genetic toxicology assays were negative in all of the assays.
      The approximate lethal dose in single oral dose toxicity study was considered to
      be higher than 5000 mg/kg in rats. In the 90 day study, the dose levels were wet
      at 0, 500, 1000, 2000 mg/kg/day, and 10 animals/sex/dose were treated with oral
      gavage. The parameters that were monitored were clinical signs, body weights,
      food and water consumptions, ophthalmic examination, urinalysis, hematology,
      serum biochemistry, necropsy findings, organ weights, and histopathological
      examination. No adverse effects were observed after the 90 day administration of
      the silkworm extract powder. The No-Observed-Adverse-Effect-Level (NOAEL) of
      silkworm extract powder in the 90 day study was 2000 mg/kg/day in both sexes, and
      no target organ was identified. 

PMID- 24578798
TI  - Evaluation of the Mutagenic Properties of Two Lignans from Acanthopanax koreanum
      Nakai.
AB  - Acanthopanax koreanum Nakai, a well known traditional herb grown in Jeju Island,
      South of Korea, has been used as a tonic and sedative agent, as well as in the
      treatment of diabetes and immune diseases. Mutagenicity of two lignans,
      syringaresinol and tortoside A isolated from A. koreanum, was assessed using
      Salmonella/microsome (Ames) test. Tester strains used were Salmonella typhimurium
      TA98, TA100, TA1535, and Escherichia coli WP2uvrA. The mutagenic activity was
      determined both in the absence or presence of S9 mixture. As a result, tortoside
      A did not cause any increase in the number of his(+) revertants in S. typhimurium
      and E. coli WP2uvrA strains in the presence or absence of S9 mix, compared to the
      controls. Similarly, low concentrations of syringaresinol (750 and 1,500
      MUg/plate) did not show any mutagenic properties in all bacterial strains, in the
      presence or absence of S9 mixture. However, in the high concentration of
      syringaresinol (3,000 MUg/plate), the number of revertants were increased in
      TA1535 strains, in the absence of S9 metabolic activation. Therefore, in vivo
      experiments such as comet assay are needed to further determine the
      genotoxic/carciogenic potential of syringaresinol isolated from A. koreanum. 

PMID- 24578799
TI  - Subacute oral toxicity study of korean red ginseng extract in sprague-dawley
      rats.
AB  - Ginseng is a well-known traditional medicine used in Asian countries for several
      thousand years, and it is currently applied to medicine, cosmetics, and
      nutritional supplements due to its many healing and energygiving properties. It
      is well demonstrated that ginsenosides, the main ingredient of ginseng, produce a
      variety of pharmacological and therapeutic effects on central nerve system (CNS)
      disorders, cardiovascular disease, endocrine secretions, aging, and immune
      function. Korean red ginseng extract is a dietary supplement containing
      ginsenoside Rb1 and ginsenoside Rg1 extracted from Panax ginseng. While the
      pharmacokinetics and bioavailability of the extract have been well established,
      its toxicological properties remain obscure. Thus, four-week oral toxicity
      studies in rats were conducted to investigate whether Korean red ginseng extract
      could have a potential toxicity to humans. The test article was administered once
      daily by oral gavage to four groups of male and female Sprague-Dawley (SD) rats
      at dose levels of 0, 500, 1,000, and 2,000 mg/kg/day for four weeks. Neither
      deaths nor clinical symptoms were observed in any group during the experiment.
      Furthermore, no abnormalities in body weight, food consumption, ophthalmology,
      urinalysis, hematology, serum biochemistry, gross findings, organ weights, or
      histopathology were revealed related to the administration of the test article in
      either sex of any dosed group. Therefore, a target organ was not determined in
      this study, and the no observed adverse effect level (NOAEL) of Korean red
      ginseng extract was established to be 2,000 mg/kg/day. 

PMID- 24578800
TI  - Real-time Assay of Toxic Lead in In Vivo Living Plant Tissue.
AB  - A method of detecting lead was developed using square wave anodic stripping
      voltammetry (SWASV) with DNA-carbon nanotube paste electrode (CNTPE). The results
      indicated a sensitive oxidation peak current of lead on the DNA-CNTPE. The curves
      were obtained within a concentration range of 50 ngL(-1)-20 mgL(-1) with
      preconcentration time of 100, 200, and 400 sec at the concentration of mgL(-1),
      MUgL(-1), and ngL(-1), respectively. The observed relative standard deviation was
      0.101% (n = 12) in the lead concentration of 30.0 MUgL(-1) under optimum
      conditions. The low detection limit (S/N) was pegged at 8 ngL(-1) (2.6 * 10(-8)
      M). Results showed that the developed method can be used in real-time assay in
      vivo without requiring any pretreatment and pharmaceutical samples, and food
      samples, as well as other materials requiring water source contamination
      analyses. 

PMID- 24578801
TI  - Genetic dysbiosis: the role of microbial insults in chronic inflammatory
      diseases.
AB  - Thousands of bacterial phylotypes colonise the human body and the host response
      to this bacterial challenge greatly influences our state of health or disease.
      The concept of infectogenomics highlights the importance of host genetic factors
      in determining the composition of human microbial biofilms and the response to
      this microbial challenge. We hereby introduce the term 'genetic dysbiosis' to
      highlight the role of human genetic variants affecting microbial recognition and
      host response in creating an environment conducive to changes in the normal
      microbiota. Such changes can, in turn, predispose to, and influence, diseases
      such as: cancer, inflammatory bowel disease, rheumatoid arthritis, psoriasis,
      bacterial vaginosis and periodontitis. This review presents the state of the
      evidence on host genetic factors affecting dysbiosis and microbial misrecognition
      (i.e. an aberrant response to the normal microbiota) and highlights the need for
      further research in this area. 

PMID- 24578803
TI  - High-intensity focused ultrasound as salvage therapy for patients with recurrent
      prostate cancer after radiotherapy.
AB  - PURPOSE: To evaluate the oncologic outcomes and postoperative complications of
      high-intensity focused ultrasound (HIFU) as a salvage therapy after external-beam
      radiotherapy (EBRT) failure in patients with prostate cancer. MATERIALS AND
      METHODS: Between February 2002 and August 2010, we retrospectively reviewed the
      medical records of all patients who underwent salvage HIFU for transrectal
      ultrasound-guided, biopsy-proven locally recurred prostate cancer after EBRT
      failure (by ASTRO definition: prostate-specific antigen [PSA] failure after three
      consecutive PSA increases after a nadir, with the date of failure as the point
      halfway between the nadir date and the first increase or any increase great
      enough to provoke initiation of therapy). All patients underwent prostate
      magnetic resonance imaging and bone scintigraphy and had no evidence of distant
      metastasis. Biochemical recurrence (BCR) was defined according to the Stuttgart
      definition (PSA nadir plus 1.2 ng/mL). RESULTS: A total of 13 patients with a
      median age of 68 years (range, 60-76 years) were included. The median pre-EBRT
      PSA was 21.12 ng/mL, the pre-HIFU PSA was 4.63 ng/mL, and the period of salvage
      HIFU after EBRT was 32.7 months. The median follow-up after salvage HIFU was 44.5
      months. The overall BCR-free rate was 53.8%. In the univariate analysis,
      predictive factors for BCR after salvage HIFU were higher pre-EBRT PSA (p=0.037),
      pre-HIFU PSA (p=0.015), and short time to nadir (p=0.036). In the multivariate
      analysis, there were no significant predictive factors for BCR. The complication
      rate requiring intervention was 38.5%. CONCLUSIONS: Salvage HIFU for prostate
      cancer provides effective oncologic outcomes for local recurrence after EBRT
      failure. However, salvage HIFU had a relatively high rate of complications.

PMID- 24578804
TI  - Factors Influencing the Operative Approach to Renal Tumors: Analyses According to
      RENAL Nephrometry Scores.
AB  - PURPOSE: To evaluate the relationship between RENAL nephrometry score (RNS) and
      operative approach for renal masses. MATERIALS AND METHODS: This study included
      206 consecutive patients who underwent renal tumor surgery between January 2008
      and October 2012. We divided the patients into four groups by surgical approach:
      open radical nephrectomy (ORN, 53 patients), laparoscopic radical nephrectomy
      (LRN, 83 patients), open partial nephrectomy (OPN, 31 patients), and laparoscopic
      partial nephrectomy (LPN, 39 patients). We retrospectively assessed the RNS for
      each surgery group and evaluated the relationship between this score and
      operative approach. RESULTS: The mean RNSs of the ORN, LRN, OPN, and LPN groups
      were 9.75, 8.35, 6.72, and 5.76, respectively. When the RNS was analyzed
      according to nephron-sparing, the mean RNSs of the RN groups (ORN and LRN) and
      the PN groups (OPN and LPN) were significantly different (8.89 and 6.09,
      respectively; p<0.001). All the individual components of the RNS were
      significantly different between RN and PN. In the RN groups, the criteria for
      open versus laparoscopic surgery were based on tumor size ('R' score=2.43 for
      open, 1.54 for laparoscopic, p<0.001) and tumor location relative to the polar
      line ('L' score=2.55 for open, 2.09 for laparoscopic, p=0.006). In the PN groups,
      the criteria for open or laparoscopic surgery were based only on
      exophytic/endophytic property ('E' score=1.87 for open, 1.41 for laparoscopic,
      p=0.046). CONCLUSIONS: The RNS was significantly different in all surgery groups.
      The decision to take a laparoscopic approach was primarily influenced by the R
      and L scores for RN and by the E score for PN.

PMID- 24578802
TI  - Neural mechanisms underlying lower urinary tract dysfunction.
AB  - This article summarizes anatomical, neurophysiological, and pharmacological
      studies in humans and animals to provide insights into the neural circuitry and
      neurotransmitter mechanisms controlling the lower urinary tract and alterations
      in these mechanisms in lower urinary tract dysfunction. The functions of the
      lower urinary tract, to store and periodically release urine, are dependent on
      the activity of smooth and striated muscles in the bladder, urethra, and external
      urethral sphincter. During urine storage, the outlet is closed and the bladder
      smooth muscle is quiescent. When bladder volume reaches the micturition
      threshold, activation of a micturition center in the dorsolateral pons (the
      pontine micturition center) induces a bladder contraction and a reciprocal
      relaxation of the urethra, leading to bladder emptying. During voiding, sacral
      parasympathetic (pelvic) nerves provide an excitatory input (cholinergic and
      purinergic) to the bladder and inhibitory input (nitrergic) to the urethra. These
      peripheral systems are integrated by excitatory and inhibitory regulation at the
      levels of the spinal cord and the brain. Therefore, injury or diseases of the
      nervous system, as well as disorders of the peripheral organs, can produce lower
      urinary tract dysfunction, leading to lower urinary tract symptoms, including
      both storage and voiding symptoms, and pelvic pain. Neuroplasticity underlying
      pathological changes in lower urinary tract function is discussed. 

PMID- 24578805
TI  - Preoperative erythropoietin administration in patients with prostate cancer
      undergoing radical prostatectomy without transfusion.
AB  - PURPOSE: In this study, we administered erythropoietin preoperatively to patients
      who underwent open radical prostatectomy without transfusion to increase their
      hemoglobin levels and investigated the efficacy of this procedure. MATERIALS AND
      METHODS: We evaluated 62 patients who underwent open radical prostatectomy
      performed by the same surgeon between June 2005 and January 2011. The 22 patients
      who refused transfusion were assigned to group 1; the patients who accepted
      transfusion were assigned to group 2. Before surgery, we administered
      erythropoietin beta to group 1 patients whose hemoglobin levels were <12 g/dL and
      retrospectively compared the clinical data of the two groups. We used the t-test
      and the chi-square test for statistical analysis. RESULTS: Mean preoperative
      hemoglobin levels in group 1 after erythropoietin administration (14.5 g/dL) were
      significantly higher than those in group 2 (13.59 g/dL, p=0.003). Moreover, the
      difference in the mean hemoglobin levels before and after surgery for group 1
      patients (3.55 g/dL) significantly exceeded that for group 2 patients (2.08 g/dL,
      p=0.000). Additional analysis revealed no statistically significant differences
      in perioperative complications between the groups. CONCLUSIONS: Preoperative
      erythropoietin administration increased the safety margin of hemoglobin levels,
      and this strategy worked sufficiently well in our experience.

PMID- 24578806
TI  - Sedoanalgesia with midazolam and fentanyl citrate controls probe pain during
      prostate biopsy by transrectal ultrasound.
AB  - PURPOSE: To assess the pain intensity of patients administered midazolam and
      fentanyl citrate before undergoing transrectal ultrasound-guided prostate biopsy.
      MATERIALS AND METHODS: This was a study in patients with different indications
      for prostate biopsy in whom 5 mg of midazolam and 50 ug of fentanyl citrate was
      administered intravenously 3 minutes before the procedure. After biopsy, pain was
      assessed by use of a visual analogue scale (VAS) in three stages: VAS 1, during
      probe introduction; VAS 2, during needle penetration into prostate tissue; and
      VAS 3, in the weeks following the exam. Pain intensity at these different times
      was tested with stratification by age, race, education, prostate volume,
      rebiopsy, and anxiety before biopsy. Pain was ranked according to the following
      scores: 0 (no pain), 1-3 (mild pain), 4-7 (moderate pain), and 8-10 (severe
      pain). Statistical analysis was performed by using Kruskal-Wallis and Wilcoxon
      two-tailed tests with a significance of 5%. RESULTS: Pain intensity was not
      influenced by any risk factors. The mean VAS 1 score was 1.95+/-1.98, the mean
      VAS 2 score was 2.73+/-2.55, and the mean VAS 3 score was 0.3+/-0.9, showing
      greater pain at the time of needle penetration than in other situations (VAS
      2>VAS 1>VAS 3, p=0.0013, p=0.0001, respectively). Seventy-five percent of
      patients reported a VAS pain scale of less than 3.1 or mild pain. CONCLUSIONS:
      Intravenous sedation and analgesia with midazolam and fentanyl citrate is a good
      method for reducing pain caused by prostate biopsy, even during probe insertion.

PMID- 24578807
TI  - The Efficacy and Safety of Tadalafil 5 mg Once Daily in the Treatment of Erectile
      Dysfunction After Robot-Assisted Laparoscopic Radical Prostatectomy: 1-Year
      Follow-up.
AB  - PURPOSE: To evaluate the efficacy and safety of tadalafil 5 mg once daily use in
      the treatment of erectile dysfunction (ED) after robot-assisted laparoscopic
      radical prostatectomy (RALP). MATERIALS AND METHODS: The study retrospectively
      evaluated 92 patients who underwent RALP at Dong-A University Hospital. The
      patients were surveyed by use of the abridged five-item version of the
      International Index of Erectile Function (IIEF-5) questionnaire, which was self
      administered before surgery and at 6 months and 1 year after surgery. The 92
      patients were classified into the tadalafil group (n=47) and the non-tadalafil
      group (n=45). Each group was then classified depending on the nerve-sparing (NS)
      procedure used: bilateral NS or unilateral NS. RESULTS: At 6 months, the total
      IIEF-5 scores of the tadalafil group and the non-tadalafil group were 10.0+/-3.4
      and 7.0+/-4.0, respectively. At 1 year, the total IIEF-5 score in the tadalafil
      group was significantly greater than that in the non-tadalafil group (13.2+/-5.6
      vs. 7.7+/-4.8, p<0.0001). Statistically significant improvements (p<0.05) were
      observed in the tadalafil group for all 5 domains of the IIEF-5 score, whereas in
      the non-tadalafil group there was no significant improvement in any of the
      domains at 1 year. The reported side effects were flushing (8.5%, n=4), headache
      (4.3%, n=2), and dizziness (2.1%, n=1). CONCLUSIONS: In ED patients after NS
      RALP, a once-daily dose of tadalafil 5 mg was well tolerated and significantly
      improved EF compared with that in the non-tadalafil group.

PMID- 24578808
TI  - Comparison of Non-contrast-Enhanced Computed Tomography and Intravenous Pyelogram
      for Detection of Patients With Urinary Calculi.
AB  - PURPOSE: The aim of this study was to investigate the changing pattern in the use
      of intravenous pyelogram (IVP), conventional computed tomography (CT), and non
      contrast-enhanced computed tomography (NECT) for evaluation of patients with
      acute flank pain. MATERIALS AND METHODS: We retrospectively reviewed the medical
      records of 2,180 patients with acute flank pain who had visited Bundang Jesaeng
      General Hospital between January 2008 and December 2012 and analyzed the use of
      IVP, conventional CT, and NECT for these patients. RESULTS: During the study
      period there was a significant increase in NECT use (p<0.001) and a significant
      decrease in IVP use (p<0.001). Conventional CT use was also increased
      significantly (p=0.001). During this time the proportion of patients with acute
      flank pain who were diagnosed with urinary calculi did not change significantly
      (p=0.971). CONCLUSIONS: There was a great shift in the use of imaging study from
      IVP to NECT between 2008 and 2012 for patients with acute flank pain.

PMID- 24578809
TI  - Long-term Outcome of the Readjustable Sling Procedure for Female Stress Urinary
      Incontinence With Intrinsic Sphincter Deficiency or Recurrence.
AB  - PURPOSE: We evaluated the long-term outcome of a readjustable midurethral sling
      system (Remeex) in the treatment of recurrence of stress urinary incontinence
      (SUI) after surgical treatment or SUI with intrinsic sphincter deficiency (ISD).
      MATERIALS AND METHODS: This study included 19 patients who underwent the Remeex
      procedure with a mean of 45.6 months of follow-up. The patients had responded to
      a telephone questionnaire. Thirteen patients had ISD, four patients had SUI
      recurrence, and two patients had both. The questionnaire included subjective cure
      and satisfaction surveys and also recommended surgery to some patients. RESULTS:
      The mean patient age was 69.1 years (range, 50-85 years), the mean parity was
      2.79 times (range, 2-5 times), and the mean follow-up period was 45.6 months
      (range, 21-72 months). The long-term follow-up cure rate was 79%, the improvement
      rate was 21%, and the fail rate was 0%. The long-term follow-up "very
      satisfactory" rate was 26.3%, the "satisfactory" rate was 73.7%, and the "usual"
      and "unsatisfactory" rates were both 0%. In addition to these results, 16
      patients (84.2%) would recommend the Remeex procedure to other patients with SUI
      recurrence or ISD. After the procedure, four patients had urinary retention,
      three patients had difficulty emptying, and one patient had SUI recurrence.
      Furthermore, all of the patients subsequently endured sling readjustments.
      CONCLUSIONS: After long-term follow-up, the Remeex system showed good cure rates
      and subjective satisfaction rates that were similar to the results found at the 1
      year follow-up, and minimal complications were reported. Therefore, the Remeex
      system is effective in treating patients with SUI recurrence or ISD.

PMID- 24578810
TI  - Serotonin Transporter Promoter Region (5-HTTLPR) Polymorphism Is Not Associated
      With Paroxetine-Induced Ejaculation Delay in Dutch Men With Lifelong Premature
      Ejaculation.
AB  - PURPOSE: To investigate the association between the 5-HT-transporter-gene-linked
      promoter region (5-HTTLPR) polymorphism and 20-mg paroxetine-induced ejaculation
      delay in men with lifelong premature ejaculation (LPE). MATERIALS AND METHODS:
      This was a prospective study of 10 weeks of paroxetine treatment in 54 men with
      LPE. Intravaginal ejaculation latency time (IELT) was measured by stopwatch.
      Controls consisted of 92 Caucasian men. All men with LPE were genotyped for the 5
      HTTLPR polymorphism. Allele frequencies and genotypes of short (S) and long (L)
      variants of the polymorphism were compared between patients and controls.
      Associations between the LL, SL, and SS genotypes and fold increase of mean IELT
      were investigated. RESULTS: Of the 54 patients, 43 (79.6%) responded to 20-mg
      paroxetine treatment with an ejaculation delay, whereas 11 patients (20.4%) did
      not respond; 44%, 18%, and 18% of the patients showed a fold increase in mean
      IELT of 2-10, 10-20, and more than 20, respectively. Of the 54 men, 14 (25.9%)
      had the LL genotype, 29 (53.7%) had the SL genotype, and 11 (20.4%) had the SS
      genotype. In the 92 controls, the LL, SL, and SS genotypes were present in 27
      (29.3%), 41 (44.6%), and 24 (26.1%), respectively. No statistically significant
      differences were found in 5-HTTLPR allelic variations or in 5-HTTLPR gene
      variations. In all men treated with 20 mg paroxetine, analysis of variance of the
      natural logarithm of fold increase in the IELT showed no statistically
      significant difference according to genotype (p=0.83). CONCLUSIONS: The 5-HTTLPR
      polymorphism is not associated with daily 20-mg paroxetine treatment-induced
      ejaculation delay in men with LPE.

PMID- 24578811
TI  - The attitudes of infertile male patients toward the use of artificial
      insemination by donor: a korean regional survey.
AB  - PURPOSE: Infertile couples interested in nonspouse artificial insemination by
      donor (AID) not only require a thorough understanding of the medical procedure
      but also must scrutinize the effects it will have on family relationships,
      including those on the infant to be born. We conducted a series of surveys in
      couples with male infertility to collect information necessary for AID
      counseling. MATERIALS AND METHODS: A total of 384 cases with noncurable male
      infertility were enrolled in this inquiry survey. The questionnaire consisted of
      18 items that assessed demographic characteristics, background information
      concerning the choice to use AID, subjective experiences, long-term effects, and
      an overall evaluation. RESULTS: A total of 126 surveys were returned (32.8%). AID
      was first suggested by the husband in about half of the cases. The major reason
      for considering the procedure was to form a complete family. Two-thirds of the
      couples were anxious about the procedure, most often about possible congenital or
      acquired deformities in the infant. After the birth of the child, most couples
      were positive about their decision to have used AID. About half of the couples
      felt that the child was their own and expected not to tell the child about AID.
      Overall, about 50% of the couples were satisfied with the procedure. CONCLUSIONS:
      Those who underwent AID experienced various psychological effects, including
      anxiety about the child to be born. To overcome these problems, sufficient
      medical information and consultation about the process of selecting the donor and
      about AID procedures should be provided before the procedure is used.

PMID- 24578813
TI  - Translocation Renal Cell Carcinoma t(6;11)(p21;q12) and Sickle Cell Anemia: First
      Report and Review of the Literature.
AB  - Translocation renal cell carcinoma (RCC) is a family of rare tumors recently
      identified in the pediatric and young adult population. We report the first case
      of a young woman from French West Indies with sickle cell anemia who developed a
      translocation RCC t(6;11)(p21;q12). Usually people with the sickle cell condition
      are known to develop renal medullary carcinoma (RMC). To our knowledge, this is
      the first case described in the literature of a translocation RCC associated with
      sickle cell disease. Here we discuss the relation between translocation RCC, RMC,
      and sickle cell disease. 

PMID- 24578814
TI  - Primary mature cystic teratoma mimicking an adrenal mass in an adult male
      patient.
AB  - Teratomas are bizarre neoplasms derived from embryonic tissues that are typically
      found only in the gonadal and sacrococcygeal regions of adults. Primary
      retroperitoneal teratomas are rare and present challenging management options. We
      report a case of a unilateral primary retroperitoneal mature cystic teratoma
      mimicking an adrenal mass in a 54-year-old male patient. Complete resection of
      the adrenal mass was performed by the flank approach by using the 11th rib
      resection. Because of the risk of malignancy, follow-up radiographic studies were
      performed to ensure the oncologic efficacy of resection. The patient has been
      free of recurrence for longer than 12 months. 

PMID- 24578812
TI  - The Second-to-Fourth Digit Ratio in Cryptorchidism: A Case-Control Study.
AB  - PURPOSE: The homeobox (Hox) genes a and d controlling limb and genital
      development influence the digit ratio and the fetal production of testicular
      androgen, which may result in testicular descent in boys. To assess whether the
      digit ratio reflects disease status, we investigated the second and fourth finger
      lengths in children with cryptorchidism, in children with hydrocele as a disease
      control, and in healthy controls (boys and girls). MATERIALS AND METHODS: One
      hundred ninety-six children (46 with cryptorchidism, 50 with hydrocele, 50
      healthy boys, and 50 healthy girls) who were 6 to 23 months of age were
      prospectively enrolled. Digit lengths were measured by 2 investigators, and the
      mean value was recorded. RESULTS: The second-to-fourth digit ratios (2D:4Ds) of
      the left hand in the cryptorchidism group, hydrocele group, healthy boys, and
      healthy girls were 0.958, 0.956, 0.950, and 0.956, respectively. The 2D:4D values
      of the right hand were 0.946, 0.945, 0.952, and 0.969, respectively. The right
      and left 2D:4D ratios were not significantly different among groups. The 2D:4D of
      both hands was not related to age, weight, or height. CONCLUSIONS: According to
      these results, the 2D:4D was not significantly different in boys with
      cryptorchidism than in boys with hydrocele or in healthy controls (boys and
      girls) and failed to reflect disease conditions in the infant period.

PMID- 24578815
TI  - Periodontal dressing: a review article.
AB  - The purpose of this paper was to review the commercially available periodontal
      dressings, their physical and chemical properties, biocompatibility and
      therapeutic effects. Electronic search of scientific papers from 1956 to 2012 was
      carried out using PubMed, Scopus and Wiley InterScience search engines using the
      searched terms periodontal dressing, periodontal pack. Numerous in vitro and in
      vivo studies have evaluated various properties of periodontal dressings. Physical
      and chemical properties of dressings are directly related to their dimensional
      changes and adhesion properties. Their biocompatibility and therapeutic effect
      are among the other factors evaluated in the literature. Chlorhexidine is the
      most commonly used antibacterial agent in studies. In general, when comparing the
      advantages with the disadvantages, application of periodontal dressing seems to
      be beneficial. Numerous factors are involved in selection of an optimal dressing
      such as surgeon&rsquo;s intention, required time for the dressing to remain on
      the surgery site and its dimensional changes. 

PMID- 24578816
TI  - In Vitro Cytotoxicity Assessment of an Orthodontic Composite Containing Titanium
      dioxide Nano-particles.
AB  - Background and aims. Incorporation of nano-particles to orthodontic bonding
      systems has been considered to prevent enamel demineralization around appliances.
      This study investigated cytotoxicity of Transbond XT adhesive containing 1 wt%
      titanium dioxide (TiO2) nano-particles. Materials and methods. Ten composite
      disks were prepared from each of the conventional and TiO2-containg composites
      and aged for 1, 3, 5, 7 and 14 days in Dulbecco's Modified Eagle's Medium (DMEM).
      The extracts were obtained and exposed to culture media of human gingival
      fibroblasts (HGF) and mouse L929 fibroblasts. Cell viability was measured using
      the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay.
      Results. Both adhesives were moderately toxic for HGF cells on the first day of
      the experiment, but the TiO2-containing adhesive produced significantly lower
      toxicity than the pure adhesive (P<0.05). No significant differences were found
      in cell viability percentages between the two groups on the other days (P>0.05).
      There was a significant reduction in cell toxicity with increasing pre-incubation
      time (P<0.001). L929 cells showed similar toxicity trends, but lower sensitivity
      to detect cytotoxicity of dental composites. Conclusion. The orthodontic adhesive
      containing TiO2 nano-particles indicated comparable or even lower toxicity than
      its nano-particle-free counterpart, indicating that incorporation of 1 wt% TiO2
      nano-particles to the composite structure does not result in additional health
      hazards compared to that occurring with the pure adhesive. 

PMID- 24578817
TI  - The effects of composite resin types and debonding pliers on the amount of
      adhesive remnants and enamel damages: a stereomicroscopic evaluation.
AB  - Background and aims. This in vitro study was designed to evaluate the effect of
      composite resin types and orthodontic debonding pliers on the amount of adhesive
      remnants and enamel damages using a novel method of measurement. Materials and
      methods. 120 extracted human premolars were randomly divided into four groups (n
      = 30). The standard edgewise metallic brackets were bonded to the teeth with
      light-cured composite resin "Transbond XT" in the first and second groups, and No
      mix composite resin "Unite" in the third and fourth groups. Bracket debonding was
      carried out with Lift Off Debonding Instrument "LODI" (3M Unitek) in the first
      and third groups, and with Bracket Removing Pliers (Dentaurum) in the second and
      forth groups. yStereomicroscopic evaluation was performed by unbiased sterelogy.
      All teeth were evaluated for the amount of adhesive remnants and the number and
      length of enamel cracks. The obtained data on each step was analyzed by two-way
      ANOVA, chi-square, Wilcoxon, and Kruskal-Wallis. Results. Teeth in group 4 had
      the lowest adhesive remnants on the enamel surface (p < 0.01); and the highest
      increase in the number of enamel cracks (p < 0.01) among the groups. In addition,
      groups bonded with Unite showed the highest increase in the length of enamel
      cracks. Conclusion. Dentaurum debonding pliers with sheer-peel force, when used
      with the Unite adhesive (group 4), decreased the amount of adhesive remnants on
      the enamel surface while it increased enamel damages. 

PMID- 24578818
TI  - Remineralization of artificial caries in primary teeth by grape seed extract: an
      in vitro study.
AB  - Background and aims. Promoting remineralization is the ultimate goal of clinical
      prevention of caries lesion. The present in vitro study aimed to investigate the
      effect of grape seed extract (GSE) on artificial enamel caries in primary human
      teeth. Materials and methods. Seventeen human sound primary incisors were
      sectioned mesiodistally. The tooth slices were placed in a demineralizing
      solution for 96 hours at 37oC and 50% relative humidity to create lesions. The
      demineralized fragments of each tooth were randomly divided into two case
      (immersed in GSE solution in phosphate buffer for 8 days) and control (immersed
      in distilled water) groups. The samples were subsequently evaluated using a
      scanning electron microscope and a micro-hardness tester. Data were analyzed
      using independent t-test. Results. The mean +/- SD micro-hardness values for the
      case and control groups were 358.6+/-83.42 and 296.51+/- 69.41, respectively.
      Grape seed extract significantly increased the micro-hardness of the lesions
      (P=0.03). The morphology of GSE treated enamel was clearly different from that in
      the control group, and there were deposits of scaffolding insoluble complexes on
      the enamel surface. Conclusion. GSE enhanced the remineralization process of
      artificial enamel lesions of primary teeth, and thus, might be considered an
      effective natural agent in non-invasive dentistry. 

PMID- 24578819
TI  - Effect of Home Bleaching on Microleakage of Fiber-reinforced and Particle-filled
      Composite Resins.
AB  - Background and aims. Bleaching may exert some negative effects on existing
      composite resin restorations. The aim of this study was to evaluate the effect of
      home bleaching on microleakage of fiber-reinforced and particle-filled composite
      resins. Materials and methods. Ninety class V cavities (1.5*2*3 mm) were prepared
      on the buccal surfaces of 90 bovine teeth. The teeth were randomly divided into 6
      groups (n=15) and restored as follows: Groups 1 and 2 with Z100, groups 3 and 4
      with Z250, and groups 5 and 6 with Nulite F composite resins. All the specimens
      were thermocycled. Groups 1, 3 and 5 were selected as control groups (without
      bleaching) and the experimental groups 2, 4 and 6 were bleached with 22%
      carbamide peroxide gel. All the samples were immersed in 2% basic fuchsin dye for
      24 hours and then sectioned longitudinally. Dye penetration was evaluated under a
      stereomicroscope (*25), at both the gingival and incisal margins. Data were
      analyzed using Kruskal-Wallis, Mann-Whitney and Wilcoxon tests (a=0.05). Results.
      Statistical analyses revealed that bleaching gel increased microleakage only at
      gingival margins with Z250 (P=0.007). Moreover, the control groups showed a
      statistically significant difference in microleakage at their gingival margins.
      Nulite F had the maximum microleakage while Z250 showed the minimum (P=0.006).
      Conclusion. Microleakage of home-bleached restorations might be related to the
      type of composite resin used. 

PMID- 24578820
TI  - Evaluation of the Effect of Two Systemic Doses of HESA-A on Prevention of Induced
      Tongue Neoplasm in Rats.
AB  - Background and aims. The aim of the present study was to compare the inhibitory
      effects of two systemic doses of HESA-A on prevention of 4-NQO-induced tongue
      neoplasms in rats. This study evaluated weight and histopathological changes.
      Materials and methods. Forty-eight male Sprague Dawley rats were divided into
      four groups of A, B, C and D of each 12 rats. The rats in groups B to D received
      30 ppm of 4-Nitroquinoline-1-oxide (4-NQO) in drinking water for 12 weeks.  When
      feeding with 4-NQO was initiated, the rats in groups B and C received HESA-A at
      doses of 250 and 500 mg/kg, respectively, 3 times a week. Body weights were
      measured three times a week. At the end, the rats were euthanized and the tongue
      was removed. Histological evaluations for carcinogenesis were carried out under a
      light microscope. Results. The mean body weights of rats in groups B, C and D
      were significantly lower than that in group A (P < 0.05). There were no
      significant differences in weight changes between groups B, C and D. In the
      present study, after 12 weeks of treatment, Tongue specimens in groups B and C
      did not exhibit severe dysplastic changes; however, concurrent hyperplasia,
      without atypia and mild-to-moderate dysplastic changes were detected. These
      changes were significantly less than those in group D, with significant
      differences between group D and groups A, B and C (P<0.001, P<0.01 and P<0.05,
      respectively). Conclusion. HESA-A has dose-dependent inhibitory effects on the
      development of neoplasms of the tongue. 

PMID- 24578821
TI  - Correlation of histopathologic features with demographic, gross and radiographic
      findings in giant cell granulomas of the jaws.
AB  - Background and aims. The correlation between morphology of giant cells in
      peripheral granulomas of the jaws and the aggressive behavior of the lesion is
      unknown. This study investigated the correlation between the histopathologic
      features with demographic, gross and radiographic findings in giant cell
      granulomas. Materials and methods. In this analytical study, data from 23 cases
      of central giant cell granuloma (CGCG) and 42 cases of peripheral giant cell
      granuloma (PGCG) were analyzed, focusing on age, gender, location, and gross and
      radiographic features. For each patient, microscopic slides were assessed in
      terms of histologic features of giant cells and stroma. Results. No significant
      differences were found in the mean number of nuclei or the size of nuclei and
      giant cell distribution patterns between the jaws and genders in both lesions (P
      >0.05). Correlation between the mean number of nuclei and age was positively
      significant and correlation between the size of nuclei and age was negatively
      significant (P < 0.05). In addition, correlation between the mean number and size
      of nuclei and the size of the lesion was significant (P < 0.05). Correlation
      between stroma and aggressiveness of CGCGs was not statistically significant.
      Correlation between histopathologic features and radiographic findings was not
      statistically significant (P > 0.05). Conclusion. There were correlations between
      the mean number of nuclei per giant cell and the size of the lesion and age, and
      between the size of nuclei and size of the lesion. No relation was observed
      between histopathologic and radiographic features. 

PMID- 24578822
TI  - Detection of Helicobacter pylori in Oral Lesions.
AB  - Background and aims. Helicobacter pylori is a microaerophilic gram-negative
      spiral organism. It is recognized as the etiologic factor for peptic ulcers,
      gastric adenocarcinoma and gastric lymphoma. Recently, it has been isolated from
      dental plaque and the dorsum of the tongue. This study was designed to assess the
      association between H. pylori and oral lesions such as ulcerative/inflammatory
      lesions, squamous cell carcinoma (SCC) and primary lymphoma. Materials and
      methods. A total of 228 biopsies diagnosed as oral ulcerative/inflammatory
      lesions, oral squamous cell carcinoma (OSCC) and oral primary lymphoma were
      selected from the archives of the Pathology Department. Thirty-two samples that
      were diagnosed as being without any pathological changes were selected as the
      control group. All the paraffin blocks were cut for hematoxylin and eosin
      staining to confirm the diagnoses and then the samples were prepared for
      immunohistochemistry staining. Data were collected and analyzed. Results. Chi
      squared test showed significant differences between the frequency of H. pylori
      positivity in normal tissue and the lesions were examined (P=0.000). In addition,
      there was a statistically significant difference between the lesions examined
      (P=0.042). Chi-squared test showed significant differences between H. pylori
      positivity and different tissue types except inside the muscle layer as follows:
      in epithelium and in lamina propria (P=0.000), inside the blood vessels
      (P=0.003), inside the salivary gland duct (P=0.036), and muscle layer (P=0.122).
      Conclusion. There might be a relation between the presence of H. pylori and oral
      lesions. Therefore, early detection and eradication of H. pylori in high-risk
      patients are suggested. 

PMID- 24578823
TI  - A Comparison in Prevalence of Helicobacter pylori in the Gingival Crevicular
      Fluid from Subjects with Periodontitis and Healthy Individuals using Polymerase
      Chain Reaction.
AB  - Background and aims. The high prevalence of Helicobacter pylori among the
      microorganisms isolated from the oral environment brings up the question of
      whether oral cavity acts as a reservoir for this bacterium. The aim of the
      present study was to determine and compare the prevalence of H. pylori in
      gingival crevicular fluid (GCF) of patients with chronic periodontitis (CP) as an
      infectious disease and healthy subjects using polymerase chain reaction (PCR).
      Materials and methods. Periodontal examination was performed for all
      participants. Two sterilized paper points were inserted to the maximum depth of
      the periodontal pockets of selected teeth. The presence of H. pylori was
      determined by PCR. In the CP group, the severity of disease was defined as
      moderate or severe. Further, the frequency of Helicobacter pylori in GCF of each
      category, and the association between the presence of Helicobacter pylori in GCF
      and periodontitis were determined. Results. There was no statistically
      significant association between CP and the presence of H. pylori in the GCF (P =
      0.62), there was no significant correlation between the presence of H. pylori in
      the GCF and gender of the subjects (P = 0.28 in CP group and P = 0.25 in control
      group), and there was no significant correlation between the presence of H.
      pylori in the GCF and severity of periodontitis (P = 0.20). Conclusion. Oral
      cavity acts as a reservoir for H. pylori; however, the results do not show that
      H. pylori is involved in periodontal disease. 

PMID- 24578824
TI  - Horizontal root fracture accompanied by luxation of coronal fragment in a
      maxillary central incisor: a case report.
AB  - Root fracture injuries affect up to 7% of permanent teeth. This type of injury is
      rarely seen in teeth with open apices and depending on the fracture site, the
      prognosis is good. This case report describes a horizontal intra-alveolar root
      fracture in the middle third of a maxillary central incisor associated with an
      extrusive luxation of the coronal segment and its treatment in a 6-year-old girl.
      The patient was observed under a regular follow-up regime. After 2 years,
      clinical examination showed normal tooth color and position, with a positive
      response to the pulp test. 

PMID- 24578825
TI  - Clinical utility of serum sclerostin measurements.
AB  - Sclerostin is an osteocyte-secreted soluble antagonist of the Wnt/beta-catenin
      signaling pathway requisite for osteoblast development and activity. Efforts over
      the past several years have focused on unraveling the role of sclerostin in both
      normal physiological and pathological conditions. Sclerostin levels are
      undetectable in the serum of patients with sclerosteosis. In normal individuals,
      serum sclerostin levels are higher in males and increase in both sexes across the
      adult lifespan. Some, but not other, studies have demonstrated that higher serum
      sclerostin levels are associated with increased fracture risk, particularly when
      paired with lower bone mineral density. Levels of circulating sclerostin are
      highly correlated with bone marrow sclerostin levels. Sclerostin levels are
      inversely related to parathyroid hormone levels. Clinical conditions in which
      serum sclerostin levels have been measured include ankylosing spondylitis,
      chronic kidney disease, diabetes, fractures, hypercortisolism, multiple myeloma
      and spinal cord injury. Even within clearly defined clinical conditions, however,
      consistent changes in serum sclerostin levels have not always been seen. This may
      reflect differences in currently available commercial assays or sample sources
      (serum versus plasma), and suggests further study is needed before sclerostin
      measurements are introduced into routine clinical practice. Until such issues are
      resolved, measurement of sclerostin levels appears to be most useful for
      understanding the mechanisms by which osteocytes regulate bone turnover through
      the integration of hormonal, physical and pharmacological stimuli, rather than to
      guide clinical-care decisions. 

PMID- 24578826
TI  - Concerns on the growing use of lithium: the pros and cons.

PMID- 24578827
TI  - Rhazes, a genius physician in the diagnosis and treatment of nocturnal enuresis
      in medical history.
AB  - CONTEXT: Nocturnal enuresis has undoubtedly occurred since man's earliest days
      and the first references are found in the Ebers papyri of 1550 BC. The purpose of
      this study is to review of Rhazes opinion about diagnosis and treatment of
      nocturnal enuresis and compare his belief and clinical methods with modern
      medical practice. EVIDENCE ACQUISITION: In the review study we searched all
      available and reliable electronic and paper sources using appropriate keywords
      about the views of Rhazes, and compared them with recent medical evidence about
      diagnosis and treatment of nocturnal in medication. RESULTS: Our findings proved
      that Rhazes described the symptoms, signs, and the treatment of nocturnal
      enuresis in accordance with contemporary medicine. CONCLUSIONS: A review of
      opinion Rhazes and other ancient Islamic medical textbooks on nocturnal enuresis
      reveals that medical practice in those days was comparable to modern medicine yet
      avoiding the side effects that are commonly experienced with the modern medical
      approach.

PMID- 24578828
TI  - The comparative effects of atorvastatin and quince leaf extract on
      atherosclerosis.
AB  - BACKGROUND: This study investigates the ability of quince leaf extract to prevent
      progression of atherosclerosis and to determine the lipid-lowering effect of it.
      OBJECTIVES: This study suggested that quince leaf effects on progression of
      atherosclerosis, and performed comparison with atorvastatin as a standard
      medication. MATERIALS AND METHODS: The effect of 50mg/kg of the quince leaf
      extract on lipid profiles was assessed by measuring the levels of
      totalcholesterol, triglyceride, LDL, HDL, and liver enzymes (AST, ALT, and AP) in
      plasma and were evaluated the thickness of aortic plaques in the
      hypercholesterolemic rabbits after stopping. These assessments were performed
      using 0.5 mg/kg of atorvastatin. RESULTS: Oral administration of cholesterol for
      8 weeks resulted in a significant increase (P < 0.05) in plasma markers.
      Treatment with the extract at dose of 50 mg/kg and 0.5 mg/kg of atorvastatin not
      only were reduced lipid profile in plasma (P < 0.05) but also were increased HDL
      cholesterol levels. There were decrease (P = 0.04) in the liver enzymes in
      extract treated rabbits. However, plaque thickness had no significant difference
      in the aorta of treated rabbits compared with studied control. CONCLUSIONS: These
      results indicate the lipid-lowering effects of quince leaf similar to
      atorvastatin and it can probably serve as a new potential natural product for
      atherosclerosis treatment.

PMID- 24578829
TI  - Association of depression and anxiety with diabetes mellitus type 2 concerning
      some sociological factors.
AB  - BACKGROUND: Diabetes is a metabolic disorder with a high worldwide prevalence. It
      has been reported that diabetic patients are more prone to depression and
      anxiety. OBJECTIVES: This study aimed to evaluate the prevalence of depression
      and anxiety among diabetic patients with regards to some factors such as age,
      gender, level of education and occupational status. MATERIALS AND METHODS: One
      hundred and eighty four diabetic patients have participated in this study. To
      assess the severity of depression and anxiety Beck depression inventory and Beck
      anxiety inventory questionnaire were used respectively. Binary logistic
      regressions were used to analyze the data. RESULTS: The results of the present
      study have shown that 70.7% of the diabetic patients were suffered from
      depression. Besides, 69.6% of them were diagnosed with anxiety. According to the
      result, diabetes related depression is affected by sex (OR: 2.767), age (OR:
      2.222), level of education (OR: 4.145) and job status (OR: 3.901). It has been
      also resulted that gender (OR: 2.274), age (OR: 2.706) and Job Status (OR: 2.441)
      are the effective factors leading to anxiety. CONCLUSIONS: Depression and anxiety
      have higher prevalence among diabetic patients and some sociological factors such
      as age, gender, job and education are related to these psychological disorders.

PMID- 24578830
TI  - Evaluation of the Effects of Atorvastatin on the Treatment of Secondary Pulmonary
      Hypertension due to Chronic Obstructive Pulmonary Diseases: A Randomized
      Controlled Trial.
AB  - BACKGROUND: Since pulmonary hypertension (PH) in patients with chronic
      obstructive pulmonary diseases (COPD) causes poor prognosis and inflammatory
      process involved in PH, it is supposed that Statins with anti-inflammatory
      effects might be useful in the treatment of PH. OBJECTIVES: The aim of this study
      was to evaluate the influence of Atorvastatin on the treatment of pulmonary
      hypertension in patients with COPD. PATIENTS AND METHODS: A registered
      (IRCT201108257411N1), triple-blind, randomized controlled trial was performed in
      Rasoule Akram hospital, Tehran, from 2009 to 2011. Forty five patients with
      secondary pulmonary hypertension due to COPD were recruited and randomized to two
      groups receiving either Atorvastatin 40 mg/d or placebo in addition to their
      current treatment for 6 months. The outcomes including systolic pulmonary
      arterial hypertension (SPAH), cardiac output (CO), right ventricular size (RVS),
      CRP, 6 min walk distance test (6MWD), and spirometry parameters were measured
      after 6 months. RESULTS: Baseline characteristics were similar in both groups.
      After 6 months, pulmonary hypertension changed from 48.5 +/- 6.9 to 42.9 +/- 9.3
      mmHg for Atorvastatin users and from 49.7 +/- 11.4 to 48.2 +/- 14.6 mmHg for
      Placebo users (P = 0.19, CI - 13.57 - 2.89), 6MWD after 6 months was 339 +/- 155
      meters in case group versus 340 +/- 106 meters in control group (P = 0.98, CI -
      92.58 - 91.15). There were no significant changes in other outcomes including
      CRP, RVS, CO and spirometry parameters. CONCLUSIONS: Although we found a trend
      towards decreasing SPAH and improving 6MWD, no statistically significant shift
      were detected in our outcomes due to inadequate sample size.

PMID- 24578831
TI  - Perceived Barriers Affecting Access to Preventive Dental Services: Application of
      DEMATEL Method.
AB  - BACKGROUND: Identifying perceived access barriers to preventive dental services
      is one of the basic steps to improve the public health. OBJECTIVES: This study
      aimed to determine the perceived barriers affecting access to preventive dental
      services in one of Tehran dental clinics in 2012. PATIENTS AND METHODS: This
      research was a cross-sectional descriptive-analytical study conducted in one of
      Tehran dental clinics in 2012 using decision-making trial and evaluation
      laboratory (DEMATEL) method. The study sample included all patients (100
      patients) who had referred to the endodontic treatment department from 26 - 31
      May, 2012. The required data were collected using a questionnaire. Collected data
      were analyzed using SPSS 18.0 and MATLAB 7.9.0 SPSSS 18.0, as well as, some
      descriptive and analytical tests including Mean, Standard Deviation (SD), and
      Independent T- Test. RESULTS: The five determinants of cost, inconvenience, fear,
      organization, and patient-dentist relationship were determined as barriers to
      access to dental services among which the cost and patient-dentist relationship
      were identified as the first and last priorities with the coordinates (1.4 and
      1.4) and (1.25 and -0.65), respectively. CONCLUSIONS: High cost of dental care
      has led to not referring patients to the clinic. Oral health costs are too high;
      however insurance organizations have no commitment to support such services.
      Policymakers, administrators, and insurance organizations have a major role in
      improving access to dental services. These decision-makers in making their
      policies can provide the required financial resources, shift the available
      resources towards preventive care and periodic checkups, and consider providing
      proper and sufficient places for dental care facilities.

PMID- 24578832
TI  - Perceived social support among people with physical disability.
AB  - BACKGROUND: Disability is more based on social, rather than medical aspects. Lack
      of attention and social support may impact on participation of people with
      physical disability in various aspects and their return to normal life in the
      society. OBJECTIVES: This study was conducted to determine perceived social
      support and related factors among physically disabled in the city of Tehran.
      PATIENTS AND METHODS: This cross-sectional study by using simple random sampling
      was conducted on 136 people with physically disabled who were covered by Welfare
      Organization of Tehran. The Norbeck social support questionnaire was used
      .Multiple linear regression analysis with the backward method was used to
      identify the adjusted association between perceived social support as dependent
      variable and demographic variables as independent variables. RESULTS: The present
      sample comprised of 68 (50%) male and 68 (50%) female with the mean age of 33 (SD
      = 8.9) years. Based on the results, mean of functional support was 135. 57 (SD =
      98.77) and mean of structural support was 77.37 (SD = 52.37). Regression analysis
      model, demonstrates that variables of age and marital status remained in the
      model as significant predictors of functional support (P = 0.003, P = 0.004,
      respectively) and structural support (P = 0.002, P = 0.006, respectively).
      CONCLUSIONS: Based on the results, participants in the study didn't have
      favorable status with respect to perceived social support (in all dimensions)
      from their social network members. While, social support as one of the social
      determinants of health, plays an important role in improving psychological
      conditions in people's lives; therefore, being aware of social support and
      designing effective interventions to improve it for the disabled is very
      important.

PMID- 24578833
TI  - Is Certolizumab Pegol Safe and Effective in the Treatment of Patients with
      Moderate to Severe Crohn's Disease? A Meta-analysis of Controlled Clinical
      Trials.
AB  - BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) antibodies are currently used
      in patients with moderate to severe Crohn's disease (CD) who are unresponsive to
      conventional therapies. Certolizumab pegol (Cp) is one of the anti-TNF-alpha
      agents introduced for the management of CD and rheumatoid arthritis. OBJECTIVES:
      The aim of this meta-analysis is to assess the efficacy of Cp in inducing
      clinical response and remission in CD and the associated adverse events. The
      effect of Cp in terms of CD patients' C-reactive protein (CRP) level was also
      studied. PATIENTS AND METHODS: Literature was searched for studies investigated
      the efficacy of Cp on inducing clinical response and maintaining remission in the
      patients with CD between 1966 and July 2012. RESULTS: Among 165 potentially
      relevant studies, six with a total of 1695 patients met the inclusion criteria
      and were meta-analyzed. In comparison to control groups, patients who received Cp
      had a relative risk (RR) of 1.38 with absolute risk reduction (ARR) = 0.12; 95%
      CI = 0.03 to 0.21), number needed for treatment (NNT) = 9; P < 0.0001 ) for
      clinical response and RR of 1.54 (ARR = 0.09; 95% CI = -0.0198 to 0.2), (NNT =
      12; P < 0.0001) for maintenance of clinical remission and non-significant RR of
      1.24 (P = 0.052) for induction of clinical remission. Baseline CRP did not
      significantly alter the magnitude or response. Adverse events were not
      significantly different among patients receiving Cp comparing to placebo.
      CONCLUSIONS: Cp is effective for inducing clinical response and maintenance of
      clinical remission in patients with moderate to severe CD with similar side
      effect profile as the control arms.

PMID- 24578834
TI  - Relationship between Breast Feeding and Obesity in Children with Low Birth
      Weight.
AB  - BACKGROUND: Breast feeding appears to play a role in determining obesity and
      abdominal obesity during childhood, specifically in children with a history of
      low birth weight. OBJECTIVE: The purpose of this study is to investigate the
      relation of breast-feeding with either of abdominal obesity and obesity among
      Iranian school children. MATERIALS AND METHODS: A total of 1184 students (625
      girls and 559 boys), aged 10 to 13 years old, were selected from 112 governmental
      elementary schools in Iran. Height, weight, waist circumference and blood
      pressure were measured using standard instruments and a pretested standardized
      questionnaire was performed for compiling information about family economics and
      educational level, first-degree family history of obesity, history of breast
      feeding, food pattern and birth weight, as well. RESULTS: 13.68% (n = 160) of
      students had a history of low birth weight, and 26.41% of them had abdominal
      obesity. Of all participants, 22.04% were overweight and 5.32% were obese which
      was more prevalent in girls than in boys (P = 0.03). First-degree family history
      of obesity (P = 0.001), excessive gestational weight gain (P = 0.001) and birth
      weight (P = 0.01) were significantly correlated with the prevalence of obesity
      and abdominal obesity during childhood. Moreover the prevalence of abdominal
      obesity in children with low birth weight was significantly correlated with
      breast feeding (P = 0.04); But this relation was not significantly about obesity
      in our participants (P = 0.9). Furthermore duration of breast feeding was
      significantly and inversely correlated with obesity and abdominal obesity in
      schoolchildren with low birth weight (P = 0.01). CONCLUSIONS: The results suggest
      that Breast feeding and its long-term consequences were important factors for
      preventing metabolic syndrome criteria in childhood and later years of life span.
      With regard to the increasing prevalence of obesity in children, more research is
      urgently needed to clarify whether breast feeding have negative consequences for
      the risk of chronic disease in children, especially in children with low birth
      weight.

PMID- 24578835
TI  - Women's Preferences of Method of Delivery and Influencing Factors.
AB  - BACKGROUND: Currently, the rate of caesarean section has been substantially
      increased in developing and developed countries. To determine the factors causing
      such an increase, it is important to determine reasons for women to refuse
      vaginal delivery and preferring caesarean section. OBJECTIVES: To determine
      Turkish women's attitudes and basal knowledge regarding vaginal delivery and
      caesarean section, as well as factors causing women to prefer caesarean section
      even when a medical indication does not exist. PATIENTS AND METHODS: This
      descriptive study consisted of 840 women, completing the questionnaire developed
      by the researchers. RESULTS: Mean age rate of participants was 39.8 +/- 11.8
      years. The most significant reasons of vaginal delivery preferred by participants
      (n = 685) were determined to be healthy and swift recovery period after delivery,
      whereas those preferred by participants (n=155) for caesarean section were being
      safer for babies, easier than vaginal delivery and a less painful method. Higher
      educational status, pregnancy after infertility treatment and undergoing
      caesarean section for the last delivery were determined to be among important
      factors affecting to choose caesarean section. CONCLUSIONS: Information gained
      misleadingly and fears related to vaginal delivery were seen as factors affecting
      women's preferences for delivery. Thus, midwives are required to train both
      pregnant women during antenatal care and all women in society about methods of
      delivery and to give effective counseling.

PMID- 24578836
TI  - Cutaneous malignant melanoma in central iran: a 20-year study.
AB  - BACKGROUND: Skin cancers are the most common cancers around the world. Cutaneous
      malignant melanoma (CMM) is the malignancy of melanocytes that are mainly located
      in the skin and mucous membranes. OBJECTIVE: This study tried to evaluate the
      incidence and mean survival time of cutaneous malignant melanoma (CMM) in Yazd,
      Iran. It seems that the epidemiology and clinical aspects of CMM in Iran are
      different from those in other parts of the world; also due to the limited and
      scattered studies there isn't lot in the literature regarding CMM in Iran.
      MATERIALS AND METHODS: This study used data obtained from the cancer registry
      center in the province of Yazd for a period of 21 years (1988 - 2008). Population
      and statistical data were gathered from "National Organization for Civil
      Registration". Population-based data were analyzed, focusing on the incidence and
      mean survival time over this 21 year period. RESULTS: The mean incidence rate for
      CMM in Yazd-Iran between 1988 and 2008 was 0.40 per 100,000 for males and 0.27
      per 100,000 for females per year, and the incidence of CMM was relatively
      constant during this period of time. The mean survival rates for women were
      better than men (80.5% and 76.3% respectively). CONCLUSIONS: CMM in Yazd is a low
      incidence skin tumor that shows a relatively fixed incidence between 1988 and
      2008, Higher incidences of CMM were found in sun-exposed areas (especially head
      and neck areas), with more incidence in men. Skin cancers and CMM incidence in
      Iran is lower than western countries, most probably due to geographical zone,
      genetic factors, skin type, society-related customs including clothing styles.

PMID- 24578837
TI  - Premenstrual disorders: prevalence and associated factors in a sample of Iranian
      adolescents.
AB  - BACKGROUND: Premenstrual disorders usually refer to Premenstrual Syndrome (PMS)
      and Premenstrual Dysphoric Disorder (PMDD). This study was designed to find out
      the frequency of premenstrual disorders and evaluate the associated factors in a
      sample of Iranian adolescents. OBJECTIVES: This study was conducted to
      investigate the frequency of premenstrual disorders (PMS and PMDD) based on
      Premenstrual Assessment Scale (PAS) and also to determine the association of some
      demographic and menstrual characteristics with these disorders in adolescent
      girls. PATIENTS AND METHODS: This was a cross sectional study. A sample of
      adolescent school girls aged between 14 and 19 years were included in the study.
      Diagnostic assessments were based on Premenstrual Assessment Scale (PAS). The
      data were analyzed in a descriptive fashion and were compared among subgroups of
      the study sample. In addition, demographic and menstrual factors associations
      with premenstrual disorders were assessed. RESULTS: In all 1379 female students
      were included in the study. About 99.5 % of the students reported at least one
      premenstrual symptom. Of these, 66.3% was mild, 31.4% moderate and 2.3% severe. A
      total of 814 girls (59%) met the diagnostic criteria for premenstrual dysphoric
      disorder (PMDD). Most frequently reported symptoms were back pain, lethargy,
      fatigue and anxiety. Early menarche, lower education was associated with higher
      scores on PAS. CONCLUSION: Premenstrual disorders are common in adolescent girls.
      Preventive and treatment strategies are highly recommended.

PMID- 24578838
TI  - Serologic Detection of Anti Toxoplasma gondii Infection in Diabetic Patients.
AB  - BACKGROUND: Toxoplasmosis is caused by the Toxoplasma gondii parasite. The
      parasite is intracellular and can result in severe complications leading to death
      in immuno-deficient patients in particular. Diabetes is an important factor that
      increases susceptibility and risk of various infections in the host. OBJECTIVES:
      The present study focused on the serologic detection of Toxoplasma gondii
      infection in diabetic patients. MATERIALS AND METHODS: Through a case-control
      study, overall 184 serum samples including 91 from diabetic cases and 93 from
      healthy non-diabetic controls were investigated. Cases and controls were matched
      for age and gender. Serum samples were tested for sugar by an enzymatic method,
      and IgG antibodies were tested against Toxoplasma gondii by ELISA method.
      RESULTS: The prevalence of IgG antibodies against Toxoplasma gondii in diabetic
      patients and healthy controls were 60.43% and 38% respectively. Risk of
      toxoplasmosis infection in diabetic patients with was two folds higher than
      healthy controls (RR = 2.21, 95% CI; 1.6 - 3.7, P = 0.001). CONCLUSIONS: Diabetes
      may be caused by Toxoplasma gondii. Presence of T. gondii in the pancreas at the
      same time could directly undermines the pancreas cells. When beta cells are
      destroyed, insulin secretion would then be affected. Probably the destruction of
      T. gondii affects nervous system and damages pancreatic cells leading to
      increased risk of diabetes.

PMID- 24578839
TI  - Antimicrobial susceptibility of clostridium difficile clinical isolates in iran.
AB  - BACKGROUND: Clostridium difficile infection (CDI) is major growing problem in
      hospitals and its high incidence has been reported in recent years. OBJECTIVES:
      The aim of this study was to investigate the antimicrobial susceptibility
      patterns of C. difficile clinical isolates against antibiotics commonly used for
      treatment CDI in hospitalized patients. MATERIAL AND METHODS: During a 12 month
      study, 75 C. difficile isolates were collected from 390 patients with CDI. All
      samples were treated with alcohol and yeast extract broth. The treated
      suspensions were cultured on a selective cycloserine cefoxitin fructose agar
      (CCFA) supplemented with 5% sheep blood and incubated in anaerobic conditions, at
      37  degrees C for 5 days. Cdd-3, tcdA and tcdB genes were identified using PCR
      assay. RESULTS: The prevalence of A(+)B(+) , A(+) B(-) and A(-) B(+) strains were
      64(85.3%), 5(6.7%) and 6(8%) respectively. In vitro susceptibility of 75 clinical
      isolates of C. difficile to 5 antimicrobial agents, including metronidazole,
      vancomycin, clindamycin, erythromycin and cefotaxime were investigated by
      Clinical and Laboratory Standards Institute (CLSI) agar dilution method.
      Metronidazole and vancomycin had good activity against C. difficile isolates with
      MIC90s of 2 and 1 ug/ml, respectively. Seventy one (94.6%) of strains was
      inhibited by concentrations that did not exceed 2ug/ml for metronidazole.
      Resistant to metronidazole observed in 5.3% of isolates. Forty three (57.3%) of
      the isolates were resistant to erythromycin. Of 43 resistant strains to
      erythromycin, 9 (12%) isolates had high-level MIC of more than 64 ug/ml. All
      strains were resistant to cefotaxime. Sixty seven (89.3%) isolates were resistant
      to clindamycin (MIC90s > 256 ug/ml) and only 6.7% were sensitive to clindamycin.
      Multidrug-resistant (three or more antibiotics) was seen in 36(48%) isolates.
      CONCLUSIONS: Metronidazole and vancomycin still seem to be most effective drugs
      for treatment CDI.

PMID- 24578840
TI  - Developing a Treatment Planning Software Based on TG-43U1 Formalism for Cs-137
      LDR Brachytherapy.
AB  - BACKGROUND: The old Treatment Planning Systems (TPSs) used for intracavitary
      brachytherapy with Cs-137 Selectron source utilize traditional dose calculation
      methods, considering each source as a point source. Using such methods introduces
      significant errors in dose estimation. As of 1995, TG-43 is used as the main dose
      calculation formalism in treatment TPSs. OBJECTIVES: The purpose of this study is
      to design and establish a treatment planning software for Cs-137 Solectron
      brachytherapy source, based on TG-43U1 formalism by applying the effects of the
      applicator and dummy spacers. MATERIALS AND METHODS: Two softwares used for
      treatment planning of Cs-137 sources in Iran (STPS and PLATO), are based on old
      formalisms. The purpose of this work is to establish and develop a TPS for
      Selectron source based on TG-43 formalism. In this planning system, the dosimetry
      parameters of each pellet in different places inside applicators were obtained by
      MCNP4c code. Then the dose distribution around every combination of active and
      inactive pellets was obtained by summing the doses. The accuracy of this
      algorithm was checked by comparing its results for special combination of active
      and inactive pellets with MC simulations. Finally, the uncertainty of old dose
      calculation formalism was investigated by comparing the results of STPS and PLATO
      softwares with those obtained by the new algorithm. RESULTS: For a typical
      arrangement of 10 active pellets in the applicator, the percentage difference
      between doses obtained by the new algorithm at 1cm distance from the tip of the
      applicator and those obtained by old formalisms is about 30%, while the
      difference between the results of MCNP and the new algorithm is less than 5%.
      CONCLUSIONS: According to the results, the old dosimetry formalisms, overestimate
      the dose especially towards the applicator's tip. While the TG-43U1 based
      software perform the calculations more accurately.

PMID- 24578841
TI  - Study on antiphospholipid/anticardioliplin antibodies in women with recurrent
      abortion.
AB  - BACKGROUND: Antiphospholipid antibodies are associated with recurrent abortion
      but correlation between level of antibodies and gestational age of abortion and
      duration post abortion is not clear. OBJECTIVES: Aim of this study was study on
      relation between antiphospholipid antibodies in women with recurrent abortion and
      their gestational age and duration post abortion. PATIENTS AND METHODS: We
      performed a case-control study on 197 pregnant women who had history of
      spontaneous recurrent abortion as case group and 50 pregnant healthy women as
      control group. Demographic characteristic of all participants filled in
      questionnaire forms. Antipospholipid and anticardiolipin antibodies were measured
      in their serum by Enzyme linked Immunoassay with orgenec kits. Data analyzed by
      SPSS software (version 13) and T statistical test. P value less than 0.05 was
      considered significant. RESULTS: Mean age of participants was 24-39 years old.
      The average rate of antiphospolipid antibodies in patients with normal
      anticardiolipin was greater than those with abnormal anticardiolipin and T-test
      showed significant difference between two groups.(P = 0.000) In case group the
      number of abortions was more, mean of antiphosopolipid antibody levels were also
      higher. Mean anticardiolipin and antiphospholipid antibodies rate was greater
      with increasing gestational age at time of first abortion. Almost mean
      antipospholipid and anticardiolipin antibodies in all patients remained in high
      level just in first 5 years with any number of abortions and five years later,
      antibodies began to fall. CONCLUSIONS: Antipospholipid antibodies based on number
      of abortions and gestational age of abortions were increased. Mean
      antipospholipid and anticardiolipin antibodies in all patients remained in high
      level just in first 5 years post abortion and then began to fall.

PMID- 24578842
TI  - Health Related Quality of Life in Iranian Patients With Irritable Bowel Syndrome:
      Reliability and Validity of the Persian Version of the IBS-QOL.
AB  - BACKGROUND: Irritable bowel syndrome (IBS) is a gastrointestinal disease that is
      accompanied by pain, diarrhea, constipation and abdominal bloating. Hence, IBS
      has a major effect on patients' quality of life. OBJECTIVES: The present study
      aimed to examine validity and reliability of the Persian version of the IBS-QOL
      questionnaire in Iran. PATIENTS AND METHODS: The original 34 items of the IBS-QOL
      were translated from English into Persian through a structured procedure for the
      translation and cultural adaptation of the original English IBS-QOL into Persian.
      Ninety one patients who had GI symptoms but did not have any organic diseases
      (including 70 IBS patients diagnosed by Rome II criteria) were recruited from
      teaching hospitals Shiraz University in Iran and completed a Persian version of
      the IBS-QOL along with a Persian version of Room IotaIota and IBS severity index
      (IBSSI). RESULTS: Our findings showed that the IBS-QOL has excellent convergent
      and acceptable discriminant validity. All domains had Cronbach's alpha greater
      than 0.7 except health worry. Seventy patients who were diagnosed as IBS by the
      Room IotaIota had significantly lower scores in the IBS-QOL than those who were
      not (FBD) (43.7 +/- 20.1 vs. 73.4 +/- 14.9, P < 0.01). Age, sex, education or
      marital status did not affect scores in measuring the quality of life.
      CONCLUSIONS: In conclusion, the Persian version of the IBS-QOL provided a well
      defined measure of QOL in IBS patients with high validity and reliability that is
      an appropriate measure to use in further IBS clinical studies in Iran.

PMID- 24578843
TI  - Frequency of rotavirus and adenovirus gastroenteritis among children in shiraz,
      iran.
AB  - BACKGROUND: Viral pathogens are the main cause of acute gastroenteritis in
      developed and developing countries. Rotavirus and adenovirus are the two
      important agents associated with hospitalization for diarrhea especially in
      children. Limitation and control of diarrhea as a costly disease must be
      considered in national health programs. OBJECTIVES: Epidemiological studies on
      viral diarrhea and collecting data for rotavirus and adenovirus prevalence, as
      two important viral agents of gastroenteritis, are valuable for planning of a
      prospective program. MATERIALS AND METHODS: 827 stool samples of pediatrics
      patients with gastroenteritis who were admitted to Dastgheib Hospital, Shiraz,
      Iran, from September 2008 to February 2010 were tested for presence of rotavirus
      and adenovirus using the EIA method. A demographic and clinical study was
      performed to determine the relationship between viral infection and clinical
      outcomes of patients. RESULTS: Rotavirus was identified in 347 patients out of
      827 (42%), adenovirus was detected in 76 (9%) of samples and 34 (4%) of patients
      had rotavirus-adenovirus co-infection. Diarrhea was the most common symptom in
      viral infected patients. CONCLUSIONS: Given the non-specific symptoms of these
      viruses and the high prevalence of viral diarrhea in our region, more
      laboratories should be equipped for virus detection and vaccination might be
      considered as a prevention strategy.

PMID- 24578844
TI  - The Effects of Lavandula Angustifolia Mill Infusion on Depression in Patients
      Using Citalopram: A comparison Study.
AB  - BACKGROUND: Many herbs have been used to treat psychiatric disorders including
      anxiety and depression in traditional medicine. OBJECTIVES: This study was
      carried out to determine the effect of using Lavandula angustifilia infusion on
      depression in patients taking Citalopram. PATIENTS AND METHODS: Among all
      patients referred to the Hajar Hospital psychiatric clinic, Shahrekord, Iran, 80
      patients who met the criteria of major depression according to the structured
      interviews and the Hamilton questionnaire for Depression were included in the
      study. They were randomly assigned into two groups of experimental treatment
      group and standard treatment group at this study. In standard treatment group,
      the patients were given Citalopram 20 mg. In experimental treatment group, the
      patients took 2 cups of the infusion of 5 g dried Lavandula angustifilia in
      addition to tablet Citalopram 20 mg twice a day. The patients were followed up
      for four and eight weeks of the study onset using Hamilton Scale questionnaire
      and treatment side effects form. Data were analyzed using student t-test, pair t
      test and chi square. RESULTS: After four weeks of the trial onset, the mean
      depression score according to the Hamilton Scale for Depression was 17.5 +/- 3.5
      in the standard treatment group and 15.2 +/- 3.6 in the experimental treatment
      group (P < 0.05). After eight weeks, it was 16.8+/-4.6 and 14.8+/-4 respectively
      (P < 0.01). In addition, the most commonly observed adverse effects were nausea
      (12.8 %) and confusion (10%). In terms of side effects, there were no significant
      differences between two groups. CONCLUSIONS: Considering the results of this
      study, Lavandula angustifilia infusion has some positive therapeutic effects on
      depressed patients most importantly decreases mean depression score and might be
      used alone or as an adjunct to other anti-depressant drugs.

PMID- 24578845
TI  - Invasive Pneumococcal Disease (IPD) Serotype Frequency in Iranian Patients.
AB  - BACKGROUND: Streptococcuspneumoniae as a Gram positive diplococcic is a major
      worldwide causative agent of morbidity and mortality among young children and the
      aged. In addition, Streptococcus pneumoniae is a versatile human pathogen causing
      infectious disease ranging from mild infection (i.e. otitis media) to life
      therating pneumonia and meningitidis in many countries. OBJECTIVES: The aim of
      this study was to determine the frequency type of Streptococcuspneumoniae in
      Invasive pneumococcal disease (IPD) in Iranian patients. PATIENTS AND METHODS: A
      total of 135 Streptococcuspneumoniae strains were isolated from patients
      infectious suspected of invasive streptococcal disease. They were subjected to
      PCR and bacteriological methods. Out of which, 134 strains of S. pneumoniae were
      serotyped and confirmed by PCR method. The data were analyzed by SPSS version
      17.0. RESULTS: The results of this study showed some S. pneumoniae serotypes were
      found in both sexes and some only in one sex invasive infections. For example,
      serotypes 10, 14, 18 and 22 were only in female patients with infections.
      CONCLUSIONS: The analysis of the results had suggested that serotypes 6 from Lung
      and 19 from Eye are the most abundant bacterial strains isolated from patients.
      The diseases could be prevented by using the Pneumococcal vaccine.

PMID- 24578847
TI  - Effectivity of one session charcoal hemoperfusion treatment in severe
      carbamazepine poisoning.
AB  - A carbamazepine intoxication with suicide attempt is a relatively common clinical
      problem that presenting with coma, respiratory depression, arrhythmia,
      hemodynamic instability and even death. We report a case of severe carbamazepine
      poisoning that was successfully treated with one session charcoal hemoperfusion.
      On admission, the patient was comatose and required ventilator support.
      Hemoperfusion with coated activated charcoal successfully decreased the serum
      carbamazepine concentration from 45 ug mL(-1) to 21 ug mL(-1) within 2 h, with
      subsequent clinical improvement. 

PMID- 24578846
TI  - Relationship between ways of coping and quality of life in married women: toward
      mental health promotion.
AB  - BACKGROUND: Adaptive ways of coping with stress are as a major component of
      mental health and also this is considered as a key element in quality of life.
      OBJECTIVES: The aim of this study was to investigate the relationship between
      quality of life and coping mechanisms in married women ages between 18-65 years
      in order to develop appropriate intervention programs to promote mental health.
      PATIENTS AND METHODS: THIS STUDY WAS A PART OF INTERVENTIONAL PROJECT TO MENTAL
      HEALTH PROMOTION IN MARRIED WOMEN THAT COMPLETED THROUGH A CROSS SECTIONAL
      STUDIES USING TWO STANDARD QUESTIONNAIRES: Ways of Coping (WOC) and Quality of
      Life questionnaire (WHO, QOL-BREF). RESULTS: The most and the least used ways in
      coping with stress were Planful Problem Solving and Confronting Coping.
      Considering the quality of life, the most and the least scores were related to
      social dimension and mental health. Also women who have higher quality of life
      used more Positive Reappraisal way and less Escape-Avoidance way to deal with
      stress (P < 0.05). CONCLUSIONS: It seems that implementation of an appropriate
      interventional program related to adaptive ways of coping in order to deal with
      stress is effective in mental health and quality of life promotion.

PMID- 24578848
TI  - Attitude and Usage of Mobile Phone among Students in Yazd University of Medical
      Science.

PMID- 24578849
TI  - Does DNA Methylation Plays a Critical Role in Osteoblastic Differentiation of
      Mesenchymal Stem Cells (MSCs)?

PMID- 24578850
TI  - Twin Pregnancy of a Complete Hydatidform Mole and a Co-existent Fetus: A Very
      Rare Case Report.

PMID- 24578851
TI  - Bacteria isolated from patients with cholelithiasis and their antibacterial
      susceptibility pattern.

PMID- 24578852
TI  - Anomalies of the inferior vena cava and renal veins and implications for renal
      surgery.
AB  - Abnormalities of the inferior vena cava (IVC) and renal veins are extremely rare.
      However, with the increasing use of computed tomography (CT), these anomalies are
      more frequently diagnosed. The majority of venous anomalies are asymptomatic and
      they include left sided IVC, duplicated IVC, absent IVC as well as retro-aortic
      and circumaortic renal veins. The embryological development of the IVC is complex
      and involves the development and regression of three sets of paired veins. During
      renal surgery, undiagnosed venous anomalies may lead to major complications.
      There may be significant hemorrhage or damage to vascular structures. In
      addition, aberrant vessels may be mistaken for lymphadenopathy and may be
      biopsied. In this review we discuss the embryology of the IVC and the possible
      anomalies of IVC and its tributaries paying particular attention to diagnosis and
      implications for renal surgery. 

PMID- 24578853
TI  - Urine markers and prostate cancer.
AB  - Prostate cancer (PCa) is globally the most common cancer in men, with an
      estimated prevalence of more than two million cases. Given the poor success rate
      in treating advanced PCa, intervention in early stages may reduce the progression
      of a small, localized carcinoma to a large metastatic lesion, thereby reducing
      disease-related deaths. Urine is readily available and can be used to detect
      either exfoliated cancer cells or secreted products. The major advantages of
      urine-based assays are their noninvasive character and ability to monitor PCa
      with heterogeneous foci. The aim of this review was to summarize the current
      evidence regarding performance characteristics of tests proposed for urine-based
      prostate cancer detection. 

PMID- 24578854
TI  - Education concerning carcinoma of prostate and its early detection.
AB  - INTRODUCTION AND OBJECTIVES: Prostate cancer is the most common male cancer.
      Insufficient knowledge of PCa among men causes its low detection. Lack of
      essential actions in health education and widely understood prophylaxis, the need
      of the latter are maybe responsible for the increasing mortality rate. According
      to our assumption, educating men increase their awareness on the need of
      screening tests and results in increasing reporting to physical examinations.
      This in turn allows for an early detection of the disease. MATERIAL AND METHODS:
      A research was conducted between the years 2003-2009 on the knowledge of PCa
      among 260 men. They were divided into two groups. Group A - 63 patients treated
      for carcinoma of prostate and group B - 197 men reporting spontaneously to
      screening tests. In order to check the adopted hypothesis, we prepared an
      educational material and test of knowledge - test with a questionnaire. Knowledge
      was evaluated before (test I) and after the education process (test II). Until
      2009, we were monitoring the number of patients from group B reporting to
      screening tests and their knowledge was once again checked (test III). Two
      subgroups C and D were created from group B - 117 healthy men and 80 with
      diagnosed diseases respectively (70 with benign prostatic hyperplasia, 7 with
      prostatitis, and 3 with carcinoma of prostate). Patients with prostatitis and PCa
      and 3 patients from group C not reporting to the tests were excluded from further
      monitoring. Maths statistics with the use of SPSS 12.0 PL program and Statistica
      6.0 constituted the base for working out the results. RESULTS: We observed a
      higher knowledge about carcinoma of prostate in group A than in group B (p
      <0.0001) and it increased after 5 years in group D (p <0.0001) in comparison to
      group C. Patients aged >40 from groups C and D were interested in health care
      (p<0.01) as much as patients aged 40-49, 50-59 and 60-69. In men >70 a lower
      level of motivation was observed. The interest was proportional to the level of
      education, and this was differentiating in an analogical way the motivation to
      extend knowledge about prostate cancer (p<0.001). The place of living was
      determining the level of motivation for broadening knowledge - in bigger towns in
      a greater extent (p <0.01). The frequency of reporting to screening tests during
      a period of 5 years was comparable in groups C and D, regardless of knowledge
      tests' results. Health risk awareness following the education process was
      motivating men to undergo screening tests (p <0.05). This confirms our own
      research hypothesis. Regardless of the age bracket, the obtained result of
      knowledge test II was higher than test I and the result of test III was lower
      than test II, respectively: p <0.01; p <0.08; p <0.01; p <0.001. The level of
      knowledge test III among all examined patients was higher in comparison to test I
      - p <0.01; p <0.001; p <0.001 respectively. White-collar workers obtained in test
      I a result higher than blue-collar workers, unemployed or retired people p <0.001
      and p <0.01 respectively. Unemployed and retired people obtained more scores than
      blue-collar workers (p <0.05). Both in professional workers and retired people
      test III was higher than test I - p <0.001 and p <0.001 respectively. In 7
      examined men prostate cancer was diagnosed; in group B in 3 in an advanced state,
      and during 5 years in group C - in 4 men at an early development stage.
      CONCLUSIONS: In the examined men, we observed an almost complete lack of
      knowledge about carcinoma of prostate, hence they did not report to screening
      tests.The education process influenced the level of knowledge about carcinoma of
      prostate. The examined men >40, inhabitants of bigger towns with higher
      education, less with secondary education and still less with elementary education
      showed interest in improving their health knowledge.Due to increasing knowledge
      about carcinoma of prostate, patients were undertaking systematic tests - on
      average once a year. It confirmed the fact that education on prostate cancer
      influences its early detection.Education on carcinoma of prostate on a large
      scale may lead to decreasing morbidity and mortality rates.

PMID- 24578855
TI  - Independent predictors of biochemical recurrence after radical prostatectomy: a
      single center experience.
AB  - INTRODUCTION: The aim of study was to establish pretreatment and postoperative
      factors which could predict the early biochemical recurrence after radical
      prostatectomy. MATERIALS AND METHOD: 754 patients had undergone radical
      prostatectomy since January 2002 to December 2008 in our department and were
      included in this prospective study. Exclusion criteria were: neoadjuvant or
      adjuvant treatment (radiation or hormonal treatment) and N+. Following parameters
      were evaluated: age, PSA at time of biopsy, time period from biopsy to operation,
      biopsy and postoperative Gleason score, stage, high grade intraepithelial
      neoplasias, perineural invasion. Biochemical recurrence was detected if PSA value
      after radical prostatectomy was >=0.2 ng/ml. All factors likely to be predictive
      were evaluated by univariate analysis (Log-rank test). Multivariate analysis
      using Cox model was completed for all factors with p value <0.1 at univariate
      analysis. RESULTS: Final analysis was done using data of 496 patients. We
      detected 53 (10.7%) biochemical recurrences. Calculated actuarial biochemical
      recurrence free survival reached 64%. Multivariate analysis highlighted that PSA
      >10 ng/ml (HR 2.45, p = 0.008), pathological stage >=pT3 (HR 2.371, p = 0.02),
      postoperative Gleason score >=7 (HR 2.149, p = 0.049), positive surgical margins
      (HR 2.482, p = 0.014) and absence of high grade intraepithelial neoplasia in
      removed prostate (HR 0.358, p = 0.006) are independent factors influencing
      biochemical recurrence after radical prostatectomy. CONCLUSION: Patients with
      higher PSA, locally advanced disease, positive surgical margins, and Gleason
      score >=7 are at the highest risk for biochemical recurrence.

PMID- 24578856
TI  - Comparison of the effectiveness of crushing concrements in the urinary tract with
      the use of holmium laser and sonotrode.
AB  - INTRODUCTION: Holmium lasers and ultrasound probes are widely used in urinary
      stone lithotripsy. The authors present a comparison of both methods in urinary
      stones lithotripsy. MATERIALS AND METHODS: We analyzed 164-patients who underwent
      endoscopic lithotripsy. Ninety-eight of them (group I) were treated with the
      holmium laser Omni-Pulse Max 80 and were compared to the other 66-patients (group
      II) who were operated on with an ultrasound probe (sonotrode). Prior to the
      procedures, all patients were exposed to urological ultrasound and radiological
      imaging in order to localize the stone. The state where the stones were invisible
      in the radiological and renal ultrasound imaging that was performed after the
      operation was considered to be effective. Patients were operated under
      intravenous general or subepidural anesthesia. RESULTS: The effectiveness of
      laser lithotripsy in the bladder amounted to 100% (25 of 25 patients). In the
      case of stones localized in the ureter it reached 89%. The total effectiveness of
      the procedure reached 92% (90 out of 98 procedures). In group II, the total
      effectiveness of the procedure reached 79% (52 out of 66 procedures). In group I,
      two cases the inflammatory changes of the ureter made the endoscopy impossible.
      These two patients were operated with open surgery. In one case, the laser
      lithotripsy was complicated with a perforation of the ureter. CONCLUSION: The
      results prove that laser lithotripsy is a method of high effectiveness with a low
      risk of complication. It might surpass sonotrode and become its alternative. Both
      methods have both advantages and disadvantages.

PMID- 24578857
TI  - Effects of pentoxifylline on renal structure after urethral obstruction in rat: A
      stereological study.
AB  - OBJECTIVE: Chronic renal failure due to tubulointerstitial fibrosis is one of
      complications of lower urinary tract obstruction. Since pentoxifylline is a
      xanthine derivative that inhibits some inflammatory mediators, we conducted this
      study to investigate whether pentoxifylline inhibits renal fibrosis in a rat
      model of partial urethral obstruction (PUO). METHODS: All the rats underwent
      experimental PUO. Then, the animals were divided randomly into two groups:
      positive control group and experimental group. The experimental group received
      pentoxifylline 100 mg/kg per day via oral gavages for 4-weeks. The control group
      received the same dose of normal saline. After 4-weeks, all the rats underwent
      left nephrectomy. Kidney volume and weight and fractional and absolute volumes of
      the glomeruli, tubules, interstitium and vessels were determined with
      stereological methods. To reduce the workload of reference (kidney) volume
      estimation, the total kidney volume was determined after estimation of tissue
      shrinkage on isotropic uniform random histological sections. The total volume
      (amount) of each renal structure including fibrosis was estimated to avoid the
      bias conclusion due to relying on volume density alone. RESULTS: The absolute
      volume of interstitial fibrosis was lower in the experimental group (PUO with
      pentoxifylline treatment) (~84%; p <=0.006) in comparison with the control group
      (PUO with no treatment). CONCLUSION: Pentoxifylline reduces interstitial renal
      fibrosis after partial urethral obstruction in rats.

PMID- 24578858
TI  - Semen quality in men from subfertile couples from the region of Lodz (Poland)
      according to the new reference values recommended by WHO 2010.
AB  - The semen analysis is the main diagnostic tool for evaluating the male fertility
      potential. The standard semen analysis includes evaluation of the sperm
      concentration, motility, and their morphology. The most important question is
      whether the results from semen analysis may be accurate markers for male
      fertility. Therefore, we retrospectively studied sperm quality among men
      attending the infertility clinic due to reproductive problems consistent with the
      WHO manual from 1999, which were reassessed according to the manual from 2010.
      Semen results from 571 males from couples undergoing fertility investigation were
      analyzed. All subjects included in the study had no abnormalities during
      examination. In 64 samples (11.2%), a leukocyte count above 1 x 10(6)/ml was
      found and their semen volume (median 3.2 ml) was significantly lower in
      comparison with the group without leukocytes (3.6 ml; p <0.001). Normal semen
      parameters were found in 290 subjects (50.8%) according to the 1999 manual and in
      362 men (63.4%) according to the 2010 manual. The normozoospermia group,
      according to the 2010 manual, had a significantly lower percentage of sperm with
      progressive motility, motile sperm concentration, and total number of motile
      sperm in comparison with the normozoospermia group according to the manual from
      1999. It seems that routine semen analysis is not sufficient to estimate male
      fertility potential and some men with normal semen parameters may be subfertile.
      Further investigations are needed. 

PMID- 24578859
TI  - Laparoscopic radical nephrectomy for large renal tumor - a case report and
      technical considerations.
AB  - In comparison to an open procedure, the laparoscopic radical nephrectomy has
      demonstrated advantages in regard to perioperative morbidity, postoperative pain,
      time of hospitalization, and convalescence. However, most series of laparoscopic
      radical nephrectomy are confined to T1 tumors. The authors present a case of a
      large-volume- T2 renal tumor treated laparoscopically. The aim of the study is to
      present the operative technique and to discuss several unique problems that arise
      during the laparoscopic procedure in patients with large renal masses. 

PMID- 24578860
TI  - Hemoperitoneum secondary to bleeding of a hepatic metastasis of testicular
      carcinoma.
AB  - Testicular cancer is the most common type of cancer among young patients. At the
      moment of diagnosis, between 30% and 50% of them have developed metastases, which
      affect retroperitoneal lymph nodes and lungs especially. Hepatic compromise is
      rare and is associated with poor prognosis. Besides this, hepatic lesions can
      complicate with necrosis and overgrowth, a phenomenon that is mainly seen in
      primary lesions. Furthermore, bleeding of secondary lesions is very uncommon. We
      present a case of a patient with massive hemoperitoneum secondary to rupture of
      hepatic metastatic lesions of a primary testicular tumor. 

PMID- 24578861
TI  - Schwannoma, a rare tumor of the seminal vesicle.
AB  - We present a rare case of a schwannoma of the seminal vesicle that occurred in a
      43-year-old male with symptoms of the lower urinary tract. Ultrasonography and
      magnetic resonance imaging documented a solid mass in the patient's left seminal
      vesicle. A transvesical approach with a transtrigonal midline incision was
      successfully performed. The microscopic aspect was compatible with schwannoma. 

PMID- 24578862
TI  - Conservative treatment of an intraperitoneal bladder perforation.
AB  - INTRODUCTION: The management of bladder rupture depends on its anatomical
      location. MATERIAL AND METHODS: Case report and review of the pertinent English
      language literature. RESULTS: A 56-year-old man with history of an anterior
      rectum resection with partial cystectomy presented with signs of acute renal
      failure, and later with a tender, distended abdomen. Work-up including serum and
      ascites biochemistry, cystoscopy, and CT cystography diagnosed urinary ascites.
      The small intraperitoneal bladder rupture was treated conservatively via
      continued urinary drainage under urinary antibiotic prophylaxis until closure.
      CONCLUSION: A conservative treatment of a small intraperitoneal bladder
      perforation is possible under certain conditions.

PMID- 24578863
TI  - Nephrobronchial fistula. A case report and review of the literature.
AB  - Nephrobronchial fistulas are a rare complication of xanthogranulomatous
      pyelonephritis. We report the diagnosis of such a case together with its
      investigation, management and a review of current literature. 

PMID- 24578864
TI  - Major and trace elements in lithogenesis.
AB  - The process of crystallization in the urinary tract occurs when the equilibrium
      between promoting and inhibiting factors is broken. Many theories have been
      published to explain the mechanism of urinary stones formation; however, none of
      these theories has paid attention to trace elements. Their role in lithogenesis
      is still unclear and under debate. The findings of some studies may support the
      thesis that some major and trace elements may take part in the initiation of
      stone crystallization for instance as a nucleus or nidus for the formation of the
      stone, or simply contaminate the stone structure. This review presents a
      comprehensive account of the basic principles of the basic data and the role of
      major and trace elements in lithogenesis. 

PMID- 24578865
TI  - Complications of cataract surgery in patients with BPH treated with alpha 1A
      blockers.
AB  - The prevalence of benign prostate hyperplasia (BPH) and cataract increases with
      age. Both diseases may develop concomitantly and may affect almost 50% of elderly
      men as comorbidities. Cataract is treated surgically and it has been reported
      that there may be an association between use of alpha-blockers for BPH,
      particularly alpha1A-adrenergic receptor selective drugs, and complications of
      cataract surgery known as Intraoperative Floppy Iris Syndrome (IFIS). The article
      reviews literature published on this topic and provides recommendations on how to
      reduce incidence of iatrogenic IFIS or its severity and outcomes in patients with
      BPH. 

PMID- 24578866
TI  - What is the possible role of PSA doubling time (PSADT) and PSA velocity (PSAV) in
      the decision-making process to initiate salvage radiotherapy following radical
      prostatectomy in patients with prostate cancer?
AB  - This article is an attempt to present a contemporary view on the role of the
      kinetics of PSA levels as defined by PSA doubling time (PSADT) and PSA velocity
      (PSAV) in the decision-making process to initiate salvage radiotherapy in
      patients with prostate cancer after radical prostatectomy (RP). The dynamics of
      the rise of PSA levels may be an early endpoint parameter, preceding the
      diagnosis of distant metastasis or death due to prostate cancer based on a single
      PSA determination. Thus, it seems reasonable to include the kinetics of PSA
      levels, apart from single PSA determination, in the decision-making algorithm. In
      a group of patients after RP, PSADT might be an early endpoint that could replace
      cause-specific survival rate as a late endpoint. PSADT allows distinguishing
      subgroups of patients at high risk of distant metastases and death, which in turn
      may lead to a change in the further treatment strategy. Therefore, patients with
      short PSA doubling time should become a subgroup, in which hormonal therapy
      should be considered. To date, there is no unanimous consent to accept the
      criteria of assessment of the dynamics of PSA levels as determinants of treatment
      in case of recurrences following RP. However, a number of non-randomized clinical
      trials in patients after RP suggest it would be useful to include these
      parameters in the decision-making process. For instance, a relationship was found
      between increased PSA velocity (>2 ng/mL/year) before initiation of oncological
      treatment and increased (12-fold) risk of death. A number of well-documented
      retrospective analyses show that PSADT is one of the most important parameters to
      describe the disease aggressiveness. It has to be stressed that single
      determination of PSA levels is much less precise in terms of describing the
      biological aggressiveness of prostate cancer than PSADT. Of course, the question
      regarding the need to include the PSA levels kinetic parameters as crucial
      elements of patient management algorithms can be answered in a definitive manner
      only by randomized clinical trials. 

PMID- 24578867
TI  - Radical and sparing surgical treatment of patients with upper urinary tract
      transitional cell carcinomas (UUT -TCC) - preliminary results.
AB  - INTRODUCTION: Tumors originating from transitional epithelium of the renal pelvis
      and ureter are infrequent. Their course is asymptomatic at early stages of the
      disease, and diagnosis and institution of appropriate treatment delayed. The aim
      of the study is to assess the results of treatment in patients with upper urinary
      tract transitional cell carcinomas (UUT-TCC). MATERIAL AND METHODS: Fifteen
      patients treated in 2005-2010 for UUT-TCC were qualified for the retrospective
      study. Clinical symptoms, diagnostic methods, tumor location, clinical stage and
      histopathological characteristics of the tumors were assessed. Then, the
      instituted treatment and its results were analyzed. RESULTS: The average follow
      up period was 51 month (range 6-65), UUT-TCC accounted for 6.7% of renal tumors
      treated. Concurrent treated vesical tumors were observed in 4 (26.7%) patients.
      Primary UUT-TCC was diagnosed in 10 (66.7%) patients. Radical surgery was
      performed in 10 (66.7%) patients, whereas 5 (33.3%) underwent sparing operations.
      Macroscopic hematuria was the predominant clinical symptom. In most cases T2-T3
      clinical stage (60.0%) and high-grade (66.7%) were observed. Development of an
      upper urinary tract tumor after treatment of a vesical tumor was noted in 4
      (26.7%) patients. During the follow-up period, urinary bladder carcinomas were
      diagnosed in 5 (33.3%) patients with primary upper urinary tract tumors.
      CONCLUSIONS: Nephroureterectomy remains the standard treatment for UUT-TCC. Organ
      sparing surgery is possible in selected patients with low clinical stage and low
      grade tumors. Patients treated for urinary bladder carcinomas require regular
      monitoring of the upper urinary tract.

PMID- 24578868
TI  - Importance of prostate volume and urinary flow rate in prediction of bladder
      outlet obstruction in men with symptomatic benign prostatic hyperplasia.
AB  - OBJECTIVES: To predict bladder outlet obstruction with parameters of non-invasive
      investigations for patients with symptomatic benign prostatic hyperplasia.
      PATIENTS AND METHODS: A sample of 122 men with moderate to severe lower urinary
      tract symptoms suggestive of benign prostatic hyperplasia was selected.
      Transrectal prostate ultrasound, free flow measurement, and transabdominal
      ultrasound for residual urine were carried out together with digital rectal
      examination for all patients. All patients underwent urodynamic pressure/flow
      test. Two groups of obstructed (91 patient) and equivocal/unobstructed (31
      patient) were analyzed. Probabilistic model based on logistic regression was
      developed for prediction of obstruction. RESULTS: Various parameters were
      compared in obstructed and non-obstructed/equivocal groups, highlighting
      important parameters for obstruction. Correlation analysis indicates higher
      obstruction dependence on average and peak flow rates and lower dependence on
      total prostate and transition zone volumes, transition zone index. Binary
      logistic regression model suggests that average flow rate combined with total
      prostate volume is the best predictor of obstruction (83% of correct predictions;
      PPV = 92%; NPV = 52%) in the analyzed sample. The analyzed model suggests that
      peak flow rate could also be almost equally important parameter instead of
      average flow rate. CONCLUSIONS: The study suggests that average/peak flow rate
      combined with total prostate volume can be used for prediction of obstruction.
      The developed probabilistic model helps to determine patients who need invasive
      urodynamic testing for decision on surgical treatment.

PMID- 24578869
TI  - Our experience in the treatment of priapism.
AB  - Priapism is a persistent erection without sexual stimulation that cannot be
      relieved by orgasm. Its etiology includes the impaired mechanism of detumescence
      caused by the abundant release of neurotransmitters, venules obstruction,
      impairment of the intrinsic mechanism of detumescence, or prolonged relaxation of
      the intracavernous smooth muscles. Treatment of priapism is conservative,
      pharmacological, or surgical. Efficient treatment options include the
      intracavernous vasoconstrictor injections or surgical shunting. Alternative
      treatment options include the intracavernous methylene blue injections or
      selective penile arterial embolization. Between 2001 and 2009, we treated 10
      patients with priapism at our clinic. According to our data, priapism as a
      complication after intracavernous administration of prostaglandin E1 occurs in
      2.7% of patients, after additional administration of prostaglandin E1 and
      phentolamine - in 5.0% patients, after administration of papaverine - in 8.3%
      patients. The obtained results allow recommendation of prostaglandin E1 as a
      medication of choice among the vasoactive substances for intracavernous use due
      to high efficacy and low side effects. Initially all cases of priapism must be
      treated pharmaceutically, but can be converted to surgery as needed. Unilateral
      transcaputal puncture of the cavernous body (shunting after Winter) in our
      patients with ischemic priapism allowed to achieve detumescence in 100% of cases
      without subsequent recurrence and to restore erectile function in 30% of
      patients. 

PMID- 24578870
TI  - Long-term results after endoscopic VUR-treatment using dextranomer / hyaluronic
      acid copolymer - 5-year experience in a single-center.
AB  - BACKGROUND: A number of bulking agents have been used for the endoscopic
      correction of vesicoureteral reflux in children. We present our long-term results
      of endoscopic use of dextranomer/hyaluronic acid copolymer (Deflux((r))) for VUR
      treatment in children. PATIENTS AND METHODS: Between 2004 and 2008, 21 children
      underwent endoscopic subureteral injection of Deflux((r)) in 30 ureters as an
      outpatient procedure. Twelve children had unilateral reflux (2 duplicated
      systems) and nine had bilateral reflux. Median age was 5-years (6-months to 14.9
      years). Six weeks postoperatively, a voiding cystourethrogram was performed. This
      study examined the disappearance of VUR and urinary tract infection (UTI) in the
      long-term follow-up as well as QoL (questionnaire of the parents). RESULTS: No
      intra- or postoperative complications had been noticed. In 25 ureters (83%), VCUG
      showed no VUR 6-weeks postoperatively. Three children received a 2nd injection
      (two successful). After a median follow-up of 2.5 years, 27 ureters in 17
      children (90%) had no urinary tract infection and VUR. The questionnaire results
      in regard to quality of life (QoL) were very good in the successfully treated
      children and the parents would choose the same treatment option again.
      CONCLUSION: Subureteral injection of Deflux((r)) for children with VUR is an
      effective treatment option with a low complication rate.

PMID- 24578871
TI  - Schwann cells - a new hope in tissue engineered urinary bladder innervation. A
      method of cell isolation.
AB  - INTRODUCTION: There are not any effective method to induce the innervation of
      urinary bladder wall graft after augmentation. Neurons from urinary bladder wall
      and omentium can not elongate and branch in graft because of lack of neurotrophic
      factors. The best source of these neurotrophic factors are Schwann cells which
      can be transplanted into urinary bladder wall graft. To transplant Schwann cells
      the proper amount of cells is needed which can be only obtain during in vitro
      Schwann cell cultivation. We introduce the results of Schwann cell isolation and
      in vitro cultivation. MATERIALS AND METHODS: 33 Wistar rats, males (350 gr.) were
      used in this study. Animal were divited into two groups (n = 15). Cell cultures
      were established in both groups on 5, 6, 7, 8 nad 9 day after nerve injury. In
      first group the digestion time with colagenase and trypsyne was 2.5 h and in
      second one 3.5 h. RESULTS: A larger number of cells were isolated from the
      degenerated sciatic nerve. Colonies of cells that morphologically resembled
      Schwann cells were visible by light microscopy on the second day of in vitro
      cultivation. Homogeneity of the primary cultures increased in the last day of
      cultivation to 60%. CONCLUSIONS: Schwann cells isolation from predegenerated
      peripheral nerve is effective and can delivered require amount of cells for
      transplantation to urinary bladder graft.

PMID- 24578872
TI  - A physical sign of coital rupture of superficial dorsal vein of penis.
AB  - A 39-year-old man presented with penile swelling, pain and hematoma associated
      with sexual intercourse. On exploration, he was found to have ruptured the
      superficial dorsal vein of penis, which was ligated. He had an uneventful
      postoperative recovery and has resumed normal sexual life. A rectangular-shaped
      suprapubic and distal penile hematoma with sparing of the proximal penile skin
      was observed. We believe that this physical sign could aid clinical diagnosis of
      a ruptured superficial dorsal vein of penis. 

PMID- 24578873
TI  - An unusual foreign body in urethra: nail clippers.
AB  - A 37-year-old mentally retarded male patient complained of voiding difficulties.
      Physical examination revealed a foreign body in the urethra. The foreign body was
      found to be nail clippers and was removed with open surgery. This case of self
      inserted nail clippers in the urethra by the patient is the first published
      report to our knowledge. 

PMID- 24578874
TI  - Acute urinary retention in a patient with extended cystitis glandularis.
AB  - Cystitis glandularis (CG) is defined as glandular metaplasia of bladder
      urothelium. In most cases the course of CG is asymptomatic. However, some
      patients complain of hematuria and lower urinary tract symptoms (LUTS) of varying
      degrees. We present a case of 45-year-old man with an extensive CG causing acute
      urinary retention. Although it was initially treated as an infection, prompt
      ultrasound and cystoscopy helped to establish the diagnosis. Transurethral
      resection of the cyst with biopsy of the bladder mucosa was then performed.
      Immediately after surgery the patient noticed significant improvement in urine
      passing. During the 2-month follow-up there was no relapse. 

PMID- 24578875
TI  - Eight-year survival and continuation of therapy in a patient suffering from
      prostate cancer with metastases and pathological fractures of vertebrae.
AB  - Prostate cancer (PCa) is a major health problem and one of the main causes of
      cancer mortality in men [1]. In patients with PCa, bone metastases manifest in
      100% of patients when the PSA level exceeds 100 ng/ml causing pains and posing a
      risk for pathological fractures [2]. We report a case of a 70-year-old male with
      PCa and pathological fractures of the vertebrae, in whom we observed long-term
      regression and an 8-year-survival while undergoing continuous therapy. As far as
      we know, this is the first reported case in literature with such an unexpected
      outcome. 

PMID- 24578876
TI  - A technique for catheter placement after transurethral resection of the prostate
      complicated with undermining of the trigone of the bladder.
AB  - Authors presented 17 patients in whom two techniques for catheterization of the
      bladder after transurethral resection of the prostate complicated with
      undermining of the trigone of the bladder were applied. The first maneuver, used
      in twelve patients, was the insertion of a rigid stylet made from a 10F pneumatic
      probe used for percutaneous nephrolithotripsy into the Foley catheter in order to
      insert the catheter into the bladder in cystoscope manner. In the remaining five
      patients, the second maneuver was the insertion of a Dufour catheter over the
      guide wire left in bladder through the resectoscope sheath. These techniques
      seemed to be easy and safe. 

PMID- 24578877
TI  - The integral system.
AB  - The Integral System is a total care management system based on the Integral
      Theory which states 'prolapse and symptoms of urinary stress, urge, abnormal
      bowel & bladder emptying, and some forms of pelvic pain, mainly arise, for
      different reasons, from laxity in the vagina or its supporting ligaments, a
      result of altered connective tissue'. NORMAL FUNCTION: The organs are suspended
      by ligaments against which muscles contract to open or close the their outlet
      tubes, urethra and anus. These ligaments fall naturally into a three-zone zone
      classification, anterior, middle, and posterior. DYSFUNCTION: Damaged ligaments
      weaken the force of muscle contraction, causing prolapse and abnormal bladder and
      bowel symptoms. DIAGNOSIS: A pictorial diagnostic algorithm relates specific
      symptoms to damaged ligaments in each zone. TREATMENT: In mild cases, new pelvic
      floor muscle exercises based on a squatting principle strengthen the natural
      closure muscles and their ligamentous insertions, thereby improving the symptoms
      predicted by the Theory. With more severe cases, polypropylene tapes applied
      through "keyhole" incision using special instruments reinforce the damaged
      ligaments, restoring structure and function. Problems that can be potentially
      addressed by application of the Integral SystemUrinary stress incontinenceUrinary
      urge incontinenceAbnormal bladder emptyingFacal incontinence and "obstructed
      evacuation" ("constipation")Pelvic pain, and some types of vulvodynia and
      interstitial cystitisOrgan prolapse. CONCLUSIONS: Organ prolapse and symptoms are
      related, and both are mainly caused by laxity in the four main suspensory
      ligaments and perineal body. Restoration of ligament/fascial length and tension
      is required to restore anatomy and function.

PMID- 24578878
TI  - Treatment of mixed urinary incontinence.
AB  - INTRODUCTION: Mixed urinary incontinence (MUI) is a prevalent condition and
      imposes a significant impact on a woman's quality of life. Treatment is often
      challenging, as a single modality may be inadequate for alleviating both the urge
      and stress component. MATERIALS AND METHODS: A MEDLINE search was conducted
      regarding English-language literature pertaining to the pathophysiology,
      diagnosis of, and treatment for MUI. Non-English language articles were
      considered if they could be translated into English using GOOGLE translator.
      RESULTS: The identification of an ideal single treatment has also been made more
      challenging by the poor characterization of the pathophysiology of MUI.
      Behavioral and lifestyle modification, as well as pelvic floor muscle therapy,
      should be considered first-line options for all women with MUI. Treatment of the
      urge component with anti-muscarinics is effective; however the stress component
      is likely to persist after therapy. Anti-incontinence surgery may have a positive
      impact on both the stress and urge components of MUI, with emerging evidence
      suggesting that transobturator MUS may be associated with lower rates of de novo
      and persistent urge component compared to other procedures. The presence of
      concomitant, preoperative detrusor overactivity has not been consistently
      associated with postoperative outcomes. CONCLUSIONS: The optimum treatment of MUI
      may often require multiple treatment modalities. While surgery may have a
      positive impact on both the urge and stress component, its implementation should
      be approached with caution and patients should be carefully selected. Detailed
      informed consent in women with MUI cannot be overstated.

PMID- 24578880
TI  - New valve-mechanical model of urinary tract function: the theory of biological
      dual valves.
AB  - INTRODUCTION: Until now, peristalsis has been the only known method of urine
      transport. The main objective of this paper was to study urinary tract function -
      especially the upper urinary tract, the ureter - from a new mechanical point of
      view. The physical (physical dual valves) and biological basis (biological dual
      valves) of a new functional model is presented based on previous observations and
      knowledge. METHODS: A review of the literature was performed, with special
      emphasis on ureter motility. RESULTS: After analyzing the anatomy and physiology
      of the urinary tract, complemented by basic physical observations, the authors
      have developed a new valve-mechanical model of urinary tract function. A
      comprehensive mechanical hypothesis is also presented, integrating the role of
      peristalsis. CONCLUSIONS: The authors believe that the new theory enhances
      previous knowledge. From a structural point of view, the urinary tract may be
      considered to consist of dualvalves. The dual-valve mechanism combined with
      peristalsis allows better explanation of the function of the upper urinary tract
      in particular. The main conclusion is that the flow in the urinary tract must be
      studied integrally within the body. This new theory does not contradict well
      known and acknowledged theories, and moreover, it may help solve certain medical
      problems.

PMID- 24578879
TI  - The calpain system as a potential target for pelvic muscle reinforcement.
AB  - The fascial and muscular components within the pelvic floor create a support
      mechanism that facilitates storage and voiding of urine. Their constituents are
      mainly fibrillar collagens I and III, which are responsible for maintaining
      tensile strength. Stretching and recoiling is enabled by the elastic fibers
      consisting of elastin on a scaffold of microfibrils, fibrillin-1 and -2. Calpains
      are intracellular Ca2+ -dependent cysteine proteases found in almost all
      eukaryotes and some bacteria. Calpains display limited proteolytic activity at
      neutral pH, proteolyzing substrates to transform and modulate their structures
      and activities, and are therefore called "modulator proteases". By making
      selective limited proteolytic cleavages, they modulate the activity of enzymes,
      including key signaling molecules, and induce specific cytoskeletal
      rearrangements, accounting for their roles in signal transduction and structural
      stabilization. Understanding these mechanisms should provide avenues for novel
      therapeutic strategies to treat pathological processes such as urinary
      incontinence and pelvic prolapse. 

PMID- 24578882
TI  - Salvage open radical prostatectomy after failed radiation therapy: a single
      center experience.
AB  - INTRODUCTION: Currently there is no universally accepted approach for the
      management of radiation-recurrent prostate cancer. The aim of this study was to
      detail our experience performing salvage radical prostatectomy for patients who
      failed primary treatment of prostate cancer with radiation therapy. MATERIAL AND
      METHODS: We retrospectively queried our institutional database of radical
      prostatectomy cases for patients who underwent salvage surgery for radiation
      recurrent prostate cancer. Patients were assessed for the risk of complications
      and oncologic outcomes following salvage surgery. RESULTS: Twenty-four patients
      with a mean age of 65 years (range 51-74) underwent salvage radical
      prostatectomy. Fourteen of these patients (58%) received androgen deprivation
      therapy prior to surgery. Intraoperatively, mean blood loss was estimated at 415
      mL (range 100-1000) and 19 (79%) patients received autologous blood. No patient
      required an allogeneic transfusion or experienced a rectal injury. Postoperative
      bladder neck contracture and urinary incontinence developed in 17% and 39% of
      men, respectively. Two (29%) of seven patients remained potent after salvage
      surgery. No patient developed a fistula. Overall and recurrence-free survival at
      5-years was 90% and 39%, respectively. On multivariate analysis, extracapsular
      extension was the only significant predictor of biochemical recurrence (HR 6.9,
      95% CI 1.9-25.3 p = 0.003). CONCLUSION: In carefully selected patients, salvage
      radical prostatectomy for radiation-recurrent prostate cancer is a treatment
      option with acceptable oncologic outcomes and a moderate complication rate.

PMID- 24578881
TI  - Is there a link between soft drinks and erectile dysfunction?
AB  - This review focuses on the potential role of soft drinks, particularly the sugar
      component, in the pathogenesis of erectile dysfunction (ED). We analyzed the
      hypothetical link between metabolic disorders, induced by sweetened soft drinks
      overconsumption, and ED. High caloric intake, high refined-carbohydrates, and
      high fructose corn syrup (HFCS) content and less satiety are main factors
      responsible for metabolic disorders contributing to ED development. Regular diet
      mistakes among human males, such as soft drink consumption, may lead to slow and
      asymptomatic progression of ED, finally resulting in full claimed manifestation
      of ED. 

PMID- 24578883
TI  - Radical or simple nephrectomy in localized renal cell carcinoma: what is a
      choice?
AB  - INTRODUCTION: Renal cell carcinoma (RCC) accounts for approximately 3% of all
      adult malignancies. Surgery remains the only effective method of renal tumors
      treatment. In fact, for advanced RCC, radical nephrectomy (RN) should remain a
      standard treatment. However, in localized RCC (LRCC) a real increase of survival
      rates realized by RN compared with simple nephrectomy (SN) or organ-sparing
      surgery is discussable. The aim of our study was to assess the impact of
      nephrectomy type on the prognosis of LRCC treatment. MATERIAL AND METHODS: We
      analyzed the long-term outcomes of RN (n = 248 pts.) and SN (n = 170 pts.) in 418
      pts. with LRCC. There were no significant statistical differences in tumor
      stages, age stratification or gender between these two groups. To compare the
      efficacy of RN and SN we determined overall survival (OS) and cancer-specific
      survival (CSS) rates in both divided groups. The 3-year OS in RN group was 93.1%
      vs. 91.8% in SN group. RESULTS: CSS rates after the same period were 96.8% vs.
      94.7% respectively. The 5-year OS in RN group was 91.5% vs. 88.8% in SN group.
      After 5 years of follow-up, CSS in RN group was 94.4% vs. 92.4% in SN group. Type
      of nephrectomy does not influence on LRCC outcomes. The 3- and 5-year overall
      survival rates and cancer-specific survival rates in RN and SN group were almost
      identical. CONCLUSION: Hence, if radical nephrectomy does not ensure better
      survival than simple nephrectomy, the expediency of vast surgery in localized RCC
      is doubtful.

PMID- 24578884
TI  - Tranexamic acid decreases blood loss during transurethral resection of the
      prostate (TUR -P).
AB  - INTRODUCTION: Postoperative blood loss after prostate surgery is thought to be
      associated with an increase in urinary fibrinolytic activity. Tranexamic acid
      (TXA) is both a potent inhibitor of plasminogen and urokinase activators and a
      low molecular weight substance that is excreted unchanged in the urinary tract
      and can be administered both orally and intravenously. We investigated the effect
      of TXA on the amount of blood loss during transurethral resection of the prostate
      (TURP). MATERIALS AND METHODS: Forty patients with registry numbers ending in
      even numbers were allocated to the treatment group; those ending in odd numbers
      were used as controls and received no treatment. The treatment group received 10
      mg/kg TXA by intravenous infusion during the first half hour of the operation,
      while the control group of patients received no medication. Serum hemoglobin was
      measured before and after surgery. The volume and hemoglobin concentration of the
      irrigation fluid, resected prostate weight, and duration of resection were
      recorded. RESULTS: The mean loss of hemoglobin per gram of resected prostate
      tissue was 1.25 g in the TXA group and 2.84 g in the control group. Total
      hemoglobin loss in the irrigating fluid and hemoglobin loss per 1 gram of
      prostate tissue was lower in the group of patients given TXA than in the control
      group (p = 0.018 and p <0.001). CONCLUSION: Reduced bleeding during TURP as a
      result of TXA treatment may lead to better surgical conditions and, as a
      consequence, shorter operative times and lower irrigating fluid volumes.

PMID- 24578885
TI  - Operative shortening of the sling as a second-line treatment after TVT failure.
AB  - INTRODUCTION: Stress urinary incontinence (SUI) is defined as an involuntary loss
      of urine during physical exertion, sneezing, coughing, laughing, or other
      activities that put pressure on the bladder. In some cases, recurrent or
      persistent SUI after sling operations may be caused by too loose placement of the
      sling. In the current study, we describe our method of shortening of the sling as
      a second-line treatment of tension-free vaginal tape (TVT) failure. MATERIALS AND
      METHODS: Four women, aged 46-61, after initial TVT operation were treated for
      persistent SUI. The severity of SUI was estimated by: physical examinations,
      cough tests, 24-h pad tests, and King's Health Questionnaire. The shortening
      procedure, based on excising the fragment of tape and suturing it back, was
      performed in all patients. RESULTS: All cases achieved a good result, which was
      defined as restoration of full continence. No complications occurred. The 12
      month follow-up showed no side-effects. The postoperative control tests: the
      cough and 24-h pad tests were negative in all women. The general health
      perceptions increased after the shortening procedure by a mean value 44.25%. The
      incontinence impact decreased by a mean value 44.6%. In all patients, role and
      physical limitations significantly decreased (by 88.5% and 80.5%, respectively).
      The negative emotions connected with SUI significantly decreased after the second
      procedure. CONCLUSIONS: The operative shortening of the implanted sling is a
      simple, cheap, and effective method of second-line treatment in cases of TVT
      failure and may be offered to the majority of patients with insufficient urethral
      support after the first procedure.

PMID- 24578886
TI  - Detection of loss of heterozygosity in patients with urinary bladder carcinoma:
      neoplastic tissue vs. urine sediment cells.
AB  - INTRODUCTION: Loss of heterozygosity (LOH) is frequently observed in urinary
      bladder neoplasms. In the reported study, an attempt was undertaken to determine
      the loss of heterozygosity of TP53(17p13), RB1(13q14), CDKN2A/ ARF(9p21) genes in
      DNA from neoplastic tissue, collected from patients with diagnosed urinary
      bladder carcinoma, and to compare the results with those of LOH evaluation in DNA
      isolated from urine sediment cells. MATERIAL AND METHODS: After isolation, DNA
      was amplified (PCR) by means of primers to five polymorphic microsatellite
      markers, the products being then separated on agarose gel. Following the method,
      a total of 125 DNA samples were obtained, isolated from neoplastic cells,
      together with 125 corresponding DNA samples, isolated from urine sediment cells.
      RESULTS: The loss of heterozygosity in at least one marker was identified in
      39.2%. (49/125) of DNA from studied tumors and in 34.3% (43/125) of DNA samples,
      isolated from urine sediment cells. An analysis of LOH from the DNA, isolated
      from urine sediment cells, allowed for identification of 81.8% of neoplastic
      tumors with 99.7% specificity. CONCLUSIONS: Our observations have demonstrated
      that LOH within 13q14, 17p13 and 9p21 loci is more often observed in clinically
      more advanced neoplasms. LOH in 17p13 locus is more frequently found in tumors at
      high histopathological stage, while in low-stage neoplasms, LOH is most often
      observed on chromosome 9. The high sensitivity (81.8%) and specificity (99.7%) of
      LOH studies in DNA, isolated from urine sediment cells, make this technique an
      advantageous, non-invasive method for detection and screening of bladder cancer.

PMID- 24578887
TI  - Significance of CDKN2A gene A148T variant in patients with bladder cancer.
AB  - OBJECTIVES: The A148T polymorphism of CDKN2A gene is observed in various
      neoplasms with the incidence rate of 3-35%, however, rather little is known
      either about the frequency of its occurrence or of its significance in urinary
      bladder carcinoma. MATERIALS AND METHODS: DNA was isolated from blood of 156
      patients with urinary bladder carcinoma (130 men). In histopathology, 84 cases
      were classified as G1, 42 as G2, and 30 as G3. The clinical stage was in 81 cases
      estimated at Ta and in 75 cases at T1-T4. A148T polymorphism was detected by the
      MSSCP technique and by sequencing. RESULTS: A148T polymorphism was identified in
      9/156 urinary bladder carcinoma cases (only in men). The obtained results were
      compared with the polymorphism incidence for the Polish population, estimated by
      Debniak et al. The occurrence in the group of the bladder cancer patients turned
      out higher (5.77%) from that in the control group (2.89%) (G test, table 2*2:
      NBLADDER CANCER = 156, NCONTROL = 1210, G = 4.298, p <0.05). CONCLUSION: Summing
      up and taking into account the analysis of clinical parameters and the age of the
      disease occurrence, the A148T polymorphism of CDKN2A gene was identified in the
      study group only in men, in whom the disease was diagnosed above the age of 60,
      while the diagnosed neoplasms were in the majority of cases characterized by
      higher clinical stages and higher grades of malignancy. This has been the first
      study that attempted to show a potential association between A148T alterations
      and an increased risk for bladder cancer development.

PMID- 24578888
TI  - Effect of ALA-mediated photodynamic therapy in combination with tumor necrosis
      factor-related apoptosis-inducing ligand (TRAIL) on bladder cancer cells.
AB  - INTRODUCTION: Photodynamic therapy (PDT), an alternative treatment modality for
      superficial bladder tumors is based on the interaction of a photosensitizer with
      light. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a
      promising candidate for anticancer therapy due to its ability to selectively
      induce apoptosis in cancer cells. However, not all tumor cells are sensitive to
      TRAIL. TRAIL-resistant cancer cells can be sensitized to TRAIL induced apoptosis
      by anticancer agents. OBJECTIVE: We investigated the combined cytotoxic effect of
      TRAIL and PDT with 5-aminolevulinic acid (ALA) on bladder cancer cells. MATERIALS
      AND METHODS: THREE HUMAN BLADDER TRANSITIONAL CANCER CELL LINES: T24, 647V, and
      SW780 were treated with TRAIL and/or ALA-mediated PDT. Cytotoxicity was
      determined by MTT and LDH assay. RESULTS: Our study confirmed that T24 and 647V
      bladder cancer cells were resistant to TRAIL, whereas SW780 cells were sensitive
      to TRAIL. We therefore examined the cytotoxic effect of TRAIL in combination with
      ALA-mediated PDT on bladder cancer cells. We showed for the first time that
      pretreatment with low dose of PDT significantly sensitizes bladder cancer cells
      to TRAIL induced cytotoxicity. CONCLUSION: ALA-mediated PDT augments the
      cytotoxic effect of TRAIL on transitional cancer cells of bladder. The obtained
      results suggest that combined treatment of TRAIL and PDT may provide the basis
      for a new strategy to induce cytotoxicity in bladder cancer cells.

PMID- 24578889
TI  - Retroperitoneoscopic ureterocutaneostomy as a method of urinary diversion in case
      of complicated urinary fistula after radiotherapy.
AB  - The case of 71-year-old woman with massive vesicovaginal and recto-vaginal
      fistula after radiotherapy treated with bilateral laparoscopic
      ureterocutaneostomy is presented. A retroperitoneoscopic access was applied. The
      technical aspects of the procedure are described. The interdisciplinary character
      of this not so rare problem is underlined. In our opinion this kind of procedure
      may be considered as a valuable alternative for commonly used methods of urine
      deviation. 

PMID- 24578890
TI  - Urethral diverticulum presenting as a scrotal mass in a paraplegic male: Report
      of a case and review of the literature.
AB  - Male urethral diverticula are rare and can be congenital or acquired. We report a
      case of acquired urethral diverticulum presenting as a scrotal mass in a
      paraplegic male. On physical examination, the scrotal mass mimicked a primary
      intrascrotal lesion. However, on retrograde urethrography, the correct diagnosis
      was made. The patient had a small incontinent spastic bladder with a history of
      prolonged catheterization. Eventually, the urethral diverticulum was excised
      including the affected segment of bulbous urethra. Pathologic examination
      revealed the diverticulum wall lined by granulation and chronic inflammatory
      tissue. 

PMID- 24578891
TI  - Large tunica albuginea cyst mimicking a large hydrocele with a unique ultrasound
      feature.
AB  - A 58-year-old man presented with a large left scrotal swelling suspected to be a
      large hydrocele, both, clinically and on initial ultrasound. However, at
      operation, a large tunica albuginea cyst was found arising from the mid anterior
      wall of the tunica albuginea. It was dissected, excised and edges under run.
      Further review of the ultrasound scan revealed a unique feature of large tunica
      albuginea cyst simulating a hydrocele. 

PMID- 24578892
TI  - Prostate cancer stem cells.
AB  - The Cancer Stem Cells (CSCs) hypothesis postulates that a minute subpopulation of
      cells is accountable for cancer initiation and progression. Unlike the stochastic
      and clonal evolution models, the CSC theory proposes that tumours are
      hierarchical and only the rare subset of cells at the top of the 'stemness
      hierarchy tree' are adequately 'equipped' biologically to initiate and drive
      tumourigenesis. CSCs have been implicated in various solid malignancies including
      prostate cancer (PCa), where their existence seems to provide an explanation for
      the failure of tumour eradicating therapies. As CSCs are thought to share many
      properties with normal stem cells, understanding normal stem cells should shed
      light on the pathomechanisms of cancer and, importantly, on potential therapeutic
      interventions. The purpose of this paper is to review the existing data on CSCs
      in PCa, their putative phenotypic markers, potential role in tumour biology and
      relevance to therapy. 

PMID- 24578893
TI  - Reciprocal cross-talk between Prostaglandin E2 and bone in prostate cancer: a
      current review.
AB  - In this review we analyzed the role of PGE2 as a possible regulator of bone
      metabolism and bone metastases in prostate cancer. Published studies were
      identified by searching computerized bibliographic systems from January 1(st),
      2000 to July 1(st), 2011. PGE2 represents a key factor in the modulation of bone
      metabolism and bone metastatic disease in prostate cancer interacting with bone
      regulatory signals including the RANK/RANKL/OPG system and Wnt pathways. A high
      concentration of PGE2 exerts a prevalent stimulatory effect on osteoclastogenesis
      via OPG/RANK/RANKL axis activation and a inhibitory effect on osteoblastogenesis
      trough inhibition of Wnt pathway. An inversely low level of PGE2 exerts a
      stimulatory effect on osteoblastogenesis via activation of the Wnt pathway. Our
      finding suggests that PGE2 acts as a regulator in maintaining normal bone mass
      and indicate a mechanism whereby chemical manipulation of PGE2 levels or
      signaling may be therapeutically beneficial for prostate cancer treatment. 

PMID- 24578894
TI  - Factors predicting Gleason score 6 upgrading after radical prostatectomy.
AB  - OBJECTIVES: Prostate cancer Gleason score 6 is the most common score detected on
      prostatic biopsy. We analyzed the clinical parameters that predict the likelihood
      of Gleason score upgrading after radical prostatectomy. METHODS: The study
      population consisted of 241 patients who underwent radical retropubic
      prostatectomy between Feb 2002 and Dec 2007 for Gleason score 6 adenocarcinoma.
      The influence of preoperative parameters on the probability of a Gleason score
      upgrading after surgery was evaluated using multivariate logistic regression and
      ROC curves. RESULTS: Gleason score upgrade was found in 92 of 241 patients
      (38.2%). Multivariate logistic regression analysis showed that only percentage of
      cancer in dominant lobe and prostate weight were significant predictors for
      Gleason score upgrading (p = 0.043 and p = 0.006, respectively). ROC curves
      showed that prostate weight and PSA density were only two independent significant
      parameters for prediction of upgrade (AUC - 0.634, p <0.0001 and 0.604, p =
      0.006, respectively). Gleason score upgrading was observed to be accompanied by
      significantly higher rates of extra prostatic extension (p <0.001) and seminal
      vesicle invasion (p = 0.002). CONCLUSIONS: Almost forty percent of tumors graded
      Gleason 6 at biopsy are Gleason 7 at surgery. Upgraded tumors significantly
      associated with adverse pathological features. The probability of Gleason score
      upgrade can be predicted using prostate weight and PSA density as independent
      parameters.

PMID- 24578895
TI  - Outcome of surgery in locally advanced pT3a prostate cancer.
AB  - INTRODUCTION: The aim of this study is to present the oncologic outcomes and to
      determine prognostic parameters of overall (OS), cancer specific survival (CSS),
      disease progression free survival (DPFS) and biochemical progression free
      survival (BPFS) after surgery for pT3a prostate cancer (PCa). MATERIAL AND
      METHODS: Between 2002 and 2007, a pT3a stage after radical prostatectomy was
      detected in 126 patients at our institution. Kaplan-Meier analysis was used to
      calculate OS, CSS, DPFS and BPFS. Cox regression was used to identify predictive
      factors of survival. RESULTS: Five-year OS, CSS, DPFS and BPFS rates were 96%,
      98.7%, 97.3% and 60%, respectively. Among patients with prostate specific antigen
      (PSA) <10 ng/ml and PSA >20 ng/ml the 5-year OS was 98.8% and 80%, respectively,
      whereas 5-year BPFS was 66% and 16.6%, respectively. Survival was different when
      comparing surgery Gleason score <=7 and >=8. 5-year OS and BPFS were 98% vs. 80%,
      and 62.6% vs. 27.3%, respectively. Specimen Gleason score and preoperative PSA
      were significant predictors of BPFS. The risk of biochemical progression
      increased up to 2-fold when a Gleason score >=8 was present at final pathology.
      CONCLUSIONS: In locally advanced pT3 PCa, surgery can yield very good cancer
      control and survival rates especially in cases with PSA <10 ng/ml and Gleason
      score <=7. PSA and Gleason score after surgery are the most significant
      predictors of outcomes after radical prostatectomy.

PMID- 24578896
TI  - Urinary incontinence after radical prostatectomy - experience of the last 100
      cases.
AB  - Radical prostatectomy (RP) is a recognized treatment method of organ-confined
      prostate cancer. Among post-surgery complications, urinary incontinence is a
      major one. The aim of this study was to determine the incontinence rate after RP
      and to analyze factors that might affect it. Between March 2007 and December
      2008, 132 RP's were performed at Warsaw Cancer Center. A questionnaire to assess
      the condition before and after RP was developed by the authors and sent to all
      treated patients. The questionnaire focused on health status information,
      function in urinary domain, rate of returning to "normal" activity level as
      before RP and satisfaction from the treatment. The median age of patients was 62
      years. Out of 132 patients 102 subjects (77.2%) responded to the questionnaire.
      Of all responders, 35 patients (34.3%) reported total urinary continence after
      RP. After RP 35(34.3%) patients reported total urinary continence and in
      55(53.9%) patients urinary incontinence of medium degree was present. In 12
      (11.8%) patients significant urinary incontinence developed. The most common
      cause of urine dripping (82% of patients with any degree of urinary incontinence)
      was associated with abdominal muscle pressure. No statistically significant
      association between urinary incontinence and adjuvant radiotherapy after RP or
      the surgeon performing the RP was found (>0.79, >0.803). Radical prostatectomy
      carries a certain risk of complications. We observed an 88.2% rate of significant
      (total and moderate degree) urinary continence. The adjuvant radiotherapy and
      surgeons, who performed the RP, did not affect the rate of incontinence. 

PMID- 24578897
TI  - The impact of adjuvant therapy in patients with biochemical recurrence on
      prostate cancer progression and mortality five years after radical prostatectomy.
AB  - INTRODUCTION: The clinical significance of biochemical recurrence (BCR) after
      radical prostatectomy (RP) due to prostate cancer (PCa) is not unambiguous,
      sometimes being independent from the real progression. BCR is followed by a
      greater risk of adverse events and almost always results with the necessity for
      implementation of adjuvant therapy (AT). The aim of the following study was to
      examine the impact of AT in patients with BCR together with PCa progression and
      mortality 5-years after RP. MATERIAL AND METHODS: Two hundred forty-seven
      patients after RP, who were treated in the period from 1995 to 2009, underwent
      the retrospective analysis. They were divided into three groups according to the
      applied AT after prior BCR diagnosis. The first group (n - 39) included patients
      treated with radiotherapy, along with hormonotherapy. The second group (n - 63)
      covers patients receiving hormonotherapy only. The third group (n - 145) consists
      of patients without BCR. Five-year general and disease-specific survival was
      evaluated and choice prognostic factors were compared. RESULTS: Five-year overall
      survival was 74.2% in group I, 88.3% in group II, and 98.7% in group III.
      Diseasespecific survival was: 76.9%, 90.5%, and 100% (p = 0.001), respectively.
      BCR was diagnosed in 102 (41.5%) patients; while in another 24 (23.5%) of them
      progression was diagnosed after the AT was applied. CONCLUSIONS: The risk of BCR
      5-years after RP is greater in patients with high initial concentration of PSA,
      higher Gleason score, and clinical advancement. Five-year overall and disease
      specific survivals are higher among patients after hormonotherapy alone compared
      to those after both radio- and hormonotherapy.

PMID- 24578898
TI  - Impact of positive surgical margins on biochemical relapse after radical
      retropubic prostatectomy (RRP).
AB  - INTRODUCTION: RP (radical prostatectomy) technique continues the major treatment
      option for men with potential cure and life expectancy exceeding 10 years. The
      aim of the study is to assess the impact of PSM on BR (biochemical relapse), to
      identify PSM risk factors, to clarify the factors involved in BR in the absence
      of PSM. MATERIAL AND METHODS: Consultation of 171 medical-records from patients
      submitted to RRP (radical retropubic prostatectomy) between January/2000
      December/2005. Mean-age: 64 yr. Mean - PSA (positive surgical margin): 11.88
      ng/ml. Clinical staging: 67.8% cT1, 32.2% cT2. GS: <=6 (66.1%), =7 (21.1%), 8-10
      (12.3%). PS: pT0 1.2%, pT2 50.3%, pT3a 36.3%, pT3b 12.9%, pT4 0.6%. pathological
      Gleason score: <=6 39.2%, =7 40.9%, 8-10 19.3%. RB definition was PSA >=0.2
      ng/ml. Adjusted Odds-Ratios with 95% confidence intervals (CI) were estimated
      through univariate logistic regression. RESULTS: There were PSM in 46 specimens,
      28 had single PSM and 18 multiple PSM (>=2). BR occurred in 57 patients (33.3%),
      with an average time after surgery of 23.5 months - 26 patients had PSM and 31
      had not. Statistical significant results for BR in variables PSA, PS and PSM.
      Quadruples if PSM (p <0.0001), triples in single PSM (p = 0.01) and is 6x higher
      in multiple PSM (p = 0.001). Regarding factors that influence the presence of
      PSM, only PS >=pT3a reach statistical significance (p <0.0001). Patients with BR
      but without PSM (54.38%), variables statistically significant were: initial PSA
      >10, (p = 0.029) and pathological Gleason score >=8 with a risk nearly 4x higher
      than pathological Gleason score <=6 (p = 0.027). CONCLUSIONS: Statistical risk
      analysis concluded that the presence of PSM in RRP is strongly influenced by PS
      >=pT3a. The presence of PSM and their number increase significantly the risk of
      BR compared to other factors. In the absence of PSM, the factors that seem to be
      crucial and with greater impact on BR are initial PSA>10 and pathological Gleason
      score >=8.

PMID- 24578899
TI  - Credibility of a smoking questionnaire based on urine cotinine level for patients
      with bladder cancer - a preliminary report.
AB  - An analysis of the reliability of a questionnaire on smoking in 96 patients with
      transitional cell carcinoma (TCC) of the bladder. The credibility of the
      questionnaire was evaluated based on the detection of cotinine, an objective
      marker of tobacco smoke exposure, in urine. It was confirmed that approximately
      18% of smokers did not admit to smoking, did not comply with recommendations to
      stop smoking, and about 4% of non-smokers were exposed to tobacco smoke
      unknowingly. 

PMID- 24578900
TI  - Efficacy of combination therapy with tamsulosin and zolpidem on nocturia in
      patients with benign prostatic hyperplasia.
AB  - INTRODUCTION: We examined the efficacy of combination therapy with alpha1-blocker
      tamsulosin and hypnotic zolpidem in patients who had suffered from sleep
      disturbance associated with nocturia. MATERIAL AND METHODS: A total of 35
      patients diagnosed with nocturia with lower urinary tract symptoms (LUTS)
      suggestive of benign prostatic hyperplasia (BPH) were studied. After treatment
      with tamsulosin for 4 weeks, 16 patients dissatisfied with nocturia
      (nocturiaquality of life index >=4) and suspected to have sleep disturbance
      (Athens Insomnia Scale >=6) received additional treatment with tamsulosin and
      zolpidem for 2 weeks. Outcomes were evaluated by the International Prostate
      Symptom Score (IPSS) and quality of life index (QOL), Athens Insomnia Scale (AIS)
      and nocturia-quality of life index (nocturia-QOL). RESULTS: After monotherapy
      with tamsulosin, significant reductions in IPSS (18.9 +/-3.8 to 9.9 +/-3.0, p
      <0.001), QOL (4.5 +/-0.9 to 3.2 +/-0.9, p <0.001) and nocturia episodes (3.4 +/
      0.7 to 2.6 +/-1.0, p <0.001) were observed. However 20 patients were dissatisfied
      with nocturia (nocturia- QOL >=4). Among 20 patients, 16 patients were suspected
      to have sleep disturbances (AIS >=6). In these patients, additional therapy with
      tamsulosin and zolpidem significantly reduced nocturia episodes (3.3 +/-0.8 to
      1.9 +/-0.7, p <0.001), AIS (10.6 +/-2.9 to 6.8 +/-25, p <0.001) and nocturia -
      QOL (5.6 +/-0.5 to 3.6 +/-1.1, p <0.001) compared with patients after treatment
      with tamsulosin only. CONCLUSIONS: Combination therapy with tamsulosin and
      zolpidem may be useful for patients with BPH dissatisfied with nocturia and
      suspected to have sleep disturbance.

PMID- 24578901
TI  - Vesicourethral anastomosis using V-LocTM barbed suture during robot-assisted
      radical prostatectomy.
AB  - In Europe, localized prostate cancer (PCa) is increasingly treated by robot
      assisted radical prostatectomy. This minimally invasive procedure is technically
      evolving, with benefits to both the patient and surgeon. One of the final steps
      of the operation is the formation of a watertight vesicourethral anastomosis
      (VUA). A suboptimal anastomosis can lead to serious consequences, including acute
      urinary leak, ileus, prolonged hospitalization and catheterization, urethral
      stricture, and urinary incontinence. It is therefore highly desirable to develop
      a simple, reproducible and dependable technique for VUA formation. We report a
      VUA formation technique using a unidirectional barbed suture (3-0 V-LocTM 180
      absorbable suture, Covidien, Dublin, Ireland). 

PMID- 24578902
TI  - Bladder augmentation and continent urinary diversion in boys with posterior
      urethral valves.
AB  - Posterior urethral valve (PUV) is a condition that leads to characteristic
      changes in the bladder and upper urinary tract. Dysfunction of the bladder such
      as a hyperreflective, hypertonic, and small capacity bladder as well as sphincter
      incompetence and/or myogenic failure should be adequately treated. Poor
      compliance/small bladder could be treated with anticholinergics, but bladder
      augmentation will probably be indicated. Although bladder reconstruction with
      gastrointestinal segments can be associated with multiple complications,
      including metabolic disorders, calculus formation, mucus production, enteric
      fistulas, and malignancy formation, enterocystoplasty is still the gold standard.
      In contrast to a neuropathic or exstrophic bladder, augmentation of the valve
      bladder allows spontaneous voiding without significant residual urine in the
      majority of cases, but some require CIC (clean intermittent cathterization).
      Augmentation cystoplasty is also an efficient approach in those children who will
      require kidney transplantation in the future. 

PMID- 24578903
TI  - Pediatric single port transumbilical nephrectomy and nephroureterectomy.
AB  - OBJECTIVE: To present seven cases of single incision laparoscopic nephrectomy and
      nephroureterectomy in children as a recent videoscopic innovation. PATIENTS AND
      METHODS: Seven children with nonfunctioning kidneys, three with multicystic
      dysplastic kidneys, two with end-stage renal nephropathy due to vesicoureteral
      reflux, and two with giant hydronephrosis were qualified to nephrectomy or
      nephroureterectomy. The surgery was performed transperitoneally using single
      incision access laparoscopy. The operative time was in the range of 50-90 min.
      RESULTS: There were no intraoperative or postoperative complications. The
      patients were discharged on the third postoperative day. The incision scars were
      hidden inside the umbilicus. CONCLUSIONS: Nephrectomy or nephroureterectomy using
      a single transumbilical port in children is a feasible and efficacious technique.
      The advantages are shortened convalescence, excellent cosmetic results, and
      reduction of potential wounds complications. However, clear indication of single
      site laparoscopic procedures in children remains to be clarified.

PMID- 24578904
TI  - Analysis of 1,000 cases of synthetic midurethral slings used for treatment of
      female urinary incontinence - a single-center experience.
AB  - INTRODUCTION: This study summarized our experience in the treatment of 1,081
      women with stress urinary incontinence (SUI) using mid-urethral slings. MATERIAL
      AND METHODS: The study included 1,081 operated patients. Pure SUI was diagnosed
      in 77.80% (841) of the patients; another 18.68% (202) had mixed symptoms. The
      remaining 3.52% (38) suffered from recurrent SUI. Group 1 included the SUI
      patients treated with TVT. Group 2 - SUI managed with TVT-O. In Group 3, mixed
      urinary incontinent (MUI) patients were treated with TVT-O. RESULTS: Retropubic
      TVT was used in 273 patients (25.25%) and TVT-O in 740 (68.45%). Other slings
      were used in 68 patients (6.3%). Mean follow-up for the groups was 50.1, 31.1,
      and 32.6 months respectively. For objective evaluation of cure rate we used the
      cough stress test. Subjective efficacy was studied via a visual analog scale. The
      complication rate in each group of the patients was used as a secondary end
      point. A negative cough test was found in 85.58% of patients in Group 1. For the
      TVT-O group, the objective cure rate was 84.36%. Intra-operative complications
      for TVT and TVT-O were not related to age, BMI, or parity. Bladder perforation
      and pelvic hematoma developed more frequently in the TVT group. There is a higher
      risk of vaginal perforation for TVT-O. The objective and subjective cure rates
      for MUI patients were 86.15% and 87.69% respectively. CONCLUSIONS: TVT and TVT-O
      are equally effective and safe methods of treatment for women suffering from SUI
      and MUI.

PMID- 24578905
TI  - Immunohistochemical detection of angiotensin AT 1 and AT 2 receptors in prostate
      cancer.
AB  - INTRODUCTION: The human prostate gland contains all the compounds of the renin
      angiotensin system (RAS), including AT1 and AT2 angiotensin receptors. The role
      of local RAS in the prostate pathology is recently discussed. The aim of the
      present study was the evaluation of AT1 and AT2 expressions in human prostate
      cancers. MATERIAL AND METHODS: The investigation was performed in 20 paraffin
      embedded needle biopsy specimens from routine diagnostic prostate cancer
      biopsies. The specimens were stained with hematoxylin and eosin and immunostained
      with anti-AT1 and anti-AT2 antibodies. For visualization of primary antibodies,
      the streptavidin-biotin-peroxidase technique was applied. The expression of both
      receptor proteins was evaluated quantitatively using image analysis method.
      RESULTS: The positive immunostaining with both anti- AT1 and anti-AT2 antibodies
      can be found in stromal as well as epithelial structures. The results of
      quantitative evaluation showed the positive correlation between AT1 and AT2
      expressions in neoplastic epithelium and overexpression of both AT1 and AT2 in
      neoplastic epithelium of Gleason grade 2, but not in cancerous structures of
      Gleason grades 3-5. CONCLUSIONS: The data on AT1 and AT2 receptor expressions may
      suggest the involvement of RAS in prostate cancerogenesis. Moreover, the
      persistence of AT1 receptors in prostate cancer speaks in favor of attempts to
      use of AT1 receptor blockers (i.e. sartanes) and/or AT2 agonists in prostate
      cancer prophylaxis and/or treatment.

PMID- 24578906
TI  - Prostate epithelial stem cells are resistant to apoptosis after alpha1-antagonist
      treatment. The impact for BPH patients.
AB  - INTRODUCTION: Induction of apoptosis in prostatic epithelial cells by doxazosin,
      terazosin and prazosin has been well documented. However, the biochemical
      pathways of doxazosin action is still unclear. Aforementioned drugs should lead
      to decrease of prostate volume, although this effect was never observed in
      patients suffering from BPH after treatment with alpha1-antagonists. Probably, it
      is connected with cancer stem cells' resistance on chemotherapeutic agents. The
      aim of this study was to compare incidence of apoptosis induced by doxazosin in
      progenitor and differentiated cells isolated from human prostate epithelium.
      MATERIAL AND METHODS: For this purpose tissue specimens were obtained from 10
      patients suffering from BPH, the primary cultures of prostate epithelium were
      established and CD133 MicroBeads sorting was prepared. Both, CD133(+)/CD133(-) co
      cultures and CD133(+) cells were incubated with different concentration of
      doxazosin for 12 h. Cell viability and apoptosis was estimated with Annexin V
      FITC. RESULTS: 12 h incubation of CD133(+)/CD133(-) co-cultures with doxazosin
      resulted in increase of apoptotic cells, while in CD133(+) cultures no changes
      were observed. Correlation between apoptotic cell number and doxazosin
      concentration in CD133(+)/ CD133(-) co-cultures group was high (R = 0.99).
      CONCLUSION: Doxazosin induced apoptosis in co-cultures of progenitor and
      differentiated epithelial cells. However, progenitor cells were not susceptible
      to apoptosis, what can be a reason of treatment failure in BPH patients.

PMID- 24578907
TI  - Intratesticular epidermoid cyst: is radiological diagnosis enough?
AB  - Intratesticular epidermoid cysts are rare solid tumorlike lesions. They
      constitute 1% of all testicular tumors. Major advances have been achieved during
      the last decades, shifting the management of epidermoid cysts to a more
      conservative approach. We present a case of a 20-year-old male who was referred
      to the urology department with a two-year history of a gradually increasing
      painless right-sided scrotal lump. We will discuss the diagnostic work up of
      intratesticular epidermoid cyst, with the operative management and literature
      review. 

PMID- 24578908
TI  - Management of bladder neck leiomyoma during pregnancy.
AB  - A 29-year-old primigravida was admitted to the urology ward with acute urinary
      retention. The patient underwent cystoscopy, MRI (magnetic resonance imaging),
      and tissue biopsy, which consequently led to the diagnosis of bladder neck
      leiomyoma that obstructed urine outflow. Subsequent to a cesarean section, a
      successful transurethral resection was performed. Here the diagnostic complexity
      in the pregnant patient, clinical course, and outcome are described. One year
      after successful treatment both mother and daughter are in good condition. 

PMID- 24578909
TI  - Scrotal hematoma resulting from extracorporeal shock wave lithotripsy for a renal
      calculus: a sign of retroperitoneal hemorrhage.
AB  - We report a rare case of a patient presenting with scrotal hematoma associated
      with retroperitoneal hemorrhage after extracorporeal shock wave lithotripsy
      (ESWL). We propose a mechanism for the formation of scrotal hematoma and its
      importance as a sign of retroperitoneal hemorrhage. 

PMID- 24578910
TI  - Partial segmental thrombosis of the corpus cavernosum.
AB  - The case of a 32-year-old man with perineal pain and local swelling is presented.
      Partial segmental thrombosis of the corpus cavernosum was diagnosed and treated
      conservatively with systemic anticoagulants. Conservative management proved to be
      a safe and successful therapeutic option in partial thrombosis of the corpus
      cavernosum. 

PMID- 24578911
TI  - Primary cancer of the anterior urethra in a male patient.
AB  - We present a 76-year-old male patient, who was diagnosed with transitional cell
      carcinoma (TCC) of the distal part of the urethra. Transurethral resection of the
      tumor (TURT) of the urethra was conducted. After establishing local relapse,
      surgical removal of the distal part of the urethra was proposed to the patient.
      Due to no consent for an open surgery, another electroresection of the tumor was
      performed. When the second relapse occurred, the patient provided his consent for
      surgical removal of the part of the urethra with anastomosis of the remaining
      part of the urethra with the skin from the abdominal part of the penis.
      Postsurgical observation did not reveal any local relapse. 

PMID- 24578912
TI  - PSA mass screening: is there enough evidence?
AB  - Prostate cancer plays an important role in widely understood aspects of men's
      health, and is becoming a growing problem in terms of public life. Prostate
      cancer is one of the most common neoplasms among men. Male patients can live with
      prostate cancer for a long time so it is important to offer appropriate males
      adequate diagnostic tools and treatments. Prostate cancer and PSA potentially
      represent a "pair" of a disease and an appropriate indicator to be used in mass
      screening, but regardless of that there is still active debate about it.
      Extensive use of PSA screening has modified epidemiology of the diseases.
      Randomized controlled studies provided sufficient results regarding a reduction
      in mortality through PSA mass screening, while all agreed on risks of
      overdiagnosis and overtreatment. New and accurate screening tools are necessary,
      along with adequate counseling and risk stratification. 

PMID- 24578914
TI  - Blood loss during laparoscopic radical prostatectomy - is it significant or not?
AB  - INTRODUCTION: The traditional assessment of blood loss during laparoscopic
      radical prostatectomy (LRP) is based on the blood volume collected
      intraoperatively in the suction device bottles. While this method is not perfect,
      analysis of changes in blood cell count (BCC) resulting from LRP is advisable.
      MATERIAL AND METHODS: 71 men were submitted to LRP due to prostate cancer in our
      institution over an 18-month time period. From this group, we isolated 60 men
      with clinically minimal intraoperative blood loss (<200 ml) and included them
      into the study. Mean age of the cohort was 62.8 years. We performed standard BCC
      on the day before and 6 hours after the surgery. At the same time points, we
      measured creatinine serum concentration and calculated eGFR to avoid the data
      misinterpretation resulting from impaired renal function in the postoperative
      period. RESULTS: Statistically and clinically significant differences regarding
      all BCC parameters measured pre- and postoperatively were observed. The number of
      red blood cells, hemoglobin concentration, and hematocrit diminished by 17.5%
      (4.68T/l vs. 3.86T/l, p <0.02), 17.0% (8.93 mmol/l vs. 7.41 mmol/l, p < 0.02),
      and 17.9% (0.429 vs. 0.352, p <0.02), respectively. Simultaneously, renal
      function was stable with no significant change in eGFR (82.9 ml/min/1.73 m^2 vs.
      79.09 ml/min/1.73 m^2, p = 0.28). CONCLUSIONS: Standard LRP brings on a
      significant blood loss. While clinically insignificant, this blood loss seems to
      be as high as approx. 600 ml based on laboratory findings. BCC seems to be a more
      accurate method of intraoperative blood loss estimation compared to measurement
      of blood volume collected intraoperatively in the suction device bottles.

PMID- 24578913
TI  - Stem cells for urinary tract regeneration.
AB  - Regeneration of the urinary bladder is a complicated task, due to organ
      dimensions and diseases (cancer, interstitial cystitis) when autologous bladder
      cells cannot be used. Cancer is the most frequent indication for bladder removal
      (cystectomy). Stem cells can be used with the guarantee of the sufficient cell
      number for the in vitro construction of the urinary bladder wall. Tissue
      engineering techniques hold great promise for regeneration of dysfunctional
      urinary sphincter. Denervation following surgical procedures or injuries results
      in weakness of the urethral sphincter and stress urinary incontinence. Injectable
      therapies and the potential of stem cells for sphincter restoration was presented
      in this review. The aim of this review was to present possibilities of urinary
      bladder regeneration with the use of stem cells and tissue engineering
      techniques. 

PMID- 24578915
TI  - Renal function after nephron-sparing surgery for renal tumors.
AB  - Nephron sparing surgery (NSS) is a technique more frequently utilized in the case
      of surgical treatment of kidney tumor. The aim of the study is to assess renal
      function in patients treated with NSS for renal tumors. Twenty patients, after
      NSS performed for renal tumor, were included in the study. In each patient
      dynamic renal scintigraphy was performed before surgical treatment (test No. 1)
      and after a mean interval of 12 months after surgical procedure (test No. 2). In
      each test renographic curves were evaluated. Creatinine levels and GFR rates were
      also assessed. Mean GFR was 84 ml/min/1.73 m(2) before surgery, and 79
      ml/min/1.73 m(2) after surgical procedure. Mean change of GFR value after the
      surgical procedure was -5.1 (p >0.058). On renography significant deterioration
      of renal function was observed in the operated kidneys of 4 patients (20%) after
      NSS, insignificant deterioration - in four patients (20%) and improvement of
      renal function of operated kidney was found in one patient. In 12 patients (60%)
      no change was observed. The relative percentage GFR-share of operated kidney
      decreased by the average value of 3.8% (p >0.005). Multifactorial analysis did
      not identify significant effect of potential risk factors on the function of the
      kidney subjected to NSS. Preliminary results of this study confirm that
      deterioration of renal function after NSS is a rare event. 

PMID- 24578916
TI  - Normal variants in patients consulted in the Dermatology Clinic for lesions of
      the male external genitalia.
AB  - INTRODUCTION: So far there have been no papers analyzing the incidence of 'non
      pathological' lesions or normal variants on the male external genitalia.
      Subsequently, the number of patients consulted due to the presence of such
      lesions remains unknown. The aim of the study was to estimate the incidence of
      normal variants in patients who were consulted due to lesions on the skin or
      mucosa of the male external genitalia. MATERIAL AND METHODS: The study group
      consisted of 400 males, aged 3-91, who were consulted due to lesions on the
      genitalia in the Department of Dermatology, Venereology and Allergology of the
      Medical University of Gdansk. RESULTS: The most common lesions were
      hyperpigmentation of the median raphe of the penis and scrotum (85.6%), pearly
      penile papules (24%), and prominent veins (24%). Sebaceous hyperplasia or ectopic
      sebaceous glands were revealed in 9% of patients, respectively. Melanocytic nevi
      were diagnosed with similar frequency (9.5%), whereas skin tags more rarely (7%).
      Other 'non-pathological' lesions were diagnosed in a considerably lower number of
      patients. In 32 patients (8% of all patients) the reason of admission to the
      Clinic was just the presence of some 'non-pathological' lesions. Pearly penile
      papules were found to be the most common condition, occurring in 78.1% patients.
      CONCLUSIONS: Normal variants represent a substantial percentage of generally
      asymptomatic lesions and the only indication for their removal is cosmetic
      discomfort or venerophobia.

PMID- 24578917
TI  - Psychological aspect of qualification to implant an artificial urethral sphincter
      AMS 800.
AB  - INTRODUCTION: Implantation of the AMS 800 artificial urethral sphincter is a
      "gold standard" in the treatment of total urinary incontinence in men.
      Appropriate qualification of patients to urinary incontinence treatment
      determines the higher effectiveness of this method. Service of this device
      requires physical fitness and mental efficiency from a patient. MATERIAL AND
      METHODS: The Urological Clinic hospitalized 16 patients, aged from 60 to 80
      years, after first qualification for artificial urethral sphincter implantation.
      Psychological assessment was carried out during anamnesis and medical examination
      using the MMSE and the GDS. RESULTS: Psychological deviations were found in 7 out
      of 16 examined patients, but finally 2 patients were disqualified because of
      their cognitive function disorders with elements of low level depressive syndrome
      (1) and benign cognitive and member function disorders (1). Among the patients
      who were examined by a psychologist: four of them showed mild (3) and temperate
      (1) features of depressive syndrome and one patient showed benign cognitive
      disorder without dementia. However, none of these findings were contraindications
      to incontinence treatment with an artificial urethral sphincter. CONCLUSIONS: 1.
      Mild and temperate features of depression syndrome are not absolute
      contraindications for a sphincter AMS 800 implantation. These patients need only
      pharmacological treatment. 2. Cognitive and other memory disorders are
      contraindications to this method. 3. The qualification to implantation an
      artificial urethral sphincter should include a psychological assessment,
      especially in older patients in whom mental disorders are suspected.

PMID- 24578918
TI  - Endoscopic holmium laser treatment for ureterolithiasis.
AB  - INTRODUCTION: The rapid development and invention of ever more technologically
      advanced ureterorenoscopes as well as other instruments used in fragmenting
      ureteral stones have made the traditional surgical treatment of ureterolithiasis
      very rare. MATERIAL AND METHODS: We investigated 727 patients treated for
      ureterolithiasis. 769 ureteroscopic lithotripsies (URSL) with the holmium laser
      were performed. We evaluated the relation of the stone size, the section of the
      ureter involved, length of time of the stone within the ureter and the condition
      of the urinary tract to the results of the ureterolithiasis treatment. RESULTS: A
      good result of breaking up the stone and passing its fragments out of the ureter
      within 3 months following the first URSL was observed in 642 (90.9%) out of 706
      patients. The remaining 64 (9.1%) patients required additional procedures: ESWL
      was performed on 44 patients; URSL was repeated for 20 patients. The most serious
      early post-URSL complications involved: urinary tract infection with symptoms of
      urosepsis in 10 patients, leading to death in 1 case, ureteral perforation in 3
      patients, including 1 case presenting a periureteral leak that necessitated a
      surgical intervention. CONCLUSIONS: URSL with the holmium laser is an effective
      and safe method for treating ureterolithiasis.

PMID- 24578919
TI  - Large stone clearance in 2-year-old child with staghorn and calyceal stones using
      SWL monotherapy.
AB  - Treatment of pediatric urolithiasis requires a thorough metabolic and urological
      evaluation on an individual basis. The objective of our case report was to
      determine the efficiency and the role of shockwave lithotripsy (SWL) in the
      treatment of pediatric urolithiasis. In this case report we reported our own
      experience in the management of staghorn and calyceal stones in both kidneys with
      SWL. In our case, clearance of multiple staghorn stones and a calyceal stone was
      obtained without any complications after 7 sessions of SWL over 2 months. 

PMID- 24578920
TI  - Ureteroscopy in infants and preschool age children: technique and preliminary
      results.
AB  - INTRODUCTION: We present our experience with the use of semirigid ureteroscopy
      for the treatment of ureteric stones in children less than or equal to 6 years of
      age. MATERIAL AND METHODS: The records of 21 children (12 female, 9 male) with an
      average age of 4.7 years (range 8 months to 6 years) treated with semirigid
      ureteroscopy between June 2006 and July 2010 were reviewed. In 13 ureteral units
      7Fr semirigid ureteroscopy was carried out in a retrograde manner to treat stone
      disease, while an adult ureteroscope (9.5 fr) was used in the remaining patients.
      Stones were located in the upper ureter in 2 cases, middle ureter in 2 cases, and
      lower ureter in 17 cases. Ureteral dilation was not required in all patients.
      RESULTS: Stone size varied from 4 to 13 mm (mean 6 mm). The management of stones
      in 18 (90.7%) children was straightforward and a single ureteroscopy was required
      to clear the ureters. In 2 (6.2%) children, repeat ureteroscopy was undertaken to
      render the ureters stone free, and in 1 child (3.1%) it was not possible to
      remove the stone. Stones were fragmented with pneumatic lithotripsy in 12 cases
      and stones were removed mechanically without fragmentation in the remaining 9
      cases. Intraoperative complications occurred in 2 (9.3%) children and included
      extravasation (1 patient), which was managed with ureteral stenting and stone
      upward migration (1 patient). Early postoperative complications included
      pyelonephritis (1 patient). Mean follow-up was 6.4 (3-36) months. Incidence of
      stricture at the site of stone impaction was not detected in any patients. None
      of the patients managed without a post-operative stent required subsequent
      intervention. CONCLUSIONS: In the hands of an experienced surgeon, ureteroscopy
      in young children can be a safe and efficient treatment for ureteral stones that
      can be performed without ureteral dilation. Routine ureteral stenting is not a
      requirement when the procedure is relatively atraumatic. Further studies and
      longer follow-up are necessary to determine the success of this technique.

PMID- 24578921
TI  - Supernumerary kidney presenting as urinary leakage after an ipsilateral
      laparoscopic radical nephrectomy.
AB  - We present a case of a patient with supranumerary kidney diagnosed after
      laparoscopic radical nephrectomy. Urinary leakage, an unusual complication that
      appeared postoperatively, led to complementary examination and making the right
      diagnosis. The reevaluation of the preoperative CT (computed tomography) in
      enhancement phase and the new CT scan confirmed the presence of a real accessory
      organ connected to the main unit with a small bridge of tissue. The latter right
      nephrectomy was performed. Despite the scarceness of this anomaly, a thorough
      interpretation of images obtained during investigative procedures can provide a
      clue about the presence of this rare entity. 

PMID- 24578922
TI  - Tamoxifen to treat urge-incontinence from an isolated bladder metastasis of a
      primary breast cancer.
AB  - OBJECTIVES: Managing urge-incontinence after metastatic lobular carcinoma of the
      breast into the bladder. MATERIAL AND METHODS: Case report and review of the
      pertinent English language literature. RESULTS: Conservative management with
      tamoxifen resulted in clinical and partial radiological remission and the urge
      incontinence disappeared. CONCLUSION: A conservative mode of treatment is
      possible for metastatic lobular carcinoma of the breast into the bladder.

PMID- 24578923
TI  - Carcinoma in the inactive bladder - the dilemma of the forgotten organ.
AB  - Etiologic factors affecting bladder tumor have been well confirmed and it is
      widely recognized that carcinogenic substances in urine may play an important
      role in a pathogenesis. Carcinoma developing in a defunctionalized bladder,
      although uncommon, does occur. We report a case of a transitional cell carcinoma
      (TCC) found in a remaining bladder of a male patient and a review of the most
      relevant literature. 

PMID- 24578924
TI  - Anastomosing hemangioma with fatty changes of the genitourinary tract: a lesion
      mimicking angiomyolipoma.
AB  - Anastomosing hemangioma of the genitourinary tract is a recently described
      vascular lesion of the kidneys and testes. Although these lesions can occur in
      the renal hilum with infiltration of the hilar adipose tissue, the presence of
      adipocytes in this type of vascular tumor has not been reported. We described a
      case of an anastomosing hemangioma associated with fatty changes of the stromal
      component in a 59-year-old female patient. This unusual morphologic finding not
      only represents a novel curiosity in this rare type of vascular lesion, but also
      could potentially pose significant diagnostic challenges as it is commonly
      mistaken as an angiomyolipoma. 

PMID- 24578925
TI  - Alkaline cystitis - a delayed presentation post transurethral resection of
      prostate. A case discussion and literature review.
AB  - Alkaline encrusted cystitis is a chronic inflammatory condition. It is rare now
      because of appropriate antibiotics. It is a challenging situation with regard to
      its diagnosis and management. We are presenting an interesting case of alkaline
      cystitis post transurethral resection of prostate. The management includes
      careful acidification of urine, curettage of calcified material, and appropriate
      antibiotics. 

PMID- 24578926
TI  - Primary paratesticular carcinoid in a 70-year-old male.
AB  - Carcinoid tumors are neuroendocrine tumors and most frequently occur within
      tissues derived from the embryonic gut. These tumors can occur in any organ but
      are very rare in the paratesticular region. We hereby report a case of
      paratesticular carcinoid in a 70-year-old male who, to the best of our knowledge,
      is the oldest patient reported so far in the world literature. 

PMID- 24578927
TI  - Hypothesis - a congenitally lax pubourethral ligament may be a contributing cause
      of vesicoureteral reflux.
AB  - INTRODUCTION: The hypothesis derives from the field of female stress
      incontinence. Application of pressure on the anterior vaginal wall at midurethra
      with a hemostat restores the geometry of the vesicoureteral junction and
      continence. METHODS: We applied unilateral midurethral pressure during a
      radiological investigation of a 15-year-old female patient who had undergone 2
      surgeries for ureteric reflux. RESULTS: On injection of the dye into the bladder,
      reflux was noted in the left ureter, and this disappeared within 2-3 seconds
      after pressure was applied on 2 successive occasions in the midurethral area of
      the vagina. CONCLUSION: The hypothesis that a musculoelastic mechanism dependent
      on a competent pubourethral ligament may play a role in vesicoureteral valve
      closure appears to have been confirmed, at least in one case. Hopefully this
      observation will lead to further studies, and perhaps, new directions for
      therapy.

PMID- 24578928
TI  - A fusional anomaly of the epididymis associated with recurrent testicular
      torsion.
AB  - A 31-year-old man with recurrent testicular torsion and infertility was found to
      have a fusional anomaly of the epididymis on scrotal exploration in which only
      the head of epididymis was attached to the testis, while the body and tail were
      completely free. He had bilateral orchidopexy, which relieved pain and recurrent
      torsion. He was then referred for fertility treatment. Literature search has
      shown that infertility is more associated with congenital anomalies of the
      epididymis and not with recurrent torsions. 

PMID- 24578929
TI  - Incidentally detected emphysematous pyelonephritis.
AB  - Emphysematous pyelonephritis (EP) is a rare, severe gas forming infection of
      renal parenchyma and its surrounding areas and potentially life threatening
      condition that requires prompt evaluation and treatment. Although it commonly
      present with a fulminant clinical picture of sepsis, relatively mild symptoms can
      also be encountered. To our knowledge, incidentally detected emphysematous
      pyelonephritis has not been reported so far. We report a case of EP that was
      incidentally detected during evaluation for diabetes. 

PMID- 24578930
TI  - Serum C-reactive protein level is a significant prognostic indicator in patients
      with advanced urothelial cancer treated with gemcitabine-cisplatin or carboplatin
      - preliminary results.
AB  - INTRODUCTION: This study determines prognostic factors in patients with advanced
      urothelial cancer (UC) treated with gemcitabine-cisplatin or carboplatin (GC).
      MATERIAL AND METHODS: The clinical records of 30 patients with advanced UC
      treated with GC were retrospectively reviewed. Twenty-six patients (86.7%) had
      previously undergone other chemotherapies. Hematological parameters such as:
      neutrophil, lymphocyte and platelet counts; hemoglobin, C-reactive protein (CRP),
      and albumin levels; pain score; primary tumor site; tumor grade; type of platinum
      anti-cancer drug; and performance status before treatment were evaluated.
      Survival rates were calculated using the Kaplan-Meier method and analyzed using
      the log-rank test. Multivariate analysis was performed using a Cox proportional
      hazards model. RESULTS: The median cancer-specific survival (CSS) was 12.5
      months. The overall response rate (ORR) was 30.0%. The survival rates of patients
      with low serum albumin (<3.5 g/dL; P = 0.008), low hemoglobin (<10.1 mg/dL; P =
      0.025), high CRP (>1.0 mg/dL; P = 0.001), and a positive pain score (P = 0.002)
      were significantly worse than those with better blood values and pain scores.
      Multivariate analysis revealed serum CRP level as an independent prognostic
      indicator with a hazard ratio of 4.608 (95% confidence interval (CI) of 1.763
      12.047; P = 0.002). CONCLUSIONS: Pretreatment serum CRP levels could be an
      accurate biomarker of the survival of patients with advanced UC before GC
      therapy. Although this is a preliminary study with a small sample size, these
      results seem to be very useful in clinical practice and our findings should be
      confirmed in a larger group of patients.

PMID- 24578931
TI  - Over 500 obturator nerve blocks in the lithotomy position during transurethral
      resection of bladder tumor.
AB  - INTRODUCTION AND AIM OF THE STUDY: Spinal anesthesia for transurethral resection
      of bladder tumor (TURB) does not prevent unintended stimulation of the obturator
      nerve when electroresection is performed on the lateral wall of the bladder. It
      results in muscle contraction of the adductor muscles of the thigh, which may
      lead to perforation of bladder wall with the resectoscope loop. The aim of the
      study was to assess the efficacy and safety of obturator nerve block (ONB).
      METHODS: This prospective study was conducted between 01/01/1999 and 12/31/2010
      in the Department of General, Oncologic and Functional Urology, Medical
      University of Warsaw. In 431 patients undergoing TURB adductor spasms were
      observed. In these cases nerve stimulation and ONB with 2% lidocaine using thigh
      interadductor approach in the lithotomy position were performed. RESULTS: The
      efficacy of 542 ONB was 94%. In 31 cases general anesthesia was necessary. There
      were two cases of urinary bladder perforation, but only one resulted from an
      insufficient nerve block. Both were managed conservatively. Neither hematomas nor
      neurological adverse events were observed. CONCLUSION: The described method
      offers a high rate of efficacy and ensures optimal and safe conditions for the
      resection of a tumor located on the inferolateral wall of the urinary bladder.
      The risk of complication is low.

PMID- 24578932
TI  - Laparoscopic adrenalectomy - ten-year experience.
AB  - OBJECTIVES: The objective of the study is to summarize the authors' 10-year
      experience with laparoscopic adrenalectomy and to analyze the intra- and
      postoperative complications of the procedure. MATERIAL AND METHODS: The records
      of 80 patients who had undergone laparoscopic adrenalectomy from January 2002 to
      January 2012 were reviewed retrospectively. There were 51 female and 29 male
      patients. The average age was 52. In 33 cases the right adrenal gland was
      affected, in 47 it was the left adrenal gland. Nineteen operations were performed
      with the retroperitoneal approach, in 61 a transperitoneal access was used. The
      average size of the tumor was 5 cm. The diagnosis was based on ultrasonography
      (USG) and computed tomography (CT). The biochemical tests were performed in all
      cases to assess hormonal activity of the tumor. Pheochromocytoma was diagnosed in
      16 cases, Cushing syndrome in 3 cases, and Conn syndrome in 4 cases. All other
      tumors were hormonally inactive. Six patients were operated on because of adrenal
      metastases - from renal carcinoma in five cases and from lung carcinoma in one
      case. RESULTS: There were three open conversions. The mean operative time was 158
      minutes. The mean hospital stay was 5.5 days Blood transfusion was necessary in
      three patients. Postoperative complications were observed in 11 patients (13.7%).
      CONCLUSIONS: Laparoscopic adrenalectomy is a safe and effective procedure and
      should be considered the first - line treatment of benign adrenal masses. Our
      experience indicates that patients with adrenal metastases are suitable
      candidates for laparoscopic adrenalectomy, providing a skilled laparoscopic
      surgeon is involved in operation.

PMID- 24578933
TI  - Complete laparoscopic nephroureterectomy with intravesical lockable clip.
AB  - INTRODUCTION: We present a cohort of patients with low-stage pelviureteric
      neoplastic disease who underwent complete laparoscopic nephroureterectomy (CLNUE)
      with intravesical lockable clip (IVLC). Due to the absence of a standard
      technique of NUE, the study was not randomized. MATERIALS: From 1/2010 to 1/2012,
      21 patients were subjected to CLNUE-IVLC. The first step was transurethral
      excision of the ureterovesical junction with Collin's knife deep into the
      paravesical adipose tissue. The ureter was grasped with biopsy forceps and the
      distal end of the ureter was occluded with lockable clip. The applicator was
      introduced through a 5 mm port inserted as an epicystostomy. The patients were
      rotated to flank position and CLNUE followed. The endoscopically introduced clip
      on the distal ureter is proof of completion of the total ureterectomy. RESULTS:
      The mean operation time was 161 (115-200) min. In four (19.0%), the application
      of the clip failed and CLNUE was completed with non-occluded ureter. In three
      cases, subsequent laparoscopic nephrectomy was converted to open surgery. In two
      cases, the distal ureterectomy was completed with pluck technique through a lower
      abdominal incision that was also used for extraction of the specimen. There were
      four complications (Clavien II 2x, IIIb, V). Follow-up was available for all -
      mean 10.6 (range: 0-25) months. One died of disease generalization within 11
      months. CONCLUSION: CLNUE-IVLC is fast and safe. If needed, the endoscopic phase
      can be switched to open NUE. Disadvantages include: the need to change the
      position of the patient, the risk of inability to apply the clip on the distal
      ureter, and the risk of an unclosed defect of the urinary bladder.

PMID- 24578934
TI  - Selected examples of complications after minimally invasive treatment for
      urolithiasis.
AB  - In recent years urologists have concentrated on the intense introduction of
      minimally invasive methods for the treatment of urinary tract diseases with major
      progress noted in the treatment of urolithiasis. Nowadays extracorporeal
      shockwave lithotripsy (ESWL), percutaneous nephrolithotomy (PCNL), and
      ureteroscopic lithotripsy (URSL) are widely used in the treatment of urinary
      tract lithiasis. The aim of this study is to present examples of urinary tract
      lithiasis as the complication after minimally invasive methods used in the
      treatment of urolithiasis. One should remember that even minimally invasive
      medical procedures using the instruments retained in long-term contact with urine
      may be the cause of incrustation and stone formation. 

PMID- 24578935
TI  - Polymorphic variants of H-RAS protooncogene and their possible role in bladder
      cancer etiology.
AB  - INTRODUCTION: H-RAS gene is a protooncogene encoding p21ras, a small protein with
      GTPase activity. This protein is a component of many signaling cascades, while
      mutations in H-RAS gene are often found in urinary bladder cancer and leads to
      continuous transmission of signals stimulating cancer cell growth and
      proliferation. The T81C polymorphism of H-RAS gene is a SNP, which, although does
      not seem to impair p21ras protein structure and function, may contribute to the
      development of bladder cancer. OBJECTIVES: The aim of our study was to
      characterize the prevalence and clinical significance of T81C polymorphism in
      patients with diagnosed bladder cancer. MATERIALS AND METHODS: 132 patients with
      diagnosed urinary bladder cancer were included in this study. The control group
      consisted of 106 healthy individuals. The experimental material was DNA, isolated
      from tumor tissue and peripheral blood lymphocytes. T81C polymorphism was
      detected using the MSSCP method and DNA sequencing. RESULTS: In the examined DNA
      samples, frequent polymorphic variations were found in codon 27 of H-RAS gene. In
      order to assess the clinical relevance of the polymorphism, the results were
      compared with those for the control group. The homozygous CC variant occurred
      more frequently in bladder cancer patients than in healthy individuals.
      CONCLUSIONS: DNA polymorphisms start to play an important role in evaluation of
      disease risk and progression. The occurrence of multiple variants of the same
      gene may contribute to differences in reactions to specific medications and
      sensitivity to carcinogens or DNA repair capacity. Our study demonstrated T81C
      polymorphism of H-RAS gene to have seemingly been associated with an increased
      risk of bladder cancer development.

PMID- 24578936
TI  - Management of encrusted ureteric stent and impacted stone in pregnancy - a
      challenging dilemma.
AB  - We are presenting an interesting case of impacted stone and stent in a pregnant
      patient. We have proved safe use of ureteroscopy and laser in pregnancy with
      minimal x-ray exposure. 

PMID- 24578937
TI  - Urethral duplication: a rare cause of urinary incontinence in a female child.
AB  - Female urethral duplication is a rare congenital anomaly. We report a case of
      complete urethral duplication along with horseshoe kidney in a four-years-old
      female child presenting with incontinence since childhood. 

PMID- 24578938
TI  - A case of Fournier's gangrene after hydrocelectomy.
AB  - An uncommon case of Fournier's gangrene following hydrocelectomy is described. A
      78-year-old male with no remarkable previous history, who underwent
      hydrocelectomy in another hospital, developed Fournier's gangrene 15 days later.
      The patient required wide aggressive surgical debridement, hyperbaric oxygen
      chamber and broad-spectrum antibiotic coverage. Afterwards the patient was
      referred for plastic surgery. Fournier's gangrene is a polymicrobial infection of
      perineoscrotal region that manifests as a rapidly progressive necrotizing
      fasciitis. Fournier's gangrene following hydrocelectomy is uncommon. The
      morbidity and mortality in this severe complication depend on early diagnosis and
      aggressive surgical management. 

PMID- 24578939
TI  - A case of descending colon carcinoma metastasized to left spermatic cord, testis,
      and epididymis.
AB  - We report a case of descending colon carcinoma metastasized to the left spermatic
      cord, testis, and epididymis. A 77-year old male patient underwent a left
      hemicolectomy for a descending colon cancer. He was referred to our department
      because of swelling and pain of the left scrotum two years and six months after
      surgery. High left orchiectomy was performed. Histological examination revealed a
      metastasis of the colon carcinoma within the spermatic cord and epididymis
      approaching the testicle. Reports on metastatic cancer of the testis are scarce,
      because this metastatic cancer is extremely rare. In general, testicular pain is
      rare in the elderly. We suggest that any elder presenting with testicular pain
      deserves a complete clinical and diagnostic evaluation. 

PMID- 24578940
TI  - A case of metastatic prostate adenocarcinoma to an inguinal lymph node.
AB  - A 47-year-old man presented with dysuria. The prostate-specific antigen level was
      65.5 ng/mL. Retropubic radical prostatectomy and regional lymphadenectomy
      revealed moderately differentiated adenocarcinoma (Gleason score 3 + 4 = 7,
      pT2N0). Postoperative adjuvant hormonal therapy was started immediately. Three
      years later, hormonal therapy was changed to anti-androgen monotherapy.
      Monotherapy was continued for eight years and then discontinued because the PSA
      level was maintained at <0.04 ng/mL. However, biochemical recurrence occurred 12
      months after adjuvant hormonal therapy was discontinued. A computed tomography
      scan showed left inguinal lymphadenopathy. Biopsy of the swollen inguinal lymph
      node revealed metastatic prostate cancer. We report a rare case of metastatic
      prostate adenocarcinoma only to the inguinal lymph nodes. 

PMID- 24578941
TI  - Pseudosarcomatous fibromyxoid tumor of the prostate revealed on suprapubic
      prostatectomy.
AB  - We report a rare case of inflammatory pseudotumor of the prostate revealed on
      suprapubic prostatectomy. A 70-year-old man presented with nocturia, urgency and
      difficulty in voiding. The histopathological examination of the suprapubic
      adenomectomy specimen reported fibromyxoid pseudosarcomatous tumor (inflammatory
      prostatic pseudotumor). It is important to take this benign lesion under
      consideration to avoid unnecessary aggressive radical complementary treatments. 

PMID- 24578942
TI  - Laparoscopic radical nephrectomy in extremely obese patients.
AB  - Laparoscopic radical nephrectomy has been widely accepted as the preferred
      management of low stage renal masses. Endoscopic management is advantageous for
      its reduction in perioperative and postoperative complications. In the mid-1990s,
      morbid obesity was considered a relative contraindication to laparoscopic
      technique. The authors present two cases of laparoscopic radical nephrectomy due
      to renal tumors in extremely obese patients. The aim of this study is not only to
      present the operative technique but also to show that the laparoscopic procedure
      is safe and effective in morbidly obese patients. 

PMID- 24578943
TI  - How accurate is our prediction of biopsy outcome? PCA3-based nomograms in
      personalized diagnosis of prostate cancer.
AB  - PURPOSE: The sensitivity and specificity of prostate-specific antigen (PSA) alone
      to select men for prostate biopsy remain suboptimal. This review aims at
      presenting a review of current prostate cancer (PCa) nomograms that incorporate
      Prostate Cancer Gene 3 (PCA3), which was designed to outperform PSA at predicting
      biopsy outcome. MATERIALS AND METHODS: The PubMed database and current literature
      search was conducted for reports on PCA3-based nomograms and tools for examining
      the risk of a positive prostate biopsy in a man without a known PCa diagnosis.
      RESULTS AND CONCLUSIONS: The introduction of PCA3 into clinical practice has led
      to the development of a set of PCA3-based nomograms to predict biopsy outcome.
      Combining PCA3 results with established PCa risk factors has produced significant
      improvements over PSA alone in predicting the risk of a positive prostate biopsy
      for cancer.

PMID- 24578944
TI  - Samuel Goldflam (1852-1932) - promoter of modern neurology and his contribution
      to urology.
AB  - The work of Samuel Goldflam is well known among urologists and nephrologists but
      his name also holds a special significance to the development of several
      specialist disciplines of modern medicine. A shaking symptom of the lumbar region
      (Goldflam's sign) described in 1900 is relevant to both urologic and internal
      medicines. The key importance of Goldflam's sign in the diagnosis of renal and
      urinary tract diseases emphasizes the outstanding contribution of this Polish
      researcher to the development of medicine. The aim of this study is to briefly
      present the rich curriculum vitae and achievements of Samuel Goldflam, the Polish
      neurologist who changed urology and internal medicine on a worldwide scale. "Our
      endeavor is to obtain as many grounds as possible on which to facilitate the
      recognition of early periods of a disease. This is of great therapeutic
      importance". (Samuel Goldflam). 

PMID- 24578945
TI  - Complication rates after prostate biopsy according to the number of sampled
      cores.
AB  - INTRODUCTION: A PROSTATE BIOPSY CAN RESULT IN SUCH COMPLICATIONS AS: hematuria,
      rectal bleeding, pain in hypogastrium, perineum or urethra, fever, nausea,
      vomiting, retention of urine or other adverse events. The aim of this research
      was to estimate complication rates after a prostate biopsy based on the number of
      cores. MATERIAL AND METHODS: The complication rate was evaluated on the basis of
      questionnaires filled out by patients. Questions were related to the occurrence
      of mentioned complications on the first and second day after prostate biopsy.
      Patients were divided into two groups: 1(st) group (41 patients) 5-8 cores and
      2(nd) group (73 patients) 12 or more cores. RESULTS: There was no significant
      statistical difference in the occurrence of complications mentioned in the
      questionnaires in both groups. The biggest difference was recorded for hematuria 
      1(st) day: 39% in the 1st and 53% in the 2nd group (p = 0.1398); 2(nd) day: 15%
      in the 1(st) and 30% in the 2(nd) group (p = 0.0650). Rectal bleeding on the
      1(st) day also seems to vary: 12% in the 1st and 26% in the 2(nd) group (p =
      0.0835). Other complications occurred in 3-8% of patients. 32% of patients in the
      1(st) and 29% in the 2(nd) group (p = 0.7419) had no complications at all.
      CONCLUSIONS: The most common complications after a prostate biopsy are hematuria
      and rectal bleeding. Other complication rates are low. In general, complication
      rates after a prostate biopsy procedure are not related to the number of sampled
      cores.

PMID- 24578946
TI  - beta-catenin as a prognostic factor for prostate cancer (PCa).
AB  - INTRODUCTION: The prostate cancer is difficult to predict, and treatment failure
      is associated with local infiltration, as well as distant metastases. Adhesion
      and migration abilities to of cancer cells play a major role in formation of
      metastasis. The participation of beta-catenin in pathogene-sis of many types of
      cancer and benign processes has been an important discovery of recent years.
      MATERIAL AND METHODS: The studied material was obtained by transrectal, sextant
      core biopsy from 102 patients hospitalized in Department of Urology, Regional
      Hospital in Kalisz (2001-2004). The aim of our study was to determine the
      predictive value of beta-catenin immunoexpression in prostate cancer, to analyze
      the prognostic aspect of some histopathological features and finally to assess
      the relationship between beta-catenin immunoreactivity and the microscopic image
      of the tumor. Relationships between the investigated variables were analyzed
      using the Chi(2) test of compatibility. We used the Kaplan-Meier curves to assess
      survival differences between groups of patients. Finally we established which of
      the studied factors significantly affect the patient outcome, using the method of
      Cox proportional hazard regression. RESULTS: In prostate cancer in comparison
      with the normal epithelium, both the location and the strength of beta-catenin
      immunoexpression are impaired. CONCLUSIONS: Our results indicate that the
      presence of disorders in beta-catenin immunoexpression in prostate cancer cells
      indicates a high risk of death due to tumor progression and makes it imperative
      for immediate treatment procedures.

PMID- 24578947
TI  - A single institution study on patient's self-reporting appraisal and functional
      outcomes of the first set of men following radical perineal prostatectomy.
AB  - INTRODUCTION: This study evaluates the functional outcomes and satisfaction of an
      initial series of 47 patients after radical perineal prostatectomy performed in
      our department. MATERIAL AND METHODS: The first set of 47 consecutive patients
      underwent perineal prostatectomy during 2008 and 2009. Continence, sexual
      outcomes, and satisfaction of the treatment were evaluated using a self-reporting
      questionnaire, which was mailed to all patients after 15 to 33 months of follow
      up. 26 patients (55.3%) returned a completed form and participated in the study.
      Additionally, final outcomes were compared to results reported elsewhere.
      RESULTS: Amid respondents, 91.7% were satisfied with the chosen treatment and
      8.3% regret the previous decision. 38.5% patients reported any urine leakage,
      15.4% drip up to 100 ml a day, and only one patient (3.8%) was totally
      incontinent. 76.9% men report a decline in prior sexual function. Six patients
      (23.1%) patients have any degree of spontaneous erections and undertake sexual
      activity. However, as erectile outcomes are adjusted to nine nerve-sparing cases,
      66.7% have spontaneous erections and 55.5% undertake sexual activity, but only
      40% of them describe their sexual function as satisfying. CONCLUSIONS: Our survey
      demonstrates that, because of short operating time, fast recovery, low
      postoperative pain score, early patient mobilization and feeding, and a small (8
      10 cm) and inconspicuous skin incision, radical perineal prostatectomy fully
      deserves to be recognized as a low-morbidity procedure. The perineal approach
      provides a quality of life and patients satisfaction rate comparable to trendy,
      highly equipped procedures and emerges as an attractive alternative to them. Even
      novice "perineal surgeons" may achieve favorable results.

PMID- 24578948
TI  - Thulium laser enucleation of the prostate (TmLEP) vs. transurethral resection of
      the prostate (TURP): evaluation of early results.
AB  - INTRODUCTION: The first decade of XXI century it is a time of the thulium laser
      implementation to a benign prostatic hyperplasia treatment. OBJECTIVE: The
      objective of this paper is a comparative assessment of early results thulium
      laser enucleation of the prostate (TmLEP) versus transurethral resection of the
      prostate (TURP) in 3-months observation. MATERIALS AND METHODS: PATIENTS WERE
      RANDOMIZED TO BPH SURGICAL TREATMENT: research group (TmLEP - 54 men) or control
      group (TURP - 52 men). Between 02.2007-09.2009 non-consecutive patients were
      examined before, one month, and 3-months after surgery. Perioperative data (age,
      PV, time of surgery, use of laser, morcellation, catheterization,
      hospitalization, used energy, Hgb loss and removed tissue weight) were assessed.
      Before and after surgery IPSS, QoL, Qmax and PVR were controlled. RESULTS:
      Hemoglobin loss was twice lower during TmLEP than TURP [0.95 +/-0.77 (0-3.2) vs.
      1.81 +/-0.97 (0.1-4.7) g/dl, p <0.0001]. Surgery time TmLEP was longer than TURP
      [102.2 +/-38.7 (25-210) vs. 74.5 +/-22.8 (25-140) min. p <0.0001]. Without
      morcellation time [28.1 +/-17.9 (5-80) min.], surgery time of both procedures was
      comparable. Weight of resected tissue was lower in TmLEP than TURP [24.8 +/-14.8
      (2-65) vs. 34.8 +/-14.1 (12-68)g]. without consideration of vaporized tissue. In
      both groups we noticed a distinct improvement in all parameters: IPSS, QoL, Qmax
      and PVR, but without any statistically significant differences between them.
      Complications after surgery were similar in TmLEP and TURP group. CONCLUSIONS:
      The thulium laser enucleation of the prostate is safe and efficient BPH treatment
      method, comparable to the transurethral electroresection in 3-months observation.
      Lack of long-term research does not allow to form wider conclusions.

PMID- 24578949
TI  - Assessing the Influence of Benign Prostatic Hyperplasia (BPH) on Erectile
      Dysfunction (ED) among patients in Poland.
AB  - INTRODUCTION: Erectile dysfunction (ED) and the lower urinary tract symptoms
      caused by benign prostatic hyperplasia (LUTS/BPH) are highly prevalent among
      aging men. More data are needed from studies evaluating the impact of LUTS/BPH on
      ED. This study aimed to assess ED in patients with LUTS/BPH independent of
      comorbidities. MATERIAL AND METHODS: During 2007 and 2008, we examined 10,932
      patients aged 50 to 69 years with LUTS/BPH (IPSS = 8-19 points) using
      questionnaires: Sex-Score and International Index of Erectile Function 5 (IIEF
      5). Patients who used alcohol and/or cigarettes and those with hypertension,
      diabetes, or hyperlipidemia and cholesterolemia were excluded from meta analyses,
      which left 4,354 patients with LUTS/BPH without any comorbidity for the analyses.
      The main survey instruments used were the Sex-Score and IIEF-5. RESULTS:
      Regarding sexual coexistence, 1,497 (34.4%) and 2,638 (60.6%) patients considered
      it very important or important respectively; however, 219(5%) patients reported
      no sexual activity. After excluding sexually inactive patients, only 1,088 (25%)
      patients had the ability to obtain an erection during sexual activity always or
      nearly always. However, that erection was only strong enough to penetrate their
      partner almost always or most of the time in 218 (5%) and 826 (19%) patients
      respectively and only 610 (14%) patients were always able to maintain their
      erection during sexual intercourse. While only 87 (2%) patients had no difficulty
      maintaining their erection until the completion of intercourse, 174 (4%) and 914
      (21%) patients stated that sexual intercourse gave satisfaction nearly always or
      most of the time respectively. CONCLUSIONS: The impact of ED on patients with
      LUTS/BPH is evident across domains.

PMID- 24578950
TI  - Acute epididymo-orchitis: staging and treatment.
AB  - INTRODUCTION: Acute epididymo-orchitis (AEO) is an acute inflammatory disease of
      the epididymis and ipsilateral testis. Treatment should be started immediately
      after diagnosis and includes antibiotics, analgesics, and, if necessary, surgery.
      MATERIALS AND METHODS: After AEO diagnosis, patients were treated conservatively
      with analgesics and antibiotics. If no clinical improvement was observed within
      the first 48-72 hours of conservative treatment, patients underwent surgery.
      Depending on examination results, 254 patients (pts.) were divided into three
      groups: 1) with palpable differences between the epididymis and testis (E/T+),
      and without neither hydrocele, local softening (malacia), nor abscess of the
      epididymis or testis; 2) with E/T+, absence of malacia, presence of hydrocele,
      and none, one, or a few small abscesses within the epididymis/testis and 3)
      without palpatory differentiation between the epididymis and testis, with or
      without malacia, with hydrocele, and none, one, or more abscesses of any size. We
      analyzed the clinical outcomes in each group. RESULTS: All of patients from the
      first group were successfully treated with antibiotics. In the second group,
      conservative treatment was effective in 70 pts. (85.4% of this group), but the
      other 12 pts. (14.6%) did not show clinical improvement and underwent organ
      sparing surgery. The majority of patients from the third group did not
      demonstrate an objective response to antibacterial treatment during the first 48
      72 hours and, therefore, underwent surgery. Based on examination results and
      clinical outcomes we developed a classification system for AEO, which divides AEO
      into three stages and recommends an approach to its treatment. CONCLUSIONS: Our
      classification is able to systematize treatment approaches in patients with AEO.

PMID- 24578951
TI  - Fertility preservation in cases of laparoscopic treatment of seminal vesicle
      cysts.
AB  - Seminal vesicle cysts can cause sub- or infertility. Minimally invasive
      techniques have the advantage of preserving the vas deferens by the treatment of
      symptomatic cases. After reviewing the published articles, only a few of them
      presented data on fertility before and after surgery. The authors now report the
      successful treatment of two patients with seminal vesicle cysts, in which
      laparoscopic cyst removal resolved the symptoms, preserving fertility and
      erectile function. Due to the rarity of seminal vesicle cysts, preoperative
      examinations and treatment modalities should focus not only on the relief of
      symptoms but also on the preservation of fertility and erectile function. 

PMID- 24578952
TI  - HIF-1, GLUT1, endoglin, and BIRC5 expression in urine samples obtained from
      patients with bladder malignancies - after photodynamic diagnosis (PDD).
AB  - INTRODUCTION: Bladder cancer (BC) is a serious medical problem. The high rate of
      recurrence and progression demands the development of new methods, such as
      genetic markers, which allow diagnosis and patient follow-up. OBJECTIVES: The aim
      of this study was to compare expression of HIF-1, GLUT1, endoglin, and BRIC5 in
      patients without and those with BC. The second group was divided into sub-groups:
      those without a history of PDD (photodynamic diagnosis) in the diagnostic process
      and those after PDD. METHODS: Patients with BC were diagnosed using the PDD
      method using hexaminolevulinate (Hexvix((r))). The expressions of HIF-1, GLUT1,
      endoglin, and BRIC5 genes were established in urine specimens by real-time
      quantitative polymerase chain reaction (PCR). RESULTS: The expressions of all
      tested genes were higher in the group of patients with BC than in the group
      without BC. In the group after PDD, a statistically significant overexpression of
      HIF-1 was observed. In this group, changes were not observed in cases of the
      other three tested genes. CONCLUSIONS: The differences between the group with PDD
      and the group without it can be connected with the direct influence of PDD on
      malignant tissue, which can cause overexpression of HIF-1 only. This is, however,
      only a hypothesis and needs further study.

PMID- 24578953
TI  - Therapeutic results in stage I Wilms' tumors in children - 15 years of surgical
      experience.
AB  - INTRODUCTION: Progress in the therapeutic management of Wilms' tumors (WT) in
      children has resulted in the fact that presently, almost all children with stage
      I and favorable histology diseases have a chance for a cure. THE AIM OF THE
      STUDY: The objective of the report is an analysis of therapeutic results in
      children with unilateral stage I Wilms' tumors depending on the extent of tumor
      resection. MATERIAL AND METHODS: The analysis included children treated between
      1993 and 2008 under the Polish Wilms' Tumor Study, initially following the
      protocol SIOP 93-01 (patients treated up to 2002) and subsequently SIOP 2001.
      Following neoadjuvant chemotherapy, depending on tumor size and tumor response to
      treatment, the children were qualified for a radical nephrectomy, simple
      nephrectomy, or nephron-sparing surgery. Following surgical treatment, all the
      children were subjected to adjuvant chemotherapy in keeping with the therapeutic
      protocol obligatory at the time. RESULTS: Within the 15 years, 111 children with
      Wilms' tumor were treated; the group included 43 children with stage I disease,
      which constituted 38.9% of the total number. Radical nephrectomies were performed
      in three (6.98%) children, simple nephrectomies in 32 (74.42%), and nephron
      sparing surgery in eight (18.6%). Regardless of the employed surgical treatment
      modality, all the children are alive and none have demonstrated recurrent
      disease. The mean post-treatment completion follow-up period is 73 months (median
      value, 68 months). CONCLUSION: A simple nephrectomy and, whenever possible,
      nephron-sparing surgery represents sufficient treatment in 93% of children with
      stage I Wilms' tumor. To improve qualification for surgical treatment we propose
      the employment of NSS for stage Ia Wilms' tumors and SN for stage Ib Wilms'
      tumors.

PMID- 24578955
TI  - Pyelonephritis xanthogranulomatosa in a 7-year-old girl.
AB  - Xanthogranulomatous pyelonephritis (XGPN) is rare form of chronic, usually
      unilateral, renal infection that involves damage to the renal glomeruli and
      periglomerular tissue and destruction of the renal parenchyma. Nephrectomy is
      usually necessary and the prognosis is good if XGPN is unilateral and treated
      early. XGPN typically affects middle-aged females and is extremely rare in
      children. We report one case of XGPN in a seven-year-old girl who was operated on
      at our institution be-cause of lower urinary tract dysfunction and renal
      insufficiency - the left kidney was removed and the bladder was augmented by
      means of the remaining ureter. The histopathological evaluation of the removed
      kidney showed chronic XGPN. 

PMID- 24578954
TI  - Long-term follow-up after botulinum toxin A (BTX-A) injection into the detrusor
      for treatment of neurogenic detrusor hyperactivity in children.
AB  - PURPOSE: To prove the long-term efficacy of BTX-A injection in the management of
      children with neurogenic detrusor hyperactivity. MATERIALS AND METHODS: 28 out of
      145 children with neurogenic bladder (15 male and 13 female, mean age 10.7 years)
      who were treated between 2002 and 2010 and became non-responders to conservative
      treatment were included into the retrospective study. We injected 10-12 U/kg of
      BTX-A (Botox((r))) into the detrusor at 20-30 sites, sparing the trigone. The
      mean follow-up was 48 months (range 6-84 months). RESULTS: Group 1. 14 patients
      had a single injection of BTX-A. Five of them were successful. Mean bladder
      reflex volume increased (from 62.9 to 117.5 ml), maximum detrusor pressure
      decreased (from 59 to 37.5 cm H2O), detrusor compliance increased (from 4.8 to
      9.5 ml/cm H2O), and leak-point-pressure decreased (from 46.5 to 24.2 cm H2O).
      Four patients did not respond and were treated by ileocystoplasty. Another five
      were lost to follow-up. Group 2. 14 patients had repeated (mean 2.5) injections
      of BTX-A with a mean interval of 13.7 months. In thirteen patients, urodynamic
      parameters of the first and last injection were similar to those obtained in
      Group 1, showing a good response. One patient received an ileocystoplasty.
      CONCLUSION: BTX-A is a safe alternative in the treatment of detrusor
      hyperactivity in children with myelomeningocele (MMC). The efficacy lasted a mean
      of 12 months and urodynamic response was unchanged even after several injections.
      In our series, 21.7% of children with severe low-compliance bladders were non
      responders.

PMID- 24578956
TI  - Mucinous tubular and spindle cell carcinoma.
AB  - A case of a 30-year-old female patient diagnosed with mucinous tubular and
      spindle cell carcinoma (MT&SCC) of her left kidney of the basis of an abdominal
      ultrasound scan performed when nonspecific pain is presented. The histopathology
      report revealed a classic type of MT&SCC. Photographs of histopathological
      samples are shown. Nephrectomy was applied as sole treatment. A follow-up of six
      years confirmed surgery to be a sufficient approach. The discussion presents a
      review of up to date world literature concerning the histopathological features,
      prognosis, and treatment of MT&SCC. 

PMID- 24578957
TI  - Acne inversa of the scrotum and penis - aggressive urological treatment.
AB  - Acne inversa is a rare chronic and debilitating inflammatory skin disease. The
      authors report a case of a 45-year old male who presented with acne inversa in
      the inguinal, perineal, and scrotal areas. After unsatisfactory pharmacological
      treatment a wide surgical excision of the affected skin was performed in stages.
      On follow-up the patient presented with a very good cosmetic and functional
      result. A review of the most recent literature is also presented. 

PMID- 24578958
TI  - Milk of calcium (MOC) cysts masquerading as renal calculi - a trap for the
      unwary.
AB  - Milk of calcium (MOC) is a colloidal suspension of calcium salts occurring in
      calyceal cysts and diverticula. Although reported to be rare, in fact it seems to
      be more common than previously thought. It has characteristic appearances on
      plain x-rays, ultrasound, and CT imaging particularly in the prone and supine
      positions. Often entirely asymptomatic, its appearance may be mistaken for renal
      stones on radiography or angiomyolipomas on ultrasonography. In this paper, a
      series of cases is presented outlining its characteristic features and reviewing
      the relevant literature. 

PMID- 24578959
TI  - Genitourinary tuberculosis: historical and basic science review: past and
      present.
AB  - Genitourinary tuberculosis (GUTB) usually results from the reactivation of old,
      dormant tuberculous diseases by pathogens of the mycobacterium tuberculosis
      complex. GUTB is the second most common form of extrapulmonary tuberculosis, with
      more than 90% of cases occurring in developing countries. In GUTB, the kidneys
      are the most common sites of infection and are infected through hematogenous
      spread of the bacilli, which then spread through the renal and urinary tract.
      Patients with genital and urethral TB present with a superficial tuberculous
      ulcer on the penis or in the female genital tract develop mainly due to primary
      contact with mycobacterium exposure during intercourse or inoculation via goods
      or chattels contaminated with mycobacterium. The diagnosis of TB of the urinary
      tract is based on the case history, the finding of pyuria in the absence of
      infection as judged by culture on routine media, and by radiological imaging.
      However, a positive yellow egg culture and/or histological analysis of biopsy
      specimens, possibly combined with the polymerase chain reaction (PCR), is still
      required in most patients to establish a definitive diagnosis of GUTB. The
      standard antituberculous drug treatment should be administered initially for two
      months during the intensive phase with three or four drugs daily followed by dual
      continuation therapy for four months. Surgery as a treatment option in GUTB might
      be indicated in complicated urinary tuberculosis. After antituberculous treatment
      of GUTB, surveillance with regular follow-up visits over the next five years is
      recommended. In cases of drug resistance, additional drugs and prolonged
      treatment are required. Furthermore, increasing rates of drug-resistant cases and
      co-infection with HIV pose challenges in the treatment GUTB and other forms of
      TB. 

PMID- 24578960
TI  - Radical perineal prostatectomy - the contemporary resurgence of a genuinely
      minimally invasive procedure: Procedure outline. Comparison of the advantages,
      disadvantages, and outcomes of different surgical techniques of treating organ
      confined prostate cancer (PCa). A literature review with special focus on
      perineal prostatectomy.
AB  - INTRODUCTION: Surgery plays a central role in the management of organ-confined
      prostate cancer (PCa). Four types of prostatectomy are currently practiced:
      perineal, retropubic, laparoscopic, and robot-assisted. The qualification
      criteria for all types are similar. Radical perineal prostatectomy (RPP) was the
      first method introduced into clinical practice, however, it has been neglected in
      favor of other procedures. Its resurgence has been facilitated by a multitude of
      advantages. Unfortunately, nowadays most urologists are not familiar with the
      perineal approach though many centers have begun to implement it. MATERIALS AND
      METHODS: This manuscript presents the technique of RPP used in the author's
      institution. It also reviews a vast body of literature on the four techniques of
      prostatectomy including their advantages and outcomes. The data was collected
      from the literature and medical databases. CONCLUSION: RPP proves to be a very
      efficacious, cost-effective treatment option for localized PCa. The outcomes of
      RPP, as defined by continence, potency, and complication rate, are equivalent to
      those accomplished by other methods.

PMID- 24578961
TI  - Clinical significance of surgical margin status in patients subjected to radical
      prostatectomy.
AB  - The aim of this study is to evaluate the clinical value of positive surgical
      margins (PSM) in patients subjected to radical prostatectomy (RP). The data of
      men who were subjected to RP from the 1st of January, 2001 to the 30th of May,
      2010 were analyzed. Specimens with PSM were again evaluated to confirm the
      presence of positive margins. PSM were found in 64 (25%) out of 255 analyzed
      patients. Out of all clinical features, only biopsy Gleason score and clinical
      stage of the disease were found to be predictive of PSM. Biochemical recurrence
      (BR) was found in 42 (16.5%) men, among them 17 (26.6%) had PSM and 25 (13.1%)
      had negative margins. The risk of BR in those with "focal" PSM (<3 mm) did not
      differ from the risk of BR observed in patients without PSM. In contrast, the
      likelihood of BR was significantly greater in cases of PSM in which maximum
      longitude exceeded 3 mm. Reevaluation of the PSM specimens revealed equivocal
      margins status in six cases. PSM are not inevitably associated with BR. The risk
      of failure is influenced by their length. Reevaluation of the prostate specimen
      may lead to surgical margins status modification. 

PMID- 24578962
TI  - Hyperbaric oxygen therapy (HBOT) in case of hemorrhagic cystitis after
      radiotherapy.
AB  - INTRODUCTION: We present the effect of hyperbaric oxygen therapy (HBOT) after
      radiotherapy for cancer in the pelvic cavity resulting in hematuria. Increasing
      the pressure of oxygen (PO2) in ischemic tissues favors the formation of new
      blood vessels and increases the secretion of collagen. MATERIAL AND METHODS: We
      evaluated 10 patients who were treated with HBOT from October 2006 to December
      2010 due to persistent radiation damage to the lining of the bladder leading to
      recurrent hematuria. The study group was comprised of seven men and three women.
      In the case of cervical and endometrial cancers, 30 Gy of brachytherapy with 45
      50 Gy of teleradiotherapy were used. In prostate cancer (PCa), we applied 50 Gy
      of teleradiotherapy with an additional dose of 20-24 Gy, and in the case of
      bladder cancer (BCa), 50 Gy of teleradiotherapy was applied with an additional
      dose of 16 Gy. HBOT consisted of 60 HBO2 treatments, in which patients were
      administered 100% oxygen at a pressure of 2.5 atm. RESULTS: The group effect of
      total or partial resolution was observed in six patients. In one case, treatment
      was discontinued due to an increase in hematuria and the consequent suspicion of
      bladder tumor recurrence. While in and additional three cases, the treatment did
      not produce the desired result. CONCLUSIONS: Treatment of hemorrhagic cystitis is
      a difficult therapeutic challenge. One possible method is the implementation of
      HBOT. In very difficult cases, HBO2 treatment appears to be effective in giving
      more than half of patients a chance of getting better.

PMID- 24578963
TI  - Laparo-endoscopic single-site surgery: recent advances in urology.
AB  - Significant advances have been achieved in the field of urologic laparo
      endoscopic single-site surgery (LESS) since the first reported clinical series in
      2007. The aim of the present review paper is to summarize and critically analyze
      the most recent advances in the field of urologic LESS. A literature review was
      performed using PubMed to retrieve publications related to LESS in urology over
      the last two years (from January 2011 to May 2012). In the free-text protocol,
      the following terms were applied: LESS; single port laparoscopy; single incision
      laparoscopy. Despite unsolved challenges, LESS can be regarded as an emerging
      trend in minimally invasive urologic surgery and it has significantly evolved,
      becoming a widely applicable technique in a relatively short time. Outcomes
      demonstrate that a broad range of procedures can be effectively and safely done,
      given a solid laparoscopic surgical background and stringent patient-selection
      criteria. The recent introduction of a purpose-built instrumentation is likely to
      further foster the application of robotics to LESS. Further improvements are
      needed before this technique might reach a widespread adoption. Future advances
      in the field of robotic technology are expected to overcome the current
      limitations of LESS. 

PMID- 24578964
TI  - High efficacy of biofeedback therapy for treatment of dysfunctional voiding in
      children.
AB  - INTRODUCTION: Dysfunctional voiding is a frequent condition in children
      associated with symptoms of incontinence. The aim of this study was to present
      the efficacy of biofeedback treatment on the resolution of clinical symptoms in a
      large cohort of children with urodynamically confirmed dysfunctional voiding.
      MATERIAL AND METHODS: 81 children (75 girls and 6 boys) aged 6-18 years (mean:
      10.32 +/-3.17 yrs.) with a dysfunctional voiding pattern are presented. 74/81
      (92.6%) of children were unresponsive to standard urotherapy and prior
      pharmacotherapy. Symptoms of bladder dysfunction were evaluated by questionnaire,
      bladder diary and an urodynamic study according to definitions and standards set
      by ICCS. The biofeedback training was planned for 2 months. Each session
      consisted of about 30 repeats of 5 s contraction and 30 s relaxation of pelvic
      floor muscles and external urethral sphincter. Biofeedback was performed together
      with standard urotherapy. RESULTS: 67 (82.72%) of the 81 children declared
      wetting during the day and 41 (50, 62%) - wetting during the night. 32/81 (39.5%)
      children had increased voiding frequency and 43 (53.08%) had decreased bladder
      capacity. Following 2 months of biofeedback therapy daytime incontinence resolved
      in 34/67 (50.7%) children and nighttime incontinence in 22/41 (53.65%). A further
      40,3% declared partial improvement in daytime and 26.7% in nighttime wetting.
      CONCLUSIONS: Biofeedback treatment is an effective therapeutic option for
      children with dysfunctional voiding. Pelvic floor therapy with biofeedback should
      be offered to children with dysfunctional voiding resistant to standard
      urotherapy.

PMID- 24578965
TI  - Split ejaculation study: semen parameters and calcium and magnesium in seminal
      plasma.
AB  - OBJECTIVES: Male infertility is on the rise. Artificial insemination is an option
      in many cases like oligozoospermia or oligoasthenozoospermia. Homologous
      insemination is helpful for some couples in whom sperm count is low. This study
      was aimed to understand the most suitable portion of split ejaculate for
      insemination and also the level of calcium and magnesium in each split. MATERIALS
      AND METHODS: A total number of 31 normal and clinically healthy adults
      participated in this study. They were instructed to maintain abstinence for 2-5
      days prior to sample collection in three splits. Each split was evaluated as if
      it were a whole sample, following WHO criteria. Seminal plasma was separated.
      Calcium and magnesium levels were measured in seminal plasma and spermatozoa of
      each split. RESULTS: The split ejaculate study revealed that the first portion
      contained a higher number of spermatozoa with better motility than the 2nd and
      3rd splits. Similarly, the level of calcium and magnesium in seminal plasma and
      spermatozoa was greater in the first split, followed by 2(nd) and 3(rd) splits.
      CONCLUSION: The presented split ejaculate study has shown the first ejaculate as
      superior in quality in terms of total sperm count and percentage of active
      motility. The first split of ejaculation is recommended for homologous artificial
      insemination in case of oligozoospermia and oligoasthenozoospermia. This study
      has also shown that a major portion of two important elements, calcium and
      magnesium, is contributed by the prostate gland.

PMID- 24578966
TI  - Acute pancreatitis as rare complication of the right radical transperitoneal open
      nephrectomy.
AB  - Radical open nephrectomy is considered the standard treatment for kidney tumors
      or masses greater than 10 cm. We present a rare case of acute pancreatitis that
      occurred after right radical transperitoneal nephrectomy, which was treated by
      nonsurgical conservative interventions. The incidence of acute pancreatitis after
      renal surgery is not known in the literature. A 56-year-old man developed acute
      pancreatitis postoperatively after radical transperitoneal nephrectomy. An
      initial CT scan showed an enlarged pancreas with hypodense, heterogeneous
      consistency and with peripancreatic, perihepatic, mesenteric, and pelvic fluid
      collections. This complication was managed conservatively. 

PMID- 24578967
TI  - A case of both clear and papillary renal cell carcinomas in the left kidney.
AB  - We present a patient with two types of renal cell carcinoma (clear and papillary)
      in the left kidney - nephrectomy was performed. Among the first symptoms, bone
      metastases occurred. As far as we know, this is the first reported case in
      literature with such an unexpected outcome, because the patient is still alive
      and feels good. 

PMID- 24578968
TI  - Minimally invasive treatment of prostatic abscess - percutaneous transvesical
      drainage.
AB  - We currently treat prostatic abscess with minimally invasive methods, most
      frequently with transurethral (TURP) or transrectal drainage under visual control
      with TRUS. We present an example of prostatic abscess drainage by percutaneous
      and transvesical means under the control of ultrasonography (USG). With a 9F
      single-stage drainage kit, the prostatic abscess was punctured through the
      abdominal skin and bladder in one step. We found this method to be
      straightforward for urology and safe for the patient. 

PMID- 24578969
TI  - A case of metastatic renal cell carcinoma treated effectively by gemcitabine and
      sunitinib.
AB  - A 60-year-old man with renal cell carcinoma developed lung metastases after
      treatment with left radical nephrectomy (pT3bN0M0, clear cell renal carcinoma,
      Fuhrman G3 >2). The patient received treatment with gemcitabine and interferon
      alpha and achieved complete response after seven cycles of therapy. However,
      eight months later, local recurrence was discovered in the renal fossa. We
      changed the therapeutic strategy to sunitinib, a multi-target tyrosine kinase
      inhibitor. The patient achieved a complete response after twelve cycles of
      therapy. This case report illustrates the effective use of gemcitabine and
      sunitinib sequentially for a patient with metastatic renal cell carcinoma. 

PMID- 24578970
TI  - Complications following endoscopic treatment of vesicoureteric reflux with
      Deflux((r)) - two case studies.
AB  - The endoscopic injection of vesicoureteric orifices with synthetic or natural
      materials is a widely recognized method of treating vesicoureteral reflux (VUR).
      The aim of this study is to present two cases of clinically significant
      complications following the use of dextranomer/hyaluronic acid copolymer, which
      led to the progression of the reflux degree, permanent infection of the urinary
      tract, and the necessity to perform surgical treatment. 

PMID- 24578971
TI  - Metastatic malignant melanoma of the urinary bladder: Case report and literature
      review.
AB  - Metastatic malignant melanoma of the urinary bladder is a rare clinical finding
      suggestive of advanced disease. Only 17 cases have been described in the English
      literature. We present a case of an 84-year-old male who was referred to the
      urology department with the incidental finding of bladder metastases on computed
      tomography (CT) one year following the diagnosis of malignant melanoma of the
      skin. Herein, we will discuss epidemiology, prognosis, and management options of
      metastatic malignant melanoma based on literature review. 

PMID- 24578972
TI  - Idiopathic spontaneous rupture of the urinary bladder (SRUB). A case report and
      review of literature.
AB  - Spontaneous rupture of the urinary bladder (SRUB) is a rare urological emergency.
      It is usually secondary to an underlying pathology. An idiopathic entity has not
      been reported in the literature. We report a case of idiopathic SRUB in a young
      female presented with abdominal pain and acute renal injury in the absence of
      prior trauma. We have conducted a literature review to identify commonly reported
      etiologies. SRUB is usually secondary to an underlying pathology, but in
      extremely rare cases it can be idiopathic. 

PMID- 24578973
TI  - Management of forgotten double J stent and severe multiple large encrusted stones
      in the bladder and renal pelvis.
AB  - A female patient from a remote village and poor socioeconomic background
      presented to our clinic with abdominal pain at the right flank. She had a history
      of endoscopic double J stent placement four years prior. However, the details
      were not available, as neither the patient nor her relatives were aware of the
      history. An ultrasonography was performed and revealed moderate hydronephrosis of
      the right kidney with two calculi measuring 2.9 cm at the pyeloureteral junction
      (PUJ), a 2.6 cm calculus in the renal pelvis, and a 4 cm vesicle calculus. An
      intravenous urography revealed delayed excretion of contrast medium in the right
      kidney. A cystoscopy was then performed and the lower end of the forgotten double
      J stent was cut along with the encrusted stone in bladder [1, 2]. Removal of the
      large encrusted bladder stone was aided by lithotripsy. This was followed by the
      removal of the two PUJ calculi and the remaining portion of the encrusted double
      J stent, which was extracted with relative ease via a right-sided open
      pyelolithotomy [3]. The post-operative course was uneventful and her kidney
      function test was absolutely normal following the procedures. The patient was
      found to be stone-free and was discharged home. In light of this situation we
      have deemed it necessary to maintain contact and ensure regular follow-up visits
      for patients with double J stent placements in order to avoid such dangerous
      complications in the future. By following this custom, we aim to reduce the
      patient morbidity and avoid any unnecessary inconvenience. 

PMID- 24578975
TI  - Bladder cancer - How to improve?

PMID- 24578974
TI  - 8-year survival in a patient with several recurrences of renal cell carcinoma
      after radical nephrectomy.
AB  - We describe the case of a patient with a large renal cell carcinoma (RCC) who
      underwent cytoreductive nephrectomy utilizing liver mobilization techniques
      similar to those used in transplantation. Despite recurrent metastases, our
      patient continues to survive eight years later with several metastasectomies and
      adjuvant chemotherapy. We report the case of a 48-year-old Hispanic American man
      who presented with a 4-month history of an enlarging right upper quadrant
      abdominal mass and hematuria. Computerized tomography revealed a 13 x 14 x 14
      centimeter mass suspicious of RCC with possible metastasis to the lungs. The
      patient subsequently underwent radical nephrectomy. Pathological analysis
      confirmed the mass as RCC. Over the following eight years, the patient developed
      metastases to the pulmonary lobes, buccal mucosa, thoracic spine, and second rib,
      which were all treated with metastasectomy. The patient continues to survive
      today with a reasonable quality of life. Palliative measures in patients with
      large RCC tumors with distant metastases require persistent, aggressive
      therapeutic modalities. 

PMID- 24578977
TI  - A role for pediatric oncologists/urologists?!

PMID- 24578976
TI  - Who needs numbers more: patients or doctors?

PMID- 24578978
TI  - Genetic polymorphism intermingled with environmental factors substantially
      contributes to the bladder cancer progression.

PMID- 24578980
TI  - Editorial comment.

PMID- 24578979
TI  - EORTC risk tables - their usefulness in the assessment of recurrence and
      progression risk in non-muscle-invasive bladder cancer in Polish patients.
AB  - INTRODUCTION: The assessment of risk of recurrence and progression of bladder
      cancer (BC) is still rather difficult. We decided to check the rates of the
      changes mentioned above in the group of the Polish patients after a year-long
      observation and next to compare them with the results calculated in the European
      Organisation of Research and Treatment of Cancer (EORTC) risk tables. METHODS:
      The tested group consisted of 91 patients who underwent transurethral resection
      of bladder tumour (TURBT). When being diagnosed, 60 cases were in the pTa
      clinical stage, whereas 30 cases were in T1. The coexisting carcinoma in situ
      (CIS) was observed in four cases. On the basis of the scores obtained from the
      EORTC tables, the patients were divided into the groups of low, intermediate or
      high risk of disease recurrence and progression. RESULTS: Recurrence was noticed
      in 23 patients (25%), while progression was observed in 11 patients (12.1%). The
      rate of the observed recurrences proved to be lower than it had been predicted in
      all the groups, except for one of the intermediate-risk group (score 1- 4).
      Moreover, the rate of the progressions predicted according to the EORTC risk
      tables was higher in all the risk groups. CONCLUSIONS: It can be noticed that the
      rate of real recurrences is lower than expected, whereas the rate of the observed
      progressions is overestimated. Partly, it could be the result of using a
      relatively small group of patients for observation and applying a different
      method of treatment.

PMID- 24578982
TI  - Editorial comment.

PMID- 24578981
TI  - Concomitance of oncogenic HPV types, CHEK2 gene mutations, and CYP1B1 gene
      polymorphism as an increased risk factor for malignancy.
AB  - INTRODUCTION: Urinary bladder carcinoma ranks the fourth position in malignancy
      incidence rates in men (6.1%) and the 17th position in women (1.6%). In general,
      neoplastic diseases should be approached from two perspectives: prevention with
      implementation of prophylactic measures and early diagnostics. Prophylactics is
      possible in the preclinical phase of neoplasm, being both justified and plausible
      in patients from high-risk groups. Thus, it is particularly important to select
      such groups, not only by referring to environmental carcinogenic factors
      (occupational and extra-occupational) but also from genetic predisposition, which
      may be conductive for neoplasm formation. The mutations / polymorphisms of CHEK2
      and CYP1B1 genes predispose to neoplasm via multiorgan mechanisms, while the
      human papilloma virus (HPV) may participate in the neoplastic transformation as
      an environmental factor. MATERIAL AND METHODS: 131 patients with diagnosed
      urinary bladder cancer were qualified to the study. Mutations/polymorphisms of
      CHEK2 (IVS2 + 1G > A gene, 1100delC, del5395, I157T) and CYP1B1- 355T/T were
      identified by the PCR in DNA isolated directly from the tumor and from peripheral
      blood. The ELISA test was used for the studies of 37 HPV genotypes in DNA,
      isolated tumour tissue. RESULTS: 11 mutations of CHEK2 gene were found, 355T/T
      polymorphism if CYP1B1 gene occurred in 18 patients (12.9%). Oncogenic HPV was
      found in 36 (29.3%), out of 123 examined patients. CONCLUSIONS: The concomitance
      of CHEK2 gene mutations or 355T/T polymorphism of CYP1B1 gene and the presence of
      oncogenic HPV types statistically significantly correlates with histological
      malignancy grades of urinary bladder carcinoma.

PMID- 24578984
TI  - Editorial comment.

PMID- 24578983
TI  - There is no place for targeted therapy neoadjuvant treatment in Polish Health
      System - An analysis of radical nephrectomies in patients with large kidney
      tumors.
AB  - INTRODUCTION: Despite the introduction of better diagnostic tools, very large
      kidney tumors are still not so rare in our country. The paper presents our
      experience in the treatment of 12 patients with kidney tumors larger than 14 cm
      in size. MATERIAL AND METHODS: Between spring 2009 and autumn 2011, radical
      nephrectomies were performed in 12 patients due to a large kidney tumor (larger
      than 14 cm in size). Symptoms (hematuria, weight loss, anemia, etc.) were not
      present in all the patients, but the kidney tumor was confirmed by imaging
      studies (ultrasound, CT, MRI) in all of them. RESULTS: Full recovery was observed
      with no severe complications in all of the patients treated with radical
      nephrectomy. Pathological staging was correctly established by imaging studies in
      all of them. After a few months, five of patients (41.6%) required systemic
      therapy due to lymph node involvement. CONCLUSIONS: Patients with large kidney
      tumors should be treated in selected medical centers that have experience in the
      treatment of such cases. Radical nephrectomy has to be the method of choice in
      the treatment of patients with this kind of tumor and its diameter should not
      disqualify from surgical treatment, which is still the only chance for the
      patients to be cured, as no adjuvant chemotherapy treatment has proved to be
      significantly effective.

PMID- 24578985
TI  - NSS for an RCC in a patient with renal insufficiency after heart transplant
      because of right ventricular tumor.
AB  - The effect of the immunosuppressive therapy on the development of neoplasms has
      become the object of an ever increasing interest for clinicians all over the
      world. The literature on neoplasms development in the course of therapy following
      transplants has confirmed a considerable increase in the incidence of neoplasms
      of the skin and lymph nodes. Organ neoplasms developing in patients after
      transplants are characterized by increased progression, poor cellular
      diversification and a more unfavorable prognosis than in the general population
      The aim of the study is to present the case of a nephron-sparing surgery of a
      renal tumor (NSS) without any intraoperative ischaemia in a 55-year-old female
      patient with an orthotopic heart transplant and renal insufficiency following a
      prolonged immune suppression. It is estimated that the patients at the highest
      risk of neoplasm development are those in the first months after transplant,
      especially heart transplant. They require maximum doses of immunosuppressive
      drugs. In the case of patients with initial renal insufficiency the duration of
      ischaemia of the organ operated on should be minimized, and if possible, surgery
      should be conducted without clamping the renal pedicle. The surgical treatment of
      RCC (renal cell carcinoma) in transplant patients does not require any reduction
      in the amount of the immunosuppressive drugs. 

PMID- 24578987
TI  - Unfavorable prognosis of nephroblastoma in adults.
AB  - Wilms' tumor is the most common type of malignant kidney tumor in children. Due
      to the fact that this type of cancer is so rare in adults, however, there is a
      significant lack of treatment strategies in this age group. Moreover, the
      treatment of adults is often based on protocols used in children. The present
      report describes a case of a 25-year-old male with nephroblastoma stage IV, who
      had a primary surgery and underwent chemotherapy with CDVC (cyclophosphamide,
      doxorubicin, vepesid, carboplatin). During the systemic treatment, the authors
      observed progression of disease and serious side effects. 

PMID- 24578986
TI  - Adult Wilms' tumor - diagnosis and current therapy.
AB  - INTRODUCTION: Wilms' tumour is one of the commonest malignant tumours of
      childhood. It appears mainly in the first 5 years of life. Incidental examples of
      nephroblastoma in adults have been described in literature (about 3% of all
      described cases). There are diagnostic and therapeutic difficulties in that older
      age group. The preoperative diagnosis of nephroblastoma in adults is difficult
      because there are no specific radiographic findings that allow to distinguished
      it from the more common adult renal tumors. Histopathologically, there is no
      difference between adult and childhood Wilms' tumor. MATERIALS AND METHODS: The
      PubMed database and current literature search was conducted for reports on
      clinical and histopathological features of nephroblastoma in adults. We also
      reviewed the literature in terms of treatment strategy, toxicity and prognostic
      factors. RESULTS: Up till now, several biological factors have been identified
      that may be in future new prognostic factors. Modern treatment regiments improved
      OS in this group of patients (OS rates of 90%). The prognosis remain still worse
      for about 25% of patients with anaplastic, bilateral and recurrent disease.
      CONCLUSIONS: Due to the fact that nephroblastoma is a very rare type of cancer,
      adult patients should be treated in an individual way based on the available
      schemes used in children. Toxicity in adults is higher than in children.

PMID- 24578988
TI  - Varicocelectomy and infertility.

PMID- 24578989
TI  - Sperm cyropreservation and oxidative damage. What does it mean?

PMID- 24578990
TI  - Clinical and laboratory profiles of a large cohort of patients with varicocoele.

PMID- 24578991
TI  - Cell phones give more benefits than risks, but....

PMID- 24578992
TI  - Testicular volume and fertility potential in men operated due to varicocele and
      testicular hypotrophy in adolescence.
AB  - INTRODUCTION: Failure to perform surgical repair of varicocele before puberty is
      among the common causes of male infertility. The purpose of this study was to
      evaluate the testicular volume and fertility potential in men after laparoscopic
      varicocelectomy conducted in adolescence due to varicocele and concomitant
      testicular hypotrophy. MATERIAL AND METHODS: From 1996 through 2011, eighty-two
      adolescents were operated on for unilateral primary varicocele with testicular
      hypotrophy. Sixty-eight patients were subject to the current analysis. The age of
      the patients was 13 to 17 years (mean 15.3 years). Clinical diagnosis was
      established on the basis of andrologic examination and ultrasonography with an
      assessment of testicular size and varicocele severity. Laparoscopic surgical
      repair was performed by a transperitoneal approach with division of testicular
      vein only. RESULTS: An increase in left testicular volume when compared with the
      contralateral testis was found in 25 (78.1%) young men with clinical grade 2
      varicocele (p = 0.02) and in 32 (88.8%) subjects with grade 3 abnormality (p =
      0.04). An increase in left testicular volume was found in 46 (85.1%) of 54
      patients with unilateral varicocele and in 12 (85.7%) of 14 subjects operated on
      for bilateral disease. A left testicular volume increase was comparable
      independent of the use of uni- or bilateral repair. Fifty-eight (85.2%) of our 68
      patients had normozoospermia. CONCLUSIONS: Laparoscopic varicocele repair
      resulted in a significant increase of hypotrophic testicular volume in 83.8% of
      our subjects.

PMID- 24578994
TI  - Editorial comment.

PMID- 24578995
TI  - Editorial comment.

PMID- 24578993
TI  - The role of oxidative stress and antioxidants in male fertility.
AB  - Oxidative stress results from the imbalance between production of the reactive
      oxygen species (ROS) and the protective effect of the antioxidant system
      responsible for their neutralization and removal. An excess of ROS causes a
      pathological reaction resulting in damage to cells and tissues. Spermatozoa are
      particularly vulnerable to the harmful effects of ROS. Oxidative stress affects
      their activity, damages DNA structure, and accelerates apoptosis, all of which
      consequently decrease their numbers, hinders motility and development of normal
      morphology, and impairs function. This leads to disturbances in fertility or
      embryo development disorder. The main cellular source of ROS in the semen are
      immature sperm cells and white blood cells. The increase in the number of
      leukocytes may be due to infection and inflammation, but can also be secondary to
      harmful environmental factors, long sexual abstinence, or varicocele. The
      protective antioxidant system in the semen is composed of enzymes, as well as
      nonenzymatic substances, which closely interact with each other to ensure optimal
      protection against ROS. Non-enzymatic antioxidants include vitamins A, E, C, and
      B complex, glutathione, pantothenic acid, coenzyme Q10 and carnitine, and
      micronutrients such as zinc, selenium, and copper. It seems that a deficiency of
      any of them can cause a decrease in total antioxidant status. In vitro and in
      vivo that studies demonstrate many antioxidants possess a beneficial effect on
      fertility and, therefore, their use is recommended as supportive therapy for the
      treatment of infertility in men. 

PMID- 24578996
TI  - Clinical and laboratory profiles of a large cohort of patients with different
      grades of varicocele.
AB  - OBJECTIVE: In this retrospective study we attempted to report our own data on the
      different clinical parameters in association with the presence and severity of
      varicocele in a large group of Austrian men. METHODS: The records of 1,111
      consecutive patients with clinical varicocele from 1993 to 2010 were evaluated.
      The presence, grade, and side of any varicocele were recorded. Semen samples,
      serum FSH, LH, and testosterone levels, and testicular volume were assessed.
      RESULTS: The mean age was 28.8 (+/-7.3) years. Three hundred seventeen (28.5%)
      patients presented with grade I varicocele, 427 (38.4%) with grade II varicocele,
      and 367 (33%) with grade III varicocele. Correlation between different grades of
      varicocele and semen quality indicated an over-representation of oligospermia and
      asthenoteratospermia in the group of grade III varicocele (p <0.05), whereas
      other parameters of semen quality showed no significant difference between the
      three groups. Serum testosterone levels and BMI were significantly associated (p
      <0.05) with the grade of varicocele, but no association was found with the other
      parameters analyzed. CONCLUSIONS: Our analysis showed a significant relationship
      between the grade of varicocele and semen analysis. Moreover, higher testosterone
      levels and lower body mass index were associated with the higher grade of
      varicocele and decreased semen quality. More prospective studies are recommended.

PMID- 24578997
TI  - Cell phone usage and erectile function.
AB  - INTRODUCTION: The objective of this pilot study was to report our experience
      concerning the effects of cell phone usage on erectile function (EF) in men.
      MATERIAL AND METHODS: We recruited 20 consecutive men complaining of erectile
      dysfunction (ED) for at least six months (Group A), and another group of 10
      healthy men with no complaints of ED (Group B). Anamnesis, basic laboratory
      investigations, and clinical examinations were performed. All men completed the
      German version of the Sexual Health Inventory for Men (SHIM) for evaluation of
      the International Index of Erectile Function (IIEF), as well as another
      questionnaire designed by our clinicians that assessed cell phone usage habits.
      RESULTS: There was no significant difference between both groups regarding age,
      weight, height, and total testosterone (Table 1). The SHIM scores of Group A were
      significantly lower than that of Group B, 11.2 +/-5 and 24.2 +/-2.3,
      respectively. Total time spent talking on the cell phone per week was not
      significantly higher in Group A over B, 17.6 +/-11.1 vs. 12.5 +/-7 hours. Men
      with ED were found to carry their 'switched on' cell phones for a significantly
      longer time than those without ED, 4.4 +/-3.6 vs. 1.8 +/-1 hours per day.
      CONCLUSIONS: We found a potential correlation with cell phone usage and a
      negative impact on EF. Further large-scale studies confirming our initial data
      and exploring the mechanisms involved in this phenomenon are recommended.

PMID- 24578998
TI  - Editorial comment.

PMID- 24578999
TI  - Should every patient with hematospermia be investigated? A critical review.
AB  - Hematospermia or hemospermia is defined as the presence of blood in ejaculate. It
      often invokes considerable anxiety and is frightening for the patient. Mostly, it
      is due to infectious causes and regarded as a benign and self-limiting condition
      particularly in younger patients. Patients above 40 years of age and those with
      high risk factors require thorough evaluation. Detailed examination is mandatory,
      and should include: blood pressure measurement and abdominal palpation to
      identify hepatosplenomegaly or renal enlargement. Genital examination must also
      be performed to assess for the presence of testicular lumps and urethral
      discharge, as well as a rectal examination to assess the prostate. Further
      investigations include cystoscopy, transrectal ultrasound, and prostate biopsy.
      Diagnosing prostatic pathologies is made easier by performing transrectal
      ultrasound. It is useful in diagnosing calculi, cysts, prostatic varices, and
      inflammatory changes, as well as therapeutic in certain cases where cyst or
      abscess is drained and is found to be the cause of hematospermia. Complex
      investigations depend on history and examination. A role of MRI is emerging to
      rule out rare causes of hematospermia. Evidence based evaluation of hematospermia
      is not only useful in definitive diagnosis, but it can also be cost effective.
      Therefore, we suggest that patients with high risk factors should be investigated
      thoroughly. However, younger patients with one episode can be monitored closely
      and investigated only if deemed necessary. 

PMID- 24579000
TI  - Editorial comment.

PMID- 24579001
TI  - Editorial comment.

PMID- 24579002
TI  - Correlation between seminal lead and cadmium and seminal parameters in idiopathic
      oligoasthenozoospermic males.
AB  - INTRODUCTION: The exact causes of the decline in semen quality are not yet known,
      environmental factors have been considered to play an important role. Lead (Pb)
      and Cadmium (Cd) are two of the well-known reproductive toxicants to which humans
      are exposed occupationally and environmentally and can lead to negative effects
      on the testicular functions. The aim of this study was to evaluate lead and
      cadmium levels in seminal plasma of men with idiopathic oligoasthenozoospermia in
      comparison to fertile healthy controls and to correlate these levels with
      conventional semen parameters, sperm hypo-osmotic swelling (HOS) percentage,
      sperm DNA fragmentation percentage, and semen reactive oxygen species (ROS)
      levels. MATERIAL AND METHODS: Thirty infertile male patients with idiopathic
      oligo and/or asthenozoospermia and thirty healthy fertile men, which was the
      control group, were included in the study. Lead and cadmium levels in seminal
      plasma, semen parameters, sperm HOS, sperm DNA fragmentation percentage and semen
      ROS assay were measured in all subjects. RESULTS: There was a significant
      increase in seminal lead and cadmium levels among infertile males in comparison
      to controls. There were significant negative correlations between seminal lead
      and cadmium levels on one hand and certain semen parameters especially
      progressive sperm motility and vitality (HOS). Importantly, significant positive
      correlations were noted between seminal lead and cadmium levels on one hand and
      sperm DNA fragmentation percentage and semen ROS level in infertile men and
      controls on the other hand. CONCLUSIONS: Thus, men with idiopathic male
      infertility had higher levels of lead and cadmium in their semen which correlated
      with impairment of sperm motility and vitality percentages and more importantly
      with higher sperm DNA fragmentation% and semen ROS level.

PMID- 24579003
TI  - Mental status in patients with chronic bacterial prostatitis.
AB  - INTRODUCTION: Chronic prostatitis is a widespread urological disease with a
      lengthy course and a propensity to frequent recurrences. Adequate response to
      anti-inflammatory therapy is lacking in a high percentage of patients, which
      causes them to seek medical advice from different doctors. Thus, the physicians
      are challenged to look for other reasons causing the pathological symptoms.
      MATERIAL AND METHODS: We have reviewed the patients with treatment-resistant
      chronic bacterial prostatitis (CBP) from the perspective of psychosomatic
      medicine. For the evaluation of primary mental status and treatment control we
      used standard approved questionnaires. All 337 CBP patients initially underwent
      therapy aimed at pathogen eradication. If psychopathological symptoms were
      evident and dominated over urological ones, the patients were referred to
      psychiatric evaluation and treatment. RESULTS: The frequency of concomitant
      psychosomatic disorders (PSD) in patients with CBP was 28.2% and neurotic
      disorders - 26.4%. Adequate multimodal anti-inflammatory therapy followed by a
      few sessions of psychotherapy decreased the manifestations of PSD in 30.5%,
      neurotic disorders in 51.7%, and premature ejaculation in 60.5% of patients with
      CBP. The addition of pharmacotherapy to psychotherapy is effective in treatment
      resistant cases. However, after multimodal treatment, 31.5% of pts. with PSD and
      13.5% of pts. with neurotic disorders still remain treatment-resistant and
      required in-depth long-term psychiatric care. CONCLUSIONS: A significant portion
      of CBP patients were diagnosed with neurotic, psychosomatic, and/or depressive
      disorders. Antibacterial and anti-inflammatory therapy, when followed by
      appropriate psychotherapy and pharmacotherapy, significantly decrease the
      manifestations of mental disorders in CBP patients.

PMID- 24579004
TI  - An uncommon case of inflammatory infiltration of the urinary bladder in the long
      term process of the purulent inflammation of the cervix and vaginal fornix,
      complicated with vesicovaginal fistula of unknown etiology.
AB  - We shall discuss the case of a female patient, aged 64 years, who was suffering
      from long-term purulent inflammation of the vaginal fornix that later involved
      the vaginal stump. This inflammatory process spread to the bladder trigone and
      resulted in vesicovaginal fistula (VVF) formation together with a bilateral
      hydronephrosis that required the placement of a temporary percutaneous
      nephrostomy. A non-cicatrized inflammatory reaction occurred at the right-sided
      insertion of the nephrostomy, which has yet to be successfully treated despite
      intensive dermatological and surgical approaches that included skin grafting. In
      the course of five-year treatment we observed a gradual regression of the
      inflammatory infiltration of both the trigone of the bladder and the vagina as
      well as a gradual closing of the VVF. The extremely long-lasting and uncommon
      local inflammatory reactions in the vagina, bladder, and dermal layers mandated
      the application of conservative treatment. The possibility of difficulties and
      defective healing of tissues that could result from surgical correction of the
      VVF are discouraging for both the patient and medical staff. 

PMID- 24579005
TI  - Complications after primary bladder exstrophy closure - role of pelvic osteotomy.
AB  - INTRODUCTION: Bladder exstrophy is the most common form of the exstrophy -
      epispadias complex. It is observed in 1:30 000 life births, about four times more
      often in boys than in girls. Iliac osteotomy is used to facilitate bringing
      together pubic bones and to minimize the tension of fused elements. To analyze
      complications after primary bladder exstrophy closure with a special
      consideration of the role of pelvic osteotomy. MATERIAL AND METHOD: It is a
      retrospective study evaluating 100 patients (chosen by chance out of 356) with
      bladder exstrophy (65 boys and 35 girls), treated in Pediatric Urology Department
      of the Children's Memorial Health Institute in Warsaw, Poland between 1982 and
      2006. All children underwent primary bladder exstrophy closure, among them 32
      elsewhere. Primary bladder exstrophy closure with contemporary iliac osteotomy
      was done in 36 children. In the rest 64 patients bladder was closed without
      osteotomy, regardless child's age. RESULTS: Dehiscence after primary closure
      followed with bladder prolaps occurred in 31 patients, among them 13 out of 68
      (19%) operated in our department and 18 out of 32 (56%) operated in another
      hospital. Primary bladder exstrophy closure with contemporary iliac osteotomy was
      done in 32 infants above 72 hours of life. CONCLUSIONS: Osteotomy performed at
      primary bladder exstrophy closure diminishes the risk of wound dehiscence
      independently of patient's age. Posterior iliac osteotomy is sufficient and safe
      and could be repeated if necessary.

PMID- 24579006
TI  - Editorial comment.

PMID- 24579007
TI  - Author'S replay.

PMID- 24579008
TI  - Some thoughts on the effect of non-linearity on innovation in urological surgery.

PMID- 24579010
TI  - Prostate cancer recurrence - new prognostic factors are needed.

PMID- 24579011
TI  - Author'S reply.

PMID- 24579009
TI  - Low pre-operative levels of serum albumin predict lymph node metastases and
      ultimately correlate with a biochemical recurrence of prostate cancer in radical
      prostatectomy patients.
AB  - INTRODUCTION: To date, only few studies focusing on the issue of host general and
      immune activity have been performed in localized prostate cancer (PCa). The aim
      of this study was to elucidate potent non tumor-related biomarkers that express
      aggressiveness of PCa treated by radical prostatectomy (RP). MATERIALS AND
      METHODS: Data from 179 patients who underwent RP were analyzed. The correlations
      between various kinds of non tumor-related factors in addition to tumor-related
      factors and biochemical recurrence (BCR) were analyzed. The correlations between
      pre-, intra- and post-operative factors were also analyzed. RESULTS: Thirty-two
      cases (17.9%) had a BCR. The factors found to be significantly predictive of BCR
      using a Cox-proportional hazard model were the pre-operative serum prostate
      specific antigen (PSA) level and the existence of pathological lymph node
      metastasis (LNM). A low pre-operative serum albumin level (<4.0 g/dl) was
      significantly correlated with BCR univariately. Logistic regression analysis
      revealed that a low pre-operative serum albumin level, an American Society of
      Anesthesiologists (ASA) score above class 2, and a Gleason score above 8 in the
      biopsy specimens were significantly predictive of pathological LNM. CONCLUSIONS:
      Tumor-related characteristics are more important for predicting BCR. However, our
      results suggest that low pre-operative serum albumin level may indicate extensive
      disease of clinically localized PCa and may ultimately be correlated with BCR.
      Although multiple reasons may account for the significance of the serum albumin
      level, it is noteworthy that delayed diagnostic and therapeutic procedures in
      comorbid patients with low serum albumin levels may lead to PCa progression.

PMID- 24579013
TI  - From industrial laboratory directly to operating table: the vicissitudes of
      optical coherence tomography (OCT).

PMID- 24579012
TI  - Optical coherence tomography diagnostics for onco-urology. Review of clinical
      perspectives.
AB  - INTRODUCTION: Optical coherence tomography (OCT) is being investigated widely for
      use in urologic pathology. The current imaging of urogenital cancers cannot be
      perfect, thus, routine methods demands new updates or inventions of alternative
      radiological scope. OCT presents so-called "live" optical biopsy. The authors aim
      to review this modality for uro-oncological purposes. MATERIAL AND METHODS:
      [corrected] A series of 37 publications between 1989 and 2012 was selected and
      cited from GoogleScholar and PubMED/MEDLINE. The urogenital tract (bladder,
      ureter, scrotum organs and prostate) was imaged by OCT. RESULTS: The overall OCT
      sensitivity, specificity, accuracy, negative and positive predictive values
      ranged a lot on example of the urinary bladder's tumors screening. The data were
      75-100%, 65-97.9%, 92%, 75%, 100%, respectively. Notwithstanding, a diagnostic
      importance of OCT may be comparable with urine cytology, cystoscopy, computerized
      tomography and magnetic resonance imaging. CONCLUSIONS: OCT demonstrated its
      imaging potential, while till the present OCT plays role of an additional
      imaging. Future progress of OCT involvement in experimental and clinical once
      urological diagnostics is needed under high evidence control.

PMID- 24579015
TI  - Resveratrol in prostate diseases.

PMID- 24579017
TI  - The next step in nephron sparing surgery: vascular positioning system.

PMID- 24579016
TI  - Methodology and evaluation of the renal arterial system.
AB  - INTRODUCTION: The broad range of medical images and image processing technologies
      are applied in urology. The aim was to propose methodology to assess three
      dimensional (3D) arrangement of renal arterial tree and to build a statistical
      model for analyzing the layout of arteries in the sections of the kidney.
      METHODS: The series of kidney CT slices are analyzed using image processing
      procedures and further the 3D model of arterial systems is converted to a graph
      tree which includes information about features of the renal arterial system.
      RESULTS: The selected endocast was transformed to the form of the 3D connected
      tubes, further to the tree data structure and next analyzed. The information
      about 3D coordinates of the nodes, also branch length and diameter were stored.
      Renal arterial system of the considered kidney possessed 181 branches with 14
      bifurcation levels. The number of branches was highest at the 9th bifurcation
      level. The mean length of the arterial branch on each bifurcation level was
      constant (6 mm). The branch diameters rapidly decreased after each bifurcation.
      The number of terminal branches increases up to 9th level where there are 19
      terminal branches. The mean length of terminal arteries was 7.17 mm while the
      mean radius 0.46 mm. A statistically significant correlation between parameters
      that described sub-trees was noticed. It was observed that the individual artery
      segments occupy a separate space in the kidney volume. CONCLUSIONS: The
      methodology has the potential to assist in presurgical planning based on
      branching patterns of the renal arterial system and corresponding pathology.

PMID- 24579014
TI  - Resveratrol in prostate diseases - a short review.
AB  - INTRODUCTION: Resveratrol is a plant-derived polyphenol suggested to have many
      beneficial health effects, including antioxidant, anti-inflammatory, anti
      proliferative, proapoptotic, and anti-angiogenic. It is even specu- lated that
      uptake of resveratrol by red wine consumption could be behind the so-called
      French paradox the lower incidence of cardiovascular diseases in the French
      population. These properties, together with good absorption and tolerance, would
      make it an attractive agent in prostatic diseases, especially in cancer
      prevention and treatment. MATERIAL AND METHODS: MEDLINE search (keywords
      "prostate res- veratrol") resulted in 39 research papers published since 2007. It
      has been shown that resveratol down-regulate androgen receptor expression,
      inhibit proliferation, and promote apop- tosis in prostate cancer cell lines and
      enhance their sensitivity to ionizing radiation. Several studies on animal
      prostate cancer development also suggest that resveratrol is able do delay or
      prevent carcino- genesis in prostate. Despite these promising results, there is
      no proof of any therapeutic properties of resveratrol in prostate diseases from
      human clinical trials nor any information about ongoing trials in this field.
      CONCLUSIONS: Resveratrol is produced and sold as a nutritional supplement, there
      is not enough clinical evidence to justify a recommendation for the
      administration of resveratrol in humans at present.

PMID- 24579018
TI  - Partial cystectomy in a 76 year old patient suffering from small cell carcinoma
      of the urinary bladder.
AB  - Small cell carcinomas of the urinary bladder originating from the neuroendocrine
      cells are extremely rare. We present a case of a 76-year-old patient with small
      cell carcinoma of the urinary bladder. The patient had hematuria and cystoscopy
      revealed a tumor located in a urinary bladder diverticulum. Partial resection of
      the bladder wall with diverticulectomy was performed. Microscopic examination
      established the diagnosis of neuroendocrine carcinoma, which was confirmed by
      immunohistochemistry. Three-month follow-up showed no recurrent disease. Patient
      refused further chemotherapy and radiotherapy. 

PMID- 24579019
TI  - Following the guidelines is the easiest and safest of all, but life is not easy.

PMID- 24579020
TI  - An incidentally diagnosed prostatic ductal adenocarcinoma.
AB  - Ductal adenocarcinoma of the prostate was initially described in 1967 by Melicow
      and Patcher. It was given the erroneous name endometrioid carcinoma, however,
      further studies confirmed the prostatic origin of this tumor. Currently DAP is
      classified as a histological variant of prostatic carcinoma. Compared with
      "classic" acinar carcinoma of the prostate, DAP is a rare histological finding.
      It's prevalence in prostatectomy and biopsy specimens varies from less than 1%
      for pure ductal adenocarcinoma up to 5% for mixed DAP. Because of its typical
      periurethral location, the tumor usually manifests itself clinically with urinary
      obstruction, urinary urgency, urinary frequency and hematuria. DAP is associated
      with more aggressive natural history and worse prognosis than pure AA - patients
      presented at more advanced stage, with poorly differentiated and distant disease.
      DAP has a tendency to spread to regional lymph nodes, axial skeleton, and
      visceral organs. We report a case of a 90-year old man who presented to our
      clinic with acute urinary retention and gross hematuria. He underwent suprapubic
      transvesical adenomectomy to diminish the urinary obstruction. The pathological
      examination of the specimens revealed a dominant focus of DAP, which was located
      near the intraprostatic urethra and a coexisting, smaller component of "classic"
      acinar adenocarcinoma. 

PMID- 24579021
TI  - Benign fibroepithelial polyp of the ureter.
AB  - Benign tumors of the ureter are rare and most often appear in the form of
      fibroepithelial polyps [1]. Fibroepithelial polyps represent from 2 to 6% of all
      benign tumors of the urinary tract [2]. The Authors report on two cases of
      fibroepithelial polyps of the ureter, which they treated between 1993-2009. One
      case was presented by acute urinary retention and gross hematuria. In the second
      case, hematuria and flank pain were observed. The first case was treated with
      open surgery and partial resection of the ureter, the second was treated
      endoscopically when the base of the polyp was well identified. 

PMID- 24579022
TI  - Search for a cause of disseminated intravascular coagulopathy resulted in finding
      metastatic prostate cancer.
AB  - Disseminated intravascular coagulopathy (DIC) is an acquired disease that occurs
      secondary to a variety of underlying conditions including solid tumors. Prostate
      cancer (PCa) is one of these tumors and DIC is the most prevalent coagulopathy
      related to PCa, but it is rarely reported as the first manifestation of it. This
      paper is a report of an 85-year-old man who presented with hematuria and vast
      ecchymoses. Thorough work-up resulted in finding metastatic PCa with DIC as
      presenting condition. Although DIC is a rare manifestation of metastatic prostate
      cancer, it should be consider when no other reason can be found to explain it. 

PMID- 24579023
TI  - Bladder metastasis from primary breast cancer: a case report and literature
      review.
AB  - Breast cancer is the most common malignancy in woman. The urinary bladder is an
      unusual site for metastasis from primary tumors of the breast, especially when it
      is the only organ involved. We present the case of a female patient with known
      breast cancer stage T2N3M0 who developed isolated bladder metastasis five years
      after the primary diagnosis. We reviewed the literature for similar cases and
      discussed the clinical presentation, pathophysiology, and prognosis of this
      entity. 

PMID- 24579024
TI  - Muscle-invasive bladder cancer in a young adult: a case report and a review of
      the literature.
AB  - The peak incidence of bladder cancer (BC) is in the sixth decade of life. Muscle
      invasive bladder cancer (MIBC) in young adults is extremely rare. We report a
      case of MIBC in a 28-year-old smoking male patient. The patient presented with
      hematuria and flank pain for which he underwent a computerized tomography (CT)
      scan of the abdomen and pelvis with and without contrast. The CT scan showed a 6
      cm mass on the left side of the trigone extending to the left urteric orifice and
      left hydronephrosis, but no lymphadenopathy was noted. The patient then underwent
      a left nephrostomy tube placement followed by trans-urethral resection of bladder
      tumor (TURBT). The tumor involved both ureteric orifices and extended to the
      prostatic urethra. Complete resection was not feasible. Pathology showed high
      grade T1 urothelial carcinoma. CT scan of the chest showed no distant lung
      metastasis. The patient then elected to undergo radical cystectomy with ileal
      conduit urinary diversion. Final pathology revealed T2a N0 urothelial carcinoma
      of the bladder. Our aim is to present our experience and review the literature
      for the natural history and oncological and quality of life outcomes of
      urothelial carcinoma of the bladder in young patients. 

PMID- 24579026
TI  - Alpha-blocker and apoptosis.

PMID- 24579025
TI  - alpha-blockade, apoptosis, and prostate shrinkage: how are they related?
AB  - PURPOSE: The alpha1-adrenoreceptor antagonists, such as terazosin and doxazosin,
      induce prostate programmed cell death (apoptosis) within prostate epithelial and
      stromal cells in vitro. This treatment should cause prostate volume decrease,
      However, this has never been observed in clinical conditions. The aim of this
      paper is to review the disconnect between these two processes. METHODS: PubMed
      and DOAJ were searched for papers related to prostate, apoptosis, and stem cell
      death. The following key words were used: prostate, benign prostate hyperplasia,
      programmed cell death, apoptosis, cell death, alpha1-adrenoreceptor antagonist,
      alpha-blockade, prostate epithelium, prostate stroma, stem cells, progenitors,
      and in vitro models. RESULTS: We have shown how discoveries related to stem cells
      can influence our understanding of alpha-blockade treatment for BPH patients.
      Prostate epithelial and mesenchymal compartments have stem (progenitors) and
      differentiating cells. These compartments are described in relation to
      experimental in vitro and in vivo settings. CONCLUSIONS: Apoptosis is observed
      within prostate tissue, but this effect has no clinical significance and cannot
      lead to prostate shrinkage. In part, this is due to stem cells that are
      responsible for prostate tissue regeneration and are resistant to apoptosis
      triggered by alpha1-receptor antagonists.

PMID- 24579027
TI  - Chronic prostatitis/chronic pelvic pain syndrome: the role of an antifungal
      regimen.
AB  - INTRODUCTION: The role of fungal infection as a causative factor for prostatitis
      is currently underestimated. The aim of our work was to evaluate the response to
      an antifungal regimen in the setting of patients presenting with symptoms of
      chronic pelvic pain syndrome that have been refractory to treatment with
      antibiotics and alpha-blockers. MATERIAL AND METHODS: We included 1,000
      consecutive patients. The inclusion criteria included failure of response to four
      consecutive weeks of antibiotic and alpha-blockers. The antifungal regimen was
      continued for two weeks. It included a low carbohydrate diet, the alkalinization
      of urine, and administration of fluconazole. RESULTS: The mean age of the
      patients was 34 years. Mean serum total PSA and PSA density (PSAd) were 0.6 ng/ml
      and 0.03 ng/ml/gram, respectively. The mean age, PSA, prostate volume, and PSAd
      for patients that showed good response were 33, 0.5, 17, and 0.031, respectively.
      Values for patients that did not show good response were 36, 0.8, 23, and 0.037,
      respectively (p <0.0001 for all of the variables). Improvement was observed in
      80% of cases treated with the antifungal regimen. CONCLUSIONS: Antifungal regimen
      should be considered for the majority of young adult men, presenting with chronic
      prostatitis/ chronic pelvic pain syndrome and incomplete response to antibiotics.

PMID- 24579028
TI  - Antifungal azoles - new antidote for chronic pelvic pain?

PMID- 24579030
TI  - Is a functional urinary bladder attainable through current regenerative medicine
      strategies?

PMID- 24579029
TI  - Tissue engineering of urinary bladder - current state of art and future
      perspectives.
AB  - INTRODUCTION: Tissue engineering and biomaterials science currently offer the
      technology needed to replace the urinary tract wall. This review addresses
      current achievements and barriers for the regeneration of the urinary blad- der
      based on tissue engineering methods. MATERIALS AND METHODS: Medline was search
      for urinary bladder tissue engineering regenerative medicine and stem cells.
      RESULTS: Numerous studies to develop a substitute for the native urinary bladder
      wall us- ing the tissue engineering approach are ongoing. Stem cells combined
      with biomaterials open new treatment methods, including even de novo urinary
      bladder construction. However, there are still many issues before advances in
      tissue engineering can be introduced for clinical application. CONCLUSIONS:
      Before tissue engineering techniques could be recognize as effective and safe for
      patients, more research stud- ies performed on large animal models and with long
      follow-up are needed to carry on in the future.

PMID- 24579032
TI  - Intracavernosal injections in the diagnosis and treatment of PDE-5 resistant
      erectile dysfunction.

PMID- 24579031
TI  - A study of the possible effects of repeated intracorporeal self-injection of
      vasoactive drugs in patients with elevated end diastolic velocity during
      pharmacopenile duplex ultrasonography.
AB  - INTRODUCTION: The aim of the work is to evaluate the effect of repeated
      intracavernosal self-injection of vasoactive drugs in patients with elevated End
      Diastolic Velocity (>5 cm/sec) during pharmacopenile duplex ultrasonography
      (PPDU). METHODS: Duplex evaluation was performed to the patients on self
      injection therapy for comparison of end diastolic velocity and resistive index
      before and after completing the eight doses of IC self-injection. RESULTS: After
      the 8 trials of home therapy, 21 (52.5%) patients showed improvement in the
      duplex parameters regarding the end diastolic velocity, ten of them showed
      improvement in the EDV to the level of <5 cm/sec. The effect of different factors
      that may contribute to the improvement in EDV to <5 cm/sec are shown in the table
      2. Age was the only predictive factor for successful response to home therapy
      intracavernous injection (ICI). Improvement in erectile response was assessed
      before and after the course of the therapy. Erection response to ICI during
      penile duplex improved in only six patients (E4 & E4-5)) to the point that it was
      sufficient for satisfactory sexual performance, 3 of them (7.5%) regained
      spontaneous erection and stopped using ICI (table 3). The IIEF score was 10.6 +/
      2.8 before the home therapy and it became 14 +/-3.9 one month after completing
      the treatment course (P value <0.001). CONCLUSIONS: Early rehabilitation of the
      patients with venous leakage ED using ICI may help to regain normal erection and
      avoid unnecessary penile prosthesis surgeries.

PMID- 24579033
TI  - Familial appearance of congenital penile curvature - case history of two
      brothers.
AB  - The true prevalence of congenital penile curvature (CPC) is difficult to
      determine. Some study reports suggests that this problem may occur in as many as
      10% of the male population [1]. However, a literature search of the Medline
      database revealed no reference concerning familial appearance of congenital
      penile curvature. For that reason we would like to present our case series. Two
      brothers aged 25 and 26 respectively were admitted to the department of urology
      due to congenital penile curvature. Each patient was assessed by a history,
      physical examination, auto-photography of the erect penis, and a thorough sexual
      history. Concomitant anomalies of penile layers were absent in both cases. The
      Yachia [2] and Essed-Schroeder [3] corporoplasty technique were applied
      respectively. In follow-up both brothers reported straight erections. A survey of
      the fetal penis at different stages of development shows some degree of curvature
      in a considerable number of embryos [4]. Penile curvature may thus be considered
      almost physiological in embryos between 35 and 45 mm in length. Thus, it has also
      been proposed that penile curvature is secondary to an arrest in normal penile
      development [5]. Therefore, some form of congenital local androgen deficiency may
      be responsible for inherited penile curvature. 

PMID- 24579034
TI  - Asymptomatic hypospadias with tight meatal stricture in the father of twelve
      children.
AB  - Hypospadias is a highly prevalent congenital anomaly. English articles, indexed
      in PubMed, published the long-term sexual and reproductive outcome following
      hypospadias repair. Almost all repairable cases of hypospadias are operated in
      childhood. Although distal hypospadias does not interfere with fertility, it is
      worthy reporting a case of an elderly man, who fathers 12 children and has no
      urologic complaint, presented with unrepaired coronal hypospadias and severely
      tight external urethral meatus. 

PMID- 24579035
TI  - Neoadjuvant human Chorionic Gonadotropin (hCG) therapy may improve the position
      of undescended testis: a preliminary report.
AB  - INTRODUCTION: Treatment of cryptorchidism includes hormonal therapy and/or
      operative methods. To evaluate effectiveness of neoadjuvant hCG-therapy in
      cryptorchid boys regarding testicle position before and after treatment. MATERIAL
      AND METHODS: 204 boys with 229 UDT, median age at presentation 6,6 years, SD +/
      3.4; 179 (87.7%) with unilateral and 25 (12.3%) with bilateral defect were
      treated between 1994 and 2008. 103 boys (119 gonads - 51.9%) underwent orchiopexy
      alone, while 101 boys (110 gonads - 48.1%) neoadjuvant hCG-therapy. The testicle
      position was evaluated before and one year after therapy. Every patient was seen
      in our outpatient department 2 to 16 years after the therapy. RESULTS: Out of 110
      testes of 101 boys after hCG-therapy, 49 testicles (44.5%) descended to the
      scrotum and these 44 patients were not qualified for orchiopexy. Remaining 61
      testes (55.5%) did not reach the scrotum after hormonal therapy and these 57 boys
      underwent orchiopexy. Gonadotropin induced the descent of 90 out of 110 testicles
      at least one level down, therefore overall effectiveness of hCG therapy was 81.8%
      (chi = 29.778, p = 0.000). 49 out of 110 UDT descended to the scrotum (44.5%).
      The efficacy of hormonal treatment did not depended on initial position of UDT (p
      = 0.43, p = 0.04, p = 0.97). We performed only 7 orchidectomies of disgenetic
      testes (3.1%). Neither type of treatment nor initial position of testicle
      influenced the future gonad atrophy (p = 0.5, p = 0.979). CONCLUSIONS:
      Neoadjuvant hCG-therapy induced descent to the scrotum of 44.5% UDT and improved
      position of testis before orchidopexy in further 37.3% of patients.

PMID- 24579036
TI  - Neo-adjuvant hormonal treatment for the undescendent testis - a benefit for the
      patient?

PMID- 24579037
TI  - Grade IV renal trauma in a 17-year-old patient.
AB  - Renal trauma occurs in 1-5% of all trauma cases. The kidney is the most commonly
      injured genitourinary and abdominal organ. In this case we present a 17-year-old
      patient with a grade IV trauma of the left kidney with renal rupture, hematoma,
      and urinoma. He was referred to our hospital in hemodynamic stability; therefore,
      a conservative approach was chosen. One year after the accident the patient was
      free from symptoms, and the renal function was normal; CT-scan revealed neither
      hematoma nor urinoma. Since nothing is known on the long-term outcomes in
      patients with severe renal traumas, long-term follow up studies are highly
      recommended. 

PMID- 24579038
TI  - A case of polytrauma with splenic rupture and complete left renal artery
      avulsion.
AB  - This study presents a case of avulsion of the left renal artery from the aorta
      and splenic rupture after blunt abdominal trauma accompanied by an extensive
      crush syndrome. Based on contrast-enhanced abdominal ultrasound and computed
      tomography CT, the patient was qualified for urgent surgical intervention with
      removal of the injured kidney and spleen. 

PMID- 24579039
TI  - Ureterocolic fistula secondary to a self-expanding retrievable ureteral stent.
AB  - Self-expanding stents are relatively new in the field of urology and have
      primarily been used for permanent remodeling of benign or malignant stricture. We
      are presenting a rare and interesting case of a ureterocolic fistula that formed
      secondary to placement of an expandable, retrievable metal stent in the ureter.
      After multiple retrieval efforts, the self-expanding metal stent was finally
      retrieved and a ureterocolic fistula was appreciated on antegrade pyelography.
      The patient chose to manage it non-surgically, with routine nephroureteral
      catheter exchanges, and her creatinine continues to remain stable. 

PMID- 24579040
TI  - Strangulation of the penis: two case reports.
AB  - Till now numerous reports have depicted the different constricting devices (CDs)
      previously threaded on the penis for obtaining of sexual pleasure or/and
      prolonged erection. The causes of CD bearing on the penis are sexual or
      autoerotic actions. Here we present two cases of successful removal of a metal
      device from a penis that was associated with trauma grade II according to Bhat et
      al. The techniques used are also described. In both cases the essential features
      of successful device removal were its motionless fixation by nippers or vice
      combined with placing a metal plate under the constricting ring. The CDs were
      successfully removed without complications. 

PMID- 24579042
TI  - Stresses and Disability in Depression across Gender.
AB  - Depression, though generally episodic, results in lasting disability, distress,
      and burden. Rising prevalence of depression and suicide in the context of
      epidemiological transition demands more attention to social dimensions like
      gender related stresses, dysfunction, and their role in outcome of depression.
      Cross-sectional and follow-up assessment of men and women with depression at a
      psychiatric tertiary centre was undertaken to compare their illness
      characteristics including suicidal ideation, stresses, and functioning on GAF,
      SOFAS, and GARF scales (N = 107). We reassessed the patients on HDRS-17 after 6
      weeks of treatment. Paired t-test and chi-square test of significance were used
      to compare the two groups, both before and after treatment. Interpersonal and
      marital stresses were reported more commonly by women (P < 0.001) and financial
      stresses by men (P < 0.001) though relational functioning was equally impaired in
      both. Women had suffered stresses for significantly longer duration (P = 0.0038).
      Men had more impairment in social and occupational functioning compared to
      females (P = 0.0062). History of suicide attempts was significantly associated
      with more severe depression and lower levels of functioning in case of females
      with untreated depression. Significant cross-gender differences in stresses,
      their duration, and types of dysfunction mandate focusing on these aspects over
      and above the criterion-based diagnosis. 

PMID- 24579043
TI  - Hypospadias repair: a single centre experience.
AB  - Objectives. To determine the demographics and analyze the management and factors
      influencing the postoperative complications of hypospadias repair. Settings.
      Hayatabad Medical Complex Peshawar, Pakistan, from January 2007 to December 2011.
      Material and Methods. All male patients presenting with hypospadias irrespective
      of their ages were included in the study. The data were acquired from the
      hospital's database and analyzed with Statistical Package for Social Sciences
      (SPSS). Results. A total of 428 patients with mean age of 8.12 +/- 5.04 SD
      presented for hypospadias repair. Midpenile hypospadias were the most common.
      Chordee, meatal abnormalities, cryptorchidism, and inguinal hernias were observed
      in 74.3%, 9.6%, 2.8%, and 2.1% cases, respectively. Two-stage (Bracka) and TIP
      (tubularized incised urethral plate) repairs were performed in 76.2% and 20.8% of
      cases, respectively. The most common complications were edema and
      urethrocutaneous fistula (UCF). The complications were significantly lower in the
      hands of specialists than residents (P-value = 0.0086). The two-stage hypospadias
      repair resulted in higher complications frequency than single-stage repair (P
      value = 0.0001). Conclusion. Hypospadias surgery has a long learning curve
      because it requires a great deal of temperament, surgical skill and acquaintance
      with magnifications. Single-stage repair should be encouraged wherever applicable
      due to its lower postoperative complications. 

PMID- 24579041
TI  - Point of Care Technologies for HIV.
AB  - Effective prevention of HIV/AIDS requires early diagnosis, initiation of therapy,
      and regular plasma viral load monitoring of the infected individual. In addition,
      incidence estimation using accurate and sensitive assays is needed to facilitate
      HIV prevention efforts in the public health setting. Therefore, more affordable
      and accessible point-of-care (POC) technologies capable of providing early
      diagnosis, HIV viral load measurements, and CD4 counts in settings where HIV is
      most prevalent are needed to enable appropriate intervention strategies and
      ultimately stop transmission of the virus within these populations to achieve the
      future goal of an AIDS-free generation. This review discusses the available and
      emerging POC technologies for future application to these unmet public health
      needs. 

PMID- 24579044
TI  - Effect of Platelet-Rich Plasma (PRP) versus Autologous Whole Blood on Pain and
      Function Improvement in Tennis Elbow: A Randomized Clinical Trial.
AB  - Background. Autologous whole blood and platelet-rich plasma (PRP) have been both
      suggested to treat chronic tennis elbow. The aim of the present study was to
      compare the effects of PRP versus autologous whole blood local injection in
      chronic tennis elbow. Methods. Forty patients with tennis elbow were randomly
      divided into 2 groups. Group 1 was treated with a single injection of 2 mL of
      autologous PRP and group 2 with 2 mL of autologous blood. Tennis elbow strap,
      stretching, and strengthening exercises were administered for both groups during
      a 2-month followup. Pain and functional improvements were assessed using visual
      analog scale (VAS), modified Mayo Clinic performance index for the elbow, and
      pressure pain threshold (PPT) at 0, 4, and 8 weeks. Results. All pain and
      functional variables including VAS, PPT, and Mayo scores improved significantly
      in both groups 4 weeks after injection. No statistically significant difference
      was noted between groups regarding pain scores in 4-week follow-up examination (P
      > 0.05). At 8-week reevaluations, VAS and Mayo scores improved only in PRP group
      (P < 0.05). Conclusion. PRP and autologous whole blood injections are both
      effective to treat chronic lateral epicondylitis. PRP might be slightly superior
      in 8-week followup. However, further studies are suggested to get definite
      conclusion. 

PMID- 24579045
TI  - Pain prevalence and management in an internal medicine setting in Italy.
AB  - Background. Since data on pain evaluation and management in patients admitted to
      internal medicine wards (IMWs) are limited, we aimed to evaluate these aspects in
      a cohort of internistic patients. Methods. We considered all patients
      consecutively admitted from June to December 2011 to our unit. Age, gender, and
      length-of-hospital-stay (LOS) were recorded. Comorbidities were arbitrarily
      defined, and pain severity was evaluated by Numeric Rating Scale (NRS) on
      admission and discharge. Results. The final sample consisted of 526 patients
      (mean age 74 +/- 14 years; 308 women). Significant pain (NRS >= 3) was detected
      in 63% of cases, and severe (NRS >= 7) in 7.6%. Pain was successfully treated,
      and NRS decreased from 4.65 +/- 2.05 to 0.89 +/- 1.3 (P < 0.001). Compared with
      subjects with NRS < 3, those with significant pain were older (75.5 +/- 13.9
      versus 72.9 +/- 14.5 years, P = 0.038), and had a higher LOS (7.9 +/- 6.1 versus
      7.3 +/- 6.8, P = 0.048). Significant pain was independently associated with age
      (OR 0.984, P = 0.018), cancer (OR 3.347, P < 0.001), musculoskeletal disease (OR
      3.054, P < 0.0001), biliary disease (OR 3.100, P < 0.01), and bowel disease (OR
      3.100, P < 0.003). Conclusion. In an internal medicine setting, multiple diseases
      represent significant cause of pain. Prompt pain evaluation and management should
      be performed as soon as possible, in order to avoid patients' suffering and
      reduce the need of hospital stay. 

PMID- 24579046
TI  - The pain frequency-severity-duration scale as a measure of pain: preliminary
      validation in a pediatric chronic pain sample.
AB  - Typically, pain is measured by intensity and sensory characteristics. Although
      intensity is one of the most common dimensions of pain assessment, it has been
      suggested that measuring pain intensity in isolation is only capturing part of
      the pain experience and may not lead to an accurate measurement of how pain
      impacts a child's daily functioning. The current study aimed to develop a measure
      that would capture pain intensity along with frequency and duration in a clinical
      sample of youth diagnosed with chronic pain. The pain-frequency-severity-duration
      (PFSD) scale was developed and data were collected from a multidisciplinary pain
      clinic at a large, midwestern children's hospital. Validated measures of
      functional limitations and health related quality of life were also collected.
      Significant correlations were found between the PFSD composite score, functional
      limitations, and health related quality of life. Future research should continue
      to evaluate this questionnaire utilizing other validated pain measures and other
      areas potentially impacted by chronic pain and with more diverse samples. This
      initial finding suggests that the PFSD is a convenient self-reported measure and
      is strongly related to health related quality of life and functional disability. 

PMID- 24579047
TI  - Parental Catastrophizing Partially Mediates the Association between Parent
      Reported Child Pain Behavior and Parental Protective Responses.
AB  - This study sought to model and test the role of parental catastrophizing in
      relationship to parent-reported child pain behavior and parental protective
      (solicitous) responses to child pain in a sample of children with Inflammatory
      Bowel Disease and their parents (n = 184 dyads). Parents completed measures
      designed to assess cognitions about and responses to their child's abdominal
      pain. They also rated their child's pain behavior. Mediation analyses were
      performed using regression-based techniques and bootstrapping. Results supported
      a model treating parent-reported child pain behavior as the predictor, parental
      catastrophizing as the mediator, and parental protective responses as the
      outcome. Parent-reported child pain behavior predicted parental protective
      responses and this association was mediated by parental catastrophizing about
      child pain: indirect effect (SE) = 2.08 (0.56); 95% CI = 1.09, 3.30. The
      proportion of the total effect mediated was 68%. Findings suggest that
      interventions designed to modify maladaptive parental responses to children's
      pain behaviors should assess, as well as target, parental catastrophizing
      cognitions about their child's pain. 

PMID- 24579048
TI  - Perioperative multimodal anesthesia using regional techniques in the aging
      surgical patient.
AB  - Background. Elderly patients have unique age-related comorbidities that may lead
      to an increase in postoperative complications involving neurological, pulmonary,
      cardiac, and endocrine systems. There has been an increase in the number of
      elderly patients undergoing surgery as this portion of the population is
      increasing in numbers. Despite advances in perioperative anesthesia and analgesia
      along with improved delivery systems, monotherapy with opioids continues to be
      the mainstay for treatment of postop pain. Reliance on only opioids can
      oftentimes lead to inadequate pain control or increase in the incidence of
      adverse events. Multimodal analgesia incorporating regional anesthesia is a
      promising alternative that may reduce needs for high doses and dependence on
      opioids along with any potential associated adverse effects. Methods. The
      following databases were searched for relevant published trials: Cochrane Central
      Register of Controlled Trials and PubMed. Textbooks and meeting supplements were
      also utilized. The authors assessed trial quality and extracted data.
      Conclusions. Multimodal drug therapy and perioperative regional techniques can be
      very effective to perioperative pain management in the elderly. Regional
      anesthesia as part of multimodal perioperative treatment can often reduce
      postoperative neurological, pulmonary, cardiac, and endocrine complications.
      Regional anesthesia/analgesia has not been proven to improve long-term morbidity
      but does benefit immediate postoperative pain control. In addition, multimodal
      drug therapy utilizes a variety of nonopioid analgesic medications in order to
      minimize dosages and adverse effects from opioids while maximizing analgesic
      effect and benefit. 

PMID- 24579050
TI  - Posterior Deep Infiltrating Endometriotic Nodules: Operative Considerations
      according to Lesion Size, Location, and Geometry, during One's Learning Curve.
AB  - We conducted this prospective cohort study to standardize our laparoscopic
      technique of excision of posterior deep infiltrating endometriosis (DIE) nodules,
      according to their size, location, and geometry, including 36 patients who were
      grouped, according to principal pelvic expansion of the nodule, into groups with
      central (group 1) and lateral (group 2) lesions, and according to nodule size,
      into <=2 cm (group A) and >2 cm (group B) lesions, respectively. In cases of
      group 1 the following operative steps were more frequently performed compared to
      those of group 2: suspension of the rectosigmoid, colpectomy, and placement of
      bowel wall reinforcement sutures. The opposite was true regarding suspension of
      the adnexa, systematic ureteric dissection, and removal of the diseased pelvic
      peritoneum. When grouping patients according to nodule size, almost all of the
      examined parameters were more frequently applied to patients of group B: adnexal
      suspension, suspension of the rectosigmoid, systematic ureteric dissection,
      division of uterine vein, colpectomy, and placement of bowel wall reinforcement
      sutures. Nodule size was the single most important determinant of duration of
      surgery. In conclusion, during the building-up of one's learning curve of
      laparoscopic excision of posterior DIE nodules, technique standardization is very
      important to avoid complications. 

PMID- 24579052
TI  - Use of flattening filter-free photon beams in treating medulloblastoma: a
      dosimetric evaluation.
AB  - Aim. To evaluate the dosimetric benefits of flattening filter-free (FFF) photon
      beams in intensity modulated radiation therapy (IMRT) and Rapid Arc (RA) over
      conventional CSI methods. Methods and Materials. Five patients treated with IMRT
      using static multileaf collimators (MLC) were randomly selected for this
      retrospective study. Dynamic MLC IMRT, RA, and conformal therapy (3DCRT) were
      iterated with the same CT data sets with and without flattening filter photons.
      Total dose prescribed was 28.80 Gy in 16 fractions. Dosimetric parameters such as
      D max?, D min?, D mean, V 95%, V 107%, DHI, and CI for PTV and D max?, D mean, V
      80%, V 50%, V 30%, and V 10% for OARs were extracted from DVHs. Beam on time
      (BOT) for various plans was also compared. Results. FFF RA therapy (6F_RA)
      resulted in highly homogeneous and conformal doses throughout the craniospinal
      axis. 3DCRT resulted in the highest V 107% (SD) 46.97 +/- 28.6, whereas
      flattening filter (FF) and FFF dynamic IMRT had a minimum V 107%. 6F_RA and
      6F_DMLC resulted in lesser doses to thyroid, eyes, esophagus, liver, lungs, and
      kidneys. Conclusion. FFF IMRT and FFF RA for CSI have definite dosimetric
      advantages over 3DCRT technique in terms of target coverage and OAR sparing. Use
      of FFF in IMRT resulted in 50% reduction in BOT, thereby increasing the treatment
      efficiency. 

PMID- 24579049
TI  - Oral postdialysis cholecalciferol supplementation in patients on maintenance
      hemodialysis: a dose-response approach.
AB  - The aim of the present study was to evaluate the dose of postdialysis
      cholecalciferol needed to maintain the 25-hydroxyvitamin D [25(OH)D] levels in
      the optimal range of 75-150 nmol/L. Twenty-six patients who had low baseline
      25(OH)D levels (mean 27.5 +/- 14.9 nmol/L) were studied. The 25(OH)D levels were
      measured every 2 months for one year. During the first two months, all the
      patients received 2000 IU of cholecalciferol after each hemodialysis (=6000
      IU/wk). Thereafter, the dose was individualized and adapted every 2 months by
      administering 1 to 6 cholecalciferol tablets (2000 IU each) per week (total
      weekly dose = 2000-12000 IU/wk). During cholecalciferol supplementation, the
      25(OH)D concentrations rapidly increased from baseline to 140.1 +/- 28.3 nmol/L
      at month 6 and 95.6 +/- 20.9 nmol/L at month 12. At month twelve, 86% of the
      patients had 25(OH)D levels within the target range with a mean dose of 5917 +/-
      4106 IU/wk of cholecalciferol; however, the amount needed to maintain these
      levels varied widely from 0 (n = 2) to 12000 IU/wk (n = 5). In conclusion,
      postdialysis cholecalciferol prescription is quite effective in correcting
      vitamin D deficiency/insufficiency, but the amount of cholecalciferol needed to
      maintain the 25(OH)D levels within the optimal range over the long-term varies
      widely among patients and must be individualized. 

PMID- 24579053
TI  - Mini-arc for the treatment of female stress urinary incontinence: long-term
      prospective evaluation by patient reported outcomes.
AB  - Single-incision slings were introduced in the surgical treatment of female stress
      urinary incontinence (SUI) to lessen the morbidity associated with traditional
      midurethral slings. However, long-term reports on patient satisfaction are still
      scarce. This study describes the outcome of women treated with Mini-Arc at a mean
      follow-up of 45 months. In a previous report on 105 women with 15-month mean
      follow-up, 84 (80%) were found cured and 12 (11%) improved. Now, with a mean
      follow-up of 45 months, cured/improved patients were reassessed by telephone and
      completed Patient Global Impression of Improvement (PGI-I), Patient Global
      Impression of Severity (PGI-S), rated their improvement in a 0-100 scale, and
      answered if they would recommend the procedure. At 45-month follow-up, 73 women
      cured/improved were available for evaluation. Over 80% of the cured patients
      rated the improvement of SUI by the PGI-I as "very much better" or "much better,"
      reported their urinary tract condition to be "normal" on PGI-S, and described
      their improvement >70%. Ninety percent would recommend this procedure to a
      friend. The improved-patient population is very small (n = 7). This study shows
      that the majority of patients cured/improved after Mini-Arc placement maintain a
      high degree of satisfaction at a long-term evaluation. 

PMID- 24579054
TI  - Surgical treatment of osteopetrosis-related femoral fractures: two case reports
      and literature review.
AB  - Osteopetrosis is a rare hereditary disease which is characterized by increased
      bone density. Bone resorption is insufficient or fails due to the osteoclast
      defect in osteopetrosis. Half of the patients are asymptomatic and diagnosed
      incidentally or based on the presence of fracture. Adult onset osteopetrosis
      usually presents with hip and proximal femoral fractures. Internal fixation can
      be performed; however, technical challenges may be experienced due to increased
      bone density. As in other fractures, nonunion or varus malunion of these
      fractures may occur. Although rare, osteopetrosis may complicate treatment of
      fractures in such patients. In this study, we aimed to present two new cases of
      ADO type II with an osteopetrotic femoral fracture along with the clinical and
      radiological findings in the light of a comprehensive literature review.
      Orthopaedics surgeons should be aware of intraoperative technical difficulties
      and possible postoperative complications during the follow-up period.
      Investigation would be beneficial for the diagnosis of osteopetrosis such the
      patient with fractures who has minor trauma history and increased bone density in
      radiography. 

PMID- 24579055
TI  - Clinical feature of intrahepatic B-lymphocytes in chronic hepatitis B.
AB  - Humoral immunity constitutes major defense mechanism against viral infections.
      However, the association of hepatic injury and B-cells population in chronic
      hepatitis B virus (HBV) carriers has not been studied well. In this study, fifty
      seven hepatitis B surface antigen (HBsAg) positive and HBeAg negative patients
      were studied to determine the expression of CD20, a cell surface marker expressed
      on B-cells, in liver biopsy sections using immunohistochemistry. The patients'
      clinical data at the time of liver biopsy were acquired from their medical
      records. There was a significant association between log HBV DNA and both ALT (r
      = 0.36, P = 0.006) and histologic activity index (HAI) total score (r = 0.3, P =
      0.02), respectively. The CD20 was expressed in all 57 liver biopsy samples with a
      submembranous and membranous staining pattern and its expression was
      significantly associated with HAI total score (r = 0.32, P = 0.01) and stage of
      fibrosis (r = 0.31, P = 0.02). The susceptible B lymphocytes to hepatitis B virus
      might be implicated in the development of immune mediated inflammation of HBV
      induced hepatic injury. The present data also support that the liver is
      potentially one of the secondary lymphoid organs. 

PMID- 24579051
TI  - Neuroprotection in stroke: past, present, and future.
AB  - Stroke is a devastating medical condition, killing millions of people each year
      and causing serious injury to many more. Despite advances in treatment, there is
      still little that can be done to prevent stroke-related brain damage. The concept
      of neuroprotection is a source of considerable interest in the search for novel
      therapies that have the potential to preserve brain tissue and improve overall
      outcome. Key points of intervention have been identified in many of the processes
      that are the source of damage to the brain after stroke, and numerous treatment
      strategies designed to exploit them have been developed. In this review,
      potential targets of neuroprotection in stroke are discussed, as well as the
      various treatments that have been targeted against them. In addition, a summary
      of recent progress in clinical trials of neuroprotective agents in stroke is
      provided. 

PMID- 24579056
TI  - Parecoxib reduces systemic inflammation and acute lung injury in burned animals
      with delayed fluid resuscitation.
AB  - Burn injuries result in the release of proinflammatory mediators causing both
      local and systemic inflammation. Multiple organ dysfunctions secondary to
      systemic inflammation after severe burn contribute to adverse outcome, with the
      lungs being the first organ to fail. In this study, we evaluate the anti
      inflammatory effects of Parecoxib, a parenteral COX-2 inhibitor, in a delayed
      fluid resuscitation burned rat model. Anaesthetized Sprague Dawley rats were
      inflicted with 45% total body surface area full-thickness scald burns and
      subsequently subjected to delayed resuscitation with Hartmann's solution.
      Parecoxib (0.1, 1.0, and 10 mg/kg) was delivered intramuscularly 20 min after
      injury followed by 12 h interval and the rats were sacrificed at 6 h, 24 h, and
      48 h. Burn rats developed elevated blood cytokines, transaminase, creatinine, and
      increased lung MPO levels. Animals treated with 1 mg/kg Parecoxib showed
      significantly reduced plasma level of CINC-1, IL-6, PGEM, and lung MPO. Treatment
      of 1 mg/kg Parecoxib is shown to mitigate systemic and lung inflammation without
      significantly affecting other organs. At present, no specific therapeutic agent
      is available to attenuate the systemic inflammatory response secondary to burn
      injury. The results suggest that Parecoxib may have the potential to be used both
      as an analgesic and ameliorate the effects of lung injury following burn. 

PMID- 24579058
TI  - Virtual Reality for Sensorimotor Rehabilitation Post-Stroke: The Promise and
      Current State of the Field.
AB  - Developments over the past 2 years in virtual reality (VR) augmented sensorimotor
      rehabilitation of upper limb use and gait post-stroke were reviewed. Studies were
      included if they evaluated comparative efficacy between VR and standard of care,
      and or differences in VR delivery methods; and were CEBM (center for evidence
      based medicine) level 2 or higher. Eight upper limb and two gait studies were
      included and described using the following categories hardware (input and
      output), software (virtual task and feedback and presentation) intervention
      (progression and dose), and outcomes. Trends in the field were commented on, gaps
      in knowledge identified, and areas of future research and translation of VR to
      practice were suggested.

PMID- 24579057
TI  - Bacterial ice crystal controlling proteins.
AB  - Across the world, many ice active bacteria utilize ice crystal controlling
      proteins for aid in freezing tolerance at subzero temperatures. Ice crystal
      controlling proteins include both antifreeze and ice nucleation proteins.
      Antifreeze proteins minimize freezing damage by inhibiting growth of large ice
      crystals, while ice nucleation proteins induce formation of embryonic ice
      crystals. Although both protein classes have differing functions, these proteins
      use the same ice binding mechanisms. Rather than direct binding, it is probable
      that these protein classes create an ice surface prior to ice crystal surface
      adsorption. Function is differentiated by molecular size of the protein. This
      paper reviews the similar and different aspects of bacterial antifreeze and ice
      nucleation proteins, the role of these proteins in freezing tolerance, prevalence
      of these proteins in psychrophiles, and current mechanisms of protein-ice
      interactions. 

PMID- 24579059
TI  - Endophthalmitis Associated with Intravitreal Anti-Vascular Endothelial Growth
      Factor Injections.
AB  - The use of anti-vascular endothelial growth factor (VEGF) agents has led to a
      dramatic increase in the number of intravitreal injections. Endophthalmitis
      remains a rare but potentially vision-threatening complication of intravitreal
      injections. Recent large series have estimated this risk to be about one in 3,000
      injections or less. Bevacizumab, which is generally prepared by a compounding
      pharmacy, is associated with additional risks of contamination. Although
      endophthalmitis cannot be prevented in all cases, certain risk reduction
      strategies have been proposed, including the use of an eyelid speculum, povidone
      iodine, avoidance of needle contact with the eyelid margin or eyelashes, and
      avoidance of routine post-injection antibiotics. Despite these precautions, some
      patients will develop endophthalmitis following intravitreal anti-VEGF
      injections, and outcomes may be poor despite prompt and appropriate therapy.

PMID- 24579060
TI  - The Outcomes of Living Kidney Donation from Medically Complex Donors:
      Implications for the Donor and the Recipient.
AB  - Living kidney donation is an important option for patients with end-stage renal
      disease (ESRD), and has improved life expectancy and quality for patients
      otherwise requiring maintenance dialysis or deceased-donor transplantation. Given
      the favorable outcomes of live donation and the shortage of organs to transplant,
      individuals with potentially unfavorable demographic and clinical characteristics
      are increasingly being permitted to donate kidneys. While this trend has
      successfully expanded the live donor pool, it has raised concerns as to which
      acceptance criteria are safe. This review aims to summarize the existing
      literature on the outcomes of transplantation from medically complex, living
      kidney donors, including both donor and recipient outcomes when available.

PMID- 24579061
TI  - Investigation of the far-field approximation for modeling a transducer's spatial
      impulse response in photoacoustic computed tomography.
AB  - When ultrasonic transducers with large detecting areas and/or compact measurement
      geometries are employed in photoacoustic computed tomography (PACT), the spatial
      resolution of reconstructed images can be significantly degraded. Our goal in
      this work is to clarify the domain of validity of an imaging model that mitigates
      such effects by use of a far-field approximation. Computer-simulation studies are
      described that demonstrate the far-field-based imaging model is highly accurate
      for a practical 3D PACT imaging geometry employed in an existing small animal
      imaging system. For use in special cases where the far-field approximation is
      violated, an extension of the far-field-based imaging model is proposed that
      divides the transducer face into a small number of rectangular patches that are
      each described accurately by use of the far-field approximation.

PMID- 24579062
TI  - Preoperative prediction of type 2 diabetes remission after Roux-en-Y gastric
      bypass surgery: a retrospective cohort study.
AB  - BACKGROUND: About 60% of patients with type 2 diabetes achieve remission after
      Roux-en-Y gastric bypass (RYGB) surgery. No accurate method is available to
      preoperatively predict the probability of remission. Our goal was to develop a
      way to predict probability of diabetes remission after RYGB surgery on the basis
      of preoperative clinical criteria. METHODS: In a retrospective cohort study, we
      identified individuals with type 2 diabetes for whom electronic medical records
      were available from a primary cohort of 2300 patients who underwent RYGB surgery
      at the Geisinger Health System (Danville, PA, USA) between Jan 1, 2004, and Feb
      15, 2011. Partial and complete remission were defined according to the American
      Diabetes Association criteria. We examined 259 clinical variables for our
      algorithm and used multiple logistic regression models to identify independent
      predictors of early remission (beginning within first 2 months after surgery and
      lasting at least 12 months) or late remission (beginning more than 2 months after
      surgery and lasting at least 12 months). We assessed a final Cox regression model
      with a consistent subset of variables that predicted remission, and used the
      resulting hazard ratios (HRs) to guide creation of a weighting system to produce
      a score (DiaRem) to predict probability of diabetes remission within 5 years. We
      assessed the validity of the DiaRem score with data from two additional cohorts.
      FINDINGS: Electronic medical records were available for 690 patients in the
      primary cohort, of whom 463 (63%) had achieved partial or complete remission.
      Four preoperative clinical variables were included in the final Cox regression
      model: insulin use, age, HbA1c concentration, and type of antidiabetic drugs. We
      developed a DiaRem score that ranges from 0 to 22, with the greatest weight given
      to insulin use before surgery (adding ten to the score; HR 5.90, 95% CI 4.41
      7.90; p<0.0001). Kaplan-Meier analysis showed that 88% (95% CI 83-92%) of
      patients who scored 0-2, 64% (58-71%) of those who scored 3-7, 23% (13-33%) of
      those who scored 8-12, 11% (6-16%) of those who scored 13-17, and 2% (0-5%) of
      those who scored 18-22 achieved early remission (partial or complete). As in the
      primary cohort, the proportion of patients achieving remission in the replication
      cohorts was highest for the lowest scores, and lowest for the highest scores.
      INTERPRETATION: The DiaRem score is a novel preoperative method to predict the
      probability of remission of type 2 diabetes after RYGB surgery. FUNDING:
      Geisinger Health System and the US National Institutes of Health.

PMID- 24579063
TI  - Effect of universal MODS access on pulmonary tuberculosis treatment outcomes in
      new patients in Peru.
AB  - SETTING: Primary health care centres in Callao, Peru. OBJECTIVES: To evaluate the
      effect of universal access to the microscopic-observation drug susceptibility
      (MODS) assay on treatment outcomes in new and primary multidrug-resistant
      tuberculosis (MDR-TB) patients and on the process of drug susceptibility testing
      (DST). DESIGN: Retrospective review of tuberculosis (TB) registers and clinical
      records before (2007) and after (2009) the introduction of MODS in 2008. RESULTS:
      There were 281 patients in each cohort. Favourable treatment outcomes for 2007
      (81%) and 2009 (77%) cohorts were similar. There was an increase in loss to
      follow-up (from 6% to 10%, P = 0.04) and a reduction in failure rates (from 4% to
      0.4%, P = 0.01) in the 2009 compared with the 2007 cohort. In new MDR-TB cases (n
      = 22), a favourable treatment outcome was improved (from 46% to 82%, P = 0.183)
      in the 2009 cohort. DST coverage improved (from 24% to 74%, P < 0.001), and a
      significant reduction in time to diagnosis of drug-susceptible (from 118 to 33
      days, P < 0.001) and MDR-TB (from 158 to 52 days, P =30.003) was observed in the
      2009 cohort. CONCLUSION: Universal access to MODS increased DST coverage, reduced
      the time required to obtain DST results and was associated with reduced failure
      rates. MODS can make an important contribution to TB management and control in
      Peru.

PMID- 24579064
TI  - BRCA 1/2-Mutation Related and Sporadic Breast and Ovarian Cancers: More Alike
      than Different.
AB  - No longer is histology solely predictive of cancer treatment and outcome. There
      is an increasing influence of tumor genomic characteristics on therapeutic
      options. Both breast and ovarian cancers are at higher risk of development in
      patients with BRCA 1/2-germline mutations. Recent data from The Cancer Genome
      Atlas and others have shown a number of genomic similarities between triple
      negative breast cancers (TNBCs) and ovarian cancers. Recently, poly (ADP-ribose)
      polymerase (PARP) inhibitors have shown promising activity in hereditary BRCA 1/2
      mutated and sporadic breast and ovarian cancers. In this review, we will
      summarize the current literature regarding the genomic and phenotypic
      similarities between BRCA 1/2-mutation related cancers, sporadic TNBCs, and
      sporadic ovarian cancers. We will also review Phase I, II, and III data using
      PARP inhibitors for these malignancies and compare and contrast the results with
      respect to histology. 

PMID- 24579065
TI  - Radioembolization and the Dynamic Role of (90)Y PET/CT.
AB  - Before the advent of tomographic imaging, it was postulated that decay of (90) Y
      to the 0(+) excited state of (90)Zr may result in emission of a positron-electron
      pair. While the branching ratio for pair-production is small (~32 * 10(-6)), PET
      has been successfully used to image (90) Y in numerous recent patients and
      phantom studies. (90) Y PET imaging has been performed on a variety of PET/CT
      systems, with and without time-of-flight (TOF) and/or resolution recovery
      capabilities as well as on both bismuth-germanate and lutetium yttrium
      orthosilicate (LYSO)-based scanners. On all systems, resolution and contrast
      superior to bremsstrahlung SPECT has been reported. The intrinsic radioactivity
      present in LYSO-based PET scanners is a potential limitation associated with
      accurate quantification of (90) Y. However, intrinsic radioactivity has been
      shown to have a negligible effect at the high activity concentrations common in
      (90) Y radioembolization. Accurate quantification is possible on a variety of PET
      scanner models, with or without TOF, although TOF improves accuracy at lower
      activity concentrations. Quantitative (90) Y PET images can be transformed into 3
      dimensional (3D) maps of absorbed dose based on the premise that the (90) Y
      activity distribution does not change after infusion. This transformation has
      been accomplished in several ways, although the most common is with the use of 3D
      dose-point-kernel convolution. From a clinical standpoint, (90) Y PET provides a
      superior post-infusion evaluation of treatment technical success owing to its
      improved resolution. Absorbed dose maps generated from quantitative PET data can
      be used to predict treatment efficacy and manage patient follow-up. For patients
      who receive multiple treatments, this information can also be used to provide
      patient-specific treatment-planning for successive therapies, potentially
      improving response. The broad utilization of (90) Y PET has the potential to
      provide a wealth of dose-response information, which may lead to development of
      improved radioembolization treatment-planning models in the future. 

PMID- 24579066
TI  - Bis-indolic compounds as potential new therapeutic alternatives for tularaemia.
AB  - Francisella tularensis is the etiological agent of tularaemia and a CDC class A
      biological threat agent. Few antibiotic classes are currently useful in treating
      tularaemia, including the aminoglycosides gentamicin and streptomycin,
      fluoroquinolones, and tetracyclines. However, treatment failures and relapses
      remain frequent and F. tularensis strains resistant to antibiotics have been
      easily selected in vitro. In this study, we evaluated the activity of new
      synthetic bis-indole derivatives against this pathogen. Minimum inhibitory
      concentrations (MICs) of four compounds (dcm01 to dcm04) were determined for the
      reference strains F. tularensis subsp. holarctica LVS NCTC10857, F. tularensis
      subsp. novicida CIP56.12 and F. philomiragia ATCC25015, and for 41 clinical
      strains of F. tularensis subsp. holarctica isolated in France. Minimal
      bactericidal concentrations (MBCs) were determined for the dcm02 and dcm04
      compounds for the LVS and two clinical strains. Killing curves were also
      determined for the same three strains exposed to dcm04. All tested bis-indole
      compounds were bacteriostatic against F. tularensis subsp. holarctica strains,
      with a MIC90 of 8 MUg/mL for dcm01, dcm02, and dcm03, and 2 MUg/mL for dcm04.
      Only one strain was resistant to both dcm01 and dcm03, with MICs > 32 MUg/mL. In
      contrast, F. tularensis subsp. novicida was resistant to all derivatives and F.
      philomiragia was only susceptible to dcm02 and dcm04, with MICs of 16 and 4
      MUg/mL, respectively. MBC and killing curve experiments revealed significant
      bactericidal activity (i.e., 3-log reduction of the bacterial inoculum) of the
      dcm02 and dcm04 compounds only for the LVS strain. In conclusion, we have
      identified novel synthetic bis-indole compounds that are active against F.
      tularensis subsp. holarctica. They may be drug candidates for the development of
      new therapeutic alternatives for tularaemia treatment. Their further
      characterization is needed, especially identification of their bacterial targets.

PMID- 24579067
TI  - Unilateral peripheral neuropathic pain: The role of neurodiagnostic skin biopsy.
AB  - According to the current definition of neuropathic pain ("pain arising as a
      direct consequence of a lesion or disease affecting the somatosensory system"),
      the demonstration of a lesion or disease involving the somatosensory system is
      mandatory for the diagnosis of definite neuropathic pain. Although several
      methods are currently available for this aim, none is suitable for every type of
      disease (or lesion). Neurodiagnostic skin biopsy (NSB) is a relatively new
      technique for the diagnosis of peripheral nerve lesions. It is an objective
      method, completely independent from the patient's complaining, based on
      immunohistochemical staining techniques that allow measurement of the density of
      the epidermal nerve fibers, currently considered the free nerve endings of small
      diameter (A-delta and C) afferent fibers. NSB has the important property of being
      used to investigate the skin, allowing obtaining a diagnosis of small fiber
      axonal neuropathy of peripheral nerves supplying every body part covered by skin.
      This feature appears to be very important, particularly in cases of unilateral
      nerve lesions, because it allows going beyond the possibilities of
      neurophysiological tests which are available only for a limited number of
      peripheral nerves. All these characteristics make NSB a precious instrument for
      the diagnosis of peripheral unilateral neuropathic pain. 

PMID- 24579068
TI  - Surgical removal of a large mobile left ventricular thrombus via left atriotomy.
AB  - Left ventricular (LV) thrombus is a life-threatening complication of severe LV
      dysfunction. Ventriculotomy has been a commonly performed procedure for LV
      thrombus; however, it often further decrease LV function after surgery. We
      present an alternative approach to thrombectomy in order to minimize the
      postoperative LV dysfunction. A 37-year-old female with a postpartum
      cardiomyopathy found to have poor LV function and a large left ventricular apical
      thrombus (3 cm * 3 cm) attached to the apex by a narrow stalk. Given her severe
      LV dysfunction, the LV thrombus was approached via left atriotomy under
      cardiopulmonary bypass. The LV thrombus was easily extracted with gentle traction
      via the mitral valve. Postoperatively, the patient was discharged home without
      any embolization event or inotropic support. LV thrombectomy via left atriotomy
      through the mitral valve could be an alternative option for the patients with
      poor LV function with a mobile LV thrombus. 

PMID- 24579069
TI  - Unexpected anomaly of the common bile duct and pancreatic duct.
AB  - Variations in the bile duct and pancreatic duct opening are related to the
      process of rotation and recanalization during embryologic development. Complete
      non-union of distal common bile duct and pancreatic duct gives rise to double
      papillae of Vater. The separation of the drainage of the main pancreatic duct and
      bile duct can be appreciated by careful assessment at the time of endoscopic
      retrograde cholangiopancreatograpy. The cranial orifice is a bile duct opening,
      whereas the caudal orifice is a pancreatic duct opening. The separate orifice
      finding can be confirmed by cholangiogram and pancreatogram with no communication
      between the two orifices. Endoscopists should be aware of this rare variant
      because late recognition can result in unnecessary manipulation and contrast
      injections of the main pancreatic duct and biliary cannulation failure. 

PMID- 24579070
TI  - Severe isolated sciatic neuropathy due to a modified lotus position.
AB  - A 51-year-old man presented to our hospital with progressive pain and weakness in
      his right leg. Neurological examination revealed atrophy of all muscles of the
      right leg, unilateral foot drop and paralysis of the anterior tibial and
      gastrocnemicus muscles. Electromyography confirmed a severe isolated sciatic
      neuropathy in the thigh. For unclear reasons, our patient habitually used to sit
      in a modified lotus position. We concluded that this position, in literature
      known as "lotus neuropathy" had resulted in the sciatic neuropathy. After more
      than a year our patient was referred again to our outpatient clinic. At that time
      there was only minimal improvement, now with an achilles tendon contracture and
      pes equinus due to immobility. 

PMID- 24579071
TI  - Utility of diffusion-weighted imaging in the diagnosis of inguinal lymph node
      metastasis with malignant melanoma.
AB  - Malignant melanoma is a malignancy of pigment-producing cells (melanocytes)
      located predominantly in the skin. Nodal metastases are an adverse prognostic
      factor compromising long term patient survival. Therefore, accurate detection of
      regional nodal metastases is required for optimization of treatment. Computed
      tomography (CT) and magnetic resonance imaging (MRI) remain the primary imaging
      modalities for regional staging of malignant melanoma. However, both modalities
      rely on size-related and morphological criteria to differentiate between benign
      and malignant lymph nodes, decreasing the sensitivity for detection of small
      metastases. Surgery is the primary mode of therapy for localized cutaneous
      melanoma. Patients should be followed up for metastases after surgical removal.
      We report here a case of inguinal lymph node enlargement with a genital vesicular
      lesion with a history of surgery for malignant melanoma on her thigh two years
      ago. CT and diffusion weighted-MRI (DW-MRI) were applied for the lymph node
      identification. DW-MRI revealed malignant lymph nodes due to malignant melanoma
      metastases correlation with pathological findings. 

PMID- 24579072
TI  - Baastrup's disease: The kissing spine.
AB  - A 67-year-old male presented with a gradually progressive low back pain of 2
      years duration. The patient was leading a retired life and there was no history
      of chronic fever or significant trauma. There was no radiation of pain or any
      features suggestive of claudication. There was no history of any comorbidity. The
      pain was aggravated with extension of the spine and relieved with flexion. There
      was no swelling or neurological deficit, but muscle spasm was present.
      Radiographs of the spine revealed degenerative changes in the lumbosacral spine,
      along with articulation of spinous processes at in lumbar spine at all levels
      level suggestive of Baastrup's disease, commonly known as "kissing spine".
      Routine blood investigations were within normal limits. The patient was managed
      conservatively. He was given a week's course of analgesics and muscle relaxants
      and then started on spinal flexion exercises, with significant improvement being
      noted at 6 months follow up. 

PMID- 24579073
TI  - Ameloblastic carcinoma: Report of a rare case.
AB  - Ameloblastic carcinoma is a rare odontogenic tumor exhibiting histological
      evidence of malignancy in the primary or recurrent tumor. It is characterized by
      rapid, painful expansion of the jaw, unlike conventional ameloblastomas. The
      tumor most frequently involves the mandible. The expanding lesion causes
      perforation of the buccal and lingual plates of the jaw and invades the
      surrounding soft tissue. Rapidly growing large tumor mass may cause tooth
      mobility. A mandibular tumor involving the mental nerve leads to paresthesia of
      the nerve. A maxillary tumor can produce a fistula in the palate and paresthesia
      of the infraorbital nerve. Most ameloblastic carcinomas are presumed to have
      arisen de novo with a few cases of malignant transformation of ameloblastomas.
      Although rare, these lesions have been known to metastasize, mostly to the
      regional lymph nodes or lungs. A case of ameloblastic carcinoma in a 60-year-old
      man is reported here and its clinical, radiological and histological features are
      discussed. 

PMID- 24579074
TI  - PHBV/PAM scaffolds with local oriented structure through UV polymerization for
      tissue engineering.
AB  - Locally oriented tissue engineering scaffolds can provoke cellular orientation
      and direct cell spread and migration, offering an exciting potential way for the
      regeneration of the complex tissue. Poly(3-hydroxybutyrate-co-3-hydroxyvalerate)
      (PHBV) scaffolds with locally oriented hydrophilic polyacrylamide (PAM) inside
      the macropores of the scaffolds were achieved through UV graft polymerization.
      The interpenetrating PAM chains enabled good interconnectivity of PHBV/PAM
      scaffolds that presented a lower porosity and minor diameter of pores than PHBV
      scaffolds. The pores with diameter below 100  MUm increased to 82.15% of PHBV/PAM
      scaffolds compared with 31.5% of PHBV scaffolds. PHBV/PAM scaffold showed a much
      higher compressive elastic modulus than PHBV scaffold due to PAM stuffing. At 5
      days of culturing, sheep chondrocytes spread along the similar direction in the
      macropores of PHBV/PAM scaffolds. The locally oriented PAM chains might guide the
      attachment and spreading of chondrocytes and direct the formation of
      microfilaments via contact guidance.

PMID- 24579075
TI  - Long-term use of probiotics Lactobacillus and Bifidobacterium has a prophylactic
      effect on the occurrence and severity of pouchitis: a randomized prospective
      study.
AB  - AIM: The aim of the study was to assess the impact of the long-term use of the
      composite probiotics in patients after restorative proctocolectomy. METHOD: Forty
      three patients (20 females and 23 males, aged 21 to 68 years) after restorative
      proctocolectomy were included in the study. After randomization patients were
      divided into placebo group and treatment group with oral intake of probiotic
      containing Lactobacillus acidophilus, Lactobacillus delbrueckii subsp.
      bulgaricus, and Bifidobacterium bifidus. Patients were investigated during
      initial visit and during final visit after 9 months. All patients were subjected
      to standard clinical and endoscopic examination with microscopic study of the
      specimens. Concentrations of calprotectin and pyruvate kinase isoenzyme M2-PK
      were determined in all cases. RESULTS: The average severity of pouchitis and the
      number of patients with pouchitis significantly decrease after 9 months of the
      probiotic taking. The concentrations of calprotectin and pyruvate kinase
      isoenzyme M2-PK significantly decreased after the therapy. CONCLUSIONS: Nine
      months of the probiotic treatment (Lactobacillus acidophilus, Lactobacillus
      delbrueckii subsp. bulgaricus, and Bifidobacterium bifidus) reduced the number of
      patients with pouchitis, decreased the PDAI score, and also decreased the fecal
      pyruvate kinase and calprotectin. The long-term probiotics use is safe and well
      accepted and can be an effective method of the pouchitis prevention.

PMID- 24579076
TI  - Biochemical and anatomical changes and yield reduction in rice (Oryza sativa L.)
      under varied salinity regimes.
AB  - Five Malaysian rice (Oryza sativa L.) varieties, MR33, MR52, MR211, MR219, and
      MR232, were tested in pot culture under different salinity regimes for
      biochemical response, physiological activity, and grain yield. Three different
      levels of salt stresses, namely, 4, 8, and 12 dS m(-1), were used in a randomized
      complete block design with four replications under glass house conditions. The
      results revealed that the chlorophyll content, proline, sugar content, soluble
      protein, free amino acid, and yield per plant of all the genotypes were
      influenced by different salinity levels. The chlorophyll content was observed to
      decrease with salinity level but the proline increased with salinity levels in
      all varieties. Reducing sugar and total sugar increased up to 8 dS m(-1) and
      decreased up to 12 dS m(-1). Nonreducing sugar decreased with increasing the
      salinity levels in all varieties. Soluble protein and free amino acid also
      decreased with increasing salinity levels. Cortical cells of MR211 and MR232 did
      not show cell collapse up to 8 dS m(-1) salinity levels compared to susceptible
      checks (IR20 and BRRI dhan29). Therefore, considering all parameters, MR211 and
      MR232 showed better salinity tolerance among the tested varieties. Both cluster
      and principal component analyses depict the similar results. 

PMID- 24579077
TI  - Chemical synthesis, characterisation, and biocompatibility of nanometre scale
      porous anodic aluminium oxide membranes for use as a cell culture substrate for
      the vero cell line: a preliminary study.
AB  - In this preliminary study we investigate for the first time the biomedical
      potential of using porous anodic aluminium oxide (AAO) membranes as a cell
      substrate for culturing the Cercopithecus aethiops (African green monkey) Kidney
      (Vero) epithelial cell line. One advantage of using the inorganic AAO membrane is
      the presence of nanometre scale pore channels that allow the exchange of
      molecules and nutrients across the membrane. The size of the pore channels can be
      preselected by adjusting the controlling parameters of a temperature controlled
      two-step anodization process. The cellular interaction and response of the Vero
      cell line with an in-house synthesised AAO membrane, a commercially available
      membrane, and a glass control were assessed by investigating cell adhesion,
      morphology, and proliferation over a 72 h period. The number of viable cells
      proliferating over the respective membrane surfaces revealed that the locally
      produced in-house AAO membrane had cells numbers similar to the glass control.
      The study revealed evidence of focal adhesion sites over the surface of the
      nanoporous membranes and the penetration of cellular extensions into the pore
      structure as well. The outcome of the study has revealed that nanometre scale
      porous AAO membranes have the potential to become practical cell culture scaffold
      substrates with the capability to enhance adhesion and proliferation of Vero
      cells. 

PMID- 24579078
TI  - Evaluation of antioxidant compounds, antioxidant activities, and mineral
      composition of 13 collected purslane (Portulaca oleracea L.) accessions.
AB  - The methanolic extracts of 13 accessions of purslane were analyzed for their
      total phenol content (TPC), total flavonoid contents (TFC), and total carotenoid
      contents (TCC) and antioxidant activity of extracts was screened using FRAP assay
      and DPPH radical scavenging methods. The TPC, TFC, and TCC ranged from 0.96 +/-
      0.04 to 9.12 +/- 0.29 mg GAE/g DW, 0.13 +/- 0.04 to 1.44 +/- 0.08 mg RE/g DW, and
      0.52 +/- 0.06 to 5.64 +/- 0.09 mg (beta-carotene equivalent) BCE/g DW,
      respectively. The DPPH scavenging (IC50) activity varied between 2.52 +/- 0.03
      mg/mL and 3.29 +/- 0.01 mg/mL and FRAP ranged from 7.39 +/- 0.08 to 104.2 +/-
      6.34  MUmol TE/g DW. Among all the measured micro- and macrominerals K content
      was the highest followed by N, Na, Ca, Mg, P, Fe, Zn, and Mn. The overall
      findings proved that ornamental purslane was richer in antioxidant properties,
      whereas common purslane possesses more mineral contents than ornamental ones.

PMID- 24579079
TI  - Microtexturing of the conductive PEDOT:PSS polymer for superhydrophobic organic
      electrochemical transistors.
AB  - Superhydrophobic surfaces are bioinspired, nanotechnology artifacts, which
      feature a reduced friction coefficient, whereby they can be used for a number of
      very practical applications including, on the medical side, the manipulation of
      biological solutions. In this work, we integrated superhydrophobic patterns with
      the conducting polymer PEDOT:PSS, one of the most used polymers in organic
      electronics because highly sensitive to ionized species in solution. In doing so,
      we combined geometry and materials science to obtain an advanced device where, on
      account of the superhydrophobicity of the system, the solutions of interest can
      be manipulated and, on account of the conductive PEDOT:PSS polymer, the charged
      molecules dispersed inside can be quantitatively measured. This original
      substrate preparation allowed to perform electrochemical measurements on ionized
      species in solution with decreasing concentration down to 10(-7) molar. Moreover,
      it was demonstrated the ability of the device of realizing specific, combined
      time and space resolved analysis of the sample. Collectively, these results
      demonstrate how a tight, interweaving integration of different disciplines can
      provide realistic tools for the detection of pathologies. The scheme here
      introduced offers breakthrough capabilities that are expected to radically
      improve both the pace and the productivity of biomedical research, creating an
      access revolution. 

PMID- 24579080
TI  - Stereotactic radiosurgery with neoadjuvant embolization of larger arteriovenous
      malformations: an institutional experience.
AB  - OBJECTIVE: This study investigates the safety and efficacy of a multimodality
      approach combining staged endovascular embolizations with subsequent SRS for the
      management of larger AVMs. METHODS: Ninety-five patients with larger AVMs were
      treated with staged endovascular embolization followed by SRS between 1996 and
      2011. RESULTS: The median volume of AVM in this series was 28 cm(3) and 47
      patients (48%) were Spetzler-Martin grade IV or V. Twenty-seven patients
      initially presented with hemorrhage. Sixty-one patients underwent multiple
      embolizations while a single SRS session was performed in 64 patients. The median
      follow-up after SRS session was 32 months (range 9-136 months). Overall
      procedural complications occurred in 14 patients. There were 13 minor neurologic
      complications and 1 major complication (due to embolization) while four patients
      had posttreatment hemorrhage. Thirty-eight patients (40%) were cured
      radiographically. The postradiosurgery actuarial rate of obliteration was 45% at
      5 years, 56% at 7 years, and 63% at 10 years. In multivariate analysis, larger
      AVM size, deep venous drainage, and the increasing number of embolization/SRS
      sessions were negative predictors of obliteration. The number of embolizations
      correlated positively with the number of stereotactic radiosurgeries (P < 0.005).
      CONCLUSIONS: Multimodality endovascular and radiosurgical approach is an
      efficacious treatment strategy for large AVM.

PMID- 24579081
TI  - Induction of apoptosis of 2,4',6-trihydroxybenzophenone in HT-29 colon carcinoma
      cell line.
AB  - 2,4',6-Trihydroxy-4-methoxybenzophenone was isolated from the ethyl acetate
      fraction of Phaleria macrocarpa (Scheff.) Boerl. fruits. It was found to inhibit
      cell proliferation in HT-29 human colon carcinoma cell line but caused little
      damage to WRL-68 normal human liver and MRC-5 normal human fibroblast lung cell
      lines. The compound was found to sharply affect the viability of HT-29 cells in a
      dose- and time-dependent manner. HT-29 cells treated with the compound showed
      morphological changes under microscopic examination such as cell shrinkage,
      membrane blebbing, DNA fragmentation, and the occurrence of apoptotic nuclei. The
      percentage of early apoptotic, late apoptotic, and dead or necrotic cells was
      determined by flow cytometry using annexin V-FTIC/PI staining. In addition, flow
      cytometry showed that, when the HT-29 cells were treated with 115 uM of the
      compound, it resulted in G0/G1 phase arrest in a time-dependent manner. Western
      blot revealed an upregulation of PUMA, Bak, Bcl-2, and Mcl-1 proteins suggesting
      that the compound induced apoptosis in HT-29 cells by regulating these proteins. 

PMID- 24579082
TI  - Comparison of semi-automated and manual measurements of carotid intima-media
      thickening.
AB  - Carotid intima-media thickening (CIMT) is a marker of both arteriosclerotic and
      atherosclerotic risks. Technological advances have semiautomated CIMT image
      acquisition and quantification. Studies comparing manual and automated methods
      have yielded conflicting results possibly due to plaque inclusion in
      measurements. Low atherosclerotic risk subjects (n = 126) were recruited to
      minimise the effect of focal atherosclerotic lesions on CIMT variability. CIMT
      was assessed by high-resolution B-mode ultrasound (Philips HDX7E, Phillips, UK)
      images of the common carotid artery using both manual and semiautomated methods
      (QLAB, Phillips, UK). Intraclass correlation coefficient (ICC) and the mean
      differences of paired measurements (Bland-Altman method) were used to compare
      both methodologies. The ICC of manual (0.547 +/- 0.095 mm) and automated (0.524
      +/- 0.068 mm) methods was R = 0.74 and an absolute mean bias +/- SD of 0.023 +/-
      0.052 mm was observed. Interobserver and intraobserver ICC were greater for
      automated (R = 0.94 and 0.99) compared to manual (R = 0.72 and 0.88) methods.
      Although not considered to be clinically significant, manual measurements yielded
      higher values compared to automated measurements. Automated measurements were
      more reproducible and showed lower interobserver variation compared to manual
      measurements. These results offer important considerations for large
      epidemiological studies. 

PMID- 24579084
TI  - DNA methylation pattern in overweight women under an energy-restricted diet
      supplemented with fish oil.
AB  - Dietary factors modulate gene expression and are able to alter epigenetic
      signatures in peripheral blood mononuclear cells (PBMC). However, there are
      limited studies about the effects of omega-3 polyunsaturated fatty acids (n-3
      PUFA) on the epigenetic mechanisms that regulate gene expression. This research
      investigates the effects of n-3-rich fish oil supplementation on DNA methylation
      profile of several genes whose expression has been reported to be downregulated
      by n-3 PUFA in PBMC: CD36, FFAR3, CD14, PDK4, and FADS1. Young overweight women
      were supplemented with fish oil or control in a randomized 8-week intervention
      trial following a balanced diet with 30% energy restriction. Fatty acid receptor
      CD36 decreased DNA methylation at CpG +477 due to energy restriction. Hypocaloric
      diet-induced weight loss also reduced the methylation percentages of CpG sites
      located in CD14, PDK4, and FADS1. The methylation patterns of these genes were
      only slightly affected by the fish oil supplementation, being the most relevant
      to the attenuation of the weight loss-induced decrease in CD36 methylation after
      adjusting by baseline body weight. These results suggest that the n-3 PUFA
      induced changes in the expression of these genes in PBMC are not mediated by DNA
      methylation, although other epigenetic mechanisms cannot be discarded. 

PMID- 24579083
TI  - Factors determining disease duration in Alzheimer's disease: a postmortem study
      of 103 cases using the Kaplan-Meier estimator and Cox regression.
AB  - Factors associated with duration of dementia in a consecutive series of 103
      Alzheimer's disease (AD) cases were studied using the Kaplan-Meier estimator and
      Cox regression analysis (proportional hazard model). Mean disease duration was
      7.1 years (range: 6 weeks-30 years, standard deviation = 5.18); 25% of cases died
      within four years, 50% within 6.9 years, and 75% within 10 years. Familial AD
      cases (FAD) had a longer duration than sporadic cases (SAD), especially cases
      linked to presenilin (PSEN) genes. No significant differences in duration were
      associated with age, sex, or apolipoprotein E (Apo E) genotype. Duration was
      reduced in cases with arterial hypertension. Cox regression analysis suggested
      longer duration was associated with an earlier disease onset and increased senile
      plaque (SP) and neurofibrillary tangle (NFT) pathology in the orbital gyrus
      (OrG), CA1 sector of the hippocampus, and nucleus basalis of Meynert (NBM). The
      data suggest shorter disease duration in SAD and in cases with hypertensive
      comorbidity. In addition, degree of neuropathology did not influence survival,
      but spread of SP/NFT pathology into the frontal lobe, hippocampus, and basal
      forebrain was associated with longer disease duration. 

PMID- 24579085
TI  - Serum and urinary NGAL in septic newborns.
AB  - Neutrophil gelatinase-associated lipocalin (NGAL) is postulated to be a
      potentially new and highly specific/sensitive marker of acute kidney injury
      (AKI). The aim of this study was to assess the impact of inflammation on serum
      and urine NGAL in newborns that were treated due to infection. We determined
      serum and urine NGAL concentrations in 73 infants (51 with sepsis; 22 with severe
      sepsis) admitted to the Intensive Care Unit in the first month of life, for three
      consecutive days during the course of treatment for infection. 29 neonates
      without infection served as the control group. Septic patients, in particular,
      severe sepsis patients, had increased serum and urinary NGAL levels in the three
      subsequent days of observation. Five septic patients who developed AKI had
      elevated serum and urinary NGAL values to a similar extent as septic neonates
      without AKI. A strong correlation was found between the concentration of serum
      and urinary NGAL and inflammatory markers, such as CRP and procalcitonin. Serum
      and urinary NGAL levels were also significantly associated with NTISS (neonatal
      therapeutic intervention scoring system) values. We conclude that increased serum
      and urinary NGAL values are not solely a marker of AKI, and more accurately
      reflect the severity of inflammatory status. 

PMID- 24579086
TI  - Regular aerobic training combined with range of motion exercises in juvenile
      idiopathic arthritis.
AB  - OBJECTIVE: To assess the effects of regular aerobic training combined with range
      of motion (ROM) exercises on aerobic capacity, quality of life, and function in
      children with juvenile idiopathic arthritis (JIA). METHODS: Thirty patients with
      JIA and 20 healthy age-matched controls (mean age +/- SD, 11.3 +/- 2.4 versus
      11.0 +/- 2.3, resp.; P > 0.05) were included. All patients performed aerobic
      walking (4 days a week for 8 weeks) and active and passive ROM exercises of
      involved joints. All patients completed the childhood health assessment
      questionnaire (CHAQ) and the child health questionnaire. ROM measurements of
      joints were performed by using universal goniometer. Aerobic capacity was
      determined by measuring peak oxygen uptake (VO2peak) during an incremental
      treadmill test. RESULTS: Peak oxygen uptake and exercise duration were
      significantly lower in JIA group than in controls (32.5 +/- 6.6 versus 35.9 +/-
      5.8 and 13.9 +/- 1.9 versus 15.0 +/- 2.0, resp.; P < 0.05 for both). Eight-week
      combined exercise program significantly improved exercise parameters of JIA
      patients (baseline versus postexercise VO2peak and exercise duration, 32.5 +/-
      6.6 to 35.3 +/- 7.9 and 13.9 +/- 1.9 to 16.3 +/- 2.2, resp.; P < 0.001 for both).
      Exercise intervention significantly improved CHAQ scores in JIA patients (0.77 +/
      0.61 to 0.20 +/- 0.28, P < 0.001). CONCLUSION: We suggest that regular aerobic
      exercise combined with ROM exercises may be an important part of treatment in
      patients with JIA.

PMID- 24579087
TI  - A novel approach for discovering condition-specific correlations of gene
      expressions within biological pathways by using cloud computing technology.
AB  - Microarrays are widely used to assess gene expressions. Most microarray studies
      focus primarily on identifying differential gene expressions between conditions
      (e.g., cancer versus normal cells), for discovering the major factors that cause
      diseases. Because previous studies have not identified the correlations of
      differential gene expression between conditions, crucial but abnormal regulations
      that cause diseases might have been disregarded. This paper proposes an approach
      for discovering the condition-specific correlations of gene expressions within
      biological pathways. Because analyzing gene expression correlations is time
      consuming, an Apache Hadoop cloud computing platform was implemented. Three
      microarray data sets of breast cancer were collected from the Gene Expression
      Omnibus, and pathway information from the Kyoto Encyclopedia of Genes and Genomes
      was applied for discovering meaningful biological correlations. The results
      showed that adopting the Hadoop platform considerably decreased the computation
      time. Several correlations of differential gene expressions were discovered
      between the relapse and nonrelapse breast cancer samples, and most of them were
      involved in cancer regulation and cancer-related pathways. The results showed
      that breast cancer recurrence might be highly associated with the abnormal
      regulations of these gene pairs, rather than with their individual expression
      levels. The proposed method was computationally efficient and reliable, and
      stable results were obtained when different data sets were used. The proposed
      method is effective in identifying meaningful biological regulation patterns
      between conditions. 

PMID- 24579089
TI  - Novel method of screening the oxidation and reduction abilities of photocatalytic
      materials.
AB  - Two analytical methods for the evaluation of photocatalytic oxidation and
      reduction abilities were developed using a photocatalytic microreactor; one is
      product analysis and the other is reaction rate analysis. Two simple organic
      conversion reactions were selected for the oxidation and reduction. Since the
      reactions were one-to-one conversions from the reactant species to the product
      species, the product analysis was simply performed using gas chromatography, and
      the reactions were monitored in situ in the photocatalytic microreactor using the
      UV absorption spectra. The partial oxidation and reduction abilities for each
      functional group can be judged from the yield and selectivity, and the
      corresponding reaction rate, while the total oxidation ability can be judged from
      the conversion. We demonstrated the application of these methods for several
      kinds of visible light photocatalysts. 

PMID- 24579090
TI  - Direct N9-arylation of purines with aryl halides.
AB  - An efficient method for N-arylation of purines is reported. The N-arylation is
      catalysed by Cu(i) and 4,7-bis(2-hydroxyethylamino)-1,10-phenanthroline (BHPhen)
      in aqueous DMF or ethanol. The reaction generally proceeds with high selectivity
      for the N(9)-position. 

PMID- 24579088
TI  - Mesothelin-specific chimeric antigen receptor mRNA-engineered T cells induce anti
      tumor activity in solid malignancies.
AB  - Off-target toxicity due to the expression of target antigens in normal tissue
      represents a major obstacle to the use of chimeric antigen receptor (CAR)
      engineered T cells for treatment of solid malignancies. To circumvent this issue,
      we established a clinical platform for engineering T cells with transient CAR
      expression by using in vitro transcribed mRNA encoding a CAR that includes both
      the CD3-zeta and 4-1BB co-stimulatory domains. We present two case reports from
      ongoing trials indicating that adoptive transfer of mRNA CAR T cells that target
      mesothelin (CARTmeso cells) is feasible and safe without overt evidence of off
      tumor on-target toxicity against normal tissues. CARTmeso cells persisted
      transiently within the peripheral blood after intravenous administration and
      migrated to primary and metastatic tumor sites. Clinical and laboratory evidence
      of antitumor activity was demonstrated in both patients and the CARTmeso cells
      elicited an antitumor immune response revealed by the development of novel anti
      self antibodies. These data demonstrate the potential of utilizing mRNA
      engineered T cells to evaluate, in a controlled manner, potential off-tumor on
      target toxicities and show that short-lived CAR T cells can induce epitope
      spreading and mediate antitumor activity in patients with advanced cancer. Thus,
      these findings support the development of mRNA CAR-based strategies for carcinoma
      and other solid tumors. 

PMID- 24579091
TI  - Initial experience of intraoperative three-dimensional navigation for liver
      resection using real-time virtual sonography.
AB  - BACKGROUND: Real-time virtual sonography is an innovative imaging technology that
      detects the spatial position of an ultrasound probe and immediately reconstructs
      a section of computed tomography (CT) and/or magnetic resonance in accordance
      with the ultrasound image, thereby allowing a real-time comparison of those
      modalities. A novel intraoperative navigation system for liver resection using
      real-time virtual sonography has been devised for the detection of tumors and
      navigation of the resection plane. METHODS: Sixteen patients with hepatic
      malignancies (26 tumors in total) were involved in this study, and the system was
      used intraoperatively. The tumor size ranged 2 to 140 mm (23 mm in median). By
      the navigation system, operators could refer intraoperative ultrasound image
      displayed on the television monitor side-by-side with corresponding images of CT
      and/or magnetic resonance. In addition, the system overlaid preoperative
      simulation on the CT image and highlighted the extent of resection so as to
      navigate the resection plane. Because the system used electromagnetic power in
      the operation room, the feasibility and safety of the system was investigated as
      well as its validity. RESULTS: The system could be used uneventfully in each
      operation. All of the 26 tumors scheduled to be resected were detected by the
      navigation system. The weight of the resected specimen correlated with the
      preoperatively simulated volume (R = 0.995, P < .0001). CONCLUSION: The
      feasibility and safety of the navigation system were confirmed. The system should
      be helpful for intraoperative tumor detection and navigation of liver resection.

PMID- 24579092
TI  - Respecting autonomy in the setting of acute traumatic quadriplegia.

PMID- 24579093
TI  - [Reply].

PMID- 24579094
TI  - The value of colonoscopy.

PMID- 24579095
TI  - Computer science: Hacking into the cyberworld.

PMID- 24579096
TI  - Mid-term results of the FPV patellofemoral joint replacement.
AB  - BACKGROUND: Isolated patellofemoral joint osteoarthritis affects approximately
      10% of patients aged over 40 years and treatment remains controversial. The
      Femoro Patella Vialli (FPV) patellofemoral joint replacement (Wright Medical
      Technology, UK) has been shown to restore functional kinematics of the knee close
      to normal. Despite its increasing popularity in recent years, there are no
      studies evaluating the mid-term results with an objective scoring assessment.
      AIMS: Therefore, the aim of this study was to report the clinical and
      radiological outcomes of FPV patellofemoral joint replacement in patients with
      isolated patellofemoral arthritis. METHODS: Between 2006 and 2012,we performed 53
      consecutive FPV patellofemoral arthroplasties in 41 patients with isolated
      patellofemoral joint osteoarthritis. The mean follow-up was 3 years. RESULTS:
      Mean Oxford Knee Scores improved from 19.7 to 37.7 at latest follow-up. The
      progression of tibiofemoral osteoarthritis was seen 12% of knees. Two knees
      required revision to TKR at 7 months post-operatively, which we attribute to poor
      patient selection. We had no cases of maltracking patellae, and no lateral
      releases were performed. CONCLUSION: Our findings suggest the FPV patellofemoral
      prosthesis provides good pain relief and survivorship with no significant
      maltracking patellae.

PMID- 24579097
TI  - Fish have feelings too.

PMID- 24579098
TI  - Parallel lines.

PMID- 24579100
TI  - Earth science: Crystallography's journey to the deep Earth.

PMID- 24579099
TI  - Virgin territory.

PMID- 24579101
TI  - [Week of Sight (WDS) and Vision 2020].

PMID- 24579102
TI  - [Since October, there is only one federal master contract].

PMID- 24579103
TI  - [Presenteeism: work despite illness].

PMID- 24579104
TI  - [The TNM and WHO classifications of neuroendoctine neoplasia of the pancreas].

PMID- 24579105
TI  - [Transcutaneous transhepatic interventions for the treatment of biliary
      hypertension].

PMID- 24579106
TI  - [The clinical presentation, diagnostics and treatment of pathological changes of
      the epiploic appendices].

PMID- 24579107
TI  - [The choice of treatment tactics by the tumor colon obturation].

PMID- 24579108
TI  - Retaining compassion in tough times.

PMID- 24579109
TI  - Developing models of care for the future.

PMID- 24579110
TI  - Nurse registrations up.

PMID- 24579111
TI  - Hundreds of graduates fail to get jobs.

PMID- 24579112
TI  - Serious adverse events increasing.

PMID- 24579113
TI  - Challenging changes to employment law.

PMID- 24579114
TI  - Private hospitals: galvanising the workforce.

PMID- 24579115
TI  - Aged care: caregivers focus on dementia.

PMID- 24579116
TI  - Preface. The 16th International Conference on Medical Image Computing and
      Computer Assisted Intervention, MICCAI 2013 was held in Nagoya, Japan during
      September 22-26, 2013.

PMID- 24579117
TI  - Biomechanically driven registration of pre- to intra-operative 3D images for
      laparoscopic surgery.
AB  - Minimally invasive laparoscopic surgery is widely used for the treatment of
      cancer and other diseases. During the procedure, gas insufflation is used to
      create space for laparoscopic tools and operation. Insufflation causes the organs
      and abdominal wall to deform significantly. Due to this large deformation, the
      benefit of surgical plans, which are typically based on pre-operative images, is
      limited for real time navigation. In some recent work, intra-operative images,
      such as cone-beam CT or interventional CT, are introduced to provide updated
      volumetric information after insufflation. Other works in this area have focused
      on simulation of gas insufflation and exploited only the pre-operative images to
      estimate deformation. This paper proposes a novel registration method for pre-
      and intra-operative 3D image fusion for laparoscopic surgery. In this approach,
      the deformation of pre-operative images is driven by a biomechanical model of the
      insufflation process. The proposed method was validated by five synthetic data
      sets generated from clinical images and three pairs of in vivo CT scans acquired
      from two pigs, before and after insufflation. The results show the proposed
      method achieved high accuracy for both the synthetic and real insufflation data.

PMID- 24579118
TI  - A Bayesian approach for spatially adaptive regularisation in non-rigid
      registration.
AB  - This paper introduces a novel method for inferring spatially varying
      regularisation in non-rigid registration. This is achieved through full Bayesian
      inference on a probabilistic registration model, where the prior on
      transformations is parametrised as a weighted mixture of spatially localised
      components. Such an approach has the advantage of allowing the registration to be
      more flexibly driven by the data than a more traditional global regularisation
      scheme, such as bending energy. The proposed method adaptively determines the
      influence of the prior in a local region. The importance of the prior may be
      reduced in areas where the data better supports deformations, or can enforce a
      stronger constraint in less informative areas. Consequently, the use of such a
      spatially adaptive prior may reduce the unwanted impact of regularisation on the
      inferred deformation field. This is especially important for applications such as
      tensor based morphometry, where the features of interest are directly derived
      from the deformation field. The proposed approach is demonstrated with
      application to tensor based morphometry analysis of subjects with Alzheimer's
      disease and healthy controls. The results show that using the proposed spatially
      adaptive prior leads to deformation fields that have a substantially lower
      average complexity, but which also provide more accurate localisation of
      statistical group differences.

PMID- 24579119
TI  - Geodesic distances to landmarks for dense correspondence on ensembles of complex
      shapes.
AB  - Establishing correspondence points across a set of biomedical shapes is an
      important technology for a variety of applications that rely on statistical
      analysis of individual subjects and populations. The inherent complexity (e.g.
      cortical surface shapes) and variability (e.g. cardiac chambers) evident in many
      biomedical shapes introduce significant challenges in finding a useful set of
      dense correspondences. Application specific strategies, such as registration of
      simplified (e.g. inflated or smoothed) surfaces or relying on manually placed
      landmarks, provide some improvement but suffer from limitations including
      increased computational complexity and ambiguity in landmark placement. This
      paper proposes a method for dense point correspondence on shape ensembles using
      geodesic distances to a priori landmarks as features. A novel set of numerical
      techniques for fast computation of geodesic distances to point sets is used to
      extract these features. The proposed method minimizes the ensemble entropy based
      on these features, resulting in isometry invariant correspondences in a very
      general, flexible framework.

PMID- 24579120
TI  - Large deformation diffeomorphic registration of diffusion-weighted images with
      explicit orientation optimization.
AB  - We seek to compute a diffeomorphic map between a pair of diffusion-weighted
      images under large deformation. Unlike existing techniques, our method allows any
      diffusion model to be fitted after registration for subsequent multifaceted
      analysis. This is achieved by directly aligning the diffusion-weighted images
      using a large deformation diffeomorphic registration framework formulated from an
      optimal control perspective. Our algorithm seeks the optimal coordinate mapping
      by simultaneously considering structural alignment, local fiber reorientation,
      and deformation regularization. Our algorithm also incorporates a multi-kernel
      strategy to concurrently register anatomical structures of different scales. We
      demonstrate the efficacy of our approach using in vivo data and report on
      detailed qualitative and quantitative results in comparison with several
      different registration strategies.

PMID- 24579121
TI  - Atlas construction for dynamic (4D) PET using diffeomorphic transformations.
AB  - A novel dynamic (4D) PET to PET image registration procedure is proposed and
      applied to multiple PET scans acquired with the high resolution research
      tomograph (HRRT), the highest resolution human brain PET scanner available in the
      world. By extending the recent diffeomorphic log-demons (DLD) method and applying
      it to multiple dynamic [11C]raclopride scans from the HRRT, an important step
      towards construction of a PET atlas of unprecedented quality for [11C]raclopride
      imaging of the human brain has been achieved. Accounting for the temporal
      dimension in PET data improves registration accuracy when compared to
      registration of 3D to 3D time-averaged PET images. The DLD approach was chosen
      for its ease in providing both an intensity and shape template, through iterative
      sequential pair-wise registrations with fast convergence. The proposed method is
      applicable to any PET radiotracer, providing 4D atlases with useful applications
      in high accuracy PET data simulations and automated PET image analysis.

PMID- 24579122
TI  - Random walks with efficient search and contextually adapted image similarity for
      deformable registration.
AB  - We develop a random walk-based image registration method that incorporates two
      novelties: 1) a progressive optimization scheme that conducts the solution search
      efficiently via a novel use of information derived from the obtained
      probabilistic solution, and 2) a data-likelihood re-weighting step that
      contextually performs feature selection in a spatially adaptive manner so that
      the data costs are based primarily on trusted information sources. Synthetic
      experiments on three public datasets of different anatomical regions and
      modalities showed that our method performed efficient search without sacrificing
      registration accuracy. Experiments performed on 60 real brain image pairs from a
      public dataset also demonstrated our method's better performance over existing
      non-probabilistic image registration methods.

PMID- 24579123
TI  - A histology-based model of quantitative T1 contrast for in-vivo cortical
      parcellation of high-resolution 7 Tesla brain MR images.
AB  - A conclusive mapping of myeloarchitecture (myelin patterns) onto the cortical
      sheet and, thus, a corresponding mapping to cytoarchitecture (cell configuration)
      does not exist today. In this paper we present a generative model which can
      predict, on the basis of known cytoarchitecture, myeloarchitecture in different
      primary and non-primary cortical areas, resulting in simulated in-vivo
      quantitative T1 maps. The predicted patterns can be used in brain parcellation.
      Our model is validated using a similarity distance metric which enables
      quantitative comparison of the results with empirical data measured using MRI.
      The work presented may provide new perspectives for this line of research, both
      in imaging and in modelling the relationship with myelo- and cytoarchitecture,
      thus leading the way towards in-vivo histology using MRI.

PMID- 24579124
TI  - Apoptosis detection for non-adherent cells in time-lapse phase contrast
      microscopy.
AB  - This paper proposes a vision-based method for detecting apoptosis (programmed
      cell death), which is essential for non-perturbative monitoring of cell
      expansion. Our method targets non-adherent cells, which float or are suspended
      freely in the culture medium-in contrast to adherent cells, which are attached to
      a petri dish. The method first detects cell regions and tracks them over time,
      resulting in the construction of cell tracklets. For each of the tracklets,
      visual properties of the cell are then examined to know whether and when the
      tracklet shows a transition from a live cell to a dead cell, in order to
      determine the occurrence and timing of a cell death event. For the validation, a
      transductive learning framework is adopted to utilize unlabeled data in addition
      to labeled data. Our method achieved promising performance in the experiments
      with hematopoietic stem cell (HSC) populations, which are currently in clinical
      use for rescuing hematopoietic function during bone marrow transplants.

PMID- 24579125
TI  - Pathological site retargeting under tissue deformation using geometrical
      association and tracking.
AB  - Recent advances in microscopic detection techniques include fluorescence
      spectroscopy, fibred confocal microscopy and optical coherence tomography. These
      methods can be integrated with miniaturised probes to assist endoscopy, thus
      enabling diseases to be detected at an early and pre-invasive stage, forgoing the
      need for histopathological samples and off-line analysis. Since optical-based
      biopsy does not leave visible marks after sampling, it is important to track the
      biopsy sites to enable accurate retargeting and subsequent serial examination. In
      this paper, a novel approach is proposed for pathological site retargeting in
      gastroscopic examinations. The proposed method is based on affine deformation
      modelling with geometrical association combined with cascaded online learning and
      tracking. It provides online in vivo retargeting, and is able to track
      pathological sites in the presence of tissue deformation. It is also robust to
      partial occlusions and can be applied to a range of imaging probes including
      confocal laser endomicroscopy.

PMID- 24579126
TI  - Optic disc and cup segmentation from color fundus photograph using graph cut with
      priors.
AB  - For automatic segmentation of optic disc and cup from color fundus photograph, we
      describe a fairly general energy function that can naturally fit into a global
      optimization framework with graph cut. Distinguished from most previous work, our
      energy function includes priors on the shape & location of disc & cup, the rim
      thickness and the geometric interaction of "disc contains cup". These priors
      together with the effective optimization of graph cut enable our algorithm to
      generate reliable and robust solutions. Our approach is able to outperform
      several state-of-the-art segmentation methods, as shown by a set of experimental
      comparisons with manual delineations and a series of results of correlations with
      the assessments of a merchant-provided software from Optical Coherence Tomography
      (OCT) regarding several cup and disc parameters.

PMID- 24579127
TI  - A variational framework for joint detection and segmentation of ovarian cancer
      metastases.
AB  - Detection and segmentation of ovarian cancer metastases have great clinical
      impacts on women's health. However, the random distribution and weak boundaries
      of metastases significantly complicate this task. This paper presents a
      variational framework that combines region competition based level set
      propagation and image matching flow computation to jointly detect and segment
      metastases. Image matching flow not only detects metastases, but also creates
      shape priors to reduce over-segmentation. Accordingly, accurate segmentation
      helps to improve the detection accuracy by separating flow computation in
      metastasis and non-metastasis regions. Since all components in the image
      processing pipeline benefit from each other, our joint framework can achieve
      accurate metastasis detection and segmentation. Validation on 50 patient datasets
      demonstrated that our joint approach was superior to a sequential method with
      sensitivity 89.2% vs. 81.4% (Fisher exact test p = 0.046) and false positive per
      patient 1.04 vs. 2.04. The Dice coefficient of metastasis segmentation was 92 +/-
      5.2% vs. 72 +/- 8% (paired t-test p = 0.022), and the average surface distance
      was 1.9 +/- 1.5mm vs. 4.5 +/- 2.2mm (paired t-test p = 0.004).

PMID- 24579128
TI  - Characterization of tissue histopathology via predictive sparse decomposition and
      spatial pyramid matching.
AB  - Image-based classification of tissue histology, in terms of different components
      (e.g., subtypes of aberrant phenotypic signatures), provides a set of indices for
      tumor composition. Subsequently, integration of these indices in whole slide
      images (WSI), from a large cohort, can provide predictive models of the clinical
      outcome. However, the performance of the existing histology-based classification
      techniques is hindered as a result of large technical and biological variations
      that are always present in a large cohort. In this paper, we propose an algorithm
      for classification of tissue histology based on predictive sparse decomposition
      (PSD) and spatial pyramid matching (SPM), which utilize sparse tissue
      morphometric signatures at various locations and scales. The method has been
      evaluated on two distinct datasets of different tumor types collected from The
      Cancer Genome Atlas (TCGA). The novelties of our approach are: (i) extensibility
      to different tumor types; (ii) robustness in the presence of wide technical and
      biological variations; and (iii) scalability with varying training sample size.

PMID- 24579129
TI  - Registration of free-breathing 3D+t abdominal perfusion CT images via co
      segmentation.
AB  - Dynamic contrast-enhanced computed tomography (DCE-CT) is a valuable imaging
      modality to assess tissues properties, particularly in tumours, by estimating
      pharmacokinetic parameters from the evolution of pixels intensities in 3D+t
      acquisitions. However, this requires a registration of the whole sequence of
      volumes, which is challenging especially when the patient breathes freely. In
      this paper, we propose a generic, fast and automatic method to address this
      problem. As standard iconic registration methods are not robust to contrast
      intake, we rather rely on the segmentation of the organ of interest. This
      segmentation is performed jointly with the registration of the sequence within a
      novel co-segmentation framework. Our approach is based on implicit template
      deformation, that we extend to a co-segmentation algorithm which provides as
      outputs both a segmentation of the organ of interest in every image and
      stabilising transformations for the whole sequence. The proposed method is
      validated on 15 datasets acquired from patients with renal lesions and shows
      improvement in terms of registration and estimation of pharmacokinetic parameters
      over the state-of-the-art method.

PMID- 24579130
TI  - Respiratory motion compensation with relevance vector machines.
AB  - In modern robotic radiation therapy, tumor movements due to respiration can be
      compensated. The accuracy of these methods can be increased by time series
      prediction of external optical surrogates. An algorithm based on relevance vector
      machines (RVM) is introduced. We evaluate RVM with linear and nonlinear basis
      functions on a real patient data set containing 304 motion traces and compare it
      with a wavelet based least mean square algorithm (wLMS), the best algorithm for
      this data set so far. Linear RVM outperforms wLMS significantly and increases the
      prediction accuracy for 80.3% of the data. We show that real time prediction is
      possible in case of linear RVM and discuss how the predicted variance can be used
      to construct promising hybrid algorithms, which further reduce the prediction
      error.

PMID- 24579131
TI  - Real-time respiratory motion analysis using manifold ray casting of
      volumetrically fused multi-view range imaging.
AB  - A novel real-time multi-sensor framework for range imaging (RI) based respiratory
      motion analysis in image guided interventions such as fractionated radiation
      therapy is presented. We constitute our method based upon real-time constraints
      in clinical practice and an analytic analysis of RI based elastic body surface
      deformation fields. For the latter, we show that the underlying joint rigid and
      non-rigid registration problem is ill-conditioned and identify insufficient body
      coverage as an error source. Facing these issues, we propose a novel manifold ray
      casting technique enabling the reconstruction of an 180 degrees coverage body
      surface model composed of - 3 x 10(5) points from volumetrically fused multi-view
      range data in - 25 ms. Exploiting the wide field of view surface model enabled by
      our method, we reduce the error in motion compensated patient alignment by a
      factor of 2.7 in the translational and 2.4 in the rotational component compared
      to conventional single sensor surface coverage.

PMID- 24579132
TI  - Improving 2D-3D registration optimization using learned prostate motion data.
AB  - Prostate motion due to transrectal ultrasound (TRUS) probe pressure and patient
      movement causes target misalignments during 3D TRUS-guided biopsy. Several
      solutions have been proposed to perform 2D-3D registration for motion
      compensation. To improve registration accuracy and robustness, we developed and
      evaluated a registration algorithm whose optimization is based on learned
      prostate motion characteristics relative to different tracked probe positions and
      prostate sizes. We performed a principal component analysis of previously
      observed motions and utilized the principal directions to initialize Powell's
      direction set method during optimization. Compared with the standard
      initialization, our approach improved target registration error to 2.53 +/- 1.25
      mm after registration. Multiple initializations along the major principal
      directions improved the robustness of the method at the cost of additional
      execution time of 1.5 s. With a total execution time of 3.2 s to perform motion
      compensation, this method is amenable to useful integration into a clinical 3D
      guided prostate biopsy workflow.

PMID- 24579133
TI  - Respiratory motion correction in dynamic-MRI: application to small bowel motility
      quantification during free breathin.
AB  - This study introduces a combination of two registration techniques for
      respiratory motion removal and the quantification of small bowel motility from
      free breathing cine MRI. The use of robust data decomposition registration (RDDR)
      allows for exclusive correction of respiratory motion in order to avoid errors in
      further analysis of motility due to the effects of breathing. The proposed method
      is assessed using regions of interest (ROIs) contoured in dynamic MRI of six
      healthy volunteers. The use of RDDR prior to motility quantification results in
      reduced errors on motility scores in ROIs, with respect to breath-holds.

PMID- 24579134
TI  - Non-rigid deformation pipeline for compensation of superficial brain shift.
AB  - The correct visualization of anatomical structures is a critical component of
      neurosurgical navigation systems, to guide the surgeon to the areas of interest
      as well as to avoid brain damage. A major challenge for neuronavigation systems
      is the brain shift, or deformation of the exposed brain in comparison to
      preoperative Magnetic Resonance (MR) image sets. In this work paper, a non-rigid
      deformation pipeline is proposed for brain shift compensation of preoperative
      imaging datasets using superficial blood vessels as landmarks. The input was
      preoperative and intraoperative 3D image sets of superficial vessel centerlines.
      The intraoperative vessels (obtained using 3 Near-Infrared cameras) were
      registered and aligned with preoperative Magnetic Resonance Angiography vessel
      centerlines using manual interaction for the rigid transformation and, for the
      non-rigid transformation, the non-rigid point set registration method Coherent
      Point Drift. The rigid registration transforms the intraoperative points from the
      camera coordinate system to the preoperative MR coordinate system, and the non
      rigid registration deals with local transformations in the MR coordinate system.
      Finally, the generation of a new deformed volume is achieved with the Thin-Plate
      Spline (TPS) method using as control points the matches in the MR coordinate
      system found in the previous step. The method was tested in a rabbit brain
      exposed via craniotomy, where deformations were produced by a balloon inserted
      into the brain. There was a good correlation between the real state of the brain
      and the deformed volume obtained using the pipeline. Maximum displacements were
      approximately 4.0 mm for the exposed brain alone, and 6.7 mm after balloon
      inflation.

PMID- 24579135
TI  - A symmetric 4D registration algorithm for respiratory motion modeling.
AB  - We propose an effective 4D image registration algorithm for dynamic volumetric
      lung images. The registration will construct a deforming 3D model with continuous
      trajectory and smooth spatial deformation, and the model interpolates the
      interested region in the 4D (3D+T) CT images. The resultant non-rigid
      transformation is represented using two 4D B-spline functions, indicating a
      forward and an inverse 4D parameterization respectively. The registration process
      solves these two functions by minimizing an objective function that penalizes
      intensity matching error, feature alignment error, spatial and temporal non
      smoothness, and inverse inconsistency. We test our algorithm for respiratory
      motion estimation on public benchmarks and on clinic lung CT data. The
      experimental results demonstrate the efficacy of our algorithm.

PMID- 24579136
TI  - Collaborative multi organ segmentation by integrating deformable and graphical
      models.
AB  - Organ segmentation is a challenging problem on which significant progress has
      been made. Deformable models (DM) and graphical models (GM) are two important
      categories of optimization based image segmentation methods. Efforts have been
      made on integrating two types of models into one framework. However, previous
      methods are not designed for segmenting multiple organs simultaneously and
      accurately. In this paper, we propose a hybrid multi organ segmentation approach
      by integrating DM and GM in a coupled optimization framework. Specifically, we
      show that region-based deformable models can be integrated with Markov Random
      Fields (MRF), such that multiple models' evolutions are driven by a maximum a
      posteriori (MAP) inference. It brings global and local deformation constraints
      into a unified framework for simultaneous segmentation of multiple objects in an
      image. We validate this proposed method on two challenging problems of multi
      organ segmentation, and the results are promising.

PMID- 24579137
TI  - Multi-organ segmentation based on spatially-divided probabilistic atlas from 3D
      abdominal CT images.
AB  - This paper presents an automated multi-organ segmentation method for 3D abdominal
      CT images based on a spatially-divided probabilistic atlases. Most previous
      abdominal organ segmentation methods are ineffective to deal with the large
      differences among patients in organ shape and position in local areas. In this
      paper, we propose an automated multi-organ segmentation method based on a
      spatially-divided probabilistic atlas, and solve this problem by introducing a
      scale hierarchical probabilistic atlas. The algorithm consists of image-space
      division and a multi-scale weighting scheme. The generated spatial-divided
      probabilistic atlas efficiently reduces the inter-subject variance in organ shape
      and position either in global or local regions. Our proposed method was evaluated
      using 100 abdominal CT volumes with manually traced ground truth data.
      Experimental results showed that it can segment the liver, spleen, pancreas, and
      kidneys with Dice similarity indices of 95.1%, 91.4%, 69.1%, and 90.1%,
      respectively.

PMID- 24579138
TI  - An automatic multi-atlas segmentation of the prostate in transrectal ultrasound
      images using pairwise atlas shape similarity.
AB  - Delineation of the prostate from transrectal ultrasound images is a necessary
      step in several computer-assisted clinical interventions, such as low dose rate
      brachytherapy. Current approaches to user segmentation require user intervention
      and therefore it is subject to user errors. It is desirable to have a fully
      automatic segmentation for improved segmentation consistency and speed. In this
      paper, we propose a multi-atlas fusion framework to automatically segment
      prostate transrectal ultrasound images. The framework initially registers a
      dataset of a priori segmented ultrasound images to a target image. Subsequently,
      it uses the pairwise similarity of registered prostate shapes, which is
      independent of the image-similarity metric optimized during the registration
      process, to prune the dataset prior to the fusion and consensus segmentation
      step. A leave-one-out cross-validation of the proposed framework on a dataset of
      50 transrectal ultrasound volumes obtained from patients undergoing brachytherapy
      treatment shows that the proposed is clinically robust, accurate and
      reproducible.

PMID- 24579139
TI  - Accurate bone segmentation in 2D radiographs using fully automatic shape model
      matching based on regression-voting.
AB  - Recent work has shown that using Random Forests (RFs) to vote for the optimal
      position of model feature points leads to robust and accurate shape model
      matching. This paper applies RF regression-voting as part of a fully automatic
      shape model matching (FASMM) system to three different radiograph segmentation
      problems: the proximal femur, the bones of the knee joint and the joints of the
      hand. We investigate why this approach works so well and demonstrate that the
      performance comes from a combination of three properties: (i) The integration of
      votes from multiple regions around the model point. (ii) The combination of
      multiple independent votes from each tree. (iii) The use of a coarse to fine
      strategy. We show that each property can improve performance, and that the best
      performance comes from using all three. We demonstrate that FASMM based on RF
      regression-voting generalises well across application areas, achieving state of
      the art performance in each of the three segmentation problems. This FASMM system
      provides an accurate and time-efficient way for the segmentation of bony
      structures in radiographs.

PMID- 24579140
TI  - Automated CT segmentation of diseased hip using hierarchical and conditional
      statistical shape models.
AB  - Segmentation of the femur and pelvis is a prerequisite for patient-specific
      planning and simulation for hip surgery. Accurate boundary determination of the
      femoral head and acetabulum is the primary challenge in diseased hip joints
      because of deformed shapes and extreme narrowness of the joint space. To overcome
      this difficulty, we investigated a multi-stage method in which the hierarchical
      hip statistical shape model (SSM) is initially utilized to complete segmentation
      of the pelvis and distal femur, and then the conditional femoral head SSM is used
      under the condition that the regions segmented during the previous stage are
      known. CT data from 100 diseased patients categorized on the basis of their
      disease type and severity, which included 200 hemi-hips, were used to validate
      the method, which delivered significantly increased segmentation accuracy for the
      femoral head.

PMID- 24579141
TI  - Fast globally optimal segmentation of 3D prostate MRI with axial symmetry prior.
AB  - We propose a novel global optimization approach to segmenting a given 3D prostate
      T2w magnetic resonance (MR) image, which enforces the inherent axial symmetry of
      the prostate shape and simultaneously performs a sequence of 2D axial slice-wise
      segmentations with a global 3D coherence prior. We show that the proposed
      challenging combinatorial optimization problem can be solved globally and exactly
      by means of convex relaxation. With this regard, we introduce a novel coupled
      continuous max-flow model, which is dual to the studied convex relaxed
      optimization formulation and leads to an efficient multiplier augmented algorithm
      based on the modern convex optimization theory. Moreover, the new continuous max
      flow based algorithm was implemented on GPUs to achieve a substantial improvement
      in computation. Experimental results using public and in-house datasets
      demonstrate great advantages of the proposed method in terms of both accuracy and
      efficiency.

PMID- 24579142
TI  - Image segmentation errors correction by mesh segmentation and deformation.
AB  - Volumetric image segmentation methods often produce delineations of anatomical
      structures and pathologies that require user modifications. We present a new
      method for the correction of segmentation errors. Given an initial geometrical
      mesh, our method semi automatically identifies the mesh vertices in erroneous
      regions with min-cut segmentation. It then deforms the mesh by correcting its
      vertex coordinates with Laplace deformation based on local geometrical
      properties. The key advantages of our method are that: (1) it supports fast user
      interaction on a single surface rendered 2D view; (2) its parameters values are
      fixed to the same value for all cases; (3) it is independent of the initial
      segmentation method, and; (4) it is applicable to a variety of anatomical
      structures and pathologies. Experimental evaluation on 44 initial segmentations
      of kidney and kidney vessels from CT scans show an improvement of 83% and 75% in
      the average surface distance and the volume overlap error between the initial and
      the corrected segmentations with respect to the ground-truth.

PMID- 24579143
TI  - Semi-supervised and active learning for automatic segmentation of Crohn's
      disease.
AB  - Our proposed method combines semi supervised learning (SSL) and active learning
      (AL) for automatic detection and segmentation of Crohn's disease (CD) from
      abdominal magnetic resonance (MR) images. Random forest (RF) classifiers are used
      due to fast SSL classification and capacity to interpret learned knowledge. Query
      samples for AL are selected by a novel information density weighted approach
      using context information, semantic knowledge and labeling uncertainty.
      Experimental results show that our proposed method combines the advantages of SSL
      and AL, and with fewer samples achieves higher classification and segmentation
      accuracy over fully supervised methods.

PMID- 24579144
TI  - Hierarchical constrained local model using ICA and its application to Down
      syndrome detection.
AB  - Conventional statistical shape models use Principal Component Analysis (PCA) to
      describe shape variations. However, such a PCA-based model assumes a Gaussian
      distribution of data. A model with Independent Component Analysis (ICA) does not
      require the Gaussian assumption and can additionally describe the local shape
      variation. In this paper, we propose a Hierarchical Constrained Local Model
      (HCLM) using ICA. The first or coarse level of HCLM locates the full landmark
      set, while the second level refines a relevant landmark subset. We then apply the
      HCLM to Down syndrome detection from photographs of young pediatric patients.
      Down syndrome is the most common chromosomal condition and its early detection is
      crucial. After locating facial anatomical landmarks using HCLM, geometric and
      local texture features are extracted and selected. A variety of classifiers are
      evaluated to identify Down syndrome from a healthy population. The best
      performance achieved 95.6% accuracy using support vector machine with radial
      basis function kernel. The results show that the ICA-based HCLM outperformed both
      PCA-based CLM and ICA-based CLM.

PMID- 24579145
TI  - Learning from multiple experts with random forests: application to the
      segmentation of the midbrain in 3D ultrasound.
AB  - In the field of computer aided medical image analysis, it is often difficult to
      obtain reliable ground truth for evaluating algorithms or supervising statistical
      learning procedures. In this paper we present a new method for training a
      classification forest from images labelled by variably performing experts, while
      simultaneously evaluating the performance of each expert. Our approach builds
      upon state-of-the-art randomized classification forest techniques for medical
      image segmentation and recent methods for the fusion of multiple expert
      decisions. By incorporating the performance evaluation within the training phase,
      we obtain a novel forest framework for learning from conflicting expert
      decisions, accounting for both inter- and intra-expert variability. We
      demonstrate on a synthetic example that our method allows to retrieve the correct
      segmentation among other incorrectly labelled images, and we present an
      application to the automatic segmentation of the midbrain in 3D transcranial
      ultrasound images.

PMID- 24579146
TI  - Variable importance in nonlinear kernels (VINK): classification of digitized
      histopathology.
AB  - Quantitative histomorphometry is the process of modeling appearance of disease
      morphology on digitized histopathology images via image-based features (e.g.,
      texture, graphs). Due to the curse of dimensionality, building classifiers with
      large numbers of features requires feature selection (which may require a large
      training set) or dimensionality reduction (DR). DR methods map the original high
      dimensional features in terms of eigenvectors and eigenvalues, which limits the
      potential for feature transparency or interpretability. Although methods exist
      for variable selection and ranking on embeddings obtained via linear DR schemes
      (e.g., principal components analysis (PCA)), similar methods do not yet exist for
      nonlinear DR (NLDR) methods. In this work we present a simple yet elegant method
      for approximating the mapping between the data in the original feature space and
      the transformed data in the kernel PCA (KPCA) embedding space; this mapping
      provides the basis for quantification of variable importance in nonlinear kernels
      (VINK). We show how VINK can be implemented in conjunction with the popular
      Isomap and Laplacian eigenmap algorithms. VINK is evaluated in the contexts of
      three different problems in digital pathology: (1) predicting five year PSA
      failure following radical prostatectomy, (2) predicting Oncotype DX recurrence
      risk scores for ER+ breast cancers, and (3) distinguishing good and poor outcome
      p16+ oropharyngeal tumors. We demonstrate that subsets of features identified by
      VINK provide similar or better classification or regression performance compared
      to the original high dimensional feature sets.

PMID- 24579147
TI  - Deep feature learning for knee cartilage segmentation using a triplanar
      convolutional neural network.
AB  - Segmentation of anatomical structures in medical images is often based on a
      voxel/pixel classification approach. Deep learning systems, such as convolutional
      neural networks (CNNs), can infer a hierarchical representation of images that
      fosters categorization. We propose a novel system for voxel classification
      integrating three 2D CNNs, which have a one-to-one association with the xy, yz
      and zx planes of 3D image, respectively. We applied our method to the
      segmentation of tibial cartilage in low field knee MRI scans and tested it on 114
      unseen scans. Although our method uses only 2D features at a single scale, it
      performs better than a state-of-the-art method using 3D multi-scale features. In
      the latter approach, the features and the classifier have been carefully adapted
      to the problem at hand. That we were able to get better results by a deep
      learning architecture that autonomously learns the features from the images is
      the main insight of this study.

PMID- 24579149
TI  - Vertebrae localization in pathological spine CT via dense classification from
      sparse annotations.
AB  - Accurate localization and identification of vertebrae in spinal imaging is
      crucial for the clinical tasks of diagnosis, surgical planning, and post
      operative assessment. The main difficulties for automatic methods arise from the
      frequent presence of abnormal spine curvature, small field of view, and image
      artifacts caused by surgical implants. Many previous methods rely on parametric
      models of appearance and shape whose performance can substantially degrade for
      pathological cases. We propose a robust localization and identification algorithm
      which builds upon supervised classification forests and avoids an explicit
      parametric model of appearance. We overcome the tedious requirement for dense
      annotations by a semi-automatic labeling strategy. Sparse centroid annotations
      are transformed into dense probabilistic labels which capture the inherent
      identification uncertainty. Using the dense labels, we learn a discriminative
      centroid classifier based on local and contextual intensity features which is
      robust to typical characteristics of spinal pathologies and image artifacts.
      Extensive evaluation is performed on a challenging dataset of 224 spine CT scans
      of patients with varying pathologies including high-grade scoliosis, kyphosis,
      and presence of surgical implants. Additionally, we test our method on a
      heterogeneous dataset of another 200, mostly abdominal, CTs. Quantitative
      evaluation is carried out with respect to localization errors and identification
      rates, and compared to a recently proposed method. Our approach is efficient and
      outperforms state-of-the-art on pathological cases.

PMID- 24579148
TI  - Representation learning: a unified deep learning framework for automatic prostate
      MR segmentation.
AB  - Image representation plays an important role in medical image analysis. The key
      to the success of different medical image analysis algorithms is heavily
      dependent on how we represent the input data, namely features used to
      characterize the input image. In the literature, feature engineering remains as
      an active research topic, and many novel hand-crafted features are designed such
      as Haar wavelet, histogram of oriented gradient, and local binary patterns.
      However, such features are not designed with the guidance of the underlying
      dataset at hand. To this end, we argue that the most effective features should be
      designed in a learning based manner, namely representation learning, which can be
      adapted to different patient datasets at hand. In this paper, we introduce a deep
      learning framework to achieve this goal. Specifically, a stacked independent
      subspace analysis (ISA) network is adopted to learn the most effective features
      in a hierarchical and unsupervised manner. The learnt features are adapted to the
      dataset at hand and encode high level semantic anatomical information. The
      proposed method is evaluated on the application of automatic prostate MR
      segmentation. Experimental results show that significant segmentation accuracy
      improvement can be achieved by the proposed deep learning method compared to
      other state-of-the-art segmentation approaches.

PMID- 24579150
TI  - A multi-task learning approach for compartmental model parameter estimation in
      DCE-CT sequences.
AB  - Today's follow-up of patients presenting abdominal tumors is generally performed
      through acquisition of dynamic sequences of contrast-enhanced CT. Estimating
      parameters of appropriate models of contrast intake diffusion through tissues
      should help characterizing the tumor physiology, but is impeded by the high level
      of noise inherent to the acquisition conditions. To improve the quality of
      estimation, we consider parameter estimation in voxels as a multi-task learning
      problem (one task per voxel) that takes advantage from the similarity between two
      tasks. We introduce a temporal similarity between tasks based on a robust
      distance between observed contrast-intake profiles of intensity. Using synthetic
      images, we compare multi-task learning using this temporal similarity, a spatial
      similarity and a single-task learning. The similarities based on temporal
      profiles are shown to bring significant improvements compared to the spatial one.
      Results on real CT sequences also confirm the relevance of the approach.

PMID- 24579151
TI  - Ultrasound-based characterization of prostate cancer: an in vivo clinical
      feasibility study.
AB  - This paper presents the results of an in vivo clinical study to accurately
      characterize prostate cancer using new features of ultrasound RF time series.
      METHODS: The mean central frequency and wavelet features of ultrasound RF time
      series from seven patients are used along with an elaborate framework of
      ultrasound to histology registration to identify and verify cancer in prostate
      tissue regions as small as 1.7 mm x 1.7 mm. RESULTS: In a leave-one-patient-out
      cross-validation strategy, an average classification accuracy of 76% and the area
      under ROC curve of 0.83 are achieved using two proposed RF time series features.
      The results statistically significantly outperform those achieved by previously
      reported features in the literature. The proposed features show the clinical
      relevance of RF time series for in vivo characterization of cancer.

PMID- 24579152
TI  - Quantitative airway analysis in longitudinal studies using groupwise registration
      and 4D optimal surfaces.
AB  - Quantifying local changes to the airway wall surfaces from computed tomography
      images is important in the study of diseases such as chronic obstructive
      pulmonary disease. Current approaches segment the airways in the individual time
      point images and subsequently aggregate per airway generation or perform branch
      matching to assess regional changes. In contrast, we propose an integrated
      approach analysing the time points simultaneously using a subject-specific
      groupwise space and 4D optimal surface segmentation. The method combines
      information from all time points and measurements are matched locally at any
      position on the resulting surfaces. Visual inspection of the scans of 10 subjects
      showed increased tree length compared to the state of the art with little change
      in the amount of false positives. A large scale analysis of the airways of 374
      subjects including a total of 1870 images showed significant correlation with
      lung function and high reproducibility of the measurements.

PMID- 24579153
TI  - Heterogeneity wavelet kinetics from DCE-MRI for classifying gene expression based
      breast cancer recurrence risk.
AB  - Breast tumors are heterogeneous lesions. Intra-tumor heterogeneity presents a
      major challenge for cancer diagnosis and treatment. Few studies have worked on
      capturing tumor heterogeneity from imaging. Most studies to date consider
      aggregate measures for tumor characterization. In this work we capture tumor
      heterogeneity by partitioning tumor pixels into subregions and extracting
      heterogeneity wavelet kinetic (HetWave) features from breast dynamic contrast
      enhanced magnetic resonance imaging (DCE-MRI) to obtain the spatiotemporal
      patterns of the wavelet coefficients and contrast agent uptake from each
      partition. Using a genetic algorithm for feature selection, and a logistic
      regression classifier with leave one-out cross validation, we tested our proposed
      HetWave features for the task of classifying breast cancer recurrence risk. The
      classifier based on our features gave an ROC AUC of 0.78, outperforming
      previously proposed kinetic, texture, and spatial enhancement variance features
      which give AUCs of 0.69, 0.64, and 0.65, respectively.

PMID- 24579154
TI  - Multifold Bayesian kernelization in Alzheimer's diagnosis.
AB  - The accurate diagnosis of Alzheimer's Disease (AD) and Mild Cognitive Impairment
      (MCI) is important in early dementia detection and treatment planning. Most of
      current studies formulate the AD diagnosis scenario as a classification problem
      and solve it using various machine learners trained with multi-modal biomarkers.
      However, the diagnosis accuracy is usually constrained by the performance of the
      machine learners as well as the methods of integrating the multi-modal data. In
      this study, we propose a novel diagnosis algorithm, the Multifold Bayesian
      Kernelization (MBK), which models the diagnosis process as a synthesis analysis
      of multi-modal biomarkers. MBK constructs a kernel for each biomarker that
      maximizes the local neighborhood affinity, and further evaluates the contribution
      of each biomarker based on a Bayesian framework. MBK adopts a novel diagnosis
      scheme that could infer the subject's diagnosis by synthesizing the output
      diagnosis probabilities of individual biomarkers. The proposed algorithm,
      validated using multimodal neuroimaging data from the ADNI baseline cohort with
      85 AD, 169 MCI and 77 cognitive normal subjects, achieves significant
      improvements on all diagnosis groups compared to the state-of-the-art methods.

PMID- 24579155
TI  - High-order graph matching based feature selection for Alzheimer's disease
      identification.
AB  - One of the main limitations of l1-norm feature selection is that it focuses on
      estimating the target vector for each sample individually without considering
      relations with other samples. However, it's believed that the geometrical
      relation among target vectors in the training set may provide useful information,
      and it would be natural to expect that the predicted vectors have similar
      geometric relations as the target vectors. To overcome these limitations, we
      formulate this as a graph-matching feature selection problem between a predicted
      graph and a target graph. In the predicted graph a node is represented by
      predicted vector that may describe regional gray matter volume or cortical
      thickness features, and in the target graph a node is represented by target
      vector that include class label and clinical scores. In particular, we devise new
      regularization terms in sparse representation to impose high-order graph matching
      between the target vectors and the predicted ones. Finally, the selected regional
      gray matter volume and cortical thickness features are fused in kernel space for
      classification. Using the ADNI dataset, we evaluate the effectiveness of the
      proposed method and obtain the accuracies of 92.17% and 81.57% in AD and MCI
      classification, respectively.

PMID- 24579156
TI  - Identification of MCI using optimal sparse MAR modeled effective connectivity
      networks.
AB  - Capability of detecting causal or effective connectivity from resting-state
      functional magnetic resonance imaging (R-fMRI) is highly desirable for better
      understanding the cooperative nature of the brain. Effective connectivity
      provides specific dynamic temporal information of R-fMRI time series and reflects
      the directional causal influence of one brain region over another. These causal
      influences among brain regions are normally extracted based on the concept of
      Granger causality. Conventionally, the effective connectivity is inferred using
      multivariate autoregressive (MAR) modeling with default model order q = 1,
      considering low frequency fluctuation of R-fMRI time series. This assumption,
      although reduces the modeling complexity, does not guarantee the best fitting of
      R-fMRI time series at different brain regions. Instead of using the default model
      order, we propose to estimate the optimal model order based upon MAR order
      distribution to better characterize these causal influences at each brain region.
      Due to sparse nature of brain connectivity networks, an orthogonal least square
      (OLS) regression algorithm is incorporated to MAR modeling to minimize spurious
      effective connectivity. Effective connectivity networks inferred using the
      proposed optimal sparse MAR modeling are applied to Mild Cognitive Impairment
      (MCI) identification and obtained promising results, demonstrating the importance
      of using optimal causal relationships between brain regions for neurodegeneration
      disorder identification.

PMID- 24579157
TI  - Sparse scale-space decomposition of volume changes in deformations fields.
AB  - Anatomical changes like brain atrophy or growth are usually not homogeneous in
      space and across spatial scales, since they map differently depending on the
      anatomical structures. Thus, the accurate analysis of volume changes from medical
      images requires to reliably localize and distinguish the spatial changes
      occurring at different scales, from voxel to regional level. We propose here a
      framework for the sparse probabilistic scale-space analysis of volume changes
      encoded by deformations. Our framework is based on the Helmoltz decomposition of
      vector fields. By scale-space analysis of the scalar pressure map associated to
      the irrotational component of the deformation, we robustly identify the areas of
      maximal volume changes, and we define a consistent sparse decomposition of the
      irrotational component. We show the effectiveness of our framework in the
      challenging problem of detecting the progression of tumor growth, and in the
      group-wise analysis of the longitudinal atrophy in Alzheimer's disease.

PMID- 24579158
TI  - Measurement of myelin in the preterm brain: multi-compartment diffusion imaging
      and multi-component T2 relaxometry.
AB  - Measurements of myelination and indicators of myelination status in the preterm
      brain could be predictive of later neurological outcome. Quantitative imaging of
      myelin could thus serve to develop predictive biomarkers; however, accurate
      estimation of myelin content is difficult. In this work we show that measurement
      of the myelin water fraction (MWF) is achievable using widely available pulse
      sequences and state-of-the-art algorithmic modelling of the MR imaging. We show
      results of myelin water fraction measurement at both 30 (4 infants) and 40 (2
      infants) weeks equivalent gestational age (EGA) and show that the spatial pattern
      of myelin is different between these ages. Furthermore we apply a multi-component
      fitting routine to multi-shell diffusion weighted data to show differences in
      neurite density and local spatial arrangement in grey and white matter. Finally
      we combine these results to investigate the relationships between the diffusion
      and myelin measurements to show that MWF in the preterm brain may be measured
      alongside multi-component diffusion characteristics using clinically feasible MR
      sequences.

PMID- 24579159
TI  - Stent shape estimation through a comprehensive interpretation of intravascular
      ultrasound images.
AB  - We present a method for automatic struts detection and stent shape estimation in
      cross-sectional intravascular ultrasound images. A stent shape is first estimated
      through a comprehensive interpretation of the vessel morphology, performed using
      a supervised context-aware multi-class classification scheme. Then, the
      successive strut identification exploits both local appearance and the defined
      stent shape. The method is tested on 589 images obtained from 80 patients,
      achieving a F-measure of 74.1% and an averaged distance between manual and
      automatic struts of 0.10 mm.

PMID- 24579160
TI  - Epileptogenic lesion quantification in MRI using contralateral 3D texture
      comparisons.
AB  - Epilepsy is a disorder of the brain that can lead to acute crisis and temporary
      loss of brain functions. Surgery is used to remove focal lesions that remain
      resistant to treatment. An accurate localization of epileptogenic lesions has a
      strong influence on the outcome of epilepsy surgery. Magnetic resonance imaging
      (MRI) is clinically used for lesion detection and treatment planning, mainly
      through simple visual analysis. However, visual inspection in MRI can be highly
      subjective and subtle 3D structural abnormalities are not always entirely removed
      during surgery. In this paper, we introduce a lesion abnormality score based on
      computerized comparison of the 3D texture properties between brain hemispheres in
      T1 MRI. Overlapping cubic texture blocks extracted from user-defined 3D regions
      of interest (ROI) are expressed in terms of energies of 3D steerable Riesz
      wavelets. The abnormality score is defined as the Hausdorff distance between the
      ROI and its corresponding contralateral region in the brain, both expressed as
      ensembles of blocks in the feature space. A classification based on the proposed
      score allowed an accuracy of 85% with 10 control subjects and 8 patients with
      epileptogenic lesions. The approach therefore constitutes a valuable tool for the
      objective pre-surgical evaluation of patients undergoing epilepsy surgery.

PMID- 24579161
TI  - Statistical shape model to 3D ultrasound registration for spine interventions
      using enhanced local phase features.
AB  - Accurate registration of ultrasound images to statistical shape models is a
      challenging problem in percutaneous spine injection procedures due to the typical
      imaging artifacts inherent to ultrasound. In this paper we propose a robust and
      accurate registration method that matches local phase bone features extracted
      from ultrasound images to a statistical shape model. The local phase information
      for enhancing the bone surfaces is obtained using a gradient energy tensor
      filter, which combines advantages of the monogenic scale-space and Gaussian scale
      space filters, resulting in an improved simultaneous estimation of phase and
      orientation information. A novel statistical shape model was built by separating
      the pose statistics from the shape statistics. This model is then registered to
      the local phase bone surfaces using an iterative expectation maximization
      registration technique. Validation on 96 in vivo clinical scans obtained from
      eight patients resulted in a root mean square registration error of 2 mm (SD: 0.4
      mm), which is below the clinically acceptable threshold of 3.5 mm. The
      improvement achieved in registration accuracy using the new features was also
      significant (p < 0.05) compared to state of the art local phase image processing
      methods.

PMID- 24579162
TI  - Learning-based modeling of endovascular navigation for collaborative robotic
      catheterization.
AB  - Despite rapid growth of robot assisted catheterization in recent years, most
      current platforms are based on master-slave designs with limited operator-robot
      collaborative control and automation. Under this setup, information concerning
      subject specific behavior and context-driven manoeuvre is not re-utilized for
      subsequent intervention. For endovascular catheterization, the robot itself is
      designed with little consideration of underlying skills and associated motion
      patterns. This paper proposes a learning-based approach for generating optimum
      motion trajectories from multiple demonstrations of a catheterization task such
      that it can be used for automating catheter motion within a collaborative
      setting. Motion models are generated from experienced manipulation of a
      catheterization procedure and replicated using a robotic catheter driver to
      assist inexperienced operators. Catheter tip motions of the automated approach
      are compared against the manual training sets for validating the proposed
      framework. The results show significant improvements in the quality of
      catheterization, which facilitate the design of hands-on collaborative robots
      that make full use of the natural skills of the operators.

PMID- 24579163
TI  - Incremental learning with selective memory (ILSM): towards fast prostate
      localization for image guided radiotherapy.
AB  - Image-guided radiotherapy (IGRT) requires fast and accurate localization of
      prostate in treatment CTs, which is challenging due to low tissue contrast and
      large anatomical variations across patients. On the other hand, in IGRT workflow,
      a series of CT images is acquired from the same patient under treatment, which
      contains valuable patient-specific information yet is often neglected by previous
      works. In this paper, we propose a novel learning framework, namely incremental
      learning with selective memory (ILSM), to effectively learn the patient-specific
      appearance characteristics from these patient-specific images. Specifically,
      starting with a population-based discriminative appearance model, ILSM aims to
      "personalize" the model to fit patient-specific appearance characteristics.
      Particularly, the model is personalized with two steps, backward pruning that
      discards obsolete population-based knowledge, and forward learning that
      incorporates patient-specific characteristics. By effectively combining the
      patient-specific characteristics with the general population statistics, the
      incrementally learned appearance model can localize the prostate of the specific
      patient much more accurately. Validated on a large dataset (349 CT scans), our
      method achieved high localization accuracy (DSC approximately 0.87) in 4 seconds.

PMID- 24579164
TI  - A tensor-based population value decomposition to explain rectal toxicity after
      prostate cancer radiotherapy.
AB  - In prostate cancer radiotherapy the association between the dose distribution and
      the occurrence of undesirable side-effects is yet to be revealed. In this work a
      method to perform population analysis by comparing the dose distributions is
      proposed. The method is a tensor-based approach that generalises an existing
      method for 2D images and allows for the highlighting of over irradiated zones
      correlated with rectal bleeding after prostate cancer radiotherapy. Thus, the aim
      is to contribute to the elucidation of the dose patterns correlated with rectal
      toxicity. The method was applied to a cohort of 63 patients and it was able to
      build up a dose pattern characterizing the difference between patients presenting
      rectal bleeding after prostate cancer radiotherapy and those who did not.

PMID- 24579165
TI  - Image-based computational models for TAVI planning: from CT images to implant
      deployment.
AB  - Transcatheter aortic valve implantation (TAVI) is becoming the standard choice of
      care for non-operable patients suffering from severe aortic valve stenosis. As
      there is no direct view or access to the affected anatomy, accurate preoperative
      planning is crucial for a successful outcome. The most important decision during
      planning is selecting the proper implant type and size. Due to the wide variety
      in device sizes and types and non-circular annulus shapes, there is often no
      obvious choice for the specific patient. Most clinicians base their final
      decision on their previous experience. As a first step towards a more predictive
      planning, we propose an integrated method to estimate the aortic apparatus from
      CT images and compute implant deployment. Aortic anatomy, which includes aortic
      root, leaflets and calcifications, is automatically extracted using robust
      modeling and machine learning algorithms. Then, the finite element method is
      employed to calculate the deployment of a TAVI implant inside the patient
      specific aortic anatomy. The anatomical model was evaluated on 198 CT images,
      yielding an accuracy of 1.30 +/- 0.23 mm. In eleven subjects, pre- and post-TAVI
      CT images were available. Errors in predicted implant deployment were of 1.74 +/-
      0.40 mm in average and 1.32 mm in the aortic valve annulus region, which is
      almost three times lower than the average gap of 3 mm between consecutive implant
      sizes. Our framework may thus constitute a surrogate tool for TAVI planning.

PMID- 24579166
TI  - A deep learning architecture for image representation, visual interpretability
      and automated basal-cell carcinoma cancer detection.
AB  - This paper presents and evaluates a deep learning architecture for automated
      basal cell carcinoma cancer detection that integrates (1) image representation
      learning, (2) image classification and (3) result interpretability. A novel
      characteristic of this approach is that it extends the deep learning architecture
      to also include an interpretable layer that highlights the visual patterns that
      contribute to discriminate between cancerous and normal tissues patterns, working
      akin to a digital staining which spotlights image regions important for
      diagnostic decisions. Experimental evaluation was performed on set of 1,417
      images from 308 regions of interest of skin histopathology slides, where the
      presence of absence of basal cell carcinoma needs to be determined. Different
      image representation strategies, including bag of features (BOF), canonical
      (discrete cosine transform (DCT) and Haar-based wavelet transform (Haar)) and
      proposed learned-from-data representations, were evaluated for comparison.
      Experimental results show that the representation learned from a large histology
      image data set has the best overall performance (89.4% in F-measure and 91.4% in
      balanced accuracy), which represents an improvement of around 7% over canonical
      representations and 3% over the best equivalent BOF representation.

PMID- 24579167
TI  - Mitosis detection in breast cancer histology images with deep neural networks.
AB  - We use deep max-pooling convolutional neural networks to detect mitosis in breast
      histology images. The networks are trained to classify each pixel in the images,
      using as context a patch centered on the pixel. Simple postprocessing is then
      applied to the network output. Our approach won the ICPR 2012 mitosis detection
      competition, outperforming other contestants by a significant margin.

PMID- 24579168
TI  - Learning to segment neurons with non-local quality measures.
AB  - Segmentation schemes such as hierarchical region merging or correllation
      clustering rely on edge weights between adjacent (super-)voxels. The quality of
      these edge weights directly affects the quality of the resulting segmentations.
      Unstructured learning methods seek to minimize the classification error on
      individual edges. This ignores that a few local mistakes (tiny boundary gaps) can
      cause catastrophic global segmentation errors. Boundary evidence learning should
      therefore optimize structured quality criteria such as Rand Error or Variation of
      Information. We present the first structured learning scheme using a structured
      loss function; and we introduce a new hierarchical scheme that allows to
      approximately solve the NP hard prediction problem even for huge volume images.
      The value of these contributions is demonstrated on two challenging neural
      circuit reconstruction problems in serial sectioning electron microscopic images
      with billions of voxels. Our contributions lead to a partitioning quality that
      improves over the current state of the art.

PMID- 24579169
TI  - Analysis of trabecular bone microstructure using contour tree connectivity.
AB  - Millions of people worldwide suffer from fragility fractures, which cause
      significant morbidity, financial costs and even mortality. The gold standard to
      quantify structural properties of trabecular bone is based on the morphometric
      parameters obtained from microCT images of clinical bone biopsy specimens. The
      currently used image processing approaches are not able to fully explain the
      variation in bone strength. In this study, we introduce the contour tree
      connectivity (CTC) as a novel morphometric parameter to study trabecular bone
      quality. With CTC, we calculate a new connectivity measure for trabecular bone by
      using contour tree representation of binary images and algebraic graph theory. To
      test our approach, we use trabecular bone biopsies obtained from 55 female
      patients. We study the correlation of CTC with biomechanical test results as well
      as other morphometric parameters obtained from microCT. The results based on our
      dataset show that CTC is the 3rd best predictive feature of ultimate bone
      strength after bone volume fraction and degree of anisotropy.

PMID- 24579170
TI  - Automated separation of binary overlapping trees in low-contrast color retinal
      images.
AB  - While many approaches exist for the automated segmentation of retinal vessels in
      fundus photographs, limited work has focused on the problem of separating the
      arterial from the venous trees. The few existing approaches that do exist for
      separating arteries from veins are local and/or greedy in nature, making them
      susceptible to errors or limiting their applicability to only the very largest
      vessels. In this work, we propose a new, more global, optimization framework for
      separating two overlapping trees within medical images and apply this approach
      for the separation of arteriovenous trees in low-contrast color fundus images. In
      particular, our approach has two stages. The first stage is to generate a vessel
      potential connectivity map (VPCM) consisting of vessel segments and the potential
      connectivity between them. The second stage is to separate the VPCM into multiple
      anatomical trees using a graph-based meta-heuristic algorithm. Based on a graph
      model, the algorithm first uses local knowledge and global constraints of the
      vasculature to generate near-optimal candidate solutions, and then obtains the
      final solution based on global costs. We test the algorithm on 48 low-contrast
      fundus images and the promising results suggest its applicability and robustness.

PMID- 24579171
TI  - Longitudinal modeling of glaucoma progression using 2-dimensional continuous-time
      hidden Markov model.
AB  - We propose a 2D continuous-time Hidden Markov Model (2D CT-HMM) for glaucoma
      progression modeling given longitudinal structural and functional measurements.
      CT-HMM is suitable for modeling longitudinal medical data consisting of visits at
      arbitrary times, and 2D state structure is more appropriate for glaucoma since
      the time courses of functional and structural degeneration are usually different.
      The learned model not only corroborates the clinical findings that structural
      degeneration is more evident than functional degeneration in early glaucoma and
      the opposite is observed in more advanced stages, but also reveals the exact
      stages where the trend reverses. A method to detect time segments of fast
      progression is also proposed. Our results show that this detector can effectively
      identify patients with rapid degeneration. The model and the derived detector can
      be of clinical value for glaucoma monitoring.

PMID- 24579172
TI  - Discriminative data transform for image feature extraction and classification.
AB  - Good feature design is important to achieve effective image classification. This
      paper presents a novel feature design with two main contributions. First, prior
      to computing the feature descriptors, we propose to transform the images with
      learning-based filters to obtain more representative feature descriptors. Second,
      we propose to transform the computed descriptors with another set of learning
      based filters to further improve the classification accuracy. In this way, while
      generic feature descriptors are used, data-adaptive information is integrated
      into the feature extraction process based on the optimization objective to
      enhance the discriminative power of feature descriptors. The feature design is
      applicable to different application domains, and is evaluated on both lung tissue
      classification in high-resolution computed tomography (HRCT) images and apoptosis
      detection in time-lapse phase contrast microscopy image sequences. Both
      experiments show promising performance improvements over the state-of-the-art.

PMID- 24579173
TI  - Automated embryo stage classification in time-lapse microscopy video of early
      human embryo development.
AB  - The accurate and automated measuring of durations of certain human embryo stages
      is important to assess embryo viability and predict its clinical outcomes in in
      vitro fertilization (IVF). In this work, we present a multi-level embryo stage
      classification method to identify the number of cells at every time point of a
      time-lapse microscopy video of early human embryo development. The proposed
      method employs a rich set of hand-crafted and automatically learned embryo
      features for classification and avoids explicit segmentation or tracking of
      individual embryo cells. It was quantitatively evaluated using a total of 389
      human embryo videos, resulting in a 87.92% overall embryo stage classification
      accuracy.

PMID- 24579174
TI  - Automatic grading of nuclear cataracts from slit-lamp lens images using group
      sparsity regression.
AB  - Cataracts, which result from lens opacification, are the leading cause of
      blindness worldwide. Current methods for determining the severity of cataracts
      are based on manual assessments that may be weakened by subjectivity. In this
      work, we propose a system to automatically grade the severity of nuclear
      cataracts from slit-lamp images. We introduce a new feature for cataract grading
      together with a group sparsity-based constraint for linear regression, which
      performs feature selection, parameter selection and regression model training
      simultaneously. In experiments on a large database of 5378 images, our system
      outperforms the state-of-the-art by yielding with respect to clinical grading a
      mean absolute error (epsilon) of 0.336, a 69.0% exact integral agreement ratio
      (R0), a 85.2% decimal grading error < or = 0.5 (Re0.5), and a 98.9% decimal
      grading error < or = 1.0 (Re1.0). Through a more objective grading of cataracts
      using our proposed system, there is potential for better clinical management of
      the disease.

PMID- 24579175
TI  - 3D intraventricular flow mapping from colour Doppler images and wall motion.
AB  - We propose a new method to recover 3D time-resolved velocity vectors within the
      left ventricle (LV) using a combination of multiple registered 3D colour Doppler
      images and LV wall motion. Incorporation of wall motion, calculated from 3D B
      Mode images, and the use of a multi-scale reconstruction framework allow recovery
      of 3D velocity over the entire ventricle, even in regions where there is little
      or no Doppler data. Our method is tested on the LV of a paediatric patient and is
      compared to 2D and 3D flow Magnetic Resonance Imaging (MRI). Use of wall motion
      information increased stroke volume accuracy by 14%, and enabled full 3D velocity
      mapping within the ventricle. Velocity distribution showed good agreement with
      respect to MRI, and vortex formation during diastole was successfully
      reconstructed.

PMID- 24579176
TI  - Myocardial motion estimation combining tissue doppler and B-mode
      echocardiographic images.
AB  - We present a registration framework that combines both tissue Doppler and B-mode
      echocardiographic sequences. The estimated spatiotemporal transform is
      diffeomorphic, and calculated by modeling its corresponding velocity field using
      continuous B-splines. A new cost function using both B-mode image voxel
      intensities and Doppler velocities is also proposed. Registration accuracy was
      evaluated on synthetic data with known ground truth. Results showed that our
      method allows quantifying wall motion with higher accuracy than when using a
      single modality. On patient data, both displacement and velocity curves were
      compared with the ones obtained from widely used commercial software using either
      B-mode images or TDI. Our method demonstrated to be more robust to image noise
      while being independent from the beam angle.

PMID- 24579177
TI  - Joint statistics on cardiac shape and fiber architecture.
AB  - Cardiac fiber architecture plays an important role in electrophysiological and
      mechanical functions of the heart. Yet, its inter-subject variability and more
      particularly, its relationship to the shape of the myocardium, is not fully
      understood. In this paper, we extend the statistical analysis of cardiac fiber
      architecture beyond its description with a fixed average geometry. We study the
      co-variation of fiber architecture with either shape or strain-based information
      by exploring their principal modes of joint variations. We apply our general
      framework to a dataset of 8 ex vivo canine hearts, and find that strain-based
      information appears to correlate best with the fiber architecture. Furthermore,
      compared to current approaches that warp an average atlas to the patient
      geometry, our preliminary results show that joint statistics improves fiber
      synthesis from shape by 8.0%, with cases up to 25.9%. Our experiments also reveal
      evidence on a possible relation between architectural variability and myocardial
      thickness.

PMID- 24579178
TI  - Spatio-temporal dimension reduction of cardiac motion for group-wise analysis and
      statistical testing.
AB  - Given the observed abnormal motion dynamics of patients with heart conditions,
      quantifying cardiac motion in both normal and pathological cases can provide
      useful insights for therapy planning. In order to be able to analyse the motion
      over multiple subjects in a robust manner, it is desirable to represent the
      motion by a low number of parameters. We propose a reduced order cardiac motion
      model, reduced in space through a polyaffine model, and reduced in time by
      statistical model order reduction. The method is applied to a data-set of
      synthetic cases with known ground truth to validate the accuracy of the left
      ventricular motion tracking, and to validate a patient-specific reduced-order
      motion model. Population-based statistics are computed on a set of 15 healthy
      volunteers to obtain separate spatial and temporal bases. Results demonstrate
      that the reduced model can efficiently detect abnormal motion patterns and even
      allowed to retrospectively reveal abnormal unnoticed motion within the control
      subjects.

PMID- 24579179
TI  - Cardiac fiber inpainting using Cartan forms.
AB  - Recent progress in diffusion imaging has lead to in-vivo acquisitions of fiber
      orientation data in the beating heart. Current methods are however limited in
      resolution to a few short-axis slices. For this particular application and others
      where the diffusion volume is subsampled, partial or even damaged, the
      reconstruction of a complete volume can be challenging. To address this problem,
      we present two complementary methods for fiber reconstruction from sparse
      orientation measurements, both of which derive from second-order properties
      related to fiber curvature as described by Maurer-Cartan connection forms. The
      first is an extrinsic partial volume reconstruction method based on principal
      component analysis of the connection forms and is best put to use when dealing
      with highly damaged or sparse data. The second is an intrinsic method based on
      curvilinear interpolation of the connection forms on ellipsoidal shells and is
      advantageous when more slice data becomes available. Using a database of 8
      cardiac rat diffusion tensor images we demonstrate that both methods are able to
      reconstruct complete volumes to good accuracy and lead to low reconstruction
      errors.

PMID- 24579180
TI  - Sequential Monte Carlo tracking for marginal artery segmentation on CT
      angiography by multiple cue fusion.
AB  - In this work we formulate vessel segmentation on contrast-enhanced CT angiogram
      images as a Bayesian tracking problem. To obtain posterior probability estimation
      of vessel location, we employ sequential Monte Carlo tracking and propose a new
      vessel segmentation method by fusing multiple cues extracted from CT images.
      These cues include intensity, vesselness, organ detection, and bridge information
      for poorly enhanced segments from global path minimization. By fusing local and
      global information for vessel tracking, we achieved high accuracy and robustness,
      with significantly improved precision compared to a traditional segmentation
      method (p = 0.0002). Our method was applied to the segmentation of the marginal
      artery of the colon, a small bore vessel of potential importance for colon
      segmentation and CT colonography. Experimental results indicate the effectiveness
      of the proposed method.

PMID- 24579181
TI  - Tracking of carotid arteries in ultrasound images.
AB  - We introduce an automated method for the 3D tracking of carotids acquired as a
      sequence of 2D ultrasound images. The method includes an image stabilization step
      that compensates for the cardiac and respiratory motion of the carotid, and
      tracks the carotid wall via a shape and appearance model trained from
      representative images. Envisaging an application in automatic detection of
      plaques, the algorithm was tested on ultrasound volumes from 4,000 patients and
      its accuracy was evaluated by measuring the distance between the location of more
      than 4,000 carotid plaques and the location of the carotid wall as estimated by
      the proposed algorithm. Results show that the centroids of over 95% of the
      carotid plaques in the dataset were located within 3 mm of the estimated carotid
      wall, indicating the accuracy of the tracking algorithm.

PMID- 24579182
TI  - Studying cerebral vasculature using structure proximity and graph kernels.
AB  - An approach to study population differences in cerebral vasculature is proposed.
      This is done by (1) extending the concept of encoding cerebral blood vessel
      networks as spatial graphs and (2) quantifying graph similarity in a kernel-based
      discriminant classifier setup. We argue that augmenting graph vertices with
      information about their proximity to selected brain structures adds
      discriminative information and consequently leads to a more expressive encoding.
      Using graph-kernels then allows us to quantify graph similarity in a principled
      way. To demonstrate our approach, we assess the hypothesis that gender
      differences manifest as variations in the architecture of cerebral blood vessels,
      an observation that previously had only been tested and confirmed for the Circle
      of Willis. Our results strongly support this hypothesis, i.e, we can demonstrate
      non-trivial, statistically significant deviations from random gender
      classification in a cross-validation setup on 40 healthy patients.

PMID- 24579183
TI  - Carotid artery lumen segmentation in 3D free-hand ultrasound images using surface
      graph cuts.
AB  - We present a new approach for automated segmentation of the carotid lumen
      bifurcation from 3D free-hand ultrasound using a 3D surface graph cut method. The
      method requires only the manual selection of single seed points in the internal,
      external, and common carotid arteries. Subsequently, the centerline between these
      points is automatically traced, and the optimal lumen surface is found around the
      centerline using graph cuts. To refine the result, the latter process was
      iterated. The method was tested on twelve carotid arteries from six subjects
      including three patients with a moderate carotid artery stenosis. Our method
      successfully segmented the lumen in all cases. We obtained an average dice
      overlap with respect to a manual segmentation of 84% for healthy volunteers. For
      the patient data, we obtained a dice overlap of 66.7%.

PMID- 24579184
TI  - Random walks with adaptive cylinder flux based connectivity for vessel
      segmentation.
AB  - In this paper, we present a novel graph-based method for segmenting the whole 3D
      vessel tree structures. Our method exploits a new adaptive cylinder flux (ACF)
      based connectivity framework, which is formulated based on random walks. To avoid
      the shrinking problem of elongated structure, all existing graph-based energy
      optimization methods for vessel segmentation rely on skeleton or ROI extraction.
      As a result, the performance of these vessel segmentation methods then depends
      heavily on the skeleton extraction results. In this paper, with the help of ACF
      based connectivity framework, a global optimal segmentation result can be
      obtained without extracting skeleton or ROI. The classical issues of the graph
      based methods, such as shrinking bias and sensitivity to seed point location, can
      be solved effectively with the proposed method thanks to the connectivity
      framework.

PMID- 24579185
TI  - Spatially constrained random walk approach for accurate estimation of airway wall
      surfaces.
AB  - Assessing airway wall surfaces and the lumen from high resolution computed
      tomography (CT) scans are of great importance for diagnosing pulmonary diseases.
      However, accurately determining inner and outer airway wall surfaces of a
      complete 3-D tree structure can be quite challenging because of its complex
      nature. In this paper, we introduce a computational framework to accurately
      quantify airways through (i) a precise segmentation of the lumen, and (ii) a
      spatially constrained Markov random walk method to estimate the airway walls. Our
      results demonstrate that the proposed airway analysis platform identified the
      inner and outer airway surfaces better than methods commonly used in clinics,
      such as full width at half maximum and phase congruency.

PMID- 24579186
TI  - Interactive retinal vessel extraction by integrating vessel tracing and graph
      search.
AB  - Despite recent advances, automatic blood vessel extraction from low quality
      retina images remains difficult. We propose an interactive approach that enables
      a user to efficiently obtain near perfect vessel segmentation with a few mouse
      clicks. Given two seed points, the approach seeks an optimal path between them by
      minimizing a cost function. In contrast to the Live-Vessel approach, the graph in
      our approach is based on the curve fragments generated with vessel tracing
      instead of individual pixels. This enables our approach to overcome the shortcut
      problem in extracting tortuous vessels and the problem of vessel interference in
      extracting neighboring vessels in minimal-cost path techniques, resulting in less
      user interaction for extracting thin and tortuous vessels from low contrast
      images. It also makes the approach much faster.

PMID- 24579187
TI  - Free-breathing whole-heart coronary MRA: motion compensation integrated into 3D
      cartesian compressed sensing reconstruction.
AB  - Respiratory motion remains a major challenge for whole-heart coronary magnetic
      resonance angiography (CMRA). Recently, iterative reconstruction has been
      augmented with non-rigid motion compensation to correct for the effects of
      respiratory motion. The major challenge of this approach is the estimation of
      dense deformation fields. In this work, the application of such a motion
      compensated reconstruction is proposed for accelerated 3D Cartesian whole-heart
      CMRA. Without the need for extra calibration data or user interaction, the
      nonrigid deformations due to respiratory motion are directly estimated on the
      acquired image data. In-vivo experiments on 14 healthy volunteers were performed
      to compare the proposed method with the result of a navigator-gated reference
      scan. While reducing the acquisition time by one third, the reconstructed images
      resulted in equivalent vessel sharpness of 0.44 +/- 0.06 mm(-1) and 0.45 +/- 0.05
      mm(-1), respectively.

PMID- 24579188
TI  - Deep learning-based feature representation for AD/MCI classification.
AB  - In recent years, there has been a great interest in computer-aided diagnosis of
      Alzheimer's Disease (AD) and its prodromal stage, Mild Cognitive Impairment
      (MCI). Unlike the previous methods that consider simple low-level features such
      as gray matter tissue volumes from MRI, mean signal intensities from PET, in this
      paper, we propose a deep learning-based feature representation with a stacked
      auto-encoder. We believe that there exist latent complicated patterns, e.g., non
      linear relations, inherent in the low-level features. Combining latent
      information with the original low-level features helps build a robust model for
      AD/MCI classification with high diagnostic accuracy. Using the ADNI dataset, we
      conducted experiments showing that the proposed method is 95.9%, 85.0%, and 75.8%
      accurate for AD, MCI, and MCI-converter diagnosis, respectively.

PMID- 24579189
TI  - Enhancing the reproducibility of group analysis with randomized brain
      parcellations.
AB  - Neuroimaging group analyses are used to compare the intersubject variability
      observed in brain organization with behavioural or genetic variables and to
      assess risks factors of brain diseases. The lack of stability and of sensitivity
      of current voxel-based analysis schemes may however lead to non-reproducible
      results. A new approach is introduced to overcome the limitations of standard
      methods, in which active voxels are detected according to a consensus on several
      random parcellations of the brain images, while a permutation test controls the
      false positive risk. Both on syntetic and real data, this approach shows higher
      sensitivity, better recovery and higher reproducibility than standard methods and
      succeeds in detecting a significant association in an imaging-genetic study
      between a genetic variant next to the COMT gene and a region in the left thalamus
      on a functional magnetic resonance imaging contrast.

PMID- 24579190
TI  - Multiple instance learning for classification of dementia in brain MRI.
AB  - Machine learning techniques have been widely used to support the diagnosis of
      neurological diseases such as dementia. Recent approaches utilize local intensity
      patterns within patches to derive voxelwise grading measures of disease. However,
      the relationships among these patches are usually ignored. In addition, there is
      some ambiguity in assigning disease labels to the extracted patches. Not all of
      the patches extracted from patients with dementia are characteristic of
      morphology associated with disease. In this paper, we propose to use a multiple
      instance learning method to address the problem of assigning training labels to
      the patches. In addition, a graph is built for each image to exploit the
      relationships among these patches, which aids the classification work. We
      illustrate the proposed approach in an application for the detection of
      Alzheimer's disease (AD): Using the baseline MR images of 834 subjects from the
      ADNI study, the proposed method can achieve a classification accuracy of 88.8%
      between AD patients and healthy controls, and 69.6% between patients with stable
      Mild Cognitive Impairment (MCI) and progressive MCI. These results compare
      favourably with state-of-the-art classification methods.

PMID- 24579191
TI  - Extracting brain regions from rest fMRI with total-variation constrained
      dictionary learning.
AB  - Spontaneous brain activity reveals mechanisms of brain function and dysfunction.
      Its population-level statistical analysis based on functional images often relies
      on the definition of brain regions that must summarize efficiently the covariance
      structure between the multiple brain networks. In this paper, we extend a network
      discovery approach, namely dictionary learning, to readily extract brain regions.
      To do so, we introduce a new tool drawing from clustering and linear
      decomposition methods by carefully crafting a penalty. Our approach automatically
      extracts regions from rest fMRI that better explain the data and are more stable
      across subjects than reference decomposition or clustering methods.

PMID- 24579192
TI  - Bayesian joint detection-estimation of cerebral vasoreactivity from ASL fMRI
      data.
AB  - Although the study of cerebral vasoreactivity using fMRI is mainly conducted
      through the BOLD fMRI modality, owing to its relatively high signal-to-noise
      ratio (SNR), ASL fMRI provides a more interpretable measure of cerebral
      vasoreactivity than BOLD fMRI. Still, ASL suffers from a low SNR and is hampered
      by a large amount of physiological noise. The current contribution aims at
      improving the recovery of the vasoreactive component from the ASL signal. To this
      end, a Bayesian hierarchical model is proposed, enabling the recovery of
      perfusion levels as well as fitting their dynamics. On a single-subject ASL real
      data set involving perfusion changes induced by hypercapnia, the approach is
      compared with a classical GLM-based analysis. A better goodness-of-fit is
      achieved, especially in the transitions between baseline and hypercapnia periods.
      Also, perfusion levels are recovered with higher sensitivity and show a better
      contrast between gray- and white matter.

PMID- 24579193
TI  - A new sparse simplex model for brain anatomical and genetic network analysis.
AB  - The Allen Brain Atlas (ABA) database provides comprehensive 3D atlas of gene
      expression in the adult mouse brain for studying the spatial expression patterns
      in the mammalian central nervous system. It is computationally challenging to
      construct the accurate anatomical and genetic networks using the ABA 4D data. In
      this paper, we propose a novel sparse simplex model to accurately construct the
      brain anatomical and genetic networks, which are important to reveal the brain
      spatial expression patterns. Our new approach addresses the shift-invariant and
      parameter tuning problems, which are notorious in the existing network analysis
      methods, such that the proposed model is more suitable for solving practical
      biomedical problems. We validate our new model using the 4D ABA data, and the
      network construction results show the superior performance of the proposed sparse
      simplex model.

PMID- 24579194
TI  - Manifold learning of brain MRIs by deep learning.
AB  - Manifold learning of medical images plays a potentially important role for
      modeling anatomical variability within a population with pplications that include
      segmentation, registration, and prediction of clinical parameters. This paper
      describes a novel method for learning the manifold of 3D brain images that,
      unlike most existing manifold learning methods, does not require the manifold
      space to be locally linear, and does not require a predefined similarity measure
      or a prebuilt proximity graph. Our manifold learning method is based on deep
      learning, a machine learning approach that uses layered networks (called deep
      belief networks, or DBNs) and has received much attention recently in the
      computer vision field due to their success in object recognition tasks. DBNs have
      traditionally been too computationally expensive for application to 3D images due
      to the large number of trainable parameters. Our primary contributions are (1) a
      much more computationally efficient training method for DBNs that makes training
      on 3D medical images with a resolution of up to 128 x 128 x 128 practical, and
      (2) the demonstration that DBNs can learn a low-dimensional manifold of brain
      volumes that detects modes of variations that correlate to demographic and
      disease parameters.

PMID- 24579195
TI  - Multiresolution hierarchical shape models in 3D subcortical brain structures.
AB  - Point distribution models (PDM) are one of the most extended methods to
      characterize the underlying population of set of samples, whose usefulness has
      been demonstrated in a wide variety of applications, including medical imaging.
      However, one important issue remains unsolved: the large number of training
      samples required. This problem becomes critical as the complexity of the problem
      increases, and the modeling of 3D multiobjects/organs represents one of the most
      challenging cases. Based on the 3D wavelet transform, this paper introduces a
      multiresolution hierarchical variant of PDM (MRH-PDM) able to efficiently
      characterize the different inter-object relationships, as well as the particular
      locality of each element separately. The significant advantage of this new method
      over two previous approaches in terms of accuracy has been successfully verified
      for the particular case of 3D subcortical brain structures.

PMID- 24579196
TI  - Unsupervised deep feature learning for deformable registration of MR brain
      images.
AB  - Establishing accurate anatomical correspondences is critical for medical image
      registration. Although many hand-engineered features have been proposed for
      correspondence detection in various registration applications, no features are
      general enough to work well for all image data. Although many learning-based
      methods have been developed to help selection of best features for guiding
      correspondence detection across subjects with large anatomical variations, they
      are often limited by requiring the known correspondences (often presumably
      estimated by certain registration methods) as the ground truth for training. To
      address this limitation, we propose using an unsupervised deep learning approach
      to directly learn the basis filters that can effectively represent all observed
      image patches. Then, the coefficients by these learnt basis filters in
      representing the particular image patch can be regarded as the morphological
      signature for correspondence detection during image registration. Specifically, a
      stacked two-layer convolutional network is constructed to seek for the
      hierarchical representations for each image patch, where the high-level features
      are inferred from the responses of the low-level network. By replacing the hand
      engineered features with our learnt data-adaptive features for image
      registration, we achieve promising registration results, which demonstrates that
      a general approach can be built to improve image registration by using data
      adaptive features through unsupervised deep learning.

PMID- 24579197
TI  - A spatial mixture approach to inferring sub-ROI spatio-temporal patterns from
      rapid event-related fMRI data.
AB  - Previous works investigated a range of spatio-temporal models for fMRI data
      analysis to provide robust determination of functional region-of-interest (ROI).
      We present a novel spatio-temporal fMRI model that is suitable for identifying a
      number of distinct temporal patterns and their spatial support in the voxel
      space. Accordingly, fMRI signals on a single voxel are modeled as a probabilistic
      superposition of those temporal patterns. The spatially varying influence of
      individual patterns is defined in terms of a parameterised function. The temporal
      pattern is characterised by both the underlying hemodynamic response function
      (HRF) and a time series of the individual stimulus-response magnitudes, which
      makes the proposed model particularly suitable for modeling rapid event-related
      fMRI data. Moreover, a parametric approach is adopted to represent the HRFs. The
      resulting methodology is conceptually principled and computationally efficient.
      We first verify the proposed model in a controlled experimental setting using
      synthetic data. The model is further applied to analyzing real fMRI data, with
      focus on functional homogeneity within individual ROIs.

PMID- 24579198
TI  - Group-wise FMRI activation detection on corresponding cortical landmarks.
AB  - Group-wise activation detection in task-based fMRI has been widely used because
      of its robustness to noises and statistical power to deal with variability of
      individual brains. However, current group-wise fMRI activation detection methods
      typically rely on the spatial alignment established by coregistration of
      individual brains' fMRI images into the same template space, which has difficulty
      in dealing with the remarkable anatomic variation of different brains. As a
      consequence, the resulted misalignment among multiple brains could substantially
      degrade the accuracy and specificity of group-wise fMRI activation detection. To
      address these challenges, this paper presents a novel methodology to detect group
      wise fMRI activation based on a publicly released dense map of DTI-derived
      structural cortical landmarks, which possess intrinsic correspondences across
      individuals and populations. The basic idea here is that a first-level general
      linear model (GLM) analysis is performed on fMRI signals of each corresponding
      cortical landmark in each individual brain's own space, and then the single
      subject effect size of the same landmark from a group of subjects are
      statistically integrated and assessed at the group level using the mixed-effects
      model. As a result, the consistently activated cortical landmarks are determined
      and declared group-wisely in response to external block-based stimuli. Our
      experimental results demonstrated that the proposed approach can map meaningful
      group-wise activation patterns on the atlas of cortical landmarks without image
      registration between subjects and spatial smoothing.

PMID- 24579200
TI  - Overlapping replicator dynamics for functional subnetwork identification.
AB  - Functional magnetic resonance imaging (fMRI) has been widely used for inferring
      brain regions that tend to work in tandem and grouping them into subnetworks.
      Despite that certain brain regions are known to interact with multiple
      subnetworks, few existing techniques support identification of subnetworks with
      overlaps. To address this limitation, we propose a novel approach based on
      replicator dynamics that facilitates detection of sparse overlapping subnetworks.
      We refer to our approach as overlapping replicator dynamics (RDOL). On synthetic
      data, we show that RDOL achieves higher accuracy in subnetwork identification
      than state-of-the-art methods. On real data, we demonstrate that RDOL is able to
      identify major functional hubs that are known to serve as communication channels
      between brain regions, in addition to detecting commonly observed functional
      subnetworks. Moreover, we illustrate that knowing the subnetwork overlaps enables
      inference of functional pathways, e.g. from primary sensory areas to the
      integration hubs.

PMID- 24579199
TI  - Predictive models of resting state networks for assessment of altered functional
      connectivity in MCI.
AB  - Due to the difficulties in establishing accurate correspondences of brain network
      nodes across individual subjects, systematic elucidation of possible functional
      connectivity (FC) alterations in mild cognitive impairment (MCI) compared with
      normal controls (NC) is a challenging problem. To address this challenge, in this
      paper, we develop and apply novel predictive models of resting state networks
      (RSNs) learned from multimodal resting state fMRI (R-fMRI) and DTI data to assess
      large-scale FC alterations in MCI. Our rationale is that some RSNs in MCI are
      substantially altered and can hardly be directly compared with those in NC.
      Instead, structural landmarks derived from DTI data are much more consistent and
      correspondent across MCI/NC brains, and therefore can be employed to encode RSNs
      in NC and serve as the predictive models of RSNs for MCI. To derive these
      predictive models, RSNs in NC are constructed by group-wise ICA clustering and
      employed to functionally annotate corresponding structural landmarks. Afterwards,
      these functionally-annotated structural landmarks are predicted in MCI based on
      DTI data and used to assess FC alterations in MCI. Experimental results
      demonstrated that the predictive models of RSNs are effective and can
      comprehensively reveal widespread FC alterations in MCI.

PMID- 24579202
TI  - Modeling dynamic functional information flows on large-scale brain networks.
AB  - Growing evidence from the functional neuroimaging field suggests that human brain
      functions are realized via dynamic functional interactions on large-scale
      structural networks. Even in resting state, functional brain networks exhibit
      remarkable temporal dynamics. However, it has been rarely explored to
      computationally model such dynamic functional information flows on large-scale
      brain networks. In this paper, we present a novel computational framework to
      explore this problem using multimodal resting state fMRI (R-fMRI) and diffusion
      tensor imaging (DTI) data. Basically, recent literature reports including our own
      studies have demonstrated that the resting state brain networks dynamically
      undergo a set of distinct brain states. Within each quasi-stable state,
      functional information flows from one set of structural brain nodes to other sets
      of nodes, which is analogous to the message package routing on the Internet from
      the source node to the destination. Therefore, based on the large-scale
      structural brain networks constructed from DTI data, we employ a dynamic
      programming strategy to infer functional information transition routines on
      structural networks, based on which hub routers that most frequently participate
      in these routines are identified. It is interesting that a majority of those hub
      routers are located within the default mode network (DMN), revealing a possible
      mechanism of the critical functional hub roles played by the DMN in resting
      state. Also, application of this framework on a post trauma stress disorder
      (PTSD) dataset demonstrated interesting difference in hub router distributions
      between PTSD patients and healthy controls.

PMID- 24579203
TI  - [Treatment with Kampo medicine for paranasal sinus disease].

PMID- 24579201
TI  - Genetic clustering on the hippocampal surface for genome-wide association
      studies.
AB  - Imaging genetics aims to discover how variants in the human genome influence
      brain measures derived from images. Genome-wide association scans (GWAS) can
      screen the genome for common differences in our DNA that relate to brain
      measures. In small samples, GWAS has low power as individual gene effects are
      weak and one must also correct for multiple comparisons across the genome and the
      image. Here we extend recent work on genetic clustering of images, to analyze
      surface-based models of anatomy using GWAS. We performed spherical harmonic
      analysis of hippocampal surfaces, automatically extracted from brain MRI scans of
      1254 subjects. We clustered hippocampal surface regions with common genetic
      influences by examining genetic correlations (r(g)) between the normalized
      deformation values at all pairs of surface points. Using genetic correlations to
      cluster surface measures, we were able to boost effect sizes for genetic
      associations, compared to clustering with traditional phenotypic correlations
      using Pearson's r.

PMID- 24579204
TI  - [Discovery of drugs targeting HMGB1-RAGE system].

PMID- 24579205
TI  - [Clinical recommendations to address malnutrition in patients  with end-stage
      liver diseases].

PMID- 24579206
TI  - [Effect of enteral nutrition therapy in patients with  decompensated liver
      cirrhosis].

PMID- 24579207
TI  - [Four-year follow-up of two end-stage hepatitis B cases following transplantation
      of HBsAg-positive donor liver graft].

PMID- 24579208
TI  - Leveraging the plate: reliably restoring volar tilt of distal radius fractures.
AB  - Restoration of volar tilt is critical when performing open reduction and internal
      fixation of distal radius fractures. A reproducible technique is required to
      consistently achieve this goal. A simple technique using the locking plate and an
      electrocautery scratch pad as reduction tools can reliably generate volar tilt.
      This technique can be performed with minimal aid from surgical assistants.

PMID- 24579209
TI  - [Fibrosis-related differential expression and upstream mechanisms of beta
      arrestin in the carbon tetrachloride-induced liver fibrosis mouse model].

PMID- 24579210
TI  - Clinical and economic impact of TENS in patients with chronic low back pain:
      analysis of a nationwide database.
AB  - This study evaluated patients who were given transcutaneous electrical nerve
      stimulation (TENS) compared with a matched group without TENS prior to
      intervention and at 1-year follow-up. Patients who were treated with TENS had
      significantly fewer hospital and clinic visits, used less diagnostic imaging (31
      vs 46 events per 100 patients), had fewer physical therapy visits (94 vs 107),
      and required less back surgery (7.5 vs 9.2 surgeries) than patients receiving
      other treatment modalities. Total annual costs for chronic low back pain patients
      without neurological involvement were lower in TENS patients ($17,957 vs $17,986
      for non-TENS), even when the cost of the device was taken into account.

PMID- 24579211
TI  - Cervical corpectomy with ultra-low-dose rhBMP-2 in high-risk patients: 5-year
      outcomes.
AB  - Twenty-four consecutive patients with cervical spondylosis who were treated with
      cervical corpectomy and recombinant human bone morphogenetic protein-2 (rhBMP-2)
      with standalone anterior instrumentation were evaluated. Mean number of levels
      fused was 2.4. There were significant improvements in visual analog scale neck
      pain and Oswestry Disability Index scores and cervical lordosis. Cervical
      corpectomy with a lower dose of rhBMP-2 was found to be safe and efficacious for
      patients who are at a higher risk for pseudarthrosis.

PMID- 24579212
TI  - [Effects of Cichorium glandulosum Boiss. et Huet. on expression of fibronectin,
      Smad3, IGFBP-rPl, and TGFbeta1 in a liver fibrosis rat model].

PMID- 24579213
TI  - [Protective effects and mechanisms of 1,25(OH)2D3 on diabetes-induced liver
      injury in a streptozotocin-diabetic rat model].

PMID- 24579214
TI  - [Emergence of entecavir genotypic resistance in a nucleoside naive chronic
      hepatitis B patient who had been treated for nearly five years: a case report].

PMID- 24579215
TI  - Current state and use of biological adhesives in orthopedic surgery.
AB  - Bone and tissue adhesives are common and beneficial supplements to standard
      methods of musculoskeletal tissue suture repair. Knowledge and development of
      biologically derived or inspired adhesives useful in orthopedic surgery are
      rapidly advancing. Recent literature demonstrates the increased adjunct or
      primary use of biological adhesives in the repair of musculoskeletal soft
      tissues, chondral fractures, and osteochondral fractures. Adhesives offer more
      benefits and enhancements to tissue healing than current fixation methods afford,
      including improved biocompatibility, resorbability, and non-immunogenicity.
      Further investigation is required to determine the extent of the role that these
      bioadhesives can play in orthopedic surgery. The largest group of biologically
      derived adhesives and sealants is fibrin sealants, which include first- and
      second-generation commercially available fibrin sealants, autologous fibrin
      sealants, and variants. Other groups include gelatin-resorcin aldehydes, protein
      aldehyde systems, collagen-based adhesives, polysaccharide- based adhesives,
      mussel adhesive proteins, and various biologically inspired or biomimetic glues.
      Potential uses include applications in orthopedic-related blood conservation,
      arthroplasty, articular cartilage disorders, sports medicine, spine surgery,
      trauma, and tumors. The development of an adhesive with universal application is
      likely unfeasible, given the unique characteristics of various musculoskeletal
      tissues. However, the literature demonstrates the overall underuse of adhesives
      and indicates the rising probability of the development of a successful variety
      of bioadhesives for use in orthopedic surgery. As a result of reading this
      article, physicians should be able to: 1. Describe the difference between
      adhesives and sealants. 2. Recognize fibrin adhesives commonly used in practice
      today and identify other biological adhesives with rising potential. 3. Analyze
      how fibrin sealants work relative to fibrin and fibrinogen. 4. Identify
      anatomical areas and techniques in which fibrin sealants are used.

PMID- 24579216
TI  - [A case report of sustained virological response with PEG-interferon-alpha-2b in
      a patient with CML and hepatitis C prior fail in ten-year treatment of
      conventional interferon].

PMID- 24579217
TI  - [A case report of hepatic graft versus host disease histologically resembling
      autoimmune hepatitis].

PMID- 24579218
TI  - Acetabular component positioning in primary THA via an anterior, posterolateral,
      or posterolateral-navigated surgical technique.
AB  - The purpose of this study was to compare the acetabular component alignment in
      patients undergoing primary total hip arthroplasty (THA) via 3 surgical
      techniques: direct anterior using intraoperative fluoroscopy, posterolateral
      using an external alignment guide (posterolateral conventional), and
      posterolateral using computer navigation (posterolateral navigated). Two surgeons
      performed the direct, anterior THAs; 2 surgeons performed the posterolateral
      conventional THAs; and 1 surgeon performed the posterolateral-navigated THAs. The
      most recent 110 THAs performed using each approach were reviewed, and Einsel-Bild
      Roentgen analysis software was used to measure the acetabular component abduction
      and anteversion. One-way analysis of variance showed the anterior cohort to have
      a more horizontal alignment of the acetabular component (P,.001); 90.9% of the
      acetabular components in the posterolateral- navigated cohort were within 40
      degrees 610 degrees  and 15 degrees 610 degrees  for both acetabular abduction
      and anteversion, respectively, vs 70% in the posterolateral-conventional
      (P,.001), and 68.2% in the anterior cohort (P,.001). The anterior technique using
      intraoperative fluoroscopy does not improve acetabular positioning compared with
      the conventional, posterolateral technique.

PMID- 24579219
TI  - Early experience with the proximal femoral locking plate.
AB  - The purpose of this study was to evaluate the failure rate of proximal femoral
      locking plates after an initial 2 years of use at a Level I trauma center. This
      retrospective chart review included 13 patients with intertrochanteric or
      peritrochanteric femoral fractures who underwent open reduction and internal
      fixation. Average patient age was 47 years (range, 23-80 years); average follow
      up was 12.7 months (range, 2 weeks to 23 months). Three (23%) patients
      experienced catastrophic failure of the implant. The overall revision rate was
      46% (6 of 13). One patient experienced avascular necrosis and required a planned
      total hip arthroplasty. In the appropriate setting, the proximal femoral locking
      plate can offer stable fixation for fractures involving the proximal femur;
      however, this series highlights the difficulties associated with treating these
      injuries, especially in patients with multiple injuries. Care must be taken to
      avoid varus malalignment and to address metabolic bone dysfunction.

PMID- 24579220
TI  - Arthroscopy during ulnar shortening for idiopathic ulnar impaction syndrome.
AB  - Arthroscopy during ulnar shortening osteotomy for ulnar impaction syndrome is
      subject to debate regarding its clinical usefulness. The purposes of this study
      were to analyze the arthroscopic findings in patients who underwent ulnar
      shortening osteotomy and to assess the role of arthroscopic evaluation during
      osteotomy. Medical records and arthroscopic findings of 50 consecutive patients
      who had been diagnosed with idiopathic ulnar impaction syndrome were
      retrospectively evaluated. Pathologic changes of the articular disk of the
      triangular fibrocartilage complex (TFCC), chondromalacia of the lunate and
      triquetrum, and tears of the lunotriquetral interosseous ligament (LTIL) were
      evaluated during arthroscopy. Palmer's classification was used to classify the
      TFCC lesions. Perforation of the TFCC was observed in 20 patients, and central
      tears were observed in 10. Thirty-eight patients exhibited chondromalacia of the
      lunate, including 4 unstable cartilage flaps. Partial tears of the LTIL were
      detected in 24 patients, including 9 unstable flap tears. In 21 (42%) of 50
      patients, arthroscopic findings were not appropriate to define the disease stage
      with Palmer's original description. Eight wrists exhibited tears or perforations
      of the TFCC without evidence of chondromalacia. Seven patients had an LTIL tear
      without perforation of the TFCC. Lunotriquetral interosseous ligament tears
      without lunate chondromalacia were found in 7 patients. Arthroscopic debridement
      was performed in 23 patients based on the clinical judgment that the procedure
      would help alleviate symptoms postoperatively. Arthroscopy during ulnar
      shortening osteotomy addresses intra-articular pathologies and may be helpful for
      symptom improvement.

PMID- 24579221
TI  - Efficacy of ultrasound-guided intra-articular injections of platelet-rich plasma
      versus hyaluronic acid for hip osteoarthritis.
AB  - Intra-articular injections of platelet-rich plasma (PRP) and hyaluronic acid (HA)
      represent efficacious medical treatments for osteoarthritis (OA), although no
      comparative study on long-term efficacy in hip OA exists. The goals of the
      current study were to compare the clinical efficacy of PRP vs HA at 12 months of
      follow-up in patients with hip OA and evaluate the influence of the type of
      infiltration and patient age, sex, body mass index, and degree of OA on temporal
      clinical evolution. One hundred patients with chronic unilateral symptomatic hip
      OA were consecutively enrolled and randomly assigned to 1 of 2 groups: group A
      received PRP and group B received HA administered via intra-articular ultrasound
      guided injections. Patients were evaluated at baseline and after 1, 3, 6, and 12
      months using the Harris Hip Score (HHS) and visual analog scale (VAS). An overall
      improvement was detected in both groups between 1- and 3-month follow-up. Despite
      a slightly progressive worsening between 6- and 12-month follow-up, the final
      clinical scores remained higher compared with baseline (P<.0005), with no
      significant differences between PRP and HA. Regarding clinical temporal
      evolution, multivariate analysis showed that HHS was not influenced by the type
      of infiltration, patient age, sex, body mass index, or degree of OA, whereas a
      significant association was detected between OA grade IV and VAS evolution
      (P<.0005). Intra-articular injections of PRP are efficacious in terms of
      functional improvement and pain reduction but are not superior to HA in patients
      with symptomatic hip OA at 12-month follow-up.

PMID- 24579222
TI  - Economic viability of geriatric hip fracture centers.
AB  - Management of geriatric hip fractures in a protocol-driven center can improve
      outcomes and reduce costs. Nonetheless, this approach has not spread as broadly
      as the effectiveness data would imply. One possible explanation is that operating
      such a center is not perceived as financially worthwhile. To assess the economic
      viability of dedicated hip fracture centers, the authors built a financial model
      to estimate profit as a function of costs, reimbursement, and patient volume in 3
      settings: an average US hip fracture program, a highly efficient center, and an
      academic hospital without a specific hip fracture program. Results were tested
      with sensitivity analysis. A local market analysis was conducted to assess the
      feasibility of supporting profitable hip fracture centers. The results
      demonstrate that hip fracture treatment only becomes profitable when the annual
      caseload exceeds approximately 72, assuming costs characteristic of a typical US
      hip fracture program. The threshold of profitability is 49 cases per year for
      high-efficiency hip fracture centers and 151 for the urban academic hospital
      under review. The largest determinant of profit is reimbursement, followed by
      costs and volume. In the authors' home market, 168 hospitals offer hip fracture
      care, yet 85% fall below the 72-case threshold. Hip fracture centers can be
      highly profitable through low costs and, especially, high revenues. However, most
      hospitals likely lose money by offering hip fracture care due to inadequate
      volume. Thus, both large and small facilities would benefit financially from the
      consolidation of hip fracture care at dedicated hip fracture centers. Typical US
      cities have adequate volume to support several such centers.

PMID- 24579223
TI  - How frequent is rotational mismatch within 0 degrees +/-10 degrees  in
      kinematically aligned total knee arthroplasty?
AB  - Rotational mismatch of the tibial component on the femoral component within 0
      degrees +/-10 degrees  is associated with better function after mechanically
      aligned total knee arthroplasty (TKA). Kinematically aligned TKA has gained
      interest; however, the percentage of kinematically aligned TKA within 0 degrees
      +/-10 degrees  is unknown. The authors prospectively followed all patients who
      underwent TKA for primary osteoarthritis between December 2011 and April 2012
      (194 patients, 195 knees). Each underwent kinematically aligned TKA with manual
      instruments. Aligning the anteroposterior axis of the tibial component parallel
      to the line that bisects the oval boundary of the lateral tibial condyle set
      internal/external rotation. Removing bone from the posterior femoral condyles
      equal in thickness to the femoral component after correction for cartilage wear
      set internal/external rotation and anteroposterior translation of the femoral
      component. Rotational mismatch of the tibial component on the femoral component
      was determined from a computed tomography scan of the knee. Ninety-seven percent
      of kinematically aligned TKA with fixed-bearing components had a rotational
      mismatch within 0 degrees +/-10 degrees  (overall range, -11 degrees  to 11
      degrees ). This percentage was higher and the range narrower than the 85% of TKA
      within 0 degrees +/-10 degrees  and the -14 degrees  to 16 degrees  range
      reported for mechanically aligned TKA. The use of manual instruments to
      kinematically aligned TKA reliably limited rotational mismatch to within 0
      degrees +/-10 degrees , which has been associated with better function.

PMID- 24579224
TI  - Four- to six-year follow-up of primary THA using contemporary titanium tapered
      stems.
AB  - Tapered cementless femoral components have been used in total hip arthroplasty
      constructs for more than 20 years. In the past 5 to 10 years, these stems have
      gained popularity in the United States. The purpose of this study was to evaluate
      the results of the authors' initial experience using a contemporary tapered,
      proximally porous-coated, titanium femoral component at 4 to 6 years of follow
      up. Eighty-eight patients underwent 100 total hip arthroplasties using the Summit
      stem (DePuy, Warsaw, Indiana) and a cementless acetabular component. Average age
      at the time of surgery was 61.6 years. Patients were prospectively followed for 4
      to 6 years or until death. Patients were evaluated clinically using Harris Hip
      Scores and the need for revision. Radiographs were evaluated for femoral
      loosening and osteolysis. At final follow-up, no hips had been revised for
      femoral or acetabular loosening. Two hips required revision for dislocation and 1
      for early femoral fracture. Bony ingrowth was seen in all but 2 femoral
      components. There was 1 instance of proximal femoral osteolysis and none distally
      on radiographs (cross-linked polyethylene was used in 73% of cases). There were 2
      cases of severe stress shielding. One percent of cases had an early fracture (too
      tight) and 1% subsided without ingrowth (too loose). One patient reported
      significant thigh pain that did not limit activity. At final follow-up, the
      Summit femoral component demonstrated durable results at 4 to 6 years. Stability
      of the implant without femoral fracture is paramount.

PMID- 24579225
TI  - Bloodless surgery by a regional intraarterial tourniquet during primary and
      revision THA.
AB  - Primary total hip arthroplasty (THA) and revision THA are associated with blood
      loss that can be significant. The purpose of this retrospective study was to
      compare the efficacy of intra-arterial occlusive balloons in reducing blood loss
      during primary and revision THA. Twelve patients (Jehovah's Witnesses) scheduled
      for a primary (n=6) or revision (n=6) THA who refused blood transfusions were
      compared with 48 control-matched patients (primary THA, n=24; revision THA,
      n=24). All Jehovah's Witnesses received an intra-arterial balloon preoperatively,
      and all control patients underwent conventional surgery. Intraoperatively,
      balloons were periodically inflated to reduce blood loss and deflated to prevent
      limb ischemia. Endpoints for the study were estimated blood loss, perioperative
      hemoglobin, mean hospital stay, mean operative time, amount of intraoperative
      fluid or blood administered, and complications. None of the patients with an
      occlusive balloon received blood, whereas the primary THA group received an
      average of 0.6 units (P=.08) and the revision THA group received an average of
      1.9 units (P=.02). Estimated blood loss was significantly decreased in the
      balloon group compared with the primary THA group (145 vs 402 mL, respectively;
      P<.01) and the revision THA group (333 vs 767 mL, respectively; P<.01). No
      complications were associated with the intra-arterial balloons. All patients
      showed a significant reduction in hemoglobin immediately postoperatively compared
      with preoperative values. No statistically significant differences existed in the
      amount of fluids given intraoperatively or the mean hospital stay among all
      groups. Temporary internal tourniquets used as an adjuvant to surgery
      significantly reduce intraoperative blood loss during primary and revision THA.

PMID- 24579226
TI  - Outcomes in patients with minimal back pain undergoing prophylactic lumbar fusion
      for iatrogenic instability.
AB  - For most patients undergoing lumbar fusion, back pain is a substantial part of
      their preoperative symptomatology. Occasionally, there are patients with minimal
      back pain in whom the extent of decompression required to treat leg symptoms
      requires a concomitant fusion to prevent postoperative instability. Although
      these patients may obtain relief of their leg pain, an additional concern is
      whether they will develop increased back pain after fusion. This study's primary
      cohort comprised 1144 patients with complete preoperative and 2-year
      postoperative data including the Oswestry Disability Index (ODI), Short Form 36
      (SF-36), and numeric rating scales (NRS) for back and leg pain. Thirty-nine
      patients with a preoperative back pain score of 3 or less were identified.
      Propensity scoring was used to match these patients to patients with moderate
      back pain (NRS 4-6) and severe back pain (NRS 7-10) based on demographics,
      baseline health-related quality of life, and surgical characteristics, resulting
      in 35 patients in each group. Paired t tests were used to determine within-group
      differences, and analysis of variance was used to determine between-group
      differences. A statistically significant improvement occurred in ODI, SF-36
      Physical Component Summary, and NRS leg pain scores from preoperatively to 2
      years postoperatively (P<.0001) within all groups; and a statistically
      significant improvement occurred in back pain scores in the moderate and severe
      back pain groups. No statistically significant change occurred in back pain from
      preoperatively to 2 years postoperatively (P=.528) in the minimal back pain
      group. Patients undergoing lumbar fusion for predominant leg pain with minimal
      back pain had acceptable outcomes, with no increase in back pain postoperatively.

PMID- 24579227
TI  - Clinical comparison of THA with a standard-length or short femoral component.
AB  - The purposes of this 2-part study were to determine whether reduced distal
      femoral component geometry allows for routinely larger component sizes to be used
      and whether clinical or radiographic outcomes differ between total hip
      arthroplasty (THA) patients treated with either standard-length or short femoral
      components. Femoral component size and ongrowth surface area were retrospectively
      compared in a group of bilateral THA patients that had both a standard-length
      component and a contralateral short component. Then, clinical and radiographic
      outcomes were compared between matched groups of THA patients that had either a
      standard-length or short femoral component. The use of the short component
      resulted in a significantly larger femoral component size being used (P=.01), and
      the potential ongrowth surface area was significantly larger for the short
      component than for the standard component (median, 36.69 vs 35.55 cm2; P=.02). In
      the matched-pairs analysis, no group differences were noted in modified Harris
      Hip Scores (P=.43) or femoral component subsidence (P=.35), but there was a
      significantly greater prevalence of radiolucent lines in Gruen zone 8 with the
      short component (P=.008). The use of a short femoral component was associated
      with consistently larger component sizes being used, which corresponded with a
      larger potential ongrowth surface area. Short-term clinical and radiographic
      outcomes did not differ between standard-length and short femoral components.
      Studies are necessary to determine whether the increased proximal ongrowth
      surface area may result in improved long-term fixation or, on the contrary, may
      increase the risk of periprosthetic fracture.

PMID- 24579228
TI  - Arthroscopic lysis of adhesions for stiff total knee arthroplasty.
AB  - The goal of this study was to evaluate the efficacy of arthroscopic lysis of
      adhesions after total knee arthroplasty (TKA) in improving range of motion (ROM)
      and providing an improvement in knee function. The authors retrospectively
      examined 19 patients who underwent arthroscopic lysis of adhesions following TKA
      due to poor ROM. The criterion for lysis was the inability to flex to 90 degrees 
      at 3 months. All patients were followed for at least 2 years after lysis. Patient
      demographics, postoperative and follow-up ROM,number of prior surgeries, Knee
      Society Scores, and Western Ontario and McMaster Universities Arthritis Index
      (WOMAC) functional scores were collected. Average ROM increased from 75.37
      degrees  preoperatively to 98.95 degrees  postoperatively. The authors found an
      association between preoperative knee score and change in ROM between pre
      arthroscopic lysis and ROM at final follow-up (P=.0188). When the authors
      examined the relationship between patient body mass index (BMI) and change in
      ROM,they found that patients with a BMI higher than 30 kg/m2 had a change of
      26.44 degrees  compared with patients with a BMI lower than 30 kg/m2, who had a
      change of only 8.75 degrees . A strong association was found between patient
      height and change in ROM and final ROM achieved (P=.0062 and .0032,
      respectively). The authors report a successful outcome among study patients.
      Furthermore, they found an association between patient height, BMI, and
      preoperative knee score and the improvement achieved after arthroscopic lysis of
      adhesions following TKA. The current study's results are comparable with those of
      published results. The authors recommend arthroscopic lysis of adhesions as a
      treatment option for stiff knees after TKA that fails after at least 3 months of
      nonoperative treatment.

PMID- 24579229
TI  - Posttraumatic arthritis from gunshot injuries to the hip requiring a primary THA.
AB  - Gunshot injuries to the hip can be devastating, leading to posttraumatic
      arthritis and presenting a surgical challenge at the time of total hip
      arthroplasty (THA) due to the presence of metallic fragments and damaged soft
      tissues. However, there are few reports of gunshot-related posttraumatic
      arthritis. The purpose of this study was to describe the features and report the
      early outcomes of THA in 4 patients who developed posttraumatic arthritis from
      gunshot injuries to their hips 2, 10, 18, and 26 years after their initial
      injury, respectively. All 4 patients underwent successful THA without
      complications. None of the patients had undergone a revision procedure at a mean
      26-month (range, 12-48 months) follow-up. The authors believe that primary THA is
      a safe and effective procedure to reduce pain and improve function for gunshot
      related posttraumatic arthritis in patients in whom nonoperative management
      failed.

PMID- 24579230
TI  - Proximal humeral nonunion treated with an intramedullary tantalum cylinder.
AB  - Nonunion is uncommon after proximal humerus fracture surgery. There is no
      agreement about preferred method of treatment. Traditional approaches have
      included laterally based locking plates, autogenous grafting, and endosteal
      support to provide improved biomechanical stability. Open reduction and internal
      fixation (ORIF) of proximal humeral nonunion has been performed with various
      methods, including blade plates and bone grafting, as well as intramedullary
      support with autologous or allogenic grafts. Both malunion and nonunion have
      occurred after ORIF with locking plates. Endosteal support in the form of a
      fibular allograft incorporated into the locking plate construct can increase
      mechanical stability in selected cases. An ideal implant for proximal humeral
      nonunion provides medial column mechanical support and osteoconductive and
      osteoinductive properties. Porous intramedullary tantalum metal may play a role
      in nonunion surgery as an alternative to fibular allograft because of its
      versatility of use and salutary biological effects. It offers many material
      advantages for use in nonunion surgery. Tantalum is extensively porous (75%-80%),
      has a stiffness close to that of native bone, and offers the possibility of being
      a carrier for osteoinductive materials. It may also be suitable for patients who
      refuse allograft material. This article describes a 65-year-old woman with
      recalcitrant proximal humeral nonunion who was successfully treated with revision
      ORIF with intramedullary tantalum cylinder augmentation with a lateral-based
      locking plate and autogenous cancellous bone grafting. At 5-year follow-up, she
      had excellent motion and clinical and radiographic union.

PMID- 24579232
TI  - Pelvic deformity secondary to tensor fascia lata tightness associated with
      desmoid tumor.
AB  - The iliotibial band is a thick, condensed fascia that, when contracted, leads to
      a hip flexion, abduction, and external rotation contracture in addition to other
      joint contractures. Iliotibial band tightness occurs secondary to iliotibial band
      friction syndrome, which commonly occurs at the lateral femoral epicondylar
      region. However, a proximal cause of iliotibial band/tensor fascia lata friction
      syndrome leading to a secondary hip contracture is swelling around the hip; this
      swelling being a desmoid tumor has not been explicitly described in the
      literature. The authors present a rare case of a hip contracture in a 28-year-old
      active man who presented with a functionally disabling hip flexion contracture of
      20 degrees  with further flexion possible up to 130 degrees , a 45 degrees 
      abduction contracture, and a 20 degrees  external rotation contracture with
      further rotation possible up to 40 degrees  with a bony hard swelling in the left
      gluteal region. Ober's test was positive. Opposite hip and spine examinations
      were normal. The goals of treatment were to establish the causality between the 2
      and to diagnose the etiology of the gluteal mass. Radiographs were normal, with
      only a pelvic obliquity evident. Magnetic resonance imaging revealed an extra
      articular mass abutting the iliac blade. Histopathology confirmed the mass to be
      a desmoid tumor in the left gluteal region. A wide surgical excision of the mass
      was performed with negative margins; no postoperative radiotherapy was
      administered. After rigorous physiotherapy, the hip deformity disappeared at 6
      months and there was no evidence of recurrence at 2.5-year follow-up, with the
      patient able to sit cross-legged and squat.

PMID- 24579231
TI  - Identical osteochondritis dissecans lesions of the knee in sets of monozygotic
      twins.
AB  - Osteochondritis dissecans (OCD) is a focal, idiopathic alteration of subchondral
      bone structure with the risk for secondary damage to adjacent articular cartilage
      and the development of premature osteoarthritis. The exact etiology of OCD is
      unknown, although repetitive microtrauma and vascular insufficiency have been
      previously described. A genetic predisposition has been suggested, but the
      existing evidence is sparse. There are multiple case reports of twins and
      siblings with OCD and a few large family series in the literature, promoting the
      theory that OCD may have a genetic component to its etiology. This article
      describes 2 sets of monozygotic twins presenting concurrently with OCD of their
      dominant knees, offering further support for a genetic component to the etiology
      of OCD. Interestingly, in both sets of twins, 1 was left-handed and 1 was right
      handed. Both sets of twins had simultaneous presentations and clinical courses,
      lending support to a genetic element to OCD. The development of the OCD lesion in
      the dominant knee of each patient suggests an environmental influence, perhaps
      due to repetitive microtrauma and overuse. Recently, a genome-wide linkage study
      identified a prime candidate locus for OCD. However, despite the suggested
      association, genetic and developmental factors in the development of OCD remain
      relatively unstudied. The authors believe monozygotic twins provide an excellent
      clinical opportunity for future examination of the role of familial inheritance
      in the etiology of OCD.

PMID- 24579233
TI  - [Primary liver paraganglioma: a case report].

PMID- 24579234
TI  - [Hepatocellular carcinoma risk and hepatitis B virus mutations].

PMID- 24579235
TI  - [Update of FOXP3 and chronic liver diseases].

PMID- 24579236
TI  - [Recent progress in research of biomarkers of acute kidney injury  in liver
      cirrhosis].

PMID- 24579237
TI  - [A brief report on the 5th National Congress of Fatty Liver Disease and 2013
      Frontiers Medical Forum in China].

PMID- 24579238
TI  - Epidemiology of MDR-TB in a Belgian infectious diseases unit: a 15 years review.
AB  - INTRODUCTION: For the last 20 years the world has seen the emergence of a growing
      epidemic of MDR-TB, followed by the appearance of XDR-TB. Both require longer,
      more expensive and more toxic treatments. MDR-TB and especially XDR-TB are
      associated with a lower cure rate than non MDR-TB. MATERIALS AND METHODS: We
      reviewed retrospectively all cases of MDR-and XDR-TB managed at St Pierre
      University Hospital between 1996 and 2010. Epidemiological, clinical,
      bacteriological, treatment, follow up and outcome were collected and analysed.
      RESULTS: We recorded 73 instances of MDR-TB and 11 XDR-TB for a total of 78
      patients. All but 4 patients were of non Belgian origin. 10 patients were co
      infected with HIV. A median of 4 active drugs (1-5) were used for a median of 448
      days (329-616). 41 MDR-TB (56%) and 1 XDR-TB (1%) were considered as cured and 20
      are still on treatment. Since 2007, increasing resistance to second line
      injectable drugs, fluoroquinolones and even linezolid (1 case) is observed.
      Extensive resistance was mainly found in patients who had previously been
      mismanaged with second line agents. CONCLUSIONS: This study illustrates the
      growing epidemic of MDR and XDR-TB, it emphasizes the importance of proper
      diagnosis and adequate management of TB in patients at risk for resistance and
      stresses the need for new therapies.

PMID- 24579239
TI  - COPD awareness survey: do Belgian pulmonary physicians comply with the GOLD
      guidelines 2010?
AB  - Chronic Obstructive Pulmonary Disease (COPD) is underestimated, underdiagnosed
      and often under-treated in the general population. A survey of 17 structured
      questions, delivered to all Belgian pulmonary physicians (PPs) (116 responses),
      evaluated diagnosis and treatment strategies in accordance with the Global
      Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines 2010 and
      assessed opinions about the importance of diurnal variation of COPD symptoms. All
      COPD diagnoses (37% new cases) were spirometry confirmed. Main diagnostic
      parameters were symptoms (99%), external risk factors (99%), clinical examination
      (97%), exacerbations (96%) and patient mobility (96%). FEV1 (forced expiratory
      volume in 1s) (97%) or FEV1/FVC (ratio of FEV1 to forced vital capacity) (93%)
      were used most to assess diagnosis and severity. The 3 most important therapeutic
      objectives were symptom relief, preventing exacerbations, and improving quality
      of life; if these were not reached, the preferred strategy (60% of PPs) was
      adding another medication. Treatment strategies varied with COPD stage: short
      acting beta2-agonists (90%) and short-acting anti-cholinergics (59%) were used
      for GOLD I disease, whereas for higher stages long-acting beta2-agonists (36-48%)
      and long-acting anti-cholinergics (79%) were given with inhaled corticosteroids
      (21-67%). Symptoms were perceived to vary throughout the day, affecting quality
      of life (97%) and mobility (89%). In particular, respiratory symptoms were more
      severe in the morning (51-92%), leading PPs to adapt treatment (69%). This survey
      demonstrated that management of COPD by PPs in Belgium is generally in line with
      the GOLD guidelines 2010 and that they perceive morning symptoms as being
      frequent and having an impact on patient's life.

PMID- 24579240
TI  - Prevalence of Bordetella holmesii and Bordetella bronchiseptica in respiratory
      tract samples from Belgian patients with pertussis-like symptoms by sensitive
      culture method and mass spectrometry.
AB  - Insertion sequences IS481 and IS1001 are targets for molecular detection of
      respectively Bordetella pertussis and Bordetella parapertussis. There is a
      raising concern about specificity of these targets due to sequence similarity
      with Bordetella holmesii and Bordetella bronchiseptica. The likelihood of false
      (para)pertussis diagnoses should be correlated with the prevalence of these
      organisms in the respiratory tract (RT). From October 2010 until September 2011,
      2,207 RT samples were submitted to the Belgian reference laboratory for pertussis
      diagnosis. End-point IS481/IS 1001 PCR and culture were performed for B.
      pertussis and B. parapertussis. We developed a sensitive culture method followed
      by screening with matrix-assisted laser desorption/ionisation- time of flight
      mass spectrometry (MALDI-TOF MS) to look for B. holmesii and B. bronchiseptica in
      our samples,. Only one B. bronchiseptica and no B. holmesii were detected in RT
      samples from Belgian patients with pertussis-like symptoms.

PMID- 24579241
TI  - Barriers to liver transplantation in HIV infected patients.
AB  - OBJECTIVES: Liver disease is one of the most frequent causes of non AIDS related
      deaths in HIV patients and transplantation has become a therapeutic option. In
      spite of this progress, no liver transplantation has ever been recorded for the
      patients of the Brussels Saint-Pierre HIV Cohort. The aim of this study is to
      identify the barriers to liver transplantation in HIV patients that arise in our
      practice. METHODS: All patients enrolled in the Brussels Saint-Pierre HIV Cohort
      presenting a theoretical indication for liver transplantation, as recommended by
      the AASLD, between 01/01/2002 and 01/07/2010 were considered. The reasons for not
      retaining these patients as candidates for liver transplantation were classified
      as HIV or non-HIV related. RESULTS: Nineteen patients were identified. All
      patients presented an HBV and/or HCV co-infection. Indication for liver
      transplantation was based on first severe complication of cirrhosis for 15
      patients, hepatocellular carcinoma fulfilling the Milan criteria for 2 and
      chronic liver failure for 2 others. Three patients could have been
      transplantation candidates but only one was enlisted and died prior to
      transplantation whilst alternative treatments were chosen for the remaining two.
      Among the non candidates, 5 couldn't be enlisted for HIV-related reasons, 3 for
      non HIV related reasons and 8 on multifactorial grounds; non adherence to
      treatment, alcohol abuse, psychiatric disease and hepatotoxicities playing key
      roles. Eleven patients died, all within 12 months of their first major
      complication of cirrhosis. CONCLUSIONS: The undeniable medical progress that
      liver transplantation represents for HIV-infected individuals is, in practise,
      limited; only a minority of patients with an indication of liver transplant will
      fulfill the necessary criteria for enlistment. General awareness of this issue
      and early referral are essential to optimize pre-transplant management and
      increase the number of HIV patients developing ESLD that will be able to benefit
      from this cure.

PMID- 24579243
TI  - Plasma level monitoring of the major metabolites of diacetylmorphine (heroin) by
      the "chasing the dragon" route in severe heroin addicts.
AB  - The objective of the present study was to verify if severe physical health
      problems frequently encountered in heroin addicts and the concomitant use of
      alcohol and legal or illegal drugs other than heroin influenced the
      pharmacokinetics of the major metabolites of heroin. We conducted a 90 minutes
      follow-up of the plasma concentrations of the pharmaceutical heroin, named
      diacetylmorphine (DAM), in patients recruited in a DAM assisted treatment centre.
      TADAM (Traitement Assiste par DiAcetylMorphine) aimed to compare the efficacy of
      heroin-assisted treatment (HAT) compared with methadone maintenance treatment
      (MMT) for heroin users considered as treatment resistant patients and who have
      severe physical and mental health problems. Eleven patients were recruited. Blood
      samples were collected at baseline and 15, 45 and 90 minutes after DAM
      administration. All patients received DAM by the "chasing the dragon" route.
      Plasma samples were analyzed by a previously described ultra-high pressure liquid
      chromatography coupled to tandem mass spectrometry (UHPLC/MS-MS) method. A
      principal component analysis (PCA) was performed and 8 metabolite concentrations
      ratios were calculated to evaluate the influence of various factors (DAM dose,
      patient pathologies, concomitant use of medications, methadone, street heroin,
      alcohol and cocaine) on heroin metabolite pharmacokinetics. It seemed to be not
      affected by the DAM dose, patient pathologies and the concomitant use of
      medications, methadone, street heroin and alcohol. Cocaine use was the only
      parameter which showed differences in heroin pharmacokinetics.

PMID- 24579242
TI  - Drug-related admissions due to interaction with an old drug, lithium.
AB  - Lithium is one of the oldest psychotropic drugs with a well-known narrow
      therapeutic range and the drugs that interact with lithium elimination are well
      established. However, patients are still admitted to the emergency department
      with lithium toxicity due to often overlooked interactions with concomitant
      drugs. We report on two patients, admitted to the emergency department, with
      lithium toxicity. One patient presented with aphasia and ataxia, showing moderate
      toxicity. The other was referred due to coma, illustrating severe lithium
      toxicity. In both cases, a non-steroidal anti-inflammatory drug was the
      underlying cause. We highlight the mechanism of this drug-drug interaction and
      underline the need for thoughtful use of other medications in patients taking
      lithium. Special attention has to be paid for the non-steroidal antiinflammatory
      drugs due to the low threshold of prescribing them for the control of acute pain
      and its availability as free over-the-counter drugs.

PMID- 24579244
TI  - Invasive aspergillosis in patients with cirrhosis, a case report and review of
      the last 10 years.
AB  - BACKGROUND: Untreated invasive aspergillosis (IA) is lethal, yet diagnosis is
      often delayed. Recognising the risk factors can lead to earlier diagnosis. We
      present a case of an invasive pulmonary aspergillosis in a patient with
      cirrhosis, who had been treated with corticosteroids for 2.5 weeks for alcoholic
      hepatitis. He was successfully treated with liposomal amphotericin B and
      caspofungin (first in combination, then caspofungin monotherapy). PURPOSE: To
      evaluate the role of aspergillosis in cirrhosis. METHODS: A literature search on
      aspergillosis in cirrhosis and liver failure patients was conducted in
      PubMed/Medline (2002-dec 2012), according to pre-set selection criteria. RESULTS:
      20 out of 330 articles were retrieved, representing 43 patients with cirrhosis
      and/or liver failure who had an aspergillosis infection. Most Aspergillus (A.)
      infections were due to A. fumigatus and the lungs were the most frequent organ
      involved (42/43). 58% of the patients used steroids and mortality was 53.5%. The
      most frequent used antifungal was caspofungin. DISCUSSION: Diagnosis of IA is
      difficult and there might be a delay in diagnosis since cirrhosis is not
      recognised as one of the classical risk factors. Mortality was 53.5%, but this is
      lower than in previous decades. Since voriconazole is hepatotoxic, treatment with
      caspofungin and/or amphotericin is preferable. CONCLUSION: Early recognition of
      aspergillosis in a cirrhosis/liver failure patient is crucial and should prompt
      direct treatment.

PMID- 24579246
TI  - A neonate with a meningomyelocele complicated by Aeromonas caviae
      ventriculoperitoneal shunt infection.
AB  - We report on a newborn girl with a Aeromonas caviae shunt infection and
      meningitis after insertion of a ventriculoperitoneal shunt and surgical repair of
      a meningomyelocele in one procedure. This pathogen has never been reported,
      related to ventriculoperitoneal shunt infections. Beside the need for surgical
      revision of the shunt because of shunt obstruction and septa formation in the
      ventricles, the clinical outcome was good with intravenous cefotaxime therapy.

PMID- 24579245
TI  - Successful non-surgical treatment of endocarditis caused by Staphylococcus
      haemolyticus following transcatheter aortic valve implantation (TAVI).
AB  - We describe a case of a 79-year-old male patient with severe aortic stenosis who
      underwent transcatheter aortic valve implantation (TAVI) at our institution. He
      presented at the emergency department with dyspnea and fatigue 7 months after
      implantation. The diagnosis of early prosthetic valve endocarditis (PVE) caused
      by Staphylococcus haemolyticus was made by transesophageal echocardiography (TEE)
      and multiple positive blood cultures. Since our patient was considered inoperable
      due to a history of coronary artery bypass graft (CABG) surgery with patent
      bypasses, high peri-operative mortality including renal failure and a poor
      general prognosis, surgical removal of the valve was not an option. The patient
      was successfully treated with antibiotic therapy.

PMID- 24579248
TI  - A rare cause of ascites: myxoedema ascites.
AB  - The case report describes an 88-year-old patient who presented with new-onset
      ascites. After excluding frequent causes of ascites, he was diagnosed with
      myxoedema ascites. Myxoedema ascites is rare. Analysis of ascitic fluid shows a
      high serum-ascites albumin gradient and a high protein level. Myxoedema ascites
      resolves completely after starting thyroid hormone replacement therapy.

PMID- 24579247
TI  - A forgotten disease in a returning traveler from Thailand.
AB  - Cutaneous diphteria is a forgotten disease. We must consider this in our
      differential diagnosis, not only when a patient presents with a cutaneous ulcer
      and has travelled to tropical areas, but also in patients who subsist in low
      socio-economic conditions, especially in homeless people and people with a
      history of alcohol or drug abuse. Vigilance for this forgotten disease is
      warranted because most physicians in developed countries have never seen one
      case. In an era of increasing globalisation, we might see more cases in the
      future. We report a case of a foot infection with a non toxigenic C. diptheriae
      biovar gravis in a 16 year old girl, who has travelled to Thailand.

PMID- 24579250
TI  - Acute oxalate nephropathy after renal transplantation.

PMID- 24579251
TI  - Dutch borders impervious to ticks or Lyme borreliosis underreporting in Belgium.

PMID- 24579249
TI  - Pathologic complete remission of malignant pleural mesothelioma after combined
      modality treatment: a case report.
AB  - A 50-year-old patient with malignant pleural mesothelioma (epithelial subtype,
      clinically staged cT1bN0M0) underwent a combined modality treatment, including
      induction chemotherapy, followed by extrapleural pneumonectomy (EPP) and radical
      radiotherapy. After pathologic examination of the surgical specimen, a complete
      remission (pT0N0) was observed. The complete disappearance of solid tumour tissue
      after induction chemotherapy is a rarely observed and documented finding in the
      combined modality treatment of malignant pleural mesothelioma. The real
      prognostic value of the pathologic complete remission of a malignant pleural
      mesothelioma definitely needs to be further evaluated in a larger series of
      patients.

PMID- 24579253
TI  - The FDI World Dental Federation Congress.

PMID- 24579252
TI  - A Leser-Trelat sign indicating multiple gastrointestinal neoplasia.

PMID- 24579254
TI  - Random thoughts on an autumn evening.

PMID- 24579255
TI  - A case report of developmentally missing mental foramen.
AB  - The inferior alveolar nerve is the mandibular division of the trigeminal nerve.
      Studies have documented variations in the course and branching pattern of the
      nerve. Here the author reports a case of developmentally missing mental foramen
      in an individual with normal sensory function. Identification of variations in
      the nerve pathway is essential for treatment planning in the area.

PMID- 24579256
TI  - Abundance.

PMID- 24579257
TI  - Cementation: methods and materials. Part two.
AB  - This is a review of the literature of the last 21 years about cementing or luting
      indirect restorations to tooth structure. Recommendations are made as to the
      surface preparation of precious metals, non-precious metals, indirect composite
      materials, and all available porcelain materials including feldspathic, luecite
      reinforced, lithium di-silicate, slip cast aluminum oxide, densely sintered
      aluminum oxide, and zirconia prior to luting. Using data from a variety of
      sources, product categories of materials and various bonding materials and
      procedures are ranked according to their bond strength and durability.

PMID- 24579258
TI  - Sheets of ice.

PMID- 24579259
TI  - Infection control, oral health in pregnancy.

PMID- 24579260
TI  - Intentions.

PMID- 24579261
TI  - "Infectious" infection control.

PMID- 24579262
TI  - Connect with policies and training.

PMID- 24579263
TI  - OSHA-required and CDC-recommended workplace training.

PMID- 24579264
TI  - The year that was: remarks from the immediate past president.

PMID- 24579265
TI  - In our society, communication is key.

PMID- 24579266
TI  - Oral health care for the pregnant patient.
AB  - Pregnancy is a unique time in a woman's life, accompanied by a variety of
      physiologic, anatomic and hormonal changes that can affect how oral health care
      is provided. However, these patients are not medically compromised and should not
      be denied dental treatment simply because they are pregnant. This article
      discusses the normal changes associated with pregnancy, general considerations in
      the care of pregnant patients, and possible dental complications of pregnancy and
      their management.

PMID- 24579267
TI  - Two suits dropped against Oklahoma surgeon, another filed.

PMID- 24579268
TI  - A review of intimate partner violence for case managers.
AB  - This article provides case managers with updated information on intimate partner
      violence. Case managers provide an important role in the identification,
      treatment, and prevention of intimate partner violence. Current federal laws
      provide direction and funding for a complex network of services for survivors.
      Effective identification involves screening and assessing risk of harm, severity
      of violence, and the survivor's readiness for change. Care planning involves
      working with the survivor and their families to build protective skills, make a
      safety plan, and build their life independent of violence.

PMID- 24579269
TI  - In the life: a case of autonomy, exploitation, and undue influence in geriatric
      home care.

PMID- 24579270
TI  - A pilot study examining the awareness, attitude, and burden of informal
      caregivers of patients with dementia.
AB  - Pakistan is 1 of 5 countries with the highest projected increase in prevalence of
      dementia in the Asia Pacific region (Access Economic, 2006), where there is a
      lack of structured support network for caregivers in general and for dementia
      caregivers in specific. The caregivers and other related individuals
      predominantly rely on traditional familial support for caregiving. This approach
      places immense burdens on the familial caregivers (Shaji, 2009). In Pakistan,
      there is paucity of research evidence on care of patients with dementia and the
      needs of caregivers dealing with such patients. This study explores awareness
      among caregivers, their attitudes toward family members suffering from dementia,
      and their experience of burden. In-depth interviews were conducted with 12
      caregivers of patients diagnosed with dementia in Rawalpindi/Islamabad Pakistan.
      There was a considerable lack of awareness about dementia as an illness among the
      caregivers. They reported a conflict between emotional and religious commitments
      to nurture older adult relatives and their experience of psychological, physical,
      and economic burden, resulting in occasional episodes of carelessness and
      violence toward them. The study indicated that women, particularly those who were
      employed outside of the home, reported higher levels of stress. It is suggested
      that support from extended family in all forms was perceived as a concrete form
      of stress relief by the primary caregiver. The findings of this study indicate
      that the social and financial burden of dementia on families of caregivers in
      Pakistan may be exacerbated if they do not have support. This indicates a need
      for multipronged intervention from both government and nongovernment
      organizations, as well as the community, to develop programs for caregivers that
      are nested within the cultural context of filial piety in Pakistan. These
      strategies should also be gender sensitive, giving priority to more at-risk
      groups.

PMID- 24579271
TI  - Factors associated with implementation of the POLST paradigm: results from a
      survey of Florida physicians.
AB  - OBJECTIVES: To investigate physicians' awareness and attitudes regarding the
      Physician Orders for Life-Sustaining Treatment (POLST) concept and to identify
      barriers and opportunities for its expansion. DESIGN: Cross-sectional
      questionnaire, using electronic survey instrument. SETTING: Community. PATIENTS:
      212 physicians from three Florida medical associations and the Florida State
      University College of Medicine clinical faculty responded to the survey. Of
      those, 67.9% were familiar with the concept of POLST. MEASUREMENTS AND MAIN
      RESULTS: Data were collected using a web-based survey, completed in June-July
      2012, consisting of qualitative and quantitative questions. Most (95.8%) agreed
      or strongly agreed that it was a physician's responsibility to discuss end-of
      life care and treatment options with patients. Satisfaction with current advanced
      directives was highly variable. However, a consensus about potential benefits of
      POLST exists, including assisting the discussion of end-of-life care, decreasing
      unwanted treatment, and lowering costs. More than 70% of respondents reported
      they would be more likely to use the POLST form if provided civil and criminal
      immunity; however, data analysis rendered the apparent association statistically
      insignificant. Qualitative data were also collected in the form of respondents'
      recommendations and additional comments. CONCLUSIONS: Physicians vary in their
      knowledge and opinions regarding the POLST paradigm. Broad opportunities may
      exist to improve physician knowledge and attitudes toward POLST. Dissemination of
      educational materials to physicians involved in the end-of-life planning process
      may increase physician support and use of POLST.

PMID- 24579272
TI  - Considerations in drafting Medicaid-compliant personal services contracts.

PMID- 24579273
TI  - How Jimmo will affect skilled nursing facility coverage.

PMID- 24579274
TI  - Clinical performance of fiber-reinforced nanofilled resin composite in
      extensively carious posterior teeth of children: 30-month evaluation.
AB  - OBJECTIVE: To evaluate the 30-month clinical performance of a nanofilled-resin
      composite with or without glass-fiber layering in restorations of large cavities
      in posterior teeth of children. STUDY DESIGN: A total of 71 restorations were
      placed in permanent molar teeth of 47 children (mean age 10.9 years) with (FRC;
      n=35) or without (RC; n=36) fiber layering. One operator placed all restorations.
      Restorations were evaluated according to the USPHS modified-Ryge criteria at
      baseline, 6, 12, 18, 24, and 30 months. The data were analyzed using Fisher 's
      exact and chi-square tests and outcomes were compared using the Cochran-Q test
      (p<0.05). RESULTS: The 30-month survival rates of the restorations were 97% and
      97.1% in the RC and FRC groups, respectively. Nanofilled-resin restorations with
      or without glass fiber-layering showed similarly high clinical performance. No
      differences were detected between the evaluated criteria when comparing baseline
      with any of the evaluation periods (p<0.05). After 30 months there were no
      secondary caries, change in anatomical form or postoperative sensitivity. Only
      minor changes for marginal adaptation, marginal discoloration, color match and
      surface texture were observed. CONCLUSION: It was concluded that nanofilled-resin
      composite applied with or without glass-fiber layering showed similar and good
      results in large cavities of posterior permanent teeth in children over a 30
      month period.

PMID- 24579276
TI  - KTP laser on microleakage of compomer restorations in Class V restorations.
AB  - AIM: To evaluate the effects of pulsed KTP (potassium-titanyl-phosphate) laser on
      decrease of dentinal microleakage of compomer restorations in primary teeth.
      METHOD: Twenty four primary molars were selected for the study After Class V
      cavity preparations in buccal and lingual surfaces, teeth were divided into three
      groups: Group 1: Control, Group 2: 1 WKTP laser Group 3: 1.5 WKTP laser. Then
      cavities were restored with compomer and teeth were thermocycled to 500 cycles,
      isolated and immersed in 0.5% basic fuchsin for 24 hours. Teeth were rinsed,
      dried, and sectioned, and microleakage was assessed by dye penetration at the
      occlusal and gingival surface of the teeth with stereomicroscope (40X). The data
      were analyzed with Kruskal-Wallis, Mann-Whitney U and Wilcoxon tests. RESULTS:
      When the scores of microleakage at the gingival margins of the groups were
      compared, the differences among the groups were found to be statistically
      significant (p<0.05). At the occlusal margins of the groups, there were no
      statistical differences (p>0.05). Comparing the gingival and the occlusal margins
      in the each group, statistically significant differences existed in the Groups 1
      and 3 (p<0.05). CONCLUSIONS: KTP laser is able to seal dentinal tubules and
      consequently reduce microleakage towards pulp in primary teeth.

PMID- 24579277
TI  - Molar luxations caused by holding water taps. Report of five cases.
AB  - Luxation of a primary molar occurs rarely. Here, we describe five cases of
      primary molar luxation caused by holding a water tap pipe in the mouth during
      bathing. The patients were aged 16 to 19 months and the mandibular first primary
      molar was affected in all five cases. The second primary molar had not erupted.
      It is assumed that the flange of the pipe got stuck in the interdental space
      between the mandibular primary canine and first primary molar and the affected
      first molar was pushed out by force with the flange acting as a lever.

PMID- 24579275
TI  - Effectiveness of a new fluoride varnish for caries prevention in pre-school
      children.
AB  - OBJECTIVE: To investigate the effectiveness of a new fluoride varnish (Clinpro
      White Varnish, 3MEspe, Seefeld, Germany) with regard to the caries incidence
      within a 2-year period STUDY DESIGN: A non-randomized sample of 400 children from
      the Kyffhauser district (Thuringia, Germany) was divided into a fluoride group
      (FG, biannual application of fluoride varnish) and control group (CG, no
      intervention). (Non-)cavitated caries lesions were recorded using World Health
      Organization (WHO) and Universal Visual Scoring System (UniViSS) criteria.
      Parents were given questionnaires to gather information about their socio
      economic status (SES). Non-parametric methods and binomial logistic regression
      were used for data analysis. RESULTS: There was a significant increase in caries
      incidence in both groups. The number of non-cavitated carious lesions was
      significantly lower in the FG (mean 2.2; sd 2.3) compared with the CG (mean 2.9;
      sd 1.9). Initial statistical analysis revealed that fluoride varnish might
      prevent non-cavitated carious lesions. When including SES as a confounder into
      regression model, potential preventive effect was lost. CONCLUSIONS: This study
      underlines the importance of the multi-factorial etiology of caries and
      illustrates that the effectiveness of biannual fluoride varnish application was
      evident in non-cavitated carious lesions only.

PMID- 24579278
TI  - Evaluation of three different caries removal techniques in children: a
      comparative clinical study.
AB  - AIM: To evaluate and compare the efficacy of chemo mechanical (carie care) caries
      removal method with rotary and hand excavation by assessing the amount of time
      taken, the pain response experienced by the children and the amount of residual
      caries left out. STUDY DESIGN: Twenty patients between the age groups of 5-7
      years were selected and caries removal was done by airotor hand instruments and
      cariecare gel. The efficacy, time taken and pain threshold was evaluated during
      caries removal. RESULTS: significant results were obtained when inter group
      comparison were made. CONCLUSION: it was concluded that cariecare was efficient
      in caries removal and can be used as an alternative for the airotor in management
      of dental caries especially in children.

PMID- 24579279
TI  - Pattern of parental acceptance of management techniques used in pediatric
      dentistry.
AB  - AIM: To evaluate parents' acceptance of management techniques in Israeli
      pediatric dental clinics. STUDY DESIGN: Ninety parents who accompanied their
      children to three pediatric dental clinics provided information on selected
      parameters including their attitudes about management techniques. RESULTS: 68.9%
      of the parents preferred to stay in the treatment room. The most accepted
      technique was positive reinforcement (81.1%) followed by tell-show-do (TSD)
      (76.7%, with younger parents more accepting than older, p = 0.049). The least
      accepted techniques were restraint (1.1%) and voice control (7.8%, especially by
      parents with the highest dental anxiety, p = 0.002). Sedation was unacceptable by
      15.6% of the parents: those with the lowest dental anxiety agreed to sedation
      significantly more than those with greater dental anxiety (p = 0.031).
      CONCLUSIONS: Parents preferred more positive approaches and management techniques
      that involve demonstrations geared for the child's level of understanding.
      Restraint and voice control were more strongly rejected than sedation.

PMID- 24579281
TI  - Knowledge and practice of eating disorders among a group of adolescent dental
      patients.
AB  - OBJECTIVES: The objectives are to ascertain how much is known about the eating
      disorders of bulimia and anorexia nervosa in a group of female adolescents, to
      determine if they had practiced behaviors consistent with these eating disorders,
      and to determine if there was a disconnect with actual and perceived healthy
      weight status. STUDY DESIGN: 126 research subjects completed a survey instrument.
      Embedded in the eighteen question survey were the five "SCOFF" questions, to
      determine if an eating disorder may exist. The BMI percentile was obtained for
      all participants. RESULTS: 18.3% of the research sample may have an eating
      disorder as predicted by the SCOFF questions. Of those with a suspected eating
      disorder, only 38% could correctly identify the best description of bulimia
      nervosa and 50% for anorexia nervosa. The BMI percentiles were higher in the
      group suspected of having an eating disorder CONCLUSIONS: Young adolescent
      females are at risk for eating disorders. Educational interventions should be
      directed at this young age group. If the at-risk individuals knew more about the
      consequences of these disorders, they may be less likely to practice the
      behaviors.

PMID- 24579280
TI  - Preschool children's taste acceptance of highly concentrated fluoride compounds:
      effects on nonverbal behavior.
AB  - OBJECTIVE: The aim of this video-based study was to examine the taste acceptance
      of children between the ages of 2 and 5 years regarding highly concentrated
      fluoride preparations in kindergarten-based preventive programs. STUDY DESIGN:
      The fluoride preparation Duraphat was applied to 16 children, Elmex fluid to 15
      children, and Fluoridin N5 to 14 children. The procedure was conducted according
      to a standardized protocol and videotaped Three raters evaluated the children's
      nonverbal behavior as a measure of taste acceptance on the Frankl Behavior Rating
      Scale. The interrater reliability (intraclass correlation coefficient; ICC) was
      .86. In an interview, children indicated the taste of the fluoride preparations
      on a three-point "smiley" rating scale. The interviewer used a hand puppet during
      the survey to establish confidence between the children and examiners. RESULTS:
      Children's nonverbal behavior was significantly more positive after Fluoridin N5
      and Duraphat were applied compared to the application of Elmex fluid. The same
      trend was found during the smiley assessment. The response of children who
      displayed cooperative positive behavior before the application of fluoride
      preparations was significantly more positive than those who displayed
      uncooperative negative behavior. CONCLUSION: To achieve a high acceptance of the
      application of fluoride preparations among preschool children, flavorful
      preparations should be used.

PMID- 24579282
TI  - A novel distraction technique for pain management during local anesthesia
      administration in pediatric patients.
AB  - AIM: The aim of this study was to assess the effect of an active and novel
      distraction technique WITAUL (Writing In The Air Using Leg) on the pain behavior
      observed and reported by children receiving local anesthesia injections prior to
      dental treatment. STUDY DESIGN: The study was conducted on 160 children (80 in
      control and 80 in intervention group) between the ages of 4- 10 years. During the
      administration of anesthesia the children in the control group were made to relax
      by means of deep breathing and those in the intervention group were taught to use
      the WITAUL distraction technique. the behavior of the children aged 4- 5 years
      was noted using the Modified Toddler- Preschooler Post operative Pain Scale
      (TPPPS) and that of children aged above 6 years was measured using the FACES Pain
      Scale-Revised (FPS-R). RESULTS: The use of WITAUL was found to be statistically
      significant (p value < 0.0001) compared to the control method in serving as a
      distraction and hence in managing pain during local anesthesia administration.
      The mean Modified TPPPS scores (4- 5 year olds) for the WITAL group was 2.46 +/-
      1.752 and that of the control was 5.64 +/- 2.328. The mean FPS-R scores (6 - 10
      year olds) for the WITAUL group was 3 +/- 1.748 and that of the control group was
      6.26 +/- 1.858. CONCLUSION: The WITAUL technique therefore appears to be a simple
      and effective method of distraction during local anesthesia administration in
      pediatric patients.

PMID- 24579284
TI  - Effectiveness of CRT at measuring the salivary level of bacteria in caries prone
      children with probiotic therapy.
AB  - AIM: This IRB approved clinical trial was to determine the effect of "over the
      counter" probiotic supplements on the Caries Risk Test- CRT- (Ivoclar) results of
      the oral microflora in high caries risk children. STUDY DESIGN: Sixty subjects 6
      to 12 years old with a caries risk assessment (CAMBRA) of moderate to high
      (caries prone) were evaluated by an analysis of the difference in the salivary
      levels of pathogenic bacteria (mutans streptococci and Lactobacilli). The
      subjects were randomly selected by randomizing software and assigned to two
      diferent Groups. Group A used PerioBalance (Lactobacilli reuteri-CFU of 200
      million) lozenges for 28 days. Group B used the EvoraKids (Streptococcus uberis
      KJ2, Streptococcus oralis KJ3, Streptococcus rattus JH1 45, > or = 100 million)
      probiotics chewable tablets for 30 days. Salivary samples were collected then
      incubated for 48 hours for colony counting and ranking. Follow up testing with
      the CRT was performed after 60 days at a follow up visit. RESULTS: There was a
      statistically significant diference in the CRT results between the pre and post
      use of the probiotics. PerioBalance; SM results t= -6. 78, p< .0001, Lactobacilli
      results t= -5.762, p< .0001, EvoraKids SMresults t= -7.33, p< .0001, Lactobacilli
      results t= -2.952, p= .0068. CONCLUSIONS: The CRT values obtained with caries
      prone children may be significantly affected by probiotic use. Based on this
      study's results the following conclusions can be made: Both EvoraKids and
      PerioBalance affected the CRT results by significantly decreasing the number of
      S. mutans and lactobacilli present in the salivary samples.

PMID- 24579283
TI  - Effect of proanthocyanidin treatment on the bonding effectiveness of adhesive
      restorations in pulp chamber.
AB  - OBJECTIVE: To analyze the effect of proanthocyanidin (PA) treatment of the pulp
      chamber dentin after NaOCl and EDTA irrigation on the microleakage and
      interfacial morphology of adhesive restorations. STUDY DESIGN: Pulp chambers of
      66 extracted permanent molars were exposed. In half of the samples, pulp chamber
      dentin was bonded with Clearfil S3 after irrigation with normal saline (Group1a);
      1% NaOCl and 17% EDTA (Group1b) or 1% NaOCl, 17% EDTA and 30% PA (Group1c) and in
      other half samples, pulp chamber dentin was bonded with Futurabond NR after
      irrigation with normal saline (Group 2a); 1% NaOCl and 17% EDTA (Group 2b) or 1%
      NaOCl, 17% EDTA and 30% PA (Group 2c). After adhesive procedures, Filtek Z 250
      restorations were placed in the pulp chambers. Microleakage assessment was done
      in ten samples from each group and scanning electron microscopic examination was
      done in one sample from each group. Statistical analysis was done using Mann
      Whitney and Kruskal Wallis tests at a significance level of P<0.05. RESULTS: Both
      the adhesives showed extensive microleakage. NaOCl and EDTA irrigation had no
      significant effect on the microleakage of both the adhesives. PA treatment of the
      pulp chamber dentin after NaOCl and EDTA irrigation significantly reduced
      microleakage in both the adhesives. CONCLUSION: It was concluded that 1 minute
      application of 30% proanthocyanidin solution in the pulp chamber after NaOCl and
      EDTA irrigation improved the subsequent bonding of self-etch adhesives to pulp
      chamber dentin.

PMID- 24579285
TI  - Emotional intelligence subscales: are they correlated with child anxiety and
      behavior in the dental setting?
AB  - OBJECTIVES: The present study aimed at evaluating the correlation between
      emotional intelligence subscales and childs anxiety and behavior in the dental
      setting. STUDY DESIGN: The study included 123 children aged 7-12 years, who were
      scheduled to attend two consecutive sessions. In the first session, the Bar-On
      Emotional Quotient Inventory: Youth Version (Bar-on EQ-I: YV) was administered to
      participants. The anxiety and behavior in children was evaluated during similar
      dental procedures in the second session using the Clinical Anxiety Rating Scale
      and the Frankl scale, respectively. RESULTS: 23 children were eliminated from the
      study, leaving 100 participants (47 boys and 53 girls) with a mean age of 9.32 +/
      1.59 years for study. There were statistically significant positive correlations
      between Frankl score and EQ total score (p < 0.001), interpersonal scale (p <
      0.001), intrapersonal scale (p < 0.001), stress management (p = 0.03) and
      adaptability scale (p < 0.001). Significant negative correlations were found
      between anxiety score and, EQ total score (p < 0.001), interpersonal scale (p <
      0.001), intrapersonal scale (p < 0.001), and adaptability scale (p < 0.001).
      Anxiety and stress management were not correlated (p = 0.16). Total EQ and EQ
      subscales can predict significance variance of Frankl score (p < 0.05) and
      anxiety score (p < 0.05) without confounding effect of age and sex (p > 0.05).
      CONCLUSIONS: The results provide evidence that children with higher total EQ as
      well as higher scores of intrapersonal, interpersonal, adaptability and stress
      management scales can generally be flexible and effective in coping in the dental
      setting. Higher score in stress management subscale seems to be related to better
      control over affective information including anxiety compared with other
      subscales in stressful situations. Overall, they behave and cooperate better than
      children with lower scores.

PMID- 24579286
TI  - A randomized trial on the inhibitory effect of chewing gum containing tea
      polyphenol on caries.
AB  - OBJECTIVE: The purpose of the study was to determine the cariostatic potential of
      a chewing gum containing tea polyphenol. STUDY DESIGN: A total of 157
      schoolchildren aged 8-9 years were randomly allocated into three groups. Two
      groups received chewing gum with or without tea polyphenol. A third group did not
      receive any chewing gum. A single examiner assessed the caries status for all
      participates at baseline, 12 months and 24 months. A one-way analysis of variance
      (ANOVA) was performed to evaluate differences among the groups at each interval
      The Chi-square test was used to compare the caries-free rate among the three
      groups. RESULTS: The mean DMFT increment was 0.17 for the polyphenol gum group,
      0.60 for the control gum group, and 1.15 for the no gum group. Children who
      chewed gum containing tea polyphenol had a significantly lower mean DMFS
      increment over the 24-month period than did the other two groups (p < 0.05). The
      caries-free rate in the polyphenol gum group was significantly higher than that
      in the other two groups (p < 0.05) after two years. CONCLUSION: These findings
      indicated that the oral application of chewing gum with tea polyphenol has an
      inhibitory effect on dental caries.

PMID- 24579287
TI  - Lead exposure and its relation to dental caries in children.
AB  - Environmental pollution is a significant health hazard and is mainly caused by
      commercialization. The etiology of dental caries is multifactorial and one such
      factor is exposure to trace element such as lead. AIM: Hence, the present study
      was carried out to find out the correlation between the levels of lead in the
      enamel, saliva and dental caries in children. METHOD: 90 children aged 5 years
      consisting of both genders from different kindergartens along Coastal Karnataka
      were included in the study. The selected children were divided into 3 groups as;
      control group, early childhood caries (ECC) group and severe-ECC (S-ECC) group
      respectively. Enamel and salivary lead level was assessed by using graphite
      atomic absorption spectrophotometry. RESULTS: Mean enamel lead levels in the
      control, ECC and S-ECC group were 47.7, 85.45 and 90.43 ppm respectively and mean
      salivary lead levels were 0.23, 1.7 and 1.77 ppm respectively which was
      statistically very highly significant (p < 0.001) with no gender predilection.
      There was a positive correlation seen between the enamel and the salivary lead
      levels (p > 0.05). CONCLUSION: The enamel and the saliva of all the children had
      measurable amounts of lead and its levels increased with increase in severity of
      dental caries proving the cariogenic potential of lead. A positive correlation
      was seen between the enamel and the salivary lead levels.

PMID- 24579288
TI  - Oral tissue irritants in toothpaste: a case report.
AB  - In this case, an adolescent patient presented with multiple, asymptomatic
      ulcerated lesions- resembling aphthous ulcerations- located in the oral cavity.
      The etiology of these lesions appeared to be associated with soft tissue
      irritants found in the patient's toothpaste. This report highlights the need to
      rule out known oral irritants in dentifrices for patients who present with oral
      ulcerations.

PMID- 24579289
TI  - Initial experience with dexmedetomidine for dental sedation in children.
AB  - Sedation of uncooperative children for dental treatment is difficult since
      treatment is mainly carried out inside the oral cavity. Dexmedetomidine (DEX),
      recently introduced into clinical practice, has little influence on respiratory
      system even at high doses. We present cases of patients who underwent dental
      treatment under sedation using DEX infusion. DEX at a dose of 1 microg/kg was
      administered over 10 min after intravenous cannulation. DEX was infused to
      maintain sedation level within the range of the Observer's Assessment of
      Alertness and Sedation (OAA/S) scale 3- 4 throughout dental treatments. They were
      successfully treated under DEX sedation without any complications. Their
      uncooperative behaviors were successfully managed under DEX sedation.

PMID- 24579290
TI  - Prevalence of dental caries and its impact on quality of life (QoL) among HIV
      infected children in Kenya.
AB  - AIM: To determine the prevalence of dental caries and its impact on QoL among HIV
      infected children in Kenya. STUDY DESIGN: Cross-sectional survey of HIV-positive
      children aged 3-15 years. METHOD: Two hundred and twenty participants were
      selected by consecutive sampling. Dental examination was undertaken to determine
      the presence of dental caries among the children using the dmft/DMFT indices. The
      children's perceived QoL in the domains of oral symptoms, functional limitations,
      emotional and social wellbeing was assessed using the WHO Simplified Oral Health
      Questionnaires for children. RESULTS: The overall prevalence of dental caries was
      65% whence the prevalence in the deciduous dentition was 50% while that of the
      permanent dentition was 30.9%. The mean dmft and DMFTscores were 1.75 and 1.08
      respectively. Children with high dmft manifested negative impacts on appearance,
      chewing, biting hard foods and missing school on account of toothache and
      discomfort, while in the permanent dentition children with high DMFT had a
      negative impact on biting hard foods. CONCLUSION: A high caries experience had
      significant negative impacts on the children's QoL, especially in the primary
      dentition.

PMID- 24579291
TI  - Alternative approaches to managing the cleft alveolus.
AB  - The cleft alveolus component of the oral cleft deformity is addressed with a
      separate surgical stage. Several host and operator related factors affect the
      surgical outcome. When factors that increase the likelihood of secondary alveolar
      bone graft failure are identified, alterative methods like dentoalveolar
      distraction (DAD) may be employed. In infants, molding of the alveolar segments
      is possible and when a synergistic surgical approach is used, the possibility of
      successful alveolar cleft repair is increased. The authors present two case
      reports wherein the use of nasoalveolar molding (NAM) and DAD helped to tackle
      the alveolar cleft deformity.

PMID- 24579292
TI  - Two milestones for the International Journal of Pharmaceutical Compounding.

PMID- 24579293
TI  - Disguising the taste of antiretrovirals for pediatric patients infected with
      Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome: creative flavor
      compounding and techniques, part 2.
AB  - Adherence to antiretrovirals for pediatric patients is challenging for a variety
      of reasons, many of which are quite obvious. The medication's taste and texture
      may contribute to a child's resistance to following their regimen. To make the
      problem of compliance even more complex, there are fewer pediatric-friendly
      formulations available and fewer alternative options for antiretrovirals when
      compared to formulations and alternatives available to adults. For the sake of
      compliance, it is vital that parents and/or caregivers be offered innovative ways
      to disguise the taste of antiretrovirals for pediatric patients infected with
      Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome. Compounding
      pharmacists can play an important role in finding answers to this situation. This
      article provides an in-depth discussion on some of the specific flavoring and
      taste-masking options that are available in the effort to increase adherence in
      the pediatric patient population.

PMID- 24579294
TI  - Clinical utility of pharmacogenetic testing in compounding pharmacy.
AB  - Pharmacists must consider all factors when dosing medication for a patient. Until
      recently, however, one key piece to this puzzle was missing--genetics. This
      invisible piece of the puzzle can now be utilized with pharmacogenetic testing.
      By using pharmacogenetic testing, the compounding pharmacist will be able to
      better predict disease risk as well as the pharmacodynamic and pharmacokinetic
      actions of the prescriptions their patients are taking. Pharmacogenetics is
      poised to become the standard of care that not only physicians are embracing, but
      pharmacists can utilize to better personalize their patient's needs.

PMID- 24579295
TI  - Considerations for pharmacists working in major disaster areas.
AB  - Japan experienced the Great East Japan Earthquake on March 11, 2011. Medical
      workers, including pharmacists, responded to the stricken areas to assist the
      affected patients with their medical needs. Although there are many published
      reports concerning the human suffering and medical problems resulting from this
      earthquake, very few of the published reports are by pharmacists documenting
      their experiences and perspective. It is important that pharmacists who respond
      to disasters document and report their experiences, as this information is vital
      for future responders. The authors, who were also responders of the Great East
      Japan Earthquake, evaluated the wasted drugs, compared the wasted drugs with the
      number of drugs prepared before dispatch to the affected areas, and documented
      the information that was gathered. A list of drugs, which was necessary to handle
      the subacute and chronic phases used at the stricken areas, was prepared and drug
      requirement tendencies investigated. The information gathered in this report may
      help pharmacists who are involved in similar situations in the future.

PMID- 24579297
TI  - Physicians, pharmacists, and the importance of quality pharmacy compounding.
AB  - The adverse events associated with the New England Compounding Center are rare.
      Nonetheless, when they do occur, such events tend to gain a lot of press
      coverage, and the news stories are repeated over and over for months, resulting
      in an unfavorable impression of the profession of pharmaceutical compounding. It
      is evident and appropriate that pharmacy practice, including compounding
      pharmacy, is well-regulated and monitored. The fact is that compounded
      medications are a necessity for reasons such as commercial products not being
      patient-specific, the unavailability of limited dosage forms and strengths from
      manufacturers, drug shortages, and the unavailability of manufactured drugs for
      pediatrics, along with many other reasons outlined within this article.

PMID- 24579298
TI  - HR 3204--The Drug Quality and Security Act: what does it say? What does it mean?
      What happens now?

PMID- 24579296
TI  - Improving the review of standard operating procedures: a novel electronic system
      for compounding pharmacies.
AB  - Since the New England Compounding Center disaster in 2012, the importance of
      following correct procedures during every phase of customized pharmacy has been a
      focus of governmental interest and action as well as public scrutiny. Many
      pharmacies rely on the rote review of standard operating procedures to ensure
      that staff members understand and follow protocols that ensure the safety and
      potency of all compounds prepared, but that approach to continuing education can
      be cumbersome and needlessly time-consuming. In addition, documenting and
      retrieving evidence of employee competence can be difficult. In this article, we
      describe our use of online technology to improve our methods of educating staff
      about the full range of standard operating procedures that must be followed in
      our pharmacy. The system we devised and implemented has proven to be effective,
      easy to update and maintain, very inexpensive, and user friendly. Its use has
      reduced the time previously required for a read-over review of standard operating
      procedures from 30 or 40 minutes to 5 or 10 minutes in weekly staff meetings, and
      we can now easily document and access proof of employees' comprehension of that
      content. It is our hope that other small compounding pharmacies will also find
      this system of online standard operating procedure review helpful.

PMID- 24579299
TI  - A growing codependency: compounding pharmacy and safety.
AB  - Pharmacists and pharmacy technicians are in constant contact with potent
      compounds. When compounding with powders, there is a susceptibility to
      environmental conditions such that proper containment be in place to keep the
      employees safe, the medicine free from cross contamination or the introduction of
      outside contaminants, and the workplace free from floating active pharmaceutical
      ingredient particles. Adapting powder hoods as safety devices that work in direct
      relation to clearly defined standard operating procedures and good lab practices
      will facilitate a safer lab environment for employees and ensure good-quality
      prescriptions. This article discusses the safety concerns of compounding with
      powders and the safety measures to consider when purchasing powder hoods.

PMID- 24579300
TI  - Basics of compounding with balsams.
AB  - Balsams have been used in pharmacy for centuries for many different purposes.
      Balsams include benzoin, Peruvian balsam, storax, and tolu balsam. Balsams are
      aromatic and usually oily resinous substances flowing from various plants and
      generally containing some amount of benzoic or cinnamic acid. Historically, they
      have been used orally and topically in various formulations. Today, their primary
      use is topically in solutions, ointments, creams, and lotions. Today, the most
      common use would be in diaper ointments and to treat various skin disorders.
      Pharmacists are still called upon to compound various preparations using balsams.

PMID- 24579301
TI  - Stability of non-aqueous topical tetracaine and clotrimazole solutions in
      polypropylene droptainer bottles.
AB  - Tetracaine topical solution may improve patient adherence with topical
      clotrimazole therapy for fungal otitis externa. The chemical stability of
      tetracaine 1% and combination clotrimazole 1% with tetracaine 1% topical
      solutions was determined using a stability-indicating high-performance liquid
      chromatography assay. Propylene glycol and polyethylene glycol 400 were used as
      anhydrous solvents. Standard curves for tetracaine and clotrimazole were linear
      with r2 > or = 0.999. Clotrimazole did not degrade in either propylene glycol or
      polyethylene glycol 400 throughout the 90-day study period. Tetracaine degraded
      significantly in propylene glycol but not in polyethylene glycol 400. A beyond
      use date of 90 days is supported for tetracaine and the combination clotrimazole
      tetracaine solution in polyethylene glycol 400. A beyond-use date of 60 days is
      supported for tetracaine and the combination clotrimazole-tetracaine in propylene
      glycol.

PMID- 24579302
TI  - Comparing suppository mold variability which can lead to dosage errors for
      suppositories prepared with the same or different molds.
AB  - Suppository molds must be properly calibrated to ensure accurate dosing. There
      are often slight differences between molds and even in the cavities within a
      mold. A method is presented for the calibration of standard aluminum 6-, 12-, 50
      , or 100-well suppository molds. Ten different molds were tested using water for
      volume calibration, and cocoa butter for standardization involving establishing
      the density factor. This method is shown to be straightforward and appropriate
      for calibrating suppository molds.

PMID- 24579303
TI  - Stability of nitroglycerin 110 mcg/mL stored in polypropylene syringes.
AB  - Various angiography procedures at Mayo Clinic (Rochester campus) require small
      bolus doses of injectable nitroglycerin. Commercially acquired containers of
      injectable nitroglycerin provide excessive amounts of drug for these procedural
      needs, so syringes were chosen as a container for dispensing of the dose needed.
      Due to nitroglycerin's known chemical attributes of volatility and sorption to
      plastic surfaces, careful consideration of the stability needs to be taken into
      account when storing in a syringe. Since there is a lack of stability information
      in the literature, we studied the stability of nitroglycerin in polypropylene
      syringes over 90 days. Methods used for this study consisted of a validated
      stability-indicating high-performance liquid chromatographic assay, visual
      appearance, and pH. Samples were stored protected from light at ambient
      controlled temperature and consisted of nitroglycerin 110 mcg/mL in 5% dextrose
      injection 10.1 mL in 12 mL Terumo polypropylene syringes. Samples were tested at
      intervals up to 90 days. Results from the visual portion of the study showed
      clear, colorless, and particulate-free solutions throughout the 90-day study
      period. The pH results started at 4.27 +/- 0.13 (day 0) and ranged from 4.19 +/-
      0.17 to 4.92 +/- 0.43 throughout the study period. Potency test results revealed
      a day 0 concentration of 104.242 +/- 0.193 mcg/mL (batch 1) and 122.483 +/- 0.168
      mcg/mL (batch 2). Results trended downward with percentage of day 0 concentration
      of 92.2% +/- 2.4% at day 14 and of 81.4% +/- 4.9% at day 90. Chromatographic
      profiles of the samples exhibited insignificant changes over the study period.
      The nitroglycerin peak was spectrally pure based on peak-purity analysis,
      suggesting that sorption to the polypropylene syringe is one possible reason for
      the concentration decline over time, but nitroglycerin is a volatile compound and
      loss through vaporization cannot be ruled out. Nitroglycerin 110 mcg/mL in 5%
      dextrose injection, packaged in Terumo polypropylene syringes with 10.1 mL
      aliquots, maintained 90% of syringe potency for 24 days when stored protected
      from light under controlled ambient conditions.

PMID- 24579305
TI  - Augmented reality for readers and authors.

PMID- 24579304
TI  - Ex vivo percutaneous absorption of ketamine, bupivacaine, diclofenac, gabapentin,
      orphenadrine, and pentoxifylline: comparison of versatile cream vs. reference
      cream.
AB  - This ex vivo human percutaneous absorption study evaluated a set of six model
      drugs (ketamine hydrochloride, bupivacaine hydrochloride, diclofenac sodium,
      gabapentin, orphenadrine citrate, pentoxifylline) from two popular formulations
      for topically applied compounding preparations. The compounded preparations used
      in this study were Versatile cream and a reference cream. Each formulation was
      applied to human trunk skin mounted on Franz Diffusion Cells, 50 mg/chamber (or
      28.2 mg/cm2). Serial dermal receiver solutions were collected for 48 hours.
      Analysis of the resultant data supports the concept that the Versatile base
      formulation provides improved characteristics relative to the reference base.
      This is of key importance where the patient does not show clinical improvement
      when a conventional topical delivery vehicle is used in the formulation. From the
      results, it is reasonable to anticipate that, relative to the reference
      formulation, the Versatile formulation provides enhanced transdermal delivery of
      some analgesic medications.

PMID- 24579306
TI  - [Research progress in heritable dyslipidemia].
AB  - Dyslipidemia is defined as high levels of serum cholesterol and/or triglycerides.
      Dyslipidemia often leads to severe cardiovascular diseases including coronary
      heart disease and stroke as the first clinical manifestation, thus threatening
      the health of human beings. Dyslipidemia diseases can be caused by the genetic
      factors, including the Mandelian or polygenic inheritance. Traditional methods of
      identifying genes associated with dyslipidemia are mainly DNA sequencing and
      linkage analysis, suitable for Mendelian genetic dyslipidemia disease. The rise
      of next-generation sequencing technology applies to not only Mandelian
      inheritance, but also complex forms of dyslipidemia diseases. Since 2006, genome
      wide association studies (GWAS) screened out many causative genes associated with
      dyslipidemia, and most of these genes were the previously identified ones by the
      pedigree-based classic approaches. Furthermore, GWAS revealed that there were the
      different frequencies of gene variations related to complex forms of dyslipidemia
      diseases. Most of the identified single nucleotide polymorphisms (SNPs)
      associated with dyslipidemia are located in non-coding regions and thus people
      gradually focus on the gene variations of these loci. The identification of the
      causative genes will provide new insights into the pathophysiology of
      dyslipidemia diseases and a step toward therapeutic intervention. This review
      summarized recent pro-gress in heritable dyslipidemia.

PMID- 24579307
TI  - [The function and application of the IL28B gene in HCV infection and treatment].
AB  - Hepatitis C virus (HCV) is the etiological factor for Hepatitis C, which is one
      of the most important pathogenic factors of chronic liver diseases, cirrhosis and
      even hepatocellular carcinoma. HCV infection brings great threat to human health.
      Host genetic background could impact HCV infection, viral clearance, and
      treatment. Recently, some genome-wide association studies (GWAS) of HCV patients
      were performed. The results showed that single nucleotide polymorphisms (SNPs) of
      the IL28B gene, which encodes protein IFN-lambda3, are associated with viral
      clearance and treatment effectiveness of HCV patients who were cured by PEG
      IFNalpha combined with ribavirin (RBV). IFN-lambda3 interacts with its acceptor,
      a heterodimer (IFN-lambdaR1 x IL-10R2), and upregulates the IFN-stimulated gene
      factors (ISGF). IFN-lambda3 plays roles in antiviral, antitumor, and
      immunoloregulation, and thus it might become a potential drug for Hepatitis C
      treatment. However, the mechanism of the IL28B gene in HCV infection and
      treatment is unclear, and further studies are needed to reveal the veils and
      provide theoretical basis for developing a new antiviral drug in clinic.

PMID- 24579308
TI  - [Characterization and identification of functional elements in non-coding DNA
      sequences].
AB  - The non-coding DNA sequences refer to non-protein-coding DNA sequences in genome.
      These sequences can bind with transcription factors or be transcribed as
      functional RNAs, thus participating in the regulation of many physiological
      activities and pathological processes. Aiming at gene expression regulation, this
      review focuses on the recent progress of non-coding DNA and illustrates their
      structures, functions and potential acting mechanisms. Meanwhile, some
      computational and experimental methods of identifying functional elements in the
      non-coding DNAs are introduced. Finally, further studies in this field are
      proposed.

PMID- 24579310
TI  - [Recent advances in the techniques of protein-protein interaction study].
AB  - Protein-protein interactions play key roles in the development of organisms and
      the response to biotic and abiotic stresses. Several wet-lab methods have been
      developed to study this challenging area,including yeast two-hybrid system,
      tandem affinity purification, Co-immunoprecipitation, GST Pull-down, bimolecular
      fluorescence complementation, fluorescence resonance energy transfer and surface
      plasmon resonance analysis. In this review, we discuss theoretical principles and
      relative advantages and disvantages of these techniques,with an emphasis on
      recent advances to compensate for limitations.

PMID- 24579309
TI  - [CRISPR/Cas: a novel way of RNA-guided genome editing].
AB  - Bacteria and archaea have evolved an adaptive immune system, known as type II
      prokaryotic clustered regularly interspaced short palindromic repeats
      (CRISPR)/CRISPR-associated (Cas) system, which uses short RNA to direct the
      degradation of target sequences present in invading viral and plasmid DNAs.
      Recent advances in CRISPR/Cas system provide an improved method for genome
      editing, showing robust and specific RNA-guided endonuclease activity at targeted
      endogenous genomic loci. It is the latest technology to modify genome DNA
      specifically and effectively following zinc finger nucleases (ZFNs) and TALE
      nucleases (TALENs). Compared with ZFNs and TALENs, CRISPR/Cas is much simpler and
      easier to engineer. This review summarizes recent progress, and discusses the
      prospects of CRISPR/Cas system, with an emphasis on its structure, principle,
      applications and potential challenges.

PMID- 24579311
TI  - [Regulation of differentiation of mesenchymal stem cells by the Hippo pathway
      effectors TAZ/YAP].
AB  - Mesenchymal stem cells (MSCs) are pluripotent cells which can differentiate into
      several distinct lineages, such as chondrocytes, adipocytes and myofibers. It has
      been reported that the lineage-specific transcriptional factors including Runt
      related transcription factor 2 (RUNX2), Peroxisome proliferator-activator
      receptor gamma (PPARgamma) and Myogenic differentiation 1 (MyoD) may play key
      regulatory roles among the differentiation of MSCs. Recently, researches have
      confirmed that the Hippo pathway impacts the differentiation fates of MSCs
      through regulating the activity of line- age-specific transcription factors by
      the Hippo pathway effectors Tafazzin (TAZ) and/or Yes-associated protein (YAP).
      The interaction between TAZ and RUNX2 boosts the osteogenic processes and
      promotes MSCs differentiating into osteoblast lineage. However, PPARgamma binding
      to TAZ may inhibit the adipocytes differentiation, and thus overexpression of TAZ
      in mesenchymal stem cell-like cells increases the expression of myogenic genes
      and hastens myofiber formation through a MyoD-dependent manner. Moreover, other
      signaling pathways (such as BMP-2, TNF-alpha, Eph-Ephrin, etc.), small molecules
      (KR62980, TM-25659, etc.), and mechanistic stimuli can also affect the fate by
      regulating the activity of TAZ/YAP. In this review, we summarized the signaling
      pattern of Hippo pathway and the function mechanism of TAZ and/or YAP by
      enumerating their interaction to several lineage-specific transcriptional factors
      and relationship with other signal pathways during MSCs differentiation.

PMID- 24579312
TI  - [Genome-wide association study of high-altitude pulmonary edema in Han Chinese].
AB  - High-altitude pulmonary edema (HAPE) is a non-cardiogenic pulmonary edema that is
      always found among unacclimatized persons after rapid ascent to high altitude,
      and HAPE is caused by the interaction of genetic and environmental factors. To
      screen and analyze the susceptibility genes and single nucleotide polymorphisms
      (SNPs) of HAPE in Han Chinese, the DNA samples of 40 patients with HAPE and 33
      healthy controls, who performed the reconstruction tasks from the plain region in
      Yushu area of Qinghai province during May of 2010 to July of 2012, were scanned
      by Affymetrix SNP Array 6.0 Chips in this study. Genome-wide association study
      (GWAS, by PLINK software) was used to screen the susceptibility genes and genetic
      markers, and a total of 57 SNPs were found to be significantly different between
      case and control groups (adjust P < 0.05). GO and Pathway enrichment analysis of
      74 genes around the 57 SNPs indicated that these genes were significantly
      correlated with prostanoid metabolic process, arachidonic acid metabolism and
      nitrogen metabolism (adjust P < 0.05), which were involved in the
      physiopathologic mechanism of HAPE. Our studies suggest that these genetic
      polymorphisms and genes were associated with HAPE.

PMID- 24579314
TI  - [Molecular evolution of the poplar MIR169 gene family].
AB  - MicroRNAs (miRNAs) are a class of short non-coding RNAs found widely in
      eukaryotic organisms. The ptc-MIR169 gene family, which consists of 33 members,
      is the largest miRNA gene family in poplar (Populus trichocarpa) It is
      significant to analyze the evolution of the ptc-MIR169 gene family in order to
      understand the evolutionary mechanisms of miRNAs in poplar. In the present study,
      we investigated the molecular phylogeny, duplication, expression and target genes
      of the MIR169 gene family in poplar. Both tandem duplications and chromosome
      segmental duplications contributed to the expanding of ptc-MIR169 gene family,
      and the expression patterns diversified obviously among the gene family. These
      findings suggest that the ptc-MIR169 gene family is involved in complex
      regulatory networks, and plays significant roles in development and stress
      response in poplar. This paper provides a reference for the evolutionary study of
      miRNAs in poplar and related species in Salicaceae.

PMID- 24579315
TI  - [Molecular evolution of the sulphite efflux gene SSU1 in Saccharomyces
      cerevisiae].
AB  - The SSU1 gene encoding a membrane sulfite pump is a main facilitator invovled in
      sulfite efflux. In Saccharomyce cerevisiae, various range of resistance to
      sulfite was observed among strains. To explore the evolution traits of SSU1 gene,
      the population data of S. cerevisiae were collected and analyzed. The
      phylogenetic analysis indicated that S. cerevisiae population can be classified
      into three sub-populations, and the positive selection was detected in population
      by McDonald-Kreitman test. The anaylsis of Ka/Ks ratios further showed that S.
      cerevisiae sub-population was undergoing positive selection. This finding was
      also supported by PAML branch model. Nine potential positive selection sites were
      predicted by branch-site model, and four sites exclusively belong to the sub
      population under positive seletion. The data from ssulp protein structure
      demonstrated that three sites are substitutions between polar and hydrophobic
      amino acids, and only one site of substitutaion from basic amino acid to basic
      amino acid (345R/K). Because amino acid pKa values are crucial for sulfite pump
      to maintain their routine function, positive selection of these amino acid
      substitutions might affect sulfite efflux efficient.

PMID- 24579313
TI  - [Analysis of SCA3/MJD3 gene mutation and genetic polymorphism in a guangxi family
      with spinocerebellar ataxia 3].
AB  - Autosomal dominant cerebellar ataxias (ADCAs) comprise a group of genetically
      heterogeneous neurodegenerative disorders among which spinocerebellar ataxia type
      3 (SCA3) represents the most common form of SCAs worldwide. The fragments of
      SCA3/MJD gene,which is the member of family GXPL1,were amplified by polymerase
      chain reaction (PCR). The PCR products of SCA3/MJD gene were detected with
      capillary electrophoresis (CE) and sequencing to evaluate the size of CAG
      repeats, feature in the transmission and the mutation in the family with SCA3 in
      Guangxi province. The results showed that the exon 10 of the SCA3/MJD gene
      contains 64-71 CAG repeats in all of the affected individuals and three
      asymptomatic carriers of the family. The number of the CAG repeats during
      transmission in the normal individuals carrying CGG allele remains consistent,
      suggesting that CGG allele could have no effect on intergenerational stability of
      CAG repeats in normal individuals. In addition, two novel point mutations were
      identified: IVS9-113 T > C in the intronic region and a missense mutation 220 G >
      A (Glu > Gly) in the encoding region. These two novel point mutations have not
      been reported and the effect of the mutations on the phenotype of SCA3 is not
      clear.

PMID- 24579317
TI  - Neuroanatomy and physiology.

PMID- 24579316
TI  - [The exploration and practice of production of transgenic zebrafish into
      undergraduate student gene engineering experimental teaching].
AB  - The preparation of transgenic animals is one of the core technology and critical
      achievement of gene engineering. However, it has not been reported that the gene
      engineering experimental course of undergraduate students in universities of
      mainland China has carried out the preparation of transgenic animals. In this
      paper, the authors took the advantage of scientific research platform, introduced
      the transgenic zebrafish technology to gene engineering experimental course of
      undergraduate students, and explored and practiced related teaching model, which
      had achieved good results and had great value to popularize.

PMID- 24579318
TI  - Clinical and ethical dimensions of an innovative approach for treating mental
      illness: a qualitative study of health care trainee perspectives on deep brain
      stimulation.
AB  - BACKGROUND: The acquisition of knowledge and application of critical thinking
      skills are required to tackle the clinical and ethical dimensions of new
      approaches and technologies. Health care trainees rely partly on their training
      to manage, reason and reflect on the ethical uncertainties of innovations and new
      technologies. Deep brain stimulation (DBS) is neurosurgery involving the
      implantation of electrodes into deep brain nuclei and is approved for Parkinson's
      disease and other motor disorders. Experimental uses of DBS are emerging in
      refractory obsessive compulsive disorder and depression. METHODS: We conducted a
      qualitative interview-based study to gather the perspectives of health care
      trainees from different disciplines on the clinical and ethical issues associated
      with DBS in psychiatric disorders. RESULTS: First impressions about the use of
      DBS in mental illness were mixed. We identified factors influencing impressions
      about DBS and information missing that compounded uncertainty about long-term
      outcomes and effects on other physical or psychological systems. Participants
      revealed nascent exploration of the ethical issues of DBS. They emphasized the
      obligations of health care providers to manage ethical problems and supported
      patient autonomy in guiding choice, even when choosing innovative approaches.
      DISCUSSION: We discuss trainee expectations about evidence in decision making and
      the role of ethics education.

PMID- 24579319
TI  - [The expert patient].

PMID- 24579320
TI  - [What good use of antidepressants?].

PMID- 24579321
TI  - [Why must we vaccinate and get vaccinated against flu!].

PMID- 24579322
TI  - [Circulatory support in cardiology].
AB  - Mechanical cardiac assist had progressively changed. Emergency depends of
      INTERMACS classification. The clinical evolution of patients under cardiac assist
      determines patient follow up: long duration mechanical support (and not
      "destination therapy"), recovery and weaning or planned heart transplantation. In
      case of emergency, extracorporeal membrane oxygenation allowed to stabilize
      patients and oriented them to one of these options.

PMID- 24579323
TI  - [Novel uses of rituximab].
AB  - Since its approved by HAS in 1998, the use of rituximab increases every year.
      Marketed in France under the name MabThera, rituximab is used primarily in the
      treatment of B-cell malignancies including follicular lymphoma, diffuse large B
      cell lymphoma and chronic lymphocytic leukemia and corresponding to the three
      main indications for treatment. However, given its action on B cells, rituximab
      also proves to be effective in rheumatoid arthritis. By extension as anti-B-cell,
      rituximab is actually used in other autoimmune diseases: in autoimmune cytopenias
      as idiopathic thrombocytopenic purpura and hemolytic anemia, in vasculitis, or
      multiple sclerosis, it is also used in organ transplantation as kidney in
      prophylaxy to rejection and treatment of EBV-mediated complications.

PMID- 24579324
TI  - [Human bite wound].

PMID- 24579325
TI  - [The content curation with Scoop.it].

PMID- 24579326
TI  - [Loss of hbs antigen after treatment with analogues: infrequent but stable and
      beneficial].

PMID- 24579327
TI  - [Not Available].

PMID- 24579328
TI  - [Breast cancer: major therapeutic advances but mortality remains high].

PMID- 24579329
TI  - [Epidemiology of breast cancer].
AB  - Each year, 50,000 new cases of breast cancer are diagnosed in France and 11,000
      women die from it. After a sharp increase, partly explained by the screening
      program implementation, the incidence rate has decreased for few years. Since the
      2000s, the mortality rate has been declining steadily. Many risk factors for
      breast cancer are known or suspected. Endogenous hormonal factors (age at
      menarche, menopause, first pregnancy, lactation, number of children) and
      exogenous (hormone replacement therapy, contraception...) are known risk factors.
      The lifestyle (weight, diet, physical activity, night work), the family past
      history as well as environmental pollution may also play a role in breast cancer
      development. Even if all these factors have individually only a low impact on the
      occurrence of breast cancer, their effects are additive. However, many patients
      who will develop breast cancer do not present currently known risk factors.

PMID- 24579330
TI  - [Populations with risk for breast cancer].

PMID- 24579331
TI  - [Screening for breast cancer: worries about its effectiveness].
AB  - Breast cancer screening in France is done though two parallel systems:
      individualized screening and a national programme of organized screening. The
      latter is free of charge and manages a double-reading of mammography films. Since
      2004, a steadily greater proportion of French women 50 to 74 years of age
      participate to the national programme. Justification of screening in France is
      based on Swedish randomised trials that documented the ability of mammography
      screening to reduce the risk to die from breast cancer. However, since 3 years, a
      growing number of studies indicate that screening seems not to have much
      influence on the incidence of advanced breast cancer and on mortality from breast
      cancer Moreover, numerous breast cancers are detected that would have never
      clinically surfaced and would have never been life threatening (overdiagnosis).
      In view of current doubts, it is better to inform women on health benefits,
      limitations and possible side effects of mammography screening. For women willing
      to be screened, it is recommended to invite them to participate to the national
      programme.

PMID- 24579332
TI  - [Breast cancer imaging].
AB  - Imaging of breast cancer is multimodal. Mammography uses X-rays, the development
      of digital mammography has improved its quality and enabled implementations of
      new technologies such astomosynthesis (3D mammography) or contrast-enhanced
      digital mammography. Ultrasound is added to mammography when there is need to
      improve detection in high-density breast, to characterize an image, or guide
      apuncture or biopsy. Breast MRI is the most sensitive imaging modality. It
      detects a possible tumor angiogenesis by highlighting an early and intense
      contrast uptake. This method has an excellent negative predictive value, but its
      lack of specificity (false positives) can be problematic, thus it has to be
      prescribed according to published standards. An imaging breast screening report
      must be concluded by the BI-RADS lexicon classification of the ACR and
      recommendations about monitoring or histological verification.

PMID- 24579333
TI  - [Diagnostic approach for breast cancer classification].
AB  - The pathologist is involved at various steps in the management of a patient with
      breast cancer and in the therapeutic decision. First, the pathologist confirms a
      diagnosis of malignancy on cytology specimens, microbiopsies and surgical
      specimens. During the surgery, through the frozen section, the pathologist
      specifies the surgical limits and collects specimens for research purposes. Then
      the pathologist evaluates the parameters needed to establish the final diagnosis,
      the prognosis and the identification of predictive factors, using ancillary
      techniques such as immunohistochemistry, in situ hybridization or molecular
      techniques. Mandatory elements to be included in the final pathological report
      are size, histological type, SBR grade modified by Elston and Ellis, the presence
      or absence of vascular or lymphatic peritumoral emboli (prognostic parameters),
      the status of resection margins (local relapse risk) and the status of hormonal
      receptor and HER2 (predictive parameters).

PMID- 24579334
TI  - [Triple-negative breast cancer].

PMID- 24579335
TI  - [Breast cancer: a multidisciplinary management].

PMID- 24579336
TI  - [Breast cancer surgery].
AB  - The surgery for breast cancer is frequently the first step in a multi
      disciplinary care. It allows for local control, but also to establish crucial
      prognostic factor indicating potential adjuvant therapy. The current trend s
      towards de-escalation of surgical treatment for reducing the functional and
      aesthetic morbidity. At the local level, this de-escalation has been made
      possible by performing most often breast conservative surgery because of the
      development of oncoplastic techniques, but also because of neoadjuvant
      chemotherapy. At the axillary level, the reduction of morbidity has been made
      possible by the advent of the sentinel node biopsy which is more and more
      indicated year after year.

PMID- 24579337
TI  - [Breast reconstruction after mastectomy: preoperative information is crucial].

PMID- 24579338
TI  - [Breast cancer radiotherapy: current changes].

PMID- 24579339
TI  - [Breast cancer adjuvant endocrine treatment].
AB  - Endocrine treatment of early stage breast cancer may be summarized in two
      settings. (1) Early breast cancer, premenopausal women: tamoxifen; ovarian
      suppression is an acceptable option. (2) Early breast cancer, menopausal women:
      aromatase inhibitors, for at least 2 to 3 years; extended treatment beyond 5
      years of tamoxifen may be discussed.

PMID- 24579340
TI  - [Medical treatment of breast cancer: chemotherapy and tailored therapy].
AB  - The utility of adjuvant chemotherapy is clearly demonstrated because she
      significantly improved relapse and mortality. Globally, we report a one-third
      breast cancer mortality reduction. Nevertheless, the absolute or individual
      benefit is uncertain and the final decision depends on benefit-risk balance,
      integrating tumor biologic characteristics and comorbidities. The most effective
      regimen must contain an anthracycline and a taxane. This regimen must be proposed
      if chemotherapy indication is considered: this concerns the majority of triple
      negative and HER2-positive cancer For hormone-receptor-positive and HER2-negative
      breast cancer, the decision of adjuvant or not (in addition to hormonal therapy)
      is most difficult, particularly for grade 2 tumors. The trastuzumab is an
      essential treatment for HER2-positive breast cancer, because this tailored
      therapy has considerably improved the prognosis.

PMID- 24579341
TI  - [Supervision after breast cancer treatment].
AB  - Breast cancer screening and therapeutic advances have significantly decreased
      breast cancer mortality. Nearly 80% of patients with a localized disease will
      experience a prolonged survival and the organization of their monitoring is
      critical to early detection of local or metastatic relapse. Annual mammography is
      recommanded for the follow up and no further imaging examination is routinely
      necessary. Early diagnosis of metastatic relapse has not demonstrated evidence of
      survival benefit. However, treatments are not without toxicities and data about
      long-term complications are missing. The socio-economic consequences for these
      patients need to be evaluated and cardiovascular toxicities of chemotherapy and
      hormonal therapy are probably underestimated.

PMID- 24579342
TI  - [Epidemiological news in cannabis].
AB  - Cannabis is by far the most common illicit drug in France. Among 15-64 years,
      32.1% have already experienced it and 8.4% declare they have used it at least
      once during the past twelve months. In Europe, France is one of the countries
      with the highest prevalence. Males are markedly more often cannabis users than
      females and this gender gap tends to increase with the level of use. During the
      last two decades, the part of the population having tried cannabis did not stop
      increasing, under the influence of a generalization of the cannabis experience
      among young people. However, cannabis last year prevalence is rather stable since
      2000. Cannabis lifetime use is very rare at the beginning of middle school (1.5%
      in sixth grade at age 11) but increases in the following years (11% of the pupils
      of the eighth grade, 24% of the pupils of the ninth grade). Cannabis use at a
      younger age is related to subsequent onset of cannabis related problems.
      Adolescent and young adults from high socioeconomic status (SES) more often try
      cannabis than young people from lower SES. However, cannabis regular use is
      associated with bad school results, truancy and early school leaving, and with a
      lower SES. Young people from high SES indeed dispose of greater sociocultural
      resources to master and regulate their consumption and are more often conscious
      of their interest not to be tipped over in problematic use.

PMID- 24579343
TI  - [Cannabis: the gateway theory or comorbid substance use?].

PMID- 24579344
TI  - [Psychiatric complications of cannabis use].
AB  - Cannabis is the most widely used illicit substance, especially among young
      people. Cannabis use is extremely commonplace and frequently comorbid with
      psychiatric disorders that raise questions about the etiology. The use of
      cannabis is an aggravating factor of all psychiatric disorders. Psychiatric
      complications are related to the age of onset, duration of exposure and
      individual risk factors of the individual (mental and social health). The panic
      attack is the most common complication. The link with psychosis is narrow that
      leads to increased prevention for vulnerable populations. Cannabis is also an
      indicator of increased depressive vulnerability and an aggravating factor for
      bipolar disorder.

PMID- 24579345
TI  - [Cognitive impairment of cannabis use].

PMID- 24579346
TI  - [Somatic consequences of cannabis use].
AB  - Cannabis can have negative effects in its users, and a range of acute and chronic
      health problems associated with cannabis use has been dentified. Acute cannabis
      consumption is rarely lethal but it is associated with an increased risk of motor
      vehicle accident because of longer reaction time or impaired motor coordination.
      Chronic effects of cannabis use include generally cardiovascular and respiratory
      consequences but there are also oral, gastrointestinal, cutaneous and mucous,
      metabolic, gynecologic and obstetrical, sexual consequences, and cancer But
      associated tobacco smoking or other potential confounders may explain part of
      those somatic consequences.

PMID- 24579348
TI  - [How to detect teenagers' cannabis use and what needs to be done?].
AB  - Adolescence is a period of confrontation and initiation to psychoactives drugs.
      Teenager's substance disorder remains an important concern for families and
      public authorities. The seriousness of consequences due to cannabis use, both on
      the health and social points, depends on the age of first use, the duration of
      use and the user himself. Teenagers, who do not often request to be taken care,
      are a population who has difficulty to access to medical treatment, even if the
      offer of medical treatment has increased. It is necessary to develop an early
      detection among vulnerable populations like teenagers, to train first aid
      operators to early detection strategies, as well as to increase the knowledge of
      the care system to improve teenagers' orientation in the care system.

PMID- 24579347
TI  - [Cannabis and pregnancy].

PMID- 24579350
TI  - [Doctors and nurse(s)...overseas].

PMID- 24579349
TI  - [Treatment of cannabis dependence].

PMID- 24579351
TI  - [Myelodysplastic syndromes].

PMID- 24579352
TI  - [The methodology of experimental and clinical research].

PMID- 24579353
TI  - [Prosthesis and osteosynthesis].

PMID- 24579354
TI  - [Did workers have rights in the days of the pharaohs?].

PMID- 24579355
TI  - [Effect of transcutaneous electrical stimulation of Zusanli (ST 36) and Liangqiu
      (ST 34) combined with general anesthesia on pain and gastrointestinal symptoms in
      patients undergoing gynecological laparoscopic operation].
AB  - OBJECTIVE: To observe the effects of transcutaneous acupoint electrical
      stimulation (TAES) combined with general anesthesia (acupuncture analgesia
      combined with general anesthesia) on postoperative pain, nausea and vomiting and
      exhausted defecation symptoms in patients undergoing gynecological laparoscopic
      operation. METHODS: Sixty patients with gynecological laparoscopic operation were
      randomly divided into TAES group and control group, with 30 cases in each group.
      Patients of the control group received simple general anesthesia and those of the
      TAES group were treated with general anesthesia and TAES of bilateral Zusanli (ST
      36) and Liangqiu (ST 34) . Visual Analogue Scale (VAS) was used for measuring the
      patients' pain reaction at 8 h, 24 h and 72 h after surgery. Symptoms of
      patients' nausea and vomiting, post-operation exhaust and defecation time were
      recorded after operation. RESULTS: The VAS scores at time-points of 8 h, 24 h and
      72 h and nausea level in the TAES group were significantly lower than those of
      the control group (P < 0.01, P < 0.05). The vomiting severity of the TAES group
      was also relatively lower in comparison with the control group, but without
      significant difference between the two groups (P > 0.05). The post-operation
      exhaust and defecation time of patients in the TAES group apparently appeared
      earlier than those of patients in the control group (P < 0.01). CONCLUSION: TAES
      combined with general anesthesia is effective in reducing post-operative pain and
      nausea, and improving gastrointestinal function in patients undergoing
      laparoscopic operation.

PMID- 24579356
TI  - [Effects of electroacupuncture intervention on neurological function, blood
      glucose and insulin levels in rats with focal cerebral ischemia].
AB  - OBJECTIVE: To observe the effect of electroacupuncture (EA) intervention on
      dynamic changes of neurological function, blood glucose and insulin levels in
      rats with focal cerebral ischemia (CI), so as to explore its mechanism underlying
      improvement of ischemic cerebral vascular disease. METHODS: Male Wistar rats were
      randomly divided into four groups: normal, sham-operation (sham), model and EA.
      CI model was induced by middle cerebral artery occlusion (MCAO). The four groups
      were further randomized into 5 subgroups according to time-points of MCAO: 6
      hour, day 1, day 3, day 7 and day 14 (8 rats/ group). EA (2 Hz/15 Hz, 1 mA) was
      applied to bilateral "Neiguan" (PC 6) and "Quchi" (LI 11) for 30 min, once daily
      for 1 day to 14 days. Neurological impairment was evaluated by Zea Longa 5-point
      scoring system. Local cerebral blood flow (LCBF) of the cerebral pia mater was
      determined using Laser Doppler Flowmetry. The levels of abdominal cavity venous
      blood glucose and serum insulin were measured by using a glucose meter and
      radioimmunoassay, respectively. RESULTS: In comparison with the normal and sham
      groups, the rats' body weights and LCBF levels at time-points of day 1, 3, 7 and
      14, and blood glucose and serum insulin levels at most time-points of 6 h, day 1,
      3, 7 and 14 after CI were significantly decreased in the model group (P < 0.05),
      and neurological scores at time-points of 6 h, day 1, 3, 7 and 14 were markedly
      increased in the model group (P < 0.05). After EA intervention, compared with the
      model group, the rats' body weights at time points of day 3, 7 and 14, LCBF
      levels on day 7 and 14, blood glucose on day 14, and serum insulin contents at
      time-points of day 1, 3, 7 and 14 were considerably increased in the EA group (P
      < 0.05), while Zea Longa scores at time-points of day 3 and 7 were evidently
      decreased in the EA group (P<0.05). CONCLUSION: EA intervention is effective in
      improving neurological function in CI rats, which is probably associated with its
      functions in improving cerebral blood flow, and up-regulating blood glucose and
      insulin levels.

PMID- 24579357
TI  - [Effect of electroacupuncture intervention on expression of extracellular matrix
      collagen and metabolic enzymes].
AB  - OBJECTIVE: To observe the effect of electroacupuncture (EA) at "Dazhui" (GV 14)
      on the contents of extracellular matrix (ECM), collagen type II (COL-II),
      collagen type V (COL-V), matrix metalloproteinase (MMP)-13, tissue inhibitor of
      metalloproteinase (TIMP)-1 in rats with cervicovertebral disc degeneration so as
      to explore its mechanism underlying relief of intervertebral disc degeneration.
      METHODS: A total of 28 SD rats were randomly divided into sham group (n = 7),
      model group (n = 7), EA group (n = 7) and medication group (n = 7). The model of
      cervical intervertebral disc degeneration was established by trans-section of the
      deep neck splenius, the longest muscles of head, neck costocervicalis, head semi
      spinatus muscle, supraspinous ligament and interspinal ligaments of cervical 2-7
      segments, etc. to produce imbalance between the dynamic and static force. EA was
      applied to "Dazhui" (GV 14) for 30 min, once daily for 28 days, with a 2 days'
      interval between two courses. Animals of the medication group were treated by
      oral administration of meloxicam tablets (0.75 mg/kg) once daily for 28 days,
      with a 2 days' interval between two courses. Immunohistochemistry was used to
      measure the expression of ECM, COL- II, COL-V, MMP-13 and TIMP-1 in the
      cervicovertebral disc tissue. RESULTS: Compared with the sham group, the
      expression levels of ECM and COL-II proteins in the cervicovertebral disc tissue
      were significantly decreased in the model group (P < 0.01), while COL-V and MMP
      13 expression levels in the model group were significantly increased (P < 0.01, P
      < 0.05). Compared with the model group, both ECM and COL-Il expression levels
      were considerably increased in the EA group and medication group (P < 0.01),
      while COL-V and MMP-13 expression levels were considerably down-regulated (P <
      0.01, P < 0.05). No significant differences were found among the four groups in
      TIMP-1 expression levels (P > 0.05). CONCLUSION: EA of "Dazhui" (GV 14) can
      effectively regulate extracellular matrix system in rats with cervical
      intervertebral disc degeneration, which is possibly related to its effect in
      relieving cervical spondylosis.

PMID- 24579358
TI  - [Dendritic projections from meridian-related motoneurons to sympathic preganglion
      neurons in the spinal cord of rats].
AB  - OBJECTIVE: Previous studies indicated a close involvement of reflex activities of
      motoneurons in the spinal cord in the mechanism of meridian phenomena. The
      present study was designed to investigate the dendrite projections of meridian
      related motoneurons among the motoneurons and sympathetic preganglionic neurons
      in the spinal cord. METHODS: A total of 41 Sprague-Dawley rats were used in the
      present study. Cholera toxin B-subunit conjugated horseradish peroxidase (CB-HRP)
      containing 1.0% HRP was respectively injected to acupoint "Chengman" (ST 20),
      "Liangmen" (ST 21), "Guanmen" (ST 22), "Taiyi" (ST 23), "Huaroumen" (ST 24),
      "Tianshu" (ST 25) and "Wailing" (ST 26) of the Stomach Meridian, and "Ganshu" (BL
      18), "Danshu" (BL 19), "Pishu" (BL 20), "Weishu" (BL 21) and "Sanjiaoshu" (BL 22)
      of the Bladder Meridian, and "Daimai" (GB 26), "Wushu" (GB 27), "Weidao" (GB 28),
      "Juliao" (GB 29), "Huantiao" (GB 30), "Fengshi" (GB 31), "Zhongdu" (GB 32),
      "Xiyangguan" (GB 33) and "Yanglingquan" (GB 34) of the Gallbladder Meridian (for
      labeling preganglionic neurons), and the celiac ganglion and superior mesenteric
      ganglion for labeling sympathetic preganglionic neurons. Three days after
      injection, the animals anesthetized were transcardia-cally perfused with 1.5%
      paraformaldehyde, the spinal cord was removed to be fixed routinely and then cut
      into sections for observing the labeled cells under microscope. RESULTS: In the
      ipsilateral ventral horn of the spinal cord, the motoneurons retrogradely labeled
      by CB-HRP formed dendritic projections oriented only to those motoneurons
      innervating the same meridian. In the longitudinal sections of spinal cord, the
      labeled motoneurons formed a bead-like column with a prominent network of
      longitudinal dendrites connecting the motoneurons innervating acupoints from the
      same meridian. In the transverse sections of spinal cord, two groups of dendrites
      from the labeled motoneurons projected to the identified sympathetic
      preganglionic regions: one group extended dorsolateraly to the intermediolateral
      gray, another group extended intermediolateraly toward the central canal. In rats
      with injection of CB-HRP into both acupoint regions and ipsilateral celiac
      ganglion, the dendrites originated from the labeled motoneurons projected
      directly to the labeled sympathetic preganglionic neurons. CONCLUSION: Each of
      the ST, BL and GB meridians is innervated by a specific group of motoneurons in
      the spinal cord. The motoneurons form a column with distinct border in the
      ventral horn of spinal cord, and the dendritic projections from the motoneurons
      oriented only to those innervating the same meridian. The dendrites from the
      meridian-related motoneurons can specifically project to the sympathetic
      preganglionic neurons at the thoracolumbar level.

PMID- 24579359
TI  - [Experimental study on functional connection between the lung and large intestine
      meridians in the rat: cross-talk between the lung and large intestine meridians].
AB  - OBJECTIVE: According to the theory of traditional Chinese medicine about "close
      association between the lung and the large intestine", the present study was
      designed to investigate the functional relationship between the Lung and Large
      Intestine Meridians and the colorectum by using electrophysiological methods.
      METHODS: A total of 40 SD rats were used in the present study. Under anesthesia,
      the cardiopulmonary branch of the left sympathetic nerve (CPSN) was separated for
      recording the electrical activities with a pair of platinum wire electrodes.
      Intra-colorectal pressure was recorded using a water-balloon inserted into the
      anus and connected to a pressure-transducer for observing rectocolonic pressure
      changes (mobility). Electroacupuncture (EA) stimulation was applied to bilateral
      "Taiyuan" (LU 9)- "Jingqu" (LU 8) of the Lung Meridian, "Yangxi" (LI 5)-"Pianli"
      (LI 6) of the Large Intestine Meridian, and "Shangjuxu" (ST 37)-"Zusanli" (ST 36)
      of the Stomach Meridian, respectively. Colorectal distension (CRD, visceral pain
      stimulation, 60 mmHg and 80 mmHg) was performed using an air-balloon for
      observing its influence on EA stimulation of LU 9- LU 8 induced changes of
      electrical activities of CPSN. RESULTS: Under anesthesia conditions, no
      spontaneous electrical activities of the CPSN were found in rats. After EA
      stimulation (3 times of the threshold intensity) of the bilateral "Taiyuan" (LU
      9)- "Jingqu" (LU 8) of the Lung Meridian, and "Yangxi" (LI 5)-"Pianli" (LI 6) of
      the Large Intestine Meridian, the evoked discharge numbers of the cardiopulmonary
      sympathetic nerve were (11.26 +/- 2.34) and (10.73 +/- 2.62) spikes,
      respectively, without significant differences between the two groups (P > 0.05).
      Compared with pre-stimulation, the colorectal motility (amplitudes of the intra
      colorectal pressure waves) was obviously increased following EA stimulation of LU
      9-LU 8 of the Lung Meridian, LI 5-LI 6 of the Large Intestine Meridian and
      "Shangjuxu" (ST 37)-"Zusanli" (ST 36) , Lower-Ho (Sea) acupoints of the Large
      Intestine Meridian (P < 0.05). After CRD stimulation at 60 mmHg and 80 mmHg, the
      LU 9- LU 8-stimulation evoked discharge rates of CPSN were reduced by 43.46% and
      67.42%, respectively. CONCLUSION: EA stimulation of LU 9- LU 8 of the Lung
      Meridian and LI 5-LI 6 of the Large Intestine Meridian can activate discharges of
      CPSN, and increase the colorectal motility in the rat. CRD stimulation inhibits
      the activated effect of EA on electrical activities of CPSN. These results show a
      functional communication or cross-talk between the lung and the colorectum.

PMID- 24579360
TI  - [Effect of electroacupuncture of "Fenglong" (ST 40) on levels of blood lipid and
      macrophage TNF-alpha and IL-6 in hyperlipidemic rats].
AB  - OBJECTIVE: To observe the effect of electroacupuncture (EA) stimulation of
      "Fenglong" (ST 40) on blood lipid contents and inflammatory factor levels in
      hyperlipemia rats so as to elucidate its mechanism underlying improvement of
      hyperlipemia. METHODS: Fifty male SD rats were randomized into 5 groups: normal,
      model, diet -control, EA intervention (EA), diet-control + EA groups, with 10
      rats in each group. Hyperlipemia model was established by feeding the animals
      with high-fat diet for 30 days. After modeling, rats in the diet-control group
      were fed with routine fodder. EA was applied to bilateral "Fenglong" (ST 40) for
      30 min, once daily for 30 days. Following intraperitoneal injection of 1640
      culture fluid, the peritoneal fluid was collected and centrifuged for extracting
      macrophages. Flow cytometry (FCM) was employed to determine the levels of tumor
      necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) after adding fluoresce
      labeled antibodies. RESULTS: The contents of serum TC and LDL-C were remarkably
      higher and HDL-C level was significantly lower in the model group than in the
      normal group (P < 0.01). After EA intervention, serum TC and LDL-C showed an
      apparent decrease (P < 0.01). Compared with the normal group, percentages of CD11
      b, TNF-alpha and IL-6 were significantly increased in the model group (P < 0.01),
      while in comparison with the model group, percentages of CD11 b in both EA and
      diet-control + EA groups, TNF-alpha and IL-6 percentages of macrophages in the
      diet-control, EA and diet-control + EA groups were notably decreased (P < 0.05, P
      < 0.01). The effects of the diet-control + EA group were considerably superior to
      those of the diet-control group in lowering CD11 b, TNF-alpha and IL-6
      percentages (P < 0.05, P < 0.01). No significant differences were found between
      the diet-control and EA groups in the aforementioned indexes (P > 0.05). CD11 b
      level indicates changes of macrophage level due to its specific marker character.
      CONCLUSION: EA stimulation of "Fenglong" (ST 40) is effective in lowering serum
      TC, LDL-C, and macrophage TNF-alpha and IL-6 levels in hyperlipemia rats.

PMID- 24579361
TI  - [Effects of electroacupuncture of "Guanyuan" (CV 4)-"Zhongji" (CV 3) on ovarian
      P450 arom and P450c 17alpha expression and relevant sex hormone levels in rats
      with polycystic ovary syndrome].
AB  - OBJECTIVE: To observe the effect of electroacupuncture (EA) on ovarian P 450 arom
      and P 450 c 17 alpha (aromatases) expression and related sex hormone levels in
      polycystic ovary syndrome (PCOS) rats. METHODS: Thirty SD rats were randomly
      divided into normal control group, model group and EA group (10 rats/group). PCOS
      model was made by intragastric administration of letrozole at 1 mg/kg per day for
      consecutive 21 days. "Guanyuan" (CV 4) and "Zhongji" (CV 3) acupoints were
      stimulated 20 min by EA (2 mA, 2 Hz), once daily for consecutive 14 days. The
      damp ovarian weight was weighed and the pathological changes of the ovarian
      tissue were observed after H. E. staining. Ultrastructural changes of the ovarian
      tissue were observed by transmission electron microscope. Immunohistochemical
      staining was adopted to detect ovarian follicle granulosa cell P 450 arom and
      follicle membrane cell P 450 c 17 alpha expression. The contents of estradiol (E
      2), estrone (E 1), androstenedione (ASD), testosterone (T), follicle-stimulating
      hormone (FSH) and luteinizing hormone (LH) in the ovarian tissue were measured by
      ELISA. RESULTS: Compared with the normal group, there was a significant increase
      in the damp weight of both left and right ovarian tissues in the model group (P <
      0.01). After EA, the ovarian weight was remarkably reduced (P < 0.01).
      Pathological changes of the ovarian tissue such as thickening of the superficial
      albugineous coat of the ovary, thinning of the granular cell layer, and
      disappearance of the intraovular oocytes and coronaradiata under light
      microscope, and mitochondrion swelling, fracture or disappearance of
      mitochondrial cristae, and enlargement of the endoplasmic reticulum, etc. after
      modeling were obviously improved in the EA group. In comparison to the control
      group, the expression of the follicle granulosa cell P450 arom was significantly
      down-regulated and that of follicle membrane cell P 450 c 17 alpha was
      significantly upregulated in the model group (P < 0.01). After EA intervention
      these changes were obviously reversed (P < 0.05, P < 0.01). In the model group,
      there was a significant increase in the levels of ASD, T and LH in the ovarian
      tissues (P < 0.01) and a marked decrease in the contents of ovarian E 1 and E2 (P
      < 0.01) in comparison to the control group. After EA, the ovarian ASD, T and LH
      levels were notably decreased (P < 0.05, P < 0.01) and the E 1 and E 2 levels
      apparently increased (P < 0.01) compared with the model group. CONCLUSION: EA can
      improve letrozole-induced pathological changes of ovarian morphology and
      ultrastructure and obviously promote P 450 arom expression in the follicle
      granulosa cell layer and inhibit P 450 c 17 alpha expression in the follicle
      membrane cell layer, as well as regulate sex hormone levels in PCOS rats,
      facilitating the normal transformation of ovarian androgen to estrogen and
      restoring the local endocrine disorders.

PMID- 24579362
TI  - [Anatomic structure of "Shaoze" (SI 1), "Qiangu" (SI 2), "Houxi" (SI 3), "Yanggu"
      (SI 5) and Xiaohai" (SI 8) regions of Hand-Taiyang Meridian in the rabbit's
      forelimb].
AB  - OBJECTIVE: To observe the anatomic structure of the Five Shu-acupoints: "Shaoze"
      (SI 1) ,"Qiangu" (SI 2), "Houxi" (SI 3),"Yanggu" (SI 5) and "Xiaohai" (SI 8)
      regions of the Taiyang Meridian in the rabbit's forelimb. METHODS: Thirty rabbits
      (half male and half female) were used in the present study. The Five Shu
      acupoints regions were located first based on the atlas of rabbits, stimulated by
      needling and confirmed later by using an electronic acupoint detector. Under
      anesthesia, the rabbit was perfused with warm normal saline via the common
      carotid artery and the internal jugular vein, followed by arterial perfusion of
      dental base acrylic resin powder(30 g), dibutylphthalate(6 mL), red couring agent
      liquid for denture acrylic and acetoacetate (2 mL), respectively; and venous
      perfusion of 30% gelatin (filtered) and black ink (filtered) and formaldehyde
      (8%). After fixing in 8% formaldehyde for 10 days, the rabbit's forelimb
      containing the aforementioned Five Shu-acupoints were carefully dissected layer
      by layer, followed by observing the local anatomic structure under microscope.
      RESULTS: The superficial layers of these acupoint regions mainly contained the
      basilic vein and its branches, and the superficial branch of the ulnar nerve. The
      deep layers chiefly comprised of the ulnar artery, the ulnar vein and their
      branches, and the ulnar nerve. CONCLUSION: In "Shaoze"(SI 1 ), "Qiangu" (SI 2),
      "Houxi" (SI 3), "Yanggu" (SI 5) and "Xiaohai" (SI 8) acupoint regions, the ulnar
      artery, basilic vein, ulnar vein and their branches, the ulnar nerve and its
      superficial branches are found, which constitute the morphological basis of the
      five acupoints of the Hand-Taiyang Meridian for treating some related clinical
      disorders.

PMID- 24579363
TI  - [Effects of electroacupuncture stimulation of "Neiguan" (PC 6) and "Shenmen"
      (HT7) on contents of 5-hydroxytryptamine in hypothalamic paraventricular nucleus
      region and serum in hyperlipidemia rats with acute myocardial infarction].
AB  - OBJECTIVE: To observe the effects of electroacupuncture (EA) stimulation of
      "Neiguan"(PC 6) and "Shenmen" (HT 7) on 5-hydroxytryptamine (5-HT) levels in the
      paraventricular nucleus (PVN) region of hypothalamus and serum in hyperlipidemia
      rats with acute myocardial infarction (AMI). METHODS: A total of 80 SD rats with
      hyperlipidemia were used in the present study. Among them, 20 rats were randomly
      selected to be the sham-operation group, and the rest 60 cases were used to make
      the AMI model by occlusion of the anterior descending branch of the left coronary
      artery. The 60 rats who were identified to be successful in AMI were randomly
      divided into model group, EA-PC 6 group and EA-HT 7 group (20 rats/group). EA (2
      Hz, 2 mA) was applied to bilateral PC 6 and HT 7 for 20 min, once daily for 5
      days. The contents of 5-HT of hypothalamic PVN region and serum were examined by
      enzyme linked immunosorbent assay (ELISA) and radioimmunoassay, respectively.
      RESULTS: Following AMI, marked myocardial injury (swelling, breakage,
      disappearance of local transverse striations and necrosis of myocytes) with
      infiltration of neutrophil granulocytes was found in the model group, while in
      both EA-PC 6 group and EA-HT 7 group, moderate swelling (no breakage) of fewer
      myocardial fibers with mild infiltration of neutrophil granulocytes was found,
      indicating a marked improvement of myocardial injury after EA treatment. Compared
      with the sham-operation group, the content of 5-HT was obviously decreased in the
      hypothalamic PVN region and significantly increased in serum in the model group
      (P < 0.01). After EA intervention, the content of 5-HT was considerably up
      regulated in the hypothalamic PVN region and apparently down-regulated in serum
      in both EA-PC 6 and EA-HT 7 groups in comparison with the model group (P < 0.01).
      No significant differences were found between EA-PC 6 and EA-HT 7 groups in
      regulating hypothalamic and serum 5-HT levels (P > 0.05). CONCLUSION: EA
      stimulation of both PC 6 and HT 7 can relieve acute ischemic injury of the
      myocardium in hyperlipidemia rats, which is probably partially related to its
      effect in promoting the release of 5-HT from the hypothalamic PVN region.

PMID- 24579364
TI  - [Effect of acupoint heat-sensitive moxibustion intervention on serum osteopontin
      and matrix metalloproteinase-3 in patients with acute knee pain].
AB  - OBJECTIVE: To observe the clinical effect of acupoint heat-sensitive moxibustion
      for acut knee arthralgia and to analyze its effect on serum osteopontin (OPN) and
      matrix metalloproteinase-3 (MMP-3) contents in patients with knee osteoarthritis
      so as to study its mechanism underlying improving arthralgia. METHODS: One
      hundred and forty-four patients with acute knee knee osteoarthritis were randomly
      allocated to acupoint heat-sensitive moxibustion (moxibustion),
      electroacupuncture (EA) and medication groups. Patients of the moxibustion group
      were treated by suspended moxibustion over bilateral Weizhong (BL 40) for 40 min
      each point, once daily for 15 days. Patients of the EA group were treated by EA
      stimulation of Neixiyan (EX-LE 4), Dubi (ST 35), Xuehai (SP 10) and Liangqiu (ST
      34) for 30 min, once daily for 15 days; and those of the medication group treated
      by oral administration of Sanqi Tongshu capsules (Panax Notoginseng, etc. used
      for promoting blood circulation and removing blood stasis), 3 times daily for 15
      days. Serum OPN and MMP-3 levels were detected with ELISA. RESULTS: Following the
      treatment, of the 50, 50 and 44 cases in the moxibustion, EA and medication
      groups, 24, 20 and 14 were excellent, 18, 16 and 13 were good in therapeutic
      effect, 7, 4, and 3 were effective, and 1, 10, and 14 invalid, with the excellent
      and good rates being 84%, 72.0% and 61.4%, respectively. Serum OPN content of the
      moxibistion and EA groups, and serum MMP-3 content of the moxibustion group were
      reduced considerably in comparison with pre-treatment in the same one group (P <
      0.01), while serum OPN level of the medication group and MMP-3 of the EA group
      were decreased slightly. The effect of moxibustion was evidently superior to that
      of medication in lowering serum OPN level (P < 0.05) and superior to that of both
      EA and medication in lowering serum MMP-3 content (P < 0.05). CONCLUSION:
      Acupoint heat-sensitive moxibustion has a good therapeutic effect in relieving
      acute knee arthralgia, which may be related to its effects in decreasing serum
      OPN and MMP-3 levels.

PMID- 24579365
TI  - [Relationship between patients' sensitivity to moxibustion stimulation and
      clinical effect in the treatment of peripheral facial palsy].
AB  - OBJECTIVE: To compare the outcome difference between the heat-sensitive and non
      sensitive moxibustion stimulation of Yifeng (TE 17) in the treatment of
      peripheral facial palsy. METHODS: A total of 43 patients with peripheral facial
      paralysis were divided into heat-sensitive moxibustion (n = 21) and non-sensitive
      moxibustion (n = 22) groups in accordance with their reactions to moxa-heat
      stimulation. Mild moxibustion was applied to bilateral Yifeng (TE 17) for 45
      minutes, followed by mild acupuncture stimulation of Cuanzhu (BL 2), Yangbai (GB
      14), Sibai (ST 2), Hegu (LI 4), etc. Moxibustion treatment was conducted once
      daily for 10 days, and acupuncture treatment given once daily for 20 days (with 2
      days interval between every 10 days). Following moxibustion, if the patient felt
      regional heat penetrating to the deep tissue, extending peripherally, or
      propagating to other part of the body, or felt mild warm in the stimulated region
      but warmer in the slightly distant part, or felt mild warm on the skin surface
      but warmer in the deep tissue, it was considered to be heat-sensitivity. Patients
      with occurrence of heat-sensitivity being equal to and more than 3 times during
      the 10 sessions of treatment were assigned to heat-sensitive group, and those
      with occurrence of heat-sensitivity being equal to or less than 2 times assigned
      to non-sensitive moxibustion group. According to Portmann Scale (including
      movement and resting posture) for the voluntary movement state of the face,
      forehead, winkles eye closure, open mouth smile, snarl, and pucker; points 0, 1,
      2 and 3 indicate no muscular movement, marked asynersis, asynersis and normal,
      respectively. In the light of resting posture of the eye, the nasolabial fold and
      mouth corner, 0, 1, and 2 points indicate severe, mild dissymmetry and normal,
      separately. In evaluation of the therapeutic effect, twenty points (at most)
      indicate cured, 17-19 points marked improvement; 14- 16 points improved, and < or
      = 13 points failure. RESULTS: Compared with pre-treatment, Portmann scores of
      both heat-sensitive moxibustion and non-sensitive moxibustion groups were
      significantly increased after the treatment (P < 0.001), and the score of the
      heat-sensitive moxibustion group was markedly higher than that of the non
      sensitive moxibustion group (P < 0.05). Of the 21 and 22 facial palsy patients in
      the heat-sensitive moxibustion and non-sensitive moxibustion groups, 8 and 5
      cases were cured, 10 and 7 were markedly effective, 3 and 10 were improved, with
      the markedly effective rates being 85.71% and 54.55%, respectively. The
      therapeutic effect of the heat-sensitive moxibustion group was statistically
      better (P < 0.05). CONCLUSION: Heat-sensitive moxibustion is significantly
      superior to non-sensitive moxibustion in improving symptoms of peripheral facial
      palsy patients, suggesting a necessity for paying attention to patients'
      reactions during moxibustion treatment.

PMID- 24579366
TI  - [Observation on clinical effects of moxibustion stimulation of different
      sensitive status acupoints for knee osteoarthritis].
AB  - OBJECTIVE: To observe the clinical effect of moxibustion of different acupoints
      undergoing heat-sensitive state and resting state in the treatment of knee
      osteoarthritis (KOA) patients. METHODS: A total of 60 cases of KOA patients were
      enrolled in the present trial. They were divided into heat-sensitive moxibustion
      (heat-sensitive) group and non-sensitive moxibustion group (resting group).
      Moxibustion was applied to Neixiyan (EX-LE 4), Waixiyan (i.e. Dubi, ST 35) and
      Heding (EX-LE 2) for about 45 min, once daily for 20 days. The heat-sensitive
      state was evaluated according to the patient's feeling. After moxibustion
      stimulation at the acupoint area, if the patient feels the heat penetrating from
      the skin surface to the deep tissue, or/and extending peripherally around the
      moxibustion site, or/and transmitting toward a certain direction, it is
      considered to be heat sensitization state. The therapeutic effect was evaluated
      by using visual analogue scale (VAS) for pain severity changes and by Guiding
      Principles for Clinical Trials of New Drugs of Chinese Materia Medica for
      evaluating functional activity of the knee-joint. RESULTS: After 20 sessions of
      treatment and after a half year's follow-up, the total integrated scores of VAS
      in the heat-sensitive group were all lower than those of the resting group (P <
      0.01). Following 20 sessions of treatment, of the two 30 KOA patients in the heat
      sensitive group and resting group, 14 (46.67% )and 5 (16.67%) experienced a
      marked improvement, 10 (33.33%) and 9 (30.00%) were effective, 6 (20.00%) and 16
      (53.33%) were invalid, with the effective rates being 80.00% and 46.67 ,
      respectively. Half-year's follow-up showed that the effective rates of the heat
      sensitive group and resting group were 79.17% (19/24) and 42.86% (6/14),
      respectively, suggesting a better therapeutic effect of heat-sensitive
      moxibustion. CONCLUSION: The clinicaln effect of heat-sensitive moxibustion is
      significantly superior to that of non-sensitive moxibustion in the treatment of
      KOA patients, being worthy of clinical application.

PMID- 24579367
TI  - [Analysis on Qijie (pathway of qi) theory of acupuncturology].
AB  - In order to clarify the connotation and academic significance of the term Qijie
      (pathway of qi) in Chinese medicine, the author of the present article collected
      related ancient literature and made a theoretical analysis on its concept, its
      relevance to the content of Sihai (four seas i.e.: 1) the brain, the sea of
      marrow, 2) Danzhong, the sea of qi; 3) stomach: the sea of water and food; 4)
      Chongmai, the sea of the 12 meridians), its related application and the evolution
      of the relationship between acupoints and their subordinated meridian. The author
      holds that the four Qijie aims at explaining the underlying mechanism of
      acupoints located on the head, chest and abdominal regions. The four Qijie theory
      was established in the transition period of the developmental process of meridian
      acupoint theory, and is of realistic significance in elucidating the correlation
      between the back shu-acupoints and zang-fu organs.

PMID- 24579368
TI  - [Significance of molecular network regulation of microRNA for studies on
      mechanisms of acu-moxibustion therapy].
AB  - Bioinformatics analysis of the molecular network regulation is the main content
      of systems biology, may reveal the complex life phenomena from interactions among
      molecules and will bring about a far-reaching impact on our current understanding
      about life activities of organism. MicroRNAs (functional RNAs) can regulate mRNA
      transcription through inhibition of post-transcriptional protein-coding gene
      expression, target degradation, etc., and are extensively involved in various
      biological processes in the cells. It is generally held that the therapeutic
      effect of acu-moxibustion intervention involves multi-channels, multi-targets,
      and multi-levels of both peripheral and central nervous systems of the body but
      has not been fully revealed, being similar with functional forms of molecular
      regulatory networks. Thus, it is necessary to introduce new ideas and methods for
      studying the underlying mechanism of acu-moxibustion therapy. The molecular
      regulatory networks of microRNA would provide a new way for revealing the
      mechanism of acu-moxibustion interventions.

PMID- 24579369
TI  - [Progress of researches and comments on promoters initiating effects of
      acupuncture stimulation of acupoints].
AB  - Acupoints, the local initial site of signals of acupuncture or moxibustion
      stimulation, play an important role in producing clinical therapeutic effects.
      The whole process of acupuncture stimulation induced improvement of the related
      visceral dysfunction or regional disorders includes 3 key links: 1) initiation of
      acupuncture/moxibustion signals from the stimulated acupoints; 2) conduction,
      coordination and integration of the complicated peripheral and central networks;
      and 3) responses of the target organs. Abundant research results indicate that
      acupuncture or moxibustion stimulation can induce specific changes in the
      regional micro-environment such as excitement of the peripheral cells, release of
      chemical substances, excitement of the afferent nerve, etc., which constitutes
      the important biological basis of the initial process of regional acupoint
      signals for producing therapeutic effects.

PMID- 24579370
TI  - Polymeric nanoparticle formulation of octapeptide (NP-OP): in vitro release and
      in vivo effect in common marmosets, Callithrix jacchus Linn.
AB  - Octapeptide (OP)/FSH-Receptor Binding Inhibitor-8 (FRBI-8), is a synthetic
      peptide corresponding to N-terminal sequence of purified fraction of Follicle
      Stimulating Hormone Binding-Inhibitor (FSHBI), isolated earlier from human
      ovarian follicular-fluid. In order to avoid the repeated drug-administration, OP
      loaded, polymeric polylactide (PLA) nanoparticle formulation (NP-OP), was
      developed using multiple-emulsion technique. This yielded an average particle
      size of 120 nm with 70% encapsulation-efficiency. In vitro release profile of NP
      OP showed sustained release of OP for 21 days. In vivo anti-fertility studies
      were conducted in marmosets. Results indicated that control animals conceived in
      the same cycle while two of three treated animals failed to conceive in treatment
      cycle. The in vivo studies thus corroborate with in vitro release of OP,
      demonstrating its anti-fertility activity in 66% of animals.

PMID- 24579371
TI  - Isolation, characterization and antigenic cross-reactivities of the major
      hemorrhagin from Cryptelytrops purpureomaculatus venom.
AB  - The major hemorrhagin from C. purpureomaculatus (mangrove pit viper) venom was
      purified to homogeneity and termed Maculatoxin. Maculatoxin has a molecular
      weight of 38 kDa as determined by SDS-PAGE. It is an acidic protein (pI= 4.2) and
      exhibited proteolytic and hemorrhagic activities (MHD10 = 0.84 microg in mice)
      but was not lethal to mice at a dose of 1 microg/g. The hemorrhagic activity of
      Maculatoxin was completely inactivated by EDTA and partially inhibited by ATP and
      citrate. The N-terminal sequence of Maculatoxin (TPEQQRFPPTYIDLGIFVDHGMYAT)
      shares a significant degree of homology with the metalloprotease domain of other
      venom hemorrhagins. Indirect ELISA showed anti-Maculatoxin cross reacted with
      protein components of many snake venoms. In the double-sandwich ELISA, however,
      anti-Maculatoxin cross-reacted only with venoms of certain species of the
      Trimeresurus (Asia lance-head viper) complex, and the results support the recent
      proposed taxonomy changes concerning the Trimeresurus complex.

PMID- 24579372
TI  - Housing under the pyramid reduces susceptibility of hippocampal CA3 pyramidal
      neurons to prenatal stress in the developing rat offspring.
AB  - Mother-offspring interaction begins before birth. The foetus is particularly
      vulnerable to environmental insults and stress. The body responds by releasing
      excess of the stress hormone cortisol, which acts on glucocorticoid receptors.
      Hippocampus in the brain is rich in glucocorticoid receptors and therefore
      susceptible to stress. The stress effects are reduced when the animals are placed
      under a model wooden pyramid. The present study was to first explore the effects
      of prenatal restraint-stress on the plasma corticosterone levels and the
      dendritic arborisation of CA3 pyramidal neurons in the hippocampus of the
      offspring. Further, to test whether the pyramid environment would alter these
      effects, as housing under a pyramid is known to reduce the stress effects,
      pregnant Sprague Dawley rats were restrained for 9 h per day from gestation day 7
      until parturition in a wire-mesh restrainer. Plasma corticosterone levels were
      found to be significantly increased. In addition, there was a significant
      reduction in the apical and the basal total dendritic branching points and
      intersections of the CA3 hippocampal pyramidal neurons. The results thus suggest
      that, housing in the pyramid dramatically reduces prenatal stress effects in
      rats.

PMID- 24579373
TI  - Specific absorption rate variation in a brain phantom due to exposure by a 3G
      mobile phone: problems in dosimetry.
AB  - A specific absorption rate (SAR) measurements system has been developed for
      compliance testing of personal mobile phone in a brain phantom material contained
      in a Perspex box. The volume of the box has been chosen corresponding to the
      volume of a small rat and illuminated by a 3G mobile phone frequency (1718.5
      MHz), and the emitted radiation directed toward brain phantom .The induced fields
      in the phantom material are measured. Set up to lift the plane carrying the
      mobile phone is run by a pulley whose motion is controlled by a stepper motor.
      The platform is made to move at a pre-determined rate of 2 degrees per min
      limited up to 20 degrees. The measured data for induced fields in various
      locations are used to compute corresponding SAR values and inter comparison
      obtained. These data are also compared with those when the mobile phone is placed
      horizontally with respect to the position of the animal. The SAR data is also
      experimentally obtained by measuring a rise in temperature due to this mobile
      exposures and data compared with those obtained in the previous set. To seek a
      comparison with the safety criteria same set of measurements are performed in 10
      g phantom material contained in a cubical box. These results are higher than
      those obtained with the knowledge of induced field measurements. It is concluded
      that SAR values are sensitive to the angular position of the moving platform and
      are well below the safety criteria prescribed for human exposure. The data are
      suggestive of having a fresh look to understand the mode of electromagnetic field
      -bio interaction.

PMID- 24579374
TI  - Neurobiological effect of 7-nitroindazole, a neuronal nitric oxide synthase
      inhibitor, in experimental paradigm of Alzheimer's disease.
AB  - Nitric oxide plays a role in a series of neurobiological functions, underlying
      behaviour and memory. The functional role of nNOS derived nitric oxide in
      cognitive functions is elusive. The present study was designed to investigate the
      effect of specific neuronal nitric oxide synthase inhibitor, 7-nitroindazole,
      against intracerebroventricular streptozotocin-induced cognitive impairment in
      rats. Learning and memory behaviour was assessed using Morris water maze and
      elevated plus maze. 7-nitroindazole (25 mg/kg, ip) was administered as
      prophylactically (30 min before intracerebroventricular streptozotocin injection
      on day 1) and therapeutically (30 min before the assessment of memory by Morris
      water maze on day 15). Intracerebroventricular streptozotocin produced
      significant cognitive deficits coupled with alterations in biochemical
      indices.These behavioural and biochemical changes were significantly prevented by
      prophylactic treatment of 7-nitroindazole. However, therapeutic intervention of 7
      nitroindazole did not show any significant reversal. The results suggests that 7
      nitroindazole can be effective in the protection of dementiainduced by
      intracerebroventricular streptozotocin only when given prophylactically but not
      therapeutically.

PMID- 24579375
TI  - Learning and memory promoting effects of crude garlic extract.
AB  - Chronic administration of aged garlic extract has been shown to prevent memory
      impairment in mice. Acute and chronic (21 days) effects of marketed formulation
      of crude garlic extract (Lasuna) were evaluated on learning and memory in mice
      using step down latency (SDL) by passive avoidance response and transfer latency
      (TL) using elevated plus maze. Scopolamine (0.4 mg/kg, ip) was used to induce
      amnesia in mice and piracetam (200 mg/kg, ip) served as positive control. In the
      acute study, Lasuna (65 mg/kg, po) partially reversed the scopolamine-induced
      amnesia but failed to improve learning and memory in untreated animals. Chronic
      administration of Lasuna (40 mg/kg/day for 21 days) significantly improved
      learning both in control and scopolamine induced amnesic animals. Influence of
      Lasuna on central cholinergic activity and its antioxidant properties were also
      studied by estimating the cortical acetylcholinesterase (AchE) activity and
      reduced glutathione (GSH) levels respectively. Chronic administration of Lasuna
      inhibited AchE, while increasing GSH levels. Thus the results indicate that long
      term administration of crude garlic extract may improve learning and memory in
      mice while the underlying mechanism of action may be attributed to the anti-AchE
      activity and anti-oxidant property of garlic.

PMID- 24579376
TI  - Anti-diabetic effect of a combination of andrographolide-enriched extract of
      Andrographis paniculata (Burm f.) Nees and asiaticoside-enriched extract of
      Centella asiatica L. in high fructose-fat fed rats.
AB  - Traditionally, a combination of medicinal plants is commonly used for lowering
      blood glucose in diabetic patients in order to provide additional benefits of the
      single drug. A. paniculata and C. asiatica are two traditional medicines form
      South Asian and Southeast Asain countries consumed by people for treating
      daibates mellitus and its complications. Hyperglycemia in the rats was stimulated
      by high fructose-fat diet that consists of 36% fructose, 15% lard, and 5% egg
      yolks in 0.36 g/200 g body weight for 70 days. The rats were orally administered
      with the combination of andrographolide-enriched extract of A. paniculata (AEEAP)
      leaves and asiaticoside-enriched extract of C. asiatica (AEECA) herbs from day 70
      for 7 days. Antidiabetic activity was evaluated by estimating mainly the blood
      glucose levels and other parameters such as HDL, LDL, cholesterol and
      triglyceride. The results showed that combination at the ratio of 70:30 exhibited
      a promosing antidiabetic effect in high-fat-fructose-fed rat, and exhibited
      sinergistic effects on blood cholesterol and HDL levels. It can be concluded that
      its antidiabetic effect was better than that of single treatment of AEEAP or
      AEECA. That combination was also potential to develop as a blood glucose-lowering
      agent for diabetic patients.

PMID- 24579377
TI  - Protective effect of secondary plant metabolites from Ipomoea aquatica Forsk.
      against carbofuran induced damages.
AB  - Plausible interactions between food contaminants and natural constituents in vivo
      and protective effect of polyphenols present in I. aquatica against carbofuran
      toxicity in Charles Foster rats were evaluated. Determinations based on
      antioxidant enzyme activities showed significant alterations in glutathione,
      glutathione peroxidase, superoxide dismutase and catalase in tissues (liver and
      brain) and plasma of pesticide treated group while polyphenolic extracts from I.
      aquatica (IAE) attenuated their activities when given alongwith carbofuran. IAE
      decreased enhanced lipid peroxidation levels in plasma and erythrocyte membrane
      and cholesterol levels in brain and plasma. IAE also minimized histopathological
      degenerative changes produced by carbofuran. While single cell gel
      electrophoresis showed that secondary metabolites in leafy vegetables produced a
      combinatorial effect with pesticide at cellular level, DNA fragmentation level in
      bone marrow cells showed a decline in the IAE treated rats. Food safety adversely
      affected by various chemical contaminants can be retained by plant polyphenols
      and secondary plant constituents that can be found together in bolus. Therefore,
      the present study gives an insight into the protective role of naturally found
      polyphenols against pesticide toxicity.

PMID- 24579378
TI  - A novel combination of plant growth regulators for in vitro regeneration of
      complete plantlets of guar [Cyamopsis tetragonoloba (L.) Taub].
AB  - A novel combination of plant growth regulators comprising indole-3-butyric acid
      (IBA), 6-benzylaminopurine (BA) and gibberellic acid (GA3) in Murashige and Skoog
      basal medium has been formulated for in vitro induction of both shoot and root in
      one culture using cotyledonary node explants of guar, (Cyamopsis tetragonoloba).
      Highest percentages of shoot (92%) and root (80%) induction were obtained in the
      medium containing (mg/L) 2 IBA, 3 BA and 1 GA3. Shoot regeneration from the
      cotyledonary node explants was observed after 10-15 days. Regeneration of roots
      from these shoots occurred after 20 to 25 days. The regenerated plantlets showed
      successful acclimatization on transfer to soil. This protocol is expected to be
      helpful in carrying out various in vitro manipulations in this economically and
      industrially important legume.

PMID- 24579379
TI  - Deployment of gene specific marker in development of kunitz trypsin inhibitor
      free soybean genotypes.
AB  - Genetic elimination of kunitz trypsin inhibitor in soybean seed would obviate the
      need for boiling required to inactivate the antinutritional factor and therefore
      economize the soy processing. PI542044, the source of null variant of kunitz
      trypsin inhibitor gene is being used in the development of kunitz trypsin
      inhibitor free soybean genotypes in India. Gene specific marker can expedite the
      genetic elimination of this undesirable trait from popular soybean genotypes. In
      the present study, we tested the DNA amplification of soybean genotype PI542044
      and kunitz trypsin inhibitor null lines derived from this genotype with a gene
      specific primer developed from the null variant of PI157740. The amplicons so
      obtained corresponded to the absence of kunitz trypsin inhibitor protein band on
      10% polyacrylamide gel. The gene specific marker also amplified the null allele
      of template DNA of F1, BC1F1 and BC2F1 plants developed during marker assisted
      introgression of null allele of kunitz trypsin inhibitor into elite soybean
      cultivar JS97-52. The results presented show the utility of this gene specific
      marker developed from null allele of kunitz trypsin inhibitor for identification
      of kunitz trypsin inhibitor free genotypes developed from PI542044, the only
      source of null variant available in India.

PMID- 24579381
TI  - Experimental determination of the physicochemical properties of lumefantrine.
AB  - BACKGROUND: The physicochemical properties of lumefantrine, a first line
      combination medicine for the treatment of uncomplicated falciparum malaria have
      been determined experimentally rather than theoretically as a guide to
      understanding its disposition in human. METHOD: The solubility of lumefantrine in
      various organic solvents was evaluated by estimating the volume of solvent that
      completely dissolved 15 mg of the drug. Melting point determination was carried
      out using a melting point apparatus. Dissociation constant of the drug was
      determined potentiometrically in 0.1M perchloric acid and partition coefficient
      was by the method of Leo Hansch, using ratio of the concentration of organic to
      aqueous phase. RESULT: Lumefantrine has a melting point of 128-131 degrees C. Its
      solubility in selected solvents range from 0.013% in acetonitrile (very slightly
      soluble) to 7.5% in chloroform and dichloromethane (soluble), and it is
      practically insoluble (0.002%) in water. The ionization constant (pKa),
      determined in 0.1 M perchloric acid was found to be 9.35. The Log P lies in the
      range 2.29-3.52, confirming the lipophilicity of lumefantrine. CONCLUSION: The
      physicochemical properties of lumefantrine reveal that it is highly lipophilic,
      weakly basic and readily dissolves in non-polar and/or aprotic organic solvents.
      While these properties will favour its distribution across cellular membranes,
      the rate-limiting step will be at the dissolution-absorption stage which will
      require biopharmaceutical modifications.

PMID- 24579380
TI  - Molecular cloning and mRNA expression profile of sucrose transporter gene BnSUT1C
      from Brassica napus L.
AB  - The genomic and cDNA sequences of BnSUT1C were isolated from B. napus.
      Combination of cDNA and genomic DNA sequences revealed that the BnSUT1C gene
      contained three exons and two introns. The cDNA encodes a protein of 513 amino
      acids with a calculated molecular mass of 54.7 kDa and an isoelectric point of
      9.12. It exhibits typical features of sucrose transporter with 12 trans-membranes
      spanning domains. BnSUT1C showed highly homologous with AtSUC1 and AtSUC5. A
      histidine residue, which is conserved across all functional sucrose transporter
      proteins in higher plants, is located at position 66 of the BnSUT1C. Two putative
      pollen-specific cis-elements, AGAAA and GTGA motifs, are located in 5'-upstream
      of BnSUT1C. The spatial and temporal expression patterns carried out by semi
      quantitative RT-PCR and Real-Time PCR, which indicated that BnSUT1C predominantly
      expressed in later developmental stages of anther, as tapetal cells began to
      shrink and collapse. BnSUT1C could mediate the uptake of sucrose in the pollen
      and retrieval of tapetal degenerated products during pollen maturation.

PMID- 24579383
TI  - Anti-inflammatory and analgesic activity of a cucurbitacin isolated from
      Lagenaria breviflora Roberty fruit.
AB  - BACKGROUND: In this study, the bioactive compound in Lagenaria breviflora Roberty
      responsible for its anti-inflammatory and analgesic activities was isolated and
      chemically characterized. METHOD: Compounds in the whole fruit, bark, pulp and
      seed of L. breviflora were partitioned utilizing their various polarity in n
      hexane, ethyl acetate, chloroform and ethanol. The fractions of the extract
      obtained were tested for their bioactivities. The fraction with the most
      consistent anti-inflammatory and analgesic activities was further purified using
      accelerated gradient chromatography (AGC) and open column chromatography. Elution
      of compounds in this fraction was monitored through the different chromatography
      methods using thin layer chromatography (TLC). The pure compound isolated from
      the chromatography methods was taken for chemical characterization and
      elucidation of the structure. RESULTS: Ethyl acetate fraction of the whole fruit
      exhibited the most consistent anti-inflammatory and analgesic activities out of
      the 16 fractions obtained. Purification of this fraction with AGC yielded 7
      subfractions composing of eluents with similar Rf values on the TLC plate. One of
      the sub-fractions yielded a compound which was further purified using the open
      column chromatography method. Eluent obtained from this sub-fraction was renamed
      YO1. CONCLUSION: From the result of mass spectroscopy and nuclear magnetic
      resonance spectroscopy of the compound, the structure of YO1 was determined as a
      cucurbitacin with 10a-cucurbit-5-ene skeleton (9a-methyl-19-norlanosta 5-ene)
      backbone structure, with six carbon atoms attached to double bonds and one
      hydroxyl group.

PMID- 24579382
TI  - Validation of the oral impact on daily performance frequency scale in Ibadan,
      Nigeria.
AB  - BACKGROUND: Oral health related quality of life measures provide alternative ways
      to evaluate oral health status in a way that prioritises impact on lifestyle.
      These measures are, however, hardly used in our setting. Before the measures can
      be used effectively, validity of the tool needs to be evaluated. The aim of the
      study was to validate the Oral Impact on Daily Performance (OIDP) frequency scale
      in an adult Nigerian patient population. METHODOLOGY: This was a descriptive
      cross sectional study in which consecutive patients attending the Primary Oral
      Health Care Centre, Idikan and the Oral Diagnosis Clinic of the University
      College Hospital, Ibadan were recruited. Data was collected with OIDP structured
      interviewer administered questionnaires, global self-rating and perceived
      treatment need questions and by oral examination. The frequency scale of the OIDP
      index was used to compute the impact scores. Data collected was subjected to
      statistical analysis using SPSS version 19. RESULTS: A total of 204 patients
      participated in the study. The OIDP score ranged from 0 to 40; 78.9% of the
      participants reported an impact on daily performance with eating and enjoying
      food being the most reported activity impacted upon. The Cronbach's alpha
      coefficient was 0.811; the OIDP index was significantly associated with global
      self-ratings of oral health, perceived need for dental treatment and was able to
      discriminate between patients with or without dental caries. CONCLUSION: The OIDP
      frequency scale exhibited satisfactory psychometric properties amongst adult
      dental patients in Ibadan, Nigeria.

PMID- 24579384
TI  - An investigation of the prevalence of iron overload in Nigerian women.
AB  - BACKGROUND: Iron overload has been recognized to be a risk factor for numerous
      acute and chronic illnesses. It is generally assumed to be rare and
      acknowledgment of iron toxicity is difficult for some nutritional scientists,
      clinicians and laypersons. There is also a heightened interest to raise body iron
      through universal iron "fortified" foods. OBJECTIVE: This study investigated the
      need to examine the policy of unselective iron supplementation in a sub-Saharan
      African community. METHODS: This is a descriptive study carried out on 98
      apparently healthy women attending a Papanicolaou (PAP) smear clinic for routine
      cervical cancer screening. Information on demographic data and diet were obtained
      with structured questionnaires and serum samples were analyzed for serum iron
      (SI) and total iron binding capacity (TIBC) which were used to derive the values
      for tranferrin saturation (TS%). Iron overload was defined by tranferrin
      saturation greater than 50%. RESULTS: The prevalence of iron overload was 8.2% in
      women aged 26-71 years. Skilled workers constituted 44.9% of the population while
      semi-skilled and housewives were 50% and 5.1% respectively. Eighty four percent
      of the women had been on iron vitamin supplement at one time or the other. Mild
      anaemia was present in 25% of the women with iron overload. The prevalence of
      iron overload between women who were actively reproducing and those who were not
      was not statistically different. CONCLUSIONS: Iron overload is common, therefore,
      iron studies may be included in routine investigation and selective iron
      supplementation should be encouraged. Moreso, iron loading anaemia should be
      ruled out in patients with anaemia before prescribing iron therapy.

PMID- 24579385
TI  - Renal cell carcinoma in Ibadan: a 5-year clinicopathologic review.
AB  - BACKGROUND: To review all the cases of the patients with renal cell carcinoma
      seen during the study period and to determine the pattern of presentation, number
      of operable cases, histological types and outcome of treatment. MATERIALS AND
      METHODS: The data of the patients with renal cell carcinoma was retrieved from
      the Urology division audit book, theatre record books and case files from the
      health records department and pathology register in the department of pathology.
      The parameters studied were age, gender, pattern of presentation, number of
      patients who had surgery, histology types and the outcome of treatment. RESULTS:
      In total, there were 69 patients with renal cell carcinoma that accounted for
      59.5% of all renal masses seen. The male to female ratio was 1:1. Their age
      ranged from 16 to 88 with a mean of 48 years and median of 50 years. The main
      clinical feature was loin swelling (100%) and others were loin pain (29%),
      hematuria (18.8%), weight loss (4%) and paraneoplastic syndrome (anaemia without
      haematuria) was seen in 2.9%. Ten percent of the cases had the classical triad of
      hematuria, loin pain and loin swelling. All cases were unilateral disease and 15
      (21.7%) had metastasis at presentation. The pre-operative tests were abdominal
      ultrasound (94%), intravenous urography (45%) and CT-Scan (11.6%). Twenty eight
      patients (40.6%) had surgery of which 5 were unresectable. 37 of the patients
      (53.6%) were subsequently lost to follow-up. The 28 operative specimens were
      histologically confirmed and 85.7% were clear cell carcinoma. The 23 patients
      whose tumours were resected have remained symptom free, some up to 5 years.
      However the five patients with unresectable tumours died between 3 to 6 months of
      exploratory surgery. CONCLUSION: The patients with resectable tumour could remain
      disease free for a significant period afterwards despite late presentation.
      However, there is a high loss to follow-up rate.

PMID- 24579386
TI  - Stroke lesions and post-stroke depression among survivors in Ibadan, Nigeria.
AB  - BACKGROUND: We aimed to determine the association between the neuro-radiological
      characteristics of stroke lesions and post-stroke major depression among
      survivors in Ibadan, Nigeria. This is in the background of a paucity of
      information on the clinico-pathological correlation of post-stroke emotional
      responses among African Survivors. METHOD: We studied 30 stroke survivors
      receiving physiotherapy. The radiological characteristics of the stroke lesions
      were documented using computerized tomography or magnetic resonance imaging scans
      in the acute phase of the stroke. While the presence of major depressive disorder
      meeting criteria in the fourth edition of the Diagnostic and Statistical Manual
      was assessed using the Schedule for Clinical Assessment in Neuropsychiatry
      (SCAN), between 3 months and 2 years after. The association between lesion
      characteristics and depression was explored using logistic regression analysis.
      RESULT: Nine (30.0%) stroke survivors met criteria for major depressive disorder.
      There were significant differences in their gender. The differences in the lesion
      types approached the set level of significance in survivors with or without major
      depressive disorder. There were however no differences when considering
      hemispheric lateralization or intra-hemispheric lesion location. Being female,
      but not the lesion characteristics was strongly associated with post-stroke major
      depressive disorder CONCLUSION: Lesion characteristics documented in the acute
      phase of stroke could not predict the occurrence of major depressive disorder
      during rehabilitation in this sample. The occurrence of depression among stroke
      survivors may ultimately be determined by a combination of factors.

PMID- 24579387
TI  - Patients' knowledge and exercise of their rights at the University College
      Hospital, Ibadan.
AB  - BACKGROUND: Patient rights have recently become the centre of national attention
      in the healthcare practice and Nigerians are becoming more aware of their rights.
      Despite this awareness, there is gap between their knowledge and ability to
      exercise their rights. The study was designed to assess University College
      Hospital patients' knowledge and exercise of their rights. METHOD: This
      descriptive, cross-sectional study utilized a 45-item and self-administered
      questionnaire to gather information from three hundred and sixty (360) patients.
      The sample size was statistically determined and the respondents were randomly
      selected from Out-Patient Department. Ethical issues were duly considered. Data
      collection spanned four weeks. Data were analysed through the use of Statistical
      Package for Social Sciences (SPSS) version17. RESULTS: Most of the respondents
      (94.2%) have good knowledge of rights and few (37.2%) of them denied being
      actively involved in making decisions on issues concerning their care. However,
      about half (50.8%) claimed they were not fully informed about the diagnosis and
      treatment plans regarding their health conditions. About 75.0% of the respondents
      reported that they would seek redress if their rights are infringed upon.
      CONCLUSION: Patients have good knowledge of their rights, yet they are not fully
      exercising these rights. Patients should be encouraged to participate in the
      decision making process on their health issues because it is a channel towards
      achieving positive patient outcomes. Adequate information about care including
      the risks of procedures, cost implications of care and possible outcomes of care
      among others should be provided. Provision of more information by health care
      providers may enhance patients' decision making and exercise of rights.

PMID- 24579388
TI  - Beta thalassaemia in Nigeria: myth or fact?
AB  - BACKGROUND: The high prevalence of sickle cell disorders and the mild deletional
      a-thalassaemia among Nigerians is well known, but a-thalassaemia is believed to
      be almost nonexistent. Beta thalassaemia trait (BTT) was screened for in patients
      with unexplained recurrent haemolytic anaemia and healthy individuals. METHODS: a
      thalassaemia trait (BTT) was screened for using MCH and HbA2 of 27 pg and 3.5%
      respectively as cut off in 151 Nigerians which included 29 patients and 122
      apparently healthy individuals. The subjects were categorized into four, Group I
      (high HbA2, low MCH), Group II (low HbA2 and MCH), Group III (high HbA2 and
      high/normal MCH) and Group IV (normal HbA2 and MCH). RESULTS: Group I are
      possible carriers of BTT while group IV are least likely to carry either alpha or
      beta thalassaemia genes. There were 36 (26%), 39 (28%), 27 (19%) and 38 (27%) in
      groups I-IV respectively. The mean MCH, MCV, haematocrit and HbA, for the study
      population were 26 +/- 2.8, 81 +/- 7.9, 37.5 +/- 6.8 and 3.4 +/- 1.7
      respectively. The mean MCV and haematocrit were significantly lower for group I
      compared to group IV (76.9 Vs. 86.6, p=0.00) and (36.5Vs39.7, p=0.03)
      respectively. Group II had significantly lower MCV and haematocrit than group IV
      (75.4 (p=0.00) and 36.4 (p=0.01) respectively. There was a positive correlation
      between the MCH and MCV with the haematocrit (p=0.004, p=0.001 respectively) but
      HbA2 showed a stronger negative correlation with the haematocrit (p<0.0001).
      CONCLUSION: This does not only show the presence of BTT, but a higher prevalence
      than previously thought, mutations responsible for it should therefore be
      characterized.

PMID- 24579389
TI  - Survival of glass fiber post retained endodontically treated teeth preliminary
      report.
AB  - BACKGROUND: The use of fiber reinforced composite post in restoration of
      endodontically treated teeth have been found to prevent irreparable root fracture
      and the fact that the post is bonded to the root giving a monobloc restoration,
      also strengthens the tooth. This preliminary study aimed to evaluate the survival
      of endodontically treated teeth with compromised coronal tooth structure restored
      with glass-fiber posts after 6 months. METHODOLOGY: Twenty endodontically treated
      teeth with less than 50% coronal tooth structure, were assessed and restored with
      glass fiber reinforced post cemented with dual cure composite and porcelain fused
      to metal crown. Patients were recalled and the teeth re-assessed at 3 and 6
      months to evaluate their survival. The criteria for success included post and
      core in situ with no displacement or detachment of the post, no crown or
      prosthesis decementation, no post, core, or root fracture and absence of
      periradicular conditions requiring endodontic retreatment. RESULT: Eighteen teeth
      were available for review at both 3rd and 6th months out of which none had post
      core-crown fracture. One tooth (5%) had minimal crevice on probing the margin at
      6 month's review, while another tooth had < or =1 mm mobility of the crown during
      the same review period. CONCLUSION: Within the limitation of the study, there was
      an excellent performance of the teeth restored with glass fiber post with respect
      to post -core- crown and root fracture at the end of the 6months recall visit.

PMID- 24579390
TI  - Metachronus endometrial carcinoma in a seventy five year old woman with carcinoma
      of the left breast treated with tamoxifen.
AB  - BACKGROUND: A second cancer is a different type of cancer than the original
      cancer. It is diagnosed after a completed treatment for the first cancer. Second
      cancers occur in only one to three percent of survivors. The level of risk is
      very small. In general, greater numbers of cancer survivors are living longer due
      to improvements in treatment. Whether or not a second cancer develops is
      dependent on many factors. These include the age of the patient when treated, the
      treatment received, the genetic make-up and family history. The actual number of
      people who will get a second cancer is relatively small. Each cancer survivor's
      experience is unique. The aim of this report is to call attention to what might
      be an emerging place of secondary malignancies in cancer survivors in our
      setting. METHOD: We report a case seen in our practice of a seventy five year old
      woman who was treated for invasive ductal carcinoma of the left breast and
      developed invasive endometrial carcinoma about 4 years later. CONCLUSION: There
      is a need to be on the lookout for possible second malignancies in cancer
      survivors. Examination and tests for second malignancies should be part of the
      routine follow up procedures in this group of patients.

PMID- 24579391
TI  - Adulthood hirschprung's disease: a report of 4 cases in Ile-Ife. Nigeria.
AB  - BACKGROUND: Hirschsprung's disease in adulthood is very rare and is often
      misdiagnosed. We present four cases of adulthood Hirschsprung's disease seen in
      the last two decades to illustrate challenges accompanying its diagnosis and
      management. METHOD: This descriptive case series included cases of histologically
      proven Hirschsprung's seen in adulthood at the Obafemi Awolowo University
      Teaching Hospitals Complex in the last two decades (1991-2011). The clinical
      data, radiological investigations, details of surgical treatment, histological
      diagnosis, outcomes and complications were analyzed. RESULT: There were 4 adult
      patients, 3 males and 1 female with age ranging from 17 to 74 years (mean 23
      years). Each patient presented with sub acute intestinal obstruction needing two
      staged procedures of initial colostomy followed by definitive procedure of low
      anterior resection (State procedure) in 3 patients and Swenson-Bill procedure in
      one. There was one mortality and good long term outcome in the remaining three.
      CONCLUSION: This review presented the oldest patient presenting with adult
      Hirschsprung's and the highest mean age of any case series. Four patients with
      adulthood Hirschsprung's disease managed by two operative procedures enabled
      comparison of operative outcome with respect to complications and functional
      outcomes. Mortality seems to correlate with presentation at old age, which is
      usually due to life long self-management of chronic constipation. Though very
      rare, a high index of suspicion of adulthood Hirschprung's disease should be
      maintained in adult patients with recurrent chronic constipation needing lifelong
      laxative, enema or mechanical wash-out.

PMID- 24579392
TI  - Cutaneous metastasis from prostate cancer in a nigerian: a case report and
      literature review.
AB  - BACKGROUND: Prostate cancer is the most common male malignancy in Nigeria and
      most patients present with advanced and metastatic disease. Cutaneous metastasis
      from prostate cancer is rare worldwide and to our knowledge has not been
      previously reported in a native African. We hereby report a case in a 62-year-old
      Nigerian. CASE PRESENTATION AND MANAGEMENT: A 62-yr-old Nigeria man presented
      with 6 months history of lower urinary tract symptoms that culminated in urinary
      retention for which he was catheterized. He noticed multiple painless skin
      nodules about the same time on the neck and trunk. On examination, he had
      multiple cutaneous nodules on his neck, limbs and trunk. His prostate gland was
      enlarged, hard and irregular. Prostate biopsy revealed adenocarcinoma of the
      prostate. He had bilateral orchidectomy with progressive regression of the skin
      nodules. He had successful trial of voiding without a catheter 3 weeks after
      bilateral total orchidectomy. CONCLUSION: Cutaneous metastasis from prostate
      cancer is rare in native Africans despite the high incidence of the disease in
      this population. To our knowledge, this index case is the first report in a
      native African in the English literature.

PMID- 24579393
TI  - 2014--a time to care for ourselves?

PMID- 24579394
TI  - Take action: influence diversity.
AB  - Increased diversity brings strength to nursing and ANNA. Being a more diverse
      association will require all of us working together. There is an old proverb that
      says: "one hand cannot cover the sky; it takes many hands." ANNA needs every one
      of its members to be a part of the diversity initiative.

PMID- 24579395
TI  - Training patients for automated peritoneal dialysis: A survey of practices in six
      successful centers in the United States.
AB  - In the United States, the majority of patients on peritoneal dialysis (PD) use a
      cycler or automated peritoneal dialysis (APD). The aim of this study was the
      identification of common features in nurse-led APD training programs that were
      likely to contribute to successful home dialysis. This study collected data on
      nurse-led APD training programs in six high-performing PD centers. A 13-point
      survey, which focused on training tools, topics covered methods used, and level
      of support at home, was administered during group face-to-face interviews with
      the PD training nurses. Data were reviewed for trends between centers. Training
      programs in all six centers focused on essential information and skill sets to
      begin home dialysis using APD, with simple instructions and a hands-on approach.
      Every center initially trained patients on continuous ambulatory PD before APD.
      The clinics provided ongoing education, reinforcement, and retraining of concepts
      and skills through discussion, quizzes, and topic-specific monthly training
      sessions. All clinics provided 24-hour support for patients. Adopting the best
      practices identified in this study has the potential to improve APD training.

PMID- 24579397
TI  - Putting the 'C' back into continuous renal replacement therapy.
AB  - It may seem obvious that continuous renal replacement therapy (CRRT) means that
      the treatment is truly continuous--administered without interruption on a 24/7
      basis. In reality, a number of barriers limit the continuous aspect of CRRT. This
      article describes how nursing staff of an inpatient dialysis unit in a large
      Midwestern academic institution identified these barriers and developed and
      implemented a multifaceted plan to optimize CRRT.

PMID- 24579396
TI  - Development and cultural adaptation of the Spanish version of the End Stage Renal
      Disease Adherence Questionnaire (SESRD-AQ).
AB  - We previously developed and validated the End-Stage Renal Disease Adherence
      Questionnaire (ESRD-AQ) to measure adherence behaviors (e.g., hemodialysis
      attendance, medication use, fluid restrictions, and diet) of patients on
      maintenance hemodialysis. To determine whether the ESRD-AQ can be used to measure
      adherence behaviors in non-English-speaking patients, we translated and adapted
      the ESRD-AQ into Spanish (SESRD-AQ) using forward and backward translation and
      cultural adaptation of the content. Validity and reliability were measured using
      item-level content validity indexes, intraclass correlation coefficients, and
      known-group analysis. All validity indices were within an acceptable range;
      strong test-retest stability existed across all items, with intraclass
      correlation coefficients ranging from 0.82 to 1.00. The developed SESRD-AQ is a
      valid assessment tool for use among Spanish-speaking patients on maintenance
      hemodialysis. This instrument refinement and validation process can be replicated
      with other maintenance hemodialysis population groups.

PMID- 24579398
TI  - Symbolic representations of living with chronic kidney disease.
AB  - Visual or aesthetic data can contribute to understanding experiences that may not
      be able to be fully understood through spoken or written words. This article
      describes stories of symbols that represent the experiences of individuals living
      with chronic kidney disease. Symbols included both objects (i.e., a family
      photograph) and intangible representations (i.e., apiece of music) that were
      chosen because they innately held meaning to the person. Descriptive themes of
      the symbols included hopes and inspirations, reflections on "who I am," and
      confrontations of illness. Participants' expressions through symbols were further
      described through the use of stories of memories, emotions, and poetic devices.
      We contend that symbols convey aspects of experience that cannot easily be
      translated into oral expression.

PMID- 24579399
TI  - Physical function and gait speed in patients with chronic kidney disease.
AB  - Patients with chronic kidney disease (CKD) who are treated with dialysis have
      impaired physical functioning that is associated with poor outcomes. Gait speed
      is an important measure of mobility that predicts adverse events and mortality in
      older people. Gait speed is low in patients with CKD, and those treated with
      hemodialysis average below cut-points known to indicate increased risk of reduced
      survival and adverse health events. Measurement of gait speed in patients with
      CKD may be valuable in identifying those at risk for adverse events, including
      disability and mortality.

PMID- 24579401
TI  - Hemodialysis-related cramps and nocturnal leg cramps--what is best practice?

PMID- 24579400
TI  - Therapeutic plasma exchange in a patient with myasthenia gravis.
AB  - Tom was an interesting combination of a patient requiring both renal placement
      therapy and TPE. Because there are available through the inpatient dialysis unit,
      it provided an opportunity to educate Tom on apheresis treatments as well as
      treatment options for chronic disease. Discussion with Tom during these
      treatments revealed that he wanted to retain as much autonomy and responsibility
      for his care as possible. Collaboration with the nephrologists and neurologist,
      as well as the outpatient infusion center, allowed Tom to schedule treatments
      before he experienced a myasthenic crisis but also hospitalization, which could
      increase his risk of infection. The time he spent receiving the TPE treatments
      was a unique and wonderful opportunity to answer all of Tom's questions about
      treatment modalities and allowed nursing staff to advocate fully for his wishes.
      At the time of this writing, Tom has remained free of myasthenic symptoms and has
      not required TPE treatments for over two years.

PMID- 24579402
TI  - A personal taste of organizational reform.

PMID- 24579403
TI  - Is the NCHD changeover associated with increased risk of intravenous catheter
      related infections?

PMID- 24579404
TI  - 49th Doolin Lecture: AE (Freddy) Wood: the patient, the surgeon and the
      regulator: 7th Dec 2013.

PMID- 24579405
TI  - Towards realistic and flexible advance care planning.

PMID- 24579406
TI  - Cancer incidence and mortality due to alcohol: an analysis of 10-year data.
AB  - Alcohol consumption is causally related to cancer of the upper aero-digestive
      tract, liver, colon, rectum, female breast and pancreas. The dose response
      relationship varies for each site. We calculated Ireland's cancer incidence and
      mortality attributable to alcohol over a 10-year period. Between 2001 and 2010,
      4,585 (4.7%) male and 4,593 (4.2%) female invasive cancer diagnoses were
      attributable to alcohol. The greatest risk was for the upper aero-digestive tract
      where 2,961 (52.9%) of these cancers in males and 866 (35.2%) in females were
      attributable to alcohol. Between 2001 and 2010, 2,823 (6.7%) of male cancer
      deaths and 1,700 (4.6%) of female cancer deaths were attributable to alcohol.
      Every year approximately 900 new cancers and 500 cancer deaths are attributable
      to alcohol. Alcohol is a major cause of cancer after smoking, obesity and
      physical inactivity. Public awareness of risk must improve. Over half of alcohol
      related cancers are preventable by adhering to Department of Health alcohol
      consumption guidelines.

PMID- 24579407
TI  - Are Irish adult general practice consultation rates as low as official records
      suggest? A cross sectional study at six general practices.
AB  - Accurate data on primary care activity is key to health services planning and
      reconfiguration. Official data estimate general practice adult consultation rates
      to be 3.2 visits annually, based on patient self reports. We aim to estimate the
      consultation rate using practice based data and compare this to official
      estimates. We interrogated six general practices' information systems and
      estimated consultation rates based on practice, telephone, domiciliary and out of
      hours consultations by patients aged 18 years or older. The study population
      (20,706 patients) was representative of the national population in terms of age
      and GMS status. The mean consultation rate was 5.17, though this was higher among
      GMS-eligible patients and among older age groups. Estimates of consultation rates
      derived from practice based data are likely to be higher than that derived from
      other approaches. Using multiple sources of data will enhance accuracy of
      workload estimates and this will benefit service planning.

PMID- 24579408
TI  - Adverse event recording post hip fracture surgery.
AB  - Accurate recording of adverse events post hip fracture surgery is vital for
      planning and allocating resources. The purpose of this study was to compare
      adverse events recorded prospectively at point of care with adverse recorded by
      the Hospital In-Patient Enquiry (HIPE) System. The study examined a two month
      period from August to September 2011 at University Hospital Limerick. Out of a
      sample size of 39, there were 7 males (17.9%) and 32 females (82.1%) with an age
      range of between 53 and 98 years. The mean age was 80.5 years. 55 adverse events
      were recorded, in contrast to the HIPE record of 13 (23.6%) adverse events. The
      most common complications included constipation 10 (18.2%), anaemia 8 (14.5%),
      urinary retention 8 (14.50%), pneumonia 5 (9.1%) and delirium 5 (9.1%). Of the
      female cohort, 24 (68.8%) suffered an adverse event, while only 4 (57%) males
      suffered an adverse event.

PMID- 24579410
TI  - The compliance to acute asthma management protocols in paediatric emergency
      department.
AB  - Asthma guidelines should be followed closely to ensure improvement and
      consistency of outcome. In order to measure compliance with local acute asthma
      protocols, we reviewed notes of children presenting to our ED with acute asthma.
      We noted clinical assessment of severity of asthma exacerbation, compared
      management of cases with local protocols, noted time to first nebulisation,
      discharge advice and follow up plans. Retrospectively, 6 patients had life
      threatening, 70 had severe and 64 had mild-to-moderate exacerbation. We observed
      inconsistent documentation of clinical signs including, respiratory effort 6
      (100%), 62 (89%), 39 (61%), mental status 3 (50%), 46 (65%), 47 (73%) and speech
      1 (16.7%), 19 (27%), 7 (11%) in life threatening, severe and mild-to-moderate
      groups respectively. Bronchodilator therapy was delayed in life-threatening 3
      (50%) and severe cases 63 (90%). While discharge advice was documented in 54%
      patients, no written asthma action plans were given. This study demonstrated
      necessity of protocol-adherence in areas of clinical assessment, management and
      follow up.

PMID- 24579409
TI  - A national house-staff audit of medical prophylaxis in medical patients for the
      PREVENTion of Venous ThromboEmbolism (PREVENT-VTE).
AB  - We established a national audit to assess the thromboprophylaxis rate for venous
      thromoembolism (VTE) in at risk medical patients in acute hospitals in the
      Republic of Ireland and to determine whether the use of stickers to alert
      physicians regarding thromboprophylaxis would double the rate prophylaxis in a
      follow-up audit. 651 acute medical admission patients in the first audit and 524
      in the second re-audit were recruited. The mean age was 66.5 yrs with similar
      numbers of male and female patients and 265 (22.6%) patients were active smokers.
      The first and second audits identified 549 (84%) and 487 (93%) of patients at
      risk for VTE respectively. Of the at-risk patients, 163 (29.7%) and 132 (27.1%)
      received LMWH in the first and second audit respectively. Mechanical
      thromboprophylaxis was instigated in 75 (13.6%) patients in the first and 86
      (17.7%) patients in the second audit. The placement of stickers in patient charts
      didn't produce a significant increase in the number of at risk patients treated
      in the second audit. There is unacceptably low adherence to the ACCP guidelines
      in Ireland and more complex intervention than chart reminders are required to
      improve compliance.

PMID- 24579411
TI  - The intensity of QuantiFERON TB-gold response does not differentiate active from
      latent tuberculosis.
AB  - We analyzed positive QuantiFERON (QFT) assays, performed between July 2009 and
      April 2011 in the Mercy University Hospital, Cork, Ireland, which included, 94
      patients with latent tuberculosis (LTBI) and 35 patients with active
      tuberculosis. There was no difference in the intensity of response between
      patients with LTBI and active tuberculosis (p = 0.1589). In patients with LTBI,
      there were no correlations between age (p = 0.353), sex (p = 0.476), smoking (p =
      0.323), contact (p = 0.612), Mantoux response (p = 0.055), Irish nationality
      (p=0.768), previous BCG vaccination (p = 0.504), WCC (p = 0.187), lymphocyte
      count (p = 0.786), neutrophil count (p = 0.157) and the intensity of QFT
      response. Similarly in patients with active TB, there were no correlations
      between these variables and QFT response. The intensity of QFT response does not
      help to differentiate active from LTBI. The intensity of QFT response is not
      influenced by age, sex, smoking, remoteness of contact history, Mantoux response,
      nationality, CXR abnormalities, BCG vaccination and peripheral lymphocyte count.

PMID- 24579412
TI  - Routine obstetric ultrasound services.
AB  - Antenatal ultrasonography is widely used in pregnancy to assess fetal growth,
      wellbeing and anatomy. Although ultrasound screening is now an integral part of
      routine antenatal care, recommendations for the delivery of obstetric ultrasound
      vary from country to country. A recent survey of English maternity units reported
      that 100% of women are offered routine mid-trimester fetal anomaly scanning, in
      line with expert recommendations. Currently in Ireland, no national guidance
      exists to inform practitioners on the minimum standards for obstetric ultrasound
      practice. In 2012, we conducted a structured telephone survey of all 20 maternity
      units in Ireland (n = 74,377 births). Routine mid-trimester anomaly scanning was
      offered universally to all women in 7/20 (35%) units, offered selectively to some
      women in 9/20 (45%) units and not offered to any women in 4/20 (20%) of units.
      The time allotted for a complete fetal anatomical survey was 10-15 minutes in
      4/16 (25%) units, 20 minutes in 7/16 (44%) units and 25-30 minutes in 5/16 (31%)
      units. Written guidelines on the appropriate management of "soft markers" for
      fetal aneuploidy were routinely used in 11/16 (69%) of units. In no Irish unit
      currently, are images from fetal anomaly scanning routinely reviewed by an
      Obstetrician with an interest in fetal medicine. 19/20 (95%) of respondents
      believed that a minimum of 2 scans should be offered in routine uncomplicated
      pregnancies. Improvements in the availability of obstetric ultrasound to pregnant
      women in Ireland will require increased staffing numbers at both the
      ultrasonographer and fetal specialist levels. There is a clear need for national
      guidelines on the provision of routine obstetric ultrasound in Ireland.

PMID- 24579414
TI  - The changing epidemiology of the bronchiolitis epidemic in Tallaght Hospital.
AB  - Bronchiolitis affects one third of babies in their first year of life. We
      investigated all bronchiolitis admissions to Tallaght Hospital in the last five
      years, with the hope of providing an insight into the epidemic in an Irish
      population. We analysed these 1,202 admissions on the basis of time of year
      (busiest being December at 24.20%), length of stay (mean 2.92 days), gender (62%
      male) and age (mean 30.29 weeks). There was a 102% increase in the average
      incidence of bronchiolitis in the first six months of 2011 and 2012 (186)
      compared to the previous four years (92.25). P value was statistically
      significant at 0.0469. Our findings were backed up by comparable data from OLCH,
      Crumlin (149.5 for 2011-2012 vs 36.25 for 2007-2010). There has been in a
      significant shift in the timing and incidence of bronchiolitis in Tallaght
      Hospital in the last two years. We explored the possible reasons for this, with
      special attention to RSV incidence, climate causes and vaccine programs.

PMID- 24579413
TI  - Clinical tetanus in an 11 year old boy.

PMID- 24579416
TI  - Validation of the VitalPACTM early warning score (ViEWS) in acutely ill medical
      patients admitted.

PMID- 24579415
TI  - Safety comes first: are doctors attentive enough to their initial clinical
      assessment notes?
AB  - Accurate hospital admission/initial history and physical examination [H&P] notes
      are vital to support patient care. We aimed to assess the quality of H&P notes
      and to compare medical/surgical, and inpatient/outpatient H&P notes. A cross
      sectional study examined 154 initial H&P notes for the adherence to a standard
      protocol in a tertiary referral hospital. 134 doctors (87.1%) adhered to the
      correct layout in accordance with the standard. Only 77 doctors (50%) recorded
      the names of the patient's medications. 106 (68.8%) documented the allergy
      status. Six doctors (3.9%) omitted an objective record of their own identity.
      Surgeons were superior at recording admission type (p = 0.0001) and past surgical
      history (p = 0.002) only. The data in this study show that the standard o
      completeness of the H&P documentation among doctors is suboptimal. We recommend
      the introduction of a standardised H&P template to reduce errors.

PMID- 24579417
TI  - The leaders of the ADA and the FDA are committed to making members successful!

PMID- 24579418
TI  - It's licensure renewal time again...What's all the fuss about?

PMID- 24579420
TI  - What is so stressful about practicing dentistry?

PMID- 24579419
TI  - How can you give back to your community?

PMID- 24579421
TI  - The two questions the most valuable team members ask.

PMID- 24579422
TI  - Born to lead...Terry Buckenheimer.

PMID- 24579423
TI  - Short in stature, but larger than life.

PMID- 24579424
TI  - Q & A with the Dentist of the Year, Dr. Idalia Lastra.

PMID- 24579425
TI  - Diagnostic discussion. Median rhomboid glossitis (MRG).

PMID- 24579427
TI  - Your peer review program: how it works.

PMID- 24579426
TI  - Fluoridation: the debate goes on.

PMID- 24579428
TI  - Mediation makes sense.

PMID- 24579429
TI  - If peer review fails, can the records be used against you?

PMID- 24579431
TI  - "Your team's personal appearance".

PMID- 24579430
TI  - At present, Florida's Medicaid is limited to children up to 21 years old.

PMID- 24579433
TI  - Safety and feasibility of single-catheter ablation using remote magnetic
      navigation for treatment of slow-fast atrioventricular nodal reentrant
      tachycardia compared to conventional ablation strategies.
AB  - OBJECTIVE: Ablation of atrioventricular nodal re-entrant tachycardia (AVNRT) is a
      highly effective procedure both with radiofrequency (RF) and cryoenergy (CE).
      Conventionally, it requires several diagnostic catheters and hospital admission.
      This study assessed the safety and efficacy of a highly simplified approach using
      the magnetic navigation system (MNS) compared to CE and manual RF ablation (MAN).
      METHODS AND RESULTS: In the MNS group a single magnetic-guided quadripolar
      catheter was inserted through the internal jugular vein to perform ablation. In
      the CE group cryomapping preceded ablation and for MAN procedures conventional
      ablation was performed. The following parameters were analysed: success- and
      recurrence rate, procedure-, fluoroscopy- and total application time. In total 69
      eligible patients were treated with MNS (n = 26), CE (n = 25) and MAN (n = 16).
      The success rates were 100%, 100% and 94%, respectively (p = ns). The mean
      procedural time was 83 +/- 25 min for MNS, 117 +/- 47 min for CE and 117 +/- 55
      min for MAN (P < 0.01). Total radiation time was significantly lower for MNS [0.0
      min (IQR 0.0-0.0)] compared to CE [15.1 min (IQR 9.1-23.8), P < 0.001] and MAN
      [17.5 min (IQR 7.0-31.3), P < 0.001]. The total application time was comparable
      for both RF groups: 357 +/- 315 s (MNS) vs 204 +/- 177 s (MAN) (P = 0.14). No
      major adverse events occurred. After 3 months follow-up similar PR intervals were
      recorded for all patients. During a follow-up of 26 +/- 5 months recurrence rates
      were 3.8%, 4.0% and 6.3%, respectively, for each group. CONCLUSIONS: The MNS
      guided single-catheter approach is a feasible and safe technique for the
      treatment of patients with typical AVNRT.

PMID- 24579432
TI  - Transcatheter left atrial appendage closure for stroke prevention in atrial
      fibrillation with Amplatzer cardiac plug: the Belgian Registry.
AB  - AIMS: The aim of the present study was to evaluate the procedural feasibility,
      the safety and the 1-year outcome following left atrial appendage (LAA) closure
      using the Amplatzer cardiac plug (ACP) in Belgium. METHODS AND RESULTS: Data were
      prospectively collected among 90 consecutive patients, undergoing LAA closure
      with an ACP in 7 Belgian centres between June 2009 and September 2012. The
      patients (56 males, 74 +/- 8 years) were at high risk for stroke (CHA2DS2-VASc =
      4.4 +/- 1.8) and bleeding (HAS-BLED = 3.3 +/- 1.3).Technical success was obtained
      in all but one patient and procedural success was 95%. Procedural major adverse
      events (MAE) were 3 tamponades resulting in death in one case. Minor
      complications were 3 insignificant pericardial effusions, 2 transient myocardial
      ischaemia due to air embolism and 1 femoral pseudoaneurysm. At 1-y follow-up,
      there were 4 deaths, 2 minor strokes, 1 tamponade and 1 myocardial infarction.
      Overall survival was 94% and freedom from MAE was 88%. In our population, the
      expected annual stroke risk according to the CHA2DS2-VASc score was 5.08%, while
      the observed stroke rate was 2.14%/year. CONCLUSIONS: The Belgian registry shows
      that LAA closure using the ACP device is feasible and safe. At 1-y follow-up, the
      observed stroke rate was 2.14%/year, less than predicted by the CHA2DS2-VASc
      score. Longer follow-up is needed to evaluate the long-term safety and its
      efficacy in reducing stroke.

PMID- 24579434
TI  - Impact of metabolic syndrome on fractional flow reserve.
AB  - OBJECTIVE: Fractional flow reserve (FFR) assessment is widely used to determine
      significance of intermediate coronary lesions. Previously, components of the
      metabolic syndrome (MS) which may affect FFR validity were not tested
      cumulatively. In this study, we investigate the possible effect of MS on FFR
      assessment. METHODS AND RESULTS: We retrospectively evaluated 178 consecutive
      patients who had undergone FFR assessment. Thirty-two patients were excluded. All
      of the coronary lesions were in the left anterior descending artery. They were
      evaluated with quantitative coronary angiography (QCA). In 105 patients the MS
      was present and 41 patients were without the MS. According to the severity of the
      coronary lesions in QCA, patients were divided into three groups: 40-50%, 51-60%
      and 61-70% lesions. FFR measurements were compared in each group with respect to
      MS presence. Coronary artery lesions were accepted as haemodynamically
      significant if FFR < or = 0.80. Age of the population, lesion length, lesion
      diameter and adenosine dosage performed during FFR assessment were not different
      between patients with MS or without MS. When the lesions were divided into three
      categories according to the severity of the luminal narrowing expressed in
      stenosis percentages as 40-50, 51-60, and more than 61%, the observed FFR values
      decreased with advancing lesion category (P = 0.04). However, observed FFR values
      did not differ between the patients with MS and without MS in each category (P =
      0.88). After exclusion of the diabetic patients, FFR values still did not differ
      between the patients with MS and without MS in each category (P = 0.78).
      CONCLUSIONS: Presence of the metabolic syndrome has no significant effect on FFR
      assessment. This study provides additional data for the reliability of FFR in
      patients with MS.

PMID- 24579435
TI  - The prognostic effect of different types of cardiac rehabilitation in patients
      with coronary artery disease.
AB  - AIM: The purpose of this study was to access and compare the prognostic effects
      of different types of cardiac rehabilitation (CR) in patients with chronic
      coronary artery disease. METHODS: One hundred fifty-two patients were
      retrospectively divided into 4 groups according to their adherence to physical
      activity recommendations. Patients in groups 1 and 2 participated in the guided 3
      month exercise programme. Patients in group 1 then continued with individual
      exercise training, while patients in the group 2 stopped exercising after
      finishing the guide exercise programme. Patients in group 3 participated only in
      individual exercise training throughout the whole follow-up period, and patients
      in group 4 declined all exercise recommendations and did not exercise. The
      prognostic outcome of different types of cardiac rehabilitation was compared
      among the groups. In addition, patients who participated in individual exercise
      training according to recommendations (cohort IT+) were compared with patients
      who declined these activities (cohort IT-). RESULTS: During a median follow-up of
      94 months, 33 deaths occurred: 17 cardiovascular and 16 non-cardiac deaths. A
      Kaplan-Meier survival analysis demonstrated significantly better survival rates
      for patients who followed a long-term aerobic exercise training (IT+) than for
      those who did not participate or who had only a short-term exercise programme (IT
      ) (P = 0.009). CONCLUSION: In our study, long-term exercise training had a higher
      impact on patient survival than short-term guided CR.

PMID- 24579436
TI  - Aortic stenosis: right and left ventricular function in the early postprocedural
      phase. Comparison between transcatheter and surgical aortic valve implantation.
AB  - BACKGROUND: While impact of surgical aortic valve replacement (SAVR) on the
      function of the right and left ventricle (RV, LV) has been studied extensively,
      the objective of this study was to compare the two different transcatheter
      approaches, transfemoral vs. transapical aortic valve implantation (tf-AVI, ta
      AVI) and SAVR with respect to postoperative recovery of RV and LV function in
      patients with severe aortic stenosis. METHODS AND RESULTS: Conventional
      echocardiographic studies were performed before and after the procedure (< 8
      days) in 74 consecutive patients undergoing tf-AVI, 88 with ta-AVI and 63
      surgically treated patients. Post procedure, a marked deterioration in the
      tricuspid annular plane systolic excursion (TAPSE) was seen after SAVR (23.7 +/-
      4 mm vs. 15.6 +/- 2.9 mm, P > 0.001) and ta-AVI (21.1 +/- 4.7 mm vs. 19.1 +/- 4.7
      mm, P = 0.02), while TAPSE remained unchanged in the tf-AVI group (21.7 +/- 5 mm
      vs. 22.1 +/- 4.9 mm, P = 0.38). Additionally, a significant drop of the visually
      estimated right ventricular ejection fraction in the SAVR and ta-AVI group
      compared to tf-AVI could be seen (P < 0.001, P = 0.003, respectively) Among
      patients with a pre-existing reduced LV-function, despite similar baseline LVEF
      (38.5 +/- 7.1% vs. 37.4 +/- 5.6, P = 0.8), tf-AVI patients had better recovery of
      LVEF compared with ta-AVI (ALVEF 7.2 +/- 8% vs. 1.6 +/- 9.3%, P = 0.038).
      CONCLUSION: Our study underlines the less invasive nature of tf-AVI, causing less
      intraoperative trauma and pericardial adhesions to the heart. Given that acute RV
      failure after cardiac surgery remains a major cause of morbidity and mortality,
      the results of the present study suggest that in high-risk patients, TAVI and in
      particular tf-AVI could be favoured over SAVR in regard to a RV dysfunction.

PMID- 24579437
TI  - Predicting the outcomes of acute ischaemic stroke in atrial fibrillation: the
      role of baseline CHADS2, CHA2DS2-VASC and HAS-BLED score values.
AB  - OBJECTIVE: Atrial fibrillation (AF)-related risk of stroke is commonly assessed
      using the CHADS2 or CHA2DS2-VASc score, whilst the oral anticoagulation-related
      bleeding risk can be estimated by the HAS-BLED score. We investigated the
      association of these scores with outcomes of AF-associated strokes, defined as
      symptomatic intracranial haemorrhage (sICH), favourable outcome (modified Rankin
      Scale [mRS] 0-2) or death. METHODS: Analyses of prospective data on stroke
      patients with non-valvular AF treated in the Stroke Unit from January 2009 to
      June 2012 were performed. RESULTS: Of 787 patients with an acute ischaemic
      stroke, 131 had AF (16.6%, median age 70, range 62-76 years). Of those, 6
      patients (4.6%) had sICH, 49 (37.4%) died and 55 (42.0%) had a favourable 90-day
      outcome. HAS-BLED score of > or = 3 was associated with sICH both in the
      univariate analysis (OR 15.13; 95% CI 2.11-108.25, P = 0.007) and in the
      multivariable model (OR 19.96; 95% CI 2.23-178.81, P = 0.007), which also
      included the baseline neurological deficit score (NIHSS), intravenous
      thrombolysis or the use of antiplatelet/anticoagulant therapy. The CHADS2 and
      CHA2DS2-VASc scores were associated with 90-day mortality in the univariate
      analyses (OR 1.47; 95% CI 1.11-1.95 and OR 1.36; 95% CI 1.08-1.69, respectively,
      both P = 0.008). The CHA2DS2-VASc score was inversely related to the favourable
      outcome in the univariate analysis (OR 0.80; 95% CI 0.65-0.99, P = 0.042).
      CONCLUSION: HAS-BLED was found to have an independent predictive value on the
      occurrence of sICH regardless of the treatment (thrombolysis or conservative
      therapy). A trend toward statistical relation to the influence of the CHA2DS2
      VASc values on the favourable outcome was registered.

PMID- 24579438
TI  - Impact of frailty scores on outcome of octogenarian patients undergoing
      transcatheter aortic valve implantation.
AB  - BACKGROUND: For selected patients with symptomatic aortic stenosis, transcatheter
      aortic valve implantation (TAVI) is an alternative to surgical aortic valve
      replacement (AVR). In addition to co-morbidities, frailty has to be taken into
      account in the decision-making process. Criteria for patient selection, according
      to current guidelines, include EuroSCORE and STS score but frailty is not easy to
      quantify. ISAR (Identification of Seniors At Risk) detects seniors at risk for
      adverse health outcome after an emergency visit and SHERPA (Score Hospitalier
      d'Evaluation du Risque de Perte d'Autonomie) assesses the risk of functional
      decline after hospitalization. OBJECTIVES: The aim of the present study was to
      evaluate the impact of ISAR and SHERPA scores in the prediction of patient
      outcome afterTAVI. METHODS AND RESULTS: A prospective cohort of 30 consecutive
      octogenarian patients (16 males, 86 +/- 3 y, EuroSCORE 34 +/- 12%) underwent a
      transfemoral TAVI and a complete geriatric assessment in our institution.
      Survival at one year was 73%. The ISAR score was similar between both groups (3.1
      +/- 1 vs. 3.6 +/- 1; P = 0.10) but the SHERPA score was significantly higher in
      non-survivors (7.8 +/- 1.6) than among survivors (4.9 +/- 2.4; P = 0.001). With
      multivariate analysis, SHERPA score and BMI were independent predictors of 1-year
      mortality. Kaplan-Meier analysis showed that 1-year survival was significantly
      lower in patients with than in those without a SHERPA score > 7 (40 vs. 89%; P =
      0.004). CONCLUSIONS: The result of this study showed that SHERPA score predicts 1
      year survival after transfemoral TAVI and could be considered as a useful frailty
      score in patient selection.

PMID- 24579439
TI  - Post-exercise heart rate variability recovery: a time-frequency analysis.
AB  - OBJECTIVE: Most studies investigating the effects of non-pharmacological
      interventions, such as physical training (PT), on cardiac autonomic control,
      assessed the HRV only in resting conditions. Recently, a new time-frequency
      mathematical approach based on the short-time Fourier transform (STFT) method has
      been validated for the assessment of HRV in non-stationary conditions such as the
      immediate post-exercise period. The aim of this study was to evaluate the effects
      of the PT on post-exercise cardiac autonomic control using the time-frequency
      STFT analysis of the HRV. METHODS: Twenty-one healthy male volunteers
      participated in this study. The subjects were initially evaluated for their
      physical exercise/sport practice and allocated to groups of low physical training
      ((Low)PT, n = 13) or high physical training (H(igh)PT, n = 8). The post-exercise
      HRV was assessed by the STFT method, which provides the analysis of dynamic
      changes in the power of the low- and high-frequency spectral components (LF and
      HF, respectively) of the HRV during the whole recovery period. RESULTS: Greater
      LF (from the min 5 to 10) and HF (from the min 6 to 10) in the post-exercise
      period in the H(igh)PT compared to the (Low)PT group (P < 0.05) was observed.
      CONCLUSION: These results indicate that exercise training exerts beneficial
      effects on post-exercise cardiac autonomic control.

PMID- 24579440
TI  - Home-based cardiac rehabilitation decreases red cell distribution width in
      chronic heart failure.
AB  - OBJECTIVE: Red cell distribution width (RDW) is a measure of variation in the
      volume of circulating erythrocytes and has recently emerged as a powerful
      prognostic marker in heart failure. We studied the effect of 5-month, home-based
      cardiac rehabilitation on RDW. METHODS AND RESULTS: Sixty-two patients (age:
      median 67 years, IQR 63-74) with chronic heart failure caused by reduced left
      ventricular systolic function were enrolled. Exercise time and physical activity
      levels out of the hospital were determined by a single-axial accelerometer.
      Baseline RDW values were: median 13.6, IQR 12.8-14.4%, with 13 patients (21.0%)
      showing values above the upper normal limit. RDW values were decreased
      significantly after training in the 13 patients with elevated baseline RDW values
      (P < 0.01), but not in the remaining 49 patients with normal baseline RDW values.
      There was a highly significant correlation between baseline RDW and changes in
      RDW after exercise training (P = 0.0001, r2 = 0.628, n = 62). The time spent for
      moderate (> 3 METs) exercise was: median 9.0, IQR 3.0-18.8 minutes per day.
      CONCLUSIONS: Relatively low intensity, home-based cardiac rehabilitation was
      associated with decreased RDW in heart failure patients with abnormal RDW.

PMID- 24579441
TI  - The potential role of local voltage potentials in right ventricular outflow tract
      arrhythmias: 47 cases with ventricular arrhythmias originating from right
      ventricular outflow tract.
AB  - OBJECTIVE: The object of this study was to investigate the possible role of local
      voltage potentials (LVPs) in mapping the ventricular arrhythmias originating from
      right ventricular outflow (RVOT). METHODS: Forty-seven patients with RVOT VAs
      (ventricular arrhythmias), referred for radiofrequency catheter ablation to our
      hospital, were analysed retrospectively for the prevalence, characteristics and
      electrophysiological evaluation of the LVPs recorded in successful and
      unsuccessful ablation sites. RESULTS: Radiofrequency ablation was successful
      immediately in all the 47 cases. Catheter ablation was performed at a mean of 8
      +/- 6 sites per patient. There were 58 effective ablation sites, 5 cases with
      changing morphology of ventricular arrhythmias (VAs), and 318 invalid ablation
      sites. Activation times at effective ablation sites were slightly earlierthan
      those at invalid ablation sites (-28 +/- 8 ms vs-24 +/- 7 ms, P < 0.05). The LVPs
      appeared during VAs in 47 sites of the 58 effective ablation sites (81.0%), far
      more than the 22 sites of the 318 invalid ablation sites (6.9%) (P < 0.01). In
      two cases VAs recurred during follow-up. They received a second catheter
      ablation. CONCLUSIONS: Local ventricular potentials can be recorded in most
      patients with idiopathic VAs originating from the right outflow tract.The local
      potentials may facilitate successful radiofrequency ablation.

PMID- 24579442
TI  - Pericardial involvement in systemic lupus erythematosus: current diagnosis and
      therapy.
AB  - Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that can
      affect almost any organ system. Cardiac involvement is common and has been
      acknowledged as a primary cause of morbidity and mortality in patients with SLE.
      Pericarditis is the most common cardiovascular manifestation in SLE. In this
      review we present the current diagnosis and treatment of SLE-related pericardial
      involvement.

PMID- 24579443
TI  - Vasovagal syncope initiating ventricular fibrillation in a healthy subject.
AB  - A 62-year-old man with cured lymphoma as only significant medical history
      experienced a first reflex syncope after prolonged orthostatic posture, with
      cardiac arrest. Prolonged asystole was followed by ventricular fibrillation
      needing external defibrillation. The defibrillator provided complete recordings.
      Thorough investigation revealed no cardiac abnormalities apart from a few right
      ventricular outflow tract premature complexes. This patient benefitted from
      implantation of an ICD for ventricular fibrillation secondary to reflex syncope,
      usually considered benign.

PMID- 24579444
TI  - Cutting balloon angioplasty for in-stent restenosis of the aortic coarctation in
      a young boy presenting with systemic hypertension of the upper extremities.
AB  - An 8.25-year-old boy was incidentally found to have systemic hypertension of the
      upper extremities. Blood pressures of the upper extremities were 142-150/86-98
      mmHg, and those of the lower extremities 110-116/60-66 mmHg. Doppler
      echocardiography showed in-stent restenosis of the aortic coarctation.
      Traditional high-pressure balloon angioplasty failed to dilate this inveterate in
      stent restenosis. Instead, a cutting balloon angioplasty was performed. The lumen
      was dilated from 4.80 mm to 7.89 mm. The pressure gradient dropped from 32 mmHg
      to 9 mmHg. Blood pressures of the upper extremities were 112-116/76-78 mmHg, and
      those of the lower extremities 100-104/70-72 mmHg. This paper highlights that a
      cutting balloon angioplasty can serve as a juste milieu to relieve in-stent
      restenosis of the aortic coarctation when traditional high-pressure balloon
      angioplasty is debatable.

PMID- 24579445
TI  - Pacemaker insertion in a patient with persistent left superior vena cava.
AB  - A persistent left superior vena cava (PLSVC) is a rare and usually unnoticed
      congenital anomaly. However, clinicians must be conscious of its existence as a
      PLSVC can be associated with other anomalies of cardiovenous morphology with
      significant clinical implications for transvenous procedures. We report a case of
      a double superior vena cava with absent innominate vein found during
      catheterization for cardiac resynchronization pacemaker therapy implantation (CRT
      P). We also describe a technique used for successful positioning of the leads
      into the right atrium and right ventricle.

PMID- 24579447
TI  - Championing cardiovascular health innovation in Europe.

PMID- 24579448
TI  - [Not Available].

PMID- 24579446
TI  - Compression of the right ventricle by the liver through a diaphragmatic hernia
      after right gastroepiploic artery coronary bypass grafting.

PMID- 24579449
TI  - [Rapid identification of ESBL--positive clinical samples using real-time PCR
      method].
AB  - OBJECTIVES: A new method has been developed for detecting genes determining the
      extended-spectrum beta-lactamase (ESBL) phenotype directly from patients'
      clinical material. The method enables detection of the bla(CTX-M) gene encoding
      CTX-M beta-lactamases and the bla(SHV) gene variants with real-time PCR
      technology using locked nucleic acid oligonucleotides. MATERIAL AND METHODS: In
      this pilot study, tracheal aspirates obtained from patients with mechanical
      ventilation hospitalized at Department of Anaesthesiology and Resuscitation of
      the University Hospital in Olomouc between 1st March and 30th December 2010
      period were tested. Each sample was identified with standard microbiological
      procedures including phenotypic determination of ESBL-positive enterobacteria. At
      the same time, each sample was analyzed for the presence of nucleic acids (DNA)
      which encode CTX-M and SHV ESBL using real-time PCR. RESULTS: 150 samples of
      tracheal aspirates from 71 patients were included into testing. In the set, 13
      (8.7%) ESBL-positive samples were identified by culture methods while 27 (18 %)
      positive samples were identified by the real-time PCR method. Of the 27 PCR
      positive samples, 24 were positive for the bla(CTX) gene; in 2 samples, the ESBL
      bla(SHV) gene was detected, and both genes were present in 1 sample. All culture
      positive samples were also PCR-positive for the presence of bla(CTX) and/or
      bla(SHV) sequences. CONCLUSIONS: The new real-time PCR assay is likely to shorten
      the time for detection of enterobacteria producing SHV and CTX-M beta-lactamases
      from 48 to 6 hours. It enables ESBL-positive enterobacteria determination in
      tracheal aspirates of patients suffered from life-threatening nosocomial
      pneumonia where the early introduction of adequate antimicrobial treatment plays
      the important role.

PMID- 24579450
TI  - [The use of electron microscopy and virus isolation in the diagnosis of aseptic
      neuroinfections].
AB  - OBJECTIVE: In aseptic neuroinfections, the etiology is usually known in 50-70% of
      cases. The aim was to increase the rates using electron microscopy (EM) and virus
      isolation in cell cultures. MATERIAL AND METHODS: The prospective study included
      34 patients with aseptic neuroinfections hospitalized at the Department of
      Infectious Diseases in Ostrava fromJuly to November 2012. EM examined
      cerebrospinal fluid of all patients and virus isolation in tissue cultures was
      performed in all cerebrospinal fluid samples. Cerebrospinal fluid was examined by
      polymerase chain reaction for enteroviruses in 30 patients and for herpes simplex
      virus 1 and 2 in 29 patients. Detection of antibodies against Borrelia
      burgdorferi and tick-borne encephalitis was performed in all 34 patients.
      RESULTS: Possible etiological agents were discovered in 31 out of 34 patients
      (91%), with one agent being found in 23 patients (68%) and two agents being
      detected in 8 patients (24%). EM revealed the agents in 26 patients and virus
      isolation was successful in 10 patients. EM was the only method to identify 10
      agents. A group of 23 patients with a single agent detected included 14 patients
      with enteroviral meningitis, 4 patients with Lyme borreliosis and 4 patients with
      tick-borne encephalitis; EM detected an undefined virus in the last patient. An
      unusual group of 8 patients with two agents detected comprised 5 patients with
      enteroviruses and spirochetes, 2 patients with tick-borne encephalitis and
      undefined viruses and 1 patient with a spirochete and an undetermined virus.
      CONCLUSION: EM can aid in explaining the etiology of aseptic neuroinfections.
      However, the clinical interpretation of results remains problematic, such as
      detection of unknown viruses or two possible agents in 8 out of 34 patients.

PMID- 24579451
TI  - [Experience with laboratory diagnosis of Clostridium difficile].
AB  - BACKGROUND: Clostridium difficile is currently a significant cause of nosocomial
      diarrhea. For several years, the number of infectious cases in the community has
      also been increasing. Since the beginning of 2010, quite a large increase in the
      number of Clostridium difficile infections (CDIs) has been noted in Pardubice
      Regional Hospital (PRH). The objectives of this study were to describe and
      evaluate the methods used in the laboratory diagnosis of CDIs in PRH, and to
      describe the laboratory diagnostic algorithm used here. MATERIAL AND METHODS:
      Samples of stools were taken from symptomatic patients hospitalized or examined
      in the outpatient departments of PRH from 1 July 2010 to 31 December 2012. For
      the detection of glutamate dehydrogenase (GDH) and toxin A/B, the dual test based
      upon the principle enzyme immunoassays C. Diff Quik Chek Complete, Techlabo (D
      EIA) was used. The system GeneXpert PCR Cepheid (PCR) was used for confirmation
      of laboratory findings. Since the beginning of 2011, all the GDH-positive samples
      were cultured. RESULTS: A total of 2,040 samples were examined. The D-EIA test
      was used for examination of 2,014 samples. Of those, 1,373 (68.2 %) samples were
      GDH- and toxin A/B-negative. In 359 (17.8 %) samples, both GDH and toxin A/B were
      detected. The D-EIA sensitivity and specificity for detecting toxigenic strains
      in stool samples were 21.8% and 97.2%, respectively. The PPV and NPV rates
      calculated for the populations with prevalence rates of disorders of 5%, 10%, 20%
      and 50 % were 0.29, 0.46, 0.66, 0.88 and 0.96, 0.92, 0.83, 0.55, respectively.
      The sensitivity and specificity of GDH for the detection of Clostridium difficile
      in stools were 100.0% and 96.2%, respectively. PCR examination was carried out in
      140 samples. Of those, 82 samples were PCR-positive. The gene for the production
      of toxin B was detected in 47%, the finding suspected for ribotype 027 (gene for
      toxin B, binary toxin and deletion of tcdC) in 48%. In 5% of the samples, the
      gene for toxin B and the gene for the binary toxin were detected. CONCLUSION:
      Considering the low sensitivity of the D-EIA test for detecting the toxigenic
      strain of Clostridium difficile, if used as the only one, a two-step algorithm
      was introduced for routine laboratory examination of infections with Clostridium
      difficile in the Clinical Microbiology Department of PRH. In the first step, the
      D-EIA test diagnosed 86 % of examined samples in 30 minutes as positive (GDH +;
      toxin A/B +) or negative (GDH -; toxin A/B -). The examination with PCR in the
      second step increased the number of patients diagnosed with CDI. The test results
      are available within two hours. This enables quick introduction of isolation
      measures in the departments of PRH and appropriate antibiotic treatment of the
      patients.

PMID- 24579452
TI  - [Small colony variants Staphylococcus aureus].
AB  - The phenomenon of dwarf colonies of S. aureus, the so-called small colony
      variants (SCVs), is associated with chronic and recurrent staphylococcal
      infections. Most frequently, these phenotypic variants differ from normal strains
      of S. aureus in colony size, morphology, pigmentation and other characteristics
      as well as molecular genetic changes. SCVs frequently emerge as a result of
      mutations in metabolically important and regulatory genes. The mutations are a
      cause of SCVs auxotrophy. From a clinical point of view, an increased ability of
      SCVs to resist antibiotic therapy and also an ability to persist within
      eukaryotic host cells are of importance.

PMID- 24579453
TI  - [Cytomegalovirus and its relationship to chronic inflammatory bowel diseases and
      tumors].
AB  - Human cytomegalovirus (hCMV), a member of the Betaherpesvirinae subfamily, was
      long considered an important pathogen especially in immunocompromised hosts,
      mainly in post-transplant patients receiving immunosuppressive therapy. Results
      of many studies from the last decade suggest that cytomegalovirus is a very
      important pathogen having a greater association with many other diseases. The
      relationship of hCMV to chronic inflammatory bowel diseases, ulcerative colitis
      and Crohn's disease, has been long studied but results of the studies have been
      rather inconclusive. Interestingly, hCMV was found to be more prevalent in
      lesions of severe ulcerative colitis, in particular ulcerative colitis refractory
      to immunosuppressive therapy (40-57% in results from clinical studies) than in
      mild or moderate colitis (up to 5% in most studies). Another group of diseases
      possibly related to hCMV is tumors. Numerous studies discuss the oncomodulatory
      role of hCMV in malignant glioblastoma, colorectal adenocarcinomas, prostate
      cancer and lymphomas. Despite extensive evidence suggesting a possible
      relationship of hCMV to some tumors, such as successful induction of malignant
      carcinoma by hCMV latent infection in animal models, hCMV has not been classified
      as an oncovirus. However, its potential in this respect is apparent.

PMID- 24579454
TI  - [Primary meningococcal conjuctivitis with the development of a systemic disease].
AB  - Neisseria meningitidis is a rare cause of acute bacterial conjunctivitis.
      Systemic meningococcal disease follows meningococcal conjunctivitis in
      approximately one quarter of patients. Systemic antibiotic treatment is indicated
      in the case of meningococcal conjunctivitis to prevent spread of infection. We
      report 6-month-old boy who presented with meningococcal conjunctivitis and
      developed sepsis and meningitis in 24 hours. The course of the disease was
      favorable.

PMID- 24579455
TI  - [Quality of life of leprosy patients' group in Vietnam].
AB  - Vietnam has achieved WHO's leprosy elimination goal at a national level, but
      there are a lot ofex-leprosy patients who have severe physical disabilities in
      the leprosy treatment centers and resettlement villages. The purpose of this
      study is to analyze the quality of life (QOL) of ex-leprosy patients in Vietnam.
      The study was conducted in two leprosy treatment centers in Vietnam. The SF-36v2
      QOL survey was used to evaluate the leprosy patients' health related conditions,
      and as a comparison group, SF-36v2 QOL survey was provided to a random group from
      the general population to measure the general groups' health related conditions.
      For those participants aged from 10 to 29 years old, the patients' group scored
      lower than the general group in each of the following categories; Role physical,
      Bodily pain, General health perceptions, Vitality, Social functioning, Role
      emotional. On the other hand, middle aged and elderly participants were found to
      show no significant difference between the patients' group and the general group.
      In comparing the two leprosy treatment centers, the score of Role physical and
      Role emotional were significantly higher in the leprosy treatment center where
      vocational training programs for leprosy patients are offered. From these
      results, the use of vocational training program is one of the effective methods
      for improving the QOL of the patients' group.

PMID- 24579456
TI  - [International cooperation with the neglected tropical disease Buruli ulcer in
      Togo].
AB  - The objectives of this paper are to grasp the current status of an endemic
      disease, known as Buruli ulcer (BU), in the Republic of Togo and the expansion of
      international assistance in the field. By adopting the explicit support model,
      this paper also compares the obtained research results with those of the Republic
      of Ghana and Benin, to clarify the primary functions played among respective
      governments, WHO, and NGO. Under the auspices of the WHO Global Buruli Ulcer
      Initiative (GBUI, 1998-), National Buruli Ulcer Control Programme (NBUCP) in the
      Togo was initiated in 1999. However, due to the shortage of national budget and
      politico-economic instabilities of the nation, the actual implementation of NBUCP
      proved to be problematic. It was after 2007 that the programme began to move
      forward with the interventions of NGOs like DAHW and Handicap International.
      Currently, major players involved in the implementation of the policies provided
      by the GBUI are WHO, NGOs and the targeted governments. In other words, the
      organizations involved in BU treatment work together by fulfilling their
      functions. Unlike the neighboring countries, the Togolese government encountered
      much difficulty in materializing its national programme. Largely due to the
      political instability and the severe shortage of national budget, stronger
      assistances from NGOs were required at various levels of the national health
      measures from formulating to implementing the programme. As the programmes in
      Togo and Ghana/Benin expanded over the years, the respective support model
      revealed to be unique and different. In Ghana and Benin, intimate cooperation
      among WHO, government and NGOs has been established. In Togo, strengthening of
      collaboration among the three players is expected.

PMID- 24579457
TI  - [Development of a novel recombinant BCG for tuberculosis vaccine].
AB  - A novel recombinant BCG (BCG-DHTM), that was deficient in urease, expressed with
      gene encoding the fusion of BCG-derived HSP70 and M. tuberculosis-derived major
      membrane protein (MMP)-II, was constructed for use as a vaccine against
      tuberculosis. BCG-DHTM efficiently activated dendritic cells (DC) to induce
      cytokine production, including IL-12, TNFalpha and IL-1beta and phenotypic
      changes. The DC infected BCG-DHTM was more potent in activation of native T cells
      of CD4 and CD8 subsets than those infected vector control BCG. The activation of
      naive T cells by BCG-DHTM was closely associated with phagomal maturation, and
      that of naive CD8+ T cells by BCG-DHTM was induced by the activation of cytosolic
      cross-presentation pathway. Further, BCG-DHTM seemed to activate native CD4+ T
      cells and native CD8+ T cells by antigen-specific fashion. The primary infection
      of BCG-DHTM in C57BL/6 mice for 12 weeks efficiently produced T cells responsive
      to in vitro secondary stimulation with MMP-II, HSP70 and H37Rv-derived cytosolic
      protein and inhibited with multiplication of subsequently challenged M.
      tuberculosis in lungs at least partially. The effect of BCG-DHTM as a vaccine for
      tuberculosis is not fully convincing and need the improvement, however, our
      strategy in the development of new recombinant BCG for tuberculosis seems to
      provide useful tool.

PMID- 24579458
TI  - [Towards novel tuberculosis and leprosy vaccine development: the role of Th1
      inducing peptide in cytotoxic T cell differentiation].
AB  - The effectiveness of a vaccine against tuberculosis and leprosy is mainly judged
      by its capability to induce memory CD8 cytotoxic T cells (CTL). It has been
      reported that 'help' from CD4+ T cells is required to induce memory CTL. However,
      how CD4+ T cells instruct or support memory CTL during priming phase has not been
      resolved in detail. Therefore, we examined the helper function of CD4+ T cells in
      CTL differentiation. Peptide-25 is the major T cell epitope of Ag85B of
      Mycobacterium tuberculosis. We found that this peptide induced the expression of
      T-bet and TATA box binding protein-associated factor that can induce the
      chromatin remodeling of ifn-gamma gene, and as a result induced Th1
      differentiation even in the absence of IFN-gamma and IL-12. Next, we established
      an in vitro CTL differentiation system using Peptide-25, Peptide-25 specific CD4+
      T cells, OVA specific CD8+ T cells and splenic DC. By using this system, we found
      that CD4+ T cells activated DC even in the absence of IFN-gamma and CD40 ligand
      association, and the activated DC induced the functional differentiation of CTL.
      To identify the regulatory factors for DC activation, we analyzed the gene
      expression profile of helper CD4 T cells and identified 27 genes. Taken together,
      these results suggest that the inducing factors for Th1 differentiation are not
      indispensable to induce the functional differentiation of CTL.

PMID- 24579459
TI  - [Molecular mechanisms of dormancy and drug tolerance in mycobacteria].
AB  - Instead of rapid multiplication, pathogenic mycobacteria, such as Mycobacterium
      tuberculosis are likely to have acquired slow but long life. Host immunity
      affords desirable non-competitive environment for M tuberculosis in human lungs,
      where this pathogen slowly grows or arrests growing, which avoids rapid loss of
      living places. Mycobacterial DNA-binding protein 1 (MDP1), a unique histone-like
      protein associating mycobacterial GC-rich DNA, has pivotal role in realizing such
      slow life and pathogenesis including drug tolerance to isoniazid.

PMID- 24579460
TI  - Innate and acquired immune responses to mycobacterial infections: involvement of
      IL-17A/IL-23 axis in protective immunity.
AB  - Pulmonary tuberculosis is an infectious disease caused by Mycobacterium
      tuberculosis, and continues to be a serious threat to human life. Since M.
      tuberculosis establishes intracellular parasitism in macrophages, host innate and
      acquired immune systems have to detect and enhance bactericidal activity against
      the intracellular bacteria. Understanding of interaction between pathogenic
      factors of M. tuberculosis and host is also important to understand how immune
      system copes with the pathogen. In this review, we shortly summarize the
      mechanisms how innate and acquired immunity recognize M. tuberculosis or M.
      tuberculosis-infected cells and protects hosts from the infection. Furthermore,
      IL-17A/IL-23 axis, a recently focused inflammatory cytokine system, is discussed
      in the context of anti-mycobacterial protective immunity.

PMID- 24579461
TI  - [Present state of Hansen's disease between 2012 and 2013--weekly epidemiological
      record, no. 35, 2013, 88, 365-380 (translated by Shuichi Mori)].

PMID- 24579462
TI  - [Guidelines for the treatment of Hansen's disease in Japan (third edition)].
AB  - ad hoc committee of Japanese Leprosy Association recommends revised standard
      treatment protocol of leprosy in Japan, which is a modification of World Health
      Organization's multidrug therapy (WHO/MDT, 2010). For paucibacillary (PB)
      leprosy, 6 months treatment by rifampicin and dapsone (MDT/PB) is enough.
      However, for high bacterial load multibacillary (MB) leprosy, 12 months treatment
      seems insufficient. Thus, (A) For MB with bacterial index (BI) > 3 before
      treatment, 2 years treatment by rifampicin, dapsone and clofazimine (MDT/MB) is
      necessary. When BI becomes negative and active lesion is lost within 2 years, no
      maintenance therapy is necessary. When BI is still positive, one year of MDT/MB
      is added (3 years in total), followed by maintenance therapy by dapsone and
      clofazimine until BI negativity and loss of active lesions. (B) For MB with BI <
      3 or fresh MB (less than 6 months after the onset of the disease) with BI > 3, 1
      year treatment by MDT/MB is necessary. When BI becomes negative and active lesion
      is lost within one year, no maintenance therapy is necessary. When BI is still
      positive or active lesion is remaining, additional therapy with MDT/MB for one
      more year is recommended. Brief summary of diagnosis, purpose of therapy,
      character of drugs, and prevention of deformity is also described.

PMID- 24579464
TI  - [Serum GP73 were increased in patients with fatty liver disease].
AB  - OBJECTIVE: To explore the levels of serum GP73 in patients with fatty liver
      disease. METHODS: The sera GP73 were determined by ELISA in 178 patients with
      fatty liver disease and 100 healthy controls. RESULTS: Serum GP73 levels were
      significantly increased in patients with various fatty liver diseases(70.62 +/-
      60.60 ng/ml), compared with those of control population (35.61 +/- 12.22 ng/ml).
      In patients with alcoholic fatty liver disease, acute liver injury, chronic
      hepatitis B, and non-alcoholic fatty liver disease, their serum GP73
      concentration were 81.86 +/- 47.82 ng/ml, 82.77 +/- 77.73 ng/ml, 63.84 +/- 50.62
      ng/ml, and 65.75 +/- 62.20 ng/ml, respectively. But no significant difference was
      found between these groups (P > 0.05). In 68 patients with F > or = 1.0 (71.46 +/
      66.48 ng/ml), 75 patients with F> or = 2.0 (69.58 +/- 62.31 ng/ml), and 34
      patients with F3-F4 (71.65 +/- 43.89 ng/ml), there were also no marked
      differences was observed between these fatty groups (F = 0.02, P = 0.98).
      CONCLUSION: Serum GP73 levels were increased in patients with different liver
      diseases, but its concentrations were seems not related with degree of fatty
      injury.

PMID- 24579463
TI  - [The study of the expression of TCR BV CDR3 family in fulminant hepatitis B
      patients].
AB  - OBJECTIVE: To study the expression of TCR BV CDR3 family in fulminant hepatitis B
      (FHB) patients. METHODS: Totally 28 patients with fulminant hepatitis B (FHB)
      (FHB group), who were treated in our hospital from Oct. 2010. to Mar. 2012, and
      20 healthy controls( HC group) were included in the study. PBMCs were isolated
      from anticogulated blood, and RT-PCR was used to detect the levels of TCR BV CDR3
      family in the 2 groups. RESULTS: The levels of DeltaCt1, DeltaCt12 and DeltaCt20
      in FHB group were higher than those in HC group (P < 0.05); The levels of
      DeltaCt5, DeltaCt7, DeltaCt13, DeltaCt14, DeltaCt15, DeltaCt22, DeltaCt23 in FHB
      group were lower than those in HC group (P < 0.05). CONCLUSIONS: The result
      indicates that cellular immunology is involved in the pathogenesis of the liver
      inflammation process of FHB.

PMID- 24579465
TI  - [Interleukin-32 expression in serum of patients with HBV-related liver failure
      and its significance].
AB  - OBJECTIVE: To investigate the expression level of IL-32 in serum and its
      correlation with serum biochemical indices of liver function test and HBV DNA
      load in patients with HBV-related liver failure. METHODS: Fifty-five patients
      with HBV-related liver failure (severe hepatitis group) and twenty normal cases
      (control group) were enrolled in the study. Total RNA in PBMCs was extracted by
      using TRIzol. IL-32 mRNA level was assayed by using Real-time PCR. IL-32 protein
      level in serum was detected by ELSIA method. The correlation between IL-32 and
      ALT, AST, TBIL, HBV DNA load was analyzed using pearson's correlation analysis,
      respectively. RESULTS: Serum IL-32 expression level in severe hepatitis group was
      higher than that of control group. Moreover, the difference between them was
      statistically significant (P < 0.05). Serum IL-32 level was positively correlated
      with serum ALT, AST, TBIL, respectively (P < 0.05), but was not correlated with
      HBV DNA load (P > 0.05). CONCLUSION: Serum IL-32 expression level was increased
      in patients with HBV-related liver failure and was associated with the severity
      of inflammation. We, therefore, believe that IL-32 might be involved in the
      pathogenesis of HBV-related liver failure.

PMID- 24579466
TI  - [Research of the relationship of ubiquinone and beclin-1 and liver mitochondria].
AB  - OBJECTIVE: To study whether CO-Q10 can protect liver injury caused by acute on
      chronic liver failure (ACLF) by autophagy. METHODS: Rats were separated into
      three groups: control group, acute on chronic liver failure (ACLF) and
      intervenient group, liver tissues were observed by optical microscopy and
      electron microscopy. The levels of Beclin-1 expression were determined by real
      time PCR. And Western Blot. RESULTS: Areas of necrosis detected in intervenient
      group were alleviated than in ACLF significantly. Most mitochondrias had been
      degradated in ACLF group while alive in intervenient group. Real-time PCR and
      Western Blot revealed level of beclin-1 in ACLF was lower than control and
      intervenient group. CONCLUSION: Intervenient group may ameliorate rat liver
      injury by promoting autophagy.

PMID- 24579467
TI  - [Molecular epidemiological study of measles viruses isolated in Qinghai Province
      during 2000-2011].
AB  - OBJECTIVE: To carry out the molecular epidemiological study of the wild-type
      measles virus isolated in Qinghai Province during 2000-2011, and provide a
      scientific basis for the measles elimination. METHODS: Measles viruses were
      isolated using B95a cell line or Vero/SLAM cell line from throat swabs collected
      from suspected measles cases during measles outbreak and sporadic in 6
      prefectures during 2000-2011. The fragment of 696 nucleotides of N gene carboxy
      terminal was amplified by using RT-PCR methods. The PCR products were sequenced
      and analyzed. The phylogenetic tree was conducted with the viruses isolated in
      viruses from other province. RESULTS: Total 19 measles viruses were isolated
      during 2000-2011 in Qinghai province and all belong to genotype H1a. The results
      of phylogenetic tree showed that viruses in 2000-2005 and in 2009-2011 were
      distributed in two different lineages, and it revealed that these strains
      belonged to at least 2 viral transmission chains and the viruses circulated
      during 2000-2005 were not detected after 2005. CONCLUSION: Genotype H1a was the
      predominant genotype circulated in Qinghai province during 2000-2011. Qinghai
      measles virus strains had not evolved independently, but coevolved with the
      measles virus strains in other provinces in mainland China. The variation of
      important amino acid sites of measles virus should be continuous monitored and
      provide the scientific strategy for the measles elimination.

PMID- 24579468
TI  - [Epidemic situation and surveillance on SFTS in China, 2011-2012].
AB  - OBJECTIVE: To analyze the data of surveillance on severe fever with
      thrombocytopenia syndrome (SFTS), from 2011 to 2012 in China. METHODS:
      Descriptive methods were conducted to analyze the surveillance data from 2011 to
      2012 which were collected from the internet-based National Notifiable Disease
      Reporting System. RESULTS: From 2011 to 2012, a total of 1229 SFTS cases and 107
      deaths were reported in China with the average annual incidence rate of 0.
      046/100 000 and case fatality rate of 8.7%. Compared to 2011, morbidity of 2012
      has increased by 23.5% and mortality has decreased by 32%. 16 provinces reported
      SFTS cases. More cases occurred in spring and summer seasons,with the peak in May
      to July, during this period, 69% of the total cases were reported. The ages of
      the patients ranged from 1 to 85 years, 44.2% of total case was 55 to 70 years
      old, there were no differences in sex. Of all the cases 86. 8% was farmer.
      CONCLUSION: Severe fever with thrombocytopenia syndrome in widely distributed in
      China, especially in the central and eastern regions, the incidence has obvious
      seasonal. Surveillance and immigration quarantine should be strengthened.

PMID- 24579469
TI  - [The effects of recombinant human beta-defensin-3 on expression of interleukin
      17A and interleukin-22 in BEAS-2B cell].
AB  - OBJECTIVE: To research the effects of recombinant human beta-defensin-3 (hBD-3)
      on expression of interleukin-17A (IL-17A) and interleukin-22 (IL-22) in BEAS-2B
      cell. METHODS: The BEAS-2B cells were stimulated with different concentrations of
      hBD-3 for 6 hours and 24 hours, respectively. Toll-like receptor 2 (TLR2), IL-17A
      and IL-22 mRNA expression levels were determined by real-time PCR, and the
      expression levels of IL-17A and IL-22 protein were examined by enzyme linked
      immune-sorbent assay. RESULTS: TLR2 mRNA in BEAS-2B cells were significantly
      increased in a concentration-and time-dependent manner after stimulating by hBD-3
      for 24 hours compared to 6 hours. The IL-17A has significantly increased in mRNA
      and protein levels stimulated 24 hours in a concentration of 100 ng/ml, however,
      IL-17A mRNA expression has increased while protein didn't change stimulated 6
      hours in a concentration of 50 ng/ml. The IL-22 mRNA and protein expression
      reached peak levels after stimulating in a concentration of 50 ng/ml of hBD-3
      while IL-22 expression declined in mRNA and protein levels as the concentration
      of hBD-3 increased. CONCLUSIONS: Recombinant hBD-3 can up-regulated the
      expression of TLR2, IL-17A and IL-22, lower concentration of hBD-3 mainly
      increased the expression of IL-22 while higher concentration of hBD-3 mainly
      increased the expression of IL-17A. These results show that different
      concentrations of hBD-3 maybe activate different transcription factors which was
      mediated by TLR2, initiating host immune response.

PMID- 24579470
TI  - [Identification and characterization of enterovirus 71 isolated in Yunnan
      province].
AB  - OBJECTIVE: Identification and characterization of eight enterovirus 71 samples
      isolated from Yunnan province. METHODS: Collecting specimens from cases of Hand,
      Foot and Mouth Disease (HFMD), samples were identificated by RT-PCR, isolated the
      virus with cells. The isolating virus passaged in vero cells, and the vpl genes
      sequencing. Immunization the mice with the virus, neutralization test and cross
      protection test were conducted with those antisera. RESULT: All samples were
      identified as EV71, and eight strains had cytopathic effect (CPE) in vero cells,
      some antisera titers were more than 1:10,000. CONCLUSION: Eight strains of the
      virus grow well in vero cell, antiserum showed protection against EV71 A and C4
      genotype.

PMID- 24579472
TI  - [Comparative study on the clinical characteristics of HBV infection patients with
      different pathologic inflammation grade].
AB  - OBJECTIVE: The aim of this study was to compare the biochemical and virological
      characteristics among patients infected with hepatitis B virus (HBV) according to
      pathologic inflammation grade. METHODS: 428 patients with chronic HBV infection
      accept liver biopsy, liver function test, HBeAg detection and HBV DNA levels
      detection. They were studied and subdivided into four groups according to
      pathologic inflammation grade. The biochemical and virological characteristics
      were studied. Univariate analysis was performed with the SPSS 16.0. RESULTS: In
      different inflammation grading group, mean age and sex composition were no
      difference. Serum levels of ALT was highest in group G3 and lowet in group G0-1,
      there was statistically significant among groups (P = 0.005); AST and TBil were
      all highest in group G4 and lowest in group G0-1, statistically significant also
      found among groups (P = 0.000 & 0.004). Serum levels of ALB and PTA were all
      highest in group G0-1 and lowest in group G4, had statistically significant among
      groups (P = 0.000 & 0.000). There was no difference of HBV DNA level and
      percentage of HBeAg (+) among four groups (P = 0.565 & 0.065). CONCLUSIONS: The
      serum AST, TBil, ALB and PTA were different and can partly reflect the
      inflammation degree of liver damage in patients with HBV infection. ALT and PTA
      can reflect the inflammation degree of G0-1, G2 and G3; AST, TBil, ALB and PTA
      reflect the G3 and G4. HBV DNA level and HBeAg status can not indicate the
      inflammation degree in HBV infection patients.

PMID- 24579471
TI  - [Study on the etiology of acute hepatitis hospitalized patients in Beijing Ditan
      Hospital from 2002 to 2011].
AB  - OBJECTIVE: To explore the etiology of acute hepatitis hospitalized patients in
      Beijing Ditan Hospital from 2002 to 2011. METHODS: We summed up the changes in
      the characteristics of the etiology of acute hepatitis of patients mentioned
      above, and preliminarily analyze the causes. RESULTS: From 2002 to 2011, 6235
      patients with acute hepatitis were admitted to Ditan Hospital, aged between 12
      and 78 years old, Of which 4309 were male and 1926 female. Acute viral hepatitis
      accounted for 70.44%-85.07%, while CMV, EBV, drug-induced liver injury accounted
      less than 5%, and acute hepatitis D and acute hepatitis C less than 1.10%. From
      year to year, the incidence and constitution of acute hepatitis changed
      significantly. The proportion of patients with acute hepatitis in total
      hospitalized patients was from 20. 38% to 2.05%. In 10 years, the percentage of
      acute hepatitis A decreased most obviously, about 99.11%, while 45.07% decline in
      incidence of acute hepatitis B and 62. 28% of acute hepatitis E. The constituent
      ratio of acute hepatitis also changed significantly. The proportion of acute
      hepatitis A declined from 31.31% in 2002, to less than 1% in 2011. The proportion
      of acute hepatitis B increased from 26.47% in 2002 to 45.88% in 2011, an increase
      of about 2 folds in 10 years. The proportion of acute hepatitis E increased from
      26.73% in 2002 to 32.05% in 2010, a rise of 1.20 times in 10 years. CONCLUSIONS:
      The proportion of patients with acute hepatitis in total hospitalized patients
      decreased from 20. 38% in 2002 to 2. 05% in 2011 in Beijing Ditan Hospital. The
      constituent ratio of acute hepatitis changed, too.

PMID- 24579474
TI  - [Clinical trial on the prevention of diarrhea by oral BIFICO for infants aged 1-6
      years].
AB  - OBJECTIVE: To investigate the prevention of diarrhea by oral BIFICO for infants
      aged 1-6 years. METHODS: 490 cases of infants were randomly divided after age
      stratification: the experimental group (n = 247) and the control group (n = 243).
      Based on principles of randomized double-blind and placebo-controlled, the
      infants were given BIFICO (dedicated clinical research)therapy for 4 consecutive
      days, then observed for 21 days. 25 days composed a cycle. They were observed
      total 5 cycles. During the study period, principles for "the diarrhoea patients
      must be detected", follow-up visited the participant infants and conducted
      etiology detection by way of sampling for diarrhea infants. Evaluate the
      prevention efficacy of diarrhea by oral BIFICO for infants aged 1-6 years.
      RESULTS: A total of 480 completed all study. 120 and 95 infants in the control
      group and experimental group were detected with diarrhea. The incidence of
      diarrhea was 50.85% and 38.93% in these two guoup, respectively. The difference
      has statistical significance (chi2 = 4.175, P = 0.041). In the third observation
      period, the infants in the control group had a higer incidence of diarrhea
      compared with which in the experimental group (chi2 = 4.415, P = 0.036). 14
      strains of rotavirus, 3 strains of norovirus, 3 strains of sappovirus, 2 strains
      of adenovirus, 5 strains of salmonella and 4 strains of Shigella were check out
      in 128 samples. CONCLUSION: Oral BIFICO can paly certain preventive role on
      diarrhea, and decrease the incidence of diarrhea in infants aged 1-6 years.

PMID- 24579473
TI  - [Value assessment of high-risk HPV test and TCT in the screening of cervical
      carcinoma].
AB  - OBJECTIVE: To estimate the status of coincidence of high-risk HPV (HR-HPV) test
      and thinprep cytology test(TCT) with biopsy histopathological diagnosis. And
      explore the diagnostic value in the cervical cancer and precancerous lesions by
      combination of these two methods. METHODS: Retrospective analysis cases with the
      positive cytological diagnosis. Acrodding to the principle of voluntariness and
      informed consent, 3197 cases were selected and further investigated by high-risk
      human papillomavirus testing and biopsy histopathological diagnosis. We had a
      comparative analysis to the coincidence of TCT, high-risk HPV-DNA test and biopsy
      histopathological diagnosis. RESULTS: Among 3197 cases, 58.6% cases with chronic
      inflammation, 26.1% cases with condyloma or CIN I, 14.1% cases with CIN II-III,
      and 1.2% cases with invasive cervical carcinoma. Compared with pathological
      biopsy, the coincident rate of the diagnosis of TCT cytology and histopathology
      were 21.2% (ASC-US), 28.6% (ASC-H), 39.6% (LSIL), 56.2% (HSIL) and 72.4%
      (cervical carcinoma), respectively. Among cases of positive TCT diagnosis,
      Compared HR-HPV test and histopathological diagnosis, infection rate of HR-HPV
      increases significantly with increasing pathological grade (chi2 = 292.354, P =
      0.000 < 0.05). As the TCT diagnostic level increases, the positive rate of HR-HPV
      marked grows (chi2 = 144.113, P = 0.000 < 0.05). CONCLUSION: TCT can reduce the
      incidence of cancer effectively. But lower sensitivity in the low-grade cervical
      lesions may cause missed diagnosis. Combined TCT and HR-HPV test will improve the
      detection rate of cervical lesions; it is an ideal method to screening cervical
      cancer.

PMID- 24579475
TI  - [The clinical significance of hepatitis B virus large surface protein in the
      diagnosis and treatment of patients with hepatitis B].
AB  - OBJECTIVE: To explore the sigificance of HBV-LP in the HBV replication and anti
      virus treatment efficacy assessment by detect the serum HBV-LP and HBV DNA and
      Pre-S1 and HBV serum markers. METHODS: Serum HBV-LP, Pre-S1 and HBV serologic
      markers were measured by enzyme-linked immunosobent assay(ELISA), fluorescent PCR
      method to detect serum HBV DNA content in the 220 cases infected serum of CHB.
      Treated with adefovir dipivoxil antiviral therapy, and mesured the setologic
      indicators after 12 weeks, 24 weeks,36 weeks and 48 weeks. RESULTS: The detection
      rate of HBV-LP and HBV DNA detection rate no significant difference in patients
      with chronic hepatitis B, and significantly higher than the Pre-S1 and HBeAg
      detection rate. HBV-LP positive rate also similar to the HBV DNA positive rate in
      HBeAg negative CHB patients. In the anti-virus therapy, the declined of HBV-LP
      similar to HBV DNA. CONCLUSIONS: HBV-LP can reflect the HBV replication, is a
      good chronic hepatitis B diagnosis and efficacy evaluation index.

PMID- 24579476
TI  - [Relationship between effect of lamivudine in the treatment of cirrhotic patients
      with uncompensated hepatitis B with HBV genotypes and cytotoxic T lymphocyte].
AB  - OBJECTIVE: To explore relationship between effect of Lamivudine in the treatment
      of cirrhotic patients with uncompensated hepatitis B with hepatitis B virus
      (HBV)genotypes and HBV specific cytotoxic T lymphocytes (CTL). METHODS: 80 cases
      of uncompensated cirrhotic hepatitis B (40 cases with genotype B and 40 with
      genotype C), HBV DNA positive, HBeAg positive and human leukocyte antigen (HLA)
      A2 positive,were treated with Lamivudine 100 mg/d, one year later, its effect and
      relationship with HBV genotypes and HBV specific CTL were observed. RESULTS: HBV
      DNA turned negative:40 cases with genotype B turned negative (100%). In the 9th
      and 10th month of treatment, there was one case with genotype C had YMDD
      variation respectively and Adefovir dipivoxil was used for treatment, of the rest
      38 cases, HBV DNA of 26 cases (68.42%) turned negative,HBV DNA negative rate of
      patients with genotype is lower than that of patients with genotype B, chi2 =
      14.91, P < 0.01. HBeAg turned negative: 18 cases with genotype B (45%) turned
      negative, more than that of patients with genotype C (7 cases, 18.42%), chi2 =
      6.32, P < 0.05. Peripheral blood HBV specific CTL level: before treatment, it was
      (0.33 +/- 0.03)% of patients with genotype B,higher than that of patients with
      genotype C [(0.11 +/- 0.02)%], t = 8.12, P < 0.001. 1 year after treatment: it
      was (0.44 +/- 0.04)% of patients with genotype B, higher than that before
      treatment, t = 4.01, P < 0.001, it was also higher than that of patients with
      genotype C 1 year after treatment [(0.23 +/- 0.03)%], t = 5.63, P < 0.01, alanine
      amino-transferase (ALT) returned to normal: 38 cases with genotype B (95%)
      returned to normal, more than that of patients with genotype C (28 cases,
      73.68%), X2 = 6.79, P < 0.01. CONCLUSION: Effect of Lamivudinein the treatment of
      cirrhotic patients with uncompensated hepatitis B is better in patients with
      genotype B than patients with genotype C, its mechanism may be related to lower
      level of HBV specific CTL in patients with genotype C than patients with genotype
      B.

PMID- 24579477
TI  - [To investigate the opportunity of entecavir treatment for HBeAg-negative acute
      on-chronic liver].
AB  - OBJECTIVE: To explore relations between the opportunities and effects of internal
      general treatment added Entecavir on acute-on-chronic liver failure (ACLF) of
      HBeAg-negative chronic hepatitis B in different score ranges of acute-on-chronic
      liver failure severity. METHODS: A total of 108 ACLF of HBeAg-negative chronic
      hepatitis B patients with different ACLF severity score were treated with
      internal general treatment added Entecavir. The liver failure severity scores,
      HBV-DNA loads during the initiation of therapy, recovery phase and in deathbed
      phase, courses of Entecavir administration and mortalities were studied. RESULTS:
      For 19 patients with high ACLF score (> or = 12), the difference in ACLF score
      between pre and post-treatment was not significant. The difference in HBV-DNA
      load between pre and post-treatment was not significant and the mortality was
      18/19. For 30 patients with higher intermediate ACLF score (8-11), the difference
      in ACLF score between pre and post-treatment was not significant. The difference
      in HBV-DNA load between pre and post-treatment was significant, and the mortality
      was 66.67% (20/30). For 36 patients with lower intermediate ACLF score (5-7), the
      difference in ACLF score between pre and posttreatment was not significant. The
      difference in HBV-DNA load between pre and post-treatment was significant, and
      the mortality was 30.56% (11/36). For 23 patients with low ACLF score (< or = 4),
      the difference in ACLF score between pre and post-treatment was significant. The
      difference in HBV-DNA load between pre and post-treatment was significant, and
      the mortality was 8.70% (2/23). CONCLUSIONS: A novel acute-on-chronic liver
      failure scoring system can syllabify differentiate the relations between the
      opportunities and efficacies on the Entecavir treatment for HBeAg-negative ACLF.

PMID- 24579478
TI  - [Construction of recombinant CHO cell strain for high expression of HBsAg].
AB  - OBJECTIVE: To overexpress hepatitis B virus S gene in CHO cells cultured in serum
      free media. METHOD: Plasmid was constructed by cloning of HBV S gene and then it
      was transfected into CHO cells. After cell screen, the positive clones were
      identified and isolated into a serum-free media followed by the serological and
      morphological characterization of the expression product. RESULT: CHO cell
      strains which can express HBsAg efficiently and stably were obtained. Spherical
      and filamentous HBsAg could be detected under electronic microscope. The titer of
      the expression product was up to 1:5000. CONCLUSION: Serum-free media cultured
      CHO cell strain for overexpression of HBsAg was successfully constructed and the
      expression product was high antigenic.

PMID- 24579479
TI  - [Establishment of a detection method for hepatitis B virus large surface protein
      (HBV-lP)].
AB  - OBJECTIVE: To establish enzyme-linked immunosorbent assay (ELISA) for detection
      of hepatitis B virus large surface protein(HBV-LP) in serum. METHODS: A sandwich
      reaction was preformed with horseradish peroxidase labeled monoclonal antibody of
      HBV-LP as the catalytic enzyme. Several reactions liquid's concentration and
      reaction conditions were optimized. The method was evaluated in all aspects such
      as sensitivity, specificity, stability and so on. RESULTS: The detection limit
      was 5 ng/ml. Interassay and intra-assay RSD were both less than 10%. After stored
      at 4 degrees C and 37 degrees C for 3, 5, 7 days, the analysis showed correlation
      coefficient higher than 0.98 and RSD lower than 10%. CONCLUSION: Established
      ELISA for determination of serum HBV-LP has high sensitivity and repeatability.
      Enzyme-linked immunosorbent assay;

PMID- 24579481
TI  - [Microplate chemiluminescence enzyme immunoassay for the quantitative analysis of
      tissue inhibitor of metalloproteinases I].
AB  - OBJECTIVE: To establish microplate chemiluminescence enzyme immunoassay (CLEIA)
      for quantitative analysis of tissue inhibitor of metalloproteinases I (TIMP I) in
      human serum. METHODS: A sandwich reaction was preformed with horseradish
      peroxidase(HRP) labeled monoclonal antibody of TIMP I as the catalytic enzyme and
      the H2O2-luminol as the luminescence reagent. Several physical and chemical
      parameters were studied and optimized such as immunoreaction conditions, the
      dilution ratio of TIMP I-HRP, luminescence reaction time and so on. In order to
      evaluate the method, recovery test, heat stabilization test and comparison test
      were carried out. RESULTS: The linear range was 0. 2-12 ng/ml with r = 0.996. The
      detection limit was 0.12 ng/ml. Inter-assay and intra-assay RSD were both less
      than 10%. The recoveries of three different spiked concentration samples were
      100.6%, 96.5% and 106.5%. After stored at 4 degrees C and 37 degrees C for 3, 5,
      7 days, the analysis showed correlation coefficient higher than 0. 998 and RSD
      lower than 6%. The detected results with CLEIA closely corresponded to those with
      imported ELISA in 60 patients sera with liver fibrosis. CONCLUSION: Established
      CLEIA for quantity determination of serum TIMP I has high accuracy, sensitivity
      and repeatability.

PMID- 24579480
TI  - [Expression and bioassay of rubella virus E1-374 glycoprotein in yeast cells].
AB  - OBJECTIVE: To express the rubella virus E1-374 glycoprotein in Pichia pastoris
      and study the immunogenecity of the recombinant protein. METHODS: The cDNA of
      protein E1-374 was cloned into the expression vector pGAPZalphaA and transformed
      into Pichia pastoris GS115 cells by electrotransfection. The expressed protein
      was confirmed by indirect immunofluorescence and demonstrated immunoreactivity by
      Western Blot. Rubella virus IgG antibody was assayed with ELISA after mice were
      inmmunized by E1-374 glycoprotein. RESULTS: SDS-PAGE analysis and Western Blot
      analysis of E1-374 protein revealed this protein to be 46.89 x 10(3). Antiserum
      (1:100) and E1-374 (5.5 microg/ml) was chosen for ELISA optimization. The intra
      assay coefficient of variation for the ELISA was 0.36%-12.45%. CONCLUSION:
      Protein E1-374 was highly expressed in Pichia pastoris cells, and it was a good
      choice to prepare rubella virus recombinant protein vaccines.

PMID- 24579483
TI  - [Comparison of two kinds of enzyme-linked immunosorbnent assay for detection of
      anti-hepatitis C].
AB  - OBJECTIVE: To compare the difference of sensitivity and specificity on the
      results of the same samples determined by indirect ELISA and sandwich ELISA.
      METHODS: A 51 anti-HCV positive serum samples obtained from donors were screened
      by two indirect ELISA kits initially, and then were detected using one sandwich
      ELISA kit, and were confirmed by recombinent immunoblot assay (RIBA) and HCV-RNA.
      RESULTS: To compared with HCV-RNA, false positive rate of two kinds of indirect
      ELISA and one sandwich ELISA was 40.9%, 59.1% and 2.2% respectively. The positive
      rates of them were 100%, but the analytical sensitivity of sandwich ELISA was
      more than indirect ELISA 2 to 6 times. CONCLUSIONS: The sensitivity and
      specificity of sandwich ELISA was significantly better than those of indirect
      ELISA.

PMID- 24579482
TI  - [Cloning and expressing of golgi protein73 gene fragment and preparation of
      monoclonal antibodies against the recombinant protein].
AB  - OBJECTIVE: To clone and express human Golgi glycoprotein73 protein, and prepare
      the monoclonal antibody (mAb) against the protein. METHODS: GP73 gene was
      amplified from HepG2 cells by RT-PCR, then ligated with pQE31 to form recombinant
      plasmid pQE-GP73 and transformed into E. coli BL21. The protein induced by IPTG
      was purified by 6 x His-tag and used to immunize the BALB/c mice. The specific
      monoclonal antibodies (mAbs) were prepared by the cell fusion technique. Western
      Blot was used to detect specificity of mAbs. RESULTS: The prokaryotic plasmid
      expressing the recombinant protein was constructed, and the GP73 recombinant
      protein was expressed and purified. Five hybridoma cell lines that secreted anti
      GP73 mAbs were obtained. 2 of 5 mAbs were the IgG1 subtype. Western Blot
      indicated the mAbs showed specific combination with GP73 protein. CONCLUSION: The
      GP73 recombinant protein is highly purified and has strong antigenicity. The anti
      GP73 mAbs were prepared successfully.

PMID- 24579484
TI  - [Performance evaluation of TP antibody detection by CLIA kits made (in China)
      domestically].
AB  - OBJECTIVE: To analyze the clinical performance of TP antibody detection by CLIA
      kits and evaluate whether the CLIA kits made in China is suitable for clinical
      use. METHODS: 1200 samples were collected from Beijing Hospital including 300
      samples with confirmed TP infection and 900 healthy control samples. To detect
      the TP antibody of the 1200 sanples separately by the CLIA kits and the ELISA
      kits at the same time. The test results were analyzed with statistical methods.
      RESULTS: The sensitivity and specificity of the CLIA kits were 99.3% and 99.9%
      respectively, and positive predictive value of 99.7%, negative predictive value
      of 100%. With the ELISA method, the positive coincidence rate was 98.7%, the
      negative coincidence rate was 99.8%, and the total coincidence rate was 99.5%.
      CONCLUSION: The CLIA kits showed good clinical performance and the agreement rate
      with the ELISA kits was. The CLIA kits are suitable for clinical use.

PMID- 24579486
TI  - Prospective evaluation of the impact of daycare attendance on the prevalence of
      otitis media with effusion in 6 to 24 months old children in urban Nigeria.
AB  - BACKGROUND: The peak age prevalence of otitis media with effusion (OME) is in
      early childhood. Day care attendance has been established by various studies as a
      risk factor for the development of OME. OBJECTIVE: This study is aimed at
      evaluating the prevalence of OME among children aged 6 - 24 months, and the
      impact of day care center (DCCs) attendance on the OME occurrence. METHODS: A
      prospective cohort study conducted in children recruited from DCCs and
      immunization clinics in Surulere, Lagos state, Nigeria. They were matched mainly
      on their place of care, at home or at day care center and presence or absence of
      OME using pneumatic otoscopy and tympanometry. RESULTS: A total of 152 children
      were studied. Based on their place of care, they were divided into day care
      attendees 64 (42.1%), and non day care attendees 88 (57.9%). The prevalence of
      OME was 37.7% overall, 43.7% in the day care attendees and 33.4% in the non day
      care attendees. Factors found to positively influence the prevalence of OME in
      this study include: young age 6-12 months, female gender and day care attendance.
      CONCLUSION: OME is common in Nigerian children at young age. Day care facility
      attendance significantly increased OME prevalence.

PMID- 24579485
TI  - Overview of dermatophyte infections at the dermatology outpatient clinic of a
      tertiary institution in Nigeria.
AB  - BACKGROUND: Dermatophytes are the commonest organisms causing superficial fungal
      infections. Earlier epidemiologic studies in Nigeria revealed dermatophyte
      infection as one of the top three reasons for visiting the dermatologists.
      OBJECTIVE: To determine the frequency, characteristics and predisposing factors
      to dermatophyte infections at the dermatology outpatient clinic of the Lagos
      University Teaching Hospital (LUTH) from March 2003 to September 2009. METHODS:
      The clinic records and case notes of patients were reviewed. Patients' data which
      includes demographic details, characteristics of disease, predisposing factors
      and clinical presentation findings were entered on Excel spreadsheets and
      analyzed using SPSS 15. Results were displayed using frequency tables. RESULTS:
      Dermatophyte infections were found in 8.39% of patients attending the dermatology
      outpatient clinic of LUTH. Tinea pedis was the most frequently seen, occurring in
      33.6% of patients; followed by tinea corporis (20%), tinea manuum (18.6%) and
      tinea capitis (14.8%). Dermatophyte infection was most frequently seen in the 3rd
      and the 4th decades of life, except tinea capitis seen predominantly in the 1st
      decade of life and tinea intertrigo in the 5th decade. CONCLUSION: Dermatophyte
      infections occur at all age groups, although frequency of occurrence differs with
      age group and site of the body affected.

PMID- 24579487
TI  - Prescribing of antidiabetic medicines to older diabetes type 2 patients in Lagos,
      Nigeria.
AB  - BACKGROUND: The incidence of diabetes mellitus in older adults is increasing in
      Lagos and other parts of Nigeria but there is paucity of information on the use
      of medicines in this group of patients. OBJECTIVE: A survey was therefore carried
      out to determine the prevalence of potentially inappropriate prescribing of
      antidiabetic medications to older diabetes adults in Lagos, Nigeria. METHODS: A
      convenient sample of physicians working in seven health care facilities in Lagos
      were surveyed using a self-administered pre-tested questionnaire to determine the
      medications they often prescribed for diabetes patients older than 50 years,
      whether they consider dosage reduction in these patients, and the counselling
      information they provide to the patients. AGS 2012 Beer's criteria were used to
      determine potentially inappropriate medication (PIM) for the patients. Factors
      associated with the tendency to prescribe inappropriately were then evaluated
      using logistic regression analyses. RESULTS: Glibenclamide, metformin, and
      metformin/glimepiride combination were regularly prescribed by 45.64-87.25% of
      the physicians but gliclazide, pioglitazone, pioglitazone/metformin and
      pioglitazone/glimepiride combinations were prescribed occasionally by 41.61
      61.74% of them. Majority of the physicians (87.25%) prescribe glibenclamide to
      the older patients and do not also always consider dosage reduction on account of
      older age. Some of these (30.2%) of these physicians equally prescribed
      chlorpropamide to the patients. Postgraduate qualification was the only
      significant factor associated with prescription of chlorpropamide (p < 0.05).
      CONCLUSION: Inappropriate use of chlorpropamide and glibenclamide, and failure to
      consider dosage reduction on account of older age have been reported by
      physicians treating older diabetes patients in Lagos. This calls for continuous
      education of physicians in Lagos as well as in other parts of Nigeria to promote
      rational use of antidiabetic medications in the country.

PMID- 24579488
TI  - Haematotoxic and reproductive toxicity of fixed dose combined anti-tuberculous
      agents: protective role of antioxidants in rats.
AB  - BACKGROUND: Tuberculosis (TB) is the world's greatest infectious killer of women
      of reproductive age and the leading cause of death among people with HIV/AIDS.
      The major problem militating against the management of tuberculosis is the lack
      of compliance to medication by the infected patients as a result of multidrug
      needed to be taking daily leading to resistance. Occurrences of hepatic toxicity,
      teratogenicity, sperm quality damage, haematotoxicity and meningeal congestion of
      individual anti-tuberculous agents have been reported. OBJECTIVE: The study is
      aimed to determine the reproductive and haematological toxicity of combined
      antituberculous agents and the modulatory role of antioxidants using animal
      model. METHODS: Fifty rats (10 per group) were randomly allotted to five groups,
      consisting of the control, the fixed dose combined anti TB agents treated group,
      the fixed dose combined anti TB agents plus vitamin C treated group, the fixed
      dose combined anti TB agents plus vitamin E treated group and the fixed dose
      combined anti TB agents plus vitamin C plus vitamin E treated group. Therapeutic
      doses of the fixed dose combined anti TB agents (25 mg/kg/day), vitamin E (5
      mg/kg) and vitamin C (8 mg/kg) were administered to the animals via oral gavage,
      daily over 28 days. After 28days, rats were sacrificed for internal macroscopic
      and histological examination of the organs, sperm analysis and haematological
      investigations were carried out. RESULTS: The results showed a significant
      increase (p < or = 0.05) in the levels of white blood cells (WBC), red blood cell
      (RBC) and haemoglobin (HB) of the combined anti-TB plus vitamins C or E treated
      groups compared with combined anti-TB treated group alone (56.34 +/- 0.11) that
      decreased the haematological parameters. A significant decrease (p < or = 0.05)
      in the sperm counts (22.26 +/- 0.02; 35.40 +/- 0.02) and motility (77.03 +/-
      0.02; 94.50 +/- 0.01) of the combined anti-TB treated rats as compared with the
      control group were observed. The combined anti-TB plus vitamin C treated rats
      demonstrated a significant increase (p < or = 0.05) in the sperm motility (90.23
      +/- 0.01) as compared with the control group. There was also a remarkable
      decrease in the abnormal morphology of the sperm in the combined anti-TB plus
      vitamins E and C treated rats (0.05 +/- 0.02) as compared with the combined anti
      TB group alone (1.10 +/- 0.02). CONCLUSION: Vitamins C and E positively modulated
      the sperm quality and haematological damage produced by the Fixed Dose Combined
      Anti-Tuberculous agents.

PMID- 24579489
TI  - What do medical interns in Nigeria think of the white coat? A cross sectional
      study.
AB  - BACKGROUND: The appeal of the white coat to both the doctors and the public is
      waning. In most developing countries such as Nigeria doctors' view of the white
      coat is not known. OBJECTIVE: To determine the proportion of interns which
      supported wearing of white coat by doctors. METHODS: A 10-item questionnaire was
      distributed to medical interns undertaking mandatory pre-registration training in
      a tertiary hospital. Characteristics of interns who were supportive of doctors
      wearing the white coat were compared to those who did not support or were
      indifferent to it. RESULTS: Two hundred and thirty three interns returned
      completed questionnaires. About 54% (126) and 52% (107) of the participants were
      males and graduates of the College of Medicine, University of Lagos respectively.
      The majority of interns (167; 71.7%) supported the wearing of white coats by
      doctors when attending to patients; 22 (9.4%) were opposed to it while 44 (18.9%)
      were indifferent. Older interns, females and interns who had not rotated through
      Paediatrics were more likely to support the wearing of white coats by doctors.
      The commonest reason for wearing the white coat was for identification.
      CONCLUSION: The majority of medical interns supported the wearing of white coat
      by doctors. Prevention of infection is no longer the major reason for wearing the
      white coat. There is need to document the public's perception of the white coat.

PMID- 24579490
TI  - Anterior knee pain associated with an anterior superior patellar bony spur: a
      case report.
AB  - Anterior knee pain is a common presentation in Orthopaedic out patient practice.
      However anterior superior patellar spur is an uncommon cause.This case
      presentation is to highlight an anterior superior patellar spur with quadriceps
      tendonitis. The patient is a 52 year old man who presented with a recurrent
      anterior knee pain. The radiographic study revealed an anterio-superior patellar
      spur. The patient had a depo steroid injection as an adjunct therapy to
      physiotherapy and has been pain free.

PMID- 24579491
TI  - Otologic and audiological evaluation among HIV patients in Ilorin, Nigeria.
AB  - BACKGROUND: HIV infection is the highest cause of death worldwide and presenting
      eventually with ENT regions. OBJECTIVE: This study is to determine the prevalence
      of hearing loss and hearing patterns among adults Nigerians with HIV and causal
      relationships between CD4+ counts with the degree of hearing impairments.
      METHODS: This prospective study was carried out among all consecutive HIV
      positive patients attending the clinic at the University of Ilorin teaching
      hospital (U.I.T.H.), Ilorin, Nigeria between January and July, 2008. They all had
      audiological assessments with a pure tone audiometer within the frequency range
      250 to 8,000 Hz to determine their hearing thresholds together with their CD+
      counts estimations. RESULTS: 89 were evaluated in the age range of 18 to 56 years
      (Mean 36.4 years, SD of 8.82) and the modal age group was 21-39 years (59.6%), 40
      56 years (38.2%).There were 51 males (57.3%) and 38 females (42.7%) with a
      male/female ratio of 1.3:1.0. Otological symptoms included tinnitus (15.7%),
      vertigo (15.7%), otalgia (14.6%) and hard of hearing (10%). Examinations showed
      bilateral serous Otitis media (glue ear) in 58 patients (65.1%) with no
      affectation of the facial nerves. PTA showed mixed, conductive and SNHL in 32
      patients (36%), 20 patients (22.5%), 9 patients (10.1%) respectively and only
      15(16.9%) had normal hearing thresholds. The CD4+ counts ranged between 12 to
      616. CD4 counts with hearing loss mostly < 300mm3. CONCLUSION: The prevalence of
      hearing loss is 87% among HIV infected patients, mostly mixed HLwith causal
      relationships between reduced CD4+ counts of less than 300/mm3 with severity of
      hearing loss. The hearing loss can interfere with the communication and specific
      knowledge vital to the development of best practices towards ensuring the
      inclusion of hearing impaired in HIV/AIDS prevention and treatment programmes.

PMID- 24579492
TI  - Concomitant injuries associated with maxillofacial fractures in Abuja, Nigeria.
AB  - BACKGROUND: Injury is the leading cause of death and disability and the third
      most common cause of death Little attention has been given to the concomitant
      injuries associated with maxillofacial fractures in scientific literatures.
      OBJECTIVES: For effective planning and efficient management of the patients,
      there is need to study the pattern ofthese injuries. METHODS: Consecutive
      patients who sustained one or more facial bone fractures over a period of 2 years
      were prospectively studied. RESULTS: There were 103 patients out of which 96
      sustained concomitant injuries giving an incidence of 93.2%.There were 75 (78.1%)
      males and 21 (21.9%) females with a M:F of 3.6:1. The mean + (SD) age was 30.8
      +13.0 with a range of 2.0 to 68.0 years. Road Traffic Crashes was the commonest
      (n = 81, 84.4%) cause of injury. Soft tissue of the face, with an incidence of
      62.1% (n = 64) was the commonest concomitant injury. It was followed by
      neurologic injury (n = 51, 49.5%) and ophthalmic injury (n = 38, 36.9%) while
      abdominal injury (n = 2, 1.9%) was the least common. Majority (87.5%) of the
      ophthalmic injury patients sustained midfacial fracture while 12.5% of the them
      sustained mandibular fractures. Pulmonary and cervical injuries were found to be
      associated more with mandibularfractures. CONCLUSION: Concomitant injuries occur
      commonly with maxillofacial fractures and they were found to have significant
      effect on the management of the fractures. A multidisciplinary approach will
      bring about a very efficient management of patients.

PMID- 24579493
TI  - Relationship between discrepancies in upper-limb anthropometrics and
      functionality in children with obstetrical brachial plexus injury.
AB  - BACKGROUND: Children with obstetrical brachial plexus injury often present with
      relative reduction and deficit (discrepancies) in length, girth and functional
      performance in their affected upper-limb. However, the relationship between these
      discrepancies and the functional deficit is still unclear. OBJECTIVE: This study
      evaluated discrepancies in upper-limb of children with obstetrical brachial
      plexus injury, and find the relationship between these discrepancies and the
      functional performances in the affected upper-limbs. METHODS: This study involved
      50 children with obstetrical brachial plexus injury undergoing rehabilitation at
      selected secondary and tertiary health institutions in Lagos state, Nigeria.
      Upper-limb-length, arm-girth and forearm-girth were measured using broad-blade
      anthropometer and inelastic tape measure. Modified Mallet-Scale was used to
      assess functional performances of the upper-limbs while joints' range of motion
      was assessed using a full-circle goniometer. Data was analysed using Pearson's
      Correlation Coefficient, paired and independent t-test. RESULTS: Participants
      were aged 47.86 +/- 124.50 months. Discrepancies in upper-limb length and arm and
      forearm girth were 2.17 +/- 3.19 cm, 0.21 +/- 0.78 cm and 0.73 +/- 0.73 cm
      respectively. There was significant discrepancy in lengths, girths and functional
      performance between affected and unaffected upper-limb. The age of commencement
      of treatment ranged between one day and 2555 days with a mean of 2224.52 +/-
      469.30 days. Time of commencement of treatment was significantly related with
      lengths, girths and functional performance of the affected upper-limbs.
      CONCLUSION: There are significant discrepancy in lengths, girth and functional
      performance between affected and unaffected upper limb of children with
      obstetrical brachial plexus injury. There is negative significant relationship
      between time of commencement of treatments and the discrepancies that occurred in
      the affected upper-limb of children with obstetrical brachial plexus injury.

PMID- 24579494
TI  - Review of ciprofloxacin use in children.
AB  - BACKGROUND: The frequency of prescriptions for ciprofloxacin use in children is
      high despite the caution recommended. OBJECTIVE: To assess frequency of
      ciprofloxacin prescriptions in a pediatric unit and review the literature on use
      of ciprofloxacin in children. METHODS: Patient case notes in a pediatric general
      ward of a tertiary hospital were reviewed. Electronic databases were searched for
      articles published in English between January2001 and December2011. RESULTS:
      Ciprofloxacin was prescribed for 20% of the children in our preliminary study. In
      all the studies reviewed ciprofloxacin was used as a second line treatment in
      life-threatening cases and only for organisms that were susceptible on culture.
      Adverse events such as arthralgia, gastro intestinal disturbances and CNS
      reactions were recorded; they were reversible and often did not warrant
      discontinuation of therapy. CONCLUSION: Ciprofloxacin may be used in children as
      second line treatment, in life-threatening cases, for susceptible organisms when
      the benefit outweighs the risk.

PMID- 24579495
TI  - Ageratum conyzoides attenuates alcohol induced liver toxicity in male Wistar
      rats.
AB  - BACKGROUND: Ageratum conyzoides (AC) is unique for its antioxidant activity and
      protective role to tissues. However this property is yet to be demonstrated in
      animals administered toxic alcohol concentrations. OBJECTIVE: To determine the
      effect of AC extract on the oxidative stress, liver enzymes and histology.
      METHODS: Twenty four male rats (190-230 g) were divided into three groups of
      eight rats. Group A (control) administered distilled water. Group B (ethanol
      group) received 10 g/kg body weight of ethanol. Group C (ethanol + AC group) were
      treated with ethanol (as above) and AC (250 mg/kg body weight) concurrently.
      Total experimental duration was 35 days at the end of which animals were
      euthanized by cervical dislocation. Liver and blood samples were taken and
      processed for: microscopic studies, estimation of activities of liver enzymes
      [alanine aminotransferase (AST), aspartate aminotransferase (ALT) and alkaline
      phosphatase (ALP)], Malondialdehyde (MDA) and antioxidants [Superoxide dismutase
      (SOD), Glutathione peroxidase (GSH-Px) and Catalase (CAT)] respectively. RESULTS:
      Compared to control, the rats treated with ethanol had significantly increased
      liver enzymes and MDA levels but these were decreased in ethanol + AC group
      compared to the ethanol group. The histologies of concurrent ethanol + AC treated
      group were similar to control groups. CONCLUSION: AC protects the liver against
      alcohol induced damage.

PMID- 24579497
TI  - The agreement of point-of-care and standard laboratory electrolyte and glucose
      analysis in critically ill patients in a sub-Saharan tertiary teaching hospital.
AB  - BACKGROUND: The critically ill patient undergoes rapid changes in the internal
      milieu requiring quick intervention. Point of care testing has been shown to be
      valuable in the early diagnosis and management of such patients. OBJECTIVE: This
      study determined the agreement between I-STAT Abbot point of care testing with
      standard laboratory testing in the analysis of electrolytes and glucose
      concentrations in critically ill patients. METHODS: The study was performed in a
      Sub-Saharan Tertiary Teaching Hospital in critically ill patients. Electrolyte
      and glucose analysis were measured with I-STAT Abbot Analyzer unit with parallel
      blood specimens (n = 30) tested in the laboratory on an ion-selective electrode,
      SFRI analyzer ISE 6000. RESULTS: There was no significant difference in mean
      sodium, potassium, chloride and glucose between I-STAT POCT and standard
      laboratory measurements. The agreement between POCT and laboratory glucose was
      good p(c) = 0.967, mean difference of 0.79 and 95% limit of agreement from -3.83
      to +5.107 mmol/L, p = 0.733. Bicarbonate was moderate (p) = 0.637, mean
      difference of 1.95 and 95% limit of agreement from -4.294 to +0.394 mmol/L, p =
      0.101. There was moderate agreement for sodium (p(c)) = 0.32, mean difference of
      5.8 and 95% limit of agreement from -0.378 to +11.98 mmol/L, p = 0.064. Agreement
      for potassium was moderate (p(c)) = 0.439, mean difference of 0.15 and limit of
      agreement from -0.401 to +0.701 mmol/L, p = 0.588. There was, however, a
      significant difference in mean chloride, and BUN values; chloride (p(c)) =
      0.0796, mean difference of 13.8 and 95% limit of agreement from -7.55 to + 20.015
      mmol/L. Blood urea nitrogen (p(c)) = 0.064, mean difference of 18.55 and 95%
      limit of agreement from -30.126 to +6.974 mmol/L. CONCLUSION: The mean sodium,
      potassium, glucose and bicarbonate were comparable with moderate to good
      agreement between I-STAT POCT and ISE 6000 Analyzer. Though, the mean BUN and
      chloride levels between the analytical methods differ significantly.

PMID- 24579496
TI  - Analysis of film reject rate in the diagnostic x-ray facility of a tertiary
      health institution in Benin, Nigeria.
AB  - BACKGROUND: Film rejects analysis (FRA) as part of quality assurance tests in
      radiography services, is carried out periodically to identify causes of film
      rejection and to proffer solutions to ameliorate such problems. OBJECTIVE: The
      study was carried out to estimate film rejection rate in a tertiary health
      facility in Benin, Nigeria and also to identify causes of film rejection in the
      centre. METHODS: This prospective study was carried out within 6 months. Ethical
      approval was obtained from the local committee on research and ethics before the
      study commenced. Only routine x-ray procedures were included in the study. Four x
      ray rooms and four radiographers with equal training and job experience were
      selected for the study. Different boxes labeled for each room were used to daily
      collect rejected films. RESULTS: Overall rejection rate was 6.7%. Improper
      exposure caused the highest rate of repeats (> 12% in the old x-ray rooms).
      Highest rejection rates (31%) were found in the old x-ray rooms. Paranasal
      sinuses examination accounted for highest rejection rate (25%) among all routine
      x-ray investigations considered. CONCLUSION: Rejection rate found was within
      recommended limits.Obsolete but poorly maintained x-machines layed major roles in
      overall film rejection rate in the centre. X ray of paranasal sinuses was
      challenging to radiographers observed. Radiographers should embrace CPD while
      obsolete x-ray equipments found in the centre should be scrapped to further
      reduce film reject rate in the centre.

PMID- 24579498
TI  - Effect of health education on the knowledge and attitude to sickle cell disorder
      and screening practices among school of nursing students in Sokoto, Nigeria.
AB  - BACKGROUND: Sickle cell disorder is the most important genetic hematological
      disease that affects people of black African descent. The years of young
      adulthood present a good opportunity for screening and counseling for this
      genetic blood disorder. OBJECTIVES: To assess effect of health education and
      provision of free sickle cell haemoglobin screening on knowledge of sickle cell
      disorder, attitude towards sickle cell haemoglobin screening, and uptake of
      sickle cell haemoglobin screening among students of a School of Nursing. METHODS:
      Study design was a quasi-experimental noncontrolled study. Self-administered
      questionnaire was used for pre- and post-intervention data collection.
      Implemented interventions were seminar on sickle cell disorder combined with free
      sickle cell haemoglobin screening. The data was analyzed with Epi-info version
      3.5.1 statistical software package. RESULTS: Respondents who participated in all
      the study phases were 104. Mean knowledge score (%) was high (80.9 +/- 22.8%) at
      baseline and improved significantly to 91.8 +/- 9.4% (p < 0.001) at post
      intervention. 91.3% were willing to screen fiancee before getting married while
      72.1% were willing not to go ahead with marriage if self and fiancee are carriers
      of sickle cell haemoglobin. Phenotype of the respondents that volunteered to be
      screened for sickle cell haemoglobin were: A (70.5%), AC (6.8%) and AS (22.7%).
      CONCLUSIONS: Implemented interventions, seminar on sickle cell disorder combined
      with free sickle cell haemoglobin screening service yielded significant impact on
      respondents' knowledge, attitude and uptake of sickle cell haemoglobin screening.

PMID- 24579499
TI  - Emergency obstetric hysterectomy in a Nigerian teaching hospital: a ten-year
      review.
AB  - BACKGROUND: Haemorrhage is a leading cause of maternal mortality worldwide and
      hysterectomy may become necessary to save life. This procedure is associated with
      significant morbidity and mortality. OBJECTIVE: To determine the, indications,
      risk factors and the management outcome for the procedure in our unit. METHODS: A
      retrospective case controlled study of 34 cases of emergency obstetric
      hysterectomy (EOH) performed at the Lagos University Teaching Hospital over a
      period often years was carried out. RESULTS: The incidence of EOH was 2.56 per
      thousand deliveries. Increasing parity, history of previous caesarean section,
      placenta praevia and current delivery by caesarean section were significant risk
      factors for the procedure. The indications were ruptured uterus (61.8%),
      intractable haemorrhage during caesarean section (32.4%), and uterine atony
      (5.9%). Majority (73.5%) of the patients had subtotal hysterectomy but the
      outcome indices were similar for the total and subtotal procedures. The case
      fatality rate was 11.8%. Post-operative complications included anemia (100%),
      urinary tract infection (UTI) (14.7%) and wound infection (11.7%). CONCLUSION:
      The incidence of EOH in our unit has increased since the last study published in
      1983, but the associated mortality has decreased. The indications differed in
      proportion from those in developed countries although the risk factors were
      similar. The outcome indices were similar for the total and the subtotal
      procedures. EOH is still associated with considerable maternal morbidity and
      mortality which can be reduced by provision of better obstetric care for the
      population.

PMID- 24579500
TI  - Clinical evaluation of 16% and 35% carbamide peroxide as in-office vital tooth
      whitening agents.
AB  - BACKGROUND: Tooth bleaching (whitening) is a conservative and cost effective
      treatment of discoloured teeth. OBJECTIVES: The purpose of this study was to
      evaluate the clinical efficacy and safety of 16% and 35% carbamide peroxide as in
      office bleaching agents. METHODS: Thirty adult subjects who desired to whiten
      their discoloured teeth were enrolled in the study. Carbamide bleaching agents,
      in concentrations of 16% and 35%, were used to whiten their teeth employing the
      spilt-arch technique/half-mouth design using vacuum formed half-arch matrix
      seated over the maxillary teeth for a one-hour session per week for two weeks.
      Outcome was monitored with Vita shade guide and photographs. RESULTS: Twenty
      females and ten males, ages 18-43 years, with mean age 27.83 years, participated
      in the study. Tooth whitening was obtained in all subjects. Shade tab movement of
      2-4 shades and 4-6 shades was recorded at first sessions then 3-5 and 5-9 shades
      at second sessions for 16% and 35% concentrations of carbamide peroxide
      respectively. The bleaching outcome was significantly better with the 35%
      concentration of carbamide peroxide while transient tooth sensitivity was
      observed in both concentrations ofthe bleaching agents. CONCLUSION: Carbamide
      peroxide in 16% and 35% concentration are effective and safe for bleaching
      discoloured vital teeth, however, 35% concentration gave significantly more
      lightening effect without additional side effects compared to 16% concentration.

PMID- 24579501
TI  - Autopsy study of prostatic weight and lesions in LUTH: a 12 month prospective
      study.
AB  - BACKGROUND: Diseases of the prostate are common among adult Nigerians with some,
      clinically asymptomatic during life. OBJECTIVE: The study is to determine the
      prostatic weight and document the histopathologic patterns, frequency, and age
      distribution of clinically asymptomatic prostatic lesions seen at autopsy in
      LUTH, Lagos, Nigeria over a 12 month period (January to December 2009). METHODS:
      Consisted of hospital case files and prostate glands harvested en bloc from all
      autopsies in men aged 20 years and above who died of other causes other than
      clinically diagnosed prostate disease in LUTH within the study period. After en
      block removal, the prostate glands were fixed in formalin, weighed, sectioned at
      3-5mm intervals, processed and embedded in paraffin. Whole mount serial sections
      were stained with H& E and examined. RESULTS: Only 145 prostate glands were
      suitable for histological evaluation. There was an increasing prostatic weight
      with age. The distribution of identified prostatic lesions showed 75 (51.7%)
      having no histological diagnosis. Acute and chronic prostatitis accounted for 2
      (2.9%) each, benign prostatic hyperplasia alone, 52 (74.2%) while benign
      prostatic hyperplasia (BPH) associated with chronic prostatitis accounted for 7
      (10%). Latent prostate cancerwas found in 7 (10%) of the cases. CONCLUSION:
      Prostate weight increased with age. Acute prostatitis was found to be commoner in
      the younger age groups, particularly below 50 years while chronic prostatitis was
      seen more in the older men and was largely associated with BPH. BPH was found to
      be the commonest lesion. Latent carcinoma showed a prevalence of 10%, which is
      significant and in keeping with similar studies done elsewhere.

PMID- 24579502
TI  - A ten year review of diabetic retinopathy at the Guinness Eye Centre, Lagos
      University Teaching Hospital (LUTH), Idi-Araba, Lagos.
AB  - BACKGROUND: Diabetic retinopathy is an important complication of diabetes
      mellitus, which may lead to blindness. OBJECTIVE: The study is to analyze
      posterior segment lesions in Diabetes Mellitus patients seen in Guinness Eye
      Centre, Lagos University Teaching Hospital in relation to the number, duration
      and severity. METHODS: All the case files of Diabetes Mellitus patients seen
      during the period of study were retrieved and data extracted from them were
      analyzed. Such information included age, sex, duration of Diabetic Retinopathy
      and its severity. RESULTS: A total of 84 case files were reviewed. There were 47
      males and 37 females with a male to female ratio of 1.3:1. No diabetic patient
      was seen in the age group 30 years and below. Fifty-five (65%) patients who
      presented themselves did so very late. Of the 35 patients found to have diabetic
      retinopathy at presentation, 16 had the disease bilaterally. The most common form
      of Diabetic Retinopathy was clinically significant macula oedema. The study shows
      that a high proportion of the patients (41.6%) had Diabetic Retinopathy.
      CONCLUSIONS: Patients with DM should be referred early for eye examinations.
      Physicians Residents should be made to rotate through eye Departments for a
      period of at least 2 weeks so they can learn fundoscopy. Diabetic patients should
      be educated on the eye complications that may arise from their condition. Regular
      eye screening with fundus camera and laser therapy should be part of the routine
      management of Diabetics in Nigeria as is done in advanced countries.

PMID- 24579503
TI  - Citalopram and fluoxetine affects blood chemistry, hematology and brain serotonin
      in rats.
AB  - BACKGROUND: Depression is caused as a result of combination of genetic,
      biochemical, environmental, and psychological factors. Citalopram and fluoxetine
      are antidepressants which are considered the current standard for depression
      treatment. There are little or no reports as to whether these antidepressants
      affect blood chemistry and haematological parameters in humans. OBJECTIVE: The
      effects of citalopram and fluoxetine on blood chemistry, hematology and brain
      serotonin in rats were investigated. METHODS: Forty-five Sprague Dawley male
      albino rats (140.69 +/- 5.86g) were divided into 3 equal groups. The first group
      of rats were orally administered 2 ml of 0.25 mg/ml of citalopram, the second
      group was administered 2 ml of 0.25 mg/ml of fluoxetine and the third group was
      administered 2 ml of saline (0.89% NaCl) daily for 4 weeks. The body weights and
      feed intake of rats were recorded every other day throughout the duration of drug
      administration. Five rats from each group were sacrificed by cervical dislocation
      after 7, 14, 21 and 28 days of drug administration. Blood was taken intravenously
      into lithium heparinized tubes and brain excised. Blood chemistry and hematology
      were determined by auto analyzer, while brain serotonin levels were determined
      using High Performance Liquid Chromatography. Serum levels of creatinine, urea,
      albumin, protein, glucose and activities of aspartate aminotransferase (AST) and
      alanine amino transferase (ALT) were determined in rats administered citalopram,
      fluoxetine and saline. The packed cell volume, white blood cells, red blood cells
      and platelets of rats administered the respective drugs were determined. RESULTS:
      There was no significant (P > 0.01) difference in the mean body weight of rats
      administered fluoxetine, citalopram or saline for 2 weeks. There were no
      significant differences in the hematological parameters of rats. The results of
      the study showed that citalopram increase the body weight of rats in the third
      and fourth week and was reduced in fluoxetine administered rats. The drugs also
      affected brain serotonin level, lipid profile of rats and increased levels of
      albumin, glucose and activities of liver enzymes; aspartate aminotransferase and
      alanine aminotransferase. CONCLUSION: Data of the study indicate that oral
      administration of citalopram and fluoxetine in rats for 4 weeks daily affected
      blood chemistry and do not affect haematological parameters.

PMID- 24579505
TI  - Enhanced urinalysis in the detection of asymptomatic bacteriuria in pregnancy.
AB  - BACKGROUND: Detection and treatment of asymptomatic bacteriuria (ASB) in
      pregnancy is important to avert the attendant maternal and fetal morbidity. Other
      than urine culture, no other screening test is unequivocal. OBJECTIVE: The use of
      enhanced urinalysis test to detect ASB in pregnancy was investigated. METHODS:
      This was a prospective observational study which compared enhanced urinalysis
      with dipstick tests and urine culture. Clean catch midstream urine specimen was
      collected from 150 consecutive asymptomatic pregnant women. Tests of validity
      were used for comparison. RESULTS: Enhanced urinalysis detected bacteriuria as
      much as urine culture (4% vs. 4.7%). Itwas 57.1% sensitive and 98.6% specific. It
      had a false negative rate of 42.9% and was 96.7% accurate when compared to urine
      culture. Enhanced urinalysis took 1-2 hours to be done and required skills to use
      the microscope and was more expensive than dipstick urinalysis. CONCLUSION: The
      accuracy of enhanced urinalysis and its ability to detect ASB as much as urine
      culture connotes that it can be used to detect asymptomatic bacteriuria in
      pregnancy albeit only in secondary and tertiary health centres because of the
      cost and technicality involved.

PMID- 24579504
TI  - Perception of graduating medical students on child and maternal oral health in a
      selected tertiary institution in the southern part of Nigeria.
AB  - BACKGROUND: Oral health care imparts on the quality of life and general health
      outcomes, therefore essential for the knowledge of graduating medical students
      OBJECTIVE: To assess the knowledge of graduating medical students on child and
      maternal oral health METHODS: A cross sectional survey was undertaken among the
      graduating medical students of the University of Port Harcourt using an anonymous
      structured questionnaire with open and closed ended questions. Participants'
      knowledge about aetiology of dental caries, gingivitis and preventive oral health
      care and behaviours associated with early childhood caries (ECC) were assessed.
      Information gathered was collated and analyzed using a statistical software-SPSS
      Version 17. RESULTS: There were 166 participants with a mean age of 25.4 (+/-
      3.0) years, range 20-45 years. Over 80% knew the roles of diet and bacteria in
      aetiology of dental caries. Regarding ECC, 59% agreed that breast milk and infant
      formula may be harmful to the teeth and 41.4% were aware that a mother can
      transmit cariogenic bacteria to the child. The importance of dental check up in
      pregnancy and the association between oral diseases in pregnant women and infant
      health was known by 63.3% and 51.8% respectively. Also, the importance of age at
      first visit and frequency of routine dental visits in a child was known to 40.4%
      and 54.8% respectively. Only 12.7% of participants knew that a carious primary
      tooth should be restored. Over 90% agreed that they needed to increase their
      knowledge on child oral health. CONCLUSION: The knowledge base of graduating
      medical students on the subject of maternal and child oral health was inadequate.
      A curriculum review that accommodates clinical exposure to child and maternal
      oral health during undergraduate and postgraduate medical residency training in
      Paediatrics is advised to increase their knowledge.

PMID- 24579506
TI  - Hypercholesterolaemia in schoolchildren in Lagos, Nigeria: an indication of a
      growing threat of cardiovascular disease?
AB  - BACKGROUND: There is growing burden of cardiovascular disease in developing
      countries and the pathogenesis of artherosclerotic damage starts in childhood
      OBJECTIVE: The study is to examine the prevalence of hyperlipidaemia in
      schoolchildren in Lagos, as it relates to both socio-demographic and
      anthropometric correlates METHODS: A cross-sectional study was carried out among
      urban and rural adolescent schoolchildren aged between 10 and 19 years in Eti-Osa
      Local Government Area (EOLGA) of Lagos State. A structured questionnaire was used
      to get information relating to socio-demographic characteristics, family history
      of cardiovascular disease, lifestyle habits and socio-economic class, and the
      students were examined for height, weight and cholesterol levels. RESULTS: Two
      hundred and eighty eight subjects in the urban region and 72 subjects in the
      rural region of Eti-Osa LGA participated in the study. The mean age was 15.6 +/-
      2.2 years with a range of 10 to 18.9 years. The mean serum total cholesterol was
      148.1 mg/dl with a range of 100 to 254 mg/dl. There was significant correlation
      between serum cholesterol and gender only in the 12-13.9 year group. Neither
      place of residence nor age had any significant correlation to serum cholesterol.
      Thirteen (3.6%) students had elevated serum total cholesterol of e"200 mg/dl.
      Four subjects had BMls above the 95th centile, giving a prevalence rate of 1.1%.
      They were females, living and schooling in the urban area and three-quarters were
      of high socio-economic class. CONCLUSION: Strengthening pre-enrollment medical
      and physical examinations, regular measurement of weight, height and BMI and
      laying emphasis on important lifestyle modifications early in the formative years
      are important to prevent development of non-communicable disease later in life.

PMID- 24579507
TI  - Congenital lobar emphysema in a Nigerian neonate: a rare cause of neonatal
      respiratory distress.
AB  - Congenital lobar emphysema (CLE) is a notable cause of respiratory distress in
      neonates, however it remains a diagnostic challenge due to inadequate facilities
      and low level of experience. The management of this condition also is a bigger
      challenge due to paucity of expertise and relatively non-existent well-equiped
      neonatal intensive care unit in this part of the world. Here we present the case
      of a 5- day old baby who presented at Lagoon Hospital, Apapa with history of
      severe respiratory distress since birth. CT scan of the chest confirmed an
      emphysematous left upper lobe with contralateral mediastinal shift. The baby had
      a left posterolateral thoracotomy with left upper lobectomy and thereafter was
      electively ventillated for forty eight hours in the neonatal intensive unit. He
      had an uneventful postoperative course and was discharged from the hospital
      within one week forfollow-up in the clinic.

PMID- 24579508
TI  - Changes in blood glucose, lipid profile and antioxidant activities in trained and
      untrained adult male subjects during programmed exercise on the treadmill.
AB  - BACKGROUND: Exercise is a physical activity that maintains physical fitness and
      optimum health of an individual. OBJECTIVE: The objective of this study was to
      determine changes in redox-oxidative status, lipid profile, cortisol,
      testosterone and fasting blood glucose (FBG) in trained and untrained male
      subjects during a programmed exercise session. METHODS: Twenty (20) trained and
      twenty (20) untrained young healthy male subjects (age 21.75 +/- 1.15 years,
      height 1.74 +/- 0.02 m and weight 65.25 +/- 1.46 kg) participated in the study.
      Their weights, heights, waist and hip circumferences were measured. Subjects who
      have fasted for 12 hours exercised on the treadmill for 20 minutes at 1.5 km/hr
      after a warm-up period of exercising at 0.5 km/hr. for 3 minutes. Blood samples
      (1.5 ml) were withdrawn from the cubital vein before and immediately after the
      exercise session. Blood samples were analyzed for FBG, lipid profile,
      testosterone, cortisol and oxidative enzymes activities. Blood pressure and pulse
      rate were also measured before and after the exercise. RESULTS: There was a
      significant decrease in rate of glucose disappearance in the trained subjects
      compared with the untrained subjects. The low density lipoprotein (bad
      cholesterol), TC, TC:HDL and LDL:HDL ratios were significantly higher in the
      untrained subjects both before and after the exercise while the trained subjects
      recorded significantly low cholesterol level. Testosterone and cortisol were
      significantly higher in untrained subjects before the exercise while its level
      balanced up with that of the trained subjects after the exercise. There was a
      significant increase in pulse pressure and diastolic pressure in untrained
      subjects after the exercise compared with trained subjects. Results of
      antioxidant assay showed that basal GPx and catalase were significantly higher in
      the trained subjects while GSH and SOD significantly increased in untrained
      subjects after the programmed exercise. Trained subjects expressed efficient
      energy utilization with better preparedness to handle oxidative stress better
      than untrained subjects. CONCLUSION: Exercise improves body lipid profile,
      cardiovascular system and antioxidant status, thus providing better accommodative
      adjustment to changes without any significant change to blood pressure parameters
      during exposure to exercise training.

PMID- 24579509
TI  - Histolopathological patterns of cervical carcinoma seen at a radiotherapy centre
      in Ibadan, Nigeria.
AB  - BACKGROUND: The treatment of cervical carcinoma is dependent on many factors
      including histological types and degree of differentiation. Degree of
      differentiation is an important consideration in determining the prognostic
      outcome. OBJECTIVE: The study investigates the histological pattern and grades of
      cervical cancer tumours seen at a radiotherapy centre in Ibadan, Nigeria.
      PATIENTS AND METHOD: This retrospective study was carried out within Radiotherapy
      Department of University College Hospital, Ibadan. The records of patients
      diagnosed of cervical cancer seen between July 2008 and June 2010 were analysed.
      Data pulled out included age, disease stage at presentation, histological variant
      and degree of differentiation. RESULTS: 206 patients were seen during the period
      of which 196 had complete data. Squamous cell carcinoma (SCC) was seen in 178
      patients (i.e. 90.8%) while 14 patients (7.1%) had adenocarcinoma. One patient
      each had adenoid cystic carcinoma, adenosquamous carcinoma, clear cell carcinoma
      and mucinous carcinoma. Majority of the patients, 99 (50.5%) had poorly
      differentiated tumours, 64 (32.7%) had well differentiated tumours, while the
      rest 33 (16.8%) had moderately differentiated tumours. Of the SCC tumours, 95
      (53.4%) were poorly differentiated, 58 (32.6%) well differentiated while the
      remaining 25 (14%) were moderately differentiated. In comparison only 3 of the 14
      adenocarcinoma cases (21.4%) were poorly differentiated, 5 cases (35.7%) were
      well differentiated, while 6 (42.9%) were moderately differentiated. The
      difference in the degree of differentiation between squamous histology and
      adenocarcinoma was statistically significant (p value = 0.002). CONCLUSION:
      Poorly differentiated squamous cell carcinoma remains the leading variants of
      cervical cancer seen in our environment.

PMID- 24579510
TI  - Clinical investigation of patient related factors in non carious cervical
      lesions.
AB  - BACKGROUND: The majority of the studies on non carious cervical lesions (NCCLs)
      dealt with characteristics of NCCLs without identifying patient related factors
      associated with them. OBJECTIVE: The basis of this study to identify these
      factors and to see if there are any association with the findings. METHOD: This
      study was conducted among 34 patients referred to the conservative clinic of the
      Lagos University Teaching Hospital, Idi-araba, Lagos. Questions regarding
      patient's complaints, dietary habits and toothcleaning techniques were asked and
      correlated with the occurrence and severity of NCCLs clinically. RESULT: Over a
      third, (41.2%) of the subjects presented with dentine sensitivity resulting in
      pain. Fifty percent (50%) of the patients were on one form of medication or the
      other. Out of this number, 50% habitually chewed vitamin C tablets. With respect
      to diet, 61.8%, 58.8% and 47.1% of the patients were on diet rich in fruits, soft
      drinks and fruit juices respectively. The degree of severity(extensiveness) of
      lesions significantly increases with age of patient (p = 0.001). Tooth cleaning
      habits played an important role in the occurrence, distribution and pattern of
      NCCLs. There was association between the tooth cleaning technique used and the
      extensiveness and distribution of the lesions. The horizontal technique accounted
      for 54.7% of lower jaw lesions while 63.7% and 55.8% of lesions found in the
      vertical and mixed (circular) techniques respectively were found in the upperjaw.
      CONCLUSION: Awareness of the multifactorial etiology in noncarious cervical
      lesions may help the clinician to formulate an appropriate treatment plan and
      preventive strategies in the management of NCCLs.

PMID- 24579511
TI  - Regression equation for estimation of length of humerus from its mophometry in a
      Nigerian population.
AB  - BACKGROUND: While intact long bones are most ideal in estimation of the stature
      of unidentified individual, in forensic cases as may occur when natural or man
      made disasters present bone fragments, regression equations derived from
      measurements of these bone fragments have been used to determine the length of
      the intact long bone. OBJECTIVE: The study reports on the morphometry of the
      humerus and the estimation of its length using regression equations in a Nigerian
      population. METHODS: The maximum length of the humerus was measured using an
      osteometric board while theAnatomical neck circumference (ANC), Anatomical neck
      diameter (AND), mid shaft diameter (MSD), olecranon vertical diameter (OVD),
      olecranon transverse diameter (OTD), transverse diameter of the inferior
      articular surface (IASD), transverse trochlea diameter (TTD) proximal point of
      the caput humeri and collum anatomicum (CHCAD), proximal edge of the fossa
      olecrani (PEFO) and the most distal point of trochlea humeri (FOTHD) and the
      biepicondylar width (BEW) of the distal segment were measured using a digital
      vernier caliper. Partial correlation and Persian regression were used to derive
      the linear regression equations for the measured parameters that showed
      correlation with the humeral length. RESULTS: Estimation of the maximum length of
      the humerus from the measures of its ANC, FOTHD, and MSD was achieved with
      relative accuracy. In deriving regression equations for the length of the humerus
      of the right and left sides, irrespective of side, the ANC and MSD were both
      significant in estimating the maximum length of the humerus; on the right side
      only the ANC exhibited significant correlation, while on the left side both the
      ANC and FOTHD exhibited significant correlation. CONCLUSION: These previously
      unreported findings may help in anthropometric, forensic, and archaeological
      investigations for the estimation of the stature of the remains of unknown bodies
      by using regression equations in a Nigerian population.

PMID- 24579512
TI  - The use of ultrasound guided transvaginal probe on the anterior abdominal wall
      for follicular aspiration in a patient with inaccessible ovaries by transvaginal
      ultrasound.
AB  - OBJECTIVE: To evaluate the effectiveness of ultrasound guided tranvaginal probe
      placed on the anterior abdominal wall for oocyte retrieval in a patient whose
      ovaries were not visible trans-vaginally. DESIGN: A case report SETTING: Medical
      ART Center, Nigeria- Private IVF clinic with an academic setting PATIENT(S): A 35
      yr old woman undergoing IVF treatment with ovaries difficult to visualize trans
      vaginally having ovarian stimulation pressure effect. INTERVENTION(S): Ultrasound
      guided oocyte aspiration through the abdominal wall using the trans-vaginal
      probe. MAIN OUTCOME MEASURES: Number of oocytes retrieved. RESULTS: 9 oocytes
      were successfully aspirated using the ultrasound scan guided probe placed over
      the anterior abdominal wall. CONCLUSION: Successful oocyte retrieval can be
      achieved via the abdominal puncture with the aid of a trans-vaginal ultrasound
      probe placed on the abdominal wall.

PMID- 24579513
TI  - Eventration of the diaphragm--case reports and review of the literature.
AB  - Eventration of the diaphragm can have varied symptomatology. We present three
      cases that presented with features suggestive of gastric outlet obstruction,
      productive cough of acute onset, and traumatic diaphragmatic rupture
      respectively. They were successfully treated with plication of affected
      hemidiaphragm. We also reviewed existing literature on the subject with
      presentation of our findings.

PMID- 24579514
TI  - Chronic ulcers in Ikeja-Lagos, Nigeria: an eighteen month review of infecting
      bacterial agents and susceptibility pattern.
AB  - BACKGROUND: Chronic ulcers are an important cause of morbidity among surgical and
      medical patients. Infection in ulcers may delay healing and cause septicemia
      resulting in mortality. Microbial studies are important for the appropriate
      management of these ulcers. OBJECTIVE: The study investigates on eighteen month
      review of infecting bacterial agents and susceptibility pattern in chronic ulcers
      in Lagos, Nigeria. METHODS: Details of all patients treated for ulcers that were
      investigated at the department of Medical Microbiology and Parasitology, Lagos
      State University Teaching Hospital, Ikeja-Lagos, Nigeria between July 1st 2009
      and December 31, 2010 were retrieved from the computer database and transferred
      into the proforma designed for the study. Data collected were demography, date of
      onset of ulcer, mode of specimen collection, names of isolates and drug
      sensitivity patterns. RESULTS: A total of 329 cases were seen and reviewed during
      the study period. Males constituted 50.2%, females 38.3% and the gender of the
      remaining 11.6% were not indicated. There were 259 (78.7%) adults and 42 (12.8%)
      children. The ages of 28 cases were not indicated. Microbial growths were
      obtained in 217 (66.7%) patients. Gram negative (Gn) organisms were isolated in
      181(83.5%) and Gram positive (Gp) in 35 (16%). The most common isolates were
      Pseudomonas aeruginosa (19.1%) Staphylococcus aureus (9.7%), Proteus mirabilis
      (7.6%) and Escherichia coil (7.3%). There were widespread resistances by the
      isolates to the common antibiotics in the study environment. CONCLUSION: The wide
      spread resistance may be due to lack of an antibiotic use policy. Certain
      antibiotics should be reserved for second line treatment in the emergency setting

PMID- 24579515
TI  - Evaluation of the effects of the metals Cd, Cr, Pb and their mixture on the
      filtration and oxygen consumption rates in catarina scallop, Argopecten
      ventricosus juveniles.
AB  - In this work, we evaluated the effect of sublethal concentrations ( LC25, LC10
      and LC5) of cadmium, chromium, lead, and their mixture on the filtration rate and
      oxygen consumption rate of Catarina scallop, Argopecten ventricosus (Sowerby,
      1842), juveniles, in order to evaluate the use of these biomarkers as a reliable
      tool in environmental monitoring studies, because these metals have been found at
      high levels in water and sediments in the Mexican Pacific systems. An inverse
      dose-response relationship was observed when metal concentration and exposure
      time increased, the filtration rate and oxygen consumption rate reduced. The
      physiological responses evaluated in this study were sufficiently sensitive to
      detect alterations in the organisms at 0.014 mg l(-1) Cd, 0.311 mg l(-1) Cr,
      0.125 mg l(-1) Pb and 0.05 mg l(-1) Cd + Cr + Pb at 24 and 72 hrs. Cd showed the
      most drastic effect. The Catarina scallop juveniles were more sensitive to Cd, Cr
      and Pb as compared to other bivalves. The biomarkers evaluated are a reliable
      tool to carry out environmental monitoring studies.

PMID- 24579516
TI  - Are the shells of Scrobicularia plana useful for monitoring trace metal pollution
      events?
AB  - The rupture of a mine dam in Aznalcollar (SW Spain) in April 1998 entailed the
      contamination of Guadalquivir River and its estuary. To study the ability of
      bivalve shells to monitor the temporal changes on metal composition in the area,
      two year old Scrobicularia plana were obtained from two different locations of
      the estuary (Pantalan highly influenced and Pantoca less influenced) during the
      year 2000 and 2007. Co, Hg, Mo, Ni and Zn content was measured in shell and soft
      tissue of S. plana. Metal composition in shells sampled by micromilling and
      corresponding to the years 1999, 2000, 2006 and 2007 was higher in Pantalan (Co:
      5.88 +/- 2.7 microg g(-1); Hg: 0.04 +/- 0.03 microg g(-1); Mo: 0.41 +/- 7.90
      microg g(-1); Ni: 37.66 +/- 25.56 microg g(-1) and Zn: 9.19 +/- 8.88 microg g(
      1)) than in Pantoca (Co: 3.64 +/- 0.50 microg g(-1); Hg: 0.02 +/- 0.02 microg g(
      1); Mo: 4.70 +/- 1.20 microg g(-1); Ni: 7.21 +/- 13.60 microg g(-1) and Zn: 3.90
      +/- 1.89 microg g(-1)). A marked temporal decrease was observed for all metals in
      Pantalan station with concentrations of Co, Hg, Mo, Ni and Zn varying
      respectively from 7.35 +/- 3.02, 0.05 +/- 0.03, 19.90 +/- 2.40, 70.58 +/- 21.94
      and 18.04 +/- 0.98 microg g(-1), in 1999 to 3.07 +/- 1.08, 0.009 +/- 0.001, 2.40
      +/- 1.43, 10.11 +/- 3.80 and 1.11 +/- 0.33 microg g(-1) in 2007, indicating that
      the effect of the mine accident had diminished significantly. Metal content in
      soft tissues did not follow the same decreasing trend indicating that soft
      tissues present a different capacity to accumulate metals from the environment.
      Our results confirm that micromilling shells are a suitable tool to assess
      bioaccumulation ofcontaminants during the entire life-span of bivalves.

PMID- 24579517
TI  - Pesticide residue analyses and biomarker responses of native Costa Rican fish of
      the Poeciliidae and Cichlidae families to assess environmental impacts of
      pesticides in Palo Verde National Park.
AB  - Pesticide chemical residues in water samples and biomarker responses in
      transplanted fish were used to monitor environmental hazards of pesticides in
      Palo Verde National Park (Costa Rica). The Costarican fish, Parachromis dovii
      (Ciclhidae) and Poecilia gillii (Poecillidae), were selected as sentinel species.
      Contaminant analyses detected up to 15 different pesticide residues in water with
      hexachlobenzene (2261 ng l(-1)), phorate (473 ng l(-1)), epoxiconazole (314) and
      bromacil (117 ng l(-1)) being the compounds found in higher concentrations.
      Biomarker responses evidenced impacts on cholinesterase activities in
      transplanted fish at Barbudal site probably due to the presence of
      organophosphate insecticides such as phorate. High enzyme activities of
      glutathione S-transferase and catalase and elevated levels of lipid peroxides
      were also observed at a site impacted by rice fields (Cabuyo); those effects
      could be associated with the presence of hexachloro benzene and triazole
      fungicides. In general, P. dovii biomarkers were affected to a greater extent
      than those of P. gillii in fish transplanted to sites associated with
      agriculture, which suggests the former species is a good candidate for future
      surveys.

PMID- 24579518
TI  - Pesticide exposure on sloths (Bradypus variegatus and Choloepus hoffmanni) in an
      agricultural landscape of Northeastern Costa Rica.
AB  - Between 2005 and 2008, wild Bradypus variegatus and Choloepus hoffmanni
      inhabiting an agricultural landscape and captive animals from a rescue center in
      Northeastern Costa Rica were studied to assess exposure to pesticides. A total of
      54 animals were sampled: 42 wild sloths captured at an agricultural landscape and
      12 captive animals from a rescue center. Pesticides' active ingredients were
      determined in three sample matrices: hair, aqueous mixture (paws' wash) and
      cotton gauze (mouth clean) based on multi-residue gas chromatography methods.
      Recoveries tests ranged from 73 to 146% and relative standard deviations were
      less than 20% throughout all the recovery tests. Active ingredients detected in
      sloths samples were ametryn, chlorothalonil, chlorpyrifos, diazinon,
      difenoconazole, ethoprophos and thiabendazole. These active ingredients were used
      in intensive agricultural production for bananas, pineapples and other crops.
      Blood plasma cholinesterase activity (PChE) was determined by the Ellman method
      modified for micro plates. Enzyme activity determination was normalized to
      protein content in the samples according to Bradford method. Wild sloth PChE
      activity was similar for both species while sloths in captivity showed
      differences between species. Enzyme activity was significantly lower for two-toed
      sloths. This study showed that sloths were exposed to pesticides that caused
      acute and chronic effect in mammals and can also be a threat to other wildlife
      species. There is a need to better understand the potential effects of exposure
      to pesticides in sloths and other wild mammal populations, especially those
      threatened or endangered. More studies in this field must be carried out on the
      wildlife fauna inhabiting the agricultural landscape and its surroundings.

PMID- 24579519
TI  - Use of cholinesterase activity as a biomarker of pesticide exposure used on Costa
      Rican banana plantations in the native tropical fish Astyanax aeneus (Gunther,
      1860).
AB  - In Costa Rica, thousands of tones of agricultural pesticides have been used for
      decades and their use is continuously increasing due to intensive and expanding
      production of coffee, pineapple, rice, ornamental plants and bananas. The
      objective of this study was to evaluate whether choline esterase (ChE) activity
      could be used as a biomarker of exposure to pesticides in the Costa Rican native
      fish Astyanax aeneus (characidae). Three methods used in order to evaluate the
      ChE biomarker were as follows: Laboratory studies where A. aeneus was exposed to
      organophosphate pesticide (ethoprophos); In situ 48 hr exposure assessment using
      caging experiments with fish exposed upstream and downstream of banana
      plantations and ChE activity estimation of in fish captured directly at sites
      with different degrees of pesticide exposure. Results from the laboratory studies
      showed that ChE activity in both brain and muscle tissue was significantly lower
      in fish exposed to ethoprophos than in controls. Fish from the caging experiments
      showed no difference in ChE activity neither in brain nor in muscle tissue
      between the four tested sites and was attributed to the short duration of the
      exposure. Asignificant difference in ChE activity was determined in muscle of
      fish captured from Laguna Madre de Dios compared to fish from Canal Batan.
      Although our laboratory results revealed that ChE activity in A. aeneus was
      highly responsive to ethoprophos, results from field experiments were less
      conclusive and showed that the captured fish showed large variability in ChE
      activity and that more research is needed before ChE activity can be used as
      reliable biomarker of pesticide exposure.

PMID- 24579520
TI  - Environmental hazards associated with pesticide import into Costa Rica, 1977
      2009.
AB  - Raw pesticide import data from 1977 to 2009 obtained from the Ministry of
      Agriculture in Costa Rica were processed and analyzed. The quantity of specific
      active ingredients (a.i.), and chemical groups were calculated by year and
      presented in ten-year periods. Three sets of environmental hazard indicators were
      constructed: one for general pesticides exposure to monitor tendencies in time,
      including total quantities imported divided by significant denominators, such as
      hectares of protected and wetland areas. The second indicator calculates
      pesticide use on the Pacific or Caribbean slope. The third one is an assessment
      of environmental hazards intended to estimate fate and toxicity to aquatic biota.
      A review of Costa Rican aquatic ecosystems' contamination with pesticides is
      presented. The annual average import as well as the quantity of pesticides
      capable of reaching water bodies increased during the analyzed period. The same
      was observed for harmful a.i., 98% of the pesticides imported were classified as
      acutely toxic for fish and crustaceans and 73% for amphibians. Approximately 8.4
      kg of a.i. were imported per hectare of protected areas and 24.3 kg of a.i. per
      hectare of wetlands. The contamination of aquatic systems over time by specific
      pesticides matches quite well the list of imported ones. We recommend using data
      of pesticide imports as a source of information to evaluate environmental risk
      exposure and promote changes to reduce impacts on aquatic systems.

PMID- 24579521
TI  - Effect of malathion on the demography of Daphnia pulex Leydig and Diaphanosoma
      birgei Korinek (Cladocera).
AB  - Malathion is a common pesticide used to control insects in agricultural, domestic
      and industrial sectors in different parts of the world. In this work we evaluated
      the effects of sublethal concentrations of malathion on the survivorship and
      reproductive variables of two cladoceran species Daphnia pulex and Diaphanosoma
      birgei using standard life table demography method. Based on preliminary tests,
      we selected four sublethal concentrations of malathion for each cladoceran
      species. For D. pulex, the malathion concentrations were 0. 225, 0.45, 0.9 and
      1.8ng I(-1) and for D. birgei, these were 0.0281, 0.0562, 0.1125, 0.225ng I(-1).
      Our results showed that in general, Daphnia pulex was less sensitive than
      Diaphanosoma birgei to malathion. The average lifespan of Daphnia pulex in
      controls was about 19 days while under similar conditions, that of D. birgei was
      about 21 days. For either cladoceran species, increased pesticide concentration
      resulted in decreased survival; this was more evident in the treatment containing
      the highest concentration of malathion (0.225 ng l(-1)) for D. birgei. Fecundity
      of D. pulex and D. birgei also decreased with increase in the concentration of
      malathion. For a given cladoceran species, compared to controls, the gross
      reproductive, net reproductive rates and the population growth rate significantly
      decreased due to malathion. Compared to the survivorship variables (age-specific
      survival, life expectancy and average lifespan), the reproductive parameters
      (gross reproductive rate, net reproductive rate and the rate of population
      increase) of the two cladoceran species were decreased by the pesticide.

PMID- 24579522
TI  - Sensitivity of Costa Rica's native cladoceran Daphnia ambigua and Simocephalus
      serrulatus to the organophosphate pesticide ethoprophos.
AB  - The study of pesticide toxicity in aquatic environments is assessed with
      ecotoxicological tests and most research has been performed using species from
      temperate regions. In the present study, series of acute (48 hrs) toxicity tests
      to compare the sensibility of two indigenous cladocera of Costa Rica and two
      reference species were used in temperate regions to the organophosphate
      pesticide, Ethoprophos. Additionally, reproduction tests using S. serrulatus with
      sub lethal concentrations of ethoprophos and a control were assayed to check its
      sensitivity over a longer period exposure. The sensitivity of Costa Rica's native
      species Daphnia ambigua (EC50 48 hr: 12.9 +/- 3.0 microg(l(-1)) and Simocephalus
      serrulatus (10.6 +/- 2.1 microg l(-1)) to ethoprophos were higher (p < 0.05) when
      compared to the exotic species Daphnia magna (289.8 +/- 77.4 microg l(-1)), and
      were comparable to that of the more widely distributed species, Ceriodaphnia
      dubia (18.2 +/- 5.2 microg l(-1)). No effect on S. serrulatus reproduction was
      observed at concentrations between 1 and 4 microg l(-1). This study provides
      information that can be considered in the selection of species for ecosystem
      studies of pesticide toxicity in neotropical regions.

PMID- 24579523
TI  - Effect of pesticides used in banana and pineapple plantations on aquatic
      ecosystems in Costa Rica.
AB  - Current knowledge on fate and effect of agricultural pesticides comes is mainly
      from temperate ecosystems. More studies are needed in tropical systems in order
      to assess contamination risks to nontarget endemic tropical species from the
      extensive use of pesticides e.g. in banana and pineapple plantations. In this
      study, acute laboratory toxicity tests with organophosphate pesticides
      ethoprophos and chlorpyrifos were conducted on two Costa Rican species,
      cladoceran Daphnia ambigua and fish Parachromis dovii. Tests showed that
      chlorpyrifos was more toxic than ethoprophos to D. ambigua and P. dovii and that
      D. ambigua was also more sensitive than P. dovii to both pesticides.
      Additionally, bioassays were performed by exposing D. magna and P. dovii to
      contaminated water collected from the field. Chemical analyses of field water
      revealed that fungicides were generally the most frequent pesticide group found,
      followed by insecticides/nematicides and herbicides. The bioassays and values
      obtained from the literature confirmed that D. magna was more sensitive to
      pesticide contamination than P. dovii and that D. ambigua was more sensitive than
      D. magna, suggesting that the native cladoceran is a more suitable test species
      than its temperate counterpart. Species sensitivity distributions showed no
      significant difference in sensitivity between tropical and temperate fish and the
      arthropod species exposed to chlorpyrifos in this study. Choline esterase
      activity (ChE) was measured in P. dovii in laboratory tests in order to assess
      the applicability of this biomarker. ChE inhibition in P. dovii was observed in
      the laboratory at levels below the LC10 of both ethoprophos and chlorpyrifos,
      confirming that ChE is an efficient biomarker of exposure. Both indigenous Costa
      Rican species used in this study were found to be suitable standard tropical test
      species. Further studies are needed to investigate how protective the safe
      environmental concentrations, derived from LC50 of native tropical species, are
      for protecting tropical aquatic natural communities.

PMID- 24579524
TI  - Hazard prioritization and risk characterization of antibiotics in an irrigated
      Costa Rican region used for intensive crop, livestock and aquaculture farming.
AB  - Antibiotics alter the homeostasis of microbial communities and select for
      antibiotic-resistant bacteria in the wild. Thus, the accumulation of unnaturally
      high concentration of these substances in the environment due to their use in
      human activities can be regarded as a neglected form of pollution, especially in
      countries with agricultural-based economies. Qualitative and quantitative
      information on antibiotic usage in Costa Rica is scarce, hence the design and
      enforcement of prevention strategies and corrective measures is difficult. To
      address this issue, and aiming in the long run to contribute with a more rational
      use of pharmaceuticals in the tropics, we characterized the hazard associated
      with the antibiotics used during 2008 in agriculture, aquaculture, pig farming,
      veterinary medicine and human medicine in the major irrigation district of Costa
      Rica. Hazard indicators were calculated based on antibiotic use and a weighted
      algorithm that also considered antibiotic fate, toxicity, and resistance.
      Moreover, hazard quotients were computed using maximum environmental
      concentrations reported for Costa Rican surface waters and predicted no effect
      concentrations for aquatic organisms. The number of antibiotics used in the ATID
      during the study were n = 38 from 15 families. Antibiotic consumption was
      estimated at 1169-109908 g ha(-1) year(-1) and, distinctively, almost half of
      this figure was traced back to phenicols. Tetracyclines, with a particular
      contribution of oxytetracycline, were the most widely used antibiotics in
      agriculture and veterinary medicine. Oxytetracycline, florfenicol,
      chlortetracycline, sulfamethoxazole, erythromycin, ciprofloxacin, enrofloxacin,
      sulfamethazine, trimethoprim and tylosin, in that order showed the highest hazard
      indicators. Moreover, hazard quotients greater than 1 were calculated for
      oxacillin, doxycycline, oxytetracycline, sulfamethazine, and ciprofloxacin.
      Studies dealing with the ecotoxicology of tetracyclines, sulfonamides and
      quinolones, as well as surveys of phenicol resistance among environmental
      bacteria, should be prioritized in Costa Rica.

PMID- 24579525
TI  - Development of quantitative RNA biomarkers for detecting dioxin-like and
      estrogenic pollutants in Costa Rican native fish species.
AB  - Monitoring the environmental impact on native species is crucial for the correct
      management of tropical ecosystems. The Costa Rican fish Parachromis dovii
      (Cichlidae) and Poecilia gillii (Poecillidae) were used as sentinel species for
      freshwater bodies under considerable pressure by intensive agriculture Cichlidae
      development. Suitable qRT-PCR probes for the quantification of hepatic mRNA
      levels of two stress-related genes--vitellogen in (estrogenic effects) and
      cytochrome P4501A(CYP1A, dioxin-like compounds)--for both species were designed
      and validated in experimental treatments with model effectors (17beta-estradiol
      and beta-naphtoflavone, respectively), demonstrating their usefulness as markers
      of exposure to these two kinds of pollutants. Analysis of fish transplanted
      across pesticide contaminated sites near Palo Verde National Park, Pacific Coast
      of Costa Rica did show significant changes on hepatic Cyp1A in both species. In
      P. dovii, Cyp1A levels were enhanced in Barbubal and in the impacted Cabuyo sites
      in the rainy season whereas in P. gillii fish Cyp1A transcripts were down
      regulated differently across rainy and dry seasons. Vitellogen in mRNA levels in
      P. gillii varied between males and females with males showing always low values
      which indicated no estrogenic effects. Within females, vitellogenin levels varied
      over 100,000 fold depending on their maturation stage, further demonstrating the
      ability of the method to monitor changes (natural or induced) in the reproductive
      system of the fish.

PMID- 24579526
TI  - Ecotoxicological evaluation of aquaculture and agriculture sediments with
      biochemical biomarkers and bioassays: antimicrobial potential exposure.
AB  - Inappropriate practices and lack of regulations regarding antimicrobial use in
      agricultural production of developing countries increase the risk of exposure to
      aquatic ecosystems. Sediments may act as sink of antimicrobial compounds and can
      provide a historical record of pollution. In the present study, toxic potential
      of sediments receiving effluents from a fish farm (TIL1), rice farm (AZ) and
      swine farm (RD2) and from a reference natural wetland (PV) in a tropical dry
      region was evaluated. According to local surveys of antimicrobials and national
      product registries, sites were classified from highest to lowest potential
      exposure as following: RD2>TIL1>AZ>PV. Both, whole sediment and interstitial
      water tests, showed a high toxicity of pig farm sediments to the behavior of
      Anodontites luteola and the survival of Daphnia magna (EC50 -48hrs: 2.4 -11.8%)
      (ANOVA, p < 0.05). Integrated responses from Cholinesterase activity (ChE),
      Gluthathion-S-transferase (GST) and Lipoperoxidation (LPO) measured in A. luteola
      tissue pointed at the pig and rice farms as sites influenced by activities with
      an intensive use of xenobiotic substances. The assessment of toxicity pointed at
      the need of more research on sub-lethal effects of antimicrobials on aquatic
      invertebrates. With this purpose, we analyzed biomarker response of A. luteola to
      oxytetracycline in vitro and found a decrease of ChE and GST in concentrations of
      100 microg I(-1).

PMID- 24579527
TI  - Effect of paracetamol and diclofenac on population growth of Plationus patulus
      and Moina macrocopa.
AB  - Two non-steroidal anti-inflammatory commonly used in Mexico are paracetamol and
      diclofenac. These drugs reach natural waterbodies transport through the
      hydrological areas of agriculture and effluent treatment plants and can affect
      plankton. In this study, we quantified the chronic effects of paracetamol and
      sodium diclofenac on the population dynamics of the rotifer Plationus patulus and
      the cladoceran Moina macrocopa under laboratory conditions. Both these species of
      zooplankton are common in freshwaters and are sensitive to chemicals in the
      medium. Our results showed that densities of both P. patulus and M. macrocopa
      decreased with increasing levels of both the analgesic drugs. Both zooplankton
      species did not survive beyond when paracetamol was applied at 32 mg I(-1) in the
      medium. Diclofenac in general had more adverse effect than paracetamol for either
      zooplankton species. P. patulus was more sensitive than M. macrocopa to both
      analgesic drugs. When diclofenac was present in the medium at > or = 12.5 mg I(
      1), rotifer reproduction was inhibited, while the tested cladocerans continued to
      grow but to lower densities compared to control. The rate of population increase
      (r) per day of P. patulus and M. macrocopa was significantly and inversely
      related to the concentration of paracetamol and diclofenac in the medium.
      However, the relationship between r and drug concentration differed depending on
      the zooplankton species and drug. In controls, the r of P. patulus was 0.18 d(
      1), for M. macrocopa under similar conditions, it was slightly lower (0.16 d(
      1)). The rvalues of both zooplankton populations became negative (-0.10 to -0.15
      d(-1)) when exposed to paracetamol at 32 mg l(-1) or diclofenac at 25 mg I(-1).

PMID- 24579528
TI  - Tolerance of Myriophyllum aquaticum to exposure of industrial wastewater
      pretreatment with electrocoagulation and their efficiency in the removal of
      pollutants.
AB  - The wastewater used in this study was obtained from a treatment plant where it
      mixed with wastewater of 142 industries and was treated using electrocoagulation
      with iron electrode and phytoremediation with Myriophyllum aquaticum, likewise
      certain biomarkers of oxidative stress of the plant were evaluated to find out
      its resistance to contaminant exposure. Electrocoagulation was performed under
      optimum operating conditions at pH 8 and with a current density of 45.45 A m(-2)
      to reduce the COD by 42%, color 89% and turbidity 95%; the electrochemical method
      produces partial elimination of contaminants, though this was improved using
      phytoremediation. Thus the coupled treatment reduced the COD by 94%, color 97%
      and turbidity 98%. The exposure of M. aquaticum to electrocoagulated wastewater
      did not have an effect on the ratio of chlorophyll a/b (2.84 + 0.24); on the
      activity of SOD, CAT and lipoperoxidation. The results show the potential of M.
      aquaticum to remove contaminants from pretreated wastewater since the enzymatic
      system of the plants was not significantly affected.

PMID- 24579530
TI  - Petroleum hydrocarbons, fluorescent aromatic compounds in fish bile and
      organochlorine pesticides from areas surrounding the spill of the Kab121 well, in
      the Southern Gulf of Mexico: a case study.
AB  - In October 2007, a light crude oil spill took place in the off shore Kab121 oil
      well, 32 km north of the mouth of the Grijalva River, Tabasco, Mexico. In order
      to estimate the possible effects of oil spill on the biota in the area
      surrounding the spilled well, the level of different fractions of petroleum
      hydrocarbons were measured in fish, as well as the concentration of some
      chlorinated hydrocarbons and PCBs. The organisms examined were cat fish (Ariopsis
      felis), in addition fluorescent aromatic compounds in bile, the contaminants
      above mentioned and their relationship with cyotochrome P-450 and Ethoxyresorufin
      O-deethylase, Glutathion-S-Transferase and catalase activities in liver were
      determined. The concentration of most pollutants were low, except PAHs. Spatial
      distribution of these compounds, as well as most biomarkers, reflected the
      highest exposure of fish to pollutants in the area adjacent to well, as well as
      in the proximity of rivers. The profile of exposure to this environment was
      chronic in nature and not temporary.

PMID- 24579529
TI  - Assessing the health condition profile in the freshwater fish Astyanax aeneus in
      Champoton River, Mexico.
AB  - The use of biomarkers for monitoring aquatic environmental quality has gained
      considerable interest worldwide. The effects of the environmental conditions of
      Rio Champoton, Mexico, in the hotspot of Mesoamerica, were assessed in Astyanax
      aeneus, a native fish of the tropics of southwestern Mexico. Pollution from
      agrochemical residues is a major problem in Rio Champoton. Three study sites
      along the freshwater portion of the river were monitored in April, July, and
      November 2007 and February 2008. This study includes a water quality index, a set
      of biomarkers (hepatic glycogen levels and lipid peroxidation in liver, gills,
      and muscle) to assess the integrated biomarker response, and population
      bioindicators (gonadosomatic and hepatosomatic indices and Fulton's condition
      factor). Although the water quality index suggested low level of contamination in
      the Rio Champoton, biomarkers indicated that A. aeneus is exposed to stressors
      that impair biological responses. The integrated biomarker response showed stress
      periods with higher biomarker response and recovery periods with decreasing
      biomarker values. The somatic indices did not indicate severe effects at the
      population level. This study illustrates the usefulness of lipid peroxidation
      evaluation in the assessment of aquatic health conditions and corroborates the
      suitability of A. aeneus as a sentinel species.

PMID- 24579531
TI  - A prospective study of wound infections after laparotomy in obstetrics and
      gynaecology department.
AB  - Postoperative wound infection is of great importance to both surgeon and patient.
      All surgeons know that postoperative wound infection means morbidity, anxiety,
      longer hospitalization, higher cost; not to forget the embarrassment to the
      surgeons. However, it is still a common surgical complication despite other
      advances in modern medicine. This study was conducted to find out the incidence
      of postoperative wound infection and to survey the risk factors for wound
      infection in obstetrics and gynaecology department of Nepal medical college
      teaching hospital (NMCTH). A prospective study of all the cases with infected
      wound after laparotomy and lower segment cesarean section done in NMCTH in
      obstetrics and gynaecology department was carried out in this study from Chaitra
      2068 to Falgun 2069. The frequency of wound infection was 5.87%. Most of the
      wound infection after lower segment cesarean section occurred in emergency cases
      (16 out of 19). Seventy percent of patients had preoperative hospital stay range
      of 0-2 days whereas the range was 3-18 days for the rest 30%. The range of blood
      loss was 150-300 ml in nearly 75.7 % of patients. Duration of operation was 1-2
      hours in 89.2% cases. Only 48.6% of wound infection was identified within 8th
      postoperative day. Number of infected cases getting prophylactic antibiotic was
      25 (67.6%). BMI was >25 in 62.2% of patients. Type of skin incision was
      pfannenstiel in 94.6%. Skin was closed subcuticularly with vicryl no. 1 in 81.1%.
      Staphylococcus aureus was isolated in swab culture in 24.3%. Resuturing was
      required in 18.9% of cases.

PMID- 24579532
TI  - Role of USG guided FNAC in diagnosis of abdominal and thoracic lesions.
AB  - A prospective study was carried out during 2010 - 2012 in which a total of 194
      patients underwent USG guided FNAC from lesions in deep seated thoracic and
      abdominal organs. These included liver, lungs, intra-abdominal lymphnodes, gall
      bladder, ovary and adnexa, pancreas, stomach, omentum, other mass of unknown
      origin in peritoneal cavity, mediastinum, kidney, colon, small intestine, pleura,
      appendix and adrenal gland. Of these, FNAC was diagnostic in 168 (86.7%) cases,
      in 15 (7.7%) cases it was not conclusive. In next 6 (3.1%) it was suspicious of
      malignancy and the smears were acellular and /or contained blood only in 5 (2.6%)
      cases. Of all diagnosed cases, 153 (78.9%) cases were malignant, 28 (14.4%) were
      non-noplastic which included inflammatory, infective and granulomatous lesions
      and 13 (6.7 %) were benign neoplastic lesions. In liver, metastatic
      adenocarcinoma was the most common FNAC diagnosis, in lungs non-small cell
      carcinoma. The aim of this study was to evaluate the overall role of USG guided
      FNAC in diagnosis of abdominal and thoracic lesions.

PMID- 24579533
TI  - Adenosine deaminase in CSF and pleural fluid for diagnosis of tubercular
      meningitis and pulmonary tuberculosis.
AB  - Tuberculosis (TB) is one of the most common infectious diseases in developing
      countries including Nepal. Delay in diagnosis and treatment of tuberculosis
      results in poor prognosis of the disease. This study was conducted to estimate
      diagnostic cut off values of Adenosine Deaminase (ADA) in cerebrospinal fluid
      (CSF) and pleural fluid and to evaluate the sensitivity, specificity, positive
      and negative predictive values ofADA in pleural fluid and CSF from patients with
      tuberculous and non-tuberculous disease. A total of 98 body fluid (CSF: 24,
      Pleural fluid: 74) specimens were received for the estimation of ADA. ADA
      activity was measured at 37 degrees C by spectrophotometric method of Guisti and
      Galanti, 1984 at 625nm wavelength. Among the patients enrolled for the study
      subjects for which CSF were received (n = 24) included 8 tuberculous meningitis
      (TBM), and 16 non-tubercular meningitis (NTM). Pleural fluid samples (n = 74)
      were received from 19 pulmonary TB with pleural effusion, 17 PTB without pleural
      effusion and 37 of non-tuberculous disease patients. CSF ADA activity were (11. 1
      +/- 2.03 IU/L) and (5.3 +/- +1.89 IU/L) (p <00001) in TM and non-NTM groups and
      Pleural fluid ADA activity were (10 +/- 22.18 IU/L) and (23.79 +/- 11.62 IU/L) (p
      < 0.001) in PTB and non-TB groups respectively. ADA test in body fluids, which is
      simple, cost-effective and sensitive, specific for the tubercular disease is
      recommended to perform before forwarding the cumbersome and expensive procedures
      like culture and PCR for TB diagnosis.

PMID- 24579534
TI  - Pattern of dyslipidemia and evaluation of non-HDL cholesterol as a marker of risk
      factor for cardiovascular disease in type 2 diabetes mellitus.
AB  - People with type 2 Diabetes have an elevated risk for developing cardiovascular
      disease (CVD) for which dyslipidemia is the major contributor. Diabetic patients
      have characteristic pattern of dyslipidemia with decreased level of high density
      lipoprotein cholesterol (HDL-C) and elevated triglycerides (TG) level. However,
      in diabetes mellitus, low density lipoprotein cholesterol (LDL-C) which is used
      as one of the markers for the risk of CVD, is underestimated so in such cases the
      levels of non-High density lipoprotein cholesterol (non-HDL-C) can be a stronger
      predictor of CVD as it strongly correlates with atherogenic lipoproteins.
      Therefore, an attempt has been made to evaluate the level of non-HDL-C as a newer
      marker for the risk of cardiovascular disease and to find out the pattern of
      dyslipidemia in diabetes mellitus. The present study comprised of 82 type 2
      Diabetic cases and 81 non-diabetic controls. Among the diabetics, the majority of
      the subjects (61.0%) were HDL-C dyslipidemic. However, among the controls, the
      maximum numbers of individuals (40.7%) were TG dyslipidemic. Diabetics have
      significantly elevated ratio of total cholesterol to high density lipoprotein
      cholesterol (TC/HDL-C) and the significant increased levels of non-high density
      lipoprotein cholesterol (non-HDL-C) compared to controls which can be used as
      markers of dyslipidemia and can also be used to predict the risk of
      cardiovascular disease in type 2 Diabetes Mellitus.

PMID- 24579535
TI  - Knowledge and practice of blood donation: a comparison between medical and non
      medical Nepalese students.
AB  - College students form a large and important group of population eligible for
      blood donation. Studies report that students do not donate much, and medical
      students' blood donation rate is less as compared to non-medical students. To
      assess and compare the knowledge, attitude, and practice of blood donation among
      medical and non-medical Nepalese students. A cross-sectional descriptive study
      using structured self-administered questionnaire was conducted in students of
      medical (MBBS) and non-medical programs of different colleges of Nepal. Total 456
      students, 177 non-medical and 279 medical, participated; 28.5% students were
      donors. More medical students donated blood, more often, and were more
      knowledgeable in all aspects of blood and blood donation related knowledge (p
      values 0.01 or less). In both groups, proportionately more boys donated than
      girls. Common reasons for not donating included no request, medically unfit, no
      information about blood collection services, fear of weakness, and fear related
      to venepuncture. Moral satisfaction was the commonest reason to donate. Among
      Nepalese students, medical students donate more and are more knowledgeable than
      non-medical students. Lack of information and lack of direct requests are
      important causes of fewer donors in the non-medical group and girls.

PMID- 24579536
TI  - Transthoracic echocardiography may be useful for preoperative cardiac evaluation
      of gynaecological patients undergoing routine surgery.
AB  - Echocardiography has been an integral noninvasive tool for [preoperative] cardiac
      evaluation that provides with echocardiographic details which may also be useful
      to perioperative clinicians to tailor their anesthetic deliberation while dealing
      with preoperative patients. The objective of this study is preoperative
      evaluation of routine gynecological patients echocardiographically after being
      referred from respective internists or anesthesiologists. This was a prospective,
      nonrandomized study of elective 68 cases who underwent echocardiographic
      evaluation preoperatively from 15th July 2009 to 14th July 2012. The mean age of
      the patients was 52.1 +/- 10.3 years with the age range of 30-79 years. Valvular
      heart disease was the most common echocardiographic finding (129.4%) followed by
      left ventricular diastolic dysfunction, LVDD (48.5%) and left ventricular
      hypertrophy (22.1%). Systolic dysfunction was detected in 2.9% of patients and
      pulmonary arterial hypertension in 2.9% patients. Amongst patients referred after
      preoperative anaesthetic evaluation, patients had different cardiac lesions
      echocardiographically. Preoperative echocardiographic evaluation may provide
      important cardiac informations and values which might be employed by
      perioperative physicians to tailor their treatment.

PMID- 24579537
TI  - Profile of neonates born to adolescent mothers at Nepal medical college teaching
      hospital.
AB  - Pregnancy in adolescence is often associated with maternal complications as well
      as preterm delivery, low birth weight babies and small for date babies. A
      retrospective study was carried out in 350 adolescent women who delivered child
      at Nepal Medical College Teaching Hospital (NMCTH), Attarkhel, Kathmandu from
      April 2005 to February 2009. Data were obtained from the case record register.
      Prevalence of pregnancy in adolescence was 11.1%. Majority of adolescent mother
      were aged between 17-19 years, belonging to Mongolian ethnicity, Hindu by belief
      and residing within Kathmandu Valley. More than 90.0% mothers were primigravida
      and 85.4% had complete antenatal check up (ANC). Normal vaginal delivery was the
      predominant mode of delivery (84.6%), followed by lower section caesarean section
      (LSCS) (14.0%) and instrumental delivery (1.1%). In newborn, male outnumbered
      female (59.7% versus 40.3%). A reasonable number of preterm (10.9%), low birth
      weight (12.3%), small for gestational age babies (7.4%) and neonates with birth
      asphyxia (10.3%) were noted. These newborns are often associated with high
      morbidity and mortality. Therefore, it is imperative to prevent teenage pregnancy
      by providing adequate access to health facilities and raising awareness about the
      sex and reproductive health amongst this population.

PMID- 24579538
TI  - Effect of posture on heart rate variability in school children.
AB  - Heart rate variability (HRV) refers to the beat-to-beat alteration in cardiac
      cycle length. The objective is to study effect of posture on HRV. Five minutes
      ECG of children (12 females and 20 males) with mean height 138.88 +/- 11.88 cm,
      weight 27.66 +/- 5.87 kg and BMI 16.11 +/- 1.38 kg/m(2) were recorded in supine,
      sitting and standing position. HRV parameters were compared by one-way ANOVA and
      Bonferroni test. Standing decreases Mean interval between successive RR waves
      (622.69 +/- 83.24 ms versus 721.66 +/- 89.30 ms versus 750.28 +/- 107.917, p <
      0.001), the square root of the mean squared differences of successive interval
      (25.37 +/- 17.52 ms versus 50.16 +/- 25.03 ms, p < 0.001), numbered of RR
      interval differences 50ms (40.59 +/- 61.58 versus 115.72 +/- 75.408 versus 134.16
      +/- 76.57, p < 0.001), percentage NN50 (9.65 +/- 15.32 versus 29.85 +/- 20.52,
      versus 36.18 +/- 22.33, p < 0.001), High frequency (HF) peak (152.63 +/- 254.41
      versus 427.84 +/- 369.62, 540.84 +/- 452.12, p < 0.05), HF power % (34.91 +/-
      17.67 versus 51.99 +/- 17.57 versus 56.94 +/- 17.06, p < 0.001), HF normalised
      unit (45.05 +/- 17.82 versus 61.11 +/- 17.06 versus 65.73 +/- 15.14, p < 0.001)
      as compared to sitting and supine. Standing increases low frequency (LF) power %
      (39.78 +/- 11.76 versus 31.64 +/- 12.33 versus 28.53 +/- 11.65, p < 0.05), LF
      normalized unit (54.95 +/- 17.82 versus 38.89 +/- 17.05 versus 34.27 +/- 15.14, p
      < 0.001), LF: HF ratio (1.61 +/- 1.26 versus 0.808 +/- 0.69 versus 0.63351 +/-
      0.538, p < 0.001) compared to sitting and supine. This study showed significant
      decreased in HRV parameters reflecting vagal activity and reciprocal increase in
      sympathetic activity in standing as compared to sitting and supine. There was no
      significant change in HRV in sitting as compared to supine.

PMID- 24579539
TI  - Prevalence of tuberculosis in household contacts of sputum smears positive cases
      and associated demographic risk factors.
AB  - Pulmonary tuberculosis (PTB) is transmitted by aerosolized droplets nuclei. Home
      is the vulnerable place for transmission of this disease to its contacts. Risk
      factors associated with this contact transmission may differ according to
      locality. This study aims to determine the prevalence of household contact (HC)
      PTB and examine the risk factors contributing to it. A cross-sectional study was
      conducted to determine the prevalence of HC TB among HCs aged > 5 years in
      Dharan. During the study period (June 2009 - May 2010), 184 index cases with
      sputum smear positive for AFB and their 802 HCs were included. Three sputum
      specimens were collected from each HCs and examined microscopically for AFB
      detection. The prevalence of HC TB was found to be 1.6%. The result was
      statistically associated (P < 0.05) with illiterate HCs (OR= 5.77, 95%CI =1.52
      21.81), close proximity with ICs (OR=3.07, 95%CI = 1.02-9.25), primary relatives
      to ICs (OR= 4.85, 95%CI = 1.07-22.05) and slum dweller (OR = 4.56, 95%CI = 1.25
      16.71). Similarly, AFB positivity was associated (P<0.05) with household crowding
      (OR = 7.46, 95%CI = 2.36-23.49), room size < or = 10 x 10 feet (OR=4.05, 95%CI =
      1.23-13.25), firewood user while cooking (OR = 5.96, 95%CI = 1.92-18.45). The
      prevalence of HCs tuberculosis is found to be 1.6%. Poverty, illiteracy,
      overcrowding, close proximity, close relation with ICs, firewood while cooking,
      slum dweller, are major factors highlighted by this study as risk factors of
      contact TB. Our results recommend a much better contact tracing and treatment
      program.

PMID- 24579540
TI  - Breast cancer knowledge and screening practice among women visited to KIST
      medical college.
AB  - Breast cancer is one of the most common cancers among female worldwide. Global
      statistics show the annual incidence of breast cancer is increasing and this is
      occurring more rapidly in countries with a low incidence rate of breast cancer.
      In Nepal it is second most common cancer after cervical cancer. Studies shows the
      mortality rate of breast cancer can be reduced by early detection and Screening
      program. According to the latest WHO data published in April 2011 breast cancer
      death in Nepal has reached 1,248 (0.84%) of total death. The age adjusted death
      rate is 12.92 per 1000,000 of population and the rank has been reached in number
      142 in the world. This study was aims to assess the knowledge and screening
      practice for breast cancer among women. A cross- sectional descriptive study was
      conducted among 110 women age range from 20 to 60 years at KIST Medical College,
      Imadol, Lalitpur. Purposive sampling technique was adopted. Structured
      questionnaire were used for data collection. Verbal informed concent was taken
      from each respondents. Descriptive analysis and simple statistical methods were
      used. Findings revealed that respondents who had heard about breast cancer were
      33 (30%) and not even heard were 77 (70%), out of them 26 respondents were doing
      regular screening which was breast self- examination by 19 (73%) mammography 3
      (11-5) and USG- 4 (15.4%). Their common source of information were Radio/TV. 90
      (81%) married women were 90 in numbers. Knowledge on risk factors of breast
      cancer was very low. Result of this study shows low knowledge on breast cancer,
      risk factors and screening practice among women groups of this study. Thus it is
      important to educate women about importance of early detection through screening
      methods for breast cancer to reduce mortality.

PMID- 24579541
TI  - Practices and attitudes towards tobacco use among the employees of a private
      organization in Nepal.
AB  - Tobacco use is considered as the symbol of adulthood and as a friend during
      stress and loneliness. It is an important part of Nepali society. With changing
      time trend, higher education, and awareness campaigns, people have become more
      conscious regarding tobacco use and its effects on health. Information and
      technology sector is considered one of the busiest sector. People are working at
      constant stress. Tobacco use is considered by many people as one of the ways for
      stress relief. A cross sectional study was conducted in a private organization.
      The main objective was to understand attitudes and practices of tobacco use among
      the employees. Among the participants 67% were males and 33% were females. Nearly
      95% of employees have experience of tobacco use in any form and 5% of participant
      reported as tobacco non user. Eighty one percent of the participants were
      smokers. More than half (52%) use tobacco for coping the stress and 4.3% use
      during brainstorming. Sixty seven percent were aware of the harmful effects of
      tobacco on health. Inspite of knowledge about harmful effect of tobacco use, it
      is still prevalent mostly among those who lead stressful life. So continuation
      and reform of various health education programmes with special target on
      behavioural changes is much needed.

PMID- 24579542
TI  - Common reasons for hospitalization among adult patients with diabetes in a
      private medical college in Kathmandu.
AB  - Diabetes Mellitus is one of the important non communicable disease affecting the
      adult populations around the world. Incidence of diabetes increasing in South
      Asia. Nepal is also experiencing increasing in diabetes disease burden. Diabetes
      mellitus is one of the important causes of hospital admission in the western
      world. In this study we evaluated the causes of hospital admission amongst
      diabetic population. Most common cause is of diagnosis is some forms of
      infections commonest (20%) being urinary tract infections. Ten out of total 69
      patients had septicemia. Six patients out of 69 had sputum positive pulmonary
      tuberculosis only one patient presented with metabolic complications of diabetes
      i.e. diabetic ketoacidosis. Coronary artery disease with heart failure was
      present in 14 patients. Five patients had diabetic nephropathy and 3 had
      retinopathy. This shows that infections is the major cause of hospital admission
      for diabetics followed by heart failure. Tuberculosis is important diagnosis in
      person with diabetes. This study shows more female patients get admitted and
      amongst admitted patents glycemic control is poor. This signify that women had
      more complications than male counter parts.

PMID- 24579543
TI  - Medico-social and behaviour problems amongst primary school children in rural
      area of Kathmandu, Nepal.
AB  - The objective of the study was medico- social and behaviour problems among
      primary school children of age (6-10 years) in rural area of Eastern part of
      Kathmandu Valley. Observational descriptive study was conducted in Govt. and
      Private Boarding Schools of rural Kathmandu Valley. Total 503 school children in
      primary school (6-10 years), Schools of rural area of Eastern part of Kathmandu,
      4 were randomly chosen by systematic random technique. All students aged 6-10
      years were included in the study. Complete data of each child was collected in a
      pre-designed, pre-tested questionnaire proforma. Out of 503 children, 230 (45.7%)
      boys and 273 (54.3%) were girls. Four hundred and thirteen (82.1%) children were
      found to be suffering from one or more morbid conditions. Hygienic condition was
      poor as in apparent look. Ninty nine (19.7%) respondents had lice and urticarial
      rashes in 47(9.3%), behaviour problems in 117 (23.3%), eye related diseases in 94
      (18.7%), ear diseases in 413 (82.1%) and dental carries in 130 (25.8%) as
      observed in the study. Diseases that are seen among the school children are
      mostly preventable and the health of the child can be improved by promotion of
      hygienic practices through proper health education by the teachers and parents.

PMID- 24579544
TI  - Outcome of pertrochantric fracture of the femur treated with proximal femoral
      locking compression plate.
AB  - Pertrochantric femoral fractures are one of the most common fracture in old
      patients with variety of complications. However fixing Pertrochantric femoral
      fractures properly is clinically challenging. We report the outcome of
      pertrochantric femoral fractures treated with Proximal Femoral Locking
      Compression Plate (PFLCP) using Minimal Invasive Percutaneous Plate
      Osteosynthesis (MIPPO) techniques which were evaluated clinically by Harris hip
      score and radiologically for a union at fracture site and implant related
      complication. The study included total of 33 patients (20 males and 13 females)
      with Pertrochantric femoral fractures. The mean ages of the patients were 57
      years (23-88 years). Pertrochantric femoral fractures included both
      Intertrochantric and Subtrochantric femoral fractures. Patients were followed up
      at 2 weeks, 6 weeks, 3 months, 6 months and 1 year after the operation. Among the
      33 patients, the union rate was 95% (31 patients). However there were 1 case of
      implant breakage and 1 case of non union. According to Harris Hip score the
      excellent and good results were 87.87% with no mortality during 1 year follow up
      period. The PFLCP can be feasible alternative to the treatment of Pertrochantric
      femoral fractures by providing biological healing and mechanical stability with
      limited occurrence of complications.

PMID- 24579545
TI  - Study on responses after splenectomy for idiopathic thrombocytopenic purpura
      patients, Kathmandu, Nepal.
AB  - Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disorder characterized
      by accelerated destruction of platelets due to the presence of platelet (Plt)
      auto antibodies and impaired production of platelets. Splenectomy is still the
      standard salvage therapy in cases refractory to corticosteroid therapy.
      Retrospectively we analyzed 34 patients with ITP that underwent splenectomy in
      the period May 2010 to March 2012 and have been followed for at least 12 months.
      All patients met the diagnostic criteria for ITP. The median age at diagnosis was
      26 years (range: 14-55 years). Overall response rate to splenectomy after 1 year
      of follow up was 94.1%, with Complete response in 32 and no response or relapse
      in 2 (5.8%). Sex didn't influence the outcome after splenectomy in our group of
      patients. Only preoperative response to steroids (P value = 0.018) and post
      operative platelet count (P value = 0.013) were found to be significant
      statistically. Splenectomy considered as safe and effective treatment for
      patients with ITP who failed to respond to firs-line treatment with
      corticosteroids. Management of patients who do not respond or relapse after
      splenectomy represent an important problem for further treatment due to low
      response rate to other treatment options.

PMID- 24579546
TI  - Sonographic assessment of placental migration in second trimester low lying
      placenta.
AB  - To assess the migration of low lying placenta diagnosed in the second trimester
      ultrasonogram (USG). All the women attending antenatal OPD clinic had undergone
      routine obstetric USG in the second trimester (14 weeks onwards). Those cases who
      had low lying placenta lower edge of placenta within 3.0 cms from the cervical
      internal os were included in the study. These cases were subjected to be followed
      up at 4 weekly interval to repeated serial ultrasonogram by Transabdominal and/or
      Transvaginal USG well through 3rd trimester of pregnancy or delivery which ever
      was earlier. Of the total 1229 second trimester USG, 312 (25.3%) women had low
      lying placenta in the second trimester. Follow up of this 312 cases indicated
      that in 288 (92.4%) cases it had migrated to upper segment by 3rd trimester. The
      migration of placenta was 92.4% and 68.0 % where the distance between the leading
      edge of placenta and cervical internal os was more than 2.0 cm or less than 2 cm
      respectively. Migration was not observed in women where the distance was less
      than 1.5 cm. Placental migration was 94.5% in anteriorly situated placenta and
      90.2% in posteriorly situated placenta. The rate of placental migration was
      95.1%, 77.7%, 55.5% in women who had previous normal delivery, previous caesarean
      delivery and prior history of dilatation and curettage (D & C) or manual removal
      of placenta (MRP), respectively. The prevalence of low lying placenta in 2nd
      trimester is 25.3%, which reduces to 7.3% at term. The rate of placental
      migration was over 90.0%. Factor like initial distance between the lower edge of
      the placental and cervical internal os. placental position and previous birth by
      caesarean section influence the placental migration.

PMID- 24579547
TI  - Color vision deficiency among a group of students of health sciences.
AB  - Color vision deficiency, most of the time remains an unnoticed problem; even many
      doctors/health professionals do not know the severity of their color vision
      deficiency and their disability. Some common difficulties reported by medical
      practitioners and students of health sciences were in recognizing- widespread
      body color changes (pallor, cyanosis, icterus, rashes, erythema of skin),
      colorful charts, slides, test-strips of blood and urine, body products: blood or
      bile in urine, faeces, sputum, vomitus, microscopy, oral and throat lesions,
      titration end-points, tissue identification (surgery) etc. The present study was
      undertaken to evaluate the presence of congenital color vision deficiency among
      the students of health sciences. The study was carried out among the medical and
      dental male students of Nepal Medical College and Teaching Hospital (n = 215)
      from November 2, 2012 to December 4, 2012 with the help of Ishihara chart which
      was shown to all male participants and were asked to read the impressions in the
      color chart. The impressions perceived by a person with normal color vision were
      different from the impressions perceived by a person with color vision
      deficiency. After careful screening, it was noted that among the study population
      (n = 215), 12 were color deficient (5.58% of our study population). Among them,
      one could not appreciate color (total color blindness according to the chart
      used), protanomaly was detected in 1, deuteranomaly in 3 and deuteranopia in 7
      volunteers. Students of health sciences must be made aware of their congenital
      color vision deficiency and its effects on their work. Screening enables the
      students and later the health professionals to become aware of limitations in
      their powers of observation and devise ways of overcoming them. The patient is
      protected from harm and legal action may be avoided when the health professional
      have adapted their practice to their deficiency. Medical/ dental students and
      health professionals must be screened for color vision deficiency and advised
      about it, so that they can take special care in clinical practice.

PMID- 24579548
TI  - Effect of exposure to radio frequency radiation emitted by cell phone on the
      developing dorsal root ganglion of chick embryo: a light microscopic study.
AB  - With an ever increasing number of cell phone users since late twentieth
      [corrected] century, magnitude of the problem of exposure to radiation emitted by
      cell phone is self evident. Extensive research had been devoted to incriminate or
      absolve it as a health hazard. Radiofrequency radiation emitted by cell phone had
      been stated to be a potent carcinogen, cytotoxic, genotoxic, mutagenic and
      neurobehavioral teratogen. Its effect on the brain had been a subject of
      extensive research evidently due to its proximity to the user's brain. While
      considering the biological effects of radiofrequency radiation, its intensity,
      frequency and the duration of exposure are important determinants. Nevertheless
      the results of these different studies have not been unequivocal. Considering the
      contradictory reports, the present work was undertaken to study the effect of
      such an exposure on the developing neural tissue of chick embryo. The processes
      of cell division and differentiation are fundamental to the development of any
      living being and are a sensitive index of any insult sustained at this stage.
      Neurons of dorsal root ganglion were selected for the present study as these
      ganglia were fully differentiated as early as fourth day of embryonic life. By
      varying duration of exposure, the embryos were exposed to different doses of
      radiation, sacrificed at different periods of incubation and subjected to
      histological processing. On light microscopic study it was observed that
      developing neurons of dorsal root ganglion suffered a damage which was dose
      dependent and persisted in spite of giving the exposure-free period between two
      exposures.

PMID- 24579549
TI  - Massive ascites in severe pre-eclampsia: a rare complication.
AB  - We report a rare case of massive maternal ascites complicating severe pre-
      eclampsia toxaemia (PET) seen in April 2013. This complication developed in
      association with the rise of blood pressure of 160/110 mmHg or more, worsening of
      proteinuria and hyperuricaemia. The onset of massive ascites caused respiratory
      compromise to the patient, thus necessitating immediate termination of pregnancy.

PMID- 24579551
TI  - Analysis of 24-hour monitoring of intraocular pressure in 1055 eyes.
AB  - PURPOSE: To investigate the clinical significance of 24-hour monitoring of
      intraocular pressure (IOP). METHODS: A total of 571 cases (1055 eyes) undergoing
      24-hour monitoring of IOP in the Second People's Hospital of Zhengzhou between
      June 2012 and March 2013 were retrospectively analyzed. RESULTS: Among all 1055
      eyes, 298 had suspected glaucoma (28.2%); 390 (37.0%) were diagnosed with
      glaucoma but received no treatment (312 with primary open angle glaucoma (POAG)
      and 78 with primary angle closure glaucoma (PACG)); 215 (20.4%) were diagnosed
      with glaucoma and received medical treatment; 132 (12.5%) underwent glaucoma
      filtration surgery; and there were 20 others. Through 24-hour IOP monitoring, 104
      among 298 cases with suspected glaucoma were diagnosed with normal tension
      glaucoma (NTG), 110 with POAG, and 28 with the secondary glaucoma. Condition
      assessment and treatment plans were presented for 390 glaucoma cases receiving no
      treatment. Adjustment was made in the medical treatment of 138 eyes. Following
      glaucoma filtration surgery, 52 eyes received clinical advice on subsequent
      treatment. CONCLUSION: The simplified 24-hour IOP monitoring method is readily
      accepted by patients, which is of great significance for providing guidance on
      the diagnosis of glaucoma and the assessment of the efficacy of glaucoma surgery.
      However, one-time 24-hour IOP monitoring is not sufficiently efficacious to make
      a definite diagnosis of NTG. Therefore, long-term follow-up and repeated 24-hour
      IOP monitoring are required to diagnose NTG, along with a variety of related
      examinations.

PMID- 24579550
TI  - Ten-year follow-up of familial nanophthalmos in three siblings.
AB  - PURPOSE: Nanophthalmos is a rare congenital disorder associated with a high
      incidence of angle-closure glaucoma. We followed the clinical manifestations of
      three siblings to evaluate their responses to various treatments. METHODS: Three
      sisters with nanophthalmos were followed from 2000 to 2013. Glaucoma and cataract
      treatments were performed whenever indicated. RESULTS: The oldest sister had
      chronic elevation of intraocular pressure (IOP) and underwent laser peripheral
      iridotomy (LPI) on both eyes, followed by uneventful phacoemulsification with
      intraocular lens (IOL) implantation on the left eye and phacotrabeculectomy with
      IOL implantation on the right eye. The middle sister had acute elevation of IOP
      and initially underwent phacoemulsification combined with implantation of two
      IOLs on her left eye and LPI on her right eye. Severe uveal effusion occurred
      when phacoemulsification was performed on her right eye 6 years later, but
      ultimately was completely resolved. In both sisters, stable IOP and visual
      results were achieved after lensectomy. The youngest sister, who had suspected
      angle-closure, achieved a stable IOP and visual results with prophylactic LPI
      alone. CONCLUSION: In nanophthalmic eyes, the severity of the disease may
      foreshadow the severity of surgical complications and responses to therapy.

PMID- 24579552
TI  - Clinical evaluation of traumatic ciliochoroidal detachment with surgical
      treatment.
AB  - PURPOSE: To determine the clinical features of traumatic ciliochoroidal
      detachment (CCD), and to evaluate the surgical outcomes. METHODS: We
      retrospectively reviewed the records of 37 consecutive patients with traumatic
      CCD who underwent surgical procedures, including ciliary body suturing,
      transscleral cyclophotocoagulation, and cyclocryopexy. A complete ocular
      examination was performed at pre-surgery and at periodical post-surgery follow
      ups. We compared visual acuity (VA), intraocular pressure (IOP), and morphologic
      changes with UBM among the different surgical procedures at the pre-surgery and
      periodical follow-ups. RESULTS: The mean IOP was 6.62 mmHg, and the median VA was
      20/200 at baseline. The mean final IOP was 11.03 mmHg, and the final median VA
      improved to 20/50. IOPs were significantly different in post-surgery compared
      with those at baseline (P = 0.000) among the ciliary body suturing,
      cyclophotocoagulation, and cyclocryopexy groups. However, no significant
      differences were noted at each follow-up among the 3 groups (P > 0.05). The post
      surgical morphological figures consisted of complete reattachment, partial
      reattachment, and the complete detachment. Cyclocryopexy (71.4%), suturing
      (68.4%), and cyclophotocoagulation (63.6%) produced similar surgical outcomes of
      the complete reattachment based on UBM images. CONCLUSION: Prompt treatment and
      periodic follow-ups are necessary after traumatic CCD, based on accurate
      dimensions and configuration by UBM. The appropriate choice of surgical
      procedures is pivotal for an optimal outcome.

PMID- 24579553
TI  - Evaluation of the consistency of total spherical aberration before and after
      aspherical intraocular lens implantation.
AB  - PURPOSE: To analyze the consistency between preoperatively estimated and
      postoperatively measured total spherical aberration and to evaluate the
      feasibility of personalized selection of an aspherical intraocular lens (IOL)
      based on the corneal spherical aberration measured by the Scheimpflug photography
      system (Pentacam). METHODS: A total of 47 patients (82 eyes) with age-related
      cataract received a comprehensive ophthalmologic examination. Corneal spherical
      aberration was measured by using the Scheimpflug photography system. Patients
      with corneal spherical aberration < or = 0.3 microm were implanted with a zero
      spherical aberration advanced optics (AO) aspherical intraocular lens and those
      with corneal spherical aberration > 0.3 microm received a Tecnis ZA9003
      aspherical lens (-0.27 microm spherical aberration). Preoperative total remnant
      spherical aberration was estimated and actual total spherical aberration was
      measured 3 months postoperatively. The consistency between preoperative and
      postoperative spherical aberration was analyzed by t-test, correlation analysis,
      and Blant-Altman plots. RESULTS: The estimated and measured values of total
      spherical aberration were (0.189 +/- 0.151) microm and (0.141 +/- 0.131) microm,
      with a statistical difference (t = 5.347, P < 0.01). For 45 eyes implanted with
      AO lenses, preoperatively estimated and postoperatively measured total spherical
      aberration were (0.268 +/- 0.137) microm and (0.214 +/- 0.103) microm. For 37
      eyes implanted with Tecnis ZA9003, preoperative estimate of total spherical
      aberration was (0.092 +/- 0.103) microm and postoperative measured value was
      (0.054 +/- 0.106) microm. Statistical significance was noted, as was a positive
      linear correlation between preoperative and postoperative values (gamma = 0.846,
      P < 0.01). Bland-Altman analysis showed high consistency between the estimated
      and measured spherical aberration. CONCLUSION: The estimated total spherical
      aberration measured preoperatively differed from the value measured
      postoperatively, but the two values showed good agreement. It is clinically
      feasible to conduct personalized selection of aspherical IOL based on Scheimpflug
      photography system (Pentacam) to measure corneal spherical aberration.

PMID- 24579554
TI  - Etiology and treatment of post-surgical blepharoptosis.
AB  - PURPOSE: To investigate the etiology and the treatment of acquired blepharoptosis
      inpatients, especially secondary to surgery. METHODS: The clinical records of 65
      consecutive patients with acquired ptosis were reviewed from an eye center and a
      comprehensive hospital. Potential factors responsible for acquired ptosis were
      investigated. Surgical management principles and post-operative exposure
      keratitis are discussed. RESULTS: The top three causes of acquired ptosis were
      postsurgical ptosis (20/65, 30.8%), traumatic ptosis (17/65, 26.2%) and senile
      aponeurotic ptosis (12/65, 18.5%). Twenty patients had post-surgical ptosis
      secondary to orbital surgery (8/20, 40.0%), enucleation and hydroxyapatite (HA)
      artificial eye implantation (4/20, 20%), eyelid surgery (3/20, 15%), cataract or
      glaucoma surgery (2/20, 10%), conjunctive surgery (2/20, 10%) and superior
      oblique muscle surgery (1/20, 5%). The levator palpebrae superioris (LPS) muscle
      of ten eyes (10/20, 50%) was found during exploration and reattached to the
      tarsal plate, with shortening of the LPS. Nine eyes (9/20, 45%) underwent a
      frontalis suspension (FS) operation because the LPS muscle was missing. One(1/20,
      5%) patient was not operated on due to a poor Bell's phenomenon. Two patients
      (2/65, 3.1%)--one patient with post-surgical ptosis and another with aponeurotic
      ptosis--developed exposure keratitis after ptosis correction. CONCLUSION: Post
      surgical ptosis is one of the most common causes of acquired ptosis. It is
      important to explore LPS muscle during surgery. LPS reattachment is performed if
      the muscle is found; otherwise, a FS operation is chosen. Exposure keratitis
      after correction should be monitored.

PMID- 24579555
TI  - Comparison of hematoxylin-eosin staining and methyl violet staining for
      displaying ghost cells.
AB  - PURPOSE: To compare the merits and limitations of hematoxylin-eosin (HE) and
      methyl violet staining for displaying ghost cells from vitreous or aqueous humor.
      METHODS: A specimen containing ghost cells was adjusted to five different
      concentrations: (12 x 10(4), 10 x 10(4), 8 x 10(4), 6 x 10(4) and 4 x 10(4)
      cells/ml) and subjected to smearing and methyl violet and HE staining. The
      staining results were observed by light microscopy. RESULTS: The ghost cells were
      readily observed at a cell density of > 8 x 10(4) cells/ml with methyl violet
      staining, but only a few cells were occasionally seen at lower cell densities. In
      contrast, ghost cells were seen at all cell densities with HE staining.
      CONCLUSION: Methyl violet staining is more rapid and simpler for the
      identification of ghost cells, but its staining color more readily fades, the
      slides cannot be stored, and it is only effective at a cell density of > 8 x
      10(4) cells/ml. In contrast, HE staining is more time-consuming but it can
      display cell morphology and distinguish cell components more explicitly and
      slides can be permanently stored. HE staining has advantages over methyl violet
      staining in detecting the ghost cells when the concentration is < 8 x 10(4)
      cells/ml.

PMID- 24579556
TI  - Genetic and phenotypic investigation of a Chinese pedigree with lattice corneal
      dystrophy IIIB subtype.
AB  - PURPOSE: To investigate phenotypes and disease-causing mutation in the
      transforming growth factor b-induced gene (TGFBI) in a Southern Chinese pedigree
      with lattice corneal dystrophy (LCD) IIIB with complicated cataract. METHODS: A
      Southern Chinese pedigree with lattice corneal dystrophy IIIB with complicated
      cataract was recruited. Comprehensive ophthalmic investigations were performed
      before and after cataract surgery of phacoemulsification and intraocular lens
      implantation in the proband's both eyes. Peripheral blood was collected from the
      proband, and genomic DNA was extracted. All exons of the TGFBI gene were
      sequenced to screen possible mutations. RESULTS: A bilateral LCD IIIB subtype was
      observed in the proband. Optical coherence tomography further revealed
      superreflective changes in the subepithelial and stroma layers of the cornea,
      with reduced central corneal thickness. Notably, bilateral cataract was found in
      the proband. Direct sequencing detected a recurrent heterozygous missense c.1877A
      > G mutation in exon 14 of the TGFBI gene, resulting in substitution of histidine
      with arginine (p.H626R). CONCLUSION: The current study was the first report of
      the TGFBI p.H626R mutation in Southern Chinese, suggesting that it could be a
      mutation hotspot across populations. Moreover, the mutation was associated with
      LCD IIIB subtype with complicated cataract, which had not been reported before,
      pointing to clinical heterogeneity of the mutation.

PMID- 24579557
TI  - Expression of Netrin-1 in diabetic rat retina.
AB  - PURPOSE: To detect the expression of Netrin-1 in the retinas of diabetic rats and
      evaluate the relationship between Netrin-1 mRNA and diabetic retinopathy (DR).
      METHODS: Twenty healthy adult male Sprague-Dawley (SD) rats were randomly divided
      into a diabetic model group (DM) and a normal control group (NC), each group was
      composed of ten rats. Sreptozocin (STZ) was administered intraperitoneally at a
      single dose of 60 mg/kg to diabetic group. The control rats were injected only
      with citrate buffer. Collection of serum at 72 h after STZ treatment and
      measuring blood glucose levels confirmed the development of diabetes. The rats
      with blood glucose level 16.67 mmol/L or higher were considered to be diabetic
      and were used in the experiment. Retinal tissues were harvested and expression of
      netrin-1 mRNA and protein in the retina tissues was examined by reverse
      transcription polymerase chain reaction (RT-PCR) and western blot analysis,
      respectively. RESULTS: Diabetic rats showed classic symptoms of diabetes
      mellitus, such as polydipsia, polyphagia, and polyuria. Cataract was seen in the
      DM group at 3 months after administration of STZ. Both netrin-1 mRNA and protein
      levels retina were dramatically increased in the DM rats compared to the NC group
      (P < 0.05). CONCLUSION: Diabetic rats can be successfully established by
      intraperitoneal injection of streptozotocin (60 mg/kg). Netrin-1 may play an
      important role during the development of diabetic retinopathy.

PMID- 24579558
TI  - Iridocorneal endothelial syndrome in a Chinese child.
AB  - PURPOSE: We reported a rare case of ICE syndrome in a Chinese child. CASE REPORT:
      A 6-year-old child was admitted to the ophthalmology department of the Affiliated
      Wuxi Second Hospital of Nanjing Medical University, complaining of elevated
      intraocular pressure at his first diagnosis in a local hospital. The patient was
      initially treated with medication. During subsequent follow up, two iris holes
      were seen in the patient's right eye and he was then diagnosed with ICE syndrome.
      The child underwent surgery combined with mitomycin C intraoperatively. The
      intraocular pressure was stably controlled. CONCLUSION: ICE syndrome has been
      rarely reported in children. Glaucoma filtering surgery combined with
      intraoperative administration of mitomycin is efficacious for intraocular
      pressure control.

PMID- 24579559
TI  - Progress in screening and treatment of common congenital eye diseases.
AB  - Congenital eye illnesses are caused by congenital ocular malformations and are a
      primary cause of poor visual acuity and blindness in infants. Early diagnosis and
      treatment of congenital eye illnesses are of great significance for affected
      infants, their families, and even society as a whole. This study describes the
      current situation for prenatal and infant screening for congenital eye diseases
      and briefly summarizes novel progress in the treatment of the five most common
      eye diseases (congenital dacryocystitis, congenital cataract, retinopathy of
      prematurity, congenital glaucoma and retinoblastoma). Current programs are now
      aimed at improvements in the prevention and treatment of congenital eye diseases
      in China.

PMID- 24579560
TI  - Infection control after surgical management of complex retinal detachment by
      vitrectomy.
AB  - PURPOSE: To investigate the risk factors and infection control after vitrectomy.
      METHODS: By analyzing the risk factors of surgical infection following
      vitrectomy, a sound surgical cooperation workflow was established. A system of
      equipment cleaning, disinfection, and quarantine was set up. The use of sterile
      implants and disposable consumables was subject to strict management and the
      system of operation room environment and sterile technique were strengthened.
      RESULTS: Infection control during perioperative period was improved and the
      nursing staffs perceptions of preventing surgical infection were enhanced, which
      guaranteed the safety of vitrectomy and controlled the infection rate to levels
      as low as 0.035%. CONCLUSION: Proper management of vitrectomy plays a pivotal
      role in the prevention of post-vitrectomy surgical infection.

PMID- 24579561
TI  - EEG signals classification of epileptic patients via feature selection and voting
      criteria in intelligent method.
AB  - Epileptic disease can be diagnosed by using intelligent methods on the
      Electroencephalograph (EEG) signals. In this paper, wavelet packet transform
      (WPT) was used in each of the frequency bands and wavelet coefficients were
      obtained, then the energy and entropy function was done on the wavelet
      coefficients and used as initial feature vectors. In the next step, eight and 15
      features from 30 initial energy and entropy features were selected as the final
      features because their receiver operating characteristic (ROC) curve areas were
      higher than others. There were seven classifier inputs. These seven classifiers
      consisted of four artificial neural networks (ANN) with different structures,
      support vector machines (SVM), K-nearest neighbours (KNN) and a hybrid network.
      Each classifier was trained by 0.5, 0.8 and 0.9 EEG signals. After the training
      process, a fusion network based on a voting criteria was used to make the
      algorithm robust against the possible changes in each classifier and increase the
      classification accuracy. Finally, the algorithm was tested by other EEG signals.
      As a result, normal and epileptic classes were detected with total classification
      accuracy of 99-100%.

PMID- 24579563
TI  - Lateral preferences for hand clasping and arm folding are associated with
      handedness in two large-sample latent variable analyses.
AB  - Hand clasping (HC) and arm folding (AF) are bilateral limb postures which are
      subject to lateral preferences. Previous research suggested that left HC and left
      AF are "canonical" among European populations, i.e., generally preferred by right
      handers. However, evidence on the associations of handedness with HC and AF to
      date is sparse and inconsistent, with studies mostly relying on relatively small
      sample sizes and arbitrary classifications of handedness. Utilizing latent class
      analysis for handedness classification, we present data from two large and
      independent middle-European samples, a discovery (n = 7,658) and replication (n =
      5,062) sample. Our results indicate that right HC, not left HC, is overall
      preferred and that right-handedness is associated with right HC/left AF, and left
      and mixed-handedness with left HC/right AF. Moreover, lateral preferences
      increased with age, and men had a higher preference of right HC, independent of
      handedness. We discuss our findings with regard to the generalizability of
      previous results. 

PMID- 24579562
TI  - Prevalence of exertional rhabdomyolysis in endurance horses in the Pacific
      Northwestern United States.
AB  - REASONS FOR PERFORMING STUDY: Exertional rhabdomyolysis (ER) is a reported
      syndrome in competing endurance horses; however, the prevalence and cause of ER
      in this population have not been defined. OBJECTIVES: To determine the prevalence
      of ER in a sample of endurance racing horses and investigate factors, including
      relevant genetic defects, contributing to the occurrence of rhabdomyolysis in
      this group. STUDY DESIGN: Prospective clinical study. METHODS: Riders of 101
      horses participating in one of four 50-mile (80.5 km) distance races completed a
      comprehensive questionnaire regarding the medical history, management and
      performance of their horse. Serum creatine kinase activity (CK) was measured
      before and 4 h after completion of exercise. Hair samples were analysed by PCR
      for the R309H mutation in the glycogen synthase gene (GYS1) responsible for type
      1 polysaccharide storage myopathy (PSSM) and the C7360G mutation in the ryanodine
      receptor 1 (RYR1) gene causing malignant hyperthermia (MH). RESULTS: Samples were
      obtained from 68 Arabians, 20 half-Arabians and 13 horses of other breeds. Serum
      CK was above the resting reference interval (145-633 u/l) in 38 horses after
      racing (median 883 u/l, range 658-3739) but was compatible with values previously
      reported in apparently healthy endurance horses. Pathological ER was suspected to
      occur in 4 horses with serum CK activities exceeding 10,000 u/l 4 h after racing
      (median 84,825 u/l; range 10,846-381,790) including 3 Arabians and one half
      Arabian horse. GYS1 and RYR1 mutations were not present in hair samples from any
      horses. CONCLUSIONS: Exertional rhabdomyolysis occurred at a prevalence of 4.0%
      in a sample of horses participating in 50 mile distance events and all affected
      horses were Arabian or half-Arabian. The cause of ER in the endurance horse
      population remains unknown; however, ER in competing Arabian endurance horses is
      unlikely to be due to type 1 PSSM or MH.

PMID- 24579564
TI  - Series of new beta-cyclodextrin-cored starlike carriers for gene delivery.
AB  - The development of safe and effective beta-cyclodextrin (beta-CD)-cored cationic
      star gene carriers has attracted considerable attention. In this work, a series
      of star-shaped hemocompatible CD-PGPP, CD-PGAEPP, and CD-PGAPP vectors composed
      of beta-CD cores and piperazine (PP)-, N-(aminoethyl)piperazine (AEPP)-, or N-(3
      aminopropyl)-2-pyrrolidinone (APP)-functionalized poly(glycidyl methacrylate)
      arms were successfully proposed and compared for highly efficient gene delivery.
      Such star carriers possess plentiful secondary amine, tertiary amine, and
      nonionic hydroxyl groups. CD-PGPP, CD-PGAEPP, and CD-PGAPP were effective in
      condensing plasmid DNA into nanoparticles, whose sizes were 100-200 nm and
      positive zeta potentials were 25-40 mV at nitrogen/phosphate (N/P) ratios of 10
      and above. CD-PGPP, CD-PGAEPP, and CD-PGAPP showed significantly lower
      cytotoxicity than control poly(ethylenimine) (PEI; ~25 kDa). At most N/P ratios,
      CD-PGAPP exhibited better gene transfection performance than CD-PGPP and CD
      PGAEPP particularly in HepG2 cells. More importantly, in comparison with PEI, all
      of the CD-PGPP, CD-PGAEPP, and CD-PGAPP vectors did not cause undesirable
      hemolysis. 

PMID- 24579566
TI  - Evaluation of the "let's talk" safer sex intervention in Nepal.
AB  - This study is an evaluation of a pilot of the Let's Talk Intervention for Nepali
      women for effectiveness in increasing sexual health communication between women
      and the men in their lives. The intervention included 88 women in Kathmandu and
      spanned three 2-hour group sessions. Baseline, posttest, and follow-up knowledge,
      attitude, and behavior surveys were completed. Results showed women at posttest
      and follow-up spoke with more women and men about sex than they had at baseline.
      Attitudes regarding gender norms about sex improved as a result of the
      intervention, and shame about sex and sexuality for women decreased after
      intervention. Women also reported greater comfort discussing sex after the
      intervention. HIV knowledge scores increased after intervention but dropped again
      at follow-up, likely because of time constraints in addressing this topic in
      sufficient detail. This is the first program in Nepal that addresses
      communication about sexual health while focusing on education and prevention for
      HIV/STIs for women. 

PMID- 24579565
TI  - A straightforward strategy toward large BN-embedded pi-systems: synthesis,
      structure, and optoelectronic properties of extended BN heterosuperbenzenes.
AB  - A straightforward strategy has been used to construct large BN-embedded pi
      systems simply from azaacenes. BN heterosuperbenzene derivatives, the largest BN
      heteroaromatics to date, have been synthesized in three steps. The molecules
      exhibit curved pi-surfaces, showing two different conformations which are self
      organized into a sandwich structure and further packed into a pi-stacking column.
      The assembled microribbons exhibit good charge transport properties and
      photoconductivity, representing an important step toward the optoelectronic
      applications of BN-embedded aromatics. 

PMID- 24579567
TI  - Development of environmentally friendly messages to promote longer durations of
      breastfeeding for already breastfeeding mothers.
AB  - Durations of breastfeeding activity in the United States fall short of
      established recommendations by leading public health institutions. In response to
      this problem, this study sought to develop environmentally friendly messages to
      promote continued breastfeeding for moms already breastfeeding in order to help
      them reach recommended breastfeeding durations. Messages were successfully
      cultivated to encourage moms already breastfeeding to meet recommended
      breastfeeding durations. In addition, this study cultivated strategies by which
      to use environmentally friendly messages to urge mothers who still need to decide
      whether to breastfeed or formula feed to breastfeed, although this was not the
      purpose of the research. Avenues for future communication-based breastfeeding
      research were also elucidated. The Elaboration Likelihood Model serves as useful
      theory to assess the role of environmentally friendly messages in the promotion
      of continued breastfeeding. 

PMID- 24579568
TI  - Probing the force-induced dissociation of aptamer-protein complexes.
AB  - Aptamers are emerging as powerful synthetic bioreceptors for fundamental
      research, diagnostics, and therapeutics. For further advances, it is important to
      gain a better understanding of how aptamers interact with their targets. In this
      work, we have used magnetic force-induced dissociation experiments to study the
      dissociation process of two different aptamer-protein complexes, namely for hIgE
      and Ara h 1. The measurements show that both complexes exhibit dissociation with
      two distinct regimes: the dissociation rate depends weakly on the applied force
      at high forces but depends stronger on force at low forces. We attribute these
      observations to the existence of at least one intermediate state and at least two
      energy barriers in the aptamer-protein interaction. The measured spontaneous
      dissociation rate constants were validated with SPR using both Biacore and fiber
      optic technology. This work demonstrates the potential of the magnetic force
      induced dissociation approach for an in-depth study of the dissociation kinetics
      of aptamer-protein bonds, which is not possible with SPR technologies. The
      results will help in the development and expansion of aptamers as bioaffinity
      probes. 

PMID- 24579570
TI  - Attractive inverse square potential, U(1) gauge, and winding transitions.
AB  - The inverse square potential arises in a variety of different quantum phenomena,
      yet notoriously it must be handled with care: it suffers from pathologies rooted
      in the mathematical foundations of quantum mechanics. We show that its recently
      studied conformality breaking corresponds to an infinitely smooth winding
      unwinding topological transition for the classical statistical mechanics of a one
      dimensional system: this describes the tangling or untangling of floppy polymers
      under a biasing torque. When the ratio between torque and temperature exceeds a
      critical value the polymer undergoes tangled oscillations, with an extensive
      winding number. At lower torque or higher temperature the winding number per unit
      length is zero. Approaching criticality, the correlation length of the order
      parameter-the extensive winding number-follows a Kosterlitz-Thouless-type law.
      The model is described by the Wilson line of a (0+1) U(1) gauge theory, and
      applies to the tangling or untangling of floppy polymers and to the winding or
      diffusing kinetics in diffusion-convection reactions. 

PMID- 24579569
TI  - Maintenance therapy in newly diagnosed multiple myeloma: current recommendations.
AB  - The recent availability of novel agents has substantially improved the outcomes
      of patients with Multiple Myeloma (MM). Achieving the deepest level of complete
      response and maintaining a sustained remission are important steps towards MM
      cure. To achieve this goal, consolidation and maintenance therapies are currently
      incorporated into the modern therapeutic paradigm. The excellent activity shown
      by new drugs has led to their investigational use as maintenance therapy.
      However, despite promising results of continuous treatment with the novel agents,
      consensus regarding maintenance therapy still lacks. This review will focus on
      maintenance therapy, offering an overview of the different strategies available
      in MM. The issue of continuous treatment in the light of new biological
      discoveries, including intra-clonal heterogeneity, will also be addressed. 

PMID- 24579571
TI  - Distillation of the two-mode squeezed state.
AB  - We experimentally demonstrate entanglement distillation of the two-mode squeezed
      state obtained by parametric down-conversion. Applying the photon annihilation
      operator to both modes, we raise the fraction of the photon-pair component in the
      state, resulting in the increase of both squeezing and entanglement by about 50%.
      Because of the low amount of initial squeezing, the distilled state does not
      experience significant loss of Gaussian character. 

PMID- 24579572
TI  - Fermi condensation near van Hove singularities within the Hubbard model on the
      triangular lattice.
AB  - The proximity of the Fermi surface to van Hove singularities drastically enhances
      interaction effects and leads to essentially new physics. In this work we address
      the formation of flat bands ("Fermi condensation") within the Hubbard model on
      the triangular lattice and provide a detailed analysis from an analytical and
      numerical perspective. To describe the effect we consider both weak-coupling and
      strong-coupling approaches, namely the renormalization group and dual fermion
      methods. It is shown that the band flattening is driven by correlations and is
      well pronounced even at sufficiently high temperatures, of the order of 0.1-0.2
      of the hopping parameter. The effect can therefore be probed in experiments with
      ultracold fermions in optical lattices. 

PMID- 24579573
TI  - Suppressing the loss of ultracold molecules via the continuous quantum Zeno
      effect.
AB  - We investigate theoretically the suppression of two-body losses when the on-site
      loss rate is larger than all other energy scales in a lattice. This work
      quantitatively explains the recently observed suppression of chemical reactions
      between two rotational states of fermionic KRb molecules confined in one
      dimensional tubes with a weak lattice along the tubes [Yan et al., Nature
      (London) 501, 521 (2013)]. New loss rate measurements performed for different
      lattice parameters but under controlled initial conditions allow us to show that
      the loss suppression is a consequence of the combined effects of lattice
      confinement and the continuous quantum Zeno effect. A key finding, relevant for
      generic strongly reactive systems, is that while a single-band theory can
      qualitatively describe the data, a quantitative analysis must include multiband
      effects. Accounting for these effects reduces the inferred molecule filling
      fraction by a factor of 5. A rate equation can describe much of the data, but to
      properly reproduce the loss dynamics with a fixed fillingfraction for all lattice
      parameters we develop a mean-field model and benchmark it with numerically
      exacttime-dependent density matrix renormalization group calculations.

PMID- 24579574
TI  - Observing Dirac's classical phase space analog to the quantum state.
AB  - In 1945, Dirac attempted to develop a "formal probability" distribution to
      describe quantum operators in terms of two noncommuting variables, such as
      position x and momentum p [Rev. Mod. Phys. 17, 195 (1945)]. The resulting
      quasiprobability distribution is a complete representation of the quantum state
      and can be observed directly in experiments. We measure Dirac's distribution for
      the quantum state of the transverse degree of freedom of a photon by weakly
      measuring transverse x so as to not randomize the subsequent p measurement.
      Furthermore, we show that the distribution has the classical-like feature that it
      transforms (e.g., propagates) according to Bayes' law.

PMID- 24579575
TI  - Quantum graphs whose spectra mimic the zeros of the Riemann zeta function.
AB  - One of the most famous problems in mathematics is the Riemann hypothesis: that
      the nontrivial zeros of the Riemann zeta function lie on a line in the complex
      plane. One way to prove the hypothesis would be to identify the zeros as
      eigenvalues of a Hermitian operator, many of whose properties can be derived
      through the analogy to quantum chaos. Using this, we construct a set of quantum
      graphs that have the same oscillating part of the density of states as the
      Riemann zeros, offering an explanation of the overall minus sign. The smooth part
      is completely different, and hence also the spectrum, but the graphs pick out the
      low-lying zeros. 

PMID- 24579576
TI  - No-go theorem for the composition of quantum systems.
AB  - Building on the Pusey-Barrett-Rudolph theorem, we derive a no-go theorem for a
      vast class of deterministic hidden-variables theories, including those consistent
      on their targeted domain. The strength of this result throws doubt on seemingly
      natural assumptions (like the "preparation independence" of the Pusey-Barrett
      Rudolph theorem) about how "real states" of subsystems compose for joint systems
      in nonentangled states. This points to constraints in modeling tensor-product
      states, similar to constraints demonstrated for more complex states by the Bell
      and Bell-Kochen-Specker theorems. 

PMID- 24579577
TI  - Self-correcting quantum memories beyond the percolation threshold.
AB  - We analyze several high dimensional generalizations of the toric code at a
      nonzero temperature. We find that in a large enough dimension, there can be a
      distinct separation between the critical temperature Tc, given by thermodynamic
      singularities, and the percolation temperature Tp, given by the percolation of
      defects. We argue that the regime Tp<T<Tc is a range of temperatures where a self
      correcting quantum memory can operate despite having percolating defects. We
      present analytic arguments and numerical evidence in support of this scenario,
      including a mean-field treatment and Monte Carlo simulations. Near Tc,
      simulations observe a large hysteretic behavior, which may have applications by
      allowing the self-correcting phase to survive in a "superheated" regime. 

PMID- 24579578
TI  - Entanglement genesis by ancilla-based parity measurement in 2D circuit QED.
AB  - We present an indirect two-qubit parity meter in planar circuit quantum
      electrodynamics, realized by discrete interaction with an ancilla and a
      subsequent projective ancilla measurement with a dedicated, dispersively coupled
      resonator. Quantum process tomography and successful entanglement by measurement
      demonstrate that the meter is intrinsically quantum nondemolition. Separate
      interaction and measurement steps allow the execution of subsequent data-qubit
      operations in parallel with ancilla measurement, offering time savings over
      continuous schemes. 

PMID- 24579579
TI  - Laser damage helps the eavesdropper in quantum cryptography.
AB  - We propose a class of attacks on quantum key distribution (QKD) systems where an
      eavesdropper actively engineers new loopholes by using damaging laser
      illumination to permanently change properties of system components. This can turn
      a perfect QKD system into a completely insecure system. A proof-of-principle
      experiment performed on an avalanche photodiode-based detector shows that laser
      damage can be used to create loopholes. After ~1  W illumination, the detectors'
      dark count rate reduces 2-5 times, permanently improving single-photon counting
      performance. After ~1.5  W, the detectors switch permanently into the linear
      photodetection mode and become completely insecure for QKD applications. 

PMID- 24579580
TI  - Quantum search on graphene lattices.
AB  - We present a continuous-time quantum search algorithm on a graphene lattice. This
      provides the sought-after implementation of an efficient continuous-time quantum
      search on a two-dimensional lattice. The search uses the linearity of the
      dispersion relation near the Dirac point and can find a marked site on a graphene
      lattice faster than the corresponding classical search. The algorithm can also be
      used for state transfer and communication. 

PMID- 24579581
TI  - Quantum quenches and work distributions in ultralow-density systems.
AB  - We present results on quantum quenches in lattice systems with a fixed number of
      particles in a much larger number of sites. Both local and global quenches in
      this limit generically have power-law work distributions ("edge singularities").
      We show that this regime allows for large edge singularity exponents beyond that
      allowed by the constraints of the usual thermodynamic limit. This large-exponent
      singularity has observable consequences in the time evolution, leading to a
      distinct intermediate power-law regime in time. We demonstrate these results
      first using local quantum quenches in a low-density Kondo-like system, and
      additionally through global and local quenches in Bose-Hubbard, Aubry-Andre, and
      hard-core boson systems at low densities. 

PMID- 24579582
TI  - Scaling quasistationary states in long-range systems with dissipation.
AB  - Hamiltonian systems with long-range interactions give rise to long-lived out-of
      equilibrium macroscopic states, so-called quasistationary states. We show here
      that, in a suitably generalized form, this result remains valid for many such
      systems in the presence of dissipation. Using an appropriate mean-field kinetic
      description, we show that models with dissipation due to a viscous damping or due
      to inelastic collisions admit "scaling quasistationary states," i.e., states that
      are quasistationary in rescaled variables. A numerical study of one-dimensional
      self-gravitating systems confirms the relevance of these solutions and gives
      indications of their regime of validity in line with theoretical predictions. We
      underline that the velocity distributions never show any tendency to evolve
      towards a Maxwell-Boltzmann form. 

PMID- 24579583
TI  - Pseudolikelihood decimation algorithm improving the inference of the interaction
      network in a general class of Ising models.
AB  - In this Letter we propose a new method to infer the topology of the interaction
      network in pairwise models with Ising variables. By using the pseudolikelihood
      method (PLM) at high temperature, it is generally possible to distinguish between
      zero and nonzero couplings because a clear gap separate the two groups. However
      at lower temperatures the PLM is much less effective and the result depends on
      subjective choices, such as the value of the l1 regularizer and that of the
      threshold to separate nonzero couplings from null ones. We introduce a decimation
      procedure based on the PLM that recursively sets to zero the less significant
      couplings, until the variation of the pseudolikelihood signals that relevant
      couplings are being removed. The new method is fully automated and does not
      require any subjective choice by the user. Numerical tests have been performed on
      a wide class of Ising models, having different topologies (from random graphs to
      finite dimensional lattices) and different couplings (both diluted ferromagnets
      in a field and spin glasses). These numerical results show that the new algorithm
      performs better than standard PLM. 

PMID- 24579584
TI  - Annihilation of colliding Bogoliubov quasiparticles reveals their Majorana
      nature.
AB  - The single-particle excitations of a superconductor are coherent superpositions
      of electrons and holes near the Fermi level, called Bogoliubov quasiparticles.
      They are Majorana fermions, meaning that pairs of quasiparticles can annihilate.
      We calculate the annihilation probability at a beam splitter for chiral quantum
      Hall edge states, obtaining a 1+/-cosphi dependence on the phase difference phi
      of the superconductors from which the excitations originated (with the +/- sign
      distinguishing singlet and triplet pairing). This provides for a nonlocal
      measurement of the superconducting phase in the absence of any supercurrent. 

PMID- 24579585
TI  - Observation of the spatial distribution of gravitationally bound quantum states
      of ultracold neutrons and its derivation using the Wigner function.
AB  - Ultracold neutrons (UCNs) can be bound by the potential of terrestrial gravity
      and a reflecting mirror. The wave function of the bound state has characteristic
      modulations. We carried out an experiment to observe the vertical distribution of
      the UCNs above such a mirror at the Institut Laue-Langevin in 2011. The observed
      modulation is in good agreement with that prediction by quantum mechanics using
      the Wigner function. The spatial resolution of the detector system is estimated
      to be 0.7  MUm. This is the first observation of gravitationally bound states of
      UCNs with submicron spatial resolution. 

PMID- 24579586
TI  - Significant enhancement of neutralino dark matter annihilation from electroweak
      bremsstrahlung.
AB  - Indirect searches for the cosmological dark matter have become ever more
      competitive during the past years. Here, we report the first full calculation of
      leading electroweak corrections to the annihilation rate of supersymmetric
      neutralino dark matter. We find that these corrections can be huge, partially due
      to contributions that have been overlooked so far. Our results imply a
      significantly enhanced discovery potential of this well motivated dark matter
      candidate with current and upcoming cosmic ray experiments, in particular for
      gamma rays and models with somewhat small annihilation rates at the tree level. 

PMID- 24579587
TI  - Energy-energy correlations in n=4 supersymmetric Yang-Mills theory.
AB  - We present a new approach to computing energy-energy correlations in gauge
      theories that exploits their relation to correlation functions and bypasses the
      use of scattering amplitudes. We illustrate its power by calculating energy
      energy correlations in the maximally supersymmetric Yang-Mills theory in the next
      to-leading order approximation. 

PMID- 24579588
TI  - Holographic lattices give the graviton an effective mass.
AB  - We discuss the dc conductivity of holographic theories with translational
      invariance broken by a background lattice. We show that the presence of the
      lattice induces an effective mass for the graviton via a gravitational version of
      the Higgs mechanism. This allows us to obtain, at leading order in the lattice
      strength, an analytic expression for the dc conductivity in terms of the size of
      the lattice at the horizon. In locally critical theories this leads to a power
      law resistivity that is in agreement with an earlier field theory analysis of
      Hartnoll and Hofman. 

PMID- 24579589
TI  - All-order renormalization of the propagator matrix for fermionic systems with
      flavor mixing.
AB  - We consider a mixed system of Dirac fermions in a general parity-nonconserving
      theory and renormalize the propagator matrix to all orders in the pole scheme, in
      which the squares of the renormalized masses are identified with the complex pole
      positions and the wave-function renormalization (WFR) matrices are adjusted in
      compliance with the Lehmann-Symanzik-Zimmermann reduction formalism. We present
      closed analytic all-order expressions and their expansions through two loops for
      the renormalization constants in terms of the scalar, pseudoscalar, vector, and
      pseudovector parts of the unrenormalized self-energy matrix, which is computable
      from the one-particle-irreducible Feynman diagrams of the flavor transitions. We
      identify residual degrees of freedom in the WFR matrices and propose an
      additional renormalization condition to exhaust them. We then explain how our
      results may be generalized to the case of unstable fermions, in which we
      encounter the phenomenon of WFR bifurcation. In the special case of a solitary
      unstable fermion, the all-order-renormalized propagator is presented in a
      particularly compact form. 

PMID- 24579590
TI  - Violation of geometric scaling in deep inelastic scattering due to Coulomb
      corrections.
AB  - We compute the Coulomb correction to the total and diffractive cross sections for
      virtual photon scattering off a heavy nucleus at low x. We show that it violates
      the geometric scaling in a wide range of photon virtualities and is weakly x
      independent. In heavy nuclei at low Q2, the Coulomb correction to the total and
      diffractive cross sections is about 20% and 40%, correspondingly. 

PMID- 24579592
TI  - Stimulated Compton scattering in two-color ionization of hydrogen with keV
      electromagnetic fields.
AB  - We present a theoretical study of two-color ionization of hydrogen with keV
      photons at intensities ranging from 1016 to 1018  W/cm2. We consider the atom in
      interaction with a superposition of two electromagnetic pulses centered around
      two frequencies that differ by a few atomic units and we present in detail the
      case of the frequencies 55 and 50 a.u. We present the electron energy spectra,
      angular distributions, and ionization rates based on nonperturbative and
      perturbative calculations. Although the ejected electron energy distribution is
      dominated by one-photon ionization from each pulse, we are able to identify the
      contribution of stimulated Compton scattering, a process in which one photon is
      absorbed while the other is emitted, the photon energy difference being
      transferred to the electron. This leads to low-energy electrons, and we show in
      particular that it is of crucial importance to consider the retardation effects
      on the ionization rates and the electron angular distributions. The relative
      propagation direction of the two fields also plays an important role; in the case
      of counterpropagating fields, the ionization by stimulated Compton scattering is
      dominated by A2 and competes with one-photon ionization at high intensities. 

PMID- 24579591
TI  - Nuclear deformation and neutron excess as competing effects for dipole strength
      in the pygmy region.
AB  - The electromagnetic dipole strength below the neutron-separation energy has been
      studied for the xenon isotopes with mass numbers A=124, 128, 132, and 134 in
      nuclear resonance fluorescence experiments using the gammaELBE bremsstrahlung
      facility at Helmholtz-Zentrum Dresden-Rossendorf and the HIgammaS facility at
      Triangle Universities Nuclear Laboratory Durham. The systematic study gained new
      information about the influence of the neutron excess as well as of nuclear
      deformation on the strength in the region of the pygmy dipole resonance. The
      results are compared with those obtained for the chain of molybdenum isotopes and
      with predictions of a random-phase approximation in a deformed basis. It turned
      out that the effect of nuclear deformation plays a minor role compared with the
      one caused by neutron excess. A global parametrization of the strength in terms
      of neutron and proton numbers allowed us to derive a formula capable of
      predicting the summed E1 strengths in the pygmy region for a wide mass range of
      nuclides. 

PMID- 24579593
TI  - Quantum effects in double ionization of argon below the threshold intensity.
AB  - So far, nonsequential double ionization (NSDI) of atoms can be well understood
      within a semiclassical or even classical picture. No quantum effect appears to be
      required to explain the data observed. We theoretically study electron
      correlation resulting from NSDI of argon in a low-intensity laser field using a
      quantum-mechanical S-matrix theory. We show that quantum interference between the
      contributions of different intermediate excited states of the singly charged
      argon ion produces a transition from back-to-back to side-by-side emission with
      increasing laser intensity, which is in close agreement with the experimental
      data. For higher intensities, this transition is enhanced by the consequences of
      depletion of the excited states. 

PMID- 24579594
TI  - Rare-gas clusters in intense extreme-ultraviolet pulses from a high-order
      harmonic source.
AB  - We report evidence for two previously unidentified effects in the ionization of
      rare-gas clusters by intense extreme-ultraviolet pulses. First, electron spectra
      indicate multistep photoemission with increasing isotropy for larger clusters due
      to electron-atom collisions. Second, very slow (meV) electrons are interpreted as
      the first experimental evidence for Rydberg-like atomic state formation in the
      nanoplasma expansion. Only small fractions of Xe2+ ions were found, in sharp
      contrast to previous results recorded under comparable conditions [Murphy et al.,
      Phys. Rev. Lett. 101, 203401 (2008). 

PMID- 24579596
TI  - Elimination of the A-square problem from cavity QED.
AB  - We generalize the Power-Zineau-Woolley transformation to obtain a canonical
      Hamiltonian of cavity quantum electrodynamics for arbitrary geometry of
      boundaries. This Hamiltonian is free from the A-square term and the instantaneous
      Coulomb interaction between distinct atoms. The single-mode models of cavity QED
      (Dicke, Tavis-Cummings, Jaynes-Cummings) are justified by a term by term mapping
      to the proposed microscopic Hamiltonian. As one straightforward consequence, the
      basis of no-go argumentations concerning the Dicke phase transition with atoms in
      electromagnetic fields dissolves. 

PMID- 24579597
TI  - Quantum up-conversion of squeezed vacuum states from 1550 to 532 nm.
AB  - Squeezed vacuum states constitute a particularly useful resource in quantum
      information as well as in quantum metrology. The frequency conversion of these
      states is important to provide the bridge between different wavelengths within a
      sequence of downstream applications and also to provide a way for squeezed-state
      generation at so-far inaccessible wavelengths. Here we demonstrate the external
      quantum up-conversion of carrier-light-free squeezed vacuum states for the first
      time. Our result proves that nondegenerate sum-frequency generation preserves the
      coherences that are present between photon pairs and higher-order photon pairs of
      the squeezed input state. 

PMID- 24579595
TI  - Novel collective autoionization process observed in electron spectra of He
      clusters.
AB  - The ionization dynamics of He nanodroplets irradiated with intense femtosecond
      extreme ultraviolet pulses of up to 1013  W/cm2 power density have been
      investigated by photoelectron spectroscopy. Helium droplets were resonantly
      excited to atomiclike 2p states with a photon energy of 21.4 eV, below the
      ionization potential (Ip), and directly into the ionization continuum with 42.8
      eV photons. While electron emission following direct ionization above Ip is well
      explained within a model based on a sequence of direct electron emission events,
      the resonant excitation provides evidence of a new, collective ionization
      mechanism involving many excited atomiclike 2p states. With increasing power
      density the direct photoline due to an interatomic Coulombic decay disappears. It
      indicates that ionization occurs due to energy exchange between at least three
      excited atoms proceeding on a femtosecond time scale. In agreement with recent
      theoretical work the novel ionization process is very efficient and it is
      expected to be important for many other systems. 

PMID- 24579598
TI  - Phase stabilization of a frequency comb using multipulse quantum interferometry.
AB  - From the interaction between a frequency comb and an atomic qubit, we derive
      quantum protocols for the determination of the carrier-envelope offset phase,
      using the qubit coherence as a reference, and without the need of frequency
      doubling or an octave spanning comb. Compared with a trivial interference
      protocol, the multipulse protocol results in a polynomial enhancement of the
      sensitivity O(N-2) with the number N of laser pulses involved. We specialize the
      protocols using optical or hyperfine qubits, Lambda schemes, and Raman
      transitions, and introduce methods where the reference is another phase-stable cw
      laser or frequency comb. 

PMID- 24579599
TI  - Single-photon switch based on Rydberg blockade.
AB  - All-optical switching is a technique in which a gate light pulse changes the
      transmission of a target light pulse without the detour via electronic signal
      processing. We take this to the quantum regime, where the incoming gate light
      pulse contains only one photon on average. The gate pulse is stored as a Rydberg
      excitation in an ultracold atomic gas using electromagnetically induced
      transparency. Rydberg blockade suppresses the transmission of the subsequent
      target pulse. Finally, the stored gate photon can be retrieved. A retrieved
      photon heralds successful storage. The corresponding postselected subensemble
      shows an extinction of 0.05. The single-photon switch offers many interesting
      perspectives ranging from quantum communication to quantum information
      processing. 

PMID- 24579600
TI  - Observation of infinite-range intensity correlations above, at, and below the
      mobility edges of the 3D Anderson localization transition.
AB  - We investigate long-range intensity correlations on both sides of the Anderson
      transition of classical waves in a three-dimensional disordered material. Our
      ultrasonic experiments are designed to unambiguously detect a recently predicted
      infinite-range C0 contribution, due to local density of states fluctuations near
      the source. We find that these C0 correlations, in addition to C2 and C3
      contributions, are significantly enhanced near mobility edges. Separate
      measurements of the inverse participation ratio reveal a link between C0 and the
      anomalous dimension Delta2, implying that C0 may also be used to explore the
      critical regime of the Anderson transition. 

PMID- 24579601
TI  - Arbitrary control of electromagnetic flux in inhomogeneous anisotropic media with
      near-zero index.
AB  - We propose a method to control electromagnetic flux in an almost arbitrary way in
      wavelength and subwavelength scales. The capability of subwavelength flux control
      is enabled by the evanescent waves induced in a class of inhomogeneous
      anisotropic media with a near-zero permittivity component. By designing the
      spatial profile of the other permittivity component in such inhomogeneous media,
      the flow and distribution of energy flux can be conveniently manipulated. This
      method provides another approach to efficiently control electromagnetic flux in
      nonmagnetic media. 

PMID- 24579602
TI  - Quantum chaos in an ultrastrongly coupled bosonic junction.
AB  - The semiclassical and quantum dynamics of two ultrastrongly coupled nonlinear
      resonators cannot be explained using the discrete nonlinear Schrodinger equation
      or the Bose-Hubbard model, respectively. Instead, a model beyond the rotating
      wave approximation must be studied. In the semiclassical limit this model is not
      integrable and becomes chaotic for a finite window of parameters. For the quantum
      dimer we find corresponding regions of stability and chaos. The more striking
      consequence for both semiclassical and quantum chaos is that the tunneling time
      between the sites becomes unpredictable. These results, including the transition
      to chaos, can be tested in experiments with superconducting microwave resonators.

PMID- 24579603
TI  - Finite-time and finite-size scaling of the Kuramoto oscillators.
AB  - Phase transition in its strict sense can only be observed in an infinite system,
      for which equilibration takes an infinitely long time at criticality. In
      numerical simulations, we are often limited both by the finiteness of the system
      size and by the finiteness of the observation time scale. We propose that one can
      overcome this barrier by measuring the nonequilibrium temporal relaxation for
      finite systems and by applying the finite-time-finite-size scaling (FTFSS) which
      systematically uses two scaling variables, one temporal and the other spatial.
      The FTFSS method yields a smooth scaling surface, and the conventional finite
      size scaling curves can be viewed as proper cross sections of the surface. The
      validity of our FTFSS method is tested for the synchronization transition of
      Kuramoto models in the globally coupled structure and in the small-world network
      structure. Our FTFSS method is also applied to the Monte Carlo dynamics of the
      globally coupled q-state clock model. 

PMID- 24579604
TI  - Flexible fiber in a turbulent flow: a macroscopic polymer.
AB  - We describe, for the first time, an experiment devoted to the study of the
      spatial conformation of a flexible fiber in a turbulent flow. We propose a model
      for the transition from rigid to flexible regimes as the intensity of turbulence
      is increased or the elastic energy of the fiber is decreased. This transition
      occurs for a fiber typical length which is observed experimentally and recovered
      by our analysis. We also demonstrate that the conformations of flexible fibers in
      a turbulent flow are analog to conformations of flexible polymers in a good
      solvent. This last result opens some new and creative ways to model flexible
      fiber distortions in turbulent flows while addressing fundamental problems in
      polymer dynamics. 

PMID- 24579605
TI  - Hyperchaotic intermittent convection in a magnetized viscous fluid.
AB  - We consider a low-dimensional model of convection in a horizontally magnetized
      layer of a viscous fluid heated from below. We analyze in detail the stability of
      hydrodynamic convection for a wide range of two control parameters. Namely, when
      changing the initially applied temperature difference or magnetic field strength,
      one can see transitions from regular to irregular long-term behavior of the
      system, switching between chaotic, periodic, and equilibrium asymptotic
      solutions. It is worth noting that owing to the induced magnetic field a
      transition to hyperchaotic dynamics is possible for some parameters of the model.
      We also reveal new features of the generalized Lorenz model, including both type
      I and III intermittency. 

PMID- 24579606
TI  - Narrow-band emission in Thomson sources operating in the high-field regime.
AB  - We present a novel and quite general analysis of the interaction of a high-field
      chirped laser pulse and a relativistic electron, in which exquisite control of
      the spectral brilliance of the up-shifted Thomson-scattered photon is shown to be
      possible. Normally, when Thomson scattering occurs at high field strengths, there
      is ponderomotive line broadening in the scattered radiation. This effect makes
      the bandwidth too large for some applications and reduces the spectral
      brilliance. We show that such broadening can be corrected and eliminated by
      suitable frequency modulation of the incident laser pulse. Furthermore, we
      suggest a practical realization of this compensation idea in terms of a chirped
      beam-driven free electron laser oscillator configuration and show that
      significant compensation can occur, even with the imperfect matching to be
      expected in these conditions. 

PMID- 24579607
TI  - Dissociation and the development of spatial correlation in a molecular ultracold
      plasma.
AB  - Penning ionization initiates the evolution of a dense molecular Rydberg gas to
      plasma. This process selects for pairs of excited molecules separated by a
      distance of two Rydberg orbital diameters or less. The deactivated Penning
      partners predissociate, depleting the leading edge of the distribution of nearest
      neighbor distances. For certain density and orbital radii, this sequence of
      events can form a plasma in which large distances separate a disproportionate
      fraction of the ions. Experimental results and model calculations suggest that
      the reduced potential energy of this Penning lattice significantly affects the
      development of strong coupling in an ultracold plasma. 

PMID- 24579608
TI  - Energetic stability of coreless vortices in spin-1 Bose-Einstein condensates with
      conserved magnetization.
AB  - We show that conservation of longitudinal magnetization in a spinor condensate
      provides a stabilizing mechanism for a coreless vortex phase-imprinted on a polar
      condensate. The stable vortex can form a composite topological defect with
      distinct small- and large-distance topology: the inner ferromagnetic coreless
      vortex continuously deforms toward an outer singular, singly quantized polar
      vortex. A similar mechanism can also stabilize a nonsingular nematic texture in
      the polar phase. A weak magnetization is shown to destabilize a coreless vortex
      in the ferromagnetic phase. 

PMID- 24579609
TI  - Observation of a strong atom-dimer attraction in a mass-imbalanced Fermi-Fermi
      mixture.
AB  - We investigate a mixture of ultracold fermionic K40 atoms and weakly bound Li6K40
      dimers on the repulsive side of a heteronuclear atomic Feshbach resonance. By
      radio-frequency spectroscopy we demonstrate that the normally repulsive atom
      dimer interaction is turned into a strong attraction. The phenomenon can be
      understood as a three-body effect in which two heavy K40 fermions exchange the
      light Li6 atom, leading to attraction in odd partial-wave channels (mainly p
      wave). Our observations show that mass imbalance in a fermionic system can
      profoundly change the character of interactions as compared to the well
      established mass-balanced case. 

PMID- 24579610
TI  - Jahn-Teller, polarity, and insulator-to-metal transition in BiMnO3 at high
      pressure.
AB  - The interaction of coexisting structural instabilities in multiferroic materials
      gives rise to intriguing coupling phenomena and extraordinarily rich phase
      diagrams, both in bulk materials and strained thin films. Here we investigate the
      multiferroic BiMnO3 with its peculiar 6s2 electrons and four interacting
      mechanisms: electric polarity, octahedra tilts, magnetism, and cooperative Jahn
      Teller distortion. We have probed structural transitions under high pressure by
      synchrotron x-ray diffraction and Raman spectroscopy up to 60 GPa. We show that
      BiMnO3 displays under pressure a rich sequence of five phases with a great
      variety of structures and properties, including a metallic phase above 53 GPa
      and, between 37 and 53 GPa, a strongly elongated monoclinic phase that allows
      ferroelectricity, which contradicts the traditional expectation that
      ferroelectricity vanishes under pressure. Between 7 and 37 GPa, the Pnma
      structure remains remarkably stable but shows a reduction of the Jahn-Teller
      distortion in a way that differs from the behavior observed in the archetypal
      orthorhombic Jahn-Teller distorted perovskite LaMnO3. 

PMID- 24579611
TI  - Nonlocal first-principles calculations in Cu-Au and other intermetallic alloys.
AB  - Cu-Au is the prototypical alloy system used to exemplify ordering and compound
      formation, and it serves as a testbed for all new alloy theory methods. Yet,
      despite the importance of this system, conventional density functional theory
      (DFT) calculations with semilocal approximations have two dramatic failures in
      describing the energies of this system: (1) DFT formation energies of the
      observed Cu3Au and CuAu compounds are nearly a factor of 2 smaller in magnitude
      than experimental values, and (2) DFT predicts incorrect ordered ground states
      ground states for Au-rich compositions. Here, we show how modern extensions of
      DFT based on nonlocal interactions can rectify both of these failures. Our
      corrections shed light on improving the theoretical predictions for alloy systems
      to determine accurate formation energies, order-disorder critical temperatures,
      phase diagrams, and high-throughput computations. 

PMID- 24579612
TI  - Bimodal island size distribution in heteroepitaxial growth.
AB  - A bimodal size distribution of two-dimensional islands is inferred during
      interface formation in heteroepitaxial growth of bismuth ferrite on (001)
      oriented SrTiO3 by sputter deposition. Features observed by in situ x-ray
      scattering are explained by a model where coalescence of islands determines the
      growth kinetics with negligible surface diffusion on SrTiO3. Small clusters
      maintain a compact shape as they coalesce, while clusters beyond a critical size
      impinge to form large irregular connected islands and a population of smaller
      clusters forms in the spaces between the larger ones. 

PMID- 24579613
TI  - First-principles study of secondary slip in zirconium.
AB  - Although the favored glide planes in hexagonal close-packed Zr are prismatic,
      screw dislocations can escape their habit plane to glide in either pyramidal or
      basal planes. Using ab initio calculations within the nudged elastic band method,
      we show that, surprisingly, both events share the same thermally activated
      process with an unusual conservative motion of the prismatic stacking fault
      perpendicularly to itself. Halfway through the migration, the screw dislocation
      adopts a nonplanar metastable configuration with stacking faults in adjacent
      prismatic planes joined by a two-layer pyramidal twin. 

PMID- 24579614
TI  - Phononic frequency combs through nonlinear resonances.
AB  - We explore an analogue of optical frequency combs in driven nonlinear phononic
      systems, and present a mechanism for generating phononic frequency combs through
      nonlinear resonances. In the underlying process, a set of phonon modes is
      simultaneously excited by the external driving which yields frequency combs with
      an array of discrete and equidistant spectral lines of each nonlinearly excited
      phonon mode. Frequency combs through nonlinear resonance of different orders are
      investigated, and in particular the possibility of correlation tailoring in
      higher-order cases is revealed. We suggest that our results can be applied in
      various nonlinear acoustic processes, such as phonon harvesting, and can also be
      generalized to other nonlinear systems. 

PMID- 24579615
TI  - Emergent collective phenomena in a mixture of hard shapes through active
      rotation.
AB  - We investigate collective phenomena with rotationally driven spinners of concave
      shape. Each spinner experiences a constant internal torque in either a clockwise
      or counterclockwise direction. Although the spinners are modeled as hard,
      otherwise noninteracting rigid bodies, their active motion induces an effective
      interaction that favors rotation in the same direction. With increasing density
      and activity, phase separation occurs via spinodal decomposition, as well as self
      organization into rotating crystals. We observe the emergence of cooperative,
      superdiffusive motion along interfaces, which can transport inactive test
      particles. Our results demonstrate novel phase behavior of actively rotated
      particles that is not possible with linear propulsion or in nondriven,
      equilibrium systems of identical hard particles. 

PMID- 24579616
TI  - Criticality and quenched disorder: Harris criterion versus rare regions.
AB  - We employ scaling arguments and optimal fluctuation theory to establish a general
      relation between quantum Griffiths singularities and the Harris criterion for
      quantum phase transitions in disordered systems. If a clean critical point
      violates the Harris criterion, it is destabilized by weak disorder. At the same
      time, the Griffiths dynamical exponent z' diverges upon approaching the
      transition, suggesting unconventional critical behavior. In contrast, if the
      Harris criterion is fulfilled, power-law Griffiths singularities can coexist with
      clean critical behavior, but z' saturates at a finite value. We present
      applications of our theory to a variety of systems including quantum spin chains,
      classical reaction-diffusion systems and metallic magnets, and we discuss
      modifications for transitions above the upper critical dimension. Based on these
      results we propose a unified classification of phase transitions in disordered
      systems. 

PMID- 24579617
TI  - Water-mediated cooperative migration of chemisorbed hydrogen on graphene.
AB  - The kinetics associated with the migration of chemisorbed hydrogen on a graphene
      sheet is studied using density-functional theory. Chemisorbed H atoms interact
      strongly through the carbon sheet and each chemisorbed H atom must form a pair
      with a H atom bound on the opposite side of the sheet in order to lower the
      energy with respect to the free H2 state. The two H atoms in a pair are
      correlated and migrate cooperatively. Because of the strong C-H bonds, the
      barrier to H cooperative migration is higher than 2.0 eV. However, when mediated
      by H2O molecules, the barrier can be reduced to less than 0.8 eV. The H pairing
      up leads to distinctive behavior of graphene hydrogenation, different from H
      chemisorption on a graphite surface. This study also demonstrates the superior
      effectiveness of water activation of C-H bonds and uncovers the mystery of fast
      kinetics of H spillover [Y. W. Li and R. T. Yang, J. Am. Chem. Soc. 128, 8136
      (2006). 

PMID- 24579618
TI  - Enhanced atomic-scale spin contrast due to spin friction.
AB  - Atom manipulation with the magnetic tip of a scanning tunneling microscope is a
      versatile technique to construct and investigate well-defined atomic spin
      arrangements. Here we explore the possibility of using a magnetic adatom as a
      local probe to image surface spin textures. As a model system we choose a Neel
      state with 120 degrees  between neighboring magnetic moments. Close to the
      threshold of manipulation, the adatom resides in the threefold, magnetically
      frustrated hollow sites, and consequently no magnetic signal is detected in
      manipulation images. At smaller tip-adatom distances, however, the adatom is
      moved towards the magnetically active bridge sites and due to the exchange force
      of the tip the manipulation process becomes spin dependent. In this way the
      adatom can be used as an amplifying probe for the surface spin texture. 

PMID- 24579619
TI  - Room temperature Frenkel-Wannier-Mott hybridization of degenerate excitons in a
      strongly coupled microcavity.
AB  - Hybrid organic-inorganic polaritons are formed by the simultaneous strong
      coupling of two degenerate excitons and a microcavity photon at room temperature.
      Wannier-Mott and Frenkel excitons in spatially separated ZnO and 3,4,7,8
      napthalene tetracarboxylic dianhydride (NTCDA) layers, respectively, placed in a
      single Fabry-Perot microcavity contribute to the interaction with the cavity. A
      Rabi splitting of (322+/-8)  meV between the upper and middle branches of the
      three branch polariton energy-momentum dispersion is observed. This is compared
      to only (224+/-22)  meV and (218+/-8)  meV Rabi splittings for NTCDA-only and ZnO
      only reference cavities, respectively, and indicates that the excitonic component
      of the polariton is a Frenkel-Wannier-Mott hybrid. Unlike previous reports of
      hybrid polaritons, the mixing of the organic and inorganic eigenstates occurs
      independently of angle due to their energetic degeneracy, and can be tailored by
      adjusting the optical field distribution within the cavity. 

PMID- 24579620
TI  - Optomechanics with cavity polaritons: dissipative coupling and unconventional
      bistability.
AB  - We study a hybrid system formed from an optomechanical resonator and a cavity
      mode strongly coupled to an excitonic transition inside a quantum well. We show
      that due to the mixing of cavity photon and exciton states, the emergent
      quasiparticles-polaritons-possess coupling to the mechanical mode of both a
      dispersive and dissipative nature. We calculate the occupancies of polariton
      modes and reveal bistable behavior, which deviates from conventional Kerr
      nonlinearity or dispersive coupling cases due to the dissipative coupling. The
      described system serves as a good candidate for future polaritonic devices. 

PMID- 24579621
TI  - Accurate homogeneous electron gas exchange-correlation free energy for local spin
      density calculations.
AB  - An accurate analytical parametrization for the exchange-correlation free energy
      of the homogeneous electron gas, including interpolation for partial spin
      polarization, is derived via thermodynamic analysis of recent restricted path
      integral Monte Carlo (RPIMC) data. This parametrization constitutes the local
      spin density approximation (LSDA) for the exchange-correlation functional in
      density functional theory. The new finite-temperature LSDA reproduces the RPIMC
      data well, satisfies the correct high-density and low- and high-T asymptotic
      limits, and is well behaved beyond the range of the RPIMC data, suggestive of
      broad utility. 

PMID- 24579622
TI  - Magnetotransport subband spectroscopy in InAs nanowires.
AB  - We report on magnetotransport measurements in InAs nanowires under a large
      magnetic field (up to 55 T), providing a spectroscopy of the one-dimensional
      electronic band structure. Large modulations of the conductance mediated by a
      control of the Fermi energy reveal the Landau fragmentation, carrying the
      fingerprints of the confined InAs material. Our numerical simulations of the
      magnetic band structure consistently support the experimental results and reveal
      key parameters of the electronic confinement. 

PMID- 24579623
TI  - Photoelectron spin-polarization control in the topological insulator Bi2Se3.
AB  - We study the manipulation of the spin polarization of photoemitted electrons in
      Bi2Se3 by spin- and angle-resolved photoemission spectroscopy. General rules are
      established that enable controlling the photoelectron spin-polarization. We
      demonstrate the +/- 100% reversal of a single component of the measured spin
      polarization vector upon the rotation of light polarization, as well as full
      three-dimensional manipulation by varying experimental configuration and photon
      energy. While a material-specific density-functional theory analysis is needed
      for the quantitative description, a minimal yet fully generalized two-atomic
      layer model qualitatively accounts for the spin response based on the interplay
      of optical selection rules, photoelectron interference, and topological surface
      state complex structure. It follows that photoelectron spin-polarization control
      is generically achievable in systems with a layer-dependent, entangled spin
      orbital texture. 

PMID- 24579624
TI  - Hybrid microwave-cavity heat engine.
AB  - We propose and analyze the use of hybrid microwave cavities as quantum heat
      engines. A possible realization consists of two macroscopically separated quantum
      dot conductors coupled capacitively to the fundamental mode of a microwave
      cavity. We demonstrate that an electrical current can be induced in one conductor
      through cavity-mediated processes by heating up the other conductor. The heat
      engine can reach Carnot efficiency with optimal conversion of heat to work. When
      the system delivers the maximum power, the efficiency can be a large fraction of
      the Carnot efficiency. The heat engine functions even with moderate electronic
      relaxation and dephasing in the quantum dots. We provide detailed estimates for
      the electrical current and output power using realistic parameters. 

PMID- 24579625
TI  - Plasmons due to the interplay of Dirac and Schrodinger fermions.
AB  - We study the interplay between Dirac and Schrodinger fermions in the polarization
      properties of a two-dimensional electron gas (2DEG). Specifically, we analyze the
      low-energy sector of narrow-gap semiconductors described by a two-band Kane
      model. In the context of quantum spin Hall insulators, particularly, in Hg(Cd)Te
      quantum wells, this model is named the Bernevig-Hughes-Zhang model.
      Interestingly, it describes electrons with intermediate properties between Dirac
      and Schrodinger fermions. We calculate the dynamical dielectric function of such
      a model at zero temperature within random phase approximation. Surprisingly,
      plasmon resonances are found in the intrinsic (undoped) limit, whereas they are
      absent-in that limit-in graphene as well as ordinary 2DEGs. Additionally, we
      demonstrate that the optical conductivity offers a quantitative way to identify
      the topological phase of Hg(Cd)Te quantum wells from a bulk measurement. 

PMID- 24579626
TI  - Strong coupling of the iron-quadrupole and anion-dipole polarizations in Ba(Fe(1
      x)Co(x))2As2.
AB  - We use a quantitative convergent beam electron diffraction based method to image
      the valence electron density distribution in Ba(Fe1-xCox)2As2. We show a
      remarkable increase in both the charge quadrupole of the Fe cations and the
      charge dipole of the arsenic anions upon Co doping from x=0 (Tc=0  K) to x=0.1
      (Tc=22.5  K). Our data suggest that an unexpected electronic correlation effect,
      namely strong coupling of Fe orbital fluctuation and anion electronic
      polarization, is present in iron-based superconductors. 

PMID- 24579627
TI  - Parity measurement in topological Josephson junctions.
AB  - We study the properties of a topological Josephson junction made of both edges of
      a two-dimensional topological insulator. We show that, due to fermion parity
      pumping across the bulk, the global parity of the junction has a clear signature
      in the periodicity and critical value of the Josephson current. In particular, we
      find that the periodicity with the flux changes from 4pi in a junction with an
      even number of quasiparticles to 2pi in the odd sector. In the case of long
      junctions, we exhibit a rigorous mathematical connection between the spectrum of
      Andreev bound states and the fermion parity anomaly, through bosonization.
      Additionally, we discuss the rather quantitative effects of Coulomb interactions
      on the Josephson current. 

PMID- 24579628
TI  - Manipulation of a two-photon pump in superconductor-semiconductor
      heterostructures.
AB  - We investigate the photon statistics, entanglement, and squeezing of a p-n
      junction sandwiched between two superconducting leads and show that such an
      electrically driven photon pump generates correlated and entangled pairs of
      photons. In particular, we demonstrate that the squeezing of the fluctuations in
      the quadrature amplitudes of the emitted light can be manipulated by changing the
      relative phase of the order parameters of the superconductors. This reveals how
      macroscopic coherence of the superconducting state can be used to tailor the
      properties of a two-photon state. 

PMID- 24579629
TI  - Vortex core reversal due to spin wave interference.
AB  - In this Letter we address spin wave dynamics involved in fast and selective
      vortex core polarity reversal by rotating magnetic field bursts. In a first
      example we explain the origin of the delayed switching for excitations with short
      bursts of only one period duration as an interference effect between spin wave
      modes. Second, when the vortex core is initially no longer at rest but in
      gyrotropic motion, the magnetization dynamics become more complicated and the
      interaction of spin waves with the vortex core leads to a variety of nonlinear
      effects. Our analysis allows us to explain the experimentally observed switching
      diagram for simultaneous excitation of spin waves and gyrotropic mode. 

PMID- 24579630
TI  - Ferromagnetism and Borromean binding in three-fermion clusters.
AB  - A three-particle spin-12 fermion problem with on-site repulsion and nearest
      neighbor attraction is solved on the two-dimensional square lattice by
      discretizing a Schrodinger equation in momentum space. Energies of bound
      complexes (trions) and their binding conditions are obtained. For total spin
      S=1/2, a wide region of trion instability toward decaying into a stable singlet
      pair plus a free fermion is identified. The instability is attributed to the
      formation of a wave function node upon addition of the third fermion. In the
      S=3/2 sector, trions are found to form in the absence of bound pairs indicating
      Borromean binding. In the strong coupling limit the system transitions from an
      S=1/2 ground state to a ferromagnetic S=3/2 ground state in agreement with the
      Nagaoka theorem for a four-site plaquette. 

PMID- 24579631
TI  - Calculation of multipolar exchange interactions in spin-orbital coupled systems.
AB  - A new method of computing multipolar exchange interaction in spin-orbit coupled
      systems is developed using multipolar tensor expansion of the density matrix in
      local density approximation+U electronic structure calculation. Within the mean
      field approximation, exchange constants can be mapped into a series of total
      energy calculations by the pair-flip approximation technique. The application to
      uranium dioxide shows an antiferromagnetic superexchange coupling in dipoles but
      a ferromagnetic one in quadrupoles which is very different from past studies.
      Further calculation of the spin-lattice interaction indicates it is of the same
      order with the superexchange and characterizes the overall behavior of the
      quadrupolar part as a competition between them. 

PMID- 24579632
TI  - Generic spin model for the honeycomb iridates beyond the Kitaev limit.
AB  - Recently, realizations of Kitaev physics have been sought in the A2IrO3 family of
      honeycomb iridates, originating from oxygen-mediated exchange through edge-shared
      octahedra. However, for the jeff=1/2 Mott insulator in these materials, exchange
      from direct d-orbital overlap is relevant, and it was proposed that a Heisenberg
      term should be added to the Kitaev model. Here, we provide the generic nearest
      neighbor spin Hamiltonian when both oxygen-mediated and direct overlap are
      present, containing a bond-dependent off-diagonal exchange in addition to
      Heisenberg and Kitaev terms. We analyze this complete model using a combination
      of classical techniques and exact diagonalization. Near the Kitaev limit, we find
      new magnetic phases, 120 degrees  and incommensurate spiral order, as well as
      extended regions of zigzag and stripy order. Possible applications to Na2IrO3 and
      Li2IrO3 are discussed. 

PMID- 24579633
TI  - Role of antiferromagnetic ordering in the (1*2) surface reconstruction of Ca(Fe(1
      x)Co(x))2As2.
AB  - Low energy electron diffraction, scanning tunneling microscopy and spectroscopy,
      and first-principles spin-dependent density functional theory are utilized to
      investigate the geometric, electronic, and magnetic structures of the stripe
      ordered (1*2) surface of Ca(Fe1-xCox)2As2 (x=0, 0.075). The surface is terminated
      with a 50% Ca layer. Compared to the bulk, the surface Ca layer has a large
      inward relaxation (~0.5  A), and the underneath As-Fe2-As layer displays a
      significant buckling. First-principles calculations show that the (1*2) phase is
      stabilized by the bulk antiferromagnetic spin ordering through the spin-charge
      lattice coupling. Strikingly, a superconducting gap (~7  meV at 7.4 K) is
      observed to spatially coexist with the (1*2) phase (x=0.075 compound). This
      implies the coexistence of both superconductivity and AFM ordering at the
      surface. 

PMID- 24579634
TI  - Direct determination of exchange parameters in Cs2CuBr4 and Cs2CuCl4: high-field
      electron-spin-resonance studies.
AB  - Spin-1/2 Heisenberg antiferromagnets Cs2CuCl4 and Cs2CuBr4 with distorted
      triangular-lattice structures are studied by means of electron spin resonance
      spectroscopy in magnetic fields up to the saturation field and above. In the
      magnetically saturated phase, quantum fluctuations are fully suppressed, and the
      spin dynamics is defined by ordinary magnons. This allows us to accurately
      describe the magnetic excitation spectra in both materials and, using the
      harmonic spin-wave theory, to determine their exchange parameters. The viability
      of the proposed method was proven by applying it to Cs2CuCl4, yielding
      J/kB=4.7(2)  K, J'/kB=1.42(7)  K, [J'/J?0.30] and revealing good agreement with
      inelastic neutron-scattering results. For the isostructural Cs2CuBr4, we obtain
      J/kB=14.9(7)  K, J'/kB=6.1(3)  K, [J'/J?0.41], providing exact and conclusive
      information on the exchange couplings in this frustrated spin system. 

PMID- 24579635
TI  - Extraordinary absorption of decorated undoped graphene.
AB  - We theoretically study absorption by an undoped graphene layer decorated with
      arrays of small particles. We discuss periodic and random arrays within a common
      formalism, which predicts a maximum absorption of 50% for suspended graphene in
      both cases. The limits of weak and strong scatterers are investigated, and an
      unusual dependence on particle-graphene separation is found and explained in
      terms of the effective number of contributing evanescent diffraction orders of
      the array. Our results can be important to boost absorption by single-layer
      graphene due to its simple setup with potential applications to light harvesting
      and photodetection based on energy (Forster) rather than charge transfer. 

PMID- 24579637
TI  - Internal structure of inertial granular flows.
AB  - We analyze inertial granular flows and show that, for all values of the inertial
      number I, the effective friction coefficient MU arises from three different
      parameters pertaining to the contact network and force transmission: (1) contact
      anisotropy, (2) force chain anisotropy, and (3) friction mobilization. Our
      extensive 3D numerical simulations reveal that MU increases with I mainly due to
      an increasing contact anisotropy and partially by friction mobilization whereas
      the anisotropy of force chains declines as a result of the destabilizing effect
      of particle inertia. The contact network undergoes topological transitions, and
      beyond I?0.1 the force chains break into clusters immersed in a background "soup"
      of floating particles. We show that this transition coincides with the divergence
      of the size of fluidized zones characterized from the local environments of
      floating particles and a slower increase of MU with I. 

PMID- 24579636
TI  - Long-lived heteronuclear spin-singlet states in liquids at a zero magnetic field.
AB  - We report an observation of long-lived spin-singlet states in a 13C-1H spin pair
      in a zero magnetic field. In 13C-labeled formic acid, we observe spin-singlet
      lifetimes as long as 37 s, about a factor of 3 longer than the T1 lifetime of
      dipole polarization in the triplet state. In contrast to common high-field
      experiments, the observed coherence is a singlet-triplet coherence with a
      lifetime T2 longer than the T1 lifetime of dipole polarization in the triplet
      manifold. Moreover, we demonstrate that heteronuclear singlet states formed
      between a 1H and a 13C nucleus can exhibit longer lifetimes than the respective
      triplet states even in the presence of additional spins that couple to the spin
      pair of interest. Although long-lived homonuclear spin-singlet states have been
      extensively studied, this is the first experimental observation of analogous
      singlet states in heteronuclear spin pairs.

PMID- 24579638
TI  - Reversible state transition in nanoconfined aqueous solutions.
AB  - Using molecular dynamics simulations, we find a reversible transition between the
      dispersion and aggregation states of solute molecules in aqueous solutions
      confined in nanoscale geometry, which is not observed in macroscopic systems. The
      nanoscale confinement also leads to a significant increase of the critical
      aggregation concentration (CAC). A theoretical model based on Gibbs free energy
      calculation is developed to describe the simulation results. It indicates that
      the reversible state transition is attributed to the low free energy barrier (of
      order kBT) in between two energy minima corresponding to the dispersion and
      aggregation states, and the enhancement of the CAC results from the fact that at
      lower concentrations the number of solute molecules is not large enough to allow
      the formation of a stable cluster in the confined systems. 

PMID- 24579639
TI  - Predicted rupture force of a single molecular bond becomes rate independent at
      ultralow loading rates.
AB  - We present for the first time a theoretical model of studying the saturation of
      the rupture force of a single molecular bond that causes the rupture force to be
      rate independent under an ultralow loading rate. This saturation will obviously
      bring challenges to understanding the rupture behavior of the molecular bond
      using conventional methods. This intriguing feature implies that the molecular
      bond has a nonzero strength at a vanishing loading rate. We find that the
      saturation behavior is caused by bond rebinding when the loading rate is lower
      than a limiting value depending on the loading stiffness. 

PMID- 24579640
TI  - Interplay between Turing mechanisms can increase pattern diversity.
AB  - We use the context of dryland vegetation to study a general problem of complex
      pattern-forming systems: multiple pattern-forming instabilities that are driven
      by distinct mechanisms but share the same spectral properties. We find that the
      co-occurrence of two Turing instabilities when the driving mechanisms counteract
      each other in some region of the parameter space results in the growth of a
      single mode rather than two interacting modes. The interplay between the two
      mechanisms compensates for the simpler dynamics of a single mode by inducing a
      wider variety of patterns, which implies higher biodiversity in dryland
      ecosystems. 

PMID- 24579641
TI  - Multiscale atmospheric dynamics: cross-frequency phase-amplitude coupling in the
      air temperature.
AB  - Interactions between dynamics on different temporal scales of about a century
      long record of data of the daily mean surface air temperature from various
      European locations have been detected using a form of the conditional mutual
      information, statistically tested using the Fourier-transform and multifractal
      surrogate data methods. An information transfer from larger to smaller time
      scales has been observed as the influence of the phase of slow oscillatory
      phenomena with the periods around 6-11 yr on the amplitudes of the variability
      characterized by the smaller temporal scales from a few months to 4-5 yr. The
      overall effect of the slow oscillations on the interannual temperature
      variability within the range 1-2  degrees  C has been observed in large areas of
      Europe. 

PMID- 24579642
TI  - Comment on "Ear deformations give bats a physical mechanism for fast adaptation
      of ultrasonic beam patterns".

PMID- 24579643
TI  - Compressed sensing MRI: a review.
AB  - Compressed sensing (CS) is a mathematical framework that reconstructs data from
      highly undersampled measurements. To gain acceleration in acquisition time, CS
      has been applied to MRI and has been demonstrated on diverse MRI methods. This
      review discusses the important requirements to qualify MRI to become an optimal
      application of CS, namely, sparsity, pseudo-random undersampling, and nonlinear
      reconstruction. By utilizing concepts of transform sparsity and compression, CS
      allows acquisition of only the important coefficients of the signal during the
      acquisition. A priori knowledge of MR images specifically related to transform
      sparsity is required for the application of CS. In this paper, Section I
      introduces the fundamentals of CS and the idea of CS as applied to MRI. The
      requirements for application of CS to MRI is discussed in Section II, while the
      various acquisition techniques, reconstruction techniques, the advantages of
      combining CS and parallel imaging, and sampling mask design problems are
      discussed in Section III. Numerous applications of CS in MRI due to its ability
      to improve imaging speed are reviewed in section IV. Clinical evaluations of some
      of the CS applications recently published are discussed in Section V. Section VI
      provides information on available open source software that could be used for CS
      implementations. 

PMID- 24579645
TI  - Vibration arthrometry: a critical review.
AB  - The clinical value of sounds and vibrations produced by biological joints in
      motion has been studied extensively since 1902, aimed at developing a technology
      to aid the interpretation of recorded joint vibration signals. Such technology
      would have clear advantages to current medical imaging systems, e.g. MRI, in
      speed, cost, and non-invasiveness. However, it has yet to achieve routine
      clinical use. This review aims to provide a balanced analysis of past and present
      attempts to progress vibration arthrometry. The literature reveals significant
      barriers to successful implementation of vibration arthrometry. From a technical
      standpoint, accounting for the intense variability within recorded signals caused
      by shifting characteristics of contacting joint surfaces and forces during motion
      is the primary issue. Additionally, understandable scepticism in the clinical
      community as to the reliability of vibration arthrometry represents a significant
      barrier to adoption. In conclusion, until the variability issue is shown to be
      adequately dealt with, and clear transparent evidence of clinical usefulness to
      orthopedic medicine demonstrated, it will be difficult to move the field forward.
      Future work should lead toward proving value to clinicians, and be transparent
      about how the variability issue has been resolved. 

PMID- 24579646
TI  - From the gait laboratory to the rehabilitation clinic: translation of motion
      analysis and modeling data to interventions that impact anterior cruciate
      ligament loads in gait and drop landing.
AB  - In female athletes the risk of anterior cruciate ligament (ACL) injury during
      impact-related activities such as landing is higher compared to males. Both how
      and why this occurs has been at the forefront of orthopedic sports medicine
      research over the past 20 years. Many individuals with an ACL-deficient knee
      compensate for joint instability in an effort to remain physically active. Yet
      others do not compensate and are faced with a reduction in their activities
      and/or meniscus tears and eventually osteoarthritis. In this article we attempt
      to link 2 distinct but related scientific disciplines (in vivo motion analysis
      assessment and computational modeling) to show how these techniques have emerged
      as powerful tools in our understanding of knee function. Normal knee function and
      the biomechanics of the ACL-deficient (ACLd) and ACL-reconstructed (ACLr) knee
      are summarized. Basic experiments concerning the mechanism of noncontact ACL
      injury as well as performance adaptations in ACLd and ACLr knees are reviewed,
      and the biomechanics of the normal, ACLd, and ACLr knees under more strenuous
      activities, such as landing from a jump, are provided. 

PMID- 24579647
TI  - Simulation of the upper urinary system.
AB  - The ureter and its peristalsis motions have long been of significant interest in
      biomechanics. In this article we review experimental, theoretical, and numerical
      studies of the behavior of the ureter together with its mechanical properties,
      emphasizing studies that contain information of importance in building a virtual
      simulation tool of the complete ureter that includes its complex geometry,
      nonlinear material properties, and interaction with urine flow. A new technique
      to model the contraction of a ureter, which directly applies wall forces to model
      pacemaker activities, is presented. The required further steps to capture the
      full complex movement of the peristalsis are discussed, aiming to construct a
      computational platform that will provide a reliable tool to assist in the
      investigation and design of material devices (stents) for the renal system. 

PMID- 24579644
TI  - Metabolomic fingerprinting: challenges and opportunities.
AB  - Systems biology has primarily focused on studying genomics, transcriptomics, and
      proteomics and their dynamic interactions. These, however, represent only the
      potential for a biological outcome since the ultimate phenotype at the level of
      the eventually produced metabolites is not taken into consideration. The emerging
      field of metabolomics provides complementary guidance toward an integrated
      approach to this problem: It allows global profiling of the metabolites of a
      cell, tissue, or host and presents information on the actual end points of a
      response. A wide range of data collection methods are currently used and allow
      the extraction of global or tissue-specific metabolic profiles. The great amount
      and complexity of data that are collected require multivariate analysis
      techniques, but the increasing amount of work in this field has made easy-to-use
      analysis programs readily available. Metabolomics has already shown great
      potential in drug toxicity studies, disease modeling, and diagnostics and may be
      integrated with genomic and proteomic data in the future to provide in-depth
      understanding of systems, pathways, and their functionally dynamic interactions.
      In this review we discuss the current state of the art of metabolomics, its
      applications, and future potential. 

PMID- 24579648
TI  - Brain-computer interfaces for neurorehabilitation.
AB  - Brain-computer interfaces (BCIs) enable control of computers and other assistive
      devices, such as neuro-prostheses, which are used for communication, movement
      restoration, neuro-modulation, and muscle stimulation, by using only signals
      measured directly from the brain. A BCI creates a new output channel for the
      brain to a computer or a device. This requires retrieval of signals of interest
      from the brain, and its use for neuro-rehabilitation by means of interfacing the
      signals to a computerized device. Brain signals such as action potentials from
      single neurons or nerve fibers, extracellular local field potentials (LFPs),
      electrocorticograms, electroencephalogram and its components such as the event
      related brain potentials, real-time functional magnetic resonance imaging, near
      infrared spectroscopy, and magneto-encephalogram have been used. BCIs are
      envisaged to be useful for communication, control and self-regulation of brain
      function. BCIs employ neurofeedback to enable operant conditioning to allow the
      user to learn using it. Paralytic conditions arising from stroke or other
      diseases are being targeted for BCI application. Neurofeedback strategies ranging
      from sensory feedback to direct brain stimulation are being employed. Existing
      BCIs are limited in their throughput in terms of letters per minute or commands
      per minute, and need extensive training to use the BCI. Further, they can cause
      rapid fatigue due to use and have limited adaptability to changes in the
      patient's brain state. The challenge before BCI technology for neuro
      rehabilitation today is to enable effective clinical use of BCIs with minimal
      effort to set up and operate. 

PMID- 24579650
TI  - Coping strategies in individuals after traumatic brain injury: associations with
      health-related quality of life.
AB  - PURPOSE: This study investigates coping strategies after traumatic brain injury
      (TBI) and their associations with health-related quality of life (HRQoL).
      METHODS: Participants were 141 adults followed up 3 months to 15 years after TBI
      of all severity degrees. Coping was assessed by the Freiburg Questionnaire of
      Coping with Illness (FQCI) and HRQoL by the Quality of Life after Brain Injury
      (QOLIBRI) scale and the Short Form-36 Health Survey (SF-36). Coping dimensions
      were extracted by principal component analysis. Multiple linear regression
      analysis was used to identify predictors of coping strategies. RESULTS: Two
      factors for coping after TBI were extracted: Action/Distraction and
      Trivialisation/Resignation. The Trivialisation/Resignation strategy was
      negatively correlated with all aspects of HRQoL, while relationships with the
      Action/Distraction strategy were positive and significant for two domains. These
      two factors also showed significant associations with anxiety, depression,
      recovery, cognitive status, mood states and trauma severity. Multiple regression
      analysis identified recovery status as a predictor for the maladaptive
      Trivialisation/Resignation strategy. CONCLUSION: Two coping factors were
      identified, which were differentially associated with HRQoL. Maladaptive coping
      strategies play a particularly important role, and less reliance on such
      strategies is associated with better HRQoL; use of adaptive strategies should
      correspondingly be fostered. IMPLICATIONS FOR REHABILITATION: This study
      highlights the relationship of coping strategies and HRQoL after TBI. For the
      assessment of HRQoL a novel disease-specific instrument was applied, that
      provides in detail TBI-relevant aspects of well-being and HRQoL. Individuals
      after TBI use two main sets of coping strategies that are differentially
      associated with HRQoL (and clinical variables). One is adaptive and the other
      maladaptive for HRQoL after TBI. Maladaptive and adaptive coping strategies used
      by the individual should be identified and considered in rehabilitation efforts
      to improve HRQoL after TBI.

PMID- 24579649
TI  - Walking activity of children with cerebral palsy and children developing
      typically: a comparison between the Netherlands and the United States.
AB  - PURPOSE: To compare walking activity of children with and without cerebral palsy
      (CP) between the Netherlands and the United States. METHODS: A cross-sectional
      analysis on walking activity data from an international retrospective comparison
      study including a convenience sample of 134 walking children aged 7-12 years with
      spastic CP, classified as Gross Motor Function Classification System (GMFCS)
      level I (N = 64), II (N = 49) or III (N = 21), and 223 typically developing
      children (TDC) from the Netherlands and the United States. Walking activity was
      assessed during a one-week period using a StepWatchTM activity monitor. Outcomes
      were the daily number of strides, daily time being inactive and spent at low (0
      15 strides/min), moderate (16-30 strides/min) and high stride rate (31-60
      strides/min). Walking activity was compared between countries using multiple
      linear regression analyses. RESULTS: Walking activity of TDC was not
      significantly different between countries. Compared to their American
      counterparts, Dutch children in GMFCS level I and II showed less walking activity
      (p < 0.05), whereas Dutch children in GMFCS level III showed more walking
      activity (p < 0.05). CONCLUSION: The absence of differences in walking activity
      between Dutch and American TDC, and the presence of differences in walking
      activity between Dutch and American children with CP suggest that between-country
      differences affect walking activity differently in children with CP. IMPLICATIONS
      FOR REHABILITATION: Physical activity of children with CP should be promoted in
      both the United States and the Netherlands. The between-country differences in
      walking activity illustrate that apart from the severity of the CP walking
      activity seems to be influenced by environmental aspects. In the promotion of
      physical activity, practitioners should pay attention to environmental barriers
      that families may experience for increasing physical activity.

PMID- 24579651
TI  - The applicability of four clinical methods to evaluate arm and hand function in
      all stages of spinal muscular atrophy type II.
AB  - AIM: To evaluate the ability of four clinical methods to reflect arm and hand
      function at impairment and activity level and to determine their ability to
      discriminate among SMA II patients of all ages and in all stages of the disease.
      METHODS: Fifty-two patients with SMA II (age range: 8-73 years) were assessed by
      means of the Egen Klassifikation 2 (EK2 scale), the Motor Function Measure Scale
      (MFM D3), the Manual Muscle Test (MMT) and Hand-Held Dynamometry (HHD) in full
      fist grip and lateral pinch grip. Patients were classified into six levels of
      upper limb function by means of the Brooke Upper Limb Scale, and the four
      methods' ability to differentiate among patients within these levels was
      calculated. Modified versions of the EK2 scale (EK Upper Limb) and the MFM D3
      (MFM D3 Upper Limb) were assessed in the same manner. RESULTS: The patients'
      physical abilities were best described by the MMT and EK2 while the "EK Upper
      Limb", MFM D3 and MMT were best at discriminating among patients across the range
      of upper limb function. Quantitative muscle tests as measured by CitecTM HHD were
      less applicable to weak patients; full fist grip could discriminate among
      patients at Brooke levels 3-5, and lateral pinch grip among the strongest
      patients. CONCLUSION: At the impairment level, MMT is the superior measure of
      muscle function in very weak patients in whom HHD cannot reflect capacity. At the
      activity level, the EK 2 represents daily activities whereas the MFM D3 measures
      motor functions. In differentiating among SMA II patients of all ages and in all
      stages of the disease, the ability of abbreviated versions of scales targeting
      upper limb function is superior to unabridged versions of these scales.
      IMPLICATIONS FOR REHABILITATION: Evaluation of upper limb function in spinal
      muscular atrophy II Even very weak patients with SMA II have some residual upper
      limb function that is measurable if the right method is chosen. The Manual muscle
      test is applicable to all patients with SMA II and is useful to determine
      possible interventions - such as methods to drive a wheelchair or operate a
      computer. Abbreviated versions of the EK2 scale and the MFM are useful as methods
      to evaluate subtle changes in upper limb function resulting from disease
      progression or interventions.

PMID- 24579653
TI  - Competition between sp3-C-N vs sp3-C-F reductive elimination from Pd(IV)
      complexes.
AB  - This communication describes the design of a model system that allows direct
      investigation of competing sp(3)-C-N and sp(3)-C-F bond-forming reductive
      elimination from a Pd(IV) fluoro sulfonamide complex. The reductive elimination
      selectivity varies dramatically as a function of reaction additives. A mechanism
      is proposed that provides a rationale for these effects. 

PMID- 24579654
TI  - How do we identify RHD variants using a practical molecular approach?
AB  - Serologic resolution of Rh discrepancies due to partial D or weak D phenotypes is
      a frequent problem encountered during routine typing that can be solved by RHD
      genotyping because it provides better characterization of these variants. The
      objective of the current study was to develop algorithms for identification of D
      variants in multiethnic populations based on a logic sequence of molecular tests
      using a large number of atypical RhD specimens. Thus, a total of 360 blood
      samples with atypical D antigen expression were analyzed. A previously published
      multiplex polymerase chain reaction (PCR) procedure was performed and depending
      on multiplex PCR analysis, the associated RHCE allele, and D variant frequency in
      our population, an algorithm was developed composed of six flow charts using
      specific PCR-restriction fragment length polymorphism and/or specific exon
      sequencing. This strategy allowed the identification of 22 different variants
      with few assays and a much reduced cost. This study describes a simple and
      practical algorithm that we use to determine RHD genotypes in samples with
      unknown RHD. This strategy is relatively easy to implement and the algorithm can
      be adapted to populations with various ethnic backgrounds after an initial
      assessment of the type and frequency of D variants. Essentially, we demonstrate
      that sequencing of all RHD exons is not necessary for the identification of the
      majority of known D variants. 

PMID- 24579652
TI  - Strabismus genetics across a spectrum of eye misalignment disorders.
AB  - Eye misalignment, called strabismus, is amongst the most common phenotypes
      observed, occurring in up to 5% of individuals in a studied population. While
      misalignment is frequently observed in rare complex syndromes, the majority of
      strabismus cases are non-syndromic. Over the past decade, genes and pathways
      associated with syndromic forms of strabismus have emerged, but the genes
      contributing to non-syndromic strabismus remain elusive. Genetic testing for
      strabismus risk may allow for earlier diagnosis and treatment, as well as
      decreased frequency of surgery. We review human and model organism literature
      describing non-syndromic strabismus, including family, twin, linkage, and gene
      expression studies. Recent advances in the genetics of Duane retraction syndrome
      are considered, as relatives of those impacted show elevated familial rates of
      non-syndromic strabismus. As whole genome sequencing efforts are advancing for
      the discovery of the elusive strabismus genes, this overview is intended to
      support the interpretation of the new findings. 

PMID- 24579655
TI  - When right differs from left: human limb directional asymmetry emerges during
      very early development.
AB  - The often observed directional asymmetry (DA) in human limb bones may have a
      genetic/developmental basis and/or could emerge from different mechanical
      loadings across sides due to handedness. Because behavioural lateralization in
      itself has a genetic basis, it has been suggested that DA in limbs could develop
      prenatally as a pre-adaptation to adult life. However, the presence of consistent
      differences in the size of left and right limb bones in early development is
      understudied. We study asymmetry in limb bones during early development (10-20
      weeks of gestation) in a sample of 178 aborted foetuses. Statistically
      significant DA was found in several upper and lower limb bones, where the right
      hand side was consistently larger than the left. We argue that this pattern is
      probably the consequence of developmental processes related to internal
      asymmetric positioning of organs. 

PMID- 24579656
TI  - Activity of disinfectants against multispecies biofilms formed by Staphylococcus
      aureus, Candida albicans and Pseudomonas aeruginosa.
AB  - Microbial biofilms are a serious threat to human health. Recent studies have
      indicated that many clinically relevant biofilms are polymicrobial. In the
      present study, multispecies biofilms were grown in a reproducible manner in a 96
      well microtiter plate. The efficacy of nine commercially available disinfectants
      against Staphylococcus aureus, Candida albicans, and Pseudomonas aeruginosa in
      multispecies biofilms was determined and compared. The results showed that the
      direction and the magnitude of the effect in a multispecies biofilm depend on the
      strain and the disinfectant used and challenge the common belief that organisms
      in multispecies biofilms are always less susceptible than in monospecies
      biofilms. 

PMID- 24579657
TI  - Determination of oxidative stress and cellular inflammation in patients with
      diabetic nephropathy and non-diabetic nephropathy being administered hemodialysis
      treatment due to chronic renal failure.
AB  - OBJECTIVES: We aimed to evaluate oxidative stress [8-hydroxydeoxyguanosine (8
      OHdG), malondialdehyde (MDA)] endothelial damage [asymmetric dimethylarginine
      (ADMA)] and markers of cellular inflammation [interleukin 6 (IL-6), tumor
      necrosis factor-alpha (TNF-alpha), neopterin (NP) and high-sensitivity C-reactive
      protein (hsCRP)] in patients with diabetic nephropathy (DN) and non-diabetic
      nephropathy who were being administered hemodialysis treatment because of chronic
      renal failure. METHODS: In determining 8-OHdG, IL-6 and TNF-alpha levels, Enzyme
      Linked Immuno-Sorbent Assay method was used. Serum MDA, ADMA and NP levels were
      determined by using high performance liquid chromatography (HPLC). And hs-CRP
      values were measured with nephelometric method. RESULTS: Serum 8-OHdG and MDA
      levels were found statistically to have increased when compared with those of the
      control group in patients groups after dialysis. However, serum ADMA and
      neopterin levels were observed statistically to have decreased when compared with
      those of the control group in patients groups after dialysis. But, decreases on
      ADMA and neopterin levels are still much higher than those of control. IL-6 and
      TNF-alpha levels were found to have increased when compared with those of control
      group in patients groups before dialysis. CONCLUSION: The oxidative stress in
      patients with DN, who were being treated with hemodialysis due to chronic renal
      failure, was higher than that of non-DN patients who were being treated with
      hemodialysis. In contrast with this, inflammation occurring in non-DN patients
      was found to have been higher than that of in patients with DN.

PMID- 24579658
TI  - Periapical lesions are not always a sequelae of pulpal necrosis: a retrospective
      study of 1521 biopsies.
AB  - AIM: To record the incidence of lesions that were not the sequelae of pulpal
      necrosis (non-SPN) amongst 1521 biopsies of periapical lesions submitted with a
      clinical diagnosis of a sequelae of pulpal necrosis (SPN). METHODOLOGY: A
      retrospective study of 1521 biopsy request forms of specimens submitted for
      histopathological examination with a clinical diagnosis 'periapical
      inflammation', 'periapical abscess', 'periapical granuloma' or 'periapical cyst'
      during an arbitrarily selected 14-year period was undertaken. Gender and age of
      the patient, site and maximum diameter of the lesion, symptoms, inclusion of the
      final diagnosis in the differential diagnosis and specialty of the clinician
      submitting the biopsy material were recorded in each case. The final diagnosis
      for each case was extracted from the pathology report, and two groups were
      formed, SPN and non-SPN lesions. Differences between the respective features of
      SPN and non-SPN cases were analysed with Yate's chi-square test and t-test
      (significance level P < 0.05) RESULTS: In 52 of the 1521 cases examined (3.42%),
      the histological diagnosis was not consistent with a SPN. In most non-SPN cases,
      the histopathological diagnosis was not included in the differential diagnosis.
      The keratocystic odontogenic tumour [odontogenic keratocyst (OKC)] was the most
      frequent non-SPN lesion (34.62%). Other, yet less frequent, non-SPN lesions
      included glandular odontogenic cysts, lateral periodontal cysts, central
      ossifying fibromas as well as malignancies (metastatic carcinomas and Langerhans
      cell histiocytosis). CONCLUSIONS: Non-SPN lesions appeared in the periapical
      region mimicking a SPN, although rarely. Most of them were developmental cysts,
      in particular OKCs, but odontogenic tumours, such as ameloblastoma, or malignant
      lesions were also diagnosed. Histological examination of tissue harvested from
      periapical lesions should be performed, in particular when those lesions are
      large.

PMID- 24579660
TI  - Predictors of functional recovery in adults with posterior fossa ependymomas.
AB  - OBJECT: After complete resection and radiation therapy, the 10-year overall
      survival rates for adult patients with posterior fossa ependymomas approach 85%.
      This favorable outcome profile emphasizes the critical importance of functional
      preservation to this patient population. Here, the authors identify predictors of
      functional outcome following microsurgical resection of adult posterior fossa
      ependymomas. METHODS: The authors identified adult patients with newly diagnosed
      WHO Grade II posterior fossa ependymomas who underwent microsurgical resection at
      the Barrow Neurological Institute from 1990 to 2011. Clinical and radiographic
      variables were collected, including volumetric extent of resection, foramen of
      Luschka extension, cystic changes, peritumoral T2 signal changes, Karnofsky
      Performance Scale (KPS) score, National Institutes of Health Stroke Scale (NIHSS)
      score, progression-free survival (PFS), and overall survival (OS). RESULTS: Forty
      five patients were identified, with a median clinical follow-up of 103 months.
      The median PFS and OS were 6.8 and 8.6 years, respectively. Extent of resection
      and adjuvant radiotherapy were predictive of improved PFS (p = 0.005) and were
      nonsignificantly associated with improved OS. Univariate analysis revealed that
      tumor size (p < 0.001), cystic changes (p < 0.01), postoperative T2 signal (p <
      0.01), and CSF diversion (p = 0.048) predicted functional and neurological
      recovery rates, based on KPS and NIHSS scores, respectively. Multivariate
      regression analysis identified tumor size (p < 0.001), cystic changes (p = 0.01),
      and CSF diversion (p = 0.02) as independent predictors of slower functional
      recovery, while only tumor size (p = 0.007) was an independent predictor of
      neurological recovery. Specifically, by 6 weeks postoperatively, baseline KPS
      score was recovered by only 43.8% of patients with tumors larger than 30 cm(3)
      (vs 72.4% patients with tumors < 30 cm(3)), 35.3% of patients with cystic tumors
      (vs 78.6% of patients with noncystic tumors), and 46.7% of patients requiring CSF
      diversion (vs 70% of patients not requiring CSF diversion). CONCLUSIONS: Greater
      extent of resection and adjuvant radiotherapy significantly improve PFS in adult
      patients with posterior fossa ependymomas. Tumor size, cystic changes, and the
      need for CSF diversion were independent predictors of the rate of functional
      recovery in this patient population. Taken together, these functional outcome
      predictors may guide preoperative estimations of recovery following microsurgical
      resection.

PMID- 24579659
TI  - Enhanced removal of methylene blue and methyl violet dyes from aqueous solution
      using a nanocomposite of hydrolyzed polyacrylamide grafted xanthan gum and
      incorporated nanosilica.
AB  - The synthesis and characterization of a novel nanocomposite is reported that was
      developed as an efficient adsorbent for the removal of toxic methylene blue (MB)
      and methyl violet (MV) from aqueous solution. The nanocomposite comprises
      hydrolyzed polyacrylamide grafted onto xanthan gum as well as incorporated
      nanosilica. The synthesis exploits the saponification of the grafted
      polyacrylamide and the in situ formation of nanoscale SiO2 by a sol-gel reaction,
      in which the biopolymer matrix promotes the silica polymerization and therefore
      acts as a novel template for nanosilica formation. The detailed investigation of
      the kinetics and the adsorption isotherms of MB and MV from aqueous solution
      showed that the dyes adsorb rapidly, in accordance with a pseudo-second-order
      kinetics and a Langmuir adsorption isotherm. The entropy driven process was
      furthermore found to strongly depend on the point of zero charge (pzc) of the
      adsorbent. The remarkably high adsorption capacity of dyes on the nanocomposites
      (efficiency of MB removal, 99.4%; maximum specific removal Qmax, 497.5 mg g(-1);
      and efficiency of MV removal, 99.1%; Qmax, 378.8 mg g(-1)) is rationalized on the
      basis of H-bonding interactions as well as dipole-dipole and electrostatic
      interactions between anionic adsorbent and cationic dye molecules. Because of the
      excellent regeneration capacity the nanocomposites are considered interesting
      materials for the uptake of, for instance, toxic dyes from wastewater. 

PMID- 24579661
TI  - Assessment of intracranial dynamics in hydrocephalus.

PMID- 24579663
TI  - Glioblastoma in elderly patients.

PMID- 24579664
TI  - Searching for a global oral health policy for gerodontology.

PMID- 24579662
TI  - Prospective natural history study of central nervous system hemangioblastomas in
      von Hippel-Lindau disease.
AB  - OBJECT: The tumors most frequently associated with von Hippel-Lindau (VHL)
      disease are hemangioblastomas. While they are associated with significant
      neurological impairment and mortality, their natural history and optimal
      management have not been fully defined. METHODS: Patients with VHL were enrolled
      in a prospective study designed to define the natural history of CNS
      hemangioblastomas. In the present analysis, serial imaging, laboratory, genetic,
      and clinical data were evaluated in those with at least 2 years of follow-up
      data. RESULTS: At study entrance 225 patients (111 males, 114 females) harbored
      1921 CNS hemangioblastomas in the supratentorial compartment (21 tumors [1%]),
      cerebellum (865 [45%]), brainstem (129 [7%]), spinal cord (689 [36%]), cauda
      equina (212 [11%]), and nerve roots (5 [0.3%]; follow-up 15,819 hemangioblastoma
      years). Increased tumor burden was associated with partial deletions in the VHL
      gene (p = 0.005) and male sex (p = 0.002). Hemangioblastoma development (median
      0.3 new tumors/year) was associated with younger age (p < 0.0001) and more tumors
      at study entrance (p < 0.0001). While 1278 hemangioblastomas (51%) did not grow,
      1227 hemangioblastomas (49%) grew in a saltatory (886 [72%]), linear (76 [6%]),
      or exponential (264 [22%]) pattern. Faster tumor growth was associated with male
      sex (p = 0.001), symptomatic tumors (p < 0.0001), and tumors associated with
      cysts (p < 0.0001). Location-dependent tumor size was the primary predictor of
      eventual symptom formation (159 symptomatic tumors [6.3%]; area under the curve >
      0.9). CONCLUSIONS: Central nervous system hemangioblastoma burden in VHL is
      associated with partial germline deletions and male sex. Unpredictable growth of
      hemangioblastomas compromises assessment of nonsurgical therapies. The judicious
      treatment of symptom-producing hemangioblastomas, while avoiding unnecessary
      treatment of asymptomatic tumors that may not progress, can provide clinical
      stability.

PMID- 24579666
TI  - Suspension culture of pluripotent stem cells: effect of shear on stem cell fate.
AB  - Despite significant promise, the routine usage of suspension cell culture to
      manufacture stem cell-derived differentiated cells has progressed slowly.
      Suspension culture is an innovative way of either expanding or differentiating
      cells and sometimes both are combined into a single bioprocess. Its advantages
      over static 2D culturing include a homogeneous and controllable culture
      environment and producing a large quantity of cells in a fraction of time. This
      feature makes suspension cell culture ideal for use in stem cell research and
      eventually ideal in the large-scale production of differentiated cells for
      regenerative medicine. Because of their tremendous differentiation capacities and
      unlimited growth properties, pluripotent stem cells (PSCs) in particular are
      considered potential sources for future cell-replacement therapies. Currently,
      expansion of PSCs is accomplished in 2D, which only permits a limited amount of
      cell growth per culture flask before cells need to be passaged. However, before
      stem cells can be applied clinically, several aspects of their expansion, such as
      directed growth, but also differentiation, need to be better controlled. This
      review will summarize recent advantages in suspension culture of PSCs, while at
      the same time highlighting current challenges. 

PMID- 24579665
TI  - Quantitative proteomics in laser capture microdissected sleep nuclei from rat
      brain.
AB  - The combination of stable isotope labeling of amino acids in mammals (SILAM) and
      laser capture microdissection (LCM) for selective proteomic analysis of the
      targeted tissues holds tremendous potential for refined characterization of
      proteome changes within complex tissues such as the brain. The authors have
      applied this approach to measure changes in relative protein abundance in ventral
      tegmental area (VTA) of the rat brain that correlate to pharmacological
      perturbations. Enriched (13)C6(15)N2-lysine was introduced in vivo via diet.
      These animals were sacrificed during the middle of the 12-hour light period to
      extract isotopically "heavy" proteins, which were then used as a reference for
      extracts from dosed, unlabeled rats. Animals were administered an orexin peptide
      (Ox-B), an orexin receptor antagonist (ORA), or a mixture of both (Ox-B + ORA).
      All samples were obtained at same phase of the sleep cycle. Labeled-pair
      identification and differential quantitation provided protein identification and
      expression ratio data. Five proteins were found to exhibit decreased relative
      abundance after administration of an ORA, including alpha-synuclein and rat
      myelin basic protein. Conversely, six proteins showed increased relative
      abundance upon antagonist treatment, including 2',3'-cyclic nucleotide 3'
      phosphodiesterase.

PMID- 24579668
TI  - The different molecular mechanisms of mitophagy between yeast and mammals.
AB  - The mitochondrion is the site of energy metabolism inside the cell; which
      produces ATP for vital activities. The accumulation of damaged mitochondria
      affects cell survival, these organelles are removed via mitophagy to maintain
      cell vitality. Currently, mitophagy is a hot topic in life science research.
      Understanding the role of mitophagy in pathogenesis and its association with the
      genesis of disease is important for developing treatments for many human
      diseases. Here, we summarize current progress in the study of mitophagy and
      describe the different molecular mechanisms of mitophagy between yeast and
      mammals, as well as related diseases. 

PMID- 24579667
TI  - Review of poly (ADP-ribose) polymerase (PARP) mechanisms of action and rationale
      for targeting in cancer and other diseases.
AB  - Poly (ADP-ribose) polymerases (PARPs) are a family of related enzymes that share
      the ability to catalyze the transfer of ADP-ribose to target proteins. PARPs play
      an important role in various cellular processes, including modulation of
      chromatin structure, transcription, replication, recombination, and DNA repair.
      The role of PARP proteins in DNA repair is of particular interest, in view of the
      finding that certain tumors defective in homologous recombination mechanisms, may
      rely on PARP-mediated DNA repair for survival, and are sensitive to its
      inhibition. PARP inhibitors may also increase tumor sensitivity to DNA-damaging
      agents. Clinical trials of PARP inhibitors are investigating the utility of these
      approaches in cancer. The hyperactivation of PARP has also been shown to result
      in a specific programmed cell death pathway involving NAD+/ATP depletion, mu
      calpain activation, loss of mitochondrial membrane potential, and the release of
      apoptosis inducing factor. Hyperactivation of the PARP pathway may be exploited
      to selectively kill cancer cells. Other PARP forms, including tankyrase 1 (PARP
      5a), which plays an important role in enhancing telomere elongation by
      telomerase, have been found to be potential targets in cancer therapy. The PARP
      pathway and its inhibition thus offers a number of opportunities for therapeutic
      intervention in both cancer and other disease states. 

PMID- 24579669
TI  - MicroRNAs in gastric cancer metastasis.
AB  - Gastric cancer (GC) is common worldwide and has a high rate of metastasis. The
      underlying molecular mechanism of metastasis are not entirely clear. MicroRNAs
      (miRNAs) are small, non-coding RNA molecules that regulate gene expression post
      transcriptionally and are reported to be involved in multiple steps of tumor
      metastasis. Clarifying their roles in GC metastasis will improve understanding of
      this disease. Here, we review the involvement of miRNAs in multiple steps of GC
      metastasis, including epithelial-mesenchymal transitions, anoikis, angiogenesis,
      invasion, and migration. The clinical application of miRNAs as prognostic
      biomarkers in GC is also discussed. 

PMID- 24579670
TI  - MicroRNAs in bladder cancer: expression profiles, biological functions,
      regulation, and clinical implications.
AB  - Bladder cancer (UBC) is a common cancer worldwide and has a high rate of
      recurrence and progression despite systemic therapy. The molecular mechanisms of
      UBC are not completely understood. MicroRNAs are noncoding RNA molecules of
      approximately 23 nucleotides that play important roles in multiple steps during
      the progression of UBC. Here, we review the expression profiles of miRNAs and
      their biological functions, regulation, and clinical implications in UBC. Either
      down-regulation or up-regulation of miRNAs occurs in UBC through epigenetic
      changes or defects of the biogenesis apparatus. Deregulation of miRNAs is
      involved in cell-cycle arrest, apoptosis, proliferation, metastasis, drug
      resistance, and other functions in UBC. A number of miRNAs, including urine
      miRNAs, have been associated with tumor type, stage, or patient survival, and
      miRNAs might be developed as diagnostic or prognostic markers. Better
      understanding of the roles of miRNAs in UBC will shed light on the molecular
      mechanisms of UBC. 

PMID- 24579671
TI  - The roles of bacterial GCN5-related N-acetyltransferases.
AB  - The GCN5-related N-acetyltransferase (GNAT) superfamily of proteins, widespread
      in eukaryotes and prokaryotes, can utilize acyl coenzyme A (acyl CoA) to acylate
      respective acceptor substrates and release both CoA and the acylated products.
      GNATs have been shown to be involved in multiple physiological events, including
      bacterial drug resistance, regulation of transcription, stress reaction, and
      metabolic flux, etc. In the last few years, the importance of GNATs has only
      emerged in eukaryotes, but bacterial GNATs, particularly those of pathogens, have
      only recently been explored. In this review, we summarize the main members,
      structures, inhibitors, and activators of proteins in the GNAT family. We focus
      on the roles of GNATs in bacteria, particularly Mycobacterium tuberculosis GNATs.

PMID- 24579672
TI  - 'Should I stay or should I go?' Bacterial attachment vs biofilm formation on
      surface-modified membranes.
AB  - A number of techniques are used for testing the anti-biofouling activity of
      surfaces, yet the correlation between different results is often questionable. In
      this report, the correlation between initial bacterial deposition (fast tests,
      reported previously) and biofilm growth (much slower tests) was analyzed on a
      pristine and a surface-modified reverse osmosis membrane ESPA-1. The membrane was
      modified with grafted hydrophilic polymers bearing negatively charged, positively
      charged and zwitter-ionic moieties. Using three different bacterial strains it
      was found that there was no general correlation between the initial bacterial
      deposition rates and biofilm growth on surfaces, the reasons being different for
      each modified surface. For the negatively charged surface the slowest deposition
      due to the charge repulsion was eventually succeeded by the largest biofilm
      growth, probably due to secretion of extracellular polymeric substances (EPS)
      that mediated a strong attachment. For the positively charged surface, short-term
      charge attraction by quaternary amine groups led to the fastest deposition, but
      could be eventually overridden by their antimicrobial activity, resulting in non
      consistent results where in some cases a lower biofilm formation rate was
      observed. The results indicate that initial deposition rates have to be used and
      interpreted with great care, when used for assessing the anti-biofouling activity
      of surfaces. However, for a weakly interacting 'low-fouling' zwitter-ionic
      surface, the positive correlation between initial cell deposition and biofilm
      growth, especially under flow, suggests that for this type of coating initial
      deposition tests may be fairly indicative of anti-biofouling potential. 

PMID- 24579674
TI  - Mnemonic benefits of retrieval practice at short retention intervals.
AB  - The testing effect refers to the retention benefit conferred by prior retrieval
      of information from memory. Although the testing effect is a robust phenomenon, a
      common assumption is that reliable memory benefits only emerge after long
      retention intervals of days or weeks. The present study focused on potential test
      induced retention benefits for brief retention intervals on the order of minutes
      and tens of seconds. Participants in four experiments studied lists of words.
      Some of the items were subjected to an initial cued recall test, and others were
      re-presented for additional study. Free recall tests were administered in each
      experiment following retention intervals ranging from 30 s to 8 min. When initial
      retrieval practice was successful (Experiments 1 through 3), or feedback
      compensated for unsuccessful retrieval (Experiment 4), significant testing
      effects emerged at all retention intervals. Results are discussed in the context
      of a bifurcated item-distribution model and highlight the importance of initial
      test performance and the type of analysis employed when examining testing effect
      data. 

PMID- 24579675
TI  - Chemoenzymatic total syntheses of ribisins A, B, and D, polyoxygenated benzofuran
      derivatives displaying NGF-potentiating properties.
AB  - Total syntheses of the structures, 1, 2, and 4, assigned to the biologically
      active natural products ribisins A, B, and D, respectively, have been achieved
      using the microbially derived and enantiomerically pure cis-1,2-dihydrocatechol 5
      as starting material. Key steps include Suzuki-Miyaura cross-coupling,
      intramolecular Mitsunobu, and tandem epoxidation/rearrangement reactions. As a
      result of these studies, the structures of ribisins A and D have been confirmed
      while that of congener B was shown to be represented by 31 rather than 2. 

PMID- 24579676
TI  - Preparing people and organizations for the challenge of change.

PMID- 24579678
TI  - Assessing the toxic effects of hydroalcoholic extract of Stachys lavandulifolia
      Vahl on rat's liver.
AB  - AIMS: Stachys lavandulifolia Vahl is a frequently used plant to treat different
      diseases, but its probable toxic effects have not been reported yet. This study
      aimed to study the toxicity of the extract on rats' liver. METHODS: In this
      experimental study, 100 rats were designated into 10 groups and injected normal
      saline or Stachys lavandulifolia Vahl extract at 50, 100, 150, and 200 mg/kg,
      intraperitoneally for 28 days. Four case groups and one control group were
      examined for ALT, AST and ALP after one month and the other groups were evaluated
      after two months. RESULTS: In the first month, the increase of ALP at all doses
      and the increase of AST at 200 mg/kg was significant, compared to the control
      group (p<0.05). In the second month, AST increased at the dosage of 150 mg/kg,
      and ALP decreased at the dosage of 100 mg/kg, compared to the control group
      (p<0.05). Histopathological assessment showed a significant dose dependent
      increase both in necrotic-inflammatory reactions and fibrotic lesions, in the
      first and second months, compared to the control group (p<0.001). CONCLUSIONS:
      The Stachys lavandulifolia extract injected intraperitoneally has hepatotoxic
      effect, which is not eliminated by the drug withdrawal. Therefore, it is
      necessary to be consumed with caution (Tab. 4, Fig. 1, Ref. 21).

PMID- 24579673
TI  - Enhanced tumor delivery of gemcitabine via PEG-DSPE/TPGS mixed micelles.
AB  - Gemcitabine is a potent anticancer drug approved for the treatment of pancreatic,
      non-small-cell lung, breast, and ovarian cancers. The major deficiencies of
      current gemcitabine therapy, however, are its rapid metabolic inactivation and
      narrow therapeutic window. Herein, we employed polyethylene glycol-b
      distearoylphosphatidylethanolamine (PEG-DSPE)/tocopheryl polyethylene glycol 1000
      succinate (TPGS) mixed micelles as a delivery system, to improve the
      pharmacokinetic characteristics of gemcitabine and enhance its antitumor
      efficacy. By conjugating stearic acid to gemcitabine and subsequently
      encapsulating stearoyl gemcitabine (GemC18) within PEG-DSPE/TPGS mixed micelles,
      the deamination of gemcitabine was delayed in vitro and in vivo. Importantly,
      compared to free gemcitabine, GemC18-loaded micelles pronouncedly prolonged the
      circulation time of gemcitabine and elevated its concentration in the tumor by 3
      fold, resulting in superior antitumor efficacy in mice bearing human pancreatic
      cancer BxPC-3 xenografts. Our findings demonstrate the promise of PEG-DSPE/TPGS
      mixed micelles as a nanocarrier system for the delivery of gemcitabine to achieve
      safer and more efficacious therapeutic outcomes. 

PMID- 24579679
TI  - The effect of carnitine on liver regeneration after partial hepatectomy.
AB  - AIM: The role of carnitine in liver regeneration. Can carnitine given externally
      increase and/or fasten the beginning of liver regeneration? RESULTS: Wistar
      Albino rats were used. Group 1: The group, which was applied parenteral carnitine
      after partial hepatectomy and sacrificed on the 1st day. Group 2: The group,
      which was applied parenteral carnitine after partial hepatectomy and sacrificed
      on the 7th day. Group 3: The group, which wasn't applied parenteral carnitine
      after partial hepatectomy and sacrificed in the 1st day. Group 4: The group which
      wasn't applied parenteral carnitne after partial hepatectomy and sacrificed on
      the 7th day. To all the rats, partial liver resection with the rate of 70 % was
      applied. Being started shortly after the resection, 100 mg/kg/day parenteral L
      carnitine was applied to the first and second group. On the 1st and 7th days
      after the resection, eight subjects from each group were sacrificed. To evaluate
      the liver regeneration Ki-67 monoclonal antibody was used. After the examinations
      carried out by pathological clinic, detected mitosis number were examined. The
      1st and 7th day mitosis number of the rats taken into the study was seen as
      statistically significantly higher than the mitosis number of the rats in the
      control group. CONCLUSIONS: As a result, among the rats, which were applied
      hepatectomy, if met by the major conditions triggering liver regeneration
      following the external carnitine supplementation, we can say with the help of the
      information provided by the study measuring the regeneration capacity by
      analysing Ki-67 proliferation index, that external carnitine support can increase
      the capacity of regeneration if it is given in appropriate dose (Tab. 6, Fig. 7,
      Ref. 17).

PMID- 24579680
TI  - The effect of zoledronic acid on growth plates and high turnover bones.
AB  - OBJECTIVES: Bisphosphonates have preventive effect on bone resorption caused by
      osteoclasts.We aimed to investigate the histopathological effects of zoledronic
      acid (ZA) on the jaw and long bones and growth plates of rats. METHODS: Thirty
      six 12 week-old female Sprague-Dawley rats were divided into the control (C,
      n=18) and ZA groups (Z, n=18). Z group animals were administered 0.1 mg/kg saline
      diluted ZA intraperitoneally three times per week for 8 weeks. C group animals
      were administered the same amount of saline simultaneously. At the end of 11th
      week, half the subjects from either the control group (C1) and ZA group (Z1) were
      sacrificed. At the end of 14th week, the remaining half from both groups were
      also sacrificed (C2 and Z2). In all animals, no dental procedures were performed;
      the posterior and anterior mandible and the knee joint including distal femur and
      proximal tibia were histopathologically investigated. RESULTS: Histological
      examination revealed that inflammation and necrosis were limited to the posterior
      mandible of the Z1 and Z2 groups, while the anterior mandible and knee joint
      including distal femur and proximal tibia remained unaffected however the
      development of the growth plate of the proximal tibia was found to be arrested in
      animals of the Z1 and Z2groups. CONCLUSION: Due to it is inhibitory effect over
      growth plate and inflammatory and necrotic effect over high turnover bones,
      zoledronic acid should be administered cautiously, especially in pediatric
      patients who are still in their growth and development stages (Fig. 6, Ref. 34).

PMID- 24579681
TI  - Transplantation of the allogeneic conjunctiva and conjunctival extracellular
      matrix.
AB  - OBJECTIVES: To investigate the characteristics and effects of allogenic
      conjunctiva and conjunctival extracellular matrix (ECM) as the substitute of
      conjunctival tissues. BACKGROUND: The symptoms of the frequently-occurring
      conjunctival injury not only make people ugly, but also lead to blindness, which
      seriously endanger the quality of life of the patients. METHODS: The bulbar
      conjunctivas of 6 out of 30 rabbits were prepared into a conjunctival defect
      model, and the remaining rabbits were randomly divided into 2 groups (n = 12).
      The conjunctivas of the trial group were repaired by transplanting conjunctival
      ECM prepared by tissue engineering technology, and the control group received
      fresh conjunctival allograft. Thereafter, the postoperative conjunctival
      reconstruction was observed. Their conjunctivas were examined by naked eye,
      microscope, immunohistochemical and lymphocyte toxicity tests. RESULTS: Blood
      vessels of the trial group began to grow into the graft after one week, and the
      conjunctivas appeared almost normal without immune rejection after 8 weeks. The
      transplanted conjunctival epitheliums were observed to recover after 4 weeks
      under light microscope. A large number of invasive inflammatory cells were found
      in the grafts of the control group 2 weeks after surgery. CONCLUSION:
      Conjunctival ECM is an ideal substitute for conjunctiva, which can be used for
      the effective surface reconstruction of cornea and conjunctiva (Fig. 7, Ref. 21).

PMID- 24579682
TI  - Longitudinal evaluation of markers of hemostasis in pregnancy.
AB  - OBJECTIVE: The aim of this study was to establish the physiologic changes in
      hemostasis during pregnancy and to find the association between the factor V
      Leiden mutation and adverse pregnancy outcome. METHODS: We investigated blood
      samples of 148 pregnant women during each trimester of pregnancy. We measured
      their serum concentrations of factors I, II, V, VII, VIII, IX, X, XI, XII, D
      dimers, prothrombin time, INR, aPTT, activity of protein C and S, antithrombin
      III and platelet count. The pregnancy outcome of women with factor V Leiden
      mutation was compared to those without congenital thrombophilia. RESULTS:
      Prothrombin time, INR and aPTT were significantly shorter. We found significantly
      higher plasma concentrations of fibrinogen and d-dimers and higher levels of
      activity of factor VII and X in the third trimester. No significant difference
      was found in protein C and antithrombin III activity. The protein S activity was
      lower in the second trimester and it increased in the third trimester. Although
      most of the clotting factors were rising during the pregnancy, there was no
      evidence of fibrinolytic overactivation. In our study, the carriership of factor
      V Leiden mutation did not affect the incidence of preeclampsia, eclampsia,
      intrauterine fetal death and venous thromboembolism. Placental abruption was
      rare. CONCLUSION: Hemostatic changes in pregnancy are significant and essential,
      and have the potential to cause adverse pregnancy outcome. In addition,
      hypercoagulable state during pregnancy is considered to be physiological (Tab. 4,
      Ref. 36).

PMID- 24579683
TI  - Incidence of antibodies in women after failure of assisted reproduction.
AB  - OBJECTIVES: The aim of this study is to determine to what degree antisperm allo
      antibodies (ASA), anti-ovarian antibodies (AOA), anti-zona pellucida antibodies
      (AZPA) and seven anti-phospholipid antibodies (APLA) can explain the failure of
      assisted reproduction technology (ART) in women. BACKGROUND: Among the causes of
      reproductive failure are allo- and autoimmune reactions of the organism against
      reproductive tissues and cells. METHODS: We examined a sample of 43 selected
      women aged 27 to 45 after failure of assisted reproduction technology (ART) via
      intrauterine insemination (IUI), in vitro fertilization (IVF) or intracytoplasmic
      sperm injection (ICSI). Sera from these women were tested by ELISA (enzyme-linked
      immunosorbent assay) (total Ig) for the presence of anti-sperm allo-antibodies
      (ASA), anti-ovarian antibodies (AOA), anti-zona pellucida antibodies (AZPA) and
      seven anti-phospholipid antibodies (APLA). RESULTS: We found 22 (51 %) patients
      positive for the examined antibodies. Among patients with positive results were 3
      miscarriages, 3 biochemical pregnancies (? hCG) and 16 with no evidence of
      conception. Positive APLA was found in 17 patients. Selected immunological
      parameters were negative in 21 (49 %) patients, which means that the tested allo-
      and auto-antibodies did not cause the failure of ART. CONCLUSION: This
      demonstrates that the range of diagnostic tests limits the success of diagnosis
      and the method of dealing with infertile couples. The use of cardiolipin as a
      screening test appears to be insufficient, because in our sample it would have
      caused a 35 % error rate. Investigation of antibodies against seven phospholipids
      is thus considered to be reasonable and is beneficial for infertility diagnosis
      (Tab. 2, Ref. 36).

PMID- 24579684
TI  - Duodenal mucosa in children with coeliac disease in catamnesis and varying
      compliance with the gluten-free diet.
AB  - OBJECTIVES: the aim of the study was to identify the characteristic morphometric
      data changes in the small intestine mucosa in response to varied compliance with
      gluten-free diet in children with coeliac disease. METHODS: 71 children (47 girls
      and 24 boys) aged 2.5 to 16.5 (median age=10.6) with coeliac disease diagnosed
      according to the previously revised ESPGHAN criteria were included in the study.
      The patients were divided into three groups: 1 - on strict GFD, 2 - on semistrict
      GFD, 3 - not on GFD. Quantitative morphometric data on biopsies of duodenal
      mucosa in each group were compared with each other. RESULTS: As compared with
      group 1, patients from group 2 had a lower villous height (Vh)/crypt depth (Cd)
      ratio, but a higher Cd, total cell density of lamina propria, plasma cells
      density in the villi and fibroblasts density in the space between the crypts. In
      patients from group 3, as compared with group 1, we found a significant reduction
      in Vh and Vh/Cd ratio, and a significant decrease in the number of goblet cells.
      At the same time they yielded an increase in Cd, number of intraepithelial
      lymphocytes (IEL), total cell density and plasma cells density throughout the
      lamina propria depth, number of macrophages and neutrophils in the villous lamina
      propria, and number of fibroblasts in the space between crypts. The differences
      were statistically significant. CONCLUSION: Quantitative morphometric parameters
      of small intestine mucosa allow revealing statistically significant differences
      between the groups of children with coeliac disease in response to varied
      compliance with GFD. This enables us to assess the dynamics of the pathological
      process and enhance our understanding of its nature, which is very important for
      improving the therapy and prognosis (Ref. 40).

PMID- 24579685
TI  - The role of laparoscopic Heller myotomy in the treatment of achalasia.
AB  - AIM: To evaluate the results of laparoscopic Heller myotomy in our group of
      patients. METHOD: A retrospective clinical trial was carried out to evaluate the
      indication, technique and controversies of laparoscopic Heller myotomy in the
      achalasia treatment. The following symptoms were evaluated prior and after Heller
      myotomy: dysphagia, heartburn, nausea/vomiting after meal and asthma/coughing.
      The patients were evaluated by the use of Likert score. Statistical analysis was
      performed by using Student t test. The intra-operative (operation time,
      intraoperative complications, blood loss, conversion rate), and peri-operative
      parameters (morbidity, mortality, hospital stay) were evaluated as well. The
      patients who underwent laparoscopic Heller myotomy were included in the trial.
      All patients were perioperatively managed by a multidisciplinary team. RESULTS:
      The evaluation of fourteen patients was performed (average age: 53.2 yrs., eleven
      men, two women, BMI 23.6 kg/m(2)). The patients were indicated for surgery in all
      of the stages (I-III). Previous semiconservative therapeutic modalities were
      performed in thirteen patients. The standard laparoscopic technique for Heller
      myotomy with semifundoplication was applied. All the observed symptoms were
      statistically improved after the surgery (p=0.05). The average operating time was
      89 minutes. Intraoperative blood loss was below 20 ml. There was no conversion to
      open surgery. An average hospital stay was 4.3 days. Morbidity was 14.3 % and
      mortality 0 %. In one patient esophageal mucosa perforation was intra-operatively
      identified and sutured. Post-operative course in this patient was without any
      complications. CONCLUSION: The laparoscopic Heller myotomy has become the "gold
      standard" procedure for achalasia. It is an excellent method allowing precise
      operation technique with good visualization of the esophagogastric junction. The
      operation with this approach is safe, efficient, and with excellent reproducible
      operative results. The correct and early indication for surgery is crucial. The
      delayed diagnosis with a late indication for surgery is not an exemption (Tab. 2,
      Fig. 2, Ref. 36).

PMID- 24579686
TI  - Clinical accuracy of the distinction between Alzheimer's disease and
      frontotemporal lobar degeneration.
AB  - Alzheimer's disease (AD) is the most common cause of dementia. Frontotemporal
      lobar degeneration (FTLD), although less prevalent overall, is almost as common
      as AD in patients under the age of 65. AD and FTLD are histopathologically
      distinct, with AD being characterised by extracellular amyloid plaques and
      intraneuronal neurofibrillary tangles, and FTLD by the presence of non-AD
      histological pathology, most commonly either tau-positive inclusions or ubiquitin
      positive or TDP 43 positive inclusions. Clinically, AD and FTLD may occur with
      overlapping symptoms, especially in the early stages of the disease. In the case
      of Alzheimer's disease, it is represented by isolated decline of recent episodic
      memory; later on, by the impairment of time and space orientation, whereby the
      alteration of social behaviour and amnesic aphasia occur predominantly in the
      advanced phases of the disease. Frontotemporal lobar degeneration is demonstrated
      in three clinical subunits: 1) The behavioural-dysexecutive variant of FTLD
      (frontotemporal dementia, the frontal variant of FTLD, {fvFTLD}), 2) Progressive
      non-fluent aphasia, 3) Semantic dementia (SD) with the profound impairment of
      social conduct (fvFTLD) or with severe speech impairment (PNFA, SD). Considering
      the different clinical symptomatology with FTLD diagnostics, it is necessary to
      use different psychometric tests than in the case of Alzheimer's disease. Therapy
      and the degree of dependence of the affected person are also different. All three
      diseases within the FTLD category, mainly the behavioural-dysexecutive variant,
      require a higher level of nursing care on the part of other persons or
      institutions in comparison with Alzheimer's disease. The goal of our publication
      is to point to the differences in clinical manifestation and the findings of
      auxiliary examinations that are helpful in the clinical accuracy of the
      distinction between these two types of dementia (Tab. 1, Fig. 3, Ref. 18).

PMID- 24579687
TI  - The importance of interictal electroencephalography in paroxysmal states.
AB  - INTRODUCTION: Electroencephalography (EEG) is a non-invasive investigation method
      playing an important role in differential diagnostics of seizures. In this
      article authors point out to its importance, but also limitations. MATERIAL AND
      METHODS: Native interictal EEG findings were evaluated in inpatients after
      solitary unprovoked epileptic seizures (n=84), patients with sporadic epileptic
      seizures (n=179), patients with "chronic" epilepsy (n=324), outpatients with
      epilepsy (n=300), patients with syncope (n=100), patients with neurocardiogenic
      syncope (n=70), patients with migraine (n=100) and patients with tetanic syndrome
      (n=100). EEG findings were evaluated as normal or abnormal and abnormal findings
      were further divided into epileptic and non-epileptic, focal and generalized.
      RESULTS: In native EEG, epileptic manifestations were registered in 14.29 % of
      patients after solitary unprovoked epileptic seizures, in 25.7 % of patients with
      sporadic epileptic seizures, in 37.34 % of patients with chronic epilepsy and in
      32 % of outpatients with epilepsy. Interictal EEG abnormalities (epileptiform and
      non-epileptiform) in non-epileptic diagnoses were at least registered in patients
      with syncope, but also in this group abnormal findings occurred in 30 % of them.
      We registered epileptiform abnormalities in 5 % of patients with migraine, in 4 %
      of patients with tetanic syndrome and in 2 % of patients with syncope.
      CONCLUSION: The diagnosis of epilepsy and non-epileptic seizures is a only a
      clinical diagnosis. EEG is a very important investigational method in this group
      of patients, but still only additional (Tab. 4, Fig. 2, Ref. 14).

PMID- 24579688
TI  - Positive correlation of serum parathormone and prostate specific antigen levels
      in prostate cancer.
AB  - OBJECTIVES: Clinical and experimental observations reveal the exact role of
      vitamin D in prostate cancer. Yet, a complete understanding of the issue
      necessitates the evaluation of the exquisite mechanisms that involve full actors
      of the calcium homeostasis in relation. BACKGROUND: Besides the role of vitamin
      D, parathyroid hormone (PTH) is now understood to be a mitogen for prostate
      cancer cells, and calcium has already been known for such role. The interplay
      between renin-angiotensin-aldosterone system effector hormones and calcium
      homeostasis attracts attention in recent studies. METHODS: Twenty five patients
      with prostate cancer (median age 66 (62-67) years) who had presented at the
      Urology Outpatient Clinic were prospectively included in the study. Also, 30
      volunteer controls (median age 63 (60-70) years) were enrolled for comparison.
      Serum total PSA, intact PTH, calcium, aldosterone and 25-hydroxy vitamin D levels
      were detected in a selected group of patients with prostate cancer. RESULTS: The
      vitamin D levels were lower in PCa patients in line with some of the previous
      studies, supporting the role of vitamin D in prostate cancer. We also observed a
      positive correlation between PTH and PSA both in PCa patients and the controls.
      CONCLUSION: Our findings indicate that like age and race, PSA is associated with
      PTH. The role of PTH, as a master of calcium homeostasis, seems to be neglected
      in prostate carcinogenesis, concerning a very few number of studies pertaining to
      the subject in the literature (Tab. 2, Fig. 2, Ref. 19).

PMID- 24579689
TI  - Hypocalcemia - the most common complication after total thyroidectomy.
AB  - OBJECTIVA: Postoperative intact parathyroid hormone (iPTH) levels and some other
      factors as a predictor of hypocalcemia are analyzed in 115 patients after TTE.
      BACKGROUND: Postoperative hypocalcemia is the most common complication observed
      after total thyroidectomy (TTE). It is not easy to predict in which patients this
      complication will occur. We adopted and implemented a novel method to predict
      this complication - monitoring of postoperative intact parathyroid hormone (iPTH)
      levels. METHODS AND RESULTS: Prospective study involves 115 patients. From
      January till December 2010 we performed 111 TTE and 4 completion thyreoidectomies
      (hemithyreoidectomy (HTE) after previous HTE). Gender and age of patients, final
      histopatology diagnosis, number of parathyroid glands visible during operation,
      duration of operation and surgeon were factors that did not influence development
      of postoperative hypocalcemia. A hospital stay was prolonged in patients with
      hypocalcemia. iPTH level morning after surgery less than 15 pg/ml was a
      statistically significant predictor of postoperative hypocalcemia. Sensitivity,
      specificity, positive and negative predictive value of iPTH<15 pg/ml for
      predicting postoperative hypocalcemia were 71 %, 99 %, 97 % and 86 %,
      respectively. Sensitivity of iPTH<15 pg/ml in predicting symptomatic
      postoperative hypocalcemia was 100 %. CONCLUSION: Measuring iPTH levels morning
      after TTE allows prediction of subsequent hypocalcemia with a high sensitivity,
      specificity, PPV and NPV. Normal iPTH levels ruled out development of
      hypocalcemia symptoms. Patients with normal iPTH can be safely discharged and the
      overtreatment of postthyroidectomy patients with calcium and/or vitamin D
      supplements can be also avoided (Tab. 2, Fig. 3, Ref. 29).

PMID- 24579690
TI  - Hydroarylation of arynes catalyzed by silver for biaryl synthesis.
AB  - A new biaryl synthesis via silver-catalyzed hydroarylation of arynes from acyclic
      building blocks with unactivated arenes in intra- and intermolecular manners has
      been developed. The previously observed Diels-Alder reactions of arynes with
      arene were not observed under the current silver-catalyzed conditions. Deuterium
      scrambling and DFT calculations suggest a stepwise electrophilic aromatic
      substitution mechanism through the formation of a Wheland-type intermediate
      followed by a water-catalyzed proton transfer in the final step of the
      hydroarylation. 

PMID- 24579691
TI  - The beginning of personalized medicine in sepsis: small steps to a bright future.
AB  - There is a growing recognition that there is a need for a more personalized
      approach towards sepsis care. In most clinical trials investigating novel
      therapeutic interventions against sepsis, patients have been considered a rather
      homogeneous population. However, there is probably more individual variability
      between septic patients than previously considered. The pathophysiology of sepsis
      is a complex and dynamic process that originates from the host immune response to
      infection and varies according to the genetic predisposition, immune status and
      co-morbid conditions of the host, the type of pathogen and the site and extent of
      infection. Until now, efforts to stratify septic patients according to their
      immune profile were hampered by the lack of specific biomarkers. Recent advances
      in molecular medicine have made it possible to develop tools that will facilitate
      a faster and more precise diagnosis of infection. Individual variability between
      each patient's responses to infection can assist in tailoring therapeutic
      interventions to the individual's disease profile and monitoring treatment
      response. In this review, we describe those recent advances in genomics and
      theragnostics, which are slowly entering clinical practice and which will make
      possible a more personalized approach to each septic patient in the next decade.

PMID- 24579692
TI  - Connecting with The Biggest Loser: an extended model of parasocial interaction
      and identification in health-related reality TV shows.
AB  - This study investigates audience responses to health-related reality TV shows in
      the setting of The Biggest Loser. It conceptualizes a model for audience members'
      parasocial interaction and identification with cast members and explores
      antecedents and outcomes of parasocial interaction and identification. Data
      analysis suggests the following direct relationships: (1) audience members'
      exposure to the show is positively associated with parasocial interaction, which
      in turn is positively associated with identification, (2) parasocial interaction
      is positively associated with exercise self-efficacy, whereas identification is
      negatively associated with exercise self-efficacy, and (3) exercise self-efficacy
      is positively associated with exercise behavior. Indirect effects of parasocial
      interaction and identification on exercise self-efficacy and exercise behavior
      are also significant. We discuss the theoretical and practical implications of
      these findings.

PMID- 24579694
TI  - A single-center experience on percutaneously performed partial omentectomy in
      pediatric peritoneal dialysis patients.
AB  - OBJECTIVE: This study describes a single-center experience on percutaneously
      performed partial omentectomy procedure in pediatric peritoneal dialysis (PD)
      patients who showed early catheter dysfunction and required catheter replacement
      due to catheter flow obstruction. MATERIALS AND METHODS: We performed a
      retrospective review of clinical outcomes from pediatric PD patients who
      underwent percutaneous catheter replacement by pediatric nephrologists between
      November 1995 and December 2012. Partial omentectomy was performed in those
      patients in whom omental or adhesion trapping to the catheter tip was seen.
      RESULTS: During the study period, catheter dysfunction that eventually required
      percutaneous catheter replacement occurred in 32 (23.7%) children. Of these, 9
      patients were performed partial omentectomy. Mean age at initiation of PD and
      time of omentectomy was 97.48 +/- 46.06 and 98.53 +/- 45.55 months, respectively.
      Catheter dysfunction appeared after a mean 1.20 +/- 1.0 months. The causes of
      catheter dysfunction were omental wrapping and malposition. No peritonitis
      occurred before omentectomy. Mean total operation time was 60 +/- 8.83 min. No
      complications were encountered during the procedure. After omentectomy, mean
      catheter survival period was 5.92 +/- 6.88 months. A total of five peritonitis
      episodes occurred. Three patients were transferred to hemodialysis. Six patients
      were on PD treatment without any problem at the end of the first year of their
      follow-up. Two patients underwent kidney transplantation. Four patients were
      still on chronic PD treatment at the end of the study period. CONCLUSION: When
      performed by an experienced nephrologist, the performance of partial omentectomy
      by percutaneous route, when required, is an easy, safe and efficient therapeutic
      procedure in children on chronic PD treatment.

PMID- 24579695
TI  - From radiobiology to technology: what is changing in radiotherapy for prostate
      cancer.
AB  - In the last decades, new technologies have been introduced in the daily clinical
      practice of the radiation oncologist: 3D-Conformal radiotherapy (RT) became
      almost universally available, thereafter, intensity modulated RT (IMRT) gained
      large diffusion, due to its potential impact in improving the clinical outcomes,
      and more recently, helical and volumetric arc IMRT with image-guided RT are
      becoming more and more diffused and used for prostate cancer patients. The
      conventional dose-fractionation results to be the best compromise between the
      efficacy and the safety of the treatment, but combining new techniques, modern RT
      allows to overcame one of the major limits of the 'older' RT: the impossibility
      of delivering higher total doses and/or high dose/fraction. The evidences
      regarding radiobiology, clinical and technological evolution of RT in prostate
      cancer have been reported and discussed. 

PMID- 24579693
TI  - Tumour-associated macrophages targeted transfection with NF-kappaB decoy/mannose
      modified bubble lipoplexes inhibits tumour growth in tumour-bearing mice.
AB  - Tumour-associated macrophages (TAM) exhibit an M2 phenotype that promotes tumour
      progression, and conversion of M2 TAM toward a tumouricidal M1 phenotype is a
      promising anti-cancer therapy. As NF-kappaB is a key regulator of macrophage
      polarization, we developed an in vivo TAM-targeting delivery system that combines
      mannose-modified bubble liposomes/NF-kappaB decoy complexes (Man-PEG bubble
      lipoplexes) and ultrasound (US) exposure. We investigated the effects of NF
      kappaB decoy transfection on TAM phenotype in solid tumour-bearing mice. Post
      transfection tumour growth and survival rates were also recorded. Th2 cytokine
      (IL-10) level in TAM was significantly lower by NF-kappaB decoy transfection
      using Man-PEG bubble lipoplexes and US exposure, while Th1 cytokine levels (IL
      1beta, TNF-alpha and IL-6) were significantly higher when compared with controls.
      In addition, mRNA levels of vascular endothelial growth factor, matrix
      metalloproteinase-9 and arginase were significantly lower in TAM post-NF-kappaB
      decoy transfection. Importantly, TAM-targeted NF-kappaB decoy transfection
      inhibited tumour growth and prolonged survival rates in mice. Therefore, TAM
      targeted NF-kappaB decoy transfection using Man-PEG bubble lipoplexes and US
      exposure may be an effective approach for anti-cancer therapy based on TAM
      phenotypic conversion from M2 toward M1.

PMID- 24579696
TI  - A new metric for long-range transport potential of chemicals.
AB  - We propose a new metric for long-range transport potential (LRTP), GIF, based on
      source-receptor analyses and evaluate the LRTP and persistence of a wide variety
      of chlorinated and brominated organic compounds using GIF and overall persistence
      (POV), respectively. We calculated GIF and POV using our global 3D dynamic
      multimedia model (FATE). Physicochemical properties were obtained from
      quantitative structure-property relationship (QSPR) models. The FATE-QSPR
      combined model enabled us to systematically investigate the LRTP and persistence
      of a wide variety of chemical substances. On average, the estimated GIF and POV
      for chlorinated compounds were larger than those for their brominated
      counterparts, with the largest and smallest values found for polychlorinated
      biphenyls and polybrominated dibenzodioxins, respectively. We also compared GIF
      with four differently defined LRTP metrics and two LRTP metrics obtained from a
      simple model. The results of our analyses indicate that the LRTP ranks can differ
      considerably among LRTP metrics, the differences being dependent on the governing
      environmental processes, relevant physicochemical properties, and multimedia
      model. 

PMID- 24579698
TI  - Estimates of sensitivity and specificity of electric pulp testing depend on pulp
      disease spectrum: a modelling study.
AB  - AIM: To demonstrate how the spectrum of diseased pulps may influence sensitivity
      and specificity in diagnostic studies on pulp status. METHODOLOGY: An original
      sample from a previous study consisting of 59 teeth scheduled for root canal
      treatment was used where the relationship between the response to electric pulp
      testing and the visual status of the pulp was evaluated. To alter the spectrum of
      diseased pulps, a hypothetical sample of asymptomatic teeth with deep caries
      lesions was added to the original sample. Sensitivity and specificity were then
      compared for the two samples. RESULTS: In the original sample of 59 teeth,
      sensitivity was 72% and specificity 90%. When the spectrum of diseased pulps was
      altered, sensitivity decreased to 67% and specificity increased to 97%. The
      change in disease spectrum also decreased the prevalence of necrotic pulps.
      CONCLUSIONS: The spectrum of diseased pulps included in a diagnostic study on the
      accuracy of electric pulp testing, and indirectly also disease prevalence (here
      pulp necrosis), influences estimates of sensitivity and specificity. This implies
      that estimates of diagnostic accuracy from one study with a particular tooth
      population spectrum may not apply to another tooth population with a different
      disease spectrum.

PMID- 24579697
TI  - Structure, MC3T3-E1 cell response, and osseointegration of macroporous titanium
      implants covered by a bioactive microarc oxidation coating with microporous
      structure.
AB  - Macroporous Ti with macropores of 50-400 MUm size is prepared by sintering Ti
      microbeads with different diameters of 100, 200, 400, and 600 MUm. Bioactive
      microarc oxidation (MAO) coatings with micropores of 2-5 MUm size are prepared on
      the macroporous Ti. The MAO coatings are composed of a few TiO2 nanocrystals and
      lots of amorphous phases with Si, Ca, Ti, Na, and O elements. Compared to compact
      Ti, the MC3T3-E1 cell attachment is prolonged on macroporous Ti without and with
      MAO coatings; however, the cell proliferation number increases. These results are
      contributed to the effects of the space structure of macroporous Ti and the
      surface chemical feature and element dissolution of the MAO coatings during the
      cell culture. Macroporous Ti both without and with MAO coatings does not cause
      any adverse effects in vivo. The new bone grows well into the macropores and
      micropores of macroporous Ti with MAO coatings, showing good mechanical
      properties in vivo compared to Ti, MAO-treated Ti, and macroporous Ti because of
      its excellent osseointegration. Moreover, the MAO coatings not only show a high
      interface bonding strength with new bones but also connect well with macroporous
      Ti. Furthermore, the pushing out force for macroporous Ti with MAO coatings
      increases significantly with increasing microbead diameter. 

PMID- 24579700
TI  - T-cell immunity to influenza A viruses.
AB  - Influenza infection remains a global threat to human health. Influenza viruses
      are normally controlled by antibodies specific for the surface glycoproteins
      hemagglutinin (HA) and neuraminidase (NA). Standard influenza vaccines are aimed
      at inducing these antibodies, but they must be administered annually and can be
      rendered ineffective since different strains circulate from year to year and vary
      considerably in their individual HA and NA profiles. Influenza-specific T cells
      have been shown to be protective in animal models and typically recognize the
      more conserved internal influenza proteins. Improving our understanding of
      influenza-specific T-cell responses, including immunodominance, specific epitope
      sequences, strain-related epitope variation, host/virus interaction, and the
      balance between immunity versus immunopathology, will be important to improve
      future T-cell-based vaccines, which promise broader strain coverage and longer
      lasting protection than current standard vaccines. 

PMID- 24579701
TI  - The inflammasome and its regulation.
AB  - Inflammasomes, multiprotein platforms of caspase-1 activation, are assembled in
      response to a number of exogenous and endogenous danger signals, leading to the
      production of pro-inflammatory cytokines and induction of inflammatory cell death
      through the activation of caspase-1. Inflammasomes have been implicated in a wide
      range of physiological and pathological processes, including host defense against
      microbial pathogens, maintenance of intestinal homeostasis, and even development
      of inflammatory disorders. Thus, inflammasomes can be both beneficial and
      detrimental, and understanding the mechanisms involved in inflammasome activation
      may provide a better approach to prevent the harmful effects of the inflammatory
      response. Although inflammasome complexes are formed via protein-protein
      interactions between their components, accumulating evidence suggests that
      inflammasome activation is positively and negatively regulated by ligand-binding
      receptors, accessory proteins, other caspases, cytokines, kinases/phosphatases,
      redox sensors, ion homeostasis, second messengers, organelles, cytoskeleton, and
      autophagy, among others. Moreover, inflammasome activation can result in the
      formation of another caspase-1-activating protein complex, the ASC
      speck/pyroptosome, which is also tightly controlled. In this review, we discuss
      how the assembly of inflammasomes and ASC speck is regulated by complex
      mechanisms. Recent findings on effector functions and biological roles of
      inflammasomes also are summarized. 

PMID- 24579699
TI  - Changes in adipose tissue macrophages and T cells during aging.
AB  - Adipose tissue historically was believed to be an inert tissue, functioning
      primarily in the storage of energy and thermal homeostasis. However, recent
      discoveries point toward a critical role for adipocytes in endocrine function as
      well as immune regulation. Excess body fat, accumulated through aging and/or a
      calorie-rich diet, is associated with many chronic metabolic and inflammatory
      diseases. Within the stromal vascular fraction of adipose tissue, macrophages and
      T cells accumulate with increasing tissue mass, secreting pro- or anti
      inflammatory cytokines. In this review we discuss the current understanding of
      immune cell function in both diet-induced and age-related obesity. In both models
      of obesity, the classically activated, pro-inflammatory (M1) subtype takes
      precedence over the alternatively activated, anti-inflammatory (M2) macrophages,
      causing tissue necrosis and releasing pro-inflammatory cytokines like interleukin
      6. Other distinct adipose tissue macrophage subtypes have been identified by
      surface marker expression and their functions characterized. Adipose tissue T
      cell recruitment to adipose tissue is also different between aging- and diet
      induced obesity. Under both conditions, T cells exhibit restricted T-cell
      receptor diversity and produce higher levels of pro-inflammatory signals like
      interferon-gamma and granzyme B relative to young or healthy mice. However,
      numbers of regulatory T cells are dramatically different between the 2 models of
      obesity. Taken together, these findings suggest models of age- and diet-induced
      obesity may be more distinct than previously thought, with many questions yet to
      be resolved in this multidimensional disease. 

PMID- 24579703
TI  - Influence of local climate and climate change on aeroterrestrial phototrophic
      biofilms.
AB  - Aeroterrestrial phototrophic biofilms colonize natural and man-made surfaces and
      may damage the material they settle on. The occurrence of biofilms varies between
      regions with different climatic conditions. The aim of this study was to evaluate
      the influence of meteorological factors on the growth of aeroterrestrial
      phototrophs. Phototrophic biomass was recorded on roof tiles at six sites within
      Germany five times over a period of five years and compared to climatic
      parameters from neighboring weather stations. All correlating meteorological
      factors influenced water availability on the surface of the roof tiles. The
      results indicate that the frequency of rainy days and not the mean precipitation
      per season is more important for biofilm proliferation. It is also inferred that
      the macroclimate is more important than the microclimate. In conclusion, changed
      (regional) climatic conditions may determine where in central Europe global
      change will promote or inhibit phototrophic growth in the future.

PMID- 24579702
TI  - iNKT cells: innate lymphocytes with a diverse response.
AB  - It is now established that natural killer T (NKT) cells can influence adaptive
      immune responses by producing vast amounts of cytokines. Different subsets of NKT
      cells with distinctive functional characteristics regarding cytokine production
      have been described. This is the case for NKT1, NKT2, or NKT17 that resemble
      conventional CD4 Th1, Th2, and Th17 cells in the cytokines they produce. Unlike
      conventional CD4 T cells that mostly acquire functional specialization in the
      periphery, a number of NKT cells become specialized effectors during thymic
      development. This opinion article describes the evidence for an extrathymic
      commitment of specialized NKT-cell subsets that, together with thymic lineages,
      contributes to the overall functional diversity of NKT cells participating in
      immune responses in the periphery. 

PMID- 24579706
TI  - On the shoulders of younger giants public health nursing moves forward.

PMID- 24579704
TI  - A three-dimensionally engineered biomimetic cartilaginous tissue model for
      osteoarthritic drug evaluation.
AB  - Osteoarthritis (OA) is primarily characterized by focal cartilage destruction and
      synovitis. Presently, the pathogenesis of OA remains unclear, and an effective
      treatment methodology is an unmet need. To this end, a plethora of animal models
      and monolayer models have been developed, but they are faced with the limitation
      of high cost and inability to recapitulate a pure hyaline cartilaginous
      phenotype, which is important in studying the efficacy of therapeutic agents. We
      have previously developed a living hyaline cartilage graft (LhCG) that accurately
      presented a pure hyaline cartilage phenotype. Here, through the coculture of
      lipopolysaccharide (LPS)-activated macrophages with LhCG, we hypothesized that an
      accurate OA disease model may be developed. Subsequently, this model was
      evaluated for its accuracy for in vitro drug testing. Results indicated that
      chondrocyte proliferation and apoptosis were increased in the disease model.
      Additionally, extracellular matrix (ECM) synthesis increased as indicated by the
      increased anabolic gene expression levels, such as collagen type II and aggrecan.
      Up-regulation of matrix metalloproteinase-1 (MMP-1) and MMP-3 genes suggested
      increased degradative activity, while chondrocytic hypertrophic differentiation
      was observed. Furthermore, extensive degradation of collagen type II and
      glycosaminoglycans (GAGs) were also observed. The results of celecoxib treatment
      on our model showed inhibition of nitric oxide (NO) and prostaglandin E2 (PGE2)
      production, as well as down-regulation of MMP-1 and MMP-3 expression. Taken
      together, the results suggested that this coculture model was able to
      sufficiently mimic the native, diseased OA cartilage, while drug testing results
      confirmed its suitability as an in vitro model for predicting native cartilage
      response to drug treatment. 

PMID- 24579708
TI  - Population density, distance to public transportation, and health of women in low
      income neighborhoods.
AB  - OBJECTIVES: The purpose of this research was to determine the impact of two
      neighborhood walkability (the extent to which the built environment is pedestrian
      friendly) metrics on health outcomes of women living in low-income urban
      neighborhoods, both before and after accounting for individual and neighborhood
      factors. DESIGN AND SAMPLE: A cross-sectional, retrospective design was used. The
      sample of 1800 low-income women was drawn from Welfare, Children and Families: A
      Three-City Study (a study of low-income women from three U.S. cities). MEASURES:
      Using multilevel modeling and geographic information systems, the study sought to
      determine the effect of distance to public transportation and residential density
      on health status, mental health symptoms, and health-related limitations.
      RESULTS: No significant relationship was found between the two walkability
      metrics and health outcomes. Instead, neighborhood problems that affect crime and
      safety impacted health status and mental health symptoms. CONCLUSIONS: As cities
      make changes to the built environment with the hope of affecting residents'
      health outcomes, public health nurses need to be aware that changing walkability
      characteristics in a neighborhood may not affect the health of residents of high
      crime, low-income neighborhoods. Without first addressing neighborhood crime,
      efforts to improve walkability in low-income neighborhoods may fail.

PMID- 24579709
TI  - Factors associated with health promotion in megachurches: implications for
      prevention.
AB  - OBJECTIVE: Megachurches (churches with 2,000 + attendance) represent a community
      institution with extensive reach within the United States population, although
      little is known about their health and wellness programming (HWP). The purpose of
      this study was to examine factors associated with HWP in megachurches. DESIGN AND
      SAMPLE: Staff at megachurches were recruited to take an online survey. MEASURES:
      Questions addressed HWP, church demographics, health promotion-related beliefs,
      barriers, existing resources, and leader involvement (response rate 15.4%).
      Univariate and multiple regression analyses were used to examine influences on
      HWP. RESULTS: Respondents (n = 110 churches) indicated that churches were
      primarily Baptist (23.6%) or Nondenominational (21.1%), had 2,500-4,999
      congregation members (44.5%), primarily White congregation members (83.5%), and
      31-60 employees (45.4%). More positive leader, advisory board, and church member
      perceptions of health and wellness, a supportive church doctrine for health,
      leader involvement in HWP, and the number of health-related and physical activity
      resources were positively associated with HWP (p < .05). Reporting fewer barriers
      was positively associated with HWP. The full regression model explained 56% of
      the variance in HWP, with number of health resources and church size as positive
      influences. CONCLUSIONS: Targeting the social environment for health,
      implementing health-related policies and environmental changes could result in
      successful interventions for preventing chronic disease.

PMID- 24579710
TI  - Differences between dementia caregivers who are users and nonusers of community
      services.
AB  - OBJECTIVES: To examine differences between users and non-users of community
      services in caregivers of persons with dementia (PWD). A profile of who used
      services versus did not use services was developed. DESIGN AND SAMPLE: Existing
      cross-sectional data from the NINR funded National Caregiver Training Project
      (data collected 1995-1997) were used. The sample (N = 241) of caucasian, well
      educated caregivers reflected a mix of spouse and adult caregivers with a mean
      age of 64.8 years. MEASURES: Variables measured included caregiver social
      support, burden, and depression as well as problem behavior of PWD. RESULTS: The
      majority of caregivers did not attend support groups (73%) or use respite
      services (79%). Among caregivers who did not use services, 78% lived with the
      recipient and 77% were spouses. The profile of non-users compared to users
      revealed that non-users were significantly older, more depressed, and received
      less social support. On the other hand, non-users provided fewer hours of care
      per week to recipients who had less cognitive and functional deterioration and
      fewer behavior problems. CONCLUSIONS: These findings provide public health nurses
      with knowledge about service use in caregivers of PWD. Recommendations regarding
      caregiver needs for assistance and increased use of services before a crisis
      ensues are presented.

PMID- 24579711
TI  - Building from within: pastoral insights into community resources and assets.
AB  - OBJECTIVES: To explore perceptions of community pastors regarding the extent of
      community resources and assets in a rural, Southern, African American community.
      DESIGN AND SAMPLE: Utilizing a qualitative, descriptive design, interviews were
      conducted with six African American pastors. MEASURES: Interviews were conducted
      using a semi-structured interview guide based on an assets-oriented approach.
      RESULTS: Pastors discussed various resources and assets, probable within the
      community that may be considered as support for program development. Key themes
      included: (1) community strengths, (2) community support, and (3) resources for a
      healthy lifestyle. The church was identified, throughout the interviews, as a
      primary source of strength and support for community members. CONCLUSIONS: In
      this study of African American pastors, various perceptions of community
      resources were identified. Findings indicate that a sample, rural, Southern,
      African American community has a wealth of resources and assets, but additional
      resources related to health promotion are still necessary to produce optimal
      results. Specific programs to prevent chronic conditions such as cardiovascular
      disease can provide an effective means for addressing related health disparities.
      Programs implemented through churches can reach large numbers of individuals in
      the community and provide an important source of sustainable efforts to improve
      the health of African Americans.

PMID- 24579713
TI  - Teaching/learning strategies for the essentials of baccalaureate nursing
      education for entry-level community/public health nursing.
AB  - The purpose of this article is to describe teaching/learning strategies for each
      of the 15 Essentials of Baccalaureate Nursing Education for Entry-Level
      Community/Public Health Nursing (ACHNE, 2009). Carper's ways of knowing serve as
      foundations for creating classroom and clinical experiences that focus on
      clinical action with community as client. Each community/public health essential
      is defined with relevance to community/public health nursing practice. Five
      teaching/learning strategies have been delineated for each essential with
      suggestions of teaching resources and/or target population application.
      Teaching/learning strategies that focus on community as client, population
      health, and the essential knowledge and competencies of C/PH nursing will help
      ensure preparation of baccalaureate prepared nurses with knowledge and skills to
      improve the health of populations.

PMID- 24579712
TI  - The Quad Council practice competencies for public health nursing.
AB  - This article describes the most recent efforts by the Quad Council of Public
      Health Nursing organizations to review and revise the competencies for PHN
      practice, and highlights the implications of these competencies for practice,
      education, and research. The Quad Council is a coalition of four nursing
      organizations with a focus on public health nursing and includes the Association
      of Community Health Nursing Educators; the Association of Public Health Nursing
      (known prior to July 1, 2012 as the Association of State and Territorial
      Directors of Nursing); the Public Health Nursing section of the American Public
      Health Association; and the Council on Economics and Practice of the American
      Nurses' Association. The Quad Council competencies are based on the Council on
      Linkages competencies for public health professionals and were designed to ensure
      that public health nursing fits in the domain of public health science and
      practice.

PMID- 24579714
TI  - Development and evaluation of an international service learning program for
      nursing students.
AB  - OBJECTIVES: (1) Using Riner's framework, the development of an international
      service learning program in the Dominican Republic (DR) for Baccalaureate nursing
      students will be described, and (2) an initial impact of the students'
      experiences will be examined. DESIGN AND SAMPLE: A qualitative descriptive
      research design was used to examine its impact. The international service
      learning program included (1) didactic (five, 2 hr and one full day educational
      sessions) prior to (2) immersion (2 weeks in country), and (3) posttrip
      debriefing session. Ten females, senior nursing students participated in the
      program. Students' daily journals were examined using thematic analysis. RESULTS:
      Five major themes that emerged were as follows adapting physically, encountering
      frustration in their inability to fully meet patients' needs, increasing
      confidence in speaking Spanish and assessing health problems, and increasing
      cultural awareness. Students were descriptive regarding their daily activities,
      and did some, but limited, critical reflection. CONCLUSIONS: Models of reflection
      need to be explored to select the most appropriate technique to facilitate
      students' critical reflection in meeting the goals and objectives of the
      experience. Curriculum integration of global learning, social consciousness, and
      global cultural competence development is needed.

PMID- 24579715
TI  - Embracing a competency-based specialty curriculum for community-based nursing
      roles.
AB  - The Quad Council competencies for public health nursing (PHN) provide guidance in
      developing curricula at both the generalist and specialist level. However, these
      competencies are based on nursing roles in traditional public health agencies and
      community/public health is defined more broadly than official agency practice.
      The question arises as to whether community-based specialties require largely the
      same knowledge and skill set as PHN. The purpose of the competency cross-mapping
      project reported here was to (a) assess the intersection of the Quad Council
      competencies with four community-based specialties and (b) ensure the
      appropriateness of a Quad Council-based curriculum to prepare graduates across
      these four specialties (home health, occupational health, environmental health,
      and school nursing). This article details the multistep cross-mapping process,
      including validation with practice leaders. Results indicate strong alignment of
      community-based specialty competencies with Quad Council competencies. Community
      based specialty-specific content that did not align well is identified, along
      with examples of didactic and clinical strategies to address gaps. This work
      indicates that a Quad Council-based curriculum is appropriate to prepare
      graduates in community-based specialties when attention to the specialty-specific
      competencies in the clinical setting is included. This work guides the
      development of a doctorate of nursing practice curriculum in PHN, encompassing
      the four additional community-based specialties.

PMID- 24579717
TI  - The experience of living with metastatic breast cancer--a review of the
      literature.
AB  - Women's experiences with metastatic breast cancer have received little research
      attention. We reviewed published articles (1984-2013) reporting research
      examining women's experiences of metastatic breast cancer (n = 33). Findings from
      quantitative studies were categorized into three broad areas: adverse
      consequences, satisfaction with health care providers, and strategies for living.
      Themes identified from qualitative findings include living as a social outsider;
      importance of hope; health and quality of life; positive experiences; experiences
      at end of life; and strategies for living. More research is needed to explore
      experiences of subgroups to appropriately respond to women's diverse care needs. 

PMID- 24579716
TI  - Public health nursing competency instrument: scale reduction and reliability of
      factors.
AB  - OBJECTIVES: To reduce the number of items of the Public Health Nursing Competency
      Instrument (PHNCI) and to report the psychometric properties of the abbreviated
      instrument. DESIGN AND SAMPLE: The 193-item PHNCI was administered via an online
      survey tool. A national sample of 2,269 public health nurses was recruited from
      25 states. MEASURES: All items of the PHNCI scale were positively stated and
      participants were asked to rate their skill level via a 4-point Likert scale.
      RESULTS: A principal component exploratory factor analysis with oblique rotation
      and examination of scree plot resulted in a final abbreviated scale which
      included 81 items and six factors: (1) Evaluation Competencies, (2)
      Individual/Family/Community Competencies, (3) Systems' Competencies, (4)
      Partnership/Collaboration Competencies, (5) Planning Competencies, and (6)
      Assessment Competencies. The six factors in the resulting PHNCI Abbreviated
      (PHNCIa ) demonstrated acceptable internal consistency, ranging from 0.92 to
      0.98. CONCLUSION: The six factors of the PHNCIa integrate important concepts of
      both the nursing process and the intervention wheel. The instrument can be used
      by educators, administrators, managers, and staff members to assess strengths and
      challenge areas, guide discussions on performance and expectations, and enhance
      professional development efforts. Next steps for future research are presented.

PMID- 24579719
TI  - Hope of rural women caregivers of persons with advanced cancer: guilt, self
      efficacy and mental health.
AB  - INTRODUCTION: Caring for a person with advanced disease can have a detrimental
      impact on the quality of life of family caregivers. This is further compounded in
      rural areas that have few or no palliative care services. Hope has a positive
      influence on the quality of life of family caregivers of persons with advanced
      cancer but factors influencing hope specifically in rural women caregivers of
      persons with advanced cancer have not been examined. PURPOSE: The purpose of this
      study was to determine factors influencing the hope of rural women caring for
      persons with advanced cancer, by examining the relationship of hope with
      demographic variables, self-efficacy, guilt, and caregiver physical and mental
      health. METHODS: A cross-sectional prospective correlational design was used.
      Inclusion criteria for the study were: (a) female, (b) 18 years of age or older,
      (c) caring for a person diagnosed with advanced cancer, (d) home address with a
      rural postal code, and (e) English-speaking. Using a modified Dillman technique,
      surveys and an invitation to participate were mailed to 780 persons with advanced
      cancer living in rural areas using two western Canadian provincial cancer
      registries. A reminder card was sent 4 weeks later. The persons with advanced
      cancer were asked to give the survey to their primary caregiver to complete.
      Surveys included measures of hope (Herth Hope Index (HHI)), general self-efficacy
      (General Self-Efficacy Scale (GSES)), grief (Non Death Version Revised Grief
      Experience Inventory (NDRGEI)), mental and physical health (Short Form Health
      Survey Version 2 (SF-12v2)), and demographic data such as their relationship to
      the person for whom the caregiver was caring. Data were entered into the
      Statistical Package for the Social Sciences v19 (SPSS) and analyzed using
      generalized linear modeling. RESULTS: Significant factors (p <= 0.05) influencing
      HHI scores were GSES ( p <= 0.0001), NDRGEI subscale (p=0.001), and SF-12v2
      mental health summary scores (p=0.002). Participants with higher GSES, lower
      NDRGEI, and higher SF-12v2 mental health summary scores had higher HHI scores.
      The SF-12v2 physical health summary mean score of 43.30 (standard deviation
      (SD)=4.63) was below the 25th percentile (46.53) of US population norms. The SF
      12v2 mental health summary mean score of 45.24 (SD=5.98) was just above the 25th
      percentile of US population norms (45.13). CONCLUSION: Participants with higher
      hope scores had higher mental health scores, lower perceptions of loss and grief
      scores, and higher scores in their confidence in their ability to deal with
      difficult situations (self-efficacy). The significant relationships found between
      hope and mental health, general self-efficacy, and perceptions of guilt provide a
      foundation for future research and underscore the importance of hope to rural
      women caregivers. The low physical and mental health scores of rural women
      caregivers are of concern and highlight the need to support this population.

PMID- 24579720
TI  - Novel monoclonal antibodies for therapy of multiple sclerosis.
AB  - INTRODUCTION: Monoclonal antibodies play an important role in the therapy of
      different autoimmune diseases. With the introduction of natalizumab, the
      importance of monoclonal antibodies in the therapy of multiple sclerosis (MS) has
      dramatically increased during the past years. AREAS COVERED: In this review, we
      will focus on newly approved and emerging antibodies for MS therapy. Based on
      published original articles and citable meeting abstracts, we will discuss their
      mode of action as well as data on efficacy and safety. EXPERT OPINION:
      Natalizumab was a breakthrough in MS therapy. However, side effects of this
      monoclonal antibody limit its use. The risk/benefit ratios of new biologicals in
      MS therapy are not yet clear. High-yield process daclizumab might qualify as
      first-line MS therapy, unless hepatotoxicity becomes a relevant safety concern.
      Alemtuzumab has been approved for MS therapy in Europe but will be reserved for
      selected patients with highly active disease due to frequent induction of
      potentially dangerous secondary autoimmune phenomena. Ocrelizumab will likely
      also be licensed as a second-line therapy in highly active MS. Neutralizing
      antibodies to interleukin (IL)-17A and blocking antibodies to leucine rich repeat
      and Ig domain containing 1 might be the most interesting upcoming new antibodies
      as both offer a new and pathophysiologically relevant approach in MS therapy.

PMID- 24579722
TI  - Examining the structure, reliability, and validity of the Chinese personal growth
      initiative scale-II: evidence for the importance of intentional self-change among
      Chinese.
AB  - We examined the factor structure, reliability, and validity of the Chinese
      version of the Personal Growth Initiative Scale-II (CPGIS-II) using data from a
      sample of 927 Chinese university students. Consistent with previous findings,
      confirmatory factor analyses supported a 4-factor model of the CPGIS-II.
      Reliability analyses indicated that the 4 CPGIS-II subscales, namely Readiness
      for Change, Planfulness, Using Resources, and Intentional Behavior, demonstrated
      good internal consistency reliability and adequate test-retest reliability across
      a 4-week period. In addition, evidence for convergent and incremental validity
      was found in relation to measures of positive and negative psychological
      adjustment. Finally, results of hierarchical regression analyses indicated that
      the 4 personal growth initiative dimensions, especially planfulness, accounted
      for additional unique variance in psychological adjustment beyond resilience.
      Some implications for using the CPGIS-II in Chinese are discussed. 

PMID- 24579723
TI  - Visual sensory and perceptive functioning in 5-year-old very preterm/very-low
      birthweight children.
AB  - AIM: To examine visual sensory and perceptive functions, study their
      interrelations, and explore associations between visual dysfunctions and
      intelligence in very preterm/very-low-birthweight (VP/VLBW) children. METHOD: One
      hundred and sixteen VP/VLBW children (57 males, 59 females; mean gestational age
      30.1 wks, SD 2.3; mean corrected age 5 y 6 mo, SD 1 mo) and 73 term-born children
      (40 males, 33 females; mean gestational age 39.9 wks, SD 1.3; mean age 5 y 6 mo,
      SD 3 mo) completed visual sensory (acuity, visual field, contrast-, color-, and
      stereovision), perceptive (visual coherence, and Developmental Test of Visual
      Perception non-motor scale), and intelligence assessments. RESULTS: Compared with
      term-born children, VP/VLBW children had reduced acuity (d=0.70, p<0.001),
      inferior visual field (d=0.67, p<0.001), and stereovision (v=0.19, p=0.008).
      VP/VBLW children showed weaker static coherence (d=0.49, p=0.001) and Position in
      Space (d=0.41, p=0.006) performance, independent of visual sensory deficits, and
      showed lower Verbal IQ (VIQ) and Performance IQ (PIQ; p<0.001). Visual perceptive
      functioning accounted for 13% of variance in VIQ, and for 35% of variance in PIQ.
      INTERPRETATION: Visual sensory and perceptive dysfunctions are present in VP/VLBW
      children and occur largely independently of each other. Visual perceptive
      dysfunctions are moderately associated with PIQ, and weakly with VIQ.

PMID- 24579721
TI  - BLUF domain function does not require a metastable radical intermediate state.
AB  - BLUF (blue light using flavin) domain proteins are an important family of blue
      light-sensing proteins which control a wide variety of functions in cells. The
      primary light-activated step in the BLUF domain is not yet established. A number
      of experimental and theoretical studies points to a role for photoinduced
      electron transfer (PET) between a highly conserved tyrosine and the flavin
      chromophore to form a radical intermediate state. Here we investigate the role of
      PET in three different BLUF proteins, using ultrafast broadband transient
      infrared spectroscopy. We characterize and identify infrared active marker modes
      for excited and ground state species and use them to record photochemical
      dynamics in the proteins. We also generate mutants which unambiguously show PET
      and, through isotope labeling of the protein and the chromophore, are able to
      assign modes characteristic of both flavin and protein radical states. We find
      that these radical intermediates are not observed in two of the three BLUF
      domains studied, casting doubt on the importance of the formation of a population
      of radical intermediates in the BLUF photocycle. Further, unnatural amino acid
      mutagenesis is used to replace the conserved tyrosine with fluorotyrosines, thus
      modifying the driving force for the proposed electron transfer reaction; the rate
      changes observed are also not consistent with a PET mechanism. Thus, while
      intermediates of PET reactions can be observed in BLUF proteins they are not
      correlated with photoactivity, suggesting that radical intermediates are not
      central to their operation. Alternative nonradical pathways including a keto-enol
      tautomerization induced by electronic excitation of the flavin ring are
      considered. 

PMID- 24579724
TI  - Nephroprotective potential of selenium and taurine against mercuric chloride
      induced nephropathy in rats.
AB  - The study was aimed to estimate whether pre-treatment with sodium selenite or
      taurine would reverse kidney damage induced by intraperitoneal injection of
      mercuric chloride in rats. Animals were divided into six groups: (1) control
      group; (2) sodium selenite group; (3) taurine group; (4) HgCl2 group; (5) sodium
      selenite pretreated group; (6) taurine pretreated group. The results demonstrated
      that HgCl2 causes significant enhancement in serum malondialdehyde (MDA),
      creatinine, N-acetyl-beta-d-glucosaminidase (NAG), cystatin C, nephrin and
      interleukin 6 (IL-6) levels accompanied with significant reduction in serum
      nitric oxide (NO) level. Pretreatment with sodium selenite or taurine produces
      significant depletion in MDA, NAG, cystatin C, nephrin and IL-6 levels in
      concomitant with significant elevation in serum NO level as compared to HgCl2
      group. HgCl2 induced pathological alterations in the kidney. The ultrastructural
      investigation of renal cortex of HgCl2-administered group revealed that the
      glomerular basement membrane is uniform, the fenestrations of endothelial cells
      are swollen, and the secondary foot processes appear also swollen even fused at
      some points. The proximal convoluted tubules showed apical short and few
      microvilli, while, some tubular cells showed relatively normal microvilli. In
      contrast, sodium selenite or taurine pretreatment could significantly reduce the
      pathological alterations in the kidney caused by HgCl2 intoxication. The current
      results suggested that selenium and taurine possess nephroprotective efficacy due
      to their antioxidative capacity and anti-inflammatory activity.

PMID- 24579727
TI  - Hydration dynamics of cyanoferrate anions examined by ultrafast infrared
      spectroscopy.
AB  - In this work, we carried out steady-state IR absorption, transient IR pump-probe,
      and waiting-time-dependent two-dimensional (2D) IR measurements on ferrocyanide
      and ferricyanide ions solvated in water and deuterated water. These two anions
      are highly symmetric and have distributed cyano groups with IR-active stretching
      modes in the 5 MUm wavelength region. The line width of their linear IR spectra
      and the initial value of the vibrational frequency-frequency correlation function
      extracted from their 2D IR spectra indicate water molecules in the hydration
      shell of the ferro-species are more inhomogeneously distributed but more tightly
      bound to the cyano groups than those of the ferri-species. Different charges and
      their distributions in the two anions cause different hydrogen bonding strengths
      with solvent. The frequency correlation relaxes somewhat slower in ferrocyanide,
      agreeing with stronger solute-solvent hydrogen-bonding interaction in this case.
      Mechanisms of the solvent isotope effect on the vibrational relaxation dynamics
      of the cyano stretching mode are discussed. These results also suggest that in
      the hydration shell the ferro-species breaks more water structure than the ferri
      species, which is opposite to the situation of the bulk water region (beyond the
      hydration shell) reported previously. This work demonstrated that combined IR
      methods can be very useful for understanding the molecular details of the
      structure and dynamics of the hydrated ions. 

PMID- 24579728
TI  - Identification of synthetic steroids in river water downstream from
      pharmaceutical manufacture discharges based on a bioanalytical approach and
      passive sampling.
AB  - A bioanalytical approach was used to identify chemical contaminants at river
      sites located downstream from a pharmaceutical factory, where reproductive
      alterations in wild fish have been previously observed. By using polar organic
      compound integrative samplers (POCIS) at upstream and downstream sites,
      biological activity profiles based on in vitro bioassays revealed the occurrence
      of xenobiotic and steroid-like activities, including very high glucocorticoid,
      antimineralocorticoid, progestogenic and pregnane X receptor (PXR)-like
      activities (MUg standard-EQ/g of sorbent range), and weak estrogenic activity (ng
      E2-EQ/g of sorbent range). Chemical analyses detected up to 60 out of 118
      targeted steroid and pharmaceutical compounds in the extracts. In vitro profiling
      of occurring individual chemicals revealed the ability of several ones to act as
      agonist and/or antagonist of different steroids receptors. Mass balance
      calculation identified dexamethasone, spironolactone, and 6-alpha
      methylprednisolone as major contributors to corticosteroid activities and
      levonorgestrel as the main contributor to progestogenic activities. Finally, RP
      HPLC based fractionation of POCIS extracts and testing activity of fractions
      confirmed identified compounds and further revealed the presence of other unknown
      active chemicals. This study is one of the first to report environmental
      contamination by such chemicals; their possible contribution to in situ effects
      on fish at the same site is suggested. 

PMID- 24579730
TI  - Preface: aging and oncogenesis.

PMID- 24579729
TI  - Crystallization and phase changes in paracetamol from the amorphous solid to the
      liquid phase.
AB  - For the case of paracetamol, we show how terahertz time-domain spectroscopy can
      be used to characterize the solid and liquid phase dynamics. Heating of
      supercooled amorphous paracetamol from 295 K in a covered sample under vacuum
      leads to its crystallization at 330 K. First, form III is formed followed by the
      transformation of form III to form II at 375 K, to form I at 405 K, and finally
      melting is observed around 455 K. We discuss the difference between the
      featureless spectra of the supercooled liquid and its liquid melt. Lastly, we
      studied the onset of crystallization from the supercooled liquid in detail and
      quantified its kinetics based on the Avrami-Erofeev model. We determined an
      effective rate constant of k = 0.056 min(-1) with a corresponding onset of
      crystallization at T = 329.5 K for a heating rate of 0.4 K min(-1). 

PMID- 24579725
TI  - Bright building blocks for chemical biology.
AB  - Small-molecule fluorophores manifest the ability of chemistry to solve problems
      in biology. As we noted in a previous review (Lavis, L. D.; Raines, R. T. ACS
      Chem. Biol. 2008, 3, 142-155), the extant collection of fluorescent probes is
      built on a modest set of "core" scaffolds that evolved during a century of
      academic and industrial research. Here, we survey traditional and modern
      synthetic routes to small-molecule fluorophores and highlight recent biological
      insights attained with customized fluorescent probes. Our intent is to inspire
      the design and creation of new high-precision tools that empower chemical
      biologists. 

PMID- 24579731
TI  - Immunosenescence and cancer.
AB  - The immune system, interacting intimately with the cancer cells in a tumor, may
      combat or favor cancer development and progression, or both. One of the most
      important risk factors for solid cancers is age. With increasing age, numerous
      alterations at multiple levels including molecular, cellular, organ, and systemic
      are occurring. With age many physiological systems are changing, including the
      immune system. Several alterations occur in both arms of the immune system with
      aging. Although the innate immune system shows changes with aging, the most
      important alterations occur in the adaptive immune system, especially involving T
      cells. Many changes in the immune system may decrease its capacity to combat the
      emerging or progressing tumor. Further, the age-related immune changes may favor
      the cancer development. The most important changes which may decrease the immune
      response efficiency are the changes in T cell functions and phenotypes,
      concomitant with the presence of a low-grade inflammation. A consensus is now
      emerging in oncology that not only the cancer cells themselves should be studied
      but also their macro- and microenvironments. In this context, the study of the
      interrelation of the immune response and the tumor at various stages is essential
      to enhance our capacity for intervention in elderly cancer patients. 

PMID- 24579732
TI  - Metabolic syndrome, aging, and cancer.
AB  - Older patients present with an average of three comorbidities beside their
      cancer. One of the most frequent age-associated comorbidities is the metabolic
      syndrome. In the USA, its prevalence is greater than 40% in subjects above the
      age of 60. The metabolic syndrome is associated with an increased risk of cancer
      across multiple tumor types. It also worsens the prognosis of those cancers,
      increasing both their relapse and death rates. In this review, we assess the
      possible mediating mechanisms of this association. The evidence points toward a
      key role of hyperinsulinemia itself, and notably its impact on
      metabolic/proliferation pathways involving mTOR. We will review current
      therapeutic trials that are specifically targeting these pathways, and draw some
      parallels with the use of some of these same agents in animal aging studies. 

PMID- 24579734
TI  - Senescence and the pro-tumorigenic stroma.
AB  - Hayflick and Moorhead first described senescence in the late 1960's as a
      permanent growth arrest that primary cells underwent after a defined number of
      cellular divisions in culture. This observation gave rise to the hypothesis that
      cells contained an internal counting mechanism that limited cellular division and
      that this limit was an important barrier to cellular transformation. What began
      as an in vitro observation has led to an immense body of work that reaches into
      all fields of biology and is of particular interest in the areas of aging, tissue
      regeneration, and tumorigenesis. The initially simplistic view that senescence
      limits cellular division and contributes to aging while stymying tumorigenesis
      has now evolved into an important and complex biological process that has
      numerous caveats and often opposing effects on tumorigenesis. In this review, we
      limit our discussion to the complex role senescence plays in tumorigenesis.
      Throughout the review we attempt to draw many parallels to other systems
      including the role senescent cells play in the tumor microenvironment and their
      significant molecular and phenotypic similarities to cancer associated
      fibroblasts (CAFs). 

PMID- 24579733
TI  - Sirtuins in hematological aging and malignancy.
AB  - Aging of the hematological system causes anemia, reduced immunity, and increased
      incidence of hematological malignancies. Hematopoietic stem cells (HSCs) play a
      crucial role in this process as their functions decline during aging. Sirtuins
      are a family of protein lysine modifying enzymes that have diverse roles in
      regulating metabolism, genome stability, cell proliferation, and survival, and
      have been implicated in mammalian aging and longevity. Here we provide an updated
      overview of sirtuins in aging research; particularly, how increased activity of
      SIRT1, SIRT3, or SIRT6 improves several aging parameters, and may possibly
      increase lifespan in mice. We review the literature on how sirtuins may play a
      role in HSC aging and hematological malignancies, and how key signaling pathways
      of HSCs may be affected by sirtuins. Among them, SIRT1 plays a critical role in
      chronic myelogenous leukemia, an age-dependent malignancy, and inhibition of
      SIRT1 sensitizes leukemic stem cells to tyrosine kinase inhibitor treatment and
      blocks acquisition of resistant oncogene mutations. In-depth understanding of
      sirtuins in HSC aging and malignancy may help design novel strategies to deter
      hematological aging and improve treatment of hematological malignancies. 

PMID- 24579738
TI  - pH independent nano-optode sensors based on exhaustive ion-selective nanospheres.
AB  - Bulk optode-based ion selective optical sensors work on the basis of extraction
      equilibria, and their response toward the analyte ion is known to dependent on
      the sample pH. This pH dependence has been one of the major disadvantages that
      have hampered the broad acceptance of bulk optodes in chemical sensing. We
      present here for the first time the use of exhaustive Ca(2+)-selective
      nanosensors that may overcome this pH dependent response. The nanosensors were
      characterized at different pH and the same linear calibration was obtained in the
      Ca(2+) concentration range from 10(-7) M to 10(-5) M. 

PMID- 24579736
TI  - Optimization of immunotherapy in elderly cancer patients.
AB  - Increasing evidence has revealed the incidence of cancer augments with aging,
      which could be attributed to a multitude of age-associated changes including the
      dysregulation of the immune system. Although many reports demonstrate the
      efficacy of cancer immunotherapies in numerous preclinical studies, most
      experiments have been performed in young animals. Studies from our group and
      others show that cancer immunotherapy could be ineffective in old mice, even
      though the same therapeutic treatment works efficiently in young mice. Given that
      cancer occurs mostly in the elderly, we should take age-associated immune
      dysregulation into consideration to achieve the effectiveness of
      immunotherapeutic interventions in the old. Understanding both age-related and
      tumor-related immune alterations might be equally important in improving the
      effectiveness of immunotherapy. This article reviews a number of age-associated
      immune alterations with specific attention given to the impact on antitumor
      responses, and also discusses possible strategies for optimization of
      immunotherapeutic interventions in the elderly. 

PMID- 24579737
TI  - Aging and cancer vaccines.
AB  - Cancer vaccination is less effective at old than at young age, due to T cell
      unresponsiveness. This is caused by age-related changes of the immune system.
      Major immune defects at older age are lack of naive T cells, impaired activation
      pathways of T cells and antigen-presenting cells (APC), and age-related changes
      in the tumor microenvironment (TME). Also innate immune responses are affected by
      aging, but this seems less abundant than adaptive immune responses. In this
      review we compared various cancer vaccine studies at young and old age,
      demonstrating the importance of both innate and adaptive immune responses for
      cancer immunotherapy. Moreover, we found suggestive evidence that innate immune
      responses could help improve adaptive immune responses through cancer vaccination
      in old age. 

PMID- 24579739
TI  - A PCR marker linked to a THCA synthase polymorphism is a reliable tool to
      discriminate potentially THC-rich plants of Cannabis sativa L.
AB  - Neither absolute THC content nor morphology allows the unequivocal discrimination
      of fiber cultivars and drug strains of Cannabis sativa L. unequivocally. However,
      the CBD/THC ratio remains constant throughout the plant's life cycle, is
      independent of environmental factors, and considered to be controlled by a single
      locus (B) with two codominant alleles (B(T) and B(D)). The homozygous B(T)/B(T)
      genotype underlies the THC-predominant phenotype, B(D)/B(D) is CBD predominant,
      and an intermediate phenotype is induced by the heterozygous state (B(T)/B(D)).
      Using PCR-based markers in two segregating populations, we proved that the THCA
      synthase gene represents the postulated B locus and that specific sequence
      polymorphisms are absolutely linked either to the THC-predominant or the THC
      intermediate chemotype. The absolute linkage provides an excellent reliability of
      the marker signal in forensic casework. For validation, the species-specific
      marker system was applied to a large number of casework samples and fiber hemp
      cultivars.

PMID- 24579735
TI  - Aging, nutrient signaling, hematopoietic senescence, and cancer.
AB  - It is well known that cancer is one of the main causes of mortality in the aged
      population. Recent studies suggest that oncogenic pathways, such as the insulin
      like growth factor-1 (IGF-I), Ras, and Akt/PKB, can contribute to both aging and
      cancer not only by promoting growth and preventing apoptosis, but also by
      promoting DNA damage and genomic instability. Epidemiological studies suggest
      that the chronic, low-grade inflammation that accompanies aging also contributes
      to tissue damage and tumor progression. Coupled with the accumulation of
      senescent cells and declining immune function, this leads to the generation and
      survival of cancer cells, possibly explaining why advanced age is the primary
      risk factor for cancer. 

PMID- 24579740
TI  - Dynamics and a unified understanding of competitive [2,3]- and [1,2]-sigmatropic
      rearrangements based on a study of ammonium ylides.
AB  - The [2,3]- and [1,2]-sigmatropic rearrangements of ammonium ylides are studied by
      a combination of experimental, standard computational, and dynamic trajectory
      methods. The mixture of concerted [2,3] rearrangement and bond cleavage observed
      experimentally is accounted for by the outcome of trajectories passing through
      the formal [2,3] rearrangement transition state. In this way the bond cleavage is
      promoted by the pericyclic stabilization of the [2,3] transition state. It is
      proposed that this dynamic effect is responsible for the pervasive co-occurrence
      of the two rearrangements. 

PMID- 24579741
TI  - Appropriate implementation of echocardiography in Takotsubo syndrome: earlier and
      more frequently.

PMID- 24579743
TI  - Live/real time three-dimensional transesophageal echocardiographic assessment of
      ventricular septal volume and mass before and after myectomy in hypertrophic
      cardiomyopathy.
AB  - Hypertrophic cardiomyopathy (HCM) is the most common genetically transmitted
      cardiomyopathy. In patients resistant to medical management, myectomy is the
      surgical procedure of choice to reduce the symptoms of left ventricular outflow
      obstruction. Two-dimensional transesophageal echocardiography (2DTEE) has become
      part of the operative procedure by decreasing the incidence of postoperative
      complications. However, because of the three-dimensional geometry of left
      ventricular outflow tract, it is unable to comprehensively assess the location
      and severity of the obstruction and to provide accurate guidance during myectomy.
      In this study, 10 patients with HCM underwent live/real time three-dimensional
      transesophageal echocardiography (3DTEE) intra-operatively to measure the volume
      of the resected septum. This volume correlated well with the volume of the
      resected septal muscle directly obtained using a graduating cylinder containing
      water (r = 0.9, P < 0.000). 3DTEE may be potentially used as an adjunct to guide
      the surgeon in performing an adequate myectomy with a lower incidence of residual
      obstruction and complications such as an iatrogenic ventricular septal defect. 

PMID- 24579746
TI  - Parasitic diseases in travelers: a focus on therapy.
AB  - Parasitic infections are an important cause of illness among returned travelers,
      and can lead to considerable morbidity and, in some cases, mortality. The
      complexity of parasitic life cycles and geographic specificities can present
      diagnostic challenges, particularly in non-endemic settings to which most
      travelers return for care. Clinical manifestations reflect the diverse taxonomy
      and pathogenesis of parasites, and appropriate diagnosis and management therefore
      necessitate a high index of suspicion of parasitic illnesses. Much of our
      knowledge surrounding management of parasitic infections in travelers is
      extrapolated from evidence derived in endemic populations, or is based on expert
      opinion and case series. We herein provide an overview of parasitic diseases of
      short-term travelers, and summarize current therapeutic strategies for each
      illness. 

PMID- 24579747
TI  - New treatment approaches in chronic kidney disease-associated anaemia.
AB  - INTRODUCTION: Erythropoiesis-stimulating agents (ESA) and iron are the main tools
      for treating anaemia associated with chronic kidney disease (CKD). Pharmaceutical
      research has focused on modified epoetins or different strategies to stimulate
      erythropoiesis with the idea of improving relative disadvantages of the molecules
      already available in the market. AREAS COVERED: Following a literature search on
      PubMed using anaemia, haemoglobin, erythropoietin (EPO), hypoxia-inducible
      transcription factor (HIF) inhibitors and chronic kidney disease as keywords, we
      critically analysed new strategies for increasing erythropoiesis, looking in
      depth at their peculiar characteristics and possible advantages in the clinical
      setting. EXPERT OPINION: In recent years the ESA market is facing a number of
      hurdles making it less appealing than before. Economic recession or stagnation
      has raised the need of sustainability of medical treatment. New treatments must
      bring clear benefits compared to existing drugs. In addition to this, ESA
      consumption has been progressively reduced, fearing possible risks of increased
      cardiovascular events especially when given at excessive doses. New drugs may
      also undergo premature stopping because of unexpected adverse reactions as for
      peginesatide. At present, the most promising approach to anaemia treatment in CKD
      patients is the manipulation of the HIF system. The regulation of activin A
      pathway is another option with good potential, also considering the additional
      advantage of increasing bone mass.

PMID- 24579748
TI  - Treatment of idiopathic intracranial hypertension with gastric bypass surgery.
AB  - Idiopathic intracranial hypertension (IIH) is defined by elevated intracranial
      pressure and associated headaches, changes in vision and pulsatile tinnitus,
      among other symptoms. It occurs most frequently in young, obese women. Gastric
      bypass surgery has been used to treat morbid obesity and its comorbidities, and
      IIH has recently been considered among these indications. We present a case
      report of a 29-year-old female with a maximum BMI of 50.3 and a 5-year history of
      severe headaches and moderate papilledema due to IIH. She also developed migraine
      headaches. After a waxing and waning course and various medical treatments, the
      patient underwent laparoscopic Roux-en-Y gastric bypass surgery with anterior
      repair of hiatal hernia. Dramatic improvement in IIH headaches occurred by 4
      months postprocedure and was maintained at 1 year, when she reached her weight
      plateau with a BMI of 35. Presurgery migraines persisted. This adds to the small
      number of case reports and retrospective analyses of the successful treatment of
      IIH with gastric bypass surgery, and brings this data from the surgical
      literature into the neurological domain. It offers insight into an early time
      course for symptom resolution, and explores the impact of weight-loss surgery on
      migraine headaches. This treatment modality should be further investigated
      prospectively to analyze the rate of headache improvement with weight loss, the
      amount of weight loss needed for clinical improvement, and the possible
      correlation with improvement in papilledema. 

PMID- 24579749
TI  - Evaluation of a smoke-free law on indoor air quality and on workers' health in
      Portuguese restaurants.
AB  - Workplace bans on smoking are interventions to reduce exposure to secondhand
      smoke (SHS) to try to prevent harmful health effects. The Portuguese Government
      on January 1, 2008, introduced the first national law banning smoking in public
      workplaces, including restaurants. The main aim of this study was to examine the
      impact of this law on indoor air quality (IAQ) in restaurants and on the
      respiratory and sensory health of restaurant workers. Concentrations of
      respirable suspended particulate matter (RSP), total volatile organic compounds
      (TVOC), carbon monoxide (CO), and carbon dioxide (CO2) in 10 restaurants were
      measured and compared before and after the ban. Benzene (C6H6) concentrations
      were also measured in all restaurants. Fifty-two and twenty-eight restaurant
      workers, respectively, answered questionnaires on exposure to SHS, and
      respiratory and sensory symptoms in the pre- and post-ban phases. There was a
      statistically significant decrease in RSP, CO, TVOC, and C6H6 concentrations
      after the ban. Additionally, in both phases the monitored CO2 concentrations
      greatly exceeded 1800 mg x m(-3), suggesting inefficient ventilation of the
      indoor spaces. Between pre- and post-ban phases a significant reduction in self
      reported workplace SHS exposure was also observed after the enforcement of the
      law, as well as a significant marked reduction in dry, itching, irritated, or
      watery eyes, nasal problems, sore or dry throat, cough, wheeze, and headache.
      This study provides, in a single investigation, comparison of IAQ and respiratory
      health in Portugal before and after the introduction of the smoke-free law, the
      first data reported in the literature to our knowledge. Our findings suggest that
      a total workplace smoking ban results in a significant reduction in indoor air
      pollution and an improvement in the respiratory health of restaurant workers.
      These observations may have implications for policymakers and legislators
      currently considering the nature and extent of their smoke-free workplace
      legislation and could provide a useful contribution to the implementation of
      public health prevention programs.

PMID- 24579750
TI  - Blood manganese as an exposure biomarker: state of the evidence.
AB  - Despite evidence of adverse health effects resulting from exposure to manganese
      (Mn), biomarkers of exposure are poorly understood. To enhance understanding,
      mean blood Mn (MnB) and mean air Mn (MnA) were extracted from 63 exposure groups
      in 24 published papers, and the relationship was modeled using segmented
      regression. On a log/log scale, a positive association between MnA and MnB was
      observed among studies reporting MnA concentrations above about 10 MUg/m(3),
      although interpretation is limited by largely cross-sectional data, study design
      variability, and differences in exposure monitoring methods. Based on the results
      of the segmented regression, we hypothesize that below the concentration of about
      10 MUg/m(3), Mn in the body is dominated by dietary Mn, and additional inhaled Mn
      only causes negligible changes in Mn levels unless the inhaled amount is
      substantial. However, stronger study designs are required to account for temporal
      characteristics of the MnA to MnB relationships that reflect the underlying
      physiology and toxicokinetics of Mn uptake and distribution. Thus, we present an
      inception cohort study design we have conducted among apprentice welders, and the
      analytical strengths this study design offers. To determine if blood could be a
      useful biomarker for Mn to be utilized by industrial hygienists in general
      industry requires additional time-specific analyses, which our inception cohort
      study design will allow. 

PMID- 24579753
TI  - Improving flow patterns and spillage characteristics of a box-type commercial
      kitchen hood.
AB  - A conventional box-type commercial kitchen hood and its improved version (termed
      the "IQV commercial kitchen hood") were studied using the laser-assisted smoke
      flow visualization technique and tracer-gas (sulfur hexafluoride) detection
      methods. The laser-assisted smoke flow visualization technique qualitatively
      revealed the flow field of the hood and the areas apt for leakages of hood
      containment. The tracer-gas concentration detection method measured the
      quantitative leakage levels of the hood containment. The oil mists that were
      generated in the conventional box-type commercial kitchen hood leaked
      significantly into the environment from the areas near the front edges of ceiling
      and side walls. Around these areas, the boundary-layer separation occurred,
      inducing highly unsteady and turbulent recirculating flow, and leading to
      spillages of hood containment due to inappropriate aerodynamic design at the
      front edges of the ceiling and side walls. The tracer-gas concentration
      measurements on the conventional box-type commercial kitchen hood showed that the
      sulfur hexafluoride concentrations detected at the hood face attained very large
      values on an order of magnitude about 10(3)-10(4) ppb. By combining the backward
      offset narrow suction slot, deflection plates, and quarter-circular arcs at the
      hood entrance, the IQV commercial kitchen hood presented a flow field containing
      four backward-inclined cyclone flow structures. The oil mists generated by
      cooking were coherently confined in these upward-rising cyclone flow structures
      and finally exhausted through the narrow suction slot. The tracer-gas
      concentration measurements on the IQV commercial kitchen hood showed that the
      order of magnitude of the sulfur hexafluoride concentrations detected at the hood
      face is negligibly small--only about 10(0) ppb across the whole hood face.

PMID- 24579752
TI  - A novel algorithm for determining contact area between a respirator and a
      headform.
AB  - The contact area, as well as the contact pressure, is created when a respiratory
      protection device (a respirator or surgical mask) contacts a human face. A
      computer-based algorithm for determining the contact area between a headform and
      N95 filtering facepiece respirator (FFR) was proposed. Six N95 FFRs were applied
      to five sizes of standard headforms (large, medium, small, long/narrow, and
      short/wide) to simulate respirator donning. After the contact simulation between
      a headform and an N95 FFR was conducted, a contact area was determined by
      extracting the intersection surfaces of the headform and the N95 FFR. Using
      computer-aided design tools, a superimposed contact area and an average contact
      area, which are non-uniform rational basis spline (NURBS) surfaces, were
      developed for each headform. Experiments that directly measured dimensions of the
      contact areas between headform prototypes and N95 FFRs were used to validate the
      simulation results. Headform sizes influenced all contact area dimensions (P <
      0.0001), and N95 FFR sizing systems influenced all contact area dimensions (P <
      0.05) except the left and right chin regions. The medium headform produced the
      largest contact area, while the large and small headforms produced the smallest. 

PMID- 24579751
TI  - Criteria for the collection of useful respirator performance data in the
      workplace.
AB  - Workplace protection factors (WPFs) are intended to measure the ability of a
      respiratory protective device (RPD) to reduce contaminant exposure when used in
      the context of an effective respiratory protection program. In 1992, members of
      the American Industrial Hygiene Association Respiratory Protection Committee
      (RPC) published a review of important issues and considerations for measuring
      respirator performance in the workplace. The RPC recognized that respirator
      testing in workplaces can have a variety of objectives and endpoints, and that
      not all workplace measurements are WPFs. That paper addressed concerns in the
      general categories of 1) study objectives; 2) site selection; 3) subject
      selection and preparation; 4) sampling and analytical methods; and 5) data
      analysis. No specific protocol for measuring WPFs was recommended by the RPC, and
      attempts to reach a U.S. consensus on a WPF protocol since 1992 have not
      succeeded. Numerous studies have implemented the principles for WPF measurement
      described in the RPC paper. Modifications to the original recommendations have
      been made to reflect the current state of the art. This article describes what
      has been learned in recent years in each of the five categories identified in the
      1992 discussion. Because of the wide variety of workplaces and work activities,
      contaminants and respiratory protective devices, a strict protocol is not
      appropriate for collecting WPF data. Rather, the minimum requirements for the
      collection and presentation of meaningful respirator performance data in the
      workplace are described. Understanding of these principles will permit useful RPD
      performance data to be generated. 

PMID- 24579754
TI  - Methamphetamine residue dermal transfer efficiencies from household surfaces.
AB  - Methamphetamine contamination from illegal production operations poses a
      potential health concern for emergency responders, child protective services, law
      enforcement, and children living in contaminated structures. The objective of
      this study was to evaluate dermal transfer efficiencies of methamphetamine from
      contaminated household surfaces. These transfer efficiencies are lacking for
      methamphetamine, and would be beneficial for use in exposure models. Surfaces
      were contaminated using a simulated smoking method in a stainless steel chamber.
      Household surfaces were carpet, painted drywall, and linoleum. Dermal transfer
      efficiencies were obtained using cotton gloves for two hand conditions, dry or
      saliva moistened (wet). In addition, three contact scenarios were evaluated for
      both hand conditions: one, two, or three contacts with contaminated surfaces.
      Dermal transfer efficiencies were calculated for both hand conditions and used as
      inputs in a Stochastic Human Exposure and Dose Simulation model (SHEDS
      Multimedia, Office of Research and Development, United States Environmental
      Protection Agency, Research Triangle Park, N.C.). Results of this study showed
      that average dermal transfer efficiencies of methamphetamine ranged from 11% for
      dry hands to 26% for wet hands. There was a significantly higher wet transfer as
      compared to dry transfer for all surfaces. For wet hands, dermal transfer
      depended on surface type with higher transfer from carpet and linoleum as
      compared to drywall. Based on our estimates of dermal transfer efficiency, a
      surface contamination clearance level of 1.5 MUg/100 cm(2) may not ensure
      absorbed doses remain below the level associated with adverse health effects in
      all cases. Additional dermal transfer studies should be performed using skin
      surrogates that may better predict actual skin transfer. 

PMID- 24579755
TI  - Evaluation of protective ensemble thermal characteristics through sweating hot
      plate, sweating thermal manikin, and human tests.
AB  - The purpose of this study was to evaluate the predictive capability of fabric
      Total Heat Loss (THL) values on thermal stress that Personal Protective Equipment
      (PPE) ensemble wearers may encounter while performing work. A series of three
      tests, consisting of the Sweating Hot Plate (SHP) test on two sample fabrics and
      the Sweating Thermal Manikin (STM) and human performance tests on two single
      layer encapsulating ensembles (fabric/ensemble A = low THL and B = high THL), was
      conducted to compare THL values between SHP and STM methods along with human
      thermophysiological responses to wearing the ensembles. In human testing, ten
      male subjects performed a treadmill exercise at 4.8 km and 3% incline for 60 min
      in two environmental conditions (mild = 22 degrees C, 50% relative humidity (RH)
      and hot/humid = 35 degrees C, 65% RH). The thermal and evaporative resistances
      were significantly higher on a fabric level as measured in the SHP test than on
      the ensemble level as measured in the STM test. Consequently the THL values were
      also significantly different for both fabric types (SHP vs. STM: 191.3 vs. 81.5
      W/m(2) in fabric/ensemble A, and 909.3 vs. 149.9 W/m(2) in fabric/ensemble B (p <
      0.001). Body temperature and heart rate response between ensembles A and B were
      consistently different in both environmental conditions (p < 0.001), which is
      attributed to significantly higher sweat evaporation in ensemble B than in A (p <
      0.05), despite a greater sweat production in ensemble A (p < 0.001) in both
      environmental conditions. Further, elevation of microclimate temperature (p <
      0.001) and humidity (p < 0.01) was significantly greater in ensemble A than in B.
      It was concluded that: (1) SHP test determined THL values are significantly
      different from the actual THL potential of the PPE ensemble tested on STM, (2)
      physiological benefits from wearing a more breathable PPE ensemble may not be
      feasible with incremental THL values (SHP test) less than approximately 150-200
      W.m(2), and (3) the effects of thermal environments on a level of heat stress in
      PPE ensemble wearers are greater than ensemble thermal characteristics. 

PMID- 24579757
TI  - A comparison between different fouling-release elastomer coatings containing
      surface-active polymers.
AB  - Surface-active polymers derived from styrene monomers containing siloxane (S),
      fluoroalkyl (F) and/or ethoxylated (E) side chains were blended with an elastomer
      matrix, either poly(dimethyl siloxane) (PDMS) or poly(styrene-b-(ethylene-co
      butylene)-b-styrene) (SEBS), and spray-coated on top of PDMS or SEBS preformed
      films. By contact angle and X-ray photoelectron spectroscopy measurements, it was
      found that the surface-active polymer preferentially populated the outermost
      layers of the coating, despite its low content in the blend. However, the self
      segregation process and the response to the external environment strongly
      depended on both the chemistry of the polymer and the type of matrix used for the
      blend. Additionally, mechanical testing showed that the elastic modulus of SEBS
      based coatings was one order of magnitude higher than that of the corresponding
      PDMS-based coatings. The coatings were subjected to laboratory bioassays with the
      marine alga Ulva linza. PDMS-based coatings had superior fouling-release
      properties compared to the SEBS-based coatings.

PMID- 24579758
TI  - Examination of the hierarchical structure of the brief COPE in a French sample:
      empirical and theoretical convergences.
AB  - This study aimed to determine whether the various factors of coping as measured
      by the Brief COPE could be integrated into a more parsimonious hierarchical
      structure. To identify a higher structure for the Brief COPE, several measurement
      models based on prior theoretical and hierarchical conceptions of coping were
      tested. First, confirmatory factor analysis (CFA) results revealed that the Brief
      COPE's 14 original factors could be represented more parsimoniously with 5 higher
      order dimensions: problem-solving, support-seeking, avoidance, cognitive
      restructuring, and distraction (N = 2,187). Measurement invariance across gender
      was also shown. Second, results provided strong support for the cross-validation
      and the concurrent validity of the hierarchical structure of the Brief COPE (N =
      584). Results indicated statistically significant correlations between Brief COPE
      factors and trait anxiety and perceived stress. Limitations and theoretical and
      methodological implications of these results are discussed. 

PMID- 24579759
TI  - Inelastic neutron scattering studies of methyl chloride synthesis over alumina.
AB  - Not only is alumina the most widely used catalyst support material in the world,
      it is also an important catalyst in its own right. One major chemical process
      that uses alumina in this respect is the industrial production of methyl
      chloride. This is a large scale process (650,000 metric tons in 2010 in the
      United States), and a key feedstock in the production of silicones that are
      widely used as household sealants. In this Account, we show how, in partnership
      with conventional spectroscopic and reaction testing methods, inelastic neutron
      scattering (INS) spectroscopy can provide additional insight into the active
      sites present on the catalyst, as well as the intermediates present on the
      catalyst surface. INS spectroscopy is a form of vibrational spectroscopy, where
      the spectral features are dominated by modes involving hydrogen. Because of this,
      most materials including alumina are largely transparent to neutrons.
      Advantageously, in this technique, the entire "mid-infrared", 0-4000 cm(-1),
      range is accessible; there is no cut-off at ~1400 cm(-1) as in infrared
      spectroscopy. It is also straightforward to distinguish fundamental modes from
      overtones and combinations. A key parameter in the catalyst's activity is the
      surface acidity. In infrared spectroscopy of adsorbed pyridine, the shifts in the
      ring stretching modes are dependent on the strength of the acid site. However,
      there is a very limited spectral range available. We discuss how we can observe
      the low energy ring deformation modes of adsorbed pyridine by INS spectroscopy.
      These modes can undergo shifts that are as large as those seen with infrared
      inspectroscopy, potentially enabling finer discrimination between acid sites.
      Surface hydroxyls play a key role in alumina catalysis, but in infrared
      spectroscopy, the presence of electrical anharmonicity complicates the
      interpretation of the O-H stretch region. In addition, the deformations lie below
      the infrared cut-off. Both of these limitations are irrelevant to INS
      spectroscopy, and all the modes are readily observable. When we add HCl to the
      catalyst surface, the acid causes changes in the spectra. We can then deduce both
      that the surface chlorination leads to enhanced Lewis acidity and that the
      hydroxyl group must be threefold coordinated. When we react eta-alumina with
      methanol, the catalyst forms a chemisorbed methoxy species. Infrared spectroscopy
      clearly shows its presence but also indicates the possible coexistence of a
      second species. Because of INS spectroscopy's ability to discriminate between
      fundamental modes and combinations, we were able to unambiguously show that there
      is a single intermediate present on the surface of the active catalyst. This work
      represents a clear example where an understanding of the chemistry at the
      molecular level can help rationalize improvements in a large scale industrial
      process with both financial and environmental benefits.

PMID- 24579760
TI  - Intolerance of uncertainty mediates the relation between generalized anxiety
      disorder symptoms and anger.
AB  - Previous research has shown that individuals with generalized anxiety disorder
      (GAD) report elevated anger compared with nonanxious individuals; however, the
      pathways linking GAD and anger are currently unknown. We hypothesized that
      negative beliefs about uncertainty, negative beliefs about worry and
      perfectionism dimensions mediate the relationship between GAD symptoms and anger
      variables. We employed multiple mediation with bootstrapping on cross-sectional
      data from a student sample (N = 233) to test four models assessing potential
      mediators of the association of GAD symptoms to inward anger expression, outward
      anger expression, trait anger and hostility, respectively. The belief that
      uncertainty has negative personal and behavioural implications uniquely mediated
      the association of GAD symptoms to inward anger expression (confidence interval
      [CI] = .0034, .1845, PM = .5444), and the belief that uncertainty is unfair and
      spoils everything uniquely mediated the association of GAD symptoms to outward
      anger expression (CI = .0052, .1936, PM = .4861) and hostility (CI = .0269,
      .2427, PM = .3487). Neither negative beliefs about worry nor perfectionism
      dimensions uniquely mediated the relation of GAD symptoms to anger constructs. We
      conclude that intolerance of uncertainty may help to explain the positive
      connection between GAD symptoms and anger, and these findings give impetus to
      future longitudinal investigations of the role of anger in GAD.

PMID- 24579761
TI  - A survey: how periodontists and other dental professionals view the scope of
      periodontics.
AB  - BACKGROUND: How do periodontists think of themselves when they define their
      practices? How do other dental professionals view the scope of the specialty of
      periodontology? A strong component of periodontal residency programs is
      extracting teeth and preserving or building bony ridges for the eventual
      placement of implants. Has the discipline of periodontology moved away from
      retaining and treating the natural dentition? By the use of a rank-order survey,
      the practice of periodontology was defined by periodontists and other dental
      professionals. METHODS: In a pilot study, respondents were asked to list the
      answers to the question, "What is a periodontist?" The results were consolidated
      into eight statements. The eight statements were placed into an anonymous rank
      order survey, and more than 1,200 responses were returned. The responses
      primarily came from periodontists, hygienists, general practitioners, dental
      students, and dental hygiene students. RESULTS: "Periodontists surgically treat
      advanced gum and bone infection problems" was considered the most important
      statement in all of the cohorts. The least important statement considered by all
      was, "Periodontists are educators promoting health." Non-periodontist dentists
      (NPDs) ranked the statement, "Periodontists perform dental implants and related
      procedures" less importantly (P <0.001) than the periodontists. The non
      periodontist cohort (NPC), which includes NPDs and dental hygienists, ranked the
      statement, "Periodontists' treatments help general dentists and other specialists
      increase successful therapeutic outcomes" as second most important. CONCLUSIONS:
      The results of this survey indicate that periodontists ranked the placement of
      implants and their related procedures higher than the NPC. NPDs appear to value
      periodontists in treating the natural dentition for their patients. The NPC
      appreciates that periodontal therapy done by periodontists increases their
      therapeutic success for their patients.

PMID- 24579762
TI  - Bacteria community study of combined periodontal-endodontic lesions using
      denaturing gradient gel electrophoresis and sequencing analysis.
AB  - BACKGROUND: The entire microbial population and predominant microflora of root
      canals (RCs) and adjacent periodontal pockets (PPs) from teeth with combined
      periodontal-endodontic lesions were determined and compared. METHODS: Pooled RC
      and PP samples were collected from the molars of 20 patients diagnosed with
      combined periodontal-endodontic lesions. DNA was extracted for polymerase chain
      reaction-based denaturing gradient gel electrophoresis (PCR-DGGE), cloning, and
      sequence analysis. A coefficient of similarity (Cs) was used to determine the
      similarity of the bacterial profiles from RCs and PPs. RESULTS: Significantly
      fewer bands were produced by PCR-DGGE from RCs (5.9 +/- 1.7) than from PPs (8.0
      +/- 1.8) (P <0.001). The average Cs of the RC and PP samples was 93.81% +/-
      10.26%. Overall, 60 genera/species were identified by sequencing. Of these, the
      predominant genera in RCs were Porphyromonas sp. (13.9%), Filifactor sp. (12.5%),
      and Parvimonas sp. (11.1%), similar to the genera obtained from PP samples. In
      total, 43 genera/species were common to the RC and PP samples. The most prevalent
      bacteria in both the RC and PP samples were (in descending order) Filifactor
      alocis, Parvimonas micra, Porphyromonas gingivalis, and Tannerella forsythia.
      CONCLUSIONS: The high similarity in the sets of organisms present in both RC and
      PP samples in this study suggests that the pocket could be a source of RC
      infection. The data also demonstrate that combined periodontal-endodontic lesions
      consist of a diverse and complex microbial community.

PMID- 24579763
TI  - Commentary: Oral bacteria as drivers for colorectal cancer.

PMID- 24579764
TI  - Irradiation by gallium-aluminum-arsenate diode laser enhances the induction of
      nitric oxide by Porphyromonas gingivalis in RAW 264.7 cells.
AB  - BACKGROUND: Low-level laser irradiation promotes cell viability and wound healing
      in periodontal tissue. However, its effect on periodontal pathogenic bacteria is
      unknown. The purpose of this study is to investigate the biologic effect of low
      level laser irradiation on Porphyromonas gingivalis. METHODS: A murine macrophage
      cell line (RAW 264.7) was cultured and treated with gallium-aluminum-arsenate
      (GaAlAs) laser-irradiated P. gingivalis with varying levels of energy fluency.
      Gene expression of monocyte chemotactic protein-1 (MCP-1), interleukin-6 (IL-6),
      interferon-beta (IFN-beta), and inducible nitric oxide synthase (iNOS) was
      examined by reverse transcription-polymerase chain reaction. Production of iNOS
      was determined by Western blot analysis, and nitric oxide (NO) release was
      assessed using Griess reagent. Flow cytometric analysis was performed to
      determine the activation of Toll-like receptors (TLRs) in response to P.
      gingivalis. RESULTS: The laser-irradiated P. gingivalis significantly enhanced
      messenger RNA and protein levels of iNOS in RAW 264.7. Although the laser
      irradiation on P. gingivalis did not alter the expression level of MCP-1, IL-6,
      and IFN-beta, it showed a noticeable effect on NO production in RAW 264.7.
      Furthermore, the laser-irradiated P. gingivalis accelerated TLR2 activation, but
      not TLR4 activation. CONCLUSIONS: This study reveals that GaAlAs laser
      irradiation on P. gingivalis induced iNOS expression at the transcriptional and
      translation levels and increased NO release in macrophages. Moreover, it is
      confirmed that this process was mediated specifically by TLR2 activation. These
      findings suggest that low-level laser irradiation to periodontal pathogenic
      bacteria could be detrimental to periodontal treatments.

PMID- 24579765
TI  - Characterization of highly osteoblast/cementoblast cell clones from a CD105
      enriched periodontal ligament progenitor cell population.
AB  - BACKGROUND: It is known that periodontal ligament (PDL) harbors a heterogeneous
      progenitor cell population at different stages of lineage commitment. However,
      characterization of PDL stem cells committed to osteoblast/cementoblast (O/C)
      differentiation remains to be elucidated. The present study is carried out to
      isolate single cell-derived, cluster of differentiation (CD)105-positive PDL
      clones and to characterize the clones that present high potential to
      differentiate toward O/C phenotype in vitro. METHODS: Isolation of single cell
      derived colonies (clones) from a CD105-enriched PDL progenitor cell population
      was performed by the ring-cloning technique. Cell clones were evaluated for their
      O/C differentiation potential, metabolic activity, and expression of STRO-1
      protein. Additionally, the clones that showed potential to O/C differentiation
      were characterized by quantitative reverse-transcription polymerase chain
      reaction (qRT-PCR) for expression of runt-related transcriptor factor 2 (RUNX2),
      alkaline phosphatase, CD105, and CD166 during osteogenic induction. RESULTS: Six
      PDL-CD105(+) clones were obtained, three being highly O/C clones (C-O) and three
      others that did not have the ability to produce mineralized matrix in vitro (C
      F). The C-O group showed lower metabolic activity compared with the C-F group,
      and both cell groups were positively immunostained for STRO-1. qRT-PCR analysis
      demonstrated an increased expression of transcripts for RUNX2 and CD166 during
      the maturation of C-O cells toward O/C phenotype. CONCLUSIONS: These results
      provide evidence that PDL-CD105(+) purified progenitor cells comprise a
      heterogeneous cell population that presents a cell subset with high O/C potential
      and, further, that surface antigen CD166 is modulated during the O/C maturation
      of this cell subset.

PMID- 24579767
TI  - Current nanotechnological strategies for effective delivery of bioactive drug
      molecules in the treatment of tuberculosis.
AB  - Tuberculosis (TB) has gone from being a forgotten disease to a modern and
      recrudescent pathology from past decades. Some clinical problems and challenges
      associated with conventional TB chemotherapy include poor patient compliance,
      longer duration of chemotherapy, lesser cell permeability, primary drug
      resistance, difficulty in maintaining higher drug concentrations at the infected
      site, and degradation of the drug before reaching the target site. Thus, newer
      drug delivery approaches involving micrometric or nanometric carriers are needed.
      These delivery systems should provide advantages over conventional systems by
      producing optimum effectiveness to the target site, enhanced therapeutic
      efficacy, uniform distribution of the drug throughout the target site, increased
      bioavailability and sustainability of the drug, fewer side effects, and increased
      patient compliance. This article reviews recent updates and fabrication of drug
      delivery approaches for tuberculosis chemotherapy involving vesicular drug
      delivery systems (liposomes, niosomes, solid lipid nanoparticles), particulate
      drug delivery systems (nanoparticles, microparticles, dendrimers), supramolecular
      drug delivery systems (polymeric micelles), specialized drug delivery systems
      (nanosuspensions, nanoemulsions, microemulsions, dry powders), complex conjugate
      drug delivery systems (ISCOMs, cyclodextrin inclusion complexes), and other
      carrier-based drug delivery systems in order to improve patient outcomes. 

PMID- 24579766
TI  - Tiny technology proves big: a challenge at engineering, medicine and
      pharmaceutical sciences interface.
AB  - Nanoscale materials with a broad spectrum of applications are providing a new
      foundation for technological integration and innovation. In this article, we
      review various polymers being used, their polymeric properties, nanoparticle (NP)
      fabrication, and mechanisms and kinetics of drug release. Specific information is
      given on each polymer regarding transportation, fate, and delivery issues.
      Nanoparticles have been developed to deliver conventional drug molecules,
      peptides and proteins, vaccines, and genes or nucleotides. Nanoparticles have
      wide application in fields such as cancer therapeutics and targeted drug
      delivery, including transbarrier brain delivery, dermal and transdermal delivery,
      intraocular delivery, parenteral delivery, and imaging and diagnostics. In this
      review, we focus on the potentials of nanotechnology in medicine, and we discuss
      different nanoparticulate drug delivery systems, including polymeric NPs, metal
      and metal oxide NPs, ceramics, quantum dots, carbon nanotubes, polymeric
      micelles, and dendrimers along with their applications in therapeutics, imaging,
      and diagnostics. In addition, we identify several interesting developments that
      will affect the future of nanotechnology and nanomedicine. 

PMID- 24579768
TI  - Induced tolerance from a sublethal insecticide leads to cross-tolerance to other
      insecticides.
AB  - As global pesticide use increases, the ability to rapidly respond to pesticides
      by increasing tolerance has important implications for the persistence of
      nontarget organisms. A recent study of larval amphibians discovered that
      increased tolerance can be induced by an early exposure to low concentrations of
      a pesticide. Since natural systems are often exposed to a variety of pesticides
      that vary in mode of action, we need to know whether the induction of increased
      tolerance to one pesticide confers increased tolerance to other pesticides. Using
      larval wood frogs (Lithobates sylvaticus), we investigated whether induction of
      increased tolerance to the insecticide carbaryl (AChE-inhibitor) can induce
      increased tolerance to other insecticides that have the same mode of action
      (chlorpyrifos, malathion) or a different mode of action (Na(+)channel-interfering
      insecticides; permethrin, cypermethrin). We found that embryonic exposure to
      sublethal concentrations of carbaryl induced higher tolerance to carbaryl and
      increased cross-tolerance to malathion and cypermethrin but not to chlorpyrifos
      or permethrin. In one case, the embryonic exposure to carbaryl induced tolerance
      in a nonlinear pattern (hormesis). These results demonstrate that that the newly
      discovered phenomenon of induced tolerance also provides induced cross-tolerance
      that is not restricted to pesticides with the same mode of action. 

PMID- 24579770
TI  - Structural integrity of medial temporal lobes of patients with acute mild
      traumatic brain injury.
AB  - Post-traumatic amnesia (PTA) is an acute characteristic of traumatic brain injury
      (TBI) and the duration of PTA is commonly used to estimate the severity of brain
      injury. In the context of mild traumatic brain injury (MTBI), PTA is an essential
      part of the routine clinical assessment. Macroscopic lesions in temporal lobes,
      especially hippocampal regions, are thought to be connected to memory loss.
      However, conventional neuroimaging has failed to reveal neuropathological
      correlates of PTA in MTBI. Texture analysis (TA) is an image analysis technique
      that quantifies the minor MRI signal changes among image pixels and, therefore,
      the variations in intensity patterns within the image. The objective of this work
      was to apply the TA technique to MR images of MTBI patients and control subjects,
      and to assess the microstructural damage in medial temporal lobes of patients
      with MTBI with definite PTA. TA was performed for fluid-attenuated inversion
      recovery (FLAIR) images of 50 MTBI patients and 50 age- and gender-matched
      controls in the regions of the amygdala, hippocampus, and thalamus. It was
      hypothesized that 1) there would be statistically significant differences in TA
      parameters between patients with MTBIs and controls, and 2) the duration of PTA
      would be related to TA parameters in patients with MTBI. No significant textural
      differences were observed between patients and controls in the regions of
      interest (p>0.01). No textural features were observed to correlate with the
      duration of PTA. Subgroup analyses were conducted on patients with PTA of>1 h,
      (n=33) and compared the four TA parameters to the age- and gender-matched
      controls (n=33). The findings were similar. This study did not reveal significant
      textural changes in medial temporal structures that could be related to the
      duration of PTA.

PMID- 24579771
TI  - The clinical development of p53-reactivating drugs in sarcomas - charting future
      therapeutic approaches and understanding the clinical molecular toxicology of
      Nutlins.
AB  - INTRODUCTION: The majority of human sarcomas, particularly soft tissue sarcomas,
      are relatively resistant to traditional cytotoxic therapies. The proof-of-concept
      study by Ray-Coquard et al., using the Nutlin human double minute (HDM)2-binding
      antagonist RG7112, has recently opened a new chapter in the molecular targeting
      of human sarcomas. AREAS COVERED: In this review, the authors discuss the
      challenges and prospective remedies for minimizing the significant haematological
      toxicities of the cis-imidazole Nutlin HDM2-binding antagonists. Furthermore,
      they also chart the future direction of the development of p53-reactivating (p53
      RA) drugs in 12q13-15 amplicon sarcomas and as potential chemopreventative
      therapies against sarcomagenesis in germ line mutated TP53 carriers. Drawing
      lessons from the therapeutic use of Imatinib in gastrointestinal tumours, the
      authors predict the potential pitfalls, which may lie in ahead for the future
      clinical development of p53-RA agents, as well as discussing potential non
      invasive methods to identify the development of drug resistance. EXPERT OPINION:
      Medicinal chemistry strategies, based on structure-based drug design, are
      required to re-engineer cis-imidazoline Nutlin HDM2-binding antagonists into less
      haematologically toxic drugs. In silico modelling is also required to predict
      toxicities of other p53-RA drugs at a much earlier stage in drug development.
      Whether p53-RA drugs will be therapeutically effective as a monotherapy remains
      to be determined.

PMID- 24579769
TI  - Dynamic behavior of the active and inactive states of the adenosine A(2A)
      receptor.
AB  - The adenosine A2A receptor (A2AR) belongs to the superfamily of membrane proteins
      called the G-protein-coupled receptors (GPCRs) that form one of the largest
      superfamilies of drug targets. Deriving thermostable mutants has been one of the
      strategies used for crystallization of A2AR in both the agonist and antagonist
      bound conformational states. The crystal structures do not reveal differences in
      the activation mechanism of the mutant receptors compared to the wild type
      receptor, that have been observed experimentally. These differences stem from the
      dynamic behavior of the mutant receptors. Furthermore, it is not understood how
      the mutations confer thermostability. Since these details are difficult to obtain
      from experiments, we have used atomic level simulations to elucidate the dynamic
      behavior of the agonist and antagonist bound mutants as well the wild type A2AR.
      We found that significant enthalpic contribution leads to stabilization of both
      the inactive state (StaR2) and active-like state (GL31) thermostable mutants of
      A2AR. Stabilization resulting from mutations of bulky residues to alanine is due
      to the formation of interhelical hydrogen bonds and van der Waals packing that
      improves the transmembrane domain packing. The thermostable mutant GL31 shows
      less movement of the transmembrane helix TM6 with respect to TM3 than the wild
      type receptor. While restricted dynamics of GL31 is advantageous in its
      purification and crystallization, it could also be the reason why these mutants
      are not efficient in activating the G proteins. We observed that the calculated
      stress on each residue is higher in the wild type receptor compared to the
      thermostable mutants, and this stress is required for activation to occur. Thus,
      reduced dynamic behavior of the thermostable mutants leading to lowered
      activation of these receptors originates from reduced stress on each residue.
      Finally, accurate calculation of the change in free energy for single mutations
      shows good correlation with the change in the measured thermostability. These
      results provide insights into the effect of mutations that can be incorporated in
      deriving thermostable mutants for other GPCRs. 

PMID- 24579772
TI  - Developments in pediatric infectious diseases: a review of WSPID 2013.

PMID- 24579773
TI  - Ion coalescence of neutron encoded TMT 10-plex reporter ions.
AB  - Isobaric mass tag-based quantitative proteomics strategies such as iTRAQ and TMT
      utilize reporter ions in the low mass range of tandem MS spectra for relative
      quantification. The recent extension of TMT multiplexing to 10 conditions has
      been enabled by utilizing neutron encoded tags with reporter ion m/z differences
      of 6 mDa. The baseline resolution of these closely spaced tags is possible due to
      the high resolving power of current day mass spectrometers. In this work we
      evaluated the performance of the TMT10 isobaric mass tags on the Q Exactive
      Orbitrap mass spectrometers for the first time and demonstrated comparable
      quantification accuracy and precision to what can be achieved on the Orbitrap
      Elite mass spectrometers. However, we discovered, upon analysis of complex
      proteomics samples on the Q Exactive Orbitrap mass spectrometers, that the
      proximate TMT10 reporter ion pairs become prone to coalescence. The fusion of the
      different reporter ion signals into a single measurable entity has a detrimental
      effect on peptide and protein quantification. We established that the main reason
      for coalescence is the commonly accepted maximum ion target for MS2 spectra of
      1e6 on the Q Exactive instruments. The coalescence artifact was completely
      removed by lowering the maximum ion target for MS2 spectra from 1e6 to 2e5
      without any losses in identification depth or quantification quality of proteins.

PMID- 24579775
TI  - Glomerulopathy in adult recipients of pediatric kidneys.
AB  - To compare "for cause" renal biopsies (bx) from adult recipients of pediatric
      donor kidneys (PDK) versus adult-donor kidneys (ADKs), we reviewed 103 graft bx
      from 50 PDK recipients and 85 bx from 49 ADK recipients. PDK bx displayed more
      frequent glomerular pathology with immune complex-mediated glomerulonephritis
      present in 11/103 PDK versus 1/85 ADK (p < 0.05). In 15/103 PDK bx and 1/85 ADK
      (p = 0.001), the association of glomerular sclerosis, expanded mesangium, and
      halo of prominent podocytes by light microscopy, and ultrastructural glomerular
      basement membrane lamellation, configured a characteristic glomerulopathy.

PMID- 24579774
TI  - Evaluating state dependence and subtype selectivity of calcium channel modulators
      in automated electrophysiology assays.
AB  - Voltage-gated Ca2+ channels play essential roles in control of neurosecretion and
      muscle contraction. The pharmacological significance of Cav channels stem from
      their identification as the molecular targets of calcium blockers used in the
      treatment of cardiovascular diseases, such as hypertension, angina, and
      arrhythmia, and neurologic diseases, such as pain and seizure. It has been
      proposed that state-dependent Cav inhibitors, that is, those that preferentially
      bind to channels in open or inactivated states, may improve the therapeutic
      window over relatively state-independent Cav inhibitors. High-throughput
      fluorescent-based functional assays have been useful in screening chemical
      libraries to identify Cav inhibitors. However, hit confirmation, mechanism of
      action, and subtype selectivity are better suited to automated patch clamp assays
      that have sufficient capacity to handle the volume of compounds identified during
      screening, even of modest sized libraries (<=500,000 compounds), and the flexible
      voltage control that allows evaluation of state-dependent drug blocks. IonWorks
      Barracuda (IWB), the newest generation of IonWorks instruments, provides the
      opportunity to accelerate the Cav drug discovery studies in an automated patch
      clamp platform in 384-well format capable of medium throughput screening and
      profiling studies. We have validated hCav1.2, hCav2.1, hCav2.2, and hCav3.2
      channels assays on the IWB platform (population patch clamp mode) and
      demonstrated that the biophysical characteristics of the channels (activation,
      inactivation, and steady-state inactivation) obtained with the IWB system are
      consistent with known subtype-specific characteristics. Using standard reference
      compounds (nifedipine, BAY K8644, verapamil, mibefradil, and pimozide), we
      demonstrated subtype-selective and state- and use-dependent characteristics of
      drug-channel interactions. Here we describe the design and validation of novel
      robust high-throughput Cav channel assays on the IWB platform. The assays can be
      used to screen focused compound libraries for state-dependent Cav channel
      antagonists, to prioritize compounds for potency or to counterscreen for Cav
      subtype selectivity.

PMID- 24579777
TI  - A complete structural performance analysis and modelling of hydroxyapatite
      scaffolds with variable porosity.
AB  - The use of hydroxyapatite (HA) scaffolds for bone regeneration is an alternative
      procedure to treat bone defects due to cancer, other diseases or traumas.
      Although the use of HA has been widely studied in the literature, there are still
      some disparities regarding its mechanical performance. This paper presents a
      complete analysis of the structural performance of porous HA scaffolds based on
      experimental tests, numerical simulations and theoretical studies. HA scaffolds
      with variable porosity were considered and fabricated by the water-soluble
      polymer method, using poly vinyl alcohol as pore former. These scaffolds were
      then characterised by scanning electron microscopy, stereo microscopy, X-ray
      diffraction, porosity analysis and mechanical tests. Different scaffold models
      were proposed and analysed by the finite element method to obtain numerical
      predictions of the mechanical properties. Also theoretical predictions based on
      the (Gibson LJ, Ashby MF. 1988. Cellular solids: structure and properties.
      Oxford: Pergamon Press) model were obtained. Finally the experimental, numerical
      and theoretical results were compared. From this comparison, it was observed that
      the proposed numerical and theoretical models can be used to predict, with
      adequate accuracy, the mechanical performance of HA scaffolds for different
      porosity values.

PMID- 24579778
TI  - Resveratrol triggers protective autophagy through the ceramide/Akt/mTOR pathway
      in melanoma B16 cells.
AB  - Resveratrol (3,5,4'-trihydroxy-trans-stilbene, RSV), a natural polyphenolic
      compound, is known as a promising anti-cancer agent. In this study, we showed
      that RSV could inhibit the growth of B16 cells via induction of apoptosis.
      Moreover, our results showed for the first time that RSV induced autophagy in B16
      cells, which might occur through ceramide accumulation and Akt/mTOR pathway
      inhibition. Inhibition of autophagy by an autophagic inhibitor 3-methyladenine (3
      MA) or si-Beclin 1 enhanced RSV-induced cytotoxicity and apoptosis. Thus,
      autophagy inhibition represents a promising approach to improve the efficacy of
      RSV in the treatment of patients with melanoma. 

PMID- 24579779
TI  - Emotion appraisal and anxiety symptomatology in a university sample.
AB  - Current conceptualizations for anxiety disorders focus heavily on cognitive and
      behavioral aspects of anxiety and address other emotions to a far lesser extent.
      Studies have demonstrated that negative appraisals of anxiety and fear (e.g.,
      anxiety sensitivity) are elevated in each of the anxiety disorders and depressive
      disorders. Much less is known about how the appraisal of other emotions is
      related to anxiety disorder symptom presentation. The current study examines the
      appraisal of specific aversive emotions in relation to anxiety symptomatology.
      Undergraduate university students (N = 530) completed measures of specific
      anxiety and depressive symptoms, as well as a measure of emotional appraisal. A
      maximum likelihood estimated multivariate regression model was used to examine
      the unique relationships between emotional appraisal and anxiety and depressive
      symptoms. Results indicated that anxiety symptoms varied in their relationships
      with emotional appraisal. Each symptom group was highly related to fear of
      appraisals of anxiety; however, some anxiety symptoms were also related to fear
      of other emotional states, including guilt, sadness, disgust, lust, and
      embarrassment. Understanding the full range of appraisals of emotional
      experiences in anxiety conditions may help inform conceptualizations, and
      potentially treatments, by guiding the focus to the feared emotional states of
      the individual. The present study helps to clarify some of the relationships
      between emotion appraisal and anxiety symptoms.

PMID- 24579780
TI  - The long-term effects of sports concussion on retired Australian football
      players: a study using transcranial magnetic stimulation.
AB  - This study investigated corticomotor excitability and inhibition, cognitive
      functioning, and fine motor dexterity in retired elite and amateur Australian
      football (AF) players who had sustained concussions during their playing careers.
      Forty male AF players who played at the elite level (n=20; mean age 49.7+/-5.7
      years) or amateur level (n=20; mean age 48.4+/-6.9 years), and had sustained on
      average 3.2 concussions 21.9 years previously, were compared with 20 healthy age
      matched male controls (mean age 47.56+/-6.85 years). All participants completed
      assessments of fine dexterity, visuomotor reaction time, spatial working memory
      (SWM), and associative learning (AL). Transcranial magnetic stimulation (TMS) was
      used to measure corticospinal excitability: stimulus-response (SR) curves and
      motor evoked potential (MEP) 125% of active motor threshold (aMT); and
      intracortical inhibition: cortical silent period (cSP), short-interval
      intracortical inhibition (SICI), and long-interval intracortical inhibition
      (LICI). Healthy participants performed better in dexterity (p=0.003), reaction
      (p=0.003), and movement time (p=0.037) than did both AF groups. Differences
      between AF groups were found in AL (p=0.027) and SWM (p=0.024). TMS measures
      revealed that both AF groups showed reduced cSP duration at 125% aMT (p>0.001)
      and differences in SR curves (p>0.001) than did healthy controls. Similarly, SICI
      (p=0.012) and LICI (p=0.009) were reduced in both AF groups compared with
      controls. Regression analyses revealed a significant contribution to differences
      in motor outcomes with the three measures of intracortical inhibition. The
      measures of inhibition differed, however, in terms of which performance measure
      they had a significant and unique predictive relationship with, reflecting the
      variety of participant concussion injuries. This study is the first to
      demonstrate differences in motor control and intracortical inhibition in AF
      players who had sustained concussions during their playing career two decades
      previously.

PMID- 24579781
TI  - Activated hypoxia-inducible factor-1alpha pathway modulates early events in
      stretch-induced skin neovascularization via stromal cell-derived factor-1 and
      vascular endothelial growth factor.
AB  - BACKGROUND: Tissue expansion promotes skin regeneration. These responses occur
      only early after mechanical load and are then replaced by apoptosis-related
      events during stress relaxation. The mechanism modulating this transient process
      remains unknown. OBJECTIVE: To elucidate key phenomena that drive early
      regenerative events after tissue expansion. METHODS: Intraoperative tissue
      expansion was performed on 25 patients undergoing facial reconstruction. Paired
      skin biopsies were obtained from an expanded and unexpanded site from each
      patient. Differentially expressed genes were inspected by microarray and
      bioinformatic analysis, and dissected by quantitative polymerase chain reaction,
      Western blot and immunostaining. Paired biopsies from another nine patients
      undergoing cyclical expansion for 3 months were also investigated. RESULTS: A
      total of 124 upregulated and 282 downregulated genes were identified. Among them,
      the biological terms of extracellular matrix organization and blood vessel growth
      were most significantly enriched, as shown by Gene Ontology analysis. GeneMANIA
      dissection demonstrated an interactive network highlighted by the canonical
      hypoxia-inducible factor-1alpha (HIF-1alpha) pathway with stromal cell-derived
      factor-1 (SDF-1) and vascular endothelial growth factor (VEGFA) being the hub
      genes. Levels of the HIF-1alpha protein and its targets SDF-1 and VEGFA were
      elevated in expanded skin, and CD31 and Ki67 expression increased, indicating
      augmented vascularity and cell proliferation. Trafficking of CD34(+) CD133(+)
      endothelial progenitor cells was enhanced in skin undergoing long-time cyclical
      expansion, a phenomenon that was usually modulated by the HIF-1alpha pathway.
      CONCLUSIONS: The HIF-1alpha pathway is quickly activated and modulates early
      events in stretch-induced skin neovascularization. The effect may be augmented
      through enhanced endothelial progenitor cells recruitment into the expanded skin.

PMID- 24579782
TI  - Fermented Pu-erh tea increases in vitro anticancer activities in HT-29 cells and
      has antiangiogenetic effects on HUVECs.
AB  - Pu-erh tea is produced in China and known to possess medicinal properties. The
      anticancer and antiangiogenesis effects of fermented Pu-erh tea on HT-29 colon
      cancer cells and human umbilical vein endothelial cells, respectively, were
      examined. Two kinds of unfermented and fermented Pu-erh tea (Seven-son tea cake
      Pu-erh tea and Xiaguan bowl tea [X]) and green tea were used. An MTT assay showed
      fermented Pu-erh tea X (85% inhibition) possessed more potent anticancer
      activities than unfermented Pu-erh tea X (67% inhibition) and green tea (53%
      inhibition) (P < 0.05). Moreover, fermented Pu-erh tea X increased the number of
      apoptotic bodies determined through DAPI staining and flow cytometric analysis.
      Fermented Pu-erh tea X induced apoptosis indicated by increased expression of
      Bax, caspase-9, and caspase-3 messenger RNA and decreased expression of Bcl-2.
      Fermented Pu-erh tea X also had an anti-inflammation effect, shown in decreased
      expression of nuclear factor-kappaB-p65, inducible nitric oxide synthase, COX-2
      messenger RNA and increased expression of IkappaB-alpha. Further, fermented Pu
      erh teas showed stronger antiangiogenesis effects than the 2 other types of tea.
      After fermentation, the concentrations of gallic acid, resorcylic acid,
      quercetin, and kaempferol in Pu-erh tea were increased. These results
      collectively indicated that fermented and unfermented Pu-erh teas possess
      stronger anticancer and antiangiogenesis effects than green tea. Furthermore,
      fermented Pu-erh tea showed stronger functional activities than unfermented Pu
      erh tea. 

PMID- 24579783
TI  - The prognostic role of tumor-associated macrophages and dendritic cells in
      classic Hodgkin's lymphoma.
AB  - Tumor-associated macrophages (TAMs) and dendritic cells (DCs) may play a role in
      tumor progression as a part of the tumor microenvironment in many neoplasms,
      including those in Hodgkin's lymphoma. The current study investigated the
      relationship between the presence and density of macrophages and dendritic cells
      in the background of classic Hodgkin's lymphoma (CHL) and different
      clinicopathological parameters, including survival and response to therapy. CD68
      and CD1a immunohistochemical staining were used to detect and highlight
      macrophages and dendritic cells, respectively, in 61 cases of CHL. CD68 was
      expressed in all studied cases, with no significant association with the studied
      parameters. In total, 54.1% (33/61) of cases showed CD1a expression. High CD1a
      expression (>7%) was associated with localized lymphadenopathy (p=0.01), early
      stage (p=0.005), and good revised international prognostic index (R-IPI)
      (p=0.07). Hodgkin's lymphoma cases that showed high CD68 and low CD1a were
      associated with adverse prognostic parameters such as advanced stage (p=0.03) and
      generalized lymphadenopathy (p=0.05). Old age (>60 years) (P=0.005), poor R-IPI
      (P=0.010), and negative CD1a expression (P=0.045) were significantly associated
      with poor outcome. Finally, our study demonstrated the importance of the presence
      and density of DCs in determining progression and prognosis in CHL. A certain
      interaction between TAMs and DCs may affect the progression of CHL. Further
      investigation is required to clarify whether TAMs release certain factors that
      decrease the number or function of DCs. 

PMID- 24579785
TI  - Aqueous extract of pecan nut shell (Carya illinoensis [Wangenh.] K. Koch) exerts
      protection against oxidative damage induced by cyclophosphamide in rat testis.
AB  - This study investigated the protective effect of pecan nut (Carya illinoensis)
      shell aqueous extract (AE) on the oxidative and morphological status of rat
      testis treated with cyclophosphamide (CP). Wistar rats received water or AE (5%)
      ad libitum for 37 days. On day 30, half of each group received a single
      intraperitoneal administration of vehicle or CP 200 mg/kg. After 7 days, the
      animals were killed and their testis removed. Rats treated with CP presented
      reduced levels of lactate dehydrogenase, vitamin C, and gluthatione, as well as
      decreased catalase activity, increased lipid peroxidation levels and superoxide
      dismutase activity, no alteration in carbonyl protein levels, and a loss of
      morphological testicular integrity. In contrast, cotreatment with pecan shell AE
      totally prevented the decrease of lactate dehydrogenase and vitamin C levels and
      catalase activity and partially prevented the depletion of gluthatione levels.
      Moreover, it totally prevented the increase in superoxide dismutase activity and
      lipid peroxidation levels and maintained testicular integrity. These findings
      show the protective role of pecan shell AE in CP-induced testicular toxicity. The
      use of this phytotherapy may be considered to minimize deleterious effects
      related to this chemotherapy. 

PMID- 24579786
TI  - In silico analysis and validation of the proliferative potential of CLDN1
      expression in gastric cancer.
AB  - Tight junction protein claudin-1 (CLDN1) is mainly involved in the intercellular
      barrier function of epithelial cells and is known to be dysregulated in many
      cancer types, including gastrointestinal cancers. However, the mechanisms behind
      their potential involvement in the proliferation and survival of tumor cells
      remain unexplored. In this study we sought to investigate the potential role and
      possible regulators of CLDN1 in gastric cancer. By analyzing the gastric tumors
      from publicly available genome-wide messenger RNA expression profiles, CLDN1 was
      identified to be overexpressed in gastric tumors when compared with normal
      gastric tissues. Association between CLDN1 expression and clinical molecular
      subtype characteristics of gastric cancer showed an elevated CLDN1 expression
      pattern in intestinal and proliferative types of gastric cancer. Using in vitro
      CLDN1 perturbation analysis in gastric cancer cell lines, we confirmed the
      potential role of CLDN1 in cellular proliferation. Aided by the integrative
      analysis of the pathway prediction method with CLDN1 expression in gastric
      tumors, we demonstrated the negative association between estrogen-alpha and CLDN1
      expression in gastric tumors. Our results highlight the potential involvement of
      CLDN1 expression in gastric cancer. 

PMID- 24579787
TI  - Tyrosine kinase inhibitor AG490 inhibits the proliferation and migration and
      disrupts actin organization of cancer cells.
AB  - Metastasis, a multistep process, is a major cause of mortality in cancer
      patients. Thus, it is hoped that inhibition of metastasis at any step, such as
      proliferation, migration, or invasion, using small-molecule inhibitors will
      reduce this mortality. Recent study suggests that the Janus kinase/signal
      transducer and activator of transcription 3 signal transduction pathway is a
      central pathway that regulates tumor progression and metastasis and can be
      blocked using tyrosine kinase inhibitors. In this study we used a synthetic
      tyrosine kinase inhibitor, AG490, to block the constitutive activation of the
      Janus kinase/signal transducer and activator of transcription 3 pathway in A549
      lung carcinoma and A375 melanoma cell lines. Our results show that AG490 at
      subtoxic doses can effectively suppress tumor cell proliferation by limiting the
      expression of cyclin D1. Furthermore, AG490 is seen to induce apoptosis, inhibit
      cellular migration by disrupting actin organization, and suppress matrix
      metalloproteinase 2 activity. Taken together, these data demonstrate that AG490
      can exert antimetastatic activity by inhibiting cellular proliferation, invasion,
      and migration. 

PMID- 24579788
TI  - Nitrate shaped the selenate-reducing microbial community in a hydrogen-based
      biofilm reactor.
AB  - To study the effect of nitrate (NO3(-)) on selenate (SeO4(2-)) reduction, we
      tested a H2-based biofilm with a range of influent NO3(-) loadings. When SeO4(2-)
      was the only electron acceptor (stage 1), 40% of the influent SeO4(2-) was
      reduced to insoluble elemental selenium (Se(0)). SeO4(2-) reduction was
      dramatically inhibited when NO3(-) was added at a surface loading larger than
      1.14 g of N m(-2) day(-1), when H2 delivery became limiting and only 80% of the
      input NO3(-) was reduced (stage 2). In stage 3, when NO3(-) was again removed
      from the influent, SeO4(2-) reduction was re-established and increased to 60%
      conversion to Se(0). SeO4(2-) reduction remained stable at 60% in stages 4 and 5,
      when the NO3(-) surface loading was re-introduced at <= 0.53 g of N m(-2) day(
      1), allowing for complete NO3(-) reduction. The selenate-reducing microbial
      community was significantly reshaped by the high NO3(-) surface loading in stage
      2, and it remained stable through stages 3-5. In particular, the abundance of
      alpha-Proteobacteria decreased from 30% in stage 1 to less than 10% of total
      bacteria in stage 2. beta-Proteobacteria, which represented about 55% of total
      bacteria in the biofilm in stage 1, increased to more than 90% of phylotypes in
      stage 2. Hydrogenophaga, an autotrophic denitrifier, was positively correlated
      with NO3(-) flux. Thus, introducing a NO3(-) loading high enough to cause H2
      limitation and suppress SeO4(2-) reduction had a long-lasting effect on the
      microbial community structure, which was confirmed by principal coordinate
      analysis, although SeO4(2-) reduction remained intact.

PMID- 24579789
TI  - Effects of exogenous xylanase on performance, nutrient digestibility, volatile
      fatty acid production and digestive tract thermal profiles of broilers fed on
      wheat- or maize-based diet.
AB  - 1. A previous experiment reported that caecal temperature was negatively
      correlated with d 49 feed conversion ratio (FCR). This increased temperature in
      the caeca may indicate a prebiotic effect. An experiment was designed to
      investigate whether caecal temperature was affected in diets based on maize and
      whether other portions of the tract were affected. 2. A total of 25 Ross 308-d
      old male broilers were allocated to each of 8 replicate pens per treatment.
      Treatments followed a 2 * 3 factorial design: two diets based on wheat or maize
      and three levels of enzyme addition, 0, 16 000 or 32 000 BXU/kg. Growth
      performance was assessed between d 1 and 49. Digestibility measurements were
      taken at d 28 and 49. On d 49, the excised small and large intestine of each bird
      was thermally imaged, weighed and volatile fatty acids (VFA) measured. 3. On d 28
      and d 49, birds on the maize diets had higher feed intake and weight gain than
      those offered wheat diets. Additionally, on d 28, birds that received the maize
      diet had lower FCR than those offered the wheat diet. Enzyme improved FCR at d
      49, independently of cereal. On d 28, enzyme improved the coefficient of apparent
      ileal DM digestibility and the coefficient of apparent ileal nitrogen
      digestibility. Enzyme only improved apparent ileal digestible energy in wheat
      based diets (interactive term). On d 49, all digestibility parameters were
      improved by enzyme. Enzyme increased gizzard weight in maize-fed birds and the
      caeca of those fed wheat were heavier. The higher enzyme dose decreased duodenal
      temperature. In summary of VFA data, wheat-based diets produced more total VFAs
      and the total amount also increased with enzyme. 4. It appears from this study
      that there is equal potential in both wheat and maize diets for xylanase to
      improve performance of broilers probably through different mechanisms.

PMID- 24579791
TI  - Pharmacokinetic evaluation of fingolimod for the treatment of multiple sclerosis.
AB  - INTRODUCTION: Fingolimod is a sphingosine 1-phosphate receptor modulator with a
      novel mechanism of action and the first oral drug approved for the treatment of
      relapsing forms of multiple sclerosis (MS). Fingolimod reduces relapses more
      effectively than intramuscular interferon beta1a and delays disability
      progression. Associated safety risks are bradyarrhythmia and atrioventricular
      block following the initial dose, requiring monitoring. AREAS COVERED: This
      article examines the characteristics of fingolimod, its pharmacokinetic
      properties and the efficacy and tolerability in MS. Information on the
      pharmacology and mechanisms of action is also provided. EXPERT OPINION:
      Fingolimod is an effective therapy for relapsing forms of MS in a convenient oral
      dose. Fingolimod may target not only inflammation but potentially also
      neurodegeneration. Antagonizing astrocyte sphingosine signaling may help explain
      the reduction in cerebral atrophy observed in Phase III trials. Long-term data
      about the safety of fingolimod are needed.

PMID- 24579792
TI  - Terminal index: a new way for precise description of topologic structure of
      highly branched polymers derived from A2 + B3 stepwise polymerization.
AB  - Terminal index (TI) was presented as a new characteristic parameter for
      quantitative description of branched and cyclic topology of highly branched
      soluble polymers derived from A2 + B3 stepwise polymerization. TI is defined as
      the ratio of terminal units of an A2 + B3 type highly branched polymer to those
      in its perfect hyperbranched counterpart. TI is concisely represented as T/(D +
      L), which can be conveniently calculated from a quantitative NMR spectrum. The
      model of soluble A2 + B3 type polymers is suggested as an intermediate between
      multicyclic polymers and perfect hyperbranched polymers. The TI ranges between 0
      and 1 where a higher TI indicates a perfect hyperbranched topology while a low TI
      indicates a multicyclic structure. The analysis of soluble A2 + B3 type
      polyesters and polycarbosilanes as model polymers demonstrates that TI as a more
      precise parameter, along with degree of branching, can be generally applied to
      understand the fine topology of highly branched polymers derived from A2 + B3
      polymerization. 

PMID- 24579784
TI  - Long-term effects of chromatin remodeling and DNA damage in stem cells induced by
      environmental and dietary agents.
AB  - The presence of histones acts as a barrier to protein access; thus chromatin
      remodeling must occur for essential processes such as transcription and
      replication. In conjunction with histone modifications, DNA methylation plays
      critical roles in gene silencing through chromatin remodeling. Chromatin
      remodeling is also interconnected with the DNA damage response, maintenance of
      stem cell properties, and cell differentiation programs. Chromatin modifications
      have increasingly been shown to produce long-lasting alterations in chromatin
      structure and transcription. Recent studies have shown environmental exposures in
      utero have the potential to alter normal developmental signaling networks,
      physiologic responses, and disease susceptibility later in life during a process
      known as developmental reprogramming. In this review we discuss the long-term
      impact of exposure to environmental compounds, the chromatin modifications that
      they induce, and the differentiation and developmental programs of multiple stem
      and progenitor cell types altered by exposure. The main focus is to highlight
      agents present in the human lifestyle that have the potential to promote
      epigenetic changes that impact developmental programs of specific cell types, may
      promote tumorigenesis through altering epigenetic marks, and may be
      transgenerational, for example, those able to be transmitted through multiple
      cell divisions. 

PMID- 24579793
TI  - A new taxane diterpenoid from Taxus chinensis var. mairei.
AB  - Taxadiene (3), a new taxane diterpenoid with an unusual hydroxy substituting at C
      17, and six known compounds including two taxane diterpenoids (1 and 2) and four
      flavonoids (4-7) were isolated from the whole seedling of the Taxus chinensis
      var. mairei. Among them, compound 7 was isolated from T. chinensis var. mairei
      for the first time. Structures of these compounds were elucidated on the basis of
      spectroscopic data and by comparison with reported literature data. 

PMID- 24579794
TI  - 2013 JOSPT Award recipients highlight the need to leverage patient expectations
      and prevent second anterior cruciate ligament injuries.
AB  - During the American Physical Therapy Association's Combined Sections Meeting in
      Las Vegas, Nevada in February 2014, JOSPT recognized the authors of the most
      outstanding research and clinical practice manuscripts published in JOSPT during
      the 2013 calendar year. The 2013 JOSPT Excellence in Research Award was presented
      to Mark D. Bishop, Joel E. Bialosky, Paul Mintken, PT, DPT, and Joshua A.
      Cleland, PT, PhD for their paper titled "Patient Expectations of Benefit From
      Interventions for Neck Pain and Resulting Influence on Outcomes."

PMID- 24579796
TI  - A proposed diagnostic classification of patients with temporomandibular
      disorders: implications for physical therapists.
AB  - SYNOPSIS: Physical therapists have an important role on the interprofessional
      team to provide care for people with temporomandibular disorders (TMDs).
      Diagnostic classification is a challenge in this population, given the
      complexities inherent in presentations of headache and orofacial pain, and is
      critical to selecting the appropriate intervention. The objectives of this paper
      were (1) to characterize the epidemiology and pathophysiology of the TMDs most
      commonly seen in the outpatient clinic, (2) to describe a systems screen to be
      used in the physical therapy examination to determine the need for
      interprofessional referral, and (3) to propose an approach for physical
      therapists to examine, evaluate, and classify patients with TMDs, based on
      previously validated methodologies. A modification of the diagnostic framework of
      the International Headache Society has provided the basis for the systems screen
      of people presenting with orofacial pain. The physical therapy examination and
      evaluation is based on the Diagnostic Criteria for TMD, developed and validated
      by a consortium of specialists from the American Academy of Orofacial Pain. LEVEL
      OF EVIDENCE: Diagnosis, level 5.

PMID- 24579797
TI  - Morel-Lavallee lesion of the lumbar region.
AB  - The patient was a 21-year-old male cadet at a military academy who was evaluated
      by a physical therapist in a direct-access capacity for a chief complaint of low
      back pain that began the previous day after falling directly onto his back while
      snowboarding. Given the patient's history of trauma, worsening low back pain, and
      enlarged soft tissue mass in the lumbar region, the physical therapist ordered
      magnetic resonance imaging. The findings were consistent with a Morel-Lavallee
      lesion of the lumbar region.

PMID- 24579799
TI  - Effects of metal ions on the reactivity and corrosion electrochemistry of Fe/FeS
      nanoparticles.
AB  - Nano-zerovalent iron (nZVI) formed under sulfidic conditions results in a
      biphasic material (Fe/FeS) that reduces trichloroethene (TCE) more rapidly than
      nZVI associated only with iron oxides (Fe/FeO). Exposing Fe/FeS to dissolved
      metals (Pd(2+), Cu(2+), Ni(2+), Co(2+), and Mn(2+)) results in their
      sequestration by coprecipitation as dopants into FeS and FeO and/or by
      electroless precipitation as zerovalent metals that are hydrogenation catalysts.
      Using TCE reduction rates to probe the effect of metal amendments on the
      reactivity of Fe/FeS, it was found that Mn(2+) and Cu(2+) decreased TCE reduction
      rates, while Pd(2+), Co(2+), and Ni(2+) increased them. Electrochemical
      characterization of metal-amended Fe/FeS showed that aging caused passivation by
      growth of FeO and FeS phases and poisoning of catalytic metal deposits by
      sulfide. Correlation of rate constants for TCE reduction (kobs) with
      electrochemical parameters (corrosion potentials and currents, Tafel slopes, and
      polarization resistance) and descriptors of hydrogen activation by metals
      (exchange current density for hydrogen reduction and enthalpy of solution into
      metals) showed the controlling process changed with aging. For fresh Fe/FeS, kobs
      was best described by the exchange current density for activation of hydrogen,
      whereas kobs for aged Fe/FeS correlated with electrochemical descriptors of
      electron transfer. 

PMID- 24579800
TI  - Multiple wall in-folds sub-divide single segments during capillary regression in
      hyperoxic acute lung injury.
AB  - The present study provides further insight into the structural processes that
      remodel pulmonary capillaries in the injured adult lung. Early in hyperoxia acute
      lung injury (HALI), many sub-dividing segments are present throughout the
      capillary network before segment occlusion and loss predominate and capillary
      density decreases later in the period. A second segment sub-division triggered in
      regenerating capillaries after air breathing (post-HALI) demonstrates a similar
      mechanism of organization at a time of contrasting change in the capillary
      density. As we have previously reported, the process of segment sub-division
      includes in-folding of the endothelial-epithelial surface (alveolar-capillary
      membrane) to form inter-luminal structures (ILSs) and loops, with loop separation
      increasing segment number. Unexpectedly, the findings support remodeling of the
      capillary density by wall in-folding in acute lung injury, demonstrating a
      similar mechanism in capillary regression as well as in regeneration in the adult
      lung.

PMID- 24579801
TI  - Thymoquinone, a bioactive component of black caraway seeds, causes G1 phase cell
      cycle arrest and apoptosis in triple-negative breast cancer cells with mutant
      p53.
AB  - Thymoquinone (TQ) from black caraway seeds has several anticancer activities;
      however, its effect on triple-negative breast cancer (TNBC) cells that lack
      functional tumor suppressor p53 is not known. Here, we explored the growth
      inhibitory effect of TQ on 2 TNBC cell lines with mutant p53. Cell metabolism
      assays showed that TQ inhibited TNBC cell growth without affecting normal cell
      growth. Flow cytometric analyses of TQ-treated TNBC cells showed G1 phase cell
      cycle arrest and apoptosis characterized by the loss of mitochondrial membrane
      integrity. Western blots of lysates from TQ-treated TNBC cells showed cytochrome
      c and apoptosis-inducing factor in the cytoplasm, as well as caspase-9 activation
      consistent with the mitochondrial pathway of apoptosis. Caspase-8 was also
      activated in TQ-treated TNBC cells, although the mechanism of activation is not
      clear at this time. Importantly, TQ-induced apoptosis was only partially
      inhibited by zVAD-fmk, indicating a role for caspase-independent effector
      molecules. Poly(ADP-ribose) polymerase cleavage and increased gammaH2AX, as well
      as reduced Akt phosphorylation and decreased expression of X-linked inhibitor of
      apoptosis, were evident in TQ-treated cells. Finally, TQ enhanced cisplatin- and
      docetaxel-induced cytotoxicity. These findings suggest that TQ could be useful in
      the management of TNBC, even when functional p53 is absent. 

PMID- 24579802
TI  - PEG-PDLLA micelle treatment improves axonal function of the corpus callosum
      following traumatic brain injury.
AB  - The initial pathological changes of diffuse axonal injury following traumatic
      brain injury (TBI) include membrane disruption and loss of ionic homeostasis,
      which further lead to dysfunction of axonal conduction and axon disconnection.
      Resealing the axolemma is therefore a potential therapeutic strategy for the
      early treatment of TBI. Monomethoxy poly (ethylene glycol)-poly (D, L-lactic
      acid) di-block copolymer micelles (mPEG-PDLLA) have been shown to restore
      depressed compound action potentials (CAPs) of spinal axons and promote
      functional recovery after spinal cord injury. Here, we evaluate the effect of the
      micelles on repairing the injured cortical axons following TBI. Adult mice
      subjected to controlled cortical impact (CCI) were treated with intravenous
      injection of the micelles at 0 h or 4 h after injury. Evoked CAPs were recorded
      from the corpus callosum of coronal cortical slices at 2 days after injury. The
      CCI caused significant decreases in the amplitudes of two CAP peaks that were
      respectively generated by the faster myelinated axons and slower unmyelinated
      axons. Micelle treatment at both 0 h and 4 h after CCI resulted in significant
      increases in both CAP peak amplitudes. Injection of fluorescent dye-labeled
      micelles revealed high fluorescent staining in cortical gray and white matters
      underneath the impact site. Labeling membrane-perforated neurons by injecting a
      membrane impermeable dye Texas Red-labeled dextran into lateral ventricles at 2 h
      post-CCI revealed that immediate micelle injection after CCI did not reduce the
      number of dye-stained cortical neurons and dentate granule cells of the
      hippocampus, indicating its ineffectiveness in repairing plasma membrane of
      neuronal somata. We conclude that intravenous administration of mPEG-PDLLA
      micelles immediately or at 4 h after TBI allows brain penetration via the
      compromised blood brain-barrier, and thereby improves the function of both
      myelinated and unmyelinated axons of the corpus callosum.

PMID- 24579803
TI  - Early biochemical recurrence, urinary continence and potency outcomes following
      robot-assisted radical prostatectomy.
AB  - OBJECTIVE: The aim of this study was to describe recovery of urinary continence
      and potency and report oncological and functional outcomes using the survival,
      continence and potency (SCP) system for patients undergoing robot-assisted
      radical prostatectomy (RARP). MATERIAL AND METHODS: From 2009 to 2012, 232
      patients underwent RARP. Self-reported continence, erection sufficient for
      intercourse (ESI) and scores on the five-item version of the International Index
      of Erectile Function-5 (IIEF-5) were registered by questionnaire and physician's
      interview preoperatively and at 3, 6 and 12 month follow-up, and subsequently on
      a yearly basis. Continence was defined as 0 pads, and potency as ESI or IIEF-5
      greater than 17 with or without the aid of phosphodiesterase type 5 inhibitors.
      Oncological success was defined as absence of biochemical failure (BF) [prostate
      specific antigen (PSA) >= 0.2 ng/ml]. The SCP system was used to evaluate
      combined oncological and functional outcomes. RESULTS: In total, 184 patients
      were followed for more than 1 year. The 12 month BF-free survival rate was 97.7%.
      Median time to regain continence was 6.2 months; 12 months postoperatively 79.9%
      used 0 pads/day. Of patients with preoperative ESI, 77.6% (67.9-86.1) and 34.4%
      (24.1-47.5) maintained ESI 12 months postoperatively after bilateral and
      unilateral nerve-sparing surgery (NS), respectively. NS (p < 0.0001), increasing
      prostate volume (p = 0.014) and lower age (p < 0.0001) were positively associated
      with recovery of potency. Using the SCP system and defining potency as ESI,
      functional and oncological success 12 months after surgery was achieved in 69 out
      of 135 (51.1%) preoperative continent and potent patients who underwent
      unilateral or bilateral NS, and did not require adjuvant treatment; when defining
      potency as IIEF greater than 17, this figure was 45 out of 108 (41.7%). As
      expected, the proportions were significantly higher for bilateral than for
      unilateral NS (p <= 0.0014). CONCLUSION: RARP provides good early BF-free
      survival, continence and potency recovery rates for patients eligible for NS.

PMID- 24579804
TI  - Dorsal onlay urethroplasty using buccal mucosa graft versus penile skin flap for
      management of long anterior urethral strictures: a prospective randomized study.
AB  - OBJECTIVE: The aim of this study was to compare the outcomes of dorsal onlay
      urethroplasty using buccal mucosa graft (BMG) versus penile skin flap (PSF) in
      the repair of long anterior urethral strictures. MATERIAL AND METHODS: Patients
      with long anterior urethral strictures were randomized to receive either dorsal
      onlay BMG urethroplasty or PSF urethroplasty. All patients were evaluated
      preoperatively and during follow-up with the International Prostate Symptom Score
      (IPSS) and uroflowmetry. Success was reported when there were no obstructive
      symptoms on IPSS, with a peak urinary flow rate (Qmax) of at least 15 ml/s.
      Failure was reported in patients with obstructive symptoms, Qmax less than 15
      ml/s and evidence of recurring stricture on urethrography. RESULTS: The study
      included 19 and 18 patients in the BMG and PSF groups, respectively. The mean
      operative time was significantly shorter in the BMG than in the PSF group. The
      success rate was higher in the BMG than in the PSF group (89.5% vs 83.3%), but
      not statistically significant different. The PSF group included one case of
      extensive skin loss, three cases with superficial skin necrosis and two with
      minor penile torsion. In the BMG group, there were three cases of perioral
      numbness and another three had increased salivation. The incidence of troublesome
      postvoid urinary dribbling was significantly higher in the PSF than in the BMG
      group. After 6 months of urethroplasty, patient satisfaction was statistically
      significantly higher in the BMG than in the PSF group. CONCLUSIONS: BMG and PSF
      dorsal onlay urethroplasty had similar success rates. However, BMG is technically
      easier, takes less operative time and has a potential advantage in reducing
      postoperative morbidity, therefore leading to satisfaction for most patients.

PMID- 24579805
TI  - Effects of nickel-smelting fumes on the regulation of NIH/3T3 cell viability,
      necrosis, and expression of hMLH1 and RASSF1A.
AB  - Nickel is widely used and distributed in various industries. This study
      investigated the effect of nickel-smelting fumes on the regulation of NIH/3T3
      cell viability, apoptosis, and necrosis and the expression of the tumor
      suppressor genes hMLH1 and RASSF1A. Cell viability was determined using a
      methylthiazolyl tetrazolium colorimetric assay. NIH/3T3 cell viability was
      reduced after exposure to different concentrations of nickel-smelting fumes, but
      cell apoptosis and necrosis were induced. Moreover, cell morphology changed
      significantly after exposure to different concentrations of nickel-smelting
      fumes, as determined using an inverted microscope or transmission electron
      microscope. Real-time RT-PCR and Western blot analyses showed that exposure of
      cells to concentrations of >=100 ug/mL of nickel-smelting fumes upregulated the
      expression of hMLH1 and RASSF1A compared to the negative controls. These data
      suggest that nickel-smelting fumes could be toxic to cells, upregulating the
      expression of hMLH1 and RASSF1A and in turn inducing cell apoptosis and necrosis.

PMID- 24579806
TI  - Radiolabeling of cisplatin and its biodistribution in an experimental model of
      lung carcinogenesis.
AB  - This study optimized the radiolabeling of cisplatin with technetium-99m (99mTc)
      and evaluated its biodistribution in an experimental model of lung
      carcinogenesis. The percentage labeling of cisplatin with 99mTc was assessed
      using an ascending chromatographic technique. For biodistribution studies, male
      rats were divided into 2 groups. The control group received normal saline
      intratracheally, whereas the treatment group received intratracheal
      administration of carcinogen 7,12-dimethylbenz(a)anthracene (DMBA) at a dose of
      20 mg/kg body weight. The resulting radiopharmaceutical (99mTc-cisplatin) showed
      98% labeling efficiency and was found to be stable for up to 6 hours both in both
      serum and saline under normal conditions. The blood clearance of the 99mTc
      cisplatin followed a biphasic release pattern whereby a fast-release phase was
      observed at 35 seconds and a slow-release phase was observed after 30 minutes of
      drug administration. The biodistribution studies of control and treated animals
      revealed high uptake of 99mTc-cisplatin by the liver and slow excretion via the
      kidneys. However, a time-dependent increase in the lung-to-muscle specific uptake
      ratio was observed in DMBA-treated rats. The study concluded that 99mTc-cisplatin
      possesses selectivity toward cancerous lung tissue and can be explored further
      for its diagnostic potential in the detection of lung cancer and the evaluation
      of treatment response. 

PMID- 24579807
TI  - Toxic effects of lead exposure in rats: involvement of oxidative stress,
      genotoxic effect, and the beneficial role of N-acetylcysteine supplemented with
      selenium.
AB  - This study was carried out to investigate the in vivo protective role of N
      acetylcysteine (NAC) per se, along with selenium (Se), against lead-induced
      hepatic, nephritic-oxidative, and neuronal-oxidative damage in rats. Lead acetate
      at a dose of 50 mg/kg body weight administered intraperitoneally for 3 days was
      preferred as the source of lead. Various oxidative stress markers such as reduced
      glutathione content, lipid peroxidation, superoxide dismutase, and catalase were
      measured to determine the degree of oxidative damage and healing due to NAC (50
      mg/kg body weight administered orally) and Se (0.5 mg/kg body weight administered
      orally) and were studied along with the activities of enzymes such as
      transaminases (aspartate aminotransferase/alanine aminotransferase), delta
      aminolevulinic acid dehydratase, delta-aminolevulinic acid synthase, and acetyl
      cholinesterase activity. The genotoxic effect of lead also was studied in terms
      of DNA damage using comet assay. The effect of lead was studied in blood
      biochemical variables such as cholesterol, triglycerides, urea, uric acid, and
      creatinine. Our data suggest that supplementation of Se with NAC can improve the
      lead-induced biochemical oxidative stress in blood and tissue, the burden of lead
      on the body, and molecular alterations by recoupment in mean DNA damage. 

PMID- 24579808
TI  - Gracilaria bursa-pastoris (Gmelin) Silva extract attenuates ultraviolet B
      radiation-induced oxidative stress in human keratinocytes.
AB  - The purpose of this study was to assess the protective effects of an ethanol
      extract derived from the red alga Gracilaria bursa-pastoris (Gmelin) Silva (GBE)
      on ultraviolet B (UVB)-irradiated human HaCaT keratinocytes. GBE exhibited
      scavenging activity against intracellular reactive oxygen species that were
      induced by either hydrogen peroxide or UVB radiation. In addition, both the
      superoxide anion and the hydroxyl radical were scavenged by GBE in cell-free
      systems. GBE absorbed light in the UVB range (280-320 nm) of the electromagnetic
      spectrum and lessened the extent of UVB-induced oxidative damage to cellular
      lipids, proteins, and DNA. Finally, GBE-treated keratinocytes showed a reduction
      in UVB-induced apoptosis, as exemplified by fewer apoptotic bodies. These results
      suggest that GBE exerts cytoprotective actions against UVB-stimulated oxidative
      stress by scavenging ROS and absorbing UVB rays, thereby attenuating injury to
      cellular constituents and preventing cell death. 

PMID- 24579809
TI  - The risk factors of head and neck cancer and their general patterns in Australia:
      a descriptive review and update.
AB  - The purpose of this article is to provide a descriptive review of risk factors of
      head and neck cancer (HNC), with particular interest in their general patterns in
      Australia. All these risk factors are deeply perplexing, with socioeconomic,
      cultural, and geographic variables. We reviewed articles from PubMed, MEDLINE,
      and Google Scholar by using keywords such as risk factors, alcohol, tobacco,
      human papilloma virus (HPV), environmental risk factors, and other risk factors.
      We selected relevant articles after they completely fit into the inclusion
      criteria for this review. Previous reports highlight that smoking tobacco,
      consuming alcohol, and HPV infection are the major risk factors for HNC.
      Geographical variations in incidence rates are indicative of differences in the
      prevalence of risk factors among countries. HNC could be prevented by reducing
      the prevalence of established risk factors. 

PMID- 24579810
TI  - Acute and subacute pulmonary toxicity caused by a single intratracheal
      instillation of colloidal silver nanoparticles in mice: pathobiological changes
      and metallothionein responses.
AB  - To study the acute and subacute pulmonary toxicity of colloidal silver
      nanoparticles (Ag-NPs), 0 or 100 ppm of Ag-NPs were instilled intratracheally in
      mice. Cellular and biochemical parameters in bronchoalveolar lavage fluid (BALF)
      and histological alterations were determined 1, 3, 7, 15, and 30 days after
      instillation. Ag-NPs induced moderate pulmonary inflammation and injury on BALF
      indices during the acute period; however, these changes gradually regressed in a
      time-dependent manner. Concomitant histopathological and laminin
      immunohistochemical findings generally correlated to BALF data. Superoxide
      dismutase and metallothionein expression occurred in particle-laden macrophages
      and alveolar epithelial cells, which correlated to lung lesions in mice treated
      with Ag-NPs. These findings suggest that instillation of Ag-NPs causes transient
      moderate acute lung inflammation and tissue damage. Oxidative stress may underlie
      the induction of injury to lung tissue. Moreover, the expression of
      metallothionein in tissues indicated the protective response to exposure to Ag
      NPs. 

PMID- 24579811
TI  - On the mechanism of cellular toxicity in breast cancer by ionizing radiation and
      chemotherapeutic drugs.
AB  - Breast cancer is the second leading cause of cancer mortality and the most
      frequent cancer found in women around the globe. The development of breast cancer
      is a multistep and complicated process that includes the development of ductal
      and lobular cells into atypical hyperplasia, carcinoma in situ, and invasive
      carcinoma, with an ability to metastasize. The efficacy of radiotherapy in breast
      cancer seems to be reduced because of a frequently observed lack of cellular
      sensitivity to apoptosis. Both Bcl-2 and p53 are linked to apoptosis pathways and
      are known to play a role in the outcome of radiotherapy. Resistance of tumor
      cells to therapeutic drugs and the undesirable cytotoxicity of normal cells are
      frequently observed in treatment outcomes in clinics. Research is, therefore,
      needed to develop strategies for improving the protocols of chemotherapy and
      radiotherapy in patients with breast cancer. This review focuses on understanding
      the molecular mechanisms of enhanced tumor cell killing by the combined action of
      certain anticancer drugs together with gamma radiation in vitro, with possible
      implications for practical applications in clinics. 

PMID- 24579812
TI  - Multiplex DNA assay based on nanoparticle probes by single particle inductively
      coupled plasma mass spectrometry.
AB  - A multiplex DNA assay based on nanoparticle (NP) tags detection utilizing single
      particle mode inductively coupled plasma mass spectrometry (SP-ICP-MS) as
      ultrasensitive readout has been demonstrated in the article. Three DNA targets
      associated with clinical diseases (HIV, HAV, and HBV) down to 1 pM were detected
      by DNA probes labeled with AuNPs, AgNPs, and PtNPs via DNA sandwich assay. Single
      nucleotide polymorphisms in genes can also be effectively discriminated. Since
      our method is unaffected by the sample matrix, it is well-suited for diagnostic
      applications. Moreover, with the high sensitivity of SP-ICP-MS and the variety of
      NPs detectable by SP-ICP-MS, high-throughput DNA assay could be achieved without
      signal amplification or chain reaction amplification. 

PMID- 24579813
TI  - Nemonoxacin (TG-873870) for treatment of community-acquired pneumonia.
AB  - With a broad-spectrum of activity, fluoroquinolones have been widely and
      successfully used for decades for the treatment of and prophylaxis against
      various bacterial infections, including community-acquired pneumonia (CAP).
      However, the use of fluoroquinolones has been compromised by the emergence and
      spreading of bacterial resistance and the potential for adverse effects.
      Therefore, there is an unmet need for newer compounds that have a broader
      spectrum of activity to overcome existing bacterial resistance as well as the
      potential to minimize the risk of adverse effects. Nemonoxacin (TG-873870), a
      newly developed quinolone, has demonstrated broad-spectrum activity against Gram
      positive, Gram-negative and atypical pathogens, including drug-resistant
      Streptococcus pneumoniae and methicillin-resistant Staphylococcus aureus. Results
      from Phases I and II studies of treatment of CAP are encouraging. This article
      reviews the updated data on nemonoxacin, including the bacterial susceptibility,
      the pharmacologic characteristics, and toxicities, and clinical trials using
      nemonoxacin for treatment of CAP. 

PMID- 24579814
TI  - Phenotypic analysis of chemokine-driven actin reorganization in primary human
      neutrophils.
AB  - The chemokine-driven activation of CXC-type chemokine receptors 1/2 (CXCR1/2) and
      the subsequent reorganization of the neutrophilic actin are early key events in
      the induction of neutrophil migration toward centers of inflammation. In this
      study, an image analysis algorithm was developed to detect subtle chemokine
      induced changes in the actin cytoskeleton of primary human neutrophils. By this
      means, a discrete early step of neutrophil activation was dissected that could be
      initiated by concentrations of growth-related oncogen alpha (Gro-alpha) or
      interleukin-8 (IL-8) just above their resting-state plasma levels. The associated
      half-maximal effective concentration (EC50) values for Gro-alpha and IL-8 of 8
      and 22 pM, respectively, are between two and three orders of magnitude below the
      so-far reported EC50 values of these chemokines for the induction of neutrophilic
      calcium release, integrin expression, degranulation, and receptor
      internalization. Sch527123, a known inhibitor of CXCR2 (KD=49 pM) and with a
      lower potency/affinity also of CXCR1 (KD=3.9 nM), antagonized actin remodeling
      with half-maximal inhibitory concentration (IC50) values of 400 pM for the CXCR2
      specific agonist Gro-alpha and of 36 nM for the CXCR1/2-promiscuous agonist IL-8.
      This observation indicates that the here-described early step of chemokine-driven
      actin reorganization is modulated by both CXCR1 and CXCR2. Thus, the imaging
      based assay format, as developed in this work, may be employed in a phenotypic
      screening campaign to identify inhibitors of an early step in CXCR1/2-induced
      neutrophilic chemotaxis.

PMID- 24579815
TI  - Effects of feeding programme and feeder space change at photo-stimulation using
      maize- or wheat-based diet on growth and reproductive performance of female
      broiler breeders.
AB  - 1. This study was carried out to determine the effects of breeder feeding
      programme to 29 weeks of age, and feeder space change at photo-stimulation using
      two sources of grain on breeder hen reproductive efficiency and egg
      characteristics. 2. Fast-feathering Cobb 500 pullet broiler breeders were housed
      in 16 pens of 81 females each during rearing, and fed on either maize- or wheat
      based diet, formulated to have similar nutrient composition. Two feeding
      programmes, Fast and Slow, were used from 14 to 29 weeks of age. At 22 weeks of
      age, 69 females that represented the body weight (BW) distribution from each pen
      were placed in a layer house where feeder space either remained very similar
      (from 6.3 to 6.5 cm/female) or was increased (from 6.3 to 8.4 cm/female). Breeder
      growth performance, reproductive efficiency and egg characteristics were
      evaluated. 3. Data were analysed as a 2 * 2 * 2 factorial design with diet type,
      feeding programme and feeder space change as the main factors. The main effects
      of the treatments were found but there were no treatment interactions. 4.
      Breeders fed on wheat were consistently heavier than breeders fed on maize from
      10 to 52 weeks of age and exhibited greater hen mortality during the layer phase.
      Breeders fed on wheat diets exhibited improved egg production while laying eggs
      with a greater yolk:albumen ratio compared to the maize group. 5. The Fast
      feeding programme increased female mortality and increased BW during the layer
      phase. Breeders fed according to the Slow feeding programme had better fertility,
      and laid eggs with lower percentage eggshell that might be associated with the
      lower early embryonic mortality observed in these hens as compared with the Fast
      feeding programme. 6. Breeders having increased feeder space at photo-stimulation
      matured earlier and produced more eggs compared to breeders with no change in
      feeder space. 7. It was concluded that the feeding of wheat, the use of the Slow
      feeding programme and an increase in feeder space improved some aspects of hen
      productivity and egg characteristics.

PMID- 24579816
TI  - The contribution of platelet studies to the understanding of disease mechanisms
      in complex and monogenetic neurological disorders.
AB  - Platelets, known for their role in primary haemostasis, prevent excessive
      bleeding after injury. The study of platelets has, therefore, traditionally
      focused on bleeding disorders. It has recently become evident, however, that
      platelet research can contribute to unravelling the disease mechanisms that
      underlie neuropathological disorders that have a subtle subclinical platelet
      phenotype. Platelets and neurosecretory cells have common gene expression
      profiles and share several biological features. This review provides a literature
      update on the use of platelets as easily accessible cells to study neurological
      disorders. We provide examples of the use of different platelet-based tests to
      understand the underlying pathophysiological mechanisms for both complex and
      monogenetic neuropathological disorders. In addition to the well-studied
      regulated granule secretion and serotonin metabolism, more recent studies have
      shown that defects in transcription factors, membrane transporters, G-protein
      signal transduction, and cytoskeletal proteins can be investigated using
      platelets to gain information on their role in neuropathology. 

PMID- 24579817
TI  - A new modified sesquiterpene glycoside from Cupressus chengiana.
AB  - A new sesquiterpene glycoside, cupressusoside (1), and five known compounds were
      isolated from the 70% aqueous ethanol extract of the branches and leaves of
      Cupressus chengiana. Their structures were elucidated by using spectroscopic
      methods. All the isolates expressed no remarkable cytotoxic activity against
      colon carcinoma (HCT-8) and breast cancer (MCF-7) cell lines, with IC50>40 mg/mL.

PMID- 24579818
TI  - Destruction of the arrector pili muscle and fat infiltration in androgenic
      alopecia.
AB  - BACKGROUND: Androgenic alopecia (AGA) is the most common hair loss condition in
      men and women. Hair loss is caused by follicle miniaturization, which is largely
      irreversible beyond a certain degree of follicular regression. In contrast, hair
      loss in telogen effluvium (TE) is readily reversible. The arrector pili muscle
      (APM) connects the follicle to the surrounding skin. OBJECTIVES: To compare
      histopathological features of the APM in AGA and TE. METHODS: Archival blocks of
      4-mm scalp punch biopsies from eight patients with AGA and five with TE were
      obtained. New 4-mm biopsies from five normal cases were used as controls. Serial
      7-MUm sections were stained with a modified Masson's trichrome stain.
      'Reconstruct' software was used to construct and evaluate three-dimensional
      images of the follicle and APM. RESULTS: The APM degenerated and was replaced by
      adipose tissue in all AGA specimens. Remnants of the APM remained attached to the
      hair follicle. There was no fat in the normal skin specimens. Fat was seen in two
      of five TE specimens but could be attributed to these patients also showing
      evidence of AGA. Quantitative analysis showed that muscle volume decreased and
      fat volume increased significantly (P < 0.05) in AGA compared with controls.
      CONCLUSIONS: APM degeneration and replacement with fat in AGA has not previously
      been described. The underlying mechanism remains to be determined. However, we
      speculate that this phenomenon might be related to depletion of stem or
      progenitor cells from the follicle mesenchyme, explaining why AGA is treatment
      resistant.

PMID- 24579819
TI  - Chemometric determination of the botanical origin for Chinese honeys on the basis
      of mineral elements determined by ICP-MS.
AB  - In this work, the potential of mineral elements and chemometric methods as a tool
      to classify Chinese honeys according to their botanical origin was examined.
      Twelve mineral elements (Na(23), Mg(24), P(31), K(39), Ca(43), Mn(55), Fe(56),
      Cu(63), Zn(66), Rb(85), Sr(88), and Ba(137)) of 163 Chinese honey samples,
      including linden, vitex, rape, and acacia, collected from Heilongjiang, Beijing,
      Hebei, and Shaanxi, China, in 2013 were determined by the ICP-MS method.
      Principal component analysis (PCA) reduced 10 variables to four principal
      components and could explain 93.06% of the total variance. Partial least-squares
      discriminant analysis (PLS-DA) and back-propagation artificial neural network (BP
      ANN) were explored to construct a classification model. By PLS-DA, the total
      correct classification rates for model training and cross-validation were 90.9
      and 88.4%, respectively. By BP-ANN, the total correct classification rates for
      model training and cross-validation were 100 and 92.6%, respectively. The
      performance of BP-ANN was better than that of PLS-DA. The validation of the
      developed BP-ANN model was tested by the independent test set of 42 honey
      samples. Linden, vitex, and rape honey samples were predicted with an accuracy of
      100%, whereas one acacia honey was predicted as rape honey with an accuracy of
      92.3%. It is concluded that the profiles of mineral elements by ICP-MS with
      chemometric methods could be a potential and powerful tool for the classification
      of Chinese honey samples from different botanical origins.

PMID- 24579820
TI  - Development and initial assessment of a training program for laparoscopic radical
      prostatectomy. First module: the urethrovesical anastomosis.
AB  - PURPOSE: We present our experience in the design and development of a training
      program in laparoscopic radical prostatectomy (LRP), and the validation of the
      first steps of the program by objective measurement of the attendants' skills
      improvement and subjective evaluation of its contents. MATERIALS AND METHODS: Our
      training model on LRP has a total duration of 42 hours, divided in two modules of
      21 hours each, performed 1 month apart. Data included in the present study were
      obtained from the first module of our course. It begins with acquisition of basic
      knowledge in ergonomics and instrument concepts, after which the attendants
      develop essential laparoscopic dexterities through the performance of hands-on
      physical simulator tasks. During the second and third day, urologists performed
      urethrovesical anastomosis also in the physical simulator. Attendants' skills
      improvement was measured during the first module by registering surgical times
      and suturing quality of the anastomosis, the latter by means of a leak test. At
      the end of the training program, a subjective evaluation questionnaire on the
      different didactic and organizational aspects was handed out to the attendants.
      RESULTS: By comparing first and last anastomosis, we observed a significant
      decrease in surgical times (minutes) (T1 40.1+/-4.6 vs T6 24.01+/-3.34; P<=0.005)
      and an increase in intraluminal leak pressure (mm Hg) (T1 8.27+/-7.33 vs T6
      21.09+/-6.72; P<=0.005). We obtained a highly positive score on all questions
      concerning the different topics and techniques included in the training program
      (>=9 points over 10). Regarding the attendants' self-assessment of acquired
      abilities, 78.3% considered themselves capacitated to perform the trained
      procedures on patients. CONCLUSIONS: Training obtained during the first module of
      our training model significantly decreased performance times for ex vivo
      urethrovesical anastomosis, simultaneously increasing its quality. In addition,
      validation of the training model was also demonstrated by the highly scored
      evaluation resulting from the attendants' assessment.

PMID- 24579821
TI  - Shifting attention between the space of the body and external space:
      electrophysiological correlates of visual-nociceptive crossmodal spatial
      attention.
AB  - The study tested whether nociceptive stimuli applied to a body limb can orient
      spatial attention in external space toward visual stimuli delivered close to that
      limb. Nociceptive stimuli were applied to either the left or the right hand. Task
      relevant visual stimuli were delivered at the location adjacent to the stimulated
      hand (70% valid trials) or adjacent to the other hand (30% invalid trials).
      Visual stimuli were discriminated with shorter reaction times and elicited ERPs
      of greater magnitude in the valid as compared to the invalid trials. This
      enhancement affected the N1 component, suggesting that the location of the
      nociceptive cue modifies visual processing through a modulation of neural
      activity in the visual cortex. We hypothesize the existence of a common frame of
      reference able to coordinate the mapping of the space of the body and the mapping
      of the external space. 

PMID- 24579822
TI  - Human herpesvirus-6 encephalopathy after hematopoietic stem cell transplantation
      and class I human leukocyte antigen.
AB  - Human herpesvirus-6 (HHV-6) encephalopathy is a serious complication of
      allogeneic hematopoietic stem cell transplantation (allo-HSCT). Although
      reactivation of HHV-6 is often observed after allo-HSCT, encephalopathy only
      affects a few patients with HHV-6 reactivation. Human leukocyte antigen (HLA)
      class I is expressed by most somatic cells, and a relationship between some class
      I alleles and neurological diseases has been reported. The HHV-6 load at two,
      three, and four weeks after allo-HSCT was examined. HHV-6 encephalopathy was
      diagnosed from symptoms, results of cerebrospinal fluid examination, and magnetic
      resonance imaging findings. The relation between HHV-6 reactivation or
      encephalopathy and the HLA class I status of the recipients was investigated. In
      130 patients, 147 allo-HSCT transplantation procedures were carried out. HHV-6
      reactivation and encephalopathy occurred in 56 and nine procedures, respectively.
      HLA mismatch (p = 0.008) and unrelated donor (p = 0.001) were associated with HHV
      6 reactivation, but not with HHV-6 encephalopathy. HHV-6 encephalopathy was more
      frequent in patients with HLA-B*40:06 (p = 0.027). In addition, HLA-A*26:01 and
      HLA-B*40:06 were found to be associated with each other (p = 0.089), while HLA
      B*40:06 and HLA-C*08:01 showed a significant association (p < 0.001). The HLA
      class I alleles of recipients may be associated with the occurrence of HHV-6
      encephalopathy after allo-HSCT.

PMID- 24579823
TI  - Helping patients with serious illness live well through the promotion of adaptive
      coping: a report from the improving outpatient palliative care (IPAL-OP)
      initiative.
AB  - Continuity outpatient palliative care practice is characterized by long
      relationships between patients, families, and palliative care clinicians and by
      periods of relative stability when the disease and resultant symptoms are less
      active. Compared to inpatient palliative care, outpatient practice requires a
      greater focus on encouraging healthy coping and on helping patients to live well
      with serious illness. This paper discusses the opportunities to promote adaptive
      coping in the delivery of outpatient palliative care.

PMID- 24579824
TI  - Human SOD1-G93A specific distribution evidenced in murine brain of a transgenic
      model for amyotrophic lateral sclerosis by MALDI imaging mass spectrometry.
AB  - Amyotrophic lateral sclerosis (ALS) is a progressive, fatal neurodegenerative
      disease caused by the degeneration of motor neurons. The transgenic mouse model
      carrying the human SOD1G93A mutant gene (hSOD1G93A mouse) represents one of the
      most reliable and widely used model of this pathology. In the present work, the
      innovative technique of matrix-assisted laser desorption/ionization (MALDI)
      imaging mass spectrometry (IMS) was applied in the study of pathological
      alterations at the level of small brain regions such as facial and trigeminal
      nuclei, which in rodents are extremely small and would be difficult to analyze
      with classical proteomics approaches. Comparing slices from three mice groups
      (transgenic hSOD1G93A, transgenic hSOD1WT, and nontransgenic, Ntg), this
      technique allowed us to evidence the accumulation of hSOD1G93A in the facial and
      trigeminal nuclei, where it generates aggregates. This phenomenon is likely to be
      correlated to the degeneration observed in these regions. Moreover, a statistical
      analysis allowed us to highlight other proteins as differentially expressed among
      the three mice groups analyzed. Some of them were identified by reverse-phase
      HPLC fractionation of extracted proteins and mass spectrometric analysis before
      and after trypsin digestion. In particular, the 40S ribosomal protein S19 (RPS19)
      was upregulated in the parenkyma and reactive glial cells in facial nuclei of
      hSOD1G93A mice when compared to transgenic hSOD1WT and nontransgenic ones. 

PMID- 24579825
TI  - Modification of Fatty acids in membranes of bacteria: implication for an adaptive
      mechanism to the toxicity of carbon nanotubes.
AB  - We explored whether bacteria could respond adaptively to the presence of carbon
      nanotubes (CNTs) by investigating the influence of CNTs on the viability,
      composition of fatty acids, and cytoplasmic membrane fluidity of bacteria in
      aqueous medium for 24 h exposure. The CNTs included long single-walled carbon
      nanotubes (L-SWCNTs), short single-walled carbon nanotubes (S-SWCNTs), short
      carboxyl single-walled carbon nanotubes (S-SWCNT-COOH), and aligned multiwalled
      carbon nanotubes (A-MWCNTs). The bacteria included three common model bacteria,
      Staphyloccocus aureus (Gram-positive), Bacillus subtilis (Gram-positive), and
      Escherichia coli (Gram-negative), and one polybrominated diphenyl ether degrading
      strain, Ochrobactrum sp. (Gram-negative). Generally, L-SWCNTs were the most toxic
      to bacteria, whereas S-SWCNT-COOH showed the mildest bacterial toxicity.
      Ochrobactrum sp. was more susceptible to the toxic effect of CNTs than E. coli.
      Compared to the control in the absence of CNTs, the viability of Ochrobactrum sp.
      decreased from 71.6-81.4% to 41.8-70.2%, and E. coli from 93.7-104.0% to 67.7
      91.0% when CNT concentration increased from 10 to 50 mg L(-1). The cytoplasmic
      membrane fluidity of bacteria increased with CNT concentration, and a significant
      negative correlation existed between the bacterial viabilities and membrane
      fluidity for E. coli and Ochrobactrum sp. (p < 0.05), indicating that the
      increase in membrane fluidity induced by CNTs was an important factor causing the
      inactivation of bacteria. In the presence of CNTs, E. coli and Ochrobactrum sp.
      showed elevation in the level of saturated fatty acids accompanied with reduction
      in unsaturated fatty acids, compensating for the fluidizing effect of CNTs. This
      demonstrated that bacteria could modify their composition of fatty acids to adapt
      to the toxicity of CNTs. In contrast, S. aureus and B. subtilis exposed to CNTs
      increased the proportion of branched-chain fatty acids and decreased the level of
      straight-chain fatty acids, which was also favorable to counteract the toxic
      effect of CNTs. This study suggests that the bacterial tolerances to CNTs are
      associated with both the adaptive modification of fatty acids in the membrane and
      the physicochemical properties of CNTs. This is the first report about the
      physiologically adaptive response of bacteria to CNTs, and may help to further
      understand the ecotoxicological effects of CNTs. 

PMID- 24579827
TI  - Furanodendralenes.
AB  - An examination of Diels-Alder reactions of furan-containing analogues of
      dendralenes has revealed complex and fascinating reaction sequences, which chart
      the inherent site and stereoselectivity of these processes and give rapid access
      to structures of high molecular complexity. 

PMID- 24579826
TI  - In vitro and in vivo antitumor activity of Bulbus Fritillariae Cirrhosae and
      preliminary investigation of its mechanism.
AB  - Bulbus Fritillariae Cirrhosae (BFC) is widely used in China both for food and
      folk medicine because of its powerful biological activities. Firstly, this study
      was designed to examine the antiproliferative activities of the different
      fractions from BFC in vitro by MTT assay. The results showed that chloroform
      extracts (CE) and the purified total alkaloids of BFC (TAF) exhibited stronger
      antiproliferative activity than the other fractions. We further determined the
      total alkaloids and 3 main alkaloids monomers content of CE and TAF by UV and
      HPLC-ELSD methods, respectively. Moreover, we assessed the antitumor activity of
      TAF in vivo and made preliminary investigation of its antitumor mechanism by
      histological and immunohistochemical staining technique. These results
      demonstrate that TAF showed significant antitumor activity and low toxicity in
      vivo. Meanwhile, TAF significantly inhibited tumor angiogenesis and induced
      apoptosis by improvement of expression level of caspase-3. These results suggest
      that alkaloids of BFC could hold a good potential for use as an antitumor drug. 

PMID- 24579828
TI  - Multiple mitochondrial alterations in a case of myopathy.
AB  - Mitochondrial alterations are the most common feature of human myopathies. A
      biopsy of quadriceps muscle from a 50-year-old woman exhibiting myopathic
      symptoms was examined by transmission electron microscopy. Biopsied fibers from
      quadriceps muscle displayed numerous subsarcolemmal mitochondria that contained
      crystalloids. Numbering 1-6 per organelle, these consisted of rows of punctuate
      densities measuring ~0.34 nm; the parallel rows of these dots had a periodicity
      of ~0.8 nm. The crystalloids were ensconced within cristae or in the outer
      compartment. Some mitochondria without crystalloids had circumferential cristae,
      leaving a membrane-free center that was filled with a farinaceous material. Other
      scattered fibrocyte defects included disruption of the contractile apparatus or
      its sporadic replacement by a finely punctuate material in some myofibers.
      Intramitochondrial crystalloids, although morphologically striking, do not impair
      organelle physiology to a significant degree, so the muscle weakness of the
      patient must originate elsewhere.

PMID- 24579829
TI  - Host species and developmental stage, but not host social structure, affects
      bacterial community structure in socially polymorphic bees.
AB  - Social transmission and host developmental stage are thought to profoundly affect
      the structure of bacterial communities associated with honey bees and bumble
      bees, but these ideas have not been explored in other bee species. The halictid
      bees Megalopta centralis and M. genalis exhibit intrapopulation social
      polymorphism, which we exploit to test whether bacterial communities differ by
      host social structure, developmental stage, or host species. We collected social
      and solitary Megalopta nests and sampled bees and nest contents from all stages
      of host development. To survey these bacterial communities, we used 16S rRNA gene
      454 pyrosequencing. We found no effect of social structure, but found differences
      by host species and developmental stage. Wolbachia prevalence differed between
      the two host species. Bacterial communities associated with different
      developmental stages appeared to be driven by environmentally acquired bacteria.
      A Lactobacillus kunkeei clade bacterium that is consistently associated with
      other bee species was dominant in pollen provisions and larval samples, but less
      abundant in mature larvae and pupae. Foraging adults appeared to often reacquire
      L. kunkeei clade bacteria, likely while foraging at flowers. Environmental
      transmission appears to be more important than social transmission for Megalopta
      bees at the cusp between social and solitary behavior.

PMID- 24579830
TI  - Distinguishing analyte from noise components in mass spectra of complex samples:
      where to cut the noise?
AB  - Fourier transform mass spectrometry (FTMS) enables comprehensive analysis of
      complex molecular mixtures. Given the broad intensity ranges of components in the
      mass spectra, it is imperative to accurately determine a noise threshold level
      above which peak assignments will be made. Conventionally, to find the threshold
      level, the "N sigma" approach or an equivalent rule is used. However, the "N
      sigma" approach cannot be applied to mass spectra stored with partially removed
      noise (reduced-profile mode). It is also not directly applicable to mass spectra
      acquired in the absorption mode with removed negative spectral amplitudes.
      Moreover, N value selection is normally made based on a rule of thumb, meaning
      that the calculated threshold level may be biased. Here, we present a noise
      thresholding method which addresses these limitations for analysis of mass
      spectra of complex molecular mixtures. The introduced data-dependent thresholding
      method involves analysis of the distribution of logarithmic intensity of all
      peaks, including noise and analyte, for a given mass spectrum. Selected method
      applications include FTMS analysis of crude oil fractions as well as tandem MS
      analysis of intact proteins. 

PMID- 24579831
TI  - Working memory training with tDCS improves behavioral and neurophysiological
      symptoms in pilot group with post-traumatic stress disorder (PTSD) and with poor
      working memory.
AB  - This pilot study investigated the feasibility of treating people suffering from
      both post-traumatic stress disorder (PTSD) and poor working memory by employing a
      combination of computerized working memory training and transcranial direct
      current stimulation (tDCS). After treatment, all four participants showed
      clinically significant improvements on a range of cognitive and emotional
      performance measures. Moreover, these improvements were accompanied by
      theoretically significant neurophysiological changes between pre- and post
      treatment electroencephalographic (EEG) recordings. Specifically, the P3a
      component of participants' event related potentials (ERP) in response to novelty
      stimuli, characteristically abnormal in this clinical population, shifted
      significantly toward database norms. So, participants' initially slow alpha peak
      frequency (APF), theorized to underlie impaired cognitive processing abilities,
      also increased in both frequency and amplitude as a result of treatment. On the
      basis of these promising results, more extensive controlled studies are
      warranted. 

PMID- 24579833
TI  - From gene variants to novel therapies. Is the prostaglandin e2 pathway in primary
      graft dysfunction ready for prime time?

PMID- 24579834
TI  - Bronchiectasis severity: time to score.

PMID- 24579835
TI  - Lung clearance index. A potential quantitative tool to assess treatment response
      in bronchiectasis?

PMID- 24579836
TI  - Babesiosis.

PMID- 24579837
TI  - Differences in right ventricular remodeling secondary to pressure overload in
      patients with pulmonary hypertension.

PMID- 24579838
TI  - Nebulized liposomal amphotericin B for treating Aspergillus empyema with
      bronchopleural fistula.

PMID- 24579839
TI  - Inhaled granulocyte/macrophage colony-stimulating factor as treatment of
      pneumonia-associated acute respiratory distress syndrome.

PMID- 24579840
TI  - Use of resuscitation-promoting factor proteins improves the sensitivity of
      culture-based tuberculosis testing in special samples.

PMID- 24579841
TI  - Club cell protein and chronic obstructive pulmonary disease progression: the
      unrealized potential of a peripheral lung biomarker.

PMID- 24579842
TI  - Reply: Club cell protein and chronic obstructive pulmonary disease progression:
      the unrealized potential of a peripheral lung biomarker.

PMID- 24579843
TI  - Giant saphenous vein coronary artery bypass graft aneurysm.

PMID- 24579844
TI  - Patient information series. Sudden breathlessness crisis.

PMID- 24579845
TI  - Thoughts on clinical teaching and learning.

PMID- 24579846
TI  - Introducing students to evidence-based practice and quality measures.

PMID- 24579847
TI  - Quality and safety education for nurses becomes collaborative: out of the silo.

PMID- 24579848
TI  - Antiurease activity of plants growing in the Czech Republic.
AB  - The antiurease activity of the aqueous extracts of 42 plants growing in the Czech
      Republic was investigated. A phenol-hypochlorite reaction was used for the
      determination of ammonia produced by urease. The inhibitory activity of the
      extracts at a concentration of 0.2 mg/mL varied from 17.8% to 80.0%. Extracts
      from six Potentilla species expressed inhibitory activity against jack bean
      urease. They were further investigated for their phenolic constituents and the
      major compounds were subjected to molecular docking. The results revealed that
      both jack bean urease and Helicobacter pylori urease were inhibited by quercetin
      3-O-beta-D-galactopyranoside-6"-gallate (1), myricetin-3-O-beta-D-glucuronide
      (2), tiliroside (3) and B-type procyanidin (4). The antiurease activity of the
      investigated Potentilla species is probably due to the presence of complex
      phenolic constituents such as flavonoid glycosides and catechin dimers.

PMID- 24579850
TI  - Treatment of bacterial vaginosis: what we have and what we miss.
AB  - INTRODUCTION: The disturbing, foul-smelling discharge of bacterial vaginosis (BV)
      is a nuisance to women. Treatment possibilities for BV are limited and only
      achieve complete cure in 65 to 85% of cases. In most women, the condition
      relapses within weeks to months after treatment. AREAS COVERED: In search of new
      therapeutic actions to cure, prevent or delay recurrences of BV, PubMed and web
      of science were searched for papers with i) decent study layout, ii) proper
      statistics, iii) comparison group (placebo or standard treatment) and iv)
      language English, French, Dutch or German. The following keywords were used:
      bacterial vaginosis and treatment or management or therapy or prophylaxis or
      prevention. Results were grouped in treatment categories and were discussed.
      EXPERT OPINION: Clindamycin and metronidazole are the standard drugs for BV. As
      other antibiotic and acidifying treatments are progressively being studied, like
      tinidazole, rifaximin, nitrofuran, dequalinium chloride, vitamin C and lactic
      acid, more options have become available for switching therapy, combining
      therapies and long-term prophylactic use to prevent recurrences. Further studies
      are needed. Also, adjuvant therapy with probiotics may have a significant role in
      improving efficacy and in preventing recurrences. However, it is unlikely that
      probiotics will replace antibiotherapy.

PMID- 24579849
TI  - Reconciling discrepant findings for P3 brain response in criminal psychopathy
      through reference to the concept of externalizing proneness.
AB  - We sought to address inconsistencies in the literature on amplitude of P3 brain
      potential response in offenders diagnosed with psychopathy. These inconsistencies
      contrast with the reliable finding of reduced P3 in relation to externalizing
      tendencies, which overlap with impulsive-antisocial features of psychopathy, as
      distinguished from the affective-interpersonal features. Employing a sample of
      incarcerated male offenders (N = 154) who completed the Psychopathy Checklist
      Revised along with a three-stimulus visual oddball task, we tested the hypothesis
      that impulsive-antisocial features of psychopathy would selectively exhibit an
      inverse relationship with P3 amplitude. Clear support for this hypothesis was
      obtained. Our findings clarify the discrepant findings regarding psychopathy and
      P3, and establish P3 as a neurophysiological point of contact between psychopathy
      and externalizing proneness from the broader psychopathology literature.

PMID- 24579851
TI  - Digital encoding of cellular mRNAs enabling precise and absolute gene expression
      measurement by single-molecule counting.
AB  - We present a new approach for the sensitive detection and accurate quantitation
      of messenger ribonucleic acid (mRNA) gene transcripts in single cells. First, the
      entire population of mRNAs is encoded with molecular barcodes during reverse
      transcription. After amplification of the gene targets of interest, molecular
      barcodes are counted by sequencing or scored on a simple hybridization detector
      to reveal the number of molecules in the starting sample. Since absolute
      quantities are measured, calibration to standards is unnecessary, and many of the
      relative quantitation challenges such as polymerase chain reaction (PCR) bias are
      avoided. We apply the method to gene expression analysis of minute sample
      quantities and demonstrate precise measurements with sensitivity down to sub
      single-cell levels. The method is an easy, single-tube, end point assay utilizing
      standard thermal cyclers and PCR reagents. Accurate and precise measurements are
      obtained without any need for cycle-to-cycle intensity-based real-time monitoring
      or physical partitioning into multiple reactions (e.g., digital PCR). Further,
      since all mRNA molecules are encoded with molecular barcodes, amplification can
      be used to generate more material for multiple measurements and technical
      replicates can be carried out on limited samples. The method is particularly
      useful for small sample quantities, such as single-cell experiments. Digital
      encoding of cellular content preserves true abundance levels and overcomes
      distortions introduced by amplification. 

PMID- 24579852
TI  - Control of Clostridium difficile infection in the hospital setting.
AB  - Clostridium difficile infection (CDI) has emerged as a leading challenge in the
      control of healthcare-associated infection (HCAI). The epidemiology of CDI has
      changed dramatically, this is associated with emergence of 'hypervirulent'
      strains, particularly PCR ribotype 027. Despite the epidemic spread of these
      strains, there are recent reports of decreasing incidence from healthcare
      facilities where multi-facetted targeted control programs have been implemented.
      We consider these changes in epidemiology and reflect on the tools available to
      control CDI in the hospital setting. The precise repertoire of measures adopted
      and emphasis on different interventions will vary, not only between healthcare
      systems, but also within different institutions within the same healthcare
      system. Finally, we consider both the sustainability of reductions already
      achieved, and the potential to reduce CDI further. This takes account of newly
      emerging data on more recent changes in the epidemiology of CDI, and the
      potential of novel interventions to decrease the burden of disease. 

PMID- 24579853
TI  - The natural history of knee osteoarthritis: India-based knee osteoarthritis
      evaluation (iKare): a study protocol.
AB  - METHODOLOGY: Multi-center, cross-sectional, observational study. STUDY CENTER(S):
      Multiple centers in India. NUMBER OF PARTICIPANTS: 1,000. PRIMARY RESEARCH
      OBJECTIVE: To characterize patients and treatment utilized for orthopedic
      patients presenting to both private and public hospital centers in India with
      knee pain and symptoms suggestive of knee arthritis. INCLUSION CRITERIA: All
      patients 18 years of age or older who present to a recruiting hospital for
      treatment of knee pain will be eligible for participation. The subjects must be
      able to understand and complete the questionnaire. EXCLUSION CRITERIA: Patients
      with total knee replacement, open wound or evidence of recent surgery, or with a
      current or a history of tumor and/or fracture in the tibial plateau, femoral
      condyle or patella, in the affected knee are not eligible. STUDY OUTCOMES: This
      study aims to characterize the following: general demographics of patients
      presenting with knee pain, severity of knee symptoms at time of presentation,
      severity of knee pathology at time of presentation, factors associated with the
      decision to seek medical care, previous treatments and health care contacts,
      planned treatment, and gaps in treatment perceived by the patient and treating
      surgeons.

PMID- 24579854
TI  - Conservative treatments, surgical treatments, and the KineSpring(r) Knee Implant
      system for knee osteoarthritis: a systematic review.
AB  - PURPOSE: Knee osteoarthritis (OA) is a disease with a high global burden, and
      multiple treatment options are available. In the current review we summarize the
      results of studies that have evaluated treatments of knee OA, and we compare
      these results with an implantable load absorber called the KineSpring(r) Knee
      Implant System. METHODS: We conducted a literature search of systematic reviews
      on treatment strategies for knee OA. We pooled results for each treatment in
      three categories: pain, function, and stiffness. Then we compared this data to
      that available for the KineSpring System. RESULTS: Medications and
      viscosupplementation show promising initial pain relief for knee OA. Aerobic and
      resistance training, unicompartmental knee arthroplasty (UKA), and total knee
      arthroplasty (TKA) showed a reduction in pain scores. High tibial osteotomy (HTO)
      generally improves pain and function at 6 weeks, but long-term results are
      lacking. The KineSpring System demonstrated significant improvements from
      baseline to 24 months, but direct comparative data are lacking. CONCLUSIONS:
      Evidence for knee OA therapies suggests improved pain, stiffness, and functional
      outcomes. Additional research is necessary to clearly delineate the advantages of
      various approaches to guide practice.

PMID- 24579855
TI  - Viscosupplementation for knee osteoarthritis: current evidence and
      recommendations.
AB  - Osteoarthritis (OA) is the most common joint disorder worldwide and is a leading
      cause of pain and disability. Appropriate management of younger patients with
      milder disease remains a challenging area of intense research.
      Viscosupplementation attempts to restore the biomechanical and biochemical
      functions of normal synovial fluid hyaluronic acid. Several preparations with
      varying characteristics are currently available. The literature suggests a small
      benefit and relative safety, but several recent large meta-analyses have reported
      conflicting results. Major clinical guidelines provide inconclusive
      recommendations. Viscosupplementation may be a viable option in younger patients
      with milder OA where other non-operative modalities are also only modestly
      successful, but further investigation is clearly warranted. Limitations due to
      study heterogeneity, outcome reporting, and bias can each be addressed with
      improved research methodology. 

PMID- 24579856
TI  - Prospective, multi-center, pilot study to evaluate symptom relief in patients
      with medial knee osteoarthritis (OA) treated with the KineSpring(r) knee implant
      for load reduction - the SOAR protocol.
AB  - The study described here is designed as a prospective, multicenter, open-label,
      single-arm pilot study. Eligible subjects with symptomatic osteoarthritis of the
      medial compartment of the knee will be enrolled in the study and will receive the
      KineSpring(r) Knee Implant System. The study population will consist of adult
      patients between 25 and 80 years of age that have been diagnosed with medial knee
      osteoarthritis and have failed to improve after at least 6 months of conservative
      medical treatment. A patient is considered to have a clinically important change
      in OA pain and function with a minimum improvement of 20% compared to baseline
      measures. We will collect data on the safety and effectiveness of the KineSpring
      in patients with primarily unicompartmental medial knee osteoarthritis through 24
      months of postoperative follow-up. These data will provide insights on the
      overall clinical success and safety outcome of KineSpring System. 

PMID- 24579857
TI  - Treatment preferences of patients with early knee osteoarthritis: a decision
      board analysis assessing high tibial osteotomy versus the KineSpring(r) Knee
      Implant System.
AB  - INTRODUCTION: Decision boards can be useful in shared decision making by helping
      patients and their physicians choose among treatment options. Two surgical
      treatments for early knee osteoarthritis (OA) are high tibial osteotomy (HTO) and
      the KineSpring(r) Knee Implant System. The primary objective of this study was to
      determine patient preferences between these two treatments using a decision
      board. METHODS: We developed a decision board that presented information on HTO
      and the KineSpring System for treating knee OA. First, it was presented to 15
      individuals for a pilot test and a "scope test." Then it was presented to 81
      individuals who were asked to imagine that they had early to midstage knee OA,
      and this group was administered a complete a series of questions, including their
      treatment preference and what they would be willing to pay if they elected to use
      the KineSpring System. Descriptive statistics were calculated and a chi-squared
      test was conducted to assess any significant differences in patient preferences
      based on demographic characteristics. RESULTS: Our pilot test confirmed that most
      participants (87%) agreed that the decision board was easy to understand and
      helped them in making a decision. Of 81 respondents, the KineSpring System was
      preferred by 60% (n = 49). Individuals selecting KineSpring would be willing to
      pay an average of $2,700 to receive it over HTO. CONCLUSIONS: When provided with
      treatment options and information, 60% of individuals preferred the KineSpring
      System over HTO. The decision board was well-received as a useful tool for
      presenting information.

PMID- 24579858
TI  - Cost-effectiveness of unicompartmental knee arthroplasty, high tibial osteotomy,
      and KineSpring(r) Knee Implant System for unicompartmental osteoarthritis of the
      knee.
AB  - Osteoarthritis (OA) of the knee is a condition that causes pain and disability.
      Numerous non-surgical and surgical interventions are available for individuals
      with OA that result in good pain relief and return of function. The purpose of
      this economic analysis was to determine the cost-effectiveness of high tibial
      osteotomy (HTO), unicompartmental knee arthroplasty (UKA) and the KineSpring(r)
      Knee Implant System in the treatment of unicompartmental OA of the knee 10 years
      post-surgery, considering the costs of revisions, conversions, removals, and
      complications. Estimates of costs and rates of revision, conversion, removal, and
      complications related to UKA and HTO were obtained from the literature. Internal
      reports on the KineSpring System were used for calculations on the KineSpring
      System. The cost-effectiveness of UKA, HTO and the KineSpring System in terms of
      QALY gained compared to patients without treatment yielded gains of approximately
      $5150/QALY, $6754/QALY, and $7010/QALY, respectively. Using the accepted standard
      willingness-to-pay threshold of $50,000 US/QALY gained, the UKA, HTO, and the
      KineSpring System are economically favorable. Our analysis demonstrates that the
      KineSpring System, despite a greater initial cost in surgery, has significantly
      smaller conversion and complication costs compared to UKA and HTO. The 10 years
      overall expected cost for the KineSpring System ($12,559) is significantly less
      compared with that of UKA ($17,570) and HTO ($22,825). Future economic analyses
      regarding this topic should also consider the cost-effectiveness of these
      procedures on younger, more active individuals who are still working and should
      take into account productivity loss. 

PMID- 24579859
TI  - Cost-effectiveness and economic impact of the KineSpring(r) Knee Implant System
      in the treatment of knee osteoarthritis in the United Kingdom.
AB  - BACKGROUND: Knee osteoarthritis (OA) is a condition affecting 8.5 million
      individuals in the United Kingdom (UK). Although many treatment options are
      available, there is a need for a less-invasive treatment for individuals with
      mild to moderate knee OA. The purpose of the present study was to determine
      whether the KineSpring System is a more effective treatment for knee OA when
      compared to other standard treatments, taking into consideration cost-utility
      ratios. METHODS: Data was collected for the UK population breakdown. A literature
      search provided data on conservative and surgical treatment costs and functional
      outcome scores. The KineSpring System outcome scores were obtained from two
      trials. Quality-adjusted life years (QALYs) gained and cost-utility ratios were
      calculated for each treatment option, assuming a lifetime durability as well as
      10-year durability. RESULTS: Assuming lifetime durability, the cost-utility
      ratios of surgical treatment, total knee arthroplasty (TKA), the KineSpring
      System, and conservative treatments, compared to no treatment are L1,303+/
      22/QALY, L821+/-175/QALY, L796+/-73/QALY and L11,096+/-1188/QALY, respectively.
      Assuming a treatment durability of 10 years, the cost-utility ratio of surgical
      treatment, TKA, the KineSpring System, and conservative treatments, compared to
      no treatment are L4,153+/-95 per QALY, L2,698+/-768 per QALY, L2,848+/-345 per
      QALY, and L10,624+/-1528 per QALY, respectively. CONCLUSION: This study
      demonstrates that the KineSpring System is a cost-effective treatment for knee OA
      and is comparable to current standard-of-care treatments. Further research is
      needed to assess the long-term outcomes associated with the KineSpring System.

PMID- 24579860
TI  - Cost-effectiveness and economic impact of the KineSpring(r) Knee Implant System
      in the treatment of knee osteoarthritis in Italy.
AB  - PURPOSE: The purpose of the present study was to determine whether the KineSpring
      System is a more effective treatment for knee OA when compared to other standard
      treatments, considering cost-utility ratios. METHODS: A literature search
      provided data on conservative and surgical treatment costs and functional outcome
      scores. The KineSpring System outcome scores were obtained from two trials.
      Quality adjusted life years (QALYs) and cost-utility ratios were calculated for
      each treatment option assuming a lifetime durability as well as 10-year
      durability. RESULTS: Assuming lifetime durability, the cost-utility ratios of
      total knee arthroplasty (TKA), unicompartmental knee arthroplasty (UKA), high
      tibial osteotomy (HTO), the KineSpring System, and conservative treatments,
      compared to no treatment were ?2348+/-70 per QALY, ?2040+/-61 per QALY, ?2281 +/-
      68 per QALY, ?1669+/-268 per QALY, and ?11,688+/-2185 per QALY, respectively.
      Assuming a treatment durability of 10 years, the cost-utility ratio of TKA, UKA,
      HTO, the KineSpring System and conservative treatments, compared to no treatment
      were ?4,884+/-323 per QALY, ?4243+/-280 per QALY, ?4,744 +/-313 per QALY, ?3757+/
      1353 per QALY, and ?10,575+/-4414 per QALY, respectively. CONCLUSION: Compared to
      current standard-of-care treatments, the KineSpring System has a favorable cost
      utility ratio, making it an effective treatment option and a suitable cost-saving
      alternative. The KineSpring System is associated with lower cost and increased
      QALYs. Future research is needed to further examine the long-term outcomes
      associated with the KineSpring System.

PMID- 24579861
TI  - Is the treatment gap in knee osteoarthritis real? A qualitative study of
      surgeons' perceptions.
AB  - BACKGROUND: Knee osteoarthritis (OA) is a chronic condition characterized by loss
      of joint cartilage that leads to persistent pain, loss of function, and
      disability. It has been reported that a treatment gap exists in a subset of knee
      OA patients who are unresponsive to conservative treatment yet are unsuitable for
      or unwilling to undergo more invasive, irreversible, surgical procedures.
      METHODS: Ten orthopedic healthcare professionals participated in a focus group
      (n=5) and semistructured interviews (n=5). We explored their perceptions on the
      treatment gap in knee OA patients and their opinions of the KineSpring(r) Knee
      Implant System. RESULTS: Among the responses of orthopedic healthcare
      professionals, we identified seven themes: (1) Delaying operative treatment for
      knee OA patients is very important. (2) Unrealistic expectations of younger
      patients play an important role in management of knee OA. (3) A treatment gap
      does exist. (4) Management of knee OA should be tailored to the individual
      patient. (5) The ability to delay total knee replacement without compromising the
      ability to do it in the future is important for the acceptance of the KineSpring
      System. (6) Improving patient lives by decreasing pain, improving function, and
      potentially delaying arthroplasty is important. (7) A well-designed randomized
      control trial and further evidence regarding the KineSpring System is desired.
      CONCLUSIONS: Orthopedic healthcare professionals are enthusiastic about the
      prospect of the KineSpring System as an option to help close the treatment gap in
      knee OA. Focusing only on clinical trials with long-term data may be impractical
      and deprive patients and society of benefits that can be gained while trial data
      are maturing.

PMID- 24579862
TI  - Challenges in conducting multicenter, multicultural, and multilingual trials: a
      view from the literature and real-life experience reports.
AB  - A trend toward international multicenter clinical trials in the medical device
      industry is helping to increase recruitment figures and to improve the
      generalizability of results, among other factors. However, working globally
      creates its own unique set of problems, which are rarely discussed in the
      literature. This article considers these issues from multicenter, multicultural,
      and multilingual perspectives. A multicenter study implies a replication of work
      to coordinate research sites that are working under different regulations.
      Standardizing elements of the clinical trial is essential for proper comparison
      of results. Multicultural differences manifest themselves in different forms in
      international clinical research. However, the impact of culture on a study's
      success is a real issue, particularly when patient-reported outcomes form part of
      the trial. A trial that is conducted globally obviously requires the use of local
      language material, but this element is fraught with the possibility of
      mistranslation and misunderstanding. In this article, we also examine the
      composition of a research team and how to keep everyone involved in a global
      clinical trial both informed and enthused about a trial that may last several
      years. Examples from our own clinical investigations are reported throughout this
      article. 

PMID- 24579863
TI  - Evaluating implants in orthopaedic trials: tips for conducting research.
AB  - The availability of quality research on orthopaedic implants is important for
      orthopaedic clinical practice, though in many cases such research is deficient in
      the literature. Randomized trials are dwarfed in number by observational studies
      which, though also valuable, do not provide the same validity of evidence. This
      is partly due to the unique challenges faced by orthopaedic clinicians when
      attempting to conduct randomized trials in areas such as randomization, blinding,
      and follow-up. These challenges can be addressed with the use of techniques such
      as expertise-based randomization, assessment that is objective and independent,
      and implementation of a protocol for consistent follow-up before the study is
      underway. Although they do not eliminate all of the hurdles faced in implant
      evaluation trials, the tips outlined in this article have the potential to
      significantly ease the burdens of conducting high-quality research. 

PMID- 24579864
TI  - Knee osteoarthritis prevalence in hospitalized elderly patients: a retrospective
      study.
AB  - This study aimed to determine the prevalence rate of knee osteoarthritis (OA) and
      the risk factors for OA in hospitalized elderly patients. We conducted this
      retrospective study in elderly patients (aged 65 years and older) who were
      hospitalized in the Geriatric Ward of General Hospital of Guangzhou Military
      Command of the People's Liberation Army between January 2011 and June 2013,
      including general condition, present history, past history, physical examination,
      X-ray results, and disease diagnosis. The prevalence, awareness, and treatment
      rates of knee OA in hospitalized elderly patients were calculated. Risk factors
      were computed using multiple logistic regression analysis. Of a total of 267
      (17.4%) hospitalized elderly patients diagnosed with knee OA, the prevalence rate
      of OA was 9.95% in males and 37.76% in females. The rate of awareness among those
      with OA was 51.68%; the rate of treatment was 83.33%; and the rate of control was
      77.39%. The medical expenses for both females (1143+/-315 yuan month-1) and males
      (1192+/-357 yuan month-1) in knee OA patients are higher than that of the non
      knee OA group (989+/-274 yuan month-1, 1038+/-295 yuan month-1). The risk factors
      for knee OA include gender (OR=2.448), age (OR=1.124), transportation mode (OR=
      8.972), exercise (OR=7.374), bowel evacuation position (OR=5.767), family history
      of knee OA (OR=2.195), and body mass index (OR=2.469). The prevalence of knee OA
      is unexpectedly high in hospitalized elderly patients, and the rates of awareness
      and treatment are less than desirable. Prevention and control measures should be
      taken in patients with concomitant risk factors. 

PMID- 24579865
TI  - Preface: joint preservation options in patients with knee osteoarthritis:
      bridging the chasm.

PMID- 24579866
TI  - Psoriasis associated with idiopathic CD4+ T-cell lymphopenia: a regulatory T-cell
      defect?
AB  - Idiopathic CD4(+) lymphocytopenia (ICL) is a rare immunodeficiency syndrome of
      unknown origin for which the increased risks of opportunistic infections and of
      malignancies have been well established; however, skin dysimmune diseases,
      including psoriasis, have been scarcely reported up to now. We report herein the
      severe course of psoriasis in four patients with ICL, and show evidence for a
      defect in the skin recruitment of regulatory CD4(+) FoxP3(+) T cells. These data
      raise the apparent paradigm of the occurrence of a severe immunomediated disease
      together with a profound T-cell defect, a model that might also apply to other
      immune deficiencies associated with psoriasis.

PMID- 24579867
TI  - In-Tube Extraction-GC-MS as a High-Capacity Enrichment Technique for the Analysis
      of Alcoholic Beverages.
AB  - An in-tube extraction (ITEX) method for the GC-MS analysis of volatile
      constituents of alcoholic beverages was developed and applied in the analysis of
      46 beers from six varieties, Alt, Helles, Kolsch, Pilsener beer, Schwarzbier, and
      wheat beer, which are popular in Germany. The extraction performance of nine
      different sorbent materials was evaluated. The best overall sensitivity was
      achieved using Tenax TA, with method detection limits down to 0.01 MUg L-1,
      whereas the widest linear range was possible with PDMS, covering almost 5 orders
      of magnitude. This is the first application of PDMS in ITEX as a high-capacity
      extraction device and highlights the importance of choosing the appropriate
      sorbent material for the analytical task at hand. A satisfying chemometric
      discrimination of all analyzed beer varieties was possible, and alcohol-free
      beers could clearly be separated from regular beers, also.

PMID- 24579868
TI  - Exposure of iron nanoparticles to Arabidopsis thaliana enhances root elongation
      by triggering cell wall loosening.
AB  - In this study, we investigated the effect of nZVI on plant root elongation in
      Arabidopsis thaliana and showed, for the first time, that nZVI enhanced root
      elongation by inducing OH radical-induced cell wall loosening. Exposure of plants
      to 0.5 g/L nZVI enhanced root elongation by 150-200% over that in the control,
      and further mechanistic studies showed that this occurred via nZVI-mediated OH
      radical-induced cell wall loosening. The oxidation capacity of nZVI, leading to
      release of H2O2, allowed it to cause OH radical-induced cell wall loosening in
      roots. Matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometers (MALDI-TOFMS)-based analysis clearly revealed that pectin
      polysaccharides in roots were degraded; they are one of the main matrix
      polysaccharide-connecting and load-bearing polymers in cell walls. Rapid root
      elongation led to structural changes in root cell walls: reduction of cell wall
      thickness and a bias on the orientation of cellulose microfibrils. Additionally,
      the asymmetrical distribution of tensional strength resulted from the OH radical
      induced cell wall loosening enhanced endocytosis. These findings emphasize that
      OH radical-induced cell wall loosening is important for mechanical regulation of
      the cell wall and provide new insights into the cellular responses of plants
      exposed to reactive metal nanoparticles. 

PMID- 24579869
TI  - A strongly CD34-positive meningioma that was difficult to distinguish from a
      solitary fibrous tumor.
AB  - Fibrous or transitional meningioma and solitary fibrous tumor (SFT) are
      frequently difficult to differentiate from each other on the basis of
      histopathology. It is extremely unusual for a meningioma to exhibit diffuse,
      strongly positive immunoreactivity for cluster of differentiation 34 (CD34), and
      this has never been previously reported from a histopathological specimen. A
      patient with transitional meningioma that exhibited strongly positive for CD34,
      which has been regarded as characteristic of SFT and is considered to be useful
      for distinguishing the latter from meningioma, is reported.

PMID- 24579870
TI  - Residents' perceptions about surrogate decision makers' financial conflicts of
      interest in ventilator withdrawal.
AB  - PURPOSE: There have been no studies to date that examine physicians' decisions to
      withdraw life-sustaining treatment for patients based on their surrogates'
      financial gain. The authors' objective was to ascertain physician attitudes about
      withdrawing life-sustaining treatment when financial considerations are involved.
      METHODS: A survey was developed and pretested containing eight scenarios in which
      a terminally ill patient's spouse had a decision to make regarding withdrawal of
      the ventilator, which was deemed medically futile. Nested variables included
      agreement or disagreement between the spouse and patient, decision to withdraw or
      continue the ventilator, and financial gain or no financial gain for the spouse.
      The authors surveyed all internal medicine residents at the University of
      California, San Diego in the autumn of 2011 and winter of 2012. The responses on
      each of the three variables for which respondents were likely to withdraw the
      ventilator were analyzed via student's t-tests. RESULTS: Residents were more
      likely to withdraw the ventilator when requested to do so than when it was
      requested to be continued. They were also more likely to withdraw the ventilator
      when there was agreement in the decision between the spouse and the patient.
      Residents were more likely to withdraw the ventilator when the spouse would not
      benefit financially. CONCLUSIONS: Internal medicine residents make some decisions
      about whether to withdraw life-sustaining treatment based on financial
      considerations. There needs to be ongoing communication with residents about end
      of-life decisions where conflicts may exist between the surrogate decision makers
      and patients or physicians.

PMID- 24579871
TI  - RNA- and antibody-based profiling of the human proteome with focus on chromosome
      19.
AB  - An important part of the Human Proteome Project is to characterize the protein
      complement of the genome with antibody-based profiling. Within the framework of
      this effort, a new version 12 of the Human Protein Atlas ( www.proteinatlas.org )
      has been launched, including transcriptomics data for 27 tissues and 44 cell
      lines to complement the protein expression data from antibody-based profiling.
      Besides the extensive addition of transcriptomics data, the Human Protein Atlas
      now contains antibody-based protein profiles for 82% of the 20 329 putative
      protein-coding genes. The comprehensive data resulting from RNA-seq analysis and
      antibody-based profiling performed within the Human Protein Atlas as well as
      information from UniProt were used to generate evidence summary scores for each
      of the 20 329 genes, of which 94% now have experimental evidence at least at
      transcript level. The evidence scores for all individual genes are displayed with
      regards to both RNA- and antibody-based protein profiles, including chromosome
      centric visualizations. An analysis of the human chromosome 19 shows that ~43% of
      the genes are expressed at the transcript level in all 27 tissues analyzed,
      suggesting a "house-keeping" function, while 12% of the genes show a more tissue
      specific pattern with enriched expression in one of the analyzed tissues only. 

PMID- 24579872
TI  - Influence of amino acid stereocenters on the formation of bicyclic N,O-acetals.
AB  - In recent years, our group has reported the highly diastereoselective acid
      catalyzed N,O-acetalization/intramolecular transcarbamoylation cascade of
      reactions between protected alpha-amino acid derivatives (Ser and Thr) and
      tetramethoxyalkanes. The resulting oligocyclic N,O-acetals have been used as
      excellent chiral building blocks for asymmetric transformations such as
      diastereoselective alkylation of the alpha-position. We now evaluate the scope of
      the reaction with related non-natural alpha-amino acid derivatives. A combined
      experimental and theoretical study reveals the key influence of the alpha-carbon
      substitution (serine versus alpha-methylserine) and the relative configuration of
      alpha-/beta-carbons (threonine versus allo-threonine) in the thermodynamic
      stability of the products and, as a consequence, the stereochemical outcome of
      the reaction. Notably, the complete diastereoselectivity achieved with natural
      amino acid precursors is completely lost with their non-natural analogues. 

PMID- 24579873
TI  - Rhodobacter sphaeroides adaptation to high concentrations of cobalt ions requires
      energetic metabolism changes.
AB  - Rhodobacter sphaeroides has for a long time been investigated for its adaptive
      capacities to different environmental and nutritional conditions, including
      presence of heavy metals, which make it a valuable model organism for
      understanding bacterial adaptation to metal stress conditions and future
      environmental applications, such as bioremediation of polluted sites. To further
      characterize the capability of R. sphaeroides to cope with high cobalt ion
      concentrations, we combined the selection of adaptive defective mutants, carried
      out by negative selection of transposon insertional libraries on 5 mM Co(2+) 
      enriched solid medium, with the analysis of growing capacities and transcriptome
      profiling of a selected mutant (R95). A comparative analysis of results from the
      mutant and wild-type strains clearly indicated that the adaptive ability of R.
      sphaeroides strongly relies on its ability to exploit any available energy
      supplying metabolisms, being able to behave as photo- or chemotrophic
      microorganism. The selected R95 mutant, indeed, exhibits a severe down-expression
      of an ABC sugar transporter, which results nonpermissive for its growth in cobalt
      enriched media under aerobic conditions. Interestingly, the defective expression
      of the transporter does not have dramatic effects on the growth ability of the
      mutant when cultivated under photosynthetic conditions.

PMID- 24579875
TI  - Evaluation of the Safety and Biodistribution of M032, an Attenuated HSV-1 Virus
      Expressing hIL-12, After Intracerebral Administration to Aotus Non-Human
      Primates.
AB  - Herpes simplex virus type 1 (HSV-1) mutants lacking the gamma134.5 neurovirulence
      loci are promising agents for treating malignant glioma. Arming oncolytic HSV-1
      (oHSV) to express immunostimulatory genes may potentiate therapeutic efficacy. We
      have previously demonstrated improved pre-clinical efficacy, biodistribution, and
      safety of M002, a gamma134.5-deleted HSV-1 engineered to express murine IL-12.
      Herein, we describe the safety and biodistribution of M032, a gamma134.5-deleted
      HSV-1 virus that expresses human IL-12 after intracerebral administration to non
      human primates (NHPs), Aotus nancymae. Cohorts were administered vehicle, 106, or
      108 pfu of M032 on Day 1 and subjected to detailed clinical observations
      performed serially over a 92-day trial. Animals were sacrificed on Days 3, 31,
      and 91 for detailed histopathologic assessments of all organs and to isolate and
      quantify virus in all organs. With the possible exception of one animal
      euthanized on Day 16, neither adverse clinical signs nor sex- or dose-related
      differences were attributed to M032. Elevated white blood cell and neutrophil
      counts were observed in virus-injected groups on Day 3, but no other significant
      changes were noted in clinical chemistry or coagulation parameters. Minimal to
      mild inflammation and fibrosis detected, primarily in meningeal tissues, in M032
      injected animals on Days 3 and 31had mostly resolved by Day 91. The highest viral
      DNA levels were detected at the injection site and motor cortex on Day 3 but
      decreased in CNS tissues over time. These data demonstrate the requisite safety
      of intracerebral M032 administration for consideration as a therapeutic for
      treating malignant brain tumors.

PMID- 24579874
TI  - Histologically proven non-alcoholic fatty liver disease and clinically related
      factors in recipients after liver transplantation.
AB  - Non-alcoholic fatty liver disease (NAFLD) affects a substantial proportion of the
      world population, and its prevalence has been increasing. The study was aimed at
      evaluating the prevalence and peri-transplant risk factors for post-liver
      transplantation (LT) NAFLD. A retrospective review was performed for adult
      recipients who underwent late protocol biopsy (>1 yr after LT) between August
      2010 and December 2012. Hepatic steatosis was reviewed and graded by
      hepatopathologists, and the peri-transplant factors were analyzed for
      relationships to histologically proven NAFLD. Total 166 biopsies had been
      performed in 156 recipients. NAFLD was present in 27.1% at a mean period of 35.4
      months between LT and biopsy, moderate and severe steatosis (>=33%) consisted of
      28.9%. In multivariate analysis, pre-LT alcoholic cirrhosis (odds ratio [OR]
      8.031, p = 0.003), obesity at biopsy (OR 3.873, p = 0.001), and preexisting donor
      graft steatosis (OR 3.147, p = 0.022) were significant risk factors for post-LT
      NAFLD. In conclusion, NAFLD represented a considerable portion of recipients, but
      this prevalence was not higher than those for general population. Three risk
      factors were significantly related to post-LT NAFLD, and recipients with those
      factors should be monitored for NAFLD. Furthermore, possible progression to non
      alcoholic steatohepatitis (NASH) or fibrosis and metabolic syndrome should be
      considered in future studies.

PMID- 24579876
TI  - Neuropsychological examination detects post-operative complications in idiopathic
      normal pressure hydrocephalus (iNPH): report of two cases.
AB  - Subdural fluid collections (SFC) are characteristic complications of shunting for
      idiopathic normal pressure hydrocephalus (iNPH). This report presents two shunted
      iNPH patients with clinically silent postoperative SFC, detected after abnormal
      neuropsychological findings. These cases highlight the value of
      neuropsychological assessment in the routine postoperative assessment of iNPH. 

PMID- 24579877
TI  - Load sharing in lumbar spinal segment as a function of location of center of
      rotation.
AB  - OBJECT: The center (axis) of rotation (COR) in the lumbar spine has been studied
      well. However, there is limited information on the kinetic and kinematic
      consequences of imposed shift in the location of the COR, although this type of
      shift can be seen after surgeries using motion preservation or dynamic
      stabilization devices. The objective of this study was to assess the kinetic and
      kinematic changes in the lumbar spinal segment due to various imposed CORs.
      METHODS: A 3D finite element model of the L4-5 segment was constructed and
      validated. The segment was loaded under a 7.5-Nm bending moment while constrained
      to rotate about various imposed CORs in the sagittal and axial motion planes.
      Range of motion, ligament forces, facet loads, and disc stresses were measured.
      RESULTS: The present model showed an agreement with previous in vitro and finite
      element studies under the same load and boundary conditions. Range of motion,
      facet forces, disc stresses, and ligament loads showed a strong association with
      the location of the COR. CONCLUSIONS: Acute alterations in the location of the
      COR can significantly change the load sharing characteristics within the spine
      segment. The normal location of the COR is a result of the tendency of the
      vertebra to move in the path of least cumulative resistance.

PMID- 24579878
TI  - Stimulus type and the list strength paradigm.
AB  - In recognition memory, increasing the strength of studied items does not reduce
      performance on other items, an effect dubbed the null list strength effect (LSE).
      While this finding has been replicated many times, it has rarely been tested
      using stimuli other than single words. Kinnell and Dennis ( 2012 ) recently
      tested for the presence of list length effects using non-word stimulus classes
      while controlling for the confounds that are present in list length designs.
      Small list length effects were found for fractal and face images. We adopted the
      same paradigm and stimuli used by Kinnell and Dennis to test whether these
      stimuli would be susceptible to list strength effects as well. We found
      significant LSEs for fractal images, but null LSEs for face images and natural
      scene photographs. Stimuli other than words do appear to be susceptible to list
      strength effects, but these effects are small and restricted to particular
      stimulus classes, as is the case in list length designs. Models of memory may be
      able to address differences between these stimulus classes by attributing
      differences in representational overlap between the stimulus classes. 

PMID- 24579879
TI  - Biological activities of organic extracts of four Aureobasidium pullulans
      varieties isolated from extreme marine and terrestrial habitats.
AB  - We report on the screening for biological activities of organic extracts from
      seven strains that represent four varieties of the fungus Aureobasidium
      pullulans, that is A. pullulans var. melanogenum, A. pullulans var. pullulans, A.
      pullulans var. subglaciale and A. pullulans var. namibiae. We monitored
      haemolysis, cytotoxicity, antioxidant capacity and growth inhibition against
      three bacterial species. The haemolytic activity of A. pullulans var. pullulans
      EXF-150 strain was due to five different haemolytically active fractions.
      Extracts from all of the other varieties contained at least one haemolytically
      active fraction. Short-term exposure of cell lines to these haemolytically active
      organic extracts resulted in more than 95% cytotoxicity. Strong antioxidant
      capacity, corresponding to 163.88 MUg ascorbic acid equivalent per gram of total
      solid, was measured in the organic extract of the strain EXF-3382, obtained from
      A. pullulans var. melanogenum, isolated from the deep sea. Organic extracts from
      selected varieties of A. pullulans exhibited weak antibacterial activities.

PMID- 24579880
TI  - Manipulating crystallization with molecular additives.
AB  - Given the importance of organic crystals in a wide range of industrial
      applications, the chemistry, biology, materials science, and chemical engineering
      communities have focused considerable attention on developing methods to control
      crystal structure, size, shape, and orientation. Tailored additives have been
      used to control crystallization to great effect, presumably by selectively
      binding to particular crystallographic surfaces and sites. However, substantial
      knowledge gaps still exist in the fundamental mechanisms that govern the
      formation and growth of organic crystals in both the absence and presence of
      additives. In this review, we highlight research discoveries that reveal the role
      of additives, either introduced by design or present adventitiously, on various
      stages of formation and growth of organic crystals, including nucleation,
      dislocation spiral growth mechanisms, growth inhibition, and nonclassical crystal
      morphologies. The insights from these investigations and others of their kind are
      likely to guide the development of innovative methods to manipulate
      crystallization for a wide range of materials and applications. 

PMID- 24579881
TI  - Exome sequencing identifies a de novo SCN2A mutation in a patient with
      intractable seizures, severe intellectual disability, optic atrophy, muscular
      hypotonia, and brain abnormalities.
AB  - Epilepsy is a phenotypically and genetically highly heterogeneous disorder with
      >200 genes linked to inherited forms of the disease. To identify the underlying
      genetic cause in a patient with intractable seizures, optic atrophy, severe
      intellectual disability (ID), brain abnormalities, and muscular hypotonia, we
      performed exome sequencing in a 5-year-old girl and her unaffected parents. In
      the patient, we detected a novel, de novo missense mutation in the SCN2A
      (c.5645G>T; p.R1882L) gene encoding the alphaII -subunit of the voltage-gated
      sodium channel Nav 1.2. A literature review revealed 33 different SCN2A mutations
      in 14 families with benign forms of epilepsy and in 21 cases with severe
      phenotypes. Although almost all benign mutations were inherited, the majority of
      severe mutations occurred de novo. Of interest, de novo SCN2A mutations have also
      been reported in five patients without seizures but with ID (n = 3) and/or autism
      (n = 3). In the present study, we successfully used exome sequencing to detect a
      de novo mutation in a genetically heterogeneous disorder with epilepsy and ID.
      Using this approach, we expand the phenotypic spectrum of SCN2A mutations. Our
      own and literature data indicate that SCN2A-linked severe phenotypes are more
      likely to be caused by de novo mutations. A PowerPoint slide summarizing this
      article is available for download in the Supporting Information section here. 

PMID- 24579882
TI  - The need for global collaboration to tackle hidden public health crisis of Chagas
      disease.
AB  - Chagas disease has a unique history where the confluence of rural and
      marginalized populations affected, the deeply rooted attitudes, clinical
      practices and an underfunded research area has resulted in one of the most
      current neglected health issues. Globalization has changed the epidemiology of
      the disease, which is now found throughout the Americas but also in Europe and
      Japan. Thus, Chagas disease is a global public health problem. In this new
      paradigm, a strong partnership aimed to coordinate actions to scale up
      diagnostics and treatments, to engage communities and health practitioners in
      implementation and advocating for sustained funding for the development of
      improved tools, can play a critical role to leave behind this story of neglect.
      Even with the imperfect tools currently available, still much can be done. 

PMID- 24579883
TI  - Bilayer mucoadhesive microparticles for the delivery of metoprolol succinate:
      Formulation and evaluation.
AB  - Metoprolol succinate is a very potent drug for the treatment of hypertension but
      suffers from poor bioavailability due to its erratic absorption in lower GI
      tract. Therefore, in the present study, it was hypothesized that by formulating
      mucoadhesive particles, the residence time in the GIT and release of drug may be
      prolonged that will enhance the bioavailability of metoprolol succinate.
      Metoprolol succinate loaded chitosan microparticles were prepared by ionic
      gelation method. The optimized microparticles were coated with sodium alginate to
      form a layer over chitosan microparticles to increase the mucoadhesive strength
      and to release the drug in controlled manner. Coated and uncoated microparticles
      were evaluated for particle size, zeta potential, morphology, entrapment
      efficiency, drug loading and in vitro drug release. The coated microparticles
      showed comparatively less drug release in the 0.1 N HCl while sustained release
      in PBS (pH 6.8) as compared to uncoated microparticles. The in vivo study on
      albino rats demonstrated an increase in bioavailability of the coated
      microparticles as compared to marketed formulation. From the study it can be
      concluded that alginate coated chitosan microparticles could be a useful carrier
      for the oral delivery of metoprolol succinate. 

PMID- 24579884
TI  - Glucocorticoid metabolism in rheumatoid arthritis.
AB  - Endogenous glucocorticoids are implicated in the development and resolution of
      inflammation. Until recently it was thought that these glucocorticoids arose
      primarily from the adrenal gland. However, it is now known that several cell
      types can generate active glucocorticoids within their cytoplasm through
      expression of the 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1)
      enzyme. In a more limited range of cell types, glucocorticoids can be inactivated
      by the related 11beta-HSD2 enzyme. Both enzymes are regulated by inflammation in
      various settings. In rheumatoid arthritis, 11beta-HSD activity is present in the
      inflamed synovium and appears to influence articular and extraarticular disease
      processes. The generation of active glucocorticoids in the synovium is strongly
      linked to the level of inflammation. This local production of glucocorticoids is
      likely to have paracrine consequences and could underpin inflammation-associated
      bone loss. The role of 11beta-HSD enzymes in the severity and persistence of
      inflammatory arthritis in a clinical setting is currently being explored. 

PMID- 24579887
TI  - Dietary influence on urinary excretion of 3-deoxyglucosone and its metabolite 3
      deoxyfructose.
AB  - 3-Deoxyglucosone (3-DG), a reactive 1,2-dicarbonyl compound derived from d
      glucose in food and in vivo, is an important precursor for advanced glycation
      endproducts (AGEs). At present, virtually no information about the metabolic
      transit of dietary 3-DG is available. One possible metabolic pathway of 3-DG
      during digestion is enzymatic transformation to less reactive compounds such as 3
      deoxyfructose (3-DF). To study the handling of dietary 1,2-dicarbonyl compounds
      by the human body, 24 h urinary excretion of 3-DG and its metabolite, 3
      deoxyfructose, was investigated. Urinary 3-DG and 3-DF excretion was monitored
      for nine healthy volunteers following either a diet with no dietary restrictions
      or a diet avoiding the ingestion of 3-DG and other Maillard reaction products
      ("raw food" diet). During the "raw food" diet, the urinary 3-DG and 3-DF
      excretion decreased approximately to 50% compared to the excretions during the
      diet with no restrictions. When subjects received a single dose of wild honey (50
      g) naturally containing a defined amount of 3-DG (505 MUmol), median excretion of
      3-DG and 3-DF increased significantly from 4.6 and 77 to 7.5 and 147 MUmol/day,
      respectively. The obtained experimental data for the first time demonstrate a
      dietary influence on urinary 3-DG and 3-DF levels in healthy human subjects.

PMID- 24579885
TI  - SWOG S0910: a phase 2 trial of clofarabine/cytarabine/epratuzumab for
      relapsed/refractory acute lymphocytic leukaemia.
AB  - Precursor B-acute lymphoblastic leukaemias (pre-B ALLs) comprise the majority of
      ALLs and virtually all blasts express CD22 in the cytoplasm and on the cell
      surface. In the present study (Southwestern Oncology Group S0910), we evaluated
      the addition of epratuzumab, a humanized monoclonal antibody against CD22, to the
      combination of clofarabine and cytarabine in adults with relapsed/refractory pre
      B ALL. The response rate [complete remission and complete remission with
      incomplete count recovery] was 52%, significantly higher than our previous trial
      with clofarabine/cytarabine alone, where the response rate was 17%. This result
      is encouraging and suggests a potential benefit to adding epratuzumab to
      chemotherapy for ALL; however, a randomized trial will be needed to answer this
      question. 

PMID- 24579886
TI  - Relief of menstrual symptoms and migraine with a single-tablet formulation of
      sumatriptan and naproxen sodium.
AB  - BACKGROUND: Dysmenorrhea and menstrual migraine may share a common pathogenic
      pathway. Both appear to be mediated, in part, by an excess of prostaglandin
      production that occurs during menstruation. METHODS: Data were pooled from two
      replicate randomized controlled trials of 621 adult menstrual migraineurs with
      dysmenorrhea who treated migraine with sumatriptan-naproxen or placebo. Along
      with headache symptoms, nonpain menstrual symptoms (bloating, fatigue, and
      irritability) and menstrual pain symptoms (abdominal and back pain) were recorded
      at the time periods of 30 minutes and 1, 2, 4, and 4-24 hours. Relief of
      menstrual symptoms was compared using a Cochran-Mantel-Haenszel test. Logistic
      regression was used to determine the odds of a headache response with increasing
      numbers of moderate to severe dymenorrheic symptoms. RESULTS: Sumatriptan
      naproxen was superior to placebo for relief of tiredness, irritability, and
      abdominal pain at the time periods of 2, 4, and 4-24 hours (p<=0.023); back pain
      at the time periods of 4 and 4-24 hours (p<=0.023); and bloating at 4-24 hours
      endpoint (p=0.01). The odds ratios (ORs) of attaining migraine pain freedom for 2
      hours and for sustained 2-24 hours decreased as moderate to severe dysmenorrhea
      symptoms increased with sumatriptan-naproxen versus placebo. CONCLUSIONS:
      Treatment with sumatriptan-naproxen may provide relief of menstrual symptoms and
      migraine in female migraineurs with dysmenorrhea. The presence of moderate to
      severe dysmenorrhea symptoms is associated with decreased response rates for
      menstrual migraine, suggesting that the co-occurrence of these disorders may
      negatively impact the results of migraine-abortive therapy.

PMID- 24579888
TI  - The emergence of targeted drugs in breast cancer to prevent resistance to
      endocrine treatment and chemotherapy.
AB  - INTRODUCTION: Deregulated signaling pathways are associated with resistance to
      chemotherapy and endocrine treatment, providing a rationale for the
      implementation of novel targeted therapies in breast cancer therapy. Key
      molecules targeted therapeutically in ongoing clinical breast cancer trials are
      phosphoinositide 3-kinase-Akt-mammalian target of rapamycin (mTOR), Src, insulin
      like growth factor 1 receptor, heat shock protein-90, histone deacetylases,
      cyclin-dependent kinases (CDKs), Notch and human epidermal growth factor
      receptors (HERs). AREAS COVERED: This review provides an overview of novel
      targeted agents currently explored in clinical breast cancer trials and
      registered in ClinicalTrials.gov. The main focus will be on their ability to
      prevent or reverse endocrine resistance and chemoresistance in breast cancer.
      EXPERT OPINION: HER2 targeted agents have extended survival substantially, both
      in the adjuvant and metastatic setting, pointing to a crucial dependency on this
      pathway in HER2-amplified breast cancer, including drug resistance reversal.
      While data on mTOR inhibitors are encouraging and preliminary results on CDK4/6
      and Src inhibitors exciting, so far other targeted agents have been of limited
      benefit when added in concert with conventional therapies. Future clinical trials
      should systematically explore biomarkers and defects in functional gene cascades
      to identify relevant biological mechanisms to be targeted therapeutically in
      breast cancer.

PMID- 24579890
TI  - Activation of monocyte-derived cells in the bone marrow of myelodysplastic
      syndrome.
AB  - OBJECT: To study the relationship between monocyte/histiocyte activation and
      myelodysplastic syndrome (MDS). METHODS: Analyzing ultrastructure and
      myeloperoxidase reaction of nucleated cells in bone marrow from 59 cases of MDS
      by transmission electron microscopy. Four groups of MDS were subdivided on the
      basis of their content of activated inflammatory cells - morbid hematopoiesis
      with minimal inflammatory cell activation (MH-MICA); MDS with monocytic system
      activation (MSA); MDS with lymphocyte activation (LCA); and MDS with granulocyte
      activation (GCA). RESULTS: About 20, 22, 7, and 10 cases were classified as MH
      MICA (34%), MSA (37%), LCA (12%), and GCA sub-types (17%), respectively. About 3,
      5, 0, and 3 cases from MH-MICA, MSA, LCA, and GCA, respectively, underwent
      leukemic transformation within 2 years. CONCLUSION: The findings suggest that
      activation of inflammatory cells in bone marrow is an important feature of MDS,
      and that monocytes/histocytes are perhaps the most prominent cellular
      participants in the pathogenesis of MDS.

PMID- 24579891
TI  - Cultivation and isolation of N2-fixing bacteria from suboxic waters in the Baltic
      Sea.
AB  - Nitrogenase genes (nifH) from heterotrophic dinitrogen (N2)-fixing bacteria
      appear ubiquitous in marine bacterioplankton, but the significance of these
      bacteria for N cycling is unknown. Quantitative data on the N2-fixation potential
      of marine and estuarine heterotrophs are scarce, and the shortage of cultivated
      specimens currently precludes ecophysiological characterization of these
      bacteria. Through the cultivation of diazotrophs from suboxic (1.79 MUmol O2 L(
      1)) Baltic Sea water in an artificial seawater medium devoid of combined N, we
      report the cultivability of a considerable fraction of the diazotrophic community
      in the Gotland Deep. Two nifH clades were present both in situ and in enrichment
      cultures showing gene abundances of up to 4.6 * 10(5) and 5.8 * 10(5) nifH gene
      copies L(-1) within two vertical profiles in the Baltic Sea. The distributions of
      the two clades suggested a relationship with the O2 concentrations in the water
      column as abundances increased in the suboxic and anoxic waters. It was possible
      to cultivate and isolate representatives from one of these prevalent clades, and
      preliminary analysis of their ecophysiology demonstrated growth optima at 0.5-15
      MUmol O2 L(-1) and 186-194 MUmol O2 L(-1) in the absence of combined N.

PMID- 24579892
TI  - Low-copy number protein detection by electrode nanogap-enabled dielectrophoretic
      trapping for surface-enhanced Raman spectroscopy and electronic measurements.
AB  - We report a versatile analysis platform, based on a set of nanogap electrodes,
      for the manipulation and sensing of biomolecules, as demonstrated here for low
      copy number protein detection. An array of Ti nanogap electrode with sub-10 nm
      gap size function as templates for alternating current dielectrophoresis-based
      molecular trapping, hot spots for surface-enhanced Raman spectroscopy as well as
      electronic measurements, and fluorescence imaging. During molecular trapping,
      recorded Raman spectra, conductance measurements across the nanogaps, and
      fluorescence imaging show unambiguously the presence and characteristics of the
      trapped proteins. Our platform opens up a simple way for multifunctional low
      concentration heterogeneous sample analysis without the need for target
      preconcentration. 

PMID- 24579893
TI  - Management of maxillary sinus perforation at the time of immediate implantation
      with sinus-socket osteotomy (SSO) technique.
AB  - Immediate implantation related to socket and vital anatomy of the maxillary sinus
      area requires careful consideration. One major complication that may occur during
      immediate replacement of posterior teeth is maxillary sinus membrane perforation.
      To date, no specific technique has been proposed to manage this problem so that
      implant insertion remains possible during the same surgery. In this paper, we
      introduce a method to manage this type of perforation and while performing
      simultaneous implantation. We used sinus-socket osteotomy (SSO), a modified
      osteotomy technique for socket preparation that blocks sinus perforation with
      autogenous bone. A 12-month follow-up showed that this technique was clinically
      successful and reduced the overall treatment time. However, this advanced method
      requires a skillful surgeon. 

PMID- 24579894
TI  - A study on polyethylene stresses in mobile-bearing and fixed-bearing total knee
      arthroplasty (TKA) using explicit finite element analysis.
AB  - Mobile-bearing total knee arthroplasty designs were thought to be associated with
      lesser stresses on the polyethylene (PE) insert as compared to fixed-bearing
      designs. The wear rate of the PE liner was felt to be less in the mobile-bearing
      knees due to the decrease in the stresses. However, a reevaluation of the
      biomechanics of the mobile-bearing design is necessary due to the recent clinical
      reports on the long-term outcome of mobile-bearing knees which have not
      demonstrated any significant benefit in terms of implant survival and
      polyethylene wear rate. In this explicit finite element analysis of mobile
      bearing and fixed-bearing knee designs using LS-DYNA, no significant differences
      have been found in the maximal stresses in the superior (articulating) surface of
      the PE insert in mobile- and fixed-bearing designs. On the inferior surface of
      the PE insert, the peak stresses were nearly 30% higher in the mobile-bearing
      compared with the fixed-bearing design. Thus, contrary to earlier expectations,
      mobile-bearing designs may be associated with higher overall PE stresses and wear
      than the fixed-bearing designs. Further research is necessary to minimize the
      wear rate of the PE insert in mobile-bearing total knee arthroplasty. 

PMID- 24579895
TI  - Three- to six-year results of metacarpophalangeal joints arthroplasty in
      psoriatic arthritis.
AB  - BACKGROUND: Patients with psoriatic arthritis often need the replacement of the
      hand joints owing to the high prevalence of hand joints involvement and their
      often severe destruction and/or function loss. The long-term results of silicone
      arthroplasty of metacarpophalangeal joints in psoriatic patients are almost
      unreported in the scientific literature. MATERIALS AND METHODS: We analyzed 3- to
      6-year results of 14 metacarpophalangeal joint replacements with silicone
      implants that we performed in nine psoriatic patients. RESULTS: The
      metacarpophalangeal joints arthroplasty in all the patients led to the
      significant short-term and long-term increase of range of motions and decrease of
      pain. However, two complications occurred. The choice of the implant, the
      possibility, causes, and significance of the complications are justified.
      CONCLUSIONS: Metacarpophalangeal joints silicone arthroplasty in psoriatic
      arthritis during skin manifestations remission period is an effective and
      relatively safe method of finger joints contractures and deformities treatment.

PMID- 24579896
TI  - Inheritable risk factors for venous thromboembolism in patients undergoing lower
      extremity total joint arthroplasty.
AB  - Venous thromboembolism is a common and undesirable complication of both total hip
      and knee arthroplasty. The basic biology and major modifiable risk factors
      predisposing to thromboembolism are well established, but a complete
      understanding of the role and management of inherited coagulopathies is lacking.
      In this manuscript, we have attempted to review the fundamental pathophysiology
      of the coagulation cascade, analyze recent literature on heritable coagulopathies
      leading to venous thromboembolism in patients undergoing lower extremity joint
      arthroplasty, and discuss how an understanding of such factors may affect
      clinical practice. We advocate that a sound understanding of inherited
      coagulopathies, as they relate to hip and knee arthroplasty, may help to aid
      decision making regarding prophylaxis which may eventually lead to an established
      algorithm system for screening and managing patients at high risk for adverse
      thromboembolic events. 

PMID- 24579897
TI  - Outcomes of primary total knee arthroplasty in the morbidly obese patients.
AB  - The purpose of this study was to assess the clinical and radiographic outcomes of
      primary total knee arthroplasty (TKA) in morbidly obese patients compared to a
      cohort who had a normal body mass index (BMI). We reviewed 105 knees in 84
      patients who had a minimum BMI of 40 kg/m2 who underwent a primary TKA between
      2006 and 2010. There were 17 men and 67 women who had a mean age of 59 years and
      a mean follow-up of 52 months. Outcomes evaluated included implant survivorship,
      Knee Society scores, activity scores, and complications. Kaplan-Meier analysis
      demonstrated statistically similar overall implant survivorship between the
      morbidly obese and the comparison groups (96 vs 97%). However, the mean Knee
      Society objective (85 vs 91 points) and functional scores (84 vs 89 points), as
      well as activity scores (4.2 vs 6.1 points) were lower and complications were
      higher in morbidly obese patients at final follow-up. It is encouraging that in
      the morbidly obese patients, total knee arthroplasty can have acceptable results
      at midterm follow-up, however, these patients may benefit from preoperative
      counseling to have realistic expectations from their surgery. 

PMID- 24579898
TI  - Early results of total hip arthroplasty in the super-obese patients.
AB  - The purpose of this study was to assess the outcomes of primary total hip
      arthroplasty (THA) in super-obese patients compared to a cohort who had a normal
      body mass index (BMI). Twenty patients (23 hips) who had a minimum BMI of 50
      kg/m2 who underwent a primary THA between 2001 and 2010 were reviewed. They had a
      mean age of 50 years and follow-up of 36 months. These patients were compared
      (1:2 ratio) to a matched group of 40 patients (46 hips) who had a normal body
      mass index (less than 25 kg/m2) who underwent a THA during the same time period.
      Outcomes evaluated included implant survivorship, Harris hip scores, and
      complication rates. Overall, aseptic implant survivorship was lower in the super
      obese patients compared to the matching group (96% versus 100%), but the
      difference was not significant. However, super-obese patients had significantly
      lower mean Harris hip scores (84 vs 91 points) and higher complication rate at
      final follow-up. Although the clinical outcomes of primary total hip arthroplasty
      were poorer in the super-obese patients, it is encouraging that even in these
      patients, total hip arthroplasty can have acceptable outcomes. However, these
      patients may benefit from a discussion with their orthopaedic surgeons to develop
      realistic expectations from the outcomes of their arthroplasty procedure. 

PMID- 24579899
TI  - Patient activity after total hip arthroplasty: a comparison of three different
      bearing surfaces.
AB  - Patients who receive hip arthroplasty today desire prostheses that not only have
      great longevity, but are also suitable for a very active lifestyle. Advances in
      metallurgy, tribologic behavior, surgical technique, as well as improvements in
      strength and microstructure, have made ceramic-on-ceramic and metal-on-metal
      bearings available for young patients requiring a great deal of mobility. The
      purpose of this study was to assess if the bearing surface had an effect, if any,
      on postoperative activity levels and clinical outcomes in patients receiving
      three different types of hip arthroplasty. This study includes three groups of 30
      patients who had each received conventional metal-on-polyethylene total hip
      arthroplasty (THA), ceramic-on-ceramic THA, or hip resurfacing arthroplasty. All
      groups were matched by men to women ratio, age, body mass index, diagnosis,
      preoperative activity levels, and length of follow-up. Clinical outcomes
      evaluated included weighted postoperative activity levels, Harris hip scores,
      patient satisfaction scores, revision rates, and complication rates. Patients who
      had received a metal-on-metal resurfacing had achieved significantly higher
      activity scores (mean 10.5 points; range, 1-28 points) compared to patients who
      had received ceramic-on-ceramic (mean 6.9 points; range, 0-34 points) or metal-on
      polyethylene bearings (mean 5.6 points; range, 1-18 points). The mean
      postoperative Harris hip scores (94 vs 92 vs 91 points), patient satisfaction
      scores (9 vs 8.4 vs 8.3 points), aseptic revision (3% vs 0% vs 0%), and
      complication rates (3% vs 3% vs 3%) were similar between resurfacing, ceramic-on
      ceramic, and metal-on-polyethylene bearing groups, respectively. This study
      showed that in cohorts of similarly matched arthroplasty patients in multiple
      demographics factors and preoperative activity levels, metal-on-metal resurfacing
      arthroplasty may offer higher postoperative activity levels. For patients with
      higher activity levels, resurfacing arthroplasty may be advantageous compared to
      other types of bearings. 

PMID- 24579900
TI  - Treatment of primary hip osteoarthritis for the primary care physician and the
      indications for total hip arthroplasty.
AB  - Osteoarthritis is a degenerative condition that commonly affects knees and hips
      with an annual incidence of 88 in 100,000 people in the United States. The
      purpose of this study was to review the clinical presentation of osteoarthritis
      of the hip as well as the available management options. We reviewed the recent
      literature in regard to epidemiology, presentation, and treatment options
      available to patients. Nonoperative treatments include weight loss and low
      impact, aerobic exercises. Along with weight loss and exercise, nonsteroidal anti
      inflammatory drugs (NSAIDS), narcotics, and intra-articular steroid injections
      have been used to improve patient's symptoms. Surgical intervention is a viable
      option; however, indications such as severe pain that is refractory to
      nonsurgical management, osteophytes, or joint space narrowing on radiographic
      films, or impairment of function should be present. The most common surgical
      option, total hip arthroplasty, has been shown to improve a patient's physical
      and psychological well-being. However, inherent risks are present with surgery
      and these should be addressed with the patient so a sound decision can be made.
      Osteoarthritis of the hip can be bothersome to patients, but physicians can begin
      management with lifestyle changes or pharmaceuticals. In the event nonoperative
      measures fail to markedly improve quality of life, total hip arthroplasty remains
      a viable option. 

PMID- 24579902
TI  - Function related specifications for total knee arthroplasty implant devices.
AB  - Current specifications for total knee implant devices reflect components'
      properties separate from each other and often in noncomparable units. We can
      recognize the tibial base plate thickness, size of femoral component, etc. How
      does it reflect the functional capabilities of the whole assembly, particularly
      in relation to wear and survivorship? Such approach does not take into account
      the fact that the individual components interact with each other, which in turn
      defines the final evaluation. We suggest a new function related approach to
      specifications which will help to develop clinically relevant standardization
      methodology. We propose an Index of Congruence to be added in the future as a
      required specification for implants of all designs. This universal
      standardization will help surgeons in preoperative planning and may also serve as
      a common denominator to enable comparative studies between diverse designs and
      different manufacturers. 

PMID- 24579901
TI  - Patellar fractures following total knee arthroplasty: a review.
AB  - There are several periprosthetic complications associated with total knee
      arthroplasty, with femoral fracture as the most common and patellar fractures as
      the second most common. Patellar fractures are challenging complications that
      occur almost exclusively on the resurfaced patellae, although unresurfaced
      patellar fractures have been reported in literature. The purpose of this study is
      to describe the anatomy of the patella, the etiology of patellar fractures, and
      strategies to treat and manage these fractures following knee arthroplasty. The
      vascular supply to the patella may be compromised during total knee arthroplasty
      and special care must be taken to preserve it. Vessel injury may result in
      further complications, most notably avascular necrosis with subsequent fracture.
      Other patient-, surgical-, and prosthetic-related factors can contribute to
      increased risk of patellar fracture. Patellar fractures are classified into three
      types. Type I fractures have an intact extensor mechanism with a stable implant.
      Type II fractures have a complete disruption of the extensor mechanism with or
      without a stable implant. Type III fractures, which are further subclassified
      into types IIIa and IIIb, have an intact extensor mechanism but a loose patellar
      component. While type IIIa fractures have reasonable remaining bone stock, type
      IIIb fractures have poor bone stock. Type I patellar fractures may be best
      managed nonoperatively, but types II and III patellar fractures often necessitate
      surgical intervention. Patellectomy should be reserved for comminuted fractures,
      as well as fractures in patients with poor bone stock. Larger prospective
      randomized studies are necessary to better evaluate the treatment algorithm for
      patellar fractures following total knee arthroplasty. 

PMID- 24579903
TI  - Absence of tissue ingrowth through the textile fabric in a series of explanted
      clinic stent-grafts.
AB  - Using the retrieved devices from one autopsy and five reoperations, the
      biocompatibility of explanted Talent stent-grafts was investigated to highlight
      the capacity of the fabric to act as an effective scaffold to regenerate a blood
      conduit. The autopsy device was encapsulated both internally and externally, but
      the capsules did not penetrate through the fabric structure. The reoperation
      devices showed discrete patches of compact fibrin and irregularly scattered mural
      thrombi. Positive staining of alpha-actin, tissue plasminogen activator (tPA),
      urokinase (uPA), urokinase receptor (uPAR), and urokinase inhibitors (PAI 1, PAI
      2, PAI 3, and protease nexin), and D-dimer was more frequently identified in the
      autopsy sample than in the reoperation samples. This preliminary assessment shows
      that the stent-graft retrieved during autopsy was better healed than those
      explanted at reoperation. 

PMID- 24579906
TI  - Update of enterovirus 71 infection: epidemiology, pathogenesis and vaccine.
AB  - Enterovirus 71 (EV71) is a neurotropic human pathogen that is the causative agent
      of hand foot and mouth disease (HFMD), herpangina and brain stem encephalitis.
      Recurrent EV71 epidemics of various scales have occurred in the Asia-Pacific
      region. Several specific cell surface molecules serve as the receptors for EV71.
      Identification of the receptors is an important step to understand EV71 disease.
      Cytokines, lymphocytes and monocytes contribute significantly to EV71
      pathogenesis. The interaction of EV71 and receptors may be associated with the
      cytokines immunopathogenesis. Some animal models have been established and aim to
      explore the pathogenesis of EV71 infections. EV71 antibodies can neutralize or
      enhance infection at subneutralizing levels. These results are important for EV71
      vaccine and therapeutics design. Several clinical trials of human inactivated
      EV71 vaccine have recently been completed. The purpose of this review is to
      summarize recent discoveries about the epidemiology and pathogenesis of EV71 and
      provide insights into human vaccine development. 

PMID- 24579904
TI  - Risk of serious gastrointestinal bleeding in living kidney donors.
AB  - Individuals with moderate-to-severe reduced renal function have greater risk of
      gastrointestinal bleeding than those with normal renal function. We conducted a
      retrospective matched cohort study to assess whether living kidney donors share a
      similar risk. We reviewed pre-donation charts for living kidney donations from
      1992 to 2009 in Ontario, Canada, and linked this information to healthcare
      databases. We selected healthy non-donors from the general population and matched
      ten non-donors to every donor. Of the 2009 donors and 20,090 matched non-donors,
      none had evidence of gastrointestinal bleeding prior to cohort entry. The cohort
      was followed for a median of 8.4 yr (maximum 19.7 yr; loss to follow-up <7%).
      There was no significant difference in the rate of hospitalization with
      gastrointestinal bleeding in donors compared to non-donors (18.5 vs. 14.9 events
      per 10,000 person-years; rate ratio 1.24; 95% confidence interval [CI] 0.85
      1.81). Similar results were obtained when we assessed the time to first
      hospitalization with gastrointestinal bleeding (hazard ratio 1.25, 95% CI 0.87
      1.79). In conclusion, we found living kidney donation was not associated with a
      higher risk of hospitalization with gastrointestinal bleeding. These results are
      reassuring for the safety of the practice.

PMID- 24579907
TI  - Monitoring the efficacy of once-weekly teriparatide. Are bone turnover markers
      useful in predicting fracture risk?

PMID- 24579908
TI  - Naphthenic acids in coastal sediments after the Hebei Spirit oil spill: a
      potential indicator for oil contamination.
AB  - Naphthenic acids (NAs) as toxic components in most petroleum sources are
      suspected to be one of the major pollutants in the aquatic environment following
      oil spills, and the polarity and persistence of NAs make it a potential indicator
      for oil contamination. However, the contamination and potential effects of
      pollutants in oil spill affected areas remain unknown. To investigate NAs in oil
      spill affected areas, a sensitive method was first established for analysis of
      NAs, together with oxy-NAs in sediment samples by UPLC-QTOF-MS. Then the method
      was applied to determine the NA mixtures in crude oil, weathered oil, and
      sediments from the spilled sites after the Hebei Spirit oil spill, Taean, South
      Korea (Dec. 2007). Concentrations of NAs, O3-NAs, and O4-NAs were found to be 7.8
      130, 3.6-44, and 0.8-20 mg kg(-1) dw in sediments from the Taean area,
      respectively, which were much greater than those measured in the reference sites
      of Manlipo and Anmyundo beaches. Concentrations of NAs were 50-100 times greater
      than those (0.077-2.5 mg kg(-1) dw) of PAHs in the same sediment samples, thus
      the ecological risk of NAs in oil spill affected areas deserves more attention.
      The sedimentary profiles of oil-derived NAs and background NAs centered around
      compounds with 21-35 and 12-21 carbons, respectively, indicating that the crude
      derived NA mixtures originating from the 2007 oil spill were persistent. Acyclic
      NAsn=5-20 were easily degraded compared to cyclic NAsn=21-41 during the oil
      weathering processes, and the ratio of oxy-NAsn=21-41 relative to NAsn=21-41
      could be a novel index to estimate the degree of oil weathering in sediments.
      Altogether, the persistent oil-derived NAsn=21-41 could be used as a potential
      indicator for oil-specific contamination, as such compounds would not be much
      affected by the properties of coastal sediments possibly due to the high sorption
      of the negatively charged compounds (NAs) in sediment. 

PMID- 24579909
TI  - Goal internalization and persistence as a function of autonomous and directive
      forms of goal support.
AB  - Two prospective studies examined the relations of autonomy support and directive
      support to goal internalization and goal persistence over a year. Study 1
      examined the role of support and internalization in semester-long goals set by
      college students and whether the goals were reset in the following semester.
      Study 2 examined semester-long goals and long-term developmental goals. Study 1
      showed that autonomy support was not only significantly associated with greater
      internalization and goal success in the fall semester, but it was also
      significantly associated with actually resetting and subsequently succeeding at
      goals that one had failed to reach. Study 2 showed that autonomy support was
      significantly associated with progress for short-term goals over the semester,
      whereas directive support was unrelated to progress. For long-term goals,
      autonomy support was significantly related to greater internalization of goals
      and to greater goal satisfaction, whereas directive support was significantly
      negatively related to these outcomes. These studies point to the beneficial
      effects of autonomy support on goal internalization and resilient persistence.
      The effects of directive support (null vs. negative) were moderated by the
      timeline of the goals. 

PMID- 24579911
TI  - Integrase strand transfer inhibitors in the management of HIV-positive
      individuals.
AB  - The use of highly active antiretroviral therapy against human immunodeficiency
      virus (HIV) can lead to rare instances of treatment failure and the emergence of
      drug resistance. HIV drug-resistant strains are archived in cellular reservoirs,
      and this can exclude the future efficacy of drugs or drug classes against which
      resistance has emerged. In addition, drug-resistant viruses can be transmitted
      between individuals. HIV drug resistance has been countered through the constant
      development of new antiretroviral drugs. Integrase strand transfer inhibitors,
      that actively block the integration of the HIV genome into the host DNA,
      represent the most recent antiretroviral drugs. Of these, raltegravir,
      elvitegravir, and dolutegravir are the only integrase strand transfer inhibitors
      that have been approved for human therapy by the US Food and Drug Administration.
      Dolutegravir is unique in its ability to seemingly evade HIV drug resistance in
      treatment-naive individuals. Here, we review the use of integrase strand transfer
      inhibitors in the management of HIV, focusing on HIV resistance.

PMID- 24579910
TI  - 5,6-Dihydropyrimidine peroxyl radical reactivity in DNA.
AB  - Nucleobase radicals are a major family of reactive species produced in DNA as a
      result of oxidative stress. Two such radicals, 5-hydroxy-5,6-dihydrothymidin-6-yl
      radical (1) and 5,6-dihydrouridin-6-yl radical (5), were independently generated
      within chemically synthesized oligonucleotides from photochemical precursors.
      Neither nucleobase radical produces direct strand breaks or alkali-labile lesions
      in single or double stranded DNA. The respective peroxyl radicals, resulting from
      O2 trapping, add to 5'-adjacent nucleobases, with a preference for dG. Distal
      dG's are also oxidatively damaged by the peroxyl radicals. Experiments using a
      variety of sequences indicate that distal damage occurs via covalent modification
      of the 5'-adjacent dG, but there is no evidence for electron transfer by the
      nucleobase peroxyl radicals. 

PMID- 24579912
TI  - Pharmacotherapy for hospital-acquired pneumonia.
AB  - INTRODUCTION: Hospital-acquired pneumonia is the most common life-threatening
      hospital-acquired infection, and the majority of cases are associated with
      mechanical ventilation. Once pneumonia develops, the appropriateness of the
      initial antibiotic regimen is a vital determinant of outcome. The slow rate of
      development of newer antimicrobials has led to the rediscovery of the 'old' and
      'forgotten' antibiotic 'Colistin', and it is increasingly being used as salvage
      therapy in patients with multidrug-resistant gram-negative bacteria infections.
      AREAS COVERED: This article covers medical literature published in any language
      since 1990 until November 2011, on 'hospital pneumonia', identified using PubMed,
      MEDLINE and clinicaltrial.gov. The search terms used were 'ventilator associated
      pneumonia', 'management' and 'new antibiotics'. EXPERT OPINION: Many
      controversies still remain in the management of hospital-acquired pneumonia. A
      continuous evaluation of the antimicrobial therapeutic options, along with their
      pharmacodynamic and pharmacokinetic profiles, is mandatory to optimize therapy
      and reduce hospital pneumonia-related mortality.

PMID- 24579914
TI  - Glutamyl-tRNAGln amidotransferase is essential for mammalian mitochondrial
      translation in vivo.
AB  - Translational accuracy depends on the correct formation of aminoacyl-tRNAs,
      which, in the majority of cases, are produced by specific aminoacyl-tRNA
      synthetases that ligate each amino acid to its cognate isoaceptor tRNA.
      Aminoacylation of tRNAGln, however, is performed by various mechanisms in
      different systems. Since no mitochondrial glutaminyl-tRNA synthetase has been
      identified to date in mammalian mitochondria, Gln-tRNAGln has to be formed by an
      indirect mechanism in the organelle. It has been demonstrated that human
      mitochondria contain a non-discriminating glutamyl-tRNA synthetase and the
      heterotrimeric enzyme GatCAB (where Gat is glutamyl-tRNAGln amidotransferase),
      which are able to catalyse the formation of Gln-tRNAGln in vitro. In the present
      paper we demonstrate that mgatA (mouse GatA) interference in mouse cells produces
      a strong defect in mitochondrial translation without affecting the stability of
      the newly synthesized proteins. As a result, interfered cells present an
      impairment of the oxidative phosphorylation system and a significant increase in
      ROS (reactive oxygen species) levels. MS analysis of mitochondrial proteins
      revealed no glutamic acid found in the position of glutamines, strongly
      suggesting that misaminoacylated Glu-tRNAGln is rejected from the translational
      apparatus to maintain the fidelity of mitochondrial protein synthesis in mammals.

PMID- 24579913
TI  - The SmartCAT: an m-health platform for ecological momentary intervention in child
      anxiety treatment.
AB  - INTRODUCTION: Cognitive behavioral therapy (CBT) for child anxiety, although
      efficacious, typically requires 16-20 weekly sessions with a therapist. Brief CBT
      (BCBT; eight sessions) for child anxiety is promising but may have less favorable
      outcomes owing to reduced session time. Mobile health (m-health) has the
      potential to improve BCBT efficacy by delivering ecological momentary
      intervention to engage youth in learning and practicing CBT skills in their
      everyday lives (in vivo). MATERIALS AND METHODS: We developed an m-health
      platform entitled SmartCAT (Smartphone-enhanced Child Anxiety Treatment).
      SmartCAT consists of (1) a smartphone application (app) that cues youth to use
      the CBT skills taught in sessions, (2) an online portal that allows therapists to
      monitor skill use, to send cues and treatment-related materials, to engage youth
      in real-time via secure messages, and to manage rewards, and (3) a communication
      protocol that allows real-time bidirectional exchange between the app and the
      portal. A pilot study with nine youth (9-14 years old) examined the platform's
      feasibility as an adjunct to BCBT. RESULTS: SmartCAT was found to be capable of
      supporting BCBT for child anxiety and received positive feedback from both
      therapists and youth patients. Patients rated the app as highly usable (mean=1.7
      on a 1-7 scale, with 1="easy"). Patients completed 5.36 skills coach entries per
      session (standard deviation=1.95) and took an average of 3.14 min (standard
      deviation=0.98 min) to complete the entries. CONCLUSIONS: A smartphone app is
      feasible within CBT for child anxiety. Users found SmartCAT both acceptable and
      easy to use. Integrating an m-health platform within BCBT for anxious children
      may facilitate involvement in treatment and dissemination of effective
      procedures.

PMID- 24579915
TI  - Stroke hospitalizations over three decades: lower for men, unchanged for women. A
      population-based study.
AB  - BACKGROUND: Several reports suggest that stroke incidence is gradually declining,
      possibly owing to improvements in primary and secondary prevention. The objective
      of our study was to assess whether the trends of stroke hospitalization rates,
      common risk factors, and in-hospital outcomes affected both males and females
      similarly. METHODS: A retrospective review was made of discharge letters of acute
      ischemic stroke hospitalizations during 1988, 1996, and 2006 in a tertiary
      referral hospital. Data regarding demographics, common risk factors, and the in
      hospital outcomes were collected. RESULTS: A total of 1,287 cases were recorded
      (mean age 68.7 +/- 11.8 years, 53.3% males). The annual age-adjusted rates of
      stroke hospitalizations per 1,000 persons in 1988, 1996, and 2006 were 2.31,
      1.64, and 1.64, respectively (p<0.001). The age-adjusted rates decreased in males
      (3.0, 1.77, and 1.67; p<0.001); there was no significant trend among females
      (1.68, 1.53, and 1.62; p = 0.864). The positive trends of age-adjusted rates of
      hypertension and dyslipidemia were significantly steeper in females than in
      males. No significant difference in the trends of adjusted in-hospital mortality
      rates between the sexes was found. Significant decline in the length of stay was
      demonstrated for both sexes, with no significant difference in the measure of
      decline between the groups. CONCLUSIONS: Stroke hospitalization rates decreased
      for men but not for women. Regardless of whether the discordance in stroke
      incidence trends between males and females was caused by biological factors
      (different risk factor profile) or disparities in healthcare provision, it seems
      that the challenge of stroke prevention in the next decade is in lowering the
      risk of stroke in females.

PMID- 24579916
TI  - Ethnicity moderates the association between 5-HTTLPR and national suicide rates.
AB  - The association between ethnicity, national suicide rates, and the functional
      serotonin transporter gene polymorphism (5-HTTLPR), under consideration of the
      role of economic indicators, national alcohol intake, and national happiness
      scores was analyzed with an ecologic analysis. Data on allelic frequencies of the
      short (s) allele from 38 countries from over 100,000 healthy screened or general
      population individuals were analyzed with multiple regression models. Allele
      frequency varied widely both within and across ethnicities and an ethnicity-based
      interaction between national suicide rates and 5-HTTLPR allele frequency was
      revealed with the s allele acting as protective factor in Caucasian and as a risk
      factor in non-Caucasian populations. This interaction effect underlines the
      importance of ethnicity as a moderating factor in the genetics of suicide. 

PMID- 24579917
TI  - Suicide and unemployment: a panel analysis of Canadian provinces.
AB  - The objective of this study was to investigate the causal relationship between
      suicide and unemployment. We use panel data from Canadian provinces and use
      recent panel econometric techniques to account for endogenous structural breaks
      in both the unit root and cointegration testing procedures in order to account
      for statistical specification issues. We find that the relationship between
      unemployment and suicide is context dependent. We do find positive and
      statistically significant relationships, but only for males in particular
      provinces. The relationship between unemployment and suicide is not monolithic.
      Rather, relationships are not always as expected for different demographic groups
      and all places. 

PMID- 24579918
TI  - Comparisons of prisoners who make or do not make suicide attempts and further who
      make one or multiple attempts.
AB  - Suicidal behavior among prisoners is a major problem. The objective of this study
      was to compare prisoners who have made an attempt at suicide vs non-attempters
      and further to compare single vs multiple suicide attempts. Among 1,537
      prisoners, 200 (13%) had a lifetime history of attempting suicide and 92 (6%) had
      made multiple attempts. Those who had made multiple or single attempts were
      compared on socio-demographic, developmental, personality, forensic, and
      psychiatric variables. In a re-analysis we also compared non-attempters with
      attempters in this larger sample. The comparison showed that prisoners who had
      made multiple attempts had experienced significantly more childhood trauma, were
      more introverted, less resilient, had a history of self-mutilation, and had more
      suicidal ideation. Anger and hostility scores and criminal and violence histories
      significantly differentiated prisoners who had attempted from those who had never
      attempted but they did not differentiate multiple from single attempters. Having
      a history of multiple attempts may be indicative of more severe psychopathology
      in prisoners, as found in other populations. These findings may be helpful in
      predicting which prisoner is at increased risk of exhibiting suicidal behavior
      while incarcerated and after release. 

PMID- 24579919
TI  - Aggressiveness across development and suicidal behavior in depressed patients.
AB  - The objective of this study was to determine differences in the pathway of
      aggressiveness across development between depressive subjects and normal
      controls, and to examine males and females separately with regard to level of
      aggression and suicidal behavior among depressed subjects. Participants were
      classified into 5 groups: depressed suicide attempters (DSA; n = 339), depressed
      non-suicide attempters (DNSA; n = 92), psychiatric controls who had attempted
      suicide (PSA; n = 188), psychiatric controls who had not attempted suicide (PNSA;
      n = 222), and normal controls (NC; n = 532). The level of aggressiveness across
      development in the different groups was examined using a 5 (DSA vs. DNSA vs. PSA
      vs. PNSA vs. NC)*3 (Childhood, Adolescence, and Adulthood) MANCOVA. Adjusted and
      separate models for males and females were conducted. Depressed subjects differed
      in severity of aggressiveness. The level of aggressiveness in individuals in the
      NC group remained stable across development, while subjects in the DSA and DNSA
      groups showed significantly higher levels of aggressiveness. This finding was
      also observed in subjects of the PSA and PNSA groups. The level of aggressiveness
      in males with depression significantly increased over time. In women, increasing
      levels of aggressiveness across development were only observed in depressed
      suicide attempters. Limitations of this study included use of semi-structured
      interview for the assessment of risk factors. We found significant differences in
      severity and in the pathway of aggressiveness across development between
      depressive subjects and normal controls. In addition, sex differences regarding
      level of aggression and suicidal behavior among depressed subjects were found. 

PMID- 24579920
TI  - Methylerythritol and mevalonate pathway contributions to biosynthesis of mono-,
      sesqui-, and diterpenes in glandular trichomes and leaves of Stevia rebaudiana
      Bertoni.
AB  - The biosynthesis of the diterpenoid steviol glycosides rebaudioside A and
      stevioside in nonrooted cuttings of Stevia rebaudiana was investigated by feeding
      experiments using the labeled key precursors [5,5-(2)H2]-mevalonic acid lactone
      (d2-MVL) and [5,5-(2)H2]-1-deoxy-d-xylulose (d2-DOX). Labeled glycosides were
      extracted from the leaves and stems and were directly analyzed by LC-(-ESI)-MS/MS
      and by GC-MS after hydrolysis and derivatization of the resulting isosteviol to
      the corresponding TMS-ester. Additionally, the incorporation of the proffered d2
      MVL and d2-DOX into volatile monoterpenes, sesquiterpenes, and diterpenes in
      glandular trichomes on leaves and stems was investigated by headspace-solid phase
      microextraction-GC-MS (HS-SPME-GC-MS). Incorporation of the labeled precursors
      indicated that diterpenes in leaves and monoterpenes and diterpenes in glandular
      trichomes are predominately biosynthesized via the methylerythritol phosphate
      (MEP) pathway, whereas both the MEP and mevalonate (MVA) pathways contribute to
      the biosynthesis of sesquiterpenes at equal rates in glandular trichomes. These
      findings give evidence for a transport of MEP pathway derived farnesyl
      diphosphate precursors from plastids to the cytosol. Contrarily, the transport of
      MVA pathway derived geranyl diphosphate and geranylgeranyl diphosphate precursors
      from the cytosol to the plastid is limited.

PMID- 24579921
TI  - Deficits in egocentric-updating and spatial context memory in a case of
      developmental amnesia.
AB  - Patients with developmental amnesia usually suffer from both episodic and spatial
      memory deficits. DM, a developmental amnesic, was impaired in her ability to
      process self-motion (i.e., idiothetic) information while her ability to process
      external stable landmarks (i.e., allothetic) was preserved when no self-motion
      processing was required. On a naturalistic and incidental episodic task, DM was
      severely and predictably impaired on both free and cued recall tasks.
      Interestingly, when cued, she was more impaired at recalling spatial context than
      factual or temporal information. Theoretical implications of that co-occurrence
      of deficits and those dissociations are discussed and testable cerebral
      hypothesis are proposed. 

PMID- 24579922
TI  - Garcinielliptone FC, a polyisoprenylated benzophenone from Platonia insignis
      Mart., promotes vasorelaxant effect on rat mesenteric artery.
AB  - Polyisoprenylated benzophenones represent a group of chemical compounds commonly
      identified in Clusiaceae species and are responsible for a large amount of
      biological activities. In this work, the vasorelaxant effect induced by
      garcinielliptone FC (GFC) isolated from Platonia insignis Mart. (Clusiaceae), a
      monotype species from Platonia genus, was investigated. GFC promoted an
      endothelium-independent vasorelaxation on phenylephrine (PHE, 10(-5) mol L(-1))
      induced vasoconstriction, but not on KCl (80 mmol L(-1))-induced
      vasoconstriction, on rat superior mesenteric artery rings. In addition, a
      concentration-dependent decrease of PHE- or serotonin-induced cumulative
      concentration-response curves was observed for GFC, and a slight decrease of pD2
      value on CaCl2-induced vasoconstriction. In a Ca(2+)-free medium, GFC interfered
      in calcium mobilisation from PHE (10(-5) mol L(-1))-sensitive intracellular
      stores. GFC-induced vasorelaxant effect is probably mediated by a dual effect on
      mobilisation of calcium intracellular stores and attenuation of transmembrane
      calcium influx.

PMID- 24579923
TI  - A randomised controlled trial of intra-uterine insemination versus in vitro
      fertilisation in patients with idiopathic or mild male infertility.
AB  - BACKGROUND: The cause of infertility is unexplained or poorly explained in 30-40%
      of couples undergoing standard investigations, and treatment ranges from
      expectant management to IUI and IVF. AIMS: The aim of this study was to compare
      the clinical pregnancy rates and costs of intra-uterine insemination (IUI) and in
      vitro fertilisation (IVF) in women where the same ovarian stimulation led to the
      development of two or three mature follicles. METHODS: A randomised controlled
      clinical trial compared the efficacy of IUI and IVF in a tertiary fertility
      centre (ISRCTN28780587). Primary outcome measures were fetal heart positive
      pregnancy rate and cost per live birth. The selection criteria were age: females
      18-42 years and males 18-60 years, infertility for one year or more, no IVF or
      IUI for 12 months prior to the trial, and no coital, tubal or ovulatory
      disorders, oligospermia, untreated endometriosis or contraindication for multiple
      pregnancy. All women (n = 102) had the same dose FSH stimulation protocol. Those
      who developed two or three preovulatory follicles were randomised 3:1 to IUI (n =
      33) or IVF (n = 10). IUI or IVF was performed 36 h after hCG administration with
      single or double embryo transfer on day two. RESULTS: Clinical pregnancy rates
      (40% vs 12%, P = 0.04) and live birth rate (40% vs 6%, P = 0.01) were higher for
      IVF than IUI. The cost per live birth was AU$8735 for IVF compared with $42,487
      for IUI. CONCLUSIONS: This study provides evidence that IVF is more successful
      and cost-effective than IUI using the same doses of FSH. Further confirmatory
      studies are required.

PMID- 24579924
TI  - The mediation effect of menstrual phase on negative emotion processing: evidence
      from N2.
AB  - Numerous studies have shown a 'negativity bias' in emotion processing and effect
      of menstrual phase on emotion processing. Most of these results, however, did not
      match the arousal of different types of stimuli. The present study examined the
      time course of negative emotion processing across different menstrual phases
      (e.g., late luteal/premenstrual phase and follicular phase) when the arousal
      level of negative and neutral stimuli was equal. Following previous studies, an
      oddball paradigm was utilized in present study. Participants viewed neutral and
      negative (highly (HN) and moderately negative (MN)) stimuli with matched arousal
      and were asked to make deviant vs. standard judgments. The behavioral results
      showed a higher accuracy for HN stimuli than neutral stimuli, and the other
      comparisons were not significant. The major event-related potential (ERP) finding
      was that N2 amplitude was larger for MN than neutral in the late luteal phase,
      whereas such difference was absent during the follicular phase. Moreover, The N2
      for HN stimuli was larger in late luteal phase than in follicular phase.
      Therefore, female may be with higher sensitivity to MN stimuli during late luteal
      phase than during follicular phase when the arousal of stimuli was well
      controlled. These results provide additional insight to premenstrual affective
      syndrome and affective disorder. 

PMID- 24579925
TI  - Histopathologic features of transplant glomerulopathy associated with response to
      therapy with intravenous immune globulin and rituximab.
AB  - Transplant glomerulopathy (TG) is associated with poor long-term allograft
      survival and is often accompanied by microcirculation inflammation.
      Histopathologic scoring may inform prognosis and help guide therapy. We
      retrospectively assessed 33 patients with biopsy-proven TG. All biopsies were
      given a glomerulitis (g) and peritubular capillaritis (ptc) score. We determined
      allograft survival and serum creatinine stability in three different score
      groups: g < 2 and >= 2, ptc < 2 and >= 2, and (g + ptc) < 4 and >= 4. We assessed
      the impact of treatment with intravenous immune globulin (IVIG) and rituximab on
      outcomes. Graft survival and serum creatinine stability did not differ in each of
      the histopathologic score groups. Higher-score groups were associated with the
      presence of concomitant antibody-mediated rejection and were more likely to
      receive IVIG and rituximab. Treatment with IVIG and rituximab resulted in
      stability of serum creatinine within the higher-score groups, but not in the
      lower-score groups. Stabilization of serum creatinine was associated with an
      improvement in donor-specific antibody. Histopathologic scoring in kidney
      allograft biopsies with TG may help guide treatment. The combination of IVIG and
      rituximab appears to be beneficial in patients whose biopsies have moderate or
      severe microvascular injury.

PMID- 24579926
TI  - Everolimus for patients with mantle cell lymphoma refractory to or intolerant of
      bortezomib: multicentre, single-arm, phase 2 study.
AB  - The multicentre, open-label, two-stage, single-arm, phase 2, PILLAR (PIvotaL
      Lymphoma triAls of RAD001)-1 study (NCT00702052) assessed the efficacy and safety
      of everolimus 10 mg/d in adults with confirmed mantle cell lymphoma (MCL)
      refractory to or intolerant of bortezomib who received >=1 other antineoplastic
      agent, either separately or in combination with bortezomib. Primary endpoint was
      overall response rate (ORR) per investigator review according to the response
      criteria for malignant lymphoma. Secondary endpoints included progression-free
      survival (PFS), overall survival (OS) and safety. Fifty-eight patients were
      enrolled from August 2008-January 2011. Five partial responses were observed (ORR
      8.6%; 90% confidence interval [CI] 3.5-17.3%); the study did not meet the
      prespecified objective of >=8 objective responses among 57 patients. Median PFS
      and OS were 4.4 months (95% CI 3.5-6.1) and 16.9 months (95% CI 14.4-29.9),
      respectively. Grade 3/4 non-haematological toxicities occurred in 70.7% of
      patients. Based on laboratory values, grade 3/4 thrombocytopenia, neutropenia and
      anaemia occurred in 13.8%, 13.8% and 8.6% of patients, respectively. Everolimus
      demonstrated modest activity and acceptable tolerability in heavily pretreated
      patients with MCL refractory to or intolerant of bortezomib. Future studies
      evaluating everolimus in a less refractory population or in combination with
      other targeted therapies in refractory MCL are warranted. 

PMID- 24579928
TI  - Methane production and methanogenic archaeal communities in two types of paddy
      soil amended with different amounts of rice straw.
AB  - Soil type and returning straw to the field are the important factors that
      regulate CH4 formation in paddy soil, and the variations of biogeochemical
      parameters and methanogens communities play important roles in the formation of
      CH4 . In the present study, two paddy soil types [silt loam soil (JX) and silty
      clay loam soil (GD)] with different amounts of rice straw additions were
      incubated under anaerobic conditions to investigate the relationship between CH4
      production, biogeochemical variations, and methanogenic archaeal communities.
      Straw incorporation significantly stimulated CH4 production in two soil types.
      CH4 production in JX soil was higher than the GD soil with equal straw addition.
      Significant differences between biogeochemical parameters and methanogenic
      archaeal communities were observed between two soil types. Straw addition
      increased archaeal 16S rRNA genes and mcrA genes copy numbers, especially in JX
      soil. Multiple regression analysis indicated that variations in H2 , sulfate, Fe
      (II) concentrations, archaeal 16S rRNA genes and mcrA genes copy numbers,
      methanogens diversity index, and the relative abundance of Methanosarcinaceae and
      Methanobacteriaceae together influenced CH4 production in two soil types. These
      results indicated that methane production was influenced by the comprehensive
      effects of biotic and abiotic factors in paddy soils.

PMID- 24579929
TI  - Sulfated-polysaccharide fraction extracted from red algae Gracilaria birdiae
      ameliorates trinitrobenzenesulfonic acid-induced colitis in rats.
AB  - OBJECTIVES: The aim of this study was to evaluate the protective effect of the
      sulfated-polysaccharide (PLS) fraction extracted from the seaweed Gracilaria
      birdiae in rats with trinitrobenzenesulfonic acid (TNBS)-induced colitis.
      METHODS: In the experiments involving TNBS-induced colitis, rats were pretreated
      with polysaccharide extracted from G. birdiae (PLS: 30, 60 and 90 mg/kg, 500 MUL
      p.o.) or dexamethasone (control group: 1 mg/kg) once daily for 3 days starting
      before TNBS instillation (day 1). The rats were killed on the third day, the
      portion of distal colon was excised and washed with 0.9% saline and pinned onto a
      wax block for the evaluation of macroscopic scores. Samples of the intestinal
      tissue were used for histological evaluation and assays for glutathione (GSH)
      levels, malonyldialdehyde (MDA) concentration, myeloperoxidase (MPO) activity,
      nitrate and nitrite (NO3 /NO2 ) concentration and cytokines levels. KEY FINDINGS:
      PLS treatment reduced the macroscopic and microscopic TNBS-induced intestinal
      damage. Additionally, it avoided the consumption of GSH, decreased pro
      inflammatory cytokine levels, MDA and NO3 /NO2 concentrations and diminished the
      MPO activity. CONCLUSIONS: Our results suggest that the PLS fraction has a
      protective effect against intestinal damage through mechanisms that involve the
      inhibition of inflammatory cell infiltration, cytokine releasing and lipid
      peroxidation.

PMID- 24579930
TI  - High density ozone monitoring using gas sensitive semi-conductor sensors in the
      Lower Fraser Valley, British Columbia.
AB  - A cost-efficient technology for accurate surface ozone monitoring using gas
      sensitive semiconducting oxide (GSS) technology, solar power, and automated cell
      phone communications was deployed and validated in a 50 sensor test-bed in the
      Lower Fraser Valley of British Columbia, over 3 months from May-September 2012.
      Before field deployment, the entire set of instruments was colocated with
      reference instruments for at least 48 h, comparing hourly averaged data. The
      standard error of estimate over a typical range 0-50 ppb for the set was 3 +/- 2
      ppb. Long-term accuracy was assessed over several months by colocation of a
      subset of ten instruments each at a different reference site. The differences
      (GSS-reference) of hourly average ozone concentration were normally distributed
      with mean -1 ppb and standard deviation 6 ppb (6000 measurement pairs).
      Instrument failures in the field were detected using network correlations and
      consistency checks on the raw sensor resistance data. Comparisons with modeled
      spatial O3 fields demonstrate the enhanced monitoring capability of a network
      that was a hybrid of low-cost and reference instruments, in which GSS sensors are
      used both to increase station density within a network as well as to extend
      monitoring into remote areas. This ambitious deployment exposed a number of
      challenges and lessons, including the logistical effort required to deploy and
      maintain sites over a summer period, and deficiencies in cell phone
      communications and battery life. Instrument failures at remote sites suggested
      that redundancy should be built into the network (especially at critical sites)
      as well as the possible addition of a "sleep-mode" for GSS monitors. At the
      network design phase, a more objective approach to optimize interstation
      distances, and the "information" content of the network is recommended. This
      study has demonstrated the utility and affordability of the GSS technology for a
      variety of applications, and the effectiveness of this technology as a means
      substantially and economically to extend the coverage of an air quality
      monitoring network. Low-cost, neighborhood-scale networks that produce reliable
      data can be envisaged. 

PMID- 24579931
TI  - Hematopoietic stem cell gene therapy: progress on the clinical front.

PMID- 24579927
TI  - Phosphatase of regenerating liver: a novel target for cancer therapy.
AB  - INTRODUCTION: Phosphatases of regenerating livers (PRLs) are novel oncogenes that
      interact with many well-established cell signaling pathways that are misregulated
      in cancer, and are known to drive cancer metastasis when overexpressed. AREAS
      COVERED: This review covers basic information of the discovery and
      characteristics of the PRL family. We also report findings on the role of PRL in
      cancer, cell functions and cell signaling. Furthermore, PRL's suitability as a
      novel drug target is discussed along with current methods being developed to
      facilitate PRL inhibition. EXPERT OPINION: PRLs show great potential as novel
      drug targets for anticancer therapeutics. Studies indicate that PRL can perturb
      major cancer pathways such as Src/ERK1/2 and PTEN/PI3K/Akt. Upregulation of PRLs
      has also been shown to drive cancer metastasis. However, in order to fully
      realize its therapeutic potential, a deeper understanding of the function of PRL
      in normal tissue and in cancer must be obtained. Novel and integrated
      biochemical, chemical, biological, and genetic approaches will be needed to
      identify PRL substrate(s) and to provide proof-of-concept data on the
      druggability of the PRL phosphatases.

PMID- 24579932
TI  - Guided growth of horizontal GaN nanowires on quartz and their transfer to other
      substrates.
AB  - The guided growth of horizontal nanowires has so far been demonstrated on a
      limited number of substrates. In most cases, the nanowires are covalently bonded
      to the substrate where they grow and cannot be transferred to other substrates.
      Here we demonstrate the guided growth of well-aligned horizontal GaN nanowires on
      quartz and their subsequent transfer to silicon wafers by selective etching of
      the quartz while maintaining their alignment. The guided growth was observed on
      different planes of quartz with varying degrees of alignment. We characterized
      the crystallographic orientations of the nanowires and proposed a new mechanism
      of "dynamic graphoepitaxy" for their guided growth on quartz. The transfer of the
      guided nanowires enabled the fabrication of back-gated field-effect transistors
      from aligned nanowire arrays on oxidized silicon wafers and the production of
      crossbar arrays. The guided growth of transferrable nanowires opens up the
      possibility of massively parallel integration of nanowires into functional
      systems on virtually any desired substrate. 

PMID- 24579933
TI  - Distinguishing patients with stage I lung cancer versus control individuals using
      serum mass profiling.
AB  - Serum mass profiling can discern physiological changes associated with specific
      disease states and their progression. Sera (86 total) from control individuals
      and patients with stage I nonsmall cell lung cancer or benign small pulmonary
      nodules were discriminated retrospectively by serum changes discerned by mass
      profiling. Control individuals were distinguished from patients with Stage I lung
      cancer or benign nodules with test sensitivities of 89% and 83%. Lung cancer
      patients versus those with benign nodules were distinguished with 80%
      sensitivity. This study exhibits progress toward a minimally-invasive aid in
      early detection of lung cancer and monitoring small pulmonary nodules for
      malignancy. 

PMID- 24579934
TI  - Correlating catalytic activity of Ag-Au nanoparticles with 3D compositional
      variations.
AB  - Significant elemental segregation is shown to exist within individual hollow
      silver-gold (Ag-Au) bimetallic nanoparticles obtained from the galvanic reaction
      between Ag particles and AuCl4(-). Three-dimensional compositional mapping using
      energy dispersive X-ray (EDX) tomography within the scanning transmission
      electron microscope (STEM) reveals that nanoparticle surface segregation inverts
      from Au-rich to Ag-rich as Au content increases. Maximum Au surface coverage was
      observed for nanoparticles with approximately 25 atom % Au, which correlates to
      the optimal catalytic performance in a three-component coupling reaction among
      cyclohexane carboxyaldehyde, piperidine, and phenylacetylene. 

PMID- 24579936
TI  - Hypertension predisposes to the formation of saccular intracranial aneurysms in
      467 unruptured and 1053 ruptured patients in Eastern Finland.
AB  - OBJECTIVE: Hypertension associates with subarachnoid hemorrhage from saccular
      intracranial aneurysm (sIA-SAH) when compared to matched controls or general
      population. Few series compare hypertension in unruptured sIA versus sIA-SAH, so
      its impact on the sIA disease remains uncertain. METHODS: Kuopio sIA Database (
      www.uef.fi/ns ) contains all cases of unruptured and ruptured sIAs admitted to
      Kuopio University Hospital from its Eastern Finnish catchment population. We
      compared the age-adjusted incidence of drug-treated hypertension in 467
      unruptured and 1053 ruptured sIA patients admitted to Kuopio University Hospital
      from 1995 to 2007, using the national registry of prescribed medicines. RESULTS:
      Antihypertensive medication was more frequent in the unruptured (73% versus 62%)
      with higher age-adjusted incidence. At sIA diagnosis, the sIA-SAH group had more
      often untreated hypertension (29% versus 23%). The size of unruptured sIAs
      increased with age at sIA diagnosis, independently of hypertension. Multiple
      sIAs, familial sIA, and sIA-SAH were not associated with hypertension in
      multivariate analysis. Results indicate that drug-treated hypertension associates
      with the formation of sIAs rather than their growth or rupture. CONCLUSION:
      Hypertension is highly prevalent in the carriers of unruptured sIAs when compared
      to those with ruptured sIA. Hypertension may associate with the sIA formation,
      and may predispose to the rupture of sIA if untreated.

PMID- 24579935
TI  - Lactobacillus reuteri DSM 17938 effectively reduces the duration of acute
      diarrhoea in hospitalised children.
AB  - AIM: Guidelines consider certain probiotics useful in the management of acute
      gastroenteritis. This study evaluated the use of Lactobacillus (L) reuteri DSM
      17938. METHODS: A multicentre, randomised, single-blind clinical trial was
      performed in hospitalised children with acute gastroenteritis lasting 12-72 h.
      Children received conventional therapy with, or without, 1 * 10(8) CFU of L.
      reuteri DSM 17938 for 5 days. The primary endpoint was the duration of diarrhoea
      and secondary outcomes were days of hospitalisation and the percentage of
      children with diarrhoea after each day of treatment. RESULTS: We compared 64
      children receiving L. reuteri with 63 controls. Lactobacillus reuteri reduced the
      duration of diarrhoea after 24 h (p < 0.001) and more diarrhoea-free children
      were seen in the L. reuteri than control group after 24 and 48 h (50% versus 5%,
      p < 0.001) and 72 h (69% versus 11%, p < 0.001). Lactobacillus reuteri reduced
      mean hospital stays (4.31 +/- 1.3 days versus 5.46 +/- 1.77 days, p < 0.001).
      Prolonged diarrhoea occurred in 17% of the controls, but none of the L. reuteri
      group. No adverse effects were reported. CONCLUSION: Lactobacillus reuteri
      effectively reduced the duration of acute diarrhoea and hospital stays in
      children hospitalised with acute gastroenteritis. Outpatient data are now
      required.

PMID- 24579938
TI  - Stress-induced endocrine response and anxiety: the effects of comfort food in
      rats.
AB  - The long-term effects of comfort food in an anxiogenic model of stress have yet
      to be analyzed. Here, we evaluated behavioral, endocrine and metabolic parameters
      in rats submitted or not to chronic unpredictable mild stress (CUMS), with access
      to commercial chow alone or to commercial chow and comfort food. Stress did not
      alter the preference for comfort food but decreased food intake. In the elevated
      plus-maze (EPM) test, stressed rats were less likely to enter/remain in the open
      arms, as well as being more likely to enter/remain in the closed arms, than were
      control rats, both conditions being more pronounced in the rats given access to
      comfort food. In the open field test, stress decreased the time spent in the
      centre, independent of diet; neither stress nor diet affected the number of
      crossing, rearing or grooming episodes. The stress-induced increase in serum
      corticosterone was attenuated in rats given access to comfort food. Serum
      concentration of triglycerides were unaffected by stress or diet, although access
      to comfort food increased total cholesterol and glucose. It is concluded that
      CUMS has an anorexigenic effect. Chronic stress and comfort food ingestion
      induced an anxiogenic profile although comfort food attenuated the endocrine
      stress response. The present data indicate that the combination of stress and
      access to comfort food, common aspects of modern life, may constitute a link
      among stress, feeding behavior and anxiety.

PMID- 24579939
TI  - Epigenetics: where environment, society and genetics meet.

PMID- 24579940
TI  - Genome-epigenome interactions: the Polycomb paradox.

PMID- 24579941
TI  - Epigenetic dysregulation in Alzheimer's disease: cause or consequence?

PMID- 24579943
TI  - Highlights from the latest articles in epigenomics.

PMID- 24579944
TI  - Human-specific CpG 'beacons' identify human-specific prefrontal cortex H3K4me3
      chromatin peaks.
AB  - BACKGROUND: Targeted recruitment of chromatin-modifying enzymes to clusters of
      CpG dinucleotides contributes toward the formation of accessible chromatin. By
      interprimate comparison we previously identified the set of nonpolymorphic human
      specific CpGs (CpG 'beacons') and revealed that these loci were enriched for
      human disease traits. Due to their human-specific CpG density change, extreme CpG
      'beacon' clusters (>=20 CpG beacons/kb) were predicted to identify permissive
      chromatin peaks within the human genome. AIM: We set out to explore these
      sequence-defined regions for evidence of an active chromatin signature. RESULTS:
      Using available comparative primate epigenomic data from neurons of the
      prefrontal cortex, we show that these CpG 'beacon' clusters are indeed enriched
      for being human-specific H3K4me3 peaks (chi(2): p < 2.2 * 10(-16)) and thus
      predictive of permissive chromatin states. These sequence regions had a higher
      predictive value than previous selective analyses. We also show that both human
      specific H3K4me3 and CpG 'beacon' clusters are increased within current and
      ancestral telomeric regions, supporting an association with recombination, which
      is higher towards the distal ends of chromosomes. CONCLUSION: Therefore, CpG
      focused comparative sequence analysis can precisely pinpoint chromatin structures
      that contribute to the human-specific phenotype and further supports an
      integrated approach in genomic and epigenomic studies.

PMID- 24579945
TI  - ADRB3 gene promoter DNA methylation in blood and visceral adipose tissue is
      associated with metabolic disturbances in men.
AB  - AIM: ADRB3 DNA hypermethylation was recently associated with dyslipidemia in
      familial hypercholesterolemia (FH). In this study, we verified whether ADRB3 DNA
      methylation in blood and visceral adipose tissue (VAT) was associated with
      obesity and its related complications. METHODS: DNA methylation levels were
      measured in the blood of 61 FH men, and the blood and VAT of 30 severely obese
      men. Common ADRB3 polymorphisms were genotyped in all subjects. RESULTS: Higher
      ADRB3 DNA methylation levels were significantly associated with lower low-density
      lipoprotein cholesterol levels (r = -0.40; p = 0.01) in FH, and with a lower
      waist-to-hip ratio (r = -0.55; p = 0.01) and higher blood pressure (r = 0.43; p =
      0.05) in severely obese men. ADRB3 g.-843C>T and p.W64R polymorphisms were found
      to be strongly associated (p < 0.001) with ADRB3 DNA methylation and mRNA levels.
      CONCLUSION: Although further studies are needed, these results suggest that
      epigenetic changes at the ADRB3 gene locus might be involved in the development
      of obesity and its related metabolic complications.

PMID- 24579946
TI  - The epigenetic landscape of aneuploidy: constitutional mosaicism leading the way?
AB  - The role of structural genetic changes in human disease has received substantial
      attention in recent decades, but surprisingly little is known about numerical
      chromosomal abnormalities, even though they have been recognized since the days
      of Boveri as partaking in different cellular pathophysiological processes such as
      cancer and genomic disorders. The current knowledge of the genetic and epigenetic
      consequences of aneuploidy is reviewed herein, with a special focus on using
      mosaic genetic syndromes to study the DNA methylation footprints and expressional
      effects associated with whole-chromosomal gains. Recent progress in understanding
      the debated role of aneuploidy as a driver or passenger in malignant
      transformation, as well as how the cell responds to and regulates excess genetic
      material in experimental settings, is also discussed in detail. 

PMID- 24579947
TI  - Discovery and development of DNA methylation-based biomarkers for lung cancer.
AB  - Lung cancer remains the primary cause of cancer-related deaths worldwide.
      Improved tools for early detection and therapeutic stratification would be
      expected to increase the survival rate for this disease. Alterations in the
      molecular pathways that drive lung cancer, which include epigenetic
      modifications, may provide biomarkers to help address this major unmet clinical
      need. Epigenetic changes, which are defined as heritable changes in gene
      expression that do not alter the primary DNA sequence, are one of the hallmarks
      of cancer, and prevalent in all types of cancer. These modifications represent a
      rich source of biomarkers that have the potential to be implemented in clinical
      practice. This perspective describes recent advances in the discovery of
      epigenetic biomarkers in lung cancer, specifically those that result in the
      methylation of DNA at CpG sites. We discuss one approach for methylation-based
      biomarker assay development that describes the discovery at a genome-scale level,
      which addresses some of the practical considerations for design of assays that
      can be implemented in the clinic. We emphasize that an integrated technological
      approach will enable the development of clinically useful DNA methylation-based
      biomarker assays. While this article focuses on current literature and primary
      research findings in lung cancer, the principles we describe here apply to the
      discovery and development of epigenetic biomarkers for other types of cancer. 

PMID- 24579948
TI  - Epigenetics: the language of the cell?
AB  - Epigenetics is one of the most rapidly developing fields of biological research.
      Breakthroughs in several technologies have enabled the possibility of genome-wide
      epigenetic research, for example the mapping of human genome-wide DNA
      methylation. In addition, with the development of various high-throughput and
      high-resolution sequencing technologies, a large number of functional noncoding
      RNAs have been identified. Massive studies indicated that these functional ncRNA
      also play an important role in epigenetics. In this review, we gain inspiration
      from the recent proposal of the ceRNAs hypothesis. This hypothesis proposes that
      miRNAs act as a language of communication. Accordingly, we further deduce that
      all of epigenetics may functionally acquire such a unique language
      characteristic. In summary, various epigenetic markers may not only participate
      in regulating cellular processes, but they may also act as the intracellular
      'language' of communication and are involved in extensive information exchanges
      within cell. 

PMID- 24579950
TI  - The epigenome in pluripotency and differentiation.
AB  - The ability to culture pluripotent stem cells and direct their differentiation
      into specific cell types in vitro provides a valuable experimental system for
      modeling pluripotency, development and cellular differentiation. High-throughput
      profiling of the transcriptomes and epigenomes of pluripotent stem cells and
      their differentiated derivatives has led to identification of patterns
      characteristic of each cell type, discovery of new regulatory features in the
      epigenome and early insights into the complexity of dynamic interactions among
      regulatory elements. This work has also revealed potential limitations of the use
      of pluripotent stem cells as in vitro models of developmental events, due to
      epigenetic variability among different pluripotent stem cell lines and epigenetic
      instability during derivation and culture, particularly at imprinted and X
      inactivated loci. This review focuses on the two most well-studied epigenetic
      mechanisms, DNA methylation and histone modifications, within the context of
      pluripotency and differentiation. 

PMID- 24579953
TI  - Scientific method and its application to chaplaincy.

PMID- 24579954
TI  - A health care chaplain's pastoral response to moral distress.
AB  - This article offers health care chaplains a pastoral response to moral distress
      experienced by health care professionals. The article offers a broad definition,
      explores its impact on health care professionals, and looks at various
      interventions to ameliorate its effects. The article goes on to clarify the
      concept of moral distress by differentiating it from the experience of moral
      dilemmas, and looking closer at the aspects of initial and reactive distress.
      After defining moral distress, the article explores two clinical models that
      create a better context to understand the phenomenon. Finally, the article
      proposes a pastoral response to moral distress from the integration of the five
      functions of pastoral care: "healing," "sustaining," "guiding," "reconciling,"
      and "nurturing" based on the work of William Clebsch, Charles Jaekle, and Howard
      Clinebell. The author then applies the pastoral response to moral distress by
      illustrating the outcome of a scenario with a critical care nurse. 

PMID- 24579955
TI  - Resilience and professional chaplaincy: a paradigm shift in focus.
AB  - Research into the area of resilience provides a challenge and a great opportunity
      for professional chaplaincy. In this article, we will consider the challenge that
      the research primarily of George Bonanno of Columbia University offers to the
      traditional, clinical perspectives and assessments of professional chaplains
      serving in health care. Secondly, we will propose the practical implications for
      a wider paradigm and an expanded focus on intentionality and interventions of
      chaplains. Resilience is seen as a positive response possibility for those facing
      potentially traumatic events. It is understood to be a predominant response to
      traumatic events more often than the grief recovery model usually presumed to be
      active. Resilience has heuristic value and merits being factored in to
      professional chaplaincy as it relates to patient assessment, interventions,
      interdisciplinary care, staff and corporate support, and transcultural
      usefulness. 

PMID- 24579951
TI  - HDAC4: mechanism of regulation and biological functions.
AB  - The acetylation and deacetylation of histones plays an important role in the
      regulation of gene transcriptions. Histone acetylation is mediated by histone
      acetyltransferase; the resulting modification in the structure of chromatin leads
      to nucleosomal relaxation and altered transcriptional activation. The reverse
      reaction is mediated by histone deacetylase (HDAC), which induces deacetylation,
      chromatin condensation and transcriptional repression. HDACs are divided into
      three distinct classes: I, II, and III, on the basis of size and sequence
      homology, as well as formation of distinct complexes. Among class II HDACs, HDAC4
      is implicated in controlling gene expression important for diverse cellular
      functions. Basic and clinical experimental evidence has established that HDAC4
      performs a wide variety of functions. Understanding the biological significance
      of HDAC4 will not only provide new insight into the mechanisms of HDAC4 involved
      in mediating biological response, but also form a platform to develop a
      therapeutic strategy to achieve clinical implications. 

PMID- 24579956
TI  - Research designs and making causal inferences from health care studies.
AB  - This article summarizes the major types of research designs used in healthcare
      research, including experimental, quasi-experimental, and observational studies.
      Observational studies are divided into survey studies (descriptive and
      correlational studies), case-studies and analytic studies, the last of which are
      commonly used in epidemiology: case-control, retrospective cohort, and
      prospective cohort studies. Similarities and differences among the research
      designs are described and the relative strength of evidence they provide is
      discussed. Emphasis is placed on five criteria for drawing causal inferences that
      are derived from the writings of the philosopher John Stuart Mill, especially his
      methods or canons. The application of the criteria to experimentation is
      explained. Particular attention is given to the degree to which different designs
      meet the five criteria for making causal inferences. Examples of specific studies
      that have used various designs in chaplaincy research are provided. 

PMID- 24579958
TI  - Genetic polymorphisms in IL-2, IL-10, TGF-beta1, and IL-2RB and acute rejection
      in renal transplant patients.
AB  - Acute rejection (AR) remains a concern for kidney transplantation. Cytokines are
      key mediators in the induction and effector phases of all immune and inflammatory
      responses. Single nucleotide polymorphisms (SNPs) in cytokines and their
      receptors may relate to AR. We investigated the relation between AR and SNPs in
      the genes encoding for IL-2(-330G>T), IL-10(-592C>A and -1082G>A), TGF
      beta1(915G>C), and IL-2RB(rs228942 C>A and rs228953 C>T) in 325 renal transplant
      patients during the first year after transplantation. The overall incidence of AR
      was 15.4%. In multivariate analysis, only the use of induction therapy was
      correlated with AR (odds ratio 1.9; 95% confidence interval 1.1-3.7; p = 0.04).
      No statistically significant associations between the SNPs studied and AR were
      observed. SNPs in the investigated cytokines and their receptors were not
      associated with the risk of AR. Genotyping patients for these SNPs is unlikely to
      aid the clinician in adjusting the immunosuppressive therapy for individual
      patients.

PMID- 24579959
TI  - Anthocyanin structure determines susceptibility to microbial degradation and
      bioavailability to the buccal mucosa.
AB  - Anthocyanins are flavonoids with reported chemoprotective activities in the oral
      cavity. However, information about their stability, metabolism, and tissue uptake
      in the mouth is limited. Anthocyanin chemical structure was recently shown to
      affect their stability ex vivo in saliva, and it was hypothesized that structure
      may affect their availability in oral tissues in vivo. Here, 12 healthy
      individuals retained red grape or chokeberry juice in the mouth for 5 min.
      Anthocyanin stability, mucus binding, and uptake into epithelial cells were
      evaluated. Loss of delphinidin-3-glucoside in red grape juice exceeded that of
      other anthocyanin-glucosides, and lesser amounts of delphinidin- and petunidin
      glucosides were associated with buccal scraping, suggesting the loss was due to
      degradation. In chokeberry juice, loss of cyanidin-3-xyloside exceeded that of
      other anthocyanins, whereas cyanidin-3-glucoside preferentially accumulated in
      epithelium cells. These results suggest that anthocyanin structure affects
      stability and buccal cell uptake and therefore the potential efficacy of
      anthocyanin-rich products for the promotion of oral health. 

PMID- 24579960
TI  - Mutual influences between partners' hormones shape conflict dialog and
      relationship duration at the initiation of romantic love.
AB  - Early-stage romantic love involves reorganization of neurohormonal systems and
      behavioral patterns marked by mutual influences between the partners' physiology
      and behavior. Guided by the biobehavioral synchrony conceptual frame, we tested
      bidirectional influences between the partners' hormones and conflict behavior at
      the initiation of romantic love. Participants included 120 new lovers (60
      couples) and 40 singles. Plasma levels of five affiliation and stress-related
      hormones were assessed: oxytocin (OT), prolactin (PRL), testosterone (T),
      cortisol (CT), and dehydroepiandrosterone sulfate (DHEAS). Couples were observed
      in conflict interaction coded for empathy and hostility. CT and DHEAS showed
      direct actor effects: higher CT and DHEAS predicted greater hostility. OT showed
      direct partner effects: individuals whose partners had higher OT showed greater
      empathy. T and CT showed combined actor-partner effects. High T predicted greater
      hostility only when partner also had high T, but lower hostility when partner had
      low T. Similarly, CT predicted low empathy only in the context of high partner's
      CT. Mediational analysis indicated that combined high CT in both partners was
      associated with relationship breakup as mediated by decrease in empathy. Findings
      demonstrate the mutual influences between hormones and behavior within an
      attachment bond and underscore the dynamic, co-regulated, and systemic nature of
      pair-bond formation in humans.

PMID- 24579949
TI  - The roles of Jumonji-type oxygenases in human disease.
AB  - The iron- and 2-oxoglutarate-dependent oxygenases constitute a phylogenetically
      conserved class of enzymes that catalyze hydroxylation reactions in humans by
      acting on various types of substrates, including metabolic intermediates, amino
      acid residues in different proteins and various types of nucleic acids. The
      discovery of jumonji (Jmj), the founding member of a class of Jmj-type chromatin
      modifying enzymes and transcriptional regulators, has culminated in the discovery
      of several branches of histone lysine demethylases, with essential functions in
      regulating the epigenetic landscape of the chromatin environment. This work has
      now been considerably expanded into other aspects of epigenetic biology and
      includes the discovery of enzymatic steps required for methyl-cytosine
      demethylation as well as modification of RNA and ribosomal proteins. This
      overview aims to summarize the current knowledge on the human Jmj-type enzymes
      and their involvement in human pathological processes, including development,
      cancer, inflammation and metabolic diseases. 

PMID- 24579961
TI  - Newer targets for modulation of intraocular pressure: focus on adenosine receptor
      signaling pathways.
AB  - INTRODUCTION: The homeostatic role of adenosine in regulating intraocular
      pressure (IOP) is now widely recognized, and hence, the drugs targeting adenosine
      receptors have become the focus of investigation. In this review, we summarize
      the adenosine receptor signaling pathways, which could be potential therapeutic
      targets for the management of glaucoma. AREAS COVERED: This review presents a
      brief summary of the current hypotheses explaining the increased resistance in
      the trabecular meshwork outflow pathways and the role of adenosine in regulating
      the outflow pathway resistance. The intraocular distribution of adenosine
      receptor subtypes and their structure is described. The adenosine receptor
      signaling pathways, including activation of adenylyl cyclase, phospholipase
      inositol triphosphate-diacylglycerol and phosphatidylinositol-3-kinase and their
      link to MAPK pathways leading to changes in gene transcription are discussed in
      detail. The literature search for this review was done using PubMed using several
      key words such as adenosine, receptors, signaling pathways, trabecular meshwork,
      ciliary body, IOP, G proteins, GPCR, adenylyl cyclase, phospholipase C, ERK1/2
      and MAPKs. EXPERT OPINION: Besides adenosine receptor agonists and antagonists,
      drugs targeting intracellular signaling molecules, such as Ras proteins, small
      GTPase (Rho), Epac-specific cAMP analogs and Rap and Raf-targeted therapies may
      be useful strategies in regulating IOP.

PMID- 24579962
TI  - The osteoplastic effectiveness of the implants made of mesh titanium nickelide
      constructs.
AB  - The purpose of the work was to study the features of reparative osteogenesis for
      filling the defect of tubular bone under implantation of mesh titanium nickelide
      constructs. Tibial fenestrated defect was modeled experimentally in 30 Wistar
      pubertal rats, followed by implant intramedullary insertion. The techniques of
      radiography, scanning electron microscopy and X-ray electron probe microanalysis
      were used. The mesh implant of titanium nickelide has been established to possess
      biocompatibility, osteoconductive and osteoinductive properties, the zone of
      osteogenesis and angiogenesis is created around it, bone cover is formed.
      Osteointegration of the implant occurs early, by 7 days after surgery, and by 30
      days after surgery organotypical re-modelling of the regenerated bone takes
      place, as well as the defect is filled with lamellar bone tissue by the type of
      bone wound primary adhesion. By 30 days after surgery mineral content of the
      regenerated bone tissue approximates to the composition of intact cortex mineral
      phase. 

PMID- 24579963
TI  - Treatment of aneurysms arising from the proximal (A1) segment of the anterior
      cerebral artery.
AB  - The aim of our study was to report a series of 15 consecutive patients with
      aneurysms of the proximal segment (A1) of the anterior cerebral artery. In 15
      patients with diagnosed A1 aneurysms, representing 2.1% of 720 aneurysm patients
      treated at a University Clinical Center between October 1999 and August 2012,
      clinical presentation, neuroradiological findings, surgical treatment methods and
      outcome were retrospectively analyzed. Mean patient age was 53.06 (range 32 to
      75) years. Ten saccular aneurysms were treated with micro neurosurgical approach
      via standard pterional craniotomy, four fusiform aneurysms with coiling, and one
      fusiform aneurysm with stent. No patients died during the operation. The mean
      follow-up period was 32 months (range 5 months to 7 years). Clinical outcomes
      revealed good recovery in all patients. Despite the general opinion that A1
      aneurysms are benign lesions, an increasing number of reports have demonstrated
      their potential complications. To date, due to the rarity of A1 aneurysms, only a
      few consecutive series have been reported. Conduct of multicenter studies are
      required in order to understand clinical features of A1 aneurysms and devise a
      proper treatment plan. 

PMID- 24579964
TI  - A retrospective study on traumatic dental and soft-tissue injuries in preschool
      children in Zagreb, Croatia.
AB  - The purpose of this study was to analyze data according to gender, age, cause,
      number of traumatized teeth, time elapsed before treatment and type of tooth from
      the records of traumatized children. A retrospective study was conducted in the
      Department of Paediatric Dentistry at the University Dental Clinic in Zagreb,
      Croatia using the documentation of 128 patients (61 males and 67 females) aged 1
      month to 6 years with injuries of primary teeth between February 2009 and January
      2013. Trauma was seen in 217 primary teeth, which implies that the number of
      injured primary teeth was 1.69 per child. The maxillary central incisors were the
      most frequently affected teeth (81.1%), they were followed by maxillary lateral
      incisors, while the least affected were mandibular central incisors. Traumatic
      dental injuries involved periodontal tissue 2.82 times more frequently than hard
      dental and pulp tissue. The main cause of teeth injury was fall (67.2%) and the
      majority of injuries occurred at home (51.6%) (p<0.05). Of 128 patients who
      received treatment 71 (55.5%) also had soft-tissue injuries. The distribution of
      soft-tissue injuries by gender (35 males, 36 females) was not statistically
      significant. Comparing children with soft-tissue injuries and those without them,
      a statistically significant difference was found in the time of arrival (p<0.01).
      The results of this study showed the need of informing about preventive measures
      against falls at home and the methods of providing first aid in dental trauma
      injuries. 

PMID- 24579965
TI  - Increased coronary intervention rate among diabetic patients with poor glycaemic
      control: a cross-sectional study.
AB  - The relationship between glycaemic control and coronary artery disease (CAD) in
      type 2 diabetes mellitus (T2DM) is controversial. In the current cross-sectional
      study, we addressed the relationship between Hemoglobin A1c (HbA1c) values and
      the need for revascularization among diabetic patients undergoing coronary
      angiography. A total of 301 consecutive patients with known T2DM (age 61.8+/-10.1
      years, 46.2 % women) requiring coronary angiography due to CAD symptoms were
      included. T2DM patients were categorized into two groups based on their HbA1c
      values: 93 (30.9%) diabetics with good glycaemic control (HbA1c<=7 %), and 208
      (69.1%) diabetics with poor glycaemic control (HbA1c>7 %). A total of 123
      patients (40.9%) required revascularization. The revascularization rate was 28.0%
      among T2DM patients with good glycaemic control and 46.6% among T2DM patients
      with poor glycaemic control, respectively (p=0.002). In a logistic regression
      analysis, the need for revascularization was predicted by poor glycaemic control
      (Odds Ratio [OR] 2.26, 95% Confidence Interval [CI] 1.32-3.82; p=0.003) adjusted
      for age, gender, Body-Mass-Index and diabetes duration. Moreover, there was a
      linear relationship between HbA1c values and number of affected coronary arteries
      (r= 0.169; p=0.003). Our data suggest that there is a close association between
      poor glycaemic control and increased revascularization rate in T2DM, which should
      be considered in primary and secondary prevention models. 

PMID- 24579966
TI  - An assessment of correlation between serum asymmetric dimethylarginine and
      glycated haemoglobin in patients with type 2 diabetes mellitus.
AB  - Studies that investigated an association between asymmetric dimethylarginine
      (ADMA) and glycated haemoglobin (HbA1c) in type 2 diabetes mellitus (T2DM) have
      given discordant results. The aim of this study was to determine and compare
      serum ADMA concentration in patients with T2DM and healthy controls, and to
      assess correlation between ADMA and HbA1c in patients with T2DM. Serum ADMA
      concentration was determined by ELISA method with the use of ADMA (r) - ELISA kit
      (DLD Diagnostics, Hamburg, Germany) and HbA1c levels were determined by an
      immunoturbidimetric method in 60 patients with T2DM and 60 healthy individuals
      matched for age and sex. Results have shown that mean serum ADMA concentration
      was significantly higher in T2DM patients (1.54+/-0.06 MUmol/L) compared to mean
      serum ADMA concentration (0.62+/-0.02 MUmol/L; p<0.0001) in healthy subjects. A
      significant, positive, correlation between serum ADMA concentration and HbA1c
      levels was observed (r=0.494; p<0.01) in T2DM patients. Our results suggest that
      there is an association between endothelial dysfunction and glycaemic control in
      type 2 diabetes mellitus. Possible explanation for obtained results may be
      oxidative stress that is increased in conditions of hyperglycaemia and it also
      promotes endothelial dysfunction. Larger, longitudinal studies are required that
      will evaluate relation between metabolic abnormalities and increased ADMA levels
      in patients with type 2 diabetes mellitus. 

PMID- 24579967
TI  - Association of mannose-binding lectin 2 (mbl2) gene heterogeneity and its serum
      concentration with osteoporosis in postmenopausal women.
AB  - The aim of the study was to detect prevalence of MBL2 exon 1 (codons 52, 54 and
      57) genetic polymorphism in postmenopausal women in Bosnia and Herzegovina and
      its possible role as genetic risk factor for susceptibility to occurrence of
      osteoporosis in this study group. Also, we investigated association between MBL
      serum concentrations and osteoporosis in postmenopausal women. Genetic codons'
      variations were determined by PCR-RFLP and MBL in serum was measured by ELISA
      method in 75 postmenopausal women (37 with osteoporosis and 38 apparently
      healthy, non-osteoporotic women serving as a control). Serum MBL levels were not
      significantly different between osteoporosis and control group (492 (37-565.1)
      and 522.6 (477-559.4) ng/mL respectively, p=0.206). Genotype frequencies were not
      significantly different (p=0.997) between the studied groups of postmenopausal
      women. Genotype frequencies A/A, A/0 and 0/0 in osteoporosis group were 0.576;
      0.405; 0.018 and in control group 0.562; 0.412; 0.026, respectively. Frequencies
      of A and 0 allele were 0.78 and 0.22 in osteoporosis and 0.77 and 0.23 in control
      group. The results do not suggest association of functional polymorphism of MBL2
      gene and MBL serum concentration with osteoporosis in postmenopausal females. 

PMID- 24579968
TI  - A histological study of the effect of exogenous melatonin on gentamicin induced
      structural alterations of proximal tubules in rats.
AB  - The aim of this research was to assess the reactive changes of rat proximal
      tubules caused by gentamicin and the effect of relatively low doses of melatonin.
      48 adult male Wistar rats were distributed into six groups of equal size which
      all received one of the following daily intraperitoneal injections: vehicle (5%
      ethanol in Ringer solution) during 11 days (C); gentamicin (80 mg/kg) during 8
      days (G), two groups which concomitantly received gentamicin (80 mg/kg) during 8
      days and melatonin in two different test doses (5 or 20 mg/kg) during 11 days
      (GM1, GM2) and two groups treated only with melatonin in two different doses (5
      or 20 mg/kg) during 11 days (M1, M2). Histological analysis included qualitative
      and semi-quantitative light microscopy analysis of proximal tubules. Exogenous
      melatonin had no significant effect on the microstructure, independently of
      dosis. The changes of proximal tubules microstructure induced by gentamicin were
      expressed in the form of granulovacuolar degeneration, necrosis and desquamation.
      The grade of proximal tubular changes was smaller in animals who besides
      gentamicin received melatonin. Melatonin has a dose dependent protective effect
      on the structural alterations of proximal tubules of the kidney induced by
      gentamicin. 

PMID- 24579969
TI  - Calcitonin is expressed in the submaxillary glands of rats.
AB  - Calcitonin is usually produced by the parafollicular cells of the thyroid.
      However in an immunohistochemistry experiment we observed that the cells of the
      serous acini of rat submaxillary gland tissue were stained positive with
      calcitonin antibodies. We further used immunocytochemistry and nucleic acid
      hybridization to localize the distribution of calcitonin protein and calcitonin
      mRNA respectively in cultivated cells of rat submaxillary glands. The results
      showed that the cytoplasm of the epithelial cells of the submaxillary glands had
      positive staining in immunocytochemistry using calcitonin monoclonal antibody and
      positive reaction in nucleic acid hybridization using calcitonin mRNA
      complementary DNA probe. For the first time we found that the cells of the
      submaxillary glands of rats can produce the hormone calcitonin. 

PMID- 24579971
TI  - Unusual suspect-coronary subclavian steal syndrome caused severe myocardial
      ischemia.
AB  - Coronary-subclavian steal syndrome represents a reversal of blood flow in left
      internal mammary artery. The most common cause of the syndrome is atherosclerotic
      disease in the ipsilateral, proximal subclavian artery. We present a case of 72
      years old male, who developed severe anginal and neurological complaints three
      years after coronary artery bypass graft surgery(CABG). 

PMID- 24579970
TI  - Influence of Rho kinase inhibitor Fasudil on late endothelial progenitor cells in
      peripheral blood of COPD patients with pulmonary artery hypertension.
AB  - The objective of our work was to investigate the influence of Fasudil, a Rho
      inhibitor on the number and function of the late endothelial progenitor cells in
      peripheral blood of chronic obstructive pulmonary diseases (COPD) patients with
      pulmonary artery hypertension. Eighty 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. The control group received
      routine treatment, including oxygen uptake, anti-infection and phlegm dissolving.
      The treatment group received the Fasudil in addition to the routine treatment.
      The changes on 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. 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). The changes on the
      number and function of the late endothelial progenitor cells in peripheral blood
      and the pulmonary artery pressure before and after the treatment of the control
      group were not statistically significant (p>0.05). 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. 

PMID- 24579973
TI  - Morphology of nanostructures and their long-acting properties in vivo for a novel
      synthetic peptide of gonadotropin-releasing hormone antagonist.
AB  - OBJECTIVES: To demonstrate the correlation between the nanostructure formation
      and the long duration of action in vivo of peptides, the morphology of
      nanostructures of LXT-101, a novel synthetic amphiphilic peptide of gonadotropin
      releasing hormone antagonist were observed when dissolved in different solvents,
      and their long-acting properties in vivo were investigated in this study.
      METHODS: The morphology of nanostructures of LXT-101 was observed by transmission
      electron microscopy when dissolved in different solvents, and the plasma
      concentrations of LXT-101 and testosterone levels were also assayed for different
      solutions after intramuscular injection administration in beagle dogs. KEY
      FINDINGS: TEM data suggest that LXT-101 in pure water can form fibres, while in
      mannitol, dextrose or sodium chloride solution, they tend to form vesicles. The
      pharmacokinetic and pharmacodynamic results showed that the plasma concentrations
      of LXT-101 within 48 h were much higher but descended dramatically with mannitol,
      dextrose and NaCl solutions structurally composed of vesicles compared with that
      of pure water structurally composed of fibres. An effectively suppression of
      testosterone can be achieved only 2 or 3 days with the frontal three solutions,
      while LXT-101 in pure water maintained over a period of 7 days. CONCLUSIONS: It
      may indicate that LXT-101 peptide in pure water forms fibre depot that release
      monomeric active peptide slowly. The correlation between the nanostructure and
      duration of action in vivo suggests that the addition of excipients influence
      self-assembly process of LXT-101 that leads to the formation of different
      nanostructures and exhibit various behaviours in vivo.

PMID- 24579974
TI  - Measurements and modeling of deposited particle transport by foot traffic
      indoors.
AB  - Deposited particles are transported into and within buildings by adhering to and
      releasing from people's shoes. To better understand transport of deposited
      particulate contaminants and exposures to these materials, experimental data on
      tracking by foot traffic are needed. Laboratory experiments measured uptake and
      downlay mass transfer efficiencies of particles between shoes and floors in a
      step-simulation chamber. Equilibrium uptake transfer fractions, the net mass
      fraction transferred from floors to shoes after several steps, were also
      measured. Single-step uptake and downlay transfer efficiencies ranged from 0.02
      to 0.22 and equilibrium uptake transfer fractions were 0.10-0.40. Particle size,
      particle loading, shoe type, floor type, step pressure, and step sequence were
      all investigated. Experiments demonstrated that single-step downlay transfer
      efficiencies decrease with each successive step onto clean floors. A simple
      empirical model is proposed to estimate these transfers as a function of step
      number. Simulations using the transfer efficiency values measured here illustrate
      the spread of deposited particles by people walking in a hypothetical hallway.
      These simulations show that in locations where a few people walk over the same
      area each minute, tracking can spread deposited material over length scales
      comparable to building dimensions in just a few hours. 

PMID- 24579972
TI  - De novo mutation in the NOTCH3 gene causing CADASIL.
AB  - Cerebral autosomal dominant arteriopathy with subcortical infarcts and
      leucoencephalopathy (CADASIL) is one of the most common hereditary forms of
      stroke, and migraine with aura, mood disorders and dementia. CADASIL is caused by
      mutations of the NOTCH3 gene. This mutation is inherited as an autosomal dominant
      trait. Most individuals with CADASIL have a parent with the disorder. In
      extremely rare cases, CADASIL may occur due to a spontaneous genetic mutation
      that occurs for unknown reasons (de novo mutation). We report a new case of
      patient with de novo mutation of the NOTCH3 gene and a condition strongly
      suggestive of CADASIL (migraine, stroke, and white matter abnormalities), except
      that this patient did not have any first-degree relatives with similar symptoms. 

PMID- 24579975
TI  - Bacterial community composition of divergent soil habitats in a polar desert.
AB  - Edaphic factors such as pH, organic matter, and salinity are often the most
      significant drivers of diversity patterns in soil bacterial communities. Desert
      ecosystems in particular are model locations for examining such relationships as
      food web complexity is low and the soil environment is biogeochemically
      heterogeneous. Here, we present the findings from a 16S rRNA gene sequencing
      approach used to observe the differences in diversity and community composition
      among three divergent soil habitats of the McMurdo Dry Valleys, Antarctica.
      Results show that alpha diversity is significantly lowered in high pH soils,
      which contain higher proportions of the phyla Acidobacteria and Actinobacteria,
      while mesic soils with higher soil organic carbon (and ammonium) content contain
      high proportions of Nitrospira, a nitrite-oxidizing bacteria. Taxonomic community
      resolution also had a significant impact on our conclusions, as pH was the
      primary predictor of phylum-level diversity, while moisture was the most
      significant predictor of diversity at the genus level. Predictive power also
      increased with increasing taxonomic resolution, suggesting a potential increase
      in niche-based drivers of bacterial community composition at such levels. 

PMID- 24579976
TI  - Improvement of language functions in a chronic non-fluent post-stroke aphasic
      patient following bilateral sequential theta burst magnetic stimulation.
AB  - In chronic non-fluent aphasia patients, inhibition of the intact right hemisphere
      (RH), by transcranial magnetic stimulation (TMS) or similar methods, can induce
      improvement in language functions. The supposed mechanism behind this improvement
      is a release of preserved left hemisphere (LH) language networks from RH
      transcallosal inhibition. Direct stimulation of the damaged LH can sometimes
      bring similar results too. Therefore, we developed a novel treatment approach
      that combined direct LH (Broca's area (BA)) stimulation, by intermittent theta
      burst stimulation (TBS), with homologue RH area's inhibition, by continuous TBS.
      We present the results of application of 15 daily sessions of the described
      treatment approach in a right-handed patient with chronic post-stroke non-fluent
      aphasia. The intervention appeared to improve several language functions, but
      most notably propositional speech, semantic fluency, short-term verbal memory,
      and verbal learning. Bilateral TBS modulation of activation of the language
      related areas of both hemispheres seems to be a feasible and promising way to
      induce recovery in chronic aphasic patients. Due to potentially cumulative
      physiological effects of bilateral stimulation, the improvements may be even
      greater than following unilateral interventions. 

PMID- 24579977
TI  - The total syntheses of guttiferone A and 6-epi-guttiferone A.
AB  - Polyprenylated polycyclic acylphloroglucinols (PPAP) are a constantly growing
      class of natural products that exhibit a common bicyclo[3.3.1]nonatrione core and
      consist of currently more than 200 members. A subclassification among the various
      natural products of this class includes the position of the exocyclic acyl group,
      the prenylation grade of the core, and the relative configuration at C-7 within
      the core. About 10% of the reported structures, however, possess an additional
      chiral center at C-6. Herein we describe a straightforward access to guttiferone
      A and epi-guttiferone A, in which full control of stereoselectivity is achieved
      via conformational control, and a strict separation of framework decorating from
      framework constructing operations sets the stage for a short 13-step synthesis. 

PMID- 24579978
TI  - High-throughput sequencing for the identification of NOTCH1 mutations in early
      stage chronic lymphocytic leukaemia: biological and clinical implications.
AB  - NOTCH1 mutations have recently emerged as new genetic lesions significantly
      correlated with survival in chronic lymphocytic leukaemia (CLL). We performed
      deep next generation sequencing of the NOTCH1 mutation hotspot in 384 cases at
      diagnosis, including 100 monoclonal B cell lymphocytosis (MBL) and 284 Binet
      stage A CLL cases, enrolled in the Gruppo Italiano Studio Linfomi O-CLL1
      multicentre trial. The NOTCH1 c.7541_7542delCT dinucleotide deletion was detected
      and confirmed by an extremely sensitive polymerase chain reaction-based approach
      in 11% of MBL and 13.4% of CLL patients. Remarkably, the NOTCH1 mutation was
      often observed at low clonal level, mainly in MBL patients. Sequential analyses
      in a fraction of cases showed that the NOTCH1 mutation generally does not occur
      during the disease course and that the mutational load in positive cases tends to
      be stable over time. NOTCH1-mutated cases, even at low clonal level, displayed a
      significant reduction in median progression-free survival, although NOTCH1
      mutation lost its prognostic impact in a multivariate analysis including 11q
      and/or 17p deletion, IGHV mutational status, and MBL or CLL status. Our data
      highlight the importance of using highly sensitive methods to measure NOTCH1
      mutations, in order to improve prognostic stratification and obtain useful
      information for potential therapeutic approaches. 

PMID- 24579979
TI  - Express immunochromatographic detection of antibodies against Brucella abortus in
      cattle sera based on quantitative photometric registration and modulated cut-off
      level.
AB  - An immunochromatographic test system was developed for rapid detection of the
      levels of specific IgG antibodies to Brucella abortus lipopolysaccharide, as a
      tool for diagnosis of brucellosis in cattle. The pilot test strips were examined
      using blood sera from sick (78 samples) and healthy (35 samples) cows. The
      results obtained by immunochromatographic assay, using a portable optical
      densitometer for digital video detection, correlate well with the results
      obtained by immunoenzyme assay and are in agreement with the results of the
      disease diagnosis. The new test system allows detection of antibodies within 10
      min and can be proposed as an alternative to the methods available for
      serodiagnosis of brucellosis. 

PMID- 24579981
TI  - Rational design of inverted nanopencil arrays for cost-effective, broadband, and
      omnidirectional light harvesting.
AB  - Due to the unique optical properties, three-dimensional arrays of silicon
      nanostructures have attracted increasing attention as the efficient photon
      harvesters for various technological applications. In this work, instead of dry
      etching, we have utilized our newly developed wet anisotropic etching to
      fabricate silicon nanostructured arrays with different well-controlled
      geometrical morphologies, ranging from nanopillars, nanorods, and inverted
      nanopencils to nanocones, followed by systematic investigations of their photon
      capturing properties combining experiments and simulations. It is revealed that
      optical properties of these nanoarrays are predominantly dictated by their
      geometrical factors including the structural pitch, material filling ratio, and
      aspect ratio. Surprisingly, along with the proper geometrical design, the
      inverted nanopencil arrays can couple incident photons into optical modes in the
      pencil base efficiently in order to achieve excellent broadband and
      omnidirectional light-harvesting performances even with the substrate thickness
      down to 10 MUm, which are comparable to the costly and technically difficult to
      achieve nanocone counterparts. Notably, the fabricated nanopencils with both 800
      and 380 nm base diameters can suppress the optical reflection well below 5% over
      a broad wavelength of 400-1000 nm and a wide angle of incidence between 0 and 60
      degrees . All these findings not only offer additional insight into the light
      trapping mechanism in these complex 3D nanophotonic structures but also provide
      efficient broadband and omnidirectional photon harvesters for next-generation
      cost-effective ultrathin nanostructured photovoltaics. 

PMID- 24579982
TI  - Autosomal dominant partial epilepsy with auditory features: a new locus on
      chromosome 19q13.11-q13.31.
AB  - OBJECTIVE: To clinically and genetically characterize a large Brazilian family
      with autosomal dominant partial epilepsy with auditory features (ADPEAF) not
      related to leucine-rich, glioma-inactivated 1 (LGI1) gene. METHODS: Seventy
      family members (four married-ins) participating in the study were assessed by a
      detailed clinical interview and a complete neurologic examination. Genetic
      mapping was conducted through autosome-wide single nucleotide polymorphism (SNP)
      genotyping and subsequent linkage analysis on 16 and haplotype analysis on 25
      subjects, respectively. RESULTS: The pedigree comprised 15 affected members, of
      whom 11 were included in the study (male/female: 6/5; mean age 39.5 years). All
      but two (III:22 and IV:92) had focal seizures with auditory aura followed by
      secondary generalization in 44.4%. The mean age at onset of epilepsy seizures was
      13.7 years. Initial autosome-wide SNP linkage analysis conducted on 12 subjects
      (8 affected) pointed to a single genomic region on chromosome 19 with a maximum
      multipoint logarithm of the odds (LOD) score of 2.60. Further refinement of this
      region through SNP and microsatellite genotyping on 16 subjects (11 affected)
      increased the LOD score to 3.41, thereby establishing 19q13.11-q13.31 as a novel
      ADPEAF locus. Haplotype analysis indicated that the underlying mutation is most
      likely located in a 9.74 Mb interval between markers D19S416 and D19S420.
      Sequence analysis of the most prominent candidate genes within this critical
      interval (SCN1B, LGI4, KCNK6, and LRFN1) did not reveal any mutation.
      SIGNIFICANCE: This study disclosed a novel ADPEAF locus on chromosome 19q13.11
      q13.31, contributing to future identification of a second dominant gene for this
      epileptic syndrome. A PowerPoint slide summarizing this article is available for
      download in the Supporting Information section here.

PMID- 24579980
TI  - Interpersonal guilt and substance use in college students.
AB  - BACKGROUND: The college years are a time for developing independence and
      separating from one's family, and they are also a time in which substance use
      often escalates. This study examined the relationships between use of substances
      and interpersonal guilt, an emotion that can arise from feelings about separation
      among college students. METHODS: In total, 1865 college students completed a
      survey evaluating substance use and interpersonal guilt. Regular users of
      alcohol, cigarettes, cannabis, and other illicit drugs were compared with
      nonregular users of each substance. Sequential linear regression, controlling for
      confounding variables, examined relationships between regular use of each
      substance and scores on a guilt index. RESULTS: Risky drinkers and daily smokers
      had significantly more interpersonal guilt than their peers who did not regularly
      use these substances. In contrast, regular cannabis users had significantly less
      guilt than nonregular cannabis users. CONCLUSIONS: These data suggest that
      substance use among college students may be related to interpersonal guilt and
      family separation issues, and this relationship may vary across substances.

PMID- 24579983
TI  - Castor bean seed ingestions: a state-wide poison control system's experience.
AB  - CONTEXT: Ingestions of the seed of the castor bean plant (Ricinus communis)
      carries the risk of toxicity from ricin, a potent inhibitor of protein synthesis.
      OBJECTIVE: We sought to describe characteristics of castor bean seed exposures
      reported to a state-wide poison control system. METHODS: This was an
      observational case series. A state-wide poison control system's database was
      reviewed for exposures to castor bean plant seeds from 2001 to 2011. Case notes
      were reviewed and data collected, when available, included age, gender,
      circumstances surrounding exposure, number of castor beans consumed, whether
      beans were chewed or crushed, symptoms described, laboratory values (aspartate
      aminotransferase [AST], alanine aminotransferase [ALT], prothrombin time [PT] and
      international normalized ratio [INR]), duration of follow-up, treatment, and
      patient outcomes. RESULTS: Eighty-four cases were identified. Ingestions were
      unintentional in 50 cases (59%) cases and intentional in 34 (40%) cases. A median
      of 10 seeds (range: 1-20) were ingested in intentional cases versus 1 seed
      (range: 1-40) in unintentional cases. In 49 (58%) of cases the seeds were
      reported to have been chewed or crushed. Gastrointestinal symptoms were the most
      commonly reported symptoms. Vomiting (n = 39), nausea (n = 24), diarrhea (n =
      17), and abdominal pain (n = 16) predominated. One patient developed hematochezia
      and vomiting after reportedly ingesting and intravenously injecting castor bean
      seeds. Laboratory values were documented in 17 (20%) cases. Only one abnormality
      was noted; an asymptomatic patient one week following ingestion had AST/ALT of 93
      U/L and 164 U/L, respectively. Ricinine was confirmed in the urine of two
      patients. Twenty-three (27%) cases received activated charcoal. Seventy-two (86%)
      of cases were calls from health care facilities or referred to health care
      facilities by the poison control center. Twenty-two (26%) cases were admitted for
      a median of 2 days (range: 1-10). Admitted cases ingested a median of 8.5 seeds
      (range: 1-20). Intentional ingestions were followed for median of 37.5 h (range:
      0.5-285.5) while unintentional cases were followed for 14 h (range: 1-182). No
      delayed symptoms, serious outcomes, or deaths were reported. DISCUSSION: Due to
      the presence of ricin, there is concern for serious outcomes after ingestions of
      the seeds of the castor bean plant. In this study GI symptoms were most commonly
      reported but serious morbidity or mortality was not present. The true risk of
      castor bean plant seed ingestions should continue to be re-evaluated. CONCLUSION:
      In this retrospective review, gastrointestinal symptoms were the most common
      symptoms described after reported exposures to castor bean seeds. These exposures
      were not associated with serious morbidity, mortality, or delayed symptoms.

PMID- 24579984
TI  - Talking about friends, drugs, and change: meanings of friendship in substance
      abusers' change talk.
AB  - This article explores the meanings of substance-abusing clients attach to
      friendships during motivational treatment sessions in Probation Service. Sessions
      (98) were videotaped in 12 probation service offices in Finland in 2007 to 2009.
      By using semiotic framework, this qualitative study examines client's change talk
      utterance about friendships as a symbolic sign. The findings indicate that the
      friendships play an important role in the substance-abusing clients' motivation
      to change and in their treatment outcome. The study suggests that the personal
      meanings of clients' utterances in motivational treatment sessions could be seen
      as potential predictors of their future behavior. 

PMID- 24579985
TI  - Three-dimensional structure of P3HT assemblies in organic solvents revealed by
      cryo-TEM.
AB  - Poly(3-hexylthiophene) (P3HT) assemblies in vitrified organic solvents were
      visualized at nanometer scale resolution by cryo-transmission electron
      microscopy, low dose electron diffraction, and cryo-tomography revealing a three
      dimensional lamellar structure formed by the stacking of the conjugated backbones
      of P3HT with a distance of 1.7 nm and increased order in the bulk of the
      nanowire. This combination of techniques reveals local structures in dispersion
      and the condensed state that play a crucial role in the performance of organic
      electronic devices. 

PMID- 24579987
TI  - The Nobori biolimus-eluting stent: update of available evidence.
AB  - Despite first-generation drug-eluting stents (DES) dramatically reduced the need
      for repeat revascularization in patients undergoing percutaneous coronary
      intervention, their use was associated with an increased risk of thrombotic
      events at long-term follow-up. The Nobori biolimus-eluting stent (BES) is a
      second-generation DES with a biodegradable poly-lactic acid polymer. During the
      last few years, several randomized trials have compared the Nobori BES with other
      DES, making this device the most investigated biodegradable DES. In this article,
      we reviewed current available data about Nobori BES from pharmacokinetic and
      observational studies to randomized clinical trials.

PMID- 24579986
TI  - Does perceived risk influence the effects of message framing? A new investigation
      of a widely held notion.
AB  - Health-promoting messages can be framed in terms of the beneficial consequences
      of healthy behaviour (gain-framed messages) or the detrimental consequences of
      unhealthy behaviour (loss-framed messages). An influential notion holds that the
      perceived risk associated with the recommended behaviour determines the relative
      persuasiveness of gain- and loss-framed messages. This 'risk-framing hypothesis',
      as we call it, was derived from prospect theory, has been central to health
      message framing research for the last two decades, and does not cease to appeal
      to researchers. The present paper examines the validity of the risk-framing
      hypothesis. We performed six empirical studies on the interaction between
      perceived risk and message framing. These studies were conducted in two different
      countries and employed framed messages targeting skin cancer prevention and
      detection, physical activity, breast self-examination and vaccination behaviour.
      Behavioural intention served as the outcome measure. None of these studies found
      evidence in support of the risk-framing hypothesis. We conclude that the
      empirical evidence in favour of the hypothesis is weak and discuss the
      ramifications of this for future message framing research. 

PMID- 24579988
TI  - The diversity, biogenesis, and activities of endogenous silencing small RNAs in
      Arabidopsis.
AB  - In eukaryotic RNA silencing, RNase-III classes of enzymes in the Dicer family
      process double-stranded RNA of cellular or exogenous origin into small-RNA (sRNA)
      molecules. sRNAs are then loaded into effector proteins known as ARGONAUTEs
      (AGOs), which, as part of RNA-induced silencing complexes, target complementary
      RNA or DNA for silencing. Plants have evolved a large variety of pathways over
      the Dicer-AGO consortium, which most likely underpins part of their phenotypic
      plasticity. Dicer-like proteins produce all known classes of plant silencing
      sRNAs, which are invariably stabilized via 2'-O-methylation mediated by HUA
      ENHANCER 1 (HEN1), potentially amplified by the action of several RNA-dependent
      RNA polymerases, and function through a variety of AGO proteins. Here, we review
      the known characteristics and biochemical properties of the core silencing
      factors found in the model plant Arabidopsis thaliana. We also describe how
      interactions between these core factors and more specialized proteins allow the
      production of a plethora of silencing sRNAs involved in a large array of
      biological functions. We emphasize in particular the biogenesis and activities of
      silencing sRNAs of endogenous origin. 

PMID- 24579989
TI  - Engineering complex metabolic pathways in plants.
AB  - Metabolic engineering can be used to modulate endogenous metabolic pathways in
      plants or introduce new metabolic capabilities in order to increase the
      production of a desirable compound or reduce the accumulation of an undesirable
      one. In practice, there are several major challenges that need to be overcome,
      such as gaining enough knowledge about the endogenous pathways to understand the
      best intervention points, identifying and sourcing the most suitable metabolic
      genes, expressing those genes in such a way as to produce a functional enzyme in
      a heterologous background, and, finally, achieving the accumulation of target
      compounds without harming the host plant. This article discusses the strategies
      that have been developed to engineer complex metabolic pathways in plants,
      focusing on recent technological developments that allow the most significant
      bottlenecks to be overcome. 

PMID- 24579990
TI  - Sucrose metabolism: gateway to diverse carbon use and sugar signaling.
AB  - Sucrose metabolism plays pivotal roles in development, stress response, and yield
      formation, mainly by generating a range of sugars as metabolites to fuel growth
      and synthesize essential compounds (including protein, cellulose, and starch) and
      as signals to regulate expression of microRNAs, transcription factors, and other
      genes and for crosstalk with hormonal, oxidative, and defense signaling. This
      review aims to capture the most exciting developments in this area by evaluating
      (a) the roles of key sucrose metabolic enzymes in development, abiotic stress
      responses, and plant-microbe interactions; (b) the coupling between sucrose
      metabolism and sugar signaling from extra- to intracellular spaces; (c) the
      different mechanisms by which sucrose metabolic enzymes could perform their
      signaling roles; and (d) progress on engineering sugar metabolism and transport
      for high yield and disease resistance. Finally, the review outlines future
      directions for research on sugar metabolism and signaling to better understand
      and improve plant performance. 

PMID- 24579991
TI  - Phosphate nutrition: improving low-phosphate tolerance in crops.
AB  - Phosphorus is an essential nutrient that is required for all major developmental
      processes and reproduction in plants. It is also a major constituent of the
      fertilizers required to sustain high-yield agriculture. Levels of phosphate--the
      only form of phosphorus that can be assimilated by plants--are suboptimal in most
      natural and agricultural ecosystems, and when phosphate is applied as fertilizer
      in soils, it is rapidly immobilized owing to fixation and microbial activity.
      Thus, cultivated plants use only approximately 20-30% of the applied phosphate,
      and the rest is lost, eventually causing water eutrophication. Recent advances in
      the understanding of mechanisms by which wild and cultivated species adapt to low
      phosphate stress and the implementation of alternative bacterial pathways for
      phosphorus metabolism have started to allow the design of more effective breeding
      and genetic engineering strategies to produce highly phosphate-efficient crops,
      optimize fertilizer use, and reach agricultural sustainability with a lower
      environmental cost. In this review, we outline the current advances in research
      on the complex network of plant responses to low-phosphorus stress and discuss
      some strategies used to manipulate genes involved in phosphate uptake,
      remobilization, and metabolism to develop low-phosphate-tolerant crops, which
      could help in designing more efficient crops.

PMID- 24579992
TI  - Cyanogenic glycosides: synthesis, physiology, and phenotypic plasticity.
AB  - Cyanogenic glycosides (CNglcs) are bioactive plant products derived from amino
      acids. Structurally, these specialized plant compounds are characterized as alpha
      hydroxynitriles (cyanohydrins) that are stabilized by glucosylation. In recent
      years, improved tools within analytical chemistry have greatly increased the
      number of known CNglcs by enabling the discovery of less abundant CNglcs formed
      by additional hydroxylation, glycosylation, and acylation reactions. Cyanogenesis
      -the release of toxic hydrogen cyanide from endogenous CNglcs--is an effective
      defense against generalist herbivores but less effective against fungal
      pathogens. In the course of evolution, CNglcs have acquired additional roles to
      improve plant plasticity, i.e., establishment, robustness, and viability in
      response to environmental challenges. CNglc concentration is usually higher in
      young plants, when nitrogen is in ready supply, or when growth is constrained by
      nonoptimal growth conditions. Efforts are under way to engineer CNglcs into some
      crops as a pest control measure, whereas in other crops efforts are directed
      toward their removal to improve food safety. Given that many food crops are
      cyanogenic, it is important to understand the molecular mechanisms regulating
      cyanogenesis so that the impact of future environmental challenges can be
      anticipated.

PMID- 24579993
TI  - Plant molecular pharming for the treatment of chronic and infectious diseases.
AB  - Plant molecular pharming has emerged as a niche technology for the manufacture of
      pharmaceutical products indicated for chronic and infectious diseases,
      particularly for products that do not fit into the current industry-favored model
      of fermenter-based production campaigns. In this review, we explore the areas
      where molecular pharming can make the greatest impact, including the production
      of pharmaceuticals that have novel glycan structures or that cannot be produced
      efficiently in microbes or mammalian cells because they are insoluble or toxic.
      We also explore the market dynamics that encourage the use of molecular pharming,
      particularly for pharmaceuticals that are required in small amounts (such as
      personalized medicines) or large amounts (on a multi-ton scale, such as blood
      products and microbicides) and those that are needed in response to emergency
      situations (pandemics and bioterrorism). The impact of molecular pharming will
      increase as the platforms become standardized and optimized through adoption of
      good manufacturing practice (GMP) standards for clinical development, offering a
      new opportunity to produce inexpensive medicines in regional markets that are
      typically excluded under current business models. 

PMID- 24579994
TI  - Genetically engineered crops: from idea to product.
AB  - Genetically engineered crops were first commercialized in 1994 and since then
      have been rapidly adopted, enabling growers to more effectively manage pests and
      increase crop productivity while ensuring food, feed, and environmental safety.
      The development of these crops is complex and based on rigorous science that must
      be well coordinated to create a plant with desired beneficial phenotypes. This
      article describes the general process by which a genetically engineered crop is
      developed from an initial concept to a commercialized product. 

PMID- 24579995
TI  - Molecular control of cell specification and cell differentiation during
      procambial development.
AB  - Land plants develop vascular tissues that enable the long-distance transport of
      water and nutrients in xylem and phloem, provide mechanical support for their
      vertical growth, and produce cells in radial growth. Vascular tissues are
      produced in many parts of the plant and during different developmental stages.
      Early vascular development is focused in procambial meristems, and in some
      species it continues during the secondary phase of plant development in cambial
      meristems. In this review, we highlight recent progress in understanding
      procambial development. This involves the analysis of stem cell-like properties
      of procambial tissues, specification of xylem and phloem, and differentiation of
      the conductive tissues. Several major plant hormones, small-RNA species, and
      transcriptional networks play a role in vascular development. We describe current
      approaches to integrating these networks as well as their potential role in
      explaining the diversity and evolution of plant vascular systems. 

PMID- 24579996
TI  - The contributions of transposable elements to the structure, function, and
      evolution of plant genomes.
AB  - Transposable elements (TEs) are the key players in generating genomic novelty by
      a combination of the chromosome rearrangements they cause and the genes that come
      under their regulatory sway. Genome size, gene content, gene order, centromere
      function, and numerous other aspects of nuclear biology are driven by TE
      activity. Although the origins and attitudes of TEs have the hallmarks of selfish
      DNA, there are numerous cases where TE components have been co-opted by the host
      to create new genes or modify gene regulation. In particular, epigenetic
      regulation has been transformed from a process to silence invading TEs and
      viruses into a key strategy for regulating plant genes. Most, perhaps all, of
      this epigenetic regulation is derived from TE insertions near genes or TE-encoded
      factors that act in trans. Enormous pools of genome data and new technologies for
      reverse genetics will lead to a powerful new era of TE analysis in plants. 

PMID- 24579997
TI  - The cell biology of cellulose synthesis.
AB  - Plant stature and development are governed by cell proliferation and directed
      cell growth. These parameters are determined largely by cell wall
      characteristics. Cellulose microfibrils, composed of hydrogen-bonded beta-1,4
      glucans, are key components for anisotropic growth in plants. Cellulose is
      synthesized by plasma membrane-localized cellulose synthase complexes. In higher
      plants, these complexes are assembled into hexameric rosettes in intracellular
      compartments and secreted to the plasma membrane. Here, the complexes typically
      track along cortical microtubules, which may guide cellulose synthesis, until the
      complexes are inactivated and/or internalized. Determining the regulatory aspects
      that control the behavior of cellulose synthase complexes is vital to
      understanding directed cell and plant growth and to tailoring cell wall content
      for industrial products, including paper, textiles, and fuel. In this review, we
      summarize and discuss cellulose synthesis and regulatory aspects of the cellulose
      synthase complex, focusing on Arabidopsis thaliana. 

PMID- 24579998
TI  - Early hospital readmissions post-kidney transplantation are associated with
      inferior clinical outcomes.
AB  - Unplanned hospital readmissions are common early post-kidney transplantation. We
      investigated the relationship between early hospital readmissions and clinical
      outcomes in a single-center retrospective study that included all adult kidney
      transplant patients between 2004 and 2008 with follow-up to December 2012. The
      early hospital readmissions within the first 30 d were numbered and the diagnosis
      ascertained. Patients were grouped as none, once, and twice or more readmissions.
      Predictors of early readmissions were assessed, and clinical outcomes and patient
      and death-censored kidney survival were compared. Among 1064 patients, 203
      (19.1%) patients had once and 83 (7.8%) patients had twice or more readmissions
      within 30 d. Surgical complications, infections, and acute kidney injuries/acute
      rejection were three most common diagnoses. The length of initial hospital stay
      and African American race were among the variables associated significantly with
      readmissions. Patients with early readmissions had lower baseline renal function
      (p < 0.01) and more early acute rejection (p < 0.01). During follow-up, only
      frequent readmissions, twice or more, within 30 d were associated with increased
      risk of death (AHR 1.75, p = 0.01) and death-censored kidney failure (AHR 2.20, p
      < 0.01). Frequent early hospital readmissions post-transplantation identify
      patients at risk for poor long-term outcomes, and more studies are needed to
      understand the mechanisms. 

PMID- 24579999
TI  - Effects of varying fixed lingual apex positions on tongue pressure during straw
      drinking.
AB  - We investigated the impact of tongue-thrusting on lingual pressure during fluid
      intake with a straw. In this study, 12 healthy young dentate individuals (two
      women and 10 men; 19-33 years) were instructed to drink 15 mL of water with a
      regular drinking straw at 37  degrees C, when indicated by the investigator.
      Participants drank after adjusting tongue position to one of the following
      patterns: (i) Holding the tip of the straw between the lips (Normal Position:
      NP), (ii) Sticking out the tongue to the vermilion zone of the lower lip and
      inserting the straw 1 cm past the front teeth (Tongue-thrusting Position: TP).
      Five recordings were conducted for each participant in a randomised order. To
      measure tongue pressure during swallowing, a specially designed 0.1-mm thick
      sensor sheet (Nitta, Osaka, Japan) with a tactile system for measurement of
      pressure distribution (I-SCAN; Nitta) was used. Duration, maximal magnitude and
      integrated value of tongue pressure were analysed based on the wave of tongue
      pressure recorded while water was swallowed. Magnitude, duration and integrated
      value of tongue pressure were significantly lower in TP than in NP at the median
      line (Ch1-3). Magnitude and integrated value of tongue pressure at the lateral
      part of the tongue (Ch5) were significantly lower in TP than in NP. When
      duration, maximal magnitude and integrated values were compared by channel, no
      significant differences were observed in NP, but a significant difference was
      found between Ch3 and the lateral areas Ch4/Ch 5 in TP. When the tongue was
      thrust forward, movement dynamics of the entire tongue changed and influenced
      contact between the tongue and palate during liquid intake with a straw. The
      impact was noticeably weaker on the median line than in lateral areas.

PMID- 24580001
TI  - Clinical and radiographic outcomes of minimally invasive percutaneous pedicle
      screw placement with intraoperative CT (O-arm) image guidance navigation.
AB  - OBJECT: Intraoperative CT image-guided navigation (IGN) has been increasingly
      incorporated into minimally invasive spine surgery (MIS). The vast improvement in
      image resolution and virtual real-time images with CT-IGN has proven superiority
      over traditional fluoroscopic techniques. The authors describe their
      perioperative MIS technique using the O-arm with navigation, and they report
      their postoperative experience, accuracy results, and technical aspects. METHODS:
      A retrospective review of 48 consecutive adult patients undergoing minimally
      invasive percutaneous posterior spinal fusion with intraoperative CT-IGN between
      July 2010 and August 2013 at Cedars-Sinai Medical Center was performed. Two
      surgeons assessed 290 screws in a blinded fashion on intraoperative O-arm images
      and postoperative CT scans for bony pedicle wall breach. Grade 1 breach was
      defined to be < 2 mm, Grade 2 breach to be between 2 and 4 mm, and a Grade 3
      breach to be > 4 mm. Additionally, anterior vertebral body breach was recorded.
      RESULTS: Of 290 pedicle screws placed, 280 (96.6%) were in an acceptable position
      without cortical wall or anterior breach. Of the 10 breaches (3.4%) 5 were
      lateral (50%), 4 were medial, and 1 was anterior; 90% of breaches were Grade 1-2
      and all medial breaches were Grade 1. The one Grade 3 breach was lateral. No
      vascular or neurological complications were observed intraoperatively, and no
      significant postoperative complications were noted. The mean clinical follow-up
      period was 18 months (range 3-39 months). The overall clinical outcomes, measured
      using the visual analog scale (back pain scores), were improved significantly
      postoperatively at 3 months compared with preoperatively (visual analog score
      6.35 vs 3.57; p < 0.0001). No revision surgery was performed for screw
      misplacement or neurological deterioration. CONCLUSIONS: New CT-IGN with the
      mobile O-arm scanner has increased the accuracy of pedicle screw/instrumentation
      placement using MIS techniques. The authors' high (96.6%) accuracy rate in MIS
      compares favorably with historical published accuracy rates for fluoroscopy-based
      techniques. Additional advantages of CT-IGN over fluoroscopic imaging methods are
      lower occupational radiation exposure for the surgical team, reduced need for
      postoperative imaging, and decreased rates of revision surgery. For now, the
      authors simply conclude that use of intraoperative CT-IGN is safe and accurate.

PMID- 24580002
TI  - Robotics and the spine: a review of current and ongoing applications.
AB  - OBJECT: Robotics in the operating room has shown great use and versatility in
      multiple surgical fields. Robot-assisted spine surgery has gained significant
      favor over its relatively short existence, due to its intuitive promise of higher
      surgical accuracy and better outcomes with fewer complications. Here, the authors
      analyze the existing literature on this growing technology in the era of
      minimally invasive spine surgery. METHODS: In an attempt to provide the most
      recent, up-to-date review of the current literature on robotic spine surgery, a
      search of the existing literature was conducted to obtain all relevant studies on
      robotics as it relates to its application in spine surgery and other
      interventions. RESULTS: In all, 45 articles were included in the analysis. The
      authors discuss the current status of this technology and its potential in
      multiple arenas of spinal interventions, mainly spine surgery and spine
      biomechanics testing. CONCLUSIONS: There are numerous potential advantages and
      limitations to robotic spine surgery, as suggested in published case reports and
      in retrospective and prospective studies. Randomized controlled trials are few in
      number and show conflicting results regarding accuracy. The present limitations
      may be surmountable with future technological improvements, greater surgeon
      experience, reduced cost, improved operating room dynamics, and more training of
      surgical team members. Given the promise of robotics for improvements in spine
      surgery and spine biomechanics testing, more studies are needed to further
      explore the applicability of this technology in the spinal operating room. Due to
      the significant cost of the robotic equipment, studies are needed to substantiate
      that the increased equipment costs will result in significant benefits that will
      justify the expense.

PMID- 24580003
TI  - Accuracy of intraoperative computed tomography image-guided surgery in placing
      pedicle and pelvic screws for primary versus revision spine surgery.
AB  - OBJECT: Revision spine surgery, which is challenging due to disrupted anatomy,
      poor fluoroscopic imaging, and altered tactile feedback, may benefit from CT
      image-guided surgery (CT-IGS). This study evaluates accuracy of CT-IGS-navigated
      screws in primary versus revision spine surgery. METHODS: Pedicle and pelvic
      screws placed with the O-arm in 28 primary (313 screws) and 33 revision (429
      screws) cases in which institutional postoperative CT scans were available were
      retrospectively reviewed for placement accuracy. Screw accuracy was categorized
      as 1) good (< 1-mm pedicle breach in any direction or "in-out-in" thoracic screws
      through the lateral thoracic pedicle wall and in the costovertebral joint); 2)
      fair (1- to 3-mm breach); or 3) poor (> 3-mm breach). RESULTS: Use of CT-IGS
      resulted in high rates of good or fair screws for both primary (98.7%) and
      revision (98.6%) cases. Rates of good or fair screws were comparable for the
      following regions: C7-T3 at 100% (good or fair) in primary versus 100% (good or
      fair) in revision; T4-9 at 96.8% versus 100%; T10-L2 at 98.2% versus 99.3%; L3-5
      at 100% versus 99.2%; and pelvis at 98.7% versus 98.6%, respectively. On the
      other hand, revision sacral screws had statistically significantly lower rates of
      good placement compared with primary (100% primary vs 80.6% revision, p = 0.027).
      Of these revision sacral screws, 11.1% had poor placement, with bicortical screws
      extending > 3 mm beyond the anterior cortex. Revision pelvic screws demonstrated
      the highest rate of fair placement (28%), with the mode of medial breach in all
      cases directed into the sacral-iliac joint. CONCLUSIONS: In the cervical,
      thoracic, and lumbar spine, CT-IGS demonstrated comparable accuracy rates for
      both primary and revision spine surgery. Use of 3D imaging of the bony pedicle
      anatomy appears to be sufficient for the spine surgeon to overcome the
      difficulties associated with instrumentation in revision cases. Although the bony
      structures of sacral pedicles and pelvis are relatively larger, the complexity of
      local anatomy was not overcome with CT-IGS, and an increased trend toward
      inaccurate screw placement was demonstrated.

PMID- 24580004
TI  - Intraoperative image-guided spinal navigation: technical pitfalls and their
      avoidance.
AB  - Spinal instrumentation has made significant advances in the last two decades,
      with transpedicular constructs now widely used in spinal fixation. Pedicle screw
      constructs are routinely used in thoracolumbar-instrumented fusions, and in
      recent years, the cervical spine as well. Three-column fixations with pedicle
      screws provide the most rigid form of posterior stabilization. Surgical landmarks
      and fluoroscopy have been used routinely for pedicle screw insertion, but a
      number of studies reveal inaccuracies in placement using these conventional
      techniques (ranging from 10% to 50%). The ability to combine 3D imaging with
      intraoperative navigation systems has improved the accuracy and safety of pedicle
      screw placement, especially in more complex spinal deformities. However, in the
      authors' experience with image guidance in more than 1500 cases, several
      potential pitfalls have been identified while using intraoperative spinal
      navigation that could lead to suboptimal results. This article summarizes the
      authors' experience with these various pitfalls using spinal navigation, and
      gives practical tips on their avoidance and management.

PMID- 24580005
TI  - Experience with intraoperative navigation and imaging during endoscopic
      transnasal spinal approaches to the foramen magnum and odontoid.
AB  - OBJECT: In this study the authors share their experience using intraoperative
      spinal navigation and imaging for endoscopic transnasal approaches to the
      odontoid in 5 patients undergoing C1-2 surgery for basilar invagination at
      Stanford Hospital and Clinics from 2010 to 2013. METHODS: Of these 5 patients
      undergoing C1-2 surgery for basilar invagination, 4 underwent a 2-tiered anterior
      C1-2 resection with posterior occipitocervical fusion during a first stage
      surgery, followed by endoscopic endonasal odontoidectomy in a separate setting.
      Intraoperative stereotactic navigation was performed using a surgical navigation
      system in all cases. Navigation accuracy, characterized as target registration
      error, ranged between 0.8 mm and 2 mm, with an average of 1.2 mm. Intraoperative
      imaging using a CT scanner was also performed in 2 patients. RESULTS: Endoscopic
      decompression of the brainstem was achieved in all patients, and no
      intraoperative complications were encountered. All patients were extubated within
      24 hours after surgery and were able to swallow within 48 hours. After
      appropriate initial reconstruction of the defect at the craniocervical junction,
      no postoperative CSF leakage, arterial injury, or need for reoperation was
      encountered; 1 patient developed mild postoperative velopharyngeal insufficiency
      that resolved by the 6-month follow-up evaluation. There were no deaths and no
      patients required tracheostomy placement. The average inpatient stay after
      surgery varied between 72 and 96 hours, without extended intensive care unit
      stays for any patient. CONCLUSIONS: Technologies such as intraoperative CT
      scanning and merged MRI/CT can provide the surgeon with detailed, virtual real
      time information about the extent of complex endoscopic vertebral segment
      resection and brainstem decompression and lessens the prospect of revision or
      secondary procedures in this challenging surgical corridor. Moreover, patients
      experience limited morbidity and can tolerate early oral intake after transnasal
      endoscopic odontoidectomy. Essential to the successful undertaking of these
      endoscopic adventures is 1) an understanding of the endoscopic nasal, skull base,
      and neurovascular anatomy; 2) advanced and extended-length instrumentation
      including navigation; and 3) a team approach between experienced rhinologists and
      spine surgeons comfortable with endoscopic skull base techniques.

PMID- 24580006
TI  - The use of intraoperative navigation for complex upper cervical spine surgery.
AB  - Imaging guidance using intraoperative CT (O-arm surgical imaging system) combined
      with a navigation system has been shown to increase accuracy in the placement of
      spinal instrumentation. The authors describe 4 complex upper cervical spine cases
      in which the O-arm combined with the StealthStation surgical navigation system
      was used to accurately place occipital screws, C-1 screws anteriorly and
      posteriorly, C-2 lateral mass screws, and pedicle screws in C-6. This combination
      was also used to navigate through complex bony anatomy altered by tumor growth
      and bony overgrowth. The 4 cases presented are: 1) a developmental deformity case
      in which the C-1 lateral mass was in the center of the cervical canal causing
      cord compression; 2) a case of odontoid compression of the spinal cord requiring
      an odontoidectomy in a patient with cerebral palsy; 3) a case of an en bloc
      resection of a C2-3 chordoma with instrumentation from the occiput to C-6 and
      placement of C-1 lateral mass screws anteriorly and posteriorly; and 4) a case of
      repeat surgery for a non-union at C1-2 with distortion of the anatomy and
      overgrowth of the bony structure at C-2.

PMID- 24580008
TI  - Thoracolumbar instrumentation with CT-guided navigation (O-arm) in 270
      consecutive patients: accuracy rates and lessons learned.
AB  - OBJECT: Thoracolumbar instrumentation has experienced a dramatic increase in
      utilization over the last 2 decades. However, pedicle screw fixation remains a
      challenging undertaking, with suboptimal placement contributing to postoperative
      pain, neurological deficit, vascular complications, and return to the operating
      suite. Image-guided spinal surgery has substantially improved the accuracy rates
      for these procedures. However, it is not without technical challenges and a
      learning curve for novice operators. The authors present their experience with
      the O-arm intraoperative imaging system and share the lessons they learned over
      nearly 5 years. METHODS: The authors performed a retrospective chart review of
      270 consecutive patients who underwent thoracolumbar pedicle screw fixation
      utilizing the O-arm imaging system in conjunction with StealthStation navigation
      between April 2009 and September 2013 at a single tertiary care center; 266 of
      the patients underwent CT scanning on postoperative Day 1 to evaluate hardware
      placement. The CT scans were interpreted prospectively by 3 neuroradiologists as
      part of standard work flow and retrospectively by 2 neurosurgeons and a senior
      resident. Pedicle screws were evaluated for breaches according to the 3-tier
      classification proposed by Mirza et al. RESULTS: Of 270 patients, 266 (98.5%)
      were included in the final analysis based on the presence of a postoperative CT
      scan. Overall, 1651 pedicle screws were placed in 266 patients and yielded a 5.3%
      breach rate; 213 thoracic and 1438 lumbosacral pedicle screws were inserted with
      6.6% and 5.1% breach rates, respectively. Of the 87 suboptimally placed screws,
      there were 13 Grade 1, 16 Grade 2, and 12 Grade 3 misses as well as 46
      anterolateral or "tip-out" perforations at L-5. Four patients (1.5%) required a
      return to the operating room for pedicle screw revision, 2 of whom experienced
      transient radicular symptoms and 2 remained asymptomatic. Interestingly, the
      pedicle breach rate was higher than anticipated at 13.21% for the 30 patients
      over the initial 6-month period with the O-arm. After certain modifications to
      the authors' technique, the subsequent 30 patients experienced a statistically
      significant decrease in breach rate at 5.6% (p = 0.014). CONCLUSIONS: Image
      guided spinal surgery can be a great option in the operating room and provides
      high pedicle screw accuracy rates. With numerous systems commercially available,
      it is important to develop a systematic approach regardless of the technology in
      question. There is a learning curve for surgeons unfamiliar with image guidance
      that should be recognized and appreciated when transitioning to navigation
      assisted spinal surgery. In fact, the authors' experience with a large patient
      cohort suggests that this learning curve may be more significant than previously
      reported.

PMID- 24580007
TI  - Instrumenting the small thoracic pedicle: the role of intraoperative computed
      tomography image-guided surgery.
AB  - OBJECT: Traditionally, instrumentation of thoracic pedicles has been more
      difficult because of their relatively smaller size. Thoracic pedicles are at risk
      for violation during surgical instrumentation, as is commonly seen in patients
      with scoliosis and in women. The laterally based "in-out-in" approach, which
      technically results in a lateral breach, is sometimes used in small pedicles to
      decrease the comparative risk of a medial breach with neurological involvement.
      In this study the authors evaluated the role of CT image-guided surgery in
      navigating screws in small thoracic pedicles. METHODS: Thoracic (T1-12) pedicle
      screw placements using the O-arm imaging system (Medtronic Inc.) were evaluated
      for accuracy with preoperative and postoperative CT. "Small" pedicles were
      defined as those <= 3 mm in the narrowest diameter orthogonal to the long axis of
      the pedicle on a trajectory entering the vertebral body on preinstrumentation CT.
      A subset of "very small" pedicles (<= 2 mm in the narrowest diameter, 13
      pedicles) was also analyzed. Screw accuracy was categorized as good (< 1 mm of
      pedicle breach in any direction or in-out-in screws), fair (1-3 mm of breach), or
      poor (> 3 mm of breach). RESULTS: Twenty-one consecutive patients (age range 32
      71 years) had large (45 screws) and small (52 screws) thoracic pedicles. The
      median pedicle diameter was 2.5 mm (range 0.9-3 mm) for small and 3.9 mm (3.1-6.7
      mm) for large pedicles. Computed tomography-guided surgical navigation led to
      accurate screw placement in both small (good 100%, fair 0%, poor 0%) and large
      (good 96.6%, fair 0%, poor 3.4%) pedicles. Good screw placement in very small or
      small pedicles occurred with an in-out-in trajectory more often than in large
      pedicles (large 6.8% vs small 36.5%, p < 0.0005; vs very small 69.2%, p <
      0.0001). There were no medial breaches even though 75 of the 97 screws were
      placed in postmenopausal women, traditionally at higher risk for osteoporosis.
      CONCLUSIONS: Computed tomography-guided surgical navigation allows for safe,
      effective, and accurate instrumentation of small (<= 3 mm) to very small (<= 2
      mm) thoracic pedicles.

PMID- 24580009
TI  - Image-guided navigation and video-assisted thoracoscopic spine surgery: the
      second generation.
AB  - OBJECT: Video-assisted thoracoscopic surgery (VATS) has evolved for treatment of
      a variety of spinal disorders. Early incorporation with image-guided surgery
      (IGS) was challenged due to reproducibility and adaptability, limiting the
      procedure's acceptance. In the present study, the authors report their experience
      with second-generation IGS and VATS technologies for anterior thoracic minimally
      invasive spinal (MIS) procedures. METHODS: The surgical procedure is described in
      detail including operating room set-up, patient positioning (a lateral decubitus
      position), placement of the spinal reference frame and portal, radiographic
      localization, registration, surgical instruments, and the image-guided
      thoracoscopic discectomy. RESULTS: Combined IGS and VATS procedures were
      successfully performed and assisted in anatomical localization in 14 patients.
      The mean patient age was 59 years (range 32-73 years). Disc herniation pathology
      represented the most common indication for surgery (n = 8 patients);
      intrathoracic spinal tumors were present in 4 patients and the remaining patients
      had infection and ossification of the posterior longitudinal ligament. All
      patients required chest tube drainage postoperatively, and all but 1 patient had
      drainage discontinued the following day. The only complication was a seroma that
      was presumed to be due to steroid therapy for postoperative weakness. At the
      final follow-up, 11 of the patients were improved neurologically, 2 patients had
      baseline neurological status, and the 1 patient with postoperative weakness was
      able to ambulate, albeit with an assistive device. The evolution of thoracoscopic
      surgical procedures occurring over 20 years is presented, including their
      limitations. The combination of VATS and IGS technologies is discussed including
      their safety and the importance of 3D imaging. In cases of large open thoracotomy
      procedures, surgeries require difficult, extensive, and invasive access through
      the chest cavity; using a MIS procedure can potentially eliminate many of the
      complications and morbidities associated with large open procedures. The authors
      report their experience with thoracic spinal surgeries that involved MIS
      procedures and the new technologies. CONCLUSIONS: The most significant advance in
      IGS procedures has resulted from intraoperative CT scanning and automatic
      registration with the IGS workstation. Image guidance can be used in conjunction
      with VATS techniques for thoracic discectomy, spinal tumors, infection, and
      ossification of the posterior longitudinal ligament. The authors' initial
      experience has revealed this technique to be useful and potentially applicable to
      other MIS procedures.

PMID- 24580010
TI  - Novel placement of cortical bone trajectory screws in previously instrumented
      pedicles for adjacent-segment lumbar disease using CT image-guided navigation.
AB  - OBJECT: Symptomatic adjacent-segment lumbar disease (ASLD) after lumbar fusion
      often requires subsequent surgical intervention. The authors report utilizing
      cortical bone trajectory (CBT) pedicle screw fixation with intraoperative CT (O
      arm) image-guided navigation to stabilize spinal levels in patients with
      symptomatic ASLD. This unique technique results in the placement of 2 screws in
      the same pedicle (1 traditional pedicle trajectory and 1 CBT) and obviates the
      need to remove preexisting instrumentation. METHODS: The records of 5 consecutive
      patients who underwent lumbar spinal fusion with CBT and posterior interbody
      grafting for ASLD were retrospectively reviewed. All patients underwent screw
      trajectory planning with the O-arm in conjunction with the StealthStation
      navigation system. Basic demographics, operative details, and radiographic and
      clinical outcomes were obtained. RESULTS: The average patient age was 69.4 years
      (range 58-82 years). Four of the 5 surgeries were performed with the Minimal
      Access Spinal Technologies (MAST) Midline Lumbar Fusion (MIDLF) system. The
      average operative duration was 218 minutes (range 175-315 minutes). In the entire
      cohort, 5.5-mm cortical screws were placed in previously instrumented pedicles.
      The average hospital stay was 2.8 days (range 2-3 days) and there were no
      surgical complications. All patients had more than 6 months of radiographic and
      clinical follow-up (range 10-15 months). At last follow-up, all patients reported
      improved symptoms from their preoperative state. Radiographic follow-up showed
      Lenke fusion grades of A or B. CONCLUSIONS: The authors present a novel fusion
      technique that uses CBT pedicle screw fixation in a previously instrumented
      pedicle with intraoperative O-arm guided navigation. This method obviates the
      need for hardware removal. This cohort of patients experienced good clinical
      results. Computed tomography navigation was critical for accurate CBT screw
      placement at levels where previous traditional pedicle screws were already placed
      for symptomatic ASLD.

PMID- 24580011
TI  - Introduction: Intraoperative spinal imaging and navigation.

PMID- 24580012
TI  - The future for surgical margins.

PMID- 24580013
TI  - Screening diagnostics to identify triggers in 21 cases of steroid-responsive
      meningitis-arteritis.
AB  - OBJECTIVES: To evaluate whether screening tests used to identify infectious and
      neoplastic triggers for immune-mediated haemolytic anaemia, in particular a
      complete blood count and differential, serum biochemistry profile, urine analysis
      (including culture), abdominal ultrasound and thoracic radiographs, can identify
      triggers for steroid-responsive meningitis-arteritis. METHODS: Retrospective
      descriptive review. RESULTS: Twenty-one steroid-responsive meningitis-arteritis
      cases were identified in which all screening tests had been performed. All cases
      had changes in complete blood count (including neutrophilia, monocytosis,
      lymphocytosis, eosinopenia or anaemia); 19 had changes in biochemistry (including
      hypoalbuminaemia, hyperglobulinaemia, increased alkaline phosphatase activity,
      hyperphosphataemia, increased total calcium concentration, hypercholesterolaemia,
      hyperkalaemia, increased urea concentration and increased alanine
      aminotransferase activity); two cases had an elevated urine protein to creatinine
      ratio but none had positive urine culture results; no cases had abnormalities on
      orthogonal radiographs of the thorax; four cases had abnormalities identified on
      abdominal ultrasound, which following cytological examination suggested
      inflammation in the absence of pathological organisms. CLINICAL SIGNIFICANCE:
      Screening tests used to identify infectious and neoplastic triggers in immune
      mediated haemolytic anaemia did not isolate triggers for steroid-responsive
      meningitis-arteritis in the population of dogs under investigation.

PMID- 24580014
TI  - Comparison of surgical duration of canine ovariectomy and ovariohysterectomy in a
      veterinary teaching hospital.
AB  - OBJECTIVE: To prospectively evaluate ovariectomy and ovariohysterectomy via
      midline coeliotomy when being employed by supervised final year veterinary
      students for the purpose of routine canine neutering. METHODS: One hundred and
      eight female dogs of various breeds, presented to a veterinary teaching hospital
      for neutering, were randomly allocated to one of two surgery groups, ovariectomy
      or ovariohysterectomy. The specified procedure was performed by a supervised
      final year veterinary student. If the duration of surgery exceeded 2 hours or if
      major surgical or anaesthetic complications occurred, the supervising surgeon
      intervened to complete the procedure. RESULTS: Data analysed included age,
      weight, time from first incision to start of closure, duration of closure, total
      surgical time and length of incision. Fifty-four dogs underwent each procedure.
      There was no significant difference between the two surgery groups for any of the
      measured variables. CLINICAL SIGNIFICANCE: Ovariectomy is not associated with
      shorter surgical times or smaller abdominal incisions than ovariohysterectomy
      when employed by inexperienced surgeons. As no major complications novel to
      ovariectomy occurred in this cohort of dogs, this study adds support to the
      existing literature indicating that ovariectomy is an acceptable alternative to
      ovariohysterectomy for canine neutering.

PMID- 24580016
TI  - Intraoperative identification of canine hepatocellular carcinoma with indocyanine
      green fluorescent imaging.
AB  - OBJECTIVES: To evaluate the feasibility of high-sensitivity near-infrared
      fluorescence imaging with indocyanine green for intraoperative identification of
      hepatocellular carcinoma in dogs. METHODS: Twelve hepatic nodules were surgically
      resected from six dogs. In each dog, 0 . 5 mg/kg indocyanine green was
      intravenously injected for 12 to 18 hours preoperatively. The hepatic nodules
      were investigated under laparotomy using a near-infrared fluorescence imaging
      light camera system prior to resection. Resected nodules were histopathologically
      diagnosed and their fluorescence images were evaluated. RESULTS: Of the 12
      hepatic nodules, 6 were diagnosed as hepatocellular carcinoma and 6 as nodular
      hyperplasia. Indocyanine green-fluorescence was observed in four large
      hepatocellular carcinoma nodules and one case of nodular hyperplasia, whereas it
      was absent in the remaining nodules. The sensitivity and positive predictive
      values of indocyanine green fluorescent imaging for hepatocellular carcinoma was
      71 . 4 and 80 . 0%, respectively. Complete resection of the hepatic masses was
      achieved in all dogs. CLINICAL SIGNIFICANCE: Near-infrared fluorescence imaging
      may be feasible for intraoperative mapping of hepatocellular carcinomas in
      hepatic lobes and may help increase the chance of complete resection of
      hepatocellular carcinoma in dogs.

PMID- 24580015
TI  - Investigation of prognostic indicators for human uveal melanoma as biomarkers of
      canine uveal melanoma metastasis.
AB  - OBJECTIVE: To evaluate if 14 genes that discriminate metastasising and non
      metastasising human uveal melanomas can differentiate metastasising and non
      metastasising uveal melanomas in dogs. METHODS: Nineteen archival biopsies of
      eyes with a histopathological classification of primary benign (n = 9) and
      malignant (n = 10) uveal melanoma were selected. Thoracic and/or abdominal
      metastases confirmed metastatic spread of the primary tumour in seven dogs during
      the follow-up period. Gene expression was assayed by Reverse Transcription
      quantitative Polymerase Chain Reaction. Genes displaying statistically
      significant differences in expression between the metastasising and non
      metastasising tumours were identified. RESULTS: Four genes (HTR2B, FXR1, LTA4H
      and CDH1) demonstrated increased expression in the metastasising uveal melanomas.
      CLINICAL SIGNIFICANCE: This preliminary study illustrates the potential utility
      of gene expression markers for predicting canine uveal melanoma metastasis. The
      genes displaying elevated expression in the metastasising tumours are part of a
      12-discriminating gene set used in a routine assay, performed on fine needle
      aspirate biopsies collected without enucleation, for predicting human uveal
      melanoma metastasis. Further work is required to validate the results.

PMID- 24580017
TI  - Global biogeography of Streptomyces antibiotic inhibition, resistance, and
      resource use.
AB  - Although recent molecular techniques have greatly expanded our knowledge of
      microbial biogeography, the functional biogeography of soil microorganisms
      remains poorly understood. In this work, we explore geographic variation in
      Streptomyces phenotypes that are critical to species interactions. Specifically,
      we characterize Streptomyces from different locations from multiple continents
      for antibiotic inhibition, resistance, and resource use phenotypes. Streptomyces
      from different locations varied significantly in antibiotic inhibition,
      resistance, and resource use indicating that communities vary in functional
      potential. Among all isolates, there were substantial differences in antibiotic
      inhibition, resistance, and resource use within and among and within Streptomyces
      species. Moreover, Streptomyces with near-identical 16S rRNA gene sequences from
      different locations sometimes differed significantly in inhibition, resistance,
      and resource use phenotypes, suggesting that these phenotypes may be locally
      adapted. Thus, in addition to a likely role of environmental filtering, variation
      in Streptomyces inhibitory, resistance, and resource use phenotypes among
      locations is likely to be a consequence of local selection mediated by species
      interactions. 

PMID- 24580020
TI  - Language and pragmatic profile in children with ADHD measured by Children's
      Communication Checklist 2nd edition.
AB  - OBJECTIVE: The aim of this study was to explore whether children with attention
      deficit hyperactivity disorder (ADHD) have language and/or pragmatic difficulties
      compared to typically developing children. METHODS: Nineteen children with ADHD
      (age 5-12 years) and nineteen typically developing children (age 5-8 years) were
      evaluated using the Finnish version of Children's Communication Checklist 2nd
      edition (CCC-2). The CCC-2 questionnaire was filled in by their parents. RESULTS:
      According to the CCC-2 questionnaire, differences between the groups were found
      in linguistic abilities, pragmatics skills, and social interaction. CONCLUSION:
      According to the CCC-2 profiles, many children with ADHD may have various kinds
      of communication difficulties, even if they do not have a diagnosed language
      disorder.

PMID- 24580022
TI  - Progress in addiction treatment: from one-size-fits-all to medications and
      treatment matching.
AB  - This paper briefly reviews the development of treatment for substance use
      disorders over the last 100 years from the perspective of the author, who has
      participated in treatment outcome studies since the mid-1970s. It includes some
      personal events that contributed to the author's involvement in addiction
      treatment and research, and describes the gradual evolution of an approach that
      began with a focus on detoxification and psychosocial treatment to one that
      involves blending psychosocial treatments with use of Food and Drug
      Administration (FDA)-approved medications and adding treatments for psychiatric
      and medical disorders when necessary based on patient assessments. It ends with
      comments on the gap between what is known and the degree to which existing
      knowledge is applied, and how the Affordable Care Act holds promise for bridging
      that gap.

PMID- 24580018
TI  - Full-length dystrophin reconstitution with adeno-associated viral vectors.
AB  - Duchenne muscular dystrophy (DMD) is the most common lethal muscle disorder in
      children. It is caused by mutations of the dystrophin gene. Adeno-associated
      virus (AAV)-mediated gene replacement therapy has been actively pursued to treat
      DMD. However, this promising therapeutic modality has been challenged by the
      small packaging capacity of the AAV vector. The size of the full-length
      dystrophin cDNA is >11 kb, while an AAV virus can carry only a 5 kb genome.
      Innovative high-capacity AAV vectors may offer an opportunity to express the full
      length dystrophin coding sequence. Here we describe several sets of tri-AAV
      vectors for full-length human dystrophin delivery. In each set, the full-length
      human dystrophin cDNA was split into three fragments and independently packaged
      into separate recombinant AAV vectors. Each vector was engineered with unique
      recombination signals for directional recombination. Tri-AAV vectors were
      coinjected into the tibialis anterior muscle of dystrophin-deficient mdx4cv mice.
      Thirty-five days after injection, dystrophin expression was examined by
      immunofluorescence staining. Despite low reconstitution efficiency, full-length
      human dystrophin was successfully expressed from the tri-AAV vectors. Our results
      suggest that AAV can be engineered to express an extra-large (up to 15 kb) gene
      that is approximately three times the size of the wild-type AAV genome. Further
      optimization of the trivector strategy may expand the utility of AAV for human
      gene therapy.

PMID- 24580021
TI  - Impact of vocal load on breathiness: perceptual evaluation.
AB  - OBJECTIVES: To evaluate the impact on voice of 2 hours of continuous oral
      reading. METHODS: Fifty normophonic women underwent two sessions of voice loading
      in which the required intensity level varied: 60-65 dB(A) for the first session,
      and 70-75 dB(A) for the second session. Ten expert judges evaluated the
      breathiness of one sentence recorded before and after each loading session. Pairs
      of stimuli were presented randomly to the judges, who were asked to designate the
      breathiest sample. RESULTS: A significant decrease in breathiness was observed
      following both sessions, suggesting an improvement of voice subsequent to
      loading. When comparing the two intensity levels, no difference was found for
      breathiness after vocal loading.

PMID- 24580023
TI  - Stable dosages of clobazam for Lennox-Gastaut syndrome are associated with
      sustained drop-seizure and total-seizure improvements over 3 years.
AB  - OBJECTIVE: To determine long-term safety and efficacy of adjunctive clobazam for
      patients with Lennox-Gastaut syndrome (LGS). METHODS: Eligible patients from two
      randomized controlled trials (Phase II OV-1002 and Phase III OV-1012) were able
      to enroll in open-label extension (OLE) study OV-1004 beginning in December 2005
      and received clobazam until they discontinued (mandatory at 2 years for patients
      outside the United States) or until study completion in March 2012. Patients in
      the United States could have received clobazam for 6 years before it became
      commercially available. Efficacy assessments included changes in rates of drop
      seizures and total seizures, responder rates (>=50%, >=75%, or 100% decreases in
      seizure frequency vs. baseline), sustained efficacy over time, concomitant
      antiepileptic drug (AED) use, and global evaluations. Safety assessments included
      exposure to clobazam, laboratory assessments, physical and neurologic
      examinations, vital sign monitoring, electrocardiography monitoring, and adverse
      event reporting. RESULTS: Of 267 patients who enrolled in the OLE, 188 (70%)
      completed the trial. Two hundred seven patients were from the United States,
      which was the only country in which patients could be treated with clobazam for
      >2 years. Forty-four patients were treated with clobazam for 5 years, and 11 for
      6 years. Because of the low number of Year 6 patients, this group is not reported
      separately. Improvements in baseline seizure rates were very stable over the
      course of the study, with a median 85% decrease in drop seizures at Year 1, 87%
      at Year 2, 92% at Year 3, 97% at Year 4, and a 91% decrease for patients who had
      reached Year 5. Similar results were observed for total seizures (79% decrease at
      both Years 1 and 2, 82% decrease at Year 3, 75% decrease at Year 4, and 85%
      decrease at Year 5). Responder rates were also stable for the duration of the
      trial. Of patients who had achieved a >=50% decrease in median drop-seizure
      frequency from baseline to Month 3, 86% still had that degree of drop-seizure
      reduction at Year 3 (and 14% lost their initial responses), and 47% were drop
      seizure-free. Most patients who had achieved drop-seizure freedom in the original
      controlled trials remained drop-seizure-free in the OLE. Based on parents' and
      physicians' ratings of global evaluations, 80% of patients were "very much
      improved" or "much improved" after 3 years. Of the 43 patients with concomitant
      AED data who were treated for 5 years, 30% increased, 19% decreased, and 51% had
      no change in numbers of AEDs versus their Week 4 regimens. The mean modal
      clobazam dosage was 0.90 mg/kg/day at Year 1 and 0.97 mg/kg/day at Year 5,
      suggesting that study patients did not need significant increases in dosage over
      time. The safety profile was what would be expected for clobazam for LGS patients
      over a 5-year span, and no new safety concerns developed over time. SIGNIFICANCE:
      In this largest and longest-running trial in LGS, adjunctive clobazam sustained
      seizure freedom and substantial seizure improvements at stable dosages through 3
      years of therapy in this difficult- to-treat patient population. A PowerPoint
      slide summarizing this article is available for download in the Supporting
      Information section here.

PMID- 24580024
TI  - Incorporation of Uranium into Hematite during crystallization from ferrihydrite.
AB  - Ferrihydrite was exposed to U(VI)-containing cement leachate (pH 10.5) and aged
      to induce crystallization of hematite. A combination of chemical extractions,
      TEM, and XAS techniques provided the first evidence that adsorbed U(VI) (~3000
      ppm) was incorporated into hematite during ferrihydrite aggregation and the early
      stages of crystallization, with continued uptake occurring during hematite
      ripening. Analysis of EXAFS and XANES data indicated that the U(VI) was
      incorporated into a distorted, octahedrally coordinated site replacing Fe(III).
      Fitting of the EXAFS showed the uranyl bonds lengthened from 1.81 to 1.87 A, in
      contrast to previous studies that have suggested that the uranyl bond is lost
      altogether upon incorporation into hematite. The results of this study both
      provide a new mechanistic understanding of uranium incorporation into hematite
      and define the nature of the bonding environment of uranium within the mineral
      structure. Immobilization of U(VI) by incorporation into hematite has clear and
      important implications for limiting uranium migration in natural and engineered
      environments. 

PMID- 24580025
TI  - Doxorubicin-induced oxidative stress in rats is efficiently counteracted by
      dietary anthocyanin differently enriched strawberry (Fragaria * ananassa Duch.).
AB  - This study investigated the effects of two different strawberry cultivars, Adria
      and Sveva, against doxorubicin (DOX)-induced toxicity in rats. A controlled
      dietary intervention was conducted over 16 weeks with four groups: (i) normal
      diet; (ii) normal diet + DOX injection; (iii) Adria supplementation + DOX
      injection; and (iv) Sveva supplementation + DOX injection. Sveva presented higher
      total antioxidant capacity value and phenol and and vitamin C levels than Adria,
      which in turn presented higher anthocyanin contents. DOX drastically increased
      lymphocyte DNA damage, liver biomarkers of protein and lipid oxidation, and
      mitochondrial ROS content and markedly decreased plasma retinol level, liver
      antioxidant enzymes, and mitochondrial functionality. After 2 months of
      strawberry supplementation, rats presented a significant reduction of DNA damage
      and ROS concentration and a significant improvement of oxidative stress
      biomarkers, antioxidant enzyme activities, and mitochondrial performance. These
      results suggest that strawberry supplementation can counteract DOX toxicity,
      confirming the potential health benefit of strawberry in vivo against oxidative
      stress. 

PMID- 24580027
TI  - Unique excavated rhombic dodecahedral PtCu3 alloy nanocrystals constructed with
      ultrathin nanosheets of high-energy {110} facets.
AB  - Ultrathin crystalline nanosheets give an extremely high surface area of a
      specific crystal facet with unique physical and chemical properties compared with
      normal three-dimensionally polyhedral nanocrystals (NCs). However, the ultrathin
      metal nanosheets tend to curl themselves or assemble with each other sheet by
      sheet, which may reduce the effective surface area and accordingly the catalytic
      activity to a great extent. Here we report a facile wet-chemical route that
      allows the fabrication of novel excavated rhombic dodecahedral (ERD) PtCu3 alloy
      NCs with ultrathin nanosheets of high-energy {110} facets. The surface area was
      measured to be 77 m(2) g(-1) by CO stripping, although the particle size is about
      50 nm. Electrochemical characterizations showed that the ERD PtCu3 NCs exhibit
      excellent electrocatalytic performance and high antipoisoning activity in
      comparison with commercial Pt black and PtCu3 alloy NCs with {111} surfaces. 

PMID- 24580026
TI  - HLA-G +3142 polymorphism as a susceptibility marker in two rheumatoid arthritis
      populations in Brazil.
AB  - In this study, we sought to investigate the genetic influence of two HLA-G 3'
      untranslated region (3'-UTR) polymorphisms - 14 bp (rs66554220) and +3142C>G
      (rs1063320) and their compounding haplotypes in susceptibility to rheumatoid
      arthritis (RA) in a two-region Brazilian study comprising of 539 patients and 489
      controls. All subjects were polymerase chain reaction (PCR) genotyped for the
      referred polymorphisms and logistic regression models controlling for sex, city
      and age were performed. Homozygozity for the +3142G allele was associated with an
      increased risk of RA [odds ratio (OR) = 1.45, 95% confidence interval (CI) =
      1.075-1.959, P(Bonf)  = 0.030], whereas no association was observed for the 14 bp
      polymorphism. Haplotype comparisons between patients and controls showed a
      decreased frequency of the delC haplotype in patients (OR = 0.70, 95% CI = 0.521
      0.946, P(Bonf)  = 0.040), which remained significant in the rheumatoid factor
      (RF)-positive group (OR = 0.66, 95% CI = 0.482-0.900, P(Bonf)  = 0.018), but not
      in the RF-negative group. These results corroborate the hypothesis of an
      involvement of HLA-G in the susceptibility of RA. The +3142G allele is associated
      with haplotype lineages that share high identity and are regarded as low
      producers. The presence of the G allele in homozygosis could be responsible for a
      low HLA-G expression profile that could favor the triggering of RA.

PMID- 24580028
TI  - Two decades on.

PMID- 24580029
TI  - Colin and Heather Waldron: clinicians, teachers, practice builders, travellers,
      professional leaders.

PMID- 24580032
TI  - The impact of intra-clonal heterogeneity on the treatment of multiple myeloma.
AB  - It is clear that cancers comprise a mixture of clones, a feature termed intra
      clonal heterogeneity, that compete for spatial and nutritional resources in a
      fashion that leads to disease progression and therapy resistance. This process of
      competition resembles the schema proposed by Darwin to explain the origin of the
      species, and applying these evolutionary biology concepts to cancer has the
      potential to improve our treatment strategies. Multiple myeloma (MM) has a unique
      set of characteristics that makes it a perfect model in which to study the
      presence of intra-clonal heterogeneity and its impact on therapy. Novel therapies
      have improved the outcome of MM patients, increasing both progression-free and
      overall survival. Current therapy comprises an induction, consolidation and
      maintenance phases and it is important to consider how these components of MM
      therapy are affected by the presence of intra-clonal heterogeneity. In this
      evolutionary context therapy can be considered as a selective pressure
      differentially acting on the myeloma clones and impacting on their chances of
      survival. In this review current knowledge of intra-clonal heterogeneity, as well
      as its impact on the different components of MM treatment is discussed. 

PMID- 24580033
TI  - 'That's just what's expected of you ... so you do it': mothers discussions around
      choice and the MMR vaccination.
AB  - One of the major shifts in the form and experience of contemporary family life
      has been the increasing insertion of the 'expert' voice into the relationship
      between parents and children. This paper focuses on an exploration of mothers'
      engagement with advice around the combined measles, mumps and rubella (MMR)
      vaccine. Much of the previous literature utilises a 'decision-making' framework,
      based on 'risk assessment' whereby mothers' decisions are conceptualised as
      rooted in complex belief systems, and supposes that that by gaining an
      understanding of these systems, beliefs and behaviour can be modified and uptake
      improved. However, less attention has been paid to the ways in which mothers
      negotiate such advice or the ways in which advice is mediated by positionings,
      practices and relationships. Analysis of data from a focus group with five
      mothers identified three themes: (i) Sourcing advice and information, (ii)
      Constructing 'Mother knows best' and (iii) Negotiating agency. Despite the
      trustworthiness of advice and information being questioned, an awareness of
      concerns about the MMR, and health professionals being constructed as remote,
      ultimate conformity to, and compliance with, the 'system' and 'society' were
      described as determining MMR 'decisions'. 

PMID- 24580034
TI  - Characterization of QmnD3/QmnD4 for double bond formation in quartromicin
      biosynthesis.
AB  - In this work, two enzymes responsible for the biogenesis of possible [4 + 2]
      reaction precursors in the quartromicin biosynthetic pathway were characterized:
      acetylation of 1 to yield 2 was catalyzed by QmnD3, and subsequent acetic acid
      elimination of 2 to form double bond product 3 was catalyzed by QmnD4. Site
      directed mutagenesis assay of QmnD3 and QmnD4 was investigated, and a general
      base-catalyzed mechanism for QmnD4 is proposed. 

PMID- 24580035
TI  - Fully printed, highly sensitive multifunctional artificial electronic whisker
      arrays integrated with strain and temperature sensors.
AB  - Mammalian-mimicking functional electrical devices have tremendous potential in
      robotics, wearable and health monitoring systems, and human interfaces. The keys
      to achieve these devices are (1) highly sensitive sensors, (2) economically
      fabricated macroscale devices on flexible substrates, and (3) multifunctions
      beyond mammalian functions. Although highly sensitive artificial electronic
      devices have been reported, none have been fabricated using cost-effective
      macroscale printing methods and demonstrate multifunctionalities of artificial
      electronics. Herein we report fully printed high-sensitivity multifunctional
      artificial electronic whiskers (e-whisker) integrated with strain and temperature
      sensors using printable nanocomposite inks. Importantly, changing the composition
      ratio tunes the sensitivity of strain. Additionally, the printed temperature
      sensor array can be incorporated with the strain sensor array beyond mammalian
      whisker functionalities. The sensitivity for the strain sensor is impressively
      high (~59%/Pa), which is the best sensitivity reported to date (>7* improvement).
      As the proof-of-concept for a truly printable multifunctional artificial e
      whisker array, two- and three-dimensional space and temperature distribution
      mapping are demonstrated. This fully printable flexible sensor array should be
      applicable to a wide range of low-cost macroscale electrical applications. 

PMID- 24580036
TI  - Community fingerprinting in a sequencing world.
AB  - Despite decreasing costs, generating large-scale, well-replicated and
      multivariate microbial ecology investigations with sequencing remains an
      expensive and time-consuming option. As a result, many microbial ecology
      investigations continue to suffer from a lack of appropriate replication. We
      evaluated two fingerprinting approaches - terminal restriction fragment length
      polymorphism (T-RFLP) and automated ribosomal intergenic spacer analysis (ARISA)
      against 454 pyrosequencing, by applying them to 225 polar soil samples from East
      Antarctica and the high Arctic. By incorporating local and global spatial scales
      into the dataset, our aim was to determine whether various approaches differed in
      their ability and hence utility, to identify ecological patterns. Through the
      reduction in the 454 sequencing data to the most dominant OTUs, we revealed that
      a surprisingly small proportion of abundant OTUs (< 0.25%) was driving the
      biological patterns observed. Overall, ARISA and T-RFLP had a similar capacity as
      sequencing to separate samples according to distance at a local scale, and to
      correlate environmental variables with microbial community structure.
      Pyrosequencing had a greater resolution at the global scale but all methods were
      capable of significantly differentiating the polar sites. We conclude
      fingerprinting remains a legitimate approach to generating large datasets as well
      as a cost-effective rapid method to identify samples for elucidating taxonomic
      information or diversity estimates with sequencing methods.

PMID- 24580037
TI  - Increased macrophage density of cardiac allograft biopsies is associated with
      antibody-mediated rejection and alloantibodies to HLA antigens.
AB  - BACKGROUND: Antibody-mediated rejection (AMR) is characterized histologically by
      intracapillary macrophages. Macrophage density may be an alternative method of
      determining inflammatory changes in AMR. METHODS: We identified 118 heart
      transplant patients with serologic testing for HLA alloantibodies. Macrophage
      density was graded as 1+ (<45/mm(2)), 2+ (46-90/mm(2)), and 3+ (>90/mm(2)).
      Maximal macrophage density and complement staining over multiple biopsies were
      correlated with peak panel reactive antibodies (PRA), donor-specific antibodies
      (DSA), and the clinical diagnosis of AMR. RESULTS: The presence of PRA correlated
      with macrophage score (p = 0.001). Macrophage density correlated with any DSA (p
      < 0.0001), class I DSA (p < 0.0001), class II DSA (p < 0.0001), and class II DQ
      (p < 0.0001). Nine patients had clinical AMR. Among patients with AMR, 89% had a
      biopsy over the period of AMR with >=3+ macrophage density (89% sensitivity);
      among patients without AMR, 93% of patients had no biopsy at any time with >=3+
      macrophage density (specificity). There was perfect concordance between the
      scores of C4d positivity and macrophage density in 61% and only partial
      concordance in 20%, with complete discordance in 19% in biopsies taken during
      clinical episodes of AMR. CONCLUSIONS: Macrophage density in allograft
      endomyocardial biopsies is frequently elevated during clinical episodes of AMR
      and correlates well with alloantibodies.

PMID- 24580039
TI  - The imaging and the fractal metrology of chimeric liposomal Drug Delivery nano
      Systems: the role of macromolecular architecture of polymeric guest.
AB  - The major advance of mixed liposomes (the so-called chimeric systems) is to
      control the size, structure, and morphology of these nanoassemblies, and
      therefore, system colloidal properties, with the aid of a large variety of
      parameters, such as chemical architecture and composition. The goal of this study
      is to investigate the alterations of the physicochemical and morphological
      characteristics of chimeric dipalmitoylphosphatidylcholine (DPPC) liposomes,
      caused by the incorporation of block and gradient copolymers (different
      macromolecular architecture) with different chemical compositions (different
      amounts of hydrophobic component). Light scattering techniques were utilized in
      order to characterize physicochemically and to delineate the fractal morphology
      of chimeric liposomes. In this study, we also investigated the structural
      differences between the prepared chimeric liposomes as are visualized by scanning
      electron microscopy (SEM). It could be concluded that all the chimeric liposomes
      have regular structure, as SEM images revealed, while their fractal
      dimensionality was found to be dependent on the macromolecular architecture of
      the polymeric guest.

PMID- 24580040
TI  - Primary biliary cirrhosis in adults.
AB  - Primary biliary cirrhosis (PBC) is a chronic, autoimmune, cholestatic liver
      disease. It is characterized by slow destruction of small intrahepatic bile
      ducts, impaired biliary secretion and stasis of toxic endogenous bile acids
      within the liver with progression to liver fibrosis and cirrhosis. It has an
      increasing prevalence worldwide. It occurs more commonly in women than men at a
      ratio of 10:1. In most cases, diagnosis relies on a positive antimitochondrial
      antibody in the context of chronic cholestasis, without the need for a liver
      biopsy. Ursodeoxycholic acid improves survival even in patients with advanced
      liver disease. Certain findings such as fatigue, anti-nuclear antibodies, anti
      centromere antibodies and the GP210 antinuclear antibody predict a poor outcome.
      Up to 40% of patients do not respond satisfactorily to ursodeoxycholic acid
      therapy and should be considered for adjunctive therapies. Several adjunctive and
      newer therapies are being tested and some appear promising. We provide a review
      of PBC with a focus on advances in therapies that may impact the management of
      PBC in the near future. 

PMID- 24580041
TI  - The effects of sleeve gastectomy on gastro-esophageal reflux and gastro
      esophageal motility.
AB  - Sleeve gastrectomy is an increasingly performed bariatric procedure associated
      with low morbidity and good short to medium term effects on weight loss and
      comorbid conditions. Studies assessing the prevalence of post-operative gastro
      esophageal reflux disease (GERD), show sleeve gastrectomy may provoke de novo
      GERD symptoms or worsening of pre-existing GERD. Pathophysiological mechanisms of
      GERD after sleeve gastrectomy include a hypotensive lower esophageal sphincter,
      increased gastro-esophageal pressure gradient and intra-thoracic migration of the
      remnant stomach. A reduction in the compliance of the gastric remnant may provoke
      an increase in transient lower esophageal sphincter relaxations. Time-resolved
      MRI suggests relative gastric stasis in the proximal remnant and increased
      emptying from the antrum. A lack of standardisation of technique, along with
      heterogeneity of studies assessing GERD may explain the wide variability in
      reported results. Simultaneous and careful repair of an associated hiatus hernia
      may result in a reduction in the prevalence of post-operative GERD. 

PMID- 24580042
TI  - Using patient-reported outcomes to improve the management of co-infection with
      HIV and HCV: the ANRS CO13 HEPAVIH cohort.
AB  - The management of co-infection with HIV and hepatitis C virus (HCV) is
      complicated by viral and drug-drug interactions, treatment-related side effects,
      and the poor response to therapy of certain HCV genotypes. Current or past drug
      use may also have a negative impact. HEPAVIH (ANRS CO13) is an ongoing French
      cohort study of co-infected individuals which combines medical and socio
      behavioral follow-up. This cohort study aims at analyzing the course of HCV
      infection and access to HCV treatment in HIV-HCV co-infected patients, using both
      clinical and patient-reported outcomes. This article documents the main lessons
      learned to date from the HEPAVIH data and published literature, while describing
      research prospects and needs requiring further investigation in the field of
      patient-reported outcomes. 

PMID- 24580043
TI  - Irritable bowel syndrome: recent developments in diagnosis, pathophysiology, and
      treatment.
AB  - The diagnosis of irritable bowel syndrome (IBS) remains a diagnosis of exclusion,
      whereby an extensive investigation is performed to exclude other organic diseases
      that may explain the symptoms of patients. Attempts to have a positive diagnosis
      based on symptom assessments failed to achieve widely use in clinical practice.
      Abnormalities in the gastrointestinal endocrine cells in IBS patients have been
      reported recently, providing evidence that IBS is an organic disorder, and
      opening the door to the use of these abnormalities as markers for a positive
      diagnosis of IBS. New and promising drugs for the treatment of IBS with
      constipation as the predominant symptom are currently on the market, and the
      treatment results have been satisfactory thus far. 

PMID- 24580044
TI  - Metformin in the treatment of non-alcoholic fatty liver disease: safety, efficacy
      and mechanism.
AB  - Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease
      etiology worldwide. It encompasses a spectrum ranging from simple steatosis to
      non-alcoholic steatohepatitis. Although the physiopathology of NAFLD is partly
      known. Insulin-resistance plays a central role in the development and progression
      of NAFLD. Several studies have indicated that metformin, as an insulin
      sensitizer, effectively improves NAFLD and its related metabolic status.
      Metformin was effective in reducing enzyme levels in the short period, but very
      limited and controversial information are available on liver histology. Larger
      randomized controlled trials of sufficient duration using clearly defined
      histological endpoints are needed to fully assess the efficacy of this drug in
      modifying the natural history of NAFLD. 

PMID- 24580045
TI  - Can specific calcium channel blockade be the basis for a drug-based treatment of
      acute pancreatitis?

PMID- 24580046
TI  - Managing hepatitis B to prevent liver cancer: recent advances.
AB  - Chronic hepatitis B (CHB) infection is a major cause of human mortality
      worldwide. The majority of people with CHB are infected early in life, and 20-40%
      of men and 15% of women with chronic infection will develop hepatocellular
      carcinoma (HCC). Antiviral therapy is recommended for patients with CHB who have
      cirrhosis or active disease with the aims of reducing disease progression to
      cirrhosis, liver failure and liver cancer, thereby preventing death. Evidence
      that treatment with interferon or with early nucleos(t)ide analogue therapy
      reduces HCC has been somewhat conflicting, however evidence is emerging to
      support a significant role in HCC prevention of the more effective antivirals,
      entecavir and tenofovir. Older patients, those with cirrhosis, and those
      undergoing curative treatments for HCC derive the greatest medium-term benefit in
      terms of HCC reduction, but HCC can still occur and long-term surveillance is
      recommended. 

PMID- 24580047
TI  - Inflammatory bowel disease in women of reproductive age.
AB  - Management of inflammatory bowel disease in women of reproductive age requires
      special attention. Even though fertility in women without previous pelvis surgery
      is similar to the general population, active disease at conception and during
      pregnancy can lead to unfavorable pregnancy and fetal outcomes. In general, most
      medications needed to treat inflammatory bowel disease are low risk during
      pregnancy and breastfeeding. Achieving and maintaining disease remission, patient
      education, and a multidisciplinary team approach is the key to a successful
      pregnancy. 

PMID- 24580048
TI  - Molecular dynamics simulations of uranyl and uranyl carbonate adsorption at
      aluminosilicate surfaces.
AB  - Adsorption at mineral surfaces is a critical factor controlling the mobility of
      uranium(VI) in aqueous environments. Therefore, molecular dynamics (MD)
      simulations were performed to investigate uranyl(VI) adsorption onto two neutral
      aluminosilicate surfaces, namely, the orthoclase (001) surface and the octahedral
      aluminum sheet of the kaolinite (001) surface. Although uranyl preferentially
      adsorbs as a bidentate inner-sphere complex on both surfaces, the free energy of
      adsorption on the orthoclase surface (-15 kcal mol(-1)) is significantly more
      favorable than that at the kaolinite surface (-3 kcal mol(-1)), which is
      attributed to differences in surface functional groups and the ability of the
      orthoclase surface to release a surface potassium ion upon uranyl adsorption. The
      structures of the adsorbed complexes compare favorably with X-ray absorption
      spectroscopy results. Simulations of the adsorption of uranyl complexes with up
      to three carbonate ligands revealed that uranyl complexes coordinated to up to
      two carbonate ions are stable on the orthoclase surface whereas uranyl carbonate
      surface complexes are unfavored at the kaolinite surface. Combining the MD
      derived equilibrium adsorption constants for orthoclase with aqueous equilibrium
      constants for uranyl carbonate species indicates the presence of adsorbed uranium
      complexes with one or two carbonates under alkaline conditions, in support of
      current uranium(VI) surface complexation models. 

PMID- 24580049
TI  - Thromboelastometry as a supplementary tool for evaluation of hemostasis in severe
      sepsis and septic shock.
AB  - BACKGROUND: Sepsis leads to disruption of hemostasis, making early evaluation of
      coagulation essential. The aim of this study was to provide a detailed
      investigation of coagulation and the use of blood products in patients with
      severe sepsis or septic shock, admitted to a multidisciplinary intensive care
      unit. METHODS: Thirty-six patients with severe sepsis or septic shock were
      included in this prospective observational study. Blood samples and information
      on transfusion of blood products were obtained for up to 3 consecutive days, and
      day 7 if the patient was still in the intensive care unit. Thromboelastometry
      (ROTEM((r))), analyses of thrombin generation, and conventional coagulation tests
      were performed. RESULTS: ROTEM((r)) revealed an overall normo-coagulable state
      among patients with severe sepsis or septic shock. Conventional coagulation
      analyses showed divergent results with hypercoagulable trends in terms of reduced
      antithrombin and acute phase response with increased fibrinogen and fibrin d
      dimer, and on the other hand, coagulation disturbances with a decreased
      prothrombin time and prolonged activated partial thromboplastin time. This
      hypocoagulabe state was supported by a delayed and reduced thrombin generation.
      Twelve patients experienced 21 independent transfusion episodes with fresh frozen
      plasma. Of these, only five (22%) transfusions were performed because of active
      bleeding. CONCLUSION: ROTEM((r)) demonstrated an overall normo-coagulation,
      whereas the conventional coagulation tests and thrombin generation analyses
      mainly reflected hypocoagulation. Given the dynamic and global features of
      ROTEM((r)), this analysis may be a relevant supplementary tool for the assessment
      of hemostasis in patients with severe sepsis or septic shock.

PMID- 24580050
TI  - Adenovirus-based vaccines for fighting infectious diseases and cancer: progress
      in the field.
AB  - The field of adenovirology is undergoing rapid change in response to increasing
      appreciation of the potential advantages of adenoviruses as the basis for new
      vaccines and as vectors for gene and cancer therapy. Substantial knowledge and
      understanding of adenoviruses at a molecular level has made their manipulation
      for use as vaccines and therapeutics relatively straightforward in comparison
      with other viral vectors. In this review we summarize the structure and life
      cycle of the adenovirus and focus on the use of adenovirus-based vectors in
      vaccines against infectious diseases and cancers. Strategies to overcome the
      problem of preexisting antiadenovirus immunity, which can hamper the
      immunogenicity of adenovirus-based vaccines, are discussed. When armed with tumor
      associated antigens, replication-deficient and oncolytic adenoviruses can
      efficiently activate an antitumor immune response. We present concepts on how to
      use adenoviruses as therapeutic cancer vaccines and consider some of the
      strategies used to further improve antitumor immune responses. Studies that
      explore the prospect of adenoviruses as vaccines against infectious diseases and
      cancer are underway, and here we give an overview of the latest developments.

PMID- 24580051
TI  - Clinical, neuropsychological, and metabolic characteristics of transient
      epileptic amnesia syndrome.
AB  - OBJECTIVE: Transient epileptic amnesia (TEA) is a recently individualized
      syndrome occurring in adult patients that includes epileptic seizures with
      amnestic features and interictal memory disturbances. METHODS: We investigated
      the clinical, neuropsychological, and 18F-FDG positron emission tomography (18F
      FDG-PET) features of 30 consecutive cases of TEA in our center. RESULTS: The mean
      age of onset of amnestic seizures was 59 years. Pure acute amnesia was the only
      epileptic manifestation in 17% of cases. Interictal electroencephalography (EEG)
      abnormalities were present in 57% on awake recording and in most patients in whom
      sleep EEG was performed (96%). Nine of 30 patients showed anterograde memory
      deficit and six of 30 exhibited mild executive functioning impairment. On the
      autobiographical memory interview (AMI), patients showed a significant deficit
      for the recent period of the episodic subscale. Outcome under treatment was
      favorable in the majority of cases. A significant improvement was noted on
      recollection of autobiographical memory. 18F-FDG-PET (22 cases) showed positive
      correlations between left mesial temporal metabolism levels and anterograde and
      retrograde memory scores. SIGNIFICANCE: TEA is an emerging epileptic syndrome
      that likely remains misidentified and misdiagnosed. Neurometabolic data support a
      dysfunction of a hippocampal-neocortical network sustaining episodic memory.

PMID- 24580052
TI  - President's Annual State of the Academy Report.

PMID- 24580053
TI  - The Walking Corsi Test (WalCT): a normative study of topographical working memory
      in a sample of 4- to 11-year-olds.
AB  - We report normative data on topographical working memory collected through the
      Walking Corsi Test (WalCT; Piccardi et al., 2008 ) for developing a standard
      administration procedure to be used in clinical and educational practice. A total
      of 268 typically developing Italian children aged 4-11 years performed both WalCT
      and Corsi Block-Tapping Test (CBT; Corsi, 1972 ) a well-known visuo-spatial
      memory test. WalCT has already been validated in adults, demonstrating
      sensitivity in detecting topographical memory deficits even in individuals who
      have no other memory impairments. Our results showed that age, but not sex,
      affected performances. Both girls and boys had a larger span on the CBT than the
      WalCT. The youngest group did not differ in performing WalCT and CBT, but from
      5.6 years of age children performed better on CBT than WalCT, suggesting that
      memory in reaching space develops before topographical memory. Only after 5 years
      of age do children learn to process specifically topographical stimuli,
      suggesting that this happens when their environmental knowledge becomes
      operational and they increase environmental independence. We also discuss the
      importance to introduce WalCT in the clinical assessment. 

PMID- 24580055
TI  - Suicide by non-pharmaceutical poisons in San Diego County.
AB  - BACKGROUND: In 2010, 6,599 poisoning suicides were reported in the United States
      (US). While medications remain the primary substances involved in completed
      poisoning suicides, successful fatal poisonings with non-pharmaceutical
      substances occur with some regularity. The goal of this study was to identify
      successful suicides caused by non-pharmaceutical self-poisoning in a large US
      county over the last 12 years. METHODS: A large US-county medical-examiner's
      database was queried for all suicides in which exposure to non-pharmaceuticals
      was listed as the cause of death from 2000 to 2012. Substances were categorized
      by specific toxin when available and by product type when unavailable. Decedent
      age, sex, and circumstances surrounding each case were also reviewed. RESULTS:
      Ages ranged from 18 to 95 (median 48) years. There were 159 (77%) males and 48
      females. A total of 11 poisons were utilized. DISCUSSION: Worldwide, intentional
      CO inhalation is a common method for committing suicide and intentional CO
      inhalation was the most common method of non-pharmaceutical self-poisoning
      suicide in our data. Other relatively common poisons including ethylene glycol
      and cyanide were employed in a relatively constant manner over time as well.
      Surprisingly, there have been an increasing number of helium-inhalation deaths in
      recent years. CONCLUSION: Inhaled toxins are the most popular (81%) in non
      pharmaceutical suicides, likely due to their rapidity of death. Although much
      less frequently, individuals successfully employ a broad spectrum of other toxins
      to commit suicide.

PMID- 24580054
TI  - Microarray discovery of new OGT substrates: the medulloblastoma oncogene OTX2 is
      O-GlcNAcylated.
AB  - O-GlcNAc transferase (OGT) is a serine/threonine glycosyltransferase that is
      essential for development and continues to be critically important throughout
      life. Understanding OGT's complex biology requires identifying its substrates.
      Here we demonstrate the utility of a microarray approach for discovering novel
      OGT substrates. We also report a rapid method to validate OGT substrates that
      combines in vitro transcription-translation with O-GlcNAc mass tagging. Among the
      validated new OGT targets is Orthodenticle homeobox 2 (OTX2), a transcription
      factor critical for brain development, which is primarily expressed only during
      early embryogenesis and in medulloblastomas, where it functions as an oncogene.
      We show that endogenous OTX2 from a medulloblastoma cell line is O-GlcNAcylated
      at several sites. Our results demonstrate that protein microarray technology,
      combined with the target validation strategy we report, is useful for identifying
      biologically important OGT substrates, including substrates not present in most
      tissue types or cell lines. 

PMID- 24580056
TI  - Three months of methoxetamine administration is associated with significant
      bladder and renal toxicity in mice.
AB  - CONTEXT.: Methoxetamine is a ketamine analogue that has recently emerged as a
      novel psychoactive substance. Chronic ketamine use is associated with significant
      bladder and renal toxicity. Methoxetamine has been marketed as "bladder
      friendly", but there is no data to be able to substantiate this claim. OBJECTIVE:
      To characterise the patterns of bladder and renal toxicity associated with 3
      months of methoxetamine administration in an animal model. MATERIALS AND METHODS:
      Two-month-old Institute of Cancer Research mice were administered 30 mg/kg
      methoxetamine intraperitoneally (n = 5) or saline (n = 3 control) for 3 months.
      The animals were then sacrificed and histological examination, immuno
      cytochemistry using polyclonal anti-CD4 antibodies and sirius-red staining for
      collagen were performed. RESULTS: The kidneys of methoxetamine-treated animals
      showed inflammatory cell infiltration, tubular cell necrosis and glomerular
      damage (1.9 +/- 0.3% shrunken glomeruli in control, 9.8 +/- 0.8% in methoxetamine
      treated mice (p < 0.0001); 2.9 +/- 0.3% tubular cell degeneration in control,
      20.4 +/- 1.1% in methoxetamine-treated mice (p < 0.0001)). There was a greater
      density of mononuclear cells in the bladder lamina propria and submucosa in
      methoxetamine-treated mice (43.0 +/- 2.1 per 250 * 250 MUm) than controls (7.1 +/
      1.2 per 250 * 250 MUm), p < 0.001. CD4-positive staining was seen in the bladder
      submucosa and lamina propria of all methoxetamine-treated mice and muscle-layer
      of two methoxetamine-treated mice; these changes were not seen in the control
      mice. There was an increase in sirius-red collagen in the bladder sub-mucosa and
      muscle-layer in the methoxetamine-treated mice compared with control mice.
      DISCUSSION: This study has shown that 3 months of daily 30 mg/kg intra-peritoneal
      methoxetamine results in significant bladder and renal toxicity in mice. Changes
      in the bladder included inflammatory changes with subsequent fibrosis and changes
      in the kidney were seen at both a tubular and glomerular level. These changes are
      similar to those seen in comparable animal models of chronic ketamine
      administration. Further work is required to determine the time course of the
      onset of these effects and whether the effects are reversible with methoxetamine
      cessation.

PMID- 24580057
TI  - Misdiagnosis and long-term outcome of 13 patients with acute thallium poisoning
      in China.
AB  - PURPOSE: To analyze clinical feature and evaluate long-term outcome of patients
      with thallium poisoning. MATERIALS AND METHODS: An observational series of cases
      with acute thallium poisoning was analyzed retrospectively in West China Hospital
      of Sichuan University between 2000 and 2010. The clinical data including symptom,
      determination of thallium level, treatment, neurophysiological examination, and
      neuropsychological evaluation were analyzed. The patients were followed up until
      December 2012. RESULTS: Seven men and six women were enrolled in the study. The
      median patient age was 37 years (range: 15-53 years). The median duration of
      hospitalization was 44 days (range: 7-72). All the patients were misdiagnosed
      initially. One patient died in the hospital. The other 12 patients were followed
      for a median of 7 years (range: 1-12 years) after discharge from hospital. One
      patient died from leukemia in the first year of follow-up. Long-term outcome
      results showed peripheral neuropathy improved substantially. However, many
      patients have mild or moderate sequelae in sensory nerve fibers of distal lower
      extremity. A sural nerve biopsy in one patient revealed shrunken axons, distorted
      myelin sheath, and myelinated fibers loss. During follow-up period, problem of
      intelligence (4/12 patients, 33%), memory impairment (4/12, 33%), anxiety (6/12,
      50%), and depression (5/12, 42%) were demonstrated. CONCLUSIONS: Neurological
      symptoms may lead to misdiagnosis of thallium poisoning. Mild or moderate
      neurological sequelae may last for a long time after thallium poisoning.

PMID- 24580058
TI  - Rapid diagnosis of Naja atra snakebites.
AB  - BACKGROUND: The clinical diagnosis of snakebites is critical and necessary in
      many parts of the world, especially in Southeastern Asia, where venomous
      snakebites are a burden on public health. It is difficult to define or recognize
      the species of venomous snake because of the overlapping clinical manifestations
      of envenomations. A quick and reliable method for identifying the snake species
      is necessary. We designed and tested a strip of lateral flow system for the
      diagnosis of cobra snake bites in Taiwan. METHODS: We developed a kit based on an
      immunochromatographic method for rapid detection of cobra (Naja atra) venom in
      human serum. The test and control lines composed of 1 mg/ml polyclonal duck
      antivenom and 0.5 mg/ml goat anti-rabbit immunoglobulin antibody solutions,
      respectively, were coated on nitrocellulose strips. Colloidal gold was conjugated
      with rabbit polyclonal anti-cobra venom antibodies. From July 2007 to December
      2012, we used the kit to test serum from snakebite patients and to examine the
      agreement between our rapid test and the currently used sandwich enzyme-linked
      immunosorbent assay (ELISA). RESULTS: Our kit was able to detect cobra venom in
      serum samples in 20 minutes with a detection limit of 5 ng/ml. An absence of
      cross-reactivity with other non-cobra venoms from Taiwan was noted in vitro. A
      total of 88 snakebite patients (34 cobra and 54 other non-cobra) were tested. The
      sensitivity of the strips based on the ELISA results was 83.3% and the
      specificity was 100%. There was a strong agreement between the results of the
      ELISA and immunochromatographic strips (kappa = 0.868). DISCUSSION AND
      CONCLUSIONS: This data indicates that an immunochromatographic strip might be
      suitable for cobra venom detection and could be used as a quick diagnostic tool
      in cases of N. atra snakebite.

PMID- 24580059
TI  - Patterns of presentation and clinical toxicity after reported use of alpha
      methyltryptamine in the United Kingdom. A report from the UK National Poisons
      Information Service.
AB  - OBJECTIVE: To characterise the patterns of presentation, clinical effects and
      possible harms of acute toxicity following recreational use of alpha
      methyltryptamine (AMT) in the United Kingdom, as reported by health professionals
      to the National Poisons Information Service (NPIS) and to compare clinical
      effects with those reported after mephedrone use. METHODS: NPIS telephone
      enquiries and TOXBASE user sessions, the NPIS online information database,
      related to AMT were reviewed from March 2009 to September 2013. Telephone enquiry
      data were compared with those for mephedrone, the recreational substance most
      frequently reported to the NPIS, collected over the same period. RESULTS: There
      were 63 telephone enquiries regarding AMT during the period of study, with no
      telephone enquiries in 2009 or 2010, 19 in 2011, 35 in 2012 and 9 in 2013 (up to
      September). Most patients were male (68%) with a median age of 20 years. The
      route of exposure was ingestion in 55, insufflation in 4 and unknown in 4 cases.
      Excluding those reporting co-exposures, clinical effects recorded more frequently
      in AMT (n = 55) compared with those of mephedrone (n = 488) users including acute
      mental health disturbances (66% vs. 32%; Odds Ratio [OR], 4.00; 95% Confidence
      Intervals [CI], 2.22-7.19), stimulant effects (66% vs. 40%; OR, 2.82; 95% CI 1.57
      5.06) and seizures (14% vs. 2%; OR, 9.35; 95% CI 3.26-24.18). CONCLUSIONS:
      Although still infrequent, toxicity following reported exposure to AMT has been
      encountered in the United Kingdom since January 2011. Stimulant features, acute
      mental health disturbances and seizures are more frequently reported than in
      those presenting following reported use of mephedrone.

PMID- 24580060
TI  - The association between U.S. Poison Center assistance and length of stay and
      hospital charges.
AB  - CONTEXT: Poison centers (PCs) play an important role in poison prevention and
      treatment. Studies show that PCs reduce system-wide cost by reducing the number
      of unnecessary visits to emergency departments and by providing improved patient
      management. However, there remains a debate regarding the impact of PCs on
      patient outcomes at the hospital level. OBJECTIVE: To evaluate the impact of PC
      involvement on length of hospitalization and total hospital charges. MATERIALS
      AND METHODS: We conducted a retrospective analysis of inpatient cases treated in
      Illinois hospitals in 2010. We linked the Illinois Poison Center database with an
      Illinois hospital billing dataset and controlled for important patient-level and
      facility-level covariates. RESULTS: In the multivariable model, length of
      hospitalization among PC-assisted patients was 0.58 days shorter than that of
      patients without PC assistance (p < 0.001). Hospital charges for PC-assisted
      patients in the lower quintiles were significantly higher than patients without
      PC assistance (+$953; p < 0.001), but were substantially lower in the most costly
      quintile of patients (-$4852; p < 0.001). Balancing the higher charges for
      treating patients with PC assistance in the lower quintiles with the savings in
      the highest quintile, among inpatients there is a potential cumulative decrease
      of $2,078 in hospital charges per 10 patients. DISCUSSION: Among the inpatient
      cases, PC assistance was associated with lower total charges only among the most
      expensive to treat. However, this outlier group is very important when discussing
      medical costs. It has been repeatedly shown that the majority of treatment costs
      are attributable to a small fraction of patients as seen in this study.

PMID- 24580061
TI  - Toxicity and clinical outcomes of paliperidone exposures reported to U.S. Poison
      Centers.
AB  - CONTEXT: Paliperidone is an atypical antipsychotic that was approved in the U.S.
      in 2006, and is also available in Canada, Australia, New Zealand, Europe, and
      Asia. Information regarding paliperidone overdoses is limited to case reports.
      Serious toxicity has yet to be reported. OBJECTIVE: To evaluate the toxicity of
      paliperidone exposures using a national poison center database. METHODS: A
      retrospective, observational case series of single-substance paliperidone cases
      reported to the National Poison Data System from 2007 to 2012 was conducted.
      Cases were evaluated for demographics, reason for exposure, clinical effects,
      treatments, disposition, and coded medical outcomes. For cases with major effects
      the text fields in poison center charts were evaluated to verify accuracy of
      coded outcome. The relationship between dose and severity of medical outcome was
      analyzed for acute exposure cases. RESULTS: There were 801 paliperidone cases
      that met inclusion criteria that included 592 persons of 13 years or greater, 67
      children of 6-12 years, 140 children of less than 6 years, and 2 unknown ages.
      Most common reasons for exposure included: suicide attempt (39.6%), unintentional
      general (21.1%), therapeutic error (15.7%), and adverse drug reaction (11.9%).
      The most commonly observed clinical effects were drowsiness/lethargy (28.7%),
      tachycardia (23.3%), and dystonia (14.2%). Most patients were managed in the
      emergency department (40.3%) or were admitted to a health care facility (HCF)
      (42.7%). In 564 cases treated in a HCF, treatments included activated charcoal
      (25.7%), antihistamines (21.1%), and benzodiazepines (9.4%). Medical outcomes
      were no effect (35.0%), minor (30.8%), moderate (33.7%), and major effect (0.5%).
      There were no deaths. Of 491 acute exposures, dose was coded for 74.3% of
      exposures. There was a significant difference in the reported median dose between
      those with no effect (6 mg) and either minor effect (12 mg; p = 0.047) or
      moderate effect cases (12 mg; p = 0.020) in 91 children less than 6 years.
      CONCLUSIONS: The majority of patients experienced no or minor toxicity and were
      not admitted for medical care. Although a higher dose was associated with a more
      serious outcome in children less than 6 years, the data do not provide clear-cut
      triage guidelines.

PMID- 24580062
TI  - Serious adverse effects from single-use detergent sacs: report from a U.S.
      statewide poison control system.
AB  - BACKGROUND: In recent years, serious adverse effects to children from exposure to
      single-use detergents sacs (SUDS) have been recognized. While most exposures
      result in minor symptoms, there have been serious outcomes. This study aims to
      classify which types of serious outcomes follow SUDS exposures, and to assess, if
      possible, differences in toxicity between various SUDS products. METHODS: An
      observational case series with data collected retrospectively was performed for
      cases of SUDS exposures reported to a statewide poison system's records database
      from 1 January 2012 to 31 March 2013. Cases were identified and analyzed for
      clinical details and trends. A statewide database was queried for cases involving
      the American Association of Poison Control Centers (AAPCC) product-specific codes
      for SUDS products using following search terms: laundry pods, the AAPCC product
      specific codes for Tide Pods, Purex Ultrapacks, ALL Mighty Pacs, and a unique
      agent code (AAPCC ID: 6903138; Generic: 077900) created by AAPCC to track SUDS
      exposures. RESULTS: A total of 804 cases of exposures to SUDS were identified,
      the majority of which were exploratory ingestions in young children with a median
      age of 2 years. Serious adverse effects resulted from 65 (9%) exposures and 27
      (3%) exposures resulted in admission to hospital. Binary logistic regression
      demonstrated that the presence of central nervous system (CNS) or respiratory
      system effects were associated with more severe outcomes, with a model accuracy
      of 96.4%. There were significant differences in morbidity among the three most
      common brand-name products: when compared with Tide Pods, odds ratios (OR) and
      95% confidence intervals (CI) for severe outcome and admission rate were
      significantly greater following Purex Ultrapack exposures (severity OR 5.1 [CI:
      2.13-12.23]; admission OR 10.36 [CI: 3.23-33.22]) and ALL Mighty Pac exposures
      (severity OR 11.22 [CI: 4.78-28.36]; admission OR 15.20 [CI: 5.01-46.12]).
      CONCLUSIONS: Serious complications from exposure to SUDS occur in a small number
      of exposures for unclear reasons. Respiratory and CNS effects are associated with
      more severe outcomes. Some brand-name products are associated with a relatively
      higher risk of severe adverse effects and rates of admission.

PMID- 24580063
TI  - A retrospective review of isolated gliptin-exposure cases reported to a state
      poison control system.
AB  - BACKGROUND: The dipeptidyl peptidase-4 (DPP-4) inhibitors sitagliptin,
      saxagliptin, and linagliptin are approved by the US Food and Drug Administration
      in the treatment of type-2 diabetes. Given the limited published information
      regarding human overdoses to these medications, our goal was to characterize such
      exposures. METHODS: A state poison system database was retrospectively reviewed
      for all single-agent exposures to sitagliptin, saxagliptin, and linagliptin from
      2006 to 2012. Case notes were reviewed and an observational case series was
      constructed from the data collected including age, weight, gender, circumstances
      surrounding exposure, symptoms, and outcome. Patients with co-ingestants,
      confirmed non-exposure, unknown outcomes, or other coding errors were excluded.
      RESULTS: A total of 197 cases were identified: 135 cases were excluded (123 cases
      were excluded due to co-ingestants and 12 cases were lost to follow-up); 62 were
      included for review. No patients experienced hypoglycemia. One of 19 exposed
      pediatric (0-9 years of age) patients experienced symptoms and was safely managed
      at home after one episode of emesis. No symptom was experienced following
      unintentional ingestion by three adolescent (10-18 years of age) patients. Forty
      single-agent adult exposures to gliptins were included. Thirty-seven involved non
      self-harm exposures resulting from double or triple doses; all were safely
      managed at home without reported symptoms. The majority of these ingestions
      involved sitagliptin. Three self-harm-adult exposures to gliptins were included
      for review. All the three were evaluated in a healthcare facility. One patient
      experienced abdominal discomfort after ingesting 700 mg of sitagliptin and was
      ultimately discharged from the emergency department. The other two patients
      experienced no reported symptoms. CONCLUSION: The majority of gliptin-exposed
      adult and pediatric/adolescent patients were safely managed at home and when
      evaluated in a healthcare facility, did not require hospitalization. Intentional
      self-harm-adult gliptin exposures were managed in a healthcare facility but
      rarely resulted in hospitalization or serious morbidity at doses up to 18 times
      the adult therapeutic dose. Additional studies are necessary to determine precise
      triage guidelines for the management of gliptin overdose.

PMID- 24580064
TI  - Chronic hematuria and abdominal pain.
AB  - An 18-year-old Asian woman with a history of substance abuse presented to the
      Emergency Department with right-sided abdominal pain and hematuria of several
      months duration. Physical examination revealed right upper quadrant and
      suprapubic tenderness. Liver function tests were normal. Urinalysis showed: large
      blood, 30-50 red blood cells/high-powered field, and no bacteria. She underwent a
      CT of the abdomen and pelvis following oral and intravenous contrast.

PMID- 24580066
TI  - The binding modes of cationic porphyrin-anthraquinone hybrids to DNA duplexes: in
      silico study.
AB  - Cationic porphyrin-anthraquinone hybrids bearing peripheral substituents, either
      pyridine, imidazole, or pyrazole rings have been investigated for their binding
      mode to DNA duplexes. The four kinds of DNA duplexes were used, which represent
      intercalation and groove binding modes. AutoDock 4.2 was used to dock nine hybrid
      compounds to four DNA duplexes, while monitoring of conformational changes of
      four best hybrid-DNA complexes during 2 ns was performed by Amber9 molecular
      dynamics package. The binding energy calculation of best four complexes was then
      carried out using MMPBSA method. The hybrid compounds interacted to DNA duplexes
      through intercalation and groove binding modes. The minor groove binding of DNA
      was energetically preferred by cationic porphyrin hybrids due to favorable
      electrostatic and van der Waals interactions. Both electrostatic and van der
      Waals contributions were able to distinguish the binding mode of porphyrin hybrid
      to DNA duplexes. 

PMID- 24580067
TI  - Screening, brief intervention, and referral to treatment (SBIRT) as an integral
      part of nursing practice.
AB  - ABSTRACT. Substance use screening, brief intervention, and referral to treatment
      (SBIRT) should be an integral part of the scope of nursing practice. This
      commentary is an appeal for nurses to advance their knowledge and competencies
      related to SBIRT. The question of how to move SBIRT into the mainstream of
      nursing practice was posed to several leaders of federal agencies, health care
      and nursing organizations, nurse educators, and nurse leaders. The authors
      provide recommendations for moving this set of clinical strategies (i.e., SBIRT)
      into day-to-day nursing practice. 

PMID- 24580068
TI  - Early parenting, represented family relationships, and externalizing behavior
      problems in children born preterm.
AB  - Through assessment of 173 preterm infants and their mothers at hospital discharge
      and at 9, 16, 24, 36, and 72 months, the study examined early parenting,
      attachment security, effortful control, and children's representations of family
      relationships in relation to subsequent externalizing behavior problems. Less
      intrusive early parenting predicted more secure attachment, better effortful
      control skills, and fewer early behavior problems, although it did not directly
      relate to the structural or content characteristics of children's represented
      family relationships. Children with higher effortful control scores at 24 months
      had more coherent family representations at 36 months. Moreover, children who
      exhibited less avoidance in their family representations at 36 months had fewer
      mother-reported externalizing behavior problems at 72 months. The study suggests
      that early parenting quality and avoidance in children's represented
      relationships are important for the development of externalizing behavior
      problems in children born preterm.

PMID- 24580069
TI  - Angiogenic factors and uterine Doppler velocimetry in early- and late-onset
      preeclampsia.
AB  - OBJECTIVE: To assess correlations between maternal serum levels of pro- and anti
      angiogenic factors with uterine perfusion in women with early- compared with late
      onset preeclampsia, and in healthy pregnant women. DESIGN: Case-control study.
      SETTING: Antenatal care clinic located within a hospital (Sao Bernardo do Campo,
      Brazil). POPULATION: We enrolled 54 preeclamptic and 54 healthy control women who
      were coming for routine ultrasound at 28-36 weeks' gestation. METHODS: All
      participants had uterine artery and umbilical Doppler studies and a blood sample
      to assess maternal serum levels of soluble fms-like tyrosine kinase-1, soluble
      endoglin, adiponectin and plasminogen activator inhibitor-1. All angiogenic
      factors were measured using enzyme-linked immunosorbent assay. MAIN OUTCOME
      MEASURES: Levels of pro- and anti-angiogenic factors in maternal serum, and
      uterine artery Doppler findings. RESULTS: Concentrations of soluble fms-like
      tyrosine kinase-1 and soluble endoglin were significantly higher in preeclamptic
      than control women (p < 0.0001 and p < 0.0001, respectively), especially in those
      with early-onset (<34 weeks) preeclampsia. These two anti-angiogenic mediators
      were significantly correlated with increased uterine artery Doppler in the
      preeclamptic women. Plasminogen activator inhibitor-1 levels were significantly
      higher in preeclampsia (p = 0.03) but unrelated to uterine artery resistance.
      Adiponectin levels were similar in cases and controls, independent of body mass
      index and unrelated to uterine artery resistance. CONCLUSION: Preeclamptic
      patients have increased soluble fms-like tyrosine kinase-1 and soluble endoglin
      serum levels and this increase is directly correlated with uterine artery
      resistance, especially in those with early-onset preeclampsia.

PMID- 24580071
TI  - Opportunities and progress.
AB  - In this review, I cover my professional experiences in food science and
      technology and related areas of applied and industrial microbiology over the span
      of my career. It emphasizes opportunities and technological problems that I
      encountered together with my progress in follow-up development of products and
      processes. 

PMID- 24580070
TI  - Proliferation of murine c-kit(pos) cardiac stem cells stimulated with IGF-1 is
      associated with Akt-1 mediated phosphorylation and nuclear export of FoxO3a and
      its effect on downstream cell cycle regulators.
AB  - Insulin-like growth factor-1 (IGF-1) is known to promote proliferation in many
      cell types including c-kit(pos) cardiac stem cells (CSCs). Downstream signaling
      pathways of IGF-1 induced CSC proliferation have not been investigated. An
      important downstream target of IGF-1/Akt-1 signaling is FoxO3a, a key negative
      regulator of cell-cycle progression. We studied the effect of IGF-1 on
      proliferation of c-kit(pos) murine CSCs and found that IGF-1-mediated cell
      proliferation is associated with FoxO3a phosphorylation and inactivation of its
      transcriptional activity. PI3 inhibitors LY294002 and Wortmannin abolished the
      effect of IGF-1 on FoxO3a phosphorylation indicating that FoxO3a phosphorylation
      is mediated by PI3/Akt-1 pathway. In cells with FoxO3a translocation to the
      cytoplasm, there is decreased expression of cell-cycle inhibitors such as
      p27(kip1) and p57(kip2) and increased expression of CyclinD1. Our study provides
      evidence that IGF-1 induced CSC proliferation could be the result of FoxO3a
      inactivation and its downstream effect on cell-cycle regulators.

PMID- 24580072
TI  - Body weight regulation and obesity: dietary strategies to improve the metabolic
      profile.
AB  - This review discusses dietary strategies that may improve the metabolic profile
      and body weight regulation in obesity. Recent evidence demonstrated that long
      term health effects seem to be more beneficial for low-glycemic index (GI) diets
      compared to high-protein diets. Still, these results need to be confirmed by
      other prospective cohort studies and long-term clinical trials, and the
      discrepancy between these study designs needs to be explored in more detail.
      Furthermore, the current literature is mixed with regard to the efficacy of
      increased meal frequency (or snacking) regimens in causing metabolic alterations,
      particularly in relation to body weight control. In conclusion, a growing body of
      evidence suggests that dietary strategies with the aim to reduce postprandial
      insulin response and increase fat oxidation, and that tend to restore metabolic
      flexibility, have a place in the prevention and treatment of obesity and
      associated metabolic disorders. 

PMID- 24580073
TI  - Production of aroma compounds in lactic fermentations.
AB  - This review describes recent scientific research on the production of aroma
      compounds by lactic acid bacteria (LAB) in fermented food products. We discuss
      the various precursor molecules for the formation of aroma compounds in
      connection with the metabolic pathways involved. The roles of nonmetabolic
      properties such as cell lysis are also described in relation to aroma formation.
      Finally, we provide an overview of the literature on methods to steer and control
      aroma formation by LAB in mixed culture fermentations. We demonstrate that the
      technological progress made recently in high-throughput analysis methods has been
      driving the development of new approaches to understand, control, and steer aroma
      formation in (dairy) fermentation processes. This currently entails proposing new
      rules for designing stable, high-performance mixed cultures constituting a
      selection of strains, which in concert and on the basis of their individual
      predicted gene contents deliver the required functionalities. 

PMID- 24580077
TI  - Lots of clots and rods.

PMID- 24580079
TI  - Reactions of size-selected copper cluster cations and anions with nitric oxide:
      enhancement of adsorption in coadsorption with oxygen.
AB  - Reactions of size-selected Cu(n)(+/-) and Cu(n)O(m)(+/-) (n = 3-19, m <= 9)
      clusters with NO were investigated in the near-thermal energy region under single
      collision conditions using a tandem-type mass spectrometer with two ion-guided
      cells. Oxygen atoms preadsorbed on the cluster can significantly enhance the NO
      adsorption probability and cause additional reactions. NO adsorption is observed
      particularly for anionic copper cluster dioxides, Cu(n)O2(-) (n >= 8), followed
      by the release of a Cu atom from Cu(n)O2(-) (n = 8, 10, and 12), which suggests
      that NO adsorbs strongly, i.e., dissociatively on these clusters. Density
      functional theory calculations support that dissociative adsorption of NO occurs
      in the reaction of Cu8O2(-) under the present experimental conditions. On the
      other hand, NO oxidation proceeds in reactions of oxygen-rich cluster cations
      such as Cu4O3(+), Cu6O5(+), Cu9O7(+), and Cu11O8(+).

PMID- 24580074
TI  - Three-component coupling approach for the synthesis of diverse heterocycles
      utilizing reactive nitrilium trapping.
AB  - The formation of an unexpected heterocyclic scaffold, a benzoxazole, in a three
      component reaction between a ketone, isocyanide, and 2-aminophenol was
      encountered. This reaction involved a benzo[b][1,4]oxazine intermediate resulting
      from intramolecular attack of the aminophenol hydroxyl group on the nitrilium
      ion. Unlike previous literature examples, the trapped nitrilium
      benzo[b][1,4]oxazine could readily be subjected to ring opening with bis
      nucleophiles. The reaction scope includes simple linear as well as complex cyclic
      ketones and substituted 2-aminophenols. A representative benzoxazole product
      could be further diversified to yield drug-like compounds. 

PMID- 24580080
TI  - Legionella detection by culture and qPCR: Comparing apples and oranges.
AB  - Legionella spp. are the causative agent of Legionnaire's disease and an
      opportunistic pathogen of significant public health concern. Identification and
      quantification from environmental sources is crucial for identifying outbreak
      origins and providing sufficient information for risk assessment and disease
      prevention. Currently there are a range of methods for Legionella spp.
      quantification from environmental sources, but the two most widely used and
      accepted are culture and real-time polymerase chain reaction (qPCR). This paper
      provides a review of these two methods and outlines their advantages and
      limitations. Studies from the last 10 years which have concurrently used culture
      and qPCR to quantify Legionella spp. from environmental sources have been
      compiled. 26/28 studies detected Legionella at a higher rate using qPCR compared
      to culture, whilst only one study detected equivalent levels of Legionella spp.
      using both qPCR and culture. Aggregating the environmental samples from all 28
      studies, 2856/3967 (72%) tested positive for the presence of Legionella spp.
      using qPCR and 1331/3967 (34%) using culture. The lack of correlation between
      methods highlights the need to develop an acceptable standardized method for
      quantification that is sufficient for risk assessment and management of this
      human pathogen. 

PMID- 24580081
TI  - Conjugated estrogens combined with bazedoxifene: the first approved tissue
      selective estrogen complex therapy.
AB  - Menopausal therapy with a tissue selective estrogen complex combines estrogens
      with a selective estrogen receptor modulator, with the goal of blending the
      desirable effects of estrogens on menopausal symptoms and bone with the tissue
      selective properties of a selective estrogen receptor modulator. The first tissue
      selective estrogen complex to receive regulatory approval is a combination of
      conjugated estrogens (CE) with bazedoxifene (BZA). Clinical trials with CE/BZA in
      postmenopausal women have shown improvement in vasomotor symptoms, vulvo-vaginal
      atrophy, and bone mineral density, without stimulation of the endometrium or
      breast tissue, with a generally favorable safety and tolerability profile. CE/BZA
      represents a new approach to the management of menopausal symptoms in women with
      a uterus. 

PMID- 24580082
TI  - Riociguat for pulmonary hypertension.
AB  - Pulmonary hypertension, an elevation of the mean pulmonary artery pressure >=25
      mmHg, ultimately leads to premature death due to right ventricular dysfunction.
      Ten treatments from three classes of drugs are licensed for the management of
      pulmonary arterial hypertension. These treatments have improved exercise capacity
      but median survival is still poor. Additionally there are no licensed therapies
      for the other groups of pulmonary hypertension. Riociguat is a novel drug that
      stimulates soluble guanylate cyclase independently of nitric oxide and in synergy
      with nitric oxide. This review summarises the available evidence for riociguat in
      the treatment across all groups of pulmonary hypertension with a focus on
      pulmonary arterial hypertension and chronic thromboembolic pulmonary
      hypertension. 

PMID- 24580083
TI  - What are our pharmacotherapeutic options for MERS-CoV?
AB  - Since the initial description of Middle East Respiratory Syndrome-coronavirus
      (MERS-CoV), the disease has been associated with a high case-fatality rate. There
      is a lack of proven effective medications for therapy of MERS-CoV. The current
      knowledge of therapeutic options for MERS-CoV is based on the experience from
      SARS-CoV and from in vitro studies. In this article we review the different
      therapeutics available for MERS-CoV from SARS experience, in vitro and animal
      studies of this emerging disease. 

PMID- 24580084
TI  - Current and investigational pharmacotherapeutic approaches for modulating retinal
      angiogenesis.
AB  - Retinal vascular development is a carefully orchestrated developmental process
      during which retinal and choroidal vasculature form to provide a dual vascular
      supply to the neurosensory retina and retinal pigment epithelium. The most common
      causes of vision loss in children and adults involve at least in part
      perturbation of the normal vascular physiology or development. Vascular
      endothelial growth factor has emerged as a key molecular regulator of retinal
      vascular development as well as retinal and choroidal neovascularization, which
      underlie the pathophysiology of many retinal diseases. Over the past decade, the
      advent of injectable pharmacotherapeutic agents into the vitreous cavity of the
      eye has revolutionized our management of neovascular age-related macular
      degeneration and other retinal diseases and has, for the first time, offered an
      opportunity to improve vision rather than just slow the progression of disease
      processes. The transient duration of these agents, however, requires chronic
      treatment with repeated intraocular injections and significant treatment burden
      for patients and the healthcare system. Novel treatments modulating retinal
      angiogenesis offer the promise of improved efficacy, decreased treatment burden
      and improved cost-effectiveness. 

PMID- 24580085
TI  - Adrenaline increases blood-brain-barrier permeability after haemorrhagic cardiac
      arrest in immature pigs.
AB  - BACKGROUND: Adrenaline (ADR) and vasopressin (VAS) are used as vasopressors
      during cardiopulmonary resuscitation. Data regarding their effects on blood-brain
      barrier (BBB) integrity and neuronal damage are lacking. We hypothesised that VAS
      given during cardiopulmonary resuscitation (CPR) after haemorrhagic circulatory
      arrest will preserve BBB integrity better than ADR. METHODS: Twenty-one
      anaesthetised sexually immature male piglets (with a weight of 24.3 +/- 1.3 kg)
      were bled 35% via femoral artery to a mean arterial blood pressure of 25 mmHg in
      the period of 15 min. Afterwards, the piglets were subjected to 8 min of
      untreated ventricular fibrillation followed by 15 min of open-chest CPR. At 9 min
      of circulatory arrest, piglets received amiodarone 1.0 mg/kg and hypertonic
      hyperoncotic solution 4 ml/kg infusions for 20 min. At the same time, VAS 0.4
      U/kg was given intravenously to the VAS group (n = 9) while the ADR group
      received ADR 20 MUg/kg (n = 12). Internal defibrillation was attempted from 11
      min of cardiac arrest to achieve restoration of spontaneous circulation. The
      experiment was terminated 3 h after resuscitation. RESULTS: The intracranial
      pressure (ICP) in the post-resuscitation phase was significantly greater in ADR
      group than in VAS group. VAS group piglets exhibited a significantly smaller BBB
      disruption compared with ADR group. Cerebral pressure reactivity index showed
      that cerebral blood flow autoregulation was also better preserved in VAS group.
      CONCLUSIONS: Resuscitation with ADR as compared with VAS after haemorrhagic
      circulatory arrest increased the ICP and impaired cerebrovascular autoregulation
      more profoundly, as well as exerted an increased BBB disruption though no
      significant difference in neuronal injury was observed.

PMID- 24580086
TI  - Gastric emptying rate, glycemic and appetite response to a liquid meal in lean
      and overweight males.
AB  - The effect of body weight status on appetite, glycemic response and gastric
      emptying rate was investigated using a liquid meal. Lean and overweight males
      rated their subjective appetite with blood samples collected for measurement of
      glucose, biomarkers of appetite and gastric emptying rate for 3 h following
      consumption of the isocaloric test meal. Overweight participants had a higher
      rating on postprandial hunger (p < 0.001), preoccupation with food (p < 0.001)
      and desire to eat (p < 0.001), with fullness being lower (p = 0.001).
      Postprandial plasma concentration of cholecystokinin-33 was lower (p = 0.007) and
      total ghrelin was higher (p = 0.012) in overweight participants. A delayed
      gastric emptying rate was observed in lean participants. There was no difference
      in postprandial glycemic response (p = 0.189). These results suggest the
      postprandial appetite pattern was different between lean and overweight males
      when consuming an isocaloric meal. This may have implications for overweight
      individuals who attempt to lose weight through restricting food intake.

PMID- 24580087
TI  - Vertical distributions of radionuclides ((239+240)Pu, (240)Pu/(239)Pu, and
      (137)Cs) in sediment cores of Lake Bosten in Northwestern China.
AB  - Artificial radionuclides ((137)Cs, (239+240)Pu, (241)Pu, (241)Am) deposited in
      lacustrine sediments have been used for dating as well as radionuclide source
      identification. In the present work, we investigated the vertical distributions
      of (239+240)Pu and (137)Cs activities, (240)Pu/(239)Pu atom ratios, and
      (239+240)Pu/(137)Cs activity ratios in sediment cores collected from Lake Bosten,
      which is the lake closest to the Lop Nor Chinese Nuclear Weapon Test site in
      northwestern China. Uniformly high concentrations of (239+240)Pu and (137)Cs were
      found in the upper layers deposited since 1964 in the sediment cores, and these
      were controlled by the resuspension of soil containing radionuclides from the
      nearby land surface. As the Chinese nuclear tests varied remarkably in yield, the
      mixing of the tropospheric deposition from these tests and the stratospheric
      deposition of global fallout has led to a (240)Pu/(239)Pu atom ratio that is
      similar to that of global fallout and to a (239+240)Pu/(137)Cs activity ratio
      that is slightly higher than that of global fallout. However, a low
      (240)Pu/(239)Pu atom ratio of 0.080 and high (239+240)Pu/(137)Cs activity ratio
      of 0.087, significantly different from the global fallout values, were observed
      in one sediment core (07BS10-2), indicating the inhomogenous tropospheric
      deposition from the Chinese nuclear tests in Lake Bosten during 1967-1973. These
      results are important to understand the influence of the CNTs on the radionuclide
      contamination in Lake Bosten. 

PMID- 24580089
TI  - A formula for collaborative writing.

PMID- 24580090
TI  - The Great American Cookie Experiment updated for the millennial learner.

PMID- 24580088
TI  - Changes in waist circumference and incidence of chronic kidney disease.
AB  - BACKGROUND: Many studies have evaluated the association of anthropometric indices
      with chronic kidney disease (CKD), but the association of waist circumference(WC)
      changes with CKD incidence is less clear. We evaluated the effect of WC changes
      on CKD incidence in participants of the Tehran Lipid and Glucose Study (TLGS).
      STUDY DESIGN: The risk of CKD incidence was evaluated in three serial phases with
      interval censoring. A group of 8,183 (46.5% men) participants, mean age 47.4
      years, free of previous CKD, were followed. Waist changes were divided into four
      groups: (i)decrease in WC; (ii) reference group; (iii)mild to moderate increase
      in WC and (iv)severe increase in WC. Glomerular filtration rate(GFR) was
      estimated using the MDRD equation. RESULTS: In 8,183 participants, mean GFR was
      higher in men (77.1 vs. 74.4 mL/min/1.73 m2, P<0.001). During the 9 years of
      follow-up, 1477 new cases of CKD occurred(1026 in women). WC changes were not
      associated with the development of CKD in women. In men, decrease in WC was not
      related to lower risk of CKD (HR: 0.90, 95% CI 0.6-1.4), whereas a mild to
      moderate increase in WC was associated with a 70% (HR: 1.7, 95% CI 1.3-2.2)
      higher risk of CKD even after adjusting for covariates (HR: 1.6, 95% CI 1.2-2.2).
      Severe increase in WC was associated with a fourfold risk of CKD in comparison
      with reference group (HR: 3.7, 95% CI 2.7-5.1). CONCLUSION: Changes in WC are not
      independent risk factors for CKD development in women, whereas waist gain can
      adversely influence the development of CKD in men.

PMID- 24580091
TI  - Effect of different monomer-based composites and acid etching pre-treatment of
      enamel on the microleakage using self-etch adhesives systems.
AB  - OBJECTIVE: To evaluate quantitatively the marginal microleakage of restorations
      carried out with self-etching adhesives with or without prior phosphoric enamel
      acid etching of silorane or methacrylate resin-based composite restorations
      subjected to thermal cycling. MATERIALS AND METHODS: Forty cavities were prepared
      at the proximal surface of bovine incisors and randomly divided according to the
      etching of the enamel and restorative system used. The groups were restored with
      methacrylate [Adper SE Plus adhesive (3M ESPE) + Filtek Z250 (3M ESPE)] or
      silorane [Filtek LS adhesive (3M ESPE) + Filtek LS composite (3M ESPE)]
      restorative systems, light-cured using a LED unit (Bluephase 16i, Vivadent).
      After restorative procedure and thermocycling (1000 cycles), the specimens were
      immersed in methylene blue for 2 h. The specimens were triturated and the powder
      was used for analysis in an absorbance spectrophotometer. Data were statistically
      analyzed by 2-way ANOVA (alpha = 0.05). RESULTS: No statistical difference
      between the restorative materials tested with or without previous acid etching of
      enamel in Class II marginal microleakage was observed (p > 0.05). CONCLUSIONS:
      The use of acid etching prior to self-etching adhesives did not interfere on the
      microleakage of methacrylate- or silorane-based restorations.

PMID- 24580092
TI  - Chondrogenic potential of stem cells from human exfoliated deciduous teeth in
      vitro and in vivo.
AB  - OBJECTIVE: The aim of this study was to investigate the chondrogenic potential of
      stem cells from human exfoliated teeth (SHED). MATERIALS AND METHODS: SHED
      cultures were isolated from human exfoliated deciduous teeth. Colony-forming
      capacity, odonto/osteogenic and adipogenic potential were measured. SHED were
      cultured for 2 weeks in chondrogenic differentiation medium containing
      dexamethasone, insulin, ascorbate phosphate, TGF-beta3 and bFGF. Toluidine blue
      staining and safranin O staining were used for chondrogenesis analysis. The
      related markers, type II collagen and aggrecan, were also investigated using
      immunohistochemistry. SHED were seeded onto the beta-TCP scaffolds and
      transplanted into the subcutaneous space on the back of nude mice. The
      transplants were recovered at 2, 4 and 8 weeks post-transplantation for analysis.
      RESULTS: SHED showed colony-forming capacity, odonto/osteogenic and adipogenic
      differentiation capacity. Chondrogenic differentiation was confirmed by toluidine
      blue staining, safranin O staining, type II collagen and aggrecan immunostaining.
      After in vivo transplantation, SHED recombined with beta-TCP scaffolds were able
      to generate new cartilage-like tissues. CONCLUSIONS: The findings demonstrate the
      chondrogenic differentiation capacity of SHED both in vitro and in vivo models,
      suggesting the potential of SHED in cartilage tissue engineering.

PMID- 24580093
TI  - Iridium-catalyzed intermolecular amidation of sp3 C-H bonds: late-stage
      functionalization of an unactivated methyl group.
AB  - Reported herein is the iridium-catalyzed direct amidation of unactivated sp(3) C
      H bonds. With sulfonyl and acyl azides as the amino source, the amidation occurs
      efficiently under mild conditions over a wide range of unactivated methyl groups
      with high functional group tolerance. This procedure can be successfully applied
      for the direct introduction of an amino group into complex compounds and thus can
      serve as a powerful synthetic tool for late-stage C-H functionalization. 

PMID- 24580094
TI  - Solution-processed, barrier-confined, and 1D nanostructure supported quasi
      quantum well with large photoluminescence enhancement.
AB  - Planar substrate supported semiconductor quantum well (QW) structures are not
      amenable to manipulation in miniature devices, while free-standing QW
      nanostructures, e.g., ultrathin nanosheets and nanoribbons, suffer from
      mechanical and environmental instability. Therefore, it is tempting to fashion
      high-quality QW structures on anisotropic and mechanically robust supporting
      nanostructures such as nanowires and nanoplates. Herein, we report a solution
      quasi-heteroepitaxial route for growing a barrier-confined quasi-QW structure
      (ZnSe/CdSe/ZnSe) on the supporting arms of ZnO nanotetrapods, which have a 1D
      nanowire structure, through the combination of ion exchange and successive
      deposition assembly. This resulted in highly crystalline and highly oriented
      quasi-QWs along the whole axial direction of the arms of the nanotetrapod because
      a transition buffer layer (Zn(x)Cd(1-x)Se) was formed and in turn reduced the
      lattice mismatch and surface defects. Significantly, such a barrier-confined QW
      emits excitonic light ~17 times stronger than the heterojunction (HJ)-type
      structure (ZnSe/CdSe, HJ) at the single-particle level. Time-resolved
      photoluminescence from ensemble QWs exhibits a lifetime of 10 ns, contrasting
      sharply with ~300 ps for the control HJ sample. Single-particle PL and Raman
      spectra suggest that the barrier layer of QW has completely removed the surface
      trap states on the HJ and restored or upgraded the photoelectric properties of
      the semiconductor layer. Therefore, this deliberate heteroepitaxial growth
      protocol on the supporting nanotetrapod has realized a several micrometer long QW
      structure with high mechanical robustness and high photoelectric quality. We
      envision that such QWs integrated on 1D nanostructures will largely improve the
      performance of solar cells and bioprobes, among others.

PMID- 24580095
TI  - The effect of cloudy apple juice on hepatic and mammary gland phase I and II
      enzymes induced by DMBA in female Sprague-Dawley rats.
AB  - Apples abundant in phenolic compounds show a variety of biological activities
      that may contribute to health beneficial effects against cardiovascular diseases,
      diabetes, obesity and cancer. We investigated the effect of cloudy apple juice
      (CAJ) on the hepatic and mammary gland carcinogen metabolizing enzymes, DNA
      damage and liver injury, altered by 7,12-dimethylbenz[a]anthracene (DMBA).
      Sprague-Dawley female rats were gavaged with CAJ (10 ml/kg b.w.) for 28
      consecutive days. DMBA was administered i.p. on the 27th and the 28th days. In
      the liver, feeding with CAJ decreased the activities of CYP1A1 and 1A2 and
      increased phase II enzymes. The activities of all enzymes tested were enhanced in
      the animals treated with DMBA alone and in combination with CAJ. The most
      significant changes in the level of the hepatic enzymes tested were observed for
      GST alpha and NQO1. In mammary gland CAJ induced an increase in the level of GST
      mu and GST pi, while DMBA and CAJ combined administration elevated GST pi only.
      This may be beneficial as GST pi is involved in the DMBA detoxification.
      Additionally, pretreatment with CAJ reduced the level of most of the blood
      biochemical liver and kidney markers elevated as a result of DMBA treatment.
      These findings indicate that CAJ may interfere with enzyme system involved in
      carcinogen metabolism. However, this effect seems to be dependent on tissue and
      carcinogen and is moderately effective in the case of DMBA. Moreover, CAJ can
      also provide some protection against the liver and kidney damage.

PMID- 24580096
TI  - Examination of fabrication conditions of acrylate-based hydrogel formulations for
      doxorubicin release and efficacy test for hepatocellular carcinoma cell.
AB  - The objective of the present study was to develop 2-hydroxypropyl methacrylate-co
      polyethylene methacrylate [p(HPMA-co-PEG-MEMA)] hydrogels that are able to
      efficiently entrap doxorubicin for the application of loco-regional control of
      the cancer disease. Systemic chemotherapy provides low clinical benefit while
      localized chemotherapy might provide a therapeutic advantage. In this study,
      effects of hydrogel properties such as PEG chains length, cross-linking density,
      biocompatibility, drug loading efficiency, and drug release kinetics were
      evaluated in vitro for targeted and controlled drug delivery. In addition, the
      characterization of the hydrogel formulations was conducted with swelling
      experiments, permeability tests, Fourier transform infrared, SEM, and contact
      angle studies. In these drug-hydrogel systems, doxorubicin contains amine group
      that can be expected a strong Lewis acid-base interaction between drug and polar
      groups of PEG chains, thus the drug was released in a timely fashion with an
      electrostatic interaction mechanism. It was observed that doxorubicin release
      from the hydrogel formulations decreased when the density of cross-linking, and
      drug/polymer ratio were increased while an increase in the PEG chains length of
      the macro-monomer (i.e. PEG-MEMA) in the hydrogel system was associated with an
      increase in water content and doxorubicin release. The biocompatibility of the
      hydrogel formulations has been investigated using two measures: cytotoxicity test
      (using lactate dehydrogenase assay) and major serum proteins adsorption studies.
      Antitumor activity of the released doxorubicin was assessed using a human SNU398
      human hepatocellular carcinoma cell line. It was observed that doxorubicin
      released from all of our hydrogel formulations which remained biologically active
      and had the capability to kill the tested cancer cells. 

PMID- 24580098
TI  - A physician-centered approach to addiction identification and treatment misses
      the opportunity for interdisciplinary solutions.

PMID- 24580097
TI  - Pregnancy rates of beef cattle are not affected by Campylobacter fetus subsp.
      venerealis real-time PCR-positive breeding sires in New Zealand.
AB  - AIMS: Campylobacter fetus subspecies venerealis (C. fetus venerealis) is the
      causal agent of bovine genital campylobacteriosis, a venereal disease that is
      asymptomatic in bulls but responsible for reproductive wastage in female cattle.
      In New Zealand, a commercial real-time PCR assay was introduced in 2007 to
      identify the DNA of this pathogen in preputial scrapings; however, concerns were
      raised about the specificity of the test following anecdotal reports of a high
      number of test-positive bulls with no apparent relationship to reproductive
      performance. The objective of this study, therefore, was to examine the
      association between real-time PCR assay results from beef breeding bulls and
      pregnancy rates in beef herds using these bulls. METHODS: Veterinarians from four
      veterinary practices selected beef cattle herds with relatively high and low
      pregnancy rates between December 2008 and February 2009. Preputial scrapings were
      collected from bulls used for mating in those herds. Samples were tested using
      the real-time PCR assay under consideration. Bivariable and multivariable
      analyses were used to assess the relationship between pregnancy rates in each mob
      (15-month-old heifers, 27-month-old heifers and mixed-age cows) and the
      percentage of real-time PCR-positive bulls in each mob. RESULTS: Sixty-four
      (28.8%) of 222 bulls tested positive, 130 (58.6%) tested negative, and 28 (12.6%)
      returned an inconclusive result to the real-time PCR assay. The percentage of
      bulls testing real-time PCR-positive in these mobs was not associated with
      pregnancy rates (p=0.757) after controlling for mob, average body condition score
      of cows, cow to bull ratio, length of the mating period, and farm. CONCLUSION:
      Real-time PCR assay results were not associated with pregnancy rates, suggesting
      that the specificity of the real-time PCR assay was too low to be used to
      reliably detect C. fetus venerealis. This study adds to a growing body of
      evidence indicating that C. fetus venerealis strains are either absent from, or
      present at clinically insignificant levels of endemicity among, beef breeding
      herds in New Zealand. CLINICAL SIGNIFICANCE: The real-time PCR assay that was
      assessed in this study should not be used for the detection of C. fetus
      venerealis in bulls or for investigations of low conception rates in cattle in
      New Zealand. During the course of this survey, sequencing analysis of an apparent
      C. fetus venerealis isolate from the intestines of a Friesian bull turned out to
      be Campylobacter hyointestinalis. As a consequence, this real-time PCR assay for
      C. fetus venerealis is no longer being offered by diagnostic laboratories in New
      Zealand.

PMID- 24580099
TI  - War and HIV: sex and gender differences in risk behaviour among young men and
      women in post-conflict Gulu District, Northern Uganda.
AB  - Despite growing knowledge of the dynamics of HIV infection during conflict, far
      less is known about the period that follows cessation of hostilities and its
      implications for population health. This study sought to fill a lacuna in
      epidemiological evidence by examining HIV infection and related vulnerabilities
      of young people living in resource-scarce, post-emergency transit camps that are
      now home to thousands of displaced people following two decades of war in
      northern Uganda. In 2010, a cross-sectional demographic and behavioural survey
      was conducted with 384 transit camp residents aged 15-29 years old in Gulu
      District. Biological specimens were collected for rapid and confirmatory HIV
      testing. Separate multivariable logistic regression models by sex identified risk
      factors for HIV infection. HIV prevalence was 15.6% (95% confidence interval
      [CI]: 10.8%, 21.6%) among females and 9.9% (95% CI: 6.1%, 15.0%) among males. The
      strongest correlate of HIV infection among men was a non-consensual sexual debut
      (adjusted odds ratio [AOR] 3.24; 95% CI: 1.37-7.67), and having practiced dry sex
      (AOR 7.62; 95% CI: 1.56-16.95) was the strongest correlate among women. Conflict
      affected men and women experience vulnerability to HIV infection in different
      ways than may have originally been understood. Post-conflict programme planners
      must therefore design and implement contextualised, evidence-based responses to
      HIV that are sensitive to gender and cultural issues.

PMID- 24580100
TI  - Simplified molecular input line entry system-based optimal descriptors: QSAR
      modelling for voltage-gated potassium channel subunit Kv7.2.
AB  - CORAL software has been used to build quantitative structure-activity
      relationships (QSARs) for the prediction of binding affinities (pEC50, i.e.,
      minus decimal logarithm of the 50% effective concentration) of 35 potent
      inhibitors towards the voltage-gated potassium channel subunit Kv7.2. The pEC50
      has been modelled using eight random splits, with the following representations
      of the molecular structure: (i) hydrogen-suppressed graph (HSG); (ii) simplified
      molecular input line entry system (SMILES); (iii) graph atomic orbitals (GAOs)
      and (iv) hybrid representation, which is HSG together with SMILES. These models
      have been examined using three methods, the classic scheme, balance correlation,
      and balance correlation with ideal slope. The QSAR model based on single optimal
      descriptors using SMILES provided the best accuracy for the prediction of the
      pEC50. The robustness of these models has been checked using parameters such as
      rm(2), r(*)m(2), [Formula: see text], and using a randomization technique. The
      best QSAR model based on single optimal descriptors has been applied to study the
      in vitro structure-activity relationships of pyrazolo[1,5-a]pyrimidin-7(4H)-one
      derivatives as Kv7.2 modulators. The pEC50 is found to be significantly increased
      by the incorporation of -OH, -NO2 or -Br groups in place of one -F, whereas -NH2
      has a negative effect on the pEC50 values. 

PMID- 24580103
TI  - Helicenes from diarylmaleimides.
AB  - Perkin condensations of arylglyoxylic acids with arylacetic acids, followed by
      the addition of alkylamine, yield diarylmaleimides in a one-pot procedure. The
      arylglyoxylic acids are obtained by arene acylation with ClCOCO2Et and reduced
      with NaI and hypophosphorous acid to the arylacetic acids. With 2,7-di-tert-butyl
      pyren-4-yl or chrysen-6-yl as the aryl, photocyclodehydrogenation of the
      diarylmaleimides yields substituted helicenes which can be reduced to stable
      anions. The helicenes combine bathochromically shifted absorption with
      hypsochromically shifted fluorescence with respect to their precursors. 

PMID- 24580101
TI  - Root jasmonic acid synthesis and perception regulate folivore-induced shoot
      metabolites and increase Nicotiana attenuata resistance.
AB  - While jasmonic acid (JA) signaling is widely accepted as mediating plant
      resistance to herbivores, and the importance of the roots in plant defenses is
      recently being recognized, the role of root JA in the defense of above-ground
      parts remains unstudied. To restrict JA impairment to the roots, we micrografted
      wildtype Nicotiana attenuata shoots to the roots of transgenic plants impaired in
      JA signaling and evaluated ecologically relevant traits in the glasshouse and in
      nature. Root JA synthesis and perception are involved in regulating nicotine
      production in roots. Strikingly, systemic root JA regulated local leaf JA and
      abscisic acid (ABA) concentrations, which were associated with differences in
      nicotine transport from roots to leaves via the transpiration stream. Root JA
      signaling also regulated the accumulation of other shoot metabolites; together
      these account for differences in resistance against a generalist, Spodoptera
      littoralis, and a specialist herbivore, Manduca sexta. In N. attenuata's native
      habitat, silencing root JA synthesis increased the shoot damage inflicted by
      Empoasca leafhoppers, which are able to select natural jasmonate mutants.
      Silencing JA perception in roots also increased damage by Tupiocoris notatus. We
      conclude that attack from above-ground herbivores recruits root JA signaling to
      launch the full complement of plant defense responses.

PMID- 24580102
TI  - A meta-analysis of ethnic differences in pathways to care at the first episode of
      psychosis.
AB  - OBJECTIVE: We sought to systematically review the literature on ethnic
      differences in the likelihood of general practitioner (GP) involvement, police
      involvement, and involuntary admission on the pathway to care of patients with
      first-episode psychosis (FEP). METHOD: We searched electronic databases and
      conducted forward and backward tracking to identify relevant studies. We
      calculated pooled odds ratios (OR) to examine the variation between aggregated
      ethnic groups in the indicators of the pathway to care. RESULTS: We identified
      seven studies from Canada and England that looked at ethnic differences in GP
      involvement (n=7), police involvement (n=7), or involuntary admission (n=5).
      Aggregated ethnic groups were most often compared. The pooled ORs suggest that
      Black patients have a decreased likelihood of GP involvement (OR=0.70, 0.57-0.86)
      and an increased likelihood of police involvement (OR=2.11, 1.67-2.66), relative
      to White patients. The pooled ORs were not statistically significant for patients
      with Asian backgrounds (GP involvement OR=1.23, 0.87-1.75; police involvement
      OR=0.86, 0.57-1.30). There is also evidence to suggest that there may be ethnic
      differences in the likelihood of involuntary admission; however, effect
      modification by several sociodemographic factors precluded a pooling of these
      data. CONCLUSION: Ethnic differences in pathways to care are present at the first
      episode of psychosis.

PMID- 24580104
TI  - Drowning in children: Utstein style reporting and outcome.
AB  - BACKGROUND: We report the incidence and mortality of paediatric drowning
      incidents according to 'Utstein Style for Drowning' guidelines. METHODS:
      Retrospective study including all the drowned children under 16 years of age who
      were hospitalised or died with or without attempted cardiopulmonary resuscitation
      (CPR) between 1997 and 2007 in the province of Uusimaa, Finland. Survival rates
      provided at hospital discharge and after 1-year follow-up period are reported.
      RESULTS: A total of 58 drowned children were either admitted to the paediatric
      intensive care unit or died during the study period. The median (interquartile
      range) age was 5.9 (3.1, 7.8) years. The annual incidence of drowning was
      1.9/100,000 and was highest, 2.8/100,000, in children aged between 1 and 4 years.
      The annual mortality rate was 0.9/100,000. Of all the 58 patients, 14 (24%) died
      at the scene, 22 (38.1%) before the hospital discharge, and 26 (45%) within the 1
      year. The number of non-fatal drownings was 1.2-fold that of fatal drownings. The
      survival rate of the 26 patients for whom CPR was initiated by emergency medical
      service (EMS) personnel was 42% at hospital discharge, with the 1-year survival
      rate being 27%. CONCLUSIONS: The incidence of drowning in children and the
      survival rate of those children in whom CPR was initiated by EMS personnel was in
      line with the previously reported. However, the overall mortality rate in drowned
      children was higher than estimated in previous studies.

PMID- 24580105
TI  - Roles of different forms of lipopolysaccharides in Ralstonia solanacearum
      pathogenesis.
AB  - Lipopolysaccharides (LPS) are critical components for the fitness of most gram
      negative bacteria. Ralstonia solanacearum causes a deadly wilting disease in many
      crops; however, the pathogenic roles of different forms of LPS and their pathways
      of biogenesis remain unknown. By screening for phage-resistant mutants of R.
      solanacearum Pss4, whose genome sequence is unavailable, mutants with various
      types of structural defects in LPS were isolated. Pathogenesis assays of the
      mutants revealed that production of rough LPS (R-LPS), which does not contain O
      polysaccharides, was sufficient to cause necrosis on Nicotiana benthamiana and
      induce the hypersensitive response on N. tabacum. However, biosynthesis of smooth
      LPS (S-LPS), which contains O-polysaccharides, was required for bacterial
      proliferation at infection sites on N. benthamiana leaves and for proliferation
      and causing wilt on tomato. Complementation tests confirmed the involvement of
      the previously unidentified cluster RSc2201 to RSc2204 in the formation of R.
      solanacearum S-LPS. With these data and the availability of the annotated genomic
      sequence of strain GMI1000, certain loci involved in key steps of R. solanacearum
      LPS biosynthesis were identified. The strategy of this work could be useful for
      similar studies in other bacteria without available genome sequences. 

PMID- 24580106
TI  - Metabolic environments and genomic features associated with pathogenic and
      mutualistic interactions between bacteria and plants.
AB  - Genomic characteristics discriminating parasitic and mutualistic relationship of
      bacterial symbionts with plants are poorly understood. This study comparatively
      analyzed the genomes of 54 mutualists and pathogens to discover genomic markers
      associated with the different phenotypes. Using metabolic network models, we
      predict external environments associated with free-living and symbiotic
      lifestyles and quantify dependences of symbionts on the host in terms of the
      consumed metabolites. We show that specific differences between the phenotypes
      are pronounced at the levels of metabolic enzymes, especially carbohydrate
      active, and protein functions. Overall, biosynthetic functions are enriched and
      more diverse in plant mutualists whereas processes and functions involved in
      degradation and host invasion are enriched and more diverse in pathogens. A
      distinctive characteristic of plant pathogens is a putative novel secretion
      system with a circadian rhythm regulator. A specific marker of plant mutualists
      is the co-residence of genes encoding nitrogenase and ribulose bisphosphate
      carboxylase/oxygenase (RuBisCO). We predict that RuBisCO is likely used in a
      putative metabolic pathway to supplement carbon obtained heterotrophically with
      low-cost assimilation of carbon from CO2. We validate results of the comparative
      analysis by predicting correct phenotype, pathogenic or mutualistic, for 20
      symbionts in an independent set of 30 pathogens, mutualists, and commensals. 

PMID- 24580107
TI  - The fluorescence intermittency for quantum dots is not power-law distributed: a
      luminescence intensity resolved approach.
AB  - The photoluminescence (PL) of single emitters like semiconductor quantum dots
      (QDs) shows PL intermittency, often called blinking. We explore the PL
      intensities of single CdSe/ZnS QDs in polystyrene (PS), on polyvenylalcohol
      (PVA), and on silicon oxide (SiOx) by the change-point analysis (CPA). By this,
      we relate results from the macrotime (sub-ms to 1000 s) and the microtime (0.1
      100 ns) range to discrete PL intensities. We conclude that the intensity selected
      "on"-times in the ms range correspond to only a few (discrete) switching times,
      while the PL decays in the ns range are multiexponential even with respect to the
      same selected PL intensity. Both types of relaxation processes depend
      systematically on the PL intensity in course of a blinking time trace. The
      overall distribution of on-times does not follow a power law contrary to what has
      often been reported but can be compiled into 3-4 characteristic on-times. The
      results can be explained by the recently suggested multiple recombination centers
      model. Additionally, we can identify a well-defined QD state with a very low PL
      intensity above the noise level, which we assign to the strongly quenched exciton
      state. We describe our findings by a model of a hierarchical sequence of hole and
      electron trapping. Blinking events are the consequence of slow switching
      processes among these states and depend on the physicochemical properties of the
      heterogeneous nanointerface of the QDs. 

PMID- 24580108
TI  - Tuberculosis-immune reconstitution inflammatory syndrome in HIV: from
      pathogenesis to prediction.
AB  - Tuberculosis-immune reconstitution inflammatory syndrome (TB-IRIS) is an
      exaggerated, dysregulated immune response against dead or viable antigens of
      Mycobacterium tuberculosis that frequently occurs after initiation of
      antiretroviral therapy despite an effective suppression of HIV viremia.
      Scientific advances in IRIS pathogenesis have led researchers and clinicians to
      postulate risk factors that could possibly predict this syndrome, in an attempt
      to reduce the incidence and the severity of IRIS, with appropriate anti
      inflammatory therapy. This review is a summary of the available literature on
      pathogenic mechanisms involved from the macro to the micro level, the clinical
      spectrum, available predictors and the scope of these biomarkers to function as
      specific therapeutic targets, that could effectively modulate or ameliorate this
      syndrome in future.

PMID- 24580109
TI  - Fungus-associated asthma: overcoming challenges in diagnosis and treatment.
AB  - With regard to fungal colonization and fungal sensitization, the goals of fungus
      associated asthma management are as follows: 1) to survey fungi colonizing the
      airways of patients repeatedly; 2) to evaluate the tendency of the colonizing
      fungi to sensitize patients and the influence on clinical manifestations of
      asthma; 3) to follow disease development to allergic bronchopulmonary mycosis or
      sinobronchial allergic mycosis; and 4) to determine whether fungal eradication
      from the airway of patients is beneficial from the viewpoints of future risk
      factors. Recent developments in molecular biological analyses have facilitated
      the identification of basidiomycetous fungi that were not previously thought to
      be of concern in fungal allergy. The total control of fungus-associated asthma
      will be accomplished by environmental management established from the viewpoint
      of both the ecology and life cycle of the responsible fungi.

PMID- 24580110
TI  - Selective oxidation of arsenite by peroxymonosulfate with high utilization
      efficiency of oxidant.
AB  - Oxidation of arsenite (As(III)) is a critical yet often weak link in many current
      technologies for remediating contaminated groundwater. We report a novel,
      efficient oxidation reaction for As(III) conversion to As(V) using commercial
      available peroxymonosulfate (PMS). As(III) is rapidly oxidized by PMS with a
      utilization efficiency larger than 90%. Increasing PMS concentrations and pH
      accelerate oxidation of As(III), independent to the availability of dissolved
      oxygen. The addition of PMS enables As(III) to oxidize completely to As(V) within
      24 h, even in the presence of high concentrations of radical scavengers. On the
      basis of these observations and theoretical calculations, a two-electron transfer
      (i.e., oxygen atom transfer) reaction pathway is proposed. Direct oxidation of
      As(III) by PMS avoids the formation of nonselective reactive radicals, thus
      minimizing the adverse impact of coexisting organic matter and maximizing the
      utilization efficiency of PMS. Therefore, this simple approach is considered a
      cost-effective water treatment method for the oxidation of As(III) to As(V). 

PMID- 24580111
TI  - Experimental measurements and computational predictions of regional particle
      deposition in a sectional nasal model.
AB  - BACKGROUND: Knowledge of the regional deposition of inhaled particles in the nose
      is important for drug delivery and assessment of the toxicity of inhaled
      materials. In this study, computational fluid dynamics (CFD) predictions and
      experimental measurements in a nasal replica cast were used to study regional
      deposition of inhaled microparticles. METHODS: The replica cast was sectioned
      into six regions of interest based on nasal anatomy: the nasal vestibule, nasal
      valve, anterior turbinates, olfactory region, turbinates, and nasopharynx.
      Monodisperse fluorescein particles with aerodynamic diameters of 2.6-14.3 MUm
      were passed through the assembled cast in the presence of steady inspiratory
      airflow at 15 L/min. After each experiment, the cast was disassembled and the
      deposited fluorescein in each region was washed out and quantified with
      fluorescence spectrometry. A nasal CFD model was developed from the same magnetic
      resonance imaging scans that were used to construct the replica cast. Steady
      state inspiratory airflow and particle deposition calculations were conducted in
      the CFD model using Fluent(TM) at flow rates producing Stokes numbers comparable
      to experimental conditions. RESULTS: Total and regional particle deposition
      predictions from the CFD model were compared with experimental measurements from
      the replica cast. Overall, good agreement was observed between CFD predictions
      and experimental measurements with similar deposition trends in each region of
      interest. CFD predictions in central nasal regions demonstrated well-defined
      maximum values of 15%, 7%, and 12% in the anterior turbinates, olfactory, and
      turbinates regions, respectively, at particle sizes of 10-11 MUm. CONCLUSIONS:
      These results demonstrate the use of a sectioned nasal CFD model based on
      anatomical regions of interest for nasal drug delivery to elucidate patterns of
      regional deposition within a human nasal cavity.

PMID- 24580113
TI  - Advancing the peer review process: a multifaceted approach to improving quality.

PMID- 24580112
TI  - Protective effect of Mutellina purpurea polyphenolic compounds in doxorubicin
      induced toxicity in H9c2 cardiomyocytes.
AB  - The delayed cardiomyopathy caused by doxorubicin - an chemotherapeutic drug with
      broad spectrum of anticancer activity - is mainly triggered by oxidative stress.
      The aim of this study was to assess an effect of Mutellina purpurea methanolic
      extract fraction and other antioxidants of plant origin: rutin, quercetin and
      chlorogenic acid (all 1 mg% w/v) on oxidative stress and morphological changes
      induced by doxorubicin in cardiomyocytes H9c2. Mitochondrial oxidative stress in
      cardiomyocytes induced by 1 uM doxorubicin was evidenced by MitoTracker and
      RedoxSensor Red CC-1 dyes. Moreover, cardiomyocytes morphological changes and
      cell viability were evaluated. The tested fraction slightly reduced mitochondrial
      ROS fluorescence, similar to quercetin. Chlorogenic acid revealed concentration
      dependent prooxidative and antioxidative properties in the applied H9c2 model.
      The evaluation of the protective effect of tested compounds on doxorubicin
      induced cytotoxicity was based on the examination of induced oxidative stress and
      morphology changes. The protective effect was described in the following order:
      rutin > chlorogenic acid (0.5 uM) > LH8 and quercetin. According to the MTT test,
      rutin seems to be the most promising compound that should be tested in a future
      studies.

PMID- 24580114
TI  - Randomised controlled trials demonstrate efficacy of a novel internal teat
      sealant to prevent new intramammary infections in dairy cows and heifers.
AB  - AIMS: The main aim was to investigate the effectiveness of a novel internal teat
      sealant (ITS) formulation containing bismuth subnitrate and the antiseptic
      chlorhexidine, in adult cows (Trial A) and nulliparous heifers (Trial B), to
      reduce the incidence of new intramammary infection (IMI) between treatment and
      calving and reduce the prevalence of IMI within 6 days following calving.
      METHODS: In Trial A dairy cows (n=326) without history of clinical mastitis and
      with a maximum composite milk somatic cell count <200,000 cells/mL during the
      current lactation were enrolled from three spring-calving mainly pasture-based
      herds immediately following the final milking. In Trial B all heifers (n=166)
      were enrolled from two herds approximately 3 weeks before the start of calving.
      Glands were randomly assigned to controls or treatment with ITS, and mammary
      secretion samples were taken from all glands prior to treatment, and on two
      occasions 0-4 and 3-6 days post-calving to determine the incidence of new IMI and
      the prevalence of IMI immediately post-calving. Additionally, cows in Trial A
      were monitored for cases of clinical mastitis (CM) in the non-lactating period
      and animals in both trials were monitored for cases of CM within 30 days of
      calving. RESULTS: The ITS reduced the estimated incidence of new IMI with both
      major and any pathogens compared to control glands in cows (6.2 vs. 14.2% and
      14.7 vs. 32.8%, respectively) and in heifers (3.0 vs. 13.1% and 13.4 vs. 25.3%,
      respectively) (p<0.001). The ITS reduced the estimated prevalence of a major or
      any pathogen compared to untreated controls at both 0-4 and 3-6 days post
      calving, in both cows and heifers. Additionally, the ITS reduced the incidence of
      CM in the non-lactating period in cows (-1.0%, p=0.01) and in the 30 days
      following calving in heifers (-2.0%, p=0.06), and tended to reduce the estimated
      incidence of CM in cows post-calving (-1.7%, p=0.10). CONCLUSIONS: The novel ITS
      reduced the incidence of new IMI, and the prevalence of IMI at calving in both
      adult cows and heifers, and reduced the incidence of CM in the non-lactating
      period of cows and in the first 30 days after calving in heifers. CLINICAL
      RELEVANCE: The results of these trials demonstrate the efficacy of a novel ITS
      for the control of mastitis in likely uninfected dairy cows over the non
      lactating period and in heifers in late pregnancy.

PMID- 24580115
TI  - On the role of the appended P19 element in type A RNAs of bacterial RNase P.
AB  - Comparative in silico analyses of bacterial RNase P enzymes clustered their RNA
      subunits in type A RNA, found in Escherichia coli, and in type B, found in
      Bacillus subtilis. Zymomonas mobilis RNase P consists of one protein (Zmo-RnpA)
      and one type A RNA (RPR) subunit containing the P19 element, present in many
      RNase P RNAs of any structure class but lacking in the E. coli RNase P RNA. To
      investigate the putative role of the P19 stem, we constructed a P19 deletion RNA
      mutant (DeltaP19RPR) and performed detailed kinetic analysis of reconstituted
      enzymes in the presence of the homologous Zmo-RnpA protein or Eco-RnpA protein
      from E. coli. The deletion of P19 perturbs the monovalent ion requirements. The
      Mg(2+) requirement for the DeltaP19RPR holoenzyme was almost identical to that
      for the wtRPR holoenzyme at Mg(2+) concentrations of <=25 mM. Interestingly,
      enzymes reconstituted with Eco-RnpA protein, relative to those assembled with Zmo
      RnpA, exhibited enhanced activity in the presence of DeltaP19RPR, suggesting that
      Eco-RnpA protein can effectively replace its Z. mobilis counterpart. Homologous
      and heterologous reconstituted enzymes in the presence of DeltaP19RPR exhibited
      differences in their Km values and catalytic efficacies. Overall, the presence of
      the P19 stem points toward an adaption during the co-evolution of Zmo-RnpA and
      RPR that is essential for stabilizing the overall structure of the Z. mobilis
      RNase P. Finally, our results are in line with existing structural data on RNase
      P enzymes and provide biochemical support for the possible role of appended
      domains in RNase P RNA subunits. 

PMID- 24580116
TI  - Origin of the electrocatalytic oxygen reduction activity of graphene-based
      catalysts: a roadmap to achieve the best performance.
AB  - The mutually corroborated electrochemical measurements and density functional
      theory (DFT) calculations were used to uncover the origin of electrocatalytic
      activity of graphene-based electrocatalysts for oxygen reduction reaction (ORR).
      A series of graphenes doped with nonmetal elements was designed and synthesized,
      and their ORR performance was evaluated in terms of four electrochemical
      descriptors: exchange current density, on-set potential, reaction pathway
      selectivity and kinetic current density. It is shown that these descriptors are
      in good agreement with DFT calculations, allowing derivation of a volcano plot
      between the ORR activity and the adsorption free energy of intermediates on metal
      free materials, similarly as in the case of metallic catalysts. The molecular
      orbital concept was used to justify this volcano plot, and to theoretically
      predict the ORR performance of an ideal graphene-based catalyst, the ORR activity
      of which is comparable to the state-of-the-art Pt catalyst. Moreover, this study
      may stimulate the development of metal-free electrocatalysts for other key energy
      conversion processes including hydrogen evolution and oxygen evolution reactions
      and largely expand the spectrum of catalysts for energy-related electrocatalysis
      reactions. 

PMID- 24580117
TI  - Physiological response of fucoid algae to environmental stress: comparing range
      centre and southern populations.
AB  - Climate change has led to alterations in assemblage composition. Species of
      temperate macroalgae at their southern limits in the Iberian Peninsula have shown
      shifts in geographical range and a decline in abundance ultimately related to
      climate, but with the proximate factors largely unknown. We performed
      manipulative experiments to compare physiological responses of Fucus vesiculosus
      and Fucus spiralis from Portugal and Wales (UK), representing, respectively,
      southern and central areas of their distribution, to different intensities of
      solar radiation and different air temperatures. Following exposure to stressful
      emerged conditions, Portuguese and Welsh individuals of both fucoid species
      showed increased frond temperature, high desiccation levels and reduced
      photophysiological performance that was evident even after a 16 h recovery
      period, with light and temperature acting in an additive, not an interactive,
      manner. The level of physiological decline was influenced by geographical origin
      of populations and species identity, with algae from the south and those living
      higher on the shore coping better with stressful conditions. The negative effect
      of summer conditions on photophysiology may contribute to changes in fucoid
      abundance and distribution in southern Europe. Our results emphasise how
      physiological performance of geographically distinct populations can differ,
      which is particularly relevant when predicting responses to climate change.

PMID- 24580118
TI  - Global pharmacogenomics: where is the research taking us?
AB  - Pharmacogenomics knowledge and technologies, which couple genomics information
      with pharmaceutical drug response, have been promised to revolutionise both drug
      development and prescription. One notable promise of pharmacogenomics is the
      potential to contribute to some of the Millennium Development Goals (MDGs),
      namely to increase justice in global health by incentivising public research
      laboratories and pharmaceutical companies to develop drugs for populations (e.g.,
      in low- and middle-income countries) that have been neglected by the traditional
      drug development model. To evaluate the credibility of this promise, we examined 
      both quantitatively and qualitatively - those scientific papers indexed in
      PubMed and published between 1997 and 2010, with a view to describing the major
      orientations and tendencies characterising the development of pharmacogenomics
      research. Our results demonstrate that pharmacogenomics research has focused on
      three major non-communicable categories of disease: cancer, depression and other
      psychological disorders and cardiovascular and coronary heart disease. Few
      publications - and thus, by extension, little scientific interest - concerned
      orphan diseases, infectious diseases or maternal health, indicating that
      pharmacogenomics research over the last decade has replicated the well-known
      90/10 ratio in drug development. As such, we argue that research in the field of
      pharmacogenomics has failed in its promise to contribute to the MDGs by reducing
      global health inequalities. 

PMID- 24580119
TI  - The relationship between Big-5 personality traits and cognitive ability in older
      adults - a review.
AB  - It is well established that fundamental aspects of cognition such as memory and
      speed of processing tend to decline with age; however, there is substantial
      between-individual variability in levels of cognitive performance in older
      adulthood and in rates of change in cognitive abilities over time. Recent years
      have seen an increasing number of studies concerned with examining personality
      characteristics as possible predictors of some of this variability in cognitive
      aging. The purpose of this article is to review the literature, and identify
      patterns of findings regarding the relationships between personality (focusing on
      the Big-5) and cognitive ability across nonclinical populations of older adults.
      Possible mechanisms underlying associations of personality characteristics with
      cognition are reviewed, and assessed in the context of the current literature.
      Some relatively consistent relationships are identified, including positive
      associations between openness and cognitive ability, and associations of
      conscientiousness with slower rates of cognitive decline. However, the
      relationships between several personality traits and cognitive abilities in older
      adults remain unclear. We suggest some approaches to research design and analysis
      that may help increase our understanding of how personality differences may
      contribute to cognitive aging. 

PMID- 24580120
TI  - The power of r - pharmaceutical sales decomposition in Cyprus public healthcare
      sector and determinants of drug expenditure evolution: any lessons learned?
AB  - The pharmaceutical sector has been established as the primary cost driver in
      health. The scope of this paper is to explore the drivers of pharmaceutical
      expenditure in Cyprus by decomposing sales and assessing impact of prices,
      volumes and substitution effect. We used a statistical approach to decompose the
      growth of public pharmaceutical expenditure during 2005-2011 into three elements:
      1) substitution effect; 2) price effect; and 3) increase of consumption. We
      further decomposed consumption into: 1) prescription/visits; 2)
      visits/beneficiaries; and 3) beneficiaries. Pharmaceutical expenditure grew by
      31.4 % and volume of medicines dispensed increased by 55%. Prices declined by 11%
      and product-mix residual was -5.5%, indicating that Cyprus experienced a switch
      to cheaper medicines (generics) without compromising access of patients to
      innovative medicines. This was enhanced by guidelines, monitoring of prescribing
      behavior, generic substitution and efficient tendering. The increasing number of
      products per prescriptions should be monitored with caution. 

PMID- 24580121
TI  - Interleukin levels and their potential association with venous thromboembolism
      and survival in cancer patients.
AB  - Cytokines have been found to be elevated in cancer patients and have been
      associated with worse prognosis in single tumour entities. We investigated the
      association of eight different cytokines with venous thromboembolism (VTE) and
      prognosis in cancer patients. The Vienna Cancer and Thrombosis Study (CATS), a
      prospective study, includes patients with newly diagnosed tumour or disease
      progression. Patients with an overt infection are excluded. Study end-points are
      VTE, death, loss to follow-up or study completion. Interleukin (IL) serum levels
      were measured using the xMAP technology developed by Luminex. Among 726 included
      patients, no associations between IL levels and VTE were found, with the
      exception of a trend for IL-1beta and IL-6 in pancreatic cancer. Elevated levels
      of IL-6 [as continuous variable per double increase hazard ratio (HR) = 1.07, 95%
      confidence interval (CI) = 1.027-1.114, P = 0.001, IL-8 (HR = 1.12, 95% CI =
      1.062-1.170, P < 0.001) and IL-11 (HR = 1.37, 95% CI = 1.103-1.709, P = 0.005]
      were associated with worse survival. In subgroup analyses based on tumour type,
      colon carcinoma patients, who had higher IL-6 levels, showed a shorter survival
      (HR = 2.405, 95% CI = 1.252-4.618, P = 0.008). A significant association of
      elevated IL-10 levels with a decrease in survival (HR = 1.824, 95% CI = 1.098
      3.031, P = 0.020) was seen among patients with lung cancer. No correlation
      between VTE and IL levels was found, but higher IL-6, IL-8 and IL-11 levels were
      associated with worse survival in cancer patients. Further, elevated IL-6 levels
      might be a prognostic marker in colorectal cancer and elevated IL-10 levels in
      lung cancer patients. 

PMID- 24580122
TI  - GANRA-5 protects both cultured cells and mice from various radiation types by
      functioning as a free radical scavenger.
AB  - The radio-protective effects of the oxazolone derivative chemical compound 4-(4
      methoxy-3-methoxyphenyl-methyl)-2-phenyl- 5(4H)-oxazolone (GANRA-5) against
      different types of radiation including X-rays, carbon ion beams, microwaves and
      ultraviolet light (UV) were studied. Cell proliferation/cytotoxicity assay and
      colony-forming assay were conducted to evaluate the toxicity of GANRA-5. To test
      its influence on the induction of double-stranded break (DSB) formation and
      genomic instability, gammaH2AX focus-forming assay as well as cytokinesis-block
      micronucleus assay was utilized. Our results indicate that GANRA-5 exhibits low
      toxicity, while providing high radio-protective effects for MRC-5 cells against
      different types of radiation. We also found that GANRA-5 acts as a free radical
      scavenger. Our animal studies provided evidence that GANRA-5 significantly
      increases the survival rate of mice after X-ray irradiation. Analyses of
      hemogram, visceral index and detection of superoxide dismutase (SOD) and
      malondialdehyde (MDA) in the viscera indicate both low toxicity of GANRA-5,
      combined with its ability to shield radiation risk. In conclusion, our results
      suggest that GANRA-5 has the potential to be used as a safe and efficient radio
      protectant.

PMID- 24580123
TI  - Three-component Povarov reaction-heteroannulation with arynes: synthesis of 5,6
      dihydroindolo[1,2-a]quinolines.
AB  - A reaction of 2-acyl substituted tetrahydroquinolines, prepared by Lewis acid
      catalyzed three-component reaction of alpha-oxo aldehydes, anilines, and
      dienophiles, with in situ generated arynes afforded 5,6-dihydroindolo[1,2
      a]quinolines in good to excellent yields. 

PMID- 24580124
TI  - Effect of otitis media with effusion and its clinical intervention on the
      development of mastoid in children.
AB  - CONCLUSION: Otitis media with effusion (OME) can affect the development of
      mastoid in children. For younger children (<12 years old), surgical intervention
      may promote the development of mastoid. It is highly recommended that patients
      with severe tympanic membrane retraction have tympanostomy tubes to improve the
      circulation in the middle ear as early as possible. OBJECTIVE: To investigate the
      effect of OME and its clinical intervention on the development of mastoid in
      children. METHODS: A total of 46 children with OME were divided into 2 groups
      according to their ages. In group 1, 26 cases (0-6 years old) were treated for
      approximately 2 months, while in group 2, 20 cases (7-15 years old) were treated
      for 10 months. The treatments included tympanic effusion incision or
      catheterization, and adenoidectomy and/or bilateral tonsillectomy. Before and 6
      months after treatments, patients were examined by bilateral temporal bone CT
      scanning, pure-tone audiometry, and tympanometry. 3-D volumetric reconstruction
      was then performed to determine the morphological properties of each patient's
      mastoid. RESULTS: After a 2-month comprehensive treatment, the volume of mastoid
      was close to that in normal children, indicating that it could return to normal
      level if the treatment was completed within 2 months. In group 2, the results
      suggested that if the treatment lasted more than 6 months, the development of
      mastoid would be stalled.

PMID- 24580126
TI  - Univariate and multivariate analyses for postoperative bleeding after nasal
      endoscopic surgery.
AB  - CONCLUSIONS: Our study suggested that the major risk factors for postoperative
      bleeding after nasal endoscopic surgery (NES) included hypertension, long-term
      non-steroidal anti-inflammatory drugs (NSAIDs), and previous nasal surgery. The
      use of preoperative corticosteroids is a valuable measure for reducing
      postoperative bleeding after NES. OBJECTIVES: To explore risk factors for
      postoperative bleeding after NES and find effective measures to reduce or prevent
      the condition. METHODS: A total of 641 patients who underwent NES were analyzed
      retrospectively. Univariate analysis and logistic regression were performed to
      find potential risk factors. RESULTS: The incidence of postoperative bleeding
      after NES was 8.4%. Multivariate logistic regression analysis revealed that the
      occurrence of postoperative bleeding after NES was positively associated with
      hypertension, long-term NSAIDs, previous NES, and modified submucosal
      septoplasty, but negatively associated with the use of preoperative
      corticosteroids.

PMID- 24580125
TI  - Kinetic oscillation stimulation as treatment of non-allergic rhinitis: an RCT
      study.
AB  - CONCLUSION: Kinetic oscillation stimulation (KOS) of nasal mucosa at low
      frequency seems to be a possibly effective and safe short-term treatment of non
      allergic nasal stuffiness. OBJECTIVE: To assess the relief of rhinitis symptoms,
      especially stuffiness, by comparing active treatment, i.e. KOS at low frequency
      of the nasal mucosa, with placebo. METHODS: Patients were randomized to active or
      placebo treatment in this double-blinded parallel design study. Treatment with an
      inflatable oscillating catheter was administered on day 0, and symptom scores
      (stuffiness, secretion, and itching) were graded daily until day 14. An overall
      grading of symptoms from 1 week before treatment and during 14 days thereafter
      was made at day 14. Eighty-six patients (52 with non-allergic perennial rhinitis,
      NAR; 34 with rhinitis medicamentosa, RM) were randomized, and 71 were evaluated
      (active treatment, n = 35; placebo, n = 36). RESULTS: Patients with either NAR or
      RM who received active treatment reported reduced symptom scores by some
      measures, e.g. median RQSS stuffiness measure fell from 2 to 1 on a scale from 0
      to 3 during the week following treatment. No significant effect was observed for
      patients treated with placebo. Mild side effects were reported.

PMID- 24580129
TI  - Photosensitive polyamines for high-performance photocontrol of DNA higher-order
      structure.
AB  - Polyamines are small, ubiquitous, positively charged molecules that play an
      essential role in numerous biological processes such as DNA packaging, gene
      regulation, neuron activity, and cell proliferation. Here, we synthesize the
      first series of photosensitive polyamines (PPAs) and demonstrate their ability to
      photoreversibly control nanoscale DNA higher-order structure with high
      efficiency. We show with fluorescence microscopy imaging that the efficiency of
      the PPAs as DNA-compacting agents is directly correlated to their molecular
      charge. Micromolar concentration of the most efficient molecule described here, a
      PPA containing three charges at neutral pH, compacts DNA molecules from a few
      kilobase pairs to a few hundred kilobase pairs, while subsequent 3 min UV
      illuminations at 365 nm triggers complete unfolding of DNA molecules. Additional
      application of blue light (440 nm for 3 min) induces the refolding of DNA into
      the compact state. Atomic force microscopy reveals that the compaction involves a
      global folding of the whole DNA molecule, whereas UV-induced unfolding is a
      modification initiated from the periphery of the compacted DNA, resulting in the
      occurrence of intermediate flower-like structures prior to the fully unfolded
      state. 

PMID- 24580130
TI  - Singly occupied MOs in mono- and diradical conjugated hydrocarbons: comparison
      between variational single-reference, pi-fully correlated and Huckel
      descriptions.
AB  - This work compares three descriptions of the unpaired electrons distribution in
      conjugated monoradical and diradical hydrocarbons involving one or two methylene
      groups attached to an aromatic skeleton. The first one is the simple Huckel
      topological Hamiltonian, the singly occupied molecular orbitals (SOMO) of which
      may be analytically obtained. The second one is the restricted open-shell self
      consistent field (ROHF-SCF) method. The so-obtained distribution of the unpaired
      electrons on the skeleton appears deeply different from that predicted by the
      Huckel Hamiltonian, being more strongly localized on the external methylene
      groups. More elaborate methods treat all pi electrons in the pi valence molecular
      orbitals (MOs) through a full valence pi complete active space self-consistent
      field (CASSCF) treatment. The distributions of the unpaired electrons (given by
      the natural MOs of occupation number close to 1) are surprisingly similar to
      those predicted by the Huckel model. The spin density distributions, including
      spin polarization effects, can be improved by further configuration interactions
      involving one hole-one particle excitations and compared with the experimental
      hyperfine coupling constant ratios. This comparison confirms the lack of
      delocalization of the magnetic orbitals defined from the self-consistent single
      reference treatment. We show that, provided correct SOMO are used, a single
      excitation CI performed on top of a single reference gives accurate spin
      densities. Finally, a rationalization of the role of the dynamic correlation in
      correcting the excessive localization of the unpaired electron(s) at the ROHF
      level on the exocyclic methylene group(s) is given, attributing it to the dynamic
      charge polarization of the charge transfer configurations between methylene and
      the aromatic frame. 

PMID- 24580127
TI  - 'It means there is doubt in the house': perceptions and experiences of HIV
      testing in rural Malawi.
AB  - Research on HIV testing decision-making overlooks a complex array of
      interpersonal factors that go beyond HIV risk and extend into the realms of
      intimacy, love and marriage. The current study draws upon two sets of qualitative
      data, semi-structured interviews and focus-group discussions, to investigate how
      romantic relationships shape HIV testing perceptions and experiences in rural
      Malawi. It invokes the classical works of symbolic interactionism to frame how
      people create meaning around the act of HIV testing that fits with their everyday
      lives. Pre-marital HIV testing was considered an acceptable method to confirm a
      partner's trustworthiness and commitment to the relationship. However, during
      marriage, a spontaneous discussion of HIV testing signified a breach of fidelity
      or that a partner could not be trusted. This belief was transposed such that an
      HIV test could also be used to confirm a person's moral character in the face of
      infidelity accusations and gossip. Thus, HIV testing during marriage was labelled
      as an unusual event, one reserved for special or problematic circumstances,
      rather than for regular screening of disease. A discussion of how these findings
      can inform HIV testing programmes and policy in sub-Saharan Africa is provided. 

PMID- 24580128
TI  - Induction of hepatitis B virus surface antigen-specific cytotoxic T lymphocytes
      can be up-regulated by the inhibition of indoleamine 2, 3-dioxygenase activity.
AB  - Cytotoxic T lymphocytes (CTLs) are thought to be major effectors involved in
      viral clearance during acute infections, including hepatitis B virus (HBV)
      infection. A persistent HBV infection is characterized by a lack of or a weak CTL
      response to HBV, which may be reflective of tolerance to HBV. Efficient induction
      of HBV-specific CTLs leads to the clearance of HBV in patients with a chronic HBV
      infection. Previously, we reported that alpha-galactosylceramide (alpha-GalCer),
      a specific natural killer T (NKT) cell agonist, enhanced the induction of HBV
      surface antigen (HBsAg)-specific CTLs. In the present study, we found that
      inhibition of indoleamine 2,3-dioxygenase (IDO) activity enhanced the induction
      of HBsAg-specific CTLs after immunization with HBsAg and alpha-GalCer. The
      administration of HBsAg and alpha-GalCer increased the production of interleukin
      2 and interleukin-12b, which are crucial for the induction of HBsAg-specific
      CTLs. The production of these cytokines was more strongly enhanced in IDO
      knockout mice compared with wild-type mice. In addition, alpha-GalCer induced the
      production of IDO in CD11b(+) cells, and these cells inhibited proliferation of
      HBsAg-specific CTLs. Our results lead to strategies for improving the induction
      of HBsAg-specific CTLs. 

PMID- 24580131
TI  - Immunohistochemical characterization of non-epithelial cells in spiradenoma.
AB  - Spiradenoma is unique with respect to the presence of a large number of non
      epithelial cells, including S100 protein(+) cells, most of which are presumably
      Langerhans cells, in the parenchyma as shown in the published work. However, the
      characterization of these non-epithelial cells to date is insufficient.
      Immunohistochemistry of CD1a, CD3, CD4, CD8, CD56, CD68, intercellular adhesion
      molecule-1 (ICAM-1), and HLA-DR, as well as double-immunofluorescence labeling of
      S100 protein/CD1a and CD1a/CD3, was performed using paraffin-embedded specimens
      from five cases of spiradenoma retrospectively. Non-epithelial cells evenly
      distributed throughout the parenchyma of spiradenoma primarily consisted of
      CD1a(+) Langerhans cells and CD3(+) T cells. ICAM-1 was expressed by epithelial
      cells and non-epithelial cells in the parenchyma. HLA-DR on the epithelial cells
      was limited to the focal area. In double-immunofluorescence labeling,
      approximately one-half of Langerhans cells were spatially related to T cells in
      the parenchyma, suggesting their functional interaction. 

PMID- 24580132
TI  - Activation of transient receptor potential melastatin 8 reduces ultraviolet B
      induced prostaglandin E2 production in keratinocytes.
AB  - Transient receptor potential melastatin 8 (TRPM8) is a member of the TRP family,
      and is activated at temperatures below 22 degrees C, or by cooling compounds such
      as menthol. In this study, it was found that a new role of TRPM8 activation on
      prostaglandin E2 (PGE2), an inflammatory cytokine and dendritogenesis stimulator
      of normal human melanocytes. Normal human keratinocytes were pretreated with
      menthol or incubated at 22 degrees C for TRPM8 activation before ultraviolet (UV)
      B irradiation. To examine the specificity between TRPM8 activation and PGE2
      release, we inhibited TRPM8 with the antagonist (capsazepine), or introduced
      TRPM8 siRNA for a gene silencing experiment. UV-B irradiation significantly
      induced PGE2 release in normal human keratinocytes. Interestingly, activation of
      TRPM8 at 22 degrees C or with menthol inhibited UV-B-induced PGE2 release. The
      effect of the TRPM8 agonist was completely blocked by pretreatment with the TRPM8
      antagonist, capsazepine. When TRPM8 expression was suppressed by siRNA, UV-B
      irradiation still upregulated PGE2 in keratinocytes, but pretreatment of menthol
      or low temperature did not inhibit UV-B-induced PGE2. In conclusion, the
      activation of TRPM8 inhibits UV-B-induced PGE2 production in keratinocytes, and
      the activation of TRPM8 may reduce inflammatory responses in skin. 

PMID- 24580133
TI  - Partner violence and abortion characteristics.
AB  - We conducted a retrospective cohort study using randomly selected medical charts
      of women reporting a history of partner violence and women with no history of
      partner violence at the time of a family planning or abortion appointment (n =
      6,564 per group). We analyzed lifetime history of partner violence for odds of
      lifetime history of abortion and miscarriage number, and birth control problems.
      To more closely match timing, we analyzed a subsample of 2,186 women reporting
      current violence versus not at the time of an abortion appointment for
      differences in gestational age, medical versus surgical method choice, and return
      for follow-up visit. After adjusting for years at risk and demographic
      characteristics, women with a past history of partner violence were not more
      likely to have ever had one abortion, but they were more likely to have had
      problems with birth control, repeat abortions, and miscarriages than women with
      no history of violence. Women with current partner violence were also more likely
      to be receiving an abortion at a later gestational age. We found no differences
      between the groups in return for abortion follow-up visit or choice of surgical
      versus medication abortion. Findings support screening for the influence of
      partner violence on reproductive health and related safety planning. 

PMID- 24580134
TI  - Concomitant use of argatroban and warfarin during hemodialysis in heparin-induced
      thrombocytopenia.
AB  - OBJECTIVE AND IMPORTANCE: The use of argatroban during hemodialysis in a patient
      receiving warfarin is not established. We present a case of heparin-induced
      thrombocytopenia in a patient on hemodialytic therapy who successfully received
      argatroban concomitantly to warfarin during renal replacement therapy. CLINICAL
      PRESENTATION: A 46-year-old male patient with autosomal dominant polycystic
      kidney disease presented with heparin-induced thrombocytopenia (HIT) arised
      during dialytic procedures. Intervention After the acute episode requiring
      argatroban and warfarin therapy, the patient continued to receive argatroban
      during the hemodialytic session concomitantly to warfarin. CONCLUSION: The
      administration of argatroban in the dialytic circuit of a patient on oral
      anticoagulant therapy can be considered an effective and safe approach.

PMID- 24580135
TI  - The reported contributions provide an excellent illustration of the wide range of
      scientific issues covered and the vitality of the photochemical activities in
      South America.

PMID- 24580136
TI  - Special issue dedicated to the memory of Elsa Beatriz Abuin Saccomano (1942
      2012).
AB  - In memoriam of Elsa Abuin (1942-2012), teacher, mentor and friend. This Special
      Issue presents a collection of review articles and papers dedicated to the memory
      of Elsa Abuin and most of them presented during the Meeting of the Latin-American
      photochemists (Encuentro Latino-Americano de Fotoquimica y Fotobiologia, ELAFOT)
      held in October 2012 in Cordoba, Argentina. 

PMID- 24580138
TI  - Low-level environmental tobacco smoke exposure and inflammatory biomarkers in
      children with asthma.
AB  - OBJECTIVE: The effects of low-level environmental tobacco smoke (ETS) exposure,
      on asthma control, lung function and inflammatory biomarkers in children with
      asthma have not been well studied. The objective of the study was to assess ETS
      exposure in school-age children with asthma whose parents either deny smoking or
      only smoke outside the home, and to assess the impact of low-level ETS exposure
      on asthma control, spirometry and inflammatory biomarkers. METHODS: Forty
      patients age 8-18 years with well-controlled, mild-to-moderate persistent asthma
      treated with either inhaled corticosteroids (ICS) or montelukast were enrolled.
      Subjects completed an age-appropriate Asthma Control Test and a smoke exposure
      questionnaire, and exhaled nitric oxide (FeNO), spirometry, urinary cotinine and
      leukotriene E(4) (LTE(4)) were measured. ETS-exposed and unexposed groups were
      compared. RESULTS: Only one parent reported smoking in the home, yet 28 (70%)
      subjects had urinary cotinine levels >=1 ng/ml, suggesting ETS exposure. Seven
      subjects (18%) had FeNO levels >25parts per billion, six of whom were in the ETS
      exposed group. In the ICS-treated subjects, but not in the montelukast-treated
      subjects, ETS exposure was associated with higher urinary LTE(4), p = 0.04, but
      had no effect on asthma control, forced expiratory volume in 1 s or FeNO.
      CONCLUSIONS: A majority of school-age children with persistent asthma may be
      exposed to ETS, as measured by urinary cotinine, even if their parents insist
      they don't smoke in the home. Urinary LTE(4) was higher in the ETS-exposed
      children treated with ICS, but not in children treated with montelukast.

PMID- 24580140
TI  - Calculation procedures and HPLC method for analysis of the lipophilicity of
      acyclovir esters.
AB  - Acyclovir (ACV) belongs to a class of drugs with low bioavailability. Selected
      ACV esters including acetyl (Ac-), isobutyryl (iBut-), pivaloyl (Piv-),
      ethoxycarbonyl (Etc-) and nicotinoyl (Nic-) were synthesized, and their
      lipophilicity was determined by the high-performance liquid chromatography (HPLC)
      RP method. Statistical analyses of the comparative values of log P and clog P
      were carried out using computational methods. It was proved that the AC log P
      algorithm can be useful for the analysis of these compounds and has a
      statistically justified application in the assessment of the quantitative
      structure-activity relationship. Moreover, the lipophilicity determined by the
      HPLC method appears as follows: ACV < Ac- < Nic- < Etc- < iBut- < Piv-. 

PMID- 24580141
TI  - Intramolecular aminocyanation of alkenes by cooperative palladium/boron
      catalysis.
AB  - A cooperative palladium/triorganoboron catalyst to accomplish the intramolecular
      aminocyanation of alkenes through the cleavage of N-CN bonds is reported. 4,5
      Bis(diphenylphosphino)-9,9-dimethylxanthene (Xantphos) is found to be crucial as
      a ligand for palladium to effectively catalyze the transformation with high chemo
      and regioselectivity. A range of substituted indolines and pyrrolidines with
      both tetra- or trisubstituted carbon and cyano functionalities are readily
      furnished by the newly developed cyanofunctionalization reaction. A preliminary
      example of enantioselective aminocyanation is also described. 

PMID- 24580139
TI  - New insights into bacterial chemoreceptor array structure and assembly from
      electron cryotomography.
AB  - Bacterial chemoreceptors cluster in highly ordered, cooperative, extended arrays
      with a conserved architecture, but the principles that govern array assembly
      remain unclear. Here we show images of cellular arrays as well as selected
      chemoreceptor complexes reconstituted in vitro that reveal new principles of
      array structure and assembly. First, in every case, receptors clustered in a
      trimers-of-dimers configuration, suggesting this is a highly favored fundamental
      building block. Second, these trimers-of-receptor dimers exhibited great
      versatility in the kinds of contacts they formed with each other and with other
      components of the signaling pathway, although only one architectural type
      occurred in native arrays. Third, the membrane, while it likely accelerates the
      formation of arrays, was neither necessary nor sufficient for lattice formation.
      Molecular crowding substituted for the stabilizing effect of the membrane and
      allowed cytoplasmic receptor fragments to form sandwiched lattices that strongly
      resemble the cytoplasmic chemoreceptor arrays found in some bacterial species.
      Finally, the effective determinant of array structure seemed to be CheA and CheW,
      which formed a "superlattice" of alternating CheA-filled and CheA-empty rings
      that linked receptor trimers-of-dimer units into their native hexagonal lattice.
      While concomitant overexpression of receptors, CheA, and CheW yielded arrays with
      native spacing, the CheA occupancy was lower and less ordered, suggesting that
      temporal and spatial coordination of gene expression driven by a single
      transcription factor may be vital for full order, or that array overgrowth may
      trigger a disassembly process. The results described here provide new insights
      into the assembly intermediates and assembly mechanism of this massive
      macromolecular complex.

PMID- 24580142
TI  - Secular trend: morphology and performance.
AB  - In a context of morphological expansion of the general population, how do
      athletes follow such a pattern of anthropometric growth? Is there any relation to
      performance? Biometric data including mass, height, body mass index (BMI) and age
      were collected for 50,376 American athletes representing 249,336 annual
      performers playing in professional baseball, football, ice hockey and basketball.
      Distributions by mass in National Football League (NFL) players are described by
      periods. Field goals have been studied in relation to players' height in the
      National Basketball Association (NBA). Between 1871 and 2011, athletes from the
      four sports have increased significantly in mass, height and BMI, following a
      multi-exponential function series. Consequently, biometric differences between
      athletes and the general population are increasing gradually. Changes in the mass
      distribution within the NFL show the emergence of a biometrical specificity in
      relation to the field position. At the professional level, performance remains
      structured around precise biometric values. In the NBA, a height-attractor at
      201.3 +/- 6.3 cm for the best scorers is invariant, regardless of the level of
      play. These results suggest that laws of growth and biometrics drive high-level
      sport and organise performance around the specific constraint of each field
      position. Discrepancies between some mass and height developments question the
      (disproportionate) large mass increase (relative to the height increase) during
      the 1980s and 1990s. 

PMID- 24580143
TI  - Microporous and mesoporous carbide-derived carbons for strain modification of
      electromechanical actuators.
AB  - Low-voltage stimuli-responsive actuators based on carbide-derived carbon (CDC)
      porous structures were demonstrated. Bending actuators showed a differential
      electromechanical response defined by the porosity of the CDC used in the
      electrode layer. Highly porous CDCs prepared from TiC (mainly microporous), B4C
      (micromesoporous), and Mo2C (mainly mesoporous) precursors were selected to
      demonstrate the influence of porosity parameters on the electromechanical
      performance of actuators. CDC-based bending-type actuators showed a porosity
      driven displacement response over a frequency range of 200 to 0.005 Hz at an
      applied excitation voltage of +/-2 V. The displacement response of the CDC
      actuators increased with an increasing number of mesopores in the electrode
      layer, and the generated strain of the bending actuators was proportional to the
      total porosity (micropores and mesopores) of the CDC. The modifiable
      electromechanical response that arises from the precise porosity control attained
      through tailoring the CDC architecture demonstrates that these actuators hold
      great promise for smart, low-voltage-driven actuation devices. 

PMID- 24580144
TI  - Potential cross-reactivity of monoclonal antibodies against clinically relevant
      mycobacteria.
AB  - Tuberculosis is a disease caused by the Mycobacterium tuberculosis complex (MTb).
      In 2011, global mortality due to tuberculosis was 1.4 million individuals. The
      only available vaccine is the attenuated M. bovis [bacillus Calmette-Guerin
      (BCG)] strain, which confers variable protection against pulmonary tuberculosis.
      Some widely distributed non-tuberculous mycobacteria (NTM), such as M. avium and
      M. arupense, are also potential pathogens for humans. This work aimed to produce
      and characterize monoclonal antibodies against the M. bovis BCG Mexico strain of
      the MTb, M. avium subs. hominissuis and the M. arupense strain from NTM.
      Hybridomas were produced from splenocytes of BALB/c female mice immunized with
      radiation-inactivated mycobacteria, and the immunoglobulin (Ig)G2a antibody
      producing clones with the highest antigenic recognition were selected. The
      selected clones, Mbv 2A10 for M. bovis BCG Mexico, Mav 3H1 for M. avium and Mar
      2D10 for M. arupense, were used in further studies. Enzyme-linked immunosorbent
      assay (ELISA) and immune proteomics analyses characterized the clones as having
      the highest cross-reactivity with mycobacteria. Using mass spectrometry, a number
      of proteins recognized by the monoclonal antibody (mAb) clones were identified.
      These proteins had roles in metabolic processes, hypoxia, cell cycle and
      dormancy. In addition, a Clustal W and Immune Epitope Database (IEDB) in-silico
      analysis was performed in protein sequences that result in the conserved regions
      within probability epitopes that could be recognized for Mbv2A10 and Mav3H1
      clones. 

PMID- 24580146
TI  - Disruption of redox homeostasis and brain damage caused in vivo by methylmalonic
      acid and ammonia in cerebral cortex and striatum of developing rats.
AB  - Hyperammonemia is a common finding in children with methylmalonic acidemia and
      propionic acidemia, but its contribution to the development of the neurological
      symptoms in the affected patients is poorly known. Considering that methylmalonic
      acid (MMA) and propionic acid (PA) predominantly accumulate in these disorders,
      we investigated the effects of hyperammonemia induced by urease treatment in 30
      day-old rats receiving an intracerebroventricular (ICV) injection of MMA or PA on
      important parameters of redox homeostasis in cerebral cortex and striatum. We
      evaluated glutathione (GSH) concentrations, sulfhydryl content, nitrate and
      nitrite concentrations, 2',7'-dichlorofluorescein (DCFH) oxidation, and the
      activity of antioxidant enzymes. MMA decreased GSH concentrations and sulfhydryl
      content and increased nitrate and nitrite concentrations in cerebral cortex and
      striatum from hyperammonemic rats, whereas MMA or ammonia per se did not alter
      these parameters. MMA plus hyperammonemia also decreased glutathione reductase
      activity in rat cerebral cortex, but did not affect catalase, superoxide
      dismutase and glutathione peroxidase activities, neither DCFH oxidation.
      Furthermore, ICV PA administration alone or combined with hyperammonemia did not
      alter any of the evaluated parameters. We also found that pre-treatment with
      antioxidants prevented GSH reduction and sulfhydryl oxidation, whereas N(omega)
      nitro-L-arginine methyl ester (L-NAME) prevented the increased nitrate and
      nitrite concentrations provoked by MMA plus ammonia treatments. Histological
      alterations, including vacuolization, ischemic neurons, and pericellular edema,
      were observed in brain of hyperammonemic rats injected with MMA. The data
      indicate a synergistic effect of MMA and ammonia disturbing redox homeostasis and
      causing morphological brain abnormalities in rat brain.

PMID- 24580147
TI  - Deferasirox for transfusion-dependent patients with myelodysplastic syndromes:
      safety, efficacy, and beyond (GIMEMA MDS0306 Trial).
AB  - BACKGROUND: In the absence of randomized, controlled trial data to support iron
      chelation therapy in transfusion-dependent patients with myelodysplastic
      syndromes (MDS), continued evidence from large prospective clinical trials
      evaluating the efficacy and safety of iron chelation therapy in this patient
      population is warranted. METHODS: The safety and efficacy of deferasirox was
      examined in a prospective, open-label, single-arm, multicenter trial of
      transfusion-dependent patients with International Prognostic Scoring System low-
      or intermediate-1-risk MDS and evidence of transfusion-related iron overload. The
      effects of deferasirox therapy on hematological response and disease progression
      were also examined. RESULTS: Of 159 participants enrolled from 37 Italian
      centers, 152 received >=1 dose of deferasirox (initiated at 10-20 mg/kg/day and
      titrated as appropriate), and 68 completed the study. Of 84 patients who
      discontinued deferasirox therapy, 22 died during the trial, and 28 withdrew due
      to an adverse event (AE). Fourteen treatment-related grade 3 AEs occurred in 11
      patients, whereas no grade 4 or 5 drug-related AEs were reported. Significant
      risks for dropout were a higher serum ferritin level at baseline, a higher MDS
      Specific Comorbidity Index, and a shorter diagnosis-enrollment interval. Median
      serum ferritin level fell from 1966 ng/mL to 1475 ng/mL (P < 0.0001). The
      cumulative incidence of transfusion independence, adjusted for death and disease
      progression, was 2.6%, 12.3%, and 15.5% after 6, 9, and 12 months, respectively.
      CONCLUSIONS: Deferasirox therapy in transfusion-dependent patients with MDS was
      moderately well tolerated and effectively lowered serum ferritin levels. Positive
      hematological responses were observed, and a subset of patients achieved
      transfusion independence.

PMID- 24580151
TI  - Extreme current fluctuations in lattice gases: beyond nonequilibrium steady
      states.
AB  - We use the macroscopic fluctuation theory (MFT) to study large current
      fluctuations in nonstationary diffusive lattice gases. We identify two
      universality classes of these fluctuations, which we call elliptic and
      hyperbolic. They emerge in the limit when the deterministic mass flux is small
      compared to the mass flux due to the shot noise. The two classes are determined
      by the sign of compressibility of effective fluid, obtained by mapping the MFT
      into an inviscid hydrodynamics. An example of the elliptic class is the symmetric
      simple exclusion process, where, for some initial conditions, we can solve the
      effective hydrodynamics exactly. This leads to a super-Gaussian extreme current
      statistics conjectured by Derrida and Gerschenfeld [J. Stat. Phys. 137, 978
      (2009)] and yields the optimal path of the system. For models of the hyperbolic
      class, the deterministic mass flux cannot be neglected, leading to a different
      extreme current statistics.

PMID- 24580148
TI  - Mycophenolic acid, mycophenolate mofetil, mizoribine, ribavirin, and 7
      nitroindole inhibit propagation of Babesia parasites by targeting inosine 5'
      monophosphate dehydrogenase.
AB  - The resistance of Babesia parasites to current anti-babesiosis drugs is an issue
      of major concern. The inosine 5'-monophosphate dehydrogenase (IMPDH) of Babesia
      gibsoni has been identified and characterized as a molecular drug target in our
      previous studies. In the present study, inhibitory effects of IMPDH inhibitors
      (mycophenolate mofetil, mizoribine, ribavirin, 7-nitroindole, and mycophenolic
      acid) were evaluated in vitro or in vivo. In the inhibition assay of recombinant
      B. gibsoni IMPDH activity, mycophenolate mofetil was the most potent inhibitor
      (IC(50) = 2.58 +/- 1.32 MUM) while ribavirin was the least potent. The inhibitory
      effects of mycophenolate mofetil, mizoribine, ribavirin, and 7-nitroindole on the
      in vitro growths of B. gibsoni and Babesia bovis were also assessed. The results
      revealed that mycophenolate mofetil was the most potent inhibitor of the
      multiplications of both B. gibsoni (IC(50) = 0.13 +/- 0.05 MUM) and B. bovis
      (IC(50) = 0.97 +/- 0.49 MUM). Ribavirin was also the least potent for both B.
      gibsoni and B. bovis in vitro. Mycophenolic acid, a metabolite of mycophenolate
      mofetil, caused an inhibition of Babesia microti in mice with noticeable
      improvement in hematological parameters of the infected mice (ED(50) = 44.15 +/-
      12.53 mg/kg). Although the report provides a non-exhaustive view of potential
      treatment strategy without addressing the potential adverse effect of immune
      suppression on infections, these results indicated that the IMPDH might be a
      molecular target of MPA for B. microti . Altogether, we provide a basis for
      development of antibabesia prodrugs by targeting IMPDH of the parasites in the
      treatment of babesiosis.

PMID- 24580152
TI  - Finite-scale singularity in the renormalization group flow of a reaction
      diffusion system.
AB  - We study the nonequilibrium critical behavior of the pair contact process with
      diffusion (PCPD) by means of nonperturbative functional renormalization group
      techniques. We show that usual perturbation theory fails because the effective
      potential develops a nonanalyticity at a finite length scale: Perturbatively
      forbidden terms are dynamically generated and the flow can be continued once they
      are taken into account. Our results suggest that the critical behavior of PCPD
      can be either in the directed percolation or in a different (conjugated)
      universality class. 

PMID- 24580153
TI  - Universal aspects of curved, flat, and stationary-state Kardar-Parisi-Zhang
      statistics.
AB  - Motivated by the recent exact solution of the stationary-state Kardar-Parisi
      Zhang (KPZ) statistics by Imamura and Sasamoto [ Phys. Rev. Lett. 108 190603
      (2012)], as well as a precursor experimental signature unearthed by Takeuchi [
      Phys. Rev. Lett. 110 210604 (2013)], we establish here the universality of these
      phenomena, examining scaling behaviors of directed polymers in a random medium,
      the stochastic heat equation with multiplicative noise, and kinetically roughened
      KPZ growth models. We emphasize the value of cross KPZ-class universalities,
      revealing crossover effects of experimental relevance. Finally, we illustrate the
      great utility of KPZ scaling theory by an optimized numerical analysis of the
      Ulam problem of random permutations.

PMID- 24580154
TI  - Waxing and waning of dynamical heterogeneity in the superionic state.
AB  - Using molecular dynamics simulations of UO2-a type II superionic conductor-we
      identify a well-defined onset of dynamic disorder (Talpha), which is remarkably
      correlated to a nontrivial advance of dynamical heterogeneity (DH). Quantified by
      the correlations in the dynamic propensity and van Hove self-correlation
      function, the DH is shown to grow with increasing temperature from Talpha, peak
      at an intermediate temperature between Talpha and Tlambda-the superionic
      transition temperature-and then recede. Surprisingly, the DH attributes are not
      uniform across the temperatures-our investigation shows a low temperature
      (alphaT) stage DH, which is characterized by weak correlations and a plateaulike
      period in the correlations of the propensity, and a high temperature (lambdaT)
      stage DH with strong correlations that are analogous to those in typical
      supercooled liquids. Our work, which has rigorously identified the onset of
      superionicity, gives a different direction for interpreting scattering
      experiments on the basis of statistical, correlated dynamics. 

PMID- 24580155
TI  - Controlling active self-assembly through broken particle-shape symmetry.
AB  - Many structural properties of conventional passive materials are known to arise
      from the symmetries of their microscopic constituents. By contrast, it is largely
      unclear how the interplay between particle shape and self-propulsion controls the
      meso- and macroscale behavior of active matter. Here we use large-scale
      simulations of homo- and heterogeneous self-propelled particle systems to
      identify generic effects of broken particle-shape symmetry on collective motion.
      We find that even small violations of fore-aft symmetry lead to fundamentally
      different collective behaviors, which may facilitate demixing of differently
      shaped species as well as the spontaneous formation of stable microrotors. These
      results suggest that variation of particle shape yields robust physical
      mechanisms to control self-assembly of active matter, with possibly profound
      implications for biology and materials design. 

PMID- 24580156
TI  - Circular Kardar-Parisi-Zhang equation as an inflating, self-avoiding ring
      polymer.
AB  - We consider the Kardar-Parisi-Zhang equation for a circular interface in two
      dimensions, unconstrained by the standard small-slope and no-overhang
      approximations. Numerical simulations using an adaptive scheme allow us to
      elucidate the complete time evolution as a crossover between a short-time regime
      with the interface fluctuations of a self-avoiding ring or two-dimensional
      vesicle, and a long-time regime governed by the Tracy-Widom distribution expected
      for this geometry. For small-noise amplitudes, scaling behavior is only of the
      latter type. Large noise is also seen to renormalize the bare physical parameters
      of the ring, akin to analogous parameter renormalization for equilibrium three
      dimensional membranes. Our results bear particular importance on the relation
      between relevant universality classes of scale-invariant systems in two
      dimensions. 

PMID- 24580157
TI  - Magnetic-field-induced suppression of the amorphous blue phase.
AB  - We present magneto-optical measurements on two liquid crystals that exhibit a
      wide temperature-range amorphous blue phase (BPIII). Magnetic fields up to 25 T
      are found to suppress the onset of BPIII in both materials by almost 1  degrees
      C. This effect appears to increase nonlinearly with the field strength. The
      effect of high fields on established BPIIIs is also reported, in which we find
      significant hysteresis and very slow dynamics. Possible explanations of these
      results are discussed. 

PMID- 24580158
TI  - Bifurcation in epigenetics: implications in development, proliferation, and
      diseases.
AB  - Cells often exhibit different and stable phenotypes from the same DNA sequence.
      Robustness and plasticity of such cellular states are controlled by diverse
      transcriptional and epigenetic mechanisms, among them the modification of
      biochemical marks on chromatin. Here, we develop a stochastic model that
      describes the dynamics of epigenetic marks along a given DNA region. Through
      mathematical analysis, we show the emergence of bistable and persistent
      epigenetic states from the cooperative recruitment of modifying enzymes. We also
      find that the dynamical system exhibits a critical point and displays, in the
      presence of asymmetries in recruitment, a bifurcation diagram with hysteresis.
      These results have deep implications for our understanding of epigenetic
      regulation. In particular, our study allows one to reconcile within the same
      formalism the robust maintenance of epigenetic identity observed in
      differentiated cells, the epigenetic plasticity of pluripotent cells during
      differentiation, and the effects of epigenetic misregulation in diseases.
      Moreover, it suggests a possible mechanism for developmental transitions where
      the system is shifted close to the critical point to benefit from high
      susceptibility to developmental cues. 

PMID- 24580159
TI  - From the Kuramoto-Sakaguchi model to the Kuramoto-Sivashinsky equation.
AB  - We derive the Kuramoto-Sivashinsky-type phase equation from the Kuramoto
      Sakaguchi-type phase model via the Ott-Antonsen-type complex amplitude equation
      and demonstrate heterogeneity-induced collective-phase turbulence in nonlocally
      coupled individual-phase oscillators. 

PMID- 24580161
TI  - Flow-induced structures versus flow instabilities.
AB  - The Taylor-Couette flow of a dilute micellar system known to generate shear
      induced structures is investigated through simultaneous rheometry and ultrasonic
      imaging. We show that flow instabilities must be taken into account since both
      Reynolds and Weissenberg numbers may be large. Before nucleation of shear-induced
      structures, the flow can be inertially unstable, but once shear-induced
      structures are nucleated, the kinematics of the flow become chaotic, in a pattern
      reminiscent of the elastically dominated turbulence known in dilute polymer
      solutions. We outline a general framework for the interplay between flow
      instabilities and flow-induced structures. 

PMID- 24580160
TI  - Effect of solvents on the pattern formation in a Belousov-Zhabotinsky reaction
      embedded into a microemulsion.
AB  - Using the ferroin- and the bathoferroin-catalyzed Belousov-Zhabotinsky (BZ)
      reaction embedded in the sodium-bis (2-ethylhexyl) sulfosuccinate (AOT) water-in
      oil microemulsion, we observed different patterns occurring in two different
      solvents, hexane and octane. Turing patterns were found in both solvents with
      ferroin. They differ in their interaction with coexisting bulk oscillations, such
      that a new excitation front was formed around the evolving Turing patterns in
      hexane. However, in octane, the bulk oscillation merged with the evolving
      patterns, forming a new excitation front, which propagated into two directions:
      towards the existing patterns and away from them. For the bathoferroin-catalyzed
      BZ reaction, patterns like dash waves, jumping waves, and bubble waves were found
      in both solvents having different wavelengths. A curvature dependence of the
      splitting and merging of dashes was found. 

PMID- 24580162
TI  - Gray solitons on the surface of water.
AB  - The dynamics of surface gravity water waves can be described by the self
      defocusing nonlinear Schrodinger equation. Recent observations of black solitons
      on the surface of water confirmed its validity for finite, below critical depth.
      The black soliton is a limiting case of a family of gray soliton solutions with
      finite amplitude depressions. Here, we report observations of gray solitons in
      water waves, thus, complementing our previous observations of black solitons. 

PMID- 24580163
TI  - Spinning Janus doublets driven in uniform ac electric fields.
AB  - We provide an experimental proof of concept for a robust, continuously rotating
      microstructure-consisting of two metallodielectric (gold-polystyrene) Janus
      particles rigidly attached to each other-which is driven in uniform ac fields by
      asymmetric induced-charge electro-osmosis. The pairs (doublets) are stabilized on
      the substrate surface which is parallel to the plane of view and normal to the
      direction of the applied electric field. We find that the radius of orbit and
      angular velocity of the pair are predominantly dependent on the relative
      orientations of the interfaces between the metallic and dielectric hemispheres
      and that the electrohydrodynamic particle-particle interactions are small.
      Additionally, we verify that both the angular and linear velocities of the pair
      are proportional to the square of the applied field which is consistent with the
      theory for nonlinear electrokinetics. A simple kinematic rigid body model is used
      to predict the paths and doublet velocities (angular and linear) based on their
      relative orientations with good agreement. 

PMID- 24580164
TI  - Dark- and bright-rogue-wave solutions for media with long-wave-short-wave
      resonance.
AB  - Exact explicit rogue-wave solutions of intricate structures are presented for the
      long-wave-short-wave resonance equation. These vector parametric solutions
      feature coupled dark- and bright-field counterparts of the Peregrine soliton.
      Numerical simulations show the robustness of dark and bright rogue waves in spite
      of the onset of modulational instability. Dark fields originate from the complex
      interplay between anomalous dispersion and the nonlinearity driven by the coupled
      long wave. This unusual mechanism, not available in scalar nonlinear wave
      equation models, can provide a route to the experimental realization of dark
      rogue waves in, for instance, negative index media or with capillary-gravity
      waves. 

PMID- 24580165
TI  - Self-assembly of magnetic balls: from chains to tubes.
AB  - The self-assembly of spherical magnets (magnetic balls) is addressed
      theoretically. Minimal energy structures are obtained by optimization procedures
      as well as Monte Carlo computer simulations. Three typical shapes are obtained
      depending on the number of constitutive magnets N. In the regime of small N,
      chains are stable as dimers or trimers (i.e., N<=3), then rings become stable for
      (4<=N<=13) where dipole vectors adopt a vortexlike arrangement. A major finding
      concerns the stacking of rings as soon as N is large enough (N>=14). The number
      of stacked rings is found to increase as N^{2/3}, leading to a tubular structure
      at large N. All the relevant predicted shapes are experimentally reproduced by
      manipulating millimetric magnets. 

PMID- 24580166
TI  - Energy flow in periodic thermodynamics.
AB  - A key quantity characterizing a time-periodically forced quantum system coupled
      to a heat bath is the energy flowing in the steady state through the system into
      the bath, where it is dissipated. We derive a general expression which allows one
      to compute this energy dissipation rate for a heat bath consisting of a large
      number of harmonic oscillators and work out two analytically solvable model
      examples. In particular, we distinguish between genuine transitions effectuating
      a change of the systems's Floquet state and pseudotransitions preserving that
      state; the latter are shown to yield an important contribution to the total
      dissipation rate. Our results suggest possible driving-mediated heating and
      cooling schemes on the quantum level. They also indicate that a driven system
      does not necessarily occupy only a single Floquet state when in contact with a
      zero-temperature bath. 

PMID- 24580167
TI  - Dynamics and termination cost of spatially coupled mean-field models.
AB  - This work is motivated by recent progress in information theory and signal
      processing where the so-called spatially coupled design of systems leads to
      considerably better performance. We address relevant open questions about
      spatially coupled systems through the study of a simple Ising model. In
      particular, we consider a chain of Curie-Weiss models that are coupled by
      interactions up to a certain range. Indeed, it is well known that the pure
      (uncoupled) Curie-Weiss model undergoes a first-order phase transition driven by
      the magnetic field, and furthermore in the spinodal region such systems are
      unable to reach equilibrium in subexponential time if initialized in the
      metastable state. In contrast, the spatially coupled system is instead able to
      reach the equilibrium even when initialized to the metastable state. The
      equilibrium phase propagates along the chain in the form of a traveling wave.
      Here we study the speed of the wave front and the so-called termination cost
      i.e., the conditions necessary for the propagation to occur. We reach several
      interesting conclusions about optimization of the speed and the cost. 

PMID- 24580168
TI  - Thermal properties of a particle confined to a parabolic quantum well in two
      dimensional space with conical disclination.
AB  - The thermal properties of a system, comprising of a spinless noninteracting
      charged particle in the presence of a constant external magnetic field and
      confined in a parabolic quantum well are studied. The focus has been on the
      effects of a topological defect, of the form of conical disclination, with regard
      to the thermodynamic properties of the system. We have obtained the modifications
      to the traditional Landau-Fock-Darwin spectrum in the presence of conical
      disclination. The effect of the conical kink on the degeneracy structure of the
      energy levels is investigated. The canonical formalism is used to compute various
      thermodynamic variables. The study shows an interplay between magnetic field,
      temperature, and the degree of conicity by setting two scales for temperature
      corresponding to the frequency of the confining potential and the cyclotron
      frequency of external magnetic field. The kink parameter is found to affect the
      quantitative behavior of the thermodynamic quantities. It plays a crucial role in
      the competition between the external magnetic field and temperature in fixing the
      values of the thermal response functions. This study provides an important
      motivation for studying similar systems, however with nontrivial interactions in
      the presence of topological defects. 

PMID- 24580169
TI  - Superlinear scaling of offspring at criticality in branching processes.
AB  - For any branching process, we demonstrate that the typical total number
      rmp(nutau) of events triggered over all generations within any sufficiently large
      time window tau exhibits, at criticality, a superlinear dependence
      rmp(nutau)~(nutau)gamma (with gamma>1) on the total number nutau of the
      immigrants arriving at the Poisson rate nu. In branching processes in which
      immigrants (or sources) are characterized by fertilities distributed according to
      an asymptotic power-law tail with tail exponent 1<gamma?2, the exponent of the
      superlinear law for rmp(nutau) is identical to the exponent gamma of the
      distribution of fertilities. For gamma>2 and for standard branching processes
      without power-law distribution of fertilities, rmp(nutau)~(nutau)2. This scaling
      law replaces and tames the divergence nutau/(1-n) of the mean total number
      Rt(tau) of events, as the branching ratio (defined as the average number of
      triggered events of first generation per source) tends to 1. The derivation uses
      the formalism of generating probability functions. The corresponding prediction
      is confirmed by numerical calculations, and an heuristic derivation enlightens
      its underlying mechanism. We also show that Rt(tau) is always linear in nutau
      even at criticality (n=1). Our results thus illustrate the fundamental difference
      between the mean total number, which is controlled by a few extremely rare
      realizations, and the typical behavior represented by rmp(nutau).

PMID- 24580170
TI  - Finite size induces crossover temperature in growing spin chains.
AB  - We introduce a growing one-dimensional quenched spin model that bases on
      asymmetrical one-side Ising interactions in the presence of external field.
      Numerical simulations and analytical calculations based on Markov chain theory
      show that when the external field is smaller than the exchange coupling constant
      J there is a nonmonotonous dependence of the mean magnetization on the
      temperature in a finite system. The crossover temperature Tc corresponding to the
      maximal magnetization decays with system size, approximately as the inverse of
      the Lambert W function. The observed phenomenon can be understood as an interplay
      between the thermal fluctuations and the presence of the first cluster determined
      by initial conditions. The effect exists also when spins are not quenched but
      fully thermalized after the attachment to the chain. By performing tests on real
      data we conceive the model is in part suitable for a qualitative description of
      online emotional discussions arranged in a chronological order, where a spin in
      every node conveys emotional valence of a subsequent post. 

PMID- 24580171
TI  - Simultaneously selecting appropriate partners for gaming and strategy adaptation
      to enhance network reciprocity in the prisoner's dilemma.
AB  - Network reciprocity is one mechanism for adding social viscosity, which leads to
      cooperative equilibrium in 2 * 2 prisoner's dilemma games. Previous studies have
      shown that cooperation can be enhanced by using a skewed, rather than a random,
      selection of partners for either strategy adaptation or the gaming process. Here
      we show that combining both processes for selecting a gaming partner and an
      adaptation partner further enhances cooperation, provided that an appropriate
      selection rule and parameters are adopted. We also show that this combined model
      significantly enhances cooperation by reducing the degree of activity in the
      underlying network; we measure the degree of activity with a quantity called
      effective degree. More precisely, during the initial evolutionary stage in which
      the global cooperation fraction declines because initially allocated cooperators
      becoming defectors, the model shows that weak cooperative clusters perish and
      only a few strong cooperative clusters survive. This finding is the most
      important key to attaining significant network reciprocity. 

PMID- 24580172
TI  - Nonlinear degradation-enhanced transport of morphogens performing subdiffusion.
AB  - We study a morphogen gradient formation under nonlinear degradation and
      subdiffusive transport. In the long-time limit, we obtain the nonlinear effect of
      degradation-enhanced diffusion, resulting from the interaction of non-Markovian
      subdiffusive transport with a nonlinear reaction. We find the stationary profile
      of power-law type, which has implications for robustness, with the shape of the
      profile being controlled by the anomalous exponent. Far away from the source of
      morphogens, any changes in the rate of production are not felt. 

PMID- 24580173
TI  - Thermodynamic induction effects exhibited in nonequilibrium systems with variable
      kinetic coefficients.
AB  - A nonequilibrium thermodynamic theory demonstrating an induction effect of a
      statistical nature is presented. We have shown that this thermodynamic induction
      can arise in a class of systems that have variable kinetic coefficients (VKC). In
      particular if a kinetic coefficient associated with a given thermodynamic
      variable depends on another thermodynamic variable then we have derived an
      expression that can predict the extent of the induction. The amount of induction
      is shown to be proportional to the square of the driving force. The nature of the
      intervariable coupling for the induction effect has similarities with the Onsager
      symmetry relations, though there is an important sign difference as well as the
      magnitudes not being equal. Thermodynamic induction adds nonlinear terms that
      improve the stability of stationary states, at least within the VKC class of
      systems. Induction also produces a term in the expression for the rate of entropy
      production that could be interpreted as self-organization. Many of these results
      are also obtained using a variational approach, based on maximizing entropy
      production, in a certain sense. Nonequilibrium quantities analogous to the free
      energies of equilibrium thermodynamics are introduced. 

PMID- 24580174
TI  - Social dilemma alleviated by sharing the gains with immediate neighbors.
AB  - We study the evolution of cooperation in the evolutionary spatial prisoner's
      dilemma game (PDG) and snowdrift game (SG), within which a fraction alpha of the
      payoffs of each player gained from direct game interactions is shared equally by
      the immediate neighbors. The magnitude of the parameter alpha therefore
      characterizes the degree of the relatedness among the neighboring players. By
      means of extensive Monte Carlo simulations as well as an extended mean-field
      approximation method, we trace the frequency of cooperation in the stationary
      state. We find that plugging into relatedness can significantly promote the
      evolution of cooperation in the context of both studied games. Unexpectedly,
      cooperation can be more readily established in the spatial PDG than that in the
      spatial SG, given that the degree of relatedness and the cost-to-benefit ratio of
      mutual cooperation are properly formulated. The relevance of our model with the
      stakeholder theory is also briefly discussed. 

PMID- 24580175
TI  - Model of waterlike fluid under confinement for hydrophobic and hydrophilic
      particle-plate interaction potentials.
AB  - Molecular dynamic simulations were employed to study a waterlike model confined
      between hydrophobic and hydrophilic plates. The phase behavior of this system is
      obtained for different distances between the plates and particle-plate
      potentials. For both hydrophobic and hydrophilic walls, there are the formation
      of layers. Crystallization occurs at lower temperature at the contact layer than
      at the middle layer. In addition, the melting temperature decreases as the plates
      become more hydrophobic. Similarly, the temperatures of maximum density and
      extremum diffusivity decrease with hydrophobicity. 

PMID- 24580176
TI  - Rank distributions: a panoramic macroscopic outlook.
AB  - This paper presents a panoramic macroscopic outlook of rank distributions. We
      establish a general framework for the analysis of rank distributions, which
      classifies them into five macroscopic "socioeconomic" states: monarchy, oligarchy
      feudalism, criticality, socialism-capitalism, and communism. Oligarchy-feudalism
      is shown to be characterized by discrete macroscopic rank distributions, and
      socialism-capitalism is shown to be characterized by continuous macroscopic size
      distributions. Criticality is a transition state between oligarchy-feudalism and
      socialism-capitalism, which can manifest allometric scaling with multifractal
      spectra. Monarchy and communism are extreme forms of oligarchy-feudalism and
      socialism-capitalism, respectively, in which the intrinsic randomness vanishes.
      The general framework is applied to three different models of rank distributions
      top-down, bottom-up, and global-and unveils each model's macroscopic universality
      and versatility. The global model yields a macroscopic classification of the
      generalized Zipf law, an omnipresent form of rank distributions observed across
      the sciences. An amalgamation of the three models establishes a universal rank
      distribution explanation for the macroscopic emergence of a prevalent class of
      continuous size distributions, ones governed by unimodal densities with both
      Pareto and inverse-Pareto power-law tails. 

PMID- 24580177
TI  - Contact process on generalized Fibonacci chains: infinite-modulation criticality
      and double-log periodic oscillations.
AB  - We study the nonequilibrium phase transition of the contact process with
      aperiodic transition rates using a real-space renormalization group as well as
      Monte Carlo simulations. The transition rates are modulated according to the
      generalized Fibonacci sequences defined by the inflation rules A -> ABk and B ->
      A. For k=1 and 2, the aperiodic fluctuations are irrelevant, and the
      nonequilibrium transition is in the clean directed percolation universality
      class. For k>=3, the aperiodic fluctuations are relevant. We develop a complete
      theory of the resulting unconventional "infinite-modulation" critical point,
      which is characterized by activated dynamical scaling. Moreover, observables such
      as the survival probability and the size of the active cloud display pronounced
      double-log periodic oscillations in time which reflect the discrete scale
      invariance of the aperiodic chains. We illustrate our theory by extensive
      numerical results, and we discuss relations to phase transitions in other
      quasiperiodic systems. 

PMID- 24580178
TI  - Breakdown of fast water transport in graphene oxides.
AB  - Fast slip flow was identified for water inside the interlayer gallery between
      graphene layers or carbon nanotubes. We report here that this significant flow
      rate enhancement (over two orders) breaks down with the presence of chemical
      functionalization and relaxation of nanoconfinement in graphene oxides. Molecular
      dynamics simulation results show that hydrodynamics applies in this circumstance,
      even at length scales down to nanometers. However, corrections to the slip
      boundary condition and apparent viscosity of nanoconfined flow must be included
      to make quantitative predictions. These results were discussed with the
      structural characteristics of liquid water and hydrogen-bond networks. 

PMID- 24580179
TI  - Generalized entropy production phenomena: a master-equation approach.
AB  - The time rate of generalized entropic forms, defined in terms of discrete
      probabilities following a master equation, is investigated. Both contributions,
      namely entropy production and flux, are obtained, extending works carried
      previously for the Boltzmann-Gibbs entropy to a wide class of entropic forms.
      Particularly, it is shown that the entropy-production contribution is always non
      negative for such entropies. Some illustrative examples for known generalized
      entropic forms in the literature are also worked out. Since generalized entropies
      have been lately associated with several complex systems in nature, the present
      analysis should be applicable to irreversible processes in these systems. 

PMID- 24580180
TI  - Scaled Brownian motion as a mean-field model for continuous-time random walks.
AB  - We consider scaled Brownian motion (sBm), a random process described by a
      diffusion equation with explicitly time-dependent diffusion coefficient
      D(t)=alphaD0talpha-1 (Batchelor's equation) which, for alpha<1, is often used for
      fitting experimental data for subdiffusion of unclear genesis. We show that this
      process is a close relative of subdiffusive continuous-time random walks and
      describes the motion of the rescaled mean position of a cloud of independent
      walkers. It shares with subdiffusive continuous-time random walks its
      nonstationary and nonergodic properties. The nonergodicity of sBm does not
      however go hand in hand with strong difference between its different
      realizations: its heterogeneity ("ergodicity breaking") parameter tends to zero
      for long trajectories.

PMID- 24580181
TI  - Percolation of spatially constrained Erdos-Renyi networks with degree
      correlations.
AB  - Motivated by experiments on activity in neuronal cultures [ J. Soriano, M.
      Rodriguez Martinez, T. Tlusty and E. Moses Proc. Natl. Acad. Sci. 105 13758
      (2008)], we investigate the percolation transition and critical exponents of
      spatially embedded Erdos-Renyi networks with degree correlations. In our model
      networks, nodes are randomly distributed in a two-dimensional spatial domain, and
      the connection probability depends on Euclidian link length by a power law as
      well as on the degrees of linked nodes. Generally, spatial constraints lead to
      higher percolation thresholds in the sense that more links are needed to achieve
      global connectivity. However, degree correlations favor or do not favor
      percolation depending on the connectivity rules. We employ two construction
      methods to introduce degree correlations. In the first one, nodes stay
      homogeneously distributed and are connected via a distance- and degree-dependent
      probability. We observe that assortativity in the resulting network leads to a
      decrease of the percolation threshold. In the second construction methods, nodes
      are first spatially segregated depending on their degree and afterwards connected
      with a distance-dependent probability. In this segregated model, we find a
      threshold increase that accompanies the rising assortativity. Additionally, when
      the network is constructed in a disassortative way, we observe that this property
      has little effect on the percolation transition. 

PMID- 24580182
TI  - Structure-function hierarchies and von Karman-Howarth relations for turbulence in
      magnetohydrodynamical equations.
AB  - We generalize the method of A. M. Polyakov, [ Phys. Rev. E 52 6183 (1995)] for
      obtaining structure-function relations in turbulence in the stochastically forced
      Burgers equation, to develop structure-function hierarchies for turbulence in
      three models for magnetohydrodynamics (MHD). These are the Burgers analogs of MHD
      in one dimension [ Eur. Phys. J. B 9 725 (1999)], and in three dimensions (3DMHD
      and 3D Hall MHD). Our study provides a convenient and unified scheme for the
      development of structure-function hierarchies for turbulence in a variety of
      coupled hydrodynamical equations. For turbulence in the three sets of MHD
      equations mentioned above, we obtain exact relations for third-order structure
      functions and their derivatives; these expressions are the analogs of the von
      Karman-Howarth relations for fluid turbulence. We compare our work with earlier
      studies of such relations in 3DMHD and 3D Hall MHD. 

PMID- 24580183
TI  - Analysis of spanning avalanches in the two-dimensional nonequilibrium zero
      temperature random-field Ising model.
AB  - We present a numerical analysis of spanning avalanches in a two-dimensional (2D)
      nonequilibrium zero-temperature random field Ising model. Finite-size scaling
      analysis, performed for distribution of the average number of spanning avalanches
      per single run, spanning avalanche size distribution, average size of spanning
      avalanche, and contribution of spanning avalanches to magnetization jump, is
      augmented by analysis of spanning field (i.e., field triggering spanning
      avalanche), which enabled us to collapse averaged magnetization curves below
      critical disorder. Our study, based on extensive simulations of sufficiently
      large systems, reveals the dominant role of subcritical 2D-spanning avalanches in
      model behavior below and at the critical disorder. Other types of avalanches
      influence finite systems, but their contribution for large systems remains small
      or vanish. 

PMID- 24580184
TI  - Frequency response of a thermal diode.
AB  - A thermal diode that rectifies heat current is one of the basic devices for
      functional heat control. Frequency response is an important feature of many
      electric devices, such as diodes and transistors. Frequency response measures the
      ability of a device to process high-frequency signals. In this paper, we
      systematically study the frequency response of a thermal diode model that
      consists of two dissimilar Frenkel-Kontorova (FK) segments. The rectification
      ability of this thermal diode is badly affected when the input temperatures
      oscillate with a frequency that exceeds a critical value. The dependence of this
      critical frequency on various system parameters, including system size, interface
      coupling strength, etc., is quantitatively calculated. 

PMID- 24580185
TI  - Geometric structure of percolation clusters.
AB  - We investigate the geometric properties of percolation clusters by studying
      square-lattice bond percolation on the torus. We show that the density of bridges
      and nonbridges both tend to 1/4 for large system sizes. Using Monte Carlo
      simulations, we study the probability that a given edge is not a bridge but has
      both its loop arcs in the same loop and find that it is governed by the two-arm
      exponent. We then classify bridges into two types: branches and junctions. A
      bridge is a branch iff at least one of the two clusters produced by its deletion
      is a tree. Starting from a percolation configuration and deleting the branches
      results in a leaf-free configuration, whereas, deleting all bridges produces a
      bridge-free configuration. Although branches account for ~43% of all occupied
      bonds, we find that the fractal dimensions of the cluster size and hull length of
      leaf-free configurations are consistent with those for standard percolation
      configurations. By contrast, we find that the fractal dimensions of the cluster
      size and hull length of bridge-free configurations are given by the backbone and
      external perimeter dimensions, respectively. We estimate the backbone fractal
      dimension to be 1.643 36(10). 

PMID- 24580186
TI  - Melting behavior and different bound states in three-stranded DNA models.
AB  - Thermal denaturation of DNA is often studied with coarse-grained models in which
      native sequential base pairing is mimicked by the existence of attractive
      interactions only between monomers at the same position along strands (Poland and
      Scheraga models). Within this framework, the existence of a three-stranded DNA
      bound state in conditions where a duplex DNA would be in the denaturated state
      was recently predicted from a study of three directed polymer models on
      simplified hierarchical lattices (d>2) and in 1+1 dimensions. Such a phenomenon
      which is similar to the Efimov effect in nuclear physics was named Efimov-DNA. In
      this paper we study the melting of the three-stranded DNA on a Sierpinski gasket
      of dimensions d<2 by assigning extra weight factors to fork openings and
      closings, to induce a two-strand DNA melting. In such a context we can find again
      the existence of the Efimov-DNA-like state but quite surprisingly we discover
      also the presence of a different phase, to be called a mixed state, where the
      strands are pair-wise bound but without three chain contacts. Whereas the Efimov
      DNA turns out to be a crossover near melting, the mixed phase is a thermodynamic
      phase. 

PMID- 24580187
TI  - Radial propagation in population dynamics with density-dependent diffusion.
AB  - Population dynamics that evolve in a radial symmetric geometry are investigated.
      The nonlinear reaction-diffusion model, which depends on population density, is
      employed as the governing equation for this system. The approximate analytical
      solution to this equation is found. It shows that the population density evolves
      from the initial state and propagates in a traveling-wave-like manner for a long
      time scale. If the distance is insufficiently long, the curvature has an
      ineluctable influence on the density profile and front speed. In comparison, the
      analytical solution is in agreement with the numerical solution. 

PMID- 24580188
TI  - Efficiency and dissipation in a two-terminal thermoelectric junction, emphasizing
      small dissipation.
AB  - The efficiency and cooling power of a two-terminal thermoelectric refrigerator
      are analyzed near the limit of vanishing dissipation (ideal system), where the
      optimal efficiency is the Carnot one, but the cooling power vanishes. This limit,
      where transport occurs only via a single sharp electronic energy, has been
      referred to as "strong coupling" or "the best thermoelectric." Confining the
      discussion to the linear-response regime, it is found that "parasitic" effects
      that make the system deviate from the ideal limit, and reduce the efficiency from
      the Carnot limit, are crucial for the usefulness of the device. Among these
      parasitics, there are: parallel phonon conduction, finite width of the electrons'
      transport band, and more than a single energy transport channel. In terms of a
      small parameter characterizing the deviation from the ideal limit, the efficiency
      and power grow linearly, and the dissipation quadratically. The results are
      generalized to the case of broken time-reversal symmetry, and the major
      nontrivial changes are discussed. Finally, the recent universal relation between
      the thermopower and the asymmetry of the dissipation between the two terminals is
      briefly discussed, including the small dissipation limit. 

PMID- 24580189
TI  - Truncated phase-space approach to polaron response.
AB  - A method is presented to obtain the linear response coefficients of a system
      coupled to a bath. The method is based on a systematic truncation of the
      Liouville equation for the reduced distribution function. The first-order
      truncation results are expected to be accurate in the low-temperature and weak
      coupling regime. Explicit expressions for the conductivity of the Frohlich
      polaron are obtained, and the discrepancy between the Kadanoff and the Feynman
      Hellwarth-Iddings-Platzman mobility is elucidated. 

PMID- 24580190
TI  - Entanglement in ground and excited states of gapped free-fermion systems and
      their relationship with Fermi surface and thermodynamic equilibrium properties.
AB  - We study bipartite entanglement entropies in the ground and excited states of
      free-fermion models, where a staggered potential, MUs, induces a gap in the
      spectrum. Ground-state entanglement entropies satisfy the "area law", and the
      "area-law" coefficient is found to diverge as a logarithm of the staggered
      potential, when the system has an extended Fermi surface at MUs=0. On the square
      lattice, we show that the coefficient of the logarithmic divergence depends on
      the Fermi surface geometry and its orientation with respect to the real-space
      interface between subsystems and is related to the Widom conjecture as enunciated
      by Gioev and Klich [ Phys. Rev. Lett. 96 100503 (2006)]. For point Fermi surfaces
      in two-dimension, the "area-law" coefficient stays finite as MUs->0. The von
      Neumann entanglement entropy associated with the excited states follows a "volume
      law" and allows us to calculate an entropy density function sV(e), which is
      substantially different from the thermodynamic entropy density function sT(e),
      when the lattice is bipartitioned into two equal subsystems but approaches the
      thermodynamic entropy density as the fraction of sites in the larger subsystem,
      that is integrated out, approaches unity. 

PMID- 24580191
TI  - Kosterlitz-Thouless and Potts transitions in a generalized XY model.
AB  - We present extensive numerical simulations of a generalized XY model with nematic
      like terms recently proposed by Poderoso et al. [ Phys. Rev. Lett. 106 067202
      (2011)]. Using finite size scaling and focusing on the q=3 case, we locate the
      transitions between the paramagnetic (P), the nematic-like (N), and the
      ferromagnetic (F) phases. The results are compared with the recently derived
      lower bounds for the P-N and P-F transitions. While the P-N transition is found
      to be very close to the lower bound, the P-F transition occurs significantly
      above the bound. Finally, the transition between the nematic-like and the
      ferromagnetic phases is found to belong to the three-states Potts universality
      class. 

PMID- 24580192
TI  - Jarzynski equality for quantum stochastic maps.
AB  - Jarzynski equality and related fluctuation theorems can be formulated for various
      setups. Such an equality was recently derived for nonunitary quantum evolutions
      described by unital quantum operations, i.e., for completely positive, trace
      preserving maps, which preserve the maximally mixed state. We analyze here a more
      general case of arbitrary quantum operations on finite systems and derive the
      corresponding form of the Jarzynski equality. It contains a correction term due
      to nonunitality of the quantum map. Bounds for the relative size of this
      correction term are established and they are applied for exemplary systems
      subjected to quantum channels acting on a finite-dimensional Hilbert space. 

PMID- 24580193
TI  - Effects of geometrical frustration on the spin-glass transition.
AB  - Randomness and frustration are important for the spin-glass transitions. Ising
      antiferromagnet on a stacked triangular lattice is a highly frustrated system.
      Phase diagram is obtained within a cluster approximation for the system with
      randomness in the interaction between Ising spins. To see the frustration
      effects, the phase diagram of the antiferromagnet is compared with the
      corresponding one of the ferromagnet. Spin-glass phase of the antiferromagnet
      appears much more easily by the randomness than that of the ferromagnet. 

PMID- 24580194
TI  - Weighted reciprocal of temperature, weighted thermal flux, and their applications
      in finite-time thermodynamics.
AB  - The concepts of weighted reciprocal of temperature and weighted thermal flux are
      proposed for a heat engine operating between two heat baths and outputting
      mechanical work. With the aid of these two concepts, the generalized
      thermodynamic fluxes and forces can be expressed in a consistent way within the
      framework of irreversible thermodynamics. Then the efficiency at maximum power
      output for a heat engine, one of key topics in finite-time thermodynamics, is
      investigated on the basis of a generic model under the tight-coupling condition.
      The corresponding results have the same forms as those of low-dissipation heat
      engines [ M. Esposito, R. Kawai, K. Lindenberg and C. Van den Broeck Phys. Rev.
      Lett. 105 150603 (2010)]. The mappings from two kinds of typical heat engines,
      such as the low-dissipation heat engine and the Feynman ratchet, into the present
      generic model are constructed. The universal efficiency at maximum power output
      up to the quadratic order is found to be valid for a heat engine coupled
      symmetrically and tightly with two baths. The concepts of weighted reciprocal of
      temperature and weighted thermal flux are also transplanted to the optimization
      of refrigerators. 

PMID- 24580195
TI  - Analytical solution of the generalized Langevin equation with hydrodynamic
      interactions: subdiffusion of heavy tracers.
AB  - We consider a generalized Langevin equation that can be used to describe thermal
      motion of a tracer in a viscoelastic medium by accounting for inertial and
      hydrodynamic effects at short times, subdiffusive scaling at intermediate times,
      and eventual optical trapping at long times. We derive a Laplace-type integral
      representation for the linear response function that governs the diffusive
      dynamics. This representation is particularly well suited for rapid numerical
      computation and theoretical analysis. In particular, we deduce explicit formulas
      for the mean and variance of the time averaged (TA) mean square displacement
      (MSD) and velocity autocorrelation function (VACF). The asymptotic behavior of
      the TA MSD and TA VACF is investigated at different time scales. Some biophysical
      and microrheological applications are discussed, with an emphasis on the
      statistical analysis of optical tweezers' single-particle tracking experiments in
      polymer networks and living cells. 

PMID- 24580196
TI  - Macroscopically deterministic Markovian thermalization in finite quantum spin
      systems.
AB  - A key feature of nonequilibrium thermodynamics is the Markovian, deterministic
      relaxation of coarse observables such as, for example, the temperature difference
      between two macroscopic objects which evolves independently of almost all details
      of the initial state. We demonstrate that the unitary dynamics for moderately
      sized spin-1/2 systems may yield the same type of relaxation dynamics for a given
      magnetization difference. This observation might contribute to the understanding
      of the emergence of thermodynamics within closed quantum systems. 

PMID- 24580197
TI  - Numerical comparison of a constrained path ensemble and a driven quasisteady
      state.
AB  - We investigate the correspondence between a nonequilibrium ensemble defined via
      the distribution of phase-space paths of a Hamiltonian system and a system driven
      into a steady state by nonequilibrium boundary conditions. To discover whether
      the nonequilibrium path ensemble adequately describes the physics of a driven
      system, we measure transition rates in a simple one-dimensional model of rotors
      with Newtonian dynamics and purely conservative interactions. We compare those
      rates with known properties of the nonequilibrium path ensemble. In doing so, we
      establish effective protocols for the analysis of transition rates in
      nonequilibrium quasisteady states. Transition rates between potential wells and
      also between phase-space elements are studied and found to exhibit distinct
      properties, the more coarse-grained potential wells being effectively further
      from equilibrium. In all cases the results from the boundary-driven system are
      close to the path-ensemble predictions, but the question of equivalence of the
      two remains open. 

PMID- 24580198
TI  - Particle-current fluctuations in a variant of the asymmetric Glauber model.
AB  - We study the total particle-current fluctuations in a one-dimensional stochastic
      system of classical particles consisting of branching and death processes which
      is a variant of asymmetric zero-temperature Glauber dynamics. The full spectrum
      of a modified Hamiltonian, whose minimum eigenvalue generates the large deviation
      function for the total particle-current fluctuations through a Legendre-Fenchel
      transformation, is obtained analytically. Three examples are presented and
      numerically exact results are compared to our analytical calculations. 

PMID- 24580199
TI  - Mechanical control of heat conductivity in molecular chains.
AB  - We discuss a possibility to control heat conductivity in molecular chains by
      means of external mechanical loads. To illustrate such possibilities we consider
      first well-studied one-dimensional chain with degenerate double-well potential of
      the nearest-neighbor interaction. We consider varying lengths of the chain with
      fixed number of particles. Number of possible energetically degenerate ground
      states strongly depends on the overall length of the chain, or, in other terms,
      on average length of the link between neighboring particles. These degenerate
      states correspond to mechanical equilibria; therefore, one can say that formation
      of such structures mimics a process of plastic deformation. We demonstrate that
      such modification of the chain length can lead to quite profound (almost
      fivefold) reduction of the heat conduction coefficient. Even more profound effect
      is revealed for a model with a single-well nonconvex potential. It is
      demonstrated that in a certain range of constant external forcing, this model
      becomes effectively double-well and has a multitude of possible states of
      equilibrium for fixed value of the external load. Due to this degeneracy, the
      heat-conduction coefficient can be reduced by two orders of magnitude. We suggest
      a mechanical model of a chain with periodic double-well potential, which allows
      control of the heat transport. The models considered may be useful for
      description of heat transfer in biological macromolecules and for control of the
      heat transport in microsystems. The possibility of the heat transport control in
      more realistic three-dimensional systems is illustrated by simulation of a three
      dimensional model of polymer alpha-helix. In this model, the mechanical
      stretching also brings about the structural inhomogeneity and, in turn, to
      essential reduction of the heat conductivity. 

PMID- 24580200
TI  - Path-integral approach to the Wigner-Kirkwood expansion.
AB  - We study the high-temperature behavior of quantum-mechanical path integrals.
      Starting from the Feynman-Kac formula, we derive a functional representation of
      the Wigner-Kirkwood perturbation expansion for quantum Boltzmann densities. As
      shown by its applications to different potentials, the presented expansion turns
      out to be quite efficient in generating analytic form of the higher-order
      expansion coefficients. To put some flesh on the bare bones, we apply the
      expansion to obtain basic thermodynamic functions of the one-dimensional
      anharmonic oscillator. Further salient issues, such as generalization to the
      Bloch density matrix and comparison with the more customary world-line
      formulation, are discussed. 

PMID- 24580201
TI  - Weak ergodicity breaking in an anomalous diffusion process of mixed origins.
AB  - The ergodicity breaking parameter is a measure for the heterogeneity among
      different trajectories of one ensemble. In this report, this parameter is
      calculated for fractional Brownian motion with a random change of time scale,
      often called "subordination." We show that this quantity is the same as the known
      continuous time random walks case. 

PMID- 24580202
TI  - Statistically interacting vacancy particles.
AB  - The equilibrium statistical mechanics of one-dimensional lattice gases with
      interactions of arbitrary range and shape between first-neighbor atoms is solved
      exactly on the basis of statistically interacting vacancy particles. Two sets of
      vacancy particles are considered. In one set all vacancies are of one-cell size.
      In the other set the sizes of vacancy particles match the separation between
      atoms. Explicit expressions are obtained for the Gibbs free energy and the
      distribution of spaces between atoms at thermal equilibrium. Applications to
      various types of interaction potentials are discussed, including long-range
      potentials that give rise to phase transitions. Extensions to hard rod systems
      are straightforward and are shown to agree with existing results for lattice
      models and their continuum limits. 

PMID- 24580203
TI  - Entropic stochastic resonance enables trapping under periodic confinement: a
      Brownian-dynamics study.
AB  - Entropically mediated phenomena are of emerging interest as a driving force for
      microscale and nanoscale transport, but their underlying stochastic nature makes
      them challenging to rationally manipulate and control. Stochastic resonance
      offers an intriguing avenue to overcome these difficulties by establishing a
      clear connection between the system response (the output) and an externally
      imposed driving force (the input). Previous studies have generally adopted a
      signal-processing viewpoint to classify the output in terms of a signal-to-noise
      ratio, but this link does not convey information that is immediately useful to
      infer parameters relevant to transport. Here we address this issue by applying
      Brownian-dynamics simulations to elucidate the residence time distribution
      encountered by a particle as it travels through a channel incorporating periodic
      constrictions. A sinusoidal longitudinal driving force is applied with a
      superimposed continuous orthogonal component, making it possible to identify
      frequency and amplitude conditions where temporal coherence with the particle's
      motion can be achieved. This resonant state reflects a synergistic combination of
      geometry and driving force that can be exploited to confine species at discrete
      locations, offering possibilities for directed manipulation. 

PMID- 24580204
TI  - Evidence of a robust universality class in the critical behavior of self
      propelled agents: metric versus topological interactions.
AB  - The nature of the interactions among self-propelled agents (SPA), i.e.,
      topological versus metric or a combination of both types, is a relevant open
      question in the field of self-organization phenomena. We studied the critical
      behavior of a Vicsek-like system of SPA given by a group of agents moving at
      constant speed and interacting among themselves under the action of a topological
      rule: each agent aligns itself with the average direction of its seven nearest
      neighbors, independent of the distance, under the influence of some noise. Based
      on both stationary and dynamic measurements, we provide strong evidence that both
      types of interactions are manifestations of the same phenomenon, which defines a
      robust universality class. Also, the cluster size distribution evaluated at the
      critical point shows a power-law behavior, and the exponent corresponding to the
      topological model is in excellent agreement with that of the metric one, further
      reinforcing our claim. Furthermore, we found that with topological interactions
      the average distance of influence between agents undergoes large fluctuations
      that diverge at the critical noise, thus providing clues about a mechanism that
      could be implemented by the agents to change their moving strategy. 

PMID- 24580205
TI  - Kovacs effect in the one-dimensional Ising model: a linear response analysis.
AB  - We analyze the so-called Kovacs effect in the one-dimensional Ising model with
      Glauber dynamics. We consider small enough temperature jumps, for which a linear
      response theory has been recently derived. Within this theory, the Kovacs hump is
      directly related to the monotonic relaxation function of the energy. The
      analytical results are compared with extensive Monte Carlo simulations, and an
      excellent agreement is found. Remarkably, the position of the maximum in the
      Kovacs hump depends on the fact that the true asymptotic behavior of the
      relaxation function is different from the stretched exponential describing the
      relevant part of the relaxation at low temperatures. 

PMID- 24580206
TI  - Large deviation function and fluctuation theorem for classical particle
      transport.
AB  - We analytically evaluate the large deviation function in a simple model of
      classical particle transfer between two reservoirs. We illustrate how the
      asymptotic long-time regime is reached starting from a special propagating
      initial condition. We show that the steady-state fluctuation theorem holds
      provided that the distribution of the particle number decays faster than an
      exponential, implying analyticity of the generating function and a discrete
      spectrum for its evolution operator. 

PMID- 24580207
TI  - Lower bounds on high-temperature diffusion constants from quadratically extensive
      almost-conserved operators.
AB  - We prove a general theorem which provides a strict lower bound on high
      temperature Green-Kubo diffusion constants in locally interacting quantum lattice
      systems, under the assumption of existence of a quadratically extensive almost
      conserved quantity: an operator whose commutator with the lattice Hamiltonian is
      localized on the boundary sites only. We explicitly demonstrate and compute such
      a bound in two important models in one dimension: in the (isotropic) Heisenberg
      spin 1/2 chain and in the fermionic Hubbard chain. 

PMID- 24580208
TI  - Thermodynamic feature of a Brownian heat engine operating between two heat baths.
AB  - A generalized theory of nonequilibrium thermodynamics for a Brownian motor
      operating between two different heat baths is presented. Via a simple
      paradigmatic model, we not only explore the thermodynamic feature of the engine
      in the regime of the nonequilibrium steady state but also study the short time
      behavior of the system for either the isothermal case with load or, in general,
      the nonisothermal case with or without load. Many elegant thermodynamic theories
      can be checked via the present model. Furthermore the dependence of the velocity,
      the efficiency, and the performance of the refrigerator on time t is examined.
      Our study reveals a current reversal due to time t. In the early system
      relaxation period, the model works neither as a heat engine nor as a refrigerator
      and only after a certain period of time does the model start functioning as a
      heat engine or as a refrigerator. The performance of the engine also improves
      with time and at steady state the engine manifests a higher efficiency or
      performance as a refrigerator. Furthermore the effect of energy exchange via the
      kinetic energy on the performance of the heat engine is explored. 

PMID- 24580209
TI  - Thermostatistical description of small systems in nonequilibrium conditions:
      energy conversion and harvesting.
AB  - Hysteresis cycles are very important features of energy conversion and harvesting
      devices, such as batteries. The efficiency of these may be strongly affected by
      the physical size of the system. Here, we show that in systems which are small
      enough, the existence of physical boundaries which produce nonhomogeneities of
      the interaction potential gives rise to inflections and barriers in the
      associated free energy. This in turn brings on irreversible processes which can
      be triggered under suitable external conditions imposed by a heat bath. As an
      example, by controlling the temperature, the state of a small system may be
      impelled to oscillate between two different structural configurations or
      aggregation states avoiding equilibrium coexistence and therefore dissipating
      energy. This cyclical behavior associated with a hysteresis cycle may be
      prototypical of energy conversion, storage, or generating nanodevices, as
      exemplified by Li-ion insertion batteries. 

PMID- 24580210
TI  - Quenched disorder forbids discontinuous transitions in nonequilibrium low
      dimensional systems.
AB  - Quenched disorder affects significantly the behavior of phase transitions. The
      Imry-Ma-Aizenman-Wehr-Berker argument prohibits first-order or discontinuous
      transitions and their concomitant phase coexistence in low-dimensional
      equilibrium systems in the presence of random fields. Instead, discontinuous
      transitions become rounded or even continuous once disorder is introduced. Here
      we show that phase coexistence and first-order phase transitions are also
      precluded in nonequilibrium low-dimensional systems with quenched disorder:
      discontinuous transitions in two-dimensional systems with absorbing states become
      continuous in the presence of quenched disorder. We also study the universal
      features of this disorder-induced criticality and find them to be compatible with
      the universality class of the directed percolation with quenched disorder. Thus,
      we conclude that first-order transitions do not exist in low-dimensional
      disordered systems, not even in genuinely nonequilibrium systems with absorbing
      states. 

PMID- 24580211
TI  - Spin-1 Hopfield model under a random field.
AB  - The goal of the present work is to investigate the role of trivial disorder and
      nontrivial disorder in the three-state Hopfield model under a Gaussian random
      field. In order to control the nontrivial disorder, the Hebb interaction is used.
      This provides a way to control the system frustration by means of the parameter
      a=p/N, varying from trivial randomness to a highly frustrated regime, in the
      thermodynamic limit. We performed the thermodynamic analysis using the one-step
      replica-symmetry-breaking mean field theory to obtain the order parameters and
      phase diagrams for several strengths of a, the anisotropy constant, and the
      random field.

PMID- 24580212
TI  - Post-Markovian quantum master equations from classical environment fluctuations.
AB  - In this paper we demonstrate that two commonly used phenomenological post
      Markovian quantum master equations can be derived without using any perturbative
      approximation. A system coupled to an environment characterized by self-classical
      configurational fluctuations, the latter obeying a Markovian dynamics, defines
      the underlying physical model. Both Shabani-Lidar equation [A. Shabani and D. A.
      Lidar, Phys. Rev. A 71, 020101(R) (2005)] and its associated approximated
      integrodifferential kernel master equation are obtained by tracing out two
      different bipartite Markovian Lindblad dynamics where the environment
      fluctuations are taken into account by an ancilla system. Furthermore, conditions
      under which the non-Markovian system dynamics can be unraveled in terms of an
      ensemble of measurement trajectories are found. In addition, a non-Markovian
      quantum jump approach is formulated. Contrary to recent analysis [L. Mazzola, E.
      M. Laine, H. P. Breuer, S. Maniscalco, and J. Piilo, Phys. Rev. A 81, 062120
      (2010)], we also demonstrate that these master equations, even with exponential
      memory functions, may lead to non-Markovian effects such as an environment-to
      system backflow of information if the Hamiltonian system does not commutate with
      the dissipative dynamics. 

PMID- 24580213
TI  - Percolation through voids around overlapping spheres: a dynamically based finite
      size scaling analysis.
AB  - The percolation threshold for flow or conduction through voids surrounding
      randomly placed spheres is calculated. With large-scale Monte Carlo simulations,
      we give a rigorous continuum treatment to the geometry of the impenetrable
      spheres and the spaces between them. To properly exploit finite-size scaling, we
      examine multiple systems of differing sizes, with suitable averaging over
      disorder, and extrapolate to the thermodynamic limit. An order parameter based on
      the statistical sampling of stochastically driven dynamical excursions and
      amenable to finite-size scaling analysis is defined, calculated for various
      system sizes, and used to determine the critical volume fraction phic=0.0317+/
      0.0004 and the correlation length exponent nu=0.92+/-0.05. 

PMID- 24580214
TI  - Splitting probabilities and interfacial territory covered by two-dimensional and
      three-dimensional surface-mediated diffusion.
AB  - We consider the mean territory covered by a particle that performs surface
      mediated diffusion inside a spherical confining domain (in two and three
      dimensions) before exit through an opening on the surface. This quantity can be
      expressed in terms of the splitting probability between two targets on the
      surface. We derive a general formula that relates this splitting probability to
      the mean first passage time to a single target that has been recently calculated
      for such a surface-mediated diffusion process. This formula is exact for
      pointlike targets and is shown to be accurate for extended targets. The mean
      covered territory is then found and analyzed for an arbitrary extension of the
      exit region in both two- and three-dimensional spherical domains. 

PMID- 24580215
TI  - Equilibrium dynamics of the Dean-Kawasaki equation: mode-coupling theory and its
      extension.
AB  - We extend a previously proposed field-theoretic self-consistent perturbation
      approach for the equilibrium dynamics of the Dean-Kawasaki equation presented in
      [Kim and Kawasaki, J. Stat. Mech. (2008) P02004]. By taking terms missing in the
      latter analysis into account we arrive at a set of three new equations for
      correlation functions of the system. These correlations involve the density and
      its logarithm as local observables. Our new one-loop equations, which must
      carefully deal with the noninteracting Brownian gas theory, are more general than
      the historic mode-coupling one in that a further approximation corresponding to
      Gaussian density fluctuations leads back to the original mode-coupling equation
      for the density correlations alone. However, without performing any further
      approximation step, our set of three equations does not feature any ergodic
      nonergodic transition, as opposed to the historical mode-coupling approach. 

PMID- 24580216
TI  - Collisional model for granular impact dynamics.
AB  - When an intruder strikes a granular material from above, the grains exert a
      stopping force which decelerates and stops the intruder. Many previous studies
      have used a macroscopic force law, including a drag force which is quadratic in
      velocity, to characterize the decelerating force on the intruder. However, the
      microscopic origins of the force-law terms are still a subject of debate. Here,
      drawing from previous experiments with photoelastic particles, we present a model
      which describes the velocity-squared force in terms of repeated collisions with
      clusters of grains. From our high speed photoelastic data, we infer that
      "clusters" correspond to segments of the strong force network that are excited by
      the advancing intruder. The model predicts a scaling relation for the velocity
      squared drag force that accounts for the intruder shape. Additionally, we show
      that the collisional model predicts an instability to rotations, which depends on
      the intruder shape. To test this model, we perform a comprehensive experimental
      study of the dynamics of two-dimensional granular impacts on beds of photoelastic
      disks, with different profiles for the leading edge of the intruder. We
      particularly focus on a simple and useful case for testing shape effects by using
      triangular-nosed intruders. We show that the collisional model effectively
      captures the dynamics of intruder deceleration and rotation; i.e., these two
      dynamical effects can be described as two different manifestations of the same
      grain-scale physical processes. 

PMID- 24580217
TI  - Rheology of weakly vibrated granular media.
AB  - We probe the rheology of weakly vibrated granular flows as function of flow rate,
      vibration strength, and pressure by performing experiments in a vertically
      vibrated split-bottom shear cell. For slow flows, we establish the existence of a
      vibration-dominated granular flow regime, where the driving stresses smoothly
      vanish as the driving rate is diminished. We distinguish three qualitatively
      different vibration-dominated rheologies, most strikingly a regime where the
      shear stresses no longer are proportional to the pressure. 

PMID- 24580218
TI  - Force-chain distributions in granular systems.
AB  - We study experimentally the distributions of force chains in granular materials,
      which are slightly different in sheared systems compared to isotropically
      compressed systems, especially at the tails, reflecting the shear-induced
      anisotropy of the contact force network. Ignoring this anisotropy allows us to
      establish a relationship between the mean force-chain length Lm and the average
      contact number Z of particles for both systems, independent of the system size.
      We also demonstrate that force-chain distributions are not related to the
      exponential-like distributions of stresses. 

PMID- 24580219
TI  - Characterization of wave propagation in elastic and elastoplastic granular
      chains.
AB  - For short duration impulse loadings, elastic granular chains are known to support
      solitary waves, while elastoplastic chains have recently been shown to exhibit
      two force decay regimes [ Pal, Awasthi and Geubelle Granular Matter 15 747
      (2013)]. In this work, the dynamics of monodisperse elastic and elastoplastic
      granular chains under a wide range of loading conditions is studied, and two
      distinct response regimes are identified in each of them. In elastic chains, a
      short loading duration leads to a single solitary wave propagating down the
      chain, while a long loading duration leads to the formation of a train of
      solitary waves. A simple model is developed to predict the peak force and wave
      velocity for any loading duration and amplitude. In elastoplastic chains, wave
      trains form even for short loading times due to a mechanism distinct from that in
      elastic chains. A model based on energy balance predicts the decay rate and
      transition point between the two decay regimes. For long loading durations,
      loading and unloading waves propagate along the chain, and a model is developed
      to predict the contact force and particle velocity. 

PMID- 24580220
TI  - Effect of elastic vibrations on normal head-on collisions of isothermal spheres.
AB  - We numerically investigate head-on collisions of isothermal viscoelastic spheres.
      We find that the restitution coefficient oscillates against the impact speed if
      the solid viscosity inside the sphere is small enough. We confirm that the
      oscillation arises from the resonance between the duration of contact and the
      eigenfrequencies of the sphere. This oscillation disappears if there exists the
      strong solid viscosity in spheres. We also find that a sinusoidal behavior of the
      restitution coefficient against the initial phase in the eigenmodes for
      collisions between a thermally activated sphere and a flat wall. As a result, the
      restitution coefficient can exceed unity if the impact speed of the colliding
      sphere is nearly equal to or slower than the thermal speed. We have confirmed the
      existence of the fluctuation theorem for impact processes through our simulation.

PMID- 24580221
TI  - Phonon dispersion and elastic moduli of two-dimensional disordered colloidal
      packings of soft particles with frictional interactions.
AB  - Particle tracking and displacement covariance matrix techniques are employed to
      investigate the phonon dispersion relations of two-dimensional colloidal glasses
      composed of soft, thermoresponsive microgel particles whose temperature-sensitive
      size permits in situ variation of particle packing fraction. Bulk, B, and shear,
      G, moduli of the colloidal glasses are extracted from the dispersion relations as
      a function of packing fraction, and variation of the ratio G/B with packing
      fraction is found to agree quantitatively with predictions for jammed packings of
      frictional soft particles. In addition, G and B individually agree with numerical
      predictions for frictional particles. This remarkable level of agreement enabled
      us to extract an energy scale for the interparticle interaction from the
      individual elastic constants and to derive an approximate estimate for the
      interparticle friction coefficient. 

PMID- 24580222
TI  - Effect of concentration polarization on permselectivity.
AB  - In this paper, the variation of permselectivity in the course of concentration
      polarization is systematically analyzed for a three-layer membrane system
      consisting of a nonperfectly permselective ion exchange membrane, homogeneous or
      heterogeneous, flanked by two diffusion layers of a binary univalent electrolyte.
      For a heterogeneous membrane, an ionic transport model is proposed, which is
      amenable to analytical treatment. In this model, assuming a constant fixed charge
      in the membrane and disregarding water splitting, the entire transport problem is
      reduced to solution of a single algebraic equation for the counterion transport
      number. It is concluded that for both types of membrane the concentration
      polarization may significantly affect the permselectivity of the system through
      the effects of the induced nonuniformity of the coion diffusion flux in the
      membrane (convexity of the coion concentration profile) and varying membrane
      solution interface concentration. While the former is significant for low
      membrane fixed charge density, for a heterogeneous membrane, the latter might be
      considerably affected by the flux focusing effect at the permeable membrane
      segments. 

PMID- 24580223
TI  - Induced cooperative motions in a medium driven at the nanoscale: searching for an
      optimum excitation period.
AB  - Recent results have shown the appearance of induced cooperative motions called
      dynamic heterogeneity during the isomerization of diluted azobenzene molecules in
      a host glass-former. In this paper, we raise the issue of the coupling between
      these "artificial" heterogeneities and the isomerization period. How do these
      induced heterogeneities differ in the saturation regime and in the linear
      response regime? Is there a maximum of the heterogeneous motion versus the
      isomerization rate, and why? Is the heterogeneity evolution with the
      isomerization rate connected with the diffusion or relaxation time evolution? We
      use out-of-equilibrium molecular dynamics simulations to answer these questions.
      We find that the heterogeneity increases in the linear response regime for large
      isomerization periods and small perturbations. In contrast, the heterogeneity
      decreases in the saturation regime, i.e., when the isomerization half-period
      (taup/2) is smaller than the relaxation time of the material (taualpha). This
      result enables a test of the effect of cooperative motions on the dynamics using
      the chromophores as Maxwell demons that destroy or stimulate the cooperative
      motions. Because the heterogeneities increase in the linear regime and then
      decrease in the saturation regime, we find a maximum for taup/2~taualpha. The
      induced excitation concentration follows a power-law evolution versus the
      isomerization rate and then saturates. As a consequence, the alpha relaxation
      time is related to the excitation concentration with a power law, a result in
      qualitative agreement with recent findings in constrained models. This result
      supports a common origin for the heterogeneities with constrained models and a
      similar relation to the excitation concentration. 

PMID- 24580224
TI  - Visualizing the strain evolution during the indentation of colloidal glasses.
AB  - We use an analog of nanoindentation on a colloidal glass to elucidate the
      incipient plastic deformation of glasses. By tracking the motion of the
      individual particles in three dimensions, we visualize the strain field and glass
      structure during the emerging deformation. At the onset of flow, we observe a
      power-law distribution of strain indicating strongly correlated deformation, and
      reflecting a critical state of the glass. At later stages, the strain acquires a
      Gaussian distribution, indicating that plastic events become uncorrelated.
      Investigation of the glass structure using both static and dynamic measures shows
      a weak correlation between the structure and the emerging strain distribution.
      These results indicate that the onset of plasticity is governed by strong power
      law correlations of strain, weakly biased by the heterogeneous glass structure. 

PMID- 24580225
TI  - Hybrid atomistic simulation of fluid uptake in a deformable solid.
AB  - Fluid imbibition via diffusion in a deformable solid results in solid stresses
      that may, in turn, alter subsequent fluid uptake. To examine this interplay
      between diffusional and elastic fields, we employed a hybrid Monte Carlo
      molecular dynamics scheme to model the coupling of a fluid reservoir to a
      deformable solid, and then simulated the resulting fluid permeation into the
      solid. By monitoring the instantaneous structure factor and solid dimensions, we
      were able to determine the compositional strain associated with imbibition, and
      the diffusion coefficient in the Fickian regime was obtained from the time
      dependence of the fluid uptake. Finally, for large, mobile fluid atoms, a non
      Fickian regime was highlighted and possible mechanisms for this behavior were
      identified. 

PMID- 24580227
TI  - Effect of finite ion sizes in an electrostatic potential distribution for a
      charged soft surface in contact with an electrolyte solution.
AB  - We provide a theory to analyze the impact of finite ion sizes (or steric effect)
      in electrostatic potential distribution for a charged soft surface in contact
      with an electrolyte solution. The theory is based on a free energy model that
      appropriately accounts for the contribution of finite ion sizes as well as the
      structural characteristics of a soft interface, represented by a combination of a
      rigid surface and a fixed charge layer (FCL), with the FCL being in contact with
      an electrolyte solution forming an electric double layer (EDL). This FCL contains
      a particular kind of ion which is impermeable to the electrolyte solution, and
      this impermeability is quantified in terms of the corresponding Donnan potential
      of the "membrane" represented by the FCL-electrolyte interface. We find that
      consideration of the finite ion size increases the magnitude of this Donnan
      potential, with the extent of increase being dictated by three length scales,
      namely, the thickness of the FCL, the thickness of the electrolyte EDL, and the
      thickness of an equivalent EDL within the FCL. Such regulation of the Donnan
      potential strongly affects the distribution of the permeable electrolyte ions
      within the FCL, which in turn will have significant implications in several
      processes involving "soft" biological membranes. 

PMID- 24580226
TI  - Field-induced sublimation in perfect two-dimensional colloidal crystals.
AB  - Phase transitions in two-dimensional (2D) systems are of considerable fundamental
      and practical importance. However, the kinetics of these processes are difficult
      to predict and understand, even in simple systems for which equilibrium states
      are properly described, owing to the difficulty of studying crystallites with
      single-particle resolution and free of defects. Here we introduce an alternative
      method for the sublimation of 2D colloidal crystallites by a sudden induction of
      repulsive forces between the particles. The sublimation kinetics, studied in real
      space by microscopy and by computer simulations, shows a scaling behavior that
      suggests a universal mechanism fundamentally different from the one usually
      accepted for thermal sublimation. The universal behavior found for the early
      stages of the process may be useful for understanding the dynamic features of
      particle systems at liquid interfaces and for designing technological
      applications without the need of performing extensive experimental studies. 

PMID- 24580228
TI  - Laser-speckle-visibility acoustic spectroscopy in soft turbid media.
AB  - We image the evolution in space and time of an acoustic wave propagating along
      the surface of turbid soft matter by shining coherent light on the sample. The
      wave locally modulates the speckle interference pattern of the backscattered
      light, which is recorded using a camera. We show both experimentally and
      theoretically how the temporal and spatial correlations in this pattern can be
      analyzed to obtain the acoustic wavelength and attenuation length. The technique
      is validated using shear waves propagating in aqueous foam. It may be applied to
      other kinds of acoustic waves in different forms of turbid soft matter such as
      biological tissues, pastes, or concentrated emulsions. 

PMID- 24580229
TI  - Frozen-wave instability in near-critical hydrogen subjected to horizontal
      vibration under various gravity fields.
AB  - The frozen-wave instability which appears at a liquid-vapor interface when a
      harmonic vibration is applied in a direction tangential to it has been less
      studied until now. The present paper reports experiments on hydrogen (H2) in
      order to study this instability when the temperature is varied near its critical
      point for various gravity levels. Close to the critical point, a liquid-vapor
      density difference and surface tension can be continuously varied with
      temperature in a scaled, universal way. The effect of gravity on the height of
      the frozen waves at the interface is studied by performing the experiments in a
      magnetic facility where effective gravity that results from the coupling of the
      Earth's gravity and magnetic forces can be varied. The stability diagram of the
      instability is obtained. The experiments show a good agreement with an inviscid
      model [Fluid Dyn. 21 849 (1987)], irrespective of the gravity level. It is
      observed in the experiments that the height of the frozen waves varies weakly
      with temperature and increases with a decrease in the gravity level, according to
      a power law with an exponent of 0.7. It is concluded that the wave height becomes
      of the order of the cell size as the gravity level is asymptotically decreased to
      zero. The interface pattern thus appears as a bandlike pattern of alternate
      liquid and vapor phases, a puzzling phenomenon that was observed with CO2 and H2
      near their critical point in weightlessness [Acta Astron. 61 1002 (2007);
      Europhys. Lett. 86 16003 (2009)].

PMID- 24580230
TI  - Phase behavior of an amphiphilic fluid.
AB  - We invoke mean-field density functional theory (DFT) to investigate the phase
      behavior of an amphiphilic fluid composed of a hard-sphere core plus a
      superimposed anisometric Lennard-Jones perturbation. The orientation dependence
      of the interactions consists of a contribution analogous to the interaction
      potential between a pair of "spins" in the classical, three-dimensional
      Heisenberg fluid and another one reminiscent of the interaction between (electric
      or magnetic) point dipoles. At fixed orientation both contributions are short
      range in nature decaying as r-6 (r being the separation between the centers of
      mass of a pair of amphiphiles). Based upon two mean-field-like approximations for
      the pair correlation function that differ in the degree of sophistication we
      derive expressions for the phase boundaries between various isotropic and polar
      phases that we solve numerically by the Newton-Raphson method. For sufficiently
      strong coupling between the Heisenberg "spins" both mean-field approximations
      generate three topologically different and generic types of phase diagrams that
      are observed in agreement with earlier work [see, for example, Tavares et al.,
      Phys. Rev. E 52, 1915 (1995)]. Whereas the dipolar contribution alone is
      incapable of stabilizing polar phases on account of its short-range nature it is
      nevertheless important for details of the phase diagram such as location of the
      gas-isotropic liquid critical point, triple, and tricritical points. By tuning
      the dipolar coupling constant suitably one may, in fact, switch between
      topologically different phase diagrams. Employing also Monte Carlo simulations in
      the isothermal-isobaric ensemble the general topology of the DFT phase diagrams
      is confirmed. 

PMID- 24580231
TI  - Soft beams: when capillarity induces axial compression.
AB  - We study the interaction of an elastic beam with a liquid drop in the case where
      bending and extensional effects are both present. We use a variational approach
      to derive equilibrium equations and constitutive relation for the beam. This
      relation is shown to include a term due to surface energy in addition to the
      classical Young's modulus term, leading to a modification of Hooke's law. At the
      triple point where solid, liquid, and vapor phases meet, we find that the
      external force applied on the beam is parallel to the liquid-vapor interface.
      Moreover, in the case where solid-vapor and solid-liquid interface energies do
      not depend on the extension state of the beam, we show that the extension in the
      beam is continuous at the triple point and that the wetting angle satisfies the
      classical Young-Dupre relation. 

PMID- 24580232
TI  - Droplet pattern and condensation gradient around a humidity sink.
AB  - We describe the evolution of a water drop saturated with NaCl and the growth of
      pure water droplets in a breath figure pattern (BF) condensing around it. This
      salty drop acts as a humidity sink, inhibiting the BF inside a ring at a distance
      r=delta from the sink center and slowing down BF growth outside the ring. The
      initial salty drop is taken either from a salt-saturated solution (type I
      experiment) or by placing an NaCl crystal on the substrate (type II experiment).
      The results are similar, provided that the initial time for type II evolution is
      taken at the end of the crystal dissolution. The evolution of the salty drop
      radius R is deduced from the establishment of a three-dimensional hyperbolic
      concentration profile around the salty drop. This profile scales with r/delta.
      Accounting for the salt concentration decrease with salty drop growth, R is seen
      to grow as t5. In the region r>delta, water droplets nucleate and grow. The rate
      of evolution of the water droplets at constant r/delta can be used to determine
      the local water pressure. The corresponding data reasonably agree with a
      hyperbolic water vapor profile around the salty drop. These results can be
      applied to the growth of BF patterns to determine whether hyperbolic or linear
      water vapor profiles apply. 

PMID- 24580233
TI  - Longitudinal versus polar wrinkling of core-shell fibers with anisotropic size
      mismatches.
AB  - We consider a fiber made of a soft elastic material, encased in a stiff elastic
      shell (core-shell geometry). If the core and shell dimensions are mismatched,
      e.g., because the core shrinks while the shell does not, but the two remain
      attached, then an elastic instability is triggered whereby wrinkles may appear on
      the shell. The wrinkle orientation may be longitudinal (along the fiber axis),
      polar (along the fiber perimeter), or a mixture of both, depending on the fiber's
      geometrical and material parameters. Here we investigate under what conditions
      longitudinal or polar wrinkling will occur. 

PMID- 24580234
TI  - Rough-smooth-rough dynamic interface growth in supported lipid bilayers.
AB  - The role of lipid bilayer viscoelasticity and the substrate-bilayer interactions
      on the spreading behavior of supported phospholipid bilayer membranes is studied
      using fluorescence microscopy. Unlike the monotonic roughening observed on silica
      or in other dynamic interface growth systems, a unique rough-smooth-rough (RSR)
      interface transition occurred on chromium oxide with a roughness exponent of 0.45
      +/- 0.04. This RSR transition is attributed to the elasticity of the lipid
      bilayer which is initially under compression due to surface interactions, and is
      well approximated by adding an elastic term to the quenched noise Edwards
      Wilkinson equation. A phase diagram depicting the conditions necessary to observe
      RSR transitions in dynamic interface systems is derived, revealing the classes of
      dynamically evolving systems is broader than previously thought, and the
      viscoelastic nature of the lipid bilayer may play a role in supported membrane
      behavior. 

PMID- 24580235
TI  - Phase-field-crystal simulation of nonequilibrium crystal growth.
AB  - By using the phase field crystal model, we simulate the morphological transition
      of the crystal growth of equilibrium crystal shape, dendrite, and spherical
      crystal shape. The relationship among growth morphology, velocity, and density
      distribution is investigated. The competition between interface energy anisotropy
      and interface kinetic anisotropy gives rise to the pattern selection of dendritic
      growth in the diffusion controlled regime under low-crystal-growth velocities.
      The trapping effect in density diffusion suppresses morphological instabilities
      under high-crystal-growth velocities, resulting in isotropic growth of spherical
      crystal. Finally, a morphological phase diagram of crystal growth is constructed
      as function of the phase field crystal model parameters. 

PMID- 24580236
TI  - Sliding drops across alternating hydrophobic and hydrophilic stripes.
AB  - We perform a joint numerical and experimental study to systematically
      characterize the motion of 30 MUl drops of pure water and of ethanol in water
      solutions, sliding over a periodic array of alternating hydrophobic and
      hydrophilic stripes with a large wettability contrast and a typical width of
      hundreds of microns. The fraction of the hydrophobic areas has been varied from
      about 20% to 80%. The effects of the heterogeneous patterning can be described by
      a renormalized value of the critical Bond number, i.e., the critical
      dimensionless force needed to depin the drop before it starts to move. Close to
      the critical Bond number we observe a jerky motion characterized by an evident
      stick-slip dynamics. As a result, dissipation is strongly localized in time, and
      the mean velocity of the drops can easily decrease by an order of magnitude
      compared to the sliding on the homogeneous surface. Lattice Boltzmann numerical
      simulations are crucial for disclosing to what extent the sliding dynamics can be
      deduced from the computed balance of capillary, viscous, and body forces by
      varying the Bond number, the surface composition, and the liquid viscosity.
      Beyond the critical Bond number, we characterize both experimentally and
      numerically the dissipation inside the droplet by studying the relation between
      the average velocity and the applied volume forces. 

PMID- 24580237
TI  - Tuning the ordered states of folded rods by isotropic confinement.
AB  - The packing of elastic objects is increasingly studied in the framework of out-of
      equilibrium statistical mechanics and thus these appear to be similar to glassy
      systems. Here, we present a two-dimensional experiment whereby a rod is confined
      by a parabolic potential. The setup enables spanning a wide range of folded
      configurations of the rod. Measurements of the distributions of length and
      curvature in the system reveal the importance of a stacking process whereby many
      layers of the rod are grouped into branches. The geometrical order of patterns
      increases with the confinement strength. Measurements of the distributions of
      energies lead to the definition of an energy scale that is correlated with the
      elastic energy of the stacked parts of the rod. This scale imposes energy
      partition in the system and might be relevant to the framework of the
      thermodynamics of disordered systems. Following these observations, we describe
      the patterns as excited states of a ground state corresponding to the most
      ordered geometry. Eventually, we provide evidence that the disordered state of a
      folded rod becomes spontaneously closer to the ground state as confinement is
      increased. 

PMID- 24580238
TI  - Stability of a directional solidification front in subdiffusive media.
AB  - The efficiency of crystal growth in alloys is limited by the morphological
      instability, which is caused by a positive feedback between the interface
      deformation and the diffusive flux of solute at the front of the phase
      transition. Usually this phenomenon is described in the framework of the normal
      diffusion equation, which stems from the linear relation between time and the
      mean squared displacement of molecules <x2(t)>~K1t (K1 is the classical diffusion
      coefficient) that is characteristic of Brownian motion. However, in some media
      (e.g., in gels and porous media) the random walk of molecules is hindered by
      obstacles, which leads to another power law, <x2(t)>~Kalphatalpha, where
      0<alpha<=1. As a result, the diffusion is anomalous, and it is governed by an
      integro-differential equation including a fractional derivative in time variable,
      i.e., a memory. In the present work, we investigate the stability of a
      directional solidification front in the case of an anomalous diffusion. Linear
      stability of a moving planar directional solidification front is studied, and a
      generalization of the Mullins-Sekerka stability criterion is obtained. Also, an
      asymptotic nonlinear long-wave evolution equation of Sivashinsky's type, which
      governs the cellular structures at the interface, is derived. 

PMID- 24580239
TI  - Multicomponent phase-field model for extremely large partition coefficients.
AB  - We develop a multicomponent phase-field model specially formulated to robustly
      simulate concentration variations from molar to atomic magnitudes across an
      interface, i.e., partition coefficients in excess of 10+/-23 such as may be the
      case with species which are predominant in one phase and insoluble in the other.
      Substitutional interdiffusion on a normal lattice and concurrent interstitial
      diffusion are included. The composition in the interface follows the approach of
      Kim, Kim, and Suzuki [Phys. Rev. E 60, 7186 (1999)] and is compared to that of
      Wheeler, Boettinger, and McFadden [Phys. Rev. A 45, 7424 (1992)] in the context
      of large partitioning. The model successfully reproduces analytical solutions for
      binary diffusion couples and solute trapping for the demonstrated cases of
      extremely large partitioning. 

PMID- 24580240
TI  - Effect of a bias electric field on the structure and dielectric response of the
      ferroelectric smectic-A liquid crystal in thin planar cells.
AB  - The phenomenological continuum model is used to study the director structure and
      dielectric response of the ferroelectric smectic-A phase in thin planar cells.
      The frequency of the phase mode and the dielectric permittivity are calculated
      numerically as a function of the bias external DC electric field, cell thickness,
      the strength of polar surface anchoring, and the ratio between the bend and splay
      elastic constants. The theoretically obtained dependencies are in agreement with
      the recently reported experimental measurements, which show that in thin planar
      cells both the phase mode frequency and the dielectric permittivity decrease with
      increasing external bias electric field. 

PMID- 24580241
TI  - Electric-field-induced patterns and their temperature dependence in a bent-core
      liquid crystal.
AB  - Two kinds of electroconvection patterns in an ether-bridged bent-core nematic
      liquid crystal material (BCN), which appear in different frequency ranges, are
      examined and compared. One is a longitudinal pattern with the stripes parallel to
      the orientation of the BCN and with a periodicity of approximately the cell
      thickness, occurring in the high-frequency range of several hundreds Hz; the
      other one is oblique stripes, which results in a zigzag pattern, and appears in
      the low-frequency range of several tens Hz. In addition, within an intermediate
      frequency range, transformations from oblique to longitudinal and then to normal
      stripes occur at increased ac voltages. In particular, we investigated the
      temperature behavior of longitudinal and oblique stripes: When the temperature T
      increases and approaches the clearing temperature Tc, the contrast of the domains
      is enhanced and the frequency range of existence becomes wider, while the onset
      voltages increase only moderately instead of diverging, thus suggesting an
      isotropic mechanism of pattern formation. 

PMID- 24580242
TI  - Light-induced pitch transitions in photosensitive cholesteric liquid crystals:
      effects of anchoring energy.
AB  - We experimentally study how the cholesteric pitch P depends on the equilibrium
      pitch P0 in planar liquid crystal (LC) cells with both strong and semistrong
      anchoring conditions. The cholesteric phase was induced by dissolution in the
      nematic LC of the right-handed chiral dopant 7-dehydrocholesterol (7-DHC,
      provitamin D3) which transforms to left-handed tachysterol under the action of uv
      irradiation at the wavelength of 254 nm. By using the model of photoreaction
      kinetics we obtain the dependencies of isomer concentrations and, therefore, of
      the equilibrium pitch on the uv irradiation dose. The cholesteric pitch was
      measured as a function of irradiation time using the polarimetry method. In this
      method, the pitch is estimated from the experimental data on the irradiation time
      dependence of the ellipticity of light transmitted through the LC cells. It is
      found that the resulting dependence of the twist parameter 2D/P (D is the cell
      thickness) on the free twisting number parameter 2D/P0 shows jumplike behavior
      and agrees well with the known theoretical results for the anchoring potential of
      Rapini-Papoular form. 

PMID- 24580243
TI  - Laser-induced instabilities in liquid crystal cells with a photosensitive
      substrate.
AB  - Liquid crystal layers sandwiched between a reference plate and a photosensitive
      substrate were investigated. We focused on the reverse geometry, where the cell
      was illuminated by a laser beam from the reference side. In planar cells both
      static and dynamic instabilities occurred, depending on the angle between the
      laser polarization and the director orientation on the reference plate. In cells
      where the molecules were aligned along the normal of the reference plate, a
      dynamic pattern was observed at all angles of polarization. A simple model based
      on a photoinduced surface torque accounts for the findings. Light scattering
      studies revealed some basic properties of the instabilities. 

PMID- 24580244
TI  - Molecular tilt near nanoparticles in the smectic-A phase of a de Vries liquid
      crystalline compound.
AB  - We show how the inclusions of the nanoparticles or the clusters of nanoparticles
      in the liquid-crystalline smectic-A phase lead to layer deformations and may
      create a tilt in their vicinity, thus inducing locally a smectic-A-smectic-C
      transition. We have studied a freestanding film of "de Vries" compound, which
      exhibits the smectic-A-smectic-C transition without layer shrinkage, mixed with
      functionalized gold nanoparticles. The tilt induced by nanoparticle clusters,
      which decorate the edge dislocations, has been observed in the smectic-A phase.
      The tilt of liquid-crystal molecules near nanoparticles is a consequence of
      interaction of liquid-crystalline molecules with the surface of nanoparticles.
      The observed tilt may prove the concept of existence of a disordered tilt in the
      smectic-A phase of de Vries compounds. The tilt distribution near nanoparticles
      is discussed using both the smectic-A elasticity and local smectic-A-smectic-C
      transition. 

PMID- 24580245
TI  - Effect of anisotropic lattice deformation on the Kerr coefficient of polymer
      stabilized blue-phase liquid crystals.
AB  - We investigate the effect of anisotropic lattice deformation on the Kerr
      coefficient of polymer-stabilized blue-phase liquid crystals (PSBP-LCs). PSBPs
      with orthorhombic and tetragonal symmetry were prepared by polymer-stabilizing a
      blue-phase liquid crystal under electrostriction. Both orthorhombic and
      tetragonal PSBPs showed smaller Kerr coefficients than the cubic PSBP, despite an
      increase in the unit cell volume caused by the elongation of the lattice along
      the direction of light propagation. Our results indicate that the Kerr
      coefficient of PSBPs is not determined simply by the volume of the unit lattice
      but by the lattice size perpendicular to the direction of light propagation. 

PMID- 24580246
TI  - Micro- and nanofibers and liquid crystals for light-scattering shutters:
      simulation of electro-optical properties.
AB  - This work demonstrates the feasibility of using polymeric micro- and nanofiber
      composed films and liquid crystals as electrically switchable scattering light
      shutters. We present a concept of electro-optic device based on an innovative
      combination of two mature technologies: optics of nematic liquid crystals and
      electrospinning of nanofibers. These devices have electric and optical
      characteristics far superior to other comparable methods. The simulation
      presented shows results that are highly consistent with those of experiments and
      that explain the working mechanism of the devices. 

PMID- 24580247
TI  - Birefringence-induced wavelength mismatch between the polarization rotation and
      resonant modes in magnetophotonic structures containing nematic layers.
AB  - The present work is devoted to the study of spectral characteristics of normal
      incident light transmitted by a multilayered structure composed of an alternated
      sequence of nematic and magnetic layers presenting a central magneto-optical
      defect. Using the Berreman 4 * 4 matrix formalism, we numerically obtain the
      transmission spectrum and the polarization rotation angle of the system as a
      function of the nematic optical axis direction. Our results reveal the emergence
      of a shift between the wavelengths of the resonant mode and polarization rotation
      angle, which strongly depends on the birefringence of the nematic layers. In
      particular, we show the existence of distinct regimes for the wavelength mismatch
      between the transmission of resonant modes and the maximum polarization rotation
      angle, which are governed by the ordinary and extraordinary refractive indices of
      nematic layers. The mechanism behind such shift is discussed under the light of
      propagation eigenmodes for a medium presenting circular and linear birefringence.
      The effects associated with the defect thickness are also analyzed. 

PMID- 24580248
TI  - Interaction of small spherical particles in confined cholesteric liquid crystals.
AB  - The theory of the elastic interaction of spherical colloidal particles immersed
      into a confined cholesteric liquid crystal is proposed. The case of weak
      anchoring on the particle surfaces is considered. We derive a general expression
      for the energy of the interaction between small spherical particles (with
      diameter much smaller than the cholesteric pitch) suspended in a cholesteric
      confined by two parallel planes. The resulting form of the interaction energy has
      a more complex spatial pattern and energy versus distance dependence than that in
      nematic colloids. The absence of translational symmetry related to helical
      periodicity and local nematic ordering in cholesteric liquid crystals manifest
      themselves in the complex nature of the interaction maps. 

PMID- 24580249
TI  - Dynamical heterogeneity in periodically deformed polymer glasses.
AB  - The dynamics of structural relaxation in a model polymer glass subject to
      spatially homogeneous, time-periodic shear deformation is investigated using
      molecular dynamics simulations. We study a coarse-grained bead-spring model of
      short polymer chains below the glass transition temperature. It is found that at
      small strain amplitudes, the segmental dynamics is nearly reversible over about
      10^{4} cycles, while at strain amplitudes above a few percent, polymer chains
      become fully relaxed after a hundred cycles. At the critical strain amplitude,
      the transition from slow to fast relaxation dynamics is associated with the
      largest number of dynamically correlated monomers as indicated by the peak value
      of the dynamical susceptibility. The analysis of individual monomer trajectories
      showed that mobile monomers tend to assist their neighbors to become mobile and
      aggregate into relatively compact transient clusters. 

PMID- 24580250
TI  - Mullins effect in a filled elastomer under uniaxial tension.
AB  - Modulus softening and permanent set in filled polymeric materials due to cyclic
      loading and unloading, commonly known as the Mullins effect, can have a
      significant impact on their use as support cushions. A quantitative analysis of
      such behavior is essential to ensure the effectiveness of such materials in long
      term deployment. In this work we combine existing ideas of filler-induced modulus
      enhancement, strain amplification, and irreversible deformation within a simple
      non-Gaussian constitutive model to quantitatively interpret recent measurements
      on a relevant PDMS-based elastomeric cushion. We find that the experimental
      stress-strain data is consistent with the picture that during stretching
      (loading) two effects take place simultaneously: (1) the physical constraints
      (entanglements) initially present in the polymer network get disentangled, thus
      leading to a gradual decrease in the effective cross-link density, and (2) the
      effective filler volume fraction gradually decreases with increasing strain due
      to the irreversible pulling out of an initially occluded volume of the soft
      polymer domain. 

PMID- 24580251
TI  - Critical phenomena and noise-induced phase transitions in neuronal networks.
AB  - We study numerically and analytically first- and second-order phase transitions
      in neuronal networks stimulated by shot noise (a flow of random spikes bombarding
      neurons). Using an exactly solvable cortical model of neuronal networks on
      classical random networks, we find critical phenomena accompanying the
      transitions and their dependence on the shot noise intensity. We show that a
      pattern of spontaneous neuronal activity near a critical point of a phase
      transition is a characteristic property that can be used to identify the
      bifurcation mechanism of the transition. We demonstrate that bursts and
      avalanches are precursors of a first-order phase transition, paroxysmal-like
      spikes of activity precede a second-order phase transition caused by a saddle
      node bifurcation, while irregular spindle oscillations represent spontaneous
      activity near a second-order phase transition caused by a supercritical Hopf
      bifurcation. Our most interesting result is the observation of the paroxysmal
      like spikes. We show that a paroxysmal-like spike is a single nonlinear event
      that appears instantly from a low background activity with a rapid onset, reaches
      a large amplitude, and ends up with an abrupt return to lower activity. These
      spikes are similar to single paroxysmal spikes and sharp waves observed in
      electroencephalographic (EEG) measurements. Our analysis shows that above the
      saddle-node bifurcation, sustained network oscillations appear with a large
      amplitude but a small frequency in contrast to network oscillations near the Hopf
      bifurcation that have a small amplitude but a large frequency. We discuss an
      amazing similarity between excitability of the cortical model stimulated by shot
      noise and excitability of the Morris-Lecar neuron stimulated by an applied
      current. 

PMID- 24580253
TI  - Membrane compression in tumbling and vacillating-breathing regimes for
      quasispherical vesicles.
AB  - We derive some analytical results of a well-known model for quasispherical
      vesicles in a linear shear flow at low deformability. Attention is focussed on
      the oscillatory regimes: the tumbling (TB) mode, vacillating-breathing (VB) mode,
      and the transition from vacillating-breathing to tumbling, depending on a control
      parameter Gamma. It is shown that, during the VB-to-TB transition (Gamma=1), the
      vesicle momentarily attains its maximal extension in the vorticity direction and
      transits through a circular profile in the shear plane for which the radius is
      exactly determined. In addition, we provide an explicit analytical expression for
      the effective membrane tension for different types of motions. We find a critical
      bending number below which the membrane undergoes compression at each instant and
      show that, during the VB-to-TB transition, a fourth-order membrane deformation is
      possible. 

PMID- 24580254
TI  - Circumferential gap propagation in an anisotropic elastic bacterial sacculus.
AB  - We have modeled stress concentration around small gaps in anisotropic elastic
      sheets, corresponding to the peptidoglycan sacculus of bacterial cells, under
      loading corresponding to the effects of turgor pressure in rod-shaped bacteria.
      We find that under normal conditions the stress concentration is insufficient to
      mechanically rupture bacteria, even for gaps up to a micron in length. We then
      explored the effects of stress-dependent smart autolysins, as hypothesized by A.
      L. Koch [ Adv. Microb. Physiol. 24 301 (1983); Res. Microbiol. 141 529 (1990)].
      We show that the measured anisotropic elasticity of the peptidoglycan (PG)
      sacculus can lead to stable circumferential propagation of small gaps in the
      sacculus. This is consistent with the recent observation of circumferential
      propagation of PG-associated MreB patches in rod-shaped bacteria. We also find a
      bistable regime of both circumferential and axial gap propagation, which agrees
      with behavior reported in cytoskeletal mutants of B. subtilis. We conclude that
      the elastic anisotropies of a bacterial sacculus, as characterized
      experimentally, may be relevant for maintaining rod-shaped bacterial growth. 

PMID- 24580252
TI  - Statistical mechanical model of coupled transcription from multiple promoters due
      to transcription factor titration.
AB  - Transcription factors (TFs) with regulatory action at multiple promoter targets
      is the rule rather than the exception, with examples ranging from the cAMP
      receptor protein (CRP) in E. coli that regulates hundreds of different genes
      simultaneously to situations involving multiple copies of the same gene, such as
      plasmids, retrotransposons, or highly replicated viral DNA. When the number of
      TFs heavily exceeds the number of binding sites, TF binding to each promoter can
      be regarded as independent. However, when the number of TF molecules is
      comparable to the number of binding sites, TF titration will result in
      correlation ("promoter entanglement") between transcription of different genes.
      We develop a statistical mechanical model which takes the TF titration effect
      into account and use it to predict both the level of gene expression for a
      general set of promoters and the resulting correlation in transcription rates of
      different genes. Our results show that the TF titration effect could be important
      for understanding gene expression in many regulatory settings. 

PMID- 24580255
TI  - Characterization of the low-temperature properties of a simplified protein model.
AB  - Prompted by results that showed that a simple protein model, the frustrated Go
      model, appears to exhibit a transition reminiscent of the protein dynamical
      transition, we examine the validity of this model to describe the low-temperature
      properties of proteins. First, we examine equilibrium fluctuations. We calculate
      its incoherent neutron-scattering structure factor and show that it can be well
      described by a theory using the one-phonon approximation. By performing an
      inherent structure analysis, we assess the transitions among energy states at low
      temperatures. Then, we examine nonequilibrium fluctuations after a sudden cooling
      of the protein. We investigate the violation of the fluctuation-dissipation
      theorem in order to analyze the protein glass transition. We find that the
      effective temperature of the quenched protein deviates from the temperature of
      the thermostat, however it relaxes towards the actual temperature with an
      Arrhenius behavior as the waiting time increases. These results of the
      equilibrium and nonequilibrium studies converge to the conclusion that the
      apparent dynamical transition of this coarse-grained model cannot be attributed
      to a glassy behavior. 

PMID- 24580256
TI  - Run-and-tumble dynamics in a crowded environment: persistent exclusion process
      for swimmers.
AB  - The effect of crowding on the run-and-tumble dynamics of swimmers such as
      bacteria is studied using a discrete lattice model of mutually excluding
      particles that move with constant velocity along a direction that is randomized
      at a rate alpha. In stationary state, the system is found to break into dense
      clusters in which particles are trapped or stopped from moving. The
      characteristic size of these clusters predominantly scales as alpha(-0.5) in both
      one and two dimensions. For a range of densities, due to cooperative effects, the
      stopping time scales as T(1d)(0.85) and as T(2d)(0.8), where T(d) is the
      diffusive time associated with the motion of cluster boundaries. Our findings
      might be helpful in understanding the early stages of biofilm formation.

PMID- 24580257
TI  - Creation and regulation of ion channels across reconstituted phospholipid
      bilayers generated by streptavidin-linked magnetite nanoparticles.
AB  - In this work, we explore the nature of ion-channel-like conductance fluctuations
      across a reconstituted phospholipid bilayer due to insertion of ~100 nm sized,
      streptavidin-linked magnetite nanoparticles under static magnetic fields (SMFs).
      For a fixed bias voltage, the frequency of current bursts increases with the
      application of SMFs. Apart from a closed conductance state G(0) (<=14 pS), we
      identify four major conductance states, with the lowest conductance level (G(1))
      being ~126 pS. The number of channel events at G(1) is found to be nearly doubled
      (as compared to G(0)) at a magnetic field of 70 G. The higher-order open states
      (e.g., 3G(1), 5G(1)) are generally observable at larger values of biasing voltage
      and magnetic field. When the SMF of 145 G is applied, the multiconductance states
      are resolved distinctly and are assigned to the simultaneous opening and closing
      of several independent states. The origin of the current bursts is due to the
      instantaneous mechanical actuation of streptavidin-linked MNP chains across the
      phospholipid bilayer. The voltage-controlled, magnetogated ion channels are
      promising for diagnoses and therapeutic applications of excitable membranes and
      other biological systems.

PMID- 24580258
TI  - Power-stroke-driven actomyosin contractility.
AB  - In ratchet-based models describing actomyosin contraction the activity is usually
      associated with actin binding potential while the power-stroke mechanism,
      residing inside myosin heads, is viewed as passive. To show that contraction can
      be propelled directly through a conformational change, we propose an alternative
      model where the power stroke is the only active mechanism. The asymmetry,
      ensuring directional motion, resides in steric interaction between the externally
      driven power-stroke element and the passive nonpolar actin filament. The proposed
      model can reproduce all four discrete states of the minimal actomyosin catalytic
      cycle even though it is formulated in terms of continuous Langevin dynamics. We
      build a conceptual bridge between processive and nonprocessive molecular motors
      by demonstrating that not only the former but also the latter can use structural
      transformation as the main driving force. 

PMID- 24580259
TI  - Maximum likelihood estimators for truncated and censored power-law distributions
      show how neuronal avalanches may be misevaluated.
AB  - The coordination of activity amongst populations of neurons in the brain is
      critical to cognition and behavior. One form of coordinated activity that has
      been widely studied in recent years is the so-called neuronal avalanche, whereby
      ongoing bursts of activity follow a power-law distribution. Avalanches that
      follow a power law are not unique to neuroscience, but arise in a broad range of
      natural systems, including earthquakes, magnetic fields, biological extinctions,
      fluid dynamics, and superconductors. Here, we show that common techniques that
      estimate this distribution fail to take into account important characteristics of
      the data and may lead to a sizable misestimation of the slope of power laws. We
      develop an alternative series of maximum likelihood estimators for discrete,
      continuous, bounded, and censored data. Using numerical simulations, we show that
      these estimators lead to accurate evaluations of power-law distributions,
      improving on common approaches. Next, we apply these estimators to recordings of
      in vitro rat neocortical activity. We show that different estimators lead to
      marked discrepancies in the evaluation of power-law distributions. These results
      call into question a broad range of findings that may misestimate the slope of
      power laws by failing to take into account key aspects of the observed data. 

PMID- 24580260
TI  - Anomalous fluctuation scaling laws in stochastic enzyme kinetics: increase of
      noise strength with the mean concentration.
AB  - It is commonly thought that if a rate constant is perturbed such that the
      intracellular concentration of a certain species increases, then the fluctuations
      in the concentration will correspondingly decrease in strength. We here test
      whether this conventional wisdom generally holds true. We study the dependence of
      the noise strength (the coefficient of variation) in protein concentrations as a
      function of the mean protein concentration for a system in which protein is
      transported in and out of an intracellular compartment and it is catalyzed into a
      product by a multisubunit enzyme inside the compartment. The mean protein
      concentration is varied through perturbation of one of the rate constants. For
      low protein concentrations, the noise strength scales as [P]-1/2, where [P] is
      the mean concentration; this is the conventional fluctuation scaling law.
      However, we show that over a wide range of physiological concentrations, there
      are manifest anomalous fluctuation scaling laws proportional to [P]0 and [P](N
      1)/2, where N is the number of binding sites of the multisubunit enzyme. These
      laws are particularly conspicuous when the rate of protein import into the
      compartment is much larger than its export rate out of the compartment and when
      the enzyme exhibits positive cooperativity. The results imply that over a certain
      range of physiological concentrations, noise strength remains the same or
      increases with the mean protein concentration. This contradicts the popularly
      held notion that noise strength decreases with increasing concentration and
      suggests that noise can be important even when the number of molecules is large. 

PMID- 24580261
TI  - Spiral and never-settling patterns in active systems.
AB  - We present a combined numerical and analytical study of pattern formation in an
      active system where particles align, possess a density-dependent motility, and
      are subject to a logistic reaction. The model can describe suspensions of
      reproducing bacteria, as well as polymerizing actomyosin gels in vitro or in
      vivo. In the disordered phase, we find that motility suppression and growth
      compete to yield stable or blinking patterns, which, when dense enough, acquire
      internal orientational ordering to give asters or spirals. We predict these may
      be observed within chemotactic aggregates in bacterial fluids. In the ordered
      phase, the reaction term leads to previously unobserved never-settling patterns
      which can provide a simple framework to understand the formation of motile and
      spiral patterns in intracellular actin systems. 

PMID- 24580262
TI  - Nonequilibrium stochastic model for tRNA binding time statistics.
AB  - Protein translation is one of the most important processes in cell life, but
      despite being well-understood biochemically, the implications of its intrinsic
      stochastic nature have not been fully elucidated. In this paper we develop a
      microscopic and stochastic model which describes a crucial step in protein
      translation, namely the binding of the tRNA to the ribosome. Our model explicitly
      takes into consideration tRNA recharging dynamics, spatial inhomogeneity, and
      stochastic fluctuations in the number of charged tRNAs around the ribosome. By
      analyzing this nonequilibrium system we are able to derive the statistical
      distribution of the times needed by the tRNAs to bind to the ribosome, and to
      show that it deviates from an exponential due to the coupling between the
      fluctuations of charged and uncharged populations of tRNA. 

PMID- 24580263
TI  - Alternative-splicing-mediated gene expression.
AB  - Alternative splicing (AS) is a fundamental process during gene expression and has
      been found to be ubiquitous in eukaryotes. However, how AS impacts gene
      expression levels both quantitatively and qualitatively remains to be fully
      explored. Here, we analyze two common models of gene expression, each
      incorporating a simple splice mechanism that a pre-mRNA is spliced into two
      mature mRNA isoforms in a probabilistic manner. In the constitutive expression
      case, we show that the steady-state molecular numbers of two mature mRNA isoforms
      follow mutually independent Poisson distributions. In the bursting expression
      case, we demonstrate that the tail decay of the steady-state distribution for
      both mature mRNA isoforms that in general are not mutually independent can be
      characterized by the product of mean burst size and splicing probability. In both
      cases, we find that AS can efficiently modulate both the variability (measured by
      variance) and the noise level of the total mature mRNA, and in particular, the
      latter is always lower than the noise level of the pre-mRNA, implying that AS
      always reduces the noise. These results altogether reveal that AS is a mechanism
      of efficiently controlling the gene expression noise. 

PMID- 24580264
TI  - Elastic constants in orthorhombic hen egg-white lysozyme crystals.
AB  - The ultrasonic sound velocities of cross-linked orthorhombic hen egg-white
      lysozyme (HEWL) crystals, including a large amount of water in the crystal, were
      measured using an ultrasonic pulse-echo method. As a result, seven elastic
      constants of orthorhombic crystals were observed to be C11 = 5.24 GPa, C22 = 4.87
      GPa, C12 = 4.02 GPa, C33 = 5.23 GPa, C44 = 0.30 GPa, C55 = 0.40 GPa, and C66 =
      0.43 GPa, respectively. However, C13 and C23 could not be observed because the
      suitable crystal planes could not be cut from bulk crystals. We conclude that the
      observed elastic constants of the cross-linked crystals are coincident with those
      of the intrinsic crystals without cross-linking. Moreover, the characteristics of
      the elastic constants in orthorhombic HEWL crystals are due to the fact that the
      shear elastic constants, C44, C55, and C66, are softer than in tetragonal
      crystals. That is, the shear components, C44, C55, and C66, are one half of those
      of the tetragonal crystals.

PMID- 24580265
TI  - Distribution of population-averaged observables in stochastic gene expression.
AB  - Observation of phenotypic diversity in a population of genetically identical
      cells is often linked to the stochastic nature of chemical reactions involved in
      gene regulatory networks. We investigate the distribution of population-averaged
      gene expression levels as a function of population, or sample, size for several
      stochastic gene expression models to find out to what extent population-averaged
      quantities reflect the underlying mechanism of gene expression. We consider three
      basic gene regulation networks corresponding to transcription with and without
      gene state switching and translation. Using analytical expressions for the
      probability generating function of observables and large deviation theory, we
      calculate the distribution and first two moments of the population-averaged mRNA
      and protein levels as a function of model parameters, population size, and number
      of measurements contained in a data set. We validate our results using stochastic
      simulations also report exact results on the asymptotic properties of population
      averages which show qualitative differences among different models. 

PMID- 24580266
TI  - Quantifying control effort of biological and technical movements: an information
      entropy-based approach.
AB  - In biomechanics and biorobotics, muscles are often associated with reduced
      movement control effort and simplified control compared to technical actuators.
      This is based on evidence that the nonlinear muscle properties positively
      influence movement control. It is, however, open how to quantify the simplicity
      aspect of control effort and compare it between systems. Physical measures, such
      as energy consumption, stability, or jerk, have already been applied to compare
      biological and technical systems. Here a physical measure of control effort based
      on information entropy is presented. The idea is that control is simpler if a
      specific movement is generated with less processed sensor information, depending
      on the control scheme and the physical properties of the systems being compared.
      By calculating the Shannon information entropy of all sensor signals required for
      control, an information cost function can be formulated allowing the comparison
      of models of biological and technical control systems. Exemplarily applied to
      (bio-)mechanical models of hopping, the method reveals that the required
      information for generating hopping with a muscle driven by a simple reflex
      control scheme is only I=32 bits versus I=660 bits with a DC motor and a
      proportional differential controller. This approach to quantifying control effort
      captures the simplicity of a control scheme and can be used to compare completely
      different actuators and control approaches.

PMID- 24580267
TI  - Optimizing snake locomotion on an inclined plane.
AB  - We develop a model to study the locomotion of snakes on inclined planes. We
      determine numerically which snake motions are optimal for two retrograde
      traveling-wave body shapes, triangular and sinusoidal waves, across a wide range
      of frictional parameters and incline angles. In the regime of large transverse
      friction coefficients, we find power-law scalings for the optimal wave amplitudes
      and corresponding costs of locomotion. We give an asymptotic analysis to show
      that the optimal snake motions are traveling waves with amplitudes given by the
      same scaling laws found in the numerics. 

PMID- 24580268
TI  - Flocking with minimal cooperativity: the panic model.
AB  - We present a two-dimensional lattice model of self-propelled spins that can
      change direction only upon collision with another spin. We show that even with
      ballistic motion and minimal cooperativity, these spins display robust flocking
      behavior at nearly all densities, forming long bands of stripes. The structural
      transition in this system is not a thermodynamic phase transition, but it can
      still be characterized by an order parameter, and we demonstrate that if this
      parameter is studied as a dynamical variable rather than a steady-state
      observable, we can extract a detailed picture of how the flocking mechanism
      varies with density. 

PMID- 24580270
TI  - Self-organized vortices of circling self-propelled particles and curved active
      flagella.
AB  - Self-propelled pointlike particles move along circular trajectories when their
      translocation velocity is constant and the angular velocity related to their
      orientation vector is also constant. We investigate the collective behavior of
      ensembles of such circle swimmers by Brownian dynamics simulations. If the
      particles interact via a "velocity-trajectory coordination" rule within
      neighboring particles, a self-organized vortex pattern emerges. This vortex
      pattern is characterized by its particle-density correlation function Grho, the
      density correlation function Gc of trajectory centers, and an order parameter S
      representing the degree of the aggregation of the particles. Here we
      systematically vary the system parameters, such as the particle density and the
      interaction range, in order to reveal the transition of the system from a light
      vortex-dominated to heavy-vortex-dominated state, where vortices contain mainly a
      single and many self-propelled particles, respectively. We also study a
      semidilute solution of curved, sinusoidal-beating flagella, as an example of
      circling self-propelled particles with explicit propulsion mechanism and excluded
      volume interactions. Our simulation results are compared with previous
      experimental results for the vortices in sea-urchin sperm solutions near a wall.
      The properties of the vortices in simulations and experiments are found to agree
      quantitatively. 

PMID- 24580271
TI  - Mobility-dependent selection of competing strategy associations.
AB  - Standard models of population dynamics focus on the interaction, survival, and
      extinction of the competing species individually. Real ecological systems,
      however, are characterized by an abundance of species (or strategies, in the
      terminology of evolutionary-game theory) that form intricate, complex interaction
      networks. The description of the ensuing dynamics may be aided by studying
      associations of certain strategies rather than individual ones. Here we show how
      such a higher-level description can bear fruitful insight. Motivated from
      different strains of colicinogenic Escherichia coli bacteria, we investigate a
      four-strategy system which contains a three-strategy cycle and a neutral alliance
      of two strategies. We find that the stochastic, spatial model exhibits a mobility
      dependent selection of either the three-strategy cycle or of the neutral pair. We
      analyze this intriguing phenomenon numerically and analytically. 

PMID- 24580272
TI  - Output-input ratio in thermally fluctuating biomolecular machines.
AB  - Biological molecular machines are proteins that operate under isothermal
      conditions and hence are referred to as free energy transducers. They can be
      formally considered as enzymes that simultaneously catalyze two chemical
      reactions: the free energy-donating (input) reaction and the free energy
      accepting (output) one. Most if not all biologically active proteins display a
      slow stochastic dynamics of transitions between a variety of conformational
      substates composing their native state. This makes the description of the
      enzymatic reaction kinetics in terms of conventional rate constants insufficient.
      In the steady state, upon taking advantage of the assumption that each reaction
      proceeds through a single pair (the gate) of transition conformational substates
      of the enzyme-substrates complex, the degree of coupling between the output and
      the input reaction fluxes has been expressed in terms of the mean first-passage
      times on a conformational transition network between the distinguished substates.
      The theory is confronted with the results of random-walk simulations on the five
      dimensional hypercube. The formal proof is given that, for single input and
      output gates, the output-input degree of coupling cannot exceed unity. As some
      experiments suggest such exceeding, looking for the conditions for increasing the
      degree of coupling value over unity challenges the theory. Performed simulations
      of random walks on several model networks involving more extended gates indicate
      that the case of the degree of coupling value higher than 1 is realized in a
      natural way on critical branching trees extended by long-range shortcuts. Such
      networks are scale-free and display the property of the small world. For short
      range shortcuts, the networks are scale-free and fractal, representing a
      reasonable model for biomolecular machines displaying tight coupling, i.e., the
      degree of coupling equal exactly to unity. A hypothesis is stated that the
      protein conformational transition networks, as just as higher-level biological
      networks, the protein interaction network, and the metabolic network, have
      evolved in the process of self-organized criticality. 

PMID- 24580269
TI  - Phase transitions in pancreatic islet cellular networks and implications for type
      1 diabetes.
AB  - In many aspects the onset of a chronic disease resembles a phase transition in a
      complex dynamic system: Quantitative changes accumulate largely unnoticed until a
      critical threshold is reached, which causes abrupt qualitative changes of the
      system. In this study we examine a special case, the onset of type-1 diabetes
      (T1D), a disease that results from loss of the insulin-producing pancreatic islet
      beta cells. Within each islet, the beta cells are electrically coupled to each
      other via gap-junctional channels. This intercellular coupling enables the beta
      cells to synchronize their insulin release, thereby generating the multiscale
      temporal rhythms in blood insulin that are critical to maintaining blood glucose
      homeostasis. Using percolation theory we show how normal islet function is
      intrinsically linked to network connectivity. In particular, the critical amount
      of beta-cell death at which the islet cellular network loses site percolation is
      consistent with laboratory and clinical observations of the threshold loss of
      beta cells that causes islet functional failure. In addition, numerical
      simulations confirm that the islet cellular network needs to be percolated for
      beta cells to synchronize. Furthermore, the interplay between site percolation
      and bond strength predicts the existence of a transient phase of islet functional
      recovery after onset of T1D and introduction of treatment, potentially explaining
      the honeymoon phenomenon. Based on these results, we hypothesize that the onset
      of T1D may be the result of a phase transition of the islet beta-cell network. 

PMID- 24580273
TI  - Side-chain-side-chain interactions and stability of the helical state.
AB  - Understanding the driving forces that lead to the stability of the secondary
      motifs found in proteins, namely alpha-helix and beta-sheet, is a major goal in
      structural biology. The thermodynamic stability of these repetitive units is a
      result of a delicate balance between many factors, which in addition to the
      peptide chain involves also the solvent. Despite the fact that the backbones of
      all amino acids are the same (except of that of proline), there are large
      differences in the propensity of the different amino acids to promote the helical
      structure. In this paper, we investigate by explicit-solvent molecular dynamics
      simulations the role of the side chains (modeled as coarse-grained single sites)
      in stabilizing alpha helices in an aqueous solution. Our model systems include
      four (six-mer-nine-mer) peptide lengths in which the magnitude of the effective
      attraction between the side chains is systematically increased. We find that
      these interactions between the side chains can induce (for the nine-mer almost
      completely) a transition from a coil to a helical state. This transition is found
      to be characterized by three states in which the intermediate state is a
      partially folded alpha-helical conformation. In the absence of any interactions
      between the side chains the free energy change for helix formation has a small
      positive value indicating that favorable contributions from the side chains are
      necessary to stabilize the helical conformation. Thus, the helix-coil transition
      is controlled by the effective potentials between the side-chain residues and the
      magnitude of the required attraction per residue, which is on the order of the
      thermal energy, reduces with the length of the peptide. Surprisingly, the plots
      of the population of the helical state (or the change in the free energy for
      helix formation) as a function of the total effective interactions between the
      side chains in the helical state for all peptide lengths fall on the same curve. 

PMID- 24580274
TI  - Two-time-scale population evolution on a singular landscape.
AB  - Under the effect of strong genetic drift, it is highly probable to observe gene
      fixation or gene loss in a population, shown by singular peaks on a potential
      landscape. The genetic drift-induced noise gives rise to two-time-scale diffusion
      dynamics on the bipeaked landscape. We find that the logarithmically divergent
      (singular) peaks do not necessarily imply infinite escape times or biological
      fixations by iterating the Wright-Fisher model and approximating the average
      escape time. Our analytical results under weak mutation and weak selection extend
      Kramers's escape time formula to models with B (Beta) function-like equilibrium
      distributions and overcome constraints in previous methods. The constructed
      landscape provides a coherent description for the bistable system, supports the
      quantitative analysis of bipeaked dynamics, and generates mathematical insights
      for understanding the boundary behaviors of the diffusion model. 

PMID- 24580275
TI  - Resiliently evolving supply-demand networks.
AB  - The ability to design a transport network such that commodities are brought from
      suppliers to consumers in a steady, optimal, and stable way is of great
      importance for distribution systems nowadays. In this work, by using the circuit
      laws of Kirchhoff and Ohm, we provide the exact capacities of the edges that an
      optimal supply-demand network should have to operate stably under perturbations,
      i.e., without overloading. The perturbations we consider are the evolution of the
      connecting topology, the decentralization of hub sources or sinks, and the
      intermittence of supplier and consumer characteristics. We analyze these
      conditions and the impact of our results, both on the current United Kingdom
      power-grid structure and on numerically generated evolving archetypal network
      topologies. 

PMID- 24580276
TI  - Nonparametric resampling of random walks for spectral network clustering.
AB  - Parametric resampling schemes have been recently introduced in complex network
      analysis with the aim of assessing the statistical significance of graph
      clustering and the robustness of community partitions. We propose here a method
      to replicate structural features of complex networks based on the non-parametric
      resampling of the transition matrix associated with an unbiased random walk on
      the graph. We test this bootstrapping technique on synthetic and real-world
      modular networks and we show that the ensemble of replicates obtained through
      resampling can be used to improve the performance of standard spectral algorithms
      for community detection. 

PMID- 24580277
TI  - Characteristic times of biased random walks on complex networks.
AB  - We consider degree-biased random walkers whose probability to move from a node to
      one of its neighbors of degree k is proportional to k(alpha), where alpha is a
      tuning parameter. We study both numerically and analytically three types of
      characteristic times, namely (i) the time the walker needs to come back to the
      starting node, (ii) the time it takes to visit a given node for the first time,
      and (iii) the time it takes to visit all the nodes of the network. We consider a
      large data set of real-world networks and we show that the value of alpha which
      minimizes the three characteristic times differs from the value alpha(min)=-1
      analytically found for uncorrelated networks in the mean-field approximation. In
      addition to this, we found that assortative networks have preferentially a value
      of alpha(min) in the range [-1,-0.5], while disassortative networks have
      alpha(min) in the range [-0.5,0]. We derive an analytical relation between the
      degree correlation exponent nu and the optimal bias value alpha(min), which works
      well for real-world assortative networks. When only local information is
      available, degree-biased random walks can guarantee smaller characteristic times
      than the classical unbiased random walks by means of an appropriate tuning of the
      motion bias.

PMID- 24580278
TI  - Efficient Monte Carlo and greedy heuristic for the inference of stochastic block
      models.
AB  - We present an efficient algorithm for the inference of stochastic block models in
      large networks. The algorithm can be used as an optimized Markov chain Monte
      Carlo (MCMC) method, with a fast mixing time and a much reduced susceptibility to
      getting trapped in metastable states, or as a greedy agglomerative heuristic,
      with an almost linear O(Nln2N) complexity, where N is the number of nodes in the
      network, independent of the number of blocks being inferred. We show that the
      heuristic is capable of delivering results which are indistinguishable from the
      more exact and numerically expensive MCMC method in many artificial and empirical
      networks, despite being much faster. The method is entirely unbiased towards any
      specific mixing pattern, and in particular it does not favor assortative
      community structures. 

PMID- 24580279
TI  - Exploring the evolution of London's street network in the information space: a
      dual approach.
AB  - We study the growth of London's street network in its dual representation, as the
      city has evolved over the past 224 years. The dual representation of a planar
      graph is a content-based network, where each node is a set of edges of the planar
      graph and represents a transportation unit in the so-called information space,
      i.e., the space where information is handled in order to navigate through the
      city. First, we discuss a novel hybrid technique to extract dual graphs from
      planar graphs, called the hierarchical intersection continuity negotiation
      principle. Then we show that the growth of the network can be analytically
      described by logistic laws and that the topological properties of the network are
      governed by robust log-normal distributions characterizing the network's
      connectivity and small-world properties that are consistent over time. Moreover,
      we find that the double-Pareto-like distributions for the connectivity emerge for
      major roads and can be modeled via a stochastic content-based network model using
      simple space-filling principles. 

PMID- 24580280
TI  - Emergence of overlap in ensembles of spatial multiplexes and statistical
      mechanics of spatial interacting network ensembles.
AB  - Spatial networks range from the brain networks, to transportation networks and
      infrastructures. Recently interacting and multiplex networks are attracting great
      attention because their dynamics and robustness cannot be understood without
      treating at the same time several networks. Here we present maximal entropy
      ensembles of spatial multiplex and spatial interacting networks that can be used
      in order to model spatial multilayer network structures and to build null models
      of real data sets. We show that spatial multiplexes naturally develop a
      significant overlap of the links, a noticeable property of many multiplexes that
      can affect significantly the dynamics taking place on them. Additionally, we
      characterize ensembles of spatial interacting networks and we analyze the
      structure of interacting airport and railway networks in India, showing the
      effect of space in determining the link probability. 

PMID- 24580281
TI  - Bottom-up model of self-organized criticality on networks.
AB  - The Bak-Tang-Wiesenfeld (BTW) sandpile process is an archetypal, stylized model
      of complex systems with a critical point as an attractor of their dynamics. This
      phenomenon, called self-organized criticality, appears to occur ubiquitously in
      both nature and technology. Initially introduced on the two-dimensional lattice,
      the BTW process has been studied on network structures with great analytical
      successes in the estimation of macroscopic quantities, such as the exponents of
      asymptotically power-law distributions. In this article, we take a microscopic
      perspective and study the inner workings of the process through both numerical
      and rigorous analysis. Our simulations reveal fundamental flaws in the
      assumptions of past phenomenological models, the same models that allowed
      accurate macroscopic predictions; we mathematically justify why universality may
      explain these past successes. Next, starting from scratch, we obtain microscopic
      understanding that enables mechanistic models; such models can, for example,
      distinguish a cascade's area from its size. In the special case of a 3-regular
      network, we use self-consistency arguments to obtain a zero-parameter mechanistic
      (bottom-up) approximation that reproduces nontrivial correlations observed in
      simulations and that allows the study of the BTW process on networks in regimes
      otherwise prohibitively costly to investigate. We then generalize some of these
      results to configuration model networks and explain how one could continue the
      generalization. The numerous tools and methods presented herein are known to
      enable studying the effects of controlling the BTW process and other self
      organizing systems. More broadly, our use of multitype branching processes to
      capture information bouncing back and forth in a network could inspire analogous
      models of systems in which consequences spread in a bidirectional fashion. 

PMID- 24580282
TI  - Cavity-based robustness analysis of interdependent networks: influences of
      intranetwork and internetwork degree-degree correlations.
AB  - We develop a methodology for analyzing the percolation phenomena of two mutually
      coupled (interdependent) networks based on the cavity method of statistical
      mechanics. In particular, we take into account the influence of degree-degree
      correlations inside and between the networks on the network robustness against
      targeted (random degree-dependent) attacks and random failures. We show that the
      developed methodology is reduced to the well-known generating function formalism
      in the absence of degree-degree correlations. The validity of the developed
      methodology is confirmed by a comparison with the results of numerical
      experiments. Our analytical results indicate that the robustness of the
      interdependent networks depends on both the intranetwork and internetwork degree
      degree correlations in a nontrivial way for both cases of random failures and
      targeted attacks. 

PMID- 24580283
TI  - Dynamics of interacting information waves in networks.
AB  - To better understand the inner workings of information spreading, network
      researchers often use simple models to capture the spreading dynamics. But most
      models only highlight the effect of local interactions on the global spreading of
      a single information wave, and ignore the effects of interactions between
      multiple waves. Here we take into account the effect of multiple interacting
      waves by using an agent-based model in which the interaction between information
      waves is based on their novelty. We analyzed the global effects of such
      interactions and found that information that actually reaches nodes reaches them
      faster. This effect is caused by selection between information waves: lagging
      waves die out and only leading waves survive. As a result, and in contrast to
      models with noninteracting information dynamics, the access to information decays
      with the distance from the source. Moreover, when we analyzed the model on
      various synthetic and real spatial road networks, we found that the decay rate
      also depends on the path redundancy and the effective dimension of the system. In
      general, the decay of the information wave frequency as a function of distance
      from the source follows a power-law distribution with an exponent between -0.2
      for a two-dimensional system with high path redundancy and -0.5 for a tree-like
      system with no path redundancy. We found that the real spatial networks provide
      an infrastructure for information spreading that lies in between these two
      extremes. Finally, to better understand the mechanics behind the scaling results,
      we provide analytical calculations of the scaling for a one-dimensional system. 

PMID- 24580284
TI  - Nature of synchronization transitions in random networks of coupled oscillators.
AB  - We consider a system of phase oscillators with random intrinsic frequencies
      coupled through sparse random networks and investigate how the connectivity
      disorder affects the nature of collective synchronization transitions. Various
      distribution types of intrinsic frequencies are considered: uniform, unimodal,
      and bimodal distribution. We employ a heterogeneous mean-field approximation
      based on the annealed networks and also perform numerical simulations on the
      quenched Erdos-Renyi networks. We find that the connectivity disorder drastically
      changes the nature of the synchronization transitions. In particular, the
      quenched randomness completely wipes away the diversity of the transition nature,
      and only a continuous transition appears with the same mean-field exponent for
      all types of frequency distributions. The physical origin of this unexpected
      result is discussed. 

PMID- 24580285
TI  - Potential for the dynamics of pedestrians in a socially interacting group.
AB  - We introduce a simple potential to describe the dynamics of the relative motion
      of two pedestrians socially interacting in a walking group. We show that the
      proposed potential, based on basic empirical observations and theoretical
      considerations, can qualitatively describe the statistical properties of
      pedestrian behavior. In detail, we show that the two-dimensional probability
      distribution of the relative distance is determined by the proposed potential
      through a Boltzmann distribution. After calibrating the parameters of the model
      on the two-pedestrian group data, we apply the model to three-pedestrian groups,
      showing that it describes qualitatively and quantitatively well their behavior.
      In particular, the model predicts that three-pedestrian groups walk in a V-shaped
      formation and provides accurate values for the position of the three pedestrians.
      Furthermore, the model correctly predicts the average walking velocity of three
      person groups based on the velocity of two-person ones. Possible extensions to
      larger groups, along with alternative explanations of the social dynamics that
      may be implied by our model, are discussed at the end of the paper. 

PMID- 24580286
TI  - Algebraic approach to small-world network models.
AB  - We introduce an analytic model for directed Watts-Strogatz small-world graphs and
      deduce an algebraic expression of its defining adjacency matrix. The latter is
      then used to calculate the small-world digraph's asymmetry index and clustering
      coefficient in an analytically exact fashion, valid nonasymptotically for all
      graph sizes. The proposed approach is general and can be applied to all
      algebraically well-defined graph-theoretical measures, thus allowing for an
      analytical investigation of finite-size small-world graphs. 

PMID- 24580287
TI  - Vulnerability of networks: fractional percolation on random graphs.
AB  - We present a theoretical framework for understanding nonbinary, nonindependent
      percolation on networks with general degree distributions. The model incorporates
      a partially functional (PF) state of nodes so that both intensity and extensity
      of error are characterized. Two connected nodes in a PF state cannot sustain the
      load and therefore break their link. We give exact solutions for the percolation
      threshold, the fraction of giant cluster, and the mean size of small clusters.
      The robustness-fragility transition point for scale-free networks with a degree
      distribution pk ? k-alpha is identified to be alpha=3. The analysis reveals that
      scale-free networks are vulnerable to targeted attack at hubs: a more complete
      picture of their Achilles' heel turns out to be not only the hubs themselves but
      also the edges linking them together.

PMID- 24580288
TI  - Community analysis in directed networks: in-, out-, and pseudocommunities.
AB  - When analyzing important classes of complex interconnected systems, link
      directionality can hardly be neglected if a precise and effective picture of the
      structure and function of the system is needed. If community analysis is
      performed, the notion of "community" itself is called into question, since the
      property of having a comparatively looser external connectivity could refer to
      the inbound or outbound links only or to both categories. In this paper, we
      introduce the notions of in-, out-, and in-/out-community in order to correctly
      classify the directedness of the interaction of a subnetwork with the rest of the
      system. Furthermore, we extend the scope of community analysis by introducing the
      notions of in-, out-, and in-/out-pseudocommunity. They are subnetworks having
      strong internal connectivity but also important interactions with the rest of the
      system, the latter taking place by means of a minority of its nodes only. The
      various types of (pseudo-)communities are qualified and distinguished by a
      suitable set of indicators and, on a given network, they can be discovered by
      using a "local" searching algorithm. The application to a broad set of benchmark
      networks and real-world examples proves that the proposed approach is able to
      effectively disclose the different types of structures above defined and to
      usefully classify the directionality of their interactions with the rest of the
      system. 

PMID- 24580289
TI  - Rubik's cube: an energy perspective.
AB  - What if we played the Rubik's cube game by simple intuition? We would rotate the
      cube, probably in the hope of getting a more organized pattern in each next step.
      Yet frustration occurs easily, and we soon find ourselves trapped as the game
      progresses no further. Played in this completely strategy-less style, the entire
      problem of the Rubik's cube game can be compared to that of complex chemical
      reactions such as protein folding, only with less guidance in the searching
      process. In this work we look into this random-searching process by means of
      thermodynamics and compare the game's dynamics with that of a faithful stochastic
      model constructed from the statistical energy landscape theory (SELT). This
      comparison reveals the peculiar nature of SELT, which relies on the random energy
      approximation and often chops up energy correlations among nearby configurations.
      Our observation provides a general insight for the use of SELT in the studies of
      these frustrated systems. 

PMID- 24580290
TI  - Failure mechanisms of load-sharing complex systems.
AB  - We investigate the failure mechanisms of load-sharing complex systems. The system
      is composed of multiple nodes or components whose failures are determined based
      on the interaction of their respective strengths and loads (or capacity and
      demand, respectively) as well as the ability of a component to share its load
      with its neighbors when needed. We focus on two distinct mechanisms to model the
      interaction between components' strengths and loads. The failure mechanisms of
      these two models demonstrate temporal scaling phenomena, phase transitions, and
      multiple distinct failure modes excited by extremal dynamics. For critical ranges
      of parameters the models demonstrate power-law and exponential failure patterns.
      We identify the similarities and differences between the two mechanisms and the
      implications of our results for the failure mechanisms of complex systems in the
      real world. 

PMID- 24580291
TI  - Propagation failure for a front between stable states in a system with
      subdiffusion.
AB  - The propagation of subdiffusion-reaction fronts is studied in the framework of a
      model recently suggested by Fedotov [ Phys. Rev. E 81 011117 (2010)]. An exactly
      solvable model with a piecewise linear reaction function is considered. A drastic
      difference between the cases of normal diffusion and subdiffusion has been
      revealed. While in the case of normal diffusion, a traveling wave solution
      between two locally stable phases always exists, and is unique, in the case of
      the subdiffusion such solutions do not exist. The numerical simulation shows that
      the velocity of the front decreases with time according to a power law. The only
      kind of fronts moving with a constant velocity are waves which propagate solely
      due to the reaction, with a vanishing subdiffusive flux. 

PMID- 24580292
TI  - First-harmonic approximation in nonlinear chirped-driven oscillators.
AB  - Nonlinear classical oscillators can be excited to high energies by a weak driving
      field provided the drive frequency is properly chirped. This process is known as
      autoresonance (AR). We find that for a large class of oscillators, it is
      sufficient to consider only the first harmonic of the motion when studying AR,
      even when the dynamics is highly nonlinear. The first harmonic approximation is
      also used to relate AR in an asymmetric potential to AR in a "frequency
      equivalent" symmetric potential and to study the autoresonance breakdown
      phenomenon. 

PMID- 24580293
TI  - Spatial localization in heterogeneous systems.
AB  - We study spatial localization in the generalized Swift-Hohenberg equation with
      either quadratic-cubic or cubic-quintic nonlinearity subject to spatially
      heterogeneous forcing. Different types of forcing (sinusoidal or Gaussian) with
      different spatial scales are considered and the corresponding localized snaking
      structures are computed. The results indicate that spatial heterogeneity exerts a
      significant influence on the location of spatially localized structures in both
      parameter space and physical space, and on their stability properties. The
      results are expected to assist in the interpretation of experiments on localized
      structures where departures from spatial homogeneity are generally unavoidable. 

PMID- 24580294
TI  - Phase diagram for the Kuramoto model with van Hemmen interactions.
AB  - We consider a Kuramoto model of coupled oscillators that includes quenched random
      interactions of the type used by van Hemmen in his model of spin glasses. The
      phase diagram is obtained analytically for the case of zero noise and a
      Lorentzian distribution of the oscillators' natural frequencies. Depending on the
      size of the attractive and random coupling terms, the system displays four
      states: complete incoherence, partial synchronization, partial antiphase
      synchronization, and a mix of antiphase and ordinary synchronization. 

PMID- 24580295
TI  - Permutation entropy and statistical complexity quantifier of nonstationarity
      effect in the vertical velocity records.
AB  - How the nonstationarity in the atmosphere turbulent vertical velocity series
      affects its organization degree of multiscale structures is quantified by
      permutation entropy (PE) and complexity-entropy causality plane (CECP), and
      marked PE and CECP differences are detected between the nonstationary and
      stationary series. We find that the value of PE is lower in the nonstationary
      vertical velocity series than the stationary counterparts. Both types of series
      locate near the region of the higher complexity value in the CECP as chaotic
      systems, but the PE is smaller and the complexity degree is larger in the
      nonstationary series than the stationary with smaller time delays. Due to the
      close relationship between PE and the multiscale Shannon entropy, we show that
      the PE and CECP can be also taken as an indicator to quantify the different
      organization degrees of the multiscale structures existing between the stationary
      and nonstationary surface vertical velocity records. 

PMID- 24580296
TI  - Nonlinear response of a linear chain to weak driving.
AB  - We study the escape of a chain of coupled units over the barrier of a metastable
      potential. It is demonstrated that a very weak external driving field with a
      suitably chosen frequency suffices to accomplish speedy escape. The latter
      requires passage through a transition state, the formation of which is triggered
      by permanent feeding of energy from a phonon background into humps of localized
      energy and elastic interaction of the arising breather solutions. In fact,
      cooperativity between the units of the chain entailing coordinated energy
      transfer is shown to be crucial for enhancing the rate of escape in an extremely
      effective and low-energy cost way where the effects of entropic localization and
      breather coalescence conspire. 

PMID- 24580297
TI  - Extended nonlinear Schrodinger equation with higher-order odd and even terms and
      its rogue wave solutions.
AB  - We consider an extended nonlinear Schrodinger equation with higher-order odd
      (third order) and even (fourth order) terms with variable coefficients. The
      resulting equation has soliton solutions and approximate rogue wave solutions. We
      present these solutions up to second order. Moreover, specific constraints on the
      parameters of higher-order terms provide integrability of the resulting equation,
      providing a corresponding Lax pair. Particular cases of this equation are the
      Hirota and the Lakshmanan-Porsezian-Daniel equations. The resulting integrable
      equation admits exact rogue wave solutions. In particular cases, mentioned above,
      these solutions are reduced to the rogue wave solutions of the corresponding
      equations. 

PMID- 24580298
TI  - Analytical and experimental study of two delay-coupled excitable units.
AB  - We investigate the onset of time-periodic oscillations for a system of two
      identical delay-coupled excitable (nonoscillatory) units. We first analyze these
      solutions by using asymptotic methods. The oscillations are described as
      relaxation oscillations exhibiting successive slow and fast changes. The analysis
      highlights the determinant role of the delay during the fast transition layers.
      We then study experimentally a system of two coupled electronic circuits that is
      modeled mathematically by the same delay differential equations. We obtain
      quantitative agreements between analytical and experimental bifurcation diagrams.

PMID- 24580299
TI  - Identification of a separation wave number between weak and strong turbulence
      spectra for a vibrating plate.
AB  - A weakly nonlinear spectrum and a strongly nonlinear spectrum coexist in a
      statistically steady state of elastic wave turbulence. The analytical
      representation of the nonlinear frequency is obtained by evaluating the extended
      self-nonlinear interactions. The critical wave numbers at which the nonlinear
      frequencies are comparable with the linear frequencies agree with the separation
      wave numbers between the weak and strong turbulence spectra. We also confirm the
      validity of our analytical representation of the separation wave numbers through
      comparison with the results of direct numerical simulations by changing the
      material parameters of a vibrating plate. 

PMID- 24580300
TI  - Dynamics of the Kuramoto model in the presence of correlation between
      distributions of frequencies and coupling strengths.
AB  - As a paradigmatic model, the Kuramoto model has provided a platform for
      investigating synchronization among nonidentical oscillators. In this work, we
      consider the Kuramoto model consisting of conformists with positive coupling
      strength and contrarians with negative coupling strength. We introduce the
      correlation between the distributions of natural frequencies and the coupling
      strengths of oscillators. Three different types of correlations are considered.
      We find rich dynamics result from the correlation such as different types of
      traveling wave states and, most interestingly, another type of nonstationary
      state: an oscillating pi state. 

PMID- 24580301
TI  - Stochastic approach to diffusion inside the chaotic layer of a resonance.
AB  - We model chaotic diffusion in a symplectic four-dimensional (4D) map by using the
      result of a theorem that was developed for stochastically perturbed integrable
      Hamiltonian systems. We explicitly consider a map defined by a free rotator (FR)
      coupled to a standard map (SM). We focus on the diffusion process in the action I
      of the FR, obtaining a seminumerical method to compute the diffusion coefficient.
      We study two cases corresponding to a thick and a thin chaotic layer in the SM
      phase space and we discuss a related conjecture stated in the past. In the first
      case, the numerically computed probability density function for the action I is
      well interpolated by the solution of a Fokker-Planck (FP) equation, whereas it
      presents a nonconstant time shift with respect to the concomitant FP solution in
      the second case suggesting the presence of an anomalous diffusion time scale. The
      explicit calculation of a diffusion coefficient for a 4D symplectic map can be
      useful to understand the slow diffusion observed in celestial mechanics and
      accelerator physics. 

PMID- 24580302
TI  - Noise-induced synchronization of oscillatory convection and its optimization.
AB  - We investigate common-noise-induced phase synchronization between uncoupled
      identical Hele-Shaw cells exhibiting oscillatory convection. Using the phase
      description method for oscillatory convection, we demonstrate that the uncoupled
      systems of oscillatory Hele-Shaw convection can exhibit in-phase synchronization
      when driven by weak common noise. We derive the Lyapunov exponent determining the
      relaxation time for the synchronization, and develop a method for obtaining the
      optimal spatial pattern of the common noise to achieve synchronization. The
      theoretical results are confirmed by direct numerical simulations. 

PMID- 24580303
TI  - Spontaneous motion and deformation of a self-propelled droplet.
AB  - The time evolution equation of motion and shape are derived for a self-propelled
      droplet driven by a chemical reaction. The coupling between the chemical reaction
      and motion makes an inhomogeneous concentration distribution as well as a
      surrounding flow leading to the instability of a stationary state. The
      instability results in spontaneous motion by which the shape of the droplet
      deforms from a sphere. We found that the self-propelled droplet is elongated
      perpendicular to the direction of motion and is characterized as a pusher. 

PMID- 24580304
TI  - Formation of localized structures in bistable systems through nonlocal spatial
      coupling. I. General framework.
AB  - The present work studies the influence of nonlocal spatial coupling on the
      existence of localized structures in one-dimensional extended systems. We
      consider systems described by a real field with a nonlocal coupling that has a
      linear dependence on the field. Leveraging spatial dynamics we provide a general
      framework to understand the effect of the nonlocality on the shape of the fronts
      connecting two stable states. In particular we show that nonlocal terms can
      induce spatial oscillations in the front tails, allowing for the creation of
      localized structures, that emerge from pinning between two fronts. In parameter
      space the region where fronts are oscillatory is limited by three transitions:
      the modulational instability of the homogeneous state, the Belyakov-Devaney
      transition in which monotonic fronts acquire spatial oscillations with infinite
      wavelength, and a crossover in which monotonically decaying fronts develop
      spatial oscillations with a finite wavelength. We show how these transitions are
      organized by codimension 2 and 3 points and illustrate how by changing the
      parameters of the nonlocal coupling it is possible to bring the system into the
      region where localized structures can be formed. 

PMID- 24580305
TI  - Formation of localized structures in bistable systems through nonlocal spatial
      coupling. II. The nonlocal Ginzburg-Landau equation.
AB  - We study the influence of a linear nonlocal spatial coupling on the interaction
      of fronts connecting two equivalent stable states in the prototypical 1
      dimensional real Ginzburg-Landau equation. While for local coupling the fronts
      are always monotonic and therefore the dynamical behavior leads to coarsening and
      the annihilation of pairs of fronts, nonlocal terms can induce spatial
      oscillations in the front, allowing for the creation of localized structures,
      emerging from pinning between two fronts. We show this for three different
      nonlocal influence kernels. The first two, mod-exponential and Gaussian, are
      positive definite and decay exponentially or faster, while the third one, a
      Mexican-hat kernel, is not positive definite. 

PMID- 24580306
TI  - Tunable Fermi acceleration in a nondissipative driven magnetic billiard.
AB  - We study the effect of a constant magnetic field on the dynamics of a system that
      may present Fermi acceleration (FA). The model in consideration is the
      nondissipative annular billiard with breathing boundaries. There is a field
      threshold, from which the mechanism of FA can be deactivated. The presence of the
      magnetic field curves the particle trajectories and for some combinations of the
      parameters FA is totally, and nontrivially, suppressed without considering any
      kind of dissipation. 

PMID- 24580307
TI  - Chaotic dynamics in a two-dimensional optical lattice.
AB  - The classical nonlinear dynamics of a dilute gas of rubidium atoms in an optical
      lattice is studied for a range of polarizations of the laser beams forming the
      lattice. The dynamics ranges from integrable to chaotic, and mechanisms leading
      to the onset of chaos in the lattice are described. 

PMID- 24580308
TI  - Formation and collision of traveling bands in interacting deformable self
      propelled particles.
AB  - We study the collective dynamics of interacting deformable self-propelled
      particles whose migration velocity increases with increasing local density. In
      two-dimensional numerical simulations of this system, the local density
      dependence on migration velocity leads to traveling bands similar to those
      previously reported for Vicsek-type models. We show that a pair of straight bands
      moving in opposite directions survives a head-on collision. Although traveling
      bands also appear in systems of constant migration velocity subjected to random
      noise, they are found to be unstable in a head-on collision. 

PMID- 24580309
TI  - Dynamical monodromy.
AB  - Integrable Hamiltonian systems are said to display nontrivial monodromy if
      fundamental action-angle loops defined on phase-space tori change their
      topological structure when the system is carried around a circuit. In an earlier
      paper it was shown that this topological change can occur as a result of time
      evolution under certain rather abstract flows in phase space. In the present
      paper, we show that the same topological change can occur as a result of
      application of ordinary forces. We also show how this dynamical phenomenon could
      be observed experimentally in classical or in quantum systems. 

PMID- 24580310
TI  - Equation of state of an ideal gas with nonergodic behavior in two connected
      vessels.
AB  - We consider a two-dimensional collisionless ideal gas in the two vessels
      connected through a small hole. One of them is a well-behaved chaotic billiard,
      another one is known to be nonergodic. A significant part of the second vessel's
      phase space is occupied by an island of stability. In the works of Zaslavsky and
      coauthors, distribution of Poincare recurrence times in similar systems was
      considered. We study the gas pressure in the vessels; it is uniform in the first
      vessel and not uniform in second one. An equation of the gas state in the first
      vessel is obtained. Despite the very different phase-space structure, behavior of
      the second vessel is found to be very close to the behavior of a good ergodic
      billiard but of different volume. The equation of state differs from the ordinary
      equation of ideal gas state by an amendment to the vessel's volume. Correlation
      of this amendment with a share of the phase space under remaining intact islands
      of stability is shown. 

PMID- 24580311
TI  - Suppression of deterministic and stochastic extreme desynchronization events
      using anticipated synchronization.
AB  - We numerically show that extreme events induced by parameter mismatches or noise
      in coupled oscillatory systems can be anticipated and suppressed before they
      actually occur. We show this in a main system unidirectionally coupled to an
      auxiliary system subject to a negative delayed feedback. Each system consists of
      two electronic oscillators coupled in a master-slave configuration. Extreme
      events are observed in this coupled system as large and sporadic
      desynchronization events. Under certain conditions, the auxiliary system can
      predict the dynamics of the main system. We use this to efficiently suppress the
      extreme events by applying a direct corrective reset to the main system. 

PMID- 24580312
TI  - Chronotaxic systems with separable amplitude and phase dynamics.
AB  - Until recently, deterministic nonautonomous oscillatory systems with stable
      amplitudes and time-varying frequencies were not recognized as such and have
      often been mistreated as stochastic. These systems, named chronotaxic, were
      introduced in Phys. Rev. Lett. 111, 024101 (2013). In contrast to conventional
      limit cycle models of self-sustained oscillators, these systems posses a time
      dependent point attractor or steady state. This allows oscillations with time
      varying frequencies to resist perturbations, a phenomenon which is ubiquitous in
      living systems. In this work a detailed theory of chronotaxic systems is
      presented, specifically in the case of separable amplitude and phase dynamics.
      The theory is extended by the introduction of chronotaxic amplitude dynamics. The
      wide applicability of chronotaxic systems to a range of fields from biological
      and condensed matter systems to robotics and control theory is discussed. 

PMID- 24580313
TI  - Absence of exponential sensitivity to small perturbations in nonintegrable
      systems of spins 1/2.
AB  - We show that macroscopic nonintegrable lattices of spins 1/2, which are often
      considered to be chaotic, do not exhibit the basic property of classical chaotic
      systems, namely, exponential sensitivity to small perturbations. We compare
      chaotic lattices of classical spins and nonintegrable lattices of spins 1/2 in
      terms of their magnetization responses to an imperfect reversal of spin dynamics
      known as Loschmidt echo. In the classical case, magnetization is exponentially
      sensitive to small perturbations with a characteristic exponent equal to twice
      the value of the largest Lyapunov exponent of the system. In the case of spins
      1/2, magnetization is only power-law sensitive to small perturbations. 

PMID- 24580314
TI  - Transient growth of Ekman-Couette flow.
AB  - Coriolis force effects on shear flows are important in geophysical and
      astrophysical contexts. We report a study on the linear stability and the
      transient energy growth of the plane Couette flow with system rotation
      perpendicular to the shear direction. External rotation causes linear
      instability. At small rotation rates, the onset of linear instability scales
      inversely with the rotation rate and the optimal transient growth in the linearly
      stable region is slightly enhanced ~Re2. The corresponding optimal initial
      perturbations are characterized by roll structures inclined in the streamwise
      direction and are twisted under external rotation. At large rotation rates, the
      transient growth is significantly inhibited and hence linear stability analysis
      is a reliable indicator for instability. 

PMID- 24580315
TI  - Three-dimensional inverse energy transfer induced by vortex reconnections.
AB  - In low-temperature superfluid helium, viscosity is zero and vorticity takes the
      form of discrete vortex filaments of fixed circulation and atomic thickness. We
      present numerical evidence of three-dimensional inverse energy transfer from
      small length scales to large length scales in superfluid turbulence generated by
      a flow of vortex rings. We argue that the effect arises from the anisotropy of
      the flow, which favors vortex reconnections of vortex loops of the same polarity,
      and that it has been indirectly observed in the laboratory. The effect opens
      questions about analogies with related processes in ordinary turbulence. 

PMID- 24580316
TI  - Effect of the fluid injection configuration on droplet size in a microfluidic T
      junction.
AB  - The effect of confinement on the droplet formation in T junctions was studied for
      three configurations of fluid injection. The sizes of the main droplets and the
      satellite droplets were measured in the squeezing and dripping regimes. The
      evolution of droplet sizes with capillary number in the continuous phase is
      similar to that in flow-focusing junctions, i.e., the size of the main droplets
      decreases with an increase of this capillary number, while the size of the
      satellite droplets increases with an increase of this capillary number. While in
      the range of flow rates investigated the injection configuration does not exhibit
      a significant effect on the main droplet sizes, it does have an effect on the
      size of the satellite droplets. The latter ones are smaller when the neck rupture
      of the droplet occurs on an angle of the microsystem. 

PMID- 24580317
TI  - Viscoelasticity and shear thinning of nanoconfined water.
AB  - Understanding flow properties and phase behavior of water confined to nanometer
      sized pores and slits is central to a wide range of problems in science, such as
      percolation in geology, lubrication of future nano-machines, self-assembly and
      interactions of biomolecules, and transport through porous media in filtration
      processes. Experiments with different techniques in the past have reported that
      viscosity of nanoconfined water increases, decreases, or remains close to bulk
      water. Here we show that water confined to less than 20-nm-thick films exhibits
      both viscoelasticity and shear thinning. Typically viscoelasticity and shear
      thinning appear due to shearing of complex non-Newtonian mixtures possessing a
      slowly relaxing microstructure. The shear response of nanoconfined water in a
      range of shear frequencies (5 to 25 KHz) reveals that relaxation time diverges
      with reducing film thickness. It suggests that slow relaxation under confinement
      possibly arises due to existence of a critical point with respect to slit width.
      This criticality is similar to the capillary condensation in porous media. 

PMID- 24580318
TI  - Numerical study of turbulent flow over complex aeolian dune fields: the White
      Sands National Monument.
AB  - The structure and dynamics of fully developed turbulent flows responding to
      aeolian dune fields are studied using large-eddy simulation with an immersed
      boundary method. An aspect of particular importance in these flows is the
      downwind migration of coherent motions associated with Kelvin-Helmholtz
      instabilities that originate at the dune crests. These instabilities are
      responsible for enhanced downward transport of high-momentum fluid via the so
      called turbulent sweep mechanism. However, the presence of such structures and
      their role in determining the bulk characteristics of fully developed dune field
      sublayer aerodynamics have received relatively limited attention. Moreover, many
      existing studies address mostly symmetric or mildly asymmetric dune forms. The
      White Sands National Monument is a field of aeolian gypsum sand dunes located in
      the Tularosa Basin in southern New Mexico. Aeolian processes at the site result
      in a complex, anisotropic dune field. In the dune field sublayer, the flow
      statistics resemble a mixing layer: At approximately the dune crest height,
      vertical profiles of streamwise velocity exhibit an inflection and turbulent
      Reynolds stresses are maximum; below this, the streamwise and vertical velocity
      fluctuations are positively and negatively skewed, respectively. We evaluate the
      spatial structure of Kelvin-Helmholtz instabilities present in the dune field
      sublayer (shear length L(s) and vortex spacing Lambda(x)) and show that
      Lambda(x)=m(dune)L(s), where m(dune)~7.2 in the different sections considered
      (for turbulent mixing layers, 7<m<10 [M. M. Rogers and R. D. Moser, Phys. Fluids
      A 6, 903 (1994)]).

PMID- 24580319
TI  - Simulation of finite-size fibers in turbulent channel flows.
AB  - The dynamical behavior of almost neutrally buoyant finite-size rigid fibers or
      rods in turbulent channel flow is studied by direct numerical simulations. The
      time evolution of the fiber orientation and translational and rotational motions
      in a statistically steady channel flow is obtained for three different fiber
      lengths. The turbulent flow is modeled by an entropy lattice Boltzmann method,
      and the interaction between fibers and carrier fluid is modeled through an
      external boundary force method. Direct contact and lubrication force models for
      fiber-fiber interactions and fiber-wall interaction are taken into account to
      allow for a full four-way interaction. The density ratio is chosen to mimic
      cellulose fibers in water. It is shown that the finite size leads to fiber
      turbulence interactions that are significantly different from earlier reported
      results for pointlike particles (e.g., elongated ellipsoids smaller than the
      Kolmogorov scale). An effect that becomes increasingly accentuated with fiber
      length is an accumulation in high-speed regions near the wall, resulting in a
      mean fiber velocity that is higher than the mean fluid velocity. The simulation
      results indicate that the finite-size fibers tend to stay in the high-speed
      streaks due to collisions with the wall. In the central region of the channel,
      long fibers tend to align in the spanwise direction. Closer to the wall the long
      fibers instead tend to toward to a rotation in the shear plane, while very close
      to the wall they become predominantly aligned in the streamwise direction. 

PMID- 24580320
TI  - Three-dimensional Marangoni cell in self-induced evaporating cooling unveiled by
      digital holographic microscopy.
AB  - A digital holographic microscope has been used to trace the trajectory of a
      tracer particle inside the liquid phase of an evaporating meniscus formed at the
      mouth of a 1-mm2 borosilicate tube filled with ethanol. The Marangoni flow cells
      are generated by the self-induced differential evaporating cooling along the
      meniscus interface that creates gradients of surface tension which drive the
      convection. The competition between surface tension and gravity forces along the
      curved meniscus interface disrupts the symmetry due to surface tension alone.
      This distorts the shape of the toroidal Marangoni vortex. Thermocapillary
      instabilities of the evaporating meniscus are reported by analyzing the
      trajectories of the tracer particle. It is found that the trajectory of the
      tracer particle makes different three-dimensional loops and every four loops it
      returns to the first loop. By analyzing several loops it was found that the
      characteristic frequency of the periodic oscillatory motion is around 0.125 Hz. 

PMID- 24580321
TI  - Numerical analysis of a red blood cell flowing through a thin micropore.
AB  - Red blood cell (RBC) deformability plays a key role in microcirculation,
      especially in vessels that have diameters even smaller than the nominal cell
      size. In this study, we numerically investigate the dynamics of an RBC in a thin
      micropore. The RBC is modeled as a capsule with a thin hyperelastic membrane. In
      a numerical simulation, we employ a boundary element method for fluid mechanics
      and a finite element method for membrane mechanics. The resulting RBC deformation
      towards the flow direction is suppressed considerably by increased cytoplasm
      viscosity, whereas the gap between the cell membrane and solid wall becomes
      smaller with higher cytoplasm viscosity. We also measure the transit time of the
      RBC and find that nondimensional transit time increases nonlinearly with respect
      to the viscosity ratio, whereas it is invariant to the capillary number. In
      conclusion, cytoplasmic viscosity plays a key role in the dynamics of an RBC in a
      thin pore. The results of this study will be useful for designing a microfluidic
      device to measure cytoplasmic viscosity. 

PMID- 24580322
TI  - Free turbulent shear layer in a point vortex gas as a problem in nonequilibrium
      statistical mechanics.
AB  - This paper attempts to unravel any relations that may exist between turbulent
      shear flows and statistical mechanics through a detailed numerical investigation
      in the simplest case where both can be well defined. The flow considered for the
      purpose is the two-dimensional (2D) temporal free shear layer with a velocity
      difference DeltaU across it, statistically homogeneous in the streamwise
      direction (x) and evolving from a plane vortex sheet in the direction normal to
      it (y) in a periodic-in-x domain L*+/-infinity. Extensive computer simulations of
      the flow are carried out through appropriate initial-value problems for a "vortex
      gas" comprising N point vortices of the same strength (gamma=LDeltaU/N) and sign.
      Such a vortex gas is known to provide weak solutions of the Euler equation. More
      than ten different initial-condition classes are investigated using simulations
      involving up to 32000 vortices, with ensemble averages evaluated over up to 103
      realizations and integration over 104L/DeltaU. The temporal evolution of such a
      system is found to exhibit three distinct regimes. In Regime I the evolution is
      strongly influenced by the initial condition, sometimes lasting a significant
      fraction of L/DeltaU. Regime III is a long-time domain-dependent evolution
      towards a statistically stationary state, via "violent" and "slow" relaxations [
      P.-H. Chavanis Physica A 391 3657 (2012)], over flow time scales of order 102 and
      104L/DeltaU, respectively (for N=400). The final state involves a single
      structure that stochastically samples the domain, possibly constituting a
      "relative equilibrium." The vortex distribution within the structure follows a
      nonisotropic truncated form of the Lundgren-Pointin (L-P) equilibrium
      distribution (with negatively high temperatures; L-P parameter lambda close to 
      1). The central finding is that, in the intermediate Regime II, the spreading
      rate of the layer is universal over the wide range of cases considered here. The
      value (in terms of momentum thickness) is 0.0166+/-0.0002 times DeltaU. Regime
      II, extensively studied in the turbulent shear flow literature as a self-similar
      "equilibrium" state, is, however, a part of the rapid nonequilibrium evolution of
      the vortex-gas system, which we term "explosive" as it lasts less than one
      L/DeltaU. Regime II also exhibits significant values of N-independent two-vortex
      correlations, indicating that current kinetic theories that neglect correlations
      or consider them as O(1/N) cannot describe this regime. The evolution of the
      layer thickness in present simulations in Regimes I and II agree with the
      experimental observations of spatially evolving (3D Navier-Stokes) shear layers.
      Further, the vorticity-stream-function relations in Regime III are close to those
      computed in 2D Navier-Stokes temporal shear layers [ J. Sommeria, C. Staquet and
      R. Robert J. Fluid Mech. 233 661 (1991)]. These findings suggest the dominance of
      what may be called the Kelvin-Biot-Savart mechanism in determining the growth of
      the free shear layer through large-scale momentum and vorticity dispersal. 

PMID- 24580323
TI  - Restricted partition functions and inverse energy cascades in parity symmetry
      breaking flows.
AB  - When the symmetries of homogenous isotropic turbulent flows are broken, different
      sets of modes with different physical roles emerge. In particular, choosing a
      forcing which puts more weight on one or the other of these sets may result in
      different statistics for the energy transfers. We use the general method of
      computing a partition function restricted to a portion of phase space to study
      analytically these different statistics. We illustrate this method in the case of
      parity symmetry breaking, measured by helicity. It is shown that when helicity is
      sign-definite at all scales, an inverse cascade is expected for the energy. When
      sign-definiteness is lost, even for a small set of modes, this cascade disappears
      and there is a sharp phase transition to the standard helical equipartition
      spectra. 

PMID- 24580324
TI  - Unorthodox bubbles when boiling in cold water.
AB  - High-speed movies are taken when bubbles grow at gold surfaces heated spotwise
      with a near-infrared laser beam heating water below the boiling point (60-70 
      degrees C) with heating powers spanning the range from very low to so high that
      water fails to rewet the surface after bubbles detach. Roughly half the bubbles
      are conventional: They grow symmetrically through evaporation until buoyancy
      lifts them away. Others have unorthodox shapes and appear to contribute
      disproportionately to heat transfer efficiency: mushroom cloud shapes, violently
      explosive bubbles, and cavitation events, probably stimulated by a combination of
      superheating, convection, turbulence, and surface dewetting during the initial
      bubble growth. Moreover, bubbles often follow one another in complex sequences,
      often beginning with an unorthodox bubble that stirs the water, followed by
      several conventional bubbles. This large dataset is analyzed and discussed with
      emphasis on how explosive phenomena such as cavitation induce discrepancies from
      classical expectations about boiling. 

PMID- 24580325
TI  - Effect of soft-iron impellers on the von Karman-sodium dynamo.
AB  - The explanation for the observed axisymmetric magnetic field in the von Karman
      sodium (VKS) dynamo experiment is still an unresolved question. In this paper,
      the integral equation approach is extended to investigate the VKS dynamo action
      by taking into account the discontinuity of the magnetic permeability and
      electrical conductivity in the conducting region. When the relative magnetic
      permeability of the soft-iron impellers is set to 65, a steady toroidal field
      that is apparently axisymmetric is excited at the critical magnetic Reynolds
      number, Rmc~27.23, which is close to the experimental result, Rmc~30. Our results
      show that the critical magnetic Reynolds number declines as the relative magnetic
      permeability of the impellers increases. Furthermore, when the relative magnetic
      permeability is not greater than 37, an equatorial magnetic field with an
      azimuthal wave number m=1 is the dominant mode, otherwise a steady toroidal field
      with an azimuthal wave number m=0 predominates the magnetic field generated by
      the VKS dynamo action. 

PMID- 24580326
TI  - Rapidly rotating cylinder flow with an oscillating sidewall.
AB  - We present numerical simulations of a flow in a rapidly rotating cylinder
      subjected to a time-periodic forcing via axial oscillations of the sidewall. When
      the axial oscillation frequency is less than twice the rotation frequency,
      inertial waves in the form of shear layers are present. For very fast rotations,
      these waves approach the form of the characteristics predicted from the
      linearized inviscid problem first studied by Lord Kelvin. The driving mechanism
      for the inertial waves is the oscillating Stokes layer on the sidewall and the
      corner discontinuities where the sidewall meets the top and bottom end walls. A
      detailed numerical and theoretical analysis of the internal shear layers is
      presented. The system is physically realizable, and attractive because of the
      robustness of the Stokes layer that drives the inertial waves but beyond that
      does not interfere with them. We show that the system loses stability to
      complicated three-dimensional flow when the sidewall oscillation displacement
      amplitude is very large (of the order of the cylinder radius), but this is far
      removed from the displacement amplitudes of interest, and there is a large range
      of governing parameters which are physically realizable in experiments in which
      the inertial waves are robust. This is in contrast to many other physical
      realizations of inertial waves where the driving mechanisms tend to lead to
      instabilities and complicate the study of the waves. We have computed the
      response diagram of the system for a large range of forcing frequencies and
      compared the results with inviscid eigenmodes and ray tracing techniques. 

PMID- 24580327
TI  - Influence of sedimentation on the threshold for Soret-driven convection in
      colloidal suspensions.
AB  - The onset of Soret-driven convection in a horizontal layer of a colloidal
      suspension is investigated by considering a particulate medium model. We consider
      a dilute suspension of spherical solid particles being subjected to convection in
      a Rayleigh-Benard geometry setup. The mathematical model takes into account the
      effects of thermophoresis, particle sedimentation, and Brownian diffusion. The
      equations governing the convective motion consist of the momentum equation which
      includes an extra body force term to account for the thermophoretic force effect,
      the conservation of particles equation whose mass-flux term couples the Soret and
      particle diffusion effects and whose advective term includes the sedimentation
      force, and the heat and mass balance equations. The horizontal boundaries are
      assumed rigid, perfectly thermally conducting, and impervious to mass flow.
      Furthermore, the model makes use of the effective viscosity of the suspension
      whose dependence on the particle concentration is through Einstein's formula.
      Moreover, we take into account the decrease of both the coefficient of Brownian
      diffusion and the mixture thermal diffusion with particle concentration due to
      the particles hindrance effect. The nondimensionalization leads to the emergence
      of an experimental parameter, beta, which depicts the competition between the
      effects of thermophoresis, sedimentation, and particle diffusion. The parameter
      beta is a function of the particles radius, the shape of which is an inverted
      parabola having two zeros. A combination of asymptotic and numerical computations
      is used to determine the threshold for the onset of the mass dominated
      convection, which corresponds to 0<beta?1. Our findings shed light on the role of
      particle sedimentation and particle size, as well as the influence of other
      processing variables on the fluid instability. 

PMID- 24580328
TI  - Scaling laws for drop impingement on porous films and papers.
AB  - This study investigates drop impingement on highly wetting porous films and
      papers. Experiments reveal previously unexplored impingement modes on porous
      surfaces designated as necking, spreading, and jetting. Dimensional analysis
      yields a nondimensional parameter, denoted the Washburn-Reynolds number, relating
      droplet kinetic energy and surface energy. The impingement modes correlate with
      Washburn-Reynolds number variations spanning four orders of magnitude and a
      corresponding energy conservation analysis for droplet spreading shows good
      agreement with the experimental results. The simple scaling laws presented will
      inform the investigation of dynamic interactions between porous surfaces and
      liquid drops. 

PMID- 24580329
TI  - Controlling and minimizing fingering instabilities in non-Newtonian fluids.
AB  - The development of the viscous fingering instability in Hele-Shaw cells has great
      practical and scientific importance. Recently, researchers have proposed
      different strategies to control the number of interfacial fingering structures,
      or to minimize as much as possible the amplitude of interfacial disturbances.
      Most existing studies address the situation in which an inviscid fluid displaces
      a viscous Newtonian fluid. In this work, we report on controlling and minimizing
      protocols considering the situation in which the displaced fluid is a non
      Newtonian, power-law fluid. The necessary changes on the controlling schemes due
      to the shear-thinning and shear thickening nature of the displaced fluid are
      calculated analytically and discussed. 

PMID- 24580330
TI  - Fluctuating hydrodynamics of multispecies nonreactive mixtures.
AB  - In this paper we discuss the formulation of the fluctuating Navier-Stokes
      equations for multispecies, nonreactive fluids. In particular, we establish a
      form suitable for numerical solution of the resulting stochastic partial
      differential equations. An accurate and efficient numerical scheme, based on our
      previous methods for single species and binary mixtures, is presented and tested
      at equilibrium as well as for a variety of nonequilibrium problems. These include
      the study of giant nonequilibrium concentration fluctuations in a ternary mixture
      in the presence of a diffusion barrier, the triggering of a Rayleigh-Taylor
      instability by diffusion in a four-species mixture, as well as reverse diffusion
      in a ternary mixture. Good agreement with theory and experiment demonstrates that
      the formulation is robust and can serve as a useful tool in the study of thermal
      fluctuations for multispecies fluids. 

PMID- 24580331
TI  - Relationship between pore size and velocity probability distributions in
      stochastically generated porous media.
AB  - We perform a set of detailed numerical simulations of single-phase, fully
      saturated flow in stochastically generated, three-dimensional pore structures
      with diverse porosities (phi) and degrees of connectivity, and analyze the
      probability density functions (PDFs) of the pore sizes, S, and vertical velocity
      components, w, which are aligned with the mean flow direction. Both of the PDFs
      are markedly skewed with pronounced positive tails. This feature of the velocity
      PDF is dictated by the pore structure and determines the shortest travel times,
      one of the key transport attributes that underpins the success or the failure of
      environmental remediation techniques. Using a maximum likelihood approach, we
      determine that the PDFs of S and w decay according to an exponential and a
      stretched exponential model, respectively. A strong correlation between the key
      parameters governing the decay of the upper tails of the two PDFs is found, which
      provides a quantitative result for this analogy that so far has been stated only
      qualitatively. The parameter governing the concavity of the tail of the velocity
      PDF varies linearly with porosity over the entire range of tested values
      (0.2<=phi<=0.6). The parameters controlling the spread of the upper tails of the
      PDFs of S and w appear to be linked by a power-law relationship. 

PMID- 24580332
TI  - Confined rotating convection with large Prandtl number: centrifugal effects on
      wall modes.
AB  - Thermal convection in a rotating cylinder with a radius-to-height aspect ratio of
      Gamma=4 for fluids with large Prandtl number is studied numerically. Centrifugal
      buoyancy effects are investigated in a regime where the Coriolis force is
      relatively large and the onset of thermal convection is in the so-called wall
      modes regime, where pairs of hot and cold thermal plumes ascend and descend in
      the cylinder sidewall boundary layer, forming an essentially one-dimensional
      pattern characterized by the number of hot and cold plume pairs. In our numerical
      study, we use the physical parameters corresponding to aqueous mixtures of
      glycerine with mass concentration in the range of 60%-90% glycerine and a
      Rayleigh number range that extends from the threshold for wall modes up to values
      where the bulk fluid region is also convecting. The study shows that for the
      range of Rayleigh numbers considered, the local variations in viscosity due to
      temperature variation in the flow are negligible. However, the mean viscosity,
      which varies faster than exponentially with variations in the percentage of
      glycerine, leads to a faster than exponential increase in the Froude number for a
      fixed Coriolis force, and hence an enhancement of the centrifugal buoyancy
      effects with significant dynamical consequences, which are detailed. 

PMID- 24580333
TI  - Nonlinear dynamics and anisotropic structure of rotating sheared turbulence.
AB  - Homogeneous turbulence in rotating shear flows is studied by means of
      pseudospectral direct numerical simulation and analytical spectral linear theory
      (SLT). The ratio of the Coriolis parameter to shear rate is varied over a wide
      range by changing the rotation strength, while a constant moderate shear rate is
      used to enable significant contributions to the nonlinear interscale energy
      transfer and to the nonlinear intercomponental redistribution terms. In the
      destabilized and neutral cases, in the sense of kinetic energy evolution,
      nonlinearity cannot saturate the growth of the largest scales. It permits the
      smallest scale to stabilize by a scale-by-scale quasibalance between the
      nonlinear energy transfer and the dissipation spectrum. In the stabilized cases,
      the role of rotation is mainly nonlinear, and interacting inertial waves can
      affect almost all scales as in purely rotating flows. In order to isolate the
      nonlinear effect of rotation, the two-dimensional manifold with vanishing
      spanwise wave number is revisited and both two-component spectra and single-point
      two-dimensional energy components exhibit an important effect of rotation,
      whereas the SLT as well as the purely two-dimensional nonlinear analysis are
      unaffected by rotation as stated by the Proudman theorem. The other two
      dimensional manifold with vanishing streamwise wave number is analyzed with
      similar tools because it is essential for any shear flow. Finally, the spectral
      approach is used to disentangle, in an analytical way, the linear and nonlinear
      terms in the dynamical equations. 

PMID- 24580334
TI  - Generalized second-order slip boundary condition for nonequilibrium gas flows.
AB  - It is a challenging task to model nonequilibrium gas flows within a continuum
      fluid framework. Recently some extended hydrodynamic models in the Navier-Stokes
      formulation have been developed for such flows. A key problem in the application
      of such models is that suitable boundary conditions must be specified. In the
      present work, a generalized second-order slip boundary condition is developed in
      which an effective mean-free path considering the wall effect is used. By
      combining this slip scheme with certain extended Navier-Stokes constitutive
      relation models, we obtained a method for nonequilibrium gas flows with solid
      boundaries. The method is applied to several rarefied gas flows involving planar
      or curved walls, including the Kramers' problem, the planar Poiseuille flow, the
      cylindrical Couette flow, and the low speed flow over a sphere. The results show
      that the proposed method is able to give satisfied predictions, indicating the
      good potential of the method for nonequilibrium flows. 

PMID- 24580335
TI  - Faraday instability in a near-critical fluid under weightlessness.
AB  - Experiments on near-critical hydrogen have been conducted under magnetic
      compensation of gravity to investigate the Faraday instability that arises at the
      liquid-vapor interface under zero-gravity conditions. We investigated such
      instability in the absence of stabilizing gravity. Under such conditions,
      vibration orients the interface and can destabilize it. The experiments confirm
      the existence of Faraday waves and demonstrate a transition from a square to a
      line pattern close to the critical point. They also show a transition very close
      to the critical point from Faraday to periodic layering of the vapor-liquid
      interface perpendicular to vibration. It was seen that the Faraday wave
      instability is favored when the liquid-vapor density difference is large enough
      (fluid far from the critical point), whereas periodic layering predominates for
      small difference in the liquid and vapor densities (close to the critical point).
      It was observed for the Faraday wave instability that the wavelength of the
      instability decreases as one approaches the critical point. The experimental
      results demonstrate good agreement to the dispersion relation for zero gravity
      except for temperatures very close to the critical point where a transition from
      a square pattern to a line pattern is detected, similarly to what is observed
      under 1g conditions. 

PMID- 24580336
TI  - Droplet-air collision dynamics: evolution of the film thickness.
AB  - This study is devoted to the experimental and theoretical investigation of
      aerodynamic drop breakup phenomena. We show that the phenomena of drop impact
      onto a rigid wall, drop binary collisions, and aerodynamic drop deformation are
      similar if the correct scaling is applied. Then we use observations of the
      deforming drop to estimate the evolution of the film thickness of the bag, the
      value that determines the size of the fine child drops produced by bag breakup.
      This prediction of film thickness, based on film kinematics, is validated for the
      initial stage by direct drop thickness measurements and at the latest stage by
      the data obtained from the velocity of hole expansion in the film. It is shown
      that the film thickness correlates well with the dimensionless position of the
      bag apex. 

PMID- 24580337
TI  - Effects of three-dimensional geometric field focusing on concentration
      polarization in a heterogeneous permselective system.
AB  - The current study extends previous two-dimensional (2D) analysis of concentration
      polarization to account for three-dimensional effects in realistic heterogeneous
      ion-permselective systems, e.g., microchamber-nanoslot devices. An analytical
      solution of the electrodiffusive problem, decoupled from electroconvection along
      with the local electroneutrality approximation, was obtained using the separation
      of variables technique. It is able to account for the previously neglected
      effects of microchamber and nanoslot heights on concentration polarization in
      terms of concentration profiles, limiting current, and current-voltage curves.
      The resultant heterogeneity in the third dimension adds to that already existing
      in the 2D in plane problem to further increase geometric field-focusing effects.
      As a result the currents no longer scale linearly with the nanoslot area, but
      rather depend on its shape and relative size compared to that of the
      nonconducting region (i.e., level of heterogeneity). This is turn leads to
      pronounced current density intensification with increased system heterogeneity
      found to be in qualitative agreement with previously reported experiments in
      which both microchamber and nanoslot geometries were varied. 

PMID- 24580338
TI  - Thermodynamic theory of the shock wave structure in a rarefied polyatomic gas:
      beyond the Bethe-Teller theory.
AB  - The structure of a shock wave in a rarefied polyatomic gas is studied on the
      basis of the theory of extended thermodynamics. Three types of the shock wave
      structure observed in experiments, that is, the nearly symmetric shock wave
      structure (type A, small Mach number), the asymmetric structure (type B, moderate
      Mach number), and the structure composed of thin and thick layers (type C, large
      Mach number), are explained by the theory in a unified way. The theoretical
      prediction of the profile of the mass density agrees well with the experimental
      data. The well-known Bethe-Teller theory of the shock wave structure in a
      polyatomic gas is reexamined in the light of the present theory. 

PMID- 24580339
TI  - Direct velocity measurement of a turbulent shear flow in a planar Couette cell.
AB  - In a plane Couette cell a thin fluid layer consisting of water is sheared between
      the sides of a transparent band at Reynolds numbers ranging from 300 to 1400. The
      length of the cell's flow channel is large compared to the film separation. To
      extract the flow velocity in the experiments, a correlation image velocimetry
      method is used on pictures recorded with a high-speed camera. The flow is
      recorded at a resolution that allows us to analyze flow patterns similar in size
      to the film separation. The fluid flow is then studied by calculating flow
      velocity autocorrelation functions. The turbulent patterns that arise on this
      scale above a critical Reynolds number of Re=360 display characteristic patterns
      that are proven by use of the calculated velocity autocorrelation functions. The
      patterns are metastable and reappear at different positions and times throughout
      the experiments. Typically these patterns are turbulent rolls which are elongated
      in the stream direction, which is the direction in which the band is moving.
      Although the flow states are metastable they possess similarities to the steady
      Taylor vortices known to appear in circular Taylor Couette cells. 

PMID- 24580340
TI  - Transverse current fluctuations in the Yukawa one-component plasma.
AB  - Using numerical simulations, we investigate the wave number and frequency
      dependent transverse current correlation function CT(k,omega) of a single
      component fluid with Yukawa interaction potential, also known as the Yukawa one
      component plasma. The transverse current correlation function is an important
      quantity because it contains the microscopic details of the viscoelastic behavior
      of the fluid. We show that, in the region of densities and temperatures in which
      shear waves do not propagate, the dynamics of the system are in striking
      agreement with a simple model of generalized hydrodynamics. As either the density
      is increased or the temperature decreased, the transverse current correlation
      function shows additional structure that the simple models fail to capture. 

PMID- 24580341
TI  - Target charging in short-pulse-laser-plasma experiments.
AB  - Interaction of high-intensity laser pulses with solid targets results in
      generation of large quantities of energetic electrons that are the origin of
      various effects such as intense x-ray emission, ion acceleration, and so on. Some
      of these electrons are escaping the target, leaving behind a significant positive
      electric charge and creating a strong electromagnetic pulse long after the end of
      the laser pulse. We propose here a detailed model of the target electric
      polarization induced by a short and intense laser pulse and an escaping electron
      bunch. A specially designed experiment provides direct measurements of the target
      polarization and the discharge current in the function of the laser energy, pulse
      duration, and target size. Large-scale numerical simulations describe the
      energetic electron generation and their emission from the target. The model,
      experiment, and numerical simulations demonstrate that the hot-electron ejection
      may continue long after the laser pulse ends, enhancing significantly the
      polarization charge. 

PMID- 24580342
TI  - Effect of strong coupling on the dust acoustic instability.
AB  - In a plasma containing charged dust grains, the dust acoustic instability (DAI)
      can be driven by ions streaming through the dust with speed less than the ion
      thermal speed. When the dust is strongly coupled in the liquid phase, the
      dispersion relation of the dust acoustic modes changes in a way that leads to an
      enhancement of the growth rate of the DAI. In this paper, we show how strong
      coupling enhances the DAI growth rate and consider application to microgravity
      experiments where subthermal ion flows are in general possible. 

PMID- 24580343
TI  - Effect of strong wakes on waves in two-dimensional plasma crystals.
AB  - We study the effects of the particle-wake interactions on the dispersion and
      polarization of dust lattice wave modes in two-dimensional plasma crystals. Most
      notably, the wake-induced coupling between the modes causes the branches to
      "attract" each other, and their polarizations become elliptical. Upon the mode
      hybridization the major axes of the ellipses (remaining mutually orthogonal)
      rotate by 45 degrees . To demonstrate the importance of the obtained results for
      experiments, we plot representative particle trajectories and spectral densities
      of the longitudinal and transverse waves. These characteristics reveal distinct
      fingerprints of the mixed polarization. Furthermore, we show that at strong
      coupling the hybrid mode is significantly shifted towards smaller wave numbers,
      away from the border of the first Brillouin zone (where the hybrid mode is
      localized for a weak coupling).

PMID- 24580344
TI  - Dynamics of two-dimensional one-component and binary Yukawa systems in a magnetic
      field.
AB  - We consider two-dimensional Yukawa systems in a perpendicular magnetic field.
      Computer simulations of both one-component and binary systems are used to explore
      the equilibrium particle dynamics in the fluid state. The mobility is found to
      scale with the inverse of the magnetic field strength (Bohm diffusion), for
      strong fields (omegac/omegap?1). For bidisperse mixtures, the magnetic field
      dependence of the long-time mobility depends on the particle species, providing
      an external control of their mobility ratio. At large magnetic fields, the highly
      charged particles are almost immobilized by the magnetic field and form a porous
      matrix of obstacles for the mobile low-charge particles. 

PMID- 24580345
TI  - Effects of front-surface target structures on properties of relativistic laser
      plasma electrons.
AB  - We report the results of a study of the role of prescribed geometrical structures
      on the front of a target in determining the energy and spatial distribution of
      relativistic laser-plasma electrons. Our three-dimensional particle-in-cell
      simulation studies apply to short-pulse, high-intensity laser pulses, and
      indicate that a judicious choice of target front-surface geometry provides the
      realistic possibility of greatly enhancing the yield of high-energy electrons
      while simultaneously confining the emission to narrow (<5 degrees ) angular
      cones.

PMID- 24580346
TI  - Laser-driven three-stage heavy-ion acceleration from relativistic laser-plasma
      interaction.
AB  - A three-stage heavy ion acceleration scheme for generation of high-energy
      quasimonoenergetic heavy ion beams is investigated using two-dimensional particle
      in-cell simulation and analytical modeling. The scheme is based on the
      interaction of an intense linearly polarized laser pulse with a compound two
      layer target (a front heavy ion layer + a second light ion layer). We identify
      that, under appropriate conditions, the heavy ions preaccelerated by a two-stage
      acceleration process in the front layer can be injected into the light ion shock
      wave in the second layer for a further third-stage acceleration. These injected
      heavy ions are not influenced by the screening effect from the light ions, and an
      isolated high-energy heavy ion beam with relatively low-energy spread is thus
      formed. Two-dimensional particle-in-cell simulations show that ~100MeV/u
      quasimonoenergetic Fe24+ beams can be obtained by linearly polarized laser pulses
      at intensities of 1.1*1021W/cm2. 

PMID- 24580347
TI  - First principles nonequilibrium plasma mixing.
AB  - We have performed nonequilibrium classical and quantum-mechanical molecular
      dynamics simulations that follow the interpenetration of deuterium-tritium (DT)
      and carbon (C) components through an interface initially in hydrostatic and
      thermal equilibrium. We concentrate on the warm, dense matter regime with initial
      densities of 2.5-5.5 g/cm3 and temperatures from 10 to 100 eV. The classical
      treatment employs a Yukawa pair-potential with the parameters adjusted to the
      plasma conditions, and the quantum treatment rests on an orbital-free density
      functional theory at the Thomas-Fermi-Dirac level. For times greater than about a
      picosecond, the component concentrations evolve in accordance with Fick's law for
      a classically diffusing fluid with the motion, though, described by the mutual
      diffusion coefficient of the mixed system rather than the self-diffusion of the
      individual components. For shorter times, microscopic processes control the
      clearly non-Fickian dynamics and require a detailed representation of the
      electron probability density in space and time. 

PMID- 24580348
TI  - Nonequilibrium finite dust clusters: connecting normal modes and wakefields.
AB  - The dynamic properties of finite three-dimensional dust clusters in a dusty
      plasma under the influence of an ion focus are studied by normal modes. The mode
      analysis has been extended to account for the ion focus using the point-charge
      model for the horizontal interaction of the dust particles. From that, an
      analytical model for a few-particle system is derived accounting for three
      distinct dynamical regimes at different focus strengths, namely, absolutely
      unstable and fully stable configurations as well as an unstable oscillatory
      regime. The techniques of normal mode analysis (NMA) and instantaneous normal
      modes (INM) extended by the ion focus have been applied to dust systems in the
      experiment and compared to the model. From this, the ion focus strength has been
      derived. The specific sensitivity of NMA and INM allows one to identify
      equilibrium configurations in this nonequilibrium environment for these finite
      clusters. 

PMID- 24580349
TI  - Head-on collision of dust-acoustic solitons in a strongly coupled dusty plasma.
AB  - The collision between two counterpropagating dust acoustic solitary waves in a
      strongly coupled dusty plasma has been observed. The measured velocity and width
      of the solitary wave agree with the solution of the Korteweg-de Vries equation
      derived by using the generalized hydrodynamic model. The two counterpropagating
      solitary waves of equal amplitude merge into a single pulse with twice the
      individual soliton amplitude and then pass through each other. The solitons
      suffer a small time delay in propagation after collision. The measured delay time
      obtained from their trajectories is also presented. 

PMID- 24580350
TI  - Localized transversal-rotational modes in linear chains of equal masses.
AB  - The propagation and localization of transversal-rotational waves in a two
      dimensional granular chain of equal masses are analyzed in this study. The masses
      are infinitely long cylinders possessing one translational and one rotational
      degree of freedom. Two dispersive propagating modes are predicted in this
      granular crystal. By considering the semi-infinite chain with a boundary
      condition applied at its beginning, the analytical study demonstrates the
      existence of localized modes, each mode composed of two evanescent modes. Their
      existence, position (either in the gap between the propagating modes or in the
      gap above the upper propagating mode), and structure of spatial localization are
      analyzed as a function of the relative strength of the shear and bending
      interparticle interactions and for different boundary conditions. This
      demonstrates the existence of a localized mode in a semi-infinite monatomic chain
      when transversal-rotational waves are considered, while it is well known that
      these types of modes do not exist when longitudinal waves are considered. 

PMID- 24580351
TI  - Radiation of charges moving along the boundary of a wire metamaterial.
AB  - The electromagnetic fields of charges moving along the boundary of a "wire
      metamaterial" perpendicularly to the wires are investigated. The metamaterial
      under consideration represents a volume-periodic structure of thin parallel wires
      located in a square lattice. This structure is described by an effective
      permittivity tensor and exhibits both spatial and frequency dispersion. It is
      shown that the charge generates nondivergent radiation, as in the case of an
      infinite metamaterial. However, unlike the infinite-metamaterial case, the
      radiation concentrates near a certain plane (not line) behind the charge, and it
      is asymmetric with respect to this plane. An algorithm for calculating the wave
      fields of finite-length bunches is developed, and some typical numerical results
      are given. They demonstrate that the structure under consideration can be applied
      to determine the size and form of such bunches. The stopping and deflection
      forces acting on the charge are also calculated. 

PMID- 24580352
TI  - Frequency effects on the scale and behavior of acoustic streaming.
AB  - Acoustic streaming underpins an exciting range of fluid manipulation phenomena of
      rapidly growing significance in microfluidics, where the streaming often assumes
      the form of a steady, laminar jet emanating from the device surface, driven by
      the attenuation of acoustic energy within the beam of sound propagating through
      the liquid. The frequencies used to drive such phenomena are often chosen ad hoc
      to accommodate fabrication and material issues. In this work, we seek a better
      understanding of the effects of sound frequency and power on acoustic streaming.
      We present and, using surface acoustic waves, experimentally verify a laminar jet
      model that is based on the turbulent jet model of Lighthill, which is appropriate
      for acoustic streaming seen at micro- to nanoscales, between 20 and 936 MHz and
      over a broad range of input power. Our model eliminates the critically
      problematic acoustic source singularity present in Lighthill's model, replacing
      it with a finite emission area and enabling determination of the streaming
      velocity close to the source. At high acoustic power P (and hence high jet
      Reynolds numbers ReJ associated with fast streaming), the laminar jet model
      predicts a one-half power dependence (U~P1/2~ ReJ) similar to the turbulent jet
      model. However, the laminar model may also be applied to jets produced at low
      powers-and hence low jet Reynolds numbers ReJ-where a linear relationship between
      the beam power and streaming velocity exists: U~P~ReJ2. The ability of the
      laminar jet model to predict the acoustic streaming behavior across a broad range
      of frequencies and power provides a useful tool in the analysis of microfluidics
      devices, explaining peculiar observations made by several researchers in the
      literature. In particular, by elucidating the effects of frequency on the scale
      of acoustically driven flows, we show that the choice of frequency is a vitally
      important consideration in the design of small-scale devices employing acoustic
      streaming for microfluidics. 

PMID- 24580353
TI  - Stationary solutions for the 1+1 nonlinear Schrodinger equation modeling
      attractive Bose-Einstein condensates in small potentials.
AB  - Stationary solutions for the 1+1 cubic nonlinear Schrodinger equation (NLS)
      modeling attractive Bose-Einstein condensates (BECs) in a small potential are
      obtained via a form of nonlinear perturbation. The focus here is on perturbations
      to the bright soliton solutions due to small potentials which either confine or
      repel the BECs: under arbitrary piecewise continuous potentials, we obtain the
      general representation for the perturbation theory of the bright solitons.
      Importantly, we do not need to assume that the nonlinearity is small, as we
      perform a sort of nonlinear perturbation by allowing the zeroth-order
      perturbation term to be governed by a nonlinear equation. This is useful, in that
      it allows us to consider perturbations of bright solitons of arbitrary size. In
      some cases, exact solutions can be recovered, and these agree with known results
      from the literature. Several special cases are considered which involve confining
      potentials of specific relevance to BECs. We make several observations on the
      influence of the small potentials on the behavior of the perturbed bright
      solitons. The results demonstrate the difference between perturbed bright
      solitons in the attractive NLS and those results found in the repulsive NLS for
      dark solitons, as discussed by Mallory and Van Gorder, [Phys. Rev. E 88 013205
      (2013)]. Extension of these results to more spatial dimensions is mentioned.

PMID- 24580354
TI  - Langevin dynamics in inhomogeneous media: re-examining the Ito-Stratonovich
      dilemma.
AB  - The diffusive dynamics of a particle in a medium with space-dependent friction
      coefficient is studied within the framework of the inertial Langevin equation. In
      this description, the ambiguous interpretation of the stochastic integral, known
      as the Ito-Stratonovich dilemma, is avoided since all interpretations converge to
      the same solution in the limit of small time steps. We use a newly developed
      method for Langevin simulations to measure the probability distribution of a
      particle diffusing in a flat potential. Our results reveal that both the Ito and
      Stratonovich interpretations converge very slowly to the uniform equilibrium
      distribution for vanishing time step sizes. Three other conventions exhibit
      significantly improved accuracy: (i) the "isothermal" (Hanggi) convention, (ii)
      the Stratonovich convention corrected by a drift term, and (iii) a newly proposed
      convention employing two different effective friction coefficients representing
      two different averages of the friction function during the time step. We argue
      that the most physically accurate dynamical description is provided by the third
      convention, in which the particle experiences a drift originating from the
      dissipation instead of the fluctuation term. This feature is directly related to
      the fact that the drift is a result of an inertial effect that cannot be well
      understood in the Brownian, overdamped limit of the Langevin equation. 

PMID- 24580355
TI  - Numerical method for the stochastic projected Gross-Pitaevskii equation.
AB  - We present a method for solving the stochastic projected Gross-Pitaevskii
      equation (SPGPE) for a three-dimensional weakly interacting Bose gas in a
      harmonic-oscillator trapping potential. The SPGPE contains the challenge of both
      accurately evolving all modes in the low-energy classical region of the system,
      and evaluating terms from the number-conserving scattering reservoir process. We
      give an accurate and efficient procedure for evaluating the scattering terms
      using a Hermite-polynomial based spectral-Galerkin representation, which allows
      us to precisely implement the low-energy mode restriction. Stochastic integration
      is performed using the weak semi-implicit Euler method. We extensively
      characterize the accuracy of our method, finding a faster-than-expected rate of
      stochastic convergence. Physical consistency of the algorithm is demonstrated by
      considering thermalization of initially random states. 

PMID- 24580356
TI  - Estimating the effective Reynolds number in implicit large-eddy simulation.
AB  - In implicit large-eddy simulation (ILES), energy-containing large scales are
      resolved, and physics capturing numerics are used to spatially filter out
      unresolved scales and to implicitly model subgrid scale effects. From an applied
      perspective, it is highly desirable to estimate a characteristic Reynolds number
      (Re)-and therefore a relevant effective viscosity-so that the impact of
      resolution on predicted flow quantities and their macroscopic convergence can
      usefully be characterized. We argue in favor of obtaining robust Re estimates
      away from the smallest scales of the simulated flow-where numerically controlled
      dissipation takes place and propose a theoretical basis and framework to
      determine such measures. ILES examples include forced turbulence as a steady flow
      case, the Taylor-Green vortex to address transition and decaying turbulence, and
      simulations of a laser-driven reshock experiment illustrating a fairly complex
      turbulence problem of current practical interest. 

PMID- 24580357
TI  - Coarse-grained particle model for pedestrian flow using diffusion maps.
AB  - Interacting particle systems constitute the dynamic model of choice in a variety
      of application areas. A prominent example is pedestrian dynamics, where good
      design of escape routes for large buildings and public areas can improve
      evacuation in emergency situations, avoiding exit blocking and the ensuing panic.
      Here we employ diffusion maps to study the coarse-grained dynamics of two
      pedestrian crowds trying to pass through a door from opposite sides. These
      macroscopic variables and the associated smooth embeddings lead to a better
      description and a clearer understanding of the nature of the transition to
      oscillatory dynamics. We also compare the results to those obtained through
      intuitively chosen macroscopic variables. 

PMID- 24580358
TI  - Stable-phase method for hierarchical annealing in the reconstruction of porous
      media images.
AB  - In this paper, we introduce a stable-phase approach for hierarchical annealing
      which addresses the very large computational costs associated with simulated
      annealing for the reconstruction of large-scale binary porous media images. Our
      presented method, which uses the two-point correlation function as the
      morphological descriptor, involves the reconstruction of three-phase and two
      phase structures. We consider reconstructing the three-phase structures based on
      standard annealing and the two-phase structures based on standard and
      hierarchical annealings. From the result of the two-dimensional (2D)
      reconstruction, we find that the 2D generation does not fully capture the
      morphological information of the original image, even though the two-point
      correlation function of the reconstruction is in excellent agreement with that of
      the reference image. For the reconstructed three-dimensional (3D) microstructure,
      we calculate its permeability and compare it to that of the reference 3D
      microstructure. The result indicates that the reconstructed structure has a lower
      degree of connectedness than that of the actual sandstone. We also compare the
      computation time of our presented method to that of the standard annealing, which
      shows that our presented method of orders of magnitude improves the convergence
      rate. That is because only a small part of the pixels in the overall hierarchy
      need to be considered for sampling by the annealer. 

PMID- 24580359
TI  - Modeling of nonlinear optical activity in propagation of ultrashort elliptically
      polarized laser pulses.
AB  - We propose a general model of third-order nonlinear optical susceptibility of
      isotropic gyrotropic medium with frequency and spatial dispersion. Our model
      allows for the description of the propagation of ultrashort (several
      oscillations) elliptically polarized laser pulses in such a medium and does not
      require smallness of the characteristic nonlocality dimension, unlike the
      conventional phenomenological model. We implemented our model numerically by
      means of a modified finite-difference time-domain method with an auxiliary
      differential equation. We have validated the correctness of our model by the
      comparison of the results obtained in our numerical simulations with generally
      known effects observed experimentally and described earlier theoretically for the
      monochromatic radiation or within the slowly varying envelope approach. We
      investigated effects accompanying the propagation of ultrashort (several
      oscillations) light pulses in nonlinear isotropic gyrotropic medium with
      frequency and spatial dispersion of cubic nonlinearity. 

PMID- 24580360
TI  - Polar-coordinate lattice Boltzmann modeling of compressible flows.
AB  - We present a polar coordinate lattice Boltzmann kinetic model for compressible
      flows. A method to recover the continuum distribution function from the discrete
      distribution function is indicated. Within the model, a hybrid scheme being
      similar to, but different from, the operator splitting is proposed. The temporal
      evolution is calculated analytically, and the convection term is solved via a
      modified Warming-Beam (MWB) scheme. Within the MWB scheme a suitable switch
      function is introduced. The current model works not only for subsonic flows but
      also for supersonic flows. It is validated and verified via the following well
      known benchmark tests: (i) the rotational flow, (ii) the stable shock tube
      problem, (iii) the Richtmyer-Meshkov (RM) instability, and (iv) the Kelvin
      Helmholtz instability. As an original application, we studied the nonequilibrium
      characteristics of the system around three kinds of interfaces, the shock wave,
      the rarefaction wave, and the material interface, for two specific cases. In one
      of the two cases, the material interface is initially perturbed, and consequently
      the RM instability occurs. It is found that the macroscopic effects due to
      deviating from thermodynamic equilibrium around the material interface differ
      significantly from those around the mechanical interfaces. The initial
      perturbation at the material interface enhances the coupling of molecular motions
      in different degrees of freedom. The amplitude of deviation from thermodynamic
      equilibrium around the shock wave is much higher than those around the
      rarefaction wave and material interface. By comparing each component of the high
      order moments and its value in equilibrium, we can draw qualitatively the main
      behavior of the actual distribution function. These results deepen our
      understanding of the mechanical and material interfaces from a more fundamental
      level, which is indicative for constructing macroscopic models and other kinds of
      kinetic models. 

PMID- 24580361
TI  - Tensor renormalization group study of classical XY model on the square lattice.
AB  - Using the tensor renormalization group method based on the higher-order singular
      value decomposition, we have studied the thermodynamic properties of the
      continuous XY model on the square lattice. The temperature dependence of the free
      energy, the internal energy, and the specific heat agree with the Monte Carlo
      calculations. From the field dependence of the magnetic susceptibility, we find
      the Kosterlitz-Thouless transition temperature to be 0.8921(19), consistent with
      the Monte Carlo as well as the high temperature series expansion results. At the
      transition temperature, the critical exponent delta is estimated as 14.5, close
      to the analytic value by Kosterlitz. 

PMID- 24580362
TI  - Alternative curved-boundary treatment for the lattice Boltzmann method and its
      application in simulation of flow and potential fields.
AB  - Since the lattice Boltzmann method originally carries out the simulations on the
      regular Cartesian lattices, curved boundaries are often approximated as a series
      of stair steps. The most commonly employed technique for resolving curved
      boundary problems is extrapolating or interpolating macroscopic properties of
      boundary nodes. Previous investigations have indicated that using more than one
      equation for extrapolation or interpolation in boundary conditions potentially
      causes abrupt changes in particle distributions. Therefore, a curved-boundary
      treatment is introduced to improve computational accuracy of the conventional
      stair-shaped approximation used in lattice Boltzmann simulations by using a
      unified equation for extrapolation of macroscopic variables. This boundary
      condition is not limited to fluid flow and can be extended to potential fields.
      The proposed treatment is tested against several well-established problems and
      the solutions order of accuracy is evaluated. Numerical results show that the
      present treatment is of second-order accuracy and has reliable stability
      characteristics. 

PMID- 24580363
TI  - Impact of contrarians and intransigents in a kinetic model of opinion dynamics.
AB  - In this work we study opinion formation on a fully connected population
      participating of a public debate with two distinct choices, where the agents may
      adopt three different attitudes (favorable to either one choice or to the other,
      or undecided). The interactions between agents occur by pairs and are
      competitive, with couplings that are either negative with probability p or
      positive with probability 1-p. This bimodal probability distribution of couplings
      produces a behavior similar to the one resulting from the introduction of Galam's
      contrarians in the population. In addition, we consider that a fraction d of the
      individuals are intransigent, that is, reluctant to change their opinions. The
      consequences of the presence of contrarians and intransigents are studied by
      means of computer simulations. Our results suggest that the presence of
      inflexible agents affects the critical behavior of the system, causing either the
      shift of the critical point or the suppression of the ordering phase transition,
      depending on the groups of opinions to which the intransigents belong. We also
      discuss the relevance of the model for real social systems. 

PMID- 24580364
TI  - Wang-Landau sampling with logarithmic windows for continuous models.
AB  - We present a modified Wang-Landau sampling (MWLS) for continuous statistical
      models by partitioning the energy space into a set of windows with
      logarithmically shrinking width. To demonstrate its necessity and advantages, we
      apply this sampling to several continuous models, including the two-dimensional
      square XY spin model, triangular J1-J2 spin model, and Lennard-Jones cluster
      model. Given a finite number of bins for partitioning the energy space, the
      conventional Wang-Landau sampling may not generate sufficiently accurate density
      of states (DOS) around the energy boundaries. However, it is demonstrated that
      much more accurate DOS can be obtained by this MWLS, and thus a precise
      evaluation of the thermodynamic behaviors of the continuous models at extreme low
      temperature (kBT<0.1) becomes accessible. The present algorithm also allows
      efficient computation besides the highly reliable data sampling. 

PMID- 24580365
TI  - Robust computation of dipole electromagnetic fields in arbitrarily anisotropic,
      planar-stratified environments.
AB  - We develop a general-purpose formulation, based on two-dimensional spectral
      integrals, for computing electromagnetic fields produced by arbitrarily oriented
      dipoles in planar-stratified environments, where each layer may exhibit arbitrary
      and independent anisotropy in both its (complex) permittivity and permeability
      tensors. Among the salient features of our formulation are (i) computation of
      eigenmodes (characteristic plane waves) supported in arbitrarily anisotropic
      media in a numerically robust fashion, (ii) implementation of an hp-adaptive
      refinement for the numerical integration to evaluate the radiation and weakly
      evanescent spectra contributions, and (iii) development of an adaptive extension
      of an integral convergence acceleration technique to compute the strongly
      evanescent spectrum contribution. While other semianalytic techniques exist to
      solve this problem, none have full applicability to media exhibiting arbitrary
      double anisotropies in each layer, where one must account for the whole range of
      possible phenomena (e.g., mode coupling at interfaces and nonreciprocal mode
      propagation). Brute-force numerical methods can tackle this problem but only at a
      much higher computational cost. The present formulation provides an efficient and
      robust technique for field computation in arbitrary planar-stratified
      environments. We demonstrate the formulation for a number of problems related to
      geophysical exploration. 

PMID- 24580366
TI  - Characterization of local complex structures in a recurrence plot to improve
      nonlinear dynamic discriminant analysis.
AB  - Structures in recurrence plots (RPs), preserving the rich information of
      nonlinear invariants and trajectory characteristics, have been increasingly
      analyzed in dynamic discrimination studies. The conventional analysis of RPs is
      mainly focused on quantifying the overall diagonal and vertical line structures
      through a method, called recurrence quantification analysis (RQA). This study
      extensively explores the information in RPs by quantifying local complex RP
      structures. To do this, an approach was developed to analyze the combination of
      three major RQA variables: determinism, laminarity, and recurrence rate (DLR) in
      a metawindow moving over a RP. It was then evaluated in two experiments
      discriminating (1) ideal nonlinear dynamic series emulated from the Lorenz system
      with different control parameters and (2) data sets of human heart rate
      regulations with normal sinus rhythms (n = 18) and congestive heart failure (n =
      29). Finally, the DLR was compared with seven major RQA variables in terms of
      discriminatory power, measured by standardized mean difference (DSMD). In the two
      experiments, DLR resulted in the highest discriminatory power with DSMD = 2.53
      and 0.98, respectively, which were 7.41 and 2.09 times the best performance from
      RQA. The study also revealed that the optimal RP structures for the
      discriminations were neither typical diagonal structures nor vertical structures.
      These findings indicate that local complex RP structures contain some rich
      information unexploited by RQA. Therefore, future research to extensively analyze
      complex RP structures would potentially improve the effectiveness of the RP
      analysis in dynamic discrimination studies. 

PMID- 24580367
TI  - Reduction of adenovirus 36-induced obesity and inflammation by mulberry extract.
AB  - Adenovirus 36 (Ad36) is known to be associated with human obesity and to trigger
      inflammation in murine models. However, to date no clinical drugs for treating
      virus-induced obesity have been developed. Therefore, in this study, the anti
      obesity and anti-inflammation effects of mulberry extract on Ad36 were evaluated
      in mice. The mulberry extract-fed group showed a reduction in total body weight
      and in epidermal fat pads. A combination of various mulberry components (1
      deoxynojirimycin, kuromanin chloride and resveratrol) and a mulberry extract
      prevented viral replication by 50% and 70%, respectively, compared with an
      untreated Ad36-infected group. Moreover, the extract decreased both
      concentrations of proinflammatory cytokines, such as MCP-1 and TNF-alpha, and the
      numbers of infiltrating immune cells and macrophages in epidermal fat pads. In
      conclusion, dietary mulberry extract might offer an avenue for the development of
      therapeutic approaches for treating or preventing virus-induced obesity and
      inflammation-related metabolic diseases. 

PMID- 24580368
TI  - Technique to facilitate the native valve reimplantation during the david
      procedure.
AB  - The reimplantation technique for valve-sparing aortic root replacement is
      increasingly used to treat aortic root pathology. The systematic approach
      described by El Khoury in 2009 and modified in 2011 using the Valsava graft is
      simple and reproducible. However, in-conduit suturing of the aortic valve annulus
      and small rim of sinus remnant to the graft sinuses is time-consuming and may
      lead to bleeding or distortion of the prosthetic root. We describe a simple
      technique to facilitate the native valve reimplantation.

PMID- 24580369
TI  - Patients' beliefs and behaviors related to treatment adherence in patients with
      asthma requiring maintenance treatment in Asia.
AB  - OBJECTIVES: To identify patients' beliefs or behaviors related to treatment
      adherence and to assess association between asthma control and adherence in Asian
      patients with asthma. METHODS: We conducted a cross-sectional observational study
      of adult patients with asthma from specialist clinics in six Asian countries.
      Patients who were deemed by their treating physicians to require a maintenance
      treatment with an inhaler for at least 1 year were recruited. Patients completed
      a 12-item questionnaire related to health beliefs and behaviors, the 8-item
      Morisky Medication Adherence Scale (MMAS-8), the Asthma Control Test (ACTTM), and
      the Standardized Asthma Quality of Life Questionnaire (AQLQ-S). RESULTS: Of the
      1054 patients recruited, 99% were current users of inhaled corticosteroids. The
      mean ACT score was 20.0 +/- 4.5 and 64% had well-controlled asthma. The mean MMAS
      8 score was 5.5 +/- 2.0 and 53% were adherent. Adherence was significantly
      associated with patients' understanding of the disease and inhaler techniques,
      and with patients' acceptance of inhaler medicines in terms of benefits, safety,
      convenience, and cost (p < 0.01 for all). In multivariate analysis, three
      questions related to patients' acceptance of inhaler medicines remained
      significantly associated with poor adherence, after adjusting for potential
      confounders: "I am not sure inhaler type medicines work well" (p = 0.001),
      "Taking medicines more than once a day is inconvenient" (p = 0.002), and
      "Sometimes I skip my inhaler to use it over a longer period" (p < 0.001).
      CONCLUSIONS: Our study showed that patients' acceptance of the benefits,
      convenience and cost of inhaler medications have a significant impact on
      treatment adherence in the participating Asian countries.

PMID- 24580370
TI  - Validity and reliability of Physical Activity Enjoyment Scale questionnaire
      (PACES) in children with asthma.
AB  - OBJECTIVE: The aim of this study is to test the psychometric properties of the
      Physical Activity Enjoyment Scale (PACES) in children with asthma. METHOD:
      Participants included 185 children (age = 11.38 +/- 1.12 years; body mass index =
      20.66 +/- 4.13 kg/m(2)): 107 children with asthma and 78 healthy children. To
      test the enjoyment of physical activity, PACES of Motl et al. was used in its
      Spanish version. In addition, the Physical Activity Questionnaire for Children
      (PAQ-C), Paediatric Asthma Quality of Life Questionnaire (PAQLQ) and Physical
      Self-Concept Questionnaire (CAF) have been used. RESULTS: The results have shown
      a two-factor structure corresponding to the model whose settings have been good.
      PACES internal consistency was very high (Cronbach's alpha = 0.906). The PACES
      test-retest reliability indicates a good temporal concordance (Spearman rho =
      0.868, p < 0.001). This presents an adequate concurrent validity with the total
      PAQLQ, the PAQ-C as well as with ability, fitness, attractiveness, strength and
      general physical self-concept. CONCLUSIONS: The findings confirm that PACES is a
      valid and reliable measure of physical activity enjoyment in children with
      asthma.

PMID- 24580371
TI  - OX40 ligand: a potential costimulatory molecule in atopic asthma.
AB  - OBJECTIVE: We aimed to assess the percentage of peripheral blood B-lymphocytes
      expressing OX40 ligand (OX40L) in adult atopic and non-atopic asthmatic patients,
      and in healthy controls. METHODS: This case-control study included 15 atopic
      asthmatic patients, 15 non-atopic asthmatic patients, and 15 healthy controls.
      Atopic status was determined by skin prick test reaction to the most common
      locally-encountered allergens. For all subjects, pulmonary function tests and
      measurement of total serum immunoglobulin E (IgE) levels by ELISA were performed.
      In addition, the percentage of B-lymphocytes expressing OX40L was assessed by
      flow cytometry in all three groups. RESULTS: OX40L expression was significantly
      higher in atopic asthmatics than in non-atopic asthmatics and controls, but did
      not differ significantly between non-atopic asthmatics or controls. Among atopic
      asthmatics, OX40L expression correlated positively with total serum IgE levels,
      but not with age, disease duration, or values of forced expiratory volume in the
      first second. CONCLUSION: The over-expression of OX40L in atopic asthmatic
      patients appears to be linked to markers of the atopic status as total serum IgE,
      and signifies the vital role of OX40L in the atopic mechanism. Further large
      scale studies are needed to investigate the role of OX40L in other atopic
      diseases and its relation to disease activity and severity.

PMID- 24580372
TI  - Preventive asthma medication discontinuation among children enrolled in fee-for
      service Medicaid.
AB  - OBJECTIVE: Local-area studies demonstrate that preventive asthma medication
      discontinuation among Medicaid and Children's-Health-Insurance-Program (CHIP)
      enrolled children leads to adverse outcomes. We assessed time-to-discontinuation
      for preventive asthma medication and its risk factors among fee-for-service
      Medicaid/CHIP child beneficiaries. METHODS: National-Health-Interview-Survey
      participants (1997-2005) with >=1 Medicaid- or CHIP-paid claims when 2-17 years
      old (n = 4262) were linked to Medicaid-Analytic-eXtract claims (1999-2008).
      Multivariate Cox proportional-hazards models to assess time-to-discontinuation
      (i.e. failing to refill prescriptions <30 d after previous supplies ran out)
      included demographic factors and medication regimen (inhaled corticosteroids
      [ICS], long-acting beta2-agonists, leukotriene modifiers, mast cell stabilizers,
      and monoclonal antibodies). RESULTS: Sixty-three percent discontinued preventive
      asthma medications by 90 d after the first prescription. Adolescents and toddlers
      had slightly higher hazards of discontinuation (adjusted hazard ratios [aHR],
      1.13; 95% CI, 1.05-1.23; and 1.12; 1.03-1.21, respectively) versus 5-11-year
      olds, as did Hispanics (aHR, 1.24; 1.13-1.35) and non-Hispanic blacks (aHR, 1.17;
      1.07-1.28) versus non-Hispanic whites, children in households with one adult and
      >=3 children (aHR, 1.17; 1.05-1.30) versus multiple adults and <=2 children, and
      children with caregivers' educational-attainment <=12th grade (aHR, 1.11; 1.02
      1.20) versus caregivers with some college. Compared to regimens including both
      ICS and leukotriene modifiers, discontinuation was greater for those on ICS
      without leukotriene modifiers or on other preventive asthma medications (aHR,
      1.67; 1.56-1.80; and 2.23; 1.78-2.80, respectively). CONCLUSION: More than 60% of
      children enrolled in fee-for-service Medicaid/CHIP discontinued preventive asthma
      medications by 90 d. Risk was increased for minorities and children from
      disadvantaged households. Understanding these factors may inform future pediatric
      asthma guidelines.

PMID- 24580373
TI  - Influence of an inner-sphere K+ ion on the magnetic behavior of N2(3-) radical
      bridged dilanthanide complexes isolated using an external magnetic field.
AB  - The synthesis and full magnetic characterization of a new series of N2(3-)
      radical-bridged lanthanide complexes [{(R2N)2(THF)Ln}2(MU3-eta(2):eta(2):eta(2)
      N2)K] [1-Ln; Ln = Gd, Tb, Dy; NR2 = N(SiMe3)2] are described for comprehensive
      comparison with the previously reported series [K(18-crown
      6)(THF)2]{[(R2N)2(THF)Ln]2(MU-eta(2):eta(2)-N2)} (2-Ln; Ln = Gd, Tb, Dy).
      Structural characterization of 1-Ln crystals grown with the aid of a Nd2Fe13B
      magnet reveals inner-sphere coordination of the K(+) counterion within 2.9 A of
      the N2(3-) bridge, leading to bending of the planar Ln-(N2(3-))-Ln unit present
      in 2-Ln. Direct current (dc) magnetic susceptibility measurements performed on 1
      Gd reveal antiferromagnetic coupling between the Gd(III) centers and the N2(3-)
      radical bridge, with a strength matching that obtained previously for 2-Gd at J ~
      -27 cm(-1). Unexpectedly, however, a competing antiferromagnetic Gd(III)-Gd(III)
      exchange interaction with J ~ -2 cm(-1) also becomes prominent, dramatically
      changing the magnetic behavior at low temperatures. Alternating current (ac)
      magnetic susceptibility characterization of 1-Tb and 1-Dy demonstrates these
      complexes to be single-molecule magnets under zero applied dc field, albeit with
      relaxation barriers (Ueff = 41.13(4) and 14.95(8) cm(-1), respectively) and
      blocking temperatures significantly reduced compared to 2-Tb and 2-Dy. These
      differences are also likely to be a result of the competing antiferromagnetic
      Ln(III)-Ln(III) exchange interactions of the type quantified in 1-Gd. 

PMID- 24580374
TI  - How accurate are Americans' perceptions of their own weight?
AB  - As obesity/overweight has increased in the United States (Centers for Disease
      Control and Prevention, 2009 ), studies have found that Americans' perceptions of
      their own weight often are not aligned with their actual body mass index (BMI;
      Brener et al., 2004 ; Christakis, 2003; Johnson-Taylor et al., 2008 ). Taylor,
      Funk, and Craighill ( 2006 ) found that half of Americans whose BMI indicated
      they were overweight perceived their weight to be just about right. The purpose
      of this study was to examine factors that influence the accuracy of weight self
      perceptions and whether accuracy influences health behaviors. Using data from the
      2007 Health Information National Trends Survey, the authors compared respondents'
      weight self-perceptions to their actual BMI to determine the accuracy of their
      weight self-perceptions. About 28%of respondents were obese, 35%were overweight,
      35%were of normal weight, and 2%were underweight. About three quarters of the
      sample's self-perceptions of weight were aligned with their BMI. About 10%of the
      sample had a BMI that indicated they were overweight, but they perceived
      themselves to be of normal weight; about 10%were of normal weight but perceived
      themselves to be overweight; and about 5%of respondents were of normal weight but
      thought they were underweight. Gender, race, and education were associated with
      the accuracy of respondents' weight perceptions. Results suggest that asking
      patients about their weight self-perceptions could be useful in clinical settings
      and that weight perception accuracy could be used to segment audiences and tailor
      messages. 

PMID- 24580375
TI  - Durable carbon-coated Li2(S) core-shell spheres for high performance
      lithium/sulfur cells.
AB  - Lithium sulfide (Li2S) is an attractive cathode material with a high theoretical
      specific capacity (1166 mAh g(-1)). However, the poor cycle life and rate
      capability have remained significant challenges, preventing its practical
      application. Here, Li2S spheres with size control have been synthesized for the
      first time, and a CVD method for converting them into stable carbon-coated Li2S
      core-shell (Li2S@C) particles has been successfully employed. These Li2S@C
      particles with protective and conductive carbon shells show promising specific
      capacities and cycling performance with a high initial discharge capacity of 972
      mAh g(-1) Li2S (1394 mAh g(-1) S) at the 0.2C rate. Even with no added carbon, a
      very high Li2S content (88 wt % Li2S) electrode composed of 98 wt % 1 MUm Li2S@C
      spheres and 2 wt % binder shows rather stable cycling performance, and little
      morphology change after 400 cycles at the 0.5C rate. 

PMID- 24580376
TI  - The personal myth: a re-evaluation.
AB  - This paper presents a re-evaluation of Kris's personal myth. The notion has been
      used rather sparingly despite the Delphi Symposium in 1984 on the question of its
      clinical usefulness. After framing the notion of myth, some difficulties related
      to the question are identified. A clinical vignette exemplifies some of the
      ambiguities in its definition but stresses its clinical relevance. A discussion
      expands on these situations so as to propose three various aspects of personal
      myths to account for the two variants identified by Kris. The actualization of
      the underlying fantasy in the character organization is a third form and the
      technical aspect associated with it is reviewed from a new perspective. The
      family romance is revisited to reassess its role as the basis of the personal
      myth in the face of studies favouring an earlier development of the myth. 

PMID- 24580377
TI  - Evaluating the feasibility and impact of an internet-based lifestyle management
      program in a diabetes care setting.
AB  - BACKGROUND: This study determined the impact of an online lifestyle management
      program on obese individuals with type 2 diabetes in a large academic diabetes
      clinic. SUBJECTS AND METHODS: Using a single cohort design, individuals with type
      2 diabetes and a body mass index (BMI) of >= 30 kg/m(2) were recruited to have
      access to the Virtual Lifestyle Management (VLM) program for 1 year, in addition
      to their routine care. Participants were assessed at baseline and at 6 and 12
      months for the following outcomes: (a) glycated hemoglobin (A1C), (b) lipids
      (total cholesterol [TC] and TC/high-density lipid [HDL] ratio), (c) weight, (d)
      BMI, and (e) body fat percentage (BFP). RESULTS: Seventy-eight individuals
      consented to the study, 66 (84%) logged onto the system two or more times, and 49
      (62%) contributed data at the 1-year program. At baseline, the mean age of
      participants was 57.9 years of age, and 52% were female. At 12 months, mean
      differences from baseline were as follows: A1C, -0.3% (95% confidence interval
      [CI] -0.1, -0.5; P<0.05); TC/HDL, -0.2 (95% CI -0.01, -0.04; P<0.05); weight, 
      8.6 pounds (95% CI -3.7, -13.6; P<0.05); BMI, -1.5 kg/m(2) (95% CI -0.7, -2.3;
      P<0.05); and BFP, -1.8% (95% CI -0.9, -2.7; P<0.05). After adjusting for program
      use, age, and sex, changes in BMI, BFP, and self-reported daily steps taken were
      statistically significant at 12 months. CONCLUSIONS: This before-after pilot
      study demonstrates that adding an Internet-based lifestyle modification program
      to usual care may improve clinically important outcomes.

PMID- 24580378
TI  - Effect of charge regulation and ion-dipole interactions on the selectivity of
      protein-nanoparticle binding.
AB  - We investigate the role of different mesoscopic interactions (Coulomb, charge
      regulation, and ion-dipole "surface patch" effects) on the binding of bovine
      serum albumin (BSA) and beta-lactoglobulin (BLG) to a cationic gold nanoparticle
      (TTMA+). The results demonstrate that the charge-regulation mechanism plays a
      vital role for selectivity of protein-nanoparticle complexation at low salt
      concentration. At slightly higher ionic strengths, charge-dipole effects are the
      dominating driving force. Thus, very small variations in salt concentration
      strongly influence the origin of complexation. 

PMID- 24580379
TI  - Exploring the validity of mild cognitive impairment (MCI) subtypes: multiple
      domain amnestic MCI is the only identifiable subtype at longitudinal follow-up.
AB  - BACKGROUND: Epidemiological research exploring risk factors for Alzheimer's
      dementia resulted in the identification of the mild cognitive impairment (MCI)
      profile. Subsequently, distinct subtypes of MCI have been proposed; however, the
      validity of these as diagnostic entities remains uncertain. DESIGN AND
      PARTICIPANTS: The aim of the present study was to examine the longitudinal
      neuropsychological profiles of MCI subtypes. A total of 118 adults aged 60-90
      years were classified at screening as amnestic (a-MCI), nonamnestic (na-MCI), and
      multiple-domain amnestic (a-MCI+) and were assessed at two time points across 20
      months on a comprehensive neuropsychological assessment battery. RESULTS: The a
      MCI+ group displayed the poorest performance of all groups in terms of episodic
      memory, working memory, attention, and executive functioning. CONCLUSIONS: These
      findings suggest that the a-MCI+ subtype is the only variant that is recognizable
      via neuropsychological testing. In contrast, the differentiation between single
      domain subtypes and healthy controls is difficult and may not be achievable
      through current neuropsychological assessment practices.

PMID- 24580380
TI  - Transition state in DNA polymerase beta catalysis: rate-limiting chemistry
      altered by base-pair configuration.
AB  - Kinetics studies of dNTP analogues having pyrophosphate-mimicking beta,gamma
      pCXYp leaving groups with variable X and Y substitution reveal striking
      differences in the chemical transition-state energy for DNA polymerase beta that
      depend on all aspects of base-pairing configurations, including whether the
      incoming dNTP is a purine or pyrimidine and if base-pairings are right (T*A and
      G*C) or wrong (T*G and G*T). Bronsted plots of the catalytic rate constant
      (log(kpol)) versus pKa4 for the leaving group exhibit linear free energy
      relationships (LFERs) with negative slopes ranging from -0.6 to -2.0, consistent
      with chemical rate-determining transition-states in which the active-site adjusts
      to charge-stabilization demand during chemistry depending on base-pair
      configuration. The Bronsted slopes as well as the intercepts differ dramatically
      and provide the first direct evidence that dNTP base recognition by the enzyme
      primer-template complex triggers a conformational change in the catalytic region
      of the active-site that significantly modifies the rate-determining chemical
      step. 

PMID- 24580382
TI  - Estimation of glomerular filtration rate to adjust vancomycin dosage in
      critically ill patients: superiority of the Chronic Kidney Disease Epidemiology
      Collaboration equation?
AB  - The purpose of this study was to determine the best estimate of glomerular
      filtration rate (GFR) to adjust vancomycin (VAN) dosage in critically ill
      patients. Seventy-eight adult intensive care unit patients received a 15 mg/kg
      loading dose of VAN plus a 30 mg/kg/day continuous infusion. Steady-state
      concentration was measured 48 hours later and the dose was adjusted to obtain a
      target concentration ranging from 20 to 25 mg/l. GFR was estimated by measured
      creatinine clearance (CLCR), Cockcroft, Modification of Diet in Renal Disease and
      Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations. The
      required dose providing the target concentration was 36+/-17 mg/kg/day. The first
      dosage had to be increased in 51% of all patients and in 84% of trauma patients
      (highest GFR), but had to be decreased in 17% of patients. The closest
      relationship between clearances of vancomycin was observed with CKD-EPI to GFR.
      The correlation between clearances of vancomycin and measured CLCR was
      significant but was rather poor with Cockcroft and Modification of Diet in Renal
      Disease equation. On the Bland and Altman plots, measured CLCR provided a lower
      bias but a larger confidence interval and a weaker precision than CKD-EPI. For
      VAN dose adjustments in intensive care unit patients, Cockcroft formula and
      Modification of Diet in Renal Disease should be used with caution. In clinical
      practice, the physician does not have at their disposal the patient's measured
      CLCR when prescribing. The CKD-EPI appears to be the best predictor of clearances
      of vancomycin for calculation of a therapeutic VAN regimen. 

PMID- 24580381
TI  - Nanoparticle-delivered transforming growth factor-beta siRNA enhances vaccination
      against advanced melanoma by modifying tumor microenvironment.
AB  - Achievement of potent immunoresponses against self/tumor antigens and effective
      therapeutic outcome against advanced tumors remain major challenges in cancer
      immunotherapy. The specificity and efficiency of two nanoparticle-based delivery
      systems, lipid-calcium-phosphate (LCP) nanoparticle (NP) and liposome-protamine
      hyaluronic acid (LPH) NP, provide us an opportunity to address both challenges. A
      mannose-modified LCP NP delivered both tumor antigen (Trp 2 peptide) and adjuvant
      (CpG oligonucleotide) to the dendritic cells and elicited a potent, systemic
      immune response regardless of the existence or the stage of tumors in the host.
      This vaccine was less effective, however, against later stage B16F10 melanoma in
      a subcutaneous syngeneic model. Mechanistic follow-up studies suggest that
      elevated levels of immune-suppressive cytokines within the tumor
      microenvironment, such as TGF-beta, might be responsible. We strategically
      augment the efficacy of LCP vaccine on an advanced tumor by silencing TGF-beta in
      tumor cells. The delivery of siRNA using LPH NP resulted in about 50% knockdown
      of TGF-beta in the late stage tumor microenvironment. TGF-beta down-regulation
      boosted the vaccine efficacy and inhibited tumor growth by 52% compared with
      vaccine treatment alone, as a result of increased levels of tumor infiltrating
      CD8+ T cells and decreased level of regulatory T cells. Combination of systemic
      induction of antigen-specific immune response with LCP vaccine and targeted
      modification of tumor microenvironment with LPH NP offers a flexible and powerful
      platform for both mechanism study and immunotherapeutic strategy development. 

PMID- 24580383
TI  - Low-dose epidural dexmedetomidine improves thoracic epidural anaesthesia for
      nephrectomy.
AB  - Thoracic epidural anaesthesia alone is an applied technique of anaesthesia for
      nephrectomy which has both advantages and limitations. Dexmedetomidine is a
      highly selective alpha2-adrenoreceptor agonist which has both central and
      peripheral analgesic properties. Forty patients undergoing nephrectomy were
      enrolled in this clinical trial and allocated randomly to two groups, a control
      group (C group) and a dexmedetomidine group (D group). The C group received
      epidural 0.75% levobupivacaine 12 ml with 1 ml of isotonic sodium chloride
      solution, while the D group received epidural 0.75% levobupivacaine 12 ml with 1
      ml (0.5 ug/kg) of dexmedetomidine. Haemodynamic changes, onset time and duration
      of sensory and motor block, muscle relaxation score, verbal rating score for
      pain, sedation score and the total postoperative analgesic consumption were
      evaluated. Sensory blockade duration was longer in the D group than in the C
      group (P=0.01). The incidence of motor block and the muscle relaxation score were
      significantly higher in the D group compared with the C group (P=0.01). Compared
      with the C group, pain scores were significantly lower in the first four
      postoperative hours in the D group (two hours rest P=0.038; two hours activity
      P=0.009; four hours rest P=0.044; four hours activity P=0.003). The total amount
      of flurbiprofen analgesic was significantly lower in the D group compared with
      the C group (P=0.03). Epidural dexmedetomidine 0.5 ug/kg appears to intensify
      thoracic epidural anaesthesia with levobupivacaine.

PMID- 24580384
TI  - A randomised controlled trial of ultrasound-assisted spinal anaesthesia.
AB  - Pre-procedural ultrasound scanning has been used to facilitate spinal anaesthesia
      in patients with difficult anatomical landmarks and shown to improve first
      attempt success rates in some studies. We studied whether pre-procedural
      ultrasound scanning improved first-attempt success rate and decreased time taken
      for the procedure in the general adult population. In this prospective,
      randomised controlled trial, 170 American Society of Anesthesiologists 1 to 3
      patients aged between 21 and 80 years were recruited. Informed consent was
      obtained. Patients were randomised into two groups, ultrasound-guided
      identification of landmarks (Ultrasound Group) and manual palpation of landmarks
      (Manual Palpation Group). The primary outcome was first-attempt success rate and
      secondary outcomes were time taken to perform procedure, number of needle
      redirections, patient satisfaction and complications. The first-attempt success
      rate was 64% in the Ultrasound Group and 52% in the Manual Palpation Group
      (P=0.16). Time taken for procedure was shorter in the Ultrasound Group compared
      to the Manual Palpation Group (2.9+/-3.6 minutes versus 3.9+/-3.7 min, P= 0.007).
      Patient satisfaction was higher in the Ultrasound Group. There were no
      differences in complications. As there was no statistically significant
      difference in first-attempt success rates between the two groups, existing
      evidence for routine pre-procedural scanning for all patients is inadequate. The
      current use of pre-procedural ultrasound scanning will probably be limited to
      selected patients where spinal anaesthesia may be technically challenging with
      conventional methods. 

PMID- 24580386
TI  - The effect of high-fidelity simulation on the confidence and decision-making
      ability of anaesthesia trainees in managing subsequent simulated 'can't intubate,
      can't oxygenate' scenarios.
AB  - The decision to attempt a percutaneous airway in a recognised 'Can't Intubate,
      Can't Oxygenate' (CICO) situation may occur too late to avoid a poor outcome. Our
      study was designed to investigate the effect of high-fidelity simulation on the
      confidence and decision-making ability of anaesthesia trainees in managing CICO
      scenarios in subsequent simulation. Nine anaesthesia trainees from Logan Hospital
      participated. Pre-study questionnaires surveying confidence levels in various
      anaesthetic crises were completed. All participants underwent an education
      session based on algorithms developed for failed intubation and ventilation, and
      techniques for securing percutaneous airway access. However, only four of the
      nine participated in a high-fidelity simulation session. All nine participants
      were then filmed during 'mini-simulation' assessment sessions and completed post
      study questionnaires identical to those at the commencement of the study. The
      four trainees who had undertaken the initial high-fidelity simulation had a lower
      median time to laryngeal mask airway attempt (60 versus 115 seconds) and time to
      percutaneous airway attempt (111 versus 172 seconds) in the subsequent
      simulation. The median number of deviations from the Difficult Airway Society
      algorithm was 0 for the simulation group compared to 1 for the non-simulation
      group. This small study suggests that high-fidelity simulation shortens the
      decision-making time of anaesthesia trainees in subsequent simulated CICO
      scenarios. This observation warrants follow-up in larger prospective trials. 

PMID- 24580385
TI  - Comparison of a Trigger Tool and voluntary reporting to identify adverse events
      in a paediatric intensive care unit.
AB  - Reduction of adverse events depends on accurate detection. The utility of a
      Trigger Tool to detect and classify severity of adverse events in an intensive
      care unit of a paediatric university hospital was compared to voluntary
      reporting. Sixty patient records were randomly selected from 314 admissions over
      three months. Events detected by the Trigger Tool were classified by two
      independent investigators as insignificant, minor, moderate, major or
      catastrophic. Examination of each record required, on average, 40 minutes. Ninety
      eight adverse events (1.66/patient) were detected in 59 available records. Mean
      admission was 2.77 days. The incidence of adverse events was 59.9 per 100 patient
      days or 0.60 events per patient per day. The number of events detected by the
      Trigger Tool was related to duration of admission (r=0.70, P <0.0001) and risk of
      mortality on admission (r=0.50, P=0.0001) but not to age. The inter-rater
      agreement on detection of adverse events was good. Investigator One detected 66
      adverse events while Investigator Two detected 93 events (kappa 0.63). Of the 61
      events detected by both investigators, the agreement of classification of
      severity was very good (kappa 0.89). Of the 56 events rated similarly by both
      investigators, 13 (23%) were insignificant, 19 (34%) were minor, 17 (30%) were
      moderate, 4 (7%) were major and 3 (6%) were catastrophic. Only four adverse
      events had been reported voluntarily, of which two were detected using the
      Trigger Tool. Whereas the Trigger Tool is a simple, efficient and robust method,
      voluntary reporting is inadequate and captures very few adverse events in the
      intensive care unit environment. 

PMID- 24580387
TI  - The epidemiology of adult Rapid Response Team patients in Australia.
AB  - Rapid Response Teams (RRT) are specialised teams that review deteriorating ward
      patients in an attempt to prevent morbidity and mortality. Most studies have
      assessed the effect of implementing an RRT into a hospital. There is much less
      literature on the characteristics and outcomes of RRT patients themselves. This
      article reviews the epidemiology of adult RRT patients in Australia and proposes
      three models of RRT syndromes. The number of RRT calls varies considerably in
      Australian hospitals from 1.35 to 71.3/1000 hospital admissions. Common causes of
      RRT calls include sepsis, atrial fibrillation, seizures and pulmonary oedema.
      Approximately 20% of patients to whom an RRT has responded have more than one RRT
      call, and up to one-third have issues around end-of-life care. Calls are least
      common overnight. Between 10 to 25% of patients are admitted to a critical care
      area after the call. The in-hospital mortality for RRT patients is approximately
      25% overall but only 15% in patients without a limitation of medical therapy. RRT
      syndromes can be conceptually described by the trigger for the call (e.g.
      hypotension) or the clinical condition causing the call (e.g. sepsis).
      Alternatively, the RRT call can be described by the major theme of the call: "end
      of-life care", "requiring critical care" and "stable enough to initially remain
      on the ward". Based on these themes, education strategies and quality improvement
      initiatives may be developed to reduce the incidence of RRT calls, further
      improving patient outcome. 

PMID- 24580388
TI  - Effects of different general anaesthetic techniques on immune responses in
      patients undergoing surgery for tongue cancer.
AB  - The aim of this study was to investigate the effects of different general
      anaesthesia techniques on immune responses in patients undergoing surgery for
      tongue cancer. Sixty American Society of Anesthesiologists physical status 1 or 2
      patients undergoing elective reconstructive surgery for tongue cancer were
      randomised to three groups. Group 1 received propofol induction and maintenance
      (TIVA), group 2 received propofol induction and sevoflurane maintenance (MIXED)
      and group 3 received sevoflurane induction and maintenance (SEVO). All patients
      received an infusion of remifentanil. Blood samples were obtained at eight time
      points: 30 minutes before induction (T0); one hour (T1), three hours (T2) and
      five hours (T3) after induction; at the end of the operation (T4); and 24 hours
      (T5), 48 hours (T6) and 72 hours (T7) after operation. The T lymphocyte subsets
      (including CD3(+) cells, CD3(+)CD4(+) cells and CD3(+)CD8(+)cells) and
      CD4(+)/CD8(+) ratio, natural killer cells and B lymphocytes were analysed by flow
      cytometry. All immunological indicators except CD3(+)CD8(+) cells were
      significantly decreased in all groups at T1~T5 compared to T0 (P <0.05). The
      percentages of CD3(+) cells, CD3(+)CD4(+) cells and natural killer cells, and the
      CD4(+)/CD8(+) ratios were significantly lower in the MIXED groups and SEVO groups
      but not the TIVA group at T6 as compared with T0 (P <0.05). There were minor but
      statistically significant differences in the percentages of CD3(+) cells,
      CD3(+)CD4(+) cells and natural killer cells, and the CD4(+)/CD8(+) ratios between
      the SEVO group and the TIVA group at T2approxT6 (P <0.05). These findings suggest
      that propofol has slightly less effect on cellular immune responses than
      sevoflurane. 

PMID- 24580389
TI  - Limited sampling strategy for estimation of amikacin optimal sampling time in
      critically ill adults.
AB  - Aminoglycosides are a class of antibiotics that are commonly used in the
      treatment of gram-negative pathogens in the critically ill population.
      Unfortunately, dosing of these aminoglycosides in critically ill patients is
      difficult due to their altered pharmacokinetics in the critically ill and narrow
      therapeutic index. In this study, we evaluated whether a limited sampling
      strategy can be used to predict the area under the concentration (AUC) curve of
      amikacin concentrations over a 24-hour period after a single dose of intravenous
      amikacin (25 mg/kg). This open-labelled, non-comparative prospective study
      recruited 20 adult critically ill trauma patients with a diagnosis of hospital
      acquired infection. We assessed the best estimate of plasma amikacin
      concentrations over a 24-hour period by multiple stepwise regression, using nine
      blood samples during this study period as the gold standard. Using a jackknife
      procedure, the AUC of amikacin over a 24-hour period was estimated by choosing a
      combination of the amikacin concentrations measured at different time-points.
      Overall, the mean prediction error of all models was not statistically different
      from zero (P >0.05). Based on bias and imprecision, all models gave good estimate
      of AUC of amikacin over a 24-hour period, but a two-point sampling strategy at
      1.5 and 6 hours post-dose appeared to offer the best compromise between accuracy
      and cost-effectiveness in optimising the dosing of amikacin in critically ill
      patients. 

PMID- 24580390
TI  - The effects of different doses of caudal morphine with levobupivacaine on
      postoperative vomiting and quality of analgesia after circumcision.
AB  - The study aim was to investigate the effect of three different morphine doses
      added to levobupivacaine 0.125% for caudal analgesia after circumcision surgery
      in children, particularly in relation to the frequency of postoperative vomiting
      within the first 24 hours following surgery. Two hundred and forty patients aged
      5 to 12 years undergoing circumcision were included in the study. Following
      induction, caudal 0.125% levobupivacaine 0.5 ml/kg was given after adding 7.5, 10
      or 15 ug/kg morphine. The postoperative incidence of vomiting was 5%, 12.5% and
      17.5% in the groups 7.5, 10 and 15 ug/kg morphine, respectively (P=0.012, 7.5
      versus 15 ug/kg groups). Five percent of the 7.5 ug/kg group and none of the
      patients in the other groups required paracetamol within the first 12 hours, and
      there was a significantly greater need for rescue paracetamol over the 24 hours
      in the 7.5 group versus the 15 ug/kg group (P=0.013). Postoperative analgesic
      durations were long and did not differ between groups (1273+/-338, 1361+/-192 and
      1426+/-48 minutes, respectively, P=0.08). In conclusion, because the incidence of
      vomiting is very low, the duration of postoperative analgesia is long and a dose
      of 7.5 ug/kg caudal morphine is much lower than doses previously reported to be
      associated with respiratory depression, this study supports the use of 7.5 ug/kg
      caudal morphine added to 0.125% levobupivacaine for circumcision surgery. 

PMID- 24580391
TI  - Glycaemic control and long-term outcomes following transition from modified
      intensive insulin therapy to conventional glycaemic control.
AB  - This retrospective observational cohort study compared glycaemic control and long
      term outcomes following transition from a modified intensive insulin therapy
      (mIIT) regimen to conventional glycaemic control (CGC) in adult patients admitted
      to a tertiary adult general intensive care unit, during two 24-month periods,
      before and after the publication of the Normoglycemia in Intensive Care
      Evaluation and Surviving Using Glucose Algorithm Regulation (NICE-SUGAR) trial.
      The before NICE-SUGAR cohort received mIIT (target glycaemic ranges 4.4 to 7.0
      mmol/l), while the after NICE-SUGAR cohort received CGC (target glycaemic range
      7.1 to 9.0 mmol/l). A total of 5202 patients were included in the study. With
      transition from mIIT to CGC, the mean time-weighted glucose increased from 6.94
      mmol/l to 8.2 mmol/l (P <0.0001). A similar increase was observed in other
      glycaemic indices (mean, highest and lowest glucose values, P <0.0001 for all).
      The adjusted 90-day odds ratio for mortality decreased by 47% with transition
      from mIIT to CGC (odds ratio 1.47 (95% confidence interval, 1.22 to 1.78) (P
      <0.0001). The rate of severe and moderate hypoglycaemia also decreased from 1.2
      to 0.4% (P=0.004) and from 23.3 to 5.9% (P <0.0001), respectively. mIIT was
      associated with an increased risk of moderate and severe hypoglycaemia compared
      to CGC (odds ratio 3.1 (1.51 to 6.39) (P=0.002), 6.29 (5.1 to 7.75) (P <0.0001)).
      Changes in recommended glycaemic control were translated into practice, with
      increased glycaemic indices and decreased rates of severe and moderate
      hypoglycaemia after the introduction of CGC. The associated decrease in 90-day
      mortality suggests mIIT was not superior to CGC, despite a lower hypoglycaemia
      rate than in previous IIT trials. Our findings support the continued use of CGC. 

PMID- 24580392
TI  - Management of severe hypercapnia post cardiac arrest with extracorporeal carbon
      dioxide removal.
AB  - Normocapnia is recommended in intensive care management of patients after out-of
      hospital cardiac arrest. While normocapnia is usually achievable, it may be
      therapeutically challenging, particularly in patients with airflow obstruction.
      Conventional mechanical ventilation may not be adequate to provide optimal
      ventilation in such patients. One of the recent advances in critical care
      management of hypercapnia is the advent of newer, low-flow extracorporeal carbon
      dioxide clearance devices. These are simpler and less invasive than conventional
      extracorporeal devices. We report the first case of using a novel, extracorporeal
      carbon dioxide removal device in Australia on a patient with out-of-hospital
      cardiac arrest where mechanical ventilation failed to achieve normocapnia. 

PMID- 24580393
TI  - Copper removal strategies for Wilson's disease crisis in the ICU.
AB  - Wilson's disease is a rare, inherited, autosomal recessive disorder of copper
      metabolism which leads to an accumulation of copper in body tissues. If a patient
      develops a Wilson's crisis, mortality can approach 100%. The treatment of such
      patients is mostly organ support but a possible treatment goal is to try to
      rapidly remove copper from their system. We performed a literature search on
      methods for de-coppering strategies for patients in intensive care with known
      Wilson's disease. We found 11 case reports where therapeutic plasma exchange was
      used and six case reports where various forms of albumin dialysis were used as
      techniques for rapidly reducing serum copper levels. To date, the case reports
      are encouraging that therapeutic plasma exchange and albumin dialysis can either
      delay or prevent the need for liver transplantation in patients with fulminant
      hepatic failure due to Wilson's disease. However, these case reports are mainly
      in the paediatric or young adult population, thus further studies in adults are
      warranted. 

PMID- 24580394
TI  - Intravenous infusion of sterile water for the treatment of hypernatraemia.
AB  - Little research has been carried out into the infusion of intravenous sterile
      water for the treatment of hypernatraemia, and it remains a contentious issue. We
      conducted a review of the literature and extract results following an extensive
      search of Medline 1946, Embase 1974, ProQuest, evidence-based practice resources,
      national and international guideline sites and the publications of various
      professional bodies. The review is presented on the infusion of sterile water
      (hypotonic fluid) to lower serum sodium level in those circumstances when enteral
      supplementation of water is not possible, such as in postoperative patients or
      when other isotonic fluids (such as 5% dextrose in water infusion) are less than
      ideal-for example, hyperglycaemic patients on an insulin infusion. Absence of
      guidelines has limited the use of sterile water, even as an off-label drug when
      it can be administered relatively safely via a central line. 

PMID- 24580395
TI  - Yet another missed central venous guidewire!

PMID- 24580396
TI  - Air-raising ST-uff.

PMID- 24580397
TI  - In reply to Gomez Rios.

PMID- 24580398
TI  - The role of innominate artery ligation in the management of massive haemorrhage
      from trachea-innominate artery fistula.

PMID- 24580399
TI  - Circumcision without anaesthesia.

PMID- 24580400
TI  - Propofol-associated urine discolouration in critically ill patients-case reports.

PMID- 24580401
TI  - Sedation for voiding cystourethrograms with intranasal dexmedetomidine.

PMID- 24580402
TI  - Inadvertent high central neuraxial block and possible total spinal anaesthesia
      occurring after nerve stimulation guided thoracic paravertebral block.

PMID- 24580403
TI  - Emergent endotracheal tube exchange following acute obstruction of an
      electromyography monitoring endotracheal tube.

PMID- 24580404
TI  - Apical hypertrophic cardiomyopathy in a parturient-electrocardiogram led the way.

PMID- 24580405
TI  - Desflurane is a potent anaesthetic atmospheric pollutant and should be removed
      from our clinical practice.

PMID- 24580406
TI  - Tracheal tube compression in an obese patient.

PMID- 24580407
TI  - Not all bag-valva-mask devices are created equal: beware a possible lower FiO2
      during spontaneous vetilation.

PMID- 24580408
TI  - Successful pulmonary artery catheter flotation in a patient with a persistent
      left superior vena cava.

PMID- 24580409
TI  - Effectiveness of targeted therapy as monotherapy or combined therapy in patients
      with relapsed or refractory multiple myeloma: a systematic review and meta
      analysis.
AB  - OBJECTIVES: The aim of this systematic review was to evaluate the efficacy and
      safety of targeted agents used as monotherapy or combined therapy in patients
      with relapsed/refractory multiple myeloma (MM). METHODS: The systematic
      literature search was conducted in PubMed, Embase, Cochrane Library till 27 May
      2013. RESULTS: Four randomized controlled trials were included. The meta-analysis
      showed that combined therapy significantly improved progression-free survival
      compared with monotherapy (P < 0.05). However, there was not a significant
      difference between monotherapy and combined therapy in overall survival (P >
      0.05). The combined therapy also significantly increased the risk of serious
      adverse events and grade 3/4 AEs compared to monotherapy (P < 0.05). Overall, the
      results of comparisons between monotherapy and combined therapy in individual
      trials were differentiated, and some combinations were not more effective than
      monotherapy (bortezomib plub bevacizumab vs. bortezomib and thalidomide plus
      INFalpha vs. thalidomide) which emphasizes the role of individualized therapy in
      relapsed/refractory MM especially in the elderly or patients with significant
      comorbidities. CONCLUSIONS: The results of this meta-analysis showed that
      combined therapy is superior to monotherapy only in some end points and it is
      less tolerated in patients with relapsed/refractory MM. Thus, the overall
      superiority of complex therapy to monotherapy depends on the combination of the
      targeted agents.

PMID- 24580410
TI  - Higher thrombin activatable fibrinolysis inhibitor levels are associated with
      inflammation in attack-free familial Mediterranean fever patients.
AB  - BACKGROUND: Coagulation abnormalities have been reported in familial
      Mediterranean fever (FMF) patients with amyloidosis and nephrotic syndrome; but
      there is not enough data about the continuity of the thrombogenic activity in FMF
      patients in clinical remission. The purpose of this study was to assess thrombin
      activatable fibrinolysis inhibitor (TAFI) levels and its relationship with
      fibrinolytic activity and also evaluate relationships between mutations and
      clinical signs in attack-free patients without amyloidosis. METHODS: Seventy-nine
      FMF patients and 40 healthy adults were included. The study group was divided
      into five groups as follows: first group, homozygote M694V; second group,
      homozygote M680I; third group, M694V in one allele, the other allele have other
      mutations or not; fourth group, other mutations; and fifth group, no mutation.
      RESULTS: Serum TAFI levels were significantly increased in patients compared with
      healthy individuals (116.64 +/- 21.8 vs. 78.48 +/- 19.7 MUg/mL, p < 0.001) and a
      positive correlation was detected between TAFI antigen level and erythrocyte
      sedimentation rate and C-reactive protein levels (r = 0.247, p = 0.029 and r =
      0.252, p = 0.032, respectively). Mean fibrinogen and TAFI levels were
      significantly higher in Group 1 than the other groups (p = 0.04 and p = 0.001,
      respectively) and in Group 3 it was higher than Groups 2, 4 and 5 (p = 0.04 and p
      = 0.001, respectively). CONCLUSIONS: High level of TAFI antigen in attack-free
      period of FMF disease shows ongoing subclinical inflammation and
      hypercoagulability. Clinicians should be careful about thrombosis even in
      patients at clinical remission. Also, genetic tests must be considered to predict
      clinical outcome and to reduce complications of FMF disease.

PMID- 24580411
TI  - Sharp lines due to Cr3+ and Mn2+ impurities in insulators: going beyond the usual
      Tanabe-Sugano approach.
AB  - This work is aimed at understanding the different behavior of optical sharp lines
      (corresponding to 10Dq-independent transitions) of Mn(2+) and Cr(3+) in normal
      and inverted perovskites that cannot be explained within the usual Tanabe-Sugano
      approach. In particular, we want to clarify why on passing from KMgF3:M to
      LiBaF3:M (M = Mn(2+), Cr(3+)) the energy, E((6)A1 -> (4)A1), for Mn(2+) decreases
      by Delta = 1100 cm(-1), while Delta < 100 cm(-1) for the energy E((2)E ->( 4)A2)
      corresponding to Cr(3+). The origin of this surprising difference in these model
      systems is clarified by writing the transition energies of MF6 complexes through
      the ten Coulomb and exchange integrals consistent with the cubic symmetry and not
      considered in the usual Tanabe-Sugano approach. It is shown that E((6)A1 ->
      (4)A1) depends on exchange integrals K(3z(2) - r(2), xy) and K(x(2) - y(2), xy),
      while E((2)E -> (4)A2) depends on K(xz, yz) where the two involved electrons
      display a pi character. These exchange integrals have been calculated just
      considering a MF6 unit subject to the internal electric field due to the rest of
      the lattice ions. In addition to a reasonably reproduction of the main trends
      observed experimentally for the model systems, the present calculations prove
      that the exchange integrals are not related in a simple way to the covalency of
      involved orbitals. Particular attention is also paid to explain why the
      transitions, which are 10Dq-independent are less sensitive to the host lattice
      change than those which do depend on 10Dq. The present work shows that K(xz, yz)
      for Cr(3+) is particularly insensitive to the host lattice change and thus sheds
      light on the origin of the near independence of E((2)E -> (4)A2) along the series
      of oxides doped with such an impurity . 

PMID- 24580412
TI  - Recurrent mitral stenosis and an intra-atrial mitral valve mass 40 years after
      tubbs mitral commissurotomy.

PMID- 24580415
TI  - Distortion/Interaction analysis reveals the origins of selectivities in iridium
      catalyzed C-H borylation of substituted arenes and 5-membered heterocycles.
AB  - The iridium-catalyzed borylation of mono- and disubstituted arenes and
      heteroarenes has been studied with density functional theory. The
      distortion/interaction model was employed to understand the origins of
      selectivities in these reactions. Computations revealed that the transition
      states for C-H oxidative addition are very late, resembling the aryl iridium
      hydride intermediate with a fully formed Ir-C bond. Consequently, the
      regioselectivity is mainly controlled by differences in the interaction energies
      between the iridium catalyst and arene carbon. 

PMID- 24580413
TI  - The Friend leukaemia virus integration 1 (Fli-1) transcription factor affects
      lupus nephritis development by regulating inflammatory cell infiltration into the
      kidney.
AB  - The transcription factor Friend leukaemia virus integration 1 (Fli-1) is
      implicated in the pathogenesis of systemic lupus erythematosus in both human
      patients and murine models of lupus. Murphy Roths large (MRL)/lpr mice and New
      Zealand mixed (NZM)2410 mice, murine models of lupus, with decreased expression
      of Fli-1 had significantly prolonged survival and reduced nephritis. Lupus
      nephritis is a major cause of mortality and morbidity in patients, and
      inflammatory cell infiltration plays a key role in the development of the
      disease. To study how the expression of Fli-1 affects the infiltration of
      inflammatory cells into the kidneys, we generated congenic enhanced green
      fluorescent protein (GFP) transgenic MRL/lpr mice. A significantly increased
      number of GFP-expressing inflammatory cells infiltrated the kidneys of wild-type
      MRL/lpr mice compared to Fli-1 heterozygous (Fli-1(+/-)) MRL/lpr mice after
      injection of GFP(+) cells. Expression of inflammatory chemokine mRNA, including
      chemokine (C-C motif) ligand (CCL)2, CCL3, CCL4 and CCL5, was significantly lower
      in the kidneys from Fli-1(+/-) MRL/lpr mice compared to wild-type littermates.
      Numbers of infiltrated cells into the kidneys correlate with expression levels of
      CCL2, CCL4 and CCL5, but not the titres of anti-dsDNA autoantibodies in these
      mice. Significantly increased inflammatory cells from wild-type MRL/lpr mice
      infiltrated into kidneys compared to the cells from Fli-1(+/-) MRL/lpr mice. The
      chemotaxis of inflammatory cells from Fli-1(+/-) MRL/lpr mice towards each
      chemokine was decreased significantly compared to inflammatory cells from wild
      type MRL/lpr mice in the transwell migration assay in vitro. Our results indicate
      that Fli-1 affects lupus nephritis development by regulating the expression of
      chemokines in the kidney and the migration of inflammatory cells.

PMID- 24580414
TI  - Overgeneral autobiographical memory in children of depressed mothers.
AB  - The goal of this study was to examine overgeneral autobiographical memory in a
      population at-risk for depression (i.e., children of depressed mothers). We
      predicted that children of depressed mothers would display less-specific memories
      than children of non-depressed mothers and that these results would be observed
      among children with no prior history of depression themselves. Participants in
      this study were children (age 8-14; 50% girls, 83% Caucasian) of mothers with (n
      = 103) or without (n = 120) a history of major depressive disorder during the
      child's life. Mothers' and children's diagnoses were confirmed with a diagnostic
      interview, and children completed the Autobiographical Memory Test and a measure
      of depressive symptoms. We found that children of depressed mothers, compared to
      children of non-depressed mothers, recalled less-specific memories in response to
      negative cue words but not positive cue words. Importantly, these results were
      maintained even when we statistically controlled for the influence of children's
      current depressive symptom levels and excluded children with currently depressed
      mothers. These results suggest that overgeneral autobiographical memory for
      negative events may serve as a marker of depression risk among high-risk children
      with no prior depression history. 

PMID- 24580416
TI  - Stance phase kinematics and kinetics of horses trotting over poles.
AB  - REASON FOR PERFORMING STUDY: Trotting over poles is frequently used
      therapeutically to restore swing phase ranges of joint motion. It is not known
      whether ground reaction forces (GRFs) increase as the swing phase limbs are
      lifted higher to clear the poles. Higher GRFs might be painful or jeopardise
      healing of musculoskeletal injuries. OBJECTIVES: To measure stance phase
      kinematics and GRFs in the forelimbs and hindlimbs of horses trotting on level
      ground, over low poles and over high poles, and to test the hypothesis that
      trotting over poles is associated with increases in peak GRFs and impulses in the
      supporting hindlimb and forelimb compared with trotting over level ground. STUDY
      DESIGN: Repeated measures experimental study on horses with normal gait. METHODS:
      Kinematic and GRF data were collected from 8 horses trotting on level ground
      under 3 conditions performed in random order: no poles, low (11 cm) poles and
      high (20 cm) poles spaced 1.05 +/- 0.05 m apart. Spatiotemporal and angular
      kinematic variables and GRFs were measured during stance. Comparisons among
      conditions were made using repeated measures ANOVA (P<0.05) with Bonferroni
      correction for post hoc testing. RESULTS: The only GRF component that increased
      when trotting over poles was peak forelimb braking GRF. Forelimb vertical and
      braking impulses increased and the transverse impulse changed from medially to
      laterally directed. Extension of the metatarsophalangeal and metacarpophalangeal
      joints did not change. CONCLUSIONS: The fact that peak vertical forces and
      extension of the metatarsophalangeal and metacarpophalangeal joints did not
      increase when trotting over poles suggests that loading of the musculoskeletal
      tissues is comparable with that associated with trotting on level ground in
      horses with symmetrical movement at trot. The findings support the use of trot
      poles during rehabilitation from lameness in horses that move symmetrically. The
      generation of laterally directed forelimb transverse forces suggests that
      trotting over poles may recruit the forelimb adductor musculature.

PMID- 24580417
TI  - A versatile dinucleating ligand containing sulfonamide groups.
AB  - Copper, iron, and gallium coordination chemistries of the new pentadentate bis
      sulfonamide ligand 2,6-bis(N-2-pyridylmethylsulfonamido)-4-methylphenol (psmpH3)
      were investigated. PsmpH3 is capable of varying degrees of deprotonation, and
      notably, complexes containing the fully trideprotonated ligand can be prepared in
      aqueous solutions using only divalent metal ions. Two of the copper(II)
      complexes, [Cu2(psmp)(OH)] and [Cu2(psmp)(OAc)2](-), demonstrate the anticipated
      1:2 ligand/metal stoichiometry and show that the dimetallic binding site created
      for exogenous ligands possesses high inherent flexibility since additional one-
      and three-atom bridging ligands bridge the two copper(II) ions in each complex,
      respectively. This gives rise to a difference of 0.4 A in the Cu...Cu distances.
      Complexes with 2:3 and 2:1 ligand/metal stoichiometries for the divalent and
      trivalent metal ions, respectively, were observed in [Cu3(psmp)2(H2O)] and
      [M(psmpH)(psmpH2)], where M = Ga(III), Fe(III). The deprotonated tridentate N-2
      pyridylsulfonylmethylphenolato moieties chelate the metal ions in a meridional
      fashion, whereas in [Cu3(psmp)2(H2O)] the rare MU2-N-sulfonamido bridging
      coordination mode is observed. In the bis-ligand mononuclear complexes, one
      picolyl arm of each ligand is protonated and uncoordinated. Magnetic
      susceptibility measurements on the doubly and triply bridged dicopper(II)
      complexes indicate strong and medium strength antiferromagnetic coupling
      interactions, with J = 234 cm(-1) and 115 cm(-1) for [Cu2(psmp)(OH)] and
      [Cu2(psmp)(OAc)2](-), respectively (in HHDvV =...+JS1S2 convention). The
      trinuclear [Cu3(psmp)2(H2O)], in which the central copper ion is linked to two
      flanking copper atoms by two MU2-N-sulfonamido bridges and two phenoxide bridges
      shows an overall magnetic behavior of antiferromagnetic coupling. This is
      corroborated computationally by broken-symmetry density functional theory, which
      for isotropic modeling of the coupling predicts an antiferromagnetic coupling
      strength of J = 70.5 cm(-1). 

PMID- 24580418
TI  - Dose-controlled, floating evaporative self-assembly and alignment of
      semiconducting carbon nanotubes from organic solvents.
AB  - Arrays of aligned semiconducting single-walled carbon nanotubes (s-SWCNTs) with
      exceptional electronic-type purity were deposited at high deposition velocity of
      5 mm min(-1) by a novel "dose-controlled, floating evaporative self-assembly"
      process with excellent control over the placement of stripes and quantity of s
      SWCNTs deposited. This approach uses the diffusion of organic solvent on the
      water-air interface to deposit aligned s-SWCNT (99.9%) tubes on a partially
      submerged hydrophobic substrate, which is withdrawn vertically from the surface
      of water. By decoupling the s-SWCNT stripe formation from the evaporation of the
      bulk solution and by iteratively applying the s-SWCNTs in controlled "doses", we
      show through polarized Raman studies that the s-SWCNTs are aligned within +/-14
      degrees , are packed at a density of ~50 s-SWCNTs MUm(-1), and constitute
      primarily a well-ordered monodispersed layer. The resulting field-effect
      transistor devices show high performance with a mobility of 38 cm(2) V(-1) s(-1)
      and on/off ratio of 2.2 * 10(6) at 9 MUm channel length. 

PMID- 24580419
TI  - Graph-theoretic approach to quantum correlations.
AB  - Correlations in Bell and noncontextuality inequalities can be expressed as a
      positive linear combination of probabilities of events. Exclusive events can be
      represented as adjacent vertices of a graph, so correlations can be associated to
      a subgraph. We show that the maximum value of the correlations for classical,
      quantum, and more general theories is the independence number, the Lovasz number,
      and the fractional packing number of this subgraph, respectively. We also show
      that, for any graph, there is always a correlation experiment such that the set
      of quantum probabilities is exactly the Grotschel-Lovasz-Schrijver theta body.
      This identifies these combinatorial notions as fundamental physical objects and
      provides a method for singling out experiments with quantum correlations on
      demand. 

PMID- 24580420
TI  - Many-body matter-wave dark soliton.
AB  - The Gross-Pitaevskii equation--which describes interacting bosons in the mean
      field approximation--possesses solitonic solutions in dimension one. For
      repulsively interacting particles, the stationary soliton is dark, i.e., is
      represented by a local density minimum. Many-body effects may lead to filling of
      the dark soliton. Using quasiexact many-body simulations, we show that, in single
      realizations, the soliton appears totally dark although the single particle
      density tends to be uniform.

PMID- 24580421
TI  - Quantum Joule-Thomson effect in a saturated homogeneous Bose gas.
AB  - We study the thermodynamics of Bose-Einstein condensation in a weakly interacting
      quasihomogeneous atomic gas, prepared in an optical-box trap. We characterize the
      critical point for condensation and observe saturation of the thermal component
      in a partially condensed cloud, in agreement with Einstein's textbook picture of
      a purely statistical phase transition. Finally, we observe the quantum Joule
      Thomson effect, namely isoenthalpic cooling of an (essentially) ideal gas. In our
      experiments this cooling occurs spontaneously, due to energy-independent
      collisions with the background gas in the vacuum chamber. We extract a Joule
      Thomson coefficient MUJT>10(9)  K/bar, about 10 orders of magnitude larger than
      observed in classical gases.

PMID- 24580422
TI  - Necessary and sufficient condition for state-independent contextual measurement
      scenarios.
AB  - The problem of identifying measurement scenarios capable of revealing state
      independent contextuality in a given Hilbert space dimension is considered. We
      begin by showing that for any given dimension d and any measurement scenario
      consisting of projective measurements, (i) the measure of contextuality of a
      quantum state is entirely determined by its spectrum, so that pure and maximally
      mixed states represent the two extremes of contextual behavior, and that (ii)
      state-independent contextuality is equivalent to the contextuality of the
      maximally mixed state up to a global unitary transformation. We then derive a
      necessary and sufficient condition for a measurement scenario represented by an
      orthogonality graph to reveal state-independent contextuality. This condition is
      given in terms of the fractional chromatic number of the graph chif(G) and is
      shown to identify all state-independent contextual measurement scenarios
      including those that go beyond the original Kochen-Specker paradigm. 

PMID- 24580423
TI  - Observation of conformal symmetry breaking and scale invariance in expanding
      Fermi gases.
AB  - We precisely test scale invariance and examine local thermal equilibrium in the
      hydrodynamic expansion of a Fermi gas of atoms as a function of interaction
      strength. After release from an anisotropic optical trap, we observe that a
      resonantly interacting gas obeys scale-invariant hydrodynamics, where the mean
      square cloud size <r2>=<x2+y2+z2> expands ballistically (like a noninteracting
      gas) and the energy-averaged bulk viscosity is consistent with zero,
      0.00(0.04)hn, with n the density. In contrast, the aspect ratios of the cloud
      exhibit anisotropic "elliptic" flow with an energy-dependent shear viscosity.
      Tuning away from resonance, we observe conformal symmetry breaking, where <r2>
      deviates from ballistic flow.

PMID- 24580424
TI  - Weak value amplification is suboptimal for estimation and detection.
AB  - We show by using statistically rigorous arguments that the technique of weak
      value amplification does not perform better than standard statistical techniques
      for the tasks of single parameter estimation and signal detection. Specifically,
      we prove that postselection, a necessary ingredient for weak value amplification,
      decreases estimation accuracy and, moreover, arranging for anomalously large weak
      values is a suboptimal strategy. In doing so, we explicitly provide the optimal
      estimator, which in turn allows us to identify the optimal experimental
      arrangement to be the one in which all outcomes have equal weak values (all as
      small as possible) and the initial state of the meter is the maximal eigenvalue
      of the square of the system observable. Finally, we give precise quantitative
      conditions for when weak measurement (measurements without postselection or
      anomalously large weak values) can mitigate the effect of uncharacterized
      technical noise in estimation. 

PMID- 24580425
TI  - All-optical quantum information processing using Rydberg gates.
AB  - In this Letter, we propose a hybrid scheme to implement a photonic controlled-z
      (CZ) gate using photon storage in highly excited Rydberg states, which controls
      the effective photon-photon interaction using resonant microwave fields. Our
      scheme decouples the light propagation from the interaction and exploits the
      spatial properties of the dipole blockade phenomenon to realize a CZ gate with
      minimal loss and mode distortion. By excluding the coupling efficiency,
      fidelities exceeding 95% are achievable and are found to be mainly limited by
      motional dephasing and the finite lifetime of the Rydberg levels. 

PMID- 24580427
TI  - Proposal for verification of the haldane phase using trapped ions.
AB  - A proposal to use trapped ions to implement spin-one XXZ antiferromagnetic chains
      as an experimental tool to explore the Haldane phase is presented. We explain how
      to reach the Haldane phase adiabatically, demonstrate the robustness of the
      ground states to noise in the magnetic field and Rabi frequencies, and propose a
      way to detect them using their characteristics: an excitation gap and
      exponentially decaying correlations, a nonvanishing nonlocal string order, and a
      double degenerate entanglement spectrum. Scaling up to higher dimensions and more
      frustrated lattices, we obtain richer phase diagrams, and we can reach spin
      liquid phase, which can be detected by its entanglement entropy which obeys the
      boundary law. 

PMID- 24580426
TI  - Quantum digital signatures without quantum memory.
AB  - Quantum digital signatures (QDSs) allow the sending of messages from one sender
      to multiple recipients, with the guarantee that messages cannot be forged or
      tampered with. Additionally, messages cannot be repudiated--if one recipient
      accepts a message, she is guaranteed that others will accept the same message as
      well. While messaging with these types of security guarantees are routinely
      performed in the modern digital world, current technologies only offer security
      under computational assumptions. QDSs, on the other hand, offer security
      guaranteed by quantum mechanics. All thus far proposed variants of QDSs require
      long-term, high quality quantum memory, making them unfeasible in the foreseeable
      future. Here, we present a QDS scheme where no quantum memory is required, which
      also needs just linear optics. This makes QDSs feasible with current technology.

PMID- 24580428
TI  - Quantum storage of heralded single photons in a praseodymium-doped crystal.
AB  - We report on experiments demonstrating the reversible mapping of heralded single
      photons to long-lived collective optical atomic excitations stored in a
      Pr3+:Y2SiO5 crystal. A cavity-enhanced spontaneous down-conversion source is
      employed to produce widely nondegenerate narrow-band (~2  MHz) photon pairs. The
      idler photons, whose frequency is compatible with telecommunication optical
      fibers, are used to herald the creation of the signal photons, compatible with
      the Pr3+ transition. The signal photons are stored and retrieved using the atomic
      frequency comb protocol. We demonstrate storage times up to 4.5  MUs while
      preserving nonclassical correlations between the heralding and the retrieved
      photon. This is more than 20 times longer than in previous realizations in solid
      state devices, and implemented in a system ideally suited for the extension to
      spin-wave storage. 

PMID- 24580429
TI  - Anomalous heat diffusion.
AB  - Consider anomalous energy spread in solid phases, i.e., <Deltax(2)(t)>E=?(x
      <x>E)(2)rhoE(x,t)dx?t(beta), as induced by a small initial excess energy
      perturbation distribution rhoE(x,t=0) away from equilibrium. The second
      derivative of this variance of the nonequilibrium excess energy distribution is
      shown to rigorously obey the intriguing relation
      d(2)<Deltax(2)(t)>E/dt2=2CJJ(t)/(kBT(2)c), where CJJ(t) equals the thermal
      equilibrium total heat flux autocorrelation function and c is the specific
      volumetric heat capacity. Its integral assumes a time-local Helfand-like
      relation. Given that the averaged nonequilibrium heat flux is governed by an
      anomalous heat conductivity, the energy diffusion scaling determines a
      corresponding anomalous thermal conductivity scaling behavior.

PMID- 24580430
TI  - Exact large-deviation statistics for a nonequilibrium quantum spin chain.
AB  - We consider a one-dimensional XX spin chain in a nonequilibrium setting with a
      Lindblad-type boundary driving. By calculating large-deviation rate function in
      the thermodynamic limit, a generalization of free energy to a nonequilibrium
      setting, we obtain a complete distribution of current, including closed
      expressions for lower-order cumulants. We also identify two phase-transition-like
      behaviors in either the thermodynamic limit, at which the current probability
      distribution becomes discontinuous, or at maximal driving, when the range of
      possible current values changes discontinuously. In the thermodynamic limit the
      current has a finite upper and lower bound. We also explicitly confirm
      nonequilibrium fluctuation relation and show that the current distribution is the
      same under mapping of the coupling strength Gamma->1/Gamma. 

PMID- 24580431
TI  - Inequality between size and angular momentum for bodies.
AB  - A universal inequality that bounds the angular momentum of a body by the square
      of its size is presented and heuristic physical arguments are given to support
      it. We prove a version of this inequality, as consequence of the Einstein
      equations, for the case of rotating axially symmetric, constant density, bodies.
      Finally, the physical relevance of this result is discussed. 

PMID- 24580432
TI  - Violations of the equivalence principle by a nonlocally reconstructed vacuum at
      the black hole horizon.
AB  - If information escapes from an evaporating black hole, then field modes just
      outside the horizon must be thermally entangled with distant Hawking radiation.
      But for an infalling observer to find empty space at the horizon, the same modes
      would have to be entangled with the black hole interior. Thus, unitarity appears
      to require a "firewall" at the horizon. Identifying the interior with the distant
      radiation promises to resolve the entanglement conflict and restore the vacuum.
      But the map must adjust for any interactions, or else the firewall will reappear
      if the Hawking radiation scatters off the cosmic microwave background. Such a map
      produces a "frozen vacuum," a phenomenon that is arguably worse than a firewall.
      An infalling observer is unable to excite the vacuum near the horizon. This
      allows the horizon to be locally detected and so violates the equivalence
      principle. 

PMID- 24580433
TI  - Gravitational waves from the sound of a first order phase transition.
AB  - We report on the first three-dimensional numerical simulations of first-order
      phase transitions in the early Universe to include the cosmic fluid as well as
      the scalar field order parameter. We calculate the gravitational wave (GW)
      spectrum resulting from the nucleation, expansion, and collision of bubbles of
      the low-temperature phase, for phase transition strengths and bubble wall
      velocities covering many cases of interest. We find that the compression waves in
      the fluid continue to be a source of GWs long after the bubbles have merged, a
      new effect not taken properly into account in previous modeling of the GW source.
      For a wide range of models, the main source of the GWs produced by a phase
      transition is, therefore, the sound the bubbles make. 

PMID- 24580435
TI  - Rotation of the cosmic microwave background polarization from weak gravitational
      lensing.
AB  - When a cosmic microwave background (CMB) photon travels from the surface of last
      scatter through spacetime metric perturbations, the polarization vector may
      rotate about its direction of propagation. This gravitational rotation is
      distinct from, and occurs in addition to, the lensing deflection of the photon
      trajectory. This rotation can be sourced by linear vector or tensor metric
      perturbations and is fully coherent with the curl deflection field. Therefore,
      lensing corrections to the CMB polarization power spectra as well as the
      temperature-polarization cross correlations due to nonscalar perturbations are
      modified. The rotation does not affect lensing by linear scalar perturbations,
      but needs to be included when calculations go to higher orders. We present
      complete results for weak lensing of the full-sky CMB power spectra by general
      linear metric perturbations, taking into account both deflection of the photon
      trajectory and rotation of the polarization. For the case of lensing by
      gravitational waves, we show that the B modes induced by the rotation largely
      cancel those induced by the curl component of deflection. 

PMID- 24580436
TI  - Cosmology with void-galaxy correlations.
AB  - Galaxy bias, the unknown relationship between the clustering of galaxies and the
      underlying dark matter density field is a major hurdle for cosmological inference
      from large-scale structure. While traditional analyses focus on the absolute
      clustering amplitude of high-density regions mapped out by galaxy surveys, we
      propose a relative measurement that compares those to the underdense regions,
      cosmic voids. On the basis of realistic mock catalogs we demonstrate that cross
      correlating galaxies and voids opens up the possibility to calibrate galaxy bias
      and to define a static ruler thanks to the observable geometric nature of voids.
      We illustrate how the clustering of voids is related to mass compensation and
      show that volume-exclusion significantly reduces the degree of stochasticity in
      their spatial distribution. Extracting the spherically averaged distribution of
      galaxies inside voids from their cross correlations reveals a remarkable
      concordance with the mass-density profile of voids. 

PMID- 24580434
TI  - Search for low-mass weakly interacting massive particles using voltage-assisted
      calorimetric ionization detection in the SuperCDMS experiment.
AB  - SuperCDMS is an experiment designed to directly detect weakly interacting massive
      particles (WIMPs), a favored candidate for dark matter ubiquitous in the
      Universe. In this Letter, we present WIMP-search results using a calorimetric
      technique we call CDMSlite, which relies on voltage-assisted Luke-Neganov
      amplification of the ionization energy deposited by particle interactions. The
      data were collected with a single 0.6 kg germanium detector running for ten live
      days at the Soudan Underground Laboratory. A low energy threshold of 170  eVee
      (electron equivalent) was obtained, which allows us to constrain new WIMP-nucleon
      spin-independent parameter space for WIMP masses below 6  GeV/c2. 

PMID- 24580437
TI  - Nuclear shadowing in the holographic framework.
AB  - The nucleon structure function F2(N) computed in a holographic framework can be
      used to describe nuclear deep inelastic scattering effects provided that a
      rescaling of the Q2 momentum and of the IR hard-wall parameter z0 is made. The
      ratios RA=F2(A)/F2(N) can be obtained in terms of a single rescaling parameter
      lambdaA for each nucleus. The resulting ratios agree with the experiment in a
      wide range of the shadowing region.

PMID- 24580442
TI  - Heavy flavor puzzle at LHC: a serendipitous interplay of jet suppression and
      fragmentation.
AB  - Both charged hadrons and D mesons are considered to be excellent probes of QCD
      matter created in ultrarelativistic heavy ion collisions. Surprisingly, recent
      experimental observations at LHC show the same jet suppression for these two
      probes, which--contrary to pQCD expectations--may suggest similar energy losses
      for light quarks and gluons in the QCD medium. We here use our recently developed
      energy loss formalism in a finite-size dynamical QCD medium to analyze this
      phenomenon that we denote as the "heavy flavor puzzle at LHC." We show that this
      puzzle is a consequence of an unusual combination of the suppression and
      fragmentation patterns and, in fact, does not require invoking the same energy
      loss for light partons. Furthermore, we show that this combination leads to a
      simple relationship between the suppressions of charged hadrons and D mesons and
      the corresponding bare quark suppressions. Consequently, a coincidental matching
      of jet suppression and fragmentation allows considerably simplifying the
      interpretation of the corresponding experimental data.

PMID- 24580443
TI  - Isospin breaking in the nucleon mass and the sensitivity of beta decays to new
      physics.
AB  - We discuss the consequences of the approximate conservation of the vector and
      axial currents for the hadronic matrix elements appearing in beta decay if
      nonstandard interactions are present. In particular, the isovector (pseudo)scalar
      charge gS(P) of the nucleon can be related to the difference (sum) of the nucleon
      masses in the absence of electromagnetic effects. Using recent determinations of
      these quantities from phenomenological and lattice QCD studies we obtain the
      accurate values gS=1.02(11) and gP=349(9) in the modified minimal subtraction
      scheme at MU=2  GeV. The consequences for searches of nonstandard scalar
      interactions in nuclear beta decays are studied, finding for the corresponding
      Wilson coefficient epsilonS=0.0012(24) at 90% C.L., which is significantly more
      stringent than current LHC bounds and previous low-energy bounds using less
      precise gS values. We argue that our results could be rapidly improved with
      updated computations and the direct calculation of certain ratios in lattice QCD.
      Finally, we discuss the pion-pole enhancement of gP, which makes beta decays much
      more sensitive to nonstandard pseudoscalar interactions than previously thought. 

PMID- 24580441
TI  - Paramagnetic squeezing of QCD matter.
AB  - We determine the magnetization of quantum chromodynamics for several temperatures
      around and above the transition between the hadronic and the quark-gluon phases
      of strongly interacting matter. We obtain a paramagnetic response that increases
      in strength with the temperature. We argue that due to this paramagnetism, chunks
      of quark-gluon plasma produced in noncentral heavy ion collisions should become
      squeezed perpendicular to the magnetic field. This anisotropy will then
      contribute to the elliptic flow v2 observed in such collisions, in addition to
      the pressure gradient that is usually taken into account. We present a simple
      estimate for the magnitude of this new effect and a rough comparison to the
      effect due to the initial collision geometry. We conclude that the paramagnetic
      effect might have a significant impact on the value of v2. 

PMID- 24580445
TI  - Synthetic gauge fields in synthetic dimensions.
AB  - We describe a simple technique for generating a cold-atom lattice pierced by a
      uniform magnetic field. Our method is to extend a one-dimensional optical lattice
      into the "dimension" provided by the internal atomic degrees of freedom, yielding
      a synthetic two-dimensional lattice. Suitable laser coupling between these
      internal states leads to a uniform magnetic flux within the two-dimensional
      lattice. We show that this setup reproduces the main features of magnetic lattice
      systems, such as the fractal Hofstadter-butterfly spectrum and the chiral edge
      states of the associated Chern insulating phases. 

PMID- 24580446
TI  - How to observe coherent electron dynamics directly.
AB  - Detection of electron motion by elastic scattering of short x-ray pulses from a
      coherent superposition of highly excited electronic states in rare gas atoms is
      investigated. The laser excitation of the electron wave packet introduces strong
      anisotropy which facilitates detection, and large differences in the radial
      distribution of the excited Rydberg and core electrons allow the dynamics to be
      detected using both soft and hard x rays. 

PMID- 24580444
TI  - Experimental study of the two-body spin-orbit force in nuclei.
AB  - Energies and spectroscopic factors of the first 7/2-, 3/2-, 1/2-, and 5/2- states
      in the (35)Si21 nucleus were determined by means of the (d, p) transfer reaction
      in inverse kinematics at GANIL using the MUST2 and EXOGAM detectors. By comparing
      the spectroscopic information on the Si35 and S37 isotones, a reduction of the
      p3/2-p1/2 spin-orbit splitting by about 25% is proposed, while the f7/2-f5/2 spin
      orbit splitting seems to remain constant. These features, derived after having
      unfolded nuclear correlations using shell model calculations, have been
      attributed to the properties of the two-body spin-orbit interaction, the
      amplitude of which is derived for the first time in an atomic nucleus. The
      present results, remarkably well reproduced by using several realistic nucleon
      nucleon forces, provide a unique touchstone for the modeling of the spin-orbit
      interaction in atomic nuclei.

PMID- 24580447
TI  - Electronic energy dissipation during scattering of vibrationally excited
      molecules at metal surfaces: ab initio simulations for HCl/Al(111).
AB  - In this Letter, ab initio molecular dynamics simulations based on time-dependent
      density functional theory for the electrons and Ehrenfest dynamics for the nuclei
      are reported that detail the interaction of a vibrating HCl molecule with an
      Al(111) substrate. The mechanism responsible for the strong electron-hole-pair
      (EHP)-vibrational coupling in case of highly vibrationally excited molecules is
      traced back to a large eigenenergy shift of the spz*-like antibonding HCl lowest
      unoccupied molecular orbital with the bond length. As a consequence of this
      mechanism, the electronic excitation spectra turn out to be highly asymmetric.
      The simulations suggest an explanation of how to reconcile a strong EHP
      vibrational coupling in case of highly vibrationally excited molecules with the
      small, but clearly evident, electronic contribution to the v=0 -> v=1 vibrational
      excitation observed experimentally during the scattering of HCl molecules at a
      hot Au surface by Ran et al. [Phys. Rev. Lett. 98 237601 (2007)].

PMID- 24580448
TI  - Antiresonance phase shift in strongly coupled cavity QED.
AB  - We investigate phase shifts in the strong coupling regime of single-atom cavity
      quantum electrodynamics. On the light transmitted through the system, we observe
      a phase shift associated with an antiresonance and show that both its frequency
      and width depend solely on the atom, despite the strong coupling to the cavity.
      This shift is optically controllable and reaches 140 degrees --the largest ever
      reported for a single emitter. Our result offers a new technique for the
      characterization of complex integrated quantum circuits.

PMID- 24580449
TI  - Atomic Fock state preparation using Rydberg blockade.
AB  - We use coherent excitation of 3-16 atom ensembles to demonstrate collective Rabi
      flopping mediated by Rydberg blockade. Using calibrated atom number measurements,
      we quantitatively confirm the expected ?N Rabi frequency enhancement to within
      4%. The resulting atom number distributions are consistent with an essentially
      perfect blockade. We then use collective Rabi pi pulses to produce N=1, 2 atom
      number Fock states with fidelities of 62% and 48%, respectively. The N=2 Fock
      state shows the collective Rabi frequency enhancement without corruption from
      atom number fluctuations.

PMID- 24580450
TI  - Kinetic theory for transverse optomechanical instabilities.
AB  - We investigate transverse symmetry-breaking instabilities emerging from the
      optomechanical coupling between light and the translational degrees of freedom of
      a collisionless, damping-free gas of cold, two-level atoms. We develop a kinetic
      theory that can also be mapped on to the case of an electron plasma under
      ponderomotive forces. A general criterion for the existence and spatial scale of
      transverse instabilities is identified; in particular, we demonstrate that
      monotonically decreasing velocity distribution functions are always unstable. 

PMID- 24580452
TI  - Recurrent scattering and memory effect at the Anderson localization transition.
AB  - We report on ultrasonic measurements of the propagation operator in a strongly
      scattering mesoglass. The backscattered field is shown to display a deterministic
      spatial coherence due to a remarkably large memory effect induced by long
      recurrent trajectories. Investigation of the recurrent scattering contribution
      directly yields the probability for a wave to come back close to its starting
      spot. The decay of this quantity with time is shown to change dramatically near
      the Anderson localization transition. The singular value decomposition of the
      propagation operator reveals the dominance of very intense recurrent scattering
      paths near the mobility edge. 

PMID- 24580451
TI  - Using subwavelength diffraction gratings to design open electromagnetic cavities.
AB  - In this Letter we propose to use subwavelength diffraction gratings as very good
      semitransparent mirrors for electromagnetic waves to design open cavities. To do
      so, we replace part of the walls of a cavity by such a grating. We numerically
      and analytically link the grating characteristics to the spectral properties of
      the realized open cavity. Then we demonstrate that the eigenmodes of the cavity
      can be transmitted perfectly through the grating to the exterior, thereby turning
      a point source inside the cavity into a very directive source. We investigate the
      effect of disorder, which leads to isotropic radiation patterns, and perform
      experiments in the microwave domain in order to support our claims. Finally, we
      present an example of application of the concept in fundamental physics, by
      measuring from outside the eigenmodes of a disordered microwave cavity. 

PMID- 24580453
TI  - Unidirectional lasing emerging from frozen light in nonreciprocal cavities.
AB  - We introduce a class of unidirectional lasing modes associated with the frozen
      mode regime of nonreciprocal slow-wave structures. Such asymmetric modes can only
      exist in cavities with broken time-reversal and space inversion symmetries. Their
      lasing frequency coincides with a spectral stationary inflection point of the
      underlying passive structure and is virtually independent of its size. These
      unidirectional lasers can be indispensable components of photonic integrated
      circuitry. 

PMID- 24580454
TI  - Self-injection locking and phase-locked states in microresonator-based optical
      frequency combs.
AB  - Microresonator-based optical frequency combs have been a topic of extensive
      research during the last few years. Several theoretical models for the comb
      generation have been proposed; however, they do not comprehensively address
      experimental results that show a variety of independent comb generation
      mechanisms. Here, we present frequency-domain experiments that illuminate the
      transition of microcombs into phase-locked states, which show characteristics of
      injection locking between ensembles of comb modes. In addition, we demonstrate
      the existence of equidistant optical frequency combs that are phase stable but
      have nondeterministic phase relationships between individual comb modes. 

PMID- 24580455
TI  - Near-field thermal transistor.
AB  - Using a block of three separated solid elements, a thermal source and drain
      together with a gate made of an insulator-metal transition material exchanging
      near-field thermal radiation, we introduce a nanoscale analog of a field-effect
      transistor that is able to control the flow of heat exchanged by evanescent
      thermal photons between two bodies. By changing the gate temperature around its
      critical value, the heat flux exchanged between the hot body (source) and the
      cold body (drain) can be reversibly switched, amplified, and modulated by a tiny
      action on the gate. Such a device could find important applications in the domain
      of nanoscale thermal management and it opens up new perspectives concerning the
      development of contactless thermal circuits intended for information processing
      using the photon current rather than the electric current. 

PMID- 24580456
TI  - Solitons transport water through narrow carbon nanotubes.
AB  - Transformative technologies for desalination and chemical separations call for
      understanding molecular transport through man-made and biological nanochannels.
      Using numerical simulation of single-file flow of water through carbon nanotubes,
      we find that flow is due to fast-moving density variations (solitons) that are
      additive so flow rate is proportional to number of solitons. Simulation results
      match predictions from a theoretical model for soliton propagation. From 1-300 K
      flow rates increase as temperature decreases. Our results build a fundamentally
      new understanding of nanochannel flows and suggest new principles for the design
      of nanoscale devices. 

PMID- 24580457
TI  - Turbulent fluid acceleration generates clusters of gyrotactic microorganisms.
AB  - The motility of microorganisms is often biased by gradients in physical and
      chemical properties of their environment, with myriad implications on their
      ecology. Here we show that fluid acceleration reorients gyrotactic plankton,
      triggering small-scale clustering. We experimentally demonstrate this phenomenon
      by studying the distribution of the phytoplankton Chlamydomonas augustae within a
      rotating tank and find it to be in good agreement with a new, generalized model
      of gyrotaxis. When this model is implemented in a direct numerical simulation of
      turbulent flow, we find that fluid acceleration generates multifractal plankton
      clustering, with faster and more stable cells producing stronger clustering. By
      producing accumulations in high-vorticity regions, this process is fundamentally
      different from clustering by gravitational acceleration, expanding the range of
      mechanisms by which turbulent flows can impact the spatial distribution of active
      suspensions. 

PMID- 24580458
TI  - Increasing lifetimes and the growing saddles of shear flow turbulence.
AB  - In linearly stable shear flows, turbulence spontaneously decays with a
      characteristic lifetime that varies with Reynolds number. The lifetime sharply
      increases with Reynolds number so that a possible divergence marking the
      transition to sustained turbulence at a critical point has been discussed. We
      present a mechanism by which the lifetimes increase: in the system's state space,
      turbulent motion is supported by a chaotic saddle. Inside this saddle a locally
      attracting periodic orbit is created and undergoes a traditional bifurcation
      sequence generating chaos. The formed new "turbulent bubble" is initially an
      attractor supporting persistent chaotic dynamics. Soon after its creation, it
      collides with its own boundary, by which it becomes leaky and dynamically
      connected with the surrounding structures. The complexity of the chaotic saddle
      that supports transient turbulence hence increases by incorporating the remnant
      of a new bubble. As a a result, the time it takes for a trajectory to leave the
      saddle and decay to the laminar state is increased. We demonstrate this
      phenomenon in plane Couette flow and show that characteristic lifetimes vary
      nonsmoothly and nonmonotonically with Reynolds number.

PMID- 24580459
TI  - Experimental demonstration of electron longitudinal-phase-space linearization by
      shaping the photoinjector laser pulse.
AB  - Control of the electron-beam longitudinal-phase-space distribution is of crucial
      importance in a number of accelerator applications, such as linac-driven free
      electron lasers, colliders and energy recovery linacs. Some longitudinal-phase
      space features produced by nonlinear electron beam self- fields, such as a
      quadratic energy chirp introduced by geometric longitudinal wakefields in radio
      frequency (rf) accelerator structures, cannot be compensated by ordinary tuning
      of the linac rf phases nor corrected by a single high harmonic accelerating
      cavity. In this Letter we report an experimental demonstration of the removal of
      the quadratic energy chirp by properly shaping the electron beam current at the
      photoinjector. Specifically, a longitudinal ramp in the current distribution at
      the cathode linearizes the longitudinal wakefields in the downstream linac,
      resulting in a flat electron current and energy distribution. We present
      longitudinal-phase-space measurements in this novel configuration compared to
      those typically obtained without longitudinal current shaping at the FERMI linac.

PMID- 24580460
TI  - Seeding of self-modulation instability of a long electron bunch in a plasma.
AB  - We demonstrate experimentally that a relativistic electron bunch shaped with a
      sharp rising edge drives plasma wakefields with one to seven periods along the
      bunch as the plasma density is increased. The plasma density is varied in the
      10(15)-10(17)  cm(-3) range. The wakefields generation is observed after the
      plasma as a periodic modulation of the correlated energy spectrum of the incoming
      bunch. We choose a low bunch charge of 50 pC for optimum visibility of the
      modulation at all plasma densities. The longitudinal wakefields creating the
      modulation are in the MV/m range and are indirect evidence of the generation of
      transverse wakefields that can seed the self-modulation instability, although the
      instability does not grow significantly over the short plasma length (2 cm). We
      show that the seeding provides a phase reference for the wakefields, a necessary
      condition for the deterministic external injection of a witness bunch in an
      accelerator. This electron work supports the concept of similar experiments in
      the future, e.g., SMI experiments using long bunches of relativistic protons.

PMID- 24580462
TI  - Relativistic runaway ionization fronts.
AB  - We investigate the first example of self-consistent impact ionization fronts
      propagating at relativistic speeds and involving interacting, high-energy
      electrons. These fronts, which we name relativistic runaway ionization fronts,
      show remarkable features such as a bulk speed within less than one percent of the
      speed of light and the stochastic selection of high-energy electrons for further
      acceleration, which leads to a power-law distribution of particle energies. A
      simplified model explains this selection in terms of the overrun of Coulomb
      scattered electrons. Appearing as the electromagnetic interaction between
      electrons saturates the exponential growth of a relativistic runaway electron
      avalanche, relativistic runaway ionization fronts may occur in conjunction with
      terrestrial gamma-ray flashes and thus explain recent observations of long, power
      law tails in the terrestrial gamma-ray flash energy spectrum. 

PMID- 24580461
TI  - Observation of self-sustaining relativistic ionization wave launched by a sheath
      field.
AB  - We present experimental evidence supported by simulations of a relativistic
      ionization wave launched into a surrounding gas by the sheath field of a plasma
      filament with high energy electrons. Such a filament is created by irradiating a
      clustering gas jet with a short pulse laser (115  fs) at a peak intensity of
      5*10(17)  W/cm2. We observe an ionization wave propagating radially through the
      gas for about 2 ps at 0.2-0.5 c after the laser has passed, doubling the initial
      radius of the filament. The gas is ionized by the sheath field, while the
      longevity of the wave is explained by a moving field structure that traps the
      high energy electrons near the boundary, maintaining a strong sheath field
      despite the significant expansion of the plasma.

PMID- 24580463
TI  - Ground-state pressure of quasi-2D Fermi and Bose gases.
AB  - Using an ultracold gas of atoms, we have realized a quasi-two-dimensional Fermi
      system with widely tunable s-wave interactions nearly in a ground state. Pressure
      and density are measured. The experiment covers physically different regimes:
      weakly and strongly attractive Fermi gases and a Bose gas of tightly bound pairs
      of fermions. In the Fermi regime of weak interactions, the pressure is
      systematically above a Fermi-liquid-theory prediction, maybe due to mesoscopic
      effects. In the opposite Bose regime, the pressure agrees with a bosonic mean
      field scaling in a range beyond simplest expectations. In the strongly
      interacting regime, measurements disagree with a purely 2D model. Reported data
      may serve for sensitive testing of theoretical methods applicable across
      different quantum physics disciplines. 

PMID- 24580464
TI  - Condensate phase microscopy.
AB  - We show that the phase of a Bose-Einstein condensate wave function of ultracold
      atoms in an optical lattice potential in two dimensions can be detected. The time
      of-flight images, obtained in a free expansion of initially trapped atoms, are
      related to the initial distribution of atomic momenta but the information on the
      phase is lost. However, the initial atomic cloud is bounded and this information,
      in addition to the time-of-flight images, is sufficient in order to employ the
      phase retrieval algorithms. We analyze the phase retrieval methods for model wave
      functions in a case of a Bose-Einstein condensate in a triangular optical lattice
      in the presence of artificial gauge fields. 

PMID- 24580465
TI  - Structural evolution and medium range order in permanently densified vitreous
      SiO2.
AB  - Positron annihilation lifetime spectroscopy is employed to measure the size of
      the interstitial void spaces characterizing the structure of a set of permanently
      densified SiO2 glasses. The average volume of the voids is markedly affected by
      the densification process and linearly shrinks by almost an order of magnitude
      after a relative density variation of 22%. In addition, x-ray diffraction shows
      that this change of density does not modify appreciably the short range order,
      which remains organized in SiO4 tetrahedra. These results strongly suggest a
      porous medium description for v-SiO2 glasses where the compressibility and the
      medium range order are dominated by the density variation of the voids volume up
      to densities close to that of alpha-quartz. 

PMID- 24580466
TI  - Exploring the structural complexity of intermetallic compounds by an adaptive
      genetic algorithm.
AB  - Solving the crystal structures of novel phases with nanoscale dimensions
      resulting from rapid quenching is difficult due to disorder and competing
      polymorphic phases. Advances in computer speed and algorithm sophistication have
      now made it feasible to predict the crystal structure of an unknown phase without
      any assumptions on the Bravais lattice type, atom basis, or unit cell dimensions,
      providing a novel approach to aid experiments in exploring complex materials with
      nanoscale grains. This approach is demonstrated by solving a long-standing puzzle
      in the complex crystal structures of the orthorhombic, rhombohedral, and
      hexagonal polymorphs close to the Zr2Co11 intermetallic compound. From our
      calculations, we identified the hard magnetic phase and the origin of high
      coercivity in this compound, thus guiding further development of these materials
      for use as high performance permanent magnets without rare-earth elements. 

PMID- 24580467
TI  - Elastic-plastic-brittle transitions and avalanches in disordered media.
AB  - A spring lattice model with the ability to simulate elastic-plastic-brittle
      transitions in a disordered medium is presented. The model is based on bilinear
      constitutive law defined at the spring level and power-law-type disorder
      introduced in the yield and failure limits of the springs. The key parameters of
      the proposed model effectively control the disorder distribution, significantly
      affecting the stress-strain response, the damage accumulation process, and the
      fracture surfaces. The model demonstrates a plastic strain avalanche behavior for
      perfectly plastic as well as hardening materials with a power-law distribution,
      in agreement with the experiments and related models. The strength of the model
      is in its generality and ability to interpolate between elastic-plastic hardening
      and elastic-brittle transitions. 

PMID- 24580468
TI  - Measurement of enhanced radiation force on a parallel metallic-plate system in
      the microwave regime.
AB  - We measure the force exerted by microwave radiation on a centimeter-sized
      parallel-plate metallic resonant unit. By varying the ambient environment, we
      distinguish carefully between the direct radiation force and the indirect
      photothermal component. At the microwave resonance, the former is measured
      quantitatively to be 100 times larger than the conventional radiation force.
      Furthermore, the enhanced radiation force tends to increase the separation of the
      plates. Both the direction and the magnitude of the measured force agree well
      with numerical calculations. 

PMID- 24580469
TI  - Local vibrations and negative thermal expansion in ZrW2O8.
AB  - We present an x-ray pair distribution function (XPDF) analysis and extended x-ray
      absorption fine structure (EXAFS) data for ZrW2O8 (10-500 K) with a focus on the
      stiffness of the Zr-O-W linkage. The XPDF is highly sensitive to W-Zr and W-W
      correlations, but much less so to O-O or W-O correlations. The Zr-W peak in the
      XPDF data has a weak temperature dependence and, hence, this linkage is
      relatively stiff and does not permit bending of the Zr-O-W link. We propose that
      the low energy vibrational modes that lead to negative thermal expansion involve
      correlated rotations of ZrO6 octahedra that produce large <111> translations of
      the WO4 tetrahedra, rather than a transverse motion of O atoms that imply a
      flexible Zr-O-W linkage.

PMID- 24580438
TI  - Measurements of indirect CP asymmetries in D0 -> K- K+ and D0 -> pi- pi+ decays.
AB  - A study of indirect CP violation in D0 mesons through the determination of the
      parameter AGamma is presented using a data sample of pp collisions, corresponding
      to an integrated luminosity of 1.0  fb(-1), collected with the LHCb detector and
      recorded at the center-of-mass energy of 7 TeV at the LHC. The parameter AGamma
      is the asymmetry of the effective lifetimes measured in decays of D0 and D0
      mesons to the CP eigenstates K- K+ and pi- pi+. Fits to the data sample yield
      AGamma(KK)=(-0.35+/-0.62+/-0.12)*10(-3) and AGamma(pipi)=(0.33+/-1.06+/-0.14)*10(
      3), where the first uncertainties are statistical and the second systematic. The
      results represent the world's best measurements of these quantities. They show no
      difference in AGamma between the two final states and no indication of CP
      violation.

PMID- 24580440
TI  - Measurement of associated production of z bosons with charm quark jets in pp
      collisions at ?s=1.96  TeV.
AB  - We present the first measurements of the ratios of cross sections sigma(pp -> Z+c
      jet)/sigma(pp -> Z+jet) and sigma(pp -> Z+c jet)/sigma(pp -> Z+b jet) for the
      associated production of a Z boson with at least one charm or bottom quark jet.
      Jets have transverse momentum pT(jet)>20  GeV and pseudorapidity |eta(jet)|<2.5.
      These cross section ratios are measured differentially as a function of jet and Z
      boson transverse momenta, based on 9.7  fb(-1) of pp collisions collected with
      the D0 detector at the Fermilab Tevatron Collider at ?s=1.96  TeV. The
      measurements show significant deviations from perturbative QCD calculations and
      predictions from various event generators.

PMID- 24580470
TI  - Towards bond selective chemistry from first principles: methane on metal
      surfaces.
AB  - Controlling bond-selective chemical reactivity is of great importance and has a
      broad range of applications. Here, we present a molecular dynamics study of bond
      selective reactivity of methane and its deuterated isotopologues (i.e., CH(4
      x)D(x), x=0,1,2,3,4) on Ni(111) and Pt(111) from first principles calculations.
      Our simulations allow for reproducing the full C-H bond selectivity recently
      achieved experimentally via mode-specific vibrational excitation and explain its
      origin. Moreover, we also predict the hitherto unexplored influence of the
      molecular translational energy on such a selectivity as well as the conditions
      under which the full selectivity can be realized for the a priori less active C-D
      bond.

PMID- 24580471
TI  - Accurate and scalable O(N) algorithm for first-principles molecular-dynamics
      computations on large parallel computers.
AB  - We present the first truly scalable first-principles molecular dynamics algorithm
      with O(N) complexity and controllable accuracy, capable of simulating systems
      with finite band gaps of sizes that were previously impossible with this degree
      of accuracy. By avoiding global communications, we provide a practical
      computational scheme capable of extreme scalability. Accuracy is controlled by
      the mesh spacing of the finite difference discretization, the size of the
      localization regions in which the electronic wave functions are confined, and a
      cutoff beyond which the components of the overlap matrix can be omitted when
      computing selected elements of its inverse. We demonstrate the algorithm's
      excellent parallel scaling for up to 101,952 atoms on 23,328 processors, with a
      wall-clock time of the order of 1 min per molecular dynamics time step and
      numerical error on the forces of less than 7*10(-4)  Ha/Bohr.

PMID- 24580474
TI  - Quantum nature of edge magnetism in graphene.
AB  - It is argued that the subtle crossover from decoherence-dominated classical
      magnetism to fluctuation-dominated quantum magnetism is experimentally accessible
      in graphene nanoribbons. We show that the width of a nanoribbon determines
      whether the edge magnetism is on the classical side, on the quantum side, or in
      between. In the classical regime, decoherence is dominant and leads to static
      spin polarizations at the ribbon edges, which are well described by mean-field
      theories. The quantum Zeno effect is identified as the basic mechanism which is
      responsible for the spin polarization and thereby enables the application of
      graphene in spintronics. On the quantum side, however, the spin polarization is
      destroyed by dynamical processes. The great tunability of graphene magnetism thus
      offers a viable route for the study of the quantum-classical crossover. 

PMID- 24580472
TI  - Coherent excitonic coupling in an asymmetric double InGaAs quantum well arises
      from many-body effects.
AB  - We study an asymmetric double InGaAs quantum well using optical two-dimensional
      coherent spectroscopy. The collection of zero-quantum, one-quantum, and two
      quantum two-dimensional spectra provides a unique and comprehensive picture of
      the double well coherent optical response. Coherent and incoherent contributions
      to the coupling between the two quantum well excitons are clearly separated. An
      excellent agreement with density matrix calculations reveals that coherent
      interwell coupling originates from many-body interactions. 

PMID- 24580475
TI  - Topological phases in the zeroth Landau level of bilayer graphene.
AB  - We analyze the phase diagram of the zeroth Landau level of bilayer graphene,
      taking into account the realistic effects of screening of the Coulomb interaction
      and strong mixing between two degenerate sublevels. We identify robust quantum
      Hall states at filling factors nu=-1, -4/3, -5/3, -8/5, -1/2 and discuss the
      nature of their ground states, collective excitations, and relation to the more
      familiar states in GaAs using a tractable model. In particular, we present
      evidence that the nu=-1/2 state is non-Abelian and described by either the Moore
      Read wave function or its particle-hole conjugate, while ruling out other
      candidates such as the 331 state.

PMID- 24580473
TI  - Effects of spin-dependent interactions on polarization of bright polariton
      solitons.
AB  - We report on the spin properties of bright polariton solitons supported by an
      external pump to compensate losses. We observe robust circularly polarized
      solitons when a circularly polarized pump is applied, a result attributed to
      phase synchronization between nondegenerate TE and TM polarized polariton modes
      at high momenta. For the case of a linearly polarized pump, either sigma+ or
      sigma- circularly polarized bright solitons can be switched on in a controlled
      way by a sigma+ or sigma- writing beam, respectively. This feature arises
      directly from the widely differing interaction strengths between co- and cross
      circularly polarized polaritons. In the case of orthogonally linearly polarized
      pump and writing beams, the soliton emission on average is found to be
      unpolarized, suggesting strong spatial evolution of the soliton polarization. The
      observed results are in agreement with theory, which predicts stable circularly
      polarized solitons and unstable linearly polarized solitons. 

PMID- 24580476
TI  - Large-Chern-number quantum anomalous Hall effect in thin-film topological
      crystalline insulators.
AB  - We theoretically predict that thin-film topological crystalline insulators can
      host various quantum anomalous Hall phases when doped by ferromagnetically
      ordered dopants. Any Chern number between +/-4 can, in principle, be reached as a
      result of the interplay between (a) the induced Zeeman field, depending on the
      magnetic doping concentration, (b) the structural distortion, either intrinsic or
      induced by a piezoelectric material through the proximity effect, and (c) the
      thickness of the thin film. We propose a heterostructure to realize quantum
      anomalous Hall phases with Chern numbers that can be tuned by electric fields. 

PMID- 24580477
TI  - Interactions and charge fractionalization in an electronic Hong-Ou-Mandel
      interferometer.
AB  - We consider an electronic analog of the Hong-Ou-Mandel (HOM) interferometer,
      where two single electrons travel along opposite chiral edge states and collide
      at a quantum point contact. Studying the current noise, we show that because of
      interactions between copropagating edge states, the degree of
      indistinguishability between the two electron wave packets is dramatically
      reduced, leading to reduced contrast for the HOM signal. This decoherence
      phenomenon strongly depends on the energy resolution of the packets. Insofar as
      interactions cause charge fractionalization, we show that charge and neutral
      modes interfere with each other, leading to satellite dips or peaks in the
      current noise. Our calculations explain recent experimental results [E.
      Bocquillon Science 339 1054 (2013)] where an electronic HOM signal with reduced
      contrast was observed.

PMID- 24580478
TI  - Direct quantitative electrical measurement of many-body interactions in exciton
      complexes in InAs quantum dots.
AB  - We present capacitance-voltage spectra for the conduction band states of InAs
      quantum dots obtained under continuous illumination. The illumination leads to
      the appearance of additional charging peaks that we attribute to the charging of
      electrons into quantum dots containing a variable number of illumination-induced
      holes. By this we demonstrate an electrical measurement of excitonic states in
      quantum dots. Magnetocapacitance-voltage spectroscopy reveals that the electron
      always tunnels into the lowest electronic state. This allows us to directly
      extract, from the highly correlated many-body states, the correlation energy. The
      results are compared quantitatively to state of the art atomistic configuration
      interaction calculations, showing very good agreement for a lower level of
      excitations and also limitations of the approach for an increasing number of
      particles. Our experiments offer a rare benchmark to many-body theoretical
      calculations. 

PMID- 24580479
TI  - Fractional quantum Hall effect at nu=1/2 in hole systems confined to GaAs quantum
      wells.
AB  - We observe the fractional quantum Hall effect (FQHE) at the even-denominator
      Landau level filling factor nu=1/2 in two-dimensional hole systems confined to
      GaAs quantum wells of width 30 to 50 nm and having bilayerlike charge
      distributions. The nu=1/2 FQHE is stable when the charge distribution is
      symmetric and only in a range of intermediate densities, qualitatively similar to
      what is seen in two-dimensional electron systems confined to approximately twice
      wider GaAs quantum wells. Despite the complexity of the hole Landau level
      structure, originating from the coexistence and mixing of the heavy- and light
      hole states, we find the hole nu=1/2 FQHE to be consistent with a two-component,
      Halperin-Laughlin (Psi331) state. 

PMID- 24580480
TI  - Nematic susceptibility of hole-doped and electron-doped BaFe2As2 iron-based
      superconductors from shear modulus measurements.
AB  - The nematic susceptibility, chiphi, of hole-doped Ba(1-x)K(x)Fe2As2 and electron
      doped Ba(Fe(1-x)Co(x))2As2 iron-based superconductors is obtained from
      measurements of the elastic shear modulus using a three-point bending setup in a
      capacitance dilatometer. Nematic fluctuations, although weakened by doping,
      extend over the whole superconducting dome in both systems, suggesting their
      close tie to superconductivity. Evidence for quantum critical behavior of chiphi
      is, surprisingly, only found for Ba(Fe(1-x)Co(x))2As2 and not for Ba(1
      x)K(x)Fe2As2--the system with the higher maximal Tc value.

PMID- 24580481
TI  - Single-quasiparticle trapping in aluminum nanobridge Josephson junctions.
AB  - We present microwave measurements of a high quality factor superconducting
      resonator incorporating two aluminum nanobridge Josephson junctions in a loop
      shunted by an on-chip capacitor. Trapped quasiparticles (QPs) shift the resonant
      frequency, allowing us to probe the trapped QP number and energy distribution and
      to quantify their lifetimes. We find that the trapped QP population obeys a Gibbs
      distribution above 75 mK, with non-Poissonian trapping statistics. Our results
      are in quantitative agreement with the Andreev bound state model of transport,
      and demonstrate a practical means to quantify on-chip QP populations and validate
      mitigation strategies in a cryogenic environment. 

PMID- 24580482
TI  - Evidence of chiral order in the charge-ordered phase of superconducting
      La1.875Ba0.125Cuo4 single crystals using polar Kerr-effect measurements.
AB  - High resolution polar Kerr effect measurements were performed on
      La1.875Ba0.125CuO4 single crystals revealing that a finite Kerr signal is
      measured below an onset temperature TK that coincides with the charge ordering
      transition temperature TCO. We further show that the sign of the Kerr signal
      cannot be trained with the magnetic field, is found to be the same on opposite
      sides of the same crystal, and is odd with respect to strain in the diagonal
      direction of the unit cell. These observations are consistent with a chiral
      "gyrotropic" order above Tc for La1.875Ba0.125CuO4; similarities to other
      cuprates suggest that it is a universal property in the pseudogap regime. 

PMID- 24580483
TI  - Evidence of a nonequilibrium distribution of quasiparticles in the microwave
      response of a superconducting aluminum resonator.
AB  - In a superconductor, absorption of photons with an energy below the
      superconducting gap leads to redistribution of quasiparticles over energy and
      thus induces a strong nonequilibrium quasiparticle energy distribution. We have
      measured the electrodynamic response, quality factor, and resonant frequency of a
      superconducting aluminium microwave resonator as a function of microwave power
      and temperature. Below 200 mK, both the quality factor and resonant frequency
      decrease with increasing microwave power, consistent with the creation of excess
      quasiparticles due to microwave absorption. Counterintuitively, above 200 mK, the
      quality factor and resonant frequency increase with increasing power. We
      demonstrate that the effect can only be understood by a nonthermal quasiparticle
      distribution. 

PMID- 24580484
TI  - Local inhomogeneity and filamentary superconductivity in Pr-doped CaFe2As2.
AB  - We use multiscale techniques to determine the extent of local inhomogeneity and
      superconductivity in Ca0.86Pr0.14Fe2As2 single crystal. The inhomogeneity is
      manifested as a spatial variation of the praseodymium concentration, local
      density of states, and superconducting order parameter. We show that the high-Tc
      superconductivity emerges from cloverlike defects associated with Pr dopants. The
      highest Tc is observed in both the tetragonal and collapsed tetragonal phases,
      and its filamentary nature is a consequence of nonuniform Pr distribution that
      develops localized, isolated superconducting regions within the crystals. 

PMID- 24580486
TI  - Magnetic-field-induced ferroelectric polarization reversal in the multiferroic
      Ge(1-x)Mn(x)Te semiconductor.
AB  - Ge(1-x)Mn(x)Te is shown to be a multiferroic semiconductor, exhibiting both
      ferromagnetic and ferroelectric properties. By ferromagnetic resonance we
      demonstrate that both types of order are coupled to each other. As a result,
      magnetic-field-induced ferroelectric polarization reversal is achieved. Switching
      of the spontaneous electric dipole moment is monitored by changes in the
      magnetocrystalline anisotropy. This also reveals that the ferroelectric
      polarization reversal is accompanied by a reorientation of the hard and easy
      magnetization axes. By tuning the GeMnTe composition, the interplay between
      ferromagnetism and ferroelectricity can be controlled.

PMID- 24580485
TI  - Confined dissipative droplet solitons in spin-valve nanowires with perpendicular
      magnetic anisotropy.
AB  - Magnetic dissipative droplets are localized, strongly nonlinear dynamical modes
      excited in nanocontact spin valves with perpendicular magnetic anisotropy. These
      modes find potential application in nanoscale structures for magnetic storage and
      computation, but dissipative droplet studies have so far been limited to extended
      thin films. Here, numerical and asymptotic analyses are used to demonstrate the
      existence and properties of novel solitons in confined structures. As a
      nanowire's width is decreased with a nanocontact of fixed size at its center, the
      observed modes undergo transitions from a fully localized two-dimensional droplet
      into a two-dimensional droplet edge mode and then a pulsating one-dimensional
      droplet. These solitons are interpreted as dissipative versions of classical,
      conservative solitons, allowing for an analytical description of the modes and
      the mechanisms of bifurcation. The presented results open up new possibilities
      for the study of low-dimensional solitons and droplet applications in
      nanostructures. 

PMID- 24580487
TI  - Designing a spin-Seebeck diode.
AB  - Using micromagnetic simulations, we have investigated spin dynamics in a spin
      valve bilayer in the presence of a thermal gradient. The direction and the
      intensity of the gradient allow us to excite the spin wave modes of each layer
      selectively. This permits us to synchronize the magnetization precession of the
      two layers and to rectify the flows of energy and magnetization through the
      system. Our study yields promising opportunities for applications in spin
      caloritronics and nanophononics devices. 

PMID- 24580488
TI  - Parity effects in 120 degrees  spin spirals.
AB  - The magnetic ground state of biatomic Fe chains on the reconstructed (5*1)
      Ir(001) surface is a cycloidal 120 degrees  spin spiral. Spin-resolved scanning
      tunneling microscopy reveals a striking variation of magnetic field dependences
      among the chains, which we attribute to parity effects resulting from finite
      lengths. Numerical simulations show that the chains are divided in three symmetry
      classes with the exact number of atoms in the chain determining the size and
      direction of their net magnetic moment. In contrast to antiferromagnetic systems,
      the three-atom periodicity causes the effective anisotropy to alternate between
      out of plane, in plane, and quenched. 

PMID- 24580489
TI  - Carrier and polarization dynamics in monolayer MoS2.
AB  - In monolayer MoS2, optical transitions across the direct band gap are governed by
      chiral selection rules, allowing optical valley initialization. In time-resolved
      photoluminescence (PL) experiments, we find that both the polarization and
      emission dynamics do not change from 4 to 300 K within our time resolution. We
      measure a high polarization and show that under pulsed excitation the emission
      polarization significantly decreases with increasing laser power. We find a fast
      exciton emission decay time on the order of 4 ps. The absence of a clear PL
      polarization decay within our time resolution suggests that the initially
      injected polarization dominates the steady-state PL polarization. The observed
      decrease of the initial polarization with increasing pump photon energy hints at
      a possible ultrafast intervalley relaxation beyond the experimental ps time
      resolution. By compensating the temperature-induced change in band gap energy
      with the excitation laser energy, an emission polarization of 40% is recovered at
      300 K, close to the maximum emission polarization for this sample at 4 K. 

PMID- 24580490
TI  - Infrared- and Raman-spectroscopy measurements of a transition in the crystal
      structure and a closing of the energy gap of BiTeI under pressure.
AB  - BiTeI is a giant Rashba spin splitting system, in which a noncentrosymmetric
      topological phase has recently been suggested to appear under high pressure. We
      investigated the optical properties of this compound, reflectivity and
      transmission, under pressures up to 15 GPa. The gap feature in the optical
      conductivity vanishes above p~9  GPa and does not reappear up to at least 15 GPa.
      The plasma edge, associated with intrinsically doped charge carriers, is smeared
      out through a phase transition at 9 GPa. Using high-pressure Raman spectroscopy,
      we follow the vibrational modes of BiTeI, providing additional clear evidence
      that the transition at 9 GPa involves a change of crystal structure. This change
      of crystal structure possibly inhibits the high-pressure topological phase from
      occurring. 

PMID- 24580491
TI  - Electroluminescence of a polythiophene molecular wire suspended between a
      metallic surface and the tip of a scanning tunneling microscope.
AB  - The electroluminescence of a polythiophene wire suspended between a metallic
      surface and the tip of a scanning tunneling microscope is reported. Under
      positive sample voltage, the spectral and voltage dependencies of the emitted
      light are consistent with the fluorescence of the wire junction mediated by
      localized plasmons. This emission is strongly attenuated for the opposite
      polarity. Both emission mechanism and polarity dependence are similar to what
      occurs in organic light emitting diodes (OLED) but at the level of a single
      molecular wire. 

PMID- 24580492
TI  - Electronic properties and metrology applications of the diamond NV- center under
      pressure.
AB  - The negatively charged nitrogen-vacancy (NV-) center in diamond has realized new
      frontiers in quantum technology. Here, the optical and spin resonances of the NV-
      center are observed under hydrostatic pressures up to 60 GPa. Our results
      motivate powerful new techniques to measure pressure and image high-pressure
      magnetic and electric phenomena. Additionally, molecular orbital analysis and
      semiclassical calculations provide insight into the effects of compression on the
      electronic orbitals of the NV- center. 

PMID- 24580493
TI  - Statistical mechanics and shape transitions in microscopic plates.
AB  - Unlike macroscopic multistable mechanical systems such as snap bracelets or
      elastic shells that must be physically manipulated into various conformations,
      microscopic systems can undergo spontaneous conformation switching between
      multistable states due to thermal fluctuations. Here we investigate the
      statistical mechanics of shape transitions in small elastic elliptical plates and
      shells driven by noise. By assuming that the effects of edges are small, which we
      justify exactly for plates and shells with a lenticular section, we decompose the
      shapes into a few geometric modes whose dynamics are easy to follow. We use Monte
      Carlo simulations to characterize the shape transitions between conformational
      minimal as a function of noise strength, and corroborate our results using a
      Fokker-Planck formalism to study the stationary distribution and the mean first
      passage time problem. Our results are applicable to objects such as graphene
      flakes or protein beta sheets, where fluctuations, geometry, and finite size
      effects are important. 

PMID- 24580494
TI  - Localized orientational order chaperones the nucleation of rotator phases in hard
      polyhedral particles.
AB  - The nucleation kinetics of the rotator phase in hard cuboctahedra, truncated
      octahedra, and rhombic dodecahedra is simulated via a combination of forward flux
      sampling and umbrella sampling. For comparable degrees of supersaturation, the
      polyhedra are found to have significantly lower free-energy barriers and faster
      nucleation rates than hard spheres. This difference primarily stems from
      localized orientational ordering, which steers polyhedral particles to pack more
      efficiently. Orientational order hence fosters here the growth of orientationally
      disordered nuclei. 

PMID- 24580495
TI  - Excluded volume causes integer and fractional plateaus in colloidal ratchet
      currents.
AB  - We study the collective transport of paramagnetic colloids driven above a
      magnetic bubble lattice by an external rotating magnetic field. We measure a
      direct ratchet current which rises in integer and fractional steps with the field
      amplitude. The stepwise increase is caused by excluded volume interactions
      between the particles, which form composite clusters above the bubbles with
      mobile and immobile occupation sites. Transient energy minima located at the
      interstitials between the bubbles cause the colloids to hop from one composite
      cluster to the next with synchronous and period doubled modes of transport. The
      colloidal current may be polarized to make selective use of type up or type down
      interstitials. 

PMID- 24580496
TI  - Competition-induced criticality in a model of meme popularity.
AB  - Heavy-tailed distributions of meme popularity occur naturally in a model of meme
      diffusion on social networks. Competition between multiple memes for the limited
      resource of user attention is identified as the mechanism that poises the system
      at criticality. The popularity growth of each meme is described by a critical
      branching process, and asymptotic analysis predicts power-law distributions of
      popularity with very heavy tails (exponent alpha<2, unlike preferential
      attachment models), similar to those seen in empirical data. 

PMID- 24580497
TI  - Comment on "Cooling by heating: refrigeration powered by photons".

PMID- 24580498
TI  - Comment on "Charge-density wave and superconducting dome in TiSe2 from electron
      phonon interaction".

PMID- 24580499
TI  - Calandra and Mauri reply.

PMID- 24580500
TI  - Comment on "Repulsive contact interactions make jammed particulate systems
      inherently nonharmonic".

PMID- 24580501
TI  - Histological detection of catalytic ferrous iron with the selective turn-on
      fluorescent probe RhoNox-1 in a Fenton reaction-based rat renal carcinogenesis
      model.
AB  - Iron overload of a chronic nature has been associated with a wide variety of
      human diseases, including infection, carcinogenesis, and atherosclerosis.
      Recently, a highly specific turn-on fluorescent probe (RhoNox-1) specific to
      labile ferrous iron [Fe(II)], but not to labile ferric iron [Fe(III)], was
      developed. The evaluation of Fe(II) is more important than Fe(III) in vivo in
      that Fe(II) is an initiating component of the Fenton reaction. In this study, we
      applied this probe to frozen sections of an established Fenton reaction-based rat
      renal carcinogenesis model with an iron chelate, ferric nitrilotriacetate (Fe
      NTA), in which catalytic iron induces the Fenton reaction specifically in the
      renal proximal tubules, presumably after iron reduction. Notably, this probe
      reacted with Fe(II) but with neither Fe(II)-NTA, Fe(III) nor Fe(III)-NTA in
      vitro. Prominent red fluorescent color was explicitly observed in and around the
      lumina of renal proximal tubules 1 h after an intraperitoneal injection of 10-35
      mg iron/kg Fe-NTA, which was dose-dependent, according to semiquantitative
      analysis. The RhoNox-1 signal colocalized with the generation of hydroxyl
      radicals, as detected by hydroxyphenyl fluorescein (HPF). The results demonstrate
      the transformation of Fe(III)-NTA to Fe(II) in vivo in the Fe-NTA-induced renal
      carcinogenesis model. Therefore, this probe would be useful for localizing
      catalytic Fe(II) in studies using tissues.

PMID- 24580502
TI  - Determining the anxiety and depression levels of pre-dialysis patients in eastern
      Turkey.
AB  - BACKGROUND: This study aimed to characterize the onset of psychopathological
      manifestations before dialysis in patients with chronic renal disease, thus
      contributing to the nursing care of these patients. SUBJECTS AND METHODS: A total
      of 120 patients registered at the Ataturk University Medical School who fulfilled
      the eligibility criteria and provided informed consent were included in this
      study. RESULTS: The majority of the participants, 63.4% were female, 50.0% were
      39 years of age or older, 70.0% were married, 80.0% had no current occupation,
      56.7% were high school graduates, and 48.3% did not know the cause of their
      disease. As indicated, 35.0% of the subjects had a depression score over the
      threshold level, with an average score of 8.53 +/- 2.45, while patients with
      scores over the threshold for anxiety made up 53.4%, with an average score of
      11.45 +/- 3.56. CONCLUSION: This study shows the presence of psychopathological
      problems before patients are started on dialysis. Therefore, nurses may alleviate
      pre-dialysis patients' fears and provide the necessary support to cope with
      anxiety and depression, thereby raising the patients' quality of life.

PMID- 24580504
TI  - Accelerating the introduction of rotavirus immunization in Indonesia.
AB  - The introduction of the rotavirus vaccine in Indonesia is currently in its
      infancy. Delay in its development might be caused by factors related to the
      perceived value of the vaccine, health system characteristics and policy
      considerations. Other factors, which may also interfere with optimizing the
      introduction, are financial barriers because Indonesia is a lower-middle-income
      country. Creating fiscal space to finance new immunization programs, such as for
      the rotavirus immunization, is very important to ensure the sustainability of new
      programs so that such programs would be financed over the long term and not
      endanger the sustainability of the Indonesian government's financial position.
      This article provides an illustration of the various steps needed to accelerate
      the introduction of the rotavirus immunization. 

PMID- 24580505
TI  - Registering eye movements during reading in Alzheimer's disease: difficulties in
      predicting upcoming words.
AB  - Reading requires the fine integration of attention, ocular movements, word
      identification, and language comprehension, among other cognitive parameters.
      Several of the associated cognitive processes such as working memory and semantic
      memory are known to be impaired by Alzheimer's disease (AD). This study analyzes
      eye movement behavior of 18 patients with probable AD and 40 age-matched controls
      during Spanish sentence reading. Controls focused mainly on word properties and
      considered syntactic and semantic structures. At the same time, controls'
      knowledge and prediction about sentence meaning and grammatical structure are
      quite evident when we consider some aspects of visual exploration, such as word
      skipping, and forward saccades. By contrast, in the AD group, the predictability
      effect of the upcoming word was absent, visual exploration was less focused,
      fixations were much longer, and outgoing saccade amplitudes were smaller than
      those in controls. The altered visual exploration and the absence of a contextual
      predictability effect might be related to impairments in working memory and long
      term memory retrieval functions. These eye movement measures demonstrate
      considerable sensitivity with respect to evaluating cognitive processes in
      Alzheimer's disease. They could provide a user-friendly marker of early disease
      symptoms and of its posterior progression. 

PMID- 24580507
TI  - The power of systems thinking in medicine.

PMID- 24580503
TI  - Annual research review: Child and adolescent mental health interventions: a
      review of progress in economic studies across different disorders.
AB  - BACKGROUND: Resources for supporting children and adolescents with psychiatric
      disorders continue to be scarce. Economics research can identify current patterns
      of expenditure, and help inform allocation of treatment and support resources
      between competing needs or uses. SCOPE AND METHODS: The aim was to identify the
      costs of supporting children and adolescents, the economic impacts of childhood
      psychiatric disorders in adulthood and any new evidence on the cost-effectiveness
      of interventions. An electronic search of databases (including PubMed, Medline
      and Psychinfo) identified peer-reviewed journal articles published between 2005
      and 2012. FINDINGS: Sixty-seven papers provided data on support and treatment
      costs now or in the future, or cost-effectiveness analyses of services. Half the
      articles came from the United States. Most articles focussed on autism spectrum
      disorder (ASD; 23 articles), attention deficit hyperactivity disorder (ADHD; n =
      15), conduct disorder (CD; n = 7), and anxiety or depression (n = 8). CONCLUSION:
      Only 14 studies used a cost perspective wider than health care; most included
      education costs (n = 11), but only five included costs to the justice system. The
      number of studies estimating costs to the family has increased, particularly for
      children with autism spectrum disorder (ASD). In the United Kingdom, support
      costs for children and adolescents with conduct disorder (CD) appear to be lower
      than for those with attention deficit hyperactivity disorder (ADHD), although for
      the United States, the opposite may be true. Support costs for children and
      adolescents with ASD may be higher than both CD and ADHD. However, there were
      many differences between the samples and the methods employed making comparisons
      between studies difficult. Outcomes in adulthood include negative impacts on
      (mental) health, quality of life, public sector services, employment status and
      income. The evidence base is improving for child and adolescent psychiatric
      disorders, although only one full cost-effectiveness analysis was identified
      since the previous review published in 2012. However, we still do not know enough
      about the economic implications of support and treatment for specific disorders.

PMID- 24580506
TI  - Systemic delivery of alpha-asarone with Kolliphor HS 15 improves its safety and
      therapeutic effect on asthma.
AB  - The commercially available alpha-asarone injections (CA-ARE) were frequently
      found to cause severe anaphylactic reactions by the solubilizer contained in the
      formulation such as polysorbate 80 and propylene glycol. This study aimed to
      develop a new ARE injection using Kolliphor HS 15 as solubilizing agent (HS 15
      ARE) by the dissolution method to resolve its poor solubility problem and reduce
      the anaphylaxis of CA-AREs caused by Polysorbate 80. The HS 15-ARE micelle showed
      a homogeneous round shape with the mean particle size of around 13.73 +/- 0.02
      nm, polydisperse index (PDI) of 0.19 +/- 0.01 and solubilizing efficiency of
      95.7% +/- 2.4%. In vitro and in vivo studies showed that HS 15-ARE is a stable
      injection presenting the same pharmacokinetic profile with CA-ARE. Moreover,
      improved therapeutic effect was observed for HS 15-ARE in treating asthma
      compared to CA-ARE (p < 0.05) with no anaphylactic reactions observed. These
      results demonstrate that the new formulation of ARE (HS 15-ARE) has a great
      potential for replacing CA-AREs injections.

PMID- 24580508
TI  - Age, CKD and other kidney messages.

PMID- 24580509
TI  - Learning by MOOC or by crook.

PMID- 24580510
TI  - From NPS MedicineWise.

PMID- 24580511
TI  - Self-regulation of autologous cell therapies.

PMID- 24580512
TI  - Lack of appropriate imaging before breast augmentation can have serious patient
      consequences.

PMID- 24580513
TI  - Dear Minister, please save yourself from activity-based funding.

PMID- 24580514
TI  - Opting in for opt-out consent.

PMID- 24580515
TI  - The need for a chiropractic adverse events reporting system in Australia.

PMID- 24580516
TI  - Inadvertent dispensing of Coumadin instead of Coversyl.

PMID- 24580519
TI  - Taking the inferior out of inferior vena cava filter follow-up.

PMID- 24580517
TI  - Population-based genetic carrier screening for cystic fibrosis in Victoria.

PMID- 24580520
TI  - Renal sympathetic denervation for resistant hypertension in a patient with a
      single kidney.

PMID- 24580521
TI  - Finally . . . an evidence-based tool to find primary health care evidence.

PMID- 24580522
TI  - Methylisothiazolinone in baby wipes: a rising star among causes of contact
      dermatitis.

PMID- 24580523
TI  - Harms unknown: health uncertainties cast doubt on the role of unconventional gas
      in Australia's energy future.
AB  - There is a push to increase production of unconventional gas in Australia, which
      would intensify the use of the controversial technique of hydraulic fracturing.
      The uncertainties surrounding the health implications of unconventional gas, when
      considered together with doubts surrounding its greenhouse gas profile and cost,
      weigh heavily against proceeding with proposed future developments. The health
      and environmental impacts of hydraulic fracturing have been the source of
      widespread public concern. A review of available literature shows a considerable
      degree of uncertainty, but an emerging consensus about the main risks. Gas is
      often claimed to be a less climate-damaging alternative to coal; however, this is
      called into question by the fugitive emissions produced by unconventional gas
      extraction and the consequences of its export. While the health effects
      associated with fracturing chemicals have attracted considerable public
      attention, risks posed by wastewater, community disruption and the interaction
      between exposures are of also of concern. The health burdens of unconventional
      gas are likely to fall disproportionately on rural communities, the young and the
      elderly. While the health and environmental risks and benefits must be compared
      with other energy choices, coal provides a poor benchmark. 

PMID- 24580524
TI  - Evaluation of the impact of National Breast Cancer Foundation-funded research.
AB  - OBJECTIVE: To evaluate the impact of the National Breast Cancer Foundation's
      (NBCF's) research investment. DESIGN AND PARTICIPANTS: Surveys based on the
      Payback Framework were sent to chief investigators involved in research funded by
      the NBCF during 1995-2012; a bibliometric analysis of NBCF-funded publications in
      2006-2010 was conducted; and a purposive, stratified sample of case studies was
      obtained. MAIN OUTCOME MEASURES: Research impact on knowledge production, the
      research system, informing policy, product development and broader health and
      economic benefits. RESULTS: Of 242 surveys sent, 153 (63%) were returned. The
      average impact of journals in which NBCF publications appeared was double that of
      world publications. Seventy surveys (46%) reported career progression, and 185
      higher degrees were obtained or expected, including 121 PhDs. One hundred and one
      grants (66%) produced tools that built capacity across the research system, and
      research teams leveraged an additional $1.40 in funding for every dollar
      invested. Fifteen applied grants and one basic grant impacted on policy. Ten
      basic and four applied grants led to the development of drugs, prognostic tools
      or diagnostic technologies. Twenty applied and two basic grants led to changes in
      practice and behaviour of health care staff, consumers and the public, with
      further impacts anticipated. Case studies provided illustrations of high impact.
      CONCLUSIONS: NBCF's strategy of investing in a mixed portfolio of research areas
      and mechanisms encouraged a broad range of impacts across all Payback categories.
      The impacts from basic research tended to focus on knowledge production and drug
      development; while applied research generated greater impacts within the other
      Payback categories. The funding of shared infrastructure stimulated impact across
      the research system.

PMID- 24580525
TI  - Clenbuterol toxicity: a NSW poisons information centre experience.
AB  - OBJECTIVE: To describe the epidemiology and toxicity of clenbuterol in exposures
      reported to the NSW Poisons Information Centre (NSWPIC). DESIGN AND SETTING:
      Retrospective observational study analysing data from all calls about clenbuterol
      exposure recorded in the NSWPIC database from 1 January 2004 to 31 December 2012.
      The NSWPIC coversthe Australian jurisdictions New South Wales, Tasmania and the
      Australian Capital Territory 24 hours a day and provides after-hours cover for
      the rest of Australia for 7 nights each fortnight. MAIN OUTCOME MEASURES: Total
      number of exposures, source of call (hospital, health care worker, member of the
      public), time from exposure to call, reasons for drug use, clinical features and
      advice given. RESULTS: Callers reported 63 exposures to clenbuterol, with a
      dramatic increase from three in 2008 to 27 in 2012. Of the 63 calls, 35 were from
      hospital, two from paramedics, one from general practice and 21 direct from the
      public. At least 53 patients (84%) required hospitalisation. The commonest
      reasons for use were bodybuilding and slimming. The most common features were
      tachycardia (24 patients), gastrointestinal disturbance (16) and tremor (11).
      Exposure was also associated with cardiotoxicity including one cardiac arrest in
      a 21-year-old man. CONCLUSION: Although a well recognised doping issue among
      elite athletes, clenbuterol use has spread out into the general public,
      especially during 2012, and should be considered in patients using bodybuilding
      or slimming products who present with protracted sympathomimetic features. The
      potential for misuse of this substance requires reconsideration of its current
      poison schedule registration and its availability.

PMID- 24580526
TI  - Vision screening in preschoolers: the New South Wales Statewide Eyesight
      Preschooler Screening program.
AB  - OBJECTIVE: To evaluate screening and diagnostic outcomes of the New South Wales
      Statewide Eyesight Preschooler Screening (StEPS) program, a state-funded,
      universal vision screening program for 4-year-old children. DESIGN, SETTING AND
      PARTICIPANTS: A cross-sectional evaluation of the StEPS program, in which
      eligible 4-year-old children were offered a vision screen in local health
      districts in NSW, between 1 July 2010 and 30 June 2011. MAIN OUTCOME MEASURES:
      Number and proportion of eligible children who were offered screening; accepted
      screening; were screened and scored a pass or were referred (routinely or
      urgently) for further vision assessment; and were referred for further assessment
      and required intervention. RESULTS: Of 91 324 eligible 4-year-olds in NSW, 80 328
      (88.0%) were offered screening, and 65 834 (72.1% of the eligible population)
      were screened. Of the children who were screened, 3867 (5.9%) scored less than
      6/9-2 but better than 6/18 in one or both eyes and were referred to their general
      practitioner or eye health professional for further vision assessment. A further
      1425 children (2.2%) scored 6/18 or less in one or both eyes and were referred
      for high-priority assessment. In the two local health districts with the most
      complete follow-up data, 704 of 779 children (90.4%) with routine referrals and
      278 of 285 (97.5%) with high-priority referrals required treatment or review at a
      later date. CONCLUSIONS: The StEPS program has achieved a high screening
      participation rate in NSW. Many children have been diagnosed and received
      treatment for previously undetected serious vision disorders that may otherwise
      have been diagnosed too late for effective intervention.

PMID- 24580528
TI  - The cat and the nap.

PMID- 24580527
TI  - Renal replacement therapy associated with lithium nephrotoxicity in Australia.
AB  - OBJECTIVE: To analyse the annual incidence of end-stage renal disease (ESRD)
      associated with lithium-induced nephropathy (LiN) in Australia. DESIGN, SETTING
      AND PARTICIPANTS: Retrospective cohort study of patients commencing renal
      replacement therapy (RRT) in Australia. We compared patients with LiN with all
      other RRT patients between 1 January 1991 and 31 December 2011, using Australia
      and New Zealand Dialysis and Transplant Registry data. MAIN OUTCOME MEASURES:
      Numbers and characteristics of incident RRT patients, primary kidney disease (LiN
      or other, based on clinical diagnosis). RESULTS: LiN contributed to 187 people in
      Australia commencing RRT between 1 January 1991 and 31 December 2011. The
      incidence rate increased from 0.14 cases/million population/year (95% CI, 0.06
      0.22) in 1992-1996 to 0.78 (95% CI, 0.67-0.90) in 2007-2011. This increase is
      unlikely to be attributed solely to demographic changes in Australia. LiN
      patients were more likely than non-LiN patients to be women, to be white, to
      smoke, and to have a higher body mass index, but were less likely to have
      undergone renal biopsy. CONCLUSIONS: Rates of ESRD attributed to LiN are
      increasing rapidly. Currently accepted lithium dosages and duration of treatment
      might induce ESRD in a large cohort of patients. We encourage clinicians to
      exercise discretion when prescribing lithium, check renal function regularly,
      stop lithium if there is a deterioration in two consecutive readings, and
      consider substitution with other drugs.

PMID- 24580529
TI  - A functional dependence? A social history of the medical use of morphine in
      Australia.

PMID- 24580530
TI  - Dissipative dynamics of two-level systems in low temperature glasses.
AB  - An approach based on a non-Markovian time-convolutionless polaron master equation
      is used to probe dynamics of a central chromophore embedded in a bath of two
      level systems commonly found in low-temperature glasses. By treating the
      Hamiltonian in the polaron frame, we can account for initial nonequilibrium bath
      states as well as the spatially correlated environmental effect. Relevant
      realistic situations are explored by adopting parameters from previous
      experiments. It is found that the temperature of the boson bath has a substantial
      effect on the population relaxation and the decoherence process, and a higher
      temperature also results in a higher saturation value of the entanglement
      entropy, while the coupling between the chromophore and the TLS has an effect
      that goes counter to that of the temperature. 

PMID- 24580531
TI  - Differences in conformational dynamics between Plasmodium falciparum and human
      Hsp90 orthologues enable the structure-based discovery of pathogen-selective
      inhibitors.
AB  - The high sequence conservation of druggable pockets of closely related proteins
      can make it challenging to develop selective inhibitors. We designed a new drug
      discovery approach that exploits both the static and dynamic differences of two
      orthologues. We applied it, as a proof of concept, to identify compounds that
      discriminate between the molecular chaperone Hsp90 of the protozoan pathogen
      Plasmodium falciparum (Pf) and that of its human host. We found that the ATP
      binding pocket has a Pf-specific extension, whose sequence lining is identical in
      human Hsp90 but which differs by tertiary structure and dynamics. Using these
      insights for a structure-based drug screen, we discovered novel 7-azaindole
      compounds that exclusively bind the recombinant N-terminal domain of PfHsp90 but
      not of human Hsp90 nor of a PfHsp90 mutant with "human-like" dynamics. Moreover,
      these compounds preferentially inhibit the growth of yeast complemented by
      PfHsp90 and block the growth of Pf in culture. 

PMID- 24580533
TI  - Synergistic stiffening in double-fiber networks.
AB  - Many biological materials are composite structures, interpenetrating networks of
      different types of fibers. The composite nature of such networks leads to
      superior mechanical properties, but the origin of this mechanical synergism is
      still poorly understood. Here we study soft composite networks, made by mixing
      two self-assembling fiber-forming components. We find that the elastic moduli of
      the composite networks significantly exceed the sum of the moduli of the two
      individual networks. This mechanical enhancement is in agreement with recent
      simulations, where it was attributed to a suppression of non-affine deformation
      modes in the most rigid fiber network due to the reaction forces in the softer
      network. The increase in affinity also causes a loss of strain hardening and an
      increase in the critical stress and stain at which the network fails. 

PMID- 24580534
TI  - Retraction of Desai, et al. Tissue Engineering, Part A, 19;1/2:40-48.

PMID- 24580532
TI  - Recombinant human lipocalin 2 acts as an antibacterial agent to prevent platelet
      contamination.
AB  - BACKGROUND: Bacterial contamination of platelet products is the major infectious
      risk in blood transfusion medicine, which can result in life-threatening sepsis
      in recipient. Lipocalin 2 (Lcn2) is an iron-sequestering protein in the
      antibacterial innate immune response, which inhibit bacterial growth. This study
      was aimed to evaluate the antibacterial property of Lcn2 in preventing bacterial
      contamination of platelets. METHODS: Recombinant Lcn2 was expressed in a
      eukaryotic expression system and following purification and characterization of
      the recombinant Lcn2, its minimum inhibitory concentration was determined. Then,
      platelet concentrates were inoculated with various concentrations of
      Staphylococcus epidermidis, Pseudomonas aeruginosa, Klebsiella pneumoniae,
      Escherichia coli, and Enterococcus faecalis, and the antibacterial effects of
      Lcn2 was evaluated at 20-24  degrees C. RESULTS: Results revealed that Lcn2
      effectively inhibited the growth of 1.5 * 10(4) CFU/ml S. epidermidis, P.
      aeruginosa, K. pneumoniae, E. coli, and E. faecalis at 40 ng/ml. At this
      concentration, Lcn2 also inhibited the growth of 1.5 * 10(3) CFU/ml
      Staphylococcus aureus and Proteus mirabilis. CONCLUSION: Recombinant Lcn2
      inhibited growth of a variety of platelet-contaminating bacteria. Therefore,
      supplementation of platelet concentrates with Lcn2 may reduce bacterial
      contamination.

PMID- 24580535
TI  - Defining obesity: second-level agenda setting attributes in black newspapers and
      general audience newspapers.
AB  - This content analysis study examines how obesity is depicted in general-audience
      and Black newspaper stories (N=391) through the lens of second-level agenda
      setting theory. The results reveal that both Black newspapers and general
      audience newspapers generally ascribe individual causes for obesity. While both
      types of newspapers largely neglected to mention solutions for the problem, Black
      newspapers were more likely than general-audience newspapers to suggest both
      individual and societal solutions for treating obesity. For Black newspapers,
      these solutions more often included community interventions. In addition, Black
      newspapers more often used a negative tone in stories and more frequently
      mentioned ethnic and racial minorities as at-risk groups. 

PMID- 24580536
TI  - Successful transplantation of a heart with an atrial septal defect caused by
      blunt trauma.
AB  - We report a case of a successful heart transplantation from a donor after
      multiple trauma. A traumatic atrial septal defect was repaired, and the
      postoperative course was uneventful.

PMID- 24580537
TI  - Physicochemical characteristics, nutritional properties, and health benefits of
      argan oil: a review.
AB  - The argan tree (Argania spinosa L. Skeels), an endemic tree in Morocco, is the
      most remarkable species in North Africa, due to its botanical and bioecologic
      interest as well as its social value. Argan oil is traditionally well known for
      its cardioprotective properties and it is also used in the treatment of skin
      infections. This paper gives an overview of scientific literature available on
      nutritional and pharmacologic properties of argan oil. Owing to its unique
      organoleptic properties associated with its cardioprotective properties, argan
      oil has found, recently, its place in the highly competitive international edible
      oil market. This success is a very positive sign for the preservation of the
      argan tree, the argan forests and, therefore, in general, the biodiversity. 

PMID- 24580538
TI  - Microbiological aspects related to the feasibility of PEF technology for food
      pasteurization.
AB  - Processing unit operations that seek to inactivate harmful microorganisms are of
      primary importance in ascertaining the safety of food. The capability of pulsed
      electric fields (PEF) to inactivate vegetative cells of microorganisms at
      temperatures below those used in thermal processing makes this technology very
      attractive as a nonthermal pasteurization process for the food industry.
      Commercial exploitation of this technology for food pasteurization requires the
      identification of the most PEF-resistant microorganisms that are of concern to
      public health. Then, the treatment conditions applicable at industrial scale that
      would reduce the population of these microorganisms to a level that guarantees
      food safety must be defined. The objective of this paper is to critically compile
      recent, relevant knowledge with the purpose of enhancing the feasibility of using
      PEF technology for food pasteurization and underlining the required research for
      designing PEF pasteurization processes. 

PMID- 24580539
TI  - Specificity of infant digestive conditions: some clues for developing relevant in
      vitro models.
AB  - Digestion of nutrients is an essential function of the newborn infant gut to
      allow growth and development and understanding infant digestive function is
      essential to optimize nutrition and oral drug delivery. Ethical considerations
      prohibit invasive in vivo trials and as a consequence in vitro assays are often
      conducted. However, the choice of in vitro model parameters are not supported by
      an exhaustive analysis of the literature and do not mimic precisely the digestive
      conditions of the infant. This review contains a compilation of the studies which
      characterized the gastroduodenal conditions in full-term or preterm infants of
      variable postnatal age from birth up to six months. Important data about healthy
      full-term infants are reported. The enzymatic (type of enzymes and level of
      activity) and nonenzymatic (milk-based diet, frequency of feeding, bile salt
      concentrations) conditions of digestion in infants are shown to differ
      significantly from those in adults. In addition, the interindividual and
      developmental variability of the digestive conditions in infants is also
      highlighted. 

PMID- 24580540
TI  - Cocoa phytochemicals: recent advances in molecular mechanisms on health.
AB  - Recent reports on cocoa are appealing in that a food commonly consumed for pure
      pleasure might also bring tangible benefits for human health. Cocoa consumption
      is correlated with reduced health risks of cardiovascular diseases, hypertension,
      atherosclerosis, and cancer, and the health-promoting effects of cocoa are
      mediated by cocoa-driven phytochemicals. Cocoa is rich in procyanidins,
      theobromine, (-)-epicatechin, catechins, and caffeine. Among the phytochemicals
      present in consumed cocoa, theobromine is most available in human plasma,
      followed by caffeine, (-)-epicatechin, catechin, and procyanidins. It has been
      reported that cocoa phytochemicals specifically modulate or interact with
      specific molecular targets linked to the pathogenesis of chronic human diseases,
      including cardiovascular diseases, cancer, neurodegenerative diseases, obesity,
      diabetes, and skin aging. This review summarizes comprehensive recent findings on
      the beneficial actions of cocoa-driven phytochemicals in molecular mechanisms of
      human health. 

PMID- 24580541
TI  - Rapid detection of chemical hazards (toxins, dioxins, and PCBs) in seafood.
AB  - Among the various hazards occurring in fish and seafood chemical hazards and in
      particular toxins (ciguatera, scombroid fish poisoning, paralytic shellfish
      poisoning, neurotoxic (brevetoxic) shellfish poisoning, puffer fish poisoning,
      diarrhetic shellfish poisoning) have an important place in food poisoning cases.
      On the other hand, some of the chemical hazards are often due to the pollution of
      the environment (heavy metals, dioxins, polychlorinated biphenyls, and
      halogenated aromatic hydrocarbons) and their detection is neither rapid nor
      facile. As a result there was a great need for developing new rapid and effective
      methods toward the chemical hazards determination mainly because of their high
      toxicity. The aim of this review is to provide the information about the new up
      to-date detection techniques (Immunological, Chemical and Biochemical, and
      Molecular assays) in conjunction with detection limits. The latter is made
      possible by means of inclusion of seven comprehensive and, in most case cases,
      very extended tables. A reference is also made on the risk characterization of
      toxins as regards their importance to food contamination or poisoning. 

PMID- 24580542
TI  - Vapor pressure of water nanodroplets.
AB  - Classical thermodynamics is assumed to be valid up to a certain length-scale,
      below which the discontinuous nature of matter becomes manifest. In particular,
      this must be the case for the description of the vapor pressure based on the
      Kelvin equation. However, the legitimacy of this equation in the nanoscopic
      regime can not be simply established, because the determination of the vapor
      pressure of very small droplets poses a challenge both for experiments and
      simulations. In this article we make use of a grand canonical screening approach
      recently proposed to compute the vapor pressures of finite systems from molecular
      dynamics simulations. This scheme is applied to water droplets, to show that the
      applicability of the Kelvin equation extends to unexpectedly small lengths, of
      only 1 nm, where the inhomogeneities in the density of matter occur within
      spatial lengths of the same order of magnitude as the size of the object. While
      in principle this appears to violate the main assumptions underlying
      thermodynamics, the density profiles reveal, however, that structures of this
      size are still homogeneous in the nanosecond time-scale. Only when the
      inhomogeneity in the density persists through the temporal average, as it is the
      case for clusters of 40 particles or less, do the macroscopic thermodynamics and
      the molecular descriptions depart from each other. 

PMID- 24580546
TI  - The US-based Photomedicine Society.

PMID- 24580547
TI  - The Korean Society for Photomedicine.

PMID- 24580543
TI  - Preferential infiltration of interleukin-4-producing CXCR4+ T cells in the
      lesional muscle but not skin of patients with dermatomyositis.
AB  - Dermatomyositis (DM) and polymyositis (PM) are collectively termed autoimmune
      myopathy. To investigate the difference between muscle- and skin-infiltrating T
      cells and to address their role for myopathy, we characterized T cells that were
      directly expanded from the tissues. Enrolled into this study were 25 patients
      with DM and three patients with PM. Muscle and skin biopsied specimens were
      immersed in cRPMI medium supplemented with interleukin (IL)-2 and anti-CD3/CD28
      antibody-conjugated microbeads. The expanded cells were subjected to flow
      cytometry to examine their phenotypes. We analysed the cytokine concentration in
      the culture supernatants from the expanded T cells and the frequencies of
      cytokine-bearing cells by intracellular staining. There was non-biased in-vitro
      expansion of tissue-infiltrating CD4(+) and CD8(+) T cells from the muscle and
      skin specimens. The majority of expanded T cells were chemokine receptor (CCR)
      type 7(-) CD45RO(+) effecter memory cells with various T cell receptor (TCR)
      Vbetas. The skin-derived but not muscle-derived T cells expressed cutaneous
      lymphocyte antigen (CLA) and CCR10 and secreted large amounts of IL-17A,
      suggesting that T helper type 17 (Th17) cells may have a crucial role in the
      development of skin lesions. Notably, the frequency of IL-4-producing chemokine
      (C-X-C motif) receptor (CXCR)4(+) Th2 cells was significantly higher in the
      muscle-derived cells and correlated inversely with the serum creatine
      phosphokinase (CPK) and lactate dehydrogenase (LDH) levels. stromal-derived
      factor (SDF)-1/CXCL12, a ligand for CXCR4, was expressed at a high level in the
      vascular endothelial cells between muscular fasciculi. Our study suggests that T
      cell populations in the muscle and skin are different, and the Th2 cell
      infiltrate in the muscle is associated with the low severity of myositis in DM. 

PMID- 24580548
TI  - Building awareness of the health risks of sunbed use: identification of target
      groups for prevention.
AB  - PURPOSE: Sunbed use, a recognized risk factor for skin cancer development, is
      common in developed countries. Cost-efficient interventions to reduce the
      negative health consequences of sunbed use are needed. As a first step to
      identify what kind of intervention might be useful, we aimed to assess the
      awareness of potential health risks of sunbed use in current, former, and never
      users as well as in current users with differing risk profiles. METHODS: We
      assessed risk awareness using items addressing the potential health risks of
      sunbed use (e.g. skin damage) in a representative sample of 4851 individuals. The
      response format assessed agreement with each statement. Risk profiles were
      defined by a large number of birthmarks, a history of frequent childhood sunburn,
      or a (family) history of melanoma. RESULTS: Many individuals were not aware of
      potential risks (e.g. agreement to skin cancer risk 72.6%). Current users were
      less aware compared with former and never users [e.g. skin cancer risk (65.6% vs.
      75.9% and 73.0%, respectively; P < 0.001]). Among current users, those with at
      least two risk factors showed the highest proportion of risk aware individuals.
      CONCLUSION: Low risk awareness among current users suggests the need for targeted
      interventions to reduce or discontinue sunbed use.

PMID- 24580549
TI  - A versatile self-assembly strategy for the synthesis of shape-selected colloidal
      noble metal nanoparticle heterodimers.
AB  - The self-assembly of individual nanoparticles into dimers-so-called heterodimers
      is relevant for a broad range of applications, in particular in the vibrant field
      of nanoplasmonics and nanooptics. In this paper we report the synthesis and
      characterization of material- and shape-selected nanoparticle heterodimers
      assembled from individual particles via electrostatic interaction. The
      versatility of the synthetic strategy is shown by assembling combinations of
      metal particles of different shapes, sizes, and metal compositions like a gold
      sphere (90 nm) with either a gold cube (35 nm), gold rhombic dodecahedron (50
      nm), palladium truncated cube (120 nm), palladium rhombic dodecahedron (110 nm),
      palladium octahedron (130 nm), or palladium cubes (25 and 70 nm) as well as a
      silver sphere (90 nm) with palladium cubes (25 and 70 nm). The obtained
      heterodimer combinations are characterized by transmission electron microscopy
      (TEM), scanning electron microscopy (SEM), scanning transmission electron
      microscopy-energy dispersive X-ray spectroscopy (STEM-EDX), dynamic light
      scattering (DLS), and zeta-potential measurements. We describe the optimal
      experimental conditions to achieve the highest yield of heterodimers compared to
      other aggregates. The experimental results have been rationalized using
      theoretical modeling. A proof-of-principle experiment where individual Au-Pd
      heterodimers are exploited for indirect plasmonic sensing of hydrogen finally
      illustrates the potential of these structures to probe catalytic processes at the
      single particle level. 

PMID- 24580550
TI  - miRNA as markers for the diagnostic screening of colon cancer.
AB  - Early screening for colon cancer (CC) allows for early stage diagnosis of the
      malignancy and potentially reduces disease mortality as the cancer is most likely
      curable at its earliest stages. Early detection would be desirable if accurate,
      practical and cost-effective diagnostic measures for this cancer were available.
      Mortality and morbidity from CC represent a major health problem involving a
      malignant disease that is theoretically preventable through screening. Current
      screening methods (e.g., the convenient and inexpensive immunological fecal
      occult blood test, FOBTi, obtained from patients' medical records) either lack
      sensitivity and require dietary restriction, which impedes compliance and use;
      are costly (e.g., colonoscopy), which decreases compliance; or could result in
      mortality. In comparison with the FOBT test, a non-invasive sensitive screen for
      which there is no requirement for dietary restriction would be a more convenient
      test. Colorectal cancer is the only cancer for which colonoscopy is recommended
      as a screening method. Although colonoscopy is a reliable screening tool, the
      invasive nature, abdominal pain, potential complications and high cost have
      hampered the application of this procedure worldwide. A screening approach using
      the stable miRNA molecules, which are relatively non-degradable when extracted
      from non-invasive stool and semi-invasive blood samples by commercially available
      kits and manipulated thereafter, would be preferable to a transcriptomic mRNA-, a
      mutation DNA-, an epigenetic- or a proteomic-based test. The approach uses
      reverse transcriptase, modified real-time quantitative PCR. Although exosomal RNA
      would be missed, using a restricted extraction of total RNA from stool or blood,
      a parallel test could also be carried out on RNA obtained from stool or plasma
      samples, and appropriate corrections for exsosomal loss can be made for accurate
      and quantitative test result. Eventually, a chip can be developed to facilitate
      diagnosis, as has been done for the quantification of genetically modified
      organisms in foods. The gold standard to which the molecular miRNA test is
      compared is colonoscopy, which can be obtained from patients' medical records. If
      performance criteria are met, as detailed herein, a miRNA test in human stool or
      blood samples based on high-throughput automated technologies and quantitative
      expression measurements commonly used in the diagnostic clinical laboratory
      should be advanced to the clinical setting, which will make a significant impact
      on CC prevention. 

PMID- 24580553
TI  - The nature of compounds: a psychocentric perspective.
AB  - Although compound words often seem to be words that themselves contain words,
      this paper argues that this is not the case for the vast majority of lexicalized
      compounds. Rather, it is claimed that as a result of acts of lexical processing,
      the constituents of compound words develop into new lexical representations.
      These representations are bound to specific morphological roles and positions
      (e.g., head, modifier) within a compound word. The development of these
      positionally bound compound constituents creates a rich network of lexical
      knowledge that facilitates compound processing and also creates some of the well
      documented patterns in the psycholinguistic and neurolinguistic study of
      compounding. 

PMID- 24580551
TI  - Prevalence and predictors of PTSD and depression among adolescent victims of the
      Spring 2011 tornado outbreak.
AB  - BACKGROUND: Relatively few studies have examined prevalence and predictors of
      posttraumatic stress disorder (PTSD) or major depressive episode (MDE) in
      disaster-affected adolescents. Fewer still have administered diagnostic measures
      or studied samples exposed to tornadoes, a common type of disaster. Further,
      methodologic problems limit the generalizability of previous findings. This study
      addressed prevalence estimates and risk factors for PTSD and MDE among
      adolescents exposed to the Spring 2011 tornado outbreak in Alabama and Joplin,
      Missouri. METHODS: A large (N = 2000), population-based sample of adolescents and
      caregivers, recruited randomly from tornado-affected communities, participated in
      structured telephone interviews. PTSD and MDE prevalence were estimated for the
      overall sample, by gender, and by age. Hierarchical logistic regression was used
      to identify risk factors for PTSD and MDE. RESULTS: Overall, 6.7% of adolescents
      met diagnostic criteria for PTSD and 7.5% of adolescents met diagnostic criteria
      for MDE since the tornado. Girls were significantly more likely than boys to meet
      diagnostic criteria for MDE, and older adolescents were more likely than younger
      adolescents to report MDE since the tornado. Female gender, prior trauma
      exposure, and an injured family member were associated with greater risk for PTSD
      and MDE. Specific incident characteristics (loss of services, concern about
      others' safety) were associated with greater PTSD risk; prior disaster exposure
      was associated with lower MDE risk. CONCLUSIONS: However, most adolescents were
      resilient following tornado exposure, roughly 1 in 15 developed PTSD, 1 in 13
      developed MDE, and many more endorsed subclinical mental health problems.
      Information regarding specific risk factors can guide early screening,
      prevention, and intervention efforts in disaster-affected communities.

PMID- 24580552
TI  - Effect of hoof orientation and ballast on acceleration and vibration in the hoof
      and distal forelimb following simulated impacts ex vivo.
AB  - REASONS FOR PERFORMING STUDY: We wished to add to the existing baseline data on
      impact loading of the distal limb as a precursor to assessing the potential role
      of impact in injury and joint disease. OBJECTIVES: To examine the effect of 3
      hoof-strike conditions (toe first, flat and heel first) and 2 specimen masses
      (with and without a ballast of ~2% body mass) on impact deceleration and
      vibration frequencies and energies at the hoof, first phalanx and third
      metacarpal. STUDY DESIGN: Biomechanical experiments in cadaver material. METHODS:
      Eight cadaver limbs were subjected to randomised, repeated controlled trials, in
      which the hoof was struck by a pendulum impact-testing machine (impact velocity,
      3.55 m/s) in the 3 strike and 2 mass conditions. Data from triaxial
      accelerometers on the hoof, first phalanx and third metacarpal quantified, for
      all trials, the peak impact acceleration, frequencies in the first 6.4 ms
      following impact, the frequency with the most energy, 95% of the total energy and
      the frequency at 95% cumulative energy. The effects of the strike and mass
      conditions on each variable were statistically tested using repeated-measures
      ANOVA (alpha = 0.05). RESULTS: Signal energy reaching the third metacarpal was 6
      31% of that at the hoof. A heel-first strike produced the largest peak
      accelerations and highest frequencies among all strike conditions, and changing
      the mass had no effect regardless of strike condition. CONCLUSIONS: Large
      accelerations that occur upon impact of the hoof with the ground are attenuated
      by the distal structures of the equine limb, but still carry considerable energy
      within the signal that could be damaging to tissue and are dependent on hoof
      strike condition but not ballast. Our results suggest that impact loading on the
      hoof could be a factor in contributing to bone injury and joint disease in the
      distal limb.

PMID- 24580554
TI  - The information management processes of women living with HPV.
AB  - The human papillomavirus (HPV) represents a significant public health burden
      because of its widespread prevalence, its links to genital warts and cancers, and
      the negative psychosocial impact of HPV infection and diagnosis. Scholars have
      attributed some of these negative effects to insufficient knowledge and
      information about HPV, prompting research on women's HPV information preferences;
      however, little is known about how women obtain, avoid, and use this information.
      To address this lacuna, we designed a study to trace the information management
      processes of women with HPV. Our analysis of interviews with 25 women living with
      HPV revealed a common sequence of emotional, cognitive, and behavioral responses
      to the HPV diagnosis. The authors review these findings and articulate their
      relevance and importance to research, theory, and practice in the discussion. 

PMID- 24580555
TI  - Effects of vegetable consumption on weight loss: a review of the evidence with
      implications for design of randomized controlled trials.
AB  - Vegetable consumption is a key strategy in many weight loss programs but
      establishing the evidence that vegetable consumption per se assists with weight
      loss may be difficult. Creating a dietary energy deficit involves the whole diet,
      so research on the effects of vegetables may need to consider the whole-dietary
      model. The aims of this review were to examine the evidence on whether a higher
      vegetable consumption resulted in greater weight loss in overweight adults
      (compared to lower intakes) in view of a critique study designs with respect to
      their potential impact on outcomes. Using the PubMed search engine, a systematic
      review of randomized controlled trials (RCTs) published in the period 1988 to
      2011 was conducted. Of the 16 RCTs scrutinized, five reported greater weight
      loss, nine no difference, one showed weight gain, and one reported a positive
      association between weight loss and high vegetable consumption. Trials which
      showed beneficial effects compared a healthy high vegetable diet with a control
      diet based on usual consumption patterns, and/or included behavioral support and
      counseling. On face value, the evidence reviewed appeared inconclusive but closer
      examination of study designs exposed important implications for RCTs that examine
      effects of foods on weight loss. 

PMID- 24580557
TI  - Aptamer and its potential applications for food safety.
AB  - Accompanied by industrial globalization, rapid urbanization, and population
      increment, mass production and staple trading for food consumption are upsoaring
      continuously, foodborne disease resulted from various food safety issues is
      currently a crucial public health concern worldwide, which has not only created a
      great burden on both economy and society, but also greatly threatened the
      sustainability of mankind's livelihood and human reproduction. In order to better
      ensure food safety and thus effectively curb the occurrence of foodborne
      diseases, the development and evolving of inspection strategies are indispensable
      measures for quality assurance and conformity assessment. Nowadays, as
      complementary measures to and with advantageous merits over classic analytical
      methods, highly specific and selective aptamer-based assays have found their
      increasingly important roles in various domains of food analysis. This critical
      review summarizes the advantages of aptamer as compared with antibody, introduces
      important evolving variants of systematic evolution of ligands by exponential
      enrichment (SELEX), and presents an overview of potential aptamer applications
      for food safety. 

PMID- 24580556
TI  - Longitudinal changes in lactoferrin concentrations in human milk: a global
      systematic review.
AB  - Lactoferrin is the second most abundant whey protein in human milk and is known
      for its functional benefits, particularly antimicrobial activities. We report a
      comprehensive evaluation of the published literature on quantitative changes in
      lactoferrin in term and preterm human milk through the course of lactation. We
      also considered methods used to quantify lactoferrin. We critically evaluated 94
      articles on human milk with 52 meeting study inclusion criteria (2724 women). A
      descriptive analysis of the data was performed. Lactoferrin concentration was
      highest during early lactation and rapidly declined to remain relatively
      unchanged from 1 month to 2 years of lactation. The unweighted mean of mean (+/
      SEM) concentrations of lactoferrin in early milk (<28 days lactation) was 4.91 +/
      0.31 g/L (range of means 0.34-17.94 g/L; median 4.03). For mature milk, the mean
      of means was 2.10 +/- 0.87 g/L (range of means 0.44-4.4 g/L; median 1.91). The
      majority of data were derived from Europe with fewer studies from Africa and
      South America. There was a paucity of data on preterm milk. This comprehensive
      dataset explains in detail the longitudinal changes of lactoferrin concentrations
      in human milk throughout the world and briefly describes factors that may
      influence these concentrations. 

PMID- 24580558
TI  - Physicochemical characteristics, functional properties, and nutritional benefits
      of peanut oil: a review.
AB  - The legume Arachis hypogaea, commonly known as peanut or groundnut, is a very
      important food crop throughout the tropics and subtropics. Peanut is one of the
      most widely used legumes due to its nutrition and taste, and it occupies a rank
      of major oilseed crop in the world. It has been recognized as a functional food
      due to its role in a health promoting effect. Peanut oil contains a well-balanced
      fatty acid and antioxidant profile that provide protection against harmful
      substances especially free radicals. This paper gives an overview of scientific
      literature available on phytochemical and functional properties of peanut oil.
      Owing to its unique organoleptic properties associated with its cardioprotective
      and anti-inflammatory properties, peanut oil has found, recently, its place on
      the highly competitive international edible oil market. 

PMID- 24580559
TI  - Stress-induced changes in wheat grain composition and quality.
AB  - Abiotic stresses such as drought, salinity, waterlogging, and high temperature
      cause a myriad of changes in the metabolism of plants, and there is a lot of
      overlap in these changes in plants in response to different stresses such as
      drought and salinity. These stress-induced metabolic changes cause impaired crop
      growth thereby resulting in poor yield. The metabolic changes taking place in
      several plant species due to a particular abiotic stress have been revealed from
      the whole plant to the molecular level by researchers, but most studies have
      focused on organs such as leaf, stem, and root. Information on such stress
      induced changes in seed or grains is infrequent in the literature. From the
      information that is available, it is now evident that abiotic stress can induce
      considerable changes in the composition and quality of cereal grains including
      those of wheat, the premier staple food crop in the world. Thus, the present
      review discusses how far different types of stresses, mainly salinity, drought,
      high temperature, and waterlogging, can alter the wheat grain composition and
      quality. By fully uncovering the stress-induced changes in the nutritional values
      of wheat grains it would be possible to establish whether balanced supplies of
      essential nutrients are available to the human population from the wheat crop
      grown on stress-affected areas. 

PMID- 24580560
TI  - Metabolic fate of ellagitannins: implications for health, and research
      perspectives for innovative functional foods.
AB  - Consumption of dietary ellagitannins (ETs) has been associated with different
      health benefits. Nonetheless, ETs are not bioavailable as such and are
      metabolized in vivo. They are partially converted into ellagic acid (EA) in the
      upper gastrointestinal (GI) tract, but this first metabolite is also poorly
      bioavailable. In the lower GI tract, EA and residual ETs are metabolized by gut
      microbiota to produce urolithins, which, together with their conjugate relatives,
      persist at relatively high concentrations in plasma and urine for days after
      ingestion of dietary ETs. Thus, ETs and EA may exert local health benefits on the
      GI tract but systemic health benefits are more likely to result from urolithins.
      Cellular models suggest that, at physiological concentration, urolithins are
      active against chronic degenerative diseases. Health benefits have been proven in
      animal models and during clinical studies. Even so, the crucial involvement of
      gut microbiota in ET bioconversion induces important variability of physiological
      response among humans, giving rise to the concept of high and low urolithin
      producers. This variability among consumers in obtaining potential health
      benefits from dietary ETs raises new challenges for the functional food industry.
      Different research perspectives are discussed to tackle this significant issue
      for nutritionists, food technologists, and consumers. 

PMID- 24580561
TI  - Role of dietary and endogenous antioxidants in diabetes.
AB  - Diabetes affects different people of all ages, race, and sex. This is a condition
      characterized by a state of chronic hyperglycaemia that leads to an increase of
      intracellular oxidative stress linked to the overproduction of free radicals. In
      the present review, we focus our attention on the molecular mechanisms leading to
      oxidative stress-mediates complications with particular regard to central nervous
      system (CNS). Furthermore, the present review reports the effects of different
      kind of antioxidants with enzymatic and nonenzymatic action that may
      significantly decrease the intracellular free radicals' overproduction and
      prevents the hyperglycaemia-mediated complications. 

PMID- 24580562
TI  - A question mark on iron deficiency in 185 million people of Pakistan: its
      outcomes and prevention.
AB  - Micronutrient deficiency especially the iron deficiency is the bane of our lives,
      affecting all strata of society. Unfortunately, the women during pregnancy,
      adolescence, and children are under this curse particularly in developing
      countries like Pakistan. It is one of the biggest reasons of complications during
      pregnancy and malnourished children under five years of age. Maternal death,
      still-births, and underweight births are most common consequences of iron
      deficiency and these outbreaks as iron-deficiency anemia in Pakistan. Disastrous
      nature of iron deficiency requires an urgent call to eradicate it. Hence, the
      solution should not be frail comparing with the huge economic loss and other
      incompatibilities. Flour fortification, supplementation, dietary diversification,
      and especially maternal education are possible solutions for combating this
      micronutrient deficiency. 

PMID- 24580563
TI  - Deviations from plane-wave Mie scattering and precise retrieval of refractive
      index for a single spherical particle in an optical cavity.
AB  - The extinction cross-sections of individual, optically confined aerosol particles
      with radii of a micrometer or less can, in principle, be measured using cavity
      ring-down spectroscopy (CRDS). However, when the particle radius is comparable in
      magnitude to the wavelength of light stored in a high-finesse cavity, the
      phenomenological cross-section retrieved from a CRDS experiment depends on the
      location of the particle in the intracavity standing wave and differs from the
      Mie scattering cross-section for plane-wave irradiation. Using an evaporating
      1,2,6-hexanetriol particle of initial radius ~1.75 MUm confined within the 4.5
      MUm diameter core of a Bessel beam, we demonstrate that the scatter in the
      retrieved extinction efficiency of a single particle is determined by its lateral
      motion, which spans a few wavelengths of the intracavity standing wave used for
      CRDS measurements. Fits of experimental measurements to Mie calculations,
      modified to account for the intracavity standing wave, allow precise retrieval of
      the refractive index of 1,2,6-hexanetriol particles (with relative humidity, RH <
      10%) of 1.47824 +/- 0.00072. 

PMID- 24580564
TI  - ILQINS hexapeptide, identified in lysozyme left-handed helical ribbons and
      nanotubes, forms right-handed helical ribbons and crystals.
AB  - Amyloid fibrils are implicated in over 20 neurodegenerative diseases. The
      mechanisms of fibril structuring and formation are not only of medical and
      biological importance but are also relevant for material science and
      nanotechnologies due to the unique structural and physical properties of
      amyloids. We previously found that hen egg white lysozyme, homologous to the
      disease-related human lysozyme, can form left-handed giant ribbons, closing into
      nanotubes. By using matrix-assisted laser desorption ionization mass spectrometry
      analysis, we here identify a key component of such structures: the ILQINS
      hexapeptide. By combining atomic force microscopy and circular dichorism, we find
      that this fragment, synthesized by solid-phase peptide synthesis, also forms
      fibrillar structures in water at pH 2. However, all fibrillar structures formed
      possess an unexpected right-handed twist, a rare chirality within the corpus of
      amyloid experimental observations. We confirm by small- and wide-angle X-ray
      scattering and molecular dynamics simulations that these fibrils are composed of
      conventional left-handed beta-sheets, but that packing stresses between adjacent
      sheets create this twist of unusual handedness. We also show that the right
      handed fibrils represent a metastable state toward beta-sheet-based microcrystals
      formation. 

PMID- 24580566
TI  - Targeting quadriceps inhibition with electromyographic biofeedback: a
      neuroplastic approach.
AB  - Weakness of the quadriceps is a common occurrence in patients after knee injury
      or surgery; this weakness is due to a natural mechanism known as arthrogenic
      muscle inhibition. If inhibition of the quadriceps persists, it can become
      detrimental to a patient's function and lead to additional pathologies. A number
      of therapeutic interventions have be used in the rehabilitation of these
      patients, but few have proven to be successful. Electromyographic biofeedback is
      one modality that has demonstrated positive outcomes in patients by restoring
      quadriceps function. However, the reason for the effectiveness of this modality
      has yet to be fully explained in the area of rehabilitation. Neuroplasticity is a
      phenomenon that has gained much attention in rehabilitation, and its potential
      continues to grow. After an injury, the brain has the ability to enhance recovery
      by strengthening its neural circuitry. Through rehabilitation, clinicians can use
      attentional strategies to foster neuroplasticity and promote the recovery of
      their patients. In this article we provide reasoning for the effectiveness of
      electromyographic biofeedback using the evidence of neuroplasticity. With this
      information, we hope to provide clinicians a rationale for using this tool in the
      rehabilitation of patients with persistent quadriceps inhibition. 

PMID- 24580568
TI  - Functional electrical stimulation on improving foot drop gait in poststroke
      rehabilitation: a review of its technology and clinical efficacy.
AB  - This article presents technical developments in and clinical applications of
      functional electrical stimulation (FES) in the recovery of gait and motor
      function in poststroke rehabilitation. We review stroke incidence, stimulator
      design, brain-computer interface-based FES systems, and clinical applications of
      FES. Developments in different types of foot drop stimulators are reviewed,
      including hard-wired and microprocessor-based surface stimulator systems. The
      replacement of the foot switch by using artificial and "natural" sensors as the
      primary control in foot drop stimulators is reviewed. In addition, this review
      evaluates the clinical effects of FES applications in gait, motor control, and
      functional ability compared to conventional therapy alone during poststroke
      rehabilitation. The literature suggests the combination of FES and a conventional
      rehabilitation program has a positive therapeutic effect on the recovery of gait,
      motor function, energy expenditure, and functional ability in stroke patients. On
      the basis of our review, we recommend using FES therapy along with a conventional
      rehabilitation program in the poststroke rehabilitation process. In summary, this
      article describes the need for rigorous technological development, clinical
      studies, and collaboration between clinicians and engineers for FES systems.
      Future research would facilitate the design of costeffective FES systems as well
      as analysis of FES applications in stroke patients to optimize the rehabilitation
      process. 

PMID- 24580567
TI  - Heart rate variability in type 2 diabetes mellitus.
AB  - Heart rate variability (HRV) is a noninvasive measure of cardiac autonomic
      modulation. Time and frequency domain measures have primarily been examined in
      patients with type 2 diabetes mellitus (T2D). Not only do frequency domain HRV
      parameters tend to be reduced in T2D, but healthy individuals with low HRV are
      also more likely to develop T2D. Furthermore, patients with T2D with low HRV have
      an increased prevalence of complications and risk of mortality compared with
      those with normal autonomic function. These findings provide support for the use
      of HRV as a risk indicator in T2D. Exercise is considered an important component
      to T2D prevention and treatment strategies. To date, few studies have examined
      the changes in HRV with exercise in T2D. One study showed changes in resting HRV,
      two studies showed changes in HRV during or following acute stressors, and one
      study showed no changes in HRV but improvements in baroreflex sensitivity. The
      most pronounced changes in HRV were realized following the exercise intervention
      with the greatest frequency of supervised exercise sessions and with the greatest
      intensity and duration of exercise bouts. These findings suggest that exercise
      following current American College of Sports Medicine/American Diabetes
      Association guidelines may be important in the prevention and treatment of T2D to
      improve autonomic function and reduce the risk of complications and mortality. 

PMID- 24580569
TI  - Design, control, and sensory feedback of externally powered hand prostheses: a
      literature review.
AB  - In recent years, there has been a steep rise in the quality of prostheses for
      patients with upper limb amputations. Researchers have begun to identify methods
      of making prosthetic hands both functional and cosmetically appealing, in
      contrast to past designs. Many improvements have occurred because of novel design
      strategies, such as the use of underactuated mechanisms, which allow for more
      degrees of freedom (DOF) or help reduce the weight of the prosthesis. The
      increase in functionality is also due in large part to advancements in control
      strategies for prosthetic hands. One common control method, using
      electromyographic (EMG) signals generated by muscle contractions, has allowed for
      an increase in the DOF of hand designs and a larger number of available grip
      patterns with little added complexity for the wearer. Another recent improvement
      in prosthetic hand design instead employs electroneurographic (ENG) signals,
      requiring an interface directly with the peripheral nervous system (PNS) or the
      central nervous system (CNS). Despite the recent progress in design and control
      strategies, however, prosthetic hands are still far more limited than the actual
      human hand. This review outlines the recent progress in the development of
      electrode-based prosthetic hands, detailing advancements in the areas of design,
      sensory feedback, and control through EMG and ENG signals (with a particular
      focus on interfaces with the PNS). The potential benefits and limitations of both
      control strategies, in terms of signal classification, invasiveness, and sensory
      feedback, are discussed. Finally, a brief overview of interfaces with the CNS is
      provided, and potential future developments for prosthetic hand design are
      discussed. 

PMID- 24580571
TI  - Poly-victimization and executive functions in junior college students.
AB  - This study sought to characterize executive dysfunctions in poly-victimized
      students without posttraumatic stress disorder (PTSD) symptoms and the
      relationship between neuropsychological and behavioral rating measures of
      executive functions (EFs). Based on self-report data of exposure to victimization
      and PTSD symptoms, 259 junior college students aged 18-21 years were classified
      into four groups: poly-victimization with PTSD symptoms (PVP), poly-victimization
      without PTSD symptoms (PVnP), non-poly-victimization (nPV), and non-victimization
      (nV). Respondents also completed the Behavior Rating Inventory of Executive
      Function-Adult Version (BRIEF-A). Of the 259 participants, 131 were administered
      a battery of neuropsychological tests from the Cambridge Neuropsychological
      Testing Automated Battery (CANTAB). The PVP group and the PVnP group performed
      worse than the nV group on most BRIEF-A scales. When compared with the nPV group,
      the PVP group demonstrated poorer performance on the scales of Inhibit, Shift,
      Emotional Control, Initiate, and Working Memory, while the PVnP group performed
      more poorly on the Working Memory scale and the Task Monitor scale. For all BRIEF
      A scales, no significant differences were detected between the PVP group and the
      PVnP group. This study showed no between-group differences for most of the
      neuropsychological tests except for the Stop Signal Task (SST), and no
      correlations between these two measures of EFs. Overall, we found evidence of an
      association between deficits in EFs and poly-victimization. Although our study
      raises questions about the relationship between these two measures of EFs, it
      suggests that the use of the BRIEF-A in conjunction with the CANTAB provides a
      more complete assessment of the executive dysfunctions. 

PMID- 24580570
TI  - Treatment effectiveness of PMTO for children's behavior problems in Iceland:
      assessing parenting practices in a randomized controlled trial.
AB  - Findings are presented from an Icelandic randomized control trial (RCT)
      evaluating parent management training - Oregon model (PMTOTM), a parent training
      intervention designed to improve parenting practices and reduce child behavior
      problems. In a prior report from this effectiveness study that focused on child
      outcomes, children in the PMTO condition showed greater reductions in reported
      child adjustment problems relative to the comparison group. The present report
      focuses on observed parenting practices as the targeted outcome, with risk by
      treatment moderators also tested. It was hypothesized that mothers assigned to
      the PMTO condition would show greater gains in pre-post parenting practices
      relative to controls. The sample was recruited from five municipalities
      throughout Iceland and included 102 participating families of children with
      behavior problems. Cases were referred by community professionals and randomly
      assigned to either PMTO (n = 51) or community services usually offered (n = 51).
      Child age ranged from 5 to 12 years; 73% were boys. Contrary to expectations,
      findings showed no main effects for changes in maternal parenting. However,
      evaluation of risk by treatment moderators showed greater gains in parenting
      practices for mothers who increased in depressed mood within the PMTO group
      relative to their counterparts in the comparison group. This finding suggests
      that PMTO prevented the expected damaging effects of depression on maternal
      parenting. Failure to find hypothesized main effects may indicate that there were
      some unobserved factors regarding the measurement and a need to further adapt the
      global observational procedures to Icelandic culture. 

PMID- 24580572
TI  - Ethosomes: versatile vesicular carriers for efficient transdermal delivery of
      therapeutic agents.
AB  - Delivery across skin is attractive due to its easy accessibility. However, drug
      delivery across skin is still a challenge in biomedical sciences. Over the past
      few decades, various successful novel devices and techniques have emerged to
      optimize drug delivery across skin whose obstructing behavior constricts entry of
      most of the therapeutic agents. Inability of various conventional vesicular
      formulations, e.g. liposomes to pass through the tapered (>30 nm) intercellular
      channels of stratum corneum, rendered invention of some lipid based vesicular
      carrier systems such as ethosomes which consist of phospholipid, ethanol and
      water. Ethosomes are non-invasive delivery carriers that enable drugs to reach
      the deep skin layers and/or the systemic circulation. In spite of their
      sophistication in conceptuality, they are exemplified by easiness in their
      preparation, safety and efficacy - a combination that can highly inflate their
      application. This review attempts to describe all aspects of ethosomes including
      roles and upshots of different excipients, various methods of preparation and
      characterizations, research reports on various drug deliveries, patent reports
      and future prospects.

PMID- 24580574
TI  - Noise and disturbance in quantum measurements: an information-theoretic approach.
AB  - We introduce information-theoretic definitions for noise and disturbance in
      quantum measurements and prove a state-independent noise-disturbance tradeoff
      relation that these quantities have to satisfy in any conceivable setup. Contrary
      to previous approaches, the information-theoretic quantities we define are
      invariant under the relabelling of outcomes and allow for the possibility of
      using quantum or classical operations to "correct" for the disturbance. We also
      show how our bound implies strong tradeoff relations for mean square deviations. 

PMID- 24580575
TI  - Effective mass signatures in multiphoton pair production.
AB  - Electron-positron pair production in oscillating electric fields is investigated
      in the nonperturbative threshold regime. Accurate numerical solutions of quantum
      kinetic theory for corresponding observables are presented and analyzed in terms
      of a proposed model for an effective mass of electrons and positrons acquired
      within the given strong electric field. Although this effective mass cannot
      provide an exact description of the collective interaction of a charged particle
      with the strong field, physical observables are identified which carry direct and
      sensitive signatures of the effective mass. 

PMID- 24580576
TI  - Cavity cooling of an ensemble spin system.
AB  - We describe how sideband cooling techniques may be applied to large spin
      ensembles in magnetic resonance. Using the Tavis-Cummings model in the presence
      of a Rabi drive, we solve a Markovian master equation describing the joint spin
      cavity dynamics to derive cooling rates as a function of ensemble size. Our
      calculations indicate that the coupled angular momentum subspaces of a spin
      ensemble containing roughly 10(11) electron spins may be polarized in a time many
      orders of magnitude shorter than the typical thermal relaxation time. The
      described techniques should permit efficient removal of entropy for spin-based
      quantum information processors and fast polarization of spin samples. The
      proposed application of a standard technique in quantum optics to magnetic
      resonance also serves to reinforce the connection between the two fields, which
      has recently begun to be explored in further detail due to the development of
      hybrid designs for manufacturing noise-resilient quantum devices.

PMID- 24580565
TI  - Manipulating the microvasculature and its microenvironment.
AB  - The microvasculature is a dynamic cellular system necessary for tissue health and
      function. Therapeutic strategies that target the microvasculature are expanding
      and evolving, including those promoting angiogenesis and microvascular expansion.
      When considering how to manipulate angiogenesis, either as part of a tissue
      construction approach or a therapy to improve tissue blood flow, it is important
      to know the microenvironmental factors that regulate and direct neovessel
      sprouting and growth. Much is known concerning both diffusible and matrix-bound
      angiogenic factors, which stimulate and guide angiogenic activity. How the other
      aspects of the extravascular microenvironment, including tissue biomechanics and
      structure, influence new vessel formation is less well known. Recent research,
      however, is providing new insights into these mechanisms and demonstrating that
      the extent and character of angiogenesis (and the resulting new microcirculation)
      is significantly affected. These observations and the resulting implications with
      respect to tissue construction and microvascular therapy are addressed. 

PMID- 24580573
TI  - Thiol-based redox proteins in abscisic acid and methyl jasmonate signaling in
      Brassica napus guard cells.
AB  - Reversibly oxidized cysteine sulfhydryl groups serve as redox sensors or targets
      of redox sensing that are important in various physiological processes. However,
      little is known about redox-sensitive proteins in guard cells and how they
      function in stomatal signaling. In this study, Brassica napus guard-cell proteins
      altered by redox in response to abscisic acid (ABA) or methyl jasmonate (MeJA)
      were identified by complementary proteomics approaches, saturation differential
      in-gel electrophoresis and isotope-coded affinity tagging. In total, 65 and 118
      potential redox-responsive proteins were identified in ABA- and MeJA-treated
      guard cells, respectively. All the proteins contain at least one cysteine, and
      over half of them are predicted to form intra-molecular disulfide bonds. Most of
      the proteins fall into the functional groups of 'energy', 'stress and defense'
      and 'metabolism'. Based on the peptide sequences identified by mass spectrometry,
      30 proteins were common to ABA- and MeJA-treated samples. A total of 44 cysteines
      were mapped in the identified proteins, and their levels of redox sensitivity
      were quantified. Two of the proteins, a sucrose non-fermenting 1-related protein
      kinase and an isopropylmalate dehydrogenase, were confirmed to be redox-regulated
      and involved in stomatal movement. This study creates an inventory of potential
      redox switches, and highlights a protein redox regulatory mechanism in ABA and
      MeJA signal transduction in guard cells. 

PMID- 24580577
TI  - Protected quantum computing: interleaving gate operations with dynamical
      decoupling sequences.
AB  - Implementing precise operations on quantum systems is one of the biggest
      challenges for building quantum devices in a noisy environment. Dynamical
      decoupling attenuates the destructive effect of the environmental noise, but so
      far, it has been used primarily in the context of quantum memories. Here, we
      experimentally demonstrate a general scheme for combining dynamical decoupling
      with quantum logical gate operations using the example of an electron-spin qubit
      of a single nitrogen-vacancy center in diamond. We achieve process fidelities
      >98% for gate times that are 2 orders of magnitude longer than the unprotected
      dephasing time T2. 

PMID- 24580579
TI  - Scalable implementation of boson sampling with trapped ions.
AB  - Boson sampling solves a classically intractable problem by sampling from a
      probability distribution given by matrix permanents. We propose a scalable
      implementation of boson sampling using local transverse phonon modes of trapped
      ions to encode the bosons. The proposed scheme allows deterministic preparation
      and high-efficiency readout of the bosons in the Fock states and universal mode
      mixing. With the state-of-the-art trapped ion technology, it is feasible to
      realize boson sampling with tens of bosons by this scheme, which would outperform
      the most powerful classical computers and constitute an effective disproof of the
      famous extended Church-Turing thesis. 

PMID- 24580578
TI  - Implementation of dynamically corrected gates on a single electron spin in
      diamond.
AB  - Precise control of an open quantum system is critical to quantum information
      processing but is challenging due to inevitable interactions between the quantum
      system and the environment. We demonstrated experimentally a type of dynamically
      corrected gates using only bounded-strength pulses on the nitrogen-vacancy
      centers in diamond. The infidelity of quantum gates caused by a nuclear-spin bath
      is reduced from being the second order to the sixth order of the noise-to-control
      field ratio, which offers greater efficiency in reducing infidelity. The quantum
      gates have been protected to the limit essentially set by the spin-lattice
      relaxation time T1. Our work marks an important step towards fault-tolerant
      quantum computation in realistic systems. 

PMID- 24580580
TI  - No-pumping theorem for many particle stochastic pumps.
AB  - Stochastic pumps are models of artificial molecular machines which are driven by
      periodic time variation of parameters, such as site and barrier energies. The no
      pumping theorem states that no directed motion is generated by variation of only
      site or barrier energies [S. Rahav, J. Horowitz, and C. Jarzynski, Phys. Rev.
      Lett. 101, 140602 (2008)]. We study stochastic pumps of several interacting
      particles and demonstrate that the net current of particles satisfies an
      additional no-pumping theorem.

PMID- 24580581
TI  - Explore or exploit? A generic model and an exactly solvable case.
AB  - Finding a good compromise between the exploitation of known resources and the
      exploration of unknown, but potentially more profitable choices, is a general
      problem, which arises in many different scientific disciplines. We propose a
      stylized model for these exploration-exploitation situations, including
      population or economic growth, portfolio optimization, evolutionary dynamics, or
      the problem of optimal pinning of vortices or dislocations in disordered
      materials. We find the exact growth rate of this model for treelike geometries
      and prove the existence of an optimal migration rate in this case. Numerical
      simulations in the one-dimensional case confirm the generic existence of an
      optimum. 

PMID- 24580582
TI  - Spatiotemporally complete condensation in a non-Poissonian exclusion process.
AB  - We investigate a non-Poissonian version of the asymmetric simple exclusion
      process, motivated by the observation that coarse graining the interactions
      between particles in complex systems generically leads to a stochastic process
      with a non-Markovian (history-dependent) character. We characterize a large
      family of one-dimensional hopping processes using a waiting-time distribution for
      individual particle hops. We find that when its variance is infinite, a real
      space condensate forms that is complete in space (involves all particles) and
      time (exists at almost any given instant) in the thermodynamic limit. The
      mechanism for the onset and stability of the condensate is rather subtle and
      depends on the microscopic dynamics subsequent to a failed particle hop attempt. 

PMID- 24580583
TI  - High-accuracy measurement of the blackbody radiation frequency shift of the
      ground-state hyperfine transition in 133Cs.
AB  - We report a high-accuracy direct measurement of the blackbody radiation shift of
      the 133Cs ground-state hyperfine transition. This frequency shift is one of the
      largest systematic frequency biases encountered in realizing the current
      definition of the International System of Units (SI) second. Uncertainty in the
      blackbody radiation frequency shift correction has led to its being the focus of
      intense theoretical effort by a variety of research groups. Our experimental
      measurement of the shift used three primary frequency standards operating at
      different temperatures. We achieved an uncertainty a factor of five smaller than
      the previous best direct measurement. These results tend to validate the claimed
      accuracy of the recently calculated values.

PMID- 24580584
TI  - Black hole interior in the holographic correspondence and the information
      paradox.
AB  - We show that, within the AdS/CFT correspondence, recent formulations of the
      information paradox can be reduced to a question about the existence of certain
      kinds of operators in the conformal field theory (CFT). We describe a remarkably
      simple construction of these operators on a given state of the CFT. Our
      construction leads to a smooth horizon, addresses the strong subadditivity
      paradox, while preserving locality within effective field theory, and reconciles
      the existence of the interior with the growth of states with energy in the CFT.
      We also extend our construction to nonequilibrium states. 

PMID- 24580585
TI  - Neutrinos help reconcile Planck measurements with the local universe.
AB  - Current measurements of the low and high redshift Universe are in tension if we
      restrict ourselves to the standard six-parameter model of flat LambdaCDM. This
      tension has two parts. First, the Planck satellite data suggest a higher
      normalization of matter perturbations than local measurements of galaxy clusters.
      Second, the expansion rate of the Universe today, H0, derived from local distance
      redshift measurements is significantly higher than that inferred using the
      acoustic scale in galaxy surveys and the Planck data as a standard ruler. The
      addition of a sterile neutrino species changes the acoustic scale and brings the
      two into agreement; meanwhile, adding mass to the active neutrinos or to a
      sterile neutrino can suppress the growth of structure, bringing the cluster data
      into better concordance as well. For our fiducial data set combination, with
      statistical errors for clusters, a model with a massive sterile neutrino shows
      3.5sigma evidence for a nonzero mass and an even stronger rejection of the
      minimal model. A model with massive active neutrinos and a massless sterile
      neutrino is similarly preferred. An eV-scale sterile neutrino mass--of interest
      for short baseline and reactor anomalies--is well within the allowed range. We
      caution that (i) unknown astrophysical systematic errors in any of the data sets
      could weaken this conclusion, but they would need to be several times the known
      errors to eliminate the tensions entirely; (ii) the results we find are at some
      variance with analyses that do not include cluster measurements; and (iii) some
      tension remains among the data sets even when new neutrino physics is included.

PMID- 24580586
TI  - Evidence for massive neutrinos from cosmic microwave background and lensing
      observations.
AB  - We discuss whether massive neutrinos (either active or sterile) can reconcile
      some of the tensions within cosmological data that have been brought into focus
      by the recently released Planck data. We point out that a discrepancy is present
      when comparing the primary CMB and lensing measurements both from the CMB and
      galaxy lensing data using CFHTLenS, similar to that which arises when comparing
      CMB measurements and SZ cluster counts. A consistent picture emerges and
      including a prior for the cluster constraints and BAOs we find that for an active
      neutrino model with three degenerate neutrinos, ?m(nu)=(0.320+/-0.081)  eV,
      whereas for a sterile neutrino, in addition to 3 neutrinos with a standard
      hierarchy and ?m(nu)=0.06  eV, m(nu,sterile)(eff)=(0.450+/-0.124)  eV and
      DeltaN(eff)=0.45+/-0.23. In both cases there is a significant detection of
      modification to the neutrino sector from the standard model and in the case of
      the sterile neutrino it is possible to reconcile the BAO and local H0
      measurements. However, a caveat to our result is some internal tension between
      the CMB and lensing and cluster observations, and the masses are in excess of
      those estimated from the shape of the matter power spectrum from galaxy surveys.

PMID- 24580587
TI  - Integrable deformation of the AdS5*S5 superstring action.
AB  - An integrable deformation of the type IIB AdS5*S5 superstring action is
      presented. The deformed field equations, Lax connection, and kappa-symmetry
      transformations are given. The original psu(2,2|4) symmetry is expected to become
      q deformed. 

PMID- 24580589
TI  - Ultrafast Stark-induced polaritonic switches.
AB  - A laser pulse, several meV red detuned from the excitonic line of a quantum well,
      has been shown to induce an almost instantaneous and rigid shift of the lower and
      upper polariton branches. Here we demonstrate that through this shift ultrafast
      all-optical control of the polariton population in a semiconductor microcavity
      should be achievable. In the proposed setup, a Stark field is used to bring the
      lower polariton branch in or out of resonance with a quasiresonant continuous
      wave laser, thereby favoring or inhibiting the injection of polaritons into the
      cavity. Moreover, we show that this technique allows for the implementation of
      optical switches with extremely high repetition rates. 

PMID- 24580590
TI  - Ancilla-assisted measurement of photonic spatial correlations and entanglement.
AB  - We report an experiment in which the moments of spatial coordinates are measured
      in down-converted photons directly, without having to reconstruct any marginal
      probability distributions. We use a spatial light modulator to couple the spatial
      degrees of freedom and the polarization of the fields, which acts as an ancilla
      system. Information about the spatial correlations is obtained via measurements
      on the ancilla qubit. Among other applications, this new method provides a more
      efficient technique to identify continuous variable entanglement. 

PMID- 24580588
TI  - Candidates for twin chiral bands in 102Rh.
AB  - Excited states in 102Rh, populated in the fusion-evaporation reaction
      Zr94(11B,3n)102Rh at a beam energy of 36 MeV, were studied using the Indian
      National Gamma Array spectrometer at Inter University Accelerator Center, New
      Delhi. The angular correlations and the electromagnetic character of some of the
      gamma-ray transitions observed were investigated in detail. A new chiral
      candidate sister band was found. Lifetimes of exited states in both chiral
      candidate bands of 102Rh were measured for the first time in the A~100 mass
      region by means of the Doppler-shift attenuation technique. The derived reduced
      transition probabilities are compared to the predictions of the two
      quasiparticles plus triaxial rotor model. Both experimental results and
      calculations do not support the presence of static chirality in 102Rh.

PMID- 24580591
TI  - Dislocation parity effects in crystals with quadratic nonlinear response.
AB  - The effect of edge topological dislocations on the phase matching spectrum of
      quadratic nonlinear photonic crystals was studied theoretically and
      experimentally. We have found that the parity of the dislocation's topological
      charge governs the transfer of energy between an input wave and its second
      harmonic. A dislocation with an odd topological charge nulls the efficiency of
      the otherwise optimal phase matched wavelength, whereas high conversion is now
      achieved at new wavelengths that exhibited low efficiency without the
      dislocation. However, when the topological charge is an even number, the
      dislocation has a negligible effect on the efficiency curve. This effect is
      observed in periodically poled crystals having a single peak in the phase
      matching spectrum, as well as in phase-reversed and quasiperiodic nonlinear
      photonic crystals that are characterized by multiple efficiency peaks, where a
      dimple is imprinted on each spectral peak. 

PMID- 24580592
TI  - Electromagnetically induced torque on a large ring in the microwave range.
AB  - We report on the exchange of orbital angular momentum between an electromagnetic
      wave and a 30 cm diameter ring. Using a turnstile antenna in the GHz range, we
      induce a torque on a suspended copper strip of the order of 10(-8)  N m.
      Rotations of a few degrees and accelerations up to 4*10(-4)  degrees /s2 are
      observed. A linear dependence of the acceleration as a function of the applied
      power is found. There are many applications in the detection of angular momentum
      in electromagnetics, in acoustics, and also in the magnetization of
      nanostructures.

PMID- 24580593
TI  - High-resolution multislice x-ray ptychography of extended thick objects.
AB  - We report the first demonstration of hard x-ray ptychography using a multislice
      approach, which can solve the problem of the limited spatial resolution under the
      projection approximation. We measured ptychographic diffraction patterns of a two
      layered object with a 105  MUm gap using 7 keV focused coherent x rays. We
      successfully reconstructed the phase map of each layer at ~50  nm resolution
      using a multislice approach, while the resolution was worse than ~192  nm under
      the projection approximation. The present method has the potential to enable the
      three-dimensional high-resolution observation of extended thick specimens in
      materials science and biology. 

PMID- 24580594
TI  - Optically induced indirect photonic transitions in a slow light photonic crystal
      waveguide.
AB  - We demonstrate indirect photonic transitions in a silicon slow light photonic
      crystal waveguide. The transitions are driven by an optically generated
      refractive index front that moves along the waveguide and interacts with a signal
      pulse copropagating in the structure. We experimentally confirm a theoretical
      model which indicates that the ratio of the frequency and wave vector shifts
      associated with the indirect photonic transition is identical to the propagation
      velocity of the refractive index front. The physical origin of the transitions
      achieved here is fundamentally different than in previously proposed refractive
      index modulation concepts with fixed temporal and spatial modulation frequencies;
      as here, the interaction with the refractive index front results in a Doppler
      like signal frequency and wave vector shift. Consequently, the bandwidth over
      which perfect mode frequency and wave vector matching is achieved is not
      intrinsically limited by the shape of the photonic bands, and tuning of the
      indirect photonic transitions is possible without any need for geometrical
      modifications of the structure. Our device is genuinely nonreciprocal, as it
      provides different frequency shifts for co- and counterpropagating signal and
      index fronts. 

PMID- 24580595
TI  - Background-free stimulated Raman spectroscopy and microscopy.
AB  - We propose a three-color, double-modulation scheme for the background-free
      detection of stimulated Raman scattering (SRS). We call the scheme stimulated
      Raman gain and opposite loss detection (SRGOLD). It exploits the symmetric nature
      of potential parasitic signals (cross phase modulation, two-photon absorption,
      and thermal effects) to the end of suppressing them. Conversely, the
      antisymmetric nature of SRS provides for a twofold increase in the magnitude of
      the SRS signal. We experimentally demonstrate SRGOLD spectroscopy and microscopy
      on test samples as well as on mice skin samples. 

PMID- 24580596
TI  - Continuous transition between two limits of spiral wave dynamics in an excitable
      medium.
AB  - By application of a free-boundary approach, we prove the existence of a
      continuous transition and a full spectrum of solutions between the two known
      limits of spiral wave dynamics. We identify a control parameter whose essential
      importance was not realized in earlier studies of spatiotemporal pattern
      selection in excitable media. The predictions of the free-boundary approach are
      in good quantitative agreement with results from numerical reaction-diffusion
      simulations performed on the modified Barkley model. 

PMID- 24580597
TI  - Controlling unstable chaos: stabilizing chimera states by feedback.
AB  - We present a control scheme that is able to find and stabilize an unstable
      chaotic regime in a system with a large number of interacting particles. This
      allows us to track a high dimensional chaotic attractor through a bifurcation
      where it loses its attractivity. Similar to classical delayed feedback control,
      the scheme is noninvasive, however only in an appropriately relaxed sense
      considering the chaotic regime as a statistical equilibrium displaying random
      fluctuations as a finite size effect. We demonstrate the control scheme for so
      called chimera states, which are coherence-incoherence patterns in coupled
      oscillator systems. The control makes chimera states observable close to
      coherence, for small numbers of oscillators, and for random initial conditions. 

PMID- 24580598
TI  - Wave systems with an infinite number of localized traveling waves.
AB  - In many wave systems, propagation of steadily traveling solitons or kinks is
      prohibited because of resonances with linear excitations. We show that wave
      systems with resonances may admit an infinite number of traveling solitons or
      kinks if the closest to the real axis singularities of a limiting asymptotic
      solution in the complex upper half plane are of the form z+/-=+/-alpha+ibeta,
      alpha?0. This quite general statement is illustrated by examples of the fifth
      order Korteweg-de Vries equation, the discrete cubic-quintic Klein-Gordon
      equation, and the nonlocal double sine-Gordon equations. 

PMID- 24580599
TI  - Ultrathin three-dimensional thermal cloak.
AB  - We report the first experimental realization of a three-dimensional thermal cloak
      shielding an air bubble in a bulk metal without disturbing the external
      conductive thermal flux. The cloak is made of a thin layer of homogeneous and
      isotropic material with specially designed three-dimensional manufacturing. The
      cloak's thickness is 100  MUm while the cloaked air bubble has a diameter of 1
      cm, achieving the ratio between dimensions of the cloak and the cloaked object 2
      orders smaller than previous thermal cloaks, which were mainly realized in a two
      dimensional geometry. This work can find applications in novel thermal devices in
      the three-dimensional physical space. 

PMID- 24580600
TI  - Experimental demonstration of a bilayer thermal cloak.
AB  - Invisibility has attracted intensive research in various communities, e.g.,
      optics, electromagnetics, acoustics, thermodynamics, dc, etc. However, many
      experimental demonstrations have only been achieved by virtue of simplified
      approaches due to the inhomogeneous and extreme parameters imposed by the
      transformation-optic method, and usually require a challenging realization with
      metamaterials. In this Letter, we demonstrate a bilayer thermal cloak made of
      bulk isotropic materials, and it has been validated as an exact cloak. We
      experimentally verified its ability to maintain the heat front and its heat
      protection capabilities in a 2D proof-of-concept experiment. The robustness of
      this scheme is validated in both 2D (including oblique heat front incidence) and
      3D configurations. The proposed scheme may open a new avenue to control the
      diffusive heat flow in ways inconceivable with phonons, and also inspire new
      alternatives to the functionalities promised by transformation optics. 

PMID- 24580601
TI  - Crossover of varicose and whipping instabilities in electrified microjets.
AB  - In electrified liquid jets, varicose instability leads to jet breakup into
      droplets while whipping instability is responsible for jet stretching. We show
      that the coupling and relative importance of these two instabilities dictates the
      outcome for jet breakup. The codevelopment of transverse and radial perturbations
      lead to remarkable breakup modes linked to initial perturbation magnitude,
      perturbation wave numbers, and jet charge levels. 

PMID- 24580602
TI  - Enhanced Cherenkov-wake amplification by an active medium.
AB  - A Cherenkov wake confined by perfectly reflecting transverse walls is amplified
      if the dielectric medium is active. Because of the multiple-reflections process,
      the effective gain of the wake is enhanced compared to a ray propagating in a
      straight line. Higher enhancement occurs when the electron velocity is close to
      the Cherenkov velocity. This Cherenkov wake can then accelerate a second bunch of
      electrons trailing the first. Gradients larger than 1 GV/m are predicted before
      saturation becomes a major impediment. 

PMID- 24580603
TI  - High-adiabat high-foot inertial confinement fusion implosion experiments on the
      national ignition facility.
AB  - This Letter reports on a series of high-adiabat implosions of cryogenic layered
      deuterium-tritium (DT) capsules indirectly driven by a "high-foot" laser drive
      pulse at the National Ignition Facility. High-foot implosions have high ablation
      velocities and large density gradient scale lengths and are more resistant to
      ablation-front Rayleigh-Taylor instability induced mixing of ablator material
      into the DT hot spot. Indeed, the observed hot spot mix in these implosions was
      low and the measured neutron yields were typically 50% (or higher) of the yields
      predicted by simulation. On one high performing shot (N130812), 1.7 MJ of laser
      energy at a peak power of 350 TW was used to obtain a peak hohlraum radiation
      temperature of ~300  eV. The resulting experimental neutron yield was (2.4+/
      0.05)*10(15) DT, the fuel rhoR was (0.86+/-0.063)  g/cm2, and the measured Tion
      was (4.2+/-0.16)  keV, corresponding to 8 kJ of fusion yield, with ~1/3 of the
      yield caused by self-heating of the fuel by alpha particles emitted in the
      initial reactions. The generalized Lawson criteria, an ignition metric, was 0.43
      and the neutron yield was ~70% of the value predicted by simulations that include
      alpha-particle self-heating.

PMID- 24580604
TI  - Design of a high-foot high-adiabat ICF capsule for the national ignition
      facility.
AB  - The National Ignition Campaign's [M. J. Edwards et al., Phys. Plasmas 20, 070501
      (2013)] point design implosion has achieved DT neutron yields of 7.5*10(14)
      neutrons, inferred stagnation pressures of 103 Gbar, and inferred areal densities
      (rhoR) of 0.90  g/cm2 (shot N111215), values that are lower than 1D expectations
      by factors of 10*, 3.3*, and 1.5*, respectively. In this Letter, we present the
      design basis for an inertial confinement fusion capsule using an alternate
      indirect-drive pulse shape that is less sensitive to issues that may be
      responsible for this lower than expected performance. This new implosion features
      a higher radiation temperature in the "foot" of the pulse, three-shock pulse
      shape resulting in an implosion that has less sensitivity to the predicted
      ionization state of carbon, modestly lower convergence ratio, and significantly
      lower ablation Rayleigh-Taylor instability growth than that of the NIC point
      design capsule. The trade-off with this new design is a higher fuel adiabat that
      limits both fuel compression and theoretical capsule yield. The purpose of
      designing this capsule is to recover a more ideal one-dimensional implosion that
      is in closer agreement to simulation predictions. Early experimental results
      support our assertions since as of this Letter, a high-foot implosion has
      obtained a record DT yield of 2.4*10(15) neutrons (within ~70% of 1D simulation)
      with fuel rhoR=0.84  g/cm2 and an estimated ~1/3 of the yield coming from alpha
      particle self-heating.

PMID- 24580605
TI  - Chaotic neoclassical separatrix dissipation in parametric drift-wave decay.
AB  - Experiments and theory characterize a parametric decay instability between plasma
      drift waves when the nonlinear coupling is modified by an electrostatic barrier.
      Novel mode coupling terms representing enhanced dissipation and mode phase shifts
      are caused by chaotic separatrix crossings on the wave-ruffled separatrix.
      Experimental determination of these coupling terms is in broad agreement with new
      chaotic neoclassical transport analyses. 

PMID- 24580606
TI  - Two-color laser-plasma generation of terahertz radiation using a frequency
      tunable half harmonic of a femtosecond pulse.
AB  - We investigate for the first time, both experimentally and theoretically, low
      frequency terahertz (THz) emission from the ambient air ionized by a two-color
      femtosecond laser pulse containing, besides the fundamental-frequency main field,
      a weak additional field tunable near the frequency of the half harmonic. By
      controlling the mutual polarization and the powers of the main and additional
      fields, we determine the dependences of the THz power and polarization on the
      parameters of the two-color pulse. We also discover the resonantlike dependence
      of the THz yield on the frequency detuning of the additional field. The
      analytical formulas obtained using the model of the free-electron residual
      current density give an excellent agreement with the experimental results. 

PMID- 24580607
TI  - Quantum tricriticality at the superfluid-insulator transition of binary Bose
      mixtures.
AB  - Quantum criticality near a tricritical point is studied in the two-component Bose
      Hubbard model on square lattices. The existence of a quantum tricritical point on
      a boundary of a superfluid-insulator transition is confirmed by quantum Monte
      Carlo simulations. Moreover, we analytically derive the quantum tricritical
      behaviors on the basis of an effective field theory. We find two significant
      features of the quantum tricriticality that are its characteristic chemical
      potential dependence of the superfluid transition temperature and a strong
      density fluctuation. We suggest that these features are directly observable in
      existing experimental setups of Bose-Bose mixtures in optical lattices. 

PMID- 24580608
TI  - Efficient nonlinear generation of THz plasmons in graphene and topological
      insulators.
AB  - Surface plasmons in graphene may provide an attractive alternative to noble-metal
      plasmons due to their tighter confinement, peculiar dispersion, and longer
      propagation distance. We present theoretical studies of the nonlinear difference
      frequency generation (DFG) of terahertz surface plasmon modes supported by two
      dimensional layers of massless Dirac electrons, which includes graphene and
      surface states in topological insulators. Our results demonstrate strong
      enhancement of the DFG efficiency near the plasmon resonance and the feasibility
      of phase-matched nonlinear generation of plasmons over a broad range of
      frequencies. 

PMID- 24580609
TI  - Nanoscopic friction under electrochemical control.
AB  - We propose a theoretical model of friction under electrochemical conditions
      focusing on the interaction of a force microscope tip with adsorbed polar
      molecules whose orientation depends on the applied electric field. We demonstrate
      that the dependence of friction force on the electric field is determined by the
      interplay of two channels of energy dissipation: (i) the rotation of dipoles and
      (ii) slips of the tip over potential barriers. We suggest a promising strategy to
      achieve a strong dependence of nanoscopic friction on the external field based on
      the competition between long-range electrostatic interactions and short-range
      chemical interactions between tip and adsorbed polar molecules. 

PMID- 24580610
TI  - In operando GISAXS studies of mound coarsening in electrochemical homoepitaxy.
AB  - Kinetic roughening during electrodeposition was studied by grazing incidence
      small angle x-ray scattering for the case of Au(001) homoepitaxial growth in Cl-
      containing electrolytes. The formation and coarsening of an isotropic mound
      distribution on unreconstructed Au(001) and of [110]-oriented anisotropic mounds
      on the "hex" reconstructed surface was observed. The lateral mound coarsening is
      described by a well-defined scaling law. On unreconstructed Au a transition in
      the coarsening exponent from ~1/4 to ~1/3 with increasing potential is found,
      which can be explained by the pronounced potential dependence of surface
      transport processes in an electrochemical environment. 

PMID- 24580611
TI  - Electron-phonon coupling and the metallization of solid helium at terapascal
      pressures.
AB  - Solid He is studied in the pressure and temperature ranges 1-40 TPa and 0-10 000
      K using first-principles methods. Anharmonic vibrational properties are
      calculated within a self-consistent field framework, including the internal and
      free energies, density-pressure relation, stress tensor, thermal expansion, and
      the electron-phonon coupling renormalization of the electronic band gap. We find
      that an accurate description of electron-phonon coupling requires us to use a
      nonperturbative approach. The metallization pressure of 32.9 TPa at 0 K is larger
      than found previously. The vibrational effects are large; for example, at P=30 
      TPa the band gap is increased by 2.8 eV by electron-phonon coupling and a further
      0.1 eV by thermal expansion compared to the static value. The implications of the
      calculated metallization pressure for the cooling of white dwarfs are discussed. 

PMID- 24580612
TI  - Nanophononic metamaterial: thermal conductivity reduction by local resonance.
AB  - We present the concept of a locally resonant nanophononic metamaterial for
      thermoelectric energy conversion. Our configuration, which is based on a silicon
      thin film with a periodic array of pillars erected on one or two of the free
      surfaces, qualitatively alters the base thin-film phonon spectrum due to a
      hybridization mechanism between the pillar local resonances and the underlying
      atomic lattice dispersion. Using an experimentally fitted lattice-dynamics-based
      model, we conservatively predict the metamaterial thermal conductivity to be as
      low as 50% of the corresponding uniform thin-film value despite the fact that the
      pillars add more phonon modes to the spectrum. 

PMID- 24580613
TI  - Probing the glass transition from structural and vibrational properties of zero
      temperature glasses.
AB  - We find that the density dependence of the glass transition temperature of
      Lennard-Jones (LJ) and Weeks-Chandler-Andersen (WCA) systems can be predicted
      from properties of the zero-temperature (T=0) glasses. Below a crossover density
      rhos, LJ and WCA glasses show different structures, leading to different
      vibrational properties and consequently making LJ glasses more stable with higher
      glass transition temperatures than WCA ones. Above rhos, structural and
      vibrational quantities of the T=0 glasses show scaling collapse. From scaling
      relations and dimensional analysis, we predict a density scaling of the glass
      transition temperature, in excellent agreement with simulation results. We also
      propose an empirical expression of the glass transition temperature using
      structural and vibrational properties of the T=0 glasses, which works well over a
      wide range of densities. 

PMID- 24580614
TI  - Quantized thermal conductance of nanowires at room temperature due to Zenneck
      surface-phonon polaritons.
AB  - Based on the Landauer formalism, we demonstrate that the thermal conductance due
      to the propagation of Zenneck surface-phonon polaritons along a polar nanowire is
      independent of the material characteristics and is given by pi2kB2T/3h. The giant
      propagation length of these energy carriers establishes that this quantization
      holds not only for a temperature much smaller than 1 K, as is the case for
      electrons and phonons, but also for temperatures comparable to room temperature,
      which can significantly facilitate its observation and application in the thermal
      management of nanoscale electronics and photonics. 

PMID- 24580615
TI  - Novel high-pressure monoclinic metallic phase of V2O3.
AB  - Vanadium sesquioxide, V2O3, is a prototypical metal-to-insulator system where, in
      temperature-dependent studies, the transition always coincides with a corundum-to
      monoclinic structural transition. As a function of pressure, V2O3 follows the
      expected behavior of increased metallicity due to a larger bandwidth for
      pressures up to 12.5 GPa. Surprisingly, for higher pressures when the structure
      becomes unstable, the resistance starts to increase. Around 32.5 GPa at 300 K, we
      observe a novel pressure-induced corundum-to-monoclinic transition between two
      metallic phases, showing that the structural phase transition can be decoupled
      from the metal-insulator transition. Using x-ray Raman scattering, we find that
      screening effects, which are strong in the corundum phase, become weakened at
      high pressures. Theoretical calculations indicate that this can be related to a
      decrease in coherent quasiparticle strength, suggesting that the high-pressure
      phase is likely a critical correlated metal, on the verge of Mott-insulating
      behavior. 

PMID- 24580616
TI  - Novel magnetism of Ir5+(5d4) Ions in the double perovskite Sr2YIrO6.
AB  - We synthesize and study single crystals of a new double-perovskite Sr2YIrO6.
      Despite two strongly unfavorable conditions for magnetic order, namely,
      pentavalent Ir5+(5d4) ions which are anticipated to have Jeff=0 singlet ground
      states in the strong spin-orbit coupling (SOC) limit and geometric frustration in
      a face-centered cubic structure formed by the Ir5+ ions, we observe this iridate
      to undergo a novel magnetic transition at temperatures below 1.3 K. We provide
      compelling experimental and theoretical evidence that the origin of magnetism is
      in an unusual interplay between strong noncubic crystal fields, local exchange
      interactions, and "intermediate-strength" SOC. Sr2YIrO6 provides a rare example
      of the failed dominance of SOC in the iridates. 

PMID- 24580617
TI  - Current-induced spin polarization in anisotropic spin-orbit fields.
AB  - The magnitude and direction of current-induced spin polarization and spin-orbit
      splitting are measured in In0.04Ga0.96 As epilayers as a function of in-plane
      electric and magnetic fields. We show that, contrary to expectation, the
      magnitude of the current-induced spin polarization is smaller for crystal
      directions corresponding to larger spin-orbit fields. Furthermore, we find that
      the steady-state in-plane spin polarization does not align along the spin-orbit
      field, an effect due to anisotropy in the spin relaxation rate. 

PMID- 24580618
TI  - Spin heat accumulation induced by tunneling from a ferromagnet.
AB  - An electric current from a ferromagnet into a nonmagnetic material can induce a
      spin-dependent electron temperature. Here, it is shown that this spin heat
      accumulation, when created by tunneling from a ferromagnet, produces a non
      negligible voltage signal that is comparable to that due to the coexisting
      electrical spin accumulation and can give a different Hanle spin precession
      signature. The effect is governed by the spin polarization of the Peltier
      coefficient of the tunnel contact, its Seebeck coefficient, and the spin heat
      resistance of the nonmagnetic material, which is related to the electrical spin
      resistance by a spin-Wiedemann-Franz law. Moreover, spin heat injection is
      subject to a heat conductivity mismatch that is overcome if the tunnel interface
      has a sufficiently large resistance. 

PMID- 24580619
TI  - Chemical-potential-dependent gap opening at the Dirac surface states of Bi2Se3
      induced by aggregated substitutional Cr atoms.
AB  - With angle-resolved photoemission spectroscopy, gap opening is resolved at up to
      room temperature in the Dirac surface states of molecular beam epitaxy grown Cr
      doped Bi2Se3 topological insulator films, which, however, show no long-range
      ferromagnetic order down to 1.5 K. The gap size is found decreasing with
      increasing electron-doping level. Scanning tunneling microscopy and first
      principles calculations demonstrate that substitutional Cr atoms aggregate into
      superparamagnetic multimers in the Bi2Se3 matrix, which contribute to the
      observed chemical-potential-dependent gap opening in the Dirac surface states
      without long-range ferromagnetic order. 

PMID- 24580620
TI  - Plasmon-enhanced four-wave mixing for superresolution applications.
AB  - We introduce a nonlinear optical approach to transform spatial information stored
      in evanescent waves into propagating ones: we study analytically the use of
      partially degenerate four-wave mixing in thin metallic film to map a band of
      evanescent waves at a given frequency into a propagating-wave band at a different
      one. The relatively low efficiency of this process is compensated by setting the
      pump beam, mediating this transformation, to be a surface plasmon polariton,
      whose field enhancement increases the nonlinear interaction strength. This
      setting can be utilized for nonresonant plasmon-assisted superresolution
      applications that support transverse-electric polarization, in contrast to linear
      plasmonic imaging (such as superlens) that can only transfer transverse-magnetic
      waves. 

PMID- 24580622
TI  - Repulsive Casimir effect with Chern insulators.
AB  - We theoretically predict that the Casimir force in vacuum between two Chern
      insulator plates can be repulsive (attractive) at long distances whenever the
      sign of the Chern numbers characterizing the two plates are opposite (equal). A
      unique feature of this system is that the sign of the force can be tuned simply
      by turning over one of the plates or alternatively by electrostatic doping. We
      calculate and take into account the full optical response of the plates and argue
      that such repulsion is a general phenomena for these systems as it relies on the
      quantized zero frequency Hall conductivity. We show that achieving repulsion is
      possible with thin films of Cr-doped (Bi,Sb)2Te3, that were recently discovered
      to be Chern insulators with quantized Hall conductivity. 

PMID- 24580621
TI  - Charge tuning of nonresonant magnetoexciton phonon interactions in graphene.
AB  - Far from resonance, the coupling of the G-band phonon to magnetoexcitons in
      single layer graphene displays kinks and splittings versus filling factor that
      are well described by Pauli blocking and unblocking of inter- and intra-Landau
      level transitions. We explore the nonresonant electron-phonon coupling by high
      magnetic field Raman scattering while electrostatic tuning of the carrier density
      controls the filling factor. We show qualitative and quantitative agreement
      between spectra and a linearized model of electron-phonon interactions in
      magnetic fields. The splitting is caused by dichroism of left- and right-handed
      circular polarized light due to lifting of the G-band phonon degeneracy, and the
      piecewise linear slopes are caused by the linear occupancy of sequential Landau
      levels versus nu. 

PMID- 24580623
TI  - Predicted very large thermoelectric effect in ferromagnet-superconductor
      junctions in the presence of a spin-splitting magnetic field.
AB  - We show that a huge thermoelectric effect can be observed by contacting a
      superconductor whose density of states is spin split by a Zeeman field with a
      ferromagnet with a nonzero polarization. The resulting thermopower exceeds kB/e
      by a large factor, and the thermoelectric figure of merit ZT can far exceed
      unity, leading to heat engine efficiencies close to the Carnot limit. We also
      show that spin-polarized currents can be generated in the superconductor by
      applying a temperature bias. 

PMID- 24580625
TI  - Order by disorder spin wave gap in the XY pyrochlore magnet Er2Ti2O7.
AB  - The recent determination of a robust spin Hamiltonian for the antiferromagnetic
      XY pyrochlore Er2Ti2O7 reveals a most convincing case of the "Order-by-Quantum
      Disorder" mechanism for ground state selection. This mechanism relies on quantum
      fluctuations to remove an accidental symmetry of the magnetic ground state, and
      selects a particular ordered spin structure below TN=1.2 K. The removal of the
      continuous degeneracy results in an energy gap in the spectrum of spin wave
      excitations, long wavelength pseudo-Goldstone modes. We have measured the Order
      by-Quantum-Disorder spin wave gap at a zone center in Er2Ti2O7, using low
      incident energy neutrons and the time-of-flight inelastic scattering method. We
      report a gap of Delta=0.053+/-0.006  meV, which is consistent with upper bounds
      placed on it from heat capacity measurements and roughly consistent with the
      theoretical estimate of ~0.02  meV, further validating the spin Hamiltonian that
      led to that prediction. The gap is observed to vary with the square of the order
      parameter, and goes to zero for T~TN. 

PMID- 24580624
TI  - Imaging the electron-boson coupling in superconducting FeSe films using a
      scanning tunneling microscope.
AB  - Scanning tunneling spectroscopy has been used to reveal signatures of a bosonic
      mode in the local quasiparticle density of states of superconducting FeSe films.
      The mode appears below Tc as a "dip-hump" feature at energy Omega~4.7kBTc beyond
      the superconducting gap Delta. Spectra on strained regions of the FeSe films
      reveal simultaneous decreases in Delta and Omega. This contrasts with all
      previous reports on other high-Tc superconductors, where Delta locally
      anticorrelates with Omega. A local strong coupling model is found to reconcile
      the discrepancy well, and to provide a unified picture of the electron-boson
      coupling in unconventional superconductors. 

PMID- 24580626
TI  - Prediction of a novel magnetoelectric switching mechanism in multiferroics.
AB  - We report a first-principles study of the recently predicted Pmc21 phase of the
      multiferroic BiFeO3 material, revealing a novel magnetoelectric effect that makes
      it possible to control magnetism with an electric field. The effect can be viewed
      as a two-step process: Switching the polarization first results in the change of
      the sense of the rotation of the oxygen octahedra, which in turn induces the
      switching of the secondary magnetic order parameter. The first step is governed
      by an original trilinear-coupling energy between polarization, octahedral
      tilting, and an antiferroelectric distortion. The second step is controlled by
      another trilinear coupling, this one involving the predominant and secondary
      magnetic orders as well as the oxygen octahedral tilting. In contrast with other
      trilinear-coupling effects in the literature, the present ones occur in a simple
      ABO3 perovskite and involve a large polarization. 

PMID- 24580627
TI  - Universal behavior beyond multifractality in quantum many-body systems.
AB  - How many states of a configuration space contribute to a wave function? Attempts
      to answer this ubiquitous question have a long history in physics and are keys to
      understanding, e.g., localization phenomena. Beyond single-particle physics, a
      quantitative study of the ground state complexity for interacting many-body
      quantum systems is notoriously difficult, mainly due to the exponential growth of
      the configuration (Hilbert) space with the number of particles. Here we develop
      quantum Monte Carlo schemes to overcome this issue, focusing on Shannon-Renyi
      entropies of ground states of large quantum many-body systems. Our simulations
      reveal a generic multifractal behavior while the very nature of quantum phases of
      matter and associated transitions is captured by universal subleading terms in
      these entropies. 

PMID- 24580628
TI  - Proposed entanglement of X-ray nuclear polaritons as a potential method for
      probing matter at the subatomic scale.
AB  - A setup for generating the special superposition of a simultaneously forward- and
      backward-propagating collective excitation in a nuclear sample is studied. We
      show that by actively manipulating the scattering channels of single x-ray quanta
      with the help of a normal incidence x-ray mirror, a nuclear polariton which
      propagates in two opposite directions can be generated. The two
      counterpropagating polariton branches are entangled by a single x-ray photon. The
      quantum nature of the nuclear excitation entanglement gives rise to a subangstrom
      wavelength standing wave excitation pattern that can be used as a flexible tool
      to probe matter dynamically on the subatomic scale. 

PMID- 24580630
TI  - Ratcheting and transitions: short granular chain in a gradient of vibration.
AB  - We report our experimental work on a one-dimensional gradient of vibration with a
      short granular chain. The system exhibits transitions of ratcheting dynamics from
      passive monotonic creeping against the gradient, to rapid stochastic head
      swinging with a reversed bias in its direction, and to seemingly random
      fluctuations. The spontaneously emerged spatial pattern reflects bifurcations of
      the state of the chain. Evidence from counterpart experiments using uniform
      vibrations confirms a nonmonotonic development of accessible modes behind the
      transitions, whereas the reversed ratcheting reflects an interesting dialogue
      between the size of the object and the spatial gradient. 

PMID- 24580629
TI  - Spin texture of Bi2Se3 thin films in the quantum tunneling limit.
AB  - By means of spin- and angle-resolved photoelectron spectroscopy we studied the
      spin structure of thin films of the topological insulator Bi2Se3 grown on
      InP(111). For thicknesses below six quintuple layers the spin-polarized metallic
      topological surface states interact with each other via quantum tunneling and a
      gap opens. Our measurements show that the resulting surface states can be
      described by massive Dirac cones which are split in a Rashba-like manner due to
      the substrate induced inversion asymmetry. The inner and the outer Rashba
      branches have distinct localization in the top and the bottom part of the film,
      whereas the band apices are delocalized throughout the entire film. Supported by
      calculations, our observations help in the understanding of the evolution of the
      surface states at the topological phase transition and provide the groundwork for
      the realization of two-dimensional spintronic devices based on topological
      semiconductors. 

PMID- 24580631
TI  - Phonon quasiparticles and anharmonic free energy in complex systems.
AB  - We use a hybrid strategy to obtain anharmonic frequency shifts and lifetimes of
      phonon quasiparticles from first principles molecular dynamics simulations in
      modest size supercells. This approach is effective irrespective of crystal
      structure complexity and facilitates calculation of full anharmonic phonon
      dispersions, as long as phonon quasiparticles are well defined. We validate this
      approach to obtain anharmonic effects with calculations in MgSiO3 perovskite, the
      major Earth forming mineral phase. First, we reproduce irregular thermal
      frequency shifts of well characterized Raman modes. Second, we combine the phonon
      gas model (PGM) with quasiparticle frequencies and reproduce free energies
      obtained using thermodynamic integration. Combining thoroughly sampled
      quasiparticle dispersions with the PGM we then obtain first-principles anharmonic
      free energy in the thermodynamic limit (N->infinity). 

PMID- 24580632
TI  - Comment on "Robust formation of skyrmions and topological Hall effect anomaly in
      epitaxial thin films of MnSi".

PMID- 24580633
TI  - Li et al. reply.

PMID- 24580635
TI  - Structure-activity relationship refinement and further assessment of 4
      phenylquinazoline-2-carboxamide translocator protein ligands as antiproliferative
      agents in human glioblastoma tumors.
AB  - Structure-activity relationships (SARs) within the 4-phenylquinazoline-2
      carboxamide series of translocator protein (TSPO) ligands have been explored
      further by the synthesis and TSPO binding affinity evaluation of N-benzyl-N
      ethyl/methyl derivatives variously decorated at the 6-, 2'-, 4'-, and 4"
      positions. Most of the compounds showed high affinity with K(i) values in the
      nanomolar/subnanomolar range. A pharmacophore model was developed and employed to
      better address SAR data presented by the new TSPO ligands. A subset of the new
      compounds (5, 8, 12, and 19) were tested for their ability to inhibit the
      viability of human glioblastoma cell line U343. The observed antiproliferative
      effect was demonstrated to be specific for compound 19, endowed with the best
      combination of binding affinity and efficacy. Furthermore, the ability of 19 to
      induce mitochondrial membrane dissipation (Deltapsi(m)) substantiated the
      intracellular pro-apoptotic mechanism activated by the binding of this class of
      ligands to TSPO.

PMID- 24580636
TI  - "That was grown folks' business": narrative reflection and response in older
      adults' family health history communication.
AB  - Given the importance of family health history and the pivotal role of older
      adults in communicating it, this study examines how African American older adults
      (a) characterize their understandings of health-related conditions in their
      family histories and (b) rationalize their motivations and constraints for
      sharing this information with current family members. Using narrative theory as a
      framework, we illustrate how the participants reflect on prior health-related
      experiences within the family to respond to moral and practical calls for
      communicating family health information to current relatives. Specifically, our
      analysis highlights how storied family secrets--as constructed by 28 participants
      in group and individual interviews--reveal and inform shifting cultural and
      generational practices that shape the lived health behaviors and communication of
      older adults at greater risk for health disparities.

PMID- 24580637
TI  - The influences of optimal matching and social capital on communicating support.
AB  - The optimal matching and social capital perspectives frame present research
      expectations and interpretations of the network, esteem, informational, and
      emotional support communication of 3 computer-mediated communication social
      support groups, each having a different health-promoting purpose. Past research
      has shown differences in the support communication provided by different groups
      but has offered little explanation for these differences. The present study uses
      a comparative analysis of optimal matching and social capital influences to
      compare and analyze differences in the support communication provided by
      Alcoholics Anonymous, cancer caregivers, and transgender identity support groups.
      Results show different patterns of support communication enacted in each. These
      results provide support for optimal matching and social capital predictions,
      indicating that the life stressor and group structure affect the social support
      provided. However, results also demonstrate a need for greater refinement in
      interpreting the effects of these influences. Each group communicates network,
      esteem, informational, and emotional support somewhat differently in response to
      the life stressor and in enacting bridging and bonding social capital. The
      present comparisons provide a fuller analysis of the optimal matching and social
      capital influences upon the support communicated in groups than afforded by past
      research studies and suggests research opportunities for future research. 

PMID- 24580639
TI  - Equine grass sickness.
AB  - Equine grass sickness (EGS; equine dysautonomia) is a polyneuronopathy affecting
      both the central and the peripheral nervous systems of horses. As the name
      implies, EGS almost exclusively affects grazing horses, resulting in the
      development of a characteristic array of clinical signs, most of which can be
      attributed to neuronal degeneration in the autonomic and enteric nervous systems.
      Varying disease severities occur, largely determined by the extent of neuronal
      degeneration in the myenteric and submucous plexuses of the enteric nervous
      system. Extensive neuronal degeneration, as seen in acute and subacute forms of
      EGS, results in intestinal dysmotility, the severity of which is incompatible
      with survival. In comparison, a proportion of chronic forms of EGS, characterised
      by less severe neuronal degeneration, will survive. Despite extensive research
      efforts since EGS was first reported over 100 years ago, the precise aetiology
      remains elusive. This article reviews much of the scientific literature on EGS,
      covering epidemiology, pathology, diagnosis, treatment and aetiological
      hypotheses. 

PMID- 24580634
TI  - Nucleic acid oxidation in DNA damage repair and epigenetics.

PMID- 24580640
TI  - Desialylation of dying cells with catalytically active antibodies possessing
      sialidase activity facilitate their clearance by human macrophages.
AB  - Recently we reported the first known incidence of antibodies possessing catalytic
      sialidase activity (sialidase abzymes) in the serum of patients with multiple
      myeloma and systemic lupus erythematosus (SLE). These antibodies desialylate
      biomolecules, such as glycoproteins, gangliosides and red blood cells.
      Desialylation of dying cells was demonstrated to facilitate apoptotic cell
      clearance. In this study we assessed the possibility to facilitate dying cell
      clearance with the use of F(ab)2 fragments of sialidase abzymes. Two sources of
      sialidase abzymes were used: (i) those isolated from sera of patients with SLE
      after preliminary screening of a cohort of patients for sialidase activity; and
      (ii) by creating an induced sialidase abzyme through immunization of a rabbit
      with synthetic hapten consisting of a non-hydrolysable analogue of sialidase
      reaction conjugated with bovine serum albumin (BSA) or keyhole limpet haemocyanin
      (KLH). Antibodies were purified by ammonium sulphate precipitation, protein-G
      affinity chromatography and size exclusion-high performance liquid chromatography
      (HPLC-SEC). Effect of desialylation on efferocytosis was studied using human
      polymorphonuclear leucocytes (PMN), both viable and aged, as prey, and human
      monocyte-derived macrophages (MoMa). Treatment of apoptotic and viable prey with
      both disease-associated (purified from blood serum of SLE patients) and
      immunization-induced (obtained by immunization of rabbits) sialidase abzymes, its
      F(ab)2 fragment and bacterial neuraminidase (as positive control) have
      significantly enhanced the clearance of prey by macrophages. We conclude that
      sialidase abzyme can serve as a protective agent in autoimmune patients and that
      artificial abzymes may be of potential therapeutic value. 

PMID- 24580641
TI  - Selection-based discovery of druglike macrocyclic peptides.
AB  - Macrocyclic peptides are an emerging class of therapeutics that can modulate
      protein-protein interactions. In contrast to the heavily automated high
      throughput screening systems traditionally used for the identification of
      chemically synthesized small-molecule drugs, peptide-based macrocycles can be
      synthesized by ribosomal translation and identified using in vitro selection
      techniques, allowing for extremely rapid (hours to days) screening of compound
      libraries comprising more than 10(13) different species. Furthermore, chemical
      modification of translated peptides and engineering of the genetic code have
      greatly expanded the structural diversity of the available peptide libraries. In
      this review, we discuss the use of these technologies for the identification of
      bioactive macrocyclic peptides, emphasizing recent developments. 

PMID- 24580642
TI  - Biosynthesis and export of bacterial lipopolysaccharides.
AB  - Lipopolysaccharide molecules represent a unique family of glycolipids based on a
      highly conserved lipid moiety known as lipid A. These molecules are produced by
      most gram-negative bacteria, in which they play important roles in the integrity
      of the outer-membrane permeability barrier and participate extensively in host
      pathogen interplay. Few bacteria contain lipopolysaccharide molecules composed
      only of lipid A. In most forms, lipid A is glycosylated by addition of the core
      oligosaccharide that, in some bacteria, provides an attachment site for a long
      chain O-antigenic polysaccharide. The complexity of lipopolysaccharide structures
      is reflected in the processes used for their biosynthesis and export. Rapid
      growth and cell division depend on the bacterial cell's capacity to synthesize
      and export lipopolysaccharide efficiently and in large amounts. We review recent
      advances in those processes, emphasizing the reactions that are essential for
      viability. 

PMID- 24580643
TI  - High-resolution structure of the eukaryotic 80S ribosome.
AB  - The high-resolution structure of the eukaryotic ribosome from yeast, determined
      at 3.0-A resolution, permitted the unambiguous determination of the protein side
      chains, eukaryote-specific proteins, protein insertions, and ribosomal RNA
      expansion segments of the 80 proteins and ~5,500 RNA bases that constitute the
      80S ribosome. A comparison between this first atomic model of the entire 80S
      eukaryotic ribosome and previously determined structures of bacterial ribosomes
      confirmed early genetic and structural data indicating that they share an
      evolutionarily conserved core of ribosomal RNA and proteins. It also confirmed
      the conserved organization of essential functional sites, such as the peptidyl
      transferase center and the decoding site. New structural information about
      eukaryote-specific elements, such as expansion segments and new ribosomal
      proteins, forms the structural framework for the design and analysis of
      experiments that will explore the eukaryotic translational apparatus and the
      evolutionary forces that shaped it. New nomenclature for ribosomal proteins,
      based on the names of protein families, has been proposed. 

PMID- 24580644
TI  - Understanding anisotropic plasma etching of two-dimensional polystyrene opals for
      advanced materials fabrication.
AB  - Anisotropic deformation of polystyrene particles in an oxygenated (O2/Ar) plasma
      is observed for radio frequency (rf) plasma and inductively coupled plasma (ICP).
      A facile model based on a ratio of completely isotropic and completely
      anisotropic etching is presented to describe the anisotropy of the etching
      process and is implemented to determine the height of the spheroid-shaped
      polystyrene particles. In our systems, we find the plasma etching to be 54%
      isotropic in the rf plasma and 79% isotropic in the ICP. With this model, the
      maximum material deposition thickness for nanofabrication with plasma-etched
      nanosphere lithography or colloid lithography can be predicted. Moreover, the
      etching of polystyrene particles in an oxygenated plasma is investigated versus
      the etching time, gas flow, gas composition, temperature, substrate material, and
      particle size. The results of this study allow precise shape tuning during the
      fabrication of nanostructured surfaces with size-dependent properties for bionic,
      medical, and photonic applications. 

PMID- 24580645
TI  - Spontaneous healing and complete disappearance of a ruptured posterior inferior
      cerebellar artery dissecting aneurysm.
AB  - A 7-month-old baby presented with a 4-day history of drowsiness and vomiting
      after a falling accident. Magnetic resonance imaging demonstrated diffuse
      subarachnoid hemorrhage, intraventricular hemorrhage, and variable stages of
      subdural hematoma in bilateral occipital and left temporal subdural spaces. A
      partially thrombosed aneurysm was noted in the right craniocervical junction.
      Ophthalmological examination revealed bilateral retinal petechial hemorrhages.
      Conventional cerebral angiography revealed a dissecting aneurysm in the right
      posterior inferior cerebellar artery (PICA). Endovascular embolization was
      suggested, but the family refused. After conservative treatment, follow-up MRI
      revealed that the PICA aneurysm had remodeled and ultimately disappeared
      completely at the 10th month. This case illustrates the relatively plastic nature
      of intracranial aneurysms in pediatric patients. More studies are necessary to
      clarify the natural history of spontaneously thrombosed aneurysms to assist in
      their overall management. 

PMID- 24580646
TI  - Costs and benefits of PAS platelets: a mix of science, quality, and value.

PMID- 24580647
TI  - Leukapheresis: have we been looking at the right outcome?

PMID- 24580649
TI  - Maintenance of coagulation factor activities and protein levels of frozen plasma
      and cryoprecipitate AHF following 1 year's storage at -30  degrees C with two 8
      hour temperature excursions to -10  degrees C.

PMID- 24580650
TI  - Intermittent spirochetemia in SKH mice infected with Borrelia burgdorferi, sensu
      stricto.

PMID- 24580651
TI  - Delayed hemolytic transfusion reaction, intravenous immunoglobulin, and
      rituximab.

PMID- 24580652
TI  - Fetal middle cerebral and umbilical artery Doppler after 40 weeks gestational
      age.
AB  - OBJECTIVE: To determine the value of fetal Doppler indices named middle cerebral
      artery (MCA)-PI, umbilical artery (UA)-PI and MCA-PI/UA-PI ratio, and amniotic
      fluid volume assessment in pregnancies 280-294 d and their correlation with the
      mode of delivery and perinatal outcome. STUDY DESIGN: Prospective observational
      study conducted on 100 whose gestational age (GA) from 40 to 42 weeks. MCA and UA
      Doppler and MCA-PI/UA-PI ratio, amniotic fluid volume (AFV) were assessed. They
      were divided into two groups based on the presence or absence of adverse
      perinatal outcome. RESULTS: Women with adverse perinatal outcome showed lower MCA
      PI (0.92 versus 1.29), MCA-PI:UA-PI ratio (1.04 versus 1.83), lower gestational
      age when assessed by ultrasound (37.82 versus 39.48 weeks), lower neonatal birth
      weight (2705 versus 3108 g), fetal biophysical profile (BPP) (4.55 versus 7.21)
      when compared to women with normal perinatal outcome. They also had higher cases
      with oligohydramnios (34 versus 5), and higher UA-PI (0.89 versus 0.72).
      CONCLUSION: Women with adverse neonatal outcome had higher UA-PI and lower MCA
      PI, MCA-PI:UA-PI ratio, GA (by US), AFV, BPP, estimated fetal weight, neonatal
      birth weight when compared to those with normal perinatal outcome. Women with
      adverse neonatal outcome had a higher rate of cesarean section mostly due to
      fetal distress and induced VD due to oligohydraminos compared to the normal
      outcome group.

PMID- 24580653
TI  - Editorial.

PMID- 24580656
TI  - Gordon John Howes 1938-2013 (fish systematist).

PMID- 24580655
TI  - Early reproductive investment, senescence and lifetime reproductive success in
      female Asian elephants.
AB  - The evolutionary theory of senescence posits that as the probability of extrinsic
      mortality increases with age, selection should favour early-life over late-life
      reproduction. Studies on natural vertebrate populations show early reproduction
      may impair later-life performance, but the consequences for lifetime fitness have
      rarely been determined, and little is known of whether similar patterns apply to
      mammals which typically live for several decades. We used a longitudinal dataset
      on Asian elephants (Elephas maximus) to investigate associations between early
      life reproduction and female age-specific survival, fecundity and offspring
      survival to independence, as well as lifetime breeding success (lifetime number
      of calves produced). Females showed low fecundity following sexual maturity,
      followed by a rapid increase to a peak at age 19 and a subsequent decline. High
      early life reproductive output (before the peak of performance) was positively
      associated with subsequent age-specific fecundity and offspring survival, but
      significantly impaired a female's own later-life survival. Despite the negative
      effects of early reproduction on late-life survival, early reproduction is under
      positive selection through a positive association with lifetime breeding success.
      Our results suggest a trade-off between early reproduction and later survival
      which is maintained by strong selection for high early fecundity, and thus
      support the prediction from life history theory that high investment in
      reproductive success in early life is favoured by selection through lifetime
      fitness despite costs to later-life survival. That maternal survival in elephants
      depends on previous reproductive investment also has implications for the success
      of (semi-)captive breeding programmes of this endangered species. 

PMID- 24580657
TI  - Spatial and temporal variation in the diet of the Pacific sand lance Ammodytes
      hexapterus in waters off the coast of British Columbia, Canada.
AB  - Variation in the diet of the Pacific sand lance Ammodytes hexapterus was examined
      in three years (2009-2011) at four sites in British Columbia, Canada. There were
      12 major taxa of prey in diets, eight of which were Crustacea, with copepods
      being by far the dominant taxon in all 12 site-years. Of the 22 copepod taxa
      recorded, only Calanus marshallae and Pseudocalanus spp. occurred in all
      collections, and these two calanoid species dominated diets in terms of frequency
      of occurrence and total numbers of prey (Pseudocalanus spp. in most collections),
      and total prey biomass (C. marshallae in all collections). Based on an index of
      relative importance, C. marshallae was the primary prey at the two southerly
      sampling sites (Pine and Triangle Islands) and Pseudocalanus spp. at the two
      northerly sites (Lucy Island and S'Gang Gwaay). Based on an index of dietary
      overlap, the species composition of the copepod component of A. hexapterus diets
      overlapped very strongly at the northerly and the southerly pairs of sites in
      both a cold-water La Nina year (2009) and a warm-water El Nino year (2010), but
      overall there was more homogeneity amongst all four sites in the La Nina year. 

PMID- 24580658
TI  - Catch composition, reproductive biology and diet of the bramble shark
      Echinorhinus brucus (Squaliformes: Echinorhinidae) from the south-eastern Arabian
      Sea.
AB  - Fishery and biological data are presented for the poorly known bramble shark
      Echinorhinus brucus (Squaliformes: Echinorhinidae), from the deep waters of the
      south-eastern Arabian Sea. A total of 5318 individuals from by-catch landings of
      deep-water bottom set longlines, gillnets and shrimp trawl fisheries operating at
      depths of 200-1200 m were recorded between January 2008 and December 2011 at the
      Kochi Fisheries Harbour (Kerala). A total of 431 individuals, from 46 to 318 cm
      total length (L(T)) and 0.8 to 132 kg total mass (M(T)), were examined to
      determine biological data for this species. The LT at which 50% were mature
      (L(T)50) for females and males was estimated at 189 and 187 cm LT. Litter size
      ranged from 10 to 36 and size at birth was between 42 and 46 cm L(T). Dietary
      analysis of stomach contents revealed E. brucus feeds on a variety of prey
      including crustaceans (69% index of relative importance, I(RI)), teleosts (25.8%
      I(RI)), cephalopods (1.7% I(RI)) and elasmobranchs (0.7% I(RI)). This study
      provides the first detailed biological data for this species and also highlights
      the extent of the by-catch fishery for this species in Indian waters.

PMID- 24580659
TI  - Two new species of Leporinus (Characiformes: Anostomidae) from the Brazilian
      Amazon, and redescription of Leporinus striatus Kner 1858.
AB  - Two new species of Leporinus are described from tributaries of the Rio Amazonas
      in Brazil. One species is known from the Jari and Tapajos River basins, and is
      identified on the basis of a gas bladder reduced in size, a dark midlateral
      stripe on the body, dark transverse bars on the dorsum, a subinferior mouth,
      three teeth on the premaxilla, four teeth on the dentary and 16 scale rows around
      the caudal peduncle. The second new species is known from the Tocantins, Xingu
      and Tapajos River basins, and is identified on the basis of three dark
      longitudinal stripes on the body, a subinferior mouth, three teeth on the
      premaxilla, four teeth on the dentary and 12 scale rows around the caudal
      peduncle. In addition, Leporinus striatus is redescribed based on type and
      additional specimens from the Rio de La Plata, Amazonas, Orinoco, Atrato,
      Magdalena and Sinu River basins. Leporinus striatus is identified on the basis of
      four dark longitudinal stripes on the body, a subterminal mouth, three teeth on
      the premaxilla, four teeth on the dentary and 16 scale rows around the caudal
      peduncle. 

PMID- 24580661
TI  - Risk-taking behaviour may explain high predation mortality of GH-transgenic
      common carp Cyprinus carpio.
AB  - The competitive ability and habitat selection of juvenile all-fish GH-transgenic
      common carp Cyprinus carpio and their size-matched non-transgenic conspecifics,
      in the absence and presence of predation risk, under different food
      distributions, were compared. Unequal-competitor ideal-free-distribution analysis
      showed that a larger proportion of transgenic C. carpio fed within the system,
      although they were not overrepresented at a higher-quantity food source.
      Moreover, the analysis showed that transgenic C. carpio maintained a faster
      growth rate, and were more willing to risk exposure to a predator when foraging,
      thereby supporting the hypothesis that predation selects against maximal growth
      rates by removing individuals that display increased foraging effort. Without
      compensatory behaviours that could mitigate the effects of predation risk, the
      escaped or released transgenic C. carpio with high-gain and high-risk performance
      would grow well but probably suffer high predation mortality in nature. 

PMID- 24580660
TI  - Diversity of movements by individual anadromous coastal cutthroat trout
      Oncorhynchus clarkii clarkii.
AB  - Wild, downstream-migrating cutthroat trout, Oncorhynchus clarkii clarkii, smolts
      and adults were captured at a weir in Big Beef Creek, Hood Canal, Washington,
      surgically implanted with acoustic tags and tracked to identify spring and summer
      movements using stationary receivers in order to test the assumption that the
      species moves little while in marine waters. Overall, 93-96% migrated from the
      stream into the east side of the long narrow fjord, where they dispersed north
      and south along the shoreline. Most O. c. clarkii were detected nearshore within
      10 km of the release site, with declining detection rates to 77 km. Over one
      third (36%) crossed c. 2-4 km of deep water to the other side but only one O. c.
      clarkii left the Hood Canal basin. Movements and behaviour patterns did not
      differ between smolts and adults but cluster analysis revealed two modes of
      distribution, here categorized as residents and migrants. Within these categories
      of overall distribution, a range of finer-scale behaviour patterns was observed,
      including sedentary individuals, daily moving between proximate sites and more
      continuous long-distance travel. Diel movement patterns varied markedly among
      individuals but overall activity increased near dawn, peaked around mid-day and
      declined but continued at night. These patterns contrast with sympatric and
      closely related steelhead trout, Oncorhynchus mykiss, providing new insights into
      the diversity of salmonid behaviour. 

PMID- 24580662
TI  - Long-term effects of photoperiod, temperature and their interaction on growth,
      gill Na+, K+-ATPase activity, seawater tolerance and plasma growth-hormone levels
      in Atlantic salmon Salmo salar.
AB  - This study was undertaken to examine the long-term effects of photoperiod,
      temperature and their interaction on growth, gill Na+,K+-ATPase (NKA) activity,
      seawater tolerance and plasma growth-hormone levels in Atlantic salmon Salmo
      salar pre-smolts and smolts. The fish (mean +/- s.e. initial body mass = 15.9 +/-
      0.4 g) were reared on two photoperiods (continuous light, LL, and simulated
      natural photoperiod, LDN, 60 degrees  25' N) and two temperatures (8.3 and 12.7
      degrees  C) from June to May of the following year. Mean body mass was affected
      by photoperiod, temperature and their interactions. Both temperature groups on LL
      developed peak levels in gill NKA activity from October to November, 4-5 months
      prior to the natural season for the parr-smolt transformation. Fish at 12 degrees
      C showed peak levels in NKA activity 4-6 weeks before the fish at 8 degrees  C.
      Fish in all four experimental groups showed maximum NKA activity within a similar
      size range (113-162 g). The present findings further indicate that smoltification
      in S. salar is to some extent driven by size, and that S. salar will develop
      smolt characteristics, e.g. a marked increase in NKA activity, within a similar
      size range. Faster-growing S. salar will, thus, reach this size threshold at a
      relatively younger age.

PMID- 24580663
TI  - From gelatinous to muscle food chain: rock cod Patagonotothen ramsayi recycles
      coelenterate and tunicate resources on the Patagonian Shelf.
AB  - Stomach contents of 4808 fishes of 20 species caught in the eastern part of the
      Patagonian Shelf between 1999 and 2012 were analysed to assess dietary
      contributions of gelatinous plankton resources. Gelatinous plankton occurred in
      diets of seven species with two species, Patagonotothen ramsayi and Squalus
      acanthias, having >10% ctenophores in their diet. Consumption of gelatinous
      plankton was important in P. ramsayi and was strikingly seasonal, with maximum
      occurrence (up to 46% of non-empty stomachs) in late summer to autumn.
      Ctenophores were most abundant in P. ramsayi of 25-34 cm total length, L(T)
      whereas salps were more frequent in larger >35 cm L(T) individuals. In winter to
      spring, occurrence of gelatinous plankton in diets was minimal, reflecting their
      overall seasonal abundance in the ocean. The recent increase in abundance of P.
      ramsayi has enabled the species to recycle a significant proportion of the
      ecosystem production from gelatinous dead end to the main muscular food chain via
      seasonal reliance on ctenophores, jellyfish and tunicates. This additional influx
      of production that has been diverted from the gelatinous food chain favours the
      increase in abundance of several piscivorous top predators and affects the
      trophic web structure of the Patagonian Shelf ecosystem.

PMID- 24580664
TI  - Adhesion mechanisms in European whitefish Coregonus lavaretus eggs: is this a
      survival mechanism for high-energy spawning grounds?
AB  - This study examined the potential biochemical and mechanical structures that may
      contribute to egg adhesion in European whitefish Coregonus lavaretus. Experiments
      showed that eggs from a population of C. lavaretus from Loch Eck remained non
      adhesive in a solution chemically similar to ovarian fluid but became adhesive
      seconds after contact with water. Examination of the ultrastructure of the
      chorion showed that the morphology changed significantly after contact with
      water, with nodule-like protuberances attached to connective filaments on the
      surface present in water-hardened but not non-water hardened eggs. Biochemical
      analysis showed the presence of Chain A, RNase ZF-3e proteins in the chorion of
      water-hardened but not non-water hardened eggs. Histochemical staining of the
      chorion of C. lavaretus eggs showed that the externa, but not the interna,
      stained positively for the presence of glycoproteins. From these results, it was
      concluded that C. lavaretus from Loch Eck possess both anatomical and biochemical
      adhesive mechanisms that have been undocumented in this species so far. 

PMID- 24580665
TI  - Molecular cloning and immune responsive expression of a ribonuclease III
      orthologue involved in RNA interference, dicer, in grass carp Ctenopharyngodon
      idella.
AB  - In this study, the dicer gene (designated as cidicer) was identified and
      characterized from grass carp Ctenopharyngodon idella. The complementary DNA
      (cDNA) of cidicer contained an open reading frame (ORF) of 5646 nucleotides (nts)
      encoding a putative protein of 1881 amino acids (aa). The deduced Dicer protein
      contained all known functional domains identified in other organisms. Tissue
      tropism analysis indicated that cidicer is abundantly expressed in brain, gill,
      head kidney, liver, spleen, heart, muscle and intestine. In the C. idella kidney
      (CIK) cells, messenger RNA (mRNA) expression of cidicer was significantly up
      regulated at 24 h (6.36-fold, P < 0.01) after grass carp reovirus (GCRV)
      infection, and its transcriptional expression level was also transiently induced
      to a high level (6.54-fold, P < 0.01) at 2 h post-stimulation of synthetic double
      stranded polyinosinic-polycytidylic potassium salt [poly(I:C)]. In vivo analysis
      further showed that the expression of cidicer mRNA in the liver was induced to a
      significantly high level at 12 h (8.46-fold, P < 0.01), and then dropped to
      normal level at 72 h post-challenge with GCRV. The transcriptional expression
      pattern of cidicer in the spleen tissue was similar to that of liver tissue upon
      GCRV challenge. These results collectively implied that the identified cidicer
      was an inducible gene responding to viral infection both in vitro and in vivo,
      and the data would shed light on the interaction between RNA interference (RNAi)
      antiviral pathway and aquareovirus infection. 

PMID- 24580666
TI  - Reduction in antipredator response detected between first and second generations
      of endangered juvenile Atlantic salmon Salmo salar in a captive breeding and
      rearing programme.
AB  - Behaviour trials determining antipredator response were conducted on first and
      second generation juveniles from a captive breeding and rearing programme for
      endangered Inner Bay of Fundy Atlantic salmon Salmo salar. Second generation
      captive fry displayed significantly higher levels of risk-taking behaviour before
      and after exposure to a simulated avian predator. Because the first and second
      generation fry were reared under the same environmental conditions and differed
      only in the number of generations spent in captivity, these results suggest that
      rapid genetic changes, possibly due to domestication selection, may have
      occurred. Antipredator response was also assessed in fully wild and highly
      domesticated experimental groups: wild fry displayed the greatest antipredator
      response and domesticated fry displayed the highest levels of risk-taking
      behaviour. These results add to the growing evidence documenting rapid genetic
      change in response to rearing in a captive environment. 

PMID- 24580667
TI  - High dietary arachidonic acid levels affect the process of eye migration and head
      shape in pseudoalbino Senegalese sole Solea senegalensis early juveniles.
AB  - The effect of high dietary levels of arachidonic acid (ARA) on the eye migration
      and cranial bone remodelling processes in Senegalese sole Solea senegalensis
      early juveniles (age: 50 days post hatch) was evaluated by means of geometric
      morphometric analysis and alizarin red staining of cranial skeletal elements. The
      incidence of normally pigmented fish fed the control diet was 99.1 +/- 0.3% (mean
      +/- s.e.), whereas it was only 18.7 +/- 7.5% for those fed high levels of ARA
      (ARA-H). The frequency of cranial deformities was significantly higher in fish
      fed ARA-H (95.1 +/- 1.5%) than in those fed the control diet (1.9 +/- 1.9%).
      Cranial deformities were significantly and negatively correlated with the
      incidence of normally pigmented animals (r2 = -0.88, P < 0.001, n = 16). Thus,
      fish displaying pigmentary disorders differed in the position of their eyes with
      regard to the vertebral column and mouth axes, and by the interocular distance
      and head height, which were shorter than in fish not displaying pigmentary
      disorders. In addition to changes in the positioning of both eyes, pseudoalbino
      fish showed some ARA-induced osteological differences for some of the skeletal
      elements from the splanchnocranium (e.g. right premaxillary, dentary, angular,
      lacrimal, ceratohyal and branchiostegal rays) and neurocranium (e.g. sphenotic,
      left lateral ethmoid and left frontal) by comparison to normally pigmented
      specimens. Pseudoalbino fish also had teeth in both lower and upper jaws. This is
      the first study in Pleuronectiformes that describes impaired metamorphic
      relocation of the ocular side eye, the right eye in the case of S. senegalensis,
      whereas the left eye migrated into the ocular side almost normally.

PMID- 24580668
TI  - Sexual dimorphism in scales of marbled flounder Pseudopleuronectes yokohamae
      (Pleuronectiformes: Pleuronectidae), with comments on the relevance to their
      spawning behaviour.
AB  - Variation of scales on the blind side of Pseudopleuronectes yokohamae in relation
      to sex, maturity and body size was examined. Immature males often have cycloid
      scales, while mature males have mostly ctenoid scales. Large females also often
      have ctenoid scales (but with fewer spines compared with males), and small
      females have mostly cycloid scales. The number of spines (ctenii) on the blind
      side scale increases with body size in both sexes, indicating an ontogenetic
      change in scale morphology. As P. yokohamae spawn demersal eggs with males
      positioning themselves above the females on the ocular side, it is hypothesized
      that ctenoid scales on the blind side in mature males function for maintaining
      contact with females during spawning. 

PMID- 24580669
TI  - Feeding strategy of juvenile (age-0+ year) Argentine hake Merluccius hubbsi in
      the Patagonian nursery ground.
AB  - Age-0+ year juvenile Argentine hake Merluccius hubbsi (60-150 mm total length,
      L(T)) from San Jorge Gulf, north Patagonian shelf region of the Argentine Sea,
      had an almost exclusively pelagic diet dominated by the hyperiid amphipod
      Themisto gaudichaudii and the euphausiid Euphausia lucens. This suggested that
      final settlement and permanent demersal habitat utilization might not, as
      previously reported, occur at earlier sizes (c. 20 mm L(T)). Their feeding
      strategy involves specialization at a population level towards both the main
      pelagic prey, indicating a narrow trophic niche. Novel data are provided which
      contribute to the growing body of information in relation to the age-0+ year
      transitional stage in demersal fishes and particularly to M. hubbsi recruitment
      in the Argentine Sea.

PMID- 24580670
TI  - Incomplete behavioural isolation and asymmetric female preference in darter
      sister species (Percidae: Etheostoma).
AB  - In this study, female preferences and behavioural isolation were estimated in a
      pair of allopatric sister species, Etheostoma duryi and Etheostoma flavum.
      Dichotomous mate preference trials were conducted to determine whether females
      prefer to associate with conspecific over heterospecific males and free-spawning
      assays were conducted to determine whether those preferences translated into
      behavioural isolation. Dichotomous mate choice trials revealed asymmetric female
      preference, as female E. flavum preferred conspecific males, whereas female E.
      duryi showed no preference. Free-spawning assays indicated that behavioural
      isolation remains incomplete between E. duryi and E. flavum (IB = 0.19). In
      addition to female mating preferences, male behaviour also appeared to influence
      mating outcomes as male E. flavum consistently courted conspecific females more
      often in free-spawning assays whereas male E. duryi did not. The data therefore
      suggest that despite marked divergence in male nuptial colour, divergence in
      female preferences between these species may not be sufficient to maintain
      species boundaries upon secondary contact. These results contrast with similar
      work in a sympatric darter species pair and may be explained by considering the
      contributions of reinforcement and differences in colour pattern as well as
      colour value. 

PMID- 24580671
TI  - Are zebrafish Danio rerio males better swimmers than females?
AB  - Swimming performance of zebrafish Danio rerio males and females initially reared
      in four different temperatures was assessed by measuring their relative critical
      swimming speed after acclimation to a common temperature. Males reared at 31
      degrees  C achieved higher swimming speeds than females reared at the same
      temperature. Morphometric measurements indicate differences in body shape between
      sexes that could account for the difference in swimming speed. 

PMID- 24580672
TI  - Scale-stacking in the live-bearer Belonesox belizanus (Poeciliidae).
AB  - An incidence of scale-stacking was found in a museum collection of Belonesox
      belizanus (Poeciliidae) from the Rio Tesechocan, Veracruz, Mexico. This
      phenomenon is thought to be unique to lepidophagous East African cichlids,
      although no studies have addressed the behaviour in any detail. This finding in
      B. belizanus, the first in Cyprinodontiformes, indicates Belonesox is able to
      manipulate scales into stacks in the buccal cavity. 

PMID- 24580673
TI  - A portable electro-immobilization and laparoscopy system for sex determination
      and gonadal biopsy in largemouth bass Micropterus salmoides.
AB  - A portable electro-immobilization and laparoscopy system is described that is
      suitable for sex determination, gonadal biopsy and immediate release of
      largemouth bass Micropterus salmoides. Continuous direct current at a power
      density of 52.2 uW cm-1 for 2 min was sufficient to immobilize fish for surgery,
      but induced a mild, transient hypokalaemia and hyperglycaemia. Insertion of a 4.8
      mm laparoscopic instrument set through the urogenital pore provided access to the
      gonads for examination and biopsy with mild tissue trauma.

PMID- 24580674
TI  - Blood lactate loads of redthroat emperor Lethrinus miniatus associated with
      angling stress and exhaustive exercise.
AB  - Baseline, post-angling and maximum attainable blood lactate concentrations were
      measured for the fishery species redthroat emperor Lethrinus miniatus to gain
      insight into the condition of fish released following c. 30 s angling and <45 s
      air exposure. Mean +/- S.D. baseline blood lactate was 1.5 +/- 0.6 mmol l-1,
      which increased and plateaued around 6 mmol l-1 at 15-30 min post-angling. These
      values were significantly lower than those obtained from fish maximally exhausted
      with a prolonged chase and air exposure protocol following capture (10.9 +/- 1.8
      mmol l-1), suggesting that L. miniatus is not maximally exhausted during standard
      angling practices.

PMID- 24580675
TI  - The first record of the slender sunfish Ranzania laevis from the Red Sea.
AB  - A female specimen of the slender sunfish Ranzania laevis of 600 mm total length
      was recorded for the first time from the Red Sea after being stranded on a
      shallow sandy bay at Hurghada beach (27 degrees  06' 16" N; 33 degrees  50' 01"
      E) on 13 May 2012. Ranzania laevis is believed to have migrated from the Indian
      Ocean as the nearest area where it was found is coastal waters of Oman. 

PMID- 24580676
TI  - Occurrence of age-0 year dwarf pikeperch Sander lucioperca in late summer--an
      overlooked phenomenon in reservoirs.
AB  - Late summer sampling of pelagic age-0 year fish communities in five Czech
      reservoirs and one Dutch reservoir revealed extremely small age-0 year pikeperch
      Sander lucioperca (mean 24 mm standard length, LS , minimum 13 mm LS ) alongside
      more normal-sized S. lucioperca that are found at the end of the first growing
      season (mean 50 mm LS ), resulting in two clearly size-separated cohorts.
      Reference to such small age-0 year S. lucioperca in lakes or reservoirs at this
      time of year and in such large numbers are almost absent the scientific
      literature, and the presence of these small S. lucioperca is contradictory to the
      common understanding of the reproductive biology of this species. This overlooked
      phenomenon may have a major effect on the population dynamics of this valuable
      species because of size-dependent winter mortality. 

PMID- 24580677
TI  - Calcium-activated chloride channels do not contribute to the odorant transduction
      current in the marine teleost Isacia conceptionis.
AB  - This study compared the contribution of the Ca2+-activated Cl- conductance to the
      electroolfactogram (EOG) evoked by different odorant classes between the marine
      Cabinza grunt Isacia conceptionis and rainbow trout Oncorhynchus mykiss. The Ca2+
      activated Cl- channel blocker niflumic acid significantly diminished odorant
      responses in O. mykiss, but had no effect on the EOG in I. conceptionis,
      supporting the notion that Ca2+-activated Cl- channels may not operate as odorant
      transduction current amplifiers in this marine teleost.

PMID- 24580680
TI  - Third-generation inhibitor for the renin-angiotensin system: Can it strongly
      protect against progression of hepatic fibrosis in non-alcoholic steatohepatitis?

PMID- 24580681
TI  - Case of cerebral lipiodol embolism after repeated transcatheter arterial
      chemoembolization of hepatocellular carcinoma.

PMID- 24580682
TI  - Confocal Raman investigation of diffusion processes in monolithic type
      transdermal drug delivery systems.
AB  - Release from a transdermal drug delivery system (TDDS) can either be controlled
      by diffusion in the adhesive, by diffusion processes in the stratum corneum of
      the skin or a combination of both. In this study, diffusion processes in
      monolithic type TDDS were investigated using confocal Raman microscopy. An
      acrylic adhesive (Duro-Tak 180-129a), a rubber adhesive (Duro-Tak H1540) and a
      silicone adhesive (BIO-PSA 7-4202) were used. Skin permeation of the model drug
      Paeonol from these adhesives was investigated. Release studies on porcine cadaver
      skin were carried out. Solubility of Paeonol in the different adhesives was
      measured. Diffusion coefficients of the drug in the TDDSs were calculated from
      confocal Raman depth scans, the diffusion coefficient in the stratum corneum was
      calculated using tape stripping. Solubility of Paeonol in the acrylic adhesive
      was the highest with 30 g/L among the tested systems. Paeonol had a solubility of
      6 and 9 g/L in the silicone and rubber based system. Diffusion coefficient rank
      order was BIO-PSA 7-4204 > Duro-Tak 180-129a > Duro-Tak H1540. Release on porcine
      cadaver skin from the silicone was the highest followed by the rubber and the
      acrylic adhesive. During release studies on porcine skin with Duro-Tak H1540 no
      concentration gradient of Paeonol could be monitored in the Raman depth profiles,
      whereas in the stratum corneum an apparent diffusion gradient was detectable.
      Solubility of a drug in the adhesive dominated the release properties, high
      diffusion coefficients of drugs in adhesives do not necessarily lead to high
      release rates from adhesives.

PMID- 24580679
TI  - A homolog of splicing factor SF1 is essential for development and is involved in
      the alternative splicing of pre-mRNA in Arabidopsis thaliana.
AB  - During initial spliceosome assembly, SF1 binds to intron branch points and
      interacts with U2 snRNP auxiliary factor 65 (U2AF65). Here, we present evidence
      indicating that AtSF1, the Arabidopsis SF1 homolog, interacts with AtU2AF65a and
      AtU2AF65b, the Arabidopsis U2AF65 homologs. A mutant allele of AtSF1 (At5g51300)
      that contains a T-DNA insertion conferred pleiotropic developmental defects,
      including early flowering and abnormal sensitivity to abscisic acid. An AtSF1
      promoter-driven GUS reporter assay showed that AtSF1 promoter activity was
      temporally and spatially altered, and that full AtSF1 promoter activity required
      a significant proportion of the coding region. DNA chip analyses showed that only
      a small proportion of the transcriptome was altered by more than twofold in
      either direction in the AtSF1 mutant. Expression of the mRNAs of many heat shock
      proteins was more than fourfold higher in the mutant strain; these mRNAs were
      among those whose expression was increased most in the mutant strain. An RT-PCR
      assay revealed an altered alternative splicing pattern for heat shock
      transcription factor HsfA2 (At2g26150) in the mutant; this altered splicing is
      probably responsible for the increased expression of the target genes induced by
      HsfA2. Altered alternative splicing patterns were also detected for the
      transcripts of other genes in the mutant strain. These results suggest that AtSF1
      has functional similarities to its yeast and metazoan counterparts. 

PMID- 24580683
TI  - Evaporative production of bright atomic solitons.
AB  - We describe a method of producing bright atomic solitons of 7Li through efficient
      radio frequency evaporation in a combined magnetic and optical trap. Solitons
      released in a magnetic waveguide propagate without dispersion, with lifetimes
      limited by two-body dipolar relaxation. We show how the method can be used to
      deterministically produce pairs of solitons.

PMID- 24580684
TI  - Bidirectional energy cascades and the origin of kinetic Alfvenic and whistler
      turbulence in the solar wind.
AB  - The observed steep kinetic scale turbulence spectrum in the solar wind raises the
      question of how that turbulence originates. Observations of keV energetic
      electrons during solar quiet time suggest them as a possible source of free
      energy to drive kinetic turbulence. Using particle-in-cell simulations, we
      explore how the free energy released by an electron two-stream instability drives
      Weibel-like electromagnetic waves that excite wave-wave interactions.
      Consequently, both kinetic Alfvenic and whistler turbulence are excited that
      evolve through inverse and forward magnetic energy cascades. 

PMID- 24580685
TI  - Probing dark energy with lensing magnification in photometric surveys.
AB  - I present an estimator for the angular cross correlation of two tracers of the
      cosmological large-scale structure that utilizes redshift information to isolate
      separate physical contributions. The estimator is derived by solving the Limber
      equation for a reweighting of the foreground tracer that nulls either clustering
      or lensing contributions to the cross correlation function. Applied to future
      photometric surveys, the estimator can enhance the measurement of gravitational
      lensing magnification effects to provide a competitive independent constraint on
      the dark energy equation of state. 

PMID- 24580688
TI  - One-dimensional alpha condensation of alpha-linear-chain states in 12C and 16O.
AB  - We present a new picture that the alpha-linear-chain structure for 12C and 16O
      has one-dimensional alpha condensate character. The wave functions of linear
      chain states that are described by superposing a large number of Brink wave
      functions have extremely large overlaps of nearly 100% with single Tohsaki
      Horiuchi-Schuck-Ropke wave functions, which were proposed to describe the alpha
      condensed "gaslike" states. Although this new picture is different from the
      conventional idea of the spatial localization of alpha clusters, the density
      distributions are shown to have localized alpha clusters due to the inter-alpha
      Pauli repulsion.

PMID- 24580689
TI  - Probing the symmetries of the Dirac Hamiltonian with axially deformed scalar and
      vector potentials by similarity renormalization group.
AB  - Symmetry is an important and basic topic in physics. The similarity
      renormalization group theory provides a novel view to study the symmetries hidden
      in the Dirac Hamiltonian, especially for the deformed system. Based on the
      similarity renormalization group theory, the contributions from the
      nonrelativistic term, the spin-orbit term, the dynamical term, the relativistic
      modification of kinetic energy, and the Darwin term are self-consistently
      extracted from a general Dirac Hamiltonian and, hence, we get an accurate
      description for their dependence on the deformation. Taking an axially deformed
      nucleus as an example, we find that the self-consistent description of the
      nonrelativistic term, spin-orbit term, and dynamical term is crucial for
      understanding the relativistic symmetries and their breaking in a deformed
      nuclear system. 

PMID- 24580690
TI  - Hyperfine structure in 229gTh3+ as a probe of the 229gTh-> 229mTh nuclear
      excitation energy.
AB  - We identify a potential means to extract the 229gTh-> 229mTh nuclear excitation
      energy from precision microwave spectroscopy of the 5F(5/2,7/2) hyperfine
      manifolds in the ion 229gTh3+. The hyperfine interaction mixes this ground fine
      structure doublet with states of the nuclear isomer, introducing small but
      observable shifts to the hyperfine sublevels. We demonstrate how accurate atomic
      structure calculations may be combined with the measurement of the hyperfine
      intervals to quantify the effects of this mixing. Further knowledge of the
      magnetic dipole decay rate of the isomer, as recently reported, allows an
      indirect determination of the nuclear excitation energy.

PMID- 24580691
TI  - Correlation dynamics during a slow interaction quench in a one-dimensional Bose
      gas.
AB  - We investigate the response of a one-dimensional Bose gas to a slow increase of
      its interaction strength. We focus on the rich dynamics of equal-time single
      particle correlations treating the Lieb-Liniger model within a bosonization
      approach and the Bose-Hubbard model using the time-dependent density-matrix
      renormalization group method. For short distances, correlations follow a power
      law with distance with an exponent given by the adiabatic approximation. In
      contrast, for long distances, correlations decay algebraically with an exponent
      understood within the sudden quench approximation. This long distance regime is
      separated from an intermediate distance one by a generalized Lieb-Robinson
      criterion. At long times, in this intermediate regime, bosonization predicts that
      single-particle correlations decay following a stretched exponential, an
      unconventional behavior. We develop here an intuitive understanding for the
      propagation of correlations, in terms of a generalized light cone, applicable to
      a large variety of systems and quench forms. 

PMID- 24580692
TI  - Rupture cascades in a discrete element model of a porous sedimentary rock.
AB  - We investigate the scaling properties of the sources of crackling noise in a
      fully dynamic numerical model of sedimentary rocks subject to uniaxial
      compression. The model is initiated by filling a cylindrical container with
      randomly sized spherical particles that are then connected by breakable beams.
      Loading at a constant strain rate the cohesive elements fail, and the resulting
      stress transfer produces sudden bursts of correlated failures, directly analogous
      to the sources of acoustic emissions in real experiments. The source size,
      energy, and duration can all be quantified for an individual event, and the
      population can be analyzed for its scaling properties, including the distribution
      of waiting times between consecutive events. Despite the nonstationary loading,
      the results are all characterized by power-law distributions over a broad range
      of scales in agreement with experiments. As failure is approached, temporal
      correlation of events emerges accompanied by spatial clustering. 

PMID- 24580693
TI  - Lattice thermal conductivity of Si(1-x)Ge(x) nanocomposites.
AB  - We calculate the lattice thermal conductivity in model Si(1-x)Ge(x)
      nanocomposites by molecular dynamics in a transient thermal conduction regime.
      Our simulations provide evidence that thermal transport depends only marginally
      on stoichiometry in the range 0.2<=x<=0.8, while it is deeply affected by the
      granulometry. In particular, we show that Si(1-x)Ge(x) nanocomposites have
      lattice thermal conductivity below the corresponding bulk alloy with the same
      stoichiometry. The main role in affecting thermal conduction is provided by grain
      boundaries, which largely affect vibrational modes with a long mean-free path.

PMID- 24580695
TI  - Capillary bridges between soft substrates.
AB  - A wetting droplet trapped in the thin gap between two elastic bodies will deflect
      the bodies towards one another. The deformation increases the total capillary
      adhesion force by increasing the contact radius and narrowing the gap height. For
      flat droplets, with a large ratio of radius to gap height, the Laplace pressure
      causes surface deformations that are orders of magnitude larger than those
      induced by a sessile droplet of the same radius. We present experiments,
      scalings, and closed-form solutions that describe the deformation. Using
      variational techniques, we also show that the problem exhibits a bifurcation,
      where the gap spontaneously closes due to an incremental increase in drop volume.

PMID- 24580694
TI  - Chemical and crystallographic characterization of the tip apex in scanning probe
      microscopy.
AB  - The apex atom of a W scanning probe tip reveals a nonspherical charge
      distribution as probed by a CO molecule bonded to a Cu(111) surface [Welker et
      al., Science 336, 444 (2012). Three high-symmetry images were observed and
      related to three low-index crystallographic directions of the W bcc crystal. Open
      questions remained, such as the detectability of a contamination of W tips by
      sample material (here Cu), and the applicability of the method to distinguish
      other atomic species. In this work, we investigate bulk Cu and Fe tips. In both
      cases, we can associate our data with the fcc (Cu) and bcc (Fe) crystal
      structures using a simple electrostatic model that is based on the partial
      filling of d orbitals.

PMID- 24580696
TI  - NMR study of the superconducting gap variation near the Mott transition in
      Cs3C60.
AB  - Former extensive studies of superconductivity in the A3C60 compounds, where A is
      an alkali metal, have led one to consider that Bardeen-Cooper-Schrieffer electron
      phonon pairing prevails in those compounds, though the incidence of electronic
      Coulomb repulsion has been highly debated. The discovery of two isomeric
      fulleride compounds Cs3C60 which exhibit a transition with pressure from a Mott
      insulator (MI) to a superconducting (SC) state clearly reopens that question.
      Using pressure (p) as a single control parameter of the C60 balls lattice
      spacing, one can now study the progressive evolution of the SC properties when
      the electronic correlations are increased towards the critical pressure p(c) of
      the Mott transition. We have used 13C and 133Cs NMR measurements on the cubic
      phase A15-Cs3C60 just above p(c)=5.0(3) kbar, where the SC transition temperature
      Tc displays a dome shape with decreasing cell volume. From the T dependence below
      T(c) of the nuclear spin lattice relaxation rate (T1)(-1) we determine the
      electronic excitations in the SC state, that is 2Delta, the gap value. The latter
      is found to be largely enhanced with respect to the Bardeen-Cooper-Schrieffer
      value established in the case of dense A3C60 compounds. It even increases
      slightly with decreasing p towards p(c), where T(c) decreases on the SC dome, so
      that 2Delta/k(B)T(c) increases regularly upon approaching the Mott transition.
      These results bring clear evidence that the increasing correlations near the Mott
      transition are not significantly detrimental to superconductivity. They rather
      suggest that repulsive electron interactions might even reinforce elecron-phonon
      superconductivity, being then partly responsible for the large T(c) values, as
      proposed by theoretical models taking the electronic correlations as a key
      ingredient.

PMID- 24580697
TI  - Non-Abelian gauge fields in photonic cavities and photonic superfluids.
AB  - We show that the TE-TM modes splitting and the structure anisotropy of a
      semiconductor microcavity combine into a non-Abelian gauge field for exciton
      polaritons or cavity photons. The field texture can be tuned simply by rotating
      the sample and ranges continuously from a Rashba to a monopolar field. In the
      noninteracting regime, the latter leads to remarkable focusing and conical
      diffraction effects. In the interacting regime, the spin-orbit coupling induces a
      breakdown of superfluidity. The spatially homogeneous flows become unstable and
      dynamically evolve into spin textured states, such as stripes or domain walls. 

PMID- 24580698
TI  - Metastable defect formation at microvoids identified as a source of light-induced
      degradation in a-Si:H.
AB  - Light-induced degradation of hydrogenated amorphous silicon (a-Si:H), known as
      the Staebler-Wronski effect, has been studied by time-domain pulsed electron
      paramagnetic resonance. Electron-spin echo relaxation measurements in the
      annealed and light-soaked state revealed two types of defects (termed type I and
      II), which can be discerned by their electron-spin echo relaxation. Type I
      exhibits a monoexponential decay related to indirect flip-flop processes between
      dipolar coupled electron spins in defect clusters, while the phase relaxation of
      type II is dominated by 1H nuclear spin dynamics and is indicative for isolated
      spins. We propose that defects are either located at internal surfaces of
      microvoids (type I) or are isolated and uniformly distributed in the bulk (type
      II). The concentration of both defect type I and II is significantly higher in
      the light-soaked state compared to the annealed state. Our results indicate that
      in addition to isolated defects, defects on internal surfaces of microvoids play
      a role in light-induced degradation of device-quality a-Si:H.

PMID- 24580686
TI  - Spectral measurement of electron antineutrino oscillation amplitude and frequency
      at Daya Bay.
AB  - A measurement of the energy dependence of antineutrino disappearance at the Daya
      Bay reactor neutrino experiment is reported. Electron antineutrinos (nu-(e)) from
      six 2.9  GW(th) reactors were detected with six detectors deployed in two near
      (effective baselines 512 and 561 m) and one far (1579 m) underground experimental
      halls. Using 217 days of data, 41 589 (203 809 and 92 912) antineutrino
      candidates were detected in the far hall (near halls). An improved measurement of
      the oscillation amplitude sin(2)2theta(13)=0.090(-0.009)(+0.008) and the first
      direct measurement of the nu-(e) mass-squared difference |Deltam(ee)2|=(2.59(
      0.20)(+0.19))*10(-3)  eV2 is obtained using the observed nu-(e) rates and energy
      spectra in a three-neutrino framework. This value of |Deltam(ee)2| is consistent
      with |Deltam(MUMU)2| measured by muon neutrino disappearance, supporting the
      three-flavor oscillation model.

PMID- 24580699
TI  - Extrinsic spin Hall effect induced by resonant skew scattering in graphene.
AB  - We show that the extrinsic spin Hall effect can be engineered in monolayer
      graphene by decoration with small doses of adatoms, molecules, or nanoparticles
      originating local spin-orbit perturbations. The analysis of the single impurity
      scattering problem shows that intrinsic and Rashba spin-orbit local couplings
      enhance the spin Hall effect via skew scattering of charge carriers in the
      resonant regime. The solution of the transport equations for a random ensemble of
      spin-orbit impurities reveals that giant spin Hall currents are within the reach
      of the current state of the art in device fabrication. The spin Hall effect is
      robust with respect to thermal fluctuations and disorder averaging. 

PMID- 24580700
TI  - Possible evidence for helical nuclear spin order in GaAs quantum wires.
AB  - We present transport measurements of cleaved edge overgrowth GaAs quantum wires.
      The conductance of the first mode reaches 2e(2)/h at high temperatures T?10 K, as
      expected. As T is lowered, the conductance is gradually reduced to 1e(2)/h,
      becoming T independent at T?0.1 K, while the device cools far below 0.1 K. This
      behavior is seen in several wires, is independent of density, and not altered by
      moderate magnetic fields B. The conductance reduction by a factor of 2 suggests
      lifting of the electron spin degeneracy in the absence of B. Our results are
      consistent with theoretical predictions for helical nuclear magnetism in the
      Luttinger liquid regime.

PMID- 24580701
TI  - Spin-dependent electron scattering at graphene edges on Ni(111).
AB  - We investigate the scattering of surface electrons by the edges of graphene
      islands grown on Ni(111). By combining local tunneling spectroscopy and ab initio
      electronic structure calculations we find that the hybridization between graphene
      and Ni states results in strongly reflecting graphene edges. Quantum interference
      patterns formed around the islands reveal a spin-dependent scattering of the
      Shockley bands of Ni, which we attribute to their distinct coupling to bulk
      states. Moreover, we find a strong dependence of the scattering amplitude on the
      atomic structure of the edges, depending on the orbital character and energy of
      the surface states. 

PMID- 24580702
TI  - Metal oxide resistive switching: evolution of the density of states across the
      metal-insulator transition.
AB  - We report the study of gold-SrTiO3 (STO)-gold memristors where the doping
      concentration in STO can be fine-tuned through electric field migration of oxygen
      vacancies. In this tunnel junction device, the evolution of the density of states
      (DOS) can be followed continuously across the metal-insulator transition (MIT).
      At very low dopant concentration, the junction displays characteristic signatures
      of discrete dopant levels. As the dopant concentration increases, the
      semiconductor band gap fills in but a soft Coulomb gap remains. At even higher
      doping, a transition to a metallic state occurs where the DOS at the Fermi level
      becomes finite and Altshuler-Aronov corrections to the DOS are observed. At the
      critical point of the MIT, the DOS scales linearly with energy
      N(epsilon)~epsilon, the possible signature of multifractality.

PMID- 24580703
TI  - "Smile" gap in the density of states of a cavity between superconductors.
AB  - The density of Andreev levels in a normal metal (N) in contact with two
      superconductors (S) is known to exhibit an induced minigap related to the inverse
      dwell time. We predict a small secondary gap just below the superconducting gap
      edge-a feature that has been overlooked so far in numerous microscopic studies of
      the density of states in S-N-S structures. In a generic structure with N being a
      chaotic cavity, the secondary gap is the widest at zero phase bias. It closes at
      some finite phase bias, forming the shape of a "smile". Asymmetric couplings give
      even richer gap structures near the phase difference pi. All the features found
      should be amendable to experimental detection in high-resolution low-temperature
      tunneling spectroscopy. 

PMID- 24580704
TI  - Multiband superconductivity with unexpected deficiency of nodal quasiparticles in
      CeCu2Si2.
AB  - Superconductivity in the heavy-fermion compound CeCu2Si2 is a prototypical
      example of Cooper pairs formed by strongly correlated electrons. For more than 30
      years, it has been believed to arise from nodal d-wave pairing mediated by a
      magnetic glue. Here, we report a detailed study of the specific heat and
      magnetization at low temperatures for a high-quality single crystal.
      Unexpectedly, the specific-heat measurements exhibit exponential decay with a two
      gap feature in its temperature dependence, along with a linear dependence as a
      function of magnetic field and the absence of oscillations in the field angle,
      reminiscent of multiband full-gap superconductivity. In addition, we find
      anomalous behavior at high fields, attributed to a strong Pauli paramagnetic
      effect. A low quasiparticle density of states at low energies with a multiband
      Fermi-surface topology would open a new door into electron pairing in CeCu2Si2. 

PMID- 24580705
TI  - Exactly solvable counting statistics in open weakly coupled interacting spin
      systems.
AB  - We study the full counting statistics for interacting quantum many-body spin
      systems weakly coupled to the environment. In the leading order in the system
      bath coupling, we derive exact spin current statistics for a large class of
      parity symmetric spin-1/2 systems driven by a pair of Markovian baths with local
      coupling operators. Interestingly, in this class of systems the leading-order
      current statistics are universal and do not depend on details of the Hamiltonian.
      Furthermore, in the specific case of a symmetrically boundary driven anisotropic
      Heisenberg (XXZ) spin-1/2 chain, we explicitly derive the third-order nonlinear
      corrections to the current statistics. 

PMID- 24580706
TI  - Spirals and Skyrmions in two dimensional oxide heterostructures.
AB  - We construct the general free energy governing long-wavelength magnetism in two
      dimensional oxide heterostructures, which applies irrespective of the microscopic
      mechanism for magnetism. This leads, in the relevant regime of weak but non
      negligible spin-orbit coupling, to a rich phase diagram containing in-plane
      ferromagnetic, spiral, cone, and Skyrmion lattice phases, as well as a nematic
      state stabilized by thermal fluctuations. 

PMID- 24580707
TI  - Metal-insulator photocathode heterojunction for directed electron emission.
AB  - We use angle-resolved photoemission under ultraviolet laser excitation to
      demonstrate that the electron emission properties of Ag(001) can be markedly
      enhanced and redirected along the surface normal by the deposition of a few
      monolayers of epitaxial MgO. We observe new low-binding energy states with small
      spreads in their surface parallel momenta as a result of MgO/Ag(001) interface
      formation. Under 4.66 eV laser excitation, the quantum efficiency of MgO/Ag(001)
      is a factor of 7 greater than that of clean Ag(001), revealing the utility of
      such heterojunctions as advanced photocathodes.

PMID- 24580687
TI  - Observation of electron neutrino appearance in a muon neutrino beam.
AB  - The T2K experiment has observed electron neutrino appearance in a muon neutrino
      beam produced 295 km from the Super-Kamiokande detector with a peak energy of 0.6
      GeV. A total of 28 electron neutrino events were detected with an energy
      distribution consistent with an appearance signal, corresponding to a
      significance of 7.3sigma when compared to 4.92+/-0.55 expected background events.
      In the Pontecorvo-Maki-Nakagawa-Sakata mixing model, the electron neutrino
      appearance signal depends on several parameters including three mixing angles
      theta12, theta23, theta13, a mass difference Deltam(32)(2) and a CP violating
      phase delta(CP). In this neutrino oscillation scenario, assuming
      |Deltam(32)(2)|=2.4*10(-3)  eV(2), sin(2)theta(23)=0.5, and Deltam322>0
      (Deltam(32)(2)<0), a best-fit value of sin(2)2theta(13)=0.140(-0.032)(+0.038)
      (0.170(-0.037)(+0.045)) is obtained at delta(CP)=0. When combining the result
      with the current best knowledge of oscillation parameters including the world
      average value of theta(13) from reactor experiments, some values of delta(CP) are
      disfavored at the 90% C.L.

PMID- 24580708
TI  - Statistical mechanics model for the dynamics of collective epigenetic histone
      modification.
AB  - Epigenetic histone modifications play an important role in the maintenance of
      different cell phenotypes. The exact molecular mechanism for inheritance of the
      modification patterns over cell generations remains elusive. We construct a Potts
      type model based on experimentally observed nearest-neighbor enzyme lateral
      interactions and nucleosome covalent modification state biased enzyme
      recruitment. The model can lead to effective nonlocal interactions among
      nucleosomes suggested in previous theoretical studies, and epigenetic memory is
      robustly inheritable against stochastic cellular processes. 

PMID- 24580710
TI  - Shapes of a suspended curly hair.
AB  - We investigate how natural curvature affects the configuration of a thin elastic
      rod suspended under its own weight, as when a single strand of hair hangs under
      gravity. We combine precision desktop experiments, numerics, and theoretical
      analysis to explore the equilibrium shapes set by the coupled effects of
      elasticity, natural curvature, nonlinear geometry, and gravity. A phase diagram
      is constructed in terms of the control parameters of the system, namely the
      dimensionless curvature and weight, where we identify three distinct regions:
      planar curls, localized helices, and global helices. We analyze the stability of
      planar configurations, and describe the localization of helical patterns for long
      rods, near their free end. The observed shapes and their associated phase
      boundaries are then rationalized based on the underlying physical ingredients. 

PMID- 24580709
TI  - Lipid membranes as solvents for carbon nanoparticles.
AB  - Fullerene is scarcely soluble in most solvents, including alkanes. Yet, it has
      been shown that C60 dissolves in lipid bilayers, whose interior is chemically
      identical to alkanes. Here, we use molecular simulations to explain why lipid
      bilayers are better than alkanes at dissolving fullerene clusters. Fullerene
      aggregation is driven by entropy, but enthalpic contributions determine the
      difference between alkanes and bilayers. Surprisingly, confinement and chain
      alignment in the bilayer do not affect fullerene aggregation, while solvent
      density and the perturbation of solvent-solvent interactions are key factors. 

PMID- 24580711
TI  - DNA flexibility on short length scales probed by atomic force microscopy.
AB  - Unusually high bending flexibility has been recently reported for DNA on short
      length scales. We use atomic force microscopy (AFM) in solution to obtain a
      direct estimate of DNA bending statistics for scales down to one helical turn. It
      appears that DNA behaves as a Gaussian chain and is well described by the
      wormlike chain model at length scales beyond 3 helical turns (10.5 nm). Below
      this threshold, the AFM data exhibit growing noise because of experimental
      limitations. This noise may hide small deviations from the Gaussian behavior, but
      they can hardly be significant.

PMID- 24580713
TI  - Emergent cometlike swarming of optically driven thermally active colloids.
AB  - We propose a simple system of optically driven colloids that convert light into
      heat and move in response to self-generated and collectively generated thermal
      gradients. We show that the system exhibits self-organization into a moving
      cometlike swarm and characterize the structure and response of the swarm to a
      light-intensity-dependent external tuning parameter. We observe many interesting
      features in this nonequilibrium system including circulation and evaporation,
      intensity-dependent shape, density and temperature fluctuations, and ejection of
      hot colloids from the swarm tip. 

PMID- 24580712
TI  - Self-assembly of catalytically active colloidal molecules: tailoring activity
      through surface chemistry.
AB  - A heterogeneous and dilute suspension of catalytically active colloids is studied
      as a nonequilibrium analogue of ionic systems, which has the remarkable feature
      of action-reaction symmetry breaking. Symmetrically coated colloids are found to
      join up to form self-assembled molecules that could be inert or have spontaneous
      activity in the form of net translational velocity and spin depending on their
      symmetry properties and their constituents. The type of activity can be adjusted
      by changing the surface chemistry and ambient variables that control the surface
      reactions and the phoretic drift. 

PMID- 24580714
TI  - Quantized contact angles in the dewetting of a structured liquid.
AB  - We investigate the dewetting of a disordered melt of diblock copolymer from an
      ordered residual wetting layer. In contrast to simple liquids where the wetting
      layer has a fixed thickness and the droplets exhibit a single unique contact
      angle with the substrate, we find that structured liquids of diblock copolymer
      exhibit a discrete series of wetting layer thicknesses each producing a different
      contact angle. These quantized contact angles arise because the substrate and air
      surfaces each induce a gradient of lamellar order in the wetting layer. The
      interaction between the two surface profiles creates an effective interface
      potential that oscillates with film thickness, thus, producing a sequence of
      local minimums. The wetting layer thicknesses and corresponding contact angles
      are a direct measure of the positions and depths of these minimums. Self
      consistent field theory is shown to provide qualitative agreement with the
      experiment. 

PMID- 24580715
TI  - Solid-solid transition in Landau-Levich flow with soft-jammed systems.
AB  - We study the Landau-Levich problem, i.e., withdrawal of a plate from a bath of
      fluid, in the case of a soft-jammed system, which involves a transition from a
      solid bath to a solid layer stuck on the plate. We show that this solid-solid
      transition is prepared inside the bath before the emersion from the fluid,
      through the existence of a uniform (boundary) layer in the liquid regime along
      the plate. This layer controls the original characteristics of the (solid) coated
      layer, whose thickness is almost independent of the velocity but proportional to
      the material yield stress. 

PMID- 24580716
TI  - Review of methods for the catalytic hydrogenation of carboxamides.

PMID- 24580717
TI  - Dual role of C/EBPalpha as an activator and repressor of Galphai2 gene
      transcription.
AB  - The G-protein Galphai2 mediates signaling in a variety of processes. Induced
      expression of Galphai2 by butyrate and various transcription factors has been
      established, but transcriptional suppression has not previously been explored.
      Using HepG2 and K562 cells in culture, we show here that whereas both C/EBPalpha
      and C/EBPbeta induced transcription from the Galphai2 gene promoter, C/EBPalpha,
      but not C/EBPbeta, inhibited butyrate-induced Galphai2 expression. Because the
      transcriptional effect of butyrate on this gene promoter is largely mediated by
      the transcription factor Sp1, we investigated whether C/EBPalpha influenced Sp1
      induced Galphai2 gene transcription. Binding of C/EBPalpha to a C/EBP response
      element in Galphai2 gene promoter inhibited Sp1-induced promoter activity. ChIP
      analysis showed decreased butyrate-induced recruitment of Sp1 to the Galphai2
      gene promoter in response to C/EBPalpha treatment. Incubating cells with acetate
      or transfecting them with expression plasmid for either the acetyltransferase
      p300 or CREB-binding protein (CBP) reversed the antagonistic effect of C/EBPalpha
      on Sp1-dependent gene transcription, suggesting that the mechanistic basis for
      the antagonism is related to the squelching of co-activator acetyltransferase(s)
      by C/EBPalpha or the acetylation of Sp1 and/or C/EBPalpha. This work reveals that
      C/EBPalpha plays a dual role as an activator and as a repressor of Galphai2 gene
      transcription. 

PMID- 24580718
TI  - The tortuous journey of introducing the nurse practitioner as a new member of the
      healthcare team: a meta-synthesis.
AB  - The aim of this study was to explore the obstacles to and the opportunities for
      achieving optimal interprofessional team collaboration with the introduction of
      the nurse practitioner (NP). A team approach can contribute importantly to
      sustainable and safe patient care, and NPs have been added to the healthcare team
      in many countries. Following the international trend towards the development of
      the acute care NP, the role has recently been initiated in surgical care in
      Sweden. The introduction of an advanced nursing role into existing organisations
      raises questions about how the role will be developed and what its effects will
      be on collaboration between the different professions. We conducted a systematic
      review of qualitative studies using the meta-ethnographic approach developed by
      Noblit and Hare. Literature in the field of nursing was searched on PubMed and
      CINAHL, and empirical qualitative studies from outpatient and inpatient care in
      seven countries were included. The studies were appraised according to national
      guidelines and templates and were analysed and synthesised according to the meta
      ethnographic approach. A total of 26 studies were included in the synthesis. The
      analysis revealed four themes: (i) a threat to professional boundaries, (ii) a
      resource for the team, (iii) the quest for autonomy and control, and (iv)
      necessary properties of a developing interprofessional collaboration. Based on
      these themes, the synthesis was created and presented as a metaphorical journey.
      The implementation of a new nursing role in a traditional healthcare team is a
      complex process influenced by many factors and can be described as "a tortuous
      journey towards a partially unknown destination". The synthesised obstacles and
      opportunities drawn from international studies may help healthcare organisations
      and new NPs prepare for, and optimise, the implementation of a new nursing role. 

PMID- 24580719
TI  - HIV nucleoside reverse transcriptase inhibitors efavirenz and tenofovir change
      the growth and differentiation of primary gingival epithelium.
AB  - OBJECTIVES: An increasing number of HIV-infected patients are combating HIV
      infection through the use of antiretroviral drugs, including reverse
      transcriptase inhibitors. Oral complications associated with these drugs are
      becoming a mounting cause for concern. In our previous studies, both protease
      inhibitors and reverse transcriptase inhibitors have been shown to change the
      proliferation and differentiation state of oral tissues. This study examined the
      effect of a nonnucleoside and a nucleoside reverse transcriptase inhibitor on the
      growth and differentiation of gingival epithelium. METHODS: Organotypic (raft)
      cultures of gingival keratinocytes were treated with a range of efavirenz and
      tenofovir concentrations. Raft cultures were immunohistochemically analysed to
      determine the effect of these drugs on the expression of key differentiation and
      proliferation markers, including cytokeratins and proliferating cell nuclear
      antigen (PCNA). RESULTS: These drugs dramatically changed the proliferation and
      differentiation state of gingival tissues when they were present throughout the
      growth period of the raft tissue as well as when drugs were added to established
      tissue on day 8. Treatment with the drugs increased the expression of cytokeratin
      10 and PCNA and, conversely, decreased expression of cytokeratin 5, involucrin
      and cytokeratin 6. Gingival tissue exhibited increased proliferation in the
      suprabasal layers, increased fragility, and an inability to heal itself.
      CONCLUSIONS: Our results suggest that efavirenz and tenofovir treatments, even
      when applied in low concentrations for short periods of time, deregulated the
      cell cycle/proliferation and differentiation pathways, resulting in abnormal
      epithelial repair and proliferation. Our system could be developed as a potential
      model for studying the effects of HIV and highly active antiretroviral therapy
      (HAART) in vitro.

PMID- 24580720
TI  - Plant mating systems affect adaptive plasticity in response to herbivory.
AB  - The fitness consequences of mating system variation (e.g. inbreeding) have been
      studied for at least 200 years, yet the ecological consequences of this variation
      remain poorly understood. Most plants are capable of inbreeding, and also exhibit
      a remarkable suite of adaptive phenotypic responses to ecological stresses such
      as herbivory. We tested the consequences of experimental inbreeding on phenotypic
      plasticity in resistance and growth (tolerance) traits in Solanum carolinense
      (Solanaceae). Inbreeding reduced the ability of plants to up-regulate resistance
      traits following damage. Moreover, inbreeding disrupted growth trait responses to
      damage, indicating the presence of deleterious mutations at loci regulating
      growth under stress. Production of the phytohormones abscisic and indole acetic
      acid, and wounding-induced up-regulation of the defence signalling phytohormone
      jasmonic acid were all significantly reduced under inbreeding, indicating a
      phytohormonal basis for inbreeding effects on growth and defence trait
      regulation. We conclude that the plasticity of induced responses is negatively
      affected by inbreeding, with implications for fragmented populations facing mate
      limitation and stress as a consequence of environmental change.

PMID- 24580722
TI  - Boosting healthy heart employer-sponsored health dissemination efforts:
      identification and information-sharing intentions.
AB  - Health information dissemination options have expanded to include workplaces and
      employer-sponsored efforts. This study focuses on a core relational concept found
      in workplaces, organizational identification-the feeling of belongingness-and the
      impact of partnering with employers and health clinics in health information
      dissemination. We use social-identity theory and multiple identification to test
      our predictions from a sample of working adults representing more than 100
      different employers. We found that when people strongly identify with their
      employer, they have increased health behavioral intentions and they intend to
      talk about the health information with coworkers. The significant models explain
      more than 50% and 30% of the variance in these two outcomes. The experimental
      results examining single and multiple organizational sources revealed no
      differences on any outcomes. These findings offer a contribution to health
      information dissemination research by articulating how identification with an
      employer functions to affect behavioral intentions. 

PMID- 24580721
TI  - Headstrong intervention for pediatric migraine headache: a randomized clinical
      trial.
AB  - BACKGROUND: The purpose of this study was to evaluate the efficacy of a self
      guided CD-ROM program ("Headstrong") containing cognitive-behavioral self
      management strategies versus an educational CD-ROM program for treating
      headaches, headache-related disability, and quality of life. METHODS:
      Participants were 35 children ages 7-12 years with migraine recruited from one
      university medical center and two children's hospital headache clinics.
      Participants were randomly assigned to complete the Headstrong or educational
      control CD-ROM program over a 4-week period. Data on headache frequency,
      duration, and severity, migraine-related disability, and quality of life (QOL)
      were obtained at baseline, post-intervention, and 3-months post-intervention.
      RESULTS: At post-intervention, Headstrong resulted in lower severity (on a 10
      point scale) than the control group by child report (5.06 +/- 1.50 SD vs. 6.25 +/
      1.92 SD, p = 0.03, ES = 0.7). At 3-months post-intervention, parents reported
      less migraine-related disability (on the PedMIDAS) in the Headstrong group
      compared to the control group (1.36 +/- 2.06 SD vs. 5.18 +/- 6.40 SD; p = 0.04,
      ES = 0.8). There were no other group differences at post treatment or at 3-months
      post-intervention. CONCLUSIONS: When compared to an educational control,
      Headstrong resulted in lower pain severity at post-treatment and less migraine
      related disability at 3-months post-intervention, by child and parent report
      respectively. Headache frequency and quality of life did not change more for
      Headstrong versus control. Additional research is needed on the Headstrong
      Program to increase its efficacy and to test it with a larger sample recruited
      from multiple centers simultaneously.

PMID- 24580724
TI  - Health related quality of life in patients in dialysis after renal graft loss and
      effect of gender.
AB  - BACKGROUND: An increasing number of dialysis patients have returned to dialysis
      after renal graft loss, and the transition in disease state could likely be
      associated with reduced health related quality of life (HRQOL). Furthermore,
      gender differences in HRQOL have been observed in dialysis and kidney
      transplanted patients, but whether transition in disease state affects HRQOL
      differently in respect to gender is not known. The aims of this study were to
      compare HRQOL in dialysis patients with graft loss to transplant naive dialysis
      patients, and to explore possible gender differences. METHODS: In a cross
      sectional study, HRQOL was measured in 301 prevalent dialysis patients using the
      Kidney Disease and Quality of Life Short Form version 1.3. Adjusted comparisons
      were made between dialysis patients with previous graft loss and the transplant
      naive patients. Multiple linear regression analyses were performed with HRQOL as
      outcome variables. Interaction analyses using product terms were performed
      between gender and graft loss. HRQOL was analysed separately in both genders.
      RESULTS: Patients with renal graft loss (n = 50) did not experience lower HRQOL
      than transplant naive patients after multiple adjustments. Among patients with
      graft loss, women (n = 23) reported lower HRQOL than men (n = 27) in the items
      physical function (40 vs. 80, p = 0.006), and effect of kidney disease (49 vs.
      67, p = 0.017). Women with graft loss reported impaired kidney-specific HRQOL
      compared to transplant naive women (n = 79) in the items effect of kidney disease
      (50 vs. 72, p = 0.002) and cognitive function (80 vs. 93, p = 0.006), and this
      observation persisted after multiple adjustments. Such differences were not
      apparent in the male counterparts. CONCLUSIONS: Patients who resumed dialysis
      after renal graft loss did not have lower HRQOL than dialysis patients not
      previously transplanted. However, losing graft function was associated with
      reduced HRQOL in females, and important interactions were identified between
      graft loss and gender. This needs to be further explored in prospective studies.

PMID- 24580439
TI  - Search for dark matter in events with a hadronically decaying W or Z boson and
      missing transverse momentum in pp collisions at ?s=8  TeV with the ATLAS
      detector.
AB  - A search is presented for dark matter pair production in association with a W or
      Z boson in pp collisions representing 20.3  fb(-1) of integrated luminosity at
      ?s=8  TeV using data recorded with the ATLAS detector at the Large Hadron
      Collider. Events with a hadronic jet with the jet mass consistent with a W or Z
      boson, and with large missing transverse momentum are analyzed. The data are
      consistent with the standard model expectations. Limits are set on the mass scale
      in effective field theories that describe the interaction of dark matter and
      standard model particles, and on the cross section of Higgs production and decay
      to invisible particles. In addition, cross section limits on the anomalous
      production of W or Z bosons with large missing transverse momentum are set in two
      fiducial regions.

PMID- 24580723
TI  - Routine angiography in survivors of out of hospital cardiac arrest with return of
      spontaneous circulation: a single site registry.
AB  - BACKGROUND: Coronary revascularization in resuscitated out of hospital cardiac
      arrest (OOHCA) patients has been associated with improved survival. METHODS: This
      was a retrospective review of patients with OOHCA between 01/07/2007 and
      31/03/2009 surviving to hospital admission. Cardiac risk factors, demographics,
      treatment times, electrocardiogram (ECG), angiographic findings and in-hospital
      outcomes were recorded. RESULTS: Of the 78 patients, 63 underwent coronary
      angiography. Traditional cardiac risk factors were common in this group. Chest
      pain occurred in 33.3% pre-arrest, 59.0% were initially treated at a peripheral
      hospital, 83.3% had documented ventricular tachycardia or ventricular
      fibrillation, 55.1% had specific ECG changes, 65.4% had acute myocardial
      infarction (AMI) as the cause of OOHCA and the majority had multi-vessel disease.
      ST elevation strongly predicted AMI. The in-hospital survival was 67.9% with
      neurological deficit in 13.2% of survivors. The group of patients who had an
      angiogram were more likely to have AMI as a cause of cardiac arrest (71.4% vs
      40.0%, p = 0.01) and more likely to have survived to discharge (74.6% vs 40.0%, p
      < 0.01). Poor outcome was associated with older age, cardiogenic shock, longer
      transfer times, diabetes, renal impairment and a long duration to return of
      spontaneous circulation. CONCLUSIONS: Acute myocardial infarction was the
      commonest cause of OOHCA and a high rate of survival to discharge was seen with a
      strategy of routine angiography and revascularization.

PMID- 24580725
TI  - Liver antioxidant stores protect the brain from electromagnetic radiation (900
      and 1800 MHz)-induced oxidative stress in rats during pregnancy and the
      development of offspring.
AB  - OBJECTIVES: The present study determined the effects of mobile phone (900 and
      1800 MHz)-induced electromagnetic radiation (EMR) exposure on oxidative stress in
      the brain and liver as well as the element levels in growing rats from pregnancy
      to 6 weeks of age. METHODS: Thirty-two rats and their offspring were equally
      divided into three different groups: the control, 900 MHz, and 1800 MHz groups.
      The 900 MHz and 1800 MHz groups were exposed to EMR for 60 min/d during pregnancy
      and neonatal development. At the 4th, 5th, and 6th weeks of the experiment, brain
      samples were obtained. RESULTS: Brain and liver glutathione peroxidase
      activities, as well as liver vitamin A and beta-carotene concentrations decreased
      in the EMR groups, although brain iron, vitamin A, and beta-carotene
      concentrations increased in the EMR groups. In the 6th week, selenium
      concentrations in the brain decreased in the EMR groups. There were no
      statistically significant differences in glutathione, vitamin E, chromium,
      copper, magnesium, manganese, and zinc concentrations between the three groups.
      CONCLUSION: EMR-induced oxidative stress in the brain and liver was reduced
      during the development of offspring. Mobile phone-induced EMR could be considered
      as a cause of oxidative brain and liver injury in growing rats.

PMID- 24580726
TI  - The genome and life-stage specific transcriptomes of Globodera pallida elucidate
      key aspects of plant parasitism by a cyst nematode.
AB  - BACKGROUND: Globodera pallida is a devastating pathogen of potato crops, making
      it one of the most economically important plant parasitic nematodes. It is also
      an important model for the biology of cyst nematodes. Cyst nematodes and root
      knot nematodes are the two most important plant parasitic nematode groups and
      together represent a global threat to food security. RESULTS: We present the
      complete genome sequence of G. pallida, together with transcriptomic data from
      most of the nematode life cycle, particularly focusing on the life cycle stages
      involved in root invasion and establishment of the biotrophic feeding site.
      Despite the relatively close phylogenetic relationship with root-knot nematodes,
      we describe a very different gene family content between the two groups and in
      particular extensive differences in the repertoire of effectors, including an
      enormous expansion of the SPRY domain protein family in G. pallida, which
      includes the SPRYSEC family of effectors. This highlights the distinct biology of
      cyst nematodes compared to the root-knot nematodes that were, until now, the only
      sedentary plant parasitic nematodes for which genome information was available.
      We also present in-depth descriptions of the repertoires of other genes likely to
      be important in understanding the unique biology of cyst nematodes and of
      potential drug targets and other targets for their control. CONCLUSIONS: The data
      and analyses we present will be central in exploiting post-genomic approaches in
      the development of much-needed novel strategies for the control of G. pallida and
      related pathogens.

PMID- 24580728
TI  - Prompted awareness and use of Eating Well with Canada's Food Guide: a population
      based study.
AB  - BACKGROUND: Little is known about the awareness of Canada's Food Guide (CFG). The
      present study aimed to report the general and specific awareness of CFG
      recommendations among adults in Alberta, Canada. METHODS: For this cross
      sectional study, respondents (aged >18 years) from randomly selected households
      completed a telephone survey. Questions pertaining to CFG, physical activity, and
      vegetable and fruit consumption were included. Logistic regression determined
      associations between demographic characteristics and awareness of CFG. RESULTS:
      Thousand two hundred and ten Albertans (50% female, mean age 50.5 years)
      responded. Most [86.5%; 95% confidence interval (CI) = 84.6-88.4] indicated being
      generally aware of CFG when prompted and 82.5% were aware of specific CFG
      recommendations. There were no differences in age between those generally aware
      and unaware of CFG. Female sex [odds ratio (OR) = 3.6; 95%CI = 24-5.4], Caucasian
      ethnicity (OR = 3.7; 95% CI = 2.3-5.8), income >= Canadian $100 000 per annum (OR
      = 1.6; 95% CI = 1.1-2.3), reporting >=5 vegetables and fruit per day (OR = 2.1;
      95% CI = 1.4-3.2), exceeding recommended levels for physical activity (OR = 2.0;
      95% CI = 1.3-2.9) and perception of current weight as healthy (OR = 1.8; 95% CI =
      1.2-2.8) were associated with an awareness of CFG. CONCLUSIONS: Sex, ethnicity
      and income were associated with general awareness of CFG. Future studies could
      explore the relationship between awareness and other health-related behaviours.

PMID- 24580735
TI  - Program for the 2014 Annual Meeting of the American Society of Pediatric
      Neurosurgeons.

PMID- 24580727
TI  - Keap1-Nrf2 system regulates cell fate determination of hematopoietic stem cells.
AB  - Nrf2 is a major transcriptional activator of cytoprotective genes against
      oxidative/electrophilic stress, and Keap1 negatively regulates Nrf2. Emerging
      works have also suggested a role for Nrf2 as a regulator of differentiation in
      various cells, but the contribution of Nrf2 to the differentiation of
      hematopoietic stem cells (HSCs) remains elusive. Clarifying this point is
      important to understand Nrf2 functions in the development and/or resolution of
      inflammation. Here, we established two transgenic reporter mouse lines that
      allowed us to examine Nrf2 expression precisely in HSCs. Nrf2 was abundantly
      transcribed in HSCs, but its activity was maintained at low levels due to the
      Keap1-mediated degradation of Nrf2 protein. When we characterized Keap1-deficient
      mice, their bone marrow cells showed enhanced granulocyte-monocyte
      differentiation at the expense of erythroid and lymphoid differentiation.
      Importantly, Keap1-null HSCs showed lower expression of erythroid and lymphoid
      genes than did control HSCs, suggesting granulocyte-monocyte lineage priming in
      Keap1-null HSCs. This abnormal lineage commitment was restored by a concomitant
      deletion of Nrf2, demonstrating the Nrf2-dependency of the skewing. Analysis of
      Nrf2-deficient mice revealed that the physiological level of Nrf2 is sufficient
      to contribute to the lineage commitment. This study unequivocally shows that the
      Keap1-Nrf2 system regulates the cell fate determination of HSCs. 

PMID- 24580737
TI  - What is the place of linezolid in the treatment of methicillin-resistant
      Staphylococcus aureus nosocomial pneumonia and complicated skin and soft tissue
      infections in Europe?

PMID- 24580729
TI  - Ontogeny of adrenal-like glucocorticoid synthesis pathway and of 20alpha
      hydroxysteroid dehydrogenase in the mouse lung.
AB  - BACKGROUND: Glucocorticoids exert recognized positive effects on lung
      development. The genes involved in the classical pathway of glucocorticoid
      synthesis normally occurring in adrenals were found to be expressed on gestation
      day (GD) 15.5 in the developing mouse lung. Recently, expression of two of these
      genes was also detected on GD 17.5 suggesting a more complex temporal regulation
      than previously expected. Here, we deepen the knowledge on expression of
      "adrenal" glucocorticoid synthesis genes in the mouse lung during the perinatal
      period and we also study expression of the gene encoding for the steroid
      inactivating enzyme 20alpha-hydroxysteroid dehydrogenase (20alpha-HSD). RESULTS:
      We performed an ontogenic study of P450scc, 3beta-hydroxysteroid
      dehydrogenase/Delta5-Delta4 isomerase 1 (3beta-HSD1), 21-hydroxylase, 11beta
      hydroxylase, 11beta-HSD1, and 11beta-HSD2 expression up to post natal day (PN)
      15. The substrate (progesterone) and the product (deoxycorticosterone) of 21
      hydroxylase are substrates of 20alpha-HSD, thus 20alpha-HSD (Akr1c18) gene
      expression was investigated. In lung samples collected between GD 15.5 and PN 15,
      11beta-hydroxylase was only detected on GD 15.5. In contrast, all the other
      tested genes were expressed throughout the analyzed period with different
      temporal expression patterns. P450scc, 21-hydroxylase, 20alpha-HSD and 11beta
      HSD2 mRNA levels increased after birth with different patterns including an
      increase from PN 3 with a possible sex difference for 21-hydroxylase mRNA. Also,
      the 21-hydroxylase protein was observed by Western blot in perinatal lungs with
      higher levels after birth. CONCLUSION: Progesterone is present at high levels
      during gestation and the product of 21-hydroxylase, deoxycorticosterone, can bind
      the glucocorticoid receptor with an affinity close to that of corticosterone.
      Detection of 21-hydroxylase at the protein level during antenatal lung
      development is the first evidence that the adrenal-like glucocorticoid synthesis
      pathway detected during lung development has the machinery to produce
      glucocorticoids in the fetal lung. Glucocorticoids from lung 21-hydroxylase
      appear to modulate lung ontogenesis through paracrine/intracrine actions.

PMID- 24580733
TI  - Myhre syndrome.
AB  - Myhre syndrome (MS) is a developmental disorder characterized by typical facial
      dysmorphism, thickened skin, joint limitation and muscular pseudohypertrophy.
      Other features include brachydactyly, short stature, intellectual deficiency with
      behavioral problems and deafness. We identified SMAD4 as the gene responsible for
      MS. The identification of SMAD4 mutations in Laryngotracheal stenosis,
      Arthropathy, Prognathism and Short stature (LAPS) cases supports that LAPS and MS
      are a unique entity. The long-term follow up of patients shows that these
      conditions are progressive with life threatening complications. All mutations are
      de novo and changing in the majority of cases Ile500, located in the MH2 domain
      involved in transcriptional activation. We further showed an impairment of the
      transcriptional regulation via TGFbeta target genes in patient fibroblasts.
      Finally, the absence of SMAD4 mutations in three MS cases may support genetic
      heterogeneity. 

PMID- 24580738
TI  - European perspective and update on the management of complicated skin and soft
      tissue infections due to methicillin-resistant Staphylococcus aureus after more
      than 10 years of experience with linezolid.
AB  - Complicated skin and soft tissue infections (cSSTIs) are a diverse group of
      infections, with a range of presentations and microbiological causes.
      Hospitalization is common for patients with a cSSTI, which is treated by drainage
      of the affected area and with antibiotics. Host factors such as co-morbidities,
      and microbial factors, in particular drug resistance, complicate the management
      of these infections. Methicillin-resistant Staphylococcus aureus (MRSA) is an
      important cSSTI pathogen in Europe, and its involvement can be associated with
      poor patient outcomes. European guidelines recommend vancomycin, teicoplanin,
      linezolid, daptomycin, tigecycline or ceftaroline for treatment of MRSA cSSTIs.
      Of primary importance when treating cSSTIs is the agent's clinical efficacy
      against the causative pathogens, as well as its bioavailability in the skin and
      associated structures. Linezolid is well-suited for the treatment of MRSA cSSTIs;
      it achieves high penetration into skin and soft tissues with 100% oral
      bioavailability, and therefore enables an intravenous to oral switch and
      outpatient treatment. When eligible patients are offered oral therapy the
      associated length of hospital stay and overall costs can be reduced. Linezolid
      has demonstrated clinical efficacy and favourable outcomes in patients for the
      treatment of MRSA cSSTIs including the treatment of lower extremity infections.
      Furthermore, efficacy has been documented in key defined populations, such as
      individuals with renal impairment and the obese. The safety profile of linezolid
      is well-documented, making this antibacterial a viable choice for the treatment
      of MRSA cSSTIs. 

PMID- 24580732
TI  - Actor-partner effects associated with experiencing intimate partner violence or
      coercion among male couples enrolled in an HIV prevention trial.
AB  - BACKGROUND: Intimate partner violence (IPV) and coercion have been associated
      with negative health outcomes, including increased HIV risk behaviors, among men
      who have sex with men (MSM). This is the first study to describe the prevalence
      and factors associated with experiencing IPV or coercion among US MSM dyads using
      the actor-partner interdependence model (APIM), an analytic framework to describe
      interdependent outcomes within dyads. METHODS: Among MSM couples enrolled as
      dyads in an HIV prevention randomized controlled trial (RCT), two outcomes are
      examined in this cross-sectional analysis: 1) the actor experiencing physical or
      sexual IPV from the study partner in the past 3-months and 2) the actor feeling
      coerced to participate in the RCT by the study partner. Two multilevel APIM
      logistic regression models evaluated the association between each outcome and
      actor, partner, and dyad-level factors. RESULTS: Of 190 individuals (95 MSM
      couples), 14 reported experiencing physical or sexual IPV from their study
      partner in the past 3 months (7.3%) and 12 reported feeling coerced to
      participate in the RCT by their study partner (6.3%). Results of multivariate
      APIM analyses indicated that reporting experienced IPV was associated (p < 0.1)
      with non-Black/African American actor race, lower actor education, and lower
      partner education. Reporting experienced coercion was associated (p < 0.1) with
      younger actor age and lower partner education. CONCLUSIONS: These findings from
      an HIV prevention RCT for MSM show considerable levels of IPV experienced in the
      past 3-months and coercion to participate in the research study, indicating the
      need for screening tools and support services for these behaviors. The
      identification of factors associated with IPV and coercion demonstrate the
      importance of considering actor and partner effects, as well as dyadic-level
      effects, to improve development of screening tools and support services for these
      outcomes.

PMID- 24580730
TI  - Cathepsin S-mediated autophagic flux in tumor-associated macrophages accelerate
      tumor development by promoting M2 polarization.
AB  - BACKGROUND: Tumor-associated macrophages (TAMs) are the major component of tumor
      infiltrating leukocytes. TAMs are heterogeneous, with distinct phenotypes
      influenced by the microenvironment surrounding tumor tissues, but relatively
      little is known about the key molecular in these cells that contribute to
      malignant phenotypes. Autophagic activity is a critical factor in tumor
      development that contributes to enhancing cellular fitness and survival in the
      hostile tumor microenvironment. However, the molecular basis and relations
      between autophagy and TAMs polarization remain unclear. METHODS: Cathepsin S (Cat
      S) expression was analyzed in human colon carcinoma and normal colon tissues. In
      vivo effects were evaluated using PancO2 subcutaneous tumor model and SL4 hepatic
      metastasis model. Immunofluorescence staining, flow cytometry and real-time PCR
      were done to examine TAMs polarization. Western blotting assay, transmission
      electron microscopy, mCherry-GFP-LC3 transfection and DQ-BSA degradation assays
      were carried out to determine its role in regulating autophagy. RESULTS: In the
      present study, we showed that the enhanced expression of Cat S correlated with
      the severity of histologic grade as well as clinical stage, metastasis, and
      recurrence, which are known indicators of a relatively poor prognosis of human
      colon carcinoma. Cat S knockout led to decreased tumor growth and metastasis.
      Moreover, Cat S knockout inhibited M2 macrophage polarization during tumor
      development. We further demonstrated that Cat S was required for not only
      autophagic flux but also the fusion processes of autophagosomes and lysosomes in
      TAMs. Importantly, we found that Cat S contributed to tumor development by
      regulating the M2 phenotype of TAMs through the activation of autophagy.
      CONCLUSIONS: These results indicated that Cat S-mediated autophagic flux is an
      important mechanism for inducing M2-type polarization of TAMs, which leads to
      tumor development. These data provide strong evidence for a tumor-promoting role
      of autophagy in TAMs and suggest Cat S could be a potential target for cancer
      therapy.

PMID- 24580731
TI  - A common cause of sudden and thunderclap headaches: reversible cerebral
      vasoconstriction syndrome.
AB  - BACKGROUND: Thunderclap headache (TCH) is a sudden headache (SH) with accepted
      criteria of severe intensity and onset to peak within one minute. It is a well
      known presentation for subarachnoid hemorrhage (SAH) but most patients with TCH
      or SH run a benign course without identifiable causes. Reversible cerebral
      vasoconstriction syndrome (RCVS), a recently recognized syndrome characterized by
      recurrent TCH attacks, has been proposed to account for most of these patients.
      METHODS: We recruited consecutive patients presenting with SH at our headache
      clinic. Computed tomography and/or magnetic resonance imaging with angiography
      were performed to exclude structural causes and to identify vasoconstriction.
      Catheter angiography and lumbar puncture were performed with patients consent.
      Reversibility of vasoconstriction was confirmed by follow-up study. RESULTS: From
      July 2010 to June 2013, 31 patients with SH were recruited. Twenty-four (72.7%)
      of these SH patients exhibited headache fulfilling the TCH criteria. The
      diagnosis of RCVS was confirmed in 14 (45.2%) of patients with SH and 11 (45.8%)
      of patients with TCH. Other diagnoses were as follows: primary headaches (SH:
      41.9%, TCH: 45.8%) and other secondary causes (SH: 12.9%, TCH: 8.3%). Compared
      with non-RCVS patients, patients with RCVS were older (50.8 +/- 9.3 years vs.
      40.8 +/- 10.0 years, P = 0.006) and less likely to experience short headache
      duration of < 1 hour (23.1% vs. 78.6%, P = 0.007). Patients with RCVS were more
      likely to cite bathing (42.9% vs. 0%, P = 0.004) and less likely to cite exertion
      (0% vs. 29.4%, P = 0.048) as headache triggers. CONCLUSIONS: Reversible cerebral
      vasoconstriction syndrome is a common cause of SH and TCH. Considering the
      potential mortality and morbidity of RCVS, systemic examination of cerebral
      vessels should be performed in these patients.

PMID- 24580740
TI  - The use of keratin-based wound products on refractory wounds.
AB  - Keratin proteins have been shown to play a key role in wound healing. Controlled
      keratin gene (KRT) expression promotes cell growth, migration and
      differentiation, and as an example of the importance of keratin proteins, absence
      of KRT17 has been shown to delay wound closure. In addition, downregulation of
      KRT6 and KRT16 in non-healing chronic venous ulcers suggests that deregulation of
      keratin expression contributes to non-healing phenotype. A sample of 45 chronic
      wounds of mixed aetiologies presenting in 31 patients were treated with keratin
      based novel topical wound healing products. Thirty-seven wounds or 82% of wounds
      were either healed or reduced in size of >50% during treatment, with 29 (64%)
      healing completely and an additional 8 wounds experiencing 50% wound size
      reduction or greater. Of the wounds that responded, 15 required antimicrobial
      treatment during their course of treatment, suggesting that keratin dressing
      treatment should be interrupted briefly and then restarted when wound infection
      occur. 

PMID- 24580741
TI  - Probabilistic approaches to alignment with tandem repeats.
AB  - BACKGROUND: Short tandem repeats are ubiquitous in genomic sequences and due to
      their complex evolutionary history pose a challenge for sequence alignment tools.
      RESULTS: To better account for the presence of tandem repeats in pairwise
      sequence alignments, we propose a simple tractable pair hidden Markov model that
      explicitly models their presence. Using the framework of gain functions, we
      design several optimization criteria for decoding this model and describe
      resulting decoding algorithms, ranging from the traditional Viterbi and posterior
      decoding to block-based decoding algorithms tailored to our model. We compare the
      accuracy of individual decoding algorithms on simulated and real data and find
      that our approach is superior to the classical three-state pair HMM. CONCLUSIONS:
      Our study illustrates versatility of pair hidden Markov models coupled with
      appropriate decoding criteria as a modeling tool for capturing complex sequence
      features.

PMID- 24580739
TI  - European perspective and update on the management of nosocomial pneumonia due to
      methicillin-resistant Staphylococcus aureus after more than 10 years of
      experience with linezolid.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) is an important cause of
      antimicrobial-resistant hospital-acquired infections worldwide and remains a
      public health priority in Europe. Nosocomial pneumonia (NP) involving MRSA often
      affects patients in intensive care units with substantial morbidity, mortality
      and associated costs. A guideline-based approach to empirical treatment with an
      antibacterial agent active against MRSA can improve the outcome of patients with
      MRSA NP, including those with ventilator-associated pneumonia. New methods may
      allow more rapid or sensitive diagnosis of NP or microbiological confirmation in
      patients with MRSA NP, allowing early de-escalation of treatment once the
      pathogen is known. In Europe, available antibacterial agents for the treatment of
      MRSA NP include the glycopeptides (vancomycin and teicoplanin) and linezolid
      (available as an intravenous or oral treatment). Vancomycin has remained a
      standard of care in many European hospitals; however, there is evidence that it
      may be a suboptimal therapeutic option in critically ill patients with NP because
      of concerns about its limited intrapulmonary penetration, increased
      nephrotoxicity with higher doses, as well as the emergence of resistant strains
      that may result in increased clinical failure. Linezolid has demonstrated high
      penetration into the epithelial lining fluid of patients with ventilator
      associated pneumonia and shown statistically superior clinical efficacy versus
      vancomycin in the treatment of MRSA NP in a phase IV, randomized, controlled
      study. This review focuses on the disease burden and clinical management of MRSA
      NP, and the use of linezolid after more than 10 years of clinical experience.

PMID- 24580734
TI  - microRNA156-targeted SPL/SBP box transcription factors regulate tomato ovary and
      fruit development.
AB  - Fruit ripening in tomato (Solanum lycopersicum L.) is well understood at the
      molecular level. However, information regarding genetic pathways associated with
      tomato ovary and early fruit development is still lacking. Here, we investigate
      the possible role(s) of the microRNA156/SQUAMOSA promoter-binding protein-like
      (SPL or SBP box) module (miR156 node) in tomato ovary development. miR156
      targeted S. lycopersicum SBP genes were dynamically expressed in developing
      flowers and ovaries, and miR156 was mainly expressed in meristematic tissues of
      the ovary, including placenta and ovules. Transgenic tomato cv. Micro-Tom plants
      over-expressing the AtMIR156b precursor exhibited abnormal flower and fruit
      morphology, with fruits characterized by growth of extra carpels and ectopic
      structures. Scanning electron microscopy and histological analyses showed the
      presence of meristem-like structures inside the ovaries, which are probably
      responsible for the ectopic organs. Interestingly, expression of genes associated
      with meristem maintenance and formation of new organs, such as LeT6/TKN2 (a KNOX
      like class I gene) and GOBLET (a NAM/CUC-like gene), was induced in developing
      ovaries of transgenic plants as well as in the ovaries of the natural mutant
      Mouse ear (Me), which also displays fruits with extra carpels. Conversely,
      expression of the MADS box genes MACROCALYX (MC) and FUL1/TDR4, and the LEAFY
      ortholog FALSIFLORA, was repressed in the developing ovaries of miR156 over
      expressors, suggesting similarities with Arabidopsis at this point of the
      miR156/SPL pathway but with distinct functional consequences in reproductive
      development. Altogether, these observations suggest that the miR156 node is
      involved in maintenance of the meristematic state of ovary tissues, thereby
      controlling initial steps of fleshy fruit development and determinacy. 

PMID- 24580742
TI  - Patients who present late to HIV care and associated risk factors in Nigeria.
AB  - OBJECTIVES: Our objectives were to assess trends in late presentation and
      advanced HIV disease (AHD) and determine associated risk factors. METHODS: We
      conducted a retrospective cohort analysis of patients who had received care and
      treatment at the AIDS Prevention Initiative Nigeria Plus (APIN)/Harvard School of
      Public Health-President's Emergency Plan for AIDS Relief (PEPFAR) programme at
      the Jos University Teaching Hospital, Jos, Nigeria from 2005 to 2010. We used the
      European Consensus Definition to assess trends in late presentation (CD4 count <
      350 cells/MUL or AIDS-defining illness) and AHD (CD4 count < 200 cells/MUL or
      AIDS-defining illness) and evaluated associated risk factors using logistic
      regression methods. RESULTS: Among 14,487 eligible patients, 12,401 (85.6%) were
      late presenters and 9127 (63.0%) presented with AHD. Late presentation decreased
      from 88.9% in 2005 to 80.1% in 2010 (P < 0.001). Similarly, AHD decreased from
      67.8% in 2005 to 53.6% in 2010 (P < 0.001). In logistic regression models
      adjusting for sociodemographic and biological variables, male sex [adjusted odds
      ratio (aOR) = 1.80; 95% confidence interval (CI) 1.60-2.04], older age (aOR =
      1.37; 95% CI 1.22-1.54), civil service employment (aOR = 1.48; 95% CI 1.00-2.21),
      referral from out-patient (aOR = 2.18; 95% CI 1.53-3.08) and in-patient (aOR =
      1.55; 95% CI 1.11-2.17) services, and hepatitis B virus (aOR = 1.43; 95% CI 1.26
      1.63) and hepatitis C virus (aOR = 1.18; 95% CI 1.02-1.37) coinfections were
      associated with late presentation. Predictors of AHD were male sex (aOR = 1.67;
      95% CI 1.54-1.82), older age (aOR = 1.26; 95% CI 1.16-1.36), unemployment (aOR =
      1.34; 95% CI 1.00-1.79), referral from out-patient (aOR = 2.40; 95% CI 1.84-3.14)
      and in-patient (aOR = 1.97; 95% CI 1.51-2.57) services and hepatitis B virus
      coinfection (aOR = 1.30; 95% CI 1.19-1.42). CONCLUSIONS: Efforts to reduce the
      proportion of patients who first seek care at late stages of disease are needed.
      The identified risk factors should be utilized in formulating targeted public
      health interventions to improve early diagnosis and presentation for HIV care.

PMID- 24580743
TI  - The potential dual effects of sevoflurane on AKT/GSK3beta signaling pathway.
AB  - BACKGROUND: Anesthesia with multiple exposures of commonly used inhalation
      anesthetic sevoflurane induces neuroinflammation and cognitive impairment in
      young mice, but anesthesia with a single exposure to sevoflurane does not.
      AKT/glycogen synthase kinase 3beta (GSK3beta) signaling pathway is involved in
      neurotoxicity and neurobehavioral deficits. However, whether sevoflurane can
      induce a dual effect (increase versus decrease) on the activation of AKT/GSK3beta
      signaling pathway remains to be determined. We therefore set out to assess the
      effects of sevoflurane on AKT/GSK3beta signaling pathway in vivo and in vitro.
      METHODS: Six day-old wild-type mice were exposed to 3% sevoflurane two hours
      daily for one or three days. In the in vitro studies, H4 human neuroglioma cells
      were treated with 4% sevoflurane for two or six hours. We then determined the
      effects of different sevoflurane treatments on the levels of phosphorylated (P)
      GSK3beta(ser9) and P-AKT(ser473) by using Western blot analysis. RESULTS: Here we
      show that anesthesia with 3% sevoflurane two hours daily for one day increased
      the levels of P-GSK3beta(ser9) and P-AKT(ser473), but the anesthesia with 3%
      sevoflurane daily for three days decreased them in the mice. The treatment with
      4% sevoflurane for two hours increased, but the treatment with 4% sevoflurane for
      six hours decreased, the levels of P-GSK3beta(ser9) and P-AKT(ser473) in the H4
      human neuroglioma cells. CONCLUSIONS: Anesthetic sevoflurane might induce a dual
      effect (increase versus decrease) on the activation of the AKT/GSK3beta signaling
      pathway. These studies have established a system to perform further studies to
      determine the effects of sevoflurane on brain function.

PMID- 24580744
TI  - Use of prehospital ultrasound in North America: a survey of emergency medical
      services medical directors.
AB  - BACKGROUND: Advances in ultrasound imaging technology have made it more
      accessible to prehospital providers. Little is known about how ultrasound is
      being used in the prehospital environment and we suspect that it is not widely
      used in North America at this time. We believe that EMS system characteristics
      such as provider training, system size, population served, and type of transport
      will be associated with use or non-use of ultrasound. Our study objective was to
      describe the current use of prehospital ultrasound in North America. METHODS:
      This study was a cross-sectional survey distributed to EMS directors on the
      National Association of EMS Physicians (NAEMSP) mailing list. Respondents had the
      option to complete a paper or electronic survey. RESULTS: Of the 755 deliverable
      surveys we received 255 responses from across Canada and the United states for an
      overall response rate of 30%. Of respondents, 4.1% of EMS systems (95% CI 1.9,
      6.3) reported currently using ultrasound and an additional 21.7% (95% CI 17,
      26.4) are considering implementing ultrasound. EMS services using ultrasound have
      a higher proportion of physicians (p < 0.001) as their highest trained
      prehospital providers when compared to the survey group as a whole. The most
      commonly cited current and projected applications are Focused Abdominal
      Sonography for Trauma (FAST) and assessment of pulseless electrical activity
      (PEA) arrest. The cost of equipment and training are the most significant
      barriers to implementation of ultrasound. Most medical directors want evidence
      that prehospital ultrasound improves patient outcomes prior to implementation.
      CONCLUSIONS: Prehospital ultrasound is infrequently used in North America and
      there are a number of barriers to its implementation, including costs of
      equipment and training and limited evidence demonstrating improved outcomes. A
      research agenda for prehospital ultrasound should focus on patient-important
      outcomes such as morbidity and mortality. Two commonly used indications that
      could be a focus of standardized training programs are the FAST exam, and
      assessment of PEA arrest.

PMID- 24580745
TI  - Practice patterns and preferences of obstetricians and gynecologists regarding
      thromboprophylaxis at the time of Cesarean section.
AB  - OBJECTIVE: Our survey aimed to identify knowledge and application of guidelines
      in the United States by assessing practicing obstetricians and gynecologists
      (OBGYN) use of thromboprophylaxis, preferred methods and whether their type of
      practice influenced their choices. STUDY DESIGN: A cross-sectional survey of
      fellows of the American College of Obstetricians and Gynecologists (ACOG) was
      performed. A 21-item paper and electronic questionnaire was sent to each
      participant. A total of three mailings were carried out. RESULTS: In total, 400
      OBGYN were invited to participate. Questionnaires were returned by 209 (52.3%),
      157 (75.1%) of whom provided prenatal care within the last year. All respondents
      used at least one method of thromboprophylaxis routinely. About 92.4% used
      pneumatic compression devices. An equal proportion used unfractionated heparin
      and low molecular weight heparin routinely (17.8%). About 19.1% routinely used
      combination prophylaxis. In total, 77.1% (n = 121) used the ACOG guidelines.
      Local hospital guidelines were referenced by 38.2% (n = 60). Other guidelines
      referenced were the ACCP guideline (n = 34, 21.7%) and several international
      guidelines (n = 5, 3.3%). CONCLUSION: Awareness of the risk of thromboembolism
      around delivery by cesarean section is high among OBGYN practitioners. Broadening
      guidelines to encompass all deliveries, not only cesareans, with a focus on
      identifying the patient at risk, would likely be successful.

PMID- 24580747
TI  - Validation of a food frequency questionnaire to assess food group intake by
      pregnant women.
AB  - BACKGROUND: Previous studies conducted among pregnant women to test the accuracy
      of food frequency questionnaires (FFQ) for estimating food group intake were
      restricted to one specific trimester of pregnancy. The present study aimed to
      validate a FFQ for assessing the intake of food groups throughout pregnancy.
      METHODS: In total, 75 adult pregnant Brazilian women were evaluated. Dietary
      intake was assessed by the FFQ (completed at the third trimester of pregnancy)
      and by three 24-h dietary recalls; one in each trimester of pregnancy. RESULTS:
      The food items were classified into 20 groups. Adequate deatenuatted Pearson
      correlation coefficients (>0.4) were observed for the intake of bread/cake,
      butter/margarine; milk/dairy products; soft drinks/artificial juices; coffee/tea;
      and pastries/sandwiches. The FFQ served poorly for estimating fruit and vegetable
      intake. A high percentage (>70%) of women were classified into the same or
      adjacent quartiles for estimates of cookies/crackers, butter/margarine,
      milk/dairy products, fruit juices, soft drinks/artificial juices, coffee/tea,
      roots, rice, beans, meat/chicken/sausages, fried foods, fish, eggs,
      sweets/sugars, and pastries/sandwiches. Nevertheless, the agreement of joint
      classification between the dietary methods was mostly into adjacent quartiles,
      rather than in the same quartile, and low values of kappa were found.
      CONCLUSIONS: The data reported in the present study suggest that the FFQ might
      not be an appropriate dietary method for evaluating food group intake throughout
      pregnancy. The joint classification between methods by categories of intake of
      food groups was mostly into adjacent quartiles, which could lead to attenuated
      associations when investigating diet-disease relationships during pregnancy.

PMID- 24580748
TI  - Tea polyphenols alleviate high fat and high glucose-induced endothelial
      hyperpermeability by attenuating ROS production via NADPH oxidase pathway.
AB  - BACKGROUND: Hyperglycemia-induced endothelial hyperpermeability is crucial to
      cardiovascular disorders and macro-vascular complications in diabetes mellitus.
      The objective of this study is to investigate the effects of green tea
      polyphenols (GTPs) on endothelial hyperpermeability and the role of nicotinamide
      adenine dinucleotide phosphate (NADPH) pathway. METHODS: Male Wistar rats fed on
      a high fat diet (HF) were treated with GTPs (0, 0.8, 1.6, 3.2 g/L in drinking
      water) for 26 weeks. Bovine aortic endothelial cells (BAECs) were treated with
      high glucose (HG, 33 mmol/L) and GTPs (0.0, 0.4, or 4 MUg/mL) for 24 hours in
      vitro. The endothelial permeabilities in rat aorta and monolayer BAECs were
      measured by Evans blue injection method and efflux of fluorescein isothiocyanate
      (FITC)-dextran, respectively. The reactive oxygen species (ROS) levels in rat
      aorta and monolayer BAECs were measured by dihydroethidium (DHE) and 2', 7'
      dichloro-fluorescein diacetate (DCFH-DA) fluorescent probe, respectively. Protein
      levels of NADPH oxidase subunits were determined by Western-blot. RESULTS: HF
      diet-fed increased the endothelial permeability and ROS levels in rat aorta while
      HG treatments increased the endothelial permeability and ROS levels in cultured
      BAECs. Co-treatment with GTPs alleviated those changes both in vivo and in vitro.
      In in vitro studies, GTPs treatments protected against the HG-induced over
      expressions of p22phox and p67phox. Diphenylene iodonium chloride (DPI), an
      inhibitor of NADPH oxidase, alleviated the hyperpermeability induced by HG.
      CONCLUSIONS: GTPs could alleviate endothelial hyperpermeabilities in HF diet-fed
      rat aorta and in HG treated BAECs. The decrease of ROS production resulting from
      down-regulation of NADPH oxidase contributed to the alleviation of endothelial
      hyperpermeability.

PMID- 24580749
TI  - Baseline elevated Lp-PLA2 is associated with increased risk for re-stenosis after
      stent placement.
AB  - BACKGROUND: Lipoprotein associated phospholipase A2 (Lp-PLA2) is a novel
      biomarker for cardiovascular risk prediction. Whether increased Lp-PLA2 level is
      associated with re-stenosis after stent-placement is unclear. METHODS: Totally
      326 participants eligible for stent-placement were enrolled and divided into two
      groups according to baseline Lp-PLA2 levels (named normal and elevated groups).
      Baseline characteristics and clinical outcomes were compared between normal and
      elevated groups. The relationships between Lp-PLA2 and other risk factors with re
      stenosis were evaluated. RESULTS: Only the between-group difference of Lp-PLA2
      was significant (123.2 +/- 33.6 ng/mL vs 336.8 +/- 85.4 ng/mL, P < 0.001) while
      other demographic and clinical characteristics between these two groups were
      comparable. Approximately 55.1% and 58.5% of participants in normal and elevated
      groups presented with acute coronary syndrome, and the percentage of tri-vessels
      stenoses was significantly higher in elevated group (40.8% vs 32.1%, P = 0.016).
      Nearly 96.0% and 94.0% of participants in normal and elevated Lp-PLA2 groups were
      placed with drug-eluting stents, and the others were with bare-metal stents.
      After 1 year's follow-up, the incidence of clinical end-points was comparable
      (13.3% vs 15.4%, P = 0.172). Nevertheless, the incidence of re-stenosis was
      marginally higher in elevated Lp-PLA2 group (8.5% versus 4.6%, P = 0.047). With
      multivariate analysis, after adjustment for other risk factors, Lp-PLA2 remained
      an independent predictor for re-stenosis with a hazard ratio of 1.140. No
      synergistic effect between Lp-PLA2 and other risk factors for re-stenosis was
      found. CONCLUSION: Increased Lp-PLA2 level is associated with an increased risk
      of re-stenosis. Lp-PLA2 assessment may be useful in predicting subjects who are
      at increased risk for re-stenosis.

PMID- 24580750
TI  - Evaluating the effectiveness of a training program that builds teachers'
      capability to identify and appropriately refer middle and high school students
      with mental health problems in Brazil: an exploratory study.
AB  - BACKGROUND: In Brazil, like many countries, there has been a failure to identify
      mental health problems (MHP) in young people and refer them to appropriate care
      and support. The school environment provides an ideal setting to do this.
      Therefore, effective programs need to be developed to train teachers to identify
      and appropriately refer children with possible MHP. We aimed to evaluate
      teachers' ability to identify and appropriately refer students with possible MHP,
      and the effectiveness of a psychoeducational strategy to build teachers'
      capability in this area. METHODS: To meet the first objective, we conducted a
      case-control study using a student sample. To meet the second, we employed
      longitudinal design with repeated measures before and after introducing the
      psychoeducational strategy using a teacher sample. In the case control study, the
      Youth Self-Report was used to investigate internalizing and externalizing
      problems. Before training, teachers selected 26 students who they thought were
      likely to have MHP. Twenty-six non-selected students acted as controls and were
      matched by gender, age and grade. The underlying principle was that if teachers
      could identify abnormal behaviors among their actual students, those with some
      MHP would likely be among the case group and those without among the control
      group. In the longitudinal study, 32 teachers were asked to evaluate six
      vignettes that highlighted behaviors indicating a high risk for psychosis,
      depression, conduct disorder, hyperactivity, mania, and normal adolescent
      behavior. We calculated the rates of correct answers for identifying the
      existence of some MHP and the need for referral before and after training;
      teachers were not asked to identify the individual conditions. RESULTS: Teachers
      were already able to identify the most symptomatic students, who had both
      internalizing and externalizing problems, as possibly having MHP, but teachers
      had difficulty in identifying students with internalizing problems alone. At
      least 50.0% of teachers learned to identify hypothetical cases as problematic and
      to make the appropriate referral, and 60.0% of teachers who before training could
      not identify normal adolescence learned to do so. CONCLUSIONS: The strategy was
      partially effective but could be improved mainly by extending its duration, and
      including discussion of actual cases.

PMID- 24580751
TI  - Tips and tricks of inflatable penile prosthesis reservoir placement: a case
      presentation and discussion.
AB  - INTRODUCTION: There have been many advances in the inflatable penile prosthesis
      (IPP) since the 1970s. While these devices were initially fraught with mechanical
      malfunction, the most recent models prove to be much more reliable. Although
      reservoir complications are not common, when they do occur, it typically involves
      damage to the surrounding tissues. The ability to recognize and treat these
      complications is paramount for any surgeon that routinely places IPPs. AIM: The
      aim of this article was to present a unique reservoir-related complication as
      well as perform a literature review of reservoir-related complications and
      techniques for reservoir placement, and provide a summary of dimensions and
      technical aspects of commonly used reservoirs. METHODS: We reviewed a unique
      reservoir-related complication that presented to our institution with urinary
      retention and constipation. We also reviewed reservoir-related complications
      since 1984, reviewed the most recent surgical techniques involved in reservoir
      placement, and summarized the dimensions and technical characteristics of both
      the American Medical System and Coloplast reservoirs. MAIN OUTCOME MEASURE: A
      reservoir-related complication that resulted in urinary retention and
      constipation is the main outcome measure. RESULTS: Although uncommon, reservoir
      complications do occur. The most common case report complication in the published
      literature is bladder erosion followed by external iliac compression, ileal
      conduit erosion, and small bowel obstruction. The case that presented at our
      institution was the result of a reservoir that was improperly placed in the
      perineum, causing urinary retention and constipation due to the compression of
      the bulbar urethra and rectum. CONCLUSIONS: In this era, mechanical failures of
      IPP reservoirs are rare as most complications occur due to damage of the
      surrounding tissues. Prevention, diagnosis, and treatment of these complications
      are important for any surgeon that implants IPPs.

PMID- 24580752
TI  - Effect of Poloxamer 407 as a carrier vehicle on rotator cuff healing in a rat
      model.
AB  - BACKGROUND: In vivo studies showing the effects of biologic healing-promoting
      factors on tendon-to-bone healing after rotator cuff repair have focused only on
      biologic healing-promoting factors and have not taken into consideration the
      effect of the carrier vehicle. Moreover, most studies have evaluated the healing
      process using different carrier vehicles, each of which may have specific effects
      on tendon healing. This may explain the large variability seen in outcomes in
      research studies. In this study, we investigated the effects of Poloxamer 407 as
      a carrier vehicle on rotator cuff healing at the repair site and compared it with
      those of a collagen sponge, which is a commonly used carrier vehicle. METHODS:
      Fifty-seven adult male Sprague-Dawley rats underwent detachment and immediate
      repair of the bilateral supraspinatus tendons. Rats were randomly assigned to
      three groups: repair only, repair with collagen sponge, and repair with Poloxamer
      407. The repairs were evaluated at 1, 2, 4, and 8 weeks after surgery with
      histological analysis and biomechanical testing. RESULTS: At 4 weeks, more
      cellular organization, a greater number of collagen fibers, and increased
      maturity of collagen fibers were observed in the repair with Poloxamer 407 group
      than in the other groups. The repair with collagen sponge group had delayed
      development and collagen fiber maturation. Significant differences in the
      biomechanical properties were found between groups at 4 weeks. Stiffness in the
      case of the repair with Poloxamer 407 group was significantly higher than that in
      the repair with collagen sponge group. The modulus was significantly lower in the
      repair with collagen sponge group than in the repair only group. However, the use
      of Poloxamer 407 versus the collagen sponge did not significantly affect the
      biomechanical properties of the repaired tendons at 8 weeks. CONCLUSIONS: Carrier
      vehicles may have differing effects at the early stages of rotator cuff healing.
      The use of Poloxamer 407 as a carrier vehicle may be useful for promoting the
      early stages of healing and for maintaining the initial biomechanical properties
      of the repaired rotator cuff tendon.

PMID- 24580754
TI  - Multi-disciplinary research across the patient journey.

PMID- 24580753
TI  - Inferring gene function from evolutionary change in signatures of translation
      efficiency.
AB  - BACKGROUND: The genetic code is redundant, meaning that most amino acids can be
      encoded by more than one codon. Highly expressed genes tend to use optimal codons
      to increase the accuracy and speed of translation. Thus, codon usage biases
      provide a signature of the relative expression levels of genes, which can,
      uniquely, be quantified across the domains of life. RESULTS: Here we describe a
      general statistical framework to exploit this phenomenon and to systematically
      associate genes with environments and phenotypic traits through changes in codon
      adaptation. By inferring evolutionary signatures of translation efficiency in 911
      bacterial and archaeal genomes while controlling for confounding effects of
      phylogeny and inter-correlated phenotypes, we linked 187 gene families to 24
      diverse phenotypic traits. A series of experiments in Escherichia coli revealed
      that 13 of 15, 19 of 23, and 3 of 6 gene families with changes in codon
      adaptation in aerotolerant, thermophilic, or halophilic microbes. Respectively,
      confer specific resistance to, respectively, hydrogen peroxide, heat, and high
      salinity. Further, we demonstrate experimentally that changes in codon optimality
      alone are sufficient to enhance stress resistance. Finally, we present evidence
      that multiple genes with altered codon optimality in aerobes confer oxidative
      stress resistance by controlling the levels of iron and NAD(P)H. CONCLUSIONS:
      Taken together, these results provide experimental evidence for a widespread
      connection between changes in translation efficiency and phenotypic adaptation.
      As the number of sequenced genomes increases, this novel genomic context method
      for linking genes to phenotypes based on sequence alone will become increasingly
      useful.

PMID- 24580755
TI  - CDSbank: taxonomy-aware extraction, selection, renaming and formatting of protein
      coding DNA or amino acid sequences.
AB  - BACKGROUND: Protein-coding DNA sequences and their corresponding amino acid
      sequences are routinely used to study relationships between sequence, structure,
      function, and evolution. The rapidly growing size of sequence databases increases
      the power of such comparative analyses but it makes it more challenging to
      prepare high quality sequence data sets with control over redundancy, quality,
      completeness, formatting, and labeling. Software tools for some individual steps
      in this process exist but manual intervention remains a common and time consuming
      necessity. DESCRIPTION: CDSbank is a database that stores both the protein-coding
      DNA sequence (CDS) and amino acid sequence for each protein annotated in Genbank.
      CDSbank also stores Genbank feature annotation, a flag to indicate incomplete 5'
      and 3' ends, full taxonomic data, and a heuristic to rank the scientific interest
      of each species. This rich information allows fully automated data set
      preparation with a level of sophistication that aims to meet or exceed manual
      processing. Defaults ensure ease of use for typical scenarios while allowing
      great flexibility when needed. Access is via a free web server at
      http://hazeslab.med.ualberta.ca/CDSbank/. CONCLUSIONS: CDSbank presents a user
      friendly web server to download, filter, format, and name large sequence data
      sets. Common usage scenarios can be accessed via pre-programmed default choices,
      while optional sections give full control over the processing pipeline.
      Particular strengths are: extract protein-coding DNA sequences just as easily as
      amino acid sequences, full access to taxonomy for labeling and filtering,
      awareness of incomplete sequences, and the ability to take one protein sequence
      and extract all synonymous CDS or identical protein sequences in other species.
      Finally, CDSbank can also create labeled property files to, for instance,
      annotate or re-label phylogenetic trees.

PMID- 24580756
TI  - Fermented soshiho-tang with Lactobacillus plantarum enhances the
      antiproliferative activity in vascular smooth muscle cell.
AB  - BACKGROUND: Soshiho-tang (SST) is a traditional medicine widely used for the
      treatment of chronic hepatitis. SST has been shown to confer a variety of
      pharmacological activities, including prevention of hepatotoxicity, promotion of
      liver regeneration, and modulation of liver fibrosis. In this study, we
      investigated the antiproliferative activity of native and fermented (FSST)
      formulations of SST in vascular smooth muscle cells (VSMCs) and examined the
      potential underlying mechanisms driving these effects. METHODS: SST, along with
      preparations fermented with Lactobacillus plantarum KFRI-144 (S-A144), L.
      amylophilus KFRI-161 (S-A161) and L. bulgaricus KFRI-344 (S-A344), were
      investigated to determine their effects on the proliferation and viability of
      VSMCs, along with the signalling pathways underlying these effects. RESULTS: S
      A144 exhibited a strong, dose-dependent inhibition of VSMC proliferation relative
      to untreated controls, but the others did not affect. In addition, S-A144
      significantly decreased the phosphorylation of Akt and PLCgamma1 in a dose
      dependent manner and induced cell cycle arrest at the G0/G1 phase characterised
      by decreased expression of CDKs, cyclins and PCNA. CONCLUSIONS: The findings
      suggest that S-A144 exhibit enhanced inhibition of PDGF-BB-induced VSMC
      proliferation comparison to S-AOR through the suppression of cell cycle
      progression and expression of cell cycle-related proteins, along with the
      downregulation of Akt phosphorylation.

PMID- 24580757
TI  - European mitochondrial haplogroups are not associated with hepatitis C virus
      (HCV) treatment response in HIV/HCV-coinfected patients.
AB  - OBJECTIVES: Mitochondria are multifunctional organelles with a key role in the
      innate immune response against viral infections. Mitochondrial DNA (mtDNA)
      haplogroups have been related to AIDS progression and CD4 T-cell recovery in HIV
      infected patients, and to a delay in the development of liver fibrosis in
      HIV/hepatitis C virus (HCV)-coinfected patients. We performed a study to
      investigate whether mtDNA haplogroups may be associated with HCV treatment
      response in HIV/HCV-coinfected patients on pegylated interferon (pegIFN) plus
      ribavirin (RBV). METHODS: We performed a retrospective study in 304 patients who
      completed a course of HCV therapy. mtDNA polymorphisms were genotyped using
      Sequenom's MassARRAY platform. The interleukin-28B (IL-28B) polymorphism
      (rs12980275) was genotyped using the GoldenGate(r) assay. Sustained virological
      response (SVR) was defined as an undetectable HCV viral load at week 24 after the
      end of treatment. The statistical analysis was carried out using on-treatment
      data. RESULTS: The SVR rates were 52.6% (160 of 304) for all patients, and 37.8%
      (46 of 201) for patients with HCV genotype 1 or 4 vs. 81.4% (83 of 102) for
      patients with HCV genotype 2 or 3 (P < 0.001). No significant associations were
      found between mtDNA haplogroup and SVR when all patients were included in the
      analysis and when patients were stratified by HCV genotype (i.e. those with
      genotypes 1/4 and 2/3 analysed separately) or IL-28B rs12980275 genotype.
      CONCLUSIONS: European mtDNA haplogroups were not related to HCV treatment
      response in HIV/HCV-coinfected patients on pegIFN-alpha/RBV therapy.

PMID- 24580760
TI  - Cardiovascular surgery and nephrology.

PMID- 24580759
TI  - Severe obesity in children: prevalence, persistence and relation to hypertension.
AB  - BACKGROUND: Newer approaches for classifying gradations of pediatric obesity by
      level of body mass index (BMI) percentage above the 95th percentile have recently
      been recommended in the management and tracking of obese children. Examining the
      prevalence and persistence of severe obesity using such methods along with the
      associations with other cardiovascular risk factors such as hypertension is
      important for characterizing the clinical significance of severe obesity
      classification methods. METHODS: This retrospective study was conducted in an
      integrated healthcare delivery system to characterize obesity and obesity
      severity in children and adolescents by level of body mass index (BMI) percentage
      above the 95th BMI percentile, to examine tracking of obesity status over 2-3
      years, and to examine associations with blood pressure. Moderate obesity was
      defined by BMI 100-119% of the 95th percentile and severe obesity by BMI >=120% *
      95th percentile. Hypertension was defined by 3 consecutive blood pressures >=95th
      percentile (for age, sex and height) on separate days and was examined in
      association with obesity severity. RESULTS: Among 117,618 children aged 6-17
      years with measured blood pressure and BMI at a well-child visit during 2007
      2010, the prevalence of obesity was 17.9% overall and was highest among Hispanics
      (28.9%) and blacks (20.5%) for boys, and blacks (23.3%) and Hispanics (21.5%) for
      girls. Severe obesity prevalence was 5.6% overall and was highest in 12-17 year
      old Hispanic boys (10.6%) and black girls (9.5%). Subsequent BMI obtained 2-3
      years later also demonstrated strong tracking of severe obesity. Stratification
      of BMI by percentage above the 95th BMI percentile was associated with a graded
      increase in the risk of hypertension, with severe obesity contributing to a 2.7
      fold greater odds of hypertension compared to moderate obesity. CONCLUSION:
      Severe obesity was found in 5.6% of this community-based pediatric population,
      varied by gender and race/ethnicity (highest among Hispanics and blacks) and
      showed strong evidence for persistence over several years. Increasing gradation
      of obesity was associated with higher risk for hypertension, with a nearly three
      fold increased risk when comparing severe to moderate obesity, underscoring the
      heightened health risk associated with severe obesity in children and
      adolescents.

PMID- 24580758
TI  - Agreement between self-reported and general practitioner-reported chronic
      conditions among multimorbid patients in primary care - results of the MultiCare
      Cohort Study.
AB  - BACKGROUND: Multimorbidity is a common phenomenon in primary care. Until now, no
      clinical guidelines for multimorbidity exist. For the development of these
      guidelines, it is necessary to know whether or not patients are aware of their
      diseases and to what extent they agree with their doctor. The objectives of this
      paper are to analyze the agreement of self-reported and general practitioner
      reported chronic conditions among multimorbid patients in primary care, and to
      discover which patient characteristics are associated with positive agreement.
      METHODS: The MultiCare Cohort Study is a multicenter, prospective, observational
      cohort study of 3,189 multimorbid patients, ages 65 to 85. Data was collected in
      personal interviews with patients and GPs. The prevalence proportions for 32
      diagnosis groups, kappa coefficients and proportions of specific agreement were
      calculated in order to examine the agreement of patient self-reported and general
      practitioner-reported chronic conditions. Logistic regression models were
      calculated to analyze which patient characteristics can be associated with
      positive agreement. RESULTS: We identified four chronic conditions with good
      agreement (e.g. diabetes mellitus kappa = 0.80;PA = 0,87), seven with moderate
      agreement (e.g. cerebral ischemia/chronic stroke kappa = 0.55;PA = 0.60),
      seventeen with fair agreement (e.g. cardiac insufficiency kappa = 0.24;PA = 0.36)
      and four with poor agreement (e.g. gynecological problems kappa = 0.05;PA =
      0.10).Factors associated with positive agreement concerning different chronic
      diseases were sex, age, education, income, disease count, depression, EQ VAS
      score and nursing care dependency. For example: Women had higher odds ratios for
      positive agreement with their GP regarding osteoporosis (OR = 7.16). The odds
      ratios for positive agreement increase with increasing multimorbidity in almost
      all of the observed chronic conditions (OR = 1.22-2.41). CONCLUSIONS: For
      multimorbidity research, the knowledge of diseases with high disagreement levels
      between the patients' perceived illnesses and their physicians' reports is
      important. The analysis shows that different patient characteristics have an
      impact on the agreement. Findings from this study should be included in the
      development of clinical guidelines for multimorbidity aiming to optimize health
      care. Further research is needed to identify more reasons for disagreement and
      their consequences in health care. TRIAL REGISTRATION: ISRCTN89818205.

PMID- 24580761
TI  - Update and outcomes in extracorporeal life support.
AB  - The Extracorporeal Life Support Organization Registry has collected outcome data
      of almost 56,000 patients receiving extracorporeal life support (ECLS) over the
      last 24 years. The use of neonatal respiratory ECLS declined from a peak of 1516
      cases in 1992 to 750-865 cases from 2008 to 2012. The 26,583 cases of neonatal
      respiratory ECLS (75% survival) represent the largest patient population in the
      registry. Indicating the rapid growth in other patient populations, 2013 marks
      the first year where the number of neonatal respiratory ECLS cases is less than
      50% of the registry. Stagnant at ~200 cases/year from 1993 to 2004, growth is
      occurring in the use of pediatric respiratory ECLS with 331-448 cases/year from
      2008 to 2012 (58% survival). Similarly, adult respiratory ECLS use increases have
      been seen from ~100 cases/year from 1996 to 2007 to 480-846 cases/year from 2009
      to 2012 (58% survival). Just over 15,000 cardiac ECLS patients have survival
      rates of 40%, 49%, and 40% for neonates, pediatric, and adults, respectively. 

PMID- 24580762
TI  - Venoarterial versus venovenous ECMO for neonatal respiratory failure.
AB  - Extracorporeal membrane oxygenation (ECMO) continues to be an important rescue
      therapy for newborns with a variety of causes of cardio-respiratory failure
      unresponsive to high-frequency ventilation, surfactant replacement, and inhaled
      nitric oxide. There are approximately 800 neonatal respiratory ECMO cases
      reported annually to the Extracorporeal Life Support Organization; venoarterial
      ECMO has been used in approximately 72% with a cumulative survival of 71% and
      venovenous has been used in 28% with a survival of 84%. Congenital diaphragmatic
      hernia is now the most common indication for ECMO. This article reviews the
      development of the two types of extracorporeal support, venoarterial and
      venovenous ECMO, and discusses the advantages of each method, the current
      selection criteria, the procedure, and the clinical management of neonates on
      ECMO. 

PMID- 24580764
TI  - Congenital diaphragmatic hernia: treatment and outcomes.
AB  - Congenital diaphragmatic hernia (CDH) is a congenital defect in the diaphragm
      that allows herniation of abdominal contents into the fetal chest and leads to
      varying degrees of pulmonary hypoplasia and pulmonary hypertension. Advances in
      prenatal diagnosis and the institution of standardized delivery and postnatal
      care protocols have led to improved survival. Fetal endoscopic tracheal occlusion
      shows early promise for patients with the most severe CDH, but prospective
      randomized data is still required. CDH survivors have a variety of associated
      morbidities that require long-term follow-up and early intervention strategies
      for optimal care. 

PMID- 24580765
TI  - Extracorporeal life support for the neonatal cardiac patient: outcomes and new
      directions.
AB  - Extracorporeal life support is an important therapy for neonates with life
      threatening cardiopulmonary failure. Utilization of extracorporeal life support
      in neonates with congenital heart disease has increased dramatically during the
      past three decades. Despite increased usage, overall survival in these patients
      has changed very little and extracorporeal life support-related morbidity,
      including bleeding, neurologic injury, and renal failure, remains a major
      problem. Although survival is lower and neurologic complications are higher in
      premature infants than term infants, cardiac extracorporeal life support
      including extracorporeal cardiopulmonary resuscitation is effective in preventing
      death in many of these high-risk patients. Miniaturized ventricular assist
      devices and compact integrated extracorporeal life support systems are being
      developed to provide additional therapeutic options for neonates. 

PMID- 24580766
TI  - ECMO in neonates: neuroimaging findings and outcome.
AB  - Extracorporeal membrane oxygenation (ECMO) is a rescue therapy for newborns with
      severe but reversible respiratory failure. Although ECMO has significantly
      improved survival, it is associated with substantial complications, of which
      intracranial injuries are the most important. These injuries consist of
      hemorrhagic and non-hemorrhagic, ischemic lesions. Different from the classical
      presentation of hemorrhages in preterm infants, hemorrhages in ECMO-treated
      newborns are mainly parenchymal and with a high percentage in the posterior fossa
      area. There are conflicting data on the predominant occurrence of cerebral
      lesions in the right hemisphere. The existence of intracerebral injuries and the
      classification of its severity are the major predictors of neurodevelopmental
      outcome. This section will discuss the known data on intracranial injury in the
      ECMO population and the effect of ECMO on the brain. 

PMID- 24580767
TI  - Long-term outcome of children treated with neonatal extracorporeal membrane
      oxygenation: increasing problems with increasing age.
AB  - As more and more critically ill neonates survive, it becomes important to
      evaluate long-term morbidity. This review aims to provide an up-to-date overview
      of medical and neurodevelopmental outcomes in children who as neonates received
      treatment with extracorporeal membrane oxygenation (ECMO). Most patients-except
      those with congenital diaphragmatic hernia-have normal lung function and normal
      growth at older age. Maximal exercise capacity is below normal and seems to
      deteriorate over time in the CDH population. Gross motor function problems have
      been reported until school age. Although mental development is usually favorable
      within the first years and cognition is normal at school age, many children
      experience problems with working speed, spatial ability tasks, and memory. In
      conclusion, children who survived neonatal treatment with ECMO often encounter
      neurodevelopmental problems at school age. Long-term follow-up is needed to
      recognize problems early and to offer appropriate intervention. 

PMID- 24580768
TI  - ECLS for preemies: the artificial placenta.
AB  - The high mortality and morbidity associated with respiratory failure among
      extremely low gestational age newborns (ELGANs) remains an unsolved problem. A
      logical strategy to avoid these complications would involve re-creating the
      intrauterine environment with extracorporeal membrane oxygenation (ECMO) instead
      of mechanical ventilation. Such a device, termed an artificial placenta, was
      first researched over 50 years ago. AP models vary, but all incorporate ECMO
      involving the umbilical vessels, lack of mechanical ventilation, and low partial
      pressure of oxygen to preserve fetal circulation. Current research has focused on
      low-volume pumpless arteriovenous circuits as well as pump-driven venovenous
      circuits. 

PMID- 24580769
TI  - Ethnoveterinary study of medicinal plants in Malakand Valley, District Dir
      (Lower), Khyber Pakhtunkhwa, Pakistan.
AB  - BACKGROUND: The Malakand valley of District Dir (Lower) is endowed with a diverse
      plant wealth. Ethnoveterinary knowledge provides the traditional medicines of
      livestock that are cheaper than standard treatment and are easily accessible.
      METHODS: The present study was conducted to document the traditional knowledge of
      ethnoveterinary practices in Malakand valley, District Dir (Lower). Data was
      collected from February 2012 to January 2013 by interviewing 120 inhabitants
      through semi-structured questionnaires. Different questions were asked to collect
      appropriate data regarding the use of plants for livestock treatment. Direct
      matrix ranking (DMR) was carried out to find out the use diversity of medicinal
      plants. FINDINGS: A total of 28 plants belonging to 23 families were collected
      and identified for the treatment of livestock in the study area. Majority of the
      plants were collected from wild (68%) habitat and very few from cultivated
      sources. The leaves (28%) were identified as the major plant part for herbal
      preparations. The most frequent ailments of livestocks in the study area were
      stomach disorders and Charmaikh (local disease name). Various ingredients were
      used along with ethnoveterinary medicines i.e. sugar, flour, milk etc. The elder
      people of the village had a rich knowledge as compared to the young generation.
      According to DMR output, Monotheca buxifolia ranked first and Dalbergia sisso and
      Melia azedarach ranked second due to high multipurpose uses among all species and
      was found most threatened in the study area. CONCLUSION: It has been concluded
      that the native of the region heavily dependent on medicinal plants for the
      treatment of variety of livestock ailments. Traditional knowledge always provides
      a baseline for further phytochemical and pharmacological investigation. The
      documentation of the ethnoveterinary practices in study area was necessary before
      this precious knowledge is lost forever due to rapid socioeconomic, environmental
      and technological changes.

PMID- 24580770
TI  - Anti-inflammatory effects of resolvin-D1 on human corneal epithelial cells: in
      vitro study.
AB  - BACKGROUND: This study evaluated the anti-inflammatory effects of Resolvin-D1 (RV
      D1) and its mechanism of action in human corneal epithelial (HCE) cells. METHODS:
      HCE cells were incubated with different concentrations of RV-D1 for different
      time periods. Oleic acid (OA) and Dexamethasone (DM) served as negative and
      positive controls, respectively. Cells were stimulated with
      polyriboinosinic:polyribocytidylic acids (poly I:C). The protein contents and
      mRNA expression levels of Tumor necrosis factor-alpha (TNF-alpha), Interleukin
      (IL)-6, IL-1beta and IL-8 were evaluated with multiplex fluorescent bead
      immunoassay (FBI) and real time-PCR, respectively. In addition, the expression of
      inhibitory factor-kappaBalpha (I-kappaBalpha) was evaluated with real time-PCR.
      RESULTS: The protein level of pro-inflammatory cytokines TNF-alpha, IL-6, IL
      1beta and IL-8 significantly increased after stimulation with Poly I:C. RV-D1
      treatment at concentration of 1 MUM decreased the protein level of TNF-alpha to
      20.76 +/- 9.3% (P < 0.05), IL-6 to 43.54 +/- 14.16% (P < 0.001), IL-1beta to
      46.73 +/- 15.93% (P > 0.05) and IL-8 to 51.15 +/- 13.01% (P < 0.05) compared with
      cells stimulated with poly I:C alone. Similarly, the mRNA levels of TNF-alpha, IL
      6, IL-1beta and IL-8 were significantly reduced after treatment with RV-D1. A
      highly significant dose response curve was demonstrated for RV-D1 treated HCE
      cells for TNF-alpha and IL-1beta.DM treatment decreased the protein content for
      all of the pro-inflammatory cytokines, similar results were demonstrated at the
      mRNA level. The anti-inflammatory effects of RV-D1 were similar to those of DM
      for TNF-alpha, IL-6 and IL-8. CONCLUSIONS: RV-D1 may serve as a potent anti
      inflammatory agent in ocular surface inflammation, as evaluated in cultured HCE
      cells. The anti-inflammatory effects of RV-D1 were comparable to those of DM, and
      were mediated through nuclear factor kappa B (NF-kappaB) signal transduction.

PMID- 24580763
TI  - Update on PPHN: mechanisms and treatment.
AB  - Persistent pulmonary hypertension of the newborn (PPHN) is a syndrome of failed
      circulatory adaptation at birth, seen in about 2/1000 live born infants. While it
      is mostly seen in term and near-term infants, it can be recognized in some
      premature infants with respiratory distress or bronchopulmonary dysplasia. Most
      commonly, PPHN is secondary to delayed or impaired relaxation of the pulmonary
      vasculature associated with diverse neonatal pulmonary pathologies, such as
      meconium aspiration syndrome, congenital diaphragmatic hernia, and respiratory
      distress syndrome. Gentle ventilation strategies, lung recruitment, inhaled
      nitric oxide, and surfactant therapy have improved outcome and reduced the need
      for extracorporeal membrane oxygenation (ECMO) in PPHN. Newer modalities of
      treatment discussed in this article include systemic and inhaled vasodilators
      like sildenafil, prostaglandin E1, prostacyclin, and endothelin antagonists. With
      prompt recognition/treatment and early referral to ECMO centers, the mortality
      rate for PPHN has significantly decreased. However, the risk of potential
      neurodevelopmental impairment warrants close follow-up after discharge for
      infants with PPHN. 

PMID- 24580771
TI  - Prevalence, incidence and risk factors for donor-specific anti-HLA antibodies in
      maintenance liver transplant patients.
AB  - Although large retrospective studies have identified the presence of donor
      specific antibodies (DSAs) to be a risk factor for rejection and impaired
      survival after liver transplantation, the long-term predicted pathogenic
      potential of individual DSAs after liver transplantation remains unclear. We
      investigated the incidence, prevalence and consequences of DSAs in maintenance
      liver transplant (LT) recipients. Two hundred sixty-seven LT recipients, who had
      undergone transplantation at least 6 months previously and had been screened for
      DSAs at least twice using single-antigen bead technology, were included and
      tested annually for the presence of DSAs. At a median of 51 months (min-max: 6
      220) after an LT, 13% of patients had DSAs. At a median of 36.5 months (min-max:
      2-45) after the first screening, 9% of patients have developed de novo DSAs. The
      sole predictive factor for the emergence of de novo DSAs was retransplantation
      (OR 3.75; 95% CI 1.28-11.05, p = 0.025). Five out of 21 patients with de novo
      DSAs (23.8%) developed an antibody-mediated rejection. Fibrosis score was higher
      among patients with DSAs. In conclusion, monitoring for the development of DSAs
      in maintenance LT patients is useful in case of graft dysfunction and to identify
      patients with a high risk of developing liver fibrosis.

PMID- 24580772
TI  - Mitochondrial genome of Babesia orientalis, apicomplexan parasite of water
      buffalo (Bubalus babalis, Linnaeus, 1758) endemic in China.
AB  - BACKGROUND: Apicomplexan parasites of the genus Babesia, Theileria and Plasmodium
      are very closely related organisms. Interestingly, their mitochondrial (mt)
      genomes are highly divergent. Among Babesia, Babesia orientalis is a new species
      recently identified and specifically epidemic to the southern part of China,
      causing severe disease to water buffalo. However, no information on the mt genome
      of B. orientalis was available. METHODS: Four pairs of primers were designed
      based on the full genome sequence of B. orientalis (unpublished data) and by
      aligning reported mt genomes of B. bovis, B. bigemina, and T. parva. The entire
      mt genome was amplified by four sets of PCR. The obtained mt genome was annotated
      by aligning with published apicomplexan mt genomes and Artemis software v11.
      Phylogenetic analysis was performed by using cox1 and cob amino acid sequences.
      RESULTS: The complete mt genome of B. orientalis (Wuhan strain) was sequenced and
      characterized. The entire mt genome is 5996 bp in length with a linear form,
      containing three protein-coding genes including cytochrome c oxidase I (cox1),
      cytochrome b (cob) and cytochrome c oxidase III (cox3) and six rRNA large subunit
      gene fragments. The gene arrangement in B. orientalis mt genome is similar to
      those of B. bovis, B. gibsoni and Theileria parva, but different from those of T.
      orientalis, T. equi and Plasmodium falciparum. Comparative analysis indicated
      that cox1 and cob genes were more conserved than cox3. Phylogenetic analysis
      based on amino acid sequences of cox1, cob and cox1 + cob, respectively, revealed
      that B. orientalis fell into Babesia clade with the closest relationship to B.
      bovis. CONCLUSIONS: The availability of the entire mt genome sequences of B.
      orientalis provides valuable information for future phylogenetic, population
      genetics and molecular epidemiological studies of apicomplexan parasites.

PMID- 24580775
TI  - Recommended dietary intakes for vitamin D: Where do they come from, what do they
      achieve and how can we meet them?
AB  - There is substantial evidence that the prevalence of vitamin D deficiency is high
      across Europe, particularly, but not exclusively, among those resident at
      Northerly latitudes. This has significant implications for human health
      throughout the lifecycle and impacts upon healthy growth and development and
      successful ageing for current and possibly future generations. In recent years,
      there have been several important reports from North America and Europe in
      relation to dietary reference values (DRVs) for vitamin D. These may be of
      enormous value from a public health perspective in terms of preventing vitamin D
      deficiency and promoting adequate vitamin D status in the population. In this
      concise review, we provide a brief summary of current DRVs for vitamin D, their
      background and their application to vitamin D deficiency prevention. The review
      also provides some brief guidance with respect to applying the DRVs in a clinical
      nutrition setting. In addition, the review illustrates how current dietary
      intakes of most populations, young and adult, are well short of the newly
      established DRVs. Accordingly, the review highlights potential food-based or
      dietary strategies for increasing the distribution of vitamin D intake in the
      population with the aim of preventing vitamin D deficiency. Finally, despite the
      explosion in scientific research in vitamin D and health, there are many
      fundamental gaps in the field of vitamin D from the public health perspective.
      The impact of these knowledge gaps on current DRVs for vitamin D is highlighted,
      as are some future developments that may help address these gaps. 

PMID- 24580774
TI  - Meta-analysis of the effect of percutaneous coronary intervention on chronic
      total coronary occlusions.
AB  - BACKGROUND AND PURPOSE: Coronary chronic total occlusion (CTO) is the last stage
      of coronary artery atherosclerosis. Percutaneous coronary intervention (PCI) is a
      therapeutic procedure used to recanalize vessels with total occlusion. However,
      successful recanalization of CTO is still not optimal, and the key influence
      factors are still uncertainty. Therefore, a scientific evaluation on the
      effective of PCI for CTO treatment is necessary. METHODS: Relevant studies of PCI
      treatment for CTO were examined. Data were extracted and assessed by two
      independent clinical experts. Embase, PubMed and Medline et al. were used as
      database. The main research key words include "CTO", "PCI", "Stent", "Reopen",
      "long-term", "follow-up" and "outcome". Quality assessment was carried out
      according to the Cochrane Handbook. The selected data were pooled and analyzed
      using fixed-effect model and random-effect model. Heterogeneity was assessed
      using the I(2) test, Q test, L'abbe and Galbraith. Comprehensive Meta -Analysis
      2.0 and Metanalysis 1.0 were used for statistics analysis in this research.
      RESULTS: A total of 16 articles involving 6695 cases in successful CTO
      recanalization (CTO success group) and 2370 cases in failed CTO
      recanalization(CTO failure group) were included in this research. Low CTO success
      was associated with elder age, previous coronary artery bypass graft surgery
      (CABG) history, multi-vessel diseases and right coronary artery disease lesion.
      Six follow-up variables including major adverse cardiac events (MACE), recurrent
      myocardial infarction (MI), all-cause death, incidence of angina, subsequent CABG
      and cumulative survival rate were found significantly reduced associated with CTO
      success. CONCLUSIONS: Clinical baseline characteristics such as age, previous
      CABG history and lesion baseline characteristics such as lesion length, multi
      vessel diseases might be important factors influencing the successful rate of CTO
      recanalization. Compared to CTO failure patients, all six follow-up variables
      showed advantage for CTO success patients.

PMID- 24580773
TI  - The informed consent in Southern Italy does not adequately inform parents about
      infant vaccination.
AB  - BACKGROUND: Vaccination centres in the Campania Region, southern Italy, vaccinate
      children with a hexavalent vaccine that contains the mandatory vaccines
      diphtheria, tetanus, poliomyelitis, and viral Hepatitis B. This vaccine also
      includes two non-mandatory vaccines, pertussis and Haemophilus influenzae type B.
      Information about these optional vaccines should be communicated to the parents,
      and informed consent should be obtained from parents before vaccination. We
      explored whether informed consent was delivered to the parents, whether they
      signed the consent form, and whether they read and acquired the information about
      the vaccination that their child would receive. METHODS: Childhood immunisations
      are provided at specific public health vaccination centres, "Unita Operative
      Materno-infantili's" (UOMIs). We selected four UOMI from the Campania Region
      where we interviewed 1039 parents bringing their children for the 1st, 2nd, or
      3rd doses of hexavalent vaccine. The consent forms were collected from the four
      vaccination centres and were analysed with respect to clarity and completeness.
      RESULTS: Most of the respondents (89.5%) were mothers between 20 and 39 years of
      age (80.4% vs 59.6% of the fathers), they were married (87.2% vs 93.5% of the
      fathers), and only one-half of them were employed (50.2% vs 92.6% of the
      fathers). The informed consent form was received from 58.1% of the parents and
      signed by 52.8%, but read by 35.0% of them. Only 1.5% of parents knew which
      vaccines were mandatory, and 25.0% of them believed that the entire hexavalent
      vaccine was mandatory. When we asked the parents which non-mandatory vaccinations
      were administered to their children, only 0.5% indicated the Haemophilus
      influenzae type B and none indicated the pertussis vaccine. Thirty-six per cent
      of the parents replied that their child had not received any non-mandatory
      vaccines. No parents were informed by the operators that their children would
      receive non-mandatory vaccines. CONCLUSION: In our study, consent procedures did
      not allow parents to acquire correct information about vaccine options for their
      children. Furthermore, not one health care provider informed parents that their
      child was receiving non-mandatory vaccines. The informed consent process and the
      individual health care providers did not properly inform parents about the
      vaccines administered to their children.

PMID- 24580777
TI  - Multiple hepatitis C virus (HCV) reinfections in HIV-positive men who have sex
      with men: no influence of HCV genotype switch or interleukin-28B genotype on
      spontaneous clearance.
AB  - OBJECTIVES: The incidence of sexually transmitted hepatitis C virus (HCV)
      reinfection is on the rise in HIV-infected men who have sex with men (MSM). Data
      on natural history of acute hepatitis C and possible factors associated with
      spontaneous clearance are limited. The aim of this study was to analyse the
      outcome of HCV reinfections in HIV-positive MSM. METHODS: A retrospective
      analysis was carried out on patients with more than one sexually acquired HCV
      infection who were diagnosed at four major German HIV and hepatitis care centres.
      Reinfection was defined by genotype or phylogenetic clade switch, detectable HCV
      RNA after a sustained virological response (SVR) or after spontaneous clearance
      (SC). RESULTS: In total, 48 HIV-positive MSM were identified with HCV
      reinfection, among them 11 with a third episode and one patient with four
      episodes. At the first episode, 43 and five patients had an SVR and SC,
      respectively. The second episode was accompanied by a genotype switch in 29
      patients (60%). Whereas 30 and nine patients showed an SVR and SC, respectively,
      eight patients developed chronic hepatitis. Neither HCV genotype switch nor
      interleukin-28B genotype was associated with SC. However, SC rates at the second
      episode were higher for patients with SC at the first episode compared with
      patients without SC (60 vs. 14%, respectively; P = 0.03). Two patients with SC at
      the first episode were reinfected with the same genotype. CONCLUSIONS: Multiple
      reinfections in HIV-infected MSM do occur, with or without genotype switch, and
      with prior SC of previous episodes. In this large case series, except for SC at
      the first episode, no factor was of value in clinical decision-making for early
      therapeutic intervention in acute HCV reinfection.

PMID- 24580776
TI  - Stability SCAD: a powerful approach to detect interactions in large-scale genomic
      study.
AB  - BACKGROUND: Evidence suggests that common complex diseases may be partially due
      to SNP-SNP interactions, but such detection is yet to be fully established in a
      high-dimensional small-sample (small-n-large-p) study. A number of penalized
      regression techniques are gaining popularity within the statistical community,
      and are now being applied to detect interactions. These techniques tend to be
      over-fitting, and are prone to false positives. The recently developed stability
      least absolute shrinkage and selection operator (SLASSO) has been used to control
      family-wise error rate, but often at the expense of power (and thus false
      negative results). RESULTS: Here, we propose an alternative stability selection
      procedure known as stability smoothly clipped absolute deviation (SSCAD).
      Briefly, this method applies a smoothly clipped absolute deviation (SCAD)
      algorithm to multiple sub-samples, and then identifies cluster ensemble of
      interactions across the sub-samples. The proposed method was compared with SLASSO
      and two kinds of traditional penalized methods by intensive simulation. The
      simulation revealed higher power and lower false discovery rate (FDR) with SSCAD.
      An analysis using the new method on the previously published GWAS of lung cancer
      confirmed all significant interactions identified with SLASSO, and identified two
      additional interactions not reported with SLASSO analysis. CONCLUSIONS: Based on
      the results obtained in this study, SSCAD presents to be a powerful procedure for
      the detection of SNP-SNP interactions in large-scale genomic data.

PMID- 24580779
TI  - Care for post-stroke patients at Malaysian public health centres: self-reported
      practices of family medicine specialists.
AB  - BACKGROUND: Provision of post stroke care in developing countries is hampered by
      discoordination of services and limited access to specialised care. Albeit
      shortcomings, primary care continues to provide post-stroke services in less than
      favourable circumstances. This paper aimed to review provision of post-stroke
      care and related problems among Family Medicine Specialists managing public
      primary health care services. METHODS: A semi-structured questionnaire was
      distributed to 121 Family Physicians servicing public funded health centres in a
      pilot survey focused on improving post stroke care provision at community level.
      The questionnaire assessed respondents background and practice details i.e.
      estimated stroke care burden, current service provision and opinion on service
      improvement. Means and frequencies described quantitative data. For qualitative
      data, constant comparison method was used until saturation of themes was reached.
      RESULTS: Response rate of 48.8% was obtained. For every 100 patients seen at
      public healthcentres each month, 2 patients have stroke. Median number of stroke
      patients seen per month is 5 (IQR 2-10). 57.6% of respondents estimated total
      stroke patients treated per year at each centre was less than 40 patients. 72.4%
      lacked a standard care plan although 96.6% agreed one was needed. Patients seen
      were: discharged from tertiary care (88.1%), shared care plan with specialists
      (67.8%) and patients who developed stroke during follow up at primary care
      (64.4%). Follow-ups were done at 8-12 weekly intervals (60.3%) with 3.4% on 'as
      needed' basis. Referrals ranked in order of frequency were to physiotherapy
      services, dietitian and speech and language pathologists in public facilities.
      The FMS' perceived 4 important 'needs' in managing stroke patients at primary
      care level; access to rehabilitation services, coordinated care between tertiary
      centres and primary care using multidisciplinary care approach, a standardized
      guideline and family and caregiver support. CONCLUSIONS: Post discharge stroke
      care guidelines and access to rehabilitation services at primary care is needed
      for post stroke patients residing at home in the community.

PMID- 24580778
TI  - In vivo antimalarial activity of the crude leaf extract and solvent fractions of
      Croton macrostachyus Hocsht. (Euphorbiaceae) against Plasmodium berghei in mice.
AB  - BACKGROUND: The issue of resistance in malarial infection makes development of
      novel drugs a necessity. An alternative source for discovering such drugs is
      natural products. Croton macrostachyus H. (Euphorbiaceae) is used in Ethiopian
      folklore medicine for the treatment of malaria and found to possess antimalarial
      activity in vitro. However, no further scientific investigations have been
      carried out to substantiate the claim. This study therefore aimed at
      investigating the in vivo antiplasmodial activity of 80% methanol extract and
      solvent fractions of the leaves of Croton macrostachyus H. in rodent model of
      malaria. METHODS: A rodent malaria parasite, Plasmodium berghei, was used to
      inoculate healthy male Swiss Albino mice of age 6-8 weeks and weight 23-27 g. A
      hydro-alcoholic crude extract and the solvent fractions (chloroform, methanol and
      aqueous) were administered at different doses 200, 400 and 600 mg/kg. Parameters,
      including parasitemia, survival time, body weight, temperature, and packed cell
      volume were then determined using standard tests such as Peter's and Rane's test.
      RESULTS: Chemoprotective effect exerted by the crude extract and fractions ranged
      between 44-91% and 12-76%, respectvely. The chemotherapeutic effect of the crude
      extract and chloroform fraction was in the range of 39-83% and 66-82%,
      respectively. Maximum effect in both tests was observed with the larger dose of
      the crude extract and chloroform fraction. The crude extract prevented loss of
      weight and reduction in temperature but did not affect packed cell volume.
      However, the chloroform fraction did also reverse reduction in packed cell volume
      due to the absence of saponins in the fraction. CONCLUSIONS: The results
      collectively indicate that the plant has a promising antiplasmodial activity
      against Plasmodium berghei, which upholds the earlier in vitro findings as well
      as its folkloric use. Thus, it could be considred as a potential source to
      develop new antimalarial agents.

PMID- 24580781
TI  - Editorial: representations of sexuality: a snapshot of 5 years of scholarship in
      the Journal of Clinical Nursing.

PMID- 24580782
TI  - Editorial: sexual health: an integral part of our health and quality of life.

PMID- 24580780
TI  - Direct measurement of transcription rates reveals multiple mechanisms for
      configuration of the Arabidopsis ambient temperature response.
AB  - BACKGROUND: Sensing and responding to ambient temperature is important for
      controlling growth and development of many organisms, in part by regulating mRNA
      levels. mRNA abundance can change with temperature, but it is unclear whether
      this results from changes in transcription or decay rates, and whether passive or
      active temperature regulation is involved. RESULTS: Using a base analog labelling
      method, we directly measured the temperature coefficient, Q10, of mRNA synthesis
      and degradation rates of the Arabidopsis transcriptome. We show that for most
      genes, transcript levels are buffered against passive increases in transcription
      rates by balancing passive increases in the rate of decay. Strikingly, for
      temperature-responsive transcripts, increasing temperature raises transcript
      abundance primarily by promoting faster transcription relative to decay and not
      vice versa, suggesting a global transcriptional process exists that controls mRNA
      abundance by temperature. This is partly accounted for by gene body H2A.Z which
      is associated with low transcription rate Q10, but is also influenced by other
      marks and transcription factor activities. CONCLUSIONS: Our data show that less
      frequent chromatin states can produce temperature responses simply by virtue of
      their rarity and the difference between their thermal properties and those of the
      most common states, and underline the advantages of directly measuring
      transcription rate changes in dynamic systems, rather than inferring rates from
      changes in mRNA abundance.

PMID- 24580783
TI  - Women's understandings of sexual problems: findings from an in-depth interview
      study.
AB  - AIMS AND OBJECTIVES: To explore women's understandings of sexual problems.
      BACKGROUND: Prevailing knowledge about women's sexual problems has prioritised
      the material body. Particular attention is given to the importance of penetrative
      sexual intercourse, orgasm and the reproductive imperative, which fail to take
      account of contextual factors that contribute to women's experiences of sexual
      problems. DESIGN: Qualitative in-depth interview study. METHODS: Individual in
      depth interviews conducted with 23 women aged 23-72 years, recruited from members
      of the general public and a psychosexual clinic. RESULTS: The findings suggest
      that sexual problems are bodily experienced and socially and psychologically
      mediated. Women's views were influenced by the relational context of their
      experiences. At the same time, their views were deeply embedded within a
      patriarchal framework to make sense of their own sexual functioning and
      satisfaction. CONCLUSION: This study presents a challenge in the drive to
      medicalise women's sexual problems via the female sexual dysfunction label. It
      problematises the current diagnostic criteria for sexual problems outlined in the
      Diagnostic and Statistical Manual, which presupposes a highly individualised
      framework and favours a more nuanced approach. RELEVANCE TO CLINICAL PRACTICE:
      Rather than adopting or eschewing an entirely medical or psychosocial model,
      women presenting with sexual problems should be seen by a clinician whose
      assessment is holistic and takes into account relational, cultural, psychosocial
      and health-related concerns.

PMID- 24580785
TI  - Young Singaporean women's knowledge of cervical cancer and pap smear screening: a
      descriptive study.
AB  - AIMS AND OBJECTIVES: To assess the knowledge of young female Singaporeans
      regarding cervical cancer and pap smear, the intention to participate in pap
      smear and whether there is any relationship between knowledge and intention to
      participate in pap smear screening. BACKGROUND: While cervical cancer has poor
      prognosis in the later stages, pap smear is effective in identifying precancerous
      lesions, which are more treatable. Pap smear screening is available to women in
      Singapore, but its uptake is opportunistic. Research has shown that knowledge
      about pap smear and cervical cancer is important determinant of screening
      behaviour in Singaporean women. DESIGN: Cross-sectional descriptive correlational
      design was used. METHODS: Three hundred and ninety-three young Singaporean
      undergraduates, aged 18-25 years, were recruited via convenience sampling from a
      local university over a four-month period. Data were collected through self
      administered questionnaires. RESULTS: Majority of the participants knew the term
      'pap smear' and its function. However, knowledge of the risk factors for cervical
      cancer was lacking among the young women. Knowledge of pap smear and cervical
      cancer had a weak correlation with the intention to go for the future uptake of
      pap smear. CONCLUSIONS: Educational efforts among younger Singaporean women on
      the knowledge of pap smear and risk factors for cervical cancer are needed.
      Improving knowledge will enable them to understand the importance of reducing
      exposure to risk factors and regular pap smear screening. RELEVANCE TO CLINICAL
      PRACTICE: All health professionals working with young Asian women should be
      prepared to educate and counsel young women to participate in pap smear screening
      according to current guidelines. In particular, knowledge of the age to attend
      the first pap smear and the recommended frequency for screening need to be
      targeted for health education.

PMID- 24580784
TI  - Sexual risk factors for partner age discordance in adolescent girls and their
      male partners.
AB  - AIMS AND OBJECTIVES: To investigate differences in sexual risk factors between
      adolescent girls reporting similar-aged or older sex partners. BACKGROUND:
      Adolescent girls are at significant risk of heterosexual-acquired HIV infection
      and other long-term reproductive health issues. Sexual partner age discordance in
      teen girls has been correlated with STIs, lack of protection, multiple partners
      and earlier age of sexual transition. DESIGN: A descriptive study comparing girls
      currently involved with age-discordant partners to those with similar-aged
      partners. Two-sample t-test for continuous variables and chi-squared test or
      Fisher's exact test for categorical variables were used to compare groups.
      METHODS: Baseline data from 738 sexually active, urban, adolescent girls aged 15
      19 were analysed to determine which behaviours were more likely to occur in girls
      with older partners. Data were collected as part of a gender-specific HIV
      prevention intervention in a randomised controlled trial (RCT) tailored to
      adolescent girls. RESULTS: Multiple reported sexual risk behaviours were found to
      significantly differ between the two groups at baseline. Overall, girls with
      older partners had more episodes of sexual instances (vaginal, anal and oral).
      Specific sexual risk behaviours were found to be statistically significant
      between the two groups. Girls with older partners started having sex at earlier
      ages, had more lifetime sexual partners, higher incidents of STIs and were
      reluctant to discuss using condoms with their partners. Girls with similar-aged
      partners were less willing to engage in risky sexual behaviours. CONCLUSIONS:
      Findings from this investigation support data from other studies. Relationships
      with older male partners place adolescent girls at increased risk of HIV/STIs and
      unintended pregnancy. RELEVANCE TO CLINICAL PRACTICE: Adolescent girls in age
      discordant relationships are at risk of immediate and long-term sexual health
      morbidities. Identifying girls who are at increased risk by asking tailored
      questions will enable nurses to recommend appropriate diagnostics for this
      population and provide age-specific counselling.

PMID- 24580786
TI  - A cross-sectional study of the beliefs and attitudes towards menstruation of
      Chinese undergraduate males and females in Hong Kong.
AB  - AIMS AND OBJECTIVES: To explore the beliefs and attitudes towards menstruation of
      Chinese undergraduates in Hong Kong and to compare those of (1) male and female
      undergraduates with those of (2) undergraduates studying health-related vs.
      nonhealth-related programmes. BACKGROUND: Menstruation is typically viewed as a
      forbidden topic or a troublesome experience. These negative beliefs and attitudes
      result from existing myths and taboos associated with cultural factors and health
      education levels. DESIGN: A cross-sectional survey was conducted in all
      universities in Hong Kong. Undergraduates were invited through convenience
      sampling to complete a questionnaire assessing their attitudes and beliefs
      towards menstruation. METHODS: A questionnaire on 'beliefs about and attitudes
      towards menstruation' was adopted. Questionnaires were self-administered by the
      respondents. RESULTS: A total of 450 questionnaires were distributed, and a
      response rate of 96.6% was obtained; 416 completed questionnaires were collected
      and analysed. Many Chinese undergraduates agreed that menstruation is annoying,
      causes disability, involves prescription and proscription and is not pleasant.
      When comparing the beliefs and attitudes towards menstruation of Chinese male
      undergraduates with those of female undergraduates, females tended to disagree
      that menstruation should be maintained secret, but tended to agree that it was
      annoying. When comparing the beliefs and attitudes towards menstruation of
      Chinese undergraduates studying health-related programmes with those under
      nonhealth-related programmes, the latter group exhibited a higher level of belief
      in prescription and proscription for menstruation than the former group.
      CONCLUSION: Chinese undergraduates in Hong Kong were influenced by the
      traditional Chinese culture and social environment, resulting in negative
      attitudes towards menstruation. This study recommends that sex education,
      especially reproductive health education, be extended to tertiary education.
      RELEVANCE TO CLINICAL PRACTICE: This study provides relevant information on
      planning the content of sex education or reproductive health education for
      Chinese undergraduates.

PMID- 24580787
TI  - Tertiary paediatric hospital health professionals' attitudes to lesbian, gay,
      bisexual and transgender parents seeking health care for their children.
AB  - AIMS AND OBJECTIVES: To ascertain health professionals' knowledge, attitudes and
      beliefs towards lesbian, gay, bisexual and transgender parents seeking health
      care for their children in a paediatric tertiary hospital setting which practises
      family-centred care. BACKGROUND: Lesbian, gay, bisexual and transgender parents
      are often reluctant to disclose their sexual orientation to health professionals
      for fear of discrimination and compromised quality of care. Staff knowledge,
      attitudes and beliefs can influence disclosure by parents, but little is known
      about knowledge, attitudes and beliefs in paediatric tertiary hospital staff
      towards lesbian, gay, bisexual and transgender parents accessing care for their
      children. DESIGN: Descriptive comparative study of health staff using a cross
      sectional survey. METHODS: A set of validated anonymous questionnaires was used
      to assess knowledge about homosexuality, attitudes towards lesbians and gay men,
      and gay affirmative practice. Three open-ended questions were also used to assess
      beliefs about encouraging disclosure of lesbian, gay, bisexual and transgender
      parenting roles and how this may impact on care. RESULTS: Of the 646 staff
      surveyed, 212 (32.8%) responded. Knowledge and attitudes were significantly
      associated with professional group, gender, Caucasian race, political voting
      behaviour, presence of religious beliefs, the frequency of attendance at
      religious services, the frequency of praying, and having a friend who was openly
      lesbian, gay, bisexual and transgender. CONCLUSION: This study highlighted that
      staff working in a tertiary paediatric hospital setting, with family-centred care
      models in place, held attitudes and beliefs that may impact on the experience of
      hospitalisation for lesbian, gay, bisexual and transgender parents, and the
      quality of care received by their children. RELEVANCE TO CLINICAL PRACTICE: To
      promote equitable care to all families, organisations should ensure that family
      centred care policies and guidelines are adopted and appropriately implemented.
      In addition to formal education, affirmative health service action and innovative
      methods may be required.

PMID- 24580788
TI  - Woman's contraceptive needs and preferences in the postpartum period: an Italian
      study.
AB  - AIMS AND OBJECTIVES: To describe what puerperal women know about postpartum
      contraception and to identify their related needs and expectations. BACKGROUND:
      Puerperal women face the problem of beginning or resuming contraception, the
      choice of the right method of contraception and the right time to start it. This
      choice becomes particularly important in case they breastfeed since the
      contraceptive method should not interfere with breastfeeding. Different factors,
      such as the level of knowledge women have about various contraceptive methods,
      their individual preferences or their desire to have a baby, can strongly
      influence this choice. DESIGN: A cross-sectional study had been carried out
      within the period of six months, from November 2011-February 2012. METHODS: Three
      hundred puerperal women were interviewed before their discharge from a Maternity
      Home. The women were asked for their personal characteristics, their maternity
      history, the information they had received, their knowledge and expectations
      about postpartum contraception and their intention to use contraception. RESULTS:
      During pregnancy and postpartum, 45.5% of the women reported that they had
      received adequate information about contraception. Of these ones, 64.3% reported
      their intention to use contraception either to avoid pregnancy or to space out
      future births, even if they did not always have appropriate knowledge about
      fertility and the use of contraceptive methods during postpartum. During this
      study, we also discovered that women's intention to use contraception was
      proportional to their level of education. CONCLUSION: Women need more and
      appropriate information about postpartum contraception, to make a conscious
      choice in relation to their needs and without putting their health at risk.
      RELEVANCE TO CLINICAL PRACTICE: To promote awareness of the choices related to
      postpartum contraception, it is important to understand the personal
      characteristics that influence or hinder this choice. Midwives can play a very
      important role in informing women and in developing educational interventions to
      support a safe contraceptive choice.

PMID- 24580789
TI  - Women's experiences of infertility - towards a relational model of care.
AB  - AIMS AND OBJECTIVES: To consider the effectiveness of current models of patient
      centred infertility care. BACKGROUND: Patient centredness is defined as one of
      six key dimensions of quality of care. In the field of infertility, a new
      interaction model of patient-centred infertility care is proposed. Despite
      positive moves, this model reveals shortcomings in knowledge about the lived
      experience of infertility and lacks the shift in attitudes and approach that
      effective patient-centred care requires. DESIGN: The study has a qualitative
      research design. Nine women living with and through infertility participated in
      online life-story interviews. METHODS: Data were analysed using a layered
      strategy influenced by the voice-centred relational method, emphasising narrative
      content, form and function. RESULTS: Women reveal a complex experience. Three key
      themes were found: Approaching the clinic narratives are infused with personal
      expectations while deeply reflective of cultural expectations and social norms.
      Relatedness recognises women's experiences cannot be neatly separated into
      distinct domains. Liminality and infertility describes women's experiences lost
      in transition through and beyond infertility treatment. CONCLUSIONS: The current
      model of patient-centred infertility care requires further development. Women in
      this study found themselves lost in transition and irrespective of treatment
      failure or success. Conceptual development must embrace a relational
      understanding of patient's experience to ensure that patient-centred infertility
      care is realistic and relevant to patients, clinical staff and the system as a
      whole. RELEVANCE TO CLINICAL PRACTICE: Psychosocial skills are recognised as core
      competences for fertility nurses. A relational conceptualisation of patient's
      experiences, living with and through infertility, provides further information
      for the development of staff and enhanced knowledge and practice skills.

PMID- 24580790
TI  - Investigating the sexual function and its associated factors in women with
      chronic illnesses.
AB  - AIMS AND OBJECTIVES: To evaluate sexual dysfunction and the factors that affect
      sexual dysfunction in women with chronic disease. BACKGROUND: Sexual dysfunction
      is one of the most common problems in women with chronic disease. There is
      limited understanding of the related factors of sexual dysfunction in women with
      chronic disease, with research currently limited to other problems and problems
      related to chronic diseases. DESIGN: This research was conducted as a descriptive
      survey. METHODS: This study involved 100 female inpatients at clinics of internal
      medicine of a university hospital. Data were collected with a patients
      identification form and a female sexual function index (KCFI). Kruskal-Wallis
      test, test of significance of difference between two means and test of
      significance of difference between two pairs were used in the data analysis.
      RESULTS: Sixty-five percentage of women in the sample were defined to have sexual
      dysfunction. The majority of women expressed pain during sexual intercourse,
      problems in orgasm and satisfaction, and reluctance to have sex. Older age, being
      unemployed, being in menopause, fatigue, sleep disorder, and pain and weakness in
      extremities were the factors that were found to significantly affect the
      prevalence of sexual dysfunction (p < 0.05). CONCLUSIONS: This study concluded
      that sexual function of women with chronic disease is affected negatively.
      Chronic disease-related symptoms, experienced changes in the body and
      psychosocial problems are changing the lives of women. Ultimately, these changes
      also affect sexual activity. RELEVANCE TO CLINICAL PRACTICE: Determination of the
      factors affecting sexual activity in women with chronic disease is important for
      women' ability to cope with sexual dysfunction and keep it under control. To be
      able to accomplish this, it is necessary for healthcare personnel, the partners
      and family to work together.

PMID- 24580791
TI  - Impaired sexual function and prostate cancer: a mixed method investigation into
      the experiences of men and their partners.
AB  - AIMS AND OBJECTIVES: To explore issues related to sexual function and
      relationships, for men and their wives or partners, following diagnosis and
      treatment for prostate cancer. BACKGROUND: A diagnosis of prostate cancer and
      subsequent treatment result in a significant number of men experiencing some
      impairment to their sexual function. There is scant research into the impact of
      changed sexual function on these men's masculinity, sexuality, intimate
      relationships and their needs regarding counselling and supportive care. DESIGN:
      Internet-based survey. METHODS: Focus groups and couple interviews were used to
      improve validity for questionnaire items designed to provide insight into men's
      experiences of prostate cancer in areas such as sexual function and
      relationships. The questionnaire included both closed and open-ended questions
      and had the option for the wife or partner to complete a section. RESULTS:
      Qualitative research revealed 17 specific categories within three key themes:
      sexual dysfunction, loss of libido and masculinity. The questionnaire found,
      unexpectedly, the majority of men said that they had sufficient emotional and
      psychological support. Wives/partners confirmed cancer had impacted on their
      partner's feelings of masculinity (71%), compared to 42% of men who felt that
      this was the case. Predictors of loss of libido, erectile dysfunction and
      'feeling less of a man' were developed. Univariate predictors included hormone
      therapy, regrets about treatment choice, cancer having impacted on masculinity
      and distress during the last week. CONCLUSIONS: Men are not able to clearly
      identify the challenges prostate cancer brings especially changes to their
      masculinity. RELEVANCE TO CLINICAL PRACTICE: The findings strongly suggest that
      for men with prostate cancer, nursing assessments of men's sexual health be
      augmented by information gained from their partners; further, these assessments
      should be augmented with a careful exploration of these men's psyche guided by
      the knowledge that masculinity influences perceptions of self (being a man) and
      help seeking.

PMID- 24580792
TI  - 'SI-SRH' - a new model to manage sexual health following a spinal cord injury:
      our experience.
AB  - AIMS AND OBJECTIVES: To maximise involvement of the multidisciplinary team using
      a model of sexual health management for spinal cord-injured persons. BACKGROUND:
      Regaining sexual function is a priority following spinal cord injury, with the
      majority of people remaining sexually active with a satisfying sex life.
      Nevertheless, rehabilitation programmes often focus on activities related to
      mobility and elimination, with sexual health relegated to a secondary under
      resourced position. DESIGN: Model creation and audit of current and desired
      status to identify required education. METHODS: A four-tier model for sexual
      health management identified phases of management, increasing in complexity, from
      tier 1 to tier 4. The model was used to audit the current and desired status of
      the multidisciplinary team on a spinal injuries unit, identifying knowledge
      levels, barriers to involvement and education requirements. RESULTS: Fifty-nine
      questionnaires were completed (85%) by nurses and allied health professionals.
      Knowledge deficits and discomfort with the topic were the primary reasons
      prohibiting involvement with sexual health rehabilitation. Two thirds were
      willing to be involved with sexual health activities, mainly at an introductory
      level rather than providing education or problem-solving. However, following
      relevant education, the level of involvement changed: 90% (n = 53) desired
      involvement at more complex levels, and 10% (n = 6) were unwilling to be
      involved. CONCLUSIONS: Developing the necessary skills and knowledge creates
      potential to increase the resources available to participate in sexual health
      rehabilitation following a spinal cord injury and ensure that it is a core
      rehabilitation activity. RELEVANCE TO CLINICAL PRACTICE: The progressive model
      portrayed discrete phases of sexual health management, which collectively portray
      the whole. Team members identified a level of involvement to compliment their
      skills and knowledge. The audit demonstrated that the primary barriers to
      involvement were not culture, language or attitude as hypothesised, but
      inadequate knowledge, addressable through education.

PMID- 24580793
TI  - The illness experience of middle-aged men with oral cancer.
AB  - AIMS AND OBJECTIVES: To explore the essence of the illness experiences of middle
      aged men with oral cancer. BACKGROUND: Having oral cancer creates great
      challenges in the lives of middle-aged men and their families. Understanding
      patients' experiences provides a sound basis for patient-centred and
      individualised care. Research is limited regarding the illness experience of
      middle-aged men with oral cancer with regard to facing both the invasion of
      disease and the responsibilities of middle age. DESIGN: A phenomenology approach
      was used. METHODS: Nine men diagnosed with oral cancer within one year were
      recruited during 2009 and 2010. Data were collected through individual in-depth
      interviews and analysed using Colaizzi's phenomenological analysis procedures.
      RESULTS: The following five themes emerged from the patterns of categorised
      interview data: the psychological journey in facing oral cancer, the question of
      how patients can control their disease as well as the sequelae of cancer
      treatment, the continuous disturbance and turmoil resulting from the disease, the
      appreciation of the support from family and friends, and the ability to learn to
      actively face the future. CONCLUSIONS: Patients with oral cancer experienced
      tremendous physical, psychosocial and financial challenges. Although burdened
      with multiple stressors, these middle-aged men were able to learn from their
      experiences and exhibit positive growth in life. RELEVANCE TO CLINICAL PRACTICE:
      Patients with oral cancer have to constantly adjust to the impact of their
      disease. The study results may serve as a reference for improving clinical
      practice and the quality of care among patients with oral cancer. Cancer care is
      multidimensional and holistic. Healthcare professionals should develop a set of
      plans by which patients receive complete medical care and support, as well as
      assistance from professionals and family members, as their treatment progresses
      to help patients face the challenges of cancer.

PMID- 24580794
TI  - Let's talk about sex: lower limb amputation, sexual functioning and sexual well
      being: a qualitative study of the partner's perspective.
AB  - AIMS AND OBJECTIVES: To describe the impact of patients' lower limb amputations
      on their partners' sexual functioning and well-being. BACKGROUND: Annually, about
      3300 major lower limb amputations are performed in the Netherlands. An amputation
      may induce limitations in performing marital activities, including expression of
      sexual feelings between partners. However, up until now, little attention has
      been paid towards this aspect in both research and clinical practice. The lack of
      studies on sexual activities and lower limb amputation is even more apparent with
      respect to partners of patients with such an amputation. Previous studies have
      shown, however, that the presence of a disease or disability may have a large
      impact not only on the patient's but also on the partner's sexual activities.
      DESIGN: Qualitative thematic analysis. METHODS: Semi-structured interviews. The
      questions used in the interview were inspired by a generic framework about
      chronic disease and sexual functioning and well-being. In total, 16 partners of
      patients with a lower limb amputation who were at least 18 years old were
      recruited in different rehabilitation centres. RESULTS: Seven major themes (i.e.
      importance of sexuality, thoughts about sexuality before the amputation, changes
      in sexual functioning and sexual well-being, amputation as the main cause of
      these changes, acceptance of the amputation, role confusion and communication
      about sexuality) were derived from the interviews. Minor changes in sexual
      functioning and sexual well-being were reported by the participants. Problems
      participants did encounter were solved by the couples themselves. For some
      participants, their sexual well-being improved after the amputation. CONCLUSION
      AND RELEVANCE TO CLINICAL PRACTICE: Participants in our study reported minor
      changes in their sexual well-being. Most of them indicated that communication
      about the changes expected and how to cope with these would have been helpful. It
      is therefore important that professionals address sexuality during the
      rehabilitation process with patients and partners.

PMID- 24580795
TI  - How does the mining industry contribute to sexual and reproductive health in
      developing countries? A narrative synthesis of current evidence to inform
      practice.
AB  - AIMS AND OBJECTIVES: To explore client and provider experiences and related
      health outcomes of sexual and reproductive health interventions that have been
      led by or that have involved mining companies. BACKGROUND: Miners, and those
      living in communities surrounding mines in developing countries, are a vulnerable
      population with a high sexual and reproductive health burden. People in these
      communities require specific healthcare services although the exact delivery
      needs are unclear. There are no systematic reviews of evidence to guide delivery
      of sexual and reproductive health interventions to best address the needs of men
      and women in mining communities. DESIGN: A narrative synthesis. METHODS: A search
      of peer-reviewed literature from 2000-2012 was undertaken with retrieved
      documents assessed using an inclusion/exclusion criterion and quality appraisal
      guided by critical assessment tools. Concepts were analysed thematically.
      RESULTS: A desire for HIV testing and treatment was associated with the
      recognition of personal vulnerability, but this was affected by fear of stigma.
      Regular on-site services facilitated access to voluntary counselling and testing
      and HIV care, but concerns for confidentiality were a serious barrier. The
      provision of HIV and sexually transmitted infection clinical and promotive
      services revealed mixed health outcomes. Recommended service improvements
      included rapid HIV testing, the integration of sexual and reproductive health
      into regular health services also available to family members and culturally
      competent, ethical, providers who are better supported to involve consumers in
      health promotion. CONCLUSION: There is a need for research to better inform
      health interventions so that they build on local cultural norms and values and
      address social needs. A holistic approach to sexual and reproductive health
      beyond a focus on HIV may better engage community members, mining companies and
      governments in healthcare delivery. RELEVANCE TO CLINICAL PRACTICE: Nurses may
      require appropriate workplace support and incentives to deliver sexual and
      reproductive health interventions in developing mining contexts where task
      shifting exists.

PMID- 24580796
TI  - Muted, but not mute.

PMID- 24580797
TI  - Plumes of neuronal activity propagate in three dimensions through the nuclear
      avian brain.
AB  - BACKGROUND: In mammals, the slow-oscillations of neuronal membrane potentials
      (reflected in the electroencephalogram as high-amplitude, slow-waves), which
      occur during non-rapid eye movement sleep and anesthesia, propagate across the
      neocortex largely as two-dimensional traveling waves. However, it remains unknown
      if the traveling nature of slow-waves is unique to the laminar cytoarchitecture
      and associated computational properties of the neocortex. RESULTS: We demonstrate
      that local field potential slow-waves and correlated multiunit activity propagate
      as complex three-dimensional plumes of neuronal activity through the avian brain,
      owing to its non-laminar, nuclear neuronal cytoarchitecture. CONCLUSIONS: The
      traveling nature of slow-waves is not dependent upon the laminar organization of
      the neocortex, and is unlikely to subserve functions unique to this pattern of
      neuronal organization. Finally, the three-dimensional geometry of propagating
      plumes may reflect computational properties not found in mammals that contributed
      to the evolution of nuclear neuronal organization and complex cognition in birds.

PMID- 24580798
TI  - Thyroid disease in insulin-treated patients with type 2 diabetes: a retrospective
      study.
AB  - BACKGROUND: Diabetes mellitus and thyroid diseases frequently coexist. In order
      to evaluate how thyroid disorders interfere with glycemic control, we analysed
      insulin-treated type 2 diabetes patients with thyroid disease. METHODS: Diabetes
      patients (n = 1.957) were retrospectively investigated. We focused on type 2
      diabetes patients who had been admitted for insulin-treatment and diagnosed
      thyroid diseases (n = 328). Patients were divided into three groups according to
      thyroid disease manifestation in relation to diabetes onset: prior to (group 1),
      same year (group 2) and thyroid disease following diabetes (group 3). RESULTS:
      Out of all diabetes patients 27.3% had a thyroid disorder with more women (62.2%)
      being affected (p < 0.001). Thyroid disease was predominantly diagnosed after
      diabetes onset. Patients with type 2 diabetes and prior appearance of thyroid
      disease required insulin therapy significantly earlier (median insulin-free
      period: 2.5 yrs; Q1 = 0.0, Q3 = 8.25) compared to patients who had thyroid
      dysfunction after diabetes onset (median insulin-free period: 8.0 yrs; Q1 = 3.0,
      Q3 = 12.0; p < 0.001). Age at diabetes onset correlated with insulin-free period
      (p < 0.001). CONCLUSIONS: Thyroid disease may be a marker of a distinct metabolic
      trait in type 2 diabetes potentially requiring earlier insulin treatment.

PMID- 24580800
TI  - The European Union Committee of Experts on Rare Diseases: three productive years
      at the service of the rare disease community.
AB  - The European Union Committee of Experts on Rare Diseases was entrusted with
      aiding the European Commission in a number of tasks, ranging from the monitoring
      of initiatives, to recommending improvements and actions to be pursued in the
      future, in addition to helping strengthen liaison at both European and
      International levels in the field of rare diseases. The three-year mandate of the
      EUCERD drew to a close in July 2013 with an impressive record. The EUCERD has
      laid down the foundations for future work so as to continue to advance in the key
      areas that have been identified as of interest for the rare disease community at
      large: centres of expertise, European Reference Networks, patient registries and
      databases, newborn screening, and indicators for national rare disease
      plans/strategies. The work of the Committee should now be continued by the newly
      formed European Commission Expert Group on Rare Diseases. 

PMID- 24580799
TI  - Physical activity and the risk of postmenopausal breast cancer - the Norwegian
      Women and Cancer Study.
AB  - BACKGROUND: The relationship between physical activity (PA) throughout life and
      the risk of postmenopausal breast cancer overall and by estrogen receptor (ER)
      and progesterone receptor (PR) status, has been reported, but without consistent
      results. The present study aimed to investigate PA from young age to adulthood in
      participants of the Norwegian Women and Cancer (NOWAC) Study, in order to
      determine whether changes in PA level affect the risk of postmenopausal breast
      cancer. METHODS: 1767 invasive breast cancer cases were identified among 80,202
      postmenopausal participants of the NOWAC Study during 8.2 years of median follow
      up. PA levels at age 14 years, 30 years and at cohort enrollment were obtained
      via a self-administered questionnaire. Multivariate Cox proportional hazard
      regression models were used to estimate relative risks and 95% confidence
      intervals of the risk of postmenopausal breast cancer overall and by ER/PR
      status. RESULTS: Risk of postmenopausal breast cancer overall and by ER/PR status
      was not associated with physical activity level at enrollment. Women with a low
      PA level at age 30 had an increased risk of ER+/PR + breast tumors (P for trend =
      0.04) compared to women with a moderate physical activity level at age 30. Women
      with a low physical activity level at all three periods of life had a 20%
      significantly reduced risk of postmenopausal breast cancer, as well as a reduced
      risk of ER+/PR + and ER+/PR- breast tumors, compared with women who maintained a
      moderate physical activity level. However, when analyses were corrected for
      multiple tests, the result was no longer statistically significant. The findings
      were consistent over strata of age, body mass index and use of hormone
      replacement therapy. CONCLUSIONS: The study results from this large Norwegian
      cohort do not support an association between physical activity at different
      periods of life and the risk of postmenopausal breast cancer.

PMID- 24580801
TI  - Efficacy and safety of once-daily maraviroc plus ritonavir-boosted darunavir in
      pretreated HIV-infected patients in a real-life setting.
AB  - OBJECTIVES: Nucleoside reverse transcriptase inhibitor (NRTI)-sparing regimens
      may be needed in patients with NRTI toxicity. Maraviroc (MVC) plus ritonavir
      boosted darunavir (DRV-r) or atazanavir is associated with slightly lower
      response rates than triple therapy in drug-naive patients. No information is
      available on these combinations in pretreated patients. The aim of this study was
      to assess the efficacy and safety of MVC plus DRV/r once-daily (qd) in HIV
      infected pretreated patients. METHODS: A retrospective cohort study including
      patients starting MVC 150 mg plus DRV/r 800/100 mg qd, with CCR5 tropism and no
      resistance mutations for DRV/r, was performed. The primary efficacy endpoint was
      the achievement of plasma HIV RNA < 50 HIV-1 RNA copies/mL after 48 weeks. The
      frequency of serious adverse effects was investigated. RESULTS: Sixty patients
      were recruited to the study, of whom 48 (80%) had HIV RNA < 50 copies/mL at
      baseline. Reasons for starting MVC plus DRV/r were: adverse effects in 38
      individuals (63%), simplification in 15 (25%) and virological failure in seven
      (12%). The main analysis (intention to treat, noncompleter = failure) showed that
      47 patients (78%) achieved HIV RNA < 50 copies/mL at 48 weeks (paired comparison
      with baseline, P = 1.0). On-treatment analysis showed that 42 (86%) of 49
      patients presented HIV RNA < 50 copies/mL at 48 weeks (paired comparison with
      baseline, P = 1.0). Median (interquartile range) CD4 cell counts increased from
      491 (301-729) to 561 (367-793) cells/MUL at 48 weeks (P = 0.013). Only one
      patient discontinued therapy because of adverse effects. CONCLUSIONS: Most
      individuals starting MVC plus DRV/r qd because of simplification or adverse
      effects maintained HIV suppression after 48 weeks of follow-up.

PMID- 24580802
TI  - I Move: systematic development of a web-based computer tailored physical activity
      intervention, based on motivational interviewing and self-determination theory.
AB  - BACKGROUND: This article describes the systematic development of the I Move
      intervention: a web-based computer tailored physical activity promotion
      intervention, aimed at increasing and maintaining physical activity among adults.
      This intervention is based on the theoretical insights and practical applications
      of self-determination theory and motivational interviewing. METHODS/DESIGN: Since
      developing interventions in a systemically planned way increases the likelihood
      of effectiveness, we used the Intervention Mapping protocol to develop the I Move
      intervention. In this article, we first describe how we proceeded through each of
      the six steps of the Intervention Mapping protocol. After that, we describe the
      content of the I Move intervention and elaborate on the planned randomized
      controlled trial. DISCUSSION: By integrating self-determination theory and
      motivational interviewing in web-based computer tailoring, the I Move
      intervention introduces a more participant-centered approach than traditional
      tailored interventions. Adopting this approach might enhance computer tailored
      physical activity interventions both in terms of intervention effectiveness and
      user appreciation. We will evaluate this in an randomized controlled trial, by
      comparing the I Move intervention to a more traditional web-based computer
      tailored intervention. TRIAL REGISTRATION: NTR4129.

PMID- 24580804
TI  - Dai Huang Fu Zi Tang could ameliorate intestinal injury in a rat model of
      hemorrhagic shock by regulating intestinal blood flow and intestinal expression
      of p-VASP and ZO-1.
AB  - BACKGROUND: Dai Huang Fu Zi Tang (DHFZT), an oriental herbal formula, has long
      been used clinically in treatment of intestinal obstruction, acute pancreatitis,
      cholecystalgia and chronic diarrhea for thousands of years. Recent studies have
      demonstrated that DHFZT can reduce intestinal pathological injury and the
      concentration of enterogenous endotoxin in an animal model. But the underlying
      mechanism has not been fully elucidated. METHODS: SD male rats in adult were used
      to model HS and treated with DHFZT. The serum concentration of endotoxin were
      analyzed by dynamic turbidimetric method. In addition, the blood flow of small
      intestine were measured using laser speckle technique. Phosphorylated vasodilator
      stimulated phosphoprotein (p-VASP) and zonula occludens (ZO)-1 protein,
      intestinal fatty acid binding protein (IFABP) were measured by Western Blotting,
      RT-PCR, ELISA respectively. RESULTS: Present study showed that DHFZT markedly
      elevated the blood flow of small intestine, protected the intestinal barrier
      function by up-regulating the expression of ZO-1 protein and down-regulating
      expression of p-VASP, and notely decreased serum concentration of IFABP and
      endotoxin in HS. CONCLUSIONS: These results reveal that DHFZT improves intestinal
      blood flow, protects the intestinal barrier function, and ameliorates intestinal
      endotoxaemia in rats with HS.

PMID- 24580805
TI  - Craniofacial divergence by distinct prenatal growth patterns in Fgfr2 mutant
      mice.
AB  - BACKGROUND: Differences in cranial morphology arise due to changes in fundamental
      cell processes like migration, proliferation, differentiation and cell death
      driven by genetic programs. Signaling between fibroblast growth factors (FGFs)
      and their receptors (FGFRs) affect these processes during head development and
      mutations in FGFRs result in congenital diseases including FGFR-related
      craniosynostosis syndromes. Current research in model organisms focuses primarily
      on how these mutations change cell function local to sutures under the hypothesis
      that prematurely closing cranial sutures contribute to skull dysmorphogenesis.
      Though these studies have provided fundamentally important information
      contributing to the understanding of craniosynostosis conditions, knowledge of
      changes in cell function local to the sutures leave change in overall three
      dimensional cranial morphology largely unexplained. Here we investigate growth of
      the skull in two inbred mouse models each carrying one of two gain-of-function
      mutations in FGFR2 on neighboring amino acids (S252W and P253R) that in humans
      cause Apert syndrome, one of the most severe FGFR-related craniosynostosis
      syndromes. We examine late embryonic skull development and suture patency in
      Fgfr2 Apert syndrome mice between embryonic day 17.5 and birth and quantify the
      effects of these mutations on 3D skull morphology, suture patency and growth.
      RESULTS: We show in mice what studies in humans can only infer: specific cranial
      growth deviations occur prenatally and worsen with time in organisms carrying
      these FGFR2 mutations. We demonstrate that: 1) distinct skull morphologies of
      each mutation group are established by E17.5; 2) cranial suture patency patterns
      differ between mice carrying these mutations and their unaffected littermates; 3)
      the prenatal skull grows differently in each mutation group; and 4) unique Fgfr2
      related cranial morphologies are exacerbated by late embryonic growth patterns.
      CONCLUSIONS: Our analysis of mutation-driven changes in cranial growth provides a
      previously missing piece of knowledge necessary for explaining variation in
      emergent cranial morphologies and may ultimately be helpful in managing human
      cases carrying these same mutations. This information is critical to the
      understanding of craniofacial development, disease and evolution and may
      contribute to the evaluation of incipient therapeutic strategies.

PMID- 24580806
TI  - Screening for post-traumatic stress disorder after injury in the pediatric
      emergency department--a systematic review protocol.
AB  - BACKGROUND: Pediatric injury is highly prevalent and has significant impact both
      physically and emotionally. The majority of pediatric injuries are treated in
      emergency departments (EDs), where treatment of physical injuries is the main
      focus. In addition to physical trauma, children often experience significant
      psychological trauma, and the development of acute stress disorder (ASD) and post
      traumatic stress disorder (PTSD) is common. The consequences of failing to
      recognize and treat children with ASD and PTSD are significant and extend into
      adulthood. Currently, screening guidelines to identify children at risk for
      developing these stress disorders are not evident in the pediatric emergency
      setting. The goal of this systematic review is to summarize evidence on the
      psychometric properties, diagnostic accuracy, and clinical utility of screening
      tools that identify or predict PTSD secondary to physical injury in children.
      Specific research objectives are to: (1) identify, describe, and critically
      evaluate instruments available to screen for PTSD in children; (2) review and
      synthesize the test-performance characteristics of these tools; and (3) describe
      the clinical utility of these tools with focus on ED suitability. METHODS:
      Computerized databases including MEDLINE, EMBASE, CINAHL, ISI Web of Science and
      PsycINFO will be searched in addition to conference proceedings, textbooks, and
      contact with experts. Search terms will include MeSH headings (post-traumatic
      stress or acute stress), (pediatric or children) and diagnosis. All articles will
      be screened by title/abstract and articles identified as potentially relevant
      will be retrieved in full text and assessed by two independent reviewers. Quality
      assessment will be determined using the QUADAS-2 tool. Screening tool
      characteristics, including type of instrument, number of items, administration
      time and training administrators level, will be extracted as well as gold
      standard diagnostic reference properties and any quantitative diagnostic data
      (specificity, positive and negative likelihood/odds ratios) where appropriate.
      DISCUSSION: Identifying screening tools to recognize children at risk of
      developing stress disorders following trauma is essential in guiding early
      treatment and minimizing long-term sequelae of childhood stress disorders. This
      review aims to identify such screening tools in efforts to improve routine stress
      disorder screening in the pediatric ED setting. TRIALS REGISTRATION: PROSPERO
      registration: CRD42013004893.

PMID- 24580807
TI  - Kraken: ultrafast metagenomic sequence classification using exact alignments.
AB  - Kraken is an ultrafast and highly accurate program for assigning taxonomic labels
      to metagenomic DNA sequences. Previous programs designed for this task have been
      relatively slow and computationally expensive, forcing researchers to use faster
      abundance estimation programs, which only classify small subsets of metagenomic
      data. Using exact alignment of k-mers, Kraken achieves classification accuracy
      comparable to the fastest BLAST program. In its fastest mode, Kraken classifies
      100 base pair reads at a rate of over 4.1 million reads per minute, 909 times
      faster than Megablast and 11 times faster than the abundance estimation program
      MetaPhlAn. Kraken is available at http://ccb.jhu.edu/software/kraken/. 

PMID- 24580809
TI  - A past with uncertainty, a future with hope--rare disease day 2014 from a USA
      perspective.
AB  - We reflect on the worldwide research accomplishments, orphan product approvals,
      and the commitments by the rare diseases community. Major collaborative efforts
      by the public and private sectors increased interventions and diagnostics for
      rare diseases. We marvel at the impact of safe and effective treatments when they
      become available. Hope remains for the rare diseases community with a renewed
      commitment and acceptance of collaborative public-private partnerships of
      government translational research and regulatory programs, the biopharmaceutical,
      devices and diagnostics industries, academic investigators, and patient advocacy
      groups. The global rare diseases community remains strong and responsive to the
      voices and needs of patients, families, and clinicians awaiting diagnosis and
      treatment for their disease. We anticipate even greater successes in 2014 to
      reflect on Rare Disease Day 2015. 

PMID- 24580808
TI  - Therapy duration and long-term outcomes in extra-pulmonary tuberculosis.
AB  - BACKGROUND: Tuberculosis is classified as either pulmonary or extra-pulmonary
      (EPTB). While much focus has been paid to pulmonary tuberculosis, EPTB has
      received scant attention. Moreover, EPTB is viewed as one wastebasket diagnosis,
      as "the other" which is not pulmonary. METHODS: This is a retrospective cohort
      study of all patients treated for EPTB in the state of Texas between January 2000
      and December 2005, who had no pulmonary disease. Clinical and epidemiological
      factors were abstracted from electronic records of the Report of Verified Case of
      Tuberculosis. The long-term outcome, which is death by December 2011, was
      established using the Social Security Administration Death Master File database.
      Survival in EPTB patients was compared to those with latent tuberculosis, as well
      as between different types of EPTB, using Cox proportional hazard models. A
      hybrid of the machine learning method of classification and regression tree
      analyses and standard regression models was used to identify high-order
      interactions and clinical factors predictive of long-term all-cause mortality.
      RESULTS: Four hundred and thirty eight patients met study criteria; the median
      study follow-up period for the cohort was 7.8 (inter-quartile range 6.0-10.1)
      years. The overall all-cause mortality rate was 0.025 (95% confidence interval
      [CI]: 0.021-0.030) per 100 person-year of follow-up. The significant predictors
      of poor long-term outcome were age (hazard ratio [HR] for each year of age-at
      diagnosis was 1.05 [CI: 1.04-1.06], treatment duration, type of EPTB and HIV
      infection (HR = 2.16; CI: 1.22, 3.83). Mortality in genitourinary tuberculosis
      was no different from latent tuberculosis, while meningitis had the poorest long
      term outcome of 46.2%. Compared to meningitis the HR for death was 0.50 (CI: 0.27
      0.91) for lymphatic disease, 0.42 (CI: 0.21-0.81) for bone/joint disease, and
      0.59 (CI: 0.27-1.31) for peritonitis. The relationship between mortality and
      therapy duration for each type of EPTB was a unique "V" shaped curve, with the
      lowest mortality observed at different therapy durations for each, beyond which
      mortality increased. CONCLUSIONS: EPTB is comprised of several different diseases
      with different outcomes and durations of therapy. The "V" shaped relationship
      between therapy duration and outcome leads to the hypothesis that longer duration
      of therapy may lead to higher patient mortality.

PMID- 24580810
TI  - On the relationship between gingival biotypes and gingival thickness in young
      Caucasians.
AB  - OBJECTIVES: To evaluate a possible relationship between gingival biotypes and
      gingival thickness, papilla height and gingival width. MATERIAL AND METHODS:
      Thirty-six adult subjects were stratified by their gingival biotype (GB), as
      defined by transparency of a periodontal probe through the buccal gingival
      margin, into "thin" (18 subjects) and "thick" (18 subjects) GB. Out of these,
      extreme cases (6 "very thin", 6 "very thick") were identified. Four different
      parameters were assessed: gingival thickness (GT), papilla height (PH), probing
      depth (PD) and gingival width (GW). RESULTS: When comparing "thin" and "thick"
      GB, midfacial GT (0.40 +/- 0.07 vs. 0.72 +/- 0.11 mm; P < 0.0001), PH (3.76 +/-
      0.50 vs. 3.95 +/- 0.41 mm, P = 0.02) and GW (3.01 +/- 1.26 vs. 4.63 +/- 0.86 mm,
      P = 0.04) were lower in the "thin" GB group. Further stratification into
      moderately and extremely "thin"/"thick" GB eliminated the differences between the
      moderate groups. CONCLUSION: Our data support the traditional hypothesis that two
      different gingival biotypes with concomitant properties distinguishable by
      gingival transparency exist. In addition, we provide evidence that an alternative
      classification into "very thick", "moderate" and "very thin" biotypes might be
      advantageous, because the unique properties were seemingly primarily driven by
      subjects with extreme values.

PMID- 24580812
TI  - GABAergic neurons in the ventral tegmental area receive dual GABA/enkephalin
      mediated inhibitory inputs from the bed nucleus of the stria terminalis.
AB  - Activation of mu-opioid receptor (MOR) disinhibits dopaminergic neurons in the
      ventral tegmental area (VTA) through inhibition of gamma-aminobutyric acid
      (GABA)ergic neurons. This mechanism is thought to play a pivotal role in
      mediating reward behaviors. Here, we characterised VTA-projecting enkephalinergic
      neurons in the anterior division of the bed nucleus of the stria terminalis (BST)
      and investigated their targets by examining MOR expression in the VTA. In the
      BST, neurons expressing preproenkephalin mRNA were exclusively GABAergic, and
      constituted 37.2% of the total GABAergic neurons. Using retrograde tracer
      injected into the VTA, 21.6% of VTA-projecting BST neurons were shown to express
      preproenkephalin mRNA. Enkephalinergic projections from the BST exclusively
      formed symmetrical synapses onto the dendrites of VTA neurons. In the VTA, 74.1%
      of MOR mRNA-expressing neurons were GABAergic, with the rest being glutamatergic
      neurons expressing type-2 vesicular glutamate transporter mRNA. However, MOR mRNA
      was below the detection threshold in dopaminergic neurons. By
      immunohistochemistry, MOR was highly expressed on the extrasynaptic membranes of
      dendrites in GABAergic VTA neurons, including dendrites innervated by BST-VTA
      projection terminals. MOR was also expressed weakly on GABAergic and
      glutamatergic terminals in the VTA. Given that GABAA alpha1 is expressed at
      GABAergic BST-VTA synapses on dendrites of GABAergic neurons [T. Kudo et al.
      (2012) J. Neurosci., 32, 18035-18046], our results collectively indicate that the
      BST sends dual inhibitory outputs targeting GABAergic VTA neurons; GABAergic
      inhibition via 'wired' transmission, and enkephalinergic inhibition via 'volume'
      transmission. This dual inhibitory system provides the neural substrate
      underlying the potent disinhibitory control over dopaminergic VTA neurons exerted
      by the BST. 

PMID- 24580811
TI  - Proteogenomics of selective susceptibility to endotoxin using circulating acute
      phase biomarkers and bioassay development in sheep: a review.
AB  - Scientists have injected endotoxin into animals to investigate and understand
      various pathologies and novel therapies for several decades. Recent observations
      have shown that there is selective susceptibility to Escherichia coli
      lipopolysaccharide (LPS) endotoxin in sheep, despite having similar breed
      characteristics. The reason behind this difference is unknown, and has prompted
      studies aiming to explain the variation by proteogenomic characterisation of
      circulating acute phase biomarkers. It is hypothesised that genetic trait,
      biochemical, immunological and inflammation marker patterns contribute in
      defining and predicting mammalian response to LPS. This review discusses the
      effects of endotoxin and host responses, genetic basis of innate defences,
      activation of the acute phase response (APR) following experimental LPS
      challenge, and the current approaches employed in detecting novel biomarkers
      including acute phase proteins (APP) and micro-ribonucleic acids (miRNAs) in
      serum or plasma. miRNAs are novel targets for elucidating molecular mechanisms of
      disease because of their differential expression during pathological, and in
      healthy states. Changes in miRNA profiles during a disease challenge may be
      reflected in plasma. Studies show that gel-based two-dimensional electrophoresis
      (2-DE) coupled with either matrix-assisted laser desorption/ionisation time-of
      flight mass spectrometry (MALDI-TOF MS) or liquid chromatography-mass
      spectrometry (LC-MS/MS) are currently the most used methods for proteome
      characterisation. Further evidence suggests that proteomic investigations are
      preferentially shifting from 2-DE to non-gel based LC-MS/MS coupled with data
      extraction by sequential window acquisition of all theoretical fragment-ion
      spectra (SWATH) approaches that are able to identify a wider range of proteins.
      Enzyme-linked immunosorbent assay (ELISA), quantitative real-time polymerase
      chain reaction (qRT-PCR), and most recently proteomic methods have been used to
      quantify low abundance proteins such as cytokines. qRT-PCR and next generation
      sequencing (NGS) are used for the characterisation of miRNA. Proteogenomic
      approaches for detecting APP and novel miRNA profiling are essential in
      understanding the selective resistance to endotoxin in sheep. The results of
      these methods could help in understanding similar pathology in humans. It might
      also be helpful in the development of physiological and diagnostic screening
      assays for determining experimental inclusion and endpoints, and in clinical
      trials in future. 

PMID- 24580814
TI  - Mitigation of Cu stress by legume-Rhizobium symbiosis in white lupin and soybean
      plants.
AB  - The effect of Bradyrhizobium-legume symbiosis on plant growth, toxicological
      variables and Cu bioaccumulation was studied in white lupin and soybean plants
      treated with 1.6, 48, 96 and 192 MUM Cu. In both species, those plants grown in
      the presence of root nodule-forming symbiotic Bradyrhizobium showed less root and
      shoot growth reduction, plus greater translocation of Cu to the shoot, than those
      grown without symbiotic Bradyrhizobium. The effective added concentrations of Cu
      that reduced shoot and root dry weight by 50% (EC50), and the critical toxic
      concentration that caused a 10% reduction in plant growth (CTC10%), were higher
      in plants grown with symbiotic Bradyrhizobium, and were in general higher in the
      roots whether the plants were grown with or without these bacteria. The
      production of malondialdehyde and total thiols was stimulated by Cu excess in the
      shoots and roots of white lupin grown with or without symbiotic Bradyrhizobium,
      but mainly in those without the symbionts. In contrast, in soybean, the increases
      in malondialdehyde and total thiols associated with rising Cu concentration were
      a little higher (1.2-5.0 and 1.0-1.6 times respectively) in plants grown with
      symbiotic Bradyrhizobium than without. Finally, the organ most sensitive to Cu
      excess was generally the shoot, both in white lupin and soybean grown with or
      without symbiotic Bradyrhizobium. Further, Bradyrhizobium-legume symbiosis
      appears to increase the tolerance to Cu excess in both legumes, but mainly in
      white lupin; plant growth was less reduced and CTC10% and EC50 values increased
      compared to plants grown without symbiotic Bradyrhizobium. Bradyrhizobium N2
      fixation in both legumes would therefore seem to increase the phytoremediation
      potential of these plants when growing on Cu-contaminated sites.

PMID- 24580813
TI  - Helping our patients take HIV pre-exposure prophylaxis (PrEP): a systematic
      review of adherence interventions.
AB  - OBJECTIVES: Adherence is critical for maximizing the effectiveness of pre
      exposure prophylaxis (PrEP) in preventing HIV infection. Strategies for promoting
      adherence to HIV treatment, and their potential application to PrEP adherence,
      have received considerable attention. However, adherence promotion strategies for
      prevention medications have not been well characterized and may be more
      applicable to PrEP. We aimed to identify adherence support interventions that
      have been effective in other prevention fields and could be applied in the HIV
      prevention context to support pill taking among PrEP users. METHODS: To identify
      adherence support interventions that could be evaluated and applied in the PrEP
      context, we conducted a systematic review across the following prevention fields:
      hypertension, latent tuberculosis infection, hyperlipidaemia, oral
      contraceptives, osteoporosis, malaria prophylaxis, and post-exposure prophylaxis
      for HIV infection. We included randomized controlled trials that evaluated the
      efficacy of interventions to improve adherence to daily oral medications
      prescribed for primary prevention in healthy individuals or for secondary
      prevention in asymptomatic individuals. RESULTS: Our searches identified 585
      studies, of which 48 studies met the eligibility criteria and were included in
      the review; nine evaluated multiple strategies, yielding 64 separately tested
      interventions. Interventions with the strongest evidence for improving adherence
      included complex, resource-intensive interventions, which combined multiple
      adherence support approaches, and low-cost, low-intensity interventions that
      provided education or telephone calls for adherence support. CONCLUSIONS: Our
      review identified adherence interventions with strong evidence of efficacy across
      prevention fields and provides recommendations for evaluating these interventions
      in upcoming PrEP studies.

PMID- 24580815
TI  - Kinetic response of a genotoxicity biomarker in the three-spined stickleback and
      implication for environmental monitoring.
AB  - The ultimate sink for the majority of anthropogenic compounds are the aquatic
      ecosystems, either through direct discharges or indirectly through hydrologic or
      atmospheric processes, possibly leading to long-term adverse effects in aquatic
      living resources. In order to assess exposure, fate and effects of chemical
      contaminants, aquatic ecotoxicologists have developed a large array of early
      warning biomarkers proving that toxicants have entered organisms, have been
      distributed between organs and have triggered toxic effects regarding critical
      targets. However, optimal use of biomarkers in environmental studies previously
      requires in-depth knowledge of the kinetics of response of biomarkers. This work
      aimed to define as a first step of a validation process the kinetic response of a
      genotoxicity biomarker recently developed in the three-spined stickleback
      (Gasterosteus aculeatus). DNA damage was assessed in stickleback erythrocytes
      after in vivo exposure for 12 days to methylmethanesulfonate (MMS), an alkylating
      compound, followed by a 20 day-recovery period. Results show a dose-response
      relationship, time to maximal induction being reached after 6 days at the highest
      MMS concentration. No acclimation process was noticed during exposure whatever
      the MMS concentration, and genotoxicity decreased during the recovery phase only
      in fish exposed to the highest MMS concentration, suggesting more an effect of
      erythrocyte turn-over than of DNA repair system on the observed DNA damage level.
      Further field experiments are needed before including this genotoxicity biomarker
      in a battery of biochemical markers to monitor adverse effects of pollutants on
      fish health. 

PMID- 24580816
TI  - A multi-biomarker assessment of single and combined effects of norfloxacin and
      sulfamethoxazole on male goldfish (Carassius auratus).
AB  - In the present study, the sublethal effects of norfloxacin alone and in
      combination with sulfamethoxazole in goldfish (Carassius auratus) were
      investigated, the biomarkers including acetylcholinesterase (AChE) in brain, 7
      ethoxyresorufin O-deethylase (EROD), glutathione S-transferase (GST), and
      superoxides dismutase (SOD) activities in liver, vitellogenin (Vtg) in serum and
      DNA damage in gonad were determined after 1, 2, 4 and 7 days of exposure. Brain
      AChE activity was significantly inhibited by norfloxacin (>=0.4 mg/L) after 4 and
      7 days and the mixtures with sulfamethoxazole (>=0.24 mg/L) after 4 days of
      exposure, and significant concentration-response relationships were obtained.
      Liver EROD, GST and SOD activities were significantly increased by the individual
      and mixed pharmaceuticals in most cases and exhibited analogously bell-shaped
      concentration-response curves. Serum Vtg was increased by the highest
      concentration of norfloxacin and two higher concentrations of the mixtures.
      Higher concentrations of the test antibiotics induced significant DNA damage in a
      concentration- and time-dependent manner. The results indicated that selected
      antibiotics possesses cytotoxic and genotoxic potential against the non-target
      organism C. auratus.

PMID- 24580817
TI  - Sequential extraction of anaerobic digestate sludge for the determination of
      partitioning of heavy metals.
AB  - In China, agricultural use of anaerobic digestate sludge is considered a concern
      due to high heavy metal content of the sludge. In this study, sequential
      extraction procedure (SEP) was conducted to determine metal speciation which
      affects release and mobility of metal significantly. The results of SEP showed
      that each heavy metal possessed different distribution characteristics. Cu mainly
      reacted with carboxyl functional group to form the fraction bound to organic
      matter. Zn and Mn were dominated in the fraction bound to Fe-Mn oxides and
      carbonates, respectively. Pb, Ni, Cr, Cd and As were present as the residual
      fraction. Examination of mobility factors (MFs) indicated that Zn, Pb, Ni, Mn and
      Cd were more mobile whereas Cr and As were immobilized in anaerobic digestate.
      Based on the results, it can be stated that Cu, Zn, Mn, Ni and Cd may be grouped
      as toxic and active components in sludge and should be regarded as the priority
      pollutants for elimination. Pb should be monitored in terms of its high mobility
      factors (MF). Cr and As, nevertheless, were the most stable components in sludge.

PMID- 24580818
TI  - Hydrogen sulfide alleviates lead-induced photosynthetic and ultrastructural
      changes in oilseed rape.
AB  - The role of hydrogen sulfide (H2S) in alleviating lead (Pb) induced stress in
      oilseed rape (Brassica napus L.) was studied under laboratory conditions. Plants
      were grown hydroponically in greenhouse conditions under three levels (0, 100,
      and 400 uM) of Pb and three levels (0, 100 and 200 uM) of H2S donor, sodium
      hydrosulfide (NaHS). Application of H2S significantly improved the plant growth,
      root morphology, chlorophyll contents and photosynthetic activity in leaves of B.
      napus under Pb stress. Moreover, exogenously applied H2S significantly lowered
      the Pb concentration in shoots and roots of plants under Pb stress. The
      microscopic examination indicated that application of exogenous H2S enabled a
      clean mesophyll cell having a well developed chloroplast with thylakoid membranes
      and starch grains. A number of modifications could be observed in root tip cell
      i.e. mature mitochondria, long endoplasmic reticulum and golgibodies under
      combined application of H2S and Pb. On the basis of these findings, it can be
      concluded that application of exogenous H2S has a protective role on plant
      growth, net photosynthesis rate and ultrastructural changes in B. napus plants
      under high Pb exposures.

PMID- 24580819
TI  - Aquatic ecotoxicity effect of engineered aminoclay nanoparticles.
AB  - In the present study the short term aquatic ecotoxicity of water-solubilized
      aminoclay nanoparticles (ANPs) of ~51+/-31 nm average hydrodynamic diameter was
      characterized. An ecotoxicological evaluation was carried out utilizing standard
      test organisms of different phyla and trophic levels namely the eukaryotic
      microalga Pseudokirchneriella subcapitata, the crustacean Daphnia magna and the
      bioluminescent marine bacteria Vibrio fisheri. The effective inhibitory
      concentration (EC50) with 95% confidence limits for the microalga was 1.29 mg/L
      (0.72-1.82) for the average growth rate and 0.26 mg/L (0.23-0.31) for the cell
      yield. The entrapping of algal cells in aggregates of ANP may play a major role
      in the growth inhibition of algae P. subcapitata. No inhibition was observed for
      V. fisheri up to 25,000 mg/L (no observed effect concentration; NOEC). For D.
      magna no immobilization was observed in a limit test with 100 mg/L in 24 h while
      in 48 h a single animal was immobilized (5% inhibition). Correspondingly, the
      NOEC of ANP in 24 h was 100 mg/L and the lowest observed effect concentration
      (LOEC) for 48 h was 100 mg/L. Therefore it can be considered to use ANP as an
      algal-inhibition agent at concentrations <100 mg/L without affecting or only
      mildly affecting other organisms including zooplanktons, but further studies on
      the environmental fate and chronic toxicity of ANP is needed to confirm this.

PMID- 24580820
TI  - Potential environmental toxicity from hemodialysis effluent.
AB  - Understanding the toxicity of certain potentially toxic compounds on various
      aquatic organisms allows to assess the impact that these pollutants on the
      aquatic biota. One source of pollution is the wastewater from hemodialysis. The
      process of sewage treatment is inefficient in inhibition and removal of
      pathogenic bacteria resistant to antibiotics in this wastewater. In many
      countries, such as Brazil, during emergencies, sewage and effluents from
      hospitals are often dumped directly into waterways without any previous
      treatment. The objective of this study was to characterize the effluents
      generated by hemodialysis and to assess the degree of acute and chronic
      environmental toxicity. The effluents of hemodialysis showed high concentrations
      of nitrites, phosphates, sulfates, ammonia, and total nitrogen, as well as
      elevated conductivity, turbidity, salinity, biochemical and chemical oxygen
      demand, exceeding the thresholds defined in the CONAMA Resolution 430. The
      samples showed acute toxicity to the green flagellate Euglena gracilis affecting
      different physiological parameters used as endpoints in an automatic bioassay
      such as motility, precision of gravitational orientation (r-value), compactness,
      upward movement, and alignment, with mean EC50 values of recalculate as 76.90
      percent (+/-4.68 percent) of the undiluted effluents. In tests with Daphnia
      magna, the acute toxicity EC50 was 86.91 percent (+/-0.39 percent) and a NOEC
      value of 72.97 percent and a LEOC value 94.66 percent. 

PMID- 24580821
TI  - Ecotoxicity analysis of cholinium-based ionic liquids to Vibrio fischeri marine
      bacteria.
AB  - Cholinium-based ionic liquids are quaternary ammonium salts with a wide range of
      potential industrial applications. Based on the fact that the cholinium is a
      complex B vitamin and widely used as food additive, the cholinium-based ionic
      liquids are generically regarded as environmentally "harmless" and thus, accepted
      as "non-toxic", although their ecotoxicological profile is poorly known. This
      work provides new ecotoxicological data for ten cholinium-based salts and ionic
      liquids, aiming to extend the surprisingly restricted body of knowledge about the
      ecotoxicity of this particular family and to gain insight on the toxicity
      mechanism of these compounds. The results reported here show that not all the
      cholinium tested can be considered harmless towards the test organism adopted.
      Moreover, the results suggest that the cholinium family exhibits a different
      mechanism of toxicity as compared to the imidazolium ionic liquids previously
      described in the literature. 

PMID- 24580822
TI  - Dynamics of rhizosphere properties and antioxidative responses in wheat (Triticum
      aestivum L.) under cadmium stress.
AB  - In this study, we performed a rhizobox experiment to examine the dynamic changes
      in the rhizosphere properties and antioxidant enzyme responses of Triticum
      aestivum L. under three levels of cadmium stress. A set of micro-techniques
      (i.e., Rhizobox and Rhizon SMS) were applied for the dynamically non-destructive
      collection of the rhizosphere soil solution to enable the observation at a high
      temporal resolution. The dynamics of soluble cadmium and dissolved organic carbon
      (DOC) in the rhizosphere soil solutions of the Triticum aestivum L. were
      characterised by the sequence week 0 after sowing (WAS0)<3 weeks after sowing
      (WAS3)<10 weeks after sowing (WAS10), whereas the soil solution pH was found to
      follow an opposite distribution pattern. Systematically, both superoxide
      dismutase (SOD) and catalase (CAT) activities in the leaves of the Triticum
      aestivum L. increased concomitantly with increasing cadmium levels (p>0.05) and
      growth duration (p<0.05), whilst ascorbate peroxidase (APX) activity was induced
      to an elevated level at moderate cadmium stress with a decrease at high cadmium
      stress (p>0.05). These results suggested the enhancement of DOC production and
      the greater antioxidant enzyme activities were two important protective
      mechanisms of Triticum aestivum L. under cadmium stress, whereas rhizosphere
      acidification might be an important mechanism for the mobilisation of soil
      cadmium. The results also revealed that plant-soil interactions strongly
      influence the soil solution chemistry in the rhizosphere of Triticum aestivum L.,
      that, in turn, can stimulate chemical and biochemical responses in the plants. In
      most cases, these responses to cadmium stress were sensitive and might allow us
      to develop strategies for reducing the risks of the cadmium contamination to crop
      production. 

PMID- 24580823
TI  - Evidence of oxidative stress in wild freshwater mussels (Lasmigona costata)
      exposed to urban-derived contaminants.
AB  - The physiological effect of complex mixtures of anthropogenic contaminants on
      aquatic organisms is not well understood. This study employed a suite of sub
      cellular biomarkers and general health measurements to assess the effect of urban
      derived contaminants on wild freshwater mussels. Adult Lasmigona costata were
      collected from four sites in the Grand River (ON, Canada) that receive
      incremental amounts of municipal wastewater effluents and road runoff. Biomarkers
      of metal exposure, oxidative stress, and general health were examined in the
      gills of wild mussels. Concentrations of nine metals as well as the metal-binding
      protein, metallothionein (MT), were significantly higher (p<0.05) in mussels
      living downstream of the urban area. For example the concentrations of Pb, Cr and
      Zn were five-fold, and Ag more than 20 fold higher in mussels collected
      downstream of 11 municipal wastewater treatment plants and four cities compared
      to levels in upstream mussels. Downstream mussels showed evidence of oxidative
      stress, such that lipid peroxidation (LPO) (as thiobarbiturate reactive
      substances) was significantly elevated and the antioxidant capacity against
      peroxyl radicals (ACAP) was significantly decreased (p<0.01) in downstream
      mussels compared to upstream mussels. Regarding general health indicators,
      although gill lipid concentrations were similar across sites, protein
      concentration was significantly (p<0.001) higher in mussels collected from the
      upstream reference site compared to all downstream sites. The trends observed
      indicate that there are physiological effects in mussels associated with chronic
      exposure to complex urban inputs and that some biomarkers respond to municipal
      wastewater effluent and road runoff exposure in a cumulative manner. The observed
      oxidative stress response (ACAP) along with the elevation in MT, suggest that
      even though the defense mechanisms in the chronically exposed mussels have been
      activated, there is still an excess of reactive oxygen species that result in
      oxidative damage. The physiological effects of exposure reported in this study
      correspond with previously reported whole-organism impacts and declines in
      freshwater mussel populations in the urban-impacted region of this watershed. 

PMID- 24580824
TI  - Hypoxia disrupts gene modulation along the brain-pituitary-gonad (BPG)-liver
      axis.
AB  - Hypoxia alters sex hormone concentrations leading to reproductive impairment in
      fish; however the mechanisms underlying these effects remain largely unknown.
      Using zebrafish (Danio rerio), this study is the first to demonstrate that
      hypoxia causes endocrine disruption by simultaneously acting on multiple targets
      along the brain-pituitary-gonadal (BPG)-liver axis in fish. Alterations in the
      expression of key genes associated with reproductive endocrine pathways in the
      brain (sGnRH), pituitary (FSHbeta and LHbeta), gonads (FSH-R, LH-R, HMGR, StAR,
      CYP19A, CYP11A, CYP11beta and 20beta-HSD), and liver were correlated with
      significant reductions of estradiol in females and testosterone in males. Hypoxia
      also induced sex-specific and tissue-specific changes in the expression of
      estrogen, androgen, and membrane progestin receptors along the BPG axis,
      suggesting disruption of the feedback and synchronization of hormone signals.
      Furthermore, the hypoxia-induced upregulation of hepatic sex hormone-binding
      globulin suggests an increase in hormone transport and reduced bioavailability in
      blood, while upregulation of hepatic CYP3A65 and CYP1A in females suggests an
      increase in estrogen biotransformation and clearance. Given that the regulation
      of reproductive hormones and the BPG-liver axis are highly conserved, this study
      provides new insights into the hypoxia-induced endocrine disrupting mechanisms
      and reproductive impairment in other vertebrates. 

PMID- 24580825
TI  - A multiphase analysis of partitioning and hazard index characteristics of
      siloxanes in biosolids.
AB  - Siloxanes are widely used in personal care and industrial products due to their
      soft texture, low surface tension, thermal stability, antimicrobial and
      hydrophobic properties, among other characteristics. As a result, they are
      released to gas phase during waste decompositions and found in biogas at
      landfills and digester gas at wastewater treatment facilities. The objectives of
      this study were to investigate the release of siloxanes in aqueous and gaseous
      phase as well as in biosolids in a local wastewater treatment facility. The
      formation reactions were estimated using first order kinetics for commonly found
      siloxanes (L3, D3, D4, D5 and D6) during waste decomposition. Expected
      concentrations and the risk factors of exposure to siloxanes were evaluated based
      on the initial concentrations, partitioning characteristics and persistence
      parameter. D4 and D5 presented the highest initial gaseous phase concentrations
      of 5000 and 1800 MUg/m(3) respectively. Based on first order kinetics, partition
      coefficients and initial concentrations, the hazards potentials were largest for
      D4 in both liquid phase and biosolids while D6 poses the highest risk in gaseous
      phase.

PMID- 24580826
TI  - Risk assessment of arsenic and other metals via atmospheric particles, and
      effects of atmospheric exposure and other demographic factors on their
      accumulations in human scalp hair in urban area of Guangzhou, China.
AB  - Eighty-eight scalp hair samples were collected from Guangzhou (GZ) urban
      population (15-65 years) to investigate the accumulation of As and other metals
      (Cr, Mn, Ni, Cu, Zn, Cd, Sn, Sb, Hg and Pb). Demographic information, including
      body weight, height, age, gender, habits of smoking and drinking, types of
      drinking water, duration of stay in GZ, days of stay in GZ per year (days/year),
      and hours spent in indoor environment per day (h/day), were also recorded during
      hair sampling to refine the uncertainty of risk assessment derived from exposures
      to elements via dust and airborne particles. No significant non-carcinogenic risk
      was found. However, the cancer risks of Cr and As for both ingestion and
      inhalation exceeded the most tolerable regulated level (1.0*10(-6)). The
      environmental exposures to urban dust and airborne particles were observed
      significantly correlated to accumulations of Cd (R=0.306, p=0.005) and Ni
      (R=0.333, p=0.002) in scalp hair. Furthermore, the hair burden of elements was
      also significantly (p<0.05) dependent on gender (Mn, Ni, Zn, As, Sn and Hg), age
      (Cr, As, Cd and Hg), duration of stay in GZ (Hg) as well as nutritional and
      physical status, reflected by BMI and BSA (Cr, Ni, Cd, Sb and Hg). Nutritional
      and physical status was observed as the exclusive important factor influencing As
      speciation in human scalp hair. However, habits of smoking and alcohol drinking
      as well as types of drinking water were not identified as the significant
      influencing factors on any element (p>0.05). 

PMID- 24580827
TI  - The combined effects of atrazine and lead (Pb): relative microbial activities and
      herbicide dissipation.
AB  - The experiment was conducted to investigate the effects of single and combined
      pollution from different concentrations of atrazine (field rate, FR, 2.0 mg kg(
      1) and 5 times FR, 10 mg kg(-1)) and lead (Pb) (300 mg kg(-1) and 600 mg kg(-1))
      on enzyme activity, basal soil respiration (BSR), and net nitrogen (N)
      mineralization (NNM) in soil after exposure for 0, 7, 14, 21, and 28 days. In
      addition, residual atrazine was measured in the samples of combined
      contamination. Results showed that the notable effects of either or both
      contaminants on the microbial activity and biological processes. Enzyme activity
      data demonstrated that the order of sensitivity to contamination was
      urease>invertase>catalase. BSR was strongly stimulated by atrazine/Pb at the
      early exposure (0-7 days for single contaminant and 7-14 days for combined
      contaminants). The stimulation effects on BSR were higher at low concentrations
      of the contamination (FR and Pb300). The combined treatments of 5FR+Pb600 inhibit
      BSR and NNM. Overall, the parameters associated with N cycling (urease and NNM)
      were more sensitive than others. Both Pb concentrations (300 and 600 mg/kg) had
      little influence on the dissipation of high concentrations of atrazine (5FR)
      during the 28-day-incubation. This study has provided useful information on
      potential ecotoxicology effects of combined contamination of atrazine and Pb on
      relative microbial biological process.

PMID- 24580828
TI  - The role of donor-specific HLA alloantibodies in liver transplantation.
AB  - The impact of donor-specific HLA alloantibodies (DSA) on short- and long-term
      liver transplant outcome is not clearly defined. While it is clear that not all
      levels of allosensitization produce overt clinical injury, and that liver
      allografts possess some degree of alloantibody resistance, alloantibody-mediated
      adverse consequences are increasingly being recognized. To better define the
      current state of this topic, we assembled experts to provide insights, explore
      controversies and develop recommendations for future research on the consequences
      of DSA in liver transplantation. This article summarizes the proceedings of this
      inaugural meeting. Several insights emerged. Acute antibody-mediated rejection
      (AMR), although rarely diagnosed, is increasingly understood to overlap with T
      cell-mediated rejection. Isolated liver allograft recipients are at increased
      risk of early allograft immunologic injury when preformed DSA are high titer and
      persist posttransplantation. Persons who undergo simultaneous liver-kidney
      transplantation are at risk of renal AMR when Class II DSA persist
      posttransplantation. Other under-appreciated DSA associations include ductopenia
      and fibrosis, plasma cell hepatitis, biliary strictures and accelerated fibrosis
      associated with recurrent liver disease. Standardized DSA testing and diagnostic
      criteria for both acute and chronic AMR are needed to distil existing
      associations into etiological processes in order to develop responsive
      therapeutic strategies. 

PMID- 24580830
TI  - Continuous Professional Competence (CPC) for Irish paramedics and advanced
      paramedics: a national study.
AB  - BACKGROUND: Internationally, continuing professional competence (CPC) is an
      increasingly important issue for all health professionals. With the imminent
      introduction of a CPC framework for paramedics and advanced paramedics (APs) in
      Ireland, this paper aims to identify factors that will inform the implementation
      of this CPC framework by seeking stakeholder input into the development of a CPC
      model for use by the regulatory body. Our secondary objective is to determine the
      attitudes of registrants towards CPC and what they consider as optimal
      educational outcomes and activities, for the purposes of CPC. METHODS: All
      paramedics and APs registered in Ireland (n = 1816) were invited by email to
      complete an anonymous on-line survey. The study instrument was designed based on
      CPD questionnaires used by other healthcare professions. Quantitative and
      qualitative analyses were performed. RESULTS: The overall response rate was 43%
      (n = 789), with 82% of APs and 38% of paramedics participating. Eighty-nine per
      cent agreed that registration was of personal importance; 74% agreed that
      evidence of CPC should be maintained and 39% believed that persistent failure to
      meet CPC requirements should mandate denial of registration. From a pre
      determined list of activities, respondents indicated practical training scenarios
      (94%), cardiac re-certification (92%), e-learning supplemented by related
      practice (90%) and training with simulation manikins (88%) were most relevant,
      while e-learning alone (36%), project work (27%) and reading journal articles
      (24%) were least relevant. CONCLUSIONS: Irish Paramedics and APs are supportive
      of CPC linked with their professional development and registration. Blended
      learning, involving evidence of patient contact, team-based learning and
      practical skills are preferred CPC activities.

PMID- 24580829
TI  - Host bone marrow-derived IL-12 enhances donor T cell engraftment in a mouse model
      of bone marrow transplantation.
AB  - BACKGROUND: Donor cell engraftment is critical for the success of allogeneic bone
      marrow transplants. Graft failure is a result of donor cells either failing to
      engraft initially or being eliminated at later time points. Donor cell
      engraftment is facilitated by donor T cells, which eliminate residual host hemato
      lymphoid effector cells such as NK cells and T cells. METHODS: We aimed to
      explore the role of host hematopoietic cell derived IL-12 on donor cell
      engraftment in a murine model of BMT. We established radiation chimeras by
      transplanting C57BL6/J (B6) mice with BM from either congenic B6 mice or IL-12p40
      KO mice. These WT -> WT or IL-12 KO -> WT chimeras then underwent a secondary
      transplant with allogeneic (FVB) BM. Survival, engraftment, donor T cell
      expansion, cytokine production by donor T cells, as well as expression of
      stimulatory markers on donor T cells was analyzed. RESULTS: Mice whose residual
      host hematopoietic cells were capable of producing IL-12 had modestly higher
      survival, higher donor T cell engraftment, and significantly higher donor
      erythroid engraftment. We have also found that an increased number of donor T
      cells in IL-12 KO -> WT chimeras have a regulatory phenotype, expressing FoxP3,
      producing lower levels of TNF-alpha, higher levels of IL-10, and expressing
      higher levels of ICOS as well as PD-1 on CD4+ T cells. CONCLUSIONS: To our
      knowledge, this is the first report of a beneficial role of IL-12 production by
      host cells in the context of bone marrow engraftment in a murine model of BMT.
      These findings support the clinical use of exogenous IL-12 for use in settings
      where graft failure is of concern.

PMID- 24580831
TI  - Estimating the under-reporting of norovirus illness in Germany utilizing enhanced
      awareness of diarrhoea during a large outbreak of Shiga toxin-producing E. coli
      O104:H4 in 2011--a time series analysis.
AB  - BACKGROUND: Laboratory-confirmed norovirus illness is reportable in Germany since
      2001. Reported case numbers are known to be undercounts, and a valid estimate of
      the actual incidence in Germany does not exist. An increase of reported norovirus
      illness was observed simultaneously to a large outbreak of Shiga toxin-producing
      E. coli O104:H4 in Germany in 2011--likely due to enhanced (but not complete)
      awareness of diarrhoea at that time. We aimed at estimating age- and sex-specific
      factors of that excess, which should be interpretable as (minimal) under
      reporting factors of norovirus illness in Germany. METHODS: We used national
      reporting data on laboratory-confirmed norovirus illness in Germany from calendar
      week 31 in 2003 through calendar week 30 in 2012. A negative binomial time series
      regression model was used to describe the weekly counts in 8?2 age-sex strata
      while adjusting for secular trend and seasonality. Overall as well as age- and
      sex-specific factors for the excess were estimated by including additional terms
      (either an O104:H4 outbreak period indicator or a triple interaction term between
      outbreak period, age and sex) in the model. RESULTS: We estimated the overall
      under-reporting factor to be 1.76 (95% CI 1.28-2.41) for the first three weeks of
      the outbreak before the outbreak vehicle was publicly communicated. Highest under
      reporting factors were here estimated for 20-29 year-old males (2.88, 95% CI 2.01
      4.11) and females (2.67, 95% CI 1.87-3.79). Under-reporting was substantially
      lower in persons aged <10 years and 70 years or older. CONCLUSIONS: These are the
      first estimates of (minimal) under-reporting factors for norovirus illness in
      Germany. They provide a starting point for a more detailed investigation of the
      relationship between actual incidence and reporting incidence of norovirus
      illness in Germany.

PMID- 24580832
TI  - Colorado potato beetle (Coleoptera) gut transcriptome analysis: expression of RNA
      interference-related genes.
AB  - In the search for new methods of pest control, the potential of RNA interference
      (RNAi) is being explored. Because the gut is the first barrier for the uptake of
      double-stranded (ds)RNA, pyrosequencing of the gut transcriptome is a powerful
      tool for obtaining the necessary sequences for specific dsRNA-mediated pest
      control. In the present study, a dataset representing the gut transcriptome of
      the Colorado potato beetle (CPB; Leptinotarsa decemlineata) was generated and
      analysed for the presence of RNAi-related genes. Almost all selected genes that
      were implicated in silencing efficiency at different levels in the RNAi pathway
      (core machinery, associated intracellular factors, dsRNA uptake, antiviral RNAi,
      nucleases), which uses different types of small RNA (small interfering RNA,
      microRNA and piwi-RNA), were expressed in the CPB gut. Although the database is
      of lower quality, the majority of the RNAi genes are also found to be present in
      the gut transcriptome of the tobacco hornworm [TH; Manduca sexta (19 out of 35
      genes analysed)]. The high quality of the CPB transcriptome database will lay the
      foundation for future gene expression and functional studies regarding the gut
      and RNAi. 

PMID- 24580833
TI  - Division in Escherichia coli is triggered by a size-sensing rather than a timing
      mechanism.
AB  - BACKGROUND: Many organisms coordinate cell growth and division through size
      control mechanisms: cells must reach a critical size to trigger a cell cycle
      event. Bacterial division is often assumed to be controlled in this way, but
      experimental evidence to support this assumption is still lacking. Theoretical
      arguments show that size control is required to maintain size homeostasis in the
      case of exponential growth of individual cells. Nevertheless, if the growth law
      deviates slightly from exponential for very small cells, homeostasis can be
      maintained with a simple 'timer' triggering division. Therefore, deciding whether
      division control in bacteria relies on a 'timer' or 'sizer' mechanism requires
      quantitative comparisons between models and data. RESULTS: The timer and sizer
      hypotheses find a natural expression in models based on partial differential
      equations. Here we test these models with recent data on single-cell growth of
      Escherichia coli. We demonstrate that a size-independent timer mechanism for
      division control, though theoretically possible, is quantitatively incompatible
      with the data and extremely sensitive to slight variations in the growth law. In
      contrast, a sizer model is robust and fits the data well. In addition, we tested
      the effect of variability in individual growth rates and noise in septum
      positioning and found that size control is robust to this phenotypic noise.
      CONCLUSIONS: Confrontations between cell cycle models and data usually suffer
      from a lack of high-quality data and suitable statistical estimation techniques.
      Here we overcome these limitations by using high precision measurements of tens
      of thousands of single bacterial cells combined with recent statistical inference
      methods to estimate the division rate within the models. We therefore provide the
      first precise quantitative assessment of different cell cycle models.

PMID- 24580834
TI  - Tobacco smoking in Mongolia: findings of a national knowledge, attitudes and
      practices study.
AB  - BACKGROUND: In 2009, 48% of males aged 15 or over in Mongolia consumed tobacco,
      placing Mongolia among the countries with the highest prevalence of male smokers
      in the world. Importantly, tobacco use is one of the four major risk factors
      contributing to the global burden of non-communicable diseases (NCDs) - the
      leading cause of mortality in Mongolia. However, the knowledge, attitudes and
      practices of the Mongolian population with regards to smoking are largely
      unmeasured. In this context, a national NCDs knowledge, attitudes and practices
      survey focusing, among other things, on NCD risk factors was implemented in
      Mongolia in late 2010 to complement the previous WHO STEPwise approach to
      Surveillance Survey (STEPS) findings from 2009. This publication explores the
      smoking-related findings of the Knowledge, Attitudes and Practices Survey (KAPS).
      METHODS: A nationally representative sample size was calculated using
      methodologies aligned with the WHO STEPS surveys. As a result, 3450 people from
      across Mongolia were selected using a multi-stage, random cluster sampling method
      from permanent residents aged between 15 and 64 years. The KAP survey
      questionnaire was interviewer-administered on a door-to-door basis. RESULTS: In
      Mongolia at 2010, 46.3% of males and 6.8% of females were smokers. This practice
      was especially dominant among males and urban dwellers (MOR 2.2), and more so
      among the middle-aged (45-54) (MOR 2.1) while still displaying a high prevalence
      among Mongolian youth (15.5%). The probability of smoking was independent of the
      level of education. Although the level of awareness of the health hazards related
      to tobacco smoking was generally very high in the population, this was influenced
      by the level of education as more people with a primary and secondary level of
      education believed that smoking at least one pack of cigarette per day was
      required to harm one's health (MOR 5.8 for primary education and 2.5 for
      secondary). Finally, this knowledge did not necessarily translate into a
      behavioural outcome as 15.5% of the population did not object to people smoking
      in their house, and especially so among males (MOR 4.1). CONCLUSION: The findings
      of this KAP survey corroborate the 2009 WHO STEPS Survey findings with regards to
      the prevalence of tobacco smoking in Mongolia. It identifies males, urban
      dwellers and Mongolian youth as groups that should be targeted by public health
      measures on tobacco consumption, while keeping in mind that higher levels of
      awareness of the harms caused by tobacco smoking do not necessarily translate
      into behavioural changes.

PMID- 24580835
TI  - Flap versus flapless procedure for ridge preservation in alveolar extraction
      sockets: a histological evaluation in a randomized clinical trial.
AB  - OBJECTIVE: The aim of this study was to evaluate and compare the histological and
      histomorphometric features of two different procedures carried out in extraction
      socket grafting; namely, the flapped and flapless technique. MATERIALS AND
      METHODS: Patients considered eligible for the study were randomized to receive
      tooth extraction and ridge preservation with the porcine bone and collagen
      membrane, with a full thickness mucoperiosteal flap and primary soft tissue
      closure (control group), or, with a flapless procedure and a secondary soft
      tissue closure (test group). After 3 months of healing, the surgical re-entry
      procedure was performed and implants were inserted in the test as well as in the
      control sites. Bone core samples were harvested from both groups and processed to
      be observed under light microscopy. Outcome variables were percentages of newly
      formed bone, residual graft particles and marrow spaces. RESULTS: Thirty-four
      patients were enrolled in the study. All of the scheduled implants were placed.
      Histological and histomorphometrical analyses did not report significant
      differences between the two groups (with P-values ranging from 0.690 to 0.917).
      The mean percentages of newly formed bone, soft tissues and residual grafted
      particles were 22.5 and 22.5%, 59.3 and 59.4%, and 18.6 and 18.2% respectively
      for flap and flapless approach. CONCLUSION: No histological and
      histomorphometrical differences were observed when comparing the flap and the
      flapless technique for tooth extraction and socket grafting procedures.

PMID- 24580836
TI  - Specific activation of the paralemniscal pathway during nociception.
AB  - Two main neuronal pathways connect facial whiskers to the somatosensory cortex in
      rodents: (i) the lemniscal pathway, which originates in the brainstem principal
      trigeminal nucleus and is relayed in the ventroposterior thalamic nucleus and
      (ii) the paralemniscal pathway, originating in the spinal trigeminal nucleus and
      relayed in the posterior thalamic nucleus. While lemniscal neurons are readily
      activated by whisker contacts, the contribution of paralemniscal neurons to
      perception is less clear. Here, we functionally investigated these pathways by
      manipulating input from the whisker pad in freely moving mice. We report that
      while lemniscal neurons readily respond to neonatal infraorbital nerve sectioning
      or whisker contacts in vivo, paralemniscal neurons do not detectably respond to
      these environmental changes. However, the paralemniscal pathway is specifically
      activated upon noxious stimulation of the whisker pad. These findings reveal a
      nociceptive function for paralemniscal neurons in vivo that may critically inform
      context-specific behaviour during environmental exploration. 

PMID- 24580838
TI  - Physiology and applied sciences in Nepal: 1st annual conference.
AB  - With the increasing number of medical schools in Nepal, there is an expected
      increase in the number of Nepalese physiologists. The first medical school was
      established in the 1970s. We report here about the first annual conference of
      Nepalese physiologists on 27-28 September 2013 organized by the Department of
      Clinical Physiology of the Nepalese Army Institute of Health Sciences (NAIHS) and
      Kathmandu University School of Medical Sciences (KUMS). Nepalese physiologists
      are trying to form their own physiological society. In this regard, NAIHS and
      KUMS have played an important role to bring physiologists from different parts of
      Nepal involved in teaching, learning, and research activities in medical schools.
      There were a number of foreign invitees (India, Israel, Italy, Japan, and
      Sweden). There were plenary presentations on the topics that are relevant in
      Nepal, e.g., high-altitude physiology and wilderness medicine. The final session
      of the conference was an open session meeting of Nepalese physiologists. There
      was an open interaction about establishing Nepalese Physiological Society. After
      much deliberation, there was an agreement to register the society in Kathmandu
      with the current ad hoc committee which will elect the first executive body of
      the society. 

PMID- 24580837
TI  - Clinical drug response can be predicted using baseline gene expression levels and
      in vitro drug sensitivity in cell lines.
AB  - We demonstrate a method for the prediction of chemotherapeutic response in
      patients using only before-treatment baseline tumor gene expression data. First,
      we fitted models for whole-genome gene expression against drug sensitivity in a
      large panel of cell lines, using a method that allows every gene to influence the
      prediction. Following data homogenization and filtering, these models were
      applied to baseline expression levels from primary tumor biopsies, yielding an in
      vivo drug sensitivity prediction. We validated this approach in three independent
      clinical trial datasets, and obtained predictions equally good, or better than,
      gene signatures derived directly from clinical data. 

PMID- 24580839
TI  - Proteomic analysis on effectors involved in BMP-2-induced osteogenic
      differentiation of beagle bone marrow mesenchymal stem cells.
AB  - OBJECTIVE: To identify the protein regulation profile of recombinant human bone
      morphogenetic protein-2 (rhBMP-2)-induced osteogenic differentiation in beagle
      bone marrow stem cells (BMSCs). METHODS: Beagle BMSCs were isolated and cultured
      with or without rhBMP-2. Two-dimensional gel electrophoresis was used to
      determine the differences in protein expression in rhBMP-2-induced and non
      induced BMSCs. Real-time PCR and western blotting analyses were used to verify
      the expression patterns of selected proteins. RESULTS: After the induction, the
      osteogenic differentiation of beagle BMSCs was activated successfully. Nine and
      11 proteins were found to be down- and up-regulated by rhBMP-2, respectively. The
      increase in Lim and SH3 domain protein 1(LASP1) and the decrease in ferritin were
      verified by real-time PCR and western blotting analyses. CONCLUSIONS: Among the
      20 rhBMP-2-regulated factors, there is empirical evidence supporting the
      involvement of LASP1 and ferritin in osteogenic differentiation. LASP1 plays an
      important role in the regulation of the activity of the cytoskeleton, and
      ferritin is an important molecule in cellular iron homeostasis. Further studies
      focused on these 20 proteins will help elucidate the molecular mechanism(s)
      through which rhBMP-2 induces osteogenic differentiation of BMSCs.

PMID- 24580840
TI  - Association of Trypanosoma cruzi infection with risk factors and
      electrocardiographic abnormalities in northeast Mexico.
AB  - BACKGROUND: American trypanosomiasis is a major disease and public health issue,
      caused by the protozoan parasite Trypanosoma cruzi. The prevalence of T. cruzi
      has not been fully documented, and there are few reports of this issue in Nuevo
      Leon. The aim of this study was to update the seroprevalence rate of T. cruzi
      infection, including an epidemiological analysis of the risk factors associated
      with this infection and an electrocardiographic (ECG) evaluation of those
      infected. METHODS: Sera from 2,688 individuals from 10 municipalities in the
      state of Nuevo Leon, Mexico, were evaluated using an enzyme-linked immunosorbent
      assay and an indirect hemagglutination assay. An ECG case-control study was
      performed in subjects seropositive for T. cruzi and the results were matched by
      sex and age to seronegative residents of the same localities. A univariate
      analysis with chi2 and Fisher's exact tests was used to determine the association
      between seropositivity and age (years), sex, and ECG changes. A multivariate
      analysis was then performed to calculate the odd ratios between T. cruzi
      seropositivity and the risk factors. RESULTS: The seropositive rate was 1.93%
      (52/2,688). In the ECG study, 22.85% (8/35) of the infected individuals exhibited
      ECG abnormalities. Triatoma gerstaeckeri was the only vector reported. The main
      risk factors were ceiling construction material (P <= 0.0024), domestic animals
      (P <= 0.0001), and living in rural municipalities (P <= 0.0025). CONCLUSIONS:
      These findings demonstrate a 10-fold higher prevalence of Chagas disease than
      previously reported (0.2%), which implies a serious public health threat in
      northeastern Mexico. The epidemiological profile established in this study
      differs from that found in the rest of Mexico, where human populations live in
      close proximity to domiciliary triatomines.

PMID- 24580841
TI  - A short-term treatment with tumor necrosis factor-alpha enhances stem cell
      phenotype of human dental pulp cells.
AB  - INTRODUCTION: During normal pulp tissue healing, inflammatory cytokines, such as
      tumor necrosis factor-alpha (TNF-alpha) or interleukins, act in the initial 48
      hours (inflammatory phase) and play important roles not only as chemo-attractants
      of inflammatory cells and stem/progenitor cells but also in inducing a cascade of
      reactions toward tissue regeneration or reparative dentin formation or both.
      Previous reports have shown that inflammatory cytokines regulate the
      differentiation capacity of dental pulp stem/progenitor cells (DPCs), but none
      has interrogated the impact of these cytokines on the stem cell phenotype of
      stem/progenitor cells. This study investigated the effects of a short-term
      treatment with TNF-alpha on the stem cell phenotype and differentiation ability
      of human DPCs. METHODS: An in vivo mouse model of pulp exposure was performed for
      analysis of expression of the mesenchymal stem cell marker CD146 in DPCs during
      the initial stage of inflammatory response. For in vitro studies, human DPCs were
      isolated and incubated with TNF-alpha for 2 days and passaged to eliminate TNF
      alpha completely. Analysis of stem cell phenotype was performed by quantification
      of cells positive for mesenchymal stem cell markers SSEA-4 (stage-specific
      embryonic antigen 4) and CD146 by flow cytometry as well as by quantitative
      analysis of telomerase activity and mRNA levels of OCT-4 and NANOG. Cell
      migration, colony-forming ability, and differentiation toward odontogenesis and
      adipogenesis were also investigated. RESULTS: The pulp exposure model revealed a
      strong staining for CD146 during the initial inflammatory response, at 2 days
      after pulp exposure. In vitro experiments demonstrated that a short-term (2-day)
      treatment of TNF-alpha increased by twofold the percentage of SSEA-4+ cells.
      Accordingly, STRO-1, CD146, and SSEA-4 protein levels as well as OCT-4 and NANOG
      mRNA levels were also significantly upregulated upon TNF-alpha treatment. A short
      term TNF-alpha treatment also enhanced DPC function, including the ability to
      form cell colonies, to migrate, and to differentiate into odontogenic and
      adipogenic lineages. CONCLUSIONS: A short-term treatment with TNF-alpha enhanced
      the stem cell phenotype, migration, and differentiation ability of DPCs.

PMID- 24580842
TI  - Active hiding of social information from information-parasites.
AB  - BACKGROUND: Coevolution between pairs of different kind of entities, such as
      providers and users of information, involves reciprocal selection pressures
      between them as a consequence of their ecological interaction. Pied flycatchers
      (Ficedula hypoleuca) have been shown to derive fitness benefits (larger clutches)
      when nesting in proximity to great tits (Parus major), presumably because they
      this way discover and obtain information about nesting sites. Tits suffer from
      the resulting association (smaller clutches). An arms race between the tits
      (information host) and the flycatchers (information parasite) could thus result.
      Great tits often cover eggs with nesting material before, but not during
      incubation. We hypothesized that one function of egg-covering could be a counter
      adaptation to reduce information parasitism by pied flycatchers. We predicted
      that tits should bring more new hair to cover their exposed eggs when a pied
      flycatcher is present near to tit nest than when a neutral (non-competing)
      species is present. We conducted decoy and playback experiment in Oulu and Turku,
      Finland. First, we removed and collected all the hair covering the tit eggs.
      Then, we measured how the perceived presence of flycatcher or waxwing (Bombycilla
      garrulus) affects tits' egg-covering by collecting and weighing the hair brought
      on the eggs and photographing the nest 24 h after the playback. RESULTS: Tits
      brought more hair into the nest and covered the eggs more carefully after
      flycatcher treatment, compared to waxwing treatment. We also found that the tits
      in Oulu (over 600 km to north from Turku) had more hair on the top of their eggs
      in general. CONCLUSIONS: Together, these results suggest that the counter
      adaptation function of egg-covering against information parasites may be an
      extension of original function to protect eggs from low temperatures.

PMID- 24580844
TI  - Stress induced telomere shortening: longer life with less mutations?
AB  - BACKGROUND: Mutations accumulate as a result of DNA damage and imperfect DNA
      repair machinery. In higher eukaryotes the accumulation and spread of mutations
      is limited in two primary ways: through p53-mediated programmed cell death and
      cellular senescence mediated by telomeres. Telomeres shorten at every cell
      division and cell stops dividing once the shortest telomere reaches a critical
      length. It has been shown that the rate of telomere attrition is accelerated when
      cells are exposed to DNA damaging agents. However the implications of this
      mechanism are not fully understood. RESULTS: With the help of in silico model we
      investigate the effect of genotoxic stress on telomere attrition and apoptosis in
      a population of non-identical replicating cells. When comparing the populations
      of cells with constant vs. stress-induced rate of telomere shortening we find
      that stress induced telomere shortening (SITS) increases longevity while reducing
      mutation rate. Interestingly, however, the effect takes place only when genotoxic
      stresses (e.g. reactive oxygen species due to metabolic activity) are distributed
      non-equally among cells. CONCLUSIONS: Our results for the first time show how non
      equal distribution of metabolic load (and associated genotoxic stresses) combined
      with stress induced telomere shortening can delay aging and minimize mutations.

PMID- 24580845
TI  - Kawasaki disease in a girl with Turner syndrome: a remarkable association.
AB  - We describe a girl with Turner syndrome, a genetic disorder of the X chromosome
      in a phenotypic female at increased risk of autoimmune and immunological
      diseases, who developed Kawasaki disease at the age of four years. Given the
      possible relationship between these two disorders, we recommend suspecting
      Kawasaki disease in patients with Turner syndrome who present with persistent
      fever of unknown origin and who are not responsive to antibiotic therapy.
      Attention should be given to this phenomenon, as patients with Turner syndrome
      are themselves at higher risk of cardiovascular defects. Further studies are
      needed to better clarify this issue.

PMID- 24580846
TI  - Immune activation despite suppressive highly active antiretroviral therapy is
      associated with higher risk of viral blips in HIV-1-infected individuals.
AB  - OBJECTIVES: Viral blips are thought to represent random biological variations
      around a steady state of residual HIV viraemia and to lack clinical significance.
      We aimed to assess the association of immune activation and the occurrence of
      blips. METHODS: HIV-infected patients from our out-patient cohort who developed a
      blip after having been on fully suppressive highly active antiretroviral therapy
      (HAART) for at least 180 days were matched with patients without blips according
      to duration of complete viral suppression (CVS), age, sex and Centers for Disease
      Control and Prevention (CDC) stage. Frequencies of CD3(+), CD3(+) CD4(+), CD3(+)
      CD8(+), CD3(+) HLA-DR(+), CD4(+) CD45RA(+), CD16(+) CD56(+) CD3(-) and CD19(+)
      cells, as well as C-reactive protein (CRP) levels and clinical parameters, were
      included in conditional logistic regression models. Adherence to HAART was
      assessed by measuring prescribed nonnucleoside reverse transcriptase inhibitor
      (NNRTI) or protease inhibitor (PI) plasma levels in a sample of 57 patients.
      RESULTS: Eighty-two patients with viral blip were matched with 82 controls from
      the same cohort. The mean age was 47.2 years [standard deviation (SD) 12.1
      years], 80.5% of patients were male and 42.7% had CDC stage C disease. Viral
      blips occurred after a median of 14 months [interquartile range (IQR) 8-34
      months] of CVS. In the logistic regression, activated CD3(+) HLA-DR(+)
      lymphocytes [odds ratio (OR) 1.25 per 100 cells/MUL; 95% confidence interval (CI)
      1.02-1.54; P = 0.03] were significantly associated with blips and there was a
      trend for an association of longer time on HAART with blips (OR 1.31 per year;
      95% CI 0.96-1.78; P = 0.09). No between-group difference regarding subtherapeutic
      drug levels was found (P = 0.46). CONCLUSIONS: The occurrence of viral blips
      after suppressive HAART was associated with elevated markers of T-cell
      activation. Blips may identify a subset of patients with higher immune activation
      and increased risk for HIV disease progression.

PMID- 24580843
TI  - Everolimus inhibits anti-HLA I antibody-mediated endothelial cell signaling,
      migration and proliferation more potently than sirolimus.
AB  - Antibody (Ab) crosslinking of HLA I molecules on the surface of endothelial cells
      triggers proliferative and pro-survival intracellular signaling, which is
      implicated in the process of chronic allograft rejection, also known as
      transplant vasculopathy (TV). The purpose of this study was to investigate the
      role of mammalian target of rapamycin (mTOR) in HLA I Ab-induced signaling
      cascades. Everolimus provides a tool to establish how the mTOR signal network
      regulates HLA I-mediated migration, proliferation and survival. We found that
      everolimus inhibits mTOR complex 1 (mTORC1) by disassociating Raptor from mTOR,
      thereby preventing class I-induced phosphorylation of mTOR, p70S6K, S6RP and 4E
      BP1, and resultant class I-stimulated cell migration and proliferation.
      Furthermore, we found that everolimus inhibits class I-mediated mTORC2 activation
      (1) by disassociating Rictor and Sin1 from mTOR; (2) by preventing class I
      stimulated Akt phosphorylation and (3) by preventing class I-mediated ERK
      phosphorylation. These results suggest that everolimus is more effective than
      sirolimus at antagonizing both mTORC1 and mTORC2, the latter of which is critical
      in endothelial cell functional changes leading to TV in solid organ
      transplantation after HLA I crosslinking. Our findings point to a potential
      therapeutic effect of everolimus in prevention of chronic Ab-mediated rejection. 

PMID- 24580848
TI  - Aldehyde reductase activity in the antennae of Helicoverpa armigera.
AB  - In the present study, we identified two aldehyde reductase activities in the
      antennae of Helicoverpa species, NADH and NADPH-dependent activity. We expressed
      one of these proteins of H. armigera, aldo-keto reductase (AKR), which bears 56%
      identity to bovine aldose reductase, displays a NADPH-dependent activity and is
      mainly expressed in the antennae of adults. Whole-mount immunostaining showed
      that the enzyme is concentrated in the cells at the base of chemosensilla and in
      the nerves. The enzyme activity of H. armigera AKR is markedly different from
      those of mammalian enzymes. The best substrates are linear aliphatic aldehydes of
      8-10 carbon atoms, but not hydroxyaldehydes. Both pheromone components of H.
      armigera, which are unsaturated aldehydes of 16 carbons, are very poor
      substrates. Unlike mammalian AKRs, the H. armigera enzyme is weakly affected by
      common inhibitors and exhibits a different behaviour from the action of thiols. A
      model of the enzyme suggests that the four cysteines are in their reduced form,
      as are the seven cysteines of mammalian enzymes. The occurrence of orthologous
      proteins in other insect species, that do not use aldehydes as pheromones,
      excludes the possibility of classifying this enzyme among the pheromone-degrading
      enzymes, as has been previously described in other insect species. 

PMID- 24580847
TI  - Research across the disciplines: a road map for quality criteria in empirical
      ethics research.
AB  - BACKGROUND: Research in the field of Empirical Ethics (EE) uses a broad variety
      of empirical methodologies, such as surveys, interviews and observation,
      developed in disciplines such as sociology, anthropology, and psychology. Whereas
      these empirical disciplines see themselves as purely descriptive, EE also aims at
      normative reflection. Currently there is literature about the quality of
      empirical research in ethics, but little or no reflection on specific
      methodological aspects that must be considered when conducting interdisciplinary
      empirical ethics. Furthermore, poor methodology in an EE study results in
      misleading ethical analyses, evaluations or recommendations. This not only
      deprives the study of scientific and social value, but also risks ethical
      misjudgement. DISCUSSION: While empirical and normative-ethical research projects
      have quality criteria in their own right, we focus on the specific quality
      criteria for EE research. We develop a tentative list of quality criteria--a
      "road map"--tailored to interdisciplinary research in EE, to guide assessments of
      research quality. These quality criteria fall into the categories of primary
      research question, theoretical framework and methods, relevance,
      interdisciplinary research practice and research ethics and scientific ethos.
      SUMMARY: EE research is an important and innovative development in bioethics.
      However, a lack of standards has led to concerns about and even rejection of EE
      by various scholars. Our suggested orientation list of criteria, presented in the
      form of reflective questions, cannot be considered definitive, but serves as a
      tool to provoke systematic reflection during the planning and composition of an
      EE research study. These criteria need to be tested in different EE research
      settings and further refined.

PMID- 24580849
TI  - A chitosan-polypyrrole magnetic nanocomposite as MU-sorbent for isolation of
      naproxen.
AB  - An extracting medium based on chitosan-polypyrrole (CS-PPy) magnetic
      nanocomposite was synthesized by chemical polymerization of pyrrole at the
      presence of chitosan magnetic nanoparticles (CS-MNPs) for micro-solid phase
      extraction. In this work, magnetic nanoparticles, the modified CS-MNPs and
      different types of CS-PPy magnetic nanocomposites were synthesized. Extraction
      efficiency of the CS-PPy magnetic nanocomposite was compared with the CS-MNPs and
      Fe3O4 nanoparticles for the determination of naproxen in aqueous samples, via
      quantification by spectrofluorimetry. The scanning electron microscopy images
      obtained from all the prepared nanocomposites revealed that the CS-PPy magnetic
      nanocomposite possess more porous structure. Among different synthesized magnetic
      nanocomposites, CS-PPy magnetic nanocomposite showed a prominent efficiency.
      Influencing parameters on the morphology of CS-PPy magnetic nanocomposite such as
      weight ratio of components was also assayed. In addition, effects of different
      parameters influencing the extraction efficiency of naproxen including desorption
      solvent, desorption time, amount of sorbent, ionic strength, sample pH and
      extraction time were investigated and optimized. Under the optimum condition, a
      linear calibration curve in the range of 0.04-10 MUg mL(-1) (R(2)=0.9996) was
      obtained. The limits of detection (3Sb) and limits of quantification (10Sb) of
      the method were 0.015 and 0.04 MUg mL(-1) (n=3), respectively. The relative
      standard deviation for water sample spiked with 0.1 MUg mL(-1) of naproxen was 3%
      (n=5) and the absolute recovery was 92%. The applicability of method was extended
      to the determination of naproxen in tap water, human urine and plasma samples.
      The relative recovery percentages for these samples were in the range of 56-99%.

PMID- 24580850
TI  - A new kernel discriminant analysis framework for electronic nose recognition.
AB  - Electronic nose (e-Nose) technology based on metal oxide semiconductor gas sensor
      array is widely studied for detection of gas components. This paper proposes a
      new discriminant analysis framework (NDA) for dimension reduction and e-Nose
      recognition. In a NDA, the between-class and the within-class Laplacian scatter
      matrix are designed from sample to sample, respectively, to characterize the
      between-class separability and the within-class compactness by seeking for
      discriminant matrix to simultaneously maximize the between-class Laplacian
      scatter and minimize the within-class Laplacian scatter. In terms of the linear
      separability in high dimensional kernel mapping space and the dimension reduction
      of principal component analysis (PCA), an effective kernel PCA plus NDA method
      (KNDA) is proposed for rapid detection of gas mixture components by an e-Nose.
      The NDA framework is derived in this paper as well as the specific
      implementations of the proposed KNDA method in training and recognition process.
      The KNDA is examined on the e-Nose datasets of six kinds of gas components, and
      compared with state of the art e-Nose classification methods. Experimental
      results demonstrate that the proposed KNDA method shows the best performance with
      average recognition rate and total recognition rate as 94.14% and 95.06% which
      leads to a promising feature extraction and multi-class recognition in e-Nose. 

PMID- 24580851
TI  - Multivariate curve resolution based chromatographic peak alignment combined with
      parallel factor analysis to exploit second-order advantage in complex
      chromatographic measurements.
AB  - In the present contribution, a new combination of multivariate curve resolution
      correlation optimized warping (MCR-COW) with trilinear parallel factor analysis
      (PARAFAC) is developed to exploit second-order advantage in complex
      chromatographic measurements. In MCR-COW, the complexity of the chromatographic
      data is reduced by arranging the data in a column-wise augmented matrix,
      analyzing using MCR bilinear model and aligning the resolved elution profiles
      using COW in a component-wise manner. The aligned chromatographic data is then
      decomposed using trilinear model of PARAFAC in order to exploit pure
      chromatographic and spectroscopic information. The performance of this strategy
      is evaluated using simulated and real high-performance liquid chromatography
      diode array detection (HPLC-DAD) datasets. The obtained results showed that the
      MCR-COW can efficiently correct elution time shifts of target compounds that are
      completely overlapped by coeluted interferences in complex chromatographic data.
      In addition, the PARAFAC analysis of aligned chromatographic data has the
      advantage of unique decomposition of overlapped chromatographic peaks to identify
      and quantify the target compounds in the presence of interferences. Finally, to
      confirm the reliability of the proposed strategy, the performance of the MCR-COW
      PARAFAC is compared with the frequently used methods of PARAFAC, COW-PARAFAC,
      multivariate curve resolution-alternating least squares (MCR-ALS), and MCR-COW
      MCR. In general, in most of the cases the MCR-COW-PARAFAC showed an improvement
      in terms of lack of fit (LOF), relative error (RE) and spectral correlation
      coefficients in comparison to the PARAFAC, COW-PARAFAC, MCR-ALS and MCR-COW-MCR
      results. 

PMID- 24580852
TI  - Determination of polyethylene glycol end group functionalities by combination of
      selective reactions and characterization by matrix assisted laser
      desorption/ionization time-of-flight mass spectrometry.
AB  - End groups play a critical role in macromolecular coupling reactions for building
      complex polymer architectures, yet their identity and purity can be difficult to
      ascertain using traditional analytical technique. Recent advances in mass
      spectrometry techniques have made matrix-assisted laser desorption/ionization
      time-of-fight (MALDI-TOF) mass spectrometry a rapid and powerful tool for
      providing detailed information about the identity and purity of homopolymer end
      groups. In this work, MALDI-TOF mass spectrometry was used to study end groups of
      linear polyethylene glycols. In particular, the identifications of alcohol, amine
      and thiol end groups are investigated because these nucleophilic moieties are
      among the most common within biological and synthetic macromolecules. Through
      comparative characterization of alcohol, amine, and thiol end groups, the exact
      identification of these end groups could be confirmed by selective and
      quantitative modification. The precision of this technique enables the
      unambiguous differentiation of primary amino groups relative to hydroxyl groups,
      which differ by only 1 mass unit. In addition, the quantitative conversion of
      various polyethylene glycol end groups using highly efficient coupling reactions
      such as the thiol-ene and azide-alkyne click reactions can be confirmed using
      MALDI-TOF mass spectrometry. 

PMID- 24580853
TI  - A surface-enhanced Raman scattering method for detection of trace glutathione on
      the basis of immobilized silver nanoparticles and crystal violet probe.
AB  - Unsatisfactory sensitivity and stability for molecules with low polarizability is
      still a problem limiting the practical applications of surface-enhanced Raman
      scattering (SERS) technique. By preparing immobilized silver nanoparticles
      (Fe3O4/Ag) through depositing silver on the surface of magnetite particles, a
      highly sensitive and selective SERS method for the detection of trace glutathione
      (GSH) was proposed on the basis of a system of Fe3O4/Ag nanoparticles and crystal
      violet (CV), in which the target GSH competed with the CV probe for the
      adsorption on the Fe3O4/Ag nanoparticles. Raman insensitive GSH replaced the
      highly Raman sensitive CV adsorbed on the surface of Fe3O4/Ag particles. This
      replacement led to a strong decrease of the CV SERS signal, which was used to
      determine the concentration of GSH. Under optimal conditions, a linear response
      was established between the intensity decrease of the CV SERS signal and the GSH
      concentration in the range of 50-700 nmol L(-1) with a detection limit of 40 nmol
      L(-1). The use of a Fe3O4/Ag substrate provided not only a great SERS enhancement
      but also a good stability, which guarantees the reproducibility of the proposed
      method. Its use for the determination of GSH in practical blood samples and cell
      extract yielded satisfactory results.

PMID- 24580854
TI  - Influence of metal loading and humic acid functional groups on the complexation
      behavior of trivalent lanthanides analyzed by CE-ICP-MS.
AB  - The complexation behavior of Aldrich humic acid (AHA) and a modified humic acid
      (AHA-PB) with blocked phenolic hydroxyl groups for trivalent lanthanides (Ln) is
      compared, and their influence on the mobility of Ln(III) in an aquifer is
      analyzed. As speciation technique, capillary electrophoresis (CE) was hyphenated
      with inductively coupled plasma mass spectrometry (ICP-MS). For metal loading
      experiments 25 mg L(-1) of AHA and different concentrations (cLn(Eu+Gd)=100-6000
      MUg L(-1)) of Eu(III) and Gd(III) in 10mM NaClO4 at pH 5 were applied. By CE-ICP
      MS, three Ln-fractions, assumed to be uncomplexed, weakly and strongly AHA
      complexed metal can be detected. For the used Ln/AHA-ratios conservative complex
      stability constants log betaLnAHA decrease from 6.33 (100 MUg L(-1) Ln(3+)) to
      4.31 (6000 MUg L(-1) Ln(3+)) with growing Ln-content. In order to verify the
      postulated weaker and stronger humic acid binding sites for trivalent Eu and Gd,
      a modified AHA with blocked functional groups was used. For these experiments 500
      MUg L(-1) Eu and 25 mg L(-1) AHA and AHA-PB in 10mM NaClO4 at pH-values ranging
      from 3 to 10 have been applied. With AHA-PB, where 84% of the phenolic OH-groups
      and 40% of the COOH-groups were blocked, Eu complexation was significantly lower,
      especially at the strong binding sites. The log beta-values decrease from 6.11
      (pH 10) to 5.61 at pH 3 (AHA) and for AHA-PB from 6.01 (pH 7) to 3.94 at pH 3. As
      a potential consequence, particularly humic acids with a high amount of strong
      binding sites (e.g. phenolic OH- and COOH-groups) can be responsible for a higher
      metal mobility in the aquifer due to the formation of dissolved negatively
      charged metal-humate species.

PMID- 24580855
TI  - Neuroactive steroids and the nervous system: further observations on an
      incomplete tricky puzzle.

PMID- 24580856
TI  - Bipolar II disorder in patients with a current diagnosis of recurrent depression.
AB  - OBJECTIVES: The prevalence of bipolar II disorder (BD-II) in Russia has never
      been studied. Therefore, we sought to identify patients meeting diagnostic
      criteria for BD-II among patients with a current diagnosis of recurrent
      depressive disorder (RDD) through the use of the Russian versions of the
      Hypomania Checklist (HCL-32) and Bipolarity Index scales for differentiating
      between BD-II and RDD. METHODS: In a non-interventional diagnostic study, we
      selected 409 patients aged between 18 and 65 years from two medical settings with
      (i) a current diagnosis of RDD, (ii) an illness duration of at least three years,
      and (iii) at least two affective episodes. The diagnosis was based on clinical
      assessment and confirmed by the Russian version of the Mini International
      Neuropsychiatric Interview. All patients were assessed by the HCL-32, the
      Bipolarity Index, and the Personal and Social Performance Scale. RESULTS: Among
      patients with a current diagnosis of RDD, 40.8% had a diagnosis of bipolar
      disorder (bipolar I disorder: 4.9%; BD-II: 35.9%). The average time lag from
      onset to a correct diagnosis of BD-II was 15 years and patients were treated only
      with antidepressants. The sensitivity of the Russian version of the HCL-32 at the
      optimal cutoff point (>=14.0) was 83.7%, and its specificity was 71.9%. The
      Bipolarity Index showed significant differences between the total scores of the
      patients with BD-II and RDD (31.8 versus 20.2; p < 0.0001). The optimal threshold
      was >=22.0 (sensitivity 73.5%; specificity 72.3%). CONCLUSIONS: In Russia,
      diagnostic errors are an important cause of the non-detection of bipolar
      disorder, particularly BD-II. The Russian version of the HCL-32 and the
      Bipolarity Index, as additional tools, could be useful for bipolarity screening.

PMID- 24580857
TI  - Metabolic labeling with stable isotope nitrogen (15N) to follow amino acid and
      protein turnover of three plastid proteins in Chlamydomonas reinhardtii.
AB  - BACKGROUND: The length of time that a protein remains available to perform its
      function is significantly influenced by its turnover rate. Knowing the turnover
      rate of proteins involved in different processes is important to determining how
      long a function might progress even when the stimulus has been removed and no
      further synthesis of the particular proteins occurs. In this article, we describe
      the use of 15N-metabolic labeling coupled to GC-MS to follow the turnover of free
      amino acids and LC-MS/MS to identify and LC-MS to follow the turnover of specific
      proteins in Chlamydomonas reinhardtii. RESULTS: To achieve the metabolic
      labeling, the growth medium was formulated with standard Tris acetate phosphate
      medium (TAP) in which14NH4Cl was replaced with 15NH415NO3 and (14NH4)6Mo7O24.4H2O
      was replaced with Na2MoO4.2H2O. This medium designated 15N-TAP allowed CC-125
      algal cells to grow normally. Mass isotopic distribution revealed successful 15N
      incorporation into 13 amino acids with approximately 98% labeling efficiency.
      Tryptic digestion of the 55 kDa SDS-PAGE bands from 14N- and 15N-labeled crude
      algal protein extracts followed by LC-MS/MS resulted in the identification of 27
      proteins. Of these, five displayed peptide sequence confidence levels greater
      than 95% and protein sequence coverage greater than 25%. These proteins were the
      RuBisCo large subunit, ATP synthase CF1 alpha and beta subunits, the
      mitochondrial protein (F1F0 ATP synthase) and the cytosolic protein (S-adenosyl
      homocysteine hydroxylase). These proteins were present in both labeled and
      unlabeled samples. Once the newly synthesized 15N-labeled free amino acids and
      proteins obtained maximum incorporation of the 15N-label, turnover rates were
      determined after transfer of cells into 14N-TAP medium. The t1/2 values were
      determined for the three plastid proteins (RuBisCo, ATP synthase CF1 alpha and
      beta) by following the reduction of the 15N-fractional abundance over time.
      CONCLUSION: We describe a more rapid and non-radioactive method to measure free
      amino acid and protein turnover. Our approach is applicable for determination of
      protein turnover for various proteins, which will lead to a better understanding
      of the relationship between protein lifetime and functionality.

PMID- 24580858
TI  - Personalized medicine: risk prediction, targeted therapies and mobile health
      technology.
AB  - Personalized medicine is increasingly being employed across many areas of
      clinical practice, as genes associated with specific diseases are discovered and
      targeted therapies are developed. Mobile apps are also beginning to be used in
      medicine with the aim of providing a personalized approach to disease management.
      In some areas of medicine, patient-tailored risk prediction and treatment are
      applied routinely in the clinic, whereas in other fields, more work is required
      to translate scientific advances into individualized treatment. In this forum
      article, we asked specialists in oncology, neurology, endocrinology and mobile
      health technology to discuss where we are in terms of personalized medicine, and
      address their visions for the future and the challenges that remain in their
      respective fields. 

PMID- 24580859
TI  - Sero-prevalence and risk factors of hepatitis B virus and human immunodeficiency
      virus infection among pregnant women in Bahir Dar city, Northwest Ethiopia: a
      cross sectional study.
AB  - BACKGROUND: Hepatitis B virus (HBV) and human immunodeficiency virus (HIV) are
      the two most important agents of infectious diseases. Both HBV and HIV share
      common modes of transmission and have serious effects on both pregnant women and
      infants. In Bahir Dar city administration, there is a scarcity of information on
      sero-prevalence of HIV and HBV infection among pregnant women. The main objective
      of this study was to assess sero-prevalence and risk factors of HIV and HBV
      infection among pregnant women attending antenatal care in Bahir Dar city,
      Northwest Ethiopia. METHODS: A cross-sectional study was conducted from March
      2013 to April 2013. Socio-demographic and explanatory variables were collected
      using a structured questionnaire by face to face interview. Hepatitis B surface
      antigen (HBsAg) was detected using an enzyme linked immunosorbent assay (ELISA).
      HIV infection was also detected using the national HIV test algorithms. The
      results were analyzed with descriptive statistics and binary logistic regression.
      The odds ratio and 95% Confidence intervals were calculated. RESULTS: A total of
      318 pregnant women with the mean age of 25.72 (SD. +/-5.14) years old were
      enrolled. Overall, 21/318 (6.6%) and 12 /318 (3.8%) of the pregnant women were
      positive for HIV and HBsAg, respectively. Of these, HIV/HBV co-infection rate was
      4 (19.0%). Previous history of blood transfusion (AOR = 3.7, 95% CI, 9.02-14.84),
      body tattooing (AOR = 5.7, 95% CI, 1.24-26.50), history of surgery (AOR = 11.1,
      95% CI, 2.64-46.88) and unsafe injection (AOR = 5.6, 95% CI, 1.44-22.19) were
      significantly associated with HBV infection. Previous history of piercing with
      sharp materials (AOR = 3.0, 95% CI 1.17-7.80) and history of abortion (AOR = 6.6,
      95% CI 2.50-17.71) were also statistically significant for HIV infection.
      CONCLUSIONS: This study indicates that HIV and HBV infections are important
      public health issues in our region that need to be addressed. All pregnant women
      need to be screened for both HIV and HBV infections during antenatal care.
      Furthermore, health education about modes of transmission of HIV and HBV has to
      be given.

PMID- 24580860
TI  - A multi-locus inference of the evolutionary diversification of extant flamingos
      (Phoenicopteridae).
AB  - BACKGROUND: Modern flamingos (Phoenicopteridae) occupy a highly specialized
      ecology unique among birds and represent a potentially powerful model system for
      informing the mechanisms by which a lineage of birds adapts and radiates.
      However, despite a rich fossil record and well-studied feeding morphology,
      molecular investigations of the evolutionary progression among modern flamingos
      have been limited. Here, using three mitochondrial (mtDNA) markers, we present
      the first DNA sequence-based study of population genetic variation in the widely
      distributed Chilean Flamingo and, using two mtDNA and 10 nuclear (nDNA) markers,
      recover the species tree and divergence time estimates for the six extant species
      of flamingos. Phylogenetic analyses include likelihood and Bayesian frameworks
      and account for potential gene tree discordance. Analyses of divergence times are
      fossil calibrated at the divergence of Mirandornithes (flamingos + grebes) and
      the divergence of crown grebes. RESULTS: mtDNA sequences confirmed the presence
      of a single metapopulation represented by two minimally varying mtDNA barcodes in
      Chilean flamingos. Likelihood and Bayesian methods recovered identical
      phylogenies with flamingos falling into shallow-keeled (comprising the Greater,
      American and Chilean Flamingos) and deep-keeled (comprising the Lesser, Andean
      and James's Flamingos) sub-clades. The initial divergence among flamingos
      occurred at or shortly after the Mio-Pliocene boundary (6-3 Ma) followed by quick
      consecutive divergences throughout the Plio-Pleistocene. There is significant
      incongruence between the ages recovered by the mtDNA and nDNA datasets, likely
      due to mutational saturation occurring in the mtDNA loci. CONCLUSION: The finding
      of a single metapopulation in the widespread Chilean Flamingo confirms similar
      findings in other widespread flamingo species. The robust species phylogeny is
      congruent with previous classifications of flamingos based on feeding morphology.
      Modern phoenicopterids likely originated in the New World with each sub-clade
      dispersing across the Atlantic at least once. Our divergence time estimates place
      flamingos among the youngest families of birds, counter to the classical notion
      of flamingos as among the oldest based on biogeography and the fossil record.
      Finally, we designate 'Phoeniconaias' as a junior synonym of 'Phoenicoparrus' and
      redefine the latter genus as containing all flamingos more closely related to
      Phoenicoparrus andinus than Phoenicopterus roseus.

PMID- 24580861
TI  - Tenting effect of the elevated sinus membrane over an implant with adjunctive use
      of a hydroxyapatite-powdered collagen membrane in rabbits.
AB  - PURPOSE: The aim of this study was to determine the de novo bone formation
      beneath the Schneiderian membrane supported by an implant and with the adjunctive
      use of a hydroxyapatite-powdered collagen (HAC) membrane without bone grafting in
      rabbit sinuses. MATERIAL AND METHODS: After sinus-floor elevation procedure, an
      experimentally devised mini-implant (4 mm in length and 3 mm in diameter) was
      placed in eight rabbits. For the experimental group, an HAC membrane was placed
      onto the elevated sinus mucosa prior to implant placement. The animals were
      allowed a healing period of either 4 or 8 weeks. Microcomputed tomography and
      histologic analyses were performed. RESULTS: All implants placed at the thin
      lateral bony wall were histologically osseointegrated. The topography of the
      newly formed bone appeared to slope gently from the medial side down to the
      lateral side. The volume of new bone was significantly greater in the
      experimental group than in the control group at 4 weeks (P < 0.05), but not at 8
      weeks. However, none of the samples in the two groups was entirely covered to the
      apex by bone tissue. CONCLUSIONS: It can be concluded that using the HAC membrane
      in combination with placement of an implant resulted in substantial bone
      formation around the implant, which might have been influenced by the proximity
      of the axial bony wall.

PMID- 24580863
TI  - [Mycology in dermatology].

PMID- 24580862
TI  - Ethnic disparities in acquiring 2009 pandemic H1N1 influenza: a case-control
      study.
AB  - BACKGROUND: Novel risk factors were associated with the 2009 pandemic A/H1N1
      virus (pH1N1). Ethnicity was among these risk factors. Ethnic disparities in
      hospitalization and death due to pH1N1 were noted. The purpose of this study is
      to determine whether there are ethnic disparities in acquiring the 2009 pandemic
      H1N1. METHODS: We conducted a test-negative case-control study of the risk of
      pH1N1 infection using data from Ontario, Canada. Cases were laboratory confirmed
      to have influenza using reverse-transcriptase polymerase chain reaction (RT-PCR),
      and controls were obtained from the same population and were RT-PCR negative.
      Multivariate logistic regression was used to determine the association between
      ethnicity and pH1N1 infection, while adjusting for demographic, clinical and
      ecological covariates. RESULTS: Adult cases were more likely than controls to be
      self-classified as East/Southeast Asian (OR = 2.59, 95% CI 1.02-6.57), South
      Asian (OR = 6.22, 95% CI 2.01-19.24) and Black (OR = 9.72, 95% CI 2.29-41.27).
      Pediatric cases were more likely to be self-identified as Black (OR = 6.43, 95%
      CI 1.83-22.59). However, pediatric cases without risk factors for severe
      influenza infection were more likely to be South Asian (OR 2.92, 95% CI 1.11
      7.68), Black (OR 16.02, 95% CI 2.85-89.92), and West Asian/Arab, Latin American
      or Multi-racial groups (OR 3.09 95% CI 1.06-9.00). CONCLUSIONS: pH1N1 cases were
      more likely to come from certain ethnic groups compared to test-negative
      controls. Insights into whether these disparities arise due to social or
      biological factors are needed in order to understand what approaches can be taken
      to reduce the burden of a future influenza pandemic.

PMID- 24580865
TI  - Wolfram Sterry: Physician - scientist - cosmopolitan.

PMID- 24580867
TI  - Wolfram Sterry - a unique visionary medical leader.

PMID- 24580868
TI  - Wolfram Sterry: Exceptional individual and dermatologist with vision.

PMID- 24580870
TI  - Wolfram Sterry: Writer and editor.

PMID- 24580874
TI  - Macrophages - sensors and effectors coordinating skin damage and repair.
AB  - Restoration of skin integrity and homeostasis following injury is a vital
      process. Wound healing disorders, including chronic skin ulcers and pathological
      scarring, are of major clinical impact. The current therapeutic approaches are
      often not sufficient. The development of novel efficient therapies requires a
      thorough understanding of the underlying molecular mechanisms. A cardinal feature
      of non-healing skin ulcers and excessive scarring is a prolonged inflammatory
      response at the wound site, which aborts the healing response. Modulation of the
      local immune response may be an effective therapeutic strategy to correct
      impaired healing conditions. Yet, the specific mechanisms of inflammation,
      particularly the role of the diverse leukocyte lineages attracted to the site of
      tissue damage, have not been resolved. Recent findings in diverse experimental
      model systems and clinical studies have refined the understanding of
      monocyte/macrophage biology and the role of cells of the monocytic lineage in
      tissue regeneration. Thus, monocytes/macrophages are emerging as novel and
      interesting therapeutic targets to interfere in wound healing pathologies. In
      this article we will review the role of monocytes/macrophages in skin repair in
      the light of the recent literature and findings from our own group. This article
      will provide a rationale for monocyte/macrophage-based therapies to facilitate
      the healing response. 

PMID- 24580875
TI  - Angiolymphoid hyperplasia with eosinophilia and Kimura's disease - a clinical and
      histopathological comparison.
AB  - Angiolymphoid hyperplasia with eosinophilia (ALHE) is a benign vascular neoplasm
      mainly affecting middle-aged women. Lesions typically affect the head and neck
      region. ALHE is considered a distinct disease entity different from Kimura's
      disease, a benign reactive lymphoid proliferation that is predominantly seen in
      young Asian men although it can affect all ethnic groups. In contrast to ALHE,
      Kimura's disease is typically associated with peripheral blood eosinophilia,
      increased serum IgE and lymphadenopathy. Several case reports suggest an overlap
      between ALHE and Kimura's disease. We review the current literature and discuss
      whether AHLE and Kimura's disease might represent two extreme variants of the
      same disease entity.

PMID- 24580878
TI  - Risk stratification of systemic allergic reactions during Hymenoptera venom
      immunotherapy buildup phase.
AB  - BACKGROUND: Comparability of previous studies assessing the incidence of systemic
      reactions during Hymenoptera venom immunotherapy (VIT) is impaired by methodical
      differences concerning the definition and classification of VIT-induced
      anaphylaxis. Our study aims to systematically evaluate the time course and
      clinical symptoms of VIT-related systemic reactions. PATIENTS AND METHODS: 12
      year data on 818 buildup cycles including 8,504 single injections were retrieved
      from detailed inpatient treatment protocols. The severity of VIT-related
      anaphylaxis was graded according to a system proposed by the World Allergy
      Organization in 2010. RESULTS: Objective allergic reactions occurred in 28 (3.4
      %) buildup cycles; treatment with antihistamines and/or corticosteroids was
      invariably effective. 23 exclusively cutaneous reactions occurred after a median
      time interval of 60 minutes (5-480 min.) following the last injection. 0.6 % of
      the buildup cycles were complicated by moderate to severe anaphylaxis, which
      occurred more rapidly than mere urticaria and predominantly during honeybee VIT.
      Patients with moderate to severe anaphylaxis more frequently reported severe
      index sting reactions and had higher baseline serum tryptase concentrations.
      CONCLUSIONS: Objective allergic reactions during VIT are rare, and severe
      anaphylaxis is extremely rare. The use of a consistent classification system for
      VIT-induced systemic reactions is required to identify risk factors not only for
      their general incidence, but also for the exceptionally severe anaphylactic
      reactions.

PMID- 24580881
TI  - Vegetating foot ulcer as presenting sign of acquired immunodeficiency syndrome.

PMID- 24580886
TI  - Neonatal infections: group B streptococcus.
AB  - INTRODUCTION: One in four women carry group B streptococci vaginally, which can
      infect the amniotic fluid before delivery or can infect the baby during delivery,
      causing sepsis, pneumonia, or meningitis. Very low-birthweight infants are at
      much higher risk of infection or mortality, with up to 3% infected and mortality
      rates of up to 30%, even with immediate antibiotic treatment. Late-onset group B
      streptococcal infection begins from 7 days of age, and usually causes fever or
      meningitis, but is less often fatal compared with early infection. METHODS AND
      OUTCOMES: We conducted a systematic review and aimed to answer the following
      clinical question: what are the effects of prophylactic treatment of asymptomatic
      neonates less than 7 days old with known risk factors for early-onset group B
      streptococcal infection? We searched: Medline, Embase, The Cochrane Library, and
      other important databases up to November 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 5 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:
      different antibiotics, monitoring and selective treatment, and routine antibiotic
      prophylaxis.

PMID- 24580887
TI  - Higher proportion of G2P[4] rotaviruses in vaccinated hospitalized cases compared
      with unvaccinated hospitalized cases, despite high vaccine effectiveness against
      heterotypic G2P[4] rotaviruses.
AB  - The overall vaccine effectiveness of the monovalent rotavirus vaccine in an
      observational, prospective, multicentre, hospital-based case-control study in
      Belgium (RotaBel) was 90%. However, rotavirus genotype and co-infecting pathogens
      are important parameters to take into account when assessing vaccine
      effectiveness. In this study we specifically investigated the effect of rotavirus
      genotypes and co-infecting pathogens on vaccine effectiveness of the monovalent
      vaccine. In addition, we also investigated the effect of co-infecting pathogens
      on disease severity. From February 2008 to June 2010 stool samples of rotavirus
      gastroenteritis cases of a random sample of 39 Belgian hospitals were collected
      and subsequently genotyped. Fisher's exact tests were performed to investigate
      the relationships between rotavirus genotype, co-infecting pathogens and disease
      severity. The vaccine effectiveness of a full series of the monovalent rotavirus
      vaccine against hospitalized rotavirus gastroenteritis caused by G1P[8] rotavirus
      strains was 95% (95% CI 77.5-98.7). Against G2P[4], the vaccine effectiveness was
      85% (95% CI: 63.7-93.8). G4P[8]- and G3P[8]-specific vaccine effectiveness was
      90% (95% CI 19.2-98.7) and 87% (95% CI -5.2 to 98.4), respectively. A post-hoc
      analysis showed that the genotype distribution was significantly related to the
      vaccination status (p <0.001), whereby G2P[4] strains were proportionally more
      prevalent in vaccinated cases than in unvaccinated cases. No statistical
      associations were found between co-infection status and vaccination status,
      Vesikari severity score or rotavirus genotype. The high vaccine effectiveness
      against the individual genotypes implies robust protection of the monovalent
      rotavirus vaccine against hospitalized rotavirus gastroenteritis caused by the
      major human rotavirus genotypes. The prevalence of G2P[4] requires continued
      monitoring.

PMID- 24580890
TI  - Harnessing lipid absorption pathways to target the lymphatic system.

PMID- 24580888
TI  - HIV-associated neurocognitive disorder in HIV-infected Koreans: the Korean
      NeuroAIDS Project.
AB  - OBJECTIVES: HIV-associated neurocognitive disorder (HAND) is an independent
      predictor of early mortality and is associated with many difficulties in
      activities of daily living. We sought to determine the prevalence of and risk
      factors for HAND in HIV-infected Koreans. In addition, we investigated the
      performance of screening tools and components of neuropsychological (NP) tests
      for diagnosing HAND. METHODS: HIV-infected patients were enrolled consecutively
      from two different urban teaching hospitals in Seoul, South Korea between March
      2012 and September 2012. Participants completed a detailed NP assessment of six
      cognitive domains commonly affected by HIV. The Frascati criteria were used for
      diagnosing HAND. Four key questions, the International HIV Dementia Scale (IHDS)
      and Montreal Cognitive Assessment (MoCA)-K were also assessed as potential tools
      for screening for HAND. RESULTS: Among the 194 participants, the prevalence of
      HAND was 26.3%. Asymptomatic neurocognitive impairment and minor neurocognitive
      disorder accounted for 52.9 and 47.1% of the patients with HAND, respectively. In
      multivariate analysis, haemoglobin (Hb) level <= 13 g/dL (P = 0.046) and current
      use of a protease inhibitor-based regimen (P = 0.031) were independent risk
      factors for HAND. The sensitivity and specificity of the IHDS were 72.6 and
      60.8%, and those of MoCA-K were 52.9 and 73.4%, respectively. The IHDS (P <
      0.001) and MoCA-K (P < 0.001) were both useful for screening for HAND. Among NP
      tests, the sensitivity and specificity of the Grooved Pegboard Test were 90.2 and
      72.0%, and those of the Wisconsin Card Sorting Test were 61.2 and 84.4%,
      respectively. CONCLUSIONS: HAND is a prevalent comorbidity in HIV-infected
      Koreans. Active screening and diagnosis with effective tools, such as the IHDS,
      MoCA-K and Grooved Pegboard Test, could be used to identify this important
      complication.

PMID- 24580889
TI  - The attitudes of mental health professionals towards patients' desire for
      children.
AB  - BACKGROUND: When a patient with a serious mental illness expresses a desire for
      children, mental health professionals are faced with an ethical dilemma. To date,
      little research has been conducted into their strategies for dealing with these
      issues. METHODS: Seven focus groups with a total of 49 participants from all
      professional groups active in mental health (nurses, psychologists, social
      workers and psychiatrists) were conducted in a 330-bed psychiatric hospital.
      Group discussions were transcribed verbatim and analysed by the documentary
      method described by Bohnsack. RESULTS: Mental health professionals did not feel
      that their patients' desire for children was as important in daily practice as
      were parenting issues. When discussing the desire for children on the part of
      patients, the following themes emerged: "the patient's own decision",
      "neutrality", "the patient's well-being", "issues affecting the children of
      mentally ill parents" and "appropriate parenthood". In order to cope with what
      they perceived as conflicting norms, mental health professionals developed the
      following (discursive) strategies: "subordination of child welfare", "de
      professionalisation", "giving rational advice" and "resignation". CONCLUSIONS:
      The theme of "reproductive autonomy" dominated mental health professionals'
      discourse on the desire for children among psychiatric patients. "Reproductive
      autonomy" stood in conflict with another important theme (patient's children).
      Treating reproductive issues as taboo is the result of the gap between MHPs'
      perceptions of (conflicting) norms when dealing with a patient's desire for
      children and the limited opportunities to cope with them appropriately.In order
      to support both patients with a desire for children and mental health
      professionals who are charged with providing counselling for such patients, there
      is a need to encourage ethical reflection and to focus on clinical
      recommendations in this important area.

PMID- 24580891
TI  - Hierarchically structured ZnO nanorods-nanosheets for improved quantum-dot
      sensitized solar cells.
AB  - ZnO nanorods (NRs) and nanosheets (NSs) were fabricated by adjusting the growth
      orientation of ZnO crystals in the reaction solution, respectively. The thin ZnO
      NSs were slowly assembled on the surface of NRs to form a hierarchically
      structured NR-NS photoelectrode for constructing CdS/CdSe quantum-dot-sensitized
      solar cells (QDSCs). This hierarchical structure had two advantages in improving
      the power conversion efficiency (PCE) of the solar cells: (a) it increased the
      surface area and modified the surface profile of the ZnO NRs to aid in harvesting
      more quantum dots, which leads to a high short-current density (Jsc); (b) it
      facilitated transportation of the electrons in this compact structure to reduce
      the charge recombination, which led to enhancement of the open-circuit voltage
      (Voc) and fill factor (FF). As a result, the QDSC assembled with the hierarchical
      NR-NS photoelectrode exhibited a high PCE of 3.28%, which is twice as much as
      that of the NR photoelectrode (1.37%). 

PMID- 24580892
TI  - Unusual trichobezoar of the stomach and the intestine: a case report.
AB  - INTRODUCTION: Trichobezoars are an infrequent form of bezoar found in the stomach
      or intestine, created from ingested hair. This condition has been well described
      in the surgical literature, but less reported in psychiatry. CASE PRESENTATION:
      We describe the case of an 18-year-old Middle Eastern Caucasian woman with
      trichotillomania who presented to our emergency department with a history of
      central abdominal pain associated with vomiting and constipation for five days.
      An examination showed a trichobezoar requiring emergent surgical intervention,
      and indicating the need for psychiatric treatment. The trichobezoar was treated
      successfully by laparotomy. CONCLUSION: The medical and psychiatric sequelae of
      trichotillomania should not be underestimated, and early diagnosis and treatment
      is of utmost importance to save the patient's life and prevent recurrence.
      Although laparotomy is still considered an excellent option, pharmacotherapy and
      behavioral assessment play a useful role in patient management. Our case
      highlights the fundamental concept of a holistic approach rather than only
      treating the symptoms, by considering factors such as genetic influences to
      understand the disease.

PMID- 24580893
TI  - Feasibility of and rectal dosimetry improvement with the use of SpaceOAR(r)
      hydrogel for dose-escalated prostate cancer radiotherapy.
AB  - INTRODUCTION: The aim of this study was to investigate the feasibility of
      injecting a temporary spacer between the rectum and the prostate and to quantify
      the degree of rectal dosimetric improvement that might result. METHODS: Ten
      patients underwent CT and MRI before and after injection of 10 cc of hydrogel and
      at completion of radiotherapy. Hydrogel was injected under general anaesthetic
      using a transperineal approach. The primary endpoints were perioperative toxicity
      and rectal dosimetry (V80, V75, V70, V65, V40 and V30). Secondary endpoints were
      acute gastrointestinal toxicity during and 3 months following radiotherapy and
      the stability of the hydrogel. Treatment for all patients was planned
      incorporating volumetric modulated arc therapy with a D95 of 80 Gy in 40
      fractions to the prostate and proximal seminal vesicles on both the pre- and post
      hydrogel scans. Toxicity was scored with the Common Terminology Criteria, v. 3.0.
      RESULTS: In the first 24 h, two patients described an increase in bowel movement
      frequency. The comparison plans had identical prescription doses. Rectal doses
      were significantly lower for all hydrogel patients for all dose endpoints (V80 =
      7% vs. 0.1%, V75 = 10.3% vs. 1.1%, V70 = 13.2% vs. 2.7%, V65 = 15.8% vs. 4.6%,
      V40 = 35.2% vs. 23.3%, V30 = 52.6% vs. 38.5%; P < 0.001). Post-treatment MRI
      showed gel stability. Grade 1 bowel toxicity was reported in six patients during
      radiotherapy and two patients at 3 months' follow-up. No Grade 2 or Grade 3 acute
      bowel toxicity was reported. CONCLUSION: SpaceOAR hydrogel was successfully
      injected in 10 patients with minimal side effects. Rectal dosimetry was
      significantly improved in all patients. This study has been extended to 30
      patients with longer follow-up planned.

PMID- 24580894
TI  - Telomeric transcriptome from Chironomus riparius (Diptera), a species with
      noncanonical telomeres.
AB  - Although there are alternative telomere structures, most telomeres contain DNA
      arrays of short repeats (6-26 bp) maintained by telomerase. Like other diptera,
      Chironomus riparius has noncanonical telomeres and three subfamilies, TsA, TsB
      and TsC, of longer sequences (176 bp) are found at their chromosomal ends.
      Reverse transcription PCR was used to show that different RNAs are transcribed
      from these sequences. Only one strand from TsA sequences seems to render a
      noncoding RNA (named CriTER-A); transcripts from both TsB strands were found
      (CriTER-B and alphaCriTER-B) but no TsC transcripts were detected. Interestingly,
      these sequences showed a differential transcriptional response upon heat shock,
      and they were also differentially affected by inhibitors of RNA polymerase II and
      RNA polymerase III. A computer search for transcription factor binding sites
      revealed putative regulatory cis-elements within the transcribed sequence,
      reinforcing the experimental evidence which suggests that the telomeric repeat
      might function as a promoter. This work describes the telomeric transcriptome of
      an insect with non-telomerase telomeres, confirming the evolutionary conservation
      of telomere transcription. Our data reveal differences in the regulation of
      telomeric transcripts between control and stressful environmental conditions,
      supporting the idea that telomeric RNAs could have a relevant role in cellular
      metabolism in insect cells. 

PMID- 24580895
TI  - The looking to the future medical student program: recruiting tomorrow's leaders.

PMID- 24580896
TI  - Disciplined practice and improving clinical and pathologic staging for non-small
      cell lung cancer.

PMID- 24580897
TI  - Revisiting surrogate consent for ventricular assist device placement.

PMID- 24580898
TI  - Invited commentary.

PMID- 24580899
TI  - Invited commentary.

PMID- 24580900
TI  - Invited commentary.

PMID- 24580901
TI  - Invited commentary.

PMID- 24580902
TI  - Invited commentary.

PMID- 24580903
TI  - Invited commentary.

PMID- 24580904
TI  - Invited commentary.

PMID- 24580905
TI  - Invited commentary.

PMID- 24580906
TI  - Invited commentary.

PMID- 24580907
TI  - Invited commentary.

PMID- 24580908
TI  - Invited commentary.

PMID- 24580909
TI  - Invited commentary.

PMID- 24580910
TI  - Invited commentary.

PMID- 24580911
TI  - Invited commentary.

PMID- 24580912
TI  - Invited commentary.

PMID- 24580913
TI  - Invited commentary.

PMID- 24580914
TI  - Invited commentary.

PMID- 24580915
TI  - Invited commentary.

PMID- 24580916
TI  - Invited commentary.

PMID- 24580917
TI  - Invited commentary.

PMID- 24580918
TI  - Cardiac tamponade: new technology masking an old nemesis.
AB  - A 16-year-old male patient underwent bilateral pulmonary embolectomy complicated
      by reperfusion injury and acute respiratory distress syndrome requiring
      venovenous extracorporeal membrane oxygenation support using a bicaval double
      lumen catheter. A unique hemodynamic profile developed consistent with tamponade
      but without an associated decrease in venovenous extracorporeal membrane
      oxygenation pump flow, improved venovenous extracorporeal membrane oxygenation
      circuit preload, and decreased recirculation. The use of newer bicaval double
      lumen catheters can result in old problems presenting in new ways and require
      clinicians to be ever vigilant. 

PMID- 24580919
TI  - Extensive tricuspid valve repair after endocarditis using CorMatrix extracellular
      matrix.
AB  - Surgical repair of tricuspid regurgitation after medical management of infective
      endocarditis can present a challenging scenario. We present the case of a 53-year
      old man in whom a conventional tricuspid valve operation was deemed suboptimal.
      Instead, we used a commercially available extracellular matrix (ECM) to perform
      an extensive reconstruction of his tricuspid valve. Follow-up shows dramatic
      symptomatic resolution and reverse remodeling of his dilated right ventricle. 

PMID- 24580920
TI  - Simultaneous repair of multiple aortic aneurysms: be courageous in minimally
      invasive era.
AB  - The simultaneous treatment of multiple ruptured aortic aneurysms is a surgical
      challenge. Here we present a case of a 53-year-old woman with Marfan syndrome who
      had annuloaortic ectasia of 4.2 cm and a thoracoabdominal aortic aneurysm of 6
      cm. The patient developed acute aortic dissection complicated with cardiac
      tamponade and thoracoabdominal aortic rupture. An emergency operation, which
      included a Bentall operation, total arch replacement, and thoracoabdominal
      repair, was performed for 2 remote aneurysms. By paying particular attention to
      organ perfusion, a single-stage operation was successfully performed and the
      patient fully recovered.

PMID- 24580921
TI  - Calcified amorphous tumor of the left ventricular outflow tract.
AB  - We report a very rare case of a calcified amorphous tumor presenting atypically
      as a mobile left ventricular outflow tract mass in a 69-year-old female who was
      admitted for shortness of breath. 

PMID- 24580922
TI  - Modified Nikaidoh procedure with double-root translocation in a 1-year-old boy.
AB  - A 1-year-old boy weighing 10.4 kg underwent successful biventricular repair for
      transposition of the great arteries, a ventricular septal defect, and a left
      ventricular outflow tract (LVOT) obstruction with moderate pulmonary stenosis of
      the bicuspid pulmonary valve (z score of -4.4 for the pulmonary valve) by means
      of a modified Nikaidoh procedure with double root translocation by use of a valve
      spared pulmonary root. The postoperative echocardiogram showed no LVOT
      obstruction, no aortic valve regurgitation, and mild pulmonary stenosis and
      pulmonary valve regurgitation. No reintervention has been required during the 6
      year follow-up, with annular growth of the pulmonary valve. 

PMID- 24580923
TI  - Slide tracheoplasty with concomitant aortic arch repair in a low-weight neonate.
AB  - We report the successful surgical management of a hypoplastic aortic arch, severe
      tracheal stenosis, and acute respiratory failure in a low-birth-weight neonate.
      The technical details that facilitated concomitant slide tracheoplasty and aortic
      arch reconstruction are discussed. 

PMID- 24580924
TI  - Repair of an unusual aortic coarctation using an extracellular matrix patch.
AB  - The surgical treatment of neonatal aortic coarctation is usually accomplished
      with a termino-terminal anastomosis or a subclavian flap. The use of a patch to
      enlarge the isthmal narrowing may be an alternative but is frequently complicated
      by aneurysmal dilatation on the aortic wall opposite to the patch, probably
      because it disrupts the vascular anatomic integrity. Extracellular matrix patches
      promise to restore the original tissue structure and could therefore be a valid
      alternative to other materials. We describe an aortic coarctation with an
      uncommon anatomic aspect treated with a CorMatrix (CorMatrix, Alpharetta, GA)
      extracellular matrix patch. 

PMID- 24580925
TI  - Unroofing intramural coronary artery for late coronary events after arterial
      switch operation.
AB  - The incidence of intramural coronary arteries in patients with transposition of
      the great arteries is relatively rare. Intramural coronary arteries are highly
      associated with early and late coronary adverse events. We report a case of late
      coronary events caused by an intramural left coronary artery, which was
      successfully treated by the unroofing procedure. 

PMID- 24580926
TI  - Mitral commissural repair with autologous fresh pericardium in an infant.
AB  - We describe the successful mitral valve repair with autologous fresh pericardium
      in a 5-month-old infant with acute progressive mitral regurgitation. The
      intraoperative findings consisted of fragile mitral valve leaflets with multiple
      chordal rupture of both the anterior and posterior leaflets. The disrupted
      anterolateral commissure was reconstructed using autologous fresh pericardium, a
      technique not previously reported in an infant of this size. Follow-up
      echocardiography for up to 7 years showed only trivial mitral regurgitation and
      no mitral stenosis. 

PMID- 24580928
TI  - Recurrent laryngeal nerve paralysis by compression from a tracheal diverticulum.
AB  - Tracheal diverticulum is a rarely encountered entity, located usually on the
      right side of the trachea as an outpouching of the wall. Based on mainly
      histologic features, it can be classified in a congenital or an acquired form. It
      is usually an incidental finding in an asymptomatic patient. When symptoms are
      present, they are mostly nonspecific such as chronic cough, dyspnea, or pulmonary
      infections. We describe a case of dysphonia due to right recurrent laryngeal
      nerve compression from a tracheal diverticulum. Computed tomography scanning and
      bronchoscopy revealed the lesion and surgical resection resolved the symptom. 

PMID- 24580927
TI  - Innominate pseudoaneurysm subtotally compressing the trachea as a result of blunt
      trauma.
AB  - Blunt traumatic innominate pseudoaneurysm is rare, and coexisting airway distress
      is even rarer. We describe a case of innominate pseudoaneurysm that subtotally
      compressed the trachea in a 45-year-old man. The patient also had bovine-type
      arch anatomy. He experienced exacerbated respiratory distress on anesthesia
      induction. A cardiopulmonary bypass (CPB) circuit was immediately established
      through the femoral vessels. The aortic arch was replaced with a branched graft
      under circulatory arrest and antegrade cerebral perfusion. The pseudoaneurysm was
      eliminated and airway compression was completely relieved. The patient fully
      recovered without major complications. The unique feature of this case is its
      association with airway compression, which is uncommon but potentially lethal. 

PMID- 24580929
TI  - Successful management of anastomotic leakage and lung fistula after
      esophagectomy.
AB  - We report the successful management of a case of anastomotic leakage with a lung
      fistula as a complication of esophagectomy by use of a double elementary diet
      tube. 

PMID- 24580930
TI  - Extracorporeal membrane oxygenation support after Ivor-Lewis esophagectomy for
      esophageal adenocarcinoma.
AB  - Respiratory failure after Ivor-Lewis esophagectomy results in poor outcomes.
      Limited treatment strategies are available to manage this severe complication.
      One possibility is extracorporeal support. We report the successful use of
      extracorporeal support as a successful strategy for refractory respiratory
      failure. 

PMID- 24580931
TI  - Collision tumor of esophagus: report of three cases.
AB  - Collision tumors are rare, and they are not well-recognized entities. Collision
      tumors of the esophagus are rarer. Here we report 3 patients with esophageal
      collision tumors and discuss their characteristics. 

PMID- 24580932
TI  - Asymptomatic but functional paraganglioma of the posterior mediastinum.
AB  - A 72-year-old woman was referred to our hospital because of a posterior
      mediastinal tumor. On the basis of detailed imaging tests, including (123)I
      metaiodobenzylguanidine single photon emission computed tomography-computed
      tomography, and elevated values of catecholamines in the plasma and urine, the
      tumor was diagnosed as a functional mediastinal paraganglioma even in the absence
      of symptoms. After preoperative blood pressure control, surgical resection was
      performed. During the operation, the systemic blood pressure increased
      transiently as a result of surgical manipulation of the tumor. Soon after the
      tumor was removed, the patient conversely experienced hypotension. The
      postoperative course was uneventful, and pathologic diagnosis revealed a
      paraganglioma. 

PMID- 24580933
TI  - Percutaneous closure of a traumatic ventricular septal defect after transcatheter
      aortic valve implantation.

PMID- 24580934
TI  - A giant left coronary sinus of valsalva aneurysm after type A aortic dissection.

PMID- 24580936
TI  - Local cardiac recurrence of intravenous leiomyomatosis.

PMID- 24580935
TI  - A rare anatomic variant: partial anomalous pulmonary venous connection of the
      right pulmonary veins to an aneurysmal left vertical vein.

PMID- 24580937
TI  - Orthotopic heart transplantation in patients with persistent left superior vena
      cava: bicaval and biatrial techniques.
AB  - Persistent left superior vena cava (LSVC) is the most common congenital venous
      abnormality. With the increasing number of children who survive into adulthood
      with congenital heart malformations, the recognition of persistent LSVC among
      patients with advanced heart failure is likely to rise. We present two cases of
      orthotopic heart transplantation in the setting of LSVC successfully managed with
      biatrial and bicaval techniques. 

PMID- 24580938
TI  - Electric suction-lavage device for video-assisted thoracoscopic surgery treatment
      of empyema and hemothorax.
AB  - We describe the use of an electric trigger-controlled suction-lavage device for
      the evacuation of empyema or clotted hemothorax. Wound debridement systems
      provide efficient irrigation and debris removal. It is frequently used for
      orthopedic procedures or infected wound rinsing. Internet search of the
      literature did not result in any paper describing the use of this technique for
      thoracic surgery. We present our experience with an electrical wound-washing
      device in video-assisted thoracoscopic surgery for thoracic empyema or clotted
      hemothorax. 

PMID- 24580939
TI  - Herbert Sloan, MD, October 10, 1914 - May 17, 2013.
AB  - Dr Herbert Sloan was the 10th president of The Society of Thoracic Surgeons and
      served for 15 years as the second editor of The Annals of Thoracic Surgery. One
      of few thoracic surgeons to lead both organizations, he also served as the 60th
      president of the American Association for Thoracic Surgery. Deeply committed to
      the mission of the American Board of Thoracic Surgery to maintain the highest
      standards for our specialty, he served on the American Board of Thoracic Surgery
      for 20 years, 13 as its secretary-treasurer. He left a legacy of thoracic surgery
      resident education as head of the Section of Thoracic Surgery at the University
      of Michigan.

PMID- 24580940
TI  - Reply: To PMID 23816417.

PMID- 24580941
TI  - Transcatheter aortic valve implantation versus surgical aortic valve replacement.

PMID- 24580942
TI  - Therapeutic options against internal thoracic artery spasm.

PMID- 24580943
TI  - Reply: To PMID 23352419.

PMID- 24580944
TI  - Should we prone cardiac surgery patients with acute respiratory distress
      syndrome?

PMID- 24580945
TI  - Reply: To PMID 23773733.

PMID- 24580946
TI  - Evidence of normalized cardiopulmonary function after pectus excavatum repair.

PMID- 24580947
TI  - Reply: To PMID 23915590.

PMID- 24580948
TI  - Early pediatric renal replacement therapy: is the baby wash actually killing the
      baby?

PMID- 24580949
TI  - The role of video-assisted thoracic surgery lobectomy in unexpected N2 cases.

PMID- 24580950
TI  - Patch repair of anomalous origin of the left main coronary artery from the
      anterior aortic sinus.
AB  - Anomalous origin of the left main coronary artery from the anterior aortic sinus
      is a rare but potentially lethal congenital disease. We report two adolescent
      patients with this anomaly who underwent surgical plasty using a saphenous vein
      patch, rather than unroofing or fenestration technique, as was typically done.
      This report suggests that surgical angioplasty can be performed safely and
      effectively to treat this anomaly. 

PMID- 24580951
TI  - Occlusion of the left main coronary artery os by a tethered aortic valve cusp.
AB  - We report a 4-month-old girl who presented with poor ventricular function and was
      found to have occlusion of the left main coronary artery os by a tethered aortic
      cusp. The patient underwent surgical delamination of the aortic valve leaflet,
      revealing a normal left coronary os. After operative repair, her left ventricular
      function improved significantly. This diagnosis should be included in the
      differential in all children presenting with cardiac dysfunction. 

PMID- 24580952
TI  - Repair of a duplicate mitral valve in a patient with ascending aortic aneurysm
      and bicuspid aortic valve.
AB  - We present the case of a 48-year-old man presenting to the emergency department
      with acute onset of chest pain radiating to the back in the setting of a known
      ascending aortic aneurysm. Preoperative echocardiography revealed an incompetent
      duplicate mitral valve, with a medially directed eccentric 3+ jet of mitral
      regurgitation, and a bicuspid aortic valve. The patient was scheduled for aortic
      root and valve replacement with concurrent mitral valve repair. Intraoperative
      examination revealed an incompetent duplicate mitral valve separated from the
      physiologic mitral valve by a band of interatrial tissue. Successful repair was
      undertaken by oversewing the mitral valve. Postoperative echocardiography allowed
      for evaluation of this unique repair, which revealed no evidence of further
      mitral regurgitation and confirmed a successful repair of the mitral
      regurgitation without any need for an implantable device. Our goal is that this
      case and its positive treatment outcome, along with our three-dimensional
      echocardiographic images correlated with the intraoperative findings and
      photographs, will further the understanding of the diagnosis and treatment of
      this rare condition. 

PMID- 24580953
TI  - Constrictive pericarditis caused by immunoglobulin G4-related disease.
AB  - An 81-year-old man with congestive heart failure was admitted to our hospital.
      Computed tomography of the chest revealed pericardial thickening without
      calcification. Ultrasonic echocardiography and cardiac magnetic resonance imaging
      demonstrated diastolic dysfunction. Cardiac catheterization showed bilateral
      elevation of ventricular end-diastolic pressure with a square root sign. The
      preoperative serum immunoglobulin G4 (IgG4) level was abnormally high.
      Pericardiectomy and pericardiotomy were considered to be indicated and were
      performed. Histopathologic examination revealed tissue infiltration by IgG4
      positive plasma cells, and constrictive pericarditis caused by IgG4-related
      disease was diagnosed. Postoperatively, the patient received additional
      corticosteroid therapy. The latest cardiac magnetic resonance image showed
      further improvement in diastolic function. 

PMID- 24580954
TI  - Primary cardiac paraganglioma with intratumoral coronary artery aneurysm.
AB  - We report here the surgical treatment of a rare case of primary cardiac
      paraganglioma with an intratumoral coronary artery aneurysm. 

PMID- 24580955
TI  - A pitfall during endobronchial ultrasound-guided transbronchial forceps biopsy of
      the mediastinal lymph nodes.
AB  - The high diagnostic yield and favorable safety profile of endobronchial
      ultrasound-guided transbronchial forceps biopsy of the mediastinal lymph nodes
      have been recently demonstrated. We report an unusual technical problem during
      endobronchial ultrasound-guided transbronchial forceps biopsy that could be a
      prerequisite for severe complications. A rupture of the steering band precluded
      closure of the forceps jaws opened in the subcarinal lymph node. A solution to
      the problem is presented, together with other procedure-related complications
      reported in the literature. The report emphasizes that a dysfunction of the
      forceps steering band can result in severe complications when it occurs during
      transbronchial sampling of mediastinal lesions. 

PMID- 24580956
TI  - Transhiatal laparoscopic resection of intrathoracic esophageal duplication in a 6
      month-old boy.
AB  - We report the case of a 6-month-old boy known antenatally to have a mediastinal
      cyst. Postnatal workup showed a noncommunicating compressive cyst bound to the
      lower third of the native esophagus. He underwent its removal by transhiatal
      laparoscopy. This appears to be the first case of laparoscopic removal of a
      thoracic esophageal duplication cyst in a child. 

PMID- 24580957
TI  - Arrow wound to the heart.

PMID- 24580958
TI  - Tetralogy with pulmonary atresia and leaking left pulmonary artery aneurysm.

PMID- 24580959
TI  - Single-incision thoracoscopic surgery using an anchoring suture of the lung
      parenchyma for two-directional traction.
AB  - Single-incision thoracoscopic surgery (SITS) is difficult to perform because of
      an increased likelihood of collision between surgical instruments; moreover, the
      use of all the instruments through a single incision requires the creation of a
      relatively large incision. Therefore, a new SITS technique needs to be developed
      to reduce the likelihood of collision between surgical instruments and the
      incision size to a cosmetically acceptable one. In the present study, we aimed to
      perform SITS to easily avoid collisions between instruments through small
      incision sites by means of a novel two-directional traction method using
      anchoring lung sutures. 

PMID- 24580960
TI  - Frailty and quality of life: a cross-sectional study of Brazilian patients with
      pre-dialysis chronic kidney disease.
AB  - PURPOSE: Chronic kidney disease (CKD) induces frailty and worsens quality of life
      (QOL), even in the early stages of the disease and in young patients. However,
      there is a lack of knowledge about the relationship between frailty and QOL in
      CKD patients. Thus, we investigated this relationship in a sample of CKD
      patients. METHODS: A cross-observational study was conducted, in which 61 CKD
      patients receiving pre-dialysis treatment were assessed. All participants
      completed the Short Form-36 Health Survey (SF-36). We used valid and reliable
      methods to classify subjects as frail or non-frail according to Johansen's et al.
      (2007) criteria. A one-way analysis of variance (ANOVA) and chi-square tests were
      used to compare the groups. In addition, Spearman's correlation analysis was
      conducted to measure associations between identified variables and frailty. We
      also performed simple linear regression using the SF-36 physical and mental
      composite scores. RESULTS: Almost half of the sample (42.6%) exhibited evidence
      of frailty. The groups differed significantly in terms of age, gender, and all SF
      36 domains, excluding Social Functioning and Role Emotional. Frailty was
      significantly associated with all SF-36 domains, again excluding Social
      Functioning and Role Emotional. Regression analysis revealed no significant
      between-group differences in composite physical and mental health scores
      generated by the SF-36 (p > 0.05). CONCLUSION: Frail and non-frail CKD patients
      differed significantly in seven of the eight SF-36 domains. The frail group
      displayed diminished physical and mental functioning when their SF-36 scores were
      divided by their physical and mental composite scores. Frailty was correlated
      with QOL domains, with the exception of the social domain. There is a need for
      interventions targeting the characteristics of frailty, to provide better
      treatment and optimize overall QOL.

PMID- 24580962
TI  - Assessing the risk of Nipah virus establishment in Australian flying-foxes.
AB  - Nipah virus (NiV) is a recently emerged zoonotic virus that causes severe disease
      in humans. The reservoir hosts for NiV, bats of the genus Pteropus (known as
      flying-foxes) are found across the Asia-Pacific including Australia. While NiV
      has not been detected in Australia, evidence for NiV infection has been found in
      flying-foxes in some of Australia's closest neighbours. A qualitative risk
      assessment was undertaken to assess the risk of NiV establishing in Australian
      flying-foxes through flying-fox movements from nearby regions. Events surrounding
      the emergence of new diseases are typically uncertain and in this study an expert
      opinion workshop was used to address gaps in knowledge. Given the difficulties in
      combining expert opinion, five different combination methods were analysed to
      assess their influence on the risk outcome. Under the baseline scenario where the
      median was used to combine opinions, the risk was estimated to be very low.
      However, this risk increased when the mean and linear opinion pooling combination
      methods were used. This assessment highlights the effects that different methods
      for combining expert opinion have on final risk estimates and the caution needed
      when interpreting these outcomes given the high degree of uncertainty in expert
      opinion. This work has provided a flexible model framework for assessing the risk
      of NiV establishment in Australian flying-foxes through bat movements which can
      be updated when new data become available. 

PMID- 24580961
TI  - Intelligent neonatal monitoring based on a virtual thermal sensor.
AB  - BACKGROUND: Temperature measurement is a vital part of daily neonatal care.
      Accurate measurements are important for detecting deviations from normal values
      for both optimal incubator and radiant warmer functioning. The purpose of
      monitoring the temperature is to maintain the infant in a thermoneutral
      environmental zone. This physiological zone is defined as the narrow range of
      environmental temperatures in which the infant maintains a normal body
      temperature without increasing his or her metabolic rate and thus oxygen
      consumption. Although the temperature measurement gold standard is the skin
      electrode, infrared thermography (IRT) should be considered as an effortless and
      reliable tool for measuring and mapping human skin temperature distribution and
      assist in assessing thermoregulatory reflexes. METHODS: Body surface temperature
      was recorded under several clinical conditions using an infrared thermography
      imaging technique. Temperature distributions were recorded as real-time video,
      which was analyzed to evaluate mean skin temperatures. Emissivity variations were
      considered for optimal neonatal IRT correction for which the compensation vector
      was overlaid on the tracking algorithm to improve the temperature reading.
      Finally, a tracking algorithm was designed for active follow-up of the defined
      region of interest over a neonate's geometry. RESULTS: The outcomes obtained from
      the thermal virtual sensor demonstrate its ability to accurately track different
      geometric profiles and shapes over the external anatomy of a neonate. Only a
      small percentage of the motion detection attempts failed to fit tracking
      scenarios due to the lack of a properly matching matrix for the ROI profile over
      neonate's body surface. CONCLUSIONS: This paper presents the design and
      implementation of a virtual temperature sensing application that can assist
      neonatologists in interpreting a neonate's skin temperature patterns. Regarding
      the surface temperature, the influence of different environmental conditions
      inside the incubator has been confirming.

PMID- 24580963
TI  - A combination of two variants in PRKAG3 is needed for a positive effect on meat
      quality in pigs.
AB  - BACKGROUND: Color and pH of meat measured 24 h post mortem are common selection
      objectives in pig breeding programs. Several amino acid substitutions in PRKAG3
      have been associated with various meat quality traits. In our previous study
      ASGA0070625, a SNP next to PRKAG3, had the most significant association with meat
      quality traits in the Finnish Yorkshire. However, the known amino acid
      substitutions, including I199V, did not show any association. The aims of this
      study were to characterize further variation in PRKAG3 and its promoter region,
      and to test the association between these variants and the pH and color of pork
      meat. RESULTS: The data comprised of 220 Finnish Landrace and 230 Finnish
      Yorkshire artificial insemination boars with progeny information. We sequenced
      the coding and promoter region of PRKAG3 in these and in three additional wild
      boars. Genotypes from our previous genome-wide scans were also included in the
      data. Association between SNPs or haplotypes and meat quality traits (deregressed
      estimates of breeding values from Finnish national breeding value estimation for
      pH, color lightness and redness measured from loin or ham) was tested using a
      linear regression model. Sequencing revealed several novel amino acid
      substitutions in PRKAG3, including K24E, I41V, K131R, and P134L. Linkage
      disequilibrium was strong among the novel variants, SNPs in the promoter region
      and ASGA0070625, especially for the Yorkshire. The strongest associations were
      observed between ASGA0070625 and the SNPs in the promoter region and pH measured
      from loin in the Yorkshire and between I199V and pH measured from ham in the
      Landrace. In contrast, ASGA0070625 was not significantly associated with meat
      quality traits in the Landrace and I199V not in the Yorkshire. Haplotype analysis
      showed a significant association between a haplotype consisting of 199I and 24E
      alleles (or g.-157C or g.-58A alleles in the promoter region) and pH measured
      from loin and ham in both breeds (P-values varied from 1.72 * 10-4 to 1.80 * 10
      8). CONCLUSIONS: We conclude that haplotype g.-157C - g.-58A - 24E - 199I in
      PRKAG3 has a positive effect on meat quality in pigs. Our results are readily
      applicable for marker-assisted selection in pigs.

PMID- 24580965
TI  - Dermatoscopic findings in cutaneous Rosai-Dorfman disease and response to low
      dose thalidomide.

PMID- 24580967
TI  - Enhanced rate performance of mesoporous Co(3)O(4) nanosheet supercapacitor
      electrodes by hydrous RuO(2) nanoparticle decoration.
AB  - Mesoporous cobalt oxide (Co3O4) nanosheet electrode arrays are directly grown
      over flexible carbon paper substrates using an economical and scalable two-step
      process for supercapacitor applications. The interconnected nanosheet arrays form
      a three-dimensional network with exceptional supercapacitor performance in
      standard two electrode configuration. Dramatic improvement in the rate capacity
      of the Co3O4 nanosheets is achieved by electrodeposition of nanocrystalline,
      hydrous RuO2 nanoparticles dispersed on the Co3O4 nanosheets. An optimum RuO2
      electrodeposition time is found to result in the best supercapacitor performance,
      where the controlled morphology of the electrode provides a balance between good
      conductivity and efficient electrolyte access to the RuO2 nanoparticles. An
      excellent specific capacitance of 905 F/g at 1 A/g is obtained, and a nearly
      constant rate performance of 78% is achieved at current density ranging from 1 to
      40 A/g. The sample could retain more than 96% of its maximum capacitance even
      after 5000 continuous charge-discharge cycles at a constant high current density
      of 10 A/g. Thicker RuO2 coating, while maintaining good conductivity, results in
      agglomeration, decreasing electrolyte access to active material and hence the
      capacitive performance. 

PMID- 24580966
TI  - Fiber effects in nutrition and gut health in pigs.
AB  - Dietary fiber is associated with impaired nutrient utilization and reduced net
      energy values. However, fiber has to be included in the diet to maintain normal
      physiological functions in the digestive tract. Moreover, the negative impact of
      dietary fiber will be determined by the fiber properties and may differ
      considerably between fiber sources. Various techniques can be applied to enhance
      nutritional value and utilization of available feed resources. In addition, the
      extent of fiber utilization is affected by the age of the pig and the pig breed.
      The use of potential prebiotic effects of dietary fiber is an attractive way to
      stimulate gut health and thereby minimize the use of anti-microbial growth
      promoters. Inclusion of soluble non-starch polysaccharides (NSP) in the diet can
      stimulate the growth of commensal gut microbes. Inclusion of NSP from chicory
      results in changes in gut micro-environment and gut morphology of pigs, while
      growth performance remains unaffected and digestibility was only marginally
      reduced. The fermentation products and pH in digesta responded to diet type and
      were correlated with shifts in the microbiota. Interestingly, fiber intake will
      have an impact on the expression of intestinal epithelial heat-shock proteins in
      the pig. Heat-shock proteins have an important physiological role in the gut and
      carry out crucial housekeeping functions in order to maintain the mucosal barrier
      integrity. Thus, there are increasing evidence showing that fiber can have
      prebiotic effects in pigs due to interactions with the gut micro-environment and
      the gut associated immune system. 

PMID- 24580964
TI  - NFkappaB-mediated CXCL1 production in spinal cord astrocytes contributes to the
      maintenance of bone cancer pain in mice.
AB  - BACKGROUND: Bone cancer pain (BCP) is one of the most disabling factors in
      patients suffering from primary bone cancer or bone metastases. Recent studies
      show several chemokines (for example, CCL2, CXCL10) in the spinal cord are
      involved in the pathogenesis of BCP. Here we investigated whether and how spinal
      CXCL1 contributes to BCP. METHODS: Mouse prostate tumor cell line, RM-1 cells
      were intramedullary injected into the femur to induce BCP. The mRNA expression of
      CXCL1 and CXCR2 was detected by quantitative real-time PCR. The protein
      expression and distribution of CXCL1, NFkappaB, and CXCR2 was examined by
      immunofluorescence staining and western blot. The effect of CXCL1 neutralizing
      antibody, NFkappaB antagonist, and CXCR2 antagonist on pain hypersensitivity was
      checked by behavioral testing. RESULTS: Intramedullary injection of RM-1 cells
      into the femur induced cortical bone damage and persistent (>21 days) mechanical
      allodynia and heat hyperalgesia. Tumor cell inoculation also produced CXCL1
      upregulation in activated astrocytes in the spinal cord for more than 21 days.
      Inhibition of CXCL1 by intrathecal administration of CXCL1 neutralizing antibody
      at 7 days after inoculation attenuated mechanical allodynia and heat
      hyperalgesia. In cultured astrocytes, TNF-alpha induced robust CXCL1 expression,
      which was dose-dependently decreased by NFkappaB inhibitor. Furthermore,
      inoculation induced persistent NFkappaB phosphorylation in spinal astrocytes.
      Intrathecal injection of NFkappaB inhibitor attenuated BCP and reduced CXCL1
      increase in the spinal cord. Finally, CXCR2, the primary receptor of CXCL1, was
      upregulated in dorsal horn neurons after inoculation. Inhibition of CXCR2 by its
      selective antagonist SB225002 attenuated BCP. CONCLUSION: NFkappaB mediates CXCL1
      upregulation in spinal astrocytes in the BCP model. In addition, CXCL1 may be
      released from astrocytes and act on CXCR2 on neurons in the spinal cord and be
      involved in the maintenance of BCP. Inhibition of the CXCL1 signaling may provide
      a new therapy for BCP management.

PMID- 24580968
TI  - The role of ultrasound in the management and diagnosis of infectious
      mononucleosis.
AB  - Currently, infectious mononucleosis (IM) is a clinically diagnosed condition.
      According to the American Family Physician criteria for IM, splenomegaly is the
      key factor that distinguishes IM from other causes of sore throat. Though
      heterophile antibody tests are often ordered to confirm diagnosis of IM, this
      test has a high false-negative rate early in the course of the disease. This case
      report provides an example of how the use of ultrasound to diagnose splenomegaly
      and subsequently mononucleosis increases diagnostic accuracy. 

PMID- 24580969
TI  - Nurse practitioner prescribing practice in Australia: confidence in aspects of
      medication management.
AB  - The findings of the 2010 national survey of nurse practitioner (NP) prescribing
      in Australia related to confidence in prescribing are reported. A significant
      correlation between years endorsed as a NP and prescribing confidence was found.
      NPs in Australia were significantly more confident in the prescribing aspects of
      commencing a new medication than adjusting or ceasing a medication prescribed by
      others. These findings are discussed in relation to promotion of the quality use
      of medicines and identification of potential strategies to promote the ongoing
      positive evolution of NP practice in Australia. 

PMID- 24580970
TI  - Women's decision satisfaction and psychological distress following early breast
      cancer treatment: a treatment decision support role for nurses.
AB  - This prospective cross-sectional study investigated Australian women's (n = 104)
      decision satisfaction with cancer treatment decision for early breast cancer as
      well as their psychological distress 3-4 months following surgery. Women's
      satisfaction was surveyed using the Treatment Decision Satisfaction
      Questionnaire, and the Brief Symptom Inventory-18 was used to measure
      psychological distress. Women who were living alone, who worked as professionals
      and who were not involved in the decision-making process by their doctors were
      less likely to be satisfied with their decision process, outcome and their
      overall treatment decision. Following treatment, 26.0% of women were distressed;
      18.3% experienced anxiety; 19.2% somatization; and 27.9% depression. Women who
      experienced somatization were more likely to be dissatisfied with the treatment
      decision (P = 0.003) as were those who reported psychological distress (P =
      0.020). Women who were involved in choosing their treatment were more satisfied
      with their decision. Many women experienced distress following breast cancer
      treatment and might have required referral for psychological assessment,
      management and long-term support. Women who experienced distress were more likely
      to be dissatisfied with the treatment decision (or vice versa).

PMID- 24580971
TI  - The role of intrinsic motivation in a group of low vision patients participating
      in a self-management programme to enhance self-efficacy and quality of life.
AB  - Self-management programmes have previously been found to decrease health
      problems, enhance quality of life and increase independence. However, there is no
      literature that examines the influence of the participants' intrinsic motivation
      on the outcomes of such programmes. This study examined the role of intrinsic
      motivation in a pilot low vision self-management programme to enhance self
      efficacy and quality of life of the programme participants. A positive
      association was observed between the female participants' perceived choice and
      perceived competence, two underlying dimensions of the Intrinsic Motivation
      Inventory. In addition, a positive correlation was observed between the younger
      participants' perceived competence and the change in their quality of life. The
      findings provide some support for consideration of participants' intrinsic
      motivation in the development of effective self-management programmes. 

PMID- 24580972
TI  - Preparing the future nurses for nursing research: a creative teaching strategy
      for RN-to-BSN students.
AB  - Developing effective teaching strategies to stimulate students' interest and
      enthusiasm are urgently needed in current research courses. The purposes of the
      study were to implement the Cookie Experiments teaching strategy in research
      course and examine the effects of the strategy on students' attitudes towards
      nursing research. The study was a pretest-post-test design with 95 students at a
      Registered Nurses to Bachelor of Science in Nursing (RN-to-BSN) program enrolled
      in the nursing research course. Results indicated that there was a significant
      effect of the Cookie Experiments teaching strategy on students' attitudes towards
      research. Although students perceived a median high score of pressure from the
      research course, they regarded that the pressure is conducive to their learning
      of research. Students highly suggested to continuously applying this teaching
      strategy in the future nursing research courses. Developing and using various
      teaching strategies with attractive and hands-on methods to motivate nurse
      students, learning research is strongly recommended. 

PMID- 24580973
TI  - The inter-rater reliability test of the modified Morse Fall Scale among patients
      >= 55 years old in an acute care hospital in Singapore.
AB  - A prospective, descriptive study was conducted in an acute care hospital in
      Singapore to determine the inter-rater reliability of the modified Morse Fall
      Scale by evaluating the degrees of agreement on the ratings of the individual
      items and overall score between the 'gold standard' assessor and the facility
      assessors. One hundred and forty-two subjects were recruited during the 1.5 month
      data collection period. The simple and weighted kappa-values were all > 0.8
      except for the item 'effects of medications' (kappa and kappaw  = 0.63), and the
      correlation coefficient (rs  = 0.89) was significantly high at a significance
      level of < 0.001. The modified Morse Fall Scale was shown to be a reliable fall
      risk assessment tool having a relative high inter-rater reliability level for the
      overall score and individual items. This study provides evidence-based
      psychometric support for the clinical application of this tool. 

PMID- 24580974
TI  - Are we ready for personalized cancer risk management? The view from breast-care
      providers.
AB  - Personalized medicine, the tailoring of prevention and treatment, is the future
      of routine clinical practice. This approach has started to appear in genetic
      testing for predisposition to hereditary breast and ovarian cancer (HBOC). We
      explored how breast-care providers perceived HBOC risk management, using grounded
      theory. This study found that the frontline healthcare providers perceived HBOC
      risk management as still being neglected in breast cancer care. Emerging
      challenges included treatment priority, hesitancy to deal with sensitive issues,
      easily missed risks, genetic data not being shared among multidisciplinary
      professionals, and patients being lost to follow-up. Oncology nurses are ideally
      placed to facilitate communication and utilization of genetic information among
      multidisciplinary professionals. Specialized outpatient clinics need to be
      established to follow up individuals at high risk. There is a need to create a
      system to meet the future demands of personalized medicine in nursing practice. 

PMID- 24580975
TI  - Hand hygiene compliance among the nursing staff in freestanding nursing homes in
      Taiwan: a preliminary study.
AB  - This study aimed to explore the hand hygiene compliance among the nursing staff
      in Taiwanese freestanding nursing homes. A descriptive observational research
      design was used. A total of 782 opportunities for hand hygiene were observed by
      one trained research assistant in two freestanding nursing homes. The hand
      hygiene observation tool was used to assess hand hygiene practice. The overall
      hand hygiene compliance among nursing staff in nursing homes was only 11.3%.
      Results further showed that the compliance was greater after contact with body
      fluids (odds ratio = 6.9, confidence interval (CI) = 3.75-9.88, P = 0.000) and
      lower before the performance of aseptic procedures (odds ratio = 0.15, CI = 0.04
      0.63, P = 0.003) when compared with other activities. Hand hygiene compliance was
      relatively low among the nursing staff in freestanding nursing homes in Taiwan.
      To comprehensively analyze this issue, further research involving a larger number
      of nursing homes and strategies to improve compliance with hand hygiene among the
      nursing staff at these institutions is needed. 

PMID- 24580976
TI  - Practice nurses and cervical screening: a two-country review.
AB  - The aim of this review is to explore the literature relating to the delivery of
      cervical screening by practice nurses (PNs) in the United Kingdom and Australia.
      Research relating to PNs began in earnest approximately 15 years ago in the UK
      context, and more recently, c.2005, in Australia. Although there is scant
      literature devoted specifically to the role of PNs in cervical screening,
      literature relating to the role of PNs provides evidence of the extent to which
      PNs in the United Kingdom and Australia are involved in the provision of cervical
      screening services. Findings from this review indicate that the role of PNs in
      the provision of cervical screening differs substantially between the United
      Kingdom and Australia. PNs in the United Kingdom provide a high percentage of
      cervical screening services, whereas in Australia general practitioners provide
      around 80% of all cervical smears, which account for only 0.6% of all procedures
      undertaken by PNs. Employment and funding models and inadequate multidisciplinary
      collaboration are contributing to the underutilization of PNs in Australia. 

PMID- 24580977
TI  - Reporting and methodological quality of systematic reviews or meta-analyses in
      nursing field in China.
AB  - The aim of this paper was to evaluate reporting and methodological quality of
      systematic reviews or meta-analyses in the nursing field in China. Over the last
      decade, evidence-based nursing has been gradually known and accepted by nurses in
      China, and the number of systematic reviews or meta-analyses of nursing flied has
      steadily increased, but the quality of these reviews is unsatisfactory. The
      Chinese Journal Full-Text Database, the Chinese Biomedicine Literature Database
      and the Wanfang Database were searched for systematic reviews or meta-analyses in
      the nursing field, from inception through December 2011. The Preferred Reporting
      Items of Systematic Reviews and Meta-analyses and the Assessment of Multiple
      Systematic Reviews checklists were used to assess reporting characteristics and
      methodological quality, respectively. A total of 63 systematic reviews or meta
      analyses were identified. The deficiencies of methodological quality were mainly
      in literature searches, heterogeneity handling, recognition and assessment of
      publication bias. In addition, the deficiencies of reporting characteristics were
      reflected in incomplete reporting of literature search, quality assessment, risk
      of bias and results. Focusing on improving the quality of reporting and
      methodological quality of systematic reviews or meta-analyses in the nursing
      field in China is urgently needed. 

PMID- 24580978
TI  - Predicting nurses' turnover intentions by demographic characteristics, perception
      of health, quality of work attitudes.
AB  - The purpose of this paper is to examine the impact of demographic variables,
      organizational commitment levels, perception of health and quality of work on
      turnover intentions. A self-reported cross-sectional survey design was used to
      collect data from Jordanian registered nurses who were working between June 2011
      and November 2011. The findings showed strong effects of the quality of work,
      perception of health and normative organizational commitments on turnover
      intentions. This study sheds the light on the important work outcomes in health
      care organizations. Increasing nursing quality of work and normative
      organizational commitment are good strategies for reducing turnover intentions. 

PMID- 24580979
TI  - The effect of long-term care and follow-up on complications in patients with
      external fixators.
AB  - The present study aimed to determine the effect of long-term care and follow-up
      on complications in patients with external fixators. This study was conducted as
      a study research. The study sample included a total of 60 patients treated with
      external fixators for fractures, of whom 30 were in the control and 30 were in
      the study group. No intervention was made on the control group patients. The
      patients in the study group received external fixator pin site wound care, pin
      site massage and neurovascular follow-up. The study group patients were also
      given discharge training about external fixator pin site care two days before
      their discharge and were also provided with training manuals to guide their home
      care. Both groups were visited weekly at their homes to record their
      complications. Nine complications developed in eight patients (26.7%) in the
      study group, and 19 complications developed in 19 patients (63.3%) in the control
      group. Pin site infections were 11.6% of the total sample. The percentage for pin
      loosening, stiff joint, nerve and vessel injury and pain and swelling was 5%,
      25%, 1.7% and 3.3%, respectively. 

PMID- 24580980
TI  - Antecedents to the integration process for recovery in older patients and spouses
      after a cardiovascular procedure.
AB  - Social isolation, psychological state and knowledge needs are important
      antecedents to the process of integration for recovery from cardiovascular (CV)
      procedures. The purpose of this study is to measure these antecedents at 6 and 12
      weeks after CV procedures in patients (greater 65 years) and their spouses. This
      descriptive study enrolled 318 subjects; 87 patients/73 spouses responded. There
      was higher spousal anxiety at 6 weeks (4.64 +/- 4.2) compared with 12 weeks (3.65
      +/- 3.3, t = -2.17, P < 0.032). Patients rated 10 and 7 self-care knowledge needs
      at 6 and 12 weeks as 'very important' with significant reductions in importance
      for 4 needs by 12 weeks. Spouses rated 14 and 10 knowledge needs as 'very
      important' at 6 and 12 weeks. There were three spouse care knowledge needs that
      were not met at 6 weeks. Data identified higher anxiety levels in spouses, and
      spouse needs that were unmet at 6 weeks after CV procedures. 

PMID- 24580981
TI  - Prevention of functional decline in older hospitalized patients: nurses should
      play a key role in safe and adequate care.
AB  - This paper presents a discussion of knowledge and awareness regarding prevention
      of functional decline in older hospitalized patients. Functional decline is
      experienced by 30-60% of the older hospitalized patients, resulting in decreased
      independence and other adverse health outcomes. One literature study and four
      cohort studies (total n = 1628) were conducted to develop and validate an
      instrument to identify older hospitalized patients at risk for functional
      decline. An evidence-based best practice was developed to improve the quality of
      care for older patients. This paper shows the relevance and the complexity of
      this problem and shows that patients at risk can be recognized by four simple
      questions. Due to their ability to observe and guide patients and their 24-h
      patient supervision, nurses should play a key role in strategies to prevent
      functional decline. Nurses should assess the geriatric needs in patients at risk
      and based on these initiate and coordinate multi-professional interventions.
      Given the growing number of older people in western society and the growing need
      for care, action to prevent functional decline cannot be withheld. Knowledge of
      the ageing process, implementation of an evidence-based programme and a
      multidisciplinary approach is a basic ingredient to prevent functional decline.

PMID- 24580984
TI  - Functional MRI in clinical practice: a pictorial essay.
AB  - In clinical practice, functional magnetic resonance imaging (fMRI) is a valuable
      non-invasive tool particularly during preoperative work-up of brain tumour and
      epilepsy patients. In this pictorial essay, we review expected areas of eloquent
      cortical activation during the four major clinical paradigms, discuss pitfalls
      related to fMRI and look at clinical examples where fMRI was particularly
      valuable in preoperative planning. 

PMID- 24580985
TI  - Necrotising soft tissue infection of the lower limb due to a perforated caecal
      carcinoma: a case report.
AB  - INTRODUCTION: We report the first case to our knowledge where an ascending
      colorectal tumour presented as a necrotising lower leg infection. CASE
      PRESENTATION: We describe the unusual presentation of a previously unknown caecal
      carcinoma in a 69-year-old Caucasian man, which presented as a rapidly spreading
      limb infection due to a perforated caecal adenocarcinoma. This case presented a
      diagnostic dilemma and we document the investigation and management in our
      patient and compare this to the current published literature. CONCLUSIONS:
      Although rare, this case highlights how leg swelling and in particular, thigh and
      gluteal swelling, have the potential to be an unusual presentation of a caecal
      carcinoma.

PMID- 24580983
TI  - Nutrition and physical activity randomized control trial in child care centers
      improves knowledge, policies, and children's body mass index.
AB  - BACKGROUND: To address the public health crisis of overweight and obese preschool
      age children, the Nutrition And Physical Activity Self Assessment for Child Care
      (NAP SACC) intervention was delivered by nurse child care health consultants with
      the objective of improving child care provider and parent nutrition and physical
      activity knowledge, center-level nutrition and physical activity policies and
      practices, and children's body mass index (BMI). METHODS: A seven-month
      randomized control trial was conducted in 17 licensed child care centers serving
      predominantly low income families in California, Connecticut, and North Carolina,
      including 137 child care providers and 552 families with racially and ethnically
      diverse children three to five years old. The NAP SACC intervention included
      educational workshops for child care providers and parents on nutrition and
      physical activity and consultation visits provided by trained nurse child care
      health consultants. Demographic characteristics and pre - and post-workshop
      knowledge surveys were completed by providers and parents. Blinded research
      assistants reviewed each center's written health and safety policies, observed
      nutrition and physical activity practices, and measured randomly selected
      children's nutritional intake, physical activity, and height and weight pre- and
      post-intervention. RESULTS: Hierarchical linear models and multiple regression
      models assessed individual- and center-level changes in knowledge, policies,
      practices and age- and sex-specific standardized body mass index (zBMI),
      controlling for state, parent education, and poverty level. Results showed
      significant increases in providers' and parents' knowledge of nutrition and
      physical activity, center-level improvements in policies, and child-level changes
      in children's zBMI based on 209 children in the intervention and control centers
      at both pre- and post-intervention time points. CONCLUSIONS: The NAP SACC
      intervention, as delivered by trained child health professionals such as child
      care health consultants, increases provider knowledge, improves center policies,
      and lowers BMI for children in child care centers. More health professionals
      specifically trained in a nutrition and physical activity intervention in child
      care are needed to help reverse the obesity epidemic. TRIAL REGISTRATION:
      National Clinical Trials Number NCT01921842.

PMID- 24580986
TI  - Neonatal resuscitation: improving the outcome.
AB  - Prudent veterinary intervention in the prenatal, parturient, and postpartum
      periods can increase neonatal survival by controlling or eliminating factors
      contributing to puppy morbidity and mortality. Postresuscitation or within the
      first 24 hours of a natural delivery, a complete physical examination should be
      performed by a veterinarian, technician, or knowledgeable breeder. Adequate
      ingestion of colostrum must occur promptly (within 24 hours) postpartum for
      puppies and kittens to acquire passive immunity.

PMID- 24580987
TI  - Pediatric clinical pathology.
AB  - This article provides clinically relevant and applicable information about normal
      biochemical values in puppies and kittens younger than 6 months, and is intended
      to provide practical guidelines for the interpretation of serum biochemical
      results in these young animals. At present there are no published sets of normal
      hematologic reference ranges for mixed-breed puppies and kittens younger than 6
      months. Reference-value sets for closed research colonies composed of a few
      selected breeds are available, which help to provide insight into trends in
      normal hematologic and biochemical values for puppies and kittens.

PMID- 24580988
TI  - Pros, cons, and techniques of pediatric neutering.
AB  - Pediatric gonadectomy is most commonly performed by humane organizations as a
      means of population control. Benefits and detriments of gonadectomy are reviewed,
      with special attention to literature describing effects specific to age at
      gonadectomy. Techniques for pediatric anesthesia and surgery are reviewed. 

PMID- 24580989
TI  - 2013 update on current vaccination strategies in puppies and kittens.
AB  - Vaccines remain one of the practitioner's greatest tools in preventing disease
      and maintaining individual and population health. This article is an update to
      "Current Vaccination Strategies in Puppies and Kittens" published in Veterinary
      Clinics of North America, Small Animal Practitioner, in May 2006. There are now
      comprehensive guidelines readily available for small animal practitioners
      regarding canine and feline pediatric (and adult) vaccination recommendations.
      Perhaps more importantly, there is an increased dialogue regarding all aspects of
      preventive medicine, of which vaccination is only a small, yet significant
      portion; and an increased drive to provide scientific evidence for developing
      vaccination recommendations. 

PMID- 24580990
TI  - Pediatric nutrition.
AB  - This article discusses pediatric nutrition in puppies and kittens.
      Supplementation of basic nutrients such as fat, protein, minerals, vitamins, and
      essential fatty acids of the bitch is essential for the proper growth and
      development of puppies during the lactation period. Milk replacers are compared
      for use in puppies and kittens. Supplements such as colostrum and probiotics for
      promotion of a healthy immune system and prevention or treatment of stress
      induced and weaning diarrhea are also discussed. 

PMID- 24580991
TI  - Pediatric seizure disorders in dogs and cats.
AB  - Seizure disorders in young animals pose different considerations as to cause and
      therapeutic decisions compared with adult animals. Infectious diseases of the
      nervous system are more likely in puppies and kittens compared with adults. The
      diagnosis of canine distemper is often based on clinical signs. Idiopathic
      epilepsy typically occurs in dogs between 1 and 5 years of age; however,
      inflammatory brain diseases such as necrotizing encephalitis and granulomatous
      meningoencephalomyelitis also commonly occur in young to middle-aged small-breed
      dogs. The choice of which anticonvulsant to administer for maintenance therapy is
      tailored to each individual patient.

PMID- 24580992
TI  - Canine pediatric dentistry.
AB  - The oral examination is an important part of the physical examination of every
      patient. In neonate and adolescent dogs, it is important to inspect the oral
      cavity for congenital and acquired dental and oral pathology. This article
      reviews the more common pediatric and juvenile dental anomalies that affect dogs
      in order to provide a resource for the basic understanding of the oral cavity in
      these patients. 

PMID- 24580993
TI  - Successful management permitting delayed operative revision of cleft palate in a
      labrador retriever.
AB  - Congenital palate defects (CP) occur in dogs. Secondary cleft palate (SCP) is a
      congenital oronasal fistula resulting in incomplete closure of the hard and soft
      palate. SCP occurs alone or in combination with primary cleft palate involving
      the lip and premaxilla. CP results from incomplete fusion of the palatine
      shelves, most critical at 25 to 28 days gestation. Methods to improve survival of
      puppies with CP are sought by clients. This case report illustrates a successful
      method to manage nutrition in affected dogs until adult size is attained,
      facilitating surgical correction.

PMID- 24580994
TI  - Pediatric feline upper respiratory disease.
AB  - Infectious feline upper respiratory tract disease (URTD) continues to be a
      widespread and important cause of morbidity and mortality in kittens. Multiple
      pathogens can contribute to URTD in kittens, and coinfections are common in
      overcrowded environments and contribute to increased disease severity. Worldwide,
      the most prevalent pathogens are feline herpesvirus-1 and feline calicivirus.
      Primary bacterial causes of URTD in cats include Bordetella bronchiseptica,
      Chlamydia felis, and Mycoplasma species. Streptococcus canis and Streptococcus
      equi subspecies zooepidemicus occasionally play a role as primary pathogens in
      shelter situations and catteries. This article reviews the major causes of
      disease in kittens, and provides an update on treatment and prevention
      strategies. 

PMID- 24580995
TI  - Diagnosis and management of urinary ectopia.
AB  - Ectopic ureters are the most common cause of urinary incontinence in young dogs
      but should be considered as a differential in any incontinent dog for which the
      history is not known. Ectopic ureters can be diagnosed with excretory urography,
      fluoroscopic urethrography or ureterography, abdominal ultrasonography,
      cystoscopy, helical computed tomography, or a combination of these diagnostic
      procedures. Other congenital abnormalities can also occur in dogs with ectopic
      ureters, including renal agenesis or dysplasia, hydronephrosis, and/or
      hydroureter and vestibulovaginal anomalies; therefore, the entire urinary system
      must be evaluated with ultrasonography if cystoscopy is the only other diagnostic
      tool used before surgery. Novel surgical techniques and adjunctive medical
      management have improved the prognosis for dogs with urinary ectopia. 

PMID- 24580996
TI  - Holistic pediatric veterinary medicine.
AB  - Holistic veterinary medicine treats the whole patient including all physical and
      behavioral signs. The root cause of disease is treated at the same time as
      accompanying clinical signs. Herbal and nutritional supplements can help support
      tissue healing and proper organ functioning, thereby reducing the tendency of
      disease progression over time. Proper selection of homeopathic remedies is based
      on detailed evaluation of clinical signs. Herbal medicines are selected based on
      organ(s) affected and the physiologic nature of the imbalance. Many herbal and
      nutraceutical companies provide support for veterinarians, assisting with proper
      formula selection, dosing, drug interactions, and contraindications. 

PMID- 24580997
TI  - Preface: update: small animal pediatrics.

PMID- 24580999
TI  - Vitamin D in public health nutrition.

PMID- 24581000
TI  - Early-life vitamin D deficiency and childhood-onset coeliac disease.
AB  - Many studies have investigated the aetiological roles of genetic and
      environmental factors in coeliac disease (CD) with the long-term goal of
      developing an effective primary prevention strategy. CD is a condition with
      dysregulated systemic and intestinal mucosal immune responses to dietary gluten
      proteins among genetically predisposed individuals. We recently described spring
      birth as a novel risk factor for CD in children. We believe that the association
      between season of birth and CD is due to seasonal differences in sunlight
      exposure and subsequent vitamin D status. Concomitant with global increases in CD
      prevalence, vitamin D deficiency also is increasingly recognized in children
      worldwide. Recent studies have shown that vitamin D deficiency can cause improper
      immune responses, abnormal intestinal mucosal integrity and impaired local
      defence to pathogenic microbial agents. In conjunction with other potential
      aetiological factors, we propose a hypothesis model of early-life vitamin D
      deficiency in the pathogenesis of childhood-onset CD. 

PMID- 24580998
TI  - Autism-epilepsy phenotype with macrocephaly suggests PTEN, but not GLIALCAM,
      genetic screening.
AB  - BACKGROUND: With a complex and extremely high clinical and genetic heterogeneity,
      autism spectrum disorders (ASD) are better dissected if one takes into account
      specific endophenotypes. Comorbidity of ASD with epilepsy (or paroxysmal EEG) has
      long been described and seems to have strong genetic background. Macrocephaly
      also represents a well-known endophenotype in subgroups of ASD individuals, which
      suggests pathogenic mechanisms accelerating brain growth in early development and
      predisposing to the disorder. We attempted to estimate the association of gene
      variants with neurodevelopmental disorders in patients with autism-epilepsy
      phenotype (AEP) and cranial overgrowth, analyzing two genes previously reported
      to be associated with autism and macrocephaly. METHODS: We analyzed the coding
      sequences and exon-intron boundaries of GLIALCAM, encoding an IgG-like cell
      adhesion protein, in 81 individuals with Autism Spectrum Disorders, either with
      or without comorbid epilepsy, paroxysmal EEG and/or macrocephaly, and the PTEN
      gene in the subsample with macrocephaly. RESULTS: Among 81 individuals with ASD,
      31 had concurrent macrocephaly. Head circumference, moreover, was over the 99.7th
      percentile ("extreme" macrocephaly) in 6/31 (19%) patients. Whilst we detected in
      GLIALCAM several single nucleotide variants without clear pathogenic effects, we
      found a novel PTEN heterozygous frameshift mutation in one case with "extreme"
      macrocephaly, autism, intellectual disability and seizures. CONCLUSIONS: We did
      not find a clear association between GLIALCAM mutations and AEP-macrocephaly
      comorbidity. The identification of a novel frameshift variant of PTEN in a
      patient with "extreme" macrocephaly, autism, intellectual disability and
      seizures, confirms this gene as a major candidate in the ASD-macrocephaly
      endophenotype. The concurrence of epilepsy in the same patient also suggests that
      PTEN, and the downstream signaling pathway, might deserve to be investigated in
      autism-epilepsy comorbidity. Working on clinical endophenotypes might be of help
      to address genetic studies and establish actual causative correlations in autism
      epilepsy.

PMID- 24581001
TI  - Endoscopic tissue sampling of the bile duct: can we do better?

PMID- 24581002
TI  - Transcriptome analyses and differential gene expression in a non-model fish
      species with alternative mating tactics.
AB  - BACKGROUND: Social dominance is important for the reproductive success of males
      in many species. In the black-faced blenny (Tripterygion delaisi) during the
      reproductive season, some males change color and invest in nest making and
      defending a territory, whereas others do not change color and 'sneak'
      reproductions when females lay their eggs. Using RNAseq, we profiled differential
      gene expression between the brains of territorial males, sneaker males, and
      females to study the molecular signatures of male dimorphism. RESULTS: We found
      that more genes were differentially expressed between the two male phenotypes
      than between males and females, suggesting that during the reproductive period
      phenotypic plasticity is a more important factor in differential gene expression
      than sexual dimorphism. The territorial male overexpresses genes related to
      synaptic plasticity and the sneaker male overexpresses genes involved in
      differentiation and development. CONCLUSIONS: Previously suggested candidate
      genes for social dominance in the context of alternative mating strategies seem
      to be predominantly species-specific. We present a list of novel genes which are
      differentially expressed in Tripterygion delaisi. This is the first genome-wide
      study for a molecular non-model species in the context of alternative mating
      strategies and provides essential information for further studies investigating
      the molecular basis of social dominance.

PMID- 24581004
TI  - Numerical predictors of arithmetic success in grades 1-6.
AB  - Math relies on mastery and integration of a wide range of simpler numerical
      processes and concepts. Recent work has identified several numerical competencies
      that predict variation in math ability. We examined the unique relations between
      eight basic numerical skills and early arithmetic ability in a large sample (N =
      1391) of children across grades 1-6. In grades 1-2, children's ability to judge
      the relative magnitude of numerical symbols was most predictive of early
      arithmetic skills. The unique contribution of children's ability to assess
      ordinality in numerical symbols steadily increased across grades, overtaking all
      other predictors by grade 6. We found no evidence that children's ability to
      judge the relative magnitude of approximate, nonsymbolic numbers was uniquely
      predictive of arithmetic ability at any grade. Overall, symbolic number
      processing was more predictive of arithmetic ability than nonsymbolic number
      processing, though the relative importance of symbolic number ability appears to
      shift from cardinal to ordinal processing.

PMID- 24581003
TI  - Efficiency of antenatal care and childbirth services in selected primary health
      care facilities in rural Tanzania: a cross-sectional study.
AB  - BACKGROUND: Cost studies are paramount for demonstrating how resources have been
      spent and identifying opportunities for more efficient use of resources. The main
      objective of this study was to assess the actual dimension and distribution of
      the costs of providing antenatal care (ANC) and childbirth services in selected
      rural primary health care facilities in Tanzania. In addition, the study analyzed
      determining factors of service provision efficiency in order to inform health
      policy and planning. METHODS: This was a retrospective quantitative cross
      sectional study conducted in 11 health centers and dispensaries in Lindi and
      Mtwara rural districts. Cost analysis was carried out using step down cost
      accounting technique. Unit costs reflected efficiency of service provision.
      Multivariate regression analysis on the drivers of observed relative efficiency
      in service provision between the study facilities was conducted. Reported
      personnel workload was also described. RESULTS: The health facilities spent on
      average 7 USD per capita in 2009. As expected, fewer resources were spent for
      service provision at dispensaries than at health centers. Personnel costs
      contributed a high approximate 44% to total costs. ANC and childbirth consumed
      approximately 11% and 12% of total costs; and 8% and 10% of reported service
      provision time respectively. On average, unit costs were rather high, 16 USD per
      ANC visit and 79.4 USD per childbirth. The unit costs showed variation in
      relative efficiency in providing the services between the health facilities. The
      results showed that efficiency in ANC depended on the number of staff, structural
      quality of care, process quality of care and perceived quality of care.
      Population-staff ratio and structural quality of basic emergency obstetric care
      services highly influenced childbirth efficiency. CONCLUSIONS: Differences in the
      efficiency of service provision present an opportunity for efficiency
      improvement. Taking into consideration client heterogeneity, quality improvements
      are possible and necessary. This will stimulate utilization of ANC and childbirth
      services in resource-constrained health facilities. Efficiency analyses through
      simple techniques such as measurement of unit costs should be made standard in
      health care provision, health managers can then use the performance results to
      gauge progress and reward efficiency through performance based incentives.

PMID- 24581005
TI  - Oral health associated with quality of life of people living with HIV/AIDS in
      Brazil.
AB  - BACKGROUND: The epidemic of HIV/AIDS enters into its fourth decade and is still
      considered an important public health problem in developed and developing
      countries. The purpose is verify the oral health and other factors that influence
      the quality of life of people living with HIV/AIDS attending a public service
      reference in Brazil. METHODS: The participants answered the questionnaire on
      socio-demographic conditions, issues related to HIV and daily habits. The quality
      of life was analyzed by the HIV/AIDS Targeted Quality of Life (HAT-QoL)
      instrument with 42 items divided into nine domains: General Activity, Sexual
      Activity, Confidentiality concerns, Health Concerns, Financial Concern, HIV
      Awareness, Satisfaction with Life Issues related to medication and Trust in the
      physician. The oral health data were collected by means of the DMFT index, use
      and need of dentures and the Community Periodontal Index, according to the
      criteria proposed by the World Health Organization, by a calibrated researcher.
      Bivariate and multiple linear regressions were performed. RESULTS: Of the
      participants, 53.1% were women and had a mean age of 42 years, 53.1% had eight
      years or less of schooling and 20.3% were not employed. In analyzing the quality
      of life domain of the HAT-QoL, with a lower average there was: Financial concern
      (39.4), followed by Confidentiality concern (43.2), Sexual activities (55.2) and
      Health concerns (62. 88). There was an association between the variables: do not
      have link to employment (p <0.001), is brown or black (p = 0.045), alcohol
      consumption (p = 0.041), did not make use of antiretroviral therapy (p = 0.006),
      high levels of viral load (p = 0.035) and need for dentures (p = 0.025), with the
      worse quality of life scores. CONCLUSION: Socioeconomic and inadequate health
      conditions had a negative impact on the quality of life of people with HIV/AIDS.

PMID- 24581006
TI  - Are habitat fragmentation, local adaptation and isolation-by-distance driving
      population divergence in wild rice Oryza rufipogon?
AB  - Habitat fragmentation weakens the connection between populations and is
      accompanied with isolation by distance (IBD) and local adaptation (isolation by
      adaptation, IBA), both leading to genetic divergence between populations. To
      understand the evolutionary potential of a population and to formulate proper
      conservation strategies, information on the roles of IBD and IBA in driving
      population divergence is critical. The putative ancestor of Asian cultivated rice
      (Oryza sativa) is endangered in China due to habitat loss and fragmentation. We
      investigated the genetic variation in 11 Chinese Oryza rufipogon populations
      using 79 microsatellite loci to infer the effects of habitat fragmentation, IBD
      and IBA on genetic structure. Historical and current gene flows were found to be
      rare (mh  = 0.0002-0.0013, mc  = 0.007-0.029), indicating IBD and resulting in a
      high level of population divergence (FST  = 0.343). High within-population
      genetic variation (HE  = 0.377-0.515), relatively large effective population
      sizes (Ne  = 96-158), absence of bottlenecks and limited gene flow were found,
      demonstrating little impact of recent habitat fragmentation on these populations.
      Eleven gene-linked microsatellite loci were identified as outliers, indicating
      local adaptation. Hierarchical AMOVA and partial Mantel tests indicated that
      population divergence of Chinese O. rufipogon was significantly correlated with
      environmental factors, especially habitat temperature. Common garden trials
      detected a significant adaptive population divergence associated with latitude.
      Collectively, these findings imply that IBD due to historical rather than recent
      fragmentation, followed by local adaptation, has driven population divergence in
      O. rufipogon. 

PMID- 24581008
TI  - Q&A: Targeting metabolism to diagnose and treat cancer.

PMID- 24581007
TI  - Mental health outcomes of mothers who conceived using fertility treatment.
AB  - OBJECTIVE: To compare the proportion of women with self-reported depression and
      anxiety symptoms at four months postpartum between mothers of singletons who
      conceived spontaneously and mothers who conceived with the aid of fertility
      treatment. METHODS: The sample used for this study was drawn from The "All Our
      Babies Study", a community-based prospective cohort of 1654 pregnant women who
      received prenatal care in Calgary, Alberta. This analysis included women
      utilizing fertility treatment and a randomly selected 1:2 comparison group. The
      data was collected via three questionnaires, two of which were mailed to the
      participants during pregnancy and one at four months postpartum. Symptoms of
      depression and anxiety at four months postpartum were measured using the Edinburg
      Postnatal Depression Scale and the Spielberger State Anxiety Inventory. Secondary
      outcomes of parenting morale and perceived stress were also evaluated.
      Descriptive statistics were used to characterize the population. Chi square tests
      and in cases of small cell sizes, Fisher Exact Tests were used to assess
      differences in postpartum mental health symptomatology between groups. RESULTS:
      Seventy-six participants (5.9%) conceived using a form of fertility treatment. At
      four months postpartum, no significant differences were observed in the
      proportions reporting excessive depression symptoms (2.6% vs. 5.3%, p = 0.50),
      anxiety (8.1% vs. 16.9%, p = 0.08) or high perceived stress scores (7.9% vs.
      13.3%, p = 0.23). Women who conceived with fertility treatment were less likely
      to score low on parenting morale compared to women who conceived spontaneously
      and this was particularly evident in primiparous women (12.5% vs. 33.8%, p =
      0.01). There were no group differences in proportions reporting low parenting
      morale in multiparous women. CONCLUSION: This study suggests that at four months
      postpartum, the proportion of women who experience elevated symptoms of
      depression, anxiety or perceived stress do not differ between mothers who
      conceive using fertility treatment and those who conceive spontaneously.
      Parenting morale at four months postpartum is significantly lower in primiparous
      mothers conceiving spontaneously compared to those who conceive with fertility
      treatment.

PMID- 24581009
TI  - Molecular clocks ticking in the court room.

PMID- 24581012
TI  - Medical students' perceptions of their role as covert observers of hand hygiene.
AB  - BACKGROUND: Medical students served as covert observers of hand hygiene (HH)
      compliance by health care workers (HCWs) during a recent 1-year study at a
      teaching hospital in Taiwan. This report describes the students' experience and
      their views of the major factors that led to good or poor compliance. METHODS:
      Nine upper class medical students received a basic course in HH and attended a
      workshop using World Health Organization standard training materials. A
      standardized observation tool was used to collect data on HH performance by the
      HCWs. On completion of the study, structured face-to-face interviews were
      conducted to assess the students' experiences. RESULTS: The medical students
      observed a total of 17,742 HH opportunities during the study period. Eight of the
      9 students participated in the poststudy interviews. Overall, the students
      believed that they had gained considerable knowledge of the attitudes regarding
      HH compliance by nurses, physicians, and surgeons according to each of the 5 HH
      indications. Based on their experience, they recommended that compliance could be
      improved by ensuring an adequate supply of HH products and by promoting role
      modeling in the ward, reminding, education in small groups, and objective
      structured clinical examinations. CONCLUSIONS: The opportunity for medical
      students to serve as covert observers broadened their knowledge of how infections
      are transmitted in hospitals and of the barriers that must be overcome to improve
      HCWs' HH compliance.

PMID- 24581011
TI  - Status of the implementation of the World Health Organization multimodal hand
      hygiene strategy in United States of America health care facilities.
AB  - BACKGROUND: The World Health Organization (WHO) launched a multimodal strategy
      and campaign in 2009 to improve hand hygiene practices worldwide. Our objective
      was to evaluate the implementation of the strategy in United States health care
      facilities. METHODS: From July through December 2011, US facilities participating
      in the WHO global campaign were invited to complete the Hand Hygiene Self
      Assessment Framework online, a validated tool based on the WHO multimodal
      strategy. RESULTS: Of 2,238 invited facilities, 168 participated in the survey
      (7.5%). A detailed analysis of 129, mainly nonteaching public facilities (80.6%),
      showed that most had an advanced or intermediate level of hand hygiene
      implementation progress (48.9% and 45.0%, respectively). The total Hand Hygiene
      Self-Assessment Framework score was 36 points higher for facilities with staffing
      levels of infection preventionists > 0.75/100 beds than for those with lower
      ratios (P = .01) and 41 points higher for facilities participating in hand
      hygiene campaigns (P = .002). CONCLUSION: Despite the low response rate, the
      survey results are unique and allow interesting reflections. Whereas the level of
      progress of most participating facilities was encouraging, this may reflect
      reporting bias, ie, better hospitals more likely to report. However, even in
      respondents, further improvement can be achieved, in particular by embedding hand
      hygiene in a stronger institutional safety climate and optimizing staffing levels
      dedicated to infection prevention. These results should encourage the launch of a
      coordinated national campaign and higher participation in the WHO global
      campaign.

PMID- 24581013
TI  - Lessons learned from earthquake-related tuberculosis exposures in a community
      shelter, Japan, 2011.
AB  - BACKGROUND: Refugees and displaced populations after natural disasters have been
      vulnerable to tuberculosis. We report an active pulmonary tuberculosis case at a
      shelter and the subsequent contact investigation and review lessons learned from
      the 2011 Great East Japan Earthquake. METHODS: The contact investigation was
      conducted to identify latent tuberculosis infection among a total of 95 contact
      persons, including 78 evacuees at the shelter, who were exposed to the index
      tuberculosis patient. The association between exposure time of contacts to a
      patient with active tuberculosis and results of interferon-gamma release assay
      (IGRA) was also examined. RESULTS: IGRA was positive in 9 (12.3%) of 73 evacuees
      at the shelter. Contacts who were exposed to active tuberculosis for more than 25
      days were significantly more likely to be IGRA positive, compared with contacts
      exposed for less than 20 days. All of the 4 evacuees with latent tuberculosis
      infection who initiated treatment completed the regimen successfully. CONCLUSION:
      When a disaster strikes and many people are living in shelters, it is essential
      for health care personnel to first suspect tuberculosis and implement prevention
      and control in collaboration with referral hospitals and public health centers.

PMID- 24581014
TI  - Staphylococcus aureus dispersal from healthy volunteers.
AB  - BACKGROUND: Understanding Staphylococcus aureus dispersal from human carriers is
      vital for preventing transmission and colonization of this organism in health
      care settings. This study investigated the S aureus supershedder hypothesis in
      relation to attributes of healthy volunteers. METHODS: Microbial aerosol
      generation from volunteers was quantified within a controlled environmental
      chamber during walking or sitting activities. Biological air samplers were used
      to determine numbers of total S aureus colony-forming units disseminated during
      these activities. RESULTS: A total of 17 volunteers was sampled on 3 occasions.
      Hairstyle (long hair tied up or a shaved head) was the only significant predictor
      of dissemination of S aureus (5% significance level). No other significant
      effects were found at the 5% level. A negative binomial distribution provides the
      best fit with respect to S aureus. CONCLUSION: We found that, in the context of
      our small sample size, hairstyle (long hair tied up or a shaved head)
      statistically affected levels of bacteria shed from volunteers. However, we found
      no evidence for "supershedders" or "cloud adults," suggesting they are at an
      extreme end of a continuous distribution.

PMID- 24581015
TI  - Human patient simulation education in the nursing management of patients
      requiring mechanical ventilation: a randomized, controlled trial.
AB  - BACKGROUND: Knowledge among critical care nurses and their adherence to evidence
      based guidelines for preventing ventilator-associated pneumonia is reported to be
      low. The aim of our study was to evaluate the effectiveness of human patient
      simulation (HPS) education in the nursing management of patients requiring
      mechanical ventilation. METHODS: A prospective, parallel, randomized controlled
      trial with repeated measurements was conducted in a 22-bed adult mixed medical
      surgical intensive care unit in Finland from February-October 2012. Thirty
      critical care nurses were allocated evenly to intervention and control groups (n
      = 15 each). The effectiveness of HPS education was evaluated through the
      validated Ventilator Bundle Questionnaire and Ventilator Bundle Observation
      Schedule at baseline and repeated twice-after the clinical and simulation
      settings, respectivley. RESULTS: After HPS education, the average skill scores
      (Ventilator Bundle Observation Schedule) in the intervention group increased
      significantly (46.8%-60.0% of the total score) in the final postintervention
      observation. In the average skill scores, a linear mixed model identified
      significant time (Pt < .001) and group (P(g) = .03) differences and time-group
      interactions (P(t*g) = .02) between the study groups after the HPS education. In
      contrast, the model did not identify any significant change over time (P(t) =
      .29) or time-group interactions (P(t) = .69) between groups in average knowledge
      scores (Ventilator Bundle Questionnaire). CONCLUSIONS: Our study identified
      significant transfer of learned skills to clinical practice following HPS
      education but no influence on the level of participants' factual knowledge.

PMID- 24581016
TI  - Extended-spectrum beta-lactamase-producing Klebsiella pneumoniae in the neonatal
      intensive care unit: does vancomycin play a role?
AB  - BACKGROUND: Extended-spectrum beta-lactamase (ESBL)-producing Klebsiella species
      cause worldwide problems in neonatal intensive care units (NICUs). This study
      aimed to determine possible risk factors for infection or colonization with ESBL
      producing Klebsiella pneumoniae (ESBLKp) during an outbreak in the NICU. METHODS:
      A retrospective cohort study was conducted among neonates admitted to the NICU of
      a teaching hospital in Riyadh, Saudi Arabia, during an outbreak of ESBLKp from
      April to July 2008. The incidence density ratio was calculated to determine
      possible predictors of ESBLKp colonization or infection. RESULTS: During 2,265
      person-days of follow-up of 118 neonates, 4 became infected, and 8 were colonized
      with ESBLKp. Univariate analyzes revealed that, among 14 neonates who were
      treated with vancomycin, 9 (64.3%) developed infection or colonization with
      ESBLKp, whereas, among 104 neonates who were not treated with vancomycin, 3
      (2.9%) were affected, with an incidence density ratio of 4.22 (95% confidence
      interval: 1.47-5.15). Parenteral feeding and mechanical ventilation were found to
      be marginally significant risk factors. CONCLUSION: Treatment with vancomycin
      appears to be a risk factor for infection or colonization with ESBLKp in the NICU
      setting.

PMID- 24581017
TI  - Effectiveness and cost of implementing an active surveillance screening policy
      for Acinetobacter baumannii: a Monte Carlo simulation model.
AB  - BACKGROUND: Acinetobacter baumannii infections are common and associated with
      high mortality and costs. Early identification of asymptomatic carriers can
      reduce patient-to-patient transmission, but the sensitivity of A baumannii
      surveillance tools is poor, and thus active surveillance is not routine practice.
      This study examined whether an active surveillance screening policy can reduce
      the transmission, mortality, and costs associated with A baumannii. METHODS: A
      simulation model was developed to determine the impact of active screening on
      patient outcomes. Model parameters included A baumannii prevalence, screening
      sensitivity and specificity, probability of transmission, progression from
      colonization to infection, mortality, and cost of screening, contact precautions,
      and infection. A scenario analysis was performed to evaluate the robustness of
      the results when varying the sensitivity of the screening test and the prevalence
      rate of A baumannii. RESULTS: Assuming a screening sensitivity of 55%, active
      screening reduced A baumannii transmissions, infections, and deaths by 48%. As
      the screening sensitivity approached 90%, the reduction in transmissions,
      infections, and deaths reached 78%. For all scenarios tested, active surveillance
      was cost saving (19%-53% reduction in mean hospital cost per patient) except at a
      carrier prevalence of <=2% and screening test sensitivity of <=55%. CONCLUSIONS:
      In institutions where A baumannii is endemic or during epidemics, implementing a
      surveillance program is cost-saving and can greatly reduce transmissions and
      deaths. Methodologies to improve the sensitivity of surveillance testing will
      help optimize the clinical impact of active screening programs on preventing the
      spread of A baumannii in health care facilities.

PMID- 24581018
TI  - The impact of influenza vaccination requirements for hospital personnel in
      California: knowledge, attitudes, and vaccine uptake.
AB  - BACKGROUND: Seasonal influenza infections are a leading cause of illness, death,
      and lost productivity. Vaccinating health care personnel (HCP) can reduce
      transmission of influenza virus to patients and reduce influenza-related
      absenteeism, enabling the health care system to meet elevated demand for care
      during influenza outbreaks. OBJECTIVES: We evaluated the impact of California's
      2006 influenza vaccination requirement for hospital workers (requiring
      vaccination or signed declinations) on uptake and vaccination-related attitudes,
      beliefs, and knowledge among hospital HCP. METHODS: We used a causal difference
      in-differences approach to compare changes over the prior 10 years in the self
      reported frequency of influenza vaccination for California hospital HCP and those
      from other states without similar laws using data from a stratified sample (N =
      3,529) of HCP drawn from online survey panels. We also examined cross-sectional
      differences in awareness of vaccination policies, promotion efforts, and
      attitudes toward influenza vaccination. All analyses used propensity score
      weighting to balance the observable characteristics of the 2 samples. RESULTS: We
      found that compared with their counterparts in other states, California hospital
      HCP were (1) more likely to report working under a formal written policy for
      influenza vaccination, (2) no more likely to be vaccinated, and (3) less likely
      to report working for an employer who provided financial incentives for
      vaccination or rewarded or recognized employees for being vaccinated. CONCLUSION:
      Our results suggest that state-level vaccination requirements such as those
      enacted by California, may not be sufficient to increase uptake among hospital
      HCP.

PMID- 24581019
TI  - Employee influenza vaccination in residential care facilities.
AB  - BACKGROUND: The organizational literature on infection control in residential
      care facilities is limited. Using a nationally representative dataset, we
      examined the organizational factors associated with implementing at least 1
      influenza-related employee vaccination policy/program, as well as the effect of
      vaccination policies on health care worker (HCW) influenza vaccine uptake in
      residential care facilities. METHODS: The study was a cross-sectional study using
      data from the 2010 National Survey of Residential Care Facilities. Multivariate
      logistic regression analysis was used to address the study's objectives. RESULTS:
      Facility size, director's educational attainment, and having a written influenza
      pandemic preparedness plan were significantly associated with the implementation
      of at least 1 influenza-related employee vaccination policy/program, after
      controlling for other facility-level factors. Recommending vaccination to
      employees, providing vaccination on site, providing vaccinations to employees at
      no cost, and requiring vaccination as a condition of employment were associated
      with higher employee influenza vaccination rates. CONCLUSION: Residential care
      facilities can improve vaccination rates among employees by adopting effective
      employee vaccination policies.

PMID- 24581020
TI  - Control of scabies outbreaks in an Italian hospital: an information-centered
      management strategy.
AB  - BACKGROUND: Scabies is a dermatologic infestation caused by Sarcoptes scabiei. In
      industrialized countries, hospitals and other health structures can sometimes be
      hit. The optimal management of scabies outbreaks still has to be established,
      mass prophylaxis being one possible option. METHODS: To identify the optimal
      approach to containing this re-emerging disease, a local health authority in
      Lombardy, Northern Italy, carried out an epidemiologic study into 2 scabies
      epidemics that took place from September to December 2012 in a 600-bed hospital
      with 26,000 admissions a year. RESULTS: Over a 3-month period, there were 12
      cases of scabies on 4 wards; 43 contacts received prophylaxis. When the first
      cases were identified, an information campaign involving all hospital personnel
      was immediately set up. Regular staff meetings were organized, and information
      leaflets were distributed to patients. Family doctors of discharged patients were
      informed of the outbreak. CONCLUSION: A management model based on an information
      centered strategy was used in place of mass prophylaxis to deal with scabies
      epidemics. The success of this approach was confirmed by the managers of the
      hospital involved (reduced expenditure for prophylactic drugs) and by hospital
      staff who did not have to deal with potential drug adverse effects.

PMID- 24581021
TI  - Chlorhexidine-silver sulfadiazine-impregnated venous catheters save costs.
AB  - BACKGROUND: Previous cost-effectiveness analyses have found that the use of
      chlorhexidine-silver sulfadiazine (CHSS)-impregnated catheters is associated with
      decreased catheter-related bloodstream infections (CRBSI) and central venous
      catheter (CVC)-related costs. However, in these analyses, the CVC-related cost
      included the increase of hospital stay. OBJECTIVE: Our aim was to determine the
      immediate CVC-related cost (including only the cost of CVC, diagnosis of CRBSI,
      and antimicrobials for the treatment of CRBSI) of using a CHSS or a standard
      catheter in internal jugular venous access. METHODS: We performed a prospective,
      observational, cohort study of patients admitted to the intensive care unit
      (ICU), Hospital Universitario de Canarias (Tenerife, Spain), who received 1 or
      more internal jugular venous catheters. RESULTS: The study included 245 CHSS
      impregnated catheters and 391 standard catheters. Exact logistic regression
      analysis showed that CHSS-impregnated catheters were associated with a lower
      incidence of CRBSI, controlling for catheter duration, than standard catheters (0
      vs 5.04 CRBSI per 1,000 catheter-days, respectively; odds ratio, 0.80; 95%
      confidence interval: 0.712-0.898; P < .001). Poisson regression showed that CHSS
      impregnated catheters were associated with lower CVC-related cost per day than
      standard catheters (?3.78 +/- ?4.45 vs ?7.28 +/- ?16.71, respectively; odds
      ratio, 0.52; 95% confidence interval: 0.504-0.535; P < .001). Survival analysis
      showed that CHSS-impregnated catheters were associated with increased CRBSI-free
      time compared with standard catheters (chi(2) = 14.9; P < .001). CONCLUSION: The
      use of CHSS-impregnated catheters reduced the incidence of CRBSI and immediate
      CVC-related costs in the internal jugular venous access.

PMID- 24581022
TI  - The value of ready-to-use disinfectant wipes: compliance, employee time, and
      costs.
AB  - Cleaning and disinfection practices of environmental surfaces are critical
      interventions for reducing health care-associated infections. We studied the
      value of ready-to-use cleaning and disinfection wipes compared with the
      traditional towel and bucket method. When using ready-to-use wipes, we found
      compliance to be significantly higher, a more rapid cleaning and disinfection
      process, and potential cost savings. Facilities should consider these products
      when making environmental services product selections. 

PMID- 24581023
TI  - Pharmacist participation in infection prevention: an innovative approach to
      monitoring compliance with the Five Moments for Hand Hygiene in a large academic
      medical center.
AB  - Using pharmacy residents as covert observers, we evaluated compliance with hand
      hygiene and contact precautions among 101 unique health care workers on entrance,
      exit, and inside rooms of patients with known or suspected Clostridium difficile
      infection. Overall compliance rates with hand hygiene upon entering and exiting
      patient rooms were 63.4% and 69.3%, respectively. However, there was a lack of
      hand hygiene inside patient rooms for the observed opportunities. 

PMID- 24581024
TI  - Patients' perception of infection prevention in dental practice.
AB  - Patient's perceptions of risk from bloodborne viruses (BBVs) and variant
      Creutzfeldt-Jacob Disease (vCJD) in relation to attendance at dental practice is
      understudied. This survey of an opportunistic sample of 50 dental practice
      patients examined patients' perceptions of the risk of acquiring BBVs and vCJD
      following dental treatment. Major concerns of patients revolved around hand
      hygiene practices rather than risks from BBVs or vCJD. No patient had avoided or
      delayed a visit to the dentist because of concerns over risks of cross infection.

PMID- 24581025
TI  - Emergence of extended-spectrum beta-lactamase-producing Escherichia coli in
      catheter-associated urinary tract infection in neurogenic bladder patients.
AB  - BACKGROUND: Catheter-associated urinary tract infection (CAUTI) is a common
      clinic problem. The purpose of this study was to investigate recent trends in
      CAUTI in neurogenic bladder patients focusing on extended-spectrum beta-lactamase
      (ESBL)-producing Escherichia coli. METHODS: Isolates from the urine of neurogenic
      bladder patients with UTI were investigated. Nine strains of ESBL-producing E
      coli were assayed by molecular strain typing using the Diversilab system for
      repetitive-sequence-based polymerase chain reaction (rep-PCR). RESULTS: E coli
      accounted for most of the bacteria (74.1% to 81.0%) that produced ESBLs. Rep-PCR
      data showed that 7 out of 9 ESBL-producing E coli belonged to the same typing
      group with high similarity (more than 97% similarity) and that this distribution
      corresponded with antibiotic resistance patterns. CONCLUSION: ESBL producing E
      coli strains isolated from CAUTI patients could be discriminated by rep-PCR
      typing using the Diversilab system in consistent with antibiotic resistance
      patterns.

PMID- 24581027
TI  - Occupational exposure to blood and compliance with standard precautions among
      health care workers in Beijing, China.
AB  - This cross-sectional survey assessed both risk and prevention of health care
      workers to bloodborne virus transmission in 2 hospitals in Beijing. The
      identified discrepancy between the high level of occupational blood exposure and
      suboptimal compliance with standard precautions underscores the urgent need for
      interventions to enhance occupational safety of health care workers in China. 

PMID- 24581026
TI  - Using electronic medical records to increase the efficiency of catheter
      associated urinary tract infection surveillance for National Health and Safety
      Network reporting.
AB  - BACKGROUND: Streamlining health care-associated infection surveillance is
      essential for health care facilities owing to the continuing increases in
      reporting requirements. METHODS: Stanford Hospital, a 583-bed adult tertiary care
      center, used their electronic medical record (EMR) to develop an electronic
      algorithm to reduce the time required to conduct catheter-associated urinary
      tract infection (CAUTI) surveillance in adults. The algorithm provides inclusion
      and exclusion criteria, using the National Healthcare Safety Network definitions,
      for patients with a CAUTI. The algorithm was validated by trained infection
      preventionists through complete chart review for a random sample of cultures
      collected during the study period, September 1, 2012, to February 28, 2013.
      RESULTS: During the study period, a total of 6,379 positive urine cultures were
      identified. The Stanford Hospital electronic CAUTI algorithm identified 6,101 of
      these positive cultures (95.64%) as not a CAUTI, 191 (2.99%) as a possible CAUTI
      requiring further validation, and 87 (1.36%) as a definite CAUTI. Overall, use of
      the algorithm reduced CAUTI surveillance requirements at Stanford Hospital by
      97.01%. CONCLUSIONS: The electronic algorithm proved effective in increasing the
      efficiency of CAUTI surveillance. The data suggest that CAUTI surveillance using
      the National Healthcare Safety Network definitions can be fully automated.

PMID- 24581029
TI  - The costs and benefits of diagnosis of ADHD: commentary on Holden et al.
AB  - In this journal, Holden, Jenkins-Jones, Poole, Morgan, Coghill and Currie , CAPMH
      7:34, 2013, report on the prevalence and financial costs of treating people with
      attention deficit hyperactivity disorder (ADHD) in the UK over the last ten
      years. We commend the authors on their thorough cost analysis, and discuss
      differences in prevalence estimates of diagnosed ADHD, that is the proportion of
      the child population with an ADHD diagnosis, which varies dramatically between
      studies. We also discuss the reasons for this. Regional variation in application
      of diagnostic criteria and clinical subjectivity are likely partial explanations.

PMID- 24581028
TI  - Electronic detection of bacteria using holey reduced graphene oxide.
AB  - Carbon nanomaterials have been widely explored for diverse biosensing
      applications including bacterial detection. However, covalent functionalization
      of these materials can lead to the destruction of attractive electronic
      properties. To this end, we utilized a new graphene derivative, holey reduced
      graphene oxide (hRGO), functionalized with Magainin I to produce a broad-spectrum
      bacterial probe. Unlike related carbon nanomaterials, hRGO retains the necessary
      electronic properties while providing the high percentage of available oxygen
      moieties required for effective covalent functionalization. 

PMID- 24581031
TI  - Acquired epidermodysplasia verruciformis in an HIV-infected patient.

PMID- 24581030
TI  - 256-MDCT for evaluation of urolithiasis: iterative reconstruction allows for a
      significant reduction of the applied radiation dose while maintaining high
      subjective and objective image quality.
AB  - PURPOSE: Multidetector CT (MDCT) is the established imaging modality in
      diagnostics of urolithiasis. The aim of iterative reconstruction (IR) is to allow
      for a radiation dose reduction while maintaining high image quality. This study
      evaluates its performance in MDCT for assessment of urolithiasis. MATERIALS AND
      METHODS: Fifty-two patients underwent non-contrast abdominal MDCT. Twenty-six
      patients were referred to MDCT under suspicion of urolithiasis, and examined
      using a dose-reduced scan protocol (RDCT). Twenty-six patients, who had undergone
      standard-dose MDCT, served as reference for radiation dose comparison. RDCT
      images were reconstructed using an IR system (iDose4TM, Philips Healthcare,
      Cleveland, OH, USA). Objective image noise (OIN) was recorded and five
      radiologists rated the subjective image quality independently. Radiation
      parameters were derived from the scan protocols. RESULTS: The CTDIvol could be
      reduced by 50% to 5.8 mGy (P < 0.0001). The same reduction was achieved for DLP
      and effective dose to 253 +/- 27 mGy*cm (P < 0.0001) and 3.9 +/- 0.4 mSv (P <
      0.0001). IR led to a reduction of the OIN of up to 61% compared with classic
      filtered back projection (FBP) (P < 0.0001). The OIN declined with increasing IR
      levels. RDCT with FBP showed the lowest scores of subjective image quality (2.32
      +/- 0.04). Mean scores improved with increasing IR levels. iDose6 was rated with
      the best mean score (3.66 +/- 0.04). CONCLUSION: The evaluated IR-tool and
      protocol may be applied to achieve a considerable radiation dose reduction in
      MDCT for diagnostics of urolithiasis while maintaining a confident image quality.
      Best image quality, suitable for evaluation of the entire abdomen concerning
      differential diagnoses, was achieved with iDose6.

PMID- 24581032
TI  - Where is the gap?: the contribution of disparities within developing countries to
      global inequalities in under-five mortality.
AB  - BACKGROUND: Global health equity strategists have previously focused much on
      differences across countries. At first glance, the global health gap appears to
      result primarily from disparities between the developing and developed regions.
      We examine how much of this disparity could be attributed to within-country
      disparities in developing nations. METHODS: We used data from Demographic and
      Health Surveys conducted between 1995 and 2010 in 67 developing countries. Using
      a population attributable risk approach, we computed the proportion of global
      under-five mortality gap and the absolute number of under-five deaths that would
      be reduced if the under-five mortality rate in each of these 67 countries was
      lowered to the level of the top 10% economic group in each country. As a
      sensitivity check, we also conducted comparable calculations using top 5% and the
      top 20% economic group. RESULTS: In 2007, approximately 6.6 million under-five
      deaths were observed in the 67 countries used in the analysis. This could be
      reduced to only 600,000 deaths if these countries had the same under-five
      mortality rate as developed countries. If the under-five mortality rate was
      lowered to the rate among the top 10% economic group in each of these countries,
      under-five deaths would be reduced to 3.7 million. This corresponds to a 48%
      reduction in the global mortality gap and 2.9 million under-five deaths averted.
      Using cutoff points of top 5% and top 20% economic groups showed reduction of 37%
      and 56% respectively in the global mortality gap. With these cutoff points,
      respectively 2.3 and 3.4 million under-five deaths would be averted. CONCLUSION:
      Under-five mortality disparities within developing countries account for roughly
      half of the global gap between developed and developing countries. Thus, within
      country inequities deserve as much consideration as do inequalities between the
      world's developing and developed regions.

PMID- 24581033
TI  - Medicaid spending on contraceptive coverage and pregnancy-related care.
AB  - OBJECTIVE: Up to 50% of pregnancies are unintended in the United States, and the
      healthcare costs associated with pregnancy are the most expensive among
      hospitalized conditions. The current study aims to assess Medicaid spending on
      various methods of contraception and on pregnancy care including unintended
      pregnancies. METHODS: We analyzed Medicaid health claims data from 2004 to 2010.
      Women 14-49 years of age initiating contraceptive methods and pregnant women were
      included as separate cohorts. Medicaid spending was summarized using mean all
      cause and contraceptive healthcare payments per patient per month (PPPM) over a
      follow-up period of up to 12 months. Medicaid payments were also estimated in
      2008 per female member of childbearing age per month (PFCPM) and per member per
      month (PMPM). Medicaid payments on unintended pregnancies were also evaluated
      PFCPM and PMPM in 2008. RESULTS: For short-acting reversible contraception (SARC)
      users, all-cause payments and contraceptive payments PPPM were respectively $365
      and $18.3 for oral contraceptive (OC) users, $308 and $19.9 for transdermal
      users, $215 and $21.6 for vaginal ring users, and $410 and $8.8 for injectable
      users. For long-acting reversible contraception (LARC) users (follow-up of 9-10
      months), corresponding payments were $194 and $36.8 for IUD users, and $237 and
      $29.9 for implant users. Pregnancy cohort all-cause mean healthcare payments PPPM
      were $610. Payments PFCPM and PMPM for contraceptives were $1.44 and $0.54, while
      corresponding costs of pregnancies were estimated at $39.91 and $14.81,
      respectively. Payments PFCPM and PMPM for contraceptives represented a small
      fraction at 6.56% ($1.44/$21.95) and 6.63% ($0.54/$8.15), respectively of the
      estimated payments for unintended pregnancy. CONCLUSIONS: This study of a large
      sample of Medicaid beneficiaries demonstrated that, over a follow-up period of 12
      months, Medicaid payments for pregnancy were considerably higher than payments
      for either SARC or LARC users. Healthcare payments for contraceptives represented
      a small proportion of payments for unintended pregnancy when considering the
      overall Medicaid population perspective in 2008.

PMID- 24581034
TI  - Oxfordshire Community Stroke Project classification improves prediction of post
      thrombolysis symptomatic intracerebral hemorrhage.
AB  - BACKGROUND: The Oxfordshire Community Stroke Project (OCSP) classification is a
      simple stroke classification system with value in predicting clinical outcomes.
      We investigated whether and how the addition of OCSP classification to the Safe
      Implementation of Thrombolysis in Stroke (SITS) symptomatic intracerebral
      hemorrhage (SICH) risk score improved the predictive performance. METHODS: We
      constructed an extended risk score by adding an OCSP component, which assigns 3
      points for total anterior circulation infarcts, 0 point for partial anterior
      circulation infarcts or lacunar infarcts. Patients with posterior circulation
      infarcts were assigned an extended risk score of zero. We analyzed prospectively
      collected data from 4 hospitals to compare the predictive performance between the
      original and the extended scores, using area under the receiver operating
      characteristic curve (AUC) and net reclassification improvement (NRI). RESULTS:
      In a total of 548 patients, the rates of SICH were 7.3% per the National
      Institute of Neurological Diseases and Stroke (NINDS) definition, 5.3% per the
      European-Australasian Cooperative Acute Stroke Study (ECASS) II, and 3.5% per the
      SITS-Monitoring Study (SITS-MOST). Both scores effectively predicted SICH across
      all three definitions. The extended score had a higher AUC for SICH per NINDS
      (0.704 versus 0.624, P = 0.015) and per ECASS II (0.703 versus 0.612, P = 0.016)
      compared with the SITS SICH risk score. NRI for the extended risk score was 22.3%
      (P = 0.011) for SICH per NINDS, 21.2% (P = 0.018) per ECASS II, and 24.5% (P =
      0.024) per SITS-MOST. CONCLUSIONS: Incorporation of the OCSP classification into
      the SITS SICH risk score improves risk prediction for post-thrombolysis SICH.

PMID- 24581035
TI  - A rare case of iliac crest metastasis from acinic cell carcinoma of parotid
      gland.
AB  - A case of acinic cell carcinoma of the right parotid gland metastasizing to the
      right iliac crest is presented. Generally, for this rare low-grade malignant
      salivary gland neoplasm, 20% of cases may have local recurrences whereas about
      10% of cases have distant metastases. They may arise many years after the initial
      presentation of the original tumor. The most frequent locations are the cervical
      lymph nodes, liver, lungs, contralateral orbit and bones. Occurrence in the
      appendicular skeleton is very rare and in our knowledge this is the first report
      of metastases to the pelvis. 

PMID- 24581037
TI  - The roles of family history of dyslexia, language, speech production and
      phonological processing in predicting literacy progress.
AB  - It is well established that speech, language and phonological skills are closely
      associated with literacy, and that children with a family risk of dyslexia (FRD)
      tend to show deficits in each of these areas in the preschool years. This paper
      examines what the relationships are between FRD and these skills, and whether
      deficits in speech, language and phonological processing fully account for the
      increased risk of dyslexia in children with FRD. One hundred and fifty-three 4-6
      year-old children, 44 of whom had FRD, completed a battery of speech, language,
      phonology and literacy tasks. Word reading and spelling were retested 6 months
      later, and text reading accuracy and reading comprehension were tested 3 years
      later. The children with FRD were at increased risk of developing difficulties in
      reading accuracy, but not reading comprehension. Four groups were compared: good
      and poor readers with and without FRD. In most cases good readers outperformed
      poor readers regardless of family history, but there was an effect of family
      history on naming and nonword repetition regardless of literacy outcome,
      suggesting a role for speech production skills as an endophenotype of dyslexia.
      Phonological processing predicted spelling, while language predicted text reading
      accuracy and comprehension. FRD was a significant additional predictor of reading
      and spelling after controlling for speech production, language and phonological
      processing, suggesting that children with FRD show additional difficulties in
      literacy that cannot be fully explained in terms of their language and
      phonological skills. 

PMID- 24581038
TI  - "Fourteen dollars for one beer!" Pre-drinking is associated with high-risk
      drinking among Victorian young adults.
AB  - OBJECTIVE: Pre-drinking entails consuming alcohol before attending licensed
      venues. We examined the relationship between pre-drinking, intention to get drunk
      and high-risk drinking among Victorians aged 18-24 years, to consider whether
      reducing pre-drinking might ameliorate alcohol-related harm. METHODS: Variables
      within the 2009 Victorian Youth Alcohol and Drugs Survey (VYADS) dataset were
      analysed and compared with a thematic interpretation of research interviews
      involving 60 young adults living in Melbourne. High-risk drinking was defined as
      consuming 11 or more standard drinks in a session at least monthly. RESULTS:
      VYADS data show that pre-drinking was a significant predictor of high-risk
      drinking, even after intention to get drunk was controlled for. The most common
      explanation provided by interviewees for pre-drinking was because it is cheaper
      to purchase alcohol at bottle shops than at bars and clubs. This was particularly
      emphasised by those who drank at a high-risk level. CONCLUSIONS: The study
      suggests that people pre-drink because they desire to be intoxicated, but also
      that pre-drinking patterns and product choices exacerbate the likelihood of high
      risk drinking. Reducing availability of cheap packaged alcohol has potential to
      limit both pre-drinking and high-risk drinking among Victorian young adults.
      IMPLICATIONS: The study adds weight to calls to implement minimum alcohol pricing
      in Australia.

PMID- 24581039
TI  - Assessment of identity disequilibrium and its relation to empirical
      heterozygosity fitness correlations: a meta-analysis.
AB  - Heterozygosity fitness correlations (HFCs) have frequently been used to detect
      inbreeding depression, under the assumption that genome-wide heterozygosity is a
      good proxy for inbreeding. However, meta-analyses of the association between
      fitness measures and individual heterozygosity have shown that often either no
      correlations are observed or the effect sizes are small. One of the reasons for
      this may be the absence of variance in inbreeding, a requisite for generating
      general-effect HFCs. Recent work has highlighted identity disequilibrium (ID) as
      a measure that may capture variance in the level of inbreeding within a
      population; however, no thorough assessment of ID in natural populations has been
      conducted. In this meta-analysis, we assess the magnitude of ID (as measured by
      the g2 statistic) from 50 previously published HFC studies and its relationship
      to the observed effect sizes of those studies. We then assess how much power the
      studies had to detect general-effect HFCs, and the number of markers that would
      have been needed to generate a high expected correlation (r(2) = 0.9) between
      observed heterozygosity and inbreeding. Across the majority of studies, g2 values
      were not significantly different than zero. Despite this, we found that the
      magnitude of g2 was associated with the average effect sizes observed in a
      population, even when point estimates were nonsignificant. These low values of g2
      translated into low expected correlations between heterozygosity and inbreeding
      and suggest that many more markers than typically used are needed to robustly
      detect HFCs.

PMID- 24581040
TI  - Progressive nodules on the right shin of a 74-year-old woman.

PMID- 24581042
TI  - Modular assembly of designer PUF proteins for specific post-transcriptional
      regulation of endogenous RNA.
AB  - BACKGROUND: Due to their modular repeat structure, Pumilio/fem-3 mRNA binding
      factor (PUF) proteins are promising candidates for designer RNA-binding protein
      (RBP) engineering. To further facilitate the application of the PUF domain for
      the sequence-specific RBP engineering, a rapid cloning approach is desirable that
      would allow efficient introduction of multiple key amino acid mutations in the
      protein. Here, we report the implementation of the Golden Gate cloning method for
      an efficient one-step assembly of a designer PUF domain for RNA specificity
      engineering. RESULTS: We created a repeat module library that is potentially
      capable of generating a PUF domain with any desired specificity. PUF domains with
      multiple repeat modifications for the recognition of altered RNA targets were
      obtained in a one-step assembly reaction, which was found to be highly efficient.
      The new PUF variants exhibited high in vitro binding efficiencies to cognate RNA
      sequences, corroborating the applicability of the modular approach for PUF
      engineering. To demonstrate the application of the PUF domain assembly method for
      RBP engineering, we fused the PUF domain to a post-transcriptional regulator and
      observed a sequence-specific reporter and endogenous gene repression in human
      cell lines. CONCLUSIONS: The Golden Gate based cloning approach thus should allow
      greater flexibility and speed in implementing the PUF protein scaffold for
      engineering designer RBPs, and facilitate its use as a tool in basic and applied
      biology and medicine.

PMID- 24581041
TI  - Characterisation of Caenorhabditis elegans sperm transcriptome and proteome.
AB  - BACKGROUND: Although sperm is transcriptionally and translationally quiescent,
      complex populations of RNAs, including mRNAs and non-coding RNAs, exist in sperm.
      Previous microarray analysis of germ cell mutants identified hundreds of sperm
      genes in Caenorhabditis elegans. To take a more comprehensive view on C. elegans
      sperm genes, here, we isolate highly pure sperm cells and employ high-throughput
      technologies to obtain sperm transcriptome and proteome. RESULTS: First, sperm
      transcriptome consists of considerable amounts of non-coding RNAs, many of which
      have not been annotated and may play functional roles during spermatogenesis.
      Second, apart from kinases/phosphatases as previously reported, ion binding
      proteins are also enriched in sperm, underlying the crucial roles of
      intracellular ions in post-translational regulation in sperm. Third, while the
      majority of sperm genes/proteins have low abundance, a small number of sperm
      genes/proteins are hugely enriched in sperm, implying that sperm only rely on a
      small set of proteins for post-translational regulation. Lastly, by extensive
      RNAi screening of sperm enriched genes, we identified a few genes that control
      fertility. Our further analysis reveals a tight correlation between sperm
      transcriptome and sperm small RNAome, suggesting that the endogenous siRNAs
      strongly repress sperm genes. This leads to an idea that the inefficient RNAi
      screening of sperm genes, a phenomenon currently with unknown causes, might
      result from the competition between the endogenous RNAi pathway and the exogenous
      RNAi pathway. CONCLUSIONS: Together, the obtained sperm transcriptome and
      proteome serve as valuable resources to systematically study spermatogenesis in
      C. elegans.

PMID- 24581043
TI  - Measuring satisfaction with health care in young persons with inflammatory bowel
      disease--an instrument development and validation study.
AB  - BACKGROUND: Patient satisfaction is a relevant prognostic factor in young persons
      with chronic disease and may be both age and disease specific. To assess health
      care quality from the patient's view in young persons with inflammatory bowel
      disease, an easy to use, valid, reliable and informative specific instrument was
      needed. METHODS: All parts of the study were directed at persons with
      inflammatory bowel disease aged 15 to 24 ("youth"). A qualitative internet
      patient survey was used to generate items, complemented by a physician survey and
      literature search. A 2nd internet survey served to reduce items based on
      perceived importance and representativeness. Following pilot testing to assess
      ease of use and face validity, 150 respondents to a postal survey in patients
      from a paediatric clinical registry were included for validation analyses.
      Construct validity was assessed by relating summary scores to results from global
      questions on satisfaction with care using ANOVA. To assess test-retest
      reliability using intraclass correlation coefficients (ICC), a subset of patients
      were assessed twice within 3 months. RESULTS: 302 persons with IBD and 55
      physicians participated in the item generating internet survey, resulting in
      3,954 statements. After discarding redundancies 256 statements were presented in
      the 2nd internet survey. Of these, 32 items were retained. The resulting
      instrument assesses both the perceived relevance (importance) of an item as well
      as the performance of the care giver for each item for calculation of a summary
      satisfaction score (range 0 to 1). Sensibility testing showed good acceptance for
      most items. Construct validity was good, with mean scores of 0.63 (0.50 to 0.76),
      0.71 (0.69 to 0.74) and 0.81 (0.79 to 0.83) for no, some and good global
      satisfaction (ANOVA, p < 0.001). Test-retest reliability was satisfactory (ICC
      0.6 to 0.7). CONCLUSIONS: We developed an easy to use, patient oriented, valid
      instrument to assess satisfaction with care in young persons with IBD for use in
      survey research.

PMID- 24581044
TI  - Evidence of cryptic and pseudocryptic speciation in the Paracalanus parvus
      species complex (Crustacea, Copepoda, Calanoida).
AB  - INTRODUCTION: Many marine planktonic crustaceans such as copepods have been
      considered as widespread organisms. However, the growing evidence for cryptic and
      pseudo-cryptic speciation has emphasized the need of re-evaluating the status of
      copepod species complexes in molecular and morphological studies to get a clearer
      picture about pelagic marine species as evolutionary units and their
      distributions. This study analyses the molecular diversity of the ecologically
      important Paracalanus parvus species complex. Its seven currently recognized
      species are abundant and also often dominant in marine coastal regions worldwide
      from temperate to tropical oceans. RESULTS: COI and Cytochrome b sequences of 160
      specimens of the Paracalanus parvus complex from all oceans were obtained.
      Furthermore, 42 COI sequences from GenBank were added for the genetic analyses.
      Thirteen distinct molecular operational taxonomic units (MOTU) and two single
      sequences were revealed with cladistic analyses (Maximum Likelihood, Bayesian
      Inference), of which seven were identical with results from species delimitation
      methods (barcode gaps, ABDG, GMYC, Rosenberg's P(AB)). In total, 10 to 12
      putative species were detected and could be placed in three categories: (1)
      temperate geographically isolated, (2) warm-temperate to tropical wider spread
      and (3) circumglobal warm-water species. CONCLUSIONS: The present study provides
      evidence of cryptic or pseudocryptic speciation in the Paracalanus parvus
      complex. One major insight is that the species Paracalanus parvus s.s. is not
      panmictic, but may be restricted in its distribution to the northeastern
      Atlantic.

PMID- 24581046
TI  - A procedure for the transient expression of genes by agroinfiltration above the
      permissive threshold to study temperature-sensitive processes in plant-pathogen
      interactions.
AB  - Localized expression of genes in plants from T-DNAs delivered into plant cells by
      Agrobacterium tumefaciens is an important tool in plant research. The technique,
      known as agroinfiltration, provides fast, efficient ways to transiently express
      or silence a desired gene without resorting to the time-consuming, challenging
      stable transformation of the host, the use of less efficient means of delivery,
      such as bombardment, or the use of viral vectors, which multiply and spread
      within the host causing physiological alterations themselves. A drawback of the
      agroinfiltration technique is its temperature dependence: early studies have
      shown that temperatures above 29  degrees C are nonpermissive to tumour induction
      by the bacterium as a result of failure in pilus formation. However, research in
      plant sciences is interested in studying processes at these temperatures, above
      the 25  degrees C experimental standard, common to many host-environment and host
      pathogen interactions in nature, and agroinfiltration is an excellent tool for
      this purpose. Here, we measured the efficiency of agroinfiltration for the
      expression of reporter genes in plants from T-DNAs at the nonpermissive
      temperature of 30  degrees C, either transiently or as part of viral amplicons,
      and envisaged procedures that allow and optimize its use for gene expression at
      this temperature. We applied this technical advance to assess the performance at
      30  degrees C of two viral suppressors of silencing in agropatch assays [Potato
      virus Y helper component proteinase (HCPro) and Cucumber mosaic virus 2b protein]
      and, within the context of infection by a Potato virus X (PVX) vector, also
      assessed indirectly their effect on the overall response of the host Nicotiana
      benthamiana to the virus. 

PMID- 24581045
TI  - Sex differences in a mouse model of multiple sclerosis: neuropathic pain behavior
      in females but not males and protection from neurological deficits during
      proestrus.
AB  - BACKGROUND: Multiple sclerosis (MS), a demyelinating disease of the central
      nervous system, is one of the most prevalent neurological disorders in the
      industrialized world. This disease afflicts more than two million people
      worldwide, over two thirds of which are women. MS is typically diagnosed between
      the ages of 20-40 and can produce debilitating neurological impairments including
      muscle spasticity, muscle paralysis, and chronic pain. Despite the large sex
      disparity in MS prevalence, clinical and basic research investigations of how sex
      and estrous cycle impact development, duration, and severity of neurological
      impairments and pain symptoms are limited. To help address these questions, we
      evaluated behavioral signs of sensory and motor functions in one of the most
      widely characterized animal models of MS, the experimental autoimmune
      encephalomyelitis (EAE) model. METHODS: C57BL/6 male and female mice received
      flank injection of complete Freund's adjuvant (CFA) or CFA plus myelin
      oligodendrocyte glycoprotein 35-55 (MOG35-55) to induce EAE. Experiment 1
      evaluated sex differences of EAE-induced neurological motor deficits and
      neuropathic pain-like behavior over 3 weeks, while experiment 2 evaluated the
      effect of estrous phase in female mice on the same behavioral measures for 3
      months. EAE-induced neurological motor deficits including gait analysis and
      forelimb grip strength were assessed. Neuropathic pain-like behaviors evaluated
      included sensitivity to mechanical, cold, and heat stimulations. Estrous cycle
      was determined daily via vaginal lavage. RESULTS: MOG35-55-induced EAE produced
      neurological impairments (i.e., motor dysfunction) including mild paralysis and
      decreases in grip strength in both females and males. MOG35-55 produced
      behavioral signs of neuropathic pain-mechanical and cold hypersensitivity-in
      females, but not males. MOG35-55 did not change cutaneous heat sensitivity in
      either sex. Administration of CFA or CFA + MOG35-55 prolonged the time spent in
      diestrus for 2 weeks, after which normal cycling returned. MOG35-55 produced
      fewer neurological motor deficits when mice were in proestrus relative to non
      proestrus phases. CONCLUSIONS: We conclude that female mice are superior to males
      for the study of neuropathic pain-like behaviors associated with MOG35-55-induced
      EAE. Further, proestrus may be protective against EAE-induced neurological
      deficits, thus necessitating further investigation into the impact that estrous
      cycle exerts on MS symptoms.

PMID- 24581048
TI  - Vertical p-type Cu-doped ZnO/n-type ZnO homojunction nanowire-based ultraviolet
      photodetector by the furnace system with hotwire assistance.
AB  - Vertical p-ZnO:Cu/n-ZnO homojunction nanowires (NWs) and whole ZnO:Cu NWs were
      synthesized on a ZnO thin film/glass substrate by a furnace at 600  degrees C
      with 1700  degrees C hotwire assistance. According to the ZnO:Cu NW
      investigation, the energy-dispersive X-ray (EDX) spectrum indicates that the Cu
      content is 3.01 atomic %. The X-ray diffraction (XRD) peaks of ZnO:Cu NWs shift
      toward larger angles with increasing amounts of doped Cu. The Cu dopant enhanced
      the photoluminescence (PL) green-band peak and decreased the conductivity of the
      NWs, as measured by I-V. The gas sensing measurement and Hall effect verified
      that all ZnO:Cu NWs were p-type. In this study, transmission electron microscopy
      (TEM) and EDX mapping images revealed that the majority of the Cu element is
      located at the top of the p-ZnO:Cu/n-ZnO NW. The high-resolution transmission
      electron microscopy (HRTEM) image of the p-ZnO:Cu region shows that the NWs are
      [0001] growth-oriented, with lateral surfaces enclosed by (1101) planes. The I-V
      curve of p-ZnO:Cu/n-ZnO NWs displays the characteristics of normal rectifying
      diodes. The photocurrent under ultraviolet (UV) exposure was around 6 times
      higher than the dark current at the reverse bias of -5 V. 

PMID- 24581047
TI  - Understanding the mapping between numerical approximation and number words:
      evidence from Williams syndrome and typical development.
AB  - All numerate humans have access to two systems of number representation: an exact
      system that is argued to be based on language and that supports formal
      mathematics, and an Approximate Number System (ANS) that is present at birth and
      appears independent of language. Here we examine the interaction between these
      two systems by comparing the profiles of people with Williams syndrome (WS) with
      those of typically developing children between ages 4 and 9 years. WS is a rare
      genetic deficit marked by fluent and well-structured language together with
      severe spatial deficits, deficits in formal math, and abnormalities of the
      parietal cortex, which is thought to subserve the ANS. One of our tasks,
      requiring approximate number comparison but no number words, revealed that the
      ANS precision of adolescents with WS was in the range of typically developing 2-
      to 4-year-olds. Their precision improved with age but never reached the level of
      typically developing 6- or 9-year-olds. The second task, requiring verbal number
      estimation using number words, revealed that the estimates produced by
      adolescents with WS were comparable to those of typically developing 6- and 9
      year-olds, i.e. were more advanced than their ANS precision. These results
      suggest that ANS precision is somewhat separable from the mapping between
      approximate numerosities and number words, as the former can be severely damaged
      in a genetic disorder without commensurate impairment in the latter. 

PMID- 24581049
TI  - Vaccination coverage of children aged 12-23 months in Gaziantep, Turkey:
      comparative results of two studies carried out by lot quality technique: what
      changed after family medicine?
AB  - BACKGROUND: Health care systems in many countries are changing for a variety of
      reasons. Monitoring of community-based services, especially vaccination coverage,
      is important during transition periods to ensure program effectiveness. In 2005,
      Turkey began a transformation from a "socialization of health services" system to
      a "family medicine" system. The family medicine system was implemented in the
      city of Gaziantep, in December, 2010. METHODS: Two descriptive, cross-sectional
      studies were conducted in Gaziantep city center; the first study was before the
      transition to the family medicine system and the second study was one year after
      the transition. The Lot Quality Technique methodology was used to determine the
      quality of vaccination services. The population studied was children aged 12-23
      months. Data from the two studies were compared in terms of vaccination coverage
      and lot service quality to determine whether there were any changes in these
      parameters after the transition to a family service system. RESULTS: A total of
      93.7% of children in Gaziantep were fully vaccinated before the transition.
      Vaccination rates decreased significantly to 84.0% (p<0.005) after the family
      medicine system was implemented. The number of unacceptable vaccine lots
      increased from 5 lots before the transition to 21 lots after the establishment of
      the family medicine system. CONCLUSIONS: The number of first doses of vaccine
      given was higher after family medicine was implemented; however, the numbers of
      second, third, and booster doses, and the number of children fully vaccinated
      were lower than before transition. Acceptable and unacceptable lots were not the
      same before and after the transition. Different health care personnel were
      employed at the lots after family medicine was implemented. This result suggests
      that individual characteristics of the health care personnel working in a
      geographic area are as important as the socioeconomic and cultural
      characteristics of the community.

PMID- 24581050
TI  - Study protocol: Munster tinnitus randomized controlled clinical trial-2013 based
      on tailor-made notched music training (TMNMT).
AB  - BACKGROUND: Tinnitus is a result of hyper-activity/hyper-synchrony of auditory
      neurons coding the tinnitus frequency, which has developed to synchronous mass
      activity owing the lack of inhibition. We assume that removal of exactly these
      frequency components from an auditory stimulus will cause the brain to reorganize
      around tonotopic regions coding the tinnitus frequency. Based on this assumption
      a novel treatment for tonal tinnitus - tailor-made notched music training (TMNMT)
      (Proc Natl Acad Sci USA 107:1207-1210, 2010; Ann N Y Acad Sci 1252:253-258, 2012;
      Frontiers Syst Neurosci 6:50, 2012) has been introduced and will be tested in
      this clinical trial on a large number of tinnitus patients. METHODS AND DESIGN: A
      randomized controlled trial (RCT) in parallel group design will be performed in a
      double-blinded manner. The choice of the intervention we are going to apply is
      based on two "proof of concept" studies in humans (Proc Natl Acad Sci USA
      107:1207-1210, 2010; Ann N Y Acad Sci 1252:253-258, 2012; Frontiers Syst Neurosci
      6:50, 2012; PloS One 6(9):e24685, 2011) and on a recent animal study (Front Syst
      Neurosci 7:21, 2013).The RCT includes 100 participants with chronic, tonal
      tinnitus who listened to tailor-made notched music (TMNM) for two hours a day for
      three months. The effect of TMNMT is assessed by the tinnitus handicap
      questionnaire and visual analogue scales (VAS) measuring perceived tinnitus
      loudness, distress and handicap. DISCUSSION: This is the first randomized
      controlled trial applying TMNMT on a larger number of patients with tonal
      tinnitus. Our data will verify more securely and reliably the effectiveness of
      this kind of completely non-invasive and low-cost treatment approach on tonal
      tinnitus. TRIAL REGISTRATION: Current Controlled Trials ISRCTN04840953.

PMID- 24581055
TI  - Term limits and the tobacco industry.
AB  - In the 1990s several American states passed term limits on legislators with the
      stated intention of reducing the influence of wealthy industries on career
      legislators. Although term limits in the United States do not have a direct
      relationship to public health, the tobacco industry anticipated that term limits
      could have indirect effects by either limiting or expanding industry influence.
      We detail the strategy of the tobacco industry in the wake of term limits using
      internal tobacco company documents and a database of campaign contributions made
      to legislators in term limited states between 1988 and 2002. Despite some
      expectations that term limits would limit tobacco industry access to state
      legislators, term limits appear to have had the opposite effect. 

PMID- 24581056
TI  - "I didn't think I could get out of the fucking park." Gay men's retrospective
      accounts of neighborhood space, emerging sexuality and migrations.
AB  - Young, African American and Latino gay, bisexual and other men who have sex with
      men (MSM) are disproportionately represented among new HIV cases according to the
      most recent national surveillance statistics. Analysts have noted that these
      racial/ethnic disparities in HIV among MSM exist within the wider context of
      sexual, mental and physical health disparities between MSM and heterosexuals. The
      intercorrelation of these adverse health outcomes among MSM, termed syndemics,
      has been theorized to be socially produced by a heterosexist social system that
      marginalizes lesbian, gay, bisexual, MSM and other sexual minorities. African
      American and Latino MSM experience overlapping systems of oppression that may
      increase their risk of experiencing syndemic health outcomes. In this paper,
      using data from twenty in-depth qualitative interviews with MSM living in four
      New York City (NYC) neighborhoods, we present accounts of neighborhood space,
      examining how space can both physically constitute and reinforce social systems
      of stratification and oppression, which in turn produce social disparities in
      sexual health outcomes. By analyzing accounts of emerging sexuality in
      neighborhood space, i.e. across time and space, we identify pathways to risk and
      contribute to our understanding of how neighborhood space is experienced by gay
      men, adding to our ability to support young men as they emerge in place and to
      shape the social topography of urban areas. 

PMID- 24581058
TI  - Relationships between the perceived neighborhood social environment and walking
      for transportation among older adults.
AB  - Ecological models state that physical activity (PA) behaviors can be explained by
      the interplay between individuals and their surrounding physical and social
      environment. However, the majority of research on PA-environment relationships
      has focused upon the physical environment. The purpose of the current study was
      to investigate the relationship between the perceived social environment and
      older adults' walking for transportation, while adjusting for individual and
      perceived physical environmental factors. Questionnaires were used to collect
      data on walking for transportation, individual, perceived physical and social
      environmental factors in 50,986 Flemish older adults (>=65 years) in the period
      of 2004-2010. Multilevel logistic regression analyses were applied to examine the
      relationships between perceived social environmental factors and the odds of
      daily walking for transportation. The final models showed significant positive
      relationships for frequency of contacts with neighbors, neighbors' social
      support, too many immigrants residing in the neighborhood, neighborhood
      involvement, participation, and volunteering. These results emphasize the need
      for including social environmental factors in future studies examining correlates
      of older adults' physical activity. Current findings suggest that projects
      stimulating interpersonal relationships, place attachment, and formal community
      engagement might promote walking for transportation among older adults. Future
      research should try to further disentangle the complex (inter)relationships and
      causal mechanisms between older individuals, their environments, and their
      walking for transportation behavior. 

PMID- 24581057
TI  - Childhood family psychosocial environment and carotid intima media thickness: the
      CARDIA study.
AB  - Little is known about whether the childhood family psychosocial environment
      (characterized by cold, unaffectionate interactions, conflict, aggression,
      neglect and/or low nurturance) affects coronary heart disease (CHD) risk.
      Objectives were to evaluate associations of childhood family psychosocial
      environment with carotid intima media thickness (IMT), a subclinical measure of
      atherosclerosis. The study population included 2659 CARDIA study participants,
      aged 37-52 years. Childhood family psychosocial environment was measured using a
      risky family questionnaire via self-report. Carotid IMT was calculated using the
      average of 20 measurements of mean common carotid, bulb and internal carotid IMT,
      assessed using high-resolution B-mode ultrasound images. Utilizing linear
      regression analyses adjusted for age, a 1-unit (range 0-21) increase in risky
      family score was associated with 0.0036 (95% CI: 0.0006,0.0066 mm) and 0.0020
      (95% CI: 0.0002,0.0038) mm increase in mean IMT in white males and females,
      respectively. Formal mediation analyses and covariate adjustments suggested
      childhood socioeconomic position and smoking may be important mechanisms in white
      males and females, as well as education and depressive symptomatology in white
      males. No associations were found in black participants. Formal statistical tests
      for interaction between risky family score and sex, and between risky family
      score and race/ethnicity, demonstrated borderline evidence of interactions for
      both sex (p = 0.12) and race/ethnicity (p = 0.14) with risky family score for
      associations with mean IMT. In conclusion, childhood family psychosocial
      environment was positively associated with IMT in white participants, with little
      evidence of association in black participants. Mechanisms in white participants
      may include potential negative impacts of socioeconomic constraints on parenting
      quality, potentially influencing offspring's cardiovascular risk factors (e.g.
      smoking), socioeconomic position (e.g. education), and/or psychosocial
      functioning (e.g. depression), which may in turn lead to atherosclerotic
      processes. Borderline racial/ethnic differences in findings should be replicated,
      but add to literature exploring race/ethnicity-specific associations of parenting
      approaches with health outcomes. 

PMID- 24581059
TI  - Comparing tailored and narrative worksite interventions at increasing colonoscopy
      adherence in adults 50-75: a randomized controlled trial.
AB  - Research has identified several communication strategies that could increase
      adherence to colorectal cancer screening recommendations. Two promising
      strategies are tailoring and narrative-based approaches. Tailoring is the
      personalization of information based on individual characteristics. Narrative
      based approaches use stories about similar others to counter perceived barriers
      and cultivate self-efficacy. To compare these two approaches, a randomized
      controlled trial was carried out at 8 worksites in Indiana. Adults 50-75 (N =
      209) received one of four messages about colorectal cancer screening: stock,
      narrative, tailored, tailored narrative. The primary outcome was whether
      participants filed a colonoscopy claim in the 18 months following the
      intervention. Individuals receiving narrative messages were 4 times more likely
      to screen than those not receiving narrative messages. Tailoring did not increase
      screening behavior overall. However, individuals with higher cancer information
      overload were 8 times more likely to screen if they received tailored messages.
      The results suggest that narrative-based approaches are more effective than
      tailoring at increasing colorectal cancer screening in worksite interventions.
      Tailoring may be valuable as a strategy for reaching individuals with high
      overload, perhaps as a follow-up effort to a larger communication campaign. 

PMID- 24581060
TI  - Of kin and kidneys: do kinship networks contribute to racial disparities in
      living donor kidney transplantation?
AB  - In the United States, racial disparities in kidney transplantation are large and
      especially stark for living donor transplants. Medical researchers frequently
      attribute this to the availability of medically compatible living kidney donors,
      who are usually kin. This paper evaluates this hypothesis by testing whether
      African American transplant candidates likely have lesser access to suitable
      living donors in their kinship networks than white candidates. This paper
      evaluates this hypothesis using a simulation design. Contrary to prior research
      on this topic, this simulation analysis concludes that black-white disparities in
      living donor kidney transplantation are unlikely to be the result of group
      differences in the availability of suitable donors. Although individual white kin
      are individually more likely to be suitable donors, African Americans' larger
      average kinship networks compensate for this difference. 

PMID- 24581061
TI  - Fast, cheap, and out of control? Speculations and ethical concerns in the conduct
      of outsourced clinical trials in India.
AB  - The globalization of biopharmaceutical clinical trials and their offshore
      outsourcing, from the West to low and middle-income countries, has come under
      increasing scrutiny from academic scholars, practitioners, regulatory agencies
      and the media. This article reports the results of a study conducted in Bangalore
      and Hyderabad between 2007 and 2009, to elicit the perspectives of stakeholders,
      concerning media representations of their work and the ethical issues that
      emanate from their engagement in the clinical trials enterprise. In acknowledging
      the inherently problematic nature of the outsourcing of clinical trials to low
      income countries, I argue that the practice of not prioritizing research on
      diseases that are most prevalent among communities, from which subjects are
      recruited, demands a coordinated and sustained critique. I propose that the
      critical discourse on the outsourcing of clinical trials should not only
      emphasize the perils of this practice, but also address some broader issues of
      equity and distributive justice that determine people's access to basic health
      care in low income countries. Close attention to the specific context of clinical
      trials in an increasingly neoliberal medical and health environment in emerging
      economies such as India can provide critical insights into the on-the-ground
      complexities and challenges of outsourced global clinical trials. 

PMID- 24581062
TI  - Why don't clinicians adhere more consistently to guidelines for the Integrated
      Management of Childhood Illness (IMCI)?
AB  - The Integrated Management of Childhood Illness (IMCI) has been introduced to
      reduce child morbidity and mortality in countries with a poor health
      infrastructure. Previous studies have documented a poor adherence to clinical
      guidelines, but little is known about the reasons for non-adherence. This mixed
      method study measures adherence to IMCI case-assessment guidelines and identifies
      the reasons for weak adherence. In 2007, adherence was measured through direct
      observation of 933 outpatient consultations performed by 103 trained clinicians
      in 82 health facilities in nine districts in rural Tanzania, while clinicians'
      knowledge of the guidelines was assessed through clinical vignettes. Other
      potential reasons for a weak adherence were assessed through both a health worker
      and health facility survey, as well as by a qualitative follow-up study in 2009
      in which in-depth interviews were conducted with 40 clinicians in 30 health
      facilities located in two of the same districts. Clinicians performed 28.4% of
      the relevant IMCI assessment tasks. The level of knowledge was considerably
      higher than actual performance, suggesting that lack of knowledge is not the only
      constraint for improved performance. Other important reasons for weak performance
      seem to be 1) lack of motivation to adhere to IMCI guidelines, stemming partly
      from a weak belief in the importance of following the guidelines and partly from
      weak intrinsic motivation, and 2) a physical and/or cognitive "overload",
      resulting in lack of capacity to concentrate fully on each and every case and a
      resort to simpler rules of thumb. Poor remunerations contribute to several of
      these factors. 

PMID- 24581064
TI  - Food and nutrition security public initiatives from a human and socioeconomic
      development perspective: mapping experiences within the 1996 World Food Summit
      signatories.
AB  - Food security exists when all people, at all times, have physical and economic
      access to sufficient, safe and nutritious food to meet their dietary needs and
      food preferences for an active and healthy life. In a global scenario where
      hunger and obesity affect millions of people, public actions have been developed
      towards Food and Nutrition Security (FNS). In 1996 during the World Food Summit,
      186 countries signed the Rome Declaration, committing themselves to assess and
      address Food and Nutrition Insecurity. In this exploratory study, we compile
      secondary internet data using keywords in four languages to map the global
      distribution, among signatories, of FNS public initiatives and assess their
      association with key national-level socioeconomic indicators. As a result, we
      found FNS public policies in 123 countries, reports on the state of FNS in 139
      countries, and the presence of both in 114 countries (61%). The proportion of
      countries with any type of, as well as with specific, FNS policy or diagnostic
      was higher in least developed countries. There was a statistically significant
      association between these proportions and selected national-level socioeconomic
      variables. The results are discussed along with population vulnerability,
      international cooperation mechanisms and political discourse and how these
      factors impact the existence of FNS public actions. 

PMID- 24581063
TI  - The pathways from perceived discrimination to self-rated health: an investigation
      of the roles of distrust, social capital, and health behaviors.
AB  - Although there has been extensive research on the adverse impacts of perceived
      discrimination on health, it remains unclear how perceived discrimination gets
      under the skin. This paper develops a comprehensive structural equation model
      (SEM) by incorporating both the direct effects of perceived discrimination on
      self-rated health (SRH), a powerful predictor for many health outcomes, and the
      indirect effects of perceived discrimination on SRH through health care system
      distrust, neighborhood social capital, and health behaviors and health
      conditions. Applying SEM to 9880 adults (aged between 18 and 100) in the 2008
      Southeastern Pennsylvania Household Health Survey, we not only confirmed the
      positive and direct association between discrimination and poor or fair SRH, but
      also verified two underlying mechanisms: 1) perceived discrimination is
      associated with lower neighborhood social capital, which further contributes to
      poor or fair SRH; and 2) perceived discrimination is related to risky behaviors
      (e.g., reduced physical activity and sleep quality, and intensified smoking) that
      lead to worse health conditions, and then result in poor or fair SRH. Moreover,
      we found that perceived discrimination is negatively associated with health care
      system distrust, but did not find a significant relationship between distrust and
      poor or fair SRH. 

PMID- 24581065
TI  - Rewarding altruism: addressing the issue of payments for volunteers in public
      health initiatives.
AB  - Lay involvement in public health programmes occurs through formalised lay health
      worker (LHW) and other volunteer roles. Whether such participation should be
      supported, or indeed rewarded, by payment is a critical question. With reference
      to policy in England, UK, this paper argues how framing citizen involvement in
      health only as time freely given does not account for the complexities of
      practice, nor intrinsic motivations. The paper reports results on payment drawn
      from a study of approaches to support lay people in public health roles,
      conducted in England, 2007-9. The first phase of the study comprised a scoping
      review of 224 publications, three public hearings and a register of projects.
      Findings revealed the diversity of approaches to payment, but also the contested
      nature of the topic. The second phase investigated programme support matters in
      five case studies of public health projects, which were selected primarily to
      reflect role types. All five projects involved volunteers, with two utilising
      forms of payment to support engagement. Interviews were conducted with a sample
      of project staff, LHWs (paid and unpaid), external partners and service users.
      Drawing on both lay and professional perspectives, the paper explores how payment
      relates to social context as well as various motivations for giving, receiving or
      declining financial support. The findings show that personal costs are not always
      absorbed, and that there is a potential conflict between financial support,
      whether sessional payment or expenses, and welfare benefits. In identifying some
      of the advantages and disadvantages of payment, the paper highlights the
      complexity of an issue often addressed only superficially. It concludes that, in
      order to support citizen involvement, fairness and value should be considered
      alongside pragmatic matters of programme management; however policy conflicts
      need to be resolved to ensure that employment and welfare rights are maintained. 

PMID- 24581066
TI  - How is post-industrial decline associated with the geography of physical
      activity? Evidence from the Health Survey for England.
AB  - In recent decades, the prevalence of physical activity has declined considerably
      in many developed countries, which has been related to rising levels of obesity
      and several weight-related medical conditions, such as coronary heart disease.
      There is evidence that areas exhibiting particularly low levels of physical
      activity have undergone a strong transition away from employment in physically
      demanding occupations. It is proposed that such processes of deindustrialisation
      may be causally linked to unexplained geographical disparities in physical
      activity. This study investigates how geographical variations in
      deindustrialisation are associated with current levels of physical activity
      across different activity domains and relevant macro-economic time periods in
      England. The analysis includes data on 27,414 adults from the Health Survey for
      England 2006 and 2008 who reported total, occupational, domestic, recreational
      and walking activity. Based on employment change in industries associated with
      heavy manual work, a local measurement of industrial decline was developed,
      covering the period 1841-2001. We applied a multilevel modelling approach to
      study associations between industrial decline and physical activity. Results
      indicate that the process of deindustrialisation appears to be associated with
      patterns of physical activity and that this is independent of household income.
      The effects observed were generally similar for men and women. However, the
      nature of the association differed across areas, time periods and employment
      types; in particular, residents of districts characterised by a history of
      manufacturing and mining employment had increased odds of reporting low activity
      levels. We conclude that post-industrial change may be a factor in explaining
      present-day variations in physical activity, emphasising the plausible impact of
      inherited cultures and regional identities on health related behaviours. 

PMID- 24581067
TI  - What determines providers' stated preference for the treatment of uncomplicated
      malaria?
AB  - As agents for their patients, providers often make treatment decisions on behalf
      of patients, and their choices can affect health outcomes. However, providers
      operate within a network of relationships and are agents not only for their
      patients, but also other health sector actors, such as their employer, the
      Ministry of Health, and pharmaceutical suppliers. Providers' stated preferences
      for the treatment of uncomplicated malaria were examined to determine what
      factors predict their choice of treatment in the absence of information and
      institutional constraints, such as the stock of medicines or the patient's
      ability to pay. 518 providers working at non-profit health facilities and for
      profit pharmacies and drug stores in Yaounde and Bamenda in Cameroon and in Enugu
      State in Nigeria were surveyed between July and December 2009 to elicit the
      antimalarial they prefer to supply for uncomplicated malaria. Multilevel
      modelling was used to determine the effect of financial and non-financial
      incentives on their preference, while controlling for information and
      institutional constraints, and accounting for the clustering of providers within
      facilities and geographic areas. 69% of providers stated a preference for
      artemisinin-combination therapy (ACT), which is the recommended treatment for
      uncomplicated malaria in Cameroon and Nigeria. A preference for ACT was
      significantly associated with working at a for-profit facility, reporting that
      patients prefer ACT, and working at facilities that obtain antimalarials from
      drug company representatives. Preferences were similar among colleagues within a
      facility, and among providers working in the same locality. Knowing the
      government recommends ACT was a significant predictor, though having access to
      clinical guidelines was not sufficient. Providers are agents serving multiple
      principals and their preferences over alternative antimalarials were influenced
      by patients, drug company representatives, and other providers working at the
      same facility and in the local area. Efforts to disseminate drug policy should
      target the full range of actors involved in supplying drugs, including providers,
      employers, suppliers and local communities. 

PMID- 24581068
TI  - Youth physical activity and the neighbourhood environment: examining correlates
      and the role of neighbourhood definition.
AB  - The primary objective of this study was to examine relationships between
      neighbourhood built and social environment characteristics and moderate to
      vigorous physical activity (MVPA) in a sample of children aged 8-11 in Vancouver,
      British Columbia and the surrounding lower mainland region (n = 366). A secondary
      objective was to assess how neighbourhood definition influences these
      relationships, by using measures calculated at multiple buffer sizes: 200, 400,
      800 and 1600 m (1 mile). Geographic information systems -software was used to
      create a broad set of measures of neighbourhood environments. Physical activity
      was measured objectively using accelerometers. Relationships between MVPA and
      neighborhood characteristics were assessed using generalized estimating equations
      to account for the clustering of children within schools. Sex specific
      relationships were assessed through sex stratified models. When controlling for
      child age, sex and ethnicity, MVPA was positively associated with commercial
      density, residential density, number of parks and intersection density; and
      negatively associated with distance to school and recreation sites. When entered
      as a composite index, these measures accounted for 4.4% in the variation in MVPA
      for the full sample (boys and girls). Sex stratified models better explained the
      relationships between neighbourhood environment and physical activity. For boys,
      built and social environment characteristics of neighbourhoods accounted for 8.7%
      of the variation in MVPA, and for girls, neighborhood factors explained 7.2% of
      the variation. Sex stratified models also point towards distinct differences in
      factors associated with physical activity, with MVPA of boys associated with
      wider ranging neighborhood characteristics than MVPA of girls. For girls, two
      safety-related neighbourhood features were found to be significantly associated
      with MVPA: cul-de-sac density and proportion of low speed limit streets. In all
      models, larger buffer sizes, and predominantly the largest buffer size, best
      explained environment-physical activity relationships. 

PMID- 24581069
TI  - Constructing a trial as a personal lifestyle change project: participants'
      experiences in a clinical study for nicotine vaccination.
AB  - The purpose of this study was to gain insight into the experiences and dynamics
      of the involvement of research participants in a randomized clinical trial for
      nicotine vaccination. Participants received an experimental nicotine vaccine or a
      placebo, in addition to quit smoking medication and counseling. The longitudinal
      design of this qualitative study allowed us to follow people from their first
      visit to the trial location until the unblinding of their treatment with either
      verum or placebo vaccine. The empirical data consisted of 49 semi-structured, in
      depth interviews, field notes and memos, and trial documents collected in the
      Netherlands between 2010 and 2012. Participants' expectations and experiences of
      the innovative nicotine vaccine were characterized by ambivalence: Although they
      complied with the research design, throughout the study they tinkered with
      discourses, objects, and activities to make them serve their individual goals.
      They made the concepts of nicotine vaccination and placebo treatment meaningful
      for quitting, reshaped the meaning of research tests and obligatory visits to
      serve their own personal goals, and introduced a new element into the trial by
      creating space to discuss problems that might endanger the quit attempt. In
      short, the participants constructed the clinical study for nicotine vaccination
      as their own personal lifestyle change project. 

PMID- 24581070
TI  - Adolescents' perceptions of health from disadvantaged urban communities: findings
      from the WAVE study.
AB  - The Well-being of Adolescents in Vulnerable Environments (WAVE) is a global study
      of young people living in disadvantaged urban communities from Baltimore, MD,
      Johannesburg, South Africa, Shanghai, China, New Delhi, India and Ibadan,
      Nigeria. WAVE was launched in the summer of 2011 to: 1) explore adolescents'
      perceived health and their top health challenges; and 2) describe the factors
      that adolescents perceive to be related to their health and health care
      utilization. Researchers in each site conducted in-depth interviews among
      adolescents; community mapping and focus groups among adolescents; a Photovoice
      methodology, in which adolescents were trained in photography and took photos of
      the meaning of 'health' in their communities; and key informant interviews among
      adults who work with young people. A total 529 participants from across the sites
      were included in the analysis. Findings from the study showed that gender played
      a large role with regards to what adolescents considered as their top health
      challenges. Among females, sexual and reproductive health problems were primary
      health challenges, whereas among males, tobacco, drug, and alcohol consumption
      was of highest concern, which often resulted into acts of violence. Personal
      safety was also a top concern among males and females from Baltimore and
      Johannesburg, and among females in New Delhi and Ibadan. Factors perceived to
      influence health the most were the physical environment, which was characterized
      by inadequate sanitation and over-crowded buildings, and the social environment,
      which varied in influence by gender and site. Regardless of the study site,
      adolescents did not consider physical health as a top priority and very few felt
      the need to seek health care services. This study highlights the need to focus on
      underlying structural and social factors for promoting health and well-being
      among adolescents in disadvantaged urban environments. 

PMID- 24581071
TI  - Does childhood misfortune raise the risk of acute myocardial infarction in
      adulthood?
AB  - Whereas most research on acute myocardial infarction (AMI) has focused on more
      proximal influences, such as adult health behaviors, the present study examines
      the early origins of AMI. Longitudinal data were drawn from the National Survey
      of Midlife Development in the United States (N = 3032), a nationally
      representative survey of men and women aged 25-74, which spans from 1995 to 2005.
      A series of event history analyses modeling age of first AMI investigated the
      direct effects of accumulated and separate domains of childhood misfortune as
      well as the mediating effects of adult health lifestyle and psychosocial factors.
      Findings reveal that accumulated childhood misfortune and child maltreatment
      increased AMI risk, net of several adult covariates, including family history of
      AMI. Smoking fully mediated the effects of both accumulated childhood misfortune
      and child maltreatment. These findings reveal the importance of the early origins
      of AMI and health behaviors as mediating factors. 

PMID- 24581072
TI  - Contextual determinants of US nursing home racial/ethnic diversity.
AB  - We hypothesized that for-profit/chain affiliated nursing homes, those in states
      with higher Medicaid reimbursement, and those in more competitive markets would
      have greater resident racial/ethnic diversity than nursing homes not meeting
      these criteria. Using 2004 Online Survey, Certification and Reporting data,
      Minimum Data Set, Lewis Mumford Center for Comparative Urban and Regional
      Research data, and the Area Resource File, we included U.S. Medicare/Medicaid
      certified nursing homes (N = 8950) located in 310 Metropolitan Statistical Areas.
      The dependent variable quantified facility-level multiracial diversity. Ordinary
      least squares regression showed support for the hypothesized relationships: for
      profit/chain affiliated nursing homes were more diverse than nursing homes in all
      other ownership/chain member categories, while higher Medicaid per-diem rates,
      greater residential diversity, and stronger market competition were also
      positively associated with nursing home racial/ethnic composition. Results
      suggest there is room for policy changes to achieve equitable access to all
      levels of nursing home services for minority elders. 

PMID- 24581073
TI  - The role of social capital in African-American women's use of mammography.
AB  - Black/African-American women are more likely to get breast cancer at a young age
      and/or be diagnosed at a late disease stage, pointing to a greater need to
      promote mammography for Black women at earlier ages than are currently
      recommended. This study explores how perceived neighborhood social capital, that
      is, perceptions of how tight-knit a neighborhood is and what power that confers
      to neighborhood members, relates to use of mammography for Black women in
      Philadelphia. Living in a community with tight social ties (social cohesion) or
      that have a collective motivation for community change (collective efficacy) may
      increase the likelihood that an individual woman in that community will hear
      health messages from other community members and neighbors (diffusion of
      information) and will have access to health-related resources that allow them to
      engage in healthy behaviors. No prior studies have explored the role of social
      capital in decisions for mammography use. Using multilevel logistic regression,
      we analyzed self-report of mammography in the past year for 2586, Black women
      over age 40 across 381 Philadelphia, Pennsylvania USA census tracts. Our study
      included individual demographic and aggregates of individual-level social capital
      data from the Public Health Management Corporation's 2004, 2006, and 2008
      Community Health Database waves, and 2000 US Census sociodemographic
      characteristics. Individual perceptions that a Black woman's neighborhood had
      high social capital, specifically collective efficacy, had a positive and
      statistically significant association with mammography use (OR = 1.40, CI: 1.05,
      1.85). Our findings suggest that an individual woman's perception of greater
      neighborhood social capital may be related to increased mammography use. Although
      this analysis could not determine the direction of causality, it suggests that
      social capital may play a role in cancer preventive screening for African
      American women in Philadelphia, which warrants further study. 

PMID- 24581074
TI  - Institutional ethical review and ethnographic research involving injection drug
      users: a case study.
AB  - Ethnographic research among people who inject drugs (PWID) involves complex
      ethical issues. While ethical review frameworks have been critiqued by social
      scientists, there is a lack of social science research examining institutional
      ethical review processes, particularly in relation to ethnographic work. This
      case study describes the institutional ethical review of an ethnographic research
      project using observational fieldwork and in-depth interviews to examine
      injection drug use. The review process and the salient concerns of the review
      committee are recounted, and the investigators' responses to the committee's
      concerns and requests are described to illustrate how key issues were resolved.
      The review committee expressed concerns regarding researcher safety when
      conducting fieldwork, and the investigators were asked to liaise with the police
      regarding the proposed research. An ongoing dialogue with the institutional
      review committee regarding researcher safety and autonomy from police
      involvement, as well as formal consultation with a local drug user group and
      solicitation of opinions from external experts, helped to resolve these issues.
      This case study suggests that ethical review processes can be particularly
      challenging for ethnographic projects focused on illegal behaviours, and that
      while some challenges could be mediated by modifying existing ethical review
      procedures, there is a need for legislation that provides legal protection of
      research data and participant confidentiality. 

PMID- 24581076
TI  - Talking with text: communication in therapist-led, live chat cancer support
      groups.
AB  - CancerChatCanada is a pan-Canadian initiative with a mandate to make
      professionally led cancer support groups available to more people in Canada.
      Although online support groups are becoming increasingly popular, little is known
      about therapist-led, synchronous groups using live chat. The purpose of this
      study was to generate a rich descriptive account of communication experiences in
      CancerChatCanada groups and to gain an understanding of processes associated with
      previously-reported benefits. We used interpretive description to analyze
      interview segments from 102 patients, survivors and family caregivers who
      participated in CancerChatCanada groups between 2007 and 2011. The analysis
      yielded four inter-related process themes (Reaching Out From Home, Feeling Safe,
      Emotional Release, and Talking With Text) and one outcome theme (Resonance and
      Kinship). The findings extend previous research about text-only online support
      groups and provide novel insights into features of facilitated, live chat
      communication that are valued by group members. 

PMID- 24581077
TI  - Macroeconomic fluctuations and motorcycle fatalities in the U.S.
AB  - The effects of business cycles on health outcomes in general, and on traffic
      fatalities in particular, have received much attention recently. In this paper,
      we focus on motorcycle safety and examine the impact of changing levels of
      economic activity on fatal crashes by motorcyclists in the United States. We
      analyze state-level longitudinal data with 1,104 state/year observations from the
      1988-2010 Fatality Analysis Reporting System (FARS). Using the extensive
      motorcycle crash characteristics available in FARS, we examine not only total
      fatality rates but also rates decomposed by crash type, day, time, and the level
      of the motorcycle operator's blood alcohol content. Our results are consistent
      with much of the existing literature showing that traffic fatality rates are pro
      cyclical. The estimates suggest that a 10% increase in real income per capita is
      associated with a 10.4% rise in the total motorcycle fatality rate. Along with
      potential mechanisms, policymakers and public health officials should consider
      the effects of business cycles on motorcycle safety. 

PMID- 24581075
TI  - Racial disparities in self-rated health: trends, explanatory factors, and the
      changing role of socio-demographics.
AB  - This paper uses data from the U.S. National Health Interview Surveys (N =
      1,513,097) to describe and explain temporal patterns in black-white health
      disparities with models that simultaneously consider the unique effects of age,
      period, and cohort. First, we employ cross-classified random effects age-period
      cohort (APC) models to document black-white disparities in self-rated health
      across temporal dimensions. Second, we use decomposition techniques to shed light
      on the extent to which socio-economic shifts in cohort composition explain the
      age and period adjusted racial health disparities across successive birth
      cohorts. Third, we examine the extent to which exogenous conditions at the time
      of birth help explain the racial disparities across successive cohorts. Results
      show that black-white disparities are wider among the pre-1935 cohorts for women,
      falling thereafter; disparities for men exhibit a similar pattern but exhibit
      narrowing among cohorts born earlier in the century. Differences in socioeconomic
      composition consistently contribute to racial health disparities across cohorts;
      notably, marital status differences by race emerge as an increasingly important
      explanatory factor in more recent cohorts for women whereas employment
      differences by race emerge as increasingly salient in more recent cohorts for
      men. Finally, our cohort characteristics models suggest that cohort economic
      conditions at the time of birth (percent large family, farm or Southern birth)
      help explain racial disparities in health for both men and women. 

PMID- 24581078
TI  - Parenting with bipolar disorder: coping with risk of mood disorders to children.
AB  - Children of individuals with bipolar disorder (BPD) have increased risk for mood
      disorders and other adverse psychosocial outcomes due to genetic and
      environmental risk. Though parents with BPD are aware of increased risk to
      children, little is known about efforts undertaken in response or their perceived
      utility. Among parents who self-report with BPD, this study identifies key
      variables associated with parental coping with children's risk of mood disorders;
      and explores the relationship between monitoring children's moods and perceived
      coping efficacy. In this U.S. study, active parental coping with, and cognitive
      distancing from, child's risk were measured using novel scales. Parents (n = 266)
      who self-identified as having BPD completed a web-based survey. They had at least
      one unaffected child. Most participants endorsed monitoring their children's
      moods. Monitoring was associated with increased perceived control over the
      child's well-being (p < 0.005), but not feeling less worried. Active parental
      coping with risk to children was positively associated with active coping with
      own illness (beta = 0.25, p = 0.001), family history (beta = 0.24, p = 0.001),
      and self-report of current depression (beta = 0.16, p = 0.037), explaining 13.8%
      of the variance (F = 8.81, p < 0.001). Cognitive distancing from the child's risk
      was positively associated with confidence in diagnosis (beta = 0.25, p = 0.001),
      and negatively associated with self-report of current mania (beta = -0.19, p =
      0.007), perceiving BPD as genetic (beta = -0.26, p < 0.001) and having more
      children (beta = -0.20, p = 0.004); explaining 16.2% of the variance (F = 8.63, p
      < 0.001). Parents' adaptation to their own BPD was modestly correlated with
      active coping with child's risk (r = 0.15, p < 0.05) but not with cognitive
      distancing. The findings support the importance of understanding causal
      attributions and the value of genetic education and counseling for parents with
      BPD. Further research is necessary to elucidate the psychological benefits of
      active coping versus cognitive distancing from child's risk, and explore
      additional variables that predict parental coping with children's risk of mood
      disorders. 

PMID- 24581079
TI  - Health inequalities in Japan: the role of material, psychosocial, social
      relational and behavioural factors.
AB  - The extent that risk factors, identified in Western countries, account for health
      inequalities in Japan remains unclear. We analysed a nationally representative
      sample (Comprehensive Survey of Living Conditions surveyed in 2001 (n = 40,243)).
      The cross-sectional association between self-rated fair or poor health and
      household income and a theory-based occupational social class was summarised
      using the relative index of inequality [RII]. The percentage attenuation in RII
      accounted for by candidate contributory factors - material, psychosocial, social
      relational and behavioural - was computed. The results showed that the RII for
      household income based on self-rated fair or poor health was reduced after
      including the four candidate contributory factors in the model by 20% (95% CI
      2.1, 43.6) and 44% (95% CI 18.2, 92.5) in men and women, respectively. The RII
      for the Japanese Socioeconomic Classification [J-SEC] was reduced, not
      significantly, by 22% (95% CI -6.3, 100.0) in men in the corresponding model,
      while J-SEC was not associated with self-rated health in women. Material factors
      produced the most consistent and strong attenuation in RII for both socioeconomic
      indicators, while the contributions attributable to behaviour alone were modest.
      Social relational factors consistently attenuated the RII for both socioeconomic
      indicators in men whereas they did not make an independent contribution in women.
      The influence of perceived stress was inconsistent and depended on the
      socioeconomic indicator used. In summary, social inequalities in self-rated fair
      or poor health were reduced to a degree by the factors included. The results
      indicate that the levelling of health across the socioeconomic hierarchy needs to
      consider a wide range of factors, including material and psychosocial factors, in
      addition to the behavioural factors upon which the current public health policies
      in Japan focus. The analyses in this study need to be replicated using a
      longitudinal study design to confirm the roles of different factors in health
      inequalities. 

PMID- 24581080
TI  - Choose and Book: a sociological analysis of 'resistance' to an expert system.
AB  - In 2004, the English Department of Health introduced a technology (Choose and
      Book) designed to help general practitioners and patients book hospital
      outpatient appointments. It was anticipated that remote booking would become
      standard practice once technical challenges were overcome. But despite political
      pressure and financial incentives, Choose and Book remained unpopular and was
      generally used reluctantly if at all. Policymakers framed this as a problem of
      'clinician resistance'. We considered Choose and Book from a sociological
      perspective. Our dataset, drawn from a qualitative study of computer use in
      general practice, comprised background documents, field notes, interviews,
      clinical consultations (directly observed and videotaped) and naturally occurring
      talk relating to referral to hospital in four general practices. We used strong
      structuration theory, Giddens' conceptualisation of expert systems, and
      sensitivity to other sociological perspectives on technology, institutions and
      professional values to examine the relationship between the external environment,
      the evolving technology and actions of human agents (GPs, administrators,
      managers and patients). Choose and Book had the characteristics of an expert
      system. It served to 'empty out' the content of the consultation as the abstract
      knowledge it contained was assumed to have universal validity and to over-ride
      the clinician's application of local knowledge and practical wisdom. Sick
      patients were incorrectly assumed to behave as rational choosers, able and
      willing to decide between potential options using abstracted codified
      information. Our analysis revealed four foci of resistance: to the policy of
      choice that Choose and Book symbolised and purported to deliver; to accommodating
      the technology's socio-material constraints; to interference with doctors'
      contextual judgements; and to adjusting to the altered social relations
      consequent on its use. We conclude that 'resistance' is a complex phenomenon with
      socio-material and normative components; it is unlikely to be overcome using the
      behaviourist techniques recommended in some health informatics and policy
      literature. 

PMID- 24581081
TI  - Violence as a public health problem: an ecological study of 169 countries.
AB  - Individual level risk factors for violence have been widely studied, but little
      is known about country-level determinants, particularly in low and middle-income
      countries. We hypothesized that income inequality, through its detrimental
      effects on social cohesion, would be related to an increase in violence
      worldwide, and in low and middle-income countries in particular. We examined
      country-level associations of violence with socio-economic and health-related
      factors, using crime statistics from the United Nations Office on Drugs and
      Crime, and indicators from the Human Development Report published by the United
      Nations Development Programme. Using regression models, we measured relationships
      between country-level factors (age, education, measures of income, health
      expenditure, and alcohol consumption) and four violent outcomes (including
      measures of violence-related mortality and morbidity) in up to 169 countries. We
      stratified our analyses comparing high with low and middle-income countries, and
      analysed longitudinal data on homicide and income inequality in high-income
      countries. In low and middle-income countries, income inequality was related to
      homicide, robbery, and self-reported assault (all p's < 0.05). In high-income
      countries, urbanicity was significantly associated with official assault (p =
      0.002, beta = 0.716) and robbery (p = 0.011, beta = 0.587) rates; income
      inequality was related to homicide (p = 0.006, beta = 0.670) and self-reported
      assault (p = 0.020, beta = 0.563), and longitudinally with homicide (p = 0.021).
      Worldwide, alcohol consumption was associated with self-reported assault rates (p
      < 0.001, beta = 0.369) suggesting public policy interventions reducing alcohol
      consumption may contribute to reducing violence rates. Our main finding was that
      income inequality was related to violence in low and middle-income countries.
      Public health should advocate for global action to moderate income inequality to
      reduce the global health burden of violence. 

PMID- 24581082
TI  - Prognostic significance of XB130 expression in surgically resected pancreatic
      ductal adenocarcinoma.
AB  - BACKGROUND: XB130 is a newly discovered adaptor protein for intracellular signal
      transduction; it is involved in gene regulation, cell proliferation, cell
      survival, cell migration, and tumorigenesis. However, its expression and role in
      pancreatic ductal adenocarcinoma (PDAC) have not been investigated. The present
      study was designed to clarify the prognostic significance of XB130 expression in
      PDAC. METHODS: A total of 76 consecutive patients with surgically resected PDAC
      were retrospectively reviewed. XB130 expression was detected by
      immunohistochemical analysis on the paraffin-embedded tumour sections.
      Correlation between the expression of XB130 and clinicopathological parameters
      was analyzed. RESULTS: XB130 expression was significantly upregulated in
      PDAC(56.5%, 43/76) compared to normal pancreas (0%, 0/15; P < 0.05). Increased
      XB130 expression was correlated with lymph node metastasis (P = 0.017), distant
      metastasis (P = 0.0024), high tumour-node-metastasis (TNM) stage (P =0.001), and
      high tumour grade (P = 0.013). The survival of 43 patients with high XB130
      expression was significantly worse than that of the 33 patients with low XB130
      expression (P = 0.001). Univariate analysis showed that high XB130 expression (P
      = 0.0045), tumour size (P = 0.024), distant metastasis (P = 0.003), TNM stage (P
      = 0.002) and lymphatic metastasis (P = 0.016) were independent prognostic factors
      of postoperative survival. Multivariate analysis using the Cox proportional
      hazards model showed that high XB130 expression and distant metastasis (P =
      0.0239) were significant independent risk factors. CONCLUSIONS: XB130 was
      overexpressed in the PDAC. XB130 is a promising pathological marker for the
      prediction of outcome in patients with PDAC.

PMID- 24581083
TI  - 4D CT and lung cancer surgical resectability: a technical innovation.
AB  - A 74-year-old man presents with a left upper lobe lung adenocarcinoma, which
      demonstrated a wide base intimately with the aortic arch. We utilised 4D CT
      technique with a wide field of view CT unit to preoperatively determine likely
      surgical resectability. We propose that 4D CT may be of use in further
      investigating lung cancer with likely invasion of adjacent structures. 

PMID- 24581084
TI  - Mean platelet volume as an inflammation marker in active pulmonary tuberculosis.
AB  - BACKGROUND: The mean platelet volume (MPV) reflects the size of platelets. It has
      been shown to be inversely correlated with level of the inflammation in some
      chronic inflammatory diseases. This prospective study aims to show the usability
      of MPV as an inflammation marker in patients with active pulmonary tuberculosis
      (PTB) by comparison with healthy controls. In addition, its relationships with
      other inflammatory markers such as C-reactive protein (CRP) and the erythrocyte
      sedimentation rate (ESR) as well as with the radiological extent of disease were
      examined. METHODS: This study included 82 patients with active PTB and 95 healthy
      subjects (control group). Whole blood counts, CRP level, and ESR were compared
      between the two groups. In the PTB group, the relationships between the
      radiological extent of disease and the MPV and other inflammation markers were
      investigated. RESULTS: The MPV was 7.74 +/- 1.33/MUL in the PTB group and 8.20 +/
      1.13/MUL in the control group (p = 0.005). The blood platelet count, CRP level,
      and ESR were significantly higher in the active PTB group than in the control
      group (p < 0.0001). In the PTB group, CRP levels (r = 0.26, p = 0.003) and ESR (r
      = 0.39, p = 0.003), but not MPV (p = 0.80), were significantly correlated with
      the radiologic extent of the disease. CONCLUSIONS: The MPV was lower in patients
      with PTB than in healthy controls, however, the difference was limited. The MPV
      does not reflect the severity of the disease. The use of MPV as an inflammation
      marker and a negative acute-phase reactant in PTB does not seem to be reliable.

PMID- 24581085
TI  - Fungiform papillary glossitis.

PMID- 24581086
TI  - Transcriptional effects of gene dose reduction.
AB  - Large-scale gene dose reductions usually lead to abnormal phenotypes or death.
      However, male mammals, Drosophila, and Caenorhabditis elegans have only one X
      chromosome and thus can be considered as monosomic for a major chromosome.
      Despite the deleterious effects brought about by such gene dose reduction in the
      case of an autosome, X chromosome monosomy in males is natural and innocuous.
      This is because of the nearly full transcriptional compensation for X chromosome
      genes in males, as opposed to no or partial transcriptional compensation for
      autosomal one-dose genes arising due to deletions. Buffering, the passive
      absorption of disturbance due to enzyme kinetics, and feedback responses
      triggered by expression change contribute to partial compensation. Feed-forward
      mechanisms, which are active responses to genes being located on the X, rather
      than actual gene dose are important contributors to full X chromosome
      compensation. In the last decade, high-throughput techniques have provided us
      with the tools to effectively and quantitatively measure the small-fold
      transcriptional effects of dose reduction. This is leading to a better
      understanding of compensatory mechanisms. 

PMID- 24581087
TI  - Graphene nanopore support system for simultaneous high-resolution AFM imaging and
      conductance measurements.
AB  - Accurately defining the nanoporous structure and sensing the ionic flow across
      nanoscale pores in thin films and membranes has a wide range of applications,
      including characterization of biological ion channels and receptors, DNA
      sequencing, molecule separation by nanoparticle films, sensing by block co
      polymers films, and catalysis through metal-organic frameworks. Ionic conductance
      through nanopores is often regulated by their 3D structures, a relationship that
      can be accurately determined only by their simultaneous measurements. However,
      defining their structure-function relationships directly by any existing
      techniques is still not possible. Atomic force microscopy (AFM) can image the
      structures of these pores at high resolution in an aqueous environment, and
      electrophysiological techniques can measure ion flow through individual nanoscale
      pores. Combining these techniques is limited by the lack of nanoscale interfaces.
      We have designed a graphene-based single-nanopore support (~5 nm thick with ~20
      nm pore diameter) and have integrated AFM imaging and ionic conductance recording
      using our newly designed double-chamber recording system to study an overlaid
      thin film. The functionality of this integrated system is demonstrated by
      electrical recording (<10 pS conductance) of suspended lipid bilayers spanning a
      nanopore and simultaneous AFM imaging of the bilayer. 

PMID- 24581088
TI  - The 2013 American College of Cardiology (ACC)/American Heart Association (AHA)
      guidelines for cholesterol management and for cardiovascular risk stratification:
      a reappraisal.

PMID- 24581089
TI  - Incidence of cardiovascular diseases and associated risk factors among subjects
      with type 2 diabetes - an 11-year follow up study.
AB  - AIMS: This study was planned to assess the development of cardiovascular disease
      (CVD) events over an 11-year period and to identify the associated risk factors
      that could predict the onset of CVD among subjects with type 2 diabetes. METHODS:
      Retrospective data of 249 patients (M:F 149:100) with type 2 diabetes, from a
      cohort of 7800 patients, attending a tertiary care center for diabetes from
      January 2000 to December 2011 were retrieved and analyzed for this study.
      Sociodemographic and habitual risk factors, baseline diabetes duration, HbA1c and
      time of onset of CVD and its risk factors were collected from case records.
      Person-years method was used to calculate incident rate of CVD. Binary logistic
      regression analyses were done to identify predictors associated with CVD and its
      risk factors. RESULTS: Incidence of CVD among subjects with diabetes was 5.6
      cases/1000 person-years. Nearly 60% developed hypertension and dyslipidemia or
      both during the 11-year period. The most common complication was neuropathy
      (14.4%). Smoking [OR (95%CI)] [9.26 (1.6-54.9)] (p = 0.014) and heavy alcohol
      consumption [8.7 (1.1-69.8)] (p = 0.04) were significantly associated with CVD.
      Higher BMI was significantly associated with hypertension and dyslipidemia [2.4
      (1.3-4.3)] (p = 0.003). CONCLUSIONS: Smoking and heavy alcohol consumption were
      significantly associated with CVD, and increased BMI was significantly associated
      with hypertension and dyslipidemia among subjects with type 2 diabetes in this
      study population. These findings emphasize the need for early identification and
      modification of risk factors associated with CVD events in patients with
      diabetes.

PMID- 24581090
TI  - A prospective study evaluating efficacy of polymer free Pronova XR stent in
      treatment of denovo coronary artery stenosis.
AB  - BACKGROUND: Drug eluting stents have remarkably improved results of percutaneous
      coronary angioplasty. Most of the currently available drug eluting stents uses a
      durable polymer as drug carrier which has been implicated in local inflammatory
      response and continued incidence of late and very late stent thrombosis. The
      Pronova XR stent is one from those new generation polymer free sirolimus eluting
      stents in which pharmaceutical excipient is used for the timed release of
      sirolimus from the XR stent platform instead of a polymeric coating. METHODOLOGY:
      We consecutively recruited 121 patients undergoing elective or urgent PCI at our
      center. All the patients were followed up clinically and mandatory follow up
      angiogram at 6 months was done for one third of the total patients. An
      independent core lab analyzed paired angiograms. RESULTS: The primary efficacy
      endpoint was death, MI, TVR at 6 months which occurred in 6.66% patients. The QCA
      analysis showed reference vessel diameter of 2.5 + 0.44 mm at baseline and the
      minimal luminal diameter was 0.88 + 0.43 mm giving baseline diameter stenosis of
      65.26 + 15.89%. The immediate post procedure in-segment diameter stenosis
      assessed was 23.68 + 8.96% which increased to 36.02 + 24.48% at follow up with a
      late lumen loss of 0.25 + 0.76 mm at mean of 191 days. CONCLUSION: Coronary
      angioplasty with polymer free Pronova XR stents results in acceptable late lumen
      loss and very low target lesion revascularisation at short and intermediate term
      in unselected patients.

PMID- 24581091
TI  - CYP 450 2C19 polymorphisms in Indian patients with coronary artery disease.
AB  - BACKGROUND: Dual antiplatelet therapy is the cornerstone in the management of
      acute coronary syndromes (ACS) and prevention of stent thrombosis (ST). Genetic
      polymorphisms in CYP2C19 gene involved in hepatic activation of clopidogrel leads
      to clopidogrel non-responsiveness and may influence clinical outcomes. These
      polymorphisms in CYP2C19 gene and their impact on clinical outcome in coronary
      artery disease (CAD) have not been studied in Indian population. METHODS: We
      studied 110 consecutive patients (mean age 55.7 +/- 10.7 years; 90% male) taking
      clopidogrel with angiographically proven CAD for various genetic polymorphisms in
      CYP2C19 gene. Relationship between loss of function mutation and clinical
      presentation with recurrent ACS including ST was analyzed. RESULTS: Out of 110
      patients, 26 (23.64%) had normal genotype, 52 (47.23%) had loss of function
      mutation *2 and 39 (35.45%) had a gain of function mutation *17, 7 (6.36%)
      patients were undefined metabolizers (*2/*17) which were excluded from analyses.
      Final analyses included 103 patients, with 45 (40.90%) having loss of function.
      Overall 51 patients had ACS, with 27 developing recurrence while on clopidogrel.
      The prevalence of loss of function mutation was no different between the group
      with recurrences and those without recurrences (55.6% vs. 50%, p = 0.7). Two
      patients developed ST while on clopidogrel; both had loss of function mutation.
      CONCLUSION: CYP2C19 gene polymorphisms are common in Indian population. Loss of
      function mutation status did not affect the clinical outcomes. A larger study
      also considering P2Y12 receptor polymorphisms together with platelet activity
      testing, may be required to establish the role of CYP2C19 gene polymorphisms in
      clinical practice.

PMID- 24581092
TI  - Outcome of primary PCI - an Indian tertiary care center experience.
AB  - OBJECTIVE: To assess the feasibility and outcomes of primary percutaneous
      coronary intervention (PPCI) for ST-segment elevation myocardial infarction
      (STEMI) in Indian Scenario. METHODS: Between January 2005 and December 2012,
      consecutive STEMI patients who underwent PPCI within 12 h of onset of chest pain
      were prospectively enrolled in a PPCI registry. Patient demographics, risk
      factors, procedural characteristics, time variables and in-hospital and 30 day
      major adverse cardiovascular events (MACE) [death, reinfarction, bleeding, urgent
      coronary artery bypass surgery (CABG) and stroke] were assessed. RESULTS: A total
      of 672 patients underwent PPCI during this period. The mean age was 52 +/- 13.4
      years and 583 (86.7%) were males, 275 (40.9%) were hypertensives and 336 (50%)
      were diabetics. Thirty one (4.6%) patients had cardiogenic shock (CS). Anterior
      myocardial infarction was diagnosed in 398 (59.2%) patients. The median chest
      pain onset to hospital arrival time, door-to-balloon time and total ischemic
      times were 200 (10-720), 65 (20-300), and 275 (55-785) minutes respectively. In
      hospital adverse events occurred in 54 (8.0%) patients [death 28 (4.2%),
      reinfarction 8 (1.2%), major bleeding 9 (1.3%), urgent CABG 4 (0.6%) and stroke 1
      (0.14%)]. Nineteen patients with CS died (mortality rate - (61.3%)). At the end
      of 30 days, 64 (9.5%) patients had MACE [death 35 (5.2%), reinfarction 10 (2.1%),
      major bleeding 10 (1.5%), urgent CABG 4 (0.6%) and stroke 1 (0.1%)]. CONCLUSION:
      Our study has shown that PPCI is feasible with good outcomes in Indian scenario.
      Even though the recommended door-to-balloon time can be achieved, the total
      ischemic time remained long. CS in the setting of STEMI was associated with poor
      outcomes.

PMID- 24581093
TI  - Optical coherence tomography guided PCI - initial experience at Apollo Health
      City, Jubilee Hills, Hyderabad.
AB  - BACKGROUND: The capability of OCT to examine the structure of the arterial wall
      before or after PCI is superior to those of other imaging modalities. Therefore
      the application of OCT during PCI seems logical and has the potential to enhance
      our performance during the PCI procedures. METHODS: OCT was performed in fifty
      two patients out of which, 45 patients underwent PCI. Out of these 45 patients,
      in 25 patients both pre and post PCI OCT assessment was done. In 20 patients only
      post PCI OCT assessment was done. In seven patients PCI was not done due to
      nonsignificant obstruction, these seven patients were not included in final
      analysis. RESULTS: Over all OCT leads to management changes in 65% of the time it
      was used. Alteration of stent length was done in 56% of the cases when evaluated
      pre PCI. Alteration of stent diameter was done in 36% cases when evaluated pre
      PCI. Treatment of malapposition was done in 24% of total cases. Further balloon
      dilatation for vessel expansion was done in 15% of total cases. In one case left
      main stenting was done after proximal edge dissection. CONCLUSION: OCT makes
      better visualization of plaque, thrombus, stent malapposition, dissection, plaque
      prolapse and helps in optimization of PCI results. More extensive, long-term
      studies will be needed to assess the prognostic implications of these findings.

PMID- 24581094
TI  - Techniques and outcomes of transcatheter closure of complex atrial septal defects
      - single center experience.
AB  - OBJECTIVE: To prospectively study the techniques and outcomes of transcatheter
      closure of complex Atrial septal defects (ASD). STUDY DESIGN AND SETTINGS:
      Prospective single center study with experience in catheter closure of ASD. All
      patients with complex ASD suitable for device closure. OBJECTIVE: Analysis of
      outcomes of transcatheter closure of complex ASD in JIPMER Hospital over the past
      5-year period. METHODS: Complex ASD was predefined and patients satisfying
      inclusion and exclusion criteria are included. All the patients had meticulous
      Transesophageal echocardiography (TEE) imaging beforehand. Modifications of the
      conventional techniques were allowed on a case per case basis according to
      operator preference. Successfully intervened patients were followed up
      clinically. RESULTS: Out of the 75 patients enrolled, 69 patients had successful
      device closure (success rate 92%) despite challenging anatomy. Fifty-six (74%)
      patients had ASD >= 25 mm. Fifteen patients (20%) had defect size >= 35 mm and 20
      patients (26.6%) had devices implanted with >= 35 mm waist size. Fifty percent of
      patients had complete absence of aortic rim and 25% had deficient posterior rim.
      Twenty percent of patients had malaligned septum. Mean follow up period was 3.2
      years. CONCLUSIONS: Trans catheter closure is feasible in anatomically complex
      substrates of Secundum ASD. Careful case selection, scrupulous imaging protocol,
      and expertise in modified techniques are mandatory for successful outcomes.

PMID- 24581095
TI  - Hybrid intraoperative pulmonary artery stenting in redo congenital cardiac
      surgeries.
AB  - OBJECTIVE: Reconstruction of branch pulmonary arteries (PAs) can be challenging
      in redo congenital heart surgeries. Treatment options like percutaneous stent
      implantation and surgical patch angioplasty may yield suboptimal results. We
      present our experience with hybrid intraoperative stenting which may be an
      effective alternative option. METHODS: We retrospectively analyzed data of all
      patients with PA stenosis who underwent intraoperative PA branch stenting in our
      institution between January 2011 and December 2012. RESULTS: Ten patients [6
      females, median age 10 (1.4 to 37) years], underwent hybrid stenting of the PA.
      Primary cardiac diagnoses were pulmonary atresia with ventricular septal defect
      (VSD) in three patients, pulmonary atresia with intact ventricular septum in two,
      Tetralogy of Fallot (TOF) in one, Double outlet right ventricle (DORV) with
      pulmonary stenosis (PS) in one, complex single ventricle in two and VSD with
      bilateral branch PA stenosis in one patient. Concomitant surgeries were
      revision/reconstruction of RV-PA conduit in 4, Fontan completion in 4, repair of
      TOF with conduit placement in 1 and VSD closure in 1 patient. The left PA was
      stented in 7, the right in 2 and both in 1, with a total of 11 stents. There were
      no complications related to stent implantation. Two early postoperative deaths
      were unrelated to stent implantation. At mean follow-up period of 14.8 (12-26)
      months, stent position and patency were satisfactory in all survivors. None of
      them needed repeat dilatation or surgical reintervention. CONCLUSION: Hybrid
      stenting of branch PA is a safe and effective option for PA reconstruction in
      redo cardiac surgeries. With meticulous planning, it can be safely performed
      without fluoroscopy.

PMID- 24581096
TI  - Coronary artery disease in patients undergoing cardiac surgery for non-coronary
      lesions in a tertiary care centre.
AB  - BACKGROUND: The objective of the present study was to determine the prevalence of
      coronary artery disease (CAD) in patients undergoing surgery for various valvular
      as well as non-valvular cardiac pathologies. METHODS: Patients with various
      valvular and non-valvular pathologies were selected. All patients with age >= 40
      years and an indication for open heart surgery underwent pre-operative coronary
      angiogram and were included in the study. RESULTS: The mean age was 51.5 +/- 9.02
      years. 178 (59.3%) patients were males and 122 (40.7%) patients were females. Out
      of 300 patients, 270 (90%) patients had valvular heart disease (VHD) and 30 (10%)
      patients had non-valvular heart disease. Rheumatic heart disease (RHD), mitral
      valve prolapse (MVP), degenerative aortic valve disease (DAVD) and bicuspid
      aortic valve (BAV) was present in 161 (53.7%), 17 (5.7%), 60 (20%) and 32 (10.7%)
      patients respectively. Overall, 26 (8.7%) patients were found to have significant
      CAD. CAD was significantly more common in patients with VHD as compared to
      patients with other etiologies (1 patient, 3.3%, p < 0.05). In the valvular
      group, DAVD patients had maximum prevalence of CAD (14 patients, 23.4%, p <
      0.05). In the group with CAD, the presence of variables such as age >60 years,
      male sex, typical angina, HT, dyslipidemia and smoking were significantly greater
      as compared to those with normal coronaries. CONCLUSION: The overall prevalence
      of CAD among patients undergoing non-coronary cardiac surgery is 8.7%. Coronary
      artery disease is relatively uncommon in patients with rheumatic VHD (4.9%),
      while its prevalence is highest in DAVD (23.4%).

PMID- 24581097
TI  - Alcohol septal ablation for hypertrophic obstructive cardiomyopathy - 8 years
      follow up.
AB  - BACKGROUND: Alcohol septal ablation is emerging as an alternative to surgical
      myectomy in the management of symptomatic cases of Hypertrophic obstructive
      cardiomyopathy (HOCM). This involves injection of absolute alcohol into 1st
      septal perforator thereby producing myocardial necrosis with resultant septal
      remodelling within 3-6 months. This results in reduction of septal thickness and
      LV outflow gradients with improvement in symptoms. METHODS: Fifty three patients
      had undergone alcohol septal ablation, there were 2 early and 2 late deaths and 4
      patients lost to follow up. Forty-five (85%) of them were followed up to a mean
      period of 96 +/- 9.2 months. Clinical, ECG, and Echocardiographic parameters were
      evaluated during follow up. RESULTS: Only 4 out of 51 patients remained in NYHA
      class III or IV at the end of 6 months. Significant reduction of LV outflow
      gradients (79 +/- 35 to 34 +/- 23 mmHg) and septal thickness (23 +/- 4.7 mm to 19
      +/- 3 mm) were observed during 6 months follow up. Beyond 6 months there was no
      further decrease in either septal thickness or LVOT gradients noted. Ten percent
      of patients needed pacemaker implantation. There was 92% survival at the end of 8
      years. CONCLUSION: Alcohol septal ablation is a safe and effective nonsurgical
      procedure for the treatment of HOCM. By minimizing the amount of alcohol to <= 2
      ml, one can reduce complications and mortality. The long-term survival is
      gratifying.

PMID- 24581098
TI  - Preventing rheumatic fever: M-protein based vaccine.
AB  - Group A beta hemolytic streptococcus (GAS), the organism which initiates
      rheumatic fever (RF) continues to be sensitive to penicillin. However, penicillin
      cannot prevent RF if the preceding sore throat is asymptomatic in more than 70
      percent children. Prevention of rheumatic fever (RF) may be possible only with
      the use of a vaccine. Efforts to design a vaccine based on emm gene
      identification of GAS, M-protein going on for more than 40 years, is unlikely to
      succeed. M-protein is strain specific. Infection with one strain does not provide
      immunity from infection with another strain. Based on the emm gene
      identification, of 250 or more identified strains of GAS, the distribution is
      heterogenous and keeps changing. The M-protein gene sequence of the organism
      tends to mutate. A vaccine prepared from available strains may not be effective
      against a strain following mutation. Lethal toxic shock syndrome due to GAS
      infection has been described with organisms without identifiable or functional M
      protein. M-protein has been excluded as the antigen responsible for acute
      glomerulonephritis (GN). Therefore M-protein plays no role in one suppurative
      (toxic shock syndrome) and one non-suppurative (acute GN) manifestation due to
      GAS infection. Lastly there is no direct evidence to indicate that M-protein is
      involved in inducing RF. The role of M-protein and the GAS component resulting in
      the suppurative manifestations of GAS infections like pyoderma, septic arthritis
      or necrotizing fasciitis etc is unknown. For a vaccine to be effective, an
      epitope of the streptococcus which is stable and uniformly present in all
      strains, needs to be identified and tested for its safety and efficacy. The
      vaccine if and when available is expected to prevent GAS infection. Preventing
      GAS infection will prevent all the suppurative as well as non-suppurative
      manifestations including RF.

PMID- 24581099
TI  - Wearable cardioverter defibrillator: a life vest till the life boat (ICD)
      arrives.
AB  - It is well established that implantable cardioverter defibrillator (ICD) is a
      life saving device ensuring protection against life threatening ventricular
      arrhythmias. But there are certain situations like a recent myocardial infarction
      where the standard guidelines do not recommend the implantation of an ICD while
      the patient can still be at a risk of demise due to a life threatening
      ventricular arrhythmia. There could also be a temporary indication for protection
      while explanting an infected ICD system. The wearable cardioverter defibrillator
      (WCD) is a device which comes to the rescue in such situations. In this brief
      review, we discuss the historical aspects of the development of a WCD, technical
      aspects as well as the clinical trial data and real world scenario of its use. 

PMID- 24581100
TI  - The Indian Consensus Document on cardiac biomarker.
AB  - Despite recent advances, the diagnosis and management of heart failure evades the
      clinicians. The etiology of congestive heart failure (CHF) in the Indian scenario
      comprises of coronary artery disease, diabetes mellitus and hypertension. With
      better insights into the pathophysiology of CHF, biomarkers have evolved rapidly
      and received diagnostic and prognostic value. In CHF biomarkers prove as measures
      of the extent of pathophysiological derangement; examples include biomarkers of
      myocyte necrosis, myocardial remodeling, neurohormonal activation, etc. In CHF
      biomarkers act as indicators for the presence, degree of severity and prognosis
      of the disease, they may be employed in combination with the present conventional
      clinical assessments. These make the biomarkers feasible options against the
      present expensive measurements and may provide clinical benefits. 

PMID- 24581101
TI  - A cost effective endovascular approach for management of post-catheterization
      profunda femoris artery pseudoaneurysm using thrombin.
AB  - Post-catheterization PSA is one of the most commonly encountered vascular
      complications of cardiac and peripheral angiographic procedures. We report the
      case of patient who developed deep-seated profunda femoris artery pseudoaneurysm
      (PSA) following cardiac catheterization. Despite, repeated ultrasound guided
      compressions the PSA failed to close and instead produced local site pressure
      ulcers. The secondary infection followed which precluded use of percutaneous
      thrombin injection. The PSA was finally closed via a total endovascular technique
      combining intravascular thrombin injection and coil embolization, thus obviating
      the need for expensive measures like cover stents or invasive surgical repairs. 

PMID- 24581102
TI  - Adenosine induced coronary spasm - a rare presentation.
AB  - Adenosine is commonly used as a pharmacological agent in myocardial perfusion
      imaging, as an antiarrhythmic agent, and in Cath Lab. during PCI for treating no
      reflow phenomenon. Coronary spasm has been reported following adenosine injection
      during stress imaging. We report a rare complication with ST segment elevation,
      following adenosine injection, given for treatment of supraventricular
      tachycardia. 

PMID- 24581103
TI  - Paravalvular leak closure with two large size devices.
AB  - Paravalvular leaks (PVL) after valve replacement surgeries are not uncommon. A
      significant number of these patients need some form of intervention as they
      commonly present with heart failure or severe hemolysis. Surgical correction is
      associated with high mortality and morbidity. Device closure of PVLs has been
      found to have good results. Since there are no devices designed specifically for
      PVL closure, large PVL closure is difficult. Occasional larger PVLs have been
      closed with a combination of a device and smaller coils. We present here a case
      of very large sized mitral PVL, in a patient with high risk for surgery, which
      was closed with two large size devices.

PMID- 24581104
TI  - Congenital anomalous/aberrant systemic artery to pulmonary venous fistula:
      closure with vascular plugs & coil embolization.
AB  - A 7-month-old girl with failure to thrive, who, on clinical and diagnostic
      evaluation [echocardiography & CT angiography] to rule out congenital heart
      disease, revealed a rare vascular anomaly called systemic artery to pulmonary
      venous fistula. In our case, there was dual abnormal supply to the entire left
      lung as(1) anomalous supply by normal systemic artery [internal mammary
      artery](2) and an aberrant feeder vessel from the abdominal aorta. Left Lung had
      normal bronchial connections and normal pulmonary vasculature. The fistula
      drained through the pulmonary veins to the left atrium leading to 'left-left
      shunt'. Percutaneous intervention in two stages was performed using Amplatzer
      vascular plugs and coil embolization to close them successfully. The patient
      gained significant weight in follow up with other normal developmental and mental
      milestones. 

PMID- 24581105
TI  - Brugada syndrome with a novel missense mutation in SCN5A gene: a case report from
      Bangladesh.
AB  - Brugada syndrome is an inherited cardiac arrhythmia that follows autosomal
      dominant transmission and can cause sudden death. We report a case of Brugada
      syndrome in a 55-year-old male patient presented with recurrent palpitation,
      atypical chest pain and presyncope. ECG changes were consistent with type 1
      Brugada. Gene analysis revealed a novel missense mutation in SCN5A gene with a
      genetic variation of D785N and a nucleotide change at 2353G-A. One of his
      children also had the same mutation. To our knowledge this is the first
      genetically proved case of Brugada syndrome in Bangladesh. 

PMID- 24581106
TI  - Ventricular tachycardia from intracardiac hematoma in the setting of blunt
      thoracic trauma.
AB  - In the victims of motor vehicle accidents, unrecognized myocardial injuries may
      pose diagnostic and therapeutic challenges. Herein, we present a case of a 17
      year-old man who developed multiple ventricular premature complexes and
      nonsustained ventricular tachycardia in the setting of blunt chest trauma from a
      motor vehicle accident. We discuss significance of the electrocardiographic
      abnormalities in making an accurate diagnosis of cardiac hematoma and its
      management.

PMID- 24581107
TI  - Use of external defibrillator jacket to facilitate safe delivery of radiotherapy
      for lung cancer - a report of two cases.
AB  - The increasing rate of implantable cardioverter defibrillator (ICD) implantation
      coupled with shared risk factors between lung cancer and ischemic cardiac disease
      means that the need for radiotherapy in cardiac device patients is set to become
      commonplace. We describe two cases referred to our electrophysiology service over
      a 6-month period. Both had been diagnosed with lung cancer in tissue directly
      posterior to a previously implanted ICD device. The cases highlight the risks to
      device function caused by ionizing radiation, the practical difficulties and
      ethical dilemmas of delivering radiotherapy to cardiac device patients safely and
      a novel setting for the use of a wearable defibrillator system. 

PMID- 24581108
TI  - Refractory atrial fibrillation effectively treated with ranolazine.
AB  - Atrial fibrillation is the most common sustained cardiac arrhythmia which is
      often troublesome to manage. Currently, rhythm and rate control medications are
      the mainstays of therapy. In 2 amiodarone-refractory highly symptomatic patients,
      an innovative approach using ranolazine, which selectively acts on Na+ channels
      and delays atrial depolarization, was tried successfully. 

PMID- 24581109
TI  - Cystic lymphangioma of pericardium presenting as isolated chylopericardium - a
      case report.
AB  - Isolated chylopericardium due to cystic lymphangioma of pericardium is a rare
      entity. We report a case of asymptomatic chylopericardium in a young male who
      presented with cardiomegaly. Echocardiography revealed massive pericardial
      effusion without tamponade. Pericardiocentesis yielded 1.25 L of tea-colored
      fluid which showed triglyceride level of 1723 mg/dL and cholesterol of 1021 mg/dL
      with a cholesterol to triglyceride ratio of <1, characteristic of chylous fluid.
      Lymphoscintigraphy using 99Tc demonstrated lymphatic leak around the heart
      region. Fusion of MRI images with lymphoscintigraphy was taken with a view of
      localizing the leak site; it demonstrated enhancement in the pericardial space.
      Surgery was done via right lateral thoracotomy. Thoracic duct was ligated above
      diaphragm and pericardial window created by anterior pericardiectomy. The patient
      had an uneventful recovery and was well after 6 months of follow up. Pericardial
      biopsy showed cystic lymphangioma of pericardium.

PMID- 24581110
TI  - A unique and unexplained ricochet leak post PCI - successfully treated with intra
      coronary glue.
AB  - We herein describe a unique case of coronary artery perforation treated with
      covered stent with repeat cardiac tamponade resulting out of a fresh unexplained
      leak from a remote vessel (Ricochet) and successfully treated with intra-coronary
      injection of sterile synthetic glue, cyanoacrylate. 

PMID- 24581111
TI  - Stress echo for evaluation of valvular heart disease.
AB  - Resting echocardiography is the most important tool for diagnosing valvular heart
      disease. However, treatment planning in valvular heart diseases may require
      additional information in some patients, particularly asymptomatic patients with
      severe valve disease or symptomatic patients with moderate disease. Stress
      echocardiography provides invaluable information in these situations and aids
      decision making. Stress echocardiography is performed using either physical
      stress or dobutamine stress and various valve parameters are monitored during the
      stress. Further, the ventricular performance, which is an important determinant
      of outcome in valve disease is also closely monitored during stress which helps
      immensely in planning the intervention. Lastly, possibility of associated
      coronary artery disease can also be evaluated, especially in the elderly. This
      article discusses the role of stress evaluation in assessment of valve disease in
      the commonly encountered clinical situations. 

PMID- 24581112
TI  - A case of 'Masquerading' bundle branch block: a forgotten concept.
AB  - 'Masquerading' bundle branch block (right bundle branch block in the precordial
      leads with left bundle branch block in frontal leads and left axis deviation) is
      seen most commonly with coronary artery disease and hypertension. No definite
      explanation is available so far for these changes. We are presenting a case of
      rare congenital intranuclear inclusion myopathy with congestive heart failure and
      'Masquerading' bundle branch block in ECG. 

PMID- 24581113
TI  - Giant pulmonary artery aneurysm in a 6-year-old child.
AB  - A 6-year-old female child was admitted with complaints of progressive dyspnea on
      exertion since last 3 years. She was saturating 100% on room air with stable
      vitals. On clinical examination, left precordial bulge was seen with prominent
      epigastric pulsations. Chest X-ray showed rightward shift of mediastinum and huge
      homogenous opacity occupying almost entire left lung field. On two-dimensional
      echocardiography, a large aneurysmal mass was seen occupying left hemithorax
      which was suspected to be arising from pulmonary artery but its exact site of
      origin could not be determined. A small patent ductus arteriosus (PDA) was also
      seen. PDA could be seen directly supplying the aneurysm (Fig. 1). CT angiography
      was done to confirm the diagnosis. It showed a huge aneurysmal sac measuring 12
      cm * 8.9 cm * 14 cm, arising from left pulmonary artery (LPA) opposite to the
      site of insertion of PDA. Sac was occupying most of the left lung and pushing
      down the left diaphragm (Fig. 2). Cause of formation of such a huge aneurysm
      could not be found out. Surgery was performed and mouth of the sac was closed
      along with ligation of duct, repair of LPA and drainage of the sac. After
      surgery, lung expansion was good. Patient was discharged and she is doing well.

PMID- 24581114
TI  - Evaluation of ischemic heart disease and viability by cardiac MRI.
AB  - In ischemic heart disease, cardiac MRI, besides being the gold standard for
      evaluation of quantitative ventricular function, enables evaluation of myocardial
      wall thickness, T2-weighted imaging for myocardial edema and infarct
      quantification and transmurality. Delayed hyperenhancement sequences are highly
      predictive of scar formation, being associated with myocyte necrosis. The extent
      and transmurality of delayed hyperenhancement has prognostic implications and is
      inversely proportional to the degree of functional recovery after acute
      myocardial infarction. A greater transmural extent of infarction (eg,
      hyperenhancement involving >50% of the wall thickness) can predict regions that
      are less likely to improve in function after therapy. The ultimate focus of MRI
      in ischemic heart disease is in diagnosis, quantification of myocardium at risk,
      salvageable myocardium, perfusion defects and differentiation of viable
      myocardium from non viable myocardium to enable prognostication.

PMID- 24581116
TI  - Optimized conditions for successful transfection of human endothelial cells with
      in vitro synthesized and modified mRNA for induction of protein expression.
AB  - BACKGROUND: The induction of protein synthesis by exogenous delivery of coding
      synthetic mRNA in desired cells is an auspicious strategy in the fields of basic
      cell biology, regenerative medicine, treatment of diseases, and reprogramming of
      cells. Here, we produced modified messenger RNA (mRNA) with reduced immune
      activation potential and increased stability and performed transfection
      experiments with different cells, HEK293 cells, BJ fibroblasts, and endothelial
      cells (ECs). RESULTS: The mRNA induced protein expression in cells was analyzed
      after transfection with different mRNA amounts and transfection reagents using
      flow cytometry. Different cell types showed different degrees of eGFP expression.
      HEK293 cells exhibited the highest eGFP expression compared to the BJ fibroblasts
      and ECs. However, the mRNA induced eGFP expression was detected in all cell types
      until 3 days after transfection. Already, the use of 0.5 MUg of the synthesized
      mRNA led to the significant expression of eGFP in ECs. From all analyzed ECs
      approximately 87% were eGFP positive, which showed a high transfection
      efficiency. CONCLUSIONS: The synthesis of stabilized mRNA and the high
      transfection efficiency will enable the mRNA engineering of ECs as well as other
      somatic cells. The delivery of synthetic exogenous mRNA into cells allows the
      transient expression of desired proteins, which would be normally not expressed
      by the cells.

PMID- 24581115
TI  - Spectrum of heart disease in children under 5 years of age at Liaquat University
      Hospital, Hyderabad, Pakistan.
AB  - OBJECTIVE & METHODOLOGY: This was a descriptive cross sectional study of one year
      duration conducted in Pediatric department of Liaquat University Hospital,
      Hyderabad. The objective was to assess the clinical pattern, age distribution and
      type of heart diseases in children under 5 years of age. In this study 150
      children with suspicion of cardiac problem were enrolled. RESULT: Among 150
      cardiac patients 55.3% were male and 44.7% were female. Congenital heart diseases
      (CHD) seen in 89.3% and 10.7% had acquired heart disease. Among CHD 74.6% were
      Acyanotic lesions while cyanotic lesions were seen in 23.9% and 1.5% were cases
      of dextrocardia. Ventricular septal defect was the commonest Acyanotic lesion
      (29.9%) followed by atrial septal defect (25.4%). Among cyanotic heart diseases
      tetralogy of Fallot was the commonest lesion seen in 11.2% followed by
      transposition of great arteries and complex heart defect 5.2% and 3%
      respectively. Among acquired heart disease myocarditis was the commonest disease
      accounts 94% and pericardial effusion was seen in 6%. CONCLUSION: Regarding the
      type of congenital heart defect acyanotic defect was more common than cyanotic
      with ventricular septal defect commonest lesion. Tetralogy of Fallot's was
      commonest in cyanotic group. Availability of expertise locally will lead to more
      patients getting surgical treatment at an earlier age thereby reducing morbidity
      and mortality and improving quality of life for these children.

PMID- 24581118
TI  - The spatial and temporal distributions of arthropods in forest canopies: uniting
      disparate patterns with hypotheses for specialisation.
AB  - Arguably the majority of species on Earth utilise tropical rainforest canopies,
      and much progress has been made in describing arboreal assemblages, especially
      for arthropods. The most commonly described patterns for tropical rainforest
      insect communities are host specificity, spatial specialisation (predominantly
      vertical stratification), and temporal changes in abundance (seasonality and
      circadian rhythms). Here I review the recurrent results with respect to each of
      these patterns and discuss the evolutionary selective forces that have generated
      them in an attempt to unite these patterns in a holistic evolutionary framework.
      I propose that species can be quantified along a generalist-specialist scale not
      only with respect to host specificity, but also other spatial and temporal
      distribution patterns, where specialisation is a function of the extent of
      activity across space and time for particular species. When all of these
      distribution patterns are viewed through the paradigm of specialisation,
      hypotheses that have been proposed to explain the evolution of host specificity
      can also be applied to explain the generation and maintenance of other spatial
      and temporal distribution patterns. The main driver for most spatial and temporal
      distribution patterns is resource availability. Generally, the distribution of
      insects follows that of the resources they exploit, which are spatially
      stratified and vary temporally in availability. Physiological adaptations are
      primarily important for host specificity, where nutritional and chemical
      variation among host plants in particular, but also certain prey species and
      fungi, influence host range. Physiological tolerances of abiotic conditions are
      also important for explaining the spatial and temporal distributions of some
      insect species, especially in drier forest environments where desiccation is an
      ever-present threat. However, it is likely that for most species in moist
      tropical rainforests, abiotic conditions are valuable indicators of resource
      availability, rather than physiologically limiting factors. Overall, each
      distribution pattern is influenced by the same evolutionary forces, but at
      differing intensities. Consequently, each pattern is linked and not mutually
      exclusive of the other distribution patterns. Most studies have examined each of
      these patterns in isolation. Future work should focus on examining the
      evolutionary drivers of these patterns in concert. Only then can the relative
      strength of resource availability and distribution, host defensive phenotypes,
      and biotic and abiotic interactions on insect distribution patterns be
      determined. 

PMID- 24581117
TI  - A genomic perspective on a new bacterial genus and species from the
      Alcaligenaceae family, Basilea psittacipulmonis.
AB  - BACKGROUND: A novel Gram-negative, non-haemolytic, non-motile, rod-shaped
      bacterium was discovered in the lungs of a dead parakeet (Melopsittacus
      undulatus) that was kept in captivity in a petshop in Basel, Switzerland. The
      organism is described with a chemotaxonomic profile and the nearly complete
      genome sequence obtained through the assembly of short sequence reads. RESULTS:
      Genome sequence analysis and characterization of respiratory quinones, fatty
      acids, polar lipids, and biochemical phenotype is presented here. Comparison of
      gene sequences revealed that the most similar species is Pelistega europaea, with
      BLAST identities of only 93% to the 16S rDNA gene, 76% identity to the rpoB gene,
      and a similar GC content (~43%) as the organism isolated from the parakeet, DSM
      24701 (40%). The closest full genome sequences are those of Bordetella spp. and
      Taylorella spp. High-throughput sequencing reads from the Illumina-Solexa
      platform were assembled with the Edena de novo assembler to form 195 contigs
      comprising the ~2 Mb genome. Genome annotation with RAST, construction of
      phylogenetic trees with the 16S rDNA (rrs) gene sequence and the rpoB gene, and
      phylogenetic placement using other highly conserved marker genes with ML Tree all
      suggest that the bacterial species belongs to the Alcaligenaceae family. Analysis
      of samples from cages with healthy parakeets suggested that the newly discovered
      bacterial species is not widespread in parakeet living quarters. CONCLUSIONS:
      Classification of this organism in the current taxonomy system requires the
      formation of a new genus and species. We designate the new genus Basilea and the
      new species psittacipulmonis. The type strain of Basilea psittacipulmonis is DSM
      24701 (= CIP 110308 T, 16S rDNA gene sequence Genbank accession number JX412111
      and GI 406042063).

PMID- 24581120
TI  - [Identification of proteins interacted with Bat3 using tandem affinity
      purification].
AB  - OBJECTIVE: To identify the specific protein interactions involved in Bat3
      mediated apoptosis. METHODS: Tandem affinity purification (TAP) was utilized to
      investigate Bat3-protein interactions, during which full-length human Bat3 fused
      with Strep2 and FLAG tag as a bait was used to screen the specific protein
      protein interactions. The isolated proteins were identified with mass
      spectrometry. RESULTS: TAP studies showed that Ubl4A was identified as a Bat3
      binding partner. Further investigation using co-immunoprecipitation confirmed
      that Bat3 was associated with Ubl4A. CONCLUSION: TAP was successfully established
      and is suitable for isolating the binding partners of Bat3.

PMID- 24581119
TI  - Revealing spatio-spectral electroencephalographic dynamics of musical mode and
      tempo perception by independent component analysis.
AB  - BACKGROUND: Music conveys emotion by manipulating musical structures,
      particularly musical mode- and tempo-impact. The neural correlates of musical
      mode and tempo perception revealed by electroencephalography (EEG) have not been
      adequately addressed in the literature. METHOD: This study used independent
      component analysis (ICA) to systematically assess spatio-spectral EEG dynamics
      associated with the changes of musical mode and tempo. RESULTS: Empirical results
      showed that music with major mode augmented delta-band activity over the right
      sensorimotor cortex, suppressed theta activity over the superior parietal cortex,
      and moderately suppressed beta activity over the medial frontal cortex, compared
      to minor-mode music, whereas fast-tempo music engaged significant alpha
      suppression over the right sensorimotor cortex. CONCLUSION: The resultant EEG
      brain sources were comparable with previous studies obtained by other
      neuroimaging modalities, such as functional magnetic resonance imaging (fMRI) and
      positron emission tomography (PET). In conjunction with advanced dry and mobile
      EEG technology, the EEG results might facilitate the translation from laboratory
      oriented research to real-life applications for music therapy, training and
      entertainment in naturalistic environments.

PMID- 24581121
TI  - [Relationship between female dyslipidemia and polymorphism of suppressor of
      cytokine signaling-3 in Xinjiang Uygur population].
AB  - OBJECTIVE: To explore whether the polymorphism of suppressor of cytokine
      signaling-3 (SOCS-3) and dyslipidemia are correlated in Uygur females. METHODS: A
      total of 1379 Uygur females from Xinjiang Uygur Autonomous Region were enrolled
      in this study. Three single nucleotide polymorphisms (SNPs), namely rs12953258,
      rs4969168, and rs9914220, were analyzed after being genotyped. RESULTS: Of these
      three SNPs, the frequency distribution of rs12953258 sites was found to be
      significantly different between dyslipidemia group and normal group (P=0.032).
      The frequency distribution of rs12953258 sites between the high-density
      lipoprotein-cholesterol (HDL-C) abnormal group and normal group also showed
      significant difference (P=0.029). Logistic regression analysis showed that the
      genotype AA of rs12953258 was a risk factor for dyslipidemia among the Uygur
      females [CC vs. AA:OR=3.271,95%CI(1.092-9.797), P=0.034]. The genotype AA of
      rs12953258 might be related to the decreased high HDL-C and increased
      trigleceride, whereas the genotype AA coupled with abnormal body mass index (BMI)
      were more likely to be linked with the higher prevalence of dyslipidemia in Uygur
      females. CONCLUSIONS: The polymorphism of SOCS-3 is correlated to the
      dyslipidemia in Uygur females in Xinjiang. Carriers of Genotype AA of rs12953258
      coupled with abnormal BMI are more susceptible to dyslipidemia.

PMID- 24581122
TI  - [Effects of stanniocalcin-1 and hypoxia-inducible factor-1alpha on mitochondrial
      membrane potential stability in renal carcinoma cells].
AB  - OBJECTIVE: To explore the effects of stanniocalcin-1 (STC-1) and hypoxia
      inducible factor-1alpha (HIF-1alpha) on the calcium and thus on the mitochondrial
      membrane potential (Deltapsim) in renal carcinoma cells. METHODS: We successfully
      established the renal carcinoma cell models with high HIF-1alpha gene expression.
      After various concentrations of STC-1 solutions were added to the culture medium,
      the proliferation of cells, expressions of HIF-1alpha and STC-1, levels of
      Ca(2+), Deltapsim, and mPTP were detected by MTT, RT-PCR, ELISA, fluorescence
      spectrophotometry, and ultraviolet spectrophotometry, respectively. RESULTS: The
      proliferation of renal carcinoma cells and Deltapsim were improved after HIF
      1alpha gene transfection, STC-1 protein intervention, and STC-1 protein
      intervention after gene transfection. While the intracellular Ca(2+) level and
      mPTP were decreased significantly (P<0.05), all the changes were intensified with
      the gradual increase of STC-1. However, the increasing trend of cell
      proliferation gradually declined. CONCLUSION: HIF-1alpha may participate in
      malignant proliferation of renal carcinoma cells by promoting STC-1 proliferation
      or down-regulating Ca(2+); however, such an effect may be gradually attenuated
      due to the inhibitory effect of STC-1 on HIF-1alpha.

PMID- 24581123
TI  - [Effects of membrane protein ANO1 stable overexpression on laryngocarcinoma Hep-2
      cells].
AB  - OBJECTIVE: To explore the effects of ANO1 overexpression on the proliferation,
      detachment, spreading, and migration of laryngocarcinoma Hep-2 cell line.
      METHODS: ANO1-overexpressing Hep-2 cell line was selected as the assay group, and
      Hep-2 cell line with empty plasmid was selected as the control group. MTT assay
      was used to detect the proliferation abilities of Hep-2 cells in both two groups.
      Cell detachment assay and spreading assay were used to detect the detachment and
      spreading abilities of Hep-2 cells. Boyden chamber invasion assay, wound healing
      assay in vitro, and niflumic acid block chloride channel were used to detect the
      migration abilities of Hep-2 cells. All data were analyzed by SPSS 10.0 software
      package. RESULTS: Cell proliferation assay by MTT showed that, compared with the
      control group, the optical density value of assay group was not significantly
      different (P=0.62). The results of cell detachment assay and cell spreading assay
      showed the cell detachment rates and cell spreading rates in assay group were
      significantly higher than those in control group (P<0.0001). The results of
      Boyden chamber invasion assay showed the percentages of cells migrating through
      the membrane in assay group were significantly higher than those in control group
      (P<0.0001). The results of in vitro wound healing experiments showed the wound
      area rate in assay group was significantly lower than that in control group
      (P<0.0001). The results of niflumic acid blocking chloride channel experiments
      showed the wound area rates in assay group were significantly higher than those
      in control group (P<0.0001). CONCLUSION: ANO1 overexpression does not remarkably
      alter the proliferation rate of cancer cells, but increases the migration,
      spreading, and detachment capacities of head and neck squamous cell carcinoma.

PMID- 24581124
TI  - [Role of bone marrow mesenchymal stem cells in restoring the functions of
      degenerative nucleus pulposus cells].
AB  - OBJECTIVE: To explore the effects of bone mesenchymal stem cells (BMSCs) in
      restoring the functions of degenerative nucleus pulposus cells (dNPCs). METHODS:
      The animal models of degenerative nucleus pulposus were established by means of
      acupuncture and aspiration. The BMSCs as well as the normal and degeneratived
      nucleus pulposus cells of SD rats were isolated and cultured. The BMSCs/alginate
      gel complex and dNPCs/alginate gel complex were used for indirect co-culture in
      vitro, which was set as experiment group. The NPCs and dNPCs cultured alone as
      positive and negative controls. The cell growth conditions were observed by light
      microscopy, and suitable cells were selected to combine alginate gel stents and
      cultured in transwell plate. Seven days later, nucleus pulposus cells of each
      group were recycled, and the mRNA expressions of Collagen2, SOX 9, and Aggrecan
      were detected by RT-PCR, and the Collagen1, 2, and Aggrecan were detected by
      Western blotting and immunofluorescence. RESULTS: After non-contact co-culture
      for 7 days, the mRNA levels of Collagen2, SOX 9, and Aggrecan increased
      apparently in BMSCs+dNPCs group, while it was significantly lower in dNPCs sample
      (all P<0.05). The content of Collagen2 and Aggrecan detected by Western blotting
      in BMSCs+dNPCs group got close to NPCs sample, but it was significantly higher
      than dNPCs samples (all P<0.05), while the content of Collagen1in BMSCs+dNPCs
      group got close to NPCs samples, but it was significantly lower than dNPCs sample
      (P<0.05). Immunofluorescence results showed that cytoplasm was dyed red and the
      color near the caryon became dark in BMSCs+dNPCs group and dNPCs group;however,
      the colored scope of cytoplasm and the dark colored scope surrounding the caryon
      in BMSCs+dNPCs group was obviously larger than dNPCs group. CONCLUSION: Under a
      3D non-contact co-culture system, BMSCs can promote the expression of epimatrix
      of the dNPCs, which shows that BMSCs can restore the functions of dNPCs of
      intervertebral disc to certain extent.

PMID- 24581125
TI  - [Efficacy and safety of combination of sorafenib and transarterial
      chemoembolization in treating primary hepatocellular carcinoma].
AB  - OBJECTIVE: To evaluate the efficacy and safety of the combination of sorafenib
      and transarterial chemoembolization (TACE)in the treatment of primary
      hepatocellular carcinoma (HCC). METHODS: The clinical data of 10 patients with
      unresectable HCC treated by sorafenib combined with TACE in the Department of
      Radiology, the First Hospital of China Medical University were retrospectively
      analyzed. The efficacy was evaluated according to the modified Response
      Evaluation Criteria in Solid Tumors assessment. Survival was analyzed by Kaplan
      Meier method. Safety was evaluated according to the National Cancer Institute
      Common Toxicity Criteria for Adverse Events version 3.0. RESULTS: Among the 10
      patients, 2 achieved complete response, 3 achieved partial response, 3 achieved
      stable disease, and 2 experienced progressive disease. The median overall
      survival of the cohort was 29.5 months. Different degree of adverse drug
      reactions (ADRs) occurred in 9 patients but all were at grade 3 or lower. The
      most common ADRs were hand-foot skin reaction (7/10) and diarrhea (6/10).
      CONCLUSION: The combination of sorafenib and TACE is an effective and safe
      treatment for HCC.

PMID- 24581126
TI  - [Role of serum procalcitonin assay for diagnosis of spontaneous bacterial
      peritonitis in end-stage liver diseases].
AB  - OBJECTIVE: To explore the clinical value of serum procalcitonin (PCT) for
      predicting spontaneous bacterial peritonitis (SBP) in end-stage liver diseases.
      METHODS: The clinical data of 362 ascitic inpatients with end-stage liver
      diseases who had underwent serum PCT assay in our department from March 2011 to
      June 2013 were analyzed retrospectively. These patients were then divided into
      SBP group (n=178) and non-SBP group (n=184). The dynamic changes of the PCT
      values upon admission and after antibiotic treatment were compared. The receiver
      operating characteristic curve was drawn to identify the optimal cut-off value of
      serum PCT in diagnosing SBP. RESULTS: The positive rate of bacteria culture in
      ascites was only 4.6% (4/87) in SBP group. The median value of serum PCT was 0.73
      and 0.15 ng/ml in SBP group and non-SBP group (Z=-11.9, U=0.000), respectively,
      before antibiotic treatment. In the SBP group, the median value of serum PCT was
      1.73 ng/ml in 13 patients with positive culture findings, which was higher than
      the overall median value in SBP group. Among patients who were responsive to the
      antibiotic therapy, the median values of serum PCT were 0.40(n=46), 0.32(n=19),
      and 0.33 ng/ml(n=25), respectively, 3, 5, and 7 days after the effective
      antibiotics treatment, which were significantly lower than the pre-treatment
      levels [0.86(Z=-5.91, U=0.000), 0.72(Z=-3.10, U=0.002), and 0.79 ng/ml(Z=-4.37,
      U=0.000), respectively]. ROC analysis showed that a serum PCT value of more than
      0.462 ng/ml had a sensitivity of 83.7% and a specificity of 94.9%(AUC:0.95,
      95%CI:0.93-0.97, P=0.00) in diagnosing SBP in patients with end-stage liver
      diseases. CONCLUSIONS: Ascitic fluid positive rate is low in SBP patients. Serum
      PCT is a sensitive and specific marker for predicting peritoneal bacteria
      infection in end-stage liver disease patients with ascites. Higher serum PCT can
      be expected in these patients with heavier infections, it can also be used to
      evaluate the effectiveness of anti-bacteria therapies.

PMID- 24581127
TI  - [Correlations between cellular immunity and invasiveness in differentiated
      thyroid cancer].
AB  - OBJECTIVE: To investigate the relationship between the immunity and invasiveness
      in differentiated thyroid cancer (DTC). METHODS: Totally 74 DTC who were treated
      in Peking Union Medical College Hospital from September 2012 to December 2012
      were enrolled in this study. These 74 patients were divided into membrane
      invasion group (n=36) and without membrane invasion group (n=38); also, they were
      divided into distant metastasis group (n=18) and without distant metastasis group
      (n=56). Natural killer (NK) cells and T-cell subsets were chosen as indicators
      for cellular immunity to investigate the correlation between cellular immunity
      and invasiveness in DTC. RESULTS: Univariate analysis showed that the membrane
      invasion (Chi(2)=12.175, P=0.000) and distant metastasis (Chi(2)=8.139, P=0.006)
      correlated with cell immunity, whereas distant metastasis correlated with
      lymphocytic thyroiditis (Chi(2)=7.094, P=0.008). Further investigation shows that
      distant metastasis was associated with the percentage of CD8+T cell subgroup
      (Chi(2)=5.429, P=0.020), and membrane invasion was significantly associated with
      NK cells (Chi(2)=2.445, P=0.018) and CD4/CD8 disorder subgroup (Chi(2)=8.079,
      P=0.002). Multivariate analysis showed that cell immunity disorder was a risk
      factor for membrane invasion [OR=5.701,95%CI(2.075~15.666), P=0.001] and distant
      metastasis [OR=5.063,95%CI (1.571~16.320), P=0.008]. Further analysis showed that
      CD8+T cell was a risk factor for metastasis [OR=2.236,95%CI( 1.084~4.613),
      P=0.029], and CD4/CD8 disorders were the risk factors for membrane invasion
      [OR=2.802,95%CI(1.257~6.244), P=0.012]. CONCLUSION: Cell immunity in thyroid
      cancer has close relationship with membrane invasion and distant metastasis,
      especially when the percentage of CD8+T cells decreases and when the NK cells and
      CD4/CD8 are abnormal, which may lead to membrane invasion and distant metastasis.

PMID- 24581128
TI  - [Expression of metastasis-associated in colon cancer-1 in different stages of
      epithelial ovarian cancer].
AB  - OBJECTIVE: To investigate the expression of metastasis-associated in colon cancer
      1 (MACC1) in different International Federation of Gynecology and
      Obstetrics(FIGO)stages of epithelial ovarian cancer and its relationship with
      prognosis. METHODS: Between May 2008 and August 2010, 52 epithelial ovarian
      cancer patients were selected from the Department of Obstetrics and Gynecology of
      the First Affiliated Hospital of Zhengzhou University. Reverse transcription
      polymerase chain reaction (RT-PCR) and Western blotting were used to detect the
      expression of MACC1 mRNA and protein in the primary lesions of epithelial ovarian
      cancer patients, the levels of MACC1 in different stage patients were compared,
      and the relationship between expression of MACC1 and prognosis of ovarian cancer
      patients was analyzed by Kaplan-Meier analysis. RESULTS: The relative expression
      levels of MACC1 mRNA in epithelial ovarian cancer from 1 stage to 4 stage were
      0.72+/-0.01, 0.75+/-0.01, 0.78+/-0.01, and 0.81+/-0.02, respectively (F=51.305,
      P=0.000). The expression levels of MACC1 protein from 1 stage to 4 stage were
      0.71+/-0.04, 0.73+/-0.02, 0.76+/-0.01, and 0.84+/-0.05, respectively (F=65.142,
      P=0.000). At the end of the follow-up, the expression of MACC1 protein in
      recurrence and dead patients of 3-4 stages was obviously higher than that in the
      patients with stable disease (0.85+/-0.03 vs.0.74+/-0.05, F=72.324, P=0.000).
      Compared to 1-2 stage patients with lower MACC1 expression, the survival time of
      3-4 stage patients with higher MACCC1 expression was significantly shorter
      (chi(2)=29.804, P=0.000). CONCLUSIONS: Increased expression of MACC1 may indicate
      poor prognosis of ovarian cancer patients. Therefore, MACC1 may be a potential
      biomarker for advanced ovarian cancer.

PMID- 24581129
TI  - [Automated breast volume scanning in the diagnosis of breast intraductal
      papilloma].
AB  - OBJECTIVE: To investigate the value of automated breast volume scanning (ABVS) in
      the diagnosis of breast intraductal papilloma (IDP). METHODS: Totally 239 lesions
      in 213 women who were scheduled for open biopsy were investigated in this study.
      The patients underwent both ABVS and conventional ultrasound (US). According to
      the imaging diagnostic standards of IDP, the diagnostic accuracy for ABVS was
      calculated, and then compared with US, using histopathological examination as the
      gold standard. RESULTS: Among the 239 breast lesions studied, 85 were
      pathologically proved to be malignancies and 154 benign lesions, among which
      there were 26 cases of IDP. ABVS found 41 cases of IDP (17.2%), with the
      sensitivity, specificity, positive predictive value, negative predictive value,
      and accuracy being 88.5%, 91.5%, 56.1%, 98.5%, and 91.2%, respectively. In
      contrast, US found 32 cases of IDP (13.4%), with the sensitivity, specificity,
      positive predictive value, negative predictive value, and accuracy being 73.1%,
      93.9%, 59.4%, 96.6%, and 91.6%, respectively. CONCLUSION: ABVS coronal images can
      better display the structures of dilated lactiferous ducts and the intraluminal
      echoes, increase the diagnostic accuracy of IDP, and thus provide more
      information for the diagnosis and differential diagnosis of IDP.

PMID- 24581130
TI  - [Clinical and ultrasonic features of breast cancer in women older than 80 years].
AB  - OBJECTIVE: To summarize the clinical and ultrasonic features of breast cancer in
      women aged 80 and older. METHODS: A total of 60 patients (62 lesions) aged 80 and
      older with pathologically confirmed breast cancer from September 1993 to October
      2012 were enrolled in this study and their clinical manifestations, ultrasonic
      features, therapeutic methods, and prognoses were analyzed. RESULTS: Most
      patients (83.3%) went to see a doctor because of nodules touched by themselves.
      The average diameter of the carcinoma was (2.4+/-1.1)cm. Most tumors (75.8%) were
      invasive ductal carcinomas, followed by the mucinous carcinoma (11.3%). Among the
      45 lesions with ultrasound records, 40 (88.9%) were irregular in morphology; the
      aspect ratio of 35 lesions (77.8%) was less than 1;24 lesions (53.3%) had
      indistinct boundary;calcification existed in 21 lesions (46.7%); and 16 lesions
      (35.6%) had rear echo attenuation. The preoperative diagnostic accuracy of
      ultrasonography was 93.5%. In addition, 45 patients (75.0%) underwent breast
      tumor extended resection, 13 (21.7%) received modified radical mastectomy, 2
      patients (3.3%) underwent simple breast resection. No death was noted during the
      operation and there was no major peri-operative complications. Of 31 patients
      with complete follow-up records, 7 had recurrence or metastasis and 1 died of
      heart disease. CONCLUSIONS: Most breast cancers in women older than 80 years are
      relatively large, with typical ultrasonic features. The preoperative diagnosis is
      often accurate. Few lymphatic metastases exist, and the prognosis is good.
      Conservative surgeries are preferred for these elderly patients.

PMID- 24581131
TI  - [Clinical evaluation of 136 inpatients with bronchiectasis in Peking Union
      Medical College Hospital].
AB  - OBJECTIVE: To summarize the clinical features of bronchiectasis. METHODS: We
      retrospectively analyzed the clinical data of 136 patients who had been admitted
      to Peking Union Medical College Hospital from January 2010 to December 2012 due
      to bronchiectasis, which was confirmed by high-resolution computed tomography.
      RESULTS: The average age of these 136 patients (61 men and 75 women) was (57.7+/
      16.3) years. The average clinical history was (17.2+/-15.8) years. The exact
      etiology was unidentified in 77.2% (105/136) of the patients. The most commonly
      identified cause was previous infections (14.7%, 20/136), particularly
      tuberculosis. The main symptoms of bronchiectasis were cough and sputum
      production. The types of bronchiectasis were cylindrical in 37.7% (37/98),
      varicose in 40.8% (40/98), cystic in 21.4% (21/98) of these patients. Multilober
      involvement was most common (77.2%, 105/136). The most commonly involved lobes
      were left lower lobe (76.5%, 104/136). Of 77 patients who had undergone pulmonary
      function test, 47 (61.0%) showed obstructive. For each bronchiectasis type, the
      values (percentages of predicted) of forced expiratory volume in one second
      (FEV1) (P=0.918), forced vital capacity (FVC) (P=0.982), and FEV1/FVC (P=0.211)
      showed no statistical significance. The most commonly identified pathogen in
      sputum culture was Pseudomonas aeruginosa, which was sensitive to most broad
      spectrum antibiotics. Current infections were most common in patients with cystic
      bronchiectasis, among whom rales were frequently heard. CONCLUSIONS: Most
      bronchiectasis patients are old women. The main etiology is previous infection,
      especially tuberculosis. The main symptom of bronchiectasis is productive cough.
      Many patients can have obstructive pulmonary function. The distribution of
      lesions is diffuse, and the lesions are often seen in both lungs, particularly in
      the left lower lobe. Cystic bronchiectasis may be a more severe type, and should
      be carefully managed once identified by radiology.

PMID- 24581132
TI  - [Efficacy of entropy index in monitoring nociceptive stimulus in patients
      undergoing propofol-remifentanil general anesthesia].
AB  - OBJECTIVE: To evaluate the efficacy of reflex entropy (RE)/state entropy (SE) in
      monitoring the response to nociceptive stimulus during propofol-remifentanil
      infusion. METHODS: After the approval of the hospital ethics committee, sixty
      American Society of Anesthesiologists (ASA) classification 1-2 patients, aged 18
      65 years, receiving the hypogastrium operation undergoing general anesthesia,
      were randomly allocated to groups A and B with different remifentanil
      concentrations. After the concentration of propofol and remifentanil reached
      balance, tetanic stimulation, intubation, and incision were performed
      respectively with certain intervals. RE and SE were monitored during this
      procedure. RESULTS: Twelve patients were withdrawn from this study due to the use
      of vasoactive drugs. Finally, there were 28 cases in group A and 20 cases in
      group B. The RE and SE were not significantly changed before and after the
      tetanic stimulation in both groups (all P>0.05). Both RE and SE were
      significantly increased after intubation in group B (both P<0.05) and after skin
      incision in both groups (all P<0.05). Under the same stimulation, RE and SE
      showed no significant difference among groups administered with different levels
      of remifentanil (P>0.05). CONCLUSION: Under the anesthesia with
      propofol+remifentanil, nociceptive response may cause the increase of RE and SE.
      Therefore, RE and SE may be useful parameters for monitoring the nociceptive
      response during general anaesthesia.

PMID- 24581133
TI  - [Value of diffusion-weighted imaging in diagnosis of lymph node metastasis in
      patients with cervical cancer].
AB  - OBJECTIVE: To investigate the value of diffusion-weighted imaging (DWI) in the
      differentiation of metastatic lymph nodes from non-metastatic lymph nodes in
      cervical cancer. METHODS: In 65 patients who underwent lymph node dissection for
      cervical cancer, conventional MRI and DWI examinations were performed before
      surgery. Of the 1590 total dissected pelvic lymph nodes, 392 enlarged nodes with
      a short-axis diameter (S )of 5 mm or greater were included for further analysis.
      Each of the size-based criteria [i.e., S, long-axis diameter (L), and S/L ratio]
      and apparent diffusion coefficient(ADC)-based criteria (i.e., ADCmin, ADCmean,
      rADCmin, rADCmean) were compared between metastatic lymph nodes and non
      metastatic lymph nodes. RESULTS: There were statistically significant differences
      between metastatic and non-metastatic lymph nodes in S, L, S/L ratio, ADCmin,
      ADCmean, rADCmin, and rADCmean (all P<0.0001). The Az of the ADCmin (0.956) was
      greater than that of the other ADC-based criteria and all size-based criteria.
      Using ADCmin=759.0*10(-6) mm(2)/s, the sensitivity and specificity for
      differentiating metastatic from non-metastatic lymph nodes were 95.2% and 92.1%,
      respectively. CONCLUSION: DWI, particularly ADCmin, is feasible for
      differentiating metastatic from non-metastatic pelvic lymph nodes in patients
      with cervical cancer.

PMID- 24581134
TI  - [A multiple regression formula for the prediction of thyroid microcarcinoma].
AB  - OBJECTIVE: To establish a quantitative analysis formula for the prediction of
      thyroid microcarcinoma and decide the cut-off values for the recommendation of
      ultrasound-guided biopsy. METHODS: The ultrasound characteristics of 830
      subcentimeter thyroid nodules were retrospectively analyzed based on pathological
      results in this study. A diagnostic formula was developed using multivariate
      binary Logistic regression with the cut-off values for the recommendation of
      biopsy. The diagnostic values of each feature and the formula were evaluated.
      RESULTS: The most suspicious ultrasound characteristics for subcentimeter thyroid
      nodules were solid echostructure (OR=41.97), microlobulated margin (OR=25.89),
      hypoechoic echogenicity(OR=10.36), no halo (OR=8.38), irregular margin (OR=4.26),
      taller than wide (OR=2.71), microcalcification (OR=1.92), and macrocalcification
      (OR=1.28). The sensitivity, specificity, and accuracy of the formula were 90.9%,
      54.0%, and 72.5%, respectively. CONCLUSION: This multiple regression formula is
      an objective tool for the evaluation of thyroid microcarcinoma, which can provide
      the cutoff values for the ultrasound guided biopsy.

PMID- 24581135
TI  - [Quantitative T2 mapping evaluates the repaired articular cartilage].
AB  - OBJECTIVE: To evaluate the value of T2 mapping in monitoring the repaired
      cartilage after matrix-associated autologous chondrocyte
      implantation/transplantation (MACI/MACT). METHODS: Four patients (10 plug
      cartilages) were examined three times by T2 mapping at 1, 3, and 6 months using a
      3.0 Tesla MR scan system. Quantitative mean (full-thickness) T2 values were
      calculated in the transplanted area and control cartilage. Paired t-tests were
      used to compare the T2 values between transplanted and control cartilage. For
      analysis of longitudinal T2 values, one-way analyses of variance were performed
      among 1, 3, and 6 months after MACI. RESULTS: The mean T2 values of the
      transplanted area at 1, 3, and 6 months after MACI were (82.40+/-15.23), (71.09+/
      13.06), (53.80+/-4.86) ms, respectively. There were significant differences
      between the transplanted and control cartilage at 1 and 3 months (both P<0.01)
      after MACI, but not at 6 months (P=0.196). There were significant differences
      among T2 values of 1, 3, and 6 months after MACI in transplanted area (P=0.03).
      CONCLUSION: T2 mapping provides a useful tool for monitoring the biochemical
      development of the transplanted cartilage and can be used to evaluate the
      cartilage repair noninvasively.

PMID- 24581136
TI  - [Open construction of experimental abdominal aortic aneurysm swine models with
      Dacron patch for evaluating endovascular aneurysm repair techniques].
AB  - OBJECTIVE: To construct an experimental abdominal aortic aneurysm (AAA) swine
      model with Dacron patch for evaluating endovascular aneurysm repair (EVAR)
      technique. METHODS: The experimental pigs were generally anesthetized for the
      open procedure of an aneurysm model creation with Dacron and subsequent
      arteriography and EVAR with stent graft. Repeat arteriography was performed after
      3-month follow-up. RESULTS: AAA models were successfully constructed in all 10
      experimental pigs. The average aneurysm diameter was (26.3+/-3.1)mm, increasing
      by (15.7+/-3.1)mm comparing to the primary aorta diameter (10.5+/-0.4)mm. The
      aorta diameter before and after the experiment showed significant difference
      (P<0.001). All the animals were survived after the procedure. One swine died 24
      hours after the subsequent EVAR because the covering of both renal arteries by
      the stent graft. The rest 9 animals survived well after the whole operation and 3
      month follow-up. The surviving rates at 1 month and 3 months after the operation
      were both 90%. One type 2 endoleak (10%) was observed after the EVAR, which
      disappeared at 3-month follow-up. CONCLUSIONS: Open construction of experimental
      AAA swine models with Dacron patch is safe and feasible. The model can be used in
      the developing new EVAR techniques and implant training.

PMID- 24581137
TI  - [Comparison of enhanced magnetic resonance imaging and magnetic resonance
      cholangiopancreatography in the differential diagnosis of benign and malignant
      intraductal papillary mucinous neoplasms of the pancreas].
AB  - OBJECTIVE: To compare the value of liver acquisition with volume acceleration
      (LAVA) and magnetic resonance cholangiopancreatography (MRCP) in diagnosing
      benign and malignant intraductal papillary mucinous neoplasms (IPMN) of the
      pancreas. METHODS: The MR findings of 35 IPMN patients confirmed by pathology
      were analyzed retrospectively, and the sequences included T1WI, T2WI, LAVA, and
      MRCP. All patients were divided into two groups: the group of MRI enhancement
      (including T1WI, T2WI, and MRI enhancement) and the group of MRCP (including
      T1WI, T2WI, and MRCP). Two groups were evaluated by the receiver operating
      characteristic (ROC) curve. RESULTS: Totally 23 cases of intraductal papillary
      mucinous tumors and 12 cases of intraductal papillary mucinous carcinomas were
      diagnosed. Finally, 29 cases (29/35) of IPMN were diagnosed correctly in the
      group of MR enhancement, and 25 cases (25/35) diagnosed correctly in the group of
      MRCP. The differential diagnostic accuracy of the group of MRI enhancement
      (82.9%) was higher than that of the group of MRCP (71.4%), although the
      difference was not statistically significant (P=0.068). The sensitivity,
      specificity, positive predictive value, and the area under the ROC curve (AUC) of
      the group of MRI enhancement were 83.3%, 82.6%, 71.4%, and 0.850, and those of
      the group of MRCP were 75.0%, 69.6%, 52.3%, and 0.723. The AUC of the group of
      MRI enhancement was significantly larger than that of the group of MRCP
      (P=0.0465). CONCLUSION: MRI enhancement is more valuable than MRCP in the
      differential diagnosis of benign and malignant IPMN.

PMID- 24581138
TI  - [Endoplasmic reticulum stress and vascular endothelial cell apoptosis].
AB  - Endoplasmic reticulum stress (ERS) is a new pathway of apoptosis following the
      discovery of death receptor signaling pathway and mitochondrial pathway. By
      activating the unfolded protein response (UPR), ERS can suspend protein
      synthesis, restore the endoplasmic reticulum homeostasis, and thus play a
      protective role for cells; however, if the inducing factors of ERS persist, ERS
      will continue to trigger C/EBP homologous protein, JNK, caspase, or other
      pathways to induce apoptosis. In addition, the injury and apoptosis of vascular
      endothelial cells are key links in various diseases and pathophysiologic
      processes, and research has also shown that vascular endothelial cell apoptosis
      is closely related with the ERS. Effective intervention of ERS may restrain
      apoptosis and protect the vascular endothelium. This article reviews the recent
      research advances in ERS and its role in vascular endothelial cell apoptosis.

PMID- 24581139
TI  - [Histone modifications during spermatogenesis and male infertility].
AB  - Many pathological phenomena of male infertility are related to epigenetic changes
      in male germ cells. Epigenetic regulation during spermatogenesis plays an
      important role in mitotic/meiotic divisions and spermiogenesis. The histones have
      various post-translational modifications on different amino acid residues during
      spermatogenesis. These modifications are crucial to the precise regulation of
      spermatogenesis. Moreover, the histone-to-protamine transition will occur during
      spermiogenesis. Many studies have also found that abnormal changes of histone
      modifications during spermatogenesis may damage the sperm development, leading to
      male sterility. This article reviews the changes of histone modifications during
      spermatogenesis, the regulation of the development of male germ cells, and the
      relationship between histone abnormalities and male sterility.

PMID- 24581140
TI  - [Roles of microRNAs in allergic airway diseases].
AB  - The microRNAs (miRNAs/miRs) are a class of short non-coding RNAs regulating
      protein translation via mRNAs silencing. Studies have shown that microRNAs play
      critical roles in allergic diseases, tumors, and infections. The allergic airway
      diseases are characterized by inflammation and hyperresponsiveness of the
      respiratory tract. Several miRNAs are found to be involved in a series of
      pathophysiologic processes in allergic airway diseases including inflammatory
      cells infiltration, cytokines' expressions, airway hyperresponsiveness, and
      proliferation and change in phenotype of smooth muscle cells. Therefore, miRNAs
      may be new therapeutic targets for these allgeric diseases. This article reviews
      the roles of miRNAs in asthma and allergic rhinitis and their molecular
      biological mechanisms.

PMID- 24581142
TI  - Human immunodeficiency virus antibodies and the vaccine problem.
AB  - Despite the great advances made in controlling human immunodeficiency virus type
      1 (HIV-1) infection with antiretroviral drug treatment, a safe and efficacious
      HIV vaccine has yet to be developed. Here, we discuss why clinical trials and
      vaccine development for HIV have so far been disappointing, with an emphasis on
      the lack of protective antibodies. We review approaches for developing
      appropriate HIV immunogens and the stimulation of long-lasting B-cell responses
      with antibody maturation. We conclude that candidate reagents in the pipeline for
      HIV vaccine development are unlikely to be particularly effective. Although the
      major funders of HIV vaccine research and development are placing increasing
      emphasis on clinical product development, a genuine breakthrough in preventing
      HIV infection through vaccines is more likely to come from novel immunogen
      research. 

PMID- 24581141
TI  - Nuclear location of tumor suppressor protein maspin inhibits proliferation of
      breast cancer cells without affecting proliferation of normal epithelial cells.
AB  - BACKGROUND: Maspin, which is classified as a tumor suppressor protein, is
      downregulated in many types of cancer. Several studies have suggested potential
      anti-proliferative activity of maspin as well as sensitizing activity of maspin
      for therapeutic cytotoxic agents in breast cancer tissue culture and animal
      models. All of the experimental data gathered so far have been based on studies
      with maspin localized cytoplasmically, while maspin in breast cancer tumor cells
      may be located in the cytoplasm, nucleus or both. In this study, the effect of
      maspin cytoplasmic and nuclear location and expression level on breast cancer
      proliferation and patient survival was studied. METHODS: Tissue sections from 166
      patients with invasive ductal breast cancer were stained by immunohistochemistry
      for maspin and Ki-67 protein. The localization and expression level of maspin
      were correlated with estimated patient overall survival and percent of Ki-67
      positive cells. In further studies, we created constructs for transient
      transfection of maspin into breast cancer cells with targeted cytoplasmic and
      nuclear location. We analyzed the effect of maspin location in normal epithelial
      cell line MCF10A and three breast cancer cell lines - MCF-7, MDA-MB-231 and SKBR
      3 - by immunofluorescence and proliferation assay. RESULTS: We observed a strong
      positive correlation between moderate and high nuclear maspin level and survival
      of patients. Moreover, a statistically significant negative relationship was
      observed between nuclear maspin and Ki-67 expression in patients with invasive
      ductal breast cancer. Spearman's correlation analysis showed a negative
      correlation between level of maspin localized in nucleus and percentage of Ki-67
      positive cells. No such differences were observed in cells with cytoplasmic
      maspin. We found a strong correlation between nuclear maspin and loss of Ki-67
      protein in breast cancer cell lines, while there was no effect in normal
      epithelial cells from breast. The anti-proliferative effect of nuclear maspin on
      breast cancer cells was statistically significant in comparison to cytoplasmic
      maspin. CONCLUSIONS: Our results suggest that nuclear maspin localization may be
      a prognostic factor in breast cancer and may have a strong therapeutic potential
      in gene therapy. Moreover, these data provide a new insight into the role of
      cytoplasmic and nuclear fractions of maspin in breast cancer.

PMID- 24581143
TI  - Exploring experiences in peer mentoring as a strategy for capacity building in
      sexual reproductive health and HIV service integration in Kenya.
AB  - BACKGROUND: The Integra Initiative designed, tested, and adapted protocols for
      peer mentorship in order to improve service providers' skills, knowledge, and
      capacity to provide quality integrated HIV and sexual and reproductive health
      (SRH) services. This paper describes providers' experiences in mentoring as a
      method of capacity building. Service providers who were skilled in the provision
      of FP or PNC services were selected to undergo a mentorship training program and
      to subsequently build the capacity of their peers in SRH-HIV integration.
      METHODS: A qualitative assessment was conducted to assess provider experiences
      and perceptions about peer mentoring. In-depth interviews were conducted with
      twelve mentors and twenty-three mentees who were trained in SRH and HIV
      integration. Interviews were recorded, transcribed, and imported to NVivo 9 for
      analysis. Thematic analysis methods were used to develop a coding framework from
      the research questions and other emerging themes. RESULTS: Mentorship was
      perceived as a feasible and acceptable method of training among mentors and
      mentees. Both mentors and mentees agreed that the success of peer mentoring
      largely depended on cordial relationship and consensus to work together to
      achieve a specific set of skills. Mentees reported improved knowledge, skills,
      self-confidence, and team work in delivering integrated SRH and HIV services as
      benefits associated with mentoring. They also associated mentoring with an
      increase in the range of services available and the number of clients seeking
      those services. Successful mentorship was conditional upon facility management
      support, sufficient supplies and commodities, a positive work environment, and
      mentors selection. CONCLUSION: Mentoring was perceived by both mentors and
      mentees as a sustainable method for capacity building, which increased providers'
      ability to offer a wide range of and improved access to integrated SRH and HIV
      services.

PMID- 24581144
TI  - Axillary accessory breast tissue--case report and review of literature.

PMID- 24581146
TI  - Study of orientation and penetration of LAH4 into lipid bilayer membranes: pH and
      composition dependence.
AB  - LAH4 is an antimicrobial peptide that is believed to possess both antibiotic and
      DNA delivery capabilities. It is one of a number of membrane-active peptides that
      show increased affinity toward anionic lipids. Herein, we have performed
      molecular dynamics simulations to compare LAH4 effects on anionic palmitoyl
      oleoyl-phosphatidylglycerol bilayer, which approximate a prokaryotic membrane
      environment and zwitterionic palmitoyl-oleoyl-phosphatidylcholine bilayer, which
      approximate a eukaryotic membrane environment. One particular interest in this
      work is to study how different kinds of lipid bilayers respond to the attraction
      of LAH4. Remarkably, our data have shown that the depth of peptide penetration
      strongly depends on membrane composition and pH. At acidic pH, LAH4 has exhibited
      a high tendency to interact strongly with and be adsorbed on anionic membrane. We
      have also shown that electrostatic interactions between His11 and the phosphor
      atoms of bilayers should have a significant impact on the penetration of LAH4.
      These results provide insights into the interactions of LAH4 and lipid bilayers
      at the atomic level, which is useful to understand cell selectivity and mechanism
      of the peptide action. 

PMID- 24581148
TI  - A practical and systematic approach to organisational capacity strengthening for
      research in the health sector in Africa.
AB  - BACKGROUND: Despite increasing investment in health research capacity
      strengthening efforts in low and middle income countries, published evidence to
      guide the systematic design and monitoring of such interventions is very limited.
      Systematic processes are important to underpin capacity strengthening
      interventions because they provide stepwise guidance and allow for continual
      improvement. Our objective here was to use evidence to inform the design of a
      replicable but flexible process to guide health research capacity strengthening
      that could be customized for different contexts, and to provide a framework for
      planning, collecting information, making decisions, and improving performance.
      METHODS: We used peer-reviewed and grey literature to develop a five-step pathway
      for designing and evaluating health research capacity strengthening programmes,
      tested in a variety of contexts in Africa. The five steps are: i) defining the
      goal of the capacity strengthening effort, ii) describing the optimal capacity
      needed to achieve the goal, iii) determining the existing capacity gaps compared
      to the optimum, iv) devising an action plan to fill the gaps and associated
      indicators of change, and v) adapting the plan and indicators as the programme
      matures. Our paper describes three contrasting case studies of organisational
      research capacity strengthening to illustrate how our five-step approach works in
      practice. RESULTS: Our five-step pathway starts with a clear goal and objectives,
      making explicit the capacity required to achieve the goal. Strategies for
      promoting sustainability are agreed with partners and incorporated from the
      outset. Our pathway for designing capacity strengthening programmes focuses not
      only on technical, managerial, and financial processes within organisations, but
      also on the individuals within organisations and the wider system within which
      organisations are coordinated, financed, and managed. CONCLUSIONS: Our five-step
      approach is flexible enough to generate and utilise ongoing learning. We have
      tested and critiqued our approach in a variety of organisational settings in the
      health sector in sub-Saharan Africa, but it needs to be applied and evaluated in
      other sectors and continents to determine the extent of transferability.

PMID- 24581149
TI  - Bulk synthesis of metal-organic hybrid dimers and their propulsion under electric
      fields.
AB  - Metal-organic hybrid particles have great potential in applications such as
      colloidal assembly, autonomous microrobots, targeted drug delivery, and colloidal
      emulsifiers. Existing fabrication methods, however, typically suffer from low
      throughput, high operation cost, and imprecise property control. Here, we report
      a facile and bulk synthesis platform that makes a wide range of metal-organic
      colloidal dimers. Both geometric and interfacial anisotropy on the particles can
      be tuned independently and conveniently, which represents a key advantage of this
      method. We further investigate the self-propulsion of platinum-polystyrene dimers
      under perpendicularly applied electric fields. In 1 * 10(-4) M KCl solution, the
      dimers exhibit both linear and circular motion with the polystyrene lobes facing
      toward the moving direction, due to the induced-charge electroosmotic flow
      surrounding the metal-coated lobes. Surprisingly, in deionized water, the same
      dimers move in an opposite direction, i.e., the metallic lobes face the forward
      direction. This is because of the impact of another type of electrokinetic flow:
      the electrohydrodynamic flow arising from the induced charges on the conducting
      substrate. The competition between the electrohydrodynamic flow along the
      substrate and the induced-charge electroosmotic flow along the metallic lobe
      dictates the propulsion direction of hybrid dimers under electric fields. Our
      synthetic approach will provide potential opportunities to study the combined
      impacts of the geometric and interfacial anisotropy on the propulsion, assembly,
      and other applications of anisotropic particles. 

PMID- 24581147
TI  - Relationship between CT air trapping criteria and lung function in small airway
      impairment quantification.
AB  - BACKGROUND: Small airways are regarded as the elective anatomic site of
      obstruction in most chronic airway diseases. Expiratory computed tomography (CT)
      is increasingly used to assess obstruction at this level but there is no
      consensus regarding the best quantification method. We aimed to evaluate software
      assisted CT quantification of air trapping for assessing small airway obstruction
      and determine which CT criteria better predict small airway obstruction on single
      breath nitrogen test (SBNT). METHODS: Eighty-nine healthy volunteers age from 60
      to 90 years old, underwent spirometrically-gated inspiratory (I) and expiratory
      (E) CT and pulmonary function tests (PFTs) using SBNT, performed on the same day.
      Air trapping was estimated using dedicated software measuring on inspiratory and
      expiratory CT low attenuation area (LAA) lung proportion and mean lung density
      (MLD). CT indexes were compared to SBNT results using the Spearman correlation
      coefficient and hierarchical dendrogram analysis. In addition, receiver operating
      characteristic (ROC) curve analysis was performed to determine the optimal CT air
      trapping criterion. RESULTS: 43 of 89 subjects (48,3%) had dN2 value above the
      threshold defining small airway obstruction (i.e. 2.5% N2/l). Expiratory to
      inspiratory MLD ratio (r = 0.40) and LAA for the range -850 -1024 HU (r = 0.29)
      and for the range -850 -910 HU (r = 0.37) were positively correlated with SBNT
      results. E/I MLD was the most suitable criterion for its expression. Expiratory
      to inspiratory MLD ratio (E/I MLD) showed the highest AUC value (0.733) for small
      airway obstruction assessment. CONCLUSION: Among all CT criteria, all correlating
      with small airway obstruction on SBNT, E/I MLD was the most suitable criterion
      for its expression in asymptomatic subjects with mild small airway obstruction
      TRIAL REGISTRATION: Registered at Clinicaltrials.gov, identifier: NCT01230879.

PMID- 24581150
TI  - Comparative genomics of the Bifidobacterium breve taxon.
AB  - BACKGROUND: Bifidobacteria are commonly found as part of the microbiota of the
      gastrointestinal tract (GIT) of a broad range of hosts, where their presence is
      positively correlated with the host's health status. In this study, we assessed
      the genomes of thirteen representatives of Bifidobacterium breve, which is not
      only a frequently encountered component of the (adult and infant) human gut
      microbiota, but can also be isolated from human milk and vagina. RESULTS: In
      silico analysis of genome sequences from thirteen B. breve strains isolated from
      different environments (infant and adult faeces, human milk, human vagina) shows
      that the genetic variability of this species principally consists of hypothetical
      genes and mobile elements, but, interestingly, also genes correlated with the
      adaptation to host environment and gut colonization. These latter genes specify
      the biosynthetic machinery for sortase-dependent pili and exopolysaccharide
      production, as well as genes that provide protection against invasion of foreign
      DNA (i.e. CRISPR loci and restriction/modification systems), and genes that
      encode enzymes responsible for carbohydrate fermentation. Gene-trait matching
      analysis showed clear correlations between known metabolic capabilities and
      characterized genes, and it also allowed the identification of a gene cluster
      involved in the utilization of the alcohol-sugar sorbitol. CONCLUSIONS: Genome
      analysis of thirteen representatives of the B. breve species revealed that the
      deduced pan-genome exhibits an essentially close trend. For this reason our
      analyses suggest that this number of B. breve representatives is sufficient to
      fully describe the pan-genome of this species. Comparative genomics also
      facilitated the genetic explanation for differential carbon source utilization
      phenotypes previously observed in different strains of B. breve.

PMID- 24581151
TI  - Transcriptional comparison of the filamentous fungus Neurospora crassa growing on
      three major monosaccharides D-glucose, D-xylose and L-arabinose.
AB  - BACKGROUND: D-glucose, D-xylose and L-arabinose are the three major
      monosaccharides in plant cell walls. Complete utilization of all three sugars is
      still a bottleneck for second-generation cellulolytic bioethanol production,
      especially for L-arabinose. However, little is known about gene expression
      profiles during L-arabinose utilization in fungi and a comparison of the genome
      wide fungal response to these three major monosaccharides has not yet been
      reported. RESULTS: Using next-generation sequencing technology, we have analyzed
      the transcriptome of N. crassa grown on L-arabinose versus D-xylose, with D
      glucose as the reference. We found that the gene expression profiles on L
      arabinose were dramatically different from those on D-xylose. It appears that L
      arabinose can rewire the fungal cell metabolic pathway widely and provoke the
      expression of many kinds of sugar transporters, hemicellulase genes and
      transcription factors. In contrast, many fewer genes, mainly related to the
      pentose metabolic pathway, were upregulated on D-xylose. The rewired metabolic
      response to L-arabinose was significantly different and wider than that under no
      carbon conditions, although the carbon starvation response was initiated on L
      arabinose. Three novel sugar transporters were identified and characterized for
      their substrates here, including one glucose transporter GLT-1 (NCU01633) and two
      novel pentose transporters, XAT-1 (NCU01132), XYT-1 (NCU05627). One transcription
      factor associated with the regulation of hemicellulase genes, HCR-1 (NCU05064)
      was also characterized in the present study. CONCLUSIONS: We conducted the first
      transcriptome analysis of Neurospora crassa grown on L-arabinose and performed a
      comparative analysis with cells grown on D-xylose and D-glucose, which deepens
      the understanding of the utilization of L-arabinose and D-xylose in filamentous
      fungi. The dataset generated by this research will be useful for mining target
      genes for D-xylose and L-arabinose utilization engineering and the novel sugar
      transportes identified are good targets for pentose untilization and biofuels
      production. Moreover, hemicellulase production by fungi could be improved by
      modifying the hemicellulase regulator discovered here.

PMID- 24581153
TI  - Application of routine electronic health record databases for pharmacogenetic
      research.
AB  - Inter-individual variability in drug responses is a common problem in
      pharmacotherapy. Several factors (non-genetic and genetic) influence drug
      responses in patients. When aiming to obtain an optimal benefit-risk ratio of
      medicines and with the emergence of genotyping technology, pharmacogenetic
      studies are important for providing recommendations on drug treatments. Advances
      in electronic healthcare information systems can contribute to increasing the
      quality and efficiency of such studies. This review describes the definition of
      pharmacogenetics, gene selection and study design for pharmacogenetic research.
      It also summarizes the potential of linking pharmacoepidemiology and
      pharmacogenetics (along with its strengths and limitations) and provides examples
      of pharmacogenetic studies utilizing electronic health record databases. 

PMID- 24581152
TI  - AGEs breaking and antioxidant treatment improves endothelium-dependent dilation
      without effect on flow-mediated remodeling of resistance arteries in old Zucker
      diabetic rats.
AB  - BACKGROUND: A chronic increase in blood flow in resistance arteries is associated
      with increased lumen diameter (outward remodeling) and improved endothelium (NO)
      mediated relaxation. Flow-mediated remodeling of resistance arteries is essential
      for revascularization in ischemic diseases. Nevertheless, it is impaired in 12 to
      24-month old rats and in young Zucker Diabetic Fatty (ZDF) rats due to advanced
      glycation end products (AGEs) and oxidative stress. As type 2 diabetes occurs
      preferentially in older subjects we investigated flow-mediated remodeling and the
      effect of the AGEs breaker ALT-711 associated or not to the antioxidant TEMPOL in
      one-year old lean (LZ) and ZDF rats. METHODS: Mesenteric resistance arteries were
      exposed to high (HF) or normal blood flow (NF) in vivo. They were collected after
      2 weeks for in vitro analysis. RESULTS: In LZ rats, diameter expansion did not
      occur despite a significant increase in blood flow in HF arteries. Nevertheless,
      endothelium-mediated relaxation was higher in HF than in NF arteries. ALT-711,
      alone or in combination with TEMPOL, restored outward remodeling in HF arteries
      in association with AGEs reduction. TEMPOL alone had no effect. ALT-711, TEMPOL
      or the combination of the 2 drugs did not significantly affect endothelium
      mediated relaxation in HF and NF arteries.In ZDF rats, diameter did not increase
      despite the increase in blood flow and endothelium-mediated relaxation was
      further decreased in HF arteries in association with AGEs accumulation and
      excessive oxidative stress. In both NF and HF arteries, endothelium-mediated
      relaxation was lower in ZDF than in LZ rats. ALT-711, TEMPOL or their combination
      did not improve remodeling (diameter equivalent in HF and NF arteries). In
      parallel, they did not reduce AGEs level and did not improve MMPs activity.
      Nevertheless, ALT-711 and TEMPOL partly improved endothelium-mediated relaxation
      through a reduction of oxidative stress and the association of ALT-711 and TEMPOL
      fully restored relaxation to the level found in LZ rats. CONCLUSIONS: ALT-711 did
      not improve outward remodeling in mature ZDF rats but it reduced oxidative stress
      and consequently improved endothelium-dependent relaxation. In mature LZ rats,
      ALT-711 improved outward remodeling and reduced AGEs level. Consequently, AGEs
      breaking is differently useful in ageing whether it is associated with diabetes
      or not.

PMID- 24581155
TI  - [Thymic tumors preface].

PMID- 24581154
TI  - [Expert consensus on the diagnosis and treatment of bone metastasis in lung
      cancer (2014 version)].

PMID- 24581156
TI  - [The Masaoka-Koga stage classification for thymic malignancies clarification and
      definition of terms].

PMID- 24581157
TI  - [Standard report terms for chest computed tomography reports of anterior
      mediastinal masses suspicious for thymoma].

PMID- 24581158
TI  - [Standard terms, definitions, and policies for minimally invasive resection of
      thymoma].

PMID- 24581159
TI  - [Which way is up? Policies and procedures for surgeons and pathologists regarding
      resection specimens of thymic malignancy].

PMID- 24581160
TI  - [Policies and reporting guidelines for small biopsy specimens of mediastinal
      masses].

PMID- 24581161
TI  - [Radiation therapy definitions and reporting guidelines for thymic malignancies].

PMID- 24581162
TI  - [Chemotherapy definitions and policies for thymic malignancies].

PMID- 24581163
TI  - [Standard outcome measures for thymic malignancies].

PMID- 24581164
TI  - [A review of prognostic factors in thymic malignancies].

PMID- 24581165
TI  - [Bias, biostatistics, and prognostic factors].

PMID- 24581166
TI  - [The mechanism of inhibition effect of adenovirus-mediated ING4 on human lung
      adenocarcinoma xenografts in nude mice].
AB  - BACKGROUND AND OBJECTIVE: The inhibitor of growth 4 (ING4) is an important tumor
      suppressive gene.It has been proven that ING4 could inhibite the proliferation of
      many tumors. e aim of this study is to investigate the inhibitory effect and anti
      cancer mechanism of adenovirus-mediated ING4 gene on SPC-A1 human lung
      adenocarcinoma in nude mice. METHODS: A human lung adenocarcinoma xenograft model
      was established with SPC-A1 cells in nude mice. A total of 15 tumor-bearing nude
      mice were randomly divided into three groups, namely, PBS, Ad-GFP, and Ad-ING4. e
      mice in the three groups were intratumorally injected every other day. Their
      tumor volumes were continually recorded. The treatment tumors were then removed
      from the mice and weighed. Tumor inhibition rates were calculated. Cell apoptosis
      was examined by TUNEL method. Caspase-3, COX-2, Fas, and FasL expressions were
      investigated by immunohistochemistry SP assay. RESULTS: Both tumor weight and
      volume in the Ad-ING4 group were significantly decreased. The tumor inhibition
      rate of the mice in the Ad-ING4 group (33.17% +/- 5.24%) was statistically
      different from that of the mice in the Ad-GFP group (1.31% +/- 0.31%; P<0.05).
      The apoptotic index of the mice in the Ad-ING4 group (69.23% +/- 6.53%) was also
      significantly different from those in PBS (17.04% +/- 1.10%) and Ad-GFP groups
      (18.81% +/- 1.93%; P<0.05). Based on immunohistochemistry SP assay, the results
      showed that Ad-ING4 may not only upregulate the expressions of caspase-3, Fas,
      and FasL but also downregulate the expression of COX-2. CONCLUSION: ING4 gene
      elicited a remarkable growth inhibitory e-ect on human lung adenocarcinoma
      xenografts in nude mice. e mechanism is possibly related to an increase in tumor
      cell apoptosis.

PMID- 24581167
TI  - [The effect and mechanism of vinorelbine on cisplatin resistance of human lung
      cancer cell line A549/DDP].
AB  - BACKGROUND AND OBJECTIVE: Drug resistance is a major obstacle on lung cancer
      treatment and Vinorelbine is an effective drug to inhibition of tumor
      proliferation and metastasis. In this study, we investigated the effect and
      mechanism of Vinorelbine on reversing the cisplatin resistance of human lung
      cancer A549/DDP cell line. METHODS: With 1 MUmol/L and 5 MUmol/L Vinorelbine
      treatment, MTS assay was employed to determine the effect of the cisplatin
      sensitivity of tumor cells, flow cytometry to determine the apoptosis rate and
      change of Rh-123 content; Western blot to determine the expression of MDR1, Bcl
      2, surviving, PTEN, caspase-3/8 and phosphorylation level of Akt (p-Akt); Real
      time PCR was to determine the mRNA expression of MDR1, Bcl-2, survivin and PTEN.
      Finally the transcriptional activities of NF-kappaB, Twist and Snail were
      determined by reporter gene system. RESULTS: With 1 MUmol/L and 5 MUmol/L
      Vinorelbine treatment, the sensitivity of cancer cells to cisplatin was increased
      by 1.91- and 2.54- folds respectively, flow cytometry showed that the content of
      Rh-123 was elevated 1.93- and 2.95- folds and apoptosis rate was increased 2.25-
      and 3.82- folds, Western blot showed that the expression of multidrug resistance
      related proteins MDR, Bcl-2 and survivin were downregulated, caspase-3/8 and PTEN
      was upregulated, phosphorylation of Akt was downregulated as well, real-time
      assay showed that the mRNA expression of MDR1 was downregulated 43.5% and 25.8%,
      Bcl-2 was downregulated 57.3% and 34.1%, survivin was downregulated 37.6% and
      12.4%, PTEN was upregulated 183.4% and 154.2%, the transcriptional activities of
      NF-kappaB was downregulated 53.2% and 34.5%, Twist was downregulated 61.4% and
      33.5%, and Snail was downregulated 57.8% and 18.7%. CONCLUSION: Vinorelbine
      treatment led to increase of cisplatin sensitivity of A549/DDP cells and the
      mechanisms included the regulation of PTEN/AKT/NF-kappaB signal pathway to
      decreased drug resistance gene expression and increased pro-apoptosis gene
      expression.

PMID- 24581168
TI  - [Role of the expression level of Nrf2 in predicting response of EGFR-TKIs in lung
      adenocarcinoma patients with EGFR gene mutations].
AB  - BACKGROUND AND OBJECTIVE: Epidermal growth factor receptor tyrosine kinase
      inhibitors (EGFR-TKIs) have become first-line treatment drugs for lung
      adenocarcinoma patients with EGFR gene mutations. Significant interindividual
      variations in response rate, progression-free survival (PFS), and overall
      survival (OS) have been observed. The expression level of nuclear factor
      erythroid-2-related factor 2 (Nrf2) is related to chemoresistance against
      platinum drugs. Nrf2 overexpression can inhibit the sensitivity of EGFR-TKIs in
      cells with EGFR-sensitive mutations. The aim of this study is to investigate the
      protein expression level of Nrf2 in lung adenocarcinoma patients with EGFR gene
      mutations and to elucidate the correlation between Nrf2 expression and response
      rate of first-line EGFR-TKIs, as well as PFS and OS. METHODS: Immunohistochemical
      analysis of Nrf2 in tumor specimens was performed on 31 patients with stage III
      or IV adenocarcinoma harboring EGFR gene mutations. RESULTS: The Nrf2-positive
      rate was 77.4%, whereas Nrf2 nuclear high-expression rate was 38.7%. The nuclear
      expression level of Nrf2 was significantly correlated with response rate (RR) and
      PFS of EGFR-TKIs (P<0.05), but not with gender, age, smoking, differentiation,
      and OS (P>0.05). The Nrf2-positive level was significantly correlated with PFS
      and OS of EGFR-TKIs (P<0.05), but not with gender, age, smoking, differentiation,
      EGFR gene mutation status, and RR (P>0.05). The PFS and OS of patients with Nrf2
      positive expression were significantly shorter than those in patients with
      negative expression (P<0.05). Furthermore, the nuclear expression level of Nrf2
      was the independent predictive factor for EGFR-TKI-induced PFS, and the Nrf2
      positive level was the independent predictive factor for EGFR-TKI-induced OS
      (P<0.05). CONCLUSIONS: The expression level of Nrf2 is significantly correlated
      with response rate (RR) of EGFR-TKIs, PFS, and OS. Therefore, Nrf2 may be a
      useful biomarker in predicting response of EGFR-TKIs in patients with advanced
      stage lung adenocarcinoma harboring EGFR gene mutations.

PMID- 24581169
TI  - [Survey and analysis of awareness of lung cancer prevention and control in a LDCT
      lung cancer screening project in Tianjin Dagang Oilfield of China].
AB  - BACKGROUND AND OBJECTIVE: It has been proven that increase of the awareness level
      of lung cancer prevention and control could enhance participation of lung cancer
      screening of lung cancer high risk group. The aim of this study is to investigate
      the awareness level of lung cancer prevention and control and the effect of
      individual characteristics on lung cancer awareness, and to provide evidence for
      comprehensive lung cancer prevention in high risk areas of lung cancer. METHODS:
      Staffs of Tianjin Dagang Oil Field who participate low dose CT (LDCT) lung cancer
      screening by cluster sampling or according to voluntary principle were surveyed,
      data of lung cancer awareness were collected by questionnaire. RESULTS: A total
      of 1,633 valid questionnaires were collected. The average age of respondents was
      60.08+/-6.58. Most participants were males (82.2%) while female only accounted
      for 17.8%. The proportions of awareness about lung cancer in China, risk factors,
      screening methods and the knowledge of health examination were 64.5%, 77.1%,
      43.7%, 49.6% respectively. Result of multiple logistic regression analysis showed
      that education level, smoking (pack-year), age, prior tuberculosis were the
      influencing factors of lung cancer awareness with adjusted Ors for education and
      age level as of 0.567 (95%CI: 0.439-0.733) and 1.373 (95%CI: 1.084-1.739)
      respectively. 80.3% of the participants can accept health examination once a
      year, while the ability to pay the medical expenses was not high. The influencing
      factors of health examination willingness were gender, age, income, the knowledge
      of lung cancer. CONCLUSIONS: Education level and smoking affect the awareness of
      lung cancer prevention and control, health education for lung cancer should be
      conducted especially in population with low education level. Comprehensive lung
      cancer control in high risk areas should combined lung cancer screening, tobacco
      control and health education.

PMID- 24581170
TI  - [The application of mediastinoscopy in the differential diagnosis and
      preoperative staging on lung cancer].
AB  - BACKGROUND AND OBJECTIVE: To discuss the clinical application of mediastinoscopy
      in the differential diagnosis and preoperative staging on lung cancer. METHODS: A
      total of 361 cases of patients were included in the study, of which 162 cases
      were undiagnosed mediastinal tumor patients before operation, and 199 patients
      were suspected or diagnosed with lung cancer or mediastinal lymph nodes
      enlargment(short diameter >=1.0 cm). All patients underwent surgery, including
      308 cases standard cervical mediastinoscopy (SCM) , 53 cases parasternal
      mediastinoscopy (PM). RESULTS: Taking pathology diagnosis as the gold standard,
      the mediastinoscopy diagnostic accuracy, sensitivity, specificity, positive
      predictive value, negative predictive value are 98.11%, 97.62%, 100%, 100%,
      91.67% and 98.28%, 98.03%, a 100%, 100%, 100% to mediastinal masses and
      mediastinal lymph node metastasis of lung cancer. Total seven cases suffered from
      complications of surgery-related, the complication rate was 1.93 percent
      (P<0.05). CONCLUSIONS: The trauma of the mediastinoscopy is slight, which is
      safe, reliable, able to take in sufficient tissue quantities. Mediastinoscopy is
      highly helpful not only in diagnostic of mediastinal mass, but also in the
      differential diagnosis of lung cancer, and it's an important method and the gold
      standard of preoperative staging on lung cancer.

PMID- 24581171
TI  - Bufalin attenuates the stage and metastatic potential of hepatocellular carcinoma
      in nude mice.
AB  - BACKGROUND: Advanced hepatocellular carcinoma (HCC) patients undergo significant
      tumor growth and metastasis. Here, we investigated bufalin for treating HCC,
      which exhibits anti-tumor activities in many tumor cell lines. METHOD: In our
      experiment, HCCLM3-R cells were injected into nude mice to form subcutaneous
      human HCC tumors that were implanted into the liver to establish orthotopic
      transplantation tumor models. Bufalin was injected intraperitoneally at 1 or 1.5
      mg/kg. LY294002 (100 mg/kg), a potent inhibitor of Akt which reduced the levels
      of pAkt in HCCLM3 cell lines, was injected intraperitoneally into one group
      thrice weekly. The control was injected with an equal volume of saline.
      Morphological alterations were evaluated in the liver and lung by
      stereomicroscopy, the apoptotic rate was measured by TUNEL staining, and
      expression of AKT/GSK3beta/beta-catenin/E-cadherin signaling pathway-related
      proteins was detected by immunohistochemistry (IHC) and western blot analysis.
      RESULTS: These results suggested that the sizes and qualities of orthotopic
      transplanted tumors as well as pulmonary metastasis decreased markedly at the
      highest bufalin dose compared with that in the control. Orthotopic transplanted
      tumor tissues were necrotic in bufalin-treated groups and the apoptotic cell
      number was markedly higher at the highest bufalin dose compared with that in the
      control. Certain changes of expression of AKT/GSK3beta/beta-catenin/E-cadherin
      signaling pathway-related proteins were in tumor tissues, which were related to
      the bufalin dose. Similar results were observed in the LY294002-treated group.
      CONCLUSION: Based on the above, one can draw conclusions that bufalin has
      significant anti-tumor activities and reduces the metastatic potential in an
      orthotopic transplantation tumor model of human HCC. Inhibition of
      AKT/GSK3beta/beta-catenin/E-cadherin signaling pathways by bufalin may show
      therapeutic effects in advanced HCC patients.

PMID- 24581172
TI  - Motor control strategies during double leg squat following anterior cruciate
      ligament rupture and reconstruction: an observational study.
AB  - BACKGROUND: Anterior cruciate ligament (ACL) injured individuals often show
      asymmetries between the injured and non-injured leg. A better understanding of
      the underlying motor control could help to improve rehabilitation. Double leg
      squat exercises allow for compensation strategies. This study therefore
      investigated motor control strategies during a double leg squat with the aim to
      investigate if individuals with ACL rupture (ACLD), ACL reconstruction (ACLR) and
      healthy control subjects (CONT) used different strategies. METHODS: 20 ACLD and
      21 ACLR were compared to 21 CONT subjects. Participants performed eight
      continuous double leg squats to their maximum depth, while kinematic and kinetic
      data were collected. Outcome measures were calculated to quantify the behavior of
      the injured and non-injured legs and the asymmetry between these legs. RESULTS:
      Squat depth was significantly reduced in ACLR and ACLD compared to CONT (p <
      0.05; 106 +/- 17 degrees ; 105 +/- 21 degrees ; 113 +/- 21 degrees ). Peak knee
      extensor moments (Mkn(mx)) were significantly reduced in ACLR and ACLD compared
      to CONT in the injured leg only (p < 0.05; 0.045 +/- 0.015; 0.046 +/- 0.016;
      0.059 +/- 0.022 body weight.height respectively). There was no significant
      correlation between symmetry of the support moment (SYM(Msup)) and of the %
      support moment by the knee (SYM%supkn) in CONT (R(2) = -0.07). Data distribution
      average indicated good symmetry. ACLR showed a significant correlation between
      SYM(Msup) and SYM%sup(kn) (R(2) = 0.561) when two participants who did not
      recover as well were excluded. ACLR controlled knee moment magnitude using two
      strategies; 1) transfer of support moment to non-injured leg; 2) transfer of
      support moment from knee to ankle and/or hip of injured leg. These were combined
      in different proportions, but with the same effect on the knee moment. ACLD
      showed no significant correlation between SYM(Msup) and SYM%sup(kn) (R(2) =
      0.015). Data distribution average indicated reduced symmetry. ACLD therefore used
      an avoidance strategy: reducing squat depth and subsequently the support moment
      in the injured leg and the knee contribution. CONCLUSIONS: ACLD and ACLR
      individuals used different squatting strategies compared to controls, with ACLR
      using controlled and ACLD using avoidance behavior regarding knee loading. This
      has major implications for rehabilitation as these kinetic strategies cannot be
      observed, but result in the injured leg not being exercised as intended.

PMID- 24581173
TI  - Bronchoscopic intratumoral injection of tranexamic acid to prevent excessive
      bleeding during multiple forceps biopsies of lesions with a high risk of
      bleeding: a prospective case series.
AB  - BACKGROUND: Significant bleeding may occur following endobronchial forceps biopsy
      or brushing of necrotic or hypervascular tumors in the airways. In some cases,
      methods such as endobronchial instillation of iced saline lavage and epinephrine
      may fail to control bleeding. The present study evaluated the efficacy and safety
      of a new bronchoscopic technique using intratumoral injection of tranexamic acid
      (IIT) for control of bleeding during forceps biopsy in patients with
      endobronchial tumors with a high risk of bleeding. METHODS: The study was a
      prospective case series carried out in a single center. Bronchoscopic IIT was
      performed in those patients who had endoscopically visible tumoral lesions with
      persistent active bleeding following the first attempt at bronchoscopic sampling.
      Tranexamic acid (TEA) was injected through a 22-gauge Wang cytology needle into
      the lesion in nominal doses of 250-500 mg. After 2-3 minutes, multiple forceps
      biopsy specimens were obtained from the lesion. RESULTS: Of the 57 consecutive
      patients included in the study, 20 patients (35.1%) underwent bronchoscopic IIT.
      The first attempt in 18 patients was endobronchial forceps biopsy (EBB), and
      because of a high risk of bleeding, the first attempt for the remaining two
      patients, who were on continuous dual antiplatelet therapy (aspirin and
      clopidogrel), employed endobronchial needle aspiration (EBNA) as a precautionary
      measure. Following IIT, subsequent specimens were obtained using EBB in all
      patients. Multiple forceps biopsy specimens (3-10) were obtained from the lesions
      (8 necrotic and 12 hypervascular) without incurring active bleeding. The
      following histopathologic diagnoses were made: squamous cell carcinoma (n = 14),
      adenocarcinoma (n = 2), small-cell lung cancer (n = 3), and malignant mesenchymal
      tumor (n = 1). No side effects of TEA were observed. CONCLUSIONS: Bronchoscopic
      IIT is a useful and safe technique for controlling significant bleeding from a
      forceps biopsy procedure and can be considered as a pre-biopsy injection for
      lesions with a high risk of bleeding. TRIAL REGISTRATION: ISRCTN23323895.

PMID- 24581174
TI  - Design, synthesis, and preliminary cardioprotective effect evaluation of
      danshensu derivatives.
AB  - A series of (R)-3,4-dihydroxyphenyllactic acid Danshensu (DSS) derivatives were
      synthesized, and their cardioprotective effects were evaluated in vitro and in
      vivo. Among the new derivatives, compound 14 showed significant protective
      effects in cultured myocardial cells and in the rat model of myocardial ischemia.
      The therapeutic efficacy of compound 14 was significantly higher than that of its
      parent compound DSS, and amlodipine, a first-line treatment for angina pain.
      Compound 14 potently scavenged free radicals, significantly decreased the levels
      of LDH and MDA, and inhibited the leakage of CK in animal model of ischemia. We
      had previously found that compound 14 activated PI3K/Akt/GSK-3beta and
      Nrf2//Keap1/heme oxygenase-1 (HO-1) signaling pathways in H9c2 cells. These
      results suggest that compound 14 has a unique mechanism of action, that is,
      multifunctional. Compound 14 may be a new potential therapy for ischemic heart
      diseases. 

PMID- 24581175
TI  - Clinical results for use of local anesthesia with epinephrine in penile nerve
      block.
AB  - BACKGROUND: It is widely accepted that local anesthetics with epinephrine should
      not be used in areas served by terminal vessels. There is no evidence in studies
      for this in penile surgery, and given the anatomy of the penis, perfusion
      complications are highly unlikely. The goal of this study was to show that a
      penile block using a local anesthetic with epinephrine is safe. PATIENTS AND
      METHODS: In a follow-up study between 2005 and 2010, we analyzed 95 patients who
      got a penile ring block with subcutaneous infusion anesthesia (SIA). The SIA
      solution consisted of ropivacaine and lidocaine (0.11% and 0.21%) plus
      epinephrine. RESULTS: There were no anesthetic complications. Short-term negative
      postoperative occurrences (<72 hrs.) were swelling (42%), problems with suture
      material (22%), pain (19%), hematoma and paresthesia (each 13%), erectile
      dysfunction (12%), small-area skin necrosis after wound healing without requiring
      further surgery (13%), micturition disorders (7%), and wound infection (6%). Two
      patients on anticoagulation therapy had postoperative bleeding requiring revision
      surgery. 5% of the patients were given further analgesic sedation. 19% complained
      about postoperative pain. Persistent complaints (maximum 6 months) were
      disturbances of skin sensation (7%), swelling (4%), and redness and micturition
      disorders (3% each). CONCLUSIONS: Supplementing a local anesthetic with
      epinephrine in penis operations has many advantages, including high patient
      satisfaction, relatively painless infiltration, low complication rates, improved
      view of the operating field, and an extended effect of anesthetics with a
      prolonged reduction in pain. Because of the anatomy of the organ, there is no
      risk of necrosis related to using a subcutaneous penile ring block. Thus the view
      that epinephrine should not be used in penis procedures is obsolete.

PMID- 24581176
TI  - Genome-wide distribution of genetic diversity and linkage disequilibrium in a
      mass-selected population of maritime pine.
AB  - BACKGROUND: The accessibility of high-throughput genotyping technologies has
      contributed greatly to the development of genomic resources in non-model
      organisms. High-density genotyping arrays have only recently been developed for
      some economically important species such as conifers. The potential for using
      genomic technologies in association mapping and breeding depends largely on the
      genome wide patterns of diversity and linkage disequilibrium in current breeding
      populations. This study aims to deepen our knowledge regarding these issues in
      maritime pine, the first species used for reforestation in south western Europe.
      RESULTS: Using a new map merging algorithm, we first established a 1,712 cM
      composite linkage map (comprising 1,838 SNP markers in 12 linkage groups) by
      bringing together three already available genetic maps. Using rigorous
      statistical testing based on kernel density estimation and resampling we
      identified cold and hot spots of recombination. In parallel, 186 unrelated trees
      of a mass-selected population were genotyped using a 12k-SNP array. A total of
      2,600 informative SNPs allowed to describe historical recombination, genetic
      diversity and genetic structure of this recently domesticated breeding pool that
      forms the basis of much of the current and future breeding of this species. We
      observe very low levels of population genetic structure and find no evidence that
      artificial selection has caused a reduction in genetic diversity. By combining
      these two pieces of information, we provided the map position of 1,671 SNPs
      corresponding to 1,192 different loci. This made it possible to analyze the
      spatial pattern of genetic diversity (He) and long distance linkage
      disequilibrium (LD) along the chromosomes. We found no particular pattern in the
      empirical variogram of He across the 12 linkage groups and, as expected for an
      outcrossing species with large effective population size, we observed an almost
      complete lack of long distance LD. CONCLUSIONS: These results are a stepping
      stone for the development of strategies for studies in population genomics,
      association mapping and genomic prediction in this economical and ecologically
      important forest tree species.

PMID- 24581179
TI  - Transgenic expression of delta-6 and delta-15 fatty acid desaturases enhances
      omega-3 polyunsaturated fatty acid accumulation in Synechocystis sp. PCC6803.
AB  - BACKGROUND: Polyunsaturated fatty acids (PUFAs), which contain two or more double
      bonds in their backbone, are the focus of intensive global research, because of
      their nutritional value, medicinal applications, and potential use as biofuel.
      However, the ability to produce these economically important compounds is
      limited, because it is both expensive and technically challenging to separate
      omega-3 polyunsaturated fatty acids (omega-3 PUFAs) from natural oils. Although
      the biosynthetic pathways of some plant and microalgal omega-3 PUFAs have been
      deciphered, current understanding of the correlation between fatty acid
      desaturase content and fatty acid synthesis in Synechocystis sp. PCC6803 is
      incomplete. RESULTS: We constructed a series of homologous vectors for the
      endogenous and exogenous expression of Delta6 and Delta15 fatty acid desaturases
      under the control of the photosynthesis psbA2 promoter in transgenic
      Synechocystis sp. PCC6803. We generated six homologous recombinants, harboring
      various fatty acid desaturase genes from Synechocystis sp. PCC6803, Gibberella
      fujikuroi and Mortierella alpina. These lines produced up to 8.9 mg/l of alpha
      linolenic acid (ALA) and 4.1 mg/l of stearidonic acid (SDA), which are more than
      six times the corresponding wild-type levels, at 20 degrees C and 30 degrees C.
      Thus, transgenic expression of Delta6 and Delta15 fatty acid desaturases enhances
      the accumulation of specific omega-3 PUFAs in Synechocystis sp. PCC6803.
      CONCLUSIONS: In the blue-green alga Synechocystis sp. PCC6803, overexpression of
      endogenous and exogenous genes encoding PUFA desaturases markedly increased
      accumulation of ALA and SDA and decreased accumulation of linoleic acid and gamma
      linolenic acid. This study lays the foundation for increasing the fatty acid
      content of cyanobacteria and, ultimately, for producing nutritional and medicinal
      products with high levels of essential omega-3 PUFAs.

PMID- 24581180
TI  - Suppression of autophagy by chloroquine sensitizes 5-fluorouracil-mediated cell
      death in gallbladder carcinoma cells.
AB  - Autophagy1 is a complex of adaptive cellular response that enhances cancer cell
      survival in the face of cellular stresses such as chemothery. Here we show that
      in human gallbladder carcinoma (GBC) cells lines, SGC-996 and GBC-SD, autophagy
      is induced by the DNA damaging agent 5-fluorouracil (5-FU). While in combination
      with the pre-treatment of chloroquine (CQ), a inhibitor of autophagy, the
      inhibition of 5-FU to the proliferation and viability of GBC cells was
      potentiated. Furthermore, 5-FU treatment resulted in a general increase of the
      apoptotic rate and G0/G1 arrest of GBC cells, and the effect was potentiated by
      CQ pre-treatment. Since 5-FU induced autophagy in GBC cells, and CQ inhibited
      autophagy, our findings suggest a possible mechanism that CQ inhibited 5-FU
      induced autophagy, which modified the cytotoxicity of 5-FU. The combination
      therapy of CQ and 5-FU should be considered as an effective strategy for the
      treatment of gallbladder carcinoma. 

PMID- 24581181
TI  - Potential prognostic value of biomarkers in lavage, sputum and serum in a five
      year clinical follow-up of smokers with and without COPD.
AB  - BACKGROUND: The aim of this study was to test whether repeatable biomarkers
      collected from serum, bronchoalveolar lavage (BAL) and sputum of healthy smokers
      and smokers with COPD would have a prognostic value with respect to the decline
      in lung function over a 5 year period. METHODS: In 2006/2007 we had repeatedly
      collected serum, BAL and sputum of 23 healthy smokers and 24 smokers with COPD
      (GOLD II) and analysed a panel of more than 100 different parameters. In 2012 we
      reinvited these subjects to assess the change in lung function to enable the
      investigation of the potential prognostic value of the 2006/2007 markers and to
      determine the long-term repeatability of selected blood and serum markers. In
      this follow-up study we performed body-plethysmography, a blood gas analysis and
      collected blood and urine samples. The change in lung function was compared with
      67 markers from BAL, sputum, serum and whole blood that were shown in the
      2006/2007 assessment to be repeatable over a 6 week period. RESULTS: We were able
      to recruit 13 (54%) smokers with COPD and 11 (48%) former healthy smokers that
      participated in the 2006/2007 study. The decline in lung function was larger in
      COPD smokers; five of them changed to GOLD III, one to GOLD IV. Two healthy
      smokers changed to GOLD I. Blood cells, serum von Willebrand factor and alpha-1
      antitrypsin showed a good repeatability over 5 years. In COPD smokers a weak
      correlation between 2006/2007 sputum markers of neutrophilic inflammation and the
      5 year change in FEV1/FVC was found. CONCLUSIONS: Our data suggests that inter
      individual and group differences are maintained over a five year period. Despite
      the large panel of markers available for this analysis, a potential prognostic
      value appears to exist only for some sputum inflammatory markers. If these data
      can be confirmed in larger COPD cohorts, it would emphasize the value of sputum
      markers in clinical trials and support the assumption that an anti-inflammatory
      treatment can have long term benefits in COPD.

PMID- 24581182
TI  - Is age-related macular degeneration a manifestation of systemic disease? New
      prospects for early intervention and treatment.
AB  - Age-related macular degeneration (AMD) is a common vision-threatening condition
      affecting the elderly. AMD shares common risk factors and processes, including
      vascular and inflammatory pathways, with many systemic disorders. Associations
      have been reported between AMD and hypertension, cardiovascular disease,
      cerebrovascular disease, dyslipidaemia, chronic kidney disease and
      neurodegenerative disorders. An increasing amount of evidence suggests that
      individuals with AMD are also at risk of systemic diseases such as stroke. In
      this review, we summarize the latest evidence to support the notion that AMD is
      an ocular manifestation of systemic disease processes, and discuss the potential
      systemic side effects of ocular AMD therapy of which general physicians should be
      aware. Recent genetic discoveries and understanding of the pathogenic pathways in
      AMD in relation to systemic disorders are also highlighted. 

PMID- 24581183
TI  - Androgen receptor CAG repeats, non-random X chromosome inactivation, and loss of
      heterozygosity at Xq25 in relation to breast cancer risk.
AB  - BACKGROUND: The aim of this study was to examine the association of non-random X
      chromosome inactivation (XCI) and loss of heterozygosity (LOH) at Xq25 with
      breast cancer development. METHODS: Seventy-nine breast cancer patients, 39
      female lung cancer patients, 30 other cancer patients and 77 healthy females were
      analysed for LOH using a panel of 11 microsatellite markers spanning Xq25. The
      androgen receptor (AR) gene was chosen as an XCI marker. RESULTS: LOH of at least
      one microsatellite locus at Xq25 was identified in 46/65 breast cancers examined,
      while only 10/25 cancers of other origins demonstrated LOH in this region (p =
      0.014). The critical deletion region in breast cancer was around marker DXS1047
      (47.23%). Moreover, we found that tissues from eight breast cancers showed LOH at
      all of the informative loci tested at Xq25, while the other 38 showed partial
      (interstitial or telomeric) alterations at Xq25. Interestingly, the pattern of
      XCI of these eight breast cancers tended to be non-random. We estimated the
      frequencies of AR alleles and found that women with two long AR alleles (>=21 CAG
      repeats) had an increased risk of developing breast cancer, while those with two
      short AR alleles (<21 CAG repeats) were likely to be normal (p = 0.00069).
      CONCLUSIONS: The extraordinary high frequencies of LOH at Xq25 found in this
      study strongly imply that there might be one or more tumour suppressor genes
      (TSGs) related to the development of breast cancer at Xq25 in the Taiwanese
      female population.

PMID- 24581185
TI  - [Analysis of the Cochrane review: Multimedia educational interventions for
      consumers about prescribed and over-the-counter medications. Cochrane Database of
      Systematic Reviews 2013;4:CD008416].
AB  - Understanding of the relevant information is especially important in the area of
      drug treatment, to guarantee an appropriate and rational use of medications by
      patients. The relevant information must be delivered in a way that patients
      understand all aspects of the treatment regimen they are taking. In this
      systematic review the authors analyzed a set of studies on the effectiveness of
      multimedia educational interventions about medications (prescribed or not) in
      patients of all ages, concluding that the aforementioned interventions are more
      effective than usual care (non-standardized education provided by health
      professionals as part of usual clinical care) or no education. 

PMID- 24581184
TI  - [Think tank: strategic report on the scientific biomedical publication in
      Portugal].

PMID- 24581186
TI  - [From England to Portugal: lessons to be learned about palliative care].

PMID- 24581187
TI  - [Lung cancer mortality].

PMID- 24581188
TI  - [Prostate cancer: are we able to diagnose those in need? And are those that are
      diagnosed and treated those that are effectively in need?].

PMID- 24581189
TI  - [Diabetes mellitus and its influence on the success of endodontic treatment: a
      retrospective clinical study].
AB  - INTRODUCTION: Diabetes mellitus is an endocrine disease in which are involved the
      hormones produced by the islets of Langerhans. The diabetes mellitus can affect
      various functions of the immune system of the individual, predisposing them to
      chronic inflammation, progressive degradation of tissues and decreased tissue
      repair. The changes caused by this disease at the level of the oral cavity can
      highlight xerostomia, dysgeusia, periodontal alterations, increased
      susceptibility to infection and changes both in the dental pulp and periapical
      tissues. OBJECTIVES: The aim of this study is to evaluate the influence of
      diabetes mellitus at the periapical tissues and the success of endodontic
      treatment in these patients. MATERIAL AND METHODS: We analyzed 737 cases treated
      in consultation Area of Dental Medicine, which were made nonsurgical endodontic
      treatments, between the years 2003 and 2012. These were selected patients with
      diabetes mellitus, a total of 32, of whom 23 were willing to come to the
      consultation and to participate in this study. The data collected were analyzed
      using the Statistical Package for the Social Sciences, version 19, at a
      significance level of 5%. RESULTS: A total of 37 teeth in the test group and 25
      in the control group. For the analyzed parameters related to the diagnosis pulp,
      mobility, fistula, pain on percussion horizontal and vertical evaluation of final
      restoration and the time interval between the query and the final restoration
      shutter and / or the control visit, there were no differences statistically
      significant (p > 0.05). Regarding the assessment of the success of endodontic
      treatment, this was 62% in the test group and 80% in the control group (p >
      0.05). CONCLUSIONS: The results of this study are inconclusive regarding the
      increasing prevalence of apical periodontitis in diabetic patients. Regarding the
      evaluation of the success of endodontic treatments examined it was found that the
      success rate in diabetic patients is lower, though not statistically significant.
      For this reason and given the limitations of this study, we cannot state that
      patients with diabetes mellitus have a greater predisposition to the development
      of periradicular lesions or that the success of endodontic treatment in these
      patients is compromised. It is important, however, that further studies are
      developed to characterize the pulp and periradicular changes and to assess the
      prevalence of apical periodontitis and progression in patients with diabetes
      mellitus.

PMID- 24581190
TI  - [European Portuguese EARS test battery adaptation].
AB  - INTRODUCTION: The use of adequate assessment tools in health care is crucial for
      the management of care. The lack of specific tools in Portugal for assessing the
      performance of children who use cochlear implants motivated the translation and
      adaptation of the EARS (Evaluation of Auditory Responses to Speech) test battery
      into European Portuguese. This test battery is today one of the most commonly
      used by (re)habilitation teams of deaf children who use cochlear implants
      worldwide. The goal to be achieved with the validation of EARS was to provide
      (re)habilitation teams an instrument that enables: (i) monitoring the progress of
      individual (re)habilitation, (ii) managing a (re)habilitation program according
      to objective results, comparable between different (re)habilitation teams, (iii)
      obtaining data that can be compared with the results of international teams, and
      (iv) improving engagement and motivation of the family and other professionals
      from local teams. MATERIAL AND METHODS: For the test battery translation and
      adaptation process, the adopted procedures were the following: (i) translation of
      the English version into European Portuguese by a professional translator, (ii)
      revision of the translation performed by an expert panel, including doctors,
      speech-language pathologists and audiologists, (iii) adaptation of the test
      stimuli by the team's speechlanguage pathologist, and (iv) further review by the
      expert panel. RESULTS: For each of the tests that belong to the EARS battery, the
      introduced adaptations and adjustments are presented, combining the
      characteristics and objectives of the original tests with the linguistic and
      cultural specificities of the Portuguese population. DISCUSSION: The difficulties
      that have been encountered during the translation and adaptation process and the
      adopted solutions are discussed. Comparisons are made with other versions of the
      EARS battery. CONCLUSION: We defend that the translation and the adaptation
      process followed for the EARS test battery into European Portuguese was correctly
      conducted, respecting the characteristics of the original instruments and
      adapting the test stimuli to the linguistic and cultural reality of the
      Portuguese population, thus meeting the goals that have been set.

PMID- 24581191
TI  - [Patient satisfaction with anesthesia care in a general hospital].
AB  - INTRODUCTION: The satisfaction level with health care reflects the quality of
      care from the patient's perspective. The aim of this study is to assess patient
      satisfaction with anesthesia care in a Portuguese general hospital by using the
      "The Heidelberg Peri-anaesthetic Questionnaire". MATERIAL AND METHODS: The
      questionnaire was translated and tested based on psychometric quality criteria in
      a sample of 107 patients who underwent elective surgery as inpatients at Hospital
      de Sao Joao. The global satisfaction and for each dimension of care were
      calculated. We analyzed the differences between patients with different levels of
      satisfaction, identifying potential confounding factors. RESULTS: The Portuguese
      version of the questionnaire has 32 items distributed in three dimensions:
      'staff', 'discomfort' and 'fear'. The mean values of satisfaction for each
      dimension were 83.4%, 66.8% and 65.9%, respectively. The internal consistence was
      demonstrated by a Cronbach's alpha coefficient ranging from 0.776 to 0.875 in the
      three dimensions. Satisfied and dissatisfied patients differed in the three
      dimensions, but to a lesser degree in 'staff'. In the multivariate analysis we
      found significant influence of gender in the 'discomfort' dimension. DISCUSSION:
      The questionnaire has good psychometric characteristics. The domain 'staff'
      includes three domains of the source questionnaire. CONCLUSIONS: Its application
      revealed high satisfaction levels regarding the staff. Dissatisfaction was mainly
      seen in the "fear" and "discomfort" dimensions, the latter being significantly
      lower in males.

PMID- 24581192
TI  - [Prevalence of chromosomal abnormalities in spontaneous abortions or fetal
      deaths].
AB  - INTRODUCTION: Spontaneous abortion is one of the most frequent problems of
      pregnancy, estimated to affect, at least, one in every four women who tries to
      conceive. The main purpose of this work was to study the prevalence of
      chromosomal abnormalities in gestational losses, evaluating their relation with
      maternal age, gestational age and previous abortion history. MATERIAL AND
      METHODS: Retrospective study of 401 pregnancy loss cases that have gone through
      cytogenetic and anatomopathologic analysis between January 2008 and June 2012, in
      Centro Hospitalar de S. Joao, Oporto. RESULTS: Of the 401 cases sent to
      cytogenetic study, it was possible to obtain information about the chromosomal
      complement in 333 cases, of which 72.7% showed normal karyotype, and 27.3%
      abnormal karyotype. Aneuploidies represented 92.3% of the identified
      chromosomopathies, with trisomies being the most frequent, related with an
      advanced maternal age and an early gestational age. There was no agreement
      between the results of the cytogenetic and the anatomopathologic analysis.
      DISCUSSION/CONCLUSION: The prevalence of chromosomal abnormalities, during the
      first trimester, is similar between sporadic and recurrent miscarriages. With
      increased maternal age, trisomies, the most frequent type of aneuploidy, are more
      likely to occur, with a mean increment in probability of 7.4% per year. A
      significant karyotype-pathological correlation was not established. Maternal
      contamination is the main obstacle to the accurate determination of the
      prevalence of chromosomal abnormalities. The molecular cytogenetic techniques
      already available can overcome the limitations of the conventional technique.

PMID- 24581193
TI  - [Evaluation of antiangiogenic treatment results in choroidal neovascularization
      related to pathological myopia].
AB  - INTRODUCTION: Choroidal neovascularization secondary to pathological myopia is
      one of the leading causes of irreversible central vision loss in younger
      patients. The purposes of our study is to evaluate the long-term results of
      antiangiogenic treatment, with ranibizumab and/or bevacizumab, in myopic
      choroidal neovascularization and define the predictive factors for visual and
      anatomic outcomes. MATERIAL AND METHODS: In this study were included 84 eyes from
      81 patients with myopic choroidal neovascularization. Eighty-four (100%) eyes
      accomplish 12 months of follow-up, 67 (79.8%) 24 months, 54 (64.3%) 36 months, 29
      (34.5%) 48 months, and 15 (16.7%) 60 months. We retrieved data related to best
      corrected visual acuity measured with ETDRS chart, foveal center thickness on
      optical coherence tomography and fluorescein angiographic findings, before and
      after treatment. RESULTS: The best corrected visual acuity and foveal center
      thickness improvements were statistically significant for all follow-up times (p
      < 0.05). Mean baseline best corrected visual acuity was 43.7 +/- 20.1 letters and
      mean baseline foveal center thickness was 304.8 +/- 127.9 um. Mean best corrected
      visual acuity was 55.6 +/- 18.5, 52.1 +/- 22.3, 52.1 +/- 22.6, 50.3 +/- 23.8 and
      47.8 +/- 24.5 for 12, 24, 36, 48 and 60 months of treatment, respectively. Mean
      foveal center thickness was 209.7 +/- 86.2, 190.6 +/- 76.1, 174.7 +/- 60.6, 189.8
      +/- 96.7 and 159.4 +/- 73.3 for the same follow-up times. Baseline best corrected
      visual acuity was the only predictive factor for better visual outcome (p <
      0.001). DISCUSSION/CONCLUSION: Intravitreal anti-VEGF injections in patients with
      myopic choroidal neovascularization yielded a significant and sustained
      functional and anatomic improvement. Randomized long-term clinical trials are
      needed to determine the sustained efficacy of these drugs.

PMID- 24581194
TI  - [Fractional exhaled nitric oxide in monitoring and therapeutic management of
      asthma].
AB  - INTRODUCTION: Asthma is a chronic respiratory disease characterized by hyper
      responsiveness and bronchial inflammation. The bronchial inflammation in these
      patients can be monitored by measuring the fractional exhaled nitric oxide. This
      study aims to determine fractional exhaled nitric oxide association with peak
      expiratory flow and with asthma control inferred by the Global Initiative for
      Asthma. MATERIAL AND METHODS: Observational, analytical and cross-sectional study
      of children with asthma, 6-12 years-old, followed in the Outpatient Respiratory
      Pathology of Braga Hospital. Sociodemographic and clinical information were
      collected through a questionnaire. fractional exhaled nitric oxide and peak
      expiratory flow were determined by portable analyzer Niox Mino(r) and flow meter,
      respectively. RESULTS: The sample is constituted by 101 asthmatic children, 63
      (62.4%) of males and 38 (37.6%) females. The mean age of participants in the
      sample is 9.18 (1.99) years. The logistic regression performed with the cutoff
      value obtained by ROC curve, revealed that fractional exhaled nitric oxide
      (b(FENO classes) = 0.85; chi(2)Wald (1) = 8.71; OR = 2.33; p = 0.003) has a
      statistical significant effect on the probability of changing level of asthma
      control. The odds ratio of going from "controlled" to "partly
      controlled/uncontrolled" is 2.33 per each level of fractional exhaled nitric
      oxide. DISCUSSION: The probability of an asthmatic children change their level of
      asthma control, from 'controlled' to 'partly controlled/uncontrolled', taking
      into account a change in their fractional exhaled nitric oxide level, increases
      133%.

PMID- 24581195
TI  - [Strategy to control methicillin-resistant Staphylococcus aureus: the 5 year
      experience of a hospital].
AB  - INTRODUCTION: Methicillin-resistant Staphylococcus aureus remains one of the
      principal resistant pathogens causing serious healthcareassociated infections.
      The objective of this study was to control and monitor methicillin-resistant
      Staphylococcus aureus cases using multimodal strategy in a Portuguese hospital.
      MATERIAL AND METHODS: Multistep procedure involving isolation measures and active
      surveillance cultures in a selected population (patients from other hospitals and
      nursing homes; history of hospitalization/ methicillin-resistant Staphylococcus
      aureus; intensive and intermediate care patients and, in other inpatient
      services, direct contacts of newly detected methicillin-resistant Staphylococcus
      aureus patients and, since 2012, patients doing hemodialysis). Other parallel
      activities: (a) review of isolation and standard precautions policy, (b)
      reinforcement of alcohol-based handrubs at point of patient care, (c) information
      sessions to health professionals, (d) targeted information flyer for health
      professionals, (e) information leaflet for patients/ visitors; (f) procedure
      monitoring by audit (g) patient decolonization in intensive and intermediate care
      units, with follow-up screenings. RESULTS: Between 2007 and 2012, methicillin
      resistant Staphylococcus aureus surveillance detected a decrease in proportion
      from 66% to 57% and, in density of incidence, from 1.80 to 0.68 cases per
      thousand days of hospitalization (p < 0.001; RR 0.38; CI95%: 0.29-0.49).
      DISCUSSION/CONCLUSION: According to published European data, using blood and
      cerebrospinal fluid isolates only, Portugal was the country with the highest
      level of methicillin-resistant Staphylococcus aureus in 2011. Using this
      inclusion criteria, our hospital reveled a proportion of methicillin-resistant
      Staphylococcus aureus below its national level (34% versus 55%) in 2011. Fighting
      methicillinresistant Staphylococcus aureus using a multimodal strategy is being
      effective in a high endemic level hospital, but perseverance is needed through
      continuous surveillance of cases, feed-back to professionals and procedure
      audits.

PMID- 24581196
TI  - [Total laparoscopic hysterectomy: retrospective analysis of 262 cases].
AB  - INTRODUCTION: Hysterectomy is one of the most common gynecological procedures and
      may be performed either by vaginal approach, laparotomy or laparoscopy. Although
      total laparoscopic hysterectomy has multiple advantages, conflicting major
      complication rates have been previously reported. OBJECTIVES: To describe our
      experience performing TLH and to evaluate complication rates. MATERIAL AND
      METHODS: A retrospective observational study of all total laparoscopic
      hysterectomy performed in our department, by the same surgical team, between
      April 2009 and March 2013 (n = 262), was conducted. Medical records were reviewed
      for patient characteristics, operating time, uterine weight, post-operative
      hemoglobin variation, length of hospital stay, and intra and postoperative
      complications. RESULTS: Patient average age was 48.9 +/- 9.0 years and 49.2% had
      previous abdominopelvic surgery. The average body mass index was 26.5 +/- 4.5
      kg/m(2) and 42% of women were either overweight or obese. The mean operating time
      during the total study period was 77.7 +/- 27.5 minutes, but it decreased
      significantly as the surgical team's training increased. Average uterine weight
      was 241.0 +/- 168.4 g and average hospital stay was 1.49 +/- 0.9 days. The mean
      postoperative hemoglobin variation was -1.5 +/- 0.8 g/dL. The major and minor
      complication rates were 1.5% (n = 4) and 11.5% (n = 30), respectively. One
      procedure was converted to laparotomy and two women had a vaginal vault
      dehiscence. No important urinary tract or bowel injuries occurred. CONCLUSIONS:
      This study demonstrates that, in experienced hands, total laparoscopic
      hysterectomy is safe and with low complications rates.

PMID- 24581197
TI  - [Factors predictive of retroperitoneal lymph node metastasis in endometrial
      cancer].
AB  - INTRODUCTION: It has been suggested that a complete staging may be safely omitted
      in endometrial carcinoma patients at low risk for lymph node metastasis. The
      purposes of our study were to explore the prognostic significance of pathologic
      factors for pelvic and paraaortic nodal spread and to validate the Mayo algorithm
      in order to identify patients in whom lymphadenectomy may be avoided. MATERIAL
      AND METHODS: We conducted a retrospective review including 208 patients,
      regarding the evaluation of pathologic variables and nodal metastases.
      Statistical analysis was performed using the chi-square test, the Fisher exact
      test and the Student's t-test. RESULTS: Myometrial invasion > 50% (p < 0.001),
      cervical invasion (p = 0.001), lymphovascular space invasion (p = 0.003) and
      positive peritoneal cytology (p = 0.03) were significant predictors of
      retroperitoneal lymph node dissemination. Pelvic lymph node metastases were
      predictive of positive paraaortic lymph nodes (p < 0.001). DISCUSSION: The Mayo
      algorithm identified patients without pelvic or paraaortic nodal metastases with
      a 98.4% negative predictive value (61/62). Myometral invasion <= 50% and absence
      of cervical and lymphovascular invasion presented a negative predictive value of
      98.8% (79/80). CONCLUSION: Although the Mayo criteria predict a very low
      likelihood of retroperitoneal nodal metastases, the combination of myometral
      invasion <= 50% and absence of cervical or lymphovascular invasion would have
      safely avoided lymphadenectomy in a larger number of women.

PMID- 24581198
TI  - Evaluation of functional recovery by motor functional independence measure test
      of elderly after hip fracture in Serbia.
AB  - INTRODUCTION: The aim of the study was to evaluate motor functional status
      measured by motor Functional Independence Measure (mFIM) test in population above
      65 years of age after the hip fracture. MATERIAL AND METHODS: We evaluated 203
      patients after hip fracture by mFIM test on 3 occasions: at admission (Period-1),
      at discharge (Period-2) and 3 months after discharge (Period-3); 3 age groups:
      Group(65-74), Group(75-84) and Group(85-up) and 2 groups concerning Severity
      Index (SI): group 0-1.99 (SI1) and group >= 2 (SI2). RESULTS: In same SI group
      there is significant increase in mFIM values for Period-2 and Period-3 for both
      genders and in first two age groups, while for those above 85 years of age with
      higher SI we found non-significant change in mFIM values between discharge and 3
      months post discharge period. DISCUSSION: The most significant improvement is
      obtained for women in first and third age groups and with higher SI. CONCLUSION:
      Gender is not significant predictor for motor functional recovery measured by
      mFIM test in patients with hip fracture, although the admittance mFIM is a good
      indicator for mFIM capacity recovery in women of certain age groups (first and
      third age groups).

PMID- 24581199
TI  - [SwapINN: analytic study about prescription swaps at pharmacies].
AB  - INTRODUCTION: In order to cut spending, compulsory INN prescription was suggested
      in Portugal during 2012. This instigated discussion among stakeholders in the
      matter. The authors studied prescription-dispensing dynamics in a real
      population. OBJECTIVES: To determine the percentage of swapped prescriptions; to
      assess factors associated with the swap; to analyse justifications for doing so;
      to quantify the cost difference for patients and the National Health Service.
      MATERIAL AND METHODS: Analytic study. Convenience sample consisting of all
      prescriptions from a Primary Health Care unit, from the 19th to the 23rd December
      2011. Third day follow-up, using phone call interviews. Software: Excel and SPSS.
      TESTS: Chi-square and Mann-Whitney, SL = 0.05. RESULTS: Total of 255
      prescriptions. Majority prescribed to women (62%), mean age of 52, four years of
      school education and for acute situations. A percentage of 31% of prescribed
      drugs were swapped. The swaps had no statistical relation with age, sex or
      literacy of the patient, nor with the prescriber or pharmacy. Swapping of
      prescribed drugs for chronic situations was lower (p < 0.001), as well as for
      original brand prescriptions (p < 0.001). Anti-infectious and anti-allergic were
      the most swapped groups (p = 0.009). Seventy-two percent of users were not aware
      of the swap. Regarding the swapped drugs, users paid on average 79% more than
      what was originally prescribed, and the National Health Service 5% more.
      DISCUSSION/CONCLUSION: The authors found changes in 31% of the prescriptions,
      with higher costs for both users and National Health Service. Selection,
      information and registration bias were considered. With compulsory INN
      prescriptions, we suggest regular analysis of prescription-dispensing dynamics,
      based on the available national data.

PMID- 24581200
TI  - [Promoting sustainable behavior change in body weight control].
AB  - There is a wide acknowledgement of obesity as a relevant clinical entity. Such
      relevance can be inferred by the huge worldwide amount of research and related
      health promotion and clinical efforts. Though the evidence sustains some cues for
      the therapeutic success, the overall long-term effectiveness of obesity treatment
      tends to be not so satisfactory. Scientific literature is not unequivocal in key
      areas of nutritional intervention, such as the magnitude of caloric restriction,
      proportion of macronutrients, meal frequency, among others. The same applies to
      the area of physical activity recommendation for weight control. As a correlate
      of this scenario of incertitude, there is a proliferation of interventions and
      there is a clear need to integrate the scientific and clinical evidence. This
      paper presents a narrative literature review of key issues of clinical practice
      in obesity, regarding a set of actions that, in the overall, have as main purpose
      the promotion of reduction and/or control of body weight. The role of the health
      professional is highlighted as a facilitator of acquisition of habits that favor
      weight control, by integrating the professional's scientific knowledge with the
      patient's readiness for and capacity to change. 

PMID- 24581201
TI  - Aerobic program in persons with stroke: a systematic review.
AB  - INTRODUCTION: The aim of this study was to perform a systematic review on the
      exercise trials post stroke. MATERIAL AND METHODS: Therefore, we conducted a
      systematic review of randomized controlled clinical trials published in PubMed
      and PEDro. The inclusion criteria were: Studies--randomized or controlled
      clinical trials; Participants--adults of any age with a clinical diagnosis of
      stroke; Interventions--any aerobic physical training aimed at improving
      cardiovascular capacity and/or function. Two independent reviewers categorized
      the selected trials, assessed methodological quality and extracted the relevant
      data. Various protocols were analyzed and used for both the assessment and
      physical training of post-stroke subjects. RESULTS: According to clinical trials
      analyze, a wide range of instruments were used to measure functional capacity.
      Ergospirometry and ergometry were found to be main devices in the assessment of
      cardiovascular capacity. Cycle ergometer training was the most commonly used
      training strategy, and conventional physiotherapy (based on stretching,
      strengthening, balance, coordination and gait training) was the most frequent
      control therapy. DISCUSSION: Training duration ranged from 4 weeks to 6 months;
      the mean weekly frequency was 3 sessions per week while training intensity ranged
      from 40 to 80% of maximal heart rate or VO2 peak. Duration of training sessions
      ranged from 25 minutes to 1 hour. CONCLUSION: Exercise training is a promising
      tool for the management of post-stroke patients, both in terms of improved
      cardiovascular and functional capacity. Further studies are needed to widen the
      scope of therapeutic management of this population.

PMID- 24581202
TI  - Integrated disease management: a critical review of foreign and Portuguese
      experience.
AB  - INTRODUCTION: The present article reviews findings from empirical evaluations of
      integrated disease management programmes. The objective is to provide insights on
      integration levels, priority interventions and their effect on patient outcomes.
      MATERIAL AND METHODS: The literature review identified 1 251 articles, published
      from 2006 to 2011. Upon a detailed screening 61 articles were selected for
      bibliometric analysis and critical discussion. RESULTS: Among several findings,
      it can be noted that United States of America is the country with the highest
      amount of published evidence on the subject under study. The most frequently
      referred disease is diabetes mellitus and the main reported issue of integrated
      disease management is self-management support. The majority of the studies were
      developed and exclusively managed by managed care organizations, organized family
      doctors or hospitals. From a total of 360 interventions reported in studies,
      patient interventions are the most frequently used across all disease groups,
      followed by professional interventions. To monitor the effectiveness of the
      disease programmes, the most frequently used outcomes are patient physiological
      measures, service use and patient health status. DISCUSSION: Every country has
      its own way to implement the integrated disease management strategy. The focus of
      practice lies on patient empowerment, particularly through self-management.
      Physiological measures and service use are the outcomes with the highest rate of
      assessment, which are also the indicators that show higher impact among all
      integrated disease management programmes. CONCLUSION: The Portuguese health care
      system still faces challenges in the coordination and integration of care for
      patients with chronic disease thus improvements at integrated disease management
      programmes should be incorporate.

PMID- 24581203
TI  - [The disclosed DSM-5: what impact will it have on forensic psychiatry?].
AB  - INTRODUCTION: On 10 February 2010, the American Psychiatric Association published
      an online draft of the fifth edition of the Diagnostic and Statistical Manual of
      Mental Disorders, which, like the previous editions, after having received
      several comments and contributions, was subject during the next following years,
      to the technical and scientific scrutiny, and, of course, susceptible to
      modification leading to a final improved version. MATERIAL AND METHODS: This
      article aims to analyze the changes proposed by this new review, investigate
      whether these have implications in the field of Forensic Psychiatry and discuss
      the implications identified. DISCUSSION: In this perspective, the object of
      analysis are issues related to the classification and structuring of nosological
      entities, with special focus on personality disorders, substance abuse disorders,
      sexual and gender identity disorders, anxiety disorders, dissociative disorders,
      psychotic disorders and also disorders suggested by external sources. CONCLUSION:
      the main changes proposed are essentially about diagnostic criteria, which, for
      some of nosological entities, may hinder the outcome of the expert assessment,
      while for others there could be otherwise, since the introduction of new models
      closer to reality appears to offer greater objectivity and diagnostic rigor.

PMID- 24581204
TI  - [Twin pregnancy with a complete hydatiform mole and a viable co-twin].
AB  - A complete hydatiform mole coexisting with a live, viable twin is a rare event.
      The diagnosis is challenging, and is normally achieved only at second trimester.
      It may be associated with thyrotoxicosis, vaginal bleeding, preeclampsia, fetal
      death or persistent throphoblastic disease. The authors describe the case of a
      pregnant woman presenting with first trimester bleeding. Ultrasound revealed a
      twin pregnancy with a viable twin and another placenta apparently detached. At 16
      gestational weeks ultrasound revealed a live fetus with a normal placenta and a
      separate vacuolated and vascularized mass. Facing the hypothesis of gestational
      trophoblastic disease, the couple chose pregnancy interruption. Given the rarity
      of this situation, a high index of suspicion is needed to achieve the diagnosis.
      Despite the existence of case reports with good fetal and maternal outcome, the
      decision of pregnancy continuation should be made by the informed parents. 

PMID- 24581205
TI  - Arachnoid cyst spontaneous rupture.
AB  - Arachnoid cysts are benign congenital cerebrospinal fluid collections, usually
      asymptomatic and diagnosed incidentally in children or adolescents. They may
      become symptomatic after enlargement or complications, frequently presenting with
      symptoms of intracranial hypertension. We report an unusual case of progressive
      refractory headache in an adult patient due to an arachnoid cyst spontaneous
      rupture. Although clinical improvement occurred with conservative treatment, the
      subdural hygroma progressively enlarged and surgical treatment was ultimately
      needed. Spontaneous rupture is a very rare complication of arachnoid cysts.
      Accumulation of cerebrospinal fluid accumulation in the subdural space causes
      sustained intracranial hypertension that may be life-threatening and frequently
      requires surgical treatment. Patients with arachnoid cysts must be informed on
      their small vulnerability to cyst rupture and be aware that a sudden and severe
      headache, especially if starting after minor trauma or a Valsalva manoeuvre,
      always requires medical evaluation. 

PMID- 24581206
TI  - [Hospital protocol for snakebite victims management].
AB  - Venomous snakebites are relatively rare in Portugal. Pediatric victims present
      with greater severity and are at risk of fatal complications. Clinical management
      protocols are the gold standard of care worldwide. We report two cases of
      venomous adder bites in pediatric patients. Based on a literature review we also
      discuss the clinical management and present a treatment protocol that ensures
      multidisciplinary and updated practice by medical teams. 

PMID- 24581207
TI  - [This gentleman was Joao Semana].

PMID- 24581208
TI  - Scrotal edema in dilated cardiomyopathy.

PMID- 24581209
TI  - Cavitary lung lesions.

PMID- 24581210
TI  - Miniscrew implant applications in contemporary orthodontics.
AB  - The need for orthodontic treatment modalities that provide maximal anchorage
      control but with minimal patient compliance requirements has led to the
      development of implant-assisted orthodontics and dentofacial orthopedics.
      Skeletal anchorage with miniscrew implants has no patient compliance requirements
      and has been widely incorporated in orthodontic practice. Miniscrew implants are
      now routinely used as anchorage devices in orthodontic treatment. This review
      summarizes recent data regarding the interpretation of bone data (i.e., bone
      quantity and quality) obtained by preoperative diagnostic computed tomography
      (CT) or by cone-beam computed tomography (CBCT) prior to miniscrew implant
      placement. Such data are essential when selecting appropriate sites for miniscrew
      implant placement. Bone characteristics that are indications and
      contraindications for treatment with miniscrew implants are discussed.
      Additionally, bicortical orthodontic skeletal anchorage, risks associated with
      miniscrew implant failure, and miniscrew implants for nonsurgical correction of
      occlusal cant or vertical excess are reviewed. Finally, implant stability is
      compared between titanium alloy and stainless steel miniscrew implants.

PMID- 24581211
TI  - Eugenosedin-A ameliorates hyperlipidemia-induced vascular endothelial dysfunction
      via inhibition of alpha1-adrenoceptor/5-HT activity and NADPH oxidase expression.
AB  - Eugenosedin-A (Eu-A) effects on vascular endothelial dysfunction and oxidative
      stress in a hyperlipidemic rat model were investigated. Rats were randomly
      divided into four groups: two control groups and two treatment groups. The
      control rats received a regular diet or high fat diet (HFD); the treatment rats
      fed received an HFD with 5 mg/kg Eu-A or atorvastatin for 10 weeks. No changes in
      serotonin levels were observed in the four groups; norepinephrine levels were
      enhanced in the HFD group which was attenuated by Eu-A and atorvastatin. In the
      HFD group, the vascular reactivity was increased by vasoconstrictors (5
      nonyloxytryptamine, 5-HT, and phenylephrine) and decreased by an endothelium
      dependent vasorelaxant, carbachol. Protein levels of alpha1-adrenergic receptors
      (not 5-HT1B/2A), reactive oxygen species (ROS) p47(phox), p67(phox), and
      gp91(phox), and oxidative damage markers 3-nitrotyrosine (3-NT) and 4-hydroxy-2
      nonenal (4-HNE) were increased, but endothelial nitric oxide synthase (eNOS), P
      eNOS and vasodilator-stimulated phosphoprotein phosphorylation (P-VASP) were
      decreased. Catalase and superoxide dismutase (SOD-1 and SOD-2) proteins were
      increased, but glutathione peroxidase (GPx) was decreased in the aorta. Eu-A and
      atorvastatin reduced vasoconstrictor-induced aortic contractions that might be
      related to 5-HT1B/2A and alpha1-adrenergic receptors inhibitory activities. Eu-A
      and atorvastatin improved eNOS/P-eNOS, P-VASP, GPx, and malondialdehyde (MDA)
      levels, and decreased ROS and oxidative damage markers. Taken together, we
      suggest that Eu-A can ameliorate hyperlipidemia-induced vascular endothelial
      dysfunction and oxidative dysregulation.

PMID- 24581212
TI  - Functional connectivity between parietal cortex and the cardiac autonomic system
      in uremics.
AB  - Although the central autonomic network (CAN) has been well researched in animal
      models, the CAN in humans is still unclear, especially for cardiovascular
      control. This study aimed to investigate which areas of the cerebral cortices are
      associated with the peripheral cardiac autonomic control involved in the CAN in
      uremic patients with autonomic dysfunction and normal controls. The central and
      peripheral autonomic network in 19 uremic patients with significant autonomic
      dysfunction and 24 age- and sex-matched controls [mean age +/- standard deviation
      (SD), 55.16 +/- 10.45 years and 55.42 +/- 5.42 years, respectively] were
      evaluated by simultaneous spectral analysis of electroencephalography (EEG) and
      electrocardiography recording (ECG), along with serial autonomic tests [autonomic
      questionnaire and orthostatic blood pressure (BP) change]. Only frequency-domain
      heart rate variability (f-HRV) during the deep-breathing stage could
      differentiate the two groups. Although there is no significant difference in f
      HRV during the quiet-breathing stage, different patterns of central oscillation
      and their correlation with peripheral cardiac autonomic indices could be found
      for the two groups. Although the power of specific EEG bands under electrode T3
      and T6 correlated significantly with the power of peripheral HRV indices in the
      control group, those under electrodes P3 and Pz had significant correlations in
      the uremic group suggesting a role of functional connectivity between them. In
      addition, sympathetic activity is correlated with slow wave EEG (theta/delta)
      power whereas parasympathetic activity is correlated with fast wave EEG (beta)
      power. In conclusion, there is functional connectivity between the parietal
      cortex and the peripheral cardiac autonomic system (PAN) in uremics and the
      pattern of central autonomic connectivity differs between uremic patients with
      autonomic dysfunction and normal controls.

PMID- 24581213
TI  - Association between auditory P300, psychopathology, and memory function in drug
      naive schizophrenia.
AB  - The aim of this study was to explore memory deficits and psychopathology and
      their relationships with P300 in drug-naive patients with schizophrenia. The
      Positive and Negative Syndrome Scale (PANSS) and the Wechsler Memory Scale
      Revised were administered. Auditory event-related potentials elicited by an
      oddball paradigm were obtained. After controlling for age, sex, the results
      showed a statistically significant negative correlation between the total PANSS
      score and P300 amplitude at the parietal position (r = -0.66, p < 0.05).
      Moreover, visual memory was significantly positively correlated with P300
      amplitude at the parietal position (r = 0.67, p < 0.05). After controlling for
      the duration of illness, the above correlations remained statistically
      significant. The correlation between P300 and the severity of psychopathology was
      reconfirmed in drug-naive patients with schizophrenia. A possible contribution of
      memory decompensation in P300 among drug-naive patients with schizophrenia may be
      considered, and the compensatory or Default Model Network might be a possible
      explanation of this association.

PMID- 24581214
TI  - Different sling procedures for stress urinary incontinence: a lesson from 453
      patients.
AB  - Several midurethral sling (MUS) procedures, such as tension-free vaginal tape
      (TVT), TVT obturator (TVT-O), tension-free vaginal tape SECUR (TVT-S), and
      pubovaginal sling (PVS), have been used for the treatment of female stress
      urinary incontinence (SUI); however, which method is best for a particular
      patient group is not known. This study aimed to identify the best rationale for
      choosing the optimal MUS procedure for each patient. In total, 453 consecutive
      female patients with SUI who were treated with MUSs in West China Hospital of
      Sichuan University from September 2003 to September 2011 were enrolled in this
      study. All the patients underwent comprehensive pre-, intra-, and postoperative
      evaluations, including collection of demographic information, pelvic examination,
      and urodynamic testing, and operation-related complications were recorded. The
      Incontinence Quality of Life questionnaire was also completed. Under local or
      general anesthesia, 105 cases were treated with TVT, 243 with TVT-O, 90 with TVT
      S, and 15 with PVS. Patients with different profiles in terms of age, symptom
      duration, concomitant procedures, urodynamic parameters, and pelvic organ
      prolapse (POP) quantification score were treated successfully; the body mass
      index did not differ significantly among the various treatment options. The cure
      and improvement rates were similar among the treatment groups: 97.14% (102/105)
      in TVT, 100% (243/243) in TVT-O, 98.89% (89/90) in TVT-S, and 100% (15/15) in
      PVS. Only minor complications were experienced by the patients. In conclusion,
      each MUS procedure was observed to be safe and effective in different
      subpopulations of patients, and the results suggest that appropriate patient
      selection is crucial for the success of each MUS procedure. 

PMID- 24581215
TI  - Liver function tests may be useful tools for advanced cancer patient care: a
      preliminary single-center result.
AB  - Accurate prognostication in advanced cancer may facilitate better palliative
      care. An objective marker may be more applicable and appropriate than a
      subjective evaluation by physicians. The aim of this study was to evaluate liver
      function tests as useful prognostic factors for survival in patients with
      advanced cancer. We recruited advanced cancer patients from January 2007 to
      December 2009. Data on age, sex, cancer diagnosis, site of metastases, clinical
      symptoms, and performance status were collected at the time of admission to the
      palliative care unit. Analyzed laboratory data were obtained on the Day 1 of
      admission to the palliative care unit. A total of 522 patients were enrolled; 322
      (61.7%) of them were males. The mean age was 60.6 +/- 13.2 years. Multiple
      logistic regression analysis adjusting for age and sex demonstrated aspartate
      transaminase (AST) > 80 IU/L [odds ratio (OR) = 2.01, p = 0.010] and alanine
      transaminase > 80 IU/L (OR = 1.89, p = 0.047) were independently significant
      prognostic factors of death within 14 days. AST > 80 IU/L (OR = 3.67, p = 0.017)
      and albumin < 3.0 g/dL (OR = 1.98, p = 0.048) were independently significant
      prognostic factors of death within 6 months. Liver function tests may be useful
      prognostic factors for patients in the palliative care unit, in addition to being
      useful for patients with hepatobiliary cancer or liver metastasis. These
      biochemical tests of liver function with cutoff values can easily be used in
      palliative care.

PMID- 24581216
TI  - Comparison of Ho:YAG laser and pneumatic lithotripsy in the treatment of impacted
      ureteral stones: an analysis of risk factors.
AB  - The aim was to compare pneumatic and holmium:yttrium-aluminum-garnet laser in the
      treatment of impacted ureteral stones with different locations and to identify
      the risk factors for complications. Between March 2005 and November 2012, a total
      of 230 patients underwent ureteroscopic lithotripsy for impacted stones. Of the
      patients, 117 had pneumatic and 113 had laser lithotripsy for the fragmentation
      of the stones. Treatment outcomes based on evidence of being stone free were
      evaluated. Preoperative, operative, and postoperative follow-up findings were
      analyzed and compared. There was a difference between the two groups according to
      overall stone clearance rate (93.8% vs. 80.3%, p = 0.002). There was no
      statistically significant difference for distal location between the laser and
      pneumatic groups (96.8% vs. 91.7%, p =0.288). For 10 patients with intrarenally
      migrated stones who were managed with flexible ureterorenoscopy in the same
      session, laser lithotripsy was more successful than pneumatic for proximal
      ureteral stone (94.4% vs. 67.9%, p = 0.007). The overall complication rate was
      26.1%. There was no statistically significant difference between the two groups
      (29% vs. 23%, p = 0.296). Multivariate logistic regression analysis revealed that
      the proximal location was a statistically significant parameter for the
      occurrence of complications in both groups (p = 0.001 for PL, p = 0.004 for
      laser). The pneumatic and holmium:yttrium-aluminum-garnet laser lithotripsy are
      effective in the treatment of distal impacted stones. Both treatments with
      semirigid ureteroscopy are acceptable for proximal impacted ureteral stones, but
      holmium laser lithotripsy has an advantage of use with flexible ureteroscope for
      intrarenally migrated stone.

PMID- 24581217
TI  - Ovarian malignant Brenner tumor in patients over 65 years of age.

PMID- 24581218
TI  - Fulminant type 1 diabetes during pregnancy in Chinese patients.

PMID- 24581219
TI  - Successful management of a massive bone defect of the distal femur and limb
      shortening in two stages.

PMID- 24581220
TI  - Par6 is an essential mediator of apoptotic response to transforming growth factor
      beta in NMuMG immortalized mammary cells.
AB  - BACKGROUND: We previously observed that the TGFbeta-Par6 pathway mediates loss of
      polarity and apoptosis in NMuMG cells. Here we investigate the contribution of
      Par6 versus TGFbeta receptor I activation to TGFbeta-induced apoptosis in
      association with changes in apico-basal polarity. We focus on the effect of Par6
      activation on alpha6beta4 integrin expression and localization, and Nuclear
      Factor-kappaB (p65/RelA) activation, previously shown to mediate polarity
      dependent cell survival. METHODS: Using immunoblotting and/or immunofluorescence
      we investigated the effect of TGFbeta1 on apoptosis, alpha6, beta4 and beta1
      integrin expression/localization, and p65/RelA phosphorylation/localization in
      monolayer and three-dimensional (3D) cultures of NMuMG cells with an overactive
      or inactive Par6 pathway. Results were quantified by band densitometry or as
      percent of 3D structures displaying a phenotype. Differences among means were
      compared by two-way ANOVA. RESULTS: Blocking Par6 activation inhibits TGFbeta
      induced apoptosis. Par6 overactivation enhances TGFbeta-induced apoptosis,
      notably after 6-day exposure to TGFbeta (p < 0.001), a time when parental NMuMG
      cells no longer respond to TGFbeta apoptotic stimuli. 48-hour TGFbeta treatment
      reduced beta4 integrin levels in NMuMG monolayers and significantly reduced the
      basal localization of alpha6 (p < 0.001) and beta4 (p < 0.001) integrin in NMuMG
      3D structures, which was dependent on both Par6 and TGFbeta receptor I activation
      and paralleled apoptotic response. After 6-day exposure to TGFbeta, Par6
      dependent changes to beta4 integrin were no longer apparent, but there was
      reduced phosphorylation of p65/RelA (p < 0.001) only in Par6 overexpressing
      cells. Differences in p65/RelA localization were not observed among the different
      cell lines after 48-hour TGFbeta exposure. CONCLUSIONS: Par6 and TGFbeta receptor
      I activation are both necessary for TGFbeta-induced apoptosis in NMuMG cells.
      Importantly, Par6 overexpression enhances the sensitivity of NMuMG to TGFbeta
      induced apoptosis, notably upon prolonged exposure to this growth factor, when
      NMuMG parental cells are usually apoptosis-resistant. Thus, endogenous Par6 level
      might be important in determining whether TGFbeta will function as either a pro
      apoptotic or pro-survival factor in breast cancer, and potentially aid in
      predicting patient's prognosis and therapy response.

PMID- 24581221
TI  - Deregulation of subcellular biometal homeostasis through loss of the metal
      transporter, Zip7, in a childhood neurodegenerative disorder.
AB  - BACKGROUND: Aberrant biometal metabolism is a key feature of neurodegenerative
      disorders including Alzheimer's and Parkinson's diseases. Metal modulating
      compounds are promising therapeutics for neurodegeneration, but their mechanism
      of action remains poorly understood. Neuronal ceroid lipofuscinoses (NCLs),
      caused by mutations in CLN genes, are fatal childhood neurodegenerative lysosomal
      storage diseases without a cure. We previously showed biometal accumulation in
      ovine and murine models of the CLN6 variant NCL, but the mechanism is unknown.
      This study extended the concept that alteration of biometal functions is involved
      in pathology in these disorders, and investigated molecular mechanisms underlying
      impaired biometal trafficking in CLN6 disease. RESULTS: We observed significant
      region-specific biometal accumulation and deregulation of metal trafficking
      pathways prior to disease onset in CLN6 affected sheep. Substantial progressive
      loss of the ER/Golgi-resident Zn transporter, Zip7, which colocalized with the
      disease-associated protein, CLN6, may contribute to the subcellular deregulation
      of biometal homeostasis in NCLs. Importantly, the metal-complex, ZnII(atsm),
      induced Zip7 upregulation, promoted Zn redistribution and restored Zn-dependent
      functions in primary mouse Cln6 deficient neurons and astrocytes. CONCLUSIONS:
      This study demonstrates the central role of the metal transporter, Zip7, in the
      aberrant biometal metabolism of CLN6 variants of NCL and further highlights the
      key contribution of deregulated biometal trafficking to the pathology of
      neurodegenerative diseases. Importantly, our results suggest that ZnII(atsm) may
      be a candidate for therapeutic trials for NCLs.

PMID- 24581222
TI  - Gene expression profiling of Epstein-Barr virus-positive diffuse large B-cell
      lymphoma of the elderly reveals alterations of characteristic oncogenetic
      pathways.
AB  - Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (DLBCL) of the
      elderly (EBV[+]DLBCL-E) is classified as a subtype of DLBCL. Until now, its
      molecular pathogenesis has remained unknown. To identify pathways characteristic
      of EBV(+)DLBCL-E, gene expression profiling of five EBV(+)DLBCL-E and seven EBV
      negative DLBCL (EBV[-]DLBCL) cases was undertaken using human oligonucleotide
      microarray analysis. Gene set enrichment analysis and gene ontology analysis
      showed that gene sets of the Janus kinase-signal transducer and activator of
      transcription (JAK-STAT) and nuclear factor kappa B (NF-kappaB) pathways were
      enriched in EBV(+)DLBCL-E cases. To confirm the results of the expression
      profiles, in vitro analysis was performed. Expression profiling analysis showed
      that high activation of the JAK-STAT and NF-kappaB pathways was induced by EBV
      infection into DLBCL cell lines. Activation of the NF-kappaB pathway was
      confirmed in EBV-infected cell lines using an electrophoretic mobility shift
      assay. Western blot analysis revealed an increased protein expression level of
      phosphorylated signal transducer and activator of transcription 3 (STAT3) in an
      EBV-infected cell line. Protein expression of phosphorylated STAT3 was frequently
      observed in lymphoma cells of EBV(+)DLBCL-E clinical samples using
      immunohistochemistry (EBV[+]DLBCL-E: 80.0% [n = 20/25] versus EBV[-]DLBCL: 38.9%
      [n = 14/36]; P = 0.001). The results of the present study suggest that activation
      of the JAK-STAT and NF-kappaB pathways was characteristic of EBV(+)DLBCL-E, which
      may reflect the nature of EBV-positive tumor cells. Targeting these pathways as
      therapies might improve clinical outcomes of EBV(+)DLBCL-E.

PMID- 24581223
TI  - Altered miRNA expression in canine retinas during normal development and in
      models of retinal degeneration.
AB  - BACKGROUND: Although more than 246 loci/genes are associated with inherited
      retinal diseases, the mechanistic events that link genetic mutations to
      photoreceptor cell death are poorly understood. miRNAs play a relevant role
      during retinal development and disease. Thus, as a first step in characterizing
      miRNA involvement during disease expression and progression, we examined miRNAs
      expression changes in normal retinal development and in four canine models of
      retinal degenerative disease. RESULTS: The initial microarray analysis showed
      that 50 miRNAs were differentially expressed (DE) early (3 vs. 7 wks) in normal
      retina development, while only 2 were DE between 7 and 16 wks, when the dog
      retina is fully mature. miRNA expression profiles were similar between dogs
      affected with xlpra2, an early-onset retinal disease caused by a microdeletion in
      RPGRORF15, and normal dogs early in development (3 wks) and at the peak of
      photoreceptor death (7 wks), when only 2 miRNAs were DE. However, the expression
      varied much more markedly during the chronic cell death stage at 16 wks (118 up
      /55 down-regulated miRNAs). Functional analyses indicated that these DE miRNAs
      are associated with an increased inflammatory response, as well as cell
      death/survival. qRT-PCR of selected apoptosis-related miRNAs ("apoptomirs")
      confirmed the microarray results in xlpra2, and extended the analysis to the
      early-onset retinal diseases rcd1 (PDE6B-mutation) and erd (STK38L-mutation), as
      well as the slowly progressing prcd (PRCD-mutation). The results showed up
      regulation of anti-apoptotic (miR-9, -19a, -20, -21, -29b, -146a, -155, -221) and
      down-regulation of pro-apoptotic (miR-122, -129) apoptomirs in the early-onset
      diseases and, with few exceptions, also in the prcd-mutants. CONCLUSIONS: Our
      results suggest that apoptomirs might be expressed by diseased retinas in an
      attempt to counteract the degenerative process. The pattern of expression in
      diseased retinas mirrored the morphology and cell death kinetics previously
      described for these diseases. This study suggests that common miRNA regulatory
      mechanisms may be involved in retinal degeneration processes and provides
      attractive opportunities for the development of novel miRNA-based therapies to
      delay the progression of the degenerative process.

PMID- 24581225
TI  - Identification, occurrence, and validation of DRE and ABRE Cis-regulatory motifs
      in the promoter regions of genes of Arabidopsis thaliana.
AB  - Plants posses a complex co-regulatory network which helps them to elicit a
      response under diverse adverse conditions. We used an in silico approach to
      identify the genes with both DRE and ABRE motifs in their promoter regions in
      Arabidopsis thaliana. Our results showed that Arabidopsis contains a set of 2,052
      genes with ABRE and DRE motifs in their promoter regions. Approximately 72% or
      more of the total predicted 2,052 genes had a gap distance of less than 400 bp
      between DRE and ABRE motifs. For positional orientation of the DRE and ABRE
      motifs, we found that the DR form (one in direct and the other one in reverse
      orientation) was more prevalent than other forms. These predicted 2,052 genes
      include 155 transcription factors. Using microarray data from The Arabidopsis
      Information Resource (TAIR) database, we present 44 transcription factors out of
      155 which are upregulated by more than twofold in response to osmotic stress and
      ABA treatment. Fifty-one transcripts from the one predicted above were validated
      using semiquantitative expression analysis to support the microarray data in
      TAIR. Taken together, we report a set of genes containing both DRE and ABRE
      motifs in their promoter regions in A. thaliana, which can be useful to
      understand the role of ABA under osmotic stress condition. 

PMID- 24581224
TI  - Possible molecular mechanisms linking air pollution and asthma in children.
AB  - BACKGROUND: Air pollution has many effects on the health of both adults and
      children, but children's vulnerability is unique. The aim of this review is to
      discuss the possible molecular mechanisms linking air pollution and asthma in
      children, also taking into account their genetic and epigenetic characteristics.
      RESULTS: Air pollutants appear able to induce airway inflammation and increase
      asthma morbidity in children. A better definition of mechanisms related to
      pollution-induced airway inflammation in asthmatic children is needed in order to
      find new clinical and therapeutic strategies for preventing the exacerbation of
      asthma. Moreover, reducing pollution-induced oxidative stress and consequent lung
      injury could decrease children's susceptibility to air pollution. This would be
      extremely useful not only for the asthmatic children who seem to have a genetic
      susceptibility to oxidative stress, but also for the healthy population. In
      addition, epigenetics seems to have a role in the lung damage induced by air
      pollution. Finally, a number of epidemiological studies have demonstrated that
      exposure to common air pollutants plays a role in the susceptibility to, and
      severity of respiratory infections. CONCLUSIONS: Air pollution has many negative
      effects on pediatric health and it is recognised as a serious health hazard.
      There seems to be an association of air pollution with an increased risk of
      asthma exacerbations and acute respiratory infections. However, further studies
      are needed in order to clarify the specific mechanism of action of different air
      pollutants, identify genetic polymorphisms that modify airway responses to
      pollution, and investigate the effectiveness of new preventive and/or therapeutic
      approaches for subjects with low antioxidant enzyme levels. Moreover, as that
      epigenetic changes are inheritable during cell division and may be transmitted to
      subsequent generations, it is very important to clarify the role of epigenetics
      in the relationship between air pollution and lung disease in asthmatic and
      healthy children.

PMID- 24581227
TI  - Assessment of asymmetric leg loading before and after total hip arthroplasty
      using instrumented shoes.
AB  - BACKGROUND: Total hip arthroplasty is a successful surgical treatment in patients
      with osteoarthritis of the hip. Different questionnaires are used by the
      clinicians to assess functional capacity and the patient's pain, despite these
      questionnaires are known to be subjective. Furthermore, many studies agree that
      kinematic and kinetic parameters are crucial to evaluate and to provide useful
      information about the patient's evolution for clinicians and rehabilitation
      specialists. However, these quantities can currently only be obtained in a fully
      equipped gait laboratory. Instrumented shoes can quantify gait velocity, kinetic,
      kinematic and symmetry parameters. The aim of this study was to investigate
      whether the instrumented shoes is a sufficiently sensitive instrument to show
      differences in mobility performance before and after total hip arthroplasty.
      METHODS: In this study, patients undergoing total hip arthroplasty were measured
      before and 6-8 months after total hip arthroplasty. Both measurement sessions
      include 2 functional mobility tasks while the subject was wearing instrumented
      shoes. Before each measurement the Harris Hip Score and the Traditional Western
      Ontario and McMaster Universities osteoarthritis index were administered as well.
      RESULTS: The stance time and the average vertical ground reaction force measured
      with the instrumented shoes during walking, and their symmetry index, showed
      significant differences before and after total hip arthroplasty. However, the
      data obtained with the sit to stand test did not reveal this improvement after
      surgery. CONCLUSIONS: Our results show that inter-limb asymmetry during a walking
      activity can be evaluated with the instrumented shoes before and after total hip
      arthroplasty in an outpatient clinical setting.

PMID- 24581229
TI  - The perceptions of professional soccer players on the risk of injury from
      competition and training on natural grass and 3rd generation artificial turf.
AB  - BACKGROUND: The purpose of this study was to describe professional soccer
      players' perceptions towards injuries, physical recovery and the effect of
      surface related factors on injury resulting from soccer participation on 3rd
      generation artificial turf (FT) compared to natural grass (NG). METHODS:
      Information was collected through a questionnaire that was completed by 99
      professional soccer players from 6 teams competing in Major League Soccer (MLS)
      during the 2011 season. RESULTS: The majority (93% and 95%) of the players
      reported that playing surface type and quality influenced the risk of sustaining
      an injury. Players believed that playing and training on FT increased the risk of
      sustaining a non-contact injury as opposed to a contact injury. The players
      identified three surface related risk factors on FT, which they related to
      injuries and greater recovery times: 1) Greater surface stiffness 2) Greater
      surface friction 3) Larger metabolic cost to playing on artificial grounds.
      Overall, 94% of the players chose FT as the surface most likely to increase the
      risk of sustaining an injury. CONCLUSIONS: Players believe that the risk of
      injury differs according to surface type, and that FT is associated with an
      increased risk of non-contact injury. Future studies should be designed
      prospectively to systematically track the perceptions of groups of professional
      players training and competing on FT and NG.

PMID- 24581228
TI  - Surgical ward rounds in England: a trainee-led multi-centre study of current
      practice.
AB  - BACKGROUND: Recent guidance advocates daily consultant-led ward rounds, conducted
      in the morning with the presence of senior nursing staff and minimising patients
      on outlying wards. These recommendations aim to improve patient management
      through timely investigations, treatment and discharge. This study sought to
      evaluate the current surgical ward round practices in England. METHODS:
      Information regarding timing and staffing levels of surgical ward rounds was
      collected prospectively over a one-week period. The location of each patient was
      also documented. Two surgical trainee research collaboratives coordinated data
      collection from 19 hospitals and 13 surgical subspecialties. RESULTS: Data from
      471 ward rounds involving 5622 patient encounters was obtained. 367 (77.9%) ward
      rounds commenced before 9am. Of 422 weekday rounds, 190 (45%) were consultant-led
      compared with 33 of the 49 (67%) weekend rounds. 2474 (44%) patients were seen
      with a nurse present. 1518 patients (27%) were classified as outliers, with 361
      ward rounds (67%) reporting at least one outlying patient. CONCLUSION:
      Recommendations for daily consultant-led multi disciplinary ward rounds are
      poorly implemented in surgical practice, and patients continue to be managed on
      outlying wards. Although strategies may be employed to improve nursing attendance
      on ward rounds, substantial changes to workforce planning would be required to
      deliver daily consultant-led care. An increasing political focus on patient
      outcomes at weekends may prompt changes in these areas.

PMID- 24581230
TI  - Validation of the effects of TGF-beta1 on tumor recurrence and prognosis through
      tumor retrieval and cell mechanical properties.
AB  - BACKGROUND: In vivo, the transforming growth factor-beta1 (TGF-beta1)-induced
      epithelial to mesenchymal transition (EMT) occurs in seconds during cancer cells
      intravasation and extravasation. Although it has been established that cellular
      stiffness can change as a cancer cell transformed, the precise relationship
      between TGF-beta1-induced mesenchymal stem cell mechanics and cancer prognosis
      remains unclear. Accordingly, it is hard to define the effects of EMT on cell
      mechanical properties (CMs), tumor recurrence and metastasis risks. This study
      bridges physical and pathological disciplines to reconcile single-cell mechanical
      measurements of tumor cells. METHODS AND RESULTS: We developed a microplate
      measurement system (MMS) and revealed the intrinsic divergent tumor composition
      of retrieval cells by cell stiffness and adhesion force and flow cytometry
      analysis. After flow cytometry sorting, we could measure the differences in CMs
      of the Sca-1+-CD44+ (mesenchymal-stem-cell-type) and the other subgroups. As well
      as the stiffer and heterogeneous compositions among tumor tissues with higher
      recurrence risk were depicted by MMS and atomic force microscopy (AFM). An in
      vitro experiment validated that Lewis lung carcinoma (LLC) cells acquired higher
      CMs and motility after EMT, but abrogated by SB-505124 inhibition. Concomitantly,
      the CD31, MMP13 and TGF-beta1 enriched micro-environment in the tumor was
      associated with higher recurrence and distal lung metastasis risks. Furthermore,
      we report a comprehensive effort to correlate CMs to tumor-prognosis indicators,
      in which a decreased body weight gain ratio (BWG) and increased tumor weight (TW)
      were correlated with increased CMs. CONCLUSIONS: Together, we determined that TGF
      beta1 was significantly associated with malignant tumor progressing. In terms of
      clinical applications, local tumor excision followed by MMS analysis offers an
      opportunity to predict tumor recurrence and metastasis risks.

PMID- 24581231
TI  - Akt inhibitor MK-2206 promotes anti-tumor activity and cell death by modulation
      of AIF and Ezrin in colorectal cancer.
AB  - BACKGROUND: There is extensive evidence for the role of aberrant cell survival
      signaling mechanisms in cancer progression and metastasis. Akt is a major
      component of cell survival-signaling mechanisms in several types of cancer. It
      has been shown that activated Akt stabilizes XIAP by S87 phosphorylation leading
      to survivin/XIAP complex formation, caspase inhibition and cytoprotection of
      cancer cells. We have reported that TGFbeta/PKA/PP2A-mediated tumor suppressor
      signaling regulates Akt phosphorylation in association with the dissociation of
      survivin/XIAP complexes leading to inhibition of stress-dependent induction of
      cell survival. METHODS: IGF1R-dependent colon cancer cells (GEO and CBS) were
      used for the study. Effects on cell proliferation and cell death were determined
      in the presence of MK-2206. Xenograft studies were performed to determine the
      effect of MK-2206 on tumor volume. The effect on various cell death markers such
      as XIAP, survivin, AIF, Ezrin, pEzrin was determined by western blot analysis.
      Graph pad 5.0 was used for statistical analysis. P < 0.05 was considered
      significant. RESULTS: We characterized the mechanisms by which a novel Akt kinase
      inhibitor MK-2206 induced cell death in IGF1R-dependent colorectal cancer (CRC)
      cells with upregulated PI3K/Akt signaling in response to IGF1R activation. MK
      2206 treatment generated a significant reduction in tumor growth in vivo and
      promoted cell death through two mechanisms. This is the first report
      demonstrating that Akt inactivation by MK-2206 leads to induction of and
      mitochondria-to-nuclear localization of the Apoptosis Inducing Factor (AIF),
      which is involved in caspase-independent cell death. We also observed that
      exposure to MK-2206 dephosphorylated Ezrin at the T567 site leading to the
      disruption of Akt-pEzrin-XIAP cell survival signaling. Ezrin phosphorylation at
      this site has been associated with malignant progression in solid tumors.
      CONCLUSION: The identification of these 2 novel mechanisms leading to induction
      of cell death indicates MK-2206 might be a potential clinical candidate for
      therapeutic targeting of the subset of IGF1R-dependent cancers in CRC.

PMID- 24581233
TI  - Exploring the impact of staff absenteeism on patient satisfaction using routine
      databases in a university hospital.
AB  - AIM: To explore the influence of staff absenteeism on patient satisfaction using
      the indicators available in management reports. BACKGROUND: Among factors
      explaining patient satisfaction, human resource indicators have been studied
      widely in terms of burnout or job satisfaction, but there have not been many
      studies related to absenteeism indicators. METHOD: A multilevel analysis was
      conducted using two routinely compiled databases from 2010 in the clinical
      departments of a university hospital (France). The staff database monitored
      absenteeism for short-term medical reasons (5 days or less), non-medical reasons
      and absences starting at the weekend. The patient satisfaction database was
      established at the time of discharge. RESULTS: Patient satisfaction related to
      relationships with staff was significantly and negatively correlated with nurse
      absenteeism for non-medical reasons (P < 0.05) and with nurse absenteeism
      starting at weekends (P < 0.05). Patient satisfaction related to the hospital
      environment was significantly and negatively correlated with nurse assistant
      absenteeism for short-term medical reasons (P < 0.05). CONCLUSION: Our findings
      seem to indicate that patient satisfaction is linked to staff absenteeism and
      should lead to a better understanding of the impact of human resources on patient
      satisfaction. IMPLICATIONS FOR NURSING MANAGEMENT: To enhance patient
      satisfaction, managers need to find a way to reduce staff absenteeism, in order
      to avoid burnout and to improve the atmosphere in the workplace.

PMID- 24581232
TI  - Angiotensin converting enzyme 2/Ang-(1-7)/mas axis protects brain from ischemic
      injury with a tendency of age-dependence.
AB  - BACKGROUND: The angiotensin (Ang) converting enzyme 2 (ACE2)/Ang-(1-7)/Mas
      receptor pathway is an important component of the renin-angiotensin system and
      has been suggested to exert beneficial effects in ischemic stroke. AIMS: This
      study explored whether the ACE2/Ang-(1-7)/Mas pathway has a protective effect on
      cerebral ischemic injury and whether this effect is affected by age. METHODS: We
      used three-month and eight-month transgenic mice with neural over-expression of
      ACE2 (SA) and their age-matched nontransgenic (NT) controls. Neurological
      deficits and ischemic stroke volume were determined following middle cerebral
      artery occlusion (MCAO). In oxygen and glucose deprivation (OGD) experiments on
      brain slices, the effects of the Mas receptor agonist (Ang1-7) or antagonist
      (A779) on tissue swelling, Nox2/Nox4 expression reactive oxygen species (ROS)
      production and cell death were measured. RESULTS: (1) Middle cerebral artery
      occlusion -induced ischemic injury and neurological deficit were reduced in SA
      mice, especially in eight-month animals; (2) OGD-induced tissue swelling and cell
      death were decreased in SA mice with a greater reduction seen in eight-month
      mice; (3) Ang-(1-7) and A779 had opposite effects on OGD-induced responses, which
      correlated with changes in Nox2/Nox4 expression and ROS production. CONCLUSIONS:
      Angiotensin converting enzyme 2/Ang-(1-7)/Mas axis protects brain from ischemic
      injury via the Nox/ROS signaling pathway, with a greater effect in older animals.

PMID- 24581234
TI  - Evidence for non-neutralizing autoantibodies against IL-10 signalling components
      in patients with inflammatory bowel disease.
AB  - BACKGROUND: Inflammatory bowel disease constitutes a heterogeneous group of
      conditions, whose aetiology is only partly understood. The prevailing hypothesis
      on its pathogenesis is that IBD is the result of an inadequate immune response to
      the resident bacterial flora of the intestine. An autoimmune background, however,
      has been discussed since the 1950s. Lately, it has been shown that failures in
      interleukin-10 (IL-10) signalling due to IL-10- and IL-10 receptor (IL-10R)
      mutations result in IBD. Our study aimed at investigating the existence of
      inhibitory autoantibodies against IL-10 and IL-10R in IBD patients capable of
      down-modulating IL-10 signalling thereby mimicking IL-10 or IL-10R deficiency.
      RESULTS: Thirteen IBD patients had IgG autoantibodies against IL-10, IL-10RA
      and/or IL-10RB, and three patients had IgA autoantibodies against IL-10. However,
      the absolute OD values of the serum antibodies measured by ELISA were low, there
      was overall no significant difference between patients and controls, and positive
      sera had no neutralizing activity. CONCLUSION: No evidence for an involvement of
      autoantibodies against IL-10 or IL-10R in the pathogenesis of inflammatory bowel
      disease could be established.

PMID- 24581236
TI  - Abstracts of the 16th ESOT Congress, 8-11 September 2013, Vienna, Austria.

PMID- 24581235
TI  - Recommendations for penicillin skin testing in Taiwan.

PMID- 24581240
TI  - The Wound Healing Society celebrates 25 years.

PMID- 24581239
TI  - Acylated and unacylated ghrelin inhibit doxorubicin-induced apoptosis in skeletal
      muscle.
AB  - AIM: Doxorubicin, a potent chemotherapeutic drug, has been demonstrated
      previously as an inducer of apoptosis in muscle cells. Extensive induction of
      apoptosis may cause excessive loss of muscle cells and subsequent functional
      decline in skeletal muscle. This study examined the effects of acylated ghrelin,
      a potential agent for treating cancer cachexia, on inhibiting apoptotic
      signalling in doxorubicin-treated skeletal muscle. Unacylated ghrelin, a form of
      ghrelin that does not bind to GHSR-1a, is also employed in this study to examine
      the GHSR-1a signalling dependency of the effects of ghrelin. METHODS: Adult
      C57BL/6 mice were randomly assigned to saline control (CON), doxorubicin (DOX),
      doxorubicin with treatment of acylated ghrelin (DOX+Acylated Ghrelin) and
      doxorubicin with treatment of unacylated ghrelin (DOX+Unacylated Ghrelin). Mice
      in all groups that involved DOX were intraperitoneally injected with 15 mg of
      doxorubicin per kg body weight, whereas mice in CON group received saline as
      placebo. Gastrocnemius muscle tissues were harvested after the experimental
      period for analysis. RESULTS: The elevation of apoptotic DNA fragmentation and
      number of TUNEL-positive nuclei were accompanied with the upregulation of Bax in
      muscle after exposure to doxorubicin, but all these changes were neither seen in
      the muscle treated with acylated ghrelin nor unacylated ghrelin after doxorubicin
      exposure. Protein abundances of autophagic markers including LC3 II-to-LC3 I
      ratio, Atg12-5 complex, Atg5 and Beclin-1 were not altered by doxorubicin but
      were upregulated by the treatment of either acylated or unacyated ghrelin.
      Histological analysis revealed that the amount of centronucleated myofibres was
      elevated in doxorubicin-treated muscle while muscle of others groups showed
      normal histology. CONCLUSIONS: Collectively, our data demonstrated that acylated
      ghrelin administration suppresses the doxorubicin-induced activation of apoptosis
      and enhances the cellular signalling of autophagy. The treatment of unacylated
      ghrelin has similar effects as acylated ghrelin on apoptotic and autophagic
      signalling, suggesting that the effects of ghrelin are probably mediated through
      a signalling pathway that is independent of GHSR-1a. These findings were
      consistent with the hypothesis that acylated ghrelin inhibits doxorubicin-induced
      upregulation of apoptosis in skeletal muscle while treatment of unacylated
      ghrelin can achieve similar effects as the treatment of acylated ghrelin. The
      inhibition of apoptosis and enhancement of autophagy induced by acylated and
      unacylated ghrelin might exert myoprotective effects on doxorubicin-induced
      toxicity in skeletal muscle.

PMID- 24581241
TI  - Paracrine anti-fibrotic effects of neonatal cells and living cell constructs on
      young and senescent human dermal fibroblasts.
AB  - Senescent cells observed in the area of chronic wounds have been proposed to
      affect wound healing. Therapeutic approaches against chronic wounds include,
      among others, the local application of living cell constructs (LCCs), containing
      fibroblasts and/or keratinocytes. Accordingly, the aim of the present work was to
      examine the effects of factors secreted by early passage neonatal fibroblasts and
      LCCs--in the form of a conditioned medium (CM)--on senescent adult dermal
      fibroblasts regarding functions related to the healing process, i.e., cell
      proliferation, alpha-smooth muscle actin and metalloproteinase expression, and
      collagen synthesis. Target cells were fibroblasts senescent either due to
      subsequent divisions (replicative senescence) or due to an exogenous stress
      (stress-induced premature senescence). No effect on the proliferation of
      senescent fibroblasts was observed, as expected. All CMs were found to inhibit
      overall collagen synthesis both in early passage and in senescent fibroblasts.
      The LCC-derived CM was found to be more potent than fibroblast-derived CMs and,
      furthermore, to inhibit alpha-smooth muscle actin expression. In conclusion,
      these results may indicate anti-contractile and anti-fibrotic activities of
      factor(s) secreted by neonatal skin fibroblasts, and more intensely by LCCs on
      adult donor-derived fibroblasts. These activities seem to persist during
      senescence of the target cells.

PMID- 24581244
TI  - A parthenogenetic maternal and double paternal contribution to an ovotesticular
      disorder of sex development.
AB  - BACKGROUND: An ovotesticular disorder of sex development (OT-DSD) was rarely
      found in human. The mechanism causing such condition is poorly understood. We
      hereby reported a 11-year-old child with OT-DSD and a karyotype 46,XX/46,XY, a
      single maternal and double paternal genetic contribution to the patient. RESULTS:
      Fluorescence in situ hybridization (FISH), blood grouping, HLA (human leukocyte
      antigen) haplotyping and a genome-wide scanning of lymphocytes with 398 short
      tandem repeat microsatellite markers were performed to investigate the origin of
      the cell lines concerned. ABO typing revealed that two populations of red cells
      were in the patient, which were group A and group B, both from paternal alleles.
      HLA haplotyping showed the patient had three haplotypes. Haplotype 1 was
      inherited from maternity, haplotype 2 and 3 were from paternity. The STR
      microsatellite analysis showed 25 of the 74 fully informative markers in both
      parents, three alleles were inherited: one of them was from mother, another two
      were from father. Seventeen of the thirty-eight paternal markers, the patient
      inherited two paternal alleles. For 121 informative maternal markers, the patient
      had a single maternal allele. There were two distinct alleles in locus DXS6810
      and DXS1073 on X-chromosome, in which one was from the mother and the other from
      the father. CONCLUSIONS: The patient was a single maternal and double paternal
      genetic, which was a type of a parthenogenetic division of a maternal haploid
      nucleus into two identical nuclei, followed by fertilization by two spermatozoa
      and fusion of the two zygotes into a single individual at the early embryonic
      stage. To the best of our knowledge, this is the oldest OT-DSD case of
      parthenogenetic chimerism. These data provide additional evidence that a
      parthenogenetic maternal and double paternal contribution causes 46,XX/46,XY OT
      DSD.

PMID- 24581245
TI  - Study protocol for a comparative effectiveness trial of two parent training
      programs in a fee-for-service mental health clinic: can we improve mental health
      services to low-income families?
AB  - BACKGROUND: Untreated behavioral and mental health problems beginning in early
      childhood are costly problems affecting the long-term health and wellbeing of
      children, their families, and society. Although parent training (PT) programs
      have been demonstrated to be a cost-effective intervention modality for treating
      childhood behavior problems, they have been less effective for children from low
      income and underserved racial and ethnic populations. The purpose of this
      randomized trial is to compare the effectiveness, cost, and social validity of
      two manualized evidence-based PT programs that were developed and tested on
      different populations and employ different delivery models: (1) The Chicago
      Parent Program (CPP), a group-based program developed in collaboration with a
      community advisory board of African-American and Latino parents; and (2) Parent
      Child Interaction Therapy (PCIT), an individualized parent-child coaching model
      considered to be 'the gold standard' for parents of children with externalizing
      behavior problems. METHODS: This trial uses an experimental design with
      randomization of parents seeking behavioral treatment for their 2- to 5-year-old
      children at a mental health clinic in Baltimore, MD (80% African-American or
      multi-racial; 97% receiving Medicaid). Using block randomization procedures, 262
      parents are randomized to CPP or PCIT. Clinicians (n=13) employed in the mental
      health clinic and trained in CPP or PCIT are also recruited to participate.
      Primary outcomes of interest are reductions in child behavior problems,
      improvements in parenting, perceived value of the interventions from the
      perspective of parents and clinicians, and cost. Parent distress and family
      social risk are assessed as modifiers of treatment effectiveness. We hypothesize
      that CPP will be at least as effective as PCIT for reducing child behavior
      problems and improving parenting but the programs will differ on cost and their
      social validity as perceived by parents and clinicians. DISCUSSION: This is the
      first study to compare the effectiveness of a PT program originally designed with
      and for parents from underserved racial and ethnic populations (CPP) against a
      well-established program considered to be the 'the gold standard' (PCIT) with a
      high-risk population of parents. Challenges related to conducting a randomized
      trial in a fee-for-service mental health clinic serving urban, low-income
      families are discussed. TRIAL REGISTRATION: NCT01517867.

PMID- 24581247
TI  - Rare coagulation factor deficiencies: a countrywide screening data from India.
AB  - As compared to haemophilia, although the clinical features and the management
      strategies for rare coagulation factor deficiencies are discussed, little is
      known about them. This study was undertaken to assess the distribution, clinical
      presentation and treatment of patients with rare coagulation factor deficiency
      disorders in a cross-sectional population of India. Blood samples and other
      clinical details from patients suspected of rare coagulation factor deficiencies
      were collected by the Haemophilia Treatment Centers across India and were
      diagnosed at National Institute of Immunohaematology, Mumbai. A total of 321
      cases of rare clotting factor deficiencies were diagnosed, of which 88% were
      severe, 10% moderate and 2% mild. Commonest deficiency encountered was factor
      XIII (FXIII) (30%) followed by FX (15.6%), FVII (15%), fibrinogen (12.1%), FXI
      (9%), combined V and VIII deficiency (5.6%) and congenital multiple vitamin K
      dependent coagulation factor deficiency (MCFD, 2.1%). Major representation of
      these deficiencies was from Southern and Western India (82%). Mucocutaneous
      bleeding was the commonest clinical presentation (59%); intracranial (IC)
      haemorrhage was seen in 18% of the patients; menorrhagia was an important
      clinical pointer in women in the reproductive age group (78%); 8% of the severe
      cases had no history of bleeding and 73% of the FXIII deficiency cases had
      umbilical stump bleeding. The major therapeutic products used was fresh frozen
      plasma (64%), cryoprecipitate (15%), whole blood (15%), antifibrinolytics (5%)
      and recombinant FVIIa (1%). A distinct pattern in the distribution of rare
      clotting factor deficiencies was observed which was based on multiple factors
      that include ethnicity and the available diagnostic facilities in different
      regions of this vast country. 

PMID- 24581246
TI  - Inflammatory and cytotoxic effects of acrolein, nicotine, acetylaldehyde and
      cigarette smoke extract on human nasal epithelial cells.
AB  - BACKGROUND: Cigarette smoke induces a pro-inflammatory response in airway
      epithelial cells but it is not clear which of the various chemicals contained
      within cigarette smoke (CS) should be regarded as predominantly responsible for
      these effects. We hypothesised that acrolein, nicotine and acetylaldehyde,
      important chemicals contained within volatile cigarette smoke in terms of
      inducing inflammation and causing addiction, have immunomodulatory effects in
      primary nasal epithelial cell cultures (PNECs). METHODS: PNECs from 19 healthy
      subjects were grown in submerged cultures and were incubated with acrolein,
      nicotine or acetylaldehyde prior to stimulation with Pseudomonas aeruginosa
      lipopolysaccharide (PA LPS). Experiments were repeated using cigarette smoke
      extract (CSE) for comparison. IL-8 was measured by ELISA, activation of NF-kappaB
      by ELISA and Western blotting, and caspase-3 activity by Western blotting.
      Apoptosis was evaluated using Annexin-V staining and the terminal transferase
      mediated dUTP nick end-labeling (TUNEL) method. RESULTS: CSE was pro-inflammatory
      after a 24 h exposure and 42% of cells were apoptotic or necrotic after this
      exposure time. Acrolein was pro-inflammatory for the PNEC cultures (30 MUM
      exposure for 4 h inducing a 2.0 fold increase in IL-8 release) and also increased
      IL-8 release after stimulation with PA LPS. In contrast, nicotine had anti
      inflammatory properties (0.6 fold IL-8 release after 50 MUM exposure to nicotine
      for 24 h), and acetylaldehyde was without effect. Acrolein and nicotine had
      cellular stimulatory and anti-inflammatory effects respectively, as determined by
      NF-kappaB activation. Both chemicals increased levels of cleaved caspase 3 and
      induced cell death. CONCLUSIONS: Acrolein is pro-inflammatory and nicotine anti
      inflammatory in PNEC cultures. CSE induces cell death predominantly by apoptotic
      mechanisms.

PMID- 24581248
TI  - Transport properties of carboxylated nitrile butadiene rubber (XNBR)-nanoclay
      composites; a promising material for protective gloves in occupational exposures.
AB  - This study was conducted in response to one of the research needs of National
      Institute for Occupational Safety and Health (NIOSH), i.e. the application of
      nanomaterials and nanotechnology in the field of occupational safety and health.
      In order to fill this important knowledge gap, the equilibrium solubility and
      diffusion of carbon tetrachloride and ethyl acetate through carboxylated nitrile
      butadiene rubber (XNBR)-clay nanocomposite, as a promising new material for
      chemical protective gloves (or barrier against the transport of organic solvent
      contaminant), were examined by swelling procedure. Near Fickian diffusion was
      observed for XNBR based nanocomposites containing different amounts of nanoclay.
      Decontamination potential is a key factor in development of a new material for
      reusable chemical protective gloves applications, specifically for routine or
      highly toxic exposures. A thermal decontamination regime for nanocomposite was
      developed for the first time. Then, successive cycles of exposure/decontamination
      for nanocomposite were performed to the maximum 10 cycles for the first time.
      This result confirms that the two selected solvents cannot deteriorate the rubber
      nanoclay interaction and, therefore, such gloves can be reusable after
      decontamination. 

PMID- 24581249
TI  - Evaluation of a universal long-lasting insecticidal net (LLIN) distribution
      campaign in Ghana: cost effectiveness of distribution and hang-up activities.
AB  - BACKGROUND: Between May 2010 and October 2012, approximately 12.5 million long
      lasting insecticidal nets (LLINs) were distributed through a national universal
      mass distribution campaign in Ghana. The campaign included pre-registration of
      persons and sleeping places, door-to-door distribution of LLINs with 'hang-up'
      activities by volunteers and post-distribution 'keep-up' behaviour change
      communication activities. Hang-up activities were included to encourage high and
      sustained use. METHODS: The cost and cost-effectiveness of the LLIN Campaign were
      evaluated using a before-after design in three regions: Brong Ahafo, Central and
      Western. The incremental cost effectiveness of the 'hang-up' component was
      estimated using reported variation in the implementation of hang-up activities
      and LLIN use. Economic costs were estimated from a societal perspective assuming
      LLINs would be replaced after three years, and included the time of unpaid
      volunteers and household contributions given to volunteers. RESULTS: Across the
      three regions, 3.6 million campaign LLINs were distributed, and 45.5% of
      households reported the LLINs received were hung-up by a volunteer. The financial
      cost of the campaign was USD 6.51 per LLIN delivered. The average annual economic
      cost was USD 2.90 per LLIN delivered and USD 6,619 per additional child death
      averted by the campaign. The cost-effectiveness of the campaign was sensitive to
      the price, lifespan and protective efficacy of LLINs.Hang-up activities
      constituted 7% of the annual economic cost, though the additional financial cost
      was modest given the use of volunteers. LLIN use was greater in households in
      which one or more campaign LLINs were hung by a volunteer (OR=1.57; 95% CI=1.09,
      2.27; p=0.02). The additional economic cost of the hang-up activities was USD
      0.23 per LLIN delivered, and achieved a net saving per LLIN used and per death
      averted. CONCLUSION: In this campaign, hang-up activities were estimated to be
      net saving if hang-up increased LLIN use by 10% or more. This suggests hang-up
      activities can make a LLIN campaign more cost-effective.

PMID- 24581250
TI  - Arthroscopic and sports medicine science: looking beyond the level of evidence
      (for now).

PMID- 24581251
TI  - Author's reply: To PMID 22738752.

PMID- 24581252
TI  - Area-based determination of bone loss using the glenoid arc angle.

PMID- 24581253
TI  - Properties of biologic scaffolds and their response to mesenchymal stem cells.
AB  - PURPOSE: The purpose of this study was to examine, in vitro, the cellular
      response of human mesenchymal stem cells (MSCs) to sample types of commercially
      available scaffolds in comparison with control, native tendon tissue (fresh
      frozen rotator cuff tendon allograft). METHODS: MSCs were defined by (1) colony
      forming potential; (2) ability to differentiate into tendon, cartilage, bone, and
      fat tissue; and (3) fluorescence-activated cell sorting analysis (CD73, CD90,
      CD45). Samples were taken from fresh-frozen human rotator cuff tendon
      (allograft), human highly cross-linked collagen membrane (Arthroflex; LifeNet
      Health, Virginia Beach, VA), porcine non-cross-linked collagen membrane
      (Mucograft; Geistlich Pharma, Lucerne, Switzerland), a human platelet-rich fibrin
      matrix (PRF-M), and a fibrin matrix based on platelet-rich plasma (ViscoGel;
      Arthrex, Naples, FL). Cells were counted for adhesion (24 hours), thymidine assay
      for cell proliferation (96 hours), and live/dead stain for viability (168 hours).
      Histologic analysis was performed after 21 days, and the unloaded scaffolds were
      scanned with electron microscopy. RESULTS: MSCs were successfully differentiated
      into all cell lines. A significantly greater number of cells adhered to both the
      non-cross-linked porcine collagen scaffold and PRF-M. Cell activity
      (proliferation) was significantly higher in the non-cross-linked porcine collagen
      scaffold compared with PRF-M and fibrin matrix based on platelet-rich plasma.
      There were no significant differences found in the results of the live/dead
      assay. CONCLUSIONS: Significant differences in the response of human MSCs to
      biologic scaffolds existed. MSC adhesion, proliferation, and scaffold morphology
      evaluated by histologic analysis and electron microscopy varied throughout the
      evaluated types of scaffolds. Non-cross-linked porcine collagen scaffolds showed
      superior results for cell adhesion and proliferation, as well as on histologic
      evaluation. CLINICAL RELEVANCE: This study enables the clinician and scientist to
      choose scaffold materials according to their specific interaction with MSCs.

PMID- 24581254
TI  - Hip arthroscopy: prevalence of intra-articular pathologic findings after
      traumatic injury of the hip.
AB  - PURPOSE: The purpose of this study was to document and compare the incidence of
      intra-articular hip pathologic findings identified using arthroscopy versus
      conventional imaging in patients with acute trauma to the hip. METHODS: This was
      a blinded prospective case series study designed to review the incidence of intra
      articular pathologic disorders in patients with post-traumatic injury between the
      ages of 18 and 65 years who were referred to a single surgeon. Injuries included
      hip dislocation, proximal femur fracture, pelvic ring fracture, acetabular
      fracture, penetrating injury (gunshot wound), and soft tissue injury.
      Preoperative radiographs, computed tomographic (CT) scans, or magnetic resonance
      imaging/magnetic resonance angiography (MRI/MRA) scans (or a combination of
      these) were obtained. Findings were documented and compared with intraoperative
      findings. RESULTS: A total of 29 post-traumatic hips were enrolled in this study.
      Hip arthroscopy identified 17 of 29 hips (59%) as having loose bodies, 11 of 29
      (38%) hips as having an intra-articular step deformity, 14 of 29 (49%) hips as
      having an osteochondral lesion, and 27 of 29 (93%) hips as having a labral tear.
      Plain radiographs and CT scans yielded low sensitivity when compared with
      arthroscopy for the identification of loose bodies and step deformities. MRI/MRA
      comparison with arthroscopic findings suggest that MRI/MRA is an accurate tool
      for identification of labral tears, because 91% of tears seen on arthroscopy were
      also identified by MRI/MRA. In 4 hips, however, MRI/MRA failed to identify
      osteochondral lesions that were subsequently identified by arthroscopy.
      CONCLUSIONS: Traumatic injuries of the hip result in substantial intra-articular
      pathologic findings, including loose bodies, labral tears, step deformities, and
      osteochondral lesions. The arthroscope is a powerful tool in identifying these
      injuries. Plain radiographs and CT scans appear to underestimate the true
      incidence of loose bodies and step deformities within the joint when compared
      with hip arthroscopy after a traumatic injury of the hip. LEVEL OF EVIDENCE:
      Level IV, diagnostic case series.

PMID- 24581255
TI  - Discoid lateral meniscus tears and concomitant articular cartilage lesions in the
      knee.
AB  - PURPOSE: The purpose of this study was to investigate the relation between
      isolated discoid lateral meniscus (DLM) tears and the presence of articular
      cartilage lesions. METHODS: From January 2010 to January 2012, 252 consecutive
      patients diagnosed with an isolated DLM tear during an arthroscopic procedure
      were included in this study. Demographic variables, including gender, age, body
      mass index (BMI), traumatic history, time course, and date of the DLM tear, were
      recorded. The relation between DLM tears and the presence of articular cartilage
      lesions was analyzed by the chi(2) test. Logistic regression analysis was used to
      analyze the relation between these variables and articular cartilage lesions.
      RESULTS: Of the patients with DLM tears, 67 (26.6%) also had articular cartilage
      lesions. The most common type of DLM tear was the complex tear (46.8%). The most
      common location of articular cartilage lesions was the lateral tibial plateau
      (11.6%). Lesions on the opposing articular surfaces of the lateral compartment
      and patellofemoral joint of the knee were found in 12 patients (4.8%) and 11
      patients (4.4%), respectively. There were no significant differences in the
      incidences of articular cartilage lesions in patients with different types of DLM
      tears (P > .05). Gender (odds ratio [OR], 2.289; P = .012), BMI (OR, 1.991; P =
      .023), and time course (OR, 2.050; P = .034) were significantly associated with
      articular cartilage lesions. CONCLUSIONS: DLM tears were more common in the
      context of degenerative tears. There was no significant difference in the
      incidence of articular cartilage lesions among patients with different types of
      DLM tears. Female patients, patients with a BMI greater than 23.0 kg/m(2), or
      patients with a time course of greater than 6 months were more frequently
      observed to also have articular cartilage lesions. LEVEL OF EVIDENCE: Level IV,
      therapeutic case series.

PMID- 24581256
TI  - Serial assessment of weight-bearing lower extremity alignment radiographs after
      open-wedge high tibial osteotomy.
AB  - PURPOSE: The purpose of this study was to perform a serial assessment of the
      radiologic parameters of the mechanical axis (MA) and the weight-bearing line
      (WBL) using a weight-bearing anteroposterior (AP) long-standing view of the lower
      extremity to determine whether the postoperative MA and WBL change with time.
      METHODS: A total of 90 consecutive lower limbs were examined retrospectively from
      a weight-bearing AP long-standing view of the lower extremity obtained from 120
      patients who underwent open-wedge high tibial osteotomy (OWHTO). A total of 30
      patients were excluded because of (1) complications (7 patients) such as bone
      graft collapse or broken screws, malunion, or nonunion arising after surgery and
      (2) no acquisition of a regular series of weight-bearing AP long-standing views
      of the lower extremity (23 patients). The AP long-standing view of the lower
      extremity was taken, and weight-bearing AP long-standing views of the lower
      extremity at 1 month, 6 months, 1 year, and 2 years postoperatively were used for
      assessment of serial change. The Picture Archiving Communication System
      (Marotech, Inc, St-Augustin-de-Desmaures, Quebec, Canada) was used for radiologic
      measurements of the WBL ratio and MA. Serial changes were compared between 1
      month, 6 months, 1 year, and 2 years postoperatively. RESULTS: The WBL ratio
      progressively shifted medially, with significant changes at all time points until
      1 year postoperatively (1 month to 6 months, P = .04; 6 months to 1 year, P =
      .04; 1 year to 2 years, P = .22). Even though the MA angle showed a similar
      decreasing trend, it showed no statistical difference (P > .05). CONCLUSIONS:
      This study showed that after OWHTO, the WBL shifts progressively medially until 1
      year postoperatively. LEVEL OF EVIDENCE: Level IV, diagnostic study.

PMID- 24581257
TI  - Tunnel volume enlargement after posterior cruciate ligament reconstruction:
      comparison of achilles allograft with mixed autograft/allograft--a prospective
      computed tomography study.
AB  - PURPOSE: The purpose of this study was to evaluate and compare femoral and tibial
      tunnel volume enlargement (TVE) after arthroscopic posterior cruciate ligament
      (PCL) reconstruction by remnant bundle preservation using Achilles allograft or
      mixed graft. METHODS: Seventy-eight patients undergoing primary arthroscopic
      single-bundle PCL reconstruction were initially included. Fifty-six of these
      patients underwent follow-up for a minimum of 1 year postoperatively and were
      divided into 2 groups: group A received Achilles allograft (n = 27), and group B
      received mixed graft (n = 29). The clinical evaluation included the International
      Knee Documentation Committee rating, Lysholm score, Tegner activity score, and
      Telos stress test (Telos, Weiterstadt, Germany). All of the patients were
      evaluated for TVE by computed tomography scanning at the 1-year follow-up; the
      results were compared with the data from 1 week postoperatively. A volume
      increment of more than 44%, which indicates 2 mm of widening of the tunnel
      diameter, was defined as TVE. RESULTS: The overall incidence of TVE after single
      bundle PCL reconstruction was 3.6% (2 of 56 patients) for the femoral tunnel and
      5.4% (3 of 56 patients) for the tibial tunnel. The overall mean tunnel difference
      between 1 week postoperatively and the final follow-up was 12.0% for the femoral
      tunnel and 10.6% for the tibial tunnel. The mean femoral TVE was 10.1% in group A
      and 13.8% in group B; the mean tibial TVE was 9.9% in group A and 11.2% in group
      B. These differences were not statistically significant. The functional outcome
      was improved in both groups, showing no statistical difference at the 1-year
      follow-up. CONCLUSIONS: The femoral and tibial TVE caused by single-bundle PCL
      reconstruction using the remnant bundle-preservation technique showed no
      significant differences between the Achilles allograft and the mixed graft over a
      short-term follow-up. Furthermore, the overall incidence of TVE in PCL
      reconstruction in this study was low. LEVEL OF EVIDENCE: Level II, prospective
      comparative study.

PMID- 24581258
TI  - Biomechanical analysis of knee laxity with isolated anteromedial or
      posterolateral bundle-deficient anterior cruciate ligament.
AB  - PURPOSE: The purpose of this study was to clarify the changes in the kinematics
      of the knee that result from isolated deficiency of the anteromedial (AM) or
      posterolateral (PL) bundle. METHODS: Fourteen cadaveric knees were mounted in a 6
      df rig and tested using the following 5 loading conditions: 90-N anterior and
      posterior tibial loads, 5-Nm internal and external tibial torques, and a
      simulated pivot-shift test. Tibiofemoral kinematics during flexion-extension was
      recorded with an optical tracking system for (1) intact knees, (2) knees in which
      the isolated AM bundle was cut, (3) knees in which the isolated PL bundle was
      cut, and (4) anterior cruciate ligament (ACL)-deficient knees. The distances
      between the femoral and tibial attachments of the AM and PL bundles of the ACL
      were also calculated. RESULTS: Anterior translation laxity under an anterior
      tibial load, rotational laxity under an internal tibial torque, and anterior
      translation laxity under pivot-shift loading were significantly different between
      the knees with AM and PL bundle deficiencies (P < .024), but the changes were
      small: less than 3 mm or 1.5 degrees . The AM bundle distance increased
      significantly more after an AM bundle tear (P = .004) than after a PL bundle tear
      in flexion. Cutting the PL bundle did not have a significant effect on the
      lengths between the bundle attachments. CONCLUSIONS: An isolated AM or PL bundle
      tear caused a small increase in laxity (<3 mm or <1.5 degrees ). CLINICAL
      RELEVANCE: If there is a clinically identifiable increase in laxity, then--in
      addition to the isolated tear of the AM or PL bundle--there must also be a tear
      of the other bundle of the ACL, or at least a partial tear.

PMID- 24581259
TI  - Acute anterior cruciate ligament reconstruction with an augmented remnant repair:
      a comparative macroscopic and biomechanical study in an animal model.
AB  - PURPOSE: Our purpose was (1) to compare the structural integrity and healing
      capacity of the acutely repaired anterior cruciate ligament (ACL) remnants and
      (2) to determine whether the short-term postoperative biomechanical results of
      the acute remnant-repairing anterior cruciate ligament reconstruction (ACLR) were
      superior to the conventional ACLR. METHODS: An acute complete ACL femoral
      detachment model was created in 50 rabbits. The rabbits were immediately randomly
      allocated into the remnant-repairing ACLR group (group 1, n = 25) and the
      conventional ACLR group (group 2, n = 25). Each animal in both groups was
      subjected to unilateral ACLR with semitendinosus tendon autografts. During ACLR,
      the ACL remnants were acutely repaired with the femoral-tensioning technique in
      group 1, whereas the ACL remnants were debrided in group 2. The outcomes of the
      remnant were macroscopically evaluated in group 1. The remnant's structural
      integrity and remnant-to-graft healing capacity were divided into 3 categories
      (grade A, good; grade B, fair; or grade C, poor) according to 2 distinct
      criteria. Biomechanical tests including the anterior tibial translation test at
      30 degrees  and 90 degrees  of knee flexion and tensile tests were compared
      between groups. All the macroscopic evaluations and biomechanical tests were
      performed postoperatively at week 12. RESULTS: The macroscopic evaluations of the
      ACL remnants in group 1 (n = 25) showed that the remnants' structural integrity
      was grade A (well-maintained continuity with an adequate amount of tissue and
      tension on probing) in 10 specimens (40%), grade B (fairly maintained continuity
      with thin and slack fibers detected) in 5 (20%), and grade C (resorption with no
      remnant left in situ) in 10 (40%). The remnant-to-graft healing capacities among
      the specimens with surviving remnants (grades A and B for structural integrity, n
      = 15) were all classified as grade C (an obvious remnant-to-graft interval
      through the entire length of the graft). For the biomechanical tests, there were
      no significant differences between the groups (25 in each group) with respect to
      the anterior tibial translation test at 30 degrees  (P = .15) and 90 degrees  (P
      = .91) of knee flexion and stiffness (P = .66), ultimate failure load (P = .11),
      and elongation at failure (P = .92). CONCLUSIONS: In our rabbit model of ACL
      femoral detachment, the acutely repaired ACL remnants showed a high resorption
      rate, low healing capacity, and poor biomechanical properties. The acute remnant
      repairing ACLR had no evident superiority over the conventional ACLR in rabbits.
      CLINICAL RELEVANCE: The findings did not support the contention that the remnant
      repairing ACLR, even performed in the acute setting, could produce better
      postoperative knee joint stability outcomes than the conventional ACLR.

PMID- 24581260
TI  - Can arthroscopically harvested synovial stem cells be preferentially sorted using
      stage-specific embryonic antigen 4 antibody for cartilage, bone, and adipose
      regeneration?
AB  - PURPOSE: The aim of this study was to investigate the relation between stage
      specific embryonic antigen 4 (SSEA4) expression and synovium-derived stem cell
      (SDSC) lineage differentiation. METHODS: Human SDSCs were collected during
      arthroscopic surgery from 4 young patients with anterior cruciate ligament
      injuries. Passage 2 SDSCs were sorted by fluorescence-activated cell sorting
      using phycoerythrin-conjugated monoclonal antibody against SSEA4 into 3 groups:
      SSEA4(+) cells, SSEA4(-) cells, and unsorted control cells. After 1 more passage,
      expanded cells from each group were evaluated for SSEA4 expression by use of flow
      cytometry as well as multilineage differentiation capacities, including
      chondrogenesis, adipogenesis, and osteogenesis, using biochemical analysis,
      histologic analysis, immunostaining, and real-time polymerase chain reaction.
      RESULTS: After cell sorting, 1 more passage expansion decreased SSEA4(+) cells
      from 99.8% to 79.2% and increased SSEA4(-) cells from 4.4% to 53.3% compared with
      70.3% in the unsorted cell population. SSEA4(-) SDSCs with a lower cell
      proliferation exhibited higher chondrogenic potential (in terms of the ratio of
      glycosaminoglycan to DNA [P < .001] and COL2A1 [type II collagen] messenger RNA
      [mRNA] [P < .001]) and adipogenic potential (in terms of oil red O staining and
      quantitative assay [P = .007], LPL [lipoprotein lipase] mRNA [P = .005], and CEBP
      [CCAAT/enhancer-binding protein alpha] mRNA [P = .010]). In contrast, SSEA4(+)
      SDSCs retained cell expansion and enhanced osteogenic capacity, as evidenced by
      intense calcium deposition stained by alizarin red S and a significantly elevated
      expression of OPN (osteopontin) mRNA (P = .007). CONCLUSIONS: In this study, for
      the first time, we showed the benefit of using the surface marker SSEA4 in SDSCs
      to preferentially sort a mixed population of cells. SSEA4(+) SDSCs indicated a
      strong potential for osteogenesis rather than chondrogenesis and adipogenesis.
      CLINICAL RELEVANCE: SDSC-based mesenchymal tissue regeneration can be easily
      achieved by arthroscopic harvesting followed by quick cell sorting.

PMID- 24581261
TI  - Current status of evidence-based sports medicine.
AB  - PURPOSE: The purpose of this investigation is to determine the proportion of
      sports medicine studies that are labeled as Level I Evidence in 5 journals and
      compare the quality of surgical and nonsurgical studies using simple quality
      assessment tools (Consolidated Standards of Reporting Trials [CONSORT] and
      Jadad). METHODS: By use of PRISMA (Preferred Reporting Items for Systematic
      Reviews and Meta-Analyses) guidelines over the prior 2 years in the top 5
      (citation and impact factor based) sports medicine journals, only Level I
      Evidence studies were eligible for inclusion and were analyzed. All study types
      (therapeutic, prognostic, diagnostic, and economic) were analyzed. Study quality
      was assessed with the level of evidence, Jadad score, and CONSORT 2010
      guidelines. Study demographic data were compared among journals and between
      surgical and nonsurgical studies by use of chi(2), 1-way analysis of variance,
      and 2-sample Z tests. RESULTS: We analyzed 190 Level I Evidence studies (10% of
      eligible studies) (119 randomized controlled trials [RCTs]). Therapeutic,
      nonsurgical, single-center studies from the United States were the most common
      studies published. Sixty-two percent of studies reported a financial conflict of
      interest. The knee was the most common body part studied, and track-and
      field/endurance sports were the most common sports analyzed. Significant
      differences (P < .05) were shown in Jadad and CONSORT scores among the journals
      reviewed. Overall, the Jadad and CONSORT scores were 2.71 and 77%, respectively.
      No differences (P > .05) were shown among journals based on the proportion of
      Level I studies or appropriate randomization. Significant strengths and
      limitations of RCTs were identified. CONCLUSIONS: This study showed that Level I
      Evidence and RCTs comprise 10% and 6% of contemporary sports medicine literature,
      respectively. Therapeutic, nonsurgical, single-center studies are the most common
      publications with Level I Evidence. Significant differences across sports
      medicine journals were found in study quality. Surgical studies appropriately
      described randomization, blinding, and patient enrollment significantly more than
      nonsurgical studies. LEVEL OF EVIDENCE: Level I, systematic review of Level I
      studies.

PMID- 24581262
TI  - Recurrent instability after revision anterior shoulder stabilization surgery.
AB  - PURPOSE: The purpose of this study was to perform a systematic review of the
      literature to compare outcomes of revision anterior stabilization surgeries based
      on technique. This study also sought to compare the impact of bone defects on
      outcomes. METHODS: A systematic review of the electronic databases PubMed,
      Cochrane Central Register of Controlled Trials, and Scopus was performed in July
      2012 and March 2013. Of 345 articles identified in the search, 17 studies with
      Level I to IV Evidence satisfied the inclusion criteria and were analyzed
      according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta
      Analyses) guidelines. Recurrent instability was defined as redislocation,
      resubluxation, or a positive apprehensive test after revision surgery. Procedures
      were categorized as arthroscopic Bankart repair, open Bankart repair, Bristow
      Latarjet procedure, and other open procedures. RESULTS: In total, 388 shoulders
      were studied. Male patients comprised 74.1% of patients, 66.7% of cases involved
      the dominant shoulder, the mean age was 28.2 years, and the mean follow-up period
      was 44.2 months. The surgical procedures classified as "other open procedures"
      had the highest rate of recurrent instability (42.7%), followed by arthroscopic
      Bankart repair (14.7%), the Bristow-Latarjet procedure (14.3%), and open Bankart
      repair (5.5%). Inconsistent reporting of bone defects precluded drawing
      significant conclusions. CONCLUSIONS: A number of different procedures are used
      to address recurrent instability after a primary operation for anterior shoulder
      instability has failed. There is significant variability in the rate of recurrent
      instability after revision anterior shoulder stabilization surgery. LEVEL OF
      EVIDENCE: Level IV, systematic review of Level I to IV studies.

PMID- 24581263
TI  - The demographic characteristics of high-level and recreational athletes
      undergoing hip arthroscopy for femoroacetabular impingement: a sports-specific
      analysis.
AB  - PURPOSE: The purpose of this study was to determine differences in age, gender,
      and the need for bilateral surgery between high-level athletes grouped by sports
      with similar mechanical demands on the hip and recreational athletes undergoing
      hip arthroscopy for femoroacetabular impingement (FAI). METHODS: By use of a hip
      preservation center registry, a retrospective review of patients undergoing hip
      arthroscopy for FAI between March 2010 and April 2012 was performed. Athletes
      were categorized as high level (high school, collegiate, or professional) or
      recreational. We performed a subgroup analysis for high-level athletes, looking
      at differences among contact, cutting, impingement, overhead/asymmetric,
      endurance, and flexibility sports. RESULTS: The study included 288 high-level
      athletes and 334 recreational athletes. Being a high-level athlete was associated
      with a younger age (mean age, 20.2 years v 33.0 years; odds ratio, 0.69; P <
      .001) and male gender (61.5% v 53.6%; odds ratio, 1.75; P = .03). The percentage
      of high-level athletes undergoing bilateral surgery was higher than that of
      recreational athletes (28.4% v 15.9%); however, this association was found to be
      confounded by age on multivariate analysis. The most common sports for high-level
      athletes were soccer, hockey, and football. Athletes participating in cutting
      sports were significantly younger than athletes participating flexibility,
      contact, or impingement sports. CONCLUSIONS: When compared with recreational
      athletes undergoing arthroscopic treatment for FAI, high-level athletes are more
      likely to be younger, to be male, and to undergo bilateral surgery. When high
      level athletes are grouped by the mechanical demands placed on the hip by their
      sport, athletes participating in cutting sports are more likely to be younger
      than those in the other groups. LEVEL OF EVIDENCE: Level IV, case series.

PMID- 24581264
TI  - Deep venous thrombosis after knee arthroscopy: a systematic review and meta
      analysis.
AB  - PURPOSE: To establish a contemporary literature-based estimate of the incidence
      of deep venous thrombosis (DVT) after knee arthroscopic surgery. METHODS: We
      performed a systematic review and meta-analysis of the English language
      literature to assess the efficacy of prophylaxis to prevent DVT after knee
      arthroscopic surgery. Only randomized controlled trials (RCTs) or prospective
      studies were considered. Studies were excluded if they were not original
      prospective studies concerning DVT detected by imaging after knee arthroscopic
      surgery. We calculated pooled proportions of postoperative DVT and proximal DVT.
      RESULTS: Nine prospective uncontrolled studies and 4 RCTs were retrieved. Within
      them, the populations given low-molecular-weight heparin (LMWH) to prevent DVT
      had a 0.1% to 11.9% incidence of DVT, with an overall 36 DVTs identified (4
      proximal), averaging 1.8%. One hundred thirty-six DVTs (29 proximal) were
      indicated in the populations without prophylaxis, and the DVT incidence varied
      from 1.8% to 41.2%, averaging 6.8%. Of the RCTs, the pooled risk ratio for DVT to
      develop was 0.180 (range, 0.065 to 0.499) for those who had LMWH as prophylaxis.
      An absolute risk reduction of 1.2%--from 1.5% to 0.3%--for the development of
      proximal DVT was observed. CONCLUSIONS: Compared with patients who did not
      receive prophylaxis, the pooled risk ratio for the development of DVT was 0.18
      for those who had LMWH prophylaxis. The incidence of proximal DVT is very low
      after arthroscopic surgery regardless of receiving prophylaxis (4 of 2,184) or
      not (29 of 1,814). The rate of proximal DVT in total DVT occurrence can be
      markedly reduced from 21.3% (29 of 136) to 11.1% (4 of 36). LEVEL OF EVIDENCE:
      Level IV. This study is a meta-analysis of RCTs and a systematic review of Level
      IV studies.

PMID- 24581266
TI  - Abstracts of the 13th Annual Congress of the French Speaking Society of
      Transplantation, 11-14 December 2013, Marrakech, Morocco.

PMID- 24581265
TI  - Challenges of providing HIV care in general practice.
AB  - As the management of HIV changes and demand for HIV health services in primary
      care settings increases, new approaches to engaging the general practice
      workforce with HIV medicine are required. This paper reports on qualitative
      research conducted with 47 clinicians who provide HIV care in general practice
      settings around Australia, including accredited HIV s100 prescribers as well as
      other GPs and general practice nurses. Balanced numbers of men and women took
      part; less than one-quarter were based outside of urban metropolitan settings.
      The most significant workforce challenges that participants said they faced in
      providing HIV care in general practice were keeping up with knowledge, navigating
      low caseload and regional issues, balancing quality care with cost factors, and
      addressing the persistent social stigma associated with HIV. Strategic responses
      developed by participants to address these challenges included thinking more
      creatively about business and caseload planning, pursuing opportunities to share
      care with specialist clinicians, and challenging prejudiced attitudes amongst
      patients and colleagues. Understanding and supporting the needs of the general
      practice workforce in both high and low HIV caseload settings will be essential
      in ensuring Australia has the capacity to respond to emerging priorities in HIV
      prevention and care.

PMID- 24581267
TI  - Childhood tuberculosis and its treatment outcomes in Addis Ababa: a 5-years
      retrospective study.
AB  - BACKGROUND: Tuberculosis (TB) remains a significant public health problem leading
      to high morbidity and mortality both in adults and children. Reports on childhood
      TB and its treatment outcome are limited. In this retrospective study, we
      analyzed the epidemiology and treatment outcomes of TB among children in Addis
      Ababa. METHODS: Children registered for TB treatment over 5 years (2007 to 2011)
      were included in the analysis. Demographic and clinical data including treatment
      outcomes were extracted from TB unit registers of 23 health centers in Addis
      Ababa. Multivariate logistic regression was used to identify predictors of poor
      treatment outcomes. RESULTS: Among 41,254 TB patients registered for treatment at
      the 23 health centers, 2708 (6.6%) were children. Among children with TB, the
      proportions of smear positive PTB, smear negative PTB and EPTB were 9.6%, 43.0%
      and 47.4%, respectively. Treatment outcomes were documented for 95.2% of children
      of whom 85.5% were successfully treated while rates of mortality and defaulting
      from treatment were 3.3% and 3.8%, respectively. The proportion of children with
      TB tested for HIV reached 88.3% during the final year of the study period
      compared to only 3.9% at the beginning of the study period. Mortality was
      significantly higher among under-five children (p < 0.001) and those with HIV co
      infection (p < 0.001). On multivariate logistic regression, children 5-9 years
      [AOR = 2.50 (95% CI 1.67-3.74)] and 10-14 years [AOR = 2.70 (95% CI 1.86-3.91)]
      had a significantly higher successful treatment outcomes. On the other hand,
      smear positive PTB [AOR = 0.44 (95% CI 0.27-0.73), HIV co-infection (AOR =
      0.49(95% CI 0.30-0.80)] and unknown HIV sero-status [AOR = 0.60 (95% CI 0.42
      0.86)] were predictors of poor treatment outcomes. CONCLUSION: The proportion of
      childhood TB in this study is lower than the national estimate. The overall
      treatment success rate has met the WHO target. Nonetheless, younger children (< 5
      years), children with smear positive PTB and those with HIV co-infection need
      special attention to reduce poor treatment outcomes among children in the study
      area.

PMID- 24581268
TI  - The genetics of speciation: are complex incompatibilities easier to evolve?
AB  - Reproductive isolation can evolve readily when genotypes containing incompatible
      alleles are connected by chains of fit intermediates. Experimental crosses show
      that such Dobzhansky-Muller incompatibilities (DMIs) are often complex (involving
      alleles at three or more loci) and asymmetrical (such that reciprocal
      introgressions have very different effects on fitness). One possible explanation
      is that asymmetrical and complex DMIs are 'easier to evolve', because they block
      fewer of the possible evolutionary paths between the parental genotypes. To
      assess this argument, we model evolutionary divergence in allopatry and calculate
      the delays to divergence caused by DMIs of different kinds. We find that the
      number of paths is sometimes, though not always, a reliable predictor of the time
      to divergence. In particular, we find limited support for the idea that
      symmetrical DMIs take longer to evolve, but this applies largely to two-locus
      symmetrical DMIs (which leave no path of fit intermediates). Symmetrical complex
      DMIs can also delay divergence, but only in a limited region of parameter space.
      In most other cases, the presence and form of DMIs have little influence on times
      to divergence, and so we argue that ease of evolution is unlikely to be important
      in explaining the experimental data. 

PMID- 24581269
TI  - Endogenous endothelial progenitor cells participate in neovascularization via
      CXCR4/SDF-1 axis and improve outcome after stroke.
AB  - AIM: To study whether endogenous endothelial progenitor cells (EPCs) are involved
      in neovascularization after stroke. MATERIALS AND METHODS: Animal stroke models
      were established by subjecting male SD rats to permanent middle cerebral artery
      occlusion (pMCAO). Vessels in ischemic boundary zone (IBZ) were stained with
      antibody against laminin at 1 to 21 days after pMCAO. EPCs and newly formed
      vessels were identified by staining with special markers. After inhibiting
      recruitment of EPCs with AMD3100, a CXCR4 antagonist, endogenous EPCs, capillary
      density, cerebral blood flow (CBF) in IBZ, and neurobehavioral functions were
      assessed by staining, FITC-dextran, laser-Doppler perfusion monitor, and
      neurologic severity score. RESULTS: After pMCAO, vessels were found in IBZ at day
      3, reaching a peak at day 14. The change in number of laminin-positive cells
      showed a similar pattern with that of vessels. Apart from few endothelial cells,
      most of laminin-positive cells were endogenous EPCs. After treatment with
      AMD3100, the number of endogenous EPCs, capillary density, and CBF in IBZ were
      significantly reduced, and neurobehavioral functions were worse as compared with
      the normal saline group. CONCLUSIONS: Our findings suggested that endogenous EPCs
      participated in the neovascularization via CXCR4/SDF-1 axis after pMCAO and
      mobilizing endogenous EPCs could be a treatment alternative for stroke.

PMID- 24581270
TI  - Andrographolide inhibits HMGB1-induced inflammatory responses in human umbilical
      vein endothelial cells and in murine polymicrobial sepsis.
AB  - AIM: Nuclear DNA-binding protein high-mobility group box 1 (HMGB1) protein acts
      as a late mediator of severe vascular inflammatory conditions, such as septic
      shock, upregulating pro-inflammatory cytokines. Andrographolide (AG) is isolated
      from the plant of Andrographis paniculata and used as a folk medicine for
      treatment of viral infection, diarrhoea, dysentery and fever. However, the effect
      of AG on HMGB1-induced inflammatory response has not been studied. METHODS:
      Firstly, we accessed this question by monitoring the effects of post-treatment AG
      on lipopolysaccharide (LPS) and caecal ligation and puncture (CLP)-mediated
      release of HMGB1 and HMGB1-mediated regulation of pro-inflammatory responses in
      human umbilical vein endothelial cells (HUVECs) and septic mice. RESULTS: Post
      treatment AG was found to suppress LPS-mediated release of HMGB1 and HMGB1
      mediated cytoskeletal rearrangements. AG also inhibited HMGB1-mediated
      hyperpermeability and leucocyte migration in septic mice. In addition, AG
      inhibited production of tumour necrosis factor-alpha (TNF-alpha) and activation
      of AKT, nuclear factor-kappaB (NF-kappaB) and extracellular-regulated kinases
      (ERK) 1/2 by HMGB1 in HUVECs. AG also induced downregulation of CLP-induced
      release of HMGB1, production of interleukin (IL) 1beta/6/8 and mortality.
      CONCLUSION: Collectively, these results suggest that AG may be regarded as a
      candidate therapeutic agent for the treatment of vascular inflammatory diseases
      via inhibition of the HMGB1 signalling pathway.

PMID- 24581272
TI  - The relationship between cervical flexor endurance, cervical extensor endurance,
      VAS, and disability in subjects with neck pain.
AB  - BACKGROUND: Several tests have been suggested to assess the isometric endurance
      of the cervical flexor (NFME) and extensors (NEE) muscles. This study proposes to
      determine whether neck flexors endurance is related to extensor endurance, and
      whether cervical muscle endurance is related to disability, pain amount and pain
      stage in subjects with neck pain. METHODS: Thirty subjects (18 women, 12 men,
      mean +/- SD age: 43 +/- 12 years) complaining of neck pain filled out the Visual
      Analogue Scale (VAS) and the Neck Pain and Disability Scale-Italian version (NPDS
      I). They also completed the timed endurance tests for the cervical muscles.
      RESULTS: The mean endurance was 246.7 +/- 150 seconds for the NEE test, and 44.9
      +/- 25.3 seconds for the NMFE test. A significant correlation was found between
      the results of these two tests (r = 0.52, p = 0.003). A positive relationship was
      also found between VAS and NPDS-I (r = 0.549, p = 0.002). The endurance rates
      were similar for acute/subacute and chronic subjects, whereas males demonstrated
      significantly higher values compared to females in NFME test. CONCLUSIONS: These
      findings suggest that neck flexors and extensors endurance are correlated and
      that the cervical endurance is not significantly altered by the duration of
      symptoms in subjects with neck pain.

PMID- 24581273
TI  - Anophthalmia, hearing loss, abnormal pituitary development and response to growth
      hormone therapy in three children with microdeletions of 14q22q23.
AB  - BACKGROUND: Microdeletions of 14q22q23 have been associated with eye
      abnormalities and pituitary defects. Other phenotypic features in deletion
      carriers including hearing loss and response to growth hormone therapy are less
      well recognized. We studied genotype and phenotype of three newly identified
      children with 14q22q23 deletions, two girls and one boy with bilateral
      anophthalmia, and compared them with previously published deletion patients and
      individuals with intragenic defects in genes residing in the region. RESULTS: The
      three deletions were de novo and ranged in size between 5.8 and 8.9 Mb. All three
      children lacked one copy of the OTX2 gene and in one of them the deletion
      involved also the BMP4 gene. All three patients presented partial conductive
      hearing loss which tended to improve with age. Analysis of endocrine and growth
      phenotypes showed undetectable anterior pituitary, growth hormone deficiency and
      progressive growth retardation in all three patients. Growth hormone therapy led
      to partial catch-up growth in two of the three patients but just prevented
      further height loss in the third. CONCLUSIONS: The pituitary hypoplasia, growth
      hormone deficiency and growth retardation associated with 14q22q23 microdeletions
      are very remarkable, and the latter appears to have an atypical response to
      growth hormone therapy in some of the cases.

PMID- 24581271
TI  - A two years longitudinal study of a transgenic Huntington disease monkey.
AB  - BACKGROUND: A two-year longitudinal study composed of morphometric MRI measures
      and cognitive behavioral evaluation was performed on a transgenic Huntington's
      disease (HD) monkey. rHD1, a transgenic HD monkey expressing exon 1 of the human
      gene encoding huntingtin (HTT) with 29 CAG repeats regulated by a human
      polyubiquitin C promoter was used together with four age-matched wild-type
      control monkeys. This is the first study on a primate model of human HD based on
      longitudinal clinical measurements. RESULTS: Changes in striatal and hippocampal
      volumes in rHD1 were observed with progressive impairment in motor functions and
      cognitive decline, including deficits in learning stimulus-reward associations,
      recognition memory and spatial memory. The results demonstrate a progressive
      cognitive decline and morphometric changes in the striatum and hippocampus in a
      transgenic HD monkey. CONCLUSIONS: This is the first study on a primate model of
      human HD based on longitudinal clinical measurements. While this study is based a
      single HD monkey, an ongoing longitudinal study with additional HD monkeys will
      be important for the confirmation of our findings. A nonhuman primate model of HD
      could complement other animal models of HD to better understand the pathogenesis
      of HD and future development of diagnostics and therapeutics through longitudinal
      assessment.

PMID- 24581275
TI  - Diagnostic challenges in patients with bleeding phenotype and von Willebrand exon
      28 polymorphism p.D1472H.
AB  - Exon 28 polymorphism p.D1472H is associated with significantly lower von
      Willebrand Ristocetin cofactor activity (VWF:RCoF) to von Willebrand antigen
      (VWF:Ag) ratio compared to normal, but has been reported as not conferring
      haemorrhagic risk. The impact of this polymorphism while assessing symptomatic
      patients for von Willebrand disease (VWD) has not been previously analysed. We
      retrospectively reviewed charts of children with clinically significant bleeding
      and abnormal VW panel who underwent VW exon 28 analysis. Twenty-three of 63
      patients studied had p.D1472H. Of these 23 patients, 6 with borderline low
      VWF:RCo were given provisional diagnosis of VWD type 1 by treating physicians,
      which could be alternatively explained as due to the effect of p.D1472H. None of
      the patients with low VWF:RCo, decreased VWF:RCo/VWF:Ag ratio and p.D1472H had
      VWD type 2M mutations identified. This study illustrates the challenge in
      diagnosing VWD using ristocetin-based VW assay in symptomatic patients with
      p.D1472H. 

PMID- 24581274
TI  - Visualisation of time-varying respiratory system elastance in experimental ARDS
      animal models.
AB  - BACKGROUND: Patients with acute respiratory distress syndrome (ARDS) risk lung
      collapse, severely altering the breath-to-breath respiratory mechanics. Model
      based estimation of respiratory mechanics characterising patient-specific
      condition and response to treatment may be used to guide mechanical ventilation
      (MV). This study presents a model-based approach to monitor time-varying patient
      ventilator interaction to guide positive end expiratory pressure (PEEP)
      selection. METHODS: The single compartment lung model was extended to monitor
      dynamic time-varying respiratory system elastance, Edrs, within each breathing
      cycle. Two separate animal models were considered, each consisting of three fully
      sedated pure pietrain piglets (oleic acid ARDS and lavage ARDS). A staircase
      recruitment manoeuvre was performed on all six subjects after ARDS was induced.
      The Edrs was mapped across each breathing cycle for each subject. RESULTS: Six
      time-varying, breath-specific Edrs maps were generated, one for each subject.
      Each Edrs map shows the subject-specific response to mechanical ventilation (MV),
      indicating the need for a model-based approach to guide MV. This method of
      visualisation provides high resolution insight into the time-varying respiratory
      mechanics to aid clinical decision making. Using the Edrs maps, minimal time
      varying elastance was identified, which can be used to select optimal PEEP.
      CONCLUSIONS: Real-time continuous monitoring of in-breath mechanics provides
      further insight into lung physiology. Therefore, there is potential for this new
      monitoring method to aid clinicians in guiding MV treatment. These are the first
      such maps generated and they thus show unique results in high resolution. The
      model is limited to a constant respiratory resistance throughout inspiration
      which may not be valid in some cases. However, trends match clinical expectation
      and the results highlight both the subject-specificity of the model, as well as
      significant inter-subject variability.

PMID- 24581276
TI  - Improved real-world glycaemic outcomes with liraglutide versus other incretin
      based therapies in type 2 diabetes.
AB  - AIM: Liraglutide (LIRA) once-daily has provided greater A1C reductions than
      either exenatide (EXEN) twice-daily or sitagliptin (SITA) once-daily in head-to
      head trials. The objective of this analysis is to compare the real-world clinical
      effectiveness of these agents in the USA. METHODS: Using the IMS Health
      (Alexandria, VA, USA) integrated claims database, A1C outcomes in patients aged
      >= 18 years with type 2 diabetes (T2D) who initiated either LIRA, EXEN or SITA
      (including SITA/metformin) were retrospectively compared. Patients included in
      the analysis had >= 1 prescription for LIRA, EXEN or SITA between January and
      December 2010 (index period) and persisted with their index treatment regimens
      for 6 months post-index. Outcomes included changes in A1C from baseline (45 days
      pre-index through 7 days post-index) to follow-up [6 months post-index (+/- 45)]
      and the proportion of patients reaching A1C<7%. Multivariable regression models
      adjusted for confounding factors (e.g. age, comorbidities, baseline A1C and
      background antidiabetic therapy). RESULTS: The predicted change in A1C from
      baseline was greater for LIRA patients compared with both SITA (-1.08 vs. -0.68%;
      treatment difference 0.40%, p < 0.0001) and EXEN (-1.08 vs. -0.75%; treatment
      difference 0.32%, p < 0.001). Predicted A1C goal achievement, derived from the
      multivariate logistic regression model, was higher with LIRA compared with both
      SITA [64.4% (95% confidence interval, CI: 63.5-65.3) vs. 49.4% (95% CI: 48.5
      50.4); p < 0.0001] and EXEN [64.4% (95% CI: 63.5-65.3) vs. 53.6% (95% CI: 52.6
      54.6); p < 0.0001]. CONCLUSIONS: In clinical practice, LIRA was associated with
      significantly greater reductions in A1C and improved glycaemic goal attainment
      compared with either EXEN or SITA among adult patients with T2D.

PMID- 24581277
TI  - Indicator pathogens, organic matter and LAS detergent removal from wastewater by
      constructed subsurface wetlands.
AB  - BACKGROUND: Constructed wetland is one of the natural methods of municipal and
      industrial wastewater treatments with low initial costs for construction and
      operation as well as easy maintenance. The main objective of this study is to
      determine the values of indicator bacteria removal, organic matter, TSS, ammonia
      and nitrate affecting the wetland removal efficiency. RESULTS: The average
      concentration of E. coli and total coliform in the input is 1.127 * 1014 and 4.41
      * 1014 MPN/100 mL that reached 5.03 * 1012 and 1.13 * 1014 MPN/100 mL by reducing
      95.5% and 74.4% in wetland 2. Fecal streptococcus reached from the average 5.88 *
      1014 in raw wastewater to 9.69 * 1012 in the output of wetland 2. Wetland 2 could
      reduce 1.5 logarithmic units of E. coli. The removal efficiency of TSS for the
      wetlands is 68.87%, 71.4%, 57.3%, and 66% respectively. CONCLUSIONS: The overall
      results show that wetlands in which herbs were planted had a high removal
      efficiency about the indicator pathogens, organic matter, LAS detergent in
      comparison to a control wetland (without canes) and could improve physicochemical
      parameters (DO, ammonia, nitrate, electrical conductivity, and pH) of wastewater.

PMID- 24581279
TI  - In vivo synthesis of nanomaterials in plants: location of silver nanoparticles
      and plant metabolism.
AB  - Metallic nanoparticles (MeNPs) can be formed in living plants by reduction of the
      metal ions absorbed as soluble salts. It is very likely that plant metabolism has
      an important role in MeNP biosynthesis. The in vivo formation of silver
      nanoparticles (AgNPs) was observed in Brassica juncea, Festuca rubra and Medicago
      sativa. Plants were grown in Hoagland's solution for 30 days and then exposed for
      24 h to a solution of 1,000 ppm AgNO3. In the leaf extracts of control plants,
      the concentrations of glucose, fructose, ascorbic acid, citric acid and total
      polyphenols were determined. Total Ag content in plant fractions was determined
      by inductively coupled plasma atomic emission spectroscopy. Despite the short
      exposure time, the Ag uptake and translocation to plant leaves was very high,
      reaching 6,156 and 2,459 mg kg-1 in B. juncea and F. rubra, respectively.
      Ultrastructural analysis was performed by transmission electron microscopy (TEM),
      and AgNPs were detected by TEM X-ray microanalysis. TEM images of plant fractions
      showed the in vivo formation of AgNPs in the roots, stems and leaves of the
      plants. In the roots, AgNPs were present in the cortical parenchymal cells, on
      the cell wall of the xylem vessels and in regions corresponding to the pits. In
      leaf tissues, AgNPs of different sizes and shapes were located close to the cell
      wall, as well as in the cytoplasm and within chloroplasts. AgNPs were not
      observed in the phloem of the three plant species. This is the first report of
      AgNP synthesis in living plants of F. rubra. The contents of reducing sugars and
      antioxidant compounds, proposed as being involved in the biosynthesis of AgNPs,
      were quite different between the species, thus suggesting that it is unlikely
      that a single substance is responsible for this process. MSC 2010: 92 Biology and
      other natural sciences; 92Cxx Physiological, cellular and medical topics; 92C80
      Plant biology. 

PMID- 24581278
TI  - Clinicopathologic features of triple negative breast cancers: an experience from
      Pakistan.
AB  - BACKGROUND: Young age breast cancers are quite prevalent in our setup, a
      significant number of which exhibit triple negative phenotype. These cancers
      behave in an aggressive fashion and unresponsive to targeted adjuvant therapy. We
      aimed to evaluate clinical and histopathologic features of triple negative
      cancers in our population. METHODS: We retrospectively evaluated 1104 cases of
      primary breast cancers. Immunohistochemical studies for ER, PR and Her2neu
      followed by Her2neu gene amplification by FISH testing were done to identify 205
      (18.6%) cases of triple negative breast cancers. RESULTS: Mean age for triple
      negative breast cancer patients was 48.4 years (+/-12.3) and 60% of patients were
      diagnosed at less than 50 years of age. Although ductal carcinoma was the most
      frequent histologic type, a meaningful number of cases exhibited metaplastic and
      medullary like features (10.7% and 5.9% respectively). Similarly geographic
      necrosis involving more than 40% of tumor and extensive lymphocytic infiltration
      was a considerable finding. Mean Ki67 index was 45.2% (+/-25.2) and as a
      reflection of tumor grade, a significantly higher proportion of cases (66.3%)
      were under high risk Ki67 category (>30%). CONCLUSION: Triple negative breast
      cancers typify high grade breast cancers with a higher frequency of atypical
      medullary and metaplastic histologies. Their prevailing occurrence at a younger
      age raises question of under lying BRCA mutations in our population. Therefore,
      we suggest that risk factors including BRCA 1 mutations should be uncovered in
      reproductive age group breast cancers especially those disclosing basal like
      phenotype. VIRTUAL SLIDES: The virtual slide(s) for this article can be found
      here: http://www.diagnosticpathology.diagnomx.eu/vs/9042440621102239.

PMID- 24581281
TI  - Recruiting general practitioners for surveys: reflections on the difficulties and
      some lessons learned.
AB  - Surveys of GPs are essential to facilitate future planning and delivery of health
      services. However, recruitment of GPs into research has been disappointing with
      response rates declining over recent years. This study identified factors that
      facilitated or hampered GP recruitment in a recent survey of Australian GPs where
      a range of strategies were used to improve recruitment following poor initial
      responses. GP response rates for different stages of the survey were examined and
      compared with reasons GPs and leaders of university research networks cited for
      non-participation. Poor initial response rates were improved by including a
      questionnaire in the mail-out, changing the mail-out source from an unknown
      research team to locally known network leaders, approaching a group of GPs known
      to have research and training interests, and offering financial compensation.
      Response rates increased from below 1% for the first wave to 14.5% in the final
      wave. Using a known and trusted network of professionals to endorse the survey
      combined with an explicit compensation payment significantly enhanced GP response
      rates. To obtain response rates for surveys of GPs that are high enough to
      sustain external validity requires an approach that persuades GPs and their
      gatekeepers that it is worth their time to participate.

PMID- 24581283
TI  - An unusual presentation of probable dementia: rhyming, associations, and verbal
      disinhibition.
AB  - We report a case of probable Alzheimer's disease who presented with the unusual
      feature of disinhibited rhyming. Core language skills were largely intact but
      generative language was characterized by semantic-based associations, evident in
      tangential and associative content, and phonology-based associations, evident in
      rhyming, in the context of prominent executive dysfunction. We suggest this
      pattern is underpinned by a failure to terminate or inhibit verbal associations
      resulting in a 'loosening' of associations at the level of conceptual preparation
      for spoken language. 

PMID- 24581282
TI  - Analysis of the causes of spawning of large-scale, severe malarial epidemics and
      their rapid total extinction in western Provence, historically a highly endemic
      region of France (1745-1850).
AB  - BACKGROUND: The two main puzzles of this study are the onset and then sudden
      stopping of severe epidemics in western Provence (a highly malaria-endemic region
      of Mediterranean France) without any deliberate counter-measures and in the
      absence of significant population flux. METHODS: Malaria epidemics during the
      period from 1745 to 1850 were analysed against temperature and rainfall records
      and several other potentially relevant factors. RESULTS: Statistical analyses
      indicated that relatively high temperatures in early spring and in
      September/October, rainfall during the previous winter (principally December) and
      even from November to September and epidemics during the previous year could have
      played a decisive role in the emergence of these epidemics. Moreover, the
      epidemics were most likely not driven by other parameters (e.g., social,
      cultural, agricultural and geographical). Until 1776, very severe malarial
      epidemics affected large areas, whereas after this date, they were rarer and
      generally milder for local people and were due to canal digging activities. In
      the latter period, decreased rainfall in December, and more extreme and variable
      temperatures were observed. It is known that rainfall anomalies and temperature
      fluctuations may be detrimental to vector and parasite development. CONCLUSION:
      This study showed the particular characteristics of malaria in historical
      Provence. Contrary to the situation in most other Mediterranean areas, Plasmodium
      falciparum was most likely not involved (during the years with epidemics, the
      mean temperature during the months of July and August, among other factors, did
      not play a role) and the population had no protective mutation. The main parasite
      species was Plasmodium vivax, which was responsible for very severe diseases, but
      contrary to in northern Europe, it is likely that transmission occurred only
      during the period where outdoor sporogony was possible, and P. vivax sporogony
      was always feasible, even during colder summers. Possible key elements in the
      understanding of the course of malaria epidemics include changes in the virulence
      of P. vivax strains, the refractoriness of anophelines and/or the degree or
      efficiency of acquired immunity. This study could open new lines of investigation
      into the comprehension of the conditions of disappearance/emergence of severe
      malaria epidemics in highly endemic areas.

PMID- 24581285
TI  - Assortative mating based on cooperativeness and generosity.
AB  - Cooperative behaviour and generosity towards nonkin represent costly and risky
      behaviour that could be used as a signal of mate quality. Therefore, cooperative
      traits could serve as criteria in mate choice, leading to assortative mating for
      those traits. There is evidence of similarity in couples for altruistic traits.
      However, the literature is based on self-reports and does not provide conclusive
      proof of either a convergence across time or mating preferences. Here, we report
      a field experiment, conducted in rural villages in Senegal, showing that husbands
      and wives are similar with respect to their contributions to a public good and
      their charity donations. Further analyses suggest that this similarity is due to
      initial assortment rather than convergence of phenotypes. 

PMID- 24581284
TI  - Diverse arachnoid cyst morphology indicates different pathophysiological origins.
AB  - BACKGROUND: There are few, limited, and to some extent contradictory, reports on
      the cellular and subcellular morphology of arachnoid cysts. In the literature
      cyst membranes are described as similar to, or as vastly different from, normal
      arachnoid membranes. METHODS: This paper reports electron microscopic analyses of
      symptomatic cysts from 24 patients (12 males and 12 females; age 10-79), that
      underwent fenestration surgery. Fourteen cysts were located in the middle cranial
      fossa (temporal), one in the interpeduncular cistern, five in the posterior
      fossa, and four were overlying the frontal cortex. RESULTS: Microscopic findings
      confirmed the diverse nature of this clinical condition. Twelve cyst walls
      resembled normal arachnoid, four had a conspicuous core of dense fibrous tissue
      with a simple epithelial lining, and the remaining aberrant cysts exhibited non
      arachnoid luminal epithelia with plentiful microvilli and/or cilia, and also
      nervous tissue components in the wall. The possible identity and origin of
      various cyst types are discussed. We hypothesize that cysts are formed mostly at
      an early stage of embryonic development, as a teratological event. CONCLUSIONS:
      Cysts with various epithelial linings and extracellular components most likely
      have different barrier properties and fluid turnover characteristics. Further
      studies are needed to elucidate relations between cyst morphology, fluid
      composition, pathogenesis, and clinical behaviour including growth rate and
      relapse tendency.

PMID- 24581286
TI  - The accuracy of chromosomal microarray testing for identification of embryonic
      mosaicism in human blastocysts.
AB  - BACKGROUND: Most previous studies of chromosomal mosaicism in IVF embryos were
      performed by fluorescence in situ hybridization (FISH) methods. While there are
      reports implicating chromosome aneuploidy in implantation failure following
      transfer and pregnancy loss by spontaneous miscarriage, the significance of
      mosaicism for the developmental potential of growing embryos is unknown. However,
      the low prevalence of chromosomal mosaicism in chorionic villus sampling and
      amniotic fluid specimens suggests the presence of selection against mosaic
      embryos for implantation and early pregnancy. The absence of evidence for
      selective allocation of abnormal cells to the trophectoderm (TE) of mosaic
      blastocysts permits these cells to be a good proxy for embryonic mosaicism
      detection by chromosomal microarrays (CMA). The purpose of this study was to
      establish the limits of detection and the prevalence of chromosome mosaicism in
      day 5/6 human embryos using CMA with TE biopsies. RESULTS: From reconstitution
      experiments we established log2 ratio thresholds for mosaicism detection. These
      studies indicated that chromosomal mosaicism at levels as low as between 25-37%
      can be consistently identified. Follow-up studies by FISH on non-transferred
      abnormal embryos confirmed the diagnostic accuracy of CMA testing. The number of
      cells in a TE biopsy can influence mosaicism detection. CONCLUSIONS: Chromosomal
      microarrays can detect mosaicism in TE biopsies when present at levels as low as
      between 25-37% and the prevalence of day 5/6 blastocysts which were mosaic and
      had no other abnormalities reached 15% among a cohort of 551 embryos examined.
      Validated protocols for establishing detection thresholds for mosaicism are
      important to reduce the likelihood of transferring abnormal embryos.

PMID- 24581287
TI  - Evaluation of vertical forces in the pads of Pitbulls with cranial cruciate
      ligament rupture.
AB  - BACKGROUND: Cranial cruciate ligament rupture (CCLR) is one of the most important
      stifle injuries and a common cause of lameness in dogs. Our objective was to
      measure the vertical forces in the pads of Pitbulls with cranial cruciate
      ligament rupture (CCLR) using a pressure sensitive walkway. A pressure sensitive
      walkway was used to collect vertical force data from the pads of 10 Pitbulls
      affected with unilateral CCLR. Ten healthy Pitbulls were included in the study as
      controls. Velocity varied between 1.3 and 1.6 m/s and acceleration was kept below
      +/- 0.1 m/s2. Differences between groups and between pads in the same limb within
      groups were investigated using ANOVA and the Tukey test. The paired Student t
      test was employed to assess gait symmetry (p < 0.05). RESULTS: Peak vertical
      forces (PVF) were lower in the affected limb, particularly in the metatarsal pad.
      Increased PVF values in the forelimb and the contralateral hind limb pads of
      affected dogs suggest a compensatory effect. CONCLUSIONS: A consistent pattern of
      vertical force distribution was observed in the pads of dogs with CCLR. These
      data are important for increased understanding of vertical force distribution in
      the limb of dogs with CCLR disease. Kinetic analysis using pressure sensitive
      walkways can be useful in follow-up assessment of surgically treated dogs
      regardless of the surgical technique employed.

PMID- 24581288
TI  - When eating healthy is not healthy: orthorexia nervosa and its measurement with
      the ORTO-15 in Hungary.
AB  - BACKGROUND: For a better differential diagnosis of eating disorders, it is
      necessary to investigate their subtypes and develop specific assessment tools to
      measure their specific symptoms. Orthorexia nervosa is an alleged eating disorder
      in which the person is excessively preoccupied with healthy food. The ORTO-15,
      designed by Donini and colleagues, is the first and only at least partially
      validated instrument to measure this construct. The aims of the present study
      were to examine the psychometric properties of its Hungarian adaptation (ORTO-11
      Hu), and to investigate its relationship to food consumption and lifestyle habits
      in order to contribute to a better description of the phenomenon. METHODS: The
      ORTO-11-Hu, a lifestyle habits questionnaire, a food choice list indicating foods
      the participants choose to consume, and ten additional orthorexia-related
      questions were administered to a group of 810 Hungarian participants (89.4%
      female) aged between 20 and 70 (M = 32.39 +/- 10.37 years). RESULTS: Confirmatory
      factor analysis suggested a single factor structure for the 11-item shortened
      version of the instrument. Internal consistency of the measure was adequate
      (Cronbach's alpha = 0.82). No significant differences were found between males
      and females on the ORTO-11-Hu. Age and body mass index were significantly
      associated with a tendency towards orthorexia nervosa. Additional orthorexia
      related features were significantly correlated with ORTO-11-Hu scores: orthorexia
      nervosa tendency was associated not only with healthier food choices (eating more
      whole wheat cereals, less white wheat cereals, more fruit and vegetables) but
      with shopping in health food stores, as well as with some healthy lifestyle
      habits (more sports activity, specific dietary behaviors, and less alcohol
      intake). Individuals with higher orthorexia nervosa tendency also reported a
      greater tendency to advocate their healthy diet to their friends and family
      members. CONCLUSIONS: These results provide evidence for the reliability of ORTO
      11-Hu and some support for the construct validity of the instrument. The present
      study also contributes to the establishment of (diagnostic) criteria for this new
      subtype of eating disorders.

PMID- 24581291
TI  - Basic science, evidence, and clinical judgement.

PMID- 24581290
TI  - Current ideas to reduce or salvage radiation damage to salivary glands.
AB  - Radiation-induced hyposalivation is still a major problem after radiotherapy for
      head and neck cancer. Current and promising new thoughts to reduce or salvage
      radiation damage to salivary gland tissue are explored. The main cause underlying
      radiation-induced hyposalivation is a lack of functional saliva-producing acinar
      cells resulting from radiation-induced stem cell sterilization. Current methods
      to prevent that damage are radiation techniques to reduce radiation-injury to
      salivary gland tissue, surgical techniques to relocate salivary glands to a
      region receiving a lower cumulative radiation dose, and techniques to make
      salivary gland cells more resistant to radiation injury. These preventive
      techniques cannot be applied in all cases, also reduce tumor sensitivity, or do
      not result in a sufficient amelioration of the dryness-related complaints.
      Therefore, alternative methods on techniques to salvage salivary glands that are
      damaged by radiation are explored with promising results, such as stem cell
      therapies and gene transfer techniques to allow the radiation-injured salivary
      gland tissue to secrete water. 

PMID- 24581289
TI  - Genomic rearrangements and signatures of breeding in the allo-octoploid
      strawberry as revealed through an allele dose based SSR linkage map.
AB  - BACKGROUND: Breeders in the allo-octoploid strawberry currently make little use
      of molecular marker tools. As a first step of a QTL discovery project on fruit
      quality traits and resistance to soil-borne pathogens such as Phytophthora
      cactorum and Verticillium we built a genome-wide SSR linkage map for the cross
      Holiday x Korona. We used the previously published MADCE method to obtain full
      haplotype information for both of the parental cultivars, facilitating in-depth
      studies on their genomic organisation. RESULTS: The linkage map incorporates 508
      segregating loci and represents each of the 28 chromosome pairs of octoploid
      strawberry, spanning an estimated length of 2050 cM. The sub-genomes are denoted
      according to their sequence divergence from F. vesca as revealed by marker
      performance. The map revealed high overall synteny between the sub-genomes, but
      also revealed two large inversions on LG2C and LG2D, of which the latter was
      confirmed using a separate mapping population. We discovered interesting breeding
      features within the parental cultivars by in-depth analysis of our haplotype
      data. The linkage map-derived homozygosity level of Holiday was similar to the
      pedigree-derived inbreeding level (33% and 29%, respectively). For Korona we
      found that the observed homozygosity level was over three times higher than
      expected from the pedigree (13% versus 3.6%). This could indicate selection
      pressure on genes that have favourable effects in homozygous states. The level of
      kinship between Holiday and Korona derived from our linkage map was 2.5 times
      higher than the pedigree-derived value. This large difference could be evidence
      of selection pressure enacted by strawberry breeders towards specific haplotypes.
      CONCLUSION: The obtained SSR linkage map provides a good base for QTL discovery.
      It also provides the first biologically relevant basis for the discernment and
      notation of sub-genomes. For the first time, we revealed genomic rearrangements
      that were verified in a separate mapping population. We believe that haplotype
      information will become increasingly important in identifying marker-trait
      relationships and regions that are under selection pressure within breeding
      material. Our attempt at providing a biological basis for the discernment of sub
      genomes warrants follow-up studies to streamline the naming of the sub-genomes
      among different octoploid strawberry maps.

PMID- 24581292
TI  - Why do we continue to adopt medical practices based on pathophysiology alone when
      we should be insisting on clinical trials?

PMID- 24581293
TI  - Systematic review finds overlapping reviews were not mentioned in every other
      overview.
AB  - OBJECTIVES: The objective of this study was to determine if the authors mention
      overlapping reviews in overviews (reviews of reviews). In addition, we aimed to
      calculate the actual overlap in published overviews using newly introduced,
      validated measures. STUDY DESIGN AND SETTINGS: We systematically searched for
      overviews from 2009 to 2011. Reviews included in the overviews were obtained.
      Tables (review*primary publication) were generated for each overview. The first
      occurrence of a primary publication is defined as the index publication. We
      calculated the "corrected covered area" (CCA) as a measure of overlap by dividing
      the frequency of repeated occurrences of the index publication in other reviews
      by the product of index publications and reviews, reduced by the number of index
      publications. Subgroup analyses were performed to investigate further differences
      in the overviews. RESULTS: Only 32 of 60 overviews mentioned overlaps. The median
      CCA was 4.0. Validation of the CCA and other overlap measures was in accordance
      with our predefined hypotheses. The degree of overlap tended to be higher in
      health technology assessment reports than in journal publications and was higher
      with increasing numbers of publications. CONCLUSIONS: Overlaps must be reported
      in well-conducted overviews, and this can comprehensively be accomplished using
      the CCA method.

PMID- 24581294
TI  - Defining consensus: a systematic review recommends methodologic criteria for
      reporting of Delphi studies.
AB  - OBJECTIVE: To investigate how consensus is operationalized in Delphi studies and
      to explore the role of consensus in determining the results of these studies.
      STUDY DESIGN AND SETTINGS: Systematic review of a random sample of 100 English
      language Delphi studies, from two large multidisciplinary databases [ISI Web of
      Science (Thompson Reuters, New York, NY) and Scopus (Elsevier, Amsterdam, NL)],
      published between 2000 and 2009. RESULTS: About 98 of the Delphi studies
      purported to assess consensus, although a definition for consensus was only
      provided in 72 of the studies (64 a priori). The most common definition for
      consensus was percent agreement (25 studies), with 75% being the median threshold
      to define consensus. Although the authors concluded in 86 of the studies that
      consensus was achieved, consensus was only specified a priori (with a threshold
      value) in 42 of these studies. Achievement of consensus was related to the
      decision to stop the Delphi study in only 23 studies, with 70 studies terminating
      after a specified number of rounds. CONCLUSION: Although consensus generally is
      felt to be of primary importance to the Delphi process, definitions of consensus
      vary widely and are poorly reported. Improved criteria for reporting of methods
      of Delphi studies are required.

PMID- 24581295
TI  - The methodological quality of diagnostic test accuracy studies for
      musculoskeletal conditions can be improved.
AB  - OBJECTIVES: To provide an overview of reporting and methodological quality in
      diagnostic test accuracy (DTA) studies in the musculoskeletal field and evaluate
      the use of the QUality Assessment of Diagnostic Accuracy Studies (QUADAS)
      checklist. STUDY DESIGN AND SETTING: A literature review identified all
      systematic reviews that evaluated the accuracy of clinical tests to diagnose
      musculoskeletal conditions and used the QUADAS checklist. Two authors screened
      all identified reviews and extracted data on the target condition, index tests,
      reference standard, included studies, and QUADAS items. A descriptive analysis of
      the QUADAS checklist was performed, along with Rasch analysis to examine the
      construct validity and internal reliability. RESULTS: A total of 19 systematic
      reviews were included, which provided data on individual items of the QUADAS
      checklist for 392 DTA studies. In the musculoskeletal field, uninterpretable or
      intermediate test results are commonly not reported, with 175 (45%) studies
      scoring "no" to this item. The proportion of studies fulfilling certain items
      varied from 22% (item 11) to 91% (item 3). The interrater reliability of the
      QUADAS checklist was good and Rasch analysis showed excellent construct validity
      and internal consistency. CONCLUSION: This overview identified areas where the
      reporting and performance of diagnostic studies within the musculoskeletal field
      can be improved.

PMID- 24581296
TI  - The refinement of topics for systematic reviews: lessons and recommendations from
      the Effective Health Care Program.
AB  - OBJECTIVES: The Agency for Healthcare Research and Quality (AHRQ) Effective
      Health Care Program conducts systematic reviews of health-care topics nominated
      by stakeholders. Topics undergo refinement to ensure relevant questions of
      appropriate scope and useful reviews. Input from key informants, experts, and a
      literature scan informs changes in the nominated topic. AHRQ convened a work
      group to assess approaches and develop recommendations for topic refinement.
      STUDY DESIGN AND SETTING: Work group members experienced in topic refinement
      generated a list of questions and guiding principles relevant to the refinement
      process. They discussed each issue and reached agreement on recommendations.
      RESULTS: Topics should address important health-care questions or dilemmas,
      consider stakeholder priorities and values, reflect the state of the science, and
      be consistent with systematic review research methods. Guiding principles of
      topic refinement are fidelity to the nomination, relevance, research feasibility,
      responsiveness to stakeholder inputs, reduced investigator bias, transparency,
      and suitable scope. Suggestions for stakeholder engagement, synthesis of input,
      and reporting are discussed. Refinement decisions require judgment and balancing
      guiding principles. Variability in topics precludes a prescriptive approach.
      CONCLUSION: Accurate, rigorous, and useful systematic reviews require well
      refined topics. These guiding principles and methodological recommendations may
      help investigators refine topics for reviews.

PMID- 24581297
TI  - An original approach was used to better evaluate the capacity of a prognostic
      marker using published survival curves.
AB  - OBJECTIVES: Predicting chronic disease evolution from a prognostic marker is a
      key field of research in clinical epidemiology. However, the prognostic capacity
      of a marker is not systematically evaluated using the appropriate methodology. We
      proposed the use of simple equations to calculate time-dependent sensitivity and
      specificity based on published survival curves and other time-dependent
      indicators as predictive values, likelihood ratios, and posttest probability
      ratios to reappraise prognostic marker accuracy. STUDY DESIGN AND SETTING: The
      methodology is illustrated by back calculating time-dependent indicators from
      published articles presenting a marker as highly correlated with the time to
      event, concluding on the high prognostic capacity of the marker, and presenting
      the Kaplan-Meier survival curves. The tools necessary to run these direct and
      simple computations are available online at http://www.divat.fr/en/online
      calculators/evalbiom. RESULTS: Our examples illustrate that published conclusions
      about prognostic marker accuracy may be overoptimistic, thus giving potential for
      major mistakes in therapeutic decisions. CONCLUSION: Our approach should help
      readers better evaluate clinical articles reporting on prognostic markers. Time
      dependent sensitivity and specificity inform on the inherent prognostic capacity
      of a marker for a defined prognostic time. Time-dependent predictive values,
      likelihood ratios, and posttest probability ratios may additionally contribute to
      interpret the marker's prognostic capacity.

PMID- 24581298
TI  - A poor association was found between self-reported physical activity and
      estimated maximal oxygen uptake of sedentary multiethnic women.
AB  - OBJECTIVES: In health evaluations, physical activity (PA) and cardiorespiratory
      fitness (maximal oxygen uptake [VO2max]) are important variables. It is not
      always possible to assess both of them. If the association between self-reported
      PA and VO2max was strong, it would be possible to use the information on PA to
      make assumptions about VO2max and vice versa. However, little is known about this
      relation, in particular among women at high risk for cardiovascular disease. Our
      aim was to study the association between self-reported PA (Short QUestionnaire to
      ASses Health enhancing PA) and fitness (determined using the Siconolfi step test)
      among sedentary women in a multiethnic population. STUDY DESIGN AND SETTING:
      Participants were sampled from an exercise program for sedentary women (The
      Netherlands, 2008-09). Linear regression was performed with VO2max (dependent
      variable) and self-reported PA (independent variable); covariates were age and
      body mass index. RESULTS: One hundred ninety-seven women from different ethnic
      backgrounds were included. No significant association was found between VO2max
      and PA (R(2) = 0.60). CONCLUSION: A poor association was found between self
      reported PA and estimated VO2max. Hence, PA and VO2max represent two different
      aspects of health in sedentary women and cannot be used interchangeably. This
      should be taken into account when evaluating health promotion interventions or
      when making health risks statements in sedentary women in a multiethnic
      population.

PMID- 24581299
TI  - A charitable donation incentive did not increase physician survey response rates
      in a randomized trial.

PMID- 24581300
TI  - Development and validation of a health belief model based instrument for
      measuring factors influencing exercise behaviors to prevent osteoporosis in pre
      menopausal women (HOPE).
AB  - BACKGROUND: The health belief model (HBM) is the most commonly used conceptual
      framework for evaluating osteoporosis health belief and behaviors. The purpose of
      this study was to develop and evaluate the psychometric properties of a health
      belief model based questionnaire for exercise behavior for preventing
      osteoporosis among women aged 30 years and over. METHODS: This was a cross
      sectional study of a convenience sample of women aged 30 years and over in
      Tehran, Iran using a theory-based instrument (HOPE). The instrument contained 39
      items covering issues relate to osteoporosis prevention behavior. In this
      methodological study, exploratory and confirmatory factor analyses were used for
      psychometric evaluation. The Cronbach's alpha coefficient and Intraclass
      Correlation Coefficient (ICC) was used to evaluate the reliability of the scale.
      RESULTS: In all 240 women participated in the study. The mean age of participant
      was 39.2 +/- 7.8 years. The initial analysis extracted nine factors for the
      questionnaire that jointly accounted for 66.5% of variance observed. Confirmatory
      factor analysis showed that the data obtained was fit with Health Belief Model
      (HBM) and self-regulation construct (X2 = 1132.80, df = 629, P < 0.0001, CFI =
      0.94, GFI = 0.91, RMSEA = 0.05 and SRMR = 0.06). The Cronbach's alpha coefficient
      for the subscales ranged from 0.72 to 0.90 and Intraclass Correlation Coefficient
      (ICC) ranged from 0.71 to 0.98; well above acceptable thresholds. CONCLUSIONS:
      The HOPE was found to be appropriate instrument for measuring health belief and
      self-regulation for prevention of osteoporosis.

PMID- 24581302
TI  - [Triple-gene therapy in Parkinson disease (ProSavin): toward a putaminal dopamine
      factory?].

PMID- 24581301
TI  - Eribulin mesylate exerts specific gene expression changes in pericytes and
      shortens pericyte-driven capillary network in vitro.
AB  - BACKGROUND: Eribulin mesylate is a synthetic macrocyclic ketone analog of the
      marine sponge natural product halichondrin B. Eribulin is a tubulin-binding drug
      and approved in many countries worldwide for treatment of certain patients with
      advanced breast cancer. Here we investigated antiproliferative and antiangiogenic
      effects of eribulin on vascular cells, human umbilical vein endothelial cells
      (HUVECs) and human brain vascular pericytes (HBVPs), in vitro in comparison with
      another tubulin-binding drug, paclitaxel. METHODS: HUVECs and HBVPs were treated
      with either eribulin or paclitaxel and their antiproliferative effects were
      evaluated. Global gene expression profiling changes caused by drug treatments
      were studied using Affymetrix microarray platform and custom TaqMan Low Density
      Cards. To examine effects of the drugs on pericyte-driven in vitro angiogenesis,
      we compared lengths of capillary networks in co-cultures of HUVECs with HBVPs.
      RESULTS: Both eribulin and paclitaxel showed potent activities in in vitro
      proliferation of HUVECs and HBVPs, with the half-maximal inhibitory
      concentrations (IC50) in low- to sub-nmol/L concentrations. When gene expression
      changes were assessed in HUVECs, the majority of affected genes overlapped for
      both treatments (59%), while in HBVPs, altered gene signatures were drug
      dependent and the overlap was limited to just 12%. In HBVPs, eribulin selectively
      affected 11 pathways (p < 0.01) such as Cell Cycle Control of Chromosomal
      Replication. In contrast, paclitaxel was tended to regulate 27 pathways such as
      PI3K/AKT. Only 5 pathways were commonly affected by both treatments. In in vitro
      pericyte-driven angiogenesis model, paclitaxel showed limited activity while
      eribulin shortened the formed capillary networks of HUVECs driven by HBVPs at low
      nmol/L concentrations starting at day 3 after treatments. CONCLUSIONS: Our
      findings suggest that pericytes, but not endothelial cells, responded
      differently, to two mechanistically-distinct tubulin-binding drugs, eribulin and
      paclitaxel. While eribulin and paclitaxel induced similar changes in gene
      expression in endothelial cells, in pericytes their altered gene expression was
      unique and drug-specific. In the functional endothelial-pericyte co-culture
      assay, eribulin, but not paclitaxel showed strong efficacy not only as a
      cytotoxic drug but also as a potent antivascular agent that affected pericyte
      driven in vitro angiogenesis.

PMID- 24581303
TI  - Unravelling the effects of contemporary and historical range expansion on the
      distribution of genetic diversity in the damselfly Coenagrion scitulum.
AB  - Although genetic diversity provides the basic substrate for evolution, there are
      a limited number of studies that assess the impact of recent climate change on
      intraspecific genetic variation. This study aims to unravel the degree to which
      historical and contemporary factors shape genetic diversity and structure across
      a large part of the range of the range-expanding damselfly Coenagrion scitulum
      (Rambur, 1842). A total of 525 individuals from 31 populations were genotyped at
      nine microsatellites, and a subset was sequenced at two mitochondrial genes. We
      inferred the importance of geography, environmental factors, and recent range
      expansion on genetic diversity and structure. Genetic diversity decreased going
      westwards, suggesting a signature of historical post-glacial expansion from east
      to west and the presence of eastern refugia. Although genetic differentiation
      decreased going northwards, it increased in the northern edge populations,
      suggesting a role of contemporary range expansion on the genetic make-up of
      populations. The phylogeographical context was proven to be essential in
      understanding and identifying the genetic signatures of local contemporary
      processes. Within this framework, our results highlight that recent range
      expansion of a good disperser can decrease genetic diversity and increase genetic
      differentiation which should be considered when devising suitable conservation
      strategies. 

PMID- 24581304
TI  - British HIV Association guidelines for the management of hepatitis viruses in
      adults infected with HIV 2013.

PMID- 24581305
TI  - Pulsed laser-induced formation of silica nanogrids.
AB  - Silica grids with micron to sub-micron mesh sizes and wire diameters of 50 nm are
      fabricated on fused silica substrates. They are formed by single-pulse structured
      excimer laser irradiation of a UV-absorbing silicon suboxide (SiOx) coating
      through the transparent substrate. A polydimethylsiloxane (PDMS) superstrate
      (cover layer) coated on top of the SiOx film prior to laser exposure serves as
      confinement for controlled laser-induced structure formation. At sufficiently
      high laser fluence, this process leads to grids consisting of a periodic loop
      network connected to the substrate at regular positions. By an additional high
      temperature annealing, the residual SiOx is oxidized, and a pure SiO2 grid is
      obtained. PACS: 81.07.-b; 81.07.Gf; 81.65.Cf.

PMID- 24581306
TI  - Risk estimation using probability machines.
AB  - BACKGROUND: Logistic regression has been the de facto, and often the only, model
      used in the description and analysis of relationships between a binary outcome
      and observed features. It is widely used to obtain the conditional probabilities
      of the outcome given predictors, as well as predictor effect size estimates using
      conditional odds ratios. RESULTS: We show how statistical learning machines for
      binary outcomes, provably consistent for the nonparametric regression problem,
      can be used to provide both consistent conditional probability estimation and
      conditional effect size estimates. Effect size estimates from learning machines
      leverage our understanding of counterfactual arguments central to the
      interpretation of such estimates. We show that, if the data generating model is
      logistic, we can recover accurate probability predictions and effect size
      estimates with nearly the same efficiency as a correct logistic model, both for
      main effects and interactions. We also propose a method using learning machines
      to scan for possible interaction effects quickly and efficiently. Simulations
      using random forest probability machines are presented. CONCLUSIONS: The models
      we propose make no assumptions about the data structure, and capture the patterns
      in the data by just specifying the predictors involved and not any particular
      model structure. So they do not run the same risks of model mis-specification and
      the resultant estimation biases as a logistic model. This methodology, which we
      call a "risk machine", will share properties from the statistical machine that it
      is derived from.

PMID- 24581307
TI  - Bioremediation of p-Nitrophenol by Pseudomonas putida 1274 strain.
AB  - BACKGROUND: p-Nitrophenol (PNP) occurs as contaminants of industrial effluents
      and it is the most important environmental pollutant and causes significant
      health and environmental risks, because it is toxic to many living organisms.
      Nevertheless, the information regarding PNP degradation pathways and their
      enzymes remain limited. OBJECTIVE: To evaluate the efficacy of the Pseudomonas
      Putida 1274 for removal of PNP. METHODS: P. putida MTCC 1274 was obtained from
      MTCC Chandigarh, India and cultured in the minimal medium in the presence of PNP.
      PNP degradation efficiency was compared under different pH and temperature
      ranges. The degraded product was isolated and analyzed with different
      chromatographic and spectroscopic techniques. RESULTS: P. putida 1274 shows good
      growth and PNP degradation at 37 degrees C in neutral pH. Acidic and alkali pH
      retarded the growth of P. putida as well as the PNP degradation. On the basis of
      specialized techniques, hydroquinone was identified as major degraded product.
      The pathway was identified for the biodegradation of PNP. It involved initial
      removal of the nitrate group and formation of hydroquinone as one of the
      intermediates. CONCLUSION: Our results suggested that P. putida 1274 strain would
      be a suitable aspirant for bioremediation of nitro-aromatic compounds
      contaminated sites in the environment.

PMID- 24581308
TI  - Plasmodium vivax and Plasmodium falciparum ex vivo susceptibility to anti
      malarials and gene characterization in Rondonia, West Amazon, Brazil.
AB  - BACKGROUND: Chloroquine (CQ), a cost effective antimalarial drug with a
      relatively good safety profile and therapeutic index, is no longer used by itself
      to treat patients with Plasmodium falciparum due to CQ-resistant strains. P.
      vivax, representing over 90% of malaria cases in Brazil, despite reported
      resistance, is treated with CQ as well as with primaquine to block malaria
      transmission and avoid late P. vivax malaria relapses. Resistance to CQ and other
      antimalarial drugs influences malaria control, thus monitoring resistance
      phenotype by parasite genotyping is helpful in endemic areas. METHODS: A total of
      47 P. vivax and nine P. falciparum fresh isolates were genetically characterized
      and tested for CQ, mefloquine (MQ) and artesunate (ART) susceptibility in vitro.
      The genes mdr1 and pfcrt, likely related to CQ resistance, were analyzed in all
      isolates. Drug susceptibility was determined using short-term parasite cultures
      of ring stages for 48 to 72 hour and thick blood smears counts. Each parasite
      isolate was tested with the antimalarials to measure the geometric mean of 50%
      inhibitory concentration. RESULTS: The low numbers of  P. falciparum isolates
      reflect the species prevalence in Brazil; most displayed low sensitivity to CQ
      (IC50 70 nM). However, CQ resistance was rare among P. vivax isolates (IC50 of 32
      nM). The majority of P. vivax and P. falciparum isolates were sensitive to ART
      and MQ. One hundred percent of P. falciparum isolates carried non-synonymous
      mutations in the pfmdr1 gene in codons 184, 1042 and 1246, 84% in codons 1034 and
      none in codon 86, a well-known resistance mutation. For the pfcrt gene, mutations
      were observed in codons 72 and 76 in all P. falciparum isolates. One P.
      falciparum isolate from Angola, Africa, showing sensitivity to the antimalarials,
      presented no mutations. In P. vivax, mutations of pvmdr1 and the multidrug
      resistance gene 1 marker at codon F976 were absent. CONCLUSION: All P. falciparum
      Brazilian isolates showed CQ resistance and presented non-synonymous mutations in
      pfmdr1 and pfcrt. CQ resistant genotypes were not present among P. vivax isolates
      and the IC50 values were low in all samples of the Brazilian West Amazon.

PMID- 24581309
TI  - Understanding psychological distress among mothers in rural Nepal: a qualitative
      grounded theory exploration.
AB  - BACKGROUND: There is a large burden of psychological distress in low and middle
      income countries, and culturally relevant interventions must be developed to
      address it. This requires an understanding of how distress is experienced. We
      conducted a qualitative grounded theory study to understand how mothers
      experience and manage distress in Dhanusha, a low-resource setting in rural
      Nepal. We also explored how distressed mothers interact with their families and
      the wider community. METHODS: Participants were identified during a cluster
      randomised controlled trial in which mothers were screened for psychological
      distress using the 12-item General Health Questionnaire (GHQ-12). We conducted 22
      semi-structured interviews with distressed mothers (GHQ-12 score >= 5) and one
      with a traditional healer (dhami), as well as 12 focus group discussions with
      community members. Data were analysed using grounded theory methods and a model
      was developed to explain psychological distress in this setting. RESULTS: We
      found that distress was termed tension by participants and mainly described in
      terms of physical symptoms. Key perceived causes of distress were poor health,
      lack of sons, and fertility problems. Tension developed in a context of limited
      autonomy for women and perceived duty towards the family. Distressed mothers
      discussed several strategies to alleviate tension, including seeking treatment
      for perceived physical health problems and tension from doctors or dhamis, having
      repeated pregnancies until a son was delivered, manipulating social circumstances
      in the household, and deciding to accept their fate. Their ability to implement
      these strategies depended on whether they were able to negotiate with their in
      laws or husbands for resources. CONCLUSIONS: Vulnerability, as a consequence of
      gender and social disadvantage, manifests as psychological distress among mothers
      in Dhanusha. Screening tools incorporating physical symptoms of tension should be
      envisaged, along with interventions to address gender inequity, support marital
      relationships, and improve access to perinatal healthcare.

PMID- 24581310
TI  - When higher doses in opioid replacement treatment are still inadequate -
      association to multidimensional illness severity: a cohort study.
AB  - BACKGROUND: Opioid replacement treatment (ORT) with methadone is regarded as gold
      standard in the treatment of opioid addiction. Treatment doses of 60 mg methadone
      per day and above are associated with better treatment retention and reduction in
      the use of heroin and cocaine. However, an absolute dose level cannot function as
      parameter for adequate dosing. This study aims to determine dose adequacy in a
      sample of patients on stable methadone treatment, and to relate dose adequacy to
      disease severity. METHODS: This study was designed as open prospective cohort
      study over 12 months, with baseline data reported here. Patients on stable
      substitution treatment with methadone (Eptadone(r)) were consecutively included.
      Medical and socio-demographic data were gathered and the instruments Opiate
      Dosage Adequacy Scale (ODAS), European Addiction Severity Index (EuropASI) and
      the Derogatis Interview for Sexual Functioning - Self Report (DISF-SR) were
      applied. RESULTS: Five hundred and sixteen subjects, who received on average 60.3
      (+/-30.4) mg methadone per day, were included. According to ODAS, 40.6% suffered
      from an inadequate dosing, and 59.4% had an adequate dose. Patients with an
      adequate dose received on average 57.8 (+/-27.5) mg methadone per day, whilst
      patients with an inadequate dose received on average 70.6 (+/-33.0) mg per day.
      The frequencies of patients with methadone doses of less than 60 mg per were
      45.4% in the inadequate and 60.6% in the adequate group. The inadequate group
      suffered from a statistically significant higher burden of addiction related
      problems in all EuropASI domains. Sexual functioning did not differ by adequacy
      group, but women suffered from more pronounced sexual dysfunction as compared to
      men. CONCLUSION: A high frequency of inadequate dosing was found in this sample
      of patients on ORT. Higher disease severity should alert for possible need of
      even higher methadone doses. The tendency to low methadone doses warrants further
      research in the treatment system. Higher methadone doses are not related to
      increased sexual dysfunction. Sexual dysfunction, especially in women, should be
      considered in treatment.

PMID- 24581311
TI  - Safety and effectiveness of large gel particle hyaluronic acid with lidocaine for
      correction of midface volume loss.
AB  - BACKGROUND: Midface volume loss and contour deficiency are often treated using
      soft-tissue fillers capable of elevating and supporting facial features.
      OBJECTIVE: To evaluate the effectiveness and safety of large gel particle
      hyaluronic acid with 0.3% lidocaine (LGP-HA-L) for the treatment of midface
      volume loss or contour deficiency. METHODS AND MATERIALS: This 24-week, open
      label study recruited adults aged 18 to 65 with bilateral moderate to substantial
      midface volume loss or contour deficiency (Medicis Midface Volume Scale (MMVS)
      score 3-4). The primary effectiveness measure was MMVS response (>=1-grade
      improvement) 8 weeks after treatment according to evaluators blinded to injection
      volume. RESULTS: All enrolled patients (n = 40; 85.0% female; mean +/- SD age
      53.1 +/- 7.0 years) completed the study. Mean +/- SD injected volume for both
      sides of the midface was 5.3 +/- 2.5 mL. Week 8 MMVS response rates were 97.5%
      according to blinded evaluators and treating investigators and 90.0% according to
      patients; week 24 rates were 90.0%, 92.5%, and 82.5%, respectively. Global
      Aesthetic Improvement Scale response rates were 95.0% to 100.0% throughout the
      study. Adverse events were reported in 60.0% of patients and were mild or
      moderate; all resolved by study end and most within 1 week. CONCLUSION: Midface
      volume loss or contour deficiency may be safely and effectively corrected using
      LGP-HA-L.

PMID- 24581312
TI  - Commentary: Comparison of outcomes for malignant melanoma of the face treated
      with Mohs micrographic surgery and wide local excision.

PMID- 24581314
TI  - Commentary: Mohs micrographic surgery concordance between Mohs surgeons and
      dermatopathologists.

PMID- 24581313
TI  - Mohs micrographic surgery concordance between Mohs surgeons and
      dermatopathologists.
AB  - BACKGROUND: Mohs micrographic surgery (MMS) is the preferred treatment modality
      for high-risk nonmelanoma skin cancer because of the high cure rates and tissue
      sparing effect. Its outcome is highly dependent on the expertise and accuracy of
      the Mohs surgeon in the interpretation of frozen sections. OBJECTIVE: This
      retrospective study evaluated the level of concordance between Mohs surgeons and
      dermatopathologists in reading histology slides from MMS procedures. METHODS AND
      MATERIALS: A Mohs surgeon read 170 randomly selected slides for a quality
      assurance audit during excision, and then a dermatopathologist blindly read them
      at a separate time. Absence or presence of tumour and the final diagnosis were
      recorded on a standardized form. RESULTS: An overall concordance of 99.4% was
      demonstrated. True discordance was recorded in only one of 170 cases.
      Intraepidermal atypia was the most challenging scenario for Mohs surgeons.
      CONCLUSIONS: The high rate of agreement in this study confirms that adequately
      trained MMS surgeons have sufficient expertise and training for accurate and
      precise frozen sections interpretation.

PMID- 24581315
TI  - The racket graft.

PMID- 24581316
TI  - Trichorrhexis nodosa after hair transplantation: dermoscopic, pathologic and
      electron microscopy analyses.

PMID- 24581317
TI  - Commentary: Pseudocystic encapsulation: a late noninflammatory complication of
      hyaluronic acid filler injections.

PMID- 24581318
TI  - The influence of the direction of J-tip on the placement of a subclavian
      catheter: real time ultrasound-guided cannulation versus landmark method, a
      randomized controlled trial.
AB  - BACKGROUND: It has been reported that the direction of the guidewire J-tip is
      associated with misplacement of a central venous catheter. We hypothesized that
      real-time ultrasound-guided infraclavicular subclavian venous cannulation would
      be less influenced by the direction of guidewire J-tip compared to landmark
      method. METHODS: Sixty adult patients who required subclavian venous
      catheterization for neurosurgery were enrolled in this prospective randomized
      controlled study. Patients were randomly divided into a landmark group (n = 30)
      or an ultrasound group (n = 30). After the subclavian vein was punctured, the
      guidewire was advanced with the guidewire J-tip directed cephalad. Misplacement
      or advancement failure of the guidewire was regarded as an unsuccessful
      placement. Postoperative chest radiography was performed to confirm pneumothorax
      and the location of the catheter tip. RESULTS: The two groups were comparable
      with respect to age, gender, height, and weight distribution. The incidence of
      unsuccessful guidewire placement was lower in the ultrasound group than in the
      landmark group (13% vs. 47%, P = 0.01). Among the unsuccessful guidewire
      placements, the incidence of misplacement were comparable between the groups and
      were all located in the ipsilateral internal jugular vein (7% vs. 7%). However,
      the incidence of advancement failure was significantly higher in landmark group
      (40% vs. 7%, P = 0.005). There were no complications such as pneumothorax or
      hemothorax. CONCLUSIONS: The proper placement of guidewire was less influenced by
      the direction of the guidewire J-tip with ultrasound-guided subclavian venous
      cannulation than with the landmark approach.

PMID- 24581319
TI  - Language, culture, and task shifting--an emerging challenge for global mental
      health.
AB  - Language is at the heart of mental health care. Many high-income countries have
      sophisticated interpreter services, but in low- and middle-income countries there
      are not sufficient professional services, let alone interpreter services, and
      task shifting is used. In this article, we discuss this neglected issue in the
      context of low- and middle-income countries, where task shifting has been
      suggested as a solution to the problem of scarce mental health resources. The
      large diversity of languages in low- and middle-income countries, exacerbated by
      wide-scale migration, has implications for the scale-up of services. We suggest
      that it would be useful for those who are working innovatively to develop locally
      delivered mental health programmes in low- and middle-income countries to explore
      and report on issues of language and how these have been addressed. We need to
      know more about local challenges, but also about local solutions which seem to
      work, and for this we need more information from the field than is currently
      available. 

PMID- 24581320
TI  - Periodontal disease in Thai patients with rheumatoid arthritis.
AB  - AIM: To evaluate the prevalence and severity of periodontal disease in patients
      with rheumatoid arthritis (RA) who attended a rheumatology clinic in a university
      hospital. METHODS: All consecutive patients with RA who attended the rheumatology
      clinic between June 2009 and January 2010 were asked to enroll in this study. All
      participants answered questionnaires, which included demographic data, medical
      history, medications used and smoking habits. A full mouth periodontal
      examination, including gingival index, plaque index, probing pocket depth and
      clinical attachment level was performed. Only cases that had at least 20 teeth
      were included in this study. Rheumatoid arthritis parameters, including number of
      tender and swollen joints, erythrocyte sedimentation rate, the presence of
      rheumatoid factor (RF), hand radiographs, Disease Activity Index (DAS) and health
      status using the Thai Health Assessment Questionnaire (HAQ), were determined. The
      association between RA parameters and periodontal condition was examined.
      RESULTS: There were 196 participants (87.2% female) with a mean age of 51.7 +/-
      9.70 years, mean disease duration of 9.62 +/- 7.0 years and mean DAS score of
      4.64 +/- 1.25. Eighty-two per cent were RF-positive. Moderate and severe
      periodontitis were found in 42% and 57%, respectively. Higher age, male gender,
      previous or current smoking and high level of plaque score were associated with
      severe periodontal disease. No differences in RA parameters were found between
      groups of patients who had moderate and severe periodontitis. CONCLUSIONS: We
      found a high prevalence of periodontitis in Thai patients with RA. However, there
      was no association between RA parameters and periodontal conditions.

PMID- 24581321
TI  - Description and design considerations of a randomized clinical trial
      investigating the effect of a multidisciplinary cognitive-behavioural
      intervention for patients undergoing lumbar spinal fusion surgery.
AB  - BACKGROUND: The ideal rehabilitation strategy following lumbar spinal fusion
      surgery has not yet been established. This paper is a study protocol, describing
      the rationale behind and the details of a cognitive-behavioural rehabilitation
      intervention for lumbar spinal fusion patients based on the best available
      evidence. Predictors of poor outcome following spine surgery have been identified
      to provide targets for the intervention, and the components of the intervention
      were structured in accordance with the cognitive-behavioural model. The study
      aims to compare the clinical and economical effectiveness of a cognitive
      behavioural rehabilitation strategy to that of usual care for patients undergoing
      lumbar spinal fusion surgery. METHODS/DESIGN: The study is a randomized clinical
      trial including 96 patients scheduled for lumbar spinal fusion surgery due to
      degenerative disease or spondylolisthesis. Patients were recruited in the period
      October 2011 to July 2013, and the follow-up period is one year from date of
      surgery. Patients are allocated on a 1:2 ratio (control: intervention) to either
      treatment as usual (control group), which implies surgery and the standard
      postoperative rehabilitation, or in addition to this, a patient education
      focusing on pain behaviour and pain coping (intervention group). It takes place
      in a hospital setting, and consists of six group-based sessions, managed by a
      multidisciplinary team of health professionals.The primary outcomes are
      disability (Oswestry Disability Index) and sick leave, while secondary outcomes
      include coping (Coping Strategies Questionnaire), fear-avoidance belief (Fear
      Avoidance Belief Questionnaire), pain (Low Back Pain Rating Scale, pain index),
      mobility during hospitalization (Cumulated Ambulation Score), generic health
      related quality of life (EQ-5D) and resource use. Outcomes are measured using
      self report questionnaires, medical records and national registers. DISCUSSION:
      It is expected that the intervention can provide better functional outcome, less
      pain and earlier return to work after lumbar spinal fusion surgery. By combining
      knowledge and evidence from different knowledge areas, the project aims to
      provide new knowledge that can create greater consistency in patient treatment.
      We expect that the results can make a significant contribution to development of
      guidelines for good rehabilitation of patients undergoing lumbar spinal fusion.
      TRIAL REGISTRATION: Current Controlled Trials ISRCTN42281022.

PMID- 24581322
TI  - A blinded, randomized, placebo-controlled trial of the efficacy and safety of the
      Janus kinase inhibitor oclacitinib (Apoquel(r)) in client-owned dogs with atopic
      dermatitis.
AB  - BACKGROUND: Pruritus is the hallmark clinical sign of atopic dermatitis (AD) in
      dogs. Preliminary study results suggest that oclacitinib, a selective Janus
      kinase inhibitor, could reduce pruritus and associated inflammatory skin lesions
      in dogs with AD. HYPOTHESIS/OBJECTIVES: The objective was to evaluate efficacy
      and safety of oclacitinib (Apoquel(r)) for the control of AD in a randomized,
      double-blind, placebo-controlled trial. ANIMALS: Clinicians at 18 specialty
      clinics enrolled client-owned dogs (n = 299) with a history of chronic AD.
      METHODS: Dogs were randomized to receive either oclacitinib (0.4-0.6 mg/kg twice
      daily for 14 days and then once daily for up to 112 days) or an excipient-matched
      placebo. Owners assessed visual analog scale (VAS) scores of pruritus on days 0,
      1, 2, 7, 14, 28, 56, 84 and 112. Clinicians assessed Canine AD Extent and
      Severity Index (CADESI-02) scores on days 0, 14, 28, 56, 84 and 112. RESULTS: On
      days 1, 2, 7, 14 and 28, oclacitinib-treated dogs had a 29.5, 42.3, 61.5, 66.7
      and 47.4% reduction from baseline in owner-assessed pruritus scores,
      respectively, compared with a 6.5, 9.1, 6.5, 3.9 and 10.4% reduction in placebo
      treated dogs. On days 14 and 28, dermatologists recorded a 48.4% reduction in
      CADESI-02 scores in oclacitinib-treated dogs compared with a 1.7% reduction and a
      3.6% increase in placebo-treated dogs. After day 28, >86% of all placebo-treated
      dogs had moved to an open-label study, making between-group comparisons biased.
      Differences were significant at all time points assessed (P < 0.0001).
      CONCLUSIONS AND CLINICAL IMPORTANCE: Oclacitinib provided rapid, effective and
      safe control of AD, with substantial improvement in VAS and CADESI-02 scores.

PMID- 24581323
TI  - Effect of the vascular endothelial growth factor expression level on angiopoietin
      2-mediated nasopharyngeal carcinoma growth.
AB  - BACKGROUND: The overexpression of angiopoietin-2 (Ang-2) has both pro-tumorigenic
      and anti-tumorigenic effects. However, the mechanisms of this protein's dual
      effects are poorly understood, and it remains unclear how Ang-2 cooperates with
      vascular endothelial growth factor (VEGF). In the current study, we investigated
      the effects of Ang-2 overexpression on nasopharyngeal carcinoma growth in the
      presence of different levels of VEGF. METHODS: Ang-2 was introduced into the CNE2
      cell line by liposome transfection, and the expression of endogenous VEGF was
      inhibited by microRNA-mediated RNA interference. CNE2 cells expressing varying
      levels of Ang-2 and VEGF were injected subcutaneously into the flanks of nude
      mice. Tumor growth was measured, and vessels from the harvested tumors were
      analyzed. RESULTS: The overexpression of Ang-2 had no obvious effect on CNE2
      tumor growth in the presence of endogenous VEGF but significantly inhibited CNE2
      tumor growth when the expression of endogenous VEGF was silenced, and the Ang
      2/VEGF ratio is negatively correlated with tumor growth. Ang-2 overexpression
      decreased the percentage of alpha-SMA-positive cells around the tumor vessels but
      reduced the microvessel density only in the absence of VEGF. CONCLUSIONS: Our
      results indicate that the effects of Ang-2 on nasopharyngeal carcinoma are highly
      dependent on the level of VEGF expression, Ang-2/VEGF ratio may offer a novel
      therapeutic approach for treating human cancer.

PMID- 24581324
TI  - Unplanned antiretroviral treatment interruptions, genetic barrier, and
      development of resistance.

PMID- 24581325
TI  - PEPSE and coke: should we be increasing awareness of HIV post-exposure
      prophylaxis for consensual risk exposures?

PMID- 24581326
TI  - Reported municipal costs from outdoor smoke-free by-laws-experience from Ontario,
      Canada.
AB  - BACKGROUND: In 2006, enclosed public and workplaces in Ontario were made smoke
      free by the Smoke-free Ontario Act (SFOA). Numerous area municipalities across
      the province have since developed local by-laws that are more restrictive than
      the SFOA and ban smoking in outdoor environments including parks, beaches, and
      patios. The current study measured reported costs associated with the
      implementation and enforcement of smoke-free outdoor municipal by-laws including
      materials and staffing costs. The study also assessed the number of warnings or
      tickets issued to smokers. Ontario communities with a by-law in force for at
      least 2 years were included in the sample (n = 42). The study was completed by
      88% of area municipalities (n = 37). Municipal staff and managers completed a
      survey by telephone between June-September 2012. FINDINGS: No area municipality
      surveyed reported that they hired additional enforcement staff as a result of
      their community's smoke-free by-law. Most municipalities (95%) posted signage to
      support awareness of their by-law; signs costs ranged from $40-$150/sign with
      most municipalities reporting signs were made in-house. Most communities reported
      actively enforcing the by-law; six communities reported they had issued tickets
      to people not in compliance with outdoor smoking restrictions. CONCLUSIONS: The
      implementation, promotion, and enforcement of outdoor smoke-free by-laws have
      required municipal staff time and in most cases have promotional costs, but these
      have come from existing budgets and using existing staff. Outdoor smoke-free by
      laws have not created significant burdens on municipal enforcement staff or on
      municipal budgets.

PMID- 24581327
TI  - Popliteal cysts and subgastrocnemius bursitis are associated with knee symptoms
      and structural abnormalities in older adults: a cross-sectional study.
AB  - INTRODUCTION: The role of popliteal cysts and subgastrocnemius bursitis in knee
      joint homeostasis is uncertain. The aim of this study is to describe cross
      sectional associations between popliteal cysts, subgastrocnemius bursitis, knee
      symptoms and structural abnormalities in older adults. METHODS: A cross-sectional
      sample of 900 randomly-selected subjects (mean age 63 years, 48% female) were
      studied. Knee pain, stiffness and dysfunction were assessed by self-administered
      Western Ontario McMaster Osteoarthritis Index (WOMAC) questionnaire. Radiographic
      knee osteophyte and joint space narrowing (JSN) were recorded. Magnetic resonance
      imaging (MRI) was utilized to assess popliteal cysts, subgastrocnemius bursitis,
      cartilage defects and bone marrow lesions (BMLs). RESULTS: Popliteal cysts were
      present in 11.7% and subgastrocnemius bursitis in 12.7% of subjects.
      Subgastrocnemius bursitis was more common in those with popliteal cyst (36.2%
      versus 9.7%, P <0.01). In multivariable analyses, popliteal cysts were
      significantly associated with increased osteophytes in both medial and lateral
      tibiofemoral compartments while subgastrocnemius bursitis was associated with
      increased osteophytes and JSN in the medial tibiofemoral compartment. Both were
      significantly associated with cartilage defects in all compartments, and with
      BMLs in the medial tibiofemoral compartment. Furthermore, both popliteal cysts
      and subgastrocnemius bursitis were significantly associated with increased weight
      bearing knee pain but these associations became non-significant after adjustment
      for cartilage defects and BMLs. CONCLUSIONS: Popliteal cysts and subgastrocnemius
      bursitis are associated with increased symptoms as well as radiographic and MRI
      detected joint structural abnormalities. Longitudinal data will help resolve if
      they are a consequence or a cause of knee joint abnormalities.

PMID- 24581328
TI  - The knowledge, attitudes and practices of wintersun vacationers to the Gambia
      toward prevention of malaria: is it really that bad?
AB  - BACKGROUND: Each year clusters of imported malaria cases are observed in Dutch
      wintersun vacationers returning from The Gambia. To gain more insight in the
      travel health preparation and awareness of these travellers, the knowledge,
      attitudes and practices (KAP) of this travel group was studied by analysing the
      data of the Continuous Dutch Schiphol Airport Survey. METHODS: In the years 2002
      to 2009 a questionnaire-based survey was conducted at the Dutch Schiphol Airport
      with the aim to study the KAP, i.e. accuracy of risk perception ("knowledge"),
      intended risk-avoiding behaviour ("attitude") and use of personal protective
      measures and malaria chemoprophylaxis ("practice") toward prevention malaria in
      travellers to The Gambia. Travellers to other high-risk destinations served as
      controls. RESULTS: The KAP of travellers to The Gambia toward prevention of
      malaria was significantly better than that observed in other travellers. Trend
      analyses indicated that attitude improved over time in both groups but knowledge
      did not change. Only in travellers to high-risk countries other than The Gambia
      significant increases in protection rates were observed over time. CONCLUSIONS:
      The KAP of travellers to The Gambia toward prevention of malaria was better than
      that observed in travellers to destinations other than The Gambia. Trend analyses
      revealed a significant improvement of intended risk avoiding behaviour but not in
      protection rates or risk perception.

PMID- 24581329
TI  - 'Changing minds': determining the effectiveness and key ingredients of an
      educational intervention to enhance healthcare professionals' intentions to
      prescribe physical activity to patients with physical disabilities.
AB  - BACKGROUND: Healthcare professionals (HCPs) are vital conduits of leisure-time
      physical activity (LTPA) information; however, few discuss LTPA with their
      patients with disabilities. 'Changing Minds, Changing Lives' (CMCL) is a
      nationwide, theory- and evidence-based seminar aimed at increasing LTPA
      discussion among HCPs by enhancing their attitudes, subjective norms, perceived
      behavioural control (PBC), and intentions. The purposes of the current study were
      to: examine the effectiveness and short- and long-term maintenance of a CMCL
      seminar on HCPs' social cognitions to discuss LTPA; and explore key
      implementation variables that predict changes in HCPs' social cognitions.
      METHODS: Prior-to, as well as immediately, one, and six months following a CMCL
      seminar, 97 HCPs (Mage +/- SD = 36.23 +/- 10.42; 69.0% female; 97.9% Caucasian;
      38.1% rehabilitation therapists; years in profession = 11.56 +/- 9.94) from five
      Canadian provinces completed questionnaires that assessed the Theory of Planned
      Behaviour constructs with regard to discussing LTPA with their patients with a
      physical disability. Key presenter characteristics and intervention delivery
      components were extracted from presenter demographic questionnaires and seminar
      checklists, respectively. Separate repeated-measures ANOVAs and post-hoc t-tests
      evaluated changes in HCPs' social cognitions. Hierarchical multiple regressions
      were conducted to predict intentions and to understand which implementation
      variables may help explain significant changes in social cognitions. RESULTS:
      Significant increases in HCPs' social cognitions for discussing LTPA were
      reported from pre- to post-seminar (ps <0.002); however, increases were not
      maintained at follow-up. PBC emerged as the strongest predictor of participants'
      post-CMCL intentions (beta = 0.45, p <0.001). Although several implementation
      characteristics were related to changes in perceptions, the number of seminars
      the presenter delivered was the only significant negative predictor of post
      seminar PBC (beta = -0.18, p <0.05). CONCLUSIONS: Future iterations of the CMCL
      intervention should include additional strategies to sustain improvements in
      HCPs' social cognitions over time. Future CMCL evaluations should measure
      additional implementation variables so that the key ingredients for 'Changing
      Minds' can continue to be investigated.

PMID- 24581330
TI  - Perioperative patient safety indicators and hospital surgical volumes.
AB  - BACKGROUND: Since the late 1990s, patient safety has been an important policy
      issue in developed countries. To evaluate the effectiveness of the activities of
      patient safety, it is necessary to quantitatively assess the incidence of adverse
      events by types of failure mode using tangible data. The purpose of this study is
      to calculate patient safety indicators (PSIs) using the Japanese Diagnosis
      Procedure Combination/per-diem payment system (DPC/PDPS) reimbursement data and
      to elucidate the relationship between perioperative PSIs and hospital surgical
      volume. METHODS: DPC/PDPS data of the Medi-Target project managed by the All
      Japan Hospital Association were used. An observational study was conducted where
      PSIs were calculated using an algorithm proposed by the US Agency for Healthcare
      Research and Quality. We analyzed data of 1,383,872 patients from 188 hospitals
      who were discharged from January 2008 to December 2010. RESULTS: Among 20
      provider level PSIs, four PSIs (three perioperative PSIs and decubitus ulcer) and
      mortality rates of postoperative patients were related to surgical volume. Low
      volume hospitals (less than 33rd percentiles surgical volume per month) had
      higher mortality rates (5.7%, 95% confidence interval (CI), 3.9% to 7.4%) than
      mid- (2.9%, 95% CI, 2.6% to 3.3%) or high-volume hospitals (2.7%, 95% CI, 2.5% to
      2.9%). Low-volume hospitals had more deaths among surgical inpatients with
      serious treatable complications (38.5%, 95% CI, 33.7% to 43.2%) than high-volume
      hospitals (21.4%, 95% CI, 19.0% to 23.9%). Also Low-volume hospitals had lower
      proportion of difficult surgeries (54.9%, 95% CI, 50.1% to 59.8%) compared with
      high-volume hospitals (63.4%, 95% CI, 62.3% to 64.6%). In low-volume hospitals,
      limited experience may have led to insufficient care for postoperative
      complications. CONCLUSIONS: We demonstrated that PSIs can be calculated using
      DPC/PDPS data and perioperative PSIs were related to hospital surgical volume.
      Further investigations focusing on identifying risk factors for poor PSIs and
      effective support to these hospitals are needed.

PMID- 24581331
TI  - Fibroblasts isolated from a keratocystic odontogenic tumor promote
      osteoclastogenesis in vitro via interaction with epithelial cells.
AB  - OBJECTIVES: Investigate the role of the epithelial-mesenchymal interaction of
      keratocystic odontogenic tumor (KCOT) in influencing osteoclastogenesis.
      MATERIALS AND METHODS: Fibroblasts isolated from KCOT fibrous capsule and normal
      gingival mucosa were, respectively, co-cultured with human immortalized oral
      epithelial cells (HIOECs), and the supernatant was collected to make conditioned
      medium, in which the osteoclastogenesis of osteoclast precursor cell line Raw
      264.7 was observed. Genes related to bone resorption (RANKL, OPG, COX-2, and M
      CSF) were analyzed by real-time PCR. Antibodies against human sRANKL and
      inhibitor of COX-2: NS398 were added to conditioned medium to investigate the
      inhibitory effect on osteoclastogenesis. RESULTS: Compared with co-cultured
      gingival fibroblasts and HIOECs (GE-CM), the conditioned medium from co-cultured
      KCOT fibroblasts and HIOECs (KE-CM) induced more osteoclast-like cell formation
      and increased NFATC1 mRNA in Raw264.7 cells (P < 0.05). Co-cultured KCOT
      fibroblasts (KF) and HIOECs, respectively, expressed more COX-2 mRNA than the co
      cultured gingival fibroblasts (GF) and HIOECs (P < 0.05). While the ratio of
      RANKL/OPG in HIOECs co-cultured with KF was also significantly higher than that
      co-cultured with GF (P < 0.05). The anti-human sRANKL antibody in KE-CM inhibited
      osteoclastogenesis of Raw264.7 cells; however, NS398 displayed little inhibition.
      CONCLUSION: An interesting phenomenon of osteoclastogenic effect of KE-CM in
      vitro was investigated, which suggested an indispensable role of epithelial
      mesenchymal interaction of KCOT in its bone destruction. It could be at least
      partly attributed to the up-regulated ratio of RANKL/OPG in epithelium induced by
      KCOT fibroblasts, the aggressiveness of tumor as result of epithelial-mesenchymal
      interaction deserves exploration further.

PMID- 24581332
TI  - The mediating role of self-efficacy in the relationship between Big five
      personality and depressive symptoms among Chinese unemployed population: a cross
      sectional study.
AB  - BACKGROUND: Besides the rapid growth of economy, unemployment becomes a severe
      socio-economic problem in China. The huge population base in China makes the
      unemployed population a tremendously huge number. However, health status of
      unemployed population was ignored and few studies were conducted to describe the
      depressive symptoms of unemployed individuals in China. This study aims to
      examine the relationship between Big five personality and depressive symptoms and
      the mediating role of self-efficacy in this relationship. METHODS: This cross
      sectional study was performed during the period of July to September 2011.
      Questionnaires consisting of the Center for Epidemiologic Studies Depression
      Scale (CES-D), the Big Five Inventory (BFI) and the General Self-efficacy Scale
      (GSE), as well as demographic factors, were used to collect information of
      unemployed population. A total of 1,832 individuals (effective response rate:
      73.28%) became our subjects. Hierarchical linear regression analyses were
      performed to explore the mediating role of self-efficacy. RESULTS: The prevalence
      of depressive symptoms was 67.7% among Chinese unemployed individuals. After
      adjusting for demographic characteristics, extraversion, agreeableness and
      conscientiousness were all negatively associated with depressive symptoms whereas
      neuroticism was positively associated with depressive symptoms. The proportion of
      mediating effect of self-efficacy in the relationship between
      extraversion/agreeableness/conscientiousness/neuroticism and depressive symptoms
      was 25.42%, 10.91%, 32.21% and 36.44%, respectively. Self-efficacy is a mediator
      in the relationship between
      extraversion/agreeableness/conscientiousness/neuroticism and depressive symptoms.
      CONCLUSION: Self-efficacy partially mediated the relationship between Big five
      personality and depressive symptoms among Chinese unemployed individuals.
      Interventions that focus on both individuals' personality and self-efficacy may
      be most successful to reduce depressive symptoms of unemployed individuals.

PMID- 24581333
TI  - Rheumatic heart disease in Uganda: the association between MHC class II HLA DR
      alleles and disease: a case control study.
AB  - BACKGROUND: Rheumatic heart disease (RHD), the only long term consequence of
      acute rheumatic fever, remains a leading cause of morbidity and mortality among
      young adults in Uganda. An inherited susceptibility to acute rheumatic fever
      centers around the major histocompatibility class II human leucocyte antigens.
      However, there is paucity of data from sub-Saharan Africa. This study compares
      the frequency of HLA class II DR alleles between RHD cases and normal controls in
      Uganda. METHODS: One hundred ninety-nine participants including 96 established
      RHD cases aged 5-60 years and 103 age and sex matched normal controls were
      recruited for participation. DNA was manually extracted from buffy coat samples
      and HLA analysis was performed. HLA-DR allelic frequency comparison between cases
      and controls were estimated using conditional logistic regression with 95%
      confidence intervals. P -values were corrected for multiple hypothesis testing.
      RESULTS: 199 participants (103 female, 51.8%) completed the study. The mean (SD)
      age in years for cases and controls were 29.6 (10.2) and 29(18), respectively.
      After conditional logistic regression and multiple hypothesis testing, HLA-DR1was
      associated with a decreased risk of RHD (OR = 0.42, CI 0.21-085, P = 0.01,
      Corrected P value (PC) = 0.09,) while HLA-DR11 was associated with increased risk
      of RHD (OR = 3.31, CI 1.57-6.97, P = <0.001, Pc < 0.001). No other significant
      associations were found. CONCLUSION: In this first study of HLA genetic
      susceptibility to RHD in Uganda, HLA- DR1 was more common in normal controls
      while HLA- DR11 was more common among RHD cases suggesting a disease
      susceptibility association. In future studies, high resolution HLA analysis and
      genome wide studies should be carried out to confirm this pattern.

PMID- 24581334
TI  - A 12-year comparison of students' perspectives on diversity at a Jesuit Medical
      School.
AB  - BACKGROUND: Many studies have assessed perspectives of medical students toward
      institutional diversity, but few of them have attempted to map changes in
      diversity climate over time. OBJECTIVE: This study aims to investigate changes in
      diversity climate at a Jesuit medical institution over a 12-year period. METHODS:
      In 1999, 334 medical students completed an anonymous self-administered online
      survey, and 12 years later, 406 students completed a comparable survey in 2011.
      Chi-square tests assessed the differences in percent responses to questions of
      the two surveys, related to three identities: gender, race, and sexual
      orientation. RESULTS: The 1999 versus 2011 samples were 46% versus 49% female,
      61% versus 61% Caucasian, and 41% vs. 39% aged 25 years or older. Findings
      suggested improvements in medical students' perceptions surrounding equality 'in
      general' across the three identities (p<0.001); 'in the practice of medicine'
      based on gender (p<0.001), race/ethnicity (p=0.60), and sexual orientation
      (p=0.43); as well as in the medical school curriculum, including course text
      content, professor's delivery and student-faculty interaction (p<0.001) across
      the three identities. There was a statistically significant decrease in
      experienced or witnessed events related to gender bias (p<0.001) from 1999 to
      2011; however, reported events of bias based on race/ethnicity (p=0.69) and
      sexual orientation (p=0.58) only showed small decreases. CONCLUSIONS: It may be
      postulated that the improvement in students' self-perceptions of equality and
      diversity over the past 12 years may have been influenced by a generational
      acceptance of cultural diversity and, the inclusion of diversity training courses
      within the medical curriculum. Diversity training related to race and sexual
      orientation should be expanded, including a follow-up survey to assess the
      effectiveness of any intervention.

PMID- 24581335
TI  - Expanded HIV testing in high-prevalence areas in England: results of a 2012 audit
      of sexual health commissioners.
AB  - OBJECTIVES: The aim of the study was to examine whether UK HIV testing guidelines
      which recommend the expansion of HIV testing in high HIV prevalence areas have
      been implemented in England. METHODS: An online survey tool was used to conduct
      an audit of sexual health commissioners in 40 high HIV prevalence areas
      (diagnosed prevalence > 2 per 1000) between May and June 2012. Responders were
      asked to provide details of expanded HIV testing programmes that they had
      commissioned in nontraditional settings and perceived barriers and facilitators
      involved in introducing expanded testing. RESULTS: The response rate was 88% (35
      of 40). Against the key audit standards, 31% (11 of 35) of areas had commissioned
      routine testing of new registrants in general practice, and 14% (five of 35)
      routine testing of general medical admissions. The majority of responders (80%;
      28 of 35) had commissioned some form of expanded testing, often targeted at risk
      groups. The most common setting for commissioning of testing was the community
      (51%; 18 of 35), followed by general practice (49%; 17 of 35) and hospital
      departments (36%; 13 of 35). A minority (11%; four of 35) of responders had
      commissioned testing in all three settings. Where testing in general practice
      took place this was typically in a minority of practices (median 10-20%). Most
      (77%; 27 of 35) expected the rate of HIV testing to increase over the next year,
      but lack of resources was cited as a barrier to testing by 94% (33 of 35) of
      responders. CONCLUSIONS: Not all high HIV prevalence areas in England have fully
      implemented testing guidelines. Scale-up of existing programmes and continued
      expansion of testing into new settings will be necessary to achieve this.

PMID- 24581337
TI  - Socio-occupational class, region of birth and maternal age: influence on time to
      detection of cryptorchidism (undescended testes): a Danish nationwide register
      study.
AB  - BACKGROUND: Cryptorchidism (undescended testes) is associated with poor male
      fertility, but can be alleviated and fertility preserved to some degree by early
      detection and treatment. Here we assess the influence of socio-occupational
      class, geographical region, maternal age and birth cohort on time to detection
      and correction of cryptorchidism. METHODS: All boys born in Denmark, 1981 to 1987
      or 1988 to 1994, with a diagnosis of cryptorchidism were identified in nationwide
      registers. The boys were followed for a diagnosis until their 16th birthday. The
      age at first diagnosis was noted and used as proxy for time to detection of
      cryptorchidism. Parental employment in the calendar year preceding birth was
      grouped into one of five socio-occupational classes. Geographical region was
      defined by place of birth in one of 15 Danish counties. Detection rate ratios of
      cryptorchidism were analyzed as a function of parental socio-occupational group,
      county, maternal age and birth cohort by use of Poisson regression. RESULTS: Some
      6,059 boys in the early and 5,947 boys in the late cohort received a diagnosis of
      cryptorchidism. Time to detection was independent of parental socio-occupational
      group and maternal age but differed slightly between geographical regions. A
      similar pattern was obtained for surgical correction after a diagnosis. Age at
      diagnosis decreased by 2.7 years from the early to the late cohort. CONCLUSIONS:
      These results indicate that childhood socio-occupational inequality in detection
      and correction of cryptorchidism would play a negligible role in male infertility
      in a life course perspective. Geographical region may have exerted some
      influence, especially for the oldest cohort.

PMID- 24581338
TI  - Mefloquine safety and tolerability in pregnancy: a systematic literature review.
AB  - BACKGROUND: Control of malaria in pregnant women is still a major challenge as it
      constitutes an important cause of maternal and neonatal mortality. Mefloquine
      (MQ) has been used for malaria chemoprophylaxis in non-immune travellers for
      several decades and it constitutes a potential candidate for intermittent
      preventive treatment in pregnant women (IPTp). METHODS: The safety of MQ,
      including its safety in pregnancy, is controversial and a continuing subject of
      debate. Published studies which evaluated the use of MQ for malaria prevention or
      treatment in pregnant women and which reported data on drug tolerability and/or
      pregnancy outcomes have been reviewed systematically. RESULTS: Eighteen articles
      fitted the inclusion criteria, only one study was double-blind and placebo
      controlled. No differences were found in the risk of adverse pregnancy outcomes
      in women exposed to MQ compared to those exposed to other anti-malarials or to
      the general population. MQ combined with artesunate seems to be better tolerated
      than standard quinine therapy for treatment of non-severe falciparum malaria, but
      a MQ loading dose (10 mg/kg) is associated with more dizziness compared with
      placebo. When used for IPTp, MQ (15 mg/kg) may have more side effects than
      sulphadoxine- pyrimethamine. CONCLUSIONS: In the published literature there are
      no indications that MQ use during pregnancy carries an increased risk for the
      foetus. Ideally, the use of MQ to prevent malaria should be based on a risk
      benefit analysis of adverse effects against the risk of acquiring the infection.
      For this purpose double-blinded randomized controlled trials in African pregnant
      women are much needed.

PMID- 24581339
TI  - Understanding diagnosis and management of dementia and guideline implementation
      in general practice: a qualitative study using the theoretical domains framework.
AB  - BACKGROUND: Dementia is a growing problem, causing substantial burden for
      patients, their families, and society. General practitioners (GPs) play an
      important role in diagnosing and managing dementia; however, there are gaps
      between recommended and current practice. The aim of this study was to explore
      GPs' reported practice in diagnosing and managing dementia and to describe, in
      theoretical terms, the proposed explanations for practice that was and was not
      consistent with evidence-based guidelines. METHODS: Semi-structured interviews
      were conducted with GPs in Victoria, Australia. The Theoretical Domains Framework
      (TDF) guided data collection and analysis. Interviews explored the factors
      hindering and enabling achievement of 13 recommended behaviours. Data were
      analysed using content and thematic analysis. This paper presents an in-depth
      description of the factors influencing two behaviours, assessing co-morbid
      depression using a validated tool, and conducting a formal cognitive assessment
      using a validated scale. RESULTS: A total of 30 GPs were interviewed. Most GPs
      reported that they did not assess for co-morbid depression using a validated tool
      as per recommended guidance. Barriers included the belief that depression can be
      adequately assessed using general clinical indicators and that validated tools
      provide little additional information (theoretical domain of 'Beliefs about
      consequences'); discomfort in using validated tools ('Emotion'), possibly due to
      limited training and confidence ('Skills'; 'Beliefs about capabilities'); limited
      awareness of the need for, and forgetting to conduct, a depression assessment
      ('Knowledge'; 'Memory, attention and decision processes'). Most reported
      practising in a manner consistent with the recommendation that a formal cognitive
      assessment using a validated scale be undertaken. Key factors enabling this were
      having an awareness of the need to conduct a cognitive assessment ('Knowledge');
      possessing the necessary skills and confidence ('Skills'; 'Beliefs about
      capabilities'); and having adequate time and resources ('Environmental context
      and resources'). CONCLUSIONS: This is the first study to our knowledge to use a
      theoretical approach to investigate the barriers and enablers to guideline
      recommended diagnosis and management of dementia in general practice. It has
      identified key factors likely to explain GPs' uptake of the guidelines. The
      results have informed the design of an intervention aimed at supporting practice
      change in line with dementia guidelines, which is currently being evaluated in a
      cluster randomised trial.

PMID- 24581341
TI  - BCLA Pioneers Lecture - evidence basis for patient selection: how to predict
      contact lens success.

PMID- 24581342
TI  - Intercalibration of ecological quality in European Mediterranean rivers.

PMID- 24581340
TI  - Effect of glomerular filtration rate impairment on diagnostic performance of
      neutrophil gelatinase-associated lipocalin and B-type natriuretic peptide as
      markers of acute cardiac and renal failure in chronic kidney disease patients.
AB  - INTRODUCTION: Cardio-renal syndromes are characterized by the impairment of
      cardiac and renal functions. Plasma and urinary neutrophil gelatinase-associated
      lipocalin (NGAL), and plasma B-type natriuretic peptide (BNP) are markers of
      acute kidney injury (AKI) and heart failure (HF), respectively. METHODS: GFR
      (99mTc-DTPA), plasma BNP, and plasma and urinary concentrations of NGAL were
      measured in 310 clinically stable CKD patients, at functional stages from 1 to 5.
      Serum and urinary low-molecular-weight proteins cystatin C and beta2
      microglobulin, and urinary tubular enzymes were measured for comparison. Plasma
      BNP, NGAL, cystatin C and beta2-microglobulin were measured also in 31
      maintenance hemodialysis patients. RESULTS: Plasma NGAL increased with the
      reduction of GFR in CKD patients from stage 2. In the different CKD stages modest
      differences were found for BNP values. Urinary NGAL increased slightly but
      significantly in patients at CKD stages 4 and 5, similarly to urinary cystatin C
      and beta2-microglobulin. In maintenance hemodialysis patients, plasma NGAL and
      BNP were markedly increased, and high-flux hemodialysis significantly decreased
      their plasma concentrations. CONCLUSIONS: Plasma NGAL increases markedly with the
      reduction in GFR, generating a very high number of false positive diagnoses of
      AKI in stable CKD patients. The grade of GFR impairment and the cause of kidney
      disease have a lower effect on urinary NGAL and on plasma BNP. In any case,
      specific reference values of NGAL and BNP should be used in chronic kidney
      disease patients, according to their functional stage, when assessing acute
      kidney injury, heart failure, and cardio-renal syndromes in patients with
      impaired GFR.

PMID- 24581343
TI  - Aberrant DNA methylation status of DNA repair genes in breast cancer treated with
      neoadjuvant chemotherapy.
AB  - Dysregulation of homologous recombination (HR) DNA repair has been implicated in
      breast carcinogenesis and chemosensitivity. Here, we investigated the methylation
      status of sixteen HR genes and analyzed their association with tumor subtypes and
      responses to neoadjuvant chemotherapy. Core specimens were obtained before
      neoadjuvant chemotherapy from sixty cases of primary breast cancer of the
      following four subgroups: luminal breast cancer (LBC) with pathological complete
      response (pCR), LBC with stable disease, triple-negative breast cancer (TNBC)
      with pCR and TNBC with poor response. The aberrant DNA methylation status of the
      following HR related-genes was analyzed using bisulfite-pyrosequencing: BRCA1,
      BRCA2, BARD1, MDC1, RNF8, RNF168, UBC13, ABRA1, PALB2, RAD50, RAD51, RAD51C,
      MRE11, NBS1, CtIP and ATM. Among the genes analyzed, only the incidence of BRCA1
      and RNF8 methylation was significantly higher in TNBC than that in LBC. Whereas
      the incidence of BRCA1 methylation was tended to be higher in pCR cases than in
      poor-response cases in TNBC, that of RNF8 was significantly lower in pCR cases
      than in poor-response cases. Our results indicate that the methylation status of
      HR genes was not generally associated with TNBC subtype or chemosensitivity
      although hypermethylation of BRCA1 is associated with TNBC subtype and may impact
      chemosensitivity. 

PMID- 24581345
TI  - Intravascular fasciitis involving the flank of a 21-year-old female: a case
      report and review of the literature.
AB  - BACKGROUND: Intravascular fasciitis is an uncommon variant of nodular fasciitis,
      which is a reactive proliferative lesion of myofibroblasts. Since its
      identification in 1981, only 32 cases of intravascular fasciitis have been
      reported in the English literature. The lesion is commonly located in the head,
      neck, and extremities, with only three cases arising from the trunk. Here we
      report the fourth case involving the trunk (the flank area). CASE PRESENTATION: A
      21-year-old African-American female presented with a subcutaneous mass on her
      flank. Grossly, the mass was red-tan, oval, and well-demarcated, measuring
      approximately 0.5 cm in diameter. Microscopically, the mass was composed of
      spindle cells arranged in a swirling and intersecting pattern inside the lumens
      of two blood vessels. It extended through the vascular walls into the surrounding
      fibroadipose tissue; in some sections, the spindle cells were intermixed with the
      perivascular fibrous tissue. Elastin stain revealed remnants of elastic lamina
      partially surrounding the lesion. The nuclei of the spindle cells were relatively
      uniform with tapered ends and prominent nucleoli. No significant mitotic activity
      was observed. Multinucleated giant cells were scattered among the spindle cells,
      along with infiltrating lymphocytes and extravasated red blood cells.
      Immunohistochemical stains showed the spindle cells were positive for smooth
      muscle actin, focally positive for muscle specific actin, and negative for S-100,
      confirming their myofibroblastic differentiation. The overall morphological and
      immunohistochemical features are consistent with intravascular fasciitis.
      CONCLUSION: By reporting this rare case, we would like to raise the awareness of
      this non-neoplastic lesion to avoid misdiagnosing it as a sarcoma with vascular
      invasion. Previously reported similar cases were also reviewed and compared with
      this case.

PMID- 24581344
TI  - Manipulation of valve composition to elucidate the role of collagen in aortic
      valve calcification.
AB  - BACKGROUND: Extracellular matrix (ECM) disarray is found in calcific aortic
      valvular disease (CAVD), yet much remains to be learned about the role of
      individual ECM components in valvular interstitial cell (VIC) function and
      dysfunction. Previous clinical analyses have shown that calcification is
      associated with decreased collagen content, while previous in vitro work has
      suggested that the presence of collagen attenuates the responsiveness of VICs to
      pro-calcific stimuli. The current study uses whole leaflet cultures to examine
      the contributions of endogenous collagen in regulating the phenotype and
      calcification of VICs. METHODS: A "top-down" approach was used to characterize
      changes in VIC phenotype in response to collagen alterations in the native 3D
      environment. Collagen-deficient leaflets were created via enzymatic treatment and
      cultured statically for six days in vitro. After culture, leaflets were harvested
      for analysis of DNA, proliferation, apoptosis, ECM composition, calcification,
      and gene/protein expression. RESULTS: In general, disruption of collagen was
      associated with increased expression of disease markers by VICs in whole organ
      leaflet culture. Compared to intact control leaflets, collagen-deficient leaflets
      demonstrated increased VIC proliferation and apoptosis, increased expression of
      disease-related markers such as alpha-smooth muscle actin, alkaline phosphatase,
      and osteocalcin, and an increase in calcification as evidenced by positive von
      Kossa staining. CONCLUSIONS: These results indicate that disruption of the
      endogenous collagen structure in aortic valves is sufficient to stimulate
      pathological consequences in valve leaflet cultures, thereby highlighting the
      importance of collagen and the valve extracellular matrix in general in
      maintaining homeostasis of the valve phenotype.

PMID- 24581346
TI  - A survey of adult anophelines in French Guiana: enhanced descriptions of species
      distribution and biting responses.
AB  - In French Guiana, Anopheles darlingi is considered the main malaria vector.
      However, several reports have hypothesized the implication of other anopheline
      species in malaria transmission for the territory. Data on the ecology of these
      other potential vectors is rare or even unexplored in French Guiana. The aim of
      this study was to describe the biting habits of several anopheline species in
      multiple localities in French Guiana. Six sampling sites yielded 1,083 anopheline
      adults. Results indicated the presence of An. darlingi in all study locations and
      it was the only species to be collected inside villages. Other anophelines
      collected included An. aquasalis, An. braziliensis, An. intermedius, An.
      mediopunctatus, An. nuneztovari, An. oswaldoi, and An. triannulatus, all of which
      were associated with open areas and forests. The environment and time, at which
      biting behavior was recorded, varied for each species. It was noted that An.
      oswaldoi showed a daytime rhythm in open areas. This study is the first to report
      on the biting habits of a range of anophelines in French Guiana that may play a
      role in malaria transmission. This information is vital to fully describe the
      risk of malaria transmission and thereby design appropriate vector control
      measures and malaria prevention programs. 

PMID- 24581347
TI  - Experimental infection of Eurasian collared-dove (Streptopelia decaocto) with
      West Nile virus.
AB  - The Eurasian collared-dove (Streptopelia decaocto) has recently experienced a
      population explosion in North America. It is frequently infected with West Nile
      virus (WNV). To test the hypothesis that the Eurasian collared-dove is competent
      to transmit WNV, we experimentally infected two cohorts of doves with two
      different strains of WNV, CO08, and NY99, respectively. Both virus strains
      induced a low-level viremia, capable of infecting a small fraction of vector
      mosquitoes. We suggest that the Eurasian collared-dove plays a relatively
      insignificant role as an amplifying host for WNV, but it may be important where
      it is locally abundant. 

PMID- 24581348
TI  - Effect of habitat complexity on the predation of Buenoa fuscipennis (Heteroptera:
      Notonectidae) on mosquito immature stages and alternative prey.
AB  - Notonectids are well-known predators in aquatic habitats, where mosquito larvae,
      chironomids, and cladocerans constitute their main diet. Our purpose was to
      assess the effect of structural complexity on the predatory ability of Buenoa
      fuscipennis, a common predator in aquatic habitats of Buenos Aires city
      (Argentina). Buenoa fuscipennis showed type 2 functional responses in both the
      presence and absence of prey refuge and no differences in attack rate or handling
      time between refuge treatments. Regarding mosquito size classes, B. fuscipennis
      exhibited a significantly higher preference for 2(nd) instar larvae and no
      predation on pupae. In the presence of mosquito larvae and alternative prey, B.
      fuscipennis preferred mosquitoes over chironomid larvae and adult cladocerans
      over mosquito larvae. No switching behavior was detected in our experiments.
      Habitat structure only slightly affected the predator's consumption rates on
      mosquito larvae. Overall, preference for prey did not vary with the presence of
      refuge, except for the preference for mosquitoes over chironomid larvae, which
      was significantly decreased in the presence of refuge as a consequence of reduced
      predation on mosquito larvae. The results suggest that B. fuscipennis could
      efficiently control mosquitoes in structurally simple habitats where chironomids
      are the most abundant alternative prey but not in temporary pools where
      cladocerans are abundant. 

PMID- 24581349
TI  - Climatic factors and population density of Lutzomyia longipalpis (Lutz & Neiva,
      1912) in an urban endemic area of visceral leishmaniasis in midwest Brazil.
AB  - The life cycle of vectors and the reservoirs that participate in the chain of
      infectious diseases have a strong relationship with the environmental dynamics of
      the ecosystems in which they live. Oscillations in population abundance and
      seasonality of insects can be explained by factors inherent in each region and
      time period. Therefore, knowledge of the relationship and influence of
      environmental factors on the population of Lutzomyia longipalpis is necessary
      because of the high incidence of visceral leishmaniasis (VL) in Brazil. This
      study evaluates the influence of abiotic variables on the population density and
      seasonal behavior of L. longipalpis in an urban endemic area of VL in Brazil. The
      sand fly captures were performed every two months between November, 2009 and
      November, 2010 in the peridomicile of 13 randomly selected residences. We
      captured 1,367 specimens of L. longipalpis, and the ratio of male/female flies
      was 2.86:1. The comparison of the total male specimens in the two seasons showed
      a statistical difference in the wet season, but there was no significant
      difference when considering the total females. With respect to climatic
      variables, a significant negative association was observed only with wind speed.
      During periods of high wind speeds, the population density of this vector
      decreased. The presence of L. longipalpis was found in all months of the study
      with bimodal behavior and population peaks during the wet season. 

PMID- 24581350
TI  - Patterns of spatio-temporal distribution, abundance, and diversity in a mosquito
      community from the eastern Smoky Hills of Kansas.
AB  - Nearly 30% of emerging infectious disease events are caused by vector-borne
      pathogens with wildlife origins. Their transmission involves a complex interplay
      among pathogens, arthropod vectors, the environment and host species, and they
      pose a risk for public health, livestock and wildlife species. Examining habitat
      associations of vector species known to transmit infectious diseases, and
      quantifying spatio-temporal dynamics of mosquito vector communities is one aspect
      of the holistic One Health approach that is necessary to develop effective
      control measures. A survey was conducted from May to August, 2010 of the
      abundance and diversity of mosquito species occurring in the mixed-grass prairie
      habitat of the Smoky Hills of Kansas. This region is an important breeding ground
      for North America's grassland nesting birds and, as such, it could represent an
      important habitat for the enzootic amplification cycle of avian malaria and
      infectious encephalitides, as well as spill-over events to humans and livestock.
      A total of 11 species, belonging to the three genera Aedes, Anopheles, and Culex,
      was collected during this study. Aedes nigromaculis, Ae. sollicitans, Ae.
      taeniorhynchus, Culex salinarius, and Cx. tarsalis accounted for 98% of the
      collected species. Multiple linear regression models suggested that mosquito
      abundances in the grasslands of the central Great Plains were explained by
      meteorological and environmental variables. Temporal dynamics in mosquito
      abundances were well supported by models that included maximum and minimum
      temperature indices (adjusted R(2) = 0.73). Spatial dynamics of mosquito
      abundances were best explained by a model containing the following environmental
      variables (adjusted R(2) =0.37): ground curvature, topographic wetness index,
      distance to woodland, and distance to road. The mosquito species we detected are
      known vectors for infectious encephalitides, including West Nile virus.
      Understanding the microhabitat characteristics of these mosquito species in a
      grassland ecosystem will aid in the control and management of these disease
      vectors. 

PMID- 24581351
TI  - Aedes species in treeholes and fruit husks between dry and wet seasons in
      southeastern Senegal.
AB  - During the dry season in February, 2010 and the wet season in September, 2011 we
      sampled mosquito larvae and eggs from treeholes of seven native hardwood species
      and the husks of Saba senegalensis in 18 sites in the PK-10 forest in
      southeastern Senegal. Larvae were reared to adults for species identification. In
      the dry season, we recovered 408 Aedes mosquitoes belonging to seven species.
      Aedes aegypti s.l. comprised 42.4% of the collection, followed by Ae. unilineatus
      (39%). In contrast to reports from East Africa, both Ae. aegypti aegypti and Ae.
      aegypti formosus were recovered, suggesting that both subspecies survive the dry
      season in natural larval habitats in West Africa. In the wet season, 455
      mosquitoes were collected but 310 (68.1%) were the facultatively predaceous
      mosquito Eretmapodites chrysogaster. The remaining 145 mosquitoes consisted of
      ten Aedes species. Aedes aegypti s.l. comprised 55.1% of these, followed by Ae.
      apicoargenteus (15.2%) and Ae. cozi (11.7%). Similar to East Africa, most (90%)
      of Ae. aegypti s.l. in the wet season were subspecies formosus. 

PMID- 24581352
TI  - Evaluation of a CO2 -free commercial mosquito attractant to capture triatomines
      in the laboratory.
AB  - Efforts have been made to develop vertebrate odor-based attractants to lure
      hematophagous triatomines into traps. However, more work is needed to reach a
      practical, cheap, and efficient odor lure. We carried out attraction and capture
      tests in a dual-choice olfactometer and a pitfall trap. Here we report that a
      three-component, CO2 -free, synthetic blend of vertebrate odor (consisting of
      ammonia, L(+) lactic acid and hexanoic acid, and known as Sweetscent(r))
      significantly induces 3(rd) -instar Rhodnius prolixus and Triatoma infestans
      nymphs to fall into the test capture-tube of the olfactometer. Blend constituents
      presented singly or in two-component blends did not evoke a response and,
      therefore, we propose that the insects respond specifically to the three
      component blend in a synergistic way. When tested in a pitfall trap in an
      experimental arena, this blend induced capture in 37.5% of the lured traps,
      whereas 9% of the nymphs tested were captured in a single night. No insects were
      captured in control traps. Our work represents a proof-of-concept regarding
      capture of triatomines using host odor-based, CO2 -free synthetic mixtures as
      lures for pitfall traps. CO2 -free lures are more practical for field work than
      natural or CO2 -containing synthetic blends. 

PMID- 24581354
TI  - Characterization of two cryptic species, Culicoides stigma and C.parroti
      (Diptera: Ceratopogonidae), based on barcode regions and morphology.
AB  - Biting midges of the genus Culicoides (Diptera: Ceratopogonidae) are insect
      vectors of economically important veterinary diseases such as African horse
      sickness, bluetongue, and Schmallenberg virus. The identification of Culicoides
      based on morphological features can be difficult. Three species of biting midges,
      Culicoides nubeculosus, C. stigma, and C. parroti have emerged in the laboratory
      from mud collected around watering troughs on a farm in northern France. Emerging
      Culicoides were characterized morphologically and molecularly using molecular
      markers. The closely related species C. stigma and C.parroti showed highly
      divergent sequences for both mitochondrial (cytochrome B and cytochrome oxidase
      I) and ribosomal DNA first internal transcribed spacer. A RFLP based on a single
      restriction using the same enzyme (HaeIII) for both cytochrome C oxidase I and
      cytochrome B is proposed to identify these species. 

PMID- 24581353
TI  - A statistical model of Rift Valley fever activity in Egypt.
AB  - Rift Valley fever (RVF) is a viral disease of animals and humans and a global
      public health concern due to its ecological plasticity, adaptivity, and potential
      for spread to countries with a temperate climate. In many places, outbreaks are
      episodic and linked to climatic, hydrologic, and socioeconomic factors. Although
      outbreaks of RVF have occurred in Egypt since 1977, attempts to identify risk
      factors have been limited. Using a statistical learning approach (lasso
      regularized generalized linear model), we tested the hypotheses that outbreaks in
      Egypt are linked to (1) River Nile conditions that create a mosquito vector
      habitat, (2) entomologic conditions favorable to transmission, (3) socio-economic
      factors (Islamic festival of Greater Bairam), and (4) recent history of
      transmission activity. Evidence was found for effects of rainfall and river
      discharge and recent history of transmission activity. There was no evidence for
      an effect of Greater Bairam. The model predicted RVF activity correctly in 351 of
      358 months (98.0%). This is the first study to statistically identify risk
      factors for RVF outbreaks in a region of unstable transmission. 

PMID- 24581355
TI  - Cytogenetic, hybridization and molecular evidence of four cytological forms of
      Anopheles nigerrimus (Hyrcanus Group) in Thailand and Cambodia.
AB  - Thirteen isoline colonies of Anopheles nigerrimus were established from
      individual wild-caught females collected from cow-baited traps at locations in
      Thailand and Cambodia. Three types of X (X1 , X2 , X3 ) and 4 types of Y (Y1 , Y2
      , Y3 , Y4 ) chromosomes were recovered, according to differing amounts of extra
      heterochromatin. Four karyotypic forms were designed depending upon apparently
      distinct figures of X and Y chromosomes, i.e., Form A (X1 , X2 , X3 , Y1 ), B (X2
      , X3 , Y2 ), C (X1 , Y3 ), and D (X3 , Y4 ). Forms C and D were new metaphase
      karyotypes discovered in this study. Form A appeared to be common in both
      Thailand and Cambodia. Forms B and D were found to be rather specific to southern
      and northeastern Thailand, respectively, whereas Form C was confined to Cambodia.
      Hybridization experiments among the eight isoline colonies, which were
      representative of four karyotypic forms of An. nigerrimus, demonstrated genetic
      compatibility in giving viable progenies and synaptic salivary gland polytene
      chromosomes through F2 -generations. These results elucidated the conspecific
      relationship, comprising four cytological forms within this taxon. Supportive
      evidence was confirmed further by very low intraspecific sequence variations
      (average genetic distance = 0.002-0.007) of the nucleotide sequences in ribosomal
      DNA [second internal transcribed spacer (ITS2)] and mitochondrial DNA [cytochrome
      c oxidase subunit I (COI) and subunit II (COII)]. 

PMID- 24581356
TI  - A new tent trap for monitoring the daily activity of Aedes aegypti and Aedes
      albopictus.
AB  - In this study, we designed a new tent trap; the BioDiVector (BDV) tent trap,
      consisting of two rectangular tents that use human bait without endangering the
      technical personnel. The daily activity pattern of Aedes aegypti and Aedes
      albopictus in intra, peri, and extradomiciliary sites was studied in an endemic
      area of dengue in southern Mexico by using the BDV tent trap. Totals of 3,128
      individuals of Ae. aegypti and 833 Ae. albopictus were captured. More Ae. aegypti
      males than females were caught, while the opposite was true with Ae. albopictus.
      The activity of both mosquito species was affected by the interaction between the
      collection site and time of day. In general, more individuals of both mosquito
      species were captured at the extradomicillary sites than at the peri and
      intradomicillary sites. Mosquitoes showed two peaks of activity, one in the
      morning and the other in the afternoon, but in general this only occurred at the
      extradomicillary sites, whereas no peak of activity was observed at the intra and
      peridomicillary sites. Overall, Ae. aegypti had a higher indirect biting rate
      than Ae. albopictus. Finally, due to its efficiency, simplicity, and low cost, we
      suggest the use of this innovative tool for entomological surveillance, bionomics
      and vector incrimination studies in geographical areas where dengue and other
      arboviruses are present. 

PMID- 24581357
TI  - Blood, sweat, and tears: a review of the hematophagous, sudophagous, and
      lachryphagous Lepidoptera.
AB  - Although adult Lepidoptera are not often considered medically relevant, some
      butterflies and moths are notorious for their consumption of mammalian body
      fluids. These Lepidoptera can be blood-feeding (hematophagous), tear-feeding
      (lachryphagous), or sweat-feeding (we use the term "sudophagous"). Blood-feeding
      Lepidoptera have been observed piercing the skin of their hosts during feeding,
      while tear-feeding Lepidoptera have been observed frequenting the eyes of hosts
      in order to directly obtain lachrymal fluid. These behaviors have negative human
      health implications and some potential for disease transmission. In this study,
      articles concerning feeding behavior of blood, sweat, and tear-feeding
      Lepidoptera were reviewed, with emphasis on correlations between morphological
      characters and feeding behaviors. Harmful effects and vector potential of these
      Lepidoptera are presented and discussed. 

PMID- 24581358
TI  - Activity of the tick Ixodes ricinus monitored in a suburban park in Brno, Czech
      Republic, in association with the evaluation of selected repellents.
AB  - The ever-increasing number of Lyme borreliosis patients led us to consider more
      effective procedures for disease prevention. The aim of our study was to monitor
      the annual activity and infectivity of Ixodes ricinus ticks in the Pisarky
      region, City of Brno, CR, and to test the responses of the locally-captured ticks
      to selected repellents. The result of regular one-hour-per-week monitoring in
      2011 was the collection of ticks that directly reflected the highest number of
      Lyme disease patients (4,835) detected throughout the period of recording in the
      Czech Republic. The ticks were examined for spirochaetes by dark field
      microscopy. The positive samples were identified by PCR analysis, confirming that
      76% of these were infected with Borrelia burgdorferi sensu lato. Ticks were most
      abundant in May and June, with August having the highest risk for spirochaetal
      infection. Tick activity was statistically correlated with temperature. The
      moving-object-bioassay was used to study repellent efficiency on the Ixodes
      ricinus nymphs captured in the above-mentioned suburban park. Five selected
      commercial repellents based on DEET (N, N-diethyl-3-thylbenzamide) showed
      statistically different effects on the non-repellent control group.

PMID- 24581359
TI  - Effects of food, water depth, and temperature on diving activity of larval
      Anopheles gambiae sensu stricto: evidence for diving to forage.
AB  - Anopheles gambiae larvae have frequently been observed to dive, but the ecology
      of this behavior has not been extensively examined. We manipulated food level,
      water depth, and temperature for individually-reared larvae and observed diving
      activity. Larvae dived more often under low food, which suggests that they dive
      to forage. There was only weak evidence for effects of water depth or temperature
      on diving. Experimental results are discussed in the context of energy budgets.
      Understanding larval ecology of this species is important for predicting how it
      will respond to environmental change. Further study is needed to assess the role
      that larval diving plays in both feeding ecology and thermal regulation of this
      and other medically important species. 

PMID- 24581360
TI  - Ecological interactions among phlebotomines (Diptera: Psychodidae) in an
      agroforestry environment of northeast Brazil.
AB  - Phlebotomine vectors transmit parasites and can cause visceral leishmaniasis (VL)
      or cutaneous leishmaniasis (TL). Phlebotomine females are hematophagous but need
      to ingest carbohydrates, possibly promoting the development of protozoan
      parasites in their digestive tract. The present study evaluated the species
      composition and abundance across several habitats in a metropolitan landscape, as
      well as associations among phlebotomines, plants, and local climatic parameters.
      Three consecutive monthly collections were carried out in an Atlantic Forest
      fragment, using CDC light traps in peridomestic areas and cashew, coconut, and
      mango tree. plantations. Eight species of phlebotomine were captured: Evandromyia
      evandroi, Lutzomyia longipalpis, Psathyromyia shannoni, Sciopemyia sordellii,
      Evandromyia walkeri, Psychodopygus wellcomei, Nyssomyia whitmani, and Nyssomyia
      intermedia, primarily from the forest environment. L. longipalpis was confirmed
      as a species adapted to anthropic environments, while P. wellcomei was shown to
      be predominately forest-dwelling. Phlebotomines exhibited diversified food
      consumption patterns in relation to carbohydrate sources. They fed on both native
      and exotic species of arboreal and shrubby vegetables and gramineous plants. 

PMID- 24581361
TI  - Entomological surveillance, spatial distribution, and diversity of Culicidae
      (Diptera) immatures in a rural area of the Atlantic Forest biome, State of Sao
      Paulo, Brazil.
AB  - Because of the high adaptive capacity of mosquitoes, studies that focus on
      transitional environments become very important, such as those in rural areas,
      which are considered as bridges between wild diseases and human populations of
      urban areas. In this study, a survey of the existing species of mosquitoes was
      performed in an Atlantic Forest area of the city of Santa Barbara d'Oeste, Sao
      Paulo state, Brazil, using traps for immatures and analyzing the frequency and
      distribution of these insects over the sampling months. Five mosquito species
      were found: Aedes albopictus (the most frequent species), Aedes aegypti, Aedes
      fluviatilis, Culex quinquefasciatus, and Toxorhynchites theobaldi. The 4,524 eggs
      collected in ovitraps showed the presence of the tribe Aedini. Aedes aegypti and
      Ae. albopictus were identified after larval hatching in the laboratory, with
      different spatial distributions: the first of which coincides with the area of
      greatest diversity calculated using the Simpson index, while the second does not.
      The association of ecological analysis of spatial diversity with simple methods
      of data collection enables the identification of possible epidemiological risk
      situations and is a strategy that may be implemented to monitor ecological
      processes resulting from the interaction among different species of mosquitoes. 

PMID- 24581362
TI  - The presence of white eggs in the monitoring of Aedes albopictus ( Diptera:
      Culicidae) by ovitraps.
AB  - Using international trading and passive transportation routes, the Asian tiger
      mosquito, Aedes albopictus (Skuse, 1894), has colonized Europe. While the most
      common tool to monitor the presence of the mosquito is the ovitrap, other kinds
      of eggs are occasionally found in the traps as well. Most of the eggs are easy to
      distinguish, however, some white-yellow eggs have a similar shape and size to
      those of the tiger mosquito and are often falsely identified as freshly laid
      tiger mosquito eggs. We have shown that these eggs had been laid by Psychoda
      alternata Say, 1824, and the misinterpretation may cause large errors in
      calculating density and patterns of Ae. albopictus. To avoid mistakes, a
      microscopic observation should be done at least 48 h after collecting the sample
      to permit Ae. albopictus eggs to darken. 

PMID- 24581363
TI  - The impact of encroachment of mangroves into saltmarshes on saltwater mosquito
      habitats.
AB  - Will mangrove encroachment into saltmarshes affect saltwater mosquito habitats?
      To address this, we synthesized information from two perspectives: 1) at a
      detailed level, the immature mosquito habitat within mangroves; 2) at a more
      general or regional level, changes due to mangrove expansion into saltmarshes.
      This is a synthesis of two research projects. One showed that mosquito larval
      habitats in mangroves are complex, related to the detailed interactions between
      topography and tidal patterns and that not all parts of a mangrove forest are
      suitable habitat. The other, based on remote sensing and analysis of rainfall
      data, showed that mangrove encroachment in eastern Australia is related to both
      climate and human land use over several decades (1972-2004). An important
      question emerged: when mangroves encroach into saltmarshes will they displace
      saltmarsh immature mosquito habitats or will they replace them with mangrove
      ones? There is no simple answer: it will vary with climate change and sea level
      scenario and how these affect the system. We conclude that mosquito management,
      which is locally implemented, needs to be integrated with land use planning
      systems, which often operate at a more general level. 

PMID- 24581364
TI  - Resistance to freezing temperatures in Aedes (Ochlerotatus) albifasciatus
      (Macquart) eggs (Diptera: Culicidae) from two different climatic regions of
      Argentina.
AB  - Aedes (Ochlerotatus) albifasciatus (Macquart) has the capacity to proliferate in
      different kinds of climates within its distribution range in South America. With
      the aim of studying local thermal adaptations of eggs, we exposed egg stocks from
      two climatically different localities: temperate humid pampa (Buenos Aires) and
      cold arid Patagonian (Sarmiento), to freezing conditions and then evaluated the
      effect on some features at this level. First, we thermally described the
      substrate where this species lays its eggs in the arid region. A typical thermal
      condition during winter was 10 h at -12 degrees  C. Second, we evaluated the
      effect of freezing on primary hatching (vs total hatching) and embryo survival.
      We also compared the proportion of embryonated eggs from both populations. The
      proportions of embryonated eggs were not different between localities, with
      averages of 78% and 83% in Sarmiento and Buenos Aires, respectively. Survival was
      equally successful after freezing in the two localities with an average range
      between 94-99%. Whether or not the eggs from Buenos Aires and Sarmiento were
      under freezing conditions, hatching was more than 98% after the first flooding.
      The results suggest that eggs of Ae. albifasciatus from Sarmiento and Buenos
      Aires have the same ability to survive at extreme temperatures (<0 degrees  C),
      showing a regional thermal adaptation rather than a local one. 

PMID- 24581365
TI  - Relationship between temporal abundance of ticks and incidence of Lyme
      borreliosis in Lower Silesia regions of Poland.
AB  - The aim of this study was to identify the factors determining the incidence of
      Lyme borreliosis (LB) in south-western Poland by estimating the prevalence of B.
      burgdorferi s. l. in I. ricinus, and to analyze the temporal abundance of ticks
      in relation to epidemiological data on LB incidence. Host-seeking ticks collected
      in 2011 in four districts in southwestern Poland were examined by nested PCR for
      the presence of B. burgdorferi s.l. In total, 2,507 host-seeking I. ricinus were
      collected. The temporal abundance of ticks varied between districts. The minimal
      infection rates with B. burgdorferi s.l. were 11.5% for nymphs and 37.7% for
      adults. There were no statistical differences in the level of infection between
      districts either for nymphs or for adults. Five different genospecies were
      identified within the B. burgdorferi s.l. complex: B. garinii, B. afzelii, B.
      lusitaniae, B. valasiana, and B. burgdorferi s.s., and additionally B. miyamotoi.
      Our results point to a relationship between tick temporal abundance and LB
      incidence both for adults and nymphs. The high abundance of ticks is positively
      correlated with the number of LB cases in humans. The tick's abundance may be
      considered as a major factor in determining the LB risk in southwestern Poland. 

PMID- 24581366
TI  - Dislodgement effect of natural semiochemicals released by disturbed triatomines:
      a possible alternative monitoring tool.
AB  - The quick detection of domestic and peridomestic triatomines in their
      environments becomes difficult without the use of dislodgement substances that
      flush them out from their shelters. At present, tetramethrin 0.2% is being widely
      used in control programs. Although it is an efficient dislodging agent, its
      toxicity might affect the health of captured triatomines, of other insects and,
      to a lesser extent, of other animals, including humans. Here, we tested if
      semiochemicals released by disturbed adults of Triatoma infestans and/or Rhodnius
      prolixus can make larvae of the same species exit from their refuges. In a
      walking olfactometer we found that: 1) larvae of T. infestans were repelled by
      the odors released by disturbed adults of their own species and of R. prolixus,
      2) larvae of R. prolixus did not change their behavior in the presence of odors
      released by adults of both species, and 3) activity levels were not modulated by
      these odors in any of both species. Besides, in pseudo-natural conditions we
      found an increased flushing-out activity of larvae of T. infestans when their
      shelters were sprayed with isobutyric acid or 3-pentanol, and of larvae of R.
      prolixus when sprayed with 3-methyl-1-butanol. We succeeded in this work to
      dislodge larvae of triatomines from artificial shelters using natural volatile
      compounds, allowing the capture of live bugs for further investigations (e.g.,
      xenodiagnosis or genetic studies) and favoring ecological aspects (e.g.,
      minimizing environmental insecticide-contamination and non-targeted mortality).

PMID- 24581368
TI  - Comparative field study to evaluate the performance of three different traps for
      collecting sand flies in northeastern Italy.
AB  - Three standard methods for collecting sand flies (sticky trap, CDC light trap,
      and CO2 trap) were compared in a field study conducted from June to October,
      2012, at a site located in the center of a newly established autochthonous focus
      of canine leishmaniasis in northeastern Italy. Six traps (two sticky traps, two
      CDC light traps, and two CO2 traps) were activated at the same time for a single
      night every two weeks during the season of sand fly activity. A total of 5,667
      sand flies were collected and 2,213 identified, of which 82.1% were Phlebotomus
      perniciosus, 17.4% P. neglectus, 0.3% Sergentomya minuta, and 0.2% P. mascitti.
      The performances of all traps were influenced by their position inside the site,
      increasing with proximity to the animal shelters. CO2 traps were more attractive
      for females of P. perniciosus and P. neglectus. CDC light traps showed an
      intermediate efficiency and were more attractive for P. neglectus, compared to
      other two traps. Results suggest that in northern Italy the CO2 trap is a
      suitable sampling method for sand fly monitoring programs that include
      transmitted pathogen surveillance. 

PMID- 24581367
TI  - Ixodid ticks associated with feral swine in Texas.
AB  - Ixodid ticks were collected from feral swine in eight Texas ecoregions from 2008
      2011. Sixty-two percent of 806 feral swine were infested with one or more of the
      following species: Amblyomma americanum, A. cajennense, A. maculatum, Dermacentor
      albipictus, D. halli, D. variabilis, and Ixodes scapularis. Juvenile and adult
      feral swine of both sexes were found to serve as host to ixodid ticks.
      Longitudinal surveys of feral swine at four geographic locations show persistent
      year-round tick infestations of all gender-age classes for tick species common to
      their respective geographic locations and ecoregions. Amblyomma americanum, A.
      cajennense, A. maculatum and D. variabilis were collected from 66% of feral swine
      harvested through an abatement program in seven ecoregions from March to October
      in 2009. These results indicate westward geographic expansion of D. variabilis.
      Summary results show feral swine are competent hosts for ixodid species
      responsible for the transmission of pathogens and diminished well-being in
      livestock, wildlife, and humans. 

PMID- 24581369
TI  - Small-stature emergent macrophytes and crepuscular sprinkler disturbance reduce
      mosquito abundance in wetland mesocosms.
AB  - The impact of emergent macrophyte species and crepuscular sprinkler disturbance
      on mosquito abundance over a 2-year period was measured in wetland mesocosms.
      Mosquito oviposition and abundance of immature mosquitoes and aquatic
      invertebrates were monitored in monotypic plots of small-stature (height of
      mature stands <1.5 m) alkali bulrush (Schoenoplectus maritimus) and large-stature
      (height of mature stands > 2 m) California bulrush (Schoenoplectus californicus)
      without or with daily sprinkler showers to deter mosquito egg laying. Relative to
      wetlands without operational sprinklers, oviposition by culicine mosquitoes was
      reduced by > 99% and immature mosquito abundance was reduced by > 90% by
      crepuscular sprinkler applications. Mosquito abundance or distribution in
      wetlands did not differ between the two bulrush species subjected to the
      sprinkler treatment. Alkali bulrush wetlands without daily sprinkler treatments
      contained more egg rafts but significantly fewer mosquito larvae than did
      California bulrush wetlands. Predaceous damselfly naiads were 3-5 times more
      abundant in alkali bulrush than in California bulrush. Stem density, rate of
      spread, and autumnal mortality of alkali bulrush were higher than for California
      bulrush. Replacement of large emergent macrophytes by smaller species may enhance
      the efficacy of integrated mosquito management programs to reduce mosquito
      transmitted disease cycles associated with multipurpose constructed wetlands used
      worldwide for water reclamation and habitat restoration. 

PMID- 24581370
TI  - Crustacean biodiversity as an important factor for mosquito larval control.
AB  - Newly established ponds, which are highly dynamic systems with changing levels of
      biological interactions among species, are common larval mosquito habitats. We
      investigated the impact of crustacean abundance and taxa diversity on mosquito
      oviposition and larval development. The effects of the biological larvicide
      Bacillus thuringiensis israelensis (Bti) on mosquito larvae were monitored
      according to fluctuations in crustacean communities. Populations of the mosquito
      Culex pipiens colonized artificial ponds that contained crustacean communities at
      different time points of colonization by crustaceans: 1) 'no colonization' (no
      crustaceans), 2) 'simultaneous colonization' by crustaceans and mosquitoes, and
      3) 'head-start colonization' by crustaceans (preceding colonization by
      mosquitoes). All types of ponds were treated with three concentrations of Bti
      (10, 100, or 1,000 ug/liter). Colonization of all ponds by Cx. pipiens (in terms
      of oviposition, larval abundance, and larval development) decreased significantly
      with increasing diversity of crustacean taxa. The total abundance of crustaceans
      had a minor effect on colonization by Cx. pipiens. The presence of crustaceans
      increased the sensitivity of Cx. pipiens larvae to Bti treatment by a factor of
      10 and delayed the time of recolonization. This effect of Bti was relevant in the
      short term. In the long term, the presence of Cx. pipiens was determined by
      crustacean biodiversity. 

PMID- 24581371
TI  - Survey of adult Ixodes scapularis Say for disease agents in Mississippi.

PMID- 24581372
TI  - Six polymorphic microsatellites in the flood-water mosquito Aedes sticticus.

PMID- 24581373
TI  - Experimental investigation of a hantavirus host-switch between arvicoline rodents
      Lemmus lemmus and Myodes glareolus.

PMID- 24581374
TI  - Sand fly surveillance and control on Camp Ramadi, Iraq, as part of a
      leishmaniasis control program.

PMID- 24581375
TI  - New records of immature Ixodes brunneus Koch (Acari: Ixodidae) from Mississippi,
      U.S.A.

PMID- 24581378
TI  - Effects of chlorpyrifos on glutathione S-transferase in migratory locust, Locusta
      migratoria.
AB  - Chlorpyrifos is a typical organophosphate pesticide and is among the most widely
      used worldwide. The objective of the present investigation was to assess the
      effect of chlorpyrifos exposure on glutathione S-transferase in Locusta
      migratoria. In the present study, chlorpyrifos (0.1, 0.2, and 0.4mgg(-1) body
      weight) was topically applied in the abdomen of locusts. The GST activity, mRNA
      levels of ten L. migratoria GSTs and protein levels of four representative GSTs
      were detected. The results showed that chlorpyrifos treatment caused significant
      decrease of 1,2-dichloro-4-nitrobenzene (DCNB) and p-nitro-benzyl chloride (p
      NBC) activities, whereas 1-chloro-2,4-dinitrobenzene (CDNB) activity was not
      altered in locusts. The mRNA levels of seven L. migratoria GSTs, including
      LmGSTs2, LmGSTs3, LmGSTs4, LmGSTs5, LmGSTs6, LmGSTt1, and LmGSTu1, were decreased
      after chlorpyrifos exposure. The protein levels of LmGSTs5, LmGSTt1 and LmGSTu1
      were significantly decreased at higher doses of chlorpyrifos. However,
      chlorpyrifos elevated the mRNA and protein expression of LmGSTd1. It indicated
      that LmGSTd1 might contribute to the resistance of locust to organophosphate
      pesticides such as chlorpyrifos, whereas the decrease in other GSTs might be an
      economic compensation by the insect to differentially regulate the expression of
      enzymes involved in the detoxification of insecticides on the expense of those
      that are not. 

PMID- 24581379
TI  - Role of physiological mechanisms and EPSPS gene expression in glyphosate
      resistance in wild soybeans (Glycine soja).
AB  - The physiological mechanisms underlying glyphosate resistance in wild soybean
      germplasm and relevant EPSPS gene expression were evaluated. These germplasms
      were selected by gradually increasing glyphosate selection pressure started from
      2010. As indicated by a whole-plant dose response bioassay, ZYD-254 plants were
      resistant to glyphosate at concentrations of 1230gaeha(-1), but the susceptible
      plants (ZYD-16) were unable to survive in the presence of 300gaeha(-1)
      glyphosate. The ED50 values of resistant germplasm were approximately 8.8 times
      of the susceptible germplasm. Chlorophyll content was significantly decreased in
      ZYD-16 plants in comparison with ZYD-254 plants. ZYD-16 plants accumulated 10.1
      times more shikimate in leaves at 5days after glyphosate treatment at 1230gaeha(
      1) than ZYD-254 did. GST activity differed between ZYD-254 and ZYD-16 in three
      tissues. It was highest in leaves. There were no significant differences in
      EPSPS1 or EPSPS3 expression between two germplasms before exposure to glyphosate
      treatment. After glyphosate treatment, there was a 2- to 4-fold increase in
      EPSPS1 mRNA levels in ZYD-254, but there was no change in EPSPS3 mRNA levels in
      ZYD-254 or ZYD-16. 

PMID- 24581380
TI  - Effect of allyl isothiocyanate on ultra-structure and the activities of four
      enzymes in adult Sitophilus zeamais.
AB  - Rarefaction and vacuolization of the mitochondrial matrix of AITC-treated (allyl
      isothiocyanate-treated) adult Sitophilus zeamais were evident according to the
      ultra-structural by TEM. Four important enzymes in adult S. zeamais were further
      studied after fumigation treatment with allyl isothiocyanate (AITC) extracted
      from Armoracia rusticana roots and shoots. The enzymes were glutathione S
      transferase (GST), catalase (CAT), cytochrome c oxidase, and acetylcholinesterase
      (AChE). The results indicated that the activities of the four enzymes were
      strongly time and dose depended. With prolonged exposure time, treatment with
      0.74MUg/mL AITC inhibited the activities of cytochrome c oxidase, AChE, and CAT,
      but induced the activity of GST. The activities of cytochrome c oxidase, AChE,
      and CAT were remarkably induced at a low AITC dosage (0.25MUg/mL), but were
      restrained with increased AITC dosage. The activity of GST was inhibited at a low
      AITC dosage (0.5MUg/mL), but was induced at a high AITC dosage (1.5MUg/mL).
      According to the results of TEM, toxic symptoms and enzymes activities, it
      suggested that mitochondrial maybe the one site of action of AITC against the
      adult S. zeamais and it also suggested that cytochrome c oxidase maybe one target
      protein of AITC against the adult S. zeamais, which need to further confirmed by
      protein function tested. 

PMID- 24581381
TI  - Antioxidant mediated ameliorative steroidogenesis by Commelina benghalensis L.
      and Cissus quadrangularis L. against quinalphos induced male reproductive
      toxicity.
AB  - Quinalphos (QP) is speculated to cause endocrine disruption through the
      generation of reactive oxygen species (ROS) by oxidative stress (OS). Exposure of
      QP decreased testosterone level considerably which resulted in reduced viable
      sperms in mice. The QP induced toxicity is initiated by the formation of free
      radicals as it is evidenced from the increased Lipid peroxidation (LPO) and
      diminution of antioxidant enzymes in testicular tissue. Increased serum
      cholesterol and reduced testicular cholesterol indicated the inhibition of
      cholesterol transport and biosynthesis in testicular tissues. Lack of cholesterol
      in testicular tissue impaired the steroidogenesis by down-regulating the
      expression of StAR protein, Cytochrome P450, 3beta-HSD and 17beta-HSD leading to
      reduced testosterone level. Treatment of Commelina benganlensis (CBE) and Cissus
      quadrangularis (CQE) significantly recovered the alterations in antioxidant
      profiles as well as increased LPO, thereby recovering the decreased mRNA
      expression levels of intermediate enzymes. However, CQE effectively protected the
      OS and prevented the inhibition of steroidogenesis thereby preventing male
      infertility. 

PMID- 24581382
TI  - The effect of metabolites and impurities of glyphosate on human erythrocytes (in
      vitro).
AB  - The toxicity of herbicides to animals and human is an issue of worldwide concern.
      The present study was undertaken to evaluate toxic potential of widely used
      pesticide - glyphosate, its metabolites: aminomethylphosphonic acid (AMPA);
      methylphosphonic acid and its impurities: N-(phosphonomethyl)iminodiacetic acid
      (PMIDA), N-methylglyphosate, hydroxymethylphosphonic acid and bis
      (phosphonomethyl)amine. We evaluated the effect of those compounds on hemolysis,
      hemoglobin oxidation, reactive oxygen species (ROS) formation and changes in
      morphology of human erythrocytes. The erythrocytes were exposed to different
      concentrations of glyphosate and its metabolites and impurities (0.01-5mM) for 1,
      4 and 24h. Glyphosate, its metabolites and impurities induced a little hemolysis
      and hemoglobin oxidation. All changes were very low, even after 24h incubation.
      Most of the investigated compounds induced reactive oxygen species formation from
      0.25mM, except the N-methylglyphosate which caused an increase in ROS formation
      from 0.5mM. Moreover, the investigated xenobiotics did not change the size and
      shape (except bis-(phosphonomethyl)amine) of the human erythrocytes. Changes in
      human erythrocytes were observed only when high concentrations of the compounds
      were applied. Some investigated metabolites and impurities caused a slight
      stronger damage to human erythrocytes than a glyphosate. The results clearly show
      that the changes induced in the erythrocytes can occur only as a result of
      poisoning with these compounds. 

PMID- 24581383
TI  - Fluensulfone is a nematicide with a mode of action distinct from
      anticholinesterases and macrocyclic lactones.
AB  - Plant parasitic nematodes infest crops and present a threat to food security
      worldwide. Currently available chemical controls e.g. methyl bromide,
      organophosphates and carbamates have an unacceptable level of toxicity to non
      target organisms and are being withdrawn from use. Fluensulfone is a new
      nematicide of the fluoroalkenyl thioether group that has significantly reduced
      environmental impact with low toxicity to non-target insects and mammals. Here,
      we show that the model genetic organism Caenorhabditis elegans is susceptible to
      the irreversible nematicidal effects of fluensulfone. Whilst the dose required is
      higher than that which has nematicidal activity against Meloidogyne spp. the
      profile of effects on motility, egg-hatching and survival is similar to that
      reported for plant parasitic nematodes. C. elegans thus provides a tractable
      experimental paradigm to analyse the effects of fluensulfone on nematode
      behaviour. We find that fluensulfone has pleiotropic actions and inhibits
      development, egg-laying, egg-hatching, feeding and locomotion. In the case of
      feeding and locomotion, an early excitation precedes the gross inhibition. The
      profile of these effects is notably distinct from other classes of anthelmintic
      and nematicide: the inhibition of motility caused by fluensulfone is not
      accompanied by the hypercontraction which is characteristic of organophosphates
      and carbamates and C. elegans mutants that are resistant to the carbamate
      aldicarb and the macrocyclic lactone ivermectin retain susceptibility to
      fluensulfone. These data indicate fluensulfone's mode of action is distinct from
      currently available nematicides and it therefore presents a promising new
      chemical entity for crop protection. 

PMID- 24581384
TI  - Clinico-hematological and tissue changes induced by butachlor in male Japanese
      quail (Coturnix japonica).
AB  - The present experiment was executed to determine the pathological effects induced
      by concurrent feeding of butachlor (chloroacetanilide herbicide) in male Japanese
      quail. For this purpose mature male quail about 4-5weeks of age were procured
      from the local market and randomly divided into six equal groups (A-F). Butachlor
      was mixed in corn oil and administered orally for 30days using crop tube. Four
      birds from each group were killed at day 10, 20 and 30 of the experiment and
      blood was collected with and without anticoagulant. The birds in groups (A-D) did
      not reveal any clinical and behavioral alterations. Clinical signs like watery
      droppings, dullness, ruffled feather, depression, decrease frequency of crowing,
      mounting with pen mates and foam production were observed. Maximum intensity of
      these clinical signs and behavioral alterations were observed in group F
      throughout the experiment. Significant lower values of erythrocytes, hematocrit
      percent and hemoglobin were recorded. Significantly increased numbers of
      erythrocytes with micronuclei, lobed and notched nuclei were observed.
      Histopathologically, enlarged intertubular space, fewer numbers of round
      spermatids, necrotic spermatids and admixture of dead spermatids were observed in
      testes. The results revealed significant increase in serum lactate dehydrogenase
      (LDH), aspartate transaminase (AST), alanine transaminase (ALT) and urea
      concentrations. The results of present experimental study indicated that
      butachlor induces hematobiochemical and testicular changes in birds. 

PMID- 24581385
TI  - Genetics and mechanisms of imidacloprid resistance in house flies.
AB  - Imidacloprid is the most widely used neonicotinoid insecticide against house
      flies, which are major pests at animal production facilities worldwide. However,
      cases of both physiological and behavior resistance have been reported. Recently,
      physiological resistance to imidacloprid was found in the United States
      (California and Florida). However, no studies have been undertaken to
      characterize this resistance in house flies from the United States. Three
      imidacloprid selections of a strain originally collected from Florida increased
      the level of resistance, ultimately resulting in a strain that had 2300-fold
      resistance in females and 130-fold in males. Imidacloprid resistance was not
      overcome with piperonyl butoxide (PBO) suggesting that resistance is not due to
      detoxification by cytochrome P450s. Resistance was mapped to autosomes 3 and 4.
      There was?100-fold cross-resistance to acetamiprid and dinotefuran, but no cross
      resistance to spinosad. The resistance in this imidacloprid selected population
      was unstable and declined over a period of several months. The significance of
      these results to management of imidacloprid resistance in the field, and
      potential mechanisms of resistance involved, are discussed. 

PMID- 24581386
TI  - Cardiac responses to elevated seawater temperature in Atlantic salmon.
AB  - BACKGROUND: Atlantic salmon aquaculture operations in the Northern hemisphere
      experience large seasonal fluctuations in seawater temperature. With summer
      temperatures often peaking around 18-20 degrees C there is growing concern about
      the effects on fish health and performance. Since the heart has a major role in
      the physiological plasticity and acclimation to different thermal conditions in
      fish, we wanted to investigate how three and eight weeks exposure of adult
      Atlantic salmon to 19 degrees C, previously shown to significantly reduce growth
      performance, affected expression of relevant genes and proteins in cardiac
      tissues under experimental conditions. RESULTS: Transcriptional responses in
      cardiac tissues after three and eight weeks exposure to 19 degrees C (compared to
      thermal preference, 14 degrees C) were analyzed with cDNA microarrays and
      validated by expression analysis of selected genes and proteins using real-time
      qPCR and immunofluorescence microscopy. Up-regulation of heat shock proteins and
      cell signaling genes may indicate involvement of the unfolded protein response in
      long-term acclimation to elevated temperature. Increased immunofluorescence
      staining of inducible nitric oxide synthase in spongy and compact myocardium as
      well as increased staining of vascular endothelial growth factor in epicardium
      could reflect induced vascularization and vasodilation, possibly related to
      increased oxygen demand. Increased staining of collagen I in the compact
      myocardium of 19 degrees C fish may be indicative of a remodeling of connective
      tissue with long-term warm acclimation. Finally, higher abundance of transcripts
      for genes involved in innate cellular immunity and lower abundance of transcripts
      for humoral immune components implied altered immune competence in response to
      elevated temperature. CONCLUSIONS: Long-term exposure of Atlantic salmon to 19
      degrees C resulted in cardiac gene and protein expression changes indicating that
      the unfolded protein response, vascularization, remodeling of connective tissue
      and altered innate immune responses were part of the cardiac acclimation or
      response to elevated temperature.

PMID- 24581387
TI  - A novel therapeutic approach in pulmonary arterial hypertension as a complication
      of adult-onset Still's disease: targeting IL-6.
AB  - Adult-onset Still's Disease (AOSD), often though as the adult variant of systemic
      juvenile idiopathic arthritis (JIA), has an incidence of 1-3 cases per 1 million.
      Cardinal manifestations include fever, arthritis, skin rash, sore throat,
      hepatosplenomegaly and lymphadenopathy. Prolongation in diagnosing this disease
      results from its similarity to infectious, malignant and rheumatic diseases and
      lack of biomarkers. Pulmonary arterial hypertension (PAH) is a rare pulmonary
      complication of AOSD, and we are aware of only six cases reported in literature
      to date. Here we present a patient with AOSD who has developed pulmonary
      hypertension as a complication. We report a case of AOSD complicated by PAH
      treated successfully with tocilizumab, a humanized monoclonal antibody to human
      interleukin (IL)-6 receptor. A Pubmed and Medline search for evidence of
      pulmonary hypertension in AOSD and use of IL-6 inhibition in management was
      performed. Data for this study was collected from the patient's chart records. No
      infectious or neoplastic cause of her disease was identified and after extensive
      diagnostic workup, the patient was diagnosed with AOSD fulfilling Yamaguchi
      criteria. After initiation of IL-6 therapy the patient was followed over time to
      monitor the hemodynamic changes in pulmonary vasculature. Following treatment
      with Tocilizumab, the patient showed dramatic improvement in her clinical
      symptoms and remains in remission, through combination of tocilizumab (8 mg/kg),
      methotrexate and prednisone. Improvement of systemic symptoms, right heart
      catheterization (RHC) findings and the VECTRA-DA score served as a measure of
      treatment response. Tocilizumab has been effective in demonstrating marked
      improvement in both the clinical and laboratory parameters. Tocilizumab is an
      effective novel treatment for AOSD with PAH. This is the first documented report
      of successful use of tocilizumab in AOSD patients presenting with PAH.
      Prospective comparative studies could help validate its efficacy and safety.

PMID- 24581388
TI  - The tools for virulence of Cryptococcus neoformans.
AB  - Cryptococcus neoformans is a fungal pathogen that causes almost half a million
      deaths each year. It is believed that most humans are infected with C.
      neoformans, possibly in a form that survives through latency in the lung and can
      reactivate to cause disease if the host becomes immunosuppressed. C. neoformans
      has a remarkably sophisticated intracellular survival capacities yet it is a free
      living fungus with no requirement for mammalian virulence whatsoever. In this
      review, we discuss the tools that C. neoformans possesses to achieve survival,
      latency and virulence within its host. Some of these tools are mechanisms to
      withstand starvation and others aim to protect against microbicidal molecules
      produced by the immune system. Furthermore, we discuss how these tools were
      acquired through evolutionary pressures and perhaps accidental stochastic events,
      all of which combined to produce an organism with an unusual and unique
      intracellular pathogenic strategy. 

PMID- 24581389
TI  - Community interactions of oral streptococci.
AB  - It is now clear that the most common oral diseases, dental caries and
      periodontitis, are caused by mixed-species communities rather than by individual
      pathogens working in isolation. Oral streptococci are central to these disease
      processes since they are frequently the first microorganisms to colonize oral
      surfaces and they are numerically the dominant microorganisms in the human mouth.
      Numerous interactions between oral streptococci and other bacteria have been
      documented. These are thought to be critical for the development of mixed-species
      oral microbial communities and for the transition from oral health to disease.
      Recent metagenomic studies are beginning to shed light on the co-occurrence
      patterns of streptococci with other oral bacteria. Refinements in microscopy
      techniques and biofilm models are providing detailed insights into the spatial
      distribution of streptococci in oral biofilms. Targeted genetic manipulation is
      increasingly being applied for the analysis of specific genes and networks that
      modulate interspecies interactions. From this work, it is clear that streptococci
      produce a range of extracellular factors that promote their integration into
      mixed-species communities and enable them to form social networks with
      neighboring taxa. These "community integration factors" include coaggregation
      mediating adhesins and receptors, small signaling molecules such as peptides or
      autoinducer-2, bacteriocins, by-products of metabolism including hydrogen
      peroxide and lactic acid, and a range of extracellular enzymes. Here, we provide
      an overview of various types of community interactions between oral streptococci
      and other microorganisms, and we consider the possibilities for the development
      of new technologies to interfere with these interactions to help control oral
      biofilms. 

PMID- 24581390
TI  - Bioprospecting in the genomic age.
AB  - The genomic revolution promises great advances in the search for useful
      biocatalysts. Function-based metagenomic approaches have identified several
      enzymes with properties that make them useful candidates for a variety of
      bioprocesses. As DNA sequencing costs continue to decline, the volume of genomic
      data, along with their corresponding predicted protein sequences, will continue
      to increase dramatically, necessitating new approaches to leverage this
      information for gene-based bioprospecting efforts. Additionally, as new functions
      are discovered and correlated with this sequence information, the knowledge of
      the often complex relationship between a protein's sequence and function will
      improve. This in turn will lead to better gene-based bioprospecting approaches
      and facilitate the tailoring of desired properties through protein engineering
      projects. In this chapter, we discuss a number of recent advances in
      bioprospecting within the context of the genomic age. 

PMID- 24581391
TI  - Environmental and animal-associated enterococci.
AB  - Enterococci are generally commensal bacteria inhabiting the gastrointestinal
      tract of humans and animals. They have, however, been implicated as the
      etiological agent of a variety of illnesses and nosocomial infections. In
      addition to pathogenic potential, there is growing concern regarding the
      incidence of antibiotic resistance and genetic exchange among Enterococcus spp.
      within and among a variety of animal hosts. While primarily considered an enteric
      group, extra-enteric habitats in which enterococci persist and potentially grow
      have been studied for decades. Although many biotic (e.g., predation) and abiotic
      (e.g., sunlight, nutrients, and salinity) stressors have been thought to limit
      the success of enterococci in these secondary habitats, a growing body of
      evidence suggests that certain strains may become naturalized to environmental
      habitats. Enterococci have also been used for decades as indicators of fecal
      contamination in recreational waters where increased concentrations of this group
      have been linked to the incidence of illness in humans following recreational use
      of these waters. Persistence of enterococci in secondary habitats, however,
      suggests that their presence in ambient waters may prove to be a poor indicator
      of actual risks to public health. In this chapter, we provide a review of the
      existing body of literature concerning animal host associations, genetic exchange
      is reviewed, and emphasis is placed on the growing body of evidence for the
      persistence and growth of enterococci in secondary habitats. 

PMID- 24581392
TI  - An introduction to nitric oxide sensing and response in bacteria.
AB  - Nitric oxide (NO) is a radical gas that has been intensively studied for its role
      as a bacteriostatic agent. NO reacts in complex ways with biological molecules,
      especially metal centers and other radicals, to generate other bioactive
      compounds that inhibit enzymes, oxidize macromolecules, and arrest bacterial
      growth. Bacteria encounter not only NO derived from the host during infection but
      also NO derived from other bacteria and inorganic sources. The transcriptional
      responses used by bacteria to respond to NO are diverse but usually involve an
      iron-containing transcription factor that binds NO and alters its affinity for
      either DNA or factors involved in transcription, leading to the production of
      enzymatic tolerance systems. Some of these systems, such as flavohemoglobin and
      flavorubredoxin, directly remove NO. Some do not but are still important for NO
      tolerance through other mechanisms. The targets of NO that are protected by these
      systems include many metabolic pathways such as the tricarboxylic acid cycle and
      branched chain amino acid synthesis. This chapter discusses these topics and
      others and serves as a general introduction to microbial NO biology. 

PMID- 24581393
TI  - Brachytherapy boost in loco-regionally advanced nasopharyngeal carcinoma: a
      prospective randomized trial of the International Atomic Energy Agency.
AB  - BACKGROUND: The purpose was to determine whether a brachytherapy boost improves
      outcomes in patients with advanced nasopharyngeal carcinoma treated with standard
      chemo-radiotherapy. METHODS: Patients with nasopharyngeal carcinoma WHO grades I
      III and TNM stages III or non-metastatic stage IV were eligible for this phase
      III study. Patients were randomized to either arm (A) induction chemotherapy,
      followed by external beam radiotherapy (EBRT) with concomitant cisplatin (n =
      139) or arm (B), the same schedule plus a brachytherapy boost to the nasopharynx
      (n = 135). The EBRT doses given were 70 Gy to the primary tumour and positive
      lymph nodes and 46 Gy to the negative neck. The additional brachytherapy boost in
      arm (B) was given by either low dose-rate (LDR - 11 Gy) or high dose-rate (HDR -
      3 fractions of 3.0 Gy) brachytherapy. The primary endpoint was 3-year overall
      survival (OS) and secondary endpoints were: local control, regional control,
      distant metastasis and grade 3-4 adverse events. RESULTS: 274 patients were
      randomized between September 2004 and December 2008. The two arms were comparable
      with regard to age, gender, stage and grade. 273 patients completed treatment.
      Median follow-up was 29 months (0.2-67 months). The effect of treatment arm,
      country, age, gender, WHO pathology, stage (T3-4, N2-3 versus other) and
      chemotherapy on overall survival (OS), disease-free survival (DFS) and local
      recurrence-free survival (LRFS) was studied. Stage significantly affected OS (p =
      0.024) and DFS (p = 0.018) while age significantly affected OS (p = 0.014). None
      of the other factors studied were significant. The 3-year LRFS was 60.5% and
      54.4% in arms A and B respectively (p = 0.647). The 3-year regional control rate
      in the neck was 59.7% and 54.3% respectively (p = 0.7). Distant metastasis
      developed in 59.7% of patients in arm A and 55.4% in arm B (p = 0.377). Patients
      with T1/T2 N + had a 3 year LRFS of 51.8% in Arm A (62 patients) versus 57.9% in
      Arm B (67 patients) (p = 0.343). The grade 3-4 toxicity rate was 21.6% (30/139)
      and 24.4% (33/135) respectively (p = 0.687). CONCLUSIONS: The addition of a
      brachytherapy boost to external beam radiotherapy and chemotherapy did not
      improve outcome in loco-regionally advanced nasopharyngeal carcinoma.

PMID- 24581396
TI  - Quantifying function: status critical.

PMID- 24581395
TI  - Limitations of cadaveric organ donation on judicial cases and problems confronted
      in autopsy: Istanbul data in comparative perspective.
AB  - Organ transplantation is one of the most important services of modern medicine to
      the humanity. In judicial death cases the interaction between judicial needs and
      transplantation needs is inevitable and both should be provided in a short time
      before the decomposition of the body. Thus, the description of this interaction
      and the algorithm which should be carried out to manage these cases are
      important. Aim of this study is to determine the problems confronted in forensic
      autopsies and to determine what to do for both judicial processes' and cadaveric
      organ donations' not becoming limited due to each other. With these aims, autopsy
      case archive of the Council of Forensic Medicine Istanbul Morgue Department was
      reviewed, between the years 2009 and 2011, to reveal the number of organ donors
      among autopsy cases and also to find out the judicial problems confronted during
      autopsies. Among 12,016 judicial death cases referred to Istanbul Morgue
      Department in 3 years, 35 cases were found to have undergone cadaveric solid
      organ harvesting procedure and 307 cases cornea-only harvesting procedure. Manner
      of deaths for organ donor cases were blunt trauma due to traffic accident in 20
      cases, firearm injury in 3 cases, stabbing in 2 cases, suspicious criminal
      battery in 4 cases and fatal falls in 5 cases. Only 1 case was suspected to have
      died due to high dose insulin administration. Through the whole data presented in
      this study, it can be concluded that consulting with the Forensic Medicine Expert
      not only for the autopsies but also during the clinical process of a judicial
      case, who is a candidate to be an organ donor, is absolutely important. The early
      contribution of the Forensic Medicine Expert would provide help to plan both the
      judicial process and the transplantation process which needs urgent decisions. A
      Forensic Medicine Expert may be an organ harvest team member performing initial
      investigations on the cause of death and collecting some of the toxicological
      screening samples when needed. 

PMID- 24581394
TI  - Impact of long-lasting, insecticidal nets on anaemia and prevalence of Plasmodium
      falciparum among children under five years in areas with highly resistant malaria
      vectors.
AB  - BACKGROUND: The widespread use of insecticide-treated nets (LLINs) leads to the
      development of vector resistance to insecticide. This resistance can reduce the
      effectiveness of LLIN-based interventions and perhaps reverse progress in
      reducing malaria morbidity. To prevent such difficulty, it is important to know
      the real impact of resistance in the effectiveness of mosquito nets. Therefore,
      an assessment of LLIN efficacy was conducted in malaria prevention among children
      in high and low resistance areas. METHODS: The study was conducted in four rural
      districts and included 32 villages categorized as low or high resistance areas in
      Plateau Department, south-western Benin. Larvae collection was conducted to
      measure vector susceptibility to deltamethrin and knockdown resistance (kdr)
      frequency. In each resistance area, around 500 children were selected to measure
      the prevalence of malaria infection as well as the prevalence of anaemia
      associated with the use of LLINs. RESULTS: Observed mortalities of Anopheles
      gambiae s.s population exposed to deltamethrin ranged from 19 to 96%. Knockdown
      resistance frequency was between 38 and 84%. The prevalence of malaria infection
      in children under five years was 22.4% (19.9-25.1). This prevalence was 17.3%
      (14.2-20.9) in areas of high resistance and 27.1% (23.5-31.1) in areas of low
      resistance (p=0.04). Eight on ten children that were aged six - 30 months against
      seven on ten of those aged 31-59 months were anaemic. The anaemia observed in the
      six to 30-month old children was significantly higher than in the 31-59 month old
      children (p=0.00) but no difference associated with resistance areas was observed
      (p=0.35). The net use rate was 71%. The risk of having malaria was significantly
      reduced (p<0.05) with LLIN use in both low and high resistance areas. The
      preventive effect of LLINs in high resistance areas was 60% (95% CI: 40-70), and
      was significantly higher than that observed in low resistance areas (p<0.05).
      CONCLUSION: The results of this study showed that the resistance of malaria
      vectors seems to date not have affected the impact of LLINs and the use of LLINs
      was highly associated with reduced malaria prevalence irrespective of resistance.

PMID- 24581397
TI  - Elevating the quality of disability and rehabilitation research: mandatory use of
      the reporting guidelines.
AB  - Note from the AJOT Editor-in-Chief: Since 2010, the American Journal of
      Occupational Therapy (AJOT) has adopted reporting standards based on the
      Consolidated Standards of Reporting Trials (CONSORT) Statement and American
      Psychological Association (APA) guidelines in an effort to publish transparent
      clinical research that can be easily evaluated for methodological and analytical
      rigor (APA Publications and Communications Board Working Group on Journal Article
      Reporting Standards, 2008; Moher, Schulz, & Altman, 2001). AJOT has now joined 28
      other major rehabilitation and disability journals in a collaborative initiative
      to enhance clinical research reporting standards through adoption of the EQUATOR
      Network reporting guidelines, described below. Authors will now be required to
      use these guidelines in the preparation of manuscripts that will be submitted to
      AJOT. Reviewers will also use these guidelines to evaluate the quality and rigor
      of all AJOT submissions. By adopting these standards we hope to further enhance
      the quality and clinical applicability of articles to our readers. 

PMID- 24581398
TI  - Habilitative services: an essential health benefit and an opportunity for
      occupational therapy practitioners and consumers.

PMID- 24581400
TI  - Difficulty in mental, neuromusculoskeletal, and movement-related school functions
      associated with low birthweight or preterm birth: a meta-analysis.
AB  - OBJECTIVE. Our objective was to perform a meta-analysis to investigate whether
      low birthweight (LBW) or preterm birth was associated with difficulty in mental,
      neuromusculoskeletal, and movement-related school function tasks. METHOD. Two
      search strategies produced 40 studies that met the inclusion criteria for the
      meta-analysis and yielded 549 effect sizes (d). Heterogeneity was evaluated by
      obtaining Q and I-squared values. Egger's regression intercept test and a funnel
      plot were used to check for publication bias. RESULTS. Children born LBW
      exhibited considerable difficulties in mental (d = -0.655, p < .0001) and
      neuromusculoskeletal and movement-related tasks (d = -0.391, p < .0001) compared
      with children of normal birthweight. Children born preterm also exhibited
      significant difficulties compared with full-term children in mental,
      neuromusculoskeletal, and movement-related tasks (d = -0.237, p < .0001).
      CONCLUSION. Deficits in mental and motor functions in children born LBW or
      preterm appear to have significant effects on school readiness and academic
      achievement. 

PMID- 24581401
TI  - Effects of weighted vests on attention, impulse control, and on-task behavior in
      children with attention deficit hyperactivity disorder.
AB  - OBJECTIVE. In this study, we examined the effectiveness of using weighted vests
      for improving attention, impulse control, and on-task behavior in children with
      attention deficit hyperactivity disorder (ADHD). METHOD. In a randomized, two
      period crossover design, 110 children with ADHD were measured using the Conners'
      Continuous Performance Test-II (CPT-II) task. RESULTS. In the weighted vest
      condition, the participants did show significant improvement in all three
      attentional variables of the CPT-II task, including inattention; speed of
      processing and responding; consistency of executive management; and three of four
      on-task behaviors, including off task, out of seat, and fidgets. No significant
      improvements in impulse control and automatic vocalizations were found.
      CONCLUSION. Although wearing a weighted vest is not a cure-all strategy, our
      findings support the use of the weighted vest to remedy attentional and on-task
      behavioral problems of children with ADHD. 

PMID- 24581402
TI  - Potential predictors of functional outcomes after home-based constraint-induced
      therapy for children with cerebral palsy.
AB  - OBJECTIVE. Our objective was to identify predictors for treatment outcomes after
      home-based constraint-induced therapy (CIT) in children with cerebral palsy (CP).
      METHOD. Forty-three children (aged 4-12 yr) with CP were treated with
      individualized CIT at home for 4 wk. Potential predictors were age, sex, affected
      hand, and upper-extremity motor capacity measured by the Peabody Developmental
      Motor Scale, 2nd edition (PDMS-2). Outcomes were the Pediatric Motor Activity Log
      (PMAL) Amount of Hand Use and Quality of Hand Use subscales and the Functional
      Independence Measure for Children (WeeFIM). RESULTS. A higher PDMS-2 Visual-Motor
      Integration subscale score predicted a better WeeFIM score after home-based CIT
      (adjusted R2 = .35). Younger age predicted better performance on the PMAL Amount
      of Hand Use and Quality of Hand Use subscales (adjusted R2 = .06-.08) after home
      based CIT. CONCLUSION. The potential predictors may allow occupational therapy
      practitioners to target those children who will benefit most after home-based
      constraint-induced therapy. 

PMID- 24581404
TI  - Activity participation among children with autism spectrum disorder.
AB  - OBJECTIVE. The purpose of this study was to empirically derive dimensions of
      activity participation among a sample of school-age children with autism spectrum
      disorder (ASD; n = 713). Additionally, we examined the associations between
      dimensions of activity participation and child characteristics (i.e.,
      chronological age, autism severity, gender) and family demographics (i.e.,
      maternal education). METHOD. Exploratory factor analysis was used to determine
      the factors on the Home and Community Activities Scale (HCAS). Multiple
      regression was used to examine the extent to which child characteristics and
      family demographics were related to HCAS dimensions. RESULTS. A six-factor model
      best characterized activity participation among the school-age children with ASD,
      and child characteristics and family demographics were differentially associated
      with HCAS dimensions. CONCLUSION. The findings have implications for how
      activities may be categorized for children with ASD and suggest that the
      frequency of specific activities is affected by child characteristics and
      maternal education. 

PMID- 24581405
TI  - Responsiveness of the Manual Ability Measure-36 (MAM-36): changes in hand
      function using self-reported and clinician-rated assessments.
AB  - OBJECTIVE. To examine the responsiveness of the Manual Ability Measure-36 (MAM
      36) compared with a clinician-administered functional assessment. METHOD. The MAM
      36 was administered to 46 patients (Cohort A, n = 20; Cohort B, n = 26) with
      various upper-extremity conditions. All patients received occupational therapy
      intervention for 2-37 wk and were retested at discharge. Additionally, the Smith
      Hand Function Test (SHFT), including task performance speeds and grip strength
      measurements, was administered to Cohort B at intake and discharge. RESULTS.
      Manual ability improved significantly at discharge in all patients. Patients also
      showed significant improvement on the SHFT. The correlation between gain in MAM
      36 and gain in grip strength was moderate. The standardized response mean for the
      MAM-36 was 1.18. CONCLUSION. The MAM-36 was responsive to changes in hand
      function in patients receiving occupational therapy services. MAM-36 results
      correlated positively with improvements in task performance speeds and grip
      strength. 

PMID- 24581403
TI  - School function in students with Down syndrome.
AB  - People with Down syndrome (DS) are predisposed to specific areas of relative
      developmental strength and challenge, but it is unclear whether and how this
      profile affects participation in school and community settings. In this study we
      characterized the nature of school participation and performance of functional
      tasks in the school context for 26 elementary students with DS (mean age = 7.86
      yr; standard deviation = 1.75). Students participated in assessments of cognitive
      status and language development. Their teachers completed the School Function
      Assessment (Coster, Deeney, Haltiwanger, & Haley, 1998) questionnaire and a
      standardized questionnaire on executive functioning (EF). Students demonstrated a
      pronounced pattern of assistance- and adaptation-related needs across various
      domains of school function. The strongest predictor of school function was EF
      skills, as reported by teachers (adjusted R2 = .47, p = .003). Findings from this
      study should inform future intervention and school-related planning for
      elementary school students with DS. 

PMID- 24581406
TI  - Effects of partnerships between people with mobility challenges and service dogs.
AB  - OBJECTIVE. The purpose of this study was to examine the effects of partnerships
      between people with disabilities and service dogs on functional performance and
      social interaction. METHOD. A single-subject, alternating treatment design was
      used. The participants were 3 women with mobility challenges who owned service
      dogs. For each participant, time and perceived amount of effort for two tasks
      were measured for functional performance. Interaction and satisfaction levels
      were measured for social interactions. RESULTS. Primary findings were that
      service dog partnerships decreased performance time for four of the six tasks,
      decreased effort for five of the six tasks, increased social interactions for 2
      of the participants, and increased levels of satisfaction with social
      interactions for all participants. CONCLUSION. For adult women with mobility
      challenges, service dog partnerships may contribute to energy conservation
      through decreased time and effort required to complete some tasks and may
      increase social interactions. 

PMID- 24581408
TI  - Addressing everyday challenges: feasibility of a family caregiver training
      program for people with dementia.
AB  - OBJECTIVE. The purpose of this study was to examine the feasibility and efficacy
      of the Family Caregiver Training Program for assisting with the basic activities
      of daily living of people with dementia. METHOD. A one-group pretest-posttest
      research design with a 3-mo follow-up was used to examine the efficacy of a
      manualized education program for caregivers. The 6-hr training was delivered to
      72 family caregivers over 3 consecutive weeks (2 hr/wk) by trained clinicians.
      RESULTS. Caregivers showed a significant gain in knowledge of how to effectively
      assist with communication and nutrition, t(52) = 7.05, p < .000; transfers and
      toileting, t(45) = 3.10, p < .003; and bathing and dressing, t(44) = 2.71, p <
      .01, of their care recipients. CONCLUSION. Our findings demonstrate that this
      manualized intervention protocol is a promising method of equipping family
      members with the skills needed to face their everyday challenges in caring for
      people with dementia. 

PMID- 24581407
TI  - Single-case design evaluation of compression therapy for edema of the stroke
      affected hand.
AB  - OBJECTIVE. To explore the efficacy of low- and high-stretch compression bandaging
      for edema management in the stroke-affected upper limb. METHOD. A single-case,
      ABA-design study was conducted with 8 participants alternately allocated to
      receive low- or high-stretch bandaging. Edema was measured with circumferential
      tape at four specified points from the hand to the mid-forearm. All measurements
      were represented graphically for visual analysis, and celeration lines were
      calculated to indicate the degree of slope in each phase. RESULTS. Visual
      analysis indicated fluctuating edema volume in the first baseline phase,
      decreasing edema volume in the intervention phase, and increasing edema volume in
      the second baseline phase. The results did not clearly distinguish between the
      two bandaging groups. CONCLUSION. Compression bandaging may have benefits in the
      management of edema after stroke. Further research is required to identify
      factors contributing to the long-term maintenance of reductions gained after
      compression bandaging. 

PMID- 24581410
TI  - Effects of object size on unimanual and bimanual movements in patients with
      schizophrenia.
AB  - Schizophrenia affects not only mental function but also movement. We compared the
      movement of patients with mild schizophrenia and healthy control participants
      during a bimanual assembly task and examined whether changes in object size
      affected unimanual and bimanual movements. Fifteen patients with schizophrenia
      and 15 age- and gender-matched control participants were instructed to bimanually
      reach for and assemble objects. We manipulated the object size for the left hand
      (large vs. small) and measured movement time, peak velocity, and bimanual
      synchronization to represent movement speed, forcefulness, and bimanual
      coordination. Patients with schizophrenia showed slower and less forceful
      unimanual movements and less coordinated bimanual movements than control
      participants. Increasing the object size elicited faster and more forceful
      unimanual movements and more coordinated bimanual movements in patients. The
      results suggest the need for movement rehabilitation in patients with
      schizophrenia and the possibility of manipulating object size to optimize
      patients' movements. These results benefit the practice of evidence-based
      therapy. 

PMID- 24581409
TI  - Predicting road test performance in drivers with stroke.
AB  - OBJECTIVE. The aim of this study was to develop a brief screening battery to
      predict the on-road performance of drivers who had experienced a stroke. METHOD.
      We examined 72 people with stroke referred by community physicians to an academic
      rehabilitation center. The outcome variable was pass or fail on the modified
      Washington University Road Test. Predictor measures were tests of visual, motor,
      and cognitive functioning. RESULTS. The best predictive model for failure on the
      road test included Trail Making Test Part A and the Snellgrove Maze Task((r)).
      CONCLUSION. A screening battery that can be performed in less than 5 min was able
      to assist in the prediction of road test performance in a sample of drivers with
      stroke. A probability of failure calculator may be useful for clinicians in their
      decision to refer clients with stroke for a comprehensive driving evaluation. 

PMID- 24581411
TI  - Research opportunities in the area of children and adolescents with challenges in
      sensory processing and sensory integration.
AB  - The American Occupational Therapy Association (AOTA) Evidence-Based Practice
      Project has developed a table summarizing the research opportunities on children
      and adolescents with challenges in sensory processing and sensory integration.
      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 Evidence-Based Practice Guidelines Series.
      Researchers, students, and clinicians can use this information in developing
      innovative research to answer important questions within the occupational therapy
      field. American Occupational Therapy Association. (2014). Research opportunities
      in the area of children and adolescents with challenges in sensory processing and
      sensory integration. 

PMID- 24581412
TI  - Relationship between play and sensory processing: a systematic review.
AB  - OBJECTIVE. We examined the empirical evidence to answer the research question,
      What is the relationship between play and sensory processing in children ages 3
      12 yr? METHOD. The PRISMA guidelines were followed to complete a systematic
      review. Academic databases were searched using play, leisure, sensory processing,
      and sensory integration as primary search terms. Of 6,230 articles initially
      identified, 35 full-text articles were screened for eligibility. Of these, 8 met
      the inclusion criteria. RESULTS. All 8 studies were conducted within the United
      States. The evidence of the relationship between play and sensory processing fell
      mainly into the low levels of evidence: case studies and cohort studies.
      CONCLUSION. This review provides occupational therapists with an emerging
      understanding of the relationship between play and sensory processing based on
      current evidence and its importance in the occupational development of children.
      Rigorous research is needed in the area. 

PMID- 24581413
TI  - Comparison of occupational therapy students' perceived skills after traditional
      and nontraditional fieldwork.
AB  - We studied students' perceptions regarding their professional and personal skills
      and compared the findings for those who completed community fieldwork (CF) with
      those completing traditional fieldwork (TF). We also compared the perceptions of
      CF students whose placement settings had an active occupational therapist present
      versus those whose settings did not. Results showed no significant differences in
      perceptions of professional and personal skills between the students involved in
      CF and those involved in TF. However, students who completed CF in a setting
      without an active occupational therapist present scored significantly higher in
      their perception of their personal responsibility, cultural competence, and
      overall personal skills than students whose fieldwork location had an active
      occupational therapist present. Our study indicates the value of using various
      supervisory strategies for occupational therapy students during fieldwork.
      Further studies are warranted. 

PMID- 24581414
TI  - The professional occupational therapy doctoral degree: why do it?
AB  - This article presents a rationale for the development of professional
      occupational therapy doctorate (OTD) programs. As more universities transition to
      the entry-level OTD degree, opportunities are becoming available to advance the
      profession and increase benefits to clients. We analyzed the current health care
      environment and developed the following proposed outcomes for doctoral-trained
      practitioners: (1) Demonstrate advanced clinical skills; (2) attain proficiency
      in outcomes measurement and analysis and synthesis of outcomes data; (3)
      routinely use standardized evidence-based practice clinical guidelines that
      translate research into practice; (4) develop, implement, and lead health
      promotion services; and (5) excel as partners in interprofessional teams. 

PMID- 24581417
TI  - Comparison of two different measurement methods to determine glenoid bone
      defects: area or width?
AB  - BACKGROUND: This study compared two different techniques that have been used to
      measure the glenoids of patients with recurrent anterior shoulder dislocation.
      METHODS: We analyzed 36 patients who had received arthroscopic Bankart repair for
      anterior shoulder instability. Retrospectively, 3-dimensional computed tomography
      images of both shoulders were available for these patients. Two measurement
      methods were compared to determine the glenoid defects. One of these techniques
      is based on linear measurement, previously defined as the glenoid index. The
      other method is based on surface area measurement. Subsequently, 3 more diameters
      and the average values obtained from these diameters were compared with the
      surface measurement method. Pearson correlation coefficient (r) was assessed to
      determine the relationship. RESULTS: There was an almost perfect relationship
      between measurement methods when the defect area was less than 6% of the inferior
      glenoid circle (r, 0.915; P < .001). This relation decreased and the difference
      became more pronounced (r, 0.343; P = .657) when the bone loss exceeded 14% of
      the inferior glenoid circle. The highest correlations with the actual defects
      were the average values obtained from 4 different diameters (r, 0.964; P < .001)
      and the 4-o'clock position of the single diameter measurements (r, 0.860; P =
      .001). In addition, 11 patients had crescent-like defects, demonstrating a
      relatively low correlation between the measurement methods (r, 0.679; P = .021).
      CONCLUSION: Although the best correlation was achieved from average values
      obtained from different diameter positions, in practical use, we advise a linear
      measurement to estimate the glenoid bone loss at the 4-o'clock position to
      achieve a high correlation between the measurement techniques.

PMID- 24581415
TI  - Review of occupational therapy intervention research in the practice area of
      children and youth 2009-2013.
AB  - PURPOSE. We conducted a systematic review examining the extent to which pediatric
      intervention research recently published in the American Journal of Occupational
      Therapy reflects occupational therapy's holistic occupation-based tenets. METHOD.
      We surveyed 10 systematic reviews and analyzed 38 single effectiveness studies
      for intervention approach, type, level of environmental targeting, level of
      occupational task and participation practice, and measures used. RESULTS. Of the
      38 single effectiveness studies, 12 (32%) explicitly incorporated both
      environmental targets of intervention and practice of complex or in vivo
      occupational tasks, with steady increases during the 2009-2013 time frame.
      CONCLUSION. In the area of children and youth, occupational therapy is making
      steady gains in reflecting and demonstrating the effectiveness of the
      profession's holistic, occupation-based tenets. Occupational therapy researchers
      must be mindful to ensure that despite the reductionist nature of intervention
      research, interventions reflect the profession's holistic understanding of the
      interplay between the child, environment, and occupations. 

PMID- 24581418
TI  - Patient adherence with postoperative restrictions after rotator cuff repair.
AB  - HYPOTHESIS: This study aimed to measure self-reported patient adherence to
      postoperative restrictions after rotator cuff repair, to evaluate correlations
      between adherence and functional outcome, and to identify possible indicators of
      poor adherence. We believed that poor adherence would correlate with poor
      functional outcome. METHODS: Fifty consecutive patients undergoing repair for
      rotator cuff tears were included and instructed to wear an abduction brace for 6
      weeks after surgery. Functional evaluations, including American Shoulder and
      Elbow Surgeons score, University of California-Los Angeles shoulder score, and
      Simple Shoulder Test, were made preoperatively and postoperatively. Patients
      commented on their adherence with a medical adherence measurement questionnaire.
      RESULTS: Average adherence was 88% (range, 59.2-100). There were no significant
      correlations between adherence and improvement in American Shoulder and Elbow
      Surgeons, University of California-Los Angeles, or Simple Shoulder Test scores
      after rotator cuff repair (P = .06245, .5891, and .7688). Of the patient
      demographics analyzed, only smoking status had a positive effect on adherence (P
      = .00432; coefficient, 9.867). All other demographics, including hand dominance,
      mechanism of injury, repair complexity, comorbidities, living status, employment
      status, and age, had no significant effect on self-measured adherence to
      postoperative restrictions (P = .7876, .5889, .6444, .4190, .0609, .4171, .5402).
      CONCLUSIONS: Patients' self-reported adherence did not correlate with shoulder
      outcome as measured on any of 3 functional outcome scores.

PMID- 24581420
TI  - Cancer pain in America: missing the target of relieving suffering.

PMID- 24581421
TI  - Neurotech report.

PMID- 24581422
TI  - Current science.

PMID- 24581419
TI  - Atypical antipsychotics and hyperglycemic emergencies: multicentre, retrospective
      cohort study of administrative data.
AB  - OBJECTIVE: To evaluate the relationship between initiation of atypical
      antipsychotic agents and the risk of hyperglycemic emergencies. METHOD: We
      conducted a multicentre retrospective cohort study using administrative health
      data from 7 Canadian provinces and the UK Clinical Practice Research Datalink.
      Hospitalizations for hyperglycemic emergencies (hyperglycemia, diabetic
      ketoacidosis, hyperosmolar hyperglycemic state) were compared between new users
      of risperidone (reference), and new users of olanzapine, other atypical
      antipsychotics, and typical antipsychotics. We used propensity scores with
      inverse probability of treatment weighting and proportional hazard models to
      estimate the site-specific hazard ratios of hyperglycemic emergencies in the year
      following drug initiation separately for adults under and over age 66 years. Site
      level results were pooled using meta-analytic methods. RESULTS: Among 725,489
      patients, 55% were aged 66+years; 5% of younger and 19% of older patients had pre
      existing diabetes. Hyperglycemic emergencies were rare (1-2 per 1000 person
      years), but more frequent in patients with pre-existing diabetes (6-12 per 1000
      person years). We did not find a significant difference in risk of hyperglycemic
      emergencies with initiation of olanzapine versus risperidone; however
      heterogeneity existed between sites. The risk of an event was significantly lower
      with other atypical (99% quetiapine) compared to risperidone use in older
      patients [adjusted hazard ratio, 95% confidence interval (CI): 0.69, 0.53-0.90].
      CONCLUSIONS: Risk for hyperglycemic emergencies is low after initiation of
      antipsychotics, but patients with pre-existing diabetes may be at greater risk.
      The risk appeared lower with the use of quetiapine in older patients, but the
      clinical significance of the findings requires further study.

PMID- 24581423
TI  - Physician response to medtronic's position on the use of off-label medications in
      the synchromed pump.

PMID- 24581426
TI  - Establishment and directed differentiation of induced pluripotent stem cells from
      glycogen storage disease type Ib patient.
AB  - Glycogen storage disease type Ib (GSDIb) is caused by a deficiency in the glucose
      6-phosphate transporter (G6PT), which leads to neutrophil dysfunction. However,
      the underlying causes of these dysfunctions and their relationship with glucose
      homeostasis are unclear. Induced pluripotent stem cells (iPSCs) hold a great
      promise for advances in developmental biology, cell-based therapy and modeling of
      human disease. Here, we examined the use of iPSCs as a model for GSDIb. In this
      study, one 2-year-old patient was genetically screened and diagnosed with GSDIb.
      We established iPSCs and differentiated these cells into hepatocytes and
      neutrophils, which comprise the main pathological components of GSDIb. Cells that
      differentiated into hepatocytes exhibited characteristic albumin secretion and
      indocyanine green uptake. Moreover, iPSC-derived cells generated from patients
      with GSDIb metabolic abnormalities recapitulated key pathological features of the
      diseases affecting the patients from whom they were derived, such as glycogen,
      lactate, pyruvate and lipid accumulation. Cells that were differentiated into
      neutrophils also showed the GSDIb pathology. In addition to the expression of
      neutrophil markers, we showed increased superoxide anion production, increased
      annexin V binding and activation of caspase-3 and caspase-9, consistent with the
      GSDIb patient's neutrophils. These results indicate valuable tools for the
      analysis of this pathology and the development of future treatments. 

PMID- 24581425
TI  - Cytohesin-2 phosphorylation by protein kinase C relieves the constitutive
      suppression of platelet dense granule secretion by ADP-ribosylation factor 6.
AB  - BACKGROUND: Protein kinase C (PKC) is a major regulator of platelet function and
      secretion. The underlying molecular pathway from PKC to secretion, however, is
      poorly understood. By a proteomics screen we identified the guanine nucleotide
      exchange factor cytohesin-2 as a candidate PKC substrate. OBJECTIVES: We aimed to
      validate cytohesin-2 as a PKC substrate in platelets and to determine its role in
      granule secretion and other platelet responses. METHODS AND RESULTS:
      Immunoprecipitation was performed with a phosphoserine PKC substrate antibody
      followed by mass spectrometry, leading to the identification of cytohesin-2. By
      western blotting we showed that different agonists induced cytohesin-2
      phosphorylation by PKC. Protein function was investigated using a pharmacological
      approach. The cytohesin inhibitor SecinH3 significantly enhanced platelet dense
      granule secretion and aggregation, as measured by lumi-aggregometry. Flow
      cytometry data indicate that alpha-granule release and integrin alphaII b beta3
      activation were not affected by cytohesin-2 inhibition. Lysosome secretion was
      assessed by a colorimetric assay and was also unchanged. As shown by western
      blotting, ARF6 interacted with cytohesin-2 and was present in an active GTP-bound
      form under basal conditions. Upon platelet stimulation, this interaction was
      largely lost and ARF6 activation decreased, both of which could be rescued by PKC
      inhibition. CONCLUSIONS: Cytohesin-2 constitutively suppresses platelet dense
      granule secretion and aggregation by keeping ARF6 in a GTP-bound state. PKC
      mediated phosphorylation of cytohesin-2 relieves this inhibitory effect, thereby
      promoting platelet secretion and aggregation.

PMID- 24581427
TI  - High glucose improves healing of periodontal wound by inhibiting proliferation
      and osteogenetic differentiation of human PDL cells.
AB  - Periodontal ligament (PDL) cells play an important role in wound healing of
      periodontal tissues. Response of PDL cells' cellular activity to high-glucose
      concentration levels may be the key in understanding the relationship between
      periodontal disease and diabetes mellitus. We studied the effect of high-glucose
      medium on proliferation of PDL cells in vitro. PDL cells were cultured for 1, 4,
      7, 10, 14 and 17 days in normal (1100 mg/l) glucose or in high (4500 mg/l)
      glucose medium. The 3-(4,5-dimethylithiazol-2-yl)-2,5-diphenyl tetrazolium
      bromide (MTT) assay for proliferation was performed. In order to evaluate the
      osteogenetic differentiation of human PDL cells, the cells were induced with
      normal- or high-glucose medium for 1, 7, 14, 21 and 28 days. The results
      indicated that high glucose significantly inhibited proliferation of PDL cells.
      Concerning the mineralised nodule formation, the percentage of calcified area to
      total culture dish of PDL cells in high glucose level was lower than that in
      normal glucose medium. The increase in alkaline phosphatase activity and collagen
      expression could be observed in high-glucose-containing osteogenetic factor. In
      conclusion, high glucose improves healing of periodontal wound by inhibiting
      proliferation and differentiation of PDL cells, which could explain for delayed
      periodontal regeneration and healing in diabetic patients. 

PMID- 24581428
TI  - Immunotherapy: what lies beyond.
AB  - Allergen immunotherapy has been used to treat allergic diseases, such as asthma,
      allergic rhinitis, and venom allergy, since first described over a century ago.
      The current standard of care in the United States involves subcutaneous
      administration of clinically relevant allergens for several months, building up
      to eventual monthly injections for typically 3 to 5 years. Recent advances have
      improved the safety and efficacy of immunotherapy. The addition of omalizumab or
      Toll-like receptor agonists to standard subcutaneous immunotherapy has proved
      beneficial. Altering the extract itself, either through chemical manipulation
      producing allergoids or directly producing recombinant proteins or significant
      peptides, has been evaluated with promising results. The use of different
      administration techniques, such as sublingual immunotherapy, is common in Europe
      and is on the immediate horizon in the United States. Other methods of
      administering allergen immunotherapy have been studied, including epicutaneous,
      intralymphatic, intranasal, and oral immunotherapy. In this review we focus on
      new types and routes of immunotherapy, exploring recent human clinical trial
      data. The promise of better immunotherapies appears closer than ever before, but
      much work is still needed to develop novel immunotherapies that induce
      immunologic tolerance and enhanced clinical efficacy and safety over that noted
      for subcutaneous allergen immunotherapy. 

PMID- 24581429
TI  - Mechanisms of allergen-specific immunotherapy: multiple suppressor factors at
      work in immune tolerance to allergens.
AB  - Allergen-specific immunotherapy (AIT) has been used for more than 100 years as a
      desensitizing therapy for IgE-mediated allergic diseases and represents a
      potentially curative way of treatment. The mechanisms of action of AIT include
      the induction of very early desensitization of mast cells and basophils;
      generation of regulatory T and regulatory B (Breg) cell responses; regulation of
      IgE and IgG4; decreases in numbers and activity of eosinophils and mast cells in
      mucosal allergic tissues; and decreases in the activity of basophils in
      circulation. Skewing of allergen-specific effector T and effector B cells to a
      regulatory phenotype appears as a key event in the course of AIT and normal
      immune response to allergens. Recently, inducible IL-10-secreting Breg cells were
      also demonstrated to contribute to allergen tolerance through suppression of
      effector T cells and selective induction of IgG4 isotype antibodies. Allergen
      specific regulatory T and Breg cells orchestrate a general immunoregulatory
      activity, which can be summarized as suppression of cytokines from inflammatory
      dendritic cells; suppression of effector TH1, TH2, and TH17 cells; suppression of
      allergen-specific IgE and induction of IgG4; and suppression of migration of mast
      cells, basophils, eosinophils, and effector T cells to tissues. A detailed
      knowledge of the mechanisms of AIT is not only important in designing the
      prevention and treatment of allergic diseases but might also find applications in
      the treatment of autoimmune diseases, organ transplantation, chronic infection,
      and cancer. 

PMID- 24581432
TI  - Use of omalizumab to improve desensitization safety in allergen immunotherapy.

PMID- 24581434
TI  - Were medicine quality and pharmaceutical management contributing factors in
      diminishing artemisinin efficacy in Guyana and Suriname?
AB  - BACKGROUND: Recent studies in Guyana and Suriname unveiled diminished efficacy of
      artemisinin derivatives based on day-3 parasitaemia. The migrant characteristics
      of the population at risk and the potential development of resistance pose a
      serious health threat in the region. Assessment of factors that may have
      contributed to this situation is warranted, and analysis of the data generated in
      those countries on quality and pharmaceutical managements of anti-malarials may
      contribute to a better understanding of this occurrence. METHODS: Data on malaria
      medicine quality and pharmaceutical management, generated in the context of the
      Amazon Malaria Initiative (AMI), was reviewed and discussed. RESULTS: Numerous
      substandard artemisinin-containing malaria medicines were identified in both
      countries, particularly in Guyana, where a larger number and variety of anti
      malarials were sampled. Poor quality was more frequent in the private and
      informal sector than in the public sector, posing a greater threat to the
      populations at risk, which are mostly located in hard to reach areas with scarce
      public facilities. Stock-outs identified in the public sector in Guyana could
      enhance the need to access those alternative sectors, exacerbating the risk of
      utilizing poor quality medicines. The availability of monotherapies and other non
      recommended therapies for Plasmodium falciparum malaria, could also have
      contributed to the diminished efficacy. The type of quality deficiencies
      identified -reduced content of active pharmaceutical ingredient (API) and/or poor
      dissolution- and the irrational use of non-recommended treatments could result in
      non-sustained or lower levels of API in blood, favouring survival of more
      resistant mutants by exposing parasites to sub-lethal doses of the active
      ingredient. CONCLUSIONS: The quality of malaria medicines and the availability
      and use of non-recommended treatments could have played a role in the diminished
      efficacy of artemisinin derivatives described in Guyana and Suriname. However,
      also other factors need to be considered and a more comprehensive and extensive
      assessment on quality and pharmaceutical management is necessary to establish a
      tighter cause-effect correlation. Nevertheless, relevant authorities in these and
      neighbouring countries should take into consideration the reviewed data to
      properly address the problem when implementing corrective actions.

PMID- 24581435
TI  - In vitro synthesis of proteins in bacterial extracts.
AB  - This protocol describes the methods used to generate protein in a cell-free
      system derived from E. coli. The in vitro synthesis of protein has been used in
      studying many ribosome-based gene regulation steps (Gong and Yanofsky, 2001).
      Such techniques have also been used to study protein-protein, protein-DNA, and
      protein-RNA interactions, and to produce radiolabeled protein species. More
      recently, such approaches have been utilized to produce large quantities of toxic
      proteins for proteomic and structural studies (Yokoyama et al., 2000). 

PMID- 24581430
TI  - Advances in pediatric asthma in 2013: coordinating asthma care.
AB  - Last year's "Advances in pediatric asthma: moving toward asthma prevention"
      concluded that "We are well on our way to creating a pathway around wellness in
      asthma care and also to utilize new tools to predict the risk for asthma and take
      steps to not only prevent asthma exacerbations but also to prevent the early
      manifestations of the disease and thus prevent its evolution to severe asthma."
      This year's summary will focus on recent advances in pediatric asthma on prenatal
      and postnatal factors altering the natural history of asthma, assessment of
      asthma control, and new insights regarding potential therapeutic targets for
      altering the course of asthma in children, as indicated in Journal of Allergy and
      Clinical Immunology publications in 2013 and early 2014. Recent reports continue
      to shed light on methods to understand factors that influence the course of
      asthma, methods to assess and communicate levels of control, and new targets for
      intervention, as well as new immunomodulators. It will now be important to
      carefully assess risk factors for the development of asthma, as well as the risk
      for asthma exacerbations, and to improve the way we communicate this information
      in the health care system. This will allow parents, primary care physicians,
      specialists, and provider systems to more effectively intervene in altering the
      course of asthma and to further reduce asthma morbidity and mortality. 

PMID- 24581436
TI  - Preparation of a Saccharomyces cerevisiae cell-free extract for in vitro
      translation.
AB  - Eukaryotic cell-free in vitro translation systems have been in use since the
      1970s. These systems can faithfully synthesize polypeptides when programmed with
      mRNA, enabling the production of polypeptides for analysis as well as permitting
      analyses of the cis- and trans-acting factors that regulate translation. Here we
      describe the preparation and use of cell-free translation systems from the yeast
      Saccharomyces cerevisiae. 

PMID- 24581437
TI  - Yeast two-hybrid screen.
AB  - Yeast two-hybrid is a method for screening large numbers of gene products
      (encoded by cDNA libraries) for their ability to interact with a protein of
      interest. This system can also be used for characterizing and manipulating
      candidate protein: protein interactions. Interactions between proteins are
      monitored by the growth of yeast plated on selective media. 

PMID- 24581438
TI  - UV cross-linking of interacting RNA and protein in cultured cells.
AB  - RNA-protein interactions play indispensable roles in the regulation of cellular
      functions. Biochemical characterization of these complexes is often done by
      immunoprecipitation (IP) of RNA-binding proteins (RBPs) followed by
      identification of co-immunoprecipitated RNAs. This protocol couples ultraviolet
      (UV) irradiation with IP to determine whether a specific protein interacts
      directly with a specific RNA in living cells. 

PMID- 24581439
TI  - Analysis of RNA-protein interactions by cell mixing.
AB  - RNA-protein complexes are critical for almost all aspects of gene expression.
      Analysis of RNA-protein interactions can be complicated by the disruption of
      native complexes and the formation of new, reassorted complexes upon cell lysis.
      Before concluding that a specific RNA and protein interact in vivo, cell-mixing
      experiments can be performed to ensure that observed RNA-protein complexes are
      not formed after lysis of cells. 

PMID- 24581440
TI  - General protein-protein cross-linking.
AB  - This protocol describes a general protein-to-protein cross-linking procedure
      using the water-soluble amine-reactive homobifunctional BS(3)
      (bis[sulfosuccinimidyl] suberate); however, the protocol can be easily adapted
      using other cross-linkers of similar properties. BS(3) is composed of two sulfo
      NHS ester groups and an 11.4 A linker. Sulfo-NHS ester groups react with primary
      amines in slightly alkaline conditions (pH 7.2-8.5) and yield stable amide bonds.
      The reaction releases N-hydroxysuccinimide (see an application of NHS esters on
      Labeling a protein with fluorophores using NHS ester derivitization).

PMID- 24581441
TI  - Chromatin immunoprecipitation and multiplex sequencing (ChIP-Seq) to identify
      global transcription factor binding sites in the nematode Caenorhabditis elegans.
AB  - The global identification of transcription factor (TF) binding sites is a
      critical step in the elucidation of the functional elements of the genome.
      Several methods have been developed that map TF binding in human cells, yeast,
      and other model organisms. These methods make use of chromatin
      immunoprecipitation, or ChIP, and take advantage of the fact that formaldehyde
      fixation of living cells can be used to cross-link DNA sequences to the TFs that
      bind them in vivo. In ChIP, the cross-linked TF-DNA complexes are sheared by
      sonication, size fractionated, and incubated with antibody specific to the TF of
      interest to generate a library of TF-bound DNA sequences. ChIP-chip was the first
      technology developed to globally identify TF-bound DNA sequences and involves
      subsequent hybridization of the ChIP DNA to oligonucleotide microarrays. However,
      ChIP-chip proved to be costly, labor-intensive, and limited by the fixed number
      of probes available on the microarray chip. ChIP-Seq combines ChIP with massively
      parallel high-throughput sequencing (see Explanatory Chapter: Next Generation
      Sequencing) and has demonstrated vast improvement over ChIP-chip with respect to
      time and cost, signal-to-noise ratio, and resolution. In particular, multiplex
      sequencing can be used to achieve a higher throughput in ChIP-Seq analyses
      involving organisms with genomes of lower complexity than that of human
      (Lefrancois et al., 2009) and thereby reduce the cost and amount of time needed
      for each result. The multiplex ChIP-Seq method described in this section has been
      developed for Caenorhabditis elegans, but is easily adaptable for other
      organisms. 

PMID- 24581443
TI  - Determining the RNA specificity and targets of RNA-binding proteins using a three
      hybrid system.
AB  - The three-hybrid system can be used to identify RNA sequences that bind a
      specific protein by screening a hybrid RNA library with a protein-activation
      domain fusion as 'bait.' These screens complement biochemical techniques, for
      example, SELEX, co-immunoprecipitation, and cross-linking experiments (see UV
      crosslinking of interacting RNA and protein in cultured cells and PAR-CLIP
      (Photoactivatable Ribonucleoside-Enhanced Crosslinking and Immunoprecipitation):
      a step-by-step protocol to the transcriptome-wide identification of binding sites
      of RNA-binding proteins). 

PMID- 24581442
TI  - PAR-CLIP (Photoactivatable Ribonucleoside-Enhanced Crosslinking and
      Immunoprecipitation): a step-by-step protocol to the transcriptome-wide
      identification of binding sites of RNA-binding proteins.
AB  - We recently developed a protocol for the transcriptome-wide isolation of RNA
      recognition elements readily applicable to any protein or ribonucleoprotein
      complex directly contacting RNA (including RNA helicases, polymerases, or
      nucleases) expressed in cell culture models either naturally or ectopically
      (Hafner et al., 2010). Briefly, immunoprecipitation of the RNA-binding protein of
      interest is followed by isolation of the crosslinked and coimmunoprecipitated
      RNA. In the course of lysate preparation and immunoprecipitation, the mRNAs are
      partially degraded using Ribonuclease T1. The isolated crosslinked RNA fragments
      are converted into a cDNA library and deep-sequenced using Solexa technology (see
      Explanatory Chapter: Next Generation Sequencing). By introducing photoreactive
      nucleosides that generate characteristic sequence changes upon crosslinking (see
      below), our protocol allows one to separate RNA segments bound by the protein of
      interest from the background un-crosslinked RNAs. 

PMID- 24581444
TI  - Dissecting a known RNA-protein interaction using a yeast three-hybrid system.
AB  - The yeast three-hybrid system has been applied to known protein-RNA interactions
      for a variety of purposes. For instance, protein and RNA mutants with altered or
      relaxed binding specificities can be identified. Mutant RNAs can also be analyzed
      to better understand RNA-binding specificity of a specific protein. Furthermore,
      this system complements other biochemical techniques, for example, SELEX, co
      immunoprecipitation and cross-linking experiments (see UV crosslinking of
      interacting RNA and protein in cultured cells and PAR-CLIP (Photoactivatable
      Ribonucleoside-Enhanced Crosslinking and Immunoprecipitation): a step-by-step
      protocol to the transcriptome-wide identification of binding sites of RNA-binding
      proteins). 

PMID- 24581445
TI  - Identifying proteins that bind a known RNA sequence using the yeast three-hybrid
      system.
AB  - The yeast three-hybrid system can be used to identify a protein partner of a
      known RNA sequence by screening a cDNA library fused to a transcription
      activation domain, with a hybrid RNA as 'bait.' Most commonly, such screens are
      performed to identify proteins that interact with a given RNA in vivo. 

PMID- 24581446
TI  - Methods in Enzymology. Laboratory methods in enzymology: protein part B. Preface.

PMID- 24581447
TI  - Stapes fixation accompanied with abnormal facial nerve pathway.
AB  - The patient was a 52-year-old woman. She had been aware of her bilateral hearing
      loss since she was 20 years old. The hearing in her left ear started to
      deteriorate at the age of 49. Pure-tone audiometry showed a bilateral mixed
      hearing loss. The hearing levels for the right ear and the left ear were 52 dB
      and 68 dB, respectively. There were no remarkable findings in a computed
      tomography (CT) scan of the temporal bone. We suspected that she had
      otosclerosis, and an operation was performed on her left ear. When the
      incudostapedial joint (I-S joint) was exposed to investigate the movement of the
      stapes, a soft white band that ran under the superstructure of the stapes was
      noted. By using a nerve monitoring system, we confirmed that the white band was
      the bare facial nerve. The ossicular chain was normal, except for a malformed
      stape due to the facial nerve, and the footplate of the stapes was fixed.
      Therefore, she was diagnosed as having otosclerosis with an abnormal facial nerve
      pathway. The malformed superstructure of the stapes was removed carefully. When
      the ectopic facial nerve was shifted to anteroinferior side, the oval window
      could be seen. Stapedotomy using a Teflon piston prosthesis was performed with no
      complications.

PMID- 24581448
TI  - Serum homocysteine levels are decreased in levothyroxine-treated women with
      autoimmune thyroiditis.
AB  - BACKGROUND: Hyperhomocysteinemia is a well-known cardiovascular risk factor and
      its elevation is established in overt hypothyroidism. Since some authors suggest
      that chronic autoimmune thyroiditis per se may be considered as a novel risk
      factor of atherosclerosis independent of thyroid function, the analysis of
      classical cardiovascular risk factors might be helpful in evaluation the
      causative relationship. Data concerning the impact of thyroid autoimmunity in
      euthyroid state on homocysteine (Hcy) level is lacking. The aim of this study was
      to evaluate Hcy level in context of anti-thyroperoxidase antibodies (TPOAbs) in
      euthyroidism. METHODS: It is a case-control study. 31 euthyroid women treated
      with levothyroxine (L-T4) due to Hashimoto thyroiditis (HT) and 26 females in
      euthyroidism without L-T4 replacement therapy were enrolled in the study. All
      women with HT had positive TPOAbs. Forty healthy females negative for TPOAbs
      comparable for age and body mass index (BMI) participated in the study as
      controls. Exclusion criteria were a history of any acute or chronic disease, use
      of any medications (including oral contraceptives and vitamin supplements),
      smoking, alcoholism. RESULTS: TPOAbs titers were higher in both groups of HT
      patients versus the healthy controls. Hcy levels were found to be significantly
      lower in treated HT patients (Me 11 MUmol; IQR 4.2 MUmol) as compared with
      healthy controls (Me 13.35 MUmol; IQR 6.34 MUmol; p = 0.0179). In contrast, no
      significant difference was found between non treated HT and control group in Hcy
      level. The study groups and the controls did not differ in age and BMI.
      Furthermore, levels of TSH, FT4, TC, LDL, HDL and TAG did not differ between the
      study group and the control group. CONCLUSION: The main finding of the study is a
      decrease in Hcy level in treated HT as compared with healthy controls. Based on
      our observations one can also assume that correct L-T4 replacement was associated
      here with a decrease of Hcy. Furthermore, it seems that non treated HT in
      euthyroidism is not associated with Hcy increase, in contrast to overt
      hypothyroidism. This may be just another argument against the concepts about the
      role of "euthyroid HT" in the development of atherosclerosis.

PMID- 24581449
TI  - Role of tRNA modifications in human diseases.
AB  - Transfer RNAs (tRNAs) are key for efficient and accurate protein translation. To
      be fully active, tRNAs need to be heavily modified post-transcriptionally.
      Growing evidence indicates that tRNA modifications and the enzymes catalyzing
      such modifications may play important roles in complex human pathologies. Here,
      we have compiled current knowledge that directly link tRNA modifications to human
      diseases such as cancer, type 2 diabetes (T2D), neurological disorders, and
      mitochondrial-linked disorders. The molecular mechanisms behind these connections
      remain, for the most part, unknown. As we progress towards the understanding of
      the roles played by hypomodified tRNAs in human disease, novel areas of
      therapeutic intervention may be discovered. 

PMID- 24581450
TI  - Why have clinical trials in sepsis failed?
AB  - The systemic inflammatory response is biologically complex, redundant, and
      activated by both infectious and noninfectious triggers. Its manipulation can
      cause both benefit and harm. More than 100 randomized clinical trials have tested
      the hypothesis that modulating the septic response to infection can improve
      survival. With one short-lived exception, none of these has resulted in new
      treatments. The current challenge for sepsis research lies in a failure of
      concept and reluctance to abandon a demonstrably ineffectual research model.
      Future success will necessitate large studies of clinical and biochemical
      epidemiology to understand the course of illness, better integration of basic and
      clinical science, and the creation of stratification systems to target treatment
      towards those who are most likely to benefit. 

PMID- 24581451
TI  - Unmet needs in the treatment of schizophrenia: new targets to help different
      symptom domains.
AB  - Current treatments for schizophrenia, although effective for positive symptoms,
      have not proven as effective for negative symptoms and cognitive dysfunction.
      Additional strategies, such as combining antipsychotics or adding adjunctive
      agents to antipsychotics, have also yielded disappointing results in both
      negative and cognitive symptom domains. However, the N-methyl-d-aspartate (NMDA)
      receptor hypofunction hypothesis, with its focus on the glutamate system's effect
      on dopamine, can explain the positive, negative, and cognitive symptoms in
      schizophrenia. Therapeutic targets are being explored that focus on NMDA
      receptors (eg, glycine, d-serine), glycine reuptake inhibition (such as sarcosine
      and bitopertin), and, through a different pathway, alpha-7 nicotinic
      acetylcholine receptor agonism (eg, encenicline). 

PMID- 24581452
TI  - Developing concepts in negative symptoms: primary vs secondary and apathy vs
      expression.
AB  - Negative symptoms in schizophrenia, such as blunted affect, alogia, asociality,
      anhedonia, and avolition, remain challenging to treat in many patients, but new
      concepts may lead to a better understanding of the definition and treatment of
      these symptoms. The most widely used rating scales for negative symptoms (the
      Scale for the Assessment of Negative Symptoms and the Positive and Negative
      Syndrome Scale) were developed in the 1980s, but more recent findings, such as
      insight into aspects of anhedonia, have led to the creation of new rating scales
      (the Clinical Assessment Interview for Negative Symptoms and the Brief Negative
      Symptom Scale). Clinicians should differentiate between primary and secondary
      negative symptoms in order to select the best treatment option. Secondary
      negative symptoms may be caused by comorbid conditions, psychotic symptoms,
      medication side effects, and substance abuse. On most rating scales, negative
      symptoms have also been found to load onto 1 of 2 domains,
      apathy/anhedonia/asociality or diminished expression (blunted affect and alogia).
      This distinction may facilitate the development of new treatments. 

PMID- 24581453
TI  - Measurements of response, remission, and recovery in schizophrenia and examples
      for their clinical application.
AB  - Different definitions of response, remission, and recovery are used in
      schizophrenia research, which makes comparing and applying results in clinical
      practice difficult. Response criteria are often based on reductions in rating
      scale scores (eg, >= 20% reduction from baseline). However, when reduction scores
      from rating scales, such as the Positive and Negative Syndrome Scale (PANSS) and
      Brief Psychiatric Rating Scale (BPRS), are linked to Clinical Global Impressions
      (CGI) scores, which are more easily understood, rating scale scores have better
      clinical application. This linking process also reveals that the widely used
      response cutoff of 20% does not reflect clinically meaningful improvement in
      patients with acute, nonrefractory schizophrenia. This article provides
      suggestions for selecting response criteria, displaying responder rates, and
      using standard definitions (eg, remission, recovery) in research studies. The
      ultimate goal of recovery in schizophrenia treatment includes sustained symptom
      resolution and a return to full functioning. 

PMID- 24581454
TI  - Disability in schizophrenia: contributing factors and validated assessments.
AB  - Patients with schizophrenia experience impairments in multiple domains of
      everyday life, including the ability to maintain social relationships, sustain
      employment, and live independently. These impairments typically persist after
      patients achieve symptom remission. Assessment of patients' functioning requires
      multiple information sources (such as the patient, a relative, or a case worker)
      and performance-based measures. Functional milestones (for example, marriage or a
      job) are not highly related to each other and require separate assessments.
      Clinicians could enhance their practice by being familiar with assessment tools,
      such as the University of California, San Diego, Performance-Based Skills
      Assessment (UPSA) and the MATRICS Consensus Cognitive Battery, which are designed
      to evaluate real-life skills and cognitive abilities. Although often considered
      together, cognitive and negative symptoms appear to have differential effects on
      domains of functioning and likely require separate treatment interventions. With
      targeted therapies and frequent contact with supportive clinicians, there is
      increasing evidence that patients can improve in their functioning in crucial
      areas that impact their quality of life. 

PMID- 24581457
TI  - Radiofrequency ablation for ground-glass opacity-dominant lung adenocarcinoma.
AB  - PURPOSE: To evaluate retrospectively the clinical utility of lung radiofrequency
      (RF) ablation for the treatment of ground-glass opacity (GGO)-dominant lung
      adenocarcinoma. MATERIALS AND METHODS: From August 2004 through May 2012, 33
      consecutive patients (14 men and 19 women; mean age, 71.1 y; age range, 46-84 y)
      with 42 lung tumors having >= 50% GGO component received lung RF ablation. The
      mean maximum tumor diameter was 1.6 cm +/- 0.9 (range, 0.7-4.0 cm). Feasibility,
      safety, local tumor progression, and survival were evaluated. RESULTS: For the 42
      RF sessions, after RF electrodes were placed in each target tumor, planned
      ablation protocols were completed in all sessions (100%; 42 of 42). No deaths
      related to the RF procedure occurred. Major and minor complication rates were
      4.8% and 23.8%, respectively. Local tumor progression developed in 6 tumors
      (14.3%; 6 of 42) during a mean follow-up of 42 months +/- 23 (range, 5-92 mo).
      Four of six tumors with local progression were controlled by repeated RF
      ablation. No evidence of disease was achieved in 31 of 33 patients (93.9%) at the
      end of the follow-up period. All but one patient (who died of brain hemorrhage)
      are alive today. Overall and cancer-specific survival rates were 100% and 100% at
      1 year, 96.4% (95% confidence interval [CI], 77.5%-99.5%) and 100% at 3 years,
      and 96.4% (95% CI, 77.5%-99.5%) and 100% at 5 years, respectively. CONCLUSIONS:
      Lung RF ablation is a feasible, safe, and useful therapeutic option to control
      GGO-dominant lung adenocarcinoma.

PMID- 24581458
TI  - CT-guided transthoracic needle aspiration biopsy of subsolid lung lesions.
AB  - PURPOSE: To assess the diagnostic performance of computed tomography (CT)-guided
      transthoracic needle aspiration biopsy (TNAB) in the evaluation of persistent
      subsolid lung lesions. MATERIALS AND METHODS: A retrospective review of all CT
      guided TNABs performed at a single institution from January 2002 to November 2012
      was conducted to identify patients with persistent subsolid lung lesions. The
      diagnostic performance of CT-guided TNAB was assessed through comparison of
      cytologic diagnoses with core needle biopsy, surgical resection, or imaging and
      clinical follow-up. The cytologic, histologic, and imaging features of each
      lesion were characterized, and CT-guided TNAB complications were recorded.
      RESULTS: In 32 patients, a diagnosis of benign or malignant disease was
      identified through evaluation of pathologic or follow-up data. There were 18 men
      and 14 women, with a mean age of 67.1 years +/- 9.6 (range, 52-86 y). The mean
      lesion diameter was 21 mm +/- 11 (range, 8-62 mm). A final diagnosis of
      malignancy was made in 28 cases (87.5%); four benign lesions were also diagnosed.
      The overall sensitivity of CT-guided TNAB in the evaluation of these lesions was
      89.2%, and the specificity and positive predictive value were 100%. Two
      pneumothoraces (6.3%) were identified. CONCLUSIONS: Among patients with subsolid
      lung lesions, CT-guided TNAB is safe and shows high sensitivity. The high
      specificity and positive predictive value of the procedure allow for definitive
      treatment decisions to be made for most patients.

PMID- 24581456
TI  - Dynamics of chromatin accessibility and gene regulation by MADS-domain
      transcription factors in flower development.
AB  - BACKGROUND: Development of eukaryotic organisms is controlled by transcription
      factors that trigger specific and global changes in gene expression programs. In
      plants, MADS-domain transcription factors act as master regulators of
      developmental switches and organ specification. However, the mechanisms by which
      these factors dynamically regulate the expression of their target genes at
      different developmental stages are still poorly understood. RESULTS: We
      characterized the relationship of chromatin accessibility, gene expression, and
      DNA binding of two MADS-domain proteins at different stages of Arabidopsis flower
      development. Dynamic changes in APETALA1 and SEPALLATA3 DNA binding correlated
      with changes in gene expression, and many of the target genes could be associated
      with the developmental stage in which they are transcriptionally controlled. We
      also observe dynamic changes in chromatin accessibility during flower
      development. Remarkably, DNA binding of APETALA1 and SEPALLATA3 is largely
      independent of the accessibility status of their binding regions and it can
      precede increases in DNA accessibility. These results suggest that APETALA1 and
      SEPALLATA3 may modulate chromatin accessibility, thereby facilitating access of
      other transcriptional regulators to their target genes. CONCLUSIONS: Our findings
      indicate that different homeotic factors regulate partly overlapping, yet also
      distinctive sets of target genes in a partly stage-specific fashion. By combining
      the information from DNA-binding and gene expression data, we are able to propose
      models of stage-specific regulatory interactions, thereby addressing dynamics of
      regulatory networks throughout flower development. Furthermore, MADS-domain TFs
      may regulate gene expression by alternative strategies, one of which is
      modulation of chromatin accessibility.

PMID- 24581459
TI  - CT volumetric assessment of pulmonary neoplasms after radiofrequency ablation:
      when to consider a second intervention?
AB  - PURPOSE: To determine the minimal follow-up time point to predict therapeutic
      response to radiofrequency (RF) ablation of lung tumors. MATERIALS AND METHODS: A
      retrospective study design was approved by the institutional review board. From
      January 2008 to January 2010, 78 patients (46 men and 32 women; mean age, 58.9 y)
      underwent computed tomography (CT)-guided percutaneous RF ablation of pulmonary
      malignancies. A single RF multitined electrode was used to treat 100 index
      tumors, 6 primary lesions, and 94 metastatic lesions. CT volumetric measurements
      of ablated tumors were made before ablation and 24 hours, 3-6 weeks, 3 months, 6
      months, 9 months, and 12 months after ablation. An unpaired t test and Spearman
      rank correlation coefficient were used to analyze the volumetric changes.
      RESULTS: Complete successful ablation was achieved in 80% of index tumors. The
      mean time to detection of tumor residue or recurrence tumor residue or recurrence
      was 6.7 months after ablation. In successfully ablated lesions, the mean volume
      before ablation was 1.81 cm(3) (standard deviation [SD], 1.71); in failed
      ablation lesions, the mean volume before ablation was 2.58 cm(3) (SD, 2.8) (P =
      .42). The earliest statistically significant follow-up time point that showed a
      difference in the volumetric measurements of failed and successful ablations as
      well as the earliest significant correlation with the 12-month point was 3 months
      (P = .025, Spearman R = 0.72). Secondary tumor control after repeat ablation was
      statistically significant for lesions ablated at a 3-month interval (four out of
      five lesions) (P = .04). CONCLUSIONS: CT volumetric assessment of ablated tumors
      revealed that 3 months was the earliest time point that may determine the
      response of a pulmonary ablation or repeat intervention.

PMID- 24581460
TI  - Portal-left atrium shunt leading to stroke.

PMID- 24581461
TI  - Transarterial treatment of colorectal cancer liver metastases with irinotecan
      loaded drug-eluting beads: technical recommendations.
AB  - Transcatheter hepatic arterial administration of irinotecan-loaded drug-eluting
      beads (DEBIRI) is used to treat liver-only or liver-dominant metastatic disease
      from colorectal cancer (CRC). Eligibility for DEBIRI should be established in
      each individual patient by a multidisciplinary team based on comprehensive
      clinical, imaging, and laboratory assessment. Standardization of DEBIRI technique
      and protocols would be expected to lead to improved efficacy and safety. The
      present article provides a set of technical recommendations for the use of DEBIRI
      in the treatment of hepatic CRC metastases. 

PMID- 24581462
TI  - Transarterial therapy of hepatocellular carcinoma fed by the right renal capsular
      artery.
AB  - PURPOSE: To evaluate the characteristics of hepatocellular carcinomas (HCCs) fed
      by the right renal capsular artery and to assess the tumor response and
      complications in patients treated with transarterial therapy via the renal
      capsular arteries with or without other extrahepatic arteries and/or intrahepatic
      arteries. MATERIALS AND METHODS: Between March 2006 and May 2012, 24 lesions in
      19 patients were treated by transcatheter arterial chemoembolization (23
      sessions), transcatheter arterial embolization (two sessions), or transcatheter
      arterial infusion (one session), with HCCs fed by the right renal capsular artery
      with or without intrahepatic arteries and/or other collateral arteries. Other
      intrahepatic lesions were concurrently treated if needed. RESULTS: Tumor size
      ranged from 10 mm to 107 mm (mean, 30.5 mm). Of the 24 tumors, 12 were located in
      segment VI, 10 in segment VII, one in the posterior segment, and one in the
      anterior segment after posterior segment resection. Severe complication occurred
      in four patients: liver abscess (n = 2), pleural effusion (n = 1), and duodenal
      ulcer (n = 1). Pleural effusion might be related to chemoembolization via the
      right renal capsular artery. A complete response was obtained in six sessions and
      a partial response in eight; 10 sessions were associated with stable disease and
      two with progressive disease. CONCLUSIONS: Precise renal capsular artery
      knowledge would facilitate successful and safe transarterial therapy for HCCs fed
      by the renal capsular arteries.

PMID- 24581463
TI  - The use of technetium-99m-labeled human serum albumin diethylenetriamine
      pentaacetic acid single-photon emission CT scan in the follow-up of type II
      endoleak treatment.
AB  - An 84-year-old woman presented with persistent type II endoleak with sac
      expansion from 57 mm to 75 mm during 4-year follow-up after endovascular
      abdominal aortic aneurysm repair. The patient underwent transabdominal
      embolization with coils and N-butyl cyanoacrylate/ethiodized oil (Lipiodol;
      Guerbet, Villepinte, France) mixture (2.5 mL). Because of the anticipated
      embolization artifacts on follow-up computed tomography (CT), technetium-99m
      labeled human serum albumin diethylenetriamine pentaacetic acid single-photon
      emission computed tomography ((99m)Tc-HSAD SPECT) was performed before and after
      the intervention. Perigraft accumulation on (99m)Tc-HSAD SPECT corresponding to
      the endoleak disappeared after embolization. CT scan performed 12 months after
      embolization showed no signs of sac expansion. (99m)Tc-HSAD SPECT may be useful
      for evaluating therapeutic effect after embolization for endoleak. 

PMID- 24581464
TI  - Long-term central venous access in pediatric patients at high risk: conventional
      versus antibiotic-impregnated catheters.
AB  - PURPOSE: To study selective use of antibiotic-impregnated catheters in children
      at increased risk of venous catheter-related infections (CRIs). MATERIALS AND
      METHODS: From December 2008 to June 2009, 428 peripherally inserted central
      catheters (PICCs) were placed by the interventional radiology service of a large
      metropolitan children's hospital. This retrospective study analyzed demographic
      and outcome data for the 125 patients in this group at high risk for venous CRI.
      Patients at high risk were those with active systemic infection, previous
      complicated central venous access, intensive care unit (ICU) admission,
      intestinal failure, transplantation, complex congenital heart disease, or renal
      failure. Patients (age, 7.6 y +/- 7.0; 73 male and 52 female) received a
      conventional or antibiotic-impregnated PICC, with 17 receiving more than one
      catheter. RESULTS: Of the 146 of 428 qualifying patient encounters (34%), 53
      patients received an antibiotic-impregnated PICC and 93 received a conventional
      PICC, representing 5,080 total catheter-days (CDs). The rates of CRIs per 1,000
      CDs, including catheter exit site infections and catheter-related bloodstream
      infections, were 0.86 for antibiotic-impregnated PICCs and 5.5 for conventional
      PICCs (P = .036). A propensity-based model predicts 15-fold greater infection
      free survival over the lifetime of the catheter in patients who receive an
      antibiotic-impregnated PICC (P < .001). Antibiotic-impregnated PICC recipients
      with active infection or ICU admission at the time of insertion had no catheter
      associated infections, compared with 3.42 and 9.46 infections per 1,000 CDs,
      respectively, for patients who received conventional PICCs. Patients with
      intestinal failure had 1.49 and 10 infections per 1,000 CDs with antibiotic
      impregnated versus conventional PICCs, respectively. CONCLUSIONS: Antibiotic
      impregnated long-term PICCs significantly improve infection-free catheter
      survival in pediatric patients at high risk.

PMID- 24581465
TI  - Clinical predictors of port infections within the first 30 days of placement.
AB  - PURPOSE: To identify risk factors for port infections within 30 days of
      placement. MATERIAL AND METHODS: A retrospective chart review of port placements
      from 2002-2009 was conducted. Patients who had port removals secondary to
      infection within the first 30 days of placement were included. This group of
      patients was compared with a control group of patients with ports with no
      evidence of infection. For every one patient with a port infection, two control
      subjects were chosen of the same gender and new port placement during the same
      month as the corresponding patient with an infected port. RESULTS: From 2002
      2009, 4,404 ports were placed. Of the 4,404 patients, 33 (0.7%) were found to
      have a port infection within 30 days of placement. Compared with the control
      group, the early infection group had a higher prevalence of leukopenia (21.2% vs
      6.1%, P = .039) and thrombocytopenia (33% vs 12%, P = .0158). There was also a
      higher prevalence of an inpatient hospital stay during port placement and high
      international normalized ratio in the early infection group. CONCLUSIONS: Low
      preoperative white blood cell and platelet counts were risk factors for early
      infection. Abnormal coagulation profiles and inpatient access of ports after
      placement could be additional risk factors.

PMID- 24581466
TI  - Vacuum-assisted thrombectomy device (AngioVac) in the management of symptomatic
      iliocaval thrombosis.
AB  - Three patients with complete iliocaval thrombosis causing symptomatic leg
      swelling failed initial treatment with standard pharmacomechanical techniques.
      The occluded segments of the inferior vena cava and iliac veins were subsequently
      treated with the AngioVac Cannula (AngioDynamics, Latham, New York) and
      extracorporeal venous bypass circuit. In each patient, symptoms improved after
      treatment. This report discusses potential benefits and ancillary techniques of
      using the AngioVac device for iliocaval venous thrombosis. 

PMID- 24581468
TI  - Uterine artery embolization using a transradial approach: initial experience and
      technique.
AB  - This study investigates the feasibility of performing uterine artery embolization
      (UAE) via transradial access (TRA). Growing evidence demonstrates significant
      benefits of TRA versus standard transfemoral access during percutaneous coronary
      intervention, now making it the preferred approach at many centers worldwide. At
      a single institution from March 2013 to October 2013, 29 consecutive patients
      were treated by transradial UAE. Technical success rate was 100%, with no
      immediate major or minor complications. The radial artery was patent at 1-month
      follow-up evaluation in all cases. These preliminary data suggest that
      transradial UAE is feasible and safe. 

PMID- 24581469
TI  - Percutaneous microwave ablation of renal tumors using a gas-cooled 2.4-GHz probe:
      technique and initial results.
AB  - The feasibility, safety, and preliminary effectiveness of microwave ablation
      (MWA) in the treatment of renal tumors using a high-powered, carbon dioxide
      cooled probe were evaluated. There were 15 tumors treated in 14 patients.
      Computed tomography was performed immediately after MWA, and follow-up imaging
      was performed to evaluate for recurrence. Immediate technical effectiveness was
      100%. One complication involved the formation of a renal artery pseudoaneurysm.
      At follow-up (mean interval, 12.5 wk) evaluation, 14 of 15 (93.3%) tumors
      demonstrated complete necrosis. MWA is a safe, effective treatment modality;
      larger studies are warranted to demonstrate long-term oncologic outcomes. 

PMID- 24581470
TI  - CO2 to live and to die.

PMID- 24581471
TI  - Intravascular US-guided transjugular intrahepatic portosystemic shunt creation in
      a second-trimester pregnancy to prophylactically decompress abdominal wall
      varices before cesarean section.

PMID- 24581472
TI  - Supraumbilical rash caused by nontarget radioembolization to the falciform
      artery.

PMID- 24581474
TI  - Celect filter penetration of aorta and lumbar artery.

PMID- 24581473
TI  - Sudden death from carcinoid crisis during image-guided biopsy of a lung mass.

PMID- 24581475
TI  - Transarterial embolization of large retroperitoneal ganglioneuromas.

PMID- 24581476
TI  - Response to "Hospital-admitting privileges in IR".

PMID- 24581477
TI  - Hospital-admitting privileges in IR.

PMID- 24581478
TI  - Commentary on "Still so far to go".

PMID- 24581479
TI  - Non-viability of crossing the Alzheimer mouse model Tg2576 with the type 2
      diabetes mouse model ob/ob.

PMID- 24581480
TI  - Age-associated changes of cerebrospinal fluid amyloid-beta and tau in cynomolgus
      monkeys.
AB  - Nonhuman primates (NHPs) are useful for the study of age-associated changes in
      the brain as a model that is biologically closely related to humans. For example,
      with age, all NHPs analyzed to date, develop beta-amyloid (Abeta) plaques as seen
      in humans. Nevertheless, it is still unclear if NHPs have human-like age
      associated changes in Abeta and tau protein in cerebrospinal fluid. The present
      study was an attempt to specifically address these issues. Cerebrospinal fluid
      levels of Abeta and phosphorylated tau were measured in 37 and 22 cynomolgus
      monkeys, respectively, with ages ranging from 4 to 22-year-old. The result from
      the present study revealed significant age-associated declines in Abeta42 levels
      but not in Abeta40 and phosphorylated tau levels. This finding appears to
      parallel changes seen with human aging, in which decreased levels of Abeta42 can
      be seen in normal older adults, and supporting that cynomolgus monkeys would be a
      useful model for studying age-related neurologic disorders associated with
      Alzheimer-like cerebral proteopathy. 

PMID- 24581481
TI  - Carbon ion radiotherapy for oligo-recurrent lung metastases from colorectal
      cancer: a feasibility study.
AB  - BACKGROUND: The purpose of this study was to evaluate the efficacy and
      feasibility of carbon ion radiotherapy (CIRT) for oligo-recurrent lung tumors
      from colorectal cancer (CRC). METHODS: From May 1997 to October 2012, 34
      consecutive patients with oligo-recurrent pulmonary metastases from CRC were
      treated with CIRT. The patients were not surgical candidates for medical reasons
      or patient refusal. Using a respiratory-gated technique, carbon ion therapy was
      delivered with curative intent using 4 coplanar beam angles. A median dose of 60
      GyE (range, 44-64.8 GyE) was delivered to the planning target volume (PTV), with
      a median daily dose of 15 GyE (range, 3.6-44 GyE). Treatment outcome was analyzed
      in terms of local control rate (LCR), survival rate, and treatment-related
      complications. RESULTS: In total, 34 patients with 44 oligo-recurrent pulmonary
      lesions were treated with CIRT. Median follow-up period was 23.7 months. The 2-
      and 3-year actuarial LCRs of the treated patients were 85.4% +/- 6.2% and 85.4%
      +/- 6.2%, respectively. Overall survival was 65.1% +/- 9.5% at 2 years, and 50.1%
      +/- 10.5% at 3 years. Although survival rates were relatively worse in the
      subsets of patients aged<63 years or with early metastasis (< 36 months after
      resection of primary site), these factors were not significantly correlated with
      overall survival (P=0.13 and 0.19, respectively). All treatment-related
      complications were self-limited, without any grade 3-5 toxicity. CONCLUSIONS:
      CIRT is one of the most effective nonsurgical treatments for colorectal lung
      metastases, which are relatively resistant to stereotactic body radiotherapy.
      CIRT is considered to be the least invasive approach even in patients who have
      undergone repeated prior thoracic metastasectomies.

PMID- 24581482
TI  - Paclitaxel coating on the terminal portion of hemodialysis grafts effectively
      suppresses neointimal hyperplasia in a porcine model.
AB  - OBJECTIVE: The local delivery of paclitaxel onto a graft has been reported to
      prevent neointimal hyperplasia. Because more than half of vascular stenoses occur
      within 3 cm of the venous anastomosis, this study tested the effectiveness of a
      paclitaxel coating restricted to both ends of the expanded
      polytetrafluoroethylene (ePTFE) graft to reduce the amount of drug delivered.
      METHODS: Both ends of ePTFE grafts were coated with paclitaxel at a dose of 0.58
      MUg/mm(2); the total amount of paclitaxel per graft was 0.66 mg. Paclitaxel
      coated hemodialysis grafts 15 cm in length were surgically implanted between the
      common carotid artery and external jugular vein in female Landrace pigs. The
      animals were sacrificed 6 weeks after graft placement. Cross sections of the
      anastomosis sites were analyzed histomorphometrically to measure the ratio of
      neointimal hyperplasia to the graft area (H/G ratio) and the percentage of
      luminal stenosis. The experimental results were compared between grafts coated
      with paclitaxel at the ends only (n = 8), grafts coated over the entire length (n
      = 6), and uncoated control grafts (n = 6). RESULTS: The mean +/- standard error
      values of the H/G ratios for the arterial anastomosis were 0.82 +/- 0.13
      (control), 0.41 +/- 0.09 (terminal coating), and 0.21 +/- 0.04 (whole coating).
      The values for the venous anastomosis were 0.82 +/- 0.12 (control), 0.39 +/- 0.11
      (terminal coating), and 0.12 +/- 0.03 (whole coating). Compared with the uncoated
      grafts, neointimal hyperplasia was suppressed effectively in the vascular grafts
      coated terminally with paclitaxel (artery, P = 050; vein, P < .001). However, the
      suppressive effect was less than that of grafts coated with paclitaxel over the
      entire length. The percentages of luminal stenosis showed similar tendency to the
      H/G ratios. CONCLUSIONS: Despite a reduced amount of the drug, paclitaxel coating
      applied to both ends of the ePTFE hemodialysis grafts effectively suppressed
      neointimal hyperplasia at the sites of anastomosis.

PMID- 24581483
TI  - Impact of velaglucerase alfa on bone marrow burden score in adult patients with
      type 1 Gaucher disease: 7-year follow-up.
AB  - BACKGROUND: Bone marrow infiltration by substrate-engorged "Gaucher" cells
      manifests early in Gaucher disease (GD). The impact of velaglucerase alfa on bone
      marrow burden (BMB) was evaluated as an exploratory assessment. METHODS: BMB
      scores were assessed using T1- and T2-weighted magnetic resonance images of the
      lumbar spine (LS) and femora among symptomatic GD patients who participated in
      the 9-month Phase I/II trial and long-term extension study for velaglucerase
      alfa. A post-hoc assessment of marrow involvement was performed. BMB scores per
      site are 0-8 (0/1=normal; 8=severe infiltration). RESULTS: The median LS-BMB
      score at baseline was 6 (n=12; range 3-8); at 9 months, compared with baseline,
      there was a median change of -2 (n=11; two-sided p-value=0.0078). LS-BMB scores
      continued to decrease through 5 years (n=8; median change from baseline -5
      [p=0.0078], median score 1 [range 1-4]) and were subsequently sustained through 7
      years (n=8). LS-BMB decreases of >=2 points occurred in 6/11 patients at 9
      months, and in all assessable patients (8/8) by 5 years. Long-term femoral BMB (F
      BMB) assessment was possible for three patients; all experienced reductions of
      >=2 points at 5 years with a total score (LS-BMB+F-BMB) decrease >=4.
      CONCLUSIONS: This post hoc analysis suggests improvement in BMB scores through 5
      years that was sustained through 7 years, despite dose reduction from 15 months.
      Prospective studies in a large cohort are needed to validate these findings.

PMID- 24581484
TI  - Interphase chromatin LINEd with RNA.
AB  - RNA has been proposed to be a component of an underlying nuclear matrix. Hall et
      al. show that noncoding, repetitive RNAs, some derived from LINE1 elements,
      stably associate with interphase chromosomes and copurify with nuclear scaffold,
      indicating that RNAs might impact interphase chromosome architecture. 

PMID- 24581485
TI  - Ribosome rescue, nearing the end.
AB  - In eukaryotes, Dom34 is involved in the rescue of ribosomes that stall on mRNAs
      during protein synthesis. Using ribosome profiling, Guydosh and Green reveal
      that, in addition to rescue of ribosomes stalled on truncated mRNAs, Dom34 also
      recycles ribosomes that are unexpectedly found in the 3' untranslated regions of
      many cellular mRNAs. 

PMID- 24581486
TI  - Nuclear pores set the speed limit for mitosis.
AB  - The spindle assembly checkpoint prevents separation of sister chromatids until
      each kinetochore is attached to the mitotic spindle. Rodriguez-Bravo et al.
      report that the nuclear pore complex scaffolds spindle assembly checkpoint
      signaling in interphase, providing a store of inhibitory signals that limits the
      speed of the subsequent mitosis. 

PMID- 24581487
TI  - Off the beaten track: new neurons in the adult human striatum.
AB  - In the adult brain, new neurons are produced in two "canonical" regions: the
      hippocampus and the olfactory bulb. Ernst et al. now show that, unlike other
      species, humans also display robust neurogenesis in the striatum, an unexpected
      finding with important physiological, pathological, and evolutionary
      implications. 

PMID- 24581488
TI  - A genotype-first approach to defining the subtypes of a complex disease.
AB  - Medical genetics typically entails the detailed characterization of a patient's
      phenotypes followed by genotyping to discover the responsible gene or mutation.
      Here, we propose that the systematic discovery of genetic variants associated
      with complex diseases such as autism are progressing to a point where a reverse
      strategy may be fruitful in assigning the pathogenic effects of many different
      genes and in determining whether particular genotypes manifest as clinically
      recognizable phenotypes. This "genotype-first" approach for complex disease
      necessitates the development of large, highly integrated networks of researchers,
      clinicians, and patient families, with the promise of improved therapies for
      subsets of patients. 

PMID- 24581489
TI  - Stop the biting: targeting a mosquito's sense of smell.
AB  - Mosquitoes are a great threat to human health. Fortunately, they have a weakness:
      they utilize their sense of smell to target a human host. Recent studies examine
      the effectiveness of protecting humans from attack by ablating or odorant
      targeting mosquito olfactory receptors. The results are both promising and
      alarming. 

PMID- 24581490
TI  - BAR domain scaffolds in dynamin-mediated membrane fission.
AB  - Biological membranes undergo constant remodeling by membrane fission and fusion
      to change their shape and to exchange material between subcellular compartments.
      During clathrin-mediated endocytosis, the dynamic assembly and disassembly of
      protein scaffolds comprising members of the bin-amphiphysin-rvs (BAR) domain
      protein superfamily constrain the membrane into distinct shapes as the pathway
      progresses toward fission by the GTPase dynamin. In this Review, we discuss how
      BAR domain protein assembly and disassembly are controlled in space and time and
      which structural and biochemical features allow the tight regulation of their
      shape and function to enable dynamin-mediated membrane fission. 

PMID- 24581491
TI  - Hippo signaling regulates microprocessor and links cell-density-dependent miRNA
      biogenesis to cancer.
AB  - Global downregulation of microRNAs (miRNAs) is commonly observed in human cancers
      and can have a causative role in tumorigenesis. The mechanisms responsible for
      this phenomenon remain poorly understood. Here, we show that YAP, the downstream
      target of the tumor-suppressive Hippo-signaling pathway regulates miRNA
      biogenesis in a cell-density-dependent manner. At low cell density, nuclear YAP
      binds and sequesters p72 (DDX17), a regulatory component of the miRNA-processing
      machinery. At high cell density, Hippo-mediated cytoplasmic retention of YAP
      facilitates p72 association with Microprocessor and binding to a specific
      sequence motif in pri-miRNAs. Inactivation of the Hippo pathway or expression of
      constitutively active YAP causes widespread miRNA suppression in cells and tumors
      and a corresponding posttranscriptional induction of MYC expression. Thus, the
      Hippo pathway links contact-inhibition regulation to miRNA biogenesis and may be
      responsible for the widespread miRNA repression observed in cancer.

PMID- 24581492
TI  - Stable C0T-1 repeat RNA is abundant and is associated with euchromatic interphase
      chromosomes.
AB  - Recent studies recognize a vast diversity of noncoding RNAs with largely unknown
      functions, but few have examined interspersed repeat sequences, which constitute
      almost half our genome. RNA hybridization in situ using C0T-1 (highly repeated)
      DNA probes detects surprisingly abundant euchromatin-associated RNA comprised
      predominantly of repeat sequences (C0T-1 RNA), including LINE-1. C0T-1
      hybridizing RNA strictly localizes to the interphase chromosome territory in cis
      and remains stably associated with the chromosome territory following prolonged
      transcriptional inhibition. The C0T-1 RNA territory resists mechanical disruption
      and fractionates with the nonchromatin scaffold but can be experimentally
      released. Loss of repeat-rich, stable nuclear RNAs from euchromatin corresponds
      to aberrant chromatin distribution and condensation. C0T-1 RNA has several
      properties similar to XIST chromosomal RNA but is excluded from chromatin
      condensed by XIST. These findings impact two "black boxes" of genome science: the
      poorly understood diversity of noncoding RNA and the unexplained abundance of
      repetitive elements. 

PMID- 24581493
TI  - Argonaute-bound small RNAs from promoter-proximal RNA polymerase II.
AB  - Argonaute (Ago) proteins mediate posttranscriptional gene repression by binding
      guide miRNAs to regulate targeted RNAs. To confidently assess Ago-bound small
      RNAs, we adapted a mouse embryonic stem cell system to express a single epitope
      tagged Ago protein family member in an inducible manner. Here, we report the
      small RNA profile of Ago-deficient cells and show that Ago-dependent stability is
      a common feature of mammalian miRNAs. Using this criteria and immunopurification,
      we identified an Ago-dependent class of noncanonical miRNAs derived from protein
      coding gene promoters, which we name transcriptional start site miRNAs (TSS
      miRNAs). A subset of promoter-proximal RNA polymerase II (RNAPII) complexes
      produces hairpin RNAs that are processed in a DiGeorge syndrome critical region
      gene 8 (Dgcr8)/Drosha-independent but Dicer-dependent manner. TSS-miRNA activity
      is detectable from endogenous levels and following overexpression of mRNA
      constructs. Finally, we present evidence of differential expression and
      conservation in humans, suggesting important roles in gene regulation. 

PMID- 24581494
TI  - Dom34 rescues ribosomes in 3' untranslated regions.
AB  - Ribosomes that stall before completing peptide synthesis must be recycled and
      returned to the cytoplasmic pool. The protein Dom34 and cofactors Hbs1 and Rli1
      can dissociate stalled ribosomes in vitro, but the identity of targets in the
      cell is unknown. Here, we extend ribosome profiling methodology to reveal a high
      resolution molecular characterization of Dom34 function in vivo. Dom34 removes
      stalled ribosomes from truncated mRNAs, but, in contrast, does not generally
      dissociate ribosomes on coding sequences known to trigger stalling, such as
      polyproline. We also show that Dom34 targets arrested ribosomes near the ends of
      3' UTRs. These ribosomes appear to gain access to the 3' UTR via a mechanism that
      does not require decoding of the mRNA. These results suggest that ribosomes
      frequently enter downstream noncoding regions and that Dom34 carries out the
      important task of rescuing them. 

PMID- 24581495
TI  - Hsp90-Tau complex reveals molecular basis for specificity in chaperone action.
AB  - Protein folding in the cell relies on the orchestrated action of conserved
      families of molecular chaperones, the Hsp70 and Hsp90 systems. Hsp70 acts early
      and Hsp90 late in the folding path, yet the molecular basis of this timing is
      enigmatic, mainly because the substrate specificity of Hsp90 is poorly
      understood. Here, we obtained a structural model of Hsp90 in complex with its
      natural disease-associated substrate, the intrinsically disordered Tau protein.
      Hsp90 binds to a broad region in Tau that includes the aggregation-prone repeats.
      Complementarily, a 106-A-long substrate-binding interface in Hsp90 enables many
      low-affinity contacts. This allows recognition of scattered hydrophobic residues
      in late folding intermediates that remain after early burial of the Hsp70 sites.
      Our model resolves the paradox of how Hsp90 specifically selects for late folding
      intermediates but also for some intrinsically disordered proteins-through the
      eyes of Hsp90 they look the same. 

PMID- 24581496
TI  - Interplay of acetyltransferase EP300 and the proteasome system in regulating heat
      shock transcription factor 1.
AB  - When exposed to proteotoxic environmental conditions, mammalian cells activate
      the cytosolic stress response in order to restore protein homeostasis. A key
      feature of this response is the heat shock transcription factor 1 (HSF1)
      dependent expression of molecular chaperones. Here, we describe the results of an
      RNA interference screen in HeLa cells to identify modulators of stress response
      induction and attenuation. The modulator proteins are localized in multiple
      cellular compartments, with chromatin modifiers and nuclear protein quality
      control playing a central regulatory role. We find that the acetyltransferase,
      EP300, controls the cellular level of activatable HSF1. This involves acetylation
      of HSF1 at multiple lysines not required for function and results in
      stabilization of HSF1 against proteasomal turnover. Acetylation of functionally
      critical lysines during stress serves to fine-tune HSF1 activation. Finally, the
      nuclear proteasome system functions in attenuating the stress response by
      degrading activated HSF1 in a manner linked with the clearance of misfolded
      proteins. 

PMID- 24581497
TI  - Broad-spectrum therapeutic suppression of metastatic melanoma through nuclear
      hormone receptor activation.
AB  - Melanoma metastasis is a devastating outcome lacking an effective preventative
      therapeutic. We provide pharmacologic, molecular, and genetic evidence
      establishing the liver-X nuclear hormone receptor (LXR) as a therapeutic target
      in melanoma. Oral administration of multiple LXR agonists suppressed melanoma
      invasion, angiogenesis, tumor progression, and metastasis. Molecular and genetic
      experiments revealed these effects to be mediated by LXRbeta, which elicits these
      outcomes through transcriptional induction of tumoral and stromal apolipoprotein
      E (ApoE). LXRbeta agonism robustly suppressed tumor growth and metastasis across
      a diverse mutational spectrum of melanoma lines. LXRbeta targeting significantly
      prolonged animal survival, suppressed the progression of established metastases,
      and inhibited brain metastatic colonization. Importantly, LXRbeta activation
      displayed melanoma-suppressive cooperativity with the frontline regimens
      dacarbazine, B-Raf inhibition, and the anti-CTLA-4 antibody and robustly
      inhibited melanomas that had acquired resistance to B-Raf inhibition or
      dacarbazine. We present a promising therapeutic approach that uniquely acts by
      transcriptionally activating a metastasis suppressor gene. 

PMID- 24581498
TI  - Serpins promote cancer cell survival and vascular co-option in brain metastasis.
AB  - Brain metastasis is an ominous complication of cancer, yet most cancer cells that
      infiltrate the brain die of unknown causes. Here, we identify plasmin from the
      reactive brain stroma as a defense against metastatic invasion, and plasminogen
      activator (PA) inhibitory serpins in cancer cells as a shield against this
      defense. Plasmin suppresses brain metastasis in two ways: by converting membrane
      bound astrocytic FasL into a paracrine death signal for cancer cells, and by
      inactivating the axon pathfinding molecule L1CAM, which metastatic cells express
      for spreading along brain capillaries and for metastatic outgrowth. Brain
      metastatic cells from lung cancer and breast cancer express high levels of anti
      PA serpins, including neuroserpin and serpin B2, to prevent plasmin generation
      and its metastasis-suppressive effects. By protecting cancer cells from death
      signals and fostering vascular co-option, anti-PA serpins provide a unifying
      mechanism for the initiation of brain metastasis in lung and breast cancers. 

PMID- 24581499
TI  - Nuclear pores protect genome integrity by assembling a premitotic and Mad1
      dependent anaphase inhibitor.
AB  - The spindle assembly checkpoint (SAC) delays anaphase until all chromosomes are
      bioriented on the mitotic spindle. Under current models, unattached kinetochores
      transduce the SAC by catalyzing the intramitotic production of a diffusible
      inhibitor of APC/C(Cdc20) (the anaphase-promoting complex/cyclosome and its
      coactivator Cdc20, a large ubiquitin ligase). Here we show that nuclear pore
      complexes (NPCs) in interphase cells also function as scaffolds for anaphase
      inhibitory signaling. This role is mediated by Mad1-Mad2 complexes tethered to
      the nuclear basket, which activate soluble Mad2 as a binding partner and
      inhibitor of Cdc20 in the cytoplasm. Displacing Mad1-Mad2 from nuclear pores
      accelerated anaphase onset, prevented effective correction of merotelic errors,
      and increased the threshold of kinetochore-dependent signaling needed to halt
      mitosis in response to spindle poisons. A heterologous Mad1-NPC tether restored
      Cdc20 inhibitor production and normal M phase control. We conclude that nuclear
      pores and kinetochores both emit "wait anaphase" signals that preserve genome
      integrity. 

PMID- 24581500
TI  - NLRP6 inflammasome orchestrates the colonic host-microbial interface by
      regulating goblet cell mucus secretion.
AB  - Mucus production by goblet cells of the large intestine serves as a crucial
      antimicrobial protective mechanism at the interface between the eukaryotic and
      prokaryotic cells of the mammalian intestinal ecosystem. However, the regulatory
      pathways involved in goblet cell-induced mucus secretion remain largely unknown.
      Here, we demonstrate that the NLRP6 inflammasome, a recently described regulator
      of colonic microbiota composition and biogeographical distribution, is a critical
      orchestrator of goblet cell mucin granule exocytosis. NLRP6 deficiency leads to
      defective autophagy in goblet cells and abrogated mucus secretion into the large
      intestinal lumen. Consequently, NLRP6 inflammasome-deficient mice are unable to
      clear enteric pathogens from the mucosal surface, rendering them highly
      susceptible to persistent infection. This study identifies an innate immune
      regulatory pathway governing goblet cell mucus secretion, linking
      nonhematopoietic inflammasome signaling to autophagy and highlighting the goblet
      cell as a critical innate immune player in the control of intestinal host
      microbial mutualism. PAPERCLIP: 

PMID- 24581501
TI  - Multimodal integration of carbon dioxide and other sensory cues drives mosquito
      attraction to humans.
AB  - Multiple sensory cues emanating from humans are thought to guide blood-feeding
      female mosquitoes to a host. To determine the relative contribution of carbon
      dioxide (CO2) detection to mosquito host-seeking behavior, we mutated the AaegGr3
      gene, a subunit of the heteromeric CO2 receptor in Aedes aegypti mosquitoes. Gr3
      mutants lack electrophysiological and behavioral responses to CO2. These mutants
      also fail to show CO2-evoked responses to heat and lactic acid, a human-derived
      attractant, suggesting that CO2 can gate responses to other sensory stimuli.
      Whereas attraction of Gr3 mutants to live humans in a large semi-field
      environment was only slightly impaired, responses to an animal host were greatly
      reduced in a spatial-scale-dependent manner. Synergistic integration of heat and
      odor cues likely drive host-seeking behavior in the absence of CO2 detection. We
      reveal a networked series of interactions by which multimodal integration of CO2,
      human odor, and heat orchestrates mosquito attraction to humans. 

PMID- 24581502
TI  - Reciprocal encoding of signal intensity and duration in a glucose-sensing
      circuit.
AB  - Cells continuously adjust their behavior in response to changing environmental
      conditions. Both intensity and duration of external signals are critical factors
      in determining what response is initiated. To understand how intracellular
      signaling networks process such multidimensional information, we studied the
      AtRGS1-mediated glucose response system of Arabidopsis. By combining experiments
      with mathematical modeling, we discovered a reciprocal dose and duration response
      relying on the orchestrated action of three kinases (AtWNK1, AtWNK8, and AtWNK10)
      acting on distinct timescales and activation thresholds. Specifically, we find
      that high concentrations of D-glucose rapidly signal through AtWNK8 and AtWNK10,
      whereas low, sustained sugar concentration slowly activate the pathway through
      AtWNK1, allowing the cells to respond similarly to transient, high-intensity
      signals and sustained, low-intensity signals. This "dose-duration reciprocity"
      allows encoding of both the intensity and persistence of glucose as an important
      energy resource and signaling molecule. 

PMID- 24581504
TI  - SnapShot: adult hippocampal neurogenesis.

PMID- 24581503
TI  - Neural networks of the mouse neocortex.
AB  - Numerous studies have examined the neuronal inputs and outputs of many areas
      within the mammalian cerebral cortex, but how these areas are organized into
      neural networks that communicate across the entire cortex is unclear. Over 600
      labeled neuronal pathways acquired from tracer injections placed across the
      entire mouse neocortex enabled us to generate a cortical connectivity atlas. A
      total of 240 intracortical connections were manually reconstructed within a
      common neuroanatomic framework, forming a cortico-cortical connectivity map that
      facilitates comparison of connections from different cortical targets.
      Connectivity matrices were generated to provide an overview of all intracortical
      connections and subnetwork clusterings. The connectivity matrices and cortical
      map revealed that the entire cortex is organized into four somatic sensorimotor,
      two medial, and two lateral subnetworks that display unique topologies and can
      interact through select cortical areas. Together, these data provide a resource
      that can be used to further investigate cortical networks and their corresponding
      functions. 

PMID- 24581505
TI  - Repetitive extracorporeal shock wave applications are superior in inducing
      angiogenesis after full thickness burn compared to single application.
AB  - OBJECTIVE: Burn wounds remain a challenge due to subsequent wound infection and
      septicemia, which can be prevented by acceleration of wound healing. The aim of
      the study was to analyze microcirculation and leukocyte endothelium interaction
      with particular focus on angiogenesis after full-thickness burn using three
      different repetitions of low energy shock waves. METHODS: Full-thickness burns
      were inflicted to the ears of hairless mice (n=44; area: 1.6+/-0.05 mm2 (mean+/
      SEM)). Mice were randomized into four groups: the control group received a burn
      injury but no shock waves; group A received ESWA (0.03 mJ/mm2) on day one after
      burn injury; group B received shock waves on day one and day three after burn
      injury; group C ESWA on day one, three and seven after burn injury. Intravital
      fluorescent microscopy was used to assess microcirculatory parameters,
      angiogenesis and leukocyte interaction. Values were obtained before burn
      (baseline value) immediately after and on days 1, 3, 7 and 12 after burn.
      RESULTS: Shock-wave treated groups showed significantly accelerated angiogenesis
      compared to the control group. The non-perfused area (NPA) is regarded as a
      parameter for angiogenesis and showed the following data on day 12 2.7+/-0.4%
      (group A, p=0.001), 1.4+/-0.5% (group B, p<0.001), 1.0+/-0.3% (group C, p<0.001),
      6.1+/-0.9% (control group). Edema formation is positively correlated with the
      number of shock wave applications: day 12: group A: 173.2+/-9.8%, group B:
      184.2+/-6.6%, group C: 201.1+/-6.9%, p=0.009 vs. control: 162.3+/-8.7% (all data:
      mean+/-SEM). CONCLUSION: According to our data shock waves positively impact the
      wound healing process following burn injury. Angiogenesis showed significantly
      improved activity after shock wave application. In all three treatment groups
      angiogenesis was higher compared to the control group. Within the ESWA groups,
      double applications showed better results than single application and three
      applications showed better results than single or double applications.

PMID- 24581508
TI  - A novel NCSTN mutation alone may be insufficient for the development of familial
      hidradenitis suppurativa.

PMID- 24581509
TI  - Defective maintenance of pH of stratum corneum is correlated with preferential
      emergence and exacerbation of atopic-dermatitis-like dermatitis in flaky-tail
      mice.
AB  - BACKGROUND: Neutralization of stratum corneum (SC) pH, which is induced by a
      variety of stimuli, such as scratching, use of soap and inflammation, can
      stimulate activity of serine protease (SPase). Activation of SPase induces
      production of thymic stromal lymphopoietin (TSLP) through protease-activated
      receptor-2. Both reduced expression of natural moisturizing factors, which are
      required for maintenance of SC pH, and the preferential development of atopic
      dermatitis (AD)-like dermatitis are found in flaky-tail mice (FTM) with a loss-of
      function mutation in filaggrin. OBJECTIVE: We examined possible correlations
      between disturbance of responses to an exogenous stimulus of SC neutralization
      and the preferential emergence of AD-like dermatitis in FTM. METHODS: FTM and
      wild-type mice (C57BL/6) were subjected to an SC-neutralization stimulus via
      application of 1,1,3,3-tetramethylguanidine (TMG). TMG was applied to young mice
      at a time when FTM had not yet developed significant dermatitis, and we examined
      their ability to maintain SC acidity and several parameters associated with AD
      like dermatitis. RESULTS: The recovery of SC pH after the application of TMG was
      delayed in FTM, presumably because of unchanged expression of Na(+)/H(+)
      antiporter 1, which is involved in maintenance of SC acidity. Cutaneous
      inflammation with elevated SPase activity and serum levels of TSLP, thymus and
      activation-regulated chemokine and IgE were induced only in TMG-treated FTM.
      CONCLUSION: Our results suggest that defective maintenance of pH of SC is
      correlated with emergence and exacerbation of AD-like dermatitis in FTM.

PMID- 24581510
TI  - Genomic profiling of type-1 adult diabetic and aged normoglycemic mouse liver.
AB  - BACKGROUND: Hyperglycemia induces chromatin remodeling with consequences on
      differential gene expression in mouse hepatocytes, similar to what occurs during
      aging. The liver is the central organ for the regulation of glucose homeostasis
      and xenobiotic and lipid metabolism and is affected by insulin signaling. The
      precise transcriptional profiling of the type-1 diabetic liver and its comparison
      to aging have not been elucidated yet. METHODS: Here, we studied the differential
      genomic expression of mouse liver cells under adult hyperglycemic and aged
      normoglycemic conditions using expression arrays. RESULTS: Differential gene
      expression involved in an increase in glucose and impaired lipid metabolism were
      detected in the type-1 diabetic liver. In this regard, Ppargc1a presents an
      increased expression and is a key gene that might be regulating both processes.
      The differential gene expression observed may also be associated with hepatic
      steatosis in diabetic mouse liver, as a secondary disease. Similarly, middle-aged
      mice presented differential expression of genes involved in glucose, lipid and
      xenobiotic metabolism. These genes could be associated with an increase in
      polyploidy, but the consequences of differential expression were not as drastic
      as those observed in diabetic animals. CONCLUSIONS: Taken together, these
      findings provide new insights into gene expression profile changes in type-1
      diabetic liver. Ppargc1a was found to be the key-gene that increases glucose
      metabolism and impairs lipid metabolism impairment. The novel results reported
      here open new areas of investigation in diabetic research and facilitate the
      development of new strategies for gene therapy.

PMID- 24581511
TI  - Bacterial persistence in the prostate after antibiotic treatment of chronic
      bacterial prostatitis in men with spinal cord injury.
AB  - OBJECTIVE: To investigate the microbiologic outcome after antibiotic treatment of
      bacterial prostatitis in men with spinal cord injury (SCI). METHODS: A
      retrospective investigation was done in an SCI rehabilitation center. The
      microbiologic culture results of urine and ejaculate or prostatic fluid samples
      were collected from 34 men with SCI presenting with recurrent urinary tract
      infections and bacterial prostatitis. Furthermore, patient characteristics,
      bladder diary details, and the administered antibiotic treatment were collected.
      RESULTS: The median age of the 34 investigated men was 42.5 years (lower
      quartile, 31.8; upper quartile, 46.1 years), and they had sustained SCI a median
      of 15.2 years (lower quartile, 4.7; upper quartile, 22.9 years) ago. The majority
      (24 of 34 patients; 71%) evacuated their bladder with intermittent
      catheterization. The most commonly used antibiotics to treat bacterial
      prostatitis were fluoroquinolones (n = 41) followed by trimethoprim
      sulfamethoxazole (n = 8) and second-generation cephalosporins (n = 7). In merely
      2 men, antibiotic treatment resulted in bacterial eradication from the prostate.
      A shift in the bacteria species identified in the ejaculate or prostatic fluid
      cultures was observed during the follow-up. Most men (28 of 34; 82%) presented
      with mostly the same bacteria (55 of 62, 89%) in the urine as in the ejaculate or
      prostate samples. CONCLUSION: Antibiotic treatment did not result in the
      eradication of bacteria from the prostate of men with SCI. The antibiotic
      treatment of bacterial prostatitis in men with SCI should aim at eradicating
      symptoms and not bacteria.

PMID- 24581513
TI  - Editorial comment.

PMID- 24581515
TI  - The phytotherapeutic agent, eviprostat, suppresses stromal proliferation and
      inflammation even after establishment of nonbacterial prostatitis in the rat
      prostate.
AB  - OBJECTIVE: To evaluate the effect of phytotherapeutic agent, Eviprostat,
      administered after the establishment of nonbacterial prostatitis (NBP) on the
      stroma-to-epithelium ratio (S/E ratio), inflammatory scores, tissue macrophage
      infiltration, and cytokines and chemokines levels in prostate tissue and urine.
      MATERIALS AND METHODS: Ten-month-old male Wistar rats were castrated and exposed
      to 17-beta-isomer of estradiol for 30 days to induce NBP. Twenty-five NBP rats
      were divided into 5 groups: (1) NBP (0) rats sacrificed immediately after the
      establishment of NBP; (2,3) NBP (30)/control (CTL) and NBP (30)/Eviprostat (EVI)
      rats fed without or with 0.1% Eviprostat under estradiol-free for 30 days,
      respectively; and (4,5) NBP (60)/CTL and NBP (60)/EVI rats fed without or with
      0.1% Eviprostat under estradiol-free for 60 days, respectively. The S/E ratio,
      inflammatory scores, and the number of macrophage infiltration in the prostate
      were assessed. Concentrations of cytokines and chemokines in prostatic tissue and
      urine were measured by enzyme-linked immunosorbent assay. RESULTS: The S/E ratio
      was significantly increased with time until 60 days under estradiol-free
      condition (P <.001). The S/E ratio and the inflammatory scores in NBP (60)/EVI
      was significantly lower than that of NBP (60)/CTL (P <.001, and P = .022,
      respectively). The mean tissue concentration of chemokine ligand 2
      (CCL2)/monocyte chemoattractant protein-1 (MCP-1) in NBP (60)/CTL was
      significantly higher than that in NBP (0) (P = .016), whereas, there was no
      difference between NBP (60)/EVI and NBP (0). Furthermore, urinary CCL2/MCP-1 was
      significantly decreased in NBP (60)/EVI as compared with NBP (0) (P = .028).
      CONCLUSION: Eviprostat suppresses the stromal proliferation and inflammation in
      the rat prostate after the establishment of NBP at least partly owing to
      inhibitory effect on CCL2/MCP-1 production in the prostate.

PMID- 24581512
TI  - Immunoglobulin G4-related prostatitis: a case-control study focusing on clinical
      and pathologic characteristics.
AB  - OBJECTIVE: To evaluate the occurrence and histopathologic characteristics of
      immunoglobulin G4 (IgG4)-related prostatic involvement in patients diagnosed with
      autoimmune pancreatitis. METHODS: Nine cases of IgG4-related prostatitis were
      identified among 117 men in the autoimmune pancreatitis and IgG4-associated
      cholangitis patient databases in 2 tertiary hospitals. Clinical information was
      retrieved, and available prostatic tissue samples and 18 prostatitis control
      samples were evaluated for characteristic IgG4-related disease (IgG4-RD)
      features: maximum number of IgG4-positive cells per high-power field; dense
      lymphoplasmacytic infiltrate; fibrosis, arranged at least focally in a storiform
      pattern; phlebitis with or without obliteration of the lumen; and increased
      number of eosinophils. RESULTS: The aspecific sign of urine retention was
      commonly present in IgG4-RD patients with prostatic involvement. In these
      patients with IgG4-related prostatitis, the median number of IgG4-positive cells
      in prostatic tissue was 150 (interquartile range, 20-150) per high-power field
      compared with a median of 3 (interquartile range, 1-11) in control patients (P =
      .008). Dense lymphoplasmacytic infiltrate was observed in most (86% in cases and
      72% in control patients) tissue samples independent of the underlying cause of
      prostatitis. Fibrosis in at least a focally storiform pattern was seen rarely in
      both groups, and (obliterative) phlebitis was absent in all patients.
      Furthermore, eosinophil numbers were more often elevated in patients with IgG4-RD
      compared with controls (P <.001). In 2 cases, amelioration of the prostatitis
      symptoms on corticosteroid treatment was documented. CONCLUSION: Prostatic
      involvement might not be rare in patients with pancreatic or biliary IgG4-RD.
      Clinicians should consider this disease entity in patients with IgG4-RD and
      prostatic symptoms.

PMID- 24581516
TI  - Indenter study: associations between prostate elasticity and lower urinary tract
      symptoms.
AB  - OBJECTIVE: To investigate the associations between prostate elasticity and lower
      urinary tract symptoms (LUTS). METHODS: From August 2009 to December 2009, 48
      patients with no history of neoadjuvant therapy or previous prostate surgery who
      underwent robot-assisted radical prostatectomy were included in this study. A
      novel palpation system was used to measure the tissue elasticity of the prostate
      specimens. The elasticity of the prostate was defined as the mean elastic modulus
      (kilopascals [kPa]) of 21 sites from the posterior surface of prostate. All
      patients completed an International Prostate Symptoms Score questionnaire before
      surgery, and LUTS was defined as an International Prostate Symptoms Score total
      of >=8. Significant voiding symptoms were identified by a score of >=5 on the
      basis of patient responses to 4 questions (Q1, Q3, Q5, and Q6), and storage
      symptoms were identified by a score >=4 on the basis of patient responses to 3
      questions (Q2, Q4, and Q7). RESULTS: The median elastic modulus of the prostate
      was 20.8 kPa (interquartile range 15.6-22.9), and the LUTS incidences and voiding
      symptoms were significantly higher in patients with an elastic modulus >20 kPa.
      The multivariate logistic regression results indicated that a higher elastic
      modulus (as a continuous variable) was independently associated with voiding
      symptoms (odds ratio 1.18, P = .038) after controlling for age and prostate
      volume. However, the elastic modulus was not independently associated with LUTS
      or storage symptoms. CONCLUSION: Patients with greater prostate stiffness are
      more likely to develop LUTS. Specifically, prostate elasticity was independently
      associated with voiding symptoms.

PMID- 24581517
TI  - Editorial comment.

PMID- 24581519
TI  - Efficacy and safety of ultrasound-guided transrectal ethanol injection for the
      treatment of benign prostatic hyperplasia in patients with high-risk
      comorbidities: a long-term study at a single tertiary care institution.
AB  - OBJECTIVE: To evaluate the efficacy and safety of ultrasound-guided transrectal
      ethanol injection for the treatment of benign prostatic hyperplasia (BPH) in
      patients with high-risk comorbidities. METHODS: Seventy patients with BPH who
      showed poor oral drug efficacy and were medically fragile or unwilling to undergo
      operative therapy were enrolled in the study. They received ultrasound-guided
      transrectal ethanol injection and were followed up at 1, 3, 6, 12, and 24 months
      post-treatment. Volume and pathology of the prostate were observed. International
      prostate symptom score, quality of life, maximum urinary flow rate (Qmax), and
      postvoid residual volume were determined. The clinical complications were also
      recorded. RESULTS: After 24 months of treatment, prostate volume, international
      prostate symptom score, quality of life score, and postvoid residual of patients
      were significantly reduced when compared with the pretreatment values (55.9 +/-
      16.7 vs 46.8 +/- 8.1 mL, 29.3 +/- 6.7 vs 9.8 +/- 2.4 points, 5.3 +/- 1.7 vs 1.9
      +/- 0.7 points, and 130.8 +/- 71.5 vs 25.9 +/- 12.0 mL, respectively, P <.05).
      Qmax significantly increased to 15.3 +/- 3.2 mL/s than the pretreatment Qmax of
      4.7 +/- 3.1 mL/s (P = .001). Four of 36 patients who received a high dose of
      ethanol developed liquefaction necrosis and urinary tract injury (2 patients
      each). However, the subsequent 34 patients received a reduced dose of ethanol and
      had no complications. CONCLUSION: The minimally invasive technique of ultrasound
      guided transrectal ethanol injections showed good efficacy with few complications
      for the treatment of patients with BPH and other high-risk comorbidities.

PMID- 24581520
TI  - Editorial comment.

PMID- 24581521
TI  - A commentary on PSA velocity and doubling time for clinical decisions in prostate
      cancer.
AB  - Although the value of prostate-specific antigen (PSA) velocity or doubling time
      has never been seriously questioned for aiding the clinical management of
      recurrent or advanced cancer, there has historically been considerable
      uncertainty about PSA kinetics for decisions about biopsy and initial treatment.
      Recent studies, including analyses of cohorts from all the major randomized
      trials of localized prostate cancer, have failed to find any evidence that PSA
      velocity and application of PSA cutpoints are of benefit in this setting. Given
      current data on PSA velocity and doubling time, we propose the following "take
      home" messages for the practicing urologist: (1) High PSA velocity is not an
      indication for biopsy; (2) for men with a low total PSA but a high PSA velocity,
      consideration should be given to having PSA taken at a shorter interval; (3) men
      with an indication for biopsy should be biopsied irrespective of PSA velocity;
      (4) changes in PSA after negative biopsy findings do not determine the need for
      repeat biopsy; (5) monitoring PSA over time can aid judgment in decisions about
      biopsy, as informed by the clinical context; (6) PSA velocity is uninformative of
      risk at diagnosis; (7) high PSA velocity is not an indication for treatment in
      men on active surveillance; (8) PSA velocity at the time of recurrence should be
      entered into prediction models (or "nomograms") to aid patient counseling; (9)
      PSA changes after treatment for advanced disease can help indicate therapeutic
      response. 

PMID- 24581522
TI  - Editorial comment.

PMID- 24581524
TI  - Prostate cancer antigen 3: diagnostic outcomes in men presenting with urinary
      prostate cancer antigen 3 scores >=100.
AB  - OBJECTIVE: To describe the results of 3 rounds of diagnostic testing and linkage
      to the Dutch Cancer Registry for men with an initial prostate cancer antigen 3
      (PCA3) score >=100. METHODS: Within an earlier reported comparative study of PCA3
      vs prostate-specific antigen in a prescreened population, 90 men with a PCA3
      score >=100 were identified and underwent biopsy, 28 prostate cancers (PCs) were
      found, 62 men remained at risk of a diagnosis of PC. All men were offered repeat
      testing; 6 PCs were found in 20 men at rebiopsy. Men with at least 1 negative
      biopsy (n = 56) were invited to undergo magnetic resonance imaging (MRI) studies
      and MRI-guided biopsies if indicated. Linkage to the Dutch Cancer Registry after
      2.8 years of follow-up was performed for men with negative biopsies. RESULTS: Of
      the 56 men at risk, 28 agreed to participate in further testing. They were
      offered MRI studies; only 7 men agreed, and in 2, suspicious lesions were found
      and biopsies carried out. Only 1 PC was diagnosed and classified as T1c, Gleason
      3 + 3 = 6. The overall findings of 3 rounds of testing and of linkage to the
      cancer registry show that eventually 35 PCs were detected in 90 men with PCA3
      scores >=100 (positive predictive value 38.9%). CONCLUSION: Finding no PC despite
      extended diagnostic efforts in many men with initial PCA3 scores >=100 is
      unexpected and might be clinically relevant.

PMID- 24581525
TI  - Fragmentation of transrectal ultrasound-guided biopsy cores is influenced by the
      method of specimen retrieval.
AB  - OBJECTIVE: To determine whether the method of specimen preparation after
      transrectal ultrasound-guided biopsy of the prostate affected core fragmentation,
      and secondly to determine whether such fragmentation was influenced by the
      presence of malignancy in the biopsy specimen. METHODS: A prospective randomized
      study comparing 2 different mechanisms of specimen preparation, wash vs swipe of
      biopsy cores, with blinded assessment by a specific uropathologist was
      undertaken. RESULTS: For those cores in which prostate cancer was present, the
      wash method of specimen preparation resulted in fewer and longer core fragments
      (P = .005). Those patients in whom cancer was present on biopsy also had a
      greater degree of biopsy core fragmentation in those cores in which only benign
      tissue was identified (P = .017). Gleason score did not appear to influence the
      extent of fragmentation. CONCLUSION: The method of specimen preparation at
      prostate biopsy influences the degree of fragmentation seen at histologic
      evaluation. This has the potential to affect the interpretation of biopsy
      results, including suitability of patients for inclusion in active surveillance
      protocols. Core fragmentation might be minimized by modification of technique.

PMID- 24581526
TI  - CORPUS--novel COmplete Reconstruction of the Posterior Urethral Support after
      robotic radical prostatectomy: preliminary data of very early continence
      recovery.
AB  - INTRODUCTION: To determine whether a novel intraoperative technique of COmplete
      Reconstruction of the Posterior Urethral Support (CORPUS) improves early urinary
      continence after robotic-assisted radical prostatectomy (RARP). In this
      prospective study, between November 2012 and June 2013, 36 consecutive patients
      suitable for non-nerve-sparing RARP were alternatively assigned to either CORPUS
      surgery or Rocco's standard reconstruction. TECHNICAL CONSIDERATIONS: In the
      CORPUS group, fibers of the bilateral portions of the puborectalis muscle were
      used to create a sort of posterior hammock for the urethra. The International
      Consultation on Incontinence Questionnaire, Short Form Questionnaire (ICIQ-SF)
      and International Prostate Symptom Score were collected for all patients
      preoperatively and then ICIQ-SF at 1 day and both tests at 30 days after catheter
      removal after RARP. Intraoperative and/or postoperative complications were
      evaluated. Pearson chi-square test compared urinary continence according to ICIQ
      SF at 1 and 30 days. Statistical significance was set at P <.05. CONCLUSION:
      Fifty percent of CORPUS patients were continent immediately after catheter
      removal and 83% after 30 days. In controls, the respective percentages were 16%
      and 61%. The differences were statistically significant in both cases. The
      International Prostate Symptom Score at 30 days did not show obstructive symptoms
      in either group. One limitation of this study is the low number of cases,
      "superselected" to evaluate the true effect of CORPUS reconstruction. The very
      early continence rate of the CORPUS patients was significantly improved compared
      with that of patients undergoing Rocco's standard technique. Further studies
      extending the inclusion criteria are needed to confirm the impact of the new
      CORPUS technique in a more heterogeneous group.

PMID- 24581527
TI  - Population-based comparative effectiveness of salvage radical prostatectomy vs
      cryotherapy.
AB  - OBJECTIVE: To characterize population-based practice patterns, disease-specific
      and overall mortality, and cost associated with salvage cryotherapy (SCT) vs
      salvage radical prostatectomy (SRP). METHODS: We retrospectively identified 440
      men who failed primary radiation therapy and subsequently underwent SCT (n = 341,
      77.5%) or SRP (n = 99, 22.5%) between 1992 and 2009 from Surveillance,
      Epidemiology, and End Results-Medicare linked data. Propensity score analyses
      were used to compare overall and prostate cancer-specific mortality and
      associated Medicare expenditures for SRP vs SCT. RESULTS: Men undergoing SCT were
      more likely to be white (P <.001), less likely to be high school graduates (P =
      .008), and experienced shorter median time from diagnosis to salvage therapy
      (44.1 vs 60.1, P <.001) and from primary radiotherapy to salvage therapy (38.7 vs
      55.8 months, P <.001). In adjusted analyses, overall mortality was higher (21.6
      vs 6.1 deaths/100 person years, P <.001) for SRP vs SCT. There was a trend for
      higher prostate cancer-specific death rates with SRP vs SCT (6.5 vs 1.4
      deaths/100 person years, P = .061). Medicare expenditures for SRP vs SCT were
      more than 2-fold higher ($19,543 vs $8,088, P <.001). CONCLUSION: SRP vs SCT is
      associated with higher overall mortality and greater health care expenditures.
      However, longer follow-up is needed to assess long-term functional outcomes and
      cancer control.

PMID- 24581528
TI  - Quality of life and health status among prostate cancer survivors and noncancer
      population controls.
AB  - OBJECTIVE: To examine whether quality of life (QOL), health status, and the
      relationships between them varied by having a prostate cancer history. This study
      helps to inform the interface between aging-related health decline and the
      survival state among older men with prostate cancer, which is an important yet
      understudied public health issue. METHODS: Hierarchical linear models were used
      to analyze the cross-sectional data from the nationally representative population
      based Medical Expenditure Panel Survey. Using propensity score matching,
      survivors (respondents with prostate cancer history) and controls (respondents
      without a history of any cancer) (N = 193 pairs) were matched based on 7
      sociodemographic and health-related factors. QOL was measured using the mental
      and physical component scores of the SF-12 (SF-36.org). Health status included
      comorbidities, activities of daily living (ADL), instrumental ADL, and depressed
      mood. RESULTS: In bivariate analyses, survivors reported worse physical (42.72 vs
      45.45 respectively; P = .0040) and mental QOL (51.59 vs 53.73 respectively; P =
      .0295) and more comorbidities (3.25 vs 2.78 respectively; P = .0139) than
      controls. In multivariate analyses, for both survivors and controls, better
      physical QOL was associated with fewer comorbidities (P <.0001), no need help
      with ADL (P = .0011) and IADL (P = .0162), and less depressed mood (P <.0001);
      better mental QOL was associated with no need help with IADL (P = .0005) and less
      depressed mood (P <.0001). CONCLUSION: QOL of older men is affected by physical,
      functional, and psychological factors rather than prostate cancer history.
      Clinicians need to attend to aging-related health issues when providing care for
      prostate cancer survivors to improve QOL.

PMID- 24581529
TI  - Re: Lee et al.: Long-term morbidity of Martius labial fat pad graft in vaginal
      reconstruction surgery (Urology 2013;82:1261-1266).

PMID- 24581530
TI  - Reply by the authors.

PMID- 24581531
TI  - Re: Lu et al.: Different cystic fibrosis transmembrane conductance regulator
      mutations in Chinese men with congenital bilateral absence of the vas deferens
      and other acquired obstructive azoospermia (Urology 2013;82:824-828).

PMID- 24581532
TI  - Re: Li et al.: Percutaneous nephrolithotomy under local infiltration anesthesia:
      a single-center experience of 2000 Chinese cases (Urology 2013;82:1020-1025).

PMID- 24581533
TI  - Reply by the authors.

PMID- 24581534
TI  - Reply by the authors.

PMID- 24581535
TI  - Re: Massanyi et al.: Utility of screening ultrasound after first febrile UTI
      among patients with clinically significant vesicoureteral reflux (Urology
      2013;82:905-909).

PMID- 24581536
TI  - Reply by the authors.

PMID- 24581537
TI  - Reply by the authors.

PMID- 24581538
TI  - Re: Cicek et al.: Spinal anesthesia is an efficient and safe anesthetic method
      for percutaneous nephrolithotomy (Urology 2013;83:50-55).

PMID- 24581539
TI  - Higher prevalence of novel mutations in VHL gene in Chinese Von Hippel-Lindau
      disease patients.
AB  - OBJECTIVE: To observe the clinical and molecular characteristics in Chinese Von
      Hippel-Lindau (VHL) disease patients. MATERIALS AND METHODS: Using polymerase
      chain reaction (PCR)-direct sequencing and universal primer quantitative
      fluorescent multiplex-PCR, we examined mutations in VHL gene in 19 VHL disease
      families recruited from the Department of Urology, Peking University First
      Hospital in the period from 2009 to 2012. RESULTS: Of the 19 VHL disease
      families, VHL disease type I was identified in 14 families, type IIA in 1 family,
      and type IIB in 4 families. Mutation detection found missense point mutations in
      7 families, nonsense point mutations in 3 families, small indels in 6 families,
      and large deletions in 3 families. Novel mutations were detected in 9 families
      (47.4%), in which 6 had no family history; previously reported mutations were
      found in 10 families, in which 3 had no family history. CONCLUSION: The
      prevalence of novel mutations without family history was higher in this group of
      patients, presumably demonstrating the higher prevalence of de novo mutations in
      VHL gene in Chinese VHL disease patients.

PMID- 24581540
TI  - Rho-kinase levels in testicular ischemia-reperfusion injury and effects of its
      inhibitor, Y-27632, on oxidative stress, spermatogenesis, and apoptosis.
AB  - OBJECTIVE: To investigate testicular Rho-kinase levels and the effects of its
      inhibitor, Y-27632, on oxidative stress, spermatogenesis, and apoptosis in
      testicular ischemia-reperfusion rat model. METHODS: The study included 29 adult
      Wistar-Albino male rats weighing 150-200 g. The rats were divided into 3 groups.
      Group 1 underwent sham operation (n = 10). In group 2, left testicular torsion
      detorsion was performed (n = 9). In group 3, Rho-kinase inhibitor Y-27632 (5
      mg/kg) was injected intraperitoneally 30 minutes before detorsion (n = 10). Two
      months later, bilateral orchiectomy was performed in all the groups. Rho-kinase
      levels by Western blotting, apoptosis with terminal deoxynucleotidyl transferase
      dUTP nick end labeling method, testicular damage and spermatogenesis with
      modified Johnsen score, testicular total antioxidative status, and total
      oxidative status were measured. RESULTS: In the torsion-detorsion (T/D) group,
      Rho-kinase level increased significantly, compared with the sham group (P =
      .025). In the Y-27632 treatment group, Johnsen scores were significantly higher,
      and apoptosis indexes were significantly lower, compared with the T/D group (P =
      .001). Significantly higher total antioxidative status levels and lower total
      oxidative status levels were observed in the Y-27632 treatment group, compared
      with the T/D group (P = .001 and P = .002, respectively). CONCLUSION: Testicular
      ischemia-reperfusion significantly increased Rho-kinase levels in rats, and
      administration of Rho-kinase inhibitor, Y-27632, before detorsion might prevent
      ischemia-reperfusion injury.

PMID- 24581541
TI  - Editorial comment.

PMID- 24581543
TI  - Effects of chronic treatment with cilostazol, a phosphodiesterase 3 inhibitor, on
      female rat bladder in a partial bladder outlet obstruction model.
AB  - OBJECTIVE: To investigate whether bladder dysfunction after bladder outlet
      obstruction (BOO) could be altered by treatment with cilostazol, a
      phosphodiesterase 3 inhibitor (PDE3i). METHODS: Twelve-week-old female Sprague
      Dawley rats were divided into 5 groups: groups 1 and 2, sham-operated rats and
      groups 3-5, BOO rats. Group 1 and 3 rats were given normal diet, group 2 and 5
      rats were given high-dose PDE3i diet, and group 4 rats were given low-dose PDE3i
      diet. PDE3i was given within diet from the day of surgery. Four weeks after BOO,
      the bladder was excised and dissected into 4 longitudinal strips for isometric
      organ-bath assay. Contractile responses of bladder strips to electrical field
      stimulation (EFS), carbachol, and potassium chloride (KCl) were determined for
      each group. RESULTS: BOO induced a significant increase in bladder weight in
      groups 3-5 compared with groups 1 and 2. PDE3i treatment did not affect bladder
      weight in sham or BOO rats. Contractile forces in response to EFS, carbachol, and
      KCl in group 3 were about 20%-40% of those in group 1. Contractile responses to
      EFS or KCl in PDE3i-treated BOO rats were not significantly different from those
      in group 3. Only high dose of PDE3i treatment in BOO rats caused a statistically
      significant increase in the response to carbachol compared with group 3.
      CONCLUSION: PDE3i has a small but significant protective effect on the
      contractile dysfunction induced by a 4-week BOO in rats, although the increase in
      bladder mass was not altered. PDE3i could be a useful protection against
      contractile dysfunction of the obstructed bladder.

PMID- 24581545
TI  - Acute bladder and small bowel perforation as a complication of Foley
      catheterization.
AB  - The complications of chronic urethral catheterization are well documented in the
      medical published data. Chronic urethral catheterization has been demonstrated to
      cause inflammatory changes within the bladder wall, promoting perforation and
      small bowel fistualization. In this report, we document the clinical course of a
      patient who presented with acute perforation of the bladder and small bowel as a
      result of Foley catheterization. To our knowledge, this is the first documented
      acute perforation of the bladder and the small bowel during Foley
      catheterization. 

PMID- 24581544
TI  - Prolapse of a single system large ureterocele containing multiple stones in a
      pregnant woman.
AB  - Periurethral masses are uncommon in adult women, with little guidance on initial
      management. We describe a case of a 29-year-old pregnant woman with a single
      system ureterocele prolapse complicated by multiple calculi ranging from 1 to 2.5
      cm. 

PMID- 24581546
TI  - Discovery of 2-pyridone derivatives as potent HIV-1 NNRTIs using molecular
      hybridization based on crystallographic overlays.
AB  - Based on crystallographic overlays of the known inhibitors TMC125 and R221239
      complexed in RT, we designed a novel series of 4-phenoxy-6-(phenylamino)pyridin
      2(1H)-one derivatives as HIV NNRTIs by molecular hybridization approach. The
      biological testing results indicated that 2-pyridone scaffold of these inhibitors
      was indispensable for their anti-HIV-1 activity, and substitution of halogen at
      the 3-position of the 2-pyridone ring would decrease the anti-HIV activity. Four
      most potent compounds had anti-HIV-1 IIIB activities at low micromolar
      concentrations (EC50=0.15-0.84 MUM), comparable to that of nevirapine and
      delavidine. Some compounds were selected to test their anti-HIV-1 RT inhibitory
      action and to perform molecular modeling studies to predict the binding mode of
      these 2-pyridone derivatives.

PMID- 24581547
TI  - Interaction kinetics of liposome-incorporated unsaturated fatty acids with fatty
      acid-binding protein 3 by surface plasmon resonance.
AB  - The role of heart-type fatty acid-binding protein (FABP3) in human physiology as
      an intracellular carrier of fatty acids (FAs) has been well-documented. In this
      study, we aimed to develop an analytical method to study real-time interaction
      kinetics between FABP3 immobilized on the sensor surface and unsaturated C18 FAs
      using surface plasmon resonance (SPR). To establish the conditions for SPR
      experiments, we used an FABP3-selective inhibitor 4-(2-(1-(4-bromophenyl)-5
      phenyl-1H-pyrazol-3-yl)-phenoxy)-butyric acid. The affinity index thus obtained
      was comparable to that reported previously, further supporting the usefulness of
      the SPR-based approach for evaluating interactions between FABPs and hydrophobic
      ligands. A pseudo-first-order affinity of FABP3 to K(+) petroselinate (C18:1
      Delta6 cis), K(+) elaidate (C18:1 Delta9 trans), and K(+) oleate (C18:1 Delta9
      cis) was characterized by the dissociation constant (K(d)) near micromolar
      ranges, whereas K(+) linoleate (C18:2 Delta9,12 cis/cis) and K(+) alpha
      linolenate (C18:3 Delta9,12,15 cis/cis/cis) showed a higher affinity to FABP3
      with Kd around 1 * 10(-6)M. Interactions between FAPB3 and C18 FAs incorporated
      in large unilamellar vesicles consisting of 1,2-dimyristoyl-sn-glycero-3
      phosphocholine and FAs (5:1 molar ratio) were also analysed. Control DMPC
      liposomes without FA showed only marginal binding to FABP3 immobilized on a
      sensor chip while liposome-incorporated FA revealed significant responses in
      sensorgrams, demonstrating that the affinity of FAs to FABP3 could be evaluated
      by using the liposome-incorporated analytes. Significant affinity to FABP3 was
      observed for monounsaturated fatty acids (K(d) in the range of 1 * 10(-7)M).
      These experiments demonstrated that highly hydrophobic compounds in a liposome
      incorporated form could be subjected to SPR experiments for kinetic analysis.

PMID- 24581548
TI  - Pseudo-continuous arterial spin labeling MRI study of schizophrenic patients.
AB  - Arterial spin labeling (ASL) magnetic resonance imaging (MRI) is a novel
      noninvasive technique that can measure regional cerebral blood flow (rCBF). To
      our knowledge, few studies have examined rCBF in patients with schizophrenia by
      ASL-MRI. Here we used pseudo-continuous ASL (pCASL) to examine the structural and
      functional imaging data in schizophrenic patients, taking the regional cerebral
      gray matter volume into account. The subjects were 36 patients with schizophrenia
      and 42 healthy volunteers who underwent 3-tesla MRI, diffusion tensor imaging
      (DTI), and pCASL. We evaluated the gray matter volume imaging, DTI, and pCASL
      imaging data in a voxel-by-voxel statistical analysis. The schizophrenia patients
      showed reduced rCBF in the left prefrontal and bilateral occipital cortices
      compared to the healthy volunteers. There was a significant reduction of gray
      matter volume in the left inferior frontal cortex in the schizophrenia patients.
      With respect to the fractional anisotropy (FA) values in the DTI, there were
      significant FA reductions in the left superior temporal, left external capsule,
      and left inferior prefrontal regions in the patients compared to the controls.
      CONCLUSION: Our pCASL study with partial volume effect correction together with
      volumetry and DTI data demonstrated hypoactivity in the left prefrontal area
      beyond structural abnormalities in schizophrenia patients. There were also
      hypofunction areas in bilateral occipital cortices, although structural
      abnormalities were not apparent.

PMID- 24581549
TI  - Genetic modifiers and subtypes in schizophrenia: investigations of age at onset,
      severity, sex and family history.
AB  - Schizophrenia is a genetically and clinically heterogeneous disorder. Genetic
      risk factors for the disorder may differ between the sexes or between multiply
      affected families compared to cases with no family history. Additionally, limited
      data support a genetic basis for variation in onset and severity, but specific
      loci have not been identified. We performed genome-wide association studies
      (GWAS) examining genetic influences on age at onset (AAO) and illness severity as
      well as specific risk by sex or family history status using up to 2762 cases and
      3187 controls from the International Schizophrenia Consortium (ISC). Subjects
      with a family history of schizophrenia demonstrated a slightly lower average AAO
      that was not significant following multiple testing correction (p=.048), but no
      differences in illness severity were observed by family history status (p=.51).
      Consistent with prior reports, we observed earlier AAO (p=.005) and a more severe
      course of illness for men (p=.002). Family history positive analyses showed the
      greatest association with KIF5C (p=1.96*10(-8)), however, genetic risk burden
      overall does not differ by family history. Separate association analyses for
      males and females revealed no significant sex-specific associations. The top GWAS
      hit for AAO was near the olfactory receptor gene OR2K2 (p=1.52*10(-7)). Analyses
      of illness severity (episodic vs. continuous) implicated variation in ST18
      (p=8.24*10(-7)). These results confirm recognized demographic relationships but
      do not support a simplified genetic architecture for schizophrenia subtypes based
      on these variables. 

PMID- 24581551
TI  - Jumping to perceptions and to conclusions: specificity to hallucinations and
      delusions.
AB  - BACKGROUND: There is evidence that people with psychosis display a "jump-to
      conclusions" (JTC) reasoning style, and that this bias may be specific to
      delusions. A "jump-to-perceptions" (JTP) cognitive bias has also been found and
      is typically linked to hallucinations. However, there is some evidence for an
      association between JTP and delusions, and its specificity to hallucinations
      remains unclear. It has been suggested that these biases are related and products
      of shared cognitive processes. METHODS: This study examined the symptom
      specificity of JTC and JTP, and the relationship between them, in a sample of 98
      individuals with delusions divided into 'hallucinators' (n=51) and 'non
      hallucinators' (n=47). Biases were assessed using the beads task and visual and
      auditory perceptual tasks. RESULTS: As predicted, both groups demonstrated a JTC
      bias, but the 'hallucinators' showed a more pronounced JTP style in both
      modalities. The presence of JTC and JTP biases did not co-occur: making a
      decision on the beads task after two or fewer draws was not related to visual
      JTP, and was associated with a less marked JTP bias in the auditory perceptual
      task. No differences were found in JTP or JTC between participants with and
      without a schizophrenia diagnosis. JTP, but not JTC, was associated with the
      presence of hallucinations. CONCLUSIONS: These findings suggest that the JTC and
      JTP biases show specificity to delusions and hallucinations, respectively, and
      not to diagnosis. There was no evidence that they are the product of shared
      cognitive processes, further supporting their specificity.

PMID- 24581550
TI  - The relationship between suicide and violence in schizophrenia: analysis of the
      Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) dataset.
AB  - BACKGROUND: Suicide and violence often co-occur in the general population as well
      as in mentally ill individuals. Few studies, however, have assessed whether these
      suicidal behaviors are predictive of violence risk in mental illness. AIMS: The
      aim of this study is to investigate whether suicidal behaviors, including
      suicidal ideation, threats, and attempts, are significantly associated with
      increased violence risk in individuals with schizophrenia. METHOD: Data for these
      analyses were obtained from the Clinical Antipsychotic Trials of Intervention
      Effectiveness (CATIE) trial, a randomized controlled trial of antipsychotic
      medication in 1460 adults with schizophrenia. Univariate Cox regression analyses
      were used to calculate hazard ratios (HRs) for suicidal ideation, threats, and
      attempts. Multivariate analyses were conducted to adjust for common confounding
      factors, including: age, alcohol or drug misuse, major depression, antisocial
      personality disorder, depression, hostility, positive symptom, and poor impulse
      control scores. Tests of discrimination, calibration, and reclassification
      assessed the incremental predictive validity of suicidal behaviors for the
      prediction of violence risk. RESULTS: Suicidal threats and attempts were
      significantly associated with violence in both males and females with
      schizophrenia with little change following adjustment for common confounders.
      Only suicidal threats, however, were associated with a significant increase in
      incremental validity beyond age, diagnosis with a comorbid substance use
      disorder, and recent violent behavior. CONCLUSIONS: Suicidal threats are
      independently associated with violence risk in both males and females with
      schizophrenia, and may improve violence risk prediction.

PMID- 24581552
TI  - Prevalence of Dirofilaria immitis among shelter dogs in Tokyo, Japan, after a
      decade: comparison of 1999-2001 and 2009-2011.
AB  - Changes in the seroprevalence of Dirofilaria immitis infection among shelter dogs
      between a decade ago and the present were evaluated. Serum samples were collected
      from 200 adult dogs in urban and suburban areas in Tokyo, Japan, during two 2
      year periods (April 1999 to March 2001 and April 2009 to March 2011). Sera were
      tested for the presence of D. immitis antigen using a specific commercialized
      kit. The seroprevalence of D. immitis infection was 46% in 1999-2001 and 23% in
      2009-2011. A decrease was observed in the prevalence of infection between 1999
      2001 and 2009-2011; in particular, the prevalence in urban areas decreased
      significantly compared with that in suburban areas (P < 0.01). There was no
      significant difference in prevalence between the sexes in each period, but there
      was a significant difference between mixed-breed and purebred dogs (P < 0.01).
      The decrease in prevalence of canine heartworm disease in urban areas could be
      related to better veterinary care.

PMID- 24581553
TI  - Posterior reversible encephalopathy syndrome (PRES) complicating newly-diagnosed
      diffuse large B-cell lymphoma.

PMID- 24581554
TI  - Neurophysiological aspects of neonatal seizures.
AB  - Recently, amplitude-integrated EEG (aEEG) has been increasingly used and proved
      useful in neonatal intensive care units (NICU) for the management of neonatal
      seizures. It does not replace, but is supplementary to standard EEG. This article
      reviews some of findings obtained with standard EEGs, and tries to interpret them
      with recent findings in the field of basic science. Seizures mainly occur in
      active-REM sleep in neonates. This is in sharp contrast to those in older
      children and adults, in whom epileptic seizures occur mainly in NREM sleep. This
      may be explained by neurotransmitter effects on sleep mechanisms of the neonatal
      brain that are different from those of older individuals. When all clinical
      seizures have no electrical correlates, they are non-epileptic, but when the
      correlation between clinical seizures and frequent electrical discharges are
      inconsistent, they should rather be considered epileptic, reflecting progression
      of status epilepticus causing electro-clinical dissociation. Electro-clinical
      dissociation is not a characteristic of neonatal seizures per se, but a feature
      of prolonged status epilepticus in adults as well as children. It occurs when
      prolonged status epilepticus itself causes a progressively severe encephalopathy,
      or when status occurs in the presence of a severe underlying encephalopathy. In
      neonates without pre-existing brain damage, frequent seizures per se may cause
      mild depression characterized by the loss of high voltage slow patterns, an
      important constituent of slow wave sleep reflecting cortico-cortical
      connectivity. Mild depression only in the acute stage is not associated with
      neurological sequelae, but previously damaged brain may be more vulnerable than
      normal brain. 

PMID- 24581555
TI  - A comprehensive evaluation of assembly scaffolding tools.
AB  - BACKGROUND: Genome assembly is typically a two-stage process: contig assembly
      followed by the use of paired sequencing reads to join contigs into scaffolds.
      Scaffolds are usually the focus of reported assembly statistics; longer scaffolds
      greatly facilitate the use of genome sequences in downstream analyses, and it is
      appealing to present larger numbers as metrics of assembly performance. However,
      scaffolds are highly prone to errors, especially when generated using short
      reads, which can directly result in inflated assembly statistics. RESULTS: Here
      we provide the first independent evaluation of scaffolding tools for second
      generation sequencing data. We find large variations in the quality of results
      depending on the tool and dataset used. Even extremely simple test cases of
      perfect input, constructed to elucidate the behaviour of each algorithm, produced
      some surprising results. We further dissect the performance of the scaffolders
      using real and simulated sequencing data derived from the genomes of
      Staphylococcus aureus, Rhodobacter sphaeroides, Plasmodium falciparum and Homo
      sapiens. The results from simulated data are of high quality, with several of the
      tools producing perfect output. However, at least 10% of joins remains
      unidentified when using real data. CONCLUSIONS: The scaffolders vary in their
      usability, speed and number of correct and missed joins made between contigs.
      Results from real data highlight opportunities for further improvements of the
      tools. Overall, SGA, SOPRA and SSPACE generally outperform the other tools on our
      datasets. However, the quality of the results is highly dependent on the read
      mapper and genome complexity.

PMID- 24581557
TI  - Color synesthesia improves color but impairs motion perception.
AB  - A recent study showed that color synesthetes have increased color sensitivity but
      impaired motion perception. This is exciting because little research has examined
      how synesthesia affects basic perceptual processes outside the context of
      synesthetic experiences. The results suggest that synesthesia broadly impacts
      perception with greater neural implications than previously considered. 

PMID- 24581558
TI  - Chagas disease: the challenge of polyparasitism?
AB  - The debilitating zoonosis Chagas disease (CD) is caused by infection with the
      flagellate protozoan Trypanosoma cruzi. One century after its discovery, a
      curative agent remains elusive. Immune evasion by T. cruzi results in a poorly
      controlled infection in the host, which can end in either sudden death or a fatal
      chronic disease that often eventuates after years of an asymptomatic infection.
      Polyparasitism or mixed/concurrent infections occur more often than not and
      contribute to the high degree of variability observed across both disease
      progression and the success of therapeutic interventions. A thorough
      understanding of the effects of polyparasitism on CD is essential for improving
      the likelihood of containing, treating, and eventually eliminating CD. 

PMID- 24581556
TI  - Action versus valence in decision making.
AB  - The selection of actions, and the vigor with which they are executed, are
      influenced by the affective valence of predicted outcomes. This interaction
      between action and valence significantly influences appropriate and inappropriate
      choices and is implicated in the expression of psychiatric and neurological
      abnormalities, including impulsivity and addiction. We review a series of recent
      human behavioral, neuroimaging, and pharmacological studies whose key design
      feature is an orthogonal manipulation of action and valence. These studies find
      that the interaction between the two is subject to the critical influence of
      dopamine. They also challenge existing views that neural representations in the
      striatum focus on valence, showing instead a dominance of the anticipation of
      action. 

PMID- 24581559
TI  - Assessment of early onset of driver fatigue using multimodal fatigue measures in
      a static simulator.
AB  - Driver fatigue is an important contributor to road accidents. This paper reports
      a study that evaluated driver fatigue using multimodal fatigue measures, i.e.,
      surface electromyography (sEMG), electroencephalography (EEG), seat interface
      pressure, blood pressure, heart rate and oxygen saturation level. Twenty male
      participants volunteered in this study by performing 60 min of driving on a
      static simulator. Results from sEMG showed significant physical fatigue (rho <
      0.05) in back and shoulder muscle groups. EEG showed significant (rho < 0.05)
      increase of alpha and theta activities and a significant decrease of beta
      activity during monotonous driving. Results also showed significant change in
      bilateral pressure distribution on thigh and buttocks region during the study.
      These findings demonstrate the use of multimodal measures to assess early onset
      of fatigue. This will help us understand the influence of physical and mental
      fatigue on driver during monotonous driving.

PMID- 24581560
TI  - Evaluation of the facelift patient.

PMID- 24581561
TI  - Surgical anatomy of the superficial musculo-aponeurotic system (SMAS).

PMID- 24581562
TI  - Management of the superficial musculo-aponeurotic system (SMAS).

PMID- 24581563
TI  - Rejuvenation of the anterior neck: the when and why.

PMID- 24581564
TI  - Short scar rhytidectomy techniques.

PMID- 24581565
TI  - The opportunistic rhytidectomy: the biplane facelift.

PMID- 24581566
TI  - Combined rhytidectomy and alloplastic facial implants.

PMID- 24581567
TI  - Adjunctive techniques in contemporary rhytidectomy.

PMID- 24581568
TI  - Reoperative face and neck lifts.

PMID- 24581569
TI  - Contemporary rhytidectomy.

PMID- 24581570
TI  - Effect of inhalation exposure to wheat flour on sputum levels of brain-derived
      neurotrophic factor.

PMID- 24581571
TI  - Reply to: lack of prognostic significance of conventional peritoneal cytology in
      colorectal and gastric cancers: results of EVOCAPE 2 multicentre prospective
      study.

PMID- 24581573
TI  - Evaluation of the diagnostic criteria of Internet gaming disorder in the DSM-5
      among young adults in Taiwan.
AB  - The DSM-5 proposed the diagnostic criteria of Internet gaming disorder (IGD) and
      suggested that more evidence is necessary before it is included as a standard
      disorder in the DSM system. The aims of this study were to: 1) evaluate the
      diagnostic validity of individual criteria of IGD in the DSM-5 and the criteria
      of craving and irritability; 2) determine the optimal cut-off point for the IGD
      criteria in the DSM-5. We recruited 75 subjects with IGD, 75 without IGD, and 75
      in remission from IGD based on the Diagnostic Criteria of Internet Addiction for
      College Students (DC-IA-C). All participants underwent a diagnostic interview
      based on the diagnostic criteria of IGD in the DSM-5 and completed the CIAS and
      QGU-B. Except for the "deceiving" and "escape" criteria, all criteria of IGD had
      diagnostic accuracy ranging from 77.3% to 94.7% to differentiate university
      students with IGD from remitted students. The criterion of craving had diagnostic
      accuracy of 88% and the criteria of irritability had an accuracy of 68.7%.
      Fulfilling 5 or more criteria of IGD in the DSM-5 was the best cut-off point to
      differentiate young adults with IGD from healthy or remitted users. 

PMID- 24581572
TI  - The role of common mental and physical disorders in days out of role in the Iraqi
      general population: results from the WHO World Mental Health Surveys.
AB  - In an effort to support mental health policy planning efforts in conjunction with
      the reconstruction of Iraq, a nationally representative face-to-face household
      survey was carried out that assessed the prevalence and correlates of common
      mental disorders in the Iraqi population. A total of 4332 adult (ages 18+)
      respondents were interviewed (95.2% response rate). The current report presents
      data on the role impairments (number of days out-of-role in the past 30 days)
      associated with the nine mental disorders assessed in the survey in comparison to
      the impairments associated with ten chronic physical disorders also assessed in
      the survey. These disorders were all assessed with the WHO Composite
      International Diagnostic Interview. Days out-of-role were assessed with the WHO
      Disability Assessment Schedule. Both individual-level and societal-level effects
      of the disorders were estimated. Strongest individual-level predictors were
      bipolar and drug abuse disorders (176-195 days per year), with mental disorders
      making up five of the seven strongest predictors. The strongest population-level
      predictors were headache/migraine and arthritis (22-12% population proportions).
      Overall population proportions were 57% of days out-of-role due to the chronic
      physical disorders considered here and 18% for the mental disorders. Despite
      commonly-occurring mental disorders accounting for more individual-level days out
      of-role than the physical disorders, mental disorders are much less likely to
      receive treatment in Iraq (e.g., due to stigma). These results highlight the need
      for culturally tailored mental health prevention and treatment programs in Iraq. 

PMID- 24581574
TI  - A retrospective cohort study to evaluate the impact of meaningful weight loss on
      fertility outcomes in an overweight population with infertility.
AB  - OBJECTIVE: To determine if meaningful weight loss (>=10%) improved conception and
      live birth rates of overweight patients with infertility. DESIGN: A retrospective
      cohort study. SETTING: Academic medical center. PATIENT(S): Overweight patients
      (body mass index >=25 kg/m(2); n = 52) being treated for infertility and referred
      for weight loss counseling. INTERVENTION(S): Patients were given a "meaningful"
      weight loss goal of 10%. They were followed by an endocrinologist who provided
      diet and exercise recommendations, metabolic screening, and pharmacologic
      intervention when indicated. MAIN OUTCOME MEASURE(S): Pregnancy rate, live birth
      rate, weight loss. RESULT(S): Thirty-two percent of the patients achieved
      meaningful weight loss. Patients achieving meaningful weight loss had
      significantly higher conception (88% vs. 54%) and live birth rates (71% vs. 37%)
      than those who did not. CONCLUSION(S): Weight loss improves live birth rates in
      overweight patients with infertility. Health care providers should incorporate
      weight loss counseling when caring for overweight patients who plan to conceive.

PMID- 24581576
TI  - Diagnostic accuracy of three-dimensional sonohysterography compared with office
      hysteroscopy and its interrater/intrarater agreement in uterine cavity assessment
      after hysteroscopic metroplasty.
AB  - OBJECTIVE: To compare the diagnostic accuracy of three-dimensional
      sonohysterography (3D-SIS) and office hysteroscopy in uterine cavity assessment
      after hysteroscopic metroplasty (HM) and determine the interrater/intrarater
      agreement for 3D-SIS. DESIGN: Prospective observational study. SETTING:
      University hospital, private hospital, and clinic. PATIENT(S): One hundred forty
      one women undergoing HM for septate uterus with a history of miscarriage and/or
      infertility. INTERVENTION(S): 3D-SIS and office hysteroscopy at 6-8 weeks after
      HM. MAIN OUTCOME MEASURE(S): Shape of the uterine cavity, length of the fundal
      notch (>=1 or <1 cm), and the presence of intrauterine adhesions were assessed,
      and the interrater/intrarater agreement of 3D-SIS was evaluated in 30 randomly
      selected patients. RESULT(S): Uterine abnormalities were detected with the use of
      hysteroscopy in 18 (12.8%) of 141 women. 3D-SIS was highly accurate (97.2%),
      sensitive (97%), and specific (100%), with a positive predictive value of 100%
      and a negative predictive value of 85%. The diagnostic values of hysteroscopy and
      3D-SIS were not significantly different (McNemar test). 3D-SIS showed substantial
      interrater/intrarater agreement regarding overall uterine cavity evaluation
      (kappa = 0.79 and 0.78, respectively). CONCLUSION(S): 3D-SIS demonstrated
      substantial interrater/intrarater agreement for the postoperative evaluation of
      the uterine cavity, being as diagnostically accurate as hysteroscopy. The use of
      second-look hysteroscopy may be limited to cases that require reoperation.

PMID- 24581575
TI  - Gonadal dysfunction in morbidly obese adolescent girls.
AB  - OBJECTIVE: To describe gonadal dysfunction and evaluate polycystic ovary syndrome
      (PCOS) and its association with metabolic syndrome (MeS) among girls in a
      morbidly obese adolescent population. DESIGN: In a cross-sectional study of 174
      girls, height, weight, waist circumference, Tanner stage, reproductive hormones,
      carbohydrate and lipid markers, drug use, and menstrual history were obtained at
      baseline. Exclusion criteria were menarcheal age <2 years, hormonal contraceptive
      or metformin use, Tanner stage <4, and incomplete data on PCOS or MeS
      classification. SETTING: University medical center outpatient clinic. PATIENT(S):
      Ninety-eight girls ages 13-19.6 years, Tanner 5, average body mass index of 46.6
      kg/m(2), menarche at 11.4 years, and average menarcheal age of 5 years.
      INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Polycystic ovary syndrome and
      MeS. RESULT(S): Ninety-eight girls were divided into four groups: PCOS by
      National Institutes of Health criteria (PCOSN, n = 24), irregular menses only (n
      = 25), elevated T (>=55 ng/dL) only (n = 6), and obese controls (n = 43).
      Metabolic syndrome by modified Cook criteria affected 32 girls or 33% overall: 6
      of 24 PCOSN, 7 of 25 irregular menses only, 4 of 6 elevated T only, and 15 of 43
      obese controls. Polycystic ovary syndrome by National Institutes of Health
      criteria and its individual components were not associated with MeS after
      adjusting for body mass index. CONCLUSION(S): Unlike obese adults, PCOSN and its
      individual components were not associated with MeS in the untreated morbidly
      obese adolescent population.

PMID- 24581577
TI  - Generation of multi-oocyte follicles in the peripubertal rat ovary: link to the
      invasive capacity of granulosa cells?
AB  - OBJECTIVE: To assess the presence and numbers of multi-oocyte follicles (MOFs) in
      the rat ovary at different stages of postnatal maturation. DESIGN: Animal (rat)
      study. SETTING: Research laboratory. ANIMAL(S): Female Wistar rats.
      INTERVENTION(S): Histologic/morphometric analyses in ovaries from infantile,
      juvenile, pubertal, and adult female rats. MAIN OUTCOME MEASURE(S): Numbers and
      characteristics of MOFs in rat ovaries at different stages of postnatal
      maturation. RESULT(S): Female rats displayed low numbers (<5/ovary) of MOFs in
      the infantile period (postnatal day [PND] 15). The occurrence of MOFs increased
      sharply by PND-21 and remained at high values (>15/ovary) up to PND-60, to
      decline thereafter by PND-90. The presence of irregularly shaped and connected
      adjacent follicles, together with the identification of ruptures at the follicle
      surface and the occasional invasion of the ovarian stroma by granulosa cells,
      strongly suggests that the majority of MOFs in peripubertal rats are generated by
      fusion of adjacent growing follicles. CONCLUSION(S): A new mechanism for the
      generation of MOFs linked to the potential invasive capacity of granulosa cells
      is proposed. The basis for the upsurge in the generation of MOFs during the
      peripubertal period and whether, as predictable, this phenomenon is applicable to
      other mammalian species warrant further investigation.

PMID- 24581578
TI  - Variability in the components of high-density lipoprotein particles measured in
      human ovarian follicular fluid: a cross-sectional analysis.
AB  - OBJECTIVE: To assess the variability of follicular fluid (FF) high-density
      lipoprotein (HDL) particle components. DESIGN: Cross-sectional design with
      assessment using two-stage nested analysis of variance. SETTING: Reproductive
      health center. PATIENT(S): 180 in vitro fertilization (IVF) patients.
      INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Nineteen HDL components including
      HDL cholesterol and free (unesterified) and esterified forms, phospholipids,
      triglycerides, apolipoproteins A-1 and A-2, paraoxonase 1 (PON1) activities, and
      seven lipophilic vitamins and micronutrients. RESULT(S): We collected FF
      specimens from two contralateral follicles on the day of oocyte retrieval and
      analyzed them for HDL components, characterizing the analytes by age, body mass
      index (BMI), race and smoking. For some analytes, a majority of total measurement
      variability was attributed to sources between follicles, suggesting an important
      role for the integrity of the blood-follicle barrier and in situ remodeling of
      plasma-derived constituents. For other analytes, variability was mostly
      attributed to sources between women, likely indicative of plasma levels.
      Variability between follicles decreased with increasing age and differed by BMI
      and smoking, and generally were lower for Asians and women with diminished
      ovarian reserve. CONCLUSION(S): Substantial variability in FF HDL components
      exist between follicles among women undergoing IVF as well as between women by
      age, BMI, race, smoking, and infertility diagnosis.

PMID- 24581580
TI  - Perinatal outcome of twin pregnancies after early transvaginal multifetal
      pregnancy reduction.
AB  - OBJECTIVE: To compare the pregnancy outcomes of twin pregnancies following early
      transvaginal multifetal pregnancy reduction (MPR) with nonreduced twin
      gestations. DESIGN: Prospective cohort study. SETTING: Two tertiary medical
      centers. PATIENT(S): A cohort of 77 multiple pregnancies after reduction to twins
      and 78 dichorionic-diamniotic nonreduced twins. INTERVENTION(S): Early fetal
      reduction. MAIN OUTCOME MEASURE(S): Pregnancy outcome. RESULT(S): Triplet
      pregnancies reduced to twins (n = 55) and nonreduced twin pregnancies (n = 78)
      had comparable outcomes. The rates of preterm delivery <=32 weeks (1.9% vs. 1.4%)
      and <=34 weeks of gestation (15.1% vs. 19.2%) were similar among both groups.
      There was no difference in the mean gestational age (36.54 vs. 36.35 weeks) or
      mean birth weight (2,365 vs. 2,365 g) between the two groups. Similarly, there
      was no significant difference in the incidence of gestational diabetes (15.1% vs.
      14.1%) and intrauterine growth retardation (IUGR; 1.9% vs. 9%) between the two
      groups. The incidence of gestational hypertension was higher in the study group
      (24.5% vs. 9%), but it was not associated with an increased risk for prematurity
      or IUGR. CONCLUSION: The perinatal outcome of twin pregnancies after early
      transvaginal fetal reduction from triplets seems to be comparable to the outcome
      of nonreduced twin pregnancies.

PMID- 24581579
TI  - Dopamine receptor 2 activation inhibits ovarian vascular endothelial growth
      factor secretion in vitro: implications for treatment of ovarian hyperstimulation
      syndrome with dopamine receptor 2 agonists.
AB  - OBJECTIVE: To ascertain whether vascular endothelial growth factor (VEGF)
      secretion by luteinized granulosa cells (GCs) is modulated by the dopaminergic
      system in a dose-dependent fashion and how this is related to the differential
      efficacy of dopamine receptor 2 (D2)-agonists (D2-ag) in preventing ovarian
      hyperstimulation syndrome (OHSS). DESIGN: The relationship between the
      dopaminergic system and VEGF secretion in luteinized GCs was evaluated. Archived
      human ovaries were immunostained to characterize D2 expression. SETTING:
      University affiliated infertility center. PATIENT(S): Premenopausal women and egg
      donors. INTERVENTION(S): Luteinized GCs were cultured with the D2-ag cabergoline.
      Human ovarian sections were immunostained for D2. MAIN OUTCOME MEASURE(S): The
      VEGF was measured by ELISA and D2 expression was evaluated by In-Cell ELISA. The
      D2 expression throughout the luteal phase was characterized by
      immunohistochemistry. RESULT(S): The VEGF secretion was decreased by the D2-ag in
      a dose-dependent fashion. The efficiency of this process was correlated with the
      amount of D2 expressed by luteinized GCs. A decrease in D2 expression in ovarian
      sections was observed during the late luteal phase. CONCLUSION(S): The efficacy
      of D2-ags in preventing OHSS might rely on their capacity to inhibit VEGF
      secretion by luteinized GCs. Because this capacity is dose-dependent, increasing
      the intraovarian concentration of D2-ags should be explored as a means of
      increasing the efficacy of these drugs in preventing OHSS.

PMID- 24581582
TI  - Eliminating acute lymphoblastic leukemia cells from human testicular cell
      cultures: a pilot study.
AB  - OBJECTIVE: To study whether acute lymphoblastic leukemia (ALL) cells survive in a
      human testicular cell culture system. DESIGN: Experimental laboratory study.
      SETTING: Reproductive biology laboratory, academic medical center. PATIENT(S):
      Acute lymphoblastic leukemia cells from three patients and testicular cells from
      three other patients. INTERVENTION(S): Acute lymphoblastic leukemia cells were
      cultured alone or in combination with testicular cells, at various
      concentrations, in a system that has recently been developed to propagate human
      spermatogonial stem cells. MAIN OUTCOME MEASURE(S): Viability of ALL and
      testicular cells during culture was evaluated by flow cytometry using markers for
      live/dead cells. Furthermore, the presence of ALL cells among testicular cells
      was determined by highly sensitive (1:10,000 to 1:100,000 cells) patient-specific
      antigen-receptor minimal residual disease polymerase chain reaction. The presence
      of spermatogonia at the end of culture was determined by reverse transcription
      polymerase chain reaction for ZBTB16, UCHL1, and GPR125. RESULT(S): The ALL cells
      cultured separately did not survive beyond 14 days of culture. When cultured
      together with testicular cells, even at extremely high initial concentrations
      (40% ALL cells), ALL cells were undetectable beyond 26 days of culture. Reverse
      transcription-polymerase chain reaction confirmed the presence of spermatogonia
      at the end of the culture period. CONCLUSION(S): Our pilot study shows that the
      described testicular cell culture system not only allows for efficient
      propagation of spermatogonial stem cells but also eliminates contaminating ALL
      cells.

PMID- 24581581
TI  - Urinary cytokine and chemokine profiles across the menstrual cycle in healthy
      reproductive-aged women.
AB  - OBJECTIVE: To assess the utility of urinary cytokines for monitoring reproductive
      function by considering detection, variation across the menstrual cycle, and
      relations with hormones. DESIGN: Longitudinal cohort study. SETTING: Academic
      institution. PATIENT(S): Healthy, reproductive-aged women with self-reported
      regular menstrual cycles and at least one observed ovulatory cycle (n = 248).
      INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Urinary cytokines measured by 30
      plex immunoassays in 3,550 biospecimens, and nested random-effects analysis of
      variance (ANOVA) and marginal structural models used to evaluate variability and
      relations with hormones. RESULT(S): For 24 of 30 evaluated factors, detectable
      levels were observed in at least 50% of urine samples. Interleukin-6 (IL-6), IL
      8, IL-10, IL-15, granulocyte colony stimulating factor (G-CSF), hepatocyte growth
      factor (HGF), interferon-alpha (IFN-alpha), and RANTES (regulated upon activation
      normal T-cell expressed and secreted) levels varied significantly across the
      menstrual cycle. The proinflammatory factors IL-1beta, IL-6, IL-8, and HGF were
      1.5-3 times higher during menses than the late follicular phase. In marginal
      structural models, IL-1beta, IL-6, IL-8 were associated with lower estradiol and
      progesterone concentrations. CONCLUSION(S): Variability during the menstrual
      cycle and correlations with reproductive hormone levels support a role of
      cytokines in the menstrual cycle; however, because of the limited variability for
      most cytokines considered, the utility of urine as a matrix for assessment of
      inflammation in menstrual cycle function appears limited for clinical purposes.

PMID- 24581583
TI  - Gene expression analysis of bovine oocytes at optimal coasting time combined with
      GnRH antagonist during the no-FSH period.
AB  - Ovarian stimulation with FSH combined with an appropriate period of FSH
      withdrawal (coasting) before ovum pick-up now appears to be a successful way to
      obtain oocytes with high developmental competence in bovine. Recent results
      showed that extending follicular growth by only 24 hours has a detrimental effect
      on oocyte quality as shown by the reduced blastocyst formation rate. Although
      these treatments are initiated during the luteal phase with low LH level, the
      small LH pulsatility present at that time could potentially impact follicular
      development as well as oocyte quality. In this study, a GnRH antagonist
      (Cetrotide) was used to suppress LH secretion during follicular differentiation
      to get a better insight into the physiological importance of the LH support
      during that period. Oocytes were collected by ovum pick-up, and quality was
      assessed by measuring the blastocyst formation rate obtained after IVM-IVF. The
      oocyte transcriptome from GnRH antagonist-treated animals was also compared with
      that from a control group (coasting duration of 68 hours) to detect possible
      alterations at the messenger RNA (mRNA) level. The oocyte quality was not
      statistically affected by the treatment as shown by the blastocyst formation rate
      obtained. However, microarray analysis showed that a total of 226 genes had a
      significant difference (fold change > 2; P < 0.05) at the mRNA level, with the
      majority being in overabundance in the treated group. Many genes related to RNA
      posttranscriptional modifications presented different abundance at the mRNA level
      significant differences in the control group (68 hours), whereas translation
      function appeared to be affected, with many genes related to structural
      constituents of the ribosome presenting a overabundance in the GnRH antagonist
      treated group. Specific mRNAs with crucial roles in chromosome segregation
      control also showed significant difference at the mRNA level after Cetrotide
      treatment. The results presented here indicated that the suppression of the LH
      secretion in an optimal stimulated context would have an impact on the oocyte,
      with the possible alteration of critical functions related to translation
      capacity and chromosome segregation control.

PMID- 24581584
TI  - Evaluation of sperm subpopulation structure in relation to in vitro sperm-oocyte
      interaction of frozen-thawed semen from Holstein bulls.
AB  - The present study examined the relationship between the relative amount of high
      motile sperm and sperm-oocyte interactions obtained from Holstein bull
      ejaculates. Post-thaw sperm motility was analyzed using a computer-assisted sperm
      analyzer system and evaluated to determine the sperm motility subpopulations.
      Adhesion and penetration of zona pellucida (ZP) and pronucleus formation using
      post-thawed samples (15 ejaculates form 5 different bulls) with different
      percentages of sperm in the subpopulation with the fastest and most progressive
      subpopulation (subpopulation 4 [SP4]) were analyzed. The correlation between the
      proportion of sperm in SP4 and the number of spermatozoa bound to the zona
      pellucida (ZBA), the penetration rate, and the rate of pronucleus formation were
      calculated. A significant (P < 0.05) and positive correlation was found between
      the number of spermatozoa bound to the zona pellucida, the penetration rate, and
      the rate of pronucleus formation with the proportion of sperm in SP4 (r = 0.79, r
      = 0.66, and r = 0.63, respectively). Our results suggest that this specific high
      motile and progressive subpopulation is positively and significantly correlated
      with the ability of a thawed bull semen sample to interact properly with the
      oocyte and its extracellular vestments. These findings emphasize the relevance of
      analyzing semen subpopulation composition to predict bull sperm fertilizing
      ability and to select Holstein bulls for breeding purposes. 

PMID- 24581585
TI  - Effect of xylazine, isoxsuprine, and lidocaine on Doppler sonographic uterine and
      umbilical blood flow measurements in cows during the last month of pregnancy.
AB  - The maternal portion of the bovine placenta receives blood mainly from the
      uterine arteries (AUT) and the fetal portion from the umbilical arteries (AUM).
      Placental perfusion is crucial for fetal development and undergoes adaptive
      changes during pregnancy according to the fetal requirements. One goal of this
      study was to investigate changes in Doppler sonographic measurements of blood
      vessels that supply blood to the placenta in cows during the last 4 weeks of
      pregnancy. Another goal was to examine how these measurements are affected by
      three drugs commonly used in cows at the time of parturition. Nine cows underwent
      Doppler sonographic examination of the AUT ipsilateral and contralateral to the
      pregnant horn and one AUM three times per week during the last 4 weeks of
      gestation. This was followed by the randomized administration of one of the three
      following experimental drugs per day: isoxsuprine (200 mg/cow, iv), xylazine (2
      mg/100 kg, iv), and lidocaine for epidural anesthesia (100 mg/cow). Doppler
      sonographic examination was repeated 30 minutes after medication. Maternal pulse
      rate increased during the study period (P < 0.001), and the diameter of the
      contralateral AUT was smaller in the last week before birth than in the two
      preceding weeks. The resistance index (RI) of the ipsilateral AUT was smaller in
      the last week than in the first 2 weeks of the study period. Uterine blood flow
      volume increased after isoxsuprine by 5% and after epidural anesthesia by 6%
      (both P <= 0.05) and decreased after xylazine by 10% (P < 0.001). Isoxsuprine was
      the only drug that elevated the blood flow volume in the AUM (P <= 0.05).
      Xylazine increased the RI of both AUT (both P < 0.001) and significantly reduced
      maternal and fetal pulse frequencies, whereas isoxsuprine significantly reduced
      the RI of both AUT and the AUM and increased maternal and fetal pulse
      frequencies. The results reported that Doppler sonographic measurements of
      uterine and AUM change little in the last month of pregnancy in the cow.
      Isoxsuprine and epidural anesthesia with lidocaine have the potential to improve
      uterine perfusion. 

PMID- 24581586
TI  - Reversibility of germinative and endocrine testicular function after long-term
      contraception with a GnRH-agonist implant in the tom-a follow-up study.
AB  - A significantly reduced gonadotropin and testosterone secretion is a well
      described result of long-term administration of GnRH agonists in the male dog and
      cat. To date, no data are available about the duration of efficacy and the
      reversibility of treatment-induced effects after long-term treatment with a 4.7
      mg deslorelin implant. Seven healthy male European Shorthair cats (3.2 +/- 0.5
      kg, 1-6 years) were treated with a 4.7 mg deslorelin implant. Blood samples
      (testosterone, T), testicular volume, penile spines, and mating behavior were
      recorded once weekly. Considering T > 0.5 ng/mL as the biological endpoint, mean
      duration of efficacy was 78.8 +/- 12.9 weeks (range: 61.7-100.7 weeks) with T
      concentrations increasing rapidly after the last T less than 0.1 ng/mL (basal) (P
      < 0.0001), and pretreatment T concentrations being reached after 3 weeks.
      Testicular volume rapidly increased after the first increase of T (P < 0.001)
      with pretreatment testicular volume being reached after 6.9 +/- 3.4 weeks (5-11
      weeks). "Normal" libido reoccurred 88.7 +/- 12.4 weeks after treatment, and
      "normal" mating behavior was observed even later. Fertile matings occurred 7 to
      42 weeks after the last T less than 0.1 ng/mL with a mean of 4.0 +/- 0.0 kittens,
      and 13.6 to 47.6 weeks afterwards testicular histology revealed normal
      spermatogenesis. The present data confirm that the use of slow-release GnRH
      agonist implants containing deslorelin in tomcats represents an effective and
      safe reversible alternative for long-term contraception; however, as number of
      animals is low, further fertility trials are recommended. 

PMID- 24581587
TI  - Enhancement of maternal recognition of pregnancy with parthenogenetic embryos in
      bovine embryo transfer.
AB  - This study was performed to elucidate the changes in IFNT messenger RNA (mRNA)
      levels in in vivo-fertilized and parthenogenetic bovine embryos and their
      interferon-tau (IFNT) secretion amounts during the elongation phase. We assessed
      the induction capability of maternal recognition of pregnancy by parthenogenetic
      embryos and attempted cotransfer of in vivo-fertilized and parthenogenetic
      embryos. The expression level of IFNT mRNA in in vivo-fertilized embryos peaked
      on Day 18 after estrus, and the highest amount of uterine IFNT was observed on
      Day 20. Transfer of 10 parthenogenetic embryos produced a detectable amount of
      uterine IFNT. Transfer of one or three parthenogenetic embryos inhibited
      luteolysis. An increase in ISG15 mRNA levels in peripheral granulocytes was
      induced by the transfer of three parthenogenetic embryos. Cotransfer of three
      parthenogenetic embryos significantly improved the pregnancy rate on Day 40 in
      code 3 in vivo-fertilized embryos compared with single transfer without
      parthenogenetic embryos (65% vs. 35%). However, the pregnancy rate on Day 90
      (35%) in cotransfer of code 3 in vivo-fertilized embryos did not differ from that
      upon single transfer (29%), because the cotransfer group had a higher incidence
      of pregnancy loss than with single transfer (47% vs. 17%) after Day 40.
      Cotransfer did not affect the pregnancy rate of code 2 in vivo-fertilized
      embryos. The incidence of pregnancy loss was higher in cotransfer of code 2 in
      vivo-fertilized embryos than in single transfer (30% vs. 7%). In conclusion,
      parthenogenetic embryos in the elongation phase secreted IFNT, enabling induction
      of maternal recognition of pregnancy. The present study revealed that enhancement
      of the maternal recognition of pregnancy using parthenogenetic embryos promoted
      the viability of poor-quality embryos until Day 40 of gestation. However, the
      incidence of pregnancy loss increased after Day 40 in the cotransfer of
      parthenogenetic embryos. A technique for promoting the full-term survival of poor
      quality embryos is needed.

PMID- 24581588
TI  - A re-evaluation of sperm ultrastructure in the emu, Dromaius novaehollandiae.
AB  - Existing reports on sperm structure in the emu do not adequately illustrate or
      describe all the salient ultrastructural features necessary for a meaningful
      comparison of normal and abnormal sperm in this species. As sperm morphology
      forms an important parameter in determining semen quality, and in view of the
      proposed role of artificial insemination in the farming of ratites, this article
      re-evaluates and complements the existing data on the topic, provides a fully
      illustrated description of emu sperm ultrastructure, and documents some
      unreported morphologic features. Conventional transmission and scanning electron
      microscopy and high resolution scanning electron microscopy were used to describe
      the ultrastructure of sperm harvested from the distal deferent duct of sexually
      mature birds slaughtered during the breeding season. In addition to broadly
      confirming the basic ultrastructural characteristics previously described for emu
      sperm, this study revealed a number of unreported morphologic features. These
      included distinct differences in surface properties between the acrosome and
      nucleus, the presence of a thread-like appendage near the base of the nucleus,
      variable positioning of the annulus relative to structures located at the
      midpiece-principal piece junction and regional differentiation of the principal
      piece. Although the emu displayed similar basic morphologic features to sperm of
      other ratites and the tinamou, marked structural peculiarities were obvious,
      notably the lack of an endonuclear canal and a perforatorium and the presence of
      significantly more mitochondria in the midpiece coupled with an absence of
      intermitochondrial cement. Although the broad morphologic features of emu sperm
      would appear to add credence to the general view that the ratites, together with
      the tinamous, form a monophyletic group at the base of the avian phylogenetic
      tree, it is also clear that emu sperm are distinctly different from those of the
      ostrich, rhea, and tinamou which together share morphologic affinities. This
      observation may lend some support to the alternate view that the Australasian
      ratites represent a separate clade that developed independently from flightless
      ancestors. 

PMID- 24581589
TI  - Long-term and transgenerational effects of cryopreservation on rabbit embryos.
AB  - The short-term effects of cryopreservation and embryo transfer are well
      documented (reduced embryo viability, changes in pattern expression), but little
      is known about their long-term effects. We examined the possibility that embryo
      vitrification and transfer in rabbit could have an impact on the long-term
      reproductive physiology of the offspring and whether these phenotypes could be
      transferred to the progeny. Vitrified rabbit embryos were warmed and transferred
      to recipient females (F0). The offspring of the F0 generation were the F1
      generation (cryopreserved animals). Females from F1 generation offspring were
      bred to F1 males to generate an F2 generation. In addition, two counterpart
      groups of noncryopreserved animals were bred and housed simultaneously to F1 and
      F2 generations (CF1 and CF2, respectively). The reproductive traits studied in
      all studied groups were litter size (LS), number born alive at birth (BA), and
      postnatal survival at Day 28 (number of weaned/number born alive expressed as
      percentage). The reproductive traits were analyzed using Bayesian methodology.
      Features of the estimated marginal posterior distributions of the differences
      between F1 and their counterparts (F1 - CF1) and between F2 and their
      counterparts (F2 - CF2) in reproductive characters found that vitrification and
      transfer procedures cause a consistent increase in LS and BA between F1 and CF1
      females (more than 1.4 kits in LS and more than 1.3 BA) and also between F2 and
      CF2 females (0.96 kits in LS and 0.94 BA). We concluded that embryo
      cryopreservation and transfer procedures have long-term effects on derived female
      reproduction (F1 females) and transgenerational effects on female F1 offspring
      (F2 females). 

PMID- 24581590
TI  - Metastatic melanoma cell lines do not secrete IL-1beta but promote IL-1beta
      production from macrophages.

PMID- 24581591
TI  - Non-cirrhotic portal hypertension--concept, diagnosis and clinical management.
AB  - Non-cirrhotic portal hypertension (NCPH) is mainly related to vascular disorders
      in the portal system, granuloma formation with periportal fibrosis or genetic
      alterations affecting the hepatobiliary system. For the diagnosis of the so
      called idiopathic NCPH, it is essential to rule out chronic liver diseases
      associated with progression to cirrhosis as viral hepatitis B and C, alcoholic
      and non-alcoholic fatty liver, autoimmune disease, hereditary hemochromatosis,
      Wilson's disease as well as primary biliary cirrhosis and primary sclerosing
      cholagitis. This mini review will focus on the most common types of NCPH,
      excluding the idiopathic NCPH. Primary Budd-Chiari syndrome, characterized by
      obstruction of hepatic venous outflow, must be distinguished from sinusoidal
      obstruction syndrome, a cause of portal hypertension associated with exposure to
      toxic plants or therapeutic agents. Noninvasive imaging methods usually help the
      diagnosis of both Budd-Chiari syndrome and portal thrombosis, the later a
      relatively frequent cause NCPH. Clinical presentation and management of these
      vascular disorders are evaluated. Schistosomiasis, a worldwide spread endemic
      parasitic disease, may evolve to severe forms of the disease with huge spleen and
      gastroesophageal varices due to presinusoidal portal hypertension. Although
      management of acute upper gastrointestinal bleeding is similar to that of
      cirrhosis, prevention of rebleeding differs. Instead of portosystemic shunt
      procedures, the esophagogastric devascularization with splenectomy is the
      accepted surgical alternative. Its association with endoscopic therapy is
      suggested to be the best option for PH due to schistosomiasis. In conclusion, the
      prompt diagnosis of the disorder leading to non-cirrhotic portal hypertension is
      essential for its correct management.

PMID- 24581592
TI  - Assessment of tumor blood flow and its correlation with histopathologic features
      in skull base meningiomas and schwannomas by using pseudo-continuous arterial
      spin labeling images.
AB  - OBJECTIVE: We aimed to investigate whether pseudo-continuous arterial spin
      labeling (pcASL)-MRI can adequately evaluate tumor perfusion even if the tumors
      are located in the skull base region and evaluate the correlation between tumor
      blood flow (TBF) and the histopathologic features of skull base meningiomas and
      schwannomas. MATERIALS AND METHODS: We enrolled 31 patients with skull base
      meningioma (n=14) and schwannoma (n=17) who underwent surgical resection. TBF was
      calculated from pcASL. Tissue sections were stained with CD34 to evaluate
      microvessel area (MVA). TBF and MVA ratio were compared between meningiomas and
      schwannomas using Mann-Whitney U-test. The correlations between MVA ratio and TBF
      were evaluated in each tumor by using single linear regression analysis and
      Spearman's rank correlation coefficients (rs). RESULTS: MVA ratio and TBF were
      significantly higher in meningioma than in schwannoma (both p<0.01). Correlation
      analyses revealed significant positive correlations between MVA ratio and both
      mean and max TBF for meningiomas (rs=0.89, 0.81, both p<0.01). There was a weak
      positive correlation between MVA ratio and mean TBF for schwannomas (rs=0.43,
      p=0.04). However, no significant correlation was found between MVA ratio and max
      TBF for schwannoma. CONCLUSIONS: pcASL-MRI is useful for evaluating tumor
      perfusion even if the tumors are located in the skull base region. Moreover,
      pcASL-TBF was significantly higher in most meningiomas compared to schwannomas,
      which can help in the differential diagnosis of the 2 tumor types even without
      the use of contrast material.

PMID- 24581593
TI  - Artefacts induced by coiled intracranial aneurysms on 3.0-Tesla versus 1.5-Tesla
      MR angiography--An in vivo and in vitro study.
AB  - OBJECTIVE: To compare metal-induced artefacts from coiled intracranial aneurysms
      on 3.0-Tesla and 1.5-Tesla magnetic resonance angiography (MRA), since concerns
      persist on artefact enlargement at 3.0Tesla. MATERIALS AND METHODS: We scanned 19
      patients (mean age 53; 16 women) with 20 saccular aneurysms treated with coils
      only, at 1.5 and 3.0Tesla according to standard clinical 3D TOF-MRA protocols
      containing a shorter echo-time but weaker read-out gradient at 3.0Tesla in
      addition to intra-arterial digital subtraction angiography (IA-DSA). Per modality
      two neuro-radiologists assessed the occlusion status, measured residual flow, and
      indicated whether coil artefacts disturbed this assessment on MRA. We assessed
      relative risks for disturbance by coil artefacts, weighted kappa's for agreement
      on occlusion levels, and we compared remnant sizes. For artefact measurements, a
      coil model was created and scanned with the same protocols followed by 2D MR
      scans with variation of echo-time and read-out gradient strength. RESULTS: Coil
      artefacts disturbed assessments less frequently at 3.0Tesla than at 1.5Tesla (RR:
      0.3; 95%CI: 0.1-0.8). On 3.0-Tesla MRA, remnants were larger than on 1.5-Tesla
      MRA (difference: 0.7mm; 95%CI: 0.3-1.1) and larger than on IA-DSA (difference:
      1.0mm; 95%CI: 0.6-1.5) with similar agreement on occlusion levels with IA-DSA for
      both field strengths (kappa 0.53; 95%CI: 0.23-0.84 for 1.5-Tesla MRA and IA-DSA;
      kappa 0.47; 95%CI: 0.19-0.76 for 3.0-Tesla MRA and IA-DSA). Coil model artefacts
      were smaller at 3.0Tesla than at 1.5Tesla. The echo-time influenced artefact size
      more than the read-out gradient. CONCLUSIONS: Artefacts were not larger, but
      smaller at 3.0Tesla because a shorter echo-time at 3.0Tesla negated artefact
      enlargement. Despite smaller artefacts and larger remnants at 3.0Tesla, occlusion
      levels were similar for both field strengths.

PMID- 24581594
TI  - Increasing the accuracy of 18F-FDG PET/CT interpretation of "mildly positive"
      mediastinal nodes in the staging of non-small cell lung cancer.
AB  - INTRODUCTION: The aim of this study was to identify radiological factors that may
      reduce false-positive results and increase diagnostic accuracy when staging the
      mediastinum of patients with non-small cell lung carcinoma (NSCLC). METHODS: This
      was a retrospective, interdisciplinary, per-node analysis study. We included
      patients with NSCLC and mediastinal nodes with an SUV max in the range of 2.5-4.0
      on PET-CT. We hypothesized that the greatest number of false positive cases would
      occur in this cohort of patients. RESULTS: A total of 92 mediastinal lymph nodes
      were analyzed in 44 patients. Mediastinal disease (N2/N3) was histologically
      confirmed in 15 of 44 patients and in 34 of 92 lymph nodes; positive predictive
      value of 37% and false positive rate of 63%. Lymph node SUV max, tumor size,
      ratio of node SUV max to tumor SUV max (SUVn/SUVp), and ratio of node SUV max to
      node size (SUV n/SADn) were significantly higher in true positive cases. Using a
      threshold of 0.3 for SUV node/tumor and 3 for SUV node/size yielded sensitivities
      of 91% and 71% and specificities of 71% and 69% respectively for the detection of
      mediastinal disease. Using both ratios in combination resulted in a sensitivity
      of 65% and a specificity of 88%. Concurrent benign lung disease was observed
      significantly more frequently in false-positive cases. CONCLUSION: SUVn/SUVpt and
      SUVn/SADn may be complimentary to conventional visual interpretation and SUV max
      measurement in the assessment of mediastinal disease in patients with NSCLC.

PMID- 24581595
TI  - Diffusion-weighted imaging in assessing renal pathology of chronic kidney
      disease: A preliminary clinical study.
AB  - OBJECTIVE: To investigate the clinical potential of diffusion-weighted imaging
      (DWI) in assessing renal pathology of chronic kidney disease (CKD). METHODS:
      Seventy-one CKD patients and twelve healthy volunteers were examined using DWI
      with prospective acquisition correction. Renal biopsy specimens from the CKD
      patients were scored based on the severity of renal pathology and to confirm
      pathology type. CKD patients were divided into three groups according to
      pathology scores: mild, moderate, or severe. The association between renal
      apparent diffusion coefficient (ADC) values and pathology scores was investigated
      using Pearson's correlation and single factor analysis of variance. Multiple
      linear regression analysis was performed to explore associations between renal
      ADC values and pathology score, glomerular filtration rate, serum creatinine, and
      age. The Kruskal-Wallis H test was conducted to compare ADC values and pathology
      type. RESULTS: Renal ADC values correlated negatively with pathology scores (r=
      0.633, P<0.001). The ADC values among the four groups (mild, moderate, severe
      impairment, and controls) were significantly different (F=19.512, P<0.001).
      However, when patients were stratified by pathology type, no significant
      differences were found in ADC values among these groups (chi(2)=9.929, P=0.270).
      Further multiple linear regression analysis showed that only the pathology score
      and ADC values were related (t=-4.586, P=0.000). CONCLUSIONS: DWI has clinical
      potential in assessing the severity of renal pathology in CKD and shows promise
      as a non-invasive and effective technique to guide therapy and follow-up.

PMID- 24581596
TI  - Hepatic steatosis is associated with increased hepatic FDG uptake.
AB  - OBJECTIVE: The use of liver as a reference tissue for semi-quantification of
      tumour FDG uptake may not be valid in hepatic steatosis (HS). Previous studies on
      the relation between liver FDG uptake and HS have been contradictory probably
      because they ignored blood glucose (BG). Because hepatocyte and blood FDG
      concentrations equalize, liver FDG uptake parallels BG, which must therefore be
      considered when studying hepatic FDG uptake. We therefore re-examined the
      relation between HS and liver uptake taking BG into account. METHODS: This was a
      retrospective study of 304 patients undergoing routine PET/CT with imaging 60min
      post-FDG. Average standard uptake value (SUVave), maximum SUV (SUVmax) and CT
      density (index of HS) were measured in a liver ROI. Blood pool SUV was based on
      the left ventricular cavity (SUVLV). Correlations were assessed using least
      squares fitting of continuous data. Patients were also divided into BG subgroups
      (<4, 4-5, 5-6, 6-8, 8-10 and 10+mmol/l). RESULTS: SUVave, SUVmax and SUVLV
      displayed similar relations with BG. SUVmax/SUVLV, but not SUVave/SUVLV,
      correlated significantly with BG. SUVmax, but not SUVave, correlated inversely
      with CT density before and after adjusting for BG. SUVmax/SUVave correlated more
      strongly with CT density than SUVmax. CT density correlated inversely with
      SUVmax/SUVLV but positively with SUVave/SUVLV. CONCLUSIONS: Hepatic SUV is more
      influenced by BG than by HS. Its relation with BG renders it unsuitable as a
      reference tissue. Nevertheless, hepatic fat does correlate positively with liver
      SUV, although this is seen only with SUVmax because SUVave is 'diluted' by
      hepatic fat.

PMID- 24581597
TI  - Multiple transmissible genes encoding fluoroquinolone and third-generation
      cephalosporin resistance co-located in non-typhoidal Salmonella isolated from
      food-producing animals in China.
AB  - The aim of this study was to identify genes conferring resistance to
      fluoroquinolones and extended-spectrum beta-lactams in non-typhoidal Salmonella
      (NTS) from food-producing animals in China. In total, 31 non-duplicate NTS were
      obtained from food-producing animals that were sick. Isolates were identified and
      serotyped and the genetic relatedness of the isolates was determined by pulsed
      field gel electrophoresis of XbaI-digested chromosomal DNA. Antimicrobial
      susceptibility was determined using Clinical and Laboratory Standards Institute
      methodology. The presence of extended-spectrum beta-lactamase (ESBL) and
      fluoroquinolone resistance genes was established by PCR and sequencing. Genes
      encoded on transmissible elements were identified by conjugation and
      transformation. Plasmids were typed by PCR-based replicon typing. The occurrence
      and diversity of numerous different transmissible genes conferring
      fluoroquinolone resistance [qnrA, qnrD, oqxA and aac(6')-Ib-cr] and ESBLs (CTX-M
      27 and CTX-M-14), and which co-resided in different isolates and serovars of
      Salmonella, were much higher than in European countries. Furthermore, different
      plasmids encoded fluoroquinolone resistance (ca. 6 kb) and beta-lactam resistance
      (ca. 63 kb) and these co-resided in isolates with mutations in topoisomerase
      genes (gyrA and parC) giving very resistant Salmonella. The presence of multidrug
      resistant bacteria in food-producing animals in countries that export foodstuffs
      suggests that global transfer of antibiotic resistances from country to country
      on food is possible.

PMID- 24581598
TI  - Reprint of "Syphilitic aortic aneurysm missed on the chest radiography".

PMID- 24581599
TI  - Extended use of alanine irradiated in experimental reactor for combined gamma-
      and neutron-dose assessment by ESR spectroscopy and thermal neutron fluence
      assessment by measurement of (14)C by LSC.
AB  - Gamma- and neutron doses in an experimental reactor were measured using
      alanine/electron spin resonance (ESR) spectrometry. The absorbed dose in alanine
      was decomposed into contributions caused by gamma and neutron radiation using
      neutron kerma factors. To overcome a low sensitivity of the alanine/ESR response
      to thermal neutrons, a novel method has been proposed for the assessment of a
      thermal neutron flux using the (14)N(n,p) (14)C reaction on nitrogen present in
      alanine and subsequent measurement of (14)C by liquid scintillation counting
      (LSC). 

PMID- 24581600
TI  - Characterization measurement of a thick CdTe detector for BNCT-SPECT - detection
      efficiency and energy resolution.
AB  - Author's group is carrying out development of BNCT-SPECT with CdTe device, which
      monitors the therapy effect of BNCT in real-time. From the design calculations,
      the dimensions were fixed to 1.5*2*30mm(3). For the collimator it was confirmed
      that it would have a good spatial resolution and simultaneously the number of
      counts would be acceptably large. After producing the CdTe crystal, the
      characterization measurement was carried out. For the detection efficiency an
      excellent agreement between calculation and measurement was obtained. Also, the
      detector has a very good energy resolution so that gamma-rays of 478keV and
      511keV could be distinguished in the spectrum. 

PMID- 24581601
TI  - WNT9B in 542 Chinese women with Mullerian duct abnormalities: mutation analysis.
AB  - The WNT9B gene is a common organizing signal regulating different segments of the
      mammalian urogenital system and plays a primary role in the development of the
      female reproductive tract. The aim of the present work was to examine the
      presence of WNT mutations in a population of women with Mullerian duct
      abnormalities (MDA) in order to elucidate whether mutations in WNT9B are
      causative for MDA in Chinese women. Initially, 191 Chinese MDA patients and 192
      healthy individuals (controls) were recruited. All coding regions were amplified
      by PCR and sequenced to search for variants. To verify the initial results, the
      numbers of patients and ethnic-matched controls were expanded to 542 and 563,
      respectively. One known single-nucleotide polymorphism and four novel variants
      were identified in the first stage: two were synonymous; the other two were rare
      nonsynonymous novel variants (c.566G>A (p.Arg189Gln) and c.773G>A (p.Arg258His)).
      None of the four novel variants was found in controls. In the second stage, both
      novel nonsynonymous variants were detected in MDA cases and controls. The results
      indicate that mutations in the coding sequence of WNT9B are not responsible for
      MDA in the Chinese population.

PMID- 24581602
TI  - Correlation between aneuploidy, apoptotic markers and DNA fragmentation in
      spermatozoa from normozoospermic patients.
AB  - Genetic and biochemical sperm integrity is essential to ensure the reproductive
      competence. However, spermatogenesis involves physiological changes that could
      endanger sperm integrity. DNA protamination and apoptosis have been studied
      extensively. Furthermore, elevated rates of aneuploidy and DNA injury correlate
      with reproductive failures. Consequently, this study applied the conventional
      spermiogram method in combination with molecular tests to assess genetic
      integrity in ejaculate from normozoospermic patients with implantation failure by
      retrospectively analysing aneuploidy (chromosomes 18, X, Y), DNA fragmentation,
      externalization of phosphatidylserine and mitochondrial membrane potential status
      before and after magnetic activated cell sorting (MACS). Aneuploid, apoptotic and
      DNA-injured spermatozoa decreased significantly after MACS. A positive
      correlation was detected between reduction of aneuploidy and decreased DNA
      damage, but no correlation was determined with apoptotic markers. The
      interactions between apoptotic markers, DNA integrity and aneuploidy, and the
      effect of MACS on these parameters, remain unknown. In conclusion, use of MACS
      reduced aneuploidy, DNA fragmentation and apoptosis. A postulated mechanism
      relating aneuploidy and DNA injury is discussed; on the contrary, cell death
      markers could not be related. An 'apoptotic-like' route could explain this
      situation.

PMID- 24581622
TI  - [Tourniquet use in civil and military medicines].
AB  - OBJECTIVES: The purpose of this literature review is, after a history and a point
      about current situation, to present the military use and precautions of use of
      tourniquet for civil and military medicine. DATA SOURCES: A review of the Anglo
      Saxon and French literature was performed in PUBMED database, from 1962 to 2012.
      The research was conducted using the following keywords: "tourniquet",
      "complications", "haemorrhage", "emergency", "military medicine", used alone or
      in combination. DATA EXTRACTION: The extracted data concerned the history, the
      epidemiology, the interest of tourniquet during peacetime and wartime, adverse
      effects and the ratio benefit/risk. DATA SYNTHESIS: The tourniquet is "a device
      which is tightened, in case of haemorrhage, around a limb in order to slow or
      stop the venous or arterial circulation before surgery...". This item is thus
      used in surgery to reduce intraoperative bleeding and in emergency medicine as a
      rescue technique for bleeding places non accessible to compression or to other
      technical hemostasis. It is also used for treating bleeding of mass casualties.
      However, its use is too poorly managed by health professionals and it remains
      risky. Recent armed conflicts have yet revived its day use. CONCLUSION: The
      tourniquet has utility in times of war and in peacetime. In each case,
      indications and complications must be known.

PMID- 24581623
TI  - Shaping academic medicine.

PMID- 24581624
TI  - Biomedicine: a word of two halves.

PMID- 24581626
TI  - The goals of National Institute for Health Research funding for trainees.

PMID- 24581625
TI  - Stratified medicines: towards better treatment for disease.

PMID- 24581627
TI  - Engaging with the media.

PMID- 24581628
TI  - Engaging with health-care policy.

PMID- 24581629
TI  - Biosurfactant stabilized anticancer biomolecule-loaded poly (D,L-lactide)
      nanoparticles.
AB  - PLA nanoparticles (NPs) were prepared via green route using turmeric (Curcuma
      longa) extract (TE) as biostabiliser/biosurfactant. Of the 29 formulations, two
      formulations of TE synthesized PLA NPs were evaluated for encapsulation and
      controlled release of well known antioxidant and less bioavailable molecules
      curcumin and quercetin. Size of curcumin loaded PLA NPs synthesized using 0.8
      mg/ml PLA (C-En-D) and 0.1 mg/ml PLA (C-En-P) were 203+/-77 and 110+/-44 nm,
      respectively. However, quercetin loaded PLA NPs synthesized at 0.8 mg/ml (Q-En-D)
      and 0.1mg/ml (Q-En-P) PLA concentrations were 170+/-95 and 102+/-31 nm,
      respectively. The encapsulation efficiency of curcumin loaded PLA (C-En-D and C
      En-P) NPs as well as quercetin loaded PLA (Q-En-D and Q-En-P) NPs was found ~95%.
      In vitro release study of C-En-D, C-En-P, Q-En-D and Q-En-P NPs showed initial
      burst release followed by slow and sustained release. C-En-D NPs and Q-En-D NPs
      showing maximum in vitro release (~100%) were evaluated for cytotoxicity. Blank
      PLA NPs, C-En-D and Q-En-D NPs were found to be safe against normal human
      leukocytes up to 2 mg/ml dose. Both C-En-D and Q-En-D NPs showed anticancer
      activity against A549 cell line. But Q-En-D NPs showed better anticancer activity
      than C-En-D NPS on A549 cells. While blank PLA NPs did not possess anticancer
      activity. TE extract stabilized PLA NPs were non-toxic, biocompatible and safe to
      normal human leukocytes. Such technology will be better, effective and safer in
      use for anticancer as well as other biological application.

PMID- 24581630
TI  - The psychological flexibility model: a basis for integration and progress in
      psychological approaches to chronic pain management.
AB  - Scientific models are like tools, and like any tool they can be evaluated
      according to how well they achieve the chosen goals of the task at hand. In the
      science of treatment development for chronic pain, we might say that a good model
      ought to achieve at least 3 goals: 1) integrate current knowledge, 2) organize
      research and treatment development activities, and 3) create progress. In the
      current review, we examine models underlying current cognitive behavioral
      approaches to chronic pain with respect to these criteria. A relatively new model
      is also presented as an option, and some of its features examined. This model is
      called the psychological flexibility model. This model fully integrates cognitive
      and behavioral principles and includes a process-oriented approach of treatment
      development. So far it appears capable of generating treatment applications that
      range widely with regard to conditions targeted and modes of delivery and that
      are increasingly supported by evidence. It has led to the generation of
      innovative experiential, relationship-based, and intensive treatment methods. The
      scientific strategy associated with this model seeks to find limitations in
      current models and to update them. It is assumed within this strategy that all
      current treatment approaches will one day appear lacking and will change.
      PERSPECTIVE: This Focus Article addresses the place of theory and models in
      psychological research and treatment development in chronic pain. It is argued
      that such models are not merely an academic issue but are highly practical. One
      potential model, the psychological flexibility model, is examined in further
      detail.

PMID- 24581631
TI  - Psychological flexibility: what theory and which predictions?

PMID- 24581632
TI  - Using theoretical models to clarify shared and unique mechanisms in psychosocial
      pain treatments: a commentary on McCracken and Morley's theoretical paper.

PMID- 24581633
TI  - Reply to Johan W. S. Vlaeyen and to Melissa A. Day and Beverly E. Thorn.

PMID- 24581635
TI  - Perceptions and satisfaction of aesthetic outcome following secondary cleft
      rhinoplasty: evaluation by patients versus health professionals.
AB  - OBJECTIVE: To explore how improvement in facial appearance is related to
      patients' perception and satisfaction following cleft rhinoplasty. DESIGN: A
      cross-sectional survey. PARTICIPANTS: 35 cleft rhinoplasty patients treated
      between 2005 and 2010. 45 observers comprised of healthcare professionals. MAIN
      OUTCOME MEASURES: Evaluation of patient satisfaction including Rhinoplasty
      Outcome Evaluation (ROE) questionnaire, Preoperative and Postoperative Semi
      quantitative Ordinal Scale Rating (PPSOSR) and a specifically designed semi
      structured questionnaire. Evaluation by panel of observers using Asher-McDade
      Aesthetic Index (AMAI) Rating and PPSOSR. RESULTS: Patient satisfaction was high,
      based on the ROE questionnaire (score 76.1). 91% of patients rated their
      appearance as improved, 3% remained 'uncertain' and 6% felt 'different but not
      improved.' Teenage females (score 94.1) showed statistically higher satisfaction,
      when compared to older females (score 75.5), or their male counterparts (score
      69.8). The preoperative appearance ratings were not statistically different
      between patients and panel members but postoperatively, patients' rating of their
      appearance was statistically higher. All components of the AMAI were scored
      between 'good' to 'fair' (score 9.3). Seventy percent of the panel rated the
      postoperative appearance as improved. Interestingly, 10% rated the postoperative
      appearance as 'unchanged', while 3% reported a 'worsened' appearance. There was
      no correlation between panel assessment of aesthetic outcome and patient
      satisfaction. CONCLUSIONS: Cleft rhinoplasty contributes to subjective patient
      satisfaction as a result of their perceived improvement in appearance and
      function, even though this was not correlated to objective aesthetic rating by
      panel members.

PMID- 24581636
TI  - Submental artery island flap in intraoral reconstruction: a review.
AB  - BACKGROUND: The submental flap was first introduced 20 years ago (1993). Advances
      in techniques and new findings from anatomic studies expanded the indications and
      improved the flap characteristics. Indications, limitation, and all possible
      variants of this flap are discussed comprehensively in this article. MATERIALS
      AND METHODS: A literature review was performed. We paid attention to the anatomy
      of submental region, and especially to submental artery and vein, muscles and
      lymphatics. Surgical techniques for each possible variant of this flap and
      examples of each situation are presented. Indications of submental flap for
      facial, oesophageal, pharyngeal, laryngeal, and oral cavity reconstruction were
      assessed. RESULTS: Ninety studies meeting the inclusion criteria were reviewed.
      Classification of the submental flap based on skin paddle composition and blood
      supply is presented. Major modifications such as pedicled, free, and perforator
      flaps are discussed comprehensively and minor variants of submental flap such as
      bipaddled, bipedicled, expanded, deepithelialized, and interposition submental
      flaps are discussed, briefly. A historical look at this topic is presented to
      show how and by whom advances in submental flap were done. CONCLUSION: The
      submental flap has a wide arc of rotation; it is easy to rise and has low donor
      site morbidity. It is a safe, simple, and predictable method for reconstruction
      of oral cavity.

PMID- 24581634
TI  - The ACTTION-American Pain Society Pain Taxonomy (AAPT): an evidence-based and
      multidimensional approach to classifying chronic pain conditions.
AB  - Current approaches to classification of chronic pain conditions suffer from the
      absence of a systematically implemented and evidence-based taxonomy. Moreover,
      existing diagnostic approaches typically fail to incorporate available knowledge
      regarding the biopsychosocial mechanisms contributing to pain conditions. To
      address these gaps, the Analgesic, Anesthetic, and Addiction Clinical Trial
      Translations Innovations Opportunities and Networks (ACTTION) public-private
      partnership with the U.S. Food and Drug Administration and the American Pain
      Society (APS) have joined together to develop an evidence-based chronic pain
      classification system called the ACTTION-APS Pain Taxonomy. This paper describes
      the outcome of an ACTTION-APS consensus meeting, at which experts agreed on a
      structure for this new taxonomy of chronic pain conditions. Several major issues
      around which discussion revolved are presented and summarized, and the structure
      of the taxonomy is presented. ACTTION-APS Pain Taxonomy will include the
      following dimensions: 1) core diagnostic criteria; 2) common features; 3) common
      medical comorbidities; 4) neurobiological, psychosocial, and functional
      consequences; and 5) putative neurobiological and psychosocial mechanisms, risk
      factors, and protective factors. In coming months, expert working groups will
      apply this taxonomy to clusters of chronic pain conditions, thereby developing a
      set of diagnostic criteria that have been consistently and systematically
      implemented across nearly all common chronic pain conditions. It is anticipated
      that the availability of this evidence-based and mechanistic approach to pain
      classification will be of substantial benefit to chronic pain research and
      treatment. PERSPECTIVE: The ACTTION-APS Pain Taxonomy is an evidence-based
      chronic pain classification system designed to classify chronic pain along the
      following dimensions: 1) core diagnostic criteria; 2) common features; 3) common
      medical comorbidities; 4) neurobiological, psychosocial, and functional
      consequences; and 5) putative neurobiological and psychosocial mechanisms, risk
      factors, and protective factors.

PMID- 24581637
TI  - A year in review.

PMID- 24581638
TI  - AORN's support of ambulatory perioperative nursing.

PMID- 24581639
TI  - Another perspective on forced-air warming and the risk of surgical site
      infection.

PMID- 24581640
TI  - Author response.

PMID- 24581641
TI  - Reconsidering recommendations for blanket warming.

PMID- 24581642
TI  - Author response.

PMID- 24581643
TI  - Using preoperative assessment and patient instruction to improve patient safety.
AB  - Rates of patient transfers, cancellations, and patient visits to the emergency
      department after discharge are quality metrics for ambulatory surgery centers. To
      improve these metrics, it is imperative to establish best practices for
      conducting preoperative assessments, including identifying key patient conditions
      (ie, obstructive sleep apnea, cardiovascular disease, reactive airway disease,
      obesity). To guide appropriate patient selection, practitioners should review the
      patient's allergies and sensitivities, alcohol use, medications, and medical
      history. To help ensure good patient outcomes, it is imperative to provide
      complete preoperative instructions (eg, NPO guidelines, medications, what to
      bring, cancellation instructions) and discharge instructions (eg, postoperative
      medications, appropriate activity restrictions, diet, surgical and anesthetic
      side effects, special circumstances [eg, regional blocks], symptoms of possible
      complications, treatment and tests, access to postdischarge follow-up care).
      Generally, the routine outpatient surgical patient is discharged home; however,
      there are circumstances that occasionally necessitate transfer or admission to a
      higher level of care. For transfers, ambulatory surgery centers should adhere to
      applicable federal and state guidelines and should have a clear policy in place
      to guide transfers.

PMID- 24581644
TI  - A look at best practices for patient education in outpatient spine surgery.
AB  - Following best practices for patient education helps ensure patients and their
      family members leave an ambulatory surgery center after a procedure with a
      functional understanding of all aspects of surgery, ongoing care, and
      postoperative expectations. Best practices for education of patients undergoing
      spine surgery in an ambulatory surgery center include a consistent and informed
      staff, involved patients and family members, patient-specific education, and
      continual reinforcement of that education. Patient education needs to include
      topics such as expectations, the recovery process, and pain control.

PMID- 24581645
TI  - Cardiac emergency simulation: drilling for success in the ambulatory setting.
AB  - The "see one, do one, teach one" method of clinical teaching is no longer
      practical for preparing perioperative personnel to respond to emergency
      situations. Teaching with simulation trains team members to respond to unexpected
      events and enables them to provide care when an emergency situation arises.
      Simulation drills resemble clinical practice and allow personnel to apply and
      integrate skills, teamwork, and critical thinking. This article provides
      information and tools for performing cardiac simulation drills in the ambulatory
      setting. Tools included are a 10-step guide to simulation drills, a scenario,
      roles and duties to assign during a drill, and a drill evaluation form.

PMID- 24581646
TI  - Ensuring patient safety and optimizing efficiency during gastrointestinal
      endoscopy.
AB  - The volume of outpatient gastrointestinal (GI) endoscopy has grown dramatically
      in the past three decades, fueled by advancing technologies and evolving payment
      policies. This magnifies the need to ensure high-quality, safe, and cost
      effective endoscopic services. In recent years, publicized breaches in standards
      of care for GI endoscopy have intensified the focus on patient safety. Because of
      these patient safety concerns and changes in regulatory policies, some ambulatory
      surgery center surveyors and inspectors have held GI endoscopy suites to the same
      standards as hospital ORs. The American Society for Gastrointestinal Endoscopy
      and other endorsing organizations drafted the Guidelines for Safety in the
      Gastrointestinal Endoscopy Unit, which published in January 2014. These safety
      guidelines relevant to sedation, infection control, staffing, training, technical
      equipment, traffic patterns, and personal protective equipment differ from other
      published guidelines for the outpatient surgical setting.

PMID- 24581647
TI  - Back to basics: speak up.
AB  - Being able to identify problems and bring them to the attention of OR team
      colleagues is crucial for the safety of both patients and perioperative team
      members; however, being able to do this means being comfortable with speaking up
      under circumstances that may be difficult. Disruptive or intimidating coworker
      behavior also makes speaking up difficult, but it is important to address in the
      interest of providing safe, effective care to patients. To remedy this, health
      care workers should create awareness of the problem and motivate others to take
      action; establish a culture of respect; set expectations to help eliminate
      disrespectful behavior; and create a learning environment that eliminates
      hierarchical structures, fosters professionalism, demonstrates respect, and
      enforces a zero tolerance policy.

PMID- 24581648
TI  - Developing a moderate sedation policy: essential elements and evidence-based
      considerations.
AB  - Developing an institutional policy for moderate sedation is a multidisciplinary
      effort that should involve close collaboration among clinicians, administrators,
      and risk managers. A variety of health care providers administer moderate
      sedation. Sedation policy should address essential elements, such as clinician
      training and credentialing, equipment, preprocedure evaluation, periprocedure
      patient monitoring, postprocedure observation and discharge, pharmaceutical
      agents, and outcomes assessment. Sedation policy should comply with local, state,
      and national guidelines and standards. Furthermore, sedation policy should be
      evidence based to incorporate the latest information about best practices and
      outcomes. Advances in pharmacology, monitoring, medication delivery systems, and
      simulation training can help improve quality of care and patient safety in the
      administration of moderate sedation.

PMID- 24581649
TI  - A successful life safety survey in an ambulatory surgery center.

PMID- 24581651
TI  - Empty handoff.

PMID- 24581652
TI  - Every newborn, every mother, every adolescent girl.

PMID- 24581653
TI  - North Korea: evidence of intolerable human rights violations.

PMID- 24581654
TI  - The cost of health care in Australia.

PMID- 24581655
TI  - The health implications of fracking.

PMID- 24581656
TI  - The Lancet Psychiatry: a call for papers.

PMID- 24581658
TI  - James Watson: thinking outside the genome.

PMID- 24581659
TI  - Debates in medicine: global representation in medical discourse.

PMID- 24581660
TI  - Secukinumab for ankylosing spondylitis.

PMID- 24581661
TI  - Secukinumab for ankylosing spondylitis.

PMID- 24581662
TI  - Secukinumab for ankylosing spondylitis--authors' reply.

PMID- 24581663
TI  - Cardiomyopathy in children: importance of aetiology in prognosis.

PMID- 24581664
TI  - Cardiomyopathy in children: importance of aetiology in prognosis--authors' reply.

PMID- 24581666
TI  - Criminalising homosexuality threatens the fight against HIV/AIDS.

PMID- 24581665
TI  - Laicite in medical schools: a French paradox?

PMID- 24581667
TI  - Independent drug information in Burkina Faso is key to improving public health.

PMID- 24581668
TI  - Type 2 diabetes as a redox disease.

PMID- 24581669
TI  - Flank pain caused by slipping rib syndrome.

PMID- 24581670
TI  - Acute vertigo due to hemispheric stroke: a case report and comprehensive review
      of the literature.
AB  - Acute cortical lesions rarely cause vertigo. We report a 51-year-old patient
      presenting with an acute vestibular syndrome including spontaneous vertigo and
      nystagmus, lateropulsion and nausea due to middle cerebral artery infarction. The
      central origin of the acute vestibular syndrome was revealed by a normal head
      impulse test. A comprehensive literature review on patients with hemispheric
      stroke manifesting with acute vertigo is provided. Typically, patients with an
      acute vestibular syndrome due to cortical stroke have involvement of the
      temporoparietal junction.

PMID- 24581671
TI  - Long-term prognosis for hearing recovery in stroke patients presenting vertigo
      and acute hearing loss.
AB  - BACKGROUND AND PURPOSE: Vertebrobasilar ischemic stroke (VBIS) can cause acute
      hearing loss (AHL) because the vertebrobasilar system supplies most of the
      auditory system including the inner ear. The aim of this study was to assess the
      long-term prognosis of AHL associated with VBIS. METHODS: Over 12.5 years, 62
      patients with AHL of a vascular cause who were followed for at least 1 year
      (mean, 49.2 months; SD, 24.4 months) were enrolled in this study. Quantitative
      audiovestibular function testing was performed during the acute (mostly within 10
      days after symptom onset) and last follow-up periods in all patients. RESULTS: On
      the last follow-up, approximately 65% (39/62) of the patients showed a partial
      (n=24) or complete (n=15) hearing recovery. All but 2 (97%) patients had acute
      vertigo and 56 (56/62, 90%) had a unilateral canal paresis to caloric stimulation
      on the side of the AHL. The most commonly infarcted territory on brain MRI was in
      the distribution of the anterior inferior cerebellar artery (55/62, 89%).
      Multivariable analysis showed that multiple risk factors for stroke [odds ratio
      (OR) 10.46, 95% confidence interval (CI) 1.72 to 13.7, p=0.011] and profound
      hearing loss [OR 3.92, 95% CI 1.03 to 14.97, p<0.046] predicted a poor outcome
      for recovery of hearing loss. CONCLUSIONS: Acute hearing loss associated with
      posterior circulation ischemic stroke exhibits a relatively good long-term
      outcome. Two or more risk factors for stroke and profound hearing loss are
      adverse prognostic factors for recovery of hearing loss of a vascular cause.

PMID- 24581673
TI  - Prolyl hydroxylase domain-2 (PHD2) inhibition may be a better therapeutic
      strategy in renal anemia.
AB  - Recombinant human erythropoietin (rHuEPO) has revolutionized the life of dialysis
      patients with anemia of chronic kidney disease (CKD). Newer erythropoietin
      analogues with improved profile have been introduced recently. However, there are
      many concerns such as safety, economy and patient compliance with these newer
      rHuEPo analogues. Small molecules aimed to inhibit prolyl hydroxylase domain-2
      (PHD2) may prevent degradation of hypoxia inducible factor-2 (HIF2) which leads
      to endogenous erythropoietin production. This therapeutic intervention may not
      only overcome the patient compliance and economic burden but also possibly
      overcome the safety issues related to rHuEPO and its analogues. Moreover, PHD2
      inhibitors may increase the endogenous circulating iron availability via
      suppression of hepcidin, a master regulator of iron homeostasis which further
      reduces the need for exogenous intravenous iron administration for effective
      erythropoiesis in renal anemia patients. In conclusion, small molecule PHD2
      inhibitors may have better therapeutic efficacy and potential to address clinical
      concerns associated with rHuEPO and rHuEPO mimetic peptides. 

PMID- 24581674
TI  - Prevention of cerebral palsy, autism spectrum disorder, and attention deficit
      hyperactivity disorder.
AB  - This hypothesis states that cerebral palsy (CP), autism spectrum disorder (ASD),
      and attention-deficit/hyperactivity disorder (ADHD) are all caused by an
      exaggerated central nervous system inflammatory response to a prenatal insult.
      This prenatal insult may be one or more episodes of ischemia-reperfusion, an
      infectious disease of the mother or the fetus, or other causes of maternal
      inflammation such as allergy or autoimmune disease. The resultant fetal
      inflammatory hyper-response injures susceptible neurons in the developing white
      matter of the brain in specific areas at specific gestational ages. The
      exaggerated neuroinflammatory response is theorized to occur between about 19 and
      34 post-conception weeks for CP, about 32 and 40 weeks for ADHD, and about 36 and
      48 weeks (i.e. 2 months after delivery) for ASD. The exaggerated inflammatory
      response is hypothesized to occur because present diets limit intake of effective
      antioxidants and omega-3 polyunsaturated fatty acids while increasing intake of
      omega-6 polyunsaturated fatty acids. Oxidation products of the omega-3 fatty
      acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) limit
      neuroinflammation while oxidation products of the omega-6 fatty acid arachidonic
      acid exacerbate inflammation. Preventative treatment should begin in all pregnant
      women during the first trimester and should include both DHA and an effective
      antioxidant for prevention of neuroinflammation. The suggested antioxidant would
      be N-acetylcysteine, though melatonin could be chosen instead. Combined DHA and
      NAC therapy is theorized to decrease the incidence of the three disorders by more
      than 75%.

PMID- 24581672
TI  - Decreased physical activity predicts cognitive dysfunction and reduced cerebral
      blood flow in heart failure.
AB  - OBJECTIVE: Cognitive impairment in heart failure (HF) is believed to result from
      brain hypoperfusion subsequent to cardiac dysfunction. Physical inactivity is
      prevalent in HF and correlated with reduced cardiac and cognitive function. Yet,
      no longitudinal studies have examined the neurocognitive effects of physical
      inactivity in HF. The current study examined whether reduced physical activity
      increases risk for cognitive impairment and brain hypoperfusion over time in HF.
      METHODS: At baseline and 12 months later, 65 HF patients underwent
      neuropsychological testing, transcranial Doppler ultrasonography, and were asked
      to wear an accelerometer for seven days. RESULTS: Lower baseline step count and
      less time spent in moderate free-living activity best predicted worse
      attention/executive function and decreased cerebral perfusion at the 12-month
      follow-up. Decreased baseline cerebral perfusion also emerged as a strong
      predictor of poorer 12-month attention/executive function. CONCLUSIONS: Lower
      physical activity predicted worse cognition and cerebral perfusion 12 months
      later in HF. Physical inactivity in HF may contribute to cognitive impairment and
      exacerbate risk for conditions such as Alzheimer's disease. Larger studies are
      needed to elucidate the mechanisms by which physical inactivity leads to
      cognitive dysfunction in HF, including clarification of the role of cerebral
      hypoperfusion.

PMID- 24581675
TI  - Alterations in brain temperatures as a possible cause of migraine headache.
AB  - Migraine is a debilitating disease with a recurring generally unilateral headache
      and concomitant symptoms of nausea, vomiting and photo- and/or phonophobia that
      affects some 11-18% of the population. Most of the mechanisms previously put
      forward to explain the attacks have been questioned or give an explanation only
      some of the symptoms. Moreover, the best drugs for treatment are still the 20
      year-old triptans, which have serious limitations as regards both efficacy and
      tolerability. As the dura and some cranial vessels are the only intracranial
      structures capable of pain sensations, a vascular theory of migraine emerged, but
      has been debated. Recent theories identified the hyperexcitability of structures
      involved in pain transmission, such as the trigeminal system or the cortex, or an
      abnormal modulatory function of the brainstem. However, there is ongoing
      scientific debate concerning these theories, neither of which is fully capable of
      explaining the occurrence of a migraine attack. The present article puts forward
      a hypothesis of the possibility of abnormal temperature regulation in certain
      regions or the overall brain in migraineurs, the attack being a defense mechanism
      to prevent neuronal damage. Few examinations have been made of temperature
      regulation in the human brain. It lacks the carotid rete, a vascular heat
      exchanger that serves in many animals to provide constant brain temperature. The
      human brain contains a high density of neurons with a considerable energy demand
      that is converted to heat. The human brain has a higher temperature than other
      parts of the body and needs continuous cooling. Recent studies revealed
      unexpectedly great variations in temperature of various structures of the brain
      and considerable changes in response to functional activation. There is various
      evidence in support of the hypothesis that accumulated heat in some structure or
      the overall brain may be behind the symptoms observed, such as a platelet
      abnormality, a decreased serotonin content, and dural "inflammation" including
      vasodilation and brainstem activation. The hypothesis postulates that a migraine
      attack serves to restore the brain temperature. Abnormally low temperatures in
      the brain can also result in headache. Surprisingly, no systematic examination of
      brain temperature changes in migraineurs has been published. Certain case reports
      support the present hypothesis. Various noninvasive technologies (e.g. MR)
      capable of monitoring brain temperature are available. If a systematic
      examination of local brain temperature revealed abnormalities in structures
      presumed to be involved in migraine, that would increase our understanding of the
      disease and trigger the development of improved treatment. 

PMID- 24581676
TI  - Low dietary sodium in diabetes nephropathy.
AB  - In a meta-analysis that investigated the effects of dietary sodium restriction in
      diabetes nephropathy, although blood pressure fell, there were significant
      increases in plasma renin and aldosterone levels. In this article, we hypothesise
      that in diabetic nephropathy, ACE-I or ARB treatment attenuates any rise in RAS
      hormones that might result from dietary salt restriction and that the beneficial
      effects of the salt restriction such as a lower blood pressure outweigh any
      potentially negative consequences of RAS activation such as a rise in
      intraglomerular pressure because of the synergistic effects of sodium restriction
      and RAS antagonist therapy. 

PMID- 24581677
TI  - Use of the Lumitex MD Lightmat(r) Surgical Illuminator for pediatric genital
      trauma cases: a retrospective case series.
AB  - STUDY OBJECTIVES: To review the literature regarding repair of pediatric female
      genital trauma. To review our experience with the use of a lighted retractor at
      the time of repair of genital trauma in an operating room setting. STUDY DESIGN:
      Retrospective case series. SETTING: Texas Children's Hospital. PARTICIPANTS:
      Patients with genital trauma requiring repair in an operating room setting where
      the Lumitex MD Lightmat Surgical Illuminator (LM) was utilized. INTERVENTIONS:
      Use of the LM in pediatric gynecology patients. RESULTS: Of the 16 cases where
      the LM lighted retractor was utilized, 12 were found to be performed secondary to
      genital trauma, resulting from straddle injury or coital trauma. Four patients
      were identified as having either congenital reproductive tract anomalies or
      foreign body. Patients ranged in age from 1-21 years with a mean age of 9 +/-
      4.91 years at the time of their vaginal repair. The mean operative time was 82 +/
      47 minutes, with cases ranging from 37-182 minutes, with a median blood loss of
      7 mL and an average hospital stay of 1.2 days. There were no surgical
      complications. CONCLUSION: Neurosurgeons and otolaryngologists have been
      optimizing safe visualization of small areas during surgery for years with the
      use of the LM. In cases of pediatric deep genital trauma, the LM can be used
      safely for easy visualization, allowing for direct visualization in cases of deep
      genital trauma.

PMID- 24581678
TI  - Phylogeny of the Rhizobium-Allorhizobium-Agrobacterium clade supports the
      delineation of Neorhizobium gen. nov.
AB  - The genera Agrobacterium, Allorhizobium, and Rhizobium belong to the family
      Rhizobiaceae. However, the placement of a phytopathogenic group of bacteria, the
      genus Agrobacterium, among the nitrogen-fixing bacteria and the unclear position
      of Rhizobium galegae have caused controversy in previous taxonomic studies. To
      resolve uncertainties in the taxonomy and nomenclature within this family, the
      phylogenetic relationships of generic members of Rhizobiaceae were studied, but
      with particular emphasis on the taxa included in Agrobacterium and the "R.
      galegae complex" (R. galegae and related taxa), using multilocus sequence
      analysis (MLSA) of six protein-coding housekeeping genes among 114 rhizobial and
      agrobacterial taxa. The results showed that R. galegae, R. vignae, R. huautlense,
      and R. alkalisoli formed a separate clade that clearly represented a new genus,
      for which the name Neorhizobium is proposed. Agrobacterium was shown to represent
      a separate cluster of mainly pathogenic taxa of the family Rhizobiaceae. A. vitis
      grouped with Allorhizobium, distinct from Agrobacterium, and should be
      reclassified as Allorhizobium vitis, whereas Rhizobium rhizogenes was considered
      to be the proper name for former Agrobacterium rhizogenes. This phylogenetic
      study further indicated that the taxonomic status of several taxa could be
      resolved by the creation of more novel genera. 

PMID- 24581679
TI  - Characterization of a new marine nitrite oxidizing bacterium, Nitrospina watsonii
      sp. nov., a member of the newly proposed phylum "Nitrospinae".
AB  - Nitrite oxidizing bacteria are an integral part of the nitrogen cycle in marine
      waters, but the knowledge about their diversity is limited. Recently, a high
      abundance of Nitrospina-like 16S rRNA gene sequences has been detected in oceanic
      habitats with low oxygen content by molecular methods. Here, we describe a new
      strain of Nitrospina, which was sampled in 100m depth from the Black Sea. It
      coexisted with a not-yet cultivated chemoorganotrophic gammaproteobacterium and
      could be purified by classical isolation methods including Percoll density
      gradient centrifugation. The new Nitrospina-like bacterium grew
      lithoautotrophically at 28 degrees C in diluted seawater supplemented with
      inorganic salts and nitrite. Gram-negative rods were characterized
      morphologically, physiologically and partly biochemically. The 16S rRNA gene of
      the new strain of Nitrospina is 97.9% similar to the described species N.
      gracilis and DNA/DNA hybridization experiments revealed a relatedness of 30.0%.
      The data from both Nitrospina species and environmental clones were used for an
      extensive 16S rRNA based phylogenetic study applying high quality filtering.
      Treeing analyses confirm the newly defined phylum status for "Nitrospinae" [18].
      The results of phylogenetic and genotypic analyses support the proposal of a
      novel species Nitrospina watsonii sp. nov. (type strain 347(T), LMG 27401(T),
      NCIMB 14887(T)). 

PMID- 24581680
TI  - The effect of an educational intervention to improve patient antibiotic adherence
      during dispensing in a community pharmacy.
AB  - OBJECTIVE: To assess the effectiveness of an educational intervention on
      antibiotic adherence and patient-reported resolution of symptoms. DESIGN: A
      controlled experimental study with systematic assignment to groups. SETTING: A
      pharmacy in Murcia. Participants were patients who came to the pharmacy with a
      prescription for antibiotics. Intervention provided information on treatment
      characteristics (duration, dose and method of use) and correct compliance. A
      control group received routine care. Main variables "treatment adherence" and
      "perceived health" were evaluated one week after dispensation by telephone
      interview. RESULTS: A total of 126 patients completed the study, 62 in the
      Control Group (CG) and 64 in the Intervention Group (IG). There were no
      differences between the groups in baseline characteristics, including the level
      of knowledge before the intervention. At the end of the study, treatment
      adherence in the CG was 48.4% (CI: 36.4-60.6), compared with 67.2% (CI: 55.0
      77.4) in the IG. The difference of 18.8% was statistically significant (p=0.033;
      95% CI=15.8-34.6). Non-compliance through missing more than one dose was 81.2% in
      the CG versus 38.1% in the IG, which is a statistically significant difference of
      43.1% (p=0.001; 95% CI=16.4-63.1%). No significant differences were found in
      patient-perceived health. Logistic regression showed as predictor of adherence,
      the medication knowledge and the coincidence between duration of treatment
      indicated by physician and duration of treatment written in the prescription.
      CONCLUSIONS: An educational intervention during antibiotic dispensation improves
      treatment adherence versus routine care.

PMID- 24581681
TI  - Nurse staffing and education in Europe: if not now, when?

PMID- 24581684
TI  - Poultry carrying H9N2 act as incubators for novel human avian influenza viruses.

PMID- 24581682
TI  - Cholangiocarcinoma.
AB  - Cholangiocarcinoma represents a diverse group of epithelial cancers united by
      late diagnosis and poor outcomes. Specific diagnostic and therapeutic approaches
      are undertaken for cholangiocarcinomas of different anatomical locations
      (intrahepatic, perihilar, and distal). Mixed hepatocellular cholangiocarcinomas
      have emerged as a distinct subtype of primary liver cancer. Clinicians need to be
      aware of intrahepatic cholangiocarcinomas arising in cirrhosis and properly
      assess liver masses in this setting for cholangiocarcinoma. Management of biliary
      obstruction is obligatory in perihilar cholangiocarcinoma, and advanced
      cytological tests such as fluorescence in-situ hybridisation for aneusomy are
      helpful in the diagnosis. Liver transplantation is a curative option for selected
      patients with perihilar but not with intrahepatic or distal cholangiocarcinoma.
      International efforts of clinicians and scientists are helping to identify the
      genetic drivers of cholangiocarcinoma progression, which will unveil early
      diagnostic markers and direct development of individualised therapies. 

PMID- 24581685
TI  - Japanese Board Certification System for head and neck surgeons.
AB  - The Japan Society for Head and Neck Surgery (JSHNS) started a board certification
      system for head and neck surgeons in 2010. To become certified, the following
      qualification and experiences are required: (1) board certification as
      otorhinolaryngologist, (2) 2 years of clinical experience in a board-certified
      training facility, (3) clinical care of 100 patients with head and neck cancer
      under the supervision of board-certified faculty and (4) surgical experience in
      50 major head and neck surgical procedures, including 20 neck dissections, under
      the supervision of board-certified faculty. The following scientific activities
      are also required during the preceding 5 years: (1) two clinical papers on head
      and neck cancers presented at major scientific meetings, (2) one clinical paper
      on head and neck cancer published in a major journal, (3) attendance at two
      annual meetings of JSHNS and (4) enrolment in three educational programs approved
      by JSHNS. The qualifying examination consists of multiple choice tests and oral
      examinations. A total of 151 head and neck surgeons were certified in 2010
      followed by 43 in 2011 and 34 in 2012, while the membership of JSHNS dramatically
      increased from 1201 in 2007 to 1748 in 2013. Although the board certification
      system for head and neck surgeons was started only recently, it has encouraged
      many residents and fellows as well as established head and neck surgeons. We
      believe that this system will contribute to further advancement in the clinical
      practice for head and neck cancers in Japan. 

PMID- 24581683
TI  - Nurse staffing and education and hospital mortality in nine European countries: a
      retrospective observational study.
AB  - BACKGROUND: Austerity measures and health-system redesign to minimise hospital
      expenditures risk adversely affecting patient outcomes. The RN4CAST study was
      designed to inform decision making about nursing, one of the largest components
      of hospital operating expenses. We aimed to assess whether differences in patient
      to nurse ratios and nurses' educational qualifications in nine of the 12 RN4CAST
      countries with similar patient discharge data were associated with variation in
      hospital mortality after common surgical procedures. METHODS: For this
      observational study, we obtained discharge data for 422,730 patients aged 50
      years or older who underwent common surgeries in 300 hospitals in nine European
      countries. Administrative data were coded with a standard protocol (variants of
      the ninth or tenth versions of the International Classification of Diseases) to
      estimate 30 day in-hospital mortality by use of risk adjustment measures
      including age, sex, admission type, 43 dummy variables suggesting surgery type,
      and 17 dummy variables suggesting comorbidities present at admission. Surveys of
      26,516 nurses practising in study hospitals were used to measure nurse staffing
      and nurse education. We used generalised estimating equations to assess the
      effects of nursing factors on the likelihood of surgical patients dying within 30
      days of admission, before and after adjusting for other hospital and patient
      characteristics. FINDINGS: An increase in a nurses' workload by one patient
      increased the likelihood of an inpatient dying within 30 days of admission by 7%
      (odds ratio 1.068, 95% CI 1.031-1.106), and every 10% increase in bachelor's
      degree nurses was associated with a decrease in this likelihood by 7% (0.929,
      0.886-0.973). These associations imply that patients in hospitals in which 60% of
      nurses had bachelor's degrees and nurses cared for an average of six patients
      would have almost 30% lower mortality than patients in hospitals in which only
      30% of nurses had bachelor's degrees and nurses cared for an average of eight
      patients. INTERPRETATION: Nurse staffing cuts to save money might adversely
      affect patient outcomes. An increased emphasis on bachelor's education for nurses
      could reduce preventable hospital deaths. FUNDING: European Union's Seventh
      Framework Programme, National Institute of Nursing Research, National Institutes
      of Health, the Norwegian Nurses Organisation and the Norwegian Knowledge Centre
      for the Health Services, Swedish Association of Health Professionals, the
      regional agreement on medical training and clinical research between Stockholm
      County Council and Karolinska Institutet, Committee for Health and Caring
      Sciences and Strategic Research Program in Care Sciences at Karolinska
      Institutet, Spanish Ministry of Science and Innovation.

PMID- 24581686
TI  - Antibacterial effector/immunity systems: it's just the tip of the iceberg.
AB  - Bacteria do not live anchoretic; rather they are constantly in touch with their
      eukaryotic hosts and with other bacteria sharing their habitat. Therefore,
      bacteria have evolved sophisticated proteinaceous weapons. To harm other
      bacteria, they produce antibacterial effector proteins, which they either release
      into the environment or export via direct intercellular contact. Contact
      dependent killing is mediated by two specialized secretion systems, the type V
      and VI secretion system, whereas contact-independent processes hijack other
      transport mechanisms. Regardless of the transport system, cells co-express
      immunity proteins to protect themselves from suicide and fratricide. In general,
      effector protein activities and secretion mechanisms differ between Gram-positive
      and Gram-negative bacteria and evidence is emerging that different
      effector/immunity systems act synergistically and thus extend the bacterial
      armory. 

PMID- 24581687
TI  - Genetic systems for studying obligate intracellular pathogens: an update.
AB  - Rapid advancements in the genetic manipulation of obligate intracellular
      bacterial pathogens have been made over the past two years. In this paper we
      attempt to summarize the work published since 2011 that documents these exciting
      accomplishments. Although each genus comprising this diverse group of pathogens
      poses unique problems, requiring modifications of established techniques and the
      introduction of new tools, all appear amenable to genetic analysis.
      Significantly, the field is moving forward from a focus on the identification and
      development of genetic techniques to their application in addressing crucial
      questions related to mechanisms of bacterial pathogenicity and the requirements
      of obligate intracellular growth. 

PMID- 24581688
TI  - Macrophages clean up: efferocytosis and microbial control.
AB  - Phagocytic leukocytes, predominantly macrophages, not only ingest and destroy
      invading pathogens, but are charged with clearing dead and dying host cells. The
      process of engulfing apoptotic cells is called efferocytosis and has long been
      appreciated for its role in the resolution of inflammation. New evidence is
      emerging that efferocytosis represents a double-edged sword in microbial
      immunity. Although efferocytosis of influenza and Mycobacterium tuberculosis
      infected cells results in pathogen destruction, efferocytosis of Leishmania
      infected neutrophils may promote infection. Understanding how macrophages,
      dendritic cells (DC) and neutrophils process pathogens encased within a dying
      cell could lead to the development of novel therapeutics that simultaneously
      suppress inflammation and promote pathogen clearance. 

PMID- 24581689
TI  - Structural organisation of the type IV secretion systems.
AB  - Type IV secretion (T4S) systems are large dynamic nanomachines that transport
      DNAs and/or proteins through the membranes of bacteria. Because of their
      complexity and multi-protein organisation, T4S systems have been extremely
      challenging to study structurally. However in the past five years significant
      milestones have been achieved by X-ray crystallography and cryo-electron
      microscopy. This review describes some of the more recent advances: the
      structures of some of the protein components of the T4S systems and the complete
      core complex structure that was determined using electron microscopy. 

PMID- 24581690
TI  - Staphylococcus aureus toxins.
AB  - Staphylococcus aureus is a dangerous pathogen that causes a variety of severe
      diseases. The virulence of S. aureus is defined by a large repertoire of
      virulence factors, among which secreted toxins play a preeminent role. Many S.
      aureus toxins damage biological membranes, leading to cell death. In particular,
      S. aureus produces potent hemolysins and leukotoxins. Among the latter, some were
      recently identified to lyse neutrophils after ingestion, representing an
      especially powerful weapon against bacterial elimination by innate host defense.
      Furthermore, S. aureus secretes many factors that inhibit the complement cascade
      or prevent recognition by host defenses. Several further toxins add to this multi
      faceted program of S. aureus to evade elimination in the host. This review will
      give an overview over S. aureus toxins focusing on recent advances in our
      understanding of how leukotoxins work in receptor-mediated or receptor
      independent fashions. 

PMID- 24581691
TI  - Exploitation of host lipids by bacteria.
AB  - Bacteria that interact with eukaryotic cells have developed a variety of
      strategies to divert host lipids, or cellular processes driven by lipids, to
      their benefit. Host lipids serve as building blocks for bacterial membrane
      formation and as energy source. They promote the formation of specific
      microdomains, facilitating interactions with the host. Host lipids are also
      critical players in the entry of bacteria or toxins into cells, and, for bacteria
      growing inside parasitophorous vacuoles, in building a secure shelter. Bacterial
      dissemination is often dependent on enzymatic activities targeting host lipids.
      Finally, on a larger scale, long lasting parasitic association can disturb host
      lipid metabolism so deeply as to 'reprogram' it, as proposed in the case of
      Mycobacterium infection. 

PMID- 24581693
TI  - Listeria monocytogenes ActA: a new function for a 'classic' virulence factor.
AB  - Listeria monocytogenes (Lm) is ubiquitous and widespread in the environment. It
      is responsible for one of the most severe human foodborne infection. Lm is a
      facultative intracellular bacterium that can cross the intestinal barrier,
      disseminate via the bloodstream and reach the liver, spleen, central nervous
      system and fetus. The bacterial surface protein ActA is one of the most critical
      and best characterized virulence factors of Lm. It fulfills many essential
      functions within host cells, allowing Lm escape from autophagy and recruiting an
      actin polymerization complex that promotes Lm actin-based motility, cell-to-cell
      spread and dissemination within host tissues. We have recently shown that ActA
      also acts extracellularly. It mediates Lm aggregation and biofilm formation in
      vitro and in vivo, and long-term colonization of the gut lumen. This new property
      of ActA favors Lm transmission and may participate in the selective pressure on
      Lm to maintain ActA. 

PMID- 24581692
TI  - Maintenance of vacuole integrity by bacterial pathogens.
AB  - Many intracellular bacterial pathogens reside within a membrane-bound
      compartment. The biogenesis of these vacuolar compartments is complex, involving
      subversion of host cell secretory pathways by bacterial proteins. In recent years
      it has become clear that disruption of vacuole biogenesis may result in membrane
      rupture and escape of bacteria into the host cell cytosol. Correct modulation of
      the host cell cytoskeleton, signalling molecules such as small GTPases and the
      lipids of the vacuole membrane have all been shown to be critical in the
      maintenance of vacuole integrity. Increasing evidence suggests that vacuole
      rupture may result from aberrant mechanical forces exerted on the vacuole,
      possibly due to a defect in vacuole expansion. 

PMID- 24581694
TI  - Detection of cytosolic bacteria by inflammatory caspases.
AB  - The sanctity of the cytosolic compartment is rigorously maintained by a number of
      innate immune mechanisms. Inflammasomes detect signatures of microbial infection
      and trigger caspase-1 or caspase-11 activation, culminating in cytokine secretion
      and obliteration of the replicative niche via pyroptosis. Recent studies have
      examined inflammatory caspase responses to cytosolic bacteria, including
      Burkholderia, Shigella, Listeria, Francisella, and Mycobacterium species. For
      example, caspase-11 responds to LPS introduced into the cytosol after Gram
      negative bacteria escape the vacuole. Not surprisingly, bacteria antagonize these
      responses; for example, Shigella delivers OspC3 to inhibit caspase-4, a potential
      human homolog of murine caspase-11. These findings underscore bacterial
      coevolution with the innate immune system, which has resulted in few, but highly
      specialized cytosolic pathogens. 

PMID- 24581695
TI  - Emerging insights on intestinal dysbiosis during bacterial infections.
AB  - Infection of the gastrointestinal tract is commonly linked to pathological
      imbalances of the resident microbiota, termed dysbiosis. In recent years,
      advanced high-throughput genomic approaches have allowed us to examine the
      microbiota in an unprecedented manner, revealing novel biological insights about
      infection-associated dysbiosis at the community and individual species levels. A
      dysbiotic microbiota is typically reduced in taxonomic diversity and metabolic
      function, and can harbour pathobionts that exacerbate intestinal inflammation or
      manifest systemic disease. Dysbiosis can also promote pathogen genome evolution,
      while allowing the pathogens to persist at high density and transmit to new
      hosts. A deeper understanding of bacterial pathogenicity in the context of the
      intestinal microbiota should unveil new approaches for developing diagnostics and
      therapies for enteropathogens. 

PMID- 24581696
TI  - Galectins as bacterial sensors in the host innate response.
AB  - A number of galectin family members have been shown to play important roles in
      host defense against pathogens, and they are expressed by barrier tissues as well
      as immune cells. Galectins are present in the cytoplasm, nucleus, as well as
      extracellular space, and can function both inside and outside the cells.
      Galectins have been shown to bind to the surfaces of some pathogens and products
      released by the pathogens. These can result in either direct effects on growth of
      the pathogens or immune responses against them. Galectins may also affect the
      process of bacteria entering the host cells, such as adhesion. While galectin
      mediated sensing of bacterial infection demonstrated so far mainly takes place at
      the extracellular site, it can occur at the intracellular site, intracellular
      galectins can recognize some intracellular bacteria. In the latter case,
      galectins may bind to glycans on the surface of the bacteria or the host glycans
      displayed on the ruptured membranes of endosomes that initially contain the
      bacteria. Thus, galectins can play important roles inside the cells in response
      to infection by intracellular bacteria. 

PMID- 24581697
TI  - Impact of CRISPR immunity on the emergence and virulence of bacterial pathogens.
AB  - CRISPR-Cas systems protect prokaryotes from viruses and plasmids and function
      primarily as an adaptive immune system in these organisms. Recent discoveries,
      however, revealed unexpected roles for CRISPR loci as barriers to horizontal gene
      transfer and as modulators of gene expression. We review how both of these
      functions of CRISPR-Cas systems can affect the emergence and virulence of human
      bacterial pathogens. 

PMID- 24581699
TI  - Public-private partnerships with large corporations: setting the ground rules for
      better health.
AB  - Public-private partnerships with large corporations offer potential benefits to
      the health sector but many concerns have been raised, highlighting the need for
      appropriate safeguards. In this paper we propose five tests that public policy
      makers may wish to apply when considering engaging in such a public-private
      partnership. First, are the core products and services provided by the
      corporation health enhancing or health damaging? In some cases, such as tobacco,
      the answer is obvious but others, such as food and alcohol, are contested. In
      such cases, the burden of proof is on the potential partners to show that their
      activities are health enhancing. Second, do potential partners put their policies
      into practice in the settings where they can do so, their own workplaces? Third,
      are the corporate social responsibility activities of potential partners
      independently audited? Fourth, do potential partners make contributions to the
      commons rather than to narrow programmes of their choosing? Fifth, is the role of
      the partner confined to policy implementation rather than policy development,
      which is ultimately the responsibility of government alone? 

PMID- 24581698
TI  - Deciphering histone code of transcriptional regulation in malaria parasites by
      large-scale data mining.
AB  - Histone modifications play a major role in the regulation of gene expression.
      Accumulated evidence has shown that histone modifications mediate biological
      processes such as transcription cooperatively. This has led to the hypothesis of
      'histone code' which suggests that combinations of different histone
      modifications correspond to unique chromatin states and have distinct functions.
      In this paper, we propose a framework based on association rule mining to
      discover the potential regulatory relations between histone modifications and
      gene expression in Plasmodium falciparum. Our approach can output rules with
      statistical significance. Some of the discovered rules are supported by
      literature of experimental results. Moreover, we have also discovered de novo
      rules which can guide further research in epigenetic regulation of transcription.
      Based on our association rules we build a model to predict gene expression, which
      outperforms a published Bayesian network model for gene expression prediction by
      histone modifications. The results of our study reveal mechanisms for histone
      modifications to regulate transcription in large-scale. Among our findings, the
      cooperation among histone modifications provides new evidence for the hypothesis
      of histone code. Furthermore, the rules output by our method can be used to
      predict the change of gene expression. 

PMID- 24581700
TI  - Automation bias: empirical results assessing influencing factors.
AB  - OBJECTIVE: To investigate the rate of automation bias - the propensity of people
      to over rely on automated advice and the factors associated with it. Tested
      factors were attitudinal - trust and confidence, non-attitudinal - decision
      support experience and clinical experience, and environmental - task difficulty.
      The paradigm of simulated decision support advice within a prescribing context
      was used. DESIGN: The study employed within participant before-after design,
      whereby 26 UK NHS General Practitioners were shown 20 hypothetical prescribing
      scenarios with prevalidated correct and incorrect answers - advice was incorrect
      in 6 scenarios. They were asked to prescribe for each case, followed by being
      shown simulated advice. Participants were then asked whether they wished to
      change their prescription, and the post-advice prescription was recorded.
      MEASUREMENTS: Rate of overall decision switching was captured. Automation bias
      was measured by negative consultations - correct to incorrect prescription
      switching. RESULTS: Participants changed prescriptions in 22.5% of scenarios. The
      pre-advice accuracy rate of the clinicians was 50.38%, which improved to 58.27%
      post-advice. The CDSS improved the decision accuracy in 13.1% of prescribing
      cases. The rate of automation bias, as measured by decision switches from correct
      pre-advice, to incorrect post-advice was 5.2% of all cases - a net improvement of
      8%. More immediate factors such as trust in the specific CDSS, decision
      confidence, and task difficulty influenced rate of decision switching. Lower
      clinical experience was associated with more decision switching. Age, DSS
      experience and trust in CDSS generally were not significantly associated with
      decision switching. CONCLUSIONS: This study adds to the literature surrounding
      automation bias in terms of its potential frequency and influencing factors.

PMID- 24581701
TI  - Effects of plyometric and pneumatic explosive strength training on neuromuscular
      function and dynamic balance control in 60-70year old males.
AB  - The present study compared neuromuscular adaptations to 12weeks of plyometric
      (PLY) or pneumatic (PNE) power training and their effects on dynamic balance
      control. Twenty-two older adults aged 60-70 (PLY n=9, PNE n=11) participated in
      the study. Measurements were conducted at Pre, 4, 8 and 12weeks. Dynamic balance
      was assessed as anterior-posterior center of pressure (COP) displacement in
      response to sudden perturbations. Explosive isometric knee extension and plantar
      flexion maximal voluntary contractions (MVCs) were performed. Maximal drop jump
      performance from optimal dropping height was measured in a sledge ergometer.
      Increases in knee extensor and ankle plantar flexor torque and muscle activity
      were higher and occurred sooner in PNE, whereas in drop jumping, PLY showed a
      clearer increase in optimal drop height (24%, p<0.01) after 8weeks of training
      and soleus muscle activity after 12weeks of training. In spite of these training
      mode specific adaptations, both groups showed similar improvements in dynamic
      balance control after 4weeks of training (PLY 38%, p<0.001; PNE 31%, p<0.001) and
      no change thereafter. These results show that although power and plyometric
      training may involve different neural adaptation mechanisms, both training modes
      can produce similar improvements in dynamic balance control in older individuals.
      As COP displacement was negatively correlated with rapid knee extension torque in
      both groups (PLY r=-0.775, p<0.05; PNE r=-0.734, p<0.05) after training, the
      results also highlight the importance of targeting rapid force production when
      training older adults to improve dynamic balance.

PMID- 24581703
TI  - Factors affecting self-reported implementation of evidence-based practice among a
      group of dentists.
AB  - OBJECTIVE: The study aimed at assessing the factors affecting the implementation
      of evidence-based practice (EBP) among a group of dentists in Saudi Arabia.
      METHODS: A cross sectional study design was used where a link to an electronic
      questionnaire was posted on the websites of the Saudi Dental Society and a social
      networking site for dentists. The questionnaire was available for three months
      after which responses were downloaded and analyzed. Descriptive statistics were
      calculated for various variables and logistic regression analysis was used to
      identify factors with significant effect on the implementation of EBP. RESULTS:
      Implementation of EBP was reported by 69.3% of respondents. Most respondents
      reported knowing and using MEDLINE and being able to search for evidence. The
      most frequently reported barriers were lack of time and availability of evidence.
      Factors that significantly affected the implementation of EBP were 1) having some
      knowledge of terms related to EBP, 2) reporting lack of EBP skills as a barrier,
      and 3) reporting resistance to change as a barrier. CONCLUSIONS: Background
      knowledge related to EBP and training in its skills are needed for the
      implementation of EBP whereas the presence of resistance to change does not
      necessarily prevent its implementation.

PMID- 24581704
TI  - Assessing the reporting quality in abstracts of randomized controlled trials in
      leading journals of oral implantology.
AB  - AIM: Abstracts of randomized clinical trials are extremely important as trial
      appraisal is often based on the information included here. The objective of this
      study was to assess the quality of the reporting of RCT abstracts in journals of
      Oral Implantology. MATERIAL AND METHODS: Six leading Implantology journals were
      screened for RCTs between years 2008 and 2012. A 21-item modified CONSORT for
      abstracts checklist was used to examine the completeness of abstract reporting.
      Descriptive statistics and linear regression modeling were employed for data
      analysis. RESULTS: One hundred and sixty three RCT abstracts were included in
      this study. The majority of the RCTs were published in the Clinical Oral Implants
      Research (42.9%). The mean overall reporting quality score was 58.6% (95% CI:
      57.6-59.7). The highest score was noted in the European Journal of Oral
      Implantology (63.8%; 95% CI: 61.8-65.8). Multivariate analysis demonstrated that
      abstract quality score was related to publication journal and number of research
      centers involved. Most abstracts adequately reported interventions (89.0%),
      objectives (77.9%) and conclusions (74.8%) while failed to report randomization
      procedures, allocation concealment, effect estimate, confidence intervals, and
      funding. Registration of RCTs was not reported in any of the abstracts.
      CONCLUSIONS: The reporting quality in abstracts of RCTs published in Oral
      Implantology journals needs to be improved. Editors and authors should be
      encouraged to endorse the CONSORT for abstracts guidelines in order to achieve
      optimal quality in abstract reporting.

PMID- 24581705
TI  - Dental caries is related to obesity in children but the relationship is moderated
      by socio-economic strata and child age.

PMID- 24581702
TI  - Outcome markers for clinical trials in cerebral amyloid angiopathy.
AB  - Efforts are underway for early-phase trials of candidate treatments for cerebral
      amyloid angiopathy, an untreatable cause of haemorrhagic stroke and vascular
      cognitive impairment. A major barrier to these trials is the absence of consensus
      on measurement of treatment effectiveness. A range of potential outcome markers
      for cerebral amyloid angiopathy can be measured against the ideal criteria of
      being clinically meaningful, closely representative of biological progression,
      efficient for small or short trials, reliably measurable, and cost effective. In
      practice, outcomes tend either to have high clinical salience but low statistical
      efficiency, and thus more applicability for late-phase studies, or greater
      statistical efficiency but more limited clinical meaning. The most statistically
      efficient markers might be those that are potentially reversible with treatment,
      although their clinical significance remains unproven. Many of the candidate
      outcomes for cerebral amyloid angiopathy trials are probably applicable also to
      other small-vessel brain diseases. 

PMID- 24581706
TI  - Implant survival rates may not exceed those of compromised but adequately treated
      and maintained teeth.

PMID- 24581707
TI  - Guided tissue regeneration (GTR) with bioabsorbable collagen membranes (CM) may
      generate more clinical attachment level gain than open flap debridement (OFD).

PMID- 24581708
TI  - Dental therapists provide technically competent clinical care when performing
      irreversible restorative procedures.

PMID- 24581709
TI  - A high-viscosity GIC sealant increases the fluoride concentration in
      interproximal fluid more than a resin-based sealant containing fluoride.

PMID- 24581710
TI  - Scaling and root-planing (SRP) may improve glycemic control and lipid profile in
      patients with chronic periodontitis (CP) and type 2 diabetes (DM2) in a specific
      subgroup: a meta-analysis of randomized clinical trials.

PMID- 24581711
TI  - Amoxicillin and 0.12% chlorhexidine mouthwash may not be better than placebo for
      reducing bacteremia in third molar extractions.

PMID- 24581712
TI  - School-based dental programs prevent dental caries in children at high risk for
      caries from low socioeconomic backgrounds.

PMID- 24581713
TI  - Vitamin D may reduce periodontal disease prevalence in older men.

PMID- 24581714
TI  - Arginine metabolism in dental plaque is associated with tooth surface dental
      caries status.

PMID- 24581715
TI  - Disutility analysis of oil spills: graphs and trends.
AB  - This paper reports the results of an analysis of oil spill cost data assembled
      from a worldwide pollution database that mainly includes data from the
      International Oil Pollution Compensation Fund. The purpose of the study is to
      analyze the conditions of marine pollution accidents and the factors that impact
      the costs of oil spills worldwide. The accidents are classified into categories
      based on their characteristics, and the cases are compared using charts to show
      how the costs are affected under all conditions. This study can be used as a
      helpful reference for developing a detailed statistical model that is capable of
      reliably and realistically estimating the total costs of oil spills. To
      illustrate the differences identified by this statistical analysis, the results
      are compared with the results of previous studies, and the findings are
      discussed. 

PMID- 24581716
TI  - Mercury speciation in coastal sediments from the central east coast of India by
      modified BCR method.
AB  - This is the first study to describe distribution and speciation of Hg in coastal
      sediments from the central east coast of India. The concentrations of Hg in the
      studied sediments were found to be much lower than the Hg concentration
      recommended in coastal sediments by the United State Environmental Protection
      Agency and the Canadian Council of Ministers of the Environment for the
      protection of aquatic life. This study suggests that the interactions between Hg
      and coastal sediments are influenced by particle size (sand, silt and clay) of
      the sediments and the total organic carbon (TOC) content in the sediments. It was
      found that the coastal sediments from the central east coast of India could act
      as a sink for Hg. The availability of strong uncomplexed-Hg binding sites in the
      coastal sediments was observed. 

PMID- 24581717
TI  - Attention deficit hyperactivity disorder and sleep disordered breathing in
      pediatric populations: a meta-analysis.
AB  - A relationship between attention deficit hyperactivity disorder (ADHD) and sleep
      disordered breathing (SDB) in children and adolescents has been suggested by some
      authors. Yet, this topic remains highly controversial in the literature. A meta
      analysis was conducted in order to examine the extent of relationship between SDB
      and ADHD symptoms in pediatric populations and whether there are differences in
      ADHD symptoms pre- versus post-adenotonsillectomy in pediatric populations.
      PubMed/Medline, PsychInfo and Cochrane databases were searched using the key
      words "attention deficit hyperactivity disorder" or "ADHD" and "obstructive sleep
      apnea" or "OSA" or "sleep disordered breathing" (SDB) or "SDB". English language
      publications through September 2012 were surveyed. Meta-analysis was conducted to
      assess the relationship between SDB and ADHD symptoms in the first part of the
      study, and the extent of change in ADHD symptoms before and after
      adenotonsillectomy in the second part. Eighteen studies satisfied the inclusion
      criteria for the first part of the study. This represented 1113 children in the
      clinical group (874 diagnosed with SDB who were examined for ADHD symptoms; 239
      diagnosed with ADHD who were examined for SDB) and 1405 in the control-group.
      Findings indicate that there is a medium relationship between ADHD symptoms and
      SDB (Hedges' g = 0.57, 95% confidence interval: 0.36-0.78; p = 0.000001). A high
      apnea hypopnea index (AHI) cutoff was associated with lower effect sizes, while
      child age, gender and body mass index did not moderate the relationship between
      SDB and ADHD. Study quality was associated with larger effect sizes. In the
      second part of the study, twelve studies were identified assessing pre- versus
      post-surgery ADHD symptoms. Hedges' g was 0.43 (95% confidence interval = 0.30
      0.55; p < 0.001; N = 529) suggesting a medium effect, as adenotonsillectomy was
      associated with decreased ADHD symptoms at 2-13 months post-surgery. The findings
      of this meta-analysis suggest that ADHD symptoms are related to SDB and improve
      after adenotonsillectomy. Therefore, patients with ADHD symptomatology should
      receive SDB screening. Treatment of comorbid SDB should be considered before
      medicating the ADHD symptoms if present.

PMID- 24581718
TI  - What is known about the experiences of using CPAP for OSA from the users'
      perspective? A systematic integrative literature review.
AB  - Economic, social and personal costs of untreated obstructive sleep apnoea (OSA)
      are high. Continuous positive airway pressure (CPAP) is recommended and cost
      effective. Increasing OSA prevalence may accompany predicted globally increasing
      obesity. OBJECTIVE: To synthesise international evidence regarding personal
      experiences using CPAP for OSA. METHODS: A systematic integrative literature
      review was conducted and quality assessment criteria applied. RESULTS: 22, of
      538, identified papers met inclusion criteria. Thematic analysis identified three
      themes: 1) users' beliefs about CPAP influence users' experiences of CPAP; 2)
      CPAP users are primed to reflect negatively on experiences of CPAP; and 3) spouse
      and family influence users' experiences of CPAP. Personality and attitude impact
      expectations about CPAP prior to use, whilst engagement of spouse and family also
      influence experiences. Analysis highlighted that users' reporting of CPAP
      experiences is constrained by investigator defined assessment methods. Overall,
      research relating to experiences using CPAP is limited. CONCLUSION: Users'
      perspectives of CPAP are constrained by researchers' concern with non-compliance.
      Typically experiences are not defined by the user, but from an 'expert'
      healthcare perspective, using words which frame CPAP as problematic. Family and
      social support is a significant, but neglected area of experiencing CPAP
      warranting further investigation. More information from users is required to
      determine how CPAP can be managed successfully.

PMID- 24581719
TI  - Dual antiplatelet therapy after coronary artery bypass grafting: does off/on-pump
      play a role?

PMID- 24581720
TI  - Marijuana smoking is associated with atrial fibrillation.

PMID- 24581721
TI  - Adverse cardiovascular, cerebrovascular, and peripheral vascular effects of
      marijuana: what cardiologists need to know.

PMID- 24581722
TI  - 1082-39, an analogue of sorafenib, inhibited human cancer cell growth more
      potently than sorafenib.
AB  - PURPOSE: 1082-39, an analogue of sorafenib, is a derivative of indazole
      diarylurea. We evaluated the activity of 1082-39 against human cancer cell
      growth. Its effects and mechanisms of action were then compared with those of
      sorafenib. The experiments were performed in human melanoma M21 cells. METHODS:
      Cell viability was estimated by using the colorimetric assay. Annexin V-FITC/PI
      staining assay was used to recognize the apoptotic cells. Further analysis of the
      mitochondria membrane potential (MMP) was performed by the JC-1 fluorescence
      probe staining. The levels of apoptotic proteins and kinases related to cancer
      proliferation were determined by western blotting assay. RESULTS: 1082-39
      possessed the activity against cancer cell proliferation with time- and dose
      dependent manner. 1082-39 induced M21 cell to apoptosis, showing the increase of
      annexin V-FITC/PI staining cells, the MMP collapse and releasing cytochrome c
      from mitochondria. Western blotting analysis showed the activation of the
      mitochondria-mediated intrinsic pathway, showing the increase of cleaved caspase
      9, cleaved caspase-3 and cleaved PARP. Statistical analysis suggested that 1082
      39 possessed greater activities than sorafenib in the inhibition of M21
      proliferation and induction of apoptosis. These effects of 1082-39 might arise
      from its activity of regulation the PI3K/Akt and Wnt/beta-catenin signaling
      pathways. CONCLUSIONS: 1082-39 is a promising candidate compound which could
      develop as a potent anticancer agent.

PMID- 24581723
TI  - Pre-adjuvant chemotherapy leukocyte count may predict the outcome for advanced
      gastric cancer after radical resection.
AB  - Gastric cancer (GC) has a high morbidity worldwide each year especially in China
      and advanced GC is well known with poor prognosis, for which surgical resection
      combine adjuvant chemotherapy is the optimal choice for therapy. Leukocyte is an
      important index during the treatment for its influence on drugs' dosage and
      tolerance. Therefore, peripheral blood leukocyte and its subsets during adjuvant
      chemotherapy may have great clinical value for predicting prognostic. In this
      retrospective study, we showed the distribution of white blood cell and its
      subsets in the baseline period before adjuvant chemotherapy in 399 patients who
      underwent radical resection for advanced GC from January 1, 2008 to August 31,
      2012. We investigated the relationship between leukocyte count and overall
      survival (OS) as well as disease-free survival (DFS). In these patients, females
      were more likely to have less white blood cells after operation (P=0.016).
      Patients with pre-chemotherapy leukocyte count less than 4*10(9)/L got worse DFS
      (P=0.028) and OS (P=0.016). In multivariate analysis, tumor size >= 6cm
      (P=0.033), TNM stage IV (P=0.024), vascular or nerval invasion (P=0.005) and
      leukocyte count less than 4.0*10(9)/L (P=0.019) was associated with poor DFS. TNM
      stage IV (P=0.008), vascular or nerval invasion (P=0.001) and lower leukocyte
      count (P=0.045) were independent risk factors for poor OS. Taken together, our
      findings suggest that pre-adjuvant chemotherapy peripheral blood leukocyte count
      correlates with clinical outcome of patients with advanced GC after radical
      resection. 

PMID- 24581724
TI  - Formation of vasculogenic mimicry in bone metastasis of prostate cancer:
      correlation with cell apoptosis and senescence regulation pathways.
AB  - Vasculogenic mimicry (VM) has been found in prostate cancer (PCa) as an
      independent marker of poor prognosis. To investigate the correlation between VM
      and bone metastasis in PCa, a total of 80 cases were analyzed by CD31 and PAS
      dual-staining as well as the follow-up data. All cases were divided into two
      groups: VM-positive and VM-negative (VM-pos/VM-neg). Immunohistochemical staining
      for investigating the expression of Casepase-3, Bcl-2/Bax, and SA-beta-gal was
      performed. 28 of the 80 PCa cases exhibited VM structure (35.0%). The incidence
      of bone metastasis in the VM-pos and VM-neg was 67.9% (19/28) and 38.5% (20/52),
      respectively. The positive rate of Casepase-3 and Bcl-2 expression was
      significantly different of the two groups (Caspases-3: VM-pos 71.4%, 20/28 vs VM
      neg 42.3%, 22/52; Bcl-2: VM-pos 35.7%, 10/28 vs VM-neg 65.4%, 34/52). Bcl-2/Bax
      ratio of the VM-pos (0.71+/-0.22) was lower than that of the VM-pos (0.89+/
      0.13). In addition, a higher frequency of SA-beta-gal was detected in VM-pos
      (64.29+/-86.42) than in VM-neg (25.37+/-72.21). Taken together, our findings
      demonstrate that PCa with VM has the tendency to develop bone metastasis.
      Activations of cell apoptosis and senescence regulation pathways may play
      important roles in the formation process of VM structure. 

PMID- 24581726
TI  - A new vascular coupling device: assessment of MRI issues at 3-tesla.
AB  - OBJECTIVE: Vascular grafting frequently involves a time-consuming operation. A
      new vascular coupling device (VCD) made from metallic material was recently
      developed that may be advantageous because of the reduced operative time and
      decreased patient risks. Because of the metal, there are safety concerns related
      to MRI. Therefore, the purpose of this investigation was to use standardized
      testing techniques to evaluate MRI issues for this VCD in association with a 3
      Tesla MR system. METHODS: The VCD (corlife oHG, Hannover, Germany) was evaluated
      for magnetic field interactions (translational attraction and torque), MRI
      related heating, and artifacts at 3-Tesla. MRI-related heating was assessed with
      the VCD in a gelled-saline-filled phantom with MRI performed at a whole body
      averaged SAR of 2.9-W/kg for 15-min. Artifacts were assessed using T1-weighted,
      spin echo, and gradient echo pulse sequences. RESULTS: The VCD exhibited minor
      magnetic field interactions and minimal heating (maximum temperature elevation,
      1.8 degrees C). Artifacts were relatively small in relation to the size and shape
      of this implant. The lumen of the VCD could not be visualized using the gradient
      echo pulse sequence. CONCLUSIONS: The metallic VCD that underwent evaluation is
      MR conditional for a patient undergoing an MRI procedure at 3-Tesla or less.

PMID- 24581725
TI  - Mapping phosphorylation rate of fluoro-deoxy-glucose in rat brain by (19)F
      chemical shift imaging.
AB  - (19)F magnetic resonance spectroscopy (MRS) studies of 2-fluoro-2-deoxy-d-glucose
      (FDG) and 2-fluoro-2-deoxy-d-glucose-6-phosphate (FDG-6P) can be used for
      directly assessing total glucose metabolism in vivo. To date, (19)F MRS
      measurements of FDG phosphorylation in the brain have either been achieved ex
      vivo from extracted tissue or in vivo by unusually long acquisition times.
      Electrophysiological and functional magnetic resonance imaging (fMRI)
      measurements indicate that FDG doses up to 500 mg/kg can be tolerated with
      minimal side effects on cerebral physiology and evoked fMRI-BOLD responses to
      forepaw stimulation. In halothane-anesthetized rats, we report localized in vivo
      detection and separation of FDG and FDG-6P MRS signals with (19)F 2D chemical
      shift imaging (CSI) at 11.7 T. A metabolic model based on reversible transport
      between plasma and brain tissue, which included a non-saturable plasma to tissue
      component, was used to calculate spatial distribution of FDG and FDG-6P
      concentrations in rat brain. In addition, spatial distribution of rate constants
      and metabolic fluxes of FDG to FDG-6P conversion were estimated. Mapping the rate
      of FDG to FDG-6P conversion by (19)F CSI provides an MR methodology that could
      impact other in vivo applications such as characterization of tumor
      pathophysiology. 

PMID- 24581727
TI  - Arterial embolization in idiopathic spontaneous intra-peritoneal hemorrhage: case
      report and review.

PMID- 24581728
TI  - Dual-energy contrast-enhanced digital mammography: examination protocol.

PMID- 24581729
TI  - Potentiating maternal immune tolerance in pregnancy: a new challenging role for
      regulatory T cells.
AB  - The maternal immune system needs to adapt to tolerate the semi-allogeneic
      conceptus. Since maternal allo-reactive lymphocytes are not fully depleted, other
      local/systemic mechanisms play a key role in altering the immune response. The
      Th1/Th2 cytokine balance is not essential for a pregnancy to be normal. The
      immune cells, CD4+CD25+Foxp3+, also known as regulatory T cells (Tregs), step in
      to regulate the allo-reactive Th1 cells. In this review we discuss the role of
      Tregs in foeto-maternal immune tolerance and in recurrent miscarriage as well as
      their potential use as a new target for infertility treatment. Animal and human
      experiments showed Treg cell number and/or function to be diminished in
      miscarriages. Murine miscarriage can be prevented by transferring Tregs from
      normal pregnant mice. Tregs at the maternal-fetal interface prevented fetal allo
      rejection by creating a "tolerant" microenvironment characterised by the
      expression of IL-10, TGF-beta and haem oxygenase isoform 1 (HO-1) rather than by
      lowering Th1 cytokines. Tregs increase placental HO-1. In turn, HO-1 may lead to
      up-regulation of TGF-beta, IL-10 and CTLA-4. In vivo experiments showed Tregs
      sensitisation from paternal antigens to be essential for maternal-fetal
      tolerance. Tregs increase throughout pregnancy and diminish in late puerperium.
      Recent data also support the capacity of Tregs to block maternal effector T
      cells, thereby reducing the maternal-fetal pathological responses to paternal
      antigens. These findings also permit us to consider new strategies for improving
      pregnancy outcomes, i.e., anti-TNF blockers and granulocyte-colony stimulating
      factors as well as novel approaches to therapeutically exploiting Treg + cell
      memory.

PMID- 24581730
TI  - Extracellular traps in lipid-rich lesions of carotid atherosclerotic plaques:
      implications for lipoprotein retention and lesion progression.
AB  - PURPOSE: To investigate the presence and location of extracellular traps (ETs) in
      atherosclerotic plaques and to determine whether they are spatially associated
      with inflammatory cells and the lipid core. MATERIALS AND METHODS: Human carotid
      atherosclerotic plaques were collected from seven patients after surgical
      endarterectomy. Sequential tissue sections were stained with hematoxylin-eosin or
      subjected to immunohistochemistry to detect ETs, neutrophils and macrophages or
      apolipoprotein B (ApoB). To demonstrate the specificity of the antibody used to
      detect ETs, the adjacent tissue section was pretreated with deoxyribonuclease-1
      (DNase-1) before immunostaining for ETs. RESULTS: All seven carotid plaques
      demonstrated advanced atherosclerotic lesions. Extensive ET and ApoB
      immunostaining was detected predominantly within the acellular lipid core. Along
      the edges of the lipid core, confocal microscopy revealed areas suggestive of
      active release of ETs from MPO-positive cells. Pretreatment of tissue sections
      with DNase-1 abolished ET signal in the extracellular matrix, but not the signal
      within the cells along the margins of the core. CONCLUSIONS: The localization of
      ETs to the lipid core suggests a possible binding site for lipoproteins, which
      may further promote lesion progression and inflammation.

PMID- 24581732
TI  - Regional differences in post-traumatic stress symptoms among children after the
      2011 tsunami in Higashi-Matsushima, Japan.
AB  - INTRODUCTION: On 11 March 2011, a massive undersea earthquake, measuring 9.0 on
      the Richter scale, caused a tsunami that devastated the shoreline of east Japan.
      It is estimated that over 20,000 people lost their lives as a result. It is
      recommended that clinical effort after a tsunami disaster concentrate on a high
      impact area rather than cover a large area. However, regional differences in post
      traumatic stress symptoms among children after a tsunami disaster are not well
      clarified. METHODS: This study evaluated post-traumatic stress symptoms and
      reported the findings of early-phase screening of 2259 students from Higashi
      Matsushima City, Japan, 6 weeks after a tsunami hit the city. The sample was
      divided into two age groups: elementary school students (n=1102) and junior high
      school students (n=1157). Of these groups, 289 (26.2%) elementary school students
      and 123 (10.6%) junior high school students attended the four schools that were
      located in the area struck by the tsunami; the mortality rate of the area
      exceeded 4%. We referred to these students as the "high-impact group." The "lower
      impact group" consisted of 813 (73.8%) elementary school students and 1034
      (89.4%) junior high school students who attended the remaining ten schools.
      RESULTS: The severity of post-traumatic stress symptoms did not significantly
      differ between areas with relatively high and low impact. However, among the
      junior high school students, those attending the school in the highly impacted
      area showed higher post-traumatic symptoms scores than did the students of the
      less-impacted area. CONCLUSION: When planning a mass intervention after a
      disaster, especially in the early phase when the resources for intervention are
      not sufficient, it might be useful to consider the degree of age-dependent impact
      effect.

PMID- 24581733
TI  - Fast detection of high-order epistatic interactions in genome-wide association
      studies using information theoretic measure.
AB  - There are many algorithms for detecting epistatic interactions in GWAS. However,
      most of these algorithms are applicable only for detecting two-locus
      interactions. Some algorithms are designed to detect only two-locus interactions
      from the beginning. Others do not have limits to the order of interactions, but
      in practice take very long time to detect higher order interactions in real data
      of GWAS. Even the better ones take days to detect higher order interactions in
      WTCCC data. We propose a fast algorithm for detection of high order epistatic
      interactions in GWAS. It runs k-means clustering algorithm on the set of all
      SNPs. Then candidates are selected from each cluster. These candidates are
      examined to find the causative SNPs of k-locus interactions. We use mutual
      information from information theory as the measure of association between
      genotypes and phenotypes. We tested the power and speed of our method on
      extensive sets of simulated data. The results show that our method has more or
      equal power, and runs much faster than previously reported methods. We also
      applied our algorithm on each of seven diseases in WTCCC data to analyze up to 5
      locus interactions. It takes only a few hours to analyze 5-locus interactions in
      one dataset. From the results we make some interesting and meaningful
      observations on each disease in WTCCC data. In this study, a simple yet powerful
      two-step approach is proposed for fast detection of high order epistatic
      interaction. Our algorithm makes it possible to detect high order epistatic
      interactions in GWAS in a matter of hours on a PC. 

PMID- 24581731
TI  - Prostate biopsy for the interventional radiologist.
AB  - Prostate biopsies are usually performed by urologists in the office setting using
      transrectal ultrasound (US) guidance. The current standard of care involves
      obtaining 10-14 cores from different anatomic sections. Biopsies are usually not
      directed into a specific lesion because most prostate cancers are not visible on
      transrectal US. Color Doppler, US contrast agents, elastography, magnetic
      resonance (MR) imaging, and MR imaging/US fusion are proposed as imaging methods
      to guide prostate biopsies. Prostate MR imaging and fusion biopsy create
      opportunities for diagnostic and interventional radiologists to play an
      increasingly important role in the screening, evaluation, diagnosis, targeted
      biopsy, surveillance, and focal therapy of patients with prostate cancer. 

PMID- 24581735
TI  - Clinical and neuroimaging characteristics of 14 patients with prionopathy: a
      descriptive study.
AB  - INTRODUCTION: Prionopathy is the cause of 62% of the rapidly progressive
      dementias (RPD) in which a definitive diagnosis is reached. The variability of
      symptoms and signs exhibited by the patients, as well as its different
      presentation, sometimes makes an early diagnosis difficult. METHODS: Patients
      withdiagnosis of definite or probable prionopathy during the period 1999-2012 at
      our hospital were retrospectively reviewed.The clinical features and the results
      of the complementary tests (14-3-3 protein, EEG, MRI, FDG-PET, and genetic
      analysis) were evaluated in order to identify some factors that may enable an
      earlier diagnosis to be made. RESULTS: A total of 14 patients are described: 6
      with definite sporadic Creutzfeldt-Jakob (sCJD) disease, 3 with probable sCJD, 4
      with fatal familial insomnia, and 1 with the new variant. The median age at
      diagnosis was 54 years old. The mean survival was 9.5 months. Mood disorder was
      the most common feature, followed by instability and cognitive impairment. 14-3-3
      protein content in the cerebrospinal fluid was positive in 7 of 11 patients, and
      the EEG showed typical signs in 2 of 12 patients. Neuroimaging (FDG-PET, MRI)
      studies suggested the diagnosis in 13 of the 14 patients included. CONCLUSIONS:
      Most patients presenting with RPD suffer from a prion disease. In our series the
      most useful complementary tests were MRI and FDG-PET, being positive in 13 of the
      14 patients studied.

PMID- 24581734
TI  - Neural activation during response inhibition in adult attention
      deficit/hyperactivity disorder: preliminary findings on the effects of medication
      and symptom severity.
AB  - Studies of adults with attention-deficit/hyperactivity disorder (ADHD) have
      suggested that they have deficient response inhibition, but findings concerning
      the neural correlates of inhibition in this patient population are inconsistent.
      We used the Stop-Signal task and functional magnetic resonance imaging (fMRI) to
      compare neural activation associated with response inhibition between adults with
      ADHD (N=35) and healthy comparison subjects (N=62), and in follow-up tests to
      examine the effect of current medication use and symptom severity. There were no
      differences in Stop-Signal task performance or neural activation between ADHD and
      control participants. Among the ADHD participants, however, significant
      differences were associated with current medication, with individuals taking
      psychostimulants (N=25) showing less stopping-related activation than those not
      currently receiving psychostimulant medication (N=10). Follow-up analyses
      suggested that this difference in activation was independent of symptom severity.
      These results provide evidence that deficits in inhibition-related neural
      activation persist in a subset of adult ADHD individuals, namely those
      individuals currently taking psychostimulants. These findings help to explain
      some of the disparities in the literature, and advance our understanding of why
      deficits in response inhibition are more variable in adult, as compared with
      child and adolescent, ADHD patients. 

PMID- 24581736
TI  - Characteristics of breast carcinoma cases with false-negative sentinel lymph
      nodes.
AB  - BACKGROUND: In the past decade, sentinel lymph node biopsy (SLNB) has become
      standard for patients with early-stage clinically node-negative breast carcinoma
      (BC). Despite high overall surgical identification success rates with
      introduction of the dual-tracer techniques (dye and radiolabeled probe), false
      negative rates remained unchanged in most recent meta-analyses. PATIENTS AND
      METHODS: We analyzed cases with false-negative SLN biopsy results over a 12-year
      period in a single institution to evaluate their clinicopathologic
      characteristics. Sixty-three false-negative cases (3.1%) were found in 2043
      successful SLN mapping procedures, all of which were followed by varying amounts
      of additional axillary sampling. RESULTS: There was a higher proportion of
      invasive lobular carcinomas (ILCs; 23 cases [37%]) when compared with this
      lesion's overall reported frequency (5%-15%). The majority of invasive ductal
      carcinoma (IDC) cases (31 of 40) were poorly differentiated. In 80% of the ductal
      type cases, 1 or more nonsentinel nodes (NSLNs) were completely or partially
      replaced by tumor, as opposed to less than half of such cases of the lobular
      type. Twenty-two cases had multiple positive NSLN metastases, which were
      significantly associated with larger tumor size (>= 1.0 cm) and tumor replacement
      of NSLNs. Eighty-two percent of the cases with known hormone receptor status were
      positive for estrogen or progesterone receptors, or both. CONCLUSION: False
      negative SLN biopsy results were more often associated with a primary BC
      characterized by a lobular or poorly differentiated ductal histologic type or
      partial to complete replacement of NSLNs with tumor, or both.

PMID- 24581737
TI  - Comments on an alternative calculation of cytomegalovirus IgG avidity indexes on
      VIDAS.

PMID- 24581738
TI  - [Bilateral bacterial keratitis following photorefractive keratectomy].

PMID- 24581739
TI  - An expressed retrogene of the master embryonic stem cell gene POU5F1 is
      associated with prostate cancer susceptibility.
AB  - Genetic association studies of prostate and other cancers have identified a major
      risk locus at chromosome 8q24. Several independent risk variants at this locus
      alter transcriptional regulatory elements, but an affected gene and mechanism for
      cancer predisposition have remained elusive. The retrogene POU5F1B within the
      locus has a preserved open reading frame encoding a homolog of the master
      embryonic stem cell transcription factor Oct4. We find that 8q24 risk alleles are
      expression quantitative trait loci correlated with reduced expression of POU5F1B
      in prostate tissue and that predicted deleterious POU5F1B missense variants are
      also associated with risk of transformation. POU5F1 is known to be self-regulated
      by the encoded Oct4 transcription factor. We further observe that POU5F1
      expression is directly correlated with POU5F1B expression. Our results suggest
      that a pathway critical to self-renewal of embryonic stem cells may also have a
      role in the origin of cancer.

PMID- 24581740
TI  - A higher mutational burden in females supports a "female protective model" in
      neurodevelopmental disorders.
AB  - Increased male prevalence has been repeatedly reported in several
      neurodevelopmental disorders (NDs), leading to the concept of a "female
      protective model." We investigated the molecular basis of this sex-based
      difference in liability and demonstrated an excess of deleterious autosomal copy
      number variants (CNVs) in females compared to males (odds ratio [OR] = 1.46, p =
      8 * 10(-10)) in a cohort of 15,585 probands ascertained for NDs. In an
      independent autism spectrum disorder (ASD) cohort of 762 families, we found a 3
      fold increase in deleterious autosomal CNVs (p = 7 * 10(-4)) and an excess of
      private deleterious single-nucleotide variants (SNVs) in female compared to male
      probands (OR = 1.34, p = 0.03). We also showed that the deleteriousness of
      autosomal SNVs was significantly higher in female probands (p = 0.0006). A
      similar bias was observed in parents of probands ascertained for NDs. Deleterious
      CNVs (>400 kb) were maternally inherited more often (up to 64%, p = 10(-15)) than
      small CNVs < 400 kb (OR = 1.45, p = 0.0003). In the ASD cohort, increased
      maternal transmission was also observed for deleterious CNVs and SNVs. Although
      ASD females showed higher mutational burden and lower cognition, the excess
      mutational burden remained, even after adjustment for those cognitive
      differences. These results strongly suggest that females have an increased
      etiological burden unlinked to rare deleterious variants on the X chromosome.
      Carefully phenotyped and genotyped cohorts will be required for identifying the
      symptoms, which show gender-specific liability to mutational burden.

PMID- 24581741
TI  - XYLT1 mutations in Desbuquois dysplasia type 2.
AB  - Desbuquois dysplasia (DBQD) is a severe condition characterized by short stature,
      joint laxity, and advanced carpal ossification. Based on the presence of
      additional hand anomalies, we have previously distinguished DBQD type 1 and
      identified CANT1 (calcium activated nucleotidase 1) mutations as responsible for
      DBQD type 1. We report here the identification of five distinct homozygous
      xylosyltransferase 1 (XYLT1) mutations in seven DBQD type 2 subjects from six
      consanguineous families. Among the five mutations, four were expected to result
      in loss of function and a drastic reduction of XYLT1 cDNA level was demonstrated
      in two cultured individual fibroblasts. Because xylosyltransferase 1 (XT-I)
      catalyzes the very first step in proteoglycan (PG) biosynthesis, we further
      demonstrated in the two individual fibroblasts a significant reduction of
      cellular PG content. Our findings of XYLT1 mutations in DBQD type 2 further
      support a common physiological basis involving PG synthesis in the multiple
      dislocation group of disorders. This observation sheds light on the key role of
      the XT-I during the ossification process.

PMID- 24581743
TI  - Comparison of 2 proposed MLVA protocols for subtyping non-O157:H7 verotoxigenic
      Escherichia coli.
AB  - Multiple locus variable number tandem repeats (VNTRs) analysis (MLVA) has become
      a reliable tool, able to establish genetic relationships for epidemiological
      surveillance and molecular subtyping of pathogens such as verotoxigenic
      Escherichia coli (VTEC). This emerging pathogen whose primary reservoir is the
      cattle causes severe disease in humans, such as hemorrhagic colitis and hemolytic
      uremic syndrome. With the aim of comparing a recently proposed MLVA assay with
      that used routinely in our laboratory, we analyzed a set of VTEC isolates (n =
      72) obtained from meat using both assays. All samples could be typed by the new
      MLVA assay, and an increase in the number of distinct profiles (31-43) was
      observed. However, intraserotype resolution was not significantly enhanced; thus,
      the incorporation of more VNTR loci is still needed to achieve a greater
      discrimination among non-O157:H7 serotypes. 

PMID- 24581742
TI  - Loss of alpha1beta1 soluble guanylate cyclase, the major nitric oxide receptor,
      leads to moyamoya and achalasia.
AB  - Moyamoya is a cerebrovascular condition characterized by a progressive stenosis
      of the terminal part of the internal carotid arteries (ICAs) and the compensatory
      development of abnormal "moyamoya" vessels. The pathophysiological mechanisms of
      this condition, which leads to ischemic and hemorrhagic stroke, remain unknown.
      It can occur as an isolated cerebral angiopathy (so-called moyamoya disease) or
      in association with various conditions (moyamoya syndromes). Here, we describe an
      autosomal-recessive disease leading to severe moyamoya and early-onset achalasia
      in three unrelated families. This syndrome is associated in all three families
      with homozygous mutations in GUCY1A3, which encodes the alpha1 subunit of soluble
      guanylate cyclase (sGC), the major receptor for nitric oxide (NO). Platelet
      analysis showed a complete loss of the soluble alpha1beta1 guanylate cyclase and
      showed an unexpected stimulatory role of sGC within platelets. The NO-sGC-cGMP
      pathway is a major pathway controlling vascular smooth-muscle relaxation,
      vascular tone, and vascular remodeling. Our data suggest that alterations of this
      pathway might lead to an abnormal vascular-remodeling process in sensitive
      vascular areas such as ICA bifurcations. These data provide treatment options for
      affected individuals and strongly suggest that investigation of GUCY1A3 and other
      members of the NO-sGC-cGMP pathway is warranted in both isolated early-onset
      achalasia and nonsyndromic moyamoya.

PMID- 24581744
TI  - Prevalence of quinolone resistance determinants in non-typhoidal Salmonella
      isolates from human origin in Extremadura, Spain.
AB  - Resistance to the quinolones nalidixic acid (NAL) and ciprofloxacin (CIP) and the
      occurrence of quinolone resistance determinants have been investigated in 300 non
      typhoidal Salmonella from human origin, isolated in the years between 2004 and
      2008, in 6 hospitals within Extremadura (Spain). Salmonella Enteritidis was the
      major serotype found among quinolone-resistant isolates, most of which were
      clustered by clonal analysis to a single clone, which presented D87 or S83
      substitutions in GyrA. Eleven isolates presented the non-classical quinolone
      resistance phenotype (resistance to CIP and susceptibility to NAL), lacking
      mutations in the quinolone resistance determinant region of topoisomerase genes.
      Among them, one Salmonella Typhimurium isolate carried a qnrS1 gene in a low
      molecular-weight plasmid, pQnrS1-HLR25, identical to plasmids previously found in
      the UK, Taiwan, and USA. The occurrence of this genetic element could represent a
      risk for the horizontal transmission of quinolone resistance among
      Enterobacteriaceae in the Iberian Peninsula. 

PMID- 24581745
TI  - [Quality indicators in toxicological assistance].

PMID- 24581746
TI  - [Eye and systemic manifestations of Mobius syndrome].
AB  - INTRODUCTION: Mobius syndrome is characterized by damage in the nucleus of the
      sixth and seventh cranial nerves, with subsequent facial palsy and abduction
      limitation of the eyes. The aim of this article is to describe the
      ophthalmological findings of the Mobius syndrome in Mexican children. PATIENTS
      AND METHODS: A cross-sectional, retrospective, observational and descriptive
      study was conducted. A review was made of the clinical charts of patients with
      Mobius syndrome who were seen in the National Institute of Pediatrics in Mexico,
      between the years 2000 and 2010. RESULTS: A total of 64 charts were reviewed. The
      most important findings were eye abduction limitation (100%), facial palsy
      (100%), esotropia (54%), epicanthus (51.5%), entropion (22%), and history of use
      of abortion inducers in the mother in the first trimester of pregnancy (28%). We
      also found exotropia and hypertropia in some cases. CONCLUSIONS: Mobius syndrome
      has a wide spectrum of ophthalmological manifestations that are important to
      detect early in order to improve function and esthetics.

PMID- 24581748
TI  - [Hearing loss revealing sarcoidosis].

PMID- 24581747
TI  - Cytotoxic activity of hirsutanone, a diarylheptanoid isolated from Alnus
      glutinosa leaves.
AB  - BACKGROUND: The low efficacy of cancer therapy for the treatment of patients with
      advanced disease makes the development of new anticancer agents necessary.
      Because natural products are a significant source of anticancer drugs, it is
      important to explore cytotoxic activity of novel compounds from natural origin.
      PURPOSE: The aim of this work is to evaluate the cytotoxic capacity of
      hirsutanone, a diarylheptanoid isolated from Alnus glutinosa leaves. Hirsutanone
      cytotoxic way of action was also studied. MATERIAL AND METHODS: The cytotoxic
      ability of Alnus glutinosa leaves ethyl acetate extract was studied over HeLa and
      PC-3 cell lines, with the MTT colorimetric assay. Hirsutanone was isolated from
      this extract using chromatographic methods, and its structure elucidated by
      spectroscopic analysis. HT-29 cell viability after hirsutanone treatment was
      determined using SRB assay. In order to understand hirsutanone way of action,
      cytotoxicity was evaluated adding the diarylheptanoid and antioxidants. DNA
      topoisomerase II (topo II) poison activity, was also evaluated using purified
      topo II and a supercoiled form of DNA that bears specific topo II recognition and
      binding region; topo II poisons stabilize normally transient DNA-topo II cleavage
      complexes, and lead an increased yield of linear form as a consequence of a lack
      of double-strand breaks rejoining. RESULTS: The diarylheptanoid hirsutanone was
      isolated from Alnus glutinosa (L.) Gaertn. (Betulaceae) leaves extract that
      showed cytotoxic activity against PC-3 and HeLa cell lines. Hirsutanone showed
      cytotoxic activity against HT-29 human colon carcinoma cells. Pre-treatment with
      the antioxidants NAC (N-acetylcysteine) and MnTMPyP (Mn(III)tetrakis-(1-methyl-4
      pyridyl)porthyrin) reduced this activity, suggesting that reactive oxygen species
      (ROS) participate in hirsutanone-induced cancer cell death. Using human topo II
      and a DNA supercoiled form, hirsutanone was found to stabilize topo II-DNA
      cleavage complexes, acting as a topo II poison. CONCLUSION: Our data suggest
      that, like curcumin, an induction of oxidative stress and topo II-mediated DNA
      damage may play a role in hirsutanone-induced cancer cell death. Since both
      compounds share similar structure and cytotoxic profile, and curcumin is in
      clinical trials for the treatment of cancer, our results warrant further studies
      to evaluate the anticancer potential of hirsutanone.

PMID- 24581749
TI  - Left parotid mass in a 71-year-old woman.

PMID- 24581750
TI  - Response to "Sentinel lymph node biopsy versus elective neck dissection in
      patients with cT1-2N0 oral tongue squamous cell carcinoma".

PMID- 24581751
TI  - NEI's audacious goals initiative.

PMID- 24581752
TI  - A close look at pediatric eye disease.

PMID- 24581753
TI  - Ophthalmic patient data registries: defining and improving quality and outcomes.

PMID- 24581754
TI  - Peri-ictal broadband electrocorticographic activities between 1 and 700 Hz and
      seizure onset zones in 18 patients.
AB  - OBJECTIVE: We investigated the relationship between locations of broadband peri
      ictal electrocorticographic activities determined by a semi-automatic detection
      method and seizure onset zones in medically intractable epilepsy patients.
      METHODS: We included 18 patients. Peri-ictal periods (-15 to +5s from the ictal
      onset) were divided into 4 periods of 5s duration each in bandwidth from 1 to 700
      Hz divided into 11 bins. Thereafter, we calculated the mean overlapping
      percentage of the maximum amplitude activity electrodes with the seizure onset
      zone in the total number of seizures in each patient. Significance was considered
      at an adjusted p-value of 0.05. RESULTS: By the maximum amplitude method with the
      Bonferroni correction, only high-frequency activities (>60 Hz) during -5 to 0 s
      from the ictal onset were significantly related to seizure onset zones. In post
      hoc analyses, bands in 60-139 Hz and 4-7 Hz were significantly related to seizure
      onset zones in the Bonferroni correction. However, after the less conservative
      Benjamini-Yekutieli correction and with the epileptogenicity index, other bands
      and periods after -10s from the ictal onset were also related with seizure onset
      zones. SIGNIFICANCE: Detailed bands, timings and analytic methods of peri-ictal
      activities with high relationships to seizure onset zones were identified.

PMID- 24581756
TI  - The questionable benefits of exchanging saturated fat with polyunsaturated fat.

PMID- 24581755
TI  - Can influenza vaccination coverage among healthcare workers influence the risk of
      nosocomial influenza-like illness in hospitalized patients?
AB  - BACKGROUND: Approximately 20% of healthcare workers are infected with influenza
      each year, causing nosocomial outbreaks and staff shortages. Despite influenza
      vaccination of healthcare workers representing the most effective preventive
      strategy, coverage remains low. AIM: To analyse the risk of nosocomial influenza
      like illness (NILI) among patients admitted to an acute care hospital in relation
      to influenza vaccination coverage among healthcare workers. METHODS: Data
      collected over seven consecutive influenza seasons (2005-2012) in an Italian
      acute care hospital were analysed retrospectively. Three different sources of
      data were used: hospital discharge records; influenza vaccination coverage among
      healthcare workers; and incidence of ILI in the general population. Clinical
      modification codes from the International Classification of Diseases, 9(th)
      Revision were used to define NILI. FINDINGS: Overall, 62,343 hospitalized
      patients were included in the study, 185 (0.03%) of whom were identified as NILI
      cases. Over the study period, influenza vaccination coverage among healthcare
      workers decreased from 13.2% to 3.1% (P < 0.001), whereas the frequency of NILI
      in hospitalized patients increased from 1.10/00 to 5.70/00 (P < 0.001). A
      significant inverse association was observed between influenza vaccination
      coverage among healthcare workers and rate of NILI among patients (adjusted odds
      ratio 0.97, 95% confidence interval 0.94-0.99). CONCLUSION: Increasing influenza
      vaccination coverage among healthcare workers could reduce the risk of NILI in
      patients hospitalized in acute hospitals. This study offers a reliable and cost
      saving methodology that could help hospital management to assess and make known
      the benefits of influenza vaccination among healthcare workers.

PMID- 24581757
TI  - Prognostic factors and outcomes of adults with hemophagocytic
      lymphohistiocytosis.
AB  - OBJECTIVE: To describe the prognostic factors and outcomes of adults with
      hemophagocytic lymphohistiocytosis (HLH), a rare disorder caused by pathologic
      activation of the immune system. PATIENTS AND METHODS: The study population
      consisted of a consecutive cohort of adult (age >=18 years) patients treated at
      Mayo Clinic in Rochester, Minnesota, from January 1, 1996, through December 31,
      2011, in whom a diagnosis of HLH was suspected and subsequently confirmed by
      retrospective review using the HLH-04 diagnostic criteria. RESULTS: Of 250 adult
      patients suspected of having HLH, 62 met the HLH-04 diagnostic criteria and were
      included in the final analysis. The median age was 49 years (range, 18-87 years),
      and 42 (68%) were male. The underlying cause of HLH was malignant tumor in 32
      patients (52%), infection in 21 patients (34%), autoimmune disorder in 5 patients
      (8%), and idiopathic disease in 4 patients (6%). After a median follow-up of 42
      months, 41 patients (66%) had died. The median overall survival of the entire
      cohort was 2.1 months. The median overall survival of patients with tumor
      associated HLH was 1.4 months compared with 22.8 months for patients with non
      tumor-associated HLH (P=.01). The presence of a malignant tumor and
      hypoalbuminemia were significant predictors of inferior survival on multivariate
      analysis. CONCLUSION: In this large series of adults with secondary HLH treated
      at a single tertiary care center, patients with low serum albumin levels and
      tumor-associated HLH had a markedly worse survival. Hemophagocytic
      lymphohistiocytosis remains elusive and challenging to clinicians who must
      maintain a high index of suspicion. The recent discovery of several novel
      diagnostic and therapeutic modalities may improve outcomes of adult patients with
      HLH.

PMID- 24581758
TI  - Personalized medicine for breast cancer: it is a new day!
AB  - Breast cancer remains the most common cancer diagnosed in women in the United
      States and is second only to lung cancer as a cause of cancer mortality. Breast
      cancer has become the prototypical solid tumor where targets have been identified
      within the tumor allowing for a personalized approach of systemic therapy. 

PMID- 24581759
TI  - Should atypia of undetermined significance be subclassified to better estimate
      risk of thyroid cancer?
AB  - BACKGROUND: Atypia or follicular lesion of undetermined significance (AUS) is a
      cytologic category of thyroid aspirates with a wide range of reported malignancy.
      We aimed to determine whether specific cytologic features are associated with
      different rates of thyroid malignancy. METHODS: All thyroid fine needle
      aspiration biopsies with AUS from 2010 to 2012 were reanalyzed. Cytologic
      features were correlated with final pathology. Cytopathologists were blinded to
      the original cytologic interpretation and final diagnosis. RESULTS: Seventy-six
      patients had AUS; 39 (54%) underwent surgery with a malignancy rate of 18%.
      Specimens with moderate or large amount of thin colloid and absent or few nuclear
      inclusions had a >88% rate of benign disease. More than rare nuclear inclusions
      or grooves were associated with a higher rate of cancer (75% vs 9%, P = .005; 45%
      vs 7%, P = .003). CONCLUSIONS: Patients with AUS and more than rare nuclear
      inclusions or grooves are at higher risk for cancer and should forego repeat fine
      needle aspiration biopsy and undergo thyroidectomy.

PMID- 24581760
TI  - Repeal of the Michigan helmet law: early clinical impacts.
AB  - BACKGROUND: Michigan repealed a 35-year mandatory helmet law on April 13, 2012.
      We examined the early clinical impacts at a level 1 trauma center in West
      Michigan. METHODS: Retrospective cohort study comparing outcomes among motorcycle
      crash victims in a 7-month period before and after the helmet law repeal.
      RESULTS: One hundred ninety-two patients were included. After the repeal,
      nonhelmeted motorcyclists rose from 7% to 29% (P < .01). There was no difference
      in mortality rate after admission; however, crash scene fatalities increased
      significantly. Intensive care unit length of stay, mechanical ventilation time,
      and cost of stay were also higher in the nonhelmeted cohort (P < .05).
      CONCLUSIONS: Our study highlights the negative ramifications of repealing a
      mandatory helmet law. Motorcyclists not wearing helmets increased significantly
      in a short period of time. Nonhelmeted motorcyclists more frequently died on the
      scene, spent more time in the intensive care unit, required longer ventilator
      support, and had higher medical costs.

PMID- 24581761
TI  - Long-term efficacy of laparoscopic cholecystectomy for the treatment of biliary
      dyskinesia.
AB  - BACKGROUND: Laparoscopic cholecystectomy is the treatment of choice for biliary
      dyskinesia; however, long-term outcomes remain unclear. METHODS: A retrospective
      review of patients diagnosed with biliary dyskinesia and treated with
      laparoscopic cholecystectomy at a single institution between 2001 and 2012 was
      conducted. Long-term outcome data were obtained by telephonic interview using a
      modified Likert scale. RESULTS: Sixty-seven patients met inclusion criteria, of
      which 34 patients (51%) had long-term follow-up data. Mean time of follow-up was
      65 (range: 6 to 134) months. Long-term follow-up demonstrated symptom response in
      88% (n = 30) of patients (responders), compared to no response in 12% (n = 4) of
      patients (nonresponders). Responders underwent a mean of 1.56 preoperative
      diagnostic procedures, compared to 2.5 for nonresponders (P = .01). CONCLUSION:
      This represents the longest mean time of follow-up study demonstrating the
      success of laparoscopic cholecystectomy to improve symptoms in patients with
      biliary dyskinesia.

PMID- 24581762
TI  - Esophagectomy outcomes at a mid-volume cancer center utilizing prospective
      multidisciplinary care and a 2-surgeon team approach.
AB  - BACKGROUND: Esophagectomy is associated with high morbidity and mortality,
      leading to calls for restricted performance at high-volume centers. METHODS:
      Patients with esophageal cancer were evaluated prospectively in a
      multidisciplinary tumor board from January 2012 - December 2012. A 2-surgeon team
      was utilized and detailed outcomes were assessed prospectively. RESULTS: Thirty
      one patients underwent esophagectomy, 20 patients underwent laparoscopic
      transhiatal (65%) approach, and 11 patients underwent laparoscopically assisted
      Ivor-Lewis (35%) approach. Eighty-one percent of the patients were male, with a
      median age of 64 years (range: 35 to 83 years) and 73% of the patients had
      adenocarcinoma. Neoadjuvant chemoradiation was performed in 79% of the patients.
      R0 resection was achieved in 29 (94%) patients, median nodes identified were 15.
      Major complications (grade III to V) occurred in 13 (42%) patients and did not
      correlate with surgical techniques, anastomotic leak occurred in 5 (16%)
      patients, and significant pulmonary complications occurred in 11 (35%) patients.
      The length of stay at the hospital was 10 days, readmission rate 23%, and 30-day
      mortality rate 6%. CONCLUSIONS: High-quality esophagectomy can be performed
      safely at a mid-volume cancer center. Our outcomes question the reliance on
      volume alone as an indicator of cancer surgical quality.

PMID- 24581763
TI  - Obesity in trauma: outcomes and disposition trends.
AB  - BACKGROUND: Obesity's effect on the outcomes of trauma patients remains
      inconclusive. METHODS: A retrospective review of all falls, motor vehicle
      collisions (MVCs), and penetrating trauma patients admitted from January 2008 to
      December 2012 was performed. The outcomes evaluated included mortality, length of
      stay at hospital, and discharge disposition. Patients were grouped according to
      the body mass index (BMI) and stratified by injury severity scores. RESULTS: Two
      thousand one hundred ninety six patients were analyzed; 132 penetrating, 913
      falls, and 1,151 MVCs. Penetrating traumas had no significant difference in
      outcomes. In falls, obese patients had a lower mortality (P = .035). In MVCs,
      obese patients had longer hospitalizations (P = .02), and mild and moderate MVC
      injuries were less likely to be discharged home (P = .032 and .003). Obese
      patients sustained fewer head injuries in falls and MVCs (P = .005 and .043,
      respectively). CONCLUSIONS: In falls, a higher BMI may benefit patients. However,
      an increasing BMI is associated with a longer length of stay at hospital, and
      decreased likelihood of discharge to home.

PMID- 24581764
TI  - Surgical, oncologic, and cosmetic differences between oncoplastic and
      nononcoplastic breast conserving surgery in breast cancer patients.
AB  - BACKGROUND: There is a lack of information regarding the safety, complication
      rate, and cosmetic outcome of oncoplastic breast conserving surgery. The purpose
      of this study is to evaluate and compare oncoplastic and nononcoplastic
      procedures. METHODS: A retrospective review was conducted of patients treated
      with oncoplastic or nononcoplastic lumpectomies. Immediate and long-term
      complication rates and cosmetic satisfaction were compared. RESULTS: Of the 142
      surgeries, 58 were oncoplastic lumpectomies (40.8%). Oncoplastic patients were
      younger than nononcoplastic patients (60.9 vs 65.2 years, P = .043). Immediate
      complications were similar with the exception of nonhealing wounds (oncoplastic =
      8.6% vs nononcoplastic = 1.2%, P = .042). Cosmetic complaints were similar, but
      fat necrosis was more common in the oncoplastic group (25.9% vs 9.5%, P = .009).
      Time to radiation and number of future biopsies were similar between the groups.
      CONCLUSION: Oncoplastic lumpectomy is a safe alternative to standard lumpectomy
      for selected breast cancer patients.

PMID- 24581765
TI  - The effect of timing of postmastectomy radiation on implant-based breast
      reconstruction: a retrospective comparison of complication outcomes.
AB  - BACKGROUND: The optimal timing of postmastectomy radiation for women undergoing
      delayed permanent implant exchange continues to remain controversial. The
      objective of our study is to compare complication rates when tissue expanders are
      exchanged for permanent implants pre- vs postradiation. METHODS: A retrospective
      review of 54 consecutive patients who underwent implant-based breast
      reconstruction and received postmastectomy radiation was conducted. Complications
      including infection, implant loss, and capsular contracture (measured in Baker
      score) were compared between the 2 groups. RESULTS: Of the patients studied, 32
      patients had radiation before placement of permanent implants, whereas 22
      patients received radiation after implant placement. There was no difference in
      individual complication rates between the 2 groups. CONCLUSIONS: In our study of
      54 patients, the timing of radiation did not affect individual complication rates
      for patients who underwent implant-based breast reconstruction after immediate
      tissue expander placement.

PMID- 24581766
TI  - Pediatric melanoma in New Mexico American Indians, Hispanics, and non-Hispanic
      whites, 1981-2009.
AB  - BACKGROUND: Pediatric melanoma rates are increasing nationally. Our purpose was
      to determine the incidence of melanoma in New Mexico's (NM's) American Indian,
      Hispanic, and non-Hispanic white children. METHODS: A retrospective review (1981
      to 2009) of the NM Tumor Registry was conducted. Melanomas diagnosed in children
      <19 years of age were identified. Average annual age-adjusted incidence rates per
      million were calculated. RESULTS: Sixty-four cases were identified. Rates per
      million were 7.4 for non-Hispanic whites, 2.1 for Hispanics, and 3.3 for American
      Indians. Fifty-nine percent were women. Fifty-five (86%) cases were localized, 6
      (9%) were regional, and 1 (3%) case was metastatic. Majority of cases (49/64;
      77%) occurred in children >14 years of age. American Indians presented with
      thicker melanomas as compared to whites and Hispanics. CONCLUSIONS: Incidence
      rates for pediatric melanoma in NM are highest for non-Hispanic whites. Distant
      metastasis is uncommon. Melanoma in children is rare, but practitioners must be
      aware of its occurrence for prompt diagnosis and treatment.

PMID- 24581767
TI  - Preliminary results of Zenith Fenestrated abdominal aortic aneurysm endovascular
      grafts.
AB  - BACKGROUND: Patients with juxtarenal aortic aneurysms who are unfit for open
      repair may be considered for fenestrated endovascular repair (fenEVAR). We report
      our initial experience with fenEVAR. METHODS: We reviewed the data on all our
      patients receiving fenEVAR for juxtarenal aortic aneurysms. RESULTS: Eight
      patients, average age 75 years, underwent fenEVAR. Endografts were designed from
      details obtained from preoperative computed tomography angiography. There were 6
      grafts with superior mesenteric scallops and bilateral renal fenestrations, 1
      with bilateral renal scallops, and 1 with a single renal fenestration. All
      patients survived 30 days. There was no renal failure requiring dialysis. At 10
      weeks, 1 patient died from acute intestinal ischemia and multisystem organ
      failure, and another died from respiratory failure. CONCLUSIONS: It is feasible
      to offer fenEVAR to patients who are poor candidates for open repair. However,
      these procedures are technically challenging. Early outcomes are less favorable
      than other aortic endovascular procedures.

PMID- 24581768
TI  - Incremental cost of complications in colectomy: a warranty guided approach to
      surgical quality improvement.
AB  - BACKGROUND: We assessed the warranty cost for colectomy at a single institution,
      as defined by the additional cost of treating complications distributed across
      all patients treated. METHODS: All segmental colectomies from July 8 to June 12
      were reviewed for 0, 1, 2, and >=3 complications. Warranty cost is defined as
      follows: ([mean additional cost of the case with complication(s) - mean base case
      cost] * number of episodes)/total population. RESULTS: Thousand four hundred
      twenty-two colectomies were analyzed. The lowest cost case was a laparoscopic
      resection with 0 complications ($7,739 +/- 4,150). Warranty costs were less for
      laparoscopic versus open colectomy (0 - $0, 1 - $128, 2 - $66, >=3 - $248 vs 0 -
      $1,036, 1 - $501, 2 - $520, >=3 - $1,971). This was true for costs associated
      with readmission ($303 vs $1,519). Emergency status and elderly status also
      impacted warranty costs. CONCLUSIONS: The data demonstrate that warranty costs
      were highest with open colectomy, emergency cases, and the elderly. These data
      can be used to measure both quality and cost impact of mitigation strategies.

PMID- 24581769
TI  - Can ultrasound common bile duct diameter predict common bile duct stones in the
      setting of acute cholecystitis?
AB  - BACKGROUND: Our aim is assessment of ultrasound (US) common bile duct (CBD)
      diameter to predict the presence of CBD stones in acute cholecystitis (AC).
      METHODS: A retrospective review from 2007 to 2011 with codes for ultrasound,
      magnetic resonance cholangiopancreatography (MRCP), endoscopic retrograde
      cholangiopancreatography, and AC was conducted. RESULTS: The incidence of CBD
      stones was 1.8%. Two hundred forty eight individuals had US+MRCP+ERCP+AC, of
      which 48 had CBD stones and 200 did not have CBD stones. US CBD diameter range
      was 3.6 to 19 mm. Ninety percent of MRCPs were negative, and it delayed care by
      2.9 days. Mean CBD diameter was narrower in those negative for CBD stones (5.8 vs
      7.08; P = .0043). Groups based on diameter ranges <6, 6 to 9.9, and >=10 mm
      demonstrated 14%, 14%, and 39% CBD stones, respectively. CONCLUSIONS: US CBD
      diameter is not sufficient to identify patients at significant risk for CBD
      stones. MRCP delayed care by 2.9 days. Intraoperative cholangiography may be more
      effective, based on the low risk of CBD stones in AC.

PMID- 24581770
TI  - Laser vision correction among physicians: "the proof of the pudding is in the
      eating".

PMID- 24581771
TI  - Artificial iris devices: benefits, limitations, and management of complications.
AB  - PURPOSE: To discuss limitations and benefits of a custom-made foldable artificial
      iris (Artificialiris) in the management of acquired iris defects. SETTING:
      Hochkreuzklinik Eye Hospital, Bonn, and the Department of Ophthalmology,
      University of Cologne, Germany. DESIGN: Case series. METHODS: We reviewed the
      clinical course and surgical management in eyes with sight-compromising
      complications after phakic anterior chamber implantation of synthetic iris
      devices between November 2011 and January 2012. RESULTS: Three eyes of 2 patients
      were reviewed. One patient developed cataract and corneal decompensation after
      anterior chamber artificial iris implantation in the left eye to treat post
      uveitic mydriasis. Further treatment included artificial iris removal, cataract
      surgery, iridoplasty, and Descemet membrane endothelial keratoplasty (DMEK). By
      the 6-month follow-up, visual acuity had increased from 20/50 to 20/25. The
      second patient presented with bilateral secondary glaucoma, cataract, corneal
      edema, and iris atrophy after implantation of Newiris devices for cosmetic
      reasons. He consecutively had binocular explantation of the cosmetic devices,
      cataract surgery, artificial iris implantation, and DMEK in both eyes and Ahmed
      valve implantation in the right eye. During the 6-month follow-up, the
      intraocular pressure remained sufficiently adjusted in both eyes. Photophobia was
      eliminated, and visual acuity improved to 20/32 in the right eye and 20/20 in the
      left eye. CONCLUSIONS: In patients with major iris defects ineligible for
      pupilloplasties, the artificial iris allows functionally and esthetically
      satisfactory anterior segment reconstruction. To prevent secondary complications,
      the artificial iris should only be implanted in aphakic or pseudophakic eyes and
      placed in the posterior chamber.

PMID- 24581772
TI  - Long-term follow-up after laser vision correction in physicians: quality of life
      and patient satisfaction.
AB  - PURPOSE: To evaluate the satisfaction and quality of life after laser vision
      correction (LVC) exclusively in a physician population. SETTING: Cole Eye
      Institute, Cleveland Clinic, Cleveland, Ohio, USA. DESIGN: Cohort study. METHODS:
      A 12-question survey targeted toward physicians and the unique qualities of their
      experience with refractive surgery was sent to physicians who had refractive
      surgery at the Cole Eye Institute between 2000 and 2012. In conjunction, the
      visual outcomes and clinical information of physicians who received the survey
      were reviewed. RESULTS: Two hundred twenty-six physicians (439 eyes) met the
      inclusion criteria for our study. One hundred thirty-two physicians (58%)
      responded to the survey and reported an overall satisfaction rate of 95.3%.
      Respondents included surgeons (28.0%), physicians who perform procedures but not
      surgery (43.2%), and physicians who do not perform procedures or surgery (28.8%).
      Of the physicians, 84.8% reported an improvement in the quality of vision
      compared with the corrected preoperative vision, 39.0% reported that their
      ability to perform procedures accurately had improved and 1.6% said they believed
      their ability to perform procedures was less. Ninety-six percent reported they
      would have the procedure again. Visual outcomes showed high levels of surgical
      predictability, efficacy, and safety. CONCLUSION: Despite high visual demands,
      physicians having LVC had a high percentage of good visual outcomes,
      satisfaction, and quality-of-life improvements.

PMID- 24581773
TI  - Comparison of 2 wavefront-guided excimer lasers for myopic laser in situ
      keratomileusis: one-year results.
AB  - PURPOSE: To compare laser in situ keratomileusis (LASIK) outcomes between 2
      wavefront-guided excimer laser systems in the treatment of myopia. SETTING:
      University eye clinic, Palo Alto, California, USA. DESIGN: Prospective
      comparative case series. METHODS: One eye of patients was treated with the
      Allegretto Wave Eye-Q system (small-spot scanning laser) and the fellow eye with
      the Visx Star Customvue S4 IR system (variable-spot scanning laser). Evaluations
      included measurement of uncorrected visual acuity, corrected visual acuity, and
      wavefront aberrometry. RESULTS: One hundred eyes (50 patients) were treated. The
      mean preoperative spherical equivalent (SE) refraction was -3.89 diopters (D) +/-
      1.67 (SD) and -4.18 +/- 1.73 D in the small-spot scanning laser group and
      variable-spot scanning laser group, respectively. There were no significant
      differences in preoperative higher-order aberrations (HOAs) between the groups.
      Twelve months postoperatively, all eyes in the small-spot scanning laser group
      and 92% in the variable-spot scanning laser group were within +/-0.50 D of the
      intended correction (P = .04). At that time, the small-spot scanning laser group
      had significantly less spherical aberration (0.12 versus 0.15) (P = .04) and
      significantly less mean total higher-order root mean square (0.33 MUm versus 0.40
      MUm) (P = .01). Subjectively, patients reported that the clarity of night and day
      vision was significantly better in the eye treated with the small-spot scanning
      laser. CONCLUSIONS: The predictability and self-reported clarity of vision of
      wavefront-guided LASIK were better with the small-spot scanning laser. Eyes
      treated with the small-spot scanning laser had significantly fewer HOAs.

PMID- 24581774
TI  - Reproducibility of manifest refraction between surgeons and optometrists in a
      clinical refractive surgery practice.
AB  - PURPOSE: To measure and compare the interobserver reproducibility of manifest
      refraction according to a standardized protocol for normal preoperative patients
      in a refractive surgery practice. SETTING: Private clinic, London, United
      Kingdom. DESIGN: Retrospective case series. METHODS: This retrospective study
      comprised patients attending 2 preoperative refractions before laser vision
      correction. The first manifest refraction was performed by 1 of 7 optometrists
      and the second manifest refraction by 1 of 2 surgeons, all trained using a
      standard manifest refraction protocol. Spherocylindrical data were converted into
      power vectors for analysis. The dioptric power differences between observers were
      calculated and analyzed. RESULTS: One thousand nine hundred twenty-two
      consecutive eyes were stratified into a myopia group and a hyperopia group and
      then further stratified by each surgeon-optometrist combination. The mean surgeon
      optometrist dioptric power difference was 0.21 diopter (D) (range 0.15 to 0.32
      D). The mean difference in spherical equivalent refraction was 0.03 D, with 95%
      of all refractions within +/-0.44 D for all optometrist-surgeon combinations. The
      severity of myopic or hyperopic ametropia did not affect the interobserver
      reproducibility of the manifest refraction. CONCLUSIONS: There was close
      agreement in refraction between surgeons and optometrists using a standard
      manifest refraction protocol of less than 0.25 D. This degree of interobserver
      repeatability is similar to that in intraobserver repeatability studies published
      to date and may represent the value of training and the use of a standard
      manifest refraction protocol between refraction observers in a refractive surgery
      practice involving co-management between surgeons and optometrists.

PMID- 24581775
TI  - Sealability of ultrashort-pulse laser and manually generated full-thickness clear
      corneal incisions.
AB  - PURPOSE: To compare the sealability and geometry of full-thickness clear corneal
      incisions (CCIs) created manually or with an ultrashort-pulse laser. SETTING:
      Lensar, Inc., Orlando, Florida, USA. DESIGN: Experimental study. METHODS: Ex vivo
      human donor globes were randomly assigned to groups for the manual or laser
      generated full-thickness CCIs. Standard 3-plane manual or laser incisions were
      made in 22 globes. Incision geometry was measured using an optical coherence
      tomographer. Sealability was assessed by inflating globes to physiologic
      intraocular pressure (IOP) and pressing a mechanical plunger into the globe to
      deform the globe and increase IOP until leakage was detected using the Seidel
      test. The test of sealability at lowered IOP was performed similarly; the
      anterior chamber was monitored for signs of ingress of a povidone-iodine 10%
      solution placed externally. RESULTS: The mean IOP elevation at which leakage
      occurred was higher for the laser than for manually generated full-thickness
      CCIs, indicating that the mean sealability was better for the laser. However, t
      tests showed that there was no statistically significant difference in the mean
      IOP elevation at which full-thickness incision leakage occurred between manual
      and laser full-thickness CCIs. Thus, the sealability of the manual and laser full
      thickness CCIs were equivalent for the incision geometry tested. The laser full
      thickness CCIs were statistically closer to target geometry and showed less
      variability than the manual full-thickness CCIs. CONCLUSIONS: The sealability of
      laser and manual full-thickness CCIs were statistically equivalent. The laser
      full-thickness CCIs were more consistent in geometry and closer to the target
      incision geometry.

PMID- 24581776
TI  - Refractive Surgical Question: March consultation #1.

PMID- 24581777
TI  - March consultation #2.

PMID- 24581778
TI  - March consultation #4.

PMID- 24581779
TI  - March consultation #3.

PMID- 24581780
TI  - March consultation #5.

PMID- 24581781
TI  - March consultation #7.

PMID- 24581782
TI  - March consultation #6.

PMID- 24581783
TI  - March consultation #8.

PMID- 24581784
TI  - Reply: To PMID 23830559.

PMID- 24581785
TI  - Mitomycin-C in photorefractive keratectomy.

PMID- 24581786
TI  - Reply: To PMID 24054967.

PMID- 24581787
TI  - Intracameral moxifloxacin injection to prevent endophthalmitis.

PMID- 24581788
TI  - Practical differences between 3 femtosecond phaco laser platforms.

PMID- 24581789
TI  - Reply: To PMID 24160384.

PMID- 24581790
TI  - Vital dye and characteristics of the lens capsule.

PMID- 24581791
TI  - Lean versus obese diabetes mellitus patients in the United States minority
      population.
AB  - OBJECTIVE: To identify special characteristics in large group of lean diabetes
      minority patients in comparison to obese type 2 diabetes. METHODS: 1784 Lean (BMI
      <25) diabetes patients were identified and compared with 8630 obese (BMI >=30)
      patients. Patients with Type 1 Diabetes (N=523) were excluded. Patient data,
      including demographics, psychosocial factors, insulin use, and complications was
      analyzed. RESULTS: In lean compared to obese, there was male predominance (62% vs
      48%, p<0.001), higher prevalence of insulin use (49% vs 44%, p=0.001), lower
      TG/HDL (2.28 vs 3.4, p<0.001), and higher prevalence of alcoholism (5.7% vs 2.4%,
      p<0.001) and pancreatitis (3.6% vs 0.9%, p<0.001). In both groups, African
      Americans and Latinos were the prevalent ethnicities (38%, 34% vs. 53%,31%). When
      comparing patients within the lean group who were on insulin (49%) to those on
      oral medications, there were more males (65% vs. 59%, p<0.001), earlier age of
      onset (40+/-14 vs. 47+/-12, p<0.001), lower BMI (22.1+/-2 vs. 22.6+/-1.7,
      p<0.001) and lower TG/HDL (2.18 vs. 2.42, p=0.021). CONCLUSIONS: A subset of
      diabetes patients in the United States minority population are lean and may have
      rapid beta cell failure. The etiology is not clear and acquired factors,
      genetics, and autoimmunity may be contributory.

PMID- 24581792
TI  - The need for schools in Afghanistan to be declared as zones of peace and
      neutrality. NGOs and communities can work together to promote humane schools.

PMID- 24581793
TI  - Call for Research on Women on behalf of Women Stroke Association.

PMID- 24581794
TI  - Self-reported adolescent behavioral adjustment: effects of prenatal cocaine
      exposure.
AB  - PURPOSE: To assess the direct effects of prenatal cocaine exposure (PCE) on
      adolescent internalizing, externalizing, and attention problems, controlling for
      confounding drug and environmental factors. METHOD: At 12 and 15 years of age,
      371 adolescents (189 PCE and 182 noncocaine exposed), primarily African-American
      and of low socioeconomic status, participating in a longitudinal, prospective
      study from birth were assessed for behavioral adjustment using the Youth Self
      Report. RESULTS: Longitudinal mixed model analyses indicated that PCE was
      associated with greater externalizing behavioral problems at ages 12 and 15 years
      and more attention problems at age 15, after controlling for confounders. PCE
      effects were not found for internalizing behaviors. PCE adolescents in
      adoptive/foster care reported more externalizing and attention problems than PCE
      adolescents in biological mother/relative care at age 12 or noncocaine-exposed
      adolescents at both ages. No PCE by gender interaction was found. Prenatal
      marijuana exposure, home environment, parental attachment and monitoring, family
      conflict, and violence exposure were also significant predictors of adolescent
      behavioral adjustment. CONCLUSIONS: PCE is a risk factor for poor behavioral
      adjustment in adolescence.

PMID- 24581795
TI  - Opioid use among adolescent patients treated for headache.
AB  - PURPOSE: To determine the pervasiveness of opioid prescribing for adolescents
      with headache and patient and provider characteristics associated with likelihood
      of opioid prescribing. METHODS: This observational cohort analysis used
      commercial medical and pharmacy claims between January 1, 2007 and December 31,
      2008. Included were adolescents (13-17 years of age) with newly diagnosed
      headache, >=2 distinct claims for headache, and >=12 months health plan
      eligibility preindex and postindex. Adolescents with a trauma diagnosis at any
      point were excluded. The primary outcome was current practice patterns, measured
      by a number of opioid claims, a percentage of patients prescribed opioids, a
      number of opioid prescriptions per year, a length of opioid therapy, and a
      frequency of specific comorbidities. A secondary outcome characterized providers
      and practice settings, comparing patients who received opioids with those who did
      not. RESULTS AND CONCLUSIONS: Of 8,373 adolescents with headache, 46% (3,859
      patients) received an opioid prescription. Nearly half (48%) received one opioid
      prescription during follow-up; 29% received >=3 opioid prescriptions. Of those
      with opioid prescriptions, 25% (977 patients) had a migraine diagnosis at index
      date. Among adolescents who received opioids, 28% (1,076 adolescents) had an
      emergency department (ED) visit for headache during follow-up versus 14% (608
      adolescents) who did not receive opioids (p < .01). ED visits with a headache
      diagnosis during follow-up were strongly correlated with opioid use after
      adjusting for other covariates (odds ratio, 2.02; 95% confidence interval, 1.79
      2.29). Despite the treatment guidelines recommending against their use, a large
      proportion of adolescents with headache were prescribed opioids. ED visits were
      strongly correlated with opioid prescriptions.

PMID- 24581796
TI  - [Lung cancer in the elderly: what about surgery?].
AB  - Geriatric oncology is a rapidly expanding domain because of the deep
      epidemiological changes of the last decades related to the ageing of the
      population. Lung cancer treatment in patients 75 years and over is a major issue
      of thoracic oncology. Curative surgery remains the treatment offering the best
      survival rates to the patient whatever his age. The important variability
      observed within the elderly forces us to take into account their specificities,
      in particular for ageing physiology and associated comorbidities. Thus,
      preoperative workup permitting to assess the resectability of the tumor but also
      the operability of the patient is all the more essential in the advanced age that
      it must be adapted to the particular characteristics of the elderly. Thanks to
      recent data of the literature, morbidity and mortality associated to surgical
      treatment are now better characterized and considered as acceptable in accordance
      with long-term survival. Clinical investigation remains essential to acquire a
      better knowledge of potential benefit of multimodal treatments in the elderly,
      for which very few data are available.

PMID- 24581797
TI  - A comparison of muscle energy models for simulating human walking in three
      dimensions.
AB  - The popular Hill model for muscle activation and contractile dynamics has been
      extended with several different formulations for predicting the metabolic energy
      expenditure of human muscle actions. These extended models differ considerably in
      their approach to computing energy expenditure, particularly in their treatment
      of active lengthening and eccentric work, but their predictive abilities have
      never been compared. In this study, we compared the predictions of five different
      Hill-based muscle energy models in 3D forward dynamics simulations of normal
      human walking. In a data-tracking simulation that minimized muscle fatigue, the
      energy models predicted metabolic costs that varied over a three-fold range (2.45
      7.15 J/m/kg), with the distinction arising from whether or not eccentric work was
      subtracted from the net heat rate in the calculation of the muscle metabolic
      rate. In predictive simulations that optimized neuromuscular control to minimize
      the metabolic cost, all five models predicted similar speeds, step lengths, and
      stance phase durations. However, some of the models predicted a hip circumduction
      strategy to minimize metabolic cost, while others did not, and the accuracy of
      the predicted knee and ankle angles and ground reaction forces also depended on
      the energy model used. The results highlights the need to clarify how eccentric
      work should be treated when calculating muscle energy expenditure, the difficulty
      in predicting realistic metabolic costs in simulated walking even with a detailed
      3D musculoskeletal model, the potential for using such models to predict
      energetically-optimal gait modifications, and the room for improvement in
      existing muscle energy models and locomotion simulation frameworks.

PMID- 24581798
TI  - A noninvasive approach to determine viscoelastic properties of an individual
      adherent cell under fluid flow.
AB  - Mechanical properties of cells play an important role in their interaction with
      the extracellular matrix as well as the mechanotransduction process. Several in
      vitro techniques have been developed to determine the mechanical properties of
      cells, but none of them can measure the viscoelastic properties of an individual
      adherent cell in fluid flow non-invasively. In this study, techniques of fluid
      structure interaction (FSI) finite element method and quasi-3-dimensional (quasi
      3D) cell microscopy were innovatively applied to the frequently used flow chamber
      experiment, where an adherent cell was subjected to fluid flow. A new non
      invasive approach, with cells at close to physiological conditions, was
      established to determine the viscoelastic properties of individual cells. The
      results showed an instantaneous modulus of osteocytes of 0.49 +/- 0.11 kPa, an
      equilibrium modulus of 0.31 +/- 0.044 kPa, and an apparent viscosity coefficient
      of 4.07 +/- 1.23 kPas. This new quantitative approach not only provides an
      excellent means to measure cell mechanical properties, but also may help to
      elucidate the mechanotransduction mechanisms for a variety of cells under fluid
      flow stimulation.

PMID- 24581799
TI  - Non-destructive assessment of human ribs mechanical properties using quantitative
      ultrasound.
AB  - Advanced finite element models of the thorax have been developed to study, for
      example, the effects of car crashes. While there is a need for material
      properties to parameterize such models, specific properties are largely missing.
      Non-destructive techniques applicable in vivo would, therefore, be of interest to
      support further development of thorax models. The only non-destructive technique
      available today to derive rib bone properties would be based on quantitative
      computed tomography that measures bone mineral density. However, this approach is
      limited by the radiation dose. Bidirectional ultrasound axial transmission was
      developed on long bones ex vivo and used to assess in vivo health status of the
      radius. However, it is currently unknown if the ribs are good candidates for such
      a measurement. Therefore, the goal of this study is to evaluate the relationship
      between ex vivo ultrasonic measurements (axial transmission) and the mechanical
      properties of human ribs to determine if the mechanical properties of the ribs
      can be quantified non-destructively. The results show statistically significant
      relationships between the ultrasonic measurements and mechanical properties of
      the ribs. These results are promising with respect to a non-destructive and non
      ionizing assessment of rib mechanical properties. This ex vivo study is a first
      step toward in vivo studies to derive subject-specific rib properties. 

PMID- 24581800
TI  - Study of the residues involved in the binding of beta1 to beta3 subunits in the
      sodium channel.
AB  - The voltage-gated sodium channel (VGSC) is a complex, which is composed of one
      pore-forming alpha subunit and at least one beta subunit. Up to now, five beta
      subunits are known: beta1/beta1A, beta1B, beta2, beta3, and beta4, encoded by
      four genes (SCN1B~SCN4B). It is critical to have a deep understanding of the
      interaction between beta1 and beta3 subunits, two subunits which frequently
      appear in many diseases concurrently. In this study, we had screened out the new
      template of beta1 subunit for homology modelling, which shares higher similarity
      to beta3. Docking studies of the beta1 and beta3 homology model were conducted,
      and likely beta1 and beta3 binding loci were investigated. The results revealed
      that beta1-beta3 is more likely to form a di-polymer than beta1-beta1 based on
      molecular interaction analysis, including potential energy analysis, Van der
      Waals (VDW) energy analysis and electrostatic energy analysis, and in addition,
      consideration of the hydrogen bonds and hydrophobic contacts that are involved.
      Based on these analyses, the residues His122 and Lys140 of beta1 and Glu 66, Asn
      131, Asp 118, Glu 120, Glu133, Asn135, Ser 137 of beta3 were predicted to play a
      functional role. 

PMID- 24581801
TI  - Could pseudogenes be widespread in ants? Evidence of numts in the leafcutter ant
      Acromyrmex striatus (Roger, 1863) (Formicidae: Attini).
AB  - The incorporation of fragments of mitochondrial DNA (mtDNA) in the nuclear
      genome, known as numts (nuclear mitochondrial pseudogenes), undermines general
      assumptions concerning the use of mtDNA in phylogenetic and phylogeographic
      studies. Accidental amplifications of these nuclear copies instead of the
      mitochondrial target can lead to crucial misinterpretations, thus the correct
      identification of numts and their differentiation from true mitochondrial
      sequences are important in preventing this kind of error. Our goal was to
      describe the existence of cytochrome b (cytb) numts in the leafcutter ant
      Acromyrmex striatus (Roger, 1863). PCR products were directly sequenced using a
      pair of universal primers designed to amplify the cytb gene of these insects.
      Other species of leafcutter ants were also sequenced. The sequences were analyzed
      and the numts were identified by the presence of double peaks, indels and
      premature stop codons. Only A. striatus clearly showed the presence of numts,
      while the other species displayed the expected amplification of the mtDNA cytb
      gene target using the same primer pair. We hope that our report will highlight
      the benefits and challenges of using mtDNA in the molecular phylogenetic
      reconstruction and phylogeographic studies of ants, while establishing the
      importance of numts reports for future studies. 

PMID- 24581802
TI  - Detection of a Usp-like gene in Calotropis procera plant from the de novo
      assembled genome contigs of the high-throughput sequencing dataset.
AB  - The wild plant species Calotropis procera (C. procera) has many potential
      applications and beneficial uses in medicine, industry and ornamental field. It
      also represents an excellent source of genes for drought and salt tolerance.
      Genes encoding proteins that contain the conserved universal stress protein (USP)
      domain are known to provide organisms like bacteria, archaea, fungi, protozoa and
      plants with the ability to respond to a plethora of environmental stresses.
      However, information on the possible occurrence of Usp in C. procera is not
      available. In this study, we uncovered and characterized a one-class A Usp-like
      (UspA-like, NCBI accession No. KC954274) gene in this medicinal plant from the de
      novo assembled genome contigs of the high-throughput sequencing dataset. A number
      of GenBank accessions for Usp sequences were blasted with the recovered de novo
      assembled contigs. Homology modelling of the deduced amino acids (NCBI accession
      No. AGT02387) was further carried out using Swiss-Model, accessible via the
      EXPASY. Superimposition of C. procera USPA-like full sequence model on Thermus
      thermophilus USP UniProt protein (PDB accession No. Q5SJV7) was constructed using
      RasMol and Deep-View programs. The functional domains of the novel USPA-like
      amino acids sequence were identified from the NCBI conserved domain database
      (CDD) that provide insights into sequence structure/function relationships, as
      well as domain models imported from a number of external source databases (Pfam,
      SMART, COG, PRK, TIGRFAM). 

PMID- 24581803
TI  - Effects of phenanthrene on seed germination and some physiological activities of
      wheat seedling.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are one of the highly persistent organic
      pollutants, and they are toxic to plants and other living organisms, including
      human beings. To analyze the response of higher plant to PAHs, we investigated
      the effects of phenanthrene (PHE) on seed germination and various physiological
      changes of wheat seedlings. Specifically, we investigated growth, chlorophyll
      content, lipid peroxidation (LPO), activities of antioxidant enzymes and H2O2
      accumulation. The results showed that PHE inhibited seed germination, affected
      the growth and chlorophyll level of wheat seedlings. Furthermore, PHE elevated
      the levels of LPO and induced H2O2 accumulation in leaf tissues in a dose
      dependent manner, accompanied by the changes in the antioxidant status. The
      activities of antioxidant enzymes, including superoxide dismutase (SOD), catalase
      (CAT) and glutathione peroxidase (GPX), displayed a decreasing trend with the
      increasing of PHE concentration. The results indicated that PHE could exert
      oxidative damages in the early development stage of wheat and the harmfulness
      occurred mainly in samples with higher concentrations of PHE. 

PMID- 24581804
TI  - Plant adaptation to extreme environments: the example of Cistus salviifolius of
      an active geothermal alteration field.
AB  - Cistus salviifolius is able to colonise one of the most extreme active geothermal
      alteration fields in terms of both soil acidity and hot temperatures. The
      analyses of morpho-functional and physiological characters, investigated in
      leaves of plants growing around fumaroles (G leaves) and in leaves developed by
      the same plants after transfer into growth chamber under controlled conditions (C
      leaves) evidenced the main adaptive traits developed by this pioneer plant in a
      stressful environment. These traits involved leaf shape and thickness, mesophyll
      compactness, stomatal and trichome densities, chloroplast size. Changes of
      functional and physiological traits concerned dry matter content, peroxide and
      lipid peroxidation, leaf area, relative water and pigment contents. A higher
      reducing power and antioxidant enzymatic activity were typical of G leaves.
      Though the high levels of stress parameters, G leaves showed stress-induced
      specific morphogenic and physiological responses putatively involved in their
      surviving in active geothermal habitats. 

PMID- 24581805
TI  - Dual-histidine kinases in basidiomycete fungi.
AB  - Dual-histidine kinases (HKs) are complex hybrid HKs containing in a single
      polypeptide two HK transmitter modules (T) and two-response regulator received
      domains (R) that are combined in a TRTR geometry. In fungi, this protein family
      is limited to some particular species of the phylum Basidiomycota and absent in
      the other phyla. This study extends the investigation of dual-HKs to 80 fully
      sequenced genomes of basidiomycetes, analyzing their distribution, domain
      architecture and phylogenetic relationships. Moreover, similarly to dual-HKs of
      basidiomycetes, several species of bacteria were found that contain hybrid HKs
      with a TRTR domain architecture encoded in a single gene. 

PMID- 24581806
TI  - A comparative analysis of Alexandrium catenella/tamarense blooms in Annaba Bay
      (Algeria) and Thau lagoon (France); phosphorus limitation as a trigger.
AB  - Environmental conditions ultimately leading to blooms of the toxic dinoflagellate
      Alexandrium catenella/tamarense were investigated at two Mediterranean sites
      (Annaba Bay, Algeria and Thau lagoon, France). Three years were examined in
      details: 1992 (a pre-Alexandrium period), 2002 (a year with the first bloom in
      Annaba) and 2010 (a year with a major bloom in Annaba). Most conditions were
      similar, but ammonium concentrations were much higher in Annaba (up to 100MUM)
      than in Thau (up to 10MUM). First records of A. catenella/tamarense were in 1995
      for Thau and 2002 for Annaba, and coincided with soluble reactive phosphorus
      (SRP) decreasing below a concentration of about 1MUM. No other environmental
      variable could be related to those blooms. Thus, it is likely that the large
      reductions in SRP at both sites led to phosphorus limitation of a certain number
      of phytoplankton species and favored the development of A. catenella/tamarense. 

PMID- 24581807
TI  - Why the aphid Aphis spiraecola is more abundant on clementine tree than Aphis
      gossypii?
AB  - Aphis spiraecola and Aphis gossypii cause harmful damages on clementine tree
      orchards. Weekly surveys measured the abundance of aphids (larvae, winged and
      wingless adults) as well as of auxiliary insects and parameters of energy
      metabolism. Correlatively, soluble carbohydrates, total free amino acids, free
      proline and condensed tannins were quantified in control and infested leaves.
      Both aphid species showed parallel temporal variations, but A. spiraecola was
      consistently more abundant regardless of the stage. Amino acids had a positive
      effect on both aphid species abundance, but neither condensed tannins nor
      auxiliary insects seemed to modulate aphid populations. Interestingly, the leaf
      carbohydrate content was positively correlated with the abundance of A.
      spiraecola, but not with that of A. gossypii. Moreover, A. gossypii's abundance
      was significantly down-regulated by high proline concentrations. Thus, the higher
      abundance of A. spiraecola could be explained by a better tolerance to high
      proline contents and a better conversion of foliar energy metabolites. 

PMID- 24581808
TI  - Description of a new bat species of the tribe Scotonycterini (Chiroptera,
      Pteropodidae) from Southwestern Cameroon.
AB  - The tribe Scotonycterini is currently composed of three fruit bat species of the
      family Pteropodidae (Mammalia, Chiroptera) characterized by white fur patches on
      the head, specifically around the nose and behind the eyes: Scotonycteris
      zenkeri, S. ophiodon and Casinycteris argynnis. Herein a new species is
      described, Casinycteris campomaanensis sp. nov., based on female specimen
      collected in 2007 near the village Nkoelon-Mvini close to the Campo-Ma'an
      National Park, southwestern Cameroon. It is readily distinguished from the three
      other species of Scotonycterini by its body size and craniodental
      characteristics. Molecular analyses based on the complete mitochondrial
      cytochrome b gene indicate that the new species is the sister-group to C.
      argynnis and that the holotype of S. ophiodon is more closely related to
      Casinycteris than to S. zenkeri, rendering the genus Scotonycteris paraphyletic.
      Based on these results, morphological characters within the tribe Scotonycterini
      were reassessed and a new classification is proposed, in which the new species
      and S. ophiodon are placed in the genus Casinycteris. 

PMID- 24581809
TI  - A new species of scorpion of the genus Neoscorpiops Vachon, 1980 (Scorpiones:
      Euscorpiidae) from India.
AB  - A new species of scorpion of the genus Neoscorpiops Vachon, 1980 is described
      from Northern Maharashtra. Neoscorpiops maharashtraensis sp. nov. is a medium
      sized scorpion species ranging from 36 to 42mm. Carapace, mesosoma and metasoma
      brown, legs and telson yellow; pedipalp in a shade of brown with carinae dark
      drown to black. Granulation on carapace coarse, with a few smooth patches; on
      mesosoma, which is restricted to the posterior half. Anterior margin of carapace
      with a moderately deep "U"-shaped emargination medially lacking elevated edges.
      Pectines well developed 7/7. Trichobothria on patella ventral 13-16. Pedipalp
      chela narrow and elongate in males, length-to-width ratio in males is 4.86-5.05. 

PMID- 24581810
TI  - Pre-operative MR evaluation of features that indicate the need of adjuvant
      therapies in early stage cervical cancer patients. A single-centre experience.
AB  - OBJECTIVES: This study compared the MR measurement of minimum uninvolved cervical
      stroma and maximum stromal invasion, and the detection of positive lymph nodes
      with the pathological results. In addition, tumour type and grade were correlated
      with nodal status and apparent diffusion coefficient (ADC) values. METHODS:
      Patients who underwent surgery and MR at our centre for early stage cervical
      cancer (FIGO IA1-IIB) were included. Data recorded included: age, date of MR,
      clinical FIGO (International Federation of Gynacology and Obstetrics) stage,
      histological type and grade, adjuvant therapy, pre-surgical conisation. MR
      evaluation included: measurement of the minimum uninvolved stroma, maximum
      thickness of stromal involvement, presence and site of positive pelvic lymph
      nodes, calculation of ADC values. Statistical analysis was performed to compare
      MR and pathological results. The agreement between MR and pathology in measuring
      depth of stromal invasion was analysed by Bland-Altman plot, calculating the
      limits of agreement (LoA). RESULTS: 113/217 patients underwent adjuvant
      therapies. Sensitivity, specificity, positive predictive value, negative
      predictive value and accuracy of MR in evaluation of minimum thickness of
      uninvolved cervical stroma were 88%, 75%, 70%, 90% and 80%; the same values in
      evaluation of pelvic positive lymph nodes were 64%, 85%, 65%, 84% and 78%. The
      mean difference between MR and pathological results in measuring maximum depth of
      stromal invasion was -0.65mm (95% LoA: -9.37mm; 8.07mm). Depth of stromal
      invasion was strongly related to positive nodal status (p<0.001). ADC values
      (available in 51/217 patients) were not associated with the features assessed.
      CONCLUSIONS: Pre-surgical MR is accurate (80%) in evaluating the minimum
      thickness of uninvolved cervical stroma; MR measurements of maximum depth of
      stromal invasion differed +/-9mm from the pathological results in 95% of cases.
      Furthermore, a strong association was found between the depth of stromal invasion
      and the presence of positive lymph nodes, suggesting that inclusion of these
      measurements in the MR report might guide the choice of the best treatment option
      for early cervical cancer patients.

PMID- 24581811
TI  - Up-regulation of pro-inflammatory factors by HP-PRRSV infection in microglia:
      implications for HP-PRRSV neuropathogenesis.
AB  - Atypical porcine reproductive and respiratory syndrome (PRRS) caused by a highly
      pathogenic PRRS virus (HP-PRRSV) is characterized by high fever, high morbidity,
      high mortality, and associated with severe neurological symptoms. Microglia are
      the resident innate immune cells in central nervous system (CNS), and their
      activation has been implicated as an important contributor to the pathogenesis of
      CNS diseases. In the present study, we successfully cultured porcine microglia
      and demonstrated that microglia could support PRRSV infection and replication in
      vitro. We further showed that HP-PRRSV infection significantly up-regulated the
      key inflammatory factors including IL-1beta, TNF-alpha, IL-6, IL-12, IL-8,
      CXCL10, MCP-1, CCL3, CCL4, and CCL5 in cultured microglia as well as in the CNS
      of HP-PRRSV-infected pigs. The transcription factors NF-kappaB and AP-1, which
      are widely reported to regulate cytokine and chemokine productions, were
      activated by HP-PRRSV infection in microglia. Meanwhile, we found that HP-PRRSV
      induced cellular ROS formation in microglia and ROS scavenger was proved to
      significantly abolish the activation of pro-inflammatory cytokines (IL-1beta, TNF
      alpha, IL-6, and IL-8), suggesting that ROS are crucial for pro-inflammatory gene
      production. Importantly, incubation with supernatants from HP-PRRSV-infected
      microglia cell culture remarkably induced SH-SY5Y neuroblastoma cell death.
      Collectively, these results showed that PRRSV infection induced cytokine and ROS
      up-regulation in microglia, which might contribute to neurotoxicity. These data
      have implications for us to understand the neuropathogenesis of HP-PRRSV in pigs.

PMID- 24581812
TI  - Greater dietary acculturation (dietary change) is associated with poorer current
      self-rated health among African immigrant adults.
AB  - OBJECTIVE: Investigate the relationship between dietary acculturation and current
      self-rated health (SRH) among African immigrants, by country or region of origin.
      DESIGN: Cross-sectional, mixed-methods design using baseline data from
      longitudinal study of immigrants granted legal permanent residence May to
      November, 2003, and interviewed June, 2003 to June, 2004. SETTING: 2003 New
      Immigrant Survey. PARTICIPANTS: African immigrants from a nationally
      representative sample (n = 763) averaged 34.7 years of age and 5.5 years' US
      residency; 56.6% were male, 54.1% were married, 26.1% were Ethiopian, and 22.5%
      were Nigerian. MAIN OUTCOME MEASURE(S): Current SRH (dependent variable) was
      measured using 5-point Likert scale questions; dietary acculturation (independent
      variable) was assessed using a quantitative dietary change scale. ANALYSIS:
      Multivariate logistic regression tested the relationship of dietary acculturation
      with current SRH (alpha = .05; P < .05 considered significant); exploratory
      qualitative subset dietary analysis (n = 60) examined food/beverages consumed pre
      /post-migration. RESULTS: African immigrants reporting moderate dietary change
      since arrival in the US had higher odds of poorer SRH status than immigrants
      reporting low dietary change (odds ratio, 1.903; 95% confidence interval, 1.143
      3.170; P = .01). Among most dietary change groups, there was an increase in fast
      food consumption and decrease in fruit and vegetable consumption. CONCLUSIONS AND
      IMPLICATIONS: Nutrition educators and public health practitioners should develop
      targeted nutrition education for African immigrants who are older, less educated,
      and at increased health risk.

PMID- 24581813
TI  - Discussion map and cooking classes: testing the effectiveness of teaching food
      safety to immigrants and refugees.
AB  - OBJECTIVE: To evaluate the effectiveness of a food safety map as an educational
      method with English language learners. METHODS: English language learner
      community members (n = 73) were assigned randomly to participate in 1 of 3
      experimental conditions: food safety map, cooking class, and control.
      Participants in the food safety map and cooking class conditions completed a pre
      education demographic and cooking history questionnaire, a post-education
      knowledge and intention questionnaire, and a 2-week post-cooking and food safety
      habits assessment. Participants in the control group received no educational
      training but completed the pre- and 2-week post-education assessments. RESULTS:
      The cooking class and the map class were both effective in increasing food safety
      knowledge. Specifically, by comparing with the control group, they significantly
      increased participants' knowledge of safely cooking large meat (chi2 [df = 2, n =
      66] = 40.87; P < .001; V* = .79) and correctly refrigerating cooked food (chi2
      [df = 2, n = 73] = 24.87, P < .001; V* = .58). The two class types generated
      similar positive educational effects on boosting food safety behavioral intention
      (measured right after the class). The data collected 2 weeks after the classes
      suggested that individuals who took the classes followed the suggested food
      behaviors more closely than those in the control group (P < .01). CONCLUSIONS AND
      IMPLICATIONS: The food safety map is simple to use and prepare, beneficial for
      oral and visual learners, and inexpensive. Compared with a food safety cooking
      class, the map produces similar learning and behavioral outcomes.

PMID- 24581814
TI  - Osteoarthritic cartilage lesions in the bovine patellar groove: a macroscopic,
      histological and immunohistological analysis.
AB  - A high percentage of osteoarthritis (OA)-like patellar groove lesions in the
      stifle joint in calcium-deficient bulls has been recently reported. The
      prevalence of these lesions in bulls deficient in or supplemented with calcium
      was compared to findings in culled and healthy bulls to determine whether they
      represent normal anatomical variations, developmental anomalies or OA. It was
      hypothesized that the patellar groove lesions may represent OA. Distal cartilage
      samples from 160 femurs were analysed using a macroscopic Societe Francaise
      d'Arthroscopie (SFA) OA grading system. Samples representing different SFA grades
      were subjected to Osteoarthritis Research Society International (OARSI)
      histological and high-mobility group box 1 (HMGB1) immunohistological OA grading.
      For a qualitative analysis three OA samples were immunostained for interleukin
      (IL)-1beta, matrix metalloproteinase (MMP)-13 and collagenase-produced COL2-3/4M
      neoepitopes. Patellar groove lesions were found in 48% of the femurs and were
      highest in calcium-deficient animals (71%, P<0.001). All three different grading
      systems disclosed OA in culled bulls, but no focal areas of cartilage necrosis.
      OARSI and HMGB1 grades were fairly concordant (Spearman's rho=0.95, P<0.001;
      Cohen's kappa=0.23, P<0.005), both with a slight disparity with the SFA grade
      (rho=0.80 and 0.87, P<0.01; kappa=0.36 and 0.46, P<0.001). IL-1beta, MMP-13 and
      COL2-3/4M staining patterns were compatible with OA. The study showed that
      patellar groove lesions are common in bulls. In all SFA, OARSI and HMGB1 graded
      samples the lesions clearly demonstrated OA and showed OA-typical
      pathophysiology. Arthroscopic SFA grading showed similar changes in calcium
      deficient and calcium-supplemented bulls, but in the absence of a time course
      study and histological data the primary nature of these lesions could not be
      established with certainty.

PMID- 24581815
TI  - Required coefficient of friction during turning at self-selected slow, normal,
      and fast walking speeds.
AB  - This study investigated the relationship of required coefficient of friction to
      gait speed, obstacle height, and turning strategy as participants walked around
      obstacles of various heights. Ten healthy, young adults performed 90 degrees 
      turns around corner pylons of four different heights at their self selected
      normal, slow, and fast walking speeds using both step and spin turning
      strategies. Kinetic data was captured using force plates. Results showed peak
      required coefficient of friction (RCOF) at push off increased with increased
      speed (slow MU=0.38, normal MU=0.45, and fast MU=0.54). Obstacle height had no
      effect on RCOF values. The average peak RCOF for fast turning exceeded the OSHA
      safety guideline for static COF of MU>0.50, suggesting further research is needed
      into the minimum static COF to prevent slips and falls, especially around
      corners. 

PMID- 24581816
TI  - Selective lateral muscle activation in moderate medial knee osteoarthritis
      subjects does not unload medial knee condyle.
AB  - There is some debate in the literature regarding the role of quadriceps
      hamstrings co-contraction in the onset and progression of knee osteoarthritis.
      Does co-contraction during walking increase knee contact loads, thereby causing
      knee osteoarthritis, or might it be a compensatory mechanism to unload the medial
      tibial condyle? We used a detailed musculoskeletal model of the lower limb to
      test the hypothesis that selective activation of lateral hamstrings and
      quadriceps, in conjunction with inhibited medial gastrocnemius, can actually
      reduce the joint contact force on the medial compartment of the knee, independent
      of changes in kinematics or external forces. "Baseline" joint loads were computed
      for eight subjects with moderate medial knee osteoarthritis (OA) during level
      walking, using static optimization to resolve the system of muscle forces for
      each subject's scaled model. Holding all external loads and kinematics constant,
      each subject's model was then perturbed to represent non-optimal "OA-type"
      activation based on mean differences detected between electromyograms (EMG) of
      control and osteoarthritis subjects. Knee joint contact forces were greater for
      the "OA-type" than the "Baseline" distribution of muscle forces, particularly
      during early stance. The early-stance increase in medial contact load due to the
      "OA-type" perturbation could implicate this selective activation strategy as a
      cause of knee osteoarthritis. However, the largest increase in the contact load
      was found at the lateral condyle, and the "OA-type" lateral activation strategy
      did not increase the overall (greater of the first or second) medial peak contact
      load. While "OA-type" selective activation of lateral muscles does not appear to
      reduce the medial knee contact load, it could allow subjects to increase knee
      joint stiffness without any further increase to the peak medial contact load.

PMID- 24581817
TI  - Effect of non-uniform thickness of samples in stress relaxation tests under
      unconfined compression of samples of articular discs.
AB  - A precise information of the biomechanical properties of soft tissues is required
      to develop a suitable simulation model, with which the distribution of stress and
      strain in the complex structures can be estimated. Many soft tissues have been
      mechanically characterized by stress relaxation tests under unconfined or
      confined compression. In general, full-thickness samples are extracted to reduce
      the damage in the tissue as much as possible. However, it is not guaranteed that
      these samples have a uniform thickness or, in other words, planar parallel faces.
      In particular, in the articular disc of the temporomandibular joint, many studies
      can be found testing full-thickness samples for which that thickness is known to
      be non-uniform, while making the assumption of uniaxial stress state to extract
      the mechanical properties from those tests. That inaccuracy may have a strong
      influence in some cases and needs a profound revision. The main goal of this work
      is to quantify the error committed in that assumption and the influence of the
      variation of thickness on that error in a particular test: stress relaxation
      tests under unconfined compression. Based on this error and defining an allowable
      tolerance, a criterion is established to reject samples depending on their aspect
      ratio. 

PMID- 24581818
TI  - [Genital lymphedema associated with Crohn's disease].
AB  - INTRODUCTION: Crohn's disease is a chronic inflammatory intestinal pathology
      which can be associated to different extra-digestive manifestations. We reported
      a case of recurrent genital lymphedema leading to Crohn's disease diagnosis. CASE
      REPORT: A 49-year-old man was referred for increased penis and scrotal volume,
      associated with recurrent febrile flare during the 10 previous years. Clinically,
      we noted an inflammatory penis and scrotum lymphedema. Clinical urological
      examination, and biological, bacteriological, computer-tomography examinations
      were negative. Metastatic Crohn's disease was diagnosed in association with
      concomitant severe terminal ileitis. Treatment with corticosteroids and
      azathioprine resulted in significant decrease of inflammatory genital lymphedema.
      CONCLUSION: Genital inflammatory lymphedema occurs during inflammatory,
      infectious, and tumor diseases. Some cases of metastatic genital lymphedema
      related to Crohn's disease are described, most often in children. Inflammatory
      genital lymphedema associated with gastrointestinal symptoms may suggest Crohn's
      disease.

PMID- 24581819
TI  - [Urticaria: diagnosis and treatment].
AB  - Urticaria is a common inflammatory skin disease. It is clinically defined as the
      occurrence of transient papular skin and/or mucosal lesions or subcutaneous
      lesions called angioedema. Chronic urticaria is defined as a clinical course over
      more than 6weeks. Different clinical forms of urticaria can coexist in the same
      patient. Urticaria results of mast cell activation. The diagnosis of urticaria is
      based on clinical examination. An allergic etiology for acute urticaria, although
      rare, is always to find and remove. Chronic urticaria is not allergic. Diagnosis
      is based on questioning and a careful clinical examination to rule out
      differential diagnoses. Few diagnostic tests are necessary for diagnosis and
      management, and are especially useful in case of doubtful diagnosis. The
      treatment of urticaria is symptomatic and based on anti-H1 second generation
      antihistamines as first-line therapy. In some chronic urticarial, antihistamines
      up dosing may be necessary. In the majority of patients, this treatment is
      sufficient to control chronic urticaria. In case of antihistamines failure, other
      treatment particularly immunomodulatory treatments can be offered in specialized
      departments. 

PMID- 24581820
TI  - Depression-related differences in lean body mass distribution from National
      Health and Nutrition Examination Survey 2005-2006.
AB  - BACKGROUND: Although the association between depression and body composition has
      been widely discussed, the effects of depression on lean body mass (LBM) are
      unclear. The present study aimed to investigate the association of depression
      with LBM. METHODS: The study included 2406 participants aged 18-69 years. The sex
      and body mass index (BMI) stratified analysis of covariance was performed to
      compare total LBM and percentage LBM (%LBM) in subjects with different depression
      score levels. Multiple linear regression analysis was conducted to estimate the
      association between depression score and serum albumin level. RESULTS: An
      analysis of covariance stratified by sex showed that participants with moderate
      to-severe depression had significantly decreased total LBM and total and regional
      %LBM in men, except for total LBM and percentage gynoid LBM, which was observed
      in women. In the BMI stratified analysis of covariance, depression was
      significantly associated with decreased total and regional %LBM and with
      increased total and regional percentage fat body mass. In people with
      BMI>=25kg/m(2), the associations between depression or depressive syndrome and
      LBM, and total and regional %LBM are stronger compared to those with
      BMI<25kg/m(2). Multiple linear regression analysis showed that depression score
      was significantly negatively associated with serum albumin level. LIMITATIONS:
      This is a cross-sectional study based on a general population, some information
      about clinical diagnosis and medication use is not available. CONCLUSIONS:
      Depression had a significant negative association with LBM and serum albumin
      level.

PMID- 24581821
TI  - Affect intensity measure in bipolar disorders: a multidimensional approach.
AB  - BACKGROUND: Emotional dysregulation, characterized by high levels of both arousal
      and intensity of emotional responses, is a core feature of bipolar disorders
      (BDs). In non-clinical populations, the 40-item Affect Intensity Measure (AIM)
      can be used to assess the different dimensions of emotional reactivity. METHODS:
      We analyzed the factor structure of the AIM in a sample of 310 euthymic patients
      with BD using Principal Component Analysis and examined associations between AIM
      sub-scale scores and demographic and illness characteristics. RESULTS: The French
      translation of the AIM demonstrated good reliability. A four-factor solution
      similar to that reported in non-clinical samples (Positive Affectivity,
      Unpeacefulness [lack of Serenity], Negative Reactivity, Negative Intensity),
      explained 47% of the total variance. Age and gender were associated with
      Unpeacefulness and Negative reactivity respectively. 'Unpeacefulness' was also
      positively associated with psychotic symptoms at onset (p=0.0006), but negatively
      associated with co-morbid substance misuse (p=0.008). Negative Intensity was
      positively associated with social phobia (p=0.0005). LIMITATIONS: We cannot
      definitively exclude a lack of statistical power to classify all AIM items.
      Euthymia was carefully defined, but a degree of 'contamination' of the self
      reported levels of emotion reactivity may occur because of subsyndromal BD
      symptoms. It was not feasible to control for the possible impact of on-going
      treatments. CONCLUSIONS: The AIM scale appears to be a useful measure of
      emotional reactivity and intensity in a clinical sample of patients with BD,
      suggesting it can be used in addition to other markers of BD characteristics and
      sub-types.

PMID- 24581822
TI  - Low baseline salivary alpha-amylase in drug-naive patients with short-illness
      duration first episode major depressive disorder.
AB  - BACKGROUND: Altered monoamine neurotransmission accompanied by hypothalamic
      pituitary-adrenal axis dysfunction and autonomic nervous system hyperactivity
      have been associated with major depressive disorder (MDD). Salivary alpha-amylase
      (sAA) is indicative of autonomic activation and reflects central noradrenergic
      activity. Scarce studies on sAA in MDD produce confounded results and no data is
      available regarding baseline sAA activity. METHODS: The basal, non-stimulated sAA
      activity was studied in this cross-sectional case-control study on 20 non-late
      life adult, short-illness-duration first-episode, treatment-naive MDD patients
      and in 20 age- and sex-matched healthy controls. Depressed patients showed a
      basal score in the Hamilton Rating Scale for Depression (HAMD-17) higher than 20.
      RESULTS: The sAA was significantly lower in depressed individuals as compared to
      controls (p=0.011). In post hoc analysis significantly lower sAA was present in
      melancholic MDD (p=0.016) as related to controls whereas no difference was seen
      between non-melancholic MDD patients and controls. The sAA activity was not
      significantly correlated neither with duration nor the severity of depressive
      symptoms as measured by the total HAMD-17 score. LIMITATIONS: The current study
      is limited by its cross-sectional design, small sample size, and factors related
      to saliva sampling methodology. CONCLUSION: Low baseline sAA levels were found in
      MDD in basal, non-stimulated conditions. The study provides no support for
      elevated sAA in drug-naive patients with short-illness-duration first episode
      MDD. The results support the evidence for decreased central noradrenergic
      transmission in MDD when sAA activity is considered indicative of central
      noradrenergic function.

PMID- 24581823
TI  - Structure of the DSM-5 generalized anxiety disorder criteria among a large
      community sample of worriers.
AB  - BACKGROUND: There is growing empirical and clinical consensus that many
      psychiatric disorders are continuous in nature. The DSM-5 however makes a
      categorical distinction between subthreshold and threshold cases of generalized
      anxiety disorder (GAD). This study tested the a priori assumption that the DSM-5
      criteria identify a break in psychopathology between subthreshold and threshold
      cases of GAD. METHODS: Respondents of the 2007 National Survey of Mental Health
      and Well Being who self-identified as worriers were selected for analyses
      (n=1738). The GAD criteria were assessed using the World Mental Health version of
      the Composite International Diagnostic Interview. Item response, latent class and
      factor mixture models were estimated to assess the structure of the GAD criteria.
      RESULTS: The relative fit of the latent variable models suggested that a single
      continuous factor explains the way that worriers endorse the GAD criteria.
      However, the similar psychometric properties of the GAD criteria suggested that
      the GAD criteria impose a relatively finite threshold over this dimension of
      severity. LIMITATIONS: Although these structural analyses did not identify a
      break in psychopathology between subthreshold and threshold cases of GAD based on
      the way that respondents endorsed the DSM-5 criteria, it is possible that
      structural analyses of risk factors and other clinical correlates of GAD may
      identify such a break in the future. CONCLUSIONS: These data suggest that the DSM
      5 GAD criteria lend themselves to making both categorical decisions about cases
      as well as being indices of a continuum of severity.

PMID- 24581824
TI  - The relationship between interpersonal problems, therapeutic alliance, and
      outcomes following group and individual cognitive behaviour therapy.
AB  - BACKGROUND: Cognitive behavioural therapy (CBT) is efficacious, but there remains
      individual variability in outcomes. Patient's interpersonal problems may affect
      treatment outcomes, either directly or through a relationship mediated by helping
      alliance. Interpersonal problems may affect alliance and outcomes differentially
      in individual and group (CBGT) treatments. The main aim of this study was to
      investigate the relationship between interpersonal problems, alliance, dropout
      and outcomes for a clinical sample receiving either individual or group CBT for
      anxiety or depression in a community clinic. METHODS: Patients receiving
      individual CBT (N=84) or CBGT (N=115) completed measures of interpersonal
      problems, alliance, and disorder specific symptoms at the commencement and
      completion of CBT. RESULTS: In CBGT higher pre-treatment interpersonal problems
      were associated with increased risk of dropout and poorer outcomes. This
      relationship was not mediated by alliance. In individual CBT those who reported
      higher alliance were more likely to complete treatment, although alliance was not
      associated with symptom change, and interpersonal problems were not related to
      attrition or outcome. LIMITATIONS: Allocation to group and individual therapy was
      non-random, so selection bias may have influenced these results. Some analyses
      were only powered to detect large effects. Helping alliance ratings were high, so
      range restriction may have obscured the relationship between helping alliance,
      attrition and outcomes. CONCLUSIONS: Pre-treatment interpersonal problems
      increase risk of dropout and predict poorer outcomes in CBGT, but not in
      individual CBT, and this relationship is not mediated by helping alliance.
      Stronger alliance is associated with treatment completion in individual, but not
      group CBT.

PMID- 24581825
TI  - Effect of quetiapine XR on depressive symptoms and sleep quality compared with
      lithium in patients with bipolar depression.
AB  - BACKGROUND: Bipolar depression is one of the most serious psychiatric conditions.
      In addition, sleep disturbance in bipolar disorder is common, and therapeutic
      agents restoring sleep disturbances in bipolar disorder patients will be
      clinically beneficial. In the current study, we compared the effect of quetiapine
      XR with lithium on depressive symptoms and sleep in bipolar depression patients
      during 8 weeks of trial. METHODS: An open-label, randomized comparison of sleep
      activity and depressive symptoms between 8-week quetiapine XR monotherapy and
      lithium monotherapy for bipolar depression was conducted. Each assessment
      consisted of HDRS-17, Clinical Global Impression-severity (CGI-S), and self
      reported Pittsburgh Sleep Quality Index (PSQI). Actigraphy-measured sleep
      parameters were assessed. RESULTS: A total of 42 patients (35.7+/-10.9 years;
      gender: male 15, female 27) with bipolar depression were screened out. Out of 42
      patients, six patients were excluded before randomization. After randomization,
      seven patients were withdrawn. Twenty-nine patients with more than two visits
      after randomization (lithium group: 17, quetiapine XR group: 12, mean age: 36.1+/
      10.4, gender: male 13, female 16) were included in the final analysis. In both
      groups, Hamilton Depression Rating Scale (HDRS) scores were significantly
      decreased at weeks 1, 2, 4, 6, and 8 compared with baseline. Remission rate
      (HDRS<=7) in the quetiapine XR was significantly higher than that of the lithium
      group. In the quetiapine XR group, PSQI scores at weeks 1, 2, 4, 6, and 8 was
      significantly decreased compared with baseline. Sleep efficiency at weeks 6 and 8
      was significantly increased. WASO at week 8 was significantly decreased.
      LIMITATIONS: First, the present study was conducted with the relatively small
      number of study subjects. Second, bias could have affected the study results due
      to its open-label design. Third, study subjects were made up of high proportion
      of bipolar II disorder patients. CONCLUSIONS: Quetiapine XR monotherapy was more
      effective in treating bipolar depression than lithium. In particular, quetiapine
      XR treatment improved both subjective and objective sleep quality in patients
      with bipolar depression. However, relationship between favorable sleep quality
      and depressive symptom improvement were limited.

PMID- 24581826
TI  - A preliminary report of increased plasma levels of IL-33 in bipolar disorder:
      further evidence of pro-inflammatory status.
AB  - BACKGROUND: Recent findings suggest an important role for inflammation in the
      neurobiology of bipolar disorder (BD). Interleukin 33 (IL-33) is a cytokine with
      multiple functions and may act as a nuclear factor regulating transcription and
      as an "alarmin". IL-33 exerts part of its function through the receptor ST2 that
      also exists in a soluble form (sST2). This study was performed to evaluate IL-33
      and sST2 plasma levels in BD patients. METHODS: We evaluated IL33 and sST2 plasma
      levels of 46 BD patients (23 in euthymia and 23 in mania) and 23 healthy controls
      using enzyme-linked immunosorbent assay (ELISA). BD patients were age and gender
      matched healthy controls. RESULTS: IL-33 levels were higher in BD patients
      (p=0.02) but there was no difference in sST2 (p=0.55). IL33 and sST2 plasma
      levels were not correlated with age, neither was influenced by clinical
      comorbidities nor medications in use. CONCLUSION: These findings corroborate the
      view of BD as a multisystem condition with a proinflammatory profile.

PMID- 24581827
TI  - Air pollution as a risk factor for depressive episode in patients with
      cardiovascular disease, diabetes mellitus, or asthma.
AB  - BACKGROUND: There is currently insufficient evidence to confirm the effect of
      ambient air pollution on mental disorders, especially among susceptible
      populations. This study investigated the short-term effect of ambient air
      pollution on the risk of depressive episode and the effect modification across
      disease subpopulations. METHODS: Subjects who visited the emergency department
      (ED) for depressive episode from 2005 to 2009 (n=4985) in Seoul, Republic of
      Korea were identified from medical claims data. We conducted a time-stratified
      case-crossover study using conditional logistic regression. Subgroup analyses
      were conducted after the subjects were stratified by underlying disease
      (cardiovascular disease, diabetes mellitus, chronic obstructive pulmonary
      disease, asthma, and depressive disorder). The risk was expressed as an odds
      ratio (OR) per 1 standard deviation of each air pollutant. RESULTS: SO2, PM10,
      NO2, and CO were positively associated with ED visits for depressive episode. The
      maximum risk was observed in the distributed lag 0-3 model for PM10 (OR, 1.120;
      95% confidence interval, 1.067-1.176). PM10, NO2, and CO significantly increased
      the risks of ED visits for depressive episode in subjects with either underlying
      cardiovascular disease, diabetes mellitus, asthma, or depressive disorder.
      LIMITATIONS: Our data may include a misclassification bias due to the validity of
      a diagnosis determined from medical services utilization data. CONCLUSIONS: SO2,
      PM10, NO2, and CO significantly increased the risk of ED visits for depressive
      episode, especially among individuals with pre-existing cardiovascular disease,
      diabetes mellitus, or asthma.

PMID- 24581828
TI  - Emotion regulation strategies in bipolar II disorder and borderline personality
      disorder: differences and relationships with perceived parental style.
AB  - BACKGROUND: Bipolar II disorder (BP II) and Borderline Personality Disorder (BPD)
      share common features and can be difficult to differentiate, contributing to
      misdiagnosis and inappropriate treatment. Research contrasting phenomenological
      features of both conditions is limited. The current study sought to identify
      differences in emotion regulation strategies in BP II and BPD in addition to
      examining relationships with perceived parental style. METHOD: Participants were
      recruited from a variety of outpatient and community settings. Eligible
      participants required a clinical diagnosis of BP II or BPD, subsequently
      confirmed via structured diagnostic interviews assessing DSM-IV criteria.
      Participants completed a series of self-reported questionnaires assessing emotion
      regulation strategies and perceived parental style. RESULTS: The sample comprised
      48 (n=24 BP II and n=24 BPD) age and gender-matched participants. Those with BPD
      were significantly more likely to use maladaptive emotion regulation strategies,
      less likely to use adaptive emotion regulation strategies, and scored
      significantly higher on the majority of (perceived) dysfunctional parenting sub
      scales than participants with BP II. Dysfunctional parenting experiences were
      related to maladaptive emotion regulation strategies in participants with BP II
      and BPD, however differential associations were observed across groups.
      LIMITATIONS: Relatively small sample sizes; lack of a healthy control comparator
      group; lack of statistical control for differing sociodemographic and clinical
      characteristics, medication and psychological treatments; no assessment of state
      or trait anxiety; over-representation of females in both groups limiting
      generalisability of results; and reliance on self-report measures. CONCLUSIONS:
      Differences in emotion regulation strategies and perceived parental style provide
      some support for the validity of distinguishing BP II and BPD. Development of
      intervention strategies targeting the differing forms of emotion regulatory
      pathology in these groups may be warranted.

PMID- 24581830
TI  - rTMS in resistant mixed states: an exploratory study.
AB  - BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) has shown
      efficacy in resistant unipolar depression, but its efficacy in bipolar disorders
      has not yet been extensively investigated. Mixed episodes are reported in up to
      40% of acute bipolar admissions and are associated with severe psychopathology,
      comorbidity, high risk of suicide and poor treatment response. Right low
      frequency rTMS (LF-rTMS) as an augmentation treatment might be effective for
      mixed states. METHODS: Forty patients were treated during a 4-week period with a
      mood stabilizer and subsequent rTMS (low frequency stimulation - 1Hz - applied to
      the right Dorso-Lateral Prefrontal Cortex (DLPFC)) as add-on treatment for 3
      weeks. Response to LF-rTMS was assessed by the Hamilton Depression Rating Scale
      (HAM-D), the Young Mania Rating Scale (YMRS) and the Clinical Global Impressions
      Bipolar Version (CGIBP) subscales. ANOVA with repeated measures performed on HAM
      D, YMRS and CGI-BP subscales "change from the preceding phase" and "severity of
      illness" showed a statistically significant time effect from the baseline to the
      endpoint. RESULTS: For the HAM-D there was a 46.6% responder rate, of which 28.6%
      was remitted, while for the YMRS there was a 15% responder rate, all of which was
      remitted. LIMITATIONS: The open label-design of our study and the lack of a sham
      controlled group represent a methodological limitation. CONCLUSIONS: The results
      suggest that LF-rTMS on the right DLFC might be a potential augmentation strategy
      in the treatment of both depressive and manic symptoms in mixed states.

PMID- 24581829
TI  - Impairment of work productivity in panic disorder patients.
AB  - BACKGROUND: Panic disorder (PD) has a critical impact on productivity at the
      workplace. This study aimed to identify the lost productivity time (LPT) for
      patients with PD. It also assessed change in LPT for patients with PD after 12
      weeks of treatment with Selective Serotonin Reuptake Inhibitors (SSRIs), compared
      with healthy controls. METHODS: Working patients diagnosed with PD without other
      major medical or psychiatric illness were enrolled at outpatient psychiatric
      clinics (N=108). Age and sex-matched healthy controls were recruited through
      advertisement (N=108). Health and productivity, PD symptoms, and depressive
      symptoms were assessed using the Korean version of the World Health
      Organization's Health and Work Performance Questionnaire (HPQ), the Panic
      Disorder Severity Scale (PDSS), and the Hamilton Rating Scales for Depression
      (HAM-D), respectively at baseline, week 4, and week 12. RESULTS: At baseline, the
      PD group showed significantly higher LPT compared to the control group (103.02
      vs. 47.28h in the past 4 weeks). After 12 weeks of treatment, the PD group
      displayed significant clinical improvement as well as improved productivity with
      a marked reduction in LPT. Among the patients who completed the treatment, LPT
      due to PD was reduced from 104.38 to 55.15h in the past 4 weeks. LIMITATIONS:
      There may be selection bias due to case-control study design. CONCLUSIONS: These
      data suggest that, after the treatment, there was significant improvement in
      clinical symptoms, and that productivity loss due to PD was almost entirely
      recovered to the level of healthy controls after 12 weeks of psychiatric
      outpatient treatment.

PMID- 24581833
TI  - Further evidence for plasma progranulin as a biomarker in bipolar disorder.
AB  - BACKGROUND: A recent study suggested that progranulin (encoded by the fronto
      temporal dementia risk gene GRN) plasma levels are decreased in bipolar disorder
      (BD). Replication of this finding is however lacking. METHODS: Progranulin plasma
      levels of bipolar patients (n=104) and healthy controls (n=80) were measured by
      enzyme-linked immunosorbent assay (ELISA). Participants were also genotyped for
      three single nucleotide polymorphisms (SNPs) in the GRN gene (rs2879096,
      rs4792938 and rs5848), and the effect of genetic variation on progranulin levels
      was examined. RESULTS: Plasma progranulin levels were decreased in BD (ANCOVA,
      p=0.001). Furthermore, age was significantly and positively correlated with
      plasma progranulin (Pearson's correlation, r=0.269, p<0.001). Also, lithium
      treatment but no other medication had a significant effect on progranulin plasma
      levels (ANCOVA, p=0.007). Specifically in BD, the GRN SNP rs5848 was associated
      with progranulin plasma levels (Kruskal-Wallis test, p<0.005). LIMITATIONS:
      Subgroup analysis regarding bipolar I vs. bipolar II subtype and polarity of the
      episode at sampling (manic vs. depressed vs. mixed vs. rapid cycling vs.
      euthymic) could only be performed with limited validity due to the relatively
      small sample size. The suitability of peripheral progranulin as a biomarker for
      BD is limited due to the overlap between patients and controls. CONCLUSION: The
      findings strengthen the evidence for progranulin being involved in
      pathomechanisms of bipolar disorder, and suggest a genetic determinant of
      progranulin concentrations that is relevant specifically in bipolar patients.

PMID- 24581832
TI  - Exploring the associations between genetic variants in genes encoding for
      subunits of calcium channel and subtypes of bipolar disorder.
AB  - BACKGROUND: Associations of two voltage-gated calcium channel (Cav) genes,
      CACNA1C and CACNB2, were identified for bipolar disorder (BP) in different ethnic
      groups in recent genome-wide association studies. The current study aimed to
      evaluate the associations of several Cav genes and subtypes of BP in genetically
      more homogeneous Taiwanese samples. Additionally, we tested interaction effects
      among genes that encode for alpha1, beta and gamma-subunits of calcium channel.
      METHODS: 8 Cav genes were selected based on evidence in prior association studies
      and significant linkage regions for BP. 280 BP patients and 200 controls were
      recruited. Multifactor dimensionality reduction was performed for interaction
      testing in these discovery samples. Replication was conducted for two markers
      using additional 495 Taiwanese cases and 1341 controls. RESULTS: Weak
      associations for CACNA1C (rs10848635), CACNA1E (rs10848635), CACNB2 (rs11013860),
      and CACNG2 (rs2284018) genes were observed. Joint analysis of four markers
      revealed higher accumulative risk with increasing numbers of risk genotypes an
      individual endorsed for BP-I (Ptrend=0.006) and BP-II (Ptrend=0.017) disorders.
      Combined analysis with independent replication samples further supported the
      association of rs11013860 in CACNB2 with BP subtype I (P=1*10(-6)). Suggestive
      interactions were found between genes encoded for different subunits of calcium
      channel (alpha1, beta, and gamma). LIMITATIONS: Moderate sample size and
      incomplete markers coverage for the chosen Cav genes. CONCLUSIONS: Our results
      support the involvement of different calcium channel genes in bipolar illness, in
      particular the beta-subunit in the Asian population. Further investigation of
      functional property of these genes can contribute on understanding the
      etiological mechanisms of bipolar illness.

PMID- 24581831
TI  - Age at onset of recurrent major depression in Han Chinese women - a replication
      study.
AB  - BACKGROUND: The relationship between age at onset (AAO) and major depression (MD)
      has been studied in US, European and Chinese populations. However, larger sample
      studies are needed to replicate and extend earlier findings. METHODS: We re
      examined the relationship between AAO and the clinical features of recurrent MD
      in Han Chinese women by analyzing the phase I (N=1848), phase II (N=4169) and
      total combined data (N=6017) from the CONVERGE project. Linear, logistic,
      multiple linear and multinomial logistic regression models were used to determine
      the association of AAO with continuous, binary and categorical variables.
      RESULTS: The effect size of the association between AAO and clinical features of
      MD was quite similar in the phase I and phase II samples. These results confirmed
      that MD patients with earlier AAO tended to suffer more severe, recurrent and
      chronic illness and cases of MD with earlier AAO showed increased neuroticism,
      greater family history and psychiatric comorbidity. In addition, we showed that
      earlier AAO of MD in Han Chinese women was associated with premenstrual symptoms,
      postnatal depression, a highly authoritarian or cold childhood parental rearing
      style and a reduced probability for having melancholia. LIMITATIONS: Data were
      collected retrospectively through interview and recall bias may have affected the
      results. CONCLUSIONS: MD with earlier AAO in Han Chinese women shows a distinct
      set of clinical features which are similar to those reported in Western
      populations.

PMID- 24581836
TI  - Isolated right atrial infarction from occluded non-dominant right coronary
      artery.

PMID- 24581835
TI  - Cry1 and Tef gene polymorphisms are associated with major depressive disorder in
      the Chinese population.
AB  - INTRODUCTION: Accumulating evidences indicate that circadian abnormalities lead
      to sleep disorder, neurodegenerative diseases and depression. We have reported
      that the polymorphisms of a clock-related gene, Tef, contributed to the risk of
      sleep disturbances and depression in the Parkinson disease. The objective of the
      present study was to examine whether the three clock genes we previously studied
      are associated with major depressive disorder (MDD) in the Chinese population.
      METHODS: 105 Subjects with MDD and 485 control subjects participated in this case
      control study. Demographics, Mini-mental Status Examination (MMSE), and the
      Hamilton rating scale for depression (HAMD) were obtained in all subjects.
      Genotypes of single nucleotide polymorphisms (SNPs) of Cry1 rs2287161, Cry2
      rs10838524 and Tef rs738499 were screened by polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP). RESULTS: MDD cases had a
      significantly higher frequency carrying the C allele and CC genotype in Cry1
      rs2287161 and the T allele and TT genotype in Tef rs738499 than controls.
      LIMITATIONS: The sample size of MDD group was relatively small. CONCLUSIONS: The
      polymorphisms of Cry1 rs2287161 and Tef rs738499 are associated to MDD.

PMID- 24581834
TI  - The prevalence, clinical correlates and structure of phobic fears in Han Chinese
      women with recurrent major depression.
AB  - BACKGROUND: Phobic fears are common in the general population and among
      individuals with major depression (MD). We know little about the prevalence,
      clinical correlates, and structure of phobic fears in Chinese women with MD.
      METHODS: We assessed 22 phobic fears in 6017 Han Chinese women with MD. We used
      exploratory factor analysis to examine the structure of these phobic fears. We
      examined the relationship between individual phobic fears and the severity of MD,
      neuroticism, comorbid panic disorder, generalized anxiety disorder and dysthymia
      using logistic regression models. RESULTS: The frequency of phobic fears ranged
      from 3.0% (eating in public) to 36.0% (snakes). Phobic fears were significantly
      associated with more severe MD, high neuroticism, and co-morbid panic disorder,
      generalized anxiety disorder and dysthymia. Our factor analysis suggested four
      underlying subgroups of phobic fears which differed in their clinical correlates,
      severity and patterns of comorbidity. LIMITATIONS: Data were collected
      retrospectively through interview and recall bias may have affected the results.
      CONCLUSIONS: Phobic fears are correlated with comorbid MD and more severe MD.
      These phobic fears clearly subdivide into four subgroups that differ meaningfully
      from each other.

PMID- 24581837
TI  - Production of a biodegradable plastic-degrading enzyme from cheese whey by the
      phyllosphere yeast Pseudozyma antarctica GB-4(1)W.
AB  - Cheese whey is a by-product of cheese production and has high concentrations of
      lactose (about 5%) and other nutrients. Pseudozyma antarctica produces a unique
      cutinase-like enzyme, named PaE, that efficiently degrades biodegradable
      plastics. A previous study showed that a combination of 1% oil and 0.5% lactose
      increased cutinase-like enzyme production by another species of yeast. In this
      study, to produce PaE from cheese whey, we investigated the effects of soybean
      oil on PaE production (expressed as biodegradable plastic-degrading activity) by
      P. antarctica growing on lactose or cheese whey. In flask cultures, the final PaE
      activity was only 0.03 U/ml when soybean oil was used as the sole carbon source,
      but increased to 1.79 U/ml when a limited amount of soybean oil (under 0.5%) was
      combined with a relatively high concentration of lactose (6%). Using a 5-L jar
      fermentor with lactose fed-batch cultivation and periodic soybean oil addition,
      about 14.6 U/ml of PaE was obtained after 5 days of cultivation. When the lactose
      was replaced with cheese whey, PaE production was 10.8 U/ml after 3 days of
      cultivation.

PMID- 24581838
TI  - [Early diagnosis of peripheral arteriopathy through the automated determination
      of the ankel-arm index].

PMID- 24581839
TI  - [Guillain-Barre syndrome mimicking encephalic death].

PMID- 24581840
TI  - [The quadrivalent vaccines against seasonal influenza. Are the ultimate
      solution?].

PMID- 24581841
TI  - [Health related quality of life in the kidney transplant patient].

PMID- 24581842
TI  - [Breast plasmocytoma in a male patient].

PMID- 24581843
TI  - [Discrepancy regarding the use of cranioplasty with bandaging as a form of
      limitation of life support treatment. Another point of view].

PMID- 24581844
TI  - Novel insertion mutation in the PVRL1 gene in Turkish patients with non-syndromic
      cleft lip with/without cleft palate.
AB  - OBJECTIVES: Non-syndromic cleft lip with/without cleft palate (nsCL/P) has a
      complex aetiology involving both genetic and environmental factors. The aim of
      this study was to investigate the association between PVRL1 gene mutations and
      Turkish patients with nsCL/P. DESIGN: In this study, 80 Turkish patients with
      nsCL/P and 125 unrealeted individuals were analyzed. Mutations were detected
      using polymerase chain reactions and DNA sequencing. RESULTS: We found a novel
      GGA insertion between nucleotide positions c.1311_1313delGGA in exon 6 of the
      PVRL1 gene. Fifteen of the 80 patients with nsCL/P had the GGA insertion,
      although no mutation was found in the 125 unrelated individuals. CONCLUSION: We
      identified new supportive evidence that the association between PVRL1 gene and
      nsCL/P.

PMID- 24581845
TI  - Histometric evaluation of dental alveolar repair in malnourished rats in the
      intrauterine or postnatal phase.
AB  - OBJECTIVE: Nutritional aggravations during pregnancy or during the early stages
      of postnatal development can impair bone development; thus, we aimed to assess
      the effects of food restriction on the dental alveolar bone repair process using
      histometric analysis. DESIGN: Thirty-six Wistar rats were divided into three
      groups: (C) 12 pups were obtained from control mothers with food intake at ease;
      (GR) 12 pups from mothers subjected to 70% food restriction during pregnancy;
      (PNR) 50% of maternal food restriction during lactation and 50% of restriction
      for the 12 pups after weaning. At three months of age, the upper right incisor
      was extracted from the pups. After 14 or 28 days, the pups were sacrificed for
      evaluation of newly formed bone area (NB) and total bone area (TA) in the medial
      and apical thirds of the alveolus. RESULTS: In the apical third of the alveolus,
      the ratio of NB/TA was greater at 28 days for all groups and there was no damage
      to any of the groups. In the medial third, the ratio was higher at 28 days for
      the C and GR groups. The PNR group did not show an evolution of alveolar dental
      repair. Compared between the thirds, all groups exhibited a higher percentage of
      newly formed bone in the medial third area, at any time point after surgery.
      CONCLUSIONS: The percentage of the total alveolar area covered by newly formed
      bone (NB/TA) revealed a late preference in the process of alveolar repair in the
      medial third, although only in the PNR group.

PMID- 24581846
TI  - Peripheral GABAA receptor activation modulates rat tongue afferent mechanical
      sensitivity.
AB  - OBJECTIVES: The expression of GABA(A) receptors and the effects of GABAA receptor
      agonists on the response properties of tongue afferent fibres were investigated
      in female rats to determine if peripheral GABA receptors might be a target of
      topical benzodiazepines when used for pain relief in burning mouth syndrome
      patients. DESIGN: Nerve fibres in tongue sections from six female rats were
      identified using protein gene product 9.5, and the co-expression of the gamma
      subunit of GABAA receptor and substance P assessed in the nerve fibres. In vivo
      extracellular recordings of trigeminal ganglion neurons that innervate the tongue
      were undertaken in 27 anesthetised female rats and their responses to mechanical
      and thermal stimulation characterised before and after topical application of
      GABA, the GABA(A) receptor selective agonist muscimol or vehicle control.
      RESULTS: The vast majority of tongue nerve fibres examined (95%) expressed the
      gamma subunit of GABA(A) receptor. Bath application of muscimol, but not GABA,
      significantly increased the mechanical thresholds of tongue afferent fibres
      compared to vehicle, but only after the tongue had been heated with 60 degrees C
      water. CONCLUSIONS: GABA(A) receptors are present on tongue nerve fibres and
      their activation alters the mechanical sensitivity these fibres. These findings
      suggest that topical application of benzodiazepines to the oral mucosa may
      decrease pain in burning mouth syndrome through a local action on peripheral
      GABAA receptors.

PMID- 24581847
TI  - Long-term curcumin treatment antagonizes masseter muscle alterations induced by
      chronic unpredictable mild stress in rats.
AB  - OBJECTIVE: To investigate the correlation between psychological stress and
      masseter muscle (MM) alterations, and explore the therapeutic agents for
      restoring the impaired masticatory muscle. DESIGN: We established a chronic
      unpredictable mild stress (CUMS) animal model and observed the changes of
      ultrastructure, redox homeostasis and energy metabolism in MM in rats with and
      without curcumin treatment. RESULTS: The depressive-like behavior in stressed
      rats was confirmed by the evidences of altered behaviors in sucrose preference
      test and open field test; while these phenomena were eased by curcumin. Except
      for the pathological changes in ultrastructure, decreased SOD, GSH-Px, CAT, Na(+)
      K(+)ATPase, and Ca(2+)-Mg(2+)ATPase activities as well as increased MDA and LD
      content and LDH activity were also observed in MM in stressed rats. However,
      curcumin was capable of reversing CUMS-induced MM disorder by improving the
      activities of the examined anti-oxidant enzymes and energy metabolism enzymes.
      Additionally, the increased MDA content, LD content, and LDH activity in stressed
      rats were reduced by curcumin. CONCLUSION: All the findings indicate the adverse
      effects of CUMS on MM function in rats, and raise the possibility of developing
      curcumin as a potential therapeutic agent for psychological stress-induced
      masseter dysfunction.

PMID- 24581848
TI  - Bone marrow mesenchymal stem cells stimulated by bFGF up-regulated protein
      expression in comparison with periodontal fibroblasts in vitro.
AB  - OBJECTIVE: The aim of this study was to evaluate, in vitro, the role of bFGF in
      the proliferation and expression of collagen type I and fibronectin of dog bone
      marrow mesenchymal stem cells (dBMMSCs) in comparison with the expression of the
      same proteins in dog periodontal fibroblasts (dPLFs). DESIGN: dBMMSCs from the
      iliac crest were cultivated in Dulbecco's Modified Eagle's Medium (DMEM). Flow
      cytometry analysis (FCA) was used to characterize dBMMSC. Cells were stimulated
      with bFGF (1, 5 and 10 ng/mL) after 24 and 48 h. Real time RT-PCR was performed
      to verify collagen type I and fibronectin expressions. MTT assay was used to
      confirm cellular proliferation. Statistical analyses were performed (ANOVA and
      Kruskal-Wallis tests; p<0.05). RESULTS: FCA showed 55.98% of CD34+ and 32.67% of
      CD90+ after bone marrow aspiration; 3.33% of CD34+ and 33.0% of CD90+ before P1.
      After P2, 10.54% of dBMMSCs expressed CD90, whereas after P3, this number
      decreased to 1.58%. dPLFs presented 4.04% of CD90+ and 1.05% of CD34+ after P3.
      MTT evaluation showed increase in dBMSC proliferation with 5 ng/mL bFGF-stimulus
      after 24-h. Both collagen I and fibronectin expression were very similar between
      the two cells groups after 24-h stimulation with 1 ng/mL bFGF concentration.
      Fibronectin and collagen I expressions were higher after 24-h stimulation with 5
      ng/mL bFGF. CONCLUSION: dBMMSCs (1 ng/mL-bFGF stimulus after 24 h) are very
      similar to dPLFs as regards morphological and immunostaining characteristics, and
      collagen and/or fibronectin production. The dBMMSCs presented the highest protein
      expression rates with 5 ng/mL-bFGF stimulus after 24-h.

PMID- 24581849
TI  - The CPP-ACP relieved enamel erosion from a carbonated soft beverage: an in vitro
      AFM and XRD study.
AB  - OBJECTIVES: To investigate the CPP-ACP's effect on enamel against carbonated
      beverage erosion and explore the potential mechanism. METHODS: A total of 30
      enamel samples were prepared from sound bovine incisors, divided into 3 groups.
      Samples in the control group were kept in artificial saliva. Specimens' surfaces
      were smeared with a CPP-ACP agent (Tooth Mousse, TM) for 3 min, rinsed with
      distilled water for 10s, merged into cola (Coca Cola, CC) for 4 intervals of 2
      min, rinsed again for the TM+CC group. In the CC group, specimens were treated
      solely with cola for 4 intervals (2 min each). The cycles were applied at 0, 12,
      24, 36, 48 and 60 h. The surface microhardness (SMH) alterations were measured
      using a microhardness tester, the surface profiles were analyzed using the atomic
      force microscope, and the surface crystalline amount (I%) and crystallinity
      (FWHM) were analyzed using X-ray diffractometer. RESULTS: The SMH were
      significantly decreased in CC group, showing the largest SMH alteration; the
      reduction of SMH in TM+CC group was lower than that in CC group, still larger
      than control. After cycles, the TM+CC group showed rougher surfaces than control,
      while the CC group had the roughest surfaces. The TM+CC had an I% higher than the
      CC, and lower than the control. The TM+CC group had a FWHM lower than CC, higher
      than control. CONCLUSIONS: CPP-ACP was able to relieve the erosion on enamel from
      carbonated beverage.

PMID- 24581850
TI  - Alpha 2 integrin gene (ITGA2) polymorphism in renal transplant recipients with
      and without drug induced gingival overgrowth.
AB  - BACKGROUND: Variances in fibroblasts' alpha2beta1 integrin intensity may lead to
      altered adhesion to type I collagen and consequently to suppression of
      phagocytosis which may be one of the mechanisms for drug induced gingival
      overgrowth. The present study aimed to evaluate the genotype and allele
      frequencies of alpha2 integrin +807 gene in renal transplant patients with and
      without gingival overgrowth. MATERIAL AND METHODS: Seventy renal transplant
      patients with cyclosporine A (CsA)-induced gingival overgrowth (CsA GO+) were
      enrolled. Renal transplant patients without GO medicated with CsA (CsA GO-; n=79)
      and tacrolimus (Tac; n=52) served as controls. DNA was obtained from peripheral
      blood and ITGA2 +807C/T polymorphism was genotyped by polymerase chain reaction
      and restriction fragment length polymorphism method. Clinical parameters
      including probing depth and plaque, papilla bleeding and hyperplasia indexes were
      recorded. Chi-square, Kruskal-Wallis and Mann-Whitney tests were used in
      statistical analysis. RESULTS: Clinical parameters of CsA GO+ group were
      significantly higher than those of the CsA GO- and Tac groups (p<0.05). ITGA2
      807C/T genotype and allele frequencies of study groups were similar (p>0.05).
      CONCLUSION: Within the limits of the present study it can be concluded that ITGA2
      +807 gene polymorphism is not associated with susceptibility to CsA-induced GO.

PMID- 24581851
TI  - Endothelin-1 induces interleukin-18 expression in human osteoblasts.
AB  - OBJECTIVE: Both endothelin-1 (ET-1) and interleukin (IL)-18 induce osteoblast
      proliferation under normal and pathophysiological conditions. In the present
      study, we explored the interaction between the two proteins by examining the
      effect of ET-1 on IL-18 expression in cultured human osteoblasts. METHODS: Human
      osteoblasts were treated with ET-1 in different concentrations (1, 10, 20, 40, or
      50 nM) for different length of time (1, 6, 12, 18, or 24 h) in the presence or
      absence of ET A receptor (ETAR) blocker BQ123, ET B receptor (ETBR) blocker
      BQ788, p38 mitogen-activated protein kinase (MAPK) siRNA, or different kinase
      inhibitors. RESULTS: ET-1 increased the IL-18 mRNA level in a statistically
      significant dose- and time-dependent manner within 18 h, which was reflected in
      dose-dependent induction of the human IL-18 gene promoter activity and IL-18
      protein/secreted protein expression. BQ123 (1MU M) and p38 MAPK siRNA and
      inhibitor PD169316 (25 MUM) completely abolished the promoting effect of ET-1 on
      IL-18 expression. [(3)H]thymidine incorporation assays showed that ET-1 lost a
      major part (57%) of its promoting effect on osteoblast proliferation when the
      endogenous IL-18 expression in osteoblasts was knocked down by 75%. CONCLUSIONS:
      ET-1 induces IL-18 expression in human osteoblasts at the gene
      promoter/transcription level via ETAR by a p38 MAPK-dependent mechanism, and that
      IL-18 mediates a major part of ET-1 induced osteoblast proliferation. This study
      provides the first evidence of interaction between ET-1 and IL-18 in osteoblast
      and adds new insights into bone physiology and pathophysiology.

PMID- 24581852
TI  - Radicular grooves of maxillary anterior teeth in a Turkish population: a cone
      beam computed tomographic study.
AB  - OBJECTIVE: There is limited data on the use of cone-beam computed tomography
      (CBCT) scanning in examining radicular groove (RG). This study aims to
      investigate the presence of RG in maxillary anterior teeth in a Turkish
      Population using CBCT scanning and to correlate the findings with the tooth type,
      and patient's gender. DESIGN: A total of 1969 CBCT images of maxillary anterior
      teeth obtained from 342 patients were included in the study. Patients' age and
      gender, the tooth type (central/lateral incisor, canine), and the
      presence/absence, bilateral/unilateral diversity, and type of RG were recorded.
      The RG type was categorized using Gu's classification. Statistical analysis was
      carried out to correlate the findings with tooth type, and gender using the
      chi(2) test (p=0.05). RESULTS: RGs were detected in 4 (0.6%) central incisors, 15
      (2.3%) lateral incisors, and 0 canines. The frequency of RGs in males was higher
      than in females. There were statistically significant differences among the
      different tooth types in terms of the presence of RGs (p<0.001). Statistical
      analysis also revealed a significant difference between the males and females in
      terms of the presence of RGs (p=0.003). CONCLUSIONS: The prevalence of RGs was
      statistically higher in males than in females and in lateral incisors compared to
      central incisors. CBCT may be recommended as an effective diagnostic device to
      identify RGs.

PMID- 24581853
TI  - Isolation, biochemical characterization and anti-bacterial activity of BPIFA2
      protein.
AB  - OBJECTIVE: Human BPIFA2 (parotid secretory protein) is a ubiquitous soluble
      salivary protein, which belongs to the PLUNC family of proteins. Having sequence
      similarity to bactericidal/permeability-increasing protein and lipopolysaccharide
      binding protein, PLUNC proteins are probably involved in local antibacterial
      response at mucosal sites, such as oral cavity. The aim of the study was to
      isolate and characterize human BPIFA2. DESIGN: In this paper, we report one-step
      affinity chromatography method for BPIFA2 purification from whole human saliva.
      The isolated BPIFA2 was identified by trypsin mass fingerprinting and
      characterized by electrophoretic methods. Antibacterial activity of BPIFA2
      against model microorganism Pseudomonas aeruginosa was shown in minimum
      inhibitory concentration and time kill study assays. RESULTS: The protein showed
      microheterogeneity, both in molecular weight and pI value. BPIFA2 inhibited the
      growth of P. aeruginosa in microgram concentration range determined by minimum
      inhibitory concentration assay. In the time kill study, 32MUg/mL BPIFA2 showed
      clear bactericidal activity and did not cause any aggregation of bacteria.
      CONCLUSION: Affinity chromatography is well suited for isolation of functional
      BPIFA2 with a potent bactericidal activity against P. aeruginosa.

PMID- 24581854
TI  - Three-dimensional spheroid culture promotes odonto/osteoblastic differentiation
      of dental pulp cells.
AB  - OBJECTIVE: Three-dimensional (3D) spheroid culture is a method for creating 3D
      aggregations of cells and their extracellular matrix without a scaffold mimicking
      the actual tissues. The aim of this study was to evaluate the effects of 3D
      spheroid culture on the phenotype of immortalized mouse dental papilla cells
      (MDPs) that have the ability to differentiate into odontoblasts. METHODS: We
      cultured MDPs for 1, 3, 7, and 14 days in 96-well low-attachment culture plates
      for 3D spheroid culture or flat-bottomed plates for two-dimensional (2D)
      monolayer culture. Cell proliferation and apoptosis were detected by
      immunohistochemical staining of Ki67 and cleaved caspase-3, respectively. Hypoxia
      was measured by the hypoxia probe LOX-1. Odonto/osteoblastic differentiation
      marker gene expression was evaluated by quantitative PCR. We also determined
      mineralized nodule formation, alkaline phosphatase (ALP) activity, and dentine
      matrix protein-1 (DMP1) expression. Vinculin and integrin signalling-related
      proteins were detected immunohistochemically. RESULTS: Odonto/osteoblastic marker
      gene expression and mineralized nodule formation were significantly up-regulated
      in 3D spheroid-cultured MDPs compared with those in 2D monolayer-cultured MDPs
      (p<0.05). Histologically, 3D spheroid colonies consisted of two compartments: a
      cell-dense peripheral zone and cell-sparse core zone. Proliferating cells with
      high ALP activity and DMP1 expression were found mainly in the peripheral zone
      that also showed strong expression of vinculin and integrin signalling-related
      proteins. In contrast, apoptotic and hypoxic cells were detected in the core
      zone. CONCLUSION: 3D spheroid culture promotes odonto/osteoblastic
      differentiation of MDPs, which may be mediated by integrin signalling.

PMID- 24581855
TI  - The effect of delmopinol and fluoride on acid adaptation and acid production in
      dental plaque biofilms.
AB  - OBJECTIVE: To investigate the effect of delmopinol and fluoride alone or in
      combination on acid adaptation and acid production in plaque biofilm bacteria in
      vitro. DESIGN: The effect of delmopinol and fluoride on acid adaptation was
      tested by exposing the biofilm bacteria, grown in a mini-flow cell system under
      static conditions, to pH 5.5 overnight in the presence of 0.16 mM delmopinol, 1
      mF NaF or a combination of both. The following day, acid adaptation was evaluated
      by exposing the cells to an acid challenge for 2h at a pH known to kill non
      adapted cells (pH 2.5). The cells were stained using LIVE/DEAD BacLight Viability
      stain and the number of viable (acid tolerant) cells was determined using
      confocal scanning laser microscopy. Control cells were treated in the same manner
      but without the exposure to delmopinol or fluoride. How delmopinol and fluoride
      affected acid production was assessed by measuring the pH-drop after glucose
      pulsing in the presence of delmopinol and/or different concentrations of
      fluoride. RESULTS: Fluoride alone or in combination with delmopinol affected the
      acid adaptation and significantly reduced the acid tolerance of the plaque
      biofilm. This effect was more pronounced when the two compounds were combined.
      Delmopinol alone did not affect acid adaptation. A combination of delmopinol and
      fluoride also reduced acid production at concentrations where neither of the
      compounds in isolation had an effect. CONCLUSION: Fluoride and delmopinol can
      work synergistically to affect acid adaptation and acid production in plaque
      biofilm bacteria.

PMID- 24581856
TI  - Applied anatomy of the lingual nerve: relevance to dental anaesthesia.
AB  - OBJECTIVES: (1) to classify the external morphology of the lingual nerve and
      investigate any relationship between its external and internal morphology, (2) to
      explore the fascicular structure, nerve tissue density and capillary density of
      the lingual nerve, and (3) to provide an anatomical explanation as to why adverse
      clinical outcomes more commonly affect the lingual nerve following local dental
      anaesthesia. Where possible, comparisons were made between the lingual and
      inferior alveolar nerves. MATERIALS AND METHODS: The lingual and inferior
      alveolar nerves were examined in 23 hemi-sectioned heads macroscopically and
      microscopically 2mm above the lingula. The lingual nerve was also examined in the
      regions of the third and second molars. Specimens underwent histological
      processing and staining with Haematoxylin & Eosin, Masson's Trichrome, anti-GLUT
      1 and anti-CD 34. RESULTS: The lingual nerve became flatter as it traversed
      through the pterygomandibular space. There was an increase in the connective
      tissue and a decrease in nerve tissue density along the lingual nerve (p<0.001).
      At 2mm above the lingula, the lingual nerve was uni-fascicular in 39% of cases,
      whilst the inferior alveolar nerve consistently had more fascicles (p<0.001). The
      lingual nerve fascicles had thicker perineurium but the endoneurial vascular
      density was not significantly different in the two nerves. CONCLUSIONS: The
      greater susceptibility of lingual nerve dysfunction during inferior alveolar
      nerve blocks may be due to its uni-fascicular structure and the thicker
      perineurium, leading to increased endoneurial pressure and involvement of all
      axons if oedema or haemorrhage occurs due to trauma.

PMID- 24581857
TI  - Effect of fluoride gels supplemented with sodium trimetaphosphate on enamel
      erosion and abrasion: in vitro study.
AB  - OBJECTIVE: This in vitro study aims to evaluate the effect of low fluoride (F)
      gel associate sodium trimetaphosphate (TMP) on erosion with or without abrasion.
      DESIGN: Enamel blocks (4 mm * 4 mm) selected through surface hardness (SH) is
      divided into five groups (n=12): gel without F and TMP (placebo), gel containing
      4500 ppm F (4500), gel containing 4500 ppm F plus TMP5% (4500 TMP5%), gel
      containing 9000 ppm F (9000), and gel containing 12,300 ppm F (acid gel). Those
      groups were additionally subdivided into conditions of erosion (Ero) and of
      erosion plus abrasion (Ero/Abra). The blocks have undergone a single application
      of gel on the first day of the study. The erosion challenge was produced by
      Sprite Zero for five minutes four times a day and abrasion was carried out by
      machine brushing for 15s. After the challenges, the surface hardness (%SH), wear
      and cross-sectional hardness (DeltaKHN) were analyzed. The data were analyzed
      using a 2-way ANOVA test followed by a Student-Newman-Keuls (p<0.05). RESULTS:
      Lower values of %SH, wear and DeltaKHN were observed for erosion challenge
      (p<0.001). The %SH was lower in groups treated with fluoride gels, differing in
      the placebo (p<0.05). With addition of TMP to the gel 4500, enamel wear was lower
      when compared with another groups (p<0.05). CONCLUSION: In vitro conditions, the
      4500 5%TMP gel showed greatest effect against erosion and erosion/abrasion.

PMID- 24581858
TI  - The influence of retraction agents on cytoskeleton reorganization and oxidative
      stress in primary human gingival fibroblasts (HGFs).
AB  - OBJECTIVE: Contemporary gingival retraction chemicals are not without
      disagreeable side-effects; there appears to be no best gingival retraction agent.
      The aim of this research was to select the most biocompatible retraction agents
      based on examination of the parameters of oxidative stress in fibroblasts derived
      from human primary cell culture. DESIGN: In this in vitro study we evaluated
      parameters of oxidative stress after treatment with retraction agents. Visine,
      Afrin, Neosynephrin, Strazolin and Adrenaline were the commercial products
      studied as gingival retraction agents. Additionally we examined three
      experimental agents. We determined lipid peroxidation and protein damage and
      monitored changes in cellular cytoskeleton proteins. Proliferative and survival
      efficiency were also evaluated. RESULTS: Oxidative changes included by evaluated
      retraction agents were at the lowest level in the case of the experimental gels.
      Also cytoskeleton observations suggest that the experimental agents did not
      degrade the cellular structure of human gingival fibroblasts (HGFs). CONCLUSIONS:
      The current study was performed because of a need to project new nontoxic and
      save retraction agents for peridontological therapeutic usage. We suggest that
      the new investigational gels are most biocompatible with periodontal tissues and
      can be applied as new vasoconstrictor chemical retraction agents.

PMID- 24581859
TI  - Novel missense mutations in the AXIN2 gene associated with non-syndromic
      oligodontia.
AB  - OBJECTIVE: Oligodontia, which is the congenital absence of six or more permanent
      teeth excluding third molars, may contribute to masticatory dysfunction, speech
      alteration, aesthetic problems and malocclusion. To date, mutations in EDA,
      AXIN2, MSX1, PAX9, WNT10A, EDAR, EDARADD, NEMO and KRT 17 are known to associate
      with non-syndromic oligodontia. The aim of the study was to search for AXIN2
      mutations in 96 patients with non-syndromic oligodontia. DESIGN: We performed
      mutation analysis of 10 exons of the AXIN2 gene in 96 patients with isolated non
      syndromic oligodontia. RESULTS: We identified two novel missense mutations (Exon
      3 c.923C>T and Exon 11 c.2490G>C) in two patients. One mutation (c.923C>T)
      results in a Thr308Met substitution and the other mutation (c.2490G>C) results in
      a Met830Ile substitution. CONCLUSIONS: This is the first report indicating that
      mutations in AXIN2 are responsible for oligodontia in the Chinese population. Our
      findings indicate that AXIN2 can be regarded as a candidate gene for mutation
      detection in individuals with non-syndromic oligodontia in the Chinese
      population.

PMID- 24581860
TI  - Gene expression based evidence of innate immune response activation in the
      epithelium with oral lichen planus.
AB  - OBJECTIVE: Oral lichen planus (OLP) is a disease of the oral mucosa of unknown
      cause producing lesions with an intense band-like inflammatory infiltrate of T
      cells to the subepithelium and keratinocyte cell death. We performed gene
      expression analysis of the oral epithelium of lesions in subjects with OLP and
      its sister disease, oral lichenoid reaction (OLR), in order to better understand
      the role of the keratinocytes in these diseases. DESIGN: Fourteen patients with
      OLP or OLR were included in the study, along with a control group of 23 subjects
      with a variety of oral diseases and a normal group of 17 subjects with no
      clinically visible mucosal abnormalities. Various proteins have been associated
      with OLP, based on detection of secreted proteins or changes in RNA levels in
      tissue samples consisting of epithelium, stroma, and immune cells. The mRNA level
      of twelve of these genes expressed in the epithelium was tested in the three
      groups. RESULTS: Four genes showed increased expression in the epithelium of OLP
      patients: CD14, CXCL1, IL8, and TLR1, and at least two of these proteins, TLR1
      and CXCL1, were expressed at substantial levels in oral keratinocytes.
      CONCLUSIONS: Because of the large accumulation of T cells in lesions of OLP it
      has long been thought to be an adaptive immunity malfunction. We provide evidence
      that there is increased expression of innate immune genes in the epithelium with
      this illness, suggesting a role for this process in the disease and a possible
      target for treatment.

PMID- 24581861
TI  - Menthol cigarettes and the cardiovascular risks of people living with HIV.
AB  - The possibility that menthol cigarettes add to the deleterious cardiovascular
      effects of smoking has been barely discussed. Although cardiovascular diseases
      (CVD) are at the forefront of medical concerns of people living with HIV (PLWH),
      an important, yet unknown, issue for clinicians and public health authorities is
      whether use of menthol-flavored cigarettes heightens CVD risk factors. Our study
      aims to assess traditional (10-year risk using the Framingham Risk Model) and
      nontraditional CVD risk factors and to contrast the effects of menthol-flavored
      versus non-menthol-flavored cigarettes on these risk factors. Compared to
      controls, menthol smokers were twice as likely to have hypertension. Users of
      menthol-flavored cigarettes had higher body mass index values, and increased risk
      of abdominal obesity. Multivariate analyses indicated that menthol smokers
      doubled the odds of having moderate to high CVD risk. This finding is highly
      significant given the widespread use of menthol-flavored cigarettes, particularly
      among women, minorities, and PLWH. 

PMID- 24581862
TI  - Fixed-bed biosorption of cadmium using immobilized Scenedesmus obliquus CNW-N
      cells on loofa (Luffa cylindrica) sponge.
AB  - A continuous fixed-bed biosorption process was established for cadmium (Cd)
      removal by Scenedesmus obliquus CNW-N (isolated from southern Taiwan) cells
      immobilized onto loofa sponge. This immobilized-cell biosorption process allows
      better recovery and reusability of the microalgal biomass. The growth of
      microalgae on the matrix support with appropriate nutrient supplementation could
      enhance the overall metal removal activity. Major operating parameters (e.g.,
      feeding flow rate, cycle number of medium replacement, and particle diameter of
      the sponge) were studied for treatability evaluation. The most promising cell
      growth on the sponge support was obtained at a flow rate of 0.284 bed volume
      (BV)/min, sponge particle diameter of 1 cm, and with one cycle of medium
      replacement. The performance of fixed-bed biosorption (adsorption capacity of
      38.4 mg, breakthrough time at 15.5 h) was achieved at a flow rate of 5 ml/min
      with an influent concentration of 7.5 mg Cd/l.

PMID- 24581863
TI  - Recovery of high-value metals from geothermal sites by biosorption and
      bioaccumulation.
AB  - Generation of geothermal energy is associated with a significant amount of
      geothermal fluids, which may be abundant in high-value metals, such as lithium,
      cesium, rubidium, and other precious and rare earth metals. The recovery of high
      value metals from geothermal fluids would thus have both economic and
      environmental benefits. The conventional technologies applied to achieve this are
      mostly physicochemical, which may be energy intensive, pose the risk of secondary
      pollution whilst being inefficient in recovering metals from dilute solutions.
      Biological methods, based on biosorption or bioaccumulation, have recently
      emerged as alternative approaches, as they are more environmentally friendly,
      cost effective, and suitable for treating wastewater with dilute metal contents.
      This article provides a comprehensive review of the related biological
      technologies used to recover the high-value metals present in geothermal fluids
      as well as critical discussion on the key issues that are often used to evaluate
      the effectiveness of those methods. 

PMID- 24581864
TI  - Xylanase and cellulase systems of Clostridium sp.: an insight on molecular
      approaches for strain improvement.
AB  - Bioethanol and biobutanol hold great promise as alternative biofuels, especially
      for transport sector, because they can be produced from lignocellulosic agro
      industrial residues. From techno-economic point of view, the bioprocess for
      biofuels production should involve minimal processing steps. Consolidated
      bioprocessing (CBP), which combines various processing steps such as
      pretreatment, hydrolysis and fermentation in a single bioreactor, could be of
      great relevance for the production of bioethanol and biobutanol or solvents
      (acetone, butanol, ethanol), employing clostridia. For CBP, Clostridium holds
      best promise because it possesses multi-enzyme system involving cellulosome and
      xylanosome, which comprise several enzymes such as cellulases and xylanases. The
      aim of this article was to review the recent developments on enzyme systems of
      clostridia, especially xylanase and cellulase with an effort to analyse the
      information available on molecular approaches for the improvement of strains with
      ultimate aim to improve the efficiencies of hydrolysis and fermentation.

PMID- 24581865
TI  - The added value of a portable gamma camera for intraoperative detection of
      sentinel lymph node in squamous cell carcinoma of the oral cavity: A case report.
AB  - The use of sentinel lymph node biopsy in squamous cell carcinoma of the oral
      cavity is still subject to debate although some studies have reported its
      feasibility. The main reason for this debate is probably due to the high false
      negative rate for floor-of-mouth tumors per se. We report the case of a 54-year
      old man with a T1N0 floor-of-mouth squamous cell carcinoma who underwent the
      sentinel lymph node procedure. Lymphoscintigraphy and SPECT/CT imaging were
      performed for lymphatic mapping with a conventional gamma camera. Sentinel lymph
      nodes were identified at right Ib, left IIa and Ia levels. However, these
      sentinel lymph nodes were difficult to detect intraoperatively with a gamma probe
      owing to the activity originating from the injection site. The use of a portable
      gamma camera made it possible to localize and excise all the sentinel lymph
      nodes. This case demonstrates the usefulness of this tool to improve sentinel
      lymph node detecting in floor-of-mouth tumors, especially those close to the
      injection area.

PMID- 24581866
TI  - Solid-state NMR/NQR and first-principles study of two niobium halide cluster
      compounds.
AB  - Two hexanuclear niobium halide cluster compounds with a [Nb6X12](2+) (X=Cl, Br)
      diamagnetic cluster core, have been studied by a combination of experimental
      solid-state NMR/NQR techniques and PAW/GIPAW calculations. For niobium sites the
      NMR parameters were determined by using variable Bo field static broadband NMR
      measurements and additional NQR measurements. It was found that they possess
      large positive chemical shifts, contrary to majority of niobium compounds studied
      so far by solid-state NMR, but in accordance with chemical shifts of (95)Mo
      nuclei in structurally related compounds containing [Mo6Br8](4+) cluster cores.
      Experimentally determined deltaiso((93)Nb) values are in the range from 2,400 to
      3,000 ppm. A detailed analysis of geometrical relations between computed electric
      field gradient (EFG) and chemical shift (CS) tensors with respect to structural
      features of cluster units was carried out. These tensors on niobium sites are
      almost axially symmetric with parallel orientation of the largest EFG and the
      smallest CS principal axes (Vzz and delta33) coinciding with the molecular four
      fold axis of the [Nb6X12](2+) unit. Bridging halogen sites are characterized by
      large asymmetry of EFG and CS tensors, the largest EFG principal axis (Vzz) is
      perpendicular to the X-Nb bonds, while intermediate EFG principal axis (Vyy) and
      the largest CS principal axis (delta11) are oriented in the radial direction with
      respect to the center of the cluster unit. For more symmetrical bromide compound
      the PAW predictions for EFG parameters are in better correspondence with the
      NMR/NQR measurements than in the less symmetrical chlorine compound.
      Theoretically predicted NMR parameters of bridging halogen sites were checked by
      (79/81)Br NQR and (35)Cl solid-state NMR measurements.

PMID- 24581867
TI  - Donor milk volume and characteristics of donors and their children.
AB  - BACKGROUND: Little is known regarding the effect of the characteristics of donors
      and their children on the volume of donor milk delivered to a human milk bank
      (HMB). AIMS: Our study aimed to determine the relationship between different
      social and demographic variables of donors and their infants with the volume of
      human milk delivered. METHODS: We included donors accepted at the Hospital Doce
      de Octubre HMB from January 1st, 2009 until April 31st, 2013, and who had
      finished their donation. Data of social and demographic characteristics of the
      donors and their children, and the total volume of DHM given were obtained from
      our HMB database. Included variables were previous donors, donor age, number of
      children, place of residence, gestational age of the infant at birth, child's age
      at the start of the donation, hospital admission, and death of the infant. A
      linear regression model was used to study the relationship between independent
      variables that were significant in bivariate analysis and the volume of donated
      milk. RESULTS: A total of 415 donations from 391 women were included. The median
      volume of milk delivered was 3.1l (IQR-interquartile range-1.3-8.3l). In the
      linear regression model, previous donors, smaller gestational age of children,
      and the start of donation at earlier stages of lactation were associated with a
      larger quantity of HMB donated (p<=0.001). CONCLUSION: Previous donors, smaller
      gestational age of children, and the start of donation at earlier stages of
      lactation are associated with a larger quantity of milk donated to the HMB.

PMID- 24581868
TI  - ["There are three sorts of people: those who are alive, those who are dead, and
      those who are at sea" (Aristotle): reply].

PMID- 24581869
TI  - A pseudo three-zone simulated moving bed with solvent gradient for quaternary
      separations.
AB  - In a SMB with solvent gradient, as the eluotropic strength of the liquid in zone
      II (between the extract-port and feed-port) is higher than that in zone III
      (between the feed-port and the raffinate-port), the solute can move forward in
      zone II but backward in zone III to be trapped in the two zones consequently. On
      this basis, a pseudo-SMB was proposed to separate two medium retained solutes (B1
      and B2) from a quaternary mixture by selectively trapping the two solutes. Once
      the columns in zones II and III are saturated with the target solutes, the
      solvent dissolving the feed is introduced at the feed-port to remove the least
      retained solute (A) from the raffinate-port and the most retained solute (C) from
      the extract-port. The two target components trapped in zones II and III are
      purified accordingly. At the same time, solute B1 would distribute in the columns
      of zone III whereas solute B2 spread in the columns of zone II if solute B2 had a
      stronger retention than solute B1. Thereby, the two medium retained solutes B1
      and B2 could be recovered separately from the columns in zones II and III. This
      scheme was validated by the successful separation of capsaicin (B1) and
      dihydrocapsaicin (B2) from a crude capsaicinoids. 

PMID- 24581870
TI  - Two novel extraction chromatography resins containing multiple diglycolamide
      functionalized ligands: preparation, characterization and actinide uptake
      properties.
AB  - Two extraction chromatography resins were prepared for the first time by
      impregnating multiple diglycolamide-functionalized ligands such as diglycolamide
      calix[4]arene (C4DGA) and tripodal diglycolamide (T-DGA) on Chromosorb-W, an
      inert solid support, for the removal of hazardous actinides like Am(III) from
      radioactive waste solutions at 3M nitric acid. The resins were characterized by
      SEM, thermal and surface area (BET) analyses. The sorption of Am(III) on the two
      resins followed pseudo-second order sorption rate kinetics and was exothermic in
      nature. The sorption of trivalent f-elements proceeded through a chemisorption
      monolayer phenomenon as analyzed by using several isotherm models. The negative
      free energy change (DeltaG) values of -34.46 and -28.45kJ/mol for T-DGA and
      C4DGA, respectively, indicate a chemical interaction between the metal ions and
      the ligands on the surface of the resins. Distribution coefficient measurements
      of various metal ions showed a selective sorption of trivalent f-elements over
      hexavalent uranyl ions and other fission product elements. Column studies on
      breakthrough indicated 0.76 and 0.37mg/g as the breakthrough capacities of the T
      DGA and the C4DGA resins, respectively. It was possible to quantitatively elute
      the loaded metal ion using EDTA solutions. 

PMID- 24581872
TI  - The elevated preoperative platelet to lymphocyte ratio predicts decreased time to
      recurrence in colon cancer patients.
AB  - BACKGROUND: Recent evidence indicates that tumor progression involves factors of
      systemic inflammation, such as platelets and lymphocytes. In this study, we
      investigated the prognostic relevance of the preoperative platelet to lymphocyte
      (P/L) ratio on time to recurrence (TTR) and overall survival (OS) in patients
      with stage II and III colon cancer (CC) who underwent curative resection.
      METHODS: In this retrospective study, 372 CC patients were included. Kaplan-Meier
      curves and multivariate Cox proportional models were calculated for TTR and OS.
      RESULTS: In univariate analysis, the elevated P/L ratio was significantly
      associated with decreased TTR (HR = 1.60, 95% CI = 1.02 to 2.51, P = .040) and
      remained significant in multivariate analysis (HR = 1.65, 95% CI = 1.05 to 2.58,
      P = .030), where HR and CI represent Hazard ratio and confidence interval,
      respectively. Patients with elevated P/L ratio showed a median TTR of 116 months.
      In contrast, patients with low P/L ratio had a median TTR of 132 months. In OS
      analysis, the elevated P/L ratio showed a trend toward decreased OS in univariate
      analysis (HR = 1.54, 95% CI = .95 to 2.48, P = .079). CONCLUSION: In this study,
      we identified the preoperative P/L ratio as a prognostic marker for TTR in stage
      II and III CC patients.

PMID- 24581871
TI  - GM1-gangliosidosis in American black bears: clinical, pathological, biochemical
      and molecular genetic characterization.
AB  - G(M1)-gangliosidosis is a rare progressive neurodegenerative disorder due to an
      autosomal recessively inherited deficiency of lysosomal beta-galactosidase. We
      have identified seven American black bears (Ursus americanus) found in the
      Northeast United States suffering from G(M1)-gangliosidosis. This report
      describes the clinical features, brain MRI, and morphologic, biochemical and
      molecular genetic findings in the affected bears. Brain lipids were compared with
      those in the brain of a G(M1)-mouse. The bears presented at ages 10-14 months in
      poor clinical condition, lethargic, tremulous and ataxic. They continued to
      decline and were humanely euthanized. The T(2)-weighted MR images of the brain of
      one bear disclosed white matter hyperintensity. Morphological studies of the
      brain from five of the bears revealed enlarged neurons with foamy cytoplasm
      containing granules. Axonal spheroids were present in white matter. Electron
      microscopic examination revealed lamellated membrane structures within neurons.
      Cytoplasmic vacuoles were found in the liver, kidneys and chondrocytes and foamy
      macrophages within the lungs. Acid beta-galactosidase activity in cultured skin
      fibroblasts was only 1-2% of control values. In the brain, ganglioside-bound
      sialic acid was increased more than 2-fold with G(M1)-ganglioside predominating.
      G(A1) content was also increased whereas cerebrosides and sulfatides were
      markedly decreased. The distribution of gangliosides was similar to that in the
      G(M1)-mouse brain, but the loss of myelin lipids was greater in the brain of the
      affected bear than in the brain of the G(M1) mouse. Isolated full-length cDNA of
      the black bear GLB1 gene revealed 86% homology to its human counterpart in
      nucleotide sequence and 82% in amino acid sequence. GLB1 cDNA from liver tissue
      of an affected bear contained a homozygous recessive T(1042) to C transition
      inducing a Tyr348 to His mutation (Y348H) within a highly conserved region of the
      GLB1 gene. The coincidence of several black bears with G(M1)-gangliosidosis in
      the same geographic area suggests increased frequency of a founder mutation in
      this animal population.

PMID- 24581873
TI  - Cotton-supported graphene functionalized with aminosilica nanoparticles as a
      versatile high-performance extraction sorbent for trace organic analysis.
AB  - Cotton fibers were functionalized, following the coating of fibers with graphene
      oxide (GO), the covalent attachment of aminosilica nanoparticles and the
      reduction to the cotton-GR-aminosilica material. Employing the cotton-supported
      graphene (GR)-aminosilica material, a novel and easily applicable extraction mode
      was put forward. Several groups of analytes were employed such as PAHs,
      phthalates, musks, phenolic endocrine disrupters and haloacetic acids to test the
      applicability of the functionalized cotton for extraction purposes. The
      extraction yields ranged from 76% to 96% corroborating the high degree of
      affinity of the material for the above groups of compounds while the limits of
      detection were between 0.06 and 1.10 MUg/L using gas chromatography-electron
      capture detection for haloacetic acids and gas chromatography-mass spectrometry
      for the rest of the analytes. The accuracy of the method was evaluated in
      fortified lake water at a spiking level of three to ten times the lowest
      quantifiable concentration and the recoveries varied from 86% to 104% for all the
      studied analytes. The pi-pi and hydrophobic interactions, the hydrogen bonding
      between the functionalized cotton and analytes and the electron polarizability
      and ionizability of the chemical structures justify the extraction behavior.

PMID- 24581874
TI  - The functional impact of bilateral reverse total shoulder arthroplasty.
AB  - BACKGROUND: The use of reverse total shoulder arthroplasty (RTSA) has been
      increasing. However, many recommend against bilateral RTSA because of concerns
      over lack of internal rotation (IR) and the resultant difficulties with
      activities of daily living (ADLs). METHODS: Data on 15 consecutive patients who
      underwent staged bilateral primary RTSA for cuff tear arthropathy (CTA) were
      retrospectively reviewed. All operations were performed by a single surgeon. The
      mean follow-up was 33.4 months from the second RTSA. The mean age of the patients
      at the time of the first operation was 72.9 years. The mean duration between
      arthroplasties was 21.6 months. Patients were evaluated preoperatively and
      postoperatively at 2 weeks, 6 weeks, 3 months, 6 months, 1 year, and yearly with
      standardized clinical examinations and outcome measures questionnaires. RESULTS:
      On both operative sides, elevation showed significant improvement from
      preoperative values; however, external rotation, abduction, and IR did not show
      significant improvement at an average follow-up of 33.4 months. Functional
      outcome scores of both RTSA shoulders showed significant improvement from
      preoperative values; however, the 12-Item Short-Form Health Survey scores on
      either shoulder did not show significant improvement. Evaluation of the outcome
      measures questionnaire revealed that all patients were able to perform perineal
      hygiene after their RTSAs. CONCLUSION: Bilateral RTSA results in marked
      improvement in forward elevation, pain, and functional outcomes, and carries a
      high rate of satisfaction in subjective patient assessment. Common ADLs that
      require significant IR, such as perineal care, were not problematic in the
      cohort.

PMID- 24581875
TI  - Use of three-dimensional fluoroscopy to determine intra-articular screw
      penetration in proximal humeral fracture model.
AB  - BACKGROUND: Proximal humeral locking plates have significantly improved the
      treatment of proximal humeral fractures in recent years; however, they are not
      devoid of complications. Inadvertent screw penetration into the joint is a well
      documented complication. Intraoperative 3-dimensional (3D) imaging may assist in
      detecting intra-articular implant penetration. This study compared the
      performance of a standard C-arm fluoroscope with a novel 3D imaging fluoroscope
      in detecting penetrating implants in a proximal humeral fracture model. METHODS:
      Zinc-sprayed proximal humerus sawbones were affixed with a proximal humeral
      locking plate. Six different constructs were assembled. In each specimen, 1
      screw, 2 screws, or no screws were inserted 2-mm proud of the articular surface.
      Each specimen was imaged with a conventional fluoroscope and a 3D imaging
      fluoroscope. Overall, 36 image sets were prepared for each modality. These were
      evaluated by 2 fellowship-trained surgeons for intraobserver and interobserver
      reliability as well for the accuracy of detecting prominent implants in the 2
      imaging methods. RESULTS: Overall accuracy for observer A was 89.9% compared with
      100% for C-arm fluoroscopy and 3D imaging fluoroscopy (P < .01) and for observer
      B was 91.1% and 100% (P = .01), respectively. The kappa values were 0.74 with C
      arm fluoroscopy and 1.0 for the 3D imaging fluoroscopy for observer A, and 0.93
      and 1.0, respectively, for observer B. CONCLUSIONS: In a proximal humeral
      fracture model, C-arm fluoroscopy is a highly accurate imaging modality that can
      minimize the incidence of penetrating screws into the joint. Further clinical
      studies are required to establish this modality.

PMID- 24581876
TI  - Prospective, randomized comparative study between single-port laparoscopic
      appendectomy and conventional laparoscopic appendectomy.
AB  - INTRODUCTION: Laparoscopic appendectomy is probably the technique of choice in
      acute appendicitis. Single port laparoscopic surgery (SILS) has been proposed as
      an alternative technique. The objective of this study is to compare the safety
      and efficacy of SILS against conventional laparoscopic appendectomy (LA).
      MATERIAL AND METHODS: From January 2011 to September 2012, 120 patients with
      acute appendicitis were prospectively randomized; 60 for SILS and 60 for LA.
      Patients between 15 to 65 years were selected, with onset of symptoms less than
      48h. We compared BMI, surgery time, start of oral intake, hospital stay,
      postoperative pain, pathology and costs. RESULTS: The median age, BMI, sex and
      time of onset of symptoms to diagnosis were similar. There were no statistically
      significant differences in the operative time, start of oral intake or hospital
      stay. There was a significant difference in postoperative pain being higher in
      SILS (4+/-1.3) than in LA (3.3+/-0.5) with a P=.004. Flemonous appendicitis
      predominated in both groups in a similar percentage. A total of 3 cases with
      intra-abdominal abscess (SILS 2, LA 1) required readmission and resolved
      spontaneously with intravenous antibiotic treatment. One case of SILS required
      assistance by a 5mm trocar in the RLC for drainage placement. The cost was higher
      in SILS due the single port device. CONCLUSION: SILS appendectomy is safe,
      effective and has similar results to LA in selected patients, and although the
      cost is greater, the long term results will determine the future of this
      technique.

PMID- 24581877
TI  - [Severe maintained hypocalcemia after parathyroidectomy for hyperparathyroidism
      in a patient with multiple endocrine neoplasia I and prior bariatric surgery].

PMID- 24581878
TI  - From Miles' procedure to robotic transanal proctectomy.

PMID- 24581879
TI  - Giant presacral myelolipoma.

PMID- 24581880
TI  - Abdominal wall closure after a stomal reversal procedure.
AB  - The closure of a temporary stoma involves 2 different surgical procedures: the
      stoma reversal procedure and the abdominal wall reconstruction of the stoma site.
      The management of the abdominal wall has different areas that should be analyzed
      such us how to avoid surgical site infection (SSI), the technique to be used in
      case of a concomitant hernia at the stoma site or to prevent an incisional hernia
      in the future, how to deal with the incision when the stoma reversal procedure is
      performed by laparoscopy and how to close the skin at the stoma site. The aim of
      this paper is to analyze these aspects in relation to abdominal wall
      reconstruction during a stoma reversal procedure.

PMID- 24581882
TI  - Spur cell anemia in end-stage liver disease: a zebra!

PMID- 24581881
TI  - Escherichia coli isolates from inflammatory bowel diseases patients survive in
      macrophages and activate NLRP3 inflammasome.
AB  - Crohn's disease (CD) is a multifactorial pathology associated with the presence
      of adherent-invasive Escherichia coli (AIEC) and NLRP3 polymorphic variants. The
      presence of intracellular E. coli in other intestinal pathologies (OIP) and the
      role of NLRP3-inflammasome in the immune response activated by these bacteria
      have not been investigated. In this study, we sought to characterize
      intracellular strains isolated from patients with CD, ulcerative colitis (UC) and
      OIP, and analyze NLRP3-inflammasome role in the immune response and bactericidal
      activity induced in macrophages exposed to invasive bacteria. For this,
      intracellular E. coli isolation from ileal biopsies, using gentamicin-protection
      assay, revealed a prevalence and CFU/biopsy of E. coli higher in biopsies from
      CD, UC and OIP patients than in controls. To characterize bacterial isolates,
      pulsed-field gel electrophoresis (PFGE) patterns, virulence genes, serogroup and
      phylogenetic group were analyzed. We found out that bacteria isolated from a
      given patient were closely related and shared virulence factors; however, strains
      from different patients were genetically heterogeneous. AIEC characteristics in
      isolated strains, such as invasive and replicative properties, were assessed in
      epithelial cells and macrophages, respectively. Some strains from CD and UC
      demonstrated AIEC properties, but not strains from OIP. Furthermore, the role of
      NLRP3 in pro-inflammatory cytokines production and bacterial elimination was
      determined in macrophages. E. coli strains induced IL-1beta through NLRP3
      dependent mechanism; however, their elimination by macrophages was independent of
      NLRP3. Invasiveness of intracellular E. coli strains into the intestinal mucosa
      and IL-1beta production may contribute to CD and UC pathogenesis. 

PMID- 24581883
TI  - Subarachnoid hemorrhage and pneumocephalus due to epidural anesthesia.

PMID- 24581884
TI  - It is not a tumor: a rare case of tumefactive multiple sclerosis.

PMID- 24581885
TI  - Adding ivabradine may reduce elevated heart rate in acute patients when beta
      blockers are ineffective.

PMID- 24581886
TI  - Anaphylaxis after intramuscular injection of diclofenac sodium.
AB  - Diclofenac sodium is a 2-arylacetic acid, nonsteroidal anti-inflammatory drug. It
      is widely used in pain management. Side effects such as urticaria, asthmatic
      attack, vasospastic angina, ischemic stroke, and Kounis syndrome may be seen
      after the use of diclofenac sodium. However, anaphylactic shock is rare.
      Anaphylactic shock secondary to injection of diclofenac sodium can be treated
      successfully with intramuscular injection of adrenaline. Because diclofenac
      sodium is commonly used in analgesic treatment in emergency departments, we
      present this case report to emphasize that anaphylactic shock may be seen after
      the use of that drug.

PMID- 24581887
TI  - A novel automatic staffing allocation tool based on workload and cognitive load
      intensity.

PMID- 24581888
TI  - Thoracic spine fracture in the course of severe nocturnal hypoglycemia in young
      patients with type 1 diabetes mellitus--the role of low bone mineral density.
AB  - Thus far, only a few spine fracture cases related to severe nocturnal
      hypoglycemia in type 1 diabetes patients have been reported. Due to the
      relatively young age of these subjects, osteoporosis was not taken into
      consideration and bone mineral density was not assessed. We report three type 1
      diabetes cases in young patients with durations of 2, 4, and 19 years. These
      patients had severe hypoglycemic attacks during night sleep with subsequent
      compression thoracic vertebrae fractures. Laboratory parameters for diabetes
      control, calcium, phosphate metabolism and celiac-specific antibodies were
      assessed. Moreover, kidney, thyroid, and parathyroid gland functions were also
      measured. Bone mineral density was assessed by dual energy x-ray absorptiometry.
      Lumbar spine x-ray absorptiometry revealed very low bone mineral density in all
      three patients. In all subjects, metabolic control was good, no chronic diabetes
      complications were found and other laboratory parameters were within a normal
      range. For the first time, it was demonstrated that low bone mineral density in
      young type 1 diabetes patients may contribute to an increased compression
      fracture risk of the dorsal spine during severe nocturnal hypoglycemia courses.
      The possibility of osteoporosis in young patients with short diabetes durations
      suggests it might be advisable to perform bone mineral density testing during
      diabetes diagnoses. Spinal pain occurrences in young patients after severe
      nocturnal hypoglycemia should be investigated using procedures for the diagnosis
      of vertebral compression fracture, even if there is no evident trauma.

PMID- 24581889
TI  - Validity of the Spanish version of the Emotional Labour Scale.
AB  - In this article we address concerns raised by Brumit and Glenn (2013) regarding
      the validity of the Spanish version of the Emotional Labour Scale (ELS). We
      respond to requests in relation to the translated version of the scale and the
      eigenvalue series. We also give an explanation of the differences in results
      between the original version and the Spanish version of the scale. 

PMID- 24581890
TI  - An information communication technology based approach for the acquisition of
      critical thinking skills.
AB  - BACKGROUND: Both academics and practitioners agree that critical thinking skills
      are necessary to provide safe and comprehensive nursing care. In order to promote
      the development of critical thinking, nurse educators need to keep the
      teaching/learning process captivating and interesting using active learning
      environments. These can be implemented by using modern information and
      communication technologies that are simple, fun, and time and cost effective.
      OBJECTIVES: The goal of our study was to design and test an approach, which
      allows individual and fast acquisition of critical thinking skills with the use
      of information and communication technology. DESIGN: A combination of qualitative
      and quantitative research design was implemented. The study consisted of a quasi
      experiment (phases 1-3): (1) pre-test discussion board, (2) use of e-contents
      based on the presented approach, and (3) post-test discussion board. The
      participants' opinion about the presented approach was identified in phase 4.
      SETTINGS: The study was performed in May 2012 during the course "Ethics and
      Philosophy in Nursing" at the Faculty of Health Sciences, University of
      Primorska, Slovenia. PARTICIPANTS: Forty first-year undergraduate nursing
      students. METHODS: Qualitative analysis of the discussion boards (phases 1, 3)
      and an anonymous survey with open- and closed-ended questions (phase 4). RESULTS:
      Qualitative analysis of the discussion boards showed a significant (p<0.001)
      improvement in the percentage of posts (12.2%) for which the opinions and
      conclusions of the participants were justified with valid arguments. The survey
      results indicated that participants perceived the e-contents based on the
      presented approach as useful, and that they improved their critical thinking
      skills. CONCLUSIONS: Repeated confirmation of the validity of the presented
      approach through methodological triangulation represents a strong indication that
      the presented approach is a valuable tool to develop nursing students' critical
      thinking skills.

PMID- 24581891
TI  - [Hepatic artery aneurysm rupture after lumbar stenosis surgery. Medico-legal
      thinking].
AB  - INTRODUCTION: Distinguishing between therapeutic contingency and surgical
      complication is sometimes not easy, especially when rare events occur. We report
      the case of a patient who presented with an intraperitoneal haemorrhage following
      laminectomy and discuss the implications of surgery in this complication. CASE
      REPORT: A 77-year-old woman, suffering from radiculopathy due to lumbar stenosis
      underwent a laminectomy in the prone position. On admission she presented with
      high blood pressure and obesity as significant comorbidities. A few hours after
      surgery, she collapsed and underwent a thoraco-abdominal CT-scan. The examination
      revealed a ruptured hepatic artery aneurysm. It is the first case published in
      the medical literature after lumbar surgery. The aim of this article was to
      discuss the responsibility of the surgeon and surgery, particularly the surgical
      positioning of the ruptured aneurysm. CONCLUSION: After reviewing the literature
      we did not find any evidence to attribute the rupture of this hepatic artery
      aneurysm to lumbar surgery. This adverse event could be attributed to therapeutic
      contingency. In cases of patient complaint, this situation depends on national
      solidarity.

PMID- 24581892
TI  - Chronic subdural haematoma associated with pre-eclampsia: case report and review
      of the literature.
AB  - Pre-eclampsia complicates approximately 5-8% of all pregnancies and may have
      adverse long-term effects on both mother and child. Chronic atraumatic subdural
      haematoma as a complication of severe pre-eclampsia, in the absence of clotting
      factor abnormalities, is a very rare condition. We present the case of a 30-year
      old Moroccan woman who had a pregnancy 10 years previously, with an uneventful
      delivery. She presented with pre-eclampsia complicating a 29-week-old pregnancy.
      A few days preceding maternity unit admission the patient complained of headaches
      and malaise. Her blood pressure at admission was 150/120mmHg and subsequently was
      treated with doses of methyldopa and magnesium sulphate. Her condition worsened
      with a loss of consciousness 24 hours later and was transferred to the
      neurosurgical unit. A brain computerized tomography (CT) scan revealed a left
      sided subdural haematoma and the patient underwent surgery, with a good
      postoperative outcome. This article highlights the occurrence of neurological
      complications due to pre-eclampsia/eclampsia that require particular
      neurosurgical attention, its treatment and prognosis. We also review the
      literature regarding this pathology.

PMID- 24581893
TI  - [Effect of drug interaction between clopidogrel and omeprazole in hospital
      readmision of patients by a recurrent acute coronary syndrome: a case-control
      study].
AB  - OBJECTIVE: To evaluate the effect of drug interaction between omeprazol and
      clopidogrel in hospital readmission of patients with acute coronary syndrome
      (ACS). DESIGN: Case-control study. LOCATION: University Clinic LeonXIII,
      Medellin, Colombia. PARTICIPANTS: We selected from a prevalent population,
      between 2009-2010, use of clopidogrel patients on an outpatient basis (less than
      one year and more than 30days), and hospital stay for ACS or the presence of a
      previous ACS. MAIN MEASURES: A case-patient was defined as one who had a
      recurrence of ACS and a patient-control is defined as one that no recurrence of
      ACS. Both groups used ambulatory prior clopidogrel due to ACS. As defined risk
      factor the joint use of omeprazole and clopidogrel outpatients. RESULTS: During
      the study, 1680patients clopidogrel formulated. This group identified 50cases
      readmitted with ACS and 76controls. No statistically significant association was
      found between use of clopidogrel-omeprazole and increased risk of hospital
      readmission for ACS (OR: 1.05; 95%CI: 0.516-2.152; P=.8851). CONCLUSIONS: In this
      small group of patients with previous SCA, the simultaneous use of clopidogrel
      with omeprazole does not increase the risk of a readmission by recurrence of this
      type of coronary event.

PMID- 24581895
TI  - Load sharing and ligament strains in balanced, overstuffed and understuffed UKA.
      A validated finite element analysis.
AB  - The aim of this study was to quantify the effects of understuffing and
      overstuffing UKA on bone stresses, load distribution and ligament strains. For
      that purpose, a numerical knee model of a cadaveric knee was developed and was
      validated against experimental measurements on that same knee. Good agreement was
      found among the numerical and experimental results. This study showed that, even
      if a medial UKA is well-aligned with normal soft tissue tension and with correct
      thickness of the tibia component, it induces a stiffness modification in the
      joint that alters the load distribution between the medial and lateral
      compartments, the bone stress and the ligament strain potentially leading to an
      osteoarthritic progression. 

PMID- 24581894
TI  - [Impact of a psychosocial intervention in caregiver burden of children with
      cerebral palsy].
AB  - OBJECTIVE: To demonstrate that problem-solving therapy is effective in reducing
      the burden on caregivers of children with cerebral palsy. DESIGN: Randomized
      clinical trial. LOCATION: Check primary care within a private nonprofit
      association. PARTICIPANTS: 140caregivers divided into control group (CG) and
      experimental group (EG). INTERVENTIONS: We performed in both groups a
      psychosocial intervention with a frequency of one session per week for three
      weeks to complete 120minutes. In the EG performed a shortened form of problem
      solving therapy with a focus on caregiver burden and the CG performed an
      educational intervention focusing on respiratory diseases. MAIN MEASURES: The
      response variable corresponds to the score obtained by Zarit questionnaire. The
      independent variable accounted for psychosocial intervention. RESULTS: In the EG
      according to Zarit questionnaire score was obtained by averaging 45.0 points pre
      intervention against 45.3 points in the CP after intervention Zarit was obtained
      by averaging 29.8 points in the EG and 44.3 points in the CG (P<.0001). The
      catalog groups according to their score Zarit in charge: none, mild, moderate and
      severe impact differences were found in the different intervention categories
      (Wilcoxon test Z=6.281, P<.00001). CONCLUSIONS: Problem solving therapy is
      effective in reducing the burden on caregivers of children with cerebral palsy.

PMID- 24581896
TI  - Anterior distal femoral osteotomy for removal of long femoral stems in revision
      knee arthroplasty.
AB  - Osteotomies of the proximal femur and proximal tibia in revision arthroplasty are
      well described while guidelines for distal femoral osteotomy are limited. Femoral
      stems are used with increasing frequency for fixation of revision components in
      knee arthroplasty and their removal is technically challenging particularly in
      the setting of infection. We describe a technique of anterior distal femoral
      osteotomy for revision knee arthroplasty to assist with removal of well-fixed
      long stemmed cemented or porous femoral components, as well as debridement of
      infection while preserving bone stock and soft tissue attachments. 

PMID- 24581897
TI  - Modern retrograde intramedullary nails versus periarticular locked plates for
      supracondylar femur fractures after total knee arthroplasty.
AB  - This study purpose is to analyze outcomes of modern intramedullary (IM) nails
      with a locked distal screw versus periarticular locking plates for peri
      prosthetic supracondylar femur fractures in TKA. Ninety-five consecutive
      fractures in 91 patients were retrospectively reviewed. Fixation included 29
      knees with a retrograde IM nail and 66 periarticular locked plates. Six patients
      died and 4 were lost to follow-up. There were 2 (9%) nonunions in the IM nail
      group and 12 non-unions/delayed-unions (19%) in the locked plate group (P =
      0.34). A mean of 5.0 distal screws was used in locked plates versus 3.8 distal
      screws in the IM nails (P < 0.001). Despite a greater quantity of screws in the
      distal fragment, the failure rate of locked plating was twice that of IM nail
      fixation.

PMID- 24581898
TI  - A reliable, valid and responsive questionnaire to score the impact of knee
      complaints on work following total knee arthroplasty: the WORQ.
AB  - The Work, Osteoarthritis or joint-Replacement Questionnaire (WORQ) was developed
      to assess physical difficulty experienced in work before or following total knee
      arthroplasty (TKA). Thirteen questions were designed. The WORQ was tested for
      internal consistency by factor analysis, internal reliability (Crohnbach's
      alpha), and construct validity. A test-retest reproducibility was performed for
      analyzing standard error of measurement (SEM agreement), reliability (ICC) and
      smallest detectable change (SDC) in individuals and groups. Lastly responsiveness
      (standardized response means [SRM]), floor and ceiling effects and
      interpretability (minimal important change [MIC]) were analyzed. It is shown that
      the WORQ is a reliable, valid and responsive questionnaire that can be used to
      evaluate the impact of knee complaints following TKA on patients' ability to
      work. 

PMID- 24581899
TI  - Postoperative falls after total knee arthroplasty in patients with a femoral
      nerve catheter: can we reduce the incidence?
AB  - A femoral nerve catheter (FNC) is often used to minimize pain following total
      knee arthroplasty (TKA), but complications including inpatient falls, may
      increase as a result, despite fall prevention protocols. We evaluated the rate of
      falls in 707 primary TKAs performed with an FNC at a major academic center from
      May 2009 to September 2012. Despite a formalized fall prevention protocol, we
      found 19 falls (2.7%). Three patients required further operative intervention. At
      a rate of 2.7%, postoperative fall is one of the most common complications of TKA
      at our institution. While pain control may be good with the use of FNCs following
      primary TKA, improvements in fall prevention strategies or the use of alternative
      postoperative pain control modalities may need to be considered. 

PMID- 24581900
TI  - Transfer of patient care during two-stage exchange for periprosthetic joint
      infection leads to inferior outcomes.
AB  - The two-stage exchange algorithm is the gold standard for managing chronic
      periprosthetic joint infection (PJI); this study evaluated the impact of having
      the stages performed at different institutions. Patients with a chronically
      infected total joint arthroplasty (hip or knee) with initial resection at an
      outside hospital and subsequent care at our institution (transferred group) were
      identified then matched with a similar cohort that received both stages at our
      institution (continuous group). Eighteen patients (transferred group) were
      compared to 36 matched controls. There were significantly lower rates of
      successful reimplantation and retention, longer duration of treatment and more
      procedures in the transferred group compared to the continuous group. Patients
      transferred during their care for chronic PJI underwent more surgeries, longer
      treatment times, and less favorable outcomes. 

PMID- 24581901
TI  - Systematic search and review procedures: results of the International
      Collaboration on Mild Traumatic Brain Injury Prognosis.
AB  - OBJECTIVES: To update the last best-evidence synthesis conducted by the World
      Health Organization Collaborating Centre for Neurotrauma, Prevention, Management
      and Rehabilitation in 2002; and to describe the course, identify prognostic
      factors, determine long-term sequelae, identify effects of interventions for mild
      traumatic brain injury (MTBI), identify knowledge gaps in the literature, and
      make recommendations for future research. DATA SOURCES: MEDLINE, Embase,
      PsycINFO, Cumulative Index to Nursing and Allied Health, and SPORTDiscus were
      searched between 2001 and 2012. Inclusion criteria included published peer
      reviewed articles in English and 5 other languages. References were also
      identified from relevant reviews and meta-analyses and the bibliographies of
      eligible articles. STUDY SELECTION: Controlled trials and cohort and case-control
      studies were selected according to predefined inclusion/exclusion criteria.
      Studies had to have at least 30 MTBI cases and assess outcomes relevant to
      prognosis after MTBI. DATA EXTRACTION: Eligible studies were critically appraised
      using modified Scottish Intercollegiate Guidelines Network (SIGN) criteria. Two
      reviewers independently reviewed each study and extracted data from accepted
      articles (ie, with a low risk of bias) into evidence tables. DATA SYNTHESIS: The
      evidence was synthesized qualitatively according to modified SIGN criteria and
      prioritized according to design as exploratory or confirmatory. The evidence was
      organized into separate articles according to population (eg, adults, children,
      and athletes) and outcomes (eg, risk of dementia after MTBI). CONCLUSIONS: After
      77,914 records were screened, 299 articles were eligible and reviewed. Of these,
      101 (34%) were accepted as scientifically admissible and form the basis of our
      findings, which are organized into 10 articles in this supplement. These reviews
      present the best available evidence on MTBI prognosis, but more research is
      needed.

PMID- 24581902
TI  - Systematic review of self-reported prognosis in adults after mild traumatic brain
      injury: results of the International Collaboration on Mild Traumatic Brain Injury
      Prognosis.
AB  - OBJECTIVE: To update the mild traumatic brain injury (MTBI) prognosis review
      published by the World Health Organization Task Force in 2004. DATA SOURCES:
      MEDLINE, PsycINFO, Embase, CINAHL, and SPORTDiscus were searched from 2001 to
      2012. We included published, peer-reviewed studies with more than 30 adult cases.
      STUDY SELECTION: Controlled trials and cohort and case-control studies were
      selected according to predefined criteria. Studies had to assess subjective, self
      reported outcomes. After 77,914 titles and abstracts were screened, 299 articles
      were eligible and reviewed for scientific quality. This includes 3 original
      International Collaboration on MTBI Prognosis (ICoMP) research studies. DATA
      EXTRACTION: Eligible studies were critically appraised using the Scottish
      Intercollegiate Guidelines Network criteria. Two reviewers independently reviewed
      each study and tabled data from accepted articles. A third reviewer was consulted
      for disagreements. DATA SYNTHESIS: Evidence from accepted studies was synthesized
      qualitatively into key findings, and prognostic information was prioritized
      according to design as exploratory or confirmatory. Of 299 reviewed studies, 101
      (34%) were accepted and form our evidence base of prognostic studies. Of these,
      23 addressed self-reported outcomes in adults, including 2 of the 3 original
      ICoMP research studies. These studies show that common postconcussion symptoms
      are not specific to MTBI/concussion and occur after other injuries as well. Poor
      recovery after MTBI is associated with poorer premorbid mental and physical
      health status and with more injury-related stress. Most recover over 1 year, but
      persistent symptoms are more likely in those with more acute symptoms and more
      emotional stress. CONCLUSIONS: Common subjective symptoms after MTBI are not
      necessarily caused by brain injury per se, but they can be persistent in some
      patients. Those with more initial complaints and psychological distress recover
      slower. We need more high-quality research on these issues.

PMID- 24581903
TI  - Systematic review of the prognosis after mild traumatic brain injury in adults:
      cognitive, psychiatric, and mortality outcomes: results of the International
      Collaboration on Mild Traumatic Brain Injury Prognosis.
AB  - OBJECTIVE: To synthesize the best available evidence on objective outcomes after
      adult mild traumatic brain injury (MTBI). DATA SOURCES: MEDLINE and other
      databases were searched (2001-2012) for studies related to MTBI. Inclusion
      criteria included published, peer-reviewed articles in English and other
      languages. References were also identified from the bibliographies of eligible
      articles. STUDY SELECTION: Randomized controlled trials and cohort and case
      control studies were selected according to predefined criteria. Studies had to
      have a minimum of 30 MTBI cases and assess objective outcomes in adults. DATA
      EXTRACTION: Eligible studies were critically appraised using a modification of
      the Scottish Intercollegiate Guidelines Network (SIGN) criteria. Two reviewers
      independently reviewed each study and extracted data from accepted articles into
      evidence tables. DATA SYNTHESIS: Evidence was synthesized qualitatively according
      to modified SIGN criteria, and studies were categorized as exploratory or
      confirmatory based on the strength of their design and evidence. After 77,914
      records were screened, 299 were found to be relevant and critically reviewed, and
      101 were deemed scientifically admissible. Of these, 21 studies that were related
      to the objective outcomes form the basis of this review. Most evidence indicates
      the presence of cognitive deficits in the first 2 weeks post-MTBI, and some
      evidence suggests that complete recovery may take 6 months or a year. A small
      number of studies indicate that MTBI increases the risk of psychiatric illnesses
      and suicide. CONCLUSIONS: Early cognitive deficits are common, and complete
      recovery may be prolonged. Conclusions about mortality post-MTBI are limited.
      This review has implications for expected recovery after MTBI and MTBI-related
      health sequelae. Well-designed confirmatory studies are needed to understand the
      medium- to long-term consequences of MTBI and to further evaluate the effect of
      prior MTBI and injury severity on recovery.

PMID- 24581904
TI  - Systematic review of the clinical course, natural history, and prognosis for
      pediatric mild traumatic brain injury: results of the International Collaboration
      on Mild Traumatic Brain Injury Prognosis.
AB  - OBJECTIVE: To synthesize the best available evidence on prognosis after pediatric
      mild traumatic brain injury (MTBI). DATA SOURCES: We searched MEDLINE, Embase,
      PsycINFO, CINAHL, and SPORTDiscus (2001-2012), as well as reference lists of
      eligible articles, and relevant systematic reviews and meta-analyses. STUDY
      SELECTION: Controlled trials and cohort and case-control studies were selected
      according to predefined criteria. Studies had to have a minimum of 30 MTBI
      pediatric cases. After 77,914 records were screened for the entire review, 299
      studies were eligible and assessed for scientific rigor. DATA EXTRACTION:
      Eligible studies were critically appraised using the Scottish Intercollegiate
      Guidelines Network (SIGN) criteria. Two reviewers independently reviewed each
      study and extracted data from accepted articles into evidence tables. DATA
      SYNTHESIS: Evidence from 25 accepted articles was synthesized qualitatively
      according to SIGN criteria, and prognostic information was prioritized according
      to design as exploratory or confirmatory. Most studies show that postconcussion
      symptoms and cognitive deficits resolve over time. Limited evidence suggests that
      postconcussion symptoms may persist in those with lower cognitive ability and
      intracranial pathology on neuroimaging. Preliminary evidence suggests that the
      risk of epilepsy is increased for up to 10 years after MTBI; however, there is
      insufficient high-quality evidence at this time to support this link.
      CONCLUSIONS: Common post-MTBI symptoms and deficits in children are not specific
      to MTBI and appear to resolve with time; however, limited evidence suggests that
      children with intracranial pathology on imaging may experience persisting
      symptoms or deficits. Well-designed, long-term studies are needed to confirm
      these findings.

PMID- 24581905
TI  - Psychosocial consequences of mild traumatic brain injury in children: results of
      a systematic review by the International Collaboration on Mild Traumatic Brain
      Injury Prognosis.
AB  - OBJECTIVE: To synthesize the best available evidence regarding psychosocial
      consequences of mild traumatic brain injury (MTBI) in children. DATA SOURCES:
      MEDLINE, Embase, CINAHL, PsycINFO, and SPORTDiscus were searched (2001-2012).
      Inclusion criteria included published peer-reviewed reports in English, French,
      Norwegian, Spanish, Swedish, and Danish. References were also identified from
      relevant reviews and meta-analyses, and the bibliographies of eligible articles.
      STUDY SELECTION: This article presents an update of a previous review with a much
      larger scope, of which this topic is a small subset of the questions addressed by
      that review. Controlled trials and cohort and case-control studies were selected
      according to predefined criteria. Two independent reviewers used modified
      Scottish Intercollegiate Guidelines Network criteria to critically appraise
      eligible studies. A total of 77,914 records were screened; 101 of these articles
      were deemed scientifically admissible, of which 6 investigated the psychosocial
      consequences of MTBI in children. DATA EXTRACTION: Two reviewers independently
      extracted data from accepted studies into evidence tables. DATA SYNTHESIS: We
      conducted a best-evidence synthesis by linking our conclusions to the evidence
      tables. Most accepted studies were exploratory rather than confirmatory.
      Preliminary evidence suggests that most children recover within 3 months post
      MTBI. After 1 year, the prevalence of postconcussion symptoms and syndrome is
      similar between children with MTBI and children with orthopedic injuries. The
      functional status of children with MTBI improves over a 30-month follow-up
      period, but further research is needed to investigate the possibility that
      children with MTBI experience greater rates of psychiatric illness during the 3
      years after their injury. CONCLUSIONS: The prognosis of MTBI is favorable in
      children. Most appear to recover functionally from a physical and psychological
      perspective. However, future research should investigate the risk for psychiatric
      illness.

PMID- 24581906
TI  - Systematic review of return to work after mild traumatic brain injury: results of
      the International Collaboration on Mild Traumatic Brain Injury Prognosis.
AB  - OBJECTIVE: To synthesize the best available evidence on return to work (RTW)
      after mild traumatic brain injury (MTBI). DATA SOURCES: MEDLINE and other
      databases were searched (2001-2012) with terms including "craniocerebral trauma"
      and "employment." Reference lists of eligible articles were also searched. STUDY
      SELECTION: Controlled trials and cohort and case-control studies were selected
      according to predefined criteria. Studies had to assess RTW or employment
      outcomes in at least 30 MTBI cases. DATA EXTRACTION: Eligible studies were
      critically appraised using a modification of the Scottish Intercollegiate
      Guidelines Network criteria. Two reviewers independently reviewed and extracted
      data from accepted studies into evidence tables. DATA SYNTHESIS: Evidence was
      synthesized qualitatively according to modified Scottish Intercollegiate
      Guidelines Network criteria and prioritized according to design as exploratory or
      confirmatory. After 77,914 records were screened, 299 articles were found
      eligible and reviewed; 101 (34%) of these with a low risk of bias were accepted
      as scientifically admissible, and 4 of these had RTW or employment outcomes. This
      evidence is preliminary and suggests that most workers RTW within 3 to 6 months
      after MTBI; MTBI is not a significant risk factor for long-term work disability;
      and predictors of delayed RTW include a lower level of education (<11y of formal
      education), nausea or vomiting on hospital admission, extracranial injuries,
      severe head/bodily pain early after injury, and limited job independence and
      decision-making latitude. CONCLUSIONS: Our findings are based on preliminary
      evidence with varied patient characteristics and MTBI definitions, thus limiting
      firm conclusions. More well-designed studies are required to understand RTW and
      sustained employment after MTBI in the longer term (>=2y post-MTBI).

PMID- 24581907
TI  - Systematic review of prognosis and return to play after sport concussion: results
      of the International Collaboration on Mild Traumatic Brain Injury Prognosis.
AB  - OBJECTIVE: To synthesize the best available evidence on prognosis after sport
      concussion. DATA SOURCES: MEDLINE and other databases were searched (2001-2012)
      with terms including "craniocerebral trauma" and "sports." Reference lists of
      eligible articles were also searched. STUDY SELECTION: Randomized controlled
      trials and cohort and case-control studies were selected according to predefined
      criteria. Studies had to have a minimum of 30 concussion cases. DATA EXTRACTION:
      Eligible studies were critically appraised using a modification of the Scottish
      Intercollegiate Guidelines Network (SIGN) criteria. Two reviewers independently
      reviewed and extracted data from accepted studies into evidence tables. DATA
      SYNTHESIS: Evidence was synthesized qualitatively according to modified SIGN
      criteria, and studies were categorized as exploratory or confirmatory based on
      the strength of their design and evidence. After 77,914 records were screened, 52
      articles were eligible for this review, and 24 articles (representing 19 studies)
      with a low risk of bias were accepted. Our findings are based on exploratory
      studies of predominantly male football players at the high school, collegiate,
      and professional levels. Most athletes recover within days to a few weeks, and
      American and Australian professional football players return to play quickly
      after mild traumatic brain injury. Delayed recovery appears more likely in high
      school athletes, in those with a history of previous concussion, and in those
      with a higher number and duration of postconcussion symptoms. CONCLUSIONS: The
      evidence concerning sports concussion course and prognosis is very preliminary,
      and there is no evidence on the effect of return-to-play guidelines on prognosis.
      Our findings have implications for further research. Well-designed, confirmatory
      studies are urgently needed to understand the consequences of sport concussion,
      including recurrent concussion, across different athletic populations and sports.

PMID- 24581908
TI  - Systematic review of prognosis after mild traumatic brain injury in the military:
      results of the International Collaboration on Mild Traumatic Brain Injury
      Prognosis.
AB  - OBJECTIVE: The World Health Organization Collaborating Centre Task Force on Mild
      Traumatic Brain Injury (MTBI) published its findings on the prognosis of MTBI in
      2004. This is an update of that review with a focus on deployed military
      personnel. DATA SOURCES: Relevant literature published between January 2001 and
      February 2012 listed in MEDLINE and 4 other databases. STUDY SELECTION:
      Controlled trials and cohort and case-control studies were selected according to
      predefined criteria. After 77,914 titles and abstracts were screened, 13 articles
      were rated eligible for this review and 3 (23%) with a low risk of bias were
      accepted. Two independent reviewers critically appraised eligible studies using a
      modification of the Scottish Intercollegiate Guidelines Network criteria. DATA
      EXTRACTION: The reviewers independently extracted data from eligible studies and
      produced evidence tables. DATA SYNTHESIS: The evidence was synthesized
      qualitatively and presented in evidence tables. Our findings are based on 3
      studies of U.S. military personnel who were deployed in Iraq or Afghanistan. We
      found that military personnel with MTBI report posttraumatic stress disorder and
      postconcussive symptoms. In addition, reporting of postconcussive symptoms
      differed on the basis of levels of combat stress the individuals experienced. The
      evidence suggests a slight decline in neurocognitive function after MTBI, but
      this decline was in the normal range of brain functioning. CONCLUSIONS: We found
      limited evidence that combat stress, posttraumatic stress disorder, and
      postconcussive symptoms affect recovery and prognosis of MTBI in military
      personnel. Additional high-quality research is needed to fully assess the
      prognosis of MTBI in military personnel.

PMID- 24581909
TI  - Systematic review of the risk of Parkinson's disease after mild traumatic brain
      injury: results of the International Collaboration on Mild Traumatic Brain Injury
      Prognosis.
AB  - OBJECTIVE: To synthesize the best available evidence on the risk of Parkinson's
      disease (PD) after mild traumatic brain injury (MTBI). DATA SOURCES: MEDLINE and
      other databases were searched (1990-2012) with terms including "craniocerebral
      trauma" and "parkinsonian disorders." Reference lists of eligible articles and
      relevant systematic reviews and meta-analyses were also searched. STUDY
      SELECTION: Controlled clinical trials, cohort studies, and case-control studies
      were selected according to predefined criteria. Studies had to have a minimum of
      30 concussion cases. DATA EXTRACTION: Eligible studies were critically appraised
      using a modification of the Scottish Intercollegiate Guidelines Network criteria.
      Two reviewers independently reviewed and extracted data from accepted studies
      into evidence tables. DATA SYNTHESIS: Evidence was synthesized qualitatively
      according to modified Scottish Intercollegiate Guidelines Network criteria. Sixty
      five studies were eligible and reviewed, and 5 of these with a low risk of bias
      were accepted as scientifically admissible and form the basis of our findings.
      Among these admissible studies, the definitions of MTBI were highly
      heterogeneous. One study found a significant positive association between MTBI
      and PD (odds ratio, 1.5; 95% confidence interval, 1.4-1.7). The estimated odds
      ratio decreased with increasing latency between MTBI and PD diagnosis, which
      suggests reverse causality. The other 4 studies did not find a significant
      association. CONCLUSIONS: The best available evidence argues against an important
      causal association between MTBI and PD. There are few high-quality studies on
      this topic. Prospective studies of long duration would address the limitations of
      recall of head injury and the possibility of reverse causation.

PMID- 24581910
TI  - Systematic review of the risk of dementia and chronic cognitive impairment after
      mild traumatic brain injury: results of the International Collaboration on Mild
      Traumatic Brain Injury Prognosis.
AB  - OBJECTIVE: To synthesize the best available evidence regarding the risk of
      dementia and chronic cognitive impairment (CCI) after mild traumatic brain injury
      (MTBI). DATA SOURCES: MEDLINE and other databases were searched (2001-2012) using
      a previously published search strategy and predefined criteria. Peer-reviewed
      reports in 6 languages were considered. STUDY SELECTION: Systematic reviews, meta
      analyses, randomized controlled trials, cohort studies, and case-control studies,
      with a minimum of 30 MTBI cases in subjects of any age, assessing the risk of
      dementia or CCI after MTBI were selected. DATA EXTRACTION: Eligible studies were
      critically appraised using a modification of the Scottish Intercollegiate
      Guidelines Network criteria. Two reviewers independently reviewed each study and
      extracted data from accepted articles (ie, with a low risk of bias) into evidence
      tables. DATA SYNTHESIS: Evidence from accepted studies was synthesized
      qualitatively according to modified Scottish Intercollegiate Guidelines Network
      criteria, and prognostic information was prioritized as exploratory or
      confirmatory according to design. Of 77,914 records screened, 299 articles were
      eligible and reviewed. Methodological quality was acceptable for 101 (34%)
      articles, of which 1 article considered dementia and 7 articles considered CCI.
      The study examining the risk of dementia after MTBI did not find an association.
      One randomized controlled trial found that being informed about possible
      cognitive dysfunction after MTBI was associated with worse cognitive performance
      on standard tests. Children with MTBI and intracranial pathology ("complicated"
      MTBI) performed worse than did children without intracranial pathology. Children
      showed higher rates of cognitive symptoms a year after MTBI than did a control
      group. CONCLUSIONS: There is a lack of evidence of an increased risk of dementia
      after MTBI. In children, objective evidence of CCI exists only for complicated
      MTBI. More definitive studies are needed to inform clinical decisions, assessment
      of prognosis, and public health policy.

PMID- 24581911
TI  - Nonsurgical interventions after mild traumatic brain injury: a systematic review.
      Results of the International Collaboration on Mild Traumatic Brain Injury
      Prognosis.
AB  - OBJECTIVE: To synthesize the best available evidence regarding the impact of
      nonsurgical interventions on persistent symptoms after mild traumatic brain
      injury (MTBI). DATA SOURCES: MEDLINE and other databases were searched (2001
      2012) with terms including "rehabilitation." Inclusion criteria were original,
      peer-reviewed research published in English and other languages. References were
      also identified from the bibliographies of eligible articles. STUDY SELECTION:
      Controlled trials and cohort and case-control studies were selected according to
      predefined criteria. Studies had to have a minimum of 30 MTBI cases and assess
      nonsurgical interventions using clinically relevant outcomes such as self-rated
      recovery. DATA EXTRACTION: Eligible studies were critically appraised using a
      modification of the Scottish Intercollegiate Guidelines Network (SIGN) criteria.
      Two reviewers independently reviewed each study and extracted data from the
      admissible studies into evidence tables. DATA SYNTHESIS: The evidence was
      synthesized qualitatively according to the modified SIGN criteria.
      Recommendations were linked to the evidence tables using a best-evidence
      synthesis. After 77,914 records were screened, only 2 of 7 studies related to
      nonsurgical interventions were found to have a low risk of bias. One studied the
      effect of a scheduled telephone intervention offering counseling and education on
      outcome and found a significantly better outcome for symptoms (6.6 difference in
      adjusted mean symptom score; 95% confidence interval, 1.2-12.0), but no
      difference in general health outcome at 6 months after MTBI. The other was a
      randomized controlled trial of the effectiveness of 6 days of bed rest on
      posttraumatic complaints 6 months postinjury, compared with no bed rest, and
      found no effect. CONCLUSIONS: Some evidence suggests that early, reassuring
      educational information is beneficial after MTBI. Well-designed intervention
      studies are required to develop effective treatments and improve outcomes for
      adults and children at risk for persistent symptoms after MTBI.

PMID- 24581912
TI  - Methodological issues and research recommendations for prognosis after mild
      traumatic brain injury: results of the International Collaboration on Mild
      Traumatic Brain Injury Prognosis.
AB  - The International Collaboration on Mild Traumatic Brain Injury (MTBI) Prognosis
      performed a comprehensive search and critical review of the literature from 2001
      to 2012 to update the 2002 best-evidence synthesis conducted by the World Health
      Organization Collaborating Centre for Neurotrauma, Prevention, Management and
      Rehabilitation Task Force on the prognosis of MTBI. Of 299 relevant studies, 101
      were accepted as scientifically admissible. The methodological quality of the
      research literature on MTBI prognosis has not improved since the 2002 Task Force
      report. There are still many methodological concerns and knowledge gaps in the
      literature. Here we report and make recommendations on how to avoid
      methodological flaws found in prognostic studies of MTBI. Additionally, we
      discuss issues of MTBI definition and identify topic areas in need of further
      research to advance the understanding of prognosis after MTBI. Priority research
      areas include but are not limited to the use of confirmatory designs, studies of
      measurement validity, focus on the elderly, attention to litigation/compensation
      issues, the development of validated clinical prediction rules, the use of MTBI
      populations other than hospital admissions, continued research on the effects of
      repeated concussions, longer follow-up times with more measurement periods in
      longitudinal studies, an assessment of the differences between adults and
      children, and an account for reverse causality and differential recall bias. Well
      conducted studies in these areas will aid our understanding of MTBI prognosis and
      assist clinicians in educating and treating their patients with MTBI. 

PMID- 24581914
TI  - Mild traumatic brain injury after motor vehicle collisions: what are the symptoms
      and who treats them? A population-based 1-year inception cohort study.
AB  - OBJECTIVE: To describe the 1-year course of symptoms following mild traumatic
      brain injury (MTBI) sustained in a motor vehicle collision as well as patterns of
      care-seeking. DESIGN: One-year follow-up of a population-based inception cohort.
      SETTING: The province of Saskatchewan, Canada, with a population of about
      1,000,000 inhabitants. PARTICIPANTS: Persons (N=1716) sustaining an MTBI during a
      car collision between November 1997 and December 1999. INTERVENTIONS: Not
      applicable. MAIN OUTCOME MEASURES: We report the prevalence of sleep
      disturbances, tiredness, dizziness, forgetfulness, vision problems, hearing
      problems, headache, neck pain, mid back pain, and low back pain at 6 weeks and 3,
      6, 9, and 12 months postcollision. At the same time points, we report self
      reported care-seeking from registered health care professionals. RESULTS: A total
      of 1716 adults suffered MTBI after a motor vehicle collision over the 2-year
      inception period. Six weeks after the collision, 75% reported having more than 3
      symptoms and 30% had clinically significant pain in more than 3 body sites. Over
      time, the prevalence of symptoms and pain decreased but they were still common
      after 1 year. Almost all participants sought care for their symptoms at all time
      points, most commonly from a physician. Care-seeking from physiotherapists,
      chiropractors, and massage therapists was also very common, and most participants
      sought care from 2 or 3 providers at all follow-up points. CONCLUSIONS: Up to 1
      year after sustaining an MTBI during a motor vehicle collision, multiple symptoms
      and pain in several anatomical sites are common. Care-seeking from multiple
      providers continues throughout the first year postinjury.

PMID- 24581913
TI  - Population-based, inception cohort study of the incidence, course, and prognosis
      of mild traumatic brain injury after motor vehicle collisions.
AB  - OBJECTIVE: To determine the incidence, course, and prognosis of adult mild
      traumatic brain injury (MTBI) caused by motor vehicle collisions. DESIGN:
      Prospective, population-based, inception cohort study. SETTING: The province of
      Saskatchewan, Canada, with a population of about 1,000,000 inhabitants.
      PARTICIPANTS: All adults (N=1716) incurring an MTBI in a motor vehicle collision
      between November 1997 and December 1999 in Saskatchewan. INTERVENTIONS: Not
      applicable. MAIN OUTCOME MEASURES: Age- and sex-stratified incidence rates, time
      to self-reported recovery, and prognostic factors over a 1-year follow-up.
      RESULTS: Of 7170 adults injured in a motor vehicle collision over the 2-year
      inception period, 1716 (24%) met our cohort definition of MTBI. There were more
      women affected (53%), and MTBI was most common in the 18- to 23-year-old group.
      Most were not hospitalized (73%), but 28% reported loss of consciousness and 23%
      reported posttraumatic amnesia. The annual incidence of MTBI per 100,000 adults
      was 106.1 (95% confidence interval [CI], 98.9-113.6) in the first year and 118.3
      (95% CI, 110.8-126.3) in the second year of the study. The 1-year follow-up rate
      was 84%. The median time to recovery was 100 days (95% CI, 97-103), and about 23%
      reported not having recovered by 1 year. Factors associated with delayed recovery
      included being older than 50 years, having less than a high school education,
      having poor expectations for recovery, having depressive symptoms, having arm
      numbness, having hearing problems, having headaches, having low back pain, and
      having thoracic back pain. Loss of consciousness and posttraumatic amnesia were
      not associated with recovery. CONCLUSIONS: MTBI affects almost a quarter of
      persons reporting an injury after a traffic collision. The median time to
      recovery is 100 days, but 23% have still not recovered by 1 year. A mix of
      biopsychosocial factors is associated with recovery, including a strong effect of
      poor expectations for recovery.

PMID- 24581915
TI  - Health care utilization of workers' compensation claimants associated with mild
      traumatic brain injury: a historical population-based cohort study of workers
      injured in 1997-1998.
AB  - OBJECTIVE: To compare the health care use of workers with an injury before and
      after making a workers' compensation claim for mild traumatic brain injury
      (MTBI). DESIGN: Cohort study of workers with an MTBI who received workers'
      compensation benefits. SETTING: Workers' compensation system in Ontario, Canada.
      PARTICIPANTS: Workers (N=728) who made an incident claim involving MTBI to the
      Ontario Workplace Safety and Insurance Board between 1997 and 1998. We linked
      workers' compensation and Ontario Health Insurance Plan files and collected all
      health care services accrued during the year before and 2 years after the claim
      was initiated. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: We report
      our results as a 7-day simple moving average of health care services per 1000
      claimants per day. We stratified our analysis by age, sex, the preclaim level of
      health care utilization, diagnostic category, and health care specialty. RESULTS:
      Over the 2 years, 728 claims related to MTBI were filed by workers with an
      injury. The majority of the claims (65.8%) were filed by men, and 28.3% were
      filed by those aged between 25 and 34 years. The cumulative rate of health care
      utilization was stable (mean=67.6 visits/1000 claimants per day; 95% confidence
      interval [CI], 65.0-70.2) throughout the year before claim initiation. Health
      care utilization peaked during the first 4 weeks following the initiation of the
      claim (mean=274.3 visits/1000 claimants per day; 95% CI, 172.2-376.4) and
      remained on average 182% higher than that at baseline throughout the 5th to 12th
      week postclaim. Two years after the initiation of the claim, utilization remained
      9.5% higher than the preclaim level. The increase was more pronounced (125%
      higher) for workers with less than the median preclaim utilization level.
      CONCLUSIONS: Making a workers' compensation claim involving MTBI is associated
      with a long-term increase in health care use.

PMID- 24581916
TI  - Introduction to the findings of the International Collaboration on Mild Traumatic
      Brain Injury Prognosis: what is a prognostic study?
AB  - Prognostic studies of mild traumatic brain injury (MTBI) can serve many purposes.
      First, they are used to describe paths and outcomes of patients with MTBI.
      Second, they provide information on which characteristics are associated with the
      occurrence of outcomes. Third, they provide insight into the causation of poor or
      favorable course of the disease. Finally, they can assess how differences in the
      probability of outcomes can help predict the course of patients. In this article,
      we summarize methodologic principles used by the International Collaboration on
      MTBI Prognosis to appraise the prognostic literature. Differentiating prognostic
      factors (causally linked with outcome), prognostic markers (associated but not
      causally), and predictors is important to guide interventions, public health
      policy, and research. Ideally, prognostic studies need a clear statement of the
      type of question (hypothesis-generating descriptive, exploration of possible
      prognostic variables, confirmatory modeling of prognosis); a cohort study design
      with standardized follow-up of a representative population of patients with MTBI;
      a standardized data collection using reliable and accurate tools to capture
      clinically, biologically, psychologically, or socially relevant variables and
      outcomes; and an analysis of data based on survival methods. Interpretation of
      prognostic studies should consider biases related to differential inclusion of
      nonrepresentative samples of patients, poor measurements of outcomes, and poor
      control for confounders. Transferring prognostic results into clinical practice
      should be based on estimates of the predictive performance of models and on a
      demonstration that patient outcomes can be improved by the use of prediction
      rules. 

PMID- 24581917
TI  - Effect of dose and route of immunisation on the immune response induced in cattle
      by heterologous Bacille Calmette-Guerin priming and recombinant adenoviral vector
      boosting.
AB  - BCG is used experimentally as a vaccine against tuberculosis (TB), induced by
      Mycobacterium bovis, in cattle (bTB). However, the efficacy of BCG is variable in
      humans, cattle and guinea pigs. An adenoviral vector expressing Antigen 85A
      (Ad5Ag85A) has enhanced protection against TB in mice when used in combination
      with BCG for prime-boost experiments. However, the route of immunisation affects
      the degree of protection seen. This work examines the immunogenicity of a new
      vectored vaccine (Ad5-TBF) that expresses Ag85A, Rv0287, Rv0288 and Rv0251c to
      explore the effects of dose of adenoviral boost and route of inoculation on
      immunogenicity. We found that 2*10(9) infectious units (iu) delivered
      intradermally conferred the most consistent and strongest responses of the
      different regimes tested. 

PMID- 24581918
TI  - Evaluation of nicotine and cotinine analogs as potential neuroprotective agents
      for Alzheimer's disease.
AB  - The currently available therapies for Alzheimer's disease (AD) and related forms
      of dementia are limited by modest efficacy, adverse side effects, and the fact
      that they do not prevent the relentless progression of the illness. The purpose
      of the studies described here was to investigate the neuroprotective effects of
      the nicotine metabolite cotinine as well as a small series of cotinine and
      nicotine analogs (including stereoisomers) and to compare their effects to the
      four clinically prescribed AD therapies. 

PMID- 24581920
TI  - Preventable coronary heart disease events from control of cardiovascular risk
      factors in US adults with diabetes (projections from utilizing the UKPDS risk
      engine).
AB  - Type 2 diabetes mellitus (T2DM) carries significant risks for coronary heart
      disease (CHD). We examined the potential US population impact of single and
      composite risk factor control. Among US adults with diagnosed T2DM aged>=30 years
      in the National Health and Nutrition Examination Survey 2007 to 2012, we assessed
      CHD events preventable using the United Kingdom Prospective Diabetes Study CHD
      risk engine. We examined in all those not at goal the impact of statistical
      control of smoking, glycated hemoglobin, systolic blood pressure, and total and
      high-density lipoprotein cholesterol, according to the predefined criteria
      setting risk factors at different levels of control representing (1) "All to
      Goal," (2) at "Nominal Control," or (3) at "Aggressive Control." Preventable CHD
      events represented the difference between the number of events estimated from the
      control of these risk factors versus current levels of the risk factors. Of 606
      men (representing 6.2 million) and 603 women (6.3 million) with DM and no
      previous CHD, 1.3 million men and 0.7 million women would develop a CHD event
      within 10 years if left uncontrolled. Controlling all risk factors to goal was
      projected to prevent 35% and 45% of CHD events in men and women, respectively.
      Nominal risk factor control was projected to prevent 36% and 38% and aggressive
      control 51% and 61% of CHD events, respectively. In conclusion, a significant
      proportion of CHD events in adults with T2DM could be prevented from composite
      control of risk factors often not at goal.

PMID- 24581919
TI  - Enhanced potency of the metalloprotease inhibitor TAPI-2 by multivalent display.
AB  - Metalloproteases regulate a vast array of critical cellular processes such as
      proliferation, migration, repair, and invasion/metastasis. In so doing,
      metalloproteases have been shown to play key roles in the pathogenesis of
      multiple disorders including arteriosclerosis, arthritis, cancer metastasis, and
      ischemic brain injury. Therefore, much work has focused on developing
      metalloprotease inhibitors to provide a potential therapeutic benefit against the
      progression of these and other diseases. In order to produce a more potent
      inhibitor of metalloproteases, we synthesized multivalent displays of a
      metalloprotease inhibitor derived from the ring-opening metathesis polymerization
      (ROMP). Specifically, multivalent ligands of a broad-spectrum metalloprotease
      inhibitor, TAPI-2, were generated upon conjugation of the amine-bearing inhibitor
      with the ROMP-derived N-hydroxysuccinimide ester polymer. By monitoring the
      metalloprotease dependent cleavage of the transmembrane protein Semaphorin4D
      (Sema4D), we demonstrated an enhancement of inhibition by multivalent TAPI-2
      compared to monovalent TAPI-2. To further optimize the potency of the multivalent
      inhibitor, we systematically varied the polymer length and inhibitor ligand
      density (mole fraction, chi). We observed that while ligand density plays a
      modest role in the potency of inhibition caused by the multivalent TAPI-2
      display, the length of the polymer produces a much greater effect on inhibitor
      potency, with the shortest polymer achieving the greatest level of inhibition.
      These findings validate the use of multivalent display to enhance the potency of
      metalloprotease inhibitors and further, suggest this may be a useful approach to
      enhance potency of other small molecule towards their targets. 

PMID- 24581921
TI  - An echocardiographic measurement of superior vena cava to inferior vena cava
      distance in patients<20 years of age with idiopathic dilated cardiomyopathy.
AB  - In normal pediatric echocardiograms, the distance from the junction of superior
      vena cava (SVC) and right atrium to inferior vena cava (IVC) and right atrium is
      linearly related to height. We examine this relation in children listed for heart
      transplant with idiopathic dilated cardiomyopathy (IDC) compared with the
      previously defined normal distribution of SVC-IVC to improve matching of heart
      sizes. Measurements of SVC-IVC and left ventricular end-diastolic diameter in 55
      pediatric patients with IDC were correlated with height, weight, and body surface
      area. Regression analyses were performed to find the best-fit equation and
      correlation coefficient. Generalized linear modeling compared SVC-IVC in patients
      with IDC with normal SVC-IVC values from 254 patients. There was a strong linear
      relation in patients with IDC between SVC-IVC and height (R2=0.84) and a
      logarithmic relation to weight (R2=0.80). Left ventricular end-diastolic diameter
      did not correlate with SVC-IVC or any other parameter. In 87% of patients with
      IDC, SVC-IVC was over 2 SDs above predicted normal values (mean z-score=4.3+/
      2.1). In conclusion, predicted SVC-IVC in patients with IDC was different from
      published norms (p<0.001). SVC-IVC in pediatric patients with IDC, although
      linearly related to height, is consistently above normal values.

PMID- 24581922
TI  - Comparison of results of transcatheter aortic valve implantation in patients with
      severely stenotic bicuspid versus tricuspid or nonbicuspid valves.
AB  - Data on transcatheter aortic valve implantation (TAVI) for severe bicuspid aortic
      valve (BAV) stenosis and how this compares to that for tricuspid aortic valve
      (TAV) stenosis are limited. Twenty-one consecutive patients with BAV were treated
      with the Edwards or CoreValve bioprosthesis from November 2007 to December 2012
      at San Raffaele Scientific Institute and Clinical Institute S. Ambrogio, Milan,
      Italy. Results were compared with a cohort of patients with TAV (n=447) treated
      with the same bioprostheses over the same period. Procedural 1- and 12-month
      outcomes were examined as defined by the Valve Academic Research Consortium
      criteria. Patients with BAV were younger (76.7+/-7.1 vs 79.8+/-7.4 years, p=0.06)
      and with a larger aortic annulus (25.0+/-1.8 vs 23.6+/-2.1 mm, p=0.01). Device
      success (85.7% vs 94.4%, p=0.10) was lower in patients with BAV. Although the 30
      day composite safety end point (23.8% vs 21.0%, p=0.76) was similar between the 2
      groups, mortality rate at 30 days was higher (14.2% vs 3.6%, p=0.02) in the BAV
      group. Cardiovascular mortality at 1 year did not differ significantly between
      the 2 groups (10.5% vs 7.4%, p=0.62). In conclusion, transcatheter aortic valve
      implantation in high surgical risk patients with severe BAV stenosis appears to
      be feasible with mid-term cardiovascular mortality similar to that for patients
      with TAV. Early survival and device success, however, were lower for patients
      with BAV demonstrating that further studies are required to identify which subset
      of patients with BAV is best suited for transcatheter treatment.

PMID- 24581923
TI  - Risk and the physics of clinical prediction.
AB  - The current paradigm of primary prevention in cardiology uses traditional risk
      factors to estimate future cardiovascular risk. These risk estimates are based on
      prediction models derived from prospective cohort studies and are incorporated
      into guideline-based initiation algorithms for commonly used preventive
      pharmacologic treatments, such as aspirin and statins. However, risk estimates
      are more accurate for populations of similar patients than they are for any
      individual patient. It may be hazardous to presume that the point estimate of
      risk derived from a population model represents the most accurate estimate for a
      given patient. In this review, we exploit principles derived from physics as a
      metaphor for the distinction between predictions regarding populations versus
      patients. We identify the following: (1) predictions of risk are accurate at the
      level of populations but do not translate directly to patients, (2) perfect
      accuracy of individual risk estimation is unobtainable even with the addition of
      multiple novel risk factors, and (3) direct measurement of subclinical disease
      (screening) affords far greater certainty regarding the personalized treatment of
      patients, whereas risk estimates often remain uncertain for patients. In
      conclusion, shifting our focus from prediction of events to detection of disease
      could improve personalized decision-making and outcomes. We also discuss
      innovative future strategies for risk estimation and treatment allocation in
      preventive cardiology. 

PMID- 24581925
TI  - Inclusion of piroxicam in mesoporous phosphate glass-ceramic and evaluation of
      the physiochemical characteristics.
AB  - The mesoporous glass-ceramic (GC) was employed as a carrier to investigate its
      capability for pharmaceutical applications. Piroxicam (PX) as a model drug was
      loaded in the GC by using of solvent evaporation technique. The physicochemical
      properties and morphology of the powders were evaluated employing X-ray powder
      diffractometry (XRPD), differential scanning calorimetry (DSC), Fourier-transform
      infrared spectroscopy (FT-IR), and scanning electron microscopy (SEM). The drug
      adsorption isotherms were assessed as well. Drug release profiles were examined
      by fitting the data to the 10 common kinetic models. The specific surface area,
      Vm (the volume of the N2 adsorbed on the 1g of the GC when the monolayer is
      complete) and the average pore diameter of the GC powder before and after loading
      process were measured by the Brunauer-Emmett-Teller (BET) and Barrett-Joyner
      Halenda (BJH) analysis benefiting N2 adsorption/desorption isotherms. The ideal
      loading of PX in the GC was 41.8%. The average pore diameter for the GC was
      determined to be about 10nm. The Freundlich model was found to be the best
      adsorption isotherm. Decrease of the GC specific surface area and Vm values were
      observed after loading process. Drug release data were best fitted to the Weibull
      model with the shape factor of 0.4-0.7 signifying the Fickian diffusion of PX
      from the GC. Accordingly, the GC could be considered as a suitable adsorbent to
      develop an oral drug delivery system. 

PMID- 24581924
TI  - Comparison of percutaneous coronary intervention (with drug-eluting stents)
      versus coronary artery bypass grafting in women with severe narrowing of the left
      main coronary artery (from the Women-Drug-Eluting stent for LefT main coronary
      Artery disease Registry).
AB  - Women typically present with coronary artery disease later than men with more
      unfavorable clinical and anatomic characteristics. It is unknown whether
      differences exist in women undergoing treatment for unprotected left main
      coronary artery (ULMCA) disease. Our aim was to evaluate long-term clinical
      outcomes in women treated with percutaneous coronary intervention (PCI) with drug
      eluting stents versus coronary artery bypass grafting (CABG). All consecutive
      women from the Drug-Eluting stent for LefT main coronary Artery disease registry
      with ULMCA disease were analyzed. A propensity matching was performed to adjust
      for baseline differences. In total, 817 women were included: 489 (59.8%)
      underwent treatment with PCI with drug-eluting stents versus 328 (40.2%) with
      CABG. Propensity score matching identified 175 matched pairs, and at long-term
      follow-up there were no differences in all-cause (odds ratio [OR] 0.722, 95%
      confidence interval [CI] 0.357 to 1.461, p=0.365) or cardiovascular (OR 1.100,
      95% CI 0.455 to 2.660, p=0.832) mortality, myocardial infarction (MI; OR 0.362,
      95% CI 0.094 to 1.388, p=0.138), or cerebrovascular accident (CVA; OR 1.200, 95%
      CI 0.359 to 4.007, p=0.767) resulting in no difference in the primary study
      objective of death, MI, or CVA (OR 0.711, 95% CI 0.387 to 1.308, p=0.273).
      However, there was an advantage of CABG in major adverse cardiovascular and
      cerebrovascular events (OR 0.429, 95% CI 0.254 to 0.723, p=0.001), driven
      exclusively by target vessel revascularization (OR 0.185, 95% CI 0.079 to 0.432,
      p<0.001). In women with significant ULMCA disease, no difference was observed
      after PCI or CABG in death, MI, and CVA at long-term follow-up.

PMID- 24581926
TI  - Antimicrobial oligo(p-phenylene-ethynylene) film deposited by resonant infrared
      matrix-assisted pulsed laser evaporation.
AB  - The antimicrobial oligomer, oligo(p-phenylene-ethynylene) (OPE), was deposited as
      thin films by resonant infrared matrix-assisted pulsed laser evaporation (RIR
      MAPLE) on solid substrates and exhibited light-induced biocidal activity. The
      biocidal activity of OPE thin films deposited by spin-coating and drop-casting
      was also investigated for comparison. Enhanced bacterial attachment and biocidal
      efficiency of the film deposited by RIR-MAPLE were observed and attributed to
      nanoscale surface topography of the thin film.

PMID- 24581927
TI  - [Is rotation into primary care useful in the geriatric specialist training
      program? Reflections of a resident].

PMID- 24581928
TI  - Electrocardiographic artifact due to a mobile phone mimicking ventricular
      tachycardia.
AB  - A case of electrocardiographic artifact due to mobile a phone mimicking
      ventricular tachycardia was presented. The artifact was discriminated by close
      scrutiny of ECG and was attributed to a mobile phone because it was simultaneous
      with mobile phone game. 

PMID- 24581929
TI  - Presenting efficacy information in direct-to-consumer prescription drug
      advertisements.
AB  - OBJECTIVE: We evaluated whether presenting prescription drug efficacy information
      in direct-to-consumer (DTC) advertising helps individuals accurately report a
      drug's benefits and, if so, which numerical format is most helpful. METHODS: We
      conducted a randomized, controlled study of individuals diagnosed with high
      cholesterol (n=2807) who viewed fictitious prescription drug print or television
      ads containing either no drug efficacy information or efficacy information in one
      of five numerical formats. We measured drug efficacy recall, drug perceptions and
      attitudes, behavioral intentions, and drug risk recall. RESULTS: Individuals who
      viewed absolute frequency and/or percentage information more accurately reported
      drug efficacy than participants who viewed no efficacy information. Participants
      who viewed relative frequency information generally reported drug efficacy less
      accurately than participants who viewed other numerical formats. CONCLUSION:
      Adding efficacy information to DTC ads-both in print and on television-may
      potentially increase an individual's knowledge of a drug's efficacy, which may
      improve patient-provider communication and promote more informed decisions.
      PRACTICE IMPLICATIONS: Providing quantitative efficacy information in a
      combination of formats (e.g., absolute frequency and percent) may help patients
      remember information and make decisions about prescription drugs.

PMID- 24581930
TI  - The unique achievements of Japanese industries in the super-aged society.
AB  - Unique efforts of the Japanese industries in meeting the needs of the super-aged
      society are introduced through their association with International Association
      for Universal Design (IAUD). Considerations are made on how successes were
      brought about, what can be learned as well as what issues should be addressed in
      the future. 

PMID- 24581931
TI  - Supervisory-level interruption recovery in time-critical control tasks.
AB  - This paper investigates the effectiveness of providing interruption recovery
      assistance in the form of an interactive visual timeline of historical events on
      a peripheral display in support of team supervision in time-critical settings. As
      interruptions can have detrimental effects on task performance, particularly in
      time-critical work environments, there is growing interest in the design of tools
      to assist people in resuming their pre-interruption activity. A user study was
      conducted to evaluate the use of an interactive event timeline that provides
      assistance to human supervisors in time-critical settings. The study was
      conducted in an experimental platform that emulated a team of operators and a
      mission commander performing a time-critical unmanned aerial vehicle (UAV)
      mission. The study results showed that providing interruption assistance enabled
      people to recover from interruptions faster and more accurately. These results
      have implications for interface design that could be adopted in similar time
      critical environments such as air-traffic control, process control, and first
      responders.

PMID- 24581932
TI  - The pathology and pathogenesis of experimental severe acute respiratory syndrome
      and influenza in animal models.
AB  - Respiratory viruses that emerge in the human population may cause high morbidity
      and mortality, as well as concern about pandemic spread. Examples are severe
      acute respiratory syndrome coronavirus (SARS-CoV) and novel variants of influenza
      A virus, such as H5N1 and pandemic H1N1. Different animal models are used to
      develop therapeutic and preventive measures against such viruses, but it is not
      clear which are most suitable. Therefore, this review compares animal models of
      SARS and influenza, with an emphasis on non-human primates, ferrets and cats.
      Firstly, the pathology and pathogenesis of SARS and influenza are compared. Both
      diseases are similar in that they affect mainly the respiratory tract and cause
      inflammation and necrosis centred on the pulmonary alveoli and bronchioles.
      Important differences are the presence of multinucleated giant cells and intra
      alveolar fibrosis in SARS and more fulminant necrotizing and haemorrhagic
      pneumonia in H5N1 influenza. Secondly, the pathology and pathogenesis of SARS and
      influenza in man and experimental animals are compared. Host species, host age,
      route of inoculation, location of sampling and timing of sampling are important
      to design an animal model that most closely mimics human disease. The design of
      appropriate animal models requires an accurate pathological description of human
      cases, as well as a good understanding of the effect of experimental variables on
      disease outcome. 

PMID- 24581933
TI  - [Airway management in a patient with Niemann-Pick disease].

PMID- 24581934
TI  - The desirability of an Intensive Care Unit (ICU) clinician-led bereavement
      screening and support program for family members of ICU Decedents (ICU Bereave).
AB  - PURPOSE: Many bereaved family members (FMs) of intensive care unit decedents
      experience symptoms of complicated grief (CG) or social distress, but there is no
      standard screening or follow-up for these individuals. We determined the
      desirability and need for an intensive care unit-based bereavement screening and
      support program for these FMs. METHODS: We surveyed bereaved FMs to measure
      symptoms of CG, prolonged grief disorder, and social difficulties and the desire
      for support; and staff physicians and nurses at 2 teaching hospitals in Toronto,
      Canada, to determine comfort and interest in providing routine bereavement
      support. RESULTS: We could not contact 69% of FMs largely because of inaccuracies
      in the patient record. Of the 64 who were contacted, 32 (50%) agreed to be
      surveyed a mean (SD) of 7.4 (2.2) months after the loss of their relative. Among
      eligible staff, 57 (61%) of 94 completed the questionnaire. Nine (28%) FMs met
      subthreshold criteria for CG or prolonged grief disorder, and 7 (22%) met
      criteria for social distress. Only 10 (31%) had received professional support for
      emotional symptoms, and 2 (6%) received professional assistance for their social
      difficulties. Fifty-eight percent supported routine screening, and 68% wanted to
      receive (or receive more) support. Fifty-five percent of FMs expressed a strong
      willingness to meet with the medical team to review events surrounding the death
      of the patient, which was the type of support that the health care staff were
      most comfortable providing. Most staff (85%) reported providing emotional support
      at the time of death, but few provided any support afterwards. Fifty-six (98%) of
      57 would be willing to support or participate in a formal bereavement screening
      and support program. Respondents cited the need for training and dedicated time
      to carry out such a program. CONCLUSIONS: An ICU-based bereavement screening and
      support program for FMs of ICU decedents is both needed and desirable, although
      there are important needs and barriers. Future studies should evaluate the
      effectiveness for such a program at improving outcomes among bereaved FMs.

PMID- 24581935
TI  - Prediction equation to estimate dead space to tidal volume fraction correlates
      with mortality in critically ill patients.
AB  - OBJECTIVE: The measurement of dead space to tidal volume fraction (Vd/Vt) using
      various methodologies has been shown to be a reliable predictor of mortality in
      critically ill patients. In this study, we evaluated the correlation of a
      validated equation using clinically available information to predict calculation
      of Vd/Vt with clinically relevant outcome parameters in patients requiring
      mechanical ventilation. METHODS: Calculations of Vd/Vt were obtained based upon a
      previously published prediction equation for dead space ventilation fraction:
      Vd/Vt = 0.320 + 0.0106 (Paco2--end-tidal carbon dioxide measurement) + 0.003
      (respiratory rate per minute) + 0.0015 (age in years) on study days 1, 3 to 4, 6
      to 9, and 14 after initiation of mechanical ventilation in adult patients who
      satisfied 1 of the 3 study defined diseases: (1) acute bacterial pneumonia, (2)
      acute respiratory distress syndrome, or (3) cystic fibrosis. RESULTS: Using the
      final/last available time point calculation of Vd/Vt, a significant difference
      was observed between survivors and nonsurvivors both in relation to mean and
      median values (56.5% vs 71.2% and 56.0% vs 65.0%, respectively). In addition,
      sequential analyses of Vd/Vt calculations over time also demonstrated a
      statistically significant difference between survivors and nonsurvivors for days
      6 to 9. CONCLUSION: In this study-specific population of critically ill patients,
      the prediction equation of Vd/Vt using clinically available parameters correlates
      with mortality. In addition, we provide a simple method to estimate Vd/Vt that
      can be potentially applicable to all critically ill intensive care unit patients.

PMID- 24581936
TI  - Association of genotypes and haplotypes of multi-drug transporter genes ABCB1 and
      ABCG2 with clinical response to imatinib mesylate in chronic myeloid leukemia
      patients.
AB  - The introduction and success of imatinib mesylate (IM) has become a paradigm
      shift in chronic myeloid leukemia (CML) treatment. However, the high efficacy of
      IM has been hampered by the issue of clinical resistance that might due to
      pharmacogenetic variability. In the current study, the contribution of three
      common single nucleotide polymorphisms (SNPs) of ABCB1 (T1236C, G2677T/A and
      C3435T) and two SNPs of ABCG2 (G34A and C421A) genes in mediating resistance
      and/or good response among 215 CML patients on IM therapy were investigated.
      Among these patients, the frequency distribution of ABCG2 421 CC, CA and AA
      genotypes were significantly different between IM good response and resistant
      groups (P=0.01). Resistance was significantly associated with patients who had
      homozygous ABCB1 1236 CC genotype with OR 2.79 (95%CI: 1.217-6.374, P=0.01). For
      ABCB1 G2677T/A polymorphism, a better complete cytogenetic remission was observed
      for patients with variant TT/AT/AA genotype, compared to other genotype groups
      (OR=0.48, 95%CI: 0.239-0.957, P=0.03). Haplotype analysis revealed that ABCB1
      haplotypes (C1236G2677C3435) was statistically linked to higher risk to IM
      resistance (25.8% vs. 17.4%, P=0.04), while ABCG2 diplotype A34A421 was
      significantly correlated with IM good response (9.1% vs. 3.9%, P=0.03). In
      addition, genotypic variant in ABCG2 421C>A was associated with a major molecular
      response (MMR) (OR=2.20, 95%CI: 1.273-3.811, P=0.004), whereas ABCB1 2677G>T/A
      variant was associated with a significantly lower molecular response (OR=0.49,
      95%CI: 0.248-0.974, P=0.04). However, there was no significant correlation of
      these SNPs with IM intolerance and IM induced hepatotoxicity. Our results suggest
      the usefulness of genotyping of these single nucleotide polymorphisms in
      predicting IM response among CML patients. 

PMID- 24581937
TI  - Optimising treatment parameters for Radiofrequency Induced Thermal Therapy
      (RFiTT): A comparison of the manufacturer's treatment guidance with a locally
      developed treatment protocol.
AB  - OBJECTIVE: Radiofrequency induced Thermal Therapy (RFiTT) is an established
      endovenous device for the treatment of varicose veins. Our aim was to compare the
      manufacturer's treatment guidance with a locally developed treatment protocol on
      early truncal ablation rates between two patient cohorts. METHODS: The study was
      a retrospective analysis of prospectively collected data from 534 patients
      treated for incompetent truncal saphenous veins between June 2009 and December
      2012. Patients were treated either according to the manufacturer's guidance
      (Treatment 1), a single pullback rate of >=1.5 s/cm, or according to local
      protocol (Treatment 2), repeated vein treatment to visibly occlude the vein
      lumen. Follow-up at 6 weeks and 12 months included duplex examination, assessment
      of complications, and pain scores for the first postoperative week. RESULTS: 14
      patients did not attend follow-up, leaving 98 patients (142 saphenous trunk
      treatments) who received Treatment 1 and 422 patients (566 saphenous trunk
      treatments) who received Treatment 2. The two groups were well matched for age,
      sex, and preoperative vein parameters. Six week occlusion rates were
      significantly different, with more treatment failures after Treatment 1
      (Treatment 1 5.6% vs. Treatment 2 0.9%; p = .0001). Treatment 1 was more likely
      to produce incomplete ablation (3.5% vs. 0.9%) and non-ablation (2.1% vs. 0.0%)
      compared with Treatment 2. No major complications occurred in either group and
      functional outcomes were otherwise comparable between the two treatment methods.
      Longer-term follow-up at 12 months in the first 100 patients undergoing Treatment
      2 demonstrated maintenance of the early advantage, with partial recanalisations
      in 9% and 2% for Treatments 1 and 2, respectively. CONCLUSIONS: Six weeks after
      treatment with RFiTT, a protocol of repeated vein treatments to visibly
      obliterate the vein lumen produced more reliable venous occlusion compared with
      manufacturer's guidance. This advantage is maintained at 12 months.

PMID- 24581938
TI  - Spontaneous delayed sealing in selected patients with a primary type-Ia endoleak
      after endovascular aneurysm repair.
AB  - OBJECTIVE: Direct additional therapy is advised for type-Ia endoleaks detected on
      completion angiography after endovascular aneurysm repair (EVAR). Additional
      intraoperative endovascular procedures are, however, often challenging or not
      possible, and direct open conversion is unattractive. The results of a selective,
      conservative strategy for patients with primary type-Ia endoleak has been
      analysed. METHODS: This was a retrospective, single-centre study (UMC, Utrecht,
      NL). From 2004 to 2008, all patients with a primary type-Ia endoleak and suitable
      anatomy for EVAR, stentgraft oversizing >=15%, and optimal deployment were
      included. Complications during follow-up were studied and all sequential CTA
      scans were reviewed. These were compared with the remaining patients, treated
      during the same period. RESULTS: Fifteen patients were included (14 male, median
      age 77, range 67-85) with a median aneurysm diameter of 60 mm (48-80), an
      aneurysm neck diameter of 26 mm (21-32), a neck length of 29 mm (11-39), and
      infrarenal angulation of 49 degrees  (31-90). One patient suffered rupture 2 days
      after EVAR - leading to the only AAA-related death. Eight of the 15 type-Ia
      endoleaks disappeared spontaneously on the first postoperative CTA, obtained
      within 1 week of EVAR. On the second postoperative CTA, obtained a median of 5
      months (1-12) after EVAR, all remaining endoleaks had sealed. One recurrence
      occurred at 4.85 years. During a median follow-up of 3.3 years, there were five
      secondary interventions. Compared with controls, there were more secondary (or
      recurrent) type-1a endoleaks (13% vs. 4%), endograft migrations (13% vs. 3%), sac
      growths (33% vs. 16%), and secondary interventions (33% vs. 23%). None of these
      differences however, were statistically significant. CONCLUSIONS: All but one of
      the primary type-Ia endoleaks sealed spontaneously. Until sealing, the risk of
      rupture persisted, but subsequently only one recurrence of type-Ia endoleak was
      seen. In selected patients, a conservative approach for primary type-Ia endoleaks
      may be justified.

PMID- 24581939
TI  - The value of randomised trials for prostate cancer management.

PMID- 24581940
TI  - Escalated-dose versus control-dose conformal radiotherapy for prostate cancer:
      long-term results from the MRC RT01 randomised controlled trial.
AB  - BACKGROUND: The aim of this trial was to compare dose-escalated conformal
      radiotherapy with control-dose conformal radiotherapy in patients with localised
      prostate cancer. Preliminary findings reported after 5 years of follow-up showed
      that escalated-dose conformal radiotherapy improved biochemical progression-free
      survival. Based on the sample size calculation, we planned to analyse overall
      survival when 190 deaths occurred; this target has now been reached, after a
      median 10 years of follow-up. METHODS: RT01 was a phase 3, open-label,
      international, randomised controlled trial enrolling men with histologically
      confirmed T1b-T3a, N0, M0 prostate cancer with prostate specific antigen of less
      than 50 ng/mL. Patients were randomly assigned centrally in a 1:1 ratio, using a
      computer-based minimisation algorithm stratifying by risk of seminal vesicle
      invasion and centre to either the control group (64 Gy in 32 fractions, the
      standard dose at the time the trial was designed) or the escalated-dose group (74
      Gy in 37 fractions). Neither patients nor investigators were masked to
      assignment. All patients received neoadjuvant androgen deprivation therapy for 3
      6 months before the start of conformal radiotherapy, which continued until the
      end of conformal radiotherapy. The coprimary outcome measures were biochemical
      progression-free survival and overall survival. All analyses were done on an
      intention-to-treat basis. Treatment-related side-effects have been reported
      previously. This trial is registered, number ISRCTN47772397. FINDINGS: Between
      Jan 7, 1998, and Dec 20, 2001, 862 men were registered and 843 subsequently
      randomly assigned: 422 to the escalated-dose group and 421 to the control group.
      As of Aug 2, 2011, 236 deaths had occurred: 118 in each group. Median follow-up
      was 10.0 years (IQR 9.1-10.8). Overall survival at 10 years was 71% (95% CI 66
      75) in each group (hazard ratio [HR] 0.99, 95% CI 0.77-1.28; p=0.96). Biochemical
      progression or progressive disease occurred in 391 patients (221 [57%] in the
      control group and 170 [43%] in the escalated-dose group). At 10 years,
      biochemical progression-free survival was 43% (95% CI 38-48) in the control group
      and 55% (50-61) in the escalated-dose group (HR 0.69, 95% CI 0.56-0.84;
      p=0.0003). INTERPRETATION: At a median follow-up of 10 years, escalated-dose
      conformal radiotherapy with neoadjuvant androgen deprivation therapy showed an
      advantage in biochemical progression-free survival, but this advantage did not
      translate into an improvement in overall survival. These efficacy data for
      escalated-dose treatment must be weighed against the increase in acute and late
      toxicities associated with the escalated dose and emphasise the importance of use
      of appropriate modern radiotherapy methods to reduce side-effects. FUNDING: UK
      Medical Research Council.

PMID- 24581942
TI  - Determination of insulin resistance in surgery: the choice of method is crucial.
AB  - BACKGROUND & AIMS: In elective surgery, postoperative hyperglycaemia and insulin
      resistance are independent risk factors for complications. Since the simpler HOMA
      method has been used as an alternative to the hyperinsulinemic normoglycemic
      clamp in studies of surgery induced insulin resistance, we compared the two
      methods in patients undergoing elective surgery. METHODS: Data from 113 non
      diabetic patients undergoing elective surgery were used. Insulin sensitivity,
      both before and after surgery, was quantified by the clamp and HOMA. Pre- and
      postoperatively, the results of the clamp were compared to HOMA using regression-
      and correlation analysis. Degree of agreement between the methods was studied
      using weighted linear kappa and the Bland-Altman test. RESULTS: Both the clamp
      and HOMA recorded a mean relative reduction in insulin sensitivity of 39 +/- 24%
      and 39 +/- 61% respectively after surgery; with significant correlations (p <
      0.01) for pre- and post-operative measures as well as for relative changes.
      However r(2) values were low: 0.04, 0.07 and 0.03 respectively. The degree of
      agreement for the relative change in insulin sensitivity using the Bland-Altman
      test gave a mean of difference 0% but "limits of agreement" (+/- 2SD) was +/-
      125%. This poor inter-method agreement was consolidated by a weighted linear
      kappa value of 0.18. CONCLUSION: While the hyperinsulinemic euglycemic clamp
      measures the postoperative changes in insulin sensitivity, HOMA measures
      something different. Data using the HOMA method must therefore be interpreted
      cautiously and is not interchangeable with data obtained from the clamp.

PMID- 24581941
TI  - AIDS-related mycoses: the way forward.
AB  - The contribution of fungal infections to the morbidity and mortality of HIV
      infected individuals is largely unrecognized. A recent meeting highlighted
      several priorities that need to be urgently addressed, including improved
      epidemiological surveillance, increased availability of existing diagnostics and
      drugs, more training in the field of medical mycology, and better funding for
      research and provision of treatment, particularly in developing countries. 

PMID- 24581943
TI  - Plasminogen activator inhibitor-1 (PAI-1) in children and adolescents with type 1
      diabetes mellitus: relation to diabetic micro-vascular complications and carotid
      intima media thickness.
AB  - BACKGROUND: Plasminogen activator inhibitor-1 (PAI-1) is a fast-acting inhibitor
      of fibrinolysis that has been linked to increase risk of thrombosis. We
      determined PAI-1 levels in 80 children and adolescents with type 1 diabetes
      (T1DM) compared with 40 healthy controls as a potential marker for micro-vascular
      complications and assessed the relation to carotid intima media thickness (CIMT)
      as a synergistic risk factor for development of atherosclerosis. METHODS:
      Patients were divided into 2 groups according to micro-vascular complications.
      Hemoglobin A1c (HbA1c), urinary albumin excretion, fasting serum lipid profile
      and PAI-1 levels were measured. CIMT of the common carotid artery was assessed
      using high resolution ultrasonography. RESULTS: PAI-1 levels were significantly
      elevated in the group with diabetes compared with control group (p<0.001). PAI-1
      levels were also increased in patients with micro-vascular complications compared
      with those without (p<0.001). CIMT was significantly higher in patients,
      particularly those with micro-vascular complications than patients without
      complications or controls (p<0.001). Positive correlations were found between PAI
      1 levels and random blood glucose, HbA1c, triglycerides, total cholesterol and
      CIMT (p<0.05). CONCLUSIONS: Increased plasma PAI-1 may be involved in the state
      of hypofibrinolysis in patients with T1DM leading to the occurrence of micro
      vascular complications and increased risk of atherosclerosis.

PMID- 24581944
TI  - Race/ethnicity and measures of glycaemia in the year after diagnosis among youth
      with type 1 and type 2 diabetes mellitus.
AB  - AIMS: To assess associations between race/ethnicity, glycated hemoglobin (HbA1c),
      and glycemic control among youth with type 1 (T1D) or type 2 diabetes (T2D).
      METHODS: The study sample was youth<20years old from the SEARCH California Center
      diagnosed from 2002 to 2009 who remained insured for at least one year. HbA1c at
      one year was from clinical data; HbA1c at diagnosis was from clinical data (81%)
      or imputed (19%). Multivariable logistic and linear regression models were used
      to examine associations between race/ethnicity and poor glycemic control
      (>=9.5%), HbA1c at one-year, and change in HbA1c. RESULTS: The study included
      1162 Hispanic (52.3%), non-Hispanic White (NHW, 28.4%), African American (15.1%)
      and Asian/Pacific Islander (4.1%) youth. Among T1D youth (n=789), Hispanics were
      1.60 times as likely (95% CI 1.01-2.53) to have poor control at one year compared
      to NHWs, after adjustments. Among T2D youth (n=373), only African American youth
      were significantly more likely (OR=4.85; 95% CI 1.49-15.77) to have poor control
      at one year, after adjustments. HbA1c at one year and change in HbA1c did not
      differ by race/ethnicity. CONCLUSION: Poor glycemic control was evident one year
      after diagnosis in some minority youth with T1D or T2D in an integrated managed
      health care setting.

PMID- 24581945
TI  - Redox proteins and radiotherapy.
AB  - Although conventional radiotherapy can directly damage DNA and other organic
      molecules within cells, most of the damage and the cytotoxicity of such ionising
      radiation, comes from the production of ions and free radicals produced via
      interactions with water. This 'indirect effect', a form of oxidative stress, can
      be modulated by a variety of systems within cells that are in place to, in normal
      situations, maintain homeostasis and redox balance. If cancer cells express high
      levels of antioxidant redox proteins, they may be more resistant to radiation and
      so targeting such systems may be a profitable strategy to increase therapeutic
      efficacy of conventional radiotherapy. An overview, with exemplars, of the main
      systems regulating redox homeostasis is supplied and discussed in relation to
      their use as prognostic and predictive biomarkers, and how targeting such
      proteins and systems may increase radiosensitivity and, potentially, improve the
      radiotherapeutic response. 

PMID- 24581946
TI  - Selective targeting of the G2/M cell cycle checkpoint to improve the therapeutic
      index of radiotherapy.
AB  - Despite tremendous advances in radiotherapy techniques, allowing dose escalation
      to tumour tissues and sparing of organs at risk, cure rates from radiotherapy or
      chemoradiotherapy remain suboptimal for most cancers. In tandem with our growing
      understanding of tumour biology, we are beginning to appreciate that targeting
      the molecular response to radiation-induced DNA damage holds great promise for
      selective tumour radiosensitisation. In particular, approaches that inhibit cell
      cycle checkpoint controls offer a means of exploiting molecular differences
      between tumour and normal cells, thereby inducing so-called cancer-specific
      synthetic lethality. In this overview, we discuss cellular responses to radiation
      induced damage and discuss the potential of using G2/M cell cycle checkpoint
      inhibitors as a means of enhancing tumour control rates. 

PMID- 24581947
TI  - Value of clinical pulmonary infection score in critically ill children as a
      surrogate for diagnosis of ventilator-associated pneumonia.
AB  - RATIONALE: Although the modified clinical pulmonary infection score (mCPIS) has
      been endorsed by national organizations, only a very few pediatric studies have
      assessed it for the diagnosis of ventilator-associated pneumonia (VAP). METHODS:
      Seventy children were prospectively included if they fulfilled the diagnosis
      criteria for VAP referenced by the Centers for Disease Control and Prevention.
      The primary outcome was performance of mCPIS calculated on day 1 to accurately
      identify VAP as defined by microbiological data. RESULTS: The data showed that an
      mCPIS of 6 or higher had a sensitivity of 94%, specificity of 50%, positive
      predictive value of 64%, negative predictive value of 90%, a positive likelihood
      ratio of 1.88, and a negative likelihood ratio of 0.11. The area under the
      receiver operating characteristic curve was 0.70. A positive posttest result
      increased the disease probability by 15.4%, whereas a negative test result
      reduced the probability by 38.6%. Patients with an mCPIS of 6 or higher had
      longer length of mechanical ventilation and pediatric intensive care unit stay
      compared with patients with an mCPIS lower than 6. CONCLUSION: The mCPIS had a
      clinically acceptable performance, and it can be a helpful screening tool for VAP
      diagnosis. An mCPIS lower than 6 was highly able in distinguishing patients
      without VAP. Despite its high sensitivity and negative predictive value of this
      score, further studies are required to assess the use of mCPIS in guiding
      therapeutic decisions.

PMID- 24581948
TI  - Association between sympathoadrenal activation, fibrinolysis, and endothelial
      damage in septic patients: a prospective study.
AB  - PURPOSE: The purpose of this study is to investigate potential associations
      between sympathoadrenal activation and/or vasopressor/inotropic therapy and
      endothelial activation, damage, and coagulopathy in septic patients. MATERIALS
      AND METHODS: Septic patients included in the Scandinavian Starch for Severe
      Sepsis/Septic Shock trial who were expected not to receive catecholamines at
      screening preintervention (baseline) and had baseline blood sampled. Clinical,
      outcome data, and measurements of plasma concentration (p-) biomarkers reflecting
      sympathoadrenal activation, endothelial activation and damage, natural
      anticoagulation, fibrinolysis, cell damage, and platelet activation. RESULTS:
      Sixty-seven patients were included, of whom 14 turned out to receive
      noradrenaline infusion at blood sampling. These 14 patients had p-noradrenaline 5
      fold higher than patients not receiving catecholamines (n=53), whereas no other
      baseline preintervention biomarkers differed. In the 53 patients not receiving
      catecholamines at blood sampling, endogenous p-noradrenaline correlated
      positively with adrenaline, syndecan 1, soluble vascular endothelial growth
      factor receptor 1, soluble CD40 ligand, tissue-type plasminogen activator, and
      plasminogen activator inhibitor 1 (PAI-1) and negatively with PAI-1/tissue-type
      plasminogen activator ratio (all P<.05) and was independently associated with
      syndecan 1, soluble vascular endothelial growth factor receptor 1, and PAI-1 (all
      P<.05), and 28- and 90-day mortality (P<.05). CONCLUSIONS: In septic patients,
      endogenous noradrenaline was independently associated with biomarkers of
      endothelial activation, damage, fibrinolysis and mortality, comparable with
      findings in trauma and myocardial infarction patients. The catecholamine surge in
      critical illness may contribute to balance endothelial damage and procoagulation
      with hypocoagulability and hyperfibrinolysis in the circulating blood.

PMID- 24581949
TI  - Critically ill elderly patients in a developing world--mortality and functional
      outcome at 1 year: a prospective single-center study.
AB  - PURPOSE: To study the mortality and outcome of critically ill elderly patients in
      a developing country with focus on nutritional and socioeconomic status. METHODS:
      A prospective study of 109 patients (215 screened) admitted consecutively to the
      intensive care unit from 2011 to 2012. Demographics, Acute Physiology and Chronic
      Health Evaluation (APACHE) II score, mechanical ventilation, Malnutrition
      Universal Screening Tool score, socioeconomic category, functional status,
      delirium, and length of stay were recorded. Telephonic assessment of outcome was
      done at 1 year. Appropriate statistical tests compared differences between
      subgroups. Multivariate analysis was performed on significant variables (P<.1)
      affecting mortality. RESULTS: At 12 months after discharge, 46.8% of patients
      (mean age, 76.5+/-9.6 years; APACHEII, 22.7+/-6.4; and intensive care unit stay,
      7.8+/-3.4 days) had died. Risk factors for mortality at 12 months were APACHE II
      score (P<.001; odds ratio [OR], 1.2; 95% confidence interval [CI], 1.1-1.3),
      severe malnutrition (P=.006; OR, 0.08; 95% CI, 0.01-0.48), and delirium (P=.03;
      OR, 0.32; 95% CI, 0.11-0.9). Risk factors for short-term mortality (at 28 days)
      were APACHE II score (P=.02; OR, 1.1 [1.0-1.2]) and premorbid functional status
      (P=.03; OR, 0.2 [0.1-0.8]). Kaplan-Meier survival analysis showed a significant
      association with malnutrition (log-rank test, P=.012) but not with socioeconomic
      category. Most (72%) of the survivors had a favorable functional status.
      CONCLUSIONS: Malnutrition, delirium, and APACHEII were risk factors for long-term
      mortality. Survivors had a good functional outcome. Appropriate quality of life
      tools for this population need to be developed.

PMID- 24581950
TI  - The ability of current scoring systems in differentiating transient and
      persistent organ failure in patients with acute pancreatitis.
AB  - PURPOSE: The purpose of this study is to investigate the accuracy of currently
      used scoring systems in differentiating transient and persistent organ failure in
      patients with acute pancreatitis (AP). MATERIALS AND METHODS: In this
      retrospective study, 127 consecutive patients with AP and organ failure were
      included. Patients were divided into transient and persistent organ failure
      groups. The Acute Physiology and Chronic Health Examination II score, bedside
      index of severity in acute pancreatitis, harmless acute pancreatitis score, and
      modified Marshall scores within the first 24 hours of organ failure were
      collected, and their accuracy in predicting transient organ failure was assessed.
      RESULTS: Transient organ failure occurred in 46 patients (36.2%). Fewer patients
      with transient organ failure initiated with multiple organ failure (13.0% vs
      37.0%, P=.004) and renal failure (17.4% vs 44.4%, P=.002). In predicting
      transient organ failure, the area under the curves of the 4 scoring systems is
      from 0.66 to 0.71. The area under the curve of serum amylase was 0.78, which was
      slightly better than that of the modified Marshall and Acute Physiology and
      Chronic Health Examination II score and was significantly better than that of the
      bedside index of severity in acute pancreatitis and harmless acute pancreatitis
      score (P<.05). CONCLUSIONS: Current scoring systems are not accurate enough in
      differentiating transient and persistent organ failure in patients with AP.

PMID- 24581951
TI  - Autonomic nervous system and inflammation.

PMID- 24581952
TI  - A granulomatous chronic disease.

PMID- 24581953
TI  - Response re: 'Autologous fat grafting for the treatment of velopharyngeal
      insufficiency: state of the art'.

PMID- 24581954
TI  - Analysis of multiple risk factors affecting the result of free flap transfer for
      necrotising soft tissue defects of the lower extremities in patients with type 2
      diabetes mellitus.
AB  - BACKGROUND: The limb-threatening large soft tissue defects that occur on the feet
      of type 2 diabetic patients have complex causes and are less likely to be
      corrected by free flap reconstruction compared to those in non-diabetic patients.
      We retrospectively analysed factors affecting the success of free flap transfer
      for necrotising soft tissue defects of the lower extremities in patients with
      type 2 diabetes. METHODS: This study included 33 diabetic patients whose feet
      were treated with free flap transfers. All patients had limb-threatening large
      soft tissue defects with tendon or bone exposure. The operative results were
      divided into three groups at 1 month post-operatively: the complete healing
      group, and the complication group, with either partial necrosis requiring
      additional simple procedures or flap failure with total necrosis. Nine
      preoperative factors were analysed: (1) ankle brachial index, (2) HbA1c, (3) BMI,
      (4) the smoking factor, (5) atherosclerotic calcifications (6) serum creatinine
      levels (>1.28 mg dL(-1) vs. <1.28 mg dL(-1)), (7) GFR, (8) wound infection and
      (9) wound defect size. RESULTS: Of the 33 patients, 15 showed complete healing
      and 18 showed complications of the free flap (eight partial necrosis and 10 flap
      failure). No atherosclerotic calcifications were found in the patients in the
      complete healing group, although they were found in 12 patients in the
      complication group, and this difference was significant (p = 0.002). Patients
      with serum creatinine levels >1.28 mg dL(-1) had significantly higher free flap
      transfer complication rates than those with serum creatinine levels <1.28 mg dL(
      1) (p = 0.038). CONCLUSIONS: This study analysed the risk factors of free flap
      reconstruction for limb-threatening large soft tissue defects on the feet of type
      2 diabetic patients. Serum creatinine levels >1.28 mg dL(-1) and atherosclerotic
      calcifications were confirmed as risk factors for flap survival.

PMID- 24581955
TI  - Influence of fat/carbohydrate ratio on progression of fatty liver disease and on
      development of osteopenia in male rats fed alcohol via total enteral nutrition
      (TEN).
AB  - Alcohol abuse is associated with the development of fatty liver disease and also
      with significant osteopenia in both genders. In this study, we examined ethanol
      induced pathology in response to diets with differing fat/carbohydrate ratios.
      Male Sprague-Dawley rats were fed intragastrically with isocaloric liquid diets.
      Dietary fat content was either 5% (high carbohydrate, HC) or 45% (high fat, HF),
      with or without ethanol (12-13 g/kg/day). After 14, 28, or 65 days, livers were
      harvested and analyzed. In addition, bone morphology was analyzed after 65 days.
      HC rats gained more weight and had larger fat pads than HF rats with or without
      ethanol. Steatosis developed in HC + ethanol (HC + EtOH) compared to HF + ethanol
      (HF + EtOH) rats, accompanied by increased fatty acid (FA) synthesis and
      increased nuclear carbohydrate response element binding protein (ChREBP) (p <
      0.05), but in the absence of effects on hepatic silent mating type information
      regulation 2 homolog (SIRT-1) or nuclear sterol regulatory binding element
      protein (SREBP-1c). Ethanol reduced serum leptin (p < 0.05) but not adiponectin.
      Over time, HC rats developed fatty liver independent of ethanol. FA degradation
      was significantly elevated by ethanol in both HC and HF groups (p < 0.05). HF +
      EtOH rats had increased oxidative stress from 28 days, increased necrosis
      compared to HF controls and higher expression of cytochromes P450, CYP2E1, and
      CYP4A1 compared to HC + EtOH rats (p < 0.05). In contrast, HC + EtOH rats had no
      significant increase in oxidative stress until day 65 with no observed increase
      in necrosis. Unlike liver pathology, no dietary differences were observed on
      ethanol-induced osteopenia in HC compared to HF groups. These data demonstrate
      that interactions between diet composition and alcohol are complex, dependent on
      the length of exposure, and are an important influence in development of fatty
      liver injury. Importantly, it appears that diet composition does not affect
      alcohol-associated skeletal toxicity. 

PMID- 24581956
TI  - Impact of flexible insulin therapy on blood glucose variability, oxidative stress
      and inflammation in type 1 diabetic patients: the VARIAFIT study.
AB  - AIMS: HbA1c only partially predicts vascular risk in patients with type 1
      diabetes (T1D), and a role for blood glucose variability (BGV) is a matter of
      debate. For this reason, this study investigated the impact of an educational
      programme of flexible insulin therapy (FIT) on BGV and oxidative stress. METHODS:
      Tests were conducted on 30 adult T1D patients in a prospective, single-centre
      trial at baseline (M0), and at 3 and 6 months (M3 and M6, respectively) of the
      FIT programme to determine BGV, as reflected by mean amplitude of glycaemic
      excursions (MAGE), low blood glucose index (LBGI), lability index (LI), average
      daily risk range (ADRR), glycaemic lability (scored by two diabetologists),
      urinary leukotriene E4 (LTE4), 11-dehydro-thromboxane B2 (TXB2) and 8-iso
      prostaglandin F2alpha (PGF2). RESULTS: HbA1c (7.7 +/- 0.9%), ADRR, MAGE, LBGI and
      LI did not change from M0 to M3 and M6, although ADRR and LBGI significantly
      improved at M3 and M6 in patients with the highest baseline indices (>= 40 and >=
      5, respectively). TXB2 declined at M6 (832 +/- 625 vs. 633 +/- 972 pg/mg;
      P=0.048), whereas LTE4 and PGF2 remained stable. ADRR showed the strongest
      correlation with glycaemic lability scores at all visits (r>=0.84, P<0.0001).
      CONCLUSION: A FIT educational programme improved BGV only in patients with the
      highest baseline variability, and led to no changes in HbA1c, while ADRR closely
      correlated with glycaemic lability score. Our data do not support a relationship
      between BGV and oxidative stress in T1D patients, although the impact of
      variability on TXB2 deserves further investigation (ClinicalTrials.gov
      NCT00973492).

PMID- 24581958
TI  - Differentiation of infiltrative cholangiocarcinoma from benign common bile duct
      stricture using three-dimensional dynamic contrast-enhanced MRI with MRCP.
AB  - AIM: To retrospectively evaluate the criteria for discriminating infiltrative
      cholangiocarcinoma from benign common bile duct (CBD) stricture using three
      dimensional dynamic contrast-enhanced (3D-DCE) magnetic resonance imaging (MRI)
      combined with magnetic resonance cholangiopancreatography (MRCP) imaging and to
      determine the predictors for cholangiocarcinoma versus benign CBD stricture.
      MATERIALS AND METHODS: 3D-DCE MRI and MRCP images in 28 patients with
      infiltrative cholangiocarcinoma and 23 patients with benign causes of CBD
      stricture were reviewed retrospectively. The final diagnosis was based on
      surgical or biopsy records. Two radiologists analysed the MRI images for
      asymmetry, including the wall thickness, length, and enhancement pattern of the
      narrowed CBD segment, and upstream CBD dilatation. MRI findings that could be
      used as predictors were identified by univariate analysis and multivariable
      stepwise logistic regression analysis. RESULTS: Malignant strictures were
      significantly thicker (4.4 +/- 1.2 mm) and longer (16.7 +/- 7.7 mm) than the
      benign strictures (p < 0.05), and upstream CBD dilatation was larger in the
      infiltrative cholangiocarcinoma cases (20.7 +/- 5.7 mm) than in the benign cases
      (16.5 +/- 5.2 mm; p = 0.018). During both the portal venous and equilibrium
      phases, hyperenhancement was more frequently observed in malignant cases than in
      benign cases (p < 0.001). The results of the multivariable stepwise logistic
      regression analysis showed that both hyperenhancement of the involved CBD during
      the equilibrium phase and the ductal thickness were significant predictors for
      malignant strictures. When two diagnostic predictive values were used in
      combination, almost all patients with malignant strictures (n = 26, 92.9%) and
      benign strictures (n = 21, 91.3%) were correctly identified; the overall accuracy
      was 92.2% with correct classifications in 47 of the 51 patients. CONCLUSION:
      Infiltrative cholangiocarcinoma and benign CBD strictures could be effectively
      differentiated using DCE-MRI and MRCP based on hyperenhancement during the
      equilibrium phase and bile wall thickness of the involved segment.

PMID- 24581959
TI  - Selective internal radiation therapy of hepatic tumours: is coiling of the
      gastroduodenal artery always beneficial?
AB  - AIM: To assess the effect of gastroduodenal artery (GDA) occlusion prior to
      selective internal radiation therapy (SIRT) with regards to arterial hepato
      intestinal collateralization (HIC). MATERIALS AND METHODS: Six hundred and six
      patients were scheduled for SIRT between 2006 and 2012 at University Hospital
      Essen, Germany. Digital subtraction angiography (DSA) followed by administration
      of 99m-technetium labelled human serum albumin microspheres ((99m)Tc-HSAM) and
      single-photon emission computed tomography combined with computed tomography
      (SPECT/CT) was initially performed. Depending on vascular anatomy and hepatic
      tumour load, GDA coil embolization was considered. In subsequent (99m)Tc-HSAM
      rescans or therapeutic DSA, HIC and its consequences for SIRT were analysed.
      RESULTS: The GDA was occluded in 86 of 606 patients (14%). Twenty-two of these 86
      patients did not undergo SIRT due to the patients' clinical status or SIRT
      contraindications. In 28 of the remaining 64 patients, newly apparent or reopened
      HIC were seen either at the site of the proximal GDA (n = 21) or in the periphery
      of the hepatic arteries (n = 7). In 25 of these 28 patients, the HIC could be
      occluded or the catheter position could be changed achieving a safe (90)Y
      application. However, due to the newly visible HIC in three of 28 patients, SIRT
      was regarded as unsafe and was abandoned. CONCLUSION: Coil embolization of the
      GDA may induce arterial hepato-intestinal collaterals. Although most of these
      collaterals do not impede (90)Y administration, SIRT may become unfeasible in
      specific occasions. Hence, segmental or lobar SIRT instead of a whole-liver
      approach with coiling of the GDA is recommended.

PMID- 24581960
TI  - Maximizing the clinical benefit of high-pitch, single-heartbeat CT coronary
      angiography in clinical practice.
AB  - AIM: To prospectively analyse the occurrence of right coronary artery (RCA)
      artefact and assess its relationship with patient heart rate (HR) and HR
      variability (HRV) in order to determine the most appropriate parameters for high
      pitch cardiovascular computed tomography (CT) acquisition, minimize the
      likelihood of artefact, and maximize the clinical benefit in consecutive clinical
      high-pitch CT coronary angiography (CA) examinations. MATERIALS AND METHODS: One
      hundred and seventy-three patients undergoing high-pitch CTCA were prospectively
      assessed for the presence of RCA artefact. Median and maximum HR and the
      difference in predicted and actual acquisition HR (HR difference, HRD) were
      correlated from the electrocardiograms recorded at the time of acquisition.
      RESULTS: Sixty-six percent of the cohort was male, with a median age of 54 (range
      16-84 years). There were 53 cases of RCA artefact (30.6%); 26 (49.1%) of these
      required further imaging to fully delineate the RCA. Of the 53 cases with
      artefact, 81.1% affected the distal RCA and 18.9% were more proximal. Gender was
      not associated with an increased likelihood of the artefact (p = 0.14). RCA
      artefact decreased by 2% with each year of increasing age (p = 0.04). When
      compared with a reference HR of >70 beats/min, univariate analysis demonstrated
      RCA artefact significantly increased with both increasing median and maximum HR,
      whilst the incidence of RCA artefact increased for all HRD >1, with a greater
      likelihood of artefact with increasing HRD. CONCLUSION: The present results
      highlight the importance of optimizing patient HR in order to reduce the
      likelihood of RCA artefact. In addition to aggressive HR control to a median HR
      of <=60 beats/min, the present results suggest limiting high-pitch acquisition to
      patients with HR variability of <3 beats/min. Therefore, use of beta-blockers is
      of crucial importance to both reduce HR and HR variability to optimize use of
      high-pitch single-heartbeat CTCA.

PMID- 24581961
TI  - Emergency computed tomography for acute pelvic trauma: where is the bleeder?
AB  - Contrast medium extravasation at computed tomography (CT) is an accurate
      indicator of active haemorrhage in pelvic trauma. When this is present,
      potentially lifesaving surgical or endovascular treatment should be considered.
      Identification of the site or territory of haemorrhage is helpful for the
      interventional radiologist as it allows for focused angiographic evaluation and
      expedites haemostatic angio-embolisation. Even with thin-section arterial phase
      CT, tracing the bleeding vessel is not always possible and is often time
      consuming. We introduce a technique for predicting the bleeding vessel based on
      knowledge of the cross-sectional anatomical territory of the vessel as an
      alternative to tracing the vessel's course. Several case examples with digital
      subtraction angiography (DSA) correlation will be provided. 

PMID- 24581962
TI  - Transcatheter arterial chemoembolization combined with radiofrequency ablation
      can improve survival of patients with hepatocellular carcinoma with portal vein
      tumour thrombosis: extending the indication for ablation?
AB  - AIM: To retrospectively assess long-term survival benefit and safety of
      transcatheter arterial chemoembolization (TACE) combined with radiofrequency
      ablation (RFA) in hepatocellular carcinoma (HCC) patients with portal vein tumour
      thrombosis (PVTT), and to evaluate factors that significantly affect outcomes of
      these patients. MATERIALS AND METHODS: One hundred and thirty-four HCC patients
      (118 men and 16 women; mean age 54.8 years, range 26-79 years) with PVTT were
      retrospectively assessed. Patients were treated with TACE combined with RFA. Data
      analysed included patient demographics, liver volume, Child-Pugh score, and
      Cancer of the Liver Italian Programme (CLIP) score and imaging findings. Survival
      time (from occurrence of PVTT to last follow-up) was calculated using the Kaplan
      Meier method, predictive factors and its correlation with survival was assessed
      using the multivariate Cox proportional hazards regression method. RESULTS: The
      median overall survival (OS) time was 29.5 months (range 16.6-42.4 months), the
      1, 3, and 5 year OS were 63%, 40%, and 23%. Cox hazards regression analysis
      revealed that functional remnant liver volume (FRLV), remnant liver volume
      (RLV)/total liver volume (TLV), radiation, tumour number, vascular endothelial
      growth factor (VEGF) distribution, and gross type were the only independent
      predictive factors of outcome (p = 0.039, 0.010, 0.009, 0.034, 0.031, and 0.000,
      respectively). CONCLUSION: TACE combined with RFA was found to be an effective
      therapy, FRLV and RLV/TLV have close correlation with survival for HCC patients
      with PVTT type I, II, or partial III and Child-Pugh A or B.

PMID- 24581963
TI  - Extratemporal abnormalities of brain parenchyma in young adults with temporal
      lobe epilepsy: a diffusion tensor imaging study.
AB  - AIM: To examine extratemporal abnormalities of the cerebral parenchyma in young
      adult temporal lobe epilepsy (TLE) patients using diffusion tensor imaging (DTI).
      MATERIALS AND METHODS: The study comprised 20 adults with unilateral TLE and 20
      controls. The fractional anisotropy (FA), apparent diffusion coefficient (ADC),
      parallel eigenvalue (lambda?), and perpendicular eigenvalue (lambda?) were
      calculated in the regions of interest (ROIs) using a 3 T MRI system. ROIs
      included the anterior/posterior limb of the internal capsule (AIC/PIC), external
      capsule (EC), head of caudate nucleus (HCN), lenticular nucleus (LN), thalamus
      (TL), and genu/body/splenium of the corpus callosum (GCC/BCC/SCC). RESULTS:
      Compared to controls, TLE patients showed lower FA in all ROIs; higher ADC in
      bilateral ECs, HCNs, TLs, and BCC; lower lambda? in the ipsilateral LN and
      bilateral AICs, TL, and GCC; and higher lambda? in all ROIs except the bilateral
      PICs. In TLE patients, the ipsilateral TL had decreased FA compared with the
      contralateral TL. Pearson correlation analysis revealed a negative correlation
      between the ADC of the GCC and the age at onset of epilepsy; the lambda? of the
      ipsilateral PIC and age at onset of epilepsy; the lambda? of the contralateral
      AIC and duration of epilepsy, respectively; and a positive correlation between
      the ADC of the GCC and the duration of epilepsy and the lambda? of the GCC and
      the duration of epilepsy, respectively. CONCLUSION: The study revealed bilateral
      extratemporal abnormalities in young adult TLE patients compared with controls.
      In addition, TLE patients with younger age at onset or longer duration of
      epilepsy may have more serious extratemporal changes.

PMID- 24581964
TI  - The prognostic significance of MRI-detected extramural venous invasion in rectal
      carcinoma.
AB  - AIM: To assess whether there is a significant difference in the incidence of
      patients with metastases of rectal carcinoma at 1 year follow-up between magnetic
      resonance imaging (MRI)-detected extramural venous invasion (EMVI) and those
      without. MATERIALS AND METHODS: A search of our institution's cancer registry
      revealed 788 patients with rectal carcinoma between January 2007 and April 2012.
      Those who were initially staged using MRI and computed tomography (CT)
      chest/abdomen/pelvis, and followed-up with a CT chest/abdomen/pelvis examination
      at 1 year were included in this retrospective study. Patients with synchronous
      metastases were excluded, leaving a cohort of 202 cases. Two consultant
      radiologists reviewed all MRI images and gave a consensus opinion regarding EMVI
      grade and vessel size involved. All CT images were reviewed for metastases.
      Results were analysed using chi-squared and Fisher's exact tests. RESULTS: There
      were 53 cases (26.2%) of EMVI-positive rectal carcinoma. Of the patients with
      EMVI, 24.5% developed metastases at 1 year follow-up, compared to 6.7% of those
      without. There is a significant difference in prognosis between those patients
      with and those without MRI-detected EMVI (chi(2) = 12.29, p < 0.001). Those with
      EMVI have a 3.7 times increased relative risk of developing metachronous
      metastases within 1 year of diagnosis. CONCLUSION: MRI-detected EMVI-positive
      rectal carcinomas are associated with an increased risk of metachronous
      metastases within 1 year of diagnosis. Currently, EMVI status does not directly
      influence the initial management of rectal carcinoma. This available and
      potentially prognostic feature could be used to guide treatment pathways to
      increase disease-free survival.

PMID- 24581965
TI  - Inflammatory myofibroblastic tumours of the liver: gadoxetic acid-enhanced and
      diffusion-weighted MRI findings with 18F-FDG PET/CT and clinical significance of
      regression on follow-up.
AB  - AIM: To assess gadoxetic acid-enhanced and diffusion-weighted (DW) magnetic
      resonance imaging (MRI) findings of inflammatory myofibroblastic tumours (IMTs)
      of the liver using combined 2-[(18)F]-fluoro-2-deoxy-D-glucose (FDG) positron
      emission tomography (PET)/computed tomography (CT), and to evaluate clinical
      course with volume change on follow-up. MATERIALS AND METHODS: Gadoxetic acid
      enhanced and DW MRI findings of 18 histopathologically proven hepatic IMTs in 13
      patients were retrospectively reviewed. The clinical features, qualitative
      (signal intensity and enhancement pattern) and quantitative data [apparent
      diffusion coefficient (ADC)], and analysis of FDG-PET/CT findings were collected.
      The volume of IMTs during follow-up was measured using a tumour half-time.
      RESULTS: Most of the IMTs (9/13, 69.2%) were found incidentally. IMTs were
      predominantly seen as well-defined (16/18, 88.9%) masses with peritumoural
      hypointensity during the hepatobiliary phase (17/18, 94.4%) and showed five
      morphological types: target-like hypervascular mass (n = 9), hypovascular mass (n
      = 5), heterogeneous enhancing mass (n = 2), sclerosing mass (n = 1), and non
      target hypervascular mass (n = 1). All lesions showed diffusion restriction and
      hypermetabolic mass on FDG-PET/CT images. The mean ADC value and ADC ratio of
      IMTs to liver were 0.828 * 10(-3) mm(2)/s and 0.76, respectively. On follow-up,
      all 11 IMTs showed rapid regression (mean tumour half-time, 38.49 days) with no
      tumour recurrence or distant metastasis. CONCLUSION: Although hepatic IMTs can
      mimic abscess and malignant tumours at MRI and PET/CT, peritumoural hypointensity
      during the hepatobiliary phase with rapid regression on follow-up could be
      helpful for differentiating it from other lesions.

PMID- 24581966
TI  - Non-neoplastic hepatic vascular diseases: spectrum of CT and MRI appearances.
AB  - The unique dual blood supply of the liver makes it one of the common sites for
      various vascular neoplastic and non-neoplastic diseases. Increasing use of
      multiphase contrast-enhanced computed tomography (CT) and dynamic magnetic
      resonance imaging (MRI) has led to increased identification of numerous non
      neoplastic vascular entities apart from already well-known neoplastic lesions.
      The objective of this review is to describe the causes and clinical features and
      to familiarize the reader with the key imaging features of various non-neoplastic
      vascular diseases affecting the liver. Non-neoplastic vascular diseases are
      classified broadly as those affecting the hepatic veins, portal veins, hepatic
      artery, intrahepatic shunts, and other miscellaneous conditions. 

PMID- 24581957
TI  - Diagnostic approach to the congenital muscular dystrophies.
AB  - Congenital muscular dystrophies (CMDs) are early onset disorders of muscle with
      histological features suggesting a dystrophic process. The congenital muscular
      dystrophies as a group encompass great clinical and genetic heterogeneity so that
      achieving an accurate genetic diagnosis has become increasingly challenging, even
      in the age of next generation sequencing. In this document we review the
      diagnostic features, differential diagnostic considerations and available
      diagnostic tools for the various CMD subtypes and provide a systematic guide to
      the use of these resources for achieving an accurate molecular diagnosis. An
      International Committee on the Standard of Care for Congenital Muscular
      Dystrophies composed of experts on various aspects relevant to the CMDs performed
      a review of the available literature as well as of the unpublished expertise
      represented by the members of the committee and their contacts. This process was
      refined by two rounds of online surveys and followed by a three-day meeting at
      which the conclusions were presented and further refined. The combined consensus
      summarized in this document allows the physician to recognize the presence of a
      CMD in a child with weakness based on history, clinical examination, muscle
      biopsy results, and imaging. It will be helpful in suspecting a specific CMD
      subtype in order to prioritize testing to arrive at a final genetic diagnosis. 

PMID- 24581967
TI  - Relative ADC measurement for liver fibrosis diagnosis in chronic hepatitis B
      using spleen/renal cortex as the reference organs at 3 T.
AB  - AIM: To evaluate whether the relative apparent diffusion coefficient (rADC) can
      help determine the stage of liver fibrosis in patients with chronic hepatitis B
      virus (HBV) by using the spleen and renal cortex as reference organs. MATERIALS
      AND METHODS: Sixty-seven chronic HBV patients and nine patients with focal
      hepatic lesions, but normal hepatic function, underwent 3 T magnetic resonance
      imaging (MRI) using diffusion-weighted imaging (DWI) with b values of 0, 200,
      600, and 800 s/mm(2). Liver ADC and rADC (S-rADC and R-rADC, defined as the ratio
      of liver ADC to spleen and renal cortex ADC, respectively) were measured and
      compared by using METAVIR liver fibrosis scores. All statistical analyses were
      performed using Spearman's correlation test, the Kruskal-Wallis test, and a
      receiver operating characteristic (ROC) analysis with area under the curve (AUC).
      RESULTS: The mean liver ADC and the two rADC decreased with rising fibrosis
      scores at all b values (p < 0.05 for all comparisons). The R-rADC at b = 600
      s/mm(2) was most strongly correlated to the fibrosis scores (r = -0.697; p <
      0.001), and was among the best predictors in estimating fibrosis stages >= F2
      (AUC = 0.885 versus 0.701-0.866), >= F3 (0.806 versus 0.617-0.808), and =F4
      (0.884 versus 0.683-0.835). The ability of S-rADC to predict stage >= F2/>= F3
      and =F4 showed no advantage to the liver ADC value at b = 600 and 800 s/mm(2)
      (AUC comparisons: all p > 0.05). CONCLUSION: Renal-cortex-referenced ADC
      measurement at 3 T DWI using a median b-value of 600 s/mm(2) might be more
      accurate to predict hepatic fibrosis than referencing the spleen.

PMID- 24581968
TI  - Diffusion-weighted imaging in urinary tract lesions.
AB  - Diffusion-weighted imaging (DWI) utilizes the signal contrast provided by the
      regional differences in the Brownian motion of water molecules, which is a direct
      reflection of the cellular micro-environment. DWI emerged as a revolutionary
      magnetic resonance imaging (MRI) technique in the field of stroke imaging. As far
      as body imaging is concerned, DWI has come a long way from being an experimental
      technique to an essential element of almost all abdominal MRI examinations. This
      progress has been made possible by technical advancements in MRI systems, as well
      as a better understanding of MRI physics. DWI is quick to perform and has the
      potential to provide crucial information about the disease process without adding
      much to the total imaging time. This article provides a brief review of the basic
      principles of DWI with insights to the information that DWI provides in the
      evaluation of various diseases of the urinary tract at both 1.5 and 3 T. DWI is
      helpful for differentiation of various histopathological subtypes of renal cell
      carcinoma (RCC). Prediction of histopathological grade of RCC is also becoming
      possible solely based on DWI. Assessment of response to chemotherapeutic agents
      is possible based on the change in the ADC (apparent diffusion coefficient)
      value. DWI performed with high b-values increases the confidence in diagnosing
      prostatic carcinoma. This article highlights the emerging role of DWI in the
      evaluation of urinary tract lesions.

PMID- 24581970
TI  - Imaging of thymus in myasthenia gravis: from thymic hyperplasia to thymic tumor.
AB  - Myasthenia gravis (MG) is an autoimmune disorder often associated with thymic
      abnormalities. At onset, thymic lymphoid hyperplasia (TLH) and thymoma can be
      found in up to 65% and 15% of patients, respectively. Diagnostic imaging is
      crucial in this setting in order to detect the presence and type of the thymic
      abnormality and in the preoperative planning, when indicated. Chest radiography
      has a minor role due to its low accuracy. Computed tomography is the imaging
      modality of choice, although the differentiation between a small thymoma and TLH
      that appears as a focal soft-tissue mass may be not possible. Magnetic resonance
      imaging (MRI) is not usually employed, but it is useful in equivocal cases,
      especially in differentiating focal TLH from thymoma by using chemical-shift
      sequences for defining the proper management. In addition, diffusion-weighted
      (DW)-MRI can differentiate lipid-poor normal/hyperplastic thymus from thymoma and
      could be useful in differentiating non-advanced from advanced thymomas. Positron
      emission tomography (PET)-CT is not helpful in distinguishing early from advanced
      thymoma but can be used to differentiate thymic carcinoma from thymoma. Hereby,
      we discuss the imaging features of thymic abnormalities in MG, even focusing on
      novel aspects of chemical-shift and DW-MRI. 

PMID- 24581969
TI  - Diagnostic accuracy of 18F-FDG PET/CT for detection of advanced colorectal
      adenoma.
AB  - AIM: To determine the accuracy of 2-[(18)F]-fluoro-2-deoxy-d-glucose (FDG)
      positron-emission tomography (PET) in the detection of advanced colorectal
      adenomas. MATERIALS AND METHODS: In this retrospective study, patient consent was
      waived by the institutional review board. Combined FDG whole-body PET and
      computed tomography (CT) images (2000-2009) were re-read and compared with
      reports of complete colonoscopy performed up to 1 year after the PET examination.
      One or more areas of focal colonic uptake greater than the background indicated a
      positive PET result, irrespective of standardized uptake value (SUV). Lesion and
      patient-level measures of PET accuracy with their 95% confidence intervals (CI)
      were calculated. RESULTS: One hundred and eighty patients undergoing colonoscopy
      with or without biopsy underwent PET within 1 year prior to colonoscopy. There
      were 92 women and 88 men (mean age 63.3 years). Indications for PET were extent
      of disease and treatment response in all cases. Patients had non-colorectal
      cancer (n = 160) or colon cancer (n = 20). One hundred and fourteen FDG-avid
      lesions were present. In 33, there was no colonoscopic correlate. Two hundred and
      fifty-eight biopsies revealed tubular adenomas (n = 91, one with intra-mucosal
      cancer), tubulovillous adenomas (n = 28), adenocarcinoma (n = 37), inflammation
      (n = 22), hyperplastic polyps (n = 54), serrated adenoma (n = 5), metastatic
      disease (n = 5), normal/benign mucosa or submucosal benign tumors (n = 13) or
      miscellaneous (n = 3). Per-lesion performance of PET showed a sensitivity of 38%
      (95% CI: 31-46; 64/167) for all adenomas and carcinomas and 58% (95% CI: 49-67;
      57/98) for lesions >= 10 mm. At the patient level, for all adenomas and
      carcinomas the sensitivity was 54% (95% CI: 44-63; 61/113), specificity 100% (pre
      defined), positive predictive value (PPV) 100% (pre-defined), and negative
      predictive value (NPV) 56% (95% CI: 47-65; 67/119). For patients with advanced
      adenoma, PET sensitivity was 49% (95% CI: 35-63; 26/53) specificity, 100%, PPV
      100% and NPV 82% (95% CI: 76-88; 127/154). Five of 37 adenocarcinomas were not
      detected, one of which was mucinous at histology. CONCLUSION: FDG PET detected
      most cancers, but only identified one-half of patients harbouring advanced
      adenomas. Based on the data, PET cannot be relied upon to accurately identify
      patients with advanced adenoma.

PMID- 24581971
TI  - 2D and 3D MRI features of classic bladder exstrophy.
AB  - The bladder exstrophy-epispadias complex (EEC) represents a spectrum of rare and
      surgically correctable congenital anomalies. Classic bladder exstrophy (CBE)
      stands between epispadias and cloacal exstrophy (CE) in the severity spectrum,
      and is the most commonly encountered type. CBE involves congenital defects of the
      bladder, abdominal wall, pelvic floor, and bony pelvis. With the growing
      understanding of the detrimental effects of radiation in children, magnetic
      resonance imaging (MRI) is progressively been utilized in the preoperative work
      up and post-surgical follow-up of these patients. MRI provides valuable
      information for planning and evaluating the optimal surgical techniques for
      closure of CBE. The aim of this paper is to provide a review of the two- (2D) and
      three-dimensional (3D) MRI features of CBE including a detailed analytical
      description of the anatomy of the pelvic floor in affected patients. 

PMID- 24581972
TI  - Preference for human eyes in human infants.
AB  - Despite evidence supporting an early attraction to human faces, the nature of the
      face representation in neonates and its development during the first year after
      birth remain poorly understood. One suggestion is that an early preference for
      human faces reflects an attraction toward human eyes because human eyes are
      distinctive compared with other animals. In accord with this proposal, prior
      empirical studies have demonstrated the importance of the eye region in face
      processing in adults and infants. However, an attraction for the human eye has
      never been shown directly in infants. The current study aimed to investigate
      whether an attraction for human eyes would be present in newborns and older
      infants. With the use of a preferential looking time paradigm, newborns and 3-, 6
      , 9-, and 12-month-olds were simultaneously presented with a pair of nonhuman
      primate faces (chimpanzees and Barbary macaques) that differed only by the eyes,
      thereby pairing a face with original nonhuman primate eyes with the same face in
      which the eyes were replaced by human eyes. Our results revealed that no
      preference was observed in newborns, but a preference for nonhuman primate faces
      with human eyes emerged from 3months of age and remained stable thereafter. The
      findings are discussed in terms of how a preference for human eyes may emerge
      during the first few months after birth. 

PMID- 24581973
TI  - Long-term biocompatibility and visual outcomes of a hydrophilic acrylic
      intraocular lens in patients with uveitis.
AB  - PURPOSE: To report the long-term visual outcomes and biocompatibility of a single
      piece hydrophilic acrylic intraocular lens (IOL) in patients with uveitis having
      cataract surgery. SETTING: Tertiary referral center, Birmingham, United Kingdom.
      DESIGN: Retrospective case review. METHODS: The review included consecutive
      uveitis patients in whom phacoemulsification and acrylic IOL implantation was
      performed by the same surgeon. Outcomes measures are reported as rate/eye-year
      and included visual acuity and signs of bioincompatibility. RESULTS: The review
      identified 171 eyes (140 patients; mean age 51 years [range 16 to 85 years]) with
      uveitis. The mean follow-up was 3.8 years (range 0.9 to 10.3 years). Signs of
      uveal bioincompatibility were found in 31 eyes, with visually insignificant
      deposits on the IOL in 17 eyes. The rate of uveal bioincompatibility was 0.06/eye
      year. Signs of capsule bioincompatibility were found in 107 (63%) of 171 eyes
      (0.31/eye-year). Posterior capsule opacification was documented in 102 eyes
      (0.29/eye-year); neodymium:YAG laser capsulotomy was required in 31 eyes
      (0.05/eye-year). The rate of failure to maintain a 3 logMAR line improvement in
      corrected distance visual acuity (CDVA) was 0.08/eye-year; to maintain better
      than 0.3 logMAR, 0.15/eye-year; and to maintain either, 0.04/eye-year. At 1 year,
      85% of eyes had a CDVA of better than 0.3 logMAR or maintained a 3 logMAR-line
      improvement. Eyes with preexisting macular or optic nerve disease had
      significantly worse visual outcomes. CONCLUSIONS: The long-term safety profile of
      the hydrophilic acrylic IOL was good in uveitis cases, leading to good visual
      outcomes and a low rate of vision-impairing uveal and capsule complications.
      FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any
      material or method mentioned.

PMID- 24581974
TI  - Cataract surgical skill assessment tools.
AB  - After publication of the Accreditation Council for Graduate Medical Education's
      required competencies for residency training programs, ophthalmology training
      programs began developing objective assessments to measure resident surgical
      skill. The application of these evaluation tools represents a move toward
      standardization in the resident educational process. This review of the
      assessment tools found that the evaluation rubrics for cataract surgery vary in
      their level of reliability and validity. Currently, variations in reliability and
      validity are the only measure of true differences in the evaluation rubrics.
      Future studies will determine which of the assessment tools is the most practical
      and efficient for resident training. FINANCIAL DISCLOSURE: Neither author has a
      financial or proprietary interest in any material or method mentioned.

PMID- 24581975
TI  - Ophthalmic viscosurgical device-assisted sutureless-incision cataract surgery for
      a hard nucleus or mature cataract.
AB  - We describe a modified method of sutureless-incision cataract surgery using an
      ophthalmic viscosurgical device (OVD) to extract a hard lenticular nucleus or
      mature cataract. After an isosceles trapezoid-shaped sclerocorneal tunnel and a
      round 7.0 mm diameter capsulorhexis are made, the nucleus is displaced into the
      anterior chamber. As OVD is injected, the OVD cannula acts as a slide to guide
      the nucleus out of the eye. Ophthalmic viscosurgical device-assisted sutureless
      incision cataract surgery was used in a consecutive series of 182 eyes with a
      hard nucleus (57 eyes), mature cataract (47 eyes), or both (78 eyes). No
      posterior capsule rupture or vitreous loss occurred during surgery and no wound
      leakage or hypotony occurred postoperatively. The uncorrected visual acuity
      improved to 20/60 or better in 122 eyes (67%) on the first postoperative day.
      Ophthalmic viscosurgical device-assisted sutureless-incision cataract surgery,
      usually without additional instruments or sutures, offers an effective and
      uncomplicated technique for managing a brunescent or mature cataract. FINANCIAL
      DISCLOSURE: No author has a financial or proprietary interest in any material or
      method mentioned.

PMID- 24581978
TI  - The benefits of chocolate.

PMID- 24581976
TI  - Variability of hemoglobin F expression in hemoglobin EE disease: hematological
      and molecular analysis.
AB  - Although the molecular basis of variability of hemoglobin (Hb) F has been
      extensively examined in beta-thalassemia and sickle cell diseases, less study has
      been done on Hb E disorder. To address the variability of Hb F expression in Hb
      EE disease, we have examined multiple single nucleotide polymorphisms (SNPs) in
      the beta-globin gene cluster, BCL11A and HBS1L-MYB genes and determined their
      associations with Hb F levels in this syndrome. Study was done on 141 adult Thai
      individuals with homozygous Hb E. Hematological parameters were recorded and Hb F
      measured using Hb-HPLC analyzer. It was found in 26 cases that co-inheritance of
      alpha-thalassemia could lead to significant lower production of Hb F. Association
      of Hb F expression with the (G)gamma-Xmn I polymorphism and other SNPs including
      rs2297339, rs2838513, rs4895441 and rs9399137 in HBS1L-MYB gene and rs4671393 and
      rs11886868 in BCL11A gene was therefore analyzed in the remaining 115 cases
      without alpha-thalassemia. It was found that 4 of these 7 SNPs including (G)gamma
      XmnI polymorphism (rs7482144), HBS1L-MYB (rs4895441) and (rs9399137) and BCL11A
      (rs4671393) were significantly associated with higher proportions of subjects
      with high Hb F (Hb F>=5%). The result demonstrated that multiple genetic
      modifying factors including T allele of (G)gamma-XmnI polymorphism (rs7482144), G
      allele of HBS1L-MYB (rs489441), C allele of HBS1L-MYB (rs9399137) and C allele of
      BCL11A (rs4671393) are associated with increased Hb F and in combination could
      explain approximately 80% of the variation of Hb F in Hb EE disease in Thai
      population. Other genetic factors regulating Hb F expression in this common
      genetic disorder remains to be elucidated.

PMID- 24581979
TI  - Toward global prevention of sexually transmitted infections (STIs): the need for
      STI vaccines.
AB  - An estimated 499 million curable sexually transmitted infections (STIs;
      gonorrhea, chlamydia, syphilis, and trichomoniasis) occurred globally in 2008. In
      addition, well over 500 million people are estimated to have a viral STI such as
      herpes simplex virus type 2 (HSV-2) or human papillomavirus (HPV) at any point in
      time. STIs result in a large global burden of sexual, reproductive, and maternal
      child health consequences, including genital symptoms, pregnancy complications,
      cancer, infertility, and enhanced HIV transmission, as well as important
      psychosocial consequences and financial costs. STI control strategies based
      primarily on behavioral primary prevention and STI case management have had clear
      successes, but gains have not been universal. Current STI control is hampered or
      threatened by several behavioral, biological, and implementation challenges,
      including a large proportion of asymptomatic infections, lack of feasible
      diagnostic tests globally, antimicrobial resistance, repeat infections, and
      barriers to intervention access, availability, and scale-up. Vaccines against HPV
      and hepatitis B virus offer a new paradigm for STI control. Challenges to
      existing STI prevention efforts provide important reasons for working toward
      additional STI vaccines. We summarize the global epidemiology of STIs and STI
      associated complications, examine challenges to existing STI prevention efforts,
      and discuss the need for new STI vaccines for future prevention efforts. 

PMID- 24581980
TI  - Blastocyst culture selects for euploid embryos: comparison of blastomere and
      trophectoderm biopsies.
AB  - Preimplantation genetic diagnosis and screening improves the chances of achieving
      a viable pregnancy, not only free of undesired single-gene defects but also
      aneuploidy. In addition, improvements in vitrification provide an efficient means
      of preserving embryos (blastocysts). By combining trophectoderm biopsy with
      recent improvements in vitrification methods, only those embryos that have proved
      themselves viable and potentially more competent are tested. Using array
      comparative genomic hybridization (aCGH) to assess all 24 chromosomes, aneuploidy
      rates were compared between day-3 blastomere biopsy and day-5 trophectoderm
      biopsy. Of those 1603 embryos, 31% were euploid, 62% were aneuploid and 7% not
      analysable. A significantly larger proportion of embryos were euploid on day-5
      biopsy (42%) compared with day-3 biopsy (24%, P<0.0001). The number of euploid
      embryos per patient was not significantly different. Combining extended culture,
      trophectoderm biopsy and aneuploidy assessment by aCGH and subsequent
      vitrification can provide a more efficient means of achieving euploid pregnancies
      in IVF.

PMID- 24581981
TI  - Spermatozoa as a transport system of large unilamellar lipid vesicles into the
      oocyte.
AB  - In addition to their role as man-made membranes, vesicles continue to be
      investigated as carriers for drug delivery. While most research focuses on their
      injectable properties, here a new delivery strategy is proposed. It is shown that
      spermatozoa can transport vesicles of variable composition. For human
      spermatozoa, the vesicles started to show binding after 20 mol% of the nonbinding
      vesicle backbone lipids were substituted with positive, negative, cerebroside or
      ganglioside lipids. Vesicle binding is a dynamic process with constant 'on' and
      'off' binding. The physiological and motility attributes of the spermatozoa are
      not affected by the attached vesicles. Sperm swimming characteristics changed
      only marginally. Also, the activation status of the acrosomal membrane, tested
      with the fluorescent probe Pisum sativum agglutinin, was not affected by vesicle
      binding. Moreover, the hyaluronic acid-binding test showed that viable, fully
      developed spermatozoa will attach and remain bound to hyaluronic acid-coated
      slides regardless of vesicle binding. Therefore a new 'hybrid' delivery system
      was created with human spermatozoa, and tested with a mouse IVF system. Large
      unilamellar vesicles physisorbed to mouse spermatozoa can not only penetrate the
      mouse oocytes in these proof-of-principle experiments, but also deliver the cargo
      placed within the vesicles.

PMID- 24581982
TI  - The human first cell cycle: impact on implantation.
AB  - The morphology of fertilization events has been related to successful
      implantation by subjective criteria (pronuclei score, pronuclei symmetry and
      position). This work first described these events by time-lapse technology and
      then compared the timings of fertilization events (second polar body extrusion,
      first and second pronuclei appearance, abuttal and fading) in implanted versus
      nonimplanted embryos in a 2-year cohort retrospective study. A total of 1448
      transferred embryos from 842 patients undergoing intracytoplasmic sperm injection
      with oocyte donation were monitored, 212 embryos from treatments where the number
      of gestational sacs matched the number of transferred embryos and 687 embryos
      from treatments no biochemical pregnancy was achieved. The timings at which
      second polar body extrusion (3.3-10.6 h), pronuclear fading (22.2-25.9 h) and
      length of S-phase (5.7-13.8 h) occurred were linked successfully to embryo
      implantation. The other parameters were apparently not related, as determined by
      image acquisition and time-lapse analysis.

PMID- 24581983
TI  - Impact of PCOS on early embryo cleavage kinetics.
AB  - This study investigated whether polycystic ovary syndrome (PCOS) affected early
      embryo development assessed by time-lapse analysis of embryo kinetics from
      fertilization to the blastocyst stage. This was a prospective cohort study of two
      pronuclei (2PN) embryos from 25 hyperandrogenic PCOS patients (110 2PN embryos),
      26 normoandrogenic PCOS patients (140 2PN embryos) and 20 healthy, regularly
      cycling women (controls, 97 2PN embryos). Patients underwent the same baseline
      evaluation and the same ovarian stimulation from April 2010 to February 2013.
      Oocytes were fertilized by intracytoplasmic sperm injection and incubated in an
      EmbryoScope with pictures taken every 20 min in seven focal planes. Time to 2PN
      breakdown, first cleavage and cleavage to 3, 4, 5, 6, 7 and 8 cells, morula and
      blastocyst (t2, t3, t4, t5, t6, t7, t8, t(M), t(B)) were annotated. Differences
      in embryo kinetics between groups were assessed by mixed modelling. Compared with
      controls, embryos from hyperandrogenic PCOS patients were significantly delayed
      at 2PN breakdown, t2, t3, t4 and t7 but not at t5, t6, t8, t(M) or t(B). Embryos
      from hyperandrogenic PCOS women had developed slower from fertilization to the 8
      cell stage compared with embryos from controls.

PMID- 24581984
TI  - Live birth rates in Bologna poor responders treated with ovarian stimulation for
      IVF/ICSI.
AB  - This retrospective study determined the efficacy of ovarian stimulation for
      IVF/intracytoplasmic sperm injection (ICSI) in poor ovarian responders fulfilling
      the Bologna criteria for poor ovarian response and identified predictors of live
      birth rates. Overall, 485 patients undergoing 823 ovarian stimulation cycles for
      IVF/ICSI with maximum gonadotrophin dose (>= 300 IU) between January 2009 and
      December 2011 were included. Patients were considered eligible, irrespective of
      the treatment protocol, if they were classified as poor responders based on the
      recently developed definition for poor ovarian response by the European Society
      of Human Reproduction and Embryology, the Bologna criteria. Live birth rates did
      not significantly differ between women aged <40 and women aged >= 40 years either
      per cycle (7.1 versus 5.2%, OR 1.38, 95% CI 0.77-2.46) or per patient (11.6
      versus 8.8%, OR 1.36, 95% CI 0.75-2.46). In logistic regression analysis, the
      number of oocytes retrieved was the only variable significantly associated with
      live births (OR 1.92, 95% CI 1.03-3.55 for >3 versus 1-3 oocytes). Bologna poor
      responders demonstrate very low live birth rates, irrespective of age and
      treatment protocol used. An increase in the number of oocytes retrieved is an
      independent variable related to live birth rates.

PMID- 24581985
TI  - The development of endometriosis in a murine model is dependent on the presence
      of dendritic cells.
AB  - Endometriosis is a common condition associated with pelvic pain and infertility.
      This study group has previously shown that supplementation of dendritic cells led
      to enhancement of endometriosis lesion growth and angiogenesis. This study
      determined whether endometriosis is dependent on the presence of endogenous
      dendritic cells. Surgical induction of endometriosis was performed in CD11c+
      DTR/GFP transgenic (Tg) female mice in which dendritic cells were ablated upon
      injection of diphtheria toxin (DT). Mice were allocated into four groups (n=5
      each): group I, wild-type mice treated with vehicle; group II, wild-type mice
      treated with DT; group III, Tg mice treated with DT; and group IV, Tg mice
      treated with vehicle. After 10 days, mice were killed and endometriosis lesions
      were analysed by flow cytometry. DT treatment led to ablation of dendritic cells
      in spleens and endometriosis lesions in Tg mice while no ablation was observed in
      controls. Corresponding to dendritic cell ablation, endometriosis lesions in
      group III were ~5-fold smaller than in the control groups (ANOVA P<0.0001). This
      study suggests that endometriosis development is dependent on the presence of
      endogenous dendritic cells. Therapies designed to inhibit dendritic cell
      infiltration as possible treatments for endometriosis warrant further study.

PMID- 24581986
TI  - What exactly do we mean by 'recurrent implantation failure'? A systematic review
      and opinion.
AB  - Recurrent implantation failure (RIF) is an iatrogenic condition, being the result
      of repetitive unsuccessful cycles of IVF or intracytoplasmic sperm injection
      (ICSI) treatment. The aim of this review was to assess the definitions of RIF
      used in literature as well as suggest a uniform definition of this condition. A
      systematic search of MEDLINE, Embase and Cochrane Library was conducted. The most
      commonly stated definitions described RIF as 'three or more failed treatment
      cycles' or 'two or more failed cycles'. Other identified definitions were based
      solely on the number of embryos transferred in previous cycles or combined the
      number of previously failed cycles with the number of transferred embryos.
      Several other definitions were also identified. This review highlights the lack
      of uniformity of the definition of RIF. Based on the available literature and the
      expert opinion of the authors, RIF should be defined as the absence of
      implantation after two consecutive cycles of IVF, ICSI or frozen embryo
      replacement cycles where the cumulative number of transferred embryos was no less
      than four for cleavage-stage embryos and no less than two for blastocysts, with
      all embryos being of good quality and of appropriate developmental stage.

PMID- 24581987
TI  - Telomere length in human blastocysts.
AB  - This is a retrospective study aiming to assess telomere length in human embryos 4
      days post fertilization and to determine whether it is correlated to chromosomal
      ploidy, embryo developmental rate and patient age. Embryos were donated from
      patients undergoing treatment in the assisted conception unit. Seven couples took
      part, generating 35 embryos consisting of 1130 cells. Quantitative fluorescent in
      situ hybridization (FISH) measured the telomere length of every cell using a pan
      telomeric probe. Conventional FISH on six chromosomes was used to assess
      aneuploidy in the same cells. Maternal and paternal age, referral reason, embryo
      developmental rate and type of chromosomal error were taken into account.
      Chromosomally abnormal cells were associated with shorter telomeres than normal
      cells for embryos that were developmentally slow. Cells produced by women of
      advanced maternal age and those with a history of repeated miscarriage tended to
      have substantially shorter telomeres. There was no significant difference in
      telomere length with respect to the rate of embryo development 5 days post
      fertilization. Telomeres play an important role in cell division and shorter
      telomeres may affect embryonic ploidy. Reduced telomere length was associated
      with aneuploid cells and embryos from women of advanced maternal age.

PMID- 24581988
TI  - Is it acceptable to destroy or include human embryos before day 5 in research
      programmes?
AB  - Day-3 poor-quality embryos (PQE) from IVF-embryo transfer cycles are usually
      destroyed or are included in research programmes. Knowing that these embryos have
      the ability to evolve to the blastocyst stage and yield embryonic stem cell
      lines, this study postulated that they could also give rise to live births. This
      is a prospective study including 186 IVF-embryo transfer candidates who had
      obtained at least one supernumerary PQE on day 3. PQE were kept for extended
      culture and high-quality blastocysts were frozen. A total of 620 PQE were
      eligible for the study, 217 (35.0%) reached the blastocyst stage and 73 (33.6%)
      were frozen. Blastulation rates were 7-fold higher (OR 7.29, 95% CI 5.01-10.61)
      in embryos compacted on day 4. Of the frozen blastocysts, 40 were thawed during
      33 thawed blastocyst transfer cycles, which led to 10 clinical pregnancies. These
      pregnancies resulted in five miscarriages and five healthy live births at full
      term. PQE may achieve their development to the blastocyst stage, be frozen-thawed
      and harbour reasonable implantation potential. These results, thereby, raise an
      ethical issue regarding the fate reserved to PQE.

PMID- 24581989
TI  - Short follicular phase of stimulation following corifollitropin alfa or daily
      recombinant FSH treatment does not compromise clinical outcome: a retrospective
      analysis of the Engage trial.
AB  - To evaluate whether a short follicular phase of ovarian stimulation compromises
      the chance of pregnancy, subjects from a double-blind, randomized trial treated
      with a single dose of corifollitropin alfa (n=756) or daily recombinant FSH
      (n=750) were categorized as early responders if three follicles >=17 mm were
      reached and human chorionic gonadotrophin (HCG) was administered prior to or on
      stimulation day 8, and as normal responders if three follicles >=17 mm were
      reached and HCG was administered after stimulation day 8. In the corifollitropin
      alfa and recombinant FSH groups, 23.2% and 29.1%, respectively, were early
      responders (P=0.01). Regardless of the treatment group, the initial ovarian
      response was higher in early responders, but with two extra days of stimulation,
      the number and size of follicles on the day of HCG in the normal responders was
      similar to those of the early responders. The number of oocytes was similar in
      both response groups following corifollitropin alfa treatment (13.6 versus 14.5)
      and recombinant FSH treatment (12.8, both groups). The ongoing pregnancy rates
      were comparable for early and normal responders regardless of the treatment
      group, supporting successful outcome following a stimulation period of only 1
      week.

PMID- 24581990
TI  - Influence of temperature and sperm preparation on the quality of spermatozoa.
AB  - This study investigated the effects of long-term (24h) in-vitro sperm incubation
      at room temperature (RT; 23 degrees C) versus testis temperature (35 degrees C)
      on various sperm-quality parameters. Semen samples (n=41) were prepared both by
      density-gradient centrifugation (DGC) and the swim-up technique in order to
      compare the influence of sperm preparation on sperm quality after incubation.
      Progressive motility and morphology were significantly higher after incubation at
      RT compared with 35 degrees C (P<0.001 and P<0.01, respectively). The proportions
      of acrosome-reacted, apoptotic and dead spermatozoa were significantly lower in
      samples incubated for 24h at RT compared with 35 degrees C (P<0.001, P=0.01 and
      P<0.001, respectively). The number of motile, morphologically normal, non
      acrosome-reacted and nonapoptotic spermatozoa recovered after sperm preparation
      was significantly higher in DGC compared with swim-up samples (P<0.001). However,
      spermatozoa prepared by swim-up showed better survival after incubation compared
      with DGC-prepared spermatozoa, especially when incubated at 35 degrees C. In
      conclusion, this study indicates a significantly better and longer preservation
      of sperm quality when incubation is performed at RT. These findings may convince
      laboratories to change the routinely used sperm storage conditions in order to
      maximize the quality of the prepared sperm sample.

PMID- 24581991
TI  - Characterizing the practice of oocyte donation: a web-based international survey.
AB  - Although oocyte donation is widely practised, few interventions in this field are
      evidence based. The objective of this study was to describe the current practices
      for evaluation and treatment of oocyte donors and recipients worldwide. Through
      an IVF-focused website, an internet-based survey was addressed to physicians in
      IVF units worldwide. A total of 161 units responded, reflecting 14,890 annual
      oocyte donation cycles. The majority (83.3%) of centres perform genetic testing
      for oocyte donors, and in 94.6% of cycles, donors are <35 years old. Anonymous
      donors are most commonly used (91.3%) and 95.8% are fresh donations. In 51.4% of
      donor cycles, the gonadotrophin-releasing hormone (GnRH) antagonist protocol is
      used, and in 29.8% of these cycles, a GnRH agonist is prescribed for the
      ovulatory trigger. Recipient pituitary suppression is used in 76.7% of cycles,
      and oral oestrogen (86.4%) and vaginal progesterone (73.8%) are the preferred
      routes of administration for endometrial preparation. In the majority (51.5%) of
      cycles, a minimum endometrial thickness of >= 7 mm is required. This study
      reflects a relative lack of homogeneity in management of oocyte donors and
      recipients and highlights the need for developing a consensus in the practice of
      oocyte donation based upon evidence-based medicine.

PMID- 24581992
TI  - Transfer of blastocysts with deviant morphological and morphokinetic parameters
      at early stages of in-vitro development: a case series.
AB  - Time-lapse imaging is increasingly applied as an adjunct to reproductive
      medicine. The gained information of the morphological and morphokinetic variables
      before the onset of transcription are supposed to be good predictors for the
      selection of the best embryo for transfer and are often seen in line with
      clinical outcomes. This retrospective case series investigated the outcome of
      transferred blastocysts that did not fulfil the proposed embryo scores at early
      cleavage or at later stages of development. The observations were made by time
      lapse imaging. This study reports the birth of 16 healthy children after day-5
      blastocyst transfer, of which at least one of the transferred embryos originated
      from deviant morphology and/or kinetic cleavage patterns. This case series
      suggests that some blastocysts derived from embryos with poor conventional
      morphological score and/or suboptimal morphokinetics can be successfully
      transferred and might result in live births. Such results might raise awareness
      that discarding embryos based only on early events is not a suitable approach to
      give patients the chance to conceive. In conclusion, to date only the transfer of
      viable embryos after culturing them until day 5 guarantees optimal embryo
      selection and helps to prevent embryo wastage.

PMID- 24581993
TI  - Validation of open inguinal hernia repair simulation model: a randomized
      controlled educational trial.
AB  - BACKGROUND: A hernia repair open surgical simulation computer software was
      developed at Imperial College London. A randomized controlled educational trial
      was conducted to investigate the benefit of the simulation on the development of
      procedural knowledge. METHODS: Medical students in their clinical years were
      invited to participate in the trial. Students were block randomized to 4 groups:
      G1--Interactive Simulation; G2--Non-interactive Simulation; G3--Video Tutorial;
      G4--Control. On completion, they were objectively assessed on their ability to
      recall the tasks involved in an open inguinal hernia repair in the form of a
      multiple choice question (MCQ) and a simulated discussion with a consultant
      surgeon. RESULTS: Fifty-six students completed the study. Each arm carries
      similar baseline scores (pre-intervention MCQ) with means 43.33, 38.92, 38.33,
      and 39.57 in G1 to G4, respectively. MCQ score improvements and final assessment
      scores proved better in the intervention groups (1, 2, and 3) compared to
      controls. CONCLUSION: The interactive simulation has shown an objective benefit
      in teaching medical students the anatomical and procedural knowledge in
      performing an open inguinal hernia repair.

PMID- 24581994
TI  - Therapeutic nipple-sparing mastectomy: trends based on a national cancer
      database.
AB  - BACKGROUND: Current reports on nipple-sparing mastectomy (NSM) are limited to
      single-institution series. We use the National Cancer Institute's Surveillance,
      Epidemiology, and End Results database to report on the national experience with
      NSM. METHODS: Population-level deidentified data were extracted from the
      Surveillance, Epidemiology, and End Results database. All female breast cancer
      patients treated with NSM from 2005 to 2009 were included. Case analysis was
      performed with respect to demographic and oncologic characteristics. RESULTS:
      Four hundred forty-nine patients underwent therapeutic NSM; this number increased
      from 66 patients in 2005 to 133 in 2009. Patients were distributed across 16
      regions, although nearly 50% were from a region of California. Tumor diameter was
      <2 cm in 224 patients (50%). Lymph nodes were positive in 59 patients (13%),
      while radiation was delivered to 74 patients (16%). CONCLUSIONS: NSM use has been
      increasing over the past several years. A majority of patients have tumor size <2
      cm, although the number of patients with tumor size >=2 cm has increased over
      time. Further population-based studies of NSM may benefit from collection of
      oncologic data such as tumor-to-nipple distance and tumor location.

PMID- 24581995
TI  - Long-term prognostic value of mesorectal grading after neoadjuvant
      chemoradiotherapy for rectal cancer.
AB  - BACKGROUND: Mesorectal grading was reported to be a valuable prognostic factor in
      rectal cancer surgery. Previous studies were retrospective, and had short follow
      up. OBJECTIVE: To assess the long-term influence of total mesorectal excision
      quality on disease recurrence in mid and low rectal cancer patients who received
      preoperative neoadjuvant chemoradiotherapy (CRT) and postoperative chemotherapy.
      METHODS: One hundred twenty-one patients with rectal cancer had either low
      anterior resection or abdominoperineal resection. All patients received
      neoadjuvant CRT and postoperative chemotherapy. Main outcome measures included
      TNM staging, involvement of the circumferential resection margin (ICRM),
      mesorectal grading, local and systemic recurrences were recorded. RESULTS: Follow
      up was done for at least 5 years or up to disease recurrence whatever comes
      first. Mean follow-up time was 59.4 months. Twenty-nine patients had
      abdominoperineal resection and 92 had low anterior resection. About 7.5% had
      positive CRM which was significantly correlated with mesorectal grading. Grade 3
      mesorectal specimens were obtained in approximately 60% of patients, 27% had
      grade 2, and only 13% had grade 1 (poor) mesorectal specimens. Poorer mesorectal
      grading increased with APR and lower rectal tumors. Recurrences occurred in 20%
      of patients (40% in the first 2 years, 32% in the 3rd year, and 28% in the 4th
      and 5th years); factors affecting recurrence included lymphovascular invasion,
      ICRM, and N stage. Mesorectal grading was not a valuable prognostic factor for
      recurrence unless it resulted in ICRM. Recurrences occurred earlier with poorer
      mesorectal grade, yet this was not statistically significant. CONCLUSIONS:
      Mesorectal grading is a pathologic description that reflects the quality of
      surgery. However, in patients who received neoadjuvant CRT and postoperative
      chemotherapy, grading had no long-term prognostic value regarding recurrences
      unless it resulted in ICRM.

PMID- 24581996
TI  - Hypothermia decreases postoperative intra-abdominal adhesion formation.
AB  - BACKGROUND: Hypothermia may decrease postoperative intra-abdominal adhesion. We
      sought to determine the most suitable temperature for hypothermia for decreasing
      postoperative adhesion formation. METHODS: One hundred and twenty male BALB/c
      mice weighing 25 to 30 g were randomized into 5 groups: adhesion model with
      infusion of cold saline at (I) 15 degrees C; (II) 10 degrees C; or (III) 4
      degrees C; (IV) adhesion model without infusion of saline; and (V) sham operation
      without infusion of saline. Adhesion scores, incidence of adhesion, and serum
      cytokine levels were measured at postoperative days 1, 3, 7, and 14. RESULTS:
      Adhesion scores among groups I, II, and III did not differ significantly.
      Interleukin-6 was significantly decreased in groups I, II, and III, compared to
      the levels in groups IV and V (P < .05). Tumor necrosis factor-alpha levels in
      groups I and II were significantly decreased compared to those in groups III, IV,
      and V (P < .05). CONCLUSION: We suggest that 15 degrees C is the appropriate
      temperature for induction of hypothermia to decrease postoperative intra
      abdominal adhesion formation.

PMID- 24581997
TI  - Influence of intraocular astigmatism on the correction of myopic astigmatism by
      laser-assisted subepithelial keratectomy.
AB  - PURPOSE: To assess the influence of the origin of astigmatism on the correction
      of myopic astigmatism by laser-assisted subepithelial keratectomy (LASEK).
      SETTING: Ophthalmology Department, Eye and ENT Hospital, Shanghai, China. DESIGN:
      Prospective study. METHODS: Patients having LASEK to correct myopia or myopic
      astigmatism were divided into 2 groups according to their ocular residual
      astigmatism (ORA). Patients were examined preoperatively and 1 and 3 months
      postoperatively. The efficacy of LASEK was compared between those with and those
      without a significant amount of intraocular astigmatism. RESULTS: The study
      comprised 54 eyes of 54 patients. The mean index of success (ratio of magnitude
      of remaining uncorrected astigmatism to that of initial preoperative astigmatism)
      in the high ORA group (n=21) and low ORA group (n=33) was 0.85 and 0.48,
      respectively, 1 month after surgery (t=2.17, P=.04) and 0.88 and 0.32,
      respectively, 3 months after surgery (t=2.18, P=.04). The Zernike coefficient of
      horizontal coma, Z(3,+1), increased more after surgery in the high ORA group than
      in the low ORA group (1 month versus preoperative, t=2.32, P=.024; 3 months
      versus preoperative, t=2.07, P=.048). CONCLUSIONS: Nine percent and 2% of the
      eyes had minimal corneal haze at 1 month and 3 months, respectively. Laser
      assisted subepithelial keratectomy was less effective in correcting myopic
      astigmatism when astigmatism was mainly located at the internal optics.
      Horizontal coma increased more after LASEK in patients with higher ORA. FINANCIAL
      DISCLOSURE: No author has a financial or proprietary interest in any material or
      method mentioned.

PMID- 24581998
TI  - Preservation of enucleated porcine eyes for use in a wet laboratory.
AB  - PURPOSE: To design a method to preserve enucleated porcine eyes for use in a wet
      laboratory. SETTING: Laboratory of Experimental Ophthalmology, University Medical
      Center Groningen, the Netherlands. DESIGN: Experimental study. METHODS: Porcine
      eyes were preserved using 15 methods including salt solutions, anterior chamber
      infusion fluids, tap water, mineral water, air, and topical glycerol on the
      cornea. The central corneal thickness (CCT) was measured by A-scan ultrasound
      over 3 days. Differences between increases in CCT were compared using repeated
      measures multivariate analyses of variance. Also, lenses from eyes preserved in
      tap water were extracted and the lens epithelial cell morphology was studied.
      RESULTS: There was a significant interaction between the preservation method and
      CCT over 3 days (P<.001). Post hoc tests showed that the CCT in the sodium
      chloride (NaCl) 10.0% and tap-water groups increased significantly less than with
      4 other preservation methods. However, preservation in NaCl 10.0% resulted in
      unusable shrunken coriaceous lenses. Addition of glycerol did not decrease the
      CCT. Lens epithelial cells from eyes preserved in tap water for 48 hours appeared
      to be intact but lost cell organization. CONCLUSIONS: Of the 15 tested methods to
      preserve porcine eyes, tap water (mineral content 1.79 mmol/L) resulted in the
      least corneal swelling. It is not necessary to use more expensive anterior
      chamber infusion fluids or other salt solutions. FINANCIAL DISCLOSURE: Neither
      author has a financial or proprietary interest in any material or method
      mentioned.

PMID- 24581999
TI  - In vitro immunohistochemical and morphological observations of penetrating
      corneal incisions created by a femtosecond laser used for assisted intraocular
      lens surgery.
AB  - PURPOSE: To compare inflammatory cell response and morphological aspects of
      femtosecond laser-created corneal incisions. SETTING: Department of
      Ophthalmology, Goethe-University, Frankfurt am Main, Germany. DESIGN:
      Experimental study. METHODS: In 16 of 22 human corneoscleral buttons, clear
      corneal tunnel incisions were created using a femtosecond laser (Lensx) with 7
      MUJ laser pulse energy on the outer periphery and manually using a phaco knife on
      the respective opposite side (180 degrees). In 6 corneas, no treatment was
      performed (controls). Corneas were then kept in organ culture for 12 or 48 hours,
      and the inflammatory reaction was evaluated using standard immunofluorescence
      analyses for monocytes (CD11b) and for dendritic cells (HLA-DR). For
      morphological analyses and apoptosis, van Gieson staining and terminal
      deoxynucleotidyl transferase deoxy-UTP-nick end labeling was performed. RESULTS:
      There were no statistically significant differences in inflammatory cell response
      between femtosecond laser corneal incisions and manually performed incisions.
      Apoptosis was significantly more pronounced in the femtosecond incisions. The
      ratio of dendritic cells between femtosecond incisions and manual incisions was
      1:2 (12 hours and 48 hours; P=.07), the ratio of monocytes was 1:2 (12 hours and
      48 hours; P=.08), and the ratio of apoptotic cells was 1:5 (12 hours) and 1:6 (48
      hours) (P=.02). Femtosecond laser incisions showed a more sawtooth-like cutting
      edge than manual incisions. CONCLUSIONS: Femtosecond laser-created corneal
      incisions in human corneas showed no differences in inflammatory cell response
      but a significantly higher cell death rate than manually performed incisions,
      indicating an upregulated postoperative wound-healing response. FINANCIAL
      DISCLOSURE(S): Proprietary or commercial disclosures are listed after the
      references.

PMID- 24582000
TI  - Activated microglia do not form functional gap junctions in vivo.
AB  - We investigated whether microglia form gap junctions with themselves, or with
      astrocytes, oligodendrocytes, or neurons in vivo in normal mouse brains, and in
      pathological conditions that induce microglial activation - brain injury and a
      model of Alzheimer's disease. Although microglia are in close physical proximity
      to glia and neurons, they do not form functional gap junctions under these
      pathological conditions. 

PMID- 24582001
TI  - CSF levels of YKL-40 are increased in MS and replaces with immunosuppressive
      treatment.
AB  - The role of glial cells during different phases of multiple sclerosis (MS) is
      unclear. To monitor glial activation we analyzed the biomarkers YKL-40 and sCD14
      in cerebrospinal fluid (CSF) from MS patients during different disease phases and
      in response to immunosuppressive treatment. CSF levels of YKL-40 were increased
      in MS during relapse, remission and secondary progression compared with healthy
      controls. Furthermore, YKL-40 levels in CSF decreased by mitoxantrone and
      natalizumab treatment. No differences were observed in CSF levels of sCD14. Thus,
      we can infer that glial activation is present in all MS phases and decreases by
      immunosuppressive treatment. 

PMID- 24582002
TI  - A primary care based healthy-eating and active living education session for
      weight reduction in the pre-diabetic population.
AB  - AIMS: Many studies have demonstrated the effectiveness of primary prevention
      strategies in type 2 diabetes, however, questions remain around the feasibility
      of high resource, intensive interventions within a healthcare setting. We report
      the results of a dietitian-led pre-diabetes education session targeting healthy
      eating and active living as strategies for weight reduction. METHODS:
      Participants were asked to complete a baseline questionnaire prior to completing
      the pre-diabetes education session and were sent follow-up questionnaires at 3
      and 6 months. Differences between participants at baseline, 3 and 6 months were
      determined using chi(2), t-tests and ANOVA. RESULTS: Of the 211 participants
      asked to fill out baseline questionnaires, 45 participants completed
      questionnaires at baseline, 3 months and 6 months. Although we observed general
      trends towards improvements in diet, physical activity and weight related
      behaviours among the 45 completers, no significant changes were observed among
      participants between questionnaire periods. CONCLUSION: A "one-off", theory
      guided group education session may be insufficient to support lifestyle
      modifications in the context of weight management in a pre-diabetic population.
      Further evaluation of the efficacy and feasibility of the PCN as a setting for
      lifestyle intervention is required.

PMID- 24582003
TI  - Chronic Lyme disease: fact or fiction?

PMID- 24582004
TI  - Staging laparoscopy in patients scheduled for pancreaticoduodenectomy minimizes
      hospitalization in the remaining life time when metastatic carcinoma is found.
AB  - OBJECTIVE: To compare the burden of total hospitalization as a ratio of survival
      of staging laparoscopy versus prophylactic bypass surgery in patients with
      unresectable periampullary adenocarcinoma. BACKGROUND: Periampullary
      adenocarcinoma is an aggressive cancer with up to 35% of the patients at surgery
      found to be unresectable. Palliative prophylactic surgical bypass versus
      endoscopic stenting has been addressed by randomized controlled trials, but none
      reported on the burden of hospitalization. METHODS: From a prospective database
      all patients with periampullary adenocarcinomas with a preoperative patent
      biliary stent and absent gastric outlet obstruction, but found unresectable
      during surgery, were analysed. They underwent a staging laparoscopy only versus
      prophylactic palliative bypass surgery. In-hospital days of the initial admission
      as well as all consecutive admission days during the remaining life span were
      compared both in absolute numbers and as relative impact. RESULTS: The inclusion
      criteria were met by 205 patients. Of these 131 patients underwent a staging
      laparoscopy detecting metastases in 21 patients. In 184 laparotomies 54 patients
      underwent prophylactic palliative bypass surgery for unresectable disease. Median
      total in-hospital-stay in the Laparoscopy Group was 3 days versus 11 days in the
      Palliative Bypass Group (p = 0.0003). Patients with metastatic disease found
      during laparoscopy stayed 3.5% of the remaining life time in hospital vs. 10.0%
      (p = 0.029) in patients with metastatic disease who underwent bypass surgery.
      CONCLUSIONS: Staging laparoscopy and early discharge in patients with metastatic
      peri-ampullary carcinoma resulted in reduced hospitalization, both in absolute
      number of days and as a rate of survival time.

PMID- 24582005
TI  - Acquired autistic behaviors in children with mucopolysaccharidosis type IIIA.
AB  - OBJECTIVES: To assess autism spectrum disorder (ASD) behaviors in children with
      mucopolysaccharidosis type IIIA (MPS IIIA) using a standard measure, understand
      the behavioral evolution of the disease, and provide specific guidelines for
      diagnosis. STUDY DESIGN: Children (n = 21) with documented enzyme deficiency and
      SGSH gene mutations, cognitive age-equivalent >12 months, and early onset were
      administered the Autism Diagnostic Observation Schedule (ADOS) (module 1) and
      Bayley Scales of Infant Development-Third Edition. ADOS Social Affect and
      Restricted Repetitive Behavior total scores, as well as Bayley Scales of Infant
      Development-Third Edition cognitive age-equivalent scores, are reported using
      descriptive statistics and graphic presentations. RESULTS: Thirteen of the 21
      children evaluated met the ADOS criteria for ASD/autism. ADOS score was strongly
      associated with age; all 11 children aged >46 months met the criteria, compared
      with only 2 of 10 aged <46 months. Social and affective abnormalities were most
      frequent; restricted interests and repetitive behaviors were largely absent. Lack
      of cognitive growth paralleled ADOS score. CONCLUSION: An increased incidence of
      ASD-like social behaviors was seen at age 3-4 years in children with early-onset
      MPS IIIA. Although more frequent in the severely impaired children, ASD-like
      behaviors were observed across the entire range of cognitive impairment.
      Clinicians must be aware that when a child acquires ASD-like behaviors, MPS IIIA
      should be included in the differential diagnosis.

PMID- 24582006
TI  - Assessment of the outcomes associated with periprocedural anticoagulation
      management in children with acute lymphoblastic leukemia.
AB  - OBJECTIVE: To report the outcomes of an institutional protocol for periprocedural
      anticoagulant (AC) management in children with acute lymphoblastic leukemia
      (ALL). STUDY DESIGN: Children being treated for ALL who received full-dose
      (therapeutic) anticoagulation before undergoing at least 1 lumbar puncture (LP)
      were included in this retrospective cohort study. The main outcome was the risk
      of traumatic LP; exploratory analysis included the risks of symptomatic spinal
      hematoma and progression/recurrence of the thrombotic event. Analyses were
      conducted using logistic regression analysis with a generalized estimating
      equation approach. RESULTS: Twenty-two children with ALL receiving an AC
      underwent a total of 396 LPs. Although traumatic LP was associated with full-dose
      AC therapy in univariable analysis, a multiple logistic regression model
      controlling for other risk factors for traumatic LP showed that AC therapy was
      not significantly associated with the risk of traumatic LP when the ACs were held
      as per the institutional protocol. No patient developed symptomatic spinal
      hematoma. Exploratory analysis revealed that AC dose, a likely marker of thrombus
      burden, was significantly associated with progression/recurrence of the
      thrombotic event in univariable analysis. CONCLUSION: In our cohort, recent AC
      therapy was not statistically associated with an increased risk of bleeding after
      LP when following a specific protocol for periprocedural AC management. The risk
      associated with the progression/recurrence of thromboembolic events requires
      further evaluation.

PMID- 24582007
TI  - Remifentanil versus morphine-midazolam premedication on the quality of
      endotracheal intubation in neonates: a noninferiority randomized trial.
AB  - OBJECTIVE: To compare remifentanil and morphine-midazolam for use in nonurgent
      endotracheal intubation in neonates. STUDY DESIGN: In this prospective
      noninferiority randomized trial, newborns of gestational age >=28 weeks admitted
      in the neonatal intensive care unit requiring an elective or semielective
      endotracheal intubation were divided into 2 groups. One group (n = 36) received
      remifentanil (1 MUg/kg), and the other group (n = 35) received morphine (100
      MUg/kg) and midazolam (50 MUg/kg) at a predefined time before intubation
      (different in each group), to optimize the peak effect of each drug. Both groups
      also received atropine (20 MUg/kg). The primary outcome was to compare the
      conditions of intubation, and the secondary outcome was to compare the duration
      of successful intubation, physiological variables, and pain scores between groups
      for first and second intubation attempts. Adverse events and neurologic test data
      were reported. RESULTS: Intubation with remifentanil was not inferior to that
      with morphine-midazolam. At the first attempted intubation, intubation conditions
      were poor in 25% of the remifentanil group and in 28.6% of the morphine-midazolam
      group (P = .471). For the second attempt, conditions were poor in 28.6% of the
      remifentanil group, compared with 10% of the morphine-midazolam group (P = .360).
      The median time to successful intubation was 33 seconds (IQR, 24-45 seconds) for
      the remifentanil group versus 36 seconds (IQR, 25-59 seconds) for the morphine
      medazolam group (P = .359) at the first attempt and 45 seconds (IQR, 35-64
      seconds) versus 56 seconds (IQR, 44-68 seconds), respectively, for the second
      attempt (P = .302). No significant between-group difference was reported for
      hypotension, bradycardia, or adverse events. CONCLUSION: In our cohort,
      remifentanil was at least as effective as the morphine-midazolam regimen for
      endotracheal intubation. Thus, premedication using this very-short-acting opioid
      can be considered in urgent intubations and is advantageous in rapid extubation.

PMID- 24582009
TI  - Prevalence of Prader-Willi syndrome among infants with hypotonia.
AB  - OBJECTIVE: To investigate the prevalence of Prader-Willi syndrome (PWS) in
      infants with hypotonia between the ages of 0 and 2 years. STUDY DESIGN:
      Karyotyping studies were performed in all infants with hypotonia. The study group
      was composed of infants with hypotonia for whom the karyotyping was found to be
      normal. Fluorescence in situ hybridization and methylation analysis were
      performed simultaneously in the study group. Molecular studies for uniparental
      disomy were undertaken in the patients without deletions with an abnormal
      methylation pattern. RESULTS: Sixty-five infants with hypotonia with a mean age
      of 8 months were enrolled. A deletion was detected in 6 patients by fluorescence
      in situ hybridization analysis. Only 1 patient had no deletion but had an
      abnormal methylation pattern. A maternal uniparental disomy was observed in this
      patient. PWS was diagnosed in 10.7 % (7/65) of the infants with hypotonia.
      CONCLUSION: The prevalence of PWS syndrome is high among infants with hypotonia.
      PWS should be considered by pediatricians and neonatologists in the differential
      diagnosis of all newborns with hypotonia. Early diagnosis of PWS is important for
      the management of these patients.

PMID- 24582010
TI  - Parental history of adenotonsillectomy is associated with obstructive sleep apnea
      severity in children with snoring.
AB  - OBJECTIVE: To test the hypothesis that history of adenoidectomy and/or
      tonsillectomy (AT) in at least 1 of the parents during childhood, is a risk
      factor for moderate-to-severe obstructive sleep apnea (OSA) (apnea-hypopnea index
      [AHI] >5 episodes/hour) in the offspring with snoring. STUDY DESIGN: Data of
      children with snoring who were referred for polysomnography over 12 years by
      primary care physicians were reviewed. RESULTS: Data of 798 children without
      history of prior AT, neuromuscular, or genetic disorders or craniofacial
      abnormalities were analyzed. Of these children, 69.3% had tonsillar hypertrophy,
      25.8% were obese, 26.8% had at least 1 parent with history of AT, and 22.1% had
      AHI >5 episodes/hour. Parental history of AT was significantly associated with
      moderate-to-severe OSA (logit model including sex, tonsillar hypertrophy,
      obesity, and physician-diagnosed wheezing; OR [95% CI], 1.70 [1.18-2.46]; P <
      .01). When significant variables from the logit model (tonsillar hypertrophy,
      obesity, parental history of AT) were considered independently or in combination,
      tonsillar hypertrophy combined with history of AT in at least 1 of the parents
      had high specificity (84.4%) and the highest positive likelihood ratio (1.78) for
      identifying children with AHI >5 episodes/hour. CONCLUSIONS: Among children with
      snoring who are referred for polysomnography by primary care physicians, those
      with tonsillar hypertrophy and parental history of AT have increased risk of
      moderate-to-severe OSA and represent 1 of the subgroups that should be
      prioritized for a sleep study in settings with limited resources.

PMID- 24582011
TI  - Preferential cephalic redistribution of left ventricular cardiac output during
      therapeutic hypothermia for perinatal hypoxic-ischemic encephalopathy.
AB  - OBJECTIVE: To determine the relationship between left ventricular cardiac output
      (LVCO), superior vena cava (SVC) flow, and brain injury during whole-body
      therapeutic hypothermia. STUDY DESIGN: Sixteen newborns with moderate or severe
      hypoxic-ischemic encephalopathy were studied using echocardiography during and
      immediately after therapeutic hypothermia. Measures were also compared with 12
      healthy newborns of similar postnatal age. Newborns undergoing therapeutic
      hypothermia also had cerebral magnetic resonance imaging as part of routine
      clinical care on postnatal day 3-4. RESULTS: LVCO was markedly reduced (mean +/-
      SD 126 +/- 38 mL/kg/min) during therapeutic hypothermia, whereas SVC flow was
      maintained within expected normal values (88 +/- 27 mL/kg/min) such that SVC flow
      represented 70% of the LVCO. The reduction in LVCO during therapeutic hypothermia
      was mainly accounted by a reduction in heart rate (99 +/- 13 vs 123 +/- 17
      beats/min; P < .001) compared with immediately postwarming in the context of
      myocardial dysfunction. Neonates with brain injury on magnetic resonance imaging
      had higher SVC flow prerewarming, compared with newborns without brain injury (P
      = .013). CONCLUSION: Newborns with perinatal hypoxic-ischemic encephalopathy
      showed a preferential systemic-to-cerebral redistribution of cardiac blood flow
      during whole-body therapeutic hypothermia, which may reflect a lack of cerebral
      vascular adaptation in newborns with more severe brain injury.

PMID- 24582008
TI  - Prevalence of and disparities in barriers to care experienced by youth with type
      1 diabetes.
AB  - OBJECTIVE: To describe the prevalence of access and process barriers to health
      care and to examine their relationship to sociodemographic and disease factors in
      a large and diverse cohort of US youth with type 1 diabetes. STUDY DESIGN: A
      cross-sectional analysis of 780 youth who participated in the SEARCH for Diabetes
      in Youth Study and were diagnosed with type 1 diabetes in 2002-2005. Experience
      of barriers to care was collected from parent report on questionnaires. Analyses
      included multivariate regression models to predict the presence of specific
      barriers to care. RESULTS: Overall, 81.7% of participants reported at least one
      barrier; the 3 most common were costs (47.5%), communication (43.0%), and getting
      needed information (48.4%). Problems with access to care, not having a regular
      provider, and receiving contextual care (care that takes into account personal
      and family context) were associated with poorer glycated hemoglobin levels.
      Adjusted multivariate models indicated that barriers related to access (regular
      provider, cost) were most likely for youth with low family income and those
      without public health insurance. Barriers associated with the processes of
      quality care (contextual care, communication) were more likely for Hispanic youth
      and those whose parents had less education. CONCLUSIONS: This study indicates
      that a large proportion of youth with type 1 diabetes experience substantial
      barriers to care. Barriers to access and those associated with processes of
      quality care differed by sociodemographic characteristics. Future investigators
      should expand knowledge of the systemic processes that lead to disparate outcomes
      for some youth with diabetes and assess potential solutions.

PMID- 24582012
TI  - Salvage operations for patients with persistent or recurrent cancer of the
      maxillary sinus after superselective intra-arterial infusion of cisplatin with
      concurrent radiotherapy.
AB  - Our aim was to evaluate the feasibility of salvage operations for patients with
      persistent or recurrent cancer of the maxillary sinus after superselective intra
      arterial infusion of cisplatin with concurrent radiotherapy. We retrospectively
      analysed the records of 61 patients with cancer of the maxillary sinus who were
      treated in this way. Chemotherapy comprised 100-120 mg/m(2) superselective intra
      arterial infusions of cisplatin given a median of 4 times weekly (range 2-5).
      Concurrent radiotherapy was given in a median dose of 65 Gy (range 24-70 Gy).
      Persistent or recurrent cancer of the maxillary sinus was found in 17 patients,
      of whom 11 had salvage surgery. The disease was controlled in 8 of the 11, and 7
      of the 11 survived with no evidence of disease. Their 5-year overall survival was
      61%. Two of the 11 developed serious operative complications. Salvage surgery for
      patients with persistent or recurrent cancer of the maxillary sinus treated by
      superselective chemoradiotherapy is both safe and successful. Salvage surgery is
      a good option when this sort of persistent or recurrent cancer is followed up
      after the regimen of chemoradiotherapy described.

PMID- 24582014
TI  - Aging gracefully: your American Journal of Orthodontics & Dentofacial
      Orthopedics, 1915 to 2015.

PMID- 24582013
TI  - Effect of antiresorptive drugs on bony turnover in the jaw: denosumab compared
      with bisphosphonates.
AB  - Osteonecrosis of the jaw as a result of treatment with receptor activators of
      nuclear factor kappa-B ligand (RANKL) inhibitors (denosumab) is a new type of
      bony necrosis, the exact pathogenesis of which is unknown. Our aim was to find
      out whether the turnover of bone in the jaw is increased after denosumab has been
      given compared with other skeletal sites, and if that turnover might have a role
      in denosumab-related osteonecrosis of the jaw (DRONJ). Bone scintigraphic images
      of 45 female patients with breast cancer and bone metastases were analysed
      retrospectively, and divided into 3 groups: those given denosumab, those given a
      bisphosphonate, and a control group (n=15 in each). All patients had bone
      scintigraphy before treatment (T0) and during the course of treatment after 12
      (T1) and 24 (T2) months. The data were analysed quantitatively using 6 preset
      bony regions of interest. There was similar turnover of bone in the mandible
      compared with other skeletal sites (such as the femur), while the maxilla showed
      significantly higher turnover. None of the bony regions investigated showed any
      significant changes after the bisphosphonate had been given. There was a tendency
      to increase bone turnover in those patients taking denosumab. The bone turnover
      of the jawbone is not overtly changed either by a bisphosphonate or denosumab, so
      it seems unlikely that oversuppression of bony turnover in the jawbones plays an
      important part either in the pathogenesis of DRONJ or in the bisphosphonate
      related osteonecrosis of the jaw (BRONJ). 

PMID- 24582015
TI  - Effect of micro-osteoperforations.

PMID- 24582016
TI  - Effect of micro-osteoperforations. Authors' response.

PMID- 24582017
TI  - It takes courage.

PMID- 24582019
TI  - Effect of visual method vs plaque disclosure in enhancing oral hygiene in
      adolescents and young adults: a single-blind randomized controlled trial.
AB  - INTRODUCTION: Enamel demineralization and gingival inflammation are the most
      prevalent consequences of biofilm formation in orthodontics. Our hypothesis was
      that educating patients about the severe consequences of biofilm accumulation
      could enhance their oral hygiene while wearing fixed appliances. METHODS: This
      study was designed as a randomized controlled 4-arm parallel trial. A total of
      148 participants in Chengdu, China, matching the eligibility criteria of 11 to 25
      years of age, at least 20 natural teeth, and a treatment plan that included
      conventional stainless steel brackets, were randomly assigned to 4 intervention
      groups based on computer-generated random sequencing using simple randomization
      without blocking. In group A (n = 37), the subjects were shown images
      illustrating the severe consequences of biofilm formation, including enamel
      demineralization and gingival inflammation; subjects in group B (n = 40) were
      given biofilm disclosing tablets; those in group C (n = 38) received a
      combination of A and B; the subjects in group D (n = 33) served as the controls.
      The investigators were blinded to the allocations, and the researcher managing
      the random sequence did not participate in allocation or measurement. All groups
      received routine oral hygiene instructions. Plaque index and gingival index
      scores were recorded at each appointment during a 6-month follow-up. RESULTS:
      Eighteen participants were lost during follow-up, resulting in a total of 130
      participants after the trial (group A, 35; group B, 32; group C, 34; group D,
      29). No adverse events were recorded. Groups A and C exhibited a significantly
      lower plaque index scores (parameter-estimate [95% confidence interval] = -1.20 [
      1.76 to -0.63] for group A, and -1.12 [-1.69 to -0.56] for group C) and gingival
      index scores (-0.13 [-0.21 to -0.04], and -0.19 [-0.28 to -0.10]), respectively,
      compared with group D (P <0.001 for all), whereas no significant difference was
      found between groups B and D, or between groups A and C (P >0.05). The adults had
      significantly lower plaque index (0.48 [0.13-0.84], P <0.001) and gingival index
      (0.06 [0.01-0.11], P = 0.018) scores than did the teenagers, and the female
      subjects had significantly higher gingival index (-0.06 [-0.11 to -0.01], P =
      0.040) scores than did the male subjects. CONCLUSIONS: The use of images showing
      the severe consequences of biofilm accumulation enhanced the oral hygiene of
      patients treated with fixed appliances.

PMID- 24582020
TI  - Adult orthodontic patients' views regarding dentofacial normality: a qualitative
      study.
AB  - INTRODUCTION: The concept of normality in orthodontic diagnosis and treatment is
      defined from the clinicians' point of view or derived from concepts developed
      from observation of "ideal" persons. In-depth appreciation of what a patient
      views as normal is paramount for effective shared decision making. In this study,
      we aimed to examine the concept of dentofacial normality in orthodontics from the
      patient's perspective. METHODS: This was a qualitative study of adults attending
      for orthodontic consultations at a teaching hospital. Semistructured interviews
      were conducted until data saturation occurred (n = 15). The data were managed
      using a framework approach, and recurrent themes were identified. RESULTS: Three
      main themes were identified in the interviews: the components of dentofacial
      normality, the impact of dentofacial abnormality, and factors influencing
      patients' conceptualization of dentofacial normality. The components of normal
      appearance are apparent in the views of potential adult orthodontic patients.
      These ideas are formed from personal observations in conjunction with the
      external influences of family, friends, and the commercial media. There was a
      biopsychosocial impact of dentofacial abnormality with both enacted and felt
      stigma playing substantial roles. CONCLUSIONS: A normal dentofacial appearance
      cannot be solely constructed from measureable biologic variables. Patients view
      normality in terms of features that are acceptable biologically, psychologically,
      and socially, and there is significant overlap in these domains. Clinicians
      should be aware that traditionally held concepts of what they believe to be
      normal or abnormal might not fully represent patients' beliefs.

PMID- 24582021
TI  - Maxillary arch width and buccal corridor changes with orthodontic treatment. Part
      2: attractiveness of the frontal facial smile in extraction and nonextraction
      outcomes.
AB  - INTRODUCTION: This study was designed to assess the influence that the buccal
      corridor might have on the frontal facial attractiveness of subjects who had
      received orthodontic treatment with or without 4 premolar extractions. METHODS:
      Posttreatment full-face frontal smiling photographs of 30 premolar extraction and
      27 nonextraction patients were evaluated by 20 orthodontists, 20 dentists, and 20
      laypeople using a visual analog scale. The ratings were analyzed according to
      rater group, rater sex, and number of years in practice for orthodontists and
      dentists to search for any statistically significant differences in the ratings
      on the basis of treatment groups, subject sex, and buccal corridor widths and
      areas. RESULTS: Orthodontists and dentists gave higher mean overall frontal
      facial attractiveness scores than did laypeople. There were no significant
      differences in how men and women rated the study subjects. The number of years in
      practice did not affect how the orthodontists rated, but it did affect the
      ratings of the dentists. Female subjects were consistently rated as significantly
      more attractive than male subjects. There was no difference in ratings for the
      extraction and nonextraction subject groups. The buccal corridor widths and areas
      did not affect the frontal facial attractiveness ratings. CONCLUSIONS: If
      treatment has been carried out with thorough diagnosis and careful planning,
      neither the choice of extraction or nonextraction treatment, nor the resulting
      buccal corridor widths or areas appeared to affect the subjects' frontal facial
      attractiveness.

PMID- 24582023
TI  - Dentoalveolar compensation according to skeletal discrepancy and overjet in
      skeletal Class III patients.
AB  - INTRODUCTION: This study was designed to investigate dentoalveolar compensation
      in untreated skeletal Class III patients with either positive or negative
      overjet. METHODS: The positive overjet groups consisted of 104 adults, divided
      into group 1 (angle between sella-nasion to mandibular plane (SN-MP) > 38 degrees
      , n = 30), group 2 (30 degrees  < SN-MP < 38 degrees , n = 43), and group 3 (SN
      MP <30 degrees , n = 31). The negative overjet groups (groups 4-6) consisted of
      90 adults who were closely matched to the positive overjet groups with regard to
      the ANB and SN-MP angles. Twenty-two cephalometric measurements were compared
      between the matched groups. In the positive overjet groups, correlation analysis
      was performed between the skeletal and dental measurements, and regression
      analysis was performed to determine the incisor-mandibular plane angle. RESULTS:
      The maxillary incisors were more proclined and the occlusal plane was more
      flattened in the positive overjet groups than in the negative overjet groups;
      however, there was no statistically significant difference between them with
      regard to mandibular incisor inclination. The inclinations of the maxillary and
      mandibular incisors were correlated with both the sagittal and vertical skeletal
      measurements. Eight regression equations for the incisor-mandibular plane angle
      were calculated with the highest coefficient of determination of 0.547.
      CONCLUSIONS: Proclination of the maxillary incisors and flattening of the
      occlusal plane contributed to a positive overjet. Mandibular incisor inclination
      was more closely associated with sagittal and vertical skeletal discrepancies and
      was not affected by the incisal relationship.

PMID- 24582022
TI  - Phenotypic diversity in white adults with moderate to severe Class II
      malocclusion.
AB  - INTRODUCTION: Class II malocclusion affects about 15% of the population in the
      United States and is characterized by a convex profile and occlusal disharmonies.
      The specific etiologic mechanisms resulting in the range of Class II
      dentoskeletal combinations observed are not yet understood. Most studies
      describing Class II phenotypic diversity have used moderate sample sizes or
      focused on younger patients who later in life might outgrow their Class II
      discrepancies; such a focus might also preclude the visualization of adult Class
      II features. The majority have used simple correlation methods resulting in
      phenotypes that might not be generalizable to different samples and thus might
      not be suitable for studies of malocclusion etiology. The purpose of this study
      was to address these knowledge gaps by capturing the maximum phenotypic
      variations in a large sample of white Class II subjects selected with strict
      eligibility criteria and rigorously standardized multivariate reduction analyses.
      METHODS: Sixty-three lateral cephalometric variables were measured from the
      pretreatment records of 309 white Class II adults (82 male, 227 female; ages, 16
      60 years). Principal component analysis and cluster analysis were used to
      generate comprehensive phenotypes to identify the most homogeneous groups of
      subjects, reducing heterogeneity and improving the power of future malocclusion
      etiology studies. RESULTS: Principal component analysis resulted in 7 principal
      components that accounted for 81% of the variation. The first 3 components
      represented variation on mandibular rotation, maxillary incisor angulation, and
      mandibular length. The cluster analysis identified 5 distinct Class II
      phenotypes. CONCLUSIONS: A comprehensive spectrum of Class II phenotypic
      definitions was obtained that can be generalized to other samples to advance our
      efforts for identifying the etiologic factors underlying Class II malocclusion.

PMID- 24582024
TI  - Molar heights and incisor inclinations in adults with Class II and Class III
      skeletal open-bite malocclusions.
AB  - INTRODUCTION: The aim of this research was to compare maxillary and mandibular
      molar heights and incisor inclinations in patients with skeletal open-bite Class
      II, patients with skeletal open-bite Class III, and an untreated control group.
      METHODS: Pretreatment lateral cephalograms of 70 orthodontic patients (34 men, 36
      women) between 16 and 40 years of age were examined. The sample was divided into
      3 groups according to facial growth pattern and overbite. The control group (n =
      25) included normodivergent Class I subjects with adequate overbite; the skeletal
      open-bite Class II group (n = 25) and the skeletal open-bite Class III group (n =
      20) included hyperdivergent Class II or Class III subjects with negative
      overbite. Measurements considered were ANB angle, palatal and mandibular plane
      angles, maxillary incisor palatal plane angulation, and mandibular incisor
      mandibular plane angulation, as well as the distance from the palatal or the
      mandibular plane to the mesial cusp of the molars. Multivariate analysis of
      covariance and multivariate analysis of variance tests were used to determine the
      differences between the groups, followed by the Tukey post-hoc test.
      Additionally, the Mann-Whitney U test and Kruskall-Wallis test were performed.
      RESULTS: Significant differences in molar height were found (P <0.001). A 4-mm
      difference in maxillary molar height between the skeletal open-bite and control
      groups was found. Mandibular molar height was greater in the skeletal open-bite
      Class II group (P <0.001). Maxillary incisor palatal plane angulation was greater
      in the skeletal open-bite Class III group by approximately 6 degrees . Mandibular
      incisor to mandibular plane angulation was 10 degrees  more lingual in the
      skeletal open-bite Class III group (P <0.001). CONCLUSIONS: The skeletal open
      bite groups had greater molar heights than did the control group. The skeletal
      open-bite Class II group had more eruption of the mandibular molars. The
      maxillary incisors were more proclined and the mandibular incisors were more
      lingual in the skeletal open-bite Class III group.

PMID- 24582025
TI  - Implant site development in the distal region of the mandible: bone formation and
      its stability over time.
AB  - INTRODUCTION: The purpose of this study was to determine the dimensional changes
      that occur in the alveolar ridge of patients upon distalization of the mandibular
      first premolars into the place of congenitally missing mandibular second
      premolars. The amount of bone formation that accompanied orthodontic treatment
      and the long-term stability of the new bone were assessed. METHODS: Fifty-five
      patients were included in the study, representing 71 congenitally missing
      mandibular second premolars. The dimensional changes were evaluated by comparing
      the dental stone casts and panoramic radiographs taken at treatment initiation
      (T1) and end (T2) and at follow-ups of 2 years (T3A) and 5 years (T3B). RESULTS:
      During the treatment period (T1-T2), the alveolar ridge width increased by an
      average of 28.5%, and the height increased by an average of 1.1 mm. During the
      retention periods (T2-T3A, T2-T3B), the alveolar ridge decreased by an average of
      4.2%, but the height decreased only slightly (by an average of 0.07 mm).
      CONCLUSIONS: Orthodontic tooth movement created a significant amount of new bone
      that was stable in both the horizontal and vertical directions.

PMID- 24582026
TI  - Soft-tissue profile growth in patients with repaired complete unilateral cleft
      lip and palate: A cephalometric comparison with normal controls at ages 7, 11,
      and 18 years.
AB  - INTRODUCTION: In this retrospective longitudinal study, we aimed to study
      differences in the soft-tissue profiles in growing children with clefts in
      comparison with controls through the period of facial growth from 7 to 18 years.
      METHODS: Lateral cephalometric measurements made at 7 years (T1), 11.1 years
      (T2), and 17.9 years (T3) of age of 70 white children (35 boys, 35 girls) with
      complete unilateral cleft lip and palate (UCLP) who received primary lip and
      palate repair surgeries at The Hospital for Sick Children, Toronto, were compared
      with those of a control group of similar ages, sexes, and racial backgrounds, and
      having skeletal Class I facial growth, selected from the Burlington Growth Study.
      None of the included subjects had received any surgeries other than the primary
      lip and palate repairs, and none had undergone nasal septum surgery or nasal
      molding during infancy. Between-group comparisons were made at each time point
      using generalized linear models adjusted for age and sex effects. Longitudinal
      comparisons across all time points were conducted using the mixed model approach,
      adjusting for these effects and their interactions with time. RESULTS:
      Bimaxillary retrognathism, progressive maxillary retrognathism, and increasing
      lower anterior face height with downward and backward growth rotation of the
      mandible in the UCLP group were seen. Unlike the hard-tissue face height ratio,
      their soft-tissue face height ratio was not affected. The upper lips in the UCLP
      group were shorter by 1.81 mm at T2 (P <0.001) and by 1.16 mm at T3 (P = 0.018),
      whereas their lower lips were 2.21 mm longer at T3 (P = 0.003). A reduced upper
      lip to lower lip length ratio at T2 and T3 (P <0.001) resulted. Their upper lips
      were relatively retruded by 1.44 mm at T1, 1.66 mm at T2, and 1.86 mm at T3 (all,
      P <0.001), and their lower lips were relatively protruded by 1.07 mm at T1 (P =
      0.003), 1.40 mm at T2 (P <0.001), and 1.62 mm at T3 (P <0.001). Nose depths in
      the UCLP group were shallower by at least 1 mm from T1 to T3, and columellar
      length was shorter by almost 2 mm (all, P <0.001). Their columellae and nose tips
      rotated downward with growth, with the most significant rotations experienced
      from T2 to T3, and progressive reductions in their soft-tissue profile convexity
      were seen from T1 to T3 (P <0.001). CONCLUSIONS: Key attributes of the imbalance
      in the soft-tissue profile in children with repaired UCLP were identified in the
      lip and nose regions. Although many profile differences were visible as early as
      7 years of age, they became more apparent by 11 years of age and increased in
      severity thereafter. The short upper lip combined with a long lower lip resulted
      in the characteristic lip length imbalance, whereas the progressively retruding
      upper lip and protruding lower lip led to developing a step relationship in the
      sagittal lip profile during the adolescent growth period. Their columellae and
      nose tips rotated downward during this time.

PMID- 24582027
TI  - Cervical vertebral column morphology and head posture in preorthodontic patients
      with anterior open bite.
AB  - INTRODUCTION: Cervical vertebral column morphology and head posture were examined
      and related to craniofacial morphology in preorthodontic children and adolescents
      with anterior open bite. METHODS: One hundred eleven patients (ages, 6-18 years)
      with an anterior open bite of more than 0 mm were divided into 2 groups of
      skeletal or dentoalveolar open bite. The skeletal open-bite group comprised 38
      subjects (19 girls, 19 boys). The dentoalveolar open-bite group comprised 73
      subjects (43 girls, 30 boys). Visual assessment of the cervical column and
      measurements of craniofacial morphology and head posture were made on profile
      radiographs. RESULTS: Deviations in the cervical vertebral column morphology
      occurred in 23.7% of the subjects in the skeletal open-bite group and in 19.2% in
      the dentoalveolar open-bite group, but the difference was not significant. Head
      posture was significantly more extended in the skeletal open-bite group compared
      with the dentoalveolar open-bite group (craniovertical angle [Mx/VER], P <0.05;
      craniocervical angles [Mx/OPT, Mx/CVT], P <0.01. Only head posture was associated
      with craniofacial morphology: extended posture was associated with a large
      cranial base angle (P <0.01, P <0.001), large vertical craniofacial dimensions (P
      <0.05; P <0.01; P <0.001), and retrognathia of the jaws (P <0.001). CONCLUSIONS:
      Cervical column morphology is described for the first time in children and
      adolescents with open bite. No significant differences in the cervical vertebral
      column's morphologic deviations were found between the skeletal and the
      dentoalveolar open-bite groups. Significant differences were found in head
      posture between the groups and with regard to associations with craniofacial
      dimensions. This might indicate a respiratory etiologic component in children
      with anterior open bite.

PMID- 24582028
TI  - Orthodontic decompensation and correction of skeletal Class III malocclusion with
      gradual dentoalveolar remodeling in a growing patient.
AB  - An 8-year-old girl with a skeletal Class III malocclusion was treated in 2
      phases. Maxillary expansion and protraction were carried out as the early
      intervention. However, her maxillary hypoplasia and mandibular hyperplasia
      deteriorated with age. The phase 2 comprehensive treatment began with proper
      mechanics when she was 12 years old with growth potential. In the maxillary arch,
      an auxiliary rectangular wire was used with a round main wire and an opening
      spring to create space for the impacted teeth and to bodily move the anterior
      teeth forward. Decompensation of mandibular incisors and correction of the Class
      III malocclusion were achieved by short Class III elastics with light forces and
      a gentle interaction between the rectangular wires and the lingual root-torque
      slots. The phase 2 active treatment period was 4 years 8 months. The 2-year
      follow-up indicated that our treatment results were quite stable. 

PMID- 24582029
TI  - Interdisciplinary treatment of a patient with bilateral cleft lip and palate and
      congenitally missing and transposed teeth.
AB  - The comprehensive treatment of a patient with cleft lip and palate requires an
      interdisciplinary approach for functional and esthetic outcomes. A 20-year-old
      woman with bilateral cleft lip and palate had a chief complaint of unesthetic
      appearance of her teeth and the presence of oronasal fistulae. Her clinical and
      radiographic evaluation showed a dolichofacial growth pattern, a Class II
      skeletal relationship with retroclined maxillary central incisors, 5 mm of
      negative overjet, maxillary constriction, maxillary and mandibular crowding,
      congenitally missing maxillary right incisors and left lateral incisor, and a
      transposed maxillary left canine. Her treatment plan included the extraction of 3
      premolars, maxillary expansion, segmental maxillary osteotomy, repair of the
      oronasal fistulae, rhinoplasty, periodontal surgery, and prosthodontic
      rehabilitation. To obtain a better occlusion and reduce the dimensions of the
      fistulae, orthognathic surgery comprising linear and rotational movements of the
      maxillary segments (premaxilla, right and left maxillary alveolar segments) in
      all 3 axes was planned by performing 3-dimensional virtual surgery on 3
      dimensional computerized tomography. At the end of the interdisciplinary
      treatment, a functional occlusion, a harmonious profile, and patient satisfaction
      were achieved. Posttreatment records after 1 year showed stable results. 

PMID- 24582030
TI  - Mandibular permanent first molars and incisors as predictors of mandibular
      permanent canine and premolar widths: applicability and consistency of the
      method.
AB  - INTRODUCTION: Estimating the mesiodistal widths of the mandibular permanent
      canines and premolars is an essential aspect of mixed dentition analysis. A
      method is proposed to predict the sum of the mandibular permanent canine and
      premolar widths based on the sum of the mandibular permanent first molars and
      incisors. In this study, we aimed to test the applicability and reliability of
      this method in a population in Belo Horizonte, Minas Gerais, Brazil. The methods
      of Moyers and of Tanaka and Johnston were also tested. METHODS: The sample
      consisted of 200 orthodontic study models, obtained from white Brazilian patients
      (123 female, 77 male). The mesiodistal widths of the teeth were measured with an
      analog caliper. Paired Student t tests with a significance level of 5% were used
      to compare the actual and predicted values. RESULTS: No statistically significant
      differences were found between the predicted and actual values of the sum of the
      mandibular permanent canine and premolar widths when using the new method. The
      differences were 0.6 mm for the male sample, 0.5 mm for the female sample, and
      0.6 mm for the total sample; the standard deviations were 1.9, 2.1, and 2.2 mm,
      respectively. However, overestimated predicted values with differences of 1.4 and
      1.9 mm (male and female) in the Moyers method and 1.9 and 3.3 mm (male and
      female) in the Tanaka and Johnston method were found. CONCLUSIONS: The new method
      is consistent and applicable to the population of Belo Horizonte. The other 2
      methods tended to overestimate the actual values of the permanent canines and
      premolars.

PMID- 24582031
TI  - Monitoring of typodont root movement via crown superimposition of single cone
      beam computed tomography and consecutive intraoral scans.
AB  - INTRODUCTION: The purpose of this study was to develop a new methodology to
      visualize in 3 dimensions whole teeth, including the roots, at any moment during
      orthodontic treatment without the need for multiple cone-beam computed tomography
      (CBCT) scans. METHODS: An extraoral typodont model was created using extracted
      teeth placed in a wax base. These teeth were arranged to represent a typical
      malocclusion. Initial records of the malocclusion, including CBCT and intraoral
      surface scans, were taken. Threshold segmentation of the CBCT was performed to
      generate a 3-dimensional virtual model. This model and the intraoral surface scan
      model were superimposed to generate a complete set of digital composite teeth
      composed of high-resolution surface scan crowns sutured to the CBCT roots. These
      composite teeth were individually isolated from their respective arches for
      single-tooth manipulations. Orthodontic treatment for the malocclusion typodont
      model was performed, and posttreatment intraoral surface scans before and after
      bracket removal were taken. A CBCT scan after bracket removal was also obtained.
      The isolated composite teeth were individually superimposed onto the
      posttreatment surface scan, creating the expected root position setup. To
      validate this setup, it was compared with the posttreatment CBCT scan, which
      showed the true positions of the roots. Color displacement maps were generated to
      confirm accurate crown superimpositions and to measure the discrepancies between
      the expected and the true root positions. RESULTS: Color displacement maps
      through crown superimpositions showed differences between the expected and true
      root positions of 0.1678 +/- 0.3178 mm for the maxillary teeth and 0.1140 +/-
      0.1587 mm for the mandibular teeth with brackets. Once the brackets were removed,
      differences of 0.1634 +/- 0.3204 mm for the maxillary teeth and 0.0902 +/- 0.2505
      mm for the mandibular teeth were found. CONCLUSIONS: A new reliable approach was
      demonstrated in an ex-vivo typdont model to have the potential to track the 3
      dimensional positions of whole teeth including the roots, with only the initial
      CBCT scan and consecutive intraoral scans. Since the presence of brackets in the
      intraoral scan had a minimal influence in the analysis, this method can be
      applied at any stage of orthodontic treatment.

PMID- 24582032
TI  - Measures of frequency of disease.

PMID- 24582033
TI  - Preservation or division of the intercostobrachial nerve in axillary dissection
      for breast cancer: meta-analysis of randomised controlled trials.
AB  - PURPOSE: Management of the ICBN during axillary dissection is controversial and
      the division of ICBN is often trivialised. The effect of dividing the ICBN, and
      its association with sensory disturbance, is unclear. A systematic review and
      meta-analysis was performed to evaluate the effect of preserving the ICBN during
      axillary dissection. METHODS: A systematic literature review and meta-analysis is
      performed according to the PRISMA and Cochrane Collaboration guidelines. RESULTS:
      Three RCTs and four non-RCTs were reviewed. A meta-analysis demonstrated that the
      incidence of sensory disturbance was significantly lower with preservation of
      ICBN compared to division of the ICBN with Mantel-Haenzel combined odds ratio
      0.31 (0.17-0.57, 95% CI). There was relatively low level of heterogeneity (I(2) =
      19%, chi(2) = 2.48, df = 2). The sensory disturbance was more likely to be
      hyposensitivity when compared to hypersensitivity (p < 0.0001). No difference on
      number of lymph nodes dissected or operating time was noted. CONCLUSION: This
      meta-analysis demonstrates that division of the ICBN is associated with higher
      risk of sensory disturbance, and that the nature of this sensory disturbance is
      more likely to be hyposensitivity, attributable to reduced nerve function.

PMID- 24582034
TI  - Impact of exposure of crude oil and dispersant (COREXIT(r) EC 9500A) on
      denitrification and organic matter mineralization in a Louisiana salt marsh
      sediment.
AB  - In response to the 2010 oil spill from the explosion of the Deepwater Horizon oil
      rig in the Gulf of Mexico, this experiment aims to study the ecological impact of
      the crude oil and dispersant (COREXIT(r) EC 9500A) in a coastal salt marsh
      ecosystem. The marsh sediment was incubated under an anaerobic condition with
      exposure to the crude oil or/and dispersant. The experiments were conducted in
      two continuous phases of nitrate addition to study denitrification potential
      using acetylene blockage technique and organic matter mineralization potential
      indicated by CO2 production in the sediment. Results show that the oil slightly
      (with no statistical significance p>0.05) increased both the denitrification and
      organic matter mineralization activities, likely due to oil components serving as
      additional organic matter. In contrast, the dispersant significantly (p<0.05)
      inhibited denitrification, but stimulated organic matter mineralization
      activities in the sediment due to unknown mechanisms. As a consequence, redox
      potentials (Eh) were much lower in the dispersant treated systems. The ecological
      impacts from the dispersant exposure may come from two fronts. First, loss of
      organic matter from the coastal marsh will threaten the long-term stability of
      the ecosystem, and the decrease in denitrification activity will weaken the N
      removal efficiency. Secondly, more reducing conditions developed by the
      dispersant exposure will likely preserve the oil in the ecosystem for an extended
      period of time due to weaker oil biodegradation under anaerobic conditions. 

PMID- 24582035
TI  - Relations between total mercury, methylmercury and selenium in five tissues of
      Sepia officinalis captured in the south Portuguese coast.
AB  - Mercury, methylmercury and selenium were determined in digestive gland, branchial
      hearts, mantle, kidney and gills of Sepia officinalis from two areas of the south
      Portuguese coast. To the best of our knowledge these are the first data on Hg,
      MeHg and Se in branchial hearts, kidney and gills of cuttlefish. Digestive gland,
      branchial hearts and kidney presented higher levels of Hg and Se than mantle and
      gills. Methylmercury was significantly higher in digestive gland, branchial
      hearts and mantle. The enhanced levels of Hg in digestive gland and branchial
      heart reinforce the elevated storage capacity of these two tissues. The
      percentage of MeHg varied from 6.1% in gills to 92% in mantle. Linear and
      positive MeHg-Hg relations were obtained for the five tissues, being the better
      relation and higher slope observed for mantle, followed by branchial hearts,
      digestive gland, kidney and gills. The Se:Hg molar ratios showed a surplus of Se
      in all tissues. Calculations based on the equimolarity of Se:Hg point that 95-99%
      of Se are not linked to Hg (Se free). The negligible quantity of Se associated
      with Hg suggests that the mechanism of MeHg demethylation was not triggered in
      none of the tissues, presumably because the threshold for MeHg toxicity was not
      achieved. 

PMID- 24582036
TI  - Cytotoxicity of binary mixtures of human pharmaceuticals in a fish cell line:
      approaches for non-monotonic concentration-response relationships.
AB  - Predicting the effects of mixtures of environmental micropollutants is a priority
      research area. In this study, the cytotoxicity of ten pharmaceuticals to the
      rainbow trout cell line RTG-2 was determined using the neutral red uptake assay.
      Fluoxetine (FL), propranolol (PPN), and diclofenac (DCF) were selected for
      further study as binary mixtures. Biphasic concentration-response relationships
      were observed in cells exposed to FL and PPN. In the case of PPN, microscopic
      examination revealed lysosomal swelling indicative of direct uptake and
      accumulation of the compound. Three equations describing non-monotonic
      concentration-response relationships were evaluated and one was found to
      consistently provide more accurate estimates of the median and 10% effect
      concentrations compared with a sigmoidal concentration-response model. Predictive
      modeling of the effects of binary mixtures of FL, PPN, and DCF was undertaken
      using an implementation of the concentration addition (CA) conceptual model
      incorporating non-monotonic concentration-response relationships. The
      cytotoxicity of the all three binary combinations could be adequately predicted
      using CA, suggesting that the toxic mode of action in RTG-2 cells is unrelated to
      the therapeutic mode of action of these compounds. The approach presented here is
      widely applicable to the study of mixture toxicity in cases where non-monotonic
      concentration-response relationships are observed. 

PMID- 24582037
TI  - Cytokine alterations in first-episode schizophrenia patients before and after
      antipsychotic treatment.
AB  - Schizophrenia has been associated with central nervous system and peripheral
      immune system imbalances. However, most studies have not yielded conclusive
      results due to limitations such as small sample size, dissimilarities in the
      clinical status of patients and the high variability of cytokine levels within
      the normal human population. Here, we have attempted to account for these
      limitations by carrying out standardised multiplex immunoassay analyses of 9
      cytokines in serum from 180 antipsychotic-naive first-episode schizophrenia
      patients and 350 matched controls across 5 clinical cohorts. All subjects were
      matched for potential confounding factors including age, gender, smoking and body
      mass index. We found that the levels of interleukin (IL)-1RA, IL-10 and IL-15
      were increased significantly in patients across the cohorts. We also found that
      the levels of IL-1RA and IL-10 were decreased in 32 patients who had been
      followed up and treated for 6 weeks with atypical antipsychotics. Interestingly,
      we found that the changes in IL-10 levels were significantly correlated with the
      improvements in negative, general and total symptom scores. These results
      indicate that mixed pro- and anti-inflammatory responses may be altered in first
      onset patients, suggesting a role in the aetiology of schizophrenia. The finding
      that only the anti-inflammatory cytokine IL-10 responded to treatment in parallel
      with symptom improvement suggests that this could be used as a potential
      treatment response biomarker in future studies of schizophrenia.

PMID- 24582038
TI  - Altered autonomic arousal in psychosis: an analysis of vulnerability and
      specificity.
AB  - Vulnerability-stress models implicate that alterations of the autonomous nervous
      system contribute to the development of psychosis. Previous research has found
      autonomic arousal alterations in psychotic disorders and at-risk individuals that
      are not explained by medication alone. To test whether these alterations are
      associated with the extent of an individual's vulnerability and whether they are
      specific to psychosis, we compared participants with psychosis (n=23), first
      degree relatives of individuals with psychosis (n=21), and healthy participants
      with attenuated positive symptoms (n=23) to participants with depression (n=24)
      and healthy controls (n=24). At rest, skin conductance level was assessed and
      photoplethysmography was applied to measure time- and frequency-domain heart rate
      variability (HRV). Univariate and multivariate analyses of covariance with
      perceived stress and psychophysiological values as dependent variables showed
      significant between-group differences for perceived stress (p=.010), heart rate
      (p=.022), time-domain HRV indices (all ps<=.027), and vagal activity (p=.017).
      Group differences in sympathetic activity were nonsignificant (p=.069). In an
      additional analysis with medication as a second between-group factor, the
      physiological between-group differences remained significant or trend significant
      (all ps<=.060). With the exception of sympathetic activity, participants with
      psychosis exhibited more extreme arousal than the control groups. First-degree
      relatives and participants with attenuated symptoms showed comparable autonomic
      activity to healthy controls. Thus, the hypothesized association of an alteration
      of arousal and vulnerability to psychosis was not confirmed. However,
      particularly low time-domain HRV was found for psychosis, with significant
      differences to healthy controls (all ps<=.007) and to depression (all ps<=.004),
      with the latter indicating a specificity to psychosis. 

PMID- 24582040
TI  - All-cause mortality in asymptomatic persons with extensive Agatston scores above
      1000.
AB  - BACKGROUND: Risk assessment in the extensive calcified plaque phenotype has been
      limited by small sample size. OBJECTIVE: We studied all-cause mortality rates
      among asymptomatic patients with markedly elevated Agatston scores > 1000.
      METHODS: We studied a clinical cohort of 44,052 asymptomatic patients referred
      for coronary calcium scans. Mean follow-up was 5.6 years (range, 1-13 years). All
      cause mortality rates were calculated after stratifying by Agatston score (0, 1
      1000, 1001-1500, 1500-2000, and >2000). A multivariable Cox regression model
      adjusting for self-reported traditional risk factors was created to assess the
      relative mortality hazard of Agatston scores 1001 to 1500, 1501 to 2000, and
      >2000. With the use of post-estimation modeling, we assessed for the presence of
      an upper threshold of risk with high Agatston scores. RESULTS: A total of 1593
      patients (4% of total population) had Agatston score > 1000. There was a
      continuous graded decrease in estimated 10-year survival across increasing
      Agatston score, continuing when Agatston score > 1000 (Agatston score 1001-1500,
      78%; Agatston score 1501-2000, 74%; Agatston score > 2000, 51%). After
      multivariable adjustment, Agatston scores 1001 to 1500, 1501 to 2000, and >2000
      were associated with an 8.05-, 7.45-, and 13.26-fold greater mortality risk,
      respectively, than for Agatston score of 0. Compared with Agatston score 1001 to
      1500, Agatston score 1501 to 2000 had a similar all-cause mortality risk, whereas
      Agatston score > 2000 had an increased relative risk (Agatston score 1501-2000:
      hazard ratio [HR], 1.01 [95% CI, 0.67-1.51]; Agatston score > 2000: HR, 1.79 [95%
      CI, 1.30-2.46]). Graphical assessment of the predicted survival model suggests no
      upper threshold for risk associated with calcified plaque in coronary arteries.
      CONCLUSION: Increasing calcified plaque in coronary arteries continues to predict
      a graded decrease in survival among patients with extensive Agatston score > 1000
      with no apparent upper threshold.

PMID- 24582039
TI  - Technical note: Electrocardiogram electrode repositioning for 320-row coronary CT
      angiography in patients with regular and recurrent premature ventricular
      contractions.
AB  - Arrhythmias can compromise image quality and increase radiation exposure during
      coronary CT angiography (CTA). However, premature ventricular contractions (PVCs)
      can occur in a predictable recurrent and regular pattern (ie, bigeminy,
      trigeminy, quadrigeminy) with post-PVC compensatory pauses. Electrocardiographic
      (ECG) electrode repositioning can achieve relative amplification of the R waves
      of PVCs compared with R waves of sinus beats. This technical note describes how
      simple ECG electrode repositioning, combined with an absolute-delay strategy,
      facilitated selective R waves of PVC ECG triggering of image acquisition in 6
      patients with PVC bigeminy or quadrigeminy at the time of 320-row coronary CTA.
      All 6 studies were single heartbeat acquisition scans with excellent image
      quality and a median effective radiation dose of 2.9 mSv (interquartile range,
      2.1-3.8 mSv). Standard ECG electrode positions used for 2 patients with PVC
      bigeminy undergoing coronary CTA were associated with an acquisition over 2
      heartbeats and effective radiation doses of 6.8 and 10.3 mSv, respectively. In
      conclusion, ECG electrode repositioning combined with an absolute-delay strategy
      for regularly recurring PVCs, such as ventricular bigeminy, facilitates high
      image quality and lower radiation dose during coronary CTA. This simple and
      straightforward technique can be considered for all patients with regular and
      recurrent PVCs undergoing coronary CTA. 

PMID- 24582041
TI  - Feasibility of C-arm computed tomography for transcatheter aortic valve
      replacement planning.
AB  - BACKGROUND: The C-arm used for fluoroscopy during transcatheter aortic valve
      replacement (TAVR) may also be used to acquire 3-dimensional data sets similar to
      multidetector row CT (MDCT). OBJECTIVE: The aim of this study was to evaluate the
      feasibility of C-arm CT (CACT) for aortic annulus and root (AoA/R) measurements
      in TAVR planning compared with MDCT. METHODS: Twenty patients who were studied
      for TAVR underwent MDCT and CACT. Two independent observers measured predicted
      perpendicular projection to annular plane, diameters of the aortic annulus, sinus
      of Valsalva, sinotubular junction and ascending aorta, distance of coronary ostia
      to annular plane, sinus of Valsalva height, and leaflet length. Correlation
      between MDCT and CACT and interobserver variability were analyzed. RESULTS: MDCT
      and CACT showed strong correlation for all the measurements of the AoA/R (r
      ranging from 0.62 to 0.94; P between <.001 and .042) and also for the predicted
      perpendicular projection (left/right anterior oblique: r = 0.96, P = .002;
      cranial/caudal: r = 0.83, P = .043). Interobserver variability analysis showed
      disagreement for the measurements of the aortic annulus structures with CACT
      (intraclass correlation coefficient [ICC], <0.25) but not for the rest of the
      variables (ICC between 0.47 and 0.97). MDCT showed no interobserver variability
      for all the measurements (ICC between 0.45 and 0.93). CONCLUSIONS: CACT showed
      strong correlation with MDCT for the measurement of all AoA/R structures.
      However, CACT showed also important interobserver variability for the assessment
      of the aortic annulus. Therefore, valve sizing may not be reliably performed on
      the basis of CACT measurements alone.

PMID- 24582042
TI  - Coronary stent evaluation with coronary computed tomographic angiography:
      comparison between low-osmolar, high-iodine concentration iomeprol-400 and iso
      osmolar, lower-iodine concentration iodixanol-320.
AB  - BACKGROUND: Reliability of coronary angiography by multidetector row CT (MDCT-CA)
      for stent evaluation is still a matter for debate, and it is unknown whether
      contrast medium characteristics may affect diagnostic performance of MDCT-CA.
      OBJECTIVE: We compared iomeprol-400 with iodixanol-320 to evaluate coronary
      stents with MDCT-CA. METHODS: We randomly assigned 254 patients undergoing
      coronary stent follow-up with the use of MDCT-CA to iomeprol-400 at 5.0 mL/sec
      flow rate (group 1; n = 83), iodixanol-320 at 6.2 mL/sec flow rate (group 2; n =
      87), and iodixanol-320 at 5.0 mL/sec flow rate (group 3; n = 84). Heart rate (HR)
      immediately before and at the end of scanning, HR variation, premature heart
      beats, and heat sensation by visual analog scale during scanning were recorded.
      Mean attenuation was measured in the aortic root and coronary arteries. Image
      quality score and type of artifacts were assessed. RESULTS: Mean attenuation was
      significantly lower in group 3 than in the other groups. In group 3, stent
      evaluability was significantly higher and artifact rate was significantly lower
      than in group 2 (99% vs. 91% and 4% vs. 15%) and group 1 (99% vs. 92% and 4% vs.
      17%), respectively, mainly because of a significant lower rate of beam-hardening
      artifacts (3 cases in group 3 vs. 22 and 27 in groups 2 and 3, respectively). In
      group 3, visual analog scale, HR at the end of imaging, and number of patients
      with premature heart beats during the scan were significantly lower than in the
      other groups. CONCLUSIONS: Iodixanol-320 provides better image quality of
      coronary stents, allowing higher MDCT-CA evaluability, than iomeprol-400.

PMID- 24582043
TI  - Effect of the ellipsoid shape of the left ventricular outflow tract on the
      echocardiographic assessment of aortic valve area in aortic stenosis.
AB  - BACKGROUND: Previous studies showed discrepancies between echocardiographic and
      multidector row CT (MDCT) measurements of aortic valve area (AVA). OBJECTIVE: Our
      aim was to evaluate the effect of the ellipsoid shape of the left ventricular
      outflow tract (LVOT), as shown and measured by MDCT, on the assessment of AVA by
      transthoracic echocardiography (TTE) in patients with severe aortic stenosis.
      METHODS: This retrospective single-center study involved 49 patients with severe
      aortic stenosis referred before transcatheter aortic valve implantation. The AVA
      was deduced from the continuity equation on TTE and from planimetry on cardiac
      MDCT. Area of the LVOT was calculated as follows: on TTE, from the measurement of
      LVOT diameter on parasternal long-axis view; on MDCT, from manual planimetry by
      using multiplanar reconstruction perpendicular to LVOT. RESULTS: At baseline,
      correlation of TTE vs MDCT AVA measurements was moderate (R = 0.622; P < .001).
      TTE underestimated AVA compared with MDCT (0.66 +/- 0.15 cm2 vs. 0.87 +/- 0.15
      cm2; P < .001). After correcting the continuity equation with the LVOT area as
      measured by MDCT, mean AVA drawn from TTE did not differ from MDCT (0.86 +/- 0.2
      cm2) and correlation between TTE and MDCT measurements increased (R = 0.704; P <
      .001). CONCLUSION: Assuming that LVOT area is circular with TTE results in
      constant underestimation of the AVA with the continuity equation compared with
      MDCT planimetry. The elliptical not circular shape of LVOT largely explains these
      discrepancies.

PMID- 24582044
TI  - Assessment of isotropic calcium using 0.5-mm reconstructions from 320-row CT data
      sets identifies more patients with non-zero Agatston score and more subclinical
      atherosclerosis than standard 3.0-mm coronary artery calcium scan and CT
      angiography.
AB  - BACKGROUND: The presence of calcified plaque in coronary arteries can be
      quantified by using 0.5-mm isotropic reconstructions from 320-row CT without
      increased radiation dose. Little is known about reclassification of patients with
      non-zero Agatston scores and quantitative measures of calcified plaque using 0.5
      mm reconstructions. OBJECTIVE: The aim was to compare proportions of zero vs. non
      zero Agatston scores (subclinical atherosclerosis) in 0.5-mm isotropic
      reconstructions vs. standard 3.0-mm and CT angiography (CTA) scans on 320-row CT.
      METHODS: Prospectively, we quantified calcified plaque in coronary arteries in
      104 patients by using non-contrast-enhanced scans with 0.5 and 3.0 mm. Coronary
      calcium assessment was determined by 2 observers. Clinically indicated CTA was
      also performed; coronary calcium assessment findings were compared with CTA.
      Ranked Wilcoxon test and chi2 test were performed for comparison. Reproducibility
      for proportion of zero vs non-zero was assessed by kappa statistics. RESULTS:
      Median Agatston score (41.9 [interquartile range (IQR), 3.7-213.6] vs. 5.2 [IQR,
      0.0-128.5]), calcium volume (53.6 mm3 [IQR, 8.1-202.3] vs. 5.1 mm(3) [IQR, 0.0
      96.8],), and lesion number (10.0 [IQR, 3.5-18.5] vs. 1.0 [IQR, 0.0-6.0]) were
      significantly higher on 0.5-mm reconstruction (P < .0001) than on 3.0-mm
      reconstruction. More patients with subclinical atherosclerosis were detected on
      0.5 mm than on 3.0 mm and CTA scans (76.9% vs. 53.8% vs. 54.8%; P < .0001). The
      kappa values for inter-rater agreement were 0.94 and 0.52 on 3.0- and 0.5-mm data
      sets, respectively. However, when Agatston scores < 10 were excluded from
      analysis, the kappa value rose to 0.83. CONCLUSION: Isotropic 0.5-mm
      reconstruction detected 23.1% and 22.1% more patients with subclinical
      atherosclerosis than standard 3.0-mm scans and CTA, which may be more sensitive
      for the detection of subclinical atherosclerosis; its potential clinical utility
      needs to be validated in large, prospective studies.

PMID- 24582045
TI  - Oversizing in transcatheter aortic valve replacement, a commonly used term but a
      poorly understood one: dependency on definition and geometrical measurements.
AB  - BACKGROUND: In transcatheter aortic valve replacement, prosthesis oversizing is
      essential to prevent paravalvular regurgitation. However, the estimated extent of
      oversizing strongly depends on the measurement used for annular sizing. PURPOSE:
      The aim was to investigate the influence of geometrical parameters for
      calculation of relative oversizing in transcatheter aortic valve replacement,
      reported as percentage in relation to the native annulus size, to standardize
      reporting. METHODS: Electrocardiogram-gated cardiac dual-source CT data of 130
      consecutive patients with severe aortic stenosis (mean age, 81 +/- 8 years; 56
      men; mean aortic valve area, 0.67 +/- 0.18 cm2) were included. Aortic annulus
      dimensions were quantified by means of planimetry that yielded area and perimeter
      at the level of the basal attachment points of the aortic cusps during systole.
      Area- and perimeter-derived diameters were calculated as DA = 2 * ?(A/pi) and DP
      = P/pi. Hypothetical prosthesis sizing was based on DA (23-mm prosthesis for 19
      22 mm; 26-mm prosthesis for 22-25 mm; 29-mm prosthesis for 25-28 mm). Relative
      oversizing for hypothetical prosthesis selection was calculated as percentage in
      relation to the native annulus size. RESULTS: Mean annulus area was 492.12 +/-
      94.9 mm2 and mean perimeter was 80.1 +/- 7.6 mm. DP was significantly larger than
      DA (25.5 +/- 2.4 mm vs 24.9 +/- 2.4 mm; P < .001). Mean maximum diameter was 28.1
      +/- 3.0 mm and mean minimal diameter was 22.8 +/- 2.4 mm. Calculated eccentricity
      index [EI = 1 - minimal diameter/maximum diameter)] was 0.19 +/- 0.06. Difference
      between DP and DA correlated significantly with EI (r = 0.67; P < .001). Relative
      oversizing was 10.2% +/- 3.8% and 21.6% +/- 8.4% by DA and area, and 7.8% +/-
      3.9% by both DP and perimeter. CONCLUSION: For planimetric assessment of aortic
      annulus dimensions with CT, the percentage oversizing calculated strongly depends
      on the geometrical variable used for quantifying annular dimensions. Standardized
      nomenclature seems warranted for comparison of future studies.

PMID- 24582046
TI  - Comparison of different strategies of ivabradine premedication for heart rate
      reduction before coronary computed tomography angiography.
AB  - OBJECTIVE: The aim of this study was to assess the effectiveness and safety of
      different strategies of ivabradine therapy by comparing the effects on heart rate
      (HR), blood pressure (BP), and image quality of coronary CT angiography (CTA).
      METHODS: A total of 192 consecutive patients were randomly assigned to 3 groups
      of oral premedication with ivabradine 15 mg (single dose), 10 mg (single dose),
      and 5 mg twice daily for 5 days, prospectively. Patients using HR-lowering drugs
      and patients with beta-blockade contraindication were excluded. The target HR was
      65 beats/min. In addition 5 to 10 mg of intravenous metoprolol was administered
      to the patients at the CT unit, if required. The systolic and diastolic blood BP
      values and the HRs were recorded. Image quality was assessed for 8 of 15 coronary
      segments with a 4-point grading scale. Results were compared with the Kruskal
      Wallis test, one-way ANOVA, and chi2 test. RESULTS: Reductions in mean HR after
      the treatment were 18 +/- 6, 14 +/- 4, and 17 +/- 7 beats/min for groups 1, 2,
      and 3, respectively. With the total additional therapies, 81.3%, 67.2%, and 84.3%
      of the patients achieved HR < 65 beats/min in groups 1, 2, and 3, respectively.
      The mean BP values before coronary CTA were not significantly changed except for
      patients in group 2. Unacceptable (score 0) image quality was obtained in only
      4.5%, 10.2%, and 4.2% of all the coronary segments, in groups 1, 2, and 3,
      respectively. CONCLUSIONS: Our study indicates that coronary CTA with
      premedication with oral ivabradine in all 3 strategies is safe and effective in
      reducing HR, in particular with a beta-blockade combination. All 3 ivabradine
      regimes may be an alternative strategy for HR lowering in patients undergoing
      coronary CTA. Ivabradine 15 mg (single dose) and ivabradine 5 mg twice daily for
      5 days are superior to the ivabradine 10-mg single-dose regime for HR lowering
      without adjunctive intravenous beta-blocker usage.

PMID- 24582047
TI  - Demonstration of doubly committed juxta-arterial ventricular septal defect with
      aortic valve prolapse by cardiac computed tomography.
AB  - A 24-year-old man presented to our hospital with symptoms of dyspnea and
      palpitation for 2 weeks. Cardiac CT showed not only a leaflet coaptation defect
      in the aortic valve but also a small ventricular septal defect (VSD) immediately
      beneath the prolapsed right coronary cusp. A shunt flow in the direction of the
      right ventricular outflow tract though the defect indicated the doubly committed
      juxta-arterial type of VSD. A doubly committed juxta-arterial VSD of 3 mm was
      confirmed and repaired via pulmonary arteriotomy. 

PMID- 24582048
TI  - Right coronary artery aneurysm with aneurysmal dilation and thrombosis of the
      sinoatrial nodal branch mimicking a right atrial mass.
AB  - Aneurysms of the branches of the coronary arteries are rare. We report a case of
      a right coronary artery aneurysm with aneurysmal dilation and thrombosis of the
      sinoatrial nodal branch presenting as a right atrial mass. The patient underwent
      multiple imaging evaluations before coronary CT angiography diagnosed aneurysm
      and thrombosis of the sinoatrial nodal branch. 

PMID- 24582049
TI  - Prospective assessment of the CryoMaze procedure with continuous outpatient
      telemetry in 136 patients.
AB  - BACKGROUND: Only 40% of patients with atrial fibrillation (AF) undergoing cardiac
      surgery are treated with surgical AF correction. We prospectively studied
      endocardial cryoablation of the Cox-maze III lesion set following prespecified
      rhythm assessment with outpatient telemetry. METHODS: Between 2007 and 2011, 136
      patients underwent surgical AF correction using an argon-powered cryoablation
      device. Patients wore continuous electrocardiogram monitoring prior to and at 6,
      12, and 24 months after surgery. The average length of monitoring was 6.5+/-1
      days prior to surgery and 11+/-4 days at each time point after surgery. Patients
      were assessed for cardiac rhythm, interval cardioversion or ablation procedures,
      pacemaker placement, and the use of warfarin or antiarrhythmic medications. The
      primary endpoint of this study was freedom from AF at 1 year. RESULTS: Mean
      patient age was 66+/-12 years, 50% (69 of 138) were male and 41% (55 of 134) had
      persistent AF. CryoMaze was done in conjunction with mitral valve operation in
      95% (131 of 138) and other procedures in 41% (56 of 138). Follow-up was 96%
      complete at 1 year and 90% at 2 years. Freedom from AF was 76% at 1 year.
      Perioperative mortality and stroke rates were both 1.5% (2 of 138). Perioperative
      pacemaker implantation was required in 7% (9 of 136). In univariate analysis,
      younger age, female gender, decreased height and weight, smaller preoperative and
      postoperative left atrial diameter, intermittent AF, and freedom from AF at
      discharge were associated with freedom from AF at 1 year. Actuarial 2- and 4-year
      (Kaplan-Meier) survival were 93% and 80%, respectively. CONCLUSIONS: The CryoMaze
      procedure is safe and is associated with 76% freedom from AF at 1 year.

PMID- 24582050
TI  - The correction index: setting the standard for recommending operative repair of
      pectus excavatum.
AB  - BACKGROUND: The Haller index, derived from a chest computed tomography scan,
      remains the standard for determining candidacy for pectus excavatum repair
      (Haller index>=3.25). However, it has been suggested that this index may not
      accurately reflect pectus severity in patients with abnormal chest wall
      morphologies. This study explores a new, more appropriate criteria for
      recommending repair based on a correction index, while still incorporating the
      standard set by the Haller index. METHODS: A database of 75 patients with pectus
      excavatum who received computed tomography scans was compiled. For each patient,
      a staff radiologist calculated the Haller index, a correction index, and an ideal
      chest index from the computed tomography image with the greatest sternal
      depression. A correlation was assessed between all Haller and correction indices
      and separately for those with standard and nonstandard chest dimensions as
      assessed by an ideal chest index. RESULTS: There was a modest correlation between
      the Haller and correction indices measured in this cohort (r=0.79; p<0.0001).
      When patients with aberrant ideal chest dimensions were removed from analysis,
      Haller and correction indices showed a stronger correlation (r=0.86; p<0.0001).
      CONCLUSIONS: The correction index provides an accurate assessment of pectus
      severity, and by the nature of the measurement, reflects the potential degree of
      operative repair. The Haller index correlates well with the correction index in
      pectus patients with standard chest wall dimensions, but is quite discrepant in
      the nonstandard chest. We recommend operative repair for pectus excavatum with a
      correction index of 28% or more, because this value correlates with the long
      accepted standard (Haller index>=3.25) and this index remains accurate even in
      nonstandard chest morphologies.

PMID- 24582051
TI  - Treating locally advanced disease: an analysis of very large, hilar lymph node
      positive non-small cell lung cancer using the National Cancer Data Base.
AB  - BACKGROUND: Very large, locally advanced non-small cell lung cancers (NSCLC)
      remain a therapeutic challenge. This retrospective study compares the effect of
      treatment modalities on survival of patients with large NSCLC with hilar lymph
      node involvement (T3>7 cmN1). METHODS: The National Cancer Data Base was used to
      identify adult patients who were diagnosed with T3>7 cmN1 NSCLC from 1999 to 2005
      (n=642). Nonsurgical treatments included chemoradiation, chemotherapy, radiation
      therapy, or no treatment, whereas primary surgical treatments included surgery,
      chemoradiation or chemotherapy prior to surgery, chemoradiation or chemotherapy
      after surgery, or postoperative radiotherapy. Five-year overall survival (OS) was
      estimated by the Kaplan-Meier method and comparisons made using log-rank tests
      and Cox regression models. RESULTS: A total of 642 patients were evaluated; 425
      nonsurgical (66%) and 217 surgical (34%). Primary surgical therapy was associated
      with improved 5-year OS; 28% versus 8% and 4% for nonsurgical and no treatment,
      respectively (p<0.001). The 5-year OS were 11%, 5%, 2%, and 4% for
      chemoradiation, chemotherapy, radiation therapy, and no treatment, respectively
      (p<0.001). The 5-year OS were 16% for surgery only, 40% and 44% for neoadjuvant
      chemoradiation or chemotherapy with surgery, respectively, 40% and 38% for
      adjuvant chemoradiation or chemotherapy with surgery, respectively, and 18% for
      postoperative radiotherapy (p<0.001). On multivariate analysis, surgery and
      chemotherapy in most combinations were associated with significantly improved OS
      compared with chemoradiation only. CONCLUSIONS: Surgery with systemic therapy
      delivered in a neoadjuvant or adjuvant fashion for patients with T3>7 cmN1 NSCLCs
      is associated with improvements in OS.

PMID- 24582052
TI  - Long-term survival of patients with pN2 lung cancer according to the pattern of
      lymphatic spread.
AB  - BACKGROUND: N2 involvement has dramatic consequences on the prognosis and
      management of patients with non-small cell lung cancer (NSCLC). N2-NSCLC may
      present with or without N1 involvement, constituting non-skip (pN1N2) and skip
      (pN0N2) diseases, respectively. As the prognostic impact of this
      subclassification is still a matter of debate, we analyzed the prognosis of pN2
      patients according to the pN1-involvement and the number of N2-stations
      concerned. METHODS: The medical records of consecutive patients who underwent
      surgery for pN2-NSCLC in 2 French centers between 1980 and 2009 were
      prospectively collected and retrospectively reviewed. Patients undergoing
      induction therapy, exploratory thoracotomy, incomplete mediastinal
      lymphadenectomy, or incomplete resections were excluded. The prognoses of pN1N2
      and pN0N2 patients were first compared, and then deciphered according to the
      number of N2 stations involved (single-station: 1S, multi-station: 2S). RESULTS:
      All together, 871 patients underwent first-line complete surgical resection for
      pN2-NSCLC during the study period, including 258 pN0N2 (29.6%) and 613 pN1N2
      (70.4%) patients. Mean follow-up was 72.8+/-48 months. Median, 5- and 10-year
      survivals were, respectively, 30 months, 34%, and 24% for pN0N2 and 20 months,
      21%, and 14% for pN1N2 patients (p<0.001). Multivariate analysis revealed 3
      different prognostic groups; ie, favorable in pN0N2-1S disease, intermediate in
      pN0N2-2S and pN1N2-1S diseases, and poor in pN1N2-2S disease (p<0.001).
      CONCLUSIONS: Among pN2 patients, the combination of N1 involvement (pN0N2 vs
      pN1N2) and number of involved N2 stations (1S vs 2S) are independent prognostic
      factors. These results might be taken into consideration to sub-classify the
      heterogeneous pN2-NSCLC group of patients.

PMID- 24582053
TI  - Reduction of tunnel enlargement with use of autologous ruptured tissue in
      anterior cruciate ligament reconstruction: a pilot clinical trial.
AB  - PURPOSE: To compare the tunnel enlargement of double-bundle (DB) anterior
      cruciate ligament reconstruction (ACLR) with and without suturing of autologous
      ruptured tissue to hamstring graft in patients with subacute anterior cruciate
      ligament injury. METHODS: Ten patients with subacute (<=3 months after injury)
      anterior cruciate ligament rupture were randomly allocated to undergo DB ACLR
      with suturing of the ruptured tissue to hamstring graft (n = 5) or conventional
      DB ACLR (n = 5). When autologous ruptured tissue was used, remnant ruptured
      tissue was then harvested, divided into 4 pieces, placed between the loops at the
      distal and proximal portions of the graft, and secured with the suture. As the
      primary endpoint, tunnel volume assessment by 3-dimensional multi-detector row
      computed tomography (MDCT) was performed 1 year after ACLR. To assess the
      efficacy of these procedures, the Lysholm score, anterior tibial translation
      (measured with a KT-1000 arthrometer [MEDmetric, San Diego, CA]), and rotational
      instability (measured by the pivot-shift test) were evaluated after 2 years.
      RESULTS: Tunnel volume enlargement between 3 weeks and 1 year after ACLR as
      assessed by 3-dimensional MDCT was significantly less for ACLR using ruptured
      tissue than for conventional ACLR, especially at the femoral site (P < .05).
      However, the postoperative Lysholm score, anterior stability of the knee measured
      with the KT-1000 arthrometer, and rate of negative manual pivot-shift test
      results did not differ significantly between the 2 groups. There was no
      correlation to the clinical outcomes in terms of tunnel size. CONCLUSIONS: The
      Lysholm score, anterior laxity measured with the KT-1000 arthrometer, and
      rotational instability according to the pivot-shift test did not differ
      significantly between ACLR using ruptured tissue and the conventional technique.
      However, ACLR using ruptured tissue produced less femoral tunnel enlargement as
      assessed by MDCT, warranting further long-term follow-up to elucidate its
      effectiveness. LEVEL OF EVIDENCE: Level II, prospective comparative study.

PMID- 24582054
TI  - Commentary for JCF review "Drug induced complications; can we do more?" J Cyst
      Fibros 2013 Dec;12(6):547-58.

PMID- 24582055
TI  - Platelet activation by riboflavin and UV light: is it really the other side of
      the coin?
AB  - INTRODUCTION: Nowadays transfusion safety is still put at risk by contamination
      of pathogens. The Mirasol PRT System blocks the replication of pathogens and
      white blood cells. Our goal was to quantify the activation of platelets after
      treatment with the Mirasol device. MATERIALS AND METHODS: From September to
      December 2013, 131 platelet collections were studied using a simple flow
      cytometric strategy. RESULTS: There was a significant correlation between the
      percentage of platelet activated before and after the treatment. CONCLUSION: Our
      results induced us to think that the activation of platelets after treatment was
      acceptable.

PMID- 24582056
TI  - DAT positivity in blood donors: a perplexing scenario.
AB  - A blood request was received for 70 year male patient suffering from Chronic
      Obstructive Pulmonary Disease with anemia. One unit was found incompatible in AHG
      phase. Patient's antibody screen, indirect antiglobulin test (IAT), direct
      antiglobulin test (DAT) and auto control was negative. DAT of donor unit was
      positive with anti IgG gel card and negative with C3d reagent along with positive
      auto control. Donor was 30 year male with no history of blood transfusion and
      medication and had no evidence of hemolysis. Donors with positive DAT should be
      deferred, notified and referred to physician but further studies are required.

PMID- 24582057
TI  - Acknowledgment and gratitude for Professor Alvin Fox (Editor-in-Chief, 1996
      2013).

PMID- 24582060
TI  - The basement membrane of the isolated rat colonic mucosa. A light, electron and
      atomic force microscopy study.
AB  - Basement membranes (BM) are structures of the extracellular matrix (ECM), which
      are involved in epithelial barriers, but also play an important role in processes
      such as cell adhesion, cell growth and tissue healing. The aim of this study was
      to investigate possible effects of cell removal on the structure of the BM of the
      colonic mucosa. The superficial epithelium was removed with EDTA and the samples
      were then mechanically fixed for immunohistochemistry, TEM, SEM and AFM. For SEM
      and AFM, some samples were also prepared according to the OTO method. BM marker
      proteins were detected after cell removal by immunohistochemistry, indicating
      that BM remains. However, a lamina lucida (LL) was no longer visible in TEM, it
      disappeared and the BM became slightly thinner. The surface topography of the BM
      is characterized by the presence of globules, fenestrations and pore-like
      structures, which were visualized with SEM and AFM. Noteworthy is the
      visualization for the first time with AFM of a 3D network of fine fibers and
      filaments ("cords"), which very much resembled that described with TEM by Inoue
      (1994). An unresolved question is whether the pore-like structures observed in
      this study, especially with SEM, actually correspond to the pores of the BM whose
      existence has been demonstrated functionally. In conclusion, the structural
      patterns and changes described could be considered as a reference to evaluate the
      effects of other decellularization protocols on BMs, such as those used in tissue
      engineering.

PMID- 24582061
TI  - Randomized clinical trial of the effects of a combination of acepromazine with
      morphine and midazolam on sedation, cardiovascular variables and the propofol
      dose requirements for induction of anesthesia in dogs.
AB  - The present study evaluated the effects of acepromazine combined with midazolam
      and morphine on sedation and cardiovascular variables as well as the propofol
      dose required for induction of anesthesia in dogs compared with acepromazine
      morphine or midazolam-morphine. Dogs were randomly assigned to receive an
      intramuscular administration of (1) acepromazine (0.05 mg/kg) with 0.5mg/kg of
      morphine (group AM, n=10), (2) midazolam (0.5mg/kg) with 0.5mg/kg of morphine
      (group MM, n=9), or (3) acepromazine with midazolam and morphine at the same
      doses (group AMM, n=10). After 30 min, sedation was assessed by a numeric
      descriptive scale (NDS, range 0-3) and a simple numerical scale (SNS, range 0
      10). Dogs were then administered IV propofol to allow endotracheal intubation.
      NDS and SNS scores were significantly higher in the AMM than in the MM group
      (P<0.05). There was a trend towards more dogs presenting with intense sedation
      (NDS=3) in AMM (6/10 dogs) compared with AM (1/10 dogs) and MM (1/9 dogs)
      (P=0.057). The propofol dose required for induction of anesthesia was
      significantly lower in AMM (4.0mg/kg) compared with MM (6.0mg/kg, P<0.01) but not
      AM (4.6 mg/kg). Heart rate decreased in AM after treatment and after intubation.
      Blood pressure decreased in groups AM and AMM following treatment and in all
      groups after intubation. The combination AMM resulted in intense sedation more
      frequently than AM and MM, and provided the greatest sparing effect in the
      propofol dose. Administration of AM and AMM but not MM decreased blood pressure
      although hypotension was not recorded in healthy dogs.

PMID- 24582062
TI  - A role of placental growth factor in hair growth.
AB  - BACKGROUND: The dermal papilla (DP) comprises specialized mesenchymal cells at
      the bottom of the hair follicle and plays a pivotal role in hair formation,
      anagen induction and the hair cycle. In this study, DPs were isolated from human
      hair follicles and serially subcultured. From each subculture at passages 1, 3,
      and 5 (n=4), we compared gene expression profiles using mRNA sequencing. Among
      the growth factors that were down-regulated in later passages of human DP cells
      (hDPCs), placental growth factor (PlGF) was selected. OBJECTIVE: To elucidate the
      effect of PlGF on hair growth. METHODS: We evaluated the effect of PlGF on hDPCs
      and on ex vivo hair organ culture. We investigated the effect of PlGF on an in
      vivo model of depilation-induced hair regeneration. RESULTS: We confirmed that
      the mRNA and protein expression levels of PlGF significantly decreased following
      subculture of the cells. It was shown that PlGF enhanced hair shaft elongation in
      ex vivo hair organ culture. Furthermore, PlGF significantly accelerated hair
      follicle growth and markedly prolonged anagen hair growth in an in vivo model of
      depilation-induced hair regeneration. PlGF prevented cell death by increasing the
      levels of phosphorylated extracellular signal-regulated kinase (ERK) and cyclin
      D1 and promoted survival by up-regulation of phosphorylated Akt and Bcl2, as
      determined by Western blotting. CONCLUSION: Our results suggest that PlGF plays a
      role in the promotion of hair growth and therefore may serve as an additional
      therapeutic target for the treatment of alopecia.

PMID- 24582064
TI  - Activation of mitosis and angiogenesis in diabetes-impaired wound healing by
      processed human amniotic fluid.
AB  - BACKGROUND: Functional characterization of human amniotic fluid (AF) proteome,
      845 proteins, has revealed that top three functions are cell proliferation,
      movement and differentiation, events fundamental to development, and tissue
      repair. Although these findings fortify the idea that AF components play roles in
      regeneration-like fetal wound healing, it is not known whether the components
      endure processing. Therefore, we processed AF and tested its effects on diabetes
      impaired wound healing in an animal model. MATERIALS AND METHODS: Through a
      germfree procedure, mature and premature AF samples were collected, respectively,
      from the mothers of full-term and preterm infants. Excisional wounds were
      generated on the dorsum of diabetic rats. Wounds were treated on day 3 and
      harvested on day 7 postwounding. Proliferating cell nuclear antigen and alpha
      smooth muscles actin, markers for mitosis and angiogenesis, respectively, were
      assessed by in situ immunodetection method. RESULTS: Significant increases in the
      rate of wound closure and proliferating cell nuclear antigen-expressing cells
      were observed in AF-treated wounds when compared with that of sham and control
      wounds. Likewise, the number of large vessels was significantly increased in the
      wounds treated with the AF. However, population of myofibroblasts was not
      affected by the treatment. The mature and premature AF were almost equally
      effective. CONCLUSIONS: Our data, for the first time, show that processed AF
      accelerates diabetes-impaired wound healing by activating mitosis and
      angiogenesis, indicating that bioactive molecules in AF may endure processing. We
      believe that processed forms of this naturally designed "Cocktail" of bioactive
      molecules may have multiple clinical applications.

PMID- 24582065
TI  - Dexamethasone effects on vascular flow and organ injury in septic mice.
AB  - BACKGROUND: To demonstrate the effects of low-dose dexamethasone treatment on
      mesenteric artery blood flow, oxidative injury, vascular reactivity, and survival
      in Swiss albino mice with intra-abdominal polymicrobial sepsis accomplished by
      cecal ligation and puncture (CLP). METHODS: Mice were allocated to CLP + saline,
      CLP + dexamethasone, sham + saline, and sham + dexamethasone subgroups to
      evaluate blood flow, organ injury, and vascular response to consecutive
      phenylephrine administrations at 24, 48, and 72 h. Survival rates were also
      evaluated in a different group of mice. Dexamethasone (1 mg/kg/d) and saline (4
      mL/kg/d) were administered intraperitoneally to mice 2 h after CLP or sham
      procedure, whichever appropriate, and repeated once a day until evaluation time
      at 48 and 72 h. Relaparotomy was performed at the concerned time and mesenteric
      blood flow was measured, and liver, lung, and peritoneum samples were obtained.
      Alteration in mesenteric blood flow response to intravenous phenylephrine
      injections was recorded at the related time intervals in different mice groups.
      Survival group was followed up by 7-d administration of dexamethasone or saline
      for 18 d. RESULTS: The significant fall in mesenteric blood flow after CLP
      ameliorated with dexamethasone treatment at 48 and 72 h. Dexamethasone also
      diminished the malonyl dialdehyde level, which is an indicator of organ injury
      raised after CLP, at 24 h in liver, lung, and peritoneum samples. Dexamethasone
      therapy has significantly enhanced the vascular response to phenylephrine
      injections at all doses; however, no change was observed in survival rates.
      CONCLUSIONS: Low-dose dexamethasone has beneficial effects on mesenteric blood
      flow and organ injury in experimental sepsis models.

PMID- 24582066
TI  - Effects of terlipressin on microcirculation of small bowel mesentery in rats with
      endotoxic shock.
AB  - BACKGROUND: Septic shock is still related to unacceptably high morbidity and
      mortality. Microcirculatory alteration has been demonstrated to be one important
      reason associated with this evolution. Vasoactive drugs are often used to restore
      adequate arterial pressure and tissue perfusion in septic shock. To define the
      roles of different drugs, the effects of terlipressin (TP) on the
      microcirculation of small bowel mesentery in rats with endotoxic shock were
      evaluated and compared with those of norepinephrine (NE). METHODS: Twenty-five
      adult male Wistar rats were randomized to the control (n = 5), TP (n = 10), and
      NE (n = 10) groups. After endotoxic shock was induced by intravenous
      lipopolysaccharide administration for 30 min, rats in the NE and TP groups were
      infused with saline 5 mL/kg/h and simultaneously given NE 4 MUg/kg/min or TP 8
      MUg/kg/h. The mean arterial pressure, heart rate, blood gas analysis, and
      microvascular blood flow images of small bowel mesentery were recorded. RESULTS:
      After fluid resuscitation and vasopressor infusion, the mean arterial pressure
      was restored to the baseline values in the NE and TP groups. In the TP group, the
      heart rate was significantly lower compared with the NE group (P = 0.013). The
      proportion of perfused vessels and the microvascular flow index (MFI) were
      significantly increased; furthermore, the heterogeneity index of small vessels
      was markedly decreased in both the interventional groups with respect to the
      control group. Compared with the NE group, the MFI was significantly higher (P <
      0.05) and the heterogeneity index was significantly lower (P < 0.05) in the TP
      group. CONCLUSIONS: Both TP and NE improved hemodynamic and microcirculatory
      alterations in rats with endotoxic shock. Compared with NE, TP was more effective
      in promoting MFI and improving the heterogeneity of small bowel mesentery in
      rats.

PMID- 24582063
TI  - Vein graft adaptation and fistula maturation in the arterial environment.
AB  - Veins are exposed to the arterial environment during two common surgical
      procedures, creation of vein grafts and arteriovenous fistulae (AVF). In both
      cases, veins adapt to the arterial environment that is characterized by different
      hemodynamic conditions and increased oxygen tension compared with the venous
      environment. Successful venous adaptation to the arterial environment is critical
      for long-term success of the vein graft or AVF and, in both cases, is generally
      characterized by venous dilation and wall thickening. However, AVF are exposed to
      a high flow, high shear stress, low-pressure arterial environment and adapt
      mainly via outward dilation with less intimal thickening. Vein grafts are exposed
      to a moderate flow, moderate shear stress, high-pressure arterial environment and
      adapt mainly via increased wall thickening with less outward dilation. We review
      the data that describe these differences, as well as the underlying molecular
      mechanisms that mediate these processes. Despite extensive research, there are
      few differences in the molecular pathways that regulate cell proliferation and
      migration or matrix synthesis, secretion, or degradation currently identified
      between vein graft adaptation and AVF maturation that account for the different
      types of venous adaptation to arterial environments. 

PMID- 24582067
TI  - T-cell activation Rho GTPase-activating protein expression varies with
      inflammation location and severity in Crohn's disease.
AB  - BACKGROUND: The T-cell activation Rho GTPase-activating protein (TAGAP) gene has
      a regulatory role in T cell activation. We have previously suggested a
      correlation between the TAGAP-associated single nucleotide polymorphism rs212388
      and protection from anal sepsis in Crohn's disease (CD) patients. The present
      study sought to evaluate TAGAP's expression in colonic tissue of CD patients with
      varying disease severity and location. MATERIALS AND METHODS: Five transverse, 17
      left, and five sigmoid colectomy specimens from 27 CD patients with varying
      disease severity (16 male, mean age at diagnosis 26.4 +/- 2.2 y) were evaluated
      for TAGAP messenger RNA expression. Fisher exact, Mann-Whitney, and Welch two
      sample t-tests were used for statistical evaluation. Immunohistochemistry
      confirmed results. RESULTS: Patients with tissue demonstrating lower TAGAP
      messenger RNA expression (less than the overall mean) were younger at diagnosis
      (mean age 21.1 +/- 6.3 versus 32.5 +/- 13 y, P = 0.009). Increased TAGAP
      expression was seen in moderate or severely diseased tissue versus tissue with no
      or mild disease (RQ = 1.3 +/- 0.34 versus 0.53 +/- 0.09, P = 0.050). This was the
      most dramatic in the sigmoid colon (P = 0.041). TAGAP expression was increased in
      more distal tissue with a significant difference seen when comparing transverse
      versus sigmoid colon with moderate or severe disease (0.51 +/- 0.14 versus 1.9 +/
      0.37, P = 0.049). CONCLUSIONS: Colonic expression of TAGAP in CD patients varied
      according to disease severity and location, being the most elevated in patients
      with severe disease in the sigmoid colon. Whether changes in TAGAP expression are
      a result of disease response or inherent to the disease pathophysiology itself
      remains to be determined. This gene warrants further investigation for its role
      in CD.

PMID- 24582068
TI  - Mortality after trauma laparotomy in geriatric patients.
AB  - BACKGROUND: Geriatric patients are at higher risk for adverse outcomes after
      injury because of their altered physiological reserve. Mortality after trauma
      laparotomy remains high; however, outcomes in geriatric patients after trauma
      laparotomy have not been well established. The aim of our study was to identify
      factors predicting mortality in geriatric trauma patients undergoing laparotomy.
      METHODS: A retrospective study was performed of all trauma patients undergoing a
      laparotomy at our level 1 trauma center over a 6-y period (2006-2012). Patients
      with age >=55 y who underwent a trauma laparotomy were included. Patients with
      head abbreviated injury scale (AIS) score >= 3 or thorax AIS >= 3 were excluded.
      Our primary outcome measure was mortality. Significant factors in univariate
      regression model were used in multivariate regression analysis to evaluate the
      factors predicting mortality. RESULTS: A total of 1150 patients underwent a
      trauma laparotomy. Of which 90 patients met inclusion criteria. The mean age was
      67 +/- 10 y, 63% were male, and median abdominal AIS was 3 (2-4). Overall
      mortality rate was 23.3% (21/90) and progressively increased with age (P =
      0.013). Age (P = 0.02) and lactate (P = 0.02) were the independent predictors of
      mortality in geriatric patients undergoing laparotomy. CONCLUSIONS: Mortality
      rate after trauma laparotomy increases with increasing age. Age and admission
      lactate were the predictors of mortality in geriatric population undergoing
      trauma laparotomies.

PMID- 24582069
TI  - Effect of cold perfusion and perfluorocarbons on liver graft ischemia in a
      donation after cardiac death model.
AB  - BACKGROUND: Effects of two perfluorocarbon (PFC) formulations (perfluorodecalin
      emulsion and perfluorodecalin liquid) on the quality of liver graft preservation,
      in a donation after cardiac death (DCD) rat model, were investigated. The
      significance of continuous graft perfusion during cold preservation was also
      explored. MATERIALS AND METHODS: DCD model: 30 min after cardiopulmonary arrest
      was initiated, livers were excised and flushed with cold University of Wisconsin
      (UW) solution (+/- PFC) and preserved in the same solution for 8 h. The study
      groups were preserved as follows: group 1: no perfusion; group 2: perfusion with
      UW; group 3: PFC was administered before cardiac arrest and the liver was
      perfused with UW alone; and groups 4 and 5: perfused with UW + 1 of two PFCs. In
      a baseline group used only for comparison of gene expression, livers were quick
      frozen after cardiac arrest. Microarrays were used to analyze liver messenger RNA
      transcripts. Histopathologic, immunohistochemical, and ADP/ATP ratio evaluations
      were performed to assess the quality of graft preservation. RESULTS: Significant
      decreases in downregulation and increases in upregulation of hepatic genes
      (relative to baseline) were demonstrated in all perfusion groups. This trend was
      most pronounced in the PFC groups. Lower fat content and ADP/ATP ratio and a
      reduction in Caspase 3 activation were found in all perfusion groups. CONCLUSION:
      Hypothermic perfusion of rat DCD liver grafts with oxygenated UW solution (+/-
      PFC) produced superior preservation compared with nonperfusion storage. The
      observed changes in expression of hepatic genes may represent a protective effect
      in the DCD model.

PMID- 24582070
TI  - The effects of iloprost on colonic anastomotic healing in rats under obstructive
      ileus conditions.
AB  - BACKGROUND: The aim of this study was to investigate the effects of iloprost, on
      colonic anastomotic healing in rats, under obstructive ileus conditions.
      MATERIALS AND METHODS: Eighty male Albino rats were randomized into four groups
      of 20 animals each. They underwent colonic resection followed by an inverted
      anastomosis. The rats of group 1 (control) and group 2 (ileus) received 3 mL of
      saline 0.9% intraperitoneally and those of group 3 (iloprost), and group 4 (ileus
      + iloprost) iloprost (2 MUg/kg of body weight), immediately postoperatively and
      daily until the day of sacrifice. Each group was further divided into two equal
      subgroups, depending on the day of sacrifice. The animals of subgroup "a" were
      sacrificed on the fourth postoperative day, whereas those of "b" on the eighth
      day. Macroscopic and histologic assessment was performed, whereas anastomotic
      bursting pressures and the tissue concentrations in hydroxyproline and
      collagenase I were evaluated. RESULTS: Means of bursting pressure,
      neoangiogenesis, fibroblast activity, and hydroxyproline concentration were
      significantly increased in group 4 compared with group 2. In addition, on the
      fourth postoperative day, the inflammatory cell infiltration and the collagenase
      I concentration were significantly decreased in group 4 compared with group 2.
      Moreover, on the eighth postoperative day, collagen deposition was significantly
      increased in group 4 compared with group 2. CONCLUSIONS: Iloprost after
      intraperitoneal administration reverses the negative effect of obstructive ileus.
      It promotes not only the angiogenic activity but also collagen formation,
      resulting in increased bursting pressures on the fourth and eighth postoperative
      days.

PMID- 24582071
TI  - Evaluation of a mobile electronic assistant to aid in fluindione prescription:
      the INRPlus cluster randomized trial.
AB  - INTRODUCTION: Regular monitoring of the international normalized ratio (INR) is
      crucial for dose adjustment of vitamin K antagonists (VKA) to maximize time in
      therapeutic range (TTR). We compared the use of a mobile electronic assistant
      INRPlus which proposes patient-specific fluindione doses, to standard fluindione
      management in a cluster randomized controlled study. PATIENTS AND METHODS: Twenty
      clusters of six general practitioners were randomized to adjust fluindione doses
      in VKA-treated patients either using INRPlus or according to routine practice.
      TTR was measured over 6 months, along with time spent above or below the
      recommended INR range, frequency of measurements and related complications.
      RESULTS: Of the 595 included patients, 551 were assessable (259 INRPlus, 292
      control) and had a mean of 1.6 INR measurements/month. TTR was not significantly
      different between the two groups, 72.7% [Q1: 58.1%; Q3: 90%] in INRPlus patients
      and 71.2% [Q1: 54.8%; Q3: 88.2%] in control patients (p=0.445). At least 60% time
      within reference ranges was reported in 73.4% of INRPlus patients and 67.1% of
      control patients (relative risk 1.09, 95%CI 0.98-1.22, p=0.115). No significant
      differences were reported between the two groups for time outside reference
      ranges, frequency of measurements or complications. Eighty-two percent (82%) of
      patients complying with INRPlus-proposed doses spent more than 60% of TTR versus
      66.9% of non-compliant patients and 67.1% of reference patients. CONCLUSIONS: In
      this trial, the use of the INRPlus electronic assistant resulted in a non
      significant improvement in TTR that may be due to a higher than expected TTR in
      the control group.

PMID- 24582072
TI  - Balance and gait adaptations in patients with early knee osteoarthritis.
AB  - Gait adaptations in people with severe knee osteoarthritis (OA) have been well
      documented, with increased knee adduction moments (KAM) the most commonly
      reported parameter. Neuromuscular adaptations have also been reported, including
      reduced postural control. However these adaptations may be the result of
      morphological changes in the joint, rather than the cause. This study aimed to
      determine if people with early OA have altered gait parameters and neuromuscular
      adaptations. Gait and postural tasks were performed by 18 people with early
      medial knee OA and 18 age and gender-matched control subjects. Parameters
      measured were kinematics and kinetics during gait and postural tasks, and centre
      of pressure and electromyographic activity during postural tasks. OA subjects
      showed no differences in the gait parameters measured, however they demonstrated
      postural deficits during one-leg standing on both their affected and unaffected
      sides and altered hip adduction moments compared with controls. Increased
      activity of the gluteus medius of both sides (p<0.05), and quadriceps and
      hamstrings of the affected side (p<0.05) during one-leg standing compared with
      controls were also noted. This study has demonstrated that gait adaptations
      commonly associated with OA do not occur in the early stages, while neuromuscular
      adaptations are evident. These results may be relevant for early interventions to
      delay or prevent osteoarthritis in its early stages.

PMID- 24582073
TI  - Reasons for hospitalization in Parkinson's disease: a case-control study.
AB  - BACKGROUND: To characterize reasons for hospital admission, mortality and
      surgical procedures in patients with Parkinson's disease (PD) compared to
      controls. METHODS: The clinical features of all consecutive patients from 2000 to
      2007 were reviewed. We identified patients with PD (ICD 9 code 332.0) from a
      database of our General Hospital (Vimercate) with a catchment's population of
      180,000. Data on admitting wards as well as reasons for admission, surgical
      procedures performed and clinical outcome were collected. Clinical data were
      compared to an age and sex matched control population admitted in the same period
      of time. RESULTS: The total number of admissions was 367. Mean age was 76.7
      years. The mean duration of stay was 9.2 days for controls and 9.7 for PD
      patients. A comorbid disorder was the cause of admission in 80% of cases and 79%
      of cases came from the Emergency Room. Infectious diseases, mainly respiratory
      infections, were more frequent in PD of both sexes, while trauma was
      significantly higher only in PD men. Percentage of patients treated surgically
      was similar in both cases and controls. Intrahospital mortality was 6% both in PD
      and controls. Infectious diseases were more frequent in PD patients while
      cardiovascular death was more frequent in controls. CONCLUSIONS: Comorbidity in
      PD is higher than reported in other reports. In our study PD patients had the
      same length of hospitalization and intrahospital mortality as controls. The
      presence of a control population allows to discriminate between general
      complications of the elderly and specific vulnerabilities of PD patients.

PMID- 24582074
TI  - STN-DBS does not change emotion recognition in Parkinson's disease.

PMID- 24582075
TI  - Protective effect of trimetazidine on amikacin-induced ototoxicity in rats.
AB  - OBJECTIVE: Aminoglycoside antibiotics are known to have ototoxic effects and may
      induce sensorineural hearing loss. This study investigated the protective effect
      of trimetazidine, which has antioxidant and cytoprotective properties, against
      amikacin ototoxicity. METHODS: Thirty-two male rats were divided into four groups
      - amikacin, amikacin + trimetazidine, trimetazidine, and control groups.
      Trimetazidine, 10 mg/kg per day, was given for 14 days by oral gavage. Amikacin,
      600 mg/kg per day, was also given for 14 days, by the intramuscular route.
      Distortion product otoacoustic emission (DPOAE) and auditory brainstem response
      (ABR) tests were applied to the rats for hearing assessment. At the termination
      of the study, the biochemical parameters were calculated to evaluate the
      oxidative status. RESULTS: The DPOAE values of the amikacin group were
      significantly lower on the 7th and 14th days than those of the trimetazidine +
      amikacin group and there was an increase in the ABR thresholds. The ABR
      thresholds for the amikacin group on the 7th and 14th days were significantly
      higher than the levels on the first day of the study, while there was no
      significant increase in those values in the trimetazidine + amikacin group. The
      total oxidant status (TOS) and oxidant status index (OSI) values of the amikacin
      group were significantly higher than those of the trimetazidine + amikacin group.
      The total antioxidant status (TAS) values of the amikacin group were lower than
      those of the trimetazidine + amikacin group. CONCLUSIONS: The audiologic tests
      and biochemical parameters investigated in this study both point to the
      protective effect of trimetazidine against amikacin-induced ototoxicity.

PMID- 24582076
TI  - Prenatal consultation with the pediatric otolaryngologist.
AB  - OBJECTIVES: To examine the spectrum of fetal head and neck anomalies that may
      prompt prenatal referral and to determine the frequency of these consultations.
      STUDY DESIGN: Case series with chart review. METHODS: The billing databases of
      two urban pediatric otolaryngology practices were queried for ICD-9 codes
      corresponding to fetal anomalies between January 2010 and December 2012. The
      pediatric otolaryngology practices in this study evaluate all fetal head and neck
      anomalies referred to their respective institutions, including craniofacial
      disorders. RESULTS: Over a three-year period, 53 women presented for fetal
      otolaryngology consultation, with each practice seeing approximately one
      consultation every 6 weeks (every 5 weeks (JDS) and every 7 weeks (ARS)). The
      average maternal and gestational age at presentation were 28.7 years and 27.2
      weeks, respectively. 83% of the cases (n = 44) involved some form of cleft lip
      with or without cleft palate. Other head and neck anomalies included fetal
      goiter/other congenital neck mass (9% (n = 5)) and micrognathia (6% (n = 3)).
      Macroglossia (n = 1) and facial cleft (n = 1) each accounted for 2% of cases.
      Cleft mothers presented earlier in pregnancy (average 26.8 weeks) than those with
      a neck mass (average 32.3 weeks) (p < 0.05). Only 3 cases (6%) merited ex utero
      intrapartum treatment. CONCLUSIONS: Depending on the referral practices at a
      given medical center, craniofacial surgeons rather than pediatric
      otolaryngologists may be evaluating the majority of fetal head and neck
      anomalies, as orofacial clefts account for most prenatal consultations. The wide
      spectrum of congenital neck masses may or may not demand monitoring of the airway
      during the peripartum period.

PMID- 24582077
TI  - Otitis media: is precursor of delayed reading in Arabic speaking children?
AB  - OBJECTIVE: To investigate the relation between otitis media in the language
      acquisition years and the occurrence of delayed reading between the ages of 7 and
      10. METHOD: Participants were 40 children, half of whom had a history of otitis
      media between the ages of birth and three years and half who were free of the
      disease. These children, now ages 7-10, were tested with the Stanford Beint and
      Arabic Dyslexia Assessment Test. RESULTS: Children with a history of otitis media
      scored over a year below grade level in reading and significantly below controls
      on Arabic Dyslexia Assessment tests as well as on the Verbal IQ factor on the
      Stanford Binet. CONCLUSIONS: Children with early onset otitis media (birth to
      three years) tend to be at greater risk for delayed reading than age-matched
      controls.

PMID- 24582078
TI  - Facial approximation of 'angel': case specific methodological review.
AB  - A forensic facial approximation is typically undertaken to generate further leads
      to identity of the deceased, and over the past ten years there has been a
      considerable increase in the number of verified relationships concerning the
      skull and likely facial appearance. This paper describes the evidence and methods
      used to approximate the face and facial features of a young woman whose remains
      were found in the Belanglo State Forest (New South Wales, Australia) in August
      2010. A review of methodologically analogous forensic facial approximations (i.e.
      involving some degree of manual manipulation to achieve the results), and
      published in international academic journals since 2000, indicates that it is
      common for methodological description to be minimal. Furthermore, what
      information is provided clearly shows a surprisingly enduring preference for
      applying 'legacy' skull-soft tissue relationships, despite most of these
      recommendations having been proven invalid. 

PMID- 24582079
TI  - Search protocols for hidden forensic objects beneath floors and within walls.
AB  - The burial of objects (human remains, explosives, weapons) below or behind
      concrete, brick, plaster or tiling may be associated with serious crime and are
      difficult locations to search. These are quite common forensic search scenarios
      but little has been published on them to-date. Most documented discoveries are
      accidental or from suspect/witness testimony. The problem in locating such hidden
      objects means a random or chance-based approach is not advisable. A preliminary
      strategy is presented here, based on previous studies, augmented by primary
      research where new technology or applications are required. This blend allows a
      rudimentary search workflow, from remote desktop study, to non-destructive
      investigation through to recommendations as to how the above may inform
      excavation, demonstrated here with a case study from a homicide investigation.
      Published case studies on the search for human remains demonstrate the problems
      encountered when trying to find and recover sealed-in and sealed-over locations.
      Established methods include desktop study, photography, geophysics and search
      dogs: these are integrated with new technology (LiDAR and laser scanning;
      photographic rectification; close-quarter aerial imagery; ground-penetrating
      radar on walls and gamma-ray/neutron activation radiography) to propose this
      possible search strategy. 

PMID- 24582080
TI  - In situ silver nanoparticles synthesis in agarose film supported on filter paper
      and its application as highly efficient SERS test stripes.
AB  - Highly efficient multifunctional agarose SERS test stripes has been fabricated by
      a convenient facile approach. SERS stripes were found to be highly sensitive,
      robust, and capable to alleviate the two major drawbacks of filter paper based
      SERS substrate i.e. the weak adhesion of plasmonic nanoparticles and the
      diffusion of analyte into the paper surface. The fabricated stripes have been
      used successfully for the ultra-trace detection of analytes of forensic interest
      including a dye, pesticide and explosive. 

PMID- 24582081
TI  - Changing treatment paradigms for patients with plasma cell myeloma: impact upon
      immune determinants of infection.
AB  - Plasma cell myeloma (PCM) is increasing in prevalence in older age groups and
      infective complications are a leading cause of mortality. Patients with PCM are
      at increased risk of severe infections, having deficits in many arms of the
      immune system due to disease and treatment-related factors. Treatment of PCM has
      evolved over time with significant impacts on immune function resulting in
      changing rates and pattern of infection. Recently, there has been a paradigm
      shift in the treatment of PCM with the use of immunomodulatory drugs and
      proteasome inhibitors becoming the standard of care. These drugs have wide
      ranging effects on the immune system but their impact on infection risk and
      aetiology remain unclear. The aims of this review are to discuss the impact of
      patient, disease and treatment factors on immune function over time for patients
      with PCM and to correlate immune deficits with the incidence and aetiology of
      infections seen clinically in these patients. Preventative measures and the need
      for clinically relevant tools to enable infective profiling of patients with PCM
      are discussed. 

PMID- 24582082
TI  - Lack of interleukin-1alpha in Kupffer cells attenuates liver inflammation and
      expression of inflammatory cytokines in hypercholesterolaemic mice.
AB  - BACKGROUND: The role of Kupffer cell interleukin (IL)-1 in non-alcoholic
      steatohepatitis development remains unclear. AIMS: To evaluate the role of
      Kupffer cell IL-1alpha, IL-1beta or IL-1 receptor type-1 (IL-1R1) in
      steatohepatitis. METHODS: C57BL/6 mice were irradiated and transplanted with bone
      marrow-derived cells from WT, IL-1alpha-/-, IL-1beta-/- or IL-1R1-/- mice
      combined with Kupffer cell ablation with Gadolinium Chloride, and fed atherogenic
      diet. Plasma and liver triglycerides and cholesterol, serum alanine
      aminotransferase (ALT), liver histology and expression levels of inflammatory
      genes were assessed. RESULTS: The ablation and replacement of Kupffer cells with
      bone marrow-derived cells was confirmed. The atherogenic diet elevated plasma and
      liver cholesterol, reduced plasma and liver triglycerides and increased serum ALT
      levels in all groups. Steatosis and steatohepatitis were induced, but without
      liver fibrosis. A reduction in the severity of portal inflammation was observed
      only in mice with Kupffer cell deficiency of IL-1alpha. Accordingly, liver mRNA
      levels of inflammatory genes encoding for IL-1alpha, IL-1beta, TNFalpha, SAA1 and
      IL-6 were significantly lower in mice with Kupffer cell deficiency of IL-1alpha
      compared to WT mice. CONCLUSION: Selective deficiency of IL-1alpha in Kupffer
      cells reduces liver inflammation and expression of inflammatory cytokines, which
      may implicate Kupffer cell-derived IL-1alpha in steatohepatitis development.

PMID- 24582083
TI  - Long-term follow-up of children who underwent severe hypospadias repair using an
      online survey with validated questionnaires.
AB  - OBJECTIVE: Few studies of hypospadias repair in childhood have used validated
      questionnaires to investigate outcomes of cosmesis, urinary function, and sexual
      function in adulthood. We sought to investigate long-term outcomes in adult
      patients who had undergone severe hypospadias repair as children using an
      existing web-based application available to multiple institutions in order to
      develop an online patient survey of previously validated questionnaires.
      MATERIALS AND METHODS: Patients aged 18 years or older who underwent severe
      hypospadias repair between 1992 and 1997 at our institution were contacted to
      complete an online survey. Through medical chart reviews, we analyzed the
      location of meatus, type of repair, and complications. The online survey included
      questions about penile appearance, and validated questionnaires to assess urinary
      and sexual function. RESULTS: Of 58 patients who met the inclusion criteria, we
      contacted 19, and 13 completed the survey. Fifty-nine percent had complications,
      with an average of 2.2 procedures per patient. Most (85.0%) were satisfied with
      penile appearance, although 38.0% had residual penile curvature. Hypospadias
      patients had mean lower orgasmic function than normal controls. Mean scores for
      urinary function and other domains of sexual function were similar to normal
      controls. CONCLUSIONS: Although the majority of adult patients were satisfied
      with the outcomes of penile appearance, urinary function, and sexual function,
      our online survey suggests decreased lower orgasmic function as measured by
      validated questionnaire. An online survey accessible to multiple institutions
      with validated questionnaires may facilitate assessment of long-term hypospadias
      results.

PMID- 24582084
TI  - Simplified criteria for selecting patients for vertebral fracture assessment.
AB  - The 2013 Position Development Conference of the International Society for
      Clinical Densitometry (ISCD) has adopted simplified indications for vertebral
      fracture assessment (VFA) based on an analysis of the Study of Osteoporotic
      Fractures (SOF). This showed that a simpler regression model, which included only
      age, bone mineral density (BMD), and height loss, was able to differentiate women
      with vertebral fractures from those without vertebral fractures almost as well as
      more complex models. We aimed to verify these findings in 1228 women referred for
      BMD testing and determine if the 2013 ISCD indications for VFA would perform as
      well the 2007 indications. The simple and complex SOF-based models were similar
      in terms of sensitivity (88.4% vs 89.4%), specificity (44.4% vs 45.5%), positive
      (25.9% vs 26.5%) and negative (94.5% vs 95.1%) predictive values, and area under
      the receiver operating characteristics curve (AUROC) (0.664 vs 0.674). The 2013
      and 2007 ISCD VFA indications did not differ significantly in terms of
      sensitivity (88.2% vs 91.3%), specificity (41.3% vs 37.5%), positive (25.3% vs
      22.9%) and negative (93.9% vs 95.5%) predictive values, and AUROC (0.648 vs
      0.644). Our study provides support for the use of the simplified 2013 ISCD VFA
      indications as a practical approach to VFA testing. 

PMID- 24582086
TI  - Creation of an age-adjusted, dual-energy x-ray absorptiometry-derived trabecular
      bone score curve for the lumbar spine in non-Hispanic US White women.
AB  - The trabecular bone score (TBS, Med-Imaps, Pessac, France) is an index of bone
      microarchitecture texture extracted from anteroposterior dual-energy X-ray
      absorptiometry images of the spine. Previous studies have documented the ability
      of TBS of the spine to differentiate between women with and without fractures
      among age- and areal bone mineral density (aBMD)-matched controls, as well as to
      predict future fractures. In this cross-sectional analysis of data collected from
      3 geographically dispersed facilities in the United States, we investigated age
      related changes in the microarchitecture of lumbar vertebrae as assessed by TBS
      in a cohort of non-Hispanic US white American women. All subjects were 30 yr of
      age and older and had an L1-L4aBMDZ-score within +/-2 SD of the population mean.
      Individuals were excluded if they had fractures, were on any osteoporosis
      treatment, or had any illness that would be expected to impact bone metabolism.
      All data were extracted from Prodigy dual-energy X-ray absorptiometry devices (GE
      Lunar, Madison, WI). Cross-calibrations between the 3 participating centers were
      performed for TBS and aBMD. aBMD and TBS were evaluated for spine L1-L4 but also
      for all other possible vertebral combinations. To validate the cohort, a
      comparison between the aBMD normative data of our cohort and US non-Hispanic
      white Lunar data provided by the manufacturer was performed. A database of 619
      non-Hispanic US white women, ages 30-90 yr, was created. aBMD normative data
      obtained from this cohort were not statistically different from the non-Hispanic
      US white Lunar normative data provided by the manufacturer (p = 0.30). This
      outcome thereby indirectly validates our cohort. TBS values at L1-L4 were weakly
      inversely correlated with body mass index (r = -0.17) and weight (r = -0.16) and
      not correlated with height. TBS values for all lumbar vertebral combinations
      decreased significantly with age. There was a linear decrease of 16.0% (-2.47 T
      score) in TBS at L1-L4 between 45 and 90 yr of age (vs. -2.34 for aBMD).
      Microarchitectural loss rate increased after age 65 by 50% (-0.004 to -0.006).
      Similar results were obtained for other combinations of lumbar vertebra. TBS, an
      index of bone microarchitectural texture, decreases with advancing age in non
      Hispanic US white women. Little change in TBS is observed between ages 30 and 45.
      Thereafter, a progressive decrease is observed with advancing age. The changes we
      observed in these American women are similar to that previously reported for a
      French population of white women (r(2) > 0.99). This reference database will
      facilitate the use of TBS to assess bone microarchitectural deterioration in
      clinical practice. 

PMID- 24582085
TI  - Prediction models of prevalent radiographic vertebral fractures among older
      women.
AB  - It is unknown how well prediction models incorporating multiple risk factors
      identify women with radiographic prevalent vertebral fracture (PVFx) compared
      with simpler models and what their value might be in clinical practice to select
      older women for lateral spine imaging. We compared 4 regression models for
      predicting PVFx in women aged 68 y and older enrolled in the Study of
      Osteoporotic Fractures with a femoral neck T-score <= -1.0, using area under
      receiving operator characteristic curves (AUROC) and a net reclassification
      index. The AUROC for a model with age, femoral neck bone mineral density,
      historical height loss (HHL), prior nonspine fracture, body mass index, back
      pain, and grip strength was only minimally better than that of a more
      parsimonious model with age, femoral neck bone mineral density, and historical
      height loss (AUROC 0.689 vs 0.679, p values for difference in 5 bootstrapped
      samples <0.001-0.35). The prevalence of PVFx among this older population of
      Caucasian women remained more than 20% even when women with low probability of
      PVFx, as estimated by the prediction models, were included in the screened
      population. These results suggest that lateral spine imaging is appropriate to
      consider for all Caucasian women aged 70 y and older with low bone mass to
      identify those with PVFx. 

PMID- 24582087
TI  - A novel gas chromatography mass spectrometry-based serum diagnostic and
      assessment approach to ulcerative colitis.
AB  - BACKGROUND & AIMS: To improve the clinical course of ulcerative colitis (UC),
      more accurate serum diagnostic and assessment methods are required. We used serum
      metabolomics to develop diagnostic and assessment methods for UC. METHODS: Sera
      from UC patients, Crohn's disease (CD) patients, and healthy volunteers (HV) were
      collected at multiple institutions. The UC and HV were randomly allocated to the
      training or validation set, and their serum metabolites were analyzed by gas
      chromatography mass spectrometry (GC/MS). Using the training set, diagnostic and
      assessment models for UC were established by multiple logistic regression
      analysis. Then, the models were assessed using the validation set. Additionally,
      to establish a diagnostic model for discriminating UC from CD, the CD patients'
      data were used. RESULTS: The diagnostic model for discriminating UC from HV
      demonstrated an AUC of 0.988, 93.33% sensitivity, and 95.00% specificity in the
      training set and 95.00% sensitivity and 98.33% specificity in the validation set.
      Another model for discriminating UC from CD exhibited an AUC of 0.965, 85.00%
      sensitivity, and 97.44% specificity in the training set and 83.33% sensitivity in
      the validation set. The model for assessing UC showed an AUC of 0.967, 84.62%
      sensitivity, and 88.23% specificity in the training set and 84.62% sensitivity,
      91.18% specificity, and a significant correlation with the clinical activity
      index (rs=0.7371, P<0.0001) in the validation set. CONCLUSIONS: Our models
      demonstrated high performance and might lead to the development of a novel
      treatment selection method based on UC condition.

PMID- 24582089
TI  - Metabolic syndrome.
AB  - Metabolic syndrome is not a disease per se, but is a term that highlights traits
      that may have an increased risk of disease, approximately 2-fold for
      cardiovascular disease and 5-fold or more for type 2 diabetes mellitus. Obesity
      and insulin resistance are believed to be at the core of most cases of metabolic
      syndrome, although further research is required to truly understand the
      pathophysiology behind the syndrome and the gene-environment interactions that
      increase susceptibility. The mainstay of treatment remains lifestyle changes with
      exercise and diet to induce weight loss and pharmacologic intervention to treat
      atherogenic dyslipidemia, hypertension, and hyperglycemia. 

PMID- 24582090
TI  - Cardiovascular disease in diabetes mellitus: risk factors and medical therapy.
AB  - Cardiovascular disease is a serious complication of diabetes mellitus. In the
      last 2 decades, great strides have been made in reducing microvascular
      complications in patients with diabetes through improving glycemic control.
      Decreasing rates of cardiovascular events have proved to be more difficult than
      simply intensifying the management of hyperglycemia. A tremendous effort has been
      made to deepen understanding of cardiovascular disease in diabetes and to
      formulate the best treatment approach. This review summarizes the current state
      of knowledge and discusses areas of uncertainty in the care of patients with
      diabetes who are at risk for cardiovascular disease. 

PMID- 24582088
TI  - Clinical outcomes and survival of advanced renal cancer patients in phase I
      clinical trials.
AB  - BACKGROUND/INTRODUCTION: The purpose of this study was to describe the basic
      demographic characteristics, and analyze the response and survival experience of
      advanced renal cancer subjects treated in a phase I trial. PATIENTS AND METHODS:
      We conducted a retrospective observational study in 70 renal cancer patients
      participating in 25 phase I trials. Descriptive statistics, Kaplan-Meier, and
      multivariate Cox proportional hazards analyses were used to examine factors
      associated with time from study entry to treatment failure (TTF) and survival.
      RESULTS: The median age at diagnosis was 56.50 years. Eastern Cooperative
      Oncology Group (ECOG) performance status was 0 for 23.19% (n = 16) of the
      patients; 49.18% (n = 30) had received 2 or more previous lines of systemic
      therapy; and 84.29% (n = 59) of patients had 2 or more metastatic sites. A median
      number of 4.00 cycles of treatment was delivered. Four partial responses (6.25%)
      and 38 cases of stable disease lasting > 4 months (43.75%) were observed. The
      median TTF was 16.00 weeks. In multivariate analyses, men and patients with
      lactate dehydrogenase > 1.5 times the upper limit of normal had a shorter TTF.
      The median overall survival was 45.57 weeks (319.00 days). In multivariate
      analysis, factors predicting shorter survival were ECOG performance status >= 1
      (P = .023), age younger than 60 years (P = .015), albumin < 3.4 g/dL (P = .042),
      and liver metastases (P = .010). CONCLUSION: Advanced renal cancer patients with
      select clinical characteristics could consider phase I trials after exhausting
      standard therapeutic options.

PMID- 24582091
TI  - The relationships between cardiovascular disease and diabetes: focus on
      pathogenesis.
AB  - There is a looming global epidemic of obesity and diabetes. Of all the end-organ
      effects caused by diabetes, the cardiovascular system is particularly susceptible
      to the biologic perturbations caused by this disease, and many patients may die
      from diabetes-related cardiovascular complications. Substantial progress has been
      made in understanding the pathobiology of the diabetic vasculature and heart.
      Clinical studies have illuminated the optimal way to treat patients with
      cardiovascular manifestations of this disease. This article reviews these aspects
      of diabetes and the cardiovascular system, broadly classified into diabetic
      vascular disease, diabetic cardiomyopathy, and the clinical management of the
      diabetic cardiovascular disease patient. 

PMID- 24582092
TI  - Interventions for coronary artery disease (surgery vs angioplasty) in diabetic
      patients.
AB  - Patients with diabetes develop more widespread and more severe atherosclerotic
      coronary artery disease than patients without diabetes. Medical management of
      this coronary disease is inferior to revascularization for more complex or more
      widespread disease. Revascularization by percutaneous intervention (PCI) for
      patients with diabetes is associated with high mortality and complication rates.
      Surgical revascularization by coronary artery bypass grafting, yields superior
      results to PCI for patients with diabetes and coronary artery disease. Patients
      with diabetes benefit from the same medical management of their coronary artery
      disease and secondary risk modification as patients without diabetes. 

PMID- 24582095
TI  - Polycystic ovary syndrome.
AB  - Polycystic ovary syndrome (PCOS), a heterogeneous and chronic condition, today
      affects about 5% of women of reproductive age. PCOS is strongly associated with
      states of insulin resistance and hyperinsulinemia. Risk factors include genetics,
      metabolic profiles, and the in utero environment. Long-term consequences of PCOS
      include metabolic complications such as diabetes, obesity, and cardiovascular
      disease. Dysregulation of insulin action is closely linked to the pathogenesis of
      PCOS. However, whether insulin resistance is the causative factor in the
      development of PCOS remains to be ascertained. Moreover, the mechanism by which
      insulin resistance may lead to reproductive dysfunction requires further
      elucidation. 

PMID- 24582096
TI  - Peripheral arterial disease.
AB  - Peripheral arterial disease (PAD) is an atherosclerotic-driven condition that
      remains underdiagnosed and undertreated. In diabetic patients, PAD begins early,
      progresses rapidly, and is frequently asymptomatic, making it difficult to
      diagnose. Strict management of the metabolic instigators and use of screening
      techniques for PAD in diabetes can facilitate early diagnosis and reduce
      progression. Exercise is an equally effective treatment option in improving
      walking distance. Early revascularization must be offered early in suitable
      patients. Surgical bypass and endovascular revascularization are complementary
      and the choice of intervention should be applied appropriately by a
      multidisciplinary vascular team on a selective, patient-specific basis. 

PMID- 24582094
TI  - Type 2 diabetes mellitus and hypertension: an update.
AB  - Patients with hypertension and type 2 diabetes are at increased risk of
      cardiovascular and chronic renal disease. Factors involved in the pathogenesis of
      both hypertension and type 2 diabetes include inappropriate activation of the
      renin-angiotensin-aldosterone system, oxidative stress, inflammation, impaired
      insulin-mediated vasodilatation, augmented sympathetic nervous system activation,
      altered innate and adaptive immunity, and abnormal sodium processing by the
      kidney. The renin-angiotensin-aldosterone system blockade is a key therapeutic
      strategy in the treatment of hypertension in type 2 diabetes. Emerging therapies
      for resistant hypertension as often exists in patients with diabetes, include
      renal denervation and carotid body denervation. 

PMID- 24582097
TI  - Diabetes and cancer.
AB  - Diabetes is a worldwide health problem that has been increasingly associated with
      various types of cancers. Epidemiologic studies have shown an increased risk of
      cancer as well as a higher mortality rate in patients with type 2 diabetes (T2D).
      The biologic mechanisms driving the link between T2D and cancer are not well
      understood. In this review, various proposed mechanisms are addressed to explain
      the relationship between T2D and cancer. Understanding the precise mechanisms
      that link T2D, obesity, and the metabolic syndrome with cancer will aid in
      developing treatments that will reduce mortality in individuals with T2D and
      cancer. 

PMID- 24582093
TI  - Mechanisms of glucocorticoid-induced insulin resistance: focus on adipose tissue
      function and lipid metabolism.
AB  - Glucocorticoids (GCs) are critical in the regulation of the stress response,
      inflammation and energy homeostasis. Excessive GC exposure results in whole-body
      insulin resistance, obesity, cardiovascular disease, and ultimately decreased
      survival, despite their potent anti-inflammatory effects. This apparent paradox
      may be explained by the complex actions of GCs on adipose tissue functionality.
      The wide prevalence of oral GC therapy makes their adverse systemic effects an
      important yet incompletely understood clinical problem. This article reviews the
      mechanisms by which supraphysiologic GC exposure promotes insulin resistance,
      focusing in particular on the effects on adipose tissue function and lipid
      metabolism. 

PMID- 24582098
TI  - Obstructive sleep apnea: an unexpected cause of insulin resistance and diabetes.
AB  - Obstructive sleep apnea (OSA) is prevalent with type 2 diabetes. Conversely,
      nondiabetic patients with OSA are at increased risk of developing insulin
      resistance and diabetes. These disorders independently contribute to increased
      cardiovascular and cerebrovascular morbidity and mortality. The pathophysiology
      of OSA may help explain these associations. Evidence demonstrates that treatment
      of OSA with continuous positive airway pressure may lead to improvement in
      insulin sensitivity, hemoglobin A1c, systemic hypertension, and other components
      of the metabolic syndrome. Recognizing and treating OSA in patients with insulin
      resistance or diabetes ameliorates OSA-related symptoms and improves
      cardiometabolic risk. 

PMID- 24582100
TI  - Osteoporosis-associated fracture and diabetes.
AB  - Osteoporosis and diabetes mellitus are chronic diseases with significant
      associated morbidity and mortality. Recent evidence suggests that both type 1 and
      type 2 diabetes are associated with an increased fracture risk. Fracture as a
      complication of diabetes must be considered when evaluating and treating patients
      with diabetes. 

PMID- 24582099
TI  - Vitamin D and diabetes.
AB  - There has been increasing evidence that vitamin D may have a role in modifying
      risk of diabetes. Vitamin D has both direct and indirect effects on various
      mechanisms related to the pathophysiology of type 2 diabetes, including
      pancreatic beta cell dysfunction, impaired insulin action and systemic
      inflammation. This article describes the biologic plausibility behind the
      potential association between vitamin D and type 2 diabetes and summarizes the
      current evidence from human studies that suggests but does not prove a relation
      between vitamin D and type 2 diabetes, and briefly reports on the potential
      association between vitamin D and type 1 diabetes. 

PMID- 24582102
TI  - Interactions between diabetes and anxiety and depression: implications for
      treatment.
AB  - Anxiety or depression may be a risk factor for the development of diabetes. This
      relationship may occur through a combination of genetic predispositions;
      epigenetic contingencies; exacerbating conditions such as metabolic syndrome (a
      precursor to diabetes); and other serious medical conditions. Medications used to
      treat anxiety and depression have significant side effects, such as weight gain,
      further increasing the possibility of developing diabetes. These components
      combine, interact, and reassemble to create a precarious system for persons with,
      or predisposed to, diabetes. Clinicians must be aware of these interrelationships
      to adequately treat the disease. 

PMID- 24582103
TI  - Diabetes mellitus: associated conditions. Foreword.

PMID- 24582104
TI  - Why are associated conditions important?

PMID- 24582101
TI  - Relationships between diabetes and cognitive impairment.
AB  - Epidemics of obesity, diabetes, nonalcoholic fatty liver disease, and cognitive
      impairment/Alzheimer disease have emerged over the past 3 to 4 decades. These
      diseases share in common target-organ insulin resistance with a constellation of
      molecular and biochemical abnormalities that lead to organ/tissue degeneration
      over time. This article discusses the fundamental links among these diseases and
      how peripheral organ insulin resistance diseases contribute to cognitive
      impairment and neurodegeneration. A future role of endocrinologists and
      diabetologists could be to provide integrative diagnostic and treatment
      approaches for this collection of diseases that seem to share pathophysiological
      and pathogenetic bases. 

PMID- 24582105
TI  - Hypotonic versus isotonic fluids in hospitalized children: a systematic review
      and meta-analysis.
AB  - OBJECTIVE: To determine whether the use of hypotonic vs isotonic maintenance
      fluids confers an increased risk of hyponatremia in hospitalized children. STUDY
      DESIGN: A search of MEDLINE (1946 to January 2013), the Cochrane Central Registry
      (1991 to December 2012), Cumulative Index for Nursing and Allied Health
      Literature (1990 to December 2012), and Pediatric Academic Societies (2000-2012)
      abstracts was conducted using the terms "hypotonic fluids/saline/solutions" and
      "isotonic fluids/saline/solutions," and citations were reviewed using a
      predefined protocol. Data on the primary and secondary outcomes were extracted
      from original articles by 2 authors independently. Meta-analyses of the primary
      and secondary outcomes were performed when possible. RESULTS: A total of 1634
      citations were screened. Ten studies (n = 893) identified as independent
      randomized controlled trials were included. Five studies examined subjects in the
      intensive care unit setting, including 4 on regular wards and 1 in a mixed
      setting. In hospitalized children receiving maintenance intravenous fluids,
      hyponatremia was seen more often in those receiving hypotonic fluids than in
      those receiving isotonic fluids, with an overall relative risk of 2.37 (95% CI,
      1.72-3.26). Receipt of hypotonic fluids was associated with a relative risk of
      moderate hyponatremia (<130 mmol/L) of 6.1 (95% CI, 2.2-17.3). A subgroup
      analysis of hypotonic fluids with half-normal saline found a relative risk of
      hyponatremia of 2.42 (95% CI, 1.32-4.45). CONCLUSION: In hospitalized children in
      intensive care and postoperative settings, the administration of hypotonic
      maintenance fluids increases the risk of hyponatremia when compared with
      administration of isotonic fluids. For patients on general wards, insufficient
      data are available based on the reviewed studies, and individual risk factors
      must be assessed.

PMID- 24582106
TI  - Comparison of newborn screening protocols for congenital adrenal hyperplasia in
      preterm infants.
AB  - OBJECTIVE: To compare 2 screening protocols performed concurrently in Minnesota:
      (1) liquid chromatography tandem mass spectrometry steroid profiling as a second
      tier test on positive fluoroimmunoassay (FIA) results; and (2) low-birthweight 3
      screen protocol (FIA tests at <48 hours, 2 weeks, 4 weeks) on all infants <1800
      g, regardless of result. STUDY DESIGN: Population-based study of all <1800 g
      infants (n = 8739) born in Minnesota from 2004-2010 comparing newborn screening
      performance metrics of 2-tier (FIA + liquid chromatography tandem mass
      spectrometry) protocol (2004-2010) vs 1-tier (FIA) low-birthweight 3-screen
      protocol (2006-2010). False positive (FP) rates were calculated per infant's
      final confirmatory result. Protocol results used in different time periods (2004
      2005 vs 2006-2010) were compared by 2-sample tests of proportions; results of
      both protocols for 2006-2010 were compared by McNemar test. RESULTS: First-tier
      testing of final dried blood spot result (n = 6625) of the low-birthweight 3
      screen protocol during 2006-2010 reduced the FP rate more than 5-fold (P < .0001)
      compared with 2-tier testing of a single dried blood spot (n = 2114) from 2004
      2005. In comparing results (n = 6625) of both protocols from 2006-2010, first
      tier testing of final dried blood spot accounted for 23% of FPs; second-tier
      testing of the first dried blood spot accounted for 77%, yielding significantly
      more FP results (McNemar test, P < .0001). CONCLUSION: Timing of dried blood spot
      collection rather than assay used played a more important role in reducing FP
      results of congenital adrenal hyperplasia newborn screening in low birthweight
      infants.

PMID- 24582108
TI  - [Hemoptysia and postoperative pulmonary edema after general anesthesia for
      amygdalectomy].
AB  - Acute postoperative negative pressure pulmonary edema with hemoptysia as a
      complication of general anesthesia is seldom. Its is related to an obstacle on
      airway, with important negative intrathoracic depression during inspiration
      leading to pulmonary edema and hemoptysia. Physiopathology and treatment of such
      complication have been discussed. 

PMID- 24582107
TI  - Bisphenol A (BPA) pharmacokinetics with daily oral bolus or continuous exposure
      via silastic capsules in pregnant rhesus monkeys: Relevance for human exposures.
AB  - We measured serum dBPA in non-pregnant and pregnant female rhesus monkeys,
      fetuses and amniotic fluid. dBPA was administered by a daily oral bolus or sc
      implantation of Silastic capsules; both resulted in daily average serum
      unconjugated dBPA concentrations of <1ng/ml. We observed lower serum
      concentrations of unconjugated dBPA in pregnant females relative to pre-pregnancy
      values, and generally lower concentrations in fetal serum than in maternal serum.
      Differences in pharmacokinetics of dBPA were evident between pre-pregnancy, early
      and late pregnancy, likely reflecting changes in maternal, fetal and placental
      physiology. The serum ratio of conjugated to unconjugated dBPA after continuous
      sc release of dBPA was similar to values reported in human biomonitoring studies
      and markedly lower than with oral administration, suggesting oral bolus exposure
      is not an appropriate human exposure model. We report elsewhere that there were
      numerous adverse effects on fetuses exposed to very low serum dBPA in these
      studies. 

PMID- 24582109
TI  - [Locating the cricothyroid membrane in learning phase: value of
      ultrasonography?].
AB  - OBJECTIVES: Emergency cricothyroidotomy is recommended as life-saving maneuver
      when mask ventilation and tracheal intubation are impossible. It requires the
      puncture of the cricothyroid membrane (CTM) whose clinical identification is
      difficult. The objective of this study is to evaluate if ultrasound can help
      locating the CTM by comparing palpation and ultrasonographic evaluation. PATIENTS
      AND METHODS: After ultrasound localization of CTM by a referent physician in two
      overweight volunteers, twelve residents without prior anatomy recall, defined by
      palpation an entry point for CTM. After a rapid training in CTM ultrasound
      localization, residents identified an ultrasound-guided puncture point. For each
      puncture site were registered: relevance, time and ease to localization. Six
      months later, residents renewed clinical and ultrasound identification of CTM on
      the same subjects. RESULTS: The CTM was accurately identified by palpation and
      ultrasound by 46% and 100% of residents respectively (P<0.05). Six months later,
      residents remained more effective identifying CTM with ultrasound than with
      palpation (78% vs. 33%) (P<0.05). Time to localization of CTM by palpation in the
      2 volunteers was 15 s [11-18] and 24 s [9-39] (average [CI 95%]) whereas it was
      21 s [16-25 s] and 28 s [19-36] by ultrasound respectively (ns). The ultrasound
      identification of CTM was also considered easier than clinical identification.
      CONCLUSION: Following a limited training phase, ultrasound allowed a more
      effective localization of CTM by residents when compared to clinical palpation in
      overweight patients. This benefit remained significant when assessment was
      repeated 6 months later.

PMID- 24582110
TI  - In vitro evaluation of diffusion of lidocaine and alkalinized lidocaine through
      the polyurethane membrane of the endotracheal tube.
AB  - OBJECTIVES: Endotracheal tube (ETT) and its inflated cuff are likely to induce
      specific reactivity at the emergence time. In ICU, the tolerance of the ETT cuff
      could be a part of patient agitation and increased of sedation. MATERIALS AND
      METHODS: Using specific ICU ETT cuff (thin polyurethane cuff), we perform an in
      vitro evaluation of diffusion of lidocaine and alkalinized lidocaine (L-B) across
      the PU cuff for a long duration. We evaluate the safety of this procedure by a
      daily injection into the cuff. RESULTS: With lidocaine alone, we observed a low
      rate of diffusion through the cuff (<8% over 24h), whereas the L-B solution had a
      high diffusion (>90% over 24h). The released profiles were similar from day 0 to
      day 8, and no cuff rupture was reported over the 8-day study. CONCLUSION: The
      safety, controlled release, and lack of deleterious effects on cuff membrane were
      confirmed. In case of unexpected cuff rupture, an adequate determination of the
      mixture allows to obtain a safe solution with the achievement of a physiological
      pH (7.4) and the small dose of lidocaine (40 mg).

PMID- 24582111
TI  - Does sevoflurane preserve regional cerebral oxygen saturation measured by near
      infrared spectroscopy better than propofol?
AB  - OBJECTIVE: The aim of this study was to compare the effect of sevoflurane and
      propofol on cerebral oxygenation, using regional cerebral oxygen saturation
      (SrO2) measured by near-infrared spectroscopy (NIRS). STUDY DESIGN: Prospective,
      randomized, controlled study. PATIENTS AND METHODS: Fifty-four patients aged
      between 18 and 65 years who underwent elective minor surgery (tumorectomy for
      breast cancer or inguinal hernia repair) were randomly assigned to receive
      sevoflurane or propofol anaesthesia. Exclusion criteria included pre-existing
      cerebrovascular diseases, anaemia, ASA >III, blood loss >=200 mL, arterial
      hypotension, baseline pulse oximetry <97%, sign of sensor low quality of SrO2 or
      bispectral index, and patients with a forehead area <6.5cm. SrO2, bispectral
      index, haemodynamic data and anaesthetic doses were recorded during surgery.
      RESULTS: A total of 48 patients were included in the final analysis (24 in each
      group). There were no significant differences in mean, minimum and maximum SrO2
      between sevoflurane and propofol groups. The relative maximum decrease was higher
      in propofol anaesthesia than sevoflurane anaesthesia (9.6+/-10.7 versus 4.2+/
      7.2%; P=0.048). Cerebral desaturation (20% reduction from SrO2 baseline during 15
      seconds) occurred in 4 patients in propofol group exclusively (P=0.109). SrO2
      adjusted for baseline was higher in the sevoflurane group than in the propofol
      group (67.3+/-1.8% versus 64.2+/-1.7%; P=0.018). There were no significant
      differences in haemodynamic parameters between the two groups. CONCLUSIONS:
      Cerebral cortical oxygenation measured by NIRS may be better preserved with
      sevoflurane than with propofol. These findings suggest that sevoflurane
      anaesthesia could be a good option in patients with compromised cerebral
      oxygenation, given the absence of intracranial hypertension. Further studies with
      larger sample sizes are required to support our results.

PMID- 24582112
TI  - Incidence and prediction of inadequate preoxygenation before induction of
      anaesthesia.
AB  - BACKGROUND: Preoxygenation aims to obtain an expired oxygen fraction (FEO2)>=90%.
      Little is known about the incidence and predictors of inadequate preoxygenation
      in the clinical setting. PATIENTS AND METHODS: Over a 12-month period, 1050
      consecutive preoperative patients were prospectively included. Preoxygenation was
      performed for 3minutes with a facial mask using a machine circuit and 12-L/min
      oxygen flow. Inadequate preoxygenation was defined as an FEO2<90%. A logistic
      regression was performed to identify incidence and independent predictors.
      RESULTS: The patient characteristics were: age 51+/-20years, 47% male, BMI of
      26+/-5kg/m(2), and ASA score (median [extremes]) of 2 [1-4]. Inadequate
      preoxygenation was observed in 589 patients (56%). The effective FiO2 delivered
      was lower in the patients with inadequate preoxygenation than in those with
      adequate preoxygenation, 95+/-3% vs. 98+/-2%, P<0.001. The difference between the
      FiO2 and the FEO2 was higher (12+/-6% vs. 6+/-3%, P<0.0001) in patients with
      inadequate preoxygenation compared with those with adequate preoxygenation. The
      independent risk factors for inadequate preoxygenation were: firstly, bearded
      male (odds ratio [OR] of 9.1 [2.7-31.4] P<0.001); secondly, beardless male (OR
      2.4 [1.6-3.4] P<0.001), thirdly, ASA score of 4 (OR 9.1 [2.6-31.2] P<0.015);
      fourthly, ASA score of 2-3 (OR 2.4 [1.6-3.4] P<0.015); fifthly, lack of teeth (OR
      2.4 [1.2-4.5] P<0.006), and lastly age>55 years (OR 1.8 [1.2-2.7] P<0.005).
      CONCLUSION: Inadequate preoxygenation, defined as an FEO2 <90% despite 3-min
      tidal volume breathing, was a common occurrence. The predictive factors share an
      overlap with those previously identified for difficult mask ventilation.

PMID- 24582113
TI  - [2012, 2013, the winners are (again) the Annales Francaises d'Anesthesie et de
      Reanimation!].

PMID- 24582114
TI  - Manifestation of both emetic seizures and sylvian seizures in the same patients
      with benign partial epilepsy.
AB  - PURPOSE: Benign childhood epilepsy with centro-temporal spikes (BECTS) and
      Panayiotopoulos syndrome (PS) have different pathophysiologies and show different
      types of seizures, yet they overlap in some important respects. In an attempt to
      understand the ways in which they differ from each other and overlap each other,
      we performed a detailed investigation on patients who had both characteristic
      types of seizure manifestations, namely, sylvian seizures and emetic seizures.
      SUBJECTS AND METHODS: We recruited consecutive subjects from the EEG database of
      outpatients who had visited our hospital between 2008 and 2010 and who had been
      diagnosed with BECTS or PS. As a result, 45 patients with BECTS and 50 patients
      with PS were selected from the database. Viewing the clinical records of these 95
      patients, five patients were selected who had experienced both sylvian seizures
      and emetic seizures. Next, the clinical features and EEG findings of these five
      patients were retrospectively observed at the date of investigation: October 1,
      2011. RESULTS: We found that all the patients showed rolandic spikes when they
      had sylvian seizures, and occipital spikes or multifocal spikes when they had
      emetic seizures. We also report in detail on one patient who showed two different
      types of ictal EEG patterns: one of which started in the occipital area and the
      other of which was located in the rolandic area. CONCLUSION: Based on these
      findings, we conclude that widespread cortical hyperexcitability that includes
      the occipital area is necessary to produce the autonomic seizure manifestations
      seen in PS.

PMID- 24582115
TI  - Changes in muscle activity and stature recovery after active rehabilitation for
      chronic low back pain.
AB  - Patients with low back pain often demonstrate elevated paraspinal muscle activity
      compared to asymptomatic controls. This hyperactivity has been associated with a
      delayed rate of stature recovery following spinal loading tasks. The aim of this
      study was to investigate the changes in muscle activity and stature recovery in
      patients with chronic low back pain following an active rehabilitation programme.
      The body height recovery over a 40-min unloading period was assessed via
      stadiometry and surface electromyograms were recorded from the paraspinal muscles
      during standing. The measurements were repeated after patients had attended the
      rehabilitation programme and again at a six-month follow-up. Analysis was based
      on 17 patients who completed the post-treatment analysis and 12 of these who also
      participated in the follow-up. By the end of the six months, patients recovered
      significantly more height during the unloading session than at their initial
      visit (ES = 1.18; P < 0.01). Greater stature recovery immediately following the
      programme was associated with decreased pain (r = -0.55; P = 0.01). The increased
      height gain after six months suggests that delayed rates of recovery are not
      primarily caused by disc degeneration. Muscle activity did not decrease after
      treatment, perhaps reflecting a period of adaptation or altered patterns of motor
      control.

PMID- 24582116
TI  - A method for optimum PSA setting in the absence of a pure alpha or beta emitter
      and its application in the determination of (237)Np/(233)Pa.
AB  - In the application of liquid scintillation counting (LSC), the alpha/beta
      discrimination is carried out with the function of pulse shape analysis (PSA),
      which requires the setting of the optimum PSA level. The optimum PSA are usually
      determined by the generation of cross-over plots, whereby a pair of vials, one
      containing a pure alpha emitter and the other a pure beta emitter, is counted.
      However, in some cases such as the determination of (237)Np/(233)Pa, a pure alpha
      emitter or a pure beta emitter is not available. Therefore, we have developed a
      new approach to set the optimum PSA by measuring the sample itself of mixed
      alpha/beta emitters. The count rate of the sample in the alpha-multi-channel
      analyzer changes monotonically with the increase of the PSA, and there is always
      an inflection point which is related to the optimum PSA. By fitting the data near
      the inflection point with the function y=ax(3)+bx(2)+cx+d, we can obtain the
      optimum PSA as -b/(3a), which can be used to determine the radioactivity of
      (237)Np/(233)Pa. The results obtained with this new approach were in good
      agreement with those obtained by HPGe gamma spectrometry that was calibrated with
      an LSC sample of (237)Np/(233)Pa under a radioactive secular equilibrium. The new
      approach is promising to be used in simultaneous determination of gross alpha and
      beta emitters, especially in the absence of a pure alpha or beta emitter. 

PMID- 24582117
TI  - Plasmacytoid bladder cancer: variant histology with aggressive behavior and a new
      mode of invasion along fascial planes.
AB  - OBJECTIVE: To examine differences in disease progression and nature of tumor
      invasion that may lead to more accurate expectations of tumor behavior and
      improved management options for plasmacytoid variant (PCV) histology urothelial
      bladder cancer patients. METHODS: Using the Indiana University Bladder Cancer
      Database, we conducted a retrospective analysis of patients undergoing radical
      cystectomy from 2008 to June 2013 to identify patients with PCV, micropapillary
      variant (MPV), or nonvariant (NV) histology and either positive ureteral margins
      (+UM), paravesical surgical margins (+PSM), or lymph node (+LN) involvement.
      Pearson's chi-squared test and analysis of variance were used for descriptive
      analysis. RESULTS: Of 510 patients who met inclusion criteria, 30 had +UM on
      final pathology. The incidence of +UM in NV patients was 17 of 457 (3.7%), in MPV
      5 of 28 (17.9%), and in PCV 8 of 25 (32.0%) (P <.001). Carcinoma in situ on the
      luminal margin was noted for all cases, except in 5 of the 8 PCV patients with
      +UM, in whom retrograde longitudinal invasion along the subserosal and adventitia
      was noted. +PSM and +LN were significantly higher for both PCV (28.0%, 72.0%) and
      MPV (10.7%, 64.3%) than NV (2.6%, 18.6%, P <.001, each). CONCLUSION: PCV exhibits
      a unique pattern of spread along the ureter. This proposes a new mode of invasion
      along the fascial sheath. The incidence of +PSM and +LN liken PCV to the known
      aggressive MPV, and in conjunction with the increased incidence of +UM, may lead
      to a paradigm shift, with surgeons and pathologists being more vigilant with
      surgical margins.

PMID- 24582118
TI  - Juvenile xanthogranuloma: an unusual cause of intratesticular mass in childhood.
AB  - Juvenile xanthogranuloma (JXG) is a common histiocytic disorder of infancy and
      early childhood, most frequently presenting with cutaneous lesions. Whereas
      involvement of several visceral sites is well documented, only 4 cases of primary
      testicular JXG have been reported. Although this benign disorder typically
      presents with a favorable clinical outcome, the unusual presentation as an
      intratesticular lesion can lead to diagnostic challenges. In this study, we
      present the case of a 6-month-old male child with an incidentally discovered
      testicular mass that was diagnosed as a JXG and briefly review the existing
      literature in an attempt to bring awareness to this uncommon presentation.

PMID- 24582119
TI  - Do patient characteristics predict responsiveness to treatment of overactive
      bladder with antimuscarinic agents?
AB  - OBJECTIVE: To determine clinical and demographic characteristics associated with
      antimuscarinic treatment response using a regression model. METHODS: Adults with
      overactive bladder (OAB) symptoms for >3 months and >= 1 urgency urinary
      incontinence (UUI) episode and >= 8 micturitions per 24 hours at baseline were
      randomized to fesoterodine (8 mg), tolterodine extended-release (4 mg), or
      placebo in two 12-week, double-blind, head-to-head studies. Fesoterodine-treated
      patients received 4 mg/d during the first week and 8 mg/d thereafter. Patients
      completed 3-day bladder diaries and the Overactive Bladder Questionnaire at
      baseline and week 12. Pooled data for changes from baseline to week 12 in
      winsorized UUI episodes, micturitions, and urgency episodes per 24 hours and
      Overactive Bladder Questionnaire Symptom Bother and health-related quality of
      life scores were analyzed posthoc using a regression model that selects outcome
      predictors from baseline values and patient characteristics while retaining
      baseline values and treatment, with stepwise inclusion of significant covariates
      and assessment of treatment interactions. Logistic regression was used for
      analysis of diary-dry rates. RESULTS: Younger age, lack of previous
      antimuscarinic treatment, shorter duration of OAB diagnosis, and female gender
      were common predictors of larger changes in outcomes from baseline to week 12.
      Baseline measures often interacted with treatment, such that poorer baseline
      outcomes were predictive of larger treatment differences. Longer duration since
      OAB diagnosis predicted greater treatment differences for UUI episodes and in
      diary-dry rate, and increased age predicted greater treatment differences for
      micturitions. CONCLUSION: Symptom severity and duration, age, gender, and
      previous antimuscarinic pharmacotherapy impact the response to antimuscarinic
      treatment.

PMID- 24582120
TI  - Modified retroperitoneoscopic renal pedicle lymphatic disconnection for
      intractable chyluria.
AB  - INTRODUCTION: To describe a modified retroperitoneoscopic renal pedicle lymphatic
      disconnection (MRRPLD) and to compare the efficacy and safety of MRRPLD with
      traditional retroperitoneoscopic renal pedicle lymphatic disconnection (RRPLD).
      TECHNICAL CONSIDERATIONS: From September 2008 to July 2012, RRPLD and MRRPLD were
      performed respectively on 18 and 14 patients at our center. Comparison was
      conducted including operative time, intraoperative blood loss, postoperative time
      of bed rest, hospital stay, postoperative urine chyle test, and complications.
      All operations were completed without conversion to open surgery. The mean
      operative time, intraoperative blood loss, postoperative time of bed rest, and
      hospital stay from MRRPLD group were all decreased compared with data from RRPLD
      group. There was significant difference in operative time, postoperative time of
      bed rest, and hospital stay (P <.05). Complications occurred only in 1 patient
      receiving RRPLD. Chyluria disappeared in all patients after the operation. No
      recurrence was observed during the follow-up. CONCLUSION: MRRPLD has a good
      effect and safety for chyluria. It is a simpler, more minimally invasive, and
      more economic surgical therapy compared with traditional RRPLD.

PMID- 24582121
TI  - Monti's principle in the treatment of congenital uterovesical fistula.
AB  - Congenital uterovesical fistula is rare and generally associated with genital
      tract abnormalities derived from mullerian ducts or urogenital sinus. Management
      is usually challenging, and it involves vaginal reconstruction. A 15-year-old
      female patient presented with a 2-year history of cyclical hematuria.
      Investigation revealed a bicornuate uterus and complete vaginal agenesis
      associated with congenital uterovesical fistula. The fistula was repaired, and a
      neovagina was created using Monti's technique. Postoperative recovery was
      uneventful with normal voiding and initiation of regular menstruation through the
      neovagina. We discuss the options of vaginal reconstruction and stress the
      advantages of the technique used in this case. 

PMID- 24582122
TI  - Risk-based surveillance of antimicrobial residues in pigs--identification of
      potential risk indicators.
AB  - Around 20,000 samples are analysed each year for the presence of antibacterial
      residues in Danish finisher pigs, and between zero and five samples are detected
      positive above the maximum residue level (MRL). The intention was to develop a
      risk-based surveillance programme involving fewer samples while ensuring equal
      sensitivity. Therefore, risk indicators were searched for. Data were obtained
      from the Danish slaughterhouse database covering the period from July 2010 to
      December 2012. Residues were found or suspected in 17 incidents. In nine of
      these, the farmer had called in to prevent the pigs from being slaughtered.
      Hence, eight suspect cases were found through the surveillance programme, and two
      of these were above MRL. For these eight case herds, the number of pigs
      slaughtered and the number in which each of the following lesions were found were
      included in a statistical analysis: chronic pleuritis, tail bite, chronic
      pericarditis, chronic pneumonia, chronic peritonitis, osteomyelitis, abscess in
      hindquarters, abscess in leg/toe and abscess in forequarters. Only chronic
      pleuritis was associated with the presence of residues. Next, data from all herds
      delivering pigs for slaughter to the same abattoir were included covering a 3
      month period prior to the residue finding. The prevalence of chronic pleuritis
      was on average 1.7 times higher in the eight case herds compared to all other
      herds. In two herds, the prevalence was significantly higher (P<=0.05), and in
      one herd substantially higher, but only borderline significant (P=0.1). In the
      remaining herds, the prevalence did not differ from the other herds delivering
      pigs to the abattoir. This indicates that chronic pleuritis might be considered
      as a risk indicator for use in surveillance. Other risk indicators/factors -
      reported in the cases where the farmers called in - were inadequate marking of
      treated animals and incorrect use of medication dispensers. These factors are not
      suited for use in surveillance and should be dealt with otherwise. 

PMID- 24582123
TI  - [Typical febrile seizures in an immigrant patient].

PMID- 24582124
TI  - [Recurrent staphylococcal scalded skin syndrome. Is there something else?].

PMID- 24582125
TI  - [Diaphragmatic defect, congenital heart disease, agonadism: a new case of PAGOD
      syndrome].

PMID- 24582126
TI  - [Spartium junceum (Spanish broom) poisoning].

PMID- 24582127
TI  - [Adverse reactions to human papillomavirus vaccine in the Valencian Community
      (2007-2011)].
AB  - INTRODUCTION: In 2009, two cases of seizures in adolescents following
      quadrivalent human papillomavirus vaccine (qHPV) administration, generated
      important media attention, and adversely affected public trust in this vaccine.
      Our objectives were to describe suspected adverse reactions (SARs) reported to
      the Pharmacovigilance Centre in the Valencian Community (PCVC) after
      administration of HPV vaccine, and to compare reporting rates of syncope and
      seizures following this vaccine with those of other vaccines administered to
      girls aged 13-15 years. MATERIAL AND METHODS: Descriptive study of SARs reported
      following this vaccine to the PCVC between 2007 and 2011. RESULTS: The clinical
      symptoms most frequently reported were dizziness, headache, and syncope.
      Reporting rates of syncope or loss of consciousness and seizures with qHPV
      vaccine were 17 and 3.2 per 100,000 doses administered, respectively, and 15 and
      1.6 for syncope or loss of consciousness and syncopal seizures occurred on the
      day of vaccination. The reporting rates of syncope or loss of consciousness and
      seizures were 6.4 and 0.4, for the other vaccines. CONCLUSIONS: Consistent with
      the media attention generated, and with results from other studies, the reporting
      rates of syncope or loss of consciousness and seizures were higher for the HPV
      vaccine than for other vaccines given in adolescence. Nevertheless, the overall
      information obtained on SARs following the qHPV vaccine suggests a good safety
      profile.

PMID- 24582128
TI  - [Complicated subcutaneous fat necrosis after hypothermia treatment for severe
      hypoxic-ischemic encephalopathy].

PMID- 24582129
TI  - [Type 1 polyglandular autoimmune syndrome associated with C322fsx372 mutation].
AB  - Polyglandular autoimmune syndromes are rare diseases based on autoimmune
      mechanisms in which endocrine and non-endocrine disorders coexist. In type 1 the
      characteristic manifestations are chronic mucocutaneous candidiasis,
      hypoparathyroidism and adrenal insufficiency. A case is presented of a patient
      with typical clinical sequence, along with other changes, and in whom a mutation
      in homozygosis, C322fsX372, was detected after performing a molecular analysis of
      autoimmunity regulator gene (AIRE). Inheritance is autosomal recessive,
      associated with mutations in the AIRE gene, which encodes a protein involved in
      autoimmunity and immunodeficiency. For diagnosis, At least two of the three major
      clinical manifestations are required for a diagnosis. However, only one of them
      is necessary in the study of relatives of affected patients. These syndromes must
      be diagnosed early, given their high morbidity and mortality. Every manifestation
      needs to be treated, in order to maintain the quality of life.

PMID- 24582130
TI  - Intra-articular corticosteroids under threat in Thoroughbred racehorse practice.

PMID- 24582131
TI  - Does intraoperative low arterial partial pressure of oxygen increase the risk of
      surgical site infection following emergency exploratory laparotomy in horses?
AB  - Decreased tissue oxygenation is a critical factor in the development of wound
      infection as neutrophil mediated oxidative killing is an essential mechanism
      against surgical pathogens. The objective of this prospective case series was to
      assess the impact of intraoperative arterial partial pressure of oxygen (PaO2) on
      surgical site infection (SSI) in horses undergoing emergency exploratory
      laparotomy for acute gastrointestinal disease. The anaesthetic and antibiotic
      protocol was standardised. Demographic data, surgical potential risk factors and
      PaO2, obtained 1h after induction of anaesthesia were recorded. Surgical wounds
      were assessed daily for infection during hospitalisation and follow up
      information was obtained after discharge. A total of 84 adult horses were
      included. SSI developed in 34 (40.4%) horses. Multivariate logistic regression
      showed that PaO2, anaesthetic time and subcutaneous suture material were
      predictors of SSI (AUC=0.76, sensitivity=71%, specificity=65%). The use of
      polyglycolic acid sutures increased the risk and horses with a PaO2 value < 80 mm
      Hg [10.6 kPa] and anaesthetic time >2h had the highest risk of developing SSI
      (OR=9.01; 95% CI 2.28-35.64). The results of this study confirm the hypothesis
      that low intraoperative PaO2 contributes to the development of SSI following
      colic surgery.

PMID- 24582132
TI  - Versican expression in myoepithelial cells from carcinomas in canine mixed
      mammary tumors.
AB  - The matrix of canine mixed mammary tumors (CMMTs) consists of proliferating
      spindle cells of possible myoepithelial origin, as well as myxomatous tissue,
      cartilage matrix and/or bone. Among the multiple components of this tumor
      extracellular matrix, versican probably plays a prominent role due to its
      importance in tumor progression, cell proliferation and differentiation. However,
      there are few data related to a possible association between versican expression
      and the state of myoepithelial cell differentiation in CMMTs. Using
      immunohistochemistry and histochemistry, the objective of this study was to
      evaluate the expression of versican, sulfated proteoglycans and
      mucopolysaccharides in myoepithelial cells at different stages of differentiation
      and to explore a potential relationship with p63 and alpha-smooth muscle actin
      (SMA) expression. A significant difference in versican expression was observed
      among the different stages of myoepithelial cell differentiation with an inverse
      correlation between versican and p63/SMA expression. These results suggest that
      at an early stage of proliferation, myoepithelial cells acquire a phenotype
      consistent with a role in chondrogenesis. Moreover, myoepithelial cells showed an
      affinity for safranin and periodic acid-Schiff staining at different stages of
      proliferation supporting the myoepithelial origin of spindle cells from CMMTs. 

PMID- 24582133
TI  - Transition from a fixed implant dental prosthesis to an implant overdenture in an
      edentulous patient: a clinical report.
AB  - The lack of planning before implant placement and restoration in edentulous
      patients can lead to a number of problems. Prosthodontists are often faced with
      the challenge of re-treating patients who have only recently been treated.
      Although many reports discuss retreatment by fabricating all new prosthetic
      components, few discuss salvaging parts of the patient's existing prosthesis.
      This report details the treatment of an edentulous patient who presented with an
      implant-retained fixed dental prosthesis in the maxillary arch and no opposing
      prosthesis. The transition from an implant-retained fixed dental prosthesis to a
      removable implant- and tissue-supported overdenture that uses the patient's
      existing computer-aided design/computer-aided manufacturing milled titanium
      substructure is described. 

PMID- 24582134
TI  - Antifungal efficacy of thymol, carvacrol, eugenol and menthol as alternative
      agents to control the growth of food-relevant fungi.
AB  - OBJECTIVE: This work is an attempt to examine the antifungal activity of thymol,
      carvacrol, eugenol and menthol against 11 food-decaying fungi. METHODS: The
      susceptibility test for the compounds was carried out in terms of minimum
      inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) using
      microdilution method in 96 multi-well microtiter plates. RESULTS: Results
      indicated that all compounds were effective to varying extents against various
      fungal isolates, with the highest efficacy displayed by carvacrol (mean MIC
      value: 154.5 MUg/mL) (P<0.05). The incorporation of increased concentrations of
      all compounds to the media led to progressive and significant reduction in growth
      for all fungi. The most potent inhibitory activity of thymol, carvacrol, eugenol
      and menthol was found for Cladosporium spp. (MIC: 100 MUg/mL), Aspergillus spp.
      (MIC: 100 MUg/mL), Cladosporium spp. (MIC: 350 MUg/mL), and Aspergillus spp. and
      Cladosporium spp. (MIC: 125 MUg/mL), respectively. CONCLUSION: Thus, the
      application of these herbal components could be considered as a good alternatives
      to inhibit fungal growth and to reduce the use of synthetic fungicides.

PMID- 24582135
TI  - Patients' knowledge of oral and maxillofacial surgery terminology.

PMID- 24582136
TI  - Body dysmorphic disorder and psychological distress in orthognathic surgery
      patients.
AB  - PURPOSE: Body dysmorphic disorder (BDD) is a distressing condition involving
      preoccupation with an imagined or exaggerated deformity. The purpose of our study
      was to investigate the presence of BDD and its comorbidity with anxiety,
      depression, and obsessive-compulsive disorder (OCD) in patients undergoing
      orthognathic surgery (OS). MATERIALS AND METHODS: The present prospective study
      included 99 patients from the outpatient oral and maxillofacial surgery clinic at
      Stanford University who requested OS. The incidence of BDD, depression, anxiety,
      and OCD was assessed preoperatively using validated self-report measures. To
      determine the prevalence of Axis I psychological symptoms among patients, the
      descriptive and bivariate statistics were computed. P < .05 was considered
      significant. RESULTS: In our sample, 13 patients (13%) screened positive for BDD.
      We did not find any significant correlations between the presence of BDD and
      gender, race, age, or marital status. Depressive symptoms were reported by 42% of
      the patients, OCD symptoms by 29%, and mild, moderate, and severe anxiety by 14%,
      5%, and 4%, respectively. Using Spearman correlations, we found significant
      correlations between BDD and anxiety, depression, and OCD (P < .01). CONCLUSIONS:
      The results of the present study suggest that the rates of BDD, depression,
      anxiety, and OCD are high in patients undergoing OS. Furthermore, we found a
      strong correlation between BDD and anxiety, OCD, and depression in these
      patients. Future studies are necessary to determine the postoperative changes in
      these psychological disorders and whether these changes are affected by having
      positive BDD screening results at baseline.

PMID- 24582137
TI  - Effects of lead exposure on the expression of amyloid beta and phosphorylated tau
      proteins in the C57BL/6 mouse hippocampus at different life stages.
AB  - The objective of this study was to investigate the effects of lead exposure on
      spatial learning and memory capacity and the expression of amyloid beta and
      phosphorylated tau proteins in the mouse hippocampus. A total of 24 adult C57BL/6
      mice (12 of each sex) were mated at a 1:1 ratio. After delivery, the litters were
      normalised to 6 pups per litter. During the lactation period, the pups were
      randomly separated into four groups: control, early exposure, late exposure, or
      long-term exposure. These groups were not exposed to lead, exposed to lead from
      birth to week 24, exposed to lead from week 24 to week 48, or exposed to lead
      from birth to 48 weeks of age, respectively. Lead exposure was induced by
      providing Pb-contaminated drinking water at a concentration of 0.1%. All of the
      pups were fed until 72 weeks of age, at which time their spatial learning and
      memory capacity was evaluated via the Morris water maze test. Then, the lead
      levels in their blood and hippocampus were measured via graphite furnace atomic
      absorption spectrometry. The protein expression of amyloid beta and
      phosphorylated tau in the hippocampus was detected via Western blot. The results
      revealed that the hippocampal and blood lead levels were significantly higher in
      all of the groups exposed to lead than the control group (P<0.05). The spatial
      learning and memory performances of the lead-exposed groups were much poorer than
      those of the control group (P<0.05). The expression levels of amyloid beta and
      phosphorylated tau proteins were increased in the lead-exposed groups compared to
      the control group (P<0.05). The enhanced expressions of amyloid beta and
      phosphorylated tau proteins might contribute to the impairment in spatial
      learning and memory in the lead-exposed mice. 

PMID- 24582138
TI  - Differences in the redox status of human visceral and subcutaneous adipose
      tissues--relationships to obesity and metabolic risk.
AB  - OBJECTIVE: Metabolic homeostasis depends on adipocyte metabolic
      responses/processes, most of which are redox-regulated. Besides, visceral and
      subcutaneous adipose tissues (VAT and SAT, respectively) differ metabolically and
      in their contribution to metabolic complications, but their redox characteristics
      in humans are still unknown. To understand the molecular mechanisms of metabolic
      syndrome development, we analysed the redox characteristics of VAT and SAT in
      groups with various body weights and metabolic risks. MATERIAL AND METHODS: Fifty
      premenopausal women were classified according to body mass index into normal
      weight and obese groups, and these groups were further sub-classified into
      metabolically healthy and metabolically obese ("at risk") based on the
      homeostasis model assessment of insulin resistance (HOMA-IR) index and the
      triglyceride, total-, LDL- and HDL-cholesterol levels. Antioxidant components,
      NADPH oxidase protein and 4-hydroxynonenal (4-HNE) levels were analysed in VAT
      and SAT. RESULTS: Compared with the SAT, the VAT showed a higher basal level of
      glutathione (GSH) and GSH-dependent enzyme activities. Compared with the
      metabolically healthy normal-weight controls, the obese groups of women showed
      lower GSH levels in both depots. However, in these groups, additional
      prooxidative changes (increased NADPH oxidase and 4-HNE and decreased levels of
      SOD and/or CAT) were observed only in VAT. CONCLUSIONS: Because of the critical
      role of thiol-redox homeostasis in lipogenesis, interdepot-differences in the GSH
      dependent antioxidant part may be connected to the higher metabolic activity
      found in VAT. Analogously, the lower GSH levels that occur during obesity and the
      corresponding additional redox imbalance may be signs of VAT metabolic
      dysfunction that underlie the subsequent metabolic impairment.

PMID- 24582139
TI  - Potential epigenetic dysregulation of genes associated with MODY and type 2
      diabetes in humans exposed to a diabetic intrauterine environment: an analysis of
      genome-wide DNA methylation.
AB  - OBJECTIVE: The aim of this study is to investigate the potential role of DNA
      methylation in mediating the increased risk of developing type 2 diabetes in
      offspring of mothers who had diabetes during pregnancy. MATERIALS AND METHODS:
      Peripheral blood leukocytes were collected from non-diabetic Pima Indians who
      were either offspring of diabetic mothers (ODM; n=14) or offspring of nondiabetic
      mothers (ONDM; n=14). The two groups were matched for age, sex, age of mother,
      and fraction of Pima ethnicity. Differentially methylated regions were determined
      using a MeDIP-chip assay on an Affymetrix Human Tiling 2.0R Array. Data were
      analyzed using the model based analysis of tiling arrays (MAT) algorithm, and
      4883 regions overlapping with putative promoters, were identified as
      differentially methylated, having met an empirically derived threshold (nominal
      p<0.0077). The list of genes with differentially methylated promoters was
      subjected to KEGG pathway analysis to determine canonical metabolic pathways
      enriched by these genes. RESULTS: Pathway analysis of genes with differentially
      methylated promoters identified the top 3 enriched pathways as maturity onset
      diabetes of the young (MODY), type 2 diabetes, and Notch signaling. Several genes
      in these pathways are known to affect pancreatic development and insulin
      secretion. CONCLUSIONS: These findings support the hypothesis that epigenetic
      changes may increase the risk of type 2 diabetes via an effect on beta-cell
      function in the offspring of mothers with diabetes during pregnancy.

PMID- 24582140
TI  - Butterfly vertebra.

PMID- 24582141
TI  - Physical fitness in children with developmental coordination disorder:
      measurement matters.
AB  - Children with Developmental Coordination Disorder (DCD) experience considerable
      difficulties coordinating and controlling their body movements during functional
      motor tasks. Thus, it is not surprising that children with DCD do not perform
      well on tests of physical fitness. The aim of this study was to determine whether
      deficits in motor coordination influence the ability of children with DCD to
      perform adequately on physical fitness tests. A case-control study design was
      used to compare the performance of children with DCD (n=70, 36 boys, mean age=8 y
      1 mo) and Typically Developing (TD) children (n=70, 35 boys, mean age=7 y 9 mo)
      on measures of isometric strength (hand-held dynamometry), functional strength,
      i.e. explosive power and muscular endurance (Functional Strength Measurement),
      aerobic capacity (20 m Shuttle Run Test) and anaerobic muscle capacity, i.e.
      muscle power (Muscle Power Sprint Test). Results show that children with DCD were
      able to generate similar isometric forces compared to TD children in isometric
      break tests, but were significantly weaker in three-point grip strength.
      Performance on functional strength items requiring more isolated explosive
      movement of the upper extremities, showed no significant difference between
      groups while items requiring muscle endurance (repetitions in 30s) and items
      requiring whole body explosive movement were all significantly different. Aerobic
      capacity was lower for children with DCD whereas anaerobic performance during the
      sprint test was not. Our findings suggest that poor physical fitness performance
      in children with DCD may be partly due to poor timing and coordination of
      repetitive movements.

PMID- 24582142
TI  - Rett syndrome: a preliminary analysis of stereotypy, stress, and negative affect.
AB  - Rett syndrome (RTT) is a neurodevelopmental disorder primarily affecting females.
      It is characterized by apparently normative development of motor and
      communicative abilities followed by deterioration in these domains. Stereotypic
      hand movements are one of the core diagnostic criteria for RTT. There is some
      anecdotal but limited scientific evidence that changes in hand stereotypy may be
      a sign of increased anxiety or arousal (i.e., a 'stress response') in RTT.
      Understanding stress responsivity is difficult in RTT because almost all
      individuals are nonverbal or otherwise severely communicatively impaired. This
      study used direct behavioral observation to quantify and compare the frequency of
      hand stereotypy and signs of negative affect during presumed periods of high and
      low stress associated with functional analysis conditions (negative reinforcement
      ['escape'] and control ['free play'], respectively) for 5 females with RTT (mean
      age=17.8; range 4-47). Negative affect was more likely to occur during negative
      reinforcement ('stress') conditions for each participant whereas hand
      stereotypies did not differ across conditions for any of the participants.
      Although preliminary, the results suggest that hand stereotypy may not be a valid
      behavioral 'stress-response' indicator in females with RTT. Alternatively, the
      approach we used may have been limited and not sufficient to evoke a stress
      response. Either way, more work with direct relevance to improving our
      understanding of hand stereotypy and anxiety in RTT in relation to social context
      appears warranted. 

PMID- 24582143
TI  - Altered immune responses in patients with chronic mucocutaneous candidiasis.
AB  - OBJECTIVE: The purpose of this study was to investigate the lymphocyte
      transformation responses and cytokine secretion of peripheral blood mononuclear
      cells (PBMC) from patients with chronic mucocutaneous candidiasis (CMC). METHODS:
      Phytohaemagglutinin (PHA) mitogen and Candida albicans (C. albicans) antigen
      proliferation assays were performed by culturing PBMCs in RPMI 1640. The levels
      of interleukin (IL)-2, IL-10, IL-17 and interferon (IFN)-gamma present in the
      supernatant of cultures were determined using enzyme-linked immunosorbent assay
      (ELISA). RESULTS: The results showed that most patients (92.3%) had a low
      proliferative response to C. albicans antigens and PHA. PBMCs from CMC patients
      produced lower levels of T (h)-1 cytokines IL-2 (78.5+/-59.8 pg/mL) and IFN-gamma
      (115.1+/-43.3 pg/mL) in response to Candida antigens when compared to controls
      (Il-2: 177+/-103.6 pg/mL; IFN-gamma: 330.3+/-21.6 pg/mL) (P<0.05). Conversely, we
      observed a partial enhancement of IL-10 in the patients (213.7+/-86.1 pg/mL).
      Production of IL-17 indicated no significant differences between patients and
      controls when stimulated by Candida antigens (21.5+/-8.6 pg/mL versus 32.4+/-12.2
      pg/mL) and PHA (27.7+/-11.5 pg/mL versus 36.2+/-9.1 pg/mL), respectively.
      CONCLUSION: These findings suggest that Candida antigens trigger a Th2 instead of
      Th1 cytokine response in patients with CMC. For better understanding, further
      studies require on a larger number of patients into the future.

PMID- 24582144
TI  - The course of health-related quality of life in head and neck cancer patients
      treated with chemoradiation: a prospective cohort study.
AB  - BACKGROUND AND PURPOSE: To evaluate the course of health-related quality of life
      (HRQOL) from diagnosis to 2 years follow-up in patients with head and neck cancer
      (HNSCC) treated with chemoradiation (CRT). MATERIALS AND METHODS: 164 patients
      completed the EORTC QLQ-C30 and QLQ-H&N35 questionnaires 1 week before and 6
      weeks and 6, 12, 18, and 24 months after CRT. Patients were compared to a
      reference group. A linear mixed-model analysis was used to assess changes in
      HRQOL over time, and whether this was associated with age, gender, comorbidity,
      and tumor sublocation. RESULTS: Significant differences for the majority of HRQOL
      scales were observed between patient and reference group at baseline, and follow
      up. The course of HRQOL was different for survivors compared to non-survivors. In
      survivors, improvement over time was observed (in global quality of life,
      physical, role, and social function, fatigue, pain, swallowing, speech, social
      eating, and social contacts), while in non-survivors the pattern over time was
      either no changes in HRQOL or a deterioration (in physical function, social
      eating and contacts). In both survivors and non-survivors, emotional functioning
      improved after treatment, but deteriorated in the longer term. Patients with
      comorbidity reported worse physical function, and patients with
      oral/oropharyngeal cancer (compared to hypopharyngeal/laryngeal cancer) reported
      more oral pain and sexual problems, but fewer speech problems. CONCLUSIONS: The
      course of HRQOL of HNSCC patients during the first 2 years after CRT is different
      for survivors compared to non-survivors and is associated with comorbidity and
      tumor subsite.

PMID- 24582145
TI  - The BBX family of plant transcription factors.
AB  - The B-box (BBX) proteins are a class of zinc-finger transcription factors
      containing a B-box domain with one or two B-box motifs, and sometimes also
      feature a CCT (CONSTANS, CO-like, and TOC1) domain. BBX proteins are key factors
      in regulatory networks controlling growth and developmental processes that
      include seedling photomorphogenesis, photoperiodic regulation of flowering, shade
      avoidance, and responses to biotic and abiotic stresses. In this review we
      discuss the functions of BBX proteins and the role of B-box motif in mediating
      transcriptional regulation and protein-protein interaction in plant signaling. In
      addition, we provide novel insights into the molecular mechanisms of their action
      and the evolutionary significance of their functional divergence. 

PMID- 24582146
TI  - Innovations in hip fracture care: a comparison of geriatric fracture centers.

PMID- 24582147
TI  - FTIR analysis of the metabolomic stress response induced by N-alkyltropinium
      bromide surfactants in the yeasts Saccharomyces cerevisiae and Candida albicans.
AB  - The activity of surfactants against fungal cells has been studied less than
      against bacteria, although the medical and industrial importance of the former is
      of paramount importance. In this paper the surfactant biocidal effect was
      measured in the yeasts Saccharomyces cerevisiae and Candida albicans with a
      previously described FTIR bioassay which estimates the stress level as function
      of the FTIR spectra variation of the cells upon exposition to the chemicals. N
      tetradecyltropinium bromide was chosen as stressing agent on the basis of
      previous preliminary study demonstrating its ability to kill prokaryotic and
      especially eukaryotic cells at concentration around or over the critical micellar
      concentration (c.m.c.). Here we show that this surfactant is able to inactivate
      S. cerevisiae cells at 0.4mM and C. albicans cells at 0.6mM after 1h exposition.
      FTIR analysis revealed that the surfactant induced metabolomics reactions of S.
      cerevisiae cells in the regions of amides (W2) and fatty acids (W1). In the same
      way C. albicans cells showed the maximum stress response in amides (W2) and mixed
      (W3) regions. Variations of the hydrophobic tail of this surfactant produced a
      reduced level of cell stress with both the 12C and 16C variants; although these
      two compounds were more effective in inducing cell mortality in S. cerevisiae but
      not in C. albicans. In conclusion, this paper has shown that, for this
      surfactant, the n-alkyl chain must vary between 12C and 16C and that the
      hydrophilic head size is not as critical as the tail length.

PMID- 24582148
TI  - Biological properties of a DHA-containing structured phospholipid (AceDoPC) to
      target the brain.
AB  - 1-acetyl,2-docosahexaenoyl-glycerophosphocholine (AceDoPC) has been made to
      prevent docosahexaenoyl (DHA) to move to the sn-1 position as it rapidly does
      when present in 1-lyso,2-docosahexaenoyl-GPC (lysoPC-DHA), an efficient DHA
      transporter to the brain. When incubated with human blood, AceDoPC behaves closer
      to lysoPC-DHA than PC-DHA in terms of binding to plasma albumin and lipoproteins,
      and DHA incorporation into platelets and red cells. In addition, AceDoPC prevents
      more efficiently the deleterious effects of the experimental stroke in rats than
      does unesterified DHA. Also, AceDoPC inhibits platelet-activating factor-induced
      human blood platelet aggregation. Overall, AceDoPC might act as an efficient DHA
      transporter to the brain, and as a neuro-protective agent by itself. 

PMID- 24582149
TI  - Therapist characteristics that predict the outcome of multipatient psychotherapy:
      systematic review of empirical studies.
AB  - We defined multipatient psychotherapy as the set of psychotherapeutic techniques
      applied with more than one patient in the room. Assumptions of what makes a
      psychotherapist effective guide training programmes but may not be supported by
      evidence. We need to identify the empirical data on what makes a multipatient
      psychotherapist effective. We undertook the systematic review of empirical
      studies which correlate therapist characteristics with measurable patient outcome
      in multipatient psychotherapy. We found that the scientific literature on the
      topic is broad and heterogeneous in scope, studying demographic, professional and
      psychosocial characteristics of the therapists, but is poor in quality. The most
      solid results are that ethnic matching improves the outcome of family therapy
      with drug abusing adolescents in some ethnic minorities and that therapist
      knowledge patterns affect patient satisfaction. We concluded that the therapist
      characteristics that affect clinical outcome seem to be internal to the therapist
      and depend on the patient treated. 

PMID- 24582150
TI  - Metabolic profiling study of early and late recurrence of hepatocellular
      carcinoma based on liquid chromatography-mass spectrometry.
AB  - The objectives of this pilot study were to predict early postoperative recurrence
      in hepatocellular carcinoma (HCC) patients based on metabolic features and to
      explore the related metabolic disturbances. Liquid chromatography-mass
      spectrometry-based metabolic profiling was performed on the plasma of 18 late
      recurrent and 22 early recurrent HCC patients. Metabolic differences were found
      to be related to amino acid, bile acid, cholesterol, fatty acid, phospholipid and
      carbohydrate metabolism. Bile acids, steroids and fatty acids showed significant
      variation in the early recurrent HCC group compared to the late recurrence group.
      Decreased levels of polyunsaturated eicosapentaenoic acid, docosahexaenoic acid
      and linolenic acid were found to be specific metabolic features for early
      recurrence. With the combination of methionine, GCDCA and cholesterol sulfate,
      85% of the early recurrent HCCs can be predicted correctly with the corresponding
      area under the curve (AUC) equal to 0.95 in the training set, and 80% of the
      early recurrent HCCs can be predicted correctly with the corresponding AUC equal
      to 0.91 in the test set. 

PMID- 24582151
TI  - Chiral amino acid analysis of Japanese traditional Kurozu and the developmental
      changes during earthenware jar fermentation processes.
AB  - Enantioselective amino acid metabolome analysis of the Japanese traditional black
      vinegars (amber rice vinegar, Kurozu) was performed using two-dimensional high
      performance liquid chromatography combining a microbore-monolithic ODS column and
      narrowbore-enantioselective columns. d-Amino acids, the enantiomers of widely
      observed l-amino acids, are currently paid attention as novel physiologically
      active substances, and the foodstuffs and beverages containing high amounts of d
      amino acids are the subjects of interest. In the present study, the amino acid
      enantiomers were determined by two-dimensional HPLC techniques after pre-column
      fluorescence derivatization with 4-fluoro-7-nitro-2,1,3-benzoxadiazole. In the
      first dimension, the amino acid enantiomers are separated as their d plus l
      mixtures by the reversed-phase mode, then the d-amino acids and their l
      counterparts are separately determined in the second dimension by the
      enantioselective columns. As a result, large amounts of d-Ala (800-4000nmol/mL),
      d-Asp (200-400nmol/mL) and d-Glu (150-500nmol/mL) were observed in some of the
      traditionally produced Kurozu vinegars. Relatively large or small amounts of d
      Ser (50-100nmol/mL), d-Leu (10-50nmol/mL) and d-allo-Ile (less than 20nmol/mL)
      were also present in these samples. Developmental changes in the d-amino acid
      amounts during the fermentation and aging processes have also been investigated. 

PMID- 24582152
TI  - Long-term predictors of impaired fasting glucose and type 2 diabetes in subjects
      with family history of type 2 diabetes: a 12-years follow-up of the Brisighella
      Heart Study historical cohort.
AB  - AIM: To identify and quantify the role of different risk factors in the long-term
      development of IFG and T2DM in a rural Italian population sample with family
      history of T2DM. METHODS: We selected a sample of 1271 adult subjects from among
      those 1851 consecutively visited during four consecutive Brisighella Heart Study
      surveys (1996-2008), then selecting those ones with a family history of T2DM.
      Thus, we obtained a final sample including 545 subjects and for which a full
      clinical and ematochemistry data set was available. RESULTS: The Cox-regression
      model better predicting the incident IFG and T2DM included age, gender, FPG, TG
      and SUA. The model best predicting the incident IFG status alone (without T2DM)
      is very similar to that predicting both IFG and T2DM, including the same
      predictors. Finally, the model best predicting T2DM (excluding IFG) simply
      includes FPG, BMI and ALT/AST ratio. Repeating the Cox-regression analysis using
      BMI as a covariate, TG appears to be also a significant predictor of T2DM (HR
      1.018 95% CI 1.009-1.041, p=0.013). CONCLUSION: In a sample of subjects with a
      family history of diabetes the best long-term predictors of IFG are age, gender,
      FPG, TG and SUA, while those of T2DM are FPG and BMI.

PMID- 24582156
TI  - Advances in the development of common noise assessment methods in Europe: The
      CNOSSOS-EU framework for strategic environmental noise mapping.
AB  - The Environmental Noise Directive (2002/49/EC) requires EU Member States to
      determine the exposure to environmental noise through strategic noise mapping and
      to elaborate action plans in order to reduce noise pollution, where necessary. A
      common framework for noise assessment methods (CNOSSOS-EU) has been developed by
      the European Commission in co-operation with the EU Member States to be applied
      for strategic noise mapping as required by the Environment Noise Directive
      (2002/49/EC). CNOSSOS-EU represents a harmonised and coherent approach to assess
      noise levels from the main sources of noise (road traffic, railway traffic,
      aircraft and industrial) across Europe. This paper outlines the process behind
      the development of CNOSSOS-EU and the parts of the CNOSSOS-EU core methodological
      framework which were developed during phase A of the CNOSSOS-EU process (2010
      2012), whilst focusing on the main scientific and technical issues that were
      addressed, and the implementation challenges that are being faced before it can
      become fully operational in the EU MS. 

PMID- 24582157
TI  - Support for partial lesions of the flexor tendons of the fingers: a retrospective
      study of 36 cases.
AB  - The treatment of traumatic partial injuries of the flexor tendons of the fingers
      is seldom published. The only published clinical series states that the
      therapeutic approach depends on the existence or absence of a preoperative
      trigger. We hypothesized that the therapeutic attitude mainly depends on the
      percentage of the injured cross-section. Our retrospective series included 36
      partial lesions of 31 fingers in 29 patients. The average age was 42 years, there
      were 19 men. We noted 8 lesions in zones I, 21 in zone II and 2 in zone III. The
      average percentage of the injured cross-section was 35% and ranged from 10% to
      90%. If the lesion was less than 50% (29 tendons), a tangential resection was
      performed. If the lesion exceeded 50% (seven tendons), a direct suture was
      performed, supplemented by a running suture. At a follow-up of 34 months, the
      average pain on a visual analogue scale was 0.7. The average percentage of
      strength compared to the contralateral side was 93%. The Quick DASH score was
      6.2. The range of motion averaged 214 degrees  with extremes ranging from 90
      degrees  to 260 degrees . We observed no cases of hypertrophic callus, neither
      through the MRI nor through the ultrasonography. Complications such as trigger
      finger, pseudoblocage or rupture were not observed. Based on our results, in case
      of partial injury of a flexor tendon, we propose to perform a tangential
      resection in cross-section lesions up to 50%, and a suture for those which
      exceeded 50%.

PMID- 24582158
TI  - [Treatment for a chronic proximal interphalangeal fracture-dislocation with hemi
      hamate arthroplasty].
AB  - Fracture-dislocations of the proximal interphalangeal (PIP) joint are complex and
      challenging to manage once they become chronic. We report a case of PIP joint
      fracture-dislocation treated by hemi-hamate arthroplasty. An 18-year-old male
      polytrauma patient presented with a neglected PIP joint fracture-dislocation in
      the third finger of the left hand. After four months of follow-up, he remained
      disabled due to clinodactyly and stiffness. After performing a cadaver study to
      evaluate the feasibility of grafting, we resurfaced the bone-cartilage defect
      with a hemi-hamate arthroplasty. The range of motion at the last follow-up was 65
      degrees  without pain; the DASH score was 2.27. The patient was able to return to
      heavy manual labour work at 5 months postoperative. 

PMID- 24582159
TI  - Risk factors for total hip arthroplasty aseptic revision.
AB  - The purpose of this study was to evaluate patient, operative, implant, surgeon,
      and hospital factors associated with aseptic revision after primary THA in
      patients registered in a large US Total Joint Replacement Registry. A total of
      35,960 THAs registered from 4/2001-12/2010 were evaluated. The 8-year survival
      rate was 96.7% (95% CI 96.4%-97.0%). Females had a higher risk of aseptic
      revision than males. Hispanic and Asian patients had a lower risk of revision
      than white patients. Ceramic-on-ceramic, ceramic-on-conventional polyethylene,
      and metal-on-conventional polyethylene bearing surfaces had a higher risk of
      revision than metal-on-highly cross-linked polyethylene. Body mass index, health
      status, diabetes, diagnosis, fixation, approach, bilateral procedures, head size,
      surgeon fellowship training, surgeon and hospital volume were not revision risk
      factors. 

PMID- 24582160
TI  - Patellar denervation in total knee arthroplasty without patellar resurfacing and
      postoperative anterior knee pain: a meta-analysis of randomized controlled
      trials.
AB  - The aim of this meta-analysis was to investigate whether patellar denervation
      with electrocautery (PD) after total knee arthroplasty (TKA) could reduce the
      postoperative anterior knee pain (AKP). Five randomized controlled trials (RCTs)
      with 572 patients and 657 knees were eligible for this meta-analysis. Our results
      showed that PD was associated with less AKP, lower visual analogue scale (VAS),
      higher patellar scores and better knee function compared with no patellar
      denervation (NPD). Complications did not differ significantly between the two
      groups. The existing evidence indicates that PD may be a better approach, as it
      improves both anterior knee pain and knee function after TKA. Future multi-center
      randomized controlled studies with large sample sizes are required to verify the
      current findings.

PMID- 24582161
TI  - A systematic review of clinical outcomes and survivorship after total knee
      arthroplasty with a contemporary modular knee system.
AB  - A systematic review appraising the clinical performance and safety of the primary
      SIGMA modular knee system (DePuy-Synthes, Warsaw, Ind.) found 5 registry reports
      and 53 journal publications reporting survivorship or postoperative increase in
      Knee Society scores on 241632 primary SIGMA knee arthroplasties. Pooled data from
      national joint registries and clinical studies on primary SIGMA knee survivorship
      were comparable. Both were higher than for all other knees in 5 national joint
      registries up to 5 years. Compared with pooled data from 2 independent systematic
      reviews of primary non-SIGMA knees, the SIGMA system provided comparable
      postoperative changes in Knee Society knee score and a nonsignificant trend of
      higher postoperative changes in Knee Society function score. This finding
      suggests that this knee system provides excellent durable results. 

PMID- 24582162
TI  - Multidirectional global left ventricular systolic function in normal subjects and
      patients with hypertension: multicenter evaluation.
AB  - BACKGROUND: The aim of this multicenter study was to determine the normal ranges
      and the clinical relevance of multidirectional systolic parameters to evaluate
      global left ventricular (LV) systolic function. METHODS: Three hundred twenty
      three healthy adult subjects prospectively included at 10 centers and a cohort of
      310 patients with hypertension were analyzed. Multidirectional global LV systolic
      function was analyzed using two-dimensional speckle-tracking echocardiography by
      means of two indices: longitudinal-circumferential systolic index (the average of
      longitudinal and circumferential global systolic strain) and global systolic
      index (the average of longitudinal, circumferential, and radial global systolic
      strain). RESULTS: The ranges of values of the multidirectional systolic
      parameters in healthy subjects were -21.22 +/- 2.22% for longitudinal
      circumferential systolic index and 29.71 +/- 5.28% for global systolic index. In
      addition, the lowest expected values of these multidirectional indices were
      determined in this population (calculated as -1.96 SDs from the mean): -16.86%
      for longitudinal-circumferential systolic index and 19.36% for global systolic
      index. Concerning the clinical relevance of these measurements, these indices
      indicated the presence of subtle LV global systolic dysfunction in patients with
      hypertension, even though LV global longitudinal systolic strain and LV ejection
      fraction were normal. Moreover, in these patients, functional class (dyspnea [New
      York Heart Association classification]) was inversely related to both the
      longitudinal-circumferential index and the global systolic index. CONCLUSIONS: In
      the present multicenter study analyzing a large cohort of healthy subjects and
      patients with hypertension, the normal range and the clinical relevance of
      multidirectional systolic parameters to evaluate global LV systolic function have
      been determined.

PMID- 24582163
TI  - Normal ranges of right ventricular systolic and diastolic strain measures in
      children: a systematic review and meta-analysis.
AB  - BACKGROUND: Establishment of the range of normal values and associated variations
      of two-dimensional (2D) speckle-tracking echocardiography (STE)-derived right
      ventricular (RV) strain is a prerequisite for its routine clinical application in
      children. The objectives of this study were to perform a meta-analysis of normal
      ranges of RV longitudinal strain measurements derived by 2D STE in children and
      to identify confounders that may contribute to differences in reported measures.
      METHODS: A systematic review was conducted in PubMed, Embase, Scopus, the
      Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov. Search
      hedges were created to cover the concepts of pediatrics, STE, and the right heart
      ventricle. Two investigators independently identified and included studies if
      they reported the 2D STE-derived RV strain measure RV peak global longitudinal
      strain, peak global longitudinal systolic strain rate, peak global longitudinal
      early diastolic strain rate, peak global longitudinal late diastolic strain rate,
      or segmental longitudinal strain at the apical, middle, and basal ventricular
      levels in healthy children. Quality and reporting of the studies were assessed.
      The weighted mean was estimated using random effects with 95% confidence
      intervals (CIs), heterogeneity was assessed using Cochran's Q statistic and the
      inconsistency index (I(2)), and publication bias was evaluated using funnel plots
      and Egger's test. Effects of demographic, clinical, equipment, and software
      variables were assessed in a metaregression. RESULTS: The search identified 226
      children from 10 studies. The reported normal mean values of peak global
      longitudinal strain among the studies varied from -20.80% to -34.10% (mean, 
      29.03%; 95% CI, -31.52% to -26.54%), peak global longitudinal systolic strain
      rate varied from -1.30 to -2.40 sec(-1) (mean, -1.88 sec(-1); 95% CI, -2.10 to 
      1.59 sec(-1)), peak global longitudinal early diastolic strain rate ranged from
      1.7 to 2.69 sec(-1) (mean, 2.34 sec(-1); 95% CI, 2.00 to 2.67 sec(-1)), and peak
      global longitudinal late diastolic strain rate ranged from 1.00 to 1.30 sec(-1)
      (mean, 1.18 sec(-1); 95% CI, 1.04 to 1.33 sec(-1)). A significant base-to-apex
      segmental strain gradient (P < .05) was observed in the RV free wall. There was
      significant between-study heterogeneity and inconsistency (I(2) > 88% and P < .01
      for each strain measure), which was not explained by age, gender, body surface
      area, heart rate, frame rate, tissue-tracking methodology, equipment, or
      software. The metaregression showed that these effects were not significant
      determinants of variations among normal ranges of strain values. There was no
      evidence of publication bias (P = .59). CONCLUSIONS: This study is the first to
      define normal values of 2D STE-derived RV strain in children on the basis of a
      meta-analysis. The normal mean value in children for RV global strain is -29.03%
      (95% CI, -31.52% to -26.54%). The normal mean value for RV global systolic strain
      rate is -1.88 sec(-1) (95% CI, -2.10 to -1.59 sec(-1)). RV segmental strain has a
      stable base-to-apex gradient that highlights the dominance of deep longitudinal
      layers of the right ventricle that are aligned base to apex. Variations among
      different normal ranges did not appear to be dependent on differences in
      demographic, clinical, or equipment parameters in this meta-analysis. All of the
      eligible studies used equipment and software from one manufacturer (GE
      Healthcare).

PMID- 24582164
TI  - Elevated Plasma Oxidative Stress Markers in Individuals With Intermittent
      Explosive Disorder and Correlation With Aggression in Humans.
AB  - BACKGROUND: Animal and clinical studies suggest a link between inflammation and
      oxidative stress. Because oxidative stress is an inherent part of inflammation,
      and inflammation is associated with behavioral aggression in lower mammals and
      humans, we hypothesized that markers of oxidative stress would be related to
      aggression in human subjects. In this case-control study, markers of oxidative
      stress and aggression were assessed in human subjects with histories of
      recurrent, problematic, impulsive aggressive behavior and in nonaggressive
      comparator subjects. METHODS: Plasma levels of 8-hydroxy-2'-deoxyguanosine and 8
      isoprostane were examined in the context of measures of aggression and
      impulsivity in physically healthy subjects with intermittent explosive disorder
      (n = 69), nonaggressive subjects with Axis I or II disorders (n = 61), and
      nonaggressive subjects with no history of Axis I or II disorders (n = 67).
      RESULTS: Levels of plasma 8-hydroxy-2'-deoxyguanosine and 8-isoprostane were
      significantly higher in subjects with intermittent explosive disorder compared
      with psychiatric or normal control subjects. In addition, both oxidative stress
      markers correlated with a composite measure of aggression; more specifically, 8
      hydroxy-2'-deoxyguanosine correlated with measures reflecting a history of actual
      aggressive behavior in all subjects. CONCLUSIONS: These data suggest a positive
      relationship between plasma markers of oxidative stress and aggression in human
      subjects. This finding adds to the complex picture of the central neuromodulatory
      role of aggression in human subjects.

PMID- 24582165
TI  - Enterostomy closure timing for minimizing postoperative complications in
      premature infants.
AB  - BACKGROUND: For premature infants with advanced acute abdomen, creating a
      temporary enterostomy is believed to be an appropriate surgical management.
      However, there is no consensus regarding the timing of enterostomy reversal. The
      aim of this study was to determine the optimal timing for enterostomy closure
      (EC) by analyzing EC-related complications. METHODS: This was a retrospective
      study of preterm infants who underwent enterostomy for suspected acute abdomens
      and subsequent closure. RESULTS: EC-related complications occurred in 35 of 54
      infants (65%). A univariate analysis determined the following risk factors for EC
      related complications: lower weight and younger age at the time of EC and a
      shorter stoma duration. In a multiple logistic regression analysis, the only
      significant risk factor was a weight under 2660 g at the time of the closure
      operation. Infants with EC-related complications were ventilated longer, were
      administered more vasopressors, and were more likely to undergo reoperation.
      Additionally, these infants required parenteral nutrition for a longer duration,
      had a longer length of hospital stay after EC, and had a significantly lower
      weight and height at a corrected age of 7-10 months than infants without EC
      related complications. CONCLUSION: Body weight may be one of the most important
      factors to consider for minimizing EC-related complications.

PMID- 24582166
TI  - Effectiveness of vitamin A in the prevention of complications of prematurity.
AB  - BACKGROUND: To assess the effectiveness of vitamin A supplementation in very low
      birth weight (VLBW) infants to prevent complications of prematurity. METHODS:
      This was a retrospective cohort study to determine the effectiveness of vitamin A
      in preventing complications of prematurity in VLBW infants. Vitamin A was
      delivered intramuscularly at a dose of 5000 IU, three times weekly during the
      first 28 days of life. RESULTS: Of the 187 eligible VLBW infants, we excluded
      from the analysis (due to death or transfer to another hospital), 16 infants
      weighing <1000 g and 17 weighing 1000-1500 g. Sixty VLBW infants received the
      vitamin supplement. We observed no differences between the groups in the duration
      of oxygen therapy or in the risk of bronchopulmonary dysplasia. The risk of
      sepsis was up to three times higher among the infants who were given the vitamin
      A supplement. CONCLUSION: Given the increased risk of sepsis in patients weighing
      >1000 g, the risk associated with repeated intramuscular injections of vitamin A
      and the modest clinical results described, we do not believe the universal
      administration of vitamin A to VLBW infants to be justified as prophylaxis for
      bronchopulmonary dysplasia.

PMID- 24582167
TI  - Common variable immunodeficiency is associated with a functional deficiency of
      invariant natural killer T cells.
AB  - BACKGROUND: Common variable immunodeficiency (CVID) is the commonest symptomatic
      primary antibody disorder, with monogenic causes identified in less than 10% of
      all cases. X-linked proliferative disease is a monogenic disorder that is
      associated with hypogammaglobulinemia and characterized by a deficiency of
      invariant NKT (iNKT) cells. We sought to evaluate whether a defect in iNKT cell
      number or function was associated with CVID. OBJECTIVE: An evaluation of the
      function and number of iNKT cells in CVID. METHODS: Six-color flow cytometry
      enumerated iNKT cells in 36 patients with CVID and 50 healthy controls. Their
      proliferative capacity and cytokine production (IFN-gamma, IL-13, IL-17) was then
      investigated following activation with CD1d ligand alpha-galactosylceramide.
      RESULTS: A reduction in the number of iNKT cells (31 iNKT cells/10(5) T cells) in
      patients with CVID compared with healthy controls (100 iNKT cells/10(5) T cells)
      was observed (P < .0001). Two cohorts could be discerned within the CVID group:
      group 1 with an abnormal number of iNKT cells (n = 28) and group 2 with a normal
      number of iNKT cells (n = 8). This segregation coassociated with the
      proliferative capacity of iNKT cells between the 2 groups. However, differences
      in the function of iNKT cells were noted in group 2, in which an increase in IFN
      gamma (P = .0016) and a decrease in IL-17 (P = .0002) production was observed
      between patients with CVID and controls. Finally, a significant association was
      seen between the number of iNKT cells and the percentage of class-switched memory
      B cells and propensity to lymphoproliferation (P = .002) in patients with CVID.
      CONCLUSION: iNKT cells are deficient and/or functionally impaired in most of the
      patients with CVID.

PMID- 24582170
TI  - A description of U.S. post-graduation nurse residency programs.
AB  - BACKGROUND: Concern regarding newly licensed registered nurses' abilities to cope
      with the increasing complexity of care has led to the development of a variety of
      nurse residency program (NRP) initiatives. The unknowns are the extent to which
      and how various program elements are implemented across NRPs. Without
      understanding the extent to which NRPs deliver the same program, determination of
      their impact on care is limited. The purpose of this study was to describe U.S.
      NRPs and thereby identify the extent of treatment fidelity across programs.
      METHODS: Program attributes were measured using a 24-item survey based on the
      outcomes production conceptual framework. The survey was sent to known NRP
      directors or chief nursing officers at the 1,011 U.S. hospitals having 250 or
      more inpatient beds; 203 surveys (a 20% response rate) were returned. RESULTS:
      Almost half (48%) of hospitals reported operating an NRP. NRP models included
      University HealthSystems Consortium (22%), facility based (54%), and "other"
      (24%). Significant (p < .01) differences were noted among and within program
      model types in terms of career planning, project requirements and types, and
      mentoring. CONCLUSIONS: The extent of differences within and across program types
      indicates a lack of treatment fidelity needed to detect objectively the impact of
      the NRP as a discrete intervention on patient outcomes. NRP expansion may be
      limited by the number of hospitals of a size most likely able to support such
      programs.

PMID- 24582168
TI  - Integrating longitudinal information on pulmonary function and inflammation using
      asthma phenotypes.

PMID- 24582171
TI  - Innovations in prenatal genetic testing beyond the fetal karyotype.
AB  - Current trends in prenatal genetic testing will affect nursing practice,
      education, research, and policy making. Although fetal genetic testing has been
      the traditional focus, new technologies open the possibility of acquiring genomic
      information for both parents and offspring, revealing windows onto individuals'
      lifelong health. Noninvasive prenatal testing of cell-free fetal DNA also has
      become a reality. Some of the recent advances in detecting cytogenetic and
      heritable molecular variants in pregnancy are overviewed. Exemplars of prenatal
      tests are presented and related ethical, legal, and social implications are
      considered. Educating clinicians with updated genomic knowledge has been outpaced
      by new technologies and direct-to-consumer marketing of prenatal tests.
      Implications for nursing are discussed. 

PMID- 24582172
TI  - Endovascular abdominal aortic aneurysm repair using transvenous intravascular US
      catheter guidance in patients with chronic renal failure.
AB  - PURPOSE: To describe the transvenous application of intracardiac echocardiography
      (ICE) for guidance during endovascular aortic repair (EVAR). MATERIALS AND
      METHODS: Eight patients with an infrarenal abdominal aortic aneurysm (AAA) and
      chronic renal failure were determined suitable for EVAR. The procedure was
      performed by deploying the transcaval and transiliac vein guidance of an ICE
      catheter to reduce the dosage of iodinated contrast medium. Multiple guidance
      parameters were assessed. The present study describes the EVAR procedure and
      postprocedure transabdominal ultrasound (US) follow-up results at 3-4 months.
      RESULTS: The eight procedures were completed by using transvenous ICE guidance.
      No contrast medium was used in five patients, and 3-20 mL of isoosmolar contrast
      medium was administered in the other three. No endoleaks were detected by ICE
      immediately after stent deployment. One patient who had a single functioning
      kidney developed renal failure that was attributed to manipulation-related
      cholesterol embolization. That patient became dependent on dialysis and died 3.5
      months after the procedure. No endoleaks were detected at 3-4-month US follow-up
      in the other seven patients. CONCLUSIONS: Transvenous ICE guidance is a promising
      method to reduce the dosage of iodinated contrast medium in patients with renal
      dysfunction undergoing EVAR. A prospective trial comparing this modality versus
      digital subtraction angiography guidance with iodinated contrast medium in terms
      of safety, accuracy, and long-term efficacy is recommended.

PMID- 24582173
TI  - Brain magnetic resonance imaging findings in cryptogenic stroke patients under 60
      years with patent foramen ovale.
AB  - PURPOSE: To compare magnetic resonance imaging (MRI) brain feature in cryptogenic
      stroke patients with patent foramen ovale (PFO), cryptogenic stroke patients
      without PFO and patients with cardioembolic stroke. MATERIALS AND METHODS: The
      ethics committee required neither institutional review board approval nor
      informed patient consent for retrospective analyses of the patients' medical
      records and imaging data. The patients' medical files were retrospectively
      reviewed in accordance with human subject research protocols. Ninety-two patients
      under 60 years of age were included: 15 with cardioembolic stroke, 32 with
      cryptogenic stroke with PFO and 45 with cryptogenic stroke without PFO. Diffusion
      weighted imaging of brain MRI was performed by a radiologist blinded to clinical
      data. Univariate, Fischer's exact test for qualitative data and non-parametric
      Wilcoxon test for quantitative data were used. RESULTS: There was no
      statistically significant difference found between MRI features of patients with
      PFO and those with cardioembolic stroke (p<.05). Patients without PFO present
      more corticosubcortical single lesions (p<.05) than patients with PFO. Patients
      with PFO have more often subcortical single lesions larger than 15mm, involvement
      of posterior cerebral arterial territory and intracranial occlusion (p<.05) than
      patients with cryptogenic stroke without PFO. CONCLUSION: Our study suggests a
      cardioembolic mechanism in ischemic stroke with PFO.

PMID- 24582174
TI  - CT metal artefact reduction for internal fixation of the proximal humerus: value
      of mono-energetic extrapolation from dual-energy and iterative reconstructions.
AB  - AIM: To assess the value of dual-energy computed tomography (DECT) and an
      iterative frequency split-normalized metal artefact reduction (IFS-MAR) algorithm
      compared to filtered back projections (FBP) from single-energy CT (SECT) for
      artefact reduction in internally fixated humeral fractures. MATERIALS AND
      METHODS: Six internally fixated cadaveric humeri were examined using SECT and
      DECT. Data were reconstructed using FBP, IFS-MAR, and mono-energetic DECT
      extrapolations. Image analysis included radiodensity values and qualitative
      evaluation of artefacts, image quality, and level of confidence for localizing
      screw tips. RESULTS: Radiodensity values of streak artefacts were significantly
      different (p < 0.05) between FBP (-104 +/- 222) and IFS-MAR (73 +/- 122), and
      between FBP and DECT (32 +/- 151), without differences between IFS-MAR and DECT
      (p < 0.553). Compared to FBP, qualitative artefacts were significantly reduced
      using IFS-MAR (p < 0.001) and DECT (p < 0.05), without significant differences
      between IFS-MAR and DECT (p < 0.219). Image quality significantly (p = 0.016)
      improved for IFS-MAR and DECT compared to FBP, without significant differences
      between IFS-MAR and DECT (p < 0.553). The level of confidence for screw tip
      localization was assessed as best for DECT in all cases. CONCLUSION: Both IFS-MAR
      in SECT and mono-energetic DECT produce improved image quality and a reduction of
      metal artefacts. Screw tip positions can be most confidently assessed using DECT.

PMID- 24582175
TI  - Non-contrast-enhanced MR angiography of uterine arteries with balanced steady
      state free precession and time-space labelling inversion pulse: technical
      optimization and preliminary results.

PMID- 24582176
TI  - Current status of nephrogenic systemic fibrosis.
AB  - Nephrogenic systemic fibrosis (NSF) occurs in patients with advanced chronic
      kidney disease (CKD) or acute renal failure, most commonly following exposure to
      gadolinium-based contrast agents (GBCAs). NSF can be debilitating and associated
      with increased mortality. The putative association of NSF with GBCAs prompted the
      development of guidelines to limit the use of these contrast agents in at-risk
      patients. Indeed, the incidence of NSF has decreased dramatically following
      application of these guidelines, which appears to be the only effective means of
      decreasing NSF incidence. Thus, increasing clinician awareness of these updated
      guidelines is important. The present review introduces and compares updated
      guidelines for GBCA use and discusses the latest advances in the understanding of
      the pathogenic mechanisms and treatment of NSF. 

PMID- 24582177
TI  - CT and MRI of pulmonary valvular abnormalities.
AB  - Pulmonary valve disease constitutes a wide spectrum of conditions. Traditionally,
      echocardiography has been the technique of choice for the evaluation of pulmonary
      and other valvular disease. However, with advances in technology, computed
      tomography (CT) and magnetic resonance imaging (MRI) are playing increasingly
      important roles in the evaluation of these disorders. In this article, we review
      the normal appearance of the pulmonary valve and then illustrate various variants
      and pathological entities of the pulmonary valve. 

PMID- 24582178
TI  - Risk of endotoxemia associated with clinical incidence of contaminated propofol.

PMID- 24582179
TI  - Interaction between vitamin D receptor gene polymorphisms and 25-hydroxyvitamin D
      concentrations on metabolic and cardiovascular disease outcomes.
AB  - AIM: 25-hydroxyvitamin D (25OHD) concentrations have been shown to be associated
      with major clinical outcomes, with a suggestion that individual risk may vary
      according to common genetic differences in the vitamin D receptor (VDR) gene.
      Hence, we tested for the interactions between two previously studied VDR
      polymorphisms and 25OHD on metabolic and cardiovascular disease-related outcomes
      in a large population-based study. METHODS: Interactions between two previously
      studied VDR polymorphisms (rs7968585 and rs2239179) and 25OHD concentrations on
      metabolic and cardiovascular disease-related outcomes such as obesity- (body mass
      index, waist circumference, waist-hip ratio (WHR)), cardiovascular- (systolic and
      diastolic blood pressure), lipid- (high- and low-density lipoprotein,
      triglycerides, total cholesterol), inflammatory- (C-reactive protein, fibrinogen,
      insulin growth factor-1, tissue plasminogen activator) and diabetes- (glycated
      haemoglobin) related markers were examined in the 1958 British Birth cohort (n up
      to 5160). Interactions between each SNP and 25OHD concentrations were assessed
      using linear regression and the likelihood ratio test. RESULTS: After Bonferroni
      correction, none of the interactions reached statistical significance except for
      the interaction between the VDR SNP rs2239179 and 25OHD concentrations on waist
      hip ratio (WHR) (P=0.03). For every 1nmol/L higher 25OHD concentrations, the
      association with WHR was stronger among those with two major alleles (-4.0%,
      P=6.26e(-24)) compared to those with either one or no major alleles (-2.3%,
      P<=8.201e(-07), for both) of the VDR SNP rs2239179. CONCLUSION: We found no
      evidence for VDR polymorphisms acting as major modifiers of the association
      between 25OHD concentrations and cardio-metabolic risk. Interaction between VDR
      SNP rs2239179 and 25OHD on WHR warrants further confirmation.

PMID- 24582180
TI  - The incidence of coring with blunt versus sharp needles.
AB  - With the advent of safety needles to prevent inadvertent needle sticks in the
      operating room (OR), a potentially new issue has arisen. These needles may result
      in coring, or the shaving off of fragments of the rubber stopper, when the needle
      is pierced through the rubber stopper of the medication vial. These fragments may
      be left in the vial and then drawn up with the medication and possibly injected
      into patients. The current study prospectively evaluated the incidence of coring
      when blunt and sharp needles were used to pierce rubber topped vials. We also
      evaluated the incidence of coring in empty medication vials with rubber tops. The
      rubber caps were then pierced with either an18-gauge sharp hypodermic needle or a
      blunt plastic (safety) needle. Coring occurred in 102 of 250 (40.8%) vials when a
      blunt needle was used versus 9 of 215 (4.2%) vials with a sharp needle (P <
      0.0001). A significant incidence of coring was demonstrated when a blunt plastic
      safety needle was used. This situation is potentially a patient safety hazard and
      methods to eliminate this problem are needed. 

PMID- 24582181
TI  - Cesarean delivery in a pregnant woman with mutilating recessive dystrophic
      epidermolysis bullosa.

PMID- 24582182
TI  - Intubation difficulties in a patient with an esophageal foreign body.

PMID- 24582183
TI  - A ruptured pheochromocytoma: an unlikely cause of Brown-Sequard syndrome.

PMID- 24582184
TI  - The Affordable Care Act: early implications for fertility medicine.

PMID- 24582185
TI  - Stethoscopes and health care-associated infection.

PMID- 24582186
TI  - Looking for the treatment for drug shortages: not a simple prescription.

PMID- 24582187
TI  - You trained at Mayo Clinic? Wow!

PMID- 24582188
TI  - Contamination of stethoscopes and physicians' hands after a physical examination.
AB  - OBJECTIVES: To compare the contamination level of physicians' hands and
      stethoscopes and to explore the risk of cross-transmission of microorganisms
      through the use of stethoscopes. PATIENTS AND METHODS: We conducted a structured
      prospective study between January 1, 2009, and May 31, 2009, involving 83
      inpatients at a Swiss university teaching hospital. After a standardized physical
      examination, 4 regions of the physician's gloved or ungloved dominant hand and 2
      sections of the stethoscopes were pressed onto selective and nonselective media;
      489 surfaces were sampled. Total aerobic colony counts (ACCs) and total
      methicillin-resistant Staphylococcus aureus (MRSA) colony-forming unit (CFU)
      counts were assessed. RESULTS: Median total ACCs (interquartile range) for
      fingertips, thenar eminence, hypothenar eminence, hand dorsum, stethoscope
      diaphragm, and tube were 467, 37, 34, 8, 89, and 18, respectively. The
      contamination level of the diaphragm was lower than the contamination level of
      the fingertips (P<.001) but higher than the contamination level of the thenar
      eminence (P=.004). The MRSA contamination level of the diaphragm was higher than
      the MRSA contamination level of the thenar eminence (7 CFUs/25 cm(2) vs 4 CFUs/25
      cm(2); P=.004). The correlation analysis for both total ACCs and MRSA CFU counts
      revealed that the contamination level of the diaphragm was associated with the
      contamination level of the fingertips (Spearman's rank correlation coefficient,
      rho=0.80; P<.001 and rho=0.76; P<.001, respectively). Similarly, the
      contamination level of the stethoscope tube increased with the increase in the
      contamination level of the fingertips for both total ACCs and MRSA CFU counts
      (rho=0.56; P<.001 and rho=.59; P<.001, respectively). CONCLUSION: These results
      suggest that the contamination level of the stethoscope is substantial after a
      single physical examination and comparable to the contamination of parts of the
      physician's dominant hand.

PMID- 24582189
TI  - Racial disparities in survival for patients with clinically localized prostate
      cancer adjusted for treatment effects.
AB  - OBJECTIVE: To examine whether racial disparities in survival exist among black,
      Hispanic, and Asian patients compared with white patients with clinically
      localized prostate cancer (CLPC) after adjustment for the effects of treatment.
      PATIENTS AND METHODS: We performed a retrospective cohort study of patients with
      CLPC diagnosed from January 1, 1995, through December 31, 2003, as documented in
      the Surveillance, Epidemiology, and End Results registry. Treatment-stratified,
      risk-adjusted Cox proportional hazards models were constructed. RESULTS: During
      the study period, CLPC was diagnosed in 294,160 patients. Of these patients,
      123,850 (42.1%) underwent surgery and 101,627 (34.5%) underwent radiotherapy,
      whereas 68,683 (23.3%) received no treatment. Overall 5-year and 10-year survival
      rates for Asians (85.6% and 67.6%, respectively), Hispanics (85.9% and 69.0%,
      respectively), and whites (83.9% and 65.7%, respectively) were higher than for
      blacks (81.5% and 61.7%, respectively) (P<.001). Prostate cancer-specific
      survival also varied significantly by race (P<.001). A risk-adjusted model
      stratified by primary treatment modality revealed that blacks had worse overall
      survival than whites (hazard ratio, 1.37; 95% CI, 1.33-1.41; P<.001), whereas
      Asians had better survival compared with whites (hazard ratio, 0.79; 95% CI, 0.76
      0.83; P<.001). After the effects of treatment were accounted for, Hispanics had
      similar overall survival compared with whites (hazard ratio, 0.97; 95% CI, 0.94
      1.01; P=.10). CONCLUSION: Blacks with CLPC have poorer survival than whites,
      whereas Asians have better survival, even after risk adjustment and
      stratification by treatment. These data may be relevant to US regions with large
      underserved populations that have limited access to health care.

PMID- 24582191
TI  - Isometric exercise training for blood pressure management: a systematic review
      and meta-analysis.
AB  - OBJECTIVE: To conduct a systematic review and meta-analysis quantifying the
      effects of isometric resistance training on the change in systolic blood
      pressure(SBP), diastolic blood pressure (DBP), and mean arterial pressure in
      subclinical populations and to examine whether the magnitude of change in SBP and
      DBP was different with respect to blood pressure classification. PATIENTS AND
      METHODS: We conducted a systematic review and meta-analysis of randomized
      controlled trials lasting 4 or more weeks that investigated the effects of
      isometric exercise on blood pressure in healthy adults (aged >=18 years) and were
      published in a peer-reviewed journal. PubMed, CINAHL, and the Cochrane Central
      Register of Controlled Trials were searched for trials reported between January
      1, 1966, and July 31, 2013. We included 9 randomized trials, 6 of which studied
      normotensive participants and 3 that studied hypertensive patients, that included
      a total of 223 participants (127 who underwent exercise training and 96
      controls). RESULTS: The following reductions were observed after isometric
      exercise training: SBP-mean difference (MD), -6.77 mm Hg (95% CI, -7.93 to -5.62
      mm Hg; P<.001); DBP-MD, -3.96 mm Hg (95% CI, -4.80 to -3.12 mm Hg; P<.001); and
      mean arterial pressure-MD, -3.94 mm Hg (95% CI, -4.73 to -3.16 mm Hg; P<.001). A
      slight reduction in resting heart rate was also observed (MD, -0.79 beats/min;
      95% CI, -1.23 to -0.36 beats/min; P=.003). CONCLUSION: Isometric resistance
      training lowers SBP, DBP, and mean arterial pressure. The magnitude of effect is
      larger than that previously reported in dynamic aerobic or resistance training.
      Our data suggest that this form of training has the potential to produce
      significant and clinically meaningful blood pressure reductions and could serve
      as an adjunctive exercise modality.

PMID- 24582190
TI  - Frequency and implication of autoimmune serologies in idiopathic pulmonary
      fibrosis.
AB  - OBJECTIVE: To assess the frequency and clinical implications of positive
      autoimmune serologies in patients with biopsy-confirmed idiopathic pulmonary
      fibrosis (IPF). PATIENTS AND METHODS: We reviewed the records of patients at our
      institution with biopsy-confirmed usual interstitial pneumonia (UIP) from January
      1, 1995, through December 31, 2010, for frequency and distribution of autoimmune
      serologies. Patients with IPF with and without positive serologies were compared.
      RESULTS: Three hundred eighty-nine consecutive patients with biopsy-confirmed IPF
      underwent serologic testing, with positive serologic test results being found in
      112 (29%). Of 2051 individual screening serologic tests performed, results of 163
      tests were positive (8%), with antinuclear antibody being the most frequent
      (47%). There was no difference in age at biopsy (P=.21), gender (P=.21), or
      presenting radiologic features between those with or without positive serology.
      More frequent use of immunosuppressive treatment (P=.02) was noted in those with
      positive serology. No survival difference was observed (log-rank; P=.43). Median
      follow-up for the whole cohort was 43.5 months. CONCLUSION: Positive autoimmune
      serology may occur in as much as one-third of the patients with biopsy-confirmed
      IPF with no associated clinical implication or survival advantage. Systematic use
      of autoimmune laboratory panels in patients without clinical features of
      connective tissue disease should be reconsidered in patients with suspected UIP
      on chest computed tomography scan or confirmed UIP on biopsy.

PMID- 24582192
TI  - A pooled analysis of waist circumference and mortality in 650,000 adults.
AB  - OBJECTIVES: To assess the independent effect of waist circumference on mortality
      across the entire body mass index (BMI) range and to estimate the loss in life
      expectancy related to a higher waist circumference. PATIENTS AND METHODS: We
      pooled data from 11 prospective cohort studies with 650,386 white adults aged 20
      to 83 years and enrolled from January 1, 1986, through December 31, 2000. We used
      proportional hazards regression to estimate hazard ratios (HRs) and 95% CIs for
      the association of waist circumference with mortality. RESULTS: During a median
      follow-up of 9 years (maximum, 21 years), 78,268 participants died. After
      accounting for age, study, BMI, smoking status, alcohol consumption, and physical
      activity, a strong positive linear association of waist circumference with all
      cause mortality was observed for men (HR, 1.52 for waist circumferences of >=110
      vs <90 cm; 95% CI, 1.45-1.59; HR, 1.07 per 5-cm increment in waist circumference;
      95% CI, 1.06-1.08) and women (HR, 1.80 for waist circumferences of >=95 vs <70
      cm; 95% CI, 1.70-1.89; HR, 1.09 per 5-cm increment in waist circumference; 95%
      CI, 1.08-1.09). The estimated decrease in life expectancy for highest vs lowest
      waist circumference was approximately 3 years for men and approximately 5 years
      for women. The HR per 5-cm increment in waist circumference was similar for both
      sexes at all BMI levels from 20 to 50 kg/m(2), but it was higher at younger ages,
      higher for longer follow-up, and lower among male current smokers. The
      associations were stronger for heart and respiratory disease mortality than for
      cancer. CONCLUSIONS: In white adults, higher waist circumference was positively
      associated with higher mortality at all levels of BMI from 20 to 50 kg/m(2).
      Waist circumference should be assessed in combination with BMI, even for those in
      the normal BMI range, as part of risk assessment for obesity-related premature
      mortality.

PMID- 24582194
TI  - My treatment approach to management of the pregnant patient with inflammatory
      bowel disease.
AB  - Inflammatory bowel disease (IBD) is frequently diagnosed in women of childbearing
      age. Of paramount concern are questions about the effect of the disease on a
      woman's ability to conceive and carry the pregnancy safely to term, as well as
      the effect of the disease and its therapies on the health of the fetus. For
      health care providers, there is also the issue of medication dose adjustments and
      management of flares during pregnancy. Growing experience with IBD in pregnancy
      suggests that most women will have good outcomes; however, concerns and
      uncertainty remain for both the patient and the physician. This article outlines
      our approach to the treatment of these patients with respect to preconception
      counseling and management during pregnancy and the postpartum period. 

PMID- 24582193
TI  - Safety and efficacy of extracorporeal shock wave myocardial revascularization
      therapy for refractory angina pectoris.
AB  - OBJECTIVE: To assess the safety and efficacy of extracorporeal shockwave
      myocardial revascularization (ESMR) therapy in treating patients with refractory
      angina pectoris. PATIENTS AND METHODS: A single-arm multicenter prospective trial
      to assess safety and efficacy of the ESMR therapy in patients with refractory
      angina (class III/IV angina) was performed. Screening exercise treadmill tests
      and pharmacological single-photon emission computed tomography (SPECT) were
      performed for all patients to assess exercise capacity and ischemic burden.
      Patients were treated with 9 sessions of ESMR to ischemic areas over 9 weeks.
      Efficacy end points were exercise capacity by using treadmill test as well as
      ischemic burden on pharmacological SPECT at 4 months after the last ESMR
      treatment. Safety measures included electrocardiography, echocardiography,
      troponin, creatine kinase, and brain natriuretic peptide testing, and pain
      questionnaires. RESULTS: Fifteen patients with medically refractory angina and no
      revascularization options were enrolled. There was a statistically significant
      mean increase of 122.3+/-156.9 seconds (38% increase compared with baseline;
      P=.01) in exercise treadmill time from baseline (319.8+/-157.2 seconds) to last
      follow-up after the ESMR treatment (422.1+/-183.3 seconds). There was no
      improvement in the summed stress perfusion scores after pharmacologically induced
      stress SPECT at 4 months after the last ESMR treatment in comparison to that at
      screening; however, SPECT summed stress score revealed that untreated areas had
      greater progression in ischemic burden vs treated areas (3.69+/-6.2 vs 0.31+/
      4.5; P=.03). There was no significant change in the mean summed echo score from
      baseline to posttreatment (0.4+/-5.1; P=.70). The ESMR therapy was performed
      safely without any adverse events in electrocardiography, echocardiography,
      troponins, creatine kinase, or brain natriuretic peptide. Pain during the ESMR
      treatment was minimal (a score of 0.5+/-1.2 to 1.1+/-1.2 out of 10). CONCLUSION:
      In this multicenter feasibility study, ESMR seems to be a safe and efficacious
      treatment for patients with refractory angina pectoris. However, larger sham
      controlled trials will be required to confirm these findings.

PMID- 24582195
TI  - Drug shortages: a complex health care crisis.
AB  - National tracking of drug shortages began in 2001. However, a significant
      increase in the number of shortages began in late 2009, with numbers reaching
      what many have termed crisis level. The typical drug in short supply is a generic
      product administered by injection. Common classes of drugs affected by shortages
      include anesthesia medications, antibiotics, pain medications, nutrition and
      electrolyte products, and chemotherapy agents. The economic and clinical effects
      of drug shortages are significant. The financial effect of drug shortages is
      estimated to be hundreds of millions of dollars annually for health systems
      across the United States. Clinically, patients have been harmed by the lack of
      drugs or inferior alternatives, resulting in more than 15 documented deaths. Drug
      shortages occur for a variety of reasons. Generic injectable drugs are
      particularly susceptible to drug shortages because there are few manufacturers of
      these products and all manufacturers are running at full capacity. In addition,
      some manufacturers have had production problems, resulting in poor quality
      product. Although many suppliers are working to upgrade facilities and add
      additional manufacturing lines, these activities take time. A number of
      stakeholder organizations have been involved in meetings to further determine the
      causes and effects of drug shortages. A new law was enacted in July 2012 that
      granted the Food and Drug Administration additional tools to address the drug
      shortage crisis. The future of drug shortages is unknown, but there are hopeful
      indications that quality improvements and additional capacity may decrease the
      number of drug shortages in the years to come. 

PMID- 24582196
TI  - Alcohol and cardiovascular health: the dose makes the poison...or the remedy.
AB  - Habitual light to moderate alcohol intake (up to 1 drink per day for women and 1
      or 2 drinks per day for men) is associated with decreased risks for total
      mortality, coronary artery disease, diabetes mellitus, congestive heart failure,
      and stroke. However, higher levels of alcohol consumption are associated with
      increased cardiovascular risk. Indeed, behind only smoking and obesity, excessive
      alcohol consumption is the third leading cause of premature death in the United
      States. Heavy alcohol use (1) is one of the most common causes of reversible
      hypertension, (2) accounts for about one-third of all cases of nonischemic
      dilated cardiomyopathy, (3) is a frequent cause of atrial fibrillation, and (4)
      markedly increases risks of stroke-both ischemic and hemorrhagic. The risk-to
      benefit ratio of drinking appears higher in younger individuals, who also have
      higher rates of excessive or binge drinking and more frequently have adverse
      consequences of acute intoxication (for example, accidents, violence, and social
      strife). In fact, among males aged 15 to 59 years, alcohol abuse is the leading
      risk factor for premature death. Of the various drinking patterns, daily low- to
      moderate-dose alcohol intake, ideally red wine before or during the evening meal,
      is associated with the strongest reduction in adverse cardiovascular outcomes.
      Health care professionals should not recommend alcohol to nondrinkers because of
      the paucity of randomized outcome data and the potential for problem drinking
      even among individuals at apparently low risk. The findings in this review were
      based on a literature search of PubMed for the 15-year period 1997 through 2012
      using the search terms alcohol, ethanol, cardiovascular disease, coronary artery
      disease, heart failure, hypertension, stroke, and mortality. Studies were
      considered if they were deemed to be of high quality, objective, and
      methodologically sound. 

PMID- 24582197
TI  - Succinct review of the new VTE prevention and management guidelines.
AB  - Venous thromboembolism is a major source of morbidity and mortality in the United
      States. The American College of Chest Physicians Antithrombotic Guidelines, 9th
      edition, includes a large number of clinical practice recommendations regarding
      the diagnosis, treatment, and prevention of venous thromboembolism. This succinct
      clinical review of these guidelines specifically focuses on the evaluation,
      treatment, and prevention of venous thromboembolic disease. 

PMID- 24582198
TI  - 84-year-old man with night sweats, weight loss, and diarrhea.

PMID- 24582200
TI  - Anesthesia-assisted sedation getting notice by Medicare.

PMID- 24582201
TI  - Anesthesia-Assisted sedation getting notice by Medicare.

PMID- 24582202
TI  - Population-wide sodium reduction: reasons to resist.

PMID- 24582199
TI  - Cellular therapy for liver disease.
AB  - Regenerative medicine is energizing and empowering basic science and has the
      potential to dramatically transform health care in the future. Given the
      remarkable intrinsic regenerative properties of the liver, as well as widespread
      adoption of regenerative strategies for liver disease (eg, liver transplant,
      partial hepatectomy, living donor transplant), hepatology has always been at the
      forefront of clinical regenerative medicine. However, an expanding pool of
      patients awaiting liver transplant, a limited pool of donor organs, and finite
      applicability of the current surgical approaches have created a need for more
      refined and widely available regenerative medicine strategies. Although cell
      based therapies have been used extensively for hematologic malignant diseases and
      other conditions, the potential application of cellular therapy for acute and
      chronic liver diseases has only more recently been explored. New understanding of
      the mechanisms of liver regeneration and repair, including activation of local
      stem/progenitor cells and contributions from circulating bone marrow-derived stem
      cells, provide the theoretical underpinnings for the rational use of cell-based
      therapies in clinical trials. In this review, we dissect the scientific rationale
      for various modalities of cell therapy for liver diseases being explored in
      animal models and review those tested in human clinical trials. We also attempt
      to clarify some of the important ongoing questions that need to be addressed in
      order to bring these powerful therapies to clinical translation. Discussions will
      cover transplant of hepatocytes and liver stem/progenitor cells as well as
      infusion or stimulation of bone marrow-derived stem cells. We also highlight
      tremendous scientific advances on the horizon, including the potential use of
      induced pluripotent stem cells and their derivatives as individualized
      regenerative therapy for liver disease. 

PMID- 24582203
TI  - Population-wide sodium reduction: reasons to resist.

PMID- 24582204
TI  - Pediatrics practice at Mayo Clinic - a historical vignette.

PMID- 24582205
TI  - A 68-year-old violinist who developed diplopia.

PMID- 24582207
TI  - [S. Demers et al. in reply to the article by J. Boujenah et al].

PMID- 24582208
TI  - [Prenatal three-vessel and tracheal view: normal features].
AB  - Congenital heart disease (CG) are mostly from a low-risk population. Their
      screening should be based on reproducible and easy to use methods. Prenatal
      echocardiographic analysis is based primarily on the analysis of the four
      chambers and great vessels. The study of general admission pathways generalized
      since the 1980s is performed on an axial section while that of great vessels is
      performed in most countries more recently using several views and remains
      difficult. We review the features, under normal circumstances, of the three
      vessel and tracheal view that allows via an axial section of the fetal thorax to
      assess at the same time the trunk of the main pulmonary artery and its branches,
      the convergence of the ductus arteriosus and the aortic arches, the superior vena
      cava, and the trachea. Furthermore, the use of color Doppler mode optimizes the
      information obtained by this view. 

PMID- 24582209
TI  - John Thomas sign--a memorable but misleading sign in hip fractures.
AB  - OBJECTIVE: The John Thomas sign is a favourite of medical students and theorizes
      that in femoral neck fractures, the male member will lie to the side of the
      fracture on the plain radiograph. The aim of this study was to evaluate the
      accuracy, and examine the phenomenon of eponymous signs. We sought to answer the
      following questions: (1) How accurate is the sign in the context of a consecutive
      series of male patients with hip fractures? (2) Is there a relationship between
      side and size of penile lie and the side of fracture? HYPOTHESIS: That the
      accuracy of the John Thomas sign is, like many eponymous signs, spurious.
      MATERIALS AND METHODS: Two hundred male AP pelvis radiographs were examined, of
      which 100 had a hip fracture and compared these against 100 control films that
      did not. Age at presentation, and the side, length and angle of penile lie were
      measured. RESULTS: The results show two findings: that the accuracy of the
      supposed "sign" is less accurate than the toss of a coin; and that left lie and
      left-sided fractures are more common. We fail to show a relationship between side
      of fracture, John Thomas size or degree of angulation. CONCLUSION: John Thomas
      sign is no better than the toss of a coin in relation to hip fractures, and is
      not related to side of fracture, or penile attitude. We propose that the side of
      lie observed in male fractures may be as a result of handedness or natural
      underlying body asymmetry rather than as a result of the fracture. LEVEL OF
      EVIDENCE: Level III Case control study.

PMID- 24582210
TI  - Laterality, evolution and the IPL in the semantic-action system: Comment on
      "Action semantics: A unifying conceptual framework for the selective use of
      multimodal and modality-specific object knowledge" by Michiel van Elk, Hein van
      Schie, Harold Bekkering.

PMID- 24582211
TI  - Gemcitabine chemotherapy induces phenotypic alterations of tumor cells that
      facilitate antitumor T cell responses in a mouse model of oral cancer.
AB  - OBJECTIVES: Gemcitabine (GEM) is a pyrimidine nucleoside analogue that is a new
      chemotherapeutic agent used for treating various cancers. Because accumulating
      evidence indicates that GEM may activate host immune responses, its potential as
      an immune modulator in cancer chemotherapy has generated considerable interest.
      MATERIALS AND METHODS: In the present study, we investigated the antitumor
      effects of GEM using a mouse oral cancer model using immunological analyses. We
      examined apoptotic cell death of tumor cells with GEM treatment both in vitro and
      in vivo. We also investigated whether in vivo administration of GEM affected the
      distributions of immune cells, tumor-cell surface expression levels of immune
      accessory molecules and T cell immune responses in tumor-bearing mice. RESULTS:
      GEM induced significant oral cancer-cell apoptosis in vitro, and in vivo GEM
      administration markedly attenuated established mouse tumor growth. In vivo GEM
      administration decreased the numbers of both myeloid-derived suppressor cells
      (MDSCs) and B cells in tumor-bearing mice and enhanced dendritic cell maturation.
      Moreover, GEM treatment upregulated tumor-cell surface expressions of several
      immune accessory molecules and adhesion molecules, including CD80, CD86, CD40,
      ICAM-1, VCAM-1, and P-selectin. Remarkably, these tumor cells augmented tumor
      specific T-cell responses. CONCLUSION: These results suggest that GEM can induce
      host antitumor immune responses, which would facilitate antitumor effects in the
      treatment of oral cancer.

PMID- 24582212
TI  - Cancer-specific administrative data-based comorbidity indices provided valid
      alternative to Charlson and National Cancer Institute Indices.
AB  - OBJECTIVE: We aimed to develop and validate administrative data-based comorbidity
      indices for a range of cancer types that included all relevant concomitant
      conditions. STUDY DESIGN AND SETTINGS: Patients diagnosed with colorectal,
      breast, gynecological, upper gastrointestinal, or urological cancers identified
      from the National Cancer Registry between July 1, 2006 and June 30, 2008 for the
      development cohort (n=14,096) and July 1, 2008 to December 31, 2009 for the
      validation cohort (n=11,014) were identified. A total of 50 conditions were
      identified using hospital discharge data before cancer diagnosis. Five site
      specific indices and a combined site index were developed, with conditions
      weighted according to their log hazard ratios from age- and stage-adjusted Cox
      regression models with noncancer death as the outcome. We compared the
      performance of these indices (the C3 indices) with the Charlson and National
      Cancer Institute (NCI) comorbidity indices. RESULTS: The correlation between the
      Charlson and C3 index scores ranged between 0.61 and 0.78. The C3 index
      outperformed the Charlson and NCI indices for all sites combined, colorectal, and
      upper gastrointestinal cancer, performing similarly for urological, breast, and
      gynecological cancers. CONCLUSION: The C3 indices provide a valid alternative to
      measuring comorbidity in cancer populations, in some cases providing a modest
      improvement over other indices.

PMID- 24582213
TI  - Edema and fibrosis imaging by cardiovascular magnetic resonance: how can the
      experience of Cardiology be best utilized in rheumatological practice?
AB  - OBJECTIVES: CMR, a non-invasive, non-radiating technique can detect myocardial
      oedema and fibrosis. METHOD: CMR imaging, using T2-weighted and T1-weighted
      gadolinium enhanced images, has been successfully used in Cardiology to detect
      myocarditis, myocardial infarction and various cardiomyopathies. RESULTS:
      Transmitting this experience from Cardiology into Rheumatology may be of
      important value because: (a) heart involvement with atypical clinical
      presentation is common in autoimmune connective tissue diseases (CTDs). (b) CMR
      can reliably and reproducibly detect early myocardial tissue changes. (c) CMR can
      identify disease acuity and detect various patterns of heart involvement in CTDs,
      including myocarditis, myocardial infarction and diffuse vasculitis. (d) CMR can
      assess heart lesion severity and aid therapeutic decisions in CTDs. CONCLUSION:
      The CMR experience, transferred from Cardiology into Rheumatology, may facilitate
      early and accurate diagnosis of heart involvement in these diseases and
      potentially targeted heart treatment.

PMID- 24582214
TI  - Membrane potential-dependent uptake of 18F-triphenylphosphonium--a new voltage
      sensor as an imaging agent for detecting burn-induced apoptosis.
AB  - BACKGROUND: Mitochondrial dysfunction has been closely related to many pathologic
      processes, such as cellular apoptosis. Alterations in organelle membrane
      potential are associated with mitochondrial dysfunction. A fluorine-18 labeled
      phosphonium compound: (18)F-triphenylphosphonium ((18)F-TPP) was prepared to
      determine its potential use as a mitochondria-targeting radiopharmaceutical to
      evaluate cellular apoptosis. METHODS: Studies were conducted in both ex vivo cell
      lines and in vivo using a burned animal model. Uptake of (18)F-TPP was assessed
      in PC-3 cells by gamma counting under the following conditions: graded levels of
      extracellular potassium concentrations, incubation with carbonyl cyanide m
      chlorophenylhydrazone and staurosporine. Apoptosis was studied in a burn animal
      model using terminal deoxynucleotidyl transferase dUTP nick end labeling staining
      and simultaneous assessment of (18)F-TPP uptake by biodistribution. RESULTS: We
      found that stepwise membrane depolarization by potassium (K) resulted in a linear
      decrease in (18)F-TPP uptake, with a slope of 0.62 +/- 0.08 and a correlation
      coefficient of 0.936 +/- 0.11. Gradually increased concentrations of m
      chlorophenylhydrazone lead to decreased uptake of (18)F-TPP. Staurosporine
      significantly decreased the uptake of (18)F-TPP in PC-3 cells from 14.2 +/- 3.8%
      to 5.6 +/- 1.3% (P < 0.001). Burn-induced significant apoptosis (sham: 4.4 +/-
      1.8% versus burn: 24.6 +/- 6.7 %; P < 0.005) and a reduced uptake of tracer in
      the spleens of burn-injured animals as compared with sham burn controls (burn:
      1.13 +/- 0.24% versus sham: 3.28 +/- 0.67%; P < 0.005). Biodistribution studies
      demonstrated that burn-induced significant reduction in (18)F-TPP uptake in
      spleen, heart, lung, and liver, which were associated with significantly
      increased apoptosis. CONCLUSIONS: (18)F-TPP is a promising new voltage sensor for
      detecting mitochondrial dysfunction and apoptosis in various tissues.

PMID- 24582215
TI  - Microstructure and self-sharpening of the magnetite cap in chiton tooth.
AB  - The magnetite cap of chiton tooth (Acanthochiton rubrolineatus) was studied with
      SEM. Three microstructurally distinct regions were recognized: Region I, close to
      the anterior surface of the cusp and composed of thick rod microstructure units;
      Region III, close to the posterior surface and composed of fine fibers; and
      Region II, sandwiched between Regions I and II and composed of thin sheets. The
      microstructure units in the three regions constitute a continuous and integrated
      architecture component. The hardness of Regions I and II was measured to be Hv270
      and Hv490, respectively. Based on these microstructure observation and hardness
      data, the abrasive behavior and microstructural mechanism of self-sharpening of
      the chiton tooth were discussed in the paper. The self-sharpening was attributed
      to the combined effect of the hardness and the texture orientation of the
      microstructure units in Regions I and II. 

PMID- 24582216
TI  - Reversible stress softening of collagen based networks from the jumbo squid
      mantle (Dosidicus gigas).
AB  - Dosidicus gigas is the largest and one of the most abundant jumbo squids in the
      eastern Pacific Ocean. In this paper we have studied the muscle of the mantle of
      D. gigas (DGM). Morphological, thermal and rheological properties were assessed
      by means of atomic force microscopy, scanning electron microscopy, energy
      dispersive X-ray spectroscopy, differential scanning calorimetry,
      thermogravimetry and oscillatory rheometry. This study allowed us to assess the
      morphological and rheological properties of a collagen based network occurring in
      nature. The results showed that the DGM network displays a nonlinear effect
      called reversible stress softening (RSS) that has been previously described for
      other types of biological structures such as naturally occurring cellulose
      networks and actin networks. We propose that the RSS could play a key role on the
      way jumbo squids withstand hydrostatic pressure. The results presented here
      confirm that this phenomenon occurs in a wider number of materials than
      previously thought, all of them exhibiting different size scales as well as
      physical conformation. 

PMID- 24582217
TI  - Electrochemical determination of estradiol using a thin film containing reduced
      graphene oxide and dihexadecylphosphate.
AB  - Graphene is a material that has attracted attention with regard to sensing and
      biosensing applications in recent years. Here, we report a novel treatment (using
      ultrasonic bath and ultrasonic tip) to obtain graphene oxide (GO) and a new
      stable conducting film using reduced graphene oxide (RGO) and
      dihexadecylphosphate film (DHP). The GO was obtained by chemical exfoliation and
      it was reduced using NaBH4. Subsequently, RGO-DHP dispersion was prepared and it
      was dropped onto a glassy carbon electrode by casting technique. The electrode
      was characterized by cyclic voltammetry and electrochemical spectroscopy
      impedance. The voltammetric behavior of the RGO-DHP/GC electrode in the presence
      of estradiol was studied, and the results reported an irreversible oxidation peak
      current at 0.6V. Under the optimal experimental conditions, using linear sweep
      adsorptive stripping voltammetry, the detection limit obtained for this hormone
      was 7.7*10(-8)mol L(-1). The proposed electrode can be attractive for
      applications as electrochemical sensors and biosensors.

PMID- 24582218
TI  - Starch and chitosan oligosaccharides as interpenetrating phases in poly(N
      isopropylacrylamide) injectable gels.
AB  - Thermosensitive interpenetrating gels were prepared by physically blending poly(N
      isopropylacrylamide) (PNIPA) as the matrix and the following polysaccharides as
      interpenetrating phases: chitosan oligosaccharides (identified as QNAD and QNED)
      and soluble starch (STARCH). The molecular weight of the dispersed phase, the
      free water/bound water ratio and the thermosensitivity (transition temperature:
      LCST) of the gels were determined. It was found that these gels are pseudoplastic
      and that their viscosity depends on the molecular weight of the dispersed phase.
      LCST transition occurred around 35-37 degrees C. The morphology of the porosity
      of the freeze-dried samples was studied by Scanning Electron Microscopy (SEM). An
      in vitro test of cell hemolysis on blood agar showed that these gels are
      noncytotoxic. According to the results obtained, these interpenetrating gels show
      characteristics of an injectable material, and have a transition LCST at body
      temperature, which reinforces their potential to be used in the surgical field
      and as scaffolds for tissue engineering. 

PMID- 24582219
TI  - Electrical stimulation to promote osteogenesis using conductive polypyrrole
      films.
AB  - In this study, we developed an electrical cell culture and monitoring device.
      Polypyrrole (PPy) films with different resistances were fabricated as conductive
      surfaces to investigate the effect of substrate-mediated electrical stimulation.
      The physical and chemical properties of the devices, as well as their
      biocompatibilities, were thoroughly evaluated. These PPy films had a dark but
      transparent appearance, on which the surface cells could be easily observed.
      After treating with the osteogenic medium, rat bone marrow stromal cells cultured
      on the PPy films differentiated into osteoblasts. The cells grown on the PPy
      films had up-regulated osteogenic markers, and an alkaline phosphatase activity
      assay showed that the PPy films accelerated cell differentiation. Alizarin red
      staining and calcium analysis suggested that the PPy films promoted osteogenesis.
      Finally, PPy films were subjected to a constant electric field to elucidate the
      effect of electrical stimulation on osteogenesis. Compared with the untreated
      group, electrical stimulation improved calcium deposition in the extracellular
      matrix. Furthermore, PPy films with lower resistances allowed larger currents to
      stimulate the surface cells, which resulted in higher levels of mineralization.
      Overall, these results indicated that this system exhibited superior
      electroactivity with controllable electrical resistance and that it can be coated
      directly to produce medical devices with a transparent appearance, which should
      be beneficial for research on electrical stimulation for tissue regeneration. 

PMID- 24582220
TI  - Silicon effect on the composition and structure of nanocalcium phosphates: In
      vitro biocompatibility to human osteoblasts.
AB  - Nanostructured calcium phosphates, such as nanohydroxyapatite (HAP) and HAP with
      silicon content (HAP-Si) of 0.47wt.% (1% SiO2), 2.34wt.% (5% SiO2) and 4.67wt.%
      (10% SiO2) in the final product, were synthesized by aqueous precipitation,
      freeze dried and then calcined at 650, 950 and 1150 degrees C. The obtained
      materials were investigated by X-ray diffraction (XRD), Fourier transform
      infrared (FTIR) spectrometry, transmission electron microscopy (TEM), scanning
      electron microscopy (SEM) and atomic force microscopy (AFM) imaging. From the
      analysis of the XRD patterns, the HAP and beta-tricalcium phosphate (beta-TCP)
      phases were identified and their amounts in the samples were estimated. The size
      of HAP and beta-TCP crystallites was estimated to be in the nanocrystalline
      domain. FTIR spectra showed the presence of characteristic vibrations for P-O, H
      O and Si-O groups and their modification with Si content and calcination
      temperature. TEM, SEM and AFM images also revealed the morphology of the
      particles and of their aggregates. These materials have been used to manufacture
      scaffolds which were tested for their influence on adhesion and proliferation of
      cells, in human osteoblast culture, considering their further use in bone
      reconstruction. It was found that an appropriate addition of silicon in
      nanocalcium phosphate scaffolds leads to an enhanced adhesion and proliferation
      of cells in osteoblasts in vitro. 

PMID- 24582221
TI  - Novel silk fibroin films prepared by formic acid/hydroxyapatite dissolution
      method.
AB  - Bombyx mori silk fibroin from the silkworm was firstly found to be soluble in
      formic acid/hydroxyapatite system. The rheological behavior of silk fibroin
      solution was significantly influenced by HAp contents in dissolved solution. At
      the same time, silk fibroin nanofibers were observed in dissolved solution with
      103.6+/-20.4nm in diameter. Moreover, the structure behavior of SF films prepared
      by formic acid/hydroxyapatite dissolution method was examined. The secondary
      structure of silk fibroin films was attributed to silk II structure (beta-sheet),
      indicating that the hydroxyapatite contents in dissolved solution were not
      significantly affected by the structure of silk fibroin. The X-ray diffraction
      results exhibited obviously hydroxyapatite crystalline nature existing in silk
      fibroin films; however, when the hydroxyapatite content was 5.0wt.% in dissolved
      solution, some hydroxyapatite crystals were converted to calcium hydrogen
      phosphate dehydrate in silk fibroin dissolution process. This result was also
      confirmed by Fourier transform infrared analysis and DSC measurement. In
      addition, silk fibroin films prepared by this dissolution method had higher
      breaking strength and extension at break. Based on these analyses, an
      understanding of novel SF dissolution method may provide an additional tool for
      designing and synthesizing advanced materials with more complex structures, which
      should be helpful in different fields, including biomaterial applications. 

PMID- 24582222
TI  - Preparation and characterization of antimicrobial nano-hydroxyapatite composites.
AB  - Deep infection of prosthesis is one of the most frequent complications after
      joint replacement. One of the most effective ways is to introduce directly some
      antibiotics in the local site of the surgery. In the present study, an
      antimicrobial composite has been fabricated using nano-hydroxyapatite particles
      as carriers for the antimicrobial drug of vancomycin hydrochloride (VAN) and the
      mixture of oxidation sodium alginate (OSA) and gelatin (GT) as a sticky matrix.
      Samples have been characterized using X-ray diffraction instrument (XRD), field
      emission scanning electron microscope (FE-SEM), transmission electron microscope
      (TEM) and Fourier transform infrared (FTIR) spectra, Brunauer-Emmett-Teller (BET)
      methods, the rotational rheometer and the texture analyzer. The release of VAN
      from nano-hydroxyapatite (nHAP) particles was detected by the ultraviolet-visible
      (UV-vis) spectrophotometer and then bactericidal property of the composite was
      evaluated using the Staphylococcus aureus (S. aureus) as a bacterial model.
      Experimental results showed that the composite possessed an adhesive property
      derived from the gel of OSA and GT, which implied that the composite could bond
      directly to the fracture surface of bones in surgery. Furthermore, VAN was loaded
      efficiently on the surface of nHAP particles and could be released slowly from
      these particles, which endowed the composite with an obvious and continuous
      antimicrobial performance. The sticky and antimicrobial composite may has a
      potential application in arthroplasty to overcome deep infection in a simple and
      direct manner. 

PMID- 24582223
TI  - Structure, properties and animal study of a calcium phosphate/calcium sulfate
      composite cement.
AB  - In-vitro and in-vivo studies have been conducted on an in-house-developed
      tetracalcium phosphate (TTCP)/dicalcium phosphate anhydrous (DCPA)/calcium
      sulfate hemihydrate (CSH)-derived composite cement. Unlike most commercial
      calcium-based cement pastes, the investigated cement paste can be directly
      injected into water and harden without dispersion. The viability value of cells
      incubated with a conditioned medium of cement extraction is >90% that of Al2O3
      control and >80% that of blank medium. Histological examination reveals excellent
      bonding between host bone and cement without interposition of fibrous tissues. At
      12 weeks-post implantation, significant remodeling activities are found and a new
      bone network is developed within the femoral defect. The 26-week samples show
      that the newly formed bone becomes more mature, while the interface between
      residual cement and the new bone appears less identifiable. Image analysis
      indicates that the resorption rate of the present cement is much higher than that
      of TTCP or TTCP/DCPA-derived cement under similar implantation conditions.

PMID- 24582224
TI  - A simple method to prepare modified polyethersulfone membrane with improved
      hydrophilic surface by one-pot: The effect of hydrophobic segment length and
      molecular weight of copolymers.
AB  - A simple method to prepare modified polyethersulfone (PES) membrane by one-pot is
      provided, and the method includes three steps: polymerization of vinyl
      pyrrolidone (VP), copolymerization of methyl methacrylate (MMA) and blending with
      PES. The effect of the PMMA segment length and molecular weight of the copolymer
      (PVP-b-PMMA-b-PVP, as an additive) on the structures and properties of the
      modified membranes was investigated. Activated partial thromboplastin time (APTT)
      tests indicated that with the increase of the poly(methyl methacrylate) (PMMA)
      segment length in the chains of the copolymers and with the increase of the
      molecular weight of the copolymers, the APTTs of the modified membranes increased
      to some extent, since less of the additives were lost during liquid-liquid phase
      separation process. Therefore, the copolymer was designed and prepared with
      appropriate ratio of poly(vinyl pyrrolidone) (PVP) to MMA and with appropriate
      molecular weight for better membrane performance. When the copolymer was blended
      in the membrane, the water permeance, protein anti-fouling property and sieving
      coefficients for PEG-12000 increased obviously. The simple, credible and feasible
      method had the potential to be used for the modification of membranes with
      improved blood compatibility, ultrafiltration and antifouling properties of
      biomaterials and for practical production. 

PMID- 24582225
TI  - Mechanical and chemical analyses across dental porcelain fused to CP titanium or
      Ti6Al4V.
AB  - The aim of this study was to evaluate the evolution of mechanical properties and
      chemical variation across veneering dental porcelain fused to different titanium
      based substrates. Test samples were synthesized by fusing dental feldspar-based
      porcelain onto commercially pure titanium grade II or Ti6Al4V alloy. Samples were
      cross-sectioned at angles of 10 and 90 degrees  to the interface plane.
      Afterwards, nanoindentation tests and Scanning Electron Microscopy (SEM) imaging
      coupled to an Energy Dispersive Spectroscopy (EDS) system were carried out across
      interfaces extending from the metal towards the porcelain area. Elemental
      diffusion profiles across the porcelain-to-metal interfaces were also obtained by
      EDS analysis. The mismatch in mechanical properties found in porcelain-to-Ti6Al4V
      interfaces was lower than that of porcelain-to-CP titanium. Cracking was noticed
      at low-thickness veneering dental porcelain regions after the nanoindentation
      tests of samples cross-sectioned at low angles to the interface plane. A wide
      reaction zone between titanium and porcelain as well as higher incidence of
      defects was noticed at the porcelain-to-CP titanium interfaces. This study
      confirmed Ti6Al4V as an improved alternative to CP-titanium as it showed to
      establish a better interface with the veneering dental porcelain considering the
      slight chemical interaction and the lower mechanical properties mismatch. The
      elastic modulus of porcelain-to-Ti6Al4V samples showed to be less sensitive to
      porcelain thickness variations. 

PMID- 24582226
TI  - Finite element analysis of depth effect on measuring elastic modulus of a core
      shell structure for application of instrumented indentation in tooth enamel.
AB  - Tooth enamel is a complex structure, consisting of numerous enamel rods
      surrounded by a protein-rich sheath. Considering the possible effect of the
      protein-rich sheath on the indentation deformation of an enamel rod and the
      limitation of the Oliver-Pharr method in measuring the elastic modulus of the
      enamel rod, we used a finite element method to analyze the indentation
      deformation of an elastic-perfectly plastic cylinder surrounded by an elastic
      perfectly plastic film. A concept of the threshold indentation depth was
      proposed, at which the percentage error of the measured modulus of the cylinder
      is +/-10%. For the indentation depth less than the threshold indentation depth,
      the elastic modulus measured from the indentation test can be approximated as the
      intrinsic elastic modulus of the cylinder. The normalized threshold indentation
      depth strongly depends on the modulus ratio of the film to the cylinder and the
      ratio of the film thickness to the cylinder radius. The results can be used to
      guide the use of the Oliver-Pharr method in characterizing the mechanical
      properties of tooth enamel and bio-composites with core-shell structures. 

PMID- 24582227
TI  - A novel coated platinum electrode for oseltamivir determination in
      pharmaceuticals.
AB  - New coated platinum selective electrodes have been prepared and used for the
      determination of oseltamivir phosphate (OSL) in bulk drug solutions and in
      pharmaceutical preparations. Electrodes were using plasticized PVC membranes
      doped with ion-pair complexes based on drug-phosphomolybdate and drug
      tetraphenylborate as electroactive materials. The influence of membrane
      composition (plasticizers and ion-pair complexes) has been investigated. Optimum
      performance was obtained for two polymeric membranes: PVC:o-NPPE:OSL-TPB in the
      ratio of 30:68:2 (%, w:w:w) and PVC:DPP:OSL-PMA in the ratio of 30:68:2 (%,
      w:w:w). The electrodes exhibited linear responses over large concentration ranges
      (1.0*10(-5)-1.0*10(-2) and 5.0*10(-5)-5.0*10(-2)M, respectively) with near
      Nernstian responses (58.9 and 57.3mV/decade, respectively). The selectivity
      coefficients indicated good selectivity for OSL drug over a large number of
      organic compounds and some inorganic cations. The proposed electrodes were
      successfully applied to the determination of OSL in raw material and in
      pharmaceutical formulations. The results were validated by comparison with a
      capillary electrophoresis method. 

PMID- 24582228
TI  - Strategies to prepare TiO2 thin films, doped with transition metal ions, that
      exhibit specific physicochemical properties to support osteoblast cell adhesion
      and proliferation.
AB  - Metal ion doped titanium oxide (TiO2) thin films, as bioactive coatings on metal
      or other implantable materials, can be used as surfaces for studying the cell
      biological properties of osteogenic and other cell types. Bulk crystallite phase
      distribution and surface carbon-oxygen constitution of thin films, play an
      important role in determining the biological responses of cells that come in
      their contact. Here we present a strategy to control the polarity of atomic
      interactions between the dopant metal and TiO2 molecules and obtain surfaces with
      smaller crystallite phases and optimal surface carbon-oxygen composition to
      support the maximum proliferation and adhesion of osteoblast cells. Our results
      suggest that surfaces, in which atomic interactions between the dopant metals and
      TiO2 were less polar, could support better adhesion, spreading and proliferation
      of cells. 

PMID- 24582229
TI  - Electrocatalytic dechlorination of chloroacetic acids on silver nanodendrites
      electrode.
AB  - Silver nanodendrites were successfully prepared by electrodeposition on the
      glassy carbon electrode. The effects of synthesis parameters such as
      concentrations of reagents and applied potentials on the morphology and structure
      of silver nanodendrites have been investigated. Electrochemical experiments
      showed that silver nanodendrites electrode had extraordinary electrocatalytic
      activity toward the dechlorination of chloroacetic acids. The electrocatalytic
      hydrogenolysis mechanism was the main pathway for the dechlorination of
      chloroacetic acids. 

PMID- 24582230
TI  - Modified Au nanoparticles-imprinted sol-gel, multiwall carbon nanotubes pencil
      graphite electrode used as a sensor for ranitidine determination.
AB  - A new, simple, and disposable molecularly imprinted electrochemical sensor for
      the determination of ranitidine was developed on pencil graphite electrode (PGE)
      via cyclic voltammetry (CV). The PGEs were coated with MWCNTs containing the
      carboxylic functional group (f-MWCNTs), imprinted with sol-gel and Au
      nanoparticle (AuNPs) layers (AuNP/MIP-sol-gel/f-MWCNT/PGE), respectively, to
      enhance the electrode's electrical transmission and sensitivity. The thin film of
      molecularly imprinted sol-gel polymers with specific binding sites for ranitidine
      was cast on modified PGE by electrochemical deposition. The AuNP/MIP-sol-gel/f
      MWCNT/PGE thus developed was characterized by electrochemical impedance
      spectroscopy (EIS) and CV. The interaction between the imprinted sensor and the
      target molecule was also observed on the electrode by measuring the current
      response of 5.0mMK3[Fe(CN)6] solution as an electrochemical probe. The pick
      currents of ranitidine increased linearly with concentration in the ranges of
      0.05 to 2.0MUM, with a detection limit of (S/N=3) 0.02MUM. Finally, the modified
      electrode was successfully employed to determine ranitidine in human urine
      samples. 

PMID- 24582231
TI  - Surface functionalization of nanoporous alumina with bone morphogenetic protein 2
      for inducing osteogenic differentiation of mesenchymal stem cells.
AB  - Many studies have demonstrated the possibility to regulate cellular behavior by
      manipulating the specific characteristics of biomaterials including the physical
      features and chemical properties. To investigate the synergistic effect of
      chemical factors and surface topography on the growth behavior of mesenchymal
      stem cells (MSCs), bone morphorgenic protein 2 (BMP2) was immobilized onto porous
      alumina substrates with different pore sizes. The BMP2-immobilized alumina
      substrates were characterized with scanning electron microscopy (SEM) and X-ray
      photoelectron spectroscopy (XPS). Growth behavior and osteogenic differentiation
      of MSCs cultured on the different substrates were investigated. Cell adhesion and
      morphological changes were observed with SEM, and the results showed that the
      BMP2-immobilized alumina substrate was able to promote adhesion and spreading of
      MSCs. MTT assay and immunofluorescence staining of integrin beta1 revealed that
      the BMP2-immobilized alumina substrates were favorable for cell growth. To
      evaluate the differentiation of MSCs, osteoblastic differentiation markers, such
      as alkaline phosphatase (ALP) activity and mineralization, were investigated.
      Compared with those of untreated alumina substrates, significantly higher ALP
      activities and mineralization were detected in cells cultured on BMP2-immobilized
      alumina substrates. The results suggested that surface functionalization of
      nanoporous alumina substrates with BMP2 was beneficial for cell growth and
      osteogenic differentiation. With the approach of immobilizing growth factors onto
      material substrates, it provided a new insight to exploit novel biofunctional
      materials for tissue engineering. 

PMID- 24582232
TI  - Collagen tissue treated with chitosan solutions in carbonic acid for improved
      biological prosthetic heart valves.
AB  - Calcification of bovine pericardium dramatically shortens typical lifetimes of
      biological prosthetic heart valves and thus precludes their choice for younger
      patients. The aim of the present work is to demonstrate that the calcification is
      to be mitigated by means of treatment of bovine pericardium in solutions of
      chitosan in carbonic acid, i.e. water saturated with carbon dioxide at high
      pressure. This acidic aqueous fluid unusually combines antimicrobial properties
      with absolute biocompatibility as far as at normal pressure it decomposes
      spontaneously and completely into H2O and CO2. Yet, at high pressures it can
      protonate and dissolve chitosan materials with different degrees of acetylation
      (in the range of 16-33%, at least) without any further pretreatment. Even
      exposure of the bovine pericardium in pure carbonic acid solution without
      chitosan already favours certain reduction in calcification, somewhat improved
      mechanical properties, complete biocompatibility and evident antimicrobial
      activity of the treated collagen tissue. The reason may be due to high extraction
      ability of this peculiar compressed fluidic mixture. Moreover, exposure of the
      bovine pericardium in solutions of chitosan in carbonic acid introduces even
      better mechanical properties and highly pronounced antimicrobial activity of the
      modified collagen tissue against adherence and biofilm formation of relevant Gram
      positive and Gram-negative strains. Yet, the most important achievement is the
      detected dramatic reduction in calcification for such modified collagen tissues
      in spite of the fact that the amount of the thus introduced chitosan is rather
      small (typically ca. 1wt.%), which has been reliably detected using original
      tritium labelling method. We believe that these improved properties are achieved
      due to particularly deep and uniform impregnation of the collagen matrix with
      chitosan from its pressurised solutions in carbonic acid. 

PMID- 24582233
TI  - Understanding anisotropy and architecture in ice-templated biopolymer scaffolds.
AB  - Biopolymer scaffolds have great therapeutic potential within tissue engineering
      due to their large interconnected porosity and biocompatibility. Using an ice
      templated technique, where collagen is concentrated into a porous network by ice
      nucleation and growth, scaffolds with anisotropic pore architecture can be
      created, mimicking natural tissues like cardiac muscle and bone. This paper
      describes a systematic set of experiments undertaken to understand the effect of
      local temperatures on architecture in ice-templated biopolymer scaffolds. The
      scaffolds within this study were at least 10mm in all dimensions, making them
      applicable to critical sized defects for biomedical applications. It was found
      that monitoring the local freezing behavior within the slurry was critical to
      predicting scaffold structure. Aligned porosity was produced only in parts of the
      slurry volume which were above the equilibrium freezing temperature (0 degrees C)
      at the time when nucleation first occurs in the sample as a whole. Thus, to
      create anisotropic scaffolds, local slurry cooling rates must be sufficiently
      different to ensure that the equilibrium freezing temperature is not reached
      throughout the slurry at nucleation. This principal was valid over a range of
      collagen slurries, demonstrating that by monitoring the temperature within slurry
      during freezing, scaffold anisotropy with ice-templated scaffolds can be
      predicted. 

PMID- 24582234
TI  - Development of porous titanium for biomedical applications: A comparison between
      loose sintering and space-holder techniques.
AB  - One of the most important concerns in long-term prostheses is bone resorption as
      a result of the stress shielding due to stiffness mismatch between bone and
      implant. The aim of this study was to obtain porous titanium with stiffness
      values similar to that exhibited by cortical bone. Porous samples of commercial
      pure titanium grade-4 were obtained by following both loose-sintering processing
      and space-holder technique with NaCl between 40 and 70% in volume fraction. Both
      mechanical properties and porosity morphology were assessed. Young's modulus was
      measured using uniaxial compression testing, as well as ultrasound methodology.
      Complete characterization and mechanical testing results allowed us to determine
      some important findings: (i) optimal parameters for both processing routes; (ii)
      better mechanical response was obtained by using space-holder technique; (iii)
      pore geometry of loose sintering samples becomes more regular with increasing
      sintering temperature; in the case of the space-holder technique that trend was
      observed for decreasing volume fraction; (iv) most reliable Young's modulus
      measurements were achieved by ultrasound technique. 

PMID- 24582235
TI  - Regulation of physicochemical properties, osteogenesis activity, and fibroblast
      growth factor-2 release ability of beta-tricalcium phosphate for bone cement by
      calcium silicate.
AB  - beta-Tricalcium phosphate (beta-TCP) is an osteoconductive material. For this
      research we have combined it with a low degradation calcium silicate (CS) to
      enhance its bioactive and osteostimulative properties. To check its
      effectiveness, a series of beta-TCP/CS composites with different ratios were
      prepared to make new bioactive and biodegradable biocomposites for bone repair.
      Formation of bone-like apatite, the diametral tensile strength, and weight loss
      of composites were considered before and after immersion in simulated body fluid
      (SBF). In addition, we also examined the effects of fibroblast growth factor-2
      (FGF-2) released from beta-TCP/CS composites and in vitro human dental pulp cell
      (hDPC) and studied its behavior. The results showed that the apatite deposition
      ability of the beta-TCP/CS composites was enhanced as the CS content was
      increased. For composites with more than 50% CS contents, the samples were
      completely covered by a dense bone-like apatite layer. At the end of the
      immersion point, weight losses of 19%, 24%, 33%, 42%, and 51% were observed for
      the composites containing 0%, 30%, 50%, 70% and 100% beta-TCP cements,
      respectively. In vitro cell experiments show that the CS-rich composites promote
      human dental pulp cell (hDPC) proliferation and differentiation. However, when
      the CS quantity in the composite is less than 70%, the amount of cells and
      osteogenesis protein of hDPCs was stimulated by FGF-2 released from beta-TCP/CS
      composites. The combination of FGF-2 in degradation of beta-TCP and osteogenesis
      of CS gives a strong reason to believe that these calcium-based composite cements
      may prove to be promising bone repair materials. 

PMID- 24582236
TI  - The influence of bone quality on the biomechanical behavior of full-arch implant
      supported fixed prostheses.
AB  - We evaluated the influence of bone tissue type on stress distribution in full
      arch implant-supported fixed prostheses using a three-dimensional finite element
      analysis. Stresses in cortical and trabecular bones were also investigated.
      Edentulous mandible models with four implants inserted into the interforaminal
      region were constructed from different bone types: type 1 - compact bone; type 2 
      compact bone surrounding dense trabecular bone; type 3 - a thin layer of compact
      bone surrounding trabecular bone; and type 4 - low-quality trabecular bone. The
      mandible was restored with a full-arch implant-supported fixed prosthesis. A 100
      N oblique load was applied to the left lower first molar of the prosthesis. The
      maximum (sigmamax) and minimum (sigmamin) principal stress values were
      determined. The sigmamax in the type 4 cortical bone was 22.56% higher than that
      in the type 1 bone. The sigmamin values in the cortical bone were similar among
      all the bone types. For the superstructure, increases of 9.04% in the sigmamax
      and 11.74% in the sigmamin in G4 (type 4 bone) compared with G1 (type 1 bone)
      were observed. For the implants, the highest stress values were located in G4,
      and the lowest values were observed in G1. In the trabecular bone, the highest
      stress was generated in G1 and G2. In conclusion, the more compact bones (types 1
      and 2) are the most suitable for supporting full-arch implant-supported fixed
      prostheses, and poor bone quality may increase the risk of biological and
      mechanical failure. 

PMID- 24582237
TI  - Design and thermo-mechanical analysis of a new NiTi shape memory alloy fixing
      clip.
AB  - In this work, a new NiTi shape memory alloy (SMA) bone fixator is proposed.
      Thanks to the shape memory effect, this device does not need any external tool
      for the fixation, as the anchorage is obtained only by the self-accommodation of
      the clip during the parent transformation. Calorimetry and thermo-mechanical
      tests were used to evaluate the phase transformation temperatures and to estimate
      the forces generated both during the fixing surgical procedure and after the
      surgical operation. An application on animal anatomical sample was also
      performed; an appropriate mechanical tightness as well as a good handiness has
      been found. 

PMID- 24582238
TI  - Synthesis of an organic conductive porous material using starch aerogels as
      template for chronic invasive electrodes.
AB  - We report the development of an organic conducting mesoporous material, as coat
      for invasive electrodes, by a novel methodology based on the use of starch
      aerogel as template. The poly(3,4-ethylenedioxythiophene) (PEDOT) aerogel was
      synthesized by polymerization of 3,4-ethylenedioxythiophene within a saturated
      starch aerogel with iron (III) p-toluenesulfonate (oxidizing agent) and
      subsequent removal of the polysaccharide template, followed by supercritical CO2
      drying. The chemical structure and oxidation state of the resulting material were
      studied by Raman spectroscopy. The morphology and surface properties of the
      obtained nanoporous material were investigated by scanning electron microscopy
      (SEM), micro computed tomography (MUCT) and nitrogen adsorption-desorption
      techniques. The composition and thermal behaviour were evaluated by energy
      dispersive spectroscopy (EDS) and thermogravimetric analysis (TGA) respectively.
      A preliminary biocompatibility test verified the non-cytotoxic effects of the
      PEDOT aerogel. The large surface area and wide pore size distribution of the
      PEDOT conductive aerogel, along with its electrical properties, enable it to be
      used as extracellular matrix scaffold for biomedical applications. 

PMID- 24582239
TI  - Gelatin-PMVE/MA composite scaffold promotes expansion of embryonic stem cells.
AB  - We introduce a new composite scaffold of gelatin and polymethyl vinyl ether-alt
      maleic anhydride (PMVE/MA) for expansion of embryonic stem cells (ESCs) in an in
      vitro environment. To optimize the scaffold, we prepared a gelatin scaffold (G)
      and three composite scaffolds namely GP-1, GP-2, and GP-3 with varying PMVE/MA
      concentrations (0.2-1%) and characterized them by scanning electron microscopy
      (SEM), swelling study, compression testing and FTIR. SEM micrographs revealed
      interconnected porous structure in all the scaffolds. The permissible hemolysis
      ratio and activation of platelets by scaffolds confirmed the hemocompatibility of
      scaffolds. Initial biocompatibility assessment of scaffolds was conducted using
      hepatocarcinoma (Hep G2) cells and adhesion, proliferation and infiltration of
      Hep G2 cells in depth of scaffolds were observed, proving the scaffold's
      biocompatibility. Further Oct4B2 mouse embryonic stem cells (mESCs), which harbor
      a green fluorescence protein transgene under regulatory control of the Oct4
      promotor, were examined for expansion on scaffolds with MTT assay. The GP-2
      scaffold demonstrated the best cell proliferation and was further explored for
      ESC adherence and infiltration in depth (SEM and confocal), and pluripotent state
      of mESCs was assessed with the expression of Oct4-GFP and stage-specific
      embryonic antigen-1 (SSEA-1). This study reports the first demonstration of
      biocompatibility of gelatin-PMVE/MA composite scaffold and presents this scaffold
      as a promising candidate for embryonic stem cell based tissue engineering. 

PMID- 24582240
TI  - Synthesis and characterization of xanthan-hydroxyapatite nanocomposites for
      cellular uptake.
AB  - In this work xanthan-nanohydroxyapatite (XnHAp) and its equivalent strontium
      substituted (XnHApSr) were synthesized by the precipitation of nanohydroxyapatite
      in xanthan aqueous solution, characterized and compared to conventional
      hydroxyapatite particles (HAp). XnHAp and XnHApSr were less crystalline than HAp,
      as revealed by X-ray diffraction. Xanthan chains enriched the surface of XnHAp
      and XnHApSr particles, increasing the zeta potential values from -(7+/-1)mV,
      determined for HAp, to -(17+/-3)mV and -(25+/-3)mV, respectively. This effect led
      to high colloidal stability of XnHAp and XnHApSr dispersions and acicular
      particles (140+/-10)nm long and (8+/-2)nm wide, as determined by scanning
      electron microscopy and atomic force microscopy. XnHAp and XnHApSr particles were
      added to xanthan hydrogels to produce compatible nanocomposites (XCA/XnHAp and
      XCA/XnHApSr). Dried nanocomposites presented surface energy, Young's modulus and
      stress at break values comparable to those determined for bare xanthan matrix.
      Moreover, adding XnHAp or XnHApSr nanoparticles to xanthan hydrogel did not
      influence its porous morphology, gel content and swelling ratio. XCA/XnHAp and
      XCA/XnHApSr composites proved to be suitable for osteoblast growth and
      particularly XCA/XnHapSr composites induced higher alkaline phosphatase activity.

PMID- 24582241
TI  - Contribution of beta' and beta precipitates to hardening in as-solutionized Ag
      20Pd-12Au-14.5Cu alloys for dental prosthesis applications.
AB  - Dental Ag-20Pd-12Au-14.5Cu alloys exhibit a unique hardening behavior, which the
      mechanical strengths enhance significantly which enhances the mechanical strength
      significantly after high-temperature (1123K) solution treatment without aging
      treatment. The mechanism of the unique hardening is not clear. The contribution
      of two precipitates (beta' and beta phases) to the unique hardening behavior in
      the as-solutionized Ag-20Pd-12Au-14.5Cu alloys was investigated. In addition, the
      chemical composition of the beta' phase was investigated. The fine beta' phase
      densely precipitates in a matrix. The beta' phase (semi-coherent precipitate),
      which causes lattice strain, contributes greatly to the unique hardening
      behavior. On the other hand, the coarse beta phase sparsely precipitates in the
      matrix. The contribution of the beta phase (incoherent precipitate), which does
      not cause lattice strain, is small. The chemical composition of the beta' phase
      was determined. This study reveals that the fine beta' phase precipitated by high
      temperature solution treatment leads to the unique hardening behavior in dental
      Ag-20Pd-12Au-14.5Cu alloys in the viewpoints of the lattice strain contrast and
      interface coherency. It is expected to make the heat treatment process more
      practical for hardening. The determined chemical composition of beta' phase would
      be helpful to study an unknown formation process of beta' phase. 

PMID- 24582243
TI  - Incorporation of Ca and P on anodized titanium surface: Effect of high current
      density.
AB  - This study systematically evaluated the surface and corrosion characteristics of
      commercially pure titanium (grade 2) modified by plasma electrolytic oxidation
      (PEO) with high current density. The anodization process was carried out
      galvanostatically (constant current density) using a solution containing calcium
      glycerophosphate (0.02mol/L) and calcium acetate (0.15mol/L). The current
      densities applied were 400, 700, 1000 and 1200mA/cm(2) for a period of 15s.
      Composition, crystalline structure, morphology, roughness, wettability and "in
      vitro" bioactivity test in SBF of the anodized layer were evaluated by X-ray
      diffraction, scanning electron microscopy, energy dispersive spectroscopy,
      profilometry and contact angle measurements. Corrosion properties were evaluated
      by open circuit potential, electrochemical impedance spectroscopy (EIS) and
      potentiodynamic polarization measurements. The results show that the TiO2 oxide
      layers present an increase of thickness, porosity, roughness, wettability, Ca/P
      ratio, and bioactivity, with the applied current density up to 1000mA/cm(2).
      Corrosion resistance also increases with applied current density. It is observed
      that for 1200mA/cm(2), there is a degradation of the oxide layer. In general, the
      results suggest that the anodized TiO2 layer with better properties is formed
      with an applied current of 1000mA/cm(2). 

PMID- 24582242
TI  - Simultaneous bactericidal and osteogenic effect of nanoparticulate calcium
      phosphate powders loaded with clindamycin on osteoblasts infected with
      Staphylococcus aureus.
AB  - Staphylococcus aureus internalized by bone cells and shielded from the immune
      system provides a reservoir of bacteria in recurring osteomyelitis. Its targeting
      by the antibiotic therapy may thus be more relevant for treating chronic bone
      infection than eliminating only the pathogens colonizing the bone matrix.
      Assessed was the combined osteogenic and antibacterial effect of clindamycin
      loaded calcium phosphate nanoparticles of different monophasic compositions on co
      cultures comprising osteoblasts infected with S. aureus. Antibiotic-carrying
      particles were internalized by osteoblasts and minimized the concentration of
      intracellular bacteria. In vitro treatments of the infected cells, however, could
      not prevent cell necrosis due to the formation of toxic byproducts of the
      degradation of the bacterium. Antibiotic-loaded particles had a positive
      morphological effect on osteoblasts per se, without reducing their viability,
      alongside stimulating the upregulation of expression of different bone growth
      markers in infected osteoblasts to a higher degree than achieved during the
      treatment with antibiotic only. 

PMID- 24582244
TI  - Silk fibroin porous scaffolds for nucleus pulposus tissue engineering.
AB  - Intervertebral discs (IVDs) are structurally complex tissue that hold the
      vertebrae together and provide mobility to spine. The nucleus pulposus (NP)
      degeneration often results in degenerative IVD disease that is one of the most
      common causes of back and neck pain. Tissue engineered nucleus pulposus offers an
      alternative approach to regain the function of the degenerative IVD. The aim of
      this study is to determine the feasibility of porous silk fibroin (SF) scaffolds
      fabricated by paraffin-sphere-leaching methods with freeze-drying in the
      application of nucleus pulposus regeneration. The prepared scaffold possessed
      high porosity of 92.38+/-5.12% and pore size of 165.00+/-8.25MUm as well as high
      pore interconnectivity and appropriate mechanical properties. Rabbit NP cells
      were seeded and cultured on the SF scaffolds. Scanning electron microscopy,
      histology, biochemical assays and mechanical tests revealed that the porous
      scaffolds could provide an appropriate microstructure and environment to support
      adhesion, proliferation and infiltration of NP cells in vitro as well as the
      generation of extracellular matrix. The NP cell-scaffold construction could be
      preliminarily formed after subcutaneously implanted in a nude mice model. In
      conclusion, The SF porous scaffold offers a potential candidate for tissue
      engineered NP tissue. 

PMID- 24582245
TI  - Ultra-fast laser microprocessing of medical polymers for cell engineering
      applications.
AB  - Picosecond laser micromachining technology (PLM) has been employed as a tool for
      the fabrication of 3D structured substrates. These substrates have been used as
      supports in the in vitro study of the effect of substrate topography on cell
      behavior. Different micropatterns were PLM-generated on polystyrene (PS) and poly
      L-lactide (PLLA) and employed to study cellular proliferation and morphology of
      breast cancer cells. The laser-induced microstructures included parallel lines of
      comparable width to that of a single cell (which in this case is roughly 20MUm),
      and the fabrication of square-like compartments of a much larger area than a
      single cell (250,000MUm(2)). The results obtained from this in vitro study showed
      that though the laser treatment altered substrate roughness, it did not
      noticeably affect the adhesion and proliferation of the breast cancer cells.
      However, pattern direction directly affected cell proliferation, leading to a
      guided growth of cell clusters along the pattern direction. When cultured in
      square-like compartments, cells remained confined inside these for eleven
      incubation days. According to these results, laser micromachining with ultra
      short laser pulses is a suitable method to directly modify the cell
      microenvironment in order to induce a predefined cellular behavior and to study
      the effect of the physical microenvironment on cell proliferation. 

PMID- 24582246
TI  - Phosphate-based glass fiber vs. bulk glass: Change in fiber optical response to
      probe in vitro glass reactivity.
AB  - This paper investigates the effect of fiber drawing on the thermal and structural
      properties as well as on the glass reactivity of a phosphate glass in
      tris(hydroxymethyl)aminomethane-buffered (TRIS) solution and simulated body fluid
      (SBF). The changes induced in the thermal properties suggest that the fiber
      drawing process leads to a weakening and probable re-orientation of the POP
      bonds. Whereas the fiber drawing did not significantly impact the release of P
      and Ca, an increase in the release of Na into the solution was noticed. This was
      probably due to small structural reorientations occurring during the fiber
      drawing process and to a slight diffusion of Na to the fiber surface. Both the
      powders from the bulk and the glass fibers formed a Ca-P surface layer when
      immersed in SBF and TRIS. The layer thickness was higher in the calcium and
      phosphate supersaturated SBF than in TRIS. This paper for the first time presents
      the in vitro reactivity and optical response of a phosphate-based bioactive glass
      (PBG) fiber when immersed in SBF. The light intensity remained constant for the
      first 48h after which a decrease with three distinct slopes was observed: the
      first decrease between 48 and 200h of immersion could be correlated to the
      formation of the Ca-P layer at the fiber surface. After this a faster decrease in
      light transmission was observed from 200 to ~425h in SBF. SEM analysis suggested
      that after 200h, the surface of the fiber was fully covered by a thin Ca-P layer
      which is likely to scatter light. For immersion times longer than ~425h, the
      thickness of the Ca-P layer increased and thus acted as a barrier to the
      dissolution process limiting further reduction in light transmission. The
      tracking of light transmission through the PBG fiber allowed monitoring of the
      fiber dissolution in vitro. These results are essential in developing new
      bioactive fiber sensors that can be used to monitor bioresponse in situ. 

PMID- 24582247
TI  - Mechanical behavior of three nickel-titanium rotary files: A comparison of
      numerical simulation with bending and torsion tests.
AB  - AIM: To assess the flexibility and torsional stiffness of three nickel-titanium
      rotary instruments by finite element analysis and compare the numerical results
      with the experiment. METHODOLOGY: Mtwo (VDW, Munich, Germany) and RaCe (FKG
      Dentaire, La-Chaux-de-Fonds, Switzerland) size 25, .06 taper (0.25-mm tip
      diameter, 0.06% conicity) and PTU F1 (Dentsply Maillefer, Ballaigues,
      Switzerland) instruments were selected for this study. Experimental tests to
      assess the flexibility and torsional stiffness of the files were performed
      according to specification ISO 3630-1. Geometric models for finite element
      analysis were obtained by micro-CT scanning. Boundary conditions for the
      numerical analysis were based on the specification ISO 3630-1. RESULTS: A good
      agreement between the simulation and the experiment moment-displacement curves
      was found for the three types of instruments studied. RaCe exhibited the highest
      flexibility and PTU presented the highest torsional stiffness. Maximum values of
      von Mises stress were found for the PTU F1 file (1185MPa) under bending, whereas
      the values of von Mises stress for the three instruments were quite similar under
      torsion. The stress patterns proved to be different in Mtwo under bending,
      according to the displacement orientation. CONCLUSIONS: The favorable agreement
      found between simulation and experiment for the three types of instruments
      studied confirmed the potential of the numerical method to assess the mechanical
      behavior of endodontic instruments. Thus, a methodology is established to predict
      the failure of the instruments under bending and torsion.

PMID- 24582248
TI  - Facile stripping voltammetric determination of haloperidol using a high
      performance magnetite/carbon nanotube paste electrode in pharmaceutical and
      biological samples.
AB  - Multi-walled carbon nanotubes decorated with Fe3O4 nanoparticles were prepared to
      construct a novel sensor for the determination of haloperidol (Hp) by
      voltammetric methods. The morphology and properties of electrode surface were
      characterized by scanning electron microscopy (SEM) and electrochemical impedance
      spectroscopy. This modified sensor was used as a selective electrochemical sensor
      for the determination of trace amounts of Hp. The peak currents of differential
      pulse and square wave voltammograms of Hp increased linearly with its
      concentration in the ranges of 1.2*10(-3)-0.52 and 6.5*10(-4)-0.52MUmol L(-1),
      respectively. The detection limits for Hp were 7.02*10(-4) and 1.33*10(-4)MUmol
      L(-1) for differential pulse and square wave voltammetric methods, respectively.
      The results show that the combination of multi-walled carbon nanotubes and Fe3O4
      nanoparticles causes a dramatic enhancement in the sensitivity of Hp
      quantification. This sensor was successfully applied to determine Hp in
      pharmaceutical samples and biological fluids. The fabricated electrode showed
      excellent reproducibility, repeatability and stability.

PMID- 24582249
TI  - pH- and thermo-responsive microcontainers as potential drug delivery systems:
      Morphological characteristic, release and cytotoxicity studies.
AB  - Polymeric pH- and thermo-sensitive microcontainers (MCs) were developed as a
      potential drug delivery system for cancer therapy. It is well known that cancer
      cells exhibit notable characteristics such as acidic pH due to glycolytic cycle
      and higher temperature due to their higher proliferation rate. Based on these
      characteristics, we constructed a dual pH- and thermo-sensitive material for
      specific drug release on the pathological tissue. The MC's fabrication is based
      on a two-step procedure, in which, the first step involves the core synthesis and
      the second one is related to the shell formation. The core consists of
      poly(methyl methacrylate (PMMA), while the shell consists of PMMA,
      poly(isopropylacrylamide), poly(acrylic acid) and poly(divinylbenzene). Three
      different types of MCs were synthesized based on the seed polymerization method.
      The synthesized MCs were characterized structurally by Fourier transform infrared
      and morphologically by scanning electron microscopy. Dynamic light scattering was
      also used to study their behavior in aqueous solution under different pH and
      temperature conditions. For the loading and release study, the anthracycline drug
      daunorubicin (DNR) was used as a model drug, and its release properties were
      evaluated under different pH and thermo-conditions. Cytotoxicity studies were
      also carried out against MCF-7 breast cancer and 3T3 mouse embryonic fibroblast
      cells. According to our results, the synthesized microcontainers present desired
      pH and thermo behavior and can be applied in drug delivery systems. It is worth
      mentioning that the synthesized microcontainers which incorporated the drug DNR
      exhibit higher toxicity than the free drug. 

PMID- 24582250
TI  - Graphene oxide based magnetic nanocomposites for efficient treatment of breast
      cancer.
AB  - The present work reports a simple one step synthesis of nanoscale graphene oxide
      magnetic composites (GO-IO) using ferrofluid (GO-IOF). The obtained GO-IO were
      compared with GO-IO obtained from in situ (GO-IOI) methods. Anastrozole (ANS) was
      loaded on the GO-IOI and GO-IOF via simple stirring method to form GO-IOA and GO
      IOFA respectively. These GO-IO prepared by two techniques were characterized
      using spectroscopic techniques and vibrating sample magnetometer (VSM) analysis.
      Particle size and potential were measured using Malvern Zetasizer. Scanning
      electron microscopy (SEM) was used for studying the surface morphology of GO-IO,
      and in addition to this elemental analysis was also performed for confirming the
      presence of iron. The cell viability assay was carried out using the MCF-7 cell
      line. It revealed that GO-IOFA had reasonably high cytotoxicity (49.7%) compared
      to GO (13.1%), ANS (16.6), GO-IOI (13%), GO-IOF (13.6) and GO-IOIA (18.34%).
      Both, GO-IOIA and GO-IOFA showed improved cytotoxicity when compared with pure
      ANS. GO-IOF were found to exhibit superior magnetic activity due to higher iron
      content along with smaller particle size and higher loading efficiency compared
      to GO-IOI. The overall effect suggests that GO-IO can be utilized as efficient
      carriers for the loading of chemotherapeutic agents. 

PMID- 24582251
TI  - Hydrothermal synthesis and characterization of Si and Sr co-substituted
      hydroxyapatite nanowires using strontium containing calcium silicate as
      precursors.
AB  - In the absence of any organic surfactants and solvents, the silicon (Si) and
      strontium (Sr) co-substituted hydroxyapatite [Ca10(PO4)6(OH)2, Si/Sr-HAp]
      nanowires were synthesized via hydrothermal treatment of the Sr-containing
      calcium silicate (Sr-CS) powders as the precursors in trisodium phosphate
      (Na3PO4) aqueous solution. The morphology, phase, chemical compositions, lattice
      constants and the degradability of the products were characterized. The Si/Sr-HAp
      nanowires with diameter of about 60nm and up to 2MUm in length were obtained
      after hydrothermal treatment of the Sr-CS precursors. The Sr and Si substitution
      amount of the HAp nanowires could be well regulated by facile tailoring the Sr
      substitution level of the precursors and the reaction ratio of the
      precursor/solution, respectively. The SiO4 tetrahedra and Sr(2+) ions occupied
      the crystal sites of the HAp, and the lattice constants increased apparently with
      the increase of the substitution amount. EDS mapping also suggested the uniform
      distribution of Si and Sr in the synthetic nanowires. Moreover, the Si/Sr
      substitution apparently improved the degradability of the HAp materials. Our
      study suggested that the precursor transformation method provided a facile
      approach to synthesize the Si/Sr co-substituted HAp nanowires with controllable
      substitution amount, and the synthetic Si/Sr-HAp nanowires might be used as
      bioactive materials for hard tissue regeneration applications. 

PMID- 24582252
TI  - Tribological properties of Zr61Ti2Cu25Al12 bulk metallic glass under simulated
      physiological conditions.
AB  - In this work, wear resistance of a Zr61Ti2Cu25Al12 (ZT1) bulk metallic glass
      (BMG) in dry-sliding and simulated physiological media was investigated using
      ball-on-flat tribological approach and Si3N4 ball as counterpart. It was
      indicated that wear resistance of the BMG in air and deionized water is superior
      to Ti6Al4V alloy but inferior to 316L stainless steel (316L SS) and Co28Cr6Mo
      (CoCrMo) alloy. However, under simulated physiological media such as phosphate
      buffered solution (PBS) and Dulbecco's modified Eagle medium with 10vol.% fetal
      bovine serum (DMEM+FBS), the ZT1 BMG exhibits decreased wear resistance in
      comparison with the Ti6Al4V, 316L SS and CoCrMo. This is probably associated with
      its moderate pitting corrosion resistance in the medium containing chloride ions.
      The presence of protein in the solution has a significant effect to ruin pitting
      resistance of the BMG, then causing more severe wear damage. Under the dry-wear
      condition, abrasive wear is a predominant wear mechanism for the ZT1, whereas
      under deionized water, deterioration induced by abrasive wear can be mitigated.
      In simulated physiological media, wear deterioration is a typical tribocorrosion
      controlled by synergistic effects of the abrasive and corrosive wear. For the
      four investigated metals, wear resistance does not exhibit distinct correlation
      with hardness, whereas the material with high Young's modulus possesses better
      wear resistance. 

PMID- 24582253
TI  - Interaction of progenitor bone cells with different surface modifications of
      titanium implant.
AB  - Changes in the physical and chemical properties of Ti surfaces can be attributed
      to cell performance, which improves surface biocompatibility. The cell
      proliferation, mineralization ability, and gene expression of progenitor bone
      cells (D1 cell) were compared on five different Ti surfaces, namely, mechanical
      grinding (M), electrochemical modification through potentiostatic anodization
      (ECH), sandblasting and acid etching (SLA), sandblasting, hydrogen peroxide
      treatment, and heating (SAOH), and sandblasting, alkali heating, and etching
      (SMART). SAOH treatment produced the most hydrophilic surface, whereas SLA
      produced the most hydrophobic surface. Cell activity indicated that SLA and SMART
      produced significantly rougher surfaces and promoted D1 cell attachment within 1
      day of culturing, whereas SAOH treatment produced moderate roughness (Ra=1.26MUm)
      and accelerated the D1 cell proliferation up to 7 days after culturing. The ECH
      surface significantly promoted alkaline phosphatase (ALP) expression and
      osteocalcin (OCN) secretion in the D1 cells compared with the other surface
      groups. The ECH and SMART-treated Ti surfaces resulted in maximum ALP and OCN
      expressions during the D1 cell culture. SLA, SAOH, and SMART substrate surfaces
      were rougher and exhibited better cell metabolic responses during the early stage
      of cell attachment, proliferation, and morphologic expressions within 1 day of D1
      cell culture. The D1 cells cultured on the ECH and SMART substrates exhibited
      higher differentiation, and higher ALP and OCN expressions after 10 days of
      culture. Thus, the ECH and SMART treatments promote better ability of cell
      mineralization in vitro, which demonstrate their great potential for clinical
      use.

PMID- 24582254
TI  - Natural polyhydroxyalkanoate-gold nanocomposite based biosensor for detection of
      antimalarial drug artemisinin.
AB  - The worrisome trend of antimalarial resistance has already highlighted the
      importance of artemisinin as a potent antimalarial agent. The current
      investigation aimed at fabricating a biosensor based on natural polymer
      polyhydroxyalkanoate-gold nanoparticle composite mounting on an indium-tin oxide
      glass plate for the analysis of artemisinin. The biosensor was fabricated using
      an adsorbing horse-radish peroxidase enzyme on the electrode surface for which
      cyclic voltammetry was used to monitor the electro-catalytic reduction of
      artemisinin under diffusion controlled conditions. Electrochemical interfacial
      properties and immobilization of enzyme onto a polyhydroxyalkanoate-gold
      nanoparticle film were evaluated, and confirmed by cyclic voltammetry,
      electrochemical impedance spectroscopy and scanning electron microscopy. The
      differential pulse voltammetric peak current for artemisinin was increased
      linearly (concentration range of 0.01-0.08MUg mL(-1)) with sensitivity of
      0.26MUAMUg mL(-1). The greater sensitivity of the fabricated biosensor to
      artemisinin (optimum limits of detection were 0.0035MUg mL(-1) and 0.0036MUg mL(
      1) in bulk and spiked human serum, respectively) could be of much aid in medical
      diagnosis.

PMID- 24582255
TI  - Molecularly imprinted polymer based electrochemical detection of L-cysteine at
      carbon paste electrode.
AB  - A methacrylic acid (MAA) based molecularly imprinted polymer (MIP) modified
      carbon paste electrode (CPE) was developed for electrochemical detection of L
      cysteine (Cys). Characterisation of MIP was done with FTIR and the modified
      electrode with cyclic voltammetry (CV) and differential pulse voltammetry (DPV).
      CV, DPV and impedance analysis demonstrated that the modified electrode is
      responsive towards the target molecule. The optimum percentage composition of MIP
      for MIP/CPE and the effect of pH towards the electrode response for Cys were
      studied. The detection of Cys in the range of 2*10(-8) to 18*10(-8)M at MIP/CPE
      was monitored by DPV with a limit of detection of 9.6nM and R(2) of 0.9974. Also,
      various physiological interferents such as ascorbic acid, L-tryptophan, D
      glucose, D-cysteine and L-cysteine were found to have little effect on DPV
      response at MIP/CPE. The utility of the electrode was proved by the effective
      detection of Cys from tap water and human blood plasma samples with reproducible
      results. 

PMID- 24582256
TI  - Modeling of the reticulation kinetics of alginate/pluronic blends for biomedical
      applications.
AB  - In this work, blends of alginate/pluronic (F127) for biomedical applications were
      investigated. In particular, the kinetics of alginate chain reticulation by
      bivalent cations was studied by experimental and modeling approaches. Two kinds
      of sodium alginate were tested to obtain hard gel films. The thicknesses of the
      reticulated alginate films were measured as function of the exposure time and of
      the reticulating copper (Cu(2+)) solution concentration. The kinetics was
      described by a proper model able to reproduce the experimental data. The model
      parameters, evaluated based on the measurements of thicknesses as function of
      Cu(2+) concentration and exposure time, were further validated by comparing the
      prediction of the model with another set of independent measurement; here, the
      depletion of Cu(2+) ions in the conditioning solution above the reacting gel is
      measured as function of time. The tuned model could be used in the description of
      the future applications of the blends. 

PMID- 24582258
TI  - Nickel (II) incorporated AlPO-5 modified carbon paste electrode for determination
      of thioridazine in human serum.
AB  - In this approach, synthesis of nickel (II) incorporated aluminophosphate (NiAlPO
      5) was performed by using hydrothermal method. The diffuse reflectance
      spectroscopy (DRS), scanning electron microscopy (SEM), and Fourier transform
      infrared spectroscopy (FTIR) techniques were applied in order to characterize
      synthesized compounds. The NiAlPO-5 was used as a modifier in carbon paste
      electrode for the selective determination of thioridazine which is an
      antidepressant drug. This research is the first example of an aluminophosphate
      being employed in electroanalysis. The effective catalytic role of the modified
      electrode toward thioridazine oxidation can be attributed to the electrocatalytic
      activity of nickel (II) in the aluminaphosphate matrix. In addition, NiAlPO-5 has
      unique properties such as the high specific surface area which increases the
      electron transfer of thioridazine. The effects of varying the percentage of
      modifier, pH and potential sweep rate on the electrode response were
      investigated. Differential pulse voltammetry was used for quantitative
      determination as a sensitive method. A dynamic linear range was obtained in the
      range of 1.0*10(-7)-1.0*10(-5)mol L(-1). The determination of thioridazine in
      real samples such as commercial tablets and human serum was demonstrated.

PMID- 24582257
TI  - Tantalum coating on TiO2 nanotubes induces superior rate of matrix mineralization
      and osteofunctionality in human osteoblasts.
AB  - Nanostructured surface geometries have been the focus of a multitude of recent
      biomaterial research, and exciting findings have been published. However, only a
      few publications have directly compared nanostructures of various surface
      chemistries. The work herein directly compares the response of human osteoblast
      cells to surfaces of identical nanotube geometries with two well-known orthopedic
      biomaterials: titanium oxide (TiO2) and tantalum (Ta). The results reveal that
      the Ta surface chemistry on the nanotube architecture enhances alkaline
      phosphatase activity, and promotes a ~30% faster rate of matrix mineralization
      and bone-nodule formation when compared to results on bare TiO2 nanotubes. This
      study implies that unique combinations of surface chemistry and nanostructure may
      influence cell behavior due to distinctive physico-chemical properties. These
      findings are of paramount importance to the orthopedics field for understanding
      cell behavior in response to subtle alterations in nanostructure and surface
      chemistry, and will enable further insight into the complex manipulation of
      biomaterial surfaces. With increased focus in the field of orthopedic materials
      research on nanostructured surfaces, this study emphasizes the need for careful
      and systematic review of variations in surface chemistry in concurrence with
      nanotopographical changes. 

PMID- 24582260
TI  - Antibacterial, kinetics and bacteriolytic properties of silver(I)
      pyridinedicarboxylate compounds.
AB  - Antibacterial properties of silver(I)-pyridinedicarboxylate compounds (with
      Pyridine-2,3-dicarboxylic(Lutidinic acid), pyridine-2,4-dicarboxylic (Quinolinic
      acid) and pyridine-2,5-dicarboxylic (Isocinchomeronic acid)) were studied against
      Escherichia coli, Listeria monocytogenes (ISP-65-08), Salmonella typhi and
      Staphylococcus aureus (ATCC 25923) using kinetics of grown inhibition, viability
      assays, minimum inhibitory concentration and optical microscopy. The 3 silver
      compounds were tested toward UV-radiation in order to characterize their light
      insensitivity for potential medical devices: UV-radiation curable polymers.
      Photophysical measurements show remarkable differences toward UV-radiation, which
      were explained based on their polymeric structures with multiple nature bonds
      between pyridinedicarboxylic ligands and Ag(I) centers. We found a bacteriolytic
      effect and differences in the antibacterial efficiency depending on the structure
      of the complexes and the nature of AgX (X=oxygen and nitrogen) bonds:
      AgQuinol>AgLutidin>AgIsocinchom. 

PMID- 24582259
TI  - Synthesis of superparamagnetic iron oxide nanoparticles coated with a DDNP
      carboxyl derivative for in vitro magnetic resonance imaging of Alzheimer's
      disease.
AB  - Superparamagnetic iron oxide nanoparticles (SPIONs) have been proposed for use in
      magnetic resonance imaging as versatile ultra-sensitive nanoprobes for
      Alzheimer's disease imaging. In this work, we synthetized an efficient contrast
      agent of Alzheimer's disease using 1,1-dicyano-2-[6-(dimethylamino)naphthalene-2
      yl]propene (DDNP) carboxyl derivative to functionalize the surface of SPIONs. The
      DDNP-SPIONs are prepared by conjugating DDNP carboxyl derivative to oleic acid
      treated SPIONs through ligand exchange. The structure, size distribution and
      magnetic property were identified by IR, TGA-DTA, XRD, TEM, Zetasizer Nano and
      VSM. TEM and Zetasizer Nano observations indicated that the DDNP-SPIONs are
      relatively mono-dispersed spherical distribution with an average size of 11.7nm.
      The DDNP-SPIONs were then further analyzed for their MRI relaxation properties
      using MR imaging and demonstrated high T2 relaxivity of 140.57s(-1)FemM(-1), and
      the vitro experiment that DDNP-SPIONs binding to beta-Amyloid aggregates were
      then investigated by fluorophotometry, the results showed that the combination
      had induced the fluorescence enhancement of the DDNP-SPIONs and displayed
      tremendous promise for use as a contrast agent of Alzheimer's disease in MRI. 

PMID- 24582261
TI  - Formation of nanostructured fluorapatite via microwave assisted solution
      combustion synthesis.
AB  - Fluorapatite (FA) has potential applications in dentistry and orthopedics, but
      its synthesis procedures are time consuming. The goal of the present study is to
      develop a quick microwave assisted solution combustion synthesis method (MASCS)
      for the production of FA particles. With this new processing, FA particles were
      successfully synthesized in minutes. Additionally, unique structures including
      nanotubes, hexagonal crystals, nanowhiskers, and plate agglomerates were prepared
      by controlling the solution composition and reaction time. In particular, the as
      synthesized FA nanotubes presented a "Y" shape inner channel along the crystal
      axis. It is supposed that the channel formation is caused by the crystal growth
      and removal of water soluble salts during processing. The as-synthesized FA
      nanotubes showed good cytocompatibility, the cells cultured with a higher FA
      concentration demonstrated greater growth rate. With this new and easily applied
      MASCS processing application, FA nanoparticles have increased potential in dental
      and orthopedic applications. 

PMID- 24582262
TI  - Influence of material properties upon immobilization of histidine-tagged protein
      on Ni-Co coated chip.
AB  - In protein research, protein microarray facilitates high-throughput study of
      protein abundance and function. An appropriate microarray surface that can be
      used to immobilize protein samples is a prerequisite for the investigation of
      molecular interactions. Ni-Co alloy coated protein microarray chip has been found
      to adsorb histidine-tagged proteins effectively based on the method of
      immobilized metal affinity chromatography. Due to the ingredient of bi-metallic
      elements, different electroplating conditions resulted in distinct binding
      affinities. Therefore, the influence of Ni-Co material properties on the
      immobilization of histidine-tagged protein was systematically investigated in
      this study. In the experiments, the contact angle measurement suggested that no
      strong relationship can be established between the wettability of chip surface
      and its corresponding protein immobilization. ESCA test demonstrated that the
      major ingredients of the Ni-Co alloy coated protein microarray chip were Ni and
      Co. In addition, the XRD test concluded that a Ni-Co protein chip that consists
      mostly of hcp lattice has better binding capability. SEM micrographs provide
      direct image evidence. These material tests summarize that the Ni-Co alloy coated
      protein microarray chip adsorbs His-tagged proteins through its surface
      morphology. Therefore, it can provide specific binding due to the affinity
      adsorption between the intermediate metals and the protein. 

PMID- 24582263
TI  - Titanium dioxide nanotube films: Preparation, characterization and
      electrochemical biosensitivity towards alkaline phosphatase.
AB  - Titania nanotubes (TNTs) were prepared by anodization on different substrates
      (titanium, Ti6Al4V and Ti6Al7Nb alloys) in ethylene glycol and glycerol. The
      influence of the applied potential and processing time on the nanotube diameter
      and length is analyzed. The as-formed nanotube layers are amorphous but they
      become crystalline when subjected to subsequent thermal treatment in air at 550
      degrees C; TNT layers grown on titanium and Ti6Al4V alloy substrates consist of
      anatase and rutile, while those grown on Ti6Al7Nb alloy consist only of anatase.
      The nanotube layers grown on Ti6Al7Nb alloy are less homogeneous, with
      supplementary islands of smaller diameter nanotubes, spread across the surface.
      Better adhesion and proliferation of osteoblasts was found for the nanotubes
      grown on all three substrates by comparison to an unprocessed titanium plate. The
      sensitivity towards bovine alkaline phosphatase was investigated mainly by
      electrochemical impedance spectroscopy in relation to the crystallinity, the
      diameter and the nature of the anodization electrolyte of the TNT/Ti samples. The
      measuring capacity of the annealed nanotubes of 50nm diameter grown in glycerol
      was demonstrated and the corresponding calibration curve was built for the
      concentration range of 0.005-0.1mg/mL. 

PMID- 24582264
TI  - Preparation and characterization of a sulindac sensor based on PVC/TOA-SUL
      membrane.
AB  - A potentiometric sulindac sensitive sensor based on tetraoctylammonium (Z)-5
      fluoro-2-methyl-1-[[p-(methylsulfinyl)phenyl]methylene]-1H-indene-3-acetate (TOA
      SUL) was described. The electrode responded with sensitivity of 57.5+/-1.6mV
      decade(-1) over the linear range 5*10(-5)-1*10(-2)mol L(-1) at pH6.0-9.0. It had
      the limit of detection 1.4*10(-5)mol L(-1), a fast response time of 13s and
      showed clear discrimination of sulindac ions from several inorganic and organic
      compounds and also amino acids. This electrode did not contain any inner
      solutions, so it was easy and comfortable to use. The proposed sensor was used to
      determine sulindac in clear solution and in urine sample solution.

PMID- 24582265
TI  - Photoinduced properties of nanocrystalline TiO2-anatase coating on Ti-based bone
      implants.
AB  - The paper reports on the photoinduced properties of hydrothermally treated (HT)
      titanium used for bone implants. The anatase coatings composed of 30-100nm
      anatase crystals exhibited high photocatalytic activity and good photo-induced
      wettability, reaching a superhydrophilic state, despite the larger crystal
      dimensions than the previously reported optimal ones. These properties are due to
      a suitable combination of surface texture, roughness, thickness, crystal
      morphology and particle size, which allowed the two independent photo-induced
      phenomena to occur simultaneously. The results on caffeine degradation by
      photocatalysis and the prolonged effect (up to two weeks) of photo-induced
      wettability in dark suggested a possible applicability of the HT anatase coatings
      as bacteria-repelling surfaces for body implants, in favor of a better
      osseointegration in vivo. 

PMID- 24582266
TI  - Fabrication and characterization of bioactive glass-ceramic using soda-lime
      silica waste glass.
AB  - Soda-lime-silica waste glass was used to synthesize a bioactive glass-ceramic
      through solid-state reactions. In comparison with the conventional route, that
      is, the melt-quenching and subsequent heat treatment, the present work is an
      economical technique. Structural and thermal properties of the samples were
      examined by X-ray diffraction (XRD) and differential thermal analysis (DTA). The
      in vitro test was utilized to assess the bioactivity level of the samples by
      Hanks' solution as simulated body fluid (SBF). Bioactivity assessment by atomic
      absorption spectroscopy (AAS) and scanning electron microscopy (SEM) was revealed
      that the samples with smaller amount of crystalline phase had a higher level of
      bioactivity. 

PMID- 24582267
TI  - In vitro embryo production in goats: Slaughterhouse and laparoscopic ovum pick up
      derived oocytes have different kinetics and requirements regarding maturation
      media.
AB  - A total of 3427 goat oocytes were used in this study to identify possible
      differences during in vitro embryo production from slaughterhouse or laparoscopic
      ovum pick up (LOPU) oocytes. In experiment 1, one complex, one semi-defined, and
      one simplified IVM media were compared using slaughterhouse oocytes. In
      experiment 2, we checked the effect of oocyte origin (slaughterhouse or LOPU) on
      the kinetics of maturation (18 vs. 22 vs. 26 hours) when submitted to semi
      defined or simplified media. In experiment 3, we determined the differences in
      embryo development between slaughterhouse and LOPU oocytes when submitted to both
      media and then to IVF or parthenogenetic activation (PA). Embryos from all groups
      were vitrified, and their viability evaluated in vitro after thawing. In
      experiment 1, no difference (P > 0.05) was detected among treatments for
      maturation rate (metaphase II [MII]; 88% on average), cleavage (72%), blastocyst
      from the initial number of cumulus oocyte complexes (46%) or from the cleaved
      ones (63%), hatching rate (69%), and the total number of blastomeres (187). In
      experiment 2, there was no difference of MII rate between slaughterhouse oocytes
      cultured for 18 or 22 hours, whereas the MII rate increased significantly (P <
      0.05) between 18 and 22 hours for LOPU oocytes in the simplified medium.
      Moreover, slaughterhouse oocytes cultured in simplified medium matured
      significantly faster than LOPU oocytes at 18 and 22 hours (P < 0.05). In
      experiment 3, cleavage rate was significantly greater (P < 0.001) in all four
      groups of embryos produced by PA than IVF. Interestingly, PA reached similar
      rates for slaughterhouse oocytes cultured in both media, but improved (P < 0.05)
      the cleavage rate of LOPU oocytes. Slaughterhouse oocytes had acceptable cleavage
      rate after IVF (~67%), whereas LOPU oocytes displayed a lower one (~38%), in
      contrast to cleavage after PA. The percentage of blastocysts in relation to
      cleaved embryos was not affected by the origin of the oocytes (P > 0.05).
      Therefore, slaughterhouse oocytes developed a greater proportion of blastocysts
      than LOPU ones, expressed as the percentage of total cumulus oocyte complexes
      entering to IVM. Vitrified-thawed blastocysts presented similar survival and
      hatching rates between the oocyte origin, media, or method of activation. In
      conclusion, slaughterhouse and LOPU derived oocytes may have different IVM
      kinetics and require different IVM and IVF conditions. Although the IVM and IVF
      systems still need improvements to enhance embryo yield, the in vitro development
      step is able to generate good quality embryos from LOPU-derived oocytes.

PMID- 24582268
TI  - Bone morphogenetic proteins in the bovine oviduct: differential expression of BMP
      5 in the isthmus during the estrous cycle.
AB  - Bone morphogenetic proteins (BMPs) play a crucial role in mammalian reproduction,
      but little is known about their expression and function in the oviduct, where
      preimplantation events take place. In the present study, messenger RNA (mRNA)
      expression of BMPs was examined by semiquantitative reverse transcription
      polymerase chain reaction (RT-PCR) in bovine oviduct epithelial cells obtained
      from ampulla and isthmus at different stages of the estrous cycle. Expression of
      BMP-2, -3, -4, -7, -10 and -15 mRNA was detected in epithelial cells of both
      anatomic regions, whereas BMP-5 mRNA was specifically expressed in isthmus
      epithelial cells throughout the estrous cycle. High expression levels for BMP-5
      and for BMP-2, -4, and -7 mRNA were observed during the preovulatory stage.
      Considering the region-specific gene expression of BMP-5, its protein
      localization in the oviduct and its presence in the oviductal fluid were
      evaluated by immunohistochemistry and Western blot analysis. BMP-5 protein
      staining was observed in isthmus sections with a more intense signal in the
      luminal epithelial cell layer. In addition, a 21 kDa protein corresponding to the
      BMP-5 mature monomeric form was detected in bovine oviductal fluid throughout the
      estrous cycle. In conclusion, these results demonstrate that different members of
      the BMP family are expressed in the bovine oviduct during the estrous cycle, and
      reveal that BMP-5 is differentially expressed in the isthmus. The expression of
      this factor in the oviduct epithelium and its presence in the luminal fluid
      suggest a possible action of BMP-5 as a new autocrine and/or paracrine regulator
      of the reproductive events that occur in the bovine oviductal environment.

PMID- 24582269
TI  - Molecular targeted therapy for early-stage non-small-cell lung cancer: will it
      increase the cure rate?
AB  - Non-small-cell lung cancer (NSCLC) represents approximately 85% of all lung
      cancer cases, with a world-wide annual incidence of around 1.3 million. Surgery
      remains the corner stone of treatment in early-stage NSCLC when feasible, and the
      addition of adjuvant cisplatin-based chemotherapy has improved these results in
      resected NSCLC patients. For those patients with non-metastatic NSCLC not
      suitable for complete surgical resection, chemotherapy plus radiotherapy remains
      the best treatment option. For patients with metastatic NSCLC, molecular targeted
      agents have become part of the therapeutic arsenal in recent years. However, to
      date no targeted agent has been approved for patients with early or locally
      advanced stages of NSCLC. Here, we review the rationale, literature and studies
      addressing the role of targeted agents used in the adjuvant setting or as part of
      chemoradiotherapy regimens. 

PMID- 24582270
TI  - Hip arthritis: colo-coxal fistula 25 years after sigmoidectomy.

PMID- 24582271
TI  - A recto-dural fistula.

PMID- 24582272
TI  - Stereotype endorsement, metacognitive capacity, and self-esteem as predictors of
      stigma resistance in persons with schizophrenia.
AB  - OBJECTIVE: While research continues to document the impact of internalized stigma
      among persons with schizophrenia, little is known about the factors which promote
      stigma resistance or the ability to recognize and reject stigma. This study aimed
      to replicate previous findings linking stigma resistance with lesser levels of
      depression and higher levels of self-esteem while also examining the extent to
      which other factors, including metacognitive capacity and positive and negative
      symptoms, are linked to the ability to resist stigma. METHOD: Participants were
      62 adults with schizophrenia-spectrum disorders who completed self-reports of
      stigma resistance, internalized stigma, self-esteem, and rater assessments of
      positive, negative, disorganization, and emotional discomfort symptoms, and
      metacognitive capacity. RESULTS: Stigma resistance was significantly correlated
      with lower levels of acceptance of stereotypes of mental illness, negative
      symptoms, and higher levels of metacognitive capacity, and self-esteem. A
      stepwise multiple regression revealed that acceptance of stereotypes of mental
      illness, metacognitive capacity, and self-esteem all uniquely contributed to
      greater levels of stigma resistance, accounting for 39% of the variance.
      CONCLUSION: Stigma resistance is related to, but not synonymous with,
      internalized stigma. Greater metacognitive capacity, better self-esteem, and
      fewer negative symptoms may be factors which facilitate stigma resistance.

PMID- 24582273
TI  - Prediction of major vascular events after stroke: the stroke prevention by
      aggressive reduction in cholesterol levels trial.
AB  - BACKGROUND: Identifying patients with recent stroke or transient ischemic attack
      (TIA) at high risk of major vascular events (MVEs; stroke, myocardial infarction,
      or vascular death) may help optimize the intensity of secondary preventive
      interventions. We evaluated the relationships between the baseline Framingham
      Coronary Risk Score (FCRS) and a novel risk prediction model and with the
      occurrence of MVEs after stroke or TIA in subjects enrolled in the Stroke
      Prevention by Aggressive Reduction in Cholesterol Level (SPARCL) trial. METHODS:
      Data from the 4731 subjects enrolled in the SPARCL study were analyzed. Hazard
      ratios (HRs) from Cox regression models were used to determine the risk of
      subsequent MVEs based on the FCRS predicting 20% or more 10-year coronary heart
      disease risk. The novel risk model was derived based on multivariable modeling
      with backward selection. Model discrimination (c-statistics) was assessed using
      the areas under the receiver operating characteristic curves. RESULTS: Of 3969
      subjects with complete data, 27% had a baseline FCRS of 20% or more. In
      multivariable analysis, an FCRS of 20% or more was associated with twice the risk
      of subsequent MVEs (HR = 1.92, 95% confidence interval [CI]: 1.63-2.27). The
      novel model based on a multivariable analysis included age (HR = 1.37, 95% CI:
      1.25-1.51 per 10 years), diabetes (HR = 1.82, 95% CI: 1.51-2.18), male sex (HR =
      1.35, 95% CI: 1.12-1.61), and an apolipoprotein (APO)-B/APO-A1 ratio (HR = 1.56,
      95% CI: 1.16-2.11). The c-statistic was .58 (95% CI: .55-.60) for the FCRS of 20%
      or more and .65 (95% CI: .63-.67) for the novel model. CONCLUSIONS: Both a
      baseline FCRS of 20% or more and a novel predictive model were associated with
      future MVEs in SPARCL trial subjects. The novel model needs to be validated, and
      the benefits of using either the FCRS or the novel model in clinical practice
      needs to be assessed.

PMID- 24582274
TI  - Isolated pelvic perfusion in irradiated unresectable recurrence of pelvic tumor:
      preliminary outcome and ongoing study.
AB  - The technique of isolated pelvic perfusion (IPP) using extracorporeal circulation
      is capable of delivering high dose chemotherapy in the pelvic cavity. This
      technique has improved over time, notably with the use of a G-suit placed and
      inflated above the iliac bifurcation to impede flow through percutaneous vascular
      routes. This approach is of potential value in patients with previously
      irradiated, locally advanced recurrences of cancer originating from the
      gynecological or gastrointestinal organs. Administration of tumor necrosis factor
      alpha (TNF-alpha) in combination with melphalan seems to provide response rates
      similar to those obtained in the technique of isolated extremity perfusion. A
      preliminary phase I study has shown promising results in terms of feasibility and
      response rates. A randomized study is currently underway to compare IPP to
      standard treatment in patients with unresectable recurrent pelvic tumors of
      gynecological or gastrointestinal origin. 

PMID- 24582275
TI  - Treatment of hepatic metastases of colorectal cancer by robotic stereotactic
      radiation (Cyberknife (r)).
AB  - Cyberknife((r)) is a dedicated stereotactic radiotherapy device. This new
      technology permits precise delivery of high dose gradient radiation therapy while
      sparing the surrounding organs at risk. Hepatic metastases of colorectal cancer
      (HMCRC) are an example of a lesion where treatment with Cyberknife((r)) is
      indicated because they are located in a radio-sensitive organ and curative
      treatment is based on focal eradication (resection, radiofrequency ablation,...).
      The local control rate at one year is reported to be 70 to 100% depending on the
      study. Tolerance is excellent with less than a 5% rate of acute grade 3 or 4 side
      effects (nausea, vomiting, gastro-duodenal ulcer). The specific hepatotoxicity of
      radiotherapy, so-called radiation-induced liver disease (RILD), was found in only
      one study. Candidates for stereotactic radiotherapy are patients in whom disease
      is controlled except for intrahepatic disease with 1-3 hepatic metastases <= 6 cm
      in size who have contraindications for surgery, a WHO stage <= 2, a volume of
      healthy liver >= 700 cm(3) and normal liver function. It is actually a very
      simple treatment that results in very good local control with few
      contraindications. Its place in the management strategy of liver metastases needs
      further clarification.

PMID- 24582276
TI  - Isolated hepatic perfusion: principles and results.
AB  - INTRODUCTION: Isolated hepatic perfusion allows the delivery of high dose
      chemotherapy while decreasing extra-hepatic toxicity, and is used mainly for
      patients with surgically unresectable liver tumors. PRINCIPLES: Vascular
      exclusion of the liver is performed after obtaining satisfactory hemodynamic
      tolerance, occasionally after cavocaval shunt and/or porto-systemic shunt.
      Perfusion entry can be arterial and/or portal while the exit is portal or caval.
      The perfusion circuit can be open or closed, using a circulation pump with or
      without oxygenation. The chemotherapy regimens used are high dose melphalan (with
      or without TNF-alpha), oxaliplatin, cisplatin and mitomycin, sometimes associated
      with moderate hyperthermia. The duration of perfusion ranges between 30 and 90
      minutes according to the different protocols used. A percutaneous technique with
      incomplete liver vascular exclusion is also possible. RESULTS: The larger series
      in the literature show a response rate (partial or complete stabilization)
      between 60 and 80%, with approximately 5% complete morphologic responses.
      Morbidity and mortality are 40 and 5%, respectively, including specific morbidity
      related to the perfusion procedure as well as to chemotherapy. CONCLUSION:
      Chemotherapy delivered through isolated hepatic perfusion is a new therapeutic
      alternative, still under development, and can be proposed to patients with
      surgically unresectable primary or secondary liver tumors within clinical trials.
      These results seem to be promising, but are still associated with a non
      negligible morbidity rate.

PMID- 24582277
TI  - Chemical constituents from aerial parts of Caryopteris incana and cytoprotective
      effects in human HepG2 cells.
AB  - An ethyl acetate fraction of the aerial parts of Caryopteris incana (Verbenaceae)
      showed potent cytoprotective effects against damage to HepG2 cells induced by
      tert-butylhydroperoxide (t-BHP). To search for hepatoprotective components of C.
      incana, various chromatographic separations of the ethyl acetate soluble fraction
      of C. incana led to isolation of three phenylpropanoid glycosides, 6'''-O
      feruloylincanoside D, 6'''-O-sinapoylincanoside D and caryopteroside, and two
      iridoid glycosides, incanides A and B, together with 17 known compounds.
      Structures of these compounds were determined by spectroscopic analyses. The
      absolute stereochemistry of the caryopteroside was established with the help of
      circular dichroism data and in comparison with literature data. All isolated
      substances were determined for their cytoprotective effects against t-BHP-induced
      toxicity in HepG2 cells. Among the tested compounds, 6'-O-caffeoylacteoside
      exhibited the most potent cytoprotective activity with an IC50 value of 0.8+/-0.1
      MUM against t-BHP-induced toxicity. Structure-activity relationships of the assay
      results indicated an important role of the catechol moiety in phenylpropanoid,
      iridoid and flavonoid derivatives in eliciting cytoprotective effects.

PMID- 24582278
TI  - Exogenously applied 24-epi brassinolide reduces lignification and alters cell
      wall carbohydrate biosynthesis in the secondary xylem of Liriodendron tulipifera.
AB  - The roles of brassinosteroids (BRs) in vasculature development have been
      implicated based on an analysis of Arabidopsis BR mutants and suspension cells of
      Zinnia elegans. However, the effects of BRs in vascular development of a woody
      species have not been demonstrated. In this study, 24-epi brassinolide (BL) was
      applied to the vascular cambium of a vertical stem of a 2-year-old Liriodendron,
      and the resulting chemical and anatomical phenotypes were characterized to
      uncover the roles of BRs in secondary xylem formation of a woody species. The
      growth in xylary cells was clearly promoted when treated with BL. Statistical
      analysis indicated that the length of both types of xylary cells (fiber and
      vessel elements) increased significantly after BL application. Histochemical
      analysis demonstrated that BL-induced growth promotion involved the acceleration
      of cell division and cell elongation. Histochemical and expression analysis of
      several lignin biosynthetic genes indicated that most genes in the
      phenylpropanoid pathway were significantly down-regulated in BL-treated stems
      compared to that in control stems. Chemical analysis of secondary xylem
      demonstrated that BL treatment induced significant modification in the cell wall
      carbohydrates, including biosynthesis of hemicellulose and cellulose.
      Lignocellulose crystallinity decreased significantly, and the hemicellulose
      composition changed with significant increases in galactan and arabinan. Thus, BL
      has regulatory roles in the biosynthesis and modification of secondary cell wall
      components and cell wall assembly during secondary xylem development in woody
      plants. 

PMID- 24582279
TI  - Adaptation of a commercial ELISA to determine the IgG avidity in sheep
      experimentally and naturally infected with Neospora caninum.
AB  - Recent reports indicate Neospora caninum has a possible role in causing abortions
      in sheep in New Zealand. Knowledge about the epidemiology of neosporosis in sheep
      is limited. This study aimed to adapt and validate a commercially available ELISA
      assay as an IgG avidity assay to discriminate between acute (primary and re
      inoculated) and chronic N. caninum infections in sheep. In addition, it was used
      to compare the antibody avidity values between lambs from ewes inoculated with N.
      caninum either during the pregnancy or in the previous year. The avidity assay
      was undertaken by using 6M urea for the first wash after incubation with the
      primary antibody in the commercial ELISA (Chekit* Neospora antibody test kit,
      IDEXX Laboratories, Australia). Sequential serum samples were obtained from naive
      ewes (n=16) experimentally inoculated with live N. caninum tachyzoites. All ewes
      were seropositive by two weeks post-inoculation and remained seropositive for 20
      weeks post-inoculation. There was a linear relationship between time after
      inoculation and avidity values (p<0.05) over the first 24 weeks. In Week 4, all
      animals had avidity values <35% and by Week 8, 8/16 animals had avidity values of
      >35%. These results suggest that an avidity value of <35% indicates a recent
      primary infection while a value of >35% is indicative of a chronic infection. The
      assay was then validated using samples from other groups of experimentally
      inoculated sheep as well as samples from naturally infected ewes. When comparing
      sample to positive ratio (S/P) and avidity values from lambs born from recently
      inoculated ewes with those from ewes inoculated the previous year and re
      inoculated in the current year, it was possible to differentiate the lambs at 2
      weeks of age. Lambs from recently inoculated ewes had low S/P and avidity values
      at 2 weeks of age which increased by 12 weeks of age. In comparison, lambs from
      re-inoculated ewes had high S/P and avidity values at 2 weeks of age, due to
      maternal antibody influence but values were similar to those from lambs that were
      born from recently inoculated ewes at 12 weeks of age. Avidity values for four
      naturally infected ewes were all >60% indicating chronic infection. These results
      suggest that the assay is able to discriminate between recent and chronic
      infection in sheep as well as able to differentiate lambs with maternal immunity
      compared to their own de novo immunity. As such it can be utilized to understand
      the kinetics of N. caninum infection in sheep. 

PMID- 24582280
TI  - The P75 neurotrophin receptor regulates proliferation of the human MG63
      osteoblast cell line.
AB  - The 75 kDa transmembrane protein, p75(NTR), is a marker of mesenchymal stem cells
      (MSCs). Isolated MSCs are capable of differentiating into osteoblasts, but the
      molecular function of p75(NTR) in MSCs and osteoblasts is poorly understood. The
      aim of this study was to examine the function of p75(NTR) in the human MG63
      osteoblast cell line compared to the murine MC3T3E-1 pre-osteoblast cell line.
      MG63 cells and MC3T3-E1 cells expressing exogenous p75(NTR) protein (denoted as
      p75-MG63 and p75GFP-E1, respectively) were generated to compare osteogenic
      differentiation and cell proliferation abilities. Overexpression of p75(NTR)
      induced alkaline phosphatase activity and the mRNA expression of osteoblast
      related genes such as osterix and bone sialoprotein in both p75-MG63 and p75GFP
      E1. Interestingly, exogenous p75(NTR) stimulated cell proliferation and cell
      cycle progression in p75GFP-E1, but not in p75-MG63. To elucidate any different
      effects of p75(NTR) expression on osteogenic differentiation and cell
      proliferation, we examined the mRNA expression of tropomyosin receptor kinase
      (trk) genes (trkA, trkB, trkC) and Nogo receptor (NgR), which are binding
      partners of p75(NTR). Although trkA, trkB, and trkC were detected in both p75
      MG63 and p75GFP-E1, only NgR was detected in p75-MG63. We then used the K252a
      inhibitor of the trks to identify the signaling pathway for osteogenic
      differentiation and cell proliferation. Inhibition of trks by K252a suppressed
      p75(NTR)-mediated osteogenic differentiation of p75GFP-E1, whereas deletion of
      the GDI domain in P75(NTR) from the p75-MG63 produced enhanced cell proliferation
      compared to p75-MG63. These results suggest that p75(NTR) signaling associated
      with trk receptors promotes both cell proliferation and osteoblast
      differentiation, but that p75(NTR)-mediated proliferation may be suppressed by
      signaling from the p75(NTR)/NgR complex.

PMID- 24582281
TI  - Efficacy of higher protein diets for long-term weight control. How to assess
      quality of randomized controlled trials?

PMID- 24582282
TI  - Concentrations of basic drugs in postmortem blood require careful evaluation.

PMID- 24582283
TI  - Survival from rabies encephalitis.
AB  - Rabies is a major public health problem in Asia and Africa, with nearly 60,000
      deaths every year, and represents a substantial economic burden. Neurologists
      frequently encounter atypical cases, and need to make informed decisions
      regarding diagnosis and management. No therapy has been shown to unequivocally
      improve survival in rabies till date. Despite the overwhelmingly fatal nature of
      this disease, a small number of patients have been reported to survive acute
      rabies encephalitis with varying degrees of neurological sequelae. This paper
      presents the eleventh documented case of survival from rabies, which developed
      after being bitten by a stray dog, albeit with severe neurological residua.
      Similar to patients in previous reports, this man demonstrated a robust immune
      response as indicated by peripheral viral clearance and very high serum and
      cerebrospinal fluid antibody titres. Immunologically-mediated virus clearance
      therefore appears to be a prerequisite for survival. A detailed review of
      previously reported survivors, as well as descriptions of the host response and
      viral clearance in human rabies, current therapy for this disease and future
      directions in improving the currently dismal prognosis are provided. 

PMID- 24582284
TI  - Blood pressure variability and stroke outcome in patients with internal carotid
      artery occlusion.
AB  - PURPOSE: The aim of this study was to evaluate the relationship between arterial
      blood pressure (BP) variability during the acute phase and the 3-month outcome in
      ischemic stroke patients with internal carotid artery (ICA) occlusion. METHODS:
      At least 10 BP measurements during the first 48 h after stroke onset were
      obtained in 89 patients with ICA occlusion. BP profile was described using
      various parameters: average of recordings, maximum (max), minimum (min),
      difference between max and min (max-min), standard deviation (SD) and coefficient
      of variation (CV) for both systolic and diastolic BP. Outcome at 3 months was
      defined using the modified Rankin Scale (mRS) score corrected for baseline stroke
      severity. RESULTS: Fifty-five patients had a good and 34 a poor outcome. Max
      values, max-min, SD and CV of both systolic and diastolic BP resulted
      significantly higher in patients with poor outcome compared to those with good
      outcome (p<0.05, multivariate adjusted model). CONCLUSIONS: In a cohort of acute
      ischemic stroke patients with ipsilateral ICA occlusion BP variability, assessed
      in the acute phase, was associated with poor clinical outcome. These preliminary
      exploratory findings are worthy of further study to be conducted to confirm or
      confute the role of BP variability in predicting stroke outcome. In order to
      obtain more comprehensive information, it would also be appropriate to consider
      the possibility of acquiring data related to the pathophysiology of stroke and to
      cerebral hemodynamic changes.

PMID- 24582285
TI  - Combined CMV- and HSV-1 brainstem encephalitis restricted to medulla oblongata.
AB  - We report a very rare case of a combined CMV- and HSV-1 isolated brainstem
      encephalitis restricted to medulla oblongata in a patient with advanced HIV
      disease. Neither limbic nor general ventricular involvement was detected on
      neuroimaging. The case highlights the importance of testing for HSV-1 and CMV in
      HIV-infected patients presenting with an isolated brainstem syndrome. 

PMID- 24582287
TI  - WITHDRAWN: Editorial of special issue Computing and Visualisation for
      Intravascular Imaging.
AB  - The Publisher regrets that this article is an accidental duplication of an
      article that has already been published,
      http://dx.doi.org/10.1016/j.compmedimag.2014.01.001. The duplicate article has
      therefore been withdrawn.

PMID- 24582286
TI  - Lysine biotinylation and methionine oxidation in the heat shock protein HSP60
      synergize in the elimination of reactive oxygen species in human cell cultures.
AB  - Previous studies suggest that the number of proteins containing covalently bound
      biotin is larger than previously thought. Here, we report the identity of some of
      these proteins. Using mass spectrometry, we discovered 108 novel biotinylation
      sites in the human embryonic kidney HEK293 cell proteome; members of the heat
      shock protein (HSP) superfamily were overrepresented among the novel biotinylated
      proteins. About half of the biotinylated proteins also displayed various degrees
      of methionine oxidation, which is known to play an important role in the defense
      against reactive oxygen species; for biotinylated HSPs, the percent of methionine
      sulfoxidation approached 100%. Protein structure analysis suggests that
      methionine sulfoxides localize in close physical proximity to the biotinylated
      lysines on the protein surface. Mass spectrometric analysis revealed that between
      one and five of the methionine residues in the C-terminal KEEKDPGMGAMGGMGGGMGGGMF
      motif are oxidized in HSP60. The likelihood of methionine sulfoxidation is higher
      if one of the adjacent lysine residues is biotinylated. Knockdown of HSP60 caused
      a 60% increase in the level of reactive oxygen species in fibroblasts cultured in
      biotin-sufficient medium. When HEK293 cells were transferred from biotin
      sufficient medium to biotin-free medium, the level of reactive oxygen species
      increased by >9 times compared with baseline controls and a time-response
      relationship was evident. High levels of methionine sulfoxidation coincided with
      cell cycle arrest in the G0/G1 and S phases in biotin-depleted cells. We conclude
      that biotinylation of lysines synergizes with sulfoxidation of methionines in
      heat shock proteins such as HSP60 in the defense against reactive oxygen species.

PMID- 24582288
TI  - Diffusion kurtosis imaging of the human kidney: a feasibility study.
AB  - PURPOSE: To assess the feasibility and to optimize imaging parameters of
      diffusion kurtosis imaging (DKI) in human kidneys. METHODS: The kidneys of ten
      healthy volunteers were examined on a clinical 3T MR scanner. For DKI,
      respiratory triggered EPI sequences were acquired in the coronal plane (3 b
      values: 0, 300, 600s/mm(2), 30 diffusion directions). A goodness of fit analysis
      was performed and the influence of the signal-to-noise ratio (SNR) on the DKI
      results was evaluated. Region-of-interest (ROI) measurements were performed to
      determine apparent diffusion coefficient (ADC), fractional anisotropy (FA) and
      mean kurtosis (MK) of the cortex and the medulla of the kidneys. Intra-observer
      and inter-observer reproducibility using Bland-Altman plots as well as subjective
      image quality of DKI were examined and ADC, FA, and MK parameters were compared.
      RESULTS: The DKI model fitted better to the experimental data (r=0.99) with
      p<0.05 than the common mono-exponential ADC model (r=0.96). Calculation of
      reliable kurtosis parameters in human kidneys requires a minimum SNR of 8.31 on
      b=0s/mm(2) images. Corticomedullary differentiation was possible on FA and MK
      maps. ADC, FA and MK revealed significant differences in medulla (ADC=2.82 * 10(
      3)mm(2)/s+/-0.25, FA=0.42+/-0. 05, MK=0.78+/-0.07) and cortex (ADC=3.60 * 10(
      3)mm(2)/s+/-0.28, FA=0.18+/-0.04, MK=0.94+/-0.07) with p<0.001. CONCLUSION: Our
      initial results indicate the feasibility of DKI in the human kidney presuming an
      adequate SNR. Future studies in patients with kidney diseases are required to
      determine the value of DKI for functional kidney imaging.

PMID- 24582289
TI  - Indications and technical challenges of total hip arthroplasty in the elderly
      after acetabular fracture.
AB  - INTRODUCTION: With people living longer and healthier lives, acetabular fractures
      in the elderly are becoming more common. But these fractures are still much less
      common than proximal femur fractures. Because of an insufficient number of cases,
      prospective studies with good statistical power have not yet been performed.
      Nevertheless, a collective, multicentre analysis of these injuries and their
      prognosis would help to define clinical practice recommendations. MATERIAL AND
      METHODS: As with younger subjects, the initial assessment for acetabular
      fractures in the elderly must be comprehensive and include detailed radiological
      evaluation and precise analysis of the fracture. Accurate diagnosis of the
      fracture type and displacement will allow the surgeon to follow a decision tree,
      with options ranging from functional treatment to emergency total hip
      arthroplasty (THA), depending on the patient's condition. CONCLUSION: THA
      treatment of these fractures is challenging for the surgeon in several aspects.
      These include determining the waiting time before the procedure, selecting the
      surgical approach, problems related to any existing hardware, need for bone
      grafting, primary fixation of the cup, dislocation risks, and the patient's
      ability to recover from an extensive and often complex surgery. LEVEL OF PROOF:
      Level V: expert opinion.

PMID- 24582290
TI  - Biomechanical evaluation of a new design titanium miniplate for the treatment of
      mandibular angle fractures.
AB  - The optimal management of mandibular angle fractures remains controversial. The
      aim of this experimental study was to test the stability and resistance to
      mechanical force of a new titanium miniplate design. Thirty fresh sheep
      hemimandibles, sectioned at the angle region, were used to evaluate two plating
      techniques. One group received fixation via a new design single non-compression
      titanium miniplate and the second group via a six-hole straight non-compression
      titanium miniplate. A custom-made biomechanical test model was used for the
      samples. Each hemimandible was subjected to compressive and tensile forces using
      an Instron machine. The biomechanical forces (N) that caused 4-mm displacement or
      fixation loosening were compared. Comparison between the groups showed that
      fixation with the new design miniplate had more resistance to lateral compression
      forces than with a six-hole straight miniplate (P<0.009). Moreover, the new
      design miniplate fixation displayed more resistance to vertical compression and
      tensile forces (P>0.46 and P>0.61, respectively). The study demonstrated that
      mandibular fracture fixation with the new design non-compression titanium
      miniplate offered greater resistance to lateral displacement forces and may also
      provide increased resistance to vertical compressive and tensile forces than a
      conventional six-hole straight miniplate. 

PMID- 24582291
TI  - Evaluation of diabetic foot screening in Primary Care.
AB  - AIM: To ascertain whether patients with type 2 diabetes are screened for diabetic
      foot, and to analyze the factors related to patients and centers associated to
      performance of such screening. MATERIAL AND METHODS: A multicenter,
      epidemiological, cross-sectional study was conducted. The clinical records of 443
      patients with type 2 diabetes monitored at Primary Care for at least 12 months
      were reviewed. Demographic and healthcare variables and characteristics of the
      primary care center were recorded. RESULTS: In the previous year, 51.2% of
      patients had been trained on foot self-care, 56.4% had undergone foot inspection,
      39.5% had been examined with a monofilament, and palpation of peripheral pulses
      and measurement of the ankle-brachial index were performed in 45.8 and 10.1% of
      patients, respectively. Diabetic foot screening (inspection, monofilament
      testing, and palpation of peripheral pulses) was performed in 37% of study
      patients. Ulcer risk stratification was done in 12.4% of patients. A significant
      association was found between diabetic foot screening and presence of foot
      deformities (P<.001), history of neuropathy (P=.005), and history of peripheral
      artery disease (P<.05). Screening was also associated to some characteristics of
      the center, such as reception of information about goal achievement (P<.001) and
      economic incentives for goal attainment (P<.001). CONCLUSIONS: Compliance with
      diabetic foot screening and ulcer risk stratification in patients with type 2
      diabetes in Primary Care was poor.

PMID- 24582293
TI  - Celebration meets caution: LARC's boons, potential busts, and the benefits of a
      reproductive justice approach.

PMID- 24582294
TI  - [An original oncoplastic reduction mammaplasty technique for breast cancers with
      high risk of incomplete excision].
AB  - Oncoplastic reduction mammaplasty (ORM), like breast-conserving treatments for
      cancer, has a risk of incomplete excision, and sometimes requires complementary
      mastectomy. In that case difficulties may occur due to skin shortness induced by
      recent surgery. Review of bibliography brings evidence that some factors are
      predictive of incomplete excision. When a patient has one or more of these
      factors, surgeon should anticipate complementary mastectomy. Horizontal ORM
      should be reminded for they allow secondary mastectomy in a horizontal way to be
      performed. An adaptation of the inverted T pattern is proposed, also permitting
      mastectomy in a horizontal way. These solutions allow neither to alter skin
      healing nor to compromise the future breast reconstruction. 

PMID- 24582292
TI  - A pilot study of depot medroxyprogesterone acetate pharmacokinetics and weight
      gain in adolescent females.
AB  - OBJECTIVE: To explore the relationship between medroxyprogesterone acetate (MPA)
      pharmacokinetic (PK) parameter estimates and weight gain. STUDY DESIGN:
      Prospective study of adolescents (N=40; age 12-21 years) initiating DMPA. PK
      parameters were calculated: maximum MPA concentration (Cmax, ng/mL), time to Cmax
      (Tmax, days) and elimination rate constant (ng/mL/day). Optimal PK cut points
      were determined for predicting body mass index (BMI) increase >=10%. RESULTS:
      Cmax <2.88 ng/mL and elimination rate constant <0.021 ng/mL/day were associated
      (p<.05) with BMI increase >=10%. Elimination rate constant was most predictive of
      weight gain. CONCLUSIONS: PK evaluation may help identify adolescents at risk of
      excessive DMPA-associated weight gain.

PMID- 24582295
TI  - [Cardiovascular risks of combined oral contraceptives - beyond the French
      controversy].
AB  - Combined hormonal contraceptive is the most used contraceptive method in France
      among childbearing-aged women. Following the temporary delisting of oral
      contraception containing a 3rd generation progestin and following the market
      withdrawal of oral pills containing cyproterone acetate in combination with
      ethynil-estradiol (35MUg), the impact of these events on our prescribing practice
      remains to determine. We will especially discuss the cardiovascular risk
      associated with combined hormonal contraceptives in the light of the most recent
      publications either with epidemiological or biological data. 

PMID- 24582296
TI  - Introduction to the Festschrift for Robert C. Waag.

PMID- 24582297
TI  - Physical models of tissue in shear fields.
AB  - This review considers three general classes of physical as opposed to
      phenomenological models of the shear elasticity of tissues. The first is simple
      viscoelasticity. This model has a special role in elastography because it is the
      language in which experimental and clinical data are communicated. The second
      class of models involves acoustic relaxation, in which the medium contains inner
      time-dependent systems that are driven through the external bulk medium.
      Hysteresis, the phenomenon characterizing the third class of models, involves
      losses that are related to strain rather than time rate of change of strain. In
      contrast to the vast efforts given to tissue characterization through their bulk
      moduli over the last half-century, similar research using low-frequency shear
      data is in its infancy. Rather than a neat summary of existing facts, this essay
      is a framework for hypothesis generation-guessing what physical mechanisms give
      tissues their shear properties. 

PMID- 24582298
TI  - The delayed onset of subharmonic and ultraharmonic emissions from a phospholipid
      shelled microbubble contrast agent.
AB  - Characterizing the non-linear response of microbubble contrast agents is
      important for their efficacious use in imaging and therapy. In this article, we
      report that the subharmonic and ultraharmonic response of lipid-shelled
      microbubble contrast agents exhibits a strong temporal dependence. We
      characterized non-linear emissions from Targestar-p microbubbles (Targeson Inc.,
      San Diego, CA, USA) periodically for 60 min, at 10 MHz excitation frequency. The
      results revealed a considerable increase in the subharmonic and ultraharmonic
      response (nearly 12-15 and 5-8 dB) after 5-10 min of agent preparation. However,
      the fundamental and the harmonic response remained almost unchanged in this
      period. During the next 50 min, the subharmonic, fundamental, ultraharmonic, and
      harmonic responses decreased steadily by 2-5 dB. The temporal changes in the non
      linear behavior of the agent appeared to be primarily mediated by gas-exchange
      through the microbubble shell; temperature and prior acoustic excitation based
      mechanisms were ruled out. Further, there was no measurable change in the agent
      size distribution by static diffusion. We envisage that these findings will help
      obtain reproducible measurements from agent characterization, non-linear imaging,
      and fluid-pressure sensing. These findings also suggest the possibility for
      improving non-linear imaging by careful design of ultrasound contrast agents.

PMID- 24582299
TI  - A novel high level canonical piecewise linear model based on the simplicial
      partition and its application.
AB  - The piecewise linear (PWL) model has attracted more and more attention in recent
      research because it can handle complex nonlinearity while maintaining linearity
      in local regions. A large number of compact representations for PWL modeling have
      been introduced, such as hinging hyperplanes and its generalized version.
      However, the existing methods usually give rise to many and complex subregions,
      which is an issue known as "curse of partitions", and hampered practical
      applications of PWL models. In this paper, a novel high level canonical PWL model
      is presented to tackle the curse of partitions. In more detail, an improved
      simplicial partition strategy with alterable intervals is proposed to improve the
      model representation capability. The proposed PWL model guarantees an
      unchangeable topology during training and thus a limited number of subregions
      after training. Several numerical experiments, and a simulated chemical process,
      are used to demonstrate the effectiveness of the proposed model. 

PMID- 24582300
TI  - An improved spectral analysis of the stray flux component for the detection of
      air-gap irregularities in squirrel cage motors.
AB  - For machines' monitoring purpose, the classical motor current signature analysis
      has shown its weakness in distinguishing the eccentricity occurrence in presence
      of others mechanical faults. Although Park's vector approach can cover this
      drawback, the high cost due to the requirement to use three current sensors
      associated with an advanced processing technique, makes it less desired by
      industrialists. In this paper, we suggest an alternative diagnosis method based
      on a suitable processing of the stray flux data. The experimental results have
      revealed the potential of a simple search coil for the detection and the
      distinction of the accurate eccentricity nature even in presence of similar
      mechanical faults. 

PMID- 24582301
TI  - Tolerogenic microenvironment in neonatal period induced by maternal immunization
      with ovalbumin.
AB  - Maternal immunization with allergens, such as ovalbumin (OVA), can inhibit the
      development of an allergic response in offspring. The regulatory mechanisms seem
      to be mediated by maternal antibodies (MatAbs) and factors generated by the
      maternal-fetal interface. The aim of this study was to verify the pathways of
      inhibitory Ab transference after maternal immunization with OVA and the effect of
      the offspring's dendritic cells (DCs) on the generation of regulatory T (Treg)
      cells. We verified that preconceptional OVA immunization induces high levels of
      proinflammatory and regulatory cytokines in the amniotic fluid, allowing the
      transference of high levels of anti-OVA IgG1 Abs to the offspring. Using an
      adoptive nursing protocol, we verified that maternal immunization leads to MatAb
      transference by the placental route and by breastfeeding contribute to the
      inhibition of anaphylactic IgE and IgG1 Ab responses in immunized offspring. We
      observed that maternal immunization decreased eosinophil numbers in recovered
      bronchoalveolar lavage fluid and in the lung tissue, whereas with a lack of
      control of airway responsiveness to methacholine. Maternal immunization induced
      in young offspring a decreased percentage of CD11c+ DCs expressing MHC class II
      and CD40 molecules. Moreover, DCs from both groups of offspring when pulsed with
      OVA, were able to induce Treg cells in vitro. Similarly, OVA immunization at the
      neonatal stage increased the frequency of Treg cells, regardless of the mother's
      immunization status. These findings emphasize that maternal immunization leads to
      a complex interaction of regulatory factors, with MatAbs, DCs and Treg cells
      affecting the tolerance of offspring during an allergic response. 

PMID- 24582302
TI  - The trauma report nurse: a trauma triage process improvement project.
AB  - INTRODUCTION: Accurate trauma triage is imperative to facilitate appropriate
      resource mobilization for severely injured trauma patients. A critical window of
      opportunity exists to prevent secondary injury or death. Timely assessment with a
      multidisciplinary trauma team is essential to facilitate rapid diagnosis and
      treatment. However, consistent and accurate trauma triage proved daunting at our
      institution, resulting in instances of undertriage. METHODS: A process
      improvement strategy aimed at improving trauma triage accuracy was implemented.
      An innovative role, the trauma report nurse (TRN), was created and became the
      trauma nurse expert. The TRN was responsible for assigning a trauma triage level
      to all incoming adult and pediatric trauma patients. In parallel, improvements
      were made to the prehospital report format, increasing standardization and
      clarifying hand-off verbiage. RESULTS: Undertriage rates dropped from 14% to
      4.8%. Qualitative data demonstrated acceptance and support of the TRN role among
      physicians, nurses and nursing and ancillary staff. DISCUSSION: Designating
      trauma triage to an ED registered nurse proved to reduce undertriage rates. By
      providing staff education, infrastructure improvements, and leadership support,
      the role continues to thrive, resulting in improved care for severely injured
      trauma patients.

PMID- 24582304
TI  - Rural aquaculture as a sustainable alternative for forest conservation in the
      Monarch Butterfly Biosphere Reserve, Mexico.
AB  - Forest conservation plays a significant role in environmental sustainability. In
      Mexico only 8.48 million ha of forest are used for conservation of biodiversity.
      Payment for Environmental Services in the Monarch Butterfly Biosphere Reserve,
      one of the most important national protected areas, contributes to the
      conservation of these forests. In the Reserve, production of rainbow trout has
      been important for the rural communities who need to conserve the forest cover in
      order to maintain the hibernation cycle of the butterfly. Aquaculture is a highly
      productive activity for these protected areas, since it harnesses the existing
      water resources. In this study, changes from 1999 to 2012 in vegetation and land
      use cover in the El Lindero basin within the Reserve were evaluated in order to
      determine the conservation status and to consider the feasibility of aquaculture
      as a means of sustainable development at community level. Evaluation involved
      stereoscopic interpretation of digital aerial photographs from 1999 to 2012 at
      1:10,000 scale, comparative analysis by orthocorrected mosaics and restitution on
      the mosaics. Between 1999 and 2012, forested land recovered by 28.57 ha (2.70%)
      at the expense of non-forested areas, although forest degradation was 3.59%.
      Forest density increased by 16.87%. In the 46 ha outside the Reserve,
      deforestation spread by 0.26%, and land use change was 0.11%. The trend towards
      change in forest cover is closely related to conservation programmes,
      particularly payment for not extracting timber, reforestation campaigns and
      surveillance, whose effects have been exploited for the development of rural
      aquaculture; this is a new way to improve the socio-economic status of the
      population, to avoid logging and to achieve environmental sustainability in the
      Reserve.

PMID- 24582303
TI  - Patterns of care and survival of glioblastoma patients: a comparative study
      between 2004 and 2008 in Lyon, France.
AB  - INTRODUCTION: The treatment of glioblastomas (GBMs) has changed significantly
      since 2005. However, the extent to which this change has improved overall
      survival (OS) of patients treated outside clinical trials remains to be
      determined. METHODS: We compared the patterns of care and OS of all GBM patients
      diagnosed in 2004 (n=105) and in 2008 (n=130) in our center. RESULTS: Younger
      patients (aged<70 years) diagnosed in 2008 received temozolomide
      radiochemotherapy as the initial treatment and bevacizumab at recurrence more
      frequently than those diagnosed in 2004 (69% vs 26% P<10(-4) and 41% vs 3%, P<10(
      4), respectively). Elderly patients (aged>=70 years) diagnosed in 2008 received
      an oncological treatment (radiotherapy and/or chemotherapy) more frequently than
      those diagnosed in 2004 (67% vs 38%, P=0.006). The patients diagnosed in 2008 had
      longer OS than those diagnosed in 2004 (10.5 months vs 5.3 months, P=0.001). This
      finding was true for both younger and elderly patients (15.3 months vs 8.9
      months, P=0.02 and 6.4 months vs 3.2 months, P=0.0002, respectively) and when
      considering only IDH1 wild-type patients (8.9 months vs 5.3 months, P=0.004).
      CONCLUSION: In our center, the change in the patterns of care for GBMs between
      2004 and 2008 has been associated with a significant improvement in OS.

PMID- 24582305
TI  - Ultrasonic extraction of steroidal alkaloids from potato peel waste.
AB  - Potato processors produce large volumes of waste in the form of potato peel which
      is either discarded or sold at a low price. Potato peel waste is a potential
      source of steroidal alkaloids which are biologically active secondary metabolites
      which could serve as precursors to agents with apoptotic, chemopreventive and
      anti-inflammatory properties. The present study investigated the relative
      efficacy of ultrasound assisted extraction (UAE) and solid liquid extraction
      (SLE) both using methanol, to extract steroidal alkaloids from potato peel waste
      and identified optimal conditions for UAE of alpha-solanine, alpha-chaconine,
      solanidine and demissidine. Using response surface methodology optimal UAE
      conditions were identified as an amplitude of 61 MUm and an extraction time of 17
      min which resulted the recovery of 1102 MUg steroidal alkaloids/g dried potato
      peel (DPP). In contrast, SLE yielded 710.51 glycoalkaloid MUg/g DPP. Recoveries
      of individual glycoalkoids using UAE yielded 273, 542.7, 231 and 55.3 MUg/g DPP
      for alpha-solanine, alpha-chaconine, solanidine and demissidine respectively.
      Whereas for SLE yields were 180.3, 337.6, 160.2 and 32.4 MUg/g DPP for alpha
      solanine, alpha-chaconine, solanidine and demissidine respectively. The predicted
      values from the developed second order quadratic polynomial equation were in
      close agreement with the experimental values with low average mean deviation
      (E<5%) values. Predicted models were highly significant (p<0.05) for all
      parameters studied. This study indicates that UAE has strong potential as an
      extraction method for steroidal alkaloids from potato peel waste.

PMID- 24582306
TI  - [Cementless total hip arthroplasty after acute femoral neck fracture in active
      patients. Prospective matched study with a minimum follow-up of 5 years].
AB  - OBJECTIVES: To evaluate outcomes of cementless total hip replacement after acute
      femoral neck fracture in active patients. MATERIAL AND METHODS: A prospective
      matched study was conducted to compare the results between 76 patients with
      fractures and 76 patients with osteoarthritis. The Harris score, short-WOMAC and
      SF-12 were used for the clinical assessment. The mean follow-up was 7.3 years
      (range 5-11). RESULTS: There were no significant differences in medical or
      surgical complications between the 2 groups. Functional outcomes were similar,
      but more walking aids were used in fracture group. There were 6 revisions among
      the fractures group (one dislocation, 2 deep infections, 3 aseptic loosening),
      and 2 aseptic loosening among controls. There was no significant difference in
      arthroplasty survival at 10 years (88.7 vs. 96.1%, P=.15). The mortality rates at
      2 and 10 years were similar. CONCLUSION: Cementless total hip replacement for
      treatment of acute femoral neck fracture showed similar results to those of
      elective surgery for osteoarthritis in these selected patients.

PMID- 24582307
TI  - Patients with drug-refractory atrioventricular nodal reentrant tachycardia:
      clinical features, electrophysiological characteristics, and predictors of
      medication failure.
AB  - BACKGROUND AND PURPOSE: Drug responses vary markedly from patient to patient in
      atrioventricular nodal reentrant tachycardia (AVNRT), the most common form of
      paroxysmal regular supraventricular tachycardia in adults. However, clinical and
      electrophysiological (EP) characteristics of patients with AVNRT whose
      tachycardia attacks could not be adequately controlled by antiarrhythmic agents
      have not been studied in a large patient cohort. We aimed to define the clinical
      and EP features of patients with drug-refractory AVNRT. METHODS AND RESULTS: A
      total of 266 consecutive patients with AVNRT undergoing catheter ablation after a
      period of medical treatment were analyzed: 144 patients with drug-refractory
      AVNRT (Group 1) and 122 patients with drug-responsive AVNRT (Group 2). Age was
      significantly higher (p=0.027) and the presence of hypertension (p=0.030),
      diabetes mellitus (p=0.047), and valvular heart diseases (p=0.008) was more
      frequent in Group 1 compared to Group 2. Among the EP features, atrial-His jump
      (81% vs 69%, p=0.028) and atrial vulnerability (26% vs 14%, p=0.018) were
      significantly higher, echo zone was significantly more long-lasting (44 +/- 24 ms
      vs 38 +/- 22 ms, p=0.018), and tachycardia cycle length (TCL) was significantly
      longer (348 +/- 41 ms vs 329 +/- 38 ms, p=0.000) in Group 1 than in Group 2.
      Multivariate analysis showed that hypertension (p=0.036), valvular heart disease
      (p=0.014), atrial vulnerability (p=0.037), TCL (p=0.003), and wide echo zone
      (p=0.028) were independent predictors for drug-refractory AVNRT. CONCLUSION: In
      the presence of hypertension, valvular heart disease, atrial vulnerability, long
      lasting echo zone, and relatively slow AVNRT, medical treatment is less likely to
      prevent the tachycardia episodes.

PMID- 24582308
TI  - Novel dyssynchrony evaluation by M-mode imaging in left bundle branch block and
      the application to predict responses for cardiac resynchronization therapy.
AB  - BACKGROUND: To determine an appropriate M-mode method in assessing left
      ventricular (LV) dyssynchrony in left bundle branch block (LBBB), and to assess
      feasibility of the method to predict cardiac resynchronization therapy (CRT)
      responses. METHODS AND RESULTS: Fifty-one patients with LBBB were enrolled. Among
      them 31 patients underwent CRT. In addition to original septal to posterior wall
      motion delay (SPWMD), first peak-SPWMD was proposed as time of difference between
      the first septal displacement and the maximum displacement of the posterior. If
      an early septal point was not present, anatomical M-mode was used to visualize an
      early septal displacement spreading scan-area until inferoseptal wall. CRT
      responders were defined as LV end-systolic volume reduction (>15%) at 6 months
      after CRT. Twenty patients (65%) were identified as CRT responders. First peak
      SPWMD in responders was significantly higher than those in nonresponders,
      although SPWMD did not differ between groups. Strong predicting ability of first
      peak-SPWMD was revealed (first peak-SPWMD: 80/90/83%; SPWMD: 35/100/58%), and
      area under the curve in receiver operating characteristic analysis of first peak
      SPWMD (0.88) was significantly higher than that of SPWMD (0.61) (p<0.05).
      CONCLUSION: In patients with LBBB, time differences between early septal and
      delayed displacement of posterolateral wall on M-mode images were the appropriate
      dyssynchrony parameter, and could improve the predictive ability for CRT
      responses.

PMID- 24582309
TI  - Mastocytosis associated with a rare germline KIT K509I mutation displays a well
      differentiated mast cell phenotype.
AB  - BACKGROUND: Mastocytosis associated with germline KIT activating mutations is
      exceedingly rare. We report the unique clinicopathologic features of a patient
      with systemic mastocytosis caused by a de novo germline KIT K509I mutation.
      OBJECTIVES: We sought to investigate the effect of the germline KIT K509I
      mutation on human mast cell development and function. METHODS: Primary human mast
      cells derived from CD34(+) peripheral blood progenitors were examined for growth,
      development, survival, and IgE-mediated activation. In addition, a mast cell
      transduction system that stably expressed the KIT K509I mutation was established.
      RESULTS: KIT K509I biopsied mast cells were round, CD25(-), and well
      differentiated. KIT K509I progenitors cultured in stem cell factor (SCF)
      demonstrated a 10-fold expansion compared with progenitors from healthy subjects
      and developed into mature hypergranular mast cells with enhanced antigen-mediated
      degranulation. KIT K509I progenitors cultured in the absence of SCF survived but
      lacked expansion and developed into hypogranular mast cells. A KIT K509I mast
      cell transduction system revealed SCF-independent survival to be reliant on the
      preferential splicing of KIT at the adjacent exonic junction. CONCLUSION:
      Germline KIT mutations associated with mastocytosis drive a well-differentiated
      mast cell phenotype distinct to that of somatic KIT D816V disease, the oncogenic
      potential of which might be influenced by SCF and selective KIT splicing.

PMID- 24582310
TI  - Mitochondrial STAT3 plays a major role in IgE-antigen-mediated mast cell
      exocytosis.
AB  - BACKGROUND: The involvement of mitochondrial oxidative phosphorylation (OXPHOS)
      in mast cell exocytosis was recently suggested by the finding that mitochondria
      translocate to exocytosis sites upon mast cell activation. In parallel,
      mitochondrial signal transducer and activator of transcription 3 (STAT3) was
      found to be involved in ATP production. However, the regulation of mitochondrial
      STAT3 function and its connection to mast cell exocytosis is unknown. OBJECTIVE:
      We sought to explore the role played by mitochondrial STAT3 in mast cell
      exocytosis. METHODS: Experiments were performed in vitro with human and mouse
      mast cells and rat basophilic leukemia (RBL) cells and in vivo in mice. OXPHOS
      activity was measured after immunologic activation. The expression of STAT3,
      extracellular signal-regulated kinase 1/2, and protein inhibitor of activated
      STAT3 in the mitochondria during mast cell activation was determined, as was the
      effect of STAT3 inhibition on OXPHOS activity and mast cell function. RESULTS:
      Here we show that mitochondrial STAT3 is essential for immunologically mediated
      degranulation of human and mouse mast cells and RBL cells. Additionally, in IgE
      antigen-activated RBL cells, mitochondrial STAT3 was phosphorylated on serine 727
      in an extracellular signal-regulated kinase 1/2-dependent manner, which was
      followed by induction of OXPHOS activity. Furthermore, the endogenous inhibitor
      of STAT3, protein inhibitor of activated STAT3, was found to inhibit OXPHOS
      activity in the mitochondria, resulting in inhibition of mast cell degranulation.
      Moreover, mice injected with Stattic, a STAT3 inhibitor, had a significant
      decrease in histamine secretion. CONCLUSION: These results provide the first
      evidence of a regulatory role for mitochondrial STAT3 in mast cell functions, and
      therefore mitochondrial STAT3 could serve as a new target for the manipulation of
      allergic diseases.

PMID- 24582311
TI  - Recommendations for live viral and bacterial vaccines in immunodeficient patients
      and their close contacts.
AB  - The present uncertainty of which live viral or bacterial vaccines can be given to
      immunodeficient patients and the growing neglect of societal adherence to routine
      immunizations has prompted the Medical Advisory Committee of the Immune
      Deficiency Foundation to issue recommendations based on published literature and
      the collective experience of the committee members. These recommendations address
      the concern for immunodeficient patients acquiring infections from healthy
      subjects who have not been immunized or who are shedding live vaccine-derived
      viral or bacterial organisms. Such transmission of infectious agents can occur
      within the hospital, clinic, or home or at any public gathering. Collectively, we
      define this type of transmission as close-contact spread of infectious disease
      that is particularly relevant in patients with impaired immunity who might have
      an infection when exposed to subjects carrying vaccine-preventable infectious
      diseases or who have recently received a live vaccine. Immunodeficient patients
      who have received therapeutic hematopoietic stem transplantation are also at risk
      during the time when immune reconstitution is incomplete or while they are
      receiving immunosuppressive agents to prevent or treat graft-versus-host disease.
      This review recommends the general education of what is known about vaccine
      preventable or vaccine-derived diseases being spread to immunodeficient patients
      at risk for close-contact spread of infection and describes the relative risks
      for a child with severe immunodeficiency. The review also recommends a balance
      between the need to protect vulnerable subjects and their social needs to
      integrate into society, attend school, and benefit from peer education. 

PMID- 24582313
TI  - Allergen challenge in allergic rhinitis rapidly induces increased peripheral
      blood type 2 innate lymphoid cells that express CD84.

PMID- 24582314
TI  - Sputum gene expression signature of 6 biomarkers discriminates asthma
      inflammatory phenotypes.
AB  - BACKGROUND: Airway inflammation is associated with asthma exacerbation risk,
      treatment response, and disease mechanisms. OBJECTIVE: This study aimed to
      identify and validate a sputum gene expression signature that discriminates
      asthma inflammatory phenotypes. METHODS: An asthma phenotype biomarker discovery
      study generated gene expression profiles from induced sputum of 47 asthmatic
      patients. A clinical validation study (n = 59 asthmatic patients) confirmed
      differential expression of key genes. A 6-gene signature was identified and
      evaluated for reproducibility (n = 30 asthmatic patients and n = 20 control
      subjects) and prediction of inhaled corticosteroid (ICS) response (n = 71
      asthmatic patients). Receiver operating characteristic curves were calculated,
      and area under the curve (AUC) values were reported. RESULTS: From 277
      differentially expressed genes between asthma inflammatory phenotypes, we
      identified 23 genes that showed highly significant differential expression in
      both the discovery and validation populations. A signature of 6 genes, including
      Charcot-Leydon crystal protein (CLC); carboxypeptidase A3 (CPA3);
      deoxyribonuclease I-like 3 (DNASE1L3); IL-1beta (IL1B); alkaline phosphatase,
      tissue-nonspecific isozyme (ALPL); and chemokine (C-X-C motif) receptor 2
      (CXCR2), was reproducible and could significantly (P < .0001) discriminate
      eosinophilic asthma from other phenotypes, including patients with
      noneosinophilic asthma (AUC, 89.6%), paucigranulocytic asthma (AUC, 92.6%), or
      neutrophilic asthma (AUC, 91.4%) and healthy control subjects (AUC, 97.6%), as
      well as discriminating patients with neutrophilic asthma from those with
      paucigranulocytic asthma (AUC, 85.7%) and healthy control subjects (AUC, 90.8).
      The 6-gene signature predicted ICS response (>12% change in FEV1; AUC, 91.5%).
      ICS treatment reduced the expression of CLC, CPA3, and DNASE1L3 in patients with
      eosinophilic asthma. CONCLUSIONS: A sputum gene expression signature of 6
      biomarkers reproducibly and significantly discriminates inflammatory phenotypes
      of asthma and predicts ICS treatment response. This signature has the potential
      to become a useful diagnostic tool to assist in the clinical diagnosis and
      management of asthma.

PMID- 24582315
TI  - The BLNK adaptor protein has a nonredundant role in human B-cell differentiation.
AB  - BACKGROUND: Expression of the pre-B-cell receptor (pre-BCR) by pre-BII cells
      constitutes a crucial checkpoint in B-cell differentiation. Mutations that affect
      the pre-B-cell receptor result in early B-cell differentiation blockades that
      lead to primary B-cell immunodeficiencies. BLNK adaptor protein has a key role in
      the pre-B-cell receptor signaling cascade, as illustrated by the abnormal B-cell
      development in the 4 patients with BLNK gene defects reported to date. However,
      the BLNK protein's precise function in human B-cell differentiation has not been
      completely specified. METHODS: B-cell development, including IgVH and Vk chain
      repertoires analysis, was studied in the bone marrow of a new case of BLNK
      deficiency in vitro and in vivo. RESULTS: Here, we report on a patient with
      agammaglobulinemia, with a total absence of circulating B cells. We detected a
      homozygous mutation in BLNK, which leads to the complete abrogation of BLNK
      protein expression. In the bone marrow, we identified a severe differentiation
      blockade at the pre-BI- to pre-BII-cell transition. IgVH gene rearrangements and
      selection of the IgH repertoire were normal, whereas the patient's pre-BI cells
      showed very restricted usage of the IgVkappa repertoire. Complementation of bone
      marrow progenitors from the patient with the BLNK gene and transplantation into
      NOD/SCID/gammacko mice allowed the complete restoration of B-cell differentiation
      and a normal usage of the IgVkappa genes.

PMID- 24582316
TI  - Efficacy and safety of an anti-IL-13 mAb in patients with severe asthma: a
      randomized trial.
AB  - BACKGROUND: Approximately 5% to 10% of asthmatic patients achieve incomplete
      symptom control on current therapies. The association of IL-13 with asthma
      pathology and reduced corticosteroid sensitivity suggests a potential benefit of
      anti-IL-13 therapy in refractory asthma. GSK679586, a humanized mAb, inhibits IL
      13 binding to both IL-13 receptor alpha1 and alpha2. OBJECTIVES: We sought to
      evaluate the efficacy and safety of GSK679586 in patients with severe asthma
      refractory to maximally indicated doses of inhaled corticosteroids. METHODS:
      Patients who remained symptomatic (Asthma Control Questionnaire score >=1.5)
      after uptitration to 1000 MUg/d fluticasone propionate or greater were randomized
      to 3 once-monthly intravenous infusions of 10 mg/kg GSK679586 (n = 99) or placebo
      (n = 99). RESULTS: Treatment differences in adjusted mean change from baseline
      over 12 weeks were nonsignificant for Asthma Control Questionnaire symptom scores
      (the primary end point; GSK679586 = -0.31, placebo = -0.17, P = .058) and FEV1
      (GSK679586 = -0.01, placebo = 0.03, P = .276). Similar analyses in patients with
      increased serum IgE levels, blood eosinophil counts, or both were also negative.
      Incidence of asthma exacerbations was similar between treatments. Most adverse
      events were nonserious and unrelated to treatment. Two GSK679586-treated patients
      had treatment-related serious adverse events (lethargy and supraventricular
      extrasystoles). CONCLUSIONS: Although well tolerated, GSK679586 did not
      demonstrate clinically meaningful improvements in asthma control, pulmonary
      function, or exacerbations in patients with severe asthma. Further studies are
      needed to determine whether therapies targeting IL-13, the functionally related
      IL-4 cytokine, or both can provide clinical benefit in patients with severe
      refractory asthma or a subpopulation of these patients beyond that achievable
      with high-dose corticosteroids.

PMID- 24582312
TI  - Clinical picture and treatment of 2212 patients with common variable
      immunodeficiency.
AB  - BACKGROUND: Common variable immunodeficiency (CVID) is an antibody deficiency
      with an equal sex distribution and a high variability in clinical presentation.
      The main features include respiratory tract infections and their associated
      complications, enteropathy, autoimmunity, and lymphoproliferative disorders.
      OBJECTIVE: This study analyzes the clinical presentation, association between
      clinical features, and differences and effects of immunoglobulin treatment in
      Europe. METHODS: Data on 2212 patients with CVID from 28 medical centers
      contributing to the European Society for Immunodeficiencies Database were
      analyzed retrospectively. RESULTS: Early disease onset (<10 years) was very
      frequent in our cohort (33.7%), especially in male subjects (39.8%). Male
      subjects with early-onset CVID were more prone to pneumonia and less prone to
      other complications suggesting a distinct disease entity. The diagnostic delay of
      CVID ranges between 4 and 5 years in many countries and is particularly high in
      subjects with early-onset CVID. Enteropathy, autoimmunity, granulomas, and
      splenomegaly formed a set of interrelated features, whereas bronchiectasis was
      not associated with any other clinical feature. Patient survival in this cohort
      was associated with age at onset and age at diagnosis only. There were different
      treatment strategies in Europe, with considerable differences in immunoglobulin
      dosing, ranging from 130 up to 750 mg/kg/mo. Patients with very low trough levels
      of less than 4 g/L had poor clinical outcomes, whereas higher trough levels were
      associated with a reduced frequency of serious bacterial infections. CONCLUSION:
      Patients with CVID are being managed differently throughout Europe, affecting
      various outcome measures. Clinically, CVID is a truly variable antibody
      deficiency syndrome.

PMID- 24582318
TI  - TLR9 expressed on plasma membrane acts as a negative regulator of human B cell
      response.
AB  - Toll-like receptors (TLRs) are positioned at the interface between innate and
      adaptive immunity. Unlike others, those such as TLR9, that recognize nucleic
      acids, are confined to the endosomal compartment and are scarce on the cell
      surface. Here, we present evidence for TLR9 expression on the plasma membrane of
      B cells. In contrast to endosomal TLR9, cell surface TLR9 does not bind CpG-B
      oligodeoxynucleotides. After B cell-receptor (BCR) stimulation, TLR9 was
      translocated into lipid rafts with the BCR, suggesting that it could serve as a
      co-receptor for BCR. Nevertheless, stimulation of B cells with anti-TLR9
      antibodies did not modify the BCR-induced responses despite up-regulation of
      tyrosine phosphorylation of proteins. However, CpG-B activation of B cells,
      acting synergistically with BCR signals, was inhibited by anti-TLR9 stimulation.
      Induction of CD25 expression and proliferation of B cells were thus down
      regulated by the engagement of cell surface TLR9. Overall, our results indicate
      that TLR9 expressed on the plasma membrane of B cells might be a negative
      regulator of endosomal TLR9, and could provide a novel control by which
      activation of autoreactive B cells is restrained. 

PMID- 24582319
TI  - Performance of the Directigen EZ Flu A+B rapid influenza diagnostic test to
      detect pandemic influenza A/H1N1 2009.
AB  - The Directigen EZ Flu A+B rapid influenza diagnostic test, as compared to real
      time reverse transcriptase polymerase chain reaction, demonstrated suboptimal
      performance to detect pandemic influenza A/H1N1 2009. Age- and viral load
      stratified test sensitivity ranged from 33.3 to 84.6% and 0 to 100%,
      respectively. 

PMID- 24582317
TI  - Beta-cell specific production of IL6 in conjunction with a mainly intracellular
      but not mainly surface viral protein causes diabetes.
AB  - Inflammatory mechanisms play a key role in the pathogenesis of type 1 and type 2
      diabetes. IL6, a pleiotropic cytokine with impact on immune and non-immune cell
      types, has been proposed to be involved in the events causing both forms of
      diabetes and to play a key role in experimental insulin-dependent diabetes
      development. The aim of this study was to investigate how beta-cell specific
      overexpression of IL-6 influences diabetes development. We developed two lines of
      rat insulin promoter (RIP)-lymphocytic choriomeningitis virus (LCMV) mice that
      also co-express IL6 in their beta-cells. Expression of the viral nucleoprotein
      (NP), which has a predominantly intracellular localization, together with IL6 led
      to hyperglycemia, which was associated with a loss of GLUT-2 expression in the
      pancreatic beta-cells and infiltration of CD11b(+) cells, but not T cells, in the
      pancreas. In contrast, overexpression of the LCMV glycoprotein (GP), which can
      localize to the surface, with IL-6 did not lead to spontaneous diabetes, but
      accelerated virus-induced diabetes by increasing autoantigen-specific CD8(+) T
      cell responses and reducing the regulatory T cell fraction, leading to increased
      pancreatic infiltration by CD4(+) and CD8(+) T cells as well as CD11b(+) and
      CD11c(+) cells. The production of IL-6 in beta-cells acts prodiabetic,
      underscoring the potential benefit of targeting IL6 in diabetes.

PMID- 24582320
TI  - Portal vein thrombosis and liver transplantation: implications for waiting list
      period, surgical approach, early and late follow-up.
AB  - Portal vein thrombosis (PVT) is a well-known and relatively common complication
      of liver cirrhosis. In the past, PVT was considered as a contraindication for
      liver transplantation (LT). To characterize prevalence, risk factors,
      perioperative management and outcome of PVT in the setting of LT, the English
      literature published between 1991 and 2011 was reviewed. Of 6807 articles, 280
      were selected, and 39 experiences were analyzed in detail (methodology, type and
      duration of treatments, peri-operative management, strategy to avoid recurrence,
      strengths and weaknesses, Oxford evidence level, citations). 3/39 studies were
      prospective; 9/39 were based on prospectively recorded databases; no studies of
      1, 2a, 3a level of evidence were present; 5/39 were recognized as level 2b, 23/39
      as level 3b, and 8/39 as level 4. High complication rate has been reported with
      consequent effect on graft and patient survival. Overall, PVT presents today good
      results similar to those obtained in patients without PVT undergoing LT even if
      they require a higher transfusion number and a longer ICU/hospital stay. Reported
      cases were retrospectively stratified according to Yerdel classification. Grade 1
      2 patients (76%) do well with eversion thromboendovenectomy, resection of damaged
      vein and porto-portal anastomosis. Results of patients with grade 3-4 (24%) are
      inferior, however data on outcome in this subsets are fragmented and do not allow
      a reliable analysis. Moreover, results obtained in grade 3-4 cases are better in
      transplant centers with large specific experience. The small number of reports
      suggests caution. The role of anticoagulant treatment is still debated. Although
      in cirrhotics with PVT LT remains a demanding procedure, PVT should not be
      considered a contraindication anymore. 

PMID- 24582321
TI  - The lifetime prevalence of child sexual abuse and sexual assault assessed in late
      adolescence.
AB  - PURPOSE: To estimate the likelihood that a recent cohort of children would be
      exposed to sexual abuse and sexual assault by age 17 in the United States.
      METHODS: This analysis draws on three very similarly designed national telephone
      surveys of youth in 2003, 2008, and 2011, resulting in a pooled sample of 708 17
      year-olds, 781 15-year-olds, and 804 16-year-olds. RESULTS: The lifetime
      experience of 17-year-olds with sexual abuse and sexual assault was 26.6% (95%
      confidence interval [CI] 19.8-33.5) for girls and 5.1% (95% CI 2.6-7.6) for boys.
      The lifetime experience with sexual abuse and sexual assault at the hands of
      adult perpetrators exclusively was 11.2% (95% CI 6.4-16.1) for females and 1.9%
      (95% CI .5-3.4) for males. For females, considerable risk for sexual abuse and
      assault was concentrated in late adolescence, as the rate rose from 16.8% (95% CI
      11.5-22.2) for 15-year-old females to 26.6% (95% CI 19.8-33.5) for 17-year-old
      females. For males, it rose from 4.3% (95% CI 1.9-6.8) at 15 years to 5.1% (2.6
      7.6) at 17 years. CONCLUSIONS: Self-report surveys in late adolescence reveal
      high rates of lifetime experience with sexual abuse and sexual assault at the
      hands of both adults and peers. Because of high continuing victimization during
      the late teen years, assessments are most complete when conducted among the
      oldest youth.

PMID- 24582323
TI  - Tegmen height: preoperative value of CT on preventing dural complications in
      chronic otitis media surgery.
AB  - OBJECTIVE: The objective was to examine tegmen height in patients with iatrogenic
      dural exposure in chronic otitis media (COM) surgery. METHODS: Computed
      tomographic (CT) scans of 50 patients who underwent COM surgery were
      retrospectively examined. Twelve patients with dural exposure were admitted to
      the dura group. The control group of 38 patients had no dural exposure. Tegmen
      heights in both groups were compared. RESULTS: There was no statistically
      significant difference between opposite ears (P>.05). Significant difference was
      found in tegmen height between healthy and operated ears in unilateral COM
      patients (P=.001). CONCLUSION: Preoperative CT assessment of tegmen height is an
      important parameter in assessing risk of exposing dura during surgery.

PMID- 24582322
TI  - Prevalence and risk factors for active convulsive epilepsy in rural northeast
      South Africa.
AB  - RATIONALE: Epilepsy is among the most common neurological disorders worldwide.
      However, there are few large, population-based studies of the prevalence and risk
      factors for epilepsy in southern Africa. METHODS: From August 2008 to February
      2009, as part of a multi-site study, we undertook a three-stage, population-based
      study, embedded within the Agincourt health and socio-demographic surveillance
      system, to estimate the prevalence and identify risk factors of active convulsive
      epilepsy (ACE) in a rural South African population. RESULTS: The crude prevalence
      of ACE, after adjusting for non-response and the sensitivity of the screening
      method, was 7.0/1,000 individuals (95% CI 6.4-7.6) with significant geographic
      heterogeneity across the study area. Being male (OR=2.3; 95% CI 1.6-3.2), family
      history of seizures (OR=4.0; 95% CI 2.0-8.1), a sibling with seizures (OR=7.0;
      95% CI 1.6-31.7), problems after delivery (OR=5.9; 95% CI 1.2-24.6), and history
      of snoring (OR=6.5; 95% CI 4.5-9.5) were significantly associated with ACE. For
      children, their mother's exposure to some formal schooling was protective
      (OR=0.30; 95% CI 0.11-0.84) after controlling for age and sex. Human
      immunodeficiency virus was not found to be associated with ACE. CONCLUSIONS: ACE
      is less frequent in this part of rural South Africa than other parts of sub
      Saharan Africa. Improving obstetric services could prevent epilepsy. The
      relationship between snoring and ACE requires further investigation, as does the
      relative contribution of genetic and environmental factors to examine the
      increased risk in those with a family history of epilepsy.

PMID- 24582324
TI  - Executive functions and memory in autogenous and reactive subtype of obsessive
      compulsive disorder patients.
AB  - There are concurrently with different results of studies about cognitive
      functions of Obsessive-Compulsive Disorder (OCD), impairment in non-verbal memory
      and executive functioning in OCD, has shown consistent results in several
      studies. In this study, 62 OCD patients and 40 healthy controls were
      participated. Firstly, cognitive functions of OCD group and healthy control group
      were compared in terms of scores in Stroop Test, Wisconsin Cart Sorting Test
      (WCST), Auditory Consonant Trigram Test (ACTT), Controlled Word Association Test
      (CWAT), Rey Auditory Verbal Learning Test (RAVLT), Digit Span Test (DST). And
      then, two patient groups of OCD patients (patients with autogenous obsessions and
      patients with reactive obsessions) were compared in terms of the scores of same
      tests, with a hypothesis that claims, cognitive functions of patients with
      autogenous obsessions, who shown schizotypal personality features and thought
      disorder in higher ratio, will show more impairment than cognitive functions of
      patients with reactive obsessions. Significant impairment was found in OCD
      patients in terms of Stroop test and WCST scores when compared to scores of
      healthy controls. There was no difference pointed out between cognitive functions
      of patients with autogenous obsessions and reactive obsessions. Due to limited
      number of patients with autogenous obsessions in current study, any future
      research with greater sample size will be helpful to explain the cognitive
      functions in OCD with autogenous and reactive obsessions. 

PMID- 24582325
TI  - Phenomenological subtypes of severe bipolar mixed states: a factor analytic
      study.
AB  - OBJECTIVE: The correct identification of bipolar mixed states (MS) has important
      implications for clinical practice. The aim of the study was to define the
      multidimensional psychopathological structure of severe MS. To our knowledge, no
      factor analytical studies including only patients with MS, have been conducted
      before. METHODS: In the first week of hospitalization, we evaluated by HAM-D-17,
      YMRS, BPRS and CGI, 202 Bipolar I inpatients with MS according to DSM-IV criteria
      referred for an ECT trial. A Principal-component analysis followed by Varimax
      rotation was performed on the 24-item BPRS. The relationships among different
      symptomatological subtypes and other clinical characteristics were explored.
      RESULTS: Six interpretable factors were extracted: Psychotic-positive symptoms,
      Mania, Disorientation-Unusual Motor Behaviour, Depression, Negative Symptoms and
      Anxiety. On the basis of the highest z-scores, we found 6 "dominant" BPRS factor
      groups, that were statistically distinct and without significant overlap in the
      main symptomatological presentation. Only 29 (14.4%) of our patients could be
      described as "Dominant Manic" and 48 (23.8%) as "Dominant Depressive"; most
      importantly 125 (61.9%) were neither predominately-manic nor predominately
      depressive. Variables including age, number of previous episodes, suicidal
      behavior and HAM-D and YMRS scores significantly differentiated the subtypes.
      CONCLUSION: At least in the most severe forms, MS appears to represent more than
      the superposition of affective symptoms of opposite polarity. Anxiety,
      perplexity, psychotic experiences, motor disturbances and grossly disorganized
      behavior seem to arise from protracted intra-episodic instability and presence of
      a drive state influencing the mood state and the emotional resonance.

PMID- 24582326
TI  - Could molecular effects of Caulerpa racemosa metabolites modulate the impact on
      fish populations of Diplodus sargus?
AB  - The green alga Caulerpa racemosa is a non-native, invasive species in the
      Mediterranean, and an important stressor for several native organisms. The algal
      capacity to produce secondary metabolites has been suggested to modulate success
      of the C. racemosa invasion, although many of potentially involved biological
      pathways still remain unexplored. In this respect, the aim of the present study
      was to investigate some molecular and cellular effects in the white seabream
      Diplodus sargus, an ecologically key species, which included the alien C.
      racemosa in its diet. Organisms were sampled in 2 seasonal periods from 3
      locations of Southern Italy, each characterized by different levels of algal
      abundance. The level of caulerpin, one of the main secondary algal metabolites,
      in fish tissues has been used as an indicator of the trophic exposure to the
      seaweed and related with molecular and cellular responses. Chemical analyses
      indicated that fish from invaded sites can accumulate caulerpin, with liver
      concentrations ranging from a few up to hundreds of MUg/g. Biomarkers analyses
      revealed only limited alterations of the main antioxidant defences, such as
      glutathione reductase and levels of glutathione; on the other hand, increased
      enzymatic activities of cytochrome P450, glutathione S-transferases and acyl CoA
      oxidase, as well as enhanced gene transcription for peroxisome proliferator
      activated receptor alpha, cytochrome P4501A and vitellogenin 1 were observed in
      fish more exposed to C. racemosa as indicated by liver concentrations of
      caulerpin higher than 50 MUg/g. Despite a direct molecular relationship with this
      algal metabolite could not be established, our results suggest that a C. racemosa
      enriched diet can modulate biotransformation and fatty acids metabolism of D.
      sargus. Assessing whether similar effects represent short- or long-term effects
      will be of crucial importance to understand consequences on the general health
      status and reproductive performance of exposed key fish species in the
      Mediterranean region. 

PMID- 24582328
TI  - Validity of measuring distal vastus medialis muscle using rehabilitative
      ultrasound imaging versus magnetic resonance imaging.
AB  - Objective quantification of muscle size can aid clinical assessment when treating
      musculoskeletal conditions. To date the gold standard of measuring muscle
      morphology is magnetic resonance imaging (MRI). However, there's a growing body
      of evidence validating rehabilitative ultrasound imaging (RUSI) against MRI.
      OBJECTIVE: This study aimed to validate RUSI against MRI for the linear
      measurements of the distal fibres of vastus medialis muscle in the thigh. Twelve
      healthy male participants were recruited from a local university population. The
      distal portion of their right vastus medialis was imaged with the participant in
      long-sitting, using MRI and RUSI whilst the leg was in extension and neutral hip
      rotation. Cross sectional area (CSA) and three linear measures were taken from
      the MRI and these were compared with the same linear measures from RUSI.
      Statistical analysis included comparison of MRI and RUSI measures using the
      paired t-test and intra-class correlation coefficients (ICC 3,1). Mean
      differences between the linear measures taken from the MRI and RUSI were -0.5 mm
      to 2.9 mm (95% confidence intervals -0.6-8.3 mm), which were not statistically
      different (p > 0.05) and were highly correlated (ICCs 3,1 0.84-0.94).
      Correlations between the three linear measurements and muscle CSA ranged from r =
      0.23 to 0.87, the greatest being muscle thickness. Multiplying the linear
      measures did not improve the correlation of 0.87 found for muscle thickness.
      Linear measures of vastus medialis depth made using RUSI were shown to be as
      valid as using MRI. Muscle thickness measures using RUSI could be used within an
      objective assessment of this muscle.

PMID- 24582327
TI  - Benchmarks for operative outcomes of robotic and open radical prostatectomy:
      results from the Health Professionals Follow-up Study.
AB  - BACKGROUND: Robot-assisted laparoscopic radical prostatectomy (RALP) has become
      increasingly common; however, there have been no nationwide, population-based,
      non-claims-based studies to evaluate differences in outcomes between RALP and
      open radical retropubic prostatectomy (RRP). OBJECTIVE: To determine surgical,
      oncologic, and health-related quality of life (HRQOL) outcomes following RALP and
      RRP in a nationwide cohort. DESIGN, SETTING, AND PARTICIPANTS: We identified 903
      men in the Health Professionals Follow-up Study diagnosed with prostate cancer
      between 2000 and 2010 who underwent radical prostatectomy using RALP (n=282) or
      RRP (n=621) as primary treatment. INTERVENTION: Radical prostatectomy. OUTCOME
      MEASUREMENTS AND STATISTICAL ANALYSIS: We compared patients undergoing RALP or
      RRP across a range of perioperative, oncologic, and HRQOL outcomes. RESULTS AND
      LIMITATIONS: Use of RALP increased during the study period, constituting 85.2% of
      study subjects in 2009, up from 4.5% in 2003. Patients undergoing RALP compared
      to RRP were less likely to have a lymph node dissection (51.5% vs 85.4%;
      p<0.0001), had less blood loss (207.4 ml vs 852.3 ml; p<0.0001), were less likely
      to receive blood transfusions (4.3% vs 30.3%; p<0.0001), and had shorter hospital
      stays (1.8 d vs 2.9 d; p<0.0001). Surgical, oncologic, and HRQOL outcomes did not
      differ significantly among the groups. In multivariate logistic regression
      models, there were no significant differences in 3- or 5-yr recurrence-free
      survival comparing RALP versus RRP (hazard ratios: 0.98 [95% confidence interval
      (CI), 0.46-2.08] and 0.75 [95% CI, 0.18-3.11], respectively). CONCLUSIONS: In a
      nationwide cohort of patients undergoing surgical treatment for prostate cancer,
      RALP was associated with shorter hospital stay, and lower blood loss and
      transfusion rates than RRP. Surgical oncologic and HRQOL outcomes were similar
      between groups. PATIENT SUMMARY: We studied men throughout the United States with
      prostate cancer who underwent surgical removal of the prostate. We found that
      robot-assisted laparoscopic radical prostatectomy resulted in shorter hospital
      stay, less blood loss, and fewer blood transfusions than radical retropubic
      prostatectomy. There were no differences in cancer control or health-related
      quality of life.

PMID- 24582330
TI  - Platelet indices in differential diagnosis of pancreatic neuroendocrine tumors
      from pancreatic adenocarcinomas.

PMID- 24582329
TI  - Hyponatraemia is an independent predictor of in-hospital mortality.
AB  - BACKGROUND: Hyponatraemia increases morbidity and mortality, but the extent to
      which this condition influences mortality independently of other contributing
      factors is unclear. MATERIALS AND METHODS: All hyponatremic patients admitted to
      the internal medicine department during a six month period were included. Medical
      records were reviewed and patients' demographics, underlying disease, cause of
      hyponatremia and in-hospital deaths were noted. Control group consisted of
      patients with normonatremia admitted to the same department during the same
      period matched 1:1 by sex, age and underlying disease. Difference in in-hospital
      mortality rate between the study and control groups was tested by chi-square
      test. Baseline demographics, underlying diseases, cause of hyponatremia and state
      of hyponatremia correction as possible risk factors for mortality were tested in
      a multivariate analysis. RESULTS: The baseline cohort of all admitted patients
      consisted of 2,171 patients. Hyponatraemia was found in 278 (13%) patients (160
      females and 118 males). The three most common causes of hyponatremia included
      gastrointestinal loss (52 patients), decreased oral intake (47 patients), and
      dilution hyponatremia (45 patients). The in-hospital mortality rate in the
      hyponatremic group was significantly higher compared with the control group (22%
      vs 7%, respectively; OR 3.75, 95% CI 2.17-6.48, p<0.0001). In a multivariate
      analysis age above 65 years, dilution hyponatremia, decreased oral intake as
      etiologic factors of hyponatremia, and unsuccessful hyponatremia correction were
      independent factors associated with increased mortality. CONCLUSION:
      Hyponatraemia represents independent factor associated with in-hospital
      mortality. Age above 65 years, failure to correct hyponatremia and some specific
      etiologic factors of hyponatremia are related to increased mortality.

PMID- 24582331
TI  - Glaucoma--diabetes of the brain: a radical hypothesis about its nature and
      pathogenesis.
AB  - Glaucoma is the leading cause of irreversible blindness characterized by
      irremediable loss of retinal ganglion cells. Its risk increases with progressing
      age and elevated intraocular pressure. Studies have established that glaucoma is
      a neurodegenerative disorder in which the damage involves many brain tissues from
      retina to the lateral geniculate nucleus. Despite lot of research, complete
      pathomechanism of glaucoma is not known and there is no treatment available
      except modification of intraocular pressure pharmacologically and/or surgically.
      We here present a hypothesis inspired by studies across many areas of molecular
      and clinical sciences in an integrative manner that leads to a uniquely
      unconventional understanding of this disorder. Our hypothesis postulates that
      glaucoma may possibly be the diabetes of the brain. Based on the remarkable
      similarities between glaucoma and diabetes we propose glaucoma also to be a type
      of diabetes. Glaucoma and diabetes share many aspects from various molecular
      mechanisms to involvement of insulin and possible use of antidiabetics in
      glaucoma therapy. Additionally, Alzheimer's disease has already been proposed to
      be diabetes type-3. We show that Alzheimer's disease is cerebral glaucoma and
      diabetes at the same time which, by transitive property of similarities, again
      leads to our hypothesis that glaucoma is diabetes of the brain. Our proposition
      may lead to appreciation of certain important facets of glaucoma which have
      previously not been given due consideration. It also may lead to an alternative
      classification of diabetes as pancreatic and brain diabetes thereby widening the
      vision arena of the understanding of both these disorders. 

PMID- 24582332
TI  - The putative role of proteolytic pathways in the pathogenesis of Type 1 diabetes
      mellitus: the 'autophagy' hypothesis.
AB  - Autoimmune diseases are a heterogeneous group of disorders affecting different
      organs and tissues. New tools, such as genome-wide association studies, have
      provided evidence for new susceptibility loci and candidate genes in the disease
      process including common susceptibility genes involved in the immunological
      synapse and T cell activation. Close linkages have been found in a number of
      diseases, including ankylosing spondylitis, multiple sclerosis, Crohn's disease
      and insulin-dependent diabetes mellitus (Type 1 diabetes mellitus). Evidence for
      some association with Type 1 diabetes was previously found in the region
      containing 5q15/ERAP1 (endoplasmic reticulum aminopeptidase 1) (rs30187, ARTS1).
      Recent data suggest that in eukaryotic cells in addition to the
      ubiquitin/proteasome system another proteolytic pathway may have a significant
      role in the autoimmunity process, i.e. the autophagic pathway which constitutes
      the principal regulated catabolic process mediated by lysosomes. Autophagy could
      play a role in MHC class I and class II self-antigen presentation at the basis of
      the autoimmunity process. Furthermore cross-talk among different proteolytic
      pathways was recently highlighted i.e. components processed in the
      ubiquitin/proteasome system possibly engaged in autophagic pathways. T1D is an
      autoimmune disease characterised by the destruction of pancreatic beta cells by
      autoreactive T cells. Immunological abnormalities can precede months to years the
      initial symptoms and clinical diagnosis. Our hypothesis suggests that in the
      autoimmune process autophagy can intervene at different levels, during the thymic
      selection process of T lymphocytes causing escape of autoreactive T cells, at the
      initiation stage of the disease, in the preclinical period or subsequently to the
      disease onset having a role at the level of perpetuation of the autoimmunity
      process. Supporting evidence derives from the already reported discovery of
      polymorphisms in autophagy-related genes in patients affected by several
      autoimmune conditions such as Systemic Lupus Erithematosus. In addition
      deregulated autophagy was detected in T cells from lupus-prone mice and also
      found in T cells from patients. Autophagy was found activated in osteoclasts from
      RA patients as demonstrated by the increased expression of Atg7 and Beclin-1. Our
      hypothesis to be unraveled could have, if correct, relevant implications for the
      management of autoimmune conditions such as Type 1 diabetes. In principle, novel
      therapeutic approaches could be established by targeting deregulated autophagy
      offering novel opportunities to personalized medicine in patients affected by the
      disease.

PMID- 24582334
TI  - A communication skills intervention for community healthcare workers reduces
      perceived patient aggression: a pretest-postest study.
AB  - BACKGROUND: Previous studies have shown that healthcare workers experience high
      levels of aggression from patients. Prevention packages to address this have
      received little research support. Communication skills have been shown to
      influence individuals' experience of aggression and are also amenable to
      training. OBJECTIVES: This study aims to deliver a communication skills training
      package that will reduce the experience of aggression in the workplace for
      healthcare workers. DESIGN: An interactive, multimedia communication skills
      package was developed that would be suitable for community healthcare workers.
      The training consisted of four workshops, including teaching, discussion and DVD
      illustrative examples. These were based on research and clinical experience.
      SETTINGS: This intervention was delivered in two community care organisations
      over several months. PARTICIPANTS: Fifty-six community healthcare workers took
      part in the trial in small groups. There were 46 females and 10 males with a
      median age of 45-54 years. METHODS: For each group a series of four communication
      skills workshops were given. Measurements of perceived aggression and wellbeing
      were taken before the workshops, at the end of the workshops, one month after and
      two months after. RESULTS: Results show statistically significant reductions in
      perceived aggression one and two months after baseline measures (p<0.01). Results
      also suggest reductions in distress and increases in general mental wellness
      (p<0.01). Evaluation of the programme by participants was positive. CONCLUSIONS:
      A brief communication skills training programme is both enjoyable and shows
      decreases in perceived aggression, distress, and increases in general mental
      wellness. A full RCT of this intervention is warranted.

PMID- 24582333
TI  - Discovery of unconventional kinetochores in kinetoplastids.
AB  - The kinetochore is the macromolecular protein complex that directs chromosome
      segregation in eukaryotes. It has been widely assumed that the core kinetochore
      consists of proteins that are common to all eukaryotes. However, no conventional
      kinetochore components have been identified in any kinetoplastid genome, thus
      challenging this assumption of universality. Here, we report the identification
      of 19 kinetochore proteins (KKT1-19) in Trypanosoma brucei. The majority is
      conserved among kinetoplastids, but none of them has detectable homology to
      conventional kinetochore proteins. These proteins instead have a variety of
      features not found in conventional kinetochore proteins. We propose that
      kinetoplastids build kinetochores using a distinct set of proteins. These
      findings provide important insights into the longstanding problem of the position
      of the root of the eukaryotic tree of life.

PMID- 24582335
TI  - Effort training in Parkinson's disease: a systematic review.
AB  - OBJECTIVE: Physical therapy strategies have recently proved their efficacy in the
      field of Parkinson's disease management. The purpose of this paper was to access
      the efficacy and the limits of aerobic training and strength training included in
      physical rehabilitation programs and to define practical modalities. METHOD: A
      comprehensive search on Pubmed and Cochrane databases was made. RESULTS: Five
      literature revues and thirty one randomised trials have been selected. Exercise
      training improves aerobic capacities, muscle strength, walking, posture and
      balance parameters. Rehabilitation programs should begin as soon as possible,
      last several weeks and be repeated. They should include aerobic training on
      bicycle or treadmill and a muscle strengthening program. CONCLUSION: There is
      evidence that aerobic and strength training improve physical habilities of
      patients suffering from Parkinson's Disease. Rehabilitation programs should be
      discussed with the patient, taking in account his difficulties and his physical
      capacities. Two questions are debatable: exercise intensity and phase ON / phase
      OFF timing.

PMID- 24582336
TI  - Radiolysis and photolysis studies on active transient species of berberine.
AB  - In this paper, the photochemical and photobiological characters of the active
      radicals of berberine (BBR) was investigated for finding an efficient and safe
      photosensitizer with highly active transient products using in Photodynamic
      therapy (PDT) study. The active species of BBR was generated and identified by
      using pulse radiolysis method. In neutral aqueous solution, BBR react with
      hydrated electron and hydroxyl radical, forming the radical anion and neutral
      radical of BBR, and the related reaction rates were determined as 3.5*10(10) and
      6.7*10(9) M(-1) s(-1), respectively. Further, the capability of BBR to
      photosensitize DNA cleavage was testified by laser flash photolysis (LFP) method,
      the results demonstrated that BBR neutral radical could react with guanine
      mononucleotide (K=1.9*10(9) M(-1) s(-1)) via electron transfer to give the
      guanine neutral radical. Additionally BBR selective cleavage single and double
      strand DNA at guanine moiety was observed. Finally, combining with the
      thermodynamic calculation, the possible photodamage mechanism of dGMP and DNA
      induced by BBR was clarified.

PMID- 24582337
TI  - Dipole-dipole interactions in solution mixtures probed by two-dimensional
      synchronous spectroscopy based on orthogonal sample design scheme.
AB  - Two-dimensional (2D) synchronous spectroscopy together with a new approach called
      "Orthogonal Sample Design Scheme" was used to study the dipole-dipole
      interactions in two representative ternary chemical systems (N,N
      dimethyllformamide (DMF)/CH3COOC2H5/CCl4 and C60/CH3COOC2H5/CCl4). For the first
      system, dipole-dipole interactions among carbonyl groups from DMF and CH3COOC2H5
      are characterized by using the cross peak in 2D Fourier Transform Infrared
      Radiation (FT-IR) spectroscopy. For the second system, intermolecular interaction
      among pi-pi transition from C60 and vibration transition from the carbonyl band
      of ethyl acetate is probed by using 2D spectra. The experimental results
      demonstrate that "Orthogonal Sample Design Scheme" can effectively remove
      interfering part that is not relevant to intermolecular interaction. Additional
      procedures are carried out to preclude the possibilities of producing interfering
      cross peaks by other reasons, such as experimental errors. Dipole-dipole
      interactions that manifest in the form of deviation from the Beer-Lambert law
      generate distinct cross peaks visualized in the resultant 2D synchronous spectra
      of the two chemical systems. This work demonstrates that 2D synchronous spectra
      coupled with orthogonal sample design scheme provide us an applicable
      experimental approach to probing and characterizing dipole-dipole interactions in
      complex molecular systems. 

PMID- 24582338
TI  - Myelin, myelination, and corresponding magnetic resonance imaging changes.
AB  - Accurate diagnosis of white matter diseases requires a thorough understanding of
      white matter maturation. These maturational changes are complex and require
      knowledge of the histologic background and time course of development. This
      article reviews the in vivo magnetic resonance (MR) appearance of myelination
      with emphasis on the appearance of different regions of the brain using various
      pulse sequences at different developmental time points. The appearance of white
      matter, using the MR pulse sequences that have been shown to be most useful
      during the stages of myelination, is also discussed. 

PMID- 24582339
TI  - A pattern approach to focal white matter hyperintensities on magnetic resonance
      imaging.
AB  - Evaluation of focal white matter hyperintensities on magnetic resonance imaging
      in any age group is always challenging because the cause of these
      hyperintensities varies extensively. Understanding the clinical presentation,
      pathophysiology, and associated imaging findings can allow the radiologist to
      limit the differential diagnosis. A specific imaging approach including age,
      pattern of distribution, signal characteristics on various sequences, enhancement
      pattern, and other ancillary findings helps to identify a correct cause for these
      hyperintensities. This article provides a pattern approach to differentiate
      various common and a few uncommon diseases presenting as focal white matter
      hyperintensities. 

PMID- 24582340
TI  - An imaging approach to diffuse white matter changes.
AB  - White matter disorders represent a large, heterogeneous group of disorders that
      span the continuum of congenital metabolic disorders to acquired processes, such
      as chronic ischemic microvascular white matter disease. Magnetic resonance
      imaging has dramatically revolutionized the diagnostic evaluation of patients
      with these disease processes. 

PMID- 24582341
TI  - Imaging manifestations of the leukodystrophies, inherited disorders of white
      matter.
AB  - The leukodystrophies are a diverse set of inherited white matter disorders and
      are uncommonly encountered by radiologists in everyday practice. As a result, it
      is challenging to recognize these disorders and to provide a useful differential
      for the referring physician. In this article, leukodystrophies are reviewed from
      the perspective of 4 imaging patterns: global myelination delay,
      periventricular/deep white matter predominant, subcortical white matter
      predominant, and mixed white/gray matter involvement patterns. Special emphasis
      is placed on pattern recognition and unusual combinations of findings that may
      suggest a specific diagnosis. 

PMID- 24582342
TI  - Advances in multiple sclerosis and its variants: conventional and newer imaging
      techniques.
AB  - Multiple sclerosis (MS) and its variants are inflammatory as well as
      neurodegenerative diseases that diffusely affect the central nervous system
      (CNS). There is a poor correlation between traditional imaging findings and
      symptoms in patients with MS. Current research in conventional magnetic resonance
      (MR) imaging of MS and related diseases includes optimization of hardware and
      pulse sequences and the development of automated and semiautomated techniques to
      measure and quantify disease burden. Advanced nonconventional MR techniques such
      as diffusion tensor and functional MR imaging probe the changes found in the CNS,
      and correlate these findings with clinical measures of disease. 

PMID- 24582343
TI  - Secondary demyelination disorders and destruction of white matter.
AB  - Demyelinating disorders of the central nervous system are characterized by the
      breakdown of myelin, with or without preservation of the associated axons.
      Primary demyelinating diseases typically involve loss of myelin with relative
      sparing of axons. Secondary demyelinating disorders represent a spectrum of white
      matter disease characterized by damage to neurons or axons with the resultant
      breakdown of myelin. The pathologic changes seen in secondary demyelinating
      disorders are varied, ranging from pure demyelination to necrosis with subsequent
      demyelination. Secondary demyelinating diseases are associated with a wide
      variety of conditions, including infections/vaccinations, nutritional/vitamin
      deficiencies, chemical agents, genetic abnormalities, and vascular insult. 

PMID- 24582344
TI  - Viral infections and white matter lesions.
AB  - This article discusses imaging findings in virus-related infectious and
      noninfectious encephalitis/encephalopathy with white matter involvement, as well
      as the differential diagnosis based on the characteristic distribution. Acute
      viral encephalitis/encephalopathy is a medical emergency. Prompt introduction of
      treatment has a significant influence on survival and the extent of permanent
      brain injury. Differentiation between infectious and noninfectious central
      nervous system involvement is paramount. Neuroimaging provides many clues for the
      specific diagnosis. Understanding the underlying disorder and pathophysiology is
      important for the interpretation of the images and therefore the treatment. 

PMID- 24582345
TI  - Neuroimaging of vascular dementia.
AB  - When atrophy is seen on imaging in adult patients, it does not necessarily
      represent Alzheimer disease. Many cases of dementia or cognitive decline could be
      caused by reversible or preventable diseases, such as vascular dementia. This
      article familiarizes the physician with various types of vascular lesions leading
      to dementia and cognitive decline and their imaging appearances. Neuroimaging
      plays an important role in identifying vascular lesions of the brain early, even
      before the clinical manifestation of the cognitive decline symptoms and, thus,
      can help to prevent or delay the symptoms related to the various vascular
      pathologic conditions. 

PMID- 24582346
TI  - Metabolic white matter diseases and the utility of MR spectroscopy.
AB  - Magnetic resonance spectroscopy (MRS) can be useful as an adjuvant diagnostic
      tool to traditional MR imaging of the brain. MRS can provide both quantitative
      and qualitative information about white matter pathologic abnormality. It is
      important to interpret MRS in conjunction with other clinical factors including
      but not limited to additional diagnostic neuroimaging, history and physical
      examination findings, and genetics. 

PMID- 24582347
TI  - Diffusion tensor imaging of cerebral white matter: technique, anatomy, and
      pathologic patterns.
AB  - Diffusion tensor imaging is a magnetic resonance imaging technique that provides
      insight into the anatomy and integrity of white matter pathways in the brain.
      Further processing of these data can help map individual tracts, which can aid in
      surgical planning. Understanding the basics of this technique can improve
      characterization of white matter development and disorders. 

PMID- 24582348
TI  - Imaging approach to the cord T2 hyperintensity (myelopathy).
AB  - In clinically suspected cases of myelopathy, magnetic resonance imaging without
      and with gadolinium remains the modality of choice. The first and best imaging
      approach in the evaluation of myelopathy is to identify whether the cause of
      myelopathy is compressive or noncompressive. The commonest imaging finding in
      myelopathy is either focal or diffuse cord hyperintensity on the T2-weighted
      magnetic resonance images. Detailed clinical history, acuity of symptoms (acute
      vs insidious onset), distribution of the signal abnormalities, including length
      of cord involvement, specific tract involvement, and the region of the spinal
      cord that is affected, are very useful in making the diagnosis. 

PMID- 24582349
TI  - Imaging of white matter lesions.

PMID- 24582350
TI  - Acoustic power dependences of sonoluminescence and bubble dynamics.
AB  - The decreasing effect of sonoluminescence (SL) in water at high acoustic powers
      was investigated in relation to bubble dynamics and acoustic emission spectra.
      The intensity of SL was measured in the power range of 1-18W at 83.8kHz for open
      end (free liquid surface and film-covered surface) and fixed-end boundaries of
      sound fields. The power dependence of the SL intensity showed a maximum and then
      decrease to zero for all the boundaries. Similar results were obtained for
      sonochemiluminescence in luminol solution. The power dependence of the SL
      intensity was strongly correlated with the bubble dynamics captured by high-speed
      photography at 64kfps. In the low-power range where the SL intensity increases,
      bubble streamers were observed and the population of streaming bubbles increased
      with the power. At powers after SL maximum occurred, bubble clusters came into
      existence. Upon complete SL reduction, only bubble clusters were observed. The
      subharmonic in the acoustic emission spectra increased markedly in the region
      where bubble clusters were observed. Nonspherical oscillations of clustering
      bubbles may make a major contribution to the subharmonic. 

PMID- 24582351
TI  - Can you pull it off? Appearance modifying behaviours adopted by wig users with
      alopecia in social interactions.
AB  - In the academic and medical literature on alopecia, wigs (hair prostheses) are
      typically recommended as a coping strategy: a device to camouflage, conceal, or
      cover hair loss, and cope with the psychological impact of a dramatic change in
      body image. This paper used Goffman's (1959) theory of impression management to
      demonstrate (a) the social significance of self-presentation, and (b) how adults
      with alopecia managed their wig use in their daily lives. Data from 14
      interviews, two focus groups and six video diaries with 22 Caucasian adults (19
      females, 3 males; 29-74 years, SD=13.75) with alopecia in Scotland were analysed
      using discursive psychology. The analysis detailed how participants managed their
      wig use and behaviours in relation to social interaction with different
      categories of people. The paper raises concerns about health and medical
      discourse about wigs as a coping mechanism, and provides practical suggestions
      for wig users in social settings. 

PMID- 24582352
TI  - Quantitative evaluation of the major determinants of human gait.
AB  - Accurate knowledge of the isolated contributions of joint movements to the three
      dimensional displacement of the center of mass (COM) is fundamental for
      understanding the kinematics of normal walking and for improving the treatment of
      gait disabilities. Saunders et al. (1953) identified six kinematic mechanisms to
      explain the efficient progression of the whole-body COM in the sagittal,
      transverse, and coronal planes. These mechanisms, referred to as the major
      determinants of gait, were pelvic rotation, pelvic list, stance knee flexion,
      foot and knee mechanisms, and hip adduction. The aim of the present study was to
      quantitatively assess the contribution of each major gait determinant to the
      anteroposterior, vertical, and mediolateral displacements of the COM over one
      gait cycle. The contribution of each gait determinant was found by applying the
      concept of an 'influence coefficient', wherein the partial derivative of the COM
      displacement with respect to a prescribed determinant was calculated. The
      analysis was based on three-dimensional measurements of joint angular
      displacements obtained from 23 healthy young adults walking at slow, normal and
      fast speeds. We found that hip flexion, stance knee flexion, and ankle-foot
      interaction (comprised of ankle plantarflexion, toe flexion and the displacement
      of the center of pressure) are the major determinants of the displacements of the
      COM in the sagittal plane, while hip adduction and pelvic list contribute most
      significantly to the mediolateral displacement of the COM in the coronal plane.
      Pelvic rotation and pelvic list contribute little to the vertical displacement of
      the COM at all walking speeds. Pelvic tilt, hip rotation, subtalar inversion, and
      back extension, abduction and rotation make negligible contributions to the
      displacements of the COM in all three anatomical planes. 

PMID- 24582353
TI  - Reply to letter to the editor: "IUD fracture mechanism".

PMID- 24582354
TI  - Impact of partial participation in integrated family planning training on medical
      knowledge, patient communication and professionalism.
AB  - INTRODUCTION: Obstetrics and gynecology residency programs are required to
      provide access to abortion training, but residents can opt out of participating
      for religious or moral reasons. Quantitative data suggest that most residents who
      opt out of doing abortions participate and gain skills in other aspects of the
      family planning training. However, little is known about their experience and
      perspective. METHODS: Between June 2010 and June 2011, we conducted
      semistructured interviews with current and former residents who opted out of some
      or all of the family planning training at ob-gyn residency programs affiliated
      with the Kenneth J. Ryan Residency Training Program in Abortion and Family
      Planning. Residents were either self-identified or were identified by their Ryan
      Program directors as having opted out of some training. The interviews were
      transcribed and coded using modified grounded theory. RESULTS: Twenty-six
      physicians were interviewed by telephone. Interviewees were from geographically
      diverse programs (35% Midwest, 31% West, 19% South/Southeast and 15%
      North/Northeast). We identified four dominant themes about their experience: (a)
      skills valued in the family planning training, (b) improved patient-centered
      care, (c) changes in attitudes about abortion and (d) miscommunication as a
      source of negative feelings. DISCUSSION: Respondents valued the ability to
      partially participate in the family planning training and identified specific
      aspects of their training which will impact future patient care. Many of the
      effects described in the interviews address core competencies in medical
      knowledge, patient care, communication and professionalism. We recommend that
      programs offer a spectrum of partial participation in family planning training to
      all residents, including residents who choose to opt out of doing some or all
      abortions. IMPLICATIONS: Learners who morally object to abortion but participate
      in training in family planning and abortion, up to their level of comfort, gain
      clinical and professional skills. We recommend that trainers should offer a range
      of participation levels to maximize the educational opportunities for these
      learners.

PMID- 24582355
TI  - Mechanical and toxicological evaluation of concrete artifacts containing waste
      foundry sand.
AB  - The creation of metal parts via casting uses molds that are generally made from
      sand and phenolic resin. The waste generated after the casting process is called
      waste foundry sand (WFS). Depending on the mold composition and the casting
      process, WFS can contain substances that prevent its direct emission to the
      environment. In Brazil, this waste is classified according to the Standard ABNT
      NBR 10004:2004 as a waste Class II (Non-Inert). The recycling of this waste is
      limited because its characteristics change significantly after use. Although the
      use (or reuse) of this byproduct in civil construction is a technically feasible
      alternative, its effects must be evaluated, especially from mechanical and
      environmental points of view. Thus, the objective of this study is to investigate
      the effect of the use of WFS in the manufacture of cement artifacts, such as
      masonry blocks for walls, structural masonry blocks, and paving blocks. Blocks
      containing different concentrations of WFS (up to 75% by weight) were produced
      and evaluated using compressive strength tests (35 MPa at 28 days) and toxicity
      tests on Daphnia magna, Allium cepa (onion root), and Eisenia foetida
      (earthworm). The results showed that there was not a considerable reduction in
      the compressive strength, with values of 35 +/- 2 MPa at 28 days. The toxicity
      study with the material obtained from leaching did not significantly interfere
      with the development of D. magna and E. foetida, but the growth of the A. cepa
      species was reduced. The study showed that the use of this waste in the
      production of concrete blocks is feasible from both mechanical and environmental
      points of view.

PMID- 24582356
TI  - Investigation of chemical modifications of micro- and macromolecules in bio-oil
      during hydrodeoxygenation with Pd/C catalyst in supercritical ethanol.
AB  - Miscanthus bio-oil was subjected to hydrodeoxygenation (HDO) with Pd/C at
      different temperatures (250, 300 and 350 degrees C) and times (30, 45 and 60 min)
      to investigate the chemical modification of micro- and macromolecules in bio-oil.
      Four main products - char, gas and two immiscible oils (light and heavy oil) -
      were obtained from the HDO reaction. Yields of heavy oil as a targeting product
      of HDO varied from 60% to 13%, whereas those of gas and char were ranged from 7%
      to 36% and 6% to 17%, respectively. Water content was estimated to<1% and heating
      value was 26-31 MJ kg(-1). Reduction of unstable oxygen-containing compounds such
      as acids (2-hydroxy-butanoic acid), aldehydes (furfural), alcohols (butanedial)
      and sugars (levoglucosan) were characteristic in heavey oil. Apart from
      hydrogenation and deoxygenation, micromolecules in bio-oil were plausibly
      modified to stable ketones, esters and saturated components via demethoxylation,
      dealkylation, decarbonylation, dehydroxylation and ring opening. Macromolecular
      lignin fragments (referred to as pyrolytic lignins in bio-oil and phenol polymers
      in heavy oil) were extracted and subjected to several analyses. Approximately 60%
      of the pyrolytic lignins were decomposed into low molecular weight compounds
      during HDO reaction. Moreover, essential functional groups, OCH3 and phen-OH
      groups attached to pyrolytic lignin, were severely modified during HDO reaction.

PMID- 24582357
TI  - Toxicity of copper oxide nanoparticles in the blue mussel, Mytilus edulis: a
      redox proteomic investigation.
AB  - Relatively little is known about the fate and effects of nanomaterials even in
      relatively simple organisms such as Mytilus edulis. Here, copper oxide
      nanoparticles (CuO NP) are shown to induce dose-dependent toxic effects at the
      biochemical, physiological and tissue levels in the blue mussel. Stable CuO NP
      suspensions were sized by differential light scattering and nanoparticle tracking
      analysis to yield average particle diameters of approximately 100 nm. These were
      administered to M. edulis, at doses of 400, 700 and 1000 ppb. Ingested copper was
      predominantly located in the gill tissue with small amounts in digestive gland.
      Fifteen coomassie-stained spots were excised from two dimensional gel
      electrophoresis separations of gill tissue extacts and identified by peptide mass
      fingerprinting. These contained six unique proteins (alpha- and beta-tubulin,
      actin, tropomyosin, triosephosphate isomerase and Cu-Zn superoxide dismutase). Of
      these, two spots (actin and triosephosphate isomerase) showed decreased protein
      thiols while three (alpha-tubulin, tropomyosin and Cu-Zn superoxide dismutase)
      showed increased carbonylation which is indicative of protein oxidation of
      cytoskeleton and enzymes in response to CuO NP. The neutral red retention time
      (NRRT) assay revealed toxicity due to the CuO NPs which was comparable with toxic
      metal oxide nanoparticles such as chromium and cobalt. In contrast, non-toxic
      titanium and gold metal oxide nanoparticles gave no NRRT effects at similar NP
      concentrations. Histology revealed deposition of pigmented brown cells in
      response to CuO NP, located predominantly along the mantle and gill margin but
      also lining digestive tubules and some of the sinuses and distributed throughout
      the connective tissue and in the adductor muscle.

PMID- 24582358
TI  - Distribution and bioconcentration of endocrine disrupting chemicals in surface
      water and fish bile of the Pearl River Delta, South China.
AB  - The distribution and bioconcentration of endocrine disrupting chemicals (EDCs) in
      water, algae, and wild carp bile of the Pearl River Delta (PRD), South China were
      investigated. 4-tert octylphenol (OP), 4-nonylphenol (NP), and bisphenol A (BPA)
      (unit, ng L(-1)) in water were in the ranges of 1-14, 117-865, and 4-377, those
      (ng g(-1) dry weight) in algae were in the ranges of 2-13, 53-282, and 16-94, and
      those (ng g(-1)) in carp bile were in the ranges of 14-39, 950-4648, 70-1020,
      respectively. Estrone (E1) and 17alpha-ethinylestradiol (EE2) in water ranged
      from <LOQ to 1.58 ng L(-1) and from <LOQ to 3.43 ng L(-1), respectively. In bile
      and algae, E1 ranged from nd to 30 ng g(-1), but EE2 was not detected. The E2
      activity equivalents (EEQs) ranged from 1.20 to 10.97 ng g(-1) in carp bile and
      from 0.07 to 8.06 ng L(-1) in water. The EEQs in carp bile were significantly
      related to those in water, illustrating that occurrence of EDCs in carp bile can
      reflect that in ambient water in the PRD region. The bioconcentration factors
      (BCF, L kg(-1)) of OP, NP, BPA, and E1 in algae were in the ranges of 482-7251,
      131-740, 2846-12979, and undetectable, respectively, and those in carp bile were
      in the ranges of 1500-12960, 1648-11137, 3583-14178, and 13208-39623,
      respectively. The phenolic EDCs can be accumulated by wild carp bile and algae in
      the investigated aquatic ecosystems, which is also affected by the degree of the
      eutrophication. This study for the first time reported EDCs in carp bile and
      algae collected from the PRD, China.

PMID- 24582359
TI  - Levels and distribution of hexabromocyclododecane and its lower brominated
      derivative in Japanese riverine environment.
AB  - Hexabromocyclododecane (HBCD) and its lower brominated derivatives were measured
      in both surface water and sediment samples from three Japanese rivers; Tsurumi
      River, Yodo River, and Kuzuryu River. The concentration level of ?HBCD (sum of
      alpha-, beta-, and gamma-HBCD) was in the order of Kuzuryu>Yodo>Tsurumi Rivers,
      reflective of the different emission sources for each basin. The highest ?HBCD
      concentration (7800 ng g(-1)dw) was detected in the sediment sample from the
      Kuzuryu River that receives effluents from textile industries, which use HBCD in
      flame retardant finishes. A different diastereomeric pattern of alpha-, beta-,
      and gamma-HBCD of each river was investigated, indicating the level of HBCD in
      these rivers is directly influenced by emission source. Enantiomer fractions of
      HBCDs in water and sediment samples were also determined. Racemic mixtures were
      observed in the water samples, whereas enantiomeric enrichment of (-) gamma-HBCD
      and (+) alpha-HBCD was observed in the sediment samples. Some lower brominated
      HBCD derivatives such as pentabromocyclododecenes were detected in both the water
      and sediment samples, and their concentration ranged from below the detection
      limit to 15 ng L(-1) and 20 ng g(-1)dw, respectively.

PMID- 24582360
TI  - Comparisons of the reactivity, reusability and stability of four different zero
      valent iron-based nanoparticles.
AB  - Our previous reports showed that nano zero-valent iron (nZVI), steel pickle
      liquor for the synthesis of nZVI (S-nZVI), nZVI immobilised in mesoporous silica
      microspheres (SiO2@FeOOH@Fe) and nano Ni/Fe bimetallic particles (Ni/Fe) have
      been proved to show good property for elimination of polybrominated diphenyl
      ethers (PBDEs). However, it is necessary to compare their reactivity, reusability
      and stability when applied to in situ remediation. In this study, the
      performances of different iron-based nanoparticles were compared through
      reusability, sedimentation and iron dissolution experiments. The SiO2@FeOOH@Fe
      and Ni/Fe nanoparticles were shown to have higher reusability and stability, as
      they could be reused more than seven times, and that the SiO2@FeOOH@Fe can
      effectively avoid leaching iron ions into the solution and causing secondary
      pollution in the reaction. This study may serve as a reference for PBDE
      remediation in the future. 

PMID- 24582361
TI  - Testing of various membranes for use in a novel sediment porewater isolation
      chamber for infaunal invertebrate exposure to PCBs.
AB  - In benthic sediment bioassays, determining the relative contribution to exposure
      by contaminants in overlying water, porewater, and sediment particles is
      technically challenging. The purpose of the present study was to assess the
      potential for membranes to be utilized as a mechanism to allow freely dissolved
      hydrophobic organic contaminants into a pathway isolation exposure chamber (PIC)
      while excluding all sediment particles and dissolved organic carbon (DOC). This
      investigation was conducted in support of a larger effort to assess contaminant
      exposure pathways to benthos. While multiple passive samplers exist for
      estimating concentrations of contaminants in porewater such as those using solid
      phase micro extraction (SPME) and polyoxymethylene (POM), techniques to
      effectively isolate whole organism exposure to porewater within a sediment system
      are not available. We tested the use of four membranes of different pore sizes
      (0.1-1.2MUm) including nylon, polycarbonate, polyethylsulfone, and
      polytetrafluoroethylene with a hydrophilic coating. Exposures included both
      diffusion of radiolabeled and non-labeled contaminants across membranes from
      aqueous, sediment slurry, and whole sediment sources to assess and evaluate the
      best candidate membrane. Data generated from the present study was utilized to
      select the most suitable membrane for use in the larger bioavailability project
      which sought to assess the relevance of functional ecology in bioavailability of
      contaminated sediments at remediation sites. The polytetrafluoroethylene membrane
      was selected for use in the PIC, although exclusion of dissolved organic carbon
      was not achieved. 

PMID- 24582362
TI  - Metabolism of bisphenol A by hyper lignin-degrading fungus Phanerochaete sordida
      YK-624 under non-ligninolytic condition.
AB  - Recently, we reported the conversion of bisphenol A (BPA) to 4-(2-(4
      hydroxyphenyl)propan-2-yl)benzene-1,2-diol (hydroxy-BPA) by hyper lignin
      degrading fungus Phanerochaete sordida YK-624 under non-ligninolytic condition.
      In the present study, the metabolism of hydroxy-BPA by P. sordida YK-624 was
      demonstrated under non-ligninolytic condition. Under these conditions,
      approximately 66% of hydroxy-BPA was degraded after 7 d of incubation. High
      resolution electrospray ionization mass spectra and nuclear magnetic resonance
      analyses of the metabolites isolated from the culture broth indicated that
      hydroxy-BPA was metabolized to 4-(2-(4-hydroxyphenyl)propan-2-yl)-2-methoxyphenol
      (methoxy-BPA) and to 4-(2-(3,4-dimethoxyphenyl)propan-2-yl)phenol (dimethoxy-BPA)
      by sequential methylation events. These metabolites showed reduced estrogenic
      activity compared to BPA. These results suggested that the hydroxy BPA is
      methylated to two low toxic-methylation metabolites. 

PMID- 24582364
TI  - Photolysis of low concentration H2S under UV/VUV irradiation emitted from high
      frequency discharge electrodeless lamps.
AB  - The photolysis of low concentration of H2S malodorous gas was studied under UV
      irradiation emitted by self-made high frequency discharge electrodeless lamp with
      atomic mercury lines at 185/253.7nm. Experiments results showed that the removal
      efficiency (etaH2S) of H2S was decreased with increasing initial H2S
      concentration and increased slightly with gas residence time. etaH2S was
      increased dramatically with relative humidity from<5% to 43% while the
      concentration of oxygen in gas environments affected the removal of H2S. The
      mechanisms for direct and indirect photolysis (generation of ozone) were
      illustrated by the experimental results on photolysis of H2S under argon
      environments and ozonation of H2S under air environments, respectively. The
      overall etaH2S by photolysis is higher than the combination of etaH2S by direct
      photolysis and ozonation, suggesting that hydroxyl radical-mediated indirect
      photolysis played an important role during photolysis processes. The main
      photolysis product was confirmed to be SO4(2-) with ion chromatograph. 

PMID- 24582363
TI  - Carbon disulfide induces rat testicular injury via mitochondrial apoptotic
      pathway.
AB  - Carbon disulfide (CS2), one of the most important volatile organic chemicals, was
      shown to have serious impairment to male reproductive system. But the underline
      mechanism is still unclear. In the present study, we aim to investigate the male
      germ cell apoptosis induced by CS2 exposure alone and by co-administration with
      cyclosporin A (CsA), which is the inhibitor of membrane permeability transition
      pore (MPTP). It was shown that CS2 exposure impaired ultrastructure of germ
      cells, increased the numbers of apoptotic germ cells, accumulated intracellular
      level of calcium, elevated ROS level, and increased activities of complexes of
      respiratory chain. Meanwhile, exposure to CS2 dramatically decreased the
      mitochondrial transmembrane potential (DeltaPsim) and levels of ATP and MPTP
      opening. Exposure to CS2 can also cause a significantly dose-dependent increase
      in the expression levels of Bax, Cytc, Caspase-9, and Caspase-3, but decreased
      the expression level of Bcl-2. Moreover, co-administration of CsA with CS2 can
      reverse or alleviate the above apoptotic damage effects of CS2 on testicular germ
      cells. Taken together, our findings suggested that CS2 can cause damage to
      testicular germ cells via mitochondrial apoptotic pathway, and MPTP play a
      crucial role in this process. 

PMID- 24582366
TI  - Destruction behavior of hexabromocyclododecanes during incineration of solid
      waste containing expanded and extruded polystyrene insulation foams.
AB  - Hexabromocyclododecanes (HBCDs) have been used for flame retardation mainly in
      expanded polystyrene (EPS) and extruded polystyrene (XPS) insulation foams.
      Controlled incineration experiments with solid wastes containing each of EPS and
      XPS were conducted using a pilot-scale incinerator to investigate the destruction
      behavior of HBCDs and their influence on the formation of polybrominated dibenzo
      p-dioxins and dibenzofurans (PBDD/DFs). EPS and XPS materials were respectively
      blended with refuse derived fuel (RDF) as input wastes for incineration.
      Concentrations of HBCDs contained in the EPS- and XPS-added RDFs, were 140 and
      1100 mg kg(-1), respectively. In which gamma-HBCD was dominant (68% of the total
      HBCD content) in EPS-added RDF and alpha-HBCD accounted for 73% of the total
      HBCDs in XPS-added RDF. During the incineration experiments with EPS and XPS,
      primary and secondary combustion zones were maintained at temperatures of 840 
      degrees C and 900  degrees C. The residence times of waste in the primary
      combustion zone and flue gas in the secondary combustion zone was 30 min and
      three seconds, respectively. HBCDs were steadily degraded in the combustion
      chambers and alpha-, beta-, and gamma-HBCD behaved similarly. Concentration
      levels of the total HBCDs in the bag filter exit gas for the two experiments with
      EPS and XPS were 0.7 and 0.6ngmN(-3), respectively. HBCDs were also not detected
      (<0.2 ng g(-1)) in the bottom and fly ash samples. From the obtained results, it
      was calculated that HBCDs were sufficiently destroyed in the whole incineration
      process with destruction efficiencies of more than 99.9999 for both of EPS and
      XPS cases. For PBDD/DFs, the levels detected in the bottom and fly ash samples
      were very low (0.028 ng g(-1) at maximum). In the case of XPS-added experiment,
      2,3,7,8-TeBDD and 2,3,7,8-TeBDF were determined in the flue gas at levels (0.05
      0.07 ng mN(-3)) slightly over the detection limits in the environmental emission
      gas samples, suggesting HBCDs in XPS are possibly a precursor of detected
      PBDD/DFs. Operational care should be taken when the ratio of HBCD-containing
      polystyrene is increased in the input wastes just to make sure of formation
      prevention and emission control of PBDD/DFs. The concentrations and congener
      patterns of PCDD/DFs and dl-PCBs in the samples during the three experiments were
      not affected by an addition of HBCDs.

PMID- 24582365
TI  - Endocrine disruption effects of long-term exposure to perfluorodecanoic acid
      (PFDA) and perfluorotridecanoic acid (PFTrDA) in zebrafish (Danio rerio) and
      related mechanisms.
AB  - Perfluoroalkyl acids (PFAAs) have been frequently detected in both the
      environment and biota, however the endocrine disruption potentials and underlying
      mechanism of long-chain PFAAs have not yet been fully understood in fish. In the
      present study, the effects of perfluorodecanoic acid (PFDA) and
      perfluorotridecanoic acid (PFTrDA) on sex steroid hormones and expression of mRNA
      of selected genes in hypothalamic-pituitary-gonad (HPG) axis were evaluated after
      120 d exposure of zebrafish. In addition, production of sex hormones and
      transcription of steroidogenic genes were measured after in vitro exposure of
      H295R cells for 48 h. Exposure to PFTrDA resulted in reduced production of
      testosterone (T) along with lesser expression of CYP17A mRNA in H295R cells. In
      zebrafish, significant up-regulation of vtg1 was observed in males exposed to
      PFDA, whereas down-regulation was observed in females exposed to PFTrDA. In male
      zebrafish, concentrations of 17beta-estradiol (E2) were significantly increased
      at 0.01 mg L(-1) PFTrDA. Significant increases in ratios of E2/T and E2/11
      ketotestosterone (11-KT) were observed in male zebrafish after exposure to PFDA
      or PFTrDA, indicating estrogenic potentials of these compounds. The results of
      this study showed that long-term exposure to PFDA or PFTrDA could modulate sex
      steroid hormone production and related gene transcription of the HPG axis in a
      sex-dependent manner. Consequences of endocrine disruptions in reproduction
      performances of the fish warrant further investigation.

PMID- 24582367
TI  - The author responds.

PMID- 24582368
TI  - Bedside ultrasonography as a diagnostic tool for the fifth metatarsal fractures:
      methodological concern in reliability analysis.

PMID- 24582369
TI  - Anodal transcranial direct current stimulation alters elbow flexor muscle
      recruitment strategies.
AB  - BACKGROUND: Transcranial direct current stimulation (tDCS) is known to reliably
      alter motor cortical excitability in a polarity dependent fashion such that
      anodal stimulation increases cortical excitability and cathodal stimulation
      inhibits cortical excitability. However, the effect of tDCS on agonist and
      antagonist volitional muscle activation is currently not known. OBJECTIVE: This
      study investigated the effect of motor cortical anodal tDCS on EMG/force
      relationships of biceps brachii (agonist) and triceps brachii (antagonist) using
      surface electromyography (EMG). METHODS: Eighteen neurologically intact adults (9
      tDCS and 9 controls) participated in this study. EMG/force relationships were
      established by having subjects perform submaximal isometric contractions at
      several force levels (12.5%, 25%, 37.5%, and 50% of maximum). RESULTS: Results
      showed that anodal tDCS significantly affected the EMG/force relationship of the
      biceps brachii muscle. Specifically, anodal tDCS increased the magnitude of
      biceps brachii activation at 37.5% and 50% of maximum. Anodal tDCS also resulted
      in an increase in the peak force and EMG values during maximal contractions as
      compared to the control condition. EMG analyses of other elbow muscles indicated
      that the increase in biceps brachii activation after anodal tDCS was not related
      to alterations in synergistic or antagonistic muscle activity. CONCLUSIONS: Our
      results indicate that anodal tDCS significantly affects the voluntary EMG/force
      relationship of the agonist muscles without altering the coactivation of the
      antagonistic muscles. The most likely explanation for the observed greater EMG
      per unit force after anodal tDCS appears to be related to alterations in motor
      unit recruitment strategies.

PMID- 24582370
TI  - A measure of acoustic noise generated from transcranial magnetic stimulation
      coils.
AB  - The intensity of sound emanating from the discharge of magnetic coils used in
      repetitive transcranial magnetic stimulation (rTMS) can potentially cause
      acoustic trauma. Per Occupational Safety and Health Administration (OSHA)
      standards for safety of noise exposure, hearing protection is recommended beyond
      restricted levels of noise and time limits. We measured the sound pressure levels
      (SPLs) from four rTMS coils with the goal of assessing if the acoustic artifact
      levels are of sufficient amplitude to warrant protection from acoustic trauma per
      OSHA standards. We studied the SPLs at two frequencies (5 and 10 Hz), three
      machine outputs (MO) (60, 80 and 100%), and two distances from the coil (5 and 10
      cm). We found that the SPLs were louder at closer proximity from the coil and
      directly dependent on the MO. We also found that in all studied conditions, SPLs
      were lower than the OSHA permissible thresholds for short (<15 min) acoustic
      exposure, but at extremes of use, may generate sufficient noise to warrant ear
      protection with prolonged (>8 h) exposure. 

PMID- 24582371
TI  - Transcranial direct current stimulation of the cerebellum in essential tremor: a
      controlled study.

PMID- 24582372
TI  - Targeting chronic recurrent low back pain from the top-down and the bottom-up: a
      combined transcranial direct current stimulation and peripheral electrical
      stimulation intervention.
AB  - BACKGROUND: Mechanisms such as neural sensitization and maladaptive cortical
      organization provide novel targets for therapy in chronic recurrent low back pain
      (CLBP). OBJECTIVE: We investigated the effect of a transcranial direct current
      stimulation (tDCS) and peripheral electrical stimulation (PES) treatment on pain,
      cortical organization, sensitization and sensory function in CLBP. METHODS: Using
      a placebo-controlled crossover design, 16 individuals received four treatments in
      separate sessions: (i) anodal tDCS/PES; (ii) anodal tDCS/sham PES; (iii) sham
      tDCS/PES; or (iv) sham tDCS/sham PES. Pain was assessed at baseline, immediately
      following, and at 1 and 3 days after treatment. Motor cortical organization,
      sensitization and sensory function were measured before and immediately after
      treatment. RESULTS: Combined tDCS/PES reduced pain and sensitization, normalized
      motor cortical organization and improved sensory function. The reduction in pain
      was greater in individuals with more pronounced sensitization. Applied alone,
      tDCS or PES also reduced pain. However, with the exception of improved sensory
      function and reduced map volume following PES, clinical and neurophysiological
      outcomes were unaltered by tDCS or PES applied separately. No changes were
      observed following sham treatment. CONCLUSION: Our data suggest a combined
      tDCS/PES intervention more effectively improves CLBP symptoms and mechanisms of
      cortical organization and sensitization, than either intervention applied alone
      or a sham control.

PMID- 24582373
TI  - When size matters: large electrodes induce greater stimulation-related cutaneous
      discomfort than smaller electrodes at equivalent current density.
AB  - BACKGROUND: Cutaneous discomfort is typically reported during transcranial direct
      current stimulation (tDCS), restricting the current intensity and duration at
      which tDCS can be applied. It is commonly thought that current density is
      associated with the intensity of perceived cutaneous perception such that larger
      electrodes with a lower current density results in milder cutaneous sensations.
      OBJECTIVE: The present study examined the relationship between current density,
      current intensity and cutaneous sensations perceived during tDCS. METHODS: Two
      experiments were performed. In the first control experiment, the cutaneous
      sensations induced by varying current intensities (0.025, 0.5, 1.0 and 1.5 mA)
      were examined up to 10 min. These data were used for optimizing inter-stimulation
      intervals in the second main experiment, where participants rated the intensity,
      spatial size and location of the cutaneous sensations experienced during tDCS
      using two electrodes sizes (16 cm2 and 35 cm2). In the equivalent current density
      condition, the current density was kept constant under both electrodes (0.014,
      0.029 and 0.043 mA/cm2), whereas in the equal current intensity condition (0.5,
      1.0 and 1.5 mA) the same intensities were used for the two electrode sizes.
      RESULTS: Large electrodes were associated with greater cutaneous discomfort when
      compared to smaller electrodes at a given current density. Further, levels of
      cutaneous perception were similar for small and large electrodes when current
      intensity was kept constant. CONCLUSION: Cutaneous sensations during stimulation
      can be minimized by reducing the electrode size from 35 cm2 to 16 cm2.

PMID- 24582374
TI  - Luteotrophic effect of ovulation-inducing factor/nerve growth factor present in
      the seminal plasma of llamas.
AB  - The hypothesis that ovulation-inducing factor/nerve growth factor (OIF/NGF)
      isolated from llama seminal plasma exerts a luteotrophic effect was tested by
      examining changes in circulating concentrations of LH and progesterone, and the
      vascular perfusion of the ovulatory follicle and developing CL. Female llamas
      with a growing follicle of 8 mm or greater in diameter were assigned randomly to
      one of three groups (n = 10 llamas per group) and given a single intramuscular
      dose of PBS (1 mL), GnRH (50 MUg), or purified OIF/NGF (1.0 mg). Cineloops of
      ultrasonographic images of the ovary containing the dominant follicle were
      recorded in brightness and power Doppler modalities. Llamas were examined every 4
      hours from the day of treatment (Day 0) until ovulation, and every other day
      thereafter to Day 16. Still frames were extracted from cineloops for computer
      assisted analysis of the vascular area of the preovulatory follicle from
      treatment to ovulation and of the growing and regressing phases of subsequent CL
      development. Blood samples were collected for the measurement of plasma LH and
      progesterone concentrations. The diameter of the dominant follicle at the time of
      treatment did not differ among groups (P = 0.48). No ovulations were detected in
      the PBS group but were detected in all llamas given GnRH or OIF/NGF (0/10, 10/10,
      and 10/10, respectively; P < 0.0001). No difference was detected between the GnRH
      and OIF/NGF groups in the interval from treatment to ovulation (32.0 +/- 1.9 and
      30.4 +/- 5.7 hours, respectively; P = 0.41) or in maximum CL diameter (13.1 +/-
      0.4 and 13.5 +/- 0.3 mm, respectively; P = 0.44). The preovulatory follicle of
      llamas treated with OIF/NGF had a greater vascular area at 4 hours after
      treatment than that of the GnRH group (P < 0.001). Similarly, the luteal tissue
      of llamas treated with purified OIF/NGF had a greater vascular area than that of
      the GnRH group on Day 6 after treatment (P < 0.001). The preovulatory surge in
      plasma LH concentration began, and peaked 1 to 2 hours later in the OIF/NGF group
      than in the GnRH group (P < 0.05). Plasma progesterone concentration was higher
      on Day 6 in the OIF/NGF group than in the GnRH group (P < 0.001). Results support
      the hypothesis that OIF/NGF exerts a luteotrophic effect by altering the
      secretion pattern of LH and enhancing tissue vascularization during the
      periovulatory period and early stages of CL development.

PMID- 24582375
TI  - Effect of bovine blastocyst size at embryo transfer on day 7 on conceptus length
      on day 14: can supplementary progesterone rescue small embryos?
AB  - Conceptus size on Day 14 after multiple embryo transfer of Day 7 in vitro
      produced blastocysts varies greatly within animal. One explanation for this
      variation may be related to blastocyst cell number at the time of transfer. The
      aim of this study was to examine the effect of Day 7 blastocyst cell number on
      Day 14 conceptus size and to examine the effect of progesterone (P4)
      supplementation on embryo development after the transfer of Day 7 blastocysts
      containing a low total cell number. The estrous cycles of crossbred beef heifers
      were synchronized using an 8-day progesterone (P4)-releasing intravaginal device
      (PRID) with the administration of a prostaglandin F2alpha analog on the day
      before device removal. Only those heifers recorded in standing estrus (Day 0)
      were used. Heifers were randomly assigned to one of four treatment groups: (1)
      control: large blastocysts (high total cell number), (2) control: small
      blastocysts (low total cell number), (3) small blastocysts plus a single
      intramuscular injection of 3000 IU human chorionic gonadotropin (hCG) on Day 2
      after estrus, or (4) small blastocysts plus insertion of a vaginal P4 insert
      (PRID, 1.55 g P4) between Days 3 and 5 after estrus. In vitro-produced
      blastocysts were transferred to each heifer on Day 7 (n = 10 blastocysts per
      heifer), and conceptuses were recovered at slaughter on Day 14. Daily blood
      samples were collected from Day 0 to 14 to measure serum P4 concentrations. Data
      were analyzed using the PROC MIXED procedure of SAS. Total cell number on Day 7
      was significantly lower in small versus large blastocysts (72.4 +/- 3.93 vs.
      144.8 +/- 3.90, P < 0.05). Conceptus recovery rate was 53.8% overall (140 of 260)
      and was highest in the large blastocyst group (68.3%, 41 of 60) compared with the
      other groups (45.7%-55.0%). Concentrations of serum P4 were similar in the two
      unmanipulated recipient groups but were significantly elevated (P < 0.05) by Day
      8 in the hCG-treated heifers and on Days 4 and 5 in the PRID group (P < 0.003).
      In the absence of supplemental P4, Day 14 conceptuses resulting from the transfer
      of small blastocysts (2.48 +/- 0.54 mm) were smaller than those from large
      blastocysts (3.32 +/- 0.52 mm). Administration of hCG on Day 2 approximately
      doubled conceptus length on Day 14 (4.94 +/- 1.15 mm; P < 0.05), whereas
      insertion of a PRID from Days 3 to 5 increased conceptus length approximately
      fivefold (13.09 +/- 2.11 mm; P < 0.05) compared with controls. In conclusion,
      results indicate that supplemental P4 is capable of "rescuing" poor-quality
      blastocysts, presumably via the now well-described actions on the endometrium and
      consequent effects on uterine lumen fluid composition.

PMID- 24582376
TI  - Sperm yield after single layer centrifugation with Androcoll-E is related to the
      potential fertility of the original ejaculate.
AB  - Many attempts have been made to identify laboratory tests that are predictive of
      sperm fertility, both to improve the quality of stallion semen doses for
      artificial insemination (AI) and to identify potential breeding sires if no
      fertility data are available. Sperm quality at the stud is mostly evaluated by
      assessing subjective motility, although this parameter can be poorly indicative
      of fertility. Sperm morphology and chromatin integrity in Swedish stallions are
      correlated to pregnancy rate after AI. Because single layer centrifugation (SLC)
      selects for spermatozoa with normal morphology and good chromatin, retrospective
      analysis was carried out to investigate whether sperm yield after SLC is linked
      to potential fertility. Commercial semen doses for AI from 24 stallions (five
      stallions with four ejaculates each, 19 stallions with three ejaculates each; n =
      77) obtained during the breeding season were cooled, and sent overnight to the
      Swedish University of Agricultural Sciences in an insulated box for evaluation,
      with other doses being sent to studs for commercial AI. On arrival at Swedish
      University of Agricultural Sciences, the semen was used for SLC and also for
      evaluation of sperm motility, membrane integrity, chromatin integrity, and
      morphology. The seasonal pregnancy rates for each stallion were available. The
      yield of progressively motile spermatozoa after SLC (calculated as a proportion
      of the initial load) was found to be highly correlated with pregnancy rate (r =
      0.75; P < 0.001). Chromatin damage was highly negatively correlated with
      pregnancy rate (r = -0.69; P < 0.001). Pregnancy rate was also correlated with
      membrane integrity (r = 0.58; P < 0.01), progressive motility (r = 0.63; P <
      0.01), and normal morphology (r = 0.45; P < 0.05). In conclusion, these
      preliminary results show that sperm yield after SLC is related to the potential
      fertility of the original ejaculate, and could be an alternative indicator of
      stallion fertility if breeding data are not available. Single layer
      centrifugation is fast (30 minutes) and does not require expensive equipment,
      whereas other assays require a flow cytometer and/or specialist skills. An
      additional option could be to transport semen doses to a laboratory for SLC if
      the stud personnel do not want to perform the procedure themselves.

PMID- 24582377
TI  - Inhibition of hypoxia-induced proliferation of pulmonary arterial smooth muscle
      cells by a mTOR siRNA-loaded cyclodextrin nanovector.
AB  - The proliferation of pulmonary arterial smooth muscle cells (PASMCs) is a key
      pathophysiological component of vascular remodeling in pulmonary arterial
      hypertension (PAH), an intractable disease, for which pharmacotherapy is limited
      and only slight improvement in survival outcomes have achieved over the past few
      decades. RNA interference provides a highly promising strategy to the treatment
      of this chronic lung disease, while efficient delivery of small interfering RNA
      (siRNA) remains a key challenge for the development of clinically acceptable
      siRNA therapeutics. With the aim to construct useful nanomedicines, the mammalian
      target of rapamycin (mTOR) siRNA was loaded into hybrid nanoparticles based on
      low molecular weight (Mw) polyethylenimine (PEI) and a pH-responsive cyclodextrin
      material (Ac-aCD) or poly(lactic-co-glycolic acid) (PLGA). This hybrid
      nanoplatform gave rise to desirable siRNA loading, and the payload release could
      be modulated by the hydrolysis characteristics of carrier materials. Fluorescence
      observation and flow cytometry quantification suggested that both Ac-aCD and PLGA
      nanovectors (NVs) may enter PASMCs under either normoxia or hypoxia conditions as
      well as in the presence of serum, with uptake and transfection efficiency
      significantly higher than those of cationic vectors such as PEI with Mw of 25 kDa
      (PEI25k) and Lipofectamine 2000 (Lipo 2k). Hybrid Ac-aCD or PLGA NV containing
      siRNA remarkably inhibited proliferation and activated apoptosis of hypoxic
      PASMCs, largely resulting from effective suppression of mTOR signaling as
      evidenced by significantly lowered expression of mTOR mRNA and phosphorylated
      protein. Moreover, these hybrid nanomedicines were more effective than commonly
      used cationic vectors like PEI25k and Lipo 2k, with respect to cell growth
      inhibition, apoptosis activation, and expression attenuation of mTOR mRNA and
      protein. Therefore, mTOR siRNA nanomedicines based on hybrid Ac-aCD or PLGA NV
      may be promising therapeutics for diseases related to hypoxic abnormal growth of
      PASMCs. 

PMID- 24582378
TI  - Scaffolds from block polyurethanes based on poly(E-caprolactone) (PCL) and
      poly(ethylene glycol) (PEG) for peripheral nerve regeneration.
AB  - Nerve guide scaffolds from block polyurethanes without any additional growth
      factors or protein were prepared using a particle leaching method. The scaffolds
      of block polyurethanes (abbreviated as PUCL-ran-EG) based on poly(E-caprolactone)
      (PCL-diol) and poly(ethylene glycol) (PEG) possess highly surface-area porous for
      cell attachment, and can provide biochemical and topographic cues to enhance
      tissue regeneration. The nerve guide scaffolds have pore size 1-5 MUm and
      porosity 88%. Mechanical tests showed that the polyurethane nerve guide scaffolds
      have maximum loads of 4.98 +/- 0.35 N and maximum stresses of 6.372 +/- 0.5 MPa.
      The histocompatibility efficacy of these nerve guide scaffolds was tested in a
      rat model for peripheral nerve injury treatment. Four types of guides including
      PUCL-ran-EG scaffolds, autograft, PCL scaffolds and silicone tubes were compared
      in the rat model. After 14 weeks, bridging of a 10 mm defect gap by the
      regenerated nerve was observed in all rats. The nerve regeneration was
      systematically characterized by sciatic function index (SFI), histological
      assessment including HE staining, immunohistochemistry, ammonia silver staining,
      Masson's trichrome staining and TEM observation. Results revealed that
      polyurethane nerve guide scaffolds exhibit much better regeneration behavior than
      PCL, silicone tube groups and comparable to autograft. Electrophysiological
      recovery was also seen in 36%, 76%, and 87% of rats in the PCL, PUCL-ran-EG, and
      autograft groups respectively, whilst 29.8% was observed in the silicone tube
      groups. Biodegradation in vitro and in vivo show proper degradation of the PUCL
      ran-EG nerve guide scaffolds. This study has demonstrated that without further
      modification, plain PUCL-ran-EG nerve guide scaffolds can help peripheral nerve
      regeneration excellently. 

PMID- 24582379
TI  - Thrombus age, clinical presentation, and reperfusion grade in myocardial
      infarction.
AB  - INTRODUCTION: Autopsy studies show that dynamic coronary thrombosis leads to
      infarction. We studied intracoronary thrombus age in ST-segment elevation
      myocardial infarction (STEMI) and its relationship with clinical presentation and
      epicardial reperfusion grade. METHODS AND RESULTS: Intracoronary thrombectomy was
      performed in 131 STEMI patients within 24 h after symptom onset, and material
      sufficient for pathological analysis was retrieved from 81 patients. Thrombus age
      was classified as fresh (<1day), lytic (1 to 5 days), or organized (>5days). A
      fresh thrombus was found in 48 patients (60%), whereas the thrombus showed lytic
      or organized changes in 33 patients (40%). Both thrombus and plaque material were
      aspirated in 40% of cases. Lytic or organized thrombi were aspirated in one third
      of the cases early (<12h) after symptom onset, and fresh thrombi were also
      aspirated in one third of STEMI of>12h evolution. In multivariable analysis,
      fresh thrombus was associated with both persistent ST-segment elevation (even
      after 12 h of onset) during percutaneous coronary intervention [odds ratio (OR)
      4.23, 95% confidence interval (CI) 1.05-17.42, P=.042) and a previous history of
      ischemic heart disease (OR 4.54, 95% CI 1.41-14.64, P=.011). There were no
      associations between thrombus composition and epicardial reperfusion grade or the
      presence of the no-reflow phenomenon. Plaque components were found in all cases
      of distal embolization (5%). CONCLUSION: Intracoronary thrombi aspirated in STEMI
      frequently show more than one stage of maturation. Fresh thrombi predominate in
      patients with known ischemic heart disease or persistent ST-segment elevation.
      SUMMARY: In STEMI, thromboaspiration revealed thrombi at different stages of
      maturation, supporting a dynamic process of rupture and repair of the
      atherosclerotic plaque. Fresh thrombi were present more frequently within 12 h of
      infarction onset but also in patients with symptoms beyond 12 h. When containing
      plaque material, thrombi were often associated with macroscopic distal
      embolization during angioplasty.

PMID- 24582380
TI  - Clear rhetoric and blurred reality: the development of a recovery focus in UK
      drug treatment policy and practice.
AB  - This paper looks at the transformation of UK drug treatment policy in the
      priority that is now being given to recovery. The paper explores the factors that
      helped shape that transformation and notes that in the main the influences were
      external to those directly involved in delivering drug treatment (research,
      politicians, media, think tanks) and that whilst the combined influence of these
      elements succeeded in reframing policy, it has left the realm of drug treatment
      service delivery unclear in a number of key areas including: determining how long
      drug users should remain in treatment; avoiding relapse; relations between
      professional drug workers and peer supporters; and meeting the diverse needs of
      drug users including those who are not seeking to become drug free. The paper
      concludes by considering what kind of initiatives and mechanisms may be needed to
      ensure a closer alignment between policy and practice within the drug treatment
      sphere. 

PMID- 24582381
TI  - The role of evidence and the expert in contemporary processes of governance: the
      case of opioid substitution treatment policy in England.
AB  - BACKGROUND: This paper is based on research examining stakeholder involvement in
      substitution treatment policy which was undertaken as part of the EU funded FP7
      ALICE-RAP (Addictions and Lifestyles in Contemporary Europe - Reframing
      Addictions Project). In England, the research coincided with a policy shift
      towards a recovery orientated drug treatment framework and a heated debate
      surrounding the role of substitute prescribing. The study aimed to explore the
      various influences on the development of the new 'recovery' policy from the
      perspectives of the key stakeholders involved. METHODS: The paper is based on
      documentary analyses and key informant interviews with a range of stakeholders,
      including representatives of user organisations, treatment providers, civil
      servants, and members of expert committees. RESULTS: Drawing on the theoretical
      insights offered by Backstrand's 'civic science' framework, the changing role of
      evidence and the position of experts in the processes of drugs policy governance
      are explored. 'Evidence' was used to problematise the issue of substitution
      treatment and employed to legitimise, justify and construct arguments around the
      possible directions of policy and practice. Conflicting beliefs about drug
      treatment and about motivation for policy change emerge in the argumentation,
      illustrating tensions in the governance of drug treatment and the power
      differentials separating different groups of stakeholders. Their role in the
      production of evidence also illustrates issues of power regarding the definition
      and development of 'usable knowledge'. There were various attempts at greater
      representation of different forms of evidence and participation by a wider group
      of stakeholders in the debates surrounding substitution treatment. However, key
      national and international experts and the appointment of specialist committees
      continued to play dominant roles in building consensus and translating scientific
      evidence into policy discourse. CONCLUSION: Substitution treatment policy has
      witnessed a challenge to the dominance of 'scientific evidence' within policy
      decision making, but in the absence of alternative evidence with an acceptable
      credibility and legitimacy base, traditional notions of what constitutes evidence
      based policy persist and there is a continuing lack of recognition of 'civic
      science'.

PMID- 24582382
TI  - Clinical and ultrasonographic evidence of a proximal positional fault of the
      radius. A case report.
AB  - Positional faults are considered a possible underlying mechanism mimicking the
      symptoms of a joint sprain. Despite numerous clinical studies indicating the
      presence of positional faults, there is limited evidence of imaging studies
      confirming positional faults. This case report is a preliminary study that offers
      clinical and ultrasonographic evidence of a proximal positional fault of the
      radius, treated successfully with manual therapy techniques. Three weeks after a
      bike fall on the outstretched hand, the patient in this study presented with
      right wrist pain and a lack of progress with conventional conservative treatment
      (NSAIDs, rest and immobilization). Clinical findings indicating a proximal
      positional fault of the radius included pain during active pronation increased by
      associating a passive movement of the radius in a proximal direction and it was
      reduced by associating a passive movement of the radius in a distal direction.
      Ultrasonographic (US) images showed a reduction of radio-capitellar distance on
      the right side (11.4 mm) compared to the left side (13.3 mm). A positive response
      with a distal mobilization of the radius supported the proximal positional fault
      of the radius. After two manual therapy sessions, the patient had recovered
      normal asymptomatic function. The outcomes used to assess function and pain were
      active pronation range of motion, the Spanish version of the DASH questionnaire
      and a 0-10 numeric pain rating scale. Each measure was conducted prior and after
      each treatment session and one week post treatment. The patient was re-examined
      at 6 months follow-up, during which US images, demonstrated a normalization of
      the right radio-capitellar distance.

PMID- 24582383
TI  - Age dependent electroencephalographic changes in attention-deficit/hyperactivity
      disorder (ADHD).
AB  - OBJECTIVE: Objective biomarkers for attention-deficit/hyperactivity disorder
      (ADHD) could improve diagnostics or treatment monitoring of this psychiatric
      disorder. The resting electroencephalogram (EEG) provides non-invasive spectral
      markers of brain function and development. Their accuracy as ADHD markers is
      increasingly questioned but may improve with pattern classification. METHODS:
      This study provides an integrated analysis of ADHD and developmental effects in
      children and adults using regression analysis and support vector machine
      classification of spectral resting (eyes-closed) EEG biomarkers in order to
      clarify their diagnostic value. RESULTS: ADHD effects on EEG strongly depend on
      age and frequency. We observed typical non-linear developmental decreases in
      delta and theta power for both ADHD and control groups. However, for ADHD adults
      we found a slowing in alpha frequency combined with a higher power in alpha-1 (8
      10Hz) and beta (13-30Hz). Support vector machine classification of ADHD adults
      versus controls yielded a notable cross validated sensitivity of 67% and
      specificity of 83% using power and central frequency from all frequency bands.
      ADHD children were not classified convincingly with these markers. CONCLUSIONS:
      Resting state electrophysiology is altered in ADHD, and these
      electrophysiological impairments persist into adulthood. SIGNIFICANCE: Spectral
      biomarkers may have both diagnostic and prognostic value.

PMID- 24582384
TI  - Assessment of lingual nerve injury using different surgical variables for
      mandibular third molar surgery: a clinical study.
AB  - The objective of this study was to investigate the incidence of sensory
      impairment of the lingual nerves following lower third molar removal and to
      compare the outcome with various operative variables. A total of 1200 mandibular
      third molars were removed under local anaesthesia. Predictor variables were
      categorized as lingual flap retraction, tooth sectioning, and buccal guttering.
      The outcome variable was the presence or absence of lingual nerve impairment.
      Different operative techniques were performed to identify independent predictors.
      Of the 1200 patients, 67 (5.6%) experienced transient sensory impairment at the 1
      week follow-up. In all cases this resolved completely during the study period,
      except for four (0.3%) patients who suffered permanent impairment of lingual
      nerve function. Factors that predicted lingual nerve injury were lingual flap
      retraction, tooth sectioning, and buccal guttering. The incidence of lingual
      nerve injury was greater when combinations of these operative variables were
      used. 

PMID- 24582385
TI  - Small area associations between social context and alcohol-attributable mortality
      in a middle income country.
AB  - BACKGROUND: Little is known about the association between alcohol-attributable
      mortality and small area socioeconomic variables when considering causes both
      wholly and partially attributable to alcohol. METHODS: An ecological study was
      conducted of the entire Chilean population aged 15 and older in 345
      municipalities nationwide between 2004 and 2009. Deaths were attributed to
      alcohol consumption either wholly or partially, along with the estimated
      attributable fractions for each specified cause. Each municipality was
      characterized according to its average income and educational attainment.
      Estimates of the ecological associations were produced using a hierarchical
      Bayesian model, separating out deaths caused by alcohol and dividing them into
      seven groups of causes. RESULTS: Alcohol-attributable mortality risk showed an
      inverse association with income and education at the ecological level. A one
      quintile increase in income was associated with an average decrease in risk of
      10% (CI 95%: 10-20%) for cardiovascular deaths, 8% (6-10%) for intentional
      injuries and 7% (3-11%) for unintentional injuries. No associations were found
      between deaths due to cancers and other causes with income and education.
      CONCLUSIONS: Municipalities with lower income and education have higher risk of
      alcohol-attributable mortality in Chile.

PMID- 24582387
TI  - Inhibition of diacylglycerol kinases as a physiological way to promote
      diacylglycerol signaling.
AB  - Diacylglycerol is a key regulator of cell physiology, controlling the membrane
      recruitment and activation of signaling molecules. Accordingly, diacylglycerol
      generation and metabolism are strictly controlled, allowing for localized
      regulation of its concentration. While the increased production of diacylglycerol
      upon receptor triggering is well recognized, the modulation of diacylglycerol
      metabolism by diacylglycerol kinases (DGKs) is less characterized. Some agonists
      induce DGK activation and recruitment to the plasma membrane, promoting
      diacylglycerol metabolism to phosphatidic acid. Conversely, several reports
      indicate that signaling pathways that selectively inhibits DGK isoforms can
      enhance cellular diacylglycerol levels and signal transduction. For example, the
      impairment of DGKtheta activity by RhoA binding to the catalytic domain
      represents a conserved mechanism controlling diacylglycerol signaling from
      Caenorhabditis elegans motoneurons to mammalian hepatocytes. Similarly, DGKalpha
      activity is inhibited in lymphocytes by TCR signaling, thus contributing to a
      rise in diacylglycerol concentration for downstream signaling. Finally, DGKMU
      activity is inhibited by ischemia-reperfusion-generated reactive oxygen species
      in airway endothelial cells, promoting diacylglycerol-mediated ion channel
      opening and edema. In those systems, DGKs provide a gatekeeper function by
      blunting diacylglycerol levels or possibly establishing permissive domains for
      diacylglycerol signaling. In this review, I discuss the possible general
      relevance of DGK inhibition to enhanced diacylglycerol signaling. 

PMID- 24582386
TI  - Is atherosclerosis fundamental to human aging? Lessons from ancient mummies.
AB  - Case reports from Johan Czermak, Marc Ruffer, and others a century or more ago
      demonstrated ancient Egyptians had atherosclerosis three millennia ago. The Horus
      study team extended their findings, demonstrating that atherosclerosis was
      prevalent among 76 ancient Egyptian mummies and among 61 mummies from each of the
      ancient cultures of Peru, the American Southwest, and the Aleutian Islands. These
      findings challenge the assumption that atherosclerosis is a modern disease caused
      by present day risk factors. An extensive autopsy of an ancient Egyptian teenage
      male weaver named Nakht found that he was infected with four parasites:
      Schistosoma haematobium, Taenia species, Trichinella spiralis, and Plasmodium
      falciparum. Modern day patients with chronic inflammatory disease such as
      rheumatoid arthritis, systemic lupus erythematosus, and human immunodeficiency
      virus experience premature atherosclerosis. Could the burden of chronic
      inflammatory disease have been a risk factor for atherosclerosis in these ancient
      cultures? The prevalence of atherosclerosis in four diverse ancient cultures is
      consistent with atherosclerosis being fundamental to aging. The impact of risk
      factors in modern times, and potentially in ancient times, suggests a strong gene
      environmental interplay: human genes provide a vulnerability to atherosclerosis,
      the environment determines when and if atherosclerosis becomes manifest
      clinically.

PMID- 24582388
TI  - Thermal hydrolysis integration in the anaerobic digestion process of different
      solid wastes: energy and economic feasibility study.
AB  - An economic assessment of thermal hydrolysis as a pretreatment to anaerobic
      digestion has been achieved to evaluate its implementation in full-scale plants.
      Six different solid wastes have been studied, among them municipal solid waste
      (MSW). Thermal hydrolysis has been tested with batch lab-scale tests, from which
      an energy and economic assessment of three scenarios is performed: with and
      without energy integration (recovering heat to produce steam in a cogeneration
      plant), finally including the digestate management costs. Thermal hydrolysis has
      lead to an increase of the methane productions (up to 50%) and kinetics
      parameters (even double). The study has determined that a proper energy
      integration design could lead to important economic savings (5 ?/t) and thermal
      hydrolysis can enhance up to 40% the incomes of the digestion plant, even
      doubling them when digestate management costs are considered. In a full-scale MSW
      treatment plant (30,000 t/year), thermal hydrolysis would provide almost 0.5
      M?/year net benefits.

PMID- 24582389
TI  - Changes in nasopharyngeal carriage of Streptococcus pneumoniae, Haemophilus
      influenzae and Moraxella catarrhalis among healthy children attending a day-care
      centre before and after official financial support for the 7-valent pneumococcal
      conjugate vaccine and H. influenzae type b vaccine in Japan.
AB  - The 7-valent pneumococcal conjugate vaccine (PCV7) and Haemophilus influenzae
      type b (Hib) vaccine reduce nasopharyngeal carriage of vaccine-type bacteria,
      which may in turn influence the presence of other nasopharyngeal bacterial
      pathogens. To investigate this possibility, nasopharyngeal carriage of potential
      pathogens was examined before and after official financial support was provided
      to offer the PCV7 and Hib vaccines in healthy children attending a day care
      centre in Japan during 2011-2012. Despite a virtual disappearance of PCV7
      serotypes over time, the overall pneumococcal carriage rate remained unchanged.
      Although others have reported an increase in PCV13 serotypes following PCV7
      vaccination, only non-PCV13 serotypes were observed to have increased in this
      study. The majority of H. influenzae isolates were non-typeable and Hib was not
      found. Our data identified an unexpected pattern of pneumococcal serotype
      replacement following PCV7. Continuous monitoring of pneumococcal carriage is
      important for decisions regarding the future of national vaccination policy in
      Japan. 

PMID- 24582390
TI  - Nurse/family caregiver intervention for delirium increases delirium knowledge and
      improves attitudes toward partnership.
AB  - Delirium is highly prevalent, especially in hospitalized older adults and is a
      costly, significant predictor of poor outcomes, including mortality and
      institutionalization. Partnership between family caregivers and staff nurses
      could be a cost-neutral preventive strategy. The Nurse/Family Caregiver
      Partnership for Delirium Prevention (NFCPM) is an innovative educational program
      that concurrently teaches family caregivers and nurses about delirium and
      partnering in prevention. The purpose of this feasibility study was to examine
      the effect of the NFCPM on knowledge of delirium, attitudes toward partnership,
      and satisfaction with the NFCPM. A quasi-experimental pretest-posttest design was
      used to enroll 28 patients, 28 family caregivers, and 28 staff nurses. The
      intervention group significantly improved knowledge of delirium and attitudes
      toward partnership. Key to satisfaction were participation in decision making,
      communication, and respect. The NFCPM appears feasible for clinical practice and
      provides an innovative strategy for family and nurses to improve hospital
      outcomes for older adults. 

PMID- 24582391
TI  - The determination of acrylamide in environmental and drinking waters by large
      volume injection - hydrophilic-interaction liquid chromatography and tandem mass
      spectrometry.
AB  - A simple and sensitive analytical method was developed to quantify levels of
      acrylamide in environmental and drinking waters. The analytical method consisted
      of solvent exchanging acrylamide from 2mL of water into 2mL of dichloromethane
      using acetonitrile as an intermediate. The sample was then directly analyzed by
      large-volume (750MUL) injection - hydrophilic-interaction liquid chromatography
      and tandem mass spectrometry. The method detection limit and reporting level were
      2.4ng/L and 17ng/L of acrylamide, respectively. The recovery of acrylamide during
      solvent exchange was 95+/-2.8% and the matrix effects were 12+/-2.2% in river
      water. The use of atmospheric-pressure chemical ionization reduced matrix
      effects; however, it also reduced method sensitivity by a factor of 2.2 compared
      to electrospray ionization. Matrix effects were compensated for by the use of an
      isotopically-labeled internal standard and the method accuracy was 89+/-3.0% at
      25ng/L of acrylamide and 102+/-2.6% at 250ng/L of acrylamide. The precision of
      the method was less than 6% relative standard deviation at both 25ng/L and
      250ng/L of acrylamide. Samples from a sand-and-gravel mine and a drinking-water
      treatment plant were acquired to demonstrate the method. The concentrations of
      acrylamide at the sand-and-gravel mine were up to 280ng/L. In the drinking-water
      treatment plant, the concentration of acrylamide was approximately double in the
      finished drinking water when compared to other stages in the drinking-water
      treatment process. Disinfection or fluoridation may result in higher
      concentrations of acrylamide in finished drinking water; however, further
      research in this area is necessary. 

PMID- 24582392
TI  - New sorbent in the dispersive solid phase extraction step of quick, easy, cheap,
      effective, rugged, and safe for the extraction of organic contaminants in
      drinking water treatment sludge.
AB  - Recent studies have shown a decrease in the concentration of pesticides,
      pharmaceuticals and personal care products (PCPs) in water after treatment. A
      possible explanation for this phenomenon is that these compounds may adhere to
      the sludge; however, investigation of these compounds in drinking water treatment
      sludge has been scarce. The sludge generated by drinking water treatment plants
      during flocculation and decantation steps should get some special attention not
      only because it has been classified as non-inert waste but also because it is a
      very complex matrix, consisting essentially of inorganic (sand, argil and silt)
      and organic (humic substances) compounds. In the first step of this study, three
      QuEChERS methods were used, and then compared, for the extraction of pesticides
      (atrazine, simazine, clomazone and tebuconazole), pharmaceuticals (amitriptyline,
      caffeine, diclofenac and ibuprofen) and PCPs (methylparaben, propylparaben,
      triclocarban and bisphenol A) from drinking water treatment sludge. Afterwards,
      the study of different sorbents in the dispersive solid phase extraction (d-SPE)
      step was evaluated. Finally, a new QuEChERS method employing chitin, obtained
      from shrimp shell waste, was performed in the d-SPE step. After having been
      optimized, the method showed limits of quantification (LOQ) between 1 and 50 MUg
      kg(-1) and the analytical curves showed r values higher than 0.98, when liquid
      chromatography tandem mass spectrometry was employed. Recoveries ranged between
      50 and 120% with RSD<=15%. The matrix effect was evaluated and compensated with
      matrix-matched calibration. The method was applied to drinking water treatment
      sludge samples and methylparaben and tebuconazole were found in concentration
      <LOQ.

PMID- 24582393
TI  - Combining liquid chromatography with multiplexed capillary gel electrophoresis
      for offline comprehensive analysis of complex oligonucleotide samples.
AB  - Offline two dimensional liquid chromatography (LC)*capillary gel electrophoresis
      (CGE) and LC*(24) multiplexed-CGE methodologies were developed for the separation
      of oligonucleotides of therapeutic size. Both ion-pair chromatography (IPC) and
      ion-exchange chromatography (IEC) were studied as methods for the first dimension
      and single and multiplexed capillary electrophoresis methods in entangled polymer
      solutions were used for the second dimension separations. Electrokinetic and
      pressure injection were evaluated for the analysis of the collected LC fractions.
      The comprehensive separation was optimized with standard mixtures of poly
      adenosine, thymidine, cytosine and uracil homodeoxyoligonucleotides up to 35
      bases long. Highly orthogonal methodologies and overall peak capacities of 6435
      and 6993 for IPC*CGE and IEC*CGE, respectively, were obtained within a few hours
      analysis time. 

PMID- 24582394
TI  - Determination of benzotriazoles in water samples by concurrent derivatization
      dispersive liquid-liquid microextraction followed by gas chromatography-mass
      spectrometry.
AB  - Concurrent acetylation-dispersive liquid-liquid microextraction (DLLME) combined
      with gas chromatography-mass spectrometry (GC-MS) has been proposed for the
      sensitive determination of five polar benzotriazolic compounds (1H-benzotriazole,
      BTri; 4 and 5-methyl-1H-benzotriazole, 4-TTri and 5-TTri; 5,6-dimethyl-1H
      benzotriazole, XTri; and 5-chloro-1H-benzotriazole, 5-ClBTri) in water samples.
      Under optimized conditions, samples (10 mL volume) were combined with 1 mL of
      Na2HPO4 (8%, w/v) and mixed with the ternary acetylation-microextraction mixture,
      consisting of 100 MUL of acetic anhydride, 1.5 mL of acetonitrile and 60 MUL of
      toluene. Thus, analytes were simultaneously acetylated and transferred to the
      dispersed droplets of toluene. The proposed methodology achieved limits of
      quantification (LOQs) between 0.007 ng mL(-1) and 0.080 ng mL(-1), enrichment
      factors between 93 and 172 times, good reproducibility, with relative standard
      deviations lower than 10%, and linearity with determination coefficients above
      0.9991 for all compounds in the range between LOQs and 20 ng mL(-1). Pseudo
      external calibration, with fortified ultrapure water samples submitted to the
      acetylation-DLLME procedure, proved to be adequate for the accurate
      quantification of complex aqueous matrices such as surface or wastewater,
      providing recoveries comprised between 86% and 112%. BTri, 4-TTri and 5-TTri were
      measured in environmental samples up to a concentration of 1.9 ng mL(-1) for BTri
      in raw wastewater.

PMID- 24582395
TI  - Determination of selected pharmaceutical compounds in biosolids by supported
      liquid extraction and gas chromatography-tandem mass spectrometry.
AB  - In this work, an analytical method was developed for the determination of
      pharmaceutical drugs in biosolids. Samples were extracted with an acidic mixture
      of water and acetone (1:2, v/v) and supported liquid extraction was used for the
      clean-up of extracts, eluting with ethyl acetate:methanol (90:10, v/v). The
      compounds were determined by gas chromatography-tandem mass spectrometry using
      matrix-match calibration after silylation to form their t-butyldimethylsilyl
      derivatives. This method presents various advantages, such as a fairly simple
      operation for the analysis of complex matrices, the use of inexpensive glassware
      and low solvent volumes. Satisfactory mean recoveries were obtained with the
      developed method ranging from 70 to 120% with relative standard deviations (RSDs)
      <= 13%, and limits of detection between 0.5 and 3.6 ng g(-1). The method was then
      successfully applied to biosolids samples collected in Madrid and Catalonia
      (Spain). Eleven of the sixteen target compounds were detected in the studied
      samples, at levels up to 1.1 MUg g(-1) (salicylic acid). Ibuprofen, caffeine,
      paracetamol and fenofibrate were detected in all of the samples analyzed.

PMID- 24582396
TI  - Beyond dispersive liquid-liquid microextraction.
AB  - Dispersive liquid-liquid microextraction (DLLME) and other dispersion liquid
      phase microextraction (LPME) methods have been developed since the first DLLME
      method was reported in 2006. DLLME is simple, rapid, and affords high enrichment
      factor, this is due to the large contact surface area of the extraction solvent.
      DLLME is a method suitable for the extraction in many different water samples,
      but it requires using chlorinated solvents. In recent years, interest in DLLME or
      dispersion LPME has been focused on the use of low-toxicity solvents and more
      conveniently practical procedures. This review examines some of the most
      interesting developments in the past few years. In the first section, DLLME
      methods are separated in two categories: DLLME with low-density extraction
      solvent and DLLME with high-density extraction solvent. Besides these methods,
      many novel special devices for collecting low-density extraction solvent are also
      mentioned. In addition, various dispersion techniques with LPME, including manual
      shaking, air-assisted LPME (aspirating and injecting the extraction mixture by
      syringe), ultrasound-assisted emulsification, vortex-assisted emulsification,
      surfactant-assisted emulsification, and microwave-assisted emulsification are
      described. Besides the above methods, combinations of DLLME with other extraction
      techniques (solid-phase extraction, stir bar sorptive extraction, molecularly
      imprinted matrix solid-phase dispersion and supercritical fluid extraction) are
      introduced. The combination of nanotechnique with DLLME is also introduced.
      Furthermore, this review illustrates the application of DLLME or dispersion LPME
      methods to separate and preconcentrate various organic analytes, inorganic
      analytes, and samples. 

PMID- 24582397
TI  - Evaluation of the oxidative deoxyribonucleic acid damage biomarker 8-hydroxy-2'
      deoxyguanosine in the urine of leukemic children by micellar electrokinetic
      capillary chromatography.
AB  - Determining the level of urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG), an
      oxidative DNA damage biomarker, is vital to the study of clinical pathogenesis
      and drug toxicity. The principal limitation of capillary electrophoresis (CE)
      with UV detection is its low sensitivity. To overcome this shortcoming, we
      developed a micellar electrokinetic capillary chromatography (MEKC) with solid
      phase extraction (SPE) for urinary 8-OHdG analysis. The sensitivity of MEKC-UV
      was improved using a reasonable UV system, injection mode, and SPE. The
      parameters affecting MEKC and SPE were also optimized. The calibration curve was
      linear within the range from 1 to 500 MUg L(-1). The limits of detection and
      quantification were 0.27 MUg L(-1) and 0.82 MUg L(-1), respectively. Interday and
      intraday precision were both <5.6%. The recovery of 8-OHdG in urine ranged from
      94.5% to 103.2%. This method was used to measure urinary 8-OHdG from eight normal
      children, eight newly diagnosed leukemic children, and eight leukemic children
      undergoing chemotherapy. The results show that the proposed method can be used to
      assess oxidative stress in patients and the side effects of chemotherapeutic
      drugs by measuring urinary 8-OHdG.

PMID- 24582398
TI  - Ultrasound-assisted solid phase extraction of nitro- and chloro-(phenols) using
      magnetic iron oxide nanoparticles and Aliquat 336 ionic liquid.
AB  - A novel and sensitive ultrasound-assisted solid phase extraction (UASPE) method
      for pre-concentration and determination of ultra-trace amounts of nitrophenols
      and chlorophenols in water samples was demonstrated. Four hazardous phenolic
      compounds in water samples were extracted and monitored by high performance
      liquid chromatography. The results demonstrated that in the presence of Aliquat
      336 (ALQ), magnetic iron oxide nanoparticles (MIONPs) were quite efficient in the
      adsorption and pre-concentration of traces of analytes. MIONPs were synthesized
      and characterized by transmission electron microscopy (TEM) and X-ray diffraction
      (XRD). The important parameters influencing the extraction efficiency were
      studied and optimized. The separation and pre-concentration steps were fast and
      completed in 10 min. Acetonitrile was used for the desorption of target analytes.
      Under optimum adsorption conditions, a linear range between 0.015 and 100 MUg L(
      1) (R(2)>=0.997), and limits of detections (LODs) ranging from 0.005 to 0.041 MUg
      L(-1) were obtained. Enrichment factors in the range of 76-195 were achieved and
      relative standard deviations (%RSDs) were less than 10.0 (n=3) for the target
      analytes. The analytical method was successfully applied for environmental water
      samples such as tap water and river water. The recoveries varied within the range
      of 70-119% confirming the good performance of the method in various water
      samples. The results showed that the proposed method is a rapid, convenient and
      feasible technique for the determination of nitrophenols and chlorophenols in
      aqueous samples.

PMID- 24582399
TI  - [Chronic obstructive pulmonary disease and ischemic heart disease: A not so rare
      association].

PMID- 24582400
TI  - Evaluation of 1,2,5-thiadiazoles as modulators of M1/M5 muscarinic receptor
      subtypes.
AB  - Studies have demonstrated the presence of allosteric binding sites on each of the
      muscarinic acetylcholine receptor (mAChR) subtypes. Since most drugs targeting
      muscarinic receptors bind to the highly conserved orthosteric binding site, they
      fail to achieve appreciable subtype selectivity. Targeting non-conserved
      allosteric sites may provide a new way of enhancing selectivity for individual
      subtypes of muscarinic receptor. Tetra(ethyleneglycol)(3-methoxy-1,2,5-thiadiazol
      4-yl)[3-(1-methyl-1,2,5,6-tetrahydropyrid-3-yl)-1,2,5-thiadiazol-4-yl] ether, CDD
      0304 (10), was found to be a M1/2/4 selective muscarinic agonist and might prove
      useful in treating the symptoms associated with schizophrenia (J. Med. Chem.2003,
      46, 4273). It was hypothesized that the observed subtype selectivity demonstrated
      by 10 may be due to its ability to function as a bitopic ligand (J. Med.
      Chem.2006, 49, 7518). To further investigate this possibility, a novel series of
      compounds was synthesized using a 1,2,5-thiadiazole moiety along with varying
      lengths of a polyethylene glycol linker and terminal groups, for evaluation as
      potential allosteric modulators of muscarinic receptors. Preliminary biological
      studies were performed using carbachol to stimulate M1 and M5 receptors. No
      significant agonist activity was observed at either M1 or M5 receptors for any of
      the compounds. Compound 18, 2-(4-methoxy-1,2,5-thiadiazol-3-yloxy)-N,N
      dimethylethanamine fumarate (CDD-0361F) was found to block the effects of
      carbachol at M5 muscarinic receptors.

PMID- 24582401
TI  - Anti-allodynic effect of 2-(aminomethyl)adamantane-1-carboxylic acid in a rat
      model of neuropathic pain: a mechanism dependent on CaV2.2 channel inhibition.
AB  - Neuropathic pain is a serious physical disabling condition resulting from lesion
      or dysfunction of the peripheral sensory nervous system. Despite the fact that
      the mechanisms underlying neuropathic pain are poorly understood, the involvement
      of voltage-gated calcium (Ca(V)) channels in its pathophysiology has justified
      the use of drugs that bind the Ca(V) channel alpha2delta auxiliary subunit, such
      as gabapentin (GBP), to attain analgesic and anti-allodynic effects in models
      involving neuronal sensitization and nerve injury. GBP binding to alpha2delta
      inhibits nerve injury-induced trafficking of the alpha1 pore forming subunits of
      Ca(V) channels, particularly of the N-type, from the cytoplasm to the plasma
      membrane of pre-synaptic terminals in dorsal root ganglion neurons and dorsal
      horn spinal neurons. In the search for alternative forms of treatment, in this
      study we describe the synthesis and pharmacological profile of a GABA derivative,
      2-aminoadamantane-1-carboxylic acid (GZ4), which displays a close structure
      activity relationship with GBP. Behavioral assessment using von Frey filament
      stimuli showed that GZ4 treatment reverted mechanical allodynia/hyperalgesia in
      an animal model of spinal nerve ligation-induced neuropathic pain. In addition,
      using the patch clamp technique we show that GZ4 treatment significantly
      decreased whole-cell currents through N-type Ca(V) channels heterologously
      expressed in HEK-293 cells. Interestingly, the behavioral and
      electrophysiological time course of GZ4 actions reflects that its mechanism of
      action is similar but not identical to that of GBP. While GBP actions require at
      least 24 h and imply uptake of the drug, which suggests that the drug acts mainly
      intracellularly affecting channels trafficking to the plasma membrane, the faster
      time course (1-3 h) of GZ4 effects suggests also a direct inhibition of Ca(2+)
      currents acting on cell surface channels.

PMID- 24582403
TI  - Author reply: To PMID 23664471.

PMID- 24582402
TI  - Cytotoxic cardiac glycosides and coumarins from Antiaris toxicaria.
AB  - Eight new cardiac glycosides/aglycones (antiaritoxiosides A-G, 1-7, and
      antiarotoxinin B, 8), two new coumarins (anticarins A-B, 41-42), and two new
      flavanones (antiarones L-K, 43-44) were isolated from trunk bark of Antiaris
      toxicaria together with 53 known compounds. The new structures were established
      by extensive analysis of spectroscopic data. Compound 1 (10-carboxy and 3alpha
      hydroxy) and compounds 3-6 (10-hydroxy) contain unique substituents that are
      rarely found in cardiac glycosides. The cytotoxic effects of isolated compounds
      against ten human cancer cell lines, KB, KB-VIN, A549, MCF-7, U-87-MG, PC-3, 1A9,
      CAKI-1, HCT-9 and S-KMEL-2, were tested using the sulforhodamine B assay. Five
      compounds (12, 16, 20, 22, and 31) showed significant cytotoxicity against all
      ten cancer cell lines, with notable potency at the ng/mL level against some cell
      lines, which merits further development as clinical trial candidates. 

PMID- 24582404
TI  - Re: Ronnback et al.: Imaging of the macula indicates early completion of
      structural deficit in autosomal-dominant optic atrophy (Ophthalmology
      2013;120:2672-7).

PMID- 24582405
TI  - Re: Huang et al.: Ocular demodicosis as a risk factor of pterygium recurrence
      (Ophthalmology 2013;120:1341-7).

PMID- 24582406
TI  - Author reply: To PMID 24120325.

PMID- 24582407
TI  - Recurrent severe abdominal pain in the pediatric patient.
AB  - BACKGROUND: Ureteropelvic junction obstruction (UPJO) is a blockage occurring at
      the junction of the ureter and the renal pelvis. Pediatric patients with UPJO
      pose a diagnostic challenge when they present to the emergency department (ED)
      with severe recurrent abdominal pain if there is not a level of suspicion for
      this condition. OBJECTIVES: Our aim was to review presentation of UPJO to the ED,
      methods of diagnosis, and treatment of this common but often overlooked
      condition. CASE REPORT: We report on 2 patients, a 9-year-old and 3-year-old, who
      had multiple presentations to health care providers and the ED with intermittent
      and recurrent abdominal pain. Subsequent testing, including ultrasound (US) and
      computed tomography (CT) with diuretic-recreated symptoms, revealed UPJO. Open
      pyeloplasty was performed, resulting in complete resolution of symptoms.
      CONCLUSIONS: UPJO is an important diagnosis to consider when patients present to
      the ED with recurrent abdominal pain. US can be helpful in suspecting the
      diagnosis, but often CT, magnetic resonance urography, or diuretic scintigraphy
      is required for confirmation. Diuretics can be used to aid diagnostic testing by
      reproducing abdominal pain at the time of imaging. Referral to a urologist for
      open pyeloplasty is definitive treatment for this condition.

PMID- 24582408
TI  - Effects of garments on photoanthropometry of body parts: application to stature
      estimation.
AB  - Person identification from images is an important task in many security
      applications and forensic investigations. The essence of the problem comes down
      to measuring key observable anatomical features which can help describing
      similarities or differences between two or more individuals. In this paper, we
      examine how different types of garments affect the placement of body markers that
      enable precise anatomical human description. We focus in particular on landmark
      positioning errors on the upper limb. Closed-form formulae are provided to
      compute the maximum likelihood estimate of upper limb length from an image.
      Subject stature is then predicted from the limb length through a regression model
      and used as identification criterion. Following initial laboratory experiments,
      the technique is demonstrated to be invariant to posture and applicable to
      uninformed subjects in unconstrained environments. Seven technical errors of
      measurement and statistical tests are quantified empirically from statures
      obtained by three assessors. Results show that thicker garments produce higher
      inaccuracies in landmark localisation but errors decrease as placement is
      repeated, as expected. Overall, comparison to truth reveals that on average
      statures are predicted with accuracy in excess of 96% for the worst assessor. 

PMID- 24582409
TI  - [Pseudotumoral abdominal nocardiosis: an uncommon clinical presentation].

PMID- 24582410
TI  - [Intravenous ferric carboxymaltose for the treatment of anemia in chronic renal
      disease].

PMID- 24582411
TI  - Anemia, iron and vitamin B12 deficiencies after sleeve gastrectomy compared to
      Roux-en-Y gastric bypass: a meta-analysis.
AB  - BACKGROUND: The effective treatment of postoperative anemia and nutritional
      deficiencies is critical for the successful management of bariatric patients.
      However, the evidence for nutritional risk or support of bariatric patients
      remains scarce. The aims of this study were to assess current evidence of the
      association between 2 methods of bariatric surgery, sleeve gastrectomy (SG) and
      Roux-en-Y gastric bypass (RYGB), and postoperative anemia and nutritional
      deficiencies. METHODS: MEDLINE, EMBASE, and the Cochrane Central Register of
      Controlled Trials were searched for English-language studies using a list of
      keywords. Reference lists from relevant review articles were also searched. In
      the authors' meta-analysis, they included studies with a duration of>12 months,
      those comparing SG with RYGB, and those with available outcome data for
      postoperative anemia and iron and vitamin B12 deficiencies. Of 36 potentially
      relevant studies, 9 met the inclusion criteria. Data were combined by means of a
      fixed-effects model or random-effects model. RESULTS: Compared with the SG group,
      the odds ratio for postoperative vitamin B12 deficiency in the RYGB group was
      3.55 (95% confidence interval, 1.26-10.01; P<.001). In the subgroup analysis,
      studies in which prophylactic iron or vitamin B12 was administered lost
      significance in the odds ratio for postoperative vitamin B12 deficiency.
      CONCLUSION: The authors' findings suggest that SG is more beneficial than RYGB
      with regard to postoperative vitamin B12 deficiency risk, whereas the 2 methods
      are comparable with regard to the risk of postoperative anemia and iron
      deficiency. Postoperative prophylactic iron and B12 supplementation, in addition
      to general multivitamin and mineral supplementation, is recommended based on the
      comparable deficiency risk of the 2 methods as indicated by subgroup analysis.

PMID- 24582412
TI  - Comment on: Long-term multiple intragastric balloon treatment-a new strategy to
      treat morbid obese patients refusing surgery: prospective 6-year follow-up study.

PMID- 24582413
TI  - A systematic review of gastric plication for the treatment of obesity.
AB  - BACKGROUND: Laparoscopic gastric plication (LGP) is a relatively new restrictive
      bariatric procedure that requires no gastrectomy or foreign body placement.
      OBJECTIVES: The authors' aim in this article is to conduct a systematic review of
      the currently available literature regarding the outcomes of LGP for the
      treatment of obesity. SETTING: University Hospital, China METHODS: The authors'
      systematic review yielded 14 studies encompassing 1,450 LGP patients.
      Perioperative data were collected from each study and recorded. RESULTS: Mean
      preoperative body mass index (BMI) ranged from 31.2 to 44.5 kg/m(2), and 80.8% of
      the patients were female. Operative time ranged from 50 to 117.9 minutes (average
      79.2 min). Hospital stay varied from .75 to 5 days (average 2.4 days). The
      percentage of excessive weight loss (%EWL) for LGP varied from 31.8% to 74.4%
      with follow-up from 6 months to 24 months. No mortality was reported in these
      studies and the rate of major complications requiring reoperation ranged from 0%
      to 15.4% (average 3.7 %). CONCLUSION: Early reports with LGP are promising with a
      favorable short-term safety profile. However, it remains unclear if weight loss
      following LGP is durable in the long term. Additional prospective comparative
      trials and long-term follow-up are needed to further define the role of LGP in
      the surgical management of obesity.

PMID- 24582414
TI  - Safety and efficacy of laparoscopic adjustable gastric banding in patients aged
      seventy and older.
AB  - BACKGROUND: Life expectancy is increasing, with more elderly people categorized
      as obese. The objective of this study was to assess the effects of laparoscopic
      adjustable gastric banding (LAGB) on patients aged >= 70 years. METHODS: This was
      a retrospective analysis of patients aged >= 70 years who underwent LAGB at our
      university hospital between 2003 and 2011. The data included age, weight, body
      mass index (BMI), and percentage excess weight loss (%EWL) obtained before and
      after gastric banding. Operative data, length of stay, postoperative
      complications, and resolution of co-morbid conditions were also analyzed.
      RESULTS: Fifty-five patients aged >= 70 years (mean 73 years) underwent gastric
      banding between 2003 and 2012. Mean preoperative weight and BMI were 123
      kilograms and 45 kg/m(2), respectively. On average, each patient had 4 co
      morbidities preoperatively, with hypertension (n = 49; 86%), dyslipidemia (n =
      40; 70%), and sleep apnea (n = 31; 54%) being the most common. Mean operating
      room (OR) time was 49 minutes, with all patients discharged within 24 hours.
      There was 1 death at 4 years from myocardial infarction, no intensive care unit
      admissions, and no 30-day readmissions. Mean %EWL at 1, 2, 3, 4, and 5 years was
      36 (+/- 12.7), 40 (+/- 16.4), 42 (+/- 19.2), 41 (+/- 17.1), 50 (+/- 14.9), and 48
      (+/- 22.6), respectively. Follow-up rates ranged from 55/55 (100%) at 6 months to
      7/9 (78%) of eligible patients at 5 years and 2/2 (100%) at 8 years.
      Complications included 1 band slip at year 5, 1 band removed for intolerance, and
      1 port site hernia. The resolution of hypertension, dyslipidemia, sleep apnea,
      lower back pain, and non-insulin-dependent diabetes was 27%, 28%, 35%, 31%, and
      35%, respectively. CONCLUSIONS: LAGB as a primary treatment for obesity in
      carefully selected patients aged >= 70 can be well tolerated and effective with
      moderate resolution of co-morbid conditions and few complications.

PMID- 24582415
TI  - Hypertension remission 1 year after bariatric surgery: predictive factors.
AB  - BACKGROUND: There is scarce information about predictive factors of hypertension
      (HT) remission after bariatric surgery (BS). The aims of this study were to
      determine the clinical characteristics differentiating obese patients with and
      without HT and to evaluate the predictive factors associated with the risk of
      persistence of HT after BS. PATIENTS AND METHODS: From January 2007 to December
      2009, a review of patients who had undergone BS was performed. Patients were
      classified as hypertensive if having permanent use of antiHT drugs or clinical BP
      >= 140/90 mm Hg. Weight, waist circumference (WC), and blood pressure were
      determined with standardized procedures. RESULTS: Five hundred twenty-6 patients
      met the inclusion criteria; 264 (50%) were hypertensive, 74 (34%) of whom had
      type 2 diabetes. Before BS, older age, male gender, and greater WC differentiated
      hypertensive from normotensive patients. The prevalence of HT significantly fell
      to 35% (P<.0001) at 12 months after BS. The use of multivariate logistic
      regression showed that age >= 40, male gender and WC >= 130 cm were significant
      predictors of having HT before surgery. Regarding persistence of HT at the 12
      month follow-up, the only independent predictors observed were time since
      diagnosis of HT >= 10 years and the number of antiHT drugs used. Presurgical BMI,
      WC, excess weight (EW), EW loss, surgical procedure, type 2 diabetes, and vitamin
      D status were not significant predictors. CONCLUSIONS: Bariatric surgery is
      associated with a high rate of HT remission. Older age, male gender, and higher
      WC differentiated hypertensive-obese from normotensive patients. After BS, longer
      duration and severity of HT were independently associated with no remission of
      HT.

PMID- 24582417
TI  - Wernicke's encephalopathy three weeks after sleeve gastrectomy.
AB  - Following bariatric surgeries for management of morbid obesity, less nutrients
      are absorbed, giving rise to complications due to vitamin deficiencies with
      frequently dramatic consequences. Neurologic complications resulting from folate,
      vitamin B12, and thiamine deficiencies have been estimated to occur in up to 16%
      of cases and present within weeks to months following bariatric surgery. Among
      bariatric surgeries, Roux-en-Y gastric bypass has been the most associated with
      such deficiencies due to both restrictive and malabsorptive components.
      Complications are less seen with restrictive surgeries. We report a case of rapid
      Wernicke's encephalopathy due to a thiamine deficiency in a young female patient
      following Sleeve gastrectomy (SG). 

PMID- 24582416
TI  - Single-incision laparoscopic bariatric surgery: a systematic review.
AB  - BACKGROUND: Single-incision laparoscopic surgery has sparked a great deal of
      interest in the surgical community in recent years, including bariatric surgery.
      However, we still do not definitively know if this type of surgical approach
      provides benefits over conventional techniques without increasing morbidity and
      mortality. OBJECTIVE: To evaluate the safety and efficacy of single-incision
      laparoscopic bariatric surgery (SILBS) compared with conventional laparoscopic
      bariatric surgery (CLBS). MATERIALS AND METHODS: We searched the most important
      databases. Randomized clinical trials and observational studies comparing SILBS
      with CLBS were included. This systematic review was performed in accordance with
      the Preferred Reporting Items for Systematic Reviews and Meta-Analyses
      recommendations. RESULTS: Fourteen studies complied with the inclusion criteria
      for our analysis, which included 2357 patients (1179 SILBS group versus 1178 CLBS
      group). The duration of surgery was longer in the SILBS group and no major
      intraoperative complications were observed in these series. A small improvement
      in postoperative pain was indicated in the SILBS group. The overall morbidity
      rate was 5% in the SILBS group and 4.8% in the CLBS. There was 1 perioperative
      death in 1 study, which occurred in an adjustable gastric banding (AGB) group, at
      .1% of all cases of AGB and .005% of all SILBS cases. When cosmesis was
      evaluated, patients in the SILBS group were more satisfied with the scar outcome.
      CONCLUSION: SILBS is a feasible technique to use in selected patients. However,
      there is insufficient evidence to recommend its widespread use compared with a
      conventional approach. More studies are needed to analyze the safety of this
      technique and its possible benefits.

PMID- 24582418
TI  - Comment on: high failure rate of the laparoscopic-adjustable gastric band as a
      primary bariatric procedure.

PMID- 24582419
TI  - Esophageal rupture: a pseudo-achalasia related delayed complication after
      laparoscopic adjustable gastric banding.

PMID- 24582420
TI  - Unusual cause of bowel obstruction after laparoscopic sleeve gastrectomy.

PMID- 24582421
TI  - Reply to "Comment on: The effect of laparoscopic sleeve gastrectomy with or
      without hiatal hernia repair on gastroesophageal reflux disease in obese
      patients".

PMID- 24582422
TI  - Spinosad is a potent inhibitor of canine P-glycoprotein.
AB  - Inhibition of the drug transporter P-glycoprotein (P-gp) by the oral flea
      preventative spinosad has been suggested as the underlying cause of the drug-drug
      interaction with ivermectin. In this study, an in vitro model consisting of
      canine cells was validated to describe the inhibitory effect of drugs on canine P
      gp. In this model, ivermectin, cyclosporin, verapamil, loperamide and
      ketoconazole inhibited P-gp function with IC50 values ranging from 0.1 to 3.7
      MUmol/L. Spinosad was a potent inhibitor of canine P-gp with an IC50 value of
      0.27 MUmol/L or 0.2 MUg/mL. The risk of spinosad causing P-gp related drug-drug
      interactions in the dog could be predicted by the IC50 value, the oral dosage and
      plasma concentrations.

PMID- 24582423
TI  - The effects of an intravenous bolus of dexmedetomidine following extubation in a
      mixed population of dogs undergoing general anaesthesia and surgery.
AB  - An observer blinded, placebo controlled study evaluated the effects of 62.5
      MUg/m(2) dexmedetomidine administered IV on recovery from isoflurane anaesthesia
      in dogs. Forty-four healthy dogs, weighing 1.8-19.95 kg, presented for surgery
      that was expected to cause mild to moderate pain were studied. All were
      premedicated with 125 MUg/m(2) dexmedetomidine and 20 MUg/kg buprenorphine IM.
      Anaesthesia was induced with propofol and maintained with isoflurane. Non
      steroidal anti-inflammatory drugs and local anaesthetics were administered as
      appropriate. Immediately prior to extubation dogs were treated with
      dexmedetomidine 62.5 MUg/m(2) (group D) or an equivalent volume of heparinised
      saline (S). Assessments of heart rate, respiratory rate, pain (short form Glasgow
      composite pain scale [SF-GCPS], dynamic interactive visual analogue scale
      [DIVAS]), sedation (simple descriptive scale [SDS], DIVAS) and mechanical
      nociceptive threshold (MNT) were performed immediately before premedication, 20
      min later, at the time of test drug administration (T0) and at 15-30 min
      intervals for four hours (T240 min). Recovery quality was scored 0 - 3 (SDS).
      Data were analysed with Student's t and Mann-Whitney U tests, two-way ANOVA and
      Fisher's exact test. Significantly fewer poor quality recoveries were observed in
      group D (D 2 [1-3]; S 2 [0-3]; P=0.02), however, sedation was increased in group
      D compared to group S from T15 to T150 min (P=0.0001). Pain scores were lower in
      group D compared to group S from T15 to T120 min (P=0.001), but the requirement
      for additional analgesia in the first 4h following extubation was not different
      between groups. Dexmedetomidine may decrease the incidence of poor quality
      anaesthetic recoveries in dogs.

PMID- 24582424
TI  - Outcome following major hepatic resection in the elderly patients.
AB  - Recent advances in operative techniques, anaesthesiologic management and
      intensive care have greatly reduced morbidity and mortality of major hepatectomy
      allowing a progressive broadening of its indications by including patients with
      chronic liver disorders as well as elderly subjects. It is apparent that with the
      aging population, more elderly patients are being referred for surgery. Selecting
      appropriate candidates for surgical resection is therefore crucial to maximize
      the benefit derived from surgery. Nevertheless, it is not clear whether advanced
      age itself increases surgical risk or additional age-independent variables are
      associated with higher operative morbidity. Regardless of the indications for
      surgery and the extent of planned liver resections, this population is more
      likely to suffer from relevant disorders. Previous studies on the safety of major
      liver resections in the elderly patients cite morbidity and mortality rates of
      approximately 30-40% and 4-5% respectively. In addition, hepatic resections for
      hepatocellular carcinoma or colorectal liver metastases have been reported as
      safe in the elderly as in the younger population. Nevertheless, a small number of
      investigations studied the outcome of major hepatectomy in the population over 70
      years of age. The aim of our study was to evaluate overall experience with liver
      resections in the elderly population by comparing the early as well as the long
      term outcome of the procedure in 70 years and older versus the less than 70 age
      group and to identify whether the age of patients alone is associated with
      increased rate and severity of postoperative complications.

PMID- 24582425
TI  - Re-inoculation strategies enhance the degradation of emerging pollutants in
      fungal bioaugmentation of sewage sludge.
AB  - The use of Trametes versicolor has been partially successful in the removal of
      some pharmaceuticals from sewage sludge in laboratory-scale biopile systems. The
      application of two strategies for the re-inoculation of biomass was assessed
      during the fungal bioaugmentation of non-sterile sludge (42-d treatment) as an
      approach to improve the elimination of pharmaceuticals and other groups of
      emerging pollutants. Globally, the re-inoculation of biopiles with blended
      mycelium exerted a major effect on the removal of pharmaceuticals (86%),
      brominated-flame-retardants (81%) and UV filters (80%) with respect to the re
      inoculation with additional lignocellulosic substrate colonized by the fungus (69
      67-22%). The performance was better than that of the analogous non-re-inoculated
      systems that were assayed previously for the removal of pharmaceuticals. The
      results demonstrate the ability of T. versicolor to remove a wide spectrum of
      emerging micropollutants under non-sterile conditions, while re-inoculation
      appears to be a useful step to improve the fungal treatment of sludge. 

PMID- 24582427
TI  - Enhanced energy conversion efficiency from high strength synthetic organic
      wastewater by sequential dark fermentative hydrogen production and algal lipid
      accumulation.
AB  - A two-stage process of sequential dark fermentative hydrogen production and
      microalgal cultivation was applied to enhance the energy conversion efficiency
      from high strength synthetic organic wastewater. Ethanol fermentation bacterium
      Ethanoligenens harbinense B49 was used as hydrogen producer, and the energy
      conversion efficiency and chemical oxygen demand (COD) removal efficiency reached
      18.6% and 28.3% in dark fermentation. Acetate was the main soluble product in
      dark fermentative effluent, which was further utilized by microalga Scenedesmus
      sp. R-16. The final algal biomass concentration reached 1.98gL(-1), and the algal
      biomass was rich in lipid (40.9%) and low in protein (23.3%) and carbohydrate
      (11.9%). Compared with single dark fermentation stage, the energy conversion
      efficiency and COD removal efficiency of two-stage system remarkably increased
      101% and 131%, respectively. This research provides a new approach for efficient
      energy production and wastewater treatment using a two-stage process combining
      dark fermentation and algal cultivation. 

PMID- 24582426
TI  - Nutrient recovery from apple pomace waste by vermicomposting technology.
AB  - The present work was focused on vermicomposting apple pomace waste and its
      mixtures with straw in volume proportions of 25%, 50%, and 75%. The feasibility
      was evaluated on the basis of agrochemical properties and earthworm biomass.
      Vermicomposting was able to reduce the weight and volume of the feedstock by 65%
      and 85%, respectively. The resulting vermicomposts were characterized by slightly
      acidic to neutral pH (5.9-6.9), and optimal EC (1.6-4.4mS/cm) and C:N ratios (13
      14). The total content of nutrients increased during vermicomposting for all of
      the treatments with the following average final values: N=2.8%, P=0.85%, K=2.3%,
      and Mg=0.38%. The addition of straw to apple pomace did not enhance earthworm
      biomass, but did increase the available content of nutrients during
      vermicomposting. The data reveals that vermicomposting is a suitable technology
      for the decomposition of apple pomace waste into a value added product. 

PMID- 24582428
TI  - Changing collecting strategies of the clam Donax serra Roding (Bivalvia:
      Donacidae) during the Pleistocene at Pinnacle Point, South Africa.
AB  - South Africa's Middle Stone Age (MSA) coastal sites have played a prominent role
      in documenting early evidence of systematic shellfish collection and adaptation
      to aquatic environments in the context of anatomically modern humans. Pinnacle
      Point 13B cave is important among these MSA sites not only because it holds the
      earliest yet known evidence for human use of marine resources (~162 ka [thousands
      of years ago]), but because shellfish observations have been integrated more
      fully into discussions of MSA adaptations. This is particularly the case of Donax
      serra procurement on sandy beaches, where skills that are usually indicative of
      an aspect of behavioural modernity (in the context of hunting) were apparently
      used. In this paper, D. serra from 110 to 91 ka old assemblages are studied in
      detail by way of metrical analyses and relevant biological and ecological
      literature of this species. Existing seasonality studies derived from oxygen
      isotope analyses on the same molluscs are incorporated into this reconstruction.
      Shellfish appear to have been collected in winter over many millennia when D.
      serra are most nutritious due to high gonad content. A dramatic change in
      collection strategies took place during the same millennia-long period. Earliest
      systematic collection of D. serra consisted of mostly unselective procurement of
      animals in terms of shell size along the tidal gradient and beach depth. In later
      visits, people collected mostly larger individuals by narrowing their collection
      to the mid-intertidal. This change increased the efficiency of D. serra
      collection, which reflects a positive adaptive behaviour that endured into Later
      Stone Age (LSA) times. 

PMID- 24582430
TI  - [Neurofibromatosis type 2 and its head and neck manifestations: literature review
      and population study in the Community of Cantabria and the province of Las
      Palmas].
AB  - INTRODUCTION AND OBJECTIVES: Neurofibromatosis type 2 (NF2) is an infrequent
      autosomal dominant disease characterised by the appearance of viii nerve
      schwannomas, meningiomas and ocular abnormalities. Incidence of 1:25,000 and
      prevalence above 1:80,000 are estimated in general. The objectives of our study
      were to determine current prevalence of NF2 in the Community of Cantabria and the
      province of Las Palmas, and its head and neck manifestations. MATERIAL AND
      METHODS: This was a population-based, retrospective study in 3 tertiary
      hospitals. RESULTS: The study population showed prevalence of 1:600,000 in the
      Community of Cantabria and 1:280,000 in the province of Las Palmas. The most
      frequently diagnosed tumour was acoustic neuroma (n=15), followed by trigeminal
      neurinoma (n=2) and vagus (n=1). CONCLUSIONS: Cases of NF2 are infrequent in
      Cantabria and Las Palmas, lower than that reported in the literature. The most
      frequently described head and neck tumour in the literature is acoustic neuroma,
      followed by schwannoma of cranial nerves v and x. Other tumours such as nasal,
      laryngeal, chorda tympani or cranial nerve vii schwannomas are also described.
      The most frequent ENT manifestation is hearing loss, especially unilateral,
      followed by cervical mass, tinnitus and headache. Early diagnosis and
      multidisciplinary management in specialised centres could improve life expectancy
      and quality of life for these patients.

PMID- 24582431
TI  - Assessment of vocal quality following treatment of advanced pharyngo-laryngeal
      carcinoma with a protocol of organ preservation.
AB  - INTRODUCTION AND OBJECTIVES: Advanced laryngeal and pharyngeal cancer, as well as
      methods to treat them, have a direct impact on voice function, speech
      communication and deglutition. Such alterations in function can influence
      employability and general quality of life. PATIENTS AND METHODS: To characterise
      the vocal status of the patients treated with an organ-preservation protocol, we
      report the voice outcomes of 17 patients who were alive and disease free at the
      time of the survey, with a minimum follow-up of 6 months, after a combination of
      radiotherapy and chemotherapy to treat advanced cancer. Objective voice
      assessment by means of spectrographic analysis, the GRBAS perceptual analysis
      system and the Voice Handicap Index was the methodology followed, which we
      suggest could be used in future large-scale investigations. RESULTS: Normal or
      slightly dysphonic voices were observed in 5 patients (29.4%) and moderate/severe
      in 12 (70.6%). Spectrographically, the 17 samples were classified as normal in 4
      cases (23.4%), Grade I in 3 cases (17.6%), Grade II in 3 (17.6%), Grade III in 4
      (23.5%) and Grade IV in 2 (11.7%). The Voice Handicap Index questionnaire, which
      was completed by the patients themselves, gave normal results in all the patients
      except for 4 (23.5%). CONCLUSIONS: The voice acoustic analysis of this series
      shows that the damage related to the organ-preservation protocol displays a
      relatively wide range of voice function outcomes. To characterise the vocal
      status of these patients reliably, we propose using homogeneous instruments
      (spectrography, GRBAS scale, Maximum Phonation Time and Voice Handicap Index) in
      future meta-analyses.

PMID- 24582432
TI  - The role of regulatory T-cells in glioma immunology.
AB  - Despite recent advances in treatment, the prognosis for glioblastoma multiforme
      (GBM) remains poor. The lack of response to treatment in GBM patients may be
      attributed to the immunosuppressed microenvironment that is characteristic of
      invasive glioma. Regulatory T-cells (Tregs) are immunosuppressive T-cells that
      normally prevent autoimmunity when the human immune response is evoked; however,
      there have been strong correlations between glioma-induced immunosuppression and
      Tregs. In fact, induction of Treg activity has been correlated with glioma
      development in both murine models and patients. While the exact mechanisms by
      which regulatory T-cells function require further elucidation, various cytokines
      such as interleukin-10 (IL-10) and transforming growth factor-beta (TFG-beta)
      have been implicated in these processes and are currently under investigation. In
      addition, hypoxia is characteristic of tumor development and is also correlated
      with downstream induction of Tregs. Due to the poor prognosis associated with
      immunosuppression in glioma patients, Tregs remain a promising area for
      immunotherapeutic research. 

PMID- 24582433
TI  - The benefits of a dual led consultant approach for microsurgical procedures.

PMID- 24582434
TI  - Structural insights into the inhibition of Wnt signaling by cancer antigen
      5T4/Wnt-activated inhibitory factor 1.
AB  - The tumor antigen 5T4/WAIF1 (Wnt-activated inhibitory factor 1; also known as
      Trophoblast glycoprotein TPBG) is a cell surface protein targeted in multiple
      cancer immunotherapy clinical trials. Recently, it has been shown that 5T4/WAIF1
      inhibits Wnt/beta-catenin signaling, a signaling system central to many
      developmental and pathological processes. Wnt/beta-catenin signaling is
      controlled by multiple inhibitors and activators. Here, we report crystal
      structures for the extracellular domain of 5T4/WAIF1 at 1.8 A resolution. They
      reveal a highly glycosylated, rigid core, comprising eight leucine-rich repeats
      (LRRs), which serves as a platform to present evolutionarily conserved surface
      residues in the N-terminal LRR1. Structural and cell-based analyses, coupled with
      previously reported in vivo data, suggest that Tyr325 plus the LRR1 surface
      centered on a second exposed aromatic residue, Phe97, are essential for
      inhibition of Wnt/beta-catenin signaling. These results provide a structural
      basis for the development of 5T4/WAIF1-targeted therapies that preserve or block
      5T4/WAIF1-mediated inhibition of Wnt/beta-catenin signaling. 

PMID- 24582437
TI  - Norms and expectations in social decision-making.
AB  - Recent research has shown that stimulating right lateral prefrontal cortex
      (rLPFC) via transcranial direct current stimulation (tDCS) changes social norm
      compliance in economic decisions, with different types of compliance affected in
      different ways. More broadly considering the norms involved in decision-making,
      and in particular expectations held by players, can help clarify the mechanisms
      underlying these results. 

PMID- 24582435
TI  - (19)F NMR reveals multiple conformations at the dimer interface of the
      nonstructural protein 1 effector domain from influenza A virus.
AB  - Nonstructural protein 1 of influenza A virus (NS1A) is a conserved virulence
      factor comprised of an N-terminal double-stranded RNA (dsRNA)-binding domain and
      a multifunctional C-terminal effector domain (ED), each of which can
      independently form symmetric homodimers. Here we apply (19)F NMR to NS1A from
      influenza A/Udorn/307/1972 virus (H3N2) labeled with 5-fluorotryptophan, and we
      demonstrate that the (19)F signal of Trp187 is a sensitive, direct monitor of the
      ED helix:helix dimer interface. (19)F relaxation dispersion data reveal the
      presence of conformational dynamics within this functionally important
      protein:protein interface, whose rate is more than three orders of magnitude
      faster than the kinetics of ED dimerization. (19)F NMR also affords direct
      spectroscopic evidence that Trp187, which mediates intermolecular ED:ED
      interactions required for cooperative dsRNA binding, is solvent exposed in full
      length NS1A at concentrations below aggregation. These results have important
      implications for the diverse roles of this NS1A epitope during influenza virus
      infection. 

PMID- 24582436
TI  - Supra-personal cognitive control and metacognition.
AB  - The human mind is extraordinary in its ability not merely to respond to events as
      they unfold but also to adapt its own operation in pursuit of its agenda. This
      'cognitive control' can be achieved through simple interactions among
      sensorimotor processes, and through interactions in which one sensorimotor
      process represents a property of another in an implicit, unconscious way. So why
      does the human mind also represent properties of cognitive processes in an
      explicit way, enabling us to think and say 'I'm sure' or 'I'm doubtful'? We
      suggest that 'system 2 metacognition' is for supra-personal cognitive control. It
      allows metacognitive information to be broadcast, and thereby to coordinate the
      sensorimotor systems of two or more agents involved in a shared task. 

PMID- 24582438
TI  - Short communication: Is consumption of a cheese rich in angiotensin-converting
      enzyme-inhibiting peptides, such as the Norwegian cheese Gamalost, associated
      with reduced blood pressure?
AB  - Epidemiological and clinical studies have shown that angiotensin-converting
      enzyme (ACE)-inhibiting peptides derived from dairy products may decrease blood
      pressure. These peptides have been identified in many cheeses, and Gamalost, a
      traditional Norwegian cheese, is particularly rich in these peptides. The aim of
      this cross-sectional study was to examine whether frequency of Gamalost intake
      was associated with blood pressure in a Norwegian population sample. Blood
      pressure and other clinical measurements, including the factors of metabolic
      syndrome, were obtained from 168 participants (56% female, mean age = 51 yr) who
      completed a questionnaire about dietary habits and other health-related factors.
      Mean Gamalost intake was 2 servings per week. The prevalence of hypertension was
      23.8% in the population, with mean systolic and diastolic blood pressures of 128
      and 78 mmHg, respectively. Intake of Gamalost was inversely associated with
      systolic blood pressure. Each increase in frequency unit of Gamalost intake
      corresponded to a reduction in systolic blood pressure of 0.72 mmHg, after
      controlling for sex, age, education, waist circumference, physical activity,
      smoking status, and dairy food intake. Results from this study indicate that
      consumption of Gamalost (or other foods rich in ACE-inhibiting peptides) may
      reduce blood pressure.

PMID- 24582439
TI  - Short-term response in milk production, dry matter intake, and grazing behavior
      of dairy cows to changes in postgrazing sward height.
AB  - Postgrazing sward height (PGSH) can be altered to adjust the allowance of grass
      in the dairy cow's diet. This study aimed to investigate the short-term dairy cow
      response to a change in postgrazing height in early lactation. Ninety Holstein
      Friesian spring-calving cows were randomly assigned across 3 postgrazing height
      treatments (n=30): 2.7 cm (severe), 3.5 cm (low), and 4.2 cm (moderate) from
      February 14 to April 24, 2011. From April 25, animals were rerandomized within
      each treatment to graze across 2 postgrazing heights: 3.5 cm (low) or 4.5 cm
      (high). Animal production measurements were taken from April 4 to 24 (measurement
      period 1; M1) and from April 25 to May 15 (measurement period 2; M2). The 6
      treatments (n=15) of M2 were severe-low, severe-high, low-low, low-high, moderate
      low, and moderate-high. During M1, increasing postgrazing height from severe to
      low to moderate linearly increased daily milk yield (21.5, 24.6 and 25.8 kg/cow
      per day) and grass dry matter intake (GDMI; 13.2, 14.9, and 15.8 kg of DM/cow per
      day). Milk solids yield was reduced in the severe (-1,518 g/cow per day)
      treatment when compared with the low and moderate cows (1,866 g/cow per day, on
      average). The milk yield (MY) response to change in PGSH between M1 and M2 (VM1
      M2) was established using VM1-M2 MY=-1.27-1.89 * PGSHM1 + 1.51 * PGSHM2
      (R(2)=0.64). The MY response associated with each treatment between M1 and M2 (3
      wk) were -1.03 kg/cow for severe-low, 0.68 kg/cow for severe-high, -2.56 kg/cow
      for low-low, -1.11 kg/cow for low-high, -4.17 kg/cow for moderate-low, and -2.39
      kg/cow for moderate-high. The large increase in energy intake in severe-high
      between M1 and M2 was achieved through higher GDMI per minute and GDMI per bite,
      which supported the positive change in MY. Treatments low-high, moderate-low, and
      moderate-high recorded the highest overall cumulative milk yield (74 kg of milk
      solids/cow) over the 6-wk period, whereas severe-low and severe-high had the
      lowest (65 kg of MS/cow). From the animal responses observed in the present
      study, imposing a postgrazing height of 3.5 cm in early spring provides the
      opportunity to increase postgrazing height thereafter; the cow increases GDMI
      accordingly and converts the additional energy intake into milk output. The
      equations established in this paper provide a decision tool for dairy farmers to
      anticipate the animal response when postgrazing height is altered or maintained
      around the tenth week of lactation.

PMID- 24582440
TI  - Extent of linkage disequilibrium, consistency of gametic phase, and imputation
      accuracy within and across Canadian dairy breeds.
AB  - Genomic selection requires a large reference population to accurately estimate
      single nucleotide polymorphism (SNP) effects. In some Canadian dairy breeds, the
      available reference populations are not large enough for accurate estimation of
      SNP effects for traits of interest. If marker phase is highly consistent across
      multiple breeds, it is theoretically possible to increase the accuracy of genomic
      prediction for one or all breeds by pooling several breeds into a common
      reference population. This study investigated the extent of linkage
      disequilibrium (LD) in 5 major dairy breeds using a 50,000 (50K) SNP panel and 3
      of the same breeds using the 777,000 (777K) SNP panel. Correlation of pair-wise
      SNP phase was also investigated on both panels. The level of LD was measured
      using the squared correlation of alleles at 2 loci (r(2)), and the consistency of
      SNP gametic phases was correlated using the signed square root of these values.
      Because of the high cost of the 777K panel, the accuracy of imputation from lower
      density marker panels [6,000 (6K) or 50K] was examined both within breed and
      using a multi-breed reference population in Holstein, Ayrshire, and Guernsey.
      Imputation was carried out using FImpute V2.2 and Beagle 3.3.2 software.
      Imputation accuracies were then calculated as both the proportion of correct SNP
      filled in (concordance rate) and allelic R(2). Computation time was also explored
      to determine the efficiency of the different algorithms for imputation. Analysis
      showed that LD values >0.2 were found in all breeds at distances at or shorter
      than the average adjacent pair-wise distance between SNP on the 50K panel.
      Correlations of r-values, however, did not reach high levels (<0.9) at these
      distances. High correlation values of SNP phase between breeds were observed
      (>0.94) when the average pair-wise distances using the 777K SNP panel were
      examined. High concordance rate (0.968-0.995) and allelic R(2) (0.946-0.991) were
      found for all breeds when imputation was carried out with FImpute from 50K to
      777K. Imputation accuracy for Guernsey and Ayrshire was slightly lower when using
      the imputation method in Beagle. Computing time was significantly greater when
      using Beagle software, with all comparable procedures being 9 to 13 times less
      efficient, in terms of time, compared with FImpute. These findings suggest that
      use of a multi-breed reference population might increase prediction accuracy
      using the 777K SNP panel and that 777K genotypes can be efficiently and
      effectively imputed using the lower density 50K SNP panel. 

PMID- 24582442
TI  - Changes on expected taste perception of probiotic and conventional yogurts made
      from goat milk after rapidly repeated exposure.
AB  - Goat milk yogurt is an excellent source of fatty acids, protein, and minerals;
      however, it is not well accepted by many consumers, due to its typical flavor
      derived from caprylic, capric, and caproic acids present in this milk and dairy
      products. Recently, the repeated-exposure test has been used to increase the
      consumption of particular foods. This methodology has been used to increase
      children's willingness to eat food in some settings and has also been used to
      reduce sodium in soup. Based on these considerations, the aim of this study was
      to investigate whether repeated exposures may increase acceptance of both goat
      milk yogurt and probiotic goat milk yogurt. In a pre-exposure session, a total of
      45 panelists (28 females and 17 males) from southeastern Brazil, who were not
      used to consuming dairy goat milk, evaluated the expected taste perception and
      the perceived liking after tasting 3 yogurt preparations. Then, consumers were
      randomly divided into 3 groups and participated in rapidly repeated exposure
      sessions performed within 6 d. Each panelist consumed only the yogurt that he or
      she would be exposed to. The day after the exposure sessions, all panelists
      returned to participate in the postexposure session and were asked to evaluate
      acceptance, familiarity, and the "goaty taste" characteristic of each yogurt.
      Regarding the expected liking before tasting, results showed higher expectations
      for cow milk yogurt compared with goat milk yogurt, which proved that consumers
      were not familiar with the goat milk yogurt. Likewise, only cow milk yogurt
      presented high acceptance and familiarity rates, confirming that these panelists
      were used to consuming cow milk products. With respect to the rapidly repeated
      exposure, 6 d were enough to significantly increase the consumers' familiarity
      with goat milk yogurt and probiotic goat milk yogurt. However, this method was
      not suitable to significantly increase the acceptance of such products.
      Nonetheless, a correlation existed between the exposure sessions and the increase
      in acceptance of the exposure groups. Thus, hypothetically, the increasing of
      exposure sessions could be a strategy to increase goat milk product acceptance. 

PMID- 24582441
TI  - Casein synthesis is independently and additively related to individual essential
      amino acid supply.
AB  - Specific AA affect rates of milk protein synthesis in the mammary glands of
      lactating cows. The objective of this study was to quantify the rate of alphaS1
      casein synthesis in response to Ile, Leu, Met, and Thr supplementation, and to
      test the single-limiting AA theory for milk protein synthesis by exploring
      interactions among these AA. Effects of Ile, Leu, Met, and Thr were studied in
      vitro with a composite design containing a central point repeated 4 times, with 2
      axial points per AA and a complete 2(4) factorial. Other AA were at the
      concentration in Dulbecco's modified Eagle medium/F12 medium (DMEM). The
      experiment was replicated with mammary tissue from 5 lactating cows. Mammary
      tissue slices (0.12 +/- 0.02 g) were incubated for 4h at 37 degrees C in 5 mL of
      treatment medium containing (2)H5-Phe. Caseins were precipitated from cell
      homogenate supernatants. Enrichment with (2)H5-Phe of the N[34]LLRFFVAPFPE
      alphaS1 peptide was determined by matrix-assisted laser desorption/ionization
      tandem time-of-flight (MALDI-TOF-TOF), which was used to determine enrichment of
      Phe in the transfer (t)RNA pool and alphaS1-casein fractional synthesis rates
      (CFSR). Data were analyzed with a polynomial mixed model containing linear,
      quadratic, and 2-factor interactions for Ile, Leu, Met, and Thr, and cow and
      residual as random factors. Interactions were not significant at P<0.1 and were
      removed from the model. Increasing concentrations of Ile, Leu, Met, and Thr
      simultaneously increased CFSR curvilinearly with a predicted maximum response of
      4.32 +/- 0.84%/h at 63% of DMEM concentrations. The maximum response to each of
      the 4 AA was at 71, 49, 60, and 32% of the concentration in DMEM, for Ile, Leu,
      Met, and Thr, respectively. These values correspond to 270, 120, 440, and 140%
      the plasma concentrations of Ile, Leu, Met, and Thr observed in lactating cows
      fed to meet National Research Council requirements, respectively. The CFSR
      estimated at those maxima were similar among AA (3.6 +/- 0.6%/h). Individual AA
      effects on CFSR did not correlate with mammalian target of rapamycin (mTOR)
      signaling. Independent responses of CFSR to individual essential AA observed in
      this study contradict the single-limiting AA theory assumed in current
      requirement systems. The saturable responses in CFSR to these 4 AA also highlight
      the inadequacy of using a fixed postabsorptive AA efficiency approach for
      determining AA requirements for milk protein synthesis.

PMID- 24582443
TI  - Stocking density, milking duration, and lying times of lactating cows on Canadian
      freestall dairy farms.
AB  - Lying time is an important measure of cow comfort, and the lying behavior of
      dairy cattle can now be recorded automatically with the use of accelerometers. To
      assess the effect that stall stocking density and the time that cows spend away
      from the home pen being milked has on the lying behavior of Holstein cattle, a
      total of 111 commercial freestall dairy farms were visited in Canada.
      Accelerometers were used to automatically record the lying behavior of 40 focal
      cows per farm. Total duration of lying, lying bout frequency, and the mean
      duration of lying bouts were calculated. Pen population was the total number of
      cows in the pen. To calculate stall stocking density (%) the number of cows in
      the pen and the number of useable stalls were counted and multiplied by 100, and
      the length * width of the pen was divided by the number of cows in the pen to
      calculate area/cow (m(2)). Time away from the pen per day was recorded from when
      the first cow in each pen was taken out of the home pen for milking until the
      last cow returned to the home pen after milking, and this time was multiplied by
      daily milking frequency. The median value for lying duration at the farm level
      was 10.6h/d, with 10.5 lying bouts/d, and a median lying bout duration of 1.2h.
      Stall stocking density ranged from 52.2 to 160.0%, with very few farms (7%)
      stocking at greater than 120%. Although stall stocking density was not
      significantly correlated with lying behavior, the results showed that no farm
      with stocking density greater that 100% achieved an average herd lying duration
      of 12h/d or higher, whereas 21.6% of farms with a stocking density of 100% or
      less did achieve the target lying time of >= 12 h/d, as recommended by the
      Canadian Code of Practice (chi(2)=4.86, degrees of freedom = 1). Area/cow (m(2))
      was not correlated with any aspect of lying behavior, but regardless of space per
      cow, pen population was correlated with daily frequency and duration of lying
      bouts. As the number of cows in the pen increased, lying daily bout frequency
      increased (correlation coefficient = 0.24) and lying bout duration decreased
      (correlation coefficient = -0.30). Lying behavior was affected by the time the
      cows were away from the pen being milked. When cows were away from the pen for
      longer than 3.7h/d, no farm achieved the recommended herd median lying time of
      12h/d or longer. These results suggest that providing 1 stall for each cow in the
      pen and minimizing time away from the pen are important factors if cattle are to
      achieve the recommended daily lying duration of 12h/d.

PMID- 24582444
TI  - Short communication: Prediction of retention pay-off using a machine learning
      algorithm.
AB  - Replacement decisions have a major effect on dairy farm profitability. Dynamic
      programming (DP) has been widely studied to find the optimal replacement policies
      in dairy cattle. However, DP models are computationally intensive and might not
      be practical for daily decision making. Hence, the ability of applying machine
      learning on a prerun DP model to provide fast and accurate predictions of
      nonlinear and intercorrelated variables makes it an ideal methodology. Milk class
      (1 to 5), lactation number (1 to 9), month in milk (1 to 20), and month of
      pregnancy (0 to 9) were used to describe all cows in a herd in a DP model. Twenty
      seven scenarios based on all combinations of 3 levels (base, 20% above, and 20%
      below) of milk production, milk price, and replacement cost were solved with the
      DP model, resulting in a data set of 122,716 records, each with a calculated
      retention pay-off (RPO). Then, a machine learning model tree algorithm was used
      to mimic the evaluated RPO with DP. The correlation coefficient factor was used
      to observe the concordance of RPO evaluated by DP and RPO predicted by the model
      tree. The obtained correlation coefficient was 0.991, with a corresponding value
      of 0.11 for relative absolute error. At least 100 instances were required per
      model constraint, resulting in 204 total equations (models). When these models
      were used for binary classification of positive and negative RPO, error rates
      were 1% false negatives and 9% false positives. Applying this trained model from
      simulated data for prediction of RPO for 102 actual replacement records from the
      University of Wisconsin-Madison dairy herd resulted in a 0.994 correlation with
      0.10 relative absolute error rate. Overall results showed that model tree has a
      potential to be used in conjunction with DP to assist farmers in their
      replacement decisions. 

PMID- 24582445
TI  - Relationships between dry matter content, ensiling, ammonia-nitrogen, and ruminal
      in vitro starch digestibility in high-moisture corn samples.
AB  - The objectives of the study were (1) to determine relationships between high
      moisture corn (HMC) dry matter (DM), ammonia-N [% of crude protein (CP)], and
      soluble CP concentrations, and pH, with 7-h ruminal in vitro starch digestibility
      (ivStarchD), and (2) to evaluate the effect of ensiling on pH, ammonia-N, soluble
      CP, and ivStarchD measurements in HMC. A data set comprising 6,131 HMC samples
      (55 to 80% DM) obtained from a commercial feed analysis laboratory was used for
      this study. Month of sample submittal was assumed to be associated with length of
      the ensiling period. Data for month of sample submittal were analyzed using Proc
      Mixed in SAS (SAS Institute Inc., Cary, NC) with month as a fixed effect.
      Regressions to determine linear and quadratic relationships between ivStarchD and
      ammonia-N, soluble CP, pH, and DM content were performed using Proc Mixed. The
      ivStarchD increased by 9 percentage units from October to August of the following
      year. Similar results were observed for ammonia-N and soluble CP with increases
      from 1.8 to 4.6% of CP and 31.3 to 46.4% of CP, respectively, from October to
      August of the following year. Ammonia-N was positively related to ivStarchD
      (R(2)=0.61). The DM content of HMC at silo removal was negatively related
      (R(2)=0.47) to ivStarchD with a decrease of 1.6 percentage units in ivStarchD per
      1-percentage-unit increase in DM content. The pH of HMC was negatively related to
      ammonia-N (R(2)=0.53), soluble CP (R(2)=0.57), and ivStarchD (R(2)=0.51).
      Combined, ammonia-N, DM, soluble CP, and pH provided a good prediction of
      ivStarchD (adjusted R(2)=0.70). Increasing pH, ammonia-N, soluble CP, and
      ivStarchD values indicate that HMC may need up to 10 mo of ensiling to reach
      maximum starch digestibility. Ammonia-N, DM content, soluble CP concentration,
      and pH are good indicators of ruminal in vitro starch digestibility for high
      moisture corn. 

PMID- 24582446
TI  - Effects of short-term repeated exposure to different flooring surfaces on the
      behavior and physiology of dairy cattle.
AB  - Dairy cattle managed in some pasture-based systems such as in New Zealand are
      predominantly kept outdoors all year around, but are often taken off pasture for
      periods of time in wet weather to avoid soil damage. It is common to keep cattle
      on concrete surfaces during such "stand-off" practices and we investigated
      whether the addition of rubber matting onto concrete areas improves the welfare
      of dairy cattle. Sixteen groups of 5 cows (4 groups/treatment, 5 cows/group) were
      allocated to 1 of 4 treatments (concrete, 12-mm-thick rubber mat, 24-mm-thick
      rubber mat, or deep-bedded wood chips) and kept on these surfaces for 18 h/24h
      for 4 consecutive days (6h on pasture/24h). Each 4-d stand-off period was
      repeated 4 times (with 7 d of recovery between periods) to study the accumulated
      effects of repeated stand-off. Lying behavior was recorded continuously during
      the experiment. Gait score, stride length, hygiene score, live weight, and blood
      samples for cortisol analysis were recorded immediately before and after each
      stand-off period. Cows on wood chips spent the most time lying, and cows on
      concrete spent the least time lying compared with those on other surfaces [wood
      chips: 10.8h, 24-mm rubber mat: 7.3h, 12-mm rubber mat: 6.0 h, and concrete:
      2.8h/18 h, standard error of the difference (SED): 0.71 h]. Cows on concrete
      spent more time lying during the 6h on pasture, likely compensating for the
      reduced lying during the stand-off period. Similarly, cows on concrete spent more
      time lying on pasture between stand-off periods (concrete: 12.1h, 12-mm rubber
      mat: 11.1h, 24-mm rubber mat: 11.2h, and wood chips: 10.7h/24h, SED: 0.28 h).
      Cows on concrete had higher gait score and shorter stride length after the 4-d
      stand-off period compared with cows on the other surface types, suggesting a
      change in gait pattern caused by discomfort. Cows on rubber mats were almost 3
      times dirtier than cows on concrete or wood chips. Cortisol and live weight
      decreased for all treatment groups during the stand-off period. We observed no
      major effect of the repeated stand-off exposure. In summary, adding rubber
      matting onto concrete surfaces for stand-off purposes is beneficial for animal
      welfare. A well-managed wood chip surface offered the best welfare for dairy cows
      removed from pasture, and the findings of this study confirm that a concrete
      surface decreases the welfare of cows removed from pasture.

PMID- 24582447
TI  - Economic evaluation of participation in a voluntary Johne's disease prevention
      and control program from a farmer's perspective--The Alberta Johne's Disease
      Initiative.
AB  - The Alberta Johne's Disease Initiative (AJDI) is a Johne's disease (JD) control
      program with the goal of reducing the spread of Mycobacterium avium ssp.
      paratuberculosis (MAP) through implementation of best management practices. The
      objective was to estimate the economic benefit of participation in the AJDI. A
      decision tree was constructed in which disease prevalence, test characteristics,
      and probabilities for implementation of best management practices suggested by
      herd veterinarians were implemented. Analysis was performed using a Markov
      analysis, and input data were assigned using estimates from the AJDI and
      published data. A cost-effectiveness analysis was performed and the net benefit
      of participation (from the perspective of a dairy farmer) in the AJDI compared
      with no participation was calculated. A series of 1-way sensitivity analyses were
      used to control for uncertainty. Farms participating in the AJDI were estimated
      to have a net benefit of Can$74 per cow over the course of 10 yr. If project
      costs were covered by the participating farm, the net benefit was Can$27. In
      addition to the effects on MAP infection, a reduction in calf diarrhea was
      modeled for farms that improved their calf management through the use of
      pasteurizers. In that case, the additional costs outweighed additional revenues
      compared with the baseline analysis, resulting in a reduced net benefit of
      Can$19. Participation would not be cost effective if cows in early stages of MAP
      infection did not have decreased production and if prevalence of MAP infection
      did not increase on farms with poor management. A limitation of the study,
      despite high uncertainty in some input parameters, was the lack of knowledge
      regarding changes in prevalence on farms with various management strategies. In
      conclusion, participation in the AJDI was cost effective for the average Alberta
      dairy farm.

PMID- 24582448
TI  - Changes in the dynamics of Coxiella burnetii infection in dairy cattle: an
      approach to match field data with the epidemiological cycle of C. burnetii in
      endemic herds.
AB  - This study aimed to evaluate changes in the epidemiological status of Coxiella
      burnetii in dairy cattle herds to better understand the epidemiology of the
      infection and to predict its evolution. Bulk-tank milk (BTM) and serum samples
      were collected from 94 dairy cattle herds and analyzed by ELISA (BTM and sera)
      and PCR (BTM) in study 1 (S1). Two years later (study 2; S2), the same farms were
      visited with a similar sampling approach. To estimate seroconversion during this
      period, blood samples were collected from the maximum possible number of animals
      surveyed in S1. Environmental samples were collected in S2 to identify active
      shedding. Farms were allocated into 3 different categories in each study
      according to PCR and ELISA results: category A, with BTM ELISA and PCR positive
      herds and at least 1 seropositive animal; category B, with BTM ELISA or PCR
      positive herds or individual sera positive; and category C, with all negative
      results among herds. Changes in herd category between S1 and S2 were grouped in 9
      classes. Two statistical models, one to search for drives of within-herd changes
      in C. burnetii infection status and another to look for variables modulating
      individual changes in C. burnetii antibody level, were built. Several herds in
      category A in S1 remained in that category 2 yr later, indicating that C.
      burnetii can remain within a herd for a long time. Most of the herds with
      seroconversion and detection of the bacterium in the environment belonged to
      category A, suggesting active and recent infections. Changes in the
      epidemiological status of herds were driven by local densities of domestic
      ruminants, showing the implication of neighbor reservoirs; whereas individual
      changes in antibody levels were modulated by variation in the epidemiological
      status of herds. Observed changes in epidemiological status allowed depiction of
      the hypothesized life cycle of C. burnetii within dairy cattle herds, which
      should be tested by future long-term series studies on C. burnetii infection to
      help fitting control measures (e.g., vaccination) to within-herd C. burnetii
      status.

PMID- 24582449
TI  - Effect of cell-surface components and metabolites of lactic acid bacteria and
      probiotic organisms on cytokine production and induction of CD25 expression in
      human peripheral mononuclear cells.
AB  - In the current study, the relative contribution of cell-surface components (CSC)
      and cell-free supernatants (CFS) in the immuno-modulatory properties of 17
      strains of probiotic and lactic acid bacteria (LAB) was assessed. The production
      of pro- and antiinflammatory cytokines including IL-2, IL-4, IL-10, IL-12 p70,
      IFN-gamma, tumor necrosis factor-alpha (TNF-alpha), and transforming growth
      factor-beta was measured at different time points after stimulation of buffy coat
      derived-peripheral blood mononuclear cells (PBMC) from healthy donors with CSC
      and CFS of probiotic and LAB. Results showed that CSC of probiotic and LAB
      strains induced production of T helper 1 and 2 type cytokines. Transforming
      growth factor-beta was stimulated at highest concentrations, followed by IL-10
      and TNF-alpha. The CFS of all tested bacterial strains induced PBMC for
      significantly high levels of IL-10 secretion compared with unstimulated cells,
      but the values were less than lipopolysaccharide-stimulated cells. Cytokines due
      to CFS stimulation showed declined concentration for IL-2, TNF-alpha, and IL-4,
      and complete disappearance of IL-12, IFN-gamma, and transforming growth factor
      beta in the cultured medium at 96 h of incubation. Results of cytokine data
      demonstrate proinflammatory TNF-alpha immune responses are mainly directed
      through cell-surface structures of probiotic and LAB, but antiinflammatory immune
      responses are mediated both by metabolites and cell-surfaces of these bacteria.
      The induction of CD4(+)CD25(+) regulatory T cells after stimulation of PBMC with
      CSC and CFS of probiotic and LAB showed regulatory T cell activity appeared to be
      influenced both by the CSC and metabolites, but was principally triggered by cell
      surfaces of probiotic and LAB strains.

PMID- 24582450
TI  - Short communication: Prevalence of methicillin resistance in coagulase-negative
      staphylococci and Staphylococcus aureus isolated from bulk milk on organic and
      conventional dairy farms in the United States.
AB  - The objective of this study was to evaluate the presence of methicillin-resistant
      Staphylococcus aureus and coagulase-negative Staphylococcus spp. in bulk tank
      milk samples from 288 organic and conventional dairy farms located in New York,
      Wisconsin, and Oregon from March 2009 to May 2011. Due to recent publications
      reporting the presence mecC (a mecA homolog not detected by traditional mecA
      based PCR methods), a combination of genotypic and phenotypic approaches was used
      to enhance the recovery of methicillin-resistant organisms from bulk tank milk.
      In total, 13 isolates were identified as methicillin resistant: Staph. aureus
      (n=1), Staphylococcus sciuri (n=5), Staphylococcus chromogenes (n=2),
      Staphylococcus saprophyticus (n=3), Staphylococcus agnetis (n=1), and Macrococcus
      caseolyticus (n=1). The single methicillin-resistant Staph. aureus isolate was
      identified from an organic farm in New York, for an observed 0.3% prevalence at
      the farm level. The methicillin-resistant coagulase-negative staphylococci
      prevalence was 2% in the organic population and 5% in the conventional
      population. We did not identify mecC in any of the isolates from our population.
      Of interest was the relatively high number of methicillin-resistant Staph. sciuri
      recovered, as the number of isolates from our study was considerably higher than
      those recovered from other recent studies that also assessed milk samples. Our
      research suggests that the presence of a potential methicillin-resistant
      Staphylococcus reservoir in milk, and likely the dairy farm population in the
      United States, is independent of the organic or conventional production system. 

PMID- 24582451
TI  - Evaluation of gonadotropin-releasing hormone hydrogen chloride at 3 doses with
      prostaglandin F2alpha for fixed-time artificial insemination in dairy cows.
AB  - The objectives of the current study were to evaluate the efficacy and field
      safety of GnRH HCl administered at 3 doses in fixed-time artificial insemination
      (FTAI) programs (Ovsynch) in dairy cows. A common protocol was conducted at 6
      commercial dairies. Between 188 and 195 cows were enrolled at each site (total
      enrolled = 1,142). Cows had body condition scores >= 2 and <= 4, were between 32
      to 140 d in milk, and were clinically healthy. Within pen and enrollment day
      (enrollment cohort), cows were assigned randomly in blocks of 4 to each of 4
      treatments: (1) 25mg of PGF2alpha on d 7 with FTAI 72 +/- 2 h later (control);
      (2) 100 MUg of GnRH on d 0, d 7 a dose of 25mg of PGF2alpha, and the second
      administration of 100 MUg of GnRH (T100) administered either at 48 +/- 2 h (d 9)
      after PGF2alpha with FTAI 24 +/- 2 h later or 56 +/- 2 h (d 9) after PGF2alpha
      and FTAI 17 +/- 2 h later; (3) same as T100 with both injections of 150 MUg of
      GnRH (T150); and (4) same as T100 with both injections of 200 MUg of GnRH (T200).
      Three sites selected the first option and 3 sites selected the second option for
      the timing of the second injection of all doses of GnRH. Cows were observed daily
      for signs of estrus and adverse clinical signs. Cows not returning to estrus had
      pregnancy diagnosis between 42 and 65 d following FTAI. Pregnancies per FTAI
      (P/FTAI) were analyzed as a binary variable (1 = pregnant, 0 = not pregnant)
      using a generalized linear mixed model with a binomial error distribution and a
      logit link function. The statistical model included fixed effects for treatment,
      random effects of site, site by treatment, enrollment cohort within site, and
      residual. Parity (first vs. second or greater) was included as a covariate. For
      demonstration of effectiveness, alpha=0.05 and a 2-tailed test were used. Fifty
      two cows were removed from the study because of either deviation from the
      protocol, injury, illness, culling, or death. Among the remaining 1,090 cows,
      33.9% were primiparous and 66.1% were multiparous. Back-transformed least squares
      means for P/FTAI were 17.1, 27.3, 29.1, and 32.2% for control, T100, T150 and
      T200, respectively. The P/FTAI for each GnRH dose differed from that of the
      control. No differences were detected in P/FTAI between GnRH doses. No treatment
      related adverse events were observed. Mastitis was the most frequently observed
      adverse clinical sign, followed by lameness and pneumonia. This study documents
      the efficacy and safety of doses of 100 to 200 MUg of GnRH as the HCl salt when
      used in Ovsynch programs.

PMID- 24582452
TI  - Evaluation of the effects of ultraviolet light on bacterial contaminants
      inoculated into whole milk and colostrum, and on colostrum immunoglobulin G.
AB  - Raw milk and colostrum can harbor dangerous microorganisms that can pose serious
      health risks for animals and humans. According to the USDA, more than 58% of
      calves in the United States are fed unpasteurized milk. The aim of this study was
      to evaluate the effect of UV light on reduction of bacteria in milk and
      colostrum, and on colostrum IgG. A pilot-scale UV light continuous (UVC) flow
      through unit (45 J/cm(2)) was used to treat milk and colostrum. Colostrum and
      sterile whole milk were inoculated with Listeria innocua, Mycobacterium
      smegmatis, Salmonella serovar Typhimurium, Escherichia coli, Staphylococcus
      aureus, Streptococcus agalactiae, and Acinetobacter baumannii before being
      treated with UVC. During UVC treatment, samples were collected at 5 time points
      and bacteria were enumerated using selective media. The effect of UVC on IgG was
      evaluated using raw colostrum from a nearby dairy farm without the addition of
      bacteria. For each colostrum batch, samples were collected at several different
      time points and IgG was measured using ELISA. The UVC treatment of milk resulted
      in a significant final count (log cfu/mL) reduction of Listeria monocytogenes
      (3.2 +/- 0.3 log cfu/mL reduction), Salmonella spp. (3.7 +/- 0.2 log cfu/mL
      reduction), Escherichia coli (2.8 +/- 0.2 log cfu/mL reduction), Staph. aureus
      (3.4 +/- 0.3 log cfu/mL reduction), Streptococcus spp. (3.4 +/- 0.4 log cfu/mL
      reduction), and A. baumannii (2.8 +/- 0.2 log cfu/mL reduction). The UVC
      treatment of milk did not result in a significant final count (log cfu/mL)
      reduction for M. smegmatis (1.8 +/- 0.5 log cfu/mL reduction). The UVC treatment
      of colostrum was significantly associated with a final reduction of bacterial
      count (log cfu/mL) of Listeria spp. (1.4 +/- 0.3 log cfu/mL reduction),
      Salmonella spp. (1.0 +/- 0.2 log cfu/mL reduction), and Acinetobacter spp. (1.1
      +/- 0.3 log cfu/mL reduction), but not of E. coli (0.5 +/- 0.3 log cfu/mL
      reduction), Strep. agalactiae (0.8 +/- 0.2 log cfu/mL reduction), and Staph.
      aureus (0.4 +/- 0.2 log cfu/mL reduction). The UVC treatment of colostrum
      significantly decreased the IgG concentration, with an observed final mean IgG
      reduction of approximately 50%. Development of new methods to reduce bacterial
      contaminants in colostrum must take into consideration the barriers imposed by
      its opacity and organic components, and account for the incidental damage to IgG
      caused by manipulating colostrum.

PMID- 24582453
TI  - Complete genomic sequence analyses of the first group A giraffe rotavirus reveals
      close evolutionary relationship with rotaviruses infecting other members of the
      Artiodactyla.
AB  - Group A Rotaviruses (RVA) have been established as significant contributory
      agents of acute gastroenteritis in young children and many animal species. In
      2008, we described the first RVA strain detected in a giraffe calf (RVA/Giraffe
      wt/IRL/GirRV/2008/G10P[11]), presenting with acute diarrhoea. Molecular
      characterisation of the VP7 and VP4 genes revealed the bovine-like genotypes G10
      and P[11], respectively. To further investigate the origin of this giraffe RVA
      strain, the 9 remaining gene segments were sequenced and analysed, revealing the
      following genotype constellation: G10-P[11]-I2-R2-C2-M2-A3-N2-T6-E2-H3. This
      genotype constellation is very similar to RVA strains isolated from cattle or
      other members of the artiodactyls. Phylogenetic analyses confirmed the close
      relationship between GirRV and RVA strains with a bovine-like genotype
      constellation detected from several host species, including humans. These results
      suggest that RVA strain GirRV was the result of an interspecies transmission from
      a bovine host to the giraffe calf. However, we cannot rule out completely that
      this bovine-like RVA genotype constellation may be enzootic in giraffes. Future
      RVA surveillance in giraffes may answer this intriguing question. 

PMID- 24582454
TI  - Lestaurtinib (CEP-701) attenuates "second hit" kainic acid-induced seizures
      following early life hypoxic seizures.
AB  - Tropomyosin-related kinase receptor B (TrkB) activation has been implicated in
      epileptogenesis. We investigated hippocampal levels of phosphorylated TrkB (p
      TrkB) and potential antiepileptogenic actions of the tyrosine kinase inhibitor,
      lestaurtinib (CEP-701) in postnatal day 10 (P10) rat pups following hypoxic
      seizures (HS). Hippocampal expression of p-TrkB over total TrkB protein levels
      were assessed by immunoblot at 6, 12, or 24 h post-HS, and revealed a
      statistically significant and transient 1.5-fold increase in hippocampal p-TrkB
      12 h post-HS compared to littermate normoxic controls. To investigate the effects
      of CEP-701, pups were treated with 2 doses of CEP-701 intraperitoneally (i.p.), 3
      mg/kg/dose, immediately after and 12 h post-HS. P-TrkB levels and susceptibility
      to kainic acid (KA)-induced seizures at P14 were compared between post-HS CEP-701
      treated pups, post-HS vehicle-treated pups and normoxic littermates. Post
      treatment with CEP-701 reversed the increased TrkB phosphorylation to baseline
      normoxic levels and attenuated the HS-related enhanced susceptibility to KA
      induced seizures at P14. Given its known clinical safety profile, CEP-701 is a
      promising clinically translatable therapy to prevent epileptogenesis in the
      immature brain.

PMID- 24582455
TI  - Quality improvement by implementing an integrated oncological care pathway for
      breast cancer patients.
AB  - BACKGROUND AND AIM: In cancer care, more and more systemized approaches such as
      care pathways are used to reduce variation, reduce waiting- and throughput times
      and to improve quality of care. The aim of this study was to determine whether
      the implementation of a multidisciplinary breast cancer pathway in three
      hospitals has improved the care for breast cancer patients. METHODS:
      Retrospectively almost 800 patients with breast cancer were selected from the
      Netherlands Cancer Registry (NCR). The patients were divided in two groups:
      before implementation of the pathway in 2006-07 (baseline measurement) and those
      after implementation in 2009 (post measurement). Fourteen quality indicators were
      compared before and after the implementation of the care pathway. To estimate the
      impact of the care pathway relative to evidence based guidelines and profession
      based norms, involved project leaders were interviewed. RESULTS: Seven out of
      eight indicators with medical information and four out of five indicators with
      information about waiting- and throughput times improved. With the
      multidisciplinary meeting as key in the breast cancer care, more compliance to
      national guidelines was observed. E.g. for more patients a HER2neu test was
      performed after implementation of the pathway (from 92% to 96%, ? = 0.016) and
      more patients started with their first chemotherapy (from 33% to 45%) or their
      first radiotherapy (from 55% to 59%) within 4 weeks after surgery. CONCLUSION:
      Implementing a multidisciplinary breast cancer pathway leads to better compliance
      with the national guidelines and can improve breast cancer care.

PMID- 24582456
TI  - Immunomagnetic selection or irradiation eliminates alloreactive cells but also
      reduces anti-tumor potential of cytokine-induced killer cells: implications for
      unmanipulated cytokine-induced killer cell infusion.
AB  - BACKGROUND AIMS: Cytokine-induced killer (CIK) cells may offer a novel
      therapeutic approach for patients with malignancies relapsing after allogeneic
      stem cell transplantation. Although CIK cells display negligible alloreactivity
      and cause minimal graft versus-host-disease (GVHD), high CIK cell doses required
      during relapse may pose a risk for severe GVHD, specifically in the mismatched or
      haploidentical transplantation setting. Manipulation of CIK cells may reduce risk
      for GVHD without affecting the anti-tumor potential. METHODS: In this pre
      clinical study, we provide a detailed functional comparison of conventional and
      irradiated, CD56-enriched or T-cell receptor alpha/beta-depleted CIK cells.
      RESULTS: In vitro analysis showed retained anti-leukemic and anti-tumor potential
      after CIK cell manipulation. Even being sequentially infused into immunodeficient
      mice grafted with malignant cells, cytotoxic effects were fewest after
      irradiation but were improved by CD56 enrichment and were best with conventional
      CIK cells. Hence, considering the proliferative capacity of inoculated
      malignancies and effector cells, a single dose of conventional CIK cells resulted
      in prolonged disease-free survival and elimination of rhabdomyosarcoma cells,
      whereas sequential infusions were needed to achieve comparable results in
      leukemia-bearing mice. However, this mouse model has limitations: highly
      effective conventional CIK cells demonstrated both limited xenogenic GVHD and low
      alloreactive potential in vitro. CONCLUSIONS: Our study revealed that
      conventional CIK cells demonstrate no significant alloreactive potential but
      provide the strongest anti-tumor efficacy compared with manipulated CIK cells.
      Conventional CIK cells may therefore be tested in high numbers and short-term
      intervals in patients with impending relapse even after mismatched
      transplantation.

PMID- 24582457
TI  - Transplantation of olfactory ensheathing cells promotes the recovery of
      neurological functions in rats with traumatic brain injury associated with
      downregulation of Bad.
AB  - BACKGROUND AIMS: The neuroprotective effects of olfactory ensheathing cells
      (OECs) after transplantation have largely been known in the injured nervous
      system. However, the underlying mechanisms still must be further elucidated. We
      explored the effects of OEC transplantation on the recovery of neurophysiologic
      function and the related anti-apoptosis mechanism in acute traumatic brain
      injury. METHODS: The OECs from neonatal Sprague-Dawley rats were isolated,
      identified and labeled and then were immediately transplanted into the regions
      surrounding the injured brain site that is resulted from free-weight drop injury.
      RESULTS: Nerve growth factor and it's recepor, p75 was expressed in cultured
      OECs. Transplanted OECs survived, migrated around the injury site and
      significantly improved the neurological severe scores compared with the control
      group (P < 0.05). OEC transplantation significantly increased the number of GAP
      43-immunopositive fibers and synaptophysin-positive vesicles (P < 0.05) but
      significantly decreased the number of apoptotic cells (P < 0.05). On the
      molecular level, the expression of Bad in the OEC transplantation group was
      significantly downregulated (P < 0.05). CONCLUSIONS: OEC transplantation could
      effectively improve neurological deficits in TBI rats; the underlying mechanism
      may be related with their effects on neuroprotection and regeneration induction,
      which is associated with the downregulation of the apoptotic molecule Bad.

PMID- 24582459
TI  - Enhancement of tendon-bone healing with the use of bone morphogenetic protein-2
      inserted into the suture anchor hole in a rabbit patellar tendon model.
AB  - BACKGROUND AIMS: Suture anchor fixation failure has been reported as a result of
      anchor loosening and migration during the tendon-bone repair. The aim of this
      study was to evaluate the effects of bone morphogenetic protein-2 (BMP-2)
      inserted into the suture anchor hole on bone formation and the tendon-bone
      healing. METHODS: Both back legs of 24 New Zealand White rabbits (n = 48) were
      used in this study. A metal suture anchor was then placed 5 mm below the cortex.
      In the control group, the space over the eyelet of the anchor (suture anchor
      hole) was not filled. In the experimental group, the suture anchor hole was
      filled with 0.1 mL of fibrin glue (group 2) or collagen gel (group 3) with 1 MUg
      BMP-2. Histologic analysis, real-time-polymerase chain reaction, bone density and
      failure load measurement were performed, and differences were analyzed at 4 and 8
      weeks. RESULTS: Histologic analysis revealed more abundant new bone, mature bone
      and organized fibrocartilage at the tendon-bone interface at 4 and 8 weeks in
      groups in which BMP-2 was applied. At 8 weeks, the failure load of groups 1, 2
      and 3 was significantly different among the three groups (P = 0.01). After post
      hoc Tukey test, the failure load of group 2 was significantly higher than that of
      group 1 (P = 0.01). CONCLUSIONS: BMP-2, administrated as described in this study,
      improved tendon-bone healing and bone formation, resulting in improved
      biomechanical strength of the tendon-bone junction.

PMID- 24582458
TI  - Low rate of infusional toxicity after expanded cord blood transplantation.
AB  - BACKGROUND AIMS: Umbilical cord blood (CB) is used with increasing frequency to
      restore hematopoiesis in patients with bone marrow transplant who lack a suitable
      human leukocyte antigen-matched donor. CB transplantation is limited by low cell
      doses and delays in neutrophil and platelet engraftment. CB progenitors expanded
      ex vivo before transplantation provide more rapid hematopoietic and immune
      reconstitution as well as less engraftment failure compared with unmanipulated
      CB. However, the safety of infusing double and ex vivo-expanded CB has not been
      systematically examined. METHODS: We reviewed the immediate adverse events (AE)
      associated with the infusion of CB occurring within 24 hours in 137 patients
      enrolled in clinical CB transplant trials at the MD Anderson Cancer Center from
      February 2004 to May 2010. All patients received an unmanipulated CB unit
      followed by infusion of a second unmanipulated CB unit or a second CB unit
      expanded ex vivo with the use of cytokines in a liquid culture system or in
      mesenchymal stromal cell co-cultures. RESULTS: A total of three grade 2 and two
      grade 3 infusion reactions occurred within 24 hours of CB transplantation. This
      resulted in an AE rate of 3.7%. The majority of AEs manifested as signs of
      hypertension. No association with patient age, sex, disease status,
      premedication, ABO compatibility or total infusion volume was observed. In
      summary, the incidence of infusion-related toxicities in patients who receive
      unmanipulated and ex vivo-expanded double CB transplantation is low. CONCLUSIONS:
      We conclude that the infusion of unmanipulated followed by expanded CB products
      is a safe procedure associated with a low probability of inducing severe
      reactions.

PMID- 24582460
TI  - Age of diabetes diagnosis and diabetes duration associate with glycated
      haemoglobin.
AB  - An earlier age of diagnosis (r=-0.28, p<0.0001) and longer duration of type 2
      diabetes (r=0.26, p<0.0001) were each found to correlate with higher HbA1c level,
      on analysis of a diabetes centre database in people under regular shared care.
      When combined, these biological variables strongly associate with the current
      HbA1c level.

PMID- 24582461
TI  - Cost-effectiveness analysis of extended duration anticoagulation with rivaroxaban
      to prevent recurrent venous thromboembolism.
AB  - INTRODUCTION: Extended duration anticoagulation with rivaroxaban for an
      additional 6-12 months can reduce recurrent venous thromboembolic events (VTE)
      compared to placebo by ~82%, but at the detriment of increased bleeding. We
      sought to estimate the cost-effectiveness of extended duration prophylaxis of
      recurrent VTE with rivaroxaban. MATERIAL AND METHODS: A Markov model was
      developed to estimate the cost-effectiveness of extended duration rivaroxaban,
      20mg daily, compared to placebo using a Medicare perspective, a one-monthcycle
      length and a 40-year time horizon. The model assumed a cohort of 58-year-old
      patients who had already completed an initial 6-12 months of anticoagulation with
      rivaroxaban or a vitamin K antagonist; and whom prescribers had clinical
      equipoise with respect to the need for continued anticoagulation. Data sources
      included EINSTEIN-Extension and other published studies of VTE. Outcomes included
      direct treatment costs (in 2013US$), quality-adjusted life-years (QALYs) and
      incremental cost-effectiveness ratios (ICERs). RESULTS: Extended duration
      rivaroxaban resulted in higher treatment costs ($22,645 vs. $22,083) but yielded
      greater QALYs (16.167 vs. 16.134) as compared to placebo; corresponding to an
      ICER of $17,030/QALY gained. Our model was most sensitive to the baseline risk of
      bleeding and recurrent VTE, the hazard ratio of developing a recurrent event
      while on rivaroxaban and time horizon. Monte Carlo Simulation suggested
      rivaroxaban would be cost-effective in 66% of 10,000 iterations, assuming a
      willingness-to-pay threshold of $50,000/QALY. CONCLUSION: Despite the cost of
      rivaroxaban and an increased risk of bleeding, extending VTE treatment for an
      additional 6-12 months with rivaroxaban was found cost-effective compared to the
      placebo over a 40-year time horizon.

PMID- 24582462
TI  - Differences in thrombus structure and kinetics in patients with type 2 diabetes
      mellitus after non ST elevation acute coronary syndrome.
AB  - INTRODUCTION: Despite optimal secondary prevention therapy following non-ST
      elevation acute coronary syndrome (NSTE-ACS), recurrent thrombotic events are
      more frequent in patients with type 2 diabetes mellitus (T2DM). MATERIALS AND
      METHODS: This exploratory study was aimed to evaluate quantitative and
      qualitative aspects of thrombus. In 28 patients with and without T2DM treated
      with aspirin and clopidogrel we assessed thrombus quantity using an ex-vivo
      chamber, platelet reactivity, thrombus ultrastructure and thrombus kinetics one
      week after NSTE-ACS. RESULTS: T2DM was associated with increased thrombus [14861
      (8003 to 30161) vs 8908 (6812 to 11996), MU(2)/mm, median (IQR), p=0.045] and
      platelet reactivity. In addition, diabetic thrombus showed lower visco-elastic
      tensile strength [(-0.2(-1.7 to 0.7) vs 1.0(-0.9 to 3.3), p=0.044)] and was more
      resistant to autolysis [(27.8(11.7 to 70.7) vs 78.8(68.5 to109.6) mm/min,
      p=0.002)]. On SEM, fibrin fibres in diabetes were thinner, with higher lateral
      interlinkage and mesh-like organisation. Thrombus quantity correlated inversely
      with thrombus retraction (r=-0.450 p=0.016) but not with platelet reactivity
      (r=0.153, p=0.544). CONCLUSIONS: Despite optimal antiplatelet therapy, T2DM
      patients after NSTE-ACS developed increased thrombus of lower tensile strength
      and slower retraction. SEM revealed loosely arranged fibrin fibres. Our data
      showed significant differences in the magnitude as well as structural and
      mechanistic characteristics of thrombus in patients with T2DM.

PMID- 24582463
TI  - Monoterpene glycosides, phenylpropanoids, and acacetin glycosides from
      Dracocephalum foetidum.
AB  - Chemical investigation of the acetone extract from the aerial parts of the
      Mongolian medicinal plant Dracocephalum foetidum resulted in the isolation of
      three limonene glycosides, a caffeic acid trimer, four rosmarinic acid
      glucosides, and five acacetin acyl glycosides, together with 13 known natural
      products. The chemical structures of all of the compounds were determined by
      spectroscopic analyses. Among these compounds three showed hyaluronidase
      inhibitory activity. In addition, one other compound showed stronger 1,1-diphenyl
      2-picrylhydrazyl radical scavenging activity than the positive control Trolox,
      whereas three other compounds demonstrated a similar activity to that of Trolox. 

PMID- 24582464
TI  - Threshold of galactomannan antigenemia positivity for early diagnosis of invasive
      aspergillosis in neutropenic children.
AB  - PURPOSE: Invasive aspergillosis (IA) is an important cause of morbidity and
      mortality in immunocompromised patients. Pediatric data on the accuracy and
      optimal cutoff of galactomannan antigen detection to diagnose IA is sparse and
      controversial. We evaluated the utility and optimal serum galactomannan assay
      (GA) cutoff in children. METHODS: Children with febrile neutropenia due to
      malignancy, hematopoietic stem cell transplant, aplastic anemia, or congenital
      neutropenia, were prospectively included from 2007 to 2011. All new episodes of
      febrile neutropenia were recorded. In case of a previous diagnosis of IA,
      subsequent episodes were excluded. One to four GA were tested by enzyme
      immunoassay during each episode. Bronchoalveolar lavage and other relevant
      samples for mycological diagnosis, and computed tomography of chest/sinus were
      performed wherever appropriate. IA was classified as "proven", "probable", and
      "possible" as per the 2008 European Organisation for Research and Treatment of
      Cancer and Mycoses Study Group Guidelines. The optimal cutoff value was
      determined using receiver operating characteristic curves in episode-wise
      analysis. RESULTS: There were 145 patients with 211 febrile episodes included:
      hematopoietic stem cell transplant (n = 15), oncological (n = 113), and
      hematological disorders (n = 17). Forty-five children (31.0%) developed IA (5
      proven, 15 probable, and 25 possible). Cutoff value of single GA >= 0.7 for
      proven/probable/possible IA offered the best combination of sensitivity
      (82.2%)/specificity (82.5%), and 94.4% negative predictive value. Two consecutive
      positive GA >= 0.7 had a sensitivity/specificity of 75.0%/91.0%. Index GA >= 1.9
      was associated with significantly higher mortality in children with IA and
      overall. CONCLUSION: Serum GA is sensitive to diagnose IA in pediatric patients
      with excellent negative predictive value at an optimal cutoff of >=0.7.
      Considering two consecutive values >=0.7 increases specificity to 91.0%.

PMID- 24582465
TI  - Investigations of kanuka and manuka essential oils for in vitro treatment of
      disease and cellular inflammation caused by infectious microorganisms.
AB  - BACKGROUND: Diseases caused by infectious and inflammatory microorganisms are
      among the most common and most severe nosocomial diseases worldwide. Therefore,
      developing effective agents for treating these illnesses is critical. In this
      study, essential oils from two tea tree species, kanuka (Kunzea ericoides) and
      manuka (Leptospermum scoparium), were evaluated for use in treating diseases and
      inflammation caused by microorganism infection. METHODS: Isolates of clinically
      common bacteria and fungi were obtained from American Type Culture Collection and
      from Kaohsiung Veterans General Hospital. Minimum inhibitory concentrations for
      Trichosporon mucoides, Malassezia furfur, Candida albicans, and Candida
      tropicalis were determined by the broth microdilution method with Sabouraud
      dextrose broth. The antibacterial susceptibility of Staphylococcus aureus,
      Streptococcus sobrinus, Streptococcus mutans, and Escherichia coli were
      determined by the broth microdilution method. A human acute monocytic leukemia
      cell line (THP-1) was cultured to test the effects of the essential oils on the
      release of the two inflammatory cytokines, tumor necrosis factor-alpha and
      interleukin-4. RESULTS: Multiple analyses of microorganism growth confirmed that
      both essential oils significantly inhibited four fungi and the four bacteria. The
      potent fungicidal properties of the oils were confirmed by minimum inhibitory
      concentrations ranging from 0.78% to 3.13%. The oils also showed excellent
      bactericidal qualities with 100% inhibition of the examined bacteria. In THP-1
      cells, both oils lowered tumor necrosis factor-alpha released after
      lipopolysaccharide stimulation. Finally, the antimicrobial and anti-inflammatory
      effects of the oils were obtained without adversely affecting the immune system.
      CONCLUSION: These results indicate that the potent antimicroorganism and anti
      inflammation properties of kanuka and manuka essential oils make them strong
      candidates for use in treating infections and immune-related disease. The data
      confirm the potential use of kanuka and manuka extracts as pharmaceutical
      antibiotics, medical cosmetology agents, and food supplements.

PMID- 24582466
TI  - Change in convergence and accommodation after two weeks of eye exercises in
      typical young adults.
AB  - BACKGROUND: Although eye exercises appear to help heterophoria, convergence
      insufficiency, and intermittent strabismus, results can be confounded by placebo,
      practice, and encouragement effects. This study assessed objective changes in
      vergence and accommodation responses in naive young adults after a 2-week period
      of eye exercises under controlled conditions to determine the extent to which
      treatment effects occur over other factors. METHODS: Asymptomatic young adults
      were randomly assigned to one of two no-treatment (control) groups or to one of
      six eye exercise groups: accommodation, vergence, both, convergence in excess of
      accommodation, accommodation in excess of convergence, and placebo. Subjects were
      tested and retested under identical conditions, except for the second control
      group, who were additionally encouraged. Objective accommodation and vergence
      were assessed to a range of targets moving in depth containing combinations of
      blur, disparity, and proximity/looming cues. RESULTS: A total of 156 subjects
      were included. Response gain improved more for less naturalistic targets where
      more improvement was possible. Convergence exercises improved vergence for near
      across all targets (P = 0.035). Mean accommodation changed similarly but
      nonsignificantly. No other treatment group differed significantly from the
      nonencouraged control group, whereas encouraging effort produced significantly
      increased vergence (P = 0.004) and accommodation (P = 0.005) gains in the second
      control group. CONCLUSIONS: True treatment effects were small, significantly
      better only after vergence exercises to a nonaccommodative target, and rarely
      related to the response they were designed to improve. Exercising accommodation
      without convergence made no difference to accommodation to cues containing
      detail. Additional effort improved objective responses the most.

PMID- 24582467
TI  - Herpes zoster ophthalmicus with isolated trochlear nerve palsy in an otherwise
      healthy 13-year-old girl.
AB  - Herpes zoster ophthalmicus is rare in healthy children. It is occasionally
      associated with extraocular muscle palsies and rarely with isolated trochlear
      nerve palsy. We report a case of unilateral isolated trochlear nerve palsy
      associated with herpes zoster ophthalmicus in an immunocompetent 13-year-old girl
      who presented with diplopia and blurred vision in her right eye. The right cornea
      had multiple subepithelial opacities. Ocular motility returned to normal and
      diplopia and corneal opacification resolved with steroid therapy. To our
      knowledge, this is the first such case involving the troclear nerve in a child. 

PMID- 24582468
TI  - Evolution of isoprene emission capacity in plants.
AB  - Light-dependent de novo volatile isoprene emission by terrestrial plants
      (approximately 2% of carbon fixed during photosynthesis) contributes as much as
      0.5 PgC/year to the global carbon cycle. Although most plant taxa exhibit either
      constitutive or inducible monoterpene emissions, the evolution of isoprene
      emission capacity in multiple lineages has remained unexplained. Based on the
      predominant occurrence of isoprene emission capacity in long-lived, fast-growing
      woody plants; the relationship between 'metabolic scope' of tree genera and their
      species richness; and the proposed role of high growth rates and long generation
      times in accelerating molecular evolution, we hypothesise that long-lived plant
      genera with inherently high speciation rates have repeatedly acquired and lost
      the capacity to emit isoprene in their evolutionary history. 

PMID- 24582469
TI  - Within-session repeated a-tDCS: the effects of repetition rate and inter-stimulus
      interval on corticospinal excitability and motor performance.
AB  - OBJECTIVE: This study investigated the effect of rate and stimulation interval of
      anodal transcranial direct current stimulation (a-tDCS) on CSE and motor
      performance. METHODS: Twelve healthy individuals participated in this study. CSE
      was assessed before and after five experimental conditions of one, two or three
      applications of 10 min of a-tDCS with an interval of 5 or 25 min. a-tDCS was
      applied with a constant current density of 0.016 mA/cm(2). Purdue pegboard-test
      was selected for motor performance assessment. RESULTS: Compared to single 10 min
      stimulation, the magnitude of the within-session repeated a-tDCS induced
      excitability was enhanced significantly after the second stimulation was
      performed with an interval of 25 min, but not 5 min. However, by increasing the
      number of a-tDCS to three repetitions the CSE was significantly increased and
      lasted for 2h with both 5 and 25 min intervals. Furthermore, CSE enhancement
      remained significant for up to 24h for within session a-tDCS repetitions with 25
      min intervals. Likewise, significant improvement was seen in motor performance
      following three times repetition with 25 min inter-stimulus intervals.
      CONCLUSIONS: The results suggest that within session repeated a-tDCS with longer
      intervals within the lasting effects of the previous stimulations are preferable
      for increasing induced excitability changes with longer lasting effects.
      SIGNIFICANCE: It is of particular importance to increase the a-tDCS lasting
      effects to consolidate the neuroplastic CSE changes.

PMID- 24582470
TI  - High-calorie diets in amyotrophic lateral sclerosis.

PMID- 24582472
TI  - Calciphylaxis.

PMID- 24582471
TI  - Hypercaloric enteral nutrition in patients with amyotrophic lateral sclerosis: a
      randomised, double-blind, placebo-controlled phase 2 trial.
AB  - BACKGROUND: Amyotrophic lateral sclerosis is a fatal neurodegenerative disease
      with few therapeutic options. Mild obesity is associated with greater survival in
      patients with the disease, and calorie-dense diets increased survival in a mouse
      model. We aimed to assess the safety and tolerability of two hypercaloric diets
      in patients with amyotrophic lateral sclerosis receiving enteral nutrition.
      METHODS: In this double-blind, placebo-controlled, randomised phase 2 clinical
      trial, we enrolled adults with amyotrophic lateral sclerosis from participating
      centres in the USA. Eligible participants were aged 18 years or older with no
      history of diabetes or liver or cardiovascular disease, and who were already
      receiving percutaneous enteral nutrition. We randomly assigned participants
      (1:1:1) using a computer-generated list of random numbers to one of three dietary
      interventions: replacement calories using an isocaloric tube-fed diet (control),
      a high-carbohydrate hypercaloric tube-fed diet (HC/HC), or a high-fat
      hypercaloric tube-fed diet (HF/HC). Participants received the intervention diets
      for 4 months and were followed up for 5 months. The primary outcomes were safety
      and tolerability, analysed in all patients who began their study diet. This trial
      is registered with ClinicalTrials.gov, number NCT00983983. FINDINGS: Between Dec
      14, 2009, and Nov 2, 2012, we enrolled 24 participants, of whom 20 started their
      study diet (six in the control group, eight in the HC/HC group, and six in the
      HF/HC group). One patient in the control group, one in the HC/HC group, and two
      in the HF/HC group withdrew consent before receiving the intervention.
      Participants who received the HC/HC diet had a smaller total number of adverse
      events than did those in the other groups (23 in the HC/HC group vs 42 in the
      control group vs 48 in the HF/HC group; overall, p=0.06; HC/HC vs control,
      p=0.06) and significantly fewer serious adverse events than did those on the
      control diet (none vs nine; p=0.0005). Fewer patients in the HC/HC group
      discontinued their study diet due to adverse events (none [0%] of eight in the
      HC/HC group vs three [50%] of six in the control group). During the 5 month
      follow-up, no deaths occurred in the nine patients assigned to the HC/HC diet
      compared with three deaths (43%) in the seven patients assigned to the control
      diet (log-rank p=0.03). Adverse events, tolerability, deaths, and disease
      progression did not differ significantly between the HF/HC group and the control
      group. INTERPRETATION: Our results provide preliminary evidence that hypercaloric
      enteral nutrition is safe and tolerable in patients with amyotrophic lateral
      sclerosis, and support the study of nutritional interventions in larger
      randomised controlled trials at earlier stages of the disease. FUNDING: Muscular
      Dystrophy Association, National Center for Research Resources, National
      Institutes of Health, and Harvard NeuroDiscovery Center.

PMID- 24582473
TI  - A classification model of patient engagement methods and assessment of their
      feasibility in real-world settings.
AB  - OBJECTIVE: Examine existing reviews of patient engagement methods to propose a
      model where the focus is on engaging patients in clinical workflows, and to
      assess the feasibility of advocated patient engagement methods. METHODS: A
      literature search of reviews of patient engagement methods was conducted.
      Included reviews were peer-reviewed, written in English, and focused on methods
      that targeted patients or patient-provider dyads. Methods were categorized to
      propose a conceptual model. The feasibility of methods was assessed using an
      adapted rating system. RESULTS: We observed that we could categorize patient
      engagement methods based on information provision, patient activation, and
      patient-provider collaboration. Methods could be divided by high and low
      feasibility, predicated on the extent of extra work required by the patient or
      clinical system. Methods that have good fit with existing workflows and that
      require proportional amounts of work by patients are likely to be the most
      feasible. CONCLUSION: Implementation of patient engagement methods is likely to
      depend on finding a "sweet-spot" where demands required by patients generate
      improved knowledge and motivate active participation. PRACTICE IMPLICATIONS:
      Attention should be given to those interventions and methods that advocate
      feasibility with patients, providers, and organizational workflows.

PMID- 24582474
TI  - The assessment and treatment of postural disorders in cerebellar ataxia: a
      systematic review.
AB  - Gait and balance disorders are often major causes of handicap in patients with
      cerebellar ataxia. Although it was thought that postural and balance disorders in
      cerebellar ataxia were not treatable, recent studies have demonstrated the
      beneficial effects of rehabilitation programs. This article is the first
      systematic review on the treatment of postural disorders in cerebellar ataxia.
      Nineteen articles were selected, of which three were randomized, controlled
      trials. Various aetiologies of cerebellar ataxia were studied: five studies
      assessed patients with multiple sclerosis, four assessed patients with
      degenerative ataxia, two assessed stroke patients and eight assessed patients
      with various aetiologies. Accurate assessment of postural disorders in cerebellar
      ataxia is very important in both clinical trials and clinical practice. The Scale
      for the Assessment and Rating of Ataxia (SARA) is a simple, validated measurement
      tool, for which 18 of the 40 points are related to postural disorders. This scale
      is useful for monitoring ataxic patients with postural disorders. There is now
      moderate level evidence that rehabilitation is efficient to improve postural
      capacities of patients with cerebellar ataxia - particularly in patients with
      degenerative ataxia or multiple sclerosis. Intensive rehabilitation programs with
      balance and coordination exercises are necessary. Although techniques such as
      virtual reality, biofeedback, treadmill exercises with supported bodyweight and
      torso weighting appear to be of value, their specific efficacy has to be further
      investigated. Drugs have only been studied in degenerative ataxia, and the level
      of evidence is low. There is now a need for large, randomized, controlled trials
      testing rehabilitation programs suited to postural and gait disorders of patients
      with cerebellar ataxia.

PMID- 24582475
TI  - Anti-myelin oligodendrocyte glycoprotein (MOG) antibodies in a Japanese boy with
      recurrent optic neuritis.
AB  - BACKGROUND: Myelin oligodendrocyte glycoprotein (MOG) localizes on the outermost
      surface of the myelin sheath and oligodendrocytes in the central nervous system
      (CNS). Autoantibodies against MOG are reportedly found in patients with spectrum
      of inflammatory demyelinating diseases of the CNS, including acute disseminated
      encephalomyelitis, multiple sclerosis, and neuromyelitis optica. In addition,
      recent studies have emphasized an association between anti-MOG antibodies and
      optic neuritis. PATIENT: We present the first case report of a 7-year-old
      Japanese boy who was positive for anti-MOG antibodies. He experienced four
      episodes of unilateral optic neuritis and one seizure event. Magnetic resonance
      imaging revealed T2-hyperintense lesions in the subcortical white matter and
      midbrain. Although he fulfilled the diagnostic criteria for multiple sclerosis,
      recombinant interferon beta did not prevent recurrence. Established cell-based
      immunoassays revealed that he was positive for anti-MOG antibodies and negative
      for anti-aquaporin 4 antibodies. CONCLUSIONS: Our case report supports the
      relationship between anti-MOG antibodies and recurrent optic neuritis. Additional
      studies are needed to establish the clinical significance of anti-MOG antibodies
      for diagnosis, treatment, and prognosis.

PMID- 24582476
TI  - cis-1-Oxo-heterocyclyl-4-amido cyclohexane derivatives as NPY5 receptor
      antagonists.
AB  - The NPY5 receptor binding and pharmacokinetic properties of a novel series of cis
      1-oxo-heterocyclyl-4-amido-cyclohexane derivatives are described. 

PMID- 24582477
TI  - Synthesis and evaluation of a novel class Hsp90 inhibitors containing 1
      phenylpiperazine scaffold.
AB  - Previously, we identified 1-(2-(4-bromophenoxy)ethoxy)-3-(4-(2
      methoxyphenyl)piperazin-1-yl)propan-2-ol (1) as a novel Hsp90 inhibitor with
      moderate activity through virtual screening. In this study, we report the
      optimization process of 1. A series of analogues containing the 1
      phenylpiperazine core scaffold were synthesized and evaluated. The structure
      activity relationships (SAR) for these compounds was also discussed for further
      molecular design. This effort afforded the most active inhibitor 13f with
      improved activity in not only target-based level, but also cell-based level
      compared with the original hit 1. 

PMID- 24582478
TI  - Synthesis of ethynylbenzene-substituted glycol as a versatile probe for labeling
      oligonucleotides.
AB  - Positron emission tomography (PET) is a highly sensitive quantitative imaging
      technique for studying molecular pathways and interactions in vivo. This imaging
      technique plays a key role in drug discovery, pharmacokinetics, pharmacodynamics,
      and assessing in vivo distribution. In this study, we designed an ethynylbenzene
      substituted glycol (M(E)) as a versatile probe for PET labeling of
      oligonucleotides through a click reaction. 

PMID- 24582480
TI  - Comparison of radiocarbon techniques for the assessment of biobase content in
      fuels.
AB  - A comparison was made between various radiocarbon measurement techniques for the
      purpose of quantifying each methods capability for the proper apportionment of
      biobase-derived additives to gasoline. Measurement techniques include (1) direct
      liquid scintillation counting, (2) carbon dioxide absorption followed by liquid
      scintillation counting, (3) conversion to benzene followed by liquid
      scintillation counting and (4) accelerator mass spectrometry. In addition, stable
      isotope ratios of carbon and hydrogen were determined to assist in the
      authentication of a fuels source with regard to petrochemical or biobase origin
      is required for the confirmation of minimum anti-knock components, consumer
      awareness and proper assessment for regulatory taxation. Accelerator mass
      spectrometry was found to be the most precise technique followed by conversion of
      fuel to benzene with liquid scintillation counting and direct counting by liquid
      scintillation counting. Finally, liquid scintillation counting of absorbed carbon
      dioxide was found to be the least precise and should not be used for this
      analysis. The high to low precisions correlate with the high to low cost of
      equipment and support required by each of these methods except for direct liquid
      scintillation counting. Therefore, laboratories interested in developing
      capability to perform such authentication can use this data to consider the
      economics of the optimum technique to use for radiocarbon measurement. 

PMID- 24582479
TI  - Novel dimeric Smac analogs as prospective anticancer agents.
AB  - A small library of monovalent Smac mimics with general structure NMeAla-Tle-(4R)
      4-Benzyl-Pro-Xaa-cysteamide, was synthesized (Xaa=hydrophobic residue). The
      library was screened in vitro against human breast cancer cell lines MCF-7 and
      MDA-MB-231, and two most active compounds oligomerized via S-alkylation giving
      bivalent and trivalent derivatives. The most active bivalent analogue SMAC17-2X
      was tested in vivo and in physiological conditions (mouse model) it exerted a
      potent anticancer effect resulting in ~23.4days of tumor growth delay at 7.5mg/kg
      dose. Collectively, our findings suggest that bivalent Smac analogs obtained via
      S-alkylation protocol may be a suitable platform for the development of new
      anticancer therapeutics. 

PMID- 24582481
TI  - Enhanced activities of organically bound tritium in biota samples.
AB  - A pilot study aimed on possible occurrence of elevated activity of non
      exchangable organically bound tritium (NE-OBT) in biota was performed. The first
      results showed a significant surplus of NE-OBT activity in biota of the valley of
      Mohelno reservoir and Jihlava river. The liquid releases of HTO from the nuclear
      power plant Dukovany is the source of tritium in this area. This area can be a
      source of various types of natural samples for future studies of tritium
      pathways. 

PMID- 24582482
TI  - Birth weight and subsequent risk of asthma: a systematic review and meta
      analysis.
AB  - BACKGROUND: Previous studies suggest that birth weight is related to later risk
      of asthma. However, few meta-analyses have investigated these associations.
      Therefore, we performed a meta-analysis with different classifications to further
      validate the relationship between birth weight and asthma. METHODS: PubMed (1990
      2013), ScienceDirect (1990-2013), EMBASE(1990-2013),EBSCO (1990-2013) and
      Springer (1990-2013) were searched for articles. The following MeSH terms were
      used: "birth weight", "fetal growth retardation", "intrauterine growth
      restriction", "asthma", "wheezing". RESULTS: We included 18 studies with data
      from a total of over 90,000 children and adults. (1) Low birth weight (<2,500g)
      as compared with BW>2,500g and BW=2500-4000g was associated with increased risk
      of asthma (Children: OR, 1.28; 95% CI, 1.09-1.50, P<0.05; OR, 1.34; 95% CI, 1.13
      1.60, P<0.05, Adults: OR, 1.25; 95% CI, 1.12-1.39, P<0.05; OR, 1.25; 95% CI, 1.12
      1.40, P<0.05). (2) High birth weight (>4,000g) was not associated with the risk
      of asthma when BW<4,000g and BW=2500-4000g were used as the reference.
      CONCLUSIONS: These results suggest that low birth weight (<2,500g) is associated
      with increased risk of asthma both in children and adults and may serve as a
      mediator between prenatal influences and later disease risk; but high birth
      weight (>4,000g) was not associated with increased risk of asthma.

PMID- 24582484
TI  - Maternal influenza vaccine and risks for preterm or small for gestational age
      birth.
AB  - OBJECTIVE: To study the impact of influenza vaccine administered to pregnant
      women during all trimesters on the rates of preterm and small for gestational age
      (SGA) births, evaluating both increased and decreased risk. STUDY DESIGN: This
      retrospective observational matched cohort study involved 7 Vaccine Safety
      Datalink sites across the US for the 2004-05 through 2008-09 influenza seasons.
      Cohort eligibility and outcomes were determined from administrative, claims,
      medical records, and birth data. In propensity score- and vaccine exposure time
      matched analyses, ORs for preterm and SGA births were calculated. RESULTS: Among
      57 554 matched vaccinated and unvaccinated pregnant women, including 16 240 women
      in the first trimester, maternal vaccination was not associated with increased or
      decreased risk for preterm birth (OR for delivery at <37 weeks gestation, 0.97
      [95% CI, 0.93-1.02]; for delivery at <=32 weeks gestation, 0.98 [95% CI, 0.86
      1.12]; and for delivery at <=34 weeks gestation, 0.96 [95% CI, 0.88-1.04]) or SGA
      birth (OR for <5th percentile weight for gestational age, 1.02 [95% CI, 0.96
      1.09], and for <10th percentile weight for gestational age, 1.00 [95% CI, 0.96
      1.04]). Similarly, first trimester vaccination was not associated with increased
      or decreased risk for preterm or SGA birth. CONCLUSION: Receipt of trivalent
      inactivated influenza vaccine during pregnancy was not associated with increased
      or decreased risk of preterm or SGA birth. These findings support the safety of
      vaccinating pregnant women against influenza during the first, second, and third
      trimesters, and suggest that a nonspecific protective effect of the influenza
      vaccine for these outcomes does not exist.

PMID- 24582485
TI  - Quality of life as a primary endpoint in ovarian cancer trials.

PMID- 24582487
TI  - RTEL1: functions of a disease-associated helicase.
AB  - DNA secondary structures that arise during DNA replication, repair, and
      recombination (3R) must be processed correctly to prevent genetic instability.
      Regulator of telomere length 1 (RTEL1) is an essential DNA helicase that
      disassembles a variety of DNA secondary structures to facilitate 3R processes and
      to maintain telomere integrity. The past few years have witnessed the emergence
      of RTEL1 variants that confer increased susceptibility to high-grade glioma,
      astrocytomas, and glioblastomas. Mutations in RTEL1 have also been implicated in
      Hoyeraal-Hreidarsson syndrome, a severe form of the bone-marrow failure and
      cancer predisposition disorder, dyskeratosis congenita. We review these recent
      findings and highlight its crucial link between DNA secondary-structure
      metabolism and human disease. 

PMID- 24582483
TI  - Longitudinal associations between sex, diabetes self-care, and health-related
      quality of life among youth with type 1 or type 2 diabetes mellitus.
AB  - OBJECTIVE: To examine the longitudinal associations between sex, diabetes self
      care, and the health-related quality of life (HRQL) of children and adolescents
      with type 1 or type 2 diabetes. STUDY DESIGN: The sample included 910
      participants with type 1 and 241 participants with type 2, ages 10-22 years at
      baseline, from the SEARCH for Diabetes in Youth Study, a longitudinal
      observational study. The primary outcome measure was the Pediatric Quality of
      Life Inventory. Repeated measures, mixed-model regression analysis was conducted
      with the use of data from baseline and at least one follow-up assessment,
      spanning approximately 4 years. RESULTS: HRQL was greater among those with type 1
      versus type 2 diabetes. Among participants with type 1, greater (better)
      Pediatric Quality of Life Inventory total scores over time were related to
      greater parent education (P = .0007), lower glycated hemoglobin values (P <
      .0001), and greater physical activity during the past 7 days (P = .0001). There
      was a significant interaction between sex and age (P < .0001); girls' HRQL
      remained stable or decreased over time, whereas males' HRQL increased. For
      participants with type 2 diabetes, there was no significant interaction by age
      and sex, but lower total HRQL was related to being female (P = .011) and greater
      body mass index z-scores (P = .014). CONCLUSIONS: HRQL in this cohort varied by
      diabetes type. The interaction between sex and age for type 1 participants,
      coupled with poorer HRQL among female than male participants with type 2
      diabetes, suggests the impacts of diabetes on HRQL differ by sex and should be
      considered in clinical management. Encouraging physical activity and weight
      control continue to be important in improving HRQL.

PMID- 24582488
TI  - Increased lysophospholipase D activity of autotaxin in sera of patients with
      atopic dermatitis.

PMID- 24582486
TI  - Carboplatin plus paclitaxel once a week versus every 3 weeks in patients with
      advanced ovarian cancer (MITO-7): a randomised, multicentre, open-label, phase 3
      trial.
AB  - BACKGROUND: Carboplatin plus paclitaxel administered every 3 weeks is standard
      first-line chemotherapy for patients with advanced ovarian cancer. A weekly
      paclitaxel schedule combined with carboplatin every 3 weeks prolonged progression
      free survival and overall survival in a Japanese phase 3 trial. The aim of our
      study was to assess whether a weekly schedule of carboplatin plus paclitaxel is
      more effective than the same drugs given every 3 weeks. METHODS: We did a
      multicentre, randomised, phase 3 study at 67 institutions in Italy and France.
      Women with FIGO stage IC-IV ovarian cancer, an ECOG performance status of 2 or
      lower, and who had never received chemotherapy were randomly allocated in a 1:1
      ratio to receive either carboplatin (AUC 6 mg/mL per min) plus paclitaxel (175
      mg/m(2)) every 3 weeks for six cycles or carboplatin (AUC 2 mg/mL per min) plus
      paclitaxel (60 mg/m(2)) every week for 18 weeks. Randomisation was done by
      computer-based minimisation, stratified by centre, residual disease after
      surgery, and ECOG performance status. The study was not blinded. Coprimary
      endpoints were progression-free survival and quality of life (assessed by the
      Functional Assessment of Cancer Therapy Ovarian Trial Outcome Index [FACT-O/TOI]
      score), and analysis was by modified intention to treat. This report presents the
      final analysis. The study is registered with ClinicalTrials.gov, number
      NCT00660842. FINDINGS: 822 patients were enrolled into the study between Nov 20,
      2008, and March 1, 2012; 12 withdrew their consent immediately after
      randomisation and were excluded, and 810 were eligible for analysis. 404 women
      were allocated treatment every 3 weeks and 406 were assigned to the weekly
      schedule. After median follow-up of 22.3 months (IQR 16.2-30.9), 449 progression
      free survival events were recorded. Median progression-free survival was 17.3
      months (95% CI 15.2-20.2) in patients assigned to treatment every 3 weeks, versus
      18.3 months (16.8-20.9) in women allocated to the weekly schedule (hazard ratio
      0.96, 95% CI 0.80-1.16; p=0.66). FACT-O/TOI scores differed significantly between
      the two schedules (treatment-by-time interaction p<0.0001); with treatment every
      3 weeks, FACT-O/TOI scores worsened at every cycle (weeks 1, 4, and 7), whereas
      for the weekly schedule, after transient worsening at week 1, FACT-O/TOI scores
      remained stable. Fewer patients assigned to the weekly group than those allocated
      treatment every 3 weeks had grade 3-4 neutropenia (167 [42%] of 399 patients vs
      200 [50%] of 400 patients), febrile neutropenia (two [0.5%] vs 11 [3%]), grade 3
      4 thrombocytopenia (four [1%] vs 27 [7%]), and grade 2 or worse neuropathy (24
      [6%] vs 68 [17%]). Three deaths during the study were attributed to chemotherapy;
      two women died who were allocated treatment every 3 weeks and one death was
      recorded in the group assigned the weekly regimen. INTERPRETATION: A weekly
      regimen of carboplatin and paclitaxel might be a reasonable option for first-line
      treatment of women with advanced ovarian cancer. FUNDING: None.

PMID- 24582489
TI  - Mental health care delivery system reform in Belgium: the challenge of achieving
      deinstitutionalisation whilst addressing fragmentation of care at the same time.
AB  - Most mental health care delivery systems in welfare states currently face two
      major issues: deinstitutionalisation and fragmentation of care. Belgium is in the
      process of reforming its mental health care delivery system with the aim of
      simultaneously strengthening community care and improving integration of care.
      The new policy model attempts to strike a balance between hospitals and community
      services, and is based on networks of services. We carried out a content analysis
      of the policy blueprint for the reform and performed an ex-ante evaluation of its
      plan of operation, based on the current knowledge of mental health service
      networks. When we examined the policy's multiple aims, intermediate goals,
      suggested tools, and their articulation, we found that it was unclear how the new
      policy could achieve its goals. Indeed, deinstitutionalisation and integration of
      care require different network structures, and different modes of governance.
      Furthermore, most of the mechanisms contained within the new policy were not
      sufficiently detailed. Consequently, three major threats to the effectiveness of
      the reform were identified. These were: issues concerning the relationship
      between network structure and purpose, the continued influence of hospitals
      despite the goal of deinstitutionalisation, and the heterogeneity in the actual
      implementation of the new policy. 

PMID- 24582490
TI  - Workplace exposure to engineered nanomaterials: the Italian path for the
      definition of occupational health and safety policies.
AB  - This study explores the way the publication of a National White Book on health
      and safety risks that affect workers in jobs involving Nanotechnologies and
      Nanomaterials influenced the key Italian stakeholders attitude toward this issue
      and identifies the standpoints and priorities shared among researchers and
      stakeholders to develop a policy framework to address this issue. The study not
      only highlights some important assumptions (i.e. the acknowledgment by the key
      stakeholders of the need for actions and the identification of objectives which
      can gain a wide consensus) for the establishment of a policy community that
      sustains the development of a policymaking process on the issue but, through the
      interaction between stakeholders and OSH researchers, it also identifies some in
      nuce proposals that represent the starting point for policy interventions aimed
      at meeting the needs of both stakeholders and scientific community. Results
      obtained in terms of clarification of interests at stake, identification of
      potential areas of consensus and level of key national actors' engagement
      achieved, show the potentialities of adopting a knowledge based and inclusive
      approach to policy-making to address the issue of prevention and management of
      health and safety risks related to technological innovation within a framework of
      scientific uncertainty. 

PMID- 24582491
TI  - Transient regional osteoporosis.
AB  - Transient regional osteoporosis (TRO) is a disease that predisposes to fragility
      fracture in weight bearing joints of mid-life women and men. Pregnant women may
      also suffer the process, usually at the hip. The prevalence of TRO is lower than
      the systemic form, associated with postmenopause and advanced age, but may be
      falsely diminished by under-diagnosis. The disease may be uni- or bilateral, and
      may migrate to distinct joints. One main feature of TRO is spontaneous recovery.
      Pain and progressive limitation in the functionality of the affected joint(s) are
      key symptoms. In the case of the form associated with pregnancy, difficulties in
      diagnosis derive from the relatively young age at presentation and from the
      clinical overlapping with the frequent aches during gestation. Densitometric
      osteoporosis in the affected region is not always present, but bone marrow edema,
      with or without joint effusion, is detected by magnetic resonance. There are not
      treatment guidelines, but the association of antiresorptives to symptomatic
      treatment seems to be beneficial. Surgery or other orthopedic interventions can
      be required for specific indications, like hip fracture, intra-medullary
      decompression, or other. 

PMID- 24582492
TI  - Resection of the primary pancreatic neuroendocrine tumor in patients with
      unresectable liver metastases: possible indications for a multimodal approach.
AB  - BACKGROUND: Pancreatic neuroendocrine tumors (PNETs) present in more than 50% of
      cases with liver metastases as the only systemic localization. Liver metastases
      are unresectable in 80% of cases at diagnosis. In the context of a metastatic
      disease, the benefit of primary tumor removal in terms of survival is
      controversial. METHODS: A single-center series of patients with PNETs presenting
      with synchronous unresectable hepatic metastases and treated within a framework
      of a multidisciplinary team was analyzed retrospectively to assess the prognostic
      factors and the potential benefit of primary tumor resection on long-term
      survival. RESULTS: At the time of diagnosis, 12 of 43 patients (28%) underwent
      primary tumor resection. After a median follow-up of 5 years (range, 0.6-14
      years), 22 disease-related deaths were observed. The corresponding 5-year
      survival and median disease-specific duration of survival were 58% and 77 months,
      respectively. In the operated and nonoperated patients the 5-year disease
      specific survival was 82% and 50%, respectively (P = .027). At multivariate
      analysis, patients with primary tumor removed had an improved survival compared
      with patients who did not (hazard ratio 0.18; 95% CI 0.05-0.66; P = .010). Other
      important factors associated with improved survival at multivariate analysis were
      lesser age, lesser Ki-67 index, and 25% less liver tumor burden. CONCLUSION: In
      the present series of patients with PNETs and unresectable liver metastases,
      resection of the primary tumor was associated with an improved survival. This
      observation suggests that resection of the primary tumor should be part of a
      global therapeutic strategy and its indication and timing should be discussed
      within a multidisciplinary team.

PMID- 24582493
TI  - Perianal implantation of bioengineered human internal anal sphincter constructs
      intrinsically innervated with human neural progenitor cells.
AB  - BACKGROUND: The internal anal sphincter (IAS) is a major contributing factor to
      pressure within the anal canal and is required for maintenance of rectoanal
      continence. IAS damage or weakening results in fecal incontinence. We have
      demonstrated that bioengineered, intrinsically innervated, human IAS tissue
      replacements possess key aspects of IAS physiology, such as the generation of
      spontaneous basal tone and contraction/relaxation in response to
      neurotransmitters. The objective of this study is to demonstrate the feasibility
      of implantation of bioengineered IAS constructs in the perianal region of athymic
      rats. METHODS: Human IAS tissue constructs were bioengineered from isolated human
      IAS circular smooth muscle cells and human enteric neuronal progenitor cells.
      After maturation of the bioengineered constructs in culture, they were implanted
      operatively into the perianal region of athymic rats. Platelet-derived growth
      factor was delivered to the implanted constructs through a microosmotic pump.
      Implanted constructs were retrieved from the animals 4 weeks postimplantation.
      RESULTS: Animals tolerated the implantation well, and there were no early
      postoperative complications. Normal stooling was observed during the implantation
      period. At harvest, implanted constructs were adherent to the perirectal rat
      tissue and appeared healthy and pink. Immunohistochemical analysis revealed
      neovascularization. Implanted smooth muscle cells maintained contractile
      phenotype. Bioengineered constructs responded in vitro in a tissue chamber to
      neuronally evoked relaxation in response to electrical field stimulation and
      vasoactive intestinal peptide, indicating the preservation of neuronal networks.
      CONCLUSION: Our results indicate that bioengineered innervated IAS constructs can
      be used to augment IAS function in an animal model. This is a regenerative
      medicine based therapy for fecal incontinence that would directly address the
      dysfunction of the IAS muscle.

PMID- 24582494
TI  - Abdominal rectus muscle atrophy and midline shift after colostomy creation.
AB  - INTRODUCTION: Incisional hernia (IH) can be attributed to multiple factors. The
      presence of a parastomal hernia has shown to be a risk factor for IH after
      midline laparotomy. Our hypothesis is that this increased risk of IH may be
      caused by changes in biomechanical forces, such as midline shift to the
      contralateral side of the colostomy owing to decreased restraining forces at the
      site of the colostomy, and left abdominal rectus muscle (ARM) atrophy owing to
      intercostal nerve damage. METHODS: Patients were selected if they underwent end
      colostomy via open operation between 2004 and 2011. Patients were eligible if
      computed tomography (CT) had been performed postoperatively. If available,
      preoperative CTs were collected for case-control analyses. Midline shift was
      measured using V-scope application in the I-space, a CAVE-like virtual reality
      system. For the ARM atrophy hypothesis, measurements of ARM were performed at the
      level of colostomy, and 3 and 8 cm cranial and caudal of the colostomy. RESULTS:
      Postoperative CT were available for 77 patients; of these patients, 30 also had a
      preoperative CT. Median follow-up was 19 months. A mean shift to the right side
      was identified after preoperative and postoperative comparison; from -1.3 +/- 4.6
      to 2.1 +/- 9.3 (P = .043). Furthermore, during rectus muscle measurements, a
      thinner left ARM was observed below the level of colostomy. DISCUSSION: Creation
      of a colostomy alters the abdominal wall. Atrophy of the left ARM was seen caudal
      to the level of the colostomy, and a midline shift to the right side was evident
      on CT. These changes may explain the increased rate of IH after colostomy
      creation.

PMID- 24582495
TI  - Blockage of CXCR2 suppresses tumor growth of intrahepatic cholangiocellular
      carcinoma.
AB  - BACKGROUND/AIMS: Complete operative resection is the only approach to cure for
      intrahepatic cholangiocellular carcinoma (ICC), but the disease's prognosis is
      notably poor. A novel therapeutic approach is urgently required. CXC chemokine
      receptor 2 (CXCR2) has been associated with tumorigenesis and metastasis in human
      cancers. In this study, we investigated the suppressive effect of ICC growth by
      blocking CXCR2. MATERIAL AND METHODS: The role of CXCR2 was estimated using the
      human ICC cell lines, RBE and SSP25. CXCR2 small interfering RNA (siRNA) and an
      antagonist (SB225002) were used to block CXCR2. Proliferation assays, migration
      assays, and invasion assays were performed to confirm the suppressive effect of
      blocking CXCR2. Subcutaneous SSP25 tumors were established in athymic nude mice,
      and the mice were given SB225002. The expression of CXCR2 in ICC was determined
      by immunohistochemical staining of 34 ICC specimens. We investigated the
      relationship between CXCR2 expression and prognosis in ICC. RESULTS: The
      prognosis of patients who had higher CXCR2 expression in ICC was significantly
      poor (P = .004). CXCR2 siRNA treatment significantly suppressed CXCR2 expression
      in both RBE and SSP25. Cell proliferation, migration, and invasion were
      significantly suppressed by both CXCR2 siRNA and SB225002 compared with the
      control group. SB225002 also suppressed the growth of transplanted subcutaneous
      tumors (P = .02) CONCLUSION: Our results demonstrated that blocking CXCR2 clearly
      suppressed the development of ICC. Blocking CXCR2 may be a promising therapeutic
      approach for ICC.

PMID- 24582496
TI  - Clinical significance of pretherapeutic Ki67 as a predictive parameter for
      response to neoadjuvant chemotherapy in breast cancer: is it equally useful
      across tumor subtypes?
AB  - BACKGROUND: Ki67 has been identified as a prognostic and predictive marker for
      breast cancer and it was suggested that it may contribute to pathologic complete
      response (pCR) after neoadjuvant chemotherapy. It is unclear whether expression
      of Ki67 is particularly helpful for prediction of pCR across tumor subtypes.
      METHODS: Pretherapeutic Ki67 was evaluated in a series of 121 breast cancer core
      biopsies. After neoadjuvant chemotherapy, we used postoperative specimens to
      evaluate the pCR status. Several parameters predictive of pCR were identified
      using logistic regression analysis. We investigated subgroups defined by estrogen
      receptor (ER), progesterone receptor, and human epidermal growth factor receptor
      2, in which predicting pCR with Ki67 might be feasible. RESULTS: Ki67 was found
      to be an independent predictor of pCR in multivariate analysis (odds ratio [OR],
      3.62; 95% CI, 1.21-10.8). When stratified by ER, the above significance was
      exclusive to ER-positive tumors (OR, 6.24; 95% CI, 1.40-27.7). Using an receiver
      operating characteristic curve, we obtained moderate discriminative accuracy with
      an area under the curve of 0.7752 for Ki67 prediction of pCR in ER-positive
      tumors. In subgroup analysis, patients with high Ki67 showed significantly
      improved pCR rate in luminal-type disease, with a median Ki67 value of 43% in the
      patients who achieved pCR, versus 29% for those without pCR (P = .018), whereas
      no associations were observed in other subtypes. CONCLUSION: Our results suggest
      that stratification according to Ki67 levels might improve predictive
      significance of the response in hormone-responsive breast cancer. Even in these
      subtypes assumed to be less chemosensitive, some patients with highly
      proliferative tumors derive a significant benefit from chemotherapy, and
      consequently it is important to identify them.

PMID- 24582497
TI  - The breast cancer oncogene EMSY represses transcription of antimetastatic
      microRNA miR-31.
AB  - Amplification of the EMSY gene in sporadic breast and ovarian cancers is a poor
      prognostic indicator. Although EMSY has been linked to transcriptional silencing,
      its mechanism of action is unknown. Here, we report that EMSY acts as an
      oncogene, causing the transformation of cells in vitro and potentiating tumor
      formation and metastatic features in vivo. We identify an inverse correlation
      between EMSY amplification and miR-31 expression, an antimetastatic microRNA, in
      the METABRIC cohort of human breast samples. Re-expression of miR-31 profoundly
      reduced cell migration, invasion, and colony-formation abilities of cells
      overexpressing EMSY or haboring EMSY amplification. We show that EMSY is
      recruited to the miR-31 promoter by the DNA binding factor ETS-1, and it
      represses miR-31 transcription by delivering the H3K4me3 demethylase JARID1b/PLU
      1/KDM5B. Altogether, these results suggest a pathway underlying the role of EMSY
      in breast cancer and uncover potential diagnostic and therapeutic targets in
      sporadic breast cancer.

PMID- 24582498
TI  - Assessing kinetics from fixed cells reveals activation of the mitotic entry
      network at the S/G2 transition.
AB  - During the cell cycle, DNA duplication in S phase must occur before a cell
      divides in mitosis. In the intervening G2 phase, mitotic inducers accumulate,
      which eventually leads to a switch-like rise in mitotic kinase activity that
      triggers mitotic entry. However, when and how activation of the signaling network
      that promotes the transition to mitosis occurs remains unclear. We have developed
      a system to reduce cell-cell variation and increase accuracy of fluorescence
      quantification in single cells. This allows us to use immunofluorescence of
      endogenous marker proteins to assess kinetics from fixed cells. We find that
      mitotic phosphorylations initially occur at the completion of S phase, showing
      that activation of the mitotic entry network does not depend on protein
      accumulation through G2. Our data show insights into how mitotic entry is linked
      to the completion of S phase and forms a quantitative resource for mathematical
      models of the human cell cycle.

PMID- 24582499
TI  - TAIL-seq: genome-wide determination of poly(A) tail length and 3' end
      modifications.
AB  - Global investigation of the 3' extremity of mRNA (3'-terminome), despite its
      importance in gene regulation, has not been feasible due to technical challenges
      associated with homopolymeric sequences and relative paucity of mRNA. We here
      develop a method, TAIL-seq, to sequence the very end of mRNA molecules. TAIL-seq
      allows us to measure poly(A) tail length at the genomic scale. Median poly(A)
      length is 50-100 nt in HeLa and NIH 3T3 cells. Poly(A) length correlates with
      mRNA half-life, but not with translational efficiency. Surprisingly, we discover
      widespread uridylation and guanylation at the downstream of poly(A) tail. The U
      tails are generally attached to short poly(A) tails (<25 nt), while the G tails
      are found mainly on longer poly(A) tails (>40 nt), implicating their generic
      roles in mRNA stability control. TAIL-seq is a potent tool to dissect dynamic
      control of mRNA turnover and translational control, and to discover unforeseen
      features of RNA cleavage and tailing. 

PMID- 24582500
TI  - Phosphorylation of LSD1 by PKCalpha is crucial for circadian rhythmicity and
      phase resetting.
AB  - The circadian clock is a self-sustaining oscillator that controls daily rhythms.
      For the proper circadian gene expression, dynamic changes in chromatin structure
      are important. Although chromatin modifiers have been shown to play a role in
      circadian gene expression, the in vivo role of circadian signal-modulated
      chromatin modifiers at an organism level remains to be elucidated. Here, we
      provide evidence that the lysine-specific demethylase 1 (LSD1) is phosphorylated
      by protein kinase Calpha (PKCalpha) in a circadian manner and the phosphorylated
      LSD1 forms a complex with CLOCK:BMAL1 to facilitate E-box-mediated
      transcriptional activation. Knockin mice bearing phosphorylation-defective
      Lsd1(SA/SA) alleles exhibited altered circadian rhythms in locomotor behavior
      with attenuation of rhythmic expression of core clock genes and impaired phase
      resetting of circadian clock. These data demonstrate that LSD1 is a key component
      of the molecular circadian oscillator, which plays a pivotal role in rhythmicity
      and phase resetting of the circadian clock. 

PMID- 24582501
TI  - Uncovering SUMOylation dynamics during cell-cycle progression reveals FoxM1 as a
      key mitotic SUMO target protein.
AB  - Loss of small ubiquitin-like modification (SUMOylation) in mice causes genomic
      instability due to the missegregation of chromosomes. Currently, little is known
      about the identity of relevant SUMO target proteins that are involved in this
      process and about global SUMOylation dynamics during cell-cycle progression. We
      performed a large-scale quantitative proteomics screen to address this and
      identified 593 proteins to be SUMO-2 modified, including the Forkhead box
      transcription factor M1 (FoxM1), a key regulator of cell-cycle progression and
      chromosome segregation. SUMOylation of FoxM1 peaks during G2 and M phase, when
      FoxM1 transcriptional activity is required. We found that a SUMOylation-deficient
      FoxM1 mutant was less active compared to wild-type FoxM1, implying that
      SUMOylation of the protein enhances its transcriptional activity.
      Mechanistically, SUMOylation blocks the dimerization of FoxM1, thereby relieving
      FoxM1 autorepression. Cells deficient for FoxM1 SUMOylation showed increased
      levels of polyploidy. Our findings contribute to understanding the role of
      SUMOylation during cell-cycle progression. 

PMID- 24582504
TI  - Evaluating reliable and clinically significant change in eating disorders:
      comparisons to changes in DSM-IV diagnoses.
AB  - Assessing clinically meaningful change is valuable for treatment planning,
      monitoring course of illness and evaluating outcome. Although DSM eating disorder
      (ED) diagnoses have been criticized for poor clinical utility, instability, and
      uncertainty, remission/change of diagnosis is often the standard for evaluating
      outcome. We tested the validity of the clinically significant reliable change
      index (CS/RCI) compared to change in DSM-IV ED-diagnoses. We investigated if
      CS/RCI was concordant to diagnostic change and compared explained variance on
      measures at follow-up. Using a database for specialized ED treatment in Sweden
      the sample contained 1042 female patients (246 adolescents/796 adults). CS/RCI
      was calculated for the Clinical Impairment Assessment (CIA) and the Eating
      Disorder Examination Questionnaire (EDE-Q). CS/RCI explained more variance in
      gain scores for psychopathology measures than diagnostic change (DSM-IV). Average
      agreement between diagnostic change and CS/RCI was 62% and 60% for CIA and EDE-Q,
      respectively. Diagnostic change always resulted in more positive outcome than
      CS/RCI. Together with clinical judgment, CS/RCI is a valuable method for
      determining clinically significant changes in clinical practice and research. It
      is economically sound and results are easily interpreted and communicated to
      patients. 

PMID- 24582503
TI  - The effect of service satisfaction and spiritual well-being on the quality of
      life of patients with schizophrenia.
AB  - Quality of life (QOL) has been considered an important outcome measure in
      psychiatric research and determinants of QOL have been widely investigated. We
      aimed at detecting predictors of QOL at baseline and at testing the longitudinal
      interrelations of the baseline predictors with QOL scores at a 1-year follow-up
      in a sample of patients living in Residential Facilities (RFs). Logistic
      regression models were adopted to evaluate the association between WHOQoL-Bref
      scores and potential determinants of QOL. In addition, all variables
      significantly associated with QOL domains in the final logistic regression model
      were included by using the Structural Equation Modeling (SEM). We included 139
      patients with a diagnosis of schizophrenia spectrum. In the final logistic
      regression model level of activity, social support, age, service satisfaction,
      spiritual well-being and symptoms' severity were identified as predictors of QOL
      scores at baseline. Longitudinal analyses carried out by SEM showed that 40% of
      QOL follow-up variability was explained by QOL at baseline, and significant
      indirect effects toward QOL at follow-up were found for satisfaction with
      services and for social support. Rehabilitation plans for people with
      schizophrenia living in RFs should also consider mediators of change in
      subjective QOL such as satisfaction with mental health services.

PMID- 24582502
TI  - Non-homologous end joining: emerging themes and unanswered questions.
AB  - Non-homologous end joining (NHEJ) is the major pathway for the repair of ionizing
      radiation induced DNA double strand breaks in human cells. Here, we discuss
      current insights into the mechanism of NHEJ and the interplay between NHEJ and
      other pathways for repair of IR-induced DNA damage. 

PMID- 24582506
TI  - Community experience of vemurafenib for BRAF(V600) melanoma.

PMID- 24582505
TI  - Vemurafenib in patients with BRAF(V600) mutated metastatic melanoma: an open
      label, multicentre, safety study.
AB  - BACKGROUND: The orally available BRAF kinase inhibitor vemurafenib, compared with
      dacarbazine, shows improved response rates, progression-free survival (PFS), and
      overall survival in patients with metastatic melanoma that has a BRAF(V600)
      mutation. We assessed vemurafenib in patients with advanced metastatic melanoma
      with BRAF(V600) mutations who had few treatment options. METHODS: In an open
      label, multicentre study, patients with untreated or previously treated melanoma
      and a BRAF(V600) mutation received oral vemurafenib 960 mg twice a day. The
      primary endpoint was safety. All analyses were done on the safety population,
      which included all patients who received at least one dose of vemurafenib. This
      report is the third interim analysis of this study. This study is registered with
      ClinicalTrials.gov, number NCT01307397. FINDINGS: Between March 1, 2011, and Jan
      31, 2013, 3226 patients were enrolled in 44 countries. 3222 patients received at
      least one dose of vemurafenib (safety population). At data cutoff, 868 (27%)
      patients were on study treatment and 2354 (73%) had withdrawn, mainly because of
      disease progression. Common adverse events of all grades included rash (1592
      [49%]), arthralgia (1259 [39%]), fatigue (1093 [34%]), photosensitivity reaction
      (994 [31%]), alopecia (826 [26%]), and nausea (628 [19%]). 1480 (46%) patients
      reported grade 3 or 4 adverse events, including cutaneous squamous cell carcinoma
      (389 [12%]), rash (155 [5%]), liver function abnormalities (165 [5%]), arthralgia
      (106 [3%]), and fatigue (93 [3%]). Grade 3 and 4 adverse events were reported
      more frequently in patients aged 75 years and older (n=257; 152 [59%, 95% CI 53
      65] and ten [4%, 2-7], respectively) than in those younger than 75 years (n=2965;
      1286 [43%, 42-45] and 82 [3%, 2-3], respectively). INTERPRETATION: Vemurafenib
      safety in this diverse population of patients with BRAF(V600) mutated metastatic
      melanoma, who are more representative of routine clinical practice, was
      consistent with the safety profile shown in the pivotal trials of this drug.
      FUNDING: F Hoffmann-La Roche.

PMID- 24582507
TI  - Genotypic and symbiotic diversity of Rhizobium populations associated with
      cultivated lentil and pea in sub-humid and semi-arid regions of Eastern Algeria.
AB  - The genetic structure of rhizobia nodulating pea and lentil in Algeria, Northern
      Africa was determined. A total of 237 isolates were obtained from root nodules
      collected on lentil (Lens culinaris), proteaginous and forage pea (Pisum sativum)
      growing in two eco-climatic zones, sub-humid and semi-arid, in Eastern Algeria.
      They were characterised by PCR-restriction fragment length polymorphism (RFLP) of
      the 16S-23S rRNA intergenic region (IGS), and the nodD-F symbiotic region. The
      combination of these haplotypes allowed the isolates to be clustered into 26
      distinct genotypes, and all isolates were classified as Rhizobium leguminosarum.
      Symbiotic marker variation (nodD-F) was low but with the predominance of one nod
      haplotype (g), which had been recovered previously at a high frequency in Europe.
      Sequence analysis of the IGS further confirmed its high variability in the
      studied strains. An AMOVA analysis showed highly significant differentiation in
      the IGS haplotype distribution between populations from both eco-climatic zones.
      This differentiation was reflected by differences in dominant genotype
      frequencies. Conversely, no host plant effect was detected. The nodD gene
      sequence-based phylogeny suggested that symbiotic gene diversity in pea and
      lentil nodulating rhizobial populations in Algeria was low compared to that
      reported elsewhere in the world.

PMID- 24582508
TI  - Development of quantitative PCR and metagenomics-based approaches for strain
      quantification of a defined mixed-strain starter culture.
AB  - Although the strain composition of mixed cultures may hugely affect production of
      various fermented foods, such as e.g. cheese, tools for investigating it have so
      far been limited. In this study, two new approaches for quantification of seven
      Lactococcus lactis subsp. cremoris strains (S1-S7) in a defined mixed-strain
      starter culture were developed and verified. By mapping NGS reads from 47
      sequenced L. lactis strains to de novo assembly contigs of the seven strains, two
      strain-specific sequence regions (SEQ1 and SEQ2) were identified for each strain
      for qPCR primer design (A1 and A2). The qPCR assays amplified their strain
      specific sequence region target efficiently. Additionally, high reproducibility
      was obtained in a validation sample containing equal amounts of the seven
      strains, and assay-to-assay coefficients of variance (CVs) for six (i.e. S1, S2,
      S4-S7) of the seven strains correlated to the inter-plate CVs. Hence, at least
      for six strains, the qPCR assay design approach was successful. The metagenomics
      based approach quantified the seven strains based on average coverage of SEQ1 and
      SEQ2 by mapping sequencing reads from the validation sample to the strain
      specific sequence regions. Average coverages of the SEQ1 and SEQ2 in the
      metagenomics data showed CVs of <=17.3% for six strains (i.e. S1-S4, S6, S7).
      Thus, the metagenomics-based quantification approach was considered successful
      for six strains, regardless of the strain-specific sequence region used. When
      comparing qPCR- and metagenomics-based quantifications of the validation sample,
      the identified strain-specific sequence regions were considered suitable and
      applicable for quantification at a strain level of defined mixed-strain starter
      cultures. 

PMID- 24582509
TI  - Comments on "Sentinel lymph node biopsy versus elective neck dissection in
      patients with cT1-2 N0 oral tongue squamous cell carcinoma".

PMID- 24582510
TI  - Effects of man-made structures on sedimentary oxygenation: extent, seasonality
      and implications for offshore renewables.
AB  - The number of man-made structures to be placed in the marine environment is set
      to increase massively in the near future as a consequence of the wide-scale
      adoption and commercialisation of offshore electricity generation. Marine
      renewable energy devices (MREDs) interact with their receiving environment and
      are de-facto artificial reefs. The Loch Linnhe Artificial Reef (LLR) complex is a
      large-scale experimental facility, with the main matrix consisting of 30 separate
      reef modules deployed in 10-30 m depth and over a gradient of hydrographic and
      sedimentological conditions. The LLR offers potential to examine impacts that are
      analogous to those likely to occur around MREDs. The extent of the impact of the
      LLR modules on the receiving environment was assessed by determining their effect
      on sedimentary redox potential, as a function of distance from the reef-edge, and
      season, using an innovative, hand-held, underwater redox probe. The results are
      commensurate with the reef-proximal baffling of water flow resulting in the
      entrapment of drifting phytodetritus. At the least current-exposed reef-group the
      expected decrease in mean redox, at 80 mm sediment depth, was 80 mV (95% CI 40,
      120 mV) but this effect was not observed more than 1 m from the reef edge and
      only occurred during summer months (water temperature >10  degrees C). Redox at
      the reef edge, particularly during summer months, was more variable compared to
      redox taken at 1 m and 4 m reef-distance and was associated with the patchy
      distribution of phytodetrital accumulations. At all reef groups, there was no
      discernible difference in modelled mean redox between observations taken at 1 m
      and 4 m-reef distance. Artificial structures, including MREDs, may cause quite
      major sedimentary changes but this evidence suggests that these effects will be
      of limited spatial scale and, where phytodetrital accumulations occur, are only
      likely to be detrimental in oxygen-deficient sediments. Where these changes occur
      at well-flushed sites they are likely to be associated with increased infaunal
      biomass typical of moderate organic enrichment. 

PMID- 24582511
TI  - Are Apodemus spp. mice and Myodes glareolus reservoirs for Borrelia miyamotoi,
      Candidatus Neoehrlichia mikurensis, Rickettsia helvetica, R. monacensis and
      Anaplasma phagocytophilum?
AB  - In Europe, in addition to Borrelia burgdorferi sensu lato and tick-borne
      encephalitis (TBE) virus, other zoonotic pathogens, like B. miyamotoi, a species
      related to the relapsing fever spirochaetes, Candidatus Neoehrlichia mikurensis
      (N. mikurensis), Rickettsia helvetica, Rickettsia monacensis, and Anaplasma
      phagocytophilum have been reported in the ixodid tick Ixodes ricinus. No study
      was conducted to identify reservoir hosts for these pathogens. Here, we
      investigated the role played by wild rodents in the natural transmission cycle of
      B. miyamotoi, N. mikurensis, R. helvetica, R. monacensis, and A. phagocytophilum
      in Switzerland. In 2011 and 2012, small mammals were captured in an area where
      these pathogens occur in questing ticks. Ixodes ricinus ticks infesting captured
      small mammals were analysed after their moult by PCR followed by reverse line
      blot to detect the different pathogens. Xenodiagnostic larvae were used to
      evaluate the role of rodents as reservoirs and analysed after their moult. Most
      of the 108 captured rodents (95.4%) were infested by I. ricinus ticks; 4.9%,
      3.9%, 24.0%, and 0% of the rodents were infested by Borrelia, N. mikurensis,
      Rickettsia spp., and A. phagocytophilum-infected larvae, respectively. Borrelia
      afzelii, B. miyamotoi, N. mikurensis, Rickettsia spp., and A. phagocytophilum
      were detected in 2.8%, 0.17%, 2.6%, 6.8%, and 0% of the ticks attached to
      rodents, respectively. Borrelia afzelii was transmitted by 4 rodents to 41.2% of
      the xenodiagnostic ticks, B. miyamotoi by 3 rodents to 23.8%, and N. mikurensis
      was transmitted by 6 rodents to 41.0% of the xenodiagnostic ticks. None of the
      tested rodent transmitted Rickettsia spp. or A. phagocytophilum to I. ricinus
      xenodiagnostic larvae. This study showed that rodents are reservoir hosts for B.
      miyamotoi and N. mikurensis in Europe. 

PMID- 24582513
TI  - Vector biodiversity did not associate with tick-borne pathogen prevalence in
      small mammal communities in northern and central California.
AB  - Vector and host abundance affect infection transmission rates, prevalence, and
      persistence in communities. Biological diversity in hosts and vectors may provide
      "rescue" hosts which buffer against pathogen extinction and "dilution" hosts
      which reduce the force of infection in communities. Anaplasma phagocytophilum is
      a tick-transmitted zoonotic pathogen that circulates in small mammal and tick
      communities characterized by varying levels of biological diversity. We examined
      the prevalence of A. phagocytophilum in Ixodes spp. ticks in 11 communities in
      northern and central California. A total of 1020 ticks of 8 species was
      evaluated. Five percent of ticks (5 species) were PCR-positive, with the highest
      prevalence (6-7%) in I. pacificus and I. ochotonae. In most species, adults had a
      higher prevalence than nymphs or larvae. PCR prevalence varied between 0% and 40%
      across sites; the infection probability in ticks increased with infestation load
      and prevalence in small mammals, but not tick species richness, diversity,
      evenness, or small mammal species richness. No particular tick species was likely
      to "rescue" infection in the community; rather the risk of A. phagocytophilum
      infection is related to exposure to particular tick species and life stages, and
      overall tick abundance. 

PMID- 24582514
TI  - Gait kinematics of people with multiple sclerosis and the acute application of
      functional electrical stimulation.
AB  - This study aimed to (i) compare the gait characteristics of people with Multiple
      Sclerosis (pwMS) to those of healthy controls walking at the same average speed,
      and (ii) assess the effects of the acute application of Functional Electrical
      Stimulation (FES) to the dorsiflexors. Twenty-two people with pwMS (mean age 49
      years), prescribed FES, and 11 age matched healthy controls participated. Three
      dimensional gait kinematics were assessed whilst (i) pwMS and healthy controls
      walked at self-selected speeds (SSWS), (ii) healthy controls also walked at the
      average walking speed of the pwMS group, and (iii) people with MS walked using
      FES. Compared to healthy controls walking at their SSWS, pwMS walked slower and
      showed differences in nearly all gait characteristics (p<0.001). Compared to
      healthy controls walking at the same average speed, pwMS still exhibited
      significantly shorter stride length (p=0.007), reduced dorsiflexion at initial
      contact (p=0.002), reduced plantar flexion at terminal stance (p=0.008) and
      reduced knee flexion in swing (p=0.002). However, no significant differences were
      seen between groups in double support duration (p=0.617), or hip range of motion
      (p=0.291). Acute application of FES resulted in a shift towards more normal gait
      characteristics, except for plantar flexion at terminal stance which decreased.
      In conclusion, compared to healthy controls, pwMS exhibit impairment of several
      characteristics that appear to be independent of the slower walking speed of
      pwMS. The acute application of FES improved most impaired gait kinematics. A
      speed matched control group is warranted in future studies of gait kinematics of
      pwMS.

PMID- 24582512
TI  - Comparative bioinformatics, temporal and spatial expression analyses of Ixodes
      scapularis organic anion transporting polypeptides.
AB  - Organic anion-transporting polypeptides (Oatps) are an integral part of the
      detoxification mechanism in vertebrates and invertebrates. These cell surface
      proteins are involved in mediating the sodium-independent uptake and/or
      distribution of a broad array of organic amphipathic compounds and xenobiotic
      drugs. This study describes bioinformatics and biological characterization of 9
      Oatp sequences in the Ixodes scapularis genome. These sequences have been
      annotated on the basis of 12 transmembrane domains, consensus motif D-X-RW-(I,V)
      GAWW-X-G-(F,L)-L, and 11 conserved cysteine amino acid residues in the large
      extracellular loop 5 that characterize the Oatp superfamily. Ixodes scapularis
      Oatps may regulate non-redundant cross-tick species conserved functions in that
      they did not cluster as a monolithic group on the phylogeny tree and that they
      have orthologs in other ticks. Phylogeny clustering patterns also suggest that
      some tick Oatp sequences transport substrates that are similar to those of body
      louse, mosquito, eye worm, and filarial worm Oatps. Semi-quantitative RT-PCR
      analysis demonstrated that all 9 I. scapularis Oatp sequences were expressed
      during tick feeding. Ixodes scapularis Oatp genes potentially regulate functions
      during early and/or late-stage tick feeding as revealed by normalized mRNA
      profiles. Normalized transcript abundance indicates that I. scapularis Oatp genes
      are strongly expressed in unfed ticks during the first 24h of feeding and/or at
      the end of the tick feeding process. Except for 2 I. scapularis Oatps, which were
      expressed in the salivary glands and ovaries, all other genes were expressed in
      all tested organs, suggesting the significance of I. scapularis Oatps in
      maintaining tick homeostasis. Different I. scapularis Oatp mRNA expression
      patterns were detected and discussed with reference to different physiological
      states of unfed and feeding ticks. 

PMID- 24582515
TI  - Mediolateral foot placement ability during ambulation in individuals with chronic
      post-stroke hemiplegia.
AB  - Mediolateral (ML) foot placement is an effective way to redirect the lateral
      trajectory of the body center of mass (BCoM) during ambulation, but has only been
      partly characterized in the chronic post-stroke population despite their
      increased risk for falling [1]. During able-bodied gait, the locomotor system
      coordinates lower limb swing phase kinematics such that an appropriate ML foot
      placement occurs upon foot contact. Muscle weakness and abnormal motor patterns
      may impair foot placement ability post-stroke. The purpose of this study was to
      characterize ML foot placement ability during post-stroke ambulation by
      quantifying ML foot placement accuracy and precision, for the both sound and
      affected feet. Age matched able-bodied individuals were recruited for comparison.
      All participants were instructed to target step widths ranging from 0 to 45% leg
      length, as marked on the laboratory floor. Results of this study confirmed that
      ML foot placement accuracy and precision were significantly lower for the post
      stroke group as compared to the control group (p=0.0). However, ML foot placement
      accuracy and precision were not significantly different between the affected and
      sound limbs in the post-stroke group. The lowest accuracy for post-stroke
      subjects was observed at both extreme step width targets (0 and 45%). Future work
      should explore potential mechanisms underlying these findings such as abnormal
      motor coordination, lower limb muscle strength, and abnormal swing phase movement
      patterns.

PMID- 24582516
TI  - Targeted therapies in metastatic esophageal cancer: advances over the past
      decade.
AB  - Esophageal cancer is one of the most aggressive malignancies of the upper
      aerodigestive tract. Despite advances in surgical techniques and multi-modality
      therapies, the 5-year survival rate remains poor (14%). Over the past decade,
      efforts have been focused on the field of drug development with the advancement
      of novel molecularly targeted therapeutic agents. These agents target a variety
      of cancer relevant pathways such as vascular endothelial growth factor (VEGF) or
      its receptor, the cyclooxygenase-2 (COX-2), epidermal growth factor receptor
      (EGFR), and mammalian target of rapamycin (mTOR) pathways. The number of approved
      targeted agents remains few, with HER-2 inhibitors leading the list for treatment
      of HER-2 expressing metastatic adenocarcinomas. Novel agents have not yet been
      widely explored in esophageal cancer. In this review, we will provide a concise
      and systematic overview of the development of novel targeted therapies currently
      under investigation for the treatment of metastatic esophageal disease. 

PMID- 24582517
TI  - [Validation of a method for notifying and monitoring medication errors in
      pediatrics].
AB  - OBJECTIVE: To analyze the impact of a multidisciplinary and decentralized safety
      committee in the pediatric management unit, and the joint implementation of a
      computing network application for reporting medication errors, monitoring the
      follow-up of the errors, and an analysis of the improvements introduced. MATERIAL
      AND METHODS: An observational, descriptive, cross-sectional, pre-post
      intervention study was performed. An analysis was made of medication errors
      reported to the central safety committee in the twelve months prior to
      introduction, and those reported to the decentralized safety committee in the
      management unit in the nine months after implementation, using the computer
      application, and the strategies generated by the analysis of reported errors.
      MEASURED VARIABLES: Number of reported errors/10,000 days of stay, number of
      reported errors with harm per 10,000 days of stay, types of error, categories
      based on severity, stage of the process, and groups involved in the notification
      of medication errors. RESULTS: Reported medication errors increased 4.6 -fold,
      from 7.6 notifications of medication errors per 10,000 days of stay in the pre
      intervention period to 36 in the post-intervention, rate ratio 0.21 (95% CI; 0.11
      0.39) (P<.001). The medication errors with harm or requiring monitoring reported
      per 10,000 days of stay, was virtually unchanged from one period to the other
      ratio rate 0,77 (95% IC; 0,31-1,91) (P>.05). The notification of potential errors
      or errors without harm per 10,000 days of stay increased 17.4-fold (rate ratio
      0.005., 95% CI; 0.001-0.026, P<.001). CONCLUSIONS: The increase in medication
      errors notified in the post-intervention period is a reflection of an increase in
      the motivation of health professionals to report errors through this new method.

PMID- 24582518
TI  - [Partial splenectomy in sickle cell disease].
AB  - INTRODUCTION: Total splenectomy in sickle cell disease is related to a high risk
      of fulminant sepsis and increased incidence of other events, which have not been
      reported in patients with partial splenectomy. In this study we examined the
      patients with sickle cell disease and partial splenectomy and compared the
      clinical and laboratory results with non-splenectomized patients. MATERIAL AND
      METHODS: We studied 54 patients with sickle cell disease who underwent partial
      splenectomy in childhood from 1986 until 2011 at the Institute of Hematology and
      Immunology. They were compared with 54 non-splenectomized patients selected by
      random sampling with similar characteristics. RESULTS: Partial splenectomy was
      performed at a mean age of 4.1 years, with a higher frequency in homozygous
      hemoglobin S (70.4%), and the most common cause was recurrent splenic
      sequestration crisis. The most common postoperative complications were fever of
      unknown origin (14.8%) and acute chest syndrome (11.1%). After splenectomy there
      was a significant increase in leukocytes, neutrophils, and platelets, the latter
      two parameters remained significantly elevated when compared with non
      splenectomized patients. There was no difference in the incidence of clinical
      events, except hepatic sequestration, which was more common in splenectomized
      patients. CONCLUSION: Partial splenectomy was a safe procedure in patients with
      sickle cell disease. There were no differences in the clinical picture in
      children splenectomized and non-splenectomized except the greater frequency of
      hepatic sequestration crisis in the first group.

PMID- 24582519
TI  - [Association between nutritional status and physical abilities in children aged 6
      to 18 years in Medellin (Colombia)].
AB  - INTRODUCTION: Nutritional disorders in childhood may cause a decline in motor
      abilities and increased morbidity and mortality in adulthood. OBJECTIVE: To
      assess the association between nutritional status and motor abilities. MATERIALS
      AND METHODS: A cross-sectional study was performed that included 12,872 children
      aged between 6 and 18 years who underwent a clinical evaluation and various
      physical tests. RESULTS: Among the children, 66% had a Tanner maturation stage 1
      and 2, 6% were under-nourished, and 12.2% were at risk of overweight and obesity.
      The obese children had a decrease in aerobic power (in 2.72 mL O2 kg(-1).min(-1);
      95%CI: 1.89 to 3.56; P<.001), speed (0.14m.sec; 95%CI: 0.06 to 0.22; P<.001),
      explosive strength (0.10 m; 95%CI: 0.06 to 0.13; P<.001), agility, strength
      endurance and balance. Under-nourished children showed a decrease in speed (0.13
      m.sec; 95%CI: 0.06 to 0.20; P<.001), explosive strength (0.04 m; 95%CI: 0.01 to 0
      07; P<.004), and strength endurance. CONCLUSIONS: There was an association
      between nutritional status and motor abilities in the children included in this
      study. Obese children showed the worst results in physical tests, and the under
      nourished ones showed a decrease in speed, explosive strength and strength
      endurance.

PMID- 24582520
TI  - [Influence of in-home nursing care on the weight of the early discharged preterm
      newborn].
AB  - INTRODUCTION: In-Home nursing care of the preterm newborn helps to bring the
      family situation to normal, promotes breastfeeding and development of the
      newborn, and enables the reorganization of health care resources. The purpose of
      this paper is to demonstrate that in-home nursing care of the preterm newborn
      leads to an increase in weight and a similar morbidity. PATIENTS AND METHODOLOGY:
      A total of 65 cases and 65 controls (matched by weight, age and sex) were
      studied, all of them preterm newborns born in hospital and weighing less than
      2100 g at discharge. In-home nursing care was carried out by a pediatrician
      neonatologist, as well as two nurses specialized in neonatology who made several
      visits to the home. Weight gain was calculated as g/day and g/Kg/day, comparing
      the first week of the study with the week prior to the beginning of the study.
      RESULTS: The groups were comparable. Weight gain in the group with home nursing
      care was 38 g per day, significantly higher than the weight gain in the control
      group (31 g/day). The independent predictive variables of the increase in
      g/Kg/day during the study were in-home nursing care, male gender, breastfeeding
      less, and not having suffered from a peri-intraventricular hemorrhage. Neonatal
      morbidity was similar in both groups. CONCLUSIONS: In-home care was associated
      with a greater weight gain of the newborn at home than during their stay in the
      hospital, and can be considered safe because neonatal morbidity was not
      increased.

PMID- 24582521
TI  - Single-embryo transfer of vitrified-warmed blastocysts yields equivalent live
      birth rates and improved neonatal outcomes compared with fresh transfers.
AB  - OBJECTIVE: To compare pregnancy and neonatal outcomes after fresh and vitrified
      warmed single-blastocyst transfers. DESIGN: Retrospective study. SETTING: Private
      in vitro fertilization (IVF) clinic. PATIENT(S): 1,209 infertile patients who
      underwent a total of 1,157 fresh and 645 vitrified-warmed embryo transfers.
      INTERVENTION(S): Day-5 single-blastocyst transfers using fresh or vitrified
      warmed (Cryotop method) grade I and grade II embryos. MAIN OUTCOME MEASURE(S):
      Fetal heart pregnancy rate, live-birth rate, gestational age, and live-birth
      weight. RESULT(S): The overall blastocyst thaw survival rate was 94.4% and was
      not significantly different between blastocyst grades or developmental stages.
      Similar clinical outcomes were achieved for fresh and vitrified-warmed blastocyst
      transfers; for example, grade I blastocysts had a live-birth rate of 52.8% versus
      55.3%, respectively, and grade II blastocysts had a rate of 34.9% versus 30.4%,
      respectively. Significantly improved neonatal outcomes were evident for vitrified
      warmed blastocyst transfers for gestational age, being on average 0.3 weeks
      longer, and for live-birth weight with babies born on average 145 g heavier
      (3,296 g versus 3,441 g for fresh and vitrified-warmed groups, respectively), as
      compared with fresh transfers. CONCLUSION(S): Embryo transfer of vitrified-warmed
      blastocysts yields equivalent live-birth rates and improved neonatal outcomes
      compared with fresh transfers.

PMID- 24582523
TI  - Discrimination and simultaneous detection of two myxozoan parasites belonging to
      genus Thelohanellus by multiplex polymerase chain reaction.
AB  - Thelohanellus kitauei and Thelohanellus hovorkai are myxozoan parasites
      pathogenic in cyprinid fish especially adult Israel carp and common carp. In the
      present study, the complete 18S rRNA-ITS1-5.8S rRNA-ITS2 sequences of these two
      Thelohanellus species were cloned with primers designed from information from
      Genbank and previous studies. The results revealed that ITS1 and ITS2 sequences
      of T. kitauei and T. hovorkai were clearly distinguished although the 18S rRNA
      regions of the two parasites were highly conserved. Based on these sequences, new
      primer sets were designed for specific identification of these two parasites by
      multiplex PCR. Both single and multiplex PCR methods using these primers could
      identify these two myxozoan parasites from mixed DNA samples successfully. Our
      findings provide a powerful tool for the differentiation of the highly similar
      pathogenic Thelohanellus species for specific detection for the early diagnosis
      of diseases. 

PMID- 24582522
TI  - First clinical uterus transplantation trial: a six-month report.
AB  - OBJECTIVE: To report the 6-month results of the first clinical uterus
      transplantation (UTx) trial. This type of transplantation may become a treatment
      of absolute uterine-factor infertility (AUFI). DESIGN: Prospective observational
      study. SETTING: University hospital. PATIENT(S): Nine AUFI women and their live
      uterine donors, the majority being mothers. INTERVENTION(S): Live-donor UTx and
      low-dose induction immunosuppression. MAIN OUTCOME MEASURE(S): Data from
      preoperative investigations, surgery and follow-up for 6 months. RESULT(S):
      Durations of donor and recipient surgery ranged from 10 to 13 hours and from 4 to
      6 hours, respectively. No immediate perioperative complications occurred in any
      of the recipients. After 6 months, seven uteri remained viable with regular
      menses. Mild rejection episodes occurred in four of these patients. These
      rejection episodes were effectively reversed by corticosteroid boluses. The two
      graft losses were because of acute bilateral thrombotic uterine artery occlusions
      and persistent intrauterine infection. CONCLUSION(S): The results demonstrate the
      feasibility of live-donor UTx with a low-dose immunosuppressive protocol.
      CLINICAL TRIAL REGISTRATION NUMBER: NCT01844362.

PMID- 24582524
TI  - Seroprevalence of Babesia caballi and Theileria equi in five draught equine
      populated metropolises of Punjab, Pakistan.
AB  - Equine piroplasmosis (EP) caused by intraerythrocytic parasites (Theileria equi
      and Babesia caballi) is an emerging equine disease of world-wide distribution. In
      Pakistan, the prevalence and incidence of EP are unknown. In order to obtain the
      first insights into the prevalence of the disease, a total of 430 equids,
      including 33 mules, 65 horses and 332 donkeys, aging from <= 5 to >= 10 years of
      either sex, from five metropolises of Punjab, Pakistan, were serologically tested
      for the presence of antibodies directed against B. caballi and T. equi, using a
      competitive enzyme-linked immunosorbent assay (cELISA). Out of 430 equid serum
      samples tested, 226 (52.6%, 95% CI 47.7-57.4) were found cELISA positive for EP
      (T. equi and/or B. caballi infections). The overall seroprevalence of EP was
      41.2% (95% CI 36.5-46.0) for T. equi and 21.6% (95% CI 17.8-25.8) for B. caballi.
      A small proportion of equids (10.2%, 95% CI 7.5-13.5) was seropositive for both
      T. equi and B. caballi. Seroprevalence of T. equi was significantly higher
      (P<0.01) in equines from the metropolis of Lahore (66.7%, 95% CI 54.3-77.6) and
      in horses (56.9%, 95% CI 44.0-69.2). Multivariable logistic regression model
      analysis indicated that factors associated with prevalence of EP were being an
      equine species kept in metropolis Lahore (OR=4.24, 95% CI 2.28-7.90), horse
      (OR=2.82, 95% CI 1.53-5.20) and male equids (OR=1.81, 95% CI 1.15-2.86).

PMID- 24582525
TI  - Observations on the phenotypic relationships between anti-CarLA salivary IgA
      antibody response, nematode infection levels and growth rates in farmed red
      (Cervus elaphus) and wapiti hybrid deer (Cervus elaphus canadensis).
AB  - Nematode parasites are one of the most significant production limiting factors in
      farmed deer in New Zealand. One long term strategy to reduce reliance on
      anthelmintics is to select deer that develop resistance to parasites. It has been
      shown in sheep that secretory antibody (IgA) in the saliva against a Carbohydrate
      Larval Antigen (CarLA) on infective larvae (L3) of a wide range of gastro
      intestinal nematodes protects against reinfection. This paper describes a
      longitudinal slaughter study undertaken to measure anti-CarLA IgA antibody (CarLA
      IgA) levels in the saliva of 5-12 month old farmed red and wapiti-cross-red deer
      (wapx) grazed together and to attempt to relate these levels to parasite burdens
      and productivity. The study showed that salivary CarLA-IgA levels peaked in June
      (late autumn) and October (mid spring), but the levels in wapx deer were
      significantly lower than in red deer. Over the May-December period 55% of red
      deer had CarLA-IgA values >=2 units compared with 26% of wapx deer and over this
      period red deer had consistently lower adult abomasal parasite burdens than wapx
      deer. The average number of adult abomasal nematodes was significantly lower at
      each slaughter from May to December for all deer with CarLA-IgA >=2 units vs <2
      units. There were no demonstrable correlations with liveweight gain in these
      small groups of deer. 

PMID- 24582526
TI  - Cross-sectional analysis of the seropositivity and risk factors of Toxoplasma
      gondii infection among veterinarians, in relation to their public professional
      activities.
AB  - Toxoplasma gondii is a zoonotic pathogen that can infect most warm-blooded
      animals and humans. Although numerous epidemiological studies of T. gondii have
      been published, very limited data exist on the prevalence of T. gondii infection
      among veterinarians. In this study, a survey was used to analyze the
      seropositivity of and risk factors for T. gondii infection among public
      veterinarians (PV) and veterinarians in veterinary service laboratories (VVSL).
      Blood samples were collected from individuals in both groups and examined by
      enzyme immunoassay (EIA). A questionnaire survey on work activities and personal
      dietary habits was also conducted. The positive rate for specific anti-T. gondii
      IgG antibody was 8% overall, comprising 13.4% in the PV group and 5.5% in the
      VVSL group. The seropositivity of T. gondii infection in the PV group was
      significantly related to involvement with the enforced destruction and contact
      with animals that were infected with zoonotic pathogens. Consumption of raw pork
      and drinking unboiled groundwater were also critical dietary risk factors for
      seropositivity for T. gondii infection. This is the first study of the factors
      that contribute to T. gondii infection among veterinarians with public
      professional activities in Korea. Further preventive educational programs for
      veterinarians with public professional activities are necessary to prevent
      exposure to T. gondii infection in this population. 

PMID- 24582527
TI  - Altered neuronal activity and differential sensitivity to acute antidepressants
      of locus coeruleus and dorsal raphe nucleus in Wistar Kyoto rats: a comparative
      study with Sprague Dawley and Wistar rats.
AB  - The Wistar Kyoto rat (WKY) has been proposed as an animal model of depression.
      The noradrenergic nucleus, locus coeruleus (LC) and the serotonergic nucleus,
      dorsal raphe (DRN) have been widely implicated in the ethiopathology of this
      disease. Thus, the goal of the present study was to investigate in vivo the
      electrophysiological properties of LC and DRN neurons from WKY rats, using single
      unit extracellular techniques. Wistar (Wis) and Sprague Dawley (SD) rats were
      used as control strains. In the LC from WKY rats the basal firing rate was higher
      than that obtained in the Wis and SD strain, and burst firing activity also was
      greater compared to that in Wis strain but not in SD. The sensitivity of LC
      neurons to the inhibitory effect of the alpha2-adrenoceptor agonist, clonidine
      and the antidepressant reboxetine was lower in WKY rats compared to Wis, but not
      SD. Regarding DRN neurons, in WKY rats burst activity was lower than that
      obtained in Wis and SD rats, although no differences were observed in other
      firing parameters. Interestingly, while the sensitivity of DRN neurons to the
      inhibitory effect of the 5-HT1A receptor agonist, 8-OH-DPAT was lower in the WKY
      strain, the antidepressant fluoxetine had a greater inhibitory potency in this
      rat strain compared to that recorded in the Wis group. Overall, these results
      point out important electrophysiological differences regarding noradrenergic and
      serotonergic systems between Wis and WKY rats, supporting the utility of the WKY
      rat as an important tool in the research of cellular basis of depression. 

PMID- 24582528
TI  - Bat-derived influenza-like viruses H17N10 and H18N11.
AB  - Shorebirds and waterfowls are believed to be the reservoir hosts for influenza
      viruses, whereas swine putatively act as mixing vessels. The recent
      identification of two influenza-like virus genomes (designated H17N10 and H18N11)
      from bats has challenged this notion. A crucial question concerns the role bats
      might play in influenza virus ecology. Structural and functional studies of the
      two major surface envelope proteins, hemagglutinin (HA) and neuraminidase (NA),
      demonstrate that neither has canonical HA or NA functions found in influenza
      viruses. However, putative functional modules and domains in other encoded
      proteins are conserved, and the N-terminal domain of the H17N10 polymerase
      subunit PA has a classical structure and function. Therefore, potential genomic
      reassortments of such influenza-like viruses with canonical influenza viruses
      cannot be excluded at this point and should be assessed. 

PMID- 24582529
TI  - To acquire or resist: the complex biological effects of CRISPR-Cas systems.
AB  - Prokaryotic CRISPR-Cas (clustered regularly interspaced short palindromic repeat
      CRISPR associated) systems provide a sophisticated adaptive immune system that
      offers protection against foreign DNA. These systems are widely distributed in
      prokaryotes and exert an important influence on bacterial behavior and evolution.
      However, interpreting the biological effects of a CRISPR-Cas system within a
      given species can be complicated because the outcome of rejecting foreign DNA
      does not always provide a fitness advantage, as foreign DNA uptake is sometimes
      beneficial. To address these issues, here we review data pertaining to the
      potential in vivo costs and benefits of CRISPR-Cas systems, novel functions for
      these systems, and how they may be inactivated. 

PMID- 24582531
TI  - Blood pressure in acute stroke.

PMID- 24582530
TI  - Acute post-stroke blood pressure relative to premorbid levels in intracerebral
      haemorrhage versus major ischaemic stroke: a population-based study.
AB  - BACKGROUND: It is often assumed that blood pressure increases acutely after major
      stroke, resulting in so-called post-stroke hypertension. In view of evidence that
      the risks and benefits of blood pressure-lowering treatment in acute stroke might
      differ between patients with major ischaemic stroke and those with primary
      intracerebral haemorrhage, we compared acute-phase and premorbid blood pressure
      levels in these two disorders. METHODS: In a population-based study in
      Oxfordshire, UK, we recruited all patients presenting with stroke between April
      1, 2002, and March 31, 2012. We compared all acute-phase post-event blood
      pressure readings with premorbid readings from 10-year primary care records in
      all patients with acute major ischaemic stroke (National Institutes of Health
      Stroke Scale >3) versus those with acute intracerebral haemorrhage. FINDINGS: Of
      653 consecutive eligible patients, premorbid and acute-phase blood pressure
      readings were available for 636 (97%) individuals. Premorbid blood pressure
      (total readings 13,244) had been measured on a median of 17 separate occasions
      per patient (IQR 8-31). In patients with ischaemic stroke, the first acute-phase
      systolic blood pressure was much lower than after intracerebral haemorrhage
      (158.5 mm Hg [SD 30.1] vs 189.8 mm Hg [38.5], p<0.0001; for patients not on
      antihypertensive treatment 159.2 mm Hg [27.8] vs 193.4 mm Hg [37.4], p<0.0001),
      was little higher than premorbid levels (increase of 10.6 mm Hg vs 10-year mean
      premorbid level), and decreased only slightly during the first 24 h (mean
      decrease from <90 min to 24 h 13.6 mm Hg). By contrast with findings in ischaemic
      stroke, the mean first systolic blood pressure after intracerebral haemorrhage
      was substantially higher than premorbid levels (mean increase of 40.7 mm Hg,
      p<0.0001) and fell substantially in the first 24 h (mean decrease of 41.1 mm Hg;
      p=0.0007 for difference from decrease in ischaemic stroke). Mean systolic blood
      pressure also increased steeply in the days and weeks before intracerebral
      haemorrhage (regression p<0.0001) but not before ischaemic stroke. Consequently,
      the first acute-phase blood pressure reading after primary intracerebral
      haemorrhage was more likely than after ischaemic stroke to be the highest ever
      recorded (OR 3.4, 95% CI 2.3-5.2, p<0.0001). In patients with intracerebral
      haemorrhage seen within 90 min, the highest systolic blood pressure within 3 h of
      onset was 50 mm Hg higher, on average, than the maximum premorbid level whereas
      that after ischaemic stroke was 5.2 mm Hg lower (p<0.0001). INTERPRETATION: Our
      findings suggest that systolic blood pressure is substantially raised compared
      with usual premorbid levels after intracerebral haemorrhage, whereas acute-phase
      systolic blood pressure after major ischaemic stroke is much closer to the
      accustomed long-term premorbid level, providing a potential explanation for why
      the risks and benefits of lowering blood pressure acutely after stroke might be
      expected to differ. FUNDING: Wellcome Trust, Wolfson Foundation, UK Medical
      Research Council, Stroke Association, British Heart Foundation, National
      Institute for Health Research.

PMID- 24582533
TI  - [The other inequities in health care: A challenge for bioethics].
AB  - Contrary to what one may think health and equity are not issues that have always
      gone hand in hand following the formal recognition of the former by the Universal
      Declaration of Human Rights (1948). It was not until the Alma Ata Declaration in
      1978 when the close ties between both began to be seriously considered, and in
      2000 this led to several international organizations formalizing their concern
      for the factors that determine whether a health system is fair or not. Since
      then, the term "equity in health" has taken on a special meaning when weighing up
      the strength or weaknesses of certain health systems. However, over the years,
      equity in health has gradually been identified almost exclusively with a
      financial issue that focuses on distributing health resources. As a result, one
      often forgets to provide the necessary care for those in other unfair situations,
      which, as regards access to and providing health care, leads to unfair situations
      that are not directly related to financial reasons and do not require
      investments, but consensus and the honest determination to make changes. This
      leads the Bioethics of the 21st century to face two challenges: to warn of these
      inequities and to promote initiatives that are able to make effective changes.

PMID- 24582534
TI  - [Patient handoffs: Problems and solutions].

PMID- 24582532
TI  - Impact of high-dose atorvastatin therapy and clinical risk factors on incident
      aortic valve stenosis in patients with cardiovascular disease (from TNT, IDEAL,
      and SPARCL).
AB  - Clinical trials have not provided evidence for a role of statin therapy in
      reducing aortic valve stenosis (AVS) severity in patients with documented AVS.
      However, whether statin therapy could prevent the onset of AVS is unknown. Our
      objectives were (1) to compare the incidence rates of AVS among patients treated
      with high-dose versus usual-dose statin or placebo and (2) to identify clinical
      risk factors associated with the development of AVS. We conducted post hoc
      analyses in 23,508 participants from 3 large-scale multicenter atorvastatin
      randomized blinded clinical trials: Treating to New Targets, the Incremental
      Decrease in End Points Through Aggressive Lipid Lowering, and the Stroke
      Prevention by Aggressive Reduction in Cholesterol Levels. The main outcome
      measure was the incidence of clinical AVS over a median follow-up of 4.9 years
      (82 cases). Among patients who developed AVS, 39 (47.6%) were treated with
      atorvastatin 80 mg and 43 (52.4%) were treated with lower dose statin
      (atorvastatin 10 mg in Treating to New Targets, simvastatin 20 to 40 mg in
      Incremental Decrease in End Points Through Aggressive Lipid Lowering, or placebo
      in Stroke Prevention by Aggressive Reduction in Cholesterol Levels; hazard ratio
      [HR] 0.91, 95% confidence interval [CI] 0.59 to 1.41, p=0.67). In multivariate
      analyses forcing treatment, sex, and race into the model, factors that were
      significantly associated with AVS included age (HR 2.17, 95% CI 1.61 to 2.93,
      p<0.0001 per 1-SD increment), diabetes (HR 1.67, 95% CI 1.00 to 2.80, p=0.05),
      vitamin K antagonist use (HR 3.25, 95% CI 2.06 to 5.16, p<0.0001), and previous
      statin use (HR 2.65, 95% CI 1.54 to 4.60, p=0.0008). In conclusion, random
      allocation to high-dose versus usual-dose statin therapy or placebo did not
      impact the incidence of AVS among patients without known AVS. Age, diabetes,
      vitamin K antagonists, and previous statin use were significant predictors of
      incident AVS in these high-risk patients.

PMID- 24582535
TI  - Sperm protamine mRNA ratio and DNA fragmentation index represent reliable
      clinical biomarkers for men with varicocele after microsurgical varicocele
      ligation.
AB  - PURPOSE: We investigated whether the sperm protamine-1/2 mRNA ratio and DNA
      fragmentation index are reliable biomarkers in patients with clinical varicocele.
      MATERIALS AND METHODS: We performed a prospective study in 42 subfertile patients
      with left clinical varicocele and 10 normozoospermic healthy donors with proven
      fertility. All patients and female partners were seen 3 and 6 months after
      varicocelectomy for fertility examination. Real-time quantitative reverse
      transcriptase-polymerase chain reaction and SCSA(r) were performed to analyze the
      sperm protamine-1/2 mRNA ratio and DNA fragmentation index. RESULTS: The
      protamine-1/2 mRNA ratio and DNA fragmentation index were significantly higher in
      the preoperative group than in the control group (p <0.01). After varicocelectomy
      in the pregnant group the protamine-1/2 mRNA ratio recovered to the normal value
      and the DNA fragmentation index was significantly lower than in the preoperative
      group (p <0.01). In the nonpregnant group the protamine-1/2 mRNA ratio and DNA
      fragmentation index did not differ (p >0.05). However, significant differences
      were present preoperatively according to varicocele severity in the protamine-1/2
      mRNA ratio and DNA fragmentation index (p <0.05 and <0.01, respectively) with the
      highest values in the grade 3 group. Nevertheless, postoperatively no difference
      in varicocele severity was noted (p >0.05). The protamine-1/2 mRNA ratio was
      strongly related to preoperative and postoperative sperm concentration (Rs 
      0.238, p <0.01), progressive motility (Rs -0.327, p <0.01), total motility (Rs 
      0.206, p <0.05) and DNA fragmentation index (Rs 0.293, p <0.01) except for normal
      morphology (Rs -0.064, p >0.05). CONCLUSIONS: The sperm protamine-1/2 mRNA ratio
      and DNA fragmentation index can effectively be used to evaluate male fertility.
      Male infertility due to varicocele may be associated with protamine deficiency
      and sperm DNA damage. The post-varicocelectomy protamine-1/2 mRNA ratio and DNA
      fragmentation index are associated with the post-varicocelectomy pregnancy rate.

PMID- 24582536
TI  - Detection of prostate cancer by an electronic nose: a proof of principle study.
AB  - PURPOSE: We evaluate the ability of an electronic nose to discriminate prostate
      cancer from benign prostatic hyperplasia using urine headspace, potentially
      offering a clinically applicable noninvasive and rapid diagnostic method.
      MATERIALS AND METHODS: The ChemPro(r) 100-eNose was used to discriminate prostate
      cancer from benign prostatic hyperplasia using urine sample headspace. Its
      performance was tested with 50 patients with confirmed prostate cancer and 24
      samples from 15 patients with benign prostatic hyperplasia (15 patients provided
      urine preoperatively and 9 patients provided samples 3 months postoperatively)
      scheduled to undergo robotic assisted laparoscopic radical prostatectomy or
      transurethral resection of prostate, respectively. The patients provided urine
      sample preoperatively and those with benign prostatic hyperplasia also provided
      samples 3 months postoperatively to be used as a pooled control sample
      population. A discrimination classifier was identified for eNose and
      subsequently, sensitivity and specificity values were determined. Leave-one-out
      cross-validation was performed. RESULTS: Using leave-one-out cross-validation the
      eNose reached a sensitivity of 78%, a specificity of 67% and AUC 0.77.
      CONCLUSIONS: The electronic nose is capable of rapidly and noninvasively
      discriminating prostate cancer and benign prostatic hyperplasia using urine
      headspace in patients undergoing surgery.

PMID- 24582537
TI  - Autologous muscle derived cells for treatment of stress urinary incontinence in
      women.
AB  - PURPOSE: We assess the 12-month safety and potential efficacy of autologous
      muscle derived cells for urinary sphincter repair (Cook MyoSite Incorporated,
      Pittsburgh, Pennsylvania) in women with stress urinary incontinence. MATERIALS
      AND METHODS: Pooled data from 2 phase I/II studies with identical patient
      selection criteria and outcome measures were analyzed. Enrolled patients had
      stress urinary incontinence refractory to prior treatment and no symptom
      improvement during the last 6 months. Patients received intrasphincter injection
      of 10 (16), 50 (16), 100 (24) or 200*10(6) (24) autologous muscle derived cells
      for urinary sphincter repair, derived from biopsies of each patient's quadriceps
      femoris. The primary outcome measure was safety, determined by incidence and
      severity of adverse events. Potential efficacy was measured by changes in 3-day
      voiding diaries, 24-hour pad tests, and UDI-6 and IIQ-7 scores. RESULTS: A total
      of 80 patients underwent injection of autologous muscle derived cells for urinary
      sphincter repair, and 72 completed diaries and pad tests at 12-month followup. No
      adverse events attributed to autologous muscle derived cells for urinary
      sphincter repair were reported. Higher dose groups tended to have greater
      percentages of patients with at least a 50% reduction in stress leaks and pad
      weight at 12-month followup. All dose groups had statistically significant
      improvement in UDI-6 and IIQ-7 scores at 12-month followup compared to baseline.
      CONCLUSIONS: Autologous muscle derived cells for urinary sphincter repair at
      doses of 10, 50, 100 and 200*10(6) cells appears safe. Efficacy data suggest a
      potential dose response with a greater percentage of patients responsive to
      higher doses.

PMID- 24582538
TI  - Variation in prostate cancer detection rates in a statewide quality improvement
      collaborative.
AB  - PURPOSE: There remains significant controversy surrounding the optimal criteria
      for recommending prostate biopsy. To examine this issue further urologists in
      MUSIC assessed statewide prostate biopsy practice patterns and variation in
      prostate cancer detection. MATERIALS AND METHODS: MUSIC is a statewide, physician
      led collaborative designed to improve prostate cancer care. From March 2012
      through June 2013 at 17 MUSIC practices standardized clinical and pathological
      data were collected on a total of 3,015 men undergoing first-time prostate
      biopsy. We examined pathological biopsy outcomes according to patient
      characteristics and across MUSIC practices. RESULTS: The average cancer detection
      rate was 52% with significant variability across MUSIC practices (range 43% to
      70%, p<0.0001). Of all patients biopsied 27% were older than 69 years, ranging
      from 19% to 36% at individual practices. Men with prostate specific antigen less
      than 4 ng/ml comprised an average of 26% of the study population (range 10% to
      37%). The detection rate in patients older than 69 years ranged from 42% to 86%
      at individual practices (p=0.0008). In the 793 patients with prostate specific
      antigen less than 4 ng/ml the cancer detection rate ranged from 22% to 58% across
      individual practices (p=0.0065). The predicted probability of cancer detection
      varied significantly across MUSIC practices even after adjusting for patient age,
      prostate specific antigen, prostate size, family history and digital rectal
      examination findings (p<0.0001). CONCLUSIONS: While overall detection rates are
      higher than previously reported, the cancer yield of prostate biopsy varies
      widely across urology practices in Michigan. These data serve as a foundation for
      our efforts to understand and improve patient selection for prostate biopsy.

PMID- 24582539
TI  - Age and baseline quality of life at radical prostatectomy--who has the most to
      lose?
AB  - PURPOSE: Although younger men have better health related quality of life scores
      after radical prostatectomy, many have higher baseline function with more to lose
      than older men. We examined the impact of age on sexual and urinary function and
      bother during the first 2 years after radical prostatectomy. MATERIALS AND
      METHODS: Participants enrolled in CaPSURETM reported sexual and urinary scores
      before and after radical prostatectomy using UCLA-PCI. Repeated measures mixed
      models were used to compare the change in health related quality of life with
      time between men who were younger (age 60 years or less) and older (age greater
      than 60 years). Logistic regression models were used to assess associations
      between age and clinically meaningful health related quality of life decreases
      (worsening). Models were adjusted for clinical characteristics. RESULTS: Of 1,806
      patients younger men reported higher sexual and urinary function scores at each
      time point and higher sexual function decrease rates at 1 year than older men
      (81% vs 75%, p<0.01). Younger men also had higher sexual bother decrease rates 1
      year (74% vs 61%, p<0.01) and 2 years (62% vs 56%, p=0.02) after radical
      prostatectomy. On multivariate analysis age was associated with changes in sexual
      function and bother from baseline through 2 years (each p<0.01). Younger men had
      higher adjusted odds of sexual function decreases at 1 year (OR 1.15/5 years, 95%
      CI 1.01-1.30, p=0.03) but not at 2 years. Younger age was associated with lower
      odds of worsening sexual bother at 2 years (OR 0.79/5 years, 95% CI 0.67-0.94,
      p<0.01). Urinary function and bother decrease rates were similar by age.
      Secondary analyses of the age/health related quality of life interaction showed
      that men were at greater risk for health related quality of life decreases if
      baseline scores were above average regardless of age. CONCLUSIONS: Younger men
      reported higher sexual and urinary function overall, and experienced greater
      decreases in sexual function immediately after radical prostatectomy than older
      men. While the 2 groups experienced similar relative sexual function decreases at
      2 years, younger men had worse interim decreases at 1 year. Providers should
      consider these findings when discussing treatment timing, particularly with
      younger men diagnosed with early stage, low grade disease.

PMID- 24582541
TI  - Functional multiparametric magnetic resonance imaging of the kidneys using blood
      oxygen level dependent and diffusion-weighted sequences.
AB  - PURPOSE: Little data are available on noninvasive magnetic resonance imaging
      based assessment of renal function during upper urinary tract obstruction. We
      determined whether functional multiparametric kidney magnetic resonance imaging
      could monitor the treatment response in cases of acute unilateral upper urinary
      tract obstruction. MATERIAL AND METHODS: Between January 2008 and January 2010,
      18 patients with acute unilateral upper urinary tract obstruction due to calculi
      were prospectively enrolled to undergo kidney magnetic resonance imaging with
      conventional, blood oxygen level dependent and diffusion-weighted sequences upon
      emergency hospital admission and after release of obstruction. We assessed
      functional imaging parameters of obstructed and contralateral unobstructed
      kidneys derived from blood oxygen level dependent (apparent spin relaxation rate)
      and diffusion-weighted (total apparent diffusion coefficient, pure diffusion
      coefficient and perfusion fraction) sequences during acute upper urinary tract
      obstruction and after its release. RESULTS: During acute obstruction the apparent
      spin relaxation rate and perfusion fraction were lower in the cortex (p=0.020 and
      0.031) and medulla (p=0.012 and 0.190, respectively) of obstructed kidneys
      compared to contralateral unobstructed kidneys. After obstruction release the
      apparent spin relaxation rate and perfusion fraction increased in the cortex
      (p=0.016 and 0.004) and medulla (p=0.071 and 0.044, respectively) of formerly
      obstructed kidneys to values similar to those in contralateral kidneys. Total
      apparent diffusion coefficient and pure diffusion coefficient values did not
      significantly differ between obstructed and contralateral unobstructed kidneys
      during or after obstruction. CONCLUSIONS: In our patients with acute unilateral
      upper urinary tract obstruction due to calculi functional kidney magnetic
      resonance imaging using blood oxygen level dependent and diffusion-weighted
      sequences enabled us to monitor pathophysiological changes in obstructed kidneys
      during obstruction and after its release.

PMID- 24582540
TI  - Personalized medicine for the management of benign prostatic hyperplasia.
AB  - PURPOSE: Benign prostatic hyperplasia affects more than 50% of men by age 60
      years, and is the cause of millions of dollars in health care expenditure for the
      treatment of lower urinary tract symptoms and urinary obstruction. Despite the
      widespread use of medical therapy, there is no universal therapy that treats all
      men with symptomatic benign prostatic hyperplasia. At least 30% of patients do
      not respond to medical management and a subset require surgery. Significant
      advances have been made in understanding the natural history and development of
      the prostate, such as elucidating the role of the enzyme 5alpha-reductase type 2,
      and advances in genomics and biomarker discovery offer the potential for a more
      targeted approach to therapy. We review the current understanding of benign
      prostatic hyperplasia progression as well as the key genes and signaling pathways
      implicated in the process such as 5alpha-reductase. We also explore the potential
      of biomarker screening and gene specific therapies as tools to risk stratify
      patients with benign prostatic hyperplasia and identify those with symptomatic or
      medically resistant forms. MATERIALS AND METHODS: A PubMed(r) literature search
      of current and past peer reviewed literature on prostate development, lower
      urinary tract symptoms, benign prostatic hyperplasia pathogenesis, targeted
      therapy, biomarkers, epigenetics, 5alpha-reductase type 2 and personalized
      medicine was performed. An additional Google ScholarTM search was conducted to
      broaden the scope of the review. Relevant reviews and original research articles
      were examined, as were their cited references, and a synopsis of original data
      was generated with the goal of informing the practicing urologist of these
      advances and their implications. RESULTS: Benign prostatic hyperplasia is
      associated with a state of hyperplasia of the stromal and epithelial
      compartments, with 5alpha-reductase type 2 and androgen signaling having key
      roles in the development and maintenance of the prostate. Chronic inflammation,
      multiple growth factor and hormonal signaling pathways, and medical comorbidities
      have complex roles in prostate tissue homeostasis as well as its evolution into
      the clinical state of benign prostatic hyperplasia. Resistance to medical therapy
      with finasteride may occur through silencing of the 5alpha-reductase type 2 gene
      by DNA methylation, leading to a state in which 30% of adult prostates do not
      express 5alpha-reductase type 2. Novel biomarkers such as single nucleotide
      polymorphisms may be used to risk stratify patients with symptomatic benign
      prostatic hyperplasia and identify those at risk for progression or failure of
      medical therapy. Several inhibitors of the androgen receptor and other signaling
      pathways have recently been identified which appear to attenuate benign prostatic
      hyperplasia progression and may offer alternative targets for medical therapy.
      CONCLUSIONS: Progressive worsening of lower urinary tract symptoms and bladder
      outlet obstruction secondary to benign prostatic hyperplasia is the result of
      multiple pathways including androgen receptor signaling, proinflammatory
      cytokines and growth factor signals. New techniques in genomics, proteomics and
      epigenetics have led to the discovery of aberrant signaling pathways, novel
      biomarkers, DNA methylation signatures and potential gene specific targets. As
      personalized medicine continues to develop, the ability to risk stratify patients
      with symptomatic benign prostatic hyperplasia, identify those at higher risk for
      progression, and seek alternative therapies for those in whom conventional
      options are likely to fail will become the standard of targeted therapy.

PMID- 24582542
TI  - Retinal proteins - you can teach an old dog new tricks.

PMID- 24582544
TI  - Surgical or percutaneous hepatic artery cannulation for chemotherapy.
AB  - The principle underlying administration of hepatic arterial chemotherapy (HACT)
      is to increase the local concentration of cytotoxic chemotherapy while limiting
      systemic toxicity. The chemotherapy agent is infused into the hepatic artery
      distal to branches that serve the stomach, duodenum, and pancreas. The intra
      arterial catheter is connected to a subcutaneously implanted reservoir to allow
      repeated sessions of chemotherapy. Percutaneous placement is now a reliable and
      reproducible technique in the hands of well-trained interventional radiologists.
      Hepatic arterial cannulation by an open surgical approach is currently reserved
      for cases where the decision for HACT is made in the course of an hepatic
      surgical procedure. 

PMID- 24582543
TI  - Molecular deconstruction, detection, and computational prediction of
      microenvironment-modulated cellular responses to cancer therapeutics.
AB  - The field of bioengineering has pioneered the application of new precision
      fabrication technologies to model the different geometric, physical or molecular
      components of tissue microenvironments on solid-state substrata. Tissue
      engineering approaches building on these advances are used to assemble
      multicellular mimetic-tissues where cells reside within defined spatial contexts.
      The functional responses of cells in fabricated microenvironments have revealed a
      rich interplay between the genome and extracellular effectors in determining
      cellular phenotypes and in a number of cases have revealed the dominance of
      microenvironment over genotype. Precision bioengineered substrata are limited to
      a few aspects, whereas cell/tissue-derived microenvironments have many undefined
      components. Thus, introducing a computational module may serve to integrate these
      types of platforms to create reasonable models of drug responses in human
      tissues. This review discusses how combinatorial microenvironment microarrays and
      other biomimetic microenvironments have revealed emergent properties of cells in
      particular microenvironmental contexts, the platforms that can measure phenotypic
      changes within those contexts, and the computational tools that can unify the
      microenvironment-imposed functional phenotypes with underlying constellations of
      proteins and genes. Ultimately we propose that a merger of these technologies
      will enable more accurate pre-clinical drug discovery. 

PMID- 24582545
TI  - Computerized breast lesions detection using kinetic and morphologic analysis for
      dynamic contrast-enhanced MRI.
AB  - To facilitate rapid and accurate assessment, this study proposed a novel fully
      automatic method to detect and identify focal tumor breast lesions using both
      kinetic and morphologic features from dynamic contrast-enhanced magnetic
      resonance imaging (DCE-MRI). After motion registration of all phases of the DCE
      MRI study, three automatically generated lines were used to segment the whole
      breast region of each slice. The kinetic features extracted from the pixel-based
      time-signal intensity curve (TIC) by a two-stage detection algorithm was first
      used, and then three-dimensional (3-D) morphologic characteristics of the
      detected regions were applied to differentiate between tumor and non-tumor
      regions. In this study, 95 biopsy-confirmed lesions (28 benign and 67 malignant
      lesions) in 54 women were used to evaluate the detection efficacy of the proposed
      system. The detection performance was analyzed using the free-response operating
      characteristics (FROC) curve and detection rate. The proposed computer-aided
      detection (CADe) system had a detection rate of 92.63% (88/95) of all tumor
      lesions, with 6.15 false positives per case. Based on the results, kinetic
      features extracted by TIC can be used to detect tumor lesions and 3-D morphology
      can effectively reduce the false positives.

PMID- 24582546
TI  - DTI-based segmentation and quantification of human brain lateral ventricular CSF
      volumetry and mean diffusivity: validation, age, gender effects and biophysical
      implications.
AB  - The human brain lateral ventricular (LV) cerebrospinal fluid (CSF) volume has
      been used as a neuroimaging marker of brain changes in health and disease. The LV
      CSF diffusivity may offer a useful quality assurance measure and become a
      potential noninvasive marker of deep brain temperature. In this work we sought to
      validate a method for human brain lateral ventricular (LV) cerebrospinal fluid
      (CSF) using diffusion tensor imaging (DTI) contrast to provide LV volume and
      corresponding DTI metrics. We compared LV volume obtained using DTI with that
      obtained using validated segmentations of the LV on T1-weighted data. DTI and T1
      weighted data were acquired at 3T on 49 healthy males and 56 age-matched females
      aged 18-59 years. We showed histogram distributions of LV DTI metrics to
      establish quality assurance measures. We also analyzed the age and gender effects
      of LV volume and diffusivity. LV volumes estimated using both T1-weighted and DTI
      correlated strongly in males and females (ICC=0.99; median Dice index ~80%). The
      LV-to-intracranial volume percentage increased significantly with age only in
      males, using the DTI-based approach (r=0.39; p=0.005). LV CSF Mean diffusivity
      was greater in males than females ((~1.2%; p=0.03). Mean diffusivity of lateral
      ventricular CSF decreased significantly with age in healthy adults (r=-0.30;
      p=0.02). Our results highlight the importance of age and gender-based analyses
      and the potential of LV diffusivity measures as a quantitative marker.

PMID- 24582547
TI  - Diffusion-weighted echo-planar imaging of the head and neck using 3-T MRI:
      Investigation into the usefulness of liquid perfluorocarbon pads and choice of
      optimal fat suppression method.
AB  - PURPOSE: To investigate whether image quality can be improved using liquid
      perfluorocarbon pads (Sat Pad) and clarify the optimal fat-suppression method
      among chemical shift selective (CHESS), water excitation (WEX), and short TI
      inversion recovery (STIR) methods in diffusion-weighted imaging (DWI) of the head
      and neck using 3-T magnetic resonance imaging. Correlations between results of
      visual inspection and quantitative analysis were also examined. MATERIAL AND
      METHODS: This study was approved by our Institutional Review Board and informed
      consent was waived. DWI was performed on 25 subjects with/without Sat Pad and
      using three fat-suppression methods (6 patterns). Image quality was evaluated
      visually (4-point scales and lesion-depiction capability) and by quantitative
      analysis (signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR)). Two-way
      repeated-measures analysis of variance (ANOVA) was used to detect significant
      differences in scores of visual evaluation, SNR, and CNR. RESULTS: Mean visual
      evaluation scores were significantly higher with Sat Pad using STIR than without
      Sat Pad for all fat-suppression methods (P<0.05). DWI with Sat Pad using STIR
      tended to be useful for depicting lesions. DWI using STIR showed reduced W-SNR
      (W: whole area of depicted structure) and CNR (between semispinalis capitis
      muscle and subcutaneous fat) due to fewer artifacts and uniform fat suppression.
      CONCLUSION: Combining Sat Pad with STIR provides good image quality for visual
      inspections. When numerous artifacts are present and fat suppression is
      insufficient, higher SNR and CNR do not always provide good diagnostic image
      quality.

PMID- 24582548
TI  - Dual-source parallel radiofrequency transmission for magnetic resonance breast
      imaging at 3T: any added clinical value?
AB  - PURPOSE: To investigate the influence of dual-source parallel radiofrequency (RF)
      excitation on clinical breast MR images. METHODS: A 3T MR system with both dual
      source and conventional single-source RF excitations was used to examine 22
      patients. Axial TSE-T2WI with fat suppression, TSE-T1WI without fat suppression,
      THRIVE (3D field echo) and DWI (SE-EPI) were obtained by using both excitation
      techniques. Image homogeneity, image contrast and lesion conspicuity were
      measured or independently scored by two radiologists and were compared by paired
      sample t test or Wilcoxon test. RESULTS: Both excitations revealed 24 lesions.
      For SE sequences using dual-source mode, image homogeneity was improved (P=0.00),
      scan time was reduced, and ghost artifacts on DWI were significantly reduced
      (P=0.00). However, image contrast was not increased and lesion conspicuity had no
      significant difference between two modes, except DWI on which lesion conspicuity
      was significantly improved (P=0.00), due to less ghost artifacts. For field-echo
      sequence, image homogeneity, acquisition time, image contrast and lesion
      conspicuity had no significant difference between the two modes. CONCLUSIONS:
      Dual-source parallel RF transmission has some added value for improving breast
      image quality. However, its value is limited in terms of improving lesion
      detection and characterization.

PMID- 24582549
TI  - Neuroprotective effects of the mitochondria-targeted antioxidant MitoQ in a model
      of inherited amyotrophic lateral sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder
      characterized by motor neuron degeneration that ultimately results in progressive
      paralysis and death. Growing evidence indicates that mitochondrial dysfunction
      and oxidative stress contribute to motor neuron degeneration in ALS. To further
      explore the hypothesis that mitochondrial dysfunction and nitroxidative stress
      contribute to disease pathogenesis at the in vivo level, we assessed whether the
      mitochondria-targeted antioxidant [10-(4,5-dimethoxy-2-methyl-3,6-dioxo-1,4
      cyclohexadien-1-yl)decyl]triphenylphosphonium methane sulfonate (MitoQ) can
      modify disease progression in the SOD1(G93A) mouse model of ALS. To do this, we
      administered MitoQ (500 uM) in the drinking water of SOD1(G93A) mice from a time
      when early symptoms of neurodegeneration become evident at 90 days of age until
      death. This regime is a clinically plausible scenario and could be more easily
      translated to patients as this corresponds to initiating treatment of patients
      after they are first diagnosed with ALS. MitoQ was detected in all tested tissues
      by liquid chromatography/mass spectrometry after 20 days of administration. MitoQ
      treatment slowed the decline of mitochondrial function, in both the spinal cord
      and the quadriceps muscle, as measured by high-resolution respirometry.
      Importantly, nitroxidative markers and pathological signs in the spinal cord of
      MitoQ-treated animals were markedly reduced and neuromuscular junctions were
      recovered associated with a significant increase in hindlimb strength. Finally,
      MitoQ treatment significantly prolonged the life span of SOD1(G93A) mice. Our
      results support a role for mitochondrial nitroxidative damage and dysfunction in
      the pathogenesis of ALS and suggest that mitochondria-targeted antioxidants may
      be of pharmacological use for ALS treatment.

PMID- 24582550
TI  - Association between susceptibility to advanced pelvic organ prolapse and
      glutathione S-transferase P1 Ile105Val polymorphism.
AB  - OBJECTIVE: Oxidative stress is associated with the pathogenesis of pelvic organ
      prolapse (POP). Because glutathione S-transferases (GSTs) are the major
      detoxification enzymes which protect cells against oxidative stress, genetic
      variations in the GST gene may modulate the risk of POP. This study aimed to
      determine the association between advanced POP and the polymorphisms of GSTM1,
      GSTT1 and GSTP1 (rs1695). STUDY DESIGN: This is a hospital-based case-control
      study. The POP group consisted of 189 women diagnosed with POP stage III or IV,
      and the control group consisted of 156 postmenopausal women with POP stage 0 or
      I. The GSTM1 and GSTT1 null mutations were detected by multiplex PCR, and the
      GSTP1 Ile105Val polymorphism was genotyped by real-time PCR analysis using a
      TaqMan assay. RESULTS: There was no significant association between the GSTM1 and
      GSTT1 null mutations and advanced POP (p>0.05). The distribution of the GSTP1
      Ile105Val genotypes, however, was significantly different between the POP and
      control groups (AA/AG/GG rates=74.1%/25.9%/0% vs. 64.1%/32.1%/3.8%, p=0.008), and
      the G allele frequency was significantly lower in the POP group than in the
      control group (13.0% vs. 19.9%, p=0.014). Women with the non-AA genotype had a
      0.63-fold lower risk of developing advanced POP than women with the AA genotype
      (95% CI, 0.39-0.99), and women with the G allele had a 0.60-fold lower risk of
      advanced POP than women with the A allele (95% CI, 0.40-0.90). CONCLUSIONS: The
      GSTP1 Ile105Val polymorphism is a protective factor against advanced POP.

PMID- 24582551
TI  - Human NK cell response to pathogens.
AB  - NK cells represent important effectors of the innate immunity in the protection
      of an individual from microbes. During an NK-mediated anti-microbial response,
      the final fate (survival or death) of a potential infected target cell depends
      primarily on the type and the number of receptor/ligand interactions occurring at
      the effector/target immune synapse. The identification of an array of receptors
      involved in NK cell triggering has been crucial for a better understanding of the
      NK cell biology. In this context, NCR play a predominant role in NK cell
      activation during the process of natural cytotoxicity. Regarding the NK-mediated
      pathogen recognition and NK cell activation, an emerging concept is represented
      by the involvement of TLRs and activating KIRs. NK cells express certain TLRs in
      common with other innate cell types. This would mean that specific TLR ligands
      are able to promote the simultaneous and synergistic stimulation of these innate
      cells, providing a coordinated mechanism for regulating the initiation and
      amplification of immune responses. Evidences have been accumulated indicating
      that viral infections may have a significant impact on NK cell maturation,
      promoting the expansion of phenotypically and functionally aberrant NK cell
      subpopulations. For example, during chronic HIV-infection, an abnormal expansion
      of a dysfunctional CD56neg NK cell subset has been detected that may explain, at
      least in part, the defective NK cell-mediated antiviral activity. An analogous
      imbalance of NK cell subsets has been detected in patients receiving HSCT to cure
      high risk leukemias and experiencing HCMV infection/reactivation. Remarkably, NK
      cells developing after CMV reactivation may contain "memory-like" or "long-lived"
      NK cells that could exert a potent anti-leukemia effect. 

PMID- 24582553
TI  - Acceleration of re-endothelialization and inhibition of neointimal formation
      using hybrid biodegradable nanofibrous rosuvastatin-loaded stents.
AB  - Incomplete endothelialization and neointimal hyperplasia of injured arteries can
      cause acute and late stent thromboses. This work develops hybrid
      stent/biodegradable nanofibers for the local and sustained delivery of
      rosuvastatin to denuded artery walls. Biodegradable nanofibers were firstly
      prepared by dissolving poly(D,L)-lactide-co-glycolide and rosuvastatin in
      1,1,1,3,3,3-hexafluoro-2-propanol. The solution was then electrospun into
      nanofibrous tubes, which were mounted onto commercially available bare-metal
      stents. The in vitro release rates of the pharmaceuticals from the nanofibers
      were determined using an elution method and a high-performance liquid
      chromatography assay. The experimental results thus obtained suggest that the
      biodegradable nanofibers released high concentrations of rosuvastatin for four
      weeks. The effectiveness of the local delivery of rosuvastatin in reducing
      platelets was studied. The tissue inflammatory reaction caused by the hybrid
      stents that were used to treat diseased arteries was also documented. The
      proposed hybrid stent/biodegradable rosuvastatin-loaded nanofibers contributed
      substantially to the local and sustainable delivery of a high concentration of
      drugs to promote re-endothelialization, improve endothelial function, reduce
      inflammatory reaction, and inhibit neointimal formation of the injured artery.
      The results of this work provide insight into how patients with a high risk of
      stent restenosis should be treated for accelerating re-endothelialization and
      inhibiting neointimal hyperplasia. 

PMID- 24582552
TI  - Micropattern width dependent sarcomere development in human ESC-derived
      cardiomyocytes.
AB  - In this study, human embryonic stem cell-derived cardiomyocytes were seeded onto
      controlled two-dimensional micropatterned features, and an improvement in
      sarcomere formation and cell alignment was observed in specific feature
      geometries. High-resolution photolithography techniques and microcontact printing
      were utilized to produce features of various rectangular geometries, with areas
      ranging from 2500 MUm(2) to 160,000 MUm(2). The microcontact printing method was
      used to pattern non-adherent poly(ethylene glycol) regions on gold coated glass
      slides. Matrigel and fibronectin extracellular matrix (ECM) proteins were layered
      onto the gold-coated glass slides, providing a controlled geometry for cell
      adhesion. We used small molecule-based differentiation and an antibiotic
      purification step to produce a pure population of immature cardiomyocytes from H9
      human embryonic stem cells (hESCs). We then seeded this pure population of human
      cardiomyocytes onto the micropatterned features of various sizes and observed how
      the cardiomyocytes remodeled their myofilament structure in response to the
      feature geometries. Immunofluorescence was used to measure alpha-actinin
      expression, and phalloidin stains were used to detect actin presence in the
      patterned cells. Analysis of nuclear alignment was also used to determine how
      cell direction was influenced by the features. The seeded cells showed clear
      alignment with the features, dependent on the width rather than the overall
      aspect ratio of the features. It was determined that features with widths between
      30 MUm and 80 MUm promoted highly aligned cardiomyocytes with a dramatic increase
      in sarcomere alignment relative to the long axis of the pattern. This creation of
      highly-aligned cell aggregates with robust sarcomere structures holds great
      potential in advancing cell-based pharmacological studies, and will help
      researchers to understand the means by which ECM geometries can affect
      myofilament structure and maturation in hESC-derived cardiomyocytes. 

PMID- 24582555
TI  - Corrosion and erosion monitoring in plates and pipes using constant group
      velocity Lamb wave inspection.
AB  - Recent improvements in tomographic reconstruction techniques generated a renewed
      interest in short-range ultrasonic guided wave inspection for real-time
      monitoring of internal corrosion and erosion in pipes and other plate-like
      structures. Emerging evidence suggests that in most cases the fundamental
      asymmetric A0 mode holds a distinct advantage over the earlier market leader
      fundamental symmetric S0 mode. Most existing A0 mode inspections operate at
      relatively low inspection frequencies where the mode is highly dispersive
      therefore very sensitive to variations in wall thickness. This paper examines the
      potential advantages of increasing the inspection frequency to the so-called
      constant group velocity (CGV) point where the group velocity remains essentially
      constant over a wide range of wall thickness variation, but the phase velocity is
      still dispersive enough to allow accurate wall thickness assessment from phase
      angle measurements. This paper shows that in the CGV region the crucial issue of
      temperature correction becomes especially simple, which is particularly
      beneficial when higher-order helical modes are also exploited for tomography. One
      disadvantage of working at such relatively high inspection frequency is that, as
      the slower A0 mode becomes faster and less dispersive, the competing faster S0
      mode becomes slower and more dispersive. At higher inspection frequencies these
      modes cannot be separated any longer based on their vibration polarization only,
      which is mostly tangential for the S0 mode while mostly normal for the A0 at low
      frequencies, as the two modes become more similar as the frequency increases.
      Therefore, we propose a novel method for suppressing the unwanted S0 mode based
      on the Poisson effect of the material by optimizing the angle of inclination of
      the equivalent transduction force of the Electromagnetic Acoustic Transducers
      (EMATs) used for generation and detection purposes. 

PMID- 24582554
TI  - The use of cationic MPEG-PCL-g-PEI micelles for co-delivery of Msurvivin T34A
      gene and doxorubicin.
AB  - In our previous study, a series of triblock copolymers based on MPEG-PCL-g-PEI
      were successfully synthesized, and the physicochemical properties of their self
      assembled micelles were also investigated. Here, a further evaluation of these
      micelles was carried out, including in vitro drug release behavior, body
      distribution as well as blood compatibility. The developed MPEG-PCL-g-PEI
      micelles was labeled with (99)Tc for tracing the body distribution of micelles
      after i.v. injection, and the results showed that the MPEG-PCL-g-PEI micelles
      mainly concentrated in the tumor tissue. Meanwhile, the anti-tumor activity on
      both B16F10 subcutaneous tumor model and lung metastasis model was tested and the
      results indicated that DOX-loaded micelles could significantly inhibit tumor
      growth as compared with free doxorubicin, which was accompanied by significantly
      increased apoptosis of tumor cells. By introduction of gene Msurvivin T34A in
      combination with chemotherapies in the treatment of lung metastasis tumor, it
      could greatly reduce systemic toxicity as well as improved the anti-tumor
      efficiency. These results demonstrated that it is possible to use cationic MPEG
      PCL-g-PEI micelles for effectively co-delivering functional gene and
      chemotherapeutic agent, and thus improving anti-tumor effect and systemic
      toxicity. 

PMID- 24582556
TI  - Built-up edge investigation in vibration drilling of Al2024-T6.
AB  - Adding ultrasonic vibrations to drilling process results in an advanced hybrid
      machining process, entitled "vibration drilling". This study presents the design
      and fabrication of a vibration drilling tool by which both rotary and vibrating
      motions are applied to drill simultaneously. High frequency and low amplitude
      vibrations were generated by an ultrasonic transducer with frequency of 19.65
      kHz. Ultrasonic transducer was controlled by a MPI ultrasonic generator with 3 kW
      power. The drilling tool and workpiece material were HSS two-flute twist drill
      and Al2024-T6, respectively. The aim of this study was investigating on the
      effect of ultrasonic vibrations on built-up edge, surface quality, chip
      morphology and wear mechanisms of drill edges. Therefore, these factors were
      studied in both vibration and ordinary drilling. Based on the achieved results,
      vibration drilling offers less built-up edge and better surface quality compared
      to ordinary drilling.

PMID- 24582557
TI  - On the propagation of long thickness-stretch waves in piezoelectric plates.
AB  - We study the propagation of thickness-stretch waves in a piezoelectric plate of
      polarized ceramics with thickness poling or crystals of class 6 mm whose sixfold
      axis is along the plate thickness. For device applications we consider long waves
      with wavelengths much longer than the plate thickness. A system of two
      dimensional equations in the literature governing thickness-stretch, extensional,
      and symmetric thickness-shear motions of the plate is further simplified. The
      equations obtained can be used to analyze piezoelectric plate acoustic wave
      devices operating with thickness-stretch modes. 

PMID- 24582558
TI  - Interleukin 6 promotes endometrial cancer growth through an autocrine feedback
      loop involving ERK-NF-kappaB signaling pathway.
AB  - Interleukin (IL)-6 as an inflammation factor, has been proved to promote cancer
      proliferation in several human cancers. However, its role in endometrial cancer
      has not been studied clearly. Previously, we demonstrated that IL-6 promoted
      endometrial cancer progression through local estrogen biosynthesis. In this
      study, we proved that IL-6 could directly stimulate endometrial cancer cells
      proliferation and an autocrine feedback loop increased its production even after
      the withdrawal of IL-6 from the medium. Next, we analyzed the mechanism
      underlying IL-6 production in the feedback loop and found that its production and
      IL-6-stimulated cell proliferation were effectively blocked by pharmacologic
      inhibitors of nuclear factor-kappa B (NF-kappaB) and extra-cellular signal
      regulated kinase (ERK). Importantly, activation of ERK was upstream of the NF
      kappaB pathways, revealing the hierarchy of this event. Finally, we used an
      orthotopic nude endometrial carcinoma model to confirm the effects of IL-6 on the
      tumor progression. Taken together, these data indicate that IL-6 promotes
      endometrial carcinoma growth through an expanded autocrine regulatory loop and
      implicate the ERK-NF-kappaB pathway as a critical mediator of IL-6 production,
      implying IL-6 to be an important therapeutic target in endometrial carcinoma. 

PMID- 24582559
TI  - Ethanol-induced impairment of polyamine homeostasis--a potential cause of neural
      tube defect and intrauterine growth restriction in fetal alcohol syndrome.
AB  - INTRODUCTION: Polyamines play a fundamental role during embryogenesis by
      regulating cell growth and proliferation and by interacting with RNA, DNA and
      protein. The polyamine pools are regulated by metabolism and uptake from
      exogenous sources. The use of certain inhibitors of polyamine synthesis causes
      similar defects to those seen in alcohol exposure e.g. retarded embryo growth and
      endothelial cell sprouting. METHODS: CD-1 mice received two intraperitoneal
      injections of 3 g/kg ethanol at 4 h intervals 8.75 days post coitum (dpc). The
      fetal head, trunk, yolk sac and placenta were collected at 9.5 and 12.5 dpc and
      polyamine concentrations were determined. RESULTS: No measurable quantity of
      polyamines could be detected in the embryo head at 9.5 dpc, 12 h after ethanol
      exposure. Putrescine was not detectable in the trunk of the embryo at that time,
      whereas polyamines in yolk sac and placenta were at control level. Polyamine
      deficiency was associated with slow cell growth, reduction in endothelial cell
      sprouting, an altered pattern of blood vessel network formation and consequently
      retarded migration of neural crest cells and growth restriction. DISCUSSION: Our
      results indicate that the polyamine pools in embryonic and extraembryonic tissues
      are developmentally regulated. Alcohol administration, at the critical stage,
      perturbs polyamine levels with various patterns, depending on the tissue and its
      developmental stage. The total absence of polyamines in the embryo head at 9.5
      dpc may explain why this stage is so vulnerable to the development of neural tube
      defect, and growth restriction, the findings previously observed in fetal alcohol
      syndrome.

PMID- 24582560
TI  - HMG-CoA reductase regulates CCL17-induced colon cancer cell migration via
      geranylgeranylation and RhoA activation.
AB  - BACKGROUND: Simvastatin is widely used to lower cholesterol levels in patients
      with cardiovascular diseases, although accumulating evidence suggests that
      statins, such as simvastatin, also exert numerous anti-tumoral effects. AIM: The
      aim of this study was to examine the effect of simvastatin on colon cancer cell
      migration. METHODS: Migration assays were performed to evaluate CCL17-induced
      colon cancer cell (HT-29) chemotaxis. In vitro tumor growth and apoptosis were
      assessed using a proliferation assay and annexin V assay, respectively. Active
      RhoA protein levels in CCL17-stimulated colon cancer cells were quantified using
      a G-LISA assay. RESULTS: We found that simvastatin dose-dependently decreased
      CCL17-induced colon cancer cell migration. Simvastatin had no effect on colon
      cancer cell proliferation or apoptosis. Inhibition of beta chemokine receptor 4,
      CCR4, reduced CCL17-evoked activation of RhoA in colon cancer cells. Moreover,
      administration of mevalonate reversed the inhibitory effect of simvastatin on
      CCL17-induced colon cancer cell migration. Interestingly, co-incubation with
      geranylgeranyl pyrophosphate (GGPP) antagonized the inhibitory impact of
      simvastatin on colon cancer cell migration triggered by CCL17. Moreover, we
      observed that simvastatin decreased CCL17-induced activation of RhoA in colon
      cancer cells. Administration of mevalonate and GGPP reversed the inhibitory
      effect of simvastatin on CCL17-provoked RhoA activation in colon cancer cells.
      CONCLUSIONS: Taken together, our findings show for the first time that HMG-CoA
      reductase regulates CCL17-induced colon cancer cell migration via inhibition of
      geranylgeranylation and RhoA activation. Thus, statins, such as simvastatin,
      might be effective tools to antagonize CCL17-dependent migration and metastasis
      of colon cancer cells.

PMID- 24582561
TI  - Nuclear translocation of doublecortin-like protein kinase and phosphorylation of
      a transcription factor JDP2.
AB  - Doublecortin-like protein kinase (DCLK) is a microtubule-associated protein
      kinase predominantly expressed in brain. In a previous paper, we reported that
      zebrafish DCLK2 (zDCLK) was cleaved into two functional fragments; the N-terminal
      zDCLK(DC+SP) with microtubule-binding activity and the C-terminal zDCLK(kinase)
      with a Ser/Thr protein kinase activity. In this study, we demonstrated that
      zDCLK(kinase) was widely distributed in the cytoplasm and translocated into the
      nucleus when the cells were treated under hyperosmotic conditions with NaCl or
      mannitol. By two-hybrid screening using the C-terminal domain of DCLK, Jun
      dimerization protein 2 (JDP2), a nuclear transcription factor, was identified as
      zDCLK(kinase)-binding protein. Furthermore, JDP2 served as an efficient substrate
      for zDCLK(kinase) only when histone was present. These results suggest that the
      kinase fragment of DCLK is translocated into the nucleus upon hyperosmotic
      stresses and that the kinase efficiently phosphorylates JDP2, a possible target
      in the nucleus, with the aid of histones. 

PMID- 24582562
TI  - The Hsp90 inhibitor SNX-2112 induces apoptosis of human hepatocellular carcinoma
      cells: the role of ER stress.
AB  - Heat shock protein 90 (Hsp90) has been predicted to be involved in hepatocellular
      carcinoma (HCC) therapy; however, the mechanisms of action remain elusive. SNX
      2112 is an Hsp90 inhibitor showing broad antitumor activity. Here we aim to
      determine the role of the endoplasmic reticulum (ER) stress in SNX-2112-induced
      apoptosis in HCC cells. In general, three HCC cells (i.e., HepG2, Huh7, and SK
      Hep1) were used in our experiments. The cell viability was determined by the CCK
      8 assay. The apoptosis was analyzed using flow cytometry, laser scanning confocal
      microscopy (LSM) and Western blotting. The efficacy and mechanisms of action of
      SNX-2112 were also evaluated in a mouse xenograft model. We found that SNX-2112
      showed stronger inhibition on cell growth than 17-AAG, a classical Hsp90
      inhibitor. SNX-2112 treatment led to the caspase-dependent apoptosis.
      Interestingly, SNX-2112 decreased the expression levels of the ER chaperone
      proteins calnexin and immunoglobulin binding protein (BiP). It also inhibited all
      three ER stress sensors, namely, inositol-requiring gene 1 (IRE1), PKR-like ER
      kinase (PERK), and activating transcription factor 6 (ATF-6) in vitro and/or in
      vivo. However, the ER stress inducer tunicamycin strongly enhanced SNX-2112
      induced apoptosis, whereas the IRE1 knockdown did not. Taken together, we for the
      first time indicated the possible apoptotic pathways of SNX-2112 in HCC cells,
      raising the possibility that the induction of ER stress might be favorable for
      SNX-2112-induced apoptosis. 

PMID- 24582563
TI  - Biological activities of Schottenol and Spinasterol, two natural phytosterols
      present in argan oil and in cactus pear seed oil, on murine miroglial BV2 cells.
AB  - The objective of this study was to evaluate the biological activities of the
      major phytosterols present in argan oil (AO) and in cactus seed oil (CSO) in BV2
      microglial cells. Accordingly, we first determined the sterol composition of AO
      and CSO, showing the presence of Schottenol and Spinasterol as major sterols in
      AO. While in CSO, in addition to these two sterols, we found mainly another
      sterol, the Sitosterol. The chemical synthesis of Schottenol and Spinasterol was
      performed. Our results showed that these two phytosterols, as well as sterol
      extracts from AO or CSO, are not toxic to microglial BV2 cells. However,
      treatments by these phytosterols impact the mitochondrial membrane potential.
      Furthermore, both Schottenol and Spinasterol can modulate the gene expression of
      two nuclear receptors, liver X receptor (LXR)-alpha and LXRbeta, their target
      genes ABCA1 and ABCG1. Nonetheless, only Schottenol exhibited a differential
      activation vis-a-vis the nuclear receptor LXRbeta. Thus Schottenol and
      Spinasterol can be considered as new LXR agonists, which may play protective
      roles by the modulation of cholesterol metabolism. 

PMID- 24582564
TI  - Tumor endothelial expression of P-glycoprotein upon microvesicular transfer of
      TrpC5 derived from adriamycin-resistant breast cancer cells.
AB  - Treatment of carcinoma commonly fails due to chemoresistance. Studies have shown
      that endothelial cells acquire resistance via the tumor microenvironment.
      Microvesicle (MV) shedding from the cell membrane to the microenvironment plays
      an important role in communication between cells. The aim of the present study
      was to determine whether MCF-7 adriamycin-resistant cells (MCF-7/ADM) shed MVs
      that alter the characteristics of human microvessel endothelial cells (HMECs).
      MVs from tumor cells transferred a Ca(2+)-permeable channel TrpC5 to HMECs,
      inducing the expression of P-glycoprotein (P-gp) by activation of the
      transcription factor NFATc3 (nuclear factor of activated T cells isoform c3).
      Expression of the mdr1 gene was blocked by the TrpC5-blocking antibody T5E3, and
      the production of P-gp in HMECs was reduced by blockade of TrpC5. Thus, we
      postulate that endothelial cells acquire the resistant protein upon exposure to
      TrpC5-containg MVs in the microenvironment, and express P-gp in the TrpC5-NFATc3
      signal pathway. 

PMID- 24582565
TI  - Globular adiponectin induces a pro-inflammatory response in human astrocytic
      cells.
AB  - Neuroinflammation, mediated in part by activated brain astrocytes, plays a
      critical role in the development of neurodegenerative disorders, including
      Alzheimer's disease (AD). Adiponectin is the most abundant adipokine secreted
      from adipose tissue and has been reported to exert both anti- and pro
      inflammatory effects in peripheral tissues; however, the effects of adiponectin
      on astrocytes remain unknown. Shifts in peripheral concentrations of adipokines,
      including adiponectin, could contribute to the observed link between midlife
      adiposity and increased AD risk. The aim of the present study was to characterize
      the effects of globular adiponectin (gAd) on pro-inflammatory cytokine mRNA
      expression and secretion in human U373 MG astrocytic cells and to explore the
      potential involvement of nuclear factor (NF)-kappaB, p38 mitogen-activated
      protein kinase (MAPK), extracellular signal-regulated kinase (ERK)1/2, c-Jun N
      terminal kinase (JNK) and phosphatidylinositide 3-kinases (PI3K) signaling
      pathways in these processes. We demonstrated expression of adiponectin receptor 1
      (adipoR1) and adipoR2 in U373 MG cells and primary human astrocytes. gAd induced
      secretion of interleukin (IL)-6 and monocyte chemoattractant protein (MCP)-1, and
      gene expression of IL-6, MCP-1, IL-1beta and IL-8 in U373 MG cells. Using
      specific inhibitors, we found that NF-kappaB, p38MAPK and ERK1/2 pathways are
      involved in gAd-induced induction of cytokines with ERK1/2 contributing the most.
      These findings provide evidence that gAd may induce a pro-inflammatory phenotype
      in human astrocytes. 

PMID- 24582566
TI  - How can we rationally select Helicobacter pylori therapy without resistance data?

PMID- 24582567
TI  - Resveratrol does not benefit patients with nonalcoholic fatty liver disease.
AB  - BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD), characterized by
      accumulation of hepatic triglycerides (steatosis), is associated with abdominal
      obesity, insulin resistance, and inflammation. Although weight loss via calorie
      restriction reduces features of NAFLD, there is no pharmacologic therapy.
      Resveratrol is a polyphenol that prevents high-energy diet-induced steatosis and
      insulin resistance in animals by up-regulating pathways that regulate energy
      metabolism. We performed a placebo-controlled trial to assess the effects of
      resveratrol in patients with NAFLD. METHODS: Overweight or obese men diagnosed
      with NAFLD were recruited from hepatology outpatient clinics in Brisbane,
      Australia from 2011 through 2012. They were randomly assigned to groups given
      3000 mg resveratrol (n = 10) or placebo (n = 10) daily for 8 weeks. Outcomes
      included insulin resistance (assessed by the euglycemic-hyperinsulinemic clamp),
      hepatic steatosis, and abdominal fat distribution (assessed by magnetic resonance
      spectroscopy and imaging). Plasma markers of inflammation, as well as metabolic,
      hepatic, and antioxidant function, were measured; transcription of target genes
      was measured in peripheral blood mononuclear cells. Resveratrol pharmacokinetics
      and safety were assessed. RESULTS: Eight-week administration of resveratrol did
      not reduce insulin resistance, steatosis, or abdominal fat distribution when
      compared with baseline. No change was observed in plasma lipids or antioxidant
      activity. Levels of alanine and aspartate aminotransferases increased
      significantly among patients in the resveratrol group until week 6 when compared
      with the placebo group. Resveratrol did not significantly alter transcription of
      NQO1, PTP1B, IL6, or HO1 in peripheral blood mononuclear cells. Resveratrol was
      well-tolerated. CONCLUSIONS: Eight weeks administration of resveratrol did not
      significantly improve any features of NAFLD, compared with placebo, but it
      increased hepatic stress, based on observed increases in levels of liver enzymes.
      Further studies are needed to determine whether agents that are purported to
      mimic calorie restriction, such as resveratrol, are safe and effective for
      complications of obesity. Clinical trials registration no: ACTRN12612001135808.

PMID- 24582568
TI  - Increased risk of acute myeloid leukemias and myelodysplastic syndromes in
      patients who received thiopurine treatment for inflammatory bowel disease.
AB  - BACKGROUND & AIMS: Treatment with immunosuppressive thiopurines such as
      azathioprine is associated with an increased risk of leukemogenesis. We assessed
      the risk of myeloid disorders, such as acute myeloid leukemia and myelodysplastic
      syndromes, in a large cohort of patients with inflammatory bowel disease (IBD) in
      France. METHODS: We performed a prospective observational study of 19,486
      patients with IBD enrolled in the Cancers Et Surrisque Associe aux Maladies
      inflammatoires intestinales En France (CESAME) study from May 2004 through June
      2005; patients were followed through December 31, 2007. The incidence of myeloid
      disorders in the general population, which was used for reference, was determined
      from the French Network of Cancer Registries. RESULTS: During 49,736 patient
      years of follow-up, 5 patients were diagnosed with incident myeloid disorders (2
      with acute myeloid leukemia and 3 with myelodysplastic syndromes). Four of these
      patients had been exposed to thiopurines (1 with ongoing treatment and 3 with
      past exposure). The risk of myeloid disorders was not increased among the overall
      IBD population, compared with the general population; the standardized incidence
      ratio (SIR) was 1.80 (95% confidence interval [CI], 0.58-4.20). The risk of
      myeloid disorders was not increased among patients with IBD and ongoing
      thiopurine treatment (SIR, 1.54; 95% CI, 0.05-8.54), but patients with past
      exposures to thiopurines had an increased risk of myeloid disorders (SIR, 6.98;
      95% CI, 1.44-20.36). CONCLUSIONS: Past exposure to thiopurines increases the risk
      of myeloid disorders 7-fold among patients with IBD. This finding should be
      considered when initiating thiopurine therapy, so risks and benefits can be
      calculated.

PMID- 24582570
TI  - Can capsule colonoscopy and computed tomographic colonography accurately evaluate
      patients with positive results from the fecal immunochemical test, and are these
      ready for prime time?

PMID- 24582569
TI  - Effects of polymorphisms in interferon lambda 3 (interleukin 28B) on sustained
      virologic response to therapy in patients with chronic hepatitis D virus
      infection.
AB  - BACKGROUND & AIMS: We investigated the association between interferon lambda 3
      (IFNL3) genotype (also known as interleukin 28B) and response to IFNalpha therapy
      in patients with chronic hepatitis D virus (HDV) infection. METHODS: We studied
      IFNL3 genotypes of 32 patients (19 men; median age, 42.5 y) with chronic HDV
      infection. Nineteen patients (59%) were treated with pegylated IFNalpha and 13
      patients (41%) were treated with standard IFNalpha, for at least 12 months.
      Levels of HDV RNA were measured before the initiation of treatment and every 6
      months thereafter; patients were followed up for a median time of 16 months
      (range, 6-164 mo) after treatment ended. We used real-time polymerase chain
      reaction to classify the IFNL3 polymorphism rs12979860 as CC, CT, or TT, and
      rs8099917 as TT, GT, or GG. A virologic response was defined as undetectable HDV
      RNA in serum, and a sustained virologic response (SVR) was defined as
      undetectable HDV RNA after cessation of treatment until the end of the follow-up
      period. We evaluated the association between IFNL3 polymorphism and treatment
      response using univariate and multivariate analyses. RESULTS: After treatment, a
      response was achieved in 16 patients (50%) and an SVR was achieved in 9 (28%).
      The percentages of patients with CC, CT, and TT at rs12979860 were 47%, 47%, and
      6%, respectively; the percentages of patients with TT, GT, and GG at rs8099917
      were 69%, 28%, and 3%, respectively. Rates of SVR were 27%, 27%, and 50% in
      patients with CC, CT, TT at rs12979860 (P = .78 for CC vs CT vs TT) and 36%, 11%,
      and 0% in patients with TT, GT, and GG at rs8099917 (P = .30 for TT vs GT vs GG).
      CONCLUSIONS: The IFNL3 polymorphisms rs12979860 and rs8099917 do not
      significantly affect responses of patients with chronic HDV infection to
      treatment with IFNalpha.

PMID- 24582571
TI  - Congenital genitourinary abnormalities in children with Williams-Beuren syndrome.
AB  - OBJECTIVE: Williams-Beuren syndrome (WBS) is an autosomal dominant disorder
      caused by a gene deletion on chromosome 7q11.23. Patients with WBS usually show a
      group of features such as developmental delay, cardiovascular anomalies, mental
      retardation, and characteristic facial appearance. Abdominal wall defects,
      external genitalia anomalies, and structural abnormalities of the urinary tract
      have been scarcely evaluated and were the focus of our study. MATERIALS AND
      METHODS: We prospectively evaluated 41 boys and 38 girls with WBS, with a mean
      age of 8.8 +/- 4.1 (range 3-19 years). All patients were examined for the
      evaluation of inguinal and umbilical hernias and genital anomalies. All patients
      were offered a radiological evaluation, including urinary tract ultrasound,
      voiding cystourethrogram, and dimercaptosuccinic acid renal scintigraphy (DMSA
      scan). RESULTS: Of the 41 boys, 30 (73.1%) had abnormalities on physical
      examination, including bilateral undescended testis in 13 (31.7%), retractile
      testis in four (9.7%), hypospadias in four (9.7%), and unilateral cryptorchidism
      in three (7.3%) patients. Of the 38 female subjects, 17 (44.7%) had at least one
      abnormality, including umbilical hernia in 11 (28.9%), unilateral inguinal hernia
      in four (10.5%), and bilateral inguinal hernia in three (7.8%) patients.
      Uroradiological abnormalities were found in 41 patients (51.9%). On sonography,
      six (7.6%) patients had unilateral hydronephrosis, three (3.8%) had a duplicated
      collecting system, and two (2.5%) had kidney stones. On DMSA, performed in 36
      patients, four (11.1%) had unilateral renal scarring and two (5.5%) had bilateral
      renal scarring. Cystourethrography was obtained from 56 patients, of whom 27
      (48.2%) had bladder diverticulum, 18 (32.1%) had bladder wall trabeculation, and
      three (5.3%) had vesicoureteral reflux. We found no association of urological
      abnormalities with cardiovascular defects. CONCLUSIONS: Patients with WBS have a
      high prevalence of abdominal wall, external genitalia, and urological
      abnormalities, emphasizing the importance of proper physical examination and
      radiological investigation in this population.

PMID- 24582572
TI  - Microglial cells in organotypic cultures of developing and adult mouse retina and
      their relationship with cell death.
AB  - Organotypic cultures of retinal explants allow the detailed analysis of
      microglial cells in a cellular microenvironment similar to that in the in situ
      retina, with the advantage of easy experimental manipulation. However, the in
      vitro culture causes changes in the retinal cytoarchitecture and induces a
      microglial response that may influence the results of these manipulations. The
      purpose of this study was to analyze the influence of the retinal age on changes
      in retinal cytoarchitecture, cell viability and death, and microglial phenotype
      and distribution throughout the in vitro culture of developing and adult retina
      explants. Explants from developing (3 and 10 postnatal days, P3 and P10) and
      adult (P60) mouse retinas were cultured for up to 10 days in vitro (div). Dead or
      dying cells were recognized by TUNEL staining, cell viability was determined by
      flow cytometry, and the numbers and distribution patterns of microglial cells
      were studied by flow cytometry and immunocytochemistry, respectively. The retinal
      cytoarchitecture was better preserved at prolonged culture times (10 div) in P10
      retina explants than in P3 or adult explants. Particular patterns of cell
      viability and death were observed at each age: in general, explants from
      developing retinas showed higher cell viability and lower density of TUNEL
      positive profiles versus adult retinas. The proportion of microglial cells
      relative to the whole population of retinal cells was higher in explants fixed
      immediately after their dissection (i.e., non-cultured) from adult retinas than
      in those from developing retinas. This proportion was always higher in non
      cultured explants than in explants at 10 div, suggesting the death of some
      microglial cells during the culture. Activation of microglial cells, as revealed
      by their phenotypical appearance, was observed in both developing and adult
      retina explants from the beginning of the culture. Immunofluorescence with the
      anti-CD68 antibody showed that some activated microglial cells were CD68-positive
      but others were CD68-negative. Flow cytometry using CD68-labeling revealed that
      the percentage of CD68-positive microglial cells was much higher in developing
      than in adult retina explants, despite the activation of microglia in both types
      of explants, indicating that CD68-labeling was more closely related to the
      maturity degree of microglia than to their activation. Some swollen activated
      microglial cells entered the outer nuclear layer in developing and adult cultured
      retinal explants, whereas this layer was devoid of microglia in non-cultured
      explants. There was no apparent correlation between the distribution of microglia
      and that of TUNEL-labeled profiles. However, some swollen activated microglial
      cells in the outer and inner nuclear layers engulfed clusters of cell nuclei that
      were negative or weakly positive for TUNEL. This engulfment activity of microglia
      mimicked that observed in degenerative pathologies of the retina. We conclude
      that organotypic cultures from developing retinas show a higher rate of cell
      viability and better preservation of the normal cytoarchitecture in comparison to
      those obtained from adult retinas. In addition, the features of microglial
      response in cultured retinal explants show them to be a useful model for studying
      interactions between microglial cells and degenerating neurons in retinal
      diseases. 

PMID- 24582574
TI  - Regulation of pluripotent cell differentiation by a small molecule,
      staurosporine.
AB  - Research in the embryo and in culture has resulted in a sophisticated
      understanding of many regulators of pluripotent cell differentiation. As a
      consequence, protocols for the differentiation of pluripotent cells generally
      rely on a combination of exogenous growth factors and endogenous signalling.
      Little consideration has been given to manipulating other pathways to achieve
      pluripotent cell differentiation. The integrity of cell:cell contacts has been
      shown to influence lineage choice during pluripotent cell differentiation, with
      disruption of cell:cell contacts promoting mesendoderm formation and maintenance
      of cell:cell contacts resulting in the preferential formation of neurectoderm.
      Staurosporine is a broad spectrum inhibitor of serine/threonine kinases which has
      several effects on cell function, including interruption of cell:cell contacts,
      decreasing focal contact size, inducing epithelial to mesenchyme transition (EMT)
      and promoting cell differentiation. The possibility that staurosporine could
      influence lineage choice from pluripotent cells in culture was investigated. The
      addition of staurosporine to differentiating mouse EPL resulted in preferential
      formation of mesendoderm and mesoderm populations, and inhibited the formation of
      neurectoderm. Addition of staurosporine to human ES cells similarly induced
      primitive streak marker gene expression. These data demonstrate the ability of
      staurosporine to influence lineage choice during pluripotent cell differentiation
      and to mimic the effect of disrupting cell:cell contacts. Staurosporine induced
      mesendoderm in the absence of known inducers of formation, such as serum and
      BMP4. Staurosporine induced the expression of mesendoderm markers, including
      markers that were not induced by BMP4, suggesting it acted as a broad spectrum
      inducer of molecular gastrulation. This approach has identified a small molecule
      regulator of lineage choice with potential applications in the commercial
      development of ES cell derivatives, specifically as a method for forming
      mesendoderm progenitors or as a culture adjunct to prevent the formation of
      ectoderm progenitors during pluripotent cell differentiation. 

PMID- 24582575
TI  - Generation of induced pluripotent stem cells from neonatal mouse cochlear cells.
AB  - The sensory epithelium (SE) within the mammalian cochleae has a limited capacity
      for regeneration, and the loss of mammalian cochlear hair cells always lead to
      permanent hearing loss. Previous reports show that early postnatal cochlea
      harbors stem/progenitor-like cells nominated otospheres which have a limited
      regenerative/repair capacity, while these cell populations are progressively lost
      during the postnatal development. Induced pluripotent stem cells (iPS cells)
      directly reprogrammed from non-embryonic cells have captured great attentions in
      the scientific community. In the present study, we determine whether Yamanaka's
      factors can induce the reprogramming of cochlear cells into iPS cells. We
      introduce defined factors Oct3/4, Sox2 and Klf4 into otospheres derived from
      postnatal day-1 (P1) mouse SE, and analyze characteristics alterations in
      cochlear cells. After transduction, otospheres generated colonies exhibiting a
      normal karyotype and morphology similar to that of mouse embryonic stem cells
      (ESCs). Moreover, these cochlear iPS cells also express ESC-like markers.
      Importantly, the cochlear iPS cells show pluripotency in vitro and in vivo, as
      evidenced by differentiation into three germ layers by embryoid body formation,
      as well as high efficient formation of teratomas containing three germ layers in
      immunodeficient mice. Thus, pluripotent cochlear iPS cells can be generated from
      cochlear cells by using three Yamanaka's transcription factors. These attempts
      represent the first step toward generating fully pluripotent iPS cells from
      mammalian cochleae with defined exogenous genes. 

PMID- 24582573
TI  - Development of the external genitalia: perspectives from the spotted hyena
      (Crocuta crocuta).
AB  - This review/research paper summarizes data on development of the external
      genitalia of the spotted hyena, a fascinating mammal noted for extreme
      masculinization of the female external genitalia. The female spotted hyena is the
      only extant mammal that mates and gives birth through a pendulous penis-like
      clitoris. Our studies indicate that early formation of the phallus in both males
      and females is independent of androgens; indeed the phallus forms before the
      fetal testes or ovaries are capable of synthesizing androgens. Likewise, pre- and
      postnatal growth in length of the penis and clitoris is minimally affected by
      "androgen status". Nonetheless, several internal morphologies, as well as
      external surface features of the phallus, are androgen-dependent and thus account
      for dimorphism between the penis and clitoris. Finally, estrogens play a critical
      role in penile and clitoral development, specifying the position of the urethral
      orifice, determining elasticity of the urethral meatus, and facilitating
      epithelial-epithelial fusion events required for proper formation of the distal
      urethra/urogenital sinus and prepuce. Accordingly, prenatal inhibition of
      estrogen synthesis via administration of letrozole (an aromatase inhibitor) leads
      to malformations of the glans as well as the prepuce (hypospadias). The effects
      of prenatal androgens, anti-androgens and impaired estrogen synthesis correlated
      with the tissue expression of androgen and estrogen receptors. 

PMID- 24582576
TI  - Molecular characterization of foodborne-associated Staphylococcus aureus strains
      isolated in Shijiazhuang, China, from 2010 to 2012.
AB  - Staphylococcus aureus is an opportunistic pathogen commonly identified from food
      poisoning-associated foodstuffs. From 1996 to the present, S. aureus isolates
      have been found to exhibit increasing resistance to antimicrobial drugs. The aim
      of this study was to assess the molecular epidemiology properties of various S.
      aureus isolates through molecular typing and to investigate their
      characterization based on their production of enterotoxins and hemolysins and
      their resistance to antibiotics. A total of 78 coagulase-positive staphylococcal
      strains isolated from food or clinical samples were analyzed. Eight VNTR loci
      were used to genotype the 78 isolates, and this analysis resulted in 39 different
      multilocus variable number tandem repeat analysis (MLVA) profiles. The isolates
      recovered from a single outbreak exhibited the same MLVA profile. According to
      CLSI, 97.4% of the isolates were resistant to penicillin, whereas only 3.8% were
      methicillin-resistant Staphylococcus aureus strains. Through multiplex PCR, 87.2%
      of the isolates were shown to be enterotoxigenic (SEs), and the most common genes
      present were sea, sem, seg, seu, and sek. In conclusion, this study demonstrates
      the prevalence of staphylococcal enterotoxins, the contents of virulent factors,
      and the characteristics of beta-lactam antibiotic resistance in 78 S. aureus
      isolates. These findings emphasize the need to prevent the presence of S. aureus
      strains and SE production in foods. Our results also demonstrate that MLVA is a
      useful and powerful method for epidemiological studies of S. aureus. In contrast
      to multilocus sequence typing, the MLVA method is a simpler and more rapid method
      for epidemiological typing with a higher discriminatory power. 

PMID- 24582577
TI  - The clinical utility of a near patient care rapid microarray-based diagnostic
      test for influenza and respiratory syncytial virus infections in the pediatric
      setting.
AB  - We evaluated the potential clinical utility of an automated near patient
      molecular assay Verigene Respiratory Virus Plus (RV+) and rapid
      immunochromatographic antigen tests (RIAT) in the pediatric setting for diagnosis
      of influenza and respiratory syncytial virus infections when testing was
      performed by the pediatrician seeing the patient. Overall, with respect to
      influenza virus, sensitivity and specificity for RIAT were 70.8% and 100%,
      respectively, compared to 100% and 96.2%, respectively, for RV+. For respiratory
      syncytial virus, sensitivity and specificity for RIAT were 78.9% and 100%,
      respectively, compared to 100% and 100%, respectively, for RV+. When RIAT and RV+
      sensitivity for influenza virus was compared based on the time the patient
      presented after onset of fever, the sensitivity of RIAT at 6 hours was 37.5%
      compared to 100% for RV+. At 12 hours, RIAT improved to 60.9%. This study
      confirms the clinical utility of RV+ in the pediatric setting. 

PMID- 24582578
TI  - Ceftaroline activity against organisms isolated from respiratory tract infections
      in USA hospitals: results from the AWARE Program, 2009-2011.
AB  - The Assessing Worldwide Antimicrobial Resistance Evaluation Program monitors the
      activity of ceftaroline and comparator agents tested against pathogens causing
      either respiratory or skin and soft tissue infections. A total of 7733 isolates
      from patients in 80 medical centers across the United States (USA) identified as
      respiratory tract pathogens by the infection type and/or specimen site recorded
      by the submitting laboratory during 2009-2011 were evaluated. There were 3360
      isolates of Streptococcus pneumoniae, 1799 Haemophilus influenzae, 1087
      Staphylococcus aureus, 678 Moraxella catarrhalis, 459 Klebsiella pneumoniae, 223
      Escherichia coli, and 127 Klebsiella oxytoca. Annual penicillin resistance among
      S. pneumoniae ranged from 21.9 to 24.3%. All S. pneumoniae strains were inhibited
      at a ceftaroline MIC of <=0.5 MUg/mL with 100.0% of isolates categorized as
      susceptible. Ceftaroline was 16-fold more active than ceftriaxone and 32-fold
      more active than amoxicillin-clavulanate against penicillin-resistant
      pneumococci. Only 49.8% of the penicillin-resistant isolates were susceptible to
      ceftriaxone. There were a total of 1087 S. aureus (48.9% methicillin-resistant S.
      aureus [MRSA]) isolates, and the yearly MRSA rate ranged from 47.9 to 49.7%. The
      ceftaroline MIC50/90 for S. aureus was at 0.25/1 MUg/mL; 98.2% susceptible and no
      resistant strains (>=4 MUg/mL). Ceftaroline activity against methicillin
      susceptible S. aureus (MSSA) isolates (MIC50 and MIC90, 0.25 and 0.25 MUg/mL,
      respectively; 100% susceptible) was 2- to 4-fold greater than for MRSA (MIC50/90,
      0.5/1 MUg/mL; 96.2% susceptible). The ceftriaxone MIC90 for MSSA was 4 MUg/mL.
      Ceftaroline was active against H. influenzae (MIC50/90 <=0.015/0.03 MUg/mL;
      100.0% susceptible) and against M. catarrhalis (MIC50/90, 0.06/0.12 MUg/mL).
      Ceftaroline was active against non-extended spectrum beta-lactamase (ESBL)
      phenotype strains of Enterobacteriaceae but not against ESBL-positive phenotype
      strains. In summary, ceftaroline was highly active against a large collection of
      bacterial pathogens isolated from patients with respiratory tract infections in
      the USA during 2009 through 2011. 

PMID- 24582579
TI  - Muscular abscess caused by Cupriavidus gilardii in a renal transplant recipient.
AB  - Cupriavidus gilardii is a rare cause of human infection. We report a muscular
      abscess on the right thigh caused by this organism in a renal transplant
      recipient, who had suffered a septic shock associated with an extensive
      cellulitis caused by Streptococcus pyogenes. The patient was successfully treated
      with surgical drainage and intravenous ciprofloxacin for 13 days. This is the
      first time that C. gilardii is isolated from a human abscess. C. gilardii should
      be considered as a cause of human infection, especially in immunocompromised
      patients. Infection caused by this organism may be underdiagnosed because the
      identification is very difficult. 

PMID- 24582580
TI  - In vitro activity of tigecycline against isolates collected from complicated skin
      and skin structure infections and intra-abdominal infections in Africa and Middle
      East countries: TEST 2007-2012.
AB  - Complicated skin and skin structure infections (cSSSIs) and intra-abdominal
      infections (IAIs) are problematic due to decreasing therapeutic options available
      against multidrug-resistant pathogens common among these types of infections. A
      total of 2245 isolates from African and the Middle Eastern (AfME) countries were
      collected to determine in vitro activity for tigecycline and comparators during
      2007-2012 as part of the Tigecycline Evaluation Surveillance Trial program.
      Tigecycline was launched in the AfME in 2007 and remains active against a wide
      range of targeted pathogens worldwide. Isolates were recovered from cSSSI (1990)
      and IAI (255) from 38 sites in 11 AfME countries. Staphylococcus aureus was the
      most common species from cSSSI (27.9%), and the methicillin-resistant S. aureus
      rate was 25%. Enterococcus spp. (7.1%) and Streptococcus agalactiae (2.9%) were
      other common Gram-positive pathogens represented. Enterobacter spp. (14.5%),
      Pseudomonas aeruginosa (13.9%), Escherichia coli (11.4%), Klebsiella spp.
      (10.9%), and Acinetobacter spp. (7.2 %) were the most common Gram-negative
      species collected. Tigecycline MIC(90) values were 0.25 MUg/mL against S. aureus.
      E. coli and Enterobacter spp. had tigecycline MIC(90) values of 1 and 2 MUg/mL,
      respectively. E. coli was the most frequently collected species from IAI (28.3%),
      followed by Klebsiella spp. (20.8%), Enterococcus spp. (11.8%), and
      Stenotrophomonas maltophilia (6.3%). Isolates collected from IAI had the
      following tigecycline MIC(90) values: E. coli (1 MUg/mL), Klebsiella spp. and
      other Enterobacteriaceae (2 MUg/mL), Enterococcus spp. (0.25 MUg/mL), and S.
      maltophilia (1 MUg/mL). Tigecycline in vitro activity was observed against a
      broad spectrum of bacterial species, including strains resistant to other
      antimicrobial classes.

PMID- 24582581
TI  - Prompt detection of influenza A and B viruses using the BD VeritorTM System Flu
      A+B, Quidel(r) Sofia(r) Influenza A+B FIA, and Alere BinaxNOW(r) Influenza A&B
      compared to real-time reverse transcription-polymerase chain reaction (RT-PCR).
AB  - The performance characteristics of rapid influenza diagnostic tests vary widely.
      This study evaluated the BD VeritorTM System Flu A+B (Veritor; BD Diagnostics,
      Sparks, MD, USA), Quidel(r) Sofia(r) Influenza A+B FIA (Sofia; Quidel Corp., San
      Diego, CA, USA), and Alere BinaxNOW(r) Influenza A&B (Binax; Alere Scarborough,
      Inc., Scarborough, ME, USA) compared to reverse transcription-polymerase chain
      reaction (RT-PCR) for detection of influenza viruses in nasal wash specimens from
      240 pediatric patients. Positive percent agreements for influenza A and B virus
      detection were 93.8% and 94.2%, 95.8% and 98.1%, and 79.2% and 80.8% for Veritor,
      Sofia, and Binax, respectively. The Veritor and Binax tests demonstrated negative
      percent agreements >97.9% for detection of both influenza viruses, but the
      negative percent agreement of the Sofia test was 91.1% for influenza A and 70.7%
      for influenza B virus. Overall, the Veritor and Sofia tests were nearly as
      sensitive as RT-PCR and considerably more sensitive than Binax for detection of
      influenza viruses. However, the accuracy of the Sofia test was significantly
      lower than either Veritor or Binax. 

PMID- 24582582
TI  - Prior colonization is associated with increased risk of antibiotic-resistant Gram
      negative bacteremia in cancer patients.
AB  - We hypothesized that prior colonization with antibiotic-resistant Gram-negative
      bacteria is associated with increased risk of subsequent antibiotic-resistant
      Gram-negative bacteremia among cancer patients. We performed a matched case
      control study. Cases were cancer patients with a blood culture positive for
      antibiotic-resistant Gram-negative bacteria. Controls were cancer patients with a
      blood culture not positive for antibiotic-resistant Gram-negative bacteria. Prior
      colonization was defined as any antibiotic-resistant Gram-negative bacteria in
      surveillance or non-sterile-site cultures obtained 2-365 days before the
      bacteremia. Thirty-two (37%) of 86 cases and 27 (8%) of 323 matched controls were
      previously colonized by any antibiotic-resistant Gram-negative bacteria. Prior
      colonization was strongly associated with antibiotic-resistant Gram-negative
      bacteremia (odds ratio [OR] 7.2, 95% confidence interval [CI] 3.5-14.7) after
      controlling for recent treatment with piperacillin-tazobactam (OR 2.5, 95% CI 1.3
      4.8). In these patients with suspected bacteremia, prior cultures may predict
      increased risk of antibiotic-resistant Gram-negative bacteremia. 

PMID- 24582583
TI  - Evaluation of the AdvanSureTM real-time RT-PCR compared with culture and Seeplex
      RV15 for simultaneous detection of respiratory viruses.
AB  - Recently, AdvanSureTM kit based on multiplex real-time PCR was developed for
      simultaneous detection of 14 respiratory viruses (RVs). We compared the
      performance of AdvanSure with those of Seeplex(r) RV 15 ACE and culture by
      determining their sensitivities and specificities against a composite reference
      standard. Four hundred thirty-seven respiratory samples were tested by modified
      shell vial culture method, RV 15 ACE, and AdvanSure. One hundred fourteen samples
      (26.2%) out of 437 samples were positive by culture, while additional 91 (20.8%)
      were positive by AdvanSure or RV15. One hundred twelve of 114 culture-positive
      samples were positive by AdvanSure except 2 samples (1 adenovirus, 1 respiratory
      syncytial virus [RSV]). Overall, the sensitivities of culture, RV15, and
      AdvanSure were 74.5%, 89.8%, and 95.1%, respectively. Sensitivities of culture,
      RV15, and AdvanSure for each virus tested were as follows: 91/100/96% for
      influenza A, 60/0/100% for influenza B, 63/95/97% for RSV, 69/81/89% for
      adenovirus, and 87/93/93% for parainfluenza virus. For viruses not covered by
      culture, sensitivities of RV15 and AdvanSure were as follows: 77/88% for
      rhinovirus, 100/100% for coronavirus OC43, 40/100% for coronavirus 229E/NL63,
      13/100% for metapneumovirus, and 44/100% for bocavirus. The overall specificities
      of culture, RV15, and AdvanSure were 100/98.9/99.5%, respectively. Of 45
      coinfected specimens, AdvanSure detected 41 specimens (91.1%) as coinfected,
      while RV15 detected 27 specimens (60.0%) as coinfected. AdvanSure assay
      demonstrated exquisite performance for the detection of RVs and will be a
      valuable tool for the management of RV infection. 

PMID- 24582584
TI  - Stimulus collative properties and consumers' flavor preferences.
AB  - The present work investigated consumers' hedonic response to flavor stimuli in
      light of Berlyne's collative-motivational model of aesthetic preferences.
      According to this paradigm, sensory preferences are a function of a stimulus'
      arousal potential, which is determined by its collative properties. The
      relationship between overall arousal potential and hedonic response takes the
      shape of an inverted "U", reaching an optimum at a certain level of arousal
      potential. In three independent studies, using different sets of novel beers as
      stimuli, consumers reported their hedonic response and rated three collative
      properties: novelty, familiarity and complexity. Relationships between these
      collative properties and hedonic ratings were explored by polynomial regression.
      The results revealed patterns in line with Berlyne's predictions (curvilinear
      relationship) with regard to perceived novelty, whereas mixed results were
      obtained for familiarity and complexity. Additionally, in two of the studies, the
      moderating role of relevant consumer characteristics - product knowledge, food
      neophobia and variety seeking tendency - was investigated. A consumer's degree of
      product knowledge was found to significantly reduce perceived complexity and
      novelty, ostensibly reflecting the learning that occurs with previous exposures. 

PMID- 24582585
TI  - Maltodextrin can produce similar metabolic and cognitive effects to those of
      sucrose in the rat.
AB  - In the context of the well-documented metabolic and behavioural effects of
      supplementing rats' diets with access to a sucrose solution, the aim of this
      study was to compare the impact of 10% sucrose with that of an isoenergetic
      (10.4%) solution of hydrolysed starch, maltodextrin. This polysaccharide is
      metabolised at least as rapidly as sucrose and is also very palatable to rats,
      but does not contain fructose. Each of three experiments contained three groups:
      one given a sucrose solution, one given a maltodextrin solution and a control
      group maintained on standard chow and water alone. In Experiment 1 the sucrose
      and maltodextrin groups were given their supplementary drinks for 2 h each day,
      while in Experiments 2 and 3 these groups had 24-h access to their supplements.
      Ad libitum access to maltodextrin produced at least as rapid weight gain as
      sucrose and in Experiment 2 retroperitoneal fat mass was greater in the two
      carbohydrate groups than in the control group. Moreover, in Experiment 3,
      impaired performance on a location recognition task was also found in both
      carbohydrate groups after only 17 days on the diets. These results indicate that
      the harmful effects of excess sucrose consumption can also be produced by another
      rapidly absorbed carbohydrate that does not contain fructose. 

PMID- 24582586
TI  - Dissection of superior mesenteric artery associated with Behcet's disease.

PMID- 24582587
TI  - Annexins - scaffolds modulating PKC localization and signaling.
AB  - Spatial and temporal organization of signal transduction is critical to link
      different extracellular stimuli with distinct cellular responses. A classical
      example of hormones and growth factors creating functional diversity is
      illustrated by the multiple signaling pathways activated by the protein kinase C
      (PKC) family of serine/threonine protein kinases. The molecular requirements for
      diacylglycerol (DAG) and calcium (Ca(2+)) to promote PKC membrane translocation,
      the hallmark of PKC activation, have been clarified. However, the underlying
      mechanisms that establish selectivity of individual PKC family members to
      facilitate differential substrate phosphorylation and varied signal output are
      still not fully understood. It is now well believed that the coordinated control
      and functional diversity of PKC signaling involves the formation of PKC isozyme
      specific protein complexes in certain subcellular sites. In particular,
      interaction of PKC isozymes with compartment and signal-organizing scaffolds,
      including receptors for activated C-kinase (RACKs), A-kinase-anchoring proteins
      (AKAPs), 14-3-3, heat shock proteins (HSP), and importins target PKC isozymes to
      specific cellular locations, thereby delivering PKC isozymes into close proximity
      of their substrates. In addition, several annexins (Anx), including AnxA1, A2, A5
      and A6, display specific and distinct abilities to interact and promote membrane
      targeting of different PKC isozymes. Together with the ability of annexins to
      create specific membrane microenvironments, this is likely to enable PKCs to
      phosphorylate certain substrates and regulate their downstream effector pathways
      in specific cellular sites. This review aims to summarize the capacity of
      annexins to modulate the localization and activity of PKC family members and
      participate in the spatiotemporal regulation of PKC signaling in health and
      disease. 

PMID- 24582588
TI  - Insulin activation of vacuolar protein sorting 34 mediates localized
      phosphatidylinositol 3-phosphate production at lamellipodia and activation of
      mTOR/S6K1.
AB  - The class III phosphatidylinositol 3-kinase, VPS34, phosphorylates the D3
      hydroxyl of inositol generating phosphatidylinositol 3-phosphate (ptdins(3)p).
      Initial studies suggested that ptdins(3)p solely functioned as a component of
      vesicular and endosomal membranes and that VPS34 did not function in signal
      transduction. However, VPS34 has recently been shown to be required for insulin
      mediated activation of S6 kinase 1 (S6K1). Whether VPS34 activity is directly
      regulated by insulin is unclear. It is also not known whether VPS34 activity can
      be spatially restricted in response to extracellular stimuli. Data presented here
      demonstrate that in response to insulin, VPS34 is activated and translocated to
      lamellipodia where it produces ptdins(3)p. The localized production of ptdins(3)p
      is dependent on Src phosphorylation of VPS34. In cells expressing VPS34 with
      mutations at Y231 or Y310, which are Src-phosphorylation sites, insulin
      stimulated VPS34 translocation to the plasma membrane and lamellipodia formation
      are blocked. mTOR also colocalizes with VPS34 and ptdins(3)p at lamellipodia
      following insulin-stimulation. In cells expressing the VPS34-Y231F mutant, which
      blocks lamellipodia formation, mTOR localization at the plasma membrane and
      insulin-mediated S6K1 activation are reduced. This suggests that mTOR
      localization at lamellipodia is important for full activation of S6K1 induced by
      insulin. These data demonstrate that insulin can spatially regulate VPS34
      activity through Src-mediated tyrosine phosphorylation and that this membrane
      localized activity contributes to lamellipodia formation and activation of
      mTOR/S6K1signaling.

PMID- 24582589
TI  - Overexpression of atypical protein kinase C in HeLa cells facilitates
      macropinocytosis via Src activation.
AB  - Atypical protein kinase C (aPKC) is the first recognized kinase oncogene.
      However, the specific contribution of aPKC to cancer progression is unclear. The
      pseudosubstrate domain of aPKC is different from the other PKC family members,
      and therefore a synthetic peptide corresponding to the aPKC pseudosubstrate (aPKC
      PS) sequence, which specifically blocks aPKC kinase activity, is a valuable tool
      to assess the role of aPKC in various cellular processes. Here, we learned that
      HeLa cells incubated with membrane permeable aPKC-PS peptide displayed dilated
      heterogeneous vesicles labeled with peptide that were subsequently identified as
      macropinosomes. A quantitative membrane binding assay revealed that aPKC-PS
      peptide stimulated aPKC recruitment to membranes and activated Src. Similarly,
      aPKC overexpression in transfected HeLa cells activated Src and induced
      macropinosome formation. Src-aPKC interaction was essential; substitution of the
      proline residues in aPKC that associate with the Src-SH3 binding domain rendered
      the mutant kinase unable to induce macropinocytosis in transfected cells. We
      propose that aPKC overexpression is a contributing factor to cell transformation
      by interacting with and consequently promoting Src activation and constitutive
      macropinocytosis, which increases uptake of extracellular factors, required for
      altered cell growth and accelerated cell migration. 

PMID- 24582590
TI  - Lack of association of IRF5 gene polymorphisms with autoimmune thyroid disease: a
      case-control study. IRF5 gene and AITD.
AB  - BACKGROUND: Several studies support a link between autoimmunity and interferon
      regulatory factor 5 (IRF5) gene polymorphisms. We have taken the opportunity to
      examine association of the autoimmune disease risk gene, the interferon
      regulatory factor 5 (IRF5) to survey its susceptibility to autoimmune thyroid
      disease. "A total of 667 patients with autoimmune thyroid diseases and 301
      healthy controls were genotyped for rs10954213, rs2004640, rs3807306, rs752637
      and rs7808907 of IRF5 gene polymorphisms". We further investigated the
      association between BANK1 gene and IRF5 gene in AITD patients. RESULTS: For IRF5
      gene, both in allele and genotype frequencies from both GD and HT patients were
      not significantly different from those of controls. Association between
      rs7808907C allele and Graves' disease showed trend towards significance
      (P=0.067). Haplotype results in IRF5 represented in the same block, without
      significant association. No significant association was found between all IRF5
      SNPs and ophthalmopathy in Graves' patients. Additive interaction analysis
      revealed no interactions between IRF5 and BANK1 gene in AITD patients.
      CONCLUSION: Our data fail to reveal IRF5 as a susceptibility gene to AITD and do
      not support additive effect of IRF5 to BANK1 gene.

PMID- 24582591
TI  - Assessment of serum apelin and lipocalin-2 levels in patients with subclinical
      hypothyroidism.
AB  - OBJECTIVES: Subclinical hypothyroidism is the precursor to hypothyroidism because
      it has a tendency to transform into hypothyroidism. Subclinical hypothyroidism is
      considered one of the risk factors causing metabolic syndrome. Metabolic syndrome
      can be characterized by plasma levels of apelin and lipocalin-2, both released
      from adipocytes. In the present study, we aimed to measure serum apelin and
      lipocalin-2 levels of patients with subclinical hypothyroidism and compare them
      with serum apelin and lipocalin-2 levels from healthy individuals. METHODS: This
      was a cross-sectional study. A total of 80 subjects were enrolled in the study
      and divided into two groups: Group A included 39 patients (females, n=34)
      diagnosed with subclinical hypothyroidism, and Group B (the control group)
      comprised 41 healthy volunteers (females, n=38). Serum samples were obtained from
      each participant for the measurement of apelin and lipocalin-2. These were then
      stored at minus 80 degrees C until the time of analysis, when serum apelin and
      lipocalin-2 levels of the two groups were compared. RESULTS: Patients with
      subclinical hypothyroidism (Group A and Group B subjects [healthy controls]) were
      comparable with respect to gender, age, and body mass index (BMI) (P=0.412,
      P=0.863, and P=0.269, respectively), nor was there a statistically significant
      difference between groups in terms of apelin and lipocalin-2 levels (P=0.87, and
      P=0.67, respectively). Apelin levels showed a positive and significant
      correlation with BMI (P=0.034). Serum lipocalin-2 levels showed significant
      positive correlations with BMI and creatinine levels (P=0.002, and P=0.025,
      respectively). CONCLUSION: In the present study, no significant difference of
      serum apelin and lipocalin-2 levels was observed between patients with
      subclinical hypothyroidism and healthy control subjects. Positive correlations
      were found, however, between serum apelin level and BMI as well as between serum
      lipocalin-2 and BMI and creatinine levels.

PMID- 24582592
TI  - Anxiolytic-like effect of danshensu [(3-(3,4-dihydroxyphenyl)-lactic acid)] in
      mice.
AB  - AIMS: Danshensu [3-(3,4-dihydroxyphenyl)-lactic acid], a phenylpropanoid compound
      isolated from Prunella vulgaris var. lilacina, is a well-known antioxidant.
      Although its antioxidant activity and cardioprotective effect have been reported,
      the pharmacological properties of danshensu in the central nervous system remain
      unclear. We investigated whether danshensu exerts anxiolytic-like activity in
      mice. MAIN METHODS: We conducted monoamine oxidase A (MAO-A) inhibition assay on
      danshensu in vitro, and behavioral tests including the elevated plus-maze test
      (EPM), the hole-board test, the rotarod test and the open field test were
      employed. KEY FINDINGS: We found that danshensu significantly inhibited the
      activity of MAO-A in vitro. The administration of danshensu (3 or 10mg/kg)
      produced a significant anxiolytic-like effect in the EPM and hole-board test. In
      addition, no changes in the spontaneous locomotor activity and no myorelaxant
      effects were observed compared to the control group; these effects were confirmed
      with the open field test and the rotarod test. Moreover, the anxiolytic-like
      properties of danshensu were antagonized by a dopamine D1 receptor antagonist
      (SCH 23390) but not by a 5-HT1A receptor antagonist (WAY 100635) or an alpha1
      adrenergic receptor antagonist (prazosin). SIGNIFICANCE: These results indicate
      that danshensu exerts its anxiolytic-like properties, in part, through
      dopaminergic neurotransmitter signaling.

PMID- 24582593
TI  - The role of mTOR in depression and antidepressant responses.
AB  - The aim of this study was to characterize the mTOR signaling cascade in
      depression and the actions that antidepressant drugs have on this pathway.
      Herein, a literature review was performed by verification and comparison of
      textbooks and journal articles that describe the characterization of the mTOR
      signaling cascade and its relationship to depression and antidepressant drugs,
      especially ketamine. Postmortem studies have shown robust deficits in the
      mammalian target of rapamycin (mTOR) signaling in the prefrontal cortex of
      subjects diagnosed with major depressive disorder. However, besides the mTOR
      signaling pathway having an antidepressant response to various drugs, this seems
      to be more associated with antidepressant N-methyl-d-aspartate (NMDA) receptor
      antagonists, such as ketamine. The characterization of the mTOR signaling pathway
      in depression and its action in response to antidepressants show great potential
      for the identification of new therapeutic targets for the development of
      antidepressant drugs. 

PMID- 24582594
TI  - Apigenin isolated from Daphne genkwa Siebold et Zucc. inhibits 3T3-L1
      preadipocyte differentiation through a modulation of mitotic clonal expansion.
AB  - AIMS: Obesity develops when energy intake chronically exceeds total energy
      expenditure. We sought to assess whether the flavonoid-rich fraction of crude
      extracts from Daphne genkwa Siebold et Zuccarini (GFF) might inhibit adipogenesis
      of 3T3-L1 cells. MAIN METHODS: Cell viability of 3T3-L1 preadipocytes was
      assessed by MTT assays, and lipid accumulation was measured by Oil Red O.
      Adipogenesis related factors were checked by Western blot analysis. Flow
      cytometry was used to analyze the mitotic cell cycle during the mitotic clonal
      expansion phase. KEY FINDINGS: Among five flavonoids isolated from GFF, only
      apigenin potently inhibited the differentiation of 3T3-L1 cells. Apigenin reduced
      CCAAT/enhancer binding protein (C/EBP) alpha and peroxisome proliferator
      activated receptor gamma levels. Apigenin-treated 3T3-L1 cells failed to undergo
      clonal expansion during the early phase of adipocyte differentiation. Apigenin
      arrested cell cycle progression at the G0/G1 phase. This effect was associated
      with a marked decrease in cyclin D1 and cyclin-dependent kinase 4 expression,
      with the concomitant and sustained expression of p27(Kip1). In addition, apigenin
      inhibited the DNA-binding activity of C/EBPbeta in differentiating 3T3-L1 cells
      by down-regulating the 35kDa isoform of C/EBPbeta (liver-enriched activating
      protein) and up-regulating the expression of two different sets of C/EBP
      inhibitors: C/EBP homologous protein and the phospho-liver-enriched inhibitory
      protein isoform of C/EBPbeta. SIGNIFICANCE: These findings suggest that apigenin
      can prevent 3T3-L1 preadipocyte differentiation by the inhibition of the mitotic
      clonal expansion and the adipogenesis related factors and upregulation of the
      expression of multiple C/EBPbeta inhibitors.

PMID- 24582595
TI  - Influence of sulphate on the composition and antibacterial and antiviral
      properties of the exopolysaccharide from Porphyridium cruentum.
AB  - AIMS: The influence of two culture media and three different concentrations of
      sulphate in the medium on the growth of two strains of Porphyridium cruentum and
      on the production, composition and viscoelastic characteristics, and
      antimicrobial properties of the sulphated exopolysaccharide (EPS) were studied.
      MAIN METHODS: A Bohlin C50 rheometer was used to evaluate the viscosity and
      elasticity of the EPS solutions. HSV virus, types 1 and 2, Vaccinia virus and
      Vesicular stomatitis virus were used along with two Gram-negative (Escherichia
      coli and Salmonella enteritidis) and one Gram-positive (Staphylococcus aureus)
      bacteria, for testing the antimicrobial activity of EPS. KEY-FINDINGS: The growth
      of microalgae was higher in NTIP medium and the production of EPS was enhanced by
      sulphate 21mM. The protein content of the EPS was enhanced by the addition of
      sulphate 52mM and 104mM; this concentration also induced an increase in sulphate
      content of the EPS. However, neither the contents of EPS in carbohydrates and
      uronic acids were affected by the culture medium supplementation in sulphate. In
      general, the EPS from the Spanish strain presented a higher antiviral activity
      than the EPS from the Israeli strain. All EPS extracts revealed a strong activity
      against V. stomatitis virus, higher than the activity of all chemical compounds
      tested. The EPS from the Israeli strain also presented antibacterial activity
      against S. enteritidis. SIGNIFICANCE: Enrichment of the culture medium with
      sulphate improved protein and sulphate content of EPS. EPS extracts presented a
      relevant activity against V. stomatitis virus and S. enteritidis bacterium.

PMID- 24582597
TI  - Face processing in depersonalization: an fMRI study of the unfamiliar self.
AB  - Depersonalization disorder (DPD) is characterized by a core sense of
      unfamiliarity. Nine DPD participants and 10 healthy controls underwent functional
      magnetic resonance imaging while viewing self and unfamiliar faces. Compared with
      control subjects, the DPD group exhibited significantly greater activation in
      several brain regions in response to self vs. stranger faces. Implications are
      discussed. 

PMID- 24582596
TI  - Effect of resveratrol on mitochondrial function: implications in parkin
      associated familiar Parkinson's disease.
AB  - Mitochondrial dysfunction and oxidative stress occur in Parkinson's disease (PD),
      but the molecular mechanisms controlling these events are not completely
      understood. Peroxisome proliferator-activated receptor-gamma coactivator-1alpha
      (PGC-1alpha) is a transcriptional coactivator known as master regulator of
      mitochondrial functions and oxidative metabolism. Recent studies, including one
      from our group, have highlighted altered PGC-1alpha activity and transcriptional
      deregulation of its target genes in PD pathogenesis suggesting it as a new
      potential therapeutic target. Resveratrol, a natural polyphenolic compound proved
      to improve mitochondrial activity through the activation of several metabolic
      sensors resulting in PGC-1alpha activation. Here we have tested in vitro the
      effect of resveratrol treatment on primary fibroblast cultures from two patients
      with early-onset PD linked to different Park2 mutations. We show that resveratrol
      regulates energy homeostasis through activation of AMP-activated protein kinase
      (AMPK) and sirtuin 1 (SIRT1) and raise of mRNA expression of a number of PGC
      1alpha's target genes resulting in enhanced mitochondrial oxidative function,
      likely related to a decrease of oxidative stress and to an increase of
      mitochondrial biogenesis. The functional impact of resveratrol treatment
      encompassed an increase of complex I and citrate synthase activities, basal
      oxygen consumption, and mitochondrial ATP production and a decrease in lactate
      content, thus supporting a switch from glycolytic to oxidative metabolism.
      Moreover, resveratrol treatment caused an enhanced macro-autophagic flux through
      activation of an LC3-independent pathway. Our results, obtained in early-onset PD
      fibroblasts, suggest that resveratrol may have potential clinical application in
      selected cases of PD-affected patients. 

PMID- 24582599
TI  - Drug discovery through stem cell-based organoid models.
AB  - The development of new drugs is currently a long and costly process in large part
      due to the failure of promising drug candidates identified in initial in vitro
      screens to perform as intended in vivo. New approaches to drug screening are
      being developed which focus on providing more biomimetic platforms. This review
      surveys this new generation of drug screening technologies, and provides an
      overview of recent developments in organoid culture systems which could afford
      previously unmatched fidelity for testing bioactivity and toxicity. The
      challenges inherent in such approaches will also be discussed, with a view
      towards bridging the gap between proof-of-concept studies and a wider
      implementation within the drug development community. 

PMID- 24582598
TI  - Site-specific insertion of selenium into the redox-active disulfide of the
      flavoprotein augmenter of liver regeneration.
AB  - Augmenter of liver regeneration (sfALR) is a small disulfide-bridged homodimeric
      flavoprotein with sulfhydryl oxidase activity. Here, we investigate the catalytic
      and spectroscopic consequences of selectively replacing C145 by a selenocysteine
      to complement earlier studies in which random substitution of ~90% of the 6
      cysteine residues per sfALR monomer was achieved growing Escherichia coli on
      selenite. A selenocysteine insertion sequence (SECIS) element was installed
      within the gene for human sfALR. SecALR2 showed a spectrum comparable to that of
      wild-type sfALR. The catalytic efficiency of SecALR2 towards dithiothreitol was
      6.8-fold lower than a corresponding construct in which position 145 was returned
      to a cysteine residue while retaining the additional mutations introduced with
      the SECIS element. This all-cysteine control enzyme formed a mixed disulfide
      between C142 and beta-mercaptoethanol releasing C145 to form a thiolate-flavin
      charge transfer absorbance band at ~530nm. In contrast, SecALR2 showed a
      prominent long-wavelength absorbance at 585 nm consistent with the expectation
      that a selenolate would be a better charge-transfer donor to the isoalloxazine
      ring. These data show the robustness of the ALR protein fold towards the multiple
      mutations required to insert the SECIS element and provide the first example of a
      selenolate to flavin charge-transfer complex.

PMID- 24582600
TI  - Oxygen supply to encapsulated therapeutic cells.
AB  - Therapeutic cells encapsulated in immunobarrier devices have promise for
      treatment of a variety of human diseases without immunosuppression. The absence
      of sufficient oxygen supply to maintain viability and function of encapsulated
      tissue has been the most critical impediment to progress. Within the framework of
      oxygen supply limitations, we review the major issues related to development of
      these devices, primarily in the context of encapsulated islets of Langerhans for
      treating diabetes, including device designs and materials, supply of tissue,
      protection from immune rejection, and maintenance of cell viability and function.
      We describe various defensive measures investigated to enhance survival of
      transplanted tissue, and we review the diverse approaches to enhancement of
      oxygen transport to encapsulated tissue, including manipulation of diffusion
      distances and oxygen permeability of materials, induction of neovascularization
      with angiogenic factors and vascularizing membranes, and methods for increasing
      the oxygen concentration adjacent to encapsulated tissue so as to exceed that in
      the microvasculature. Recent developments, particularly in this latter area,
      suggest that the field is ready for clinical trials of encapsulated therapeutic
      cells to treat diabetes. 

PMID- 24582601
TI  - Accumulation of persistent organic pollutants in parasites.
AB  - Organisms are simultaneously exposed to various stressors, including parasites
      and pollutants, that may interact with each other. Research on the accumulation
      of organic compounds in host-parasite systems is scant compared to studies on
      parasite-metal interactions and mainly focuses on intestinal endoparasites. We
      reviewed factors that determine the accumulation of persistent organic pollutants
      (POPs) in host-parasite systems. The wet/dry weight-based concentration of POPs
      in these parasites is usually lower than that in host tissues because of lower
      lipid contents in the parasites. However, the fractionation of the pollutants
      into parasites and their hosts may vary, depending on developmental stages in the
      life cycle of the parasites. Developmental stages determine the trophic
      relationship and the taxon of the parasite in the host-parasite systems because
      of different feeding strategies between the stages. Lipid-corrected
      concentrations of organic chemicals in the host are usually higher than those in
      the endoparasites studied. This phenomenon is attributed to a number of
      physiological and behavioural processes, such as feeding selectivity and strategy
      and excretion. Moreover, no significant relationship was found between the
      accumulation factor (i.e. the ratio between the lipid-corrected concentrations in
      parasites and in their hosts) for polychlorinated biphenyls and either
      hydrophobicity or molecular size. At the intermediate hydrophobicity, larger and
      more lipophilic compounds are accumulated at higher levels in both parasites and
      the host than smaller and less lipophilic compounds. The bioaccumulation of POPs
      in parasites is affected by some other abiotic, e.g. temperature, and biotic
      factors, e.g. the number of host species infected by parasites. 

PMID- 24582602
TI  - Application of biochar from sewage sludge to plant cultivation: Influence of
      pyrolysis temperature and biochar-to-soil ratio on yield and heavy metal
      accumulation.
AB  - Applying biochar products from sewage sludge (SS) pyrolysis as soil amendment for
      plant cultivation was investigated in this study with special attention paid to
      heavy metal accumulation in the plants when pyrolysis temperature and biochar-to
      soil mass ratio (C:S) were changed. Biochar obtained at four different
      temperatures were adopted as soil amendment for Allium sativum L. garlic plant
      cultivation. Experimental results revealed that biochars were rich in nutrient
      contents and they improved garlic yields. Although contents of heavy metals
      including As, Zn, Pb, Ni, Cd, Cr and Cu, etc. were elevated in the biochars
      compared to local soil, they fell within the acceptable limits for land
      application and SS is a suitable biochar resource, especially biochar produced at
      450 degrees C had rich micropores, relatively stable functional groups in
      structure and rugged surface to contact well with soil, conducive to its usage as
      a biochar. The garlic grew faster when planted in the biochar-amended soil and
      had higher final dry matter yields than those planted in the reference soil,
      especially biochar produced at 450 degrees C corresponding to the highest final
      yields. The C:S ratio related to the highest garlic yields changed when the
      pyrolysis temperature was changed and this ratio was 1:4 for the biochar produced
      at 450 degrees C. General heavy metal accumulation in the garlic occurred only
      for the most enriched Zn and Cu, and mainly in the roots & bulbs; in addition
      this bioaccumulation was increasing as leaching from biochar increased but not
      increasing with C:S ratio. The garlic planted in soil amended with biochar of 450
      degrees C contained the lowest level of heavy metals compared to other biochars.
      Those results indicated that heavy metal accumulation in plants can be inhibited
      through proper pyrolysis temperature choice and prevention of heavy metal
      leaching from the SS biochar. 

PMID- 24582603
TI  - Ketamine and intraocular pressure in children.
AB  - STUDY OBJECTIVE: We determine the increase in intraocular pressure during
      pediatric procedural sedation with ketamine, and the proportion of children whose
      increase might be clinically important (at least 5 mm Hg). METHODS: We
      prospectively enrolled children aged 8 to 18 years, chosen to receive ketamine
      sedation in a pediatric emergency department. We measured intraocular pressure
      before sedation, immediately after ketamine administration, 2 minutes post-drug
      administration, and every 5 minutes thereafter until recovery or 30 minutes after
      the final dose. We descriptively report our observations. RESULTS: For the 60
      children enrolled, the median intraocular pressure increase was 3 mm Hg (range 0
      to 8 mm Hg). Fifteen children had a brief greater than or equal to 5 mm Hg
      increase in intraocular pressure from baseline. CONCLUSION: In this study of
      ketamine sedation in children with healthy eyes, we observed mild increases in
      intraocular pressure that at times transiently exceeded our bounds for potential
      clinical importance (5 mm Hg).

PMID- 24582604
TI  - Do glucocorticoids provide benefit to children with bronchiolitis?

PMID- 24582605
TI  - Setting wait times to achieve targeted left-without-being-seen rates.
AB  - BACKGROUND: Although several studies have demonstrated that wait time is a key
      factor that drives high leave-without-being-seen (LWBS) rates, limited data on
      ideal wait times and impact on LWBS rates exist. STUDY OBJECTIVES: We studied the
      LWBS rates by triage class and target wait times required to achieve various LWBS
      rates. METHODS: We conducted a 3-year retrospective analysis of patients
      presenting to an urban, tertiary, academic, adult emergency department (ED). We
      divided the 3-year study period into 504 discrete periods by year, day of the
      week, and hour of the day. Patients of same triage level arriving in the same bin
      were exposed to similar ED conditions. For each bin, we calculate the mean actual
      wait time and the proportion of patients that abandoned. We performed a
      regression analysis on the abandonment proportion on the mean wait time using
      weighted least squares regression. RESULTS: A total of 143,698 patients were
      included for analysis during the study period. The R(2) value was highest for
      Emergency Severity Index (ESI) 3 (R(2) = 0.88), suggesting that wait time is the
      major factor driving LWBS of ESI 3 patients. Assuming that ESI 2 patients wait
      less than 10 minutes, our sensitivity analysis shows that the target wait times
      for ESI 3 and ESI 4/5 patients should be less than 45 and 60 minutes,
      respectively, to achieve an overall LWBS rate of less than 2%. CONCLUSION:
      Achieving target LWBS rates requires analysis to understand the abandonment
      behavior and redesigning operations to achieve the target wait times.

PMID- 24582606
TI  - Late positive flecainide challenge test for Brugada syndrome.

PMID- 24582608
TI  - Development of cell-based bioassay with Sf9 cells expressing TcSKR1 and TcSKR2
      and differential activation by sulfated and non-sulfated SK peptides.
AB  - Insect sulfakinin receptors (SKRs) are G-protein-coupled receptors (GPCRs) that
      interact with sulfakinins (SKs) to modulate diverse biological processes. One of
      the indispensable roles of SKs is in the regulation of food intake in insects. In
      this project we report on the development of a cell-based receptor assay system
      with insect Sf9 cells, expressing TcSKR1 and TcSKR2 from the red flour beetle
      Tribolium castaneum, a model and important pest insect in agriculture. In this
      system, a stable presence of the two TcSKRs was supported by Western blotting.
      The expressed TcSKRs were coupled to Galphas-protein upon activation and
      stimulated cAMP accumulation in Sf9 cells. Exposure of the transfected cell lines
      to sulfated SK (sSK) activated TcSKR1 at 1 nM; the EC50 of sSK to obtain 50% of
      receptor activation was similar for both receptors. In contrast, MUM
      concentrations of non-sulfated SK were necessary to activate both TcSKRs. In
      conclusion, this cell-based TcSKR assay system is useful to screen SK-related
      peptides and mimetics and to better document ligand-receptor structure-activity
      relationships. Given the importance of SK signaling system in insects, the
      present study may provide new insights on the development of new methods to
      control pest insects.

PMID- 24582607
TI  - A truncating SCN5A mutation combined with genetic variability causes sick sinus
      syndrome and early atrial fibrillation.
AB  - BACKGROUND: Mutations in the SCN5A gene, encoding the alpha subunit of the
      cardiac Na(+) channel, Nav1.5, can result in several life-threatening
      arrhythmias. OBJECTIVE: To characterize a distal truncating SCN5A mutation,
      R1860Gfs*12, identified in a family with different phenotypes including sick
      sinus syndrome, atrial fibrillation (AF), atrial flutter, and atrioventricular
      block. METHODS: Patch-clamp and biochemical analyses were performed in human
      embryonic kidney 293 cells transfected with wild-type (WT) and/or mutant
      channels. RESULTS: The mutant channel expressed alone caused a 70% reduction in
      inward sodium current (INa) density compared to WT currents, which was consistent
      with its partial proteasomal degradation. It also led to a negative shift of
      steady-state inactivation and to a persistent current. When mimicking the
      heterozygous state of the patients by coexpressing WT and R1860Gfs*12 channels,
      the biophysical properties of INa were still altered and the mutant channel alpha
      subunits still interacted with the WT channels. Since the proband developed
      paroxysmal AF at a young age, we screened 17 polymorphisms associated with AF
      risk in this family and showed that the proband carries at-risk polymorphisms
      upstream of PITX2, a gene widely associated with AF development. In addition,
      when mimicking the difference in resting membrane potentials between cardiac
      atria and ventricles in human embryonic kidney 293 cells or when using computer
      model simulations, R1860Gfs*12 induced a more drastic decrease in INa at the
      atrial potential. CONCLUSION: We have identified a distal truncated SCN5A mutant
      associated with gain- and loss-of-function effects, leading to sick sinus
      syndrome and atrial arrhythmias. A constitutively higher susceptibility to
      arrhythmias of atrial tissues and genetic variability could explain the complex
      phenotype observed in this family.

PMID- 24582609
TI  - Solubilization and reconstitution of the mu-opioid receptor expressed in human
      neuronal SH-SY5Y and CHO cells.
AB  - The zwitterionic detergent CHAPS was used to solubilize the human mu-opioid
      receptor (hMOR) from SH-SY5Y neuroblastoma cells and recombinant hMOR-CHO (CHO-T7
      hMOR) and hMOR-SH-SY5Y (SH-SY5Y-T7-hMOR) cell membranes. Agonist stimulation and
      G-protein activation by the mu-selective opioid agonist DAMGO ([D-Ala2, N-MePhe4,
      Gly-ol]-enkephalin) were recovered after removing of CHAPS after polyethylene
      glycol (PEG) precipitation. Binding assays show that hMOR solubilized and
      reconstituted this way was functional and able to interact with both agonist
      peptides and with G-protein. The effective solubilization and reconstitution of
      hMOR from mammalian cells, without truncation and extensive modification,
      represent an essential step toward the purification of a receptor bearing
      important post-translational modifications. 

PMID- 24582610
TI  - Management of coexistent intracranial aneurysms and extracranial carotid
      atherosclerotic disease.

PMID- 24582611
TI  - Intracranial pressure measured in freely moving rats for days after intracerebral
      hemorrhage.
AB  - In some patients, intracerebral hemorrhage (ICH) causes life-threatening
      elevations in intracranial pressure (ICP) arising from mass effect of the
      hematoma and edema. Accordingly, edema is a common endpoint to gauge treatment
      efficacy in rodent ICH models. Despite widespread reliance on edema, its
      relationship with ICP and cerebral perfusion pressure (CPP) is unknown. Blood
      pressure (BP) and ICP were measured by telemetry devices in rats after
      collagenase ("severe" - 0.3U, and "moderate" - 0.15U doses) or blood infusion
      (100MUL) into striatum (vs. saline infused shams). We compared epidural and
      intraparenchymal ICP readings (collagenase), evaluated CPP (collagenase), and
      compared models. Moderate (9.46mmHg+/-4.72 SD, 3day average) and severe
      collagenase ICHs (10.79+/-3.50) significantly increased ICP versus shams (4.02+/
      2.09), whereas blood infusion did not (5.37+/-0.55). The two monitoring locations
      gave similar readings after severe collagenase ICH. Increased ICP reduced CPP by
      ~7.5mmHg for days after the larger collagenase infusion. CPP averaged from 103
      112mmHg in shams. Edema occurred in all ICH models and predicted ICP. However,
      ICP and CPP were only modestly changed even after severe ICH and edema. Thus,
      small changes in edema typically reported in the literature, which often use
      smaller bleeds than presently used, likely minimally affects ICP and CPP. Further
      research into the face validity of these models, endpoints, and their ability to
      evaluate therapeutics is needed. 

PMID- 24582612
TI  - Amino-acid mutations to extend the biological half-life of a therapeutically
      valuable mutant of human butyrylcholinesterase.
AB  - Cocaine is a widely abused and addictive drug without an FDA-approved medication.
      Our recently designed and discovered cocaine hydrolase, particularly E12-7
      engineered from human butyrylcholinesterase (BChE), has the promise of becoming a
      valuable cocaine abuse treatment. An ideal anti-cocaine therapeutic enzyme should
      have not only a high catalytic efficiency against cocaine, but also a
      sufficiently long biological half-life. However, recombinant human BChE and the
      known BChE mutants have a much shorter biological half-life compared to the
      native human BChE. The present study aimed to extend the biological half-life of
      the cocaine hydrolase without changing its high catalytic activity against
      cocaine. Our strategy was to design possible amino-acid mutations that can
      introduce cross-subunit disulfide bond(s) and, thus, change the distribution of
      the oligomeric forms and extend the biological half-life. Three new BChE mutants
      (E364-532, E377-516, and E535) were predicted to have a more stable dimer
      structure with the desirable cross-subunit disulfide bond(s) and, therefore, a
      different distribution of the oligomeric forms and a prolonged biological half
      life. The rational design was followed by experimental tests in vitro and in
      vivo, confirming that the rationally designed new BChE mutants, i.e. E364-532,
      E377-516, and E535, indeed had a remarkably different distribution of the
      oligomeric forms and prolonged biological half-life in rats from ~7 to ~13h
      without significantly changing the catalytic activity against (-)-cocaine. This
      is the first demonstration that rationally designed amino-acid mutations can
      significantly prolong the biological half-life of a high-activity enzyme without
      significantly changing the catalytic activity. 

PMID- 24582613
TI  - Modulation of HCN channels in lateral septum by nicotine.
AB  - The effects of addictive drugs most commonly occur via interactions with target
      receptors. The same is true of nicotine and its multiple receptors in a variety
      of cell types. However, there are also side effects for given substances that can
      dramatically change cellular, tissue, organ, and organism functions. In this
      study, we present evidence that nicotine possesses such properties, and modulates
      neuronal excitability. We recorded whole-cell voltages and currents in neurons
      situated in the dorsal portion of the lateral septum in acute coronal brain
      slices of adult rats. Our experiments in the lateral septum revealed that
      nicotine directly affects HCN - hyperpolarization-activated cyclic nucleotide
      gated non-selective cation channels. We demonstrate that nicotine effects persist
      despite the concurrent application of nicotinic acetylcholine receptors'
      antagonists - mecamylamine, methyllycaconitine, and dihydro-beta-erythroidine.
      These results are novel in regard to HCN channels in the septum, in general, and
      in their sensitivity to nicotine, in particular. 

PMID- 24582614
TI  - Novel co-axial prilling technique for the development of core-shell particles as
      delayed drug delivery systems.
AB  - In this study, biocompatible double layered beads consisting of pectin core and
      alginate shell were prepared through a single step manufacturing process based on
      prilling apparatus equipped with co-axial nozzles. The core was loaded with
      piroxicam (PRX) as model non-steroidal anti-inflammatory drug (NSAID).
      Morphology, size distribution and shape of the double layered beads varied
      depending on the operative conditions and polymer concentrations. Co-axial
      nozzles size, applied vibration frequency, gelling conditions and, mainly,
      polymers mass ratio were identified as critical variables. Particularly, the
      relative viscosity of polymeric feed solutions inside the nozzle was the key
      parameter to obtain homogeneous and well-formed coated particles. The produced
      beads were investigated for the release kinetic in different media. Once PRX was
      encapsulated within the pectin core, a controlled release pattern was observed.
      Particularly, beads produced with 4:1 core/shell ratio (F4) released less than
      30% of PRX in simulated gastric fluid (SGF) while total liberation of the drug
      was achieved during the next 3h in simulated intestinal fluid (SIF). More
      interesting, F4 tested in SIF was able to release drug in a delayed and sustained
      manner at established time points (2h_8.2%, 3h_32.2%, 4h_70.1% and 5h_about
      100%). Based on the above results, co-axial prilling approach is expected to
      provide success in manufacturing systems with delayed drug release profiles. Such
      systems may be potentially useful in targeting diseases which are affected by the
      circadian rhythm, such as chronic inflammation. 

PMID- 24582615
TI  - Swertiamarin attenuates inflammation mediators via modulating NF-kappaB/I kappaB
      and JAK2/STAT3 transcription factors in adjuvant induced arthritis.
AB  - Rheumatoid arthritis (RA) is an autoimmune and chronic inflammatory disease that
      leads to pannus formation followed by severe joint destruction, characterized by
      synovial hyperplasia, inflammation and angiogenesis. Swertiamarin is a
      secoiridoid glycoside that is used as an anti-inflammatory compound, mainly found
      in Enicostema axillare (Lam) A. Raynal, a medicinal plant used in Indian system
      of traditional medicine. In the present study, the effect of swertiamarin was
      evlauated in experimental adjuvant arthritis animal model by the estimation of
      biochemical (paw thickness, lysosomal enzymes, and urinary degradative products)
      parameters, proinflammatory cytokines and enzymes along with histopathological
      and radiographic observations. The proteins of phosphorylated NF-kappaB/IkappaB
      and JAK2/STAT3 transcription factors were also quantified from experimental
      animals as well as LPS induced RAW 264.7 macrophage cells. In in silico analysis,
      swertiamarin was docked with proinflammatory enzymes to confirm its potential.
      The administration of swertiamarin (2, 5, 10mg/kg bw) significantly (P?0.05)
      inhibited the levels of paw thickness, lysosomal enzymes and increased the body
      weight of experimental animals in a dose dependent manner. In molecular analysis,
      the treatment decreased the release of proinflammatory cytokines (IL1, TNF, IL-6)
      and proangiogenic enzymes (MMPs, iNOS, PGE2, PPARgamma and COX-2); and also
      significantly (P?0.05) increased the levels of antiinflammatory proteins (IL-10,
      IL-4) when compared to the disease groups. The swertiamarin treatment
      significantly (P?0.05) inhibited the release of NF-kappaB p65, p-IkappaBalpha, p
      JAK2 and p-STAT3 signaling proteins levels on both experimental animals and LPS
      induced cells. Histopathological and radiological analysis evidenced the curative
      effect of swertiamarin on bone destruction. The docking studies of swertiamarin
      on proinflammatory enzymes supported the results from the in vivo experiments.
      Thus the swertiamarin inhibited the development of arthritis by modulating NF
      kappaB/IkappaB and JAK2/STAT3 signaling. These findings suggested that
      swertiamarin acted as an anti-rheumatic agent. 

PMID- 24582616
TI  - Cognition in patients with burn injury in the inpatient rehabilitation
      population.
AB  - OBJECTIVE: To analyze potential cognitive impairment in patients with burn injury
      in the inpatient rehabilitation population. DESIGN: Rehabilitation patients with
      burn injury were compared with the following impairment groups: spinal cord
      injury, amputation, polytrauma and multiple fractures, and hip replacement.
      Differences between the groups were calculated for each cognitive subscale item
      and total cognitive FIM. Patients with burn injury were compared with the other
      groups using a bivariate linear regression model. A multivariable linear
      regression model was used to determine whether differences in cognition existed
      after adjusting for covariates (eg, sociodemographic factors, facility factors,
      medical complications) based on previous studies. SETTING: Inpatient
      rehabilitation facilities. PARTICIPANTS: Data from Uniform Data System for
      Medical Rehabilitation from 2002 to 2011 for adults with burn injury (N=5347)
      were compared with other rehabilitation populations (N=668,816). INTERVENTIONS:
      Not applicable. MAIN OUTCOME MEASURES: Comparison of total cognitive FIM scores
      and subscales (memory, verbal comprehension, verbal expression, social
      interaction, problem solving) for patients with burn injury versus other
      rehabilitation populations. RESULTS: Adults with burn injuries had an average
      total cognitive FIM score +/- SD of 26.8+/-7.0 compared with an average FIM score
      +/- SD of 28.7+/-6.0 for the other groups combined (P<.001). The subscale with
      the greatest difference between those with burn injury and the other groups was
      memory (5.1+/-1.7 compared with 5.6+/-1.5, P<.001). These differences persisted
      after adjustment for covariates. CONCLUSIONS: Adults with burn injury have worse
      cognitive FIM scores than other rehabilitation populations. Future research is
      needed to determine the impact of this comorbidity on patient outcomes and
      potential interventions for these deficits.

PMID- 24582618
TI  - Scales to assess gross motor function in stroke patients: a systematic review.
AB  - OBJECTIVE: To assess the clinical and psychometric properties of stroke motor
      assessment scales. DATA SOURCES: The databases consulted for the literature
      research were MEDLINE, PEDro, ISI Web of Knowledge, and Cumulative Index to
      Nursing and Allied Health (CINAHL). The search was carried out between March 2011
      and January 2014. STUDY SELECTION: Studies that describe and validate a
      measurement scale designed to assess gross motor function in stroke. The articles
      were classified according to the levels of evidence and grades of recommendation
      for diagnosis studies of the Oxford Center for Evidence-Based Medicine. DATA
      EXTRACTION: General characteristics of the studies, including number of patients,
      motor function assessment scales analyzed, and their psychometric properties,
      were collected. DATA SYNTHESIS: After the literature search, 19 articles were
      included in this review; 32 articles were excluded for not meeting the inclusion
      criteria. Four of the 19 articles studied the Motor Assessment Scale, 5 the Fugl
      Meyer Assessment, 3 investigated the Sodring Motor Evaluation for Stroke
      Patients, 4 the Stroke Rehabilitation Assessment of Movement, 2 were about the
      Motricity Index, and 2 about the Rivermead Motor Assessment. All of them were
      classified as level 2b according to the levels of evidence and grades of
      recommendation. CONCLUSIONS: All the scales compiled in this review have been
      shown to be useful both in clinical practice and in terms of research. The most
      suitable scales to be used in the clinical field would be the short versions of
      the Fugl-Meyer Assessment and the Stroke Rehabilitation Assessment of Movement. A
      real consensus about the measurement of gross motor function in patients with
      stroke is not available in the recent literature.

PMID- 24582617
TI  - Plantarflexor weakness negatively impacts walking in persons with multiple
      sclerosis more than plantarflexor spasticity.
AB  - OBJECTIVES: To determine whether plantarflexor (PF) spasticity or ankle strength
      best predicts variance in walking capacity or self-perceived limitations in
      walking in persons with multiple sclerosis (MS) and whether persons with MS with
      PF spasticity are weaker and have greater walking dysfunction than do persons
      with MS without PF spasticity. DESIGN: Cross-sectional study. SETTING: University
      research laboratory. PARTICIPANTS: Forty-two adults with MS (mean age, 42.9+/
      10.1y; Expanded Disability Status Scale score, median=3.0, range=0-6) and 14
      adults without disability (mean age, 41.9+/-10.1y). INTERVENTION: Not applicable.
      MAIN OUTCOME MEASURES: PF spasticity and dorsiflexion and PF maximum voluntary
      isometric torque were assessed using the modified Ashworth Scale and a
      computerized dynamometer, respectively. The Timed 25-Foot Walk Test was the
      primary outcome measure of walking capacity. Secondary measures included the 6
      Minute Walk Test and the 12-item Multiple Sclerosis Walking Scale. RESULTS: PF
      strength was the most consistent predictor of variance in walking capacity (Timed
      25-Foot Walk Test: R(2) change=.23-.29, P<=.001; 6-Minute Walk Test: R(2)
      change=.12-.29, P<=.012), and self-perceived limitations of walking (12-item
      Multiple Sclerosis Walking Scale: R(2) change=.04-.14, P<.18). There were no
      significant differences (P>.05) between persons with MS with PF spasticity and
      persons with MS without PF spasticity for any of the outcome measures.
      CONCLUSIONS: Our study suggests a unique contribution of PF weakness to walking
      dysfunction in persons with MS, and highlights the importance of evaluating PF
      strength in this clinical population.

PMID- 24582619
TI  - Spatial-temporal gait variability poststroke: variations in measurement and
      implications for measuring change.
AB  - OBJECTIVE: To determine the responsiveness to change of spatial-temporal gait
      parameters among stroke survivors for 3 different variability measures: SD,
      coefficient of variation (CV), and median absolute deviation (MAD). DESIGN:
      Retrospective chart review. SETTING: Clinical laboratory in a Canadian hospital.
      PARTICIPANTS: Stroke survivors (N=74) receiving inpatient rehabilitation.
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Spatial-temporal gait
      variability was calculated for step length, step width, stance time, swing time,
      and double support time. Responsiveness to change was determined by comparing (1)
      trials without versus trials with a concurrent cognitive task and (2) admission
      to discharge from rehabilitation. RESULTS: Variability estimators (SD, CV, and
      MAD) increased with the addition of a cognitive task and decreased from admission
      to discharge of rehabilitation. However, these changes were not statistically
      significant when change in gait velocity was included as a covariate. The effect
      size values were similar for all variability estimators with a trend toward a
      greater SD response to temporal parameters. The CV displayed a larger response to
      change for step length than did the SD and MAD. Although gait variability
      decreased between admission and discharge, the effect size was larger for the
      condition without the cognitive task than for the condition with the cognitive
      task. CONCLUSIONS: Our results show that gait variability estimators demonstrate
      a similar responsiveness to a concurrent cognitive task and improved walking
      ability with recovery from stroke. Future work may focus on evaluating the
      clinical utility of these measures in relation to informing therapy and response
      to gait-specific training protocols.

PMID- 24582620
TI  - Effect of Reiki therapy on pain and anxiety in adults: an in-depth literature
      review of randomized trials with effect size calculations.
AB  - The objective of this study was to calculate the effect of Reiki therapy for pain
      and anxiety in randomized clinical trials. A systematic search of PubMed,
      ProQuest, Cochrane, PsychInfo, CINAHL, Web of Science, Global Health, and Medline
      databases was conducted using the search terms pain, anxiety, and Reiki. The
      Center for Reiki Research also was examined for articles. Studies that used
      randomization and a control or usual care group, used Reiki therapy in one arm of
      the study, were published in 2000 or later in peer-reviewed journals in English,
      and measured pain or anxiety were included. After removing duplicates, 49
      articles were examined and 12 articles received full review. Seven studies met
      the inclusion criteria: four articles studied cancer patients, one examined post
      surgical patients, and two analyzed community dwelling older adults. Effect sizes
      were calculated for all studies using Cohen's d statistic. Effect sizes for
      within group differences ranged from d = 0.24 for decrease in anxiety in women
      undergoing breast biopsy to d = 2.08 for decreased pain in community dwelling
      adults. The between group differences ranged from d = 0.32 for decrease of pain
      in a Reiki versus rest intervention for cancer patients to d = 4.5 for decrease
      in pain in community dwelling adults. Although the number of studies is limited,
      based on the size Cohen's d statistics calculated in this review, there is
      evidence to suggest that Reiki therapy may be effective for pain and anxiety.
      Continued research using Reiki therapy with larger sample sizes, consistently
      randomized groups, and standardized treatment protocols is recommended. 

PMID- 24582621
TI  - Tool for Evaluating the Ways Nurses Assess Pain (TENAP): psychometric properties
      assessment.
AB  - Elderly people with cognitive impairment are at risk for under-treatment of pain
      due to their inability to communicate. Poor knowledge and attitudes of nurses
      toward pain in this population may result in inadequate pain assessment. This
      study used a descriptive correlational design to develop and validate a tool to
      assess nurses' knowledge, attitudes, and reported practice of pain assessment in
      cognitively impaired elderly patients in acute care settings. The Tool for
      Evaluating the ways Nurses Assess Pain (TENAP) has two sections: (1) nurses'
      knowledge and attitudes about pain assessment and management and (2) two
      vignettes to assess reported practice. Content validity was established by an
      expert panel of three geriatric-trained nurse clinicians, and pilot tested with a
      convenience sample of 10 nurses. The psychometric properties were tested with a
      sample of 263 Registered and Enrolled nurses working in medical wards of two
      public hospitals in Singapore. The final version of TENAP comprised 29 items.
      Content validity index ranged from 0.84 to 1.00. The scale took 10 to 15 minutes
      to complete and items were easily understood. Results from the factor analysis
      suggested that Section A demonstrated one factor (13 items) while Section B had
      two distinct factors (16 items), one for each vignette, supporting construct
      validity of the scale. Cronbach's alphas for all factors were acceptable. TENAP
      was feasible, valid, and reliable for assessing nurses' knowledge, attitudes, and
      reported practice of pain assessment in cognitively-impaired elderly patients.
      Further testing of the tool with a larger sample of nurses in other practice
      contexts is needed. 

PMID- 24582623
TI  - Preface.

PMID- 24582624
TI  - Native and recombinant Pg-AMP1 show different antibacterial activity spectrum but
      similar folding behavior.
AB  - Glycine-rich proteins (GRPs) derived from plants compose a family of proteins and
      peptides that share a glycine repeat domain and they can perform diverse
      functions. Two structural conformations have been proposed for GRPs: glycine
      loops arranged as a Velcro and an anti-parallel beta-sheet with several beta
      strands. The antimicrobial peptide Pg-AMP1 is the only plant GRP with
      antibacterial activity reported so far and its structure remains unclear.
      Recently, its recombinant expression was reported, where the recombinant peptide
      had an additional methionine residue at the N-terminal and a histidine tag at the
      C-terminal (His6-tag). These changes seem to change the peptide's activity,
      generating a broader spectrum of antibacterial activity. In this report, through
      ab initio molecular modelling and molecular dynamics, it was observed that both
      native and recombinant peptide structures were composed of an N-terminal alpha
      helix and a dynamic loop that represents two-thirds of the protein. In contrast
      to previous reports, it was observed that there is a tendency to adopt a globular
      fold instead of an extended one, which could be in both, glycine loops or anti
      parallel beta-sheet conformation. The recombinant peptide showed a slightly
      higher solvated potential energy compared to the native form, which could be
      related to the His6-tag exposition. In fact, the His6-tag could be mainly
      responsible for the broader spectrum of activity, but it does not seem to cause
      great structural changes. However, novel studies are needed for a better
      characterization of its pharmacological properties so that in the future novel
      drugs may be produced based on this peptide. 

PMID- 24582622
TI  - A novel mutation in the thyroglobulin gene that causes goiter and dwarfism in
      Wistar Hannover GALAS rats.
AB  - Outbred stocks of rats have been used extensively in biomedical, pharmaceutical
      and/or toxicological studies as a model of genetically heterogeneous human
      populations. One of such stocks is the Wistar Hannover GALAS rat. However, the
      colony of Wistar Hannover GALAS rat has been suspected of keeping a problematic
      mutation that manifests two distinct spontaneous abnormalities, goiter and
      dwarfism, which often confuses study results. We have successfully identified the
      responsible mutation, a guanine to thymine transversion at the acceptor site (3'
      end) of intron 6 in the thyroglobulin (Tg) gene (Tgc.749-1G>T), that induces a
      complete missing of exon 7 from the whole Tg transcript by mating experiments and
      subsequent molecular analyses. The following observations confirmed that Tgc.749
      1G>T/Tgc.749-1G>T homozygotes manifested both dwarfism and goiter, while Tgc.749
      1G>T/+ heterozygotes had only a goiter with normal appearance, suggesting that
      the mutant phenotypes inherit as an autosomal semi-dominant trait. The mutant
      phenotypes, goiter and dwarfism, mimicked those caused by typical endocrine
      disrupters attacking the thyroid. Hence a simple and reliable diagnostic
      methodology has been developed for genomic DNA-based genotyping of animals. The
      diagnostic methodology reported here would allow users of Wistar Hannover GALAS
      rats to evaluate their study results precisely by carefully interpreting the data
      obtained from Tgc.749-1G>T/+ heterozygotes having externally undetectable
      thyroidal lesions.

PMID- 24582625
TI  - The investigation of membrane binding by amphibian peptide agonists of CCK2R
      using (31)P and (2)H solid-state NMR.
AB  - It has been proposed that some neuropeptides may be anchored to the cell
      membranes prior to attaching to the adjacent active sites of transmembrane
      receptors. The three amphibian skin neuropeptides signiferin 1 [RLCIPYIIPC(OH)]
      (smooth muscle active and immunomodulator), riparin 1.1 [[RLCIPVIFPC(OH)]
      (immunomodulator) and rothein 1 [SVSNIPESIGF(OH)] (immunomodulator) act via CCK2
      transmembrane receptors. A combination of (31)P and (2)H solid state NMR studies
      of each of these three peptides in eukaryotic phospholipid models at 25 degrees C
      shows that rothein 1 does not interact with the membrane at all. In contrast,
      both of the cyclic disulfides signiferin 1 and riparin 1.1 interact with
      phospholipid head groups and partially penetrate into the upper leaflet of the
      model bilayer, but to different extents. These interactions are not sufficiently
      effective to cause disruption of the lipid bilayer since the peptides are not
      antimicrobial, anticancer, antifungal nor active against enveloped viruses. 

PMID- 24582627
TI  - Low pneumoperitoneum pressure reduces pain after mini-laparoscopic hysterectomy:
      results from two independent randomized controlled trails.

PMID- 24582626
TI  - Fluvoxamine moderates reduced voluntary activity following chronic dexamethasone
      infusion in mice via recovery of BDNF signal cascades.
AB  - Major depression is a complex disorder characterized by genetic and environmental
      interactions. Selective serotonin reuptake inhibitors (SSRIs) effectively treat
      depression. Neurogenesis following chronic antidepressant treatment activates
      brain derived neurotrophic factor (BDNF) signaling. In this study, we analyzed
      the effects of the SSRI fluvoxamine (Flu) on locomotor activity and forced-swim
      behavior using chronic dexamethasone (cDEX) infusions in mice, which engenders
      depression-like behavior. Infusion of cDEX decreased body weight and produced a
      trend towards lower locomotor activity during darkness. In the forced-swim test,
      cDEX-mice exhibited increased immobility times compared with mice administered
      saline. Flu treatment reversed decreased locomotor activity and mitigated forced
      swim test immobility. Real-time polymerase chain reactions using brain RNA
      samples yielded significantly lower BDNF mRNA levels in cDEX-mice compared with
      the saline group. Endoplasmic reticulum stress-associated X-box binding protein-1
      (XBP1) gene expression was lower in cDEX-mice compared with the saline group.
      However, marked expression of the XBP1 gene was observed in cDEX-mice treated
      with Flu compared with mice given saline and untreated cDEX-mice. Expression of 5
      HT2A and Sigma-1 receptors decreased after cDEX infusion compared with the saline
      group, and these decreases normalized to control levels upon Flu treatment. Our
      results indicate that the Flu moderates reductions in voluntary activity
      following chronic dexamethasone infusions in mice via recovery of BDNF signal
      cascades. 

PMID- 24582628
TI  - Large uterine cervical adenomyoma excised by vaginal approach: case report,
      images, and literature review.
AB  - Uterine adenomyoma is often overlooked, and cervical adenomyoma is extremely
      rare. Previous reports suggest that a uterine adenomyoma usually occurs in the
      uterine corpus but rarely in the uterine cervix. Approximately 20 reports of
      cervical adenomyoma have been published to date. However, cervical adenomyoma has
      been rarely investigated using magnetic resonance imaging. We encountered a large
      multicystic tumor in the uterine cervix of a 26-year-old woman that was difficult
      to diagnose preoperatively. On the basis of cytology, biopsy, and imaging
      findings, the cervical multicystic tumor measured approximately 13.0 cm. The
      patient underwent vaginal adenomyomectomy, and the tumor was completely resected.
      A histologic diagnosis of cervical adenomyoma was made because of proliferation
      of endocervical glands and the presence of rounded smooth muscle stroma.
      Awareness of this tumor in the uterine cervix is important for accurate diagnosis
      and treatment. Herein we present a rare case of a large cervical adenomyoma, with
      imaging studies, an image of the operation, histologic findings, and a literature
      review.

PMID- 24582630
TI  - Gauche(+) side-chain orientation as a key factor in the search for an immunogenic
      peptide mixture leading to a complete fully protective vaccine.
AB  - Topological and stereo-electron characteristics are essential in major
      histocompability class II-peptide-T-cell receptor (MHC-p-TCR) complex formation
      for inducing an appropriate immune response. Modified high activity binding
      peptides (mHABPs) were synthesised for complete full protection antimalarial
      vaccine development producing a large panel of individually fully protection
      inducing protein structures (FPIPS) and very high long-lasting antibody-inducing
      (VHLLAI) mHABPs. Most of those which did not interfere, compete, inhibit or
      suppress their individual VHLLAI or FPIPS activity contained or displayed a
      polyproline II-like (PPIIL) structure when mixed. Here we show that amino acid
      side-chains located in peptide binding region (PBR) positions p3 and p7 displayed
      specific electron charges and side-chain gauche(+) orientation for interacting
      with the TCR. Based on the above, and previously described physicochemical
      principles, non-interfering, long-lasting, full protection-inducing, multi
      epitope, multistage, minimal subunit-based chemically synthesised mHABP mixtures
      can be designed for developing vaccines against diseases scourging humankind,
      malaria being one of them. 

PMID- 24582629
TI  - Combined cystoscopic and laparoscopic approach in deep endometriosis of the
      bladder.
AB  - STUDY OBJECTIVE: To report the combined cystoscopic and laparoscopic approach in
      deep endometriosis with full-thickness infiltration of the bladder. DESIGN: Video
      (Canadian Task Force classification III). SETTING: University hospital. PATIENT:
      A 34-year-old nulliparous woman with a large (35-mm) endometriosis nodule
      infiltrating the bladder and deep endometriosis of the rectum and sigmoid colon.
      INTERVENTION: The urologic surgeon performed cystoscopy, identified the limits of
      mucosal involvement, and incised the muscular layer up to fat tissues surrounding
      the bladder. The gynecologic surgeon identified and followed the circular
      incision, and completed full-thickness resection of the bladder wall. Surgical
      technique reports in anonymous patients are exempt from ethical approval by the
      institutional review board. MEASUREMENTS AND MAIN RESULTS: The patient's
      functional outcome was uneventful. Laparoscopic resection of large endometriotic
      nodules of the bladder per se may lead to inadvertent removal of healthy bladder
      muscle. Thus it increases the risk of postoperative complications and symptoms
      due to small bladder volume. Conversely, if resection of the nodule is performed
      only cystoscopically, it probably would not be completely removed. We routinely
      combine the 2 approaches because this enables complete resection of the
      endometriotic nodule. It not only averts the risk of excessive removal of healthy
      bladder muscle but also leaves no disease behind. CONCLUSIONS: On the basis of
      our experience, we propose the combined cystoscopic and laparoscopic approach in
      managing large endometriotic nodules with full-thickness infiltration of the
      bladder.

PMID- 24582631
TI  - Long-lasting humoral and cellular immune responses elicited by immunization with
      recombinant chimeras of the Plasmodium vivax circumsporozoite protein.
AB  - The circumsporozoite protein (CSP), the most abundant surface antigen of
      sporozoites, has been extensively studied in different expression platforms as a
      vaccine candidate. Clinical trials have shown the necessity of broad and highly
      avid humoral immune responses together with high numbers of CSP-specific TCD4+
      and TCD8+ cells, especially those producing IFN-gamma, to induce protection. To
      this aim, we designed two distinct recombinant immunogens based on previously
      described antigenic fragments of Plasmodium vivax CSP (PvCSP) to be used as
      vaccine candidates. The first one is a virus-like particle (VLP) comprising the
      repeat region of PvCSP (B and TCD4+ epitopes) within the loop of the hepatitis B
      virus core antigen (HBcAgPvCSP). The second one is a PvCSP multi-epitope
      polypeptide, rPvCSP-ME, designed based on antigenic regions of PvCSP recognized
      by lymphocytes of individuals from endemic areas. Mice immunized with 2 doses of
      these proteins, administered individually or combined and formulated in Montanide
      ISA 720 adjuvant, were able to induce strong effector and memory humoral
      responses with IgG titers ranging from 10(4) to 10(5) and avidity indexes toward
      full-length PvCSP reaching up to 66%, even 3 months after the last immunization.
      Furthermore, balanced Th1/Th2 responses were generated, as determined by titers
      of IgG subclasses and further confirmed by ELISPOT analyses, which detected that
      these vaccination protocols were able to elicit long-term IFN-gamma and IL-2
      secreting memory T-cells. Overall, these results show that our vaccine candidates
      generate, in mice, immune responses against regions within PvCSP that have been
      associated with protection against malaria in humans. 

PMID- 24582632
TI  - WHO recommendations for the viruses used in the 2013-2014 Northern Hemisphere
      influenza vaccine: Epidemiology, antigenic and genetic characteristics of
      influenza A(H1N1)pdm09, A(H3N2) and B influenza viruses collected from October
      2012 to January 2013.
AB  - In February the World Health Organisation (WHO) recommends influenza viruses to
      be included in influenza vaccines for the forthcoming winter in the Northern
      Hemisphere. These recommendations are based on data collected by National
      Influenza Centres (NICs) through the WHO Global Influenza Surveillance and
      Response System (GISRS) and a more detailed analysis of representative and
      potential antigenically variant influenza viruses from the WHO Collaborating
      Centres for Influenza (WHO CCs) and Essential Regulatory Laboratories (ERLs).
      This article provides a detailed summary of the antigenic and genetic properties
      of viruses and additional background data used by WHO experts during development
      of the recommendations of the 2013-2014 Northern Hemisphere influenza vaccine
      composition. 

PMID- 24582633
TI  - Unless changes are made in Benin, multiple storage and transport bottlenecks may
      prevent vaccines from reaching the population.

PMID- 24582634
TI  - Is influenza-like illness a useful concept and an appropriate test of influenza
      vaccine effectiveness?
AB  - PURPOSE: To assess the utility of "influenza-like illness" (ILI) and whether it
      appropriately tests influenza vaccine effectiveness. PRINCIPAL RESULTS: The WHO
      and CDC definitions of "influenza-like illness" are similar. However many studies
      use other definitions, some not specifying a temperature and requiring specific
      respiratory and/or systemic symptoms, making many samples non-comparable. Most
      ILI studies find less than 25% of cases are RT-PCR-positive, those which test for
      other viruses and bacteria usually find multiple other pathogens, and most
      identify no pathogen in about 50% of cases. ILI symptom and symptom combinations
      do not have high sensitivity or specificity in identifying PCR-positive influenza
      cases. Rapid influenza diagnostic tests are increasingly used to screen ILI cases
      and they have low sensitivity and high specificity when compared to RT-PCR in
      identifying influenza. MAIN CONCLUSIONS: The working diagnosis of ILI presumes
      influenza may be involved until proven otherwise. Health care workers would
      benefit by renaming the WHO and CDC ILI symptoms and signs as "acute respiratory
      illness" and also using the WHO acute severe respiratory illness definition if
      the illness is severe and meets this criterion. This renaming would shift
      attention to identify the viral and bacterial pathogens in cases and epidemics,
      identify new pathogens, implement vaccination plans appropriate to the identified
      pathogens, and estimate workload during the viral season. Randomised controlled
      trials testing the effectiveness of influenza vaccine require all participants to
      be assessed by a gold standard (RT-PCR). ILI has no role in measuring influenza
      vaccine effectiveness. ILI is well established in the literature and in the
      operational definition of many surveillance databases and its imprecise
      definition may be inhibiting progress in research and treatment. The current ILI
      definition could with benefit be renamed "acute respiratory illness," with
      additional definitions for "severe acute respiratory illness" (SARI) with RT-PCR
      testing for pathogens to facilitate prevention and treatment.

PMID- 24582635
TI  - Immunization with genetically attenuated P. falciparum parasites induces long
      lived antibodies that efficiently block hepatocyte invasion by sporozoites.
AB  - Whole-parasite malaria vaccines have shown promise in clinical trials. We
      recently reported the first human trial of a malaria vaccine based on Plasmodium
      falciparum genetically attenuated parasites (PfGAP). Herein we report for the
      first time that PfGAP induces prolonged functional humoral responses in humans.
      Six volunteers were exposed to 5 bites of PfGAP-infected mosquitoes followed by
      approximately 200 bites. Plasma collected from all volunteers 3 months after the
      last exposure efficiently inhibits invasion of hepatocytes by P. falciparum
      sporozoites. The level of inhibition observed is comparable to that attained
      using plasma collected after 4-5 intravenously administrations of high numbers of
      irradiated sporozoites, validating the potential of PfGAP malaria vaccines. Our
      data highlight the role of antibody responses in pre-erythrocytic stages of human
      malaria, and suggests that to be protective, malaria vaccines might need to
      elicit long-lasting functional antibodies in addition to cellular responses. 

PMID- 24582636
TI  - Surface protein Adr2 of Rickettsia rickettsii induced protective immunity against
      Rocky Mountain spotted fever in C3H/HeN mice.
AB  - BACKGROUND: Rickettsia rickettsii is the pathogen of Rocky Mountain spotted fever
      (RMSF), a life-threatening tick-transmitted infection. Adr2 was a surface-exposed
      adhesion protein of R. rickettsii and its immunoprotection against RMSF was
      investigated in mice. METHODS: Recombinant Adr2 (rAdr2) was used to immunize
      C3H/HeN mice, and the rickettsial loads in organs of the mice were detected after
      challenge with R. rickettsii. The levels of specific antibodies of sera from the
      immunized mice were determined and the sera from immunized mice were applied to
      neutralize R. rickettsii. Proliferation and cytokine secretion of CD4(+) and
      CD8(+) T cells isolated from R. rickettsii-infected mice were also assayed after
      rAdr2 stimulation. RESULTS: After R. rickettsii challenge, the rickettsial loads
      in spleens, livers, and lungs were significantly lower and the impairment degrees
      of these organs in rAdr2-immunized mice were markedly slighter, compared with
      those in negative control mice. The ratio of specific IgG2a/IgG1 of rAdr2
      immunized mice kept increasing during the immunization. After treatment with
      rAdr2-immunized sera, the total number of R. rickettsii organisms adhering and
      invading host cells was significantly lower than that treated with PBS-immunized
      sera. Interferon-gamma secretion by CD4(+) or CD8(+) T cells and tumor necrosis
      factor-alpha secretion by CD4(+) T cells from R. rickettsii-infected mice were
      respectively significantly greater than those from uninfected mice after rAdr2
      stimulation. CONCLUSION: Adr2 is a protective antigen of R. rickettsii.
      Protection offered by Adr2 is mainly dependent on antigen-specific cell-mediated
      immune responses, including efficient activity of CD4(+) and CD8(+) T cells to
      produce great amount of TNF-alpha and/or IFN-gamma as well as rapid increase of
      specific IgG2a, which synergistically activate and opsonize host cells to killing
      intracellular rickettsiae.

PMID- 24582637
TI  - Ex vivo T2 relaxation: associations with age-related neuropathology and
      cognition.
AB  - The transverse relaxation time constant, T(2), is sensitive to brain tissue's
      free water content and the presence of paramagnetic materials such as iron. In
      this study, ex vivo magnetic resonance imaging was used to investigate
      alterations in T(2) related to Alzheimer's disease (AD) pathology and other types
      of neuropathology common in old age, as well as the relationship between T(2)
      alterations and cognition. Cerebral hemispheres were obtained from 371 deceased
      older adults. Using fast spin-echo imaging with multiple echo times, T(2) maps
      were produced and warped to a study-specific template. Hemispheres underwent
      neuropathologic examination for identification of AD pathology and other common
      age-related neuropathologies. Voxelwise linear regression was carried out to
      detect regions of pathology-related T(2) alterations and, in separate analyses,
      regions in which T(2) alterations were linked to antemortem cognitive
      performance. AD pathology was associated with T(2) prolongation in white matter
      of all lobes and T(2) shortening in the basal ganglia and insula. Gross infarcts
      were associated with T(2) prolongation in white matter of all lobes, and in the
      thalamus and basal ganglia. Hippocampal sclerosis was associated with T(2)
      prolongation in the hippocampus and white matter of the temporal lobe. After
      controlling for neuropathology, T(2) prolongation in the frontal lobe white
      matter was associated with lower performance in the episodic, semantic, and
      working memory domains. In addition, voxelwise analysis of in vivo and ex vivo
      T(2) values indicated a positive relationship between the two, though further
      investigation is necessary to accurately translate findings of the present study
      to the in vivo case.

PMID- 24582639
TI  - Genetic variation in BIN1 gene and Alzheimer's disease risk in Han Chinese
      individuals.
AB  - Genome-wide association studies have identified the bridging integrator 1 (BIN1)
      gene as the most important genetic susceptibility locus in late-onset Alzheimer's
      disease (LOAD) after apolipoprotein E for individuals of European ancestry. To
      further characterize this association and to isolate the variants within BIN1
      contributing to LOAD in Han Chinese individuals, we conducted a 2-step design
      study in our cohort of 1133 LOAD patients and 1159 control subjects. Sequencing
      analysis identified 44 variants within BIN1. Follow-up genotyping analysis
      revealed that a novel missense mutation P318L appeared to exert risk effect for
      development of LOAD; and rs67327804 was also significantly associated with LOAD
      risk even after adjusting for age, gender, and apolipoprotein E epsilon4 status.
      Haplotype analysis confirmed that the "GA" haplotype derived from single
      nucleotide polymorphisms in rs67327804 and rs1060743 showed a 1.4-fold increased
      risk of LOAD. Our findings provided the first independent evidence that variants
      in BIN1 were significantly associated with LOAD in Han Chinese individuals. 

PMID- 24582638
TI  - Cognitive and neural signatures of the APOE E4 allele in mid-aged adults.
AB  - The apolipoprotein E (APOE) e4 allele is strongly associated with increased risk
      of cognitive impairments in older adulthood. There is also a possible link to
      enhanced cognitive performance in younger adults, and the APOE e4 allele may
      constitute an example of antagonistic pleiotropy. The aim of this work was to
      investigate the cognitive and neural (functional) effects of the APOE e4 allele
      during mid-age (45-55 years), where a transition toward cognitive deficit might
      be expected. APOE e4 carriers (e4+) were compared with non-e4 carriers (e4-) on
      tasks of sustained and covert attention and prospective memory, and functional
      magnetic resonance imaging data acquired. Performance by e4+ was equivalent or
      better than e4- on all 3 tasks, although performance benefits were less
      pronounced than in youth. Neurally, e4+ showed less task-related recruitment of
      extrastriate and parietal areas. This became more evident when neural activation
      data were compared with that of young adults acquired in a parallel study. As
      expected, mid-age participants showed more diffuse neural activation. Notable was
      the fact that e4+ showed a relative inability to recruit parietal regions as they
      aged. This was coupled with a tendency to show greater recruitment of frontal
      regions, and underactivation of extrastriate visual regions. Thus, mid-age e4+
      show a pattern of neural recruitment usually seen later in life, possibly
      reflecting the source of an accelerated aging profile that describes the e4
      genotype.

PMID- 24582642
TI  - Cesarean section scar ectopic pregnancy.

PMID- 24582641
TI  - Brain volumes and risk of cardiovascular events and mortality. The SMART-MR
      study.
AB  - Brain atrophy is a strong predictor for cognitive decline and dementia, and these
      are, in turn, associated with increased mortality in the general population.
      Patients with cardiovascular disease have more brain atrophy and a higher
      morbidity and mortality. We investigated if brain volumes on magnetic resonance
      imaging were associated with the risk of cardiovascular events and mortality in
      patients with manifest arterial disease (n = 1215; mean age 58 years). Automated
      brain segmentation was used to quantify intracranial volume, and volumes of total
      brain, sulcal cerebrospinal fluid, and ventricles. After a median follow-up of
      8.3 years, 184 patients died, 49 patients had an ischemic stroke, and 100
      patients had an ischemic cardiac complication. Smaller relative brain volumes
      increased the risk of all-cause death (hazard ratio [HR] per standard deviation
      decrease in total brain volume: 1.58, 95% confidence interval [95% CI]: 1.33
      1.88), vascular death (HR 1.69, 95% CI: 1.35-2.13), and ischemic stroke (HR 1.96,
      95% CI: 1.43-2.69), independent of cardiovascular risk factors. These results
      suggest that brain volumes are an important determinant of poor outcome in
      patients with high cardiovascular risk.

PMID- 24582640
TI  - Frontal white matter integrity in adults with Down syndrome with and without
      dementia.
AB  - Adults with Down syndrome (DS) are at high risk for developing Alzheimer's
      disease after the age of 40 years. To detect white matter (WM) changes in the
      brain linked to dementia, fractional anisotropy (FA) from diffusion tensor
      imaging was used. We hypothesized that adults with DS without dementia (DS n =
      10), DS with dementia (DSAD n = 10) and age matched non-DS subjects (CTL n = 10)
      would show differential levels of FA and an association with scores from the
      Brief Praxis Test and the Severe Impairment Battery. WM integrity differences in
      DS compared with CTL were found predominantly in the frontal lobes. Across all DS
      adults, poorer Brief Praxis Test performance correlated with reduced FA in the
      corpus callosum as well as several association tracts, primarily within
      frontoparietal regions. Our results demonstrate significantly lower WM integrity
      in DS compared with controls, particularly in the frontal tracts. DS-related WM
      integrity reductions in a number of tracts were associated with poorer cognition.
      These preliminary results suggest that late myelinating frontal pathways may be
      vulnerable to aging in DS.

PMID- 24582643
TI  - Trauma airway management.
AB  - BACKGROUND: Airway management in a trauma patient can be particularly challenging
      when both a difficult airway and the need for rapid action collide. The provider
      must evaluate the trauma patient for airway difficulty, develop an airway
      management plan, and be willing to act quickly with incomplete information.
      DISCUSSION: Thorough knowledge of airway management algorithms will assist the
      emergency physician in providing optimal care and offer a rapid and effective
      treatment plan. CONCLUSIONS: Using a case-based approach, this article reviews
      initial trauma airway management strategies along with the rationale for evidence
      based treatments.

PMID- 24582644
TI  - Parents' experiences of their premature infants' transportation from a university
      hospital NICU to the NICU at two local hospitals.
AB  - The aim of this study was to describe how the parents of premature infants
      experience the transportation of their baby from the neonatal intensive care unit
      at a university hospital (NICU-U) to such a unit at a local hospital (NICU-L).
      This descriptive qualitative study comprises interviews with nine sets of parents
      and two mothers. The qualitative content analysis resulted in one theme: living
      in uncertainty about whether the baby will survive, and three categories: being
      distanced from the baby; fearing that something would happen to the baby during
      transportation; and experiencing closeness to the baby. The results also revealed
      that the parents experienced developmental, situational and health-illness
      transitions. 

PMID- 24582645
TI  - Experienced nurses' use of non-pharmacological approaches comprise more than
      relief from pain.
AB  - This study investigated the use of, and reasoning by, experienced nurses
      regarding non-pharmacological pain approaches to care for children in hospitals,
      with the aim of increasing our understanding, and hence optimizing, these
      approaches. Three focus-group interviews with 14 experienced nurses, were
      conducted in 2009. Our findings emphasized the role of non-pharmacological
      methods in building and maintaining cooperation with the child and in caring for
      the child by individualizing the use of non-pharmacological methods. 

PMID- 24582646
TI  - Pediatric nurses' grief experience, burnout and job satisfaction.
AB  - Correlations among grief, burnout, and job satisfaction among highly satisfied
      pediatric nurses were examined using the Revised Grief Experience Inventory
      (RGEI), Maslach Burnout Inventory (MBI), and Index of Work Satisfaction (IWS).
      Results showed that grief had significant correlations; positive with burnout,
      negative with job satisfaction. RN's reported significantly higher emotional
      exhaustion if their primary patients died and higher guilt if patients died
      younger. Conclusions suggest a dynamic statistical interaction among nurses'
      grief, burnout, and job satisfaction representing a pathway to intention to leave
      their unit, organization, or nursing. Recommendations include implementation and
      evaluation of grief intervention and education programs. 

PMID- 24582647
TI  - Evaluation of a Memory Book intervention with orphaned children in South Africa.
AB  - The purpose of this collaborative research study was to evaluate the use of the
      Memory Book intervention for orphaned children's grief and loss recovery. A
      qualitative phenomenological approach was implemented to evaluate the Memory Book
      intervention with orphaned children at two children's homes in South Africa.
      Study findings support the ability of children to work through loss and grief
      when they are assisted in preserving and telling their story. The Memory Book
      intervention assists children to chronicle their lives and demonstrates the
      potential to guide future interventions by care providers and nurses in this
      context. 

PMID- 24582648
TI  - Pediatric skin integrity practice guideline for institutional use: a quality
      improvement project.
AB  - Superior skin care is a nurse-sensitive outcome measure (Young, T., & Clark, M.
      (2009). Re-positioning for pressure ulcer prevention (protocol). The Cochrane
      Database of Systematic Review (2009) 3). This study sought to decrease incidence
      and risk of skin breakdown in the pediatric cardiac intensive care unit (PCICU).
      The study was conducted in a large hospital in upstate New York. A practice
      guideline was created and guided PCICU nurses on the interventions for potential
      skin-breakdown issues in their patients. The patients had a significant change in
      skin breakdown with a one-sided Fisher's Exact Test (p=.0422). A logistic
      regression model showed intervention as a significant factor in reducing
      incidence of pressure ulcers and length of stay (p=.0389). 

PMID- 24582649
TI  - What nurses need to know about fecal microbiota transplantation: education,
      assessment, and care for children and young adults.
AB  - Fecal microbiota transplantation (FMT) is an emerging experimental therapy for
      treatment of recurrent Clostridium difficile infection. In the future, FMT has
      the potential to be a treatment modality in other diseases that involve gut
      dysbiosis. As use of FMT is likely to expand, pediatric nurses need a clear
      understanding of FMT to provide appropriate education, assessment, and care for
      these patients. Pediatric research and clinical nurses are a resource to help
      children and parents understand the procedure. Important topics include donor
      screening, patient assessment before, during, and after treatment; routes of
      administration and positioning; preparation for discharge and followup
      evaluation. 

PMID- 24582650
TI  - Evaluation of urinary speciated arsenic in NHANES: issues in interpretation in
      the context of potential inorganic arsenic exposure.
AB  - Urinary dimethylarsinic acid (DMA) and monomethylarsonic acid (MMA) are among the
      commonly used biomarkers for inorganic arsenic (iAs) exposure, but may also arise
      from seafood consumption and organoarsenical pesticide applications. We examined
      speciated urinary arsenic data from National Health and Nutrition Examination
      Survey (NHANES) 2009-2010 cycle to assess potential correlations among urinary
      DMA, MMA, and the organic arsenic species arsenobetaine. Urinary DMA and MMA were
      positively associated with urinary arsenobetaine, suggesting direct exposure to
      these species in seafood or metabolism of organic arsenicals to these species,
      although the biomonitoring data do not directly identify the sources of exposure.
      The magnitude of association was much larger for DMA than for MMA. The secondary
      methylation index (SMI, ratio of urinary DMA to MMA) observed in the NHANES
      program likewise is much higher in persons with detected arsenobetaine than in
      those without, again suggesting that direct DMA exposure is co-occurring with
      exposure to arsenobetaine. Urinary MMA was less correlated with organic arsenic
      exposures than DMA and, therefore, may be a more reliable biomarker for iAs
      exposure in the general US population. However, given the associations between
      both MMA and DMA and organic arsenic species in urine, interpretations of the
      urinary arsenic concentrations observed in the NHANES in the context of potential
      arsenic exposure should be made cautiously. 

PMID- 24582651
TI  - Human health risk evaluation of selected VOC, SVOC and particulate emissions from
      scented candles.
AB  - Airborne compounds in the indoor environment arise from a wide variety of sources
      such as environmental tobacco smoke, heating and cooking, construction materials
      as well as outdoor sources. To understand the contribution of scented candles to
      the indoor load of airborne substances and particulate matter, candle emission
      testing was undertaken in environmentally controlled small and large emission
      chambers. Candle emission rates, calculated on the basis of measured chamber
      concentrations of volatile and semi-volatile organic compounds (VOC, SVOC) and
      particulate matter (PM), were used to predict their respective indoor air
      concentrations in a standard EU-based dwelling using 2 models: the widely
      accepted ConsExpo 1-box inhalation model and the recently developed RIFM 2-box
      indoor air dispersion model. The output from both models has been used to
      estimate more realistic consumer exposure concentrations of specific chemicals
      and PM in candle emissions. Potential consumer health risks associated with the
      candle emissions were characterized by comparing the exposure concentrations with
      existing indoor or ambient air quality guidelines or, where not existent, to
      established toxicity thresholds. On the basis of this investigation it was
      concluded that under normal conditions of use scented candles do not pose known
      health risks to the consumer. 

PMID- 24582652
TI  - Diagnostic accuracy of intra-articular C-reactive protein assay in periprosthetic
      knee joint infection--a preliminary study.
AB  - BACKGROUND: Periprosthetic joint infection often raises diagnostic challenges, as
      the published criteria are heterogeneous. New markers for predicting
      periprosthetic infection have been evaluated. Here, we assessed one of these
      markers, C-reactive protein (CRP), in joint fluid. HYPOTHESIS: We hypothesised
      that intra-articular CRP levels would perform better than serum CRP
      concentrations in diagnosing knee prosthesis infection. PATIENTS AND METHODS: We
      prospectively included 30 patients including 10 with native-knee effusions, 11
      with prosthetic-knee aseptic effusions, and 11 with prosthetic-knee infection
      defined using 2011 Musculoskeletal Society criteria. Serum CRP was assayed using
      turbidimetry or nephelometry and intra-articular CRP using nephelometry.
      Appropriate statistical tests were performed to compare the three groups; P
      values < 0.05 were considered significant. RESULTS: Serum and intra-articular CRP
      levels were 5- to 16-fold higher in the group with periprosthetic infection than
      in the other two groups. Although the areas under the ROC curves were not
      significantly different, the likelihood ratios associated with the selected cut
      offs suggested superiority of intra-articular CRP: a value > 2.78 mg/L suggested
      possible infection (100% sensitivity and 82% specificity) and a value > 5.37 mg/L
      probable infection (90% sensitivity and 91% specificity). DISCUSSION: Our
      findings suggest a possible role for intra-articular CRP assay in diagnosing knee
      prosthesis infection and perhaps periprosthetic infection at any site. LEVEL OF
      EVIDENCE: Level III, diagnostic study, development of a diagnostic criterion in
      consecutive patients comparatively to a reference standard.

PMID- 24582653
TI  - Identification of novel mutations of PKD1 gene in Chinese patients with autosomal
      dominant polycystic kidney disease by targeted next-generation sequencing.
AB  - BACKGROUND: Mutations of PKD1 and PKD2 accounted for the most cases of autosomal
      dominant polycystic kidney disease (ADPKD). The presence of the large transcript,
      numerous exons and complex reiterated regions within the gene has significantly
      complicated the analysis of PKD1 with routine PCR-based approaches. METHODS: We
      developed a strategy to analyze both the PKD1/PKD2 genes simultaneously using
      targeted next-generation sequencing (NGS). All coding exons plus the flanking
      sequences of PKD1 and PKD2 genes from probands were captured, individually
      barcoded and followed by HiSeq2000 sequencing. The candidate variants were
      validated by using classic Sanger sequencing. PKD1-specific primers were designed
      to amplify the replicated areas of PKD1 gene. RESULTS: Five novel variations and
      one known mutation in PKD1 gene were detected in five familial and one sporadic
      Chinese ADPKD patients. Through pedigree and bioinformatic analysis, five of them
      were identified as pathogenic mutations (p.G1319R, p.Y3781*, p.W4122*,
      p.Val700Glyfs*14, and p.Leu3656Trpfs*28) and one was as polymorphism (p.T2420I).
      CONCLUSIONS: Our result showed that targeted capture and NGS technology were
      effective for the gene testing of ADPKD disorder. Mutation study of PKD1 and PKD2
      genes in Chinese patients may contribute to better understanding of the genetic
      diversity between different ethnic groups and enrich the mutation database in
      Asian population.

PMID- 24582654
TI  - Development of reference materials to detect 15 different human papillomavirus
      genotypes.
AB  - Accurate human papillomavirus (HPV) typing is essential for evaluating and
      monitoring HPV vaccines in cervical cancer screening and in epidemiological
      surveys. In our country, different HPV DNA detection and genotyping methodologies
      have been established for diagnosing and monitoring HPV-related disease in
      clinical practice and for research. However, there is a lack of reference
      materials to standardize the methods for HPV detection and genotyping. In this
      study, we constructed candidate reference materials comprising 15 targets (13
      types of high-risk HPV, two types of low-risk HPV). We evaluated whether the
      candidate reference materials could be used as the reference for HPV detection
      and genotyping using quantitative real-time polymerase chain reaction. Standard
      curves for the wide linear range (10(1)-10(6)copies/MUL) produced high
      correlation regression coefficient R(2) of 0.99. The reaction efficiencies were
      96.3% to 101.2% for the standard curves, indicating highly efficient reactions.
      Specific genotypes were detected in single or multiple mixed samples. Our results
      suggest that these reference materials may provide useful standards for
      standardizing quality assurance for different HPV-typing assays and for
      proficiency testing in diagnostic laboratories. 

PMID- 24582655
TI  - Membrane-bound delta-like 1 homolog (Dlk1) promotes while soluble Dlk1 inhibits
      myogenesis in C2C12 cells.
AB  - Delta-like 1 homolog (Dlk1) is important in myogenesis. However, the roles of
      different Dlk1 isoforms have not been investigated. In C2C12 cell lines producing
      different Dlk1 isoforms, membrane-bound Dlk1 promoted the hypertrophic phenotype
      and a higher fusion rate, whereas soluble Dlk1 inhibited myotube formation.
      Inversed expression patterns of genes related to myogenic differentiation further
      support these phenotypic changes. In addition, temporal expression and balance
      between the Dlk1 isoforms have a regulatory role in myogenesis in vivo.
      Collectively, Dlk1 isoforms have distinctive effects on myogenesis, and its
      regulation during myogenesis is critical for normal muscle development. 

PMID- 24582656
TI  - Rpi-blb2-mediated late blight resistance in Nicotiana benthamiana requires SGT1
      and salicylic acid-mediated signaling but not RAR1 or HSP90.
AB  - The Rpi-blb2 recognizes the presence of the Phytophthora infestans AVRblb2 and
      initiates effector-triggered immunity (ETI). We performed gain-of-function and
      loss-of-function studies in Nicotiana benthamiana to elucidate Rpi-blb2-mediated
      resistance to P. infestans. Rpi-blb2 triggered a hypersensitive response through
      SGT1-mediated, but not RAR-mediated or HSP90-mediated, pathways. NbSGT1 was also
      required for basal and ETI-mediated by Rpi-blb2 in N. benthamiana. Moreover,
      salicylic acid (SA) affected basal defense and Rpi-blb2-mediated resistance
      against P. infestans. The increased susceptibility of Rpi-blb2-transgenic plants
      in the NahG-background correlated with reduced levels of SA. These findings
      provide evidence for the roles of SGT1- and SA-signaling in Rpi-blb2-mediated
      resistance against P. infestans. 

PMID- 24582657
TI  - Addressing student and schooling problems: not another project! Child safety
      should be embedded in the missions of schools.

PMID- 24582658
TI  - The relationship between adult health and childhood maltreatment, as moderated by
      anger and ethnic background.
AB  - Childhood maltreatment, anger, and racial/ethnic background were examined in
      relation to physical health, psychological well-being, and blood pressure
      outcomes. This study used data from a diverse sample of African American, Latino,
      and Caucasian participants (N=198). Results from a series of multiple regressions
      indicated anger and total childhood maltreatment were robust predictors of poorer
      health. Although correlational analyses found maltreatment from the mother and
      father were associated with poorer health outcomes, when considered as part of
      the regression models, only a relationship between maltreatment from the mother
      and physical health was found. Greater anger scores were linked with lower blood
      pressure, particularly systolic blood pressure. Generally, more psychological and
      physical symptom reporting was found with greater anger scores, and higher levels
      of total maltreatment also predicted physical symptoms. The pattern of
      interactions indicated anger was more detrimental for African American
      participant's (and marginally so for Latino participant's) physical health.
      Interestingly, interactions also indicated total childhood maltreatment was
      related to fewer symptoms for Latino participants. Although child maltreatment
      may be viewed as a moral and/or human rights issue, this study provides evidence
      that it can also be viewed as a public health issue. Our study demonstrated that
      known health risk factors such as anger and maltreatment may operate in a
      different pattern dependent on ethnic/cultural background. The findings suggest
      health and health disparities research would benefit from greater exploration of
      the differential impact of certain moderating variables based on racial/ethnic
      background. 

PMID- 24582659
TI  - Combined of ultrasound irradiation with high hydrostatic pressure (US/HHP) as a
      new method to improve immobilization of dextranase onto alginate gel.
AB  - In this research work, dextranase was immobilized onto calcium alginate beads by
      the combination of ultrasonic irradiation and high hydrostatic pressure (US/HHP)
      treatments. Effects of US/HHP treatments on loading efficiency and immobilization
      yield of dextranase enzyme onto calcium alginate beads were investigated.
      Furthermore, the activities of immobilized enzymes prepared with and without
      US/HHP treatments and that prepared with ultrasonic irradiation (US) and high
      hydrostatic pressure (HHP), as a function of pH, temperature, recyclability and
      enzyme kinetic parameters, were compared with that for free enzyme. The maximum
      loading efficiency and the immobilization yield were observed when the
      immobilized dextranase was prepared with US (40 W at 25 kHz for 15 min) combined
      with HHP (400 MPa for 15 min), under which the loading efficiency and the
      immobilization yield increased by 88.92% and 80.86%, respectively, compared to
      immobilized enzymes prepared without US/HHP treatment. On the other hand,
      immobilized enzyme prepared with US/HHP treatment showed Vmax, KM, catalytic and
      specificity constants values higher than that for the immobilized enzyme prepared
      with HHP treatment, indicated that, this new US/HHP method improved the catalytic
      kinetics activity of immobilized dextranase at all the reaction conditions
      studied. Compared to immobilized enzyme prepared either with US or HHP, the
      immobilized enzymes prepared with US/HHP method exhibited a higher: pH optimum,
      optimal reaction temperature, thermal stability and recyclability, and lower
      activation energy, which, illustrating the effectiveness of the US/HHP method.
      These results indicated that, the combination of US and HHP treatments could be
      an effective method for improving the immobilization of enzymes in polymers.

PMID- 24582660
TI  - Sonochemically synthesized mono and bimetallic Au-Ag reduced graphene oxide based
      nanocomposites with enhanced catalytic activity.
AB  - Graphene oxide (GO) supported Ag and Au mono-metallic and Au-Ag bimetallic
      catalysts were synthesized using a sonochemical method. Bimetallic catalysts
      containing different weight ratios of Au and Ag were loaded onto GO utilizing a
      low frequency horn-type ultrasonicator. High frequency ultrasonication was used
      to efficiently reduce Ag(I) and Au(III) ions in the presence of polyethylene
      glycol and 2-propanol. Transmission electron microscopy (TEM-EDX) and X-ray
      photoelectron spectroscopy were used to analyze the morphology, size, shape and
      chemical oxidation states of the prepared metallic catalysts on GO. The catalytic
      efficiency of the prepared catalysts were compared using 4-nitrophenol (4-NP)
      reduction reaction and the subsequent formation of 4-aminophenol (4-AP) that was
      also monitored using UV-vis spectrophotometry. The results revealed that Au-Ag-GO
      bimetallic catalysts showed high activity for the conversion of 4-NP to 4-AP than
      their monometallic counterparts. Amongst different weight ratios (1:1, 1:2 and
      2:1) between Au and Ag, the 1:2 (Au:Ag) catalyst exhibited very good catalytic
      performance for the conversion of 4-NP to 4-AP. A total reduction of 4-NP took
      place within a short period of time if Au-GO was reduced first followed by Ag
      reduction, whereas a lower reduction rate was observed if Ag-GO was reduced
      first. The same trend was observed for all the ratios of bimetallic catalysts
      prepared by this method. The initial unfavorable reduction potential of Ag(I) is
      likely to be responsible for the above order. It was found that applying dual
      frequency ultrasonication was a highly effective way of preparing bimetallic
      catalysts requiring relatively low levels of added chemicals and producing
      bimetallic catalysts with GO with improved catalytic efficiency. 

PMID- 24582661
TI  - The genetics of chemoreception in the labella and tarsi of Aedes aegypti.
AB  - The yellow-fever mosquito Aedes aegypti is a major vector of human diseases, such
      as dengue, yellow fever, chikungunya and West Nile viruses. Chemoreceptor organs
      on the labella and tarsi are involved in human host evaluation and thus serve as
      potential foci for the disruption of blood feeding behavior. In addition to host
      detection, these contact chemoreceptors mediate feeding, oviposition and
      conspecific recognition; however, the molecular landscape of chemoreception in
      these tissues remains mostly uncharacterized. Here we report the expression
      profile of all putative chemoreception genes in the labella and tarsi of both
      sexes of adult Ae. aegypti and discuss their possible roles in the physiology and
      behavior of this important disease vector. 

PMID- 24582662
TI  - Parallel expression of alternate forms of psbA2 gene provides evidence for the
      existence of a targeted D1 repair mechanism in Synechocystis sp. PCC 6803.
AB  - The D1 protein of Photosystem II (PSII) is recognized as the main target of
      photoinhibitory damage and exhibits a high turnover rate due to its degradation
      and replacement during the PSII repair cycle. Damaged D1 is replaced by newly
      synthesized D1 and, although reasonable, there is no direct evidence for
      selective replacement of damaged D1. Instead, it remains possible that increased
      turnover of D1 subunits occurs in a non-selective manner due for example, to a
      general up-regulation of proteolytic activity triggered during damaging
      environmental conditions, such as high light. To determine if D1 degradation is
      targeted to damaged D1 or generalized to all D1, we developed a genetic system
      involving simultaneous dual expression of wild type and mutant versions of D1
      protein. Dual D1 strains (nS345P:eWT and nD170A:eWT) expressed a wild type (WT)
      D1 from ectopic and a damage prone mutant (D1-S345P, D1-D170A) from native locus
      on the chromosome. Characterization of strains showed that all dual D1 strains
      restore WT like phenotype with high PSII activity. Higher PSII activity indicates
      increased population of PSII reaction centers with WT D1. Analysis of steady
      state levels of D1 in nS345P:eWT by immunoblot showed an accumulation of WT D1
      only. But, in vivo pulse labeling confirmed the synthesis of both S345P (exists
      as iD1) and WT D1 in the dual strain. Expression of nS345P:eWT in FtsH2 knockout
      background showed accumulation of both iD1 and D1 proteins. This demonstrates
      that dual D1 strains express both forms of D1, yet only damage prone PSII
      complexes are selected for repair providing evidence that the D1 degradation
      process is targeted towards damaged PSII complexes. Since the N-terminus has been
      previously shown to be important for the degradation of damaged D1, the
      possibility that the highly conserved cysteine 18 residue situated in the N
      terminal domain of D1 is involved in the targeted repair process was tested by
      examining site directed mutants of this and the other cysteines of the D1
      protein. This article is part of a special issue entitled: photosynthesis
      research for sustainability: keys to produce clean energy.

PMID- 24582663
TI  - Disentangling two non-photochemical quenching processes in Cyclotella
      meneghiniana by spectrally-resolved picosecond fluorescence at 77K.
AB  - Diatoms, which are primary producers in the oceans, can rapidly switch on/off
      efficient photoprotection to respond to fast light-intensity changes in moving
      waters. The corresponding thermal dissipation of excess-absorbed-light energy can
      be observed as non-photochemical quenching (NPQ) of chlorophyll a fluorescence.
      Fluorescence-induction measurements on Cyclotella meneghiniana diatoms show two
      NPQ processes: qE1 relaxes rapidly in the dark while qE2 remains present upon
      switching to darkness and is related to the presence of the xanthophyll-cycle
      pigment diatoxanthin (Dtx). We performed picosecond fluorescence measurements on
      cells locked in different (quenching) states, revealing the following sequence of
      events during full development of NPQ. At first, trimers of light-harvesting
      complexes (fucoxanthin-chlorophyll a/c proteins), or FCPa, become quenched, while
      being part of photosystem II (PSII), due to the induced pH gradient across the
      thylakoid membrane. This is followed by (partial) detachment of FCPa from PSII
      after which quenching persists. The pH gradient also causes the formation of Dtx
      which leads to further quenching of isolated PSII cores and some aggregated FCPa.
      In subsequent darkness, the pH gradient disappears but Dtx remains present and
      quenching partly pertains. Only in the presence of some light the system
      completely recovers to the unquenched state. 

PMID- 24582664
TI  - Influence of the protein status of piglets on their ability to select and prefer
      protein sources.
AB  - Pigs may have retained the capacity to choose feeds based on their nutritional
      requirements, even after decades in which they are not allowed to select their
      diet composition due to the common feeding systems of the intensive pig industry.
      We used 480 early-weaned piglets in two experiments to assess their ability to
      select and prefer protein-related sources, depending on their protein status.
      Piglets were fed after weaning with two isoenergetic diets formulated to contain
      an optimal or sub-optimal crude-protein (CP) content, a high-protein (HP, 204g
      CP/kg as-fed) or a low-protein diet (LP, 142g CP/kg), respectively. In Experiment
      1, the preference of piglets was assessed by using a choice test between protein
      (porcine digestible peptides [PDP] 40g/L) and carbohydrate (sucrose 40g/L) water
      based solutions for a period of 3min. Piglets showed higher intake and preference
      for the sucrose 40g/L than for the PDP 40g/L solution, independently of the
      dietary CP content (9.8mL/kg body weight [BW] vs. 3.7mL/kg BW and 10.4mL/kg BW
      vs. 4.3mL/kg BW in HP and LP pigs, respectively). In Experiment 2, piglets were
      given eight training sessions in which two equally preferred flavors were mixed
      with protein (porcine animal plasma 60g/L, CSp) or carbohydrate (maltodextrin
      60g/L, CSc) solutions. In the subsequent choice test, piglets fed the HP diet
      showed a tendency to a higher intake of CSc than of CSp (6.5mL/kg BW vs. 5.4mL/kg
      BW). On the other hand, piglets fed the LP diet showed a higher intake and
      preference for CSp than for CSc (15.5mL/kg BW vs. 10.2mL/kg BW), differences
      being higher for medium and low BW piglets than for heavy ones. The results show
      that piglets are unable to express a specific appetite for protein to correct
      previous underfeeding with it; however, they may show an appropriate dietary
      selection pattern in order to overcome protein deficiency through associative
      learning. 

PMID- 24582665
TI  - A mutation causing increased KATP channel activity leads to reduced anxiety in
      mice.
AB  - Activating mutations in the Kir6.2 (KCNJ11) subunit of the ATP-sensitive
      potassium channel cause neonatal diabetes. Many patients also suffer from
      neurological complications. By using mice carrying a human Kir6.2 mutation
      (Val(59) to Met(59); nV59M mice) targeted to neurones, we show that these
      mutations also result in altered anxiety behaviour. The light/dark box,
      successive alleys and elevated plus maze tasks revealed that nV59M mice have
      reduced anxiety related responses. Additionally, nV59M mice displayed enhanced
      basal locomotor activity and exploratory behaviour, as assessed by the low
      anxiety open-field test. These findings, in combination with previously reported
      hyperactivity of nV59M mice, appear to correlate with the increased impulsivity
      and inattentiveness reported in iDEND/DEND patients. 

PMID- 24582667
TI  - Anhedonia was associated with the dysregulation of hippocampal HTR4 and microRNA
      Let-7a in rats.
AB  - OBJECTIVE: Depression is a serious mental illness. However, the molecular
      mechanisms responsible for the development of depression remain unknown. METHODS:
      In this study, animal models of depression were established using maternal
      deprivation (MD) and chronic unpredictable stress (CUPS). Behavioral performance
      of rats was monitored by open field test, forced swim test, and sucrose
      consumption test. The expression of serotonin receptor-4 (Htr4) mRNA and Let-7a
      microRNA was detected by real-time PCR, while Htr4 protein level was measured by
      Western blot. RESULTS: In the open field test, rats subjected to MD and CUPS
      exhibited significant decreases in vertical activity. CUPS rats spent less time
      in the central area and excreted more fecal pellets than MD and control rats. In
      the forced swim and sucrose consumption tests, CUPS and MD rats exhibited
      significantly longer floating time and consumed less sucrose than control rats.
      MD rats exhibited significantly shorter floating time and consumed less sucrose
      than CUPS rats. MD rats showed significantly lower Htr4 mRNA and protein
      expression and significantly higher Let-7a level in the hippocampus than control
      rats. Htr4 mRNA and protein expression negatively correlated with Let-7a
      expression. Htr4 mRNA expression positively correlated with sucrose preference
      rate, while Let-7a expression negatively correlated with the sucrose preference
      rate. CONCLUSION: Anhedonia, not despair or a decline in exploratory interest,
      may be associated with upregulation of Let-7a and downregulation of Htr4
      expression in the hippocampus. The hippocampal Htr4 level may be regulated by Let
      7a in rats.

PMID- 24582668
TI  - Sleep characteristics in the quail Coturnix coturnix.
AB  - As mammals, birds exhibit two sleep phases, slow wave sleep (SWS) and REM (Rapid
      Eye Movement) sleep characterized by presenting different electrophysiological
      patterns of brain activity. During SWS a high amplitude slow wave pattern in
      brain activity is observed. This activity is substituted by a low amplitude fast
      frequency pattern during REM sleep. Common quail (Coturnix coturnix) is an animal
      model that has provided information related to different physiological mechanisms
      present in man. There are reports related to its electrophysiological brain
      activity, however the sleep characteristics that have been described are not. The
      objectives of this study is describing the sleep characteristics throughout the
      nychthemeral cycle of the common quail and consider this bird species as an avian
      model to analyze the regulatory mechanisms of sleep. Experiments were carried out
      in implanted exemplars of C. coturnix. Under general anesthesia induced by ether
      inhalation, stainless steel electrodes were placed to register brain activity
      from the anterior and posterior areas during 24 continuous hours throughout the
      sleep-wake cycle. Ocular and motor activities were visually monitored. Quail
      showed four electrophysiologically and behaviorally different states of
      vigilance: wakefulness (53.28%), drowsiness (14.27%), slow wave sleep (30.47%)
      and REM sleep (1.98%). The animals presented 202 REM sleep episodes throughout
      the nychthemeral cycle. Sleep distribution was polyphasic; however sleep amount
      was significantly greater during the period corresponding to the night. The
      number of nocturnal REM sleep episodes was significantly greater than that of
      diurnal one. CONCLUSION: The quail C. coturnix shows a polyphasic distribution of
      sleep; however the amount of this state of vigilance is significantly greater
      during the nocturnal period.

PMID- 24582669
TI  - Increase of glucocorticoid receptor expression after environmental enrichment:
      relations to spatial memory, exploration and anxiety-related behaviors.
AB  - Environmental enrichment (EE) produces a remarkable degree of structural and
      functional plasticity in the hippocampus and possible mediators of these changes,
      such as glucocorticoid receptors (GRs), are of considerable interest. GRs are
      richly expressed in the hippocampus and they are involved in the adaptation to
      stressors and facilitate active coping in anxious situations. In this study, we
      assessed the effect of an EE protocol (24h/day during 69days) in adult Wistar
      rats on the activity in the elevated-zero maze (EZM), performance in the
      holeboard task (HB) and we also examined the changes in the glucocorticoid
      receptors (GRs) expression in the dorsal hippocampus (CA1, CA3 and DG). Our EE
      protocol reduced anxious behaviors in the EZM, so the animals spent more time and
      made more entries into the open sections. In the HB task, the enriched group
      showed more explorative behavior, a reduction of anxiety-related behaviors and a
      better cognitive performance compared to non-enriched animals. With regard to the
      GR expression, the EE condition produced an increase in the number of
      immunopositive cells for GRs in CA1, CA3 and DG. These results suggest that the
      better performance of enriched animals could be mediated in part by the increase
      of GRs in the dorsal hippocampus, which may alter the hippocampal neuronal
      function and accordingly, the anxiety levels, the spatial memory performance and
      the exploration levels in these animals. 

PMID- 24582670
TI  - Panax quinquefolium involves nitric oxide pathway in olfactory bulbectomy rat
      model.
AB  - Olfactory bulbectomy (OBX) is a well known screening model for depression. Panax
      quinquefolium (PQ) is known for its therapeutic potential against several
      psychiatric disorders. Nitric oxide (NO), an intercellular messenger has been
      suggested to play a crucial role in the pathogenesis of depression. The present
      study was designed to explore the possible involvement of NO mechanism in the
      protective effect of PQ against olfactory bulbectomy induced depression. Wistar
      rats were bulbectomized surgically and kept for a rehabilitation period of two
      weeks. PQ (50, 100 and 200mg/kg; p.o.) alone and in combination with NO
      modulators like l-NAME (10mg/kg, i.p.) and l-arginine (100mg/kg; i.p.) were then
      administered daily for another two weeks. Ablation of olfactory bulbs caused
      depression-like symptoms as evidenced by increased immobility time in forced swim
      test, hyperactivity in open field arena, and anhedonic like response in sucrose
      preference test. Further, OBX caused elevation in serum corticosterone levels and
      increased oxidative-nitrosative damage. These deficits were integrated with
      increased levels of neuroinflammatory cytokines (TNF-alpha), apoptotic factor
      (caspase-3) and a marked reduction in neurogenesis factor (BDNF) in both cerebral
      cortex and hippocampal regions of bulbectomized rats. Treatment with PQ
      significantly and dose-dependently restored these behavioral, biochemical and
      molecular alterations associated with OBX. Further, pretreatment of l-NAME with
      subeffective dose of PQ (100mg/kg) significantly potentiated its protective
      effects; however l-arginine pretreatment reversed the beneficial effects. The
      present study suggests that protective effect of P. quinquefolium might involve
      nitric oxide modulatory pathway against olfactory bulbectomy-induced depression
      in rats. 

PMID- 24582666
TI  - Invoking the power of thrombospondins: regulation of thrombospondins expression.
AB  - Increasing evidence suggests critical functions of thrombospondins (TSPs) in a
      variety of physiological and pathological processes. With the growing
      understanding of the importance of these matricellular proteins, the need to
      understand the mechanisms of regulation of their expression and potential
      approaches to modulate their levels is also increasing. The regulation of TSP
      expression is multi-leveled, cell- and tissue-specific, and very precise.
      However, the knowledge of mechanisms modulating the levels of TSPs is fragmented
      and incomplete. This review discusses the known mechanisms of regulation of TSP
      levels and the gaps in our knowledge that prevent us from developing strategies
      to modulate the expression of these physiologically important proteins. 

PMID- 24582672
TI  - Long-term effects of traumatic stress on subsequent contextual fear conditioning
      in rats.
AB  - Exposure to stressful events affects subsequent sensitivity to fear. We
      investigated the long-term effects of a traumatic experience on subsequent
      contextual fear conditioning and anxiety-like behaviors in rats (Experiment 1).
      In addition, we tested whether the administration of the glucocorticoid synthesis
      inhibitor metyrapone (MET) attenuated the sensitization of fear induced by
      traumatic stress (Experiment 2). Male rats were subjected to a multiple stress
      (MS) session, which consisted of 4 foot shocks (1mA, 1s) and forced swimming for
      20min, followed by exposure to a situational reminder 7days after the MS session.
      MET (25 or 100mg/kg, intraperitoneal) was administered 30min before MS. The
      contextual fear conditioning was performed 14days after MS. MS enhanced the
      conditioned fear response for at least 14days after the conditioning, and
      pretreatment with MET did not affect the enhancement of conditioned fear. These
      results suggest that glucocorticoid secretion triggered by MS is not involved in
      regulating the long-term stress-induced sensitization of fear. 

PMID- 24582671
TI  - Post-oral fat stimulation of intake and conditioned flavor preference in C57BL/6J
      mice: A concentration-response study.
AB  - Fat appetite is determined not only by orosensory (flavor) stimuli but also by
      the post-oral actions of dietary fat, which promote increased attraction to the
      flavors of high-fat foods. Experiment 1 presents a concentration-response
      analysis of how intragastric (IG) fat self-infusions stimulate intake and
      condition flavor preferences in C57BL/6J mice trained 1h/day. Separate groups of
      food-restricted mice consumed a flavored saccharin solution (the CS-) paired with
      IG self-infusions of water (Test 0) followed by a different flavored solution
      (the CS+) paired with IG self-infusions of 1.6, 3.2, 6.4 or 12.8% Intralipid (IL,
      soybean oil) (Tests 1-3). Following additional CS- and CS+ training sessions, a
      two-bottle CS+ vs. CS- choice test was conducted without infusions. Infusions of
      3.2-12.8% IL stimulated CS+ licking in the first test session and more so in
      subsequent test sessions, and also conditioned significant CS+ preferences. These
      effects were similar to those previously observed with isocaloric glucose
      infusions (8-32%). IG infusion of 1.6% IL stimulated intake slightly but did not
      condition a CS+ preference comparable to the actions of isocaloric 4% glucose.
      Experiment 2 compared these subthreshold IL and glucose concentrations with that
      of a 1.6% IL+4% glucose infusion. This mixture stimulated 1-h CS+ licking more
      rapidly but generated a preference similar to that of 1.6% IL. In 23h/day tests,
      however, the IL+glucose mixture stimulated greater CS+ intakes and preferences
      than did 1.6% IL or 4% glucose. These findings show that fat, like glucose,
      rapidly generates concentration-dependent post-oral signals that stimulate intake
      and enhance preferences for energy-rich foods in mice. 

PMID- 24582673
TI  - Gastric and intestinal satiation in obese and normal weight healthy people.
AB  - OBJECTIVE: The gastrointestinal tract plays a key role in feelings of satiation.
      It is known that there is a reciprocal interaction between the stomach and
      intestine, but it is not known which factors are of gastric origin and which are
      intestinal. This three-step study therefore sought to provide illumination on
      satiation parameters with respect to body mass. METHOD: In the first part, the
      time needed to reach maximal satiation and total caloric intake was calculated
      after participants (20 normal weight, 20 obese) imbibed a standardized nutrient
      drink. In the second part gastric emptying of solids and liquids was evaluated
      using the (13)C-breath test (participants: 16 normal weight, 9 obese for gastric
      emptying of solids; 15 normal weight, 14 obese for gastric emptying of liquids).
      And in the third part, fasting and post-prandial plasma glucagon-like peptide-1
      (GLP-1), peptide tyrosine tyrosine (PYY) and ghrelin levels were measured after a
      standardized nutrient drink (participants: 20 normal weight, 20 obese). RESULTS:
      Our results show that, when compared to those of normal weight, obese
      participants reached maximal satiation sooner (P=0.006), their total intake of
      calories was higher (P=0.013), and their gastric emptying rates were delayed
      (P<0.001). Furthermore, their post-prandial increase in plasma GLP-1 and PYY was
      reduced, (P<0.001 for both), as was their ghrelin suppression (P=0.001).
      DISCUSSION: We conclude that, in obese subjects gastric emptying can be impaired
      with delayed interaction of nutrients with the intestine resulting in decreased
      GLP-1 and PYY secretion. This could imply that obese participants would require
      more calories before their maximal satiation is reached and they stop eating.

PMID- 24582674
TI  - Effects of inescapable versus escapable social stress in Syrian hamsters: the
      importance of stressor duration versus escapability.
AB  - Social avoidance is a common characteristic of many clinical psychopathologies
      and is often triggered by social stress. Our lab uses Syrian hamsters to model
      stress-induced social avoidance, and we have previously established that both
      inescapable and escapable social defeat result in increased social avoidance when
      compared with no-defeat controls. Our previous work suggested, however, that
      social avoidance was significantly greater after inescapable defeat. The goal of
      this study was to determine if this difference in behavior after the two types of
      defeat was due to experimental differences in the controllability (i.e.,
      escapability) of the defeat or simply to differences in the overall duration of
      the defeat. In Experiment 1, we used a yoked design to hold constant the duration
      of defeat between escapable and inescapable defeat conditions. This design
      resulted in only a very brief social defeat, yet when comparing defeated animals
      with no-defeat controls, a significant increase in social avoidance was still
      observed. In Experiment 2, we also used the yoked design, but the escape task was
      made more difficult to ensure a longer defeat experience. Again, we observed no
      effect of controllability. Together, these data suggest that the ability to
      escape a social stressor does not reduce the impact of the stressful experience.
      These results emphasize that social stressors need not be prolonged or
      uncontrollable to produce marked effects on subsequent behavior. 

PMID- 24582675
TI  - Prenatal stress decreases spatial learning and memory retrieval of the adult male
      offspring of rats.
AB  - INTRODUCTION: Early life or prenatal stress induces many lifelong, mostly
      cognitive, homeostatic alterations in the behavior of the offspring. PURPOSE: We
      investigated the effect of heterogeneous sequential stress (HSS) at three
      separate periods, before and during the first and second half of pregnancies on
      spatial learning and memory retrieval of adult male offspring. METHOD: HSS is
      composed of several stressors, each in a day, during nine consecutive days
      including; restraint, swimming, isolation, and water and food deprivation on
      Wistar rats. The offspring were studied in a Morris water maze (MWM) apparatus to
      explore the latency, distance, proximity and target to opposite area as measures
      of learning and memory. Serum corticosterone was measured as a criterion of
      stress application. RESULTS: HSS increased blood corticosterone in dams of PS2
      (Pregnancy Stress second half), and also in adult male offspring from BPS (Before
      Pregnancy Stress) and PS1 (Pregnancy Stress first half) groups. The weight of the
      offspring decreased in the PS1 and PS2 groups. While distance traveled and
      latency to locate the hidden platform were increased in BPS and PS1 acquisition
      trials, swimming speed was unchanged during the acquisition and retrieval tests.
      Moreover, time to platform location was increased in BPS and PS1 during retention
      tests. While control rats spent more time in the target quadrant, stressed
      animals spent a longer duration in the opposite quadrant. Furthermore, proximity
      measure was increased in all stress treated rats. CONCLUSION: It is concluded
      that prenatal stress, around the beginning of the pregnancy, increases
      corticosterone in adult male offspring, which might be the basis for spatial
      learning and memory retrieval deficits in this study.

PMID- 24582676
TI  - Salivary nerve growth factor response to stress related to resilience.
AB  - Salivary nerve growth factor (sNGF) has recently been shown to respond to
      psychosocial stress, but little is known about how individual differences in this
      neurotrophic marker relate to stress vulnerability vs. resilience. This study
      followed up on these initial findings by examining sNGF responses to
      interpersonal stress in relation to both well-being and state/trait factors that
      determine the way a person approaches and is impacted by stress. Young adults
      (n=40) gave 5 saliva samples over the course of a laboratory session that
      involved an interpersonal conflict stressor, and all samples were assayed for
      sNGF. Participants also completed self-report measures of global well-being,
      stress appraisals before and following the conflict, and agency. Greater sNGF
      reactivity to conflict related to stronger appraisals of coping ability and
      agency. Post-conflict sNGF recovery related to lower anticipatory stress
      appraisals, and to higher agency and well-being. These results support the idea
      that dynamic sNGF responses are adaptive. Implications for the potential role of
      the neurotrophic system in stress resilience are discussed. 

PMID- 24582677
TI  - Cisplatin induces neuronal activation and increases central AMPA and NMDA
      receptor subunit gene expression in mice.
AB  - Although rats and mice do not vomit, these species are widely studied as models
      of energy balance and sickness behavior. Previous work has shown that rats
      exhibit similar neuroanatomical activation of brain and visceral afferent
      pathways following cisplatin chemotherapy compared to vomiting species. However,
      the neural response to cisplatin in mice is understudied. Here, food intake, body
      weight, and central c-Fos immunofluorescence were analyzed in the hindbrains of
      male C57BL/6 mice following IP saline or cisplatin (5mg/kg, and 20mg/kg doses).
      As glutamate receptor signaling is classically linked to inhibitory feeding
      pathways in the rodent, gene expression of selected alpha-Amino-3-hydroxy-5
      methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-d-aspartic acid (NMDA)
      receptor subunits were assessed in the dorsal vagal complex (DVC), parabrachial
      nucleus (PBN), amygdala, and bed nucleus of the stria terminalis (BNST). Our
      results show dose-dependent reductions in food intake and body weight following
      cisplatin treatment, as well as increases in cisplatin-induced c-Fos in the PBN
      and throughout the DVC. Quantitative PCR analysis shows cisplatin-induced
      increases in NMDA receptor subunit expression, particularly NR2B, in the DVC,
      PBN, BNST, and amygdala. In addition, upregulation of AMPA receptor subunits
      (GluA1 and/or GluA2) were observed in all regions examined except the amygdala.
      Taken together, these results suggest similar neural pathways mediating cisplatin
      effects in mice compared to other well-studied species, which are likely mediated
      by central upregulation of AMPA and NMDA receptors. 

PMID- 24582678
TI  - Antidepressant effects of insulin in streptozotocin induced diabetic mice:
      Modulation of brain serotonin system.
AB  - Diabetes is a persistent metabolic disorder, which often leads to depression as a
      result of the impaired neurotransmitter function. Insulin is believed to have
      antidepressant effects in depression associated with diabetes; however, the
      mechanism underlying the postulated effect is poorly understood. In the present
      study, it is hypothesized that insulin mediates an antidepressant effect in
      streptozotocin (STZ) induced diabetes in mice through modulation of the serotonin
      system in the brain. Therefore, the current study investigated the antidepressant
      effect of insulin in STZ induced diabetes in mice and insulin mediated modulation
      in the brain serotonin system. In addition, the possible pathways that lead to
      altered serotonin levels as a result of insulin administration were examined.
      Experimentally, Swiss albino mice of either sex were rendered diabetic by a
      single intraperitoneal (i.p.) injection of STZ. After one week, diabetic mice
      received a single dose of either insulin or saline or escitalopram for 14days.
      Thereafter, behavioral studies were conducted to test the behavioral despair
      effects using forced swim test (FST) and tail suspension test (TST), followed by
      biochemical estimations of serotonin concentrations and monoamine oxidase (MAO)
      activity in the whole brain content. The results demonstrated that, STZ treated
      diabetic mice exhibited an increased duration of immobility in FST and TST as
      compared to non-diabetic mice, while insulin treatment significantly reversed the
      effect. Biochemical assays revealed that administration of insulin attenuated STZ
      treated diabetes induced neurochemical alterations as indicated by elevated
      serotonin levels and decreased MAO-A and MAO-B activities in the brain.
      Collectively, the data indicate that insulin exhibits antidepressant effects in
      depression associated with STZ induced diabetes in mice through the elevation of
      the brain serotonin levels. 

PMID- 24582679
TI  - Short and long-term energy intake patterns and their implications for human body
      weight regulation.
AB  - Adults consume millions of kilocalories over the course of a few years, but the
      typical weight gain amounts to only a few thousand kilocalories of stored energy.
      Furthermore, food intake is highly variable from day to day and yet body weight
      is remarkably stable. These facts have been used as evidence to support the
      hypothesis that human body weight is regulated by active control of food intake
      operating on both short and long time scales. Here, we demonstrate that active
      control of human food intake on short time scales is not required for body weight
      stability and that the current evidence for long term control of food intake is
      equivocal. To provide more data on this issue, we emphasize the urgent need for
      developing new methods for accurately measuring energy intake changes over long
      time scales. We propose that repeated body weight measurements can be used along
      with mathematical modeling to calculate long-term changes in energy intake and
      thereby quantify adherence to a diet intervention and provide dynamic feedback to
      individuals that seek to control their body weight. 

PMID- 24582680
TI  - Endobronchial mass and ipsilateral pleural effusion as presenting features of
      sarcoidosis.

PMID- 24582681
TI  - Hepatoprotective effects of fermented field water-dropwort (Oenanthe javanica)
      extract and its major constituents.
AB  - Dropwort (Oenanthe javanica) has been used for many years for the treatment of
      inflammatory conditions, including hepatitis. We investigated the protective
      effects of fermented field water-dropwort extract (FDE) on tert-butyl
      hydroperoxide (t-BHP)-induced hepatotoxicity in HepG2 cells and carbon
      tetrachloride (CCl4)-induced liver damage in rats. Pretreatment with FDE prior to
      the t-BHP treatment of HepG2 cells inhibited cell death and lactate dehydrogenase
      (LDH) leakage in a dose-dependent manner. In addition FDE significantly prevented
      the increase of hepatic enzyme markers (ALT, AST) in vivo. Moreover, FDE
      administration for 7 days significantly affected CYP2E1, CYP4A2, and PPARgamma
      gene expressions. CYP2E1 and CYP4A2 gene expression in the liver, increased 2 and
      22-fold by CCl4 administration, respectively, was attenuated to normal levels by
      pretreatment with FDE. PPARgamma gene expression, completely blocked by CCl4
      treatment, was increased by FDE pretreatment compared to normal control group.
      Histopathological examination of the livers also revealed that FDE reduced the
      incidence of liver lesions. Caffeic acid and chlorogenic acid were identified as
      major constituents of FDE. These results demonstrate the protective effects of
      FDE against hepatocytotoxicity induced by CCl4 and t-BHP in rats and HepG2 cells,
      thus indicating the potential of FDE as a therapeutic for acute liver diseases.

PMID- 24582683
TI  - Safety and mutagenicity evaluation of red mold dioscorea fermented from Monascus
      purpureus NTU 568.
AB  - Monascus-fermented products, including red mold rice and red mold dioscorea, have
      been developed as functional foods with many health benefits. We performed safety
      and mutagenic evaluations on red mold dioscorea powder (RMDP) fermented from
      Monascus purpureus NTU 568. The results of Ames test using Salmonella typhimurium
      strains TA97a, TA98, TA100, TA102, and TA1535 showed that RMDP (?5 mg/plate) was
      not mutagenic. The mammalian chromosomal aberration test showed that the number
      of Chinese hamster ovary cells with abnormal chromosomes was <3% after RMDP
      treatment (maximum concentration: 5 mg/mL). Imprinting control region mice were
      used to estimate the genotoxicity of RMDP. Compared with the control, high-dose
      RMDP administration (2000 mg/kg) did not show significant differences in the
      number of reticulocytes or the occurrence of micronucleated reticulocytes. A 28
      day oral toxicity assay in Sprague-Dawley rats was performed to investigate the
      no observed adverse effect level of RMDP. Compared with the control, high-dose
      RMDP administration (2000 mg/kg) caused no toxicological responses such as
      mortality, variation in body weight, or toxicopathologic lesions. Thus, RMDP from
      M. purpureus NTU 568 shows no significant mutagenic or toxic effects.

PMID- 24582682
TI  - Reproductive toxicity in rats with crystal nephropathy following high doses of
      oral melamine or cyanuric acid.
AB  - The industrial chemical melamine was used in 2007 and 2008 to raise the apparent
      protein content in pet feed and watered down milk, respectively. Because humans
      may be exposed to melamine via several different routes into the human diet as
      well as deliberate contamination, this study was designed to characterize the
      effect of high dose melamine or cyanuric acid oral exposure on the pregnant
      animal and developing fetus, including placental transfer. Clear rectangular
      crystals formed following a single triazine exposure which is a different
      morphology from the golden spherulites caused by combined exposure or the calculi
      formed when melamine combines with endogenous uric acid. Crystal nephropathy,
      regardless of cause, induces renal failure which in turn has reproductive
      sequelae. Specifically, melamine alone-treated dams had increased numbers of
      early and late fetal deaths compared to controls or cyanuric acid-treated dams.
      As melamine was found in the amniotic fluid, this study confirms transfer of
      melamine from mammalian mother to fetus and our study provides evidence that
      cyanuric acid also appears in the amniotic fluid if mothers are exposed to high
      doses. 

PMID- 24582684
TI  - Nothing's perfect: the art of defining HLA-specific antibodies.
AB  - The advent of solid phase assays and in particular the single antigen bead (SAB)
      assay, on the Luminex platform has led to previously unheralded levels of HLA
      specific antibody characterisation. However, it soon became apparent that the
      detection of antibodies detected by these assays was less than perfect and that
      not all antibodies determined could be considered clinically relevant. Thus, the
      major challenges currently faced by HLA laboratories are to interpret the complex
      data provided by these assays and use this to devise a safe and practical
      algorithm for the definition of a clinically relevant HLA-specific antibody.
      Taking into consideration recent evidence and scientific opinion in this area we
      aim here to put forward the viewpoint of our laboratory in how best to manage the
      tricky problem of defining HLA-specific antibodies. By taking a balanced approach
      which is less reliant upon a single technique we propose that the aim should be
      to define antibodies to a level that does not discriminate against the highly
      sensitised patient, but also maintains clinical safety and efficacy. Knowing that
      not all of the antibodies detected by SAB are clinically relevant should lead to
      giving greater opportunity for patients with these antibodies having a crossmatch
      performed. In the future, more emphasis should be given to epitopes when
      interpreting the results of these assays. 

PMID- 24582685
TI  - Heritability of arterial stiffness and carotid intima-media thickness: an Italian
      twin study.
AB  - BACKGROUND AND AIMS: Carotid intima-media thickness (IMT) and arterial stiffness
      parameters, including aortic augmentation index (AIx) and pulse wave velocity
      (PWV), are independent predictors of stroke and cardiovascular disease. Genetic
      effects on these traits were never explored in a Mediterranean country. The
      present study aims to quantify the contribution of genes, environment and age to
      carotid IMT and aortic Aix and PWV. METHODS AND RESULTS: The twin design was
      used. A total of 348 adult twins from the Italian Twin Register underwent
      measurements of carotid IMT and aortic PWV and AIx in three university hospitals
      located in Rome, Padua and Perugia. Carotid IMT was measured by B-mode
      ultrasound, aortic PWV and AIx by Arteriograph. Genetic modelling was performed
      to decompose total variance of traits into genetic, shared and unshared
      environmental and age components. For each phenotype, the best-fitting model
      included additive genetic, unshared environmental and age effects. For IMT,
      heritability was 0.32 (95% confidence interval (CI): 0.25-0.38), unshared
      environmental component was 0.25 (0.18-0.32) and age contribution was 0.44 (0.39
      0.49). For AIx and PWV, heritabilities were 0.42 (0.29-0.55) and 0.49 (0.35
      0.62), unshared environmental components were 0.31 (0.22-0.44) and 0.37 (0.26
      0.51) and age contributions were 0.27 (0.16-0.39) and 0.14 (0.06-0.24),
      respectively. CONCLUSION: This study shows substantial genetic and unshared
      environmental influences on carotid intima-media thickness and arterial stiffness
      and confirms the relevant role of age in the aetiology of these traits. Further
      support is provided for prevention and health promotion strategies based on
      modifiable factors.

PMID- 24582686
TI  - The ideal blood pressure target to prevent cardiovascular disease in type 2
      diabetes: a neutral viewpoint.
AB  - Type 2 diabetes mellitus (T2DM) and essential hypertension are often associated,
      and retrospective data analyses suggest an association between lower blood
      pressure (BP) values and lower cardiovascular (CV) risk in patients with T2DM.
      However, the most recent intervention trials fail to demonstrate a further CV
      risk reduction, for BP levels <130/80 mm Hg, when compared to levels <140/90 mm
      Hg. Moreover, a J-shaped, rather than a linear, relationship of BP reduction with
      incident CV events has been strongly suggested. We here debate the main available
      evidences for and against the concept of 'the lower the better', in the light of
      the main intervention trials and meta-analyses, with a particular emphasis on the
      targets to be pursued in elderly patients. Finally, the most recent guidelines of
      the scientific societies are critically discussed.

PMID- 24582687
TI  - Acute chlorine gas exposure produces transient inflammation and a progressive
      alteration in surfactant composition with accompanying mechanical dysfunction.
AB  - Acute Cl2 exposure following industrial accidents or military/terrorist activity
      causes pulmonary injury and severe acute respiratory distress. Prior studies
      suggest that antioxidant depletion is important in producing dysfunction, however
      a pathophysiologic mechanism has not been elucidated. We propose that acute Cl2
      inhalation leads to oxidative modification of lung lining fluid, producing
      surfactant inactivation, inflammation and mechanical respiratory dysfunction at
      the organ level. C57BL/6J mice underwent whole-body exposure to an effective
      60ppm-hour Cl2 dose, and were euthanized 3, 24 and 48h later. Whereas pulmonary
      architecture and endothelial barrier function were preserved, transient
      neutrophilia, peaking at 24h, was noted. Increased expression of ARG1, CCL2,
      RETLNA, IL-1b, and PTGS2 genes was observed in bronchoalveolar lavage (BAL) cells
      with peak change in all genes at 24h. Cl2 exposure had no effect on NOS2 mRNA or
      iNOS protein expression, nor on BAL NO3(-) or NO2(-). Expression of the
      alternative macrophage activation markers, Relm-alpha and mannose receptor was
      increased in alveolar macrophages and pulmonary epithelium. Capillary
      surfactometry demonstrated impaired surfactant function, and altered BAL
      phospholipid and surfactant protein content following exposure. Organ level
      respiratory function was assessed by forced oscillation technique at 5 end
      expiratory pressures. Cl2 exposure had no significant effect on either airway or
      tissue resistance. Pulmonary elastance was elevated with time following exposure
      and demonstrated PEEP refractory derecruitment at 48h, despite waning
      inflammation. These data support a role for surfactant inactivation as a
      physiologic mechanism underlying respiratory dysfunction following Cl2
      inhalation. 

PMID- 24582688
TI  - Reactive oxygen species contribute to arsenic-induced EZH2 phosphorylation in
      human bronchial epithelial cells and lung cancer cells.
AB  - Our previous studies suggested that arsenic is able to induce serine 21
      phosphorylation of the EZH2 protein through activation of JNK, STAT3, and Akt
      signaling pathways in the bronchial epithelial cell line, BEAS-2B. In the present
      report, we further demonstrated that reactive oxygen species (ROS) were involved
      in the arsenic-induced protein kinase activation that leads to EZH2
      phosphorylation. Several lines of evidence supported this notion. First, the
      pretreatment of the cells with N-acetyl-l-cysteine (NAC), a potent antioxidant,
      abolishes arsenic-induced EZH2 phosphorylation along with the inhibition of JNK,
      STAT3, and Akt. Second, H2O2, the most important form of ROS in the cells in
      response to extracellular stress signals, can induce phosphorylation of the EZH2
      protein and the activation of JNK, STAT3, and Akt. By ectopic expression of the
      myc-tagged EZH2, we additionally identified direct interaction and
      phosphorylation of the EZH2 protein by Akt in response to arsenic and H2O2.
      Furthermore, both arsenic and H2O2 were able to induce the translocation of
      ectopically expressed or endogenous EZH2 from nucleus to cytoplasm. In summary,
      the data presented in this report indicate that oxidative stress due to ROS
      generation plays an important role in the arsenic-induced EZH2 phosphorylation.

PMID- 24582689
TI  - TNF/TNFR1 pathway and endoplasmic reticulum stress are involved in ofloxacin
      induced apoptosis of juvenile canine chondrocytes.
AB  - BACKGROUND AND PURPOSE: Quinolones cause obvious cartilaginous lesions in
      juvenile animals by chondrocyte apoptosis, which results in the restriction of
      their use in pediatric and adolescent patients. Studies showed that chondrocytes
      can be induced to produce TNFalpha, and the cisternae of the endoplasmic
      reticulum in quinolone-treated chondrocytes become dilated. We investigated
      whether TNF/TNFR1 pathway and endoplasmic reticulum stress (ERs) are involved in
      ofloxacin (a typical quinolone)-induced apoptosis of juvenile canine
      chondrocytes. EXPERIMENTAL APPROACH: Canine juvenile chondrocytes were treated
      with ofloxacin. Cell survival and apoptosis rates were determined with MTT method
      and flow cytometry, respectively. The gene expression levels of the related
      signaling molecules (TNFalpha, TNFR1, TRADD, FADD and caspase-8) in death
      receptor pathways and main apoptosis-related molecules (calpain, caspase-12,
      GADD153 and GRP78) in ERs were measured by qRT-PCR. The gene expression of TNFR1
      was suppressed with its siRNA. The protein levels of TNFalpha, TNFR1 and caspase
      12 were assayed using Western blotting. KEY RESULTS: The survival rates decreased
      while apoptosis rates increased after the chondrocytes were treated with
      ofloxacin. The mRNA levels of the measured apoptosis-related molecules in death
      receptor pathways and ERs, and the protein levels of TNFalpha, TNFR1 and caspase
      12 increased after the chondrocytes were exposed to ofloxacin. The downregulated
      mRNA expressions of TNFR1, Caspase-8 and TRADD, and the decreased apoptosis rates
      of the ofloxacin-treated chondrocytes occurred after TNFR1-siRNA interference.
      CONCLUSIONS AND IMPLICATIONS: Ofloxacin-induced chondrocyte apoptosis in a time-
      and concentration-dependent fashion. TNF/TNFR1 pathway and ERs are involved in
      ofloxacin-induced apoptosis of juvenile canine chondrocytes in the early stage.

PMID- 24582690
TI  - A metabonomic evaluation of the monocrotaline-induced sinusoidal obstruction
      syndrome (SOS) in rats.
AB  - The main curative treatment of colorectal cancer remains the surgery. However,
      when metastases are suspected, surgery is followed by a preventive chemotherapy
      using oxaliplatin which, unfortunately, may cause liver sinusoidal obstruction
      syndrome (SOS). Such hepatic damage is barely detected during or after
      chemotherapy due to a lack of effective diagnostic procedures, but liver biopsy.
      The primary objective of the present study was to identify potential early
      diagnosis biomarkers of SOS using a metabonomic approach. SOS was induced in rats
      by monocrotaline, a prototypical toxic substance. (1)H NMR spectroscopy analysis
      of urine samples collected from rats treated with monocrotaline showed
      significant metabolic changes as compared to controls. During a first phase,
      cellular protective mechanisms such as an increased synthesis of GSH (reduced
      taurine) and the recruitment of cell osmolytes in the liver (betaine) were seen.
      In the second phase, the disturbance of the urea cycle (increased ornithine and
      urea reduction) leading to the depletion of NO, the alteration in the GSH
      synthesis (increased creatine and GSH precursors (glutamate, dimethylglycine and
      sarcosine)), and the liver necrosis (decrease taurine and increase creatine) all
      indicate the development of SOS. 

PMID- 24582691
TI  - Augmented atherogenesis in ApoE-null mice co-exposed to polychlorinated biphenyls
      and 2,3,7,8-tetrachlorodibenzo-p-dioxin.
AB  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and polychlorinated biphenyls (PCBs)
      are persistent organic pollutants found as complex mixtures in the environment
      throughout the world. Therefore, humans are ubiquitously and simultaneously
      exposed to TCDD and PCBs. TCDD and PCBs alone have been linked to
      atherosclerosis. However, the effects of interactions or synergism between TCDD
      and PCBs on atherogenesis are unknown. We investigated the possible enhanced
      atherogenesis by co-exposure to TCDD and PCBs and the potential mechanism(s)
      involved in this enhancement. Male ApoE(-/-) mice were exposed to TCDD (15
      MUg/kg) and Aroclor1254 (55 mg/kg, a representative mixture of PCBs) alone or in
      combination by intraperitoneal injection four times over six weeks of duration.
      Our results showed that mice exposed to TCDD alone, but not Aroclor1254 alone,
      developed atherosclerotic lesions. Moreover, we found that atherosclerotic
      disease was exacerbated to the greatest extent in mice co-exposed to TCDD and
      Aroclor1254. The enhanced lesions correlated with several pro-atherogenic
      changes, including a marked increase in the accumulation of the platelet-derived
      chemokine PF4, and the expression of the proinflammatory cytokine MCP-1 and the
      critical immunity gene-RIG-I. Our data demonstrated that co-exposure to TCDD and
      Aroclor1254 markedly enhanced atherogenesis in ApoE(-/-) mice. Significantly, our
      observations suggest that combined exposure to TCDD and PCBs may be a greater
      cardiovascular health risk than previously anticipated from individual studies.

PMID- 24582692
TI  - The teaching of posterior resin composites: planning for the future based on 25
      years of research.
AB  - OBJECTIVES: The restoration of posterior teeth affected by caries, trauma or wear
      remains one of the commonest procedures in the practice of dentistry. Over the
      past 20 years the first author and latterly the second author have led a series
      of surveys around the world to capture information on the teaching of posterior
      resin composites. The aim of this paper is to identify trends, reflect on the
      findings and make recommendations for the further development of this important
      aspect of the curriculum for primary dental qualifications. METHODS: Surveys on
      the teaching of posterior resin composites were completed in 1986, 1997-99, 2004
      05 and 2007-2009. The findings from these surveys were reviewed and drawn
      together to allow historical and contemporary international trends to be
      identified. Recommendations for further developments in the teaching of posterior
      resin composites were formulated from the cumulated data and trends identified.
      RESULTS: Information was available from a total of 679 survey returns. Increased
      teaching of posterior resin composites has been observed over the period of the
      surveys: while 90% of dental school curricula did not include any didactic
      teaching of posterior resin composites in the mid-1980s, this dropped to 4% or
      less in the late 1990s, and to 0% in the early 2000s. In the late 2000s, however,
      21% of dental schools still did not teach the placement of resin composites in
      three-surface cavities in permanent molar teeth. Areas of confusion were reported
      in the teaching of certain aspects of cavity design, notably the use of bevels,
      and in the protection of operatively exposed dentine. CONCLUSIONS: While there
      has been steady growth in, and trends towards evidence-based teaching of
      posterior resin composites in dental schools around the world over the last 20-25
      years, there is a need for further developments and harmonisation in this
      important aspect of curricula for primary dental qualifications. This need is now
      pressing, subsequent to the signing of the Minamata Convention. It is recommended
      that all new graduates, from no later than 2020, should have the knowledge,
      skills, competences and confidence to effectively restore damaged and diseased
      posterior teeth with state-of-the-art resin composite systems.

PMID- 24582694
TI  - Effect of cardiac rehabilitation on left atrial functions in patients with acute
      myocardial infarction.
AB  - BACKGROUND: The objective of this study was to analyze the effects of cardiac
      rehabilitation (CR) on the atrial function of patients with acute myocardial
      infarction (AMI) who had been successfully revascularized through percutaneous
      coronary intervention (PCI). METHODS: Forty-two AMI patients having undergone CR
      were enrolled in this observational study. Assessments were performed before and
      after 6 weeks of CR. Left atrial strain analysis was carried out by two
      dimensional speckle tracking echocardiography. Left ventricular ejection fraction
      (LVEF) was measured by the biplane Simpson's method. Pulsed-wave Doppler at the
      tip of mitral valve leaflets enabled us to measure early (E) and late (A)
      diastolic filling velocities, deceleration time (DT) of early filling velocity
      and isovolumic relaxation time (IVRT). Left ventricle tissue velocity was
      measured by tissue Doppler imaging of the lateral mitral annulus (e') and E/e'
      was subsequently calculated. Ratio of E/e' to left atrium (LA) peak strain was
      used to estimate LA stiffness. RESULTS: Following CR, LVEF (P=0.010), LA strain
      (P<0.001) and LA stiffness (P=0.013) all showed improvement, while other
      parameters remained unchanged. CONCLUSION: Post-AMI cardiac rehabilitation and
      revascularization by PCI might have favourable effects on LA function.

PMID- 24582693
TI  - Modulation of Atg5 expression by globular adiponectin contributes to autophagy
      flux and suppression of ethanol-induced cell death in liver cells.
AB  - Globular adiponectin (gAcrp) protects liver cells from ethanol-induced apoptosis
      via induction of autophagy. However, the underlying mechanisms are unknown. The
      present study aims to investigate the potential role of autophagy-related protein
      5 (Atg5), an essential Atg for the elongation of autophagosomes, in suppression
      of ethanol-induced cytotoxicity by gAcrp. Here, we demonstrated that suppression
      of Atg5 expression by ethanol was restored by pretreatment with gAcrp both in
      primary rat hepatocytes and human hepatoma cell line (HepG2). Moreover, ethanol
      induced accumulation of p62 (sequestosome1), a marker of autophagic flux, was
      restored by gAcrp treatment, implying that gAcrp modulates autophagic flux in
      liver cells. Further, Atg5 silencing prevented p62 degradation by gAcrp,
      suggesting that Atg5 plays a critical role in induction of autophagic flux by
      gAcrp. Interestingly, gene silencing of Atg5 by siRNA abrogated restoration of
      autophagosome formation by gAcrp in ethanol-treated cells. Finally, protection of
      liver cells by gAcrp from ethanol-induced apoptosis was also significantly
      attenuated by knocking-down of Atg5 expression, suggesting an important role of
      Atg5 in autophagy induction and cellular apoptosis modulated by gAcrp. Taken
      together, our data demonstrated that Atg5 expression, at least in part, is
      implicated in gAcrp-induced autophagy and subsequent anti-apoptotic effects in
      ethanol-treated liver cells. 

PMID- 24582695
TI  - Fabry disease: a new approach for the screening of females in high-risk groups.
AB  - OBJECTIVE: Fabry disease (FD) is a rare X-linked inborn error of metabolism
      caused by deficient activity of lysosomal alpha-galactosidase A (alpha-GAL). Due
      to random X inactivation, alpha-GAL activity in heterozygous females ranges from
      very low to overlapping normal values. Determining this specific range and
      altering assays cutoffs could become a valuable tool for minimizing the need in
      DNA sequencing for screening of all potential carriers. Therefore, the aim of
      this study was to establish the range of enzyme in dried blood spots (DBS),
      plasma and leukocytes that suggests carrier status for FD. DESIGN AND METHODS:
      alpha-GAL gene was sequenced in 453 women with clinical suspicion and/or positive
      family history of FD. This data was compared to the alpha-GAL activity measured
      in DBS (dried blood spots) and/or plasma and/or leukocytes. RESULTS: About 12% of
      the samples had pathogenic mutations (c.30_32delG, c.718_719delAA, p.R118C,
      p.S126G, p.Y152X, p.A156D, p.C202Y, p.N215S, p.P259R, p.D264Y, p.V269M, p.R342Q
      and p.R356W). When compared to genotype, DBS was the least reliable biochemical
      test for screening, with very low specificity. Plasma and leukocyte activities
      presented high AUC in ROC curve analysis, both over 84%. When cutoffs were
      altered to identify all carriers, leukocyte specificity was higher than that of
      plasma (35.2% and 27.6%, respectively). Moderated correlation and agreement
      coefficients were found between them, which reinforces the need for using both
      data combined. CONCLUSION: A combined approach involving plasma and leukocyte
      alpha-GAL activities, with distinct cutoffs for men and women, could represent a
      more accurate, faster and less expensive tool to screen women for FD in high-risk
      groups in middle- and low-income countries.

PMID- 24582696
TI  - Novel insights into the pathophysiology of different forms of stress testing.
AB  - BACKGROUND: The impact of different forms of cardiac stress testing (exercise
      versus pharmacological stress testing) on cardiac wall stress and myocardial
      ischemia is incompletely understood. METHODS: In a prospective study, 331
      consecutive patients with suspected myocardial ischemia referred for nuclear
      perfusion imaging were enrolled: 266 underwent exercise (bicycle) stress testing
      and 65 adenosine stress testing. Levels of B-type natriuretic peptide (BNP)
      measured before and 1 min after stress testing, ischemic ECG changes, and typical
      angina symptoms were used to compare the 2 testing modalities. RESULTS: Cardiac
      wall stress as quantified by changes in BNP levels significantly increased in the
      exercise stress group, but not in the adenosine group (increase in BNP levels 22
      pg/ml (IQR 6-46) versus -3 pg/ml (IQR -3 to 28); p<0.001). In the bicycle
      exercise stress group, patients with reversible defects on nuclear perfusion
      imaging more often had angina symptoms (25% vs. 9%, p=0.0001) and ischemic ECG
      changes (33% vs. 12%, p=0.0001) during the stress test, and a greater increase in
      BNP levels (28 (IQR 11-58) versus 16 (IQR 3-34) pg/ml, p=0.001) compared to those
      without reversible defects. Those differences between patients with and without
      reversible defects were not observed with the adenosine protocol (p-values all
      >0.05). CONCLUSION: Exercise stress testing but not adenosine stress results in
      an increase of cardiac wall stress, angina symptoms and ECG changes. The absence
      of these surrogates of myocardial ischemia suggests that adenosine stress does
      not induce acute myocardial ischemia, but rather displays relative perfusion
      differences.

PMID- 24582697
TI  - Characteristics of unexpected protein bands in multiple myeloma patients after
      autologous stem cell transplantation.
AB  - OBJECTIVES: The aim of this study is to investigate the characteristics of
      unexpected protein bands (UPBs) in patients with multiple myeloma (MM). DESIGN
      AND METHODS: Individuals diagnosed with MM (n=193) were enrolled. Their medical
      records and IFE patterns were reviewed. RESULTS: Of the patients that underwent
      ASCT, 54% developed UPBs. The median time for UPB appearance and duration was 1.8
      and 5.7months, respectively. IFE revealed 74.1% of UPBs to be of the
      immunoglobulin G type and 72.2% to be of the kappa-type. At UPB appearance, 42.6%
      of patients were defined as sCR or CR, and 50.0% of the patients satisfying the
      CR criteria had an abnormal FLC ratio. Of the patients who developed UPBs, five
      relapsed. Among these, four patients showed disappearance of the previous IFE
      oligoclonality and reappearance of the original paraprotein at relapse.
      CONCLUSIONS: Close follow-up of UPBs is critical for evaluating MM therapeutic
      response and disease progression. The presence of monoclonal bands may indicate
      relapse of disease, but in the vast majority of cases with UPBs, it does not;
      instead, it most likely represents a transient phenomenon caused by the immune
      response.

PMID- 24582698
TI  - The differential metabolite profiles of acute lymphoblastic leukaemic patients
      treated with 6-mercaptopurine using untargeted metabolomics approach.
AB  - BACKGROUND: Acute lymphoblastic leukaemia (ALL) has posed challenges to the
      clinician due to variable patients' responses and late diagnosis. With the
      advance in metabolomics, early detection and personalised treatment are possible.
      METHODS: Metabolomic profile of 21 ALL patients treated with 6-mercaptopurine and
      10 healthy volunteers were analysed using liquid chromatography/mass spectrometry
      quadrupole-time of flight (LC/MS Q-TOF). Principal components analysis (PCA),
      recursive analysis, clustering and pathway analysis were performed using
      MassHunter Qualitative and Mass Profiler Professional (MPP) software. RESULTS:
      Several metabolites were found to be expressed differently in patients treated
      with 6-mercaptopurine. Interestingly, 13 metabolites were significantly
      differently expressed [p-value <0.01 (unpaired t-test) and 2-fold change] in 19%
      of the patients who had relapses in their treatment. Down-regulated metabolites
      in relapsed patients were 1-tetrahexanoyl-2-(8-[3]-ladderane-octanyl)-sn-GPEtn,
      GPEtn (18:1(9Z)/0:0), GPCho(O-6:0/O-6:0), GPCho(O-2:0/O-1:0), methyl 8-[2-(2
      formyl-vinyl)-3-hydroxy-5-oxo-cyclopentyl]-octanoate and plasma free amino acids
      (PFAA). Characterizing the subjects according to their ITPA 94C>A genotypes
      reveal differential expression of metabolites. CONCLUSIONS: Our research
      contributes to identification of metabolites that could be used to monitor
      disease progress of patients and allow targeted therapy for ALL at different
      stages, especially in preventing complication of relapse.

PMID- 24582699
TI  - The global epidemiology of anabolic-androgenic steroid use: a meta-analysis and
      meta-regression analysis.
AB  - PURPOSE: To estimate the global lifetime prevalence rate of anabolic-androgenic
      steroid (AAS) use and investigate moderators of the prevalence rate. METHODS: A
      meta-analysis and meta-regression analysis was performed using studies gathered
      from searches in PsycINFO, PubMed, ISI Web of Science, and Google Scholar among
      others. Included were 187 studies that provided original data on 271 lifetime
      prevalence rates. Studies were coded for publication year, region, sample type,
      age range, sample size, assessment method, and sampling method. Heterogeneity was
      assessed by the I(2) index and the Q-statistic. Random effect-size modeling was
      used. Subgroup comparisons were conducted using Bonferroni correction. RESULTS:
      The global lifetime prevalence rate obtained was 3.3% (95% confidence interval
      [CI], 2.8-3.8; I(2) = 99.7, P < .001). The prevalence rate for males, 6.4% (95%
      CI, 5.3-7.7, I(2) = 99.2, P < .001), was significantly higher (Qbet = 100.1, P <
      .001) than the rate for females, 1.6% (95% CI, 1.3-1.9, I(2) = 96.8, P < .001).
      Sample type (athletes), assessment method (interviews only and interviews and
      questionnaires), sampling method, and male sample percentage were significant
      predictors of AAS use prevalence. There was no indication of publication bias.
      CONCLUSION: Nonmedical AAS use is a serious widespread public health problem.

PMID- 24582701
TI  - Pelvic ischemia and quality of life scores after interventional occlusion of the
      hypogastric artery in patients undergoing endovascular aortic aneurysm repair.
AB  - OBJECTIVE: The aim of this study was to analyze the pelvic ischemic complications
      and their impact on quality of life after interventional occlusion of the
      hypogastric artery (IOHA) in patients undergoing endovascular aortic aneurysm
      repair (EVAR). METHODS: Between January 2004 and April 2012, 638 consecutive
      patients with aortoiliac aneurysm treated by EVAR were prospectively registered
      in two teaching hospitals. We identified all EVAR patients who underwent IOHA.
      Demographic, clinical, and radiologic data were extracted from electronic
      databases and patient records as requested. All patients who survived the
      postoperative period took part in a quality of life survey, the Walking
      Impairment Questionnaire (WIQ), which included four items: pain, distance,
      walking speed, and stair climbing. Outcome measures included the 30-day rate of
      pelvic ischemic complications, the buttock claudication (BC) rate at 30 days and
      during follow-up, and the comparative WIQ scores between patients with persistent
      BC, those with regressive BC, and those who never had BC after the IOHA
      procedure. RESULTS: A total of 71 patients (97% men; mean age, 76 years +/- 7.69)
      required 75 IOHA procedures. These were deemed proximal in 44 cases and distal in
      31, with use of coil embolization in 64%, Amplatzer plug in 24%, or a combination
      of coils and plugs in 12%. The technical success rate was 100%. Two patients
      (2.8%) experienced fatal acute pelvic ischemic complications in the postoperative
      period after EVAR. Another patient died of iliac rupture during EVAR, leading to
      an operative mortality rate of 4.3%. Eighteen patients (25.3%) suffered BC, among
      whom 11 cases resolved at a median follow-up of 42 months. Young age (odds ratio,
      0.92; 95% confidence interval, 0.85-0.99; P = .03) and distal IOHA (odds ratio,
      3.5; 95% confidence interval, 1.01-11.51; P = .04) were independent predictors of
      BC occurrence. The actuarial rate of persistent BC was 85% at 18 months. The WIQ
      scores were lower for patients with persistent BC (median score, 35.04;
      interquartile range, 16.36; P = .001) compared with patients with regressive BC
      (median score, 76.5; interquartile range, 36.66; P = .02) or those who never
      experienced BC after the IOHA procedure (median score, 65.34; interquartile
      range, 10.94; P < .0003). CONCLUSIONS: Pelvic ischemia associated with IOHA may
      be severe and lead to fatality after EVAR. Our data show that BC may lead to
      severe quality of life impairment when it does not regress during follow-up.

PMID- 24582700
TI  - Vitamin D deficiency is associated with mortality and adverse vascular access
      outcomes in patients with end-stage renal disease.
AB  - BACKGROUND: Plasma 25 hydroxycholecalciferol (vitamin D) deficiency has been
      associated with adverse cardiovascular outcomes in epidemiologic studies. Chronic
      kidney disease is associated with loss of 1alpha-hydroxylase and consequently
      vitamin D deficiency. We hypothesized that vitamin D deficiency was associated
      with increased mortality and increased vascular access failure in patients
      undergoing permanent vascular access for end-stage renal disease. METHODS: This
      retrospective cohort study analyzed 128 patients undergoing permanent vascular
      access surgery between 2003 and 2012 for whom concurrent plasma vitamin D levels
      were also available. Levels were considered deficient at <20 ng/mL. Multivariable
      analysis was used to determine the association between vitamin D and mortality
      and vascular access outcomes. RESULTS: The mean age was 66.7 years, 96.8% were
      male, 32.0% were African American, and 60.9% had diabetes mellitus. In the entire
      cohort, 55.5% were vitamin D-deficient, despite similar rates of repletion among
      the vitamin D-deficient and nondeficient groups. During a median follow-up of
      2.73 years, there were 40 deaths (31%). Vitamin D-deficient patients tended to be
      younger (P = .01) and to have higher total cholesterol (P = .001) and lower
      albumin (P = .017) and calcium (P = .007) levels. Despite their younger age,
      mortality was significantly higher (P = .026) and vascular access failure was
      increased (P = .008) in the vitamin D-deficient group. Multivariate logistic
      regression analysis found vitamin D deficiency (odds ratio [OR], 3.64; 95%
      confidence interval [CI], 1.12-11.79; P = .031), hemodialysis through a central
      catheter (OR, 3.08; 95% CI, 1.04-9.12; P = .042), coronary artery disease (OR,
      3.08; 95% CI, 1.06-8.94; P = .039), increased age (OR, 1.09; 95% CI, 1.03-1.15; P
      = .001), and albumin (OR, 0.27; 95% CI, 0.09-0.83; P = .023) remained independent
      predictors of mortality. Vitamin D deficiency (hazard ratio [HR], 2.34; 95% CI,
      1.17-4.71; P = .02), a synthetic graft (HR, 3.50; 95% CI, 1.38-8.89; P = .009),
      and hyperlipidemia (HR, 0.42; 95% CI, 0.22-0.81; P = .01) were independent
      predictors of vascular access failure in a Cox proportional hazard model.
      CONCLUSIONS: Vitamin D deficiency is highly prevalent in patients undergoing
      vascular access procedures. Patients who are deficient in vitamin D have worse
      survival and worse vascular access outcomes. Further study is warranted to assess
      whether aggressive vitamin D repletion will improve outcomes in this population.

PMID- 24582702
TI  - Aromatase is required for female abdominal aortic aneurysm protection.
AB  - OBJECTIVE: The protective effects of female gender on the development of
      abdominal aortic aneurysms (AAAs) have been attributed to anti-inflammatory
      effects of estrogen. Estrogen synthesis is dependent on the enzyme aromatase,
      which is located both centrally in the ovaries and peripherally in adipose
      tissue, bone, and vascular smooth muscle cells. It is hypothesized that deletion
      of aromatase in both ovarian and peripheral tissues would diminish the protective
      effect of female gender and would be associated with increased aortic diameter in
      female mice. METHODS: Male and female 8- to 10-week-old mice with aromatase (wild
      type: WT) and without aromatase (ArKO) underwent elastase aortic perfusion with
      aortic harvest 14 days following. For the contribution of central and peripheral
      estrogen conversion to be evaluated, female WT mice were compared with female WT
      and ArKO mice that had undergone ovariectomy (ovx) at 6 weeks followed by
      elastase perfusion at 8 to 10 weeks. At aortic harvest, maximal aortic dilation
      was measured and samples were collected for immunohistochemistry and protein
      analysis. Serum was collected for serum estradiol concentrations. Groups were
      compared with analysis of variance. Human and mouse AAA cross sections were
      analyzed with confocal immunohistochemistry for aromatase, smooth muscle markers,
      and macrophage markers. RESULTS: Female WT mice had significant reduction in
      aortic dilation compared with male WT mice (F WT, 51.5% +/- 15.1% vs M WT, 78.7%
      +/- 14.9%; P < .005). The protective effects of female gender were completely
      eliminated with deletion of aromatase (F ArKO, 82.6% +/- 13.8%; P < .05 vs F WT).
      Ovariectomy increased aortic dilation in WT mice (F WT ovx, 70.6% +/- 11.7%; P <
      .05 vs F WT). Aromatase deletion with ovariectomy further increased aortic
      dilation compared with WT ovx mice (F ArKO ovx, 87.3% +/- 14.7%, P < .001 vs F WT
      and P < .05 vs F WT ovx). Accordingly, female ArKO ovx mice had significantly
      higher levels of the proinflammatory cytokines monocyte chemoattractant protein 1
      and interleukin-1beta and were associated with increased macrophage staining and
      decreased elastin staining. Regarding serum hormone levels, decreasing estradiol
      levels correlated with increasing aortic diameter (R = -0.565; P < .01). By
      confocal immunohistochemistry, both human and mouse AAA smooth muscle cells
      (smooth muscle alpha-actin positive) and macrophages (CD68 positive or Mac-2
      positive) expressed aromatase. CONCLUSIONS: The protective effect of female
      gender on AAAs is due to estrogen synthesis and requires the presence of both
      ovarian and extragonadal/peripheral aromatase. Peripheral estrogen synthesis
      accounts for roughly half of the protective effect of female gender. If
      peripheral aromatase could be targeted, high levels of local estrogen could be
      produced and may avoid the side effects of systemic estrogen.

PMID- 24582703
TI  - Despite normal arteriogenic and angiogenic responses, hind limb perfusion
      recovery and necrotic and fibroadipose tissue clearance are impaired in matrix
      metalloproteinase 9-deficient mice.
AB  - OBJECTIVE: The relative contributions of arteriogenesis, angiogenesis, and
      ischemic muscle tissue composition toward reperfusion after arterial occlusion
      are largely unknown. Differential loss of bone marrow-derived cell (BMC) matrix
      metalloproteinase 9 (MMP9), which has been implicated in all of these processes,
      was used to assess the relative contributions of these processes during limb
      reperfusion. METHODS: We compared collateral growth (arteriogenesis), capillary
      growth (angiogenesis), and ischemic muscle tissue composition after femoral
      artery ligation in FVB/NJ mice that had been reconstituted with bone marrow from
      wild-type or MMP9(-/-) mice. RESULTS: Laser Doppler perfusion imaging confirmed
      decreased reperfusion capacity in mice with BMC-specific loss of MMP9; however,
      collateral arteriogenesis was not affected. Furthermore, when accounting for the
      fact that muscle tissue composition changes markedly with ischemia (ie, necrotic,
      fibroadipose, and regenerating tissue regions are present), angiogenesis was also
      unaffected. Instead, BMC-specific loss of MMP9 caused an increase in the
      proportion of necrotic and fibroadipose tissue, which showed the strongest
      correlation with poor perfusion recovery. Similarly, the reciprocal loss of MMP9
      from non-BMCs showed similar deficits in perfusion and tissue composition without
      affecting arteriogenesis. CONCLUSIONS: By concurrently analyzing arteriogenesis,
      angiogenesis, and ischemic tissue composition, we determined that the loss of BMC
      derived or non-BMC-derived MMP9 impairs necrotic and fibroadipose tissue
      clearance after femoral artery ligation, despite normal arteriogenic and
      angiogenic vascular growth. These findings imply that therapeutic
      revascularization strategies for treating peripheral arterial disease may benefit
      from additionally targeting necrotic tissue clearance or skeletal muscle
      regeneration, or both.

PMID- 24582704
TI  - Problematic Internet use in Parkinson's disease.
AB  - BACKGROUND: Problematic Internet use (PIU) has been associated with impulse
      control disorders (ICDs), and postulated to share characteristics of a behavioral
      addiction with both impulsive and compulsive features. However, Internet use has
      not been previously systematically studied in Parkinson's disease. AIM: We
      explore Internet use in PD patients with and without ICDs and matched healthy
      controls. We hypothesize that the PD-ICD patients will spend more time on the
      Internet, accessing websites related to their ICDs, compared with PD patients
      without ICDs and healthy volunteers. METHODS: Our study is the first to
      systematically explore problematic Internet use in patients with PD, with and
      without ICDs. Twenty-nine PD patients with ICDs, twenty PD patients without ICDs
      and nineteen healthy controls were recruited. All participants endorsed using the
      Internet for non-essential purposes. They underwent a semi-structured interview
      and completed questionnaires including the Yale-Brown Obsessive Compulsive Scale
      adapted for Internet use (Y-BOCS-Internet). RESULTS: PD-ICD patients scored
      significantly higher on the Y-BOCS-Internet than the PD-control and HV groups (PD
      ICD: 13.69; PD-control: 5.42; HV: 4.70; p < 0.0001). Compared to PD controls and
      HV groups, the PD-ICD group spent more time on the Internet (p = 0.0001),
      described significantly more effort to resist Internet use (p = 0.0002), thoughts
      about Internet use (p < 0.0001) and its interference with their life functioning
      (p = 0.0025). DISCUSSION: Our results suggest that PD patients with ICDs have a
      relative increased tendency towards excessive Internet use compared to those
      without ICDs and healthy controls. Clinicians should actively screen for
      excessive Internet use in patients with ICDs.

PMID- 24582705
TI  - Clinical and pathologic presentation in Parkinson's disease by apolipoprotein e4
      allele status.
AB  - BACKGROUND: Apolipoprotein (APOE) e4 allele status has been linked to clinical
      presentation and progression in Alzheimer's disease; however, evidence for a role
      of APOE e4 in Parkinson's disease (PD) remains largely inconclusive. In this
      analysis we explored potential significant associations between APOE e4 allele
      status and characteristics of clinical presentation in patients with PD. METHODS:
      Data came from 424 subjects evaluated using the Uniform Data Set (UDS) assessment
      collected by the National Alzheimer's Coordinating Center. Subjects had a known
      year of diagnosis of PD and experienced change in motor function prior to any
      change in cognition. Linear and logistic regression were used to model the
      association between APOE e4 carrier status and clinical characteristics including
      measures of cognitive decline and motor and neuropsychiatric symptoms. Amyloid
      burden was also evaluated for a subset of patients who died and consented to
      autopsy. RESULTS: Odds of dementia were higher in APOE e4 carriers (OR = 5.15),
      and, on average, APOE e4 carriers scored two points worse on tests of episodic
      memory and the Clinical Dementia Rating Sum of Boxes assessment. There was little
      evidence to support an association between e4 carrier status and severity of
      motor features, and, of the four neuropsychiatric symptoms evaluated, only
      presence of hallucinations was significantly associated with APOE e4 carrier
      status (OR = 5.29). Neuropathology data revealed higher frequencies of neuritic
      and diffuse amyloid plaques in APOE e4 carriers compared to non-carriers.
      CONCLUSIONS: APOE e4 allele status is associated with dementia and severity of
      Alzheimer's disease pathologic features in PD.

PMID- 24582706
TI  - Incisterols, highly degraded marine sterols, are a new chemotype of PXR agonists.
AB  - During the chromatographic purification of organic extracts obtained from
      Plakortis cfr. lita we obtained three highly degraded steroid derivatives, the
      known incisterol A2 (1) and the new incisterols A5 (2) and A6 (3). The new
      compounds were characterized basing on NMR and MS evidences along with comparison
      with model compounds. Incisterol A5 proved to bear a 17S-ethyl-15E,18-diene
      (incisterol numbering system) side chain, found for the first time in a marine
      organism. The new incisterols A5 and A6 proved to be potent inducers of
      transactivation of the pregnane X receptor (PXR) and they also stimulate the
      expression of CYP7A4 and MDR1 with a potency comparable to that of Rifaximin.
      These observations prompt to consider incisterols A5 and A6 as new potent
      agonists of PXR. On the other hand, the 17R-methyl analogue incisterol A2 shows
      only a poor PXR agonist activity. Molecular docking simulations elucidated the
      binding mechanism of the active incisterols in the ligand binding domain of PXR. 

PMID- 24582707
TI  - Investigation on the synthesis of 25-hydroxycholesterol.
AB  - A very efficient and environmentally benign method has been developed for the
      synthesis of 25-hydroxycholesterol. The reaction was performed in THF-water (4:1,
      v/v) using NBS as the brominating agent, followed by the easy reduction of C-Br
      with lithium aluminum hydride in THF, to yield the final product corresponding to
      a Markovnikov's rule. Excellent yields and regioselectivity have been obtained. 

PMID- 24582708
TI  - Contrasted survival under field or controlled conditions displays associations
      between mRNA levels of candidate genes and response to OsHV-1 infection in the
      Pacific oyster Crassostrea gigas.
AB  - Pacific oyster Crassostrea gigas suffers from chronic or sporadic mortality
      outbreaks worldwide, resulting from infectious diseases and/or physiological
      disorders triggered by environmental factors. Since 2008, ostreid herpesvirus
      OsHV-1 MUVar has been identified as the main agent responsible for mass mortality
      of juvenile oysters in Europe. Previous studies of genome-wide expression
      profiling have provided candidate genes that potentially contribute to
      genetically-based resistance to summer mortality. To assess their value in
      determining resistance to the juvenile mass mortality that has occurred in France
      since 2008, we analyzed the expression of 17 candidate genes in an experimental
      infection by OsHV-1 MUVar, and in an in vivo field experiment. Individual
      quantification of mRNA levels of 10 out of the 17 targeted genes revealed
      significant variation, of which 7 genes were showed differences between
      conditions that created significant differences in mortality, and 6 depended on
      the number of OsHV-1 genome copies individually quantified in mantle tissue.
      Complex SOD metalloenzymes known to be part of the antioxidant defense strategies
      may at least partly determine susceptibility or resistance to OsHV-1-associated
      mortality. Furthermore, inhibitor 2 of NF-kappaB, termed CgIkappaB2, exhibited
      highly significant variation of mRNA levels depending on OsHV-1 load in both
      experiments, suggesting its implication in the antiviral immune response of C.
      gigas. Our results suggest that CgIkappaB2 expression would make a good starting
      point for further functional research and that it could be used in marker
      assisted selection. 

PMID- 24582709
TI  - Free energy analysis of conductivity and charge selectivity of M2GlyR-derived
      synthetic channels.
AB  - Significant progresses have been made in the design, synthesis, modeling and in
      vitro testing of channel-forming peptides derived from the second transmembrane
      domain of the alpha-subunit of the glycine receptor (GlyR). The latest designs,
      including p22 (KKKKP ARVGL GITTV LTMTT QS), are highly soluble in water with
      minimal aggregation propensity and insert efficiently into cell membranes to form
      highly conductive ion channels. The last obstacle to a potential lead sequence
      for channel replacement treatment of CF patients is achieving adequate chloride
      selectivity. We have performed free energy simulation to analyze the conductance
      and charge selectivity of M2GlyR-derived synthetic channels. The results reveal
      that the pentameric p22 pore is non-selective. Moderate barriers for permeation
      of both K(+) and Cl(-) are dominated by the desolvation cost. Despite previous
      evidence suggesting a potential role of threonine side chains in anion
      selectivity, the hydroxyl group is not a good surrogate of water for coordinating
      these ions. We have also tested initial ideas of introducing additional rings of
      positive changes to various positions along the pore to increase anion
      selectivity. The results support the feasibility of achieving anion selectivity
      by modifying the electrostatic properties of the pore, but at the same time
      suggest that the peptide assembly and pore topology may also be dramatically
      modified, which could abolish the effects of modified electrostatics on anion
      selectivity. This was confirmed by subsequent two-electrode voltage clamp
      measurements showing that none of the tested mono-, di- and tri-Dap substituted
      sequences was selective. The current study thus highlights the importance of
      controlling channel topology besides modifying pore electrostatics for achieving
      anion selectivity. Several strategies are now being explored in our continued
      efforts to design an anion selective peptide channel with suitable biophysical,
      physiological and pharmacological properties as a potential treatment modality
      for channel replacement therapy. This article is part of a Special Issue
      entitled: Interfacially Active Peptides and Proteins. Guest Editors: William C.
      Wimley and Kalina Hristova. 

PMID- 24582710
TI  - Phase coexistence in films composed of DLPC and DPPC: a comparison between
      different model membrane systems.
AB  - For the biophysical study of membranes, a variety of model systems have been used
      to measure the different parameters and to extract general principles concerning
      processes that may occur in cellular membranes. However, there are very few
      reports in which the results obtained with the different models have been
      compared. In this investigation, we quantitatively compared the phase coexistence
      in Langmuir monolayers, freestanding bilayers and supported films composed of a
      lipid mixture of DLPC and DPPC. Two-phase segregation was observed in most of the
      systems for a wide range of lipid proportions using fluorescence microscopy. The
      lipid composition of the coexisting phases was determined and the distribution
      coefficient of the fluorescent probe in each phase was quantified, in order to
      explore their thermodynamic properties. The comparison between systems was
      carried out at 30mN/m, since it is accepted that at this or higher lateral
      pressures, the mean molecular area in bilayers is equivalent to that observed in
      monolayers. Our study showed that while Langmuir monolayers and giant unilamellar
      vesicles had a similar phase behavior, supported films showed a different
      composition of the phases with the distribution coefficient of the fluorescent
      probe being close to unity. Our results suggest that, in supported membranes, the
      presence of the rigid substrate may have led to a stiffening of the liquid
      expanded phase due to a loss in the degrees of freedom of the lipids as a
      consequence of the proximity of the solid material.

PMID- 24582711
TI  - Physiological variables affecting surface film formation by native lamellar body
      like pulmonary surfactant particles.
AB  - Pulmonary surfactant (PS) is a surface active complex of lipids and proteins that
      prevents the alveolar structures from collapsing and reduces the work of
      breathing by lowering the surface tension at the alveolar air-liquid interface
      (ALI). Surfactant is synthesized by the alveolar type II (AT II) cells, and it is
      stored in specialized organelles, the lamellar bodies (LBs), as tightly packed
      lipid bilayers. Upon secretion into the alveolar lining fluid, a large fraction
      of these particles retain most of their packed lamellar structure, giving rise to
      the term lamellar body like-particles (LBPs). Due to their stability in aqueous
      media, freshly secreted LBPs can be harvested from AT II cell preparations.
      However, when LBPs get in contact with an ALI, they quickly and spontaneously
      adsorb into a highly organized surface film. In the present study we investigated
      the adsorptive capacity of LBPs at an ALI under relevant physiological parameters
      that characterize the alveolar environment in homeostatic or in pathological
      conditions. Adsorption of LBPs at an ALI is highly sensitive to pH, temperature
      and albumin concentration and to a relatively lesser extent to changes in
      osmolarity or Ca(2+) concentrations in the physiological range. Furthermore,
      proteolysis of LBPs significantly decreases their adsorptive capacity confirming
      the important role of surfactant proteins in the formation of surface active
      films. 

PMID- 24582712
TI  - A marker-free automatic alignment method based on scale-invariant features.
AB  - In electron tomography, alignment accuracy is critical for high-resolution
      reconstruction. However, the automatic alignment of a tilt series without
      fiducial markers remains a challenge. Here, we propose a new alignment method
      based on Scale-Invariant Feature Transform (SIFT) for marker-free alignment. The
      method covers the detection and localization of interest points (features),
      feature matching, feature tracking and optimization of projection parameters. The
      proposed method implements a highly reliable matching strategy and tracking model
      to detect a huge number of feature tracks. Furthermore, an incremental bundle
      adjustment method is devised to tolerate noise data and ensure the accurate
      estimation of projection parameters. Our method was evaluated with a number of
      experimental data, and the results exhibit an improved alignment accuracy
      comparable with current fiducial marker alignment and subsequent higher
      resolution of tomography. 

PMID- 24582713
TI  - Anemia management trends in hospital-based dialysis centers (HBDCs), 2010 to
      2013.
AB  - BACKGROUND: Few data have been reported on anemia management practices in
      hospital-based dialysis centers (HBDCs), which are uniquely different from other
      freestanding dialysis centers. Examining data from HBDCs would help determine if
      HBDCs and the general US dialysis population have similar trends related to how
      anemia is managed in dialysis patients. OBJECTIVE: Given recent changes in the
      prescribing information of erythropoiesis-stimulating agents (ESAs) and in end
      stage renal disease-related health policy and reimbursement, this study describes
      trends in anemia management practices in HBDCs from January 2010 through March
      2013. METHODS: Electronic medical records of 5404 adult hemodialysis patients in
      50 US-based HBDCs were analyzed retrospectively. Patients included in the study
      cohort were aged >=18 years and had at least 1 hemoglobin (Hb) measurement and 1
      dose of an ESA between January 2010 and March 2013. End points included Hb
      concentration, darbepoetin alfa dosing, epoetin alfa dosing, and iron biomarkers
      (transferrin saturation and ferritin) and dosing. RESULTS: From 2010 to 2013,
      mean monthly Hb levels declined from 11.4 to 10.7 g/dL; the percentage of
      patients with mean monthly Hb levels <10 g/dL increased from 11.3% to 24.4%; and
      the percentage of patients with mean monthly Hb levels >12 g/dL declined from
      30.1% to 11.2%. The median darbepoetin alfa cumulative 4-week dose also declined
      38.8%, and the weekly epoetin alfa dose declined 24%. From January 2010 to March
      2013, the percentage of patients with transferrin saturation >30% increased from
      35.8% to 43.6%, the percentage of patients with ferritin levels >500 ng/mL
      increased from 62.0% to 77.9%, the percentage of patients with ferritin levels
      >=800 ng/mL increased from 28.9% to 47.3%, and the median cumulative 4-week
      intravenous iron dose increased 50%. CONCLUSIONS: These study results support
      growing evidence that meaningful changes have occurred over the last 3 years in
      how anemia is clinically managed in US hemodialysis patients. Study limitations
      include that changes in patient clinical/demographic characteristics over time
      were not controlled for and that study findings may not be applicable to HBDCs
      that have different patient populations and/or do not use an electronic medical
      record system. Continuing to evaluate anemia management practices in HBDCs would
      provide additional information on the risks and benefits of anemia care.
      Consistent with national data, the findings from this study indicate that from
      2010 to 2013, HBDCs modified anemia management practices for dialysis patients,
      as evidenced by reductions in mean monthly Hb levels and ESA dosing and by
      increases in iron biomarkers and dosing.

PMID- 24582714
TI  - Calcineurin inhibitors stimulate and mycophenolic acid inhibits replication of
      hepatitis E virus.
AB  - BACKGROUND & AIMS: Many recipients of organ transplants develop chronic
      hepatitis, due to infection with the hepatitis E virus (HEV). Although chronic
      HEV infection is generally associated with immunosuppressive therapies, little is
      known about how different immunosuppressants affect HEV infection. METHODS: A
      subgenomic HEV replication model, in which expression of a luciferase reporter
      gene is measured, and a full-length infection model were used. We studied the
      effects of different immunosuppressants, including steroids, calcineurin
      inhibitors (tacrolimus [FK506] and cyclosporin A), and mycophenolic acid (MPA, an
      inhibitor of inosine monophosphate dehydrogenase) on HEV replication in human
      hepatoma cell line Huh7. Expression of cyclophilins A and B (the targets of
      cyclosporin A) were knocked down using small hairpin RNAs. RESULTS: Steroids had
      no significant effect on HEV replication. Cyclosporin A promoted replication of
      HEV in the subgenomic and infectious models. Knockdown of cyclophilin A and B
      increased levels of HEV genomic RNA by 4.0- +/- 0.6-fold and 7.2- +/- 1.9-fold,
      respectively (n = 6; P < .05). A high dose of FK506 promoted infection of liver
      cells with HEV. In contrast, MPA inhibited HEV replication. Incubation of cells
      with guanosine blocked the antiviral activity of MPA, indicating that the
      antiviral effects of this drug involve nucleotide depletion. The combination of
      MPA and ribavirin had a greater ability to inhibit HEV replication than MPA or
      ribavirin alone. CONCLUSIONS: Cyclophilins A and B inhibit replication of HEV;
      this might explain the ability of cyclosporin A to promote HEV infection. On the
      other hand, the immunosuppressant MPA inhibits HEV replication. These findings
      should be considered when physicians select immunosuppressive therapies for
      recipients of organ transplants who are infected with HEV.

PMID- 24582715
TI  - New insights into the mechanism of neurolathyrism: L-beta-ODAP triggers [Ca2+]i
      accumulation and cell death in primary motor neurons through transient receptor
      potential channels and metabotropic glutamate receptors.
AB  - Neurolathyrism is a motor neuron (MN) disease caused by beta-N-oxalyl-L
      alpha,beta-diaminopropionic acid (L-beta-ODAP), an AMPA receptor agonist. L-beta
      ODAP caused a prolonged rise of intracellular Ca(2+) ([Ca(2+)]i) in rat spinal
      cord MNs, and the [Ca(2+)]i accumulation was inversely proportional to the MN's
      life span. The [Ca(2+)]i rise induced by L-beta-ODAP or (S)-AMPA was antagonized
      completely by NBQX, an AMPA-receptor blocker. However, blocking the L-type Ca(2+)
      channel with nifedipine significantly lowered [Ca(2+)]i induced by (S)-AMPA, but
      not that by L-beta-ODAP. Tetrodotoxin completely extinguished the [Ca(2+)]i rise
      induced by (S)-AMPA or kainic acid, whereas that induced by L-beta-ODAP was only
      attenuated by 65.6+/-6% indicating the prominent involvement of voltage
      independent Ca(2+) entry. The tetrodotoxin-resistant [Ca(2+)]i induced by L-beta
      ODAP was blocked by 2-APB, Gd(3+), La(3+), 1-(beta-[3-(4-methoxy-phenyl)propoxy]
      4-methoxyphenethyl)-1H-imidazole hydrochloride (SKF-96365) and flufenamic acid,
      which all are blockers of the transient receptor potential (TRP) channels.
      Blockers of group I metabotropic glutamate receptors (mGluR I), 7
      (hydroxyiminocyclopropan[b]chromen-1alpha-carboxylate ethyl ester (CPCCPEt) and 2
      methyl-6-(phenylethynyl)-pyridine (MPEP) also lowered the [Ca(2+)]i rise by L
      beta-ODAP. MN cell death induced by L-beta-ODAP was prolonged significantly with
      SKF-96365 as well as NBQX. The results show the involvement of TRPs and mGluR I
      in L-beta-ODAP-induced MN toxicity through prolonged [Ca(2+)]i mobilization, a
      unique characteristic of this neurotoxin. 

PMID- 24582716
TI  - Macrophage alteration induced by inflammatory toxins isolated from Tityus
      discrepans scorpion venom. The role of Na(+)/Ca(2+) exchangers.
AB  - We study the effect of all Tityus discrepans venom components on macrophage
      alterations. Only seven toxins called "Inflammatory Toxin" (InfTx1-7) induced
      cell changes. Incubation with InfTx1 through InfTx5 rose macrophage NO level at 2
      h toxin exposure. Cells rose NO release by 4 h exposure with InfTx2 and InfTx5,
      the NO levels reached concentrations similar or higher than the induced by
      lipopolysaccharides (LPS) incubation. InfTx2, -6 and -7 increased cell TNF-alpha
      release. InfTx2 as LPS roses cell TNF-alpha secretion gradually in time.
      Macrophages were loaded with fluorescent dyes, exposed to all toxins and observed
      with a 3D wide field deconvolution setup. Cells exposed to whole venom or InfTx4
      through InfTx7 developed pseudopodia, cytoplasm prolongations, blebs, and loss
      their rounded form. The molecular masses and N-terminal sequences of InfTx4
      through InfTx7 were analyzed by MALDI-TOF mass spectrometry and Edman
      degradation. InfTx4-7 induced a remarkable increase of intracellular Ca(2+)
      levels ([Ca(2+)]i), measured as a rise of normalized cell green fluorescence
      intensity (FI) *2.7, *2.6, *95 and *2.9 the controls, respectively. InfTx6-7
      action mechanisms were studied under different conditions. Results suggested that
      InfTx6 interact with a membrane sodium channel inducing cell depolarization with
      a consequent increase on intracellular [Na(+)], this would activate Na(+)/Ca(2+)
      exchanger 3 (NCX) in the reverse mode and the phospholipase C inositol 1,4,5
      trisphosphate (PLC-IP3) signaling pathway inducing [Ca(2+)]i overload. Inftx7
      should activate the NCX in reverse mode and/or should activate the Na(+)/H(+)
      exchanger, increasing intracellular [Na(+)] which indirectly induce the
      activation of NCX3rv and the PLC-IP3 signaling pathway. All these mechanisms
      would cooperate with the [Ca(2+)]i overload. A rise of [Ca(2+)]i activates the
      synthesis and secretion of inflammatory molecules like TNF-alpha, which in turn,
      increases the gene transcription for inducible nitric oxide synthase, resulting
      on NO production. 

PMID- 24582717
TI  - Pulmonary functional and morphological damage after exposure to tripoli dust.
AB  - Tripoli is a microcrystalline siliceous rock used to polish metals and precious
      stones. Its inhalation has been associated with increased prevalence of breathing
      complaints and pneumoconiosis. However, its acute human exposure has not been so
      far studied. We aimed at evaluating the putative mechanical, morphological,
      biochemical and inflammatory lung damage in mice acutely exposed to Tripoli dust.
      BALB/c mice were randomly assigned to 2 groups: In control group (CTRL, n=6)
      animals received intratracheally (i.t.) 0.9% NaCl (50MUl), while Tripoli group
      (TRIP, n=15) received 20mg of Tripoli powder diluted in 50MUL of saline i.t. The
      experiments were done 15 days later. TRIP mice showed higher pulmonary mechanical
      impedance, polymorphonuclear cells, TNF-alpha, IL1-beta and IL-6 than CTRL. TRIP
      presented granulomatous nodules containing collagenous fibers that occupied 35%
      of the lung tissue area. In conclusion, acute exposure to Tripoli dust triggered
      important lung damage in mice lungs that if found in human workers could trigger
      severe illness. 

PMID- 24582718
TI  - Is there a competition for oxygen availability between respiratory and limb
      muscles?
AB  - If a competition between the oxygen demands of limb and respiratory muscles
      happens, hypoxia may favor redistribution of blood flow from peripheral to
      respiratory muscles during heavy exercise. This hypothesis was tested in eighteen
      lowlanders and 27 highlanders at 4350m altitude. During an incremental exercise,
      the regional tissue oxygen saturation (rSO2) and tissue hemoglobin concentration
      ([Hbt]) of the intercostal muscles and vastus medialis were monitored
      simultaneously by NIRS. The intercostal and vastus medialis rSO2 values were
      lower at altitude than at sea level (-10%, p<0.001) and decreased similarly
      during incremental exercise (p<0.001) while [Hbt] values increased. At maximal
      exercise, the intercostal rSO2 was lower than the vastus medialis rSO2 in
      lowlanders (-7%, p<0.001). In highlanders the time patterns were similar but
      intercostal rSO2 was less decreased at exercise (p<0.05). Maximal exercise
      performed in hypoxia did not alter the kinetics of rSO2 and [Hbt] in peripheral
      muscles. These findings do not favor the hypothesis of blood flow redistribution.

PMID- 24582719
TI  - Antagonism of substance P and perception of breathlessness in patients with
      chronic obstructive pulmonary disease.
AB  - The objective of this study was to investigate whether substance P, an excitatory
      neuropeptide, modulates the perception of breathlessness by administering
      aprepitant, a selective antagonist that blocks neurokinin (NK)-1 receptor
      signaling. Individual targeted resistive load breathing (RLB) was used to provoke
      breathlessness. In Study 1, sixteen patients (age, 70+/-6 years) with chronic
      obstructive pulmonary disease (COPD) reported similar ratings of breathlessness
      during RLB between oral aprepitant (125mg) and placebo. After aprepitant, but not
      with placebo, there were significant increases in blood levels of substance P
      (+54+/-39%) and beta-endorphin (+27+/-17%). A similar design was used in Study 2
      except that naloxone (10mg) was administered intravenously prior to RLB to block
      any effect of endogenous opioids. Nine patients with COPD reported comparable
      breathlessness ratings during RLB between aprepitant and placebo. Our results do
      not support a role for the substance P-NK-1 pathway in the perception of
      breathlessness in patients with COPD. With selective antagonism of NK-1
      signaling, there was co-transmission of substance P and beta-endorphin
      neuropeptides. 

PMID- 24582720
TI  - Atrioesophageal fistula in the era of atrial fibrillation ablation: a review.
AB  - The purpose of this review is to understand the epidemiology, clinical features,
      etiopathogenesis, and management of atrioesophageal fistula (AEF) after atrial
      fibrillation (AF) ablation. The incidence of AEF after AF ablation is 0.015%
      0.04%. The principal clinical features include fever, dysphagia, upper
      gastrointestinal bleeding, sepsis, and embolic strokes. The close proximity of
      the esophagus to the posterior left atrial wall is responsible for esophageal
      injury during ablation. Prophylactic proton pump inhibitors, esophageal
      temperature monitoring, visualization of the esophagus during catheter ablation,
      esophageal protection devices, and avoidance of energy delivery in close
      proximity to the esophagus play an important role in preventing esophageal
      injury. Early surgical repair or esophageal stenting are the mainstay of
      treatment. Eliminating esophageal injury during AF ablation is of utmost
      importance in preventing AEF. A high index of suspicion and early intervention is
      necessary to prevent fatal outcomes. 

PMID- 24582721
TI  - Comparing the 'new' R2CHADS2 with the 'old' CHA2DS2-VASc scores for predicting
      thromboembolism in patients undergoing atrial fibrillation ablation: new does not
      mean better.

PMID- 24582722
TI  - Optical coherence tomography imaging of Takayasu coronary arteritis.

PMID- 24582723
TI  - Evaluation of suspected ischemic heart disease in symptomatic women.
AB  - There is a wealth of evidence about the role of a variety of diagnostic testing
      modalities to define coronary artery disease (CAD) risk in women presenting for
      evaluation of suspected myocardial ischemia. The exercise electrocardiogram (ECG)
      is the core index procedure, which can define risk in women capable of performing
      maximal exercise. Stress imaging, using echocardiography or myocardial perfusion
      single-photon emission computed tomography/positron emission tomography, is
      useful for symptomatic women with an abnormal resting ECG or for those who are
      functionally disabled. For women with low-risk stress imaging findings, there is
      a very low risk of CAD events, usually < 1%. There is a gradient relationship
      between the extent and severity of inducible abnormalities and CAD event risk.
      Women at high risk are those defined as having moderate to severely abnormal wall
      motion or abnormal perfusion imaging findings. In addition to stress imaging, the
      evidence of the relationship between CAD extent and severity and prognosis has
      been clearly defined with coronary computed tomographic angiography. In women,
      prognosis for those with mild but nonobstructive CAD is higher when compared with
      those without any CAD. The current evidence base clearly supports that women
      presenting with chest pain can benefit from one of the commonly applied
      diagnostic testing modalities. 

PMID- 24582725
TI  - R2CHADS2 score and thromboembolic events after catheter ablation of atrial
      fibrillation in comparison with the CHA2DS2-VASc score.
AB  - BACKGROUND: A new risk model, the R2CHADS2 (Renal Dysfunction, Congestive Heart
      Failure, Hypertension, Age, Diabetes, Stroke/Transient Ischemic Attack) score,
      was proposed to be a powerful scoring scheme in predicting stroke or systemic
      embolism in atrial fibrillation (AF). The goal of the present study is to
      validate the usefulness of the R2CHADS2 score among patients with AF after
      catheter ablation. We also aimed to compare the accuracy of the CHA2DS2-VASc
      (Congestive Heart Failure, Hypertension, Age [>= 75 y], Diabetes,
      Stroke/Transient Ischemic Attack, Vascular Disease, Age [65-74 y], Sex [Female])
      and R2CHADS2 scores for risk stratification of thromboembolic (TE) events after
      ablation procedures. METHODS: We enrolled a total of 526 patients with AF who
      underwent catheter ablation. The clinical end point was the occurrence of TE
      events (ischemic stroke, transient ischemic attack, or other systemic embolisms)
      during the postablation follow-up. RESULTS: During a follow-up of 37.5 +/- 21.3
      months, 14 patients (2.7%) experienced TE events. The R2CHADS2 score was an
      independent predictor of TE events in the multivariate analysis. Patients with an
      R2CHADS2 score of > 2 had a higher event rate compared with those with a score of
      0 or 1 (0.5% vs 7.7%). The areas under the receiver operating characteristic
      (ROC) curves of CHA2DS2-VASc and R2CHADS2 scores in predicting TE events were
      0.832 and 0.872, respectively. The difference between these 2 curves did not
      reach statistical significance (P = 0.338). In addition, the R2CHADS2 score did
      not improve net stroke risk reclassification over the CHA2DS2-VASc score (net
      reclassification improvement, -0.9%; P = 0.948). CONCLUSIONS: The R2CHADS2 and
      CHA2DS2-VASc scores could be used to predict TE events for patients with AF
      undergoing catheter ablation. The predictive accuracy of both scores were similar
      in this relatively small cohort undergoing ablation.

PMID- 24582724
TI  - Sex-specific factors in microvascular angina.
AB  - In women presenting for evaluation of suspected ischemic symptoms, a diagnosis of
      normal coronary arteries is 5 times more common than it is in men. These women
      are often labelled as having cardiac syndrome X, and a subset of them have
      microvascular angina caused by microvascular coronary dysfunction (MCD). MCD is
      not benign and is associated with an annual 2.5% cardiac event rate. Noninvasive
      testing for MCD remains insensitive, although newer imaging modalities, such as
      adenosine cardiac magnetic resonance imaging, appear promising. The gold standard
      for diagnosis of MCD is coronary reactivity testing, an invasive technique that
      is not available in many countries. With regard to treatment, large-scale trials
      are lacking. Although research is ongoing, the current platform of therapy
      consists of antiangina, antiplatelet, and endothelium-modifying agents (primarily
      angiotensin-converting enzyme inhibitors and statins). 

PMID- 24582726
TI  - Identification and characterization of a novel multicopper oxidase from
      Acidomyces acidophilus with ferroxidase activity.
AB  - A new multicopper oxidase gene AaMco1 was identified in Acidomyces acidophilus, a
      pigmented extremophile ascomycete originally isolated from acidic water. Sequence
      analysis revealed that it encodes a 682 amino acid protein with an apparent
      molecular mass of 85 kDa as determined by denaturing SDS-PAGE. Interestingly,
      AaMco1 has a predicted N-terminal transmembrane helix and no signal peptide. To
      obtain an active and soluble protein, AaMco1 was truncated at its N-terminal to
      remove the transmembrane helix, but even in this form the protein was found in
      the insoluble fraction. AaMco1 and its truncated form were then denatured,
      purified and renatured before characterization. Structural analysis and protein
      characterization by enzymatic assays indicate that AaMco1 has ferroxidase
      activity. AaMco1 is also able to oxidize the DMPPDA compound and could be part of
      a new phylogenetic cluster, the ascomycete MCOs family, described for the first
      time here.

PMID- 24582727
TI  - Laparoscopic incisional hernia repair: long term results.
AB  - OBJECTIVE: The aim of this prospective monocenter study was to evaluate the long
      term results of laparoscopic treatment of incisional hernias using intra
      peritoneal prosthetic mesh. PATIENTS AND METHODS: Seventy-seven patients
      underwent laparoscopic treatment of incisional hernia between January 2002 and
      January 2008. All patients were followed for at least five years after surgery.
      The parameters assessed were hernia recurrences and post-operative pain. In case
      of doubt as to the diagnosis of recurrence or pain, a CT examination was
      performed. RESULTS: Nine patients were excluded: four patients refused to
      participate in the study and five died of unrelated disease during follow-up.
      Sixty-eight patients (89.7%) were followed for a mean of 92.3 (+/- 19.8)months.
      Mean age of patients was 58 (+/- 11.3)years. There were no deaths and no
      conversions. The mean operative time was 104 (+/- 48)minutes. The morbidity rate
      was 13.2%. Major complications included one case each of mesh infection, post
      operative peritonitis (bowel injury), and surgical site pain requiring revisional
      surgery. Five patients developed seroma. The mean duration of hospitalization was
      4.5 (+/- 2.3) days. The long-term recurrence rate was 8.8%. The average interval
      to onset of recurrence was 45.8 (+/- 31.1)months. Trocar site hernias were
      observed in three patients. Four patients had post-operative pain requiring long
      term medical treatment. CONCLUSION: Laparoscopic incisional hernia repair using
      intra-peritoneal prosthetic mesh is a safe technique with satisfactory long-term
      outcome. One major complication occurred: bowel injury. Suture closure of 10mm
      trocar sites should be routine.

PMID- 24582728
TI  - Radiofrequency ablation for colorectal liver metastases.
AB  - The management of hepatic metastases from colorectal cancer (HMCRC) is multimodal
      including chemotherapy, surgical resection, radiation therapy, and focused
      destruction technologies. Radiofrequency ablation (RFA) is the most commonly used
      focused destruction technology. It represents a therapeutic option that may be
      potentially curative in cases where surgical excision is contra-indicated. It
      also increases the number of candidates for surgical resection among patients
      whose liver metastases were initially deemed unresectable. This article explains
      the techniques, indications, and results of radiofrequency ablation in the
      treatment of hepatic colorectal metastases. 

PMID- 24582729
TI  - Ex vivo detection of CD8 T cells specific for H-Y minor histocompatibility
      antigens in allogeneic hematopoietic stem cell transplant recipients.
AB  - Immunologic disparities between minor histocompatibility antigen (mHAg) genes on
      Y (H-Y) and X (H-X) chromosomes contribute to graft-versus-host disease (GVHD)
      and graft-versus-leukemia (GVL) effects observed in male recipients of a female
      donor (FtoM) hematopoietic stem cell transplant (HCT). Using in silico prediction
      tools, a panel of HLA-A0201 restricted H-Y peptides was synthesized. Expression
      of CD137 was monitored on CD8(+) T cells after brief stimulation with the H-Y
      peptides in FtoM HLA-A0201 HCT recipients (N=29), and control groups (HLA-A0201
      MtoM [N=18], non-HLA-A0201 FtoM [N=14], and HLA-A0201 female volunteers [N=25]).
      Specific H-Y responses were significantly greater in HLA-A0201 FtoM than
      controls. CD8(+) T-cell responses to novel H-Y epitopes were shared among
      multiple patients, showing marked CD45RA(+)CD27 cytolytic effector profiles.
      These data represent a proof of concept for our in silico/ex vivo CD8(+) T-cell
      based approach of prediction and validation of H-Y mHAgs in HCT recipients, which
      may facilitate prospective studies to identify targets/biomarkers of GVHD/GVL. 

PMID- 24582730
TI  - Does methamphetamine affect bone metabolism?
AB  - There is a close relationship between the central nervous system activity and
      bone metabolism. Therefore, methamphetamine (METH), which stimulates the central
      nervous system, is expected to affect bone turnover. The aim of this study was to
      investigate the role of METH in bone metabolism. Mice were divided into 3 groups,
      the control group receiving saline injections, and the 5 and 10mg/kg METH groups
      (n=6 in each group). All groups received an injection of saline or METH every
      other day for 8 weeks. Bone mineral density (BMD) was assessed by X-ray computed
      tomography. We examined biochemical markers and histomorphometric changes in the
      second cancellous bone of the left femoral distal end. The animals that were
      administered 5mg/kg METH showed an increased locomotor activity, whereas those
      receiving 10mg/kg displayed an abnormal and stereotyped behavior. Serum calcium
      and phosphorus concentrations were normal compared to the controls, whereas the
      serum protein concentration was lower in the METH groups. BMD was unchanged in
      all groups. Bone formation markers such as alkaline phosphatase and osteocalcin
      significantly increased in the 5mg/kg METH group, but not in the 10mg/kg METH
      group. In contrast, bone resorption markers such as C-terminal telopeptides of
      type I collagen and tartrate-resistant acid phosphatase 5b did not change in any
      of the METH groups. Histomorphometric analyses were consistent with the
      biochemical markers data. A significant increase in osteoblasts, especially in
      type III osteoblasts, was observed in the 5mg/kg METH group, whereas other
      parameters of bone resorption and mineralization remained unchanged. These
      results indicate that bone remodeling in this group was unbalanced. In contrast,
      in the 10mg/kg METH group, some parameters of bone formation were significantly
      or slightly decreased, suggesting a low turnover metabolism. Taken together, our
      results suggest that METH had distinct dose-dependent effects on bone turnover
      and that METH might induce adverse effects, leading to osteoporosis. 

PMID- 24582732
TI  - The development of lateral line placodes: taking a broader view.
AB  - The lateral line system of anamniote vertebrates enables the detection of local
      water movement and weak bioelectric fields. Ancestrally, it comprises neuromasts 
      small sense organs containing mechanosensory hair cells - distributed in
      characteristic lines over the head and trunk, flanked on the head by fields of
      electroreceptive ampullary organs, innervated by afferent neurons projecting
      respectively to the medial and dorsal octavolateral nuclei in the hindbrain.
      Given the independent loss of the electrosensory system in multiple lineages, the
      development and evolution of the mechanosensory and electrosensory components of
      the lateral line must be dissociable. Nevertheless, the entire system arises from
      a series of cranial lateral line placodes, which exhibit two modes of sensory
      organ formation: elongation to form sensory ridges that fragment (with neuromasts
      differentiating in the center of the ridge, and ampullary organs on the flanks),
      or migration as collectives of cells, depositing sense organs in their wake.
      Intensive study of the migrating posterior lateral line placode in zebrafish has
      yielded a wealth of information concerning the molecular control of migration and
      neuromast formation in this migrating placode, in this cypriniform teleost
      species. However, our mechanistic understanding of neuromast and ampullary organ
      formation by elongating lateral line placodes, and even of other zebrafish
      lateral line placodes, is sparse or non-existent. Here, we attempt to highlight
      the diversity of lateral line development and the limits of the current research
      focus on the zebrafish posterior lateral line placode. We hope this will
      stimulate a broader approach to this fascinating sensory system. 

PMID- 24582731
TI  - Exposure to p,p'-dichlorodiphenyldichloroethylene (DDE) induces fasting
      hyperglycemia without insulin resistance in male C57BL/6H mice.
AB  - Approximately 8.3% of the United States (U.S.) population have either diagnosed
      or undiagnosed diabetes mellitus. Out of all the cases of diabetes mellitus,
      approximately 90-95% of these cases are type 2 diabetes mellitus (T2D). Although
      the exact cause of T2D remains elusive, predisposing factors include age, weight,
      poor diet, and a sedentary lifestyle. Until recently the association between
      exposure to environmental contaminants and the occurrence of diabetes had been
      unexplored. However, recent epidemiological studies have revealed that elevated
      serum concentrations of certain persistent organic pollutants (POPs), especially
      organochlorine pesticides, are positively associated with increased prevalence of
      T2D and insulin resistance. The current study seeks to investigate if this
      association is causative or coincidental. Male C57BL/6H mice were exposed to DDE
      (2.0mg/kg or 0.4mg/kg) or vehicle (corn oil; 1mL/kg) for 5 days via oral gavage;
      fasting blood glucose, glucose tolerance, and insulin challenge tests were
      performed following a 7 day resting period. Exposure to DDE caused significant
      hyperglycemia compared to vehicle and this hyperglycemic effect persisted for up
      to 21 days following cessation of DDE administration. Intraperitoneal glucose
      tolerance tests and phosphorylation of Akt in the liver, skeletal muscle, and
      adipose tissue following insulin challenge were comparable between vehicle and
      DDE treated animals. To determine the direct effect of exposure to DDE on glucose
      uptake, in vitro glucose uptake assays following DDE exposure were performed in
      L6 myotubules and 3T3-L1 adipocytes. In summary, subacute exposure to DDE does
      produce fasting hyperglycemia, but this fasting hyperglycemia does not appear to
      be mediated by insulin resistance. Thus, the current study reveals that subacute
      exposure to DDE does alter systemic glucose homeostasis and may be a contributing
      factor to the development of hyperglycemia associated with diabetes. 

PMID- 24582733
TI  - The pain and movement reasoning model: introduction to a simple tool for
      integrated pain assessment.
AB  - Pain is no longer considered to be simply the transmission of nociception, but
      rather an output subsequent to the complex interactions of homeostatic systems.
      Manual therapists' clinical reasoning needs to incorporate this complexity in
      order to develop individualised effective treatment plans. Pain classification
      strategies attempting to assist clinical reasoning traditionally define multiple
      types of pain - nociceptive, neuropathic, centrally sensitised - potentially
      fitting elements of the pain experience to linear independent systems, rather
      than embracing the multiple dimensions. It is our contention that pain should not
      be classified unidimensionally. In all pain states consideration should be given
      to the combined influence of physiological, cognitive, emotional and social
      inputs, all of which have the potential to influence nociception. The Pain and
      Movement Reasoning Model presented in this paper attempts to capture the
      complexity of the human pain experience by integrating these multiple dimensions
      into a decision making process. Three categories have been created to facilitate
      this - central modulation, regional influences, and local stimulation. The Model
      allows for the identification of a predominant element to become the focus of
      treatment but also for the identification of changes to clinical presentation,
      where new treatment targets can emerge. 

PMID- 24582734
TI  - Epidemiology of toxoplasmosis in white tailed deer (Odocoileus virginianus):
      occurrence, congenital transmission, correlates of infection, isolation, and
      genetic characterization of Toxoplasma gondii.
AB  - The prevalence of Toxoplasma gondii in white tailed deer (WTD) in the USA is high
      but little is known of the epidemiology of toxoplasmosis in this host. In the
      present study, we compared T. gondii seroprevalence from 749 WTD collected in
      2012 and 2013 from a Metropolitan Park in Ohio and 487 WTD deer shot in Minnesota
      during 2008, 2009, and 2010. Serum samples were tested for antibodies to T.
      gondii by the modified agglutination test (cut-off titer, 25). Additionally
      myocardial samples from 123 seropositive WTD from Ohio were digested in pepsin
      and the digests were bioassayed for the isolation of T. gondii. Furthermore, to
      estimate transplacental rate of transmission, brains from 155 fetuses (included
      twins) from 148 deer from Minnesota were bioassayed in mice for the isolation of
      viable T. gondii. Seroprevalence of T. gondii varied with the year of collection,
      geography, and the age of deer. Of the Ohio deer sampled in 2012 and 2013
      seroprevalences for the two years were similar (73.4% and 75.7%, respectively);
      remarkably 150 (66.1%) of 227 deer of <1 year of age were seropositive. Of the
      Minnesota deer, seroprevalence was lowest for the year 2008 (14.8%, 26/175)
      versus 2009 (27.7%, 59/213), and 2010 (25.2%, 25/99), thought to be related to
      environmental temperatures. Viable T. gondii was isolated in mice from the
      myocardium of four WTD from Ohio, and brain of one WTD fetus from Minnesota.
      Tachyzoites from infected mouse tissues were further propagated in cell culture.
      The DNA isolated from culture-derived tachyzoites of these five T. gondii
      isolates was characterized using 11 PCR-RFLP markers (SAG1, 5'- and 3'-SAG2,
      alt.SAG2, SAG3, BTUB, GRA6, c22-8, c29-2, L358, PK1 and Apico). Four genotypes
      were found, including ToxoDB genotype no. 1 (Type II), no. 2 (Type III), no. 3
      (Type II variant) and no. 146. Results indicate fluctuating seroprevalence,
      probably related to weather and warrant further epidemiological studies. 

PMID- 24582735
TI  - Evaluation of health status of horses immunized with snake venom and montanide
      adjuvants, IMS 3012 (nanoparticle), ISA 206 and ISA 35 (emulsion based) during
      polyvalent snake antivenom production: hematological and biochemical assessment.
AB  - Several biochemical and hematological changes in horses are observed during
      production of snake antivenom. Although conventional adjuvants like Freund's
      (Complete and Incomplete) are good immunopotentiators, they produce considerable
      local reactions in animals. Variety of commercial adjuvants, like montanide
      adjuvants, having high immunopotentiation and showing lesser side effects are
      available. The prime objective during antivenom production is to strike a balance
      between safety of immunized horses and efficacy of the product. In our earlier
      work, efficacy of montanide group of adjuvants in antivenom production has
      already been established. The aim of the present work was to assess the safety
      parameters in horses, viz.: biochemical and hematological, during production of
      snake antivenom. In the present study, 33 new horses were randomly divided into
      four groups and hyperimmunized using mixture of snake venoms, viz.: Cobra venom,
      Russell's viper venom, Krait venom and Echis venom along with montanide
      adjuvants, IMS 3012, ISA 206, ISA 35 and Incomplete Freund's adjuvant as a
      control adjuvant; through subcutaneous route at intervals of two weeks. During
      the immunization period, biochemical and hematological parameters were monitored
      at 0th, 14th, 21st, 30th and 42nd weeks. The mean hemoglobin values dropped
      slightly during initial immunization but subsequently regained to normal levels.
      The mean serum total protein values and globulin levels showed an increment in
      all the four groups, compared to day zero, vice-versa a slight drop was observed
      in albumin levels. No significant changes were observed in serum creatinine,
      bilirubin, alkaline phosphatase and blood urea nitrogen values. Finally, we
      conclude that montanide adjuvants could be a safer alternative to the
      conventional adjuvants for primary phase of immunization in antivenom production.

PMID- 24582736
TI  - Molecular data do not provide unambiguous support for the monophyly of flatfishes
      (Pleuronectiformes): a reply to Betancur-R and Orti.
AB  - Betancur-R and Orti (2014) offer a criticism of our recent examination of the
      monophyly of extant flatfishes (Pleuronectiformes; Campbell et al., 2013). We
      welcome this opportunity to examine and respond to the main issues presented in
      Betancur-R and Orti (2014). Briefly, this debate centers on the question of
      whether or not analyses of the available evidence support a stable and confident
      conclusion regarding a sister group relationship between the two recognized
      pleuronectiform suborders: Psettodoidei (four species) and Pleuronectoidei (>700
      species). In Campbell et al. (2013), we reported results based on sequences from
      six nuclear genes compatible with monophyly of Pleuronectoidei but not with that
      of Pleuronectiformes. In our analyses, the most closely related percomorph family
      to the Pleuronectoidei was resolved to be the Centropomidae. In Campbell et al.
      (2013), we also provided a critical review of the morphological evidence in favor
      flatfish monophyly showing that this evidence requires a careful re-examination
      where it concerns psettodoids. Here we present our perspective on the issues
      raised in Betancur-R and Orti (2014). 

PMID- 24582737
TI  - Identification of naturally occurring hybrids between two overexploited sciaenid
      species along the South African coast.
AB  - Hybridisation between fish species can play a significant role in evolutionary
      processes and can influence management and conservation planning, however, this
      phenomenon has been widely understudied, especially in marine organisms. The
      distribution limits of two sciaenid species (silver kob, Argyrosomus inodorus,
      and dusky kob, A. japonicus) partly overlap along the South African coast, where
      both species have undergone severe depletion due to overfishing. Following the
      identification of a number of possible cases of species misidentification or
      hybridisation (21 out of 422 individuals), nuclear and mitochondrial DNA data
      (12microsatellite loci and 562bp of the COI gene) were analysed to investigate
      the genetic composition of these individuals. Results indicated a field-based
      species misidentification rate of approximately 2.8% and a rate of natural
      hybridisation of 0.7%. Interestingly, all hybrid fish resulted from first
      generation (F1) hybridisation events, which occurred exclusively between silver
      kob females and dusky kob males. Whether hybridisation is the result of natural
      events (such as secondary contact following a shift in distribution range), or
      anthropogenic activities (size-selective pressure due to overfishing), these
      findings have important implications for critical recovery and future management
      of these species in the wild. 

PMID- 24582738
TI  - Frequency of Chlamydia trachomatis-specific T cell interferon-gamma and
      interleukin-17 responses in CD4-enriched peripheral blood mononuclear cells of
      sexually active adolescent females.
AB  - An evaluation of CD4 T cell responses to candidate Chlamydia trachomatis vaccine
      antigens was conducted in an adolescent female cohort exposed through natural
      infection to explore antigen immunogenicity and correlation with protection from
      reinfection. The frequency of peripheral blood CD4 T cell IFN-gamma and IL-17
      responses to three candidate vaccine antigens, polymorphic membrane protein G
      (PmpG), F (PmpF), and major outer membrane protein (MOMP), were determined by
      ELISPOT; responses to chlamydial heat shock protein 60 (HSP60) and to elementary
      bodies (EB) were included for comparison. Responses of Infected (n=8),
      Seropositive/Uninfected (n=13), and Seronegative/Uninfected (n=18) participants
      were compared. The median CD4 IFN-gamma response to EB was significantly
      increased in Infected (P=0.003) and Seropositive/Uninfected (P=0.002) versus
      Seronegative/Uninfected female subjects. Higher rates of positive IFN-gamma
      responders to EB, PmpF, and MOMP were detected in Seropositive/Uninfected versus
      Seronegative/Uninfected participants (P=0.021). IL-17 responses were generally
      low. A positive IFN-gamma response to any of the antigens tested was associated
      with a trend toward a reduced risk of reinfection, although not statistically
      significant. Among this adolescent cohort, chlamydial-specific CD4 IFN-gamma but
      not IL-17 responses were detected in acutely and previously infected participants
      and a positive CD4 IFN-gamma response was associated with a non-significant
      reduced risk of reinfection. 

PMID- 24582739
TI  - Dose dependent neuroprotection of the noble gas argon after cardiac arrest in
      rats is not mediated by K(ATP)-channel opening.
AB  - PURPOSE: Argon at a dosage of 70% is neuroprotective when given 1 h after cardiac
      arrest (CA) in rats. In a rodent model, we investigated if the neuroprotective
      effects of argon are dose dependent and mediated by adenosine triphosphate
      dependent potassium (K(ATP)) channels. METHODS: Forty-seven male Sprague-Dawley
      rats were subjected to 7 min of CA and 3 min of cardiopulmonary resuscitation
      (CPR). In protocol I animals were randomized to receive either 70% or 40% argon
      ventilation 1 h after successful CPR or no argon-treatment. Animals of the second
      protocol also received 1 h of 70% argon ventilation or no argon treatment but
      were randomized to a group receiving the K(ATP) channel blocker 5
      hydroxydecanoate (5-HD). For all animals a neurological deficit score (NDS) was
      calculated daily for seven days following the experiment before the animals were
      killed and the brains harvested for histopathological analyses. RESULTS: All
      animals survived. Control animals exhibited severe neurologic dysfunction at all
      points in time as measured with the NDS. Argon treated animals showed significant
      improvements in the NDS through all postoperative days in a dose dependent
      fashion. This was paralleled by a significant reduction in the neuronal damage
      index in the neocortex and the hippocampal CA 3/4 region. Administration of 5-HD
      neither abolished the positive effects on functional recovery nor on
      histopathologic changes observed in the argon group. CONCLUSION: Our study
      demonstrates a dose dependent neuroprotective effect of argon administration in
      this rodent model, which is not mediated via ATP dependent potassium channels.

PMID- 24582740
TI  - Trends in the incidence of presumed cardiac out-of-hospital cardiac arrest in
      Perth, Western Australia, 1997-2010.
AB  - AIM: This study investigated temporal trends in the incidence of out-of-hospital
      cardiac arrests (OHCA) in metropolitan Perth (Western Australia) between 1997 and
      2010. METHODS: We calculated crude and age-and-sex-standardised incidence rates
      (ASIRs) using the 2011 Australian population as the standard population.
      Incidence rates are reported per 100,000 population, and for eight age categories
      (0-14, 15-34, 35-64, 65-69, 70-74, 75-79, 80-84, >=85). Temporal trends were
      analysed with linear regression. RESULTS: Over the 14-years, 12,421 OHCAs of
      presumed cardiac aetiology were attended by St John Ambulance Western Australia
      paramedics. The overall ASIR per 100,000 population decreased significantly over
      this time (75.7-70.6, p<0.001), but predominantly between 1997 and 2002 (75.7
      65.9) and in those aged >=65 years (410.2-336.7, p<0.001). This trend was
      observed for both males and females and across all five-year age-groups between
      65 and 84 years, but not in those >=85 years--whom by 2010 represented 30% of the
      older adult (65+ years) OHCAs attended, up from 16% in 1997 (p<0.001).
      CONCLUSIONS: Over the study period, a decline in the ASIR for OHCAs of presumed
      cardiac aetiology in Perth was observed. This is largely attributed to a
      decreasing incidence in the population aged 65-84 years between 1997 and 2002,
      and is likely the result of improvements in cardiovascular risk profiles that
      have previously been reported among Western Australian adults. Future studies of
      the impact of the ageing population are required.

PMID- 24582741
TI  - Controlling ventilation during cardiopulmonary resuscitation.

PMID- 24582742
TI  - Reply to letter: Controlling ventilation during cardiopulmonary resuscitation.

PMID- 24582743
TI  - False positive absent somatosensory evoked potentials in cardiac arrest with
      therapeutic hypothermia.

PMID- 24582744
TI  - Special issue of the second biennial meeting of the North American Society for
      Comparative Endocrinology (Sociedad Norteamericana de Endocrinologia Comparada;
      Societe Nord-Americaine d'Endocrinologie Comparee).

PMID- 24582745
TI  - Crystal structure of a "loopless" GH19 chitinase in complex with chitin
      tetrasaccharide spanning the catalytic center.
AB  - DESCRIPTIONS: The structure of a GH19 chitinase from the moss Bryum coronatum
      (BcChi-A) in complex with the substrate was examined by X-ray crystallography and
      NMR spectroscopy in solution. The X-ray crystal structure of the inactive mutant
      of BcChi-A (BcChi-A-E61A) liganded with chitin tetramer (GlcNAc)4 revealed a
      clear electron density of the tetramer bound to subsites -2, -1, +1, and +2.
      Individual sugar residues were recognized by several amino acids at these
      subsites through a number of hydrogen bonds. This is the first crystal structure
      of GH19 chitinase liganded with oligosaccharide spanning the catalytic center.
      NMR titration experiments of chitin oligosaccharides into the BcChi-A-E61A
      solution showed that the binding mode observed in the crystal structure is
      similar to that in solution. The C-1 carbon of -1 GlcNAc, the Oepsilon1 atom of
      the catalytic base (Glu70), and the Ogamma atom of Ser102 form a "triangle"
      surrounding the catalytic water, and the arrangement structurally validated the
      proposed catalytic mechanism of GH19 chitinases. The glycosidic linkage between 
      1 and +1 sugars was found to be twisted and under strain. This situation may
      contribute to the reduction of activation energy for hydrolysis. The complex
      structure revealed a more refined mechanism of the chitinase catalysis.

PMID- 24582746
TI  - Overexpressed homeobox B9 regulates oncogenic activities by transforming growth
      factor-beta1 in gliomas.
AB  - Glioma is the leading cause of deaths related to tumors in the central nervous
      system. The mechanisms of gliomagenesis remain elusive to date. Homeobox B9
      (HOXB9) has a crucial function in the regulation of gene expression and cell
      survival, but its functions in glioma formation and development have yet to be
      elucidated. This study showed that HOXB9 expression in glioma tissues was
      significantly higher than that in nontumor tissues. Higher HOXB9 expression was
      also significantly associated with advanced clinical stage in glioma patients.
      HOXB9 overexpression stimulated the proliferation, migration, and sphere
      formation of glioma cells, whereas HOXB9 knockdown elicited an opposite effect.
      HOXB9 overexpression also increased the tumorigenicity of glioma cells in vivo.
      Moreover, the activation of transforming growth factor-beta1 contributed to HOXB9
      induced oncogenic activities. HOXB9 could be used as a predictable biomarker to
      be detected in different pathological and histological subtypes in glioma for
      diagnosis or prognosis. 

PMID- 24582747
TI  - LC3B is indispensable for selective autophagy of p62 but not basal autophagy.
AB  - Autophagy is a unique intracellular protein degradation system accompanied by
      autophagosome formation. Besides its important role through bulk degradation in
      supplying nutrients, this system has an ability to degrade certain proteins,
      organelles, and invading bacteria selectively to maintain cellular homeostasis.
      In yeasts, Atg8p plays key roles in both autophagosome formation and selective
      autophagy based on its membrane fusion property and interaction with autophagy
      adaptors/specific substrates. In contrast to the single Atg8p in yeast, mammals
      have 6 homologs of Atg8p comprising LC3 and GABARAP families. However, it is not
      clear these two families have different or similar functions. The aim of this
      study was to determine the separate roles of LC3 and GABARAP families in
      basal/constitutive and/or selective autophagy. While the combined knockdown of
      LC3 and GABARAP families caused a defect in long-lived protein degradation
      through lysosomes, knockdown of each had no effect on the degradation. Meanwhile,
      knockdown of LC3B but not GABARAPs resulted in significant accumulation of
      p62/Sqstm1, one of the selective substrate for autophagy. Our results suggest
      that while mammalian Atg8 homologs are functionally redundant with regard to
      autophagosome formation, selective autophagy is regulated by specific Atg8
      homologs.

PMID- 24582748
TI  - Atorvastatin attenuates myocardial remodeling induced by chronic intermittent
      hypoxia in rats: partly involvement of TLR-4/MYD88 pathway.
AB  - Inflammatory processes and oxidative stress are known to play a key role in the
      development of cardiovascular complications such as cardiac hypertrophy induced
      by chronic intermittent hypoxia (CIH), the most characteristic pathophysiological
      change of obstructive sleep apnea syndrome (OSAS). Current evidence suggests that
      competitive inhibitors of 3-hydroxy-3-methylglutaryl-CoA coenzyme A reductase,
      such as atorvastatin, not only reduce blood lipids but also have anti
      inflammatory and inhibit oxidative stress benefits. This study examined the
      protective role of atorvastatin in CIH-induced cardiac hypertrophy. Adult male
      wistar rats were subjected to 8h of intermittent hypoxia/day, with/without
      atorvastatin for 6 weeks. Ventricular remodeling, toll-like receptor 4 (TLR-4),
      myeloid differentiation primary response protein 88 (MYD88), inflammatory agents
      and radical oxygen species were determined. As a result, we found that treatment
      with atorvastatin markedly inhibited the mRNA and protein expressions of TLR4,
      MYD88 and the downstream inflammatory agents and radical oxygen species.
      Administration of atorvastatin following CIH significantly ameliorated the
      myocardial injury, such as cardiac hypertrophy. In conclusion, Pre-CIH
      atorvastatin administration may attenuate TLR-4/MYD88 mediated inflammatory
      processes and oxidative stress in the injured rat myocardium, and this may be one
      mechanism by which atorvastatin ameliorated myocardial injury following CIH.

PMID- 24582749
TI  - miR-138-5p reverses gefitinib resistance in non-small cell lung cancer cells via
      negatively regulating G protein-coupled receptor 124.
AB  - Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) such as
      gefitinib are clinically effective treatments for non-small cell lung cancer
      (NSCLC) patients with EGFR activating mutations. However, therapeutic effect is
      ultimately limited by the development of acquired TKI resistance. MicroRNAs
      (miRNAs) represent a category of small non-coding RNAs commonly deregulated in
      human malignancies. The aim of this study was to investigate the role of miRNAs
      in gefitinib resistance. We established a gefitinib-resistant cell model (PC9GR)
      by continually exposing PC9 NSCLC cells to gefitinib for 6 months. MiRNA
      microarray screening revealed miR-138-5p showed the greatest downregulation in
      PC9GR cells. Re-expression of miR-138-5p was sufficient to sensitize PC9GR cells
      and another gefitinib-resistant NSCLC cell line, H1975, to gefitinib.
      Bioinformatics analysis and luciferase reporter assay showed that G protein
      coupled receptor124 (GPR124) was a direct target of miR-138-5p. Experimental
      validation demonstrated that expression of GPR124 was suppressed by miR-138-5p on
      protein and mRNA levels in NSCLC cells. Furthermore, we observed an inverse
      correlation between the expression of miR-138-5p and GPR124 in lung
      adenocarcinoma specimens. Knockdown of GPR124 mimicked the effects of miR-138-5p
      on the sensitivity to gefitinib. Collectively, our results suggest that
      downregulation of miR-138-5p contributes to gefitinib resistance and that
      restoration of miR-138-5p or inhibition GPR124 might serve as potential
      therapeutic approach for overcoming NSCLC gefitinib resistance.

PMID- 24582750
TI  - Identification of a cDNA encoding a novel small secretory protein, neurosecretory
      protein GL, in the chicken hypothalamic infundibulum.
AB  - To find novel neuropeptide and/or peptide hormone precursors in the avian brain,
      we performed a cDNA subtractive screen of the chicken hypothalamic infundibulum,
      which contains one of the feeding and neuroendocrine centers. After sequencing
      596 clones, we identified a novel cDNA encoding a previously unknown protein. The
      deduced precursor protein consisted of 182 amino acid residues, including one
      putative small secretory protein of 80 amino acid residues. This small protein
      was flanked at the N-terminus by a signal peptide and at the C-terminus by a
      glycine amidation signal and a dibasic amino acid cleavage site. Because the
      predicted C-terminal amino acids of the small protein were Gly-Leu-NH2, the small
      protein was named neurosecretory protein GL (NPGL). Quantitative RT-PCR analysis
      demonstrated specific expression of the NPGL precursor mRNA in the hypothalamic
      infundibulum. Furthermore, the mRNA levels in the hypothalamic infundibulum
      increased during post-hatching development. In situ hybridization analysis showed
      that the cells containing the NPGL precursor mRNA were localized in the medial
      mammillary nucleus and infundibular nucleus within the hypothalamic infundibulum
      of 8- and 15-day-old chicks. Subcutaneous infusion of NPGL in chicks increased
      body weight gain without affecting food intake. To our knowledge, this is the
      first report to describe the identification and localization of the NPGL
      precursor mRNA and the function of its translated product in animals. Our
      findings indicate that NPGL may participate in the growth process in chicks. 

PMID- 24582751
TI  - Antibiotic drug tigecycline inhibited cell proliferation and induced autophagy in
      gastric cancer cells.
AB  - Tigecycline acts as a glycylcycline class bacteriostatic agent, and actively
      resists a series of bacteria, specifically drug fast bacteria. However,
      accumulating evidence showed that tetracycline and their derivatives such as
      doxycycline and minocycline have anti-cancer properties, which are out of their
      broader antimicrobial activity. We found that tigecycline dramatically inhibited
      gastric cancer cell proliferation and provided an evidence that tigecycline
      induced autophagy but not apoptosis in human gastric cancer cells. Further
      experiments demonstrated that AMPK pathway was activated accompanied with the
      suppression of its downstream targets including mTOR and p70S6K, and ultimately
      induced cell autophagy and inhibited cell growth. So our data suggested that
      tigecycline might act as a candidate agent for pre-clinical evaluation in
      treatment of patients suffering from gastric cancer. 

PMID- 24582752
TI  - Structural and biochemical study of Bacillus subtilis HmoB in complex with heme.
AB  - Most bacteria have developed a hemoprotein degradation system to acquire iron
      from their hosts. Bacillus subtilis HmoB, a heme monooxygenase, is involved in
      the degradation of heme and subsequent release of iron. HmoB contains a C
      terminal ABM domain, which is similar in sequence and structure to other heme
      monooxygenases. Heme degradation assay showed that highly conserved residues
      (N70, W128, and H138) near the heme-binding site were critical for activity of
      HmoB. However, HmoB was shown to be different from other bacterial heme
      oxygenases due to its longer N-terminal region and formation of a biological
      monomer instead of a dimer. The degradation product of B. subtilis HmoB was
      identified as staphylobilin from mass spectrometric analysis of the product and
      release of formaldehyde during degradation reaction. 

PMID- 24582753
TI  - Over-expression of FoxM1 is associated with adverse prognosis and FLT3-ITD in
      acute myeloid leukemia.
AB  - Forkhead box M1 (FoxM1) drives cell cycle progression and the prevention of
      growth arrest and is over-expressed in many human malignancies. However, the
      characteristics of FoxM1 in acute myeloid leukemia (AML) are not clearly
      understood. We investigated the expression level of FoxM1 and analyzed the
      correlation of FoxM1 expression with AML patient characteristics and prognoses.
      Changes in FoxM1 expression were detected after MV4-11 cells, which have an
      internal tandem duplication (ITD) of the fms-like tyrosine kinase 3 gene (FLT3
      ITD), and control THP1 cells (encoding wild-type FLT3) were treated with the FLT3
      receptor tyrosine kinase inhibitor AC220 (quizartinib) or FLT3 ligand (FL).
      Finally, we determined the apoptosis rates after the addition of the FoxM1
      inhibitor thiostrepton (TST) to AML cells with or without FLT3-ITD. The
      expression of FoxM1 in AML patients was correlated with the presence of FLT3-ITD,
      genetic groups, and possibly overall survival. Inhibition of FLT3-ITD by AC220
      down-regulated FoxM1 expression in MV4-11 cells, and stimulation of FLT3 by FL up
      regulated FoxM1 expression in MV4-11 and THP1 cells. TST induced the apoptosis of
      MV4-11 and THP1 cells in a dose-dependent manner. Thus, FoxM1 is a potential
      prognostic marker and a promising therapeutic target in AML. 

PMID- 24582754
TI  - Immediately loaded mini dental implants as overdenture retainers: 1-Year cohort
      study of implant stability and peri-implant marginal bone level.
AB  - AIM: This 1-year cohort study investigated stability and peri-implant marginal
      bone level of immediately loaded mini dental implants used to retain
      overdentures. MATERIALS AND METHODS: Each of 30 edentulous patients received 4
      mini dental implants (1.8 mm * 13 mm) in the interforaminal mandibular region.
      The implants were immediately loaded with pre-made overdentures. Outcome measures
      included implant stability and bone resorption. Implant stability was measured
      using the Periotest Classic((r)) device immediately after placement and on the
      3rd and 6th weeks and the 4th, 6th and 12th months postoperatively. The peri
      implant marginal bone level (PIBL) was evaluated at the implant's mesial and
      distal sides from the polished platform to the marginal crest. Radiographs were
      taken using a tailored film holder to reproducibly position the X-ray tube at the
      6th week, 4th and 12th months postoperatively. RESULTS: The primary stability
      (Periotest value, PTV) measured -0.27 +/- 3.41 on a scale of -8 to + 50 (lower
      PTV reflects higher stability). The secondary stability decreased significantly
      until week 6 (mean PTV = 7.61 +/- 7.05) then increased significantly reaching
      (PTV = 6.17 +/- 6.15) at 12 months. The mean PIBL measured -0.40 mm after 1 year
      of functional loading, with no statistically significant differences at the
      various follow-ups (p = 0.218). CONCLUSIONS: Mini dental implants placed into the
      interforaminal region could achieve a favorable primary stability for immediate
      loading. The follow-up Periotest values fluctuated, apparently reflecting the
      dynamics of bone remodeling, with the implants remaining clinically stable
      (98.3%) after 1 year of function. The 1-year bone resorption around immediately
      loaded MDIs is within the clinically acceptable range for standard implants.

PMID- 24582755
TI  - Response of human skin to esthetic scarification.
AB  - This study was undertaken to investigate changes in RNA expression in previously
      healthy adult human skin following thermal injury induced by contact with hot
      metal that was undertaken as part of esthetic scarification, a body modification
      practice. Subjects were recruited to have pre-injury skin and serial wound
      biopsies performed. 4 mm punch biopsies were taken prior to branding and 1 h, 1
      week, and 1, 2 and 3 months after injury. RNA was extracted and quality assured
      prior to the use of a whole-genome based bead array platform to describe
      expression changes in the samples using the pre-injury skin as a comparator.
      Analysis of the array data was performed using k-means clustering and a
      hypergeometric probability distribution without replacement and corrections for
      multiple comparisons were done. Confirmatory q-PCR was performed. Using a k of
      10, several clusters of genes were shown to co-cluster together based on Gene
      Ontology classification with probabilities unlikely to occur by chance alone. OF
      particular interest were clusters relating to cell cycle, proteinaceous
      extracellular matrix and keratinization. Given the consistent expression changes
      at 1 week following injury in the cell cycle cluster, there is an opportunity to
      intervene early following burn injury to influence scar development.

PMID- 24582756
TI  - Predictors of health status and health-related quality of life 12 months after
      severe burn.
AB  - INTRODUCTION: Sustaining a moderate to severe burn injury is associated with the
      potential for substantial impairments to long-term physical and psychosocial
      health, including health related quality of life (HRQoL). The objective of this
      study was to identify clinical and patient characteristics which predict HRQoL 12
      months after injury. METHODS: A total of 125 patients were recruited over the
      study period, although only 99 were included in the final analysis representing
      all those who completed both the pre-burn and 12-months after burn injury Short
      Form 36 Medical Outcomes Survey (SF-36v2). These patients also completed the Burn
      Specific Health Scale-Brief (BSHS-B). Patient demographics and burn injury
      characteristics and treatment factors were collected to identify which factors
      predict 12-month health status outcomes. Multiple linear regression analyses were
      conducted to identify important predictors of outcomes. The SF36v2 models were
      adjusted for pre-injury measurements. RESULTS: Older age (regression coefficient 
      0.26, 95% confidence interval (95% CI) -0.38, -0.13), female gender (-8.08, 95%
      CI -12.8, -3.34) and increased percentage of full-thickness burns per body
      surface area (-0.51; 95% CI -0.88, -0.13) were important predictors of poorer
      physical health status at 12 months. Older age (-0.15, 95% CI -0.26, -0.04) and
      increased percentage of full-thickness burns per body surface area (-0.36, 95% CI
      -0.69, -0.03) were important predictors of poorer mental health status at 12
      months. Older age (-0.38; 95%CI -0.66, -0.11) and female gender (-12.17; 95% CI 
      22.76, -1.57) were important predictors of poorer BSHS-B total score at 12 months
      after injury. CONCLUSIONS: Given the complexity of burn care rehabilitation,
      physical and psychosocial screening and assessment within the first weeks after a
      burn injury along with adequate monitoring after discharge should be undertaken
      in burn injured patients. In this context, patients of specific demographics,
      such as female patients and older patients, and patients with a higher percentage
      of full thickness surface area burns are of greater risk for poorer physical and
      psychological outcomes and may benefit from additional monitoring and
      rehabilitation.

PMID- 24582757
TI  - Implementing Toxicity Testing in the 21st Century (TT21C): Making safety
      decisions using toxicity pathways, and progress in a prototype risk assessment.
AB  - Risk assessment methodologies in toxicology have remained largely unchanged for
      decades. The default approach uses high dose animal studies, together with human
      exposure estimates, and conservative assessment (uncertainty) factors or linear
      extrapolations to determine whether a specific chemical exposure is 'safe' or
      'unsafe'. Although some incremental changes have appeared over the years, results
      from all new approaches are still judged against this process of extrapolating
      high-dose effects in animals to low-dose exposures in humans. The US National
      Research Council blueprint for change, entitled Toxicity Testing in the 21st
      Century: A Vision and Strategy called for a transformation of toxicity testing
      from a system based on high-dose studies in laboratory animals to one founded
      primarily on in vitro methods that evaluate changes in normal cellular signalling
      pathways using human-relevant cells or tissues. More recently, this concept of
      pathways-based approaches to risk assessment has been expanded by the description
      of 'Adverse Outcome Pathways' (AOPs). The question, however, has been how to
      translate this AOP/TT21C vision into the practical tools that will be useful to
      those expected to make safety decisions. We have sought to provide a practical
      example of how the TT21C vision can be implemented to facilitate a safety
      assessment for a commercial chemical without the use of animal testing. To this
      end, the key elements of the TT21C vision have been broken down to a set of
      actions that can be brought together to achieve such a safety assessment. Such
      components of a pathways-based risk assessment have been widely discussed,
      however to-date, no worked examples of the entire risk assessment process exist.
      In order to begin to test the process, we have taken the approach of examining a
      prototype toxicity pathway (DNA damage responses mediated by the p53 network) and
      constructing a strategy for the development of a pathway based risk assessment
      for a specific chemical in a case study mode. This contribution represents a
      'work-in-progress' and is meant to both highlight concepts that are well
      developed and identify aspects of the overall process which require additional
      development. To guide our understanding of what a pathways-based risk assessment
      could look like in practice, we chose to work on a case study chemical
      (quercetin) with a defined human exposure and to bring a multidisciplinary team
      of chemists, biologists, modellers and risk assessors to work together towards a
      safety assessment. Our goal was to see if the in vitro dose response for
      quercetin could be sufficiently understood to construct a TT21C risk assessment
      without recourse to rodent carcinogenicity study data. The data presented include
      high throughput pathway biomarkers (p-H2AX, p-ATM, p-ATR, p-Chk2, p53, p-p53,
      MDM2 and Wip1) and markers of cell-cycle, apoptosis and micronuclei formation,
      plus gene transcription in HT1080 cells. Eighteen point dose response curves were
      generated using flow cytometry and imaging to determine the concentrations that
      resulted in significant perturbation. NOELs and BMDs were compared to the output
      from biokinetic modelling and the potential for in vitro to in vivo extrapolation
      explored. A first tier risk assessment was performed comparing the total
      quercetin concentration in the in vitro systems with the predicted total
      quercetin concentration in plasma and tissues. The shortcomings of this approach
      and recommendations for improvement are described. This paper therefore describes
      the current progress in an ongoing research effort aimed at providing a pathways
      based, proof-of-concept in vitro-only safety assessment for a consumer use
      product. 

PMID- 24582758
TI  - Association between the hemodialysis eating index and risk factors of
      cardiovascular disease in hemodialysis patients.
AB  - OBJECTIVE: In this study, a Hemodialysis Eating Index (HDEI) suitable for
      hemodialysis (HD) patients in Taiwan was developed based on the dietary
      recommendations of the U.S. National Kidney Foundation for HD patients and the
      Taiwanese 2011 Daily Food Guide. The HDEI was used to explore HD-associated
      cardiovascular disease (CVD) risk factors. METHODS: In this prospective study,
      108 HD patients from 2 HD centers in Taiwan were recruited as participants in
      2010. All participants were older than 20 years. Patient CVD risk factor and 3
      day dietary data were collected, and their HDEI scores were calculated. The HDEI
      scores comprise 12 food-related factors: the consumption of vegetables, fruits,
      total grains, whole grains, high-protein foods, high biological values, red and
      white meat, fish, oils, saturated fatty acids or trans fatty acids, nuts, and the
      duration of multivitamin use. The scores ranged from 5 to 100, and SAS software
      version 9.3 was used to perform statistical analyses. A P value less than .05 was
      considered statistically significant. RESULTS: The HDEI scores and serum albumin
      (Alb) levels were significantly and positively correlated. The participants were
      divided into 2 groups on the basis of the median HDEI score of 72.2. Two months
      after HDEI evaluation, the high-HDEI scoring group exhibited significantly
      decreased levels of serum total cholesterol and increased hemoglobin (Hb) levels.
      CONCLUSION: The HDEI can be used to reflect selected nutritional status markers,
      such as Alb and Hb levels and CVD risk factors, for HD patients. The HDEI can
      also serve as an eating index for HD patients in Taiwan to facilitate CVD
      prevention.

PMID- 24582759
TI  - Elevated melatonin levels in natalizumab-treated female patients with relapsing
      remitting multiple sclerosis: relationship to oxidative stress.
AB  - Natalizumab is currently the most successful clinical treatment for multiple
      sclerosis. The use of this drug is associated with the reduction in the number of
      relapses and a slowing in disease progression, as well as an improvement in signs
      and symptoms displayed by the patients. To evaluate the effect of natalizumab on
      melatonin and its relationship with peripheral oxidative damage, we studied the
      serum melatonin levels in 18 patients with relapsing-remitting multiple
      sclerosis. Natalizumab caused significant increases in serum melatonin
      concentrations. This change was associated with a rise in increase of
      antioxidants and a reduction in oxidative stress biomarkers. In conclusion, these
      data may explain, at least in part, some of the beneficial effects exhibited by
      disease antibody such as its antioxidant capacity. 

PMID- 24582760
TI  - Increase of glucocorticoids is not required for the acquisition, but hinders the
      extinction, of lithium-induced conditioned taste aversion.
AB  - Lithium chloride at doses sufficient to induce conditioned taste aversion (CTA)
      causes c-Fos expression in the paraventricular nucleus and increases the plasma
      level of corticosterone with activation of the hypothalamic-pituitary-adrenal
      axis. This study was conducted to define the role of glucocorticoid in the
      acquisition and extinction of lithium-induced CTA. In experiment 1, Sprague
      Dawley rats received dexamethasone (2mg/kg) or RU486 (20mg/kg) immediately after
      5% sucrose access, and then an intraperitoneal injection of isotonic lithium
      chloride (12ml/kg) was followed with 30min interval. Rats had either 1 or 7 days
      of recovery period before the daily sucrose drinking tests. In experiment 2, rats
      were conditioned with the sucrose-lithium pairing, and then received
      dexamethasone or vehicle at 30min before each drinking test. In experiment 3,
      adrenalectomized (ADX or ADX+B) rats were subjected to sucrose drinking tests
      after the sucrose-lithium pairing. Dexamethasone, but not RU486, pretreatment
      blunted the formation of lithium-induced CTA memory. Dexamethasone prior to each
      drinking test suppressed sucrose consumption and prolonged the extinction of
      lithium-induced CTA. Sucrose consumption was significantly suppressed not only in
      ADX+B rats but also in ADX rats during the first drinking session; however, a
      significant decrease was found only in ADX rats on the fourth drinking session.
      These results reveal that glucocorticoid is not a necessary component in the
      acquisition, but an important player in the extinction, of lithium-induced CTA,
      and suggest that a pulse increase of glucocorticoid may hinder the extinction
      memory formation of lithium-induced CTA. 

PMID- 24582761
TI  - The immunomodulatory and anti-apoptotic effect of dexamethasone in imminent
      preterm labor: an experimental study.
AB  - The study was designed to investigate the effect of dexamethasone (DEX) on the
      latency period to delivery in a murine model of preterm labor. To this purpose,
      pregnant mice were randomly assigned in groups: the control group received water
      for injection (n=20), the preterm labor group was injected with
      lipopolysaccharide (LPS) (n=22), while the glucocorticoids group was administered
      DEX either 1h before (n=17) or after (n=7) lipopolysaccharide. In a first set of
      experiments animals were monitored to record perinatal outcomes. In another set
      of experiments, the remaining animals were sacrificed eight h after
      interventions. Fetuses were homogenized to measure tumor necrosis alpha in
      supernatants. Maternal splenocytes were isolated and stimulated for cytokine
      production. Serum of mice was incubated with donor cells from healthy pregnant
      and non-pregnant animals to induce apoptosis. LPS induced preterm labor but
      treatment or pretreatment with DEX delayed parturition exerting a favorable
      impact on survival of delivered fetuses. DEX inverted the increase of
      fetoplacental tumor necrosis alpha levels. Serum of LPS-stimulated mice induced
      apoptosis of splenocytes of either pregnant or non-pregnant healthy mice; this
      was reversed after incubation of splenocytes with serum coming from DEX pre
      treated mice. The presented findings suggest that DEX administered either as pre
      treatment or treatment prolonged gestation and promoted neonatal survival in a
      sterile murine model of preterm labor. These favorable outcomes were closely
      linked to alterations in both immune and apoptotic responses of animals. 

PMID- 24582762
TI  - Thyroid hormone exacerbates vasoconstriction in insulin resistance: the role of
      ONOO(-).
AB  - Insulin resistance has been proposed to play a pivotal role in vasoconstriction
      due to increased oxidative stress. Hyperthyroidism would amplify cardiovascular
      disease risk in diabetic patients, though thyroid hormone advance vascular
      relaxation and reduce vascular contraction by virtue of NO production in vascular
      smooth muscle cells (VSMCs). Thus, we aimed to investigate the vascular tone and
      its underlying mechanism in insulin resistance accompanied by hyperthyroidism.
      Vascular reactivity studies showed that endothelium-denuded thoracic aortic rings
      from rats fed with high-fat high-sucrose (HFHS) diet and L-T4 (HFHS+L-T4)
      exhibited a stronger contractile response to noradrenaline than HFHS rats, which
      was reversed by L-NAME and GSH. Furthermore, rat thoracic aortic smooth muscle
      cells (A10) simultaneously stimulated with high glucose insulin (high Glc/Ins)
      and T3 demonstrated lower NO, superoxide anion ( [Formula: see text] ) levels,
      and higher iNOS, nitrite ( [Formula: see text] ), peroxynitrite (ONOO(-)) levels
      than that treated with T3 only. Excessive ONOO(-) markedly aggravated oxidative
      stress. Thus, we hypothesized that the elevated concentration of ONOO(-) which is
      generated by NO and [Formula: see text] could be critically instrumental in the
      progression of vasoconstriction by increasing oxidative stress. 

PMID- 24582763
TI  - [Gastrointestinal lesions and characteristics of acute gastrointestinal bleeding
      in acenocoumarol-treated patients].
AB  - In the last few years, the number of anticoagulated patients has significantly
      increased and, as a consequence, so have hemorrhagic complications due to this
      therapy. We analyzed gastrointestinal (GI) bleeding because it is the most
      frequent type of major bleeding in these patients, and we hypothesized that they
      would have lesions responsible for GI bleeding regardless of the intensity of
      anticoagulation, although excessively anticoagulated patients would have more
      serious hemorrhages. OBJECTIVES: To study the characteristics of anticoagulated
      patients with GI bleeding and the relationship between the degree of
      anticoagulation and a finding of causative lesions and bleeding severity.
      PATIENTS AND METHODS: We prospectively studied 96 patients, all anticoagulated
      with acenocoumarol and consecutively admitted to hospital between 01/01/2003 and
      09/30/2005 because of acute GI bleeding. We excluded patients with severe liver
      disease, as well as nine patients with incomplete details. RESULTS: The incidence
      of GI bleeding requiring hospitalization was 19.6 cases/100,000 inhabitants-year.
      In 90% of patients, we found a causative (85% of upper GI bleeding and 50% of
      lower GI bleeding) or potentially causative lesion, and 30% of them required
      endoscopic treatment, without differences depending on the intensity of
      anticoagulation. No relationship was found between the type of lesions observed
      and the degree of anticoagulation in these patients. Patients who received more
      intense anticoagulation therapy had more severe hemorrhages (23% of patients with
      an INR >=4 had a life-threatening bleed versus only 4% of patients with INR <4).
      CONCLUSIONS: We found an incidence of 20 severe GI bleeding episodes in
      anticoagulated patients per 100,000 inhabitants-year, with no difference in
      localization or in the frequency of causative lesions depending on the intensity
      of anticoagulation. Patients receiving more intense anticoagulation had more
      severe GI bleeding episodes.

PMID- 24582764
TI  - [Importance of diet in irritable bowel syndrome].
AB  - About two-thirds of irritable bowel syndrome (IBS) patients associate their
      symptoms with certain foods. We reviewed food-related factors putatively
      associated with manifestations of IBS. Soluble fiber may improve constipation but
      frequently increases bloating and abdominal pain. Carbohydrate malabsorption
      seems to be more frequent in IBS. A low FODMAP (fermentable oligosaccharides,
      disaccharides, monosaccharides and polyols) diet significantly reduces IBS
      symptoms and has been suggested as a therapeutic option. Serological screening
      for celiac disease should be done in patients without constipation. Moreover, non
      celiac disease gluten sensitivity, defined as gluten intolerance once celiac
      disease and wheat allergy have been ruled out, should be considered in these
      patients. There is no specific diet for IBS patients but small and frequent
      meals, avoiding greasy foods, dairy products, many carbohydrates, caffeine and
      alcohol, is recommended. 

PMID- 24582765
TI  - [Predictive value of pre-treatment hypoalbuminemia in prognosis of resected
      colorectal cancer].
AB  - INTRODUCTION: Albuminemia is part of the antitumoral systemic inflammatory
      response. We therefore analyzed its possible value in establishing the
      preoperative prognosis of colorectal carcinoma (CRC). PATIENTS AND METHODS: We
      conducted a retrospective, observational study of a series of consecutive
      patients who underwent CRC resection. Univariate and multivariate analyses of
      survival curves were performed in patients with and without pre-treatment
      hypoalbuminemia (<3.5g/dl), both in the overall group of patients and in the
      subgroup of those with pTNM stage ii tumors. In addition, we compared the 5-year
      tumor-related mortality in patients with and without hypoalbuminemia. RESULTS: A
      total of 207 patients were reviewed (median follow-up: 81 months). In the overall
      multivariate analysis, survival curves were better in patients with normal
      albumin levels than in those with hypoalbuminemia (HR=2.82; CI 95%=[1.54-5.19];
      P=.001). This better prognostic value of normal albumin levels was also
      significant in pTNM stage ii tumors: (HR=3.76; CI 95%=[1.40-10.08]; P=.009). The
      5-year mortality index was lower in patients with normal albumin levels: overall
      series=18.8% vs 42.9% (OR=3.24; CI 95%=[1.48-7.12]; p=0.001); pTNM stage ii=13.3%
      vs 44.4% (OR=5.2; CI 95%=[1.36-20.34]; P=0.004). CONCLUSIONS: Pre-treatment
      hypoalbuminemia (<3.5g/dl) was independently related to shorter survival after
      tumor resection, both in the overall series of patients and in pTNM stage ii CRC.
      If these results are confirmed, hypoalbuminemia would be a simple and significant
      marker of poor prognosis, available at the initial diagnosis.

PMID- 24582766
TI  - Network dynamics in the tumor microenvironment.
AB  - The evolutionary path from tumor initiation to metastasis can only be fully
      understood by considering cancer cells as part of a multi-species ecosystem
      within the tumor microenvironment. This paper reviews and suggests two important
      recent trends. Firstly, I review arguments that interactions among diverse cells
      in the tumor microenvironment create a distinct cellular environment that can
      confer growth advantages, resist interventions, and allow tumors to remain
      dormant for long periods. Second, I review and highlight a trend toward data
      rich, molecularly detailed, computational models of the tumor microenvironment. I
      argue that data-driven molecularly detailed tumor microenvironment models can now
      be built using data from multiple emerging high-throughput technologies, and that
      such models can pinpoint mechanisms of dysregulation and suggest specific drug
      targets and follow up experiments. 

PMID- 24582767
TI  - Multiple coronary fistulae: characterization by multimodality imaging.

PMID- 24582768
TI  - Running the figure to the ground: figure-ground segmentation during visual
      search.
AB  - We examined how figure-ground segmentation occurs across multiple regions of a
      visual array during a visual search task. Stimuli consisted of arrays of black
      and-white figure-ground images in which roughly half of each image depicted a
      meaningful object, whereas the other half constituted a less meaningful shape.
      The colours of the meaningful regions of the targets and distractors were either
      the same (congruent) or different (incongruent). We found that incongruent
      targets took longer to locate than congruent targets (Experiments 1, 2, and 3)
      and that this segmentation-congruency effect decreased when the number of search
      items was reduced (Experiment 2). Furthermore, an analysis of eye movements
      revealed that participants spent more time scrutinising the target before
      confirming its identity on incongruent trials than on congruent trials
      (Experiment 3). These findings suggest that the distractor context influences
      target segmentation and detection during visual search. 

PMID- 24582769
TI  - Atorvastatin inhibits CXCR7 induction to reduce macrophage migration.
AB  - We have recently reported that CXCR7, the alternate high affinity SDF-1 receptor,
      is induced during monocyte-to-macrophage differentiation, leading to increased
      macrophage phagocytosis linked to atherosclerosis. Statins, the most widely used
      medications for atherosclerosis, were shown to have pleiotropic beneficial
      effects independent of their cholesterol-lowering activity. This study aimed to
      determine whether induction of CXCR7 during macrophage differentiation is
      inhibited by statins and its significance on macrophage physiology. Here we show
      for the first time that atorvastatin dose-dependently inhibited CXCR7 mRNA and
      protein expression in THP-1 macrophages, without affecting the other SDF-1
      receptor, CXCR4. Pharmacotherapy relevant dose of atorvastatin affected neither
      cell viability nor macrophage differentiation. Suppression of CXCR7 expression
      was completely reversed by supplementation with mevalonate. Inhibition of
      squalene synthase, the enzyme committed to cholesterol biosynthesis, also
      decreased CXCR7 induction, albeit not as efficacious as atorvastatin. However,
      the geranylgeranyl transferase inhibitor, GGTI-286, the farnesyl transferase
      inhibitor, FTI-276, and the Rho kinase inhibitor, Y-27632, all failed to mimic
      the effect of atorvastatin, suggesting that the protein prenylation pathways are
      not critical for atorvastatin inhibition of CXCR7 induction. Interestingly, the
      dramatic effect of atorvastatin was only partially mimicked by other statins
      including pravastatin, fluvastatin, mevastatin, and simvastatin. Furthermore,
      activation of CXCR7 by SDF-1, TC14012, or I-TAC all prompted macrophage
      migration, which was significantly suppressed by atorvastatin treatment, but not
      by the CXCR4 antagonist. We conclude that atorvastatin modulates macrophage
      migration by down-regulating CXCR7 expression, suggesting a new CXCR7-dependent
      mechanism of atorvastatin to benefit atherosclerosis treatment beyond its lipid
      lowering effect. 

PMID- 24582770
TI  - Pelargonidin attenuates PDGF-BB-induced aortic smooth muscle cell proliferation
      and migration by direct inhibition of focal adhesion kinase.
AB  - Pelargonidin is a natural red pigment found in fruits and vegetables, and has
      been reported to exhibit various effects potentially beneficial for human health.
      However, the possible preventive effects of pelargonidin toward atherosclerosis
      and mechanisms involved have not been investigated to date. Here, we compared the
      effects of pelargonidin and its glucoside-conjugated form, pelargonidin-3
      glucoside (P3G), on proliferation and migration induced by platelet-derived
      growth factor (PDGF)-BB in human aortic smooth muscle cells (HASMCs).
      Pelargonidin, but not P3G, exhibited strong inhibitory effects against PDGF-BB
      induced HASMC proliferation and migration, while suppressing PDGF-BB-induced ex
      vivo rat aortic ring sprouting. Immunoblot analysis revealed that pelargonidin
      inhibited PDGF-BB-induced phosphorylation of focal adhesion kinase (FAK) as well
      as F-actin reduction, whereas Src, mitogen-activated protein kinases (MAPKs) and
      Akt phosphorylation status were not altered. We also observed that the anti
      proliferative and migratory effects of both pelargonidin and P3G corresponded
      with the extent of FAK inhibition. Both in vitro and ex vivo pull-down assays
      revealed that pelargonidin binds directly with FAK in an adenosine triphosphate
      competitive manner, suggesting that FAK could be a molecular target of
      pelargonidin. Interestingly, pelargonidin did not exhibit inhibitory effects on
      the proliferation, migration or FAK phosphorylation of human umbilical vein
      endothelial cells (HUVECs). Taken together, our results suggest that pelargonidin
      exhibits potential preventive effects toward atherosclerosis through the
      attenuation of HASMC proliferation and migration, as well as aortic sprouting via
      the direct inhibition of FAK activity. 

PMID- 24582771
TI  - Port site metastasis after surgery for renal cell carcinoma: harbinger of future
      metastasis.
AB  - PURPOSE: Port site metastasis is a rare occurrence after minimally invasive
      treatment for renal cell carcinoma. However, its prognostic implications are
      unclear because reports in the literature are heterogeneous in detail and
      followup. We clarify the significance of port site metastasis in cancer specific
      survival and broaden our understanding of this phenomenon. MATERIALS AND METHODS:
      A MEDLINE(r) search for published studies of renal cell carcinoma port site
      metastasis was performed. Contributing factors to port site metastasis, stage,
      Fuhrman grade, pathology, port site metastasis treatment method, followup
      protocol and long-term outcomes were collected. The corresponding authors of each
      publication were contacted to fill in details and provide long-term outcomes. We
      added 1 case from our recent experience. RESULTS: A total of 16 cases from 12
      authors (including ourselves) were found. Of the 12 authors 8 were available for
      correspondence and 9 cases were updated. Eventual outcomes were available for 11
      of the 16 cases and survival curves showed poor prognosis with a 31.8% overall 1
      year survival rate. Of the 16 cases 12 were radical nephrectomy and 4 were
      partial nephrectomy, and 13 involved multiple metastases in addition to the port
      site metastasis. Nine of the cases had no identifiable technical reason for port
      site metastasis formation such as specimen morcellation, absence of entrapment or
      tumor rupture. These tumors were uniformly aggressive, Fuhrman grade 3 or higher.
      CONCLUSIONS: Port site metastasis after minimally invasive surgery for renal cell
      carcinoma is a rare occurrence with a poor prognosis. In most cases port site
      metastasis is not an isolated metastasis but instead is a harbinger of
      progressive disease. While technical factors can have a role in port site
      metastasis formation, it appears that biological factors like high tumor grade
      also contribute.

PMID- 24582773
TI  - Paradoxical severe agitation induced by add-on high-doses quetiapine in schizo
      affective disorder.
AB  - We report the case of a 35-year-old patient suffering from schizo-affective
      disorder since the age of 19 years, treated by a combination of first-generation
      antipsychotics, zuclopenthixol (100 mg/day) and lithium (1200 mg/day) (serum
      lithium=0.85 mEq/l). This patient had no associated personality disorder
      (particularly no antisocial disorder) and no substance abuse disorder. Within the
      48 h following the gradual introduction of quetiapine (up to 600 mg/day), the
      patient presented severe agitation without an environmental explanation,
      contrasting with the absence of a history of aggressiveness or personality
      disorder. The diagnoses of manic shift and akathisia were dismissed. The
      withdrawal and the gradual reintroduction of quetiapine 2 weeks later, which led
      to another severe agitation, enabled us to attribute the agitation specifically
      to quetiapine.

PMID- 24582772
TI  - The relationship between cortisol responses to laboratory stress and cortisol
      profiles in daily life.
AB  - Relationships between cortisol responses to laboratory stress and cortisol output
      over the day have not been studied extensively. We tested associations between
      cortisol responses to a set of laboratory challenges (colour/word interference
      and mirror tracing) and three aspects of cortisol output over the day, namely
      total area under the curve (AUCday), the cortisol awakening response (CAR) and
      the slope of cortisol decline over the day. Participants were 466 men and women
      aged 54-76 years. We found that cortisol responses to laboratory stress were
      positively associated with cortisol AUCday independently of sex, age,
      socioeconomic status, smoking, body mass index, and time of laboratory testing
      (B=0.212, 95% C.I. 0.143-0.282, p<0.001). No associations between laboratory
      responses and the CAR or cortisol slope were observed. The laboratory-field
      association was not moderated by demographic or psychosocial factors. The study
      provides evidence for the ecological validity of acute laboratory stress testing.

PMID- 24582774
TI  - The utility of IFS (INECO Frontal Screening) for the detection of executive
      dysfunction in adults with bipolar disorder and ADHD.
AB  - Bipolar disorder (BD) and attention deficit hyperactivity disorder (ADHD) in
      adults share clinical symptoms. Both disorders present with executive functioning
      impairment. The detection of executive dysfunction usually requires the
      administration of an extensive neuropsychological battery. The Institute of
      Cognitive Neurology (INECO) Frontal Screening (IFS) is an efficient tool, which
      has been demonstrated to be useful for the detection of executive deficits in
      other diseases involving the prefrontal cortex. This study assessed the
      usefulness of the IFS in detecting the executive dysfunction of BD and ADHD
      adults, by means of a receiver-operating characteristic curve analysis and a
      multigroup discriminant function analysis. Twenty-four BD, 25 ADHD patients and
      25 controls were assessed with a battery that included the IFS and other measures
      of executive functioning. Our results showed that both patient groups performed
      significantly lower than controls on the IFS total score. Using a 27.5 point cut
      off score, the IFS showed good sensitivity and acceptable specificity to detect
      executive impairments in BD and ADHD patients. The IFS discriminated between
      controls and each patient group more reliably than other executive functions
      measures. Our results suggest that this tool could be a useful instrument to
      assess executive functions in BD and ADHD patients. 

PMID- 24582775
TI  - Facial emotion perception differs in young persons at genetic and clinical high
      risk for psychosis.
AB  - A large body of literature has documented facial emotion perception impairments
      in schizophrenia. More recently, emotion perception has been investigated in
      persons at genetic and clinical high-risk for psychosis. This study compared
      emotion perception abilities in groups of young persons with schizophrenia,
      clinical high-risk, genetic risk and healthy controls. Groups, ages 13-25,
      included 24 persons at clinical high-risk, 52 first-degree relatives at genetic
      risk, 91 persons with schizophrenia and 90 low risk persons who completed
      computerized testing of emotion recognition and differentiation. Groups differed
      by overall emotion recognition abilities and recognition of happy, sad, anger and
      fear expressions. Pairwise comparisons revealed comparable impairments in
      recognition of happy, angry, and fearful expressions for persons at clinical high
      risk and schizophrenia, while genetic risk participants were less impaired,
      showing reduced recognition of fearful expressions. Groups also differed for
      differentiation of happy and sad expressions, but differences were mainly between
      schizophrenia and control groups. Emotion perception impairments are observable
      in young persons at-risk for psychosis. Preliminary results with clinical high
      risk participants, when considered along findings in genetic risk relatives,
      suggest social cognition abilities to reflect pathophysiological processes
      involved in risk of schizophrenia. 

PMID- 24582776
TI  - Insulin, IGF-1 and GLP-1 signaling in neurodegenerative disorders: targets for
      disease modification?
AB  - Insulin and Insulin Growth Factor-1 (IGF-1) play a major role in body homeostasis
      and glucose regulation. They also have paracrine/autocrine functions in the
      brain. The Insulin/IGF-1 signaling pathway contributes to the control of neuronal
      excitability, nerve cell metabolism and cell survival. Glucagon like peptide-1
      (GLP-1), known as an insulinotropic hormone has similar functions and growth like
      properties as insulin/IGF-1. Growing evidence suggests that dysfunction of these
      pathways contribute to the progressive loss of neurons in Alzheimer's disease
      (AD) and Parkinson's disease (PD), the two most frequent neurodegenerative
      disorders. These findings have led to numerous studies in preclinical models of
      neurodegenerative disorders targeting insulin/IGF-1 and GLP-1 signaling with
      currently available anti-diabetics. These studies have shown that administration
      of insulin, IGF-1 and GLP-1 agonists reverses signaling abnormalities and has
      positive effects on surrogate markers of neurodegeneration and behavioral
      outcomes. Several proof-of-concept studies are underway that attempt to translate
      the encouraging preclinical results to patients suffering from AD and PD. In the
      first part of this review, we discuss physiological functions of insulin/IGF-1
      and GLP-1 signaling pathways including downstream targets and receptors
      distribution within the brain. In the second part, we undertake a comprehensive
      overview of preclinical studies targeting insulin/IGF-1 or GLP-1 signaling for
      treating AD and PD. We then detail the design of clinical trials that have used
      anti-diabetics for treating AD and PD patients. We close with future
      considerations that treat relevant issues for successful translation of these
      encouraging preclinical results into treatments for patients with AD and PD. 

PMID- 24582777
TI  - Remyelination after spinal cord injury: is it a target for repair?
AB  - After spinal cord injury (SCI) there is prolonged and dispersed oligodendrocyte
      cell death that is responsible for widespread demyelination. To regenerate this
      lost myelin, many investigators have transplanted myelin-producing cells as a
      treatment for contusive SCI. There are several documented examples of cellular
      transplantation improving function after injury, with the degree of myelin
      regeneration correlating with functional recovery. On the basis of these
      findings, remyelination is hypothesized to be a beneficial strategy to promote
      recovery after injury. As cellular transplantation is now entering clinical
      trials for treatment of SCI, it is important to dissect carefully whether
      accelerating remyelination after SCI is a valid clinical target. In this review
      we will discuss the consequences of demyelination and the potential benefits of
      remyelination as it relates to injury. Prolonged demyelination is hypothesized to
      enhance axonal vulnerability to degeneration, and is thereby thought to
      contribute to the axonal degeneration that underlies the permanent functional
      losses associated with SCI. Currently, strategies to promote remyelination after
      SCI are largely limited to cellular transplantation. This review discusses those
      strategies as well as new, and largely untested, modes of therapy that aim to
      coax endogenous cells residing adjacent to the injury site to differentiate in
      order to replace lost myelin. 

PMID- 24582778
TI  - Exploring the potential of endophytes from medicinal plants as sources of
      antimycobacterial compounds.
AB  - Natural product drug discovery has regained interest due to low production costs,
      structural diversity, and multiple uses of active compounds to treat various
      diseases. Attention has been directed towards medicinal plants as these plants
      have been traditionally used for generations to treat symptoms of numerous
      diseases. It is established that plants harbour microorganisms, collectively
      known as endophytes. Exploring the as-yet untapped natural products from the
      endophytes increases the chances of finding novel compounds. The concept of
      natural products targeting microbial pathogens has been applied to isolate novel
      antimycobacterial compounds, and the rapid development of drug-resistant
      Mycobacterium tuberculosis has significantly increased the need for new
      treatments against this pathogen. It remains important to continuously screen for
      novel compounds from natural sources, particularly from rarely encountered
      microorganisms, such as the endophytes. This review focuses on bioprospecting for
      polyketides and small peptides exhibiting antituberculosis activity, although
      current treatments against tuberculosis are described. It is established that
      natural products from these structure classes are often biosynthesised by
      microorganisms. Therefore it is hypothesised that some bioactive polyketides and
      peptides originally isolated from plants are in fact produced by their
      endophytes. This is of interest for further endophyte natural product
      investigations. 

PMID- 24582779
TI  - Classification of Colletotrichum coccodes isolates into vegetative compatibility
      groups using infrared attenuated total reflectance spectroscopy and multivariate
      analysis.
AB  - In this study the potential of infrared (IR) spectroscopy for the classification
      of Colletotrichum coccodes (C. coccodes) isolates into vegetative compatibility
      groups (VCGs) was evaluated. Isolates which belong to the same VCG may have
      similar pathological and physiological traits that differ from those that are not
      assigned to the same VCG. Early classification of isolates into VCGs is of a
      great importance for a better understanding of the epidemiology of the disease
      and improves its control. The main goal of the present study was to classify 14
      isolates of C. coccodes into VCGs and differentiate between them, based on their
      IR absorption spectra as obtained by the FTIR-ATR sampling technique. Advanced
      statistical and mathematical methods, including Principal Component Analysis
      (PCA) and Linear Discriminant Analysis (LDA), were applied to the spectra after
      manipulation. The results show that it is possible to assign the isolates into
      VCGs with more than 90% success based on the wavenumber low region (1800-800 cm(
      1)) and using 15 PCs. However, on the isolate level, the best differentiation
      results were obtained using PCA (15 PCs) and LDA for the combined regions (2990
      2800 cm(-1), 1800-800 cm(-1)), with identification success rates of 87.2%.

PMID- 24582781
TI  - Letter to the editor: patient-specific instrumentation does not shorten surgical
      time: a prospective, randomized trial.

PMID- 24582780
TI  - Characterization and detection of Vero cells infected with Herpes Simplex Virus
      type 1 using Raman spectroscopy and advanced statistical methods.
AB  - Herpes viruses are involved in a variety of human disorders. Herpes Simplex Virus
      type 1 (HSV-1) is the most common among the herpes viruses and is primarily
      involved in human cutaneous disorders. Although the symptoms of infection by this
      virus are usually minimal, in some cases HSV-1 might cause serious infections in
      the eyes and the brain leading to blindness and even death. A drug, acyclovir, is
      available to counter this virus. The drug is most effective when used during the
      early stages of the infection, which makes early detection and identification of
      these viral infections highly important for successful treatment. In the present
      study we evaluated the potential of Raman spectroscopy as a sensitive, rapid, and
      reliable method for the detection and identification of HSV-1 viral infections in
      cell cultures. Using Raman spectroscopy followed by advanced statistical methods
      enabled us, with sensitivity approaching 100%, to differentiate between a control
      group of Vero cells and another group of Vero cells that had been infected with
      HSV-1. Cell sites that were "rich in membrane" gave the best results in the
      differentiation between the two categories. The major changes were observed in
      the 1195-1726 cm(-1) range of the Raman spectrum. The features in this range are
      attributed mainly to proteins, lipids, and nucleic acids.

PMID- 24582783
TI  - Primary prophylaxis of invasive fungal diseases in allogeneic stem cell
      transplantation: revised recommendations from a consensus process by Gruppo
      Italiano Trapianto Midollo Osseo (GITMO).
AB  - This document updates and expands the recommendations on primary prophylaxis of
      invasive fungal diseases (IFD) in allogeneic hematopoietic stem cell
      transplantation (allo-HSCT) recipients, published in 2009 by the Gruppo Italiano
      Trapianto Midollo Osseo (GITMO). A consensus process was undertaken to describe
      and evaluate current information and practice regarding risk stratification and
      primary antifungal prophylaxis during the pre-engraftment and postengraftment
      phases after allo-HSCT. The revised recommendations were based on the evaluation
      of recent literature including a large, prospective, multicenter epidemiological
      study of allo-HSCT recipients conducted among the GITMO transplantation centers
      during the period of 2008 to 2010. It is intended as a guide for the
      identification of types and phases of transplantation at low, standard, and high
      risk for IFD, according to the underlying disease, transplantation, and post
      transplantation factors. The risk stratification was the critical determinant of
      the primary antifungal approach for allo-HSCT recipients. 

PMID- 24582782
TI  - Alternative donor transplantation for older patients with acute myeloid leukemia
      in first complete remission: a center for international blood and marrow
      transplant research-eurocord analysis.
AB  - We studied patients with acute myeloid leukemia (AML) over age 50 and in first
      complete remission (CR1) after adult unrelated donor (URD) (n = 441, 8/8 HLA
      matched; n = 94, 7/8 HLA matched) or umbilical cord blood (UCB; n = 205)
      transplantations. UCB recipients achieved CR1 within 8 weeks less often, and
      received reduced-intensity conditioning and cyclosporine-based graft-versus-host
      disease (GVHD) prophylaxis more often. Neutrophil recovery was slower in UCB (69%
      by day 28) compared with 8/8 HLA-matched URD (97%) and 7/8 HLA-matched (91%) (P <
      .001) recipients. Three-year transplantation-related mortality (TRM) was higher
      and leukemia-free survival (LFS) lower with UCB (35% and 28%, respectively)
      versus 8/8 HLA-matched URD (27% and 39%, respectively). TRM was higher in 7/8 HLA
      matched URD (41%, P = .01), but LFS was similar at 34% (P = .39). Three-year
      chronic GVHD was the lowest in UCB (28%) versus 53% and 59% in 8/8 and 7/8 HLA
      matched URD recipients, respectively. Three-year survival was 43% in 8/8 HLA
      matched URD (95% confidence interval [CI], 38% to 48%), 30% in UCB (95% CI, 23%
      to 37%) (P = .002) and 37% in 7/8 URD (95% CI, 27 to 46). Allotransplantation for
      AML in CR1 with any of these grafts extends LFS for over one third of older
      patients. In the absence of an 8/8 HLA-matched URD or when transplantation is
      needed urgently, UCB can provide extended survival. Less frequent chronic GVHD
      with UCB transplantation may be of particular value for older patients.

PMID- 24582785
TI  - Intracranial atherosclerosis in Chinese young adult stroke patients.
AB  - BACKGROUND: Until now, intracranial atherosclerosis has been less well studied
      because of its rarity. We sought to investigate the prevalence and risk factors
      of intracranial atherosclerosis in Chinese young adult stroke patients. METHODS:
      We retrospectively reviewed the medical records of consecutive young adult
      patients with first-ever ischemic stroke at our institution from May 2007 to May
      2012. The demographic features and risk factors of intracranial large-artery
      atherosclerotic (LAA) stroke were analyzed by comparison with other stroke
      subtypes. RESULTS: One hundred ninety-seven patients (age 39+/-9 years, 127 male)
      were recruited. There were 81 (41%) patients with LAA stroke, including 68 (35%)
      strokes because of intracranial stenosis. Male gender (P=.001), dyslipidemia
      (P=.015), smoking (P<.001), hypertension (P<.001), hyperhomocysteinemia (P=.003),
      and family history of stroke (P=.024) were more common in patients with
      intracranial LAA stroke than with non-LAA stroke. A high percentage of patients
      with intracranial LAA stroke had multiple modifiable risk factors (ie, at least 2
      of dyslipidemia, hypertension, diabetes mellitus, smoking, and
      hyperhomocysteinemia), much more than the patients with non-LAA stroke (82%
      versus 42%, P<.001). Simultaneous multiple modifiable risk factor exposure was
      the strongest "risk factor" for intracranial LAA stroke, with the adjusted odds
      ratio of 4.99. CONCLUSIONS: Intracranial atherosclerosis is highly prevalent in
      Chinese young stroke patients. Our results suggest that simultaneous exposure to
      multiple risk factors may contribute to the early development of intracranial
      atherosclerosis.

PMID- 24582786
TI  - The incidence of dysphagia in patients receiving cerebral reperfusion therapy
      poststroke.
AB  - BACKGROUND: The high prevalence of dysphagia after stroke leads to increased
      mortality, and cerebral reperfusion therapy has been effective in reducing
      neurologic deficits. The aim of this study was to investigate the severity and
      evolution of dysphagia and the occurrence of pneumonia in patients submitted to
      cerebral reperfusion therapy. METHODS: Seventy ischemic stroke patients were
      evaluated. Of these, 35 patients (group 1) were submitted to cerebral reperfusion
      therapy and 35 (group 2) did not receive thrombolytic treatment. The following
      were evaluated: severity of dysphagia by means of videofluoroscopy, evolution of
      oral intake rate by means of the Functional Oral Intake Scale, and the occurrence
      of pneumonia by international protocol. The relation between the severity of
      dysphagia and the occurrence of pneumonia with the treatment was evaluated
      through the chi-square test; the daily oral intake rate and its relation to the
      treatment were assessed by the Mann-Whitney test and considered significant if P
      is less than .05. RESULTS: The moderate and severe degrees of dysphagia were more
      frequent (P=.013) among the patients who were not submitted to cerebral
      reperfusion therapy. The daily oral intake evolved independently of the treatment
      type, without statistical significance when compared between the groups, whereas
      pneumonia occurred more frequently in group 2 (28%) in relation to group 1 (11%)
      and was associated with the worst degrees of dysphagia (P=.045). CONCLUSIONS: We
      can conclude that there is improvement in the oral intake rate in both groups,
      with lower severity of dysphagia and occurrence of pneumonia in ischemic stroke
      patients submitted to cerebral reperfusion therapy.

PMID- 24582784
TI  - Alpha 1-antitrypsin therapy mitigated ischemic stroke damage in rats.
AB  - Our objective is to develop a new therapy for the treatment of stroke. Currently,
      the only effective therapy for acute ischemic stroke is the thrombolytic agent
      recombinant tissue plasminogen activator. alpha1-Antitrypsin (AAT), a serine
      proteinase inhibitor with potent anti-inflammatory, anti-apoptotic,
      antimicrobial, and cytoprotective activities, could be beneficial in stroke. The
      goal of this study is to test whether AAT can improve ischemic stroke outcome in
      an established rat model. Middle cerebral artery occlusion was induced in male
      rats via intracranial (i.c.) microinjection of endothelin-1. Five to 10 minutes
      after stroke induction, rats received either i.c. or intravenous delivery of
      human AAT. Cylinder and vibrissae tests were used to evaluate sensorimotor
      function before and 72 hours after middle cerebral artery occlusion. Infarct
      volumes were examined via either 2,3,5-triphenyltetrazolium chloride assay or
      magnetic resonance imaging 72 hours after middle cerebral artery occlusion.
      Despite equivalent initial strokes, at 72 hours, the infarct volumes of the human
      AAT treatment groups (local and systemic injection) were statistically
      significantly reduced by 83% and 63% (P < .0001 and P < .05, respectively)
      compared with control rats. Human AAT significantly limited sensory motor system
      deficits. Human AAT could be a potential novel therapeutic drug for the
      protection against neurodegeneration after ischemic stroke, but more studies are
      needed to investigate the protective mechanisms and efficacy in other animal
      models. 

PMID- 24582787
TI  - Mild stroke and advanced age are the major reasons for exclusion from
      thrombolysis in stroke patients admitted within 4.5 hours.
AB  - BACKGROUND: Only 2%-3% of patients with acute ischemic stroke receive
      thrombolysis. The aim of this study was to identify the reasons for exclusion
      from thrombolysis in patients admitted within the therapeutic time window.
      METHODS: Patient data in the hospital stroke registry between January 2012 and
      September 2013 were retrospectively examined. All cases with a diagnosis of
      ischemic stroke were screened, and those admitted to the neurology wards within
      4.5 hours of symptom onset were analyzed. The reasons for exclusion from
      thrombolysis were examined. Logistic regression analysis was used to find
      independent predictors of thrombolysis treatment. RESULTS: Of the 1579 cases of
      ischemic stroke, 234 patients were admitted to the neurology ward within 4.5
      hours of symptom onset. A total of 57 patients received thrombolysis. The
      thrombolysis rate was 3.6% of all ischemic stroke patients. Of the 177 patients
      who were excluded from thrombolysis, 36.2% (n=64) had stroke of insufficient
      severity to warrant thrombolysis, and 24.9% (n=44) were older than 80 years.
      Logistic regression analysis showed that the interval between symptom onset and
      admission (odds ratio 20.24, 95% confidence interval 3.75-109.24) and history of
      ischemic stroke (odds ratio .11, 95% confidence interval .04-.34) affected the
      likelihood of thrombolysis. CONCLUSIONS: Mild stroke and advanced age were the
      major reasons for exclusion from thrombolysis in patients admitted within 4.5
      hours of symptom onset. Patients who were admitted early and those without a
      history of ischemic stroke were more likely to receive thrombolysis.

PMID- 24582788
TI  - An unusual cause of cerebellar hemorrhage in a young patient: essential
      thrombocythemia.
AB  - Essential thrombocythemia (ET) is a risk factor for ischemic stroke and, far more
      rarely, hemorrhage. We report the case of an untreated 32-year-old woman with a
      history of JAK2 V617F-positive ET with cerebellar and subarachnoid hemorrhages
      without evidence of sinus vein thrombosis. She was commenced on oral cytotoxic
      and antiplatelet therapy. This case report discusses the underlying mechanism of
      hemorrhagic thrombocythemia and the management dilemma presented by the
      recommended treatment implications. 

PMID- 24582789
TI  - Multiple ischemic strokes caused by nonbacterial thrombotic endocarditis because
      of gallbladder cancer: a case report.
AB  - We report a case of a 62-year-old woman with multiple ischemic strokes caused by
      nonbacterial thrombotic endocarditis (NBTE) because of gallbladder cancer.
      Transesophageal echocardiography showed NBTE on the mitral valve. The NBTE
      disappeared with anticoagulation treatment for 2 weeks. Abdominal computed
      tomography showed a gallbladder tumor that was surgically resected.
      Histopathologic studies showed poorly differentiated tumor cells and the
      production of mucin. Trousseau syndrome with gallbladder cancer is very rare. We
      suggest that the development of NBTE is related to the production of mucin. 

PMID- 24582790
TI  - Relationship between carotid artery remodeling and plaque vulnerability with T1
      weighted magnetic resonance imaging.
AB  - BACKGROUND: The aim of this study was to validate the relationship between
      carotid artery remodeling defined as the carotid remodeling index (CRI) and
      plaque vulnerability by comparing the degree of outward remodeling calculated
      using 3-dimensional inversion recovery-based T1-weighted imaging (magnetization
      prepared rapid acquisition gradient echo [MPRAGE]) with the symptomatology and
      histology of plaques extracted during carotid endarterectomy. METHODS: Sixty-one
      patients with 50% stenosis or more (North American Symptomatic Carotid
      Endarterectomy Trial criteria) were included. The average rate of stenosis was
      79.8%. The CRI was determined by measuring the external cross-sectional vessel
      area (CSVA) at the maximum stenosis of the internal carotid artery (ICA) and
      dividing it by the external CSVA at the distal ICA (unaffected by
      atherosclerosis) using MPRAGE imaging. RESULTS: The CRI was significantly higher
      in symptomatic patients compared with asymptomatic patients (1.98+/-.26 versus
      1.68+/-.24, P<.0001). A higher CRI positively correlated with the necrotic core
      area (r=.57, P<.0001) and negatively correlated with the fibrous cap thickness
      (r=-.33, P=.01). It was also significantly associated with severe intraplaque
      hemorrhage (P<.0001) and the prevalence of cap inflammation with macrophage
      (P=.03) and lymphocyte (P=.01) infiltration. CONCLUSIONS: The larger outward
      remodeling of the carotid artery on MPRAGE imaging had symptomatic carotid
      plaques and histologically vulnerable plaques. This study indicates that MPRAGE
      imaging is useful for the assessment of carotid artery remodeling.

PMID- 24582791
TI  - Endovascular treatment of sphenoid wing dural arteriovenous fistula with pure
      cortical venous drainage.
AB  - Curative endovascular treatment of sphenoid wing dural arteriovenous fistula
      (dAVF) with pure cortical venous drainage is challenging because of its rarity,
      lack of accessible dural sinus for transvenous embolization (TVE), and proximity
      of skull base vital regions. Direct surgery to disconnect venous reflux has been
      favored. We report the curative endovascular treatment of two sphenoid wing dAVFs
      with pure cortical venous drainage. One patient revealed complete obliteration of
      dAVF by a single session of transarterial embolization (TAE). As part of
      strategic TAE for this complex dAVF, we used a novel approach to create a
      complete flow-arrest condition in which coils and an occlusion balloon were
      combined. A liquid agent was then injected across the pathological fistula and
      into the parent venous apparatus, thereby occluding the lesion. The other patient
      was treated with percutaneous TVE after TAE was unsuccessful. With a specific
      strategy and appropriate devices, the microcatheter was successfully introduced
      through sigmoid sinus, transverse sinus, superior sagittal sinus, and refluxing
      cortical vein by puncture of the jugular vein. Coils were deployed at the venous
      side of the fistula, resulting in successful obliteration of the dAVF. Sphenoid
      wing dAVF with pure cortical venous drainage could be curable by endovascular
      treatment with proper strategy and instruments when anatomical condition permits.

PMID- 24582792
TI  - Symptomatic steno-occlusion of cerebral arteries and subsequent ischemic events
      in patients with acute ischemic stroke.
AB  - BACKGROUND: We aimed to assess the impact of symptomatic steno-occlusion (SYSO)
      of cerebral arteries and its characteristics on subsequent ischemic event (SIE)
      in patients with acute ischemic stroke. METHODS: Using a prospective stroke
      registry database, we identified consecutive patients with ischemic stroke who
      were hospitalized within 48 hours of symptom onset. SYSO denoted significant
      stenosis or occlusion of major cerebral arteries with ischemic lesions at the
      corresponding arterial territories and was characterized by its location and
      severity. Primary outcome was SIE that was defined as ischemic progression or
      recurrence within 1 year. RESULTS: In total, 1546 patients (age, 67.4 +/- 13.0
      years; median National Institutes of Health Stroke Scale score, 4) were enrolled
      in this study. The cumulative risk of SIE was 14.5% at 7 days, 14.9% at 14 days,
      15.5% at 90 days, and 16.9% at 1 year. Patients with SYSO had significantly
      higher SIE rates compared with those without SYSO (23.0% versus 11.6%). Of the
      characteristics of SYSO, the location, not the severity, was significantly
      associated with SIE (P < .001 and P = .186, respectively). Multiple (adjusted
      hazard ratio, 5.85; 95% confidence interval, 1.81-18.85), intracranial internal
      carotid artery (ICA) (3.54; 1.21-8.21), and extracranial ICA SYSO (2.88; 1.01
      8.21) raised the risk of SIE. CONCLUSIONS: Subsequent cerebral ischemic events
      (progression or recurrence) after an acute ischemic stroke occur mostly within
      several days of stroke onset and is associated with the location, but not the
      severity, of symptomatic steno-occlusion of cerebral arteries.

PMID- 24582794
TI  - The rise of operon-like gene clusters in plants.
AB  - Gene clusters are common features of prokaryotic genomes also present in
      eukaryotes. Most clustered genes known are involved in the biosynthesis of
      secondary metabolites. Although horizontal gene transfer is a primary source of
      prokaryotic gene cluster (operon) formation and has been reported to occur in
      eukaryotes, the predominant source of cluster formation in eukaryotes appears to
      arise de novo or through gene duplication followed by neo- and sub
      functionalization or translocation. Here we aim to provide an overview of the
      current knowledge and open questions related to plant gene cluster functioning,
      assembly, and regulation. We also present potential research approaches and point
      out the benefits of a better understanding of gene clusters in plants for both
      fundamental and applied plant science. 

PMID- 24582793
TI  - Association of rs2075575 and rs9951307 polymorphisms of AQP-4 gene with
      leukoaraiosis.
AB  - BACKGROUND: Leukoaraiosis (LA) is associated with structural and functional
      vascular changes that correlate with motor and gait disturbances, depressive
      symptoms, urinary disturbances, and dementia. The blood-brain barrier (BBB) plays
      a key role in development of lacunar stroke, leukoaraiosis, and other feature of
      cerebral small-vessel disease, and there are numerous studies examining changes
      in the BBB with normal aging and in dementia and LA. Aquaporin-4 (AQP-4), the
      primary water channel protein in the central nervous system, is involved in BBB
      development, function, and integrity, and its dysfunction induces several
      neurologic diseases. The aim of our study was to evaluate whether genetic
      variations in AQP-4 gene are associated with the development of LA. METHODS: DNA
      was amplified and the single-nucleotide polymorphisms in AQP-4 gene were
      investigated by melting curve analysis using real-time polymerase chain reaction.
      RESULTS: The frequency of both T allele and CT/TT genotypes of rs2075575 was
      significantly higher in LA group than in control group (C versus T, P = .0145; CC
      versus CT/TT, P = .038). However, no significant difference was observed between
      LA group and control group in rs9951307. Interestingly, the rs9951307 AG + GG
      genotype may confer a synergistic effect in odds ratio (OR) values when combined
      with the rs2075575 CT + TT genotypes (OR = 1.65 -> 2.51). The C-A haplotype was
      significantly different between LA group and the control group (P = .005). By
      stratified analysis, rs2075575 and rs9951307 polymorphisms were statistically
      significant in the subjects with hypertension and hemoglobin A1c (P < .05),
      whereas the rs2075575 polymorphism was associated with high serum cholesterol (P
      < .05) and the rs9951307 polymorphism was associated with low serum homocysteine
      (P < .05). CONCLUSIONS: Our results indicate that AQP-4 genetic variations and
      haplotypes might contribute to the risk factors for LA.

PMID- 24582795
TI  - C/EBP-alpha, involvement of a novel transcription factor in leptin-induced VCAM-1
      production in mouse chondrocytes.
AB  - Leptin and vascular cell adhesion molecules-1 (VCAM-1) are two important
      mediators in obesity-related osteoarthritis, while the molecular mechanism
      linking leptin to VCAM-1 production is still obscure. Here we show that leptin
      upregulates VCAM-1 mRNA and protein levels in a time- and dose-dependent manner.
      Mechanistically, leptin induces VCAM-1 promoter activity by increasing the
      expression of C/EBP-alpha and facilitating its binding to a newly identified
      element in the VCAM-1 gene. Gain or loss of function studies reveal a regulatory
      role of C/EBP-alpha on VCAM-1 expression. Finally, elevated plasma leptin level
      correlates to increased C/EBP-alpha and VCAM-1 production in chondrocytes from
      obese mice. 

PMID- 24582796
TI  - Impairments in top down attentional processes in right parietal patients:
      paradoxical functional facilitation in visual search.
AB  - It is well known that the right posterior parietal cortex (PPC) is involved in
      attentional processes, including binding features. It remains unclear whether PPC
      is implicated in top-down and/or bottom-up components of attention. We aim to
      clarify this by comparing performance of seven PPC patients and healthy controls
      (HC) in a visual search task involving a conflict between top-down and bottom-up
      processes. This task requires essentially a bottom-up feature search. However,
      top-down attention triggers feature binding for object recognition, designed to
      be irrelevant but interfering to the task. This results in top-down interference,
      prolonging the search reaction time. This interference was indeed found in our
      HCs but not in our PPC patients. In contrast to HC, the PPC patients showed no
      evidence of prolonged reactions times, even though they were slower than the HCs
      in search tasks without the conflict. This finding is an example of paradoxical
      functional facilitation (PFF) by brain damage. The PFF effect enhanced our
      patients' performance by reducing the top down interference. Our finding supports
      the idea that right PPC plays a crucial role in top-down attentional processes.
      In our search tasks, right PPC induces top-down interference either by directing
      spatial attention to achieve viewpoint invariance in shape recognition or by
      feature binding. 

PMID- 24582797
TI  - Greater sensitivity to nonaccidental than metric shape properties in preschool
      children.
AB  - Nonaccidental properties (NAPs) are image properties that are invariant over
      orientation in depth and allow facile recognition of objects at varied
      orientations. NAPs are distinguished from metric properties (MPs) that generally
      vary continuously with changes in orientation in depth. While a number of studies
      have demonstrated greater sensitivity to NAPs in human adults, pigeons, and
      macaque IT cells, the few studies that investigated sensitivities in preschool
      children did not find significantly greater sensitivity to NAPs. However, these
      studies did not provide a principled measure of the physical image differences
      for the MP and NAP variations. We assessed sensitivity to NAP vs. MP differences
      in a nonmatch-to-sample task in which 14 preschool children were instructed to
      choose which of two shapes was different from a sample shape in a triangular
      display. Importantly, we scaled the shape differences so that MP and NAP
      differences were roughly equal (although the MP differences were slightly
      larger), using the Gabor-Jet model of V1 similarity (Lades & et al., 1993). Mean
      reaction times (RTs) for every child were shorter when the target shape differed
      from the sample in a NAP than an MP. The results suggest that preschoolers, like
      adults, are more sensitive to NAPs, which could explain their ability to rapidly
      learn new objects, even without observing them from every possible orientation. 

PMID- 24582798
TI  - Face identity aftereffects increase monotonically with adaptor extremity over,
      but not beyond, the range of natural faces.
AB  - Face identity aftereffects have been used to test theories of the neural coding
      underlying expert face recognition. Previous studies reported larger aftereffects
      for adaptors that are morphed further from the average face than for adaptors
      closer to the average, which appeared to support opponent coding along face
      identity dimensions. However, only two levels were tested and it is not clear
      where they were located relative to the range of naturally occurring faces. This
      range is of interest given the functional need of the visual system both to
      produce good discrimination of real everyday faces and to process novel kinds of
      faces that we may encounter. Here, Experiment 1 establishes the boundary of faces
      judged as being able to occur in everyday life. Experiment 2 then shows that
      aftereffects increase with adaptor extremity up to this natural-range boundary,
      drop significantly immediately outside the boundary, and then remain stable with
      no drop towards zero even for highly distorted adaptors far beyond the boundary.
      Computational modelling shows that this unexpected pattern cannot be explained
      either by a simple opponent or by a classic multichannel model. However, its
      qualitative features can be captured either by a combination of opponent and
      multichannel coding (raising the possibility that not all identity-related face
      dimensions are opponent coded), or by a 3-pool model containing two S-shaped
      response channels and a central bell-shaped channel around the average face
      (raising the possibility of unexpected similarities with coding of eye and head
      direction).

PMID- 24582800
TI  - Growth and differentiation factor-5 (GDF-5) in the human intervertebral annulus
      cells and its modulation by IL-1beta and TNF-alpha in vitro.
AB  - Growth and differentiation factor-5 (GDF-5) is a member of the TGF-beta
      superfamily which regulates cell division and differentiation. GDF-5 attracted
      high interest because of its role in skeletal development, especially in
      cartilaginous sites. Little is known, however, about the role of GFD-5 in disc
      cell biology. The present work demonstrated the immunohistologic presence of GDF
      5 in human outer and inner annulus tissue. Microarray analysis of annulus cells
      showed significant upregulation of GDF-5 expression in herniated vs. non
      herniated lumbar discs (2.14-fold change, p=0.021). In vitro three-dimensional
      culture studies challenged human annulus cells with IL-1beta and TNF-alpha, two
      proinflammatory cytokines known to be elevated in the human degenerating disc.
      Exposure resulted in significant downregulation of GDF-5 during both TNF-alpha
      exposure (5.83-fold change, p=0.044) and IL-1beta exposure (3.38-fold change,
      p=0.015). In vitro findings suggest that the degenerating disc milieu, with high
      proinflammatory cytokine levels, may limit expression of GDF-5, resulting in
      limited regenerative capacity of the intact disc. 

PMID- 24582799
TI  - Calcium lactate pre-rinse increased fluoride protection against enamel erosion in
      a randomized controlled in situ trial.
AB  - OBJECTIVES: This in situ trial study was designed to evaluate whether calcium
      (Ca) pre-rinse would increase the fluoride (F) rinse protection against enamel
      erosion. METHODS: Fifteen volunteers participated in this split-mouth, 3-phase,
      crossover design study wearing a palatal appliance containing four sterilized
      bovine enamel slabs, for 10 days. In the 1st phase, five participants followed
      protocol A: daily rinse with a Ca lactate (CaL, 150mmol/L, 1min), followed by F
      (NaF 12mmol/L, 1min). Other five participants followed protocol B: daily rinse
      only with F, while the remainders followed protocol C: no rinse (negative
      control). Appliances were removed from the mouth and one side of the palatal
      appliance was exposed to a daily erosive challenge (0.05M citric acid, 90s); the
      other side served as control (deionized water - no erosion). In the 2nd phase
      volunteers were crossed over to other protocol and in the 3rd phase volunteers
      received the remaining protocol not yet assigned. Specimens were evaluated for
      surface loss using an optical profilometer. RESULTS: Repeated-measures three-way
      ANOVA (p=0.009) and Tukey's test showed that CaL pre-rinse followed by NaF rinse
      significantly decreased surface loss of enamel when performed prior to an erosive
      challenge in comparison with the condition in which NaF only was used.
      CONCLUSIONS: Pre-rinse with CaL may increase the protection exerted by NaF
      against erosive wear.

PMID- 24582801
TI  - The influence of comorbidity on mortality in ovarian cancer patients.
AB  - BACKGROUND: Ovarian cancer is a severe disease with a peak incidence in the older
      age groups where concurrent morbidity is common and could potentially influence
      mortality rates. OBJECTIVES: The aim was to study the influence of common
      comorbidity diagnoses on mortality in ovarian cancer patients. METHODS: The study
      population was patients with ovarian cancer in Sweden 1993-2006 (n=11.139)
      identified in the national Cancer Register. Comorbidity data was obtained from
      the Patient Register and mortality from Cause of Death Register. Mortality was
      analyzed with Cox' proportional hazards models and subgroup analyses were
      performed by age and tumor histology. RESULTS: Almost all of the assessed
      comorbidities increased mortality in ovarian cancer patients. Thromboembolism was
      the most hazardous comorbidity (HR=1.95, <1 year after cancer diagnosis and
      HR=7.83, 1-5 years after cancer diagnosis) followed by hematologic complications
      (HR=1.84 and 7.11 respectively) and infectious disease (HR=1.48 and 5.28
      respectively). The occurrence of diabetes mellitus and hypertension had less
      impact on mortality. CONCLUSION: Thromboembolism, hematologic complications and
      infections had a pronounced effect on mortality rates in women with ovarian
      cancer. The impact of comorbidity was mainly apparent among those with a more
      prosperous prognosis, such as longer time since cancer diagnosis, less aggressive
      tumors and younger age.

PMID- 24582802
TI  - Low dose PTH improves metaphyseal bone healing more when muscles are paralyzed.
AB  - Stimulation of bone formation by PTH is related to mechanosensitivity. The
      response to PTH treatment in intact bone could therefore be blunted by unloading.
      We studied the effects of mechanical loading on the response to PTH treatment in
      bone healing. Most fractures occur in the metaphyses, therefor we used a model
      for metaphyseal bone injury. One hind leg of 20 male SD rats was unloaded via
      intramuscular botulinum toxin injections. Two weeks later, the proximal unloaded
      tibia had lost 78% of its trabecular contents. At this time-point, the rats
      received bilateral proximal tibiae screw implants. Ten of the 20 rats were given
      daily injections of 5 MUg/kg PTH (1-34). After two weeks of healing, screw
      fixation was measured by pull-out, and microCT of the distal femur cancellous
      compartment was performed. Pull-out force provided an estimate for cancellous
      bone formation after trauma. PTH more than doubled the pull-out force in the
      unloaded limbs (from 14 to 30 N), but increased it by less than half in the
      loaded ones (from 30 to 44 N). In relative terms, PTH had a stronger effect on
      pull-out force in unloaded bone than in loaded bone (p=0.03). The results suggest
      that PTH treatment for stimulation of bone healing does not require simultaneous
      mechanical stimulation.

PMID- 24582803
TI  - Effects of osteogenic medium on healing of the experimental critical bone defect
      in a rabbit model.
AB  - Today, finding an ideal biomaterial to treat the large bone defects, delayed
      unions and non-unions remains a challenge for orthopedic surgeons and
      researchers. Several studies have been carried out on the subject of bone
      regeneration, each having its own advantages. At the same time, a variety of
      disadvantages still remain. The present study has been designed in vivo to
      evaluate the effects of osteogenic medium on healing of experimental critical
      bone defect in a rabbit model. Twenty New Zealand albino rabbits, 12 months old,
      of both sexes, weighing 2.0+/-0.5 kg were used in this study. An approximately
      10mm segmental defect was created in the mid portion of each radius as a critical
      size bone defect. In the osteogenic medium group (n=5) 1 ml osteogenic medium, in
      the maintenance medium group (n=5) 1 ml maintenance medium, and in the normal
      saline group (n=5) 1 ml normal saline were injected in the defected area while
      the defects of the rabbits of the control group (n=5) were left empty.
      Radiological evaluation was done on the 1st day and then at the 2nd, 4th, 6th and
      8th weeks post injury. Biomechanical and histopathological evaluations were done
      8 weeks post injury. The radiological, histological and biomechanical findings of
      the present study indicated a superior bone healing capability in the osteogenic
      and maintenance medium groups, by the end of 8 weeks post-surgery, in comparison
      to the normal saline and control groups. In conclusion, this study demonstrated
      that the osteogenic medium and maintenance medium could promote bone regeneration
      in long bone defects better than the control group in rabbit model.

PMID- 24582804
TI  - Cortical measurements of the tibia from high resolution peripheral quantitative
      computed tomography images: a comparison with synchrotron radiation micro
      computed tomography.
AB  - High resolution-peripheral quantitative computed tomography (HR-pQCT)
      measurements are carried out in clinical research protocols to analyze cortical
      bone. Micro-computed tomography (micro-CT) is a standard tool for ex vivo
      examination of bone in 3D. The aim of this work was to evaluate cortical
      measurements derived from HR-pQCT images compared to those from synchrotron
      radiation (SR) micro-CT in a distal position (4.2 cm from the distal pilon).
      Twenty-nine tibia specimens were scanned with HR-pQCT using protocols provided by
      the manufacturer. The standard measured outcomes included volumetric bone density
      (gHA/cm(3)) of the cortical region (Dcomp), and the cortical thickness (Ct.Th,
      mm). New features, such as cortical porosity (Ct.Po) and mean pore diameter
      (Ct.Po.Dm), were measured by an auto-contouring process. All tibias were
      harvested from the posterior region and imaged with SR micro-CT (voxel size=7.5
      MUm). The cortical thickness, (Ct.Thmicro-CT), porosity (PoV/TV), pore diameter,
      pore spacing, pore number, and degree of mineralization of bone (DMB) were
      obtained for SR micro-CT images. For standard measurements on HR-pQCT images,
      site matched analyses with micro-CT were completed to obtain Dcomplocal and
      Ct.Thlocal. Dcomp was highly correlated to PoV/TV (r=-0.84, p<10(-4)) but not to
      DMB. Dcomplocal was correlated to PoV/TV (r=-0.72, p<10(-4)) and to DMB (r=0.40,
      p>0.05). Ct.Thlocal and Ct.Thmicro-CT were moderately correlated (r=0.53,
      p<0.01). Ct.Th and Ct.Po results from the autocontouring process are influenced
      by the level of trabecularization of the cortical bone and need manual correction
      of the endosteal contour. Distal tibia is a reliable region to study cortical
      bone with Dcomp as the best parameter because it reflects both the micro-porosity
      (Havers canals) and macro-porosity (resorption lacunae) of the cortical bone.

PMID- 24582806
TI  - EFCAB7 and IQCE regulate hedgehog signaling by tethering the EVC-EVC2 complex to
      the base of primary cilia.
AB  - The Hedgehog (Hh) pathway depends on primary cilia in vertebrates, but the
      signaling machinery within cilia remains incompletely defined. We report the
      identification of a complex between two ciliary proteins, EFCAB7 and IQCE, which
      positively regulates the Hh pathway. The EFCAB7-IQCE module anchors the EVC-EVC2
      complex in a signaling microdomain at the base of cilia. EVC and EVC2 genes are
      mutated in Ellis van Creveld and Weyers syndromes, characterized by impaired Hh
      signaling in skeletal, cardiac, and orofacial tissues. EFCAB7 binds to a C
      terminal disordered region in EVC2 that is deleted in Weyers patients. EFCAB7
      depletion mimics the Weyers cellular phenotype-the mislocalization of EVC-EVC2
      within cilia and impaired activation of the transcription factor GLI2.
      Evolutionary analysis suggests that emergence of these complexes might have been
      important for adaptation of an ancient organelle, the cilium, for an animal
      specific signaling network. VIDEO ABSTRACT: 

PMID- 24582805
TI  - But do you think I'm cool? Developmental differences in striatal recruitment
      during direct and reflected social self-evaluations.
AB  - The current fMRI study investigates the neural foundations of evaluating oneself
      and others during early adolescence and young adulthood. Eighteen early
      adolescents (ages 11-14, M=12.6) and 19 young adults (ages 22-31, M=25.6)
      evaluated whether academic, physical, and social traits described themselves
      directly (direct self-evaluations), described their best friend directly (direct
      other-evaluations), described themselves from their best friend's perspective
      (reflected self-evaluations), or in general could change over time (control
      malleability-evaluations). Compared to control evaluations, both adolescents and
      adults recruited cortical midline structures during direct and reflected self
      evaluations, as well as during direct other-evaluations, converging with previous
      research. However, unique to this study was a significant three-way interaction
      between age group, evaluative perspective, and domain within bilateral ventral
      striatum. Region of interest analyses demonstrated a significant evaluative
      perspective by domain interaction within the adolescent sample only. Adolescents
      recruited greatest bilateral ventral striatum during reflected social self
      evaluations, which was positively correlated with age and pubertal development.
      These findings suggest that reflected social self-evaluations, made from the
      inferred perspective of a close peer, may be especially self-relevant, salient,
      or rewarding to adolescent self-processing--particularly during the progression
      through adolescence - and this feature persists into adulthood.

PMID- 24582808
TI  - [A guide to good practice for information security in the handling of personal
      health data by health personnel in ambulatory care facilities].
AB  - The appearance of electronic health records has led to the need to strengthen the
      security of personal health data in order to ensure privacy. Despite the large
      number of technical security measures and recommendations that exist to protect
      the security of health data, there is an increase in violations of the privacy of
      patients' personal data in healthcare organizations, which is in many cases
      caused by the mistakes or oversights of healthcare professionals. In this paper,
      we present a guide to good practice for information security in the handling of
      personal health data by health personnel, drawn from recommendations, regulations
      and national and international standards. The material presented in this paper
      can be used in the security audit of health professionals, or as a part of
      continuing education programs in ambulatory care facilities. 

PMID- 24582807
TI  - Germline quality control: eEF2K stands guard to eliminate defective oocytes.
AB  - The control of germline quality is critical to reproductive success and survival
      of a species; however, the mechanisms underlying this process remain unknown.
      Here, we demonstrate that elongation factor 2 kinase (eEF2K), an evolutionarily
      conserved regulator of protein synthesis, functions to maintain germline quality
      and eliminate defective oocytes. We show that disruption of eEF2K in mice reduces
      ovarian apoptosis and results in the accumulation of aberrant follicles and
      defective oocytes at advanced reproductive age. Furthermore, the loss of eEF2K in
      Caenorhabditis elegans results in a reduction of germ cell death and significant
      decline in oocyte quality and embryonic viability. Examination of the mechanisms
      by which eEF2K regulates apoptosis shows that eEF2K senses oxidative stress and
      quickly downregulates short-lived antiapoptotic proteins, XIAP and c-FLIPL by
      inhibiting global protein synthesis. These results suggest that eEF2K-mediated
      inhibition of protein synthesis renders cells susceptible to apoptosis and
      functions to eliminate suboptimal germ cells. 

PMID- 24582809
TI  - [The social representation that adolescents from Jalisco, Mexico have of early
      detection of breast cancer].
AB  - PURPOSE: To describe the social representation that adolescents from Jalisco,
      Mexico, have of early detection of breast cancer. DESIGN: Qualitative cross,
      analytical interpretative and based on the theory of social representations. Non
      probability sampling. LOCATION: Contact schools in basic education level of
      7municipalities of the State of Jalisco, Mexico, through various government and
      educational institutions. PARTICIPANTS: A hundred thirty five schooled
      adolescents, men and women. METHOD: Interview with 12 focus group 8
      12participants and 1 with 18participants. The interviews were transcribed in
      Atlas Ti program version 4.1 for a semiotic analysis to identify components of
      social representation. RESULTS: The precocious detection linked itself to the
      decrease of deaths for cancer of breast, long treatments and mastectomy, but
      little coverage was perceived to the mammary health of the teenager. They refer
      as limiter elements of the precocious detection the aspects of kind,
      psychological and of access to the information and services of health; since
      facilitators there was mentioned the transition of the limiter elements to
      facilitators. CONCLUSIONS: A favorable panorama appears on the level of awareness
      of the teenagers on his mammary health, identifying as a sector highly sensitive
      to the information about cancer of breast and with disposition to effect actions
      of early detection; there are identified as important challenge the generation of
      campaigns, educational materials and spaces of health focused on the teenager.

PMID- 24582810
TI  - Modulation of endothelin receptors in the failing right ventricle of the heart
      and vasculature of the lung in human pulmonary arterial hypertension.
AB  - AIMS: In pulmonary arterial hypertension (PAH), increases in endothelin-1 (ET-1)
      contribute to elevated pulmonary vascular resistance which ultimately causes
      death by right ventricular (RV) heart failure. ET antagonists are effective in
      treating PAH but lack efficacy in treating left ventricular (LV) heart failure,
      where ETA receptors are significantly increased. The aim was to quantify the
      density of ETA and ETB receptors in cardiopulmonary tissue from PAH patients and
      the monocrotaline (MCT) rat, which recapitulates some of the pathophysiological
      features, including increased RV pressure. MAIN METHODS: Radioligand binding
      assays were used to quantify affinity, density and ratio of ET receptors. KEY
      FINDINGS: In RV from human PAH hearts, there was a significant increase in the
      ratio of ETA to ETB receptors compared with normal hearts. In the RV of the MCT
      rat, the ratio also changed but was reversed. In both human and rat, there was no
      change in LV. In human PAH lungs, ETA receptors were significantly increased in
      the medial layer of small pulmonary arteries with no change detectable in MCT rat
      vessels. SIGNIFICANCE: Current treatments for PAH focus mainly on pulmonary
      vasodilatation. The increase in ETA receptors in arteries provides a mechanism
      for the beneficial vasodilator actions of ET antagonists. The increase in the
      ratio of ETA in RV also implicates changes to ET signalling although it is
      unclear if ET antagonism is beneficial but the results emphasise the unexploited
      potential for therapies that target the RV, to improve survival in patients with
      PAH.

PMID- 24582812
TI  - Comparison of pharmacological activity of macitentan and bosentan in preclinical
      models of systemic and pulmonary hypertension.
AB  - AIMS: The endothelin (ET) system is a tissular system, as the production of ET
      isoforms is mostly autocrine or paracrine. Macitentan is a novel dual ETA/ETB
      receptor antagonist with enhanced tissue distribution and sustained receptor
      binding properties designed to achieve a more efficacious ET receptor blockade.
      To determine if these features translate into improved efficacy in vivo, a study
      was designed in which rats with either systemic or pulmonary hypertension and
      equipped with telemetry were given macitentan on top of maximally effective doses
      of another dual ETA/ETB receptor antagonist, bosentan, which does not display
      sustained receptor occupancy and shows less tissue distribution. MAIN METHODS:
      After establishing dose-response curves of both compounds in conscious,
      hypertensive Dahl salt-sensitive and pulmonary hypertensive bleomycin-treated
      rats, macitentan was administered on top of the maximal effective dose of
      bosentan. KEY FINDINGS: In hypertensive rats, macitentan 30 mg/kg further
      decreased mean arterial blood pressure (MAP) by 19 mm Hg when given on top of
      bosentan 100 mg/kg (n=9, p<0.01 vs. vehicle). Conversely, bosentan given on top
      of macitentan failed to induce an additional MAP decrease. In pulmonary
      hypertensive rats, macitentan 30 mg/kg further decreased mean pulmonary artery
      pressure (MPAP) by 4 mm Hg on top of bosentan (n=8, p<0.01 vs. vehicle), whereas
      a maximal effective dose of bosentan given on top of macitentan did not cause any
      additional MPAP decrease. SIGNIFICANCE: The add-on effect of macitentan on top of
      bosentan in two pathological models confirms that this novel compound can achieve
      a superior blockade of ET receptors and provides evidence for greater maximal
      efficacy.

PMID- 24582811
TI  - Upstream and downstream mechanisms for the promoting effects of IGF-1 on
      differentiation of spermatogonia to primary spermatocytes.
AB  - AIM: The aim of this study is to delineate the mechanisms for the promoting the
      effects of insulin growth factor I (IGF1) on the differentiation of spermatogonia
      into primary spermatocytes. MAIN METHODS: We used organ culture of testicular
      fragments from mice to observe the effects of varying agents and siRNAs. Real
      time RT-PCR and immunoblotting analysis were employed to quantify expression of
      genes. Luciferase reporter gene assay was employed for verifying the targeting
      relationship between miRNA and protein-coding genes. KEY FINDINGS: During
      spermatogenesis while spermatozoa pass through epididymis and vas deferens for
      maturation, expression of IGF1 and its receptor IGF1R, p44/ERK1 and p42/ERK2, and
      PI3K was all upregulated, whereas let-7 miRNA family members let-7a/b/d/e/g/ were
      downregulated. We established both IGF1 and IGF1R as cognate target genes for let
      7; downregulation of let-7 resulted in upregulation of IGF1 and IGF1R during the
      early stage of differentiation from spermatogonia to primary spermatocytes.
      Transfection of let-7 inhibited, whereas transfection of anti-let-7 inhibitor
      enhanced the differentiation. The promoting effect of anti-let-7 was eliminated
      by PPP to block IGF1R phosphorylation. IGF1 activated ERK1/2 and PI3K and induced
      differentiation. PPP eliminated the activation of ERK1/2 and PI3K and inhibited
      the differentiation induced by IGF1. Specific inhibition of ERK1/2 by U0126 or
      PI3K by LY294002 reduced the IGF1-induced differentiation. Knockdown of ERK1/ERK2
      or PI3K by siRNAs also blocked IGF1-induced spermatogenesis. SIGNIFICANCE: Our
      study therefore identified downregulation of let-7 as an upstream mechanism for
      IGF1/IGF1R upregulation and activation of ERK1/2 and PI3K as a downstream
      mechanism mediating the IGF1 signaling cascade promoting differentiation of
      spermatogonia to primary spermatocytes.

PMID- 24582813
TI  - Effects of endothelin A receptor blockade in patients with ST-elevation acute
      coronary syndrome--a rhythmologic substudy.
AB  - AIMS: Ventricular arrhythmias are common after acute myocardial infarction (AMI).
      Endothelin (ET) is a mediator of microvascular dysfunction and cardiac remodeling
      with arrhythmogenic potential. The aim of this study was to assess safety and
      feasibility of selective ET-A receptor blockade in ST-elevation acute coronary
      syndrome (STE-ACS) within a larger randomized trial. MAIN METHODS: Patients with
      posterior-wall STE-ACS were randomly assigned to receive intravenous BQ-123 at
      400 nmol/min or placebo over 60 min, starting immediately prior to primary
      percutaneous coronary intervention. Twenty-four hour Holter recordings were
      performed during hospitalization for STE-ACS and after 6-8 weeks. The predefined
      primary endpoint was the documentation of ventricular tachycardia and/or late
      potentials at follow-up. KEY FINDINGS: There was no significant difference in the
      predefined primary endpoint at 45 (33-62) days (0/16 (0%) in BQ-123 treated
      patients vs. 1/14 (7%) in the placebo group, p=0.465). At 2 (1-3) days, an
      increase in the total number of supraventricular extrasystoles (SVES)/24 h in
      patients randomized to BQ-123 (45 (17-165) beats vs. 11 (5-72) beats in placebo
      treated patients, p=0.025) occurred. This increase was also observed at 45 days
      (105 (37-216) beats vs. 11 (3-98) beats in placebo treated patients, p=0.037).
      There was no significant difference regarding other rhythmologic secondary
      endpoints between the two groups. SIGNIFICANCE: Based on the analysis of long
      term ECG data, short-term administration of BQ-123 after AMI was safe. Because of
      the small sample size, no firm conclusion regarding antiarrhythmic efficacy can
      be drawn.

PMID- 24582814
TI  - Geranylgeranylacetone protects the heart via caveolae and caveolin-3.
AB  - AIMS: Geranylgeranylacetone (GGA) is commonly utilized to protect the gastric
      mucosa in peptic ulcer disease. Recently GGA has been shown to protect the
      myocardium from ischemia/reperfusion by activating heat shock proteins. However,
      the exact mechanism as to how GGA activates these protective proteins is unknown.
      Caveolae and caveolin-3 (Cav-3) have been implicated in ischemia, anesthetic, and
      opioid induced cardiac protection. Given the lipophilic nature of GGA it is our
      hypothesis that GGA induced cardiac protection requires caveolae and Cav-3. MAIN
      METHODS: We used an in vivo mouse model of ischemia-reperfusion injury and
      performed biochemical assays in excised hearts. KEY FINDINGS: GGA treated control
      mice revealed increased caveolae formation and caveolin-3 in buoyant fractions,
      mediating heat shock protein 70 activation. Furthermore, control mice treated
      with GGA were protected against ischemia/reperfusion injury whereas Cav-3
      knockout (Cav-3 KO) mice were not. Troponin levels confirmed myocardial damage.
      Finally, Cav-3 KO mice treated with GGA were not protected against mitochondrial
      swelling whereas control mice had significant protection. SIGNIFICANCE: This
      study showed that caveolae and caveolin-3 are essential in facilitating GGA
      induced cardiac protection by optimizing spatial and temporal signaling to the
      mitochondria.

PMID- 24582815
TI  - Comparison of rabbit antithymocyte globulin and Jurkat cell-reactive anti-T
      lymphocyte globulin as a first-line treatment for children with aplastic anemia.
AB  - The purpose of this study was to investigate the effects of rabbit antihuman
      thymocyte globulin (R-ATG) and Jurkat cell-reactive anti-T lymphocyte globulin
      (ATG-F) in the treatment of childhood aplastic anemia (AA) and compare their
      efficacy and side effects. A total of 53 children with AA were analyzed in the
      present study, including 32 cases of severe AA, 10 cases of very severe AA and 11
      cases of transfusion-dependent nonsevere AA. While receiving immunosuppressive
      therapy (IST), 29 and 24 patients, all of whom received long-term oral supplement
      with cyclosporin A (CSA), androgen, and traditional Chinese medicines, were
      treated with R-ATG and ATG-F, respectively. If necessary, the patients were also
      given supportive care such as component transfusion and/or infection control.
      Absolute counts of peripheral blood lymphocyte at various time points were
      dynamically measured after ATG therapy. According to the International AA
      Treatment and Effect standards, we found that there were no statistically
      significant differences in the response rate (70.83% vs. 68.97%, p > 0.05) and
      the overall survive rate (83.33% vs. 82.76%, p > 0.05) between the ATG-F and R
      ATG groups. In addition, no obvious differences were observed between these two
      groups in the response time, efficacy in severe AA and very severe AA, or the
      incidence rates of ATG-related adverse reactions. After ATG treatment, the extent
      of peripheral blood lymphocyte reduction and duration in peripheral blood were
      similar between the ATG-F and R-ATG groups. The results of this study showed that
      ATG-F and R-ATG had similar efficacy and adverse reactions in the first-line
      treatment of childhood AA, despite being derived from different immunogens. 

PMID- 24582816
TI  - Glutathione-mediated reversibility of covalent modification of ubiquitin carboxyl
      terminal hydrolase L1 by 1,2-naphthoquinone through Cys152, but not Lys4.
AB  - Covalent modification of cellular proteins by electrophiles affects electrophilic
      signal transduction and the dysfunction of enzymes that is involved in
      cytotoxicity. We have recently found a unique reaction which restores
      glyceraldehyde-3-phosphate dehydrogenase (GAPDH) that has been modified by 1,2
      naphthoquinone (1,2-NQ) through a glutathione (GSH)-dependent S-transarylation
      reaction. We report here that ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1)
      undergoes the same reaction. Exposure of human neuroblastoma SH-SY5Y cells to 1,2
      NQ after pretreatment with buthionine sulfoximine (BSO) to deplete GSH resulted
      in an enhancement of covalent modification of UCH-L1 by 1,2-NQ. With recombinant
      human UCH-L1, we demonstrated that UCH-L1 underwent arylation by 1,2-NQ through
      Cys152 and Lys4, thereby decreasing its catalytic activity. Addition of GSH to an
      incubation mixture of 1,2-NQ-UCH-L1 adduct partially restored this decline in
      enzyme activity which was accompanied by decreased covalent attachment of 1,2-NQ,
      together with production of 1,2-NQ-GSH adduct. UCH-L1 in which Lys4 was mutated
      exhibited a lower level of covalent modification and enzyme inhibition, but
      completely recovered after addition of GSH. Taken together, these results suggest
      that Cys152 modification in UCH-L1 by 1,2-NQ is reversible via GSH-mediated S
      transarylation reaction whereas Lys4 modification by 1,2-NQ is irreversible by
      GSH. Because UCH-L1 dysfunction has been associated with neurodegeneration, the
      electrophilic modification of Lys rather than Cys in UCH-L1 may be implicated in
      such neurodegenerative diseases. 

PMID- 24582817
TI  - 15-Deoxy-Delta(12,14)-prostaglandin J2 (15d-PGJ2) promotes apoptosis of HBx
      positive liver cells.
AB  - This study aims to investigate the inflammatory response characteristics of liver
      cells caused by HBV x protein (HBx) and the unique function of the PGE2 inhibitor
      on HBx-positive liver cells. Tetrazolium blue colorimetric method, flow
      cytometry, and Western blot were performed to detect the proliferation, cycle,
      and apoptosis protein expression of HBx-positive HL7702 liver and control cells.
      The effect of the PGE2 inhibitor 15-Deoxy-Delta(12,14)-prostaglandin J2 (15d
      PGJ2) on the growth of HL7702-HBx was also observed. HBx induces the PGE2
      accumulation in HL7702 liver cells and promotes their growth and inhibits their
      apoptosis. HL7702-HBx and HL7702 cells showed increased apoptosis rate, increased
      apoptosis-promoting protein expression, and reduced apoptosis-inhibiting protein
      expression under the effect of 15d-PGJ2, and the changes in HL7702-HBx cells were
      more significant than in HL7702 cells. HBx expression causes liver cells to be
      more sensitive to the apoptosis-promoting function of 15d-PGJ2. Therefore, the
      use of 15d-PGJ2 may be a new method for the prevention or treatment of
      inflammatory changes to cancer caused by HBV infection in liver cells. 

PMID- 24582818
TI  - Fatty acid profiles among the Inuit of Nunavik: current status and temporal
      change.
AB  - The Inuit undergo substantial changes in their lifestyle, but few data exist on
      how these changes occur in biomarkers, such as polyunsaturated fatty acids
      (PUFAs). Here, we report data from a cross-sectional survey conducted in 2004
      among 861 representative Nunavik Inuit adults, in whom FAs were measured in red
      blood cells (RBCs). FAs were also measured in plasma phospholipids (n=452) to
      assess temporal trend by comparing plasma PUFAs measured in 1992. Food intakes
      were estimated using a validated food frequency questionnaire. In 2004, marine
      food intake was 84+/-4g/d (+/-SEM). Adjusted-mean of RBC omega-3 was
      significantly higher, and omega-6 lower, in older age groups (Ptrend<0.001). In
      2004, plasma omega-3 was 25% lower, while omega-6 was 9% higher, compared to
      1992. Our study revealed that Nunavik Inuit adults still have high RBC omega-3,
      but show signs of nutritional transition - as indicated by lower omega-3 and
      higher trans-fats in RBCs of young compared to older. 

PMID- 24582819
TI  - To redistribute muscle activity in pain, or not: that is the question.

PMID- 24582820
TI  - Work and multisite musculoskeletal pain.

PMID- 24582823
TI  - Recombinant expression and purification of an ATP-dependent DNA ligase from
      Aliivibrio salmonicida.
AB  - The genome of the psychrophilic fish-pathogen Aliivibrio salmonicida encodes a
      putative ATP-dependent DNA ligase in addition to a housekeeping NAD-dependent
      enzyme. In order to study the structure and activity of the ATP dependent ligase
      in vitro we have undertaken its recombinant production and purification from an
      Escherichia coli based expression system. Expression and purification of this
      protein presented two significant challenges. First, the gene product was
      moderately toxic to E. coli cells, second it was necessary to remove the large
      amounts of E. coli DNA present in bacterial lysates without contamination of the
      protein preparation by nucleases which might interfere with future assaying. The
      toxicity problem was overcome by fusion of the putative ligase to large
      solubility tags such as maltose-binding protein (MBP) or Glutathione-S
      transferase (GST), and DNA was removed by treatment with a nuclease which could
      be inhibited by reducing agents. As the A. salmonicida ATP-dependent DNA ligase
      gene encodes a predicted leader peptide, both the full-length and mature forms of
      the protein were produced. Both possessed ATP-dependent DNA ligase activity, but
      the truncated form was significantly more active. Here we detail the first
      reported production, purification and preliminary characterization of active A.
      salmonicida ATP-dependent DNA ligase. 

PMID- 24582822
TI  - Highly efficient production of peptides: N-glycosidase F for N-glycomics
      analysis.
AB  - Peptide: N-glycosidase F (PNGase F) is an asparagine amidase produced by
      Flavobacterium meningosepticum that serves as a useful tool in the research on
      protein N-glycosylation. However, native PNGase F purified from F.
      meningosepticum and recombinant PNGase F expressed in Escherichia coli are
      obtained only at low levels, with the culture yield being no more than 15mg/L.
      Here, we report the efficient production of large amounts of recombinant PNGase
      F. First, a codon-optimized sequence encoding F. meningosepticum PNGase F was
      cloned into the pPICZaA vector, which was used to transform Pichia pastoris
      GS115. Clones were screened directly by dot blotting with an anti-6His-tag
      antibody, and then protein expression was induced in glass tubes to conduct
      validation assays. The clone expressing the highest level of PNGase F was
      selected for fermentation at a 5-L scale, and then the recombinant enzyme
      produced was purified in a single step using affinity chromatography, which
      yielded 800mg of the protein per liter of culture. The partly glycosylated
      recombinant PNGase F exhibited an identical specific activity as commercially
      available PNGase F when using RNase B or other N-glycoproteins as substrates.
      Thus, the method developed in this study can facilitate the large-scale
      production and use of PNGase F in the rapidly developing research field of N
      glycomics. 

PMID- 24582824
TI  - The syntax of action.

PMID- 24582825
TI  - Interoceptive inference: homeostasis and decision-making.

PMID- 24582821
TI  - Differential associations between impulsivity and risk-taking and brain
      activations underlying working memory in adolescents.
AB  - Increased impulsivity and risk-taking are common during adolescence and relate
      importantly to addictive behaviors. However, the extent to which impulsivity and
      risk-taking relate to brain activations that mediate cognitive processing is not
      well understood. Here we examined the relationships between impulsivity and risk
      taking and the neural correlates of working memory. Neural activity was measured
      in 18 adolescents (13-18 years) while they engaged in a working memory task that
      included verbal and visuospatial components that each involved encoding,
      rehearsal and recognition stages. Risk-taking and impulsivity were assessed using
      the Balloon Analogue Risk Task (BART) and the adolescent version of the Barratt
      Impulsiveness Scale-11 (BIS-11A), respectively. We found overlapping as well as
      distinct regions subserving the different stages of verbal and visuospatial
      working memory. In terms of risk-taking, we found a positive correlation between
      BART scores and activity in subcortical regions (e.g., thalamus, dorsal striatum)
      recruited during verbal rehearsal, and an inverse correlation between BART scores
      and cortical regions (e.g., parietal and temporal regions) recruited during
      visuospatial rehearsal. The BIS-11A evidenced that motor impulsivity was
      associated with activity in regions recruited during all stages of working
      memory, while attention and non-planning impulsivity was only associated with
      activity in regions recruited during recognition. In considering working memory,
      impulsivity and risk-taking together, both impulsivity and risk-taking were
      associated with activity in regions recruited during rehearsal; however, during
      verbal rehearsal, differential correlations were found. Specifically, positive
      correlations were found between: (1) risk-taking and activity in subcortical
      regions, including the thalamus and dorsal striatum; and, (2) motor impulsivity
      and activity in the left inferior frontal gyrus, insula, and dorsolateral
      prefrontal cortex. Therefore these findings suggest that while there may be some
      overlap in the neural correlates of working memory and their relationship to
      impulsivity and risk-taking, there are also important differences in these
      constructs and their relationship to the stages of working memory during
      adolescence.

PMID- 24582826
TI  - The potential efficacy of noninvasive ventilation with administration of a
      neutrophil elastase inhibitor for acute respiratory distress syndrome.
AB  - PURPOSE: Noninvasive ventilation (NIV) can reduce the need for invasive
      mechanical ventilation. The aim of this investigation was to determine whether
      the combination of NIV with administration of a neutrophil elastase inhibitor
      could improve outcome and respiratory conditions in acute respiratory distress
      syndrome (ARDS)-patients, according to the Berlin definition. METHODS: ARDS
      patients were treated with NIV and a neutrophil elastase inhibitor. Patients were
      classified as having mild, moderate, and severe ARDS. ARDS-patients were divided
      into survivors and nonsurvivors on day 28 after the induction of NIV. RESULTS: A
      total of 47 ARDS-patients received NIV, and 37 of these patients did not require
      endotracheal intubation. Eight mild, 17 moderate, and 10 severe ARDS-patients
      were alive on day 28 after the induction of NIV. When ARDS-patients were divided
      into groups based upon an initial PaO2/FiO2 greater or less than 150 torr, the
      serial changes of both the PaO2/FiO2 and the lung injury score improved
      dramatically in those patients with a PaO2/FiO2>150. The survival ratio showed
      statistically significant differences in mild and moderate ARDS-patients treated
      with the neutrophil elastase inhibitor. CONCLUSIONS: Administration of neutrophil
      elastase inhibitor with NIV may be associated with successful outcome in mild-to
      moderate ARDS-patients with initial PaO2/FiO2>150.

PMID- 24582827
TI  - Brain gadolinium enhancement along the ventricular and leptomeningeal regions in
      patients with aquaporin-4 antibodies in cerebral spinal fluid.
AB  - BACKGROUND: Aquaporin-4 (AQP4) is densely expressed in the ependymal region and
      leptomeninges, and it is susceptible to pathological responses triggered by
      antibodies from blood and cerebral spinal fluid (CSF). Therefore, enhancement of
      these regions may be related to neuromyelitis optica spectrum disorder (NMOSD).
      METHODS: MRI from a consecutive cohort of 84 subjects (NMOSD=47, multiple
      sclerosis [MS]=37) with AQP4 antibodies in serum and CSF were analyzed
      retrospectively. RESULTS: The brain was normal in five of the 47 patients with
      NMOSD and none of the MS patients showed a normal brain. Twelve patients in each
      group had parenchymal enhancing lesions. Of these, white matter enhancement was
      more frequently found in MS patients than in NMOSD patients (12/12 vs 4/12,
      p=0.001). "Cloud-like" enhancement was found in three NMOSD patients (3/12) and
      in one MS patient. Nine of the 12 NMOSD patients showed "pencil-thin" ependymal
      enhancement, whereas one of the 12 MS patients showed ependymal enhancement
      (p=0.003). Enhancement along the lateral ventricle was more frequently found in
      NMOSD patients than in MS patients (p=0.027), whereas enhancing lesions around
      the fourth ventricle tended to be more frequent in NMOSD patients than MS
      patients (p=0.097). Leptomeningeal enhancement around the brainstem was found in
      six (12.8%) NMOSD patients and in no MS patients (p=0.032). CONCLUSION:
      Enhancement of the leptomeninges and ventricular ependymal region more frequently
      occurs in NMOSD patients than in MS patients. This may be considered as
      characteristic clue in the diagnosis of NMOSD.

PMID- 24582829
TI  - Molecular mechanisms of regulated necrosis.
AB  - It is now clear that apoptosis does not constitute the sole genetically encoded
      form of cell death. Rather, cells can spontaneously undertake or exogenously be
      driven into a cell death subroutine that manifests with necrotic features, yet
      can be inhibited by pharmacological and genetic interventions. As regulated
      necrosis (RN) plays a major role in both physiological scenarios (e.g., embryonic
      development) and pathological settings (e.g., ischemic disorders), consistent
      efforts have been made throughout the last decade toward the characterization of
      the molecular mechanisms that underlie this cell death modality. Contrarily to
      initial beliefs, RN does not invariably result from the activation of a receptor
      interacting protein kinase 3 (RIPK3)-dependent signaling pathway, but may be
      ignited by distinct molecular networks. Nowadays, various types of RN have been
      characterized, including (but not limited to) necroptosis, mitochondrial
      permeability transition (MPT)-dependent RN and parthanatos. Of note, the
      inhibition of only one of these modules generally exerts limited cytoprotective
      effects in vivo, underscoring the degree of interconnectivity that characterizes
      RN. Here, we review the signaling pathways, pathophysiological relevance and
      therapeutic implications of the major molecular cascades that underlie RN. 

PMID- 24582831
TI  - Structure and assembly of filamentous bacteriophages.
AB  - Filamentous bacteriophages are interesting paradigms in structural molecular
      biology, in part because of the unusual mechanism of filamentous phage assembly.
      During assembly, several thousand copies of an intracellular DNA-binding protein
      bind to each copy of the replicating phage DNA, and are then displaced by
      membrane-spanning phage coat proteins as the nascent phage is extruded through
      the bacterial plasma membrane. This complicated process takes place without
      killing the host bacterium. The bacteriophage is a semi-flexible worm-like
      nucleoprotein filament. The virion comprises a tube of several thousand identical
      major coat protein subunits around a core of single-stranded circular DNA. Each
      protein subunit is a polymer of about 50 amino-acid residues, largely arranged in
      an alpha-helix. The subunits assemble into a helical sheath, with each subunit
      oriented at a small angle to the virion axis and interdigitated with neighbouring
      subunits. A few copies of "minor" phage proteins necessary for infection and/or
      extrusion of the virion are located at each end of the completed virion. Here we
      review both the structure of the virion and aspects of its function, such as the
      way the virion enters the host, multiplies, and exits to prey on further hosts.
      In particular we focus on our understanding of the way the components of the
      virion come together during assembly at the membrane. We try to follow a basic
      rule of empirical science, that one should chose the simplest theoretical
      explanation for experiments, but be prepared to modify or even abandon this
      explanation as new experiments add more detail. 

PMID- 24582832
TI  - Cytomodulin-1, a synthetic peptide abrogates oncogenic signaling pathways to
      impede invasion and angiogenesis in the hamster cheek pouch carcinogenesis model.
AB  - Constitutive activation of the various oncogenic signaling pathways plays a
      pivotal role in promoting malignant transformation. The aim of this study was to
      investigate the therapeutic potential of a synthetic bioactive heptapeptide
      cytomodulin-1 (CM-1) against hamster cheek pouch carcinomas based on its
      influence on the predominant carcinogenic signaling pathways - NF-kappaB,
      TGFbeta, and Wnt/beta-catenin and their downstream target events invasion and
      angiogenesis. Topical application of CM-1 to DMBA-painted hamsters significantly
      inhibited activation of the canonical NF-kappaB pathway by blocking kinase
      activity of IKKbeta and increasing the cytosolic accumulation of the inhibitor
      IkappaB-alpha. In addition, CM-1 inactivated IKKbeta by disrupting IKKbeta/Nemo
      interactions. CM-1 also hampered the activation of TGFbeta and Wnt/beta-catenin
      signaling by averting the phosphorylation of the key upstream ser/thr kinases
      TGFbeta RI and GSK-3beta respectively. Attenuation of these oncogenic signaling
      pathways by CM-1 also mitigated invasion and angiogenesis by suppressing the
      expression of pro-invasive matrix metalloproteinases, pro-angiogenic VEGF and HIF
      1alpha and upregulating the anti-angiogenic TIMP-2. Synthetic peptides such as CM
      1 that target multiple key molecules in oncogenic signaling pathways and their
      downstream events are ideal candidate agents for cancer chemotherapy.

PMID- 24582830
TI  - Functions of crystallins in and out of lens: roles in elongated and post-mitotic
      cells.
AB  - The vertebrate lens evolved to collect light and focus it onto the retina. In
      development, the lens grows through massive elongation of epithelial cells
      possibly recapitulating the evolutionary origins of the lens. The refractive
      index of the lens is largely dependent on high concentrations of soluble proteins
      called crystallins. All vertebrate lenses share a common set of crystallins from
      two superfamilies (although other lineage specific crystallins exist). The alpha
      crystallins are small heat shock proteins while the beta- and gamma-crystallins
      belong to a superfamily that contains structural proteins of uncertain function.
      The crystallins are expressed at very high levels in lens but are also found at
      lower levels in other cells, particularly in retina and brain. All these proteins
      have plausible connections to maintenance of cytoplasmic order and chaperoning of
      the complex molecular machines involved in the architecture and function of
      cells, particularly elongated and post-mitotic cells. They may represent a suite
      of proteins that help maintain homeostasis in such cells that are at risk from
      stress or from the accumulated insults of aging. 

PMID- 24582834
TI  - Executive summary of the Consensus Statement on monitoring HIV: pregnancy, birth,
      and prevention of mother-to-child transmission.
AB  - The main objective in the management of HIV-infected pregnant women is prevention
      of mother-to-child transmission; therefore, it is essential to provide universal
      antiretroviral treatment, regardless of CD4 count. All pregnant women must
      receive adequate information and undergo HIV serology testing at the first visit.
      If the serological status is unknown at the time of delivery, or in the immediate
      postpartum, HIV serology testing has to be performed as soon as possible. In this
      document, recommendations are made regarding the health of the mother and from
      the perspective of minimizing mother-to-child transmission.

PMID- 24582833
TI  - Binding studies of a large antiviral polyamide to a natural HPV sequence.
AB  - PA1 is a large hairpin polyamide (dImPyPy-beta-PyPyPy-gamma-PyPy-beta-PyPyPyPy
      beta-Ta; Py = pyrrole, Im = imidazole, beta = beta alanine) that targets the
      sequence 5'-WWGWWWWWWW-3' (W = A or T) and is effective in eliminating HPV16 in
      cell culture (Edwards, T. G., Koeller, K. J., Slomczynska, U., Fok, K., Helmus,
      M., Bashkin, J. K., Fisher, C., Antiviral Res. 91 (2011) 177-186). Described here
      are its DNA binding properties toward a natural DNA, a 523 bp portion of HPV16
      (2150-2672) containing three predicted perfect match sites. Strategies for
      obtaining binding data on large fragments using capillary electrophoresis are
      also described. Using an Fe EDTA conjugate of PA1, 19 affinity cleavage (AC)
      patterns were detected for this fragment. In many cases, there are multiple
      possible binding sequences (perfect, single and double mismatch sites) consistent
      with the AC data. Quantitative DNase I footprinting analysis indicates that
      perfect and most single mismatch sites bind PA1 with Kds between 0.7 and 4 nM,
      indicating excellent tolerance for the latter. Double mismatch sites exhibit Kds
      between 12 and 62 nM. A large fraction of the accessible sequence is susceptible
      to PA1 binding, much larger than predicted based on the literature of polyamide
      DNA recognition rules.

PMID- 24582835
TI  - [Study of the role of miRNA in mesenchymal stem cells isolated from
      osteoarthritis patients].
AB  - OBJECTIVE: MiRNAs act as gene silencers that are involved in the regulation of
      essential cell functions. miR-335 is involved in regulating cell differentiation
      processes in progenitor cells. Mesenchymal stem cells (MSCs) are progenitor cells
      of chondrocytes and osteoblasts responsible for homeostatic maintenance of
      cartilage and bone. The aim of this study was to determine a possible
      relationship between the expression of miR-335 and osteoarthritis. METHODS: MSCs
      obtained from the bone marrow of 3 osteoarthritic patients and 3 controls with no
      clinical signs of osteoarthritis or osteoporosis were cultured and phenotypically
      and functionally characterised in a 3-step culture. Expression levels of miR-335
      and the mesoderm-specific transcript gene -MEST- that controls its expression
      were determined by quantitative PCR. RESULTS: Differences in the expression
      levels of miR-335 and MEST (median [interquartile range]: 1.69 [0.85-1.74], and
      3.85 [3.20-5.67] were detected between MSCs isolated from patients with
      osteoarthritis and controls. Although the differences detected did not reach
      statistical significance (P=.1), a clear trend towards lower expression of miR
      335 in osteoarthritis MSCs was observed. CONCLUSIONS: Given that miR-335 has the
      different genes involved in the Wnt signalling pathway as potential targets, the
      observed trend may help to ascertain, at least partially, some of the alterations
      which determine the onset or progression of osteoarthritis, and can therefore
      serve for the design of future therapeutic targets for the treatment of this
      disease.

PMID- 24582836
TI  - Viral-human chimeric transcript predisposes risk to liver cancer development and
      progression.
AB  - The mutagenic effect of hepatitis B (HBV) integration in predisposing risk to
      hepatocellular carcinoma (HCC) remains elusive. In this study, we performed
      transcriptome sequencing of HBV-positive HCC cell lines and showed transcription
      of viral-human gene fusions from the site of genome integrations. We discovered
      tumor-promoting properties of a chimeric HBx-LINE1 that, intriguingly, functions
      as a hybrid RNA. HBx-LINE1 can be detected in 23.3% of HBV-associated HCC tumors
      and correlates with poorer patient survival. HBx-LINE1 transgenic mice showed
      heightened susceptibility to diethylnitrosamine-induced tumor formation. We
      further show that HBx-LINE1 expression affects beta-catenin transactivity, which
      underlines a role in activating Wnt signaling. Thus, this study identifies a
      viral-human chimeric fusion transcript that functions like a long noncoding RNA
      to promote HCC. 

PMID- 24582838
TI  - Comparative cost-effectiveness of the HeartWare versus HeartMate II left
      ventricular assist devices used in the United Kingdom National Health Service
      bridge-to-transplant program for patients with heart failure.
AB  - BACKGROUND: Patients with advanced heart failure may receive a left ventricular
      assist device (LVAD) as part of a bridge-to-transplant (BTT) strategy. The United
      Kingdom National Health Service (UK NHS) has financed a BTT program in which the
      predominant LVADs used have been the HeartMate II (HM II; Thoratec, Pleasanton,
      CA) and HeartWare (HW; HeartWare International, Inc. Framingham, MA). We aimed to
      compare the cost-effectiveness of the use of these within the NHS program.
      METHODS: Individual patient data from the UK NHS Blood and Transplant Data Base
      were analyzed with Kaplan-Meier and competing outcomes methodologies. Outcomes
      were time to death, time to heart transplant (HT), and cumulative incidences of
      HT, death on LVAD support, and LVAD explantation. A semi-Markov multistate
      economic model was built to assess cost-effectiveness. The perspective was from
      the NHS, discount rates were 3.5%. Outcomes were quality-adjusted life-years
      (QALYs) and incremental cost (2011 prices in GBL) per QALY (ICER) for HW vs HM
      II. RESULTS: Survival was better with HW support than with HM II. Cumulative
      incidence of HT was low for both groups (11% at ~2 years). HW patients accrued
      4.99 lifetime QALYs costing L258,913 ($410,970), HM II patients accrued 3.84
      QALYs costing L231,871 ($368,048); deterministic and probabilistic ICERs for HW
      vs HM II were L23,530 ($37,349) and L20,799 ($33,014), respectively. CONCLUSIONS:
      Patients In the UK BTT program who received the HW LVAD had a better clinical
      outcome than those who received the HM II, and the HW was more cost-effective.
      This result needs to be reassessed in a randomized controlled trial comparing the
      2 devices.

PMID- 24582837
TI  - Assessment of myocardial viability and left ventricular function in patients
      supported by a left ventricular assist device.
AB  - BACKGROUND: Chronically supported left ventricular assist device (LVAD) patients
      may be candidates for novel therapies aimed at promoting reverse remodeling and
      myocardial recovery. However, the effect of hemodynamic unloading with a LVAD on
      myocardial viability and LV function in chronically supported LVAD patients has
      not been fully characterized. We aimed to develop a non-invasive imaging protocol
      to serially quantify native cardiac structure, function, and myocardial viability
      while at reduced LVAD support. METHODS: Clinically stable (n = 18) ambulatory
      patients (83% men, median age, 61 years) supported by a HeartMate II (Thoratec,
      Pleasanton, CA) LVAD (median durations of heart failure 4.6 years and LVAD
      support 7 months) were evaluated by echocardiography and technetium-99m ((99m)Tc)
      sestamibi single photon emission computed tomography (SPECT) imaging at baseline
      and after an interval of 2 to 3 months. Echocardiographic measures of LV size and
      function, including speckle tracking-derived circumferential strain, were
      compared between ambulatory and reduced LVAD support at baseline and between
      baseline and follow-up at reduced LVAD support. The extent of myocardial
      viability by SPECT was compared between baseline and follow-up at reduced LVAD
      support. RESULTS: With reduction in LVAD speeds (6,600 rpm; interquartile range:
      6,200, 7,400 rpm), LV size increased, LV systolic function remained stable, and
      filling pressures nominally worsened. After a median 2.1 months, cardiac
      structure, function, and the extent of viable myocardium, globally and
      regionally, was unchanged on repeat imaging while at reduced LVAD speed.
      CONCLUSIONS: In clinically stable chronically supported LVAD patients, intrinsic
      cardiac structure, function, and myocardial viability did not significantly
      change over the pre-specified time frame. Echocardiographic circumferential
      strain and (99m)Tc-sestamibi SPECT myocardial viability imaging may provide
      useful non-invasive end points for the assessment of cardiac structure and
      function, particularly for phase II studies of novel therapies aimed at promoting
      reverse remodeling and myocardial recovery in LVAD patients.

PMID- 24582839
TI  - Chromosome loss caused by DNA fragmentation induced in main nuclei and
      micronuclei of human lymphoblastoid cells treated with colcemid.
AB  - Aneuploidy, a change in the number of chromosomes, plays an essential role in
      tumorigenesis. Our previous study demonstrated that a loss of a whole chromosome
      is induced in human lymphocytes by colcemid, a well-known aneugen. Here, to
      clarify the mechanism for colcemid-induced chromosome loss, we investigated the
      relationship between chromosome loss and DNA fragmentation in human
      lymphoblastoid cells treated with colcemid (an aneugen) compared with methyl
      methanesulfonate (MMS; a clastogen). We analyzed the number of fluorescence in
      situ hybridization (FISH) signals targeted for a whole chromosome 2 in
      cytokinesis-blocked binucleated TK6 cells and WTK-1 cells treated with colcemid
      and MMS, and concurrently detected DNA fragmentation by terminal deoxynucleotidyl
      transferase dUTP nick end labeling (TUNEL) assay. Results revealed that DNA
      fragmentation occurred in 60% of all binucleated TK6 cells harboring colcemid
      induced chromosome loss (30% of micronuclei and 30% of main nuclei). DNA
      fragmentation was observed in colcemid-induced micronuclei containing a whole
      chromosome but not in MMS-induced micronuclei containing chromosome fragments. In
      contrast, colcemid-induced nondisjunction had no effect on induction of DNA
      fragmentation, suggesting that DNA fragmentation was triggered by micronuclei
      containing a whole chromosome but not by micronuclei containing chromosome
      fragments or nondisjunction. In addition, the frequency of binucleated cells
      harboring chromosome loss with DNA fragmentation in micronuclei or main nuclei
      was higher in wild-type p53 TK6 cells than in mutated-p53 WTK-1 cells treated
      with colcemid. Taken together, these present and previous results suggest that
      colcemid-induced chromosome loss is caused by DNA fragmentation, which is
      triggered by a micronucleus with a whole chromosome and controlled by the p53
      dependent pathway. 

PMID- 24582841
TI  - Low levels of urinary liver-type fatty acid-binding protein may indicate a lack
      of kidney protection during aortic arch surgery requiring hypothermic circulatory
      arrest.
AB  - STUDY OBJECTIVE: To examine the change in liver-type fatty acid-binding protein
      (L-FABP) levels in patients undergoing aortic arch surgery and the correlation
      between L-FABP and postoperative acute kidney injury. DESIGN: Prospective
      observational study. SETTING: Operating room of a general hospital. PATIENTS: 36
      adult patients. INTERVENTIONS AND MEASUREMENTS: Urine samples were obtained to
      measure urinary L-FABP at initiation of cardiopulmonary bypass (CPB) and 5
      minutes after termination of hypothermic circulatory arrest. MAIN RESULTS: 22
      (61.1%) patients developed acute kidney injury within a 48-hour period. L-FABP
      increases more than a thousand-fold were found. In patients who subsequently
      developed acute kidney injury, significant increases in L-FABP were noted from
      2.9 (3.6) ng/mg of creatinine before CPB to 62.1 (995.6) ng/mg of creatinine 5
      minutes after termination of circulatory arrest. Values in patients who did not
      develop acute kidney injury increased from 1.1 (5.7) ng/mg before CPB to 1133.0
      (6358.8) ng/mg of creatinine showing a significant mean difference (P = 0.011).
      The area under the L-FABP receiver operating characteristic curve at 5 minutes
      after termination of circulatory arrest was 0.758. A cutoff value of 75.13 ng/mg
      of creatinine yielded both good sensitivity (1.000) and specificity (0.546) for
      detecting non-acute kidney injury. Patients who developed acute kidney injury
      after aortic arch surgery demonstrated lower levels of urinary L-FABP.
      CONCLUSIONS: Low levels of urinary L-FABP may indicate kidney injury and lack of
      renal protection.

PMID- 24582840
TI  - Stormwater drains and catch basins as sources for production of Aedes aegypti and
      Culex quinquefasciatus.
AB  - We present data showing that structures serving as drains and catch basins for
      stormwater are important sources for production of the mosquito arbovirus vectors
      Aedes aegypti and Culex quinquefasciatus in Merida City, Mexico. We examined 1761
      stormwater drains - located in 45 different neighborhoods spread across the city 
      over dry and wet seasons from March 2012 to March 2013. Of the examined
      stormwater drains, 262 (14.9%) held water at the time they were examined and 123
      yielded mosquito immatures. In total, we collected 64,560 immatures representing
      nine species. The most commonly encountered species were Cx. quinquefasciatus
      (n=39,269) and Ae. aegypti (n=23,313). Ae. aegypti and Cx. quinquefasciatus were
      collected during all 11 months when we found water-filled stormwater drains, and
      both were found in stormwater drains located throughout Merida City. We also
      present data for associations between structural characteristics of stormwater
      drains or water-related characteristics and the abundance of mosquito immatures.
      In conclusion, stormwater drains produce massive numbers of Ae. aegypti and Cx.
      quinquefasciatus across Merida City, both in the wet and dry seasons, and
      represent non-residential development sites that should be strongly considered
      for inclusion in the local mosquito surveillance and control program. 

PMID- 24582842
TI  - Wrist kinematic coupling and performance during functional tasks: effects of
      constrained motion.
AB  - PURPOSE: To quantify the coupled motion of the wrist during selected functional
      tasks and to determine the effects of constraining this coupled motion using a
      radial-ulnar deviation blocking splint on performance of these tasks. METHODS:
      Ten healthy, right-handed men performed 15 trials during selected functional
      tasks with and without a splint, blocking radial and ulnar deviation. The
      following tasks were performed: dart throwing, hammering, basketball free-throw,
      overhand baseball and football throwing, clubbing, and pouring. Kinematic
      coupling parameters (coupling, kinematic path length, flexion-extension range of
      motion, radial-ulnar deviation range of motion, flexion-extension offset, and
      radial-ulnar deviation offset) and performance were determined for each
      functional task. A generalized estimation equation model was used to determine
      whether each kinematic coupling parameter was significantly different across
      tasks. A repeated-measures generalized estimation equation model was used to test
      for differences in performance and kinematic coupling parameters between the free
      and splinted conditions. RESULTS: Wrist motion exhibited linear coupling between
      flexion-extension and radial-ulnar deviation, demonstrated by R(2) values from
      0.70 to 0.99. Average wrist coupling and kinematic path lengths were
      significantly different among tasks. Coupling means and kinematic path lengths
      were different between free and splinted conditions across all tasks other than
      pouring. Performance was different between wrist conditions for dart throwing,
      hammering, basketball shooting, and pouring. CONCLUSIONS: Wrist kinematic
      coupling parameters are task specific in healthy individuals. Functional
      performance is decreased when wrist coupling is constrained by an external
      splint. CLINICAL RELEVANCE: Surgical procedures that restrict wrist coupling may
      have a detrimental effect on functional performance as defined in the study.
      Patients may benefit from surgical reconstructive procedures and wrist
      rehabilitation protocols designed to restore kinematic coupling.

PMID- 24582843
TI  - Carpal tunnel release in patients with diabetes: a 5-year follow-up with matched
      controls.
AB  - PURPOSE: To compare clinical outcomes 5 years after carpal tunnel release among
      patients with and without diabetes. METHODS: In a prospective consecutive series,
      35 patients with diabetes (median age, 54 y; 15 type 1 and 20 type 2 diabetes)
      with carpal tunnel syndrome were age- and sex-matched with 31 control patients
      without diabetes (median age, 51 y) with idiopathic carpal tunnel syndrome.
      Exclusion criteria were other nerve entrapment, cervical radiculopathy,
      inflammatory joint disease, thyroid disorder, previous wrist fracture, and long
      term exposure to vibrating tools. Participants were examined independently at
      baseline, 1 year, and 5 years after surgery for sensory function (Semmes
      Weinstein), motor function (abductor pollicis brevis muscle strength and grip
      strength), cold intolerance, and completion of the Boston Carpal Tunnel
      Questionnaire symptom severity and functional status score. RESULTS: Five years
      after surgery, the overall attendance rate for clinical examinations and
      completion of the Boston Carpal Tunnel Questionnaire were 86% and 95%,
      respectively. Between 1 and 5 years after surgery, there was a tendency toward a
      decrease in sensory function but an increase in motor function, with no
      statistically significant difference between groups. Cold intolerance
      demonstrated long-term significant improvement for patients with diabetes. The
      improvement in symptom severity and functional status score, as well as the large
      effect size, were maintained at 5 years in both patient groups. CONCLUSIONS: Long
      term improvement in patients with diabetes remained after carpal tunnel release
      to the same extent as for patients without diabetes. Furthermore, improvement in
      cold intolerance in patients with diabetes suggests the potential for the long
      term regeneration of small nerve fibers. TYPE OF STUDY/LEVEL OF EVIDENCE:
      Prognostic I.

PMID- 24582844
TI  - Efficacy and safety of ultrasound-guided distal blocks for analgesia without
      motor blockade after ambulatory hand surgery.
AB  - PURPOSE: To assess the suitability of ultrasound-guided (USG), single-injection
      distal block(s) for pain management after outpatient hand and wrist bone surgery.
      METHODS: We conducted a retrospective review of 125 of 198 consecutive ambulatory
      surgery patients who underwent hand and wrist bone surgery between June 2010 and
      January 2012. All patients received a USG axillary block using a short-acting
      local anesthetic (lidocaine) and secondary 1, 2, or 3 (median, radial, or ulnar)
      USG distal analgesic block(s) using a long-acting local anesthetic (ropivacaine).
      All patients were contacted by phone on the first postoperative day. All patients
      received a concomitant prescription of acetaminophen and nonsteroidal anti
      inflammatory drugs with opioids as a rescue treatment. Effectiveness and duration
      of the distal nerve blocks, compliance with analgesic treatment and rescue
      opioids requirement, opioid-related side effects, prolonged upper limb motor
      block, quality of sleep on first postoperative night, and patient satisfaction
      were evaluated. RESULTS: Most distal analgesic blocks were effective (120 of 125;
      96%), with an average duration of nearly 12 hours On the first day after surgery,
      28 patients (23%) had a numeric verbal scale greater than 3, although 14 of them
      had taken the rescue opioids. No patient reported prolonged motor blockade or
      insensate limb. Opioid-related side effects occurred in 23% of patients.
      CONCLUSIONS: After hand and wrist bone surgery, USG selective distal blocks using
      a long-acting local anesthetic, combined with oral analgesics, were effective in
      a large majority of patients. However, pain control was suboptimal for some
      especially painful procedures such as wrist surgery, trapeziometacarpal
      arthrodesis, and finger amputation. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic
      IV.

PMID- 24582845
TI  - Nerve transfer from triceps medial head and anconeus to deltoid for axillary
      nerve palsy.
AB  - PURPOSE: To report our results with reconstruction of the axillary nerve by
      transferring the branch to the triceps lower medial head and anconeus to the
      anterior division of the axillary nerve. METHODS: This study included 9 patients
      with isolated injury of the axillary nerve. Their average age +/- SD was 35 +/- 9
      years, and the mean interval +/- SD between injury and surgery was 6.6 +/- 2.6
      months. Through a posterior arm approach, the radial nerve branch to the lower
      triceps medial head and anconeus was transferred to the anterior division of the
      axillary nerve. We observed patients for a mean of 34 +/- 7 months. At final
      evaluation, we measured range of shoulder motion, shoulder abduction and elbow
      extension strength, and abduction endurance. Patients were assessed via the
      deltoid extension lag test and abduction-in-internal-rotation test. RESULTS: All
      patients recovered deltoid function and maintained full active elbow extension.
      Seven of 9 patients recovered from lagging abduction in internal rotation.
      Abduction strength improved from approximately 40% that of the normal side at 90
      degrees  of abduction preoperatively to 60% of normal strength postoperatively.
      There was improved endurance in abduction from approximately 25% to 65% that of
      the normal side, which was sufficient to eliminate all reports of shoulder pain
      or fatigability. CONCLUSIONS: Transfer of the radial nerve branch for the lower
      triceps medial head and anconeus to the anterior division of the axillary nerve
      proved to be an effective method of deltoid reinnervation. TYPE OF STUDY/LEVEL OF
      EVIDENCE: Therapeutic IV.

PMID- 24582846
TI  - Cast immobilization with and without immobilization of the thumb for nondisplaced
      and minimally displaced scaphoid waist fractures: a multicenter, randomized,
      controlled trial.
AB  - PURPOSE: The aim of this prospective randomized trial was to test the null
      hypothesis that there was no difference in the percentage of the fracture line of
      scaphoid waist fractures that demonstrated bridging bone on computed tomography
      (CT) 10 weeks after injury between patients treated in a below-elbow cast
      including or excluding the thumb. METHODS: A total of 62 patients with a CT or
      magnetic resonance image-confirmed nondisplaced or minimally displaced fracture
      of the scaphoid were enrolled in a prospective, multicenter, randomized trial
      comparing treatment in a below-elbow cast including or excluding the thumb. There
      were 55 waist and 7 distal fractures (owing to a miscommunication at 3 of the
      centers). We adhered to intention-to-treat principles. The primary outcome was
      the extent of union on CT performed after 10 weeks of cast treatment, expressed
      as a percentage of the fracture line that had bridging bone, determined by
      musculoskeletal radiologists blinded to treatment. Secondary study outcomes
      included wrist motion; grip strength; the Mayo Modified Wrist Score; the
      Disabilities of the Arm, Shoulder and Hand score; a visual analog scale for pain;
      and radiographic union at 6 months after injury. RESULTS: There was a significant
      difference in the average extent of union on CT at 10 weeks (85% vs 70%) favoring
      treatment with a cast excluding the thumb. The overall union rate was 98%. The 1
      exception was a patient in the thumb immobilization group who elected operative
      treatment 1 week after enrollment, used crutches, and failed to heal. There were
      no significant differences between groups for wrist motion; grip strength; Mayo
      Modified Wrist Score; Disabilities of the Arm, Shoulder, and Hand score; or pain
      intensity. CONCLUSIONS: Immobilization of the thumb appears unnecessary for CT or
      magnetic resonance image-confirmed nondisplaced or minimally displaced fractures
      of the waist of the scaphoid. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic I.

PMID- 24582847
TI  - Superficial angiomyxoma of the thumb mimicking a malignant bone tumor: case
      report.
AB  - Superficial angiomyxoma is a distinctive cutaneous soft tissue neoplasm commonly
      involving dermal and subcutaneous tissues and showing a prominent angiomyxoid
      matrix interspersed with numerous blood vessels. We report a case of superficial
      angiomyxoma in a 70-year-old man who presented with a fungating swelling on the
      distal phalanx of the thumb mimicking a malignant tumor. The diagnosis of
      superficial angiomyxoma was made based on histopathology and
      immunohistochemistry. We report this lesion because of its rare presentation with
      extensive distal phalangeal osteolysis mimicking a malignant bone tumor. 

PMID- 24582848
TI  - Retinoids as potential targets for Alzheimer's disease.
AB  - Vitamin A and its derivatives, the retinoids, modulate several physiological and
      pathological processes through their interactions with nuclear retinoid receptor
      proteins termed as retinoic acid receptors (RARs) and retinoid X receptors
      (RXRs). An increasing body of evidence signifies the existence of retinoid
      signaling in diverse brain areas including cortex, amygdala, hypothalamus,
      hippocampus, and striatum suggesting its involvement in adult brain functions.
      Defective retinoid signaling has been evidenced in the pathology of Alzheimer's
      disease. Reports demonstrate that vitamin A deprived mice exhibit serious defects
      in spatial learning and memory signifying its importance in the maintenance of
      memory functions. Retinoid signaling impacts the development of AD pathology
      through multiple pathways. Ligand activation of RAR and RXR in APP/PS1 transgenic
      mice ameliorated the symptoms of AD and reduced amyloid accumulation and tau
      hyperphosphorylation. Retinoids also reduce the production of pro-inflammatory
      cytokines and chemokines by astrocytes and the microglia. Studies also suggest
      that neuronal cell lines treated with retinoid agonists exhibit an up-regulation
      in the expression and activity of choline acetyltransferase (ChAT). Reports
      depict that retinoic acid isomers enhance, the expression of genes linked with
      cholesterol efflux e.g. apoe, abca-1 and abcg-1 proteins in astrocytes.
      Furthermore numerous studies also indicate antioxidant potential of retinoids.
      Through this review we concisely summarize the biology of retinoids, emphasizing
      on their probable neuroprotective mechanisms that will help to elucidate the
      pivotal role of these receptors in AD pathology. 

PMID- 24582849
TI  - The antinociceptive effect of intravenous imipramine in colorectal distension
      induced visceral pain in rats: the role of serotonergic and noradrenergic
      receptors.
AB  - It has been shown that imipramine, a tricyclic antidepressant (TCA), is a potent
      analgesic agent. However, the effect of imipramine on visceral pain has not been
      extensively investigated. In the current study, our aim was to characterise the
      putative analgesic effect of intravenous imipramine on visceral pain in rats. Our
      second aim was to assess the involvement of serotonergic (5-HT2,3,4) and
      noradrenergic (alpha(2A, 2B, 2C)) receptor subtypes in this putative
      antinociceptive effect of imipramine. Male Sprague Dawley rats (250-300 g) were
      implanted with venous catheters for drug administration and implanted with
      enamelled nichrome electrodes for electromyography of the external oblique
      muscles. Noxious visceral stimulation was applied via by colorectal distension
      (CRD). The visceromotor responses (VMRs) to CRD were quantified
      electromyographically before and after imipramine administration at 5, 15, 30,
      60, 90 and 120 min. In the antagonist groups, the agents were administered 10 min
      before imipramine. The administration of imipramine (5-40 mg/kg) produced a dose
      dependent reduction in VMR. The administration of yohimbine (a nonselective
      alpha2-adrenoceptor antagonist, 1 mg/kg), BRL-44408 (an alpha(2A)-adrenoceptor
      antagonist, 1 mg/kg) or MK-912 (an alpha2C-adrenoceptor antagonist, 300 MUg/kg)
      but not imiloxan (an alpha(2B)-adrenoceptor antagonist, 1 mg/kg) inhibited the
      antinociceptive effect of imipramine (20 mg/kg). Additionally, ketanserin (a 5
      HT2 receptor antagonist, 0.5, 1, and 2 mg/kg) and GR113808 (a 5-HT4 receptor
      antagonist, 1 mg/kg) enhanced, and ondansetron (a 5-HT3 receptor antagonist, 0.5,
      1, and 2 mg/kg) failed to alter the imipramine-induced antinociceptive effect.
      Our data demonstrated that, in the CDR-induced rat visceral pain model,
      intravenous imipramine appeared to have antinociceptive potential and that
      alpha(2A)-/alpha(2C)-adrenoceptors and 5-HT2/5-HT4 receptors may be responsible
      for the antinociceptive effect of imipramine on visceral pain in rats.

PMID- 24582850
TI  - Ameliorating effect of spinosin, a C-glycoside flavonoid, on scopolamine-induced
      memory impairment in mice.
AB  - Spinosin is a C-glycoside flavonoid isolated from the seeds of Zizyphus jujuba
      var. spinosa. This study investigated the effect of spinosin on cholinergic
      blockade-induced memory impairment in mice. Behavioral tests were conducted using
      the passive avoidance, Y-maze, and Morris water maze tasks to evaluate the memory
      ameliorating effect of spinosin. Spinosin (10 or 20mg/kg, p.o.) significantly
      ameliorated scopolamine-induced cognitive impairment in these behavioral tasks
      with a prolonged latency time in the passive avoidance task, an increased
      percentage of spontaneous alternation in the Y-maze task and a lengthened
      swimming time in target quadrant in the Morris water maze task. In addition, a
      single administration of spinosin in normal naive mice also enhanced the latency
      time in the passive avoidance task. To identify the mechanism of the memory
      ameliorating effect of spinosin, receptor antagonism analysis and Western
      blotting were performed. The ameliorating effect of spinosin on scopolamine
      induced memory impairment was significantly antagonized by a sub-effective dose
      (0.5mg/kg, i.p.) of 8-hydroxy-2-(di-N-propylamino)tetralin, a 5-HT1A receptor
      agonist. In addition, spinosin significantly increased the expression levels of
      phosphorylated extracellular signal-regulated kinases and cAMP response element
      binding proteins in the hippocampus. Taken together, these results indicate that
      the memory-ameliorating effect of spinosin may be, in part, due to the
      serotonergic neurotransmitter system, and that spinosin may be useful for the
      treatment of cognitive dysfunction in diseases such as Alzheimer's disease.

PMID- 24582851
TI  - Chronic exposure to WIN55,212-2 affects more potently spatial learning and memory
      in adolescents than in adult rats via a negative action on dorsal hippocampal
      neurogenesis.
AB  - Several epidemiological studies show an increase in cannabis use among
      adolescents, especially in Morocco for being one of the major producers in the
      world. The neurobiological consequences of chronic cannabis use are still poorly
      understood. In addition, brain plasticity linked to ontogeny portrays adolescence
      as a period of vulnerability to the deleterious effects of drugs. The aim of this
      study was to investigate the behavioral neurogenic effects of chronic exposure to
      the cannabinoid agonist WIN55,212-2 during adolescence, by evaluating the
      emotional and cognitive performances, and the consequences on neurogenesis along
      the dorso-ventral axis of the hippocampus in adult rats. WIN55,212 was
      administered intraperitoneally (i.p.) once daily for 20 days to adolescent (27-30
      PND) and adult Wistar rats (54-57 PND) at the dose of 1mg/kg. Following a 20 day
      washout period, emotional and cognitive functions were assessed by the Morris
      water maze test and the two-way active avoidance test. Twelve hours after, brains
      were removed and hippocampal neurogenesis was assessed using the doublecortin
      (DCX) as a marker for cell proliferation. Our results showed that chronic
      WIN55,212-2 treatment significantly increased thigmotaxis early in the training
      process whatever the age of treatment, induced spatial learning and memory
      deficits in adolescent but not adult rats in the Morris water maze test, while it
      had no significant effect in the active avoidance test during multitrial training
      in the shuttle box. In addition, the cognitive deficits assessed in adolescent
      rats were positively correlated to a decrease in the number of newly generated
      neurons in dorsal hippocampus. These data suggest that long term exposure to
      cannabinoids may affect more potently spatial learning and memory in adolescent
      compared to adult rats via a negative action on hippocampal plasticity.

PMID- 24582852
TI  - Targeting receptor tyrosine kinases in osteosarcoma and Ewing sarcoma: current
      hurdles and future perspectives.
AB  - Osteosarcoma (OS) and Ewing sarcoma (ES) are the two most common types of primary
      bone cancer, which mainly affect children and young adults. Despite intensive
      multi-modal treatment, the survival of both OS and ES has not improved much
      during the last decades and new therapeutic options are awaited. One promising
      approach is the specific targeting of transmembrane receptor tyrosine kinases
      (RTKs) implicated in these types of bone cancer. However, despite encouraging in
      vitro and in vivo results, apart from intriguing results of Insulin-like Growth
      Factor-1 Receptor (IGF-1R) antibodies in ES, clinical studies are limited or
      disappointing. Primary resistance to RTK inhibitors is frequently observed in OS
      and ES patients, and even patients that initially respond well eventually develop
      acquired resistance. There are, however, a few remarks to make concerning the
      current set-up of clinical trials and about strategies to improve RTK-based
      treatments in OS and ES. This review provides an overview concerning current RTK
      mediated therapies in OS and ES and discusses the problems observed in the
      clinic. More importantly, we describe several strategies to overcome resistance
      to RTK inhibitors which may significantly improve outcome of OS and ES patients. 

PMID- 24582853
TI  - Learning to read new words in individuals with Down syndrome: testing the role of
      phonological knowledge.
AB  - This study examined the effect of word level phonological knowledge on learning
      to read new words in Down syndrome compared to typical development. Children were
      taught to read 12 nonwords, 6 of which were pre-trained on their phonology. The
      16 individuals with Down syndrome aged 8-17 years were compared first to a group
      of 30 typically developing children aged 5-7 years matched for word reading and
      then to a subgroup of these children matched for decoding. There was a marginally
      significant effect for individuals with Down syndrome to benefit more from
      phonological pre-training than typically developing children matched for word
      reading but when compared to the decoding-matched subgroup, the two groups
      benefitted equally. We explain these findings in terms of partial decoding
      attempts being resolved by word level phonological knowledge and conclude that
      being familiar with the spoken form of a new word may help children when they
      attempt to read it. This may be particularly important for children with Down
      syndrome and other groups of children with weak decoding skills. 

PMID- 24582854
TI  - Occupation and communication programs for post-coma persons with or without
      consciousness disorders who show extensive motor impairment and lack of speech.
AB  - These two studies were aimed at extending the assessment of technology-aided
      programs for post-coma persons with extensive motor impairment and lack of
      speech. Specifically, Study I assessed a new program arrangement, in which
      stimulation access and caregiver attention could be obtained with variations of
      the same response (i.e., single- versus double-hand closure) by three
      participants who were diagnosed at the upper level of the minimally conscious
      state at the start of the study. Study II was aimed at enabling two persons who
      had emerged from a minimally conscious state to engage in leisure activities,
      listen to audio-recordings of family members, and send and receive messages. The
      responses selected for these participants were hand pressure and eyelid closure,
      respectively. The results of both studies were positive. The participants of
      Study I increased their responding to increase their stimulation input and
      caregiver interaction. The participants of Study II managed to successfully
      select all the options the program included (i.e., the leisure options, as well
      as the family and communication options). General implications of the programs
      and the related technology packages for intervention with post-coma persons with
      multiple disabilities are discussed. 

PMID- 24582855
TI  - Web server for tilt-pair validation of single particle maps from electron
      cryomicroscopy.
AB  - Three-dimensional structures of biological assemblies may be calculated from
      images of single particles obtained by electron cryomicroscopy. A key step is the
      correct determination of the orientation of the particle in individual image
      projections. A useful tool for validation of the quality of a 3D map and its
      consistency with images is tilt-pair analysis. In a successful tilt-pair test,
      the relative angle between orientations assigned to each image of a tilt-pair
      agrees with the known relative rotation angle of the microscope specimen holder
      during the experiment. To make the procedure easy to apply to the increasing
      number of single particle maps, we have developed software and a web server for
      tilt-pair analysis. The tilt-pair analysis program reports the overall agreement
      of the assigned orientations with the known tilt angle and axis of the experiment
      and the distribution of tilt transformations for individual particles recorded in
      a single image field. We illustrate application of the validation tool to several
      single particle specimens and describe how to interpret the scores. 

PMID- 24582856
TI  - Hydrogen sulfide in plants: from dissipation of excess sulfur to signaling
      molecule.
AB  - Sulfur is essential in all organisms for the synthesis of amino acids cysteine
      and methionine and as an active component of numerous co-factors and prosthetic
      groups. However, only plants, algae, fungi, and some prokaryotes are capable of
      using the abundant inorganic source of sulfur, sulfate. Plants take sulfate up,
      reduce it, and assimilate into organic compounds with cysteine being the first
      product of the pathway and a donor of reduced sulfur for synthesis of other S
      containing compounds. Cysteine is formed in a reaction between sulfide, derived
      from reduction of sulfite and an activated amino acid acceptor, O-acetylserine.
      Sulfide is thus an important intermediate in sulfur metabolism, but numerous
      other functions in plants has been revealed. Hydrogen sulfide can serve as an
      alternative source of sulfur for plants, which may be significant in anaerobic
      conditions of waterlogged soils. On the other hand, emissions of hydrogen sulfide
      have been detected from many plant species. Since the amount of H2S discharged
      correlated with sulfate supply to the plants, the emissions were considered a
      mechanism for dissipation of excess sulfur. Significant hydrogen sulfide
      emissions were also observed in plants infected with pathogens, particularly with
      fungi. H2S thus seems to be part of the widely discussed sulfur-induced
      resistance/sulfur-enhanced-defense. Recently, however, more evidence has emerged
      for a role for H2S in regulation and signaling. Sulfide stabilizes the cysteine
      synthase complex, increasing so the synthesis of its acceptor O-acetylserine. H2S
      has been implicating in regulation of plant stress response, particularly draught
      stress. There are more and more examples of processes regulated by H2S in plants
      being discovered, and hydrogen sulfide is emerging as an important signaling
      molecule, similar to its role in the animal and human world. How similar the
      functions, and homeostasis of H2S are in these diverse organisms, however,
      remains to be elucidated. 

PMID- 24582857
TI  - Hydrogen sulfide and the liver.
AB  - Hydrogen sulfide (H2S) is a gasotransmitter that regulates numerous physiological
      and pathophysiological processes in our body. Enzymatic production of H2S is
      catalyzed by cystathionine gamma-lyase (CSE), cystathionine beta-synthase (CBS),
      and 3-mercaptopyruvate sulfurtransferase (MST). All these three enzymes present
      in the liver and via H2S production regulate liver functions. The liver is the
      hub for metabolism of glucose and lipids, and maintains the level of circulatory
      lipids through lipoprotein metabolism. Hepatic H2S metabolism affects glucose
      metabolism, insulin sensitivity, lipoprotein synthesis, mitochondrial biogenetics
      and biogenesis. Malfunction of hepatic H2S metabolism may be involved in many
      liver diseases, such as hepatic fibrosis and hepatic cirrhosis. 

PMID- 24582858
TI  - Serum dipeptidyl peptidase-IV: a better screening test for early detection of
      mucopolysaccharidosis?
AB  - We aimed to investigate the diagnostic utility of serum DPP-IV enzyme activity,
      urinary GAG/Cre ratio, chitotriosidase activity, total adenosine deaminase (ADA)
      and ADA-1 isoenzyme activity in the diagnosis of MPS. 31 MPS patients which were
      previously diagnosed by clinical and enzymatic analysis and 31 healthy controls
      matched with age and gender were included in this study. Serum DPP-IV enzyme
      activity, urinary GAG/Cre ratio, total ADA and ADA-1 isoenzyme activity were
      significantly higher in patients than in controls (p<0.001, p<0.001, p=0.038 and
      p=0.006, respectively). There were significant correlations between serum DPP-IV
      enzyme activity and urinary GAG/Cre ratios, ADA-1 activity, ADA-1/total ADA
      (r=0.498, p<0.001; r=0.348, p=0.006; r=0.270, p=0.034, respectively). Area under
      ROC curve for DPP-IV enzyme activity was 0.988, p<0.001 and for urinary GAG/Cre
      ratio was 0.986, p<0.001. DPP-IV enzyme activity and urinary GAG/Cre ratio were
      the most significant parameters according to the univariate logistic regression
      analysis (p=0.001 and p<0.001, respectively). The measurement of serum DPP-IV
      enzyme activity can be used complementary to the urinary GAG/Cre ratio for first
      line MPS screening, since it is more less prone to age and hydration related
      interferences. 

PMID- 24582859
TI  - Mononuclear cells in dementia.
AB  - According to the World Health Organization statistics, dementias are the largest
      contributors to disease burden in advanced market economies, and the leading
      cause of disability and dependence among older people worldwide. So far, several
      techniques have been developed to identify dementias with reasonable accuracy
      while the patient is still alive, however, no single of them has proven to be
      ideal, especially if you need to have a satisfactory early diagnosis. Studies of
      early onset dementia are largely limited by the inaccessibility to direct
      examination of the living human brain: it appears therefore that for a correct
      biochemical and molecular characterization of dementias, potential surrogate
      tissues must be identified. In this context, peripheral blood mononuclear cells
      (PBMCs) appear particularly attractive because they can be obtained in a
      minimally invasive manner and can be easily analyzed. This review focuses on the
      most representative methodologies and strategies in detecting and quantifying
      fluctuation in dementia that are currently being developed. In addition it
      provides a comprehensive evaluation of the diagnostic sensitivity of PBMCs in
      patients with dementia. Finally, it discusses the data supporting the use of the
      determination of neutral lipids (NLs) in PBMCs by Oil Red O (ORO) staining, which
      is a minimally invasive, cheap, easy and fast procedure, as the promising method
      for early detection of dementia and to search for new effective treatments. 

PMID- 24582860
TI  - Thyroid hormone induction of human cholesterol 7 alpha-hydroxylase (Cyp7a1) in
      vitro.
AB  - Thyroid hormone (TH) modulates serum cholesterol by acting on TH receptor beta1
      (TRbeta1) in liver to regulate metabolic gene sets. In rodents, one important TH
      regulated step involves induction of Cyp7a1, an enzyme in the cytochrome P450
      family, which enhances cholesterol to bile acid conversion and plays a crucial
      role in regulation of serum cholesterol levels. Current models suggest, however,
      that Cyp7a1 has lost the capacity to respond to THs in humans. We were prompted
      to re-examine TH effects on cholesterol metabolic genes in human liver cells by a
      recent study of a synthetic TH mimetic which showed that serum cholesterol
      reductions were accompanied by increases in a marker for bile acid synthesis in
      humans. Here, we show that TH effects upon cholesterol metabolic genes are almost
      identical in mouse liver, mouse and human liver primary cells and human
      hepatocyte cell lines. Moreover, Cyp7a1 is a direct TR target gene that responds
      to physiologic TR levels through a set of distinct response elements in its
      promoter. These findings suggest that THs regulate cholesterol to bile acid
      conversion in similar ways in humans and rodent experimental models and that
      manipulation of hormone signaling pathways could provide a strategy to enhance
      Cyp7a1 activity in human patients. 

PMID- 24582861
TI  - Basement membrane influences intestinal epithelial cell growth and presents a
      barrier to the movement of macromolecules.
AB  - This work examines the potential drug delivery barrier of the basement membrane
      (BM) by assessing the permeability of select macromolecules and nanoparticles.
      The study further extends to probing the effect of BM on intestinal epithelial
      cell attachment and monolayer characteristics, including cell morphology. Serum
      free cultured Caco-2 cells were grown on BM-containing porous supports, which
      were obtained by prior culture of airway epithelial cells (Calu-3), shown to
      assemble and deposit a BM on the growth substrate, followed by decellularisation.
      Data overall show that the attachment capacity of Caco-2 cells, which is
      completely lost in serum-free culture, is fully restored when the cells are grown
      on BM-coated substrates, with cells forming intact monolayers with high
      electrical resistance and low permeability to macromolecules. Caco-2 cells
      cultured on BM-coated substrates displayed strikingly different morphological
      characteristics, suggestive of a higher level of differentiation and closer
      resemblance to the native intestinal epithelium. BM was found to notably hinder
      the diffusion of macromolecules and nanoparticles in a size dependent manner.
      This suggests that the specialised network of extracellular matrix proteins may
      have a significant impact on transmucosal delivery of certain therapeutics or
      drug delivery systems. 

PMID- 24582862
TI  - Interleukin-8 promotes canine hemangiosarcoma growth by regulating the tumor
      microenvironment.
AB  - Interleukin-8 (IL-8) gene expression is highly up-regulated in canine
      hemangiosarcoma (HSA); however, its role in the pathogenesis of this disease is
      unknown. We investigated the expression of IL-8 in canine HSA tissues and cell
      lines, as well and the effects of IL-8 on canine HSA in vitro, and in vivo using
      a mouse xenograft model for the latter. Constitutive expression of IL-8 mRNA, IL
      8 protein, and IL-8 receptor were variable among different tumor samples and cell
      lines, but they showed stable steady states in each cell line. Upon the addition
      of IL-8, HSA cells showed transient intracellular calcium fluxes, suggesting that
      their IL-8 receptors are functional and that IL-8 binding activates relevant
      signaling pathways. Yet, neither addition of exogenous IL-8 nor blockade of
      endogenous IL-8 by neutralizing anti-IL-8 antibody (alpha-IL-8 Ab) affected HSA
      cell proliferation or survival in vitro. To assess potential effects of IL-8 in
      other tumor constituents, we stratified HSA cell lines and whole tumor samples
      into "IL-8 high" and "IL-8 low" groups. Genome-wide gene expression profiling
      showed that samples in the "IL-8 high" tumor group were enriched for genes
      associated with a "reactive microenvironment," including activation of
      coagulation, inflammation, and fibrosis networks. Based on these findings, we
      hypothesized that the effects of IL-8 on these tumors were mostly indirect,
      regulating interactions with the microenvironment. This hypothesis was supported
      by in vivo xenograft experiments where survival and engraftment of tumor cells
      was inhibited by administration of neutralizing alpha-IL-8 Ab. Together, our
      results suggest that IL-8 contributes to establishing a permissive
      microenvironment during the early stages of tumorigenesis in HSA. 

PMID- 24582863
TI  - The tick tock of odontogenesis.
AB  - Although a big deal of dental research is being focused to the understanding of
      early stages of tooth development, a huge gap exist on our knowledge on how the
      dental hard tissues are formed and how this process is controlled daily in order
      to produce very complex and diverse tooth shapes adapted for specific functions.
      Emerging evidence suggests that clock genes, a family of genes that controls
      circadian functions within our bodies, regulate also dental mineralized tissues
      formation. Enamel formation, for example, is subjected to rhythmical molecular
      signals that occur on short (24h) periods and control the secretion and
      maturation of the enamel matrix. Accordingly, gene expression and ameloblast
      functions are also tightly modulated in regular daily intervals. This review
      summarizes the current knowledge on the circadian controls of dental mineralized
      tissues development with a special emphasis on amelogenesis. 

PMID- 24582864
TI  - Role of neoadjuvant chemotherapy in the management of advanced ovarian yolk sac
      tumor.
AB  - OBJECTIVE: The aim of the study was to identify the role of neoadjuvant
      chemotherapy (NACT) in the treatment of the patients with advanced stage ovarian
      yolk sac tumor (OYST). METHODS: The comparative study was based on 53 cases with
      advanced stage OYST registered at Peking Union Medical College Hospital from 1995
      to 2010. Twenty one cases were treated with NACT followed by interval debulking
      surgery (IDS). Thirty two cases were treated with primary debulking surgery
      (PDS). Data on patient characteristics, treatment and survival were analyzed and
      compared between two groups to assess the outcome of NACT. RESULTS: After NACT,
      the overall status of the patients was improved significantly. Patients in NACT
      had better optimal cytoreduction rate and less peri-operative morbidities. Seven
      patients (13.2%) suffered from relapse. There was a significantly better PFS for
      patients with ovarian tumor size >20cm in the NACT than those underwent PDS.
      Residual disease >2cm was the independent risk factor of relapse. CONCLUSIONS:
      NACT is the better treatment option for some patients with advanced stage OYST,
      especially for those with unresectable tumors and poor general condition.

PMID- 24582865
TI  - Detection of sentinel lymph nodes in minimally invasive surgery using indocyanine
      green and near-infrared fluorescence imaging for uterine and cervical
      malignancies.
AB  - OBJECTIVES: Our primary objective was to assess the detection rate of sentinel
      lymph nodes (SLNs) using indocyanine green (ICG) and near-infrared (NIR)
      fluorescence imaging for uterine and cervical malignancies. METHODS: NIR
      fluorescence imaging for the robotic platform was obtained at our institution in
      12/2011. We identified all cases planned for SLN mapping using fluorescence
      imaging from 12/2011-4/2013. Intracervical ICG was the fluorophobe in all cases.
      Four cc (1.25mg/mL) of ICG was injected into the cervix alone divided into the 3-
      and 9-o'clock positions, with 1 cc deep into the stroma and 1 cc submucosally
      before initiating laparoscopic entry. Blue dye was concurrently injected in some
      cases. RESULTS: Two hundred twenty-seven cases were performed. Median age was 60
      years (range, 28-90 years). Median BMI was 30.2 kg/m(2) (range, 18-60 kg/m(2)).
      The median SLN count was 3 (range, 1-23). An SLN was identified in 216 cases
      (95%), with bilateral pelvic mapping in 179 (79%). An aortic SLN was identified
      in 21 (10%) of the 216 mapped cases. When ICG alone was used to map cases,
      188/197 patients mapped, for a 95% detection rate compared to 93% (28/30) in
      cases in which both dyes were used (P=NS). Bilateral mapping was seen in 156/197
      (79%) ICG-only cases and 23/30 (77%) ICG and blue dye cases (P=NS). CONCLUSIONS:
      NIR fluorescence imaging with intracervical ICG injection using the robotic
      platform has a high bilateral SLN detection rate and appears favorable to using
      blue dye alone and/or other modalities. Combined use of ICG and blue dye appears
      unnecessary.

PMID- 24582866
TI  - Acceptability of prophylactic salpingectomy with delayed oophorectomy as risk
      reducing surgery among BRCA mutation carriers.
AB  - OBJECTIVE: Given the emerging evidence for the fimbria as the site of origin for
      many serous carcinomas in BRCA mutation carriers, consideration is being given in
      studying prophylactic salpingectomy with delayed oophorectomy (PSDO) as a risk
      reducing surgery. We aimed to determine the interest in a study of PSDO among
      these women. METHODS: We evaluated the results of an online survey conducted by
      Facing Our Risk of Cancer Empowered (FORCE), a patient advocacy group, from
      October 2010 to August 2012. Premenopausal BRCA mutation carriers with no history
      of ovarian cancer or prior bilateral salpingo-oophorectomy (BSO) were included.
      RESULTS: Of the 204 women meeting inclusion criteria, median age was 35 years,
      92.5% were white, 25.7% were Jewish, and 16.7% had a history of breast cancer.
      Overall, 34.3% reported interest in a study of salpingectomy, 35.3% were unsure,
      and 30.4% were not interested in the study. Women noted the possibility of
      lowering ovarian cancer risk without menopause as a compelling reason to
      participate (83.8%). Reasons for not participating in a salpingectomy study
      included surgical complications (46.6%), potential ovarian damage (42.2%),
      planning BSO soon (32.4%), and surgical costs (32.8%). Acceptable study risks
      included the need for two surgeries (77.2%), possibility of not lowering ovarian
      cancer risk (68%), and disruption of ovarian blood supply (66.5%). CONCLUSIONS:
      One-third of BRCA mutation carriers indicated definite interest in a PSDO study.
      Potential study risks were acceptable to most women. These findings suggest that
      patient accrual for a clinical trial of prophylactic salpingectomy with delayed
      oophorectomy is possible.

PMID- 24582867
TI  - Relationship between minimally invasive hysterectomy, pelvic cytology, and lymph
      vascular space invasion: a single institution study of 458 patients.
AB  - OBJECTIVE: The aim of this study is to determine whether a minimally invasive
      approach to hysterectomy is associated with an increased rate of lymph vascular
      space invasion (LVSI) and/or malignant pelvic peritoneal cytology in endometrial
      cancer. METHODS: We performed a single institution analysis of 458 women with
      endometrial cancer who underwent either total abdominal hysterectomy (TAH) or
      minimally invasive hysterectomy (MIH) with use of a disposable uterine
      manipulator. All patients had endometrial cancer diagnosed by endometrial biopsy
      at a single academic institution between 2002 and 2012. Exclusion criteria were
      pre-operative D&C and/or hysteroscopy, uterine perforation or morcellation, and
      conversion to laparotomy. Multivariate logistic regression models to determine if
      type of hysterectomy predicts either LVSI or presence of abnormal cytology were
      controlled for grade, stage, depth of invasion, tumor size, cervical and adnexal
      involvement. RESULTS: LVSI was identified in 39/214 (18%) MIH and 44/242 (18%)
      TAH (p=0.99). Pelvic washings were malignant in 14/203 (7%) MIH and 16/241 (7%)
      TAH (p=1.0). Washings were atypical or inconclusive in 16/203 (8%) MIH and 6/241
      (2.5%) TAH (p=0.014). In multivariate analyses, type of hysterectomy was not a
      significant predictor of either LVSI (p=0.29) or presence of malignant washings
      (p=0.66), but was a predictor of atypical or inconclusive washings (p=0.03).
      CONCLUSION: Minimally invasive hysterectomy with use of a uterine manipulator for
      endometrial cancer is not associated with LVSI or malignant cytology. Algorithms
      that better determine the etiology and implications of inconclusive or atypical
      pelvic cytology are needed to inform the possible additional risk associated with
      a minimally invasive approach to endometrial cancer.

PMID- 24582868
TI  - Optical quality and intraocular scattering assessed with a double-pass system in
      eyes with contact lens induced corneal swelling.
AB  - PURPOSE: To evaluate the impact of contact lens (CL)-induced corneal swelling on
      the optical quality of the eye by means of the double-pass technique. METHODS:
      Measurements of 6 healthy subjects were obtained in 5 visits over 1 week, at
      baseline and after sleeping with 4 different CLs of +0.50 D, +2.00 D, +5.00 D and
      +8.00 D (Acuvue2), randomly fitted on 4 different days. The control eye wore no
      CL. Corneal pachymetry and optical quality of the eye (OQAS, Visiometrics) were
      measured once at baseline and at three interval times in the follow-up visits:
      immediately after CL removal, and 1 and 2 h after CL removal. Optical quality was
      evaluated by means of the Strehl ratio and OQAS values at 100%, 20% and 9%
      contrasts. Intraocular scattering was evaluated with the objective scatter index
      (OSI). RESULTS: Mean overnight swelling was 5.98 +/- 4.29% in CL-eyes versus 0.30
      +/- 0.78% in control eyes (p < 0.01). Corneal swelling was maximal immediately
      after CL removal and decreased with time (p < 0.01). A significant worsening in
      all optical quality parameters and a significant increase of the OSI were found
      in eyes with corneal swelling (p < 0.05). Two hours after CL removal there were
      no statistically significant differences (p > 0.05) between CL-eyes and control
      eyes in any of the measured parameters. CONCLUSIONS: Corneal swelling has a
      significant impact on the optical quality of the eye and on intraocular
      scattering as assessed with the double-pass technique.

PMID- 24582869
TI  - A case of concomitant keratoconus and granular corneal dystrophy type II.
AB  - PURPOSE: We report a Korean case of concomitant keratoconus and granular corneal
      dystrophy type II. METHODS: Case report. RESULTS: A 29-year-old man visited our
      clinic for a routine ocular check-up. Slit-lamp examination revealed a few well
      circumscribed, greyish-white, discrete granular opacities in the central corneal
      stromae of both eyes. Direct sequencing of exon 4 of the BIGH3 gene revealed a
      heterozygous transversion from G to A in the second-nucleotide position of codon
      124. In addition, a Fleischer ring and Vogt's striae were evident in the cornea.
      The corneal topography was suggestive of keratoconus. CONCLUSION: Granular
      corneal dystrophy type II can co-exist with keratoconus and should be included in
      the differential diagnosis.

PMID- 24582871
TI  - Benign episodic mydriasis. Experience in a specialist neuro-ophthalmology clinic
      of a tertiary hospital.
AB  - INTRODUCTION: Anisocorias are a relatively frequent reason for consultation in
      neuro-ophthalmology units. They remain a diagnostic challenge for specialists as
      they may be due to several etiological factors. In the absence of other
      accompanying symptoms, anisocorias are usually due to benign processes. Benign
      episodic mydriasis (BEM) is an isolated cause of intermittent pupil asymmetry, in
      which the pathophysiology is still not fully understood, and is predominant in
      young women with migraine. SUBJECTS, MATERIAL AND METHODS: We describe the
      epidemiological and clinical characteristics of patients with BEM, assessed in a
      neuro-ophthalmology unit in a tertiary hospital. RESULTS: A total of 7 patients
      were diagnosed with BEM, all of them females, with a mean age of 33 +/- 10 yrs.
      The patients presented with pupil asymmetry (n = 5) and blurred vision (n = 2),
      and 6 of the 7 patients had unilateral involvement. The duration of impairment
      varied from a few minutes to 48 hrs. Four patients (57%) had a clinical history
      of migraine without aura. The episodes in these 4 patients were recurrent (75%),
      often lasted for a few minutes (75%), and had associated blurred vision (50%).
      The neuroimaging studies were normal. DISCUSSION: BEM appears predominantly in
      young women. It is frequently related to a previous history of migraine, and the
      specialist must consider if it is a concomitant symptom of common migraine,
      migraine with aura, or ophthalmoplegic migraine. Although BEM has unilateral
      predominance, there may be alternation of the affected eye or even bilateral
      impairment during the same episode, which makes us question the adequacy of the
      term to describe the process. Imaging tests are not recommended in the absence of
      other accompanying symptoms, or in short-term episodes.

PMID- 24582872
TI  - Insights into drug discovery from natural medicines using reverse
      pharmacokinetics.
AB  - Natural medicines (NMs) are indispensable sources for the development of modern
      drugs. However, the targets for most natural compounds are unknown and the
      current pharmacokinetic evaluation systems developed for target-defined drugs may
      not be directly applicable to NM-based drug discovery, which is a major hindrance
      in bringing natural compounds to the clinic. Here, we propose the concept of
      'reverse pharmacokinetics' and discuss how a 'reverse pharmacokinetics'
      perspective could help clarify key questions in modern drug discovery from NMs
      with validated clinical benefits, thereby strengthening the translational
      potential. Reverse pharmacokinetics can provide physiologically relevant clues to
      the target identification and mechanistic study of NMs, which may also innovate
      drug discovery for complex diseases. We anticipate that an evolving deep
      understanding of the novel mode of action of natural compounds with a reverse
      pharmacokinetic insight may improve discovery of both single ingredient and
      multiple-component modern drugs from NMs. 

PMID- 24582873
TI  - Prevalence and factors associated with left ventricular remodeling in renal
      artery stenosis.
AB  - The objective of this study is to evaluate the prevalence, geometric patterns,
      and factors associated with left ventricular remodeling in patients with renal
      artery stenosis (RAS). Demographic, clinical, and echocardiographic data were
      assessed in 77 patients with RAS prior to endovascular stenting. The left
      ventricular mass index (LVMI) and relative wall thickness were calculated using
      American Society of Echocardiography (ASE) recommendations. Patients were
      classified based on LVMI and relative wall thickness into four ventricular
      remodeling patterns: normal geometry, concentric remodeling (CR), concentric
      hypertrophy (CH), and eccentric hypertrophy (EH). Logistic regression was done to
      investigate the determinants of the different ventricular remodeling patterns.
      Mean LVMI and relative wall thickness were 118 +/- 40 g/m(2) and 0.45 +/- 0.1.
      Left ventricular hypertrophy was observed in 65%. CH was the most prevalent
      geometric pattern of remodeling (normal, 16.9%; CR, 18.2%; CH, 40%; EH, 24.6%).
      Thirty (39%) patients had an abnormal LV systolic function (ejection fraction
      <55%), with 14 (46%) of them having eccentric hypertrophy. Independent predictor
      of EH was glomerular filtration rate (odds ratio [OR], 0.943; confidence interval
      [CI], 0.899-0.989; P = .01). Systolic elevation of blood pressure (OR, 1.030; CI,
      1.003-1.058; P = .03) was associated with CH, and elevated diastolic blood
      pressure was associated with CR (OR, 0.927; CI, 0.867-0.992; P = .02). Patients
      with RAS have a high prevalence of left ventricular remodeling and LVH. Even
      though CH was the most prevalent pattern of left ventricular remodeling, EH was
      commonplace and was associated with renal dysfunction and heart failure. 

PMID- 24582874
TI  - The relation of the cortisol awakening response and prospective memory
      functioning in young children.
AB  - Recent research suggests that the cortisol awakening response (CAR) is linked to
      cognitive functions depending on hippocampal and frontal cortex circuits and may
      possibly be modulated by prospective memory (PM). However, the link between the
      CAR and PM abilities has not been investigated so far. Addressing this open
      issue, we report data from 97 children aged 37-87 months. Salivary cortisol
      levels were assessed 0 and 30 min post-awakening over three study days. Thereby a
      valid CAR measurement was ensured by using objective measures of awakening and
      sampling times. A game-like task served as behavioral measure of PM performance.
      Bayesian analysis revealed a positive association between children's PM
      performance and the CAR, with better PM performance being related to a greater
      CAR. This association persisted after controlling for age. Overall, the current
      finding supports the prediction that PM functioning may be linked to the CAR,
      possibly as both the CAR and PM rely on a common neurophysiological basis.

PMID- 24582875
TI  - Bush Sophora Root polysaccharide and its sulfate can scavenge free radicals
      resulted from duck virus hepatitis.
AB  - In order to study the antioxidant effect of Bush Sophora Root polysaccharide
      (BSRPS) and its sulfate on anti-duck virus hepatitis (DVH), sulfated Bush Sophora
      Root polysaccharide (sBSRPS) was prepared by chlorosulfonic acid-pyridine method.
      Ducklings were fed with BSRPS and sBSRPS after challenged DHAV. Death was
      monitored, evaluation indexes of peroxidative and hepatic injury at the initial
      (4th and 8th hour) and later (54th hour) stages were detected. The results showed
      a fine treatment effect of BSRPS and sBSRPS. Visual hepatic pathological injury
      severities were less serious after the treatment. At the initial stage, free
      radical levels in all groups were the same, and BSRPS and sBSRPS reduced the
      hepatic injury through inhibiting virus replication. At the later stage, mass
      free radicals were detected in VC group while free radical levels in BSRPS and
      sBSRPS groups were significantly lower than VC group. The antioxidant effect of
      BSRPS and sBSRPS might alleviate the hepatic injury.

PMID- 24582876
TI  - Differences in adolescent relationship abuse perpetration and gender-inequitable
      attitudes by sport among male high school athletes.
AB  - PURPOSE: School-based athletic programs remain an important context for violence
      prevention efforts although a better understanding of how gender attitudes and
      abuse perpetration differ among athletes is needed. METHODS: We analyzed baseline
      survey data from the "Coaching Boys into Men" study-a school-based cluster
      randomized trial in 16 high schools in Northern California. We describe
      relationships among gender-inequitable attitudes, sport type, and recent
      adolescent relationship abuse perpetration among a sample of male athletes (n =
      1,648). RESULTS: Gender-inequitable attitudes (adjusted odds ratio (AOR), 3.26;
      95% confidence interval (CI), 2.56, 4.15), participation in both high school
      football and basketball (AOR, 2.08; 95% CI, 1.37, 3.18), and participation in
      football only (AOR, 1.50; 95% CI, 1.02, 2.22) emerged as independently associated
      with recent ARA perpetration. CONCLUSIONS: Findings warrant targeted violence
      prevention efforts among male high school athletes that incorporate discussions
      of gender attitudes and healthy relationships, especially among sports teams at
      greater risk of adolescent relationship abuse perpetration.

PMID- 24582877
TI  - Fecal microbiota transplantation in the treatment of Clostridium difficile
      infections.
AB  - In recent years, Clostridium difficile infections have become more frequent, more
      severe, more refractory to standard treatment, and more likely to recur. Current
      antibiotic treatment regimens for Clostridium difficile infection alter the
      normal gut flora, which provide colonization resistance against Clostridium
      difficile. Over the past few years, there has been a marked increase in the
      knowledge of the gut microbiota and its role in health maintenance and disease
      causation. This has, fortuitously, coincided with the use of a unique microbial
      replacement therapy, fecal microbiota transplantation, in the treatment of
      patients with multiple recurrent Clostridium difficile infections. We briefly
      review current knowledge of the gut microbiota's functions. We then review the
      indications for use of fecal microbiota transplantation in Clostridium difficile
      infection, the techniques employed, and results of treatment. Fecal microbiota
      transplantation has been shown to be efficacious for patients with multiply
      recurrent Clostridium difficile infections (reported cure rates of 90%), with an
      excellent short-term safety profile, and has been included in the American
      College of Gastroenterology treatment guidelines for this troublesome disease.

PMID- 24582878
TI  - The eye cannot see what the mind does not know: an unusual cause of deep venous
      thrombosis.

PMID- 24582879
TI  - To dig or not to dig.

PMID- 24582880
TI  - The consumption gene.

PMID- 24582881
TI  - Hookah, is it really harmless?
AB  - The hookah is a snuff smoking device whose origin dates back to the fifteenth
      century, has been used extensively in the Middle East in recent decades has
      become popular in Western culture countries, particularly in Americas and Europe.
      It has been reported that like other forms smoking tobacco, their use can lead to
      addiction also is used for inhaling and other addictive substances. Has also been
      considered a risk factor for various isolated diseases, including chronic
      obstructive pulmonary disease (COPD), different types of cancer, hemodynamic
      alterations, vascular disease, infectious diseases, among others. In pregnant
      women has been reported that there use condition a diminution on fetal growth and
      different diseases in the newborn. It was also mentioned that hookah smoke
      contains several toxic substances that can affect both, the primary and the
      passive smoker, so we did this review to determine the complications associated
      with its use. 

PMID- 24582882
TI  - [Maternal-fetal surgery for spina bifida: future perspectives].
AB  - Open spina bifida or myelomeningocele (MMC) is a frequent congenital abnormality
      (450 cases per year in France) associated with high morbidity. Immediate
      postnatal surgery is aimed at covering the exposed spinal cord, preventing
      infection, treating hydrocephalus with a ventricular shunt. MMC surgical
      techniques haven't achieved any major progress in the past decades. Numerous
      experimental and clinical studies have demonstrated the MMC "two-hit" hypothetic
      pathogenesis: a primary embryonic congenital abnormality of the nervous system
      due to a failure in the closure of the developing neural tube, followed by
      secondary damages of spinal cord and nerves caused by long-term exposure to
      amniotic fluid. This malformation frequently develops cranial consequences, i.e.
      hydrocephalus and Chiari II malformation, due to leakage of cerebrospinal fluid.
      After 30 years of research, a randomized trial published in February 2011 proved
      open maternal-fetal surgery (OMFS) for MMC to be a real therapeutic option.
      Comparing prenatal to postnatal surgery, it confirmed better outcomes of MMC
      children after a follow up of 2.5 years: enhancement of lower limb motor
      function, decrease of the degree of hindbrain herniation associated with the
      Chiari II malformation and the need for shunting. At 5 years of age, MMC children
      operated prenatally seems to have better neurocognitive, motor and bladder
      sphincter outcomes than those operated postnatally. However, risks of OMFS exist:
      prematurity for the fetus and a double hysterotomy at approximately 3-month
      interval for the mother. Nowadays, it seems crucial to inform parents of MMC
      patients about OMFS and to offer it in France. Future research will improve our
      understanding of MMC pathophysiology and evaluate long-term outcomes of OMFS.
      Tomorrow's prenatal surgery will be less invasive and more premature using
      endoscopic, robotic or percutaneous techniques. Beforehand, Achilles' heel of
      maternal-fetal surgery, i.e. preterm premature rupture of membranes, preterm
      labor and preterm birth, must be solved. 

PMID- 24582883
TI  - Pharmacological benefit of I(1)-imidazoline receptors activation and nuclear
      factor kappa-B (NF-kappaB) modulation in experimental Huntington's disease.
AB  - Huntington's disease (HD), a neurodegenerative disorder, is characterized by
      progressive motor dysfunction, emotional disturbances, dementia, weight loss and
      anxiety. The tremendous amount of research work is required to identify new
      pharmacological agents of therapeutic utility to combat this condition. This
      study investigates the effect of selective modulator of I1-imidazoline receptor
      (moxonidine) as well as nuclear factor kappa-B (NF-kappaB) (natrium diethyl
      dithio carbamate trihydrate-NDDCT) on 3-nitropropionic acid (3-NPA) induced
      experimental HD condition. 3-NPA was used to induce mitochondrial damage and
      associated HD symptoms in rats. Anxiety was assessed using Elevated plus maze-EPM
      and learning-memory was assessed using EPM and Morris water maze-MWM. Different
      biochemical estimations were used to assess brain striatum oxidative stress
      (lipid peroxide, superoxide dismutase and catalase), nitric oxide levels
      (nitrite/nitrate), cholinergic activity (brain striatum acetyl cholinesterase
      activity), and mitochondrial enzyme complex (I, II and IV) activities. 3-NPA has
      induced anxiety, impaired learning-memory with a reduction in body weight,
      locomotor activity, grip strength. It has increased brain striatum
      acetylcholinesterase-AChE activity, oxidative stress (lipid peroxide,
      nitrite/nitrate, superoxide dismutase and catalase) and impaired mitochondrial
      complex enzyme (I, II and IV) activities. Tetrabenazine-TBZ (monoamine storage
      inhibitor) was used as positive control. Treatment with moxonidine, NDDCT and TBZ
      significantly attenuated 3-NPA induced reduction in body weight, locomotor
      activity, grip strength, anxiety as well as impaired learning and memory.
      Administration of these agents attenuated 3-NPA induced various biochemical
      impairments. Therefore, modulation of I1-imidazoline receptor as well as NF
      kappaB may be considered as potential pharmacological agents for the management
      of 3-NPA induced HD. 

PMID- 24582885
TI  - GALNT2 enhances migration and invasion of oral squamous cell carcinoma by
      regulating EGFR glycosylation and activity.
AB  - OBJECTIVES: Oral squamous cell carcinoma (OSCC) is one of the leading cancers
      worldwide. Aberrant glycosylation affects many cellular properties in cancers,
      including OSCC. This study aimed to explore the role of N
      acetylgalactosaminyltransferase 2 (GALNT2) in OSCC. MATERIALS AND METHODS:
      Immunohistochemistry was performed to study the expression of GALNT2 in an OSCC
      tissue microarray. Effects of GALNT2 overexpression and knockdown on cell
      migration and invasion were analyzed in SAS cells by transwell migration assay
      and matrigel invasion assay, respectively. The Vicia villosa agglutinin (VVA)
      pull down assay was conducted to detect changes in O-glycans on acceptor
      substrates of GALNT2. Cell signaling was analyzed by Western blotting. RESULTS:
      GALNT2 was overexpressed in 73% (35/48) of OSCC tissues. Moreover, GALNT2
      expression was localized in the invasive front and increased in high grade OSCC.
      GALNT2 overexpression enhanced migration and invasion of SAS cells triggered by
      fetal bovine serum (FBS) and epidermal growth factor (EGF). In contrast, GALNT2
      knockdown inhibited SAS cell migration and invasion. Furthermore, GALNT2
      overexpression enhanced VVA binding to epidermal growth factor receptor (EGFR)
      and EGF-induced phosphorylation of EGFR and AKT. Conversely, GALNT2 knockdown
      decreased VVA binding and suppressed activity of EGFR and AKT. CONCLUSION: GALNT2
      is frequently overexpressed in OSCC, especially in the carcinoma cells at the
      invasive front. GALNT2 overexpression enhances the invasive potential of OSCC
      cells via modifying O-glycosylation and activity of EGFR. These findings suggest
      that GALNT2 plays an important role in the invasive behavior of OSCC and that
      targeting GALNT2 could be a promising approach for OSCC therapy.

PMID- 24582884
TI  - Inhibitors of NF-kappaB reverse cellular invasion and target gene upregulation in
      an experimental model of aggressive oral squamous cell carcinoma.
AB  - BACKGROUND: Oral squamous cell carcinoma (OSCC) is diagnosed in 640,000 patients
      yearly with a poor (50%) 5-year survival rate that has not changed appreciably in
      decades. PAITENTS AND METHODS: To investigate molecular changes that drive OSCC
      progression, cDNA microarray analysis was performed using human OSCC cells that
      form aggressive poorly differentiated tumors (SCC25-PD) in a murine orthotopic
      xenograft model compared to cells that produce well-differentiated tumors (SCC25
      WD). RESULTS: As this analysis revealed that 59 upregulated genes were NF-kappaB
      target genes, the role of NF-kappaB activation in alteration of the
      transcriptional profile was evaluated. The mRNA and protein upregulation of a
      panel NF-kappaB target genes was validated by real-time qPCR and
      immunohistochemistry. Additionally, nuclear translocation of RelA was greatly
      increased in SCC25-PD, increased nuclear RelA was observed in oral tumors
      initiated with SCC25-PD compared with tumors initiated by SCC25-WD, and nuclear
      RelA correlated with stage of disease on two human OSCC tissue microarrays.
      Treatment of SCC25-PD cells with the IKKbeta-inhibitor sc-514, that effectively
      prevents RelA phosphorylation on Ser 536, reversed nuclear-translocation of RelA
      and strongly inhibited NF-kappaB gene activation. Furthermore, blocking the
      phosphorylation of RelA using the MSK1/2 inhibitor SB 747651A significantly
      reduced the mRNA upregulation of a subset of target genes. Treatment with sc-514
      or SB747651A markedly diminished cellular invasiveness. CONCLUSIONS: These
      studies support a model wherein NF-kappaB is constitutively active in aggressive
      OSCC, while blocking the NF-kappaB pathway reduces NF-kappaB target gene
      upregulation and cellular invasiveness.

PMID- 24582886
TI  - Neuroepigenetic disorders: progress, promises and challenges.

PMID- 24582887
TI  - Mitochondria: mitochondrial participation in ischemia-reperfusion injury in
      skeletal muscle.
AB  - Irrespective of the organ involved, restoration of blood flow to ischemic tissue
      is vital, although reperfusion per se is deleterious. In the setting of vascular
      surgery, even subtle skeletal muscle ischemia contributes to remote organ
      injuries and perioperative and long-term morbidities. Reperfusion-induced injury
      is thought to participate in up to 40% of muscle damage. Recently, the
      pathophysiology of lower limb ischemia-reperfusion (IR) has been largely
      improved, acknowledging a key role for mitochondrial dysfunction mainly
      characterized by impaired mitochondrial oxidative capacity and premature
      mitochondrial permeability transition pore opening. Increased oxidative stress
      triggered by an imbalance between reactive oxygen species (ROS) production and
      clearance, and facilitated by enhanced inflammation, appears to be both followed
      and instigated by mitochondrial dysfunction. Mitochondria are both actors and
      target of IR and therapeutic strategies modulating degree of ROS production could
      enhance protective signals and allow for mitochondrial protection through a
      mitohormesis mechanism. 

PMID- 24582888
TI  - Potentiation of Tbx5-mediated transactivation by SUMO conjugation and protein
      inhibitor of activated STAT 1 (PIAS1).
AB  - The role of the T-box transcription factor Tbx5 in heart and limb development has
      been well documented; however, how posttranslational modification is involved in
      mediating its activity is unknown. Here we report that Tbx5 is a novel target by
      SUMO conjugation, a posttranslational modification that is involved in a variety
      of cellular events. Sumoylation potentiated the transcriptional activity of Tbx5,
      and PIAS family members, a group of SUMO E3 ligase, differentially mediated
      sumoylation and function of Tbx5. PIAS1 potently stimulated SUMO conjugation to
      Tbx5, and the physical association of Tbx5 with PIAS1 was required for its full
      sumoylation. PIAS1 also enhanced the functional cooperation between Tbx5 and its
      interaction partners. Overlapping expression pattern and colocalization of PIAS1
      and Tbx5 in the mouse embryonic hearts and on the native target gene promoter
      were observed, pointing to a potential functional interaction of these two
      factors in vivo. These findings provide novel insights into how the
      transcriptional activity of a cardiac-specific factor, Tbx5, is regulated both
      directly and indirectly via posttranslational modification by a non-tissue
      specific factor, PIAS1. 

PMID- 24582889
TI  - Characterization of a novel CC chemokine CCL4 in immune response induced by
      nitrite and its expression differences among three populations of Megalobrama
      amblycephala.
AB  - A novel CC chemokine gene, chemokine CC motif ligand 4 (CCL4), was isolated from
      Megalobrama amblycephala. The full-length cDNA was 913 bp, encoding 94 amino acid
      residues. The deduced amino acid sequence possessed the typical arrangement of
      four cysteines as found in other known CC chemokines. The expression of M.
      amblycephala CCL4 during the early development showed the mRNA levels before
      hatching and at 62 h post fertilized (hpf) were significantly higher than other
      post-hatching stages (P < 0.05). Besides, it was widely expressed in all detected
      tissues with the highest transcription in liver, followed by intestine, spleen
      and gill, where a larger number of immune cells including lymphocytes and
      macrophages are present. Our findings had fully confirmed that CCL4 expression
      was strongly induced in vitro and quickly up-regulated after nitrite stress, then
      substantially altered in all tested tissues, supporting a potential pro
      inflammatory function. We also indicated that inflammation effect might firstly
      happen in blood after nitrite stress. Furthermore, the tissue expression
      differences of CCL4 among three natural populations revealed that CCL4 mRNA in
      Yuni Lake population was obviously higher than the other two populations, Liangzi
      Lake population and Poyang Lake population, which will provide valuable insights
      into breeding strategies for selecting population with better immune property of
      M. amblycephala.

PMID- 24582890
TI  - Effects of activated omental cells on rat limbal corneal alkali injury.
AB  - Omental cells (OCs) are shown to help wound healing. The purpose of this study is
      to investigate if OCs improve cornea repair after alkali injury by
      subconjunctival injection of activated OCs in rats. Forty eight hours after
      limbal corneal alkali injury, fresh isolated OCs were injected subconjunctivally
      into the recipient rat's eye. Prior to the injury and at 0, 4 and 8 days after
      injury, the eyes were examined using slit lamp biomicroscopy. Corneal
      opacification and corneal neovascularization were graded in a masked fashion. The
      inflammatory response to the injury was evaluated by counting neutrophil cell
      numbers in the cornea under microscope. There was no significant difference in
      corneal opacification between the control and OCs treatment groups; however, the
      corneal neovascularization was significantly less in the eyes treated with OCs as
      compared to the controls. Also OCs treatment markedly decreased neutrophil
      infiltration after corneal-limbal alkali injury. Our results suggest that OCs may
      have a beneficial role in corneal healing after limbal corneal alkali injury by
      suppressing inflammatory cell infiltrates and corneal neovascularization. 

PMID- 24582891
TI  - Soluble opsin is present in human vitreous.
AB  - The purpose of this research project was to evaluate if intravitreal opsins are
      present in human vitreous liquid which is, so far, unknown. Therefore a pilot
      study was conducted including 22 vitreal samples which were harvested at the
      beginning of a standard 23-gauge three-port pars plana vitrectomy for macular
      pucker, diabetic vitreous hemorrhage or vitreal floater removal as well as
      macular hole closure or vitreomacular traction relief from the central vitreous
      body. No adverse events or serious side effects occurred. All samples were
      immediately stabilized by human albumin and arginine and subsequently frozen.
      Short-wavelength cone opsin concentrations were analyzed by enzyme immune essay
      (EIA) with anti-proteolytic 400 mM arginine, pH 8.7, in the antigen capture
      phase. Intravitreal short-wavelength cone opsins were detected in all analyzed
      samples and respective concentrations ranged at levels of 157 pg/ml +/- 73 pg/ml
      (MV +/- SD; range: 27 pg/m-286 pg/ml). Eyes with MP/MH/DVH/VMT and VF exhibited
      intravitreal short-wavelength cone opsin concentrations of 189 pg/ml +/- 68 pg/ml
      (range: 72 pg/ml-286 pg/ml)/96 pg/ml +/- 39 pg/ml (range: 50 pg/ml-138 pg/ml)/126
      pg/ml +/- 88 pg/ml (range: 27 pg/ml-198 pg/ml)/224 pg/ml and 121 pg/ml. Further
      studies will quantify the intravitreal opsin pattern of all visual opsins and
      compare these concentrations between different vitreoretinal diseases. This in
      turn might offer a better pathophysiological understanding and new diagnostic and
      therapeutic strategies for various eye pathologies. As a hypothesis, soluble
      opsins might be a biomarker for retinal damage comparable to creatinine for
      kidney damage. 

PMID- 24582893
TI  - Biotransport and intracellular ice formation phenomena in freezing human
      embryonic kidney cells (HEK293T).
AB  - The objective of this study is to determine the cryobiological characteristics of
      human embryonic kidney (HEK293T) cells. The cell membrane hydraulic conductivity
      (L(pg)) and the activation energy of water transport (E(Lp)) were determined in
      the absence/presence of cryoprotectant agent (CPA), while the nucleation rate
      kinetic and thermodynamic parameters (Omegao(SCN) and kappao(SCN)) were
      determined in the absence of CPA. Since dehydration and intracellular ice
      formation (IIF) are two factors that may cause damage to cells during the
      freezing process, systematical freezing experiments were carried out at different
      cooling rates (5, 10, 15, 20, 30, and 60 degrees C/min) under the commercial
      available cryomicroscopy (FDCS 196, Linkham, Waterfield, UK) to further explore
      the cryoinjury mechanism for HEK293T cells. By simultaneously fitting the water
      transport equation to the experimentally measured volumetric shrinkage data at 5,
      10, and 15 degrees C/min, the "combined best fit" membrane permeability
      parameters for HEK293T cells in both phosphate buffer saline (PBS) and CPA media
      (0.75M Me2SO in PBS) are determined. They are L(pg)=2.85*10(-14)m/s/Pa
      (0.17MUm/min/atm), E(Lp)=142.91kJ/mol (34.13kcal/mol) (R(2)=0.990), and
      L(pg)[cpa]=2.73+/-0.44*10(-14)m/s/Pa (0.16+/-0.03MUm/min/atm),
      E(Lp)[cpa]=152.52+/-27.69kJ/mol (36.42+/-6.61kcal/mol) (R(2)=0.993),
      respectively. An optimal cooling rate B(opt) (the highest cooling rate without
      IIF) was determined to be 14.24 degrees C/min in the absence of CPA.
      Additionally, the ice nucleation parameters (Omegao(SCN) and kappao(SCN)) were
      averaged to be 1.31+/-0.11*10(8)m(-2)s(-1) and 7.67+/-2.55*10(9)K(5) for the
      cooling rates 20, 30, and 60 degrees C/min.

PMID- 24582892
TI  - TGFbeta and PDGF-B signaling blockade inhibits myofibroblast development from
      both bone marrow-derived and keratocyte-derived precursor cells in vivo.
AB  - Myofibroblasts, the primary cells associated with corneal stromal haze (opacity),
      can be derived from both cornea-derived and bone marrow-derived precursor cells.
      In the present study, the role of TGFbeta or PDGF blockage on bone marrow-derived
      myofibroblast development was investigated using a green fluorescent protein
      (GFP) chimeric bone marrow mouse model and plasmid vectors that blocked TGFbeta
      or PDGF signaling. At the peak of corneal haze one month after irregular
      phototherapeutic keratectomy the central stroma had significantly less alpha
      smooth muscle actin (alpha-SMA)-positive cells derived from GFP+ bone marrow
      derived cells or GFP- keratocyte/corneal fibroblast-derived cells when corneas
      were treated with the TGFbeta blocking vector pGFPC1.TGFRBKDEL or the PDGF
      blocking vector pCMV.PDGFRB.23KDEL compared with the corresponding empty vector
      treated or untreated control groups. In individual animals, 30-60% of
      myofibroblasts were derived from bone marrow-derived precursor cells and 40-70%
      of myofibroblasts were derived from keratocyte-derived precursor cells. TGFbeta
      and PDGF regulate corneal myofibroblast development from bone marrow-derived
      precursor cells and keratocyte/corneal fibroblast-derived precursor cells. 

PMID- 24582894
TI  - The potential antidepressant and antidiabetic effects of galanin system.
AB  - Epidemiological and clinical studies demonstrated that type 2 diabetes mellitus
      and depression are interconnected. Depression is an important risk factor for the
      development of type 2 diabetes mellitus, while patients with type 2 diabetes
      mellitus frequently have depressive symptoms. Despite many studies recently
      probed into the comorbid state of both diseases, so far the precise mechanism for
      this association is poorly understood. Experiments have demonstrated that
      neuropeptide galanin is involved in the pathogenesis of depression and type 2
      diabetes mellitus. This review provides a new insight into the multivariate
      relationship among galanin, depression and type 2 diabetes mellitus, highlighting
      the effect of galanin system on the cross-talk between both diseases in human and
      rodent models. The current data support that activating central GalR2 attenuates
      insulin resistance and depressive feature in animal models. These may help us
      better understand the pathogenesis of both diseases and provide useful hints for
      the development of novel therapeutic approaches, i.e. to coadministrate GalR2
      agonist with traditional antidepressive and antidiabetic medicines to treat
      depression and type 2 diabetes mellitus.

PMID- 24582895
TI  - Evaluation of student nurses' perception of preparedness for oral medication
      administration in clinical practice: a collaborative study.
AB  - BACKGROUND: Attainment of oral medication administration skills and competency
      for student nurses is challenging and medication errors are common. The ability
      of nurses to master a clinical skill is dependent upon educational instruction
      and practice. OBJECTIVES: The aim of this study was to evaluate nursing students'
      perception of preparedness for oral medication administration in two practice
      environments and determine possible relationship between student demographics and
      their perceived preparedness for oral medication administration. DESIGN: This was
      a cross sectional, exploratory study. PARTICIPANTS: Eighty-eight second year
      students from a baccalaureate nursing course from two metropolitan Australian
      tertiary institutions participated. METHODS: Student nurses' perception of
      preparedness for oral medication administration was measured via a self
      administered, adapted, and validated questionnaire. RESULTS: The overall mean
      Total Preparedness Score was 86.2 (range 71-102). There was no significant
      difference for perceived total preparedness to administer oral medications
      between the two facilities. Whilst there was no significant relationship
      established between student demographics and their perceived preparedness to
      administer oral medications, four single questions related to clinical practice
      were shown to be significant. CONCLUSION: Low fidelity simulated teaching
      environments that incorporate time management and post medication situations, may
      improve student nurses' perceived preparedness for oral medication
      administration.

PMID- 24582897
TI  - A novel presenilin 1 mutation (Ala275Val) as cause of early-onset familial
      Alzheimer disease.
AB  - Mutations in the presenilin 1 (PS1) gene (PSEN1) are associated with familial
      Alzheimer disease (FAD). Here, we report on a 50-year-old patient presenting with
      progressive deterioration of his short-term memory and a family history of early
      onset dementia. Diagnostic workup included a neuropsychological examination,
      structural magnetic resonance (MR) imaging, cerebrospinal fluid (CSF) biomarkers
      including total tau, phosphorylated tau, and Abeta42 levels, as well as
      sequencing relevant fragments of the genes PSEN1, PSEN2, and APP. Additionally,
      we were able to obtain archival paraffin-embedded cerebellar tissue from the
      patient's father for cosegregation analysis. Clinical, neuropsychological and MR
      imaging data were indicative of early-onset Alzheimer disease. Furthermore, CSF
      biomarkers showed a typical pattern for Alzheimer disease. DNA sequencing
      revealed a heterozygous nucleotide transition (c.824C>T) in exon 8 of PSEN1,
      leading to an amino acid change from alanine to valine at codon 275 (Ala275Val).
      The same mutation was found in an archival brain specimen of the patient's
      demented father, but not in a blood sample of the non-demented mother. This
      mutation alters a conserved residue in the large hydrophilic loop of PS1,
      suggesting pathogenic relevance. Cosegregegation analysis and the structural as
      well as the presumed functional role of the mutated and highly conserved residue
      suggest FAD causing characteristics of the novel PSEN1 mutation Ala275Val. 

PMID- 24582896
TI  - Evaluation of a discharge education protocol for pediatric patients with
      gastrostomy tubes.
AB  - INTRODUCTION: To evaluate the impact of a preprocedure education protocol for
      children who receive a gastrostomy tube (GT). METHODS: A preintervention
      postintervention design, using surveys and comparison between preprotocol and
      postprotocol cohorts, was used to evaluate the effect of implementation of a
      standardized GT education protocol with 26 subjects on caregiver, patient, and
      provider outcomes. RESULTS: The use of a preprocedure education protocol resulted
      in improved patient outcomes and increased caregiver knowledge and confidence and
      was considered a positive change by the providers. DISCUSSION: Often education is
      a forgotten part of a medical procedure, and the importance of education is
      typically only recognized after an adverse event occurs. Establishing a
      standardized evidence-based education protocol for GT care improves overall care
      and satisfaction. Use of a systematic and family-centered interdisciplinary
      approach markedly improves patient care.

PMID- 24582898
TI  - MUC4 modulates human glioblastoma cell proliferation and invasion by upregulating
      EGFR expression.
AB  - Glioblastoma (GBM), the most common primary brain tumor, is the leading cause of
      deaths related to tumors in the central nervous system. The prognosis of GBM
      patients is currently poor, and the mechanisms underlying GBM genesis remain
      unclear. The expression of MUC4, a high-molecular-weight and highly glycosylated
      protein, has been studied in many cancers. However, information on MUC4
      expression in GBM is limited. In this study, we found that MUC4 was overexpressed
      in GBM cell lines and tissues. The proliferation and invasive potential of GBM
      cells were significantly increased by the ectopic expression of MUC4. By
      contrast, RNA interference targeting MUC4 in GBM cells significantly decreased
      the proliferation and invasive potential of GBM cells. We also found that the
      expression of epidermal growth factor receptor (EGFR) was modulated by MUC4. EGFR
      inhibition by siRNA reversed the MUC4-induced proliferation and invasion. These
      results indicated that MUC4 expression in GBM was important in GBM cell
      proliferation and invasion, which may be partly associated with EGFR
      overexpression. 

PMID- 24582899
TI  - Explicit and implicit knowledge of environment states induce adaptation in
      postural control.
AB  - The aim of this study was to investigate the effects of explicit and implicit
      knowledge about visual surrounding manipulation on postural responses. Twenty
      participants divided into two groups, implicit and explicit, remained in upright
      stance inside a "moving room". In the fourth trial participants in the explicit
      group were informed about the movement of the room while participants in the
      implicit group performed the trial with the room moving at a larger amplitude and
      higher velocity. Results showed that postural responses to visual manipulation
      decreased after participants were told that the room was moving as well as after
      increasing amplitude and velocity of the room, indicating decreased coupling
      (down-weighting) of the visual influences. Moreover, this decrease was even
      greater for the implicit group compared to the explicit group. The results
      demonstrated that conscious knowledge about environmental state changes the
      coupling to visual information, suggesting a cognitive component related to
      sensory re-weighting. Re-weighting processes were also triggered without
      awareness of subjects and were even more pronounced compared to the first case.
      Adaptive re-weighting was shown when knowledge about environmental state was
      gathered explicitly and implicitly, but through different adaptive processes. 

PMID- 24582900
TI  - Effect of handball training on cognitive ability in elderly with mild cognitive
      impairment.
AB  - The aim was to examine the effect of handball training on cognitive ability in
      elderly with mild cognitive impairment. A total of 60 elderly were randomly
      divided into training group (n=30) and control group (n=30). The mini-mental
      state examination (MMSE) score and abilities of daily living scale (ADL) score
      before, after 3-month, and after 6-month intervention period was measured. The
      results showed that MMSE score was increased and ADL score was decreased in
      training group after 3-month and 6-month intervention (P<0.05), while there were
      no significant changes in MMSE or ADL in control group (PL3/40.05). These
      preliminary results indicated that handball training can improve cognitive
      ability in elderly with MCI. 

PMID- 24582901
TI  - Differences between musicians and non-musicians in neuro-affective processing of
      sadness and fear expressed in music.
AB  - Music is known to convey and evoke emotional states. Musical training has been
      argued to lead to changes in neural architecture and enhanced processing of
      emotions. It is not clear, however, whether musical training is also associated
      with changes in behavioral and neural responses to musically conveyed discrete
      emotions. Using functional magnetic resonance imaging, we investigated the
      responses to three musically conveyed emotions (happiness, sadness, fear) in a
      group of musicians and a group of non-musicians. We find that musicians rate
      sadness and fear as significantly more arousing than non-musicians, and that
      musical training is associated with specific neural activations: In response to
      sadness expressed in music, musicians show activation increases in the right
      prefrontal cortex, specifically in the superior and middle frontal gyri. In
      response to fear, musicians show activation increases in the right parietal
      cortex, specifically in the supramarginal and inferior parietal gyri. No specific
      activations were observed in response to happiness. Our results highlight the
      strong association between musical training and altered processing of "negative"
      emotions on both the behavioral and on the neural level. 

PMID- 24582902
TI  - Ferulic acid attenuates the cerebral ischemic injury-induced decrease in
      peroxiredoxin-2 and thioredoxin expression.
AB  - Ferulic acid, a phenolic phytochemical compound found in various plants, has a
      neuroprotective effect through its anti-oxidant and anti-inflammation functions.
      Peroxiredoxin-2 and thioredoxin play a potent neuroprotective function against
      oxidative stress. We investigated whether ferulic acid regulates peroxiredoxin-2
      and thioredoxin levels in cerebral ischemia. Sprague-Dawley rats (male, 210-230g)
      were treated with vehicle or ferulic acid (100mg/kg) after middle cerebral artery
      occlusion (MCAO), and cerebral cortex tissues were collected 24h after MCAO.
      Decreases in peroxiredoxin-2 and thioredoxin levels were elucidated in MCAO
      operated animals using a proteomics approach. We found that ferulic acid
      treatment prevented the MCAO-induced decrease in the expression of peroxiredoxin
      2 and thioredoxin. RT-PCR and Western blot analyses confirmed that ferulic acid
      treatment attenuated the MCAO-induced decrease in peroxiredoxin-2 and thioredoxin
      levels. Moreover, immunoprecipitation analysis showed that the interaction
      between thioredoxin and apoptosis signal-regulating kinase 1 (ASK1) decreased
      during MCAO, whereas ferulic acid prevented the MCAO-induced decrease in this
      interaction. Our findings suggest that ferulic acid plays a neuroprotective role
      by attenuating injury-induced decreases in peroxiredoxin-2 and thioredoxin levels
      in neuronal cell injury. 

PMID- 24582903
TI  - Entrainment of spontaneous cerebral hemodynamic oscillations to behavioral
      responses.
AB  - Entrainment in physiological systems can be manifest in cases where phase
      coupling (synchronization) between slow intrinsic oscillations and periodic motor
      responses, or vice versa, takes place. To test whether voluntary movement has
      something in common with entrainment of slow hemodynamic oscillations to motor
      responses, we studied blood pressure (BP), heart rate beat-to-beat intervals
      (RRI) and prefrontal (de)oxyhemoglobin (Hb/HbO2) during 5min of rest, 10min of
      self-paced, voluntary movements and 10min of stimulus-paced movements at 10s
      intervals in 9 subjects. Subjects were divided into 2 groups according to the
      timing of voluntary finger movements. It appeared that these movements occurred
      at relatively regular intervals of approximately 10s in 5 subjects (group A);
      while 4 subjects showed random or very short inter-movement intervals (group B).
      Two remarkable results were obtained: first, the phase coupling (COH(2)) between
      BP and RRI showed a significant (p=0.0061) interaction between activity (rest vs.
      movement) and group (A vs. B), with an increased (p=0.0003) coupling in group A.
      Second, the COH(2) between BP and Hb oscillations showed a significant (p=0.034)
      interaction between activity and group, with a decreased (p=0.079) coupling in
      group B. These results suggest that subjects able to initiate self-paced,
      voluntary movements at relatively regular intervals of ~10s show an entrainment
      potential between physiological oscillations and motor responses. This also
      provides the first evidence that not only physiological oscillations can be
      entrained to motor responses, but also motor responses (voluntary movements) can
      be entrained to slow intrinsic oscillations. 

PMID- 24582905
TI  - Similar ventral occipito-temporal cortex activations in literate and illiterate
      adults during the Chinese character matching task: an fMRI study.
AB  - Visual word expertise is typically associated with enhanced ventral occipito
      temporal (vOT) cortex activation in response to written words. Previous study
      utilized a passive viewing task and found that vOT response to written words was
      significantly stronger in literate compared to the illiterate subjects. However,
      recent neuroimaging findings have suggested that vOT response properties are
      highly dependent upon the task demand. Thus, it is unknown whether literate
      adults would show stronger vOT response to written words compared to illiterate
      adults during other cognitive tasks, such as perceptual matching. We addressed
      this issue by comparing vOT activations between literate and illiterate adults
      during a Chinese character and simple figure matching task. Unlike passive
      viewing, a perceptual matching task requires active shape comparison, therefore
      minimizing automatic word processing bias. We found that although the literate
      group performed better at Chinese character matching task, the two subject groups
      showed similar strong vOT responses during this task. Overall, the findings
      indicate that the vOT response to written words is not affected by expertise
      during a perceptual matching task, suggesting that the association between visual
      word expertise and vOT response may depend on the task demand. 

PMID- 24582904
TI  - PTEN inhibitor bisperoxovanadium protects oligodendrocytes and myelin and
      prevents neuronal atrophy in adult rats following cervical hemicontusive spinal
      cord injury.
AB  - Cervical spinal cord injury (SCI) damages axons and motor neurons responsible for
      ipsilateral forelimb function and causes demyelination and oligodendrocyte death.
      Inhibition of the phosphatase and tensin homologue, PTEN, promotes neural cell
      survival, neuroprotection and regeneration in vivo and in vitro. PTEN inhibition
      can also promote oligodendrocyte-mediated myelination of axons in vitro likely
      through Akt activation. We recently demonstrated that acute treatment with
      phosphatase PTEN inhibitor, bisperoxovanadium (bpV)-pic reduced tissue damage,
      neuron death, and promoted functional recovery after cervical hemi-contusion SCI.
      Evidence suggests bpV can promote myelin stability; however, bpV effects on
      myelination and oligodendrocytes in contusive SCI models are unclear. We
      hypothesized that bpV could increase myelin around the injury site through
      sparing or remyelination, and that bpV treatment may promote increased numbers of
      oligodendrocytes. Using histological and immunofluorescence labeling, we found
      that bpV treatment promoted significant spared white matter (30%; p<0.01) and
      relative Luxol Fast Blue (LFB)(+) myelin area rostral (Veh: 0.56 +/- 0.01 vs.
      bpV: 0.64 +/- 0.02; p<0.05) and at the epicenter (Veh: 0.42 +/- 0.03 vs. bpV:
      0.54 +/- 0.03; p<0.05). VLF oligodendrocytes were also significantly greater with
      bpV therapy (109 +/- 5.3 vs. Veh: 77 +/- 2.7 mm(-2); p<0.01). In addition, bpV
      increased mean motor neuron soma area versus vehicle-treatment (1.0 +/- 0.02 vs.
      Veh: 0.77 +/- 0.02) relative to Sham neuron size. This study provides key insight
      into additional cell and tissue effects that could contribute to bpV-mediated
      functional recovery observed after contusive cervical SCI.

PMID- 24582906
TI  - Is the size of the useful field of view affected by postural demands associated
      with standing and stepping?
AB  - The useful field of view (UFOV) is the visual area from which information is
      obtained at a brief glance. While studies have examined the effects of increased
      cognitive load on the visual field, no one has specifically looked at the effects
      of postural control or locomotor activity on the UFOV. The current study aimed to
      examine the effects of postural demand and locomotor activity on UFOV performance
      in healthy young adults. Eleven participants were tested on three modified UFOV
      tasks (central processing, peripheral processing, and divided-attention) while
      seated, standing, and stepping in place. Across all postural conditions,
      participants showed no difference in their central or peripheral processing.
      However, in the divided-attention task (reporting the letter in central vision
      and target location in peripheral vision amongst distracter items) a main effect
      of posture condition on peripheral target accuracy was found for targets at 57
      degrees  of eccentricity (p=.037). The mean accuracy reduced from 80.5%
      (standing) to 74% (seated) to 56.3% (stepping). These findings show that postural
      demands do affect UFOV divided-attention performance. In particular, the size of
      the useful field of view significantly decreases when stepping. This finding has
      important implications for how the results of a UFOV test are used to evaluate
      the general size of the UFOV during varying activities, as the traditional seated
      test procedure may overestimate the size of the UFOV during locomotor activities.

PMID- 24582907
TI  - Using ictal high-frequency oscillations (80-500Hz) to localize seizure onset
      zones in childhood absence epilepsy: a MEG study.
AB  - This study aimed to use ictal high-frequency oscillations (HFOs) ranging from
      80Hz to 500Hz to locate seizure onset zones in childhood absence epilepsy (CAE)
      using non-invasive magnetoencephalography (MEG). Ten drug-naive children with CAE
      were studied using a 275-channel MEG system. MEG data were digitized at a
      sampling rate of 6000Hz. HFO spectral power in real-time spectrograms was
      assessed using Morlet continuous wavelet transform. Magnetic sources were
      volumetrically localized through dynamic magnetic source imaging with a slide
      window. HFOs were identified in all patients. The total time of fast ripples (250
      500Hz) was greater than that of ripples (80-250Hz) during absence seizures. The
      rate of fast ripples was associated with seizure frequency. HFO duration was
      significantly longer when co-occurring with spikes than when occurring
      independently, and the maximum frequency of HFOs co-occurring with spikes was
      higher than that of HFOs occurring independently. HFOs were predominantly
      localized in the medial prefrontal cortex (MPFC), whereas spikes were widespread
      to a variety of regions during the absence seizures. Compared with spikes, HFOs
      appeared to be more focal. The findings indicate that HFOs in the MPFC have a
      primary function in initializing epileptic activity in CAE. 

PMID- 24582908
TI  - A critical role for prefrontocortical endocannabinoid signaling in the regulation
      of stress and emotional behavior.
AB  - The prefrontal cortex (PFC) provides executive control of the brain in humans and
      rodents, coordinating cognitive, emotional, and behavioral responses to
      threatening stimuli and subsequent feedback inhibition of the hypothalamic
      pituitary-adrenal (HPA) axis. The endocannabinoid system has emerged as a
      fundamental regulator of HPA axis feedback inhibition and an important modulator
      of emotional behavior. However, the precise role of endocannabinoid signaling
      within the PFC with respect to stress coping and emotionality has only recently
      been investigated. This review discusses the current state of knowledge regarding
      the localization and function of the endocannabinoid system in the PFC, its
      sensitivity to stress and its role in modulating the neuroendocrine and
      behavioral responses to aversive stimuli. We propose a model whereby steady-state
      endocannabinoid signaling in the medial PFC indirectly regulates the outflow of
      pyramidal neurons by fine-tuning GABAergic inhibition. Local activation of this
      population of CB1 receptors increases the downstream targets of medial PFC
      activation, which include inhibitory interneurons in the basolateral amygdala,
      inhibitory relay neurons in the bed nucleus of the stria terminalis and monoamine
      cell bodies such as the dorsal raphe nucleus. This ultimately produces beneficial
      effects on emotionality (active coping responses to stress and reduced anxiety)
      and assists in constraining activation of the HPA axis. Under conditions of
      chronic stress, or in individuals suffering from mood disorders, this system may
      be uniquely recruited to help maintain appropriate function in the face of
      adversity, while breakdown of the endocannabinoid system in the medial PFC may
      be, in and of itself, sufficient to produce neuropsychiatric illness. Thus, we
      suggest that endocannabinoid signaling in the medial PFC may represent an
      attractive target for the treatment of stress-related disorders. 

PMID- 24582910
TI  - The misuse of benzodiazepines among adolescents: psychosocial risk factors in a
      national sample.
AB  - BACKGROUND: The misuse of benzodiazepines (BZs) among adolescents is an important
      issue within the fields of mental health, medicine, and public health. Though
      there is an increasing amount of research on prescription medication misuse, a
      relatively small number of studies focus on adolescent BZ misuse. The goal of
      this study, therefore, is to identify demographic and psychosocial factors that
      place adolescents at risk for misusing BZs. Additionally, the authors applied
      concepts from social bonding theory, social learning theory, and strain theory to
      determine the extent to which these concepts explain BZ misuse. METHODS: Using
      data from the 2011 National Survey of Drug Use & Health, multivariate logistic
      regression models were estimated to determine which factors were associated with
      an increased risk of BZ misuse. RESULTS: These findings help to describe the
      psychosocial profile of adolescent BZ misusers which should increase the ability
      of clinicians to identify patients who may be at greater risk for misuse.
      CONCLUSION: This study is particularly important within the context of
      psychiatry, where a clearer understanding of adolescent BZ misuse is critical for
      informing prevention efforts and developing best practices for prescribing BZs.

PMID- 24582909
TI  - Evaluation of sex differences in cannabinoid dependence.
AB  - BACKGROUND: Chronic recreational marijuana users often report withdrawal symptoms
      when trying to quit, with some reports suggesting withdrawal may be more
      pronounced in women. In animal models, female rodents show enhanced sensitivity
      to acute Delta(9)-tetrahydrocannabinol (THC) administration, but chronic
      administration has been studied little. METHODS: Sex differences in THC
      dependence in rats were examined. Adult male and female Sprague-Dawley rats were
      administered 30 mg/kg THC or vehicle twice daily for 6.5 days. On day 7, rats
      were challenged with vehicle or rimonabant, counterbalanced across dosing groups,
      and were assessed for withdrawal-related behaviors. RESULTS: During chronic THC
      dosing, disruption of estrous cycling and weight loss (both sexes) were observed.
      Whereas overt signs of withdrawal were minimal in THC-treated rats challenged
      with vehicle, rimonabant precipitated a pronounced withdrawal syndrome in THC
      dependent rats that was characterized by changes in a number of domains,
      including somatic (paw tremors, head twitches, and retropulsion), early-stage
      cognition (lack of locomotor habituation, disrupted prepulse inhibition), and
      affective (increased startle reactivity). With the exception of increased
      retropulsion in female rats, sex differences were not noted. In vehicle-treated
      rats, rimonabant induced puritis. CONCLUSIONS: This study represents the first
      examination of THC dependence in adult rats of both sexes, extends previous
      findings to females, and revealed some sex differences. The results suggest that
      the changes that occur during precipitated withdrawal from THC extend beyond
      somatic signs to more nuanced disruptions of cognitive and affective functioning.
      The breadth of withdrawal signs observed in rodents mirrors those that have been
      observed in humans.

PMID- 24582911
TI  - High-dose, weekly erlotinib is not an effective treatment in EGFR-mutated non
      small cell lung cancer-patients with acquired extracranial progressive disease on
      standard dose erlotinib.

PMID- 24582912
TI  - Serum 25-hydroxyvitamin D levels and survival in colorectal and breast cancer
      patients: systematic review and meta-analysis of prospective cohort studies.
AB  - AIM: To estimate the association between serum 25-hydroxyvitamin D (25(OH)D)
      levels and survival among colorectal and breast cancer patients. METHODS: We
      performed a comprehensive literature search of prospective cohort studies
      assessing the association of serum 25(OH)D levels with survival in colorectal and
      breast cancer patients. Study characteristics and results were extracted and dose
      response relationships were graphically displayed in a standardised manner. Meta
      analyses using random effects models were performed to estimate pooled hazard
      ratios. RESULTS: The systematic search yielded five studies including 2330
      colorectal cancer patients and five studies including 4413 breast cancer patients
      all of which compared mortality across two to five categories of 25(OH)D levels.
      Among colorectal cancer patients, pooled hazard ratios (95% confidence intervals)
      comparing highest with lowest categories were 0.71 (0.55-0.91) and 0.65 (0.49
      0.86) for overall and disease-specific mortality, respectively. For breast cancer
      patients, the corresponding pooled estimates were 0.62 (0.49-0.78) and 0.58 (0.38
      0.84), respectively. No significant evidence of heterogeneity between studies was
      observed. CONCLUSION: Higher 25(OH)D levels (>75nmol/L) were associated with
      significantly reduced mortality in patients with colorectal and breast cancer.
      Randomised controlled trials are needed to evaluate whether vitamin D
      supplementation can improve survival in colorectal and breast cancer patients
      with low vitamin D status (25(OH)D<50nmol/L) at diagnosis and before treatment.

PMID- 24582913
TI  - Survival from childhood acute lymphoblastic leukaemia in West Germany: does socio
      demographic background matter?
AB  - BACKGROUND: Sex, age, immunophenotype and white blood cell count at diagnosis are
      well accepted predictors of survival from acute lymphoblastic leukaemia (ALL) in
      children. Less is known about the relationship between socio-economic
      determinants and survival from paediatric ALL, studied here for the first time in
      German children. METHODS: ALL cases were diagnosed between 1992 and 1994 and
      their parents interviewed during a previous nationwide case-control study.
      Children were followed-up for 10 years after diagnosis by the German Childhood
      Cancer Registry. Cox proportional hazards models estimating hazard ratios (HRs)
      were calculated to assess the impact of selected socio-demographic
      characteristics on overall and event-free survival. RESULTS: Overall survival was
      82.5%, with a higher proportion of girls than boys surviving (85% versus 81%). We
      found a non-linear relationship between age at diagnosis and survival, with
      poorer survival in infants and children aged >5 years. There was no association
      between socio-economic factors and survival or risk of relapse. For five levels
      of increasing family income, all HRs were close to one. No relationship was seen
      with parental educational level. CONCLUSION: Socio-economic determinants did not
      affect ALL survival in West German children, in contrast to studies from some
      other countries. Dissimilarities in social welfare systems, including access to
      health care, lifestyle and differences in treatment may contribute to these
      differences in findings. Our observation of no social inequalities in paediatric
      ALL survival is reassuring, but needs continued monitoring to assess the
      potential impact of evolvement of treatment options and changes in paediatric
      health service.

PMID- 24582914
TI  - RAS mutations and cetuximab in locally advanced rectal cancer: results of the
      EXPERT-C trial.
AB  - BACKGROUND: RAS mutations predict resistance to anti-epidermal growthfactor
      receptor (EGFR) monoclonal antibodies in metastatic colorectal cancer. We
      analysed RAS mutations in 30 non-metastatic rectal cancer patients treated with
      or without cetuximab within the 31 EXPERT-C trial. METHODS: Ninety of 149
      patients with tumours available for analysis were KRAS/BRAF wild-type, and
      randomly assigned to capecitabine plus oxaliplatin (CAPOX) followed by
      chemoradiotherapy, surgery and adjuvant CAPOX or the same regimen plus cetuximab
      (CAPOX-C). Of these, four had a mutation of NRAS exon 3, and 84 were
      retrospectively analysed for additional KRAS (exon 4) and NRAS (exons 2/4)
      mutations by using bi-directional Sanger sequencing. The effect of cetuximab on
      study end-points in the RAS wild-type population was analysed. RESULTS: Eleven
      (13%) of 84 patients initially classified as KRAS/BRAF wild-type were found to
      have a mutation in KRAS exon 4 (11%) or NRAS exons 2/4 (2%). Overall, 78/149
      (52%) assessable patients were RAS wild-type (CAPOX, n=40; CAPOX-C, n=38). In
      this population, after a median follow-up of 63.8months, in line with the initial
      analysis, the addition of cetuximab was associated with numerically higher, but
      not statistically significant, rates of complete response (15.8% versus 7.5%,
      p=0.31), 5-year progression-free survival (75.5% versus 67.5%, hazard ratio (HR)
      0.61, p=0.25) and 5-year overall survival (83.8% versus 70%, HR 0.54, p=0.20).
      CONCLUSIONS: RAS mutations beyond KRAS exon 2 and 3 were identified in 17% of
      locally advanced rectal cancer patients. Given the small sample size, no
      definitive conclusions on the effect of additional RAS mutations on cetuximab
      treatment in this setting can be drawn and further investigation of RAS in larger
      studies is warranted.

PMID- 24582915
TI  - Effect of integrating 3D-mammography (digital breast tomosynthesis) with 2D
      mammography on radiologists' true-positive and false-positive detection in a
      population breast screening trial.
AB  - OBJECTIVE: We investigated the effect of integrating three-dimensional (3D)
      mammography with 2D-mammography on radiologists' detection measures in the
      'screening with tomosynthesis or standard mammography' (STORM) trial. METHODS:
      STORM, a prospective population-based trial (Trento and Verona breast screening
      services) compared sequential screen-reading: 2D-mammography alone and integrated
      2D/3D-mammography. Radiologist-specific detection measures were calculated for
      each screen-reading phase for eight radiologists: number of detected cancers,
      proportion of true-positive (TP) detection, and number and rate of false-positive
      (FP) recalls (FPR). We estimated the incremental cancer detection rate (CDR).
      RESULTS: There were 59 cancers and 395 false recalls amongst 7292 screening
      participants. At 2D-mammography screening, radiologist-specific TP detection
      ranged between 38% and 83% (median 63%; mean 60% and sd 15.4%); at integrated
      2D/3D-mammography, TP detection ranged between 78% and 93% (median 87%; mean 87%
      and sd 5.2%). For all but one radiologist, 2D/3D-mammography improved breast
      cancer detection (relative to 2D-mammography) ranging between 0% and 54% (median
      29%; mean 27% and sd 16.2%) increase in the proportion of detected cancers.
      Incremental CDR attributable to integrating 3D-mammography in screening varied
      between 0/1000 and 5.3/1000 screens (median 1.8/1000; mean 2.3/1000 and sd
      1.6/1000). Radiologist-specific FPR for 2D-mammography ranged between 1.5% and
      4.2% (median 3.1%; mean 2.9% and sd 0.87%), and FPR based on the integrated 2D/3D
      mammography read ranged between 1.0% and 3.3% (median 2.4%; mean 2.2% and sd
      0.72%). Integrated 2D/3D-mammography screening, relative to 2D-mammography, had
      the effect of reducing FP and increasing TP detection for most radiologists.
      CONCLUSION: There was broad variability in radiologist-specific TP detection at
      2D-mammography and hence in the additional TP detection and incremental CDR
      attributable to integrated 2D/3D-mammography; more consistent (less variable) TP
      detection estimates were observed for the integrated screen-read. Integrating 3D
      mammography with 2D-mammography improves radiologists' screen-reading through
      improved cancer detection and/or reduced FPR, with most readers achieving both
      using integrated 2D/3D mammography.

PMID- 24582916
TI  - Characterization of eating patterns among individuals with eating disorders: what
      is the state of the plate?
AB  - Eating disorders will affect approximately 18 million individuals in the United
      States at some point in their lives, and are associated with significant
      psychological distress, psychosocial and quality-of-life impairment, medical
      morbidity, and mortality. Although aberrant eating behaviors play a central role
      in diagnostic definitions for eating disorders, much remains to be learned about
      eating patterns, diet quality, and energy balance among individuals with eating
      pathology. The goal of the current paper was to systematically review and
      integrate findings from published research studies characterizing the eating
      behaviors of individuals with eating disorders, including findings from both
      descriptive and laboratory-based research. We also describe results from studies
      using ecological momentary assessment - a methodology that assesses individuals'
      behaviors in their natural environment as they occur, which may reduce
      retrospective recall bias, and provide improved ability to prospectively assess
      the temporal occur of changes in multiple eating behaviors over time. We conclude
      with suggestions for future research, including the need for additional studies
      to test for differences in eating patterns among different demographic groups of
      individuals with eating disorders, and the need for new, more objective,
      assessment tools. 

PMID- 24582917
TI  - Brain-derived neurotrophic factor in the amygdala mediates susceptibility to fear
      conditioning.
AB  - Fear conditioning in animals has been used extensively to model clinical anxiety
      disorders. While individual animals exhibit marked differences in their
      propensity to undergo fear conditioning, the physiologically relevant mediators
      have not yet been fully characterized. Here, we demonstrate that C57BL/6 inbred
      mouse strain subjected to a regimen of chronic social defeat stress (CSDS) can be
      separated into susceptible and resistant subpopulations that display different
      levels of fear responses in an auditory fear conditioning paradigm. Susceptible
      mice had significantly more c-Fos protein expression in neurons of the
      basolateral amygdala (BLA) following CSDS and showed exaggerated conditioned fear
      responses, while there were no significant differences between groups in innate
      anxiety- and depressive-like behaviors. Through the use of conditional brain
      derived neurotrophic factor (BDNF) knockout strategies, we find that elevated BLA
      BDNF level following fear conditioning training is a key mediator contributing to
      determine the levels of conditioned fear responses. Our results also show that
      relative to susceptible mice, resistant mice had a much faster recovery from
      conditioned stimuli-induced cardiovascular and corticosterone responses. Systemic
      administration of norepinephrine reuptake inhibitor atomoxetine increased c-Fos
      protein expression in BLA neurons following fear conditioning training and
      promoted the expression of conditioned fear in resistant mice. Conversely,
      administration of beta-adrenergic receptor antagonist propranolol reduced fear
      conditioning training-induced c-Fos protein expression in BLA neurons and reduced
      conditioned fear responses in susceptible mice. These findings reveal a novel
      role for the BDNF signaling within the BLA in mediating individual differences in
      autonomic, neuroendocrine and behavioral reactivity to fear conditioning. 

PMID- 24582918
TI  - Electrophysiological indices of interference resolution covary with individual
      fluid intelligence: investigating reactive control processes in a 3-back working
      memory task.
AB  - It has been proposed that the well-established relationship between working
      memory (WM) and fluid intelligence (gf) is mediated by executive mechanisms
      underlying interference control. The latter relies upon the integrity of a
      frontoparietal brain network, whose activity is modulated by general cognition.
      In regards to the chronology of this activation, only few EEG studies
      investigated the topic, although none of them examined the regional interaction
      or the effects of individual differences in gf. The current investigation sought
      at extending previous research by characterizing the EEG markers (temporal
      activation and regional coupling) of interference control and the effects of the
      individual variation in gf. To this end, we recorded the EEG activity of 33
      participants while performing verbal and spatial versions of a 3-back WM task. In
      a separate session, participants were administered with a test of fluid
      intelligence. Interference-inducing trials were associated with an increased
      negativity in the frontal scalp region occurring in two separate time windows and
      probably reflecting two different stages of the underlying cognitive process. In
      addition, we found that scalp distribution of such activity differed among
      individuals, being the strongest activation of the left and right frontolateral
      sites related to high gf level. Finally, high- and low-gf participants showed
      different patterns in the modulation of regional connectivity (electrodes
      coherence in the range of 4.5-7.5Hz) according to changes in attention load among
      types of trials. Our findings suggest that high-gf participants may rely upon
      effective engagement and modulation of attention resources to face interference.

PMID- 24582919
TI  - Bayesian model selection of template forward models for EEG source
      reconstruction.
AB  - Several EEG source reconstruction techniques have been proposed to identify the
      generating neuronal sources of electrical activity measured on the scalp. The
      solution of these techniques depends directly on the accuracy of the forward
      model that is inverted. Recently, a parametric empirical Bayesian (PEB) framework
      for distributed source reconstruction in EEG/MEG was introduced and implemented
      in the Statistical Parametric Mapping (SPM) software. The framework allows us to
      compare different forward modeling approaches, using real data, instead of using
      more traditional simulated data from an assumed true forward model. In the
      absence of a subject specific MR image, a 3-layered boundary element method (BEM)
      template head model is currently used including a scalp, skull and brain
      compartment. In this study, we introduced volumetric template head models based
      on the finite difference method (FDM). We constructed a FDM head model equivalent
      to the BEM model and an extended FDM model including CSF. These models were
      compared within the context of three different types of source priors related to
      the type of inversion used in the PEB framework: independent and identically
      distributed (IID) sources, equivalent to classical minimum norm approaches,
      coherence (COH) priors similar to methods such as LORETA, and multiple sparse
      priors (MSP). The resulting models were compared based on ERP data of 20 subjects
      using Bayesian model selection for group studies. The reconstructed activity was
      also compared with the findings of previous studies using functional magnetic
      resonance imaging. We found very strong evidence in favor of the extended FDM
      head model with CSF and assuming MSP. These results suggest that the use of
      realistic volumetric forward models can improve PEB EEG source reconstruction.

PMID- 24582920
TI  - Increased sensitivity of fast BOLD fMRI with a subject-specific hemodynamic
      response function and application to epilepsy.
AB  - Activation detection in functional Magnetic Resonance Imaging (fMRI) typically
      assumes the hemodynamic response to neuronal activity to be invariant across
      brain regions and subjects. Reports of substantial variability of the morphology
      of blood-oxygenation-level-dependent (BOLD) responses are accumulating,
      suggesting that the use of a single generic model of the expected response in
      general linear model (GLM) analyses does not provide optimal sensitivity due to
      model misspecification. Relaxing assumptions of the model can limit the impact of
      hemodynamic response function (HRF) variability, but at a cost on model
      parsimony. Alternatively, better specification of the model could be obtained
      from a priori knowledge of the HRF of a given subject, but the effectiveness of
      this approach has only been tested on simulation data. Using fast BOLD fMRI, we
      characterized the variability of hemodynamic responses to a simple event-related
      auditory-motor task, as well as its effect on activation detection with GLM
      analyses. We show the variability to be higher between subjects than between
      regions and variation in different regions to correlate from one subject to the
      other. Accounting for subject-related variability by deriving subject-specific
      models from responses to the task in some regions lead to more sensitive
      detection of responses in other regions. We applied the approach to epilepsy
      patients, where task-derived patient-specific models provided additional
      information compared to the use of a generic model for the detection of BOLD
      responses to epileptiform activity identified on scalp electro-encephalogram
      (EEG). This work highlights the importance of improving the accuracy of the model
      for detecting neuronal activation with fMRI, and the fact that it can be done at
      no cost to model parsimony through the acquisition of independent a priori
      information about the hemodynamic response.

PMID- 24582921
TI  - Neural correlates of visual crowding.
AB  - In visual crowding, target discrimination strongly deteriorates when flanking
      elements are added. We have recently shown that crowding cannot be explained by
      simple low-level interactions and that grouping is a key component instead. We
      presented a vernier flanked by arrays of vertical lines. When the flankers had
      the same lengths as the vernier, offset discrimination was strongly impaired.
      When longer flankers were presented, crowding was weaker. We proposed that
      crowding is strong when the flankers group with the target (equal length
      flankers). When the target segregates from the flankers, crowding is weaker (long
      flankers). To understand the neurophysiological mechanisms of grouping in
      crowding, here, we adapted the above vernier paradigm to a high-density EEG
      study. The P1 component reflected basic stimulus characteristics (flanker length)
      but not crowding. Crowding emerged slowly and manifested as a suppression of the
      N1 component (after 180ms). Using inverse solutions, we found that the N1
      suppression was caused by reduced neural activity in high-level visual areas such
      as the lateral occipital cortex. Our results suggest that crowding occurs when
      elements are grouped into wholes, a process reflected by the N1 component.

PMID- 24582922
TI  - Chocolate intake and diabetes risk.
AB  - BACKGROUND & AIMS: In-vitro and rodent studies, and short-term human trials
      suggest that compounds in chocolate can enhance insulin sensitivity. Also, a
      recent prospective Japanese epidemiological analysis found that long-term
      chocolate consumption was inversely associated with diabetes risk. The objective
      of the present analysis was to test the epidemiological association between long
      term chocolate consumption and diabetes risk in a U.S. cohort. METHODS:
      Multivariable prospective Cox Regression analysis with time-dependent covariates
      was used to examine data from 7802 participants in the prospective
      Atherosclerosis Risk in Communities Cohort. The data included 861 new diabetes
      cases during 98,543 person-years of follow up (mean = 13.3 years). RESULTS:
      Compared to participants who ate 1 oz of chocolate less often than monthly, those
      who ate it 1-4 times/month, 2-6 times/week and >= 1 time/day had relative risks
      of being diagnosed with diabetes that were lower by 13% (95% confidence interval:
      -2%, 25%), 34% (18%, 47%) and 18% (-10%, 38%). These relative risks applied to
      participants without evidence of preexisting serious chronic disease that
      included diabetes, heart attacks, stroke or cancer. In conclusion, the risk of
      diabetes decreased as the frequency of chocolate intake increased, up to 2-6
      servings (1 oz) per week. Consuming >= 1 serving per day did not yield
      significantly lower relative risk. CONCLUSIONS: These results suggest that
      consuming moderate amount of chocolate may reduce the risk of diabetes. Further
      research is required to confirm and explore these findings.

PMID- 24582923
TI  - Glutamine in critically ill patients: trial-sequential analysis.

PMID- 24582924
TI  - Tree testing of hierarchical menu structures for health applications.
AB  - To address the need for greater evidence-based evaluation of Health Information
      Technology (HIT) systems we introduce a method of usability testing termed tree
      testing. In a tree test, participants are presented with an abstract hierarchical
      tree of the system taxonomy and asked to navigate through the tree in completing
      representative tasks. We apply tree testing to a commercially available health
      application, demonstrating a use case and providing a comparison with more
      traditional in-person usability testing methods. Online tree tests (N=54) and in
      person usability tests (N=15) were conducted from August to September 2013. Tree
      testing provided a method to quantitatively evaluate the information structure of
      a system using various navigational metrics including completion time, task
      accuracy, and path length. The results of the analyses compared favorably to the
      results seen from the traditional usability test. Tree testing provides a
      flexible, evidence-based approach for researchers to evaluate the information
      structure of HITs. In addition, remote tree testing provides a quick, flexible,
      and high volume method of acquiring feedback in a structured format that allows
      for quantitative comparisons. With the diverse nature and often large quantities
      of health information available, addressing issues of terminology and concept
      classifications during the early development process of a health information
      system will improve navigation through the system and save future resources. Tree
      testing is a usability method that can be used to quickly and easily assess
      information hierarchy of health information systems. 

PMID- 24582925
TI  - Sample size estimation in diagnostic test studies of biomedical informatics.
AB  - OBJECTIVES: This review provided a conceptual framework of sample size
      calculations in the studies of diagnostic test accuracy in various conditions and
      test outcomes. METHODS: The formulae of sample size calculations for estimation
      of adequate sensitivity/specificity, likelihood ratio and AUC as an overall index
      of accuracy and also for testing in single modality and comparing two diagnostic
      tasks have been presented for desired confidence interval. RESULTS: The required
      sample sizes were calculated and tabulated with different levels of accuracies
      and marginal errors with 95% confidence level for estimating and for various
      effect sizes with 80% power for purpose of testing as well. The results show how
      sample size is varied with accuracy index and effect size of interest.
      CONCLUSION: This would help the clinicians when designing diagnostic test studies
      that an adequate sample size is chosen based on statistical principles in order
      to guarantee the reliability of study.

PMID- 24582926
TI  - Human hepatocytes with drug metabolic function induced from fibroblasts by
      lineage reprogramming.
AB  - Obtaining fully functional cell types is a major challenge for drug discovery and
      regenerative medicine. Currently, a fundamental solution to this key problem is
      still lacking. Here, we show that functional human induced hepatocytes (hiHeps)
      can be generated from fibroblasts by overexpressing the hepatic fate conversion
      factors HNF1A, HNF4A, and HNF6 along with the maturation factors ATF5, PROX1, and
      CEBPA. hiHeps express a spectrum of phase I and II drug-metabolizing enzymes and
      phase III drug transporters. Importantly, the metabolic activities of CYP3A4,
      CYP1A2, CYP2B6, CYP2C9, and CYP2C19 are comparable between hiHeps and freshly
      isolated primary human hepatocytes. Transplanted hiHeps repopulate up to 30% of
      the livers of Tet-uPA/Rag2(-/-)/gammac(-/-) mice and secrete more than 300 MUg/ml
      human ALBUMIN in vivo. Our data demonstrate that human hepatocytes with drug
      metabolic function can be generated by lineage reprogramming, thus providing a
      cell resource for pharmaceutical applications. 

PMID- 24582927
TI  - Direct reprogramming of human fibroblasts to functional and expandable
      hepatocytes.
AB  - The generation of large numbers of functional human hepatocytes for cell-based
      approaches to liver disease is an important and unmet goal. Direct reprogramming
      of fibroblasts to hepatic lineages could offer a solution to this problem but so
      far has only been achieved with mouse cells. Here, we generated human induced
      hepatocytes (hiHeps) from fibroblasts by lentiviral expression of FOXA3, HNF1A,
      and HNF4A. hiHeps express hepatic gene programs, can be expanded in vitro, and
      display functions characteristic of mature hepatocytes, including cytochrome P450
      enzyme activity and biliary drug clearance. Upon transplantation into mice with
      concanavalin-A-induced acute liver failure and fatal metabolic liver disease due
      to fumarylacetoacetate dehydrolase (Fah) deficiency, hiHeps restore the liver
      function and prolong survival. Collectively, our results demonstrate successful
      lineage conversion of nonhepatic human cells into mature hepatocytes with
      potential for biomedical and pharmaceutical applications. 

PMID- 24582929
TI  - Observing of chain-schedule stimuli.
AB  - A classical-conditioning account of the processes maintaining behavior under
      chained schedules entails a backward transmission of conditioned-reinforcement
      effects. Assessing this process in traditional chain schedules is limited because
      the response maintained by stimulus onset accompanied by each link in a chain
      schedule may also be maintained by the primary reinforcer. In the present
      experiment, an observing response was used to measure the conditioned-reinforcing
      effects of stimuli associated with a three-link chain variable-time (VT) food
      schedule, and resistance-to-change tests (extinction and prefeeding) were
      implemented to examine if a backward transmission of reinforcement effects occur.
      Four pigeons served as subjects. Observing was maintained by the production of
      stimuli correlated with links of a three-link chain VT schedule with the middle
      link stimulus maintaining the highest rate of observing, followed by the initial
      link stimulus and the terminal-link stimulus maintaining the lowest observing
      rate. Results from resistance-to-change tests of extinction and prefeeding were
      not supportive of a backward transmission of reinforcement effects and in
      general, the pattern of resistance-to-change was forward. Based on past and
      current research, it appears that a backward pattern of relative rate decreases
      in responses maintained by stimuli correlated with a chain schedule due to
      disruption (i.e., extinction and prefeeding) is not a ubiquitous process that is
      evident within different chain-schedule arrangements. 

PMID- 24582928
TI  - Pioglitazone, a PPARgamma agonist, provides comparable protection to angiotensin
      converting enzyme inhibitor ramipril against adriamycin nephropathy in rat.
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma) agonists have been
      shown to ameliorate diabetic nephropathy, but much less are known about their
      effects in non-diabetic nephropathies. In the present study, metabolic
      parameters, blood pressure, aortic endothelial function along with molecular and
      structural markers of glomerular and tubulointerstitial renal damage, were
      studied in a rat model of normotensive nephropathy induced by adriamycin and
      treated with PPARgamma agonist pioglitazone (12mg/kg, po), angiotensin converting
      enzyme (ACE) inhibitor ramipril (1mg/kg, po) or their combination. Pioglitazone
      had no effect on systolic blood pressure, marginally reduced glycemia and
      improved aortic endothelium-dependent relaxation. In the kidney, pioglitazone
      prevented the development of proteinuria and focal glomerulosclerosis to the
      similar extent as blood-pressure lowering ramipril. Renoprotection provided by
      either treatment was associated with a reduction in the cortical expression of
      profibrotic plasminogen activator inhibitor-1 and microvascular damage-inducing
      endothelin-1, and a limitation of interstitial macrophage influx. Treatment with
      PPARgamma agonist, as well as ACE inhibitor comparably affected renal expression
      of the renin-angiotensin system (RAS) components, normalizing increased renal
      expression of ACE and enhancing the expression of Mas receptor. Interestingly,
      combined pioglitazone and ramipril treatment did not provide any additional
      renoprotection. These results demonstrate that in a nondiabetic renal disease,
      such as adriamycin-induced nephropathy, PPARgamma agonist pioglitazone provides
      renoprotection to a similar extent as an ACE inhibitor by interfering with the
      expression of local RAS components and attenuating related profibrotic and
      inflammatory mechanisms. The combination of the both agents, however, does not
      lead to any additional renal benefit. 

PMID- 24582930
TI  - High urine IP-10 levels associate with chronic HCV infection.
AB  - OBJECTIVES: Independent of IL-28B polymorphisms, blood IP-10 is a promising
      biomarker for predicting therapy response in chronic HCV infection. Urine IP-10
      has been proposed as a biomarker in tuberculosis, but to date, no urine
      biomarkers for HCV infection have been evaluated. In this cross-sectional study,
      we assessed whether IP-10 is detectable in the urine of chronically HCV-infected
      patients, and if so, whether urine IP-10 correlates with serum IP-10 and HCV
      specific clinical parameters. METHODS: IP-10 was measured by ELISA in serum and
      urine concomitantly taken from 38 HCV-viremic patients, 10 cured-HCV subjects and
      11 healthy donors enrolled as controls. RESULTS: The urine of HCV-viremic
      patients showed measurable amounts of IP-10, although significantly lower than in
      serum (p < 0.0001). Urine IP-10 was normalized with creatinuria levels and we
      found that the urine IP-10/creatinuria ratio was significantly higher in HCV
      viremic patients than in cured-HCV subjects (p = 0.002) and healthy donors (p =
      0.008), and that it significantly correlated with transaminases (p = 0.01),
      although the correlation was low. Similarly, the serum IP-10 level significantly
      associated with HCV-viremic patients (p < 0.0001) and correlated with
      transaminases (p < 0.0001). CONCLUSIONS: For the first time to our knowledge, we
      show that IP-10 is detected and increased in the urine of HCV-viremic patients
      compared to healthy donors and cured-HCV subjects.

PMID- 24582931
TI  - The association between obstetrical interventions and late preterm birth.
AB  - OBJECTIVE: There is concern that obstetric interventions (prelabor cesarean
      section and induced delivery) are drivers of late preterm (LP) birth. Our
      objective was to evaluate the independent association between obstetric
      interventions and LP birth and explore associated independent maternal and fetal
      risk factors for LP birth. STUDY DESIGN: In this population-based cross-sectional
      study, the BORN Information System was used to identify all infants born between
      34 and 40 completed weeks of gestation between 2005 and 2012 in Ontario, Canada.
      The association between obstetric interventions (preterm cesarean section and
      induced delivery) and LP birth (34 to 36 completed weeks' gestation vs 37 to 40
      completed weeks' gestation) was assessed using generalized estimating equation
      regression. RESULTS: Of 917,013 births between 34 and 40 weeks, 49,157 were LP
      (5.4%). In the adjusted analysis, "any obstetric intervention" (risk ratio [RR],
      0.65; 95% confidence interval [CI], 0.57-0.74), induction (RR, 0.71; 95% CI, 0.61
      0.82) and prelabor cesarean section (RR, 0.66; 95% CI, 0.59-0.74) were all
      associated with a lower likelihood of LP vs term birth. Several independent
      potentially modifiable risk factors for LP birth were identified including
      previous cesarean section (RR, 1.28; 95% CI, 1.16-1.40), smoking during pregnancy
      (RR, 1.28; 95% CI, 1.21-1.36) and high material (RR, 1.1; 95% CI, 1.03-1.18) and
      social (RR, 1.09; 95% CI, 1.02-1.16) deprivation indices. CONCLUSION: After
      accounting for differences in maternal and fetal risk, LP births had a 35% lower
      likelihood of obstetric interventions than term births. Obstetric care providers
      may be preferentially avoiding induction and prelabor cesarean section between 34
      and 37 weeks' gestation.

PMID- 24582932
TI  - Complexes of polyglutamic acid and long-chain alkanoylcholines: nanoparticle
      formation and drug release.
AB  - Ionic complexes of microbial poly(gamma-glutamic acid) and alkanoylcholines are
      fully bio-based comb-like systems able to self-organize in an ordered amphiphilic
      structure made of hydrophobic and hydrophilic alternating layers. Incubation of
      complex films under physiological conditions for one month promoted dissociation
      of the complex and hydrolysis of the choline ester without almost degradation of
      polyglutamic acid. Complex decomposition rates were depending on alkanoyl chain
      length and on complex stoichiometry as well. Nanoparticles with 50-100 nm
      diameter were successfully prepared from the stearoylcholine complex with a
      surfactant to polymer ratio of 0.75 and loaded with theophylline, carbamazepine
      or doxorubicin drugs. The releasing of the drugs from nanoparticles took place
      upon incubation at very different rates depending on the drug. Theophylline and
      carbamazepine were discharged in hours whereas doxorubicin was very slowly
      delivered along months. The observed differences were related to the different
      interaction mechanism operating between the drug and the complex.

PMID- 24582933
TI  - Fucans from a Tunisian brown seaweed Cystoseira barbata: structural
      characteristics and antioxidant activity.
AB  - Sulfated polysaccharides from brown seaweeds are known to be a topic of numerous
      studies, due to their beneficial biological properties including antioxidant
      activity. Fucans were isolated from the brown seaweed Cystoseira barbata
      harvested in Tunisia. ATR-FTIR and (1)H-NMR spectroscopies demonstrated that C.
      barbata sulfated polysaccharides (CBSPs) consisted mainly of 3-linked-alpha-l
      fucopyranosyl backbone, acetylated and mostly sulfated at C-4. Molar degrees of
      sulfation and acetylation of CBSPs were 0.79 and 0.27, respectively. Neutral
      sugars analysis determined by gas chromatography-mass spectrometry (GC-MS) showed
      that CBSPs were mainly composed of fucose (44.6%) and galactose (34.32%) with few
      amounts of other sugars such as glucose (7.55%), rhamnose (6.41%), xylose (4.21%)
      and mannose (2.91%). CBSPs were examined for in vitro antioxidant properties
      using various antioxidant assays. CBSPs exhibited important DPPH radical
      scavenging activity (100% inhibition at a concentration of 1.5mg/ml) and
      considerable ferric reducing potential (24.62 mg ascorbic acid equivalents).
      Effective chelating activity and significant protection activity against hydroxyl
      radical induced DNA breakage were also recorded for CBSPs. However, in the
      linoleate-beta-carotene system, CBSPs exerted moderate antioxidant activity (62%
      inhibition at a concentration of 1.5mg/ml). Therefore, CBSPs can be used as a
      potent natural antioxidant in food industry or in the pharmaceutical field.

PMID- 24582934
TI  - Statistical optimization of pullulan production from Asian palm kernel and
      evaluation of its properties.
AB  - Pullulan, a biodegradable exopolysaccharide, was produced from Asian Palmyra palm
      kernel by solid-state fermentation. Levels of medium variables, namely carbon to
      nitrogen ratio (C/N), pH, NaCl concentration and ZnSO4.5H2O concentration were
      optimized to maximize pullulan production using Box-Behnken design of
      experiments. Optimal values were predicted as: C/N ratio - 28.1, pH - 6.6, NaCl -
      0.78 g/l and ZnSO4.5H2O - 0.37 g/l. Theoretical pullulan yield predicted under
      optimum condition was 30.4 mg/gds. Pullulan was produced under optimum condition
      and an experimental yield of 28.7 +/- 0.3mg/gds was obtained. (13)C NMR spectra
      of the exopolysaccharide produced from Asian palm kernel revealed the presence of
      anomeric alpha (1->6) linked maltosyl units. The weight-average molecular weight
      of the polymer was determined to be 8.4*10(6)Da by gel permeation chromatography.
      Thermal decomposition temperature of pullulan was obtained to be 245 degrees C.
      The tensile strength of pullulan film (0.5mm thick) was found to be 27 MPa.

PMID- 24582935
TI  - Antibacterial, mechanical, and barrier properties of sago starch film
      incorporated with Betel leaves extract.
AB  - The antimicrobial, mechanical and barrier properties and light transmission of
      sago starch film incorporated with different percentage of Betel leaf extract
      (5%, 10%, 20%, and 30%) were evaluated. With regard to mechanical properties,
      tensile strength decreased when the percentage of extract increased. Elongation
      at break (%) and seal strength (N/m) increased with increasing percentage of
      extract from 5% to 20%, while decreased for films containing 30% extract due to
      heterogeneity of films in this percentage. With regard to barrier properties,
      water vapour and oxygen barrier properties decreased in all samples when
      percentage of the extract increased. Antimicrobial activity of all the films
      increased against both Gram positive and Gram negative bacteria as percentage of
      Betel leaf extract increased, except for Psuedomonas aeruginosa, which was not
      susceptible at any percentage of the extract. 

PMID- 24582936
TI  - Preparation of carboxymethyl cellulose sulfates and its application as
      anticoagulant and wound dressing.
AB  - Tissue engineering is aiming to build an artificial environment or biological
      scaffold material that imitates the living environment of cells in the body. In
      this work, carboxymethyl cellulose sulfates were prepared by reacting
      carboxymethyl cellulose with N(SO3Na)3 which was synthesized by sodium bisulfite
      and sodium nitrite in aqueous solution. The reaction conditions affected the
      degree of substitution (DS) were measured by the barium sulfate nephelometry
      method. And the anticoagulant activity of carboxymethyl cellulose sulfates with
      different DS, concentration and molecular weights were investigated by the
      activated partial thromboplastin time (APTT), thrombin time (TT) and prothrombin
      time (PT). In addition, the effect of carboxymethyl cellulose sulfates on wound
      healing had been evaluated by the rate of wound healing and the histological
      examinations. The results indicated that the introduction of sulfate groups into
      the carboxymethyl cellulose sulfates improved its anticoagulant activity, and the
      wound dressings treated with carboxymethyl cellulose sulfates obviously promoted
      wound healing. 

PMID- 24582937
TI  - Optimal fabrication of nanofiber membranes from ionized-bicomponent
      cellulose/polyethyleneoxide solutions.
AB  - The effect of cellulose acetate (CA)/polyethyleneoxide (PEO) ratio (0.5-1.5 wt%)
      and lithium chloride (LiCl) content (0.25-0.75%, w/v) on the viscosity, surface
      tension and electrical conductivity (EC) of the solutions and diameter of the
      fabricated nanofiber membranes (NFMs) were optimized using response surface
      methodology-central composite rotatable design (RSM-CCRD). The NFMs were composed
      of non-woven fibers with maximum diameter of 121.70 +/- 33.40. Second-order
      polynomial models with high R(2) values (0.977-0.998) were developed using
      multiple linear regression analysis. Results showed that the NFMs diameter and
      morphology were significantly affected by CA and LiCl contents (p<0.0001). The
      overall optimum region was found to be at the combined level of CA to PEO ratio
      of 1.5 wt% and LiCl content of 0.5% (w/v). At the optimum point, the viscosity,
      surface tension, EC and diameter were 0.425 +/- 0.036 Pas, 36.21 +/- 1.25 mN/m,
      0.383 +/- 0.014 ms/cm, and 82.19 +/- 3.01 nm, respectively. The most uniform and
      bead-free NFMs were fabricated from the solution formulated with 1 wt% CA/PEO and
      0.85% (w/v) of LiCl content.

PMID- 24582938
TI  - The D14 and R138 ion pair is involved in dimeric arginine kinase activity,
      structural stability and folding.
AB  - Arginine kinase (AK) is a key enzyme in cellular energy metabolism of
      invertebrates. There are two conserved amino acid residues D14 and R138 in
      dimeric AK which form inter-subunit hydrogen bond. In Stichopus japonicus AK,
      mutations in these residues caused pronounced loss of activity, conformational
      changes and distinct substrate synergism alteration. Mutations (R138G, R138A and
      D14G) abolished D14 and R138 interaction disrupted the structure or conformation
      of S. japonicus AK. These R138G, R138A and D14G mutations changed their native
      assembles of dimeric AK and caused them in a partially unfolded state. The
      partially unfolded state of these mutant AKs made them prone to aggregate under
      environmental stress. The D14E/R138K and R138K mutant AKs showed similar
      characteristics to those of WT AK for forming the interaction which could
      replacement roles of D14 and R138 interaction. These results suggested that D14
      and R138 interaction is involved in AK's activity, substrate synergism and
      structural stability.

PMID- 24582940
TI  - Networking.

PMID- 24582939
TI  - GATA-4 induces changes in electrophysiological properties of rat mesenchymal stem
      cells.
AB  - BACKGROUND: Transplanted mesenchymal stem cells (MSC) can differentiate into
      cardiac cells that have the potential to contribute to heart repair following
      ischemic injury. Overexpression of GATA-4 can significantly increase
      differentiation of MSC into cardiomyocytes (CM). However, the specific impact of
      GATA-4 overexpression on the electrophysiological properties of MSC-derived CM
      has not been well documented. METHODS: Adult rat bone marrow MSC were
      retrovirally transduced with GATA-4 (MSC(GATA-4)) and GFP (MSC(Null)) and
      subsequently co-cultured with neonatal rat ventricular cardiomyocytes (CM).
      Electrophysiological properties and mRNA levels of ion channels were assessed in
      MSC using patch-clamp technology and real-time PCR. RESULTS: MSC(GATA-4)
      exhibited higher levels of the TTX-sensitive Na(+) current (INa.TTX), L-type
      calcium current (ICa.L), transient outward K(+) current (Ito), delayed rectifier
      K(+) current (IKDR) and inwardly rectifying K(+) current (IK1) channel activities
      reflective of electrophysiological characteristics of CM. Real-time PCR analyses
      showed that MSC(GATA-4) exhibited upregulated mRNA levels of Kv1.2, Kv2.1,
      SCN2a1, CCHL2a, KV1.4 and Kir1.1 channels versus MSC(Null). Interestingly,
      MSC(GATA-4) treated with IGF-1 neutralizing antibodies resulted in a significant
      decrease in Kir1.1, Kv2.1, KV1.4, CCHL2a and SCN2a1 channel mRNA expression.
      Similarly, MSC(GATA-4) treated with VEGF neutralizing antibodies also resulted in
      an attenuated expression of Kv2.1, Kv1.2, Kv1.4, Kir1.1, CCHL2a and SCN2a1
      channel mRNAs. CONCLUSIONS: GATA-4 overexpression increases Ito, IKDR, IK1,
      INa.TTX and ICa.L currents in MSC. Cytokine (VGEF and IGF-1) release from GATA-4
      overexpressing MSC can partially account for the upregulated ion channel mRNA
      expression. GENERAL SIGNIFICANCE: Our results highlight the ability of GATA4 to
      boost the cardiac electrophysiological potential of MSC.

PMID- 24582941
TI  - Role of emergency radiology in patient care: educating medical students and new
      trainees in emergency medicine.

PMID- 24582942
TI  - The short-shortsightedness of the new radiology boards.

PMID- 24582943
TI  - Intracellular trafficking of Clostridium botulinum C2 toxin.
AB  - Clostridium botulinum C2 toxin is a binary toxin composed of an enzymatic
      component (C2I) and binding component (C2II). The activated binding component
      (C2IIa) forms heptamers and the oligomer with C2I is taken up by receptor
      mediated endocytosis. We investigated the intracellular trafficking of C2 toxin.
      When MDCK cells were incubated with C2I and C2IIa at 37  degrees C, C2I
      colocalized with C2IIa in cytoplasmic vesicles at 5 min, and C2I then disappeared
      (15 min incubation and later), and C2IIa was observed in the vesicles.
      Internalized C2I and C2IIa were transported to early endosomes. Some of both
      components were returned to the plasma membrane through recycling endosomes,
      whereas the rest of C2IIa was transported to late endosomes and lysosomes for
      degradation. Bafilomycin A1, an endosomal acidification inhibitor, caused the
      accumulation of C2IIa in endosomes, and both nocodazole and colchicine,
      microtubule-disrupting agents, restricted C2IIa's movement in the cytosol. These
      results indicated that an internalized C2I and C2IIa complex was delivered to
      early endosomes, and that subsequent delivery of C2I to the cytoplasm occurred in
      early endosomes. C2IIa was either sent back to the plasma membranes through
      recycling endosomes or transported to late endosomes and lysosomes for
      degradation. 

PMID- 24582944
TI  - Loneliness among very old Mexican Americans: findings from the Hispanic
      Established Populations Epidemiologic Studies of the Elderly.
AB  - Increasing numbers of researchers are finding that loneliness is a significant
      risk factor for morbidity and mortality, and several variables have been found to
      be closely related to the experience of loneliness among elders. However, much of
      the research has focused on the general older population, with no research to
      date focusing on minority populations. The objective of this study was to
      determine the prevalence and the correlates of loneliness among a community
      dwelling older Mexican American population. This study used a three-item
      loneliness scale to determine the prevalence of loneliness. Pearson's correlation
      and linear regression analyses were used to determine the cross-sectional
      association between sociodemographic, interpersonal relationship and health
      variables with the scale. Data used came from the most recent wave (2011) of the
      Hispanic Established Populations for the Epidemiological Study of the Elderly (H
      EPESE). A total of 873 Mexican Americans completed the loneliness scale. The age
      range was from 80 to 102, with a majority (65%) female. The mean score on the
      scale was 4.05 (range 3-9), indicating relatively low levels of loneliness.
      Regression results indicate that depressive symptoms, cognitive status, and
      living alone were significantly associated with higher loneliness scores. Being
      married and having a confidante were significantly associated with lower
      loneliness. Age, number of close relatives and frequency of contact were not
      associated with loneliness. Findings suggest that among community-dwelling
      Mexican American older adults, loneliness has multiple determinants. Loneliness
      is a significant public health topic and clinicians should be aware of the
      various factors that can affect loneliness. 

PMID- 24582945
TI  - The relationship between total anticholinergic burden (ACB) and early in-patient
      hospital mortality and length of stay in the oldest old aged 90 years and over
      admitted with an acute illness.
AB  - The use of prescription drugs in older people is high and many commonly
      prescribed drugs have anticholinergic effects. We examined the relationship
      between ACB on mortality and in-patient length of stay in the oldest old
      hospitalised population. This was a retrospective analysis of prospective audit
      using hospital audit data from acute medical admissions in three hospitals in
      England and Scotland. Baseline use of possible or definite anticholinergics was
      determined according to the Anticholinergic Cognitive Burden Scale. The main
      outcome measures were decline in-hospital mortality, early in-hospital mortality
      at 3- and 7-days and in-patient length of stay. A total of 419 patients
      (including 65 patients with known dementia) were included [median age=92.9, inter
      quartile range (IQR) 91.4-95.1 years]. 256 (61.1%) were taking anticholinergic
      medications. Younger age, greater number of pre-morbid conditions, ischemic heart
      disease, number of medications, higher urea and creatinine levels were
      significantly associated with higher total ACB burden on univariate regression
      analysis. There were no significant differences observed in terms of in-patient
      mortality, in-patient hospital mortality within 3- and 7-days and likelihood of
      prolonged length of hospital stay between ACB categories. Compared to those
      without cardiovascular disease, patients with cardiovascular disease showed
      similar outcome regardless of ACB load (either =0 or >0 ACB). We found no
      association between ACB and early (within 3- and 7-days) and in-patient mortality
      and hospital length of stay outcomes in this cohort of oldest old in the acute
      medical admission setting. 

PMID- 24582946
TI  - Developing core outcome measurement sets for clinical trials: OMERACT filter 2.0.
AB  - BACKGROUND: Lack of standardization of outcome measures limits the usefulness of
      clinical trial evidence to inform health care decisions. This can be addressed by
      agreeing on a minimum core set of outcome measures per health condition,
      containing measures relevant to patients and decision makers. Since 1992, the
      Outcome Measures in Rheumatology (OMERACT) consensus initiative has successfully
      developed core sets for many rheumatologic conditions, actively involving
      patients since 2002. Its expanding scope required an explicit formulation of its
      underlying conceptual framework and process. METHODS: Literature searches and
      iterative consensus process (surveys and group meetings) of stakeholders
      including patients, health professionals, and methodologists within and outside
      rheumatology. RESULTS: To comprehensively sample patient-centered and
      intervention-specific outcomes, a framework emerged that comprises three core
      "Areas," namely Death, Life Impact, and Pathophysiological Manifestations; and
      one strongly recommended Resource Use. Through literature review and consensus
      process, core set development for any specific health condition starts by
      identifying at least one core "Domain" within each of the Areas to formulate the
      "Core Domain Set." Next, at least one applicable measurement instrument for each
      core Domain is identified to formulate a "Core Outcome Measurement Set." Each
      instrument must prove to be truthful (valid), discriminative, and feasible. In
      2012, 96% of the voting participants (n=125) at the OMERACT 11 consensus
      conference endorsed this model and process. CONCLUSION: The OMERACT Filter 2.0
      explicitly describes a comprehensive conceptual framework and a recommended
      process to develop core outcome measurement sets for rheumatology likely to be
      useful as a template in other areas of health care.

PMID- 24582948
TI  - The involvement of FAK and Src in the invasion of cardiomyocytes by Trypanosoma
      cruzi.
AB  - The activation of signaling pathways involving protein tyrosine kinases (PTKs)
      has been demonstrated during Trypanosoma cruzi invasion. Herein, we describe the
      participation of FAK/Src in the invasion of cardiomyocytes by T. cruzi. The
      treatment of cardiomyocytes with genistein, a PTK inhibitor, significantly
      reduced T. cruzi invasion. Also, PP1, a potent Src-family protein inhibitor, and
      PF573228, a specific FAK inhibitor, also inhibited T. cruzi entry; maximal
      inhibition was achieved at concentrations of 25MUM PP1 (53% inhibition) and 40MUM
      PF573228 (50% inhibition). The suppression of FAK expression in siRNA-treated
      cells and tetracycline-uninduced Tet-FAK(WT)-46 cells significantly reduced T.
      cruzi invasion. The entry of T. cruzi is accompanied by changes in FAK and c-Src
      expression and phosphorylation. An enhancement of FAK activation occurs during
      the initial stages of T. cruzi-cardiomyocyte interaction (30 and 60min), with a
      concomitant increase in the level of c-Src expression and phosphorylation,
      suggesting that FAK/Src act as an integrated signaling pathway that coordinates
      parasite entry. These data provide novel insights into the signaling pathways
      that are involved in cardiomyocyte invasion by T. cruzi. A better understanding
      of the signal transduction networks involved in T. cruzi invasion may contribute
      to the development of more effective therapies for the treatment of Chagas'
      disease. 

PMID- 24582947
TI  - Factors that affect efficacy of ultrasound surveillance for early stage
      hepatocellular carcinoma in patients with cirrhosis.
AB  - BACKGROUND & AIMS: Ultrasound surveillance does not detect early stage
      hepatocellular carcinomas (HCCs) in some patients with cirrhosis, although the
      reasons for this have not been well studied. We assessed the rate at which
      ultrasound fails to detect early stage HCCs and factors that affect its
      performance. METHODS: We collected information on 1170 consecutive patients
      included in the Italian Liver Cancer (ITA.LI.CA) database who had Child-Pugh A or
      B cirrhosis and were diagnosed with HCC during semiannual or annual ultrasound
      surveillance, from January 1987 through December 2008. Etiologies included
      hepatitis C virus infection (59.3%), alcohol abuse (11.3%), hepatitis B virus
      infection (9%), a combination of factors (15.6%), and other factors (4.7%).
      Surveillance was considered to be a failure when patients were diagnosed with HCC
      at a stage beyond the Milan criteria (1 nodule <=5 cm or <=3 nodules each <=3
      cm). RESULTS: HCC was found beyond Milan criteria in 34.3% of surveilled patients
      (32.2% during semi-annual surveillance and 41.3% during annual surveillance; P <
      .01). Nearly half of surveillance failures were associated with at least one
      indicator of aggressive HCC (levels of AFP >1000 ng/mL, infiltrating tumors, or
      vascular invasion and metastases). Semiannual surveillance, female sex, Child
      Pugh class A, and alpha-fetoprotein levels of 200 ng/mL or less were associated
      independently with successful ultrasound screening for HCC. CONCLUSIONS: Based on
      our analysis of surveillance for HCC in patients with cirrhosis, the efficacy of
      ultrasound-based screening is acceptable. Ultrasound was least effective in
      identifying aggressive HCC, and at surveillance intervals of more than 6 months.

PMID- 24582949
TI  - Genome-wide analysis of single nucleotide polymorphisms and copy number variants
      in fibromyalgia suggest a role for the central nervous system.
AB  - Fibromyalgia (FM) is a highly disabling syndrome defined by a low pain threshold
      and a permanent state of pain. The mechanisms explaining this complex disorder
      remain unclear, and its genetic factors have not yet been identified. With the
      aim of elucidating FM genetic susceptibility factors, we selected 313 FM cases
      having low comorbidities, and we genotyped them on the Illumina 1 million duo
      array. Genotypic data from 220 control women (Illumina 610k array) was obtained
      for genome-wide association scan (GWAS) analysis. Copy number variants in FM
      susceptibility were analyzed by array comparative genomic hybridization (aCGH)
      experiments on pooled samples using the Agilent 2*400K platform. No single
      nucleotide polymorphism (SNP) reached GWAS association threshold, but 21 of the
      most associated SNPs were chosen for replication in 952 cases and 644 controls.
      Four of the SNPs selected for replication showed a nominal association in the
      joint analysis, and rs11127292 (MYT1L) was found to be associated to FM with low
      comorbidities (P=4.28*10(-5), odds ratio [95% confidence interval]=0.58 [0.44
      0.75]). aCGH detected 5 differentially hybridized regions. They were followed up,
      and an intronic deletion in NRXN3 was demonstrated to be associated to female
      cases of FM with low levels of comorbidities (P=.021, odds ratio [95% confidence
      interval]=1.46 [1.05-2.04]). Both GWAS and aCGH results point to a role for the
      central nervous system in FM genetic susceptibility. If the proposed FM candidate
      genes were further validated in replication studies, this would highlight a
      neurocognitive involvement in agreement with latest reports. 

PMID- 24582950
TI  - Aerobic granulation in a modified oxidation ditch with an adjustable volume
      intraclarifier.
AB  - A modified oxidation ditch (MOD) with an adjustable volume intraclarifier was
      proposed and used to achieve aerobic sludge granulation in continuous flow
      process. This MOD with working volume of 60L treated onsite wastewater from a
      town. Excellent aerobic granules with mean diameter of 600MUm and sludge volume
      index (SVI) of 44mL/g were obtained in 120day. Bacterial community analysis
      revealed that most species from seed sludge were preserved in both MOD and
      granule SBR (G-SBR) except bacteria (Bacteroidetes) might be easily washed out
      during granulation. Some different bacterial communities were found in sludges
      from sequencing batch and continuous flow reactors. Presence of metal ions and
      inorganics in raw wastewater had positive effect on granule formation, but an
      adjustable volume intraclarifier for controlling selection pressure and deleting
      return sludge pump played a key role in aerobic sludge granulation. 

PMID- 24582951
TI  - Integration of the first and second generation bioethanol processes and the
      importance of by-products.
AB  - Lignocellulosic ethanol has obstacles in the investment costs and uncertainties
      in the process. One solution is to integrate it with the running dry mills of
      ethanol from grains. However, the economy of these mills, which dominate the
      world market, are dependent on their by-products DDGS (Distiller's Dried Grains
      and Solubles), sold as animal feed. The quality of DDGS therefore must not be
      negatively influenced by the integration. This puts restraints on the choice of
      pretreatment of lignocelluloses and utilizing the pentose sugars by food-grade
      microorganisms. The proposed solution is to use food related filamentous
      Zygomycetes and Ascomycetes fungi, and to produce fungal biomass as a high-grade
      animal feed from the residues after the distillation (stillage). This also has
      the potential to improve the first generation process by increasing the amount of
      the thin stillage directly sent back into the process, and by decreasing the
      evaporator based problems. 

PMID- 24582952
TI  - Evaluation of a thermo-tolerant acidophilic alga, Galdieria sulphuraria, for
      nutrient removal from urban wastewaters.
AB  - Nutrient removal from primary wastewater effluent was tested using Galdieria
      sulphuraria, an acidophilic and moderately thermophilic alga. Biomass yield
      recorded in this study (27.42g biomass per g nitrogen removed) is higher than the
      average reported in the literature (25.75g g(-1)) while, the theoretical yield
      estimated from the empirical molecular formula of algal biomass is 15.8g g(-1).
      Seven-day removal efficiencies were 88.3% for ammoniacal-nitrogen and 95.5% for
      phosphates; corresponding removal rates were 4.85 and 1.21mg L(-1)d(-1). Although
      these rates are lower than the average literature values for other strains (6.36
      and 1.34mg L(-1)d(-1), respectively), potential advantages of G. sulphuraria for
      accomplishing energy-positive nutrient removal are highlighted. Feasibility of
      growing G. sulphuraria outdoors at densities higher than in high-rate oxidation
      ponds is also demonstrated.

PMID- 24582953
TI  - Thermodynamic analysis of thymoquinone binding to human serum albumin.
AB  - The interaction of thymoquinone (TQ) with human serum albumin (HAS) in
      physiological buffer (pH=7.0) was studied at four temperatures in the range 25-50
      degrees C using fluorescence quenching study. The binding parameters were
      determined by Scatchard and Stern-Volmer models. Fluorescence quenching data
      revealed that the binding constants (Ksc) are 1.71*10(4), 1.08*10(4), 1.03*10(4)
      and 0.969*10(4) M(-1) at 298, 303, 313 and 323 K, respectively (on the basis of
      Scatchard model). The thermodynamic parameters DeltaG degrees , DeltaH degrees 
      and DeltaS degrees  were calculated the results indicated that the hydrogen
      bonding and hydrophobic interactions were the predominant intermolecular factors
      in stabilizing the TQ-HSA complex. The distance between donor (HSA) and acceptor
      (TQ) was calculated to be 3.26 nm based on Forster's non-radiative energy
      transfer theory.

PMID- 24582954
TI  - A glenoid reaming study: how accurate are current reaming techniques?
AB  - BACKGROUND: Correct reaming of a degenerative glenoid can be a difficult
      procedure. We investigated how the quality of the reamed surface is influenced by
      different reamers, by the surgeon's experience, and by glenoid erosion patterns.
      MATERIAL AND METHODS: Three shoulder surgeons performed reaming procedures with
      different types of reamers (flat, convex, K-wire guided, and nipple guided) on a
      series of similarly sized uniconcave and biconcave glenoids. The reproducibility
      of reaming and the effect of different reamers on different-shaped glenoids were
      measured and evaluated. RESULTS: The center and direction of reaming were
      constant for all surgeons in the case of type A glenoids. For type B2 glenoids,
      the center and direction of reaming differed significantly between surgeons. The
      congruity of the reamed surface was better after flat reaming than after convex
      reaming. Whether the reamers were guided by a central K-wire or by a nipple had
      no significant effect on the reamed surface. The experience of the surgeon had no
      effect on the congruity of reaming. CONCLUSIONS: Reaming of a uniconcave glenoid
      is reproducible, but reaming of a biconcave glenoid seems much more difficult.
      Erosion and deformity of the glenoid influence the accuracy of reaming the most.
      Surgical experience plays a less important role. We conclude that there is a need
      for guidance in reaming of biconcave glenoids.

PMID- 24582955
TI  - Application of the fulcrum axis to estimate the central scapular axis.
AB  - BACKGROUND: Glenoid resurfacing can be a challenging component of total shoulder
      arthroplasty when significant glenoid retroversion or deformity is present. The
      purpose of this study was to determine whether a newly designed glenoid-targeting
      guide using the parallel relationship between glenoid version and an anatomic
      fulcrum axis could accurately estimate the central axis of the scapula. MATERIALS
      AND METHODS: Three orthopaedic surgeons used a newly designed glenoid-targeting
      guide to place a guide pin into 6 normal Sawbones scapulae (Pacific Research
      Laboratories, Vashon Island, WA, USA), 6 retroverted Sawbones scapulae, 8
      cadaveric scapular specimens, and 5 cadaveric shoulder specimens. Angles of
      deviation from the central scapular axis and from perpendicular to the fulcrum
      axis were measured. RESULTS: The mean pin deviation angle from the central
      scapular axis and the mean fulcrum deviation angle for the normal Sawbones
      scapulae were 1.7 degrees  (SD, 1.2 degrees ) and 2.1 degrees  (SD, 1.5 degrees
      ), respectively. For altered retroverted Sawbones scapulae, the mean deviation
      angles were 1.8 degrees  (SD, 1.2 degrees ) and 2.8 degrees  (SD, 1.6 degrees ),
      respectively. The combined mean pin deviation angle and mean fulcrum deviation
      angle for cadaveric shoulder specimens were 2.8 degrees  (SD, 3.3 degrees ) and
      2.3 degrees  (SD, 2.3 degrees ), respectively. The surgeons' results did not
      differ significantly whether using Sawbones models, cadaveric scapular specimens,
      or cadaveric shoulder specimens. CONCLUSION: A glenoid-targeting guide based on
      the relationship of the fulcrum axis and glenoid version can be used to
      accurately estimate the central scapular axis. Such a tool can be accurate and
      reliable intraoperatively, aiding in glenoid component placement to within 5
      degrees  of ideal version, irrespective of glenoid deformity.

PMID- 24582956
TI  - Reliability of the posterolateral corner of the acromion as a landmark for the
      posterior arthroscopic portal of the shoulder.
AB  - HYPOTHESIS: The present study aimed to evaluate the variability of the
      posterolateral corner of the acromion (PCA) position in relation to the
      glenohumeral joint, in a craniocaudal direction, to assess whether the universal
      use of a certain distance from that point will always lead to a consistent
      placement of the posterior arthroscopic portal of the shoulder. METHODS: The
      study used 140 dried scapulae (36 women and 34 men). Measurements included the
      glenoid height and the perpendicular distance between the PCA and the most
      superior point of the glenoid. The percentage of coverage of the glenoid by the
      acromion was defined as the ratio between the 2 measurements. The Student t test
      was used to examine for significant differences between the sexes and the Student
      paired t test between sides (P < .05). RESULTS: The average glenoid height was
      3.37 +/- 0.29 cm (range, 2.69-4.00 cm). The perpendicular distance between the
      PCA and the most superior point of the glenoid was 0.82 +/- 0.69 cm (range, -0.35
      to 2.27 cm). The percentage of coverage of the glenoid by the acromion was 24% +/
      20% (range, -10% to 64%). CONCLUSIONS: The position of the PCA in relation to
      the glenohumeral joint is quite variable. Therefore, the use of a universal
      distance from the PCA will not always lead to a consistent placement of the
      posterior arthroscopic portal of the shoulder. Future research is needed in this
      area to develop techniques to individualize placement of the posterior portal.

PMID- 24582957
TI  - The SIRT1 activator SRT1720 extends lifespan and improves health of mice fed a
      standard diet.
AB  - The prevention or delay of the onset of age-related diseases prolongs survival
      and improves quality of life while reducing the burden on the health care system.
      Activation of sirtuin 1 (SIRT1), an NAD(+)-dependent deacetylase, improves
      metabolism and confers protection against physiological and cognitive
      disturbances in old age. SRT1720 is a specific SIRT1 activator that has health
      and lifespan benefits in adult mice fed a high-fat diet. We found extension in
      lifespan, delayed onset of age-related metabolic diseases, and improved general
      health in mice fed a standard diet after SRT1720 supplementation. Inhibition of
      proinflammatory gene expression in both liver and muscle of SRT1720-treated
      animals was noted. SRT1720 lowered the phosphorylation of NF-kappaB pathway
      regulators in vitro only when SIRT1 was functionally present. Combined with our
      previous work, the current study further supports the beneficial effects of
      SRT1720 on health across the lifespan in mice.

PMID- 24582958
TI  - Sensory-driven enhancement of calcium signals in individual Purkinje cell
      dendrites of awake mice.
AB  - Climbing fibers (CFs) are thought to contribute to cerebellar plasticity and
      learning by triggering a large influx of dendritic calcium in the postsynaptic
      Purkinje cell (PC) to signal the occurrence of an unexpected sensory event.
      However, CFs fire about once per second whether or not an event occurs, raising
      the question of how sensory-driven signals might be distinguished from a
      background of ongoing spontaneous activity. Here, we report that in PC dendrites
      of awake mice, CF-triggered calcium signals are enhanced when the trigger is a
      sensory event. In addition, we show that a large fraction of the total
      enhancement in each PC dendrite can be accounted for by an additional boost of
      calcium provided by sensory activation of a non-CF input. We suggest that sensory
      stimulation may modulate dendritic voltage and calcium concentration in PCs to
      increase the strength of plasticity signals during cerebellar learning.

PMID- 24582959
TI  - Selective protection of an ARF1-GTP signaling axis by a bacterial scaffold
      induces bidirectional trafficking arrest.
AB  - Bidirectional vesicular transport between the endoplasmic reticulum (ER) and
      Golgi is mediated largely by ARF and Rab GTPases, which orchestrate vesicle
      fission and fusion, respectively. How their activities are coordinated in order
      to define the successive steps of the secretory pathway and preserve traffic
      directionality is not well understood in part due to the scarcity of molecular
      tools that simultaneously target ARF and Rab signaling. Here, we take advantage
      of the unique scaffolding properties of E. coli secreted protein G (EspG) to
      describe the critical role of ARF1/Rab1 spatiotemporal coordination in vesicular
      transport at the ER-Golgi intermediate compartment. Structural modeling and
      cellular studies show that EspG induces bidirectional traffic arrest by tethering
      vesicles through select ARF1-GTP/effector complexes and local inactivation of
      Rab1. The mechanistic insights presented here establish the effectiveness of a
      small bacterial catalytic scaffold for studying complex processes and reveal an
      alternative mechanism of immune regulation by an important human pathogen.

PMID- 24582961
TI  - Cysteine proteinase-1 and cut protein isoform control dendritic innervation of
      two distinct sensory fields by a single neuron.
AB  - Dendrites often exhibit structural changes in response to local inputs. Although
      mechanisms that pattern and maintain dendritic arbors are becoming clearer,
      processes regulating regrowth, during context-dependent plasticity or after
      injury, remain poorly understood. We found that a class of Drosophila sensory
      neurons, through complete pruning and regeneration, can elaborate two distinct
      dendritic trees, innervating independent sensory fields. An expression screen
      identified Cysteine proteinase-1 (Cp1) as a critical regulator of this process.
      Unlike known ecdysone effectors, Cp1-mutant ddaC neurons pruned larval dendrites
      normally but failed to regrow adult dendrites. Cp1 expression was
      upregulated/concentrated in the nucleus during metamorphosis, controlling
      production of a truncated Cut homeodomain transcription factor. This truncated
      Cut, but not the full-length protein, allowed Cp1-mutant ddaC neurons to
      regenerate higher-order adult dendrites. These results identify a molecular
      pathway needed for dendrite regrowth after pruning, which allows the same neuron
      to innervate distinct sensory fields. 

PMID- 24582960
TI  - Pten loss induces autocrine FGF signaling to promote skin tumorigenesis.
AB  - Inactivation of the Pten tumor suppressor negatively regulates the PI3K-mTOR
      pathway. In a model of cutaneous squamous cell carcinoma (SCC), we demonstrate
      that deletion of Pten strongly elevates Fgf10 protein levels without increasing
      Fgf10 transcription in vitro and in vivo. The translational activation of Fgf10
      by Pten deletion is reversed by genetic disruption of the mTORC1 complex, which
      also prevents skin tumorigenesis in Pten mutants. We further show that ectopic
      expression of Fgf10 causes skin papillomas, whereas Pten deletion-induced skin
      tumors are inhibited by epidermal deletion of Fgfr2. Collectively, our data
      identify autocrine activation of FGF signaling as an essential mechanism in
      promoting Pten-deficient skin tumors.

PMID- 24582962
TI  - miR-146a and miR-155 delineate a MicroRNA fingerprint associated with Toxoplasma
      persistence in the host brain.
AB  - microRNAs were recently found to be regulators of the host response to infection
      by apicomplexan parasites. In this study, we identified two immunomodulatory
      microRNAs, miR-146a and miR-155, that were coinduced in the brains of mice
      challenged with Toxoplasma in a strain-specific manner. These microRNAs define a
      characteristic fingerprint for infection by type II strains, which are the most
      prevalent cause of human toxoplasmosis in Europe and North America. Using forward
      genetics, we showed that strain-specific differences in miR-146a modulation were
      in part mediated by the rhoptry kinase, ROP16. Remarkably, we found that miR-146a
      deficiency led to better control of parasite burden in the gut and most likely of
      early parasite dissemination in the brain tissue, resulting in the long-term
      survival of mice.

PMID- 24582963
TI  - Recapitulation of developing artery muscularization in pulmonary hypertension.
AB  - Excess smooth muscle accumulation is a key component of many vascular disorders,
      including atherosclerosis, restenosis, and pulmonary artery hypertension, but the
      underlying cell biological processes are not well defined. In pulmonary artery
      hypertension, reduced pulmonary artery compliance is a strong independent
      predictor of mortality, and pathological distal arteriole muscularization
      contributes to this reduced compliance. We recently demonstrated that embryonic
      pulmonary artery wall morphogenesis consists of discrete developmentally
      regulated steps. In contrast, poor understanding of distal arteriole
      muscularization in pulmonary artery hypertension severely limits existing
      therapies that aim to dilate the pulmonary vasculature but have modest clinical
      benefit and do not prevent hypermuscularization. Here, we show that most
      pathological distal arteriole smooth muscle cells, but not alveolar
      myofibroblasts, derive from pre-existing smooth muscle. Furthermore, the program
      of distal arteriole muscularization encompasses smooth muscle cell
      dedifferentiation, distal migration, proliferation, and then redifferentiation,
      thereby recapitulating many facets of arterial wall development. 

PMID- 24582964
TI  - Transformed epithelia trigger non-tissue-autonomous tumor suppressor response by
      adipocytes via activation of Toll and Eiger/TNF signaling.
AB  - High tumor burden is associated with increased levels of circulating inflammatory
      cytokines that influence the pathophysiology of the tumor and its environment.
      The cellular and molecular events mediating the organismal response to a growing
      tumor are poorly understood. Here, we report a bidirectional crosstalk between
      epithelial tumors and the fat body-a peripheral immune tissue-in Drosophila.
      Tumors trigger a systemic immune response through activation of Eiger/TNF
      signaling, which leads to Toll pathway upregulation in adipocytes. Reciprocally,
      Toll elicits a non-tissue-autonomous program in adipocytes, which drives tumor
      cell death. Hemocytes play a critical role in this system by producing the
      ligands Spatzle and Eiger, which are required for Toll activation in the fat body
      and tumor cell death. Altogether, our results provide a paradigm for a long-range
      tumor suppression function of adipocytes in Drosophila, which may represent an
      evolutionarily conserved mechanism in the organismal response to solid tumors. 

PMID- 24582966
TI  - The Wnt/planar cell polarity pathway component Vangl2 induces synapse formation
      through direct control of N-cadherin.
AB  - Although regulators of the Wnt/planar cell polarity (PCP) pathway are widely
      expressed in vertebrate nervous systems, their roles at synapses are unknown.
      Here, we show that Vangl2 is a postsynaptic factor crucial for synaptogenesis and
      that it coprecipitates with N-cadherin and PSD-95 from synapse-rich brain
      extracts. Vangl2 directly binds N-cadherin and enhances its internalization in a
      Rab5-dependent manner. This physical and functional interaction is suppressed by
      beta-catenin, which binds the same intracellular region of N-cadherin as Vangl2.
      In hippocampal neurons expressing reduced Vangl2 levels, dendritic spine
      formation as well as synaptic marker clustering is significantly impaired.
      Furthermore, Prickle2, another postsynaptic PCP component, inhibits the N
      cadherin-Vangl2 interaction and is required for normal spine formation. These
      results demonstrate direct control of classic cadherin by PCP factors; this
      control may play a central role in the precise formation and maturation of cell
      cell adhesions at the synapse. 

PMID- 24582965
TI  - Histone demethylase RBP2 is critical for breast cancer progression and
      metastasis.
AB  - Metastasis is a major clinical challenge for cancer treatment. Emerging evidence
      suggests that aberrant epigenetic modifications contribute significantly to tumor
      formation and progression. However, the drivers and roles of such epigenetic
      changes in tumor metastasis are still poorly understood. Using bioinformatic
      analysis of human breast cancer gene-expression data sets, we identified histone
      demethylase RBP2 as a putative mediator of metastatic progression. By using both
      human breast cancer cells and genetically engineered mice, we demonstrated that
      RBP2 is critical for breast cancer metastasis to the lung in multiple in vivo
      models. Mechanistically, RBP2 promotes metastasis as a pleiotropic positive
      regulator of many metastasis genes, including TNC. In addition, RBP2 loss
      suppresses tumor formation in MMTV-neu transgenic mice. These results suggest
      that therapeutic targeting of RBP2 is a potential strategy for inhibition of
      tumor progression and metastasis. 

PMID- 24582967
TI  - Recombinant human soluble thrombomodulin attenuates FK506-induced endothelial
      dysfunction through prevention of Akt inactivation.
AB  - Thrombomodulin (TM), a transmembrane glycoprotein on vascular endothelial cells,
      is a naturally occurring anticoagulant. Recombinant human soluble TM (rTM),
      composed of the extracellular domain of TM, also shows anti-coagulant and anti
      inflammatory activity, but the effects of rTM on microangiopathy remain unclear.
      We reported that FK506 induced endothelial dysfunction through inactivation of
      Akt and extracellular-regulated kinase 1/2 using a three-dimensional culture
      blood vessel model. In the present study, we examined the effects of rTM on FK506
      induced endothelial dysfunction. We found that rTM suppressed FK506-induced
      endothelial cell death, but not the breakdown of capillary-like tube structures.
      rTM prevented FK506-induced inactivation of Akt, but not of extracellular
      regulated kinase 1/2. Akt inhibition by LY294002 abrogated the preventive effect
      of rTM on FK506-induced Akt inactivation and the suppressive effect of rTM on
      FK506-induced cell death. These results suggest that rTM attenuates FK506-induced
      endothelial dysfunction through prevention of Akt inactivation.

PMID- 24582969
TI  - Heat shock proteins in fibrosis and wound healing: good or evil?
AB  - Heat shock proteins (HSPs) are key regulators of cell homeostasis, and their
      cytoprotective role has been largely investigated in the last few decades.
      However, an increasing amount of evidence highlights their deleterious effects on
      several human pathologies, including cancer, in which they promote tumor cell
      survival, proliferation and drug resistance. Therefore, HSPs have recently been
      suggested as therapeutic targets for improving human disease outcomes. Fibrotic
      diseases and cancer share several properties; both pathologies are characterized
      by genetic alterations, uncontrolled cell proliferation, altered cell
      interactions and communication and tissue invasion. The discovery of new HSP
      inhibitors that have been shown to be efficacious against certain types of
      cancers has given rise to a new field of research that investigates the activity
      of these compounds in other incurable human diseases such as fibrotic disorders.
      The aim of this review is to discuss new findings regarding the involvement of
      HSPs in the pathogenesis of organ fibrosis and to note recent discoveries that
      indicate that HSPs could be important therapeutic targets to improve the current
      dismal outcome of fibrotic diseases. 

PMID- 24582970
TI  - Dynamic interplay between breast cancer cells and normal endothelium mediates the
      expression of matrix macromolecules, proteasome activity and functional
      properties of endothelial cells.
AB  - BACKGROUND: Breast cancer-endothelium interactions provide regulatory signals
      facilitating tumor progression. The endothelial cells have so far been mainly
      viewed in the context of tumor perfusion and relatively little is known regarding
      the effects of such paracrine interactions on the expression of extracellular
      matrix (ECM), proteasome activity and properties of endothelial cells. METHODS:
      To address the effects of breast cancer cell (BCC) lines MDA-MB-231 and MCF-7 on
      the endothelial cells, two cell culture models were utilized; one involves
      endothelial cell culture in the presence of BCCs-derived conditioned media (CM)
      and the other co-culture of both cell populations in a Transwell system. Real
      time PCR was utilized to evaluate gene expression, an immunofluorescence assay
      for proteasome activity, and functional assays (migration, adhesion and invasion)
      and immunofluorescence microscopy for cell integrity and properties. RESULTS: BCC
      CM decreases the cell migration of HUVEC. Adhesion and invasion of BCCs are
      favored by HUVEC and HUVEC-CM. HA levels and the expression of CD44 and HA
      synthase-2 by HUVEC are substantially upregulated in both cell culture
      approaches. Adhesion molecules, ICAM-1 and VCAM-1, are also highly upregulated,
      whereas MT1-MMP and MMP-2 expressions are significantly downregulated in both
      culture systems. Notably, the expression and activity of the proteasome beta5
      subunit are increased, especially by the action of MDA-MB-231-CM on HUVEC.
      CONCLUSIONS AND GENERAL SIGNIFICANCE: BCCs significantly alter the expression of
      matrix macromolecules, proteasome activity and functional properties of
      endothelial cells. Deep understanding of such paracrine interactions will help to
      design novel drugs targeting breast cancer at the ECM level. This article is part
      of a Special Issue entitled Matrix-mediated cell behaviour and properties.

PMID- 24582971
TI  - Transcription factor Runx1 inhibits proliferation and promotes developmental
      maturation in a selected population of inner olfactory nerve layer olfactory
      ensheathing cells.
AB  - The olfactory system undergoes persistent regeneration throughout life. Olfactory
      ensheathing cells (OECs) are a specialized class of glia found exclusively in the
      olfactory system. OECs wrap olfactory sensory neuron axons and support their
      growth from the olfactory epithelium, and targeting to the olfactory bulb, during
      development and life-long regeneration. Because of this function and their
      ability to cross the boundary between central and peripheral nervous systems,
      OECs are attractive candidates for cell-based regenerative therapies to promote
      axonal repair in the injured nervous system. OECs are a molecularly,
      topologically and functionally heterogeneous group of cells and the mechanisms
      underlying the development and function of specific OEC subpopulations are poorly
      defined. This situation has affected the outcome and interpretation of OEC-based
      regenerative strategies. Here we show that the transcription factor Runx1 is
      selectively expressed in OECs of the inner olfactory nerve layer of the mouse
      olfactory bulb and in their precursors in the OEC migratory mass. Furthermore, we
      provide evidence that in vivo knockdown of mouse Runx1 increases the
      proliferation of the OECs in which Runx1 is expressed. Conversely, Runx1
      overexpression in primary cultures of OECs reduces cell proliferation in vitro.
      Decreased Runx1 activity also leads to an increase in Runx1-expressing OEC
      precursors, with a parallel decrease in the number of more developmentally mature
      OECs. These results identify Runx1 as a useful new marker of a distinct OEC
      subpopulation and suggest that Runx1 is important for the development of this
      group of OECs. These observations provide an avenue for further exploration into
      the molecular mechanisms underlying the development and function of specific OEC
      subpopulations. 

PMID- 24582972
TI  - Sex- and age-dependent effects of Gpr30 genetic deletion on the metabolic and
      cardiovascular profiles of diet-induced obese mice.
AB  - The G protein-coupled receptor 30 (GPR30) has been claimed as an estrogen
      receptor. However, the literature reports controversial findings and the
      physiological function of GPR30 is not fully understood yet. Consistent with
      studies assigning a role of GPR30 in the cardiovascular and metabolic systems,
      GPR30 expression has been reported in small arterial vessels, pancreas and chief
      gastric cells of the stomach. Therefore, we hypothesized a role of GPR30 in the
      onset and progression of cardiovascular and metabolic diseases. In order to test
      our hypothesis, we investigated the effects of a high-fat diet on the metabolic
      and cardiovascular profiles of Gpr30-deficient mice (GPR30-lacZ mice). We found
      that GPR30-lacZ female, rather than male, mice had significant lower levels of
      HDL along with an increase in fat liver accumulation as compared to control mice.
      However, two indicators of cardiac performance assessed by echocardiography,
      ejection fraction and fractional shortening were both decreased in an age
      dependent manner only in Gpr30-lacZ male mice. Collectively our results point to
      a potential role of Gpr30 in preserving lipid metabolism and cardiac function in
      a sex- and age-dependent fashion. 

PMID- 24582973
TI  - Genome wide DNA methylation profiling for epigenetic alteration in coronary
      artery disease patients.
AB  - BACKGROUND: The alteration in the epigenome forms an interface between the
      genotype and the environment. Epigenetic alteration is expected to make a
      significant contribution to the development of cardiovascular disease where
      environmental interactions play a key role in disease progression. We had
      previously shown that global DNA hypermethylation per se is associated with
      coronary artery disease (CAD) and is further accentuated by high levels of
      homocysteine, a thiol amino acid which is an independent risk factor for
      cardiovascular disease and is also a key modulator of macromolecular methylation.
      RESULTS: We have identified 72 differentially methylated regions (DMRs) that were
      hypermethylated in CAD patients in the background of varying homocysteine levels.
      Following deep bisulfite sequencing of a few of the selected DMRs, we found
      significantly higher methylation in CAD cases. We get six CpG sites in three DMRs
      that included the intronic region of C1QL4 gene and upstream region of CCDC47 and
      TGFBR3 genes. CONCLUSION: To the best of our knowledge, this is the first study
      to identify hypermethylated regions across the genome in patients with coronary
      artery disease. Further validation in different populations is necessary for this
      information to be used for disease risk assessment and management.

PMID- 24582974
TI  - A new design without control population for identification of gastric cancer
      related allele combinations based on interaction of genes.
AB  - OBJECTIVE: The purpose of this study was to develop a novel approach without
      control population to examine the relationship between the presence of specific
      allele combinations at different loci with the onset of gastric cancer. METHODS:
      DNA samples were collected from patients with gastric cancer. Alleles from short
      tandem repeat loci were determined using the STR Profiler Plus PCR amplification
      kit (15 STR loci). The observed and expected frequencies of specific allele
      combinations were calculated; statistically significant allele combinations were
      identified by comparing the observed frequency with the expected frequency. The
      age at disease onset of patients carrying a specific allele combination was
      further analysed; allele combinations related to the gastric cancer were
      effectively identified from the large number of possible allele combinations by
      cross-validation of the 2 sets of analytical results. RESULTS: A total of 2209
      pairwise combinations were obtained by computer counting, of which 11 pairs of
      genes showed significant differences between the observed and expected
      frequencies (p<0.05). The p value for the cross-validation was also less than
      0.05 for 2 pair of alleles (D8S1179-16 and D5S818-13; D2S1338-23 and D6S1043-11).
      CONCLUSION: Gastric cancer onset may be associated with these allele
      combinations. The new methodology without control group will enable additional
      discoveries pertaining to the relationship between specific allele combinations
      at different loci and the onset of complex diseases.

PMID- 24582975
TI  - Laryngeal cancer risk and common single nucleotide polymorphisms in nucleotide
      excision repair pathway genes ERCC1, ERCC2, ERCC3, ERCC4, ERCC5 and XPA.
AB  - Because the molecular mechanisms underlying the development of laryngeal cancer
      are not well understood, we conducted a case-control study to determine the
      association between eight common SNPs in NER pathway genes and risk of laryngeal
      cancer, and the association between genetic polymorphisms and environmental
      factors. A 1:1 matched case-control study of 176 cases and 176 controls was
      conducted. Laryngeal cancer cases were more likely to smoke and drink (all P
      values<0.05). Subjects with the ERCC1 rs11615 CC genotype and C allele had an
      increased risk of laryngeal cancer. Similarly, individuals with the ERCC5 rs17655
      GG genotype and G allele had an increased risk of laryngeal cancer. Gene-gene
      interaction analysis showed that subjects carrying ERCC1 rs11615 C allele and
      XPG/ERCC5 rs17655 G allele had a greatly increased risk of breast cancer.
      Stratified analysis revealed that the interaction between polymorphisms of ERCC1
      rs11615 and ERCC5 rs17655 and smoking on cancer risk was statistically
      significant, and ERCC1 rs11615 polymorphisms also had a significant interaction
      with drinking habit. In conclusion, our study suggests that ERCC1 rs11615 and
      ERCC5 rs17655 polymorphisms are associated with increased risk of laryngeal
      cancer, and that they confer more risk among smokers and drinkers. 

PMID- 24582976
TI  - Novel ovine polymorphisms and adaptive evolution in mammalian TLR2 suggest
      existence of multiple pathogen binding regions.
AB  - Toll-like receptors initiate inflammatory responses following the recognition of
      a wide repertoire of pathogens including bacteria, fungi, protozoa and viruses.
      They are composed of an extracellular leucine-rich repeat domain responsible for
      detecting pathogen-associated molecular patterns, a membrane spanning region and
      an intracellular Toll/Interleukin 1 receptor domain which invokes signal
      transduction. Toll-like receptor 2 is the most diverse of these receptors as it
      recognises infectious agents from a range of pathogenic groups. Over 1400 breeds
      of sheep exist worldwide that inhabit a diverse range of environments, which
      leads to the potential contact with a wide variety of pathogens likely detected
      by Toll-like receptor 2. In this study, we evaluated the extent of both long term
      evolutionary changes, across the mammalian phylogeny of the TLR2 gene, and recent
      divergence of this same gene in sheep breeds. Evolutionary analyses identified
      positive selective pressure across the mammalian phylogeny, and differential
      selection pressure within the artiodactyl and primate lineage. Finally, we
      identified localised positively-selected sites within two regions of the
      extracellular domain which suggest that multiple binding regions in TLR2 may be
      involved in pathogen detection. These results are consistent with the hypothesis
      that competition between host and pathogen is driving adaptation of Toll-like
      receptor 2 genes. 

PMID- 24582977
TI  - Mitochondria and copper homeostasis in plants.
AB  - Copper (Cu) and other transition metals are essential for living organisms but
      also toxic when present in excess. To cope with this apparent paradox, organisms
      have developed sophisticated mechanisms to acquire, transport and store these
      metals. Particularly, plant mitochondria require Cu for the assembly and function
      of cytochrome c oxidase (COX), the terminal enzyme of the respiratory chain. COX
      assembly is a complex process that requires the action of multiple factors, many
      of them involved in the delivery and insertion of Cu into the enzyme. In this
      review, we summarize what is known about the processes involved in Cu delivery to
      mitochondria and how these processes impact in Cu homeostasis at the cellular
      level. We also discuss evidence indicating that metallochaperones involved in COX
      assembly play additional roles in signaling pathways related to changes in Cu and
      redox homeostasis and the response of plants to stress. We propose that cysteine
      rich proteins present in the mitochondrial intermembrane space are excellent
      candidates as sensors of these changes and transducers of signals originated in
      the organelle to the rest of the cell. 

PMID- 24582978
TI  - Chronic constipation recognized as a sign of a SOX10 mutation in a patient with
      Waardenburg syndrome.
AB  - Waardenburg syndrome is characterized by hearing loss, pigmentation
      abnormalities, dysmorphologic features, and neurological phenotypes. Waardenburg
      syndrome consists of four distinct subtypes, and SOX10 mutations have been
      identified in type II and type IV. Type IV differs from type II owing to the
      presence of Hirschsprung disease. We identified a de novo nonsense mutation in
      SOX10 (p.G39X) in a female pediatric patient with Waardenburg syndrome with
      heterochromia iridis, profound bilateral sensorineural hearing loss, inner ear
      malformations, and overall hypopigmentation of the hair without dystopia
      canthorum. This patient has experienced chronic constipation since she was a
      neonate, but anorectal manometry showed a normal anorectal reflex. Chronic
      constipation in this patient was likely to be a consequence of a mild intestinal
      disorder owing to the SOX10 mutation, and this patient was considered to have a
      clinical phenotype intermediate between type II and type IV of the syndrome.
      Chronic constipation may be recognized as indicative of a SOX10 mutation in
      patients with Waardenburg syndrome. 

PMID- 24582979
TI  - APeg3: regulation of Peg3 through an evolutionarily conserved ncRNA.
AB  - Mammalian APeg3 is an antisense gene that is localized within the 3'-untranslated
      region of the imprinted gene, Peg3. APeg3 is expressed only in the
      vasopressinergic neurons of the hypothalamus, thus is predicted to play
      significant roles in this specific area of the brain. In the current study, we
      investigate the functions of APeg3 with comparative genomics and cell line-based
      functional approaches. The transcribed region of APeg3 displays high levels of
      sequence conservation among placental mammals, but without any obvious open
      reading frame, suggesting that APeg3 may have been selected as a ncRNA gene
      during eutherian evolution. This has been further supported by the detection of a
      conserved local RNA secondary structure within APeg3. RNA secondary structure
      analyses indicate a single conserved hairpin-loop structure towards the 5' end of
      the transcript. The results from cell line-based transfection experiments
      demonstrate that APeg3 has the potential to down-regulate the transcription and
      protein levels of Peg3. The observed down-regulation by APeg3 is also somewhat
      orientation-independent. Overall, these results suggest that APeg3 has evolved as
      a ncRNA gene and controls the function of its sense gene Peg3 within specific
      neuronal cells. 

PMID- 24582968
TI  - Targeting the mevalonate cascade as a new therapeutic approach in heart disease,
      cancer and pulmonary disease.
AB  - The cholesterol biosynthesis pathway, also known as the mevalonate (MVA) pathway,
      is an essential cellular pathway that is involved in diverse cell functions. The
      enzyme 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase (HMGCR) is the
      rate-limiting step in cholesterol biosynthesis and catalyzes the conversion of
      HMG-CoA to MVA. Given its role in cholesterol and isoprenoid biosynthesis, the
      regulation of HMGCR has been intensely investigated. Because all cells require a
      steady supply of MVA, both the sterol (i.e. cholesterol) and non-sterol (i.e.
      isoprenoid) products of MVA metabolism exert coordinated feedback regulation on
      HMGCR through different mechanisms. The proper functioning of HMGCR as the
      proximal enzyme in the MVA pathway is essential under both normal physiologic
      conditions and in many diseases given its role in cell cycle pathways and cell
      proliferation, cholesterol biosynthesis and metabolism, cell cytoskeletal
      dynamics and stability, cell membrane structure and fluidity, mitochondrial
      function, proliferation, and cell fate. The blockbuster statin drugs ('statins')
      directly bind to and inhibit HMGCR, and their use for the past thirty years has
      revolutionized the treatment of hypercholesterolemia and cardiovascular diseases,
      in particular coronary heart disease. Initially thought to exert their effects
      through cholesterol reduction, recent evidence indicates that statins also have
      pleiotropic immunomodulatory properties independent of cholesterol lowering. In
      this review we will focus on the therapeutic applications and mechanisms involved
      in the MVA cascade including Rho GTPase and Rho kinase (ROCK) signaling, statin
      inhibition of HMGCR, geranylgeranyltransferase (GGTase) inhibition, and
      farnesyltransferase (FTase) inhibition in cardiovascular disease, pulmonary
      diseases (e.g. asthma and chronic obstructive pulmonary disease (COPD)), and
      cancer. 

PMID- 24582981
TI  - Discovery of novel bis-oxazolidinone compounds as potential potent and selective
      antitubercular agents.
AB  - A variety of new mono-oxazolidinone molecules by modifying the C-ring of
      Linezolid, a marketed antibiotic for MRSA, were synthesized and tested for their
      in vitro antibacterial activities against several Staphylococcus aureus,
      Mycobacterium smegmatis and two Gram-negative bacteria strains (Escherichia coli
      and Pseudomonas aeruginosa). Among them, compounds 4-7 displayed moderate
      antimicrobial activities. After development of a second oxazolidinone ring in the
      western part of the mono-oxazolidinone compounds 4-7 by a ring closure reaction
      with N,N'-carbonyldiimidazole (CDI), we found thus obtained bis-oxazolidinone
      compounds 22-25 possess excellently inhibitory activities against H37Rv but poor
      or no effects on other test bacteria. Among them, bis-oxazolidinone compound 22
      and 24 are the most potent two compounds with a same MIC value of 0.125MUg/mL
      against H37Rv virulent strain. Compound 22 also exhibited extremely low
      cytotoxicity on monkey kidney Vero cells with a selective index (IC50/MIC) over
      40,000, which suggested bis-oxazolidinone compound 22 is a promising lead
      compound for subsequent investigation in search of new antitubercular agents. 

PMID- 24582980
TI  - FoxD3 regulates cranial neural crest EMT via downregulation of tetraspanin18
      independent of its functions during neural crest formation.
AB  - The scaffolding protein tetraspanin18 (Tspan18) maintains epithelial cadherin-6B
      (Cad6B) to antagonize chick cranial neural crest epithelial-to-mesenchymal
      transition (EMT). For migration to take place, Tspan18 must be downregulated.
      Here, we characterize the role of the winged-helix transcription factor FoxD3 in
      the control of Tspan18 expression. Although we previously found that Tspan18 mRNA
      persists several hours past the stage it would normally be downregulated in FoxD3
      deficient neural folds, we now show that Tspan18 expression eventually declines.
      This indicates that while FoxD3 is crucial for initial downregulation of Tspan18,
      other factors subsequently impact Tspan18 expression. Remarkably, the classical
      EMT transcription factor Snail2 is not one of these factors. As in other
      vertebrates, FoxD3 is required for chick cranial neural crest specification and
      migration, however, FoxD3 has surprisingly little impact on chick cranial neural
      crest cell survival. Strikingly, Tspan18 knockdown rescues FoxD3-dependent neural
      crest migration defects, although neural crest specification is still deficient.
      This indicates that FoxD3 promotes cranial neural crest EMT by eliciting Tspan18
      downregulation separable from its Tspan18-independent activity during neural
      crest specification and survival. 

PMID- 24582982
TI  - Synthesis and antiproliferative evaluation of 13-aryl-13H-benzo[g]benzothiazolo
      [2,3-b]quinazoline-5,14-diones.
AB  - A simple synthesis of novel 13-aryl-13H-benzo[g]benzothiazolo [2,3-b]quinazoline
      5,14-dione derivatives was accomplished in excellent yields via the reaction of 2
      aminobenzothiazole, aromatic aldehydes and 2-hydroxy-1,4-naphthoquinone in the
      presence of amberlyst-15. The antiproliferative activities of all the synthesized
      compounds were assessed on two different human cancer cell lines (HepG2 and
      Hela), and the results showed that most of the new compounds showed good to
      potent cytotoxic activities. 

PMID- 24582983
TI  - 4,5-Dihydro-1H-pyrazolo[3,4-d]pyrimidine containing phenothiazines as
      antitubercular agents.
AB  - A series of novel dihydropyrazolo[3,4-d]pyrimidine derivatives bearing a
      phenothiazine nucleus were synthesized in excellent yields via a modified
      Biginelli multicomponent reaction. The newly synthesized compounds were
      characterized by IR, (1)H NMR, (13)C NMR, Mass spectra and elemental analysis
      followed by antimycobacterial screening. Among all the screened compounds,
      compound 4g showed most pronounced activity against Mycobacterium tuberculosis
      (Mtb) with minimum inhibitory concentration (MIC) of 0.02MUg/mL, making it more
      potent than first line antitubercular drug isoniazid. 

PMID- 24582984
TI  - Activity of caffeic acid derivatives against Candida albicans biofilm.
AB  - The aim of this study was to evaluate the caffeic acid (1) and ester derivatives
      (2-10) against Candida albicans biofilm and to investigate whether these
      compounds are able to inhibit the biofilm formation or destroy pre-formed
      biofilm. Caffeic acid ester 7, cinnamic acid ester 8 and 3,4-dihydroxybenzoic
      acid ester 10 are more active than fluconazole, used as reference drug, both on
      biofilm in formation with MIC50 values of 32, 32 and 16MUg/mL, respectively, and
      in the early stage of biofilm formation (4h) with MIC50 values of 64, 32 and
      64MUg/mL, respectively. These esters result also more active than fluconazole on
      mature biofilm (24h), especially 8 and 10 with MIC50 values of 64MUg/mL. 

PMID- 24582985
TI  - 5-Hydroxy-2-(2-phenylethyl)chromone (5-HPEC): a novel non-nitrogenous ligand for
      5-HT2B receptor.
AB  - Chromones are a class of natural products found in almost every known terrestrial
      plant with over 4000 naturally occurring derivatives having been isolated and
      structurally elucidated. Recently, 5-hydroxy-2-(2-phenylethyl)chromone (5-HPEC),
      isolated from Imperata cylindrical, showed neuroprotective activity against
      glutamate induced excitotoxicity in primary cultures of rat cortical cells. In
      comparison to other naturally occurring neuroprotective chromones, 5-HPEC
      contains fewer hydroxyl groups. Here we report our most recent characterization
      on this interesting natural product against a number of CNS receptors for the
      purpose to identify the potential molecular targets that may be related to its
      biological activity. Based on our studies, including radiobinding assays, calcium
      flux functional assays and molecular modeling studies, 5-HPEC may represent a
      type of novel nonnitrogenous ligands to the 5-HT2B receptor. 

PMID- 24582986
TI  - Fragment-based discovery of potent inhibitors of the anti-apoptotic MCL-1
      protein.
AB  - Apoptosis is regulated by the BCL-2 family of proteins, which is comprised of
      both pro-death and pro-survival members. Evasion of apoptosis is a hallmark of
      malignant cells. One way in which cancer cells achieve this evasion is thru
      overexpression of the pro-survival members of the BCL-2 family. Overexpression of
      MCL-1, a pro-survival protein, has been shown to be a resistance factor for
      Navitoclax, a potent inhibitor of BCL-2 and BCL-XL. Here we describe the use of
      fragment screening methods and structural biology to drive the discovery of novel
      MCL-1 inhibitors from two distinct structural classes. Specifically, cores
      derived from a biphenyl sulfonamide and salicylic acid were uncovered in an NMR
      based fragment screen and elaborated using high throughput analog synthesis. This
      culminated in the discovery of selective and potent inhibitors of MCL-1 that may
      serve as promising leads for medicinal chemistry optimization efforts. 

PMID- 24582987
TI  - The discovery of reverse tricyclic pyridone JAK2 inhibitors. Part 2: lead
      optimization.
AB  - This communication discusses the discovery of novel reverse tricyclic pyridones
      as inhibitors of Janus kinase 2 (JAK2). By using a kinase cross screening
      approach coupled with molecular modeling, a unique inhibitor-water interaction
      was discovered to impart excellent broad kinase selectivity. Improvements in
      intrinsic potency were achieved by utilizing a rapid library approach, while
      targeted structural changes to lower lipophilicity led to improved rat
      pharmacokinetics. This multi-pronged approach led to the identification of 31,
      which demonstrated encouraging rat pharmacokinetics, in vivo potency, and
      excellent off-target kinase selectivity. 

PMID- 24582988
TI  - Preoperative imaging in patients undergoing trachelectomy for cervical cancer:
      validation of a combined T2- and diffusion-weighted endovaginal MRI technique at
      3.0 T.
AB  - AIM: The aim of this study is to validate high-resolution endovaginal T2- and
      diffusion-weighted MRI measurements (tumour size, volume and length of uninvolved
      cervical canal) against histology in patients undergoing trachelectomy.
      PATIENTS/INTERVENTIONS: 55 consecutive patients 25-44 years with cervical cancer
      being considered for trachelectomy were prospectively assessed with endovaginal
      T2-W and diffusion-weighted MRI. Two independent observers blinded to histology
      recorded maximum tumour dimension, volume and distance from the superior aspect
      of the tumour to the internal os. Following trachelectomy, pathologist-outlined
      tumour sections were photographed with a set scale and similar measurements were
      recorded. RESULTS: Fifteen of 45 patients subsequently treated with fertility
      sparing surgery had residual tumour (median histological volume: 0.28 cm(3),
      IQR=0.14-1.06 cm(3)). Sensitivity, specificity, positive and negative predictive
      values for detecting tumour: Observer 1: 86.7%, 80.0%, 68.4%, and 92.3%,
      respectively; Observer 2: 86.7%, 90.0%, 81.0%, and 93.1%, respectively. Size and
      volume correlated between observers (r=0.96, 0.84, respectively, p<0.0001). Size
      correlated between each observer and histology (observer 1 r=0.91, p<0.0001;
      observer 2 r=0.93, p<0.0001), volume did not (observer 1: r=0.08, p=0.6; observer
      2: r=0.21, p=0.16); however, differences between observer measurements and
      histology were not significant (size p=0.09, volume p=0.15). Differences between
      MRI and histology estimates of endocervical canal length were not significant
      (p=0.1 both observers). CONCLUSION: In subcentimetre cervical cancers,
      endovaginal MRI correlates with pathology and is invaluable in assessing patients
      for fertility-sparing surgery.

PMID- 24582989
TI  - The effect of anesthesia choice on post-operative outcomes in women undergoing
      exploratory laparotomy for a suspected gynecologic malignancy.
AB  - OBJECTIVE: To determine how anesthesia choice in women undergoing laparotomy for
      gynecologic malignancy affects pain control and narcotic use. METHODS: This is a
      retrospective study of women who underwent laparotomy for suspected gynecologic
      malignancy from May 2012 to January 2013. Patients were categorized into one of
      three groups: 1) patient controlled analgesia (PCA); 2) PCA+transversus abdominis
      plane block (TAP); and 3) patient-controlled epidural analgesia (PCEA). Mean
      narcotic use and patient reported pain scores were compared. RESULTS: The
      analysis includes 112 women (44 PCA, 30 TAP, 38 PCEA). Intraoperative factors
      were not different between groups with the exception of a significant difference
      in the rate of intra-operative complications (p=0.020), with lower rates in the
      PCEA group. The groups differed in intravenous narcotic use in each of the first
      three postoperative days (day 0: p=0.014; day 1: p<0.0001; day 2: p=0.048), with
      patients in the TAP group using the least on day 0 and those in the PCEA group
      using less on postoperative days 1 and 2. In addition, the PCEA group reported
      lower pain scores on postoperative days 1 and 2 (day 1: p=0.046; day 2: p=0.008).
      CONCLUSIONS: The use of patient controlled epidural anesthesia after laparotomy
      for gynecologic malignancy is associated with decreased IV and PO narcotic use
      and improved pain control without increasing complications or length of hospital
      stay. Further investigation with prospective randomized trials is warranted to
      elucidate the optimal post-operative pain management technique.

PMID- 24582990
TI  - Functional conservation of suppressors of cytokine signaling proteins between
      teleosts and mammals: Atlantic salmon SOCS1 binds to JAK/STAT family members and
      suppresses type I and II IFN signaling.
AB  - Suppressor of cytokine signaling (SOCS) proteins are crucially involved in the
      control of inflammatory responses through their impact on various signaling
      pathways including the JAK/STAT pathway. Although all SOCS protein family members
      are identified in teleost fish, their functional properties in non-mammalian
      vertebrates have not been extensively studied. To gain further insight into SOCS
      functions in bony fish, we have identified and characterized the Atlantic salmon
      (Salmo salar) SOCS1, SOCS2 and CISH genes. These genes exhibited sequence
      conservation with their mammalian counterparts and they were ubiquitously
      expressed. SOCS1 in mammalian species has been recognized as a key negative
      regulator of interferon (IFN) signaling and recent data for the two model fish
      Tetraodon (Tetraodon nigroviridis) and zebrafish (Danio rerio) suggest that these
      functions are conserved from teleost to mammals. In agreement with this we here
      demonstrate a strong negative regulatory activity of salmon SOCS1 on type I and
      type II IFN signaling, while SOCS2a and b and CISH only moderately affected IFN
      responses. SOCS1 also inhibited IFNgamma-induced nuclear localization of STAT1
      and a direct interaction between SOCS1 and STAT1 and between SOCS1 and the Tyk2
      kinase was found. Using SOCS1 mutants lacking either the KIR domain or the ESS,
      SH2 and SOCS box domains showed that all domains affected the ability of SOCS1 to
      inhibit IFN-mediated signaling. These results are the first to demonstrate that
      SOCS1 is a potent inhibitor of IFN-mediated JAK-STAT signaling in teleost fish. 

PMID- 24582991
TI  - Pseudocystic foveal cavitation in tamoxifen retinopathy.
AB  - PURPOSE: To present 3 cases of tamoxifen-induced foveal cavitation and review
      previous prospective and cross-sectional studies. DESIGN: Observational case
      series. METHODS: Retrospective analysis of patients presenting to a single
      institution with evidence of tamoxifen-induced maculopathy. RESULTS: Three
      patients presented with pseudocystic foveal cavitation similar in appearance to
      macular telangiectasia type 2 on spectral-domain optical coherence tomography (SD
      OCT) imaging. CONCLUSIONS: Tamoxifen maculopathy is characterized by cavitation
      in the central macula with or without typical cystoid macular edema. Pathogenesis
      involves toxicity to retinal Muller cells. It can occur with low daily and
      cumulative doses of the drug, and in the absence of subjective visual complaints
      or crystalline retinopathy. Prospective research with SD OCT imaging will be
      required to gain a more accurate estimate of the incidence of tamoxifen
      retinopathy.

PMID- 24582992
TI  - Reduced risk of compressive optic neuropathy using orbital radiotherapy in
      patients with active thyroid eye disease.
AB  - PURPOSE: To compare the risk of developing compressive optic neuropathy in
      patients with active thyroid eye disease (TED) treated with corticosteroids with
      or without orbital radiotherapy. DESIGN: Retrospective single-center case-control
      study. METHODS: The clinical charts of 351 patients with active TED who received
      corticosteroids with or without orbital radiotherapy between 1999 and 2010 were
      reviewed. Patients with compressive optic neuropathy at the time of presentation
      were excluded. Group 1 received corticosteroids only and Group 2 received
      corticosteroids as well as orbital radiotherapy. The primary outcome measure was
      the development of compressive optic neuropathy. Secondary outcome measures were
      changes in other parameters indicating the activity of TED, including soft tissue
      inflammation, diplopia, ocular motility restriction, and appearance. RESULTS:
      There were 144 cases in Group 1 and 105 in Group 2. Both groups were matched for
      age, sex, and stability of thyroid function. The 2 groups differed only in the
      modality of treatment for active TED. The main indication for treatment in both
      groups was soft tissue inflammation. Corticosteroids were initiated an average of
      2.6 months following symptom onset in Group 1 and 2.5 months in Group 2. Group 2
      received orbital radiotherapy on average 4.2 months following the initiation of
      corticosteroid therapy and 8% (9/105) were intolerant to corticosteroids. At an
      average of 3.2 years follow-up, compressive optic neuropathy had developed in 17%
      (25/144) of Group 1 and 0% of Group 2 (P < .0001), on average 5.5 months
      following the initiation of corticosteroid therapy. Although both groups
      experienced a significant reduction in periocular inflammation, the radiotherapy
      treated group demonstrated a significantly greater improvement in ocular
      motility. CONCLUSION: The rate of compressive optic neuropathy was significantly
      lower and improvement in ocular motility greater in patients receiving orbital
      radiotherapy in addition to corticosteroids. Patients with active TED appear to
      have an effective and sustained response to orbital radiotherapy combined with
      corticosteroids that is protective against disease progression and the
      development of compressive optic neuropathy.

PMID- 24582993
TI  - Comparison of a donor insertion device to sheets glide in Descemet stripping
      endothelial keratoplasty: 3-year outcomes.
AB  - PURPOSE: To compare 3-year endothelial cell loss and graft survival following
      Descemet stripping automated endothelial keratoplasty (DSAEK) using the EndoGlide
      (AngioTech, Reading, Pennsylvania, USA/Network Medical Products, North Yorkshire,
      UK) donor insertion device compared to donor insertion using the Sheets glide
      technique. DESIGN: Retrospective comparative case series. METHODS: Study involved
      consecutive patients who underwent DSAEK with Fuchs endothelial dystrophy or
      pseudophakic bullous keratopathy at a single tertiary center. Clinical data with
      outcomes and donor and recipient characteristics were obtained from our ongoing
      prospective cohort from the Singapore Corneal Transplant Study. Main outcome
      measures were percent endothelial cell loss and graft survival up to 3 years.
      RESULTS: Overall percent endothelial cell loss was significantly lower in the
      EndoGlide group (100 eyes) compared to the Sheets glide group (119 eyes) at 1
      year (16.3% +/- 16.6% vs 29.5% +/- 22.2%, P < .001), 2 years (23.8% +/- 17.8% vs
      35.7% +/- 22.9%, P = .001), and 3 years (29.7% +/- 20.9% vs 38.5% +/- 24.1%, P =
      .015) postoperatively. Overall graft survival was greater in the EndoGlide
      compared to Sheets glide group up to 3 years postoperatively (97.9% vs 86.5%, log
      rank P value = .005). In eyes with Fuchs endothelial dystrophy, endothelial cell
      loss was significantly lower in the EndoGlide group (3-year: 28.2% +/- 17.9% vs
      43.4% +/- 27.1%, P = .032). In eyes with pseudophakic bullous keratopathy, the
      EndoGlide group had a superior graft survival compared to Sheets glide (log-rank
      P = .031). CONCLUSION: Endothelial cell loss was lower using a donor insertion
      device during DSAEK, compared to using the Sheets glide technique for DSAEK, in
      Asian eyes with Fuchs endothelial dystrophy, and resulted in better graft
      survival in eyes with pseudophakic bullous keratopathy.

PMID- 24582994
TI  - Importance of birth weight as a risk factor for severe retinopathy of prematurity
      when gestational age is 30 or more weeks.
AB  - PURPOSE: To determine whether birth weight less than 1500 g is a relevant
      guideline indicating the need for examination for retinopathy of prematurity
      (ROP) when gestational age at birth is 30 or more completed weeks. DESIGN: A
      retrospective observational cohort study. METHODS: A total of 266 infants in a
      single institutional neonatal intensive care unit (NICU), whose gestational age
      at birth was 30 or more weeks but whose birth weight was less than 1500 g, were
      examined according to published guidelines. Infants with lethal congenital
      anomalies or major ocular abnormalities were excluded. Outcomes were
      vascularization in retinal zone III without a prior need for treatment, or ROP
      warranting treatment. RESULTS: A study outcome was reached by 212 infants. Two
      hundred and eleven (99.5%) became vascularized through zone III without needing
      treatment. Only 1 (0.5%) required treatment for ROP. The 95% confidence interval
      for the occurrence rate of ROP requiring treatment in this cohort was 0.01%
      2.60%. CONCLUSION: Our results suggest that the occurrence rates of ROP requiring
      treatment in infants with gestational age 30 or more weeks and birth weight less
      than 1500 g is very low, and could indicate the need to revise examination
      guidelines for this subgroup of infants.

PMID- 24582995
TI  - Surgical treatment of severe congenital ptosis in patients younger than two years
      of age using preserved fascia lata.
AB  - PURPOSE: To investigate the clinical outcome of a frontalis sling using preserved
      fascia lata in the treatment of vision-obscuring congenital ptosis in patients
      less than 2 years of age. DESIGN: Retrospective, interventional case series.
      METHODS: The study was conducted in an institutional setting and included 82
      patients with visual axis-obscuring congenital ptosis. All patients underwent
      frontalis sling surgery with preserved fascia lata between November 1994 and
      December 2008, and had a minimum follow-up of 6 months. Visual and surgical
      outcomes were assessed by reviewing clinical photographs and medical charts.
      Surgical outcomes were defined as good, fair, or poor, based on the postoperative
      lid level. RESULTS: The mean age at surgery was 15.3 +/- 4.8 months. After a mean
      follow-up of 54.8 +/- 41.4 months, 64 patients (78.0%) showed good or fair
      surgical outcomes. Reoperation was performed in 16 of the patients with poor or
      fair results. Amblyopia was treated postoperatively in 75 of the 82 patients
      (91.5%) and had improved in 65 patients at the last follow-up. Postoperative
      entropion was identified in 5 cases, all of which were treated successfully. No
      other significant complications occurred. CONCLUSIONS: For patients younger than
      2 years of age, preserved fascia lata may be an appropriate substitute for
      autogenous fascia lata in frontalis sling surgery. Its long-term stability may
      enable a permanent effect in a certain proportion of patients, and may not
      require secondary surgery, which is common with synthetic materials.

PMID- 24582996
TI  - Use of intraocular video endoscopic examination in the preoperative evaluation of
      keratoprosthesis surgery to assess visual potential.
AB  - PURPOSE: To determine the clinical utility of intraocular videoendoscopy
      examination for the evaluation of the retina and optic nerve in patients being
      considered for a Boston type I keratoprosthesis (KPro). DESIGN: Interventional
      case series study. METHODS: Ten patients with a history of corneal blindness
      caused by failed penetrating keratoplasty (PK) and inability to accurately assess
      visual potential were included in this study. Ophthalmologic examination, B-scan
      ultrasonography, and pars plana videoendoscopy were carried out to assess the
      retina and optic nerve before KPro. RESULTS: Posterior segment examination was
      successfully used to evaluate the retina and optic nerve of all patients with
      opaque corneas. Out of 10 patients that underwent endoscopic examination, 3 (30%)
      were considered to be adequate candidates for KPro surgery and 7 (70%) were not.
      This was based on visualized retinal disease and/or optic nerve pathology. Of the
      3 patients that underwent KPro surgery, all of them had a significant improvement
      of vision, including counting fingers to 20/100, hand motion to 20/5, and light
      perception to 20/80, as suggested by the endoscopy preoperative examination. No
      complications of the endoscopy procedure were observed. CONCLUSIONS: This report
      demonstrates the successful use of intraocular videoendoscopy to rule out threats
      to a good visual outcome for patients being considered as candidates for KPro.
      Direct visualization of the posterior segment can be part of the preoperative
      algorithm in the decision process of performing a KPro surgery in patients when
      visual potential is questionable.

PMID- 24582997
TI  - Intraoperative corneal thickness measurement by optical coherence tomography in
      keratoconic patients undergoing corneal collagen cross-linking.
AB  - PURPOSE: To assess intraoperative variation of corneal thinnest point in
      keratoconic patients undergoing riboflavin/ultraviolet type A (UV-A) cross
      linking treatment using noncontact time-domain optical pachymetry. DESIGN:
      Prospective, noncomparative interventional study. METHODS: Ten patients underwent
      epithelium-off riboflavin/UV-A corneal cross-linking at Siena University
      Hospital; corneal thickness was measured using optical coherence tomography at
      the following times: preoperatively with epithelium on; after removal of a 9-mm
      diameter disc of epithelium; immediately after instillation of 2 drops of
      riboflavin 0.1%-dextran T 500 20% solution; after repeated instillation of
      riboflavin 0.1%-dextran T 500 20% solution every 2.5 minutes, at 10, 20, and 30
      minutes of soaking time; at the end of the treatment after 30 minutes of UV-A
      exposure with the riboflavin biofilm in situ; and finally after washing the
      riboflavin biofilm. RESULTS: The most significant decrease in thinnest point
      measurement was detected meanly in the first 10 minutes of corneal soaking. In
      this interval, the minimum recommended in various studies, a mean reduction of 
      79.28 MUm (-17.61% of initial thinnest point value after removal of the
      epithelium) was recorded. No adverse events were recorded. CONCLUSIONS: The study
      demonstrates a statistically significant intraoperative reduction in corneal
      thinnest point value during epithelium-off cross-linking procedure using standard
      riboflavin 0.1%-dextran 20% solutions. Intraoperative optical pachymetry
      evaluation during cross-linking should be recommended before starting UV-A
      irradiation, and if a thickness under 380 MUm is detected, the stroma should be
      reexpanded with hypotonic dextran-free riboflavin solutions.

PMID- 24582998
TI  - Medical nutrition therapy in adults with chronic kidney disease: integrating
      evidence and consensus into practice for the generalist registered dietitian
      nutritionist.
AB  - Chronic kidney disease is classified in stages 1 to 5 by the National Kidney
      Foundation's Kidney Disease Outcomes Quality Initiative depending on the level of
      renal function by glomerular filtration rate and, more recently, using further
      categorization depending on the level of glomerular filtration rate and
      albuminuria by the Kidney Disease Improving Global Outcomes initiative.
      Registered dietitian nutritionists can be reimbursed for medical nutrition
      therapy in chronic kidney disease stages 3 to 4 for specific clients under Center
      for Medicare and Medicaid Services coverage. This predialysis medical nutrition
      therapy counseling has been shown to both potentially delay progression to stage
      5 (renal replacement therapy) and decrease first-year mortality after initiation
      of hemodialysis. The Joint Standards Task Force of the American Dietetic
      Association (now the Academy of Nutrition and Dietetics), the Renal Nutrition
      Dietetic Practice Group, and the National Kidney Foundation Council on Renal
      Nutrition collaboratively published 2009 Standards of Practice and Standards of
      Professional Performance for generalist, specialty, and advanced practice
      registered dietitian nutritionists in nephrology care. The purpose of this
      article is to provide an update on current recommendations for screening,
      diagnosis, and treatment of adults with chronic kidney disease for application in
      clinical practice for the generalist registered dietitian nutritionist using the
      evidence-based library of the Academy of Nutrition and Dietetics, published
      clinical practice guidelines (ie, National Kidney Foundation Council on Renal
      Nutrition, Renal Nutrition Dietetic Practice Group, Kidney Disease Outcomes
      Quality Initiative, and Kidney Disease Improving Global Outcomes), the Nutrition
      Care Process model, and peer-reviewed literature.

PMID- 24582999
TI  - Lesion focused stereotactic thermo-coagulation of focal cortical dysplasia IIB: a
      new approach to epilepsy surgery?
AB  - PURPOSE: Over the last few decades, preferred epilepsy surgical approaches have
      developed from standard lobectomies to individually tailored resections. Yet, it
      remains uncertain how small surgical interventions can be without compromising
      the success of the surgery. Particularly in patients with epileptogenic lesions
      identified by magnetic resonance imaging (MRI), it is unresolved whether
      resection or destruction of the lesion suffices to eliminate the epileptogenic
      zone. We present a minimally invasive surgical approach that may provide insight
      into this issue. METHODS: Two patients with pharmacoresistant epilepsy due to
      focal cortical dysplasia type IIB demonstrated by 3 Tesla MRI were treated with
      lesion-focused stereotactic radio-frequency thermo-coagulation. In both patients,
      pathognomonic epileptic discharges were recorded from the lesion via a
      stimulation device prior to coagulation. In one patient, the suspected proximity
      of the lesion to the pyramidal tract was verified by eliciting motor evoked
      potentials from the depths of the lesion. RESULTS: Following complete and near
      complete lesion destruction, seizures (several per day or per week, respectively)
      ceased in patients A and B, with no seizures for 12 months and 5 months,
      respectively, at the time of this publication. Neither patient acquired
      persistent postoperative neurological deficits. CONCLUSION: The fact that seizure
      activity stopped after destruction of small bottom-of-sulcus dysplasias implies
      that in these cases, the epileptogenic zone and the epileptogenic lesion may
      overlap. If future studies can replicate this finding, focused lesion destruction
      could be a further development of individually tailored epilepsy surgery. The
      technique described here is especially suited for high-precision surgery close to
      eloquent brain structures.

PMID- 24583000
TI  - Reply to letter on "Coal-tar-based sealcoated pavement: a major PAH source to
      urban stream sediments".

PMID- 24583001
TI  - Vaccine Technology IV: an ECI Conference held in Albufeira, Portugal from May 20
      to 24, 2012.

PMID- 24583002
TI  - The assembly conformation of rotavirus VP6 determines its protective efficacy
      against rotavirus challenge in mice.
AB  - Viral protein assemblies have shown to be superior immunogens used in commercial
      vaccines. However, little is known about the effect of protein assembly structure
      in immunogenicity and the protection conferred by a vaccine. In this work,
      rotavirus VP6, a polymorphic protein that assembles into nanotubes, icosahedra
      (dlRLP) or trimers was used to compare the immune response elicited by three
      different assemblies. VP6 is the most antigenic and abundant rotavirus structural
      protein. It has been demonstrated that antibodies against VP6 interfere with the
      replication cycle of rotavirus, making it a vaccine candidate. Groups of mice
      were immunized with either nanotubes, dlRLP or trimers and the humoral response
      (IgG and IgA titers) was measured. Immunized mice were challenged with EDIM
      rotavirus and protection against rotavirus infection, measured as viral shedding,
      was evaluated. Immunization with nanotubes resulted in the highest IgG titers,
      followed by immunization with dlRLP. While immunization with one dose of
      nanotubes was sufficient to reduce viral shedding by 70%, two doses of dlRLP or
      trimers were required to obtain a similar protection. The results show that the
      type of assembly of VP6 results in different humoral responses and protection
      efficacies against challenge with live virus. This information is important for
      the design of recombinant vaccines in general. 

PMID- 24583003
TI  - High cell density cultivations by alternating tangential flow (ATF) perfusion for
      influenza A virus production using suspension cells.
AB  - High cell densities in animal cell culture can be obtained by continuous
      perfusion of fresh culture medium across hollow fiber membranes that retain the
      cells. Careful selection of the membrane type and cut-off allows to control
      accumulation of target molecules and removal of low molecular weight compounds.
      In this report, perfusion with the scalable ATF (alternating tangential
      filtration, Refine Technology) system was evaluated for two suspension cell
      lines, the avian cell line AGE1.CR and the human cell line CAP. Both were
      cultivated in chemically defined media optimized for batch cell growth in a 1L
      stirred tank bioreactor connected to the smallest ATF unit (ATF2) and infected
      with cell line-adapted human influenza A virus (A/PR/8/34 (H1N1), typical
      diameter: 80-100 nm). At concentrations of about 25 million cells/mL three
      different membrane cut-offs (50 kDa, 0.2 MUm and 0.5 MUm) were tested and
      compared to batch cultivations performed at 5 million cells/mL. For medium and
      large cut-offs no cell-density effect could be observed with cell-specific virus
      yields of 1428-1708 virions/AGE1.CR cell (infected with moi 0.001) and 1883-4086
      virions/CAP cell (moi of 0.025) compared to 1292 virions/AGE1.CR cell and 3883
      virions/CAP cell in batch cultures. Even at a concentration of 48 million AGE1.CR
      cells/mL (cut-off: 0.2 MUm) a cell-specific yield of 1266 virions/cell was
      reached. Only for the small cut-off (50 kDa) used with AGE1.CR cells a decrease
      in cell-specific yield was measured with 518 virions/cell. Surprisingly, the
      ratio of infectious to total virions seemed to be increased in ATF compared to
      batch cultures. AGE1.CR cell-derived virus particles were present in the permeate
      (0.2 and 0.5 MUm cut-off), whereas CAP cell-derived virions were not, suggesting
      possible differences in morphology, aggregation or membrane properties of the
      virions released by the two cell lines. To our knowledge, this is the first study
      that illustrates the potential of ATF-based perfusion of chemically defined media
      across cell-retaining membranes for production of an influenza A vaccine.

PMID- 24583005
TI  - Development of a vectored vaccine against hepatitis E virus.
AB  - Hepatitis E virus is a non-enveloped ssRNA virus [1] that causes human acute
      hepatitis through primarily fecal and oral transmission [2]. Currently, no
      commercial hepatitis E (HEV) vaccine is available. In the absence of an
      appropriate cell culture system for HEV propagation, HEV pseudocapsids (ORF2
      protein) have been produced either in Escherichia coli or in insect cells and
      they have been shown to protect monkeys against virus challenge and to be
      effective in the prevention of natural HEV infection of humans. In this work, we
      propose to develop a novel candidate vaccine against hepatitis E infection using
      adeno-associated virus (AAV) as a vector expressing the gene of the truncated
      capsid protein of HEV (aa 112-aa 660). rAAV will be produced in Sf9 cells using
      the baculovirus expression vector system. For this purpose, construction of
      recombinant baculoviruses was performed and viral stocks of BacRep, BacCap for
      serotypes 2, 5 and 6 were prepared in Sf9 cells. The recombinant baculovirus
      coding for the truncated capsid protein of HEV (BacITRHEVORF2) was also
      constructed, the virus titer was equal to 5.41*10(9) PFU/mL, at the third
      passage. Transduction of HEK 293 EBNA cells with rAAV was carried out; the
      production of HEVORF2 was confirmed by Western blot. Optimization of rAAV
      production in Sf9 cells is currently ongoing.

PMID- 24583004
TI  - Improved poliovirus D-antigen yields by application of different Vero cell
      cultivation methods.
AB  - Vero cells were grown adherent to microcarriers (Cytodex 1; 3 g L(-1)) using
      animal component free media in stirred-tank type bioreactors. Different
      strategies for media refreshment, daily media replacement (semi-batch),
      continuous media replacement (perfusion) and recirculation of media, were
      compared with batch cultivation. Cell densities increased using a feed strategy
      from 1*10(6) cells mL(-1) during batch cultivation to 1.8, 2.7 and 5.0*10(6)
      cells mL(-1) during semi-batch, perfusion and recirculation, respectively. The
      effects of these different cell culture strategies on subsequent poliovirus
      production were investigated. Increased cell densities allowed up to 3 times
      higher D-antigen levels when compared with that obtained from batch-wise Vero
      cell culture. However, the cell specific D-antigen production was lower when
      cells were infected at higher cell densities. This cell density effect is in good
      agreement with observations for different cell lines and virus types. From the
      evaluated alternative culture methods, application of a semi-batch mode of
      operations allowed the highest cell specific D-antigen production. The increased
      product yields that can easily be reached using these higher cell density
      cultivation methods, showed the possibility for better use of bioreactor capacity
      for the manufacturing of polio vaccines to ultimately reduce vaccine cost per
      dose. Further, the use of animal-component-free cell- and virus culture media
      shows opportunities for modernization of human viral vaccine manufacturing.

PMID- 24583006
TI  - Generation of a universal CD4 memory T cell recall peptide effective in humans,
      mice and non-human primates.
AB  - CD4T cells play a key role in humoral immunity by providing help to B cells,
      enabling effective antibody class switching and affinity maturation. Some
      vaccines may generate a poor response due to a lack of effective MHC class II
      epitopes, resulting in ineffective helper T cell activation and recall and
      consequently poor humoral immunity. It may be beneficial to provide a CD4T cell
      helper peptide with a vaccine particularly in the case of a poorly immunogenic
      antigen. Such a T cell helper peptide must be promiscuous in its ability to bind
      a broad range of MHC class II alleles due to broad allelic variation in the human
      population. We designed a chimeric MHC class II peptide (TpD) with epitopes from
      tetanus toxoid and diphtheria toxoid, separated by an internal cathepsin cleavage
      site. TpD was capable of inducing a memory recall response in peripheral blood
      mononuclear cells from 20/20 human donors. T cells responding to TpD showed a
      central memory phenotype. Immunization of mice with a synthetic nicotine
      nanoparticle vaccine containing TpD showed that the peptide was required for
      robust antibody production and resulted in a long term CD4 memory T cell recall
      response. As a pre-clinical model two non-human primate species, rhesus macaques
      and cynomolgus monkeys, were immunized with a nicotine nanoparticle vaccine and
      evaluated for an anti-nicotine antibody response and TpD specific memory T cells.
      We found that 4/4 rhesus monkeys had both sustained antibody production and TpD
      memory T cells for the duration of the experiment (119 days). In addition 30/30
      cynomolgus monkeys dosed with nicotine vaccine nanoparticles showed dose
      dependent antibody generation and T cell recall response compared to saline
      injected controls. In summary we have developed a potent universal memory T cell
      helper peptide (TpD) that is active in vitro in human PBMCs and in vivo in mice
      and non-human primates. 

PMID- 24583007
TI  - An animal component free medium that promotes the growth of various animal cell
      lines for the production of viral vaccines.
AB  - IPT-AFM is a proprietary animal component free medium that was developed for
      rabies virus (strain LP 2061) production in Vero cells. In the present work, we
      demonstrated the versatility of this medium and its ability to sustain the growth
      of other cell lines and different virus strains. Here, three models were
      presented: Vero cells/rabies virus (strain LP 2061), MRC-5 cells/measles virus
      (strain AIK-C) and BHK-21 cells/rabies virus (strain PV-BHK21). The cell lines
      were first adapted to grow in IPT-AFM, by progressive reduction of the amount of
      serum in the culture medium. After their adaptation, BHK-21 cells grew in
      suspension by forming clumps, whereas MRC-5 cells remained adherent. Then,
      kinetics of cell growth were studied in agitated cultures for both cell lines. In
      addition, kinetics of virus replication were investigated. 

PMID- 24583008
TI  - The multifaceted von Hippel-Lindau tumour suppressor protein.
AB  - Loss of von Hippel-Lindau protein (pVHL) is known to contribute to the initiation
      and progression of tumours associated with VHL disease as well as certain
      sporadic tumours including clear cell renal cell carcinoma (ccRCC). The VHL gene
      was first identified and cloned over 20 years ago and our understanding of its
      functions and effects has significantly increased since then. The best-known
      function of pVHL is its role in promoting the degradation of hypoxia-inducible
      factor alpha subunit (HIFalpha) as part of an E3 ubiquitin ligase complex. HIF
      stabilisation and transcriptional activation are also associated with various
      epigenetic alterations, indicating a potential role for VHL loss with changes in
      the epigenome. This review will highlight current knowledge regarding pVHL as
      well as discuss potentially novel roles of pVHL and how these may impact on
      cancer progression.

PMID- 24583010
TI  - Do PFT1 and HY5 interact in regulation of sulfate assimilation by light in
      Arabidopsis?
AB  - Sulfate assimilation pathway is highly responsive to changes in environment, but
      the mechanisms of such regulation are only slowly beginning to unravel. Here we
      show evidence that PHYTOCHROME AND FLOWERING TIME 1 (PFT1) may be another
      component of the sulfate assimilation regulatory circuit. Transcriptional
      regulation by light of the key enzyme of sulfate assimilation, adenosine
      5'phosphosulfate (APS) reductase, is disturbed in pft1-2 mutants. PFT1, however,
      affects also APS reductase enzyme activity, flux through the sulfate assimilation
      pathway and accumulation of glutathione. In addition, our data suggest a possible
      interplay of PFT1 with another transcription factor, HY5, in regulation of APS
      reductase by light. 

PMID- 24583009
TI  - Hyperglycemia induces abnormal gene expression in hematopoietic stem cells and
      their progeny in diabetic neuropathy.
AB  - Diabetic peripheral neuropathy is a major chronic diabetic complication. We have
      previously shown that in type 1 diabetic streptozotocin-treated mice, insulin-
      and TNF-alpha co-expressing bone marrow-derived cells (BMDCs) induced by
      hyperglycemia travel to nerve tissues where they fuse with nerve cells, causing
      premature apoptosis and nerve dysfunction. Here we show that similar BMDCs also
      occur in type 2 diabetic high-fat diet (HFD) mice. Furthermore, we found that
      hyperglycemia induces the co-expression of insulin and TNF-alpha in c-kit(+)Sca
      1(+)lineage(-) (KSL) progenitor cells, which maintain the same expression pattern
      in the progeny, which in turn participates in the fusion with neurons when
      transferred to normoglycemic animals. 

PMID- 24583012
TI  - Identification of insulin as a novel retinoic acid receptor-related orphan
      receptor alpha target gene.
AB  - Insulin plays an important role in regulation of lipid and glucose metabolism.
      Retinoic acid receptor-related orphan receptor alpha (RORalpha) modulates
      physiopathological processes such as dyslipidemia and diabetes. In this study, we
      found overexpression of RORalpha in INS1 cells resulted in increased expression
      and secretion of insulin. Suppression of endogenous RORalpha caused a decrease of
      insulin expression. Luciferase and electrophoretic mobility shift assay (EMSA)
      assays demonstrated that RORalpha activated insulin transcription via direct
      binding to its promoter. RORalpha was also observed to regulate BETA2 expression,
      which is one of the insulin active transfactors. In vivo analyses showed that the
      insulin transcription is increased by the synthetic RORalpha agonist SR1078.
      These findings identify RORalpha as a transcriptional activator of insulin and
      suggest novel therapeutic opportunities for management of the disease. 

PMID- 24583011
TI  - Identification of the synaptic vesicle glycoprotein 2 receptor binding site in
      botulinum neurotoxin A.
AB  - Botulinum neurotoxins (BoNTs) inhibit neurotransmitter release by hydrolysing
      SNARE proteins. The most important serotype BoNT/A employs the synaptic vesicle
      glycoprotein 2 (SV2) isoforms A-C as neuronal receptors. Here, we identified
      their binding site by blocking SV2 interaction using monoclonal antibodies with
      characterised epitopes within the cell binding domain (HC). The site is located
      on the backside of the conserved ganglioside binding pocket at the interface of
      the HCC and HCN subdomains. The dimension of the binding pocket was characterised
      in detail by site directed mutagenesis allowing the development of potent
      inhibitors as well as modifying receptor binding properties. 

PMID- 24583013
TI  - The extrageniculate visual pathway generates distinct response properties in the
      higher visual areas of mice.
AB  - BACKGROUND: Visual information conveyed through the extrageniculate visual
      pathway, which runs from the retina via the superior colliculus (SC) and the
      lateral posterior nucleus (LPN) of the thalamus to the higher visual cortex,
      plays a critical role in the visual capabilities of many mammalian species.
      However, its functional role in the higher visual cortex remains unclear. Here,
      we observed visual cortical area activity in anesthetized mice to evaluate the
      role of the extrageniculate pathway on their specialized visual properties.
      RESULTS: The preferred stimulus velocities of neurons in the higher visual areas
      (lateromedial [LM], anterolateral [AL], anteromedial [AM], and rostrolateral [RL]
      areas) were measured using flavoprotein fluorescence imaging and two-photon
      calcium imaging and were higher than those in the primary visual cortex (V1).
      Further, the velocity-tuning properties of the higher visual areas were different
      from each other. The response activities in these areas decreased after V1
      ablation; however, the visual properties' differences were preserved. After SC
      destruction, these preferences for high velocities disappeared, and their tuning
      profiles became similar to that of the V1, whereas the tuning profile of the V1
      remained relatively normal. Neural tracer experiments revealed that each of these
      higher visual areas connected with specific subregions of the LPN. CONCLUSIONS:
      The preservation of visual property differences among the higher visual areas
      following V1 lesions and their loss following SC lesions indicate that pathways
      from the SC through the thalamus to higher cortical areas are sufficient to
      support these differences.

PMID- 24583014
TI  - Slow checkpoint activation kinetics as a safety device in anaphase.
AB  - Chromosome attachment to the mitotic spindle in early mitosis is guarded by an
      Aurora B kinase-dependent error correction mechanism [1, 2] and by the spindle
      assembly checkpoint (SAC), which delays cell-cycle progression in response to
      errors in chromosome attachment [3, 4]. The abrupt loss of sister chromatid
      cohesion at anaphase creates a type of chromosome attachment that in early
      mitosis would be recognized as erroneous, would elicit Aurora B-dependent
      destabilization of kinetochore-microtubule attachment, and would activate the
      checkpoint [5, 6]. However, in anaphase, none of these responses occurs, which is
      vital to ensure progression through anaphase and faithful chromosome segregation.
      The difference has been attributed to the drop in CDK1/cyclin B activity that
      accompanies anaphase and causes Aurora B translocation away from centromeres [7
      12] and to the inactivation of the checkpoint by the time of anaphase [10, 11,
      13, 14]. Here, we show that checkpoint inactivation may not be crucial because
      checkpoint activation by anaphase chromosomes is too slow to take effect on the
      timescale during which anaphase is executed. In addition, we observe that
      checkpoint activation can still occur for a considerable time after the anaphase
      promoting complex/cyclosome (APC/C) becomes active, raising the question whether
      the checkpoint is indeed completely inactivated by the time of anaphase under
      physiologic conditions.

PMID- 24583015
TI  - Dependency of the spindle assembly checkpoint on Cdk1 renders the anaphase
      transition irreversible.
AB  - Activation of anaphase-promoting complex/cyclosome (APC/C(Cdc20)) by Cdc20 is
      delayed by the spindle assembly checkpoint (SAC). When all kinetochores come
      under tension, the SAC is turned off and APC/C(Cdc20) degrades cyclin B and
      securin, which activates separase [1]. The latter then cleaves cohesin holding
      sister chromatids together [2]. Because cohesin cleavage also destroys the
      tension responsible for turning off the SAC, cells must possess a mechanism to
      prevent SAC reactivation during anaphase, which could be conferred by a
      dependence of the SAC on Cdk1 [3-5]. To test this, we analyzed mouse oocytes and
      embryos expressing nondegradable cyclin B together with a Cdk1-resistant form of
      separase. After biorientation and SAC inactivation, APC/C(Cdc20) activates
      separase but the resulting loss of (some) cohesion is accompanied by SAC
      reactivation and APC/C(Cdc20) inhibition, which aborts the process of further
      securin degradation. Cyclin B is therefore the only APC/C(Cdc20) substrate whose
      degradation at the onset of anaphase is necessary to prevent SAC reactivation.
      The mutual activation of tension sensitive SAC and Cdk1 creates a bistable system
      that ensures complete activation of separase and total downregulation of Cdk1
      when all chromosomes have bioriented. 

PMID- 24583016
TI  - A neoproterozoic transition in the marine nitrogen cycle.
AB  - The Neoproterozoic (1000-542 million years ago, Mya) was characterized by
      profound global environmental and evolutionary changes, not least of which
      included a major rise in atmospheric oxygen concentrations [1, 2], extreme
      climatic fluctuations and global-scale glaciation [3], and the emergence of
      metazoan life in the oceans [4, 5]. We present here phylogenomic (135 proteins
      and two ribosomal RNAs, SSU and LSU) and relaxed molecular clock (SSU, LSU, and
      rpoC1) analyses that identify this interval as a key transition in the marine
      nitrogen cycle. Specifically, we identify the Cryogenian (850-635 Mya) as
      heralding the first appearance of both marine planktonic unicellular nitrogen
      fixing cyanobacteria and non-nitrogen-fixing picocyanobacteria (Synechococcus and
      Prochlorococcus [6]). Our findings are consistent with the existence of open
      ocean environmental conditions earlier in the Proterozoic adverse to nitrogen
      fixers and their evolution-specifically, insufficient availability of molybdenum
      and vanadium, elements essential to the production of high-yielding nitrogenases.
      As these elements became more abundant during the Cryogenian [7, 8], both
      nitrogen-fixing cyanobacteria and planktonic picocyanobacteria diversified. The
      subsequent emergence of a strong biological pump in the ocean implied by our
      evolutionary reconstruction may help in explaining increased oxygenation of the
      Earth's surface at this time, as well as tendency for glaciation.

PMID- 24583017
TI  - TrkB-mediated protection against circadian sensitivity to noise trauma in the
      murine cochlea.
AB  - Noise-induced hearing loss (NIHL) is a debilitating sensory impairment affecting
      10%-15% of the population, caused primarily through damage to the sensory hair
      cells or to the auditory neurons. Once lost, these never regenerate [1], and no
      effective drugs are available [2, 3]. Emerging evidence points toward an
      important contribution of synaptic ribbons in the long-term coupling of the inner
      hair cell and afferent neuron synapse to maintain hearing [4]. Here we show in
      nocturnal mice that night noise overexposure triggers permanent hearing loss,
      whereas mice overexposed during the day recover to normal auditory thresholds. In
      view of this time-dependent sensitivity, we identified a self-sustained circadian
      rhythm in the isolated cochlea, as evidenced by circadian expression of clock
      genes and ample PERIOD2::LUCIFERASE oscillations, originating mainly from the
      primary auditory neurons and hair cells. The transcripts of the otoprotecting
      brain-derived neurotrophic factor (BDNF) showed higher levels in response to day
      noise versus night noise, suggesting that BDNF-mediated signaling regulates noise
      sensitivity throughout the day. Administration of a selective BDNF receptor,
      tropomyosin-related kinase type B (TrkB), in the night protected the inner hair
      cell's synaptic ribbons and subsequent full recovery of hearing thresholds after
      night noise overexposure. The TrkB agonist shifted the phase and boosted the
      amplitude of circadian rhythms in the isolated cochlea. These findings highlight
      the coupling of circadian rhythmicity and the TrkB receptor for the successful
      prevention and treatment of NIHL.

PMID- 24583018
TI  - Identification of an olfactory signal molecule that activates the central
      regulator of reproduction in goats.
AB  - Pheromone signals regulate conspecific behavior and physiology [1]. Releaser
      pheromones induce specific behavior by exerting acute effects on the neuronal
      response, whereas primer pheromones induce physiological changes with long
      lasting effects by changing the neuroendocrine status of the recipients. In
      mammals, although several types of releaser pheromones have been identified [2
      5], the identities of primer pheromones, as well as their mechanisms of action,
      remain largely unknown [6]. In sheep and goats, the seasonally anestrous
      endocrine state of females is changed to the estrous state upon exposure to male
      scents [7, 8]. This so-called "male effect" is one of the most conspicuous primer
      pheromone effects in mammals [9, 10]. In this study, we have identified an
      olfactory signal molecule that activates the central regulator of reproduction,
      the gonadotropin-releasing hormone (GnRH) pulse generator, in goats. Using gas
      chromatography-mass spectrometry to analyze male goat headspace volatiles, we
      identified several ethyl-branched aldehydes and ketones. We
      electrophysiologically demonstrated that one of these compounds, 4-ethyloctanal,
      activates the GnRH pulse generator in female goats. This is the first report of
      an olfactory molecule that has been shown to activate the central reproductive
      axis, and this discovery will provide a new direction for primer pheromone
      research. 

PMID- 24583020
TI  - Species tree estimation of North American chorus frogs (Hylidae: Pseudacris) with
      parallel tagged amplicon sequencing.
AB  - The field of phylogenetics is changing rapidly with the application of high
      throughput sequencing to non-model organisms. Cost-effective use of this
      technology for phylogenetic studies, which often include a relatively small
      portion of the genome but several taxa, requires strategies for genome
      partitioning and sequencing multiple individuals in parallel. In this study we
      estimated a multilocus phylogeny for the North American chorus frog genus
      Pseudacris using anonymous nuclear loci that were recently developed using a
      reduced representation library approach. We sequenced 27 nuclear loci and three
      mitochondrial loci for 44 individuals on 1/3 of an Illumina MiSeq run, obtaining
      96.5% of the targeted amplicons at less than 20% of the cost of traditional
      Sanger sequencing. We found heterogeneity among gene trees, although four major
      clades (Trilling Frog, Fat Frog, crucifer, and West Coast) were consistently
      supported, and we resolved the relationships among these clades for the first
      time with strong support. We also found discordance between the mitochondrial and
      nuclear datasets that we attribute to mitochondrial introgression and a possible
      selective sweep. Bayesian concordance analysis in BUCKy and species tree analysis
      in (*)BEAST produced largely similar topologies, although we identify taxa that
      require additional investigation in order to clarify taxonomic and geographic
      range boundaries. Overall, we demonstrate the utility of a reduced representation
      library approach for marker development and parallel tagged sequencing on an
      Illumina MiSeq for phylogenetic studies of non-model organisms. 

PMID- 24583019
TI  - Cdk1 inactivation terminates mitotic checkpoint surveillance and stabilizes
      kinetochore attachments in anaphase.
AB  - Two mechanisms safeguard the bipolar attachment of chromosomes in mitosis. A
      correction mechanism destabilizes erroneous attachments that do not generate
      tension across sister kinetochores [1]. In response to unattached kinetochores,
      the mitotic checkpoint delays anaphase onset by inhibiting the anaphase-promoting
      complex/cyclosome (APC/C(Cdc20)) [2]. Upon satisfaction of both pathways, the
      APC/C(Cdc20) elicits the degradation of securin and cyclin B [3]. This liberates
      separase triggering sister chromatid disjunction and inactivates cyclin-dependent
      kinase 1 (Cdk1) causing mitotic exit. How eukaryotic cells avoid the engagement
      of attachment monitoring mechanisms when sister chromatids split and tension is
      lost at anaphase is poorly understood [4]. Here we show that Cdk1 inactivation
      disables mitotic checkpoint surveillance at anaphase onset in human cells.
      Preventing cyclin B1 proteolysis at the time of sister chromatid disjunction
      destabilizes kinetochore-microtubule attachments and triggers the engagement of
      the mitotic checkpoint. As a consequence, mitotic checkpoint proteins accumulate
      at anaphase kinetochores, the APC/C(Cdc20) is inhibited, and securin
      reaccumulates. Conversely, acute pharmacological inhibition of Cdk1 abrogates the
      engagement and maintenance of the mitotic checkpoint upon microtubule
      depolymerization. We propose that the simultaneous destruction of securin and
      cyclin B elicited by the APC/C(Cdc20) couples chromosome segregation to the
      dissolution of attachment monitoring mechanisms during mitotic exit. 

PMID- 24583021
TI  - Phylogenetics and diversification of tanagers (Passeriformes: Thraupidae), the
      largest radiation of Neotropical songbirds.
AB  - Thraupidae is the second largest family of birds and represents about 4% of all
      avian species and 12% of the Neotropical avifauna. Species in this family display
      a wide range of plumage colors and patterns, foraging behaviors, vocalizations,
      ecotypes, and habitat preferences. The lack of a complete phylogeny for tanagers
      has hindered the study of this evolutionary diversity. Here, we present a
      comprehensive, species-level phylogeny for tanagers using six molecular markers.
      Our analyses identified 13 major clades of tanagers that we designate as
      subfamilies. In addition, two species are recognized as distinct branches on the
      tanager tree. Our topologies disagree in many places with previous estimates of
      relationships within tanagers, and many long-recognized genera are not
      monophyletic in our analyses. Our trees identify several cases of convergent
      evolution in plumage ornaments and bill morphology, and two cases of social
      mimicry. The phylogeny produced by this study provides a robust framework for
      studying macroevolutionary patterns and character evolution. We use our new
      phylogeny to study diversification processes, and find that tanagers show a
      background model of exponentially declining diversification rates. Thus, the
      evolution of tanagers began with an initial burst of diversification followed by
      a rate slowdown. In addition to this background model, two later, clade-specific
      rate shifts are supported, one increase for Darwin's finches and another increase
      for some species of Sporophila. The rate of diversification within these two
      groups is exceptional, even when compared to the overall rapid rate of
      diversification found within tanagers. This study provides the first robust
      assessment of diversification rates for the Darwin's finches in the context of
      the larger group within which they evolved. 

PMID- 24583024
TI  - Prognostic importance of self-reported traits/problems/strengths and
      environmental barriers/facilitators for predicting participation outcomes in
      persons with traumatic brain injury: a systematic review.
AB  - OBJECTIVE: To conduct a systematic review of the prognostic value of self
      reported traits/problems/strengths and environmental barriers/facilitators for
      participation outcomes in persons with traumatic brain injury (TBI). DATA
      SOURCES: Articles published through August 15, 2013, obtained by conducting
      electronic searches of PubMed, PsycINFO, and Cumulative Index to Nursing and
      Allied Health Literature databases and a review of reference lists of reviewed
      articles. STUDY SELECTION: Reviewed articles were written in English and
      presented findings on adult humans with TBI, participation outcomes, and >= 1
      self-reported trait/problem/strength (eg, depression, pain, coping style) and/or
      >= 1 environment barrier/facilitator (eg, social support, family functioning,
      access to services). DATA EXTRACTION: Each of the 996 abstracts was examined by 2
      reviewers, and those failing to meet all inclusion criteria were excluded. Data
      were extracted from the 63 retained articles by 2 independent reviewers, who met
      to resolve any differences in study quality rating or evidence recorded. Study
      quality was determined using American Academy of Neurology (AAN) criteria. DATA
      SYNTHESIS: Conclusions regarding prognostic importance of self-report and
      environmental barrier/facilitator variables were made using AAN criteria.
      Conclusions regarding barrier/facilitator variables indicated that access to
      transportation, access to services, and participation in social interaction were
      possibly predictive of employment outcome, whereas living arrangements and social
      support were possibly not predictive of employment outcome. Conclusions regarding
      self-report variables indicated that the number of postconcussive symptoms,
      fatigue, and physical competence were probably predictive of employment and need
      for supervision, whereas self-efficacy was probably not predictive of employment.
      Subjective well-being, pain, and social interaction were possibly predictive of
      employment, whereas coping style was possibly not predictive. CONCLUSIONS:
      Although additional investigation is needed, self-report variables are likely to
      make important contributions to predicting participation outcomes. Future
      research should be guided by coherent conceptual models and use a consistent set
      of assessment instruments to facilitate comparisons between studies.

PMID- 24583023
TI  - Novel primate miRNAs coevolved with ancient target genes in germinal zone
      specific expression patterns.
AB  - Major nonprimate-primate differences in cortico-genesis include the dimensions,
      precursor lineages, and developmental timing of the germinal zones (GZs).
      microRNAs (miRNAs) of laser-dissected GZ compartments and cortical plate (CP)
      from embryonic E80 macaque visual cortex were deep sequenced. The CP and the GZ
      including ventricular zone (VZ) and outer and inner subcompartments of the outer
      subventricular zone (OSVZ) in area 17 displayed unique miRNA profiles. miRNAs
      present in primate, but absent in rodent, contributed disproportionately to the
      differential expression between GZ subregions. Prominent among the validated
      targets of these miRNAs were cell-cycle and neurogenesis regulators. Coevolution
      between the emergent miRNAs and their targets suggested that novel miRNAs became
      integrated into ancient gene circuitry to exert additional control over
      proliferation. We conclude that multiple cell-cycle regulatory events contribute
      to the emergence of primate-specific cortical features, including the OSVZ,
      generated enlarged supragranular layers, largely responsible for the increased
      primate cortex computational abilities.

PMID- 24583022
TI  - Delta opioid receptors presynaptically regulate cutaneous mechanosensory neuron
      input to the spinal cord dorsal horn.
AB  - Cutaneous mechanosensory neurons detect mechanical stimuli that generate touch
      and pain sensation. Although opioids are generally associated only with the
      control of pain, here we report that the opioid system in fact broadly regulates
      cutaneous mechanosensation, including touch. This function is predominantly
      subserved by the delta opioid receptor (DOR), which is expressed by myelinated
      mechanoreceptors that form Meissner corpuscles, Merkel cell-neurite complexes,
      and circumferential hair follicle endings. These afferents also include a small
      population of CGRP-expressing myelinated nociceptors that we now identify as the
      somatosensory neurons that coexpress mu and delta opioid receptors. We further
      demonstrate that DOR activation at the central terminals of myelinated
      mechanoreceptors depresses synaptic input to the spinal dorsal horn, via the
      inhibition of voltage-gated calcium channels. Collectively our results uncover a
      molecular mechanism by which opioids modulate cutaneous mechanosensation and
      provide a rationale for targeting DOR to alleviate injury-induced mechanical
      hypersensitivity. 

PMID- 24583025
TI  - Effects of ovarian hormone treatment on the gene expression of muscarinic
      acetylcholine receptors in the ovariectomized rat myometrium.
AB  - We investigate the effects of ovarian hormone on the gene expression of
      muscarinic acetylcholine receptors (M1-M5) in the myometrium using real-time PCR
      and evaluate the relationships between their expression and that of ovarian
      hormone receptors (ERalpha, ERbeta, and PgR). Wistar rats were sham operated (SO)
      or ovariectomized (OVX) and treated with vehicle, estradiol (E2), progesterone
      (P4), or both E2 and P4 for 2 days beginning on postoperative day 33. M1 and M4
      mRNA expressions were not detected in the myometrium. M2 mRNA expression did not
      change significantly in the OVX and OVX+P4 groups compared to the SO group, but
      increased significantly in the OVX+E2 group and was normalized in the OVX+E2P4
      group. M3 mRNA expression increased significantly in the OVX and OVX+P4 groups
      compared to the SO group, but was normalized in the OVX+E2 and OVX+E2P4 groups.
      M5 mRNA expression did not change significantly in all experimental groups.
      ERalpha mRNA expression increased significantly in the OVX, OVX+E2, and OVX+P4
      groups compared to the SO group, but was normalized in the OVX+E2P4 group. The
      changes in ERbeta mRNA expression were similar to those of M3 mRNA expression in
      all experimental groups. In contrast, the changes in PgR mRNA expression did not
      correspond with that of M2, M3, or M5 mRNA expression in any of the experimental
      groups. Additionally, we evaluated the relationship between the expression of
      muscarinic acetylcholine receptors and ovarian hormone receptors in estrus cycle.
      M2 mRNA expression increased significantly in diestus and metaestrus compared in
      proestrus and estrus. M3 mRNA expression increased significantly in only diestrus
      compared in the other stages. In contrast, M5 mRNA expression did not change in
      estrus cycle. The changes in ERalpha mRNA expression appeared to be similar to
      those of M2 in estrus cycle, but no significant difference was found. The changes
      in ERbeta mRNA expression were similar to those of M3 mRNA expression. The change
      in PgR mRNA expression increased significantly in diestrus compared in
      metaestrus, but did not correspond with that of M2, M3, or M5 mRNA expression in
      estrus cycle. When acetylcholine sensitivity in the myometrium was compared
      between diestrus and estrus, the sensitivity is significantly lower in estrus
      than in diestrus. These results suggest that ovarian hormones influence the
      expression of M2 and M3 in the myometrium by regulating the expression of hormone
      receptors. E2 may upregulate M2 via ERalpha, but P4 may downregulate M2 by
      inhibiting ERalpha via PgR. E2 may downregulate M3 by inhibiting ERbeta, but P4
      may not regulate the expression of M3 and ERbeta. M5 may be a constitutive
      muscarinic receptor in the myometrium because neither E2 nor P4 influence the
      expression of M5. The combination of E2 and P4 may contribute the reproduction by
      quieting down the acetylcholine-induced myometrial contraction. 

PMID- 24583026
TI  - Phytoestrogens as alternative hormone replacement therapy in menopause: What is
      real, what is unknown.
AB  - Menopause is characterized by an altered hormonal status and by a decrease in
      life quality due to the appearance of uncomfortable symptoms. Nowadays, with
      increasing life span, women spend one-third of their lifetime under menopause.
      Understanding menopause-associated pathophysiology and developing new strategies
      to improve the treatment of menopausal-associated symptoms is an important topic
      in the clinic. This review describes physiological and hormone alterations
      observed during menopause and therapeutic strategies used during this period. We
      critically address the benefits and doubts associated with estrogen/progesterone
      based hormone replacement therapy (HRT) and discuss the use of phytoestrogens
      (PEs) as a possible alternative. These relevant plant-derived compounds have
      structural similarities to estradiol, interacting with cell proteins and
      organelles, presenting several advantages and disadvantages versus traditional
      HRT in the context of menopause. However, a better assessment of PEs
      safety/efficacy would warrant a possible widespread clinical use. 

PMID- 24583028
TI  - Antiviral therapy of hepatitis C in 2014: do we need resistance testing?
AB  - The treatment of chronic hepatitis C has fundamentally changed since the approval
      of the first direct-acting antivirals (DAA) in 2011. In addition to telaprevir
      and boceprevir, in 2014 two new NS3 protease inhibitors (simeprevir and
      faldaprevir), one non-nucleoside polymerase inhibitor (sofosbuvir) and one NS5a
      replication complex inhibitor (daclatasvir) have expanded the treatment options
      for chronic hepatitis C. Resistance-associated variants (RAV) are naturally
      produced during the HCV life cycle. The frequency of RAVs within HCV quasispecies
      mainly depends on their replicational fitness. Variants conferring resistance to
      nucleos(t)ide analogues have not been detected, and the majority of NS3 protease
      resistant variants are present at low frequencies (0.1-3%) before initiation of
      DAA-based therapies. However, the Q80K variant conferring resistance to
      simeprevir has been observed in 9-48% of untreated HCV genotype 1a-infected
      patients, leading to reduced SVR rates. Resistant variants are detectable in the
      majority of patients with treatment failure to NS3 protease inhibitor- or NS5a
      inhibitor-based antiviral therapy. Long-term follow-up studies by population
      based sequence analysis have shown the disappearance of resistant variants in the
      majority of patients, with median times to loss of mutations of 4-64weeks. For
      the nucleotide analogue sofosbuvir, the emergence of the S282T resistant variant
      has been observed only in single patients, with reversion to wild-type within
      several weeks. Data are sparse on retreatment of patients with the same DAA or
      the same class of DAAs. However, retreatment with a different class of DAAs after
      failure of NS3 protease inhibitor-based therapy has been successful in small
      studies. This article forms part of a symposium in Antiviral Research on
      "Hepatitis C: next steps toward global eradication." 

PMID- 24583029
TI  - Inhibition of replication of porcine reproductive and respiratory syndrome virus
      by hemin is highly dependent on heme oxygenase-1, but independent of iron in MARC
      145 cells.
AB  - Current vaccines against porcine reproductive and respiratory syndrome virus
      (PRRSV) have failed to provide sustainable disease control, and development of
      new antiviral strategies is of great importance. The present study investigated
      the mechanism of the antiviral effect of hemin during PRRSV infection in MARC-145
      cells. Hemin, a commercial preparation of heme, is used as an iron donor or heme
      oxygenase 1 (HO-1) inducer, and has been shown to provide antiviral activity in
      many studies. In the current study, the anti-PRRSV activity of hemin was
      identified through suppressing PRRSV propagation. The 50% inhibitory
      concentration (IC50) of hemin antiviral activity was estimated to be 32MUM, and
      the 50% cytotoxic concentration (CC50) of hemin was found to be higher than
      125MUM. Further study showed that the antiviral activity of hemin is independent
      of iron. In addition, after treatment with Protoporphyrin IX zinc (II) (ZnPP) or
      Sn (IV) Protoporphyrin IX dichloride (SnPP), inhibitors of HO-1, the inhibition
      of viral replication by hemin was partially reversed. Additionally, it was
      confirmed that hemin and N-acetyl cysteine were able to significantly reduce
      reactive oxygen species (ROS) in MARC-145 cells infected with virus. N-acetyl-L
      cysteine (NAC), however, did not produce a reduction in viral load or promote
      expression of HO-1. Taken together, these data indicate that the effect of hemin
      on the inhibition of PRRSV propagation via HO-1 induction, as well as the
      antiviral mechanism of HO-1, is not dependent on decreased levels of ROS. In
      conclusion, these data demonstrate that hemin had antiviral activity against
      PRRSV and may serve as a useful antiviral agent inhibiting PRRSV replication. 

PMID- 24583030
TI  - A murine model of coxsackievirus A16 infection for anti-viral evaluation.
AB  - Coxsackievirus A16 (CA16) is one of the main causative agents of hand, foot and
      mouth disease (HFMD), which is a common infectious disease in children. CA16
      infection may lead to severe nervous system damage and even death in humans.
      However, study of the pathogenesis of CA16 infection and development of vaccines
      and anti-viral agents are hindered partly by the lack of an appropriate small
      animal model. In the present study, we developed and characterized a murine model
      of CA16 infection. We show that neonatal mice are susceptible to CA16 infection
      via intraperitoneal inoculation. One-day-old mice infected with 2*10(6)TCID50 of
      CA16/SZ05 strain consistently exhibited clinical signs, including reduced
      mobility, and limb weakness and paralysis. About 57% of the mice died within
      14days after infection. Significant damage in the brainstem, limb muscles and
      intestines of the infected mice in the moribund state was observed by
      histological examination, and the presence of CA16 in neurons of the brainstem
      was demonstrated by immunohistochemical staining with a CA16-specific polyclonal
      antibody, strongly suggesting the involvement of the central nervous system in
      CA16 infection. Analysis of virus titers in various organs/tissues collected at
      3, 6 and 9days post-infection, showed that skeletal muscle was the major site of
      virus replication at the early stage of infection, while the virus mainly
      accumulated in the brain at the late stage. In addition, susceptibility of mice
      to CA16 infection was found to be age dependent. Moreover, different CA16 strains
      could exhibit varied virulence in vivo. Importantly, we demonstrated that post
      exposure treatment with an anti-CA16 monoclonal antibody fully protected mice
      against lethal CA16 infection. Collectively, these results indicate the
      successful development of a CA16 infection mouse model for anti-viral evaluation.

PMID- 24583027
TI  - Treatment of norovirus infections: moving antivirals from the bench to the
      bedside.
AB  - Noroviruses (NV) are the most common cause of acute gastrointestinal illness in
      the United States and worldwide. The development of specific antiviral
      countermeasures has lagged behind that of other viral pathogens, primarily
      because norovirus disease has been perceived as brief and self-limiting and
      robust assays suitable for drug discovery have been lacking. The increasing
      recognition that NV illness can be life-threatening, especially in
      immunocompromised patients who often require prolonged hospitalization and
      intensive supportive care, has stimulated new research to develop an effective
      antiviral therapy. Here, we propose a path forward for evaluating drug therapy in
      norovirus-infected immunocompromised individuals, a population at high risk for
      serious and prolonged illness. The clinical and laboratory features of norovirus
      illness in immunocompromised patients are reviewed, and potential markers of drug
      efficacy are defined. We discuss the potential design of clinical trials in these
      patients and how an antiviral therapy that proves effective in immunocompromised
      patients might also be used in the setting of acute outbreaks, especially in
      confined settings such as nursing homes, to block the spread of infection and
      reduce the severity of illness. We conclude by reviewing the current status of
      approved and experimental compounds that might be evaluated in a hospital
      setting. 

PMID- 24583031
TI  - In vitro surrogate models to aid in the development of antivirals for the
      containment of foot-and-mouth disease outbreaks.
AB  - Foot-and-mouth disease virus (FMDV) is a highly pathogenic member of the genus
      Aphthovirus (family Picornaviridae) that is only to be manipulated in high
      containment facilities, thus complicating research on and discovery of antiviral
      strategies against the virus. Bovine rhinitis B virus (BRBV) and equine rhinitis
      A virus (ERAV), phylogenetically most closely related to FMDV, were explored as
      surrogates for FMDV in antiviral studies. Although no efficient cell culture
      system has been reported so far for BRBV, we demonstrate that infection of
      primary bovine kidney cells resulted in an extensive but rather poorly
      reproducible induction of cytopathic effect (CPE). Madin-Darby bovine kidney
      cells on the other hand supported viral replication in the absence of CPE.
      Antiviral tests were developed for ERAV in Vero A cells employing a viral RNA
      reduction assay and CPE-reduction assay; the latter having a Z' factor of 0.83+/
      0.07. The BRBV and ERAV models were next used to assess the anti-aphthovirus
      activity of two broad-spectrum antiviral agents 2'-C-methylcytidine (2CMC) and
      ribavirin, as well as of the enterovirus-specific inhibitor enviroxime. The
      effects of the three compounds in the CPE-reduction (ERAV) and viral RNA
      reduction assays (BRBV and ERAV) were comparable. Akin to 2CMC, compound A, a
      recently-discovered non-nucleoside pan-serotype FMDV inhibitor, also inhibited
      the replication of both BRBV and ERAV, whereas enviroxime was devoid of activity.
      The BRBV and ERAV surrogate models reported here can be manipulated in BSL-2
      laboratories and may facilitate studies to unravel the mechanism of action of
      novel FMDV inhibitors. 

PMID- 24583032
TI  - What are the pros and cons of the use of host-targeted agents against hepatitis
      C?
AB  - Hepatitis C virus (HCV) therapy is living a revolution. Host-targeted agents
      (HTAs) block HCV production by interacting with host cell components. Because
      they target conserved host proteins, not variable viral proteins, HTAs have the
      potential for pangenotypic antiviral activity and a high barrier to resistance.
      Only two HTAs have reached clinical development, including specific inhibitors of
      cyclophilin A peptidyl-prolyl cis/trans isomerase activity and antagonists of
      microRNA-122. Cyclophilin inhibitors have proven to be relatively well tolerated
      and can be confidently used as backbones of all-oral, interferon-free regimens.
      In addition, HTAs such as cyclophilin inhibitors offer opportunities for
      "panviral" approaches when they target mechanisms common to viruses of the same
      or different families. This article forms part of a symposium in Antiviral
      Research on "Hepatitis C: next steps toward global eradication." 

PMID- 24583034
TI  - The Notch co-repressor protein NKAP is highly expressed in adult mouse
      subventricular zone neural progenitor cells.
AB  - In the adult mammalian brain niches for neural stem cells are maintained, which
      enable a steady-state neurogenesis. This process is tightly regulated by multiple
      niche factors, including Notch and NF-kappaB signaling. The NF-kappaB-activating
      protein (NKAP) has previously been shown to act as Notch co-repressor component
      by binding CIR and recruiting HDAC3 in T-cell development and furthermore to
      regulate NF-kappaB-dependent transcription. Here, we provide first evidence for
      the expression of NKAP in neurogenic cells of the adult mammalian brain. NKAP is
      highly expressed in Mash1(+) transit amplifying cells and PSA-NCAM(+) migrating
      neuroblasts throughout the subventricular zone (SVZ) and the rostral migratory
      stream (RMS), as well as in the hippocampus. We further show that NKAP expression
      levels are downregulated during the course of the RMS. Eventually, most
      differentiated cells in the olfactory bulb (OB) and the corpus callosum only
      display low levels of NKAP expression. Finally, large subsets of mature neurons
      in the OB, the hippocampus and the thalamus express NKAP at high levels,
      suggesting an additional role of NKAP outside of SVZ progenitor cells. 

PMID- 24583036
TI  - Diffusion tensor imaging of white matter degeneration in Alzheimer's disease and
      mild cognitive impairment.
AB  - Alzheimer's disease (AD) has traditionally been regarded as a disease of the gray
      matter (GM). However, the advent of diffusion tensor imaging (DTI) has
      contributed to new knowledge about how changes in white matter (WM)
      microstructure in vivo may be directly related to the pathophysiology of AD. It
      is now evident that WM is heavily affected in AD, even at early stages. Still,
      our knowledge about WM degeneration in AD is poor compared to what we know about
      GM atrophy. For instance, it has not been clear if WM can be directly affected in
      AD independently of GM degeneration, or whether WM changes mainly represent
      secondary effects of GM atrophy, e.g. through Wallerian degeneration. In this
      paper, we review recent studies using DTI to study WM alterations in AD. These
      studies suggest that microstructural WM affection at pre-AD stages cannot
      completely be accounted for by concomitant GM atrophy. Further, recent research
      has demonstrated relationships between increased cerebrospinal fluid levels of
      Tau proteins and changes in WM microstructure indexed by DTI, which could
      indicate that WM degeneration in pre-AD stages is related to ongoing axonal
      damage. We conclude that DTI is a promising biomarker for AD, with the potential
      also to identify subgroups of patients with especially high degree of WM
      affection, thereby contributing to more differentiated pre-AD diagnoses. However,
      more research and validation studies are needed before it is realistic to use
      this information in clinical practice with individual patients. 

PMID- 24583033
TI  - The past, present and future of neutralizing antibodies for hepatitis C virus.
AB  - Hepatitis C virus (HCV) is a major cause of liver disease and hepatocellular
      carcinoma worldwide. HCV establishes a chronic infection in the majority of
      cases. However, some individuals clear the virus, demonstrating a protective role
      for the host immune response. Although new all-oral drug combinations may soon
      replace traditional ribavirin-interferon therapy, the emerging drug cocktails
      will be expensive and associated with side-effects and resistance, making a
      global vaccine an urgent priority. T cells are widely accepted to play an
      essential role in clearing acute HCV infection, whereas the role antibodies play
      in resolution and disease pathogenesis is less well understood. Recent studies
      have provided an insight into viral neutralizing determinants and the protective
      role of antibodies during infection. This review provides a historical
      perspective of the role neutralizing antibodies play in HCV infection and
      discusses the therapeutic benefits of antibody-based therapies. This article
      forms part of a symposium in Antiviral Research on "Hepatitis C: next steps
      toward global eradication." 

PMID- 24583035
TI  - MU-Opioid receptor inhibition of substance P release from primary afferents
      disappears in neuropathic pain but not inflammatory pain.
AB  - Opiate analgesia in the spinal cord is impaired during neuropathic pain. We
      hypothesized that this is caused by a decrease in MU-opioid receptor inhibition
      of neurotransmitter release from primary afferents. To investigate this
      possibility, we measured substance P release in the spinal dorsal horn as
      neurokinin 1 receptor (NK1R) internalization in rats with chronic constriction
      injury (CCI) of the sciatic nerve. Noxious stimulation of the paw with CCI
      produced inconsistent NK1R internalization, suggesting that transmission of
      nociceptive signals by the injured nerve was variably impaired after CCI. This
      idea was supported by the fact that CCI produced only small changes in the
      ability of exogenous substance P to induce NK1R internalization or in the release
      of substance P evoked centrally from site of nerve injury. In subsequent
      experiments, NK1R internalization was induced in spinal cord slices by
      stimulating the dorsal root ipsilateral to CCI. We observed a complete loss of
      the inhibition of substance P release by the MU-opioid receptor agonist [D
      Ala(2), NMe-Phe(4), Gly-ol(5)]-enkephalin (DAMGO) in CCI rats but not in sham
      operated rats. In contrast, DAMGO still inhibited substance P release after
      inflammation of the hind paw with complete Freund's adjuvant and in naive rats.
      This loss of inhibition was not due to MU-opioid receptor downregulation in
      primary afferents, because their colocalization with substance P was unchanged,
      both in dorsal root ganglion neurons and primary afferent fibers in the dorsal
      horn. In conclusion, nerve injury eliminates the inhibition of substance P
      release by MU-opioid receptors, probably by hindering their signaling mechanisms.

PMID- 24583038
TI  - The suprachiasmatic nucleus is part of a neural feedback circuit adapting blood
      pressure response.
AB  - The suprachiasmatic nucleus (SCN) is typically considered our autonomous clock
      synchronizing behavior with physiological parameters such as blood pressure (BP),
      just transmitting time independent of physiology. Yet several studies show that
      the SCN is involved in the etiology of hypertension. Here, we demonstrate that
      the SCN is incorporated in a neuronal feedback circuit arising from the nucleus
      tractus solitarius (NTS), modulating cardiovascular reactivity. Tracer injections
      into the SCN of male Wistar rats revealed retrogradely filled neurons in the
      caudal NTS, where BP information is integrated. These NTS projections to the SCN
      were shown to be glutamatergic and to terminate in the ventrolateral part of the
      SCN where light information also enters. BP elevations not only induced increased
      neuronal activity as measured by c-Fos in the NTS but also in the SCN. Lesioning
      the caudal NTS prevented this activation. The increase of SCN neuronal activity
      by hypertensive stimuli suggested involvement of the SCN in counteracting BP
      elevations. Examining this possibility we observed that elevation of BP, induced
      by alpha1-agonist infusion, was more than twice the magnitude in SCN-lesioned
      animals as compared to in controls, indicating indeed an active involvement of
      the SCN in short-term BP regulation. We propose that the SCN receives BP
      information directly from the NTS enabling it to react to hemodynamic
      perturbations, suggesting the SCN to be part of a homeostatic circuit adapting BP
      response. We discuss how these findings could explain why lifestyle conditions
      violating signals of the biological clock may, in the long-term, result in
      cardiovascular disease. 

PMID- 24583037
TI  - Lixisenatide rescues spatial memory and synaptic plasticity from amyloid beta
      protein-induced impairments in rats.
AB  - Alzheimer's disease (AD) is a progressive and degenerative disorder accompanied
      by cognitive impairment, but effective strategies against AD are currently not
      available. Interestingly, glucagon-like peptide-1 (GLP-1) used in type 2 diabetes
      mellitus (T2DM) has shown neuroprotective effects in preclinical studies of AD.
      Lixisenatide, an effective GLP-1 receptor (GLP-1R) agonist with much longer half
      life than GLP-1, has been licensed in the EU as a treatment for T2DM. However,
      the neuroprotective effects of lixisenatide in the brain remain to be clarified.
      In the present study, we report for the first time the effects of lixisenatide on
      the amyloid beta (Abeta) protein-induced impairments in spatial learning and
      memory of rats, and investigated its electrophysiological and molecular
      mechanisms. We found that: (1) bilateral intrahippocampal injection of Abeta25-35
      resulted in a significant decline in spatial learning and memory of rats, as well
      as a suppression of in vivo hippocampal long-term potentiation (LTP); (2)
      lixisenatide treatment effectively prevented the Abeta25-35-induced impairments;
      (3) lixisenatide inhibited the Abeta25-35 injection-induced activation of
      glycogen synthase kinase 3beta (GSK3beta), with a significant increase in the
      phosphorylation of ser9 and a significant decrease in the phosphorylation of
      Y216. These results indicate that lixisenatide, by affecting the PI3K-Akt
      GSK3beta pathway, can prevent Abeta-related impairments in synaptic plasticity
      and spatial memory of rats, suggesting that lixisenatide may be a novel and
      effective treatment for AD.

PMID- 24583039
TI  - The relationship of prenatal ethanol exposure and anxiety-related behaviors and
      central androgen receptor and vasopressin expression in adult male mandarin
      voles.
AB  - Prenatal exposure to ethanol has been shown to increase the risk of anxiety in
      offspring. Here, we tested the effect of prenatal ethanol exposure on adult male
      mandarin voles (Microtus mandarinus). We examined anxiety-like behavior in the
      open field and elevated plus-maze tests in males exposed to ethanol prenatally.
      One control group was not exposed to ethanol or saline, while another control
      group was exposed to saline. At the age of 90days, males were tested and levels
      of serum testosterone, androgen receptor immunoreactive neurons (AR-IRs) and
      arginine vasopressin immunoreactive neurons (AVP-IRs) were measured. Animals
      exposed to ethanol spent less time in the center of the chamber, covered less
      distance and conducted fewer crossings in the open-field test. These animals also
      spent less time and conducted fewer crossings in the open arms. However, they
      spent more time and made more entries in the closed arms, and traveled less total
      distance during the elevated plus-maze test, compared to the control voles. Serum
      T was lower in the ethanol group, and the AR-IR number in the bed nucleus of the
      stria terminalis (BNST), medial preoptic area (mPOA) and medial amygdaloid
      nucleus (MeA) was significantly lower. The number of AVP-IRs in the
      paraventricular nucleus (PVN) and supraoptic nucleus (SON) of the ethanol group
      was higher than that of the control groups. Our findings suggest that prenatal
      ethanol exposure may lead to reduced serum T levels, decreased AR and increased
      AVP in the CNS and result in the development of anxiety-like behaviors. 

PMID- 24583040
TI  - The cognitive and neural time course of empathy and sympathy: an electrical
      neuroimaging study on self-other interaction.
AB  - Although extensively investigated in socio-cognitive neuroscience, empathy is
      difficult to study. The first difficulty originates in its multifaceted nature.
      According to the multidimensional model, empathy combines emotional, automatic
      (simulation), cognitive (mentalizing) and regulatory (executive functions)
      processes. Substantial functional magnetic resonance imaging (fMRI) data
      demonstrated that co-activations in the mirror neuron system (MNS) and
      mentalizing network (MENT) sustain this co-recruitment of so-called first- and
      second-person-like processes. Because of the poor temporal resolution of fMRI
      techniques, we currently lack evidence about the precise timing of the MNS-MENT
      combination. An important challenge is, thus, to disentangle how MNS and MENT
      dynamically work together along time in empathy. Moreover, the role of the
      executive functions in the MNS-MENT combination time course is still unknown.
      Second, empathy - feeling into - is closely related to sympathy - feeling with -
      and both phenomena are often conflated in experimental studies on
      intersubjectivity. In this electrical neuroimaging (EEG) pilot-study, we tested
      whether the egocentered vs. heterocentered visuo-spatial mechanisms respectively
      associated with sympathy and empathy differentially modulate the dynamic
      combination of the MNS-MENT activations in their respective neural time course.
      For that, we employed our newly developed behavioral paradigm assessing the visuo
      spatial - but not emotional - features of empathy and sympathy. Using a data
      driven approach, we report that empathy and sympathy are underlied by sequential
      activations in the MNS from the insula to the inferior frontal gyrus (IFG)
      between 63ms and 424ms. However, at 333-424ms, empathy triggered greater co
      activations in the right IFG and dorsolateral prefrontal cortex (dlPFC)
      (executive functions). Linking together our present and prior (Thirioux et al.,
      2010) findings from the same dataset, we suggest that this greater recruitment of
      the right dlPFC monitors the shift from egocentered and first-person-like
      mechanisms in the MNS to heterocentered and second-person-like mechanisms in the
      left temporo-parietal junction within the MENT, i.e., reflecting the onset of
      perspective-change processes in the neural time course of empathy. Contrasting
      with sympathy, this recruitment of the executive functions could modulate the
      output end of the mirroring processing in the premotor and sensorimotor cortices.

PMID- 24583041
TI  - A hyperexcitability phenotype in mouse trigeminal sensory neurons expressing the
      R192Q Cacna1a missense mutation of familial hemiplegic migraine type-1.
AB  - Missense mutation R192Q in the CACNA1A gene causes familial hemiplegic migraine
      type-1 (FHM1), a monogenic subtype of migraine with aura. Using knock-in (KI)
      gene targeting we introduced this mutation into the mouse gene and generated a
      transgenic mouse model to investigate basic mechanisms of migraine
      pathophysiology. While FHM1 R192Q KI trigeminal ganglia were previously shown to
      exhibit constitutive up-regulation of ATP-gated P2X3 receptors, little is known
      about the firing properties of trigeminal sensory neurons, which convey
      nociceptive inputs to higher brain centers. We patch-clamped trigeminal sensory
      neurons to search for differences in firing properties between wildtype (WT) and
      KI cells in culture. Although various subclasses of trigeminal neurons were
      observed with respect to their firing patterns evoked by intracellular current
      injection, their distribution among WT and KI cells was similar with only small
      differences in rheobase or input resistance values. However, when neurons were
      excited by either alpha,beta-methyl-ATP to stimulate P2X3 receptors or capsaicin
      to activate transient receptor potential vanilloid (TRPV1) receptors, the firing
      threshold in KI neurons was significantly lowered and followed by a larger number
      of spikes. Activation by alpha,beta-methyl-ATP was associated with a transient
      cluster of action potentials, while capsaicin elicited more persistent firing.
      Using alpha,beta-methyl-ATP or capsaicin, two functional classes of WT or KI
      neurons were distinguished according to the first spike latency, which suggests
      that a subgroup of neurons may be indirectly activated, probably via crosstalk
      between neurons and satellite glial cells. Thus, our results are consistent with
      reported facilitated trigeminal pain behavior of FHM1 R192Q KI mice. 

PMID- 24583042
TI  - The developmental disruptions of serotonin signaling may involved in autism
      during early brain development.
AB  - Autism is a developmental disorder defined by the presence of a triad of
      communication, social and stereo typical behavioral characteristics with onset
      before 3years of age. In spite of the fact that there are potential environmental
      factors for autistic behavior, the dysfunction of serotonin during early
      development of the brain could be playing a role in this prevalence rise.
      Serotonin can modulate a number of developmental events, including cell division,
      neuronal migration, cell differentiation and synaptogenesis. Hyperserotonemia
      during fetal development results in the loss of serotonin terminals through
      negative feedback. The increased serotonin causes a decrease of oxytocin in the
      paraventricular nucleus of the hypothalamus and an increase in calcitonin gene
      related peptide (CGRP) in the central nucleus of the amygdale, which are
      associated with social interactions and vital in autism. However, hyposerotonemia
      may be also relevant to the development of sensory as well as motor and cognitive
      faculties. And the paucity of placenta-derived serotonin should have potential
      importance when the pathogenesis of autism is considered. This review briefly
      summarized the developmental disruptions of serotonin signaling involved in the
      pathogenesis of autism during early development of the brain. 

PMID- 24583043
TI  - Neurodevelopmental and neurobehavioural effects of polybrominated and
      perfluorinated chemicals: a systematic review of the epidemiological literature
      using a quality assessment scheme.
AB  - Concerns over effects of halogenated persistent environmental contaminants on the
      developing brain have been expressed for many years, and human biomonitoring has
      confirmed that low-level, prenatal and/or postnatal exposure of children to these
      chemicals is ubiquitous. Over the last decade there have been increasing reports
      in the epidemiological literature of the potential association of exposure to
      polybromo diphenylethers (PBDEs) and perfluorinated chemicals (PFCs) with
      neurodevelopmental and/or neurobehavioural effects in infants and children, such
      as adverse birth outcomes, cognitive deficits, developmental delay and attention
      deficit hyperactivity disorders (ADHD). However, direct evidence from
      epidemiology studies has been limited and contradictory. Given the general lack
      of comparability across studies in terms of design, conduct, methodology and
      reporting, we developed a checklist-type quality assessment scheme based on the
      STROBE guidelines and the proposed HONEES criteria, and conducted a systematic
      review of the epidemiological peer-reviewed literature published since 2006 on
      neurodevelopmental and/or neurobehavioural effects following prenatal and
      postnatal exposure to PBDEs and PFCs. We rated 7 of the 18 studies that met our
      inclusion criteria as being of high quality, 7 of moderate quality and 4 of low
      quality. Frequently observed shortcomings were the lack of consideration of
      confounding factors; uncertainties regarding exposure characterization;
      inadequate sample size; the lack of a clear dose-response; and the
      representativeness/generalizability of the results. Collectively, the
      epidemiological evidence does currently not support a strong causal association
      between PBDEs and PFCs and adverse neurodevelopmental and neurobehavioural
      outcomes in infants and children. However, despite their limitations, the studies
      raise questions that require further investigation through hypothesis-driven
      studies using more harmonized study designs and methodologies, more detailed
      exposure assessments and repeated testing with larger study populations. 

PMID- 24583044
TI  - Organochlorine pesticides and antioxidant enzymes are inversely correlated with
      liver enzyme gene expression in Cyprinus carpio.
AB  - The present study was designed to investigate the association between levels of
      organochlorine pesticides (OCPs) and liver enzyme responses in Cyprinus carpio.
      Fish were caught at three stations in the Buyuk Menderes River (BMR): the origin,
      the Saraykoy station, and the estuary. Seventeen OCPs were quantified in liver
      tissue, as well as in river water by gas chromatography (GC)-electron capture
      detection, and structures were confirmed by negative chemical ionization-GC-mass
      spectrometry. The activities of CYP1A, GST, Se-GPx, CAT, and SODs were determined
      by spectrophotometry or fluorimetry. The mRNA levels of CYP1A, GST, and SOD1 were
      quantified by real-time RT-PCR. CYP1A and antioxidant enzyme activities were
      dramatically higher at the Saraykoy station, where OCP pollution is higher than
      the other two stations. Mn-SOD is responsible for the increase in total SOD
      activity in the Saraykoy samples. However, gene expression levels of certain
      enzymes were heavily suppressed. Our findings show that the transcriptional and
      functional responses of CYP1A and antioxidant enzymes are inversely correlated. 

PMID- 24583046
TI  - Cholesterol-loaded-cyclodextrins improve the post-thaw quality of stallion sperm.
AB  - An unacceptable proportion of stallion sperm do not survive the freeze-thaw
      process. The hypothesis of this study was that adding cholesterol to a stallion
      semen extender would stabilise the sperm membrane, resulting in an improved post
      thaw semen quality in terms of increased sperm viability, membrane integrity and
      fluidity, and reduced oxidative stress. Semen was collected from three stallions
      and diluted in four extenders: TALP; TALP+0.75mg methyl-beta-cyclodextrin
      cholesterol (MbetaCD)/mL (MbetaCD0.75); TALP+1.5mg MbetaCD-cholesterol/mL
      (MbetaCD1.5); and Equipro. Following 15min incubation, samples were centrifuged
      and diluted to 100*10(6)sperm/mL, frozen in 0.5mL straws and stored in liquid
      nitrogen. Sperm from each treatment was assessed for progressive linear motility
      (PLM) and acceptable membrane integrity under hypotonic conditions on a phase
      contrast microscope at 1000* while viability, membrane fluidity and superoxide
      generation were assessed by flow cytometry. The MbetaCD1.5 and MbetaCD0.75
      treatments had a greater proportion of viable sperm than the TALP treatment
      (P<0.01). There was no effect of treatment on PLM or membrane integrity. The
      MbetaCD1.5 treatment had a greater proportion of viable sperm positive for
      membrane fluidity than the TALP treatment (P<0.05). The MbetaCD1.5 and
      MbetaCD0.75 treatments had a lesser proportion of viable sperm positive for
      superoxide generation than the TALP treatment (P<0.001). This study has
      demonstrated that adding cholesterol to stallion sperm prior to cryopreservation
      increases post-thaw viability, with these viable sperm being of better quality in
      terms of increased membrane fluidity and reduced superoxide generation. 

PMID- 24583045
TI  - Are three methods better than one? A comparative assessment of usability
      evaluation methods in an EHR.
AB  - OBJECTIVE: To comparatively evaluate the effectiveness of three different methods
      involving end-users for detecting usability problems in an EHR: user testing,
      semi-structured interviews and surveys. MATERIALS AND METHODS: Data were
      collected at two major urban dental schools from faculty, residents and dental
      students to assess the usability of a dental EHR for developing a treatment plan.
      These included user testing (N=32), semi-structured interviews (N=36), and
      surveys (N=35). RESULTS: The three methods together identified a total of 187
      usability violations: 54% via user testing, 28% via the semi-structured interview
      and 18% from the survey method, with modest overlap. These usability problems
      were classified into 24 problem themes in 3 broad categories. User testing
      covered the broadest range of themes (83%), followed by the interview (63%) and
      survey (29%) methods. DISCUSSION: Multiple evaluation methods provide a
      comprehensive approach to identifying EHR usability challenges and specific
      problems. The three methods were found to be complementary, and thus each can
      provide unique insights for software enhancement. Interview and survey methods
      were found not to be sufficient by themselves, but when used in conjunction with
      the user testing method, they provided a comprehensive evaluation of the EHR.
      CONCLUSION: We recommend using a multi-method approach when testing the usability
      of health information technology because it provides a more comprehensive picture
      of usability challenges.

PMID- 24583047
TI  - Poly(sucrose) micro particles preparation and their use as biomaterials.
AB  - Crosslinked p(sucrose) micro particles were synthesized for the first time from
      sucrose in water-in-oil microemulsion. Using divinyl sulfone (DVS) as crosslinker
      via reverse micelles of sodium bis(2-ethylhexyl) sulfosuccinate (AOT) p(sucrose)
      micro particles formed in a single step with very high yield (>90%). The
      particles have wide size distributions, and negative zeta potential, -27.30 mV,
      and can be made magnetic field responsive. P(sucrose) particles were shown to be
      degradable at pHs of 2.5 and 11. Dopamine and gallic acid were used as model
      drugs for absorption/release studies from p(sucrose) particles. Interestingly, it
      was shown that p(sucrose) microparticles can be a nutrient for Escherichia coli,
      and maybe used as a growth medium for other cells, bacteria and organisms.
      Additionally, the cytotoxic effect of p(sucrose) particles were determined as 26
      and 32.5% dead cells against MDA MB-231 cancerous cells and L929 fibroblast cells
      at 100 ug/ml concentration, respectively. P(sucrose) particles can be safely used
      for in vivo applications.

PMID- 24583049
TI  - Determinants of response to repeat hepatitis B vaccination in HIV-infected prior
      non-responders.

PMID- 24583050
TI  - The curse of a little of that human touch: is CGRP responsible?

PMID- 24583048
TI  - Chlorogenic acid prevents isoproterenol-induced hypertrophy in neonatal rat
      myocytes.
AB  - Cardiac hypertrophy is an independent risk factor for cardiovascular disease and
      its subsequent progression to heart failure represents a major cause of morbidity
      and mortality in the world. CGA is an important component of Chinese herbal
      medicine, acting as an antioxidant, scavenging free radicals and preventing
      inflammation. This study found that with the pre-treatment of chlorogenic acid in
      Iso-induced neonatal rat myocytes, the levels of the hypertrophic markers, ANP,
      BNP and beta-MHC decreased. The nuclear translocation of NF-kappaB was blocked,
      whereas NF-kappaBIA, an inhibitor of NF-kappaB, was upregulated accordingly. And
      the level of the intracellular ROS was also reduced. These data reveal that
      chlorogenic acid may inhibit Iso-induced cardiac hypertrophy by attenuating NF
      kappaB signaling pathway and suppressing ROS.

PMID- 24583051
TI  - Halogen bonding controls selectivity of FRET substrate probes for MMP-9.
AB  - Matrix metalloproteinases (MMPs) are a large family of zinc-dependent
      endoproteases that catalyze cleavage of extracellular matrix and nonmatrix
      proteins. MMPs play a role in tissue remodeling, and their uncontrolled activity
      is associated with number of diseases, including tumor metastasis. Thus, there is
      a need to develop methods to monitor MMP activity, and number of probes has been
      previously described. The key problem many probes encounter is the issue of
      selectivity, since 23 human MMPs, despite playing different physiological roles,
      have structurally similar active sites. Here, we introduce the halogen bonding
      concept into the probe design and show that the probe containing iodine exhibits
      an unprecedented selectivity for MMP-9. We provide structure-based explanation
      for the selectivity, confirming that it is due to formation of the halogen bond
      that supports catalysis, and we highlight the value of exploring halogen bonding
      in the context of selective probe design. 

PMID- 24583052
TI  - Target-selective phototherapy using a ligand-based photosensitizer for type 2
      cannabinoid receptor.
AB  - Phototherapy is a powerful, noninvasive approach for cancer treatment, with
      several agents currently in clinical use. Despite the progress and promise, most
      current phototherapy agents have serious side effects as they can lead to damage
      to healthy tissue, even when the photosensitizers are fused to targeting
      molecules due to nonspecific light activation of the unbound photosensitizer. To
      overcome these limitations, we developed a phototherapy agent that combines a
      functional ligand and a near infrared phthalocyanine dye. Our target is type 2
      cannabinoid receptor (CB2R), considered an attractive therapeutic target for
      phototherapy given it is overexpressed by many types of cancers that are located
      at a surface or can be reached by an endoscope. We show that our CB2R-targeted
      phototherapy agent, IR700DX-mbc94, is specific for CB2R and effective only when
      bound to the target receptor. Overall, this opens up the opportunity for
      development of an alternative treatment option for CB2R-positive cancers. 

PMID- 24583053
TI  - Sleeve gastrectomy reduces xanthine oxidase and uric acid in a rat model of
      morbid obesity.
AB  - BACKGROUND: Serum uric acid (sUA) plays a major role in the development of
      morbidities associated with obesity, especially cardiovascular diseases. Within
      the purine pathway, xanthine oxidase (XOD) represents the key enzyme. The aim of
      this study was to investigate the dynamics of sUA and XOD following sleeve
      gastrectomy (SG) in a rat model of high-fat-diet (HFD) induced obesity. PATIENTS:
      Over a period of 11 weeks, 30 rats received a HFD, and 10 rats received a low fat
      diet (LFD). Thereafter, 10 randomly selected HFD rats and 10 LFD rats were
      sacrificed. The remaining 20 HFD rats were randomly assigned to either SG or sham
      operation (SH) and studied 14 days postoperatively. METHODS: The white adipose
      tissues (WAT) from visceral (intestinal and retroperitoneal) and inguinal
      (subcutaneous) depots were collected. sUA and urine UA (uUA) were measured by
      high performance liquid chromatography-mass spectrometry (HPLC-MS/MS). Abundance
      and activity of XOD was investigated in the liver, colon, adipose tissue, and
      skeletal muscle by enzyme-linked immunosorbent assay (ELISA). RESULTS: HFD led to
      significant weight gain, elevated sUA levels, increased WAT and increase of XOD
      activity. Fourteen days postoperatively, SG rats showed a significant decrease of
      weight and adipose tissue, improved glucose metabolism, and changes of gut
      hormones. The sUA and uUA levels were significantly decreased following SG.
      Furthermore, XOD activity was significantly down-regulated in WAT. CONCLUSION:
      HFD induces elevated sUA levels by gain of WAT and increase of XOD activity.
      Following SG, the reduction of WAT as the major source of XOD and the lowering of
      XOD activity are the basis for the decrease of sUA.

PMID- 24583054
TI  - Genomic and epigenomic analyses of monozygotic twins discordant for congenital
      renal agenesis.
AB  - Monozygotic twins have been widely studied to distinguish genetic and
      environmental factors in the pathogenesis of human diseases. For renal agenesis,
      the one-sided absence of renal tissue, the relative contributions of genetic and
      environmental factors to its pathogenesis are still unclear. In this study of a
      pair of monozygotic twins discordant for congenital renal agenesis, the genomic
      profile was analyzed from a set of blood samples using high-throughput exome
      capture sequencing to detect single-nucleotide polymorphisms (SNPs), copy number
      variations (CNVs), and insertions and deletions (indels). Also, an epigenomic
      analysis used reduced-representation bisulfite sequencing to detect
      differentially methylated regions (DMRs). No discordant SNPs, CNVs, or indels
      were confirmed, but 514 DMRs were detected. KEGG analysis indicated the DMRs
      localized to 10 signaling pathways and 25 genes, including the mitogen-activated
      protein kinase pathway and 6 genes (FGF18, FGF12, PDGFRA, MAPK11, AMH, CTBP1)
      involved in organ development. Although methylation results from our adult
      patient and her sister may not represent the pattern that was present during
      kidney development, we could at least confirm a lack of obvious differences at
      the genome level, which suggests that nongenetic factors may be involved in the
      pathogenesis of renal agenesis. 

PMID- 24583055
TI  - Bioimpedance-guided fluid management in maintenance hemodialysis: a pilot
      randomized controlled trial.
AB  - BACKGROUND: Chronic subclinical volume overload happens very frequently in
      hemodialysis patients and is associated directly with hypertension, increased
      arterial stiffness, left ventricular hypertrophy, and ultimately higher
      mortality. STUDY DESIGN: Randomized controlled parallel-group trial. SETTING &
      PARTICIPANTS: 131 patients from one hemodialysis center, randomly assigned into 2
      groups. INTERVENTION: Dry weight prescription using results derived from repeated
      3-month bioimpedance measurements to guide ultrafiltration for strict volume
      control (bioimpedance group; n=62) compared with clinical judgment without
      bioimpedance measures (clinical-methods group; n=69) for 2.5 years. OUTCOMES: The
      primary outcome was all-cause mortality over 2.5 years (the duration of the
      intervention). Secondary outcomes were change in relative arterial stiffness,
      fluid overload, and blood pressure (BP) over 2.5 years. MEASUREMENTS:
      Bioimpedance measurements were performed using a Body Composition Monitor device.
      Pulse wave velocity analysis was performed at baseline, 2.5 years (end of
      intervention), and 3.5 years (end of study). Relative fluid overload and BP were
      assessed at 3-month intervals. RESULTS: The unadjusted HR for all-cause death in
      the bioimpedance group (vs the clinical-methods group) was 0.100 (95% CI, 0.013
      0.805; P=0.03). After 2.5 years, we found a greater decline in arterial
      stiffness, relative fluid overload, and systolic BP in the bioimpedance group
      than the clinical-methods group. Between-group differences in change from
      baseline to the end of intervention were -2.78 (95% CI, -3.75 to 1.80)m/s for
      pulse wave velocity (P<0.001), -2.99% (95% CI, -5.00% to -0.89%) for relative
      fluid overload (P=0.05), and -2.43 (95% CI, -7.70 to 2.84)mmHg for systolic BP
      (P=0.4). LIMITATIONS: Echocardiography was not performed as cardiovascular
      assessment and the caregivers were not masked to the intervention. CONCLUSIONS:
      Our study showed improvement in both surrogate and hard end points after strict
      volume control using bioimpedance to guide dry weight adjustment. These findings
      need to be confirmed in a larger trial.

PMID- 24583057
TI  - Recruitment to trials of late thrombolysis: lessons from the EXTEND study.
AB  - To increase the percentage of acute stroke patients benefiting from thrombolysis,
      the utility of expanding the time window of treatment beyond 4.5 hours after
      stroke onset needs to be investigated. We aimed to identify the target population
      and the challenges of recruitment of patients for the time window beyond 4.5
      hours. Extending the time for Thrombolysis in Emergency Neurological Deficits
      (EXTEND), a multicentre randomised controlled trial testing the efficacy of
      thrombolytic therapy in patients with clinically significant ischaemic penumbra
      between 4.5 to 9 hours after stroke onset, was used as a model to evaluate
      inclusion and exclusion criteria for late thrombolysis trials. Data from all
      stroke patients admitted to Austin Health over a 1 year period were
      retrospectively analysed. Case notes were examined to determine potential trial
      eligibility. Of 556 patients assessed, 95 (17%) presented during the EXTEND time
      window. Sixty-seven of these (70.5%) were wake-up strokes (WUS) and 28 (29.5%)
      arrived between 4.5 and 9 hours after symptoms onset. At least one exclusion
      criterion was found for 78 (82%) of them. Hence, 17 (3%) patients arrived within
      an appropriate time frame for the study without any exclusion criteria. Most of
      these (13) arrived outside routine MRI hours. The number of patients recruited
      would have increased more than three-fold if imaging had been available 24 hours,
      7 days a week. A significant proportion (17%) of ischaemic stroke patients
      presented between 4.5 and 9 hours after stroke onset. The majority of these were
      WUS. The major challenge identified for patient recruitment was imaging
      availability.

PMID- 24583056
TI  - PRAS40 plays a pivotal role in protecting against stroke by linking the Akt and
      mTOR pathways.
AB  - The proline-rich Akt substrate of 40kDa (PRAS40) protein is not only a substrate
      of the protein kinase Akt but also a component of the mTOR complex 1 (mTORC1),
      thus it links the Akt and the mTOR pathways. We investigated the potential
      protective role of PRAS40 in cerebral ischemia and its underlying mechanisms by
      using rats with lentiviral over-expression of PRAS40 and mice with PRAS40 gene
      knockout (PRAS40 KO). Our results show that gene transfer of PRAS40 reduced
      infarction size in rats by promoting phosphorylation of Akt, FKHR (FOXO1),
      PRAS40, and mTOR. In contrast, PRAS40 KO increased infarction size. Although the
      PRAS40 KO under normal condition did not alter baseline levels of phosphorylated
      proteins in the Akt and mTOR pathways, PRAS40 KO that underwent stroke exhibited
      reduced protein levels of p-S6K and p-S6 in the mTOR pathway but not p-Akt, or p
      PTEN in the Akt pathway. Furthermore, co-immunoprecipitation suggests that there
      were less interactive effects between Akt and mTOR in the PRAS40 KO. In
      conclusion, PRAS40 appears to reduce brain injury by converting cell signaling
      from Akt to mTOR. 

PMID- 24583058
TI  - Cocaine exposure prior to pregnancy alters the psychomotor response to cocaine
      and transcriptional regulation of the dopamine D1 receptor in adult male
      offspring.
AB  - There is evidence that maternal experience prior to pregnancy can play an
      important role in behavioral, physiological, and genetic programming of
      offspring. Likewise, exposure to cocaine in utero can result in marked changes in
      central nervous system function of offspring. In this study, we examined whether
      exposure of rat dams to cocaine prior to pregnancy subsequently alters indices of
      behavior, physiology, and gene expression in offspring. Multiple outcome measures
      were examined in adult male offspring: (1) behavioral expression of cocaine
      induced psychomotor activation; (2) levels of corticosterone in response to
      immobilization stress; and (3) expression of multiple genes, including dopamine
      receptor D1 (DRD1) and D2 (DRD2), glucocorticoid receptor (GR), and corticotropin
      releasing factor (CRF), in functionally relevant brain regions. Adult Sprague
      Dawley females were exposed to cocaine (15-30 mg/kg, i.p.) or saline for 10 days,
      and were then mated to drug naive males of the same strain. Separate groups of
      adult male offspring were tested for their acute psychomotor response to cocaine
      (0, 15, 30 mg/kg, i.p.), corticosterone responsivity to 20 min of immobilization
      stress, and expression of multiple genes using quantitative PCR. Offspring of
      dams exposed to cocaine prior to conception exhibited increased psychomotor
      sensitivity to cocaine, and upregulated gene expression of DRD1 in the medial
      prefrontal cortex (mPFC). Neither stress-induced corticosterone levels nor gene
      expression of GR or CRF genes were altered. These data suggest that cocaine
      exposure before pregnancy can serve to enhance psychomotor sensitivity to cocaine
      in offspring, possibly via alterations in dopamine function that include
      upregulation of the DRD1.

PMID- 24583059
TI  - Glutenase ALV003 attenuates gluten-induced mucosal injury in patients with celiac
      disease.
AB  - BACKGROUND & AIMS: Gluten ingestion leads to small intestinal mucosal injury in
      patients with celiac disease, necessitating strict life-long exclusion of dietary
      gluten. Despite adherence to a gluten-free diet, many patients remain symptomatic
      and still have small intestinal inflammation. In this case, nondietary therapies
      are needed. We investigated the ability of ALV003, a mixture of 2 recombinant
      gluten-specific proteases given orally, to protect patients with celiac disease
      from gluten-induced mucosal injury in a phase 2 trial. METHODS: We established
      the optimal daily dose of gluten to be used in a 6-week challenge study. Then, in
      the intervention study, adults with biopsy-proven celiac disease were randomly
      assigned to groups given ALV003 (n = 20) or placebo (n = 21) together with the
      daily gluten challenge. Duodenal biopsies were collected at baseline and after
      gluten challenge. The ratio of villus height to crypt depth and densities of
      intraepithelial lymphocytes were the primary end points. RESULTS: A daily dose of
      2 g gluten was selected for the intervention study. Sixteen patients given ALV003
      and 18 given placebo were eligible for efficacy evaluation. Biopsies from
      subjects in the placebo group showed evidence of mucosal injury after gluten
      challenge (mean villus height to crypt depth ratio changed from 2.8 before
      challenge to 2.0 afterward; P = .0007; density of CD3(+) intraepithelial
      lymphocytes changed from 61 to 91 cells/mm after challenge; P = .0003). However,
      no significant mucosal deterioration was observed in biopsies from the ALV003
      group. Between groups, morphologic changes and CD3(+) intraepithelial lymphocyte
      counts differed significantly from baseline to week 6 (P = .0133 and P = .0123,
      respectively). There were no statistically significant differences in symptoms
      between groups. CONCLUSIONS: Based on a phase 2 trial, the glutenase ALV003
      appears to attenuate gluten-induced small intestinal mucosal injury in patients
      with celiac disease in the context of an everyday gluten-free diet containing
      daily up to 2 g gluten. Clinicaltrial.gov, NUMBERS: NCT00959114 and NCT01255696.

PMID- 24583061
TI  - Development of Hong Kong Liver Cancer staging system with treatment
      stratification for patients with hepatocellular carcinoma.
AB  - BACKGROUND & AIMS: We aimed to develop a prognostic classification scheme with
      treatment guidance for Asian patients with hepatocellular carcinoma (HCC).
      METHODS: We collected data from 3856 patients with HCC predominantly related to
      hepatitis B treated at Queen Mary Hospital in Hong Kong from January 1995 through
      December 2008. Data on patient performance status, Child-Pugh grade, tumor status
      (size, number of nodules, and presence of intrahepatic vascular invasion), and
      presence of extrahepatic vascular invasion or metastasis were included, and
      randomly separated into training and test sets for analysis. Cox regression and
      classification and regression tree analyses were used to account for the relative
      effects of factors in predicting overall survival times and to classify disparate
      treatment decision rules, respectively; the staging system and treatment
      recommendation then were constructed by integration of clinical judgments. The
      Hong Kong Liver Cancer (HKLC) classification was compared with the Barcelona
      Clinic Liver Cancer (BCLC) classification in terms of discriminatory ability and
      effectiveness of treatment recommendation. RESULTS: The HKLC system had
      significantly better ability than the BCLC system to distinguish between patients
      with specific overall survival times (area under the receiver operating
      characteristic curve values, approximately 0.84 vs 0.80; concordance index, 0.74
      vs 0.70). More importantly, HKLC identified subsets of BCLC intermediate- and
      advanced-stage patients for more aggressive treatments than what were recommended
      by the BCLC system, which improved survival outcomes. Of BCLC-B patients
      classified as HKLC-II in our system, the survival benefit of radical therapies,
      compared with transarterial chemoembolization, was substantial (5-year survival
      probability, 52.1% vs 18.7%; P < .0001). In BCLC-C patients classified as HKLC
      II, the survival benefit of radical therapies compared with systemic therapy was
      even more pronounced (5-year survival probability, 48.6% vs 0.0%; P < .0001).
      CONCLUSIONS: We collected data from patients with HCC in Hong Kong to create a
      system to identify patients who are suitable for more aggressive treatment than
      the currently used BCLC system. The HKLC system should be validated in non-Asian
      patient populations and in patients with different etiologies of HCC.

PMID- 24583060
TI  - Secretin stimulates biliary cell proliferation by regulating expression of
      microRNA 125b and microRNA let7a in mice.
AB  - BACKGROUND & AIMS: Proliferating cholangiocytes secrete and respond to
      neuroendocrine hormones, including secretin. We investigated whether secretin
      secreted by S cells and cholangiocytes stimulates biliary proliferation in mice.
      METHODS: Cholestasis was induced in secretin knockout (Sct(-/-)) and wild-type
      (control) mice by bile duct ligation (BDL). At days 3 and 7 after BDL, control
      and Sct(-/-) mice received tail-vein injections of morpholinos against microRNA
      125b or let7a. One week later, liver tissues and cholangiocytes were collected.
      Immunohistochemical, immunoblot, luciferase reporter, and real-time polymerase
      chain reaction assays were performed. Intrahepatic bile duct mass (IBDM) and
      proliferation were measured. Secretin secretion was measured in conditioned media
      from cholangiocytes and S cells and in serum and bile. RESULTS: Secretin
      secretion was increased in supernatants from cholangiocytes and S cells and in
      serum and bile after BDL in control mice. BDL Sct(-/-) mice had lower IBDM,
      reduced proliferation, and reduced production of vascular endothelial growth
      factor (VEGF) A and nerve growth factor (NGF) compared with BDL control. BDL and
      control mice given morpholinos against microRNA 125b or let7a had increased IBDM.
      Livers of mice given morpholinos against microRNA 125b had increased expression
      of VEGFA, and those treated with morpholinos against microRNA let7a had increased
      expression of NGF. Secretin regulated VEGF and NGF expression that negatively
      correlated with microRNA 125b and let7a levels in liver tissue. CONCLUSIONS:
      After liver injury, secretin produced by cholangiocytes and S cells reduces
      microRNA 125b and let7a levels, resulting in up-regulation of VEGF and NGF.
      Modulation of cholangiocyte expression of secretin could be a therapeutic
      approach for biliary diseases.

PMID- 24583062
TI  - Mortality, liver transplantation, and hepatocellular carcinoma among patients
      with chronic hepatitis B treated with entecavir vs lamivudine.
AB  - BACKGROUND & AIMS: Little is known about whether the antiviral agent entecavir is
      more effective than a less potent drug, lamivudine, in reducing the risk of death
      and hepatocellular carcinoma (HCC) in patients with chronic hepatitis B. METHODS:
      We performed a retrospective analysis of data from 5374 consecutive adult
      patients with chronic hepatitis B, treated with entecavir (n = 2000) or
      lamivudine (n = 3374), at a tertiary referral hospital in Seoul, Korea, from
      November 1, 1999, through December 31, 2011. Data were collected from patients
      for up to 6 years and analyzed by a multivariable Cox proportional hazards model
      for the entire cohort and for propensity score-matched cohorts. RESULTS: During
      the study period, 302 patients (5.6%) died, 169 (3.1%) received a liver
      transplant, and 525 (9.8%) developed HCC. Multivariable analyses showed that
      compared with lamivudine, entecavir therapy was associated with a significantly
      lower risk of death or transplantation (hazard ratio [HR], 0.49; 95% confidence
      interval [CI], 0.38-0.64), but a similar risk of HCC (HR, 1.08; 95% CI, 0.87
      1.34). In the 1792 overall propensity-matched pairs, entecavir again was
      associated with a significantly lower risk of death or transplantation (HR, 0.49;
      95% CI, 0.37-0.64) and a similar risk of HCC (HR, 1.01; 95% CI, 0.80-1.27).
      Entecavir also reduced the risk of death or transplantation, compared with
      lamivudine, in 860 pairs of patients with cirrhosis (HR, 0.42; 95% CI, 0.31-0.57)
      but there were no differences in risk for HCC (HR, 1.00; 95% CI, 0.78-1.28).
      However, entecavir and lamivudine did not have significantly different effects on
      clinical outcome in 878 pairs of patients without cirrhosis. CONCLUSIONS: In a
      retrospective study of 5374 patients with chronic hepatitis B virus infection,
      entecavir therapy was associated with a significantly lower risk of death or
      transplantation than lamivudine. However, the drugs did not have different
      effects on HCC risk.

PMID- 24583064
TI  - Association between hepatitis E and neurological disorders: two case studies and
      literature review.
AB  - Hepatitis E (HEV) is an emerging disease in our developed countries, but is not
      routinely tested for in case of liver cytolysis. However, a growing number of
      extra-hepatic manifestations of HEV infection associated with acute hepatitis are
      reported. In this article, we discuss two cases of HEV with neurological
      symptoms, one with encephalitis, and the other with Parsonage Turner syndrome.
      All these disorders appeared concomitantly with liver cytolysis and disappeared
      quickly, following the viral kinetics. Only twenty cases of neurological
      manifestation of HEV have been described before. The use of HEV serology in
      patients with concurrent liver cytolysis and neurological symptoms has to be
      improved. 

PMID- 24583065
TI  - The causes of reduced proton-pumping efficiency in type B and C respiratory heme
      copper oxidases, and in some mutated variants of type A.
AB  - The heme-copper oxidases may be divided into three categories, A, B, and C, which
      include cytochrome c and quinol-oxidising enzymes. All three types are known to
      be proton pumps and are found in prokaryotes, whereas eukaryotes only contain A
      type cytochrome c oxidase in their inner mitochondrial membrane. However, the
      bacterial B- and C-type enzymes have often been reported to pump protons with an
      H(+)/e(-) ratio of only one half of the unit stoichiometry in the A-type enzyme.
      We will show here that these observations are likely to be the result of
      difficulties with the measuring technique together with a higher sensitivity of
      the B- and C-type enzymes to the protonmotive force that opposes pumping. We find
      that under optimal conditions the H(+)/e(-) ratio is close to unity in all the
      three heme-copper oxidase subfamilies. A higher tendency for proton leak in the B
      and C-type enzymes may result from less efficient gating of a proton pump
      mechanism that we suggest evolved before the so-called D-channel of proton
      transfer. There is also a discrepancy between results using whole bacterial cells
      vs. phospholipid vesicles inlaid with oxidase with respect to the observed proton
      pumping after modification of the D-channel residue asparagine-139 (Rhodobacter
      sphaeroides numbering) to aspartate in A-type cytochrome c oxidase. This
      discrepancy might also be explained by a higher sensitivity of proton pumping to
      protonmotive force in the mutated variant. This article is part of a Special
      Issue entitled: 18th European Bioenergetic Conference. 

PMID- 24583063
TI  - Antibiotic prophylaxis in hematopoietic stem cell transplantation. A meta
      analysis of randomized controlled trials.
AB  - OBJECTIVES: We performed a meta-analysis to evaluate the impact of systemic
      antibiotic prophylaxis in hematopoietic stem cell transplantation (HSCT)
      recipients. METHODS: We collected reports from PubMed, the Cochrane Library,
      EMBASE, CINAHL, and Web of Science, along with references cited therein. We
      included prospective, randomized studies on systemic antibiotic prophylaxis in
      HSCT recipients. RESULTS: Seventeen trials with 1453 autologous and allogeneic
      HSCT recipients were included. Systemic antibiotic prophylaxis was compared with
      placebo or no prophylaxis in 10 trials and with non-absorbable antibiotics in two
      trials. Systemic antibiotics other than fluoroquinolones were evaluated in five
      of these 12 trials. Four trials evaluated the effect of the addition of
      antibiotics for gram-positive bacteria to fluoroquinolones. One trial compared
      two different systemic antibiotic regimens: fluoroquinolones versus trimethoprim
      sulfamethoxazole. As a result, systemic antibiotic prophylaxis reduced the
      incidence of febrile episodes (OR 0.16; 95%CI 0.09-0.30), clinically or
      microbiologically documented infection (OR 0.38; 95%CI 0.22-0.63) and bacteremia
      (OR 0.31; 95%CI 0.16-0.59) without significantly affecting all-cause mortality or
      infection-related mortality. CONCLUSIONS: Systemic antibiotic prophylaxis
      successfully reduced the incidence of infection. However, there was no
      significant impact on mortality. The clinical benefits of prophylaxis with
      fluoroquinolones were inconclusive because of the small number of clinical trials
      evaluated.

PMID- 24583066
TI  - Crepitus is a first indication of patellofemoral osteoarthritis (and not of
      tibiofemoral osteoarthritis).
AB  - OBJECTIVE: The patellofemoral joint (PFJ) is important in early detection of knee
      osteoarthritis (OA). Little is known about the relationship between specific
      clinical findings and PFJ Magnetic resonance Imaging (MRI) features. The
      objective was to examine the relationship between (early) clinical findings and
      PFJ MRI features in females (45-60 years) without knee OA (PFJ or tibiofemoral
      joint (TFJ) OA) based on a recently suggested MRI definition. METHODS: MRIs of
      knees of women of a sub-study of the Rotterdam Study were scored with semi
      quantitative scoring. Specific patellar tests were performed on physical
      examination. Current knee pain and history of patellar knee pain were reported.
      Binomial logistic generalized estimated equations were used to determine the
      association between clinical findings of OA and PFJ MRI features. All
      associations were adjusted for age, body mass index (BMI) and TFJ MRI features.
      RESULTS: In 888 women (1776 knees, mean age: 55.1 years and mean BMI: 27.0
      kg/m(2)) we found significant associations between crepitus and all PFJ MRI
      features (Odds ratios (OR) range: 2.61-5.49). A history of patellar pain was
      significantly associated with almost all PFJ MRI features (ORcartilage: 1.95;
      ORcysts: 1.86; ORbone marrow lesions: 1.83), except for osteophytes. No
      significant associations were found between the clinical findings and TFJ MRI
      features. CONCLUSION: Crepitus and history of patellar pain are clinical findings
      that indicate PFJ lesions seen on MRI. These tests could help to indicate signs
      of PFJOA. Follow-up data needs to confirm whether these tests have an additional
      diagnostic value for early knee OA in PFJ or TFJ.

PMID- 24583067
TI  - Response to letter to the Editor: comment on Corbett et al. entitled "Acupuncture
      and other physical treatments for the relief of pain due to osteoarthritis of the
      knee: network meta-analysis".

PMID- 24583069
TI  - Anti-tumor activity and relative mechanism of ethanolic extract of Marsdenia
      tenacissima (Asclepiadaceae) against human hematologic neoplasm in vitro and in
      vivo.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Marsdenia tenacissima, a traditional Chinese
      medicinal herb, endemic to Yunnan Province is widely used to treat cough, asthma,
      expectorant, esophageal cancer, gastric cancer, lung cancer, and hepatocellular
      carcinoma. The aim of this study was to evaluate in vitro and in vivo anti
      hematologic neoplasm potential of the ethanolic extract of this herb (crude
      ethanolic extract of Marsdenia tenacissima, CME) and by using different assays to
      elucidate its possible mechanism of action. MATERIALS AND METHODS: The
      cytotoxicity of CME on tumor cells and peripheral blood mononuclear cells (PBMCs)
      was evaluated using MTT and apoptosis assays. We also tested the effect of CME on
      colony formation inhibition and cell cycle distribution of tumor cells. The
      protein expressions of Cyclin D1, Bax, Bcl-2, caspase-3 and caspase-9 were
      detected through Western blotting. In vivo anti-tumor effect was evaluated by
      measuring tumor volume changes, measuring tumor weight, evaluation of tumor
      microvessel density (MVD) and TUNEL staining by using immunohistochemistry
      staining in tumor models of nude mice. RESULTS: Marsdenia tenacissima ethanolic
      extract exhibited effects of proliferation inhibition and induction of apoptosis
      on human hematologic neoplasm tumor cells in vitro, as well as hematologic
      neoplasm growth in vivo. CONCLUSION: This study clearly indicated that the
      ethanolic extract of Marsdenia tenacissima displayed strong anti-tumor effects
      against hematologic neoplasm cells and could induce tumor cells apoptosis in
      vitro and in vivo, and also had a significant anti-angiogenic effect in vivo
      against tumor cell apoptosis. Its multi-mechanism of action might be associated
      with the cell cycle (G0/G1) arrest, induction of apoptosis through up-regulation
      protein expressions of Bax, caspase-9 and caspase-3 genes and down-regulation of
      the expressions of Cyclin D1 and Bcl-2 genes, a decrease in tumor microvessel
      density and an increase of TUNEL-positive cells in vivo. These findings provided
      the molecular theoretical basis of clinical application.

PMID- 24583068
TI  - IFN-gamma AU-rich element removal promotes chronic IFN-gamma expression and
      autoimmunity in mice.
AB  - We generated a mouse model with a 162 nt AU-rich element (ARE) region deletion in
      the 3' untranslated region (3'UTR) of the interferon-gamma (IFN-gamma) gene that
      results in chronic circulating serum IFN-gamma levels. Mice homozygous for the
      ARE deletion (ARE-Del) (-/-) present both serologic and cellular abnormalities
      typical of patients with systemic lupus erythematosus (SLE). ARE-Del(-/-) mice
      display increased numbers of pDCs in bone marrow and spleen. Addition of IFN
      gamma to Flt3-ligand (Flt3L) treated in vitro bone marrow cultures results in a 2
      fold increase in pDCs with concurrent increases in IRF8 expression. Marginal zone
      B (MZB) cells and marginal zone macrophages (MZMs) are absent in ARE-Del(-/-)
      mice. ARE-Del(+/-) mice retain both MZB cells and MZMs and develop no or mild
      autoimmunity. However, low dose clodronate treatment in ARE-Del(+/-) mice
      specifically eliminates MZMs and promotes anti-DNA antibody development and
      glomerulonephritis. Our findings demonstrate the consequences of a chronic IFN
      gamma milieu on B220(+) cell types and in particular the impact of MZB cell loss
      on MZM function in autoimmunity. Furthermore, similarities between disease states
      in ARE-Del(-/-) mice and SLE patients suggest that IFN-gamma may not only be a
      product of SLE but may be critical for disease onset and progression. 

PMID- 24583070
TI  - Cytotoxicity and modes of action of five Cameroonian medicinal plants against
      multi-factorial drug resistance of tumor cells.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Beilschmiedia acuta Kosterm, Clausena anisata
      (Willd) Hook, Fagara tessmannii Engl., Newbouldia laevis Seem., and Polyscias
      fulva (Hiern) Harms. are medicinal plants used in Cameroonian traditional
      medicine in the treatment of various types of cancers. The present study aims at
      investigating 11 methanolic extracts from the above Cameroonian medicinal plants
      on a panel of human cancer cell lines, including various drug-resistant
      phenotypes. Possible modes of action were analyzed for two extracts from
      Beilschmiedia acuta and Polyscia fulva and alpha-hederin, the representative
      constituent of Polyscia fulva. MATERIALS AND METHODS: Cytotoxicity was determined
      using a resazurin assay. Cell cycle, apoptosis, mitochondrial membrane potential
      (MMP), and reactive oxygen species (ROS) were measured by flow cytometry.
      Cellular response to alpha-hederin was investigated by a mRNA microarray
      approach. RESULTS: Prescreening of extracts (40ug/mL) showed that three of eleven
      plant extracts inhibited proliferation of CCRF-CEM cells by more than 50%, i.e.
      BAL (73.65%), the bark extract of Beilschmiedia acuta (78.67%) and PFR (68.72%).
      Subsequent investigations revealed IC50 values below or around 30ug/mL of BAL and
      PFR in 10 cell lines, including drug-resistant models, i.e. P-glycoprotein
      overexpressing CEM/ADR5000, breast cancer resistance protein-transfected MDA-MB
      231-BCRP, TP53 knockout cells (HCT116 p53(-/-)), and mutation-activated epidermal
      growth factor receptor-transfected U87MG.DeltaEGFR cells. IC50 values below
      5ug/mL of BAL were obtained for HCT116 (p53(-/-)) cells. IC50 values below 10uM
      of alpha-hederin were found for sensitive CCRF-CEM and multidrug-resistant
      CEM/ADR5000 cells. The BAL and PFR extracts induced cell cycle arrest between
      G0/G1 and S phases. PFR-induced apoptosis was associated with increased ROS
      generation and MMP breakdown. Microarray-based cluster analysis revealed a gene
      expression profile that predicted cellular response to alpha-hederin. CONCLUSION:
      BAL, PFL and alpha-hederin, an exemplarily taken constituent of Beilschmiedia
      acuta and Polyscia fulva extracts revealed cytotoxicity towards cancer cell
      lines. Hence, Beilschmiedia acuta and Polyscia fulva may be valuable to develop
      drugs against otherwise drug-resistant cancer cells.

PMID- 24583071
TI  - Ethnobotanical survey of medicinal plants used in the management of skin
      disorders among the Xhosa communities of the Amathole District, Eastern Cape,
      South Africa.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Skin diseases have been of major concern recently
      due to the association of skin opportunistic infections and HIV/AIDS, are usually
      the first sign of HIV infection and conversion to AIDS. More than 90% of HIV
      infected individuals develop skin and mucosal complications at some stage during
      the disease. Although classical medicine is undoubtedly addressing these
      diseases, the people of the Eastern Cape, South Africa still depend, to a large
      extent on traditional herbal medicine for the treatment of various diseases. The
      current study was undertaken to investigate the local peoples characterisation of
      skin diseases/disorders and to document the medicinal plants used for various
      skin disorders among the Xhosa-speaking communities of the Amathole District,
      Eastern Cape. MATERIALS AND METHODS: Information was obtained by interviewing 54
      respondents in 7 locations. Collection of the reported medicinal plants from the
      wild was assisted by the informants and identification of the collected plants
      specimens was done with the help of floristic works of South Africa. Quantitative
      methods including the use-value and the informant consensus factor (ICF) were
      computed for determining the relative importance of species known locally and the
      homogeneity of the informants' knowledge respectively. RESULTS: Twenty five skin
      disorders, classified under 5 categories are being treated with the listed
      medicinal plants in the study area. The highest ICF (0.45) was linked to bacteria
      related skin disorders. This category comprised of 57 use citations, 3 skin
      disorders; with sore throat being the most frequently mentioned (4.2%). In this
      study, 106 plant species distributed in 61 families and 107 genera were
      identified as being used to treat one or more of the skin disorders. The species
      with the highest use-value was Aloe ferox Mill. (Xanthorrhoeaceae) known locally
      as Umhlaba. The most representative families were Solanaceae and Asteraceae with
      6 species each, followed by Fabaceae, Poaceae and Rutaceae (5 species each). The
      leaves were the most frequently used plant part, followed by the bark (10%) and
      fruits (7%). Administration of the different plant parts was mostly topical (77%)
      on the affected area. CONCLUSION: A total of twenty five skin
      disorders/conditions, classified under 5 categories are being treated with the
      listed medicinal plants in the study area. 106 plant species distributed in 61
      families and 107 genera were identified as being used to treat one or more of the
      skin disorders. The species with the highest use-value was Aloe ferox Mill.
      (Xanthorrhoeaceae) known locally as Umhlaba. The most representative families
      were Solanaceae, Asteraceae, Fabaceae, Poaceae, Rutaceae and Euphorbiaceae.
      Majority of the plant species were herbs and the leaves were the most frequently
      used, mostly applied topically as a paste, powder or sap on the affected skin
      area.

PMID- 24583072
TI  - Antidiabetic effect of flavonoids from Malus toringoides (Rehd.) Hughes leaves in
      diabetic mice and rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The leaf of Malus toringoides (Rehd.) Hughes is a
      traditional folk medicine in Tibet, China, which is called "E Se" in Tibetan
      language. This original plant grows on snow mountains at an attitude of 3000 to
      3700 m. It is primarily used to treat hypertension, hyperlipidemia,
      hyperglycemia, indigestion and other diseases. This study aimed to evaluate the
      antidiabetic effect of flavonoids extracted from E Se (ESF) and to explore the
      potential mechanism in streptozotocin (STZ) or alloxan (ALX) induced diabetic
      mice and STZ-induced diabetic rats. MATERIALS AND METHODS: 72 h after the
      establishment of a diabetic model, STZ or ALX induced diabetic mice and STZ
      induced diabetic rats were treated daily with ESF at doses of 45, 90, 180 mg/kg
      and 37.5, 75, 150 mg/kg, respectively. Both mice and rats were fasted for 5h
      before administration and the blood glucose (BG) levels were tested 1h after
      treatment. Body weight was determined every other day. For STZ-induced rats,
      glycosylated hemoglobin (Hb1Ac), serum insulin and c-peptide, hepatic glycogen,
      superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels in liver
      were assessed on the fourth day after BG level detection. RESULTS: Compared with
      the model group, the general behavior of mice treated with ESF (90, 180 mg/kg)
      and rats treated with ESF (75, 150 mg/kg) became better and BG levels were
      significantly reduced (P<0.05). Significant decrease (P<0.05) in Hb1Ac level was
      observed in ESF-treated rats compared with diabetic rats. Significant increase
      (P<0.05 ) in serum insulin and c-peptide were detected in ESF-treated rats. The
      treatment also significantly (P<0.05) elevated SOD activity and reduced MDA level
      in the liver of diabetic rats. Besides, ESF 150 mg/kg had a trend of rising
      hepatic glycogen content of diabetic rats. CONCLUSIONS: The findings of this
      study suggest that flavonoids from the Malus toringoides (Rehd.) Hughes leaves
      may possess an antidiabetic activity in animals with established diabetes.

PMID- 24583074
TI  - The dynamic microbiome.
AB  - While our genomes are essentially static, our microbiomes are inherently dynamic.
      The microbial communities we harbor in our bodies change throughout our lives due
      to many factors, including maturation during childhood, alterations in our diets,
      travel, illnesses, and medical treatments. Moreover, there is mounting evidence
      that our microbiomes change us, by promoting health through their beneficial
      actions or by increasing our susceptibility to diseases through a process termed
      dysbiosis. Recent technological advances are enabling unprecedentedly detailed
      studies of the dynamics of the microbiota in animal models and human populations.
      This review will highlight key areas of investigation in the field, including
      establishment of the microbiota during early childhood, temporal variability of
      the microbiome in healthy adults, responses of the microbiota to intentional
      perturbations such as antibiotics and dietary changes, and prospective analyses
      linking changes in the microbiota to host disease status. Given the importance of
      computational methods in the field, this review will also discuss issues and
      pitfalls in the analysis of microbiome time-series data, and explore several
      promising new directions for mathematical model and algorithm development. 

PMID- 24583073
TI  - New insights into the role of connexins in pancreatic islet function and
      diabetes.
AB  - Multi-cellular systems require complex signaling mechanisms for proper tissue
      function, to mediate signaling between cells in close proximity and at distances.
      This holds true for the islets of Langerhans, which are multicellular micro
      organs located in the pancreas responsible for glycemic control, through
      secretion of insulin and other hormones. Coupling of electrical and metabolic
      signaling between islet beta-cells is required for proper insulin secretion and
      effective glycemic control. beta-cell specific coupling is established through
      gap junctions composed of connexin36, which results in coordinated insulin
      release across the islet. Islet connexins have been implicated in both Type-1 and
      Type-2 diabetes; however a clear link remains to be determined. The goal of this
      review is to discuss recent discoveries regarding the role of connexins in
      regulating insulin secretion, the regulation of connexins within the islet, and
      recent studies which support a role for connexins in diabetes. Further studies
      which investigate the regulation of connexins in the islet and their role in
      diabetes may lead to novel diabetes therapies which regulate islet function and
      beta-cell survival through modulation of gap junction coupling. 

PMID- 24583075
TI  - S-nitrosylation influences the structure and DNA binding activity of AtMYB30
      transcription factor from Arabidopsis thaliana.
AB  - MYB proteins are a family of transcription factors that play an important role in
      plant development and regulatory defense processes. Arabidopsis thaliana MYB30
      (AtMYB30), a member of this protein family, is involved in cell death processes
      during the hypersensitive response (HR) of plants. HR is characterized by a vast
      production of reactive oxygen species (ROS) and nitric oxide (NO). NO may thus
      influence the binding of AtMYB30 to DNA. In this work we evaluated the effect of
      NO on AtMYB30 DNA binding activity, and also in the protein structural
      properties. A fully active minimal DNA-binding domain (DBD) of AtMYB30 (residues
      11-116) containing two cysteine residues (C49 and C53) was overexpressed and
      purified. Site-directed mutagenesis was used to obtain AtMYB30 DBD mutants C49A
      and C53A. The DNA binding activity of AtMYB30 DBD, and Cys single mutants is
      clearly inhibited upon incubation with a NO donor, and S-nitrosylation was
      confirmed by the biotin switch assay. Finally, in order to understand the
      mechanism of NO effect on AtMYB30 DNA binding activity we performed circular
      dichroism analysis, to correlate the observed protein function inhibition and a
      potential structural impairment on AtMYB30 DBD. Indeed, NO modification of C49
      and C53 residues promotes a subtle modification on the secondary structure of
      this transcription factor. We thus demonstrated, using various techniques, the in
      vitro effect of NO on AtMYB30 DBD, and thus the potential consequences of NO
      activity on plant metabolism influenced by this transcription factor. 

PMID- 24583076
TI  - A rapid and efficient method for neuronal induction of the P19 embryonic
      carcinoma cell line.
AB  - BACKGROUND: P19 mouse embryonic carcinoma cells are conventionally induced to
      differentiate into neural cells by suspension culture in the presence of retinoic
      acid to form cell aggregates, followed by adhesion culture in a poly-l-lysine
      coated dish. Drawbacks of this procedure include it taking more than 10 days to
      obtain mature neurons, and non-neuronal proliferating cells occupying the
      majority of the cell population with time. NEW METHOD: Here, we show a novel
      method for the rapid and efficient neurogenesis of P19 cells, without aggregate
      formation in a suspension culture. The new approach is based on an adherent serum
      free culture in a laminin-coated dish in the presence of FGF8, a gamma-secretase
      inhibitor, and cytosine arabinoside. RESULTS: The new method efficiently induced
      P19 cells to differentiate into neurons within 4 days, and subsequently into
      mature neurons that were responsive to several neurotransmitters, giving
      spontaneous neuronal network activity within 6 days. COMPARISON WITH EXISTING
      METHOD: The novel method accelerated neuritogenesis and enhanced population of
      neuron selectively compared to the conventional method. Proliferating non
      neuronal cells were eliminated by adding cytosine arabinoside during neuronal
      maturation. CONCLUSIONS: The method is useful for studying neuronal
      differentiation or activities.

PMID- 24583077
TI  - AAV vector-mediated secretion of chondroitinase provides a sensitive tracer for
      axonal arborisations.
AB  - As part of a project to express chondroitinase ABC (ChABC) in neurons of the
      central nervous system, we have inserted a modified ChABC gene into an adeno
      associated viral (AAV) vector and injected it into the vibrissal motor cortex in
      adult rats to determine the extent and distribution of expression of the enzyme.
      A similar vector for expression of green fluorescent protein (GFP) was injected
      into the same location. For each vector, two versions with minor differences were
      used, giving similar results. After 4 weeks, the brains were stained to show GFP
      and products of chondroitinase digestion. Chondroitinase was widely expressed,
      and the AAV-ChABC and AAV-GFP vectors gave similar expression patterns in many
      respects, consistent with the known projections from the directly transduced
      neurons in vibrissal motor cortex and adjacent cingulate cortex. In addition,
      diffusion of vector to deeper neuronal populations led to labelling of remote
      projection fields which was much more extensive with AAV-ChABC than with AAV-GFP.
      The most notable of these populations are inferred to be neurons of cortical
      layer 6, projecting widely in the thalamus, and neurons of the anterior pole of
      the hippocampus, projecting through most of the hippocampus. We conclude that,
      whereas GFP does not label the thinnest axonal branches of some neuronal types,
      chondroitinase is efficiently secreted from these arborisations and enables their
      extent to be sensitively visualised. After 12 weeks, chondroitinase expression
      was undiminished. 

PMID- 24583078
TI  - Manganese enhanced magnetic resonance imaging (MEMRI): a powerful new imaging
      method to study tinnitus.
AB  - Manganese enhanced magnetic resonance imaging (MEMRI) is a method used primarily
      in basic science experiments to advance the understanding of information
      processing in central nervous system pathways. With this mechanistic approach,
      manganese (Mn(2+)) acts as a calcium surrogate, whereby voltage-gated calcium
      channels allow for activity driven entry of Mn(2+) into neurons. The detection
      and quantification of neuronal activity via Mn(2+) accumulation is facilitated by
      "hemodynamic-independent contrast" using high resolution MRI scans. This review
      emphasizes initial efforts to-date in the development and application of MEMRI
      for evaluating tinnitus (the perception of sound in the absence of overt acoustic
      stimulation). Perspectives from leaders in the field highlight MEMRI related
      studies by comparing and contrasting this technique when tinnitus is induced by
      high-level noise exposure and salicylate administration. Together, these studies
      underscore the considerable potential of MEMRI for advancing the field of
      auditory neuroscience in general and tinnitus research in particular. Because of
      the technical and functional gaps that are filled by this method and the prospect
      that human studies are on the near horizon, MEMRI should be of considerable
      interest to the auditory research community. This article is part of a Special
      Issue entitled <Annual Reviews 2014>. 

PMID- 24583079
TI  - Intracerebral administration of ultrasound-induced dissolution of lipid-coated
      GDNF microbubbles provides neuroprotection in a rat model of Parkinson's disease.
AB  - Parkinson's disease (PD) is a neurodegenerative disease characterized by loss of
      dopaminergic neurons in the substantia nigra. Neurotrophic factors, such as glial
      cell derived neurotrophic factor (GDNF), have been shown to provide a
      neuroprotective effect in PD rats. We have previously reported that ultrasound
      induced lipid-coated GDNF microspheres, which release GDNF in a sustained manner
      after low frequency ultrasound stimulation, can reduce hypoxic-ischemic injury in
      neonatal rats. In the present study, we investigated whether lipid-coated GDNF
      microspheres can provide a neuroprotective effect in a rat model of PD. After a
      rat model of PD was produced by 6-hydroxydompamine (6-OHDA) injections, lipid
      coated GDNF microspheres (1.5mg/kg) were injected into the striatum of PD rats.
      We found that GDNF levels were increased in the striatum of PD rats after lipid
      coated GDNF microspheres administration following low frequency ultrasound
      stimulation (20kHz, 5min per day, daily for 4 weeks). Moreover, GDNF microspheres
      reduced apomorphine-induced rotations, and increased striatal dopamine and nigral
      tyrosine hydroxylase (TH) levels in PD rats. Additionally, GDNF microspheres
      reduced caspase-3, tumor necrosis factor-alpha, matrix metalloproteinase 9 (MMP
      9) and OX-6 levels induced by 6-OHDA injections in PD rats. These data indicated
      that lipid-coated GDNF microspheres can provide a neuroprotective effect in PD
      rats.

PMID- 24583080
TI  - A neuroproteomic and systems biology analysis of rat brain post intracerebral
      hemorrhagic stroke.
AB  - Intracerebral hemorrhage (ICH) is a devastating form of stroke leading to a high
      rate of death and disability worldwide. Although it has been hypothesized that
      much of the IHC insult occurs in the subacute period mediated via a series of
      complex pathophysiological cascades, the molecular mechanisms involved in ICH
      have not been systematically characterized. Among the best approaches to
      understand the underlying mechanisms of injury and recovery, protein dynamics
      assessment via proteomics/systems biology platforms represent one of the cardinal
      techniques optimized for mechanisms investigation and biomarker identification. A
      proteomics approach may provide a biomarker focused framework from which to
      identify candidate biomarkers of pathophysiological processes involved in brain
      injury after stroke. In this work, a neuroproteomic approach (LC-MS/MS) was
      applied to investigate altered expression of proteins that are induced in brain
      tissue 3 h after injury in a rat model of ICH. Data from sham and focal ischemic
      models were also obtained and used for comparison. Based on the differentially
      expressed protein profile, systems biology analysis was conducted to identify
      associated cellular processes and related interaction maps. After LC-MS/MS
      analysis of the 3 h brain lysates, 86 proteins were differentially expressed
      between hemorrhagic and sham tissues. Furthermore, 38 proteins were
      differentially expressed between ischemic and sham tissues. On the level of
      global pathway analysis, hemorrhagic stroke proteins were shown to be involved in
      autophagy, ischemia, necrosis, apoptosis, calpain activation, and cytokine
      secretion. Moreover, ischemic stroke proteins were related to cell death,
      ischemia, inflammation, oxidative stress, caspase activation and apoptotic
      injury. In conclusion, the proteomic responses identified in this study provide
      key information about target proteins involved in specific pathological pathways.

PMID- 24583081
TI  - Characterization of the small RNA content of Trypanosoma cruzi extracellular
      vesicles.
AB  - A growing body of evidence in mammalian cells indicates that secreted vesicles
      can be used to mediate intercellular communication processes by transferring
      various bioactive molecules, including mRNAs and microRNAs. Based on these
      findings, we decided to analyze whether Trypanosoma cruzi-derived extracellular
      vesicles contain RNA molecules and performed a deep sequencing and genome-wide
      analysis of a size-fractioned cDNA library (16-40nt) from extracellular vesicles
      secreted by noninfective epimastigote and infective metacyclic trypomastigote
      forms. Our data show that the small RNAs contained in these extracellular
      vesicles originate from multiple sources, including tRNAs. In addition, our
      results reveal that the variety and expression of small RNAs are different
      between parasite stages, suggesting diverse functions. Taken together, these
      observations call attention to the potential regulatory functions that these RNAs
      might play once transferred between parasites and/or to mammalian host cells. 

PMID- 24583082
TI  - Design of novel cell penetrating peptides for the delivery of trehalose into
      mammalian cells.
AB  - Stabilization of cells in a desiccated state can significantly simplify the
      storage and transportation and save expenses for clinical applications.
      Introduction of the impermeable disaccharide, trehalose, into cells is an
      important step to improve the desiccation tolerance of cells. In this study, a
      novel cell penetrating peptide, KRKRWHW, was developed based on molecular
      simulations. The peptide exhibited little cytotoxicity and high penetrating
      efficiency into mammalian cells. The cell viability of mouse embryonic
      fibroblasts (MEFs) after the incubation with various concentrations of KRKRWHW
      from 0.01mM to 5mM at 37 degrees C for 4h was maintained at around 100%. The
      peptide was able to penetrate into MEFs within 1h at 37 degrees C with an
      efficiency of around 90% at 0.1mM. Trehalose, as a cargo coupled with the peptide
      of KRKRWHW through hydrogen bond and pi-pi bond, was successfully loaded into the
      MEFs. This novel peptide provides a novel approach for the delivery of trehalose
      into mammalian cells. 

PMID- 24583083
TI  - Membrane disorder and phospholipid scrambling in electropermeabilized and viable
      cells.
AB  - Membrane electropermeabilization relies on the transient permeabilization of the
      plasma membrane of cells submitted to electric pulses. This method is widely used
      in cell biology and medicine due to its efficiency to transfer molecules while
      limiting loss of cell viability. However, very little is known about the
      consequences of membrane electropermeabilization at the molecular and cellular
      levels. Progress in the knowledge of the involved mechanisms is a biophysical
      challenge. As a transient loss of membrane cohesion is associated with membrane
      permeabilization, our main objective was to detect and visualize at the single
      cell level the incidence of phospholipid scrambling and changes in membrane
      order. We performed studies using fluorescence microscopy with C6-NBD-PC and FM1
      43 to monitor phospholipid scrambling and membrane order of mammalian cells.
      Millisecond permeabilizing pulses induced membrane disorganization by increasing
      the translocation of phosphatidylcholines according to an ATP-independent
      process. The pulses induced the formation of long-lived permeant structures that
      were present during membrane resealing, but were not associated with
      phosphatidylcholine internalization. These pulses resulted in a rapid
      phospholipid flip/flop within less than 1s and were exclusively restricted to the
      regions of the permeabilized membrane. Under such electrical conditions,
      phosphatidylserine externalization was not detected. Moreover, this electrically
      mediated membrane disorganization was not correlated with loss of cell viability.
      Our results could support the existence of direct interactions between the
      movement of membrane zwitterionic phospholipids and the electric field. 

PMID- 24583084
TI  - Conformational changes of the histidine ATP-binding cassette transporter studied
      by double electron-electron resonance spectroscopy.
AB  - The conformational dynamics of the histidine ABC transporter HisQMP2 from
      Salmonella enterica serovar Typhimurium, reconstituted into liposomes, is studied
      by site-directed spin labeling and double electron-electron resonance
      spectroscopy in the absence of nucleotides, in the ATP-bound, and in the post
      hydrolysis state. The results show that the inter-dimer distances as measured
      between the Q-loops of HisP2 in the intact transporter resemble those determined
      for the maltose transporter in all three states of the hydrolysis cycle. Only in
      the presence of liganded HisJ the closed conformation of the nucleotide binding
      sites is achieved revealing the transmembrane communication of the presence of
      substrate. Two conformational states can be distinguished for the periplasmic
      moiety of HisQMP2 as detected by differences in distributions of interspin
      distances between positions 86 and 96 or 104 and 197. The observed conformational
      changes are correlated to proposed open, semi-open and closed conformations of
      the nucleotide binding domains HisP2. Our results are in line with a
      rearrangement of transmembrane helices 4 and 4' of HisQM during the closed to the
      semi-open transition of HisP2 driven by the reorientation of the coupled helices
      3a and 3b to occur upon hydrolysis. 

PMID- 24583085
TI  - Insulins, leptin and feeding in a population of Peromyscus leucopus (white-footed
      mouse) with variable fertility.
AB  - This article is part of a Special Issue "Energy Balance". Natural populations
      display a variety of reproductive responses to environmental cues, but the
      underlying physiology that causes these responses is largely unknown. This study
      tested the hypothesis that heritable variation in reproductive traits can be
      described by heritable variation in concentrations of hormones critical to both
      energy balance and reproduction. To test this hypothesis, we used mouse lines
      derived from a wild population and selectively bred for response to short day
      photoperiod. Reproductive and metabolic traits of Peromyscus leucopus display
      heritable variation when held in short photoperiods typical of winter. Our two
      lines of mice have phenotypes spanning the full range of variation observed in
      nature in winter. We tested male and female mice for heritable variation in
      fasted serum concentrations of three hormones involved in energetic regulation:
      leptin, insulin-like growth factor 1 (IGF-1) and insulin, as well as the effects
      of exogenous leptin and a high energy diet on reproductive maturation. Exogenous
      leptin decreased food intake, but protected males from the reduction in testis
      mass caused by equivalent food restriction in pair-fed, saline-infused controls.
      A high energy diet resulted in calorie adjustment by the mice, and failed to
      alter reproductive phenotype. Concentrations of the three hormones did not differ
      significantly between selection lines but had correlations with measures of food
      intake, fertility, blood glucose, and/or body mass. There was evidence of
      interactions between reproductive traits and hormones related to energy balance
      and reproduction, but this study did not find evidence that variation in these
      hormones caused variation in reproductive phenotype. 

PMID- 24583086
TI  - Complication rate in 200 consecutive sinus lift procedures: guidelines for
      prevention and treatment.
AB  - PURPOSE: Maxillary sinus grafting is a predictable and reliable procedure that
      has been routinely performed for more than 30 years. The complication rate is
      low, but some cases may require additional surgery, and the outcome of oral
      rehabilitation may be affected. The purpose of the present study was to evaluate
      the early and late complications after sinus lift procedures performed in the
      authors' center, with special attention to risk factors and their connection to
      the principles of prevention and treatment. MATERIALS AND METHODS: A
      retrospective analysis of 127 patients was performed. During an 8-year period,
      patients underwent preprosthetic surgery with implants and a maxillary sinus lift
      procedure because of maxillary atrophy. In total, 202 sinus lift procedures were
      performed and 364 implants were placed (117 simultaneously and 247 delayed).
      Clinical data, local or systemic disease, risk factors, type of surgery,
      intraoperative and postoperative complications, and the evolution of the implant
      zone were recorded. RESULTS: The most common intraoperative complication was
      damage to the Schneiderian membrane (25.7%), which did not show any connection to
      postoperative complications. Thirty patients (14.9%) developed postoperative
      complications, including wound infection, abscess, or dehiscence with drainage (9
      cases), maxillary sinusitis of the operated area (6 cases), partial exposure of
      the simultaneous onlay graft (6 cases), and loss of the graft (2 cases).
      CONCLUSION: Sinus lift surgery is a proven and reliable technique because of the
      low observed rate of postoperative complications and the success rate of implants
      placed into the grafted area. To minimize risk, care must be taken with all
      technical details and risk factors that can lead to fatality.

PMID- 24583087
TI  - LINGO-1 regulates oligodendrocyte differentiation by inhibiting ErbB2
      translocation and activation in lipid rafts.
AB  - Oligodendrocyte differentiation is negatively regulated by LINGO-1 and positively
      regulated by the ErbB2 receptor tyrosine kinase. In wild-type oligodendrocytes,
      inhibition of ErbB2 blocks differentiation, whereas activation of ErbB2 promotes
      differentiation. In LINGO-1(-/-) oligodendrocytes, inhibition of ErbB2 blocks
      oligodendrocyte differentiation; whereas activation of ErbB2 does not enhance
      differentiation. Biological and biochemical evidence showing that LINGO-1 can
      directly bind to ErbB2, block ErbB2 translocation into lipid rafts, and inhibit
      its phosphorylation for activation. The study demonstrates a novel regulatory
      mechanism of ErbB2 function whereby LINGO-1 suppresses oligodendrocyte
      differentiation by inhibiting ErbB2 translocation and activation in lipid rafts. 

PMID- 24583090
TI  - Post-exercise increment in compound muscle action potential amplitude in
      hyperkalemic periodic paralysis.

PMID- 24583089
TI  - Past strategies and future directions for identifying AMP-activated protein
      kinase (AMPK) modulators.
AB  - AMP-activated protein kinase (AMPK) is a promising therapeutic target for cancer,
      type II diabetes, and other illnesses characterized by abnormal energy
      utilization. During the last decade, numerous labs have published a range of
      methods for identifying novel AMPK modulators. The current understanding of AMPK
      structure and regulation, however, has propelled a paradigm shift in which many
      researchers now consider ADP to be an additional regulatory nucleotide of AMPK.
      How can the AMPK community apply this new understanding of AMPK signaling to
      translational research? Recent insights into AMPK structure, regulation, and
      holoenzyme-sensitive signaling may provide the hindsight needed to clearly
      evaluate the strengths and weaknesses of past AMPK drug discovery efforts.
      Improving future strategies for AMPK drug discovery will require pairing the
      current understanding of AMPK signaling with improved experimental designs. 

PMID- 24583088
TI  - Brain-gut microbiome interactions and functional bowel disorders.
AB  - Alterations in the bidirectional interactions between the intestine and the
      nervous system have important roles in the pathogenesis of irritable bowel
      syndrome (IBS). A body of largely preclinical evidence suggests that the gut
      microbiota can modulate these interactions. A small and poorly defined role for
      dysbiosis in the development of IBS symptoms has been established through
      characterization of altered intestinal microbiota in IBS patients and reported
      improvement of subjective symptoms after its manipulation with prebiotics,
      probiotics, or antibiotics. It remains to be determined whether IBS symptoms are
      caused by alterations in brain signaling from the intestine to the microbiota or
      primary disruption of the microbiota, and whether they are involved in altered
      interactions between the brain and intestine during development. We review the
      potential mechanisms involved in the pathogenesis of IBS in different groups of
      patients. Studies are needed to better characterize alterations to the intestinal
      microbiome in large cohorts of well-phenotyped patients, and to correlate
      intestinal metabolites with specific abnormalities in gut-brain interactions.

PMID- 24583091
TI  - Experimental observation of a theoretically predicted nonlinear sleep spindle
      harmonic in human EEG.
AB  - OBJECTIVE: To investigate the properties of a sleep spindle harmonic oscillation
      previously predicted by a theoretical neural field model of the brain. METHODS:
      Spindle oscillations were extracted from EEG data from nine subjects using an
      automated algorithm. The power and frequency of the spindle oscillation and the
      harmonic oscillation were compared across subjects. The bicoherence of the EEG
      was calculated to identify nonlinear coupling. RESULTS: All subjects displayed a
      spindle harmonic at almost exactly twice the frequency of the spindle. The power
      of the harmonic scaled nonlinearly with that of the spindle peak, consistent with
      model predictions. Bicoherence was observed at the spindle frequency, confirming
      the nonlinear origin of the harmonic oscillation. CONCLUSIONS: The properties of
      the sleep spindle harmonic were consistent with the theoretical modeling of the
      sleep spindle harmonic as a nonlinear phenomenon. SIGNIFICANCE: Most models of
      sleep spindle generation are unable to produce a spindle harmonic oscillation, so
      the observation and theoretical explanation of the harmonic is a significant step
      in understanding the mechanisms of sleep spindle generation. Unlike seizures,
      sleep spindles produce nonlinear effects that can be observed in healthy
      controls, and unlike the alpha oscillation, there is no linearly generated
      harmonic that can obscure nonlinear effects. This makes the spindle harmonic a
      good candidate for future investigation of nonlinearity in the brain.

PMID- 24583092
TI  - Photodynamic therapy versus ultrasonic irrigation: interaction with endodontic
      microbial biofilm, an ex vivo study.
AB  - INTRODUCTION: Photodynamic therapy was introduced as an adjuvant to conventional
      chemo-mechanical debridement during endodontic treatment to overcome the
      persistence of biofilms. The aim of this study was to evaluate the ability of
      photodynamic therapy (PDT) to disrupt an experimental microbial biofilm inside
      the root canal in a clinically applicable working time. MATERIALS AND METHODS:
      Thirty extracted teeth were prepared and then divided in three groups. All
      samples were infected with an artificially formed biofilm made of Enterococcus
      faecalis, Streptococcus salivarius, Porphyromonas gingivalis and Prevotella
      intermedia bacteria. First group was treated with Aseptim Plus(r) photo-activated
      (LED) disinfection system, second group by a 650 nm Diode Laser and Toluidine
      blue as photosensitizer, and the third group, as control group, by ultrasonic
      irrigation (PUI) using EDTA 17% and NaOCl 2.6% solutions. The working time for
      all three groups was fixed at 3 min. Presence or absence of biofilm was assessed
      by aerobic and anaerobic cultures. RESULTS: There was no statistically
      significant difference between results obtained from groups treated by Aseptim
      Plus(r) and Diode Laser (P<0.6267). In cultures of both groups there was a
      maximal bacterial growth. The group that was treated by ultrasonic irrigation and
      NaOCl and EDTA solutions had the best results (P<0.0001): there was a
      statistically significant reduction of bacterial load and destruction of
      microbial biofilm. CONCLUSION: Under the condition of this study, Photodynamic
      therapy could not disrupt endodontic artificial microbial biofilm and could not
      inhibit bacterial growth in a clinically favorable working time.

PMID- 24583093
TI  - Severe acute airway obstruction and respiratory failure with fibrous plug
      following photodynamic therapy (PDT): indication for early bronchoscopy and
      debridement.
AB  - INTRODUCTION: PDT is a safe procedure with most post procedural complications
      reported as minor. We report a case of severe acute stridor and trachea-bronchial
      airway obstruction with mucosal sloughing and fibrous plugs resulting in
      respiratory failure within three hours following PDT. To our knowledge this is
      the first reported case where stridor and acute respiratory failure resulted
      within hours following PDT treatment. CASE REPORT: A 65 year old female with
      previous right pneumonectomy presented with followup bronchoscopy confirming
      reoccurrence of carcinoma proximal and distal to the anastomosis. A standard
      photofrin (Porfimer sodium) was administered at 2mg/kg body weight 48 hours prior
      to her PDT treatment. Three hours following the procedure, patient become acutely
      stridurous and was subsequently intubated. Bedside bronchoscopy was performed
      through the endotracheal tube. During the bronchoscopy thick tracheal plugs were
      retrieved and slough adjacent to the treatment site was noticed which was
      debrided. Patient underwent 7 bronchoscopies with debridement before she was
      discharged. CONCLUSION: Airway obstruction (with NSCLA) is an indication as well
      as complication (with mucosal debris) of PDT. FDA has advised bronchoscopy at 48
      72 hours post procedure, however early intervention with bronchoscopy and
      debridement should be considered to relieve tracheal bronchial airway obstruction
      and removal of accessory debris and mucosal slough.

PMID- 24583094
TI  - An antilisterial bacteriocin BacFL31 produced by Enterococcus faecium FL31 with a
      novel structure containing hydroxyproline residues.
AB  - A new bacterium called FL31, which was selected for its antimicrobial activity
      against the pathogenic bacterium Listeria monocytogenes, was identified as
      Enterococcus faecium and noted to produce an antibacterial proteinaceous
      substance (BacFL31). The active peptide from the cell-free supernatant of E.
      faecium FL31 was purified in four steps and the results revealed a single band
      with an estimated molecular mass of approximately 3.5 kDa. The N-terminal amino
      acid sequence of the purified BacFL31 "GLEESXGHXGQXGPXGPXGAXGP" (X =
      hydroxyproline) showed the presence of six hydroxyproline residues. It displayed
      a bactericidal mode of action against L. monocytogenes. Its application at 400
      AU/g was also noted to constitute an effective approach for preventing the
      contamination and growth of the pathogenic bacterium L. monocytogenes during the
      storage of minced beef meat at 4  degrees C. 

PMID- 24583095
TI  - Effects of single- and multi-strain probiotics on biofilm formation and in vitro
      adhesion to bladder cells by urinary tract pathogens.
AB  - PURPOSE: There is increasing evidence that probiotic bacteria can inhibit and/or
      prevent urinary tract infections. Possible mechanisms include prevention of
      adhesion of pathogens to the bladder epithelium and inhibition of biofilm
      formation. Currently there is interest in the comparative efficacy of single
      probiotics vs. strain mixtures. We have therefore tested the inhibitory activity
      of four single probiotics and four probiotic mixtures towards the urinary tract
      pathogens Escherichia coli NCTC 9001 and Enterococcus faecalis NCTC 00775.
      METHODS: Inhibition of biofilm formation by cell-free supernatants was tested
      using the Crystal Violet assay, while prevention of pathogen adhesion to host
      cells was tested by using bladder cancer cells as a model for the human urinary
      tract. RESULTS: Under pH-controlled conditions, there was no significant
      inhibition of biofilm formation by any treatment. Without pH control, 5/8
      treatments significantly inhibited biofilm production by E. coli, while 5/8
      treatments inhibited production by E. faecalis. Using data from all Crystal
      Violet assays, there was no significant difference in the ability of single- and
      multi-strain probiotics to inhibit biofilm formation. In the cell culture assays,
      all treatments were able to significantly reduce numbers of pathogenic cells
      adhering to host cells by 2.5-3.5 logs. No significant difference was observed
      between the displacement caused by single strains and mixtures for either
      pathogen. CONCLUSIONS: Inhibition of biofilm seems to be a major mechanism of
      urinary tract pathogen exclusion, related to, and possibly dependent upon, the
      probiotic ability to reduce environmental pH. Exclusion via competition of
      binding sites is a possible in vivo mechanism for these probiotics. If an
      additive or synergistic effect exists between strains within a mixture, it does
      not manifest itself in a greater effect through these two inhibitory mechanisms.

PMID- 24583096
TI  - Early and long-term results after reconstructive surgery in 42 children and two
      young adults with renovascular hypertension due to fibromuscular dysplasia and
      middle aortic syndrome.
AB  - OBJECTIVES: This retrospective study presents the early and late results of
      pediatric patients who underwent reconstructive surgery for renovascular
      hypertension (RVH) between 1979 and 2009. METHODS: From 1979 to 2009 44 patients
      (male 22; mean age 13+/-5.2 years, range 1-19 years; early childhood 7 [1-6
      years], middle childhood 5 [7-10 years]; adolescents 32 [11-19 years]) with
      renovascular hypertension underwent surgery for abdominal aortic stenoses (n=6),
      renal artery stenosis (RAS) (n=25) or for combined lesions (n=13). Nineteen
      aortic stenoses (bypass/interposition 10/5, patch
      dilatation/thromboendarterectomy 2/2), 51 renal arteries (interposition 36,
      resection+reimplantation 13, patch dilatation/aneurysmorraphy 1 each), and 10
      visceral arteries (resection+reimplantation 6, interposition 3, patch dilatation
      1) were reconstructed. Each patient underwent duplex studies and if required
      intra-arterial digital subtraction angiography. Reoperations within 30
      postoperative days were required in four (9%) of the patients for occlusion of
      four arteries (6%), achieving a combined technical success rate of 94%. RESULTS:
      After 114+/-81 months 36 patients were re-examined by duplex and magnetic
      resonance angiography (2 not surgery-related deaths 7/12 years postoperatively, 8
      patients lived abroad). Twelve patients had required a second and three a third
      procedure. Hypertension was cured early/late postoperatively in 27%/56%, improved
      in 41%/44%, and remained unchanged in 32%/0%. Best late results were obtained in
      patients with isolated aortic disease and at the age of middle childhood.
      CONCLUSIONS: Reconstructive surgery for pediatric RVH yields good results at
      every age and every type of lesion. However, these children should be followed up
      closely and to avoid early cardiovascular disease and death in later life,
      surgery should not be delayed.

PMID- 24583098
TI  - Radiofrequency ablation annotation algorithm reduces the incidence of linear gaps
      and reconnection after pulmonary vein isolation.
AB  - BACKGROUND: A common mechanism of atrial fibrillation recurrence after catheter
      ablation is resumption of pulmonary vein (PV) conduction due to gaps in the
      ablation line. These gaps may go unrecognized owing to inadequate ablation lesion
      annotation. OBJECTIVE: To examine the utility of an automated radiofrequency (RF)
      ablation annotation algorithm for the detection and treatment of ablation gaps
      during pulmonary vein isolation (PVI). METHODS: Eighty-four patients with
      paroxysmal atrial fibrillation underwent PVI. In 42 patients (group A), RF
      ablation was guided by an automated algorithm with predefined criteria of
      catheter stability range of motion <=2 mm and impedance decrease >=5% for
      individual ablation applications. In 42 control patients (group B), ablation was
      guided by the operator. Successful PVI, conduction recovery, and dormant
      conduction with adenosine were compared between the groups. RESULTS: Ipsilateral
      PVI at the completion of the initial anatomical line was obtained in 90.5% of
      group A patients (76 of 84 ipsilateral pairs of PVs) but only in 66.7% of group B
      patients (56 of 84 ipsilateral pairs of PVs) (P = .0001). Ineffective energy
      delivery was detected in 23% (1005 of 4362) of group A applications but only in
      9% (368 of 4071) of group B applications (P = .0001). The frequency of conduction
      recovery was lower in group A than in group B (5.9% vs 25%; P = .001). Arrhythmia
      free survival at 6 months trended higher in group A (38 of 42 [90%]) than in
      group B (32 of 42 [76%]; P = .07). CONCLUSION: Automated ablation lesion
      annotation provides real-time feedback of RF ablation that may improve effective
      energy delivery.

PMID- 24583099
TI  - Structural model of factors influencing smoking behavior among Korean-Chinese
      adolescent boys.
AB  - AIM: The aim of this study is to develop and test structural equation model to
      explore factors influencing smoking behavior among Korean-Chinese adolescent
      boys. METHODS: Participants were recruited from six middle schools in China
      (N=768). Self-administered questionnaire included: (1) demographic information,
      (2) smoking behavior, and (3) individual factor (i.e., life satisfaction, future
      orientedness, stress), familial factor (i.e., relationship with parents, family
      life, socioeconomic status), environmental factor (i.e., father's smoking,
      friends' smoking, anti-smoking environment), and Intention Refusal Self-efficacy.
      AMOS analyses were used to evaluate the proposed model. RESULTS: The model was a
      good fit for the data. Intention Refusal Self-efficacy significantly influenced
      smoking behavior. The model explained 52% of the variance in smoking behavior.
      CONCLUSIONS: Smoking behavior is significantly related with factors of intention
      to smoke, refusal skill, self-efficacy, friends' and father's smoking, and anti
      smoking environment. Targeting these issues might be useful when developing
      strategies for smoking prevention programs.

PMID- 24583097
TI  - Adenosine sensitivity of retrograde fast pathway conduction in patients with slow
      fast atrioventricular nodal reentrant tachycardia: a prospective study.
AB  - BACKGROUND: It is suggested that the adenosine resistance of retrograde fast
      pathway in slow-fast atrioventricular nodal reentrant tachycardia (AVNRT)
      confirms the participation of a concealed retrograde atrio-Hisian pathway rather
      than the conventional fast pathway in the arrhythmia circuit of slow-fast AVNRT.
      OBJECTIVE: To prospectively assess the retrograde fast pathway response to the
      intravenous administration of adenosine in patients with typical AVNRT and the
      control group. METHODS: Electrophysiological parameters and adenosine sensitivity
      of retrograde fast pathway were studied in 21 consecutive patients (18 women;
      mean age 57 +/- 10 years) with slow-fast AVNRT and 24 patients (11 women; mean
      age 46 +/- 16 years) as the control group. RESULTS: Fifteen (71%) patients with
      AVNRT and 18 (75%) patients in the control group developed transient
      ventriculoatrial (VA) block after the intravenous administration of adenosine (P
      = .79). In patients with slow-fast AVNRT, female sex (P = .003), longer VA
      interval during right ventricular pacing (P < .001), and longer tachycardia cycle
      length (P < .001) predicted transient VA block after the intravenous
      administration of adenosine. In patients in the control group, a shorter VA
      interval during fixed rate right ventricular apical pacing (P = .009) and the
      presence of dual atrioventricular nodal physiology (P = .002) were associated
      with the adenosine resistance of the retrograde fast pathway. CONCLUSIONS: The
      prevalence of the adenosine resistance of retrograde fast pathway's conduction is
      comparable between patients with and those without slow-fast AVNRT. This finding
      can be explained better by the existence of an insulated intranodal tract with
      Purkinje-like properties or a superior atrionodal connection to the nodo-Hisian
      region of the atrioventricular node rather than the presence of an atrio-Hisian
      pathway.

PMID- 24583100
TI  - Cellular functions of the dual-targeted catalytic subunit of telomerase,
      telomerase reverse transcriptase--potential role in senescence and aging.
AB  - Over the last 40 years it has become clear that telomeres, the end of the
      chromosomes, and the enzyme telomerase reverse transcriptase (TERT), which is
      required to counteract their shortening, play a pivotal role in senescence and
      aging. However, over the last years several studies demonstrated that TERT
      belongs to the group of dual-targeted proteins. It contains a bipartite nuclear
      localization signal as well as a mitochondrial targeting sequence and, under
      physiological conditions, is found in both organelles in several cell types
      including terminally differentiated, post-mitotic cells. The canonical function
      of TERT is to prevent telomere erosion and thereby the development of replicative
      senescence and genetic instability. Besides telomere extension, TERT exhibits
      other non-telomeric activities such as cell cycle regulation, modulation of
      cellular signaling and gene expression, augmentation of proliferative lifespan as
      well as DNA damage responses. Mitochondrial TERT is able to reduce reactive
      oxygen species, mitochondrial DNA damage and apoptosis. Because of the
      localization of TERT in the nucleus and in the mitochondria, it must have
      different functions in the two organelles as mitochondrial DNA does not contain
      telomeric structures. However, the organelle-specific functions are not
      completely understood. Strikingly, the regulation by phosphorylation of TERT
      seems to reveal multiple parallels. This review will summarize the current
      knowledge about the cellular functions and post-translational regulation of the
      dual-targeted protein TERT.

PMID- 24583101
TI  - Brief stimuli as context.
AB  - Context may be defined as a stimulus that provides global information about the
      reinforcement rate in the current environment. Twenty-four rats were trained in
      lever boxes with different stimuli serving as context on different sessions. The
      goal of the first experiment was to determine whether or not brief stimuli
      provide global information as effectively as continuous stimuli. The sessions
      contained brief stimuli at random times throughout the sessions, a continuous
      stimulus throughout the session, both brief and continuous stimuli, or neither.
      Results indicated that brief and continuous stimuli provided similar global
      information (i.e., they served as contextual stimuli). The goal of the second
      experiment was to determine the differential effects brief stimuli have on
      behavior when they provide either global or local information. The conclusion was
      that stimuli that provide local information regarding the time of reinforcement
      affect the time of responses, and that stimuli that provide global information
      affect response rate. This article is part of a Special Issue entitled: insert SI
      title. 

PMID- 24583102
TI  - Consensus analysis of sastric formulations used by non-institutionally trained
      siddha medical practitioners of Virudhunagar and Tirunelveli districts of Tamil
      Nadu, India.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Siddha system of traditional medicine has been
      practiced in Tamil Nadu. This system of medicine has a high number of non
      institutionally trained practitioners but studies on their traditional medicinal
      knowledge are not adequate. The present study is aimed to document and analyze
      the sastric (traditional) formulations used by the non-institutionally trained
      siddha medical practitioners in Virudhunagar and Tirunelveli districts of Tamil
      Nadu, India. METHODS: After obtaining prior informed consent, interviews were
      conducted with 115 non-institutionally trained siddha medical practitioners about
      the sastric formulations used by them for the treatment. Successive free listing
      method was adopted to collect the data and the data were analyzed by calculating
      Informant Consensus Factor (Fic) and Informant Agreement Ratio (IAR). RESULTS:
      The study documented data regarding 194 sastric formulations and they were
      classified into plant, mineral and animal based formulations. Quantitative
      analysis showed that 62.5% of the formulations were plant based, while the
      mineral based formulations had a high mean number of citations and versatile
      uses. Gastrointestinal (12.0%), kapha (11.3%) and dermatological (10.8%) ailments
      had a high percentage of citations. Jaundice had a high Fic value (0.750)
      followed by the dermatological ailments. The illness categories with high Fic
      values under each type of formulation were as follows: jaundice, aphrodisiac and
      urinary ailments (plant based); jaundice, cuts & wounds and dermatological
      ailments (mineral based); and hemorrhoids, kapha ailments and heart ailments
      (animal based formulations). The scientific studies conducted with important
      formulations under each illness category are discussed. CONCLUSION: The present
      study indicated the importance of some illnesses over the others and inclusion of
      new illnesses under each formulation. The ingredients used to prepare these
      formulations have shown varying degrees of scientific evidence; generally limited
      studies were available on the efficacy of them as formulations. Further in-depth
      studies on the formulations with high IAR value and Fic value of illness
      categories will be helpful to improve health status of the people.

PMID- 24583103
TI  - Therapeutic effects of dichloromethane fraction of Securidaca inappendiculata on
      adjuvant-induced arthritis in rat.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Securidaca inappendiculata (SI) is a traditional
      antirheumatic medicine used in China. The present study was designed to
      investigate the therapeutic efficacy of dichloromethane fraction of SI (SID) at
      three different doses on adjuvant induced arthritis (AA) rats. METHODS: Arthritis
      severity was evaluated by arthritic score, body weight loss, paw circumference,
      histological changes and hyperplasia of lymphatic tissues. Serum samples were
      collected for estimation of superoxide dismutase (SOD), glutathione (GSH),
      hydroxy radical (OH.), nitric oxide (NO), malondialdehyde (MDA), N-acetyl
      glucosaminidase (NAG), sialic acid (SA), alkaline phosphatase (ALP), aspartate
      transaminase (AST) and alanine transaminase (ALT). The levels of GSH, MDA, NAG
      and SA in liver were also assessed. The levels of interleukin-1 (IL-1), tumor
      necrosis factor alpha (TNF-alpha), monocyte chemotactic protein 1 (MCP-1) and
      vascular endothelial growth factor (VEGF) were determined using ELISA method.
      Another portion of blood was used for total and differential leucocyte counts.
      RESULTS: Administration with SID (at high dose with 100 mg/kg) significantly
      ameliorated the AA severity, suggested by the modulatory effects on body weight
      loss, paw swelling, hyperplasia of lymphatic tissues and synovial membrane,
      neutrocytosis and lymphocytosis. It also decreased levels of NO, MDA and OH.,
      restored SOD and GSH levels in serum. The abnormal increased levels of AST, ALT,
      ALP, NAG and SA significantly were reverted (compared with AA rats, P<0.01). A
      similar result was observed in livers. Levels of IL-1, TNF-alpha, MCP-1 and VEGF
      were reduced dramatically by SID too. CONCLUSION: The results suggest SID
      possesses substantial anti-arthritic activity. The therapeutic efficacy may be
      due to immumodepressive effects, cytokines regulation, increasing membrane
      stability and antioxidantive activity.

PMID- 24583104
TI  - Pharmacological basis for the medicinal use of Carissa carandas in constipation
      and diarrhea.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Carissa carandas Linn. commonly known as
      "Karaunda" (Apocynaceae) is a popular medicinal herb widely distributed in
      different parts of Pakistan. In addition to other medicinal uses, Carissa
      carandas is popular in indigenous system of medicine for its medicinal use in gut
      motility disorders like, constipation and diarrhea. OBJECTIVE: This study was
      planned to provide pharmacological basis to the medicinal use of Carissa carandas
      in constipation and diarrhea. MATERIALS AND METHODS: The crude extract of the
      leaves of Carissa carandas (Cc.Cr) was prepared in methanol and its fractionation
      was carried out with ethylacetate, petroleum ether and n-butanol. In-vivo studies
      were conducted on mice, while isolated rabbit jejunum and guinea-pig ileum
      preparations were used for the in-vitro experiments. The spasmogenic and
      spasmolytic responses of gut tissues were recorded using isotonic transducers
      coupled with PowerLab data acquisition system. RESULTS: The HPLC fingerprints of
      Cc.Cr, its petroleum (Cc.Pef), ethylacetate (Cc.Eaf) and n-butanol (Cc.Baf)
      fractions showed the presence of oleanolic acid, ursolic acid, stigmasterol and
      beta-sitosterol. Oral administration of Cc.Cr to mice increased fecal output at
      lower doses (30 and 50 mg/kg), while it showed protection against castor oil
      induced diarrhea at higher doses (300 and 600 mg/kg). In isolated guinea-pig
      ileum and rabbit jejunum, Cc.Cr and Cc.Baf exhibited stimulatory effect at 0.003
      3 mg/ml, which was partially sensitive to atropine or pyrillamine or
      partially/fully sensitive to atropine+pyrillamine, followed by relaxation at
      higher tested concentrations, being more potent in rabbit tissues. The
      ethylacetate fraction (0.1-5 mg/ml) exhibited fully atropine-sensitive
      contractions in both guinea-pig and rabbit tissues, being more potent in guinea
      pig while more efficacious in rabbit tissues. However, the petroleum fraction
      (0.003-1.0 mg/ml) showed only spasmolytic activity in spontaneously contracting
      rabbit tissues, similar to nifedipine. In guinea-tissue, Cc.Pef did not cause any
      stimulant effect. When studied against high K(+) (80 mM)-induced contraction, the
      crude extract and its fractions caused a dose-dependent inhibition, with the
      following order of potency: Cc.Pef>Cc.Eaf>Cc.Cr>=Cc.Baf, similar to nifedipine
      indicating Ca(++) channel antagonist like activity, which was further confirmed
      when the plant extract displaced Ca(++) curves to the right with suppression of
      maximum effect similar to that of nifedipine. CONCLUSION: This study demonstrates
      that the crude extract of Carissa carandas possesses a gut-stimulatory effect
      mediated primarily through the activation of muscarinic and histaminergic
      receptors while its spasmolytic effect was mediated possibly through Ca(++)
      antagonist pathway. Thus, this study provides a clear evidence for the dual
      effectiveness of Carissa carandas in constipation and diarrhea, thus validating
      its medicinal use.

PMID- 24583105
TI  - Topical continuous use of Lippia sidoides Cham. essential oil induces cutaneous
      inflammatory response, but does not delay wound healing process.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The essential oil of Lippia sidoides (EOLS) has
      been used in Brazilian folk medicine as a topical antiseptic agent in skin for
      treatment of wounds and superficial infections of the body. The aim of this study
      was to investigate the effects of EOLS on intact and damaged skin, including its
      action on expression of mediators, COX-2 and VEGF, involved in healing full
      thickness cutaneous lesions in vivo. MATERIAL AND METHODS: EOLS was analyzed
      chemically and used at different concentrations to dose-response experiments in
      skin mice. Skin irritation tests by one-dosage and multiple-dosages and
      irritation to damaged skin were assessed by macroscopy, morphometry and
      histological and immunohistochemical analyses. To evaluate the effects of EOLS on
      wound healing, excision wounds were surgically created on the dorsum of rats, and
      the ointments at 6% and 12% were applied daily to the wound area. Cutaneous
      lesions were assessed by planimetric (wound contraction) and macroscopic
      parameters. RESULTS: Skin irritation tests showed that topical application of
      EOLS promoted cutaneous inflammation in varying degrees, which was demonstrated
      by increase of skin thickness and formation of cutaneous edema and erythema.
      Topical administration of EOLS in high concentrations presented an irritant
      response to skin, but this irritation is lighter when low concentrations this oil
      were used. Histological evaluation supported the outcome of these models, which
      revealed accentuated presence of inflammatory cells infiltration. In wound
      healing process, the lesions treated with EOLS showed intense edema and
      exsudation up to day 5, but there were not significant differences in the wound
      contraction on days 14 and 21. No immunohistochemical staining was verified to
      COX-2 and VEGF mediators in skin treated with EOLS 12%. CONCLUSION: The
      continuous application of EOLS in adequate concentrations on cutaneous wounds
      increases inflammatory response without delay the lesions closure. The
      association of these results with antimicrobial action previously related to EOLS
      allows its indication as an alternative therapeutic modality for topical
      treatment of infected cutaneous wound. Nevertheless, further studies need to be
      performed to determine the mechanism of action and support its application in
      clinical practice.

PMID- 24583106
TI  - Use of medicinal plants in the South-Eastern area of the Partenio Regional Park
      (Campania, Southern Italy).
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: This study documents the pharmaceutical
      importance of plant resources in the South-Eastern area of the Partenio Regional
      Park (PRP), inland Campania, Avellino province. This is reflected in the great
      diversity of plants used for medicinal purposes as well as in their wide range of
      medicinal applications. MATERIALS AND METHODS: In order to collect information on
      medicinal plants used in the investigated area and to maximize the collection of
      local knowledge, informants were randomly contacted in the streets, squares and
      fields. Data were collected through both open and semi-structured interviews with
      native people between April 2012 and April 2013. RESULTS: The study recorded 87
      plant species belonging to 76 genera and 35 families used as medicine for
      treating various diseases, both human and veterinary. Herbs represent the
      majority (56 species), followed by trees (18) and shrubs (13). Among the recorded
      plants, leaves were the most frequently used and topic use is the most common
      remedy. Cough is the most treated human disease followed by wounds healing.
      CONCLUSION: The investigated area is endowed with a strong tradition of herbal
      medicine usage for primary healthcare (PHC). The preservation of this knowledge
      is due to the continued use of plants for PHC by the local community. This is due
      to the fact that in the study area still exists an oral tradition that allows the
      persistence of such information. Recovering ancient knowledge is very important
      for preserving ethno-biodiversity and to discover new entities for a further
      evaluation of their biological activity.

PMID- 24583107
TI  - Antihypertensive activities of the aqueous extract of Kalanchoe pinnata
      (Crassulaceae) in high salt-loaded rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The leaves of Kalanchoe pinnata (Crassulaceae)
      are used in Cameroon folk medicine to manage many diseases such as cardiovascular
      dysfunctions. In this work, we aimed to evaluate the activities of aqueous leaf
      extract of Kalanchoe pinnata on the blood pressure of normotensive rat (NTR) and
      salt hypertensive rats (SHR), as well as its antioxidant properties. MATERIALS
      AND METHODS: Hypertension was induced in rats by oral administration of 18% NaCl
      for 4 weeks. For the preventive study, three groups of rats received 18% NaCl
      solution and the plant extract at 25 mg/kg/day, 50 mg/kg/day or 100 mg/kg/day by
      gavage. Two positive control groups received 18% NaCl solution and either
      spironolactone (0.71 mg/kg/day) or eupressyl (0.86 mg/kg/day) by gavage for 4
      weeks. At the end of this experimental period, systolic arterial pressure (SAP),
      diastolic arterial pressure (DAP) and heart rate (HR) were measured by the
      invasive method. Some oxidative stress biomarkers (reduced glutathione (GSH),
      superoxide dismutase (SOD), nitric monoxide (NO) were evaluated in heart, aorta,
      liver and kidney. NO level was indirectly evaluated by measuring nitrite
      concentration. RESULTS: Kalanchoe pinnata extract prevented significantly the
      increase of systolic and diastolic arterial pressures in high salt-loaded rats
      (SHR). In SHR, concomitant administration of Kalanchoe pinnata at 25, 50 and 100
      mg/kg/day significantly prevented the increase in blood pressure by 32%, 24% and
      47% (for SAP); 35%, 33% and 56% (for DAP), respectively. No significant change
      was recorded in heart rate of those rats. The plant extract improved antioxidant
      status in various organs, but more potently in aorta. Thus, antioxidant and
      modulatory effects of Kalanchoe pinnata at the vasculature might be of
      preponderant contribution to its overall antihypertensive activity. CONCLUSION:
      The work demonstrated that the concomitant administration of high-salt and the
      aqueous extract of Kalanchoe pinnata elicits prevention of salt-induced
      hypertension in rat. This antihypertensive activity is associated with an
      improvement of antioxidant status. Overall, results justify and support the use
      of Kalanchoe pinnata as antihypertensive medicine.

PMID- 24583108
TI  - Anti-diabetic effects of the acetone fraction of Senna singueana stem bark in a
      type 2 diabetes rat model.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Senna singueana is currently used in the
      traditional treatment of diabetes mellitus in Nigeria. The present study examined
      the anti-diabetic activity of the Senna singueana acetone fraction (SSAF) of stem
      bark in a type 2 diabetes (T2D) rat model. MATERIALS AND METHODS: Crude ethyl
      acetate extract of the Senna singueana stem bark was fractionated with various
      solvents and the acetone fraction was selected for in vivo studies based on the
      high alpha-glucosidase and alpha-amylase inhibitory activities. In the in vivo
      study, male Sprague-Dawley rats were induced with T2D and treated with the SSAF
      at 150 and 300 mg/kg body weight. Several T2D-related parameters were measured in
      the study. RESULTS: After 4 weeks of intervention, non-fasting blood glucose
      concentrations were significantly decreased and the glucose tolerance ability was
      significantly improved in the SSAF treated groups compared to the diabetic
      control group. Serum insulin concentrations, pancreatic beta-cell function (HOMA
      beta) and liver glycogen were significantly (P<0.05) increased while serum
      alanine transaminase, alkaline phosphatase and urea were significantly decreased
      in the SSAF treated diabetic rats compared to the diabetic control group. Though
      insignificantly (P>0.05), other T2D-induced abnormalities such as food and fluid
      intake, body weight, serum lipids, serum fructosamine level and peripheral
      insulin resistance (HOMA-IR) were also partially ameliorated by the SSAF
      treatment. CONCLUSION: Data of this study suggest that orally administered SSAF
      could ameliorate most of the T2D-induced abnormalities in a T2D model of rats.

PMID- 24583109
TI  - Human papillomavirus detection and genotyping, by HC2, full-spectrum HPV and
      molecular beacon real-time HPV assay in an Irish colposcopy clinic.
AB  - Cervical screening programmes are moving towards HPV testing as part of the
      screening process and as a triage for colposcopy. Three HPV detection methods
      were evaluated using cervical cytology specimens from colposcopy patients.
      PreservCytTM liquid based cytology specimens from 241 women attending colposcopy
      clinics with greater than 2 persistently abnormal smears were recruited through
      the Coombe Women and Infants University Hospital, Dublin. HPV DNA was detected by
      Hybrid Capture (HC2) for 13 high-risk HPV types, Full-Spectrum HPV (FS-HPV) for
      49 high and low-risk types and Molecular Beacon Real-Time HPV assay (MBRT-HPV)
      for 16 high and low-risk types. HPV genotyping was performed using Linear Array
      HPV Assay (LA-HPV). HPV was detected in 83.3% (195/234), 91.9% (217/236) and
      80.1% (169/211) of cytology specimens by HC2, FS-HPV and MBRT-HPV, HPV DNA
      detection assays. The sensitivity of the assays for the detection of high-risk
      HPV in cytology specimens that had a Cervical Intraepithelial Neoplasia Grade 2+
      result by histology were, 98%, 97% and 94% for HC2, FS-HPV and MBRT-HPV assays
      with positive predictive values of 94.1%, 94.1% and 97.3%. The most common HPV
      genotypes were HPV 16, 31, 33, 58, 42, 61 and 53, and the most common high-risk
      HPV genotypes were HPV 16, 31, 33, 58, 18, 45, 59, 51, 56 and 39, with detection
      of multiple infections in 57.7% of all cases. FS-HPV and MBRT-HPV are highly
      sensitive and have a similarly high PPV as the HC2 assay for detection of HPV in
      patients with Cervical Intraepithelial Neoplasia Grade 2+ disease. HPV genotyping
      of women with persistent abnormalities is warranted prior to the introduction of
      HPV DNA testing in a colposcopy setting.

PMID- 24583110
TI  - Generation of a human hepatoma cell line supporting efficient replication of a
      lamivudine resistant hepatitis B virus.
AB  - Emergence of lamivudine (LAM) resistance causes treatment failure in patients
      with chronic hepatitis B and compromise the efficacy of subsequent salvage
      therapies with other nucleot(s)ide analogs (NAs). Establishment of cell-based
      assays supporting LAM-resistant hepatitis B virus (HBV) replication will not only
      provide tools for investigating the replication property, but also screening for
      antiviral agents efficiently inhibiting the replication of LAM-resistant HBV
      variants. Accordingly, a human hepatoma (HepG2)-derived cell line was established
      by stable transfection of a plasmid containing a 1.2 unit length of HBV genome
      harboring rtL180M and rtM204V mutations that confer LAM resistance. In addition
      to support efficient viral genome replication, the cell line also produces high
      levels of HBV virions and subviral particles. As expected, HBV DNA replication in
      this cell line is completely resistant to lamivudine, but sensitive to adefovir
      (ADV), entecavir (ETV) and tenofovir (TDF). The cell line is suitable for
      screening for antiviral agents that inhibit LAM-resistant HBV replication and
      inhibitors of HBsAg biosynthesis and secretion, which may reduce HBsAg
      antigenemia and ultimately help to restore host antiviral immune response against
      HBV and cure chronic HBV infection. 

PMID- 24583111
TI  - Enhancing a search for traditional medicinal plants with anthelmintic action by
      using wild type and stress reporter Caenorhabditis elegans strains as screening
      tools.
AB  - Traditional healers in Sarawak, Malaysia, use plants such as Picria fel-terrae,
      Linariantha bicolor and Lansium domesticum to treat gastrointestinal infections.
      This study aimed to test whether their nematocidal activities could be confirmed
      in vitro using highly standardised Caenorhabditis elegans models. We applied
      eight different ethanol solubilised plant extracts and two commercial
      anthelmintic drugs to larval and adult stages of C. elegans in vitro. Seven C.
      elegans strains were evaluated, one wild type and six strains with GFP-tagged
      stress response pathways to help characterise and compare the pathways affected
      by plant extracts. Our in vitro screen confirmed that both of the commercial
      anthelmintic drugs and five of the eight traditionally used plant extracts had
      significant nematocidal activity against both larval and adult C. elegans. The
      most effective extracts were from P. fel-terrae. The plant extracts triggered
      different stress response pathways from the commercial anthelmintic drugs. This
      study showed that using traditional knowledge of plant medicinal properties in
      combination with a C. elegans in vitro screen provided a rapid and economical
      test with a high hit rate compared with the random screening of plants for
      nematocidal activities. The use of transgenic C. elegans strains may allow this
      approach to be refined further to investigate the mode of action of active
      extracts. 

PMID- 24583112
TI  - Apicoplast acetyl Co-A carboxylase of the human malaria parasite is not targeted
      by cyclohexanedione herbicides.
AB  - Malaria parasites retain a relict plastid (apicoplast) from a photosynthetic
      ancestor. The apicoplast is a useful drug target but the specificity of compounds
      believed to target apicoplast fatty acid biosynthesis has become uncertain, as
      this pathway is not essential in blood stages of the parasite. Herbicides that
      inhibit the plastid acetyl Coenzyme A (Co-A) carboxylase of plants also kill
      Plasmodium falciparum in vitro, but their mode of action remains undefined. We
      characterised the gene for acetyl Co-A carboxylase in P. falciparum. The P.
      falciparum acetyl-CoA carboxylase gene product is expressed in blood stage
      parasites and accumulates in the apicoplast. Ablation of the gene did not render
      parasites insensitive to herbicides, suggesting that these compounds are acting
      off-target in blood stages of P. falciparum. 

PMID- 24583113
TI  - Chemical mutagens, transposons, and transgenes to interrogate gene function in
      Drosophila melanogaster.
AB  - The study of genetics, genes, and chromosomal inheritance was initiated by Thomas
      Morgan in 1910, when the first visible mutations were identified in fruit flies.
      The field expanded upon the work initiated by Herman Muller in 1926 when he used
      X-rays to develop the first balancer chromosomes. Today, balancers are still
      invaluable to maintain mutations and transgenes but the arsenal of tools has
      expanded vastly and numerous new methods have been developed, many relying on the
      availability of the genome sequence and transposable elements. Forward genetic
      screens based on chemical mutagenesis or transposable elements have resulted in
      the unbiased identification of many novel players involved in processes probed by
      specific phenotypic assays. Reverse genetic approaches have relied on the
      availability of a carefully selected set of transposon insertions spread
      throughout the genome to allow the manipulation of the region in the vicinity of
      each insertion. Lastly, the ability to transform Drosophila with single copy
      transgenes using transposons or site-specific integration using the PhiC31
      integrase has allowed numerous manipulations, including the ability to create and
      integrate genomic rescue constructs, generate duplications, RNAi knock-out
      technology, binary expression systems like the GAL4/UAS system as well as other
      methods. Here, we will discuss the most useful methodologies to interrogate the
      fruit fly genome in vivo focusing on chemical mutagenesis, transposons and
      transgenes. Genome engineering approaches based on nucleases and RNAi technology
      are discussed in following chapters. 

PMID- 24583114
TI  - Gene targeting in rats using transcription activator-like effector nucleases.
AB  - The rat is a model of choice to understanding gene function and modeling human
      diseases. Since recent years, successful engineering technologies using gene
      specific nucleases have been developed to gene edit the genome of different
      species, including the rat. This development has become important for the
      creation of new rat animals models of human diseases, analyze the role of genes
      and express recombinant proteins. Transcription activator-like (TALE) nucleases
      are designed nucleases consist of a DNA binding domain fused to a nuclease domain
      capable of cleaving the targeted DNA. We describe a detailed protocol for
      generating knockout rats via microinjection of TALE nucleases into fertilized
      eggs. This technology is an efficient, cost- and time-effective method for
      creating new rat models. 

PMID- 24583115
TI  - Integrative analysis of many RNA-seq datasets to study alternative splicing.
AB  - Alternative splicing is an important gene regulatory mechanism that dramatically
      increases the complexity of the proteome. However, how alternative splicing is
      regulated and how transcription and splicing are coordinated are still poorly
      understood, and functions of transcript isoforms have been studied only in a few
      limited cases. Nowadays, RNA-seq technology provides an exceptional opportunity
      to study alternative splicing on genome-wide scales and in an unbiased manner.
      With the rapid accumulation of data in public repositories, new challenges arise
      from the urgent need to effectively integrate many different RNA-seq datasets for
      study alterative splicing. This paper discusses a set of advanced computational
      methods that can integrate and analyze many RNA-seq datasets to systematically
      identify splicing modules, unravel the coupling of transcription and splicing,
      and predict the functions of splicing isoforms on a genome-wide scale. 

PMID- 24583116
TI  - Sequence-specific recognition of DNA nanostructures.
AB  - DNA is the most exploited biopolymer for the programmed self-assembly of objects
      and devices that exhibit nanoscale-sized features. One of the most useful
      properties of DNA nanostructures is their ability to be functionalized with
      additional non-nucleic acid components. The introduction of such a component is
      often achieved by attaching it to an oligonucleotide that is part of the
      nanostructure, or hybridizing it to single-stranded overhangs that extend beyond
      or above the nanostructure surface. However, restrictions in nanostructure design
      and/or the self-assembly process can limit the suitability of these procedures.
      An alternative strategy is to couple the component to a DNA recognition agent
      that is capable of binding to duplex sequences within the nanostructure. This
      offers the advantage that it requires little, if any, alteration to the
      nanostructure and can be achieved after structure assembly. In addition, since
      the molecular recognition of DNA can be controlled by varying pH and ionic
      conditions, such systems offer tunable properties that are distinct from simple
      Watson-Crick hybridization. Here, we describe methodology that has been used to
      exploit and characterize the sequence-specific recognition of DNA nanostructures,
      with the aim of generating functional assemblies for bionanotechnology and
      synthetic biology applications. 

PMID- 24583117
TI  - Gold nanoparticles explore cells: cellular uptake and their use as intracellular
      probes.
AB  - Understanding uptake of nanomaterials by cells and their use for intracellular
      sensing is important for studying their interaction and toxicology as well as for
      obtaining new biological insight. Here, we investigate cellular uptake and
      intracellular dynamics of gold nanoparticles and demonstrate their use in
      reporting chemical information from the endocytotic pathway and cytoplasm. The
      intracellular gold nanoparticles serve as probes for surface-enhanced Raman
      spectroscopy (SERS) allowing for biochemical characterisation of their local
      environment. In particular, in this work we compare intracellular SERS using non
      functionalised and functionalised nanoparticles in their ability to segregate
      different but closely related cell phenotypes. The results indicate that
      functionalised gold nanoparticles are more efficient in distinguishing between
      different types of cells. Our studies pave the way for understanding the uptake
      of gold nanoparticles and their utilisation for SERS to give rise to a greater
      biochemical understanding in cell-based therapies. 

PMID- 24583118
TI  - Using yeast to model calcium-related diseases: example of the Hailey-Hailey
      disease.
AB  - Cross-complementation studies offer the possibility to overcome limitations
      imposed by the inherent complexity of multicellular organisms in the study of
      human diseases, by taking advantage of simpler model organisms like the budding
      yeast Saccharomyces cerevisiae. This review deals with, (1) the use of S.
      cerevisiae as a model organism to study human diseases, (2) yeast-based screening
      systems for the detection of disease modifiers, (3) Hailey-Hailey as an example
      of a calcium-related disease, and (4) the presentation of a yeast-based model to
      search for chemical modifiers of Hailey-Hailey disease. The preliminary
      experimental data presented and discussed here show that it is possible to use
      yeast as a model system for Hailey-Hailey disease and suggest that in all
      likelihood, yeast has the potential to reveal candidate drugs for the treatment
      of this disorder. This article is part of a Special Issue entitled: Calcium
      signaling in health and disease. Guest Editors: Geert Bultynck, Jacques Haiech,
      Claus W. Heizmann, Joachim Krebs, and Marc Moreau. 

PMID- 24583120
TI  - Protein transport by the bacterial Tat pathway.
AB  - The twin-arginine translocation (Tat) system accomplishes the remarkable feat of
      translocating large - even dimeric - proteins across tightly sealed energy
      transducing membranes. All of the available evidence indicates that it is unique
      in terms of both structure and mechanism; however its very nature has hindered
      efforts to probe the core translocation events. At the heart of the problem is
      the fact that two large sub-complexes are believed to coalesce to form the active
      translocon, and 'capturing' this translocation event has been too difficult.
      Nevertheless, studies on the individual components have come a long way in recent
      years, and structural studies have reached the point where educated guesses can
      be made concerning the most interesting aspects of Tat. In this article we review
      these studies and the emerging ideas in this field. This article is part of a
      Special Issue entitled: Protein trafficking and secretion in bacteria. Guest
      Editors: Anastassios Economou and Ross Dalbey. 

PMID- 24583119
TI  - MTOR-independent induction of autophagy in trabecular meshwork cells subjected to
      biaxial stretch.
AB  - The trabecular meshwork (TM) is part of a complex tissue that controls the exit
      of aqueous humor from the anterior chamber of the eye, and therefore helps
      maintaining intraocular pressure (IOP). Because of variations in IOP with
      changing pressure gradients and fluid movement, the TM and its contained cells
      undergo morphological deformations, resulting in distention and stretching. It is
      therefore essential for TM cells to continuously detect and respond to these
      mechanical forces and adapt their physiology to maintain proper cellular function
      and protect against mechanical injury. Here we demonstrate the activation of
      autophagy, a pro-survival pathway responsible for the degradation of long-lived
      proteins and organelles, in TM cells when subjected to biaxial static stretch
      (20% elongation), as well as in high-pressure perfused eyes (30mmHg).
      Morphological and biochemical markers for autophagy found in the stretched cells
      include elevated LC3-II levels, increased autophagic flux, and the presence of
      autophagic figures in electron micrographs. Furthermore, our results indicate
      that the stretch-induced autophagy in TM cells occurs in an MTOR- and BAG3
      independent manner. We hypothesize that activation of autophagy is part of the
      physiological response that allows TM cells to cope and adapt to mechanical
      forces. 

PMID- 24583121
TI  - SecA-mediated targeting and translocation of secretory proteins.
AB  - More than 30 years of research have revealed that the dynamic nanomotor SecA is a
      central player in bacterial protein secretion. SecA associates with the SecYEG
      channel and transports polypeptides post-translationally to the trans side of the
      cytoplasmic membrane. It comprises a helicase-like ATPase core coupled to two
      domains that provide specificity for preprotein translocation. Apart from SecYEG,
      SecA associates with multiple ligands like ribosomes, nucleotides, lipids,
      chaperones and preproteins. It exerts its essential contribution in two phases.
      First, SecA, alone or in concert with chaperones, helps mediate the targeting of
      the secretory proteins from the ribosome to the membrane. Next, at the membrane
      it converts chemical energy to mechanical work and translocates preproteins
      through the SecYEG channel. SecA is a highly dynamic enzyme, it exploits disorder
      order kinetics, swiveling and dissociation of domains and dimer to monomer
      transformations that are tightly coupled with its catalytic function. Preprotein
      signal sequences and mature domains exploit these dynamics to manipulate the
      nanomotor and thus achieve their export at the expense of metabolic energy. This
      article is part of a Special Issue entitled: Protein trafficking and secretion in
      bacteria. Guest Editors: Anastassios Economou and Ross Dalbey.

PMID- 24583122
TI  - Microcompartmentalized cell-free protein synthesis in semipermeable microcapsules
      composed of polyethylenimine-coated alginate.
AB  - We describe microcompartmentalized cell-free protein synthesis in semipermeable
      microcapsules prepared from water-in-oil-in-water droplets by a rupture-induced
      encapsulation method. An aqueous solution of template DNA coding for green
      fluorescent protein and enzymes for the cell-free protein synthesis was aliquoted
      into water-in-oil droplets using a microfluidic device, and the droplets were
      transformed into semipermeable microcapsules. Substrates for protein synthesis
      diffused into the microcapsules through their semipermeable polyion complex
      membranes composed of polyethylenimine-coated alginate. Cell-free protein
      synthesis was confirmed by detection of the fluorescence of the synthesized green
      fluorescence protein in the microcapsules. We also used this
      microcompartmentalized system to synthesize protein from a single molecule of
      template DNA encapsulated by limiting dilution. 

PMID- 24583123
TI  - Successful treatment of advanced Ebola virus infection with T-705 (favipiravir)
      in a small animal model.
AB  - Outbreaks of Ebola hemorrhagic fever in sub-Saharan Africa are associated with
      case fatality rates of up to 90%. Currently, neither a vaccine nor an effective
      antiviral treatment is available for use in humans. Here, we evaluated the
      efficacy of the pyrazinecarboxamide derivative T-705 (favipiravir) against Zaire
      Ebola virus (EBOV) in vitro and in vivo. T-705 suppressed replication of Zaire
      EBOV in cell culture by 4log units with an IC90 of 110MUM. Mice lacking the type
      I interferon receptor (IFNAR(-)(/)(-)) were used as in vivo model for Zaire EBOV
      induced disease. Initiation of T-705 administration at day 6 post infection
      induced rapid virus clearance, reduced biochemical parameters of disease
      severity, and prevented a lethal outcome in 100% of the animals. The findings
      suggest that T-705 is a candidate for treatment of Ebola hemorrhagic fever. 

PMID- 24583124
TI  - SALMFamide salmagundi: the biology of a neuropeptide family in echinoderms.
AB  - The SALMFamides are a family of neuropeptides that occur in species belonging to
      the phylum Echinodermata. The prototypes for this neuropeptide family (S1 and S2)
      were discovered in starfish but subsequently SALMFamides were identified in other
      echinoderms. There are two types of SALMFamides: L-type, which have the C
      terminal motif SxLxFamide, and F-type, which have the C-terminal motif
      SxFxFamide. They are derived from two types of precursor proteins: an L-type
      SALMFamide precursor, which comprises only L-type or L-type-like SALMFamides and
      an F-type SALMFamide precursor, which contains several F-type or F-type-like
      SALMFamides and, typically, one or more L-type SALMFamides. Thus, SALMFamides
      occur as heterogeneous mixtures of neuropeptides - a SALMFamide salmagundi.
      SALMFamides are produced by distinct populations of neurons in echinoderm larval
      and adult nervous systems and are present in the innervation of neuromuscular
      organs. Both L-type and F-type SALMFamides cause muscle relaxation in echinoderms
      and, for example, in starfish this effect of SALMFamides may mediate neural
      control of cardiac stomach eversion in species that feed extra-orally (e.g.,
      Asterias rubens). The SALMFamide S1 also causes inhibition of neural release of a
      relaxin-like gonadotropin in the starfish Asterina pectinifera. An important
      issue that remains to be resolved are the relationships of SALMFamides with
      neuropeptides that have been identified in other phyla. However, it has been
      noted that the C-terminal SxLxFamide motif of L-type SALMFamides is a feature of
      some members of a bilaterian neuropeptide family that includes gonadotropin
      inhibitory hormone (GnIH) in vertebrates and SIFamide-type neuropeptides in
      protostomes. Similarly, the C-terminal FxFamide motif of F-type SALMFamides is a
      feature of vertebrate QRFP (26RFa)-type neuropeptides. These sequence
      similarities may provide a basis for molecular identification of receptors that
      mediate effects of SALMFamides. Furthermore, analysis of the actions of the
      heterogeneous mixtures of SALMFamides that occur in echinoderms may provide new
      insights into the physiological significance of the general phenomenon of
      precursor proteins that give rise to neuropeptide "cocktails".

PMID- 24583125
TI  - Kindlin-2 inhibits serous epithelial ovarian cancer peritoneal dissemination and
      predicts patient outcomes.
AB  - Kindlin-2 has been known to promote most cancer progression through regulation of
      multiple signaling pathways. However, a novel tumor suppressive role of Kindlin-2
      was identified in serous epithelial ovarian cancer progression, which sharply
      contrasts to the tumor promoting roles for Kindlin-2 in most other cancers. While
      we demonstrated that Kindlin-2 was highly expressed in control tissues, a drastic
      low expression of Kindlin-2 was found in the tumor tissues of serous epithelial
      ovarian cancer, especially in the high-grade serous epithelial ovarian cancer.
      Importantly, Kindlin-2 inhibited serous epithelial ovarian cancer cell peritoneal
      dissemination in a mouse model. For clinical relevance, low Kindlin-2 expression
      correlated with higher tumor grade and older patients. Intriguingly, decreased
      Kindlin-2 expression predicts poor overall and progression-free survivals in
      serous epithelial ovarian cancer patients. Mechanistically, Kindlin-2 induced a
      mesenchymal to epithelial transition in serous epithelial ovarian cancer cells,
      at least in part, by up-regulation of estrogen receptor alpha which was recruited
      to the promoter of E-cadherin and thereby enhanced the transcription of E
      cadherin. Collectively, we concluded that inadequate Kindlin-2 is an independent
      risk factor for serous epithelial ovarian cancer patients. 

PMID- 24583126
TI  - Defective adipose tissue development associated with hepatomegaly in cathepsin E
      deficient mice fed a high-fat diet.
AB  - Cathepsin E is an intracellular aspartic proteinase, which is predominantly
      distributed in immune-related and epithelial cells. However, the role of the
      enzyme in adipose tissues remains unknown. In this study, we investigated the
      characteristics of cathepsin E-deficient (CatE(-/-)) mice fed a high-fat diet
      (HFD), as a mouse model of obesity. HFD-fed CatE(-/-) mice displayed reduced body
      weight gain and defective development of white adipose tissue (WAT) and brown
      adipose tissue (BAT), compared with HFD-fed wild-type mice. Moreover, fat-induced
      CatE(-/-) mice showed abnormal lipid accumulation in non-adipose tissues
      characterized by hepatomegaly, which is probably due to defective adipose tissue
      development. Detailed pathological and biochemical analyses showed that
      hepatomegaly was accompanied by hepatic steatosis and hypercholesterolemia in HFD
      induced CatE(-/-) mice. In fat-induced CatE(-/-) mice, the number of macrophages
      infiltrating into WAT was significantly lower than in fat-induced wild-type mice.
      Thus, the impaired adipose tissue development in HFD-induced CatE(-/-) mice was
      probably due to reduced infiltration of macrophages and may lead to hepatomegaly
      accompanied by hepatic steatosis and hypercholesterolemia. 

PMID- 24583127
TI  - Synthesis and evaluation of a radioiodinated peptide probe targeting alphavbeta6
      integrin for the detection of pancreatic ductal adenocarcinoma.
AB  - INTRODUCTION: Pancreatic ductal adenocarcinoma (PDAC) remains a major cause of
      cancer-related death. Since significant upregulation of alphavbeta6 integrin has
      been reported in PDAC, this integrin is a promising target for PDAC detection. In
      this study, we aimed to develop a radioiodinated probe for the imaging of
      alphavbeta6 integrin-positive PDAC with single-photon emission computed
      tomography (SPECT). METHODS: Four peptide probes were synthesized and screened by
      competitive and saturation binding assays using 2 PDAC cell lines (AsPC-1,
      alphavbeta6 integrin-positive; MIA PaCa-2, alphavbeta6 integrin-negative). The
      probe showing the best affinity was used to study the biodistribution assay, an
      in vivo blocking study, and SPECT imaging using tumor bearing mice.
      Autoradiography and immunohistochemical analysis were also performed. RESULTS:
      Among the 4 probes examined in this study, (125)I-IFMDV2 showed the highest
      affinity for alphavbeta6 integrin expressed in AsPC-1 cells and no affinity for
      MIA PaCa-2 cells. The accumulation of (125)I-IFMDV2 in the AsPC-1 xenograft was 3
      5 times greater than that in the MIA PaCa-2 xenograft, consistent with the
      expression of alphavbeta6 integrin in each xenograft, and confirmed by
      immunohistochemistry. Pretreatment with excess amounts of A20FMDV2 significantly
      blocked the accumulation of (125)I-IFMDV2 in the AsPC-1 xenograft, but not in the
      MIA PaCa-2 xenograft. Furthermore, (123)I-IFMDV2 enabled clear visualization of
      the AsPC-1 xenograft. CONCLUSION: (123)I-IFMDV2 is a potential SPECT probe for
      the imaging of alphavbeta6 integrin in PDAC.

PMID- 24583128
TI  - CXCL5 knockdown expression inhibits human bladder cancer T24 cells proliferation
      and migration.
AB  - CXCL5 (epithelial neutrophil activating peptide-78) which acts as a potent
      chemoattractant and activator of neutrophil function was reported to play a
      multifaceted role in tumorigenesis. To investigate the role of CXCL5 in bladder
      cancer progression, we examined the CXCL5 expression in bladder cancer tissues by
      real-time PCR and Western blot, additionally, we used shRNA-mediated silencing to
      generate stable CXCL5 silenced bladder cancer T24 cells and defined its
      biological functions. Our results demonstrated that mRNA and protein of CXCL5 is
      increased in human bladder tumor tissues and cell lines, down-regulation of CXCL5
      in T24 cells resulted in significantly decreased cell proliferation, migration
      and increased cell apoptosis in vitro through Snail, PI3K-AKT and ERK1/2
      signaling pathways. These data suggest that CXCL5 is critical for bladder tumor
      growth and progression, it may represent a potential application in cancer
      diagnosis and therapy. 

PMID- 24583129
TI  - JAZF1 can regulate the expression of lipid metabolic genes and inhibit lipid
      accumulation in adipocytes.
AB  - JAZF1 is a newly identified gene with unknown functions. A recent genome-wide
      association study showed that JAZF1 is associated with type 2 diabetes and is
      highly expressed in liver and adipose tissue. Studies have demonstrated that
      JAZF1 is the co-repressor for nuclear orphan receptor TAK1, whereas most nuclear
      orphan receptor family members are involved in the regulation of lipid
      metabolism. Therefore, JAZF1 could be closely related to glycolipid metabolism.
      In this study, JAZF1 was significantly upregulated during the induced
      differentiation process of 3T3-L1 preadipocytes. The overexpression of JAZF1
      inhibited lipid accumulation in differentiated mature 3T3-L1 adipocytes and
      significantly inhibited the expression of SREBPl, ACC, and FAS, which were
      important in lipid synthesis, while upregulating the expression of key enzyme
      hormone-sensitive lipase in lipoclasis. Moreover, SREBPl exhibited an inhibitory
      function on the expression of JAZF1. SREBP1 reversed the inhibitory action on
      lipid accumulation of JAZF1. SREBP1 and JAZF1 were observed to regulate each
      other in adipocytes. Therefore, JAZF1 could regulate the expression of particular
      genes related to lipid metabolism and inhibit lipid accumulation in adipocytes.
      This result suggests that JAZF1 may be a potential target for the treatment of
      diseases, such as obesity and lipid metabolism disorders. 

PMID- 24583130
TI  - Elicitation of metastasis associated protein 2 expression in the phagocytosis by
      murine testicular Sertoli cells.
AB  - Efficient phagocytic clearance of apoptotic spermatogenic cells and residual
      bodies (RBs) by Sertoli cells (SCs) is crucial for functional mature
      spermatogenesis. However, little is known about the molecular mechanisms
      underlying this SCs function. Herein, we reported for the first time that SCs
      expressing metastasis associated protein 2 (Mta2), a chromatin modifier playing a
      critical role in modifying DNA accessibility for transcriptional regulation, was
      steadily up-regulated when SCs were co-cultured with RBs. The most efficient
      stimulatory substrates for the inducement of phagocytosis-elicited Mta2
      expression were RBs and fragments from apoptotic spermatocytes. Furthermore, one
      major result of this response is the transcriptional repression of follicle
      stimulating hormone receptor gene (Fshr) expression during phagocytosis, which
      should lead to a low level of circulated FSH because effects of FSH on
      spermatogenesis is fundamentally regulated by the down-regulation of Fshr after
      exposure to FSH. Given that high concentration of circulated FSH inhibits SCs
      phagocytic activity and impairment of MTA2 expression is associated with the
      abnormal high level of serum FSH, our present results suggest that the
      FSH/MTA2/Fshr cascade may serve as an indispensable negative feedback mechanism
      to help to maintain low level of circulated FSH, which is required for the normal
      occurrence of SCs phagocytosis. 

PMID- 24583132
TI  - The Y-located gonadoblastoma gene TSPY amplifies its own expression through a
      positive feedback loop in prostate cancer cells.
AB  - The testis-specific protein Y-encoded (TSPY) is a repetitive gene located on the
      gonadoblastoma region of the Y chromosome, and has been considered to be the
      putative gene for this oncogenic locus on the male-only chromosome. It is
      expressed in spermatogonial cells and spermatocytes in normal human testis, but
      abundantly in gonadoblastoma, testicular germ cell tumors and a variety of
      somatic cancers, including melanoma, hepatocellular carcinoma and prostate
      cancer. Various studies suggest that TSPY accelerates cell proliferation and
      growth, and promotes tumorigenesis. In this report, we show that TSPY could bind
      directly to the chromatin/DNA at exon 1 of its own gene, and greatly enhance the
      transcriptional activities of the endogenous gene in the LNCaP prostate cancer
      cells. Domain mapping analyses of TSPY have localized the critical and sufficient
      domain to the SET/NAP-domain. These results suggest that TSPY could efficiently
      amplify its expression and oncogenic functions through a positive feedback loop,
      and contribute to the overall tumorigenic processes when it is expressed in
      various human cancers. 

PMID- 24583131
TI  - Construction and direct electrochemistry of orientation controlled laccase
      electrode.
AB  - A laccase has multiple redox centres. Chemisorption of laccases on a gold
      electrode through a polypeptide tag introduced at the protein surface provides an
      isotropic orientation of laccases on the Au surface, which allows the orientation
      dependent study of the direct electrochemistry of laccase. In this paper, using
      genetic engineering technology, two forms of recombinant laccase which has Cys
      6*His tag at the N or C terminus were generated. Via the Au-S linkage, the
      recombinant laccase was assembled orientationally on gold electrode. A direct
      electron transfer and a bioelectrocatalytic activity toward oxygen reduction were
      observed on the two orientation controlled laccase electrodes, but their
      electrochemical behaviors were found to be quite different. The orientation of
      laccase on the gold electrode affects both the electron transfer pathway and the
      electron transfer efficiency of O2 reduction. The present study is helpful not
      only to the in-depth understanding of the direct electrochemistry of laccase, but
      also to the development of laccase-based biofuel cells. 

PMID- 24583133
TI  - Deregulated unfolded protein response in chronic wounds of diabetic ob/ob mice: a
      potential connection to inflammatory and angiogenic disorders in diabetes
      impaired wound healing.
AB  - Type-2 diabetes mellitus (T2D) represents an important metabolic disorder, firmly
      connected to obesity and low level of chronic inflammation caused by deregulation
      of fat metabolism. The convergence of chronic inflammatory signals and nutrient
      overloading at the endoplasmic reticulum (ER) leads to activation of ER-specific
      stress responses, the unfolded protein response (UPR). As obesity and T2D are
      often associated with impaired wound healing, we investigated the role of UPR in
      the pathologic of diabetic-impaired cutaneuos wound healing. We determined the
      expression patterns of the three UPR branches during normal and diabetes-impaired
      skin repair. In healthy and diabetic mice, injury led to a strong induction of
      BiP (BiP/Grp78), C/EBP homologous protein (CHOP) and splicing of X-box-binding
      protein (XBP)1. Diabetic-impaired wounds showed gross and sustained induction of
      UPR associated with increased expression of the pro-inflammatory chemokine
      macrophage inflammatory protein (MIP)2 as compared to normal healing wounds. In
      vitro, treatment of RAW264.7 macrophages with tunicamycin, and subsequently
      stimulation with lipopolysaccharide (LPS) and interferon (IFN)-gamma enhances
      MIP2 mRNA und protein expression compared to proinflammatory stimulation alone.
      However, LPS/IFNgamma induced vascular endothelial growth factor (VEGF)
      production was blunted by tunicamycin induced-ER stress. Hence, UPR is activated
      following skin injury, and functionally connected to the production of
      proinflammatory mediators. In addition, prolongation of UPR in diabetic non
      healing wounds aggravates ER stress and weakens the angiogenic phenotype of wound
      macrophages. 

PMID- 24583135
TI  - Detection of IgE binding component to infliximab in a patient with infliximab
      induced anaphylaxis.

PMID- 24583134
TI  - Interleukin-13-induced MUC5AC expression is regulated by a PI3K-NFAT3 pathway in
      mouse tracheal epithelial cells.
AB  - Interleukin-13 (IL-13) plays a critical role in asthma mucus overproduction,
      while the mechanisms underlying this process are not fully elucidated. Previous
      studies showed that nuclear factor of activated T cells (NFAT) is involved in the
      pathogenesis of asthma, but whether it can directly regulate IL-13-induced mucus
      (particularly MUC5AC) production is still not clear. Here we showed that IL-13
      specifically induced NFAT3 activation through promoting its dephosphorylation in
      air-liquid interface (ALI) cultures of mouse tracheal epithelial cells (mTECs).
      Furthermore, both Cyclosporin A (CsA, a specific NFAT inhibitor) and LY294002 (a
      Phosphoinositide 3-kinase (PI3K) inhibitor) significantly blocked IL-13-induced
      MUC5AC mRNA and protein production through the inhibition of NFAT3 activity. We
      also confirmed that CsA could not influence the forkhead Box A2 (Foxa2) and mouse
      calcium dependent chloride channel 3 (mClca3) expression in IL-13-induced MUC5AC
      production, which both are known to be important in IL-13-stimulated mucus
      expression. Our study is the first to demonstrate that the PI3K-NFAT3 pathway is
      positively involved in IL-13-induced mucus production, and provided novel
      insights into the molecular mechanism of asthma mucus hypersecretion. 

PMID- 24583136
TI  - Diagnostic utility of concentrated Mus m 1 allergen extract in humans.

PMID- 24583137
TI  - Potential predictors of relapse after treatment of asthma exacerbations in
      children.
AB  - BACKGROUND: Knowledge of factors that affect relapse will allow close monitoring
      of patients at risk, resulting in a decreased rate of readmission to the
      emergency department. OBJECTIVE: To determine risk factors associated with
      relapse within 7 days after treatment of asthma exacerbations in children.
      METHODS: This was a multicenter, prospective study of children with asthma
      attacks. Patients between the ages of 6 months and 17 years who met the criteria
      between June 2009 and September 2012 were considered. RESULTS: The study included
      1177 patients (775 males [65.8%]) with a mean (SD) age of 70.72 (48.24) months.
      Of them, 199 (16.9%) had a relapse within 1 week after being discharged from the
      hospital. Factors independently associated with relapse identified by a logistic
      regression model for the 1,177 study visits were having taken a short-acting
      inhaled beta2-agonist within 6 hours before admission (odds ratio [OR], 2.43; 95%
      confidence interval [CI], 1.728-3.426; P = .001), presence of retraction on
      physical examination (OR, 1.76; 95% CI, 1.123-2.774; P = .01), no prescription
      for high-dose inhaled steroids on release (OR, 2.02; 95% CI, 1.370-3.002; P <
      .001), and not being given a written instructional plan (OR, 1.55; 95% CI, 1.080
      2.226; P = .02). CONCLUSION: Whereas having taken short-acting beta2-agonists
      within 6 hours before admission and the presence of retractions on physical
      examination increased the risk of relapse after treatment of the acute attack,
      being given high-dose inhaled steroids and a written instructional plan when
      being sent home reduced the risk.

PMID- 24583138
TI  - The clinical application of three-dimensional motion capture (4D): a novel
      approach to quantify the dynamics of facial animations.
AB  - The aim of this pilot study was to evaluate the feasibility of measuring the
      change in magnitude, speed, and motion similarity of facial animations in head
      and neck oncology patients, before and after lip split mandibulotomy. Seven
      subjects (four males, three females) aged 42-80 years were recruited. The
      subjects were asked to perform four facial animations (maximal smile, lip purse,
      cheek puff, and grimace) from rest to maximal position. The animations were
      captured using a Di4D motion capture system, which recorded 60 frames/s. Nine
      facial soft tissue landmarks were manually digitized on the first frame of the
      three-dimensional image of each animation by the same operator and were tracked
      automatically for the sequential frames. The intra-operator digitization error
      was within 0.4mm. Lip purse and maximal smile animations showed the least amount
      of change in magnitude (0.2mm) following surgery; speed difference was least for
      smile animation (-0.1mm/s). Motion similarity was found to be highest for lip
      purse animation (0.78). This pilot study confirmed that surgery did influence the
      dynamics of facial animations, and the Di4D capture system can be regarded as a
      feasible objective tool for assessing the impact of surgical interventions on
      facial soft tissue movements. 

PMID- 24583139
TI  - Clinicopathological prognostic factors of oral tongue squamous cell carcinoma: a
      retrospective study of 202 cases.
AB  - Although several histopathological parameters and grading systems have been
      described as predictive of the treatment response and outcome of oral squamous
      cell carcinoma (OSCC), none is universally accepted. A new scoring system, the
      histological risk model, was recently described to be a powerful predictive tool
      for recurrence and overall survival in OSCC. The aim of this study was to verify
      the predictive role of the histological risk model in a cohort of 202 patients at
      all stages of oral/mobile tongue squamous cell carcinoma (OTSCC). Demographic and
      clinical data were collected from the medical records and the tumours were
      evaluated using the histological risk model. Statistical analyses were performed
      using the chi(2) test, the Kaplan-Meier method, and the Cox regression model. The
      histological risk model showed no statistical correlation with demographic or
      clinical parameters and did not Predict the outcome of the OTSCC patients.
      However, multivariate regression analysis revealed a significant correlation of
      the clinical disease stage with the disease outcome. Despite major efforts to
      identify new predictive parameters and histological systems, clinical features
      are still the most reliable prognostic factors for patients with OTSCC. 

PMID- 24583140
TI  - The impact of a modified cutting flute implant design on osseointegration.
AB  - Information concerning the effects of the implant cutting flute design on initial
      stability and its influence on osseointegration in vivo is limited. This study
      evaluated the early effects of implants with a specific cutting flute design
      placed in the sheep mandible. Forty-eight dental implants with two different
      macro-geometries (24 with a specific cutting flute design - Blossom group; 24
      with a self-tapping design - DT group) were inserted into the mandibular bodies
      of six sheep; the maximum insertion torque was recorded. Samples were retrieved
      and processed for histomorphometric analysis after 3 and 6 weeks. The mean
      insertion torque was lower for Blossom implants (P<0.001). No differences in
      histomorphometric results were observed between the groups. At 3 weeks, P=0.58
      for bone-to-implant contact (BIC) and P=0.52 for bone area fraction occupied
      (BAFO); at 6 weeks, P=0.55 for BIC and P=0.45 for BAFO. While no
      histomorphometric differences were observed, ground sections showed different
      healing patterns between the implants, with better peri-implant bone organization
      around those with the specific cutting flute design (Blossom group). Implants
      with the modified cutting flute design had a significantly reduced insertion
      torque compared to the DT implants with a traditional cutting thread, and
      resulted in a different healing pattern. 

PMID- 24583141
TI  - Development of a participatory tool for the evaluation of Village Animal Health
      Workers in Cambodia.
AB  - In countries with a lack of primary care systems, health workers are of crucial
      importance to improving the delivery of health and animal health services at
      community level. But somehow they are rarely evaluated and usually with a top
      down approach. This is the case in Cambodia, where thousands of Village Animal
      Health Workers (VAHWs) have been trained by the government, and where no
      standardized evaluation tool is available to accurately assess the situation.
      Based on methodology developed by the French NGO Agronomes et Veterinaires Sans
      Frontieres (AVSF) in Madagascar for farmers' association evaluation, we developed
      our own participatory methods to collect information about the VAHW context and
      build a criteria grid for their evaluation. In this framework, several
      participatory approaches were used such as problem trees, semi-structured
      interviews, pair-wise ranking and focus groups. The grid was built with the help
      of relevant stakeholders involved in the animal health system in Cambodia in
      order to (i) identify VAHW functions; (ii) set up criteria and associated
      questionnaires, and (iii) score the grid with all the stakeholders. The tool was
      divided into five categories of evaluation criteria: sustainability, treatment,
      production, vaccination and disease reporting. Our approach looked at local
      indicators of success developed and used by VAHWs themselves, which should lead
      to better acceptability of evaluation. This method gave priority to dialog aiming
      to engage decision makers and other stakeholders in a mutual learning process and
      could be applied in other countries to develop trust between health workers and
      official service representatives as well as to foster corrective action after
      evaluation. 

PMID- 24583142
TI  - SV40 TAg mouse models of cancer.
AB  - The discovery of a number of viruses with the ability to induce tumours in
      animals and transform human cells has vastly impacted cancer research. Much of
      what is known about tumorigenesis today regarding tumour drivers and tumour
      suppressors has been discovered through experiments using viruses. The SV40 virus
      has proven extremely successful in generating transgenic models of many human
      cancer types and this review provides an overview of these models and seeks to
      give evidence as to their relevance in this modern era of personalised medicine
      and technological advancements. 

PMID- 24583143
TI  - Modulation of phenotypic and functional maturation of murine bone-marrow-derived
      dendritic cells (BMDCs) induced by cadmium chloride.
AB  - Cadmium (Cd(2+)) has been classified as a type I human carcinogen by the
      International Agency for Research on Cancer. In the present study, we are going
      to report for the first time on the detailed modulation of phenotypic and
      functional maturation of murine bone marrow-derived dendritic cells (BMDCs)
      induced by cadmium chloride. Dendritic cells (DCs) are major modulators in the
      whole immune system. One dynamic field of research is the manipulation of DCs as
      pharmacological targets to screen novel biological modifiers for the treatment of
      tumor, inflammatory and autoimmune disorders. Phenotypic and functional
      maturation of BMDCs was evaluated by phase-contrast light microscope for primary
      cultures, flow cytometry (FCM) for important DC markers, reverse-transcriptase
      PCR and enzyme linked immunosorbent assay (ELISA) for cytokines. Cd(2+)-induced
      BMDC death was also performed by comet assay. Our results elucidated that Cd(2+)
      suppressed maturation of BMDCs via changes as reflected by the decreased
      expression of key surface molecules such as MHCII and CD40, and also by releasing
      the lower level of IL-12p70. The change of expression of other co-stimulatory
      molecules such as CD86 and CD80 was not so significant. However, it was found
      that cadmium promotes releasing a higher level of IL-23 from BMDCs. So from our
      study, it can be concluded that cadmium may be one of the potent
      immunosuppressive agents through the blockage of DC maturation and function. 

PMID- 24583144
TI  - Effects and mechanisms of Geniposide on rats with adjuvant arthritis.
AB  - Geniposide (GE), an iridoid glycoside compound, is the major active ingredient of
      Gardenia jasminoides Ellis (GJ) fruit which has anti-inflammatory and other
      important therapeutic activities. The aim of this study was to investigate the
      effects of GE on adjuvant arthritis (AA) rats and its possible mechanisms. AA was
      induced by injecting with Freund's complete adjuvant (FCA). Male SD rats were
      subjected to treatment with GE at 30, 60 and 120mg/kg from days 18 to 24 after
      immunization. Lymphocyte proliferation was assessed by MTT. Interleukin (IL)-6,
      IL-17, IL-4 and transforming growth factor-beta 1 (TGF-beta1) were determined by
      ELISA. c-Jun N-terminal kinase (JNK) and phospho-JNK (p-JNK) were detected by
      Western blot. GE (60, 120mg/kg) significantly relieved the secondary hind paw
      swelling and arthritis index, along with decreased Th17-cells cytokines and
      increased Treg-cell cytokines in mesenteric lymph node lymphocytes (MLNL) and
      peripheral blood lymphocytes (PBL) of AA rats. In addition, GE decreased the
      expression of p-JNK in MLNL and PBL of AA rats. In vivo study, it was also
      observed that GE attenuated histopathologic changes of MLN in AA rats.
      Collectively, GE might exert its anti-inflammatory and immunoregulatory effects
      through inducing Th17 cell immune tolerance and enhancing Treg cell-mediated
      activities by down-regulating the expression of p-JNK. The mechanisms of GE on
      JNK signaling in MLNL and PBL may play critical roles in the pathogenesis of
      rheumatoid arthritis. 

PMID- 24583145
TI  - The chemokine-like factor 1 induces asthmatic pathological change by activating
      nuclear factor-kappaB signaling pathway.
AB  - CKLF1, which exhibits chemotactic activities on a wide spectrum of leukocytes, is
      up-regulated during the progress of asthma. It plays a vital role in the
      pathogenesis of pulmonary disease. Here, we report that CKLF1 has the capability
      to activate the NF-kappaB signaling pathway leading to the pathological change in
      the lung. The HEK293-CCR4 cell line, which expressed CCR4 stably, was established
      and screened. Western blot analysis was performed to determine the expression of
      NF-kappaB in HEK293-CCR4 and A549 cells following the C27 (10MUg/ml) added in
      each well at different times. These results showed that C27 (10MUg/ml) time
      dependently induced the accumulation of NF-kappaB in the nucleus of HEK293-CCR4
      and A549 cells. In addition, CKLF1 plasmid (100MUg) injection and electroporation
      led to the asthmatic change in the lung in mice as shown by HE and PAS staining.
      Furthermore, it was confirmed that CKLF1 significantly up-regulated the p-IkappaB
      expression, decreased the IkappaB expression, and suppressed the NF-kappaB
      expression in the cytoplasm of pulmonary tissue in vivo study. Intriguingly, an
      enhanced nuclear accumulation of NF-kappaB was observed in the lung of pCDI-CKLF1
      electroporated mice, compared to that in the sham group. Therefore, the NF-kappaB
      signaling pathway was involved in the asthmatic change induced by CKLF1, among
      which CCR4 might play a crucial role. 

PMID- 24583146
TI  - CCL2 mediates anti-fibrotic effects in human fibroblasts independently of CCR2.
AB  - CCL2 is known for its major role as a chemoattractant of monocytes for
      immunological surveillance and to site of inflammation. CCL2 acts mainly through
      the G-protein-coupled receptor CCR2 but has also been described to mediate its
      effects independently of this receptor in vitro and in vivo. Emerging pieces of
      evidence indicate that the CCL2/CCR2 axis is involved in fibrotic diseases, such
      as increased plasma levels of CCL2 and the presence of CCL2-hyperresponsive
      fibroblasts explanted from patients with systemic sclerosis and idiopathic
      pulmonary fibrosis. One of the profibrotic key mediators is the myofibroblast
      characterized by overexpression of alpha-smooth muscle actin and collagen I.
      However, the correlation between the CCL2/CCR2 axis and the activation of
      fibroblasts is not yet fully understood. We have screened human fibroblasts of
      various origins, human pulmonary fibroblasts (HPF), human fetal lung fibroblasts
      (HFL-1) and primary preadipocytes (SPF-1) in regard to CCL2 stimulated fibrotic
      responses. Surprisingly we found that CCL2 mediates anti-fibrotic effects
      independently of CCR2 in human fibroblasts of different origins. 

PMID- 24583147
TI  - (5-Hydroxy-4-oxo-4H-pyran-2-yl)methyl 6-hydroxynaphthalene-2-carboxylate, a kojic
      acid derivative, inhibits inflammatory mediator production via the suppression of
      Syk/Src and NF-kappaB activation.
AB  - Numerous derivatives of kojic acid have been synthesised to expand its
      immunopharmacological uses. Kojic acid is known to have anti-cancer, anti
      inflammatory, and anti-melanogenesis effects. We found that (5-hydroxy-4-oxo-4H
      pyran-2-yl)methyl 6-hydroxynaphthalene-2-carboxylate (MHNC) strongly suppressed
      the production of nitric oxide (NO) in an initial screening experiment. In this
      study, we explored the in vitro and in vivo anti-inflammatory activity of MHNC
      and its inhibitory mechanisms using lipopolysaccharide (LPS)-treated RAW264.7
      cells and HCl/EtOH-treated ICR mice. MHNC dose-dependently diminished the
      secretion of nitric oxide (NO) and prostaglandin (PG)E2 in LPS-treated RAW264.7
      cells. This compound also suppressed the upregulation of mRNA levels for the
      inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 genes. Additionally, the
      transcriptional activation of these genes was inhibited by MHNC through the
      suppression of the nuclear translocation of nuclear factor (NF)-kappaB subunits
      (p65 and p50), as determined by a luciferase reporter assay. Interestingly, MHNC
      treatment was found to suppress a series of upstream signalling cascades
      consisting of IkappaBalpha, AKT, PDK1, Src, and Syk for NF-kappaB activation.
      Furthermore, a direct enzyme assay with purified Src and Syk and luciferase
      assays using Src and Syk overexpression indicated that these enzymes were
      directly inhibited by MHNC. Finally, MHNC (20mg/kg) prevented inflammatory
      symptoms of the stomach in mice treated with HCl/EtOH by reducing phospho
      IkappaBalpha levels. Taken together, our data suggest that MHNC may negatively
      modulate in vitro and in vivo inflammatory responses via the direct suppression
      of Syk/Src and NF-kappaB. 

PMID- 24583148
TI  - Hemin inhibits NLRP3 inflammasome activation in sepsis-induced acute lung injury,
      involving heme oxygenase-1.
AB  - NLRP3 inflammasome activation contributes to acute lung injury (ALI),
      accelerating caspase-1 maturation, and resulting in IL-1beta and IL-18 over
      production. Heme oxygenase-1 (HO-1) plays a protective role in ALI. This study
      investigated the effect of hemin (a potent HO-1 inducer) on NLRP3 inflammasome in
      sepsis-induced ALI. The sepsis model of cecal ligation and puncture (CLP) was
      used in C57BL6 mice. In vivo induction and suppression of HO-1 were performed by
      pretreatment with hemin and zinc protoporphyrin IX (ZnPP, a HO-1 competitive
      inhibitor) respectively. CLP triggered significant pulmonary damage, neutrophil
      infiltration, increased levels of IL-1beta and IL-18, and edema formation in the
      lung. Hemin pretreatment exerted inhibitory effect on lung injury and attenuated
      IL-1beta and IL-18 secretion in serum and lung tissue. In lung tissues, hemin
      down-regulated mRNA and protein levels of NLRP3, ASC and caspase-1. Moreover,
      hemin reduced malondialdehyde and reactive oxygen species production, and
      inhibited NF-kappaB and NLRP3 inflammasome activity. Meanwhile, hemin
      significantly increased HO-1 mRNA and protein expression and HO-1 enzymatic
      activity. In contrast, no significant differences were observed between the CLP
      and ZnPP groups. Our study suggests that hemin-inhibited NLRP3 inflammasome
      activation involved HO-1, reducing IL-1beta and IL-18 secretion and limiting the
      inflammatory response. 

PMID- 24583149
TI  - Identification of erythropoietin receptor-derived peptides having the potential
      to induce cancer-reactive cytotoxic T lymphocytes from HLA-A24(+) patients with
      renal cell carcinoma.
AB  - Molecular targeting therapy with anti-angiogenic agents, including sunitinib and
      sorafenib, has been proven to be the first- and second-line standard treatments
      for metastatic renal cell carcinoma (mRCC) worldwide. Despite their significant
      antitumor effects, most of the patients with mRCC have not been cured. Under such
      circumstances, anti-cancer immunotherapy has been considered as a promising
      treatment modality for mRCC, and cytotoxic T lymphocytes (CTLs) are the most
      powerful effectors among several immune cells and molecules. Therefore, we
      previously conducted anti-cancer vaccine therapy with peptides derived from
      carbonic anhydrase-9 and vascular endothelial growth factor receptor-1 as phase
      I/II trials for mRCC patients and reported their clinical benefits.
      Alternatively, up-regulated expression of erythropoietin (Epo) and its receptor
      (EpoR) in RCC has been reported, and their co-expression is involved in
      tumorigenesis. In order to increase options for peptide-based vaccination
      therapy, we searched for novel EpoR-peptides for HLA-A24(+) RCC patients. Among 5
      peptides derived from EpoR, which were prepared based on the binding motif to the
      HLA-A24 allele, EpoR52-60 peptide had the potential to induce peptide-specific
      CTLs from peripheral blood mononuclear cells of HLA-A24(+) RCC patients.
      Cytotoxicity toward HLA-A24(+) and EpoR-expressing RCC cells was ascribed to
      peptide-specific CD8(+) T cells. These results indicate that the EpoR52-60
      peptide could be a promising candidate for a peptide-based anti-cancer vaccine
      for HLA-A24(+) mRCC patients. 

PMID- 24583150
TI  - A higher frequency of peripheral blood activated B cells in patients with non
      traumatic osteonecrosis of the femoral head.
AB  - OBJECTIVES: B cells play important roles in inflammatory diseases. This study was
      aimed at examining the frequency of different subsets of B cells in patients with
      non-traumatic osteonecrosis of the femoral head (NONFH). METHODS: The percentages
      of the different subsets of circulating B cells in 28 patients with steroid
      related, alcohol-related, or idiopathic NONFH and 10 healthy controls (HC) were
      examined by flow cytometry. The concentrations of serum C-reactive protein (CRP),
      fibrinogen (FIB), immunoglobulins, cytokines and blood erythrocyte sedimentation
      rate (ESR) were measured. RESULTS: In comparison with those in the HC,
      significantly higher percentages of CD27-, CD86+, CD95+, and CD27+CD95+CD19+ but
      lower CD27+CD19+ B cells were detected in the patients. The percentages of CD86+,
      CD95+, and CD27+CD95+CD19+ B cells in each group of the patients were
      significantly higher than those in the HC. The levels of serum IL-17A and IFN
      gamma in steroid group and serum TNF-alpha in alcoholic group were significantly
      higher than those in the HC. The percentages of CD86+CD19+ B cells were
      positively associated with the degrees of femoral head collapse in both steroid
      and alcoholic groups of patients and the levels of serum TNF-alpha were
      positively associated with the degrees of femoral head collapse in the alcoholic
      NONFH patients. CONCLUSIONS: These data suggest a higher frequency of CD86+CD19+
      activated B cells and elevated levels of serum TNF-alpha may be associated with
      the development of NONFH.

PMID- 24583151
TI  - Peritoneal ink tattoos.

PMID- 24583152
TI  - Thymol inhibits Staphylococcus aureus internalization into bovine mammary
      epithelial cells by inhibiting NF-kappaB activation.
AB  - Bovine mastitis is one of the most costly and prevalent diseases in the dairy
      industry and is characterised by inflammatory and infectious processes.
      Staphylococcus aureus (S. aureus), a Gram-positive organism, is a frequent cause
      of subclinical, chronic mastitis. Thymol, a monocyclic monoterpene compound
      isolated from Thymus vulgaris, has been reported to have antibacterial
      properties. However, the effect of thymol on S. aureus internalization into
      bovine mammary epithelial cells (bMEC) has not been investigated. In this study,
      we evaluated the effect of thymol on S. aureus internalization into bMEC, the
      expression of tracheal antimicrobial peptide (TAP) and beta-defensin (BNBD5), and
      the inhibition of NF-kappaB activation in bMEC infected with S. aureus. Our
      results showed that thymol (16-64 MUg/ml) could reduce the internalization of S.
      aureus into bMEC and down-regulate the mRNA expression of TAP and BNBD5 in bMEC
      infected with S. aureus. In addition, thymol was found to inhibit S. aureus
      induced nitric oxide (NO) production in bMEC and suppress S. aureus-induced NF
      kappaB activation in a dose-dependent manner. In conclusion, these results
      indicated that thymol inhibits S. aureus internalization into bMEC by inhibiting
      NF-kappaB activation.

PMID- 24583153
TI  - Immunohistochemical analysis of the expression of TNF-alpha, TGF-beta, and
      caspase-3 in subcutaneous tissue of patients with HIV lipodystrophy syndrome.
AB  - INTRODUCTION: HIV Lipodystrophy Syndrome (HIVLS) is a multifactorial clinical
      expression that presents alterations in the metabolism and distribution pattern
      of body fat via immunological changes capable of disrupting homeostasis. This
      study aimed to analyze the degree of inflammatory, anti-inflammatory, and
      apoptosis activity in the subcutaneous tissue of patients, based on the
      expression of Tumor Necrosis Factor-alpha (TNF-alpha), Transforming Growth Factor
      beta (TGF-beta), and caspase-3, respectively, and correlate them with clinical
      data and with each other. METHODS: This is a cross-analytical study. The biopsy
      of subcutaneous cellular tissue was performed on the right thigh of 19 patients
      with HIVLS who were attended to at a university hospital, and four people without
      HIV and lipodystrophy, for comparison. The type of lipodystrophy and the
      estimation of body fat were obtained during the consultation or obtained from
      medical charts. The cytokine expression was observed in the adipose tissue
      through the streptavidin-biotin peroxidase method, and analyzed by optical
      microscopy. RESULTS: Despite the mixed clinical form having been prevalent in
      both genders, men were more lipoatrophic and women were more lipohypertrophic.
      Men showed higher expression of TNF-alpha and caspase-3 than women. Patients with
      lipodystrophy had higher expression of TNF-alpha and caspase-3 and lower TGF
      beta, compared to the control group. The percentage of body fat was negatively
      correlated with the expression of TNF-alpha and caspase-3. Longer durations of
      infection and use of antiretroviral therapy (ARVT) were positively associated
      with the levels of TNF-alpha. The expression of caspase-3 and TGF-beta was
      associated with higher levels of TNF-alpha. CONCLUSION: Regardless of the
      clinical form, HIVLS is characterized by a chronic inflammatory process
      associated with the male gender, the percentage of body fat, and lipoatrophy
      manifestations. There is increased apoptotic activity in more inflamed tissues
      and there is correlation between TNF-alpha and TGF-beta, which suggests a
      possible negative feedback mechanism between the inflammatory and anti
      inflammatory activity.

PMID- 24583154
TI  - Intra-peritoneal and intra-rectal immunogenicity induced by rotavirus virus like
      particles 2/6/7 in mice.
AB  - We previously developed virus like particles of rotavirus (RV) with VP2, VP6, and
      VP7 proteins (VLP2/6/7) using stable High-five cell line. To evaluate the
      immunogenicity of our construct, we assessed the humoral and cytokine responses
      induced by VLP2/6/7 in BALB/c mice immunized intra-peritoneally and intra
      rectally. Enzyme-linked immunosorbent assay (ELISA) and Relative quantitative
      (RQ) Real-time PCR were used to evaluate the antibody (IgG and IgA) levels in
      serum and mRNA levels of IL-6, IL-10 and IFN-gamma in spleen cells, respectively.
      Our results showed that VLP2/6/7 is capable of intra-peritoneal (I.P.) and intra
      rectal (I.R.) induction of serum IgG and IgA responses. IgA was detected in fecal
      samples of immunization groups by I.P. and I.R. routes. Interestingly, I.R. route
      induced higher IgA titer compared with I.P. route which was statistically
      significant. Moreover, mRNA levels of IL-6 and IFN-gamma were significantly
      elevated in mice immunized intra-peritoneally with VLP2/6/7 compared to control
      group. As such, the mean change was 7.4 (P < 0.05) and 14.8 (P < 0.001) for IFN
      gamma and IL-6, respectively. Likewise, the same pattern was found when mice were
      immunized intra-rectally. Although elevated, the difference in the mean change
      for IL-10 was not statistically significant when compared to control group. Our
      findings indicated that VLPs constructed via a stable insect cell line are able
      to induce both humoral and cellular responses, a similar pattern as observed
      after immunization with live RVs. 

PMID- 24583156
TI  - Determining anti-betanodavirus compounds through a GF-1 cell-based screening
      platform.
AB  - Betanodavirus is a highly contagious pathogen, responsible for severe losses
      incurred in the aquaculture industry. Currently, there are no commercially
      available antivirals against the virulence observed during very early stages of
      fish larvae development. Therefore, we developed a novel GF-1 (grouper fin cell)
      cell viability-based screening assay to facilitate the discovery of an anti
      betanodavirus agent. The assay conditions were optimized and the robustness of
      the assay was confirmed by a Z' factor value ranging from 0.7 to 0.94. After
      screening a library of 2000 small molecule compounds, 43 compounds with a virus
      inhibition capacity of ?55% were identified. A cytochrome P450 inhibitor,
      proadifen hydrochloride, was validated with an EC50 value of 6.48MUM and a CC50
      value of 20.63MUM. This compound inhibited the amplification of viral RNA by
      99.68% 5days post-infection. Surprisingly, we found that 18 of 43 compounds act
      as neurotransmitter agents. These findings indicate a novel way of investigating
      the infection mechanism of betanodavirus, and suggest potential candidates for an
      anti-betanodavirus drug. 

PMID- 24583155
TI  - Impact of mechanical activation, scar, and electrical timing on cardiac
      resynchronization therapy response and clinical outcomes.
AB  - OBJECTIVES: Using cardiac magnetic resonance (CMR), we sought to evaluate the
      relative influences of mechanical, electrical, and scar properties at the left
      ventricular lead position (LVLP) on cardiac resynchronization therapy (CRT)
      response and clinical events. BACKGROUND: CMR cine displacement encoding with
      stimulated echoes (DENSE) provides high-quality strain for overall dyssynchrony
      (circumferential uniformity ratio estimate [CURE] 0 to 1) and timing of onset of
      circumferential contraction at the LVLP. CMR DENSE, late gadolinium enhancement,
      and electrical timing together could improve upon other imaging modalities for
      evaluating the optimal LVLP. METHODS: Patients had complete CMR studies and
      echocardiography before CRT. CRT response was defined as a 15% reduction in left
      ventricular end-systolic volume. Electrical activation was assessed as the time
      from QRS onset to LVLP electrogram (QLV). Patients were then followed for
      clinical events. RESULTS: In 75 patients, multivariable logistic modeling
      accurately identified the 40 patients (53%) with CRT response (area under the
      curve: 0.95 [p < 0.0001]) based on CURE (odds ratio [OR]: 2.59/0.1 decrease),
      delayed circumferential contraction onset at LVLP (OR: 6.55), absent LVLP scar
      (OR: 14.9), and QLV (OR: 1.31/10 ms increase). The 33% of patients with CURE
      <0.70, absence of LVLP scar, and delayed LVLP contraction onset had a 100%
      response rate, whereas those with CURE >=0.70 had a 0% CRT response rate and a 12
      fold increased risk of death; the remaining patients had a mixed response
      profile. CONCLUSIONS: Mechanical, electrical, and scar properties at the LVLP
      together with CMR mechanical dyssynchrony are strongly associated with
      echocardiographic CRT response and clinical events after CRT. Modeling these
      findings holds promise for improving CRT outcomes.

PMID- 24583157
TI  - Nucleoside analogues alone or combined with vaccination prevent hepadnavirus
      viremia and induce protective immunity: alternative strategy for hepatitis B
      virus post-exposure prophylaxis.
AB  - OBJECTIVES: The current strategies for hepatitis B virus (HBV) post-exposure
      prophylaxis (PEP) are not generally available in remote and rural areas of
      developing countries and/or carry potential risks for infection with blood-borne
      transmitted pathogens. Nucleotide analogues (NAs) are successfully used for human
      immunodeficiency virus PEP, and maybe effective for HBV PEP. In this study, we
      tested the NA-based strategies for HBV PEP using the Chinese woodchuck model.
      METHODS: Chinese woodchucks were inoculated intravenously with different doses of
      woodchuck hepatitis virus (WHV). A deoxyguanosine analogue entacavir (ETV), a DNA
      vaccine pWHcIm, or ETV plus pWHcIm were applied to the infected animals 24h
      later. Twenty weeks later, the animals were re-challenged with WHV to test for
      the presence of immunity against WHV. RESULTS: Inoculation with different WHV
      doses had a strong influence on the course of WHV infection; NA alone or in
      combination with a DNA vaccine completely prevented viremia after a high dose of
      WHV inoculation in Chinese woodchucks and induced partial or complete protective
      immunity, respectively. CONCLUSIONS: NA-based PEP strategies (NA alone or in
      combination with vaccine) may be an alternative of HBV PEP, especially in those
      living in the remote and rural areas of the developing countries and the non
      responders to the current vaccine, and may be valuable in the PEP of HBV and HIV
      co-infection after occupational and non-occupational exposure. Further clinical
      studies are warranted to confirm the valuable of NA-based strategies in HBV PEP.

PMID- 24583158
TI  - Oseltamivir-zanamivir combination therapy is not superior to zanamivir
      monotherapy in mice infected with influenza A(H3N2) and A(H1N1)pdm09 viruses.
AB  - The efficacy of oseltamivir-zanamivir combination therapy compared to that of
      monotherapy was evaluated in mice infected with influenza A(H3N2) or A(H1N1)pdm09
      viruses. For A(H3N2) virus, zanamivir monotherapy and oseltamivir-zanamivir
      combination showed significant reduction of mean weight loss compared to
      oseltamivir. Zanamivir monotherapy also conferred decreased mortality, weight
      loss and lung viral titers (LVT) compared to oseltamivir for A(H1N1)pdm09 wild
      type virus. Intermediate benefits were observed for the oseltamivir-zanamivir
      combination. For the oseltamivir-resistant A(H1N1)pdm09 H275Y virus, the efficacy
      of oseltamivir-zanamivir was comparable to that of zanamivir and significantly
      higher than that of oseltamivir in terms of survival, weight loss and LVT. 

PMID- 24583159
TI  - Electrochemical and surface analyses of nanostructured Ti-24Nb-4Zr-8Sn alloys in
      simulated body solution.
AB  - The use of nanostructuring to improve the stability of passive thin films on
      biomaterials can enhance their effectiveness in corrosion resistance and reduce
      the release of ions. The thickness of the ultrathin films that cover Ti and Ti
      alloys (only several nanometers) has prevented researchers from establishing
      systematic methods for their characterization. This study employed a
      multifunctional biomedical titanium alloy Ti-24Nb-4Zr-8Sn (wt.%) as a model
      material. Coarse-grained (CG) and nanostructured (NS) alloys were analyzed in
      0.9% NaCl solution at 37 degrees C. To reveal the details of the passive film, a
      method of sample preparation producing a passive layer suitable for transmission
      electron microscope analysis was developed. Electrochemical corrosion behavior
      was evaluated by potentiodynamic polarization tests and Mott-Schottky
      measurements. Surface depth chemical profile and morphology evolution were
      performed by X-ray photoelectron spectroscopy and in situ atomic force
      microscopy, respectively. A mechanism was proposed on the basis of the point
      defect model to compare the corrosion resistance of the passive film on NS and CG
      alloys. Results showed that the protective amorphous film on NS alloy is thicker,
      denser and more homogeneous with fewer defects than that on CG alloy. The film on
      NS alloy contains more oxygen and corrosion-resistant elements (Ti and Nb), as
      well as their suboxides, compared with the film on CG alloy. These
      characteristics can be attributed to the rapid, uniform growth of the passive
      film facilitated by nanostructuring.

PMID- 24583160
TI  - Revised Gleason grading system is a better predictor of indolent prostate cancer
      at the time of diagnosis: retrospective clinical-pathological study on matched
      biopsy and radical prostatectomy specimens.
AB  - INTRODUCTION/BACKGROUND: The increase of prostate cancer diagnosis after the
      introduction of prostate-specific antigen (PSA) screening resulted in
      overtreatment of patients with low risk tumors. The histological Gleason score
      (GS) revised in 2005 by the International Society of Urological Pathology (ISUP)
      is currently the most reliable tool to separate aggressive from indolent prostate
      cancer. MATERIALS AND METHODS: Using the new 2005 GS criteria we retrospectively
      evaluated biopsy and surgical samples of 1344 patients who underwent radical
      prostatectomy in our institution. According to the new GS criteria we then
      selected 134 patients who would have been suitable for active surveillance at the
      time of biopsy (at least 2 positive cores, PSA < 10 ng/mL, GS <= 6). We finally
      assessed the accuracy of the revised GS in biopsy to predict indolent cancer in
      the prostatectomy specimens. RESULTS: The mean GS increased from 6 to 7 after
      histological revision in biopsy and prostatectomy specimens. Histological
      revision determined a significant decrease of patients with GS <= 6 and an
      increase of those with GS >= 7 (all P < .001). The average of pathologically
      indolent disease (organ-confined, GS <= 6 at surgery, tumor of any volume)
      significantly decreased after histological revision (P < .001). CONCLUSION: The
      revised ISUP 2005 criteria for Gleason grading provided better stratification of
      GS <= 6 prostate cancer and improved the accuracy for the histological diagnosis
      of indolent prostate cancer in biopsy and radical prostatectomy specimens.

PMID- 24583161
TI  - Abiraterone--what is wrong with the adrenal glands?

PMID- 24583162
TI  - Bevacizumab as first-line therapy for patients with brain metastases from renal
      carcinoma: a case series.

PMID- 24583163
TI  - Karyotypically distinct U251, U373, and SNB19 glioma cell lines are of the same
      origin but have different drug treatment sensitivities.

PMID- 24583164
TI  - Identification of an estrogen receptor gene in the natural freshwater snail
      Bithynia tentaculata.
AB  - Mollusks have received increasing interest in ecotoxicological studies but so far
      the available scientific analyses of how their genes are affected by
      anthropogenic pollutants are scarce. The focus of this study is to identify an
      estrogen receptor (er) gene in the common prosobranch snail Bithynia tentaculata
      and to test a hypothesis that 17alpha-Ethinylestradiol (EE2) will modulate er
      gene expression after short-term exposure. We set up exposure experiments with a
      total of 144 snails, which were collected from a natural population in southern
      Sweden. Snails were exposed to either 10ng/L or 100ng/L EE2 during 24h and/or
      72h. From the isolated B. tentaculata RNA we successfully identified and
      characterized a novel er gene and phylogenetic analyses strongly indicate that
      the Bithynia er gene is an ortholog to the human ERalpha (ESR1, NR3A1). We found
      a significant interaction between EE2-dose and exposure duration on the er's gene
      expression (Two-way ANOVA; p=0.04). We also found a significant difference in the
      gene expression of the er when comparing the control and 100ng/L treatment groups
      after 72h in female snails (One-way ANOVA; p=0.047). The results from this study
      should be useful for future field-related studies of estrogen receptors in
      natural populations of mollusks. 

PMID- 24583165
TI  - CFTR genotype and clinical outcomes of adult patients carried as cystic fibrosis
      disease.
AB  - BACKGROUND: There are nearly 2000 cystic fibrosis transmembrane regulator (CFTR)
      mutations that cause cystic fibrosis (CF). These mutations are classified into
      six classes; on the one hand, the first three classes cause severe disease
      involvement in early childhood, on the other hand, the Class IV, V and VI
      mutations cause minor severe disease in the same age. Nowadays, with therapeutic
      advances in CF management and competence of pediatricians, physicians of adults
      have to deal with two groups of CF patients: (i) adults diagnosed in childhood
      with severe mutations and (ii) adults who initiated symptoms in adulthood and
      with Class IV, V and VI mutations. The aim of this study was to analyze adults
      from a clinical center, treated as CF disease, screening the CFTR genotype and
      evaluating the clinical characteristics. METHODS: Thirty patients followed as CF
      disease at the University Hospital were enrolled. After a complete molecular CFTR
      negative screening and sweat test levels between 40 and 59mEq/L, five patients
      were characterized as non-CF disease and were excluded. Molecular screening was
      performed by CFTR gene sequencing/MLPA or by specific mutation screening.
      Clinical data was obtained from medical records. The patients were divided into
      three groups: (1) patients with Class I, II and III mutations in two CFTR
      alleles; (2) genotype with at least one allele of Class IV, V or VI CFTR
      mutations and, (3) non-identified CFTR mutation+one patient with one allele with
      CFTR mutation screened (Class I). RESULTS: There was an association of CFTR class
      mutation and sodium/chloride concentration in the sweat test (sodium: p=0.040;
      chloride: p=0.016), onset of digestive symptoms (p=0.012), lung function
      parameter (SpO2 - p=0.016), Bhalla score (p=0.021), age at diagnosis (p=0.008)
      and CF-related diabetes (p=0.029). There was an association between Pseudomonas
      aeruginosa chronic colonization (as clinical marker for the lung disease status)
      and lung impairment (FEV1% - p=0.027; Bhalla score - p=0.021), CF-related
      diabetes (p=0.040), chloride concentration in the sweat test (p=0.040) and
      chronic infection by microorganisms (Staphylococcus aureus - p=0.039; mucoid P.
      aeruginosa - p=0.001). There is no positive association with the status of other
      clinical markers and the CFTR genotype groups. For clinical association with
      pancreatic insufficiency (as clinical marker for digestive symptoms), no
      association was related. CONCLUSION: The adults with CF diagnosed by sweat test
      have specific clinical and genotypic characteristics, being a population that
      should be studied to cause better future management. Some patients treated as CF
      disease by clinical symptoms, showed no disease, taking into account the sweat
      test and complete exon sequencing/MLPA screening.

PMID- 24583166
TI  - The evolution and functional divergence of the beta-carotene oxygenase gene
      family in teleost fish--exemplified by Atlantic salmon.
AB  - In mammals, two carotenoid cleaving oxygenases are known; beta-carotene 15,15'
      monooxygenase (BCMO1) and beta-carotene 9',10'-oxygenase (BCO2). BCMO1 is a key
      enzyme in vitamin A synthesis by symmetrically cleaving beta-carotene into 2
      molecules of all-trans-retinal, while BCO2 is responsible for asymmetric cleavage
      of a broader range of carotenoids. Here, we show that the Atlantic salmon beta
      carotene oxygenase (bco) gene family contains 5 members, three bco2 and two bcmo1
      paralogs. Using public sequence databases, multiple bco genes were also found in
      several additional teleost species. Phylogenetic analysis indicates that bco2a
      and bco2b originate from the teleost fish specific genome duplication (FSGD or
      3R), while the third and more distant paralog, bco2 like, might stem from a prior
      duplication event in the teleost lineage. The two bcmo1 paralogs (bcmo1 and bcmo1
      like) appear to be the result of an ancient duplication event that took place
      before the divergence of ray-finned (Actinopterygii) and lobe-finned fish
      (Sarcopterygii), with subsequent nonfunctionalization and loss of one
      Sarcopterygii paralog. Gene expression analysis of the bcmo1 and bco2 paralogs in
      Atlantic salmon reveals regulatory divergence with tissue specific expression
      profiles, suggesting that the beta-carotene oxygenase subtypes have evolved
      functional divergences. We suggest that teleost fish have evolved and maintained
      an extended repertoire of beta-carotene oxygenases compared to the investigated
      Sarcopterygii species, and hypothesize that the main driver behind this
      functional divergence is the exposure to a diverse set of carotenoids in the
      aquatic environment.

PMID- 24583167
TI  - The effect of leader peptide mutations on the biological function of bovine
      myostatin gene.
AB  - The growth of muscle fibers can be negatively regulated by bovine myostatin. The
      first two exons of myostatin gene code for the N-propeptide and its third exon
      codes for the C-polypeptide. Myostatin is secreted as a latent configuration
      formed by dimerization of two matured C peptides non-covalently linked with the N
      terminal pro-peptide. Pro-peptide has two distinct functions in guiding protein
      folding and regulating biological activity of myostatin. When the structure of
      the leader peptide is altered via mutations resulting in more tight binding with
      the mature peptide, myostatin function is inhibited, resulting in the changes of
      P21 and CDK2 expression levels which are related to the regulation of cell cycle.
      In the present study, the coding region of bMSTN (bovine myostatin) gene was
      amplified and mutated (A224C and G938A) through fusion PCR, and the mutated bMSTN
      gene (bMSTN-mut) was inserted in frame into the pEF1a-IRES-DsRed-Express2 vector
      and transfected into bovine fibroblast cells. The expression levels of bMSTN-mut,
      P21 and CDK2 (cyclin dependent kinase 2) were examined with qPCR and Western
      blotting. Changes in cell cycle after transfection were also analyzed with flow
      cytometry. The results indicated that leader peptide mutation resulted in down
      regulation of P21 expression levels and up-regulation of CDK2 expression levels.
      The flow cytometry results showed that the proportion of cells in the G0/G1-phase
      was lower and that of cells in the S-phase was higher in bMSTN-mut transfected
      group than that in the control group. The proliferation rate of bMSTN-mut
      transfected cells was also significantly higher than that of the control cells.
      In conclusion, the studies have shown that the pEF1a-IRES-DsRed-Express2-bMSTN
      mut recombinant plasmid could effectively promote the proliferation of bovine
      fibroblast cells. The site-directed mutagenesis of bMSTN gene leader peptide and
      in vitro expression in bovine fibroblast cells could be helpful to further the
      studies of bMSTN in regulating bovine muscle cell growth and development.

PMID- 24583168
TI  - The absence of TERT promoter mutations in primary gastric cancer.

PMID- 24583169
TI  - Next generation sequencing based development of intron-targeting markers in
      tetraploid potato and their transferability to other Solanum species.
AB  - Intron-targeting (IT) markers were developed from next generation sequencing
      (NGS) derived transcript sequencing data from the potato cultivar White Lady. The
      applicability of the IT markers was analyzed in other potato genotypes, and their
      transferability was studied in other Solanum species: section Archaesolanum (5
      species), sect. Solanum (6 species) and a Solanum nigrum population (11
      genotypes). Out of 250 randomly chosen transcript sequences, 144 intron harboring
      loci could be identified for which primer pairs were designed on exons flanking
      the putative introns. The usefulness of the IT primers was experimentally
      analyzed on a subset of 40 randomly chosen loci. Statistical analysis of
      diversity parameters was performed using the ATETRA and POPGENE software
      packages. By localizing the detected 17 polymorphic loci 11 of the 12 potato
      chromosomes could be identified. Specificity of the designed IT primers was
      tested by sequence analysis of amplified IT fragments in a randomly chosen locus.
      The results revealed the efficiency of NGS derived IT marker development and
      indicated their utility in diverse molecular analyses including their
      applicability for cross-species studies. 

PMID- 24583170
TI  - Regulation of sheep alpha-TTP by dietary vitamin E and preparation of monoclonal
      antibody for sheep alpha-TTP.
AB  - alpha-Tocopherol transfer protein (alpha-TTP) is a cytosolic protein that plays
      an important role in regulating concentrations of plasma alpha-tocopherol (the
      most bio-active form of vitamin E). Despite the central roles that alpha-TTP
      plays in maintaining vitamin E adequacy, we have only recently proved the
      existence of the alpha-TTP gene in sheep and, for the first time, cloned its full
      length cDNA. However, the study of sheep alpha-TTP is still in its infancy. In
      the present study, thirty-five local male lambs of Tan sheep with similar initial
      body weight were randomly divided into five groups and fed with diets
      supplemented with 0 (control group), 20, 100, 200, 2000IU.sheep(-1).d(-1) vitamin
      E for 120 days. At the end of the experiment, the plasma and liver vitamin E
      contents were analyzed first and then alpha-TTP mRNA and protein expression
      levels were determined by quantitative real-time PCR (qRT-PCR) and Western-blot
      analysis, respectively. In addition, as no sheep alpha-TTP antibody was
      available, a specific monoclonal antibody (McAb) against the ovine alpha-TTP
      protein was prepared. The effect of vitamin E supplementation was confirmed by
      the significant changes in the concentrations of vitamin E in the plasma and
      liver. As shown by qRT-PCR and Western-blot analysis, dietary vitamin E does not
      affect sheep alpha-TTP gene expression, except for high levels of vitamin E
      supplementation, which significantly increased expression at the protein level.
      Importantly, the specific sheep anti-alpha-TTP McAb we generated could provide
      optimal recognition in ELISA, Western-blot and immunohistochemistry assays, which
      will be a powerful tool in future studies of the biological functions of sheep
      alpha-TTP.

PMID- 24583171
TI  - Identification, expression pattern, cellular location and potential role of the
      caveolin-1 gene from Artemia sinica.
AB  - Caveolins are integral membrane proteins that serve as scaffolds to recruit
      numerous signaling molecules. Caveolins play an important role in membrane
      trafficking, signal transduction, substrate transport and endocytosis in
      differentiated cells. In this study, a caveolin-1 gene from Artemia sinica (As
      cav-1) was successfully cloned for the first time. The full-length cDNA of As-cav
      1 comprises 974 bp, with a 675 bp open reading frame (ORF) that encodes a
      polypeptide of 224 amino acids with a caveolin scaffolding domain (CSD) and two
      transmembrane domains. Multiple sequence alignment revealed that the putative As
      CAV-1 protein sequence was relatively conserved across species, especially in the
      CSD domain. Real-time PCR revealed high levels of the As-cav-1 transcript at 0h
      of embryo development. Furthermore, As-cav-1 transcripts were highly upregulated
      under high salinity (2000/00) and low temperature stresses (15 degrees C). To
      further characterize As-cav-1, recombinant pET30a-cav-1 protein was expressed
      using a prokaryotic expression system. The recombinant protein comprised 290
      amino acids with a theoretical molecular weight of 32kDa, and a predicted
      isoelectric point of 5.6. Western blotting of the expression levels of As-CAV-1
      during different embryo development stages revealed that As-CAV-1 levels
      decreased gradually during development stages from 0 h to 40 h, and increased at
      3d. Furthermore, western blotting showed that As-CAV-1 was upregulated to its
      highest expression level by low temperature stress (15 degrees C) and high
      salinity. Confocal laser microscopy analysis, using antibodies generated against
      the recombinant As-CAV-1 protein, showed that As-CAV-1 was mostly located in the
      cell membrane. Our results suggested that As-cav-1 plays a vital role in
      protecting embryos from high salt damage and low temperature stress, especially
      during post-diapause embryonic development.

PMID- 24583172
TI  - Construction and analysis of gonad suppression subtractive hybridization
      libraries for the rice field eel, Monopterus albus.
AB  - The objective of this study was to investigate gene transcription profiles of the
      stage IV ovary and the ovotestis of the rice field eel (Monopterus albus) in an
      attempt to uncover genes involved in sex reversal and gonad development.
      Suppression subtractive hybridization (SSH) libraries were constructed using mRNA
      from the stage IV ovary and the ovotestis. In total 100 positive clones from the
      libraries were selected at random and sequenced, and then expressed sequence tags
      (ESTs) were used to search against sequences in the GenBank database using the
      BLASTn and BLASTx search algorithms. High quality SSH cDNA libraries and 90 ESTs
      were obtained. Of these ESTs, 43 showed high homology with genes of known
      function and these are associated with energy metabolism, signal transduction,
      transcription regulation and so on. The remaining 47 ESTs shared no homology with
      any genes in GenBank and are thus considered to be hypothetical genes.
      Furthermore, the four genes F11, F63, R11, and R47 from the forward and reverse
      libraries were analyzed in gonad, brain, heart, spleen, liver, kidney and muscle
      tissues. The results showed that the transcription of the F11 and F63 genes was
      significantly increased while the expression of the R11 and R47 genes was
      significantly decreased from IV or V ovary. In addition, the results also
      indicated that the four genes' expression was not gonad-tissue specific. This
      results strongly suggested that they may be involved in the rice field eel gonad
      development and/or sex reversal. 

PMID- 24583173
TI  - Comparative genomic analysis of eutherian Mas-related G protein-coupled receptor
      genes.
AB  - The present study made attempts to update comprehensive eutherian Mas-related G
      protein-coupled receptor gene data sets, using public eutherian genomic sequence
      data sets and new genomics and molecular evolution tests. Among 254 potential
      coding sequences, the most comprehensive gene data set of eutherian Mas-related G
      protein-coupled receptor genes included 119 complete coding sequences that
      described eight major gene clusters. The present analysis integrated gene
      annotations, phylogenetic analysis and protein molecular evolution analysis and
      first explained differential gene expansion patterns of eutherian Mas-related G
      protein-coupled receptor genes. The updated classification and nomenclature of
      eutherian Mas-related G protein-coupled receptor genes were proposed as new
      framework of future experiments. 

PMID- 24583174
TI  - Investigation of the association between ATP2B4 and ATP5B genes with colorectal
      cancer.
AB  - Colorectal cancer (CRC) develops as a multi-step process which results from
      gradual accumulation of mutations in proto-oncogenes, tumor suppressor, and DNA
      repair genes. Mortality rate of CRC is very high. Therefore, development of
      alternative diagnostic methods which can be used in the early diagnosis is
      crucial. ATP2B4 gene encodes one of the four isoforms of p-type ATPase PMCA
      enzyme and bears critical importance in maintaining the balance of intracellular
      calcium homeostasis by providing the export of calcium ions out of the cell.
      ATP5B encodes a subunit of the mitochondrial ATP synthase which is an f-type
      ATPase. In this study, the relationship between ATP2B4 and ATP5B genes and CRC
      regarding gene expression was investigated. Study groups were constructed from a
      number of 50 patients (25 males, 25 females) with the mean age of 55.68 +/- 9.4
      and the gene expression levels in the healthy and cancerous tissues of the
      patients were compared by using semi-quantitative PCR and Real-Time PCR methods.
      As a result, in patients with rectum tumors, there was a significant relationship
      between ATP2B4 gene expression and the tumor location and in patients younger
      than 45 years, ATP5B gene expressions were detected significantly higher in tumor
      tissues by using RT-PCR. However, no significant relationship was detected in
      terms of expression differences of ATP2B4 and ATP5B genes between cancerous and
      healthy tissues of the CRC patients. ATP2B4 and ATP5B genes might have indirect
      associations in CRC pathogenesis and the investigation of their interactions with
      DNA repair and other related genes may help in understanding of CRC formation.

PMID- 24583175
TI  - U1 small nuclear RNA variants differentially form ribonucleoprotein particles in
      vitro.
AB  - The U1 small nuclear (sn)RNA participates in splicing of pre-mRNAs by recognizing
      and binding to 5' splice sites at exon/intron boundaries. U1 snRNAs associate
      with 5' splice sites in the form of ribonucleoprotein particles (snRNPs) that are
      comprised of the U1 snRNA and 10 core components, including U1A, U1-70K, U1C and
      the 'Smith antigen', or Sm, heptamer. The U1 snRNA is highly conserved across a
      wide range of taxa; however, a number of reports have identified the presence of
      expressed U1-like snRNAs in multiple species, including humans. While numerous U1
      like molecules have been shown to be expressed, it is unclear whether these
      variant snRNAs have the capacity to form snRNPs and participate in splicing. The
      purpose of the present study was to further characterize biochemically the
      ability of previously identified human U1-like variants to form snRNPs and bind
      to U1 snRNP proteins. A bioinformatics analysis provided support for the
      existence of multiple expressed variants. In vitro gel shift assays, competition
      assays, and immunoprecipitations (IPs) revealed that the variants formed high
      molecular weight assemblies to varying degrees and associated with core U1 snRNP
      proteins to a lesser extent than the canonical U1 snRNA. Together, these data
      suggest that the human U1 snRNA variants analyzed here are unable to efficiently
      bind U1 snRNP proteins. The current work provides additional biochemical insights
      into the ability of the variants to assemble into snRNPs. 

PMID- 24583176
TI  - Combined genetic mutations have remarkable effect on portal vein thrombosis and
      Budd Chiari syndrome: comment to Simsek, E., Yesilyurt, A., Pinarli, F., et al.,
      combined genetic mutations have remarkable effect on deep venous thrombosis
      and/or pulmonary embolism occurrence, Gene (2013),
      http://dx.doi.org/10.1016/j.gene.2013.11.019.

PMID- 24583177
TI  - Genomic identification and molecular characterization of a non-mammalian
      TNFAIP8L2 gene from Oplegnathus fasciatus.
AB  - Tumor necrosis factor alpha-induced protein 8-like 2 (TNFAIP8L2) is a newly
      described negative immune regulator, whose enigmatic biological functions are not
      clearly understood. In the present study, the TNFAIP8L2 homolog of rock bream
      (Oplegnathus fasciatus) was identified and characterized. The genomic composition
      of rock bream TNFAIP8L2 (~6.7 kb) represented a tripartite arrangement in which
      three exons are interrupted by two introns. The rock bream TNFAIP8L2 transcript
      (1974 bp) possessed a coding sequence of 561 bp encoding a peptide of 186 amino
      acids. The predicted rock bream TNFAIP8L2 protein was 21.1kDa and revealed the
      typical features of known TNFAIP8L2 members including the DED-like domain. Rock
      bream TNFAIP8L2 was composed of six alpha-helices and demonstrated a distinct
      folding pattern of the TNFAIP8L2 family. It showed a certain degree of homology
      and phylogenetic relationship with the corresponding tilapia counterpart. Based
      on an interspecies genomic organizational comparison of TNFAIP8L2 orthologs, they
      could be classified into two classes, with teleost and non-teleost origin
      respectively. While teleost TNFAIP8L2s manifest a tripartite arrangement, non
      teleost counterparts demonstrate a dipartite structure suggesting the loss of an
      intron during the post-piscine speciation. Promoter proximal region of rock bream
      TNFAIP8L2 consisted of multiple immune responsive cis-regulatory elements.
      Analysis of basal transcription in eleven tissues revealed its constitutive
      expression in examined tissues with highest magnitude in the head kidney. The
      modulated temporal mRNA expression of rock bream TNFAIP8L2 in head kidney post
      challenges with stimulants (LPS and poly I:C) and pathogens (Streptococcus iniae
      and irido virus) was stimulant-specific. Additionally, a drastic down-regulation
      of rock bream TNFAIP8L2 mRNA level occurred in blood cells collected from
      experimentally injured animals, and it was accompanied by a contemporaneous down
      regulation of cytokines, TNF-alpha and TGFbeta3. All these findings imply that
      rock bream TNFAIP8L2 is potentially responsible for immune and inflammatory
      modulation in rock bream.

PMID- 24583178
TI  - The complete chloroplast genome sequence of Taxus chinensis var. mairei
      (Taxaceae): loss of an inverted repeat region and comparative analysis with
      related species.
AB  - Taxus chinensis var. mairei (Taxaceae) is a domestic variety of yew species in
      local China. This plant is one of the sources for paclitaxel, which is a
      promising antineoplastic chemotherapy drugs during the last decade. We have
      sequenced the complete nucleotide sequence of the chloroplast (cp) genome of T.
      chinensis var. mairei. The T. chinensis var. mairei cp genome is 129,513 bp in
      length, with 113 single copy genes and two duplicated genes (trnI-CAU, trnQ-UUG).
      Among the 113 single copy genes, 9 are intron-containing. Compared to other land
      plant cp genomes, the T. chinensis var. mairei cp genome has lost one of the
      large inverted repeats (IRs) found in angiosperms, fern, liverwort, and
      gymnosperm such as Cycas revoluta and Ginkgo biloba L. Compared to related
      species, the gene order of T. chinensis var. mairei has a large inversion of
      ~110kb including 91 genes (from rps18 to accD) with gene contents unarranged.
      Repeat analysis identified 48 direct and 2 inverted repeats 30 bp long or longer
      with a sequence identity greater than 90%. Repeated short segments were found in
      genes rps18, rps19 and clpP. Analysis also revealed 22 simple sequence repeat
      (SSR) loci and almost all are composed of A or T.

PMID- 24583179
TI  - The child health implications of privatizing Africa's urban water supply.
AB  - Can private sector participation (PSP) in the piped water sector improve child
      health? I use child-level data from 39 African countries during 1986-2010 to show
      that PSP decreases diarrhea among urban-dwelling, under-five children by 2.6
      percentage points, or 16% of its mean prevalence. Children from the poorest
      households benefit most. PSP is also associated with a 7.8 percentage point
      increase in school attendance of 7-17 year olds. Importantly, PSP increases usage
      of piped water by 9.7 percentage points, suggesting a possible causal channel
      explaining health improvements. To attribute causality, I exploit time-variation
      in the private water market share controlled by African countries' former
      colonizers. A placebo analysis reveals that PSP does not affect respiratory
      illness, nor does it affect a control group of rural children. 

PMID- 24583181
TI  - Immunoaffinity purification of the functional 20S proteasome from human cells via
      transient overexpression of specific proteasome subunits.
AB  - The proteasome is a multi-subunit proteolytic complex that plays a central role
      in protein degradation in all eukaryotic cells. It regulates many vital cellular
      processes therefore its dysfunction can lead to various pathologies including
      cancer and neurodegeneration. Isolation of enzymatically active proteasomes is a
      key step to the successful study of the proteasome regulation and functions. Here
      we describe a simple and efficient protocol for immunoaffinity purification of
      the functional 20S proteasomes from human HEK 293T cells after transient
      overexpression of specific proteasome subunits tagged with 3xFLAG. To construct
      3xFLAG-fusion proteins, DNA sequences encoding the 20S proteasome subunits PSMB5,
      PSMA5, and PSMA3 were cloned into mammalian expression vector pIRES-hrGFP-1a. The
      corresponding recombinant proteins PSMB5-3xFLAG, PSMA5-3xFLAG, or PSMA3-3xFLAG
      were transiently overexpressed in human HEK 293T cells and were shown to be
      partially incorporated into the intact proteasome complexes. 20S proteasomes were
      immunoprecipitated from HEK 293T cell extracts under mild conditions using
      antibodies against FLAG peptide. Isolation of highly purified 20S proteasomes
      were confirmed by SDS-PAGE and Western blotting using antibodies against
      different proteasome subunits. Affinity purified 20S proteasomes were shown to
      possess chymotrypsin- and trypsin-like peptidase activities confirming their
      functionality. This simple single-step affinity method of the 20S proteasome
      purification can be instrumental to subsequent functional studies of proteasomes
      in human cells. 

PMID- 24583180
TI  - Expression, purification and structural properties of ABC transporter ABCA4 and
      its individual domains.
AB  - ABCA4 is a member of the A subfamily of ATP-binding cassette transporters that
      consists of large integral membrane proteins implicated in inherited human
      diseases. ABCA4 assists in the clearance of N-retinylidene
      phosphatidylethanolamine, a potentially toxic by-product of the visual cycle
      formed in photoreceptor cells during light perception. Structural and functional
      studies of this protein have been hindered by its large size, membrane
      association, and domain complexity. Although mammalian, insect and bacterial
      systems have been used for expression of ABCA4 and its individual domains, the
      structural relevance of resulting proteins to the native transporter has yet to
      be established. We produced soluble domains of ABCA4 in Escherichia coli and
      Saccharomyces cerevisiae and the full-length transporter in HEK293 cells.
      Electron microscopy and size exclusion chromatography were used to assess the
      conformational homogeneity and structure of these proteins. We found that
      isolated ABCA4 domains formed large, heterogeneous oligomers cross-linked with
      non-specific disulphide bonds. Incomplete folding of cytoplasmic domain 2 was
      proposed based on fluorescence spectroscopy results. In contrast, full-length
      human ABCA4 produced in mammalian cells was found structurally equivalent to the
      native protein obtained from bovine photoreceptors. These findings offer
      recombinantly expressed full-length ABCA4 as an appropriate object for future
      detailed structural and functional characterization. 

PMID- 24583182
TI  - A novel method for purification of the endogenously expressed fission yeast Set2
      complex.
AB  - Chromatin-associated proteins are heterogeneously and dynamically composed. To
      gain a complete understanding of DNA packaging and basic nuclear functions, it is
      important to generate a comprehensive inventory of these proteins. However,
      biochemical purification of chromatin-associated proteins is difficult and is
      accompanied by concerns over complex stability, protein solubility and yield.
      Here, we describe a new method for optimized purification of the endogenously
      expressed fission yeast Set2 complex, histone H3K36 methyltransferase. Using the
      standard centrifugation procedure for purification, approximately half of the
      Set2 protein separated into the insoluble chromatin pellet fraction, making it
      impossible to recover the large amounts of soluble Set2. To overcome this poor
      recovery, we developed a novel protein purification technique termed the
      filtration/immunoaffinity purification/mass spectrometry (FIM) method, which
      eliminates the need for centrifugation. Using the FIM method, in which whole cell
      lysates were filtered consecutively through eight different pore sizes (53
      0.8MUm), a high yield of soluble FLAG-tagged Set2 was obtained from fission
      yeast. The technique was suitable for affinity purification and produced a low
      background. A mass spectrometry analysis of anti-FLAG immunoprecipitated proteins
      revealed that Rpb1, Rpb2 and Rpb3, which have all been reported previously as
      components of the budding yeast Set2 complex, were isolated from fission yeast
      using the FIM method. In addition, other subunits of RNA polymerase II and its
      phosphatase were also identified. In conclusion, the FIM method is valid for the
      efficient purification of protein complexes that separate into the insoluble
      chromatin pellet fraction during centrifugation. 

PMID- 24583185
TI  - Glucose-induced inhibition of the appetitive brain response to visual food cues
      in polycystic ovary syndrome patients.
AB  - We postulate that insulin regulation of food intake is compromised when insulin
      resistance is present. In order to investigate the effect of insulin sensitivity
      on appetitive brain responses, we conducted functional magnetic resonance imaging
      studies in a group of women diagnosed with polycystic ovary syndrome (PCOS) in
      which insulin sensitivity ranged from normal to resistant. Subjects (n=19) were
      imaged while viewing pictures of high calorie (HC) foods and low calorie (LC)
      foods after ingesting either 75 g glucose or an equivalent volume of water. The
      insulin sensitive group showed reduced blood oxygen level dependent (BOLD) signal
      in response to food pictures following glucose ingestion in numerous
      corticolimbic brain regions, whereas the insulin resistant group did not. There
      was a significant interaction between insulin sensitivity (sensitive vs
      resistant) and condition (water vs glucose). The largest clusters identified
      included the left insula, bilateral limbic/parahippocampal gyrus/culmen/midbrain,
      bilateral limbic lobe/precuneus, and left superior/mid temporal gyrus/parietal
      for HC and LC stimuli combined, the left parahippocampal
      gyrus/fusiform/pulvinar/midbrain for HC pictures, and the left superior/mid
      temporal gyrus/parietal and middle/inferior frontal gyrus/orbitofrontal cortex
      for LC pictures. Furthermore, BOLD signal in the anterior cingulate, medial
      frontal gyrus, posterior cingulate/precuneus, and parietal cortex during a
      glucose challenge correlated negatively with insulin sensitivity. We conclude the
      PCOS women with insulin resistance have an impaired brain response to a glucose
      challenge. The inability of postprandial hyperinsulinemia to inhibit brain
      responsiveness to food cues in insulin resistant subjects may lead to greater non
      homeostatic eating.

PMID- 24583183
TI  - A blood meal-induced Ixodes scapularis tick saliva serpin inhibits trypsin and
      thrombin, and interferes with platelet aggregation and blood clotting.
AB  - Ixodes scapularis is a medically important tick species that transmits causative
      agents of important human tick-borne diseases including borreliosis, anaplasmosis
      and babesiosis. An understanding of how this tick feeds is needed prior to the
      development of novel methods to protect the human population against tick-borne
      disease infections. This study characterizes a blood meal-induced I. scapularis
      (Ixsc) tick saliva serine protease inhibitor (serpin (S)), in-house referred to
      as IxscS-1E1. The hypothesis that ticks use serpins to evade the host's defense
      response to tick feeding is based on the assumption that tick serpins inhibit
      functions of protease mediators of the host's anti-tick defense response. Thus,
      it is significant that consistent with hallmark characteristics of inhibitory
      serpins, Pichia pastoris-expressed recombinant IxscS-1E1 (rIxscS-1E1) can trap
      thrombin and trypsin in SDS- and heat-stable complexes, and reduce the activity
      of the two proteases in a dose-responsive manner. Additionally, rIxscS-1E1 also
      inhibited, but did not apparently form detectable complexes with, cathepsin G and
      factor Xa. Our data also show that rIxscS-1E1 may not inhibit chymotrypsin,
      kallikrein, chymase, plasmin, elastase and papain even at a much higher rIxscS
      1E1 concentration. Native IxscS-1E1 potentially plays a role(s) in facilitating
      I. scapularis tick evasion of the host's hemostatic defense as revealed by the
      ability of rIxscS-1E1 to inhibit adenosine diphosphate- and thrombin-activated
      platelet aggregation, and delay activated partial prothrombin time and thrombin
      time plasma clotting in a dose-responsive manner. We conclude that native IxscS
      1E1 is part of the tick saliva protein complex that mediates its anti-hemostatic,
      and potentially inflammatory, functions by inhibiting the actions of thrombin,
      trypsin and other yet unknown trypsin-like proteases at the tick-host interface.

PMID- 24583184
TI  - Ostertagia ostertagi macrophage migration inhibitory factor is present in all
      developmental stages and may cross-regulate host functions through interaction
      with the host receptor.
AB  - Macrophage migration inhibitory factor (MIF) of Ostertagia ostertagi, an abomasal
      parasite of cattle, was characterised in the present study. Phylogenetic analysis
      identified at least three O. ostertagi MIFs (Oos-MIFs), each encoded by a
      distinct transcript: Oos-MIF-1.1, Oos-MIF-1.2 and Oos-MIF-2. Oos-MIF-2 is only
      distantly related to Oos-MIF-1s, but has higher sequence similarity with the
      Caenorhabditis elegans MIF2. Oos-MIF-1.1 and Oos-MIF-1.2 are similar (93%) and
      thus collectively referred to as Oos-MIF-1 when characterised with immunoassays.
      Recombinant Oos-MIF-1.1 (rOos-MIF-1.1) is catalytically active as a tautomerase.
      A mutation (rOos-MIF-1.1P1G) or duplication of Pro1 residue (rOos-MIF-1.1P1+P)
      resulted in reduced oligomerisation and loss of tautomerase activity. The
      tautomerase activity of rOos-MIF-1.1 was only partially inhibited by ISO-1 but
      was abrogated by a rOos-MIF-1.1-specific antibody. Oos-MIF-1 was detected in all
      developmental stages of O. ostertagi, with higher levels in the adult stage; it
      was also detected in adult worm excretory/secretory product. Oos-MIF-1 was
      localised to the hypodermis/muscle, reproductive tract and intestine, but not to
      the cuticle. rOos-MIF-1.1, but not rOos-MIF-1.1P1G, was able to specifically bind
      to human CD74, a MIF cell surface receptor, with an affinity comparable with
      human MIF. Immunostaining indicated that macrophages were able to internalise
      rOos-MIF-1.1, further supporting receptor-mediated transportation. Herein we also
      show that rOos-MIF-1.1 inhibited migration of bovine macrophages and restored
      glucocorticoid-suppressed, lipopolysaccharide-induced TNF-alpha and IL-8 in human
      and/or bovine macrophages. Given its dual role in self-regulation and molecular
      mimicry, this secreted parasite protein warrants investigation as a vaccine
      candidate against O. ostertagi infections in cattle.

PMID- 24583186
TI  - Mycotoxin exposure in rural residents in northern Nigeria: a pilot study using
      multi-urinary biomarkers.
AB  - A pilot, cross-sectional, correlational study was conducted in eight rural
      communities in northern Nigeria to investigate mycotoxin exposures in 120
      volunteers (19 children, 20 adolescents and 81 adults) using a modern LC-MS/MS
      based multi-biomarker approach. First morning urine samples were analyzed and
      urinary biomarker levels correlated with mycotoxin levels in foods consumed the
      day before urine collection. A total of eight analytes were detected in 61/120
      (50.8%) of studied urine samples, with ochratoxin A, aflatoxin M1 and fumonisin
      B1 being the most frequently occurring biomarkers of exposure. These mycotoxin
      biomarkers were present in samples from all age categories, suggestive of chronic
      (lifetime) exposures. Rough estimates of mycotoxin intake suggested some
      exposures were higher than the tolerable daily intake. Overall, rural consumer
      populations from Nasarawa were more exposed to several mixtures of mycotoxins in
      their diets relative to those from Kaduna as shown by food and urine biomarker
      data. This study has shown that mycotoxin co-exposure may be a major public
      health challenge in rural Nigeria; this calls for urgent intervention. 

PMID- 24583187
TI  - Associations between serum phthalates and biomarkers of reproductive function in
      589 adult men.
AB  - Phthalates which are widely used, are ubiquitous in the environment and in some
      human tissues. It is generally accepted that phthalates exert their toxic action
      by inhibiting Leydig cell synthesis of testosterone, but in vitro studies have
      also shown anti-androgenic effects at the receptor level. Some cross-sectional
      studies have shown inverse associations between urinary levels of phthalates and
      reproductive hormones, but results are conflicting and the evidence base is
      limited. The aim of this study was to investigate if levels of di-2-ethylhexyl
      phthalate (DEHP) and diisononyl phthalate (DiNP) metabolites in serum are
      associated with serum concentrations of male reproductive hormones and semen
      quality. A secondary aim was to investigate metabolic pathways of DEHP and DiNP
      on semen quality and reproductive hormones. A cross-sectional sample of 589
      spouses of pregnant women from Greenland, Poland and Ukraine were enrolled
      between 2002 and 2004. The men gave semen and blood samples and were interviewed.
      Six phthalate metabolites of DEHP and DiNP were measured by liquid chromatography
      tandem mass spectrometry in serum. The metabolites were summed according to their
      molar weight. We observed significant inverse associations between serum levels
      of the metabolites, the proxies and serum testosterone. Negative associations
      were also discovered between some metabolites and sex hormone-binding globulin,
      semen volume and total sperm count. Findings are compatible with a weak anti
      androgenic action of DEHP metabolites, but less so for DiNP metabolites.
      Metabolic pathways differed significantly between the three study sites, but
      without major effect on semen quality or reproductive hormones. 

PMID- 24583189
TI  - Prior exposure to repeated immobilization or chronic unpredictable stress
      protects from some negative sequels of an acute immobilization.
AB  - Exposure to chronic unpredictable stress (CUS) is gaining acceptance as a
      putative animal model of depression. However, there is evidence that chronic
      exposure to stress can offer non-specific stress protection from some effects of
      acute superimposed stressors. We then compared in adult male rats the protection
      afforded by prior exposure to CUS with the one offered by repeated immobilization
      on boards (IMO) regarding some of the negative consequences of an acute exposure
      to IMO. Repeated exposure to IMO protected from the negative consequences of an
      acute IMO on activity in an open-field, saccharin intake and body weight gain.
      Active coping during IMO (struggling) was markedly reduced by repeated exposure
      to the same stressor, but it was not affected by a prior history of CUS,
      suggesting that our CUS protocol does not appear to impair active coping
      responses. CUS exposure itself caused a strong reduction of activity in the open
      field but appeared to protect from the hypo-activity induced by acute IMO.
      Moreover, prior CUS offered partial protection from acute IMO-induced reduction
      of saccharin intake and body weight gain. It can be concluded that a prior
      history of CUS protects from some of the negative consequences of exposure to a
      novel severe stressor, suggesting the development of partial cross-adaptation
      whose precise mechanisms remain to be studied. 

PMID- 24583188
TI  - Role of the kappa-opioid receptor system in stress-induced reinstatement of
      nicotine seeking in rats.
AB  - RATIONALE: The correlation between stress and smoking is well established. The
      mechanisms that underlie this relationship are, however, unclear. Recent data
      suggest that the kappa-opioid system is involved in the mediation of negative
      affective states associated with stress thereby promoting drug addiction and
      relapse. Pharmacological treatments targeting the kappa-opioid system and this
      mechanism may prove to be useful therapeutics for nicotine addiction in the
      future. OBJECTIVES: We sought to determine whether there was a stress-specific
      role of the kappa-opioid system in nicotine seeking behavior. METHOD: Groups of
      male Long Evans rats were trained to self-administer nicotine intravenously;
      their operant responding for nicotine was extinguished prior to tests of
      reinstatement. Pretreatment with systemic injections of the kappa-opioid receptor
      (KOR) antagonist nor-binaltorphimine (nor-BNI) was given prior to tests of stress
      (systemic injections of yohimbine (YOH)) or cue-induced reinstatement of nicotine
      seeking. Systemic injections of the KOR agonist U50,488 were also given in a test
      for reinstatement of nicotine seeking. RESULTS: Nor-BNI pretreatment at 1h and
      24h prior to testing was able to block YOH-induced, but not cue-induced
      reinstatement of nicotine seeking. U50,488 reinstated nicotine seeking behavior
      in a dose-dependent manner. CONCLUSIONS: These findings support the hypothesis
      that the kappa-opioid system is involved in relapse to nicotine seeking induced
      by stress, but not by conditioned cues. KOR antagonists such as nor-BNI may
      therefore be useful novel therapeutic agents for decreasing the risk of stress
      induced drug relapse.

PMID- 24583190
TI  - Relationship between ethanol-induced activity and anxiolysis in the open field,
      elevated plus maze, light-dark box, and ethanol intake in adolescent rats.
AB  - It is yet unclear if ethanol-induced motor stimulation in the open field (OF)
      merely reflects psychomotor stimulating effects of the drug or if this
      stimulation is driven or modulated by ethanol's antianxiety properties. In the
      present study, adolescent rats were administered with different ethanol doses or
      remained untreated. They were sequentially assessed in the OF, elevated plus maze
      (EPM), and light-dark box (LDB) and then assessed for ethanol intake. The aims
      were to assess the relationship between measures of ethanol-induced activity and
      anxiolysis, analyze ethanol intake as a function of prior ethanol exposure, and
      associate behavioral responsiveness in these apparatus with ethanol intake during
      adolescence. The results suggested that the enhanced exploration of the OF
      observed after 2.5 and 3.25 g/kg ethanol reflected a motor-stimulating effect
      that appeared to be relatively independent of anxiolysis. The 1.25 g/kg dose
      induced motor stimulation in the OF and anti-anxiety effects in the EPM, but
      these effects were relatively independent. The 0.5 g/kg ethanol dose exerted
      significant anxiolytic effects in the EPM in the absence of stimulating effects
      in the OF. A multivariate regression analysis indicated that adolescents with a
      higher frequency of rearing behavior in the OF, higher percentage of open arm
      entries in the EPM, and lower propensity to enter the central area of the OF
      exhibited greater ethanol intake. These results indicate that the OF is a valid
      procedure for the measurement of ethanol-induced stimulation, and provide
      information toward characterizing subpopulations of adolescents at risk for
      initiating alcohol drinking.

PMID- 24583191
TI  - Maternal exposure to fluoxetine during gestation and lactation affects the DNA
      methylation programming of rat's offspring: modulation by folic acid
      supplementation.
AB  - Fluoxetine is an antidepressant that has been largely used for treatment of
      depression in pregnancy. In the present study we evaluated the effects of the
      exposure to fluoxetine during gestation and lactation on DNA methylation of rat
      brain regions. Female Wistar rats were treated with 5mg/kg of fluoxetine during
      pregnancy and lactation. In order to assess the effects of fluoxetine in the
      context of maternal folic acid supplementation we performed an additional
      combined treatment composed by folic acid (8 mg/kg/day) and fluoxetine (5
      mg/kg/day). On the postnatal day 22, male rats were euthanized and hippocampus,
      cortex, hypothalamus, and periaqueductal gray area were removed. Global DNA
      methylation was quantified using a high-throughput ELISA-based method.
      Neurofunctional changes were addressed using validated behavioral tests: hot
      plate, elevated plus maze and open field. A decrease in the global DNA
      methylation profile of hippocampus was associated to the exposure to fluoxetine,
      whereas an increase in methylation was observed in cortex. The combined treatment
      induced an increase in the methylation of hippocampus indicating the potential of
      folic acid to modulate this epigenetic alteration. Increase in the latency to the
      thermal nociceptive response was observed in animals exposed to fluoxetine
      whereas this effect was abolished in animals from the combined treatment. In
      summary we demonstrated that exposure to fluoxetine during gestation and
      lactation affect the DNA methylation of brain and the nociceptive response of
      rats. Furthermore our data reveal the potential of folic acid to modulate
      epigenetic and functional changes induced by early exposure to fluoxetine.

PMID- 24583192
TI  - Extended exposure to a palatable cafeteria diet alters gene expression in brain
      regions implicated in reward, and withdrawal from this diet alters gene
      expression in brain regions associated with stress.
AB  - Like people, rodents exposed to energy-rich foods over-eat and become overweight.
      Removal of this diet activates stress systems, which may explain why people have
      difficulty dieting. We exposed rats to energy-rich foods in order to identify
      changes in the brain induced by that diet and by its removal. Sprague Dawley rats
      were fed lab-chow or an energy-rich cafeteria diet (plus chow). Following 6 or 15
      weeks, half of each group was switched to the opposing diet. Rats were culled 48
      h later. We measured fat mass, plasma hormones, and assessed brains for mRNA
      expression of several genes. Cafeteria-fed rats consumed more kilojoules, weighed
      more and had elevated leptin (plus reduced CORT at 15 weeks) relative to chow-fed
      rats. Fifteen weeks of cafeteria diet suppressed MU-opioid and CB1 receptor mRNA
      in the VTA, but elevated amygdala GR, and 6 weeks of cafeteria diet reduced BDNF,
      compared to chow-fed rats. Rats switched to the cafeteria diet ate similar
      amounts as rats maintained on the diet, and switching to cafeteria diet after 15
      weeks reduced amygdala GR expression. Rats switched to chow ate less than rats
      maintained on chow, and switching to chow following 15 weeks of cafeteria diet
      increased hypothalamic CRH mRNA. Therefore, 15 weeks of cafeteria diet produced
      changes in brain regions implicated in reward processes. Switching these rats to
      chow activated the HPA axis, while switching chow-fed rats to the cafeteria diet
      decreased GR expression in the amygdala, a region associated with stress. These
      findings have implications for dieting in humans. 

PMID- 24583193
TI  - Improved PCR-RFLP method for the identification of Escherichia coli
      enterohemolysin (ehxA) subtypes.
AB  - Previously published PCR-RFLP methods failed to detect the six genetically
      different Escherichia coli ehxA subtypes reliably. Here we describe an improved
      PCR-RFLP method that detects all ehxA subtypes. Importantly, ehxA-subtyping may
      contribute to the detection of potentially pathogenic STECs and can expedite
      initial screenings of patient samples and food enrichments. 

PMID- 24583194
TI  - Development of monoclonal antibodies to pre-haptoglobin 2 and their use in an
      enzyme-linked immunosorbent assay (ELISA).
AB  - Haptoglobins (HPs) are alpha 2-globulin proteins that bind free hemoglobin in
      plasma to prevent oxidative damage. HPs are produced as preproteins that are
      proteolytically cleaved in the ER into alpha and beta chains prior to forming
      mature, functional tetramers. Two alleles exist in humans (HP1 and HP2),
      therefore three genotypes are present in the population, i.e., HP1-1, HP2-1, and
      HP2-2. A biochemical role for nascent haptoglobin 2 (pre-haptoglobin 2 or pre
      HP2) as the only known modulator of intestinal permeability has been established.
      In addition, elevated levels of serum pre-HP2 have been detected in multiple
      conditions including celiac disease and type I diabetes, which are believed to
      result in part through dysregulation of the intestinal barrier. In this study, we
      report the development of a monoclonal antibody that is specific for pre-HP2 with
      a binding affinity in the nanomolar range. Additional antibodies with
      specificities for preHP but not mature haptoglobin were also characterized. A
      sandwich enzyme-linked immunosorbent assay (ELISA) was established and validated.
      The ELISA showed high specificity for pre-HP2 even in the presence of excess pre
      HP1 or mature haptoglobins, and has excellent linearity and inter- and intra
      assay reproducibility with a working range from 3.1ng/mL to 200ng/mL. Testing of
      sera from 76 healthy patients revealed a non-Gaussian distribution of pre-HP2
      levels with a mean concentration of 221.2ng/mL (95% CI: 106.5-335.9ng/mL) and a
      median value of 23.9ng/mL. Compared to current approaches, this ELISA offers a
      validated, monoclonal-based method with high sensitivity and specificity for
      measuring pre-HP2 in human serum. 

PMID- 24583196
TI  - Involvement of extrinsic and intrinsic apoptotic pathways together with
      endoplasmic reticulum stress in cell death induced by naphthylchalcones in a
      leukemic cell line: advantages of multi-target action.
AB  - Chalcones, naturally occurring open-chain flavonoids abundant in plants, have
      demonstrated anticancer activity in multiple tumor cells. In a previous work, the
      potential anticancer activity of three naphthylchalcones named R7, R13 and R15
      was shown. In this study, the mechanism of actions of these chalcones was
      originally shown. The chalcones presented concentration and time-dependent
      cytotoxicity. To determine the type of cell death induced by chalcones, we
      assessed a series of assays including measurements of the caspase-8, -9 and -12
      activities, expression of important apoptosis-related genes and proteins, changes
      in the cell calcium concentration and cytochrome c release. The activities of
      caspase-8, -9 and -12 increased after the treatment of L1210 cells with the three
      compounds. Chalcones R7 and R13 induced an increase of pro-apoptotic proteins
      Bax, Bid and Bak (only chalcone R13), as well as a decrease in anti-apoptotic Bcl
      2 expression. These chalcones also induced an increase in Fas and a decrease in
      p21 and p53 expression. Chalcone R15 seems to act by a different mechanism to
      promote cell death, as it did not change the mitochondrion-related proteins, nor
      did it induce the cytochrome c release. All compounds induced an increase in cell
      calcium concentration and an increase in CHOP expression, which together with an
      increase in caspase-12 activity, suggest that chalcones could induce an
      endoplasmic reticulum (ER) stress. Taken together, these results suggest that
      chalcones induce apoptosis by different pathways, being an interesting strategy
      to suggest for cancer therapy. 

PMID- 24583195
TI  - A novel method to measure HLA-DM-susceptibility of peptides bound to MHC class II
      molecules based on peptide binding competition assay and differential IC(50)
      determination.
AB  - HLA-DM (DM) functions as a peptide editor that mediates the exchange of peptides
      loaded onto MHCII molecules by accelerating peptide dissociation and association
      kinetics. The relative DM-susceptibility of peptides bound to MHCII molecules
      correlates with antigen presentation and immunodominance hierarchy, and
      measurement of DM-susceptibility has been a key effort in this field. Current
      assays of DM-susceptibility, based on differential peptide dissociation rates
      measured for individually labeled peptides over a long time base, are difficult
      and cumbersome. Here, we present a novel method to measure DM-susceptibility
      based on peptide binding competition assays performed in the presence and absence
      of DM, reported as a delta-IC(50) (change in 50% inhibition concentration) value.
      We simulated binding competition reactions of peptides with various intrinsic and
      DM-catalyzed kinetic parameters and found that under a wide range of conditions
      the delta-IC(50) value is highly correlated with DM-susceptibility as measured in
      off-rate assay. We confirmed experimentally that DM-susceptibility measured by
      delta-IC(50) is comparable to that measured by traditional off-rate assay for
      peptides with known DM-susceptibility hierarchy. The major advantage of this
      method is that it allows simple, fast and high throughput measurement of DM
      susceptibility for a large set of unlabeled peptides in studies of the mechanism
      of DM action and for identification of CD4+ T cell epitopes.

PMID- 24583197
TI  - Cytotoxicity and gene expression profiling of polyhexamethylene guanidine
      hydrochloride in human alveolar A549 cells.
AB  - In Korea, lung disease of children and pregnant women associated with humidifier
      disinfectant use has become a major concern. A common sterilizer is
      polyhexamethylene guanidine (PHMG), a member of the guanidine family of
      antiseptics. This study was done to elucidate the putative cytotoxic effect of
      PHMG and the PHMG-mediated altered gene expression in human alveolar epithelial
      A549 cells in vitro. Cell viability analyses revealed the potent cytotoxicity of
      PHMG, with cell death evident at as low as 5 MUg/mL. Death was dose- and time
      dependent, and was associated with formation of intracellular reactive oxygen
      species, and apoptosis significantly, at even 2 MUg/mL concentration. The gene
      expression profile in A549 cells following 24 h exposure to 5 MUg/mL of PHMG was
      investigated using DNA microarray analysis. Changes in gene expression relevant
      to the progression of cell death included induction of genes related to
      apoptosis, autophagy, fibrosis, and cell cycle. However, the expressions of genes
      encoding antioxidant and detoxifying enzymes were down-regulated or not affected.
      The altered expression of selected genes was confirmed by quantitative reverse
      transcription-polymerase chain reaction and Western blot analyses. The collective
      data suggest that PHMG confers cellular toxicity through the generation of
      intracellular reactive oxygen species and alteration of gene expression.

PMID- 24583198
TI  - The practical utility of routine postpartum hemoglobin assessment.
AB  - OBJECTIVE: To evaluate a policy of routine versus selective postpartum complete
      blood count (CBC). STUDY DESIGN: Historic case control design with matched
      subjects from 1 year periods bracketing the policy change (n = 800). Our primary
      outcome was postpartum transfusion rate. Univariable and multivariable analyses
      were performed. Total hospital costs were estimated. RESULTS: Eliminating routine
      postpartum CBC testing was associated with decreased transfusion rates (5.5% vs
      1.8%, P = .007) despite similar transfusion risks. CBC utilization decreased from
      59% to 22.2% (P < .0001). No adverse bleeding outcomes occurred. Multivariable
      modeling suggested that the occurrence of postpartum hemorrhage was the best
      clinical predictors of transfusion n risk. Tachycardia, oliguria, and symptoms
      were also effective at identifying transfusion candidates. Elimination of routine
      CBC was independently associated with a reduced risk of transfusion (odds ratio,
      0.30; 95% confidence interval, 0.12-0.72). Annual cost savings were estimated at
      $58,000. CONCLUSION: Targeted CBC testing results in fewer transfusions, lower
      costs and improved quality of patient care.

PMID- 24583199
TI  - Cloud point extraction-HPLC method for the determination and pharmacokinetic
      study of aristolochic acids in rat plasma after oral administration of
      Aristolochiae Fructus.
AB  - Based on cloud-point extraction (CPE), a high performance liquid chromatography
      method (HPLC) was developed and validated for the determination of aristolochic
      acids (AAs) in rat plasma after oral administration of Aristolochiae Fructus
      (AF). Non-ionic surfactant Genapol X-080, an environmentally friendly solvent,
      was used for the micelle-mediated extraction. Various influencing factors on CPE
      process were investigated and optimized. AAs were extracted from rat plasma after
      adding 1ml of 4.5% (v/v) surfactant in the presence of 0.2mol/l HCl and 20mg
      NaCl, and the incubation temperature and time were 50 degrees C and 10min,
      respectively. Base-line separation was obtained for the AAs in rat plasma with
      the optimized chromatography conditions. The detection limits (LOD) reached
      downward 10ng/ml. The intra-day and inter-day precisions were less than 7.8%, the
      accuracies were within +/-5.5%, and the average recovery factors were in the
      range of 94.5-105.4%. In comparison with liquid-liquid extraction, the CPE method
      has a considerable LOD and higher recoveries. The proposed CPE-HPLC method was
      specific, sensitive and reliable, and could be an effective tool for the
      determination of AAs in biological matrixes. With the method the pharmacokinetics
      of AAs were investigated successfully after oral administration of AF by rats. 

PMID- 24583200
TI  - Determination of seven bisphenol analogues in reed and Callitrichaceae by ultra
      performance liquid chromatography-tandem mass spectrometry.
AB  - An analytical procedure was developed to simultaneously determine bisphenol S,
      bisphenol F, bisphenol B, bisphenol A, bisphenol AF, tetrachlorobisphenol A, and
      tetrabromobisphenol A in reed and Callitrichaceae. Homogenized samples were
      extracted with acetonitrile and purified using an ENVITM-Carb cartridge followed
      by an NH2 cartridge. The analytes were separated and quantified by ultra
      performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The
      recoveries at three fortified levels in reed and Callitrichaceae were 57-108% and
      68-106%, respectively, with relative standard deviations of no more than 15%
      (n=6). The method limits of quantification and detection for the seven bisphenol
      analogues were 0.005-0.500MUg/kg and 0.002-0.150MUg/kg, respectively. This method
      was used to analyze the seven compounds in ten reed and Callitrichaceae samples
      collected from Zhejiang, China. 

PMID- 24583201
TI  - Multi-dye residue analysis of triarylmethane, xanthene, phenothiazine and
      phenoxazine dyes in fish tissues by ultra-performance liquid chromatography
      tandem mass spectrometry.
AB  - Beside the possible illegal use of malachite green in aquaculture, other familiar
      dyes could also been applied by fraudulent producers due to their antiseptic and
      antibacterial activity. In this contribution, a new sensitive multi-residue
      method was developed to determine triarylmethane, xanthene, phenothiazine and
      phenoxazine dyes in fish by ultra-performance liquid chromatography-tandem mass
      spectrometry. Samples were extracted with acetonitrile, followed by an oxidation
      step using 2,3-dichloro-5,6-dicyanobenzoquinone. Further clean-up was performed
      by tandem solid phase extraction using weak and strong cation exchange
      cartridges. Extracts were analysed by UPLC-MS(n) operating in the positive
      electrospray ionisation mode (ESI+). The fourteen dyes were separated within only
      12min on a C18 BEH column using 1mM ammonium acetate in water at pH 4.5 and
      acetonitrile as mobile phases at a flowrate of 0.4mLmin(-1). The presented method
      was validated as defined by the European Union and scientific literature. Good
      linearity (R >=0.99 and goodness-of-fit (g) <=10%) was achieved over the tested
      concentration range (0.25-2ngg(-1)). Limit of quantification was 0.25ngg(-1) for
      all dyes, with a signal-to-noise ratio of at least 10/1. This is at least 5 to 10
      times lower than previous published methods. Limits of detection were all
      <0.1ngg(-1). Precision and trueness fell within the criteria requested by the EC
      requirements for this concentration range. Decision limit (CCalpha) and detection
      capability (CCbeta) were all <1 and <0.25ngg(-1), respectively. Due to background
      levels of the xanthene dyes, the two rhodamine dyes could only be determined
      above 0.75ngg(-1). For these dyes, the method can only be used for screening
      purposes. To show the applicability of the method, a monitoring study was
      performed to investigate the occurrence of artificial dyes in wildlife European
      eel in Flemish rivers. 

PMID- 24583202
TI  - In vitro modeling of angiotensin-converting enzyme inhibitor's absorption with
      chromatographic retention data and selected molecular descriptors.
AB  - Set of nine angiotensin-converting enzyme inhibitors (enalapril, quinapril,
      fosinopril, lisinopril, cilazapril, ramipril, benazepril, perindopril and
      moexipril) were studied to evaluate the correlation between their intestinal
      absorption and salting-out thin-layer chromatography hydrophobicity parameters
      (RM(0) or C0) obtained by ascending technique applying four different salts,
      (NH4)2SO4, NH4NO3, NH4Cl and NaCl as mobile phases. The best correlations between
      KOWWIN logP and both hydrophobicity parameters, RM(0) and C0, (R(2)>0.850) were
      observed for NaCl (1.0-3.0M) while the lowest R(2) was obtained for (NH4)2SO4
      (0.649 and 0.427, respectively) due to highest salting-out effect of (NH4)2SO4.
      The effect of selected inorganic salts in the salting-out mobile phases, on the
      solutes solubility and retention was evaluated. The topological polar surface
      area should be selected as independent variable (only this molecular descriptor
      showed low correlation with chromatographic hydrophobicity parameters) for
      multiple linear regression analysis, to obtain reliable correlation between
      angiotensin-converting enzyme inhibitor's intestinal absorption data and salting
      out thin-layer chromatograpic hydrophobicity parameters. These correlations
      provide R(2)=0.823 for RM(0) or R(2)=0.799 for C0 indicating good relationship
      between predicted and literature available intestinal absorption (ranged from 22%
      to 70%) of investigated angiotensin-converting enzyme inhibitors. The proposed in
      vitro model was checked with three in addition experimentally analyzed drugs,
      zofenopril, trandolapril and captoril. The satisfactory absorption prediction was
      obtained for zofenopril and trandolapril, while divergence established for
      captopril resulted from considerably different structure. 

PMID- 24583203
TI  - Novel de novo SPOCK1 mutation in a proband with developmental delay, microcephaly
      and agenesis of corpus callosum.
AB  - Whole exome sequencing made it possible to identify novel de novo mutations in
      genes that might be linked to human syndromes (genotype first analysis). We
      describe a female patient with a novel de novo SPOCK1 variant, which has not been
      previously been associated with a human phenotype. Her features include
      intellectual disability with dyspraxia, dysarthria, partial agenesis of corpus
      callosum, prenatal-onset microcephaly and atrial septal defect with aberrant
      subclavian artery. Previous genetic, cytogenomic and metabolic studies were
      unrevealing. At age 13 years, exome sequencing on the patient and her parents
      revealed a de novo novel missense mutation in SPOCK1 (coding for Testican-1) on
      chromosome 5q31: c.239A>T (p.D80V). This mutation affects a highly evolutionarily
      conserved area of the gene, replacing a polar aspartic acid with hydrophobic
      nonpolar valine, and changing the chemical properties of the protein product,
      likely representing a pathogenic variant. Previous microdeletions of 5q31
      including SPOCK1 have suggested genes on 5q31 as candidates for intellectual
      disability. No mutations or variants in other genes potentially linked to her
      phenotype were identified. Testicans are proteoglycans belonging to the BM
      40/SPARC/osteonectin family of extracellular calcium-binding proteins. Testican-1
      is encoded by the SPOCK1 gene, and mouse models have been shown it to be strongly
      expressed in the brain and to be involved in neurogenesis. We hypothesize that
      because this gene function is critical for neurogenesis, mutations could
      potentially lead to a phenotype with developmental delay and microcephaly. 

PMID- 24583204
TI  - Epigenetic changes associated with inflammation in breast cancer patients treated
      with chemotherapy.
AB  - Inflammation has been associated with fatigue during and after various types of
      breast cancer treatments. We examined whether prior chemotherapy was associated
      with DNA methylation patterns that could explain persisting inflammation and/or
      fatigue in women treated for breast cancer. Prior to breast radiation therapy,
      DNA was extracted from peripheral blood mononuclear cells (PBMCs) of 61 Stage 0
      IIIA breast cancer patients who had received partial mastectomy with or without
      chemotherapy. DNA methylation was assessed at >485,000 CpG sites across the
      genome along with fatigue and plasma inflammatory markers previously associated
      with fatigue. Compared to non-chemotherapy-treated, women who had received
      chemotherapy exhibited significantly decreased methylation at eight CpG sites
      (p<1.03*10(-7)) including four in exon 11 of transmembrane protein 49 (TMEM49),
      which demonstrated the largest decreases in methylation. Lower methylation at
      each identified CpG site was associated with increased plasma soluble tumor
      necrosis factor receptor 2 (sTNFR2) and interleukin (IL)-6 and mediated the
      relationship between chemotherapy and increases in these inflammatory biomarkers
      adjusting for multiple clinical and treatment characteristics. sTNFR2, but not
      CpG methylation status, was correlated with fatigue. Six months after breast
      radiation therapy, DNA methylation, inflammatory biomarkers and fatigue
      assessments were repeated in a subset of subjects (N=39). Reduced methylation in
      4 of the 8 identified CpG sites was still observed in chemotherapy versus non
      chemotherapy-treated patients, albeit with some decay indicating the dynamic and
      potentially reversible nature of the changes. Reduced methylation in these 4 CpG
      sites also continued to correlate with either increased sTNFR2 or IL-6, but not
      fatigue. In conclusion, prior chemotherapy treatment was associated with
      decreased methylation of CpG sites in DNA from PBMCs of breast cancer patients,
      which correlated with increased inflammatory markers prior to and 6months after
      radiation therapy. Persisting epigenetic changes secondary to chemotherapy may be
      one factor that contributes to inflammation and its consequences including cancer
      related fatigue in vulnerable breast cancer patients. 

PMID- 24583205
TI  - Liquid chromatography-tandem mass spectrometry for the analysis of eicosanoids
      and related lipids in human biological matrices: a review.
AB  - Today, there is an increasing number of liquid chromatography tandem-mass
      spectrometric (LC-MS/MS) methods for the analysis of eicosanoids and related
      lipids in biological matrices. An overview of currently applied LC-MS/MS methods
      is given with attention to sample preparation strategies, chromatographic
      separation including ultra high performance liquid chromatography (UHPLC) and
      chiral separation, as well as to mass spectrometric detection using multiple
      reacting monitoring (MRM). Further, the application in recent clinical research
      is reviewed with focus on preanalytical aspects prior to LC-MS/MS analysis as
      well as applications in major diseases of Western civilization including
      respiratory diseases, diabetes, cancer, liver diseases, atherosclerosis, and
      neurovascular diseases.

PMID- 24583206
TI  - Response to Baumgardner et al.

PMID- 24583207
TI  - Comparative in vitro stability and scintigraphic imaging for trafficking and
      tumor targeting of a directly and a novel 99mTc(I)(CO)3 labeled liposome.
AB  - Liposomes radiolabelling with diagnostic radionuclides is an excellent tool for
      studying pharmacokinetics with the view of developing liposome-based drug
      delivery agents. The aim of the present study is to evaluate the in vitro and in
      vivo behavior of a (99m)Tc-labeled liposome by applying either a direct labeling
      strategy via a carboxyl group, LP-COOH, or a surface chelating method via pyridyl
      ethyl cysteine compound (with the intermediate [99mTc(I)(CO)3(H2O)(3)](+)), LP
      PEC. 99mTc-LP-COOH was obtained in high radiolabelling yield and radiochemical
      purity, while 99mTc(I)(CO)3-LP-PEC was initially purified before being in vitro
      and in vivo evaluated. 99mTc-LP-COOH was less stable in the presence of
      competitive for 99mTc ligands than 99mTc(I)(CO)3-LP-PEC. According to DLS
      measurements, the presence of serum as well as the applied radiolabelling
      conditions did not affect the liposomes' size. The different radiolabelling
      methods seemed to exert an influence on the biodistribution pattern of the
      liposomes with the 99mTc(I)(CO)3-LP-PEC showing slow blood clearance, which was
      also confirmed by in vivo scintigraphic imaging. Nevertheless, passive tumor
      targeting was attained at a similar extent no matter which radiolabelling
      technique was followed.

PMID- 24583209
TI  - Pretreatment of corn stover with diluted acetic acid for enhancement of
      acidogenic fermentation.
AB  - A Box-Behnken design of response surface method was used to optimize acetic acid
      catalyzed hydrothermal pretreatment of corn stover, in respect to acid
      concentration (0.05-0.25%), treatment time (5-15 min) and reaction temperature
      (180-210 degrees C). Acidogenic fermentations with different initial pH and
      hydrolyzates were also measured to evaluate the optimal pretreatment conditions
      for maximizing acid production. The results showed that pretreatment with 0.25%
      acetic acid at 191 degrees C for 7.74 min was found to be the most optimal
      condition for pretreatment of corn stover under which the production of acids can
      reach the highest level. Acidogenic fermentation with the hydrolyzate of
      pretreatment at the optimal condition at the initial pH=5 was shown to be butyric
      acid type fermentation, producing 21.84 g acetic acid, 7.246 g propionic acid,
      9.170 butyric acid and 1.035 g isovaleric acid from 100g of corn stover in 900 g
      of water containing 2.25 g acetic acid.

PMID- 24583208
TI  - Freeze-drying of ovalbumin loaded mesoporous silica nanoparticle vaccine
      formulation increases antigen stability under ambient conditions.
AB  - Amino functionalised mesoporous silica nanoparticles (AM-41) have been identified
      as a promising vaccine delivery material. The capacity of AM-41 to stabilise
      vaccine components at ambient temperature (23-27 degrees C) was determined by
      adsorbing the model antigen ovalbumin (OVA) to AM-41 particles (OVA-41). The OVA
      41 was successfully freeze-dried using the excipients 5% trehalose and 1%
      PEG8000. The immunological activity of OVA and the nanoparticle structure were
      maintained following two months storage at ambient temperature. The results of
      immunisation studies in mice with reconstituted OVA-41 demonstrated the induction
      of humoral and cell-meditated immune responses. The capacity of AM-41 particles
      to facilitate ambient storage of vaccine components without the loss of
      immunological potency will underpin the further development of this promising
      vaccine delivery platform. 

PMID- 24583210
TI  - Special biochemical responses to nitrogen deprivation of filamentous oleaginous
      microalgae Tribonema sp.
AB  - Both filamentous microalgae Tribonema and unicellular microalgae Nanochloropsis
      are promising feedstock for biodiesel production. Nitrogen starvation increased
      lipid content in Nannochloropsis but decreased that in Tribonema. In this study,
      biochemical responses of Tribonema under different levels of nitrogen (0N, 0.05N,
      0.1N and 1N-BG11) were investigated. 1N-BG11 was sufficient during 15-day
      cultivation, while the other levels were nitrogen limited. Cell growth was
      interrupted with 0N-BG11, but no differences in biomass among 0.05N, 0.1N and 1N
      BG11. Both protein and lipid contents (% of dry weight) declined gradually
      inversely to the increment in carbohydrate contents under the decreasement of
      nitrogen levels. Both assays and TEM results showed that the cytoplasm in
      Tribonema contained no starch. Compared to nitrogen-replete condition, the TAG
      content (% of dry weight) decreased obviously under nitrogen starvation.
      Different levels of nitrogen did not cause fundamental shifts in fatty acid
      profiles in Tribonema. 

PMID- 24583211
TI  - The influence of zeolite (clinoptilolite) on the performance of a hybrid membrane
      bioreactor.
AB  - This work aims to investigate the effect of clinoptilolite on the performance of
      membrane bioreactor (MBR). The control membrane bioreactor without clinoptilolite
      (CMBR) and the hybrid membrane bioreactor with clinoptilolite (HMBR), in two
      parallel simultaneous MBRs within long and short term filtration experiments,
      were studied. Sludge properties, transmembrane pressure (TMP) rise as an index
      for membrane fouling and nutrient removal from synthetic wastewater in the CMBR
      and HMBR were compared. In HMBR, sludge properties improvement such as 22.5% rise
      in MLSS, 7% more accumulation of large particles, reduction of soluble microbial
      products (SMP) to half of this value in CMBR, no increase in sludge volume index
      (SVI) and 66% TMP reduced. The results of short term filtration showed that the
      trend of TMP increase in terms of flux will be slower in HMBR. Improvement of
      biological wastewater treatment quality and ease of membrane operation are
      concluded from this study.

PMID- 24583212
TI  - Improved dechlorination and mineralization of 4-chlorophenol in a sequential
      biocathode-bioanode bioelectrochemical system with mixed photosynthetic bacteria.
AB  - A new approach that improved the dechlorination and mineralization of 4
      chlorophenol (4-CP) was demonstrated in a sequential biocathode-bioanode
      bioelectrochemical system (BES) with mixed photosynthetic bacteria (PSB). The
      biocathode with additional PSB inoculation showed higher 4-CP dechlorination
      efficiency (DE) and maximum current (81.8 +/- 2.9%, 0.021 +/- 0.002A) than that
      at abiotic cathode (45.3 +/- 3.7%, 0.011 +/- 0.002A) (P<0.005). Light response in
      biocathode BES with or without PSB ascertained the important role of PSB played
      in the dechlorination and current generation. Dechlorination and mineralization
      of 4-CP was achieved in the sequential biocathode-bioanode BES, which could be
      further enhanced with PSB inoculation in both cathode chamber and anode chamber.
      4-CP DE in the cathode chamber was improved from 55.0 +/- 2.0% to 78.8 +/- 4.9%,
      and the phenol degradation in the anode chamber was improved from 65.3 +/- 2.1%
      to 71.3 +/- 1.4%. This study directed a new way for improving dechlorination at
      biocathode and product degradation at bioanode with PSB inoculation in BES.

PMID- 24583213
TI  - A novel continuous flow biosynthesis of caffeic acid phenethyl ester from alkyl
      caffeate and phenethanol in a packed bed microreactor.
AB  - Caffeic acid phenethyl ester (CAPE) is a rare natural ingredient with several
      biological activity, but the industrial production of CAPE using lipase-catalyzed
      esterification of caffeic acid (CA) and 2-phenylethanol (PE) in ionic liquids is
      hindered by low substrate concentrations and a long reaction time. To establish a
      high-efficiency bioprocess for obtaining CAPE, a novel continuous flow
      biosynthesis of CAPE from alkyl caffeate and PE in [Bmim][Tf2N] using a packed
      bed microreactor was successfully carried out. Among the tested alkyl caffeates
      and lipases, methyl caffeate and Novozym 435, respectively, were selected as the
      suitable substrate and biocatalyst. Under the optimum conditions selected using
      response surface methodology, a 93.21% CAPE yield was achieved in 2.5h using a
      packed bed microreactor, compared to 24h using a batch reactor. The reuse of
      Novozym 435 for 20 cycles and continuous reaction for 9 days did not result in
      any decrease in activity.

PMID- 24583214
TI  - Fungal hydrolysis in submerged fermentation for food waste treatment and
      fermentation feedstock preparation.
AB  - Potential of fungal hydrolysis in submerged fermentation by Aspergillus awamori
      and Aspergillus oryzae as a food waste treatment process and for preparation of
      fermentation feedstock has been investigated. By fungal hydrolysis, 80-90% of the
      initial amount of waste was reduced and degraded within 36-48 h into glucose,
      free amino nitrogen (FAN) and phosphate. Experiments revealed that 80-90% of
      starch can be converted into glucose and highest concentration of FAN obtained,
      when solid mashes of A. awamori and A. oryzae are successively added to
      fermentations at an interval of 24h. A maximal solid-to-liquid ratio of 43.2%
      (w/v) of food waste has been tested without a negative impact on releases of
      glucose, FAN and phosphate, and final concentrations of 143 g L(-1), 1.8 g L(-1)
      and 1.6 g L(-1) were obtained in the hydrolysate, respectively. Additionally,
      fungal hydrolysis as an alternative to conventional treatments for utilization of
      food waste is discussed.

PMID- 24583215
TI  - Two-stage thermal conversion of inedible lipid feedstocks to renewable chemicals
      and fuels.
AB  - The aim of this work was to study the conversion of inedible, low cost lipid
      feedstocks to renewable hydrocarbons using a two stage thermal hydrolysis
      pyrolysis method. Beef tallow, yellow grease, brown grease and cold pressed
      camelina oil were first hydrolyzed and the fatty acids produced were recovered
      and pyrolyzed in batch reactors. The pyrolysis products were identified and
      quantified using gas chromatography and mass spectrometry. The pyrolysis product
      yields were similar for all the feedstock used with the organic liquid fraction
      (OLF) accounting for 76-80% of the product. The OLF consisted predominantly of n
      alkanes. Approximately 30% OLF constituted a gasoline-equivalent fraction and 50%
      a diesel fraction. Other fuel property test showed that the OLF met the
      specifications set out by the Canadian general standards board. This research
      demonstrated a novel two-stage thermal hydrolysis-pyrolysis conversion method for
      producing OLF from inedible and low-value lipids. 

PMID- 24583216
TI  - The headspace of microaerobic reactors: sulphide-oxidising population and the
      impact of cleaning on the efficiency of biogas desulphurisation.
AB  - O2-limiting/microaerobic conditions were applied in order to control the H2S
      content of biogas. The S(0)-rich deposits found all over the headspace of two
      pilot reactors (R1 and R2) as a result of operating under such conditions for 7
      and 15 months (respectively) were sampled and removed. After restarting micro
      oxygenation, H2S-free biogas was rapidly obtained, and the O2 demand of R2
      decreased. This highlighted the need for a cleaning interval of less than 14
      months in order to minimise the micro-oxygenation cost. The H2S removed from R2
      after approximately 1 month was recovered from its headspace as S(0), thus
      indicating that the biogas desulphurisation did not take place at the liquid
      interface. Denaturing gradient gel electrophoresis indicated that the
      composition, species richness and size of the sulphide-oxidising bacteria
      population depended on the location, and, more specifically, moisture
      availability, and indicated increasing species richness over time. Additionally,
      a possible succession was estimated.

PMID- 24583217
TI  - An investigation on the catalytic capacity of dolomite in transesterification and
      the calculation of kinetic parameters.
AB  - The catalytic capacity of dolomite in transesterification was investigated and
      the kinetic parameters were calculated. The activated dolomites as
      transesterification catalyst were characterized by X-ray diffraction, nitrogen
      adsorption and desorption and Hammett indicator method, where the original
      dolomite was analyzed by thermogravimetric and X-ray fluorescence in advance. Its
      potential catalytic capacity was validated from aspects of the activated
      temperature and the reused property, where the reliability of the experimental
      system was also examined. Then, influences of the catalyst added amount, the mole
      ratio of methanol to oil, the transesterification temperature and the
      transesterification time on the catalytic capacity were investigated. Finally,
      kinetic parameters of the transesterification catalyzed by the activated dolomite
      were calculated. 

PMID- 24583218
TI  - Production of bio-hydrogenated diesel by catalytic hydrotreating of palm oil over
      NiMoS2/gamma-Al2O3 catalyst.
AB  - Catalytic hydrotreating of palm oil (refined palm olein type) to produce bio
      hydrogenated diesel (BHD) was carried out in a continuous-flow fixed-bed reactor
      over NiMoS2/gamma-Al2O3 catalyst. Effects of dominant hydrotreating parameters:
      temperature: 270-420 degrees C; H2 pressure: 15-80 bar; LHSV: 0.25-5.0 h(-1); and
      H2/oil ratio: 250-2000 N(cm(3)/cm(3)) on the conversion, product yield, and a
      contribution of hydrodeoxygenation (HDO) and decarbonylation/decarboxylation
      (DCO/DCO2) were investigated to find the optimal hydrotreating conditions. All
      calculations including product yield and the contribution of HDO and DCO/DCO2
      were extremely estimated based on mole balance corresponding to the fatty acid
      composition in feed to fully understand deoxygenation behaviors at different
      conditions. These analyses demonstrated that HDO, DCO, and DCO2 reactions
      competitively occurred at each condition, and had different optimal and limiting
      conditions. The differences in the hydrotreating reactions, liquid product
      compositions, and gas product composition were also discussed.

PMID- 24583219
TI  - Two-step thermal conversion of oleaginous microalgae into renewable hydrocarbons.
AB  - The aim of this study was to evaluate the conversion of microalgal biomass to
      renewable chemicals and fuels through a two-step reaction and separation process.
      High density Chlorella protothecoides culture with 40% lipid accumulation (dwb)
      was produced in 10 L bioreactors and hydrolyzed in batch stainless steel reactors
      under subcritical conditions. After hydrolysis, fatty acids free of sulfur and
      low in nitrogen and salts, were recovered by hexane extraction. The fatty acids
      were pyrolyzed at 410 degrees C for 2h under N2 yielding n-alkanes, alpha-olefins
      and internal olefins and low molecular weight fatty acids. This study
      demonstrated the direct conversion of microalgal biomass into valuable platform
      chemicals and fuels compatible with the existing industrial hydrocarbon
      infrastructure.

PMID- 24583220
TI  - Hollow glass microspheres for temperature and irradiance control in
      photobioreactors.
AB  - The addition of hollow glass microspheres (HGM) to polymers to change thermal
      insulation and mechanical properties is widely used. In this study HGM were
      tested as a new construction material for photobioreactors to control irradiance
      and broth temperature in microalgae cultivation. The heat isolation properties of
      HGMs of three different densities were tested in a polymer matrix. The
      transmittance (5-50%) and the thermal conductivity (182.05-190.73 W/mK) of the
      HGM composite material were analyzed. The results were tested in a model to
      predict the broth temperature and the growth rate as a function of temperature
      and irradiance. The addition of 1.3 and 0.6 vol.% of HGM lead to an increase in
      the growth rate of up to 37% and a reduction in the broth temperature up to 9
      degrees C. The mechanical resistance of the composites tested is similar to the
      polymer matrix.

PMID- 24583221
TI  - Dimethyl carbonate-mediated lipid extraction and lipase-catalyzed in situ
      transesterification for simultaneous preparation of fatty acid methyl esters and
      glycerol carbonate from Chlorella sp. KR-1 biomass.
AB  - Fatty acid methyl esters (FAMEs) and glycerol carbonate were simultaneously
      prepared from Chlorella sp. KR-1 containing 40.9% (w/w) lipid using a reactive
      extraction method with dimethyl carbonate (DMC). DMC was used as lipid extraction
      agent, acyl acceptor for transesterification of the extracted triglycerides,
      substrate for glycerol carbonate synthesis from glycerol, and reaction medium for
      the solvent-free reaction system. For 1g of biomass, 367.31 mg of FAMEs and 16.73
      mg of glycerol carbonate were obtained under the optimized conditions: DMC to
      biomass ratio of 10:1 (v/w), water content of 0.5% (v/v), and Novozyme 435 to
      biomass ratio of 20% (w/w) at 70 degrees C for 24h. The amount of residual
      glycerol was only in the range of 1-2.5mg. Compared to conventional method, the
      cost of FAME production with the proposed technique could be reduced by combining
      lipid extraction with transesterification and omitting the extraction solvent
      recovery process.

PMID- 24583222
TI  - Anaerobic digestion of horse dung mixed with different bedding materials in an
      upflow solid-state (UASS) reactor at mesophilic conditions.
AB  - Aim of this study was to investigate the use of upflow anaerobic solid-state
      (UASS) digestion for treating horse manure. Biochemical methane potential (BMP)
      tests conducted for varying mixtures of dung (hay and silage feed) and bedding
      material (wheat straw, flax, hemp, wood chips) showed that straw mixed with hay
      horse dung has the highest potential of [Formula: see text] . Continuous
      mesophilic digestion was conducted for 238 days using a single-stage UASS reactor
      (27 L) and a two-stage UASS system with an anaerobic filter (AF, 21 L).
      Increasing the organic loading rate (OLR) from 2.5 to 4.5 g vs L(-1)d(-1)
      enhanced the methane rate of the single-stage reactor from 0.262 to 0.391 LL(
      1)d(-1) while the methane yield declined from 104.8 to 86.9 L kg vs(-1). The two
      stage system showed similar yields. Thus, for solid-state digestion of horse
      manure a single-stage UASS reactor appears sufficient.

PMID- 24583223
TI  - Seeing Jesus in toast: neural and behavioral correlates of face pareidolia.
AB  - Face pareidolia is the illusory perception of non-existent faces. The present
      study, for the first time, contrasted behavioral and neural responses of face
      pareidolia with those of letter pareidolia to explore face-specific behavioral
      and neural responses during illusory face processing. Participants were shown
      pure-noise images but were led to believe that 50% of them contained either faces
      or letters; they reported seeing faces or letters illusorily 34% and 38% of the
      time, respectively. The right fusiform face area (rFFA) showed a specific
      response when participants "saw" faces as opposed to letters in the pure-noise
      images. Behavioral responses during face pareidolia produced a classification
      image (CI) that resembled a face, whereas those during letter pareidolia produced
      a CI that was letter-like. Further, the extent to which such behavioral CIs
      resembled faces was directly related to the level of face-specific activations in
      the rFFA. This finding suggests that the rFFA plays a specific role not only in
      processing of real faces but also in illusory face perception, perhaps serving to
      facilitate the interaction between bottom-up information from the primary visual
      cortex and top-down signals from the prefrontal cortex (PFC). Whole brain
      analyses revealed a network specialized in face pareidolia, including both the
      frontal and occipitotemporal regions. Our findings suggest that human face
      processing has a strong top-down component whereby sensory input with even the
      slightest suggestion of a face can result in the interpretation of a face. 

PMID- 24583224
TI  - Age- and gender-specific reference values for urine albumin/creatinine ratio in
      children of southwest China.
AB  - BACKGROUND: The reference value for the urine albumin/creatinine ratio (ACR)
      varies between races and has not been previously validated in children. We
      assessed the ACR reference values and the factors that affect them in a
      population of healthy Chinese children. METHODS: A total of 1986 healthy children
      (1078 males, 908 females) aged 6-19 y were enrolled. The 95th percentile of ACR
      was used as the normal upper limit. The associations between ACR and gender, age,
      body mass index (BMI), systolic blood pressure (SBP), preterm birth, intake of
      fruits, smoking, and geographical area were examined. RESULTS: The normal upper
      limit of ACR was 14.7 mg/g for male children and 19.8 mg/g for female children.
      The ACR value for girls was significantly higher than that for boys (P<0.001).
      ACR was inversely correlated with age (P<0.001) and positively correlated with
      BMI, SBP, and smoking (all P<0.01). CONCLUSIONS: The ACR reference value for
      healthy children in southwest China is approximately the same as the value for
      adults, but lower than that for the Western population. Age, SBP, BMI, and
      smoking in children influence ACR.

PMID- 24583225
TI  - Investigation of circulating lncRNAs in B-cell neoplasms.
AB  - Long non-coding RNAs (lncRNA) which are longer than 200 base pairs in length,
      play an important role in cellular machinery. Chronic lymphocytic leukemia (CLL)
      and multiple myeloma (MM) are neoplasms of B-cells. In our study we aimed to
      investigate circulating lncRNA levels of CLL and MM patients. For this purpose we
      selected 5 candidate lncRNAs (TUG1, LincRNA-p21, MALAT1, HOTAIR, and GAS5) where
      the first two are regulated by p53. Analyses were performed by real-time PCR
      using cDNA synthesized from plasma RNAs. In both disease groups differential
      levels of plasma lncRNAs were observed. LincRNA-p21 was the only molecule
      displaying significant changes in the CLL group while all remaining lncRNAs
      showed significant differences in the MM group. In the MM group only TUG1 showed
      higher levels than the healthy volunteers. In conclusion, the expression levels
      of the candidate lncRNA molecules display a general trend for tissue- and disease
      specific expression which can provide important potential biomarkers specific to
      the particular disease type. However, further studies are necessary to elucidate
      their involvement in disease development and progression. 

PMID- 24583226
TI  - TATI as a biomarker.
AB  - Tumor-associated trypsin inhibitor (TATI) [also called serine peptidase inhibitor
      Kazal type1, SPINK1 and, in the pancreas, pancreatic secretory trypsin inhibitor
      (PSTI)] inhibits trypsin and other serine proteinases and is expressed in several
      tissues. In addition to being a protease inhibitor, it also acts as an acute
      phase reactant and a growth factor. Furthermore, it may modulate apoptosis, play
      a role in reproduction, and be essential for normal tissue differentiation and
      repair. Serum TATI is elevated in many cancers and can thus be used as a
      diagnostic marker. Over-expression of TATI predicts an unfavorable outcome in
      several cancers and serum TATI can be used to identify patients at increased risk
      of aggressive disease. Serum TATI also increases in acute pancreatitis. Some TATI
      mutations predict susceptibility to recurrent or chronic pancreatitis. Recent
      developments in assay technologies may help in identifying mutation carriers
      conveniently without DNA testing. As TATI acts as a growth factor in some
      cancers, it has also been suggested as a therapeutic target. Taken together,
      assessment of TATI has several potentially important clinical applications. 

PMID- 24583227
TI  - Pathogenicity of conidia-based preparations of entomopathogenic fungi against the
      greenhouse pest aphids Myzus persicae, Aphis gossypii, and Aulacorthum solani
      (Hemiptera: Aphididae).
AB  - Seeking new isolates of entomopathogenic fungi with greater virulence against
      greenhouse aphid pests than those currently registered in North America for
      control of these insects, single-dose screening assays of 44 selected fungal
      isolates and 4 commercially available strains were conducted against first-instar
      nymphs of Myzus persicae and Aphis gossypii. The assays identified a number of
      Beauveria and Metarhizium isolates with virulence equal to or greater than that
      of the commercial strains against the nymphal aphids, but none exhibited
      exceptionally high virulence. Virulence of Isaria isolates was unexpectedly low
      (<31% mortality at doses>1000conidia/mm(2)). In dose-response assays, Beauveria
      ARSEF 5493 proved most virulent against M. persicae and A. gossypii; however,
      LC50s of this isolate did not differ significantly from those of B. bassiana
      commercial strain JW-1. Dose-response assays were also conducted with Aulacorthum
      solani, the first reported evaluations of Beauveria and Metarhizium against this
      pest. The novel isolate Metarhizium 5471 showed virulence?that of Beauveria 5493
      in terms of LC25 and LC50, but 5493 produced a steeper dose response (slope).
      Additional tests showed that adult aphids are more susceptible than nymphs to
      fungal infection but confirmed that infection has a limited pre-mortem effect on
      aphid reproduction. Effects of assay techniques and the potential of fungal
      pathogens as aphid-control agents are discussed. 

PMID- 24583228
TI  - Foodborne anisakiasis and allergy.
AB  - Human anisakiasis, a disease caused by Anisakis spp. (Nematoda), is often
      associated with clinical signs that are similar to those associated with
      bacterial or viral gastroenteritis. With the globalisation of the seafood
      industry, the risk of humans acquiring anisakiasis in developed countries appears
      to be underestimated. The importance of this disease is not only in its initial
      manifestation, which can often become chronic if the immune response does not
      eliminate the worm, but, importantly, in its subsequent sensitisation of the
      human patient. This sensitisation to Anisakis-derived allergens can put the
      patient at risk of an allergic exacerbation upon secondary exposure. This article
      reviews some aspects of this food-borne disease and explains its link to chronic,
      allergic conditions in humans.

PMID- 24583229
TI  - Crystal structure of the carbapenem intrinsic resistance protein CarG.
AB  - In the Gram-negative enterobacterium Erwinia (Pectobacterium) and Serratia sp.
      ATCC 39006, intrinsic resistance to the carbapenem antibiotic 1-carbapen-2-em-3
      carboxylic acid is mediated by the CarF and CarG proteins, by an unknown
      mechanism. Here, we report a high-resolution crystal structure for the Serratia
      sp. ATCC 39006 carbapenem resistance protein CarG. This structure of CarG is the
      first in the carbapenem intrinsic resistance (CIR) family of resistance proteins
      from carbapenem-producing bacteria. The crystal structure shows the protein to
      form a homodimer, in agreement with results from analytical gel filtration. The
      structure of CarG does not show homology with any known antibiotic resistance
      proteins nor does it belong to any well-characterised protein structural family.
      However, it is a close structural homologue of the bacterial inhibitor of
      invertebrate lysozyme, PliI-Ah, with some interesting structural variations,
      including the absence of the catalytic site responsible for lysozyme inhibition.
      Both proteins show a unique beta-sandwich fold with short terminal alpha-helices.
      The core of the protein is formed by stacked anti-parallel sheets that are
      individually very similar in the two proteins but differ in their packing
      interface, causing the splaying of the two sheets in CarG. Furthermore, a
      conserved cation binding site identified in CarG is absent from the homologue. 

PMID- 24583230
TI  - Changes in antiviral susceptibility to entry inhibitors and endocytic uptake of
      dengue-2 virus serially passaged in Vero or C6/36 cells.
AB  - The aim of the present study was to analyze the influence of virus origin,
      mammalian or mosquito cell-derived, on antiviral susceptibility of DENV-2 to
      entry inhibitors and the association of this effect with any alteration in the
      mode of entry into the cell. To this end, ten serial passages of DENV-2 were
      performed in mosquito C6/36 cells or monkey Vero cells and the antiviral
      susceptibility of each virus passage to sulfated polysaccharides (SPs), like
      heparin and carrageenans, was evaluated by a virus plaque reduction assay. After
      serial passaging in Vero cells, DENV-2 became increasingly resistant to SP
      inhibition whereas the antiviral susceptibility was not altered in virus
      propagated in C6/36 cells. The change in antiviral susceptibility was associated
      to a differential mode of entry into the host cell. The route of endocytic entry
      for productive Vero cell infection was altered from a non-classical clathrin
      independent pathway for C6/36-grown virus to a clathrin-mediated endocytosis when
      the virus was serially propagated in Vero cells. Our results show the impact of
      the cellular system used for successive propagation of DENV on the initial
      interaction between the host cell and the virion in the next round of infection
      and the relevant consequences it might have during the in vitro evaluation of
      entry inhibitors. 

PMID- 24583231
TI  - The conserved sumoylation consensus site in TRIM5alpha modulates its immune
      activation functions.
AB  - TRIM5alpha is a type I interferon-stimulated anti-retroviral restriction factor
      expressed in most primates and homologous proteins are expressed in other
      mammals. Through its C-terminal PRYSPRY (B30.2) domain, TRIM5alpha binds to
      incoming and intact post-fusion retroviral cores in the cytoplasm. Following this
      direct interaction, the retroviral capsid core is destabilized and progression of
      the virus life cycle is interrupted. Specific recognition of its viral target by
      TRIM5alpha also triggers the induction of an antiviral state involving the
      activation of transcription factors NF-kappaB- and AP-1. In addition to PRYSPRY,
      several other TRIM5alpha domains are important for anti-retroviral function,
      including a RING zinc-binding motif. This domain has "E3" ubiquitin ligase
      activity and is involved in both the direct inhibition of incoming retroviruses
      and innate immune activation. A highly conserved sumoylation consensus site is
      present between the RING motif and the N-terminal extremity of TRIM5alpha. No
      clear role in restriction has been mapped to this sumoylation site, and no
      sumoylated forms of TRIM5alpha have been observed. Here we confirm that mutating
      the putatively sumoylated lysine (K10) of the Rhesus macaque TRIM5alpha
      (TRIM5alphaRh) to an arginine has only a small effect on restriction. However, we
      show that the mutation significantly decreases the TRIM5alpha-induced generation
      of free K63-linked ubiquitin chains, an intermediate in the activation of innate
      immunity pathways. Accordingly, K10R decreases TRIM5alpha-mediated activation of
      both NF-kappaB and AP-1. Concomitantly, we find that K10R causes a large increase
      in the levels of ubiquitylated TRIM5alpha. Finally, treatment with the nuclear
      export inhibitor leptomycin B shows that K10R enhances the nuclear localization
      of TRIM5alphaRh, while at the same time reducing its level of association with
      nuclear SUMO bodies. In conclusion, the TRIM5alpha sumoylation site appears to
      modulate the E3 ubiquitin ligase activities of the adjacent RING domain,
      promoting K63-linked ubiquitin chains at the expense of auto-ubiquitylation which
      is probably K48-linked. Consistently, we find this sumoylation site to be
      important for innate immune activation by TRIM5alpha. In addition, lysine 10
      regulates TRIM5alpha nuclear shuttling and nuclear localization, which may also
      be related to its role in innate immunity activation. 

PMID- 24583232
TI  - Modulation of immune function by glutamatergic neurons in the cerebellar
      interposed nucleus via hypothalamic and sympathetic pathways.
AB  - Our recent work has shown that the cerebellar interposed nucleus (IN) contains
      glutamatergic neurons that send axons directly to the hypothalamus. In the
      present study, we aimed to demonstrate modulation of cellular and humoral
      immunity by glutamatergic neurons in the cerebellar IN by means of gene
      interventions of glutaminase (GLS), an enzyme for glutamate synthesis, and to
      reveal pathways transmitting the immunomodulation. Injection of GLS-shRNA
      lentiviral vector into bilateral cerebellar IN downregulated GLS expression in
      the IN. The silencing of GLS gene in the cerebellar IN decreased interleukin (IL)
      2 and interferon (IFN)-gamma production, B-cell number, and IgM antibody level in
      response to antigen bovine serum albumin (BSA). On the contrary, injection of GLS
      lentiviral vector into bilateral cerebellar IN upregulated GLS expression in the
      IN. The GLS gene overexpression in the IN caused opposite immune effects to the
      GLS gene knockdown. Simultaneously, the GLS gene silencing in the cerebellar IN
      reduced and the GLS overexpression elevated glutamate content in the
      hypothalamus, but they both did not affect glycine and GABA contents in the
      hypothalamus. In addition, the immune changes caused by the GLS gene
      interventions in the IN were accompanied by alteration in norepinephrine content
      in the spleen and mesenteric lymph nodes but not by changes in adrenocortical and
      thyroid hormone levels in serum. These findings indicate that glutamatergic
      neurons in the cerebellar IN regulate cellular and humoral immune responses and
      suggest that such immunoregulation may be conveyed by cerebellar IN-hypothalamic
      glutamatergic projections and sympathetic nerves that innervate lymphoid tissues.

PMID- 24583233
TI  - Viewpoints on vessels and vanishing bones in Gorham-Stout disease.
AB  - Gorham-Stout disease (GSD) is a rare disorder characterized by the proliferation
      of endothelial-lined vessels in bone and the progressive destruction of bone.
      Although Jackson described the first case of GSD in 1838, the clinical and
      histological features of GSD were not defined until Gorham and Stout published
      their report on massive osteolysis in 1955. In the years since Gorham and Stout's
      groundbreaking publication, more than 300 cases of GSD have been described in the
      literature. These reports have revealed that the progressive resorption of bone
      in GSD causes severe physical deformities, disabilities, and life-threatening
      complications. Unfortunately, the underlying cause of GSD remains unknown and, as
      a result, the therapeutic options for individuals with GSD are limited. Here we
      review the latest advances in GSD research and present strategies to address
      basic and clinical research questions related to GSD. 

PMID- 24583234
TI  - Structural diversity of a collagen-binding matrix protein from the byssus of blue
      mussels upon refolding.
AB  - Blue mussels firmly adhere to a variety of different substrates by the byssus, an
      extracorporal structure consisting of several protein threads. These threads are
      mainly composed of fibrillar collagens called preCols which are embedded in a
      proteinaceous matrix. One of the two so far identified matrix proteins is the
      Proximal Thread Matrix Protein 1 (PTMP1). PTMP1 comprises two von Willebrand
      factor type A-like domains (A1 and A2) in a special arrangement. Here, we
      describe the refolding of recombinant PTMP1 from inclusion bodies. PTMP1 refolded
      into two distinct monomeric isoforms. Both isomers exhibited alternative
      intramolecular disulfide bonds. One of these isomers is thermodynamically favored
      and presumably represents the native form of PTMP1, while the other isoform is
      kinetically favored but is likely non-native. Oligomerization during refolding
      was influenced by, but not strictly dependent on disulfide formation. The
      conformational stability of PTMP1 indicates an influence of intramolecular
      disulfides on the native state, but not on unfolding intermediates. Monomeric
      PTMP1 exhibited a high thermal stability, dependent on the pH of the surrounding
      environment. Especially under acidic conditions the disulfide bonds were
      critically involved in thermal stability. 

PMID- 24583235
TI  - Structural dynamics of V3 loop in a trimeric ambiance, a molecular dynamics study
      on gp120-CD4 trimeric mimic.
AB  - Entry of HIV virus into the host cell is initiated by the interaction of its
      surface exposed gp120 protein with the cell surface CD4 receptor and a co
      receptor that can be either CCR5 or CXCR4. The third variable region (V3 loop) of
      gp120 has an important role in co-receptor selection by gp120 and forms an
      epitope for neutralizing antibodies. In this work the dynamical behavior of the
      V3 loop in a trimeric environment has been investigated by generating an
      atomistic trimer model of gp120-CD4 complex and has been compared with the result
      of a monomeric gp120-CD4 complex. The main results coming from this work are that
      the three V3 loops belonging to the three subunits of the trimer display a
      different dynamical behavior in terms of its flexibility, spatial orientation,
      motion along the principal modes, conformations, solvent exposure and
      electrostatic potential distribution. We propose that the ability of the V3 loop
      to present, in the trimeric environment, simultaneous multiple alternative
      conformations that increase its capability of co-receptor recognition, is at
      least in part due to the effect of electrostatic potential generated by two
      subunits over the third one. 

PMID- 24583236
TI  - Extending shikimate pathway for the production of muconic acid and its precursor
      salicylic acid in Escherichia coli.
AB  - cis,cis-Muconic acid (MA) and salicylic acid (SA) are naturally-occurring organic
      acids having great commercial value. MA is a potential platform chemical for the
      manufacture of several widely-used consumer plastics; while SA is mainly used for
      producing pharmaceuticals (for example, aspirin and lamivudine) and skincare and
      haircare products. At present, MA and SA are commercially produced by organic
      chemical synthesis using petro-derived aromatic chemicals, such as benzene, as
      starting materials, which is not environmentally friendly. Here, we report a
      novel approach for efficient microbial production of MA via extending shikimate
      pathway by introducing the hybrid of an SA biosynthetic pathway with its partial
      degradation pathway. First, we engineered a well-developed phenylalanine
      producing Escherichia coli strain into an SA overproducer by introducing
      isochorismate synthase and isochorismate pyruvate lyase. The engineered strain is
      able to produce 1.2g/L of SA from simple carbon sources, which is the highest
      titer reported so far. Further, the partial SA degradation pathway involving
      salicylate 1-monoxygenase and catechol 1,2-dioxygenase is established to achieve
      the conversion of SA to MA. Finally, a de novo MA biosynthetic pathway is
      assembled by integrating the established SA biosynthesis and degradation modules.
      Modular optimization enables the production of up to 1.5g/L MA within 48h in
      shake flasks. This study not only establishes an efficient microbial platform for
      the production of SA and MA, but also demonstrates a generalizable pathway design
      strategy for the de novo biosynthesis of valuable degradation metabolites. 

PMID- 24583238
TI  - Finite element analysis of stress and wear characterization in total ankle
      replacements.
AB  - Total Ankle Arthroplasty is performed in order to reduce the pain and loss of
      ambulation in patients with various forms of arthritis and trauma. Although
      replacement devices fail by a number of mechanisms, wear in the polyethylene
      liner constitutes one of the dominating failure modes. This leads to instability
      and loosening of the implant. Mechanisms that contribute to wear in the liners
      are high contact and subsurface stresses that break down the material over time.
      Therefore, it is important to understand the gait that generates these stresses.
      Methods to characterize and decrease wear in Ohio Total Ankle Replacements (TARs)
      have been performed in this research. This research utilizes finite element
      analysis of Wright State University (WSU) patented TAR models. From the Finite
      element analysis (FEA) results, mathematical models of contact conditions and
      wear mechanics were developed. The maximum wear rate values obtained in the study
      (at 25.598MPa, 3.74mm(3)/year) and maximum surface Mises stress obtained with new
      optimization model (11.52MPa) seem to be comparable with the maximum wear values
      obtained in other similar studies. These models were used to determine the best
      methods for wear characterization and reduction. Furthermore, optimization models
      were developed based on geometry of the implants. These equations optimize
      geometry, thus congruency and anatomical simulations for total ankle implants. 

PMID- 24583237
TI  - Enzymatic and structural characterization of an archaeal thiamin phosphate
      synthase.
AB  - Studies on thiamin biosynthesis have so far been achieved in eubacteria, yeast
      and plants, in which the thiamin structure is formed as thiamin phosphate from a
      thiazole and a pyrimidine moiety. This condensation reaction is catalyzed by
      thiamin phosphate synthase, which is encoded by the thiE gene or its orthologs.
      On the other hand, most archaea do not seem to have the thiE gene, but instead
      their thiD gene, coding for a 2-methyl-4-amino-5-hydroxymethylpyrimidine (HMP)
      kinase/HMP phosphate kinase, possesses an additional C-terminal domain designated
      thiN. These two proteins, ThiE and ThiN, do not share sequence similarity. In
      this study, using recombinant protein from the hyperthermophile archaea
      Pyrobaculum calidifontis, we demonstrated that the ThiN protein is an analog of
      the ThiE protein, catalyzing the formation of thiamin phosphate with the release
      of inorganic pyrophosphate from HMP pyrophosphate and 4-methyl-5-beta
      hydroxyethylthiazole phosphate (HET-P). In addition, we found that the ThiN
      protein can liberate an inorganic pyrophosphate from HMP pyrophosphate in the
      absence of HET-P. A structure model of the enzyme-product complex of P.
      calidifontis ThiN domain was proposed on the basis of the known three-dimensional
      structure of the ortholog of Pyrococcus furiosus. The significance of Arg320 and
      His341 residues for thiN-coded thiamin phosphate synthase activity was confirmed
      by site-directed mutagenesis. This is the first report of the experimental
      analysis of an archaeal thiamin synthesis enzyme. 

PMID- 24583239
TI  - Pharmacokinetic comparison of seven major bio-active components in normal and
      blood deficiency rats after oral administration of Danggui Buxue decoction by
      UPLC-TQ/MS.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Blood deficiency is commonly encountered among
      women, and is the root of many gynecological disorders. Danggui Buxue Decoction
      (DBD), a classical traditional Chinese formula which is composed of Astragali
      Radix (AR) and Angelicae Sinensis Radix (ASR) at the ratio of 5:1 (w/w), is
      widely used in TCM clinics for treatment of blood deficiency syndrome. This study
      is to compare the in vivo pharmacokinetic properties of seven major bio-active
      components in normal and blood deficiency rats after oral administration of DBD.
      MATERIALS AND METHODS: Blood deficiency rats were induced by bleeding from orbit
      at the dosages of 5.0mL/kg each day for 12 days. Normal and blood deficiency rats
      were administrated of DBD on the 12th day at the dosage of 20g/kg, and blood was
      collected at different time points after then. Concentrations of ferulic acid,
      caffeic acid, butylphthalide, ligustilide, calycosin-7-O-beta-glucoside, ononin,
      and astragaloside IV in plasma were quantified by UPLC-TQ/MS, and the main
      pharmacokinetic parameters were calculated by DAS 2.0. RESULTS: It was found that
      Cmax, Tmax and MRT0~T of astragaloside IV, Cmax, T1/2Z, AUC0~T and MRT0~T of
      calycosin-7-O-beta-glucoside, T1/2Z and AUC0~T of ferulic acid, T1/2Z, AUC0~T and
      MRT0~T of ononin, and MRT0~T of ligustilide, butylphthalide, and caffeic acid in
      blood deficiency rats was significantly different (P<0.05) from normal rats.
      CONCLUSIONS: This study was the first report about pharmacokinetic investigation
      in blood deficiency animals which was conducted by bleeding. And the results
      demonstrated that the seven DBD constituents in normal and blood deficiency rats
      had obvious differences in some pharmacokinetic characteristics, suggesting that
      the rate and extent of drug metabolism were altered in blood deficiency animals.

PMID- 24583240
TI  - Anti-melanoma activity of Cynanchi atrati Radix is mediated by regulation of NF
      kappa B activity and pro-apoptotic proteins.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Cynanchi atrati Radix has been traditionally
      prescribed for patients with inflammatory fever or chronic tumoral disorders.
      Melanoma is one of the most devastating cancer types, in which overexpression of
      nuclear factor kappa B (NF-kappaB) enables the cancer to survive without
      apoptosis. To identify a potential anti-melanoma candidate, we evaluated the
      apoptotic activity of an ethanol extract of Cynanchi atrati Radix (CAE) on
      melanoma and its underlying mechanisms. MATERIALS AND METHODS: Sixty C57BL/6N
      mice with melanoma were orally administrated CAE (100 or 200mg/kg) or distilled
      water for 10 days. Survival, tumor weight and volume were monitored and measured.
      Intratumoral apoptotic change was measured using terminal deoxynucleotidyl
      transferase-mediated dUTP nick end labeling (TUNEL) staining. To confirm the pro
      apoptotic activity of CAE (10, 50 or 100MUg/mL) compared to positive drug
      (10MUg/mL of IKK-2 inhibitor IV), cell proliferation, caspase-3/7 activity, flow
      cytometric analysis, TUNEL and DAPI staining, immunoblotting and gene expression
      analyses for apoptosis-associated genes were conducted using B16F10 cell line.
      RESULTS: CAE administration remarkably improved survivability with a significant
      reduction in tumor weight (p<0.01) and volume (p<0.01), as well as increased
      apoptotic bodies in melanoma tissue. The CAE treatment significantly inhibited
      proliferation of B16F10 cells (p<0.001), but increased caspase-3/7 activity
      (p<0.01 or 0.001) and apoptotic population. The CAE partially blocked nuclear
      translocation of NF-kappaB but activated the p53-associated apoptotic pathway.
      CONCLUSION: These results indicate that the CAE has anti-melanoma potential, and
      the underlying mechanisms involve inhibition of the activities of NF-kappaB and
      its target proteins as well as promoting the activities of pro-apoptotic
      proteins.

PMID- 24583241
TI  - An ethnobotanical study of indigenous knowledge on medicinal plants used by the
      village peoples of Thoppampatti, Dindigul district, Tamilnadu, India.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: This study provides significant
      ethnopharmacological information, both qualitative and quantitative on medicinal
      plants in the Thoppampatti village, Dindigul district, Tamilnadu, India. There is
      urgency in recording such data to conserve the traditional medicinal plants. This
      is the first ethnobotanical study which records the traditional important
      medicinal plants of Thoppampatti village. To collect, analyze and evaluate the
      ethnopharmacologic knowledge in Thoppampatti village in order to protect it. This
      study reports the results of an ethnopharmacological survey on the uses of
      medicinal plants by inhabitants of the Thoppampatti. MATERIALS AND METHODS: The
      field study was carried out in a period of about one year (April 2012-May 2013)
      in Thoppampatti village. The information was obtained through open and semi
      structured interviews with 48 (27 males, 21 females) knowledgeable local people
      and traditional healers (THs). The collected data were analyzed qualitatively and
      quantitatively. In addition, use value (UV), relative importance (RI) and Jaccard
      index (JI) was determined. RESULTS: A total of 139 species of plants, mostly
      trees and herbs, belonging to 54 families were identified in this study. This is
      used to treat 142 diseases and ailments. These ailments were categorized into 18
      major categories. Leaves were the most frequently used parts, while decoction and
      juice are the most common method of preparation to treat various diseases. Based
      on IUCN Red data the identified medicinal plants include 11 least concerned
      species, 3 vulnerable species and one endangered species. The most important
      species according to their use value were Cynodon dactylon (0.79), Azadirachta
      indica (0.73), Ocimum tenuiflorum (0.71), Moringa oleifera (0.68), Coriandrum
      sativum (0.62), Abelmoschus esculentus (0.61), Acalypha indica (0.59) and
      Hibiscus rosa-sinensis (0.59). CONCLUSION: As a result of the present study,
      medicinal plants play an important role in the health care of Thoppampatti
      village inhabitants; they rely on medicinal plants to treat various ailments. In
      addition, the medicinal plants with high RI values might give some useful leads
      for further pharmacological investigations. Deforestation and overexploitation of
      a particular plant species leads to extinction so sustainable utilization of
      medicinal plants is recommended in the study area.

PMID- 24583242
TI  - Regioselective solvent-phase deuteration of polyphenolic compounds informs their
      identification by mass spectrometry.
AB  - Liquid chromatography-mass spectrometry (LC-MS) is a highly sensitive tool for
      the analysis of polyphenolic compounds in complex food and beverage matrices.
      However, the high degree of isomerism among polyphenols in general often
      complicates this approach, especially for identification of novel compounds.
      Here, we explore the utility of mild acid-catalyzed deuterium (MACD) labeling via
      electrophilic aromatic substitution as a complementary method for informing
      polyphenolic compound structure elucidation. To prevent hydrolysis of acid-labile
      glycosidic linkages, optimal reaction conditions that maximize regioselective
      hydrogen/deuterium (H/D) exchange of aromatic protons while preserving compound
      integrity were characterized (60 degrees C, pH 3.0, 72 h). Under these
      conditions, standard compounds varying in the number and position of hydroxyl,
      glycosyl, and methyl groups about their aromatic core structure produced
      distinguishable H/D exchange patterns. The applicability of this method for the
      analysis of complex mixtures was demonstrated in red wine where the extent of
      deuterium exchange, together with accurate mass information, led to the putative
      identification of an unknown compound. The identification was further supported
      by tandem MS (MS/MS) data, which matched conclusively to the same compound in the
      Metlin LC-MS/MS library. With the capacity to discriminate between select
      isomeric forms, MACD labeling provides structural information that complements
      accurate mass and tandem mass spectral measurements for informing the
      identification of polyphenolics by MS.

PMID- 24583243
TI  - Microplate-based screening for small molecule inhibitors of neuropilin-2/vascular
      endothelial growth factor-C interactions.
AB  - Vascular endothelial growth factor-C (VEGF-C) is a secreted growth factor
      essential for lymphangiogenesis. VEGF-C functions in both physiological and
      pathological lymphangiogenesis, particularly in tumor metastasis, making it an
      attractive therapeutic target. Members of two families of cell surface receptors
      transduce VEGF-C signals: neuropilin-2 (Nrp2) and VEGF-receptor (VEGFR)-2/3. Nrp2
      is a promising target for inhibition because it is highly expressed in lymphatic
      vessels. Here we describe a microplate-based assay for discovery of VEGF-C/Nrp2
      inhibitors. We optimize this assay for use in screening an inhibitor library and
      identify three novel Nrp2/VEGF-C binding inhibitors from the National Institutes
      of Health (NIH) Clinical Collection small molecule library. 

PMID- 24583244
TI  - Leukemia, lymphoma and multiple myeloma mortality (1950-1999) and incidence (1969
      1999) in the Eldorado uranium workers cohort.
AB  - Uranium workers are chronically exposed to low levels of radon decay products
      (RDP) and gamma (gamma) radiation. Risks of leukemia from acute and high doses of
      gamma-radiation are well-characterized, but risks from lower doses and dose-rates
      and from RDP exposures are controversial. Few studies have evaluated risks of
      other hematologic cancers in uranium workers. The purpose of this study was to
      analyze radiation-related risks of hematologic cancers in the cohort of Eldorado
      uranium miners and processors first employed in 1932-1980 in relation to
      cumulative RDP exposures and gamma-ray doses. The average cumulative RDP exposure
      was 100.2 working level months and the average cumulative whole-body gamma
      radiation dose was 52.2 millisievert. We identified 101 deaths and 160 cases of
      hematologic cancers in the cohort. Overall, male workers had lower mortality and
      cancer incidence rates for all outcomes compared with the general Canadian male
      population, a likely healthy worker effect. No statistically significant
      association between RDP exposure or gamma-ray doses, or a combination of both,
      and mortality or incidence of any hematologic cancer was found. We observed
      consistent but non-statistically significant increases in risks of chronic
      lymphocytic leukemia (CLL) and Hodgkin lymphoma (HL) incidence and non-Hodgkin
      lymphoma (NHL) mortality with increasing gamma-ray doses. These findings are
      consistent with recent studies of increased risks of CLL and NHL incidence after
      gamma-radiation exposure. Further research is necessary to understand risks of
      other hematologic cancers from low-dose exposures to gamma-radiation. 

PMID- 24583245
TI  - GLP-1 released to the mesenteric lymph duct in mice: effects of glucose and fat.
AB  - Using a newly developed in vivo model measuring glucagon-like peptide-1 (GLP-1)
      in gut lymphatics in mice, we quantified GLP-1 secretion in vivo after glucose
      versus fat ingestion with and without concomitant DPP-4 inhibition. The
      mesenteric lymphatic duct was cannulated in anesthetized C57BL6/J mice and lymph
      was collected in 30 min intervals. Glucose or fat emulsion (Intralipid(r)) (0.03,
      0.1 or 0.3 kcal) with or without DPP-4-inhibition (NVP DPP728; 10 MUmol/kg) was
      administered by gastric gavage. Basal intact GLP-1 levels were 0.37+/-0.04 pmol/l
      (n=61) in lymph compared to 0.07+/-0.03 in plasma (n=6; P=0.04) and basal DPP-4
      activity was 4.7+/-0.3 pmol/min/MUl in lymph (n=23) compared to 22.3+/-0.9
      pmol/min/MUl in plasma (n=8; P<0.001). Lymph flow increased from 1.2+/-0.1
      MUl/min to 2.3+/-02MUl/min at 30 min after glucose and fat administration, with
      no difference between type of challenge or dose (n=81). Lymph GLP-1 levels
      increased calorie-dependently after both glucose and fat but with different time
      courses in that glucose induced a transient increase which had returned to
      baseline after 90 min whereas the lipid induced a sustained increase which was
      still elevated above baseline after 210 min. Lymph GLP-1 appearance during 210
      min was two to three-fold higher after glucose (7.4+/-2.3 fmol at 0.3 kcal) than
      after isocaloric fat (2.9+/-0.8 fmol at 0.3 kcal; P<0.001). The slope between
      caloric load and lymph GLP-1 appearance was, however, identical after glucose and
      fat. We conclude that lymph GLP-1 is higher than plasma GLP-1 whereas lymph DPP-4
      activity is lower than plasma DPP-4 activity and that both glucose and fat
      clearly stimulate GLP-1 secretion calorie-dependently in vivo but with different
      time courses.

PMID- 24583246
TI  - A single secreted luciferase-based gene reporter assay.
AB  - Promoter analysis typically employs a reporter gene fused to a test promoter
      combined with a second reporter fused to a control promoter that is used for
      normalization purposes. However, this approach is not valid when experimental
      conditions affect the control promoter. We have developed and validated a single
      secreted luciferase reporter (SSLR) assay for promoter analysis that avoids the
      use of a control reporter. The approach uses an early level of expression of a
      secreted luciferase linked to a test promoter as an internal normalization
      control for subsequent analysis of the same promoter. Comparison of the SSLR
      assay with the dual luciferase reporter (DLR) assay using HMGCR (3-hydroxy-3
      methylglutaryl-coenzyme A reductase) and LDLR (low-density lipoprotein receptor)
      promoter constructs, which are down-regulated by 25-hydroxycholesterol, show that
      both assays yield similar results. Comparison of the response of the HMGCR
      promoter in SSLR transient assays compared very favorably with the response of
      the same promoter in the stable cell line. Overall, the SSLR assay proved to be a
      valid alternative to the DLR assay for certain applications and had significant
      advantages in that measurement of only one luciferase is required and monitoring
      can be continuous because cell lysis is not necessary. 

PMID- 24583247
TI  - Entecavir vs. lamivudine in chronic hepatitis B patients with severe acute
      exacerbation and hepatic decompensation.
AB  - BACKGROUND & AIMS: We compared the mortality and treatment response between
      lamivudine (LAM) and entecavir (ETV) in chronic hepatitis B (CHB) patients with
      severe acute exacerbation and hepatic decompensation. METHODS: From 2003 to 2010
      (the LAM group) and 2008 to 2010 (the ETV group), 215 and 107 consecutive CHB
      naive patients with severe acute exacerbation and hepatic decompensation treated
      with LAM and ETV respectively, were recruited. RESULTS: At baseline, the LAM
      group had higher AST levels and end-stage liver disease (MELD) scores, and lower
      albumin levels than the ETV group. Univariate analysis showed that the LAM group
      had a higher rate of overall (p=0.02) and liver-related mortality (p=0.052) at
      week 24 than the ETV group, including in patients with acute-on-chronic liver
      failure. Multivariate analysis showed that MELD scores, ascites, and hepatic
      encephalopathy were independent factors for overall and liver-related mortality
      at week 24. ETV or LAM treatment was not an independent factor for mortality in
      all patients or patients with acute-on-chronic liver failure. The best cut-off
      value of MELD scores were 24 for 24-week liver-related mortality. The ETV group
      achieved better virological response (HBV DNA <300 copies/ml) than the LAM group
      at week 24 (p=0.043) and 48 (p=0.007). The T1753C/A mutation was also an
      independent predictor associated with overall and liver-related mortality at week
      24. CONCLUSIONS: The choice between ETV and LAM was not an independent factor for
      mortality in CHB patients with acute exacerbation and hepatic decompensation.
      Patients with ascites, hepatic encephalopathy, and MELD scores ?24 were
      associated with poor outcome and should be considered for liver transplantation.

PMID- 24583248
TI  - A switch in the source of ATP production and a loss in capacity to perform
      glycolysis are hallmarks of hepatocyte failure in advance liver disease.
AB  - BACKGROUND & AIMS: The cause of hepatic failure in the terminal stages of chronic
      injury is unknown. Cellular metabolic adaptations in response to the
      microenvironment have been implicated in cellular breakdown. METHODS: To address
      the role of energy metabolism in this process we studied mitochondrial number,
      respiration, and functional reserve, as well as cellular adenosine-5'
      triphosphate (ATP) production, glycolytic flux, and expression of glycolysis
      related genes in isolated hepatocytes from early and terminal stages of cirrhosis
      using a model that produces hepatic failure from irreversible cirrhosis in rats.
      To study the clinical relevance of energy metabolism in terminal stages of
      chronic liver failure, we analyzed glycolysis and energy metabolism related gene
      expression in liver tissue from patients at different stages of chronic liver
      failure according to Child-Pugh classification. Additionally, to determine
      whether the expression of these genes in early-stage cirrhosis (Child-Pugh Class
      A) is related to patient outcome, we performed network analysis of publicly
      available microarray data obtained from biopsies of 216 patients with hepatitis C
      related Child-Pugh A cirrhosis who were prospectively followed up for a median of
      10years. RESULTS: In the early phase of cirrhosis, mitochondrial function and ATP
      generation are maintained by increasing energy production from glycolytic flux as
      production from oxidative phosphorylation falls. At the terminal stage of hepatic
      injury, mitochondria respiration and ATP production are significantly
      compromised, as the hepatocytes are unable to sustain the increased demand for
      high levels of ATP generation from glycolysis. This impairment corresponds to a
      decrease in glucose-6-phosphatase catalytic subunit and phosphoglucomutase 1.
      Similar decreased gene expression was observed in liver tissue from patients at
      different stages of chronic liver injury. Further, unbiased network analysis of
      microarray data revealed that expression of these genes was down regulated in the
      group of patients with poor outcome. CONCLUSIONS: An adaptive metabolic shift,
      from generating energy predominantly from oxidative phosphorylation to
      glycolysis, allows maintenance of energy homeostasis during early stages of liver
      injury, but leads to hepatocyte dysfunction during terminal stages of chronic
      liver disease because hepatocytes are unable to sustain high levels of energy
      production from glycolysis.

PMID- 24583249
TI  - qFibrosis: a fully-quantitative innovative method incorporating histological
      features to facilitate accurate fibrosis scoring in animal model and chronic
      hepatitis B patients.
AB  - BACKGROUND & AIMS: There is increasing need for accurate assessment of liver
      fibrosis/cirrhosis. We aimed to develop qFibrosis, a fully-automated assessment
      method combining quantification of histopathological architectural features, to
      address unmet needs in core biopsy evaluation of fibrosis in chronic hepatitis B
      (CHB) patients. METHODS: qFibrosis was established as a combined index based on
      87 parameters of architectural features. Images acquired from 25 Thioacetamide
      treated rat samples and 162 CHB core biopsies were used to train and test
      qFibrosis and to demonstrate its reproducibility. qFibrosis scoring was analyzed
      employing Metavir and Ishak fibrosis staging as standard references, and collagen
      proportionate area (CPA) measurement for comparison. RESULTS: qFibrosis
      faithfully and reliably recapitulates Metavir fibrosis scores, as it can identify
      differences between all stages in both animal samples (p<0.001) and human
      biopsies (p<0.05). It is robust to sampling size, allowing for discrimination of
      different stages in samples of different sizes (area under the curve (AUC): 0.93
      0.99 for animal samples: 1-16 mm(2); AUC: 0.84-0.97 for biopsies: 10-44 mm in
      length). qFibrosis can significantly predict staging underestimation in
      suboptimal biopsies (<15 mm) and under- and over-scoring by different
      pathologists (p<0.001). qFibrosis can also differentiate between Ishak stages 5
      and 6 (AUC: 0.73, p=0.008), suggesting the possibility of monitoring intra-stage
      cirrhosis changes. Best of all, qFibrosis demonstrates superior performance to
      CPA on all counts. CONCLUSIONS: qFibrosis can improve fibrosis scoring accuracy
      and throughput, thus allowing for reproducible and reliable analysis of
      efficacies of anti-fibrotic therapies in clinical research and practice.

PMID- 24583250
TI  - I(f) blocking potency of ivabradine is preserved under elevated endotoxin levels
      in human atrial myocytes.
AB  - Lower heart rate is associated with better survival in patients with multiple
      organ dysfunction syndrome (MODS), a disease mostly caused by sepsis. The
      benefits of heart rate reduction by ivabradine during MODS are currently being
      investigated in the MODIfY clinical trial. Ivabradine is a selective inhibitor of
      the pacemaker current If and since If is impaired by lipopolysaccharide (LPS,
      endotoxin), a trigger of sepsis, we aimed to explore If blocking potency of
      ivabradine under elevated endotoxin levels in human atrial cardiomyocytes.
      Treatment of myocytes with S-LPS (containing the lipid A moiety, a core
      oligosaccharide and an O-polysaccharide chain) but not R595 (an O-chain lacking
      LPS-form) caused If inhibition under acute and chronic septic conditions. The
      specific interaction of S-LPS but not R595 to pacemaker channels HCN2 and HCN4
      proves the necessity of O-chain for S-LPS-HCN interaction. The efficacy of
      ivabradine to block If was reduced under septic conditions, an observation that
      correlated with lower intracellular ivabradine concentrations in S-LPS- but not
      R595-treated cardiomyocytes. Computational analysis using a sinoatrial pacemaker
      cell model revealed that despite a reduction of If under septic conditions,
      ivabradine further decelerated pacemaking activity. This novel finding, i.e. If
      inhibition by ivabradine under elevated endotoxin levels in vitro, may provide a
      molecular understanding for the efficacy of this drug on heart rate reduction
      under septic conditions in vivo, e.g. the MODIfY clinical trial. 

PMID- 24583251
TI  - GLUT1 deficiency in cardiomyocytes does not accelerate the transition from
      compensated hypertrophy to heart failure.
AB  - The aim of this study was to determine whether endogenous GLUT1 induction and the
      increased glucose utilization that accompanies pressure overload hypertrophy
      (POH) are required to maintain cardiac function during hemodynamic stress, and to
      test the hypothesis that lack of GLUT1 will accelerate the transition to heart
      failure. To determine the contribution of endogenous GLUT1 to the cardiac
      adaptation to POH, male mice with cardiomyocyte-restricted deletion of the GLUT1
      gene (G1KO) and their littermate controls (Cont) were subjected to transverse
      aortic constriction (TAC). GLUT1 deficiency reduced glycolysis and glucose
      oxidation by 50%, which was associated with a reciprocal increase in fatty acid
      oxidation (FAO) relative to controls. Four weeks after TAC, glycolysis increased
      and FAO decreased by 50% in controls, but were unchanged in G1KO hearts relative
      to shams. G1KO and controls exhibited equivalent degrees of cardiac hypertrophy,
      fibrosis, and capillary density loss after TAC. Following TAC, in vivo left
      ventricular developed pressure was decreased in G1KO hearts relative to controls,
      but+dP/dt was equivalently reduced in Cont and G1KO mice. Mitochondrial function
      was equivalently impaired following TAC in both Cont and G1KO hearts. GLUT1
      deficiency in cardiomyocytes alters myocardial substrate utilization, but does
      not substantially exacerbate pressure-overload induced contractile dysfunction or
      accelerate the progression to heart failure. 

PMID- 24583253
TI  - The neural basis of the bystander effect--the influence of group size on neural
      activity when witnessing an emergency.
AB  - Naturalistic observation and experimental studies in humans and other primates
      show that observing an individual in need automatically triggers helping
      behavior. The aim of the present study is to clarify the neurofunctional basis of
      social influences on individual helping behavior. We investigate whether when
      participants witness an emergency, while performing an unrelated color-naming
      task in an fMRI scanner, the number of bystanders present at the emergency
      influences neural activity in regions related to action preparation. The results
      show a decrease in activity with the increase in group size in the left pre- and
      postcentral gyri and left medial frontal gyrus. In contrast, regions related to
      visual perception and attention show an increase in activity. These results
      demonstrate the neural mechanisms of social influence on automatic action
      preparation that is at the core of helping behavior when witnessing an emergency.

PMID- 24583252
TI  - Reactivity and regulation of motor responses in cocaine-exposed infants.
AB  - Effects of prenatal exposure to cocaine on the reactivity and regulation of the
      motor system of 825 four-month-old infants enrolled in the Maternal Lifestyle
      Study were examined. Videotaped assessments of 338 cocaine-exposed (CE) infants
      and 487 non-exposed comparison infants were coded by examiners masked to exposure
      status. Exposure status was determined by meconium assay and maternal self-report
      of prenatal cocaine use. Infants were presented with a series of 17 visual,
      auditory and tactile stimuli for 30-s each. Intensity and latency of limb
      movement responses on a subset of items were analyzed to test the following
      hypotheses: CE infants are more active in general; CE infants exhibit increased
      movement levels for a larger proportion of time in response to stimulation; the
      motor systems of CE infants are more reactive to stimulation (e.g., shorter
      latencies to respond); and CE infants are poorer regulators of the motor system.
      RESULTS: CE infants were not more active in general and data do not indicate a
      more highly reactive motor system. However, CE infants exhibited increased
      movement levels for a larger proportion of time in response to stimulation.
      Additional analysis of movement exhibited during three tactile items found
      increased movement lability in CE infants and different patterns of responding,
      suggesting that the effects of prenatal cocaine exposure on the motor system may
      vary by context. Covariate effects for tobacco, alcohol, and marijuana are also
      reported.

PMID- 24583254
TI  - Functional size of human visual area V1: a neural correlate of top-down
      attention.
AB  - Heavy demands are placed on the brain's attentional capacity when selecting a
      target item in a cluttered visual scene, or when reading. It is widely accepted
      that such attentional selection is mediated by top-down signals from higher
      cortical areas to early visual areas such as the primary visual cortex (V1).
      Further, it has also been reported that there is considerable variation in the
      surface area of V1. This variation may impact on either the number or specificity
      of attentional feedback signals and, thereby, the efficiency of attentional
      mechanisms. In this study, we investigated whether individual differences between
      humans performing attention-demanding tasks can be related to the functional area
      of V1. We found that those with a larger representation in V1 of the central 12
      degrees  of the visual field as measured using BOLD signals from fMRI were able
      to perform a serial search task at a faster rate. In line with recent suggestions
      of the vital role of visuo-spatial attention in reading, the speed of reading
      showed a strong positive correlation with the speed of visual search, although it
      showed little correlation with the size of V1. The results support the idea that
      the functional size of the primary visual cortex is an important determinant of
      the efficiency of selective spatial attention for simple tasks, and that the
      attentional processing required for complex tasks like reading are to a large
      extent determined by other brain areas and inter-areal connections.

PMID- 24583256
TI  - HTLV-I infection: a dynamic struggle between viral persistence and host immunity.
AB  - Human T-lymphotropic virus type I (HTLV-I) causes chronic infection for which
      there is no cure or neutralising vaccine. HTLV-I has been clinically linked to
      the development of adult T-cell leukaemia/lymphoma (ATL), an aggressive blood
      cancer, and HAM/TSP, a progressive neurological and inflammatory disease.
      Infected individuals typically mount a large, persistently activated CD8(+)
      cytotoxic T-lymphocyte (CTL) response against HTLV-I-infected cells, but
      ultimately fail to effectively eliminate the virus. Moreover, the identification
      of determinants to disease manifestation has thus far been elusive. A key issue
      in current HTLV-I research is to better understand the dynamic interaction
      between persistent infection by HTLV-I and virus-specific host immunity. Recent
      experimental hypotheses for the persistence of HTLV-I in vivo have led to the
      development of mathematical models illuminating the balance between proviral
      latency and activation in the target cell population. We investigate the role of
      a constantly changing anti-viral immune environment acting in response to the
      effects of infected T-cell activation and subsequent viral expression. The
      resulting model is a four-dimensional, non-linear system of ordinary differential
      equations that describes the dynamic interactions among viral expression,
      infected target cell activation, and the HTLV-I-specific CTL response. The global
      dynamics of the model is established through the construction of appropriate
      Lyapunov functions. Examining the particular roles of viral expression and host
      immunity during the chronic phase of HTLV-I infection offers important insights
      regarding the evolution of viral persistence and proposes a hypothesis for
      pathogenesis. 

PMID- 24583257
TI  - Preparation of hemocompatible cellulosic paper based on P(DMAPS)-functionalized
      surface.
AB  - The surface-modification of paper substrates with functional layers is gaining
      increasing interest, both from academic and industrial research. In this case,
      the cellulosic paper (CP) surface was functionalized with zwitterionic poly-(3
      dimethyl(methacryloyloxyethyl) ammoniumpropane sulfonate) (CP-g-P(DMAPS) via
      surface-initiated atom transfer radical polymerization (ATRP) technique for
      enhancing blood compatibility. An obvious increase in graft yield of the
      functional P(DMAPS) with polymerization time was observed. The new CP-g-P(DMAPS)
      produced was investigated for its hemocompatibility. The hemocompatibility
      studied including platelet and whole blood ceels adhesion tests, hemolysis assay,
      morphological changes of red blood cells (RBCs), coagulation time tests, and
      complement activation, platelet activation at the molecular level. Most assays
      had remarkable differences in the presence of the new zwitterionic CP, indicated
      the importance of the zwitterion for hemocompatibility of CP.

PMID- 24583255
TI  - A multivariate distance-based analytic framework for connectome-wide association
      studies.
AB  - The identification of phenotypic associations in high-dimensional brain
      connectivity data represents the next frontier in the neuroimaging connectomics
      era. Exploration of brain-phenotype relationships remains limited by statistical
      approaches that are computationally intensive, depend on a priori hypotheses, or
      require stringent correction for multiple comparisons. Here, we propose a
      computationally efficient, data-driven technique for connectome-wide association
      studies (CWAS) that provides a comprehensive voxel-wise survey of brain-behavior
      relationships across the connectome; the approach identifies voxels whose whole
      brain connectivity patterns vary significantly with a phenotypic variable. Using
      resting state fMRI data, we demonstrate the utility of our analytic framework by
      identifying significant connectivity-phenotype relationships for full-scale IQ
      and assessing their overlap with existent neuroimaging findings, as synthesized
      by openly available automated meta-analysis (www.neurosynth.org). The results
      appeared to be robust to the removal of nuisance covariates (i.e., mean
      connectivity, global signal, and motion) and varying brain resolution (i.e.,
      voxelwise results are highly similar to results using 800 parcellations). We show
      that CWAS findings can be used to guide subsequent seed-based correlation
      analyses. Finally, we demonstrate the applicability of the approach by examining
      CWAS for three additional datasets, each encompassing a distinct phenotypic
      variable: neurotypical development, Attention-Deficit/Hyperactivity Disorder
      diagnostic status, and L-DOPA pharmacological manipulation. For each phenotype,
      our approach to CWAS identified distinct connectome-wide association profiles,
      not previously attainable in a single study utilizing traditional univariate
      approaches. As a computationally efficient, extensible, and scalable method, our
      CWAS framework can accelerate the discovery of brain-behavior relationships in
      the connectome.

PMID- 24583259
TI  - Surface charge and hydrodynamic coefficient measurements of Bacillus subtilis
      spore by optical tweezers.
AB  - In this work we report on the simultaneous measurement of the hydrodynamic
      coefficient and the electric charge of single Bacillus subtilis spores. The
      latter has great importance in protein binding to spores and in the adhesion of
      spores onto surfaces. The charge and the hydrodynamic coefficient were measured
      by an accurate procedure based on the analysis of the motion of single spores
      confined by an optical trap. The technique has been validated using charged
      spherical polystyrene beads. The excellent agreement of our results with the
      expected values demonstrates the quality of our procedure. We measured the charge
      of spores of B. subtilis purified from a wild type strain and from two isogenic
      mutants characterized by an altered spore surface. Our technique is able to
      discriminate the three spore types used, by their charge and by their
      hydrodynamic coefficient which is related to the hydrophobic properties of the
      spore surface. 

PMID- 24583258
TI  - Improved double emulsion technology for fabricating autofluorescent microcapsules
      as novel ultrasonic/fluorescent dual-modality contrast agents.
AB  - The aim of this study is to explore an improved double emulsion technology with
      in situ reaction of lysine (Lys) and glutaraldehyde (GA) for fabricating
      autofluorescent Lys-poly(lactic-co-glycolic acid)-GA (Lys-PLGA-GA) microcapsules
      as novel ultrasonic/fluorescent dual-modality contrast agents. Scanning electron
      microscope (SEM) and static light scattering (SLS) results show that 80% of the
      Lys-PLGA-GA microcapsules are larger than 1.0 MUm and 90% of them are smaller
      than 8.9 MUm. SEM and laser confocal scanning microscope (LCSM) data demonstrate
      that the structure of our Lys-PLGA-GA microcapsules is hollow. Compared with the
      FT-IR spectrum of PLGA microcapsules, a new peak at 1,644 cm(-1) in that of Lys
      PLGA-GA microcapsules confirms the formed Schiff base in Lys-PLGA-GA
      microcapsules. LCSM images and fluorescence spectra show that our Lys-PLGA-GA
      microcapsules exhibit bright and stable autofluorescence without conjugation to
      any fluorescent agent, which can be ascribed to the n-pi transitions of the CN
      bonds in the formed Schiff base. Our autofluorescent Lys-PLGA-GA microcapsules
      might have more wide applications than traditional fluorescent dyes because their
      excitation and emission spectra are both broad. The fluorescence intensity can
      also be tuned by the feeding amount of Lys and GA. The MTT assays reveal that the
      autofluorescent microcapsules are biocompatible. The results of fluorescent
      imaging in cells and in vitro ultrasonic imaging demonstrate the feasibility of
      our autofluorescent Lys-PLGA-GA microcapsules as ultrasonic/fluorescent dual
      modality contrast agents. This novel ultrasonic/fluorescent dual-modality
      contrast agent might have potential for a variety of biological and medical
      applications.

PMID- 24583260
TI  - Galactosylated electrospun membranes for hepatocyte sandwich culture.
AB  - In this work, we developed a galactocylated electrospun polyurethane membrane for
      sandwich culture of hepatocyte sandwich culture. The electrospun fibrous
      membranes were bio-functionalized with galactose molecules by a UV-crosslinked
      layer-by-layer polyelectrolyte multilayer deposition technique. The
      galactosylated electrospun membranes were employed as a top support membrane for
      the sandwich culture of HepG2/C3A cells on a collagen substrate. Our results
      demonstrate that HepG2/C3A cells covered by the galactosylated PU membranes form
      multi-cellular aggregates and lead to improved albumin secretion ability compared
      to the control membranes (unmodified PU or poly(ethylene imine)-modified PU). Our
      study reveals the potential of galactosylated electrospun membranes in the
      application of liver tissue engineering and the regeneration of liver-tissue
      substitutes.

PMID- 24583261
TI  - Microarray meta-analysis identifies evolutionarily conserved BMP signaling
      targets in developing long bones.
AB  - In vertebrates, BMP signaling has been demonstrated to be sufficient for bone
      formation in several tissue contexts. This suggests that genes necessary for bone
      formation are expressed in a BMP signaling dependent manner. However, till date
      no gene has been reported to be expressed in a BMP signaling dependent manner in
      bone. Our aim was to identify such genes. On searching the literature we found
      that several microarray experiments have been conducted where the transcriptome
      of osteogenic cells in absence and presence of BMP signaling activation have been
      compared. However, till date, there is no evidence to suggest that any of the
      genes found to be upregulated in presence of BMP signaling in these microarray
      analyses is indeed a target of BMP signaling in bone. We wanted to utilize this
      publicly available information to identify candidate BMP signaling target genes
      in vivo. We performed a meta-analysis of six such comparable microarray datasets.
      This analysis and subsequent experiments led to the identification of five
      targets of BMP signaling in bone that are conserved both in mouse and chick. Of
      these Lox, Klf10 and Gpr97 are likely to be direct transcriptional targets of BMP
      signaling pathway. Dpysl3, is a novel BMP signaling target identified in our
      study. Our data demonstrate that Dpysl3 is important for osteogenic
      differentiation of mesenchymal cells and is involved in cell secretion. We have
      demonstrated that the expression of Dpysl3 is co-operatively regulated by BMP
      signaling and Runx2. Based on our experimental data, in silico analysis of the
      putative promoter-enhancer regions of Bmp target genes and existing literature,
      we hypothesize that BMP signaling collaborates with multiple signaling pathways
      to regulate the expression of a unique set of genes involved in endochondral
      ossification. 

PMID- 24583264
TI  - Edouard Kieffer 1942-2014.

PMID- 24583262
TI  - Ephrin-B2 governs morphogenesis of endolymphatic sac and duct epithelia in the
      mouse inner ear.
AB  - Control over ionic composition and volume of the inner ear luminal fluid
      endolymph is essential for normal hearing and balance. Mice deficient in either
      the EphB2 receptor tyrosine kinase or the cognate transmembrane ligand ephrin-B2
      (Efnb2) exhibit background strain-specific vestibular-behavioral dysfunction and
      signs of abnormal endolymph homeostasis. Using various loss-of-function mouse
      models, we found that Efnb2 is required for growth and morphogenesis of the
      embryonic endolymphatic epithelium, a precursor of the endolymphatic sac (ES) and
      duct (ED), which mediate endolymph homeostasis. Conditional inactivation of Efnb2
      in early-stage embryonic ear tissues disrupted cell proliferation, cell survival,
      and epithelial folding at the origin of the endolymphatic epithelium. This
      correlated with apparent absence of an ED, mis-localization of ES ion transport
      cells relative to inner ear sensory organs, dysplasia of the endolymph fluid
      space, and abnormally formed otoconia (extracellular calcite-protein composites)
      at later stages of embryonic development. A comparison of Efnb2 and Notch
      signaling-deficient mutant phenotypes indicated that these two signaling systems
      have distinct and non-overlapping roles in ES/ED development. Homozygous deletion
      of the Efnb2 C-terminus caused abnormalities similar to those found in the
      conditional Efnb2 null homozygote. Analyses of fetal Efnb2 C-terminus deletion
      heterozygotes found mis-localized ES ion transport cells only in the genetic
      background exhibiting vestibular dysfunction. We propose that developmental
      dysplasias described here are a gene dose-sensitive cause of the vestibular
      dysfunction observed in EphB-Efnb2 signaling-deficient mice. 

PMID- 24583265
TI  - Orai1 and STIM1 mediate SOCE and contribute to apoptotic resistance of pancreatic
      adenocarcinoma.
AB  - The store-operated calcium channels (SOCs) represent one of the major calcium
      entry pathways in non-excitable cells. SOCs and in particular their major
      components ORAI1 and STIM1 have been shown to be implicated in a number of
      physiological and pathological processes such as apoptosis, proliferation and
      invasion. Here we demonstrate that ORAI1 and STIM1 mediate store-operated calcium
      entry (SOCE) in pancreatic adenocarcinoma cell lines. We show that both ORAI1 and
      STIM1 play pro-survival anti-apoptotic role in pancreatic adenocarcinoma cell
      lines, as siRNA-mediated knockdown of ORAI1 and/or STIM1 increases apoptosis
      induced by chemotherapy drugs 5-fluorouracil (5-FU) or gemcitabine. We also
      demonstrate that both 5-FU and gemcitabine treatments increase SOCE in Panc1
      pancreatic adenocarcinoma cell line via upregulation of ORAI1 and STIM1.
      Altogether our results reveal the novel calcium-dependent mechanism of action of
      the chemotherapy drugs 5-FU and gemcitabine and emphasize the anti-apoptotic role
      of ORAI1 and STIM1 in pancreatic adenocarcinoma cells. This article is part of a
      Special Issue entitled: Calcium signaling in health and disease. Guest Editors:
      Geert Bultynck, Jacques Haiech, Claus W. Heizmann, Joachim Krebs, and Marc
      Moreau. 

PMID- 24583263
TI  - Cooperative interaction of Etv2 and Gata2 regulates the development of
      endothelial and hematopoietic lineages.
AB  - Regulatory mechanisms that govern lineage specification of the mesodermal
      progenitors to become endothelial and hematopoietic cells remain an area of
      intense interest. Both Ets and Gata factors have been shown to have important
      roles in the transcriptional regulation in endothelial and hematopoietic cells.
      We previously reported Etv2 as an essential regulator of vasculogenesis and
      hematopoiesis. In the present study, we demonstrate that Gata2 is co-expressed
      and interacts with Etv2 in the endothelial and hematopoietic cells in the early
      stages of embryogenesis. Our studies reveal that Etv2 interacts with Gata2 in
      vitro and in vivo. The protein-protein interaction between Etv2 and Gata2 is
      mediated by the Ets and Gata domains. Using the embryoid body differentiation
      system, we demonstrate that co-expression of Gata2 augments the activity of Etv2
      in promoting endothelial and hematopoietic lineage differentiation. We also
      identify Spi1 as a common downstream target gene of Etv2 and Gata2. We provide
      evidence that Etv2 and Gata2 bind to the Spi1 promoter in vitro and in vivo. In
      summary, we propose that Gata2 functions as a cofactor of Etv2 in the
      transcriptional regulation of mesodermal progenitors during embryogenesis. 

PMID- 24583266
TI  - Green coffee polyphenols do not attenuate features of the metabolic syndrome and
      improve endothelial function in mice fed a high fat diet.
AB  - We have investigated the effects of the major polyphenol in coffee, chlorogenic
      acid (CGA), on obesity, glucose intolerance, insulin resistance, systemic
      oxidative stress and endothelial dysfunction in a mouse model of the metabolic
      syndrome. Thirty C57BL6 mice were randomly divided into (n=10/group) (i) normal
      diet (ND), (ii) high fat diet (HFD), or (iii) high fat diet supplemented with
      0.5% w/w green coffee bean extract (GCE) rich in chlorogenic acid (HFD+GCE). The
      high fat diet consisted of 28% fat and all animals were maintained on their diets
      for 12 weeks. The mice fed a HFD and HFD+GCE displayed symptoms of the metabolic
      syndrome compared to their normal fed counterparts, although no endothelial
      dysfunction was detected in the abdominal aortas after 12 weeks. GCE did not
      attenuate HFD-induced obesity, glucose intolerance, insulin resistance or
      systemic oxidative stress. Furthermore, GCE did not protect against ex vivo
      oxidant (hypochlorous acid)-induced endothelial dysfunction.

PMID- 24583268
TI  - Methionine sulfoxide reductase B3 deficiency inhibits cell growth through the
      activation of p53-p21 and p27 pathways.
AB  - Methionine sulfoxide reductase B3 (MsrB3) is an oxidoreductase in the endoplasmic
      reticulum that catalyzes the stereospecific reduction of methionine-R-sulfoxide
      to methionine. Here, we report the critical role and mechanisms of MsrB3 in cell
      proliferation. The deletion of MsrB3 led to a significant decrease in cell
      proliferation in mouse embryonic fibroblast (MEF) cells. MsrB3-knockout MEF cells
      showed increased p53 protein levels, compared to wild-type MEF cells, which
      subsequently elevated the protein level of cyclin-dependent kinase inhibitor p21.
      In addition, MsrB3 deficiency enhanced the protein level of p27, another cell
      cycle regulator, and caused cell cycle arrest at the G1 stage. The inhibitory
      effect of MsrB3 deficiency on cell proliferation through the activation of p53
      p21 and p27 pathways was also confirmed in primary human dermal fibroblasts.
      Collectively, the data suggest that MsrB3 is a regulator of cell growth through
      the p53-p21 and p27 pathways. 

PMID- 24583267
TI  - In vivo changes in plasma coenzyme Q10, carotenoid, tocopherol, and retinol
      levels in children after computer tomography.
AB  - BACKGROUND: Low dose X-irradiation (IR) from computer tomography (CT) can
      generate free radicals, which can damage biologically relevant molecules and
      ultimately lead to cancer. These effects are especially concerning for children
      owing to their higher radiosensitivity and longer life expectancy than adults.
      The lipid phase micronutrients (LPM) coenzyme Q10, carotenoids, E vitamers, and
      vitamin A are potent radical scavengers that can act as intracellular
      antioxidants. METHODS: We investigated changes in circulating levels of these LPM
      in 17 children (0.25-6 y) undergoing medically indicated CT scans involving
      relatively low IR doses. Blood was drawn before and 1h after CT scans and
      analyzed using HPLC with electrochemical and UV/VIS detection. RESULTS: We found
      significant decreases (p<0.05) in post-CT plasma levels in several LPM which
      suggests that these LPM can serve as biodosimeters and may protect against damage
      from IR during clinical procedures such as CT. The strongest predictors for pre-
      to post-CT changes for many LPM were their baseline levels. CONCLUSION: Future
      larger studies are warranted to confirm our findings and to test whether high
      circulating antioxidant levels protect against IR damage in vivo with an ultimate
      goal of establishing prophylactic modalities for CT-induced IR damage.

PMID- 24583269
TI  - Canavalia ensiformis urease, Jaburetox and derived peptides form ion channels in
      planar lipid bilayers.
AB  - Ureases catalyze the hydrolysis of urea into NH3 and CO2. They are synthesized by
      plants, fungi and bacteria but not by animals. Ureases display biological
      activities unrelated to their enzymatic activity, i.e., platelet and neutrophil
      activation, fungus inhibition and insecticidal effect. Urease from Canavalia
      ensiformis (jack bean) is toxic to several hemipteran and coleopteran insects.
      Jaburetox is an insecticidal fragment derived from jack bean urease. Among other
      effects, Jaburetox has been shown to interact with lipid vesicles. In this work,
      the ion channel activity of C. ensiformis urease, Jaburetox and three deletion
      mutants of Jaburetox (one lacking the N-terminal region, one lacking the C
      terminal region and one missing the central beta-hairpin) were tested on planar
      lipid bilayers. All proteins formed well resolved, highly cation-selective
      channels exhibiting two conducting states whose conductance ranges were 7-18pS
      and 32-79pS, respectively. Urease and the N-terminal mutant of Jaburetox were
      more active at negative potentials, while the channels of the other peptides did
      not display voltage-dependence. This is the first direct demonstration of the
      capacity of C. ensiformis urease and Jaburetox to permeabilize membranes through
      an ion channel-based mechanism, which may be a crucial step of their diverse
      biological activities, including host defense. 

PMID- 24583270
TI  - Estimating the health effects of greenhouse gas mitigation strategies: addressing
      parametric, model, and valuation challenges.
AB  - BACKGROUND: Policy decisions regarding climate change mitigation are increasingly
      incorporating the beneficial and adverse health impacts of greenhouse gas
      emission reduction strategies. Studies of such co-benefits and co-harms involve
      modeling approaches requiring a range of analytic decisions that affect the model
      output. OBJECTIVE: Our objective was to assess analytic decisions regarding model
      framework, structure, choice of parameters, and handling of uncertainty when
      modeling health co-benefits, and to make recommendations for improvements that
      could increase policy uptake. METHODS: We describe the assumptions and analytic
      decisions underlying models of mitigation co-benefits, examining their effects on
      modeling outputs, and consider tools for quantifying uncertainty. DISCUSSION:
      There is considerable variation in approaches to valuation metrics, discounting
      methods, uncertainty characterization and propagation, and assessment of low
      probability/high-impact events. There is also variable inclusion of adverse
      impacts of mitigation policies, and limited extension of modeling domains to
      include implementation considerations. Going forward, co-benefits modeling
      efforts should be carried out in collaboration with policy makers; these efforts
      should include the full range of positive and negative impacts and critical
      uncertainties, as well as a range of discount rates, and should explicitly
      characterize uncertainty. We make recommendations to improve the rigor and
      consistency of modeling of health co-benefits. CONCLUSION: Modeling health co
      benefits requires systematic consideration of the suitability of model
      assumptions, of what should be included and excluded from the model framework,
      and how uncertainty should be treated. Increased attention to these and other
      analytic decisions has the potential to increase the policy relevance and
      application of co-benefits modeling studies, potentially helping policy makers to
      maximize mitigation potential while simultaneously improving health.

PMID- 24583272
TI  - Smoking and its risk factors in Chinese elementary and middle school students: a
      nationally representative sample study.
AB  - OBJECTIVE: The purpose of this study was to examine the prevalence of smoking in
      a nationally representative sample of Chinese elementary and middle school
      students and to investigate its risk factors from families and schools. METHOD:
      The data were from the National Children's Study of China (NCSC), in which 24,013
      fourth- to ninth-grade students were recruited from 100 counties in 31 provinces
      in China. Chi-square tests and one-way ANOVAs were used to analyze the
      relationships between smoking and the risk factors. Logistic regressions were
      used to calculate odds ratios. RESULTS: The prevalence of ever smokers and
      current smokers were 19.0% and 5.4%. Focusing on current smokers, boys, middle
      school students, rural students, boarding students, non-only children and those
      owning parents with low educational levels reported smoking significantly more
      than girls, elementary school students, urban students, non-boarding students,
      only children and those owning parents with high educational levels. Lower trust
      and support from teachers and higher parent-child conflict positively predicted
      both smoking and smoking frequency. Lower trust and support from classmates was
      associated with higher possibility of smoking. However, higher trust and support
      from classmates was associated with higher smoking frequency. Teacher smoking and
      friend smoking were only predictive of smoking, but not of smoking frequency.
      CONCLUSIONS: Boys, middle school students, rural students, boarding students, non
      only children and those owning parents with low educational levels need special
      attention. The most risk factors for smoking and smoking frequency were lower
      trust and support from teachers and higher parent-child conflict.

PMID- 24583271
TI  - Correlates of nonmedical use of stimulants and methamphetamine use in a national
      sample.
AB  - BACKGROUND: Despite chemical similarities, ADHD stimulants and methamphetamine
      have distinct use patterns in the community. This study compared the
      characteristics of nonmedical ADHD stimulants users and methamphetamine users in
      a household sample. METHODS: In data from the 2009-2011 National Survey on Drug
      Use and Health, adult and adolescent stimulant users were categorized into three
      mutually exclusive subgroups: nonmedical ADHD stimulant users only (STM users),
      methamphetamine users (METH users), and both nonmedical ADHD stimulant and
      methamphetamine users (STM/METH users). Multivariate logistic regression analyses
      identified the substance comorbidity, mental health, and deviant behavior
      characteristics associated with these three groups. RESULTS: Compared to
      adolescent STM users, STM/METH users were more likely to be female, younger and
      uninsured while METH users were more likely to be younger, in a minority group
      and from a higher-income family. Compared to adult STM users, METH and STM/METH
      users were more likely to be male, older, uninsured, no longer married, and to be
      from rural areas. Adolescent METH users were more likely than STM users to report
      illegal drug use while adult METH users were less likely to report prescription
      drug use than their STM user counterparts. Overall, adult and adolescent STM/METH
      users were more likely to report substance use, mental health problems and
      deviant behaviors compared to STM users. CONCLUSION: The characteristics of STM
      users differ from METH and STM/METH users, and their associations with substance
      use and psychiatric comorbidities differ by age. Findings have implications for
      understanding the risks for stimulant use in different age subgroups.

PMID- 24583273
TI  - The Spanish version of the Brief Young Adult Alcohol Consequences Questionnaire
      (B-YAACQ): a Rasch model analysis.
AB  - The present work was aimed at analyzing the psychometric properties of the
      Spanish Brief YAACQ in a sample of Argentinean college students applying the Item
      Response Theory. Participants were 302 college students (59.9% females) who
      reported drinking alcohol within the last month. The B-YAACQ was translated into
      Spanish and the psychometric properties of this Spanish version were analyzed
      applying the Rasch Model, as well as testing group difference and conducting
      correlational analyses. The verification of the global fit of the data showed
      adequate indexes for the persons and items. The reliability estimate of the items
      was very high (.97), while the reliability estimate of the persons was modest
      (.65). All but one item had adequate fit indexes. B-YAACQ scores were strongly
      related to measures of hazardous alcohol drinking, including frequency of
      drunkenness episodes and frequency of heavy episodic drinking, indicating
      concurrent validity. The item content along the severity continuum was fairly
      similar to that found with US and Dutch samples. Three items had a gender bias
      against men and another three items showed a gender bias against women,
      indicating the presence of differential item functioning cancellation. The map of
      items and persons suggests that these 24 items do not provide a full coverage of
      the continuum of alcohol problems at the lower levels of the continuum. Overall,
      results from the present study suggest that the Spanish B-YAACQ offers a brief
      and efficient way to identify alcohol problems in Spanish-speaking college
      students.

PMID- 24583274
TI  - Integrated smoking cessation and binge drinking intervention for young adults: a
      pilot efficacy trial.
AB  - Alcohol consumption is strongly associated with cigarette smoking in young
      adults. The primary aim of this investigation was to complete a pilot evaluation
      of the efficacy of an integrated intervention that targets both cigarette smoking
      and binge drinking on the cigarette smoking and binge behavior of young adults at
      6-month follow-up. Participants were 95 young adult (M=24.3; SD=3.5 years)
      smokers (>=1 cigarettes per day) who binge drink (>=1 time per month) and who
      were randomly assigned to standard treatment (n=47) involving six individual
      treatment visits plus eight weeks of nicotine patch therapy or the identical
      smoking cessation treatment integrated with a binge drinking intervention
      (integrated intervention; n=48). Using an intent-to-treat analysis for tobacco
      abstinence, at both 3 month end of treatment and 6 month follow-up, more
      participants who received integrated intervention were biochemically confirmed
      abstinent from tobacco than those who received standard treatment at 3 months
      (19% vs. 9%, p=0.06) and 6 months (21% vs. 9%, p=0.05). At 6 months, participants
      who completed the study and who received integrated intervention consumed fewer
      drinks per month (p<0.05) and number of binge drinking episodes per month
      (p<0.05) than those who received standard treatment. Preliminary data supports
      that integrated intervention enhances smoking cessation and reduces binge
      drinking compared to standard treatment.

PMID- 24583275
TI  - Gambling and sexual behaviors in African-American adolescents.
AB  - OBJECTIVES: Late adolescence represents a developmental risk period when many
      youth become involved in multiple forms of high-risk behaviors with adverse
      consequences. This study assessed the degree to which two such behaviors,
      adolescent sexual behaviors and gambling, were associated in a community-based
      sample with a large African-American presence. STUDY DESIGN: Data are derived
      from a cohort study. This study focuses on 427 African-American participants with
      complete information on gambling and sexual behaviors by age 18 (72% of original
      cohort). Gambling involvement and related problems were based on responses to the
      South Oaks Gambling Screen - Revised for Adolescents. Several questions assessed
      sexual behaviors, including age of initiation. Multivariable logistic regression
      models adjusted for demographics, intervention status, impulsivity, depressive
      and anxiety symptoms, and alcohol and illegal drug use. RESULTS: Almost half of
      the sample (49%, n=211) had gambled at least once before age 18. More gamblers
      than non-gamblers had initiated sexual intercourse by age 18 (aOR: 2.29 [1.16,
      4.52]). Among those who had initiated sexual activity, more gamblers than non
      gamblers with high impulsivity levels at age 13 (vs. low impulsivity levels) had
      become pregnant or had impregnated someone. Among those who had initiated sexual
      activity by age 18, more male gamblers had impregnated someone by age 18 as
      compared to female gamblers becoming pregnant. CONCLUSIONS: Gambling and sexual
      behaviors often co-occur among adolescents. Such findings prompt the need for the
      inclusion of gambling, an often overlooked risky behavior, in behavioral
      prevention/intervention programs targeting adolescents.

PMID- 24583276
TI  - Psychometric development of the Problematic Pornography Use Scale.
AB  - Despite the increased social acceptance and widespread use of pornography over
      the past few decades, reliable and valid instruments assessing problematic use of
      pornography are lacking. This paper reports the findings of three studies aimed
      at developing and validating a new scale measuring problematic pornography use.
      The Problematic Pornography Use Scale (PPUS) items showed high internal
      consistency, convergent validity, and construct validity. Exploratory and
      confirmatory factor analyses revealed four core factors relating to proposed
      domains of problematic pornography use. High PPUS scores were positively
      correlated with measures of psychopathology, low self-esteem and poor attachment.
      Although PPUS scores were related to other behavioral addictions, problematic
      pornography use as operationalized in the current paper appears to be uniquely
      distinguished from features of behavioral addictions relating to gambling and
      Internet use. Findings highlight the potential use of the PPUS for future
      research and possible clinical applications by defining problematic pornography
      use as a behavioral addiction. 

PMID- 24583277
TI  - Moderating effects of positive parenting and maternal alcohol use on emerging
      adults' alcohol use: does living at home matter?
AB  - Positive parenting behaviors and parental modeling of alcohol use are consistent
      predictors of offspring's alcohol use. Recent research extends these findings to
      emerging adult children and confirms continued parental influence beyond
      adolescence. This paper examines how maternal warmth and supervision moderate the
      effects of mother's heavy alcohol use on their offspring's alcohol use among a
      sample of non-college-attending emerging adults. Three-way interactions were used
      to examine if these moderating effects differed between emerging adults who lived
      at home and those with other living arrangements. Separate analyses within gender
      were used to further examine these associations. Participants were 245 emerging
      adults between ages 18 and 22 years with no post-secondary education (59% female)
      who were selected from a national probability-based internet panel. Path analyses
      indicated that, regardless of living arrangements, male emerging adults who were
      more likely to witness their mother getting drunk were themselves more likely to
      engage in risky drinking. However, among female emerging adults, similarity
      between mothers' and daughters' drunkenness was strongest among participants who
      resided with their family and also reported low levels of maternal warmth. This
      study extends previous research by indicating that the effects of maternal
      modeling of heavy alcohol use on emerging adults' heavy alcohol use depend upon
      several factors, including the gender of the child and the family context.
      Implications of the study findings are discussed in terms of expanding the scope
      of a parent-based intervention (PBI) to all emerging adults, including those who
      do not attend colleges or universities.

PMID- 24583279
TI  - Role of extracellular signal-regulated kinases 1 and 2 and p38 mitogen-activated
      protein kinase pathways in regulating replication of Penicillium marneffei in
      human macrophages.
AB  - Penicillium marneffei (P. marneffei) is a human pathogen which persists in
      macrophages and threatens the immunocompromised patients. To elucidate the
      mechanisms involved, we investigated the role of extracellular signal-regulated
      kinases 1 and 2 (ERK1/2) and p38 mitogen-activated protein kinase (p38) pathways
      in cytokine expression, phagosome-lysosome fusion and replication of P. marneffei
      in P. marneffei-infected human macrophages. Analysis of both ERK1/2 and p38
      showed rapid phosphorylation in response to P. marneffei. Using specific
      inhibitors of p38 (SB203580) and MAP kinase kinase-1 (PD98059), we found that
      ERK1/2 and p38 were essential for P. marneffei-induced tumor necrosis factor
      alpha production, whereas p38, but not that of ERK, was essential for IL-10
      production. Furthermore, the presence of PD98059 always decreased phagosomal
      acidification and maturation and increased intracellular multiplication of P.
      marneffei, whereas the use of SB203580 always increased phagosomal acidification
      and maturation and decreased intracellular replication. These data suggest that a
      proper balance of between ERK1/2 and p38 may play an important role in
      controlling the replication of P. marneffei. Our findings further indicate a
      novel therapeutic avenue for treating P. marneffei by stimulating ERK1/2 or
      activating ERK1/2-dependent mechanisms. 

PMID- 24583278
TI  - A critical review of social and structural conditions that influence HIV risk
      among Mexican deportees.
AB  - Mexican migrants who are deported from the US may be at elevated risk for HIV
      infection. Deportations of Mexican migrants by the US have reached record
      numbers. We critically reviewed existing literature to assess how social and
      structural conditions in post-deportation settings can influence Mexican deported
      migrants' HIV risk. We also identify critical research gaps and make research
      recommendations. 

PMID- 24583280
TI  - The role of anti-apoptotic protein kinase Calpha in response to hypericin
      photodynamic therapy in U-87 MG cells.
AB  - Hypericin photodynamic therapy (HypPDT) has been found to be an efficient inducer
      of cell death. However, there are indications that HypPDT also activates rescuing
      pathways. Cell responses to HypPDT are highly dependent on the Hyp intracellular
      localization and accumulation. We have shown previously that in U87 MG cells Hyp
      localizes mostly in ER and partially in mitochondria, lysosomes and Golgi, and
      that HypPDT resulted primarily in apoptosis via the mitochondrial apoptotic
      pathway. We have also shown that Hyp co-localizes and interacts with anti
      apoptotic PKCalpha in U87 MG cells. To follow up on our previous work, we
      investigated how HypPDT influences PKCalpha in U87 MG cells. Here, we show that
      majority of PKCalpha present in U87 MG cells is already in a catalytically
      competent form phosphorylated at Thr638, and it is a likely Bcl2 kinase. The
      presence of Hyp itself does not affect PKCalpha distribution. HypPDT acute effect
      caused PKCalpha activation and translocation along the plasma membrane and
      partially in the nuclei. The prolonged effect of HypPDT, 5 and 24h post PDT,
      results in PKCalpha located predominantly in cytosol and nuclei. Moreover, we
      have shown that phosphorylated catalytically competent PKCalpha is critical for
      U87 glioma cell viability in response to HypPDT treatment. 

PMID- 24583281
TI  - Photodynamic inactivation of enveloped virus in protein plasma preparations by
      solid-phase fullerene-based photosensitizer.
AB  - BACKGROUND: The problem of transfusion-transmitted infections still remains
      serious and actual for health care despite the detailed testing of donors. Human
      immunodeficiency virus, hepatitis B and C viruses and human cytomegalovirus are
      among the most dangerous pathogens that can be transmitted with blood.
      Previously, a composition consisting of fullerene layer applied on silica gel
      particles was shown to inactivate influenza virus up to complete loss of
      infectivity. METHODS: In the present study the unit has been developed with
      source of irradiation whose spectrum is appropriate for solid-phase fullerene.
      The ability of the unit to inactivate the enveloped influenza virus in protein
      fraction of donor blood has been studied. RESULTS: It was shown that at optimized
      conditions complete inactivation of enveloped virus of extremely high initial
      titer (7.0-9.5 log 10 EID 50/0.2 mL) in the solution of albumin was achieved
      after as short time as 30 min of irradiation. This process did not affect the
      oxidative metabolism of neutrophils and membranes of erythrocytes evaluated by
      NBT reduction test and morphological analysis of erythrocytes, respectively.
      CONCLUSION: The data obtained suggests that the method described can be
      recommended for further development and optimization of the procedure of
      inactivation of viruses in the preparations of the plasma of donor blood.

PMID- 24583282
TI  - A systems wide mass spectrometric based linear motif screen to identify dominant
      in-vivo interacting proteins for the ubiquitin ligase MDM2.
AB  - Linear motifs mediate protein-protein interactions (PPI) that allow expansion of
      a target protein interactome at a systems level. This study uses a proteomics
      approach and linear motif sub-stratifications to expand on PPIs of MDM2. MDM2 is
      a multi-functional protein with over one hundred known binding partners not
      stratified by hierarchy or function. A new linear motif based on a MDM2
      interaction consensus is used to select novel MDM2 interactors based on Nutlin-3
      responsiveness in a cell-based proteomics screen. MDM2 binds a subset of peptide
      motifs corresponding to real proteins with a range of allosteric responses to
      MDM2 ligands. We validate cyclophilin B as a novel protein with a consensus MDM2
      binding motif that is stabilised by Nutlin-3 in vivo, thus identifying one of the
      few known interactors of MDM2 that is stabilised by Nutlin-3. These data invoke
      two modes of peptide binding at the MDM2 N-terminus that rely on a consensus core
      motif to control the equilibrium between MDM2 binding proteins. This approach
      stratifies MDM2 interacting proteins based on the linear motif feature and
      provides a new biomarker assay to define clinically relevant Nutlin-3 responsive
      MDM2 interactors. 

PMID- 24583283
TI  - A novel insulin receptor-signaling platform and its link to insulin resistance
      and type 2 diabetes.
AB  - Insulin-induced insulin receptor (IR) tyrosine kinase activation and insulin cell
      survival responses have been reported to be under the regulation of a membrane
      associated mammalian neuraminidase-1 (Neu1). The molecular mechanism(s) behind
      this process is unknown. Here, we uncover a novel Neu1 and matrix
      metalloproteinase-9 (MMP-9) cross-talk in alliance with neuromedin B G-protein
      coupled receptor (GPCR), which is essential for insulin-induced IR activation and
      cellular signaling. Neu1, MMP-9 and neuromedin B GPCR form a complex with IRbeta
      subunit on the cell surface. Oseltamivir phosphate (Tamiflu(r)), anti-Neu1
      antibodies, broad range MMP inhibitors piperazine and galardin (GM6001), MMP-9
      specific inhibitor (MMP-9i), and GPCR neuromedin B specific antagonist BIM-23127
      dose-dependently inhibited Neu1 activity associated with insulin stimulated rat
      hepatoma cells (HTCs) that overly express human IRs (HTC-IR). Tamiflu, anti-Neu1
      antibodies and MMP-9i attenuated phosphorylation of IRbeta and insulin receptor
      substrate-1 (IRS1) associated with insulin-stimulated cells. Olanzapine, an
      antipsychotic agent associated with insulin resistance, induced Neu3 sialidase
      activity in WG544 or 1140F01 human sialidosis fibroblast cells genetically
      defective in Neu1. Neu3 antagonist 2-deoxy-2,3-didehydro-N-acetylneuraminic acid
      (DANA) and anti-Neu3 antibodies inhibited sialidase activity associated with
      olanzapine treated murine Neu4 knockout macrophage cells. Olanzapine attenuated
      phosphorylation of IGF-R and IRS1 associated with insulin-stimulated human wild
      type fibroblast cells. Our findings identify a novel insulin receptor-signaling
      platform that is critically essential for insulin-induced IRbeta tyrosine kinase
      activation and cellular signaling. Olanzapine-induced Neu3 sialidase activity
      attenuated insulin-induced IGF-R and IRS1 phosphorylation contributing to insulin
      resistance. 

PMID- 24583284
TI  - Phosphorylation of DEP-1/PTPRJ on threonine 1318 regulates Src activation and
      endothelial cell permeability induced by vascular endothelial growth factor.
AB  - The protein tyrosine phosphatase DEP-1/PTPRJ positively regulates Src family
      kinases and critical biological functions in endothelial and hematopoietic cells.
      Phosphorylation of DEP-1 on Y1311/Y1320 mediates the association and activation
      of Src, and promotes Src-dependent angiogenic responses including endothelial
      cell permeability. We have identified T1318 as a phosphorylated residue proximal
      to Y1320. The aim of this study was to determine if T1318 phosphorylation exerts
      a regulatory role over the function of DEP-1. We show that phosphorylation of DEP
      1 on Y1320 was reduced when T1318 was mutated. This led to the decreased
      association of DEP-1 T1318A with Src, and defective Src activation in both HEK
      293T and VEGF-stimulated endothelial cells. Consistent with these findings, VEGF
      induced tyrosine phosphorylation of VE-cadherin, its association to beta
      arrestin1/2, and cell permeability were impaired in cells expressing DEP-1
      T1318A. Conversely, expression of the phosphomimetic mutant DEP-1 T1318E
      constitutively enhanced the phosphorylation of Y1320 and VE-cadherin over that
      induced by WT DEP-1, and resulted in increased VEGF-dependent permeability. DEP-1
      T1318 is part of a CK2 consensus phosphorylation site and was identified as a CK2
      substrate. Modulation of CK2 expression or activity in endothelial cells
      regulated T1318 phosphorylation, and correlated with the status of Y1320
      phosphorylation, Src activation, and cell permeability. CK2-dependent
      phosphorylation of DEP-1 T1318 promotes Y1320 phosphorylation and Src activation
      upon VEGF stimulation. Phosphorylation of T1318 is thus part of a regulatory
      mechanism that channels the activity of DEP-1 towards Src to allow its optimal
      activation and the promotion of endothelial cell permeability. 

PMID- 24583285
TI  - Toxoplasma gondii inhibits apoptosis via a novel STAT3-miR-17-92-Bim pathway in
      macrophages.
AB  - In order to accomplish their life cycles, intracellular pathogens, including the
      apicomplexan Toxoplasma gondii, subvert the innate apoptotic response of infected
      host cells. However, the precise mechanisms of parasite interference with the
      apoptotic pathway remain unclear. MicroRNAs (miRNAs) regulate gene expression at
      the posttranscriptional level. Using T. gondii strain TgCtwh3, which was isolated
      from felids and possesses the predominant genotype China 1 (ToxoDB(#)9) in China,
      we analyzed the miRNA expression profile of human macrophages challenged with
      TgCtwh3. The results showed that miR-17-92 miRNA expression was significantly
      increased and Bim was decreased in TgCtwh3-infected cells. Database analysis of
      miR-17-92 miRNAs revealed the potential binding sites in the 3'UTR of Bim, one of
      the crucial effectors of pro-apoptosis. Furthermore, we demonstrated that the
      promoter of the miR-17-92 gene cluster which encodes miRNAs was transactivated
      through the promoter binding of the STAT3 following TgCtwh3 infection. Taken
      together, we describe a novel STAT3-miR-17-92-Bim pathway, thus providing a
      mechanistic explanation for inhibition of apoptosis of host cells following
      Toxoplasma infection. 

PMID- 24583287
TI  - Role of dihydroxyacetone kinases I and II in the dha regulon of Klebsiella
      pneumoniae.
AB  - Dha regulon is responsible for anaerobic glycerol metabolism and 1,3-propanediol
      production in Klebsiella pneumoniae. DhaK encodes an ATP-dependent
      dihydroxyacetone kinase I, whereas dhaK123 encodes a dihydroxyacetone kinase II
      that uses phosphoenolpyruvate as a phosphate donor. The functions of
      dihydroxyacetone kinases I and II in K. pneumoniae have not been discriminated.
      In this study, four individual genes of the two kinases were knocked out, and the
      metabolic characteristics of these mutants were investigated. DhaK1 or dhaK2
      mutation inhibited dha regulon expression. DhaK3 mutation reduced glycerol
      utilization, and the growth was slower than the wild stain. However, dhaK
      mutation exerted no significant effects on glycerol metabolism. The metabolic
      characteristics of these mutants showed that the subunits of dihydroxyacetone
      kinase II were involved in the regulation of dha regulon expression, similar to
      the dha regulon of E. coli. Dihydroxyacetone kinase II catalyzed dihydroxyacetone
      conversion to dihydroxyacetone phosphate, whereas dihydroxyacetone kinase I
      showed no significant contribution to this reaction. 

PMID- 24583288
TI  - Ribosomal proteins: toward a next generation standard for prokaryotic
      systematics?
AB  - The seminal work of Carl Woese and co-workers has contributed to promote the RNA
      component of the small subunit of the ribosome (SSU rRNA) as a "gold standard" of
      modern prokaryotic taxonomy and systematics, and an essential tool to explore
      microbial diversity. Yet, this marker has a limited resolving power, especially
      at deep phylogenetic depth and can lead to strongly biased trees. The ever-larger
      number of available complete genomes now calls for a novel standard dataset of
      robust protein markers that may complement SSU rRNA. In this respect,
      concatenation of ribosomal proteins (r-proteins) is being growingly used to
      reconstruct large-scale prokaryotic phylogenies, but their suitability for
      systematic and/or taxonomic purposes has not been specifically addressed. Using
      Proteobacteria as a case study, we show that amino acid and nucleic acid r
      protein sequences contain a reliable phylogenetic signal at a wide range of
      taxonomic depths, which has not been totally blurred by mutational saturation or
      horizontal gene transfer. The use of accurate evolutionary models and
      reconstruction methods allows overcoming most tree reconstruction artefacts
      resulting from compositional biases and/or fast evolutionary rates. The inferred
      phylogenies allow clarifying the relationships among most proteobacterial orders
      and families, along with the position of several unclassified lineages,
      suggesting some possible revisions of the current classification. In addition, we
      investigate the root of the Proteobacteria by considering the time-variation of
      nucleic acid composition of r-protein sequences and the information carried by
      horizontal gene transfers, two approaches that do not require the use of an
      outgroup and limit tree reconstruction artefacts. Altogether, our analyses
      indicate that r-proteins may represent a promising standard for prokaryotic
      taxonomy and systematics. 

PMID- 24583289
TI  - The incidence of species-level paraphyly in animals: a re-assessment.
AB  - Species-level paraphyly was found by Funk and Omland (2003) to occur in 23% of
      animal species on the basis of a meta-analysis of published mitochondrial gene
      trees. Given the potential for bias in the selection of study organisms and the
      subsequent publication of their gene trees, I re-estimated the incidence of
      paraphyly in an independent dataset of publicly accessible COI sequences from the
      Barcode of Life Data System. Among 7368 animal species represented by two or more
      sequences, 19% were paraphyletic, slightly less than in the previous study. Rates
      within major taxonomic groups mirrored, but were slightly lower than, that
      observed earlier. Tests were made for operational factors that could inflate, and
      sampling effects that could underestimate, the rate of paraphyly. Overall the
      previous findings are confirmed. The observed incidence suggests that on average
      animal species diverged 2-3 Ne generations in the past, far short of the
      predicted 5 Ne generations required for complete monophyly. 

PMID- 24583286
TI  - Implications of non-canonical G-protein signaling for the immune system.
AB  - Heterotrimeric guanine nucleotide-binding proteins (G proteins), which consist of
      three subunits alpha, beta, and gamma, function as molecular switches to control
      downstream effector molecules activated by G protein-coupled receptors (GPCRs).
      The GTP/GDP binding status of Galpha transmits information about the ligand
      binding state of the GPCR to intended signal transduction pathways. In immune
      cells heterotrimeric G proteins impact signal transduction pathways that
      directly, or indirectly, regulate cell migration, activation, survival,
      proliferation, and differentiation. The cells of the innate and adaptive immune
      system abundantly express chemoattractant receptors and lesser amounts of many
      other types of GPCRs. But heterotrimeric G-proteins not only function in
      classical GPCR signaling, but also in non-canonical signaling. In these pathways
      the guanine exchange factor (GEF) exerted by a GPCR in the canonical pathway is
      replaced or supplemented by another protein such as Ric-8A. In addition, other
      proteins such as AGS3-6 can compete with Gbetagamma for binding to GDP bound
      Galpha. This competition can promote Gbetagamma signaling by freeing Gbetagamma
      from rapidly rebinding GDP bound Galpha. The proteins that participate in these
      non-canonical signaling pathways will be briefly described and their role, or
      potential one, in cells of the immune system will be highlighted. 

PMID- 24583290
TI  - Seven-locus molecular phylogeny of Myctophiformes (Teleostei; Scopelomorpha)
      highlights the utility of the order for studies of deep-sea evolution.
AB  - Fishes of the order Myctophiformes (Teleostei; Scopelomorpha) comprise over half
      of all deep-sea biomass, and are a critical component of marine ecosystems
      worldwide. Members of the family Myctophidae, within Myctophiformes, form the
      majority of species diversity within the order (~250 species, 33 genera, 2
      subfamilies), and are further known for their diverse bioluminescent traits,
      comprised of distinct cranial, postcranial, and caudal luminous systems that is
      perhaps the most elaborate among all vertebrates. These features make myctophids
      particularly compelling from both economic and scientific perspectives, yet no
      studies have sampled these fishes at a density appropriate for addressing any
      questions requiring a phylogenetic hypothesis as input. This study therefore
      presents a seven-locus molecular phylogeny of the order, sampling over 50% of all
      nominal myctophid species. This taxon sampling triples the representation of the
      next most comprehensive analysis, and reveals several new and well-supported
      hypotheses of relationships, in addition to supporting traditional hypotheses
      based on combined morphological data. This analysis shows that the slendertailed
      myctophids Gonichthys, Centrobranchus, Loweina, and Tarletonbeania are rendered
      non-monophyletic by a polyphyletic Myctophum; the enigmatic, monotypic genus
      Notolychnus valdiviae is nested within tribe Lampanyctini; the genus Diaphus is
      divided into at least two clades, with the suborbital (So) group recovered as
      monophyletic with strong support; and the genera Lampanyctus and Nannobrachium
      are recovered as non-monophyletic. These molecular results highlight the
      potential of myctophids as a premier model system for the application of modern
      comparative methods to studies of deep-sea evolution. 

PMID- 24583292
TI  - Comparative safety of the antifouling compound butenolide and 4,5-dichloro-2-n
      octyl-4-isothiazolin-3-one (DCOIT) to the marine medaka (Oryzias melastigma).
AB  - This study evaluated the potential adverse effects of butenolide, a promising
      antifouling compound, using the marine medaka (Oryzias melastigma), a model fish
      for marine ecotoxicology. The active ingredient used in the commercial
      antifoulant SeaNine 211, 4,5-dichloro-2-n-octyl-4-isothiazolin-3-one (DCOIT) was
      employed as the positive control. Adult marine medaka (4-month-old) were exposed
      to various concentrations of butenolide or DCOIT for 28 days and then depurated
      in clean seawater for 14 days (recovery). A suite of sensitive biomarkers,
      including hepatic oxidative stress, neuronal signal transmission, endocrine
      disruption, and reproductive function, was used to measure significant biological
      effects induced by the chemicals. Compared to DCOIT, chronic exposure to
      butenolide induced a lower extent of oxidative stress in the liver of male and
      female medaka. Furthermore, butenolide-exposed fish could recover faster from
      oxidative stress than fish exposed to DCOIT. Regarding neurotransmission, DCOIT
      significantly inhibited acetylcholinesterase (AChE) activity in the brain of both
      male and female medaka, whereas this was not significant for butenolide. In
      addition, plasma estradiol (E2) level was elevated and testosterone (T) level was
      decreased in male medaka exposed to DCOIT. This greatly imbalanced sex hormones
      ratio (E2/T) in exposed males, indicating that DCOIT is a potent endocrine
      disruptive chemical. In contrast, butenolide induced only moderate effects on sex
      hormone levels in exposed males, which could be gradually recovered during
      depuration. Moreover, the endocrine disruptive effect induced by butenolide did
      not affect normal development of offspring. In contrast, DCOIT-exposed fish
      exhibited a decrease of egg production and impaired reproductive success.
      Overall, the above findings demonstrated that chronic exposure to butenolide
      induced transient, reversible biological effect on marine medaka, while DCOIT
      could impair reproductive success of fish, as evident by clear alterations of the
      E2/T ratio. The relatively low toxicity of butenolide on marine biota highlights
      its promising application in the antifouling industry. The present findings also
      emphasize gender difference in fish susceptibility to chemical treatment
      (male>female), which is an important consideration for ecological risk
      assessment. 

PMID- 24583293
TI  - Circulating cardiac troponin T exhibits a diurnal rhythm.
AB  - OBJECTIVES: The goal of this study was to test the unverified assumption that
      chronically elevated cardiac troponin T (cTnT) levels fluctuate randomly around a
      homeostatic set point. BACKGROUND: The introduction of high-sensitivity cardiac
      troponin (cTn) assays has improved sensitivity for acute myocardial infarction
      (AMI). However, many patients with a single positive cTn test result do not have
      AMI. Therefore, the diagnosis of AMI relies strongly on serial testing and
      interpretation of cTn kinetics. Essential in this regard is a profound
      understanding of the biological variation of cTn. METHODS: Two studies were
      conducted to assess biological cTnT variation and to investigate the presence of
      a diurnal rhythm of cTnT. Study 1 comprised 23 male subjects with type 2
      diabetes, with no acute cardiovascular disease. Serial venous blood samples were
      drawn over an 11-h period (8:30 am to 7:30 pm). In study 2, the presence of a
      diurnal cTnT rhythm was investigated by hourly sampling of 7 subjects from study
      1 over 25 h. RESULTS: In study 1, we observed a gradual decrease in cTnT
      concentrations during the day (24 +/- 2%). This decrease was present in all
      participants and was most prominent in subjects with the highest baseline cTnT
      values (Pearson's R 0.93). Diurnal variation of cTnT, as assessed in study 2, was
      characterized by peak concentrations during morning hours (8:30 am, 17.1 +/- 2.9
      ng/l), gradually decreasing values during daytime (8:30 pm, 11.9 +/- 1.6 ng/l),
      and rising concentrations during nighttime (8:30 am the next day, 16.9 +/- 2.8
      ng/l). CONCLUSIONS: A diurnal cTnT rhythm substantiates the recommendation that
      all dynamic changes in cTnT should be interpreted in relation to the clinical
      presentation. Epidemiological studies and risk-stratification protocols with the
      use of cTnT may benefit from standardized sampling times. (Exercise and Glycemic
      Control in Type 2 Diabetes; NCT00945165).

PMID- 24583291
TI  - Primate phylogenetic relationships and divergence dates inferred from complete
      mitochondrial genomes.
AB  - The origins and the divergence times of the most basal lineages within primates
      have been difficult to resolve mainly due to the incomplete sampling of early
      fossil taxa. The main source of contention is related to the discordance between
      molecular and fossil estimates: while there are no crown primate fossils older
      than 56Ma, most molecule-based estimates extend the origins of crown primates
      into the Cretaceous. Here we present a comprehensive mitogenomic study of
      primates. We assembled 87 mammalian mitochondrial genomes, including 62 primate
      species representing all the families of the order. We newly sequenced eleven
      mitochondrial genomes, including eight Old World monkeys and three
      strepsirrhines. Phylogenetic analyses support a strong topology, confirming the
      monophyly for all the major primate clades. In contrast to previous mitogenomic
      studies, the positions of tarsiers and colugos relative to strepsirrhines and
      anthropoids are well resolved. In order to improve our understanding of how
      fossil calibrations affect age estimates within primates, we explore the effect
      of seventeen fossil calibrations across primates and other mammalian groups and
      we select a subset of calibrations to date our mitogenomic tree. The divergence
      date estimates of the Strepsirrhine/Haplorhine split support an origin of crown
      primates in the Late Cretaceous, at around 74Ma. This result supports a short
      fuse model of primate origins, whereby relatively little time passed between the
      origin of the order and the diversification of its major clades. It also suggests
      that the early primate fossil record is likely poorly sampled. 

PMID- 24583295
TI  - Incidence and causes of sudden death in U.S. college athletes.
AB  - OBJECTIVES: The goal of this study was to reliably define the incidence and
      causes of sudden death in college student-athletes. BACKGROUND: The frequency
      with which cardiovascular-related sudden death occurs in competitive athletes
      importantly influences considerations for pre-participation screening strategies.
      METHODS: We assessed databases (including autopsy reports) from both the U.S.
      National Registry of Sudden Death in Athletes and the National Collegiate
      Athletic Association (2002 to 2011). RESULTS: Over the 10-year study period, 182
      sudden deaths occurred (age 20 +/- 1.7 years; 85% male; 64% white), 52 resulting
      from suicide (n = 31) or drug abuse (n = 21) and 64 probably or likely
      attributable to cardiovascular causes (6/year). Of these 64 athletes, 47 had a
      confirmed post-mortem diagnosis; the most common were hypertrophic cardiomyopathy
      in 21 and congenital coronary anomalies in 8. The 4,052,369 athlete
      participations (in 30 sports over 10 years) incurred mortality risks as follows:
      suicide and drugs combined, 1.3/100,000 athlete participation-years (5
      deaths/year); and documented cardiovascular disease, 1.2/100,000 athlete
      participation-years (4 deaths/year). Notably, cardiovascular deaths were 5-fold
      more common in African-American athletes than in white athletes (3.8 vs.
      0.7/100,000 athlete participation-years; p < 0.01) but did not differ from the
      general population of the same age and race (p = 0.6). CONCLUSIONS: In college
      student-athletes, risk of sudden death due to cardiovascular disease is
      relatively low, with mortality rates similar to suicide and drug abuse, but less
      than expected in the general population, although highest in African-American
      athletes. A substantial minority of confirmed cardiovascular deaths would not
      likely have been reliably detected by pre-participation screening with 12-lead
      electrocardiograms.

PMID- 24583294
TI  - A randomized trial of deferred stenting versus immediate stenting to prevent no-
      or slow-reflow in acute ST-segment elevation myocardial infarction (DEFER-STEMI).
AB  - OBJECTIVES: The aim of this study was to assess whether deferred stenting might
      reduce no-reflow and salvage myocardium in primary percutaneous coronary
      intervention (PCI) for ST-segment elevation myocardial infarction (STEMI).
      BACKGROUND: No-reflow is associated with adverse outcomes in STEMI. METHODS: This
      was a prospective, single-center, randomized, controlled, proof-of-concept trial
      in reperfused STEMI patients with >=1 risk factors for no-reflow. Randomization
      was to deferred stenting with an intention-to-stent 4 to 16 h later or
      conventional treatment with immediate stenting. The primary outcome was the
      incidence of no-/slow-reflow (Thrombolysis In Myocardial Infarction <=2). Cardiac
      magnetic resonance imaging was performed 2 days and 6 months after myocardial
      infarction. Myocardial salvage was the final infarct size indexed to the initial
      area at risk. RESULTS: Of 411 STEMI patients (March 11, 2012 to November 21,
      2012), 101 patients (mean age, 60 years; 69% male) were randomized (52 to the
      deferred stenting group, 49 to the immediate stenting). The median (interquartile
      range [IQR]) time to the second procedure in the deferred stenting group was 9 h
      (IQR: 6 to 12 h). Fewer patients in the deferred stenting group had no-/slow
      reflow (14 [29%] vs. 3 [6%]; p = 0.006), no reflow (7 [14%] vs. 1 [2%]; p =
      0.052) and intraprocedural thrombotic events (16 [33%] vs. 5 [10%]; p = 0.010).
      Thrombolysis In Myocardial Infarction coronary flow grades at the end of PCI were
      higher in the deferred stenting group (p = 0.018). Recurrent STEMI occurred in 2
      patients in the deferred stenting group before the second procedure. Myocardial
      salvage index at 6 months was greater in the deferred stenting group (68 [IQR:
      54% to 82%] vs. 56 [IQR: 31% to 72%]; p = 0.031]. CONCLUSIONS: In high-risk STEMI
      patients, deferred stenting in primary PCI reduced no-reflow and increased
      myocardial salvage. (Deferred Stent Trial in STEMI; NCT01717573).

PMID- 24583296
TI  - Percutaneous approaches to valve repair for mitral regurgitation.
AB  - Percutaneous therapy has emerged as an option for treatment of mitral
      regurgitation for selected, predominantly high-risk patients. Most of the
      percutaneous approaches are modifications of existing surgical approaches.
      Catheter-based devices mimic these surgical approaches with less procedural risk,
      due to their less-invasive nature. Percutaneous annuloplasty can be achieved
      indirectly via the coronary sinus or directly from retrograde left ventricular
      access. Catheter-based leaflet repair with the MitraClip (Abbott Laboratories,
      Abbott Park, Illinois) is accomplished with an implantable clip to mimic the
      surgical edge-to-edge leaflet repair technique. A large experience with MitraClip
      has been reported, and several other percutaneous approaches have been
      successfully used in smaller numbers of patients to demonstrate proof of concept,
      whereas others have failed and are no longer under development. There is
      increasing experience in both trials and practice to begin to define the clinical
      utility of percutaneous leaflet repair, and annuloplasty approaches are
      undergoing significant development. Transcatheter mitral valve replacement is
      still in early development.

PMID- 24583297
TI  - Cardiac rhythm management devices: when regulatory agencies "over-regulate".

PMID- 24583298
TI  - Arterial stiffness mapping: a better navigation to Ithaca?

PMID- 24583299
TI  - Safety of computed tomography in patients with cardiac rhythm management devices:
      assessment of the U.S. Food and Drug Administration advisory in clinical
      practice.
AB  - OBJECTIVES: To assess the safety of computed tomography (CT) imaging in patients
      with cardiac rhythm management (CRM) devices, which was subject to an advisory
      from the U.S. Food and Drug Administration (FDA) in 2008. BACKGROUND: The FDA
      warned about potential interference of CT imaging with CRM devices and made
      recommendations for clinical practice despite only limited evidence. METHODS: All
      516 CT scans that involved direct radiation exposure of CRM devices (332
      defibrillators, 184 pacemakers) at 2 large-volume centers between July 2000 and
      May 2010 were included. The primary outcome was a composite endpoint of death,
      bradycardia or tachycardia requiring termination of the scan or an immediate
      intervention, unplanned hospital admission, reprogramming of the device,
      inappropriate defibrillator shocks, or device replacement/revision thought to be
      due to CT imaging. Significant changes in device parameters were sought as a
      secondary outcome (control group 4:1 ratio). RESULTS: The main finding was that
      none of the CTs were associated with the primary outcome. With serial device
      interrogations, there were no differences in changes in battery voltage or lead
      parameters between devices exposed to radiation and their controls. Potentially
      significant changes in device parameters were observed in a small group of
      devices (both the CT group and control group), but no definitive link to CT was
      confirmed, and there were no associated clinical consequences. CONCLUSIONS: The
      findings suggest that the presence of CRM devices should not delay or result in
      cancellation of clinically indicated CT imaging procedures, and provide evidence
      that would be helpful when the FDA advisory is re-evaluated.

PMID- 24583300
TI  - Prevalence of electrocardiographic anomalies in young individuals: relevance to a
      nationwide cardiac screening program.
AB  - OBJECTIVES: This study sought to investigate the prevalence of potentially
      abnormal electrocardiographic (ECG) patterns in young individuals to assess the
      implications for a nationwide screening program for conditions causing sudden
      cardiac death (SCD). BACKGROUND: The Italian experience suggests that pre
      participation screening with ECG reduces the incidence of SCD in athletes.
      However, the majority of SCDs occur in nonathletes. In the United Kingdom,
      screening for cardiac disorders is confined to symptomatic individuals or those
      with a family history of inherited cardiac conditions or premature cardiac death.
      METHODS: Between 2008 and 2012, 7,764 nonathletes ages 14 to 35 years underwent
      ECG screening. Electrocardiograms were analyzed for group 1 (training-related)
      and group 2 (potentially pathological) patterns presented in the 2010 European
      Society of Cardiology position paper, which advocates further evaluation for
      individuals with group 2 ECG patterns. Results were compared with 4,081 athletes.
      RESULTS: Group 1 patterns occurred in 49.1% of nonathletes and 87.4% of athletes
      (p < 0.001). Group 2 patterns occurred in 21.8% of nonathletes and 33% of
      athletes (p < 0.001). In nonathletes, QTc interval abnormalities comprised the
      majority (52%) of group 2 changes, whereas T-wave inversions constituted 11%.
      Male sex and African/Afro-Caribbean ethnicity demonstrated the strongest
      association with group 2 ECG patterns. CONCLUSIONS: The study demonstrates that 1
      in 5 young people have group 2 ECG patterns. The low incidence of SCD in young
      people suggests that in most instances such patterns are non-specific. These
      findings have significant implications on the feasibility and cost-effectiveness
      of nationwide screening programs for cardiovascular disease in young nonathletes
      and athletes alike, on the basis of current guidelines.

PMID- 24583301
TI  - ECG screening is not warranted for the recreational athlete.

PMID- 24583302
TI  - As REGARDS treatment goal attainment compared with COURAGE: the perfect should
      not be the enemy of the good.

PMID- 24583303
TI  - Allen or no Allen: that is the question!

PMID- 24583305
TI  - Transradial coronary catheterization and intervention across the whole spectrum
      of Allen test results.
AB  - OBJECTIVES: The aim of this study was to investigate the safety and feasibility
      of transradial coronary catheterization across the whole spectrum of Allen test
      (AT) results. BACKGROUND: Whether the AT can predict ischemic complications after
      transradial access (TRA) is controversial. No prospective assessment exists on
      the safety and feasibility of TRA across the whole spectrum of AT results.
      METHODS: From October 2007 to June 2009, a total of 942 patients undergoing TRA
      were screened, and 203 were recruited, of whom 83, 60, and 60 had normal,
      intermediate, and abnormal AT results, respectively. Patients underwent serial
      assessments of thumb capillary lactate (the primary endpoint), thumb
      plethysmography, and ulnar frame count to investigate the patency of the
      ulnopalmar arches, as well as handgrip strength tests to examine the isometric
      strength of the hand and forearm muscles and discomfort ratings. RESULTS: Lactate
      did not differ among the 3 study groups after the procedure (1.85 +/- 0.93 mmol/l
      in patients with normal AT results, 1.85 +/- 0.66 mmol/l in those with
      intermediate results, and 1.97 +/- 0.71 mmol/l in those with abnormal results; p
      = 0.59) or at other time points during the study. Plethysmographic readings
      showed improvements of ulnopalmar collateralization in patients with non-normal
      AT results, whereas the ulnar frame count was decreased, suggesting enhanced
      ulnar flow, in patients with abnormal AT results after TRA. Handgrip strength
      test results and discomfort ratings did not differ across AT groups. No hand
      ischemic complications occurred. CONCLUSIONS: This study provides proof of
      concept for a paradigm shift in cardiovascular intervention, suggesting the
      safety and feasibility of TRA across the whole spectrum of AT results. Given the
      multiple implications of our findings, a broader clinical validation is needed.
      (Predictive Value of Allen's Test Result in Elective Patients Undergoing Coronary
      Catheterization Through Radial Approach [RADAR]; NCT00597324).

PMID- 24583304
TI  - Myocardial bridging: contemporary understanding of pathophysiology with
      implications for diagnostic and therapeutic strategies.
AB  - Patients with myocardial bridging are often asymptomatic, but this anomaly may be
      associated with exertional angina, acute coronary syndromes, cardiac arrhythmias,
      syncope, or even sudden cardiac death. This review presents our understanding of
      the pathophysiology of myocardial bridging and describes prevailing diagnostic
      modalities and therapeutic options for this challenging clinical entity.

PMID- 24583306
TI  - Local stiffness of the carotid and femoral artery is associated with incident
      cardiovascular events and all-cause mortality: the Hoorn study.
AB  - OBJECTIVES: This study sought to investigate the association of local and
      segmental arterial stiffness with incident cardiovascular events and all-cause
      mortality. BACKGROUND: The association of different stiffness indices, in
      particular of carotid, brachial, and femoral stiffness, with cardiovascular
      disease and mortality is currently unknown. METHODS: In a population-based cohort
      (n = 579, mean age 67 years, 50% women, 23% with type 2 diabetes [by design]), we
      assessed local stiffness of carotid, femoral, and brachial arteries (by
      ultrasonography), carotid-femoral pulse wave velocity (cfPWV), aortic
      augmentation index, and systemic arterial compliance. RESULTS: After a median
      follow-up of 7.6 years, 130 participants had a cardiovascular event and 96 had
      died. The hazard ratios (HRs) (95% confidence intervals [CIs]) per 1 SD for
      cardiovascular events and all-cause mortality, respectively, were HR: 1.22 (95%
      CI: 0.95 to 1.56) and 1.51 (95% CI: 1.11 to 2.06) for lower carotid
      distensibility; HR: 1.19 (95% CI: 1.00 to 1.41) and 1.28 (95% CI: 1.07 to 1.53)
      for higher carotid elastic modulus; HR: 1.08 (95% CI: 0.88 to 1.31) and 1.43 (95%
      CI: 1.10 to 1.86) for lower carotid compliance; HR: 1.39 (95% CI: 1.06 to 1.83)
      and 1.27 (95% CI: 0.90 to 1.79) for lower femoral distensibility; HR: 1.25 (95%
      CI: 0.96 to 1.63) and 1.47 (95% CI: 1.01 to 2.13) for lower femoral compliance;
      and HR: 1.56 (95% CI: 1.23 to 1.98) and 1.13 (95% CI: 0.83 to 1.54) for higher
      cfPWV. These results were adjusted for age, sex, mean arterial pressure, and
      cardiovascular risk factors. Mutual adjustments for each of the other stiffness
      indices did not materially change these results. Brachial stiffness, augmentation
      index, and systemic arterial compliance were not associated with cardiovascular
      events or mortality. CONCLUSIONS: Carotid and femoral stiffness indices are
      independently associated with incident cardiovascular events and all-cause
      mortality. The strength of these associations with events may differ per
      stiffness parameter.

PMID- 24583307
TI  - Real-time 3-dimensional transesophageal echocardiography in the assessment of
      ventriculoatrial shunt (Gerbode defect) complicating simultaneous mitral and
      tricuspid valve repair.

PMID- 24583308
TI  - Left main coronary artery protection during transcatheter aortic valve
      deployment.

PMID- 24583309
TI  - microRNAs in cardiovascular diseases: current knowledge and the road ahead.
AB  - Over the last few years, the field of microribonucleic acid (miRNA) in
      cardiovascular biology and disease has expanded at an incredible pace. miRNAs are
      themselves part of a larger family, that of non-coding RNAs, the importance of
      which for biological processes is starting to emerge. miRNAs are ~22-nucleotide
      long RNA sequences that can legate messenger (m)RNAs at partially complementary
      binding sites, and hence regulate the rate of protein synthesis by altering the
      stability of the targeted mRNAs. In the cardiovascular system, miRNAs have been
      shown to be critical regulators of development and physiology. They control basic
      functions in virtually all cell types relevant to the cardiovascular system (such
      as endothelial cells, cardiac muscle, smooth muscle, inflammatory cells, and
      fibroblasts) and, thus, are directly involved in the pathophysiology of many
      cardiovascular diseases. As a result of their role in disease, they are being
      studied for exploitation in diagnostics, prognostics, and therapeutics. However,
      there are still significant obstacles that need to be overcome before they enter
      the clinical arena. We present here a review of the literature and outline the
      directions toward their use in the clinic.

PMID- 24583310
TI  - Dilated cardiomyopathy with inferior wall myocardial infarction: a rare
      presentation of Takayasu arteritis.

PMID- 24583311
TI  - Advances in the understanding of plaque composition and treatment options: year
      in review.
AB  - Atherosclerosis research has classically followed 2 intertwining lines of
      investigation concerning atherosclerosis as a local process (the "high-risk
      plaque") and as a systemic disease (the "high-risk patient"). Over time, the
      weight of attention has swung, like a pendulum, between these 2 related foci.
      With optimal medical therapy and attention to risk factors firmly established as
      fundamental aspects of management, in the past year, we have nevertheless
      perceived a shift in the pendulum toward renewed focus on the local plaque. We
      contend that this shift results from a convergence of major advances in
      understanding the biology of plaque progression, novel sophisticated invasive and
      noninvasive imaging modalities for the in vivo characterization of plaque
      composition and inflammation, and emerging data and technologies that have
      renewed interest in locally targeted interventions. Here, we review the dynamic
      and exciting progress that has occurred over the last 12 months in this arena,
      while acknowledging future work that remains to be done to refine and validate
      new imaging modalities and therapies.

PMID- 24583312
TI  - Molecular modeling and molecular dynamics simulations of GPI 14 in Leishmania
      major: insight into the catalytic site for active site directed drug design.
AB  - Leishmania major causes cutaneous form of Leishmaniasis affecting 21 million
      people in developing countries. Overuse of the chemotherapeutics against
      leishmaniasis has resulted in the development of drug resistance in the parasite.
      To surmount this emerging threat we have attempted to target the surface
      molecules. Glycosylphosphatidylinositol is one such molecule that is present
      abundantly and thus our work revolves around the enzyme mannosyltransferase (GPI
      14), an enzyme essential to add mannose on the glycosylphosphatidyl. It has been
      targeted for drug discovery on account of growing resistance to miltefosine in L.
      major. This paper serves as the first attempt to detect GPI 14 gene in L. major
      supported with modeling and molecular dynamic analysis of complete three
      dimensional structure of GPI 14. The functional analysis revealed multiple
      transmembrane regions in GPI 14 and a close phylogenetic relation with
      Trypanosoma species and Schistosoma mansoni with highest bootstrap values. The
      protein model obtained was subjected to minimization for 14ns simulation. Eight
      derivatives of N-4-(-5(trifluromethyl)-1-methyl-1H benzo[d]imidazole-2 yl)
      phenyl) were docked onto GPI 14. The contact frequency of GPI 14 with the docked
      compounds suggested the inhibition of mannosylation proposing the druggability
      for leishmaniasis therapy. 

PMID- 24583313
TI  - The diabetic vasculature: physiological mechanisms of dysfunction and influence
      of aerobic exercise training in animal models.
AB  - Diabetes mellitus (DM) is associated with a number of complications of which
      chronic vascular complications are undoubtedly the most complex and significant
      consequence. With a significant impact on health care, 50-80% of people with
      diabetes die of cardiovascular disease (including coronary artery disease,
      stroke, peripheral vascular disease and other vascular disease), making it the
      major cause of morbidity and mortality in diabetic patients. A healthy lifestyle
      is essential in the management of DM, especially the inclusion of aerobic
      exercise, which has been shown effective in reducing the deleterious effects in
      vasculature. Interest in exercise studies has increased significantly with
      promising results that demonstrate a future for investigation. Considering the
      importance of this emerging field, the aim of this mini-review is to summarize
      and integrate animal studies investigating physiological mechanisms of vascular
      dysfunction and remodeling in type 1 diabetes mellitus (T1DM) and type 2 diabetes
      mellitus (T2DM) and how these are influenced by chronic aerobic exercise
      training. 

PMID- 24583315
TI  - Massage therapy restores peripheral vascular function after exertion.
AB  - OBJECTIVE: To determine if lower extremity exercise-induced muscle injury reduces
      vascular endothelial function of the upper extremity and if massage therapy (MT)
      improves peripheral vascular function after exertion-induced muscle injury.
      DESIGN: Randomized, blinded trial with evaluations at 90 minutes, 24 hours, 48
      hours, and 72 hours. SETTING: Clinical research center. PARTICIPANTS: Sedentary
      young adults (N=36) were randomly assigned to 1 of 3 groups: (1) exertion-induced
      muscle injury and MT (n=15; mean age +/- SE, 26.6 +/- 0.3); (2) exertion-induced
      muscle injury only (n=10; mean age +/- SE, 23.6 +/- 0.4), and (3) MT only (n=11;
      mean age +/- SE, 25.5 +/- 0.4). INTERVENTION: Participants were assigned to
      exertion-induced muscle injury only (a single bout of bilateral, eccentric leg
      press exercise), MT only (30-min lower extremity massage using Swedish
      technique), or exertion-induced muscle injury and MT. MAIN OUTCOME MEASURES:
      Brachial artery flow-mediated dilation (FMD) was determined by ultrasound at each
      time point. Nitroglycerin (NTG)-induced dilation was also assessed (0.4 mg).
      RESULTS: Brachial FMD increased from baseline in the exertion-induced muscle
      injury and MT group and the MT only group (7.38%+/-.18% to 9.02%+/-.28%, P<.05
      and 7.77%+/-.25% to 10.2%+/-.22%, P<.05, respectively) at 90 minutes and remained
      elevated until 72 hours. In the exertion-induced muscle injury only group, FMD
      was reduced from baseline at 24 and 48 hours (7.78%+/-.14% to 6.75%+/-.11%, P<.05
      and 6.53%+/-.11%, P<.05, respectively) and returned to baseline after 72 hours.
      Dilations of NTG were similar over time. CONCLUSIONS: Our results suggest that MT
      attenuates impairment of upper extremity endothelial function resulting from
      lower extremity exertion-induced muscle injury in sedentary young adults.

PMID- 24583317
TI  - Highly sensitive and rapid bacteria detection using molecular beacon-Au
      nanoparticles hybrid nanoprobes.
AB  - Since many diseases are caused by pathogenic bacterial infections, accurate and
      rapid detection of pathogenic bacteria is in urgent need to timely apply
      appropriate treatments and to reduce economic costs. To end this, we designed
      molecular beacon-Au nanoparticle hybrid nanoprobes to improve the bacterial
      detection efficiency and sensitivity. Here, we show that the designed molecular
      beacon modified Au nanoparticles could specifically recognize synthetic DNAs
      targets and can readily detect targets in clinical samples. Moreover, the hybrid
      nanoprobes can recognize Escherichia coli within an hour at a concentration of
      10(2) cfu/ml, which is 1000-folds sensitive than using molecular beacon directly.
      Our results show that the molecular beacon-Au nanoparticle hybrid nanoprobes have
      great potential in medical and biological applications.

PMID- 24583316
TI  - Sensitive detection of Ochratoxin A in food and drinks using metal-enhanced
      fluorescence.
AB  - Easy, sensitive, rapid and low cost ochratoxin biosensors are strongly demanded
      in food analysis since Ochratoxin A (OTA) is a widely diffused food contaminant,
      highly detrimental for human health. In this work, a novel plasmonic based
      optical biosensor prototype for ochratoxin A is described. It exploits the metal
      enhanced fluorescence phenomenon due to the silver film over nanosphere plasmonic
      substrate. Since ochratoxin A could be present in different food commodities,
      sensor performances have been tested on three different matrices (dried milk,
      juices, and wheat mix). Firstly, a common OTA extraction solvent and a labeling
      and detection protocol were defined for the analyzed matrices. Then, the
      efficiency of the Ag-FON surfaces in signal amplification for the detection of
      low ochratoxin A concentrations was defined. Using samples spiked with OTA-AF 647
      or with unlabeled OTA we were able to detect the mycotoxin at concentrations
      lower than E.U. specifications of 0.5 MUg/kg in wheat, milk and apple juice. The
      test performances are comparable to those of ELISA kits but the platform
      presented here, once optimized, present some perspective advantages, such as: low
      cost and time consuming, versatility of the protocol for the investigation of
      different matrices, employment also in non-qualified laboratories, small
      dimensions that allow its integration in a compact device for OTA on-site
      detection.

PMID- 24583314
TI  - c-Cbl inhibition improves cardiac function and survival in response to myocardial
      ischemia.
AB  - BACKGROUND: The proto-oncogene Casitas b-lineage lymphoma (c-Cbl) is an adaptor
      protein with an intrinsic E3 ubiquitin ligase activity that targets receptor and
      nonreceptor tyrosine kinases, resulting in their ubiquitination and
      downregulation. However, the function of c-Cbl in the control of cardiac function
      is currently unknown. In this study, we examined the role of c-Cbl in myocyte
      death and cardiac function after myocardial ischemia. METHODS AND RESULTS: We
      show increased c-Cbl expression in human ischemic and dilated cardiomyopathy
      hearts and in response to pathological stress stimuli in mice. c-Cbl-deficient
      mice demonstrated a more robust functional recovery after myocardial
      ischemia/reperfusion injury and significantly reduced myocyte apoptosis and
      improved cardiac function. Ubiquitination and downregulation of key survival c
      Cbl targets, epidermal growth factor receptors and focal adhesion kinase, were
      significantly reduced in c-Cbl knockout mice. Inhibition of c-Cbl expression or
      its ubiquitin ligase activity in cardiac myocytes offered protection against H2O2
      stress. Interestingly, c-Cbl deletion reduced the risk of death and increased
      cardiac functional recovery after chronic myocardial ischemia. This beneficial
      effect of c-Cbl deletion was associated with enhanced neoangiogenesis and
      increased expression of vascular endothelial growth factor-a and vascular
      endothelial growth factor receptor type 2 in the infarcted region. CONCLUSIONS: c
      Cbl activation promotes myocyte apoptosis, inhibits angiogenesis, and causes
      adverse cardiac remodeling after myocardial infarction. These findings point to c
      Cbl as a potential therapeutic target for the maintenance of cardiac function and
      remodeling after myocardial ischemia.

PMID- 24583318
TI  - Facile colorimetric detection of Hg2+ based on anti-aggregation of silver
      nanoparticles.
AB  - This paper describes an investigation of a facile colorimetric sensor for Hg(2+)
      in aqueous solution based on the anti-aggregation of silver nanoparticles
      (AgNPs). In the absence of Hg(2+), the addition of 6-Thioguanine to AgNPs
      solution led to the aggregation of AgNPs, resulting in a color change from yellow
      to brown with a red shift of absorption spectra. However, the presence of Hg(2+)
      inhibited the 6-Thioguanine-induced aggregation of AgNPs accompanying with a
      color change from brown to yellow. Under the optimal conditions, the ratio
      between the absorbance at 530 nm and 394 nm (A530/A394) was linearly proportional
      to the Hg(2+) concentration in a range from 0 to 333 nM with a detection limit of
      4 nM. Other environmentally relevant metal ions did not interfere with the
      detection of Hg(2+). The proposed method was simple, cost-effective and rapid
      without any complicated modifying step. It was successfully applied to detect
      Hg(2+) in environmental water samples.

PMID- 24583319
TI  - Drug treatment of epilepsy in adults.
AB  - Epilepsy is a serious, potentially life shortening brain disorder, the symptoms
      of which can be successfully treated in most patients with one or more
      antiepileptic drug. About two in three adults with new onset epilepsy will
      achieve lasting seizure remission on or off these drugs, although around half
      will experience mild to moderately severe adverse effects. Patients with
      epilepsy, especially the 20-30% whose seizures are not fully controlled with
      available drugs (drug resistant epilepsy), have a significantly increased risk of
      death, as well as psychiatric and somatic comorbidities, and adverse effects from
      antiepileptic drugs. Newer drugs have brought more treatment options, and some
      such as levetiracetam cause fewer drug interactions and less hypersensitivity
      than older ones. However, they do not reduce the prevalence of drug resistant
      epilepsy or prevent the development of epilepsy in patients at high risk, such as
      those with a traumatic brain injury. The development of antiepileptic drugs
      urgently needs to be revitalized so that we can discover more effective
      antiseizure drugs for the treatment of drug resistant epilepsy, including
      catastrophic forms. Antiepileptogenic agents to prevent epilepsy before the first
      seizure in at risk patients and disease modifying agents to control ongoing
      severe epilepsy associated with progressive underlying disease are also needed. 

PMID- 24583320
TI  - Evaluation of antibacterial and remineralizing nanocomposite and adhesive in rat
      tooth cavity model.
AB  - Antibacterial and remineralizing dental composites and adhesives were recently
      developed to inhibit biofilm acids and combat secondary caries. It is not clear
      what effect these materials will have on dental pulps in vivo. The objectives of
      this study were to investigate the antibacterial and remineralizing restorations
      in a rat tooth cavity model, and determine pulpal inflammatory response and
      tertiary dentin formation. Nanoparticles of amorphous calcium phosphate (NACP)
      and antibacterial dimethylaminododecyl methacrylate (DMADDM) were synthesized and
      incorporated into a composite and an adhesive. Occlusal cavities were prepared in
      the first molars of rats and restored with four types of restoration: control
      composite and adhesive; control plus DMADDM; control plus NACP; and control plus
      both DMADDM and NACP. At 8 or 30days, rat molars were harvested for histological
      analysis. For inflammatory cell response, regardless of time periods, the NACP
      group and the DMADDM+NACP group showed lower scores (better biocompatibility)
      than the control group (p=0.014 for 8days, p=0.018 for 30days). For tissue
      disorganization, NACP and DMADDM+NACP had better scores than the control
      (p=0.027) at 30days. At 8days, restorations containing NACP had a tertiary dentin
      thickness (TDT) that was five- to six-fold that of the control. At 30days,
      restorations containing NACP had a TDT that was four- to six-fold that of the
      control. In conclusion, novel antibacterial and remineralizing restorations were
      tested in rat teeth in vivo for the first time. Composite and adhesive containing
      NACP and DMADDM exhibited milder pulpal inflammation and much greater tertiary
      dentin formation than the control adhesive and composite. Therefore, the novel
      composite and adhesive containing NACP and DMADDM are promising as a new
      therapeutic restorative system to not only combat oral pathogens and biofilm
      acids as shown previously, but also facilitate the healing of the dentin-pulp
      complex.

PMID- 24583321
TI  - Association of calpastatin gene polymorphisms and meat quality traits in pig.
AB  - Calpastatin is associated with the rate of post mortem degradation of structural
      proteins due to the regulation of calpain activity. In the present research, the
      associations between polymorphisms within 6th intron of porcine CAST gene and
      several meat quality traits were analyzed. The CAST gene polymorphisms affected
      meat colour, pH, water holding-capacity (WHC) and texture parameters (toughness,
      firmness, cohesiveness, chewiness, and resilience) measured in longissimus dorsi
      and semimembranosus muscles. The analysis performed on the most numerous breeds
      maintained in Poland, suggested that the most interesting polymorphisms were
      CAST/HpaII and CAST/RsaI, which had the greatest effect on WHC regardless of the
      breed analyzed and had an effect on meat pH, firmness and toughness for most
      breeds. Interestingly, for almost all breeds, the significant effect of both
      mutations on intramuscular fat content (IMF) was detected. The provided data
      confirmed the use of CAST gene as a genetic marker in breeding programmes which
      allows performing a selection focussed on improving the quality of pork. 

PMID- 24583322
TI  - Irradiated vacuum-packed lamb meat stored under refrigeration: microbiology,
      physicochemical stability and sensory acceptance.
AB  - Reducing spoilage and indicator bacteria is important for microbiological
      stability in meat and meat products. The objective was to evaluate the effect of
      different doses of gamma radiation on the shelf-life of lamb meat, vacuum-packed
      and stored under refrigeration, by assessing the microbiological safety,
      physicochemical stability and sensory quality. Lamb loin cuts (Longissimus dorsi)
      were irradiated with 1.5kGy and 3.0kGy. The samples, including control, were
      stored at 1+/-1 degrees C during 56days. Samples were analyzed on zero, 14, 28,
      42 and 56days by their microbiological and physicochemical characteristics.
      Sensory quality was carried out on day zero. The results showed a reduction
      (p<0.05) in the microbial load of the irradiated samples. The acceptance of lamb
      loins was not affected (p>0.05) by the radiation doses. Thus gamma irradiation at
      3.0kGy was effective in reducing the content of microorganisms, without harming
      the physicochemical characteristics evaluated. 

PMID- 24583323
TI  - Effects of linseed and quercetin added to the diet of fattening lambs on the
      fatty acid profile and lipid antioxidant status of meat samples.
AB  - Thirty-two Merino lambs fed barley straw and a concentrate formulated either with
      palm oil (CTRL group) or with linseed (+LS group), both alone or supplemented
      with quercetin (+QCT group or +LS+QCT group) were used to assess the effects of
      these dietary supplements on meat quality attributes. After being slaughtered,
      the longissimus thoracis muscles were used to study the fatty acid (FA) profile
      in detail, whilst longissimus lumborum slices were stored under refrigerated
      conditions to determine the lipid stability. Linseed increased the content of
      highly unsaturated n-3 long-chain fatty acid (20:5n-3; 22:5n-3; 22:6n-3).
      Interestingly, a significant increment of rumenic acid content (9c,11t-18:2) was
      observed when this seed was administered together with dietary quercetin.
      Moreover, the feeding of quercetin resulted in a reduction in the proportion of
      saturated FA and a decrease in lipid peroxidation of meat when the lambs were fed
      linseed. In conclusion, from both a nutritional and a commercial (shelf-life)
      point of view, it may be useful to include a source of quercetin when lambs are
      fed linseed diets. 

PMID- 24583324
TI  - Evaluation of mortadella formulated with carbon monoxide-treated porcine blood.
AB  - The proximate composition and color of mortadellas containing carbon monoxide
      treated (COTB), untreated (UNTB), or CO-treated dried blood (CODB) were compared
      to that of control mortadella. Blood addition did not affect (P>0.05) the
      proximate composition and TBARS. The mortadella containing 10% UNTB were brown
      and those containing COTB or CODB were red. Residual nitrite level, L*, a*, b*
      and c* values of the mortadella decreased (P<0.05) with an increase in the amount
      of blood; TBARs did not vary (P>0.05). Increasing the amount of blood increased
      (P<0.05) the hue angle (h*) and browning index (BI) of the mortadella containing
      UNTB. Increasing blood addition decreased (P<0.05) h* and did not affect (P>0.05)
      BI. Increasing storage length decreased (P<0.05) residual nitrite, affected BI
      and color coordinates and did not affect TBARS (P>0.05). Addition of CO-treated
      blood allows the production of better-colored sausages having lower residual
      nitrite levels. 

PMID- 24583325
TI  - Antioxidant properties of extracts from Ginkgo biloba leaves in meatballs.
AB  - The aim was to determine the effect of Ginkgo leaf extracts on the stability of
      lipids and cholesterol in pork meatballs over 21days of refrigerated storage. The
      antioxidants used were characterized by their antioxidant activity towards lipids
      and cholesterol. Extracts were prepared from green and yellow leaves from Ginkgo
      biloba L. trees. Water, acetone and ethanol were used as extractants. The
      extracts showed stabilizing effects on both lipid and cholesterol oxidation
      processes. The lipid oxidation process of pork meatballs was mostly inhibited by
      the aqueous and ethanolic extracts of the yellow leaves. Their antioxidant
      activity was higher than that of BHT. All the extracts had a stabilizing effect
      on cholesterol and most of them inhibited the formation of oxidized derivatives.
      The acetone and ethanol extracts of green leaves and the ethanol extract of
      yellow leaves inhibited the formation of cholesterol oxidation products formation
      most effectively. 

PMID- 24583326
TI  - The effect of protein oxidation on hydration and water-binding in pork packaged
      in an oxygen-enriched atmosphere.
AB  - This study investigated the in situ oxidative process of myofibrillar proteins in
      boneless pork loin chops (Longissimus lumborum) packaged in an oxygen-enriched
      atmosphere (HiOx: 80% O2/20% CO2), an air-permeable polyvinylchloride (PVC)
      overwrap, or a partial vacuum (VP) throughout display at 2 degrees C for up to
      14, 7, and 21days, respectively. Samples stored in HiOx were susceptible to lipid
      (TBARS) and protein (carbonyls, sulfhydryls, and aggregation) oxidation, while
      samples in PVC and VP showed lesser oxidative changes. Water-holding capacity of
      raw muscle decreased (P<0.05) when stored in HiOx but not in PVC and VP. Upon
      salt and phosphate brine marination, HiOx and PVC muscle samples had improved
      hydration capacity during display compared with non-stored control, but display
      generally decreased hydration of VP samples. The result was in agreement with
      myofibril structural changes. Despite the enhanced hydration, HiOx muscle was
      least capable of withholding moisture upon cooking. 

PMID- 24583327
TI  - Potential mechanisms of carbon monoxide and high oxygen packaging in maintaining
      color stability of different bovine muscles.
AB  - The objectives were to compare the effects of packaging methods on color
      stability, metmyoglobin-reducing-activity (MRA), total-reducing-activity and NADH
      concentration of different bovine muscles and to explore potential mechanisms in
      the enhanced color stability by carbon monoxide modified atmosphere packaging (CO
      MAP, 0.4% CO/30% CO2/69.6% N2). Steaks from longissimus lumborum (LL), psoas
      major (PM) and longissimus thoracis (LT) packaged in CO-MAP, high-oxygen modified
      atmosphere packaging (HiOx-MAP, 80% O2/20% CO2) or vacuum packaging were stored
      for 0day, 4days, 9days, and 14days or stored for 9days then displayed in air for
      0day, 1day, or 3days. The CO-MAP significantly increased red color stability of
      all muscles, and especially for PM. The PM and LT were more red than LL in CO
      MAP, whereas PM had lowest redness in HiOx-MAP. The content of MetMb in CO-MAP
      was lower than in HiOx-MAP. Steaks in CO-MAP maintained a higher MRA compared
      with those in HiOx-MAP during storage. After opening packages, the red color of
      steaks in CO-MAP deteriorated more slowly compared with that of steaks in HiOx
      MAP. 

PMID- 24583328
TI  - Functionality of liquid smoke as an all-natural antimicrobial in food
      preservation.
AB  - The smoking of foods, especially meats, has been used as a preservation technique
      for centuries. Today, smoking methods often involve the use of wood smoke
      condensates, commonly known as liquid smoke. Liquid smoke is produced by
      condensing wood smoke created by the pyrolysis of sawdust or wood chips followed
      by removal of the carcinogenic polyaromatic hydrocarbons. The main products of
      wood pyrolysis are phenols, carbonyls and organic acids which are responsible for
      the flavor, color and antimicrobial properties of liquid smoke. Several common
      food-borne pathogens such as Listeria monocytogenes, Salmonella, pathogenic
      Escherichia coli and Staphylococcus have shown sensitivity to liquid smoke in
      vitro and in food systems. Therefore liquid smoke has potential for use as an all
      natural antimicrobial in commercial applications where smoke flavor is desired.
      This review will cover the application and effectiveness of liquid smoke and
      fractions of liquid smoke as an all-natural food preservative. This review will
      be valuable for the industrial and research communities in the food science and
      technology areas. 

PMID- 24583329
TI  - European consumer attitudes on the associated health benefits of neutraceutical
      containing processed meats using Co-enzyme Q10 as a sample functional ingredient.
AB  - This study accumulated European consumer attitudes towards processed meats and
      their use as a functional food. A survey was set up using an online web
      application to gather information on consumer perception of processed meats as
      well as neutraceutical-containing processed meats. 548 responses were obtained
      and statistical analysis was carried out using a statistical software package.
      Data was summarized as frequencies for each question and statistical differences
      analyzed using the Chi-Square statistical test with a significance level of 5%
      (P<0.05). The majority of consumer attitudes towards processed meat indicate that
      they are unhealthy products. Most believe that processed meats contain large
      quantities of harmful chemicals, fat and salt. Consumers were found to be very
      pro-bioactive compounds in yogurt style products but unsure of their feelings in
      meat based products, which is likely due to the lack of familiarity to these
      products. Many of the respondents were willing to consume meat based functional
      foods but were not willing to pay more for them. 

PMID- 24583330
TI  - A false positive case due to matrix interference in the analysis of ronidazole
      residues in muscle tissue using LC-MS/MS.
AB  - In contrast with the information of the inspection body concerning the use of
      ronidazole, several non compliant muscle samples were detected using a liquid
      chromatography-tandem mass spectrometry (LC-MS/MS) method in accordance with
      confirmation criteria of Decision 2002/657/EC. This led to the suspicion that non
      compliance could be due to false positive results. In this context, a liquid
      chromatography-high resolution mass spectrometry (LC-HRMS) method was developed
      and sample extracts were re-analyzed, resolving the co eluting isobaric
      interfering peak, which also has an interfering product ion with the transition
      product (m/z 201>140). 

PMID- 24583331
TI  - Small heat shock protein degradation could be an indicator of the extent of
      myofibrillar protein degradation.
AB  - The objective of the present study was to evaluate the relationship between small
      heat shock proteins (sHSP) degradation and tenderness development of beef loins
      at different ultimate pH (pHu). A total of twelve loins (M. longissimus dorsi)
      from steers were obtained at 1 day post mortem. Shear force and proteolysis of
      each loin were analyzed at 1 and 28 days post mortem. The loins at intermediate
      pHu (5.8 to 6.0) showed more variation in tenderness compared to the loins at low
      pHu (<5.8), where few samples were still tough (>10kgF) at 28days. The intact
      sHSP20 was more pronounced (P<0.05) in the intermediate pHu loin compared to the
      low pHu counterpart. Further, high correlations between the degradation of both
      sHSP and myofibrillar proteins were observed (e.g. r=0.94; degraded sHSP27 and
      degraded desmin). The result of this study suggests that the extent of sHSP
      degradation could be an indicator of myofibrillar protein degradation and
      tenderness.

PMID- 24583332
TI  - Effect of different cooking methods on lipid oxidation and formation of volatile
      compounds in foal meat.
AB  - The influence of four different cooking methods (roasting, grilling, microwaving
      and frying) on cooking loss, lipid oxidation and volatile profile of foal meat
      was studied. Cooking loss were significantly (P<0.001) affected by thermal
      treatment, being higher (32.5%) after microwaving and lower after grilling
      (22.5%) and frying (23.8%). As expected, all the cooking methods increased TBARs
      content, since high temperature during cooking causes increased oxidation in foal
      steaks, this increase was significantly (P<0.001) higher when foal steaks were
      microwaved or roasted. The four different cooking methods led to increased total
      volatile compounds (between 366.7 and 633.1AU*10(6)/g dry matter) compared to raw
      steaks (216.4AU*10(6)/g dry matter). The roasted steaks showed the highest
      volatile content, indicating that increased cooking temperature increases the
      formation of volatile compounds. Aldehydes were the most abundant compounds in
      cooked samples, with amounts of 217.2, 364.5, 283.5 and 409.1AU*10(6)/g dry
      matter in grilled, microwaved, fried and roasted samples, respectively, whereas
      esters were the most abundant compounds in raw samples, with mean amounts of
      98.8AU*10(6)/g dry matter. 

PMID- 24583333
TI  - Dietary citrus pulp improves protein stability in lamb meat stored under aerobic
      conditions.
AB  - The antioxidant effects of dried citrus pulp on proteins in lamb meat, when used
      as a replacement of concentrate in the feed, was studied using meat from 26 male
      Comisana lambs. The lambs of age 90 days had been grouped randomly to receive one
      of the three dietary treatments: (1) commercial concentrate with 60% barley
      (Control, n=8), (2) concentrate with 35% barley and 24% citrus pulp (Cp24, n=9),
      or (3) concentrate with 23% barley and 35% citrus pulp (Cp35, n=9). Slices from
      the longissimus thoracis et lomborum muscle were packed aerobically and stored
      for up to 6days at 4 degrees C in the dark. The citrus pulp groups, Cp24 and
      Cp35, significantly decreased protein radicals and carbonyls, and preserved more
      thiols within six days of storage compared to the Control group. The citrus pulp
      groups significantly slowed down the rate of protein oxidation, indicating that
      dietary citrus pulp reduced oxidative changes in meat proteins.

PMID- 24583334
TI  - The antioxidant status and oxidative stability of muscle from lambs receiving
      oral administration of Artemisia herba alba and Rosmarinus officinalis essential
      oils.
AB  - The effect of the dietary supplementation to lambs of essential oils (EOs) from
      rosemary (Rosmarinus officinalis) and artemisia (Artemisia herba alba) on the
      antioxidant status of muscle and on meat oxidative stability was studied.
      Eighteen Barbarine lambs were divided into 3 groups and for 95days received oat
      hay and concentrates. One group (C) was not supplemented, while the other two
      groups received 400mg/kg of EOs from rosemary (R400) or artemisia (A400). Both
      EOs possessed antioxidant properties and their oral administration improved the
      reducing and radical scavenging capacity of the muscle compared to the C
      treatment (P<0.01). Nevertheless, supplementing EOs did not exert protection
      against lipid oxidation and did not affect the colour stability in meat over
      7days of aerobic storage. 

PMID- 24583335
TI  - Angiostrongylus cantonensis eosinophilic meningitis: a clinical study of 42
      consecutive cases in French Polynesia.
AB  - INTRODUCTION: In endemic areas, eosinophilic meningitis is mainly caused by
      Angiostrongylus cantonensis. We describe a series of this poorly-known condition.
      METHODS: Retrospective cohort study (2000-2012) including all patients diagnosed
      with eosinophilic meningitis in French Polynesia. RESULTS: Forty-two patients
      (males: 61.9%, age: 22 (IQR 17-32)) were diagnosed with a serologically proven
      (n=13) or probable A. cantonensis meningitis, mostly during the dry season
      (66.6%) and following the consumption of or prolonged contact with an
      intermediate/paratenic host (64.3%). No differential diagnosis was found in
      probable cases, in whom serological tests were performed earlier (7.5 days (6.5
      10)) compared to positive patients (7.5 (6.5-10) versus 11 (7-30) days, p=0.02).
      The most commonly reported symptom was headache (92.8%). Fever (7.1%) and
      biological inflammatory syndrome (14.3%) were rare. Blood eosinophil count was
      1200/mm(3) (900-2548). Cerebrospinal fluid (CSF) analysis disclosed a protein
      level of 0.9 g/L (0.7-1.1), a CSF/plasma glucose ratio of 0.50 (0.40-0.55), and
      500 leucocytes/mm(3) (292-725; eosinophils: 42.0% (29.5-60); lymphocytes: 46.5%
      (32.5-59.0)). Thirteen cases (31.0%) were severe, with 11 focal neurological
      deficits. A delayed hospital referral (OR 1.13, p=0.05) was associated with
      severity. CONCLUSIONS: A. cantonensis meningitis must be evocated in young
      patients with meningitic syndrome, severe headache, and CSF inflammation with
      predominance of eosinophils.

PMID- 24583336
TI  - Basal MU-opioid receptor availability in the amygdala predicts the inhibition of
      pain-related brain activity during heterotopic noxious counter-stimulation.
AB  - The aim of this study was to investigate the association between the magnitude of
      anti-nociceptive effects induced by heterotopic noxious counter-stimulation
      (HNCS) and the basal MU-opioid receptor availability in the amygdala. In 8
      healthy volunteers (4 females and 4 males), transcutaneous electrical stimulation
      was applied to the right sural nerve to produce the nociceptive flexion reflex
      (RIII-reflex), moderate pain, and scalp somatosensory evoked potentials (SEPs).
      Immersion of the left hand in cold water for 20min was used as HNCS. In a
      separate session, basal MU-opioid receptor availability was measured using
      positron emission tomography with the radiotracer [(11)C]carfentanil. HNCS
      produced a reduction of the P260 amplitude (p<0.05), a late component of SEP that
      reflects activity in the anterior cingulate cortex. This reduction was associated
      with higher basal MU-opioid receptor availability in the amygdala on the right
      (R(2)=0.55, p=0.03) with a similar trend on the left (R(2)=0.24, p=0.22).
      Besides, HNCS did not induce significant changes in pain and RIII-reflex
      amplitude (p>0.05). These results suggest that activation of MU-opioid receptors
      in the amygdala may contribute to the anti-nociceptive effects of HNCS. The lack
      of RIII-reflex modulation further suggests that MU-opioid receptor activation in
      the amygdala contributes to decrease pain-related brain activity through a
      cerebral mechanism independent of descending modulation. 

PMID- 24583337
TI  - An analysis of cerebral blood flow from middle cerebral arteries during cognitive
      tasks via functional transcranial Doppler recordings.
AB  - Functional transcranial Doppler (fTCD) is a useful medical imaging technique to
      monitor cerebral blood flow velocity (CBFV) in major cerebral arteries. In this
      paper, CBFV changes in the right and left middle cerebral arteries (MCA) caused
      by cognitive tasks, such as word generation tasks and mental rotation tasks, were
      examined using fTCD. CBFV recordings were collected from 20 healthy subjects (10
      females, 10 males). We obtained both the raw CBFV signal and the envelope CBFV
      signal, which is the maximal velocity to gain more information about the changes
      and hemisphere lateralization in cognitive tasks compared to the resting state.
      Time, frequency, time-frequency, and information-theoretic features were
      calculated and compared. Sex effects were also taken into consideration. The
      results of our analysis demonstrated that the raw CBFV signal contained more
      descriptive information than the envelope signals. Furthermore, both types of
      cognitive tasks produced higher values in most signal features. Geometric tasks
      were more distinguished from the rest-state than verbal tasks and the
      lateralization was exhibited in right MCA during geometric tasks. Our results
      show that the raw CBFV signals provided valuable information when studying the
      effects of cognitive tasks and lateralization in the MCA. 

PMID- 24583338
TI  - Valproic acid inhibits excess dopamine release in response to a fear-conditioned
      stimulus in the basolateral complex of the amygdala of methamphetamine-sensitized
      rats.
AB  - Valproic acid, an established antiepileptic and antimanic drug, has recently
      emerged as a promising emotion-stabilizing agent for patients with psychosis.
      Although dopamine transmission in the amygdala plays a key role in emotional
      processing, there has been no direct evidence about how valproic acid acts on the
      dopaminergic system in the brain during emotional processing. In the present
      study, we tested the effect of valproic acid on a trait marker of vulnerability
      to emotional stress in psychosis, which is excess dopamine release in response to
      a fear-conditioned stimulus (CS) in the basolateral complex of the amygdala of
      methamphetamine-sensitized rats. Extracellular dopamine was collected from the
      amygdala of freely moving methamphetamine-sensitized rats by in vivo
      microdialysis and was measured using high-performance liquid chromatography.
      During microdialysis, valproic acid was intraperitoneally injected followed by CS
      exposure. Valproic acid treatment decreased baseline levels of dopamine and also
      attenuated the excess dopamine release in response to the CS in the amygdala of
      methamphetamine-sensitized rats. The results prove that valproic acid inhibits
      spontaneous dopamine release and also attenuates excess dopaminergic signaling in
      response to emotional stress in the amygdala. These findings suggest that the
      mechanisms of the emotion-stabilizing effect of valproic acid in psychosis
      involve modulation of dopaminergic transmission in emotional processing. 

PMID- 24583339
TI  - Mechanisms of angiotensin converting enzyme inhibitor-induced IOP reduction in
      normotensive rats.
AB  - Angiotensin converting enzyme inhibitors (ACEIs) have been shown to lower
      intraocular pressure (IOP). Since, the ACEIs cause increased tissue prostaglandin
      levels, we hypothesized that the mechanisms of ACEI-induced IOP reduction have
      similarity with those of prostaglandin analogs. The present study investigated
      the involvement of matrix metalloproteinases (MMPs) and cytokine activity
      modulation as the underlying mechanisms of ACEI-induced ocular hypotension. The
      IOP lowering effect of single drop of enalaprilat dehydrate 1% was evaluated in
      rats pretreated with a broad spectrum MMP inhibitor or a cytokine inhibitor.
      Effect of angiotensin receptor blocker, losartan potassium 2%, was also studied
      to evaluate involvement of angiotensin II receptor type 1 (AT1) in IOP lowering
      effect of ACEI. Topical treatment with single drop of enalaprilat resulted in
      significant IOP reduction in treated eye with mean peak reduction 20.3% at 3h
      post-instillation. Treatment with losartan resulted in a peak IOP reduction of
      13.3%, which was significantly lower than enalaprilat, indicating involvement of
      mechanisms in addition to AT1 blockade. Pretreatment with a broad spectrum MMP
      inhibitor or a cytokine inhibitor significantly attenuated the enalprilat-induced
      IOP reduction with mean peak IOP reduction of 11.2% and 13.6% respectively. The
      IOP-lowering effect of enalaprilat seems to be attributed to reduced angiotensin
      II type 1 receptor stimulation and modulation of MMP and cytokines activities. 

PMID- 24583340
TI  - UCH-L1 induces podocyte hypertrophy in membranous nephropathy by protein
      accumulation.
AB  - Podocytes are terminally differentiated cells of the glomerular filtration
      barrier that react with hypertrophy in the course of injury such as in membranous
      nephropathy (MGN). The neuronal deubiquitinase ubiquitin C-terminal hydrolase L1
      (UCH-L1) is expressed and activated in podocytes of human and rodent MGN. UCH-L1
      regulates the mono-ubiquitin pool and induces accumulation of poly-ubiquitinated
      proteins in affected podocytes. Here, we investigated the role of UCH-L1 in
      podocyte hypertrophy and in the homeostasis of the hypertrophy associated "model
      protein" p27(Kip1). A better understanding of the basic mechanisms leading to
      podocyte hypertrophy is crucial for the development of specific therapies in MGN.
      In human and rat MGN, hypertrophic podocytes exhibited a simultaneous up
      regulation of UCH-L1 and of cytoplasmic p27(Kip1) content. Functionally,
      inhibition of UCH-L1 activity and knockdown or inhibition of UCH-L1 attenuated
      podocyte hypertrophy by decreasing the total protein content in isolated
      glomeruli and in cultured podocytes. In contrast, UCH-L1 levels and activity
      increased podocyte hypertrophy and total protein content in culture, specifically
      of cytoplasmic p27(Kip1). UCH-L1 enhanced cytoplasmic p27(Kip1) levels by nuclear
      export and decreased poly-ubiquitination and proteasomal degradation of
      p27(Kip1). In parallel, UCH-L1 increased podocyte turnover, migration and
      cytoskeletal rearrangement, which are associated with known oncogenic functions
      of cytoplasmic p27(Kip1) in cancer. We propose that UCH-L1 induces podocyte
      hypertrophy in MGN by increasing the total protein content through altered
      degradation and accumulation of proteins such as p27(Kip1) in the cytoplasm of
      podocytes. Modification of both UCH-L1 activity and levels could be a new
      therapeutic avenue to podocyte hypertrophy in MGN. 

PMID- 24583341
TI  - Epothilone B induces extrinsic pathway of apoptosis in human SKOV-3 ovarian
      cancer cells.
AB  - The molecular mechanisms underlying epothilone B (EpoB) induced apoptosis were
      investigated in SKOV-3 human ovarian cancer cells. The aim of this research was
      to compare EpoB's, which belongs to the new class of anticancer drugs, with
      paclitaxel's (PTX) ability to induce apoptosis. The mode of cell death was
      assessed colorimetrically, fluorimetrically and by immunoblot analyses through
      measuring DNA fragmentation, the level of intracellular calcium, the level of
      cytochrome c, TRAIL, the cleavage of poly(ADP-ribose) polymerase (PARP) and the
      activation of caspase-9, -8 and -3. EpoB leads to an increase of the cytosolic
      level of cytochrome c after 4 h of cell treatment. After 24 and 48 h of cell
      treatment the level of intracellular calcium also increased by about 21% and 24%
      respectively. Moreover, EpoB, similarly to PTX, promoted the expression of TRAIL
      in lymphocytes, although high TRAIL expression on tumor cells was detected only
      after adding EpoB to SKOV-3 cells. EpoB mediates caspases-8 and -3 activation,
      which is independent of the reduction in the amount of caspase-9. Epitope
      specific monoclonal and polyclonal antibodies revealed characteristic apoptotic
      changes that included cleavage of the 116 kDa PARP polypeptide to 25 kDa
      fragments. The results of our study show that EpoB induces mainly the extrinsic
      pathway.

PMID- 24583342
TI  - Palmatine activates AhR and upregulates CYP1A activity in HepG2 cells but not in
      human hepatocytes.
AB  - The protoberberine alkaloid palmatine is present in preparations from medicinal
      plants such as Coptis chinensis and Corydalis yanhusuo. This study examined
      whether palmatine affects the expression of cytochromes P450 (CYPs) 1A1 and 1A2
      in primary cultures of human hepatocytes and human hepatoma HepG2 cells grown as
      monolayer or spheroids. Gene reporter assays showed that palmatine significantly
      activated the aryl hydrocarbon receptor (AhR) and increased the activity of
      CYP1A1 gene promoter in transiently transfected HepG2 cells. In HepG2 monolayer
      culture, palmatine also significantly increased mRNA and activity levels of
      CYP1A1, albeit with considerably less potency than 2,3,7,8-tetrachlorodibenzo-p
      dioxin, a prototypical CYP1A inducer. On the other hand, CYP1A activity was not
      significantly elevated by palmatine in HepG2 spheroids. Moreover, palmatine
      induced mild or negligible changes in CYP1A1 and CYP1A2 mRNA expression without
      affecting CYP1A activity levels in primary human hepatocytes. It is concluded
      that palmatine activates the AhR-CYP1A pathway in HepG2 monolayer, while the
      potential for CYP1A induction is irrelevant in cell systems which are closer to
      the in vivo situation, i.e. in HepG2 spheroids and primary cultures of human
      hepatocytes. Possible induction of CYP1A enzymes by palmatine in vivo remains to
      be investigated. 

PMID- 24583343
TI  - Biochemical functions of the glutathione transferase supergene family of Larix
      kaempferi.
AB  - Glutathione transferases (GSTs), which are ubiquitous in plants, play a major
      role in the detoxification of xenobiotics and oxidative stress metabolism. Due to
      their role in herbicide detoxification, previous studies of plant GSTs have
      mainly focused on agricultural plants. In contrast, functional information
      regarding gymnosperm GSTs is scarce. In this study, we cloned 27 full-length GST
      genes from the deciduous conifer Larix kaempferi, which is widely distributed
      across the cooler regions of the northern hemisphere. As with the angiosperm GST
      gene family, Larix GSTs are divided into eight classes, and tau class GSTs are
      the most numerous. Compared to the other seven classes of GSTs, Larix tau GST
      genes show substantially more variation in their expression patterns. The
      purified Larix GST proteins showed different substrate specificities, substrate
      activities, and kinetic characteristics. The pH and temperature profiles of
      purified Larix GST proteins showed broad optimum pH and temperature ranges for
      enzymatic activity, suggesting that Larix GSTs have evolutionary adaptations to
      various adverse environments. Taken together, this study provides comprehensive
      insight into the gymnosperm GST gene family. 

PMID- 24583344
TI  - Molecular cloning and expression analysis of mulberry MAPK gene family.
AB  - Mitogen-activated protein kinase (MAPK) cascades play an important role in
      regulating various biotic and abiotic stresses in plants. Although MAPKs have
      been identified and characterized in a few model plants, there is little
      information available for mulberry Morus sp. L., one of the most ecologically and
      economically important perennial trees. This study identified 47 mulberry Morus
      notabilis MAPK (MnMAPK) family genes: 32 MnMAPKKK, five MnMAPKK and ten MnMAPK
      genes, and cloned ten MnMAPK cDNA genes based on a genome-wide analysis of the
      morus genome database. Comparative analysis with MAPK gene families from other
      plants suggested that MnMAPKs could be divided into five subfamilies (groups A,
      B, C, D and E) and they could have similar functions in response to abiotic and
      biotic stresses. MnMAPK gene expression analysis of different stresses (high/low
      temperature, salt and drought) and signal molecules (ABA, SA, H2O2 and methyl
      jasmonate (MeJA)) revealed that all ten MnMAPK genes responded to high/low
      temperature, salt and drought stresses, and that nine of the ten MnMAPKs (MnMAPK7
      excepted) could be induced by ABA, SA, H2O2 and MeJA, which suggested that
      MnMAPKs may play pivotal roles in signal transduction pathways. Our results
      indicated that almost all of the MnMAPKs may be involved in environmental stress
      and defense responses, which provides the basis for further characterization of
      the physiological functions of MnMAPKs. 

PMID- 24583345
TI  - Modeling growth of Escherichia coli O157:H7 in fresh-cut lettuce treated with
      neutral electrolyzed water and under modified atmosphere packaging.
AB  - The purpose of this study was to evaluate and model the growth of Escherichia
      coli O157:H7 in fresh-cut lettuce submitted to a neutral electrolyzed water (NEW)
      treatment, packaged in passive modified atmosphere and subsequently stored at
      different temperatures (4, 8, 13, 16 degrees C) for a maximum of 27 days. Results
      indicated that E. coli O157:H7 was able to grow at 8, 13, and 16 degrees C, and
      declined at 4 degrees C. However at 8 degrees C, the lag time lasted 19 days,
      above the typical shelf-life time for this type of products. A secondary model
      predicting growth rate as a function of temperature was developed based on a
      square-root function. A comparison with literature data indicated that the growth
      predicted by the model for E. coli O157:H7 was again lower than those observed
      with other disinfection treatments or packaging conditions (chlorinated water,
      untreated product, NEW, etc.). The specific models here developed might be
      applied to predict growth in products treated with NEW and to improve existing
      quantitative risk assessments.

PMID- 24583346
TI  - Quantitation OF ARGS aggrecan fragments in synovial fluid, serum and urine from
      osteoarthritis patients.
AB  - OBJECTIVE: To characterise ARGS neoepitope concentrations in various matrices
      from patients with knee osteoarthritis (OA) and assess performance of an
      immunoassay to facilitate clinical development of therapeutics affecting the A
      disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS-5)
      pathway. DESIGN: Matched sera, urine, and synovial fluid (SF) (surgical subjects
      only) were collected from healthy subjects, subjects with knee OA (non-surgical
      OA), and OA subjects undergoing total knee replacement (OA-TKR; n = 20 per
      group). Diurnal and inter-day variation was evaluated in the non-surgical OA
      group over 3 separate visits. Serum and urine samples were collected on two
      visits for the OA-TKR group with SF taken only at the time of surgery. ARGS
      neoepitope was quantitated using an optimized immunoassay. RESULTS: Serum ARGS
      neoepitope concentrations were elevated in OA-TKR subjects compared to non
      surgical OA subjects (P = 0.005) and healthy subjects (P = 0.0002). Creatinine
      corrected urinary ARGS neoepitope concentrations were more variable, but were
      also elevated in the OA-TKR subjects compared to healthy subjects (P = 0.008). No
      significant diurnal effect or inter-day variance was observed in serum or urine.
      Serum ARGS neoepitope concentrations correlated with age (P = 0.0252) but not
      with total number of joints with OA involvement. SF ARGS neoepitope
      concentrations correlated with Western Ontario and MacMaster OA Index (WOMAC)
      stiffness score (P = 0.04) whereas a weaker, non-significant trend towards
      positive correlation with combined WOMAC score and the number of concurrent
      joints was observed. CONCLUSIONS: This study utilized a sensitive and robust
      assay to evaluate ARGS neoepitope concentrations in various matrices in OA
      patients and healthy volunteers. ARGS neoepitope appears promising as a
      prognostic/stratification marker to facilitate patient selection and as an early
      pharmacodynamic marker for OA therapeutic trials.

PMID- 24583347
TI  - Identification and analysis of a SMAD3 cis-acting eQTL operating in primary
      osteoarthritis and in the aneurysms and osteoarthritis syndrome.
AB  - OBJECTIVE: The TGF-beta pathway plays a central role in joint development with
      polymorphism in TGF-beta pathway genes implicated in osteoarthritis
      susceptibility. One association is to rs12901499, within intron 1 of SMAD3. Since
      rs12901499 is not in linkage disequilibrium with a non-synonymous polymorphism,
      it is likely the association is operating by influencing expression of SMAD3.
      DESIGN: Using tissues from the joints of primary osteoarthritis patients who had
      undergone joint replacement we measured the overall expression of SMAD3 by
      quantitative real-time PCR. We also measured allelic expression of SMAD3 using
      these tissues and vascular smooth muscle cells from patients with aneurysms and
      osteoarthritis syndrome, a rare condition featuring early-onset osteoarthritis.
      We tested the functional effect of SNPs in vitro using luciferase assays and
      assessed association with osteoarthritis using a large osteoarthritis case
      control dataset. RESULTS: We observed that genotype at rs12901499 did not
      correlate with overall SMAD3 expression or allelic expression. However, genotype
      at a 3'UTR SNP, rs8031440, did correlate with SMAD3 expression in cartilage (P =
      0.005) which was supported by allelic expression data showing that the G allele
      correlated with decreased SMAD3 expression in joint tissues and vascular smooth
      muscle cells. This G allele was underrepresented in osteoarthritis cases vs
      controls (P = 0.027, odds ratio = 0.921). rs8031440 is in perfect linkage
      disequilibrium with five other SMAD3 3'UTR SNPs and our luciferase analysis
      identified rs3743342 and rs12595334 as being functional. CONCLUSION: SMAD3 is
      subject to cis-acting regulatory polymorphism in the tissues of relevance to both
      primary osteoarthritis and the aneurysms-osteoarthritis syndrome.

PMID- 24583348
TI  - Association between delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) and
      joint space narrowing and osteophytes: a cohort study in patients with partial
      meniscectomy with 11 years of follow-up.
AB  - OBJECTIVE: To examine the association between the relaxation time (T1Gd) of
      delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) and
      grade of tibiofemoral joint space narrowing (JSN) and osteophytosis 11 years
      later, in a cohort of meniscectomized patients. DESIGN: Patients (n = 45) aged 35
      50 who had undergone an arthroscopic partial medial meniscectomy 1-6 years
      earlier, due to degenerative meniscal tear, were examined using dGEMRIC. These
      patients had no cartilage changes defined as deep clefts or visible bone at the
      time of arthroscopy. Eleven years later (12-16 years after surgery) 34 of these
      subjects (76%) were evaluated by weight-bearing knee radiography, and
      tibiofemoral joint changes were graded according to the Osteoarthritis Research
      Society International Atlas. RESULTS: Lower T1Gd in the medial compartment was
      associated with higher grade of medial JSN (grade 0, 351 ms; grade 1, 386 ms;
      grade 2, 342 ms; grade 3, 259 ms [P for trend < 0.001]) and more osteophytosis
      (score 0, 371 ms; score 1, 389 ms; score 2, 354 ms; score 3, 289 ms; score 4, 265
      ms; score 5, 275 ms [P for trend = 0.001]). Lower T1Gd in the lateral compartment
      was associated with higher grade of lateral JSN (grade 0, 436 ms; grade 1, 346 ms
      [P for trend = 0.026]). CONCLUSION: The current study suggests that lower T1Gd
      measured with dGEMRIC of medial and lateral femoral cartilage is associated with
      higher grade of JSN 11 years later, and medially, also with more osteophytosis.

PMID- 24583349
TI  - In search of Flavivirus inhibitors part 2: tritylated, diphenylmethylated and
      other alkylated nucleoside analogues.
AB  - Several flaviviruses, such as the yellow fever virus and the dengue virus cause
      severe and potentially lethal infection in man. Following up on our initial hit
      3',5'-bistritylated uridine 1, a series of alkylated nucleoside analogues were
      synthesized and evaluated for their in vitro antiviral activities against dengue
      fever virus and yellow fever virus. Hereto, alkyl and aryl groups were attached
      at various positions of the sugar ring combined with subtle variation of the
      heterocyclic base. Among the new series of derivatives, 3',5'-di-O-trityl-5
      fluoro-2'-deoxyuridine (39) was the most efficient in this series and inhibited
      both yellow fever virus and dengue virus replication with a 50% effective
      concentration (EC50) of ~1 MUg/mL without considerable cytotoxicity. The other
      fluorinated derivatives proved more toxic. Almost all diphenylmethylated
      pyrimidine nucleosides with 3',5'-di-O-benzhydryl-2'-deoxyuridine (50) as the
      example were endowed with strong cytotoxic effects down to 1 MUg/mL.

PMID- 24583350
TI  - Development of antimycobacterial tetrahydrothieno[2,3-c]pyridine-3-carboxamides
      and hexahydrocycloocta[b]thiophene-3-carboxamides: Molecular modification from
      known antimycobacterial lead.
AB  - Twenty derivatives of 2,6-disubstituted 4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3
      carboxamide and ten of 2-substituted 4,5,6,7,8,9-hexahydrocycloocta[b]thiophene-3
      carboxamide were synthesized by molecular modification of a known
      antimycobacterial molecule. Compounds were evaluated in vitro against
      Mycobacterium tuberculosis (MTB), and cytotoxicity against RAW 264.7 cell line.
      Among the compounds, 2-(4-phenoxybenzamido)-4,5,6,7,8,9
      hexahydrocycloocta[b]thiophene-3-carboxamide (12f) was found to be the most
      active compound against MTB with MIC of 3.70 MUM and was more potent than
      Ethambutol (MIC of 7.64 MUM), Ciprofloxacin (MIC of 9.41 MUM) and standard lead
      compound SID 92097880 (MIC of 9.15 MUM). Compound 12f also showed MTB MIC of 1.23
      MUM in the presence of an efflux pump inhibitor verapamil, and showed no
      cytotoxicity at 50 MUM.

PMID- 24583351
TI  - Anti-proliferative activity of 2,6-dichloro-9- or 7-(ethoxycarbonylmethyl)-9H- or
      7H-purines against several human solid tumour cell lines.
AB  - As leads we took several benzo-fused seven- and six-membered scaffolds linked to
      the pyrimidine or purine moieties with notable anti-proliferative activity
      against human breast, colon and melanoma cancerous cell lines. We then decided to
      maintain the double-ringed nitrogenous bases and change the other components to
      the ethyl acetate moiety. This way six purine and two 5-fluorouracil derivatives
      were obtained and evaluated against the MCF-7, HCT-116, A-375 and G-361 cancer
      cell lines. Two QSARs are obtained between the anti-proliferative IC50 values for
      compounds 26-33 and the clog P against the melanoma cell lines A-375 and G-361.
      Our results show that two of the analogues [ethyl 2-(2,6-dichloro-9H- or 7H
      purine-9- or 7-yl)acetates (30 and 33, respectively)] are potent cytotoxic agents
      against all the tumour cell lines assayed, showing single-digit micromolar IC50
      values. This exemplifies the potential of our previously reported purine
      compounds to qualify as lead structures for medicinal chemistry campaigns,
      affording simplified analogues easy to synthesize and with a noteworthy
      bioactivity. The selective activity of 30 and 33 against the melanoma cell line A
      375, via apoptosis, supposes a great advantage for a future therapeutic use.

PMID- 24583352
TI  - Homoisoflavonoids as potential imaging agents for beta-amyloid plaques in
      Alzheimer's disease.
AB  - A series of homoisoflavonoids [(E)-3-benzylidenechroman-4-ones, 3a-l] as novel
      potential diagnostic imaging agents targeting beta-amyloid (Abeta) plaques in
      Alzheimer's disease (AD) were synthesized and evaluated. In vitro binding studies
      using Abeta1-40 aggregates with [(125)I]IMPY as the reference ligand showed that
      these compounds demonstrated high to low binding affinities at the K(i) values
      ranged from 9.10 to 432.03 nM, depending on the substitution of the phenyl ring.
      Fluorescent staining in vitro indicated that one compound with a N,N
      dimethylamino group intensely stained Abeta plaques within brain sections of
      postmortem AD patients. Biodistribution studies in normal mice after i.v.
      injection of the radioiodinated homoisoflavonoid displayed good initial brain
      uptake (2.61% ID/g at 2 min postinjection) and rapid clearance from the brain
      (0.18% ID/g at 60 min), which is desirable for amyloid imaging agents. The
      results strongly suggest that these derivatives are worthy of further study and
      may be useful amyloid imaging agents for early detection of amyloid plaques in
      the brain of AD.

PMID- 24583353
TI  - The applications of binuclear metallohydrolases in medicine: recent advances in
      the design and development of novel drug leads for purple acid phosphatases,
      metallo-beta-lactamases and arginases.
AB  - Binuclear metallohydrolases are a family of proteins that can be targeted for
      drug discovery. The common feature of these enzymes is the presence of two
      closely spaced metal ions (i.e. less than 4 A apart) that capture a water
      molecule that is used as a nucleophile in highly specific hydrolytic reactions.
      In this mini-review we describe what is known about the biological and catalytic
      activity, three-dimensional structure and inhibition for three prominent drug
      targets in this family of enzymes, (i) purple acid phosphatases, (ii) metallo
      beta-lactamases and (iii) arginases. These enzymes are targets for the
      development of chemotherapeutics to treat a range of disorders including
      osteoporosis, cardiovascular disease and erectile dysfunctions, but also to stem
      the spread of antibiotic resistance, a major threat to global health care.

PMID- 24583354
TI  - Synthesis, structures, spectroscopy and antimicrobial properties of complexes of
      copper(II) with salicylaldehyde N-substituted thiosemicarbazones and 2,2'
      bipyridine or 1,10-phenanthroline.
AB  - Among the biometals (Cu, Co, Ni-cofactors in many enzymes), copper derivatives of
      O, N, S-donor salicylaldehyde thiosemicarbazones have received considerable
      attention owing to their potential biological applications. Eight new complexes
      of salicylaldehyde-N-substituted thiosemicarbazones [5-MeO-2-HO-C6H4-C(2)(H)N(3)
      N(2)H-C(1)(S)-N(1)HR; R = Me, H2L(1); Et, H2L(1), Ph, H2L(3), H, H2L(4)] with
      copper(II), namely, [Cu(kappa(3)-O,N,S-L)( kappa(2)-N,N-L')] {(L)(2-) = (L(1))(2
      ), L' = bipy, 1, phen, 2; (L)(2-) = (L(2))(2-), L' = bipy, 3, phen, 4; (L)(2-) =
      (L(3))(2-), L' = bipy, 5, phen, 6; (L)(2-) = (L(4))(2-), L' = bipy, 7, phen, 8}
      have been isolated. Complexes have slightly distorted square pyramidal geometry
      around the metal center (tau parameter = 0.243-0.357) and display weak to intense
      fluorescence in the region, 375-475 nm. These copper complexes have shown
      significant growth inhibitory activity (antimicrobial activity) against
      Staphylococcus aureus (MTCC740), methicillin resistant Staphylococcus aureus
      (MRSA), Klebsiella pneumoniae 1 (MTCC109), Shigella flexneri (MTCC1457),
      Pseudomonas aeruginosa (MTCC741) and Candida albicans (MTCC227). The activity
      against MRSA is an interesting observation as the commercially available
      gentamycin is found to be inactive against this bacterial strain. Specifically
      complex 5 formed by 5-methoxysalicylaldehyde-N-phenylthiosemicatbazone has shown
      novel antimicrobial activity against various bacteria and yeast investigated.

PMID- 24583355
TI  - Design and synthesis of potent antitumor water-soluble phenyl N-mustard
      benzenealkylamide conjugates via a bioisostere approach.
AB  - A series of new, water-soluble phenyl N-mustard-benzenealkylamide conjugates
      containing hydrophilic omega-dialkylaminoalkylamide or omega-cyclic
      aminoalkylamide moieties were synthesized via a bioisostere approach. These
      compounds have a broad spectrum of antitumor activity against a panel of human
      tumor cell lines. Of these derivatives, compound 18b effectively suppressed the
      growth of colon cancer (HCT-116), prostate cancer (PC3), and lung cancer (H460)
      xenografts. The growth of HCT-116 xenografts was almost completely suppressed
      when co-treated with compound 18b and 5-fluorouracil. Furthermore, compound 18b
      can induce DNA cross-linking and cell-cycle arrest at the G2/M phase. Early
      preclinical studies, including pharmacokinetics in rats, inhibition of the hERG,
      and 14 days of acute intravenous injection toxicity, suggest that compound 18b is
      a promising candidate for further preclinical studies. 

PMID- 24583356
TI  - Bifunctional ethyl 2-amino-4-methylthiazole-5-carboxylate derivatives: synthesis
      and in vitro biological evaluation as antimicrobial and anticancer agents.
AB  - Thirty thiazole compounds bearing chemotherapeutically-active pharmacophores were
      synthesized and evaluated for their preliminary in vitro antimicrobial and
      anticancer activities. Nineteen compounds displayed obvious antibacterial
      potential, with special bactericidal activity against Gram positive bacteria,
      whereas, nine analogs showed moderate to weak antifungal activity against Candida
      albicans. The analog 12f proved to be the most active antimicrobial member
      identified in this study being comparable to ampicillin and gentamicin sulfate
      against Staphylococcus aureus and Bacillus subtilis, together with a moderate
      antifungal activity. Additionally, nine derivatives were tested for their
      preliminary in vitro anticancer activity according to the current one-dose
      protocol of the NCI. Compound 9b revealed a broad spectrum of anticancer activity
      against 29 out of the tested 60 subpanel tumor cell lines. Collectively,
      compounds 4, 9b, 10b and 12f could be considered as promising dual anticancer
      antibiotics.

PMID- 24583357
TI  - Recent advances in the structural library of functionalized quinazoline and
      quinazolinone scaffolds: synthetic approaches and multifarious applications.
AB  - Drug development has been a principal driving force in the rapid maturation of
      the field of medicinal chemistry during the past several decades. During this
      period, the intriguing and challenging molecular architectures of nitrogen
      containing heterocycles with potential bioactive properties have received
      significant attention from researchers engaged in the areas of natural product
      synthesis and heterocyclic methodology, and constituted a continuous stimulus for
      development in bio(organic) chemistry. In this perspective, the current review
      article is an effort to summarize recent developments in the environmentally
      benign synthetic methods providing access to quinazoline and quinazolinone
      scaffolds with promising biological potential. This article also aims to discuss
      potential future directions on the development of more potent and specific
      analogues for various biological targets. 

PMID- 24583358
TI  - Reply to: "The importance of prognostic factors in cirrhosis".

PMID- 24583359
TI  - The importance of prognostic factors in cirrhosis.

PMID- 24583360
TI  - Characterization of ultrasound-induced pulmonary capillary hemorrhage in rats.
AB  - Routine pulmonary ultrasound for diagnosis of disease or injury relies on
      interpretation of image features, such as comet-tail artifacts, which can also be
      indicative of the poorly understood phenomenon of ultrasound-induced pulmonary
      capillary hemorrhage (PCH). Evans blue extraction and bronchoalveolar lavage
      (BAL) were evaluated for assessment of PCH induced by ultrasound scanning. Rats
      anesthetized with ketamine with or without xylazine received sham or scanning for
      5 min with a 7.6 MHz linear array. Evans blue extraction and BAL albumin
      measurements failed to demonstrate significant increases for scanning, even
      though the induction of comet-tail artifacts was significant. BAL cell counts had
      an insignificant increase relative to shams at a near-threshold mechanical index
      (MI) of 0.52 (P=0.07), but a highly significant increase at MI=0.9 (P=0.001). The
      possibility of xylazine-induced elevated albumin was tested, but no significant
      decrease was found for sham or scanned rats with ketamine-only anesthesia.
      Interestingly, without xylazine, the widths of comet-tail artifacts in the
      ultrasound images were significantly smaller (P=0.001) and cell counts in BAL
      fluid also were reduced (P=0.014). The BAL cell-count method provides a valuable
      additional means of PCH quantification.

PMID- 24583361
TI  - Induction of human plasmablasts during infection with antibiotic-resistant
      nosocomial bacteria.
AB  - OBJECTIVES: Nosocomial pathogens such as Acinetobacter baumannii are a growing
      public health threat, due in part to their increasing resistance to antibiotics.
      Since some strains are resistant to all available antibiotics, novel therapies
      are urgently needed. Plasmablasts are short-lived B cells found in the blood that
      can be collected and harnessed to produce therapeutic antibodies. We set out to
      determine whether plasmablasts are induced during infection with A. baumannii and
      other nosocomial pathogens. METHODS: We obtained blood samples from patients
      infected with antibiotic-resistant nosocomial pathogens, and analysed their
      plasmablast response by flow cytometry. RESULTS: We observed a strong induction
      of plasmablasts in patients with antibiotic-resistant A. baumannii infection.
      Furthermore, plasmablasts were also induced in response to other drug-resistant
      nosocomial pathogens. CONCLUSIONS: These data suggest that plasmablasts may be
      broadly harnessed to develop therapeutic antibodies to combat otherwise
      untreatable antibiotic-resistant infections.

PMID- 24583362
TI  - Emergence of a multiresistant KPC-3 and VIM-1 carbapenemase-producing Escherichia
      coli strain in Spain.
AB  - OBJECTIVES: To characterize the mechanisms involved in carbapenem resistance, as
      well as the genetic elements supporting their mobilization, in a multidrug
      resistant Escherichia coli isolate. METHODS: The E. coli isolate was obtained
      from a patient with fatal urinary sepsis. Antimicrobial susceptibility testing
      was performed by the disc diffusion and agar dilution methods. The E. coli
      molecular type and phylogroup were determined using multilocus sequence typing
      and the triple PCR technique, respectively. PCR and sequencing were used for
      virulence and resistance genotype characterization. Plasmid content and gene
      location were analysed by S1-PFGE, I-Ceu1-PFGE and hybridization experiments.
      Transformation assays were performed. RESULTS: The E. coli strain, typed as ST448
      and phylogroup B1, was resistant to all tested antibiotics except fosfomycin,
      tigecycline and tetracycline. The following resistance and virulence genetic
      structures were obtained: ISKpn7 + bla(KPC-3) + ISKpn6 linked to Tn4401; tnpR +
      aac(6')-Ib'-9 + aadA1 + bla(OXA-9) + tnpR + bla(TEM-1a) + tnpB + strB + strA +
      sul2; intI1 + bla(VIM-1) + aac(6')-Ib' + aphA15 + aadA1 + catB2 + qacEDelta1-sul1
      + orf5; ISEcp1 + bla(CMY-2); IS26 + bla(SHV-12); aph(3')-I; aac(3)-IV; floR;
      catA; and fimA. Mutations in the ampC promoter (-18, -1 and +58) and
      substitutions in the GyrA (Ser-83->Leu and Asp-87->Asn) and ParC (Ser-80->Ile)
      proteins were observed. IncFII (ST2), IncA/C and ColE(TP) plasmids of 145.5, 87
      and <2 kb, respectively, were found. The bla(VIM-1) gene was located in a non
      typeable plasmid of >300 kb, and the bla(KPC-3) gene in the 145.5 kb IncFII
      plasmid. Transformant strains carried the IncFII and ColE(TP) plasmids, and the
      bla(KPC-3), bla(TEM-1a), bla(OXA-9), aadA1, aac(6')-Ib'-9, aac(3)-IV and floR
      genes. CONCLUSIONS: This is the first report of the co-production of KPC-3, VIM
      1, SHV-12, OXA-9 and CMY-2 in a unique clinical multiresistant E. coli isolate.
      The dissemination of these genes on mobile genetic elements is alarming and
      complicates antimicrobial therapies.

PMID- 24583364
TI  - Comparison of tissue damages caused by endoscopic lumbar discectomy and
      traditional lumbar discectomy: a randomised controlled trial.
AB  - OBJECTIVES: This study aimed to compare the clinical efficacies of percutaneous
      endoscopic lumbar discectomy (PELD) and traditional open lumbar discectomy (OD).
      METHODS: The pre-operative and post-operative blood loss, hospital stays and
      wound sizes of the patients in the two groups were recorded. Enzyme-Linked
      immunosorbent assay was used to measure the changes of interleukin-6 (IL-6), C
      reactive protein (CRP) and creatine phosphokinase (CPK) pre-operation and 1 h, 6
      h, 12 h, 24 h and 48 h after corresponding surgery. Visual Analog Scale and
      Modified MacNab Criteria were used to assess post-operative results. RESULTS:
      Patients in the PELD group had less blood loss (p < 0.01), shorter
      hospitalization hours (p < 0.01) and smaller surgical wounds (p < 0.01) than the
      patients underwent traditional OD surgery. MacNab evaluated that the levels of
      satisfaction were above 90% in both groups post-operative six months. There was
      no significant difference in pain index between the two groups (p > 0.05).
      Furthermore, the levels of CRP, CPK and IL-6 in the PELD group were all lower
      than those in the OD group with a significant difference (p < 0.01). CONCLUSION:
      The PELD had less damage to human tissues than the traditional OD. PELD has a
      clear promotional value in clinical.

PMID- 24583363
TI  - Familial aggregation of tobacco use behaviors among Amish men.
AB  - INTRODUCTION: Tobacco use is a complex behavior. The Old Order Amish community
      offers unique advantages for the study of tobacco use because of homogenous
      ancestral background, sociocultural similarity, sex-specific social norms
      regarding tobacco use, and large family size. Tobacco use in the Old Order Amish
      community is almost exclusively confined to males. METHODS: We examined
      characteristics of tobacco use and familial aggregation among 1,216 Amish males
      from cross-sectional prospectively collected data. Outcomes examined included
      ever using tobacco regularly, current use, quantity of use, duration of use, and
      frequency of use. RESULTS: Sixteen percent of Amish men were current tobacco
      users, with the majority reporting cigar use only. Higher rates of tobacco use
      were found among sons of fathers who smoked compared with sons of fathers who did
      not smoke (46% vs. 22%, p < .001) as well as among brothers of index cases who
      smoked compared with brothers of index cases who did not smoke (61% vs. 29%, p <
      .001). After controlling for shared household effects and age, heritability
      accounted for 66% of the variance in ever smoking regularly (p = .045).
      CONCLUSIONS: The familial patterns of tobacco use observed among Amish men
      highlight the important role of family in propagating tobacco use and support the
      usefulness of this population for future genetic studies of nicotine addiction.

PMID- 24583365
TI  - Computer navigation in total hip arthroplasty: a meta-analysis of randomized
      controlled trials.
AB  - OBJECTIVE: Traditional operation frequently depends on experience of doctors and
      anatomic landmark visual observation, which often leads to deviation in
      acetabular prosthesis implantation. Computer navigation technique greatly
      improves accuracy of prosthesis implantation. The present meta-analysis aimed at
      assessing the accuracy and clinical significance of computer navigation for
      acetabular implantation. METHODS: All studies published through March 2013 were
      systematically searched from PubMed, EMBnse, Science Direct, Cechrane library and
      other databases. Relevant journals or conference proceedings were searched
      manually. Only randomized controlled trials (RCTs) were included. Two independent
      reviewers identified and assessed the literature. Mean difference (MD) and Odds
      ratio (OR) of radiologic and clinical outcomes were pooled throughout the study
      between navigated and conventional THA. The meta-analysis was conducted by RevMan
      5.1 software. RESULTS: Thirteen studies were included in the review, with a total
      sample size of 1071 hips. Statistically significant differences were observed
      between navigated and conventional groups in the number of acetabular cups
      implanted beyond the safe zone [OR = 0.13, 95% confidence interval (CI) (0.08
      0.22); P < 0.00001], operative time [MD = 19.87 min, 95% CI (14.04-24.35); P <
      0.00001] and leg length discrepancy [MD = -4.16 mm, 95% CI (-7.74 to -1.48); P =
      0.004]. No significant differences in cup inclination, anteversion, incidence of
      postoperative dislocation or deep vein thrombosis were found. CONCLUSIONS: The
      present meta-analysis indicated that the use of computer navigation in patients
      undergoing THA improves the precision of acetabular cup placement by decreasing
      the number of outliers, and decreases leg length discrepancy. More high quality
      RCTs are required to further confirm our results.

PMID- 24583366
TI  - Do mast cells play a pathogenetic role in neurofibromatosis type 1 and ulcerative
      colitis?
AB  - Concurrent association of neurofibromatosis type I and ulcerative colitis has
      been reported in one clinical case (Tavakkoli et al., 2009). Although this
      association may represent a casual finding, a common pathophysiology is
      postulated. Mast cells have been implicated in the pathogenesis of both
      neurofibromatosis type 1 and ulcerative colitis (He, 2004; Yoshida et al., 2010).
      Mast cells are typically present in neurofibromas microenvironment where they
      appear to contribute to tumor initiation, progression and angiogenesis (Staser et
      al., 2010, 2013). Moreover, interaction of mast cells with nerves throughout the
      gastrointestinal tract has been correlated with progression and maintenance of
      ulcerative colitis (Stoyanova and Gulubova, 2002). We describe a 14 year-old male
      with history of neurofibromatosis type 1 and new onset of ulcerative colitis
      diagnosed on clinical and histological findings. On gross examination the entire
      colonic mucosa appeared edematous showing a peculiar granular pattern, with focal
      erythema, shallow ulcers and multiple sessile polyps. Hematoxylin and eosin
      stained tissue biopsies from the colonic mucosa showed chronic inflammatory bowel
      disease, severe activity, consistent with chronic ulcerative colitis.
      Immunohistochemistry stain of the intestinal lesions revealed high expression of
      Neuron Specific Enolase (NSE) and S100 highlighting the presence of a Schwann
      cell component. In addition, c-kit/CD117 positive stain indicated a marked
      increase of mast cells in the lamina propria. This pattern of cellularity in the
      lamina propria showing increased mast cells and augmented Schwann cell component
      was absent in the colonic mucosa of a normal control or a patient with ulcerative
      colitis alone. Our observation supports the evidence of a pathogenetic role of
      the mast cell in ulcerative colitis associated with neurofibromatosis type 1.
      Further investigations are warranted to confirm the significance of this
      correlation as it may impact therapeutic approaches of these pathologies.

PMID- 24583367
TI  - Two basic (hydrophilic) regions in the movement protein of Parietaria mottle
      virus have RNA binding activity and are required for cell-to-cell transport.
AB  - The movement protein (MP) of parietaria mottle virus (PMoV) is required for virus
      cell-to-cell movement. Bioinformatics analysis identified two hydrophilic non
      contiguous regions (R1 and R2) rich in the basic amino acids lysine and arginine
      and with the predicted secondary structure of an alpha-helix. Different
      approaches were used to determine the implication of the R1 and R2 regions in RNA
      binding, plasmodesmata (PD) targeting and cell-to-cell movement. EMSA
      (Electrophoretic Mobility Shift Assay) showed that both regions have RNA-binding
      activity whereas that mutational analysis reported that either deletion of any of
      these regions, or loss of the basic amino acids, interfered with the viral
      intercellular movement. Subcellular localization studies showed that PMoV MP
      locates at PD. Mutants designed to impeded cell-to-cell movement failed to
      accumulate at PD indicating that basic residues in both R1 and R2 are critical
      for binding the MP at PD. 

PMID- 24583368
TI  - Bombyx mori nucleopolyhedrovirus ORF79 is a per os infectivity factor associated
      with the PIF complex.
AB  - Bombyx mori nucleopolyhedrovirus (BmNPV) ORF79 (Bm79) encodes an occlusion
      derived virus (ODV)-specific envelope protein, which is a homologue of the per os
      infectivity factor 4 (PIF4) of Autographa californica multiple
      nucleopolyhedrovirus (AcMNPV). To investigate the role of ORF79 in the BmNPV life
      cycle, a Bm79 knockout virus (vBm(Bm79KO)) was constructed through homologous
      recombination in Escherichia coli. Viral DNA replication, budded virus (BV)
      production and polyhedra formation were unaffected by the absence of BM79.
      However, results of the larval bioassay demonstrated that the Bm79 deletion
      resulted in a complete loss of per os infection. Immunofluorescence analysis
      showed that BM79 localized at the innernuclear membrane of infected cells through
      its N-terminal sorting motif (SM). Further bimolecular fluorescence protein
      complementation and co-immunoprecipitation assays demonstrated the interaction of
      BM79 with PIF1, PIF2, PIF3 and ODV-E66. Thus, BM79 plays an important role in per
      os infection and is associated with the viral PIF complex of BmNPV. 

PMID- 24583369
TI  - Effects of copper ions on DNA binding and cytotoxic activity of a chiral
      salicylidene Schiff base.
AB  - A chiral Schiff base HL N-(5-bromo-salicylaldehyde)dehydroabietylamine (1) and
      its chiral dinuclear copper complex [Cu2L4].4DMF (2) have been synthesized and
      fully characterized. The interactions of 1 and 2 with salmon sperm DNA have been
      investigated by viscosity measurements, UV, fluorescence and circular dichroism
      (CD) spectroscopic techniques. Absorption spectral (Kb=3.30 * 10(5)M(-)(1) (1),
      6.63 * 10(5)M(-)(1)(2)), emission spectral (Ksv=7.58 * 10(3)M(-)(1) (1), 1.52 *
      10(4)M(-)(1) (2)), and viscosity measurements reveal that 1 and 2 interact with
      DNA through intercalation and 2 exhibits a higher DNA binding ability. In
      addition, CD study indicates 2 cause a more evident perturbation on the base
      stacking and helicity of B-DNA upon binding to it. In fluorimetric studies, the
      enthalpy (DeltaH>0) and entropy (DeltaS>0) changes of the reactions between the
      compounds with DNA demonstrate hydrophobic interactions. 1 and 2 were also
      screened for their cytotoxic ability and 2 demonstrates higher growth inhibition
      of the selected cancer cells at concentration of 50 MUM, this result is identical
      with their DNA binding ability order. All the experimental results show that the
      involvement of Cu (II) centers has some interesting effect on DNA binding ability
      and cytotoxicity of the chiral Schiff base.

PMID- 24583371
TI  - Basolateral amygdala activity is required for enhancement of memory consolidation
      produced by histone deacetylase inhibition in the hippocampus.
AB  - Histone acetylation, a type of chromatin modification that allows increased gene
      transcription and can be pharmacologically promoted by histone deacetylase (HDAC)
      inhibitors (HDACis), has been consistently associated with promoting memory
      formation in the hippocampus. The basolateral nucleus of the amygdala (BLA) is a
      brain area crucially involved in enabling hormones and drugs to influence memory
      formation. Here, we show that BLA activity is required for memory enhancement by
      intrahippocampal administration of an HDACi. Two different HDACis, sodium
      butyrate (NaB) and trichostatin A (TSA), differentially enhanced the retention of
      memory for inhibitory avoidance (IA) when administered to the dorsal hippocampus
      after training. TSA showed a biphasic pattern of response during consolidation,
      in which infusions given immediately or 3h after training produced memory
      enhancement, whereas no effect was observed when it was infused 1.5 or 6h
      posttraining. Muscimol (MUS)-induced unilateral functional inactivation of the
      BLA prevented the enhancement of memory retention produced by posttraining
      infusion of TSA into the ipsilateral hippocampus. TSA did not affect IA
      extinction or reconsolidation. These results indicate that HDACis can increase IA
      memory retention when given into the hippocampus, and, most importantly, BLA
      activity is necessary for enabling HDACi-induced influences on memory formation. 

PMID- 24583370
TI  - Intraarterial injection of indocyanine green for evaluation of peripheral blood
      circulation in patients with peripheral arterial disease.
AB  - BACKGROUND: To assess the peripheral blood flow of patients with peripheral
      arterial disease (PAD) by indocyanine green (ICG) arteriography (ICGA) with
      intraarterial injection of ICG and evaluate the efficacy of the ICGA tests.
      METHODS: This study was undertaken from a retrospective review of patients with
      PAD who underwent ICGA tests during digital subtraction angiography (DSA) between
      November 2012 and June 2013. We defined some ICGA parameters as the magnitude of
      intensity of ICG, the time to maximum intensity, and the time from fluorescence
      onset to half the maximum intensity (T1/2). The ICGA parameters were evaluated in
      2 regions, named regions of interest (ROIs). ROI 1 was part of the dorsum of the
      foot from the Chopart joint to the Lisfranc joint. ROI 2 was in the distal region
      of the first metatarsal bone and compared with the ankle-brachial pressure index
      (ABI), ankle pressure, toe-brachial pressure index, and toe pressure. RESULTS: A
      total of 22 limbs in 16 patients with PAD underwent ICGA tests during DSA. The
      T1/2 on ROI 2 was the most correlated with the ABI (rho=-0.622, P=0.003). A value
      of T1/2 for ROI 2>10 sec was significantly correlated with an ABI value of <0.7
      (sensitivity: 0.85, specificity: 1.0). CONCLUSIONS: By measuring the value of
      T1/2 in ROI 2, ICGA tests can be performed to assess the peripheral blood
      circulation during DSA. ICGA tests might help to promptly assess the peripheral
      blood flow during endovascular treatment procedures.

PMID- 24583373
TI  - How the amygdala affects emotional memory by altering brain network properties.
AB  - The amygdala has long been known to play a key role in supporting memory for
      emotionally arousing experiences. For example, classical fear conditioning
      depends on neural plasticity within this anterior medial temporal lobe region.
      Beneficial effects of emotional arousal on memory, however, are not restricted to
      simple associative learning. Our recollection of emotional experiences often
      includes rich representations of, e.g., spatiotemporal context, visceral states,
      and stimulus-response associations. Critically, such memory features are known to
      bear heavily on regions elsewhere in the brain. These observations led to the
      modulation account of amygdala function, which postulates that amygdala
      activation enhances memory consolidation by facilitating neural plasticity and
      information storage processes in its target regions. Rodent work in past decades
      has identified the most important brain regions and neurochemical processes
      involved in these modulatory actions, and neuropsychological and neuroimaging
      work in humans has produced a large body of convergent data. Importantly, recent
      methodological developments make it increasingly realistic to monitor neural
      interactions underlying such modulatory effects as they unfold. For instance,
      functional connectivity network modeling in humans has demonstrated how
      information exchanges between the amygdala and specific target regions occur
      within the context of large-scale neural network interactions. Furthermore,
      electrophysiological and optogenetic techniques in rodents are beginning to make
      it possible to quantify and even manipulate such interactions with millisecond
      precision. In this paper we will discuss that these developments will likely lead
      to an updated view of the amygdala as a critical nexus within large-scale
      networks supporting different aspects of memory processing for emotionally
      arousing experiences. 

PMID- 24583372
TI  - Altered hippocampal function before emotional trauma in rats susceptible to PTSD
      like behaviors.
AB  - Posttraumatic stress disorder (PTSD) is an anxiety disorder that occurs after
      experiencing a traumatic event. Susceptibility to PTSD exists, as only some
      trauma-exposed individuals develop this condition. Investigating susceptibilities
      in animal models can contribute to understanding the etiology of the disorder. We
      previously reported an animal model which allows reliable pre-classification of
      rats as susceptible (Sus) or resistant (Res) to developing a PTSD-like phenotype
      after a later trauma. Here we report that Sus, compared to Res, rats have altered
      hippocampal function, along the septo-temporal axis, prior to experiencing a
      traumatic event. In Experiment I, Res and Sus rats explored a novel box twice.
      Using a cellular imaging method for assessing plasticity-related immediate-early
      gene expression in large neuronal ensembles, Arc/Homer1a catFISH, we show that
      Sus rats have smaller vCA3 ensembles during the second exploration. This
      suppressed vCA3 activation in Sus rats was not due to a difference in exploratory
      behavior, or to a difference in Arc/Homer1a expression in the basolateral
      amygdala (BLA). BLA is a main source of inputs to vCA3, but both the ensemble
      size and overlap of BLA ensembles activated during the two explorations was
      similar to that of Res rats. Additionally, Sus rats had significant 'infidelity'
      in their dorsal hippocampal representations of the second event: a lower overlap,
      compared to Res rats, of Arc/Homer1a-expressing ensembles activated during the
      two explorations (the size of the ensembles were similar to those of Res rats).
      These differences were revealed only in conditions of relatively low stress,
      because they were not observed when Sus and Res rats experienced fear
      conditioning (Experiment II). Combined, the findings show that altered
      hippocampal function exists before experiencing emotional trauma in susceptible
      rats and suggest that this is a risk factor for PTSD. 

PMID- 24583375
TI  - Phosphatidylcholine metabolism and choline kinase in human osteoblasts.
AB  - There is a paucity of information about phosphatidylcholine (PC) biosynthesis in
      bone formation. Thus, we characterized PC metabolism in both primary human
      osteoblasts (HOB) and human osteosarcoma MG-63 cells. Our results show that the
      CDP-choline pathway is the only de novo route for PC biosynthesis in both HOB and
      MG-63 cells. Both CK activity and CKalpha expression in MG-63 cells were
      significantly higher than those in HOB cells. Silencing of CKalpha in MG-63 cells
      had no significant effect on PC concentration but decreased the amount of
      phosphocholine by approximately 80%. The silencing of CKalpha also reduced cell
      proliferation. Moreover, pharmacological inhibition of CK activity impaired the
      mineralization capacity of MG-63 cells. Our data suggest that CK and its product
      phosphocholine are required for the normal growth and mineralization of MG-63
      cells. 

PMID- 24583374
TI  - Extinction in multiple virtual reality contexts diminishes fear reinstatement in
      humans.
AB  - Although conditioned fear can be effectively extinguished by unreinforced
      exposure to a threat cue, fear responses tend to return when the cue is
      encountered some time after extinction (spontaneous recovery), in a novel
      environment (renewal), or following presentation of an aversive stimulus
      (reinstatement). As extinction represents a context-dependent form of new
      learning, one possible strategy to circumvent the return of fear is to conduct
      extinction across several environments. Here, we tested the effectiveness of
      multiple context extinction in a two-day fear conditioning experiment using 3-D
      virtual reality technology to create immersive, ecologically-valid context
      changes. Fear-potentiated startle served as the dependent measure. All three
      experimental groups initially acquired fear in a single context. A multiple
      extinction group then underwent extinction in three contexts, while a second
      group underwent extinction in the acquisition context and a third group underwent
      extinction in a single different context. All groups returned 24h later to test
      for return of fear in the extinction context (spontaneous recovery) and a novel
      context (renewal and reinstatement/test). Extinction in multiple contexts
      attenuated reinstatement of fear but did not reduce spontaneous recovery. Results
      from fear renewal were tendential. Our findings suggest that multi-context
      extinction can reduce fear relapse following an aversive event--an event that
      often induces return of fear in real-world settings--and provides empirical
      support for conducting exposure-based clinical treatments across a variety of
      environments.

PMID- 24583376
TI  - Gene and cell therapy for children--new medicines, new challenges?
AB  - The range of possible gene and cell therapy applications is expanding at an
      extremely rapid rate and advanced therapy medicinal products (ATMPs) are
      currently the hottest topic in novel medicines, particularly for inherited
      diseases. Paediatric patients stand to gain enormously from these novel therapies
      as it now seems plausible to develop a gene or cell therapy for a vast number of
      inherited diseases. There are a wide variety of potential gene and cell therapies
      in various stages of development. Patients who received first gene therapy
      treatments for primary immune deficiencies (PIDs) are reaching 10 and 15 years
      post-treatment, with robust and sustained immune recovery. Cell therapy clinical
      trials are underway for a variety of tissues including corneal, retinal and
      muscle repair and islet cell transplantation. Various cell therapy approaches are
      also being trialled to enhance the safety of bone marrow transplants, which
      should improve survival rates in childhood cancers and PIDs. Progress in genetic
      engineering of lymphocyte populations to target and kill cancerous cells is also
      described. If successful these ATMPs may enhance or replace the existing chemo
      ablative therapy for several paediatric cancers. Emerging applications of gene
      therapy now include skin and neurological disorders such as epidermolysis
      bullosa, epilepsy and leukodystrophy. Gene therapy trials for haemophilia,
      muscular dystrophy and a range of metabolic disorders are underway. There is a
      vast array of potential advanced therapy medicinal products (ATMPs), and these
      are likely to be more cost effective than existing medicines. However, the first
      clinical trials have not been without setbacks and some of the key adverse events
      are discussed. Furthermore, the arrival of this novel class of therapies brings
      many new challenges for the healthcare industry. We present a summary of the key
      non-clinical factors required for successful delivery of these potential
      treatments. Technological advances are needed in vector design, raw material
      manufacture, cell culture and transduction methodology, and particularly in
      making all these technologies readily scalable.

PMID- 24583377
TI  - Regression discontinuity design in criminal justice evaluation: an introduction
      and illustration.
AB  - BACKGROUND: Corrections agencies frequently place offenders into risk categories,
      within which offenders receive different levels of supervision and programming.
      This supervision strategy is seldom evaluated but often can be through routine
      use of a regression discontinuity design (RDD). This article argues that RDD
      provides a rigorous and cost-effective method for correctional agencies to
      evaluate and improve supervision strategies and advocates for using RDD routinely
      in corrections administration. The objective is to better employ correctional
      resources. METHOD: This article uses a Neyman-Pearson counterfactual framework to
      introduce readers to RDD, to provide intuition for why RDD should be used
      broadly, and to motivate a deeper reading into the methodology. The article also
      illustrates an application of RDD to evaluate an intensive supervision program
      for probationers. RESULT: Application of the RDD, which requires basic knowledge
      of regressions and some special diagnostic tools, is within the competencies of
      many criminal justice evaluators. RDD is shown to be an effective strategy to
      identify the treatment effect in a community corrections agency using supervision
      that meets the necessary conditions for RDD. CONCLUSION: The article concludes
      with a critical review of how RDD compares to experimental methods to answer
      policy questions. The article recommends using RDD to evaluate whether differing
      levels of control and correction reduce criminal recidivism. It also advocates
      for routine use of RDD as an administrative tool to determine cut points used to
      assign offenders into different risk categories based on the offenders' risk
      scores.

PMID- 24583378
TI  - Novel mixed ligand di-n-butyltin(IV) complexes derived from acylpyrazolones and
      fluorinated benzoic acids: synthesis, characterization, cytotoxicity and the
      induction of apoptosis in Hela cancer cells.
AB  - Twenty one novel mixed ligand di-n-butyltin(IV) complexes [(n)Bu2SnAL] (A =
      substituted 4-acyl-5-pyrazolone, and L = fluorinated benzoic acid) were prepared
      by condensation of di-n-butyltin(IV) oxide with HL and HA in 1:1:1 molar ratio in
      refluxing methanol. All of the complexes were characterized by elemental
      analyses, IR, NMR ((1)H, (13)C, (119)Sn) and in four cases by X-ray diffraction.
      Cytotoxicity of the compounds was studied against two human cancer cell lines (KB
      and Hela) by means of the MTT assay compared to cisplatin, featuring IC50 values
      in the low micromolar range. Hela cancer cell apoptosis-induced by 2 was examined
      by flow cytometry analysis, and preliminary results showed that 2 at
      concentrations of more than 1.0 MUM can induce apoptosis.

PMID- 24583379
TI  - Discovery of novel urea derivatives as dual-target hypoglycemic agents that
      activate glucokinase and PPARgamma.
AB  - Motivated by the discovery of a potential ligand that activates both glucokinase
      (GK) and perioxisome proliferator-activated receptor-gamma (PPARgamma), this work
      presents the rational design and synthesis of a series of novel urea derivatives
      as potent dual-target ligands of GK and PPARgamma. The derivatives obtained,
      particularly compounds 14j, 14m, 15g, 15j, and 15s, showed relatively high enzyme
      activity and moderate blood glucose-lowering efficacy in normal ICR mice (GK
      activation fold >1.7, PPARgamma activation percentage >38.8%, relative to
      rosiglitazone). The discovery of a dual-acting agent may provide an effective
      approach for treating type 2 diabetes mellitus. 

PMID- 24583380
TI  - Milk proteins-derived bioactive peptides in dairy products: molecular, biological
      and methodological aspects.
AB  - Proteins are one of the primary components of the food, both in terms of
      nutrition and function. They are main source of amino acids, essential for
      synthesis of proteins, and also source of energy. Additionally, many proteins
      exhibit specific biological activities, which may have effect on functional or
      pro-health properties of food products. These proteins and their hydrolysis
      products, peptides, may influence the properties of food and human organism. The
      number of commercially available food products containing bioactive peptides is
      very low, apart from that milk proteins are their rich source. It could be
      supposed that number of available products with declared activity will rise in
      near future because of observed strong uptrend on interest in such products.
      Molecular and biological properties of milk proteins, as precursors of bioactive
      peptides was characterised in the work. Therefore, the strategy of research and
      obtaining of such peptides both in laboratory and industrial scale, as well as
      the range of their commercial application, was presented. Several examples of
      research efforts presenting high potential to develop new products containing
      bioactive peptides from milk proteins and predetermined as nutraceuticals was
      described.

PMID- 24583381
TI  - Fortification of white flat bread with sprouted red kidney bean (Phaseolus
      vulgaris).
AB  - BACKGROUND: Protein quantity in diet including the digestibility and
      bioavailability of protein is of importance to eradicate undernutrition in
      developing countries. Bread protein is an incomplete source as it lacks an
      essential amino acid lysine. When they are combined with other plant foods like
      pulses and legumes, they become a complete source of protein. Since bread is most
      common staple food the objective of this study is to fortify bread with legumes
      in order to increase the total protein content of bread to 13-15% which is
      required to meet at least 1/3rd of protein requirement of an adult recommended
      daily allowance. MATERIAL AND METHODS: Fortification of flat bread was done by
      adding sprouted red kidney bean flour (Phaseolus vulgaris) at 5, 15 and 25% to
      white flour. The composite bread was analysed for crude protein and in vitro
      protein digestibility using the Kjeldahl and pepsin-pancreatin method. RESULTS:
      The protein content of raw beans showed trivial increase on soaking for 17 h and
      sprouting for 3 days. On the other hand, a remarkable increase was observed in
      protein digestibility i.e., 8% and 11% respectively. The protein content of
      control and composite breads increased gradually at 1% and protein digestibility
      decreased by 12% from control. This is due to the presence of dietary fibers
      which bind with protein and inhibit its digestibility. CONCLUSION: The study
      infers that sprouting the beans for 72 h did not show any remarkable increase in
      protein content but a significant increase in in vitro protein digestibility was
      observed. Overall, breads made using 15% legume flour was comparatively equal in
      protein content, with overall acceptable quality.

PMID- 24583382
TI  - Yoghurts with addition of selected vegetables: acidity, antioxidant properties
      and sensory quality.
AB  - BACKGROUND: Yoghurt is a fermented milk of unique sensory, nutritive and dietetic
      value offered in a variety of types and in different flavours. Vegetables belong
      to the group of food products rich in antioxidant substances (e.g., vitamin C,
      carotenoids, tocopherols, polyphenols) which regular consumption lowers the risk
      of many diseases including cancers and cardiovascular disorders. The aim of the
      present work was to manufacture and assess the acidity, sensory quality and
      antioxidant capacity of yoghurts with addition of selected vegetables during 2
      week refrigerated storage. MATERIAL AND METHODS: The vegetable preparations
      (carrot, pumpkin, broccoli and red sweet pepper) were added to the cow's milk
      fermented using DVS type yoghurt culture after initial cooling to 15-20 degrees C
      in the amount of 10% (w/w). The following analyses were performed: determination
      of pH, titratable acidity, antioxidant activity by ferric reducing antioxidant
      power (FRAP) and 2,2'-diphenyl-1-picrylhydrazyl (DPPH) method as well as sensory
      evaluation and were conducted after 1, 7 and 14 days of cold storage. RESULTS:
      The yoghurt supplementation with selected vegetables had no significant effect on
      the pH and titratable acidity level. The highest ability to scavenge DPPH
      radicals was stated for yoghurts with broccoli and red sweet pepper. The latter
      treatment gained the highest notes in sensory evaluation. All vegetable yoghurts
      were characterised by higher than the natural yoghurt FRAP values measured
      directly after production. However, the level of this parameter significantly
      decreased after storage. CONCLUSIONS: The red sweet pepper additive was the most
      beneficial regarding antioxidant properties and organoleptic acceptance of the
      studied yoghurts.

PMID- 24583383
TI  - An addition of sourdough and whey proteins affects the nutritional quality of
      wholemeal wheat bread.
AB  - BACKGROUND: Bread can be a good source of nutrients as well as non-nutrient
      compounds. This study was designed to assess the effect of adding of sourdough
      and whey proteins to wholemeal (WM) bread produced by bake-off technology on
      chemical composition and bioavailability of proteins, calcium, phosphorus,
      magnesium and iron content in Wistar rats. MATERIAL AND METHODS: Wholemeal breads
      were baked with using conventional or bake off technology. In breads chemical
      composition, selected minerals content, amino acid composition were measured.
      Five week-old Wistar rats (n = 30, male), were randomly divided into fi ve groups
      and fed with modified AIN-93G diets containing experimental breads. In animal
      study the nutritional value of breads' proteins and concentration of selected
      minerals in serum, liver and femoral bone, were measured. RESULTS: The body
      weight gain, biological value (BV) and net protein utilization (NPU) were
      significantly higher in rats fed with partially baked frozen wholemeal (PBF WM)
      bread with sourdough and whey proteins. The level of magnesium was significantly
      lower in serum of animals fed with the diet containing PBF WM bread with
      sourdough and whey proteins in comparison to rodents fed with conventional WM
      bread with sourdough. The content of iron was significantly higher in liver of
      rats fed with PBF WM with sourdough bread in comparison to the groups fed with
      conventional WM and conventional WM with sourdough breads. CONCLUSIONS: Sourdough
      addition can be recommended in a production of whole wheat partially baked frozen
      bread but its use is further more beneficial if it is fermented with whey
      proteins.

PMID- 24583384
TI  - Effect of lupine as cheese base substitution on technological and nutritional
      properties of processed cheese analogue.
AB  - BACKGROUND: Healthy foods have been met with marked success in the last two
      decades. Lupine flours, protein concentrates, and isolates can be applied as a
      substance for enriching different kinds of food systems such as bakery products,
      lupine pasta, ice cream, milk substitutes. Imitation processed cheese is made
      from mixtures of dairy and/or non dairy proteins and fat/oils and is variously
      labeled analogue, artificial, extruded, synthetic and/or filled. Processed cheese
      can be formulated using different types of cheese with different degree of
      maturation, flavorings, emulsifying, salts, and/or several ingredients of non
      dairy components. Non-dairy ingredients have been used in processed cheese for
      many dietary and economic reasons. In this study, lupine paste was used to
      substitute 25, 50, 75 and 100% of cheese in base formula of processed cheese
      analogue (PCA). MATERIAL AND METHODS: Matured Ras cheese (3 months old) was
      manufactured using fresh cow milk. Soft cheese curd was manufactured using fresh
      buffalo skim milk. Emulsifying salts S9s and Unsalted butter were used. Lupine
      termis paste was prepared by soaking the seeds in tap water for week with
      changing the water daily, and then boiled in water for 2 hrs, cooled and peeled.
      The peeled seeds were minced, blended to get very fine paste and kept frozen
      until used. RESULTS: Lupine paste was used to substitute 25, 50, 75 and 100% of
      cheese in base formula of processed cheese analogue (PCA). The obtained PCA were
      analysed when fresh and during storage up to 3 months at 5+/-2 degrees C for
      chemical composition, physical and sensory properties. The histopathological
      effect of lupines on alloxan diabetic albino rats and nutritional parameters were
      also investigated. Incorporation of lupine paste in PCA increased the ash and
      protein contents while meltability and penetration values of resultant products
      were decreased. Adding lupine in PSA formula had relatively increased the oil
      index and firmness of products. Feeding rats a balanced diet containing processed
      cheese enriched with lupine showed marked improvements in islets structure and
      lowered blood glucose compared to rats fed on basil diet (negative group).
      Springiness was greatly reduced with increasing the added ratio of lupine in the
      formula of cheese. All processed cheese produced were sensory acceptable but an
      overall acceptability was lowered by incorporating lupine in PCA formula. Body
      and texture score of PCA was the mostly affected by increasing lupine ratio in
      formula without significant difference up to 50% substitution of cheese base.

PMID- 24583385
TI  - Prediction of some physical and drying properties of terebinth fruit (Pistacia
      atlantica L.) using Artificial Neural Networks.
AB  - BACKGROUND: Drying of terebinth fruit was conducted to provide microbiological
      stability, reduce product deterioration due to chemical reactions, facilitate
      storage and lower transportation costs. Because terebinth fruit is susceptible to
      heat, the selection of a suitable drying technology is a challenging task.
      Artificial neural networks (ANNs) are used as a nonlinear mapping structures for
      modelling and prediction of some physical and drying properties of terebinth
      fruit. MATERIAL AND METHODS: Drying characteristics of terebinth fruit with an
      initial moisture content of 1.16 (d.b.) was studied in an infrared fluidized bed
      dryer. Different levels of air temperatures (40, 55 and 70 degrees C), air
      velocities (0.93, 1.76 and 2.6 m/s) and infrared (IR) radiation powers (500, 1000
      and 1500 W) were applied. In the present study, the application of Artificial
      Neural Network (ANN) for predicting the drying moisture diffusivity, energy
      consumption, shrinkage, drying rate and moisture ratio (output parameter for ANN
      modelling) was investigated. Air temperature, air velocity, IR radiation and
      drying time were considered as input parameters. RESULTS: The results revealed
      that to predict drying rate and moisture ratio a network with the TANSIG-LOGSIG
      TANSIG transfer function and Levenberg-Marquardt (LM) training algorithm made the
      most accurate predictions for the terebinth fruit drying. The best results for
      ANN at predications were R2 = 0.9678 for drying rate, R2 = 0.9945 for moisture
      ratio, R2 = 0.9857 for moisture diffusivity and R2 = 0.9893 for energy
      consumption. CONCLUSION: Results indicated that artificial neural network can be
      used as an alternative approach for modelling and predicting of terebinth fruit
      drying parameters with high correlation. Also ANN can be used in optimization of
      the process.

PMID- 24583386
TI  - Food and drug interactions: a general review.
AB  - Although it is well known and identified that drug-drug interactions exist, the
      recognition of importance of food and drug interactions to practice has been
      growing much slower. On the other hand, drug-food/nutrient interactions continue
      to grow with the common use of medications. Beside the awareness of this type of
      interactions, food-drug interaction studies are critical to evaluate appropriate
      dosing, timing, and formulation of new drug candidates. Drug-food interactions
      take place mechanistically due to altered intestinal transport and metabolism, or
      systemic distribution, metabolism and excretion. In addition, some people have
      greater risk of food and drug interactions who have a poor diet, have serious
      health problems, childrens and pregnant women. In this article, basic
      informations about importance, classifications, transporters and enzymes of drug
      and nutrient interaction are given and some specific examples of both drug and
      nutrients and influences on each other are included.

PMID- 24583387
TI  - Evaluation of nutritional and biochemical parameters in spontaneously
      hypertensive rats following antihypertensive treatment.
AB  - INTRODUCTION: One side effect of antihypertensive drugs is their impact on
      nutritional status and metabolism. The purpose of this study was to assess the
      nutritional and biochemical parameters in spontaneously hypertensive rats
      following treatment with antihypertensive drugs. MATERIAL AND METHODS: The
      experiment was performed on 50 male spontaneously hypertensive rats (SHR), which
      were assigned to five groups: control (C), with perindopril (PR), with metoprolol
      (MT), with indapamide (ID), and with amlodipine (AM). All rats were provided ad
      libitum standard diet (with or without drugs) and distilled water. After 45 days,
      the animals were weighed and killed. Liver, kidney, heart, spleen, pancreas, and
      blood samples were collected. Concentrations of glucose, cholesterol,
      triglycerides, and albumin were assayed in serum. Morphology parameters, such as
      white blood cell, red blood cell, hematocrit, and lymphocyte counts were measured
      in the blood. Blood pressure was measured using a tail-cuff plethysmograph.
      RESULTS: The results obtained indicate that the hypotensive drugs under
      investigation had no effect on the selected nutritional parameters. Perindopril
      significantly decreased the relative mass of the heart and amlodipine markedly
      decreased the relative mass of the pancreas. A markedly higher concentration of
      glucose in the group with indapamid, and a significantly lower concentration of
      triglycerides in the group with metoprolol, were observed. Indapamide and
      amlodipine markedly increased the value of red blood cells and hematocrit in the
      blood of SHR. CONCLUSIONS: Long-term therapy with antihypertension drugs may
      influence tissue mass and biochemical and morphological status in the body.

PMID- 24583388
TI  - Polyunsaturated fatty acids and not plant sterols naturally-occurring in food
      influence lipid profile in obese women.
AB  - BACKGROUND: The aim of this study was to assess the influence of the consumption
      level of plant sterols naturally occurring in diet on the lipid profile in obese
      women with dyslipidemia. MATERIAL AND METHODS: The study population was primarily
      comprised of 120 obese women aged over 55 from Poland, with twenty seven subjects
      dropping out of the study due to the inclusion and exclusion criteria.
      Anthropometric appraisal included body height and weight, as well as waist and
      hip circumferences. Lipid profile was determined by commercially available
      enzymatic methods. Nutritional data, including plant sterols intake were assessed
      by 7-day food records. RESULTS: The multiple linear regression, adjusted for age,
      height, Body Mass Index and Waist to Hip Ratio, showed the relation of
      polyunsaturated fatty acids with LDL-cholesterol concentration (p < 0.05).
      Natural plant sterols intake was estimated at Median = 146 mg/day. The
      correlation between LDL-cholesterol concentration and plant sterols intake was
      not statistically significant (p > 0.05). CONCLUSIONS: The results of this study
      suggest that consumption of naturally-occurring polyunsaturated fatty acids and
      not plant sterols is connected with lower LDL-cholesterol concentration in obese
      women.

PMID- 24583389
TI  - Temporal trends (1999-2010) of perfluoroalkyl acids in commonly consumed food
      items.
AB  - The aim of this study was to determine how dietary exposure to PFAAs has changed
      over the period when major production changes occurred. Archived samples (1999
      2010) of eggs, milk and farmed rainbow trout were analyzed by ultra performance
      liquid chromatography coupled to tandem mass spectrometry. Statistically
      significant decreasing trends were observed for concentrations of perfluorooctane
      sulfonic acid (PFOS) and perfluorohexane sulfonic acid (PFHxS) in fish (p < 0.002
      and p < 0.032, respectively) and eggs (p < 0.001 for both compounds).
      Concentrations of PFOS in fish and eggs decreased by a factor of 10 and 40,
      respectively. In eggs there was also a statistically significant decreasing trend
      in concentrations of perfluorooctanoic acid (PFOA). The results of this study
      demonstrate that PFAA concentrations in food items from agricultural food chains
      and aquatic food chains close to sources respond rapidly to changes in
      environmental emissions. Implications for the overall understanding of human
      exposure are discussed. 

PMID- 24583390
TI  - Partitioning of magnetic particles in PM10, PM2.5 and PM1 aerosols in the urban
      atmosphere of Barcelona (Spain).
AB  - A combined magnetic-chemical study of 15 daily, simultaneous PM10-PM2.5-PM1 urban
      background aerosol samples has been carried out. The magnetic properties are
      dominated by non-stoichiometric magnetite, with highest concentrations seen in
      PM10. Low temperature magnetic analyses showed that the superparamagnetic
      fraction is more abundant when coarse, multidomain particles are present,
      confirming that they may occur as an oxidized outer shell around coarser grains.
      A strong association of the magnetic parameters with a vehicular PM10 source has
      been identified. Strong correlations found with Cu and Sb suggests that this
      association is related to brake abrasion emissions rather than exhaust emissions.
      For PM1 the magnetic remanence parameters are more strongly associated with
      crustal sources. Two crustal sources are identified in PM1, one of which is of
      North African origin. The magnetic particles are related to this source and so
      may be used to distinguish North African dust from other sources in PM1. 

PMID- 24583391
TI  - Organohalogen contamination in passerine birds from three metropolises in China:
      geographical variation and its implication for anthropogenic effects on urban
      environments.
AB  - Contamination of organohalogen pollutants (OHPs), including dichlorodiphenyl
      trichloroethane and its metabolites (DDTs), polychlorinated biphenyls (PCBs),
      polybrominated diphenyl ethers (PBDEs), decabromodiphenylethane (DBDPE),
      hexabromocyclododecanes (HBCDs), and dechlorane plus (DP) in three metropolises
      of China, Beijing, Wuhan, and Guangzhou, and a reference rural site were
      determined using terrestrial residential passerine species as bioindicator. DDTs
      dominated in Wuhan whereas flame retardants dominated in Guangzhou and Beijing.
      No geographical variation was found for PCB levels but it exhibited different
      homologue profiles among different sites which could be attributed to different
      dietary sources of birds. Industry characteristics of the sampling location
      contributed to the geographical differences in the occurrence and contamination
      profile of OHPs. The transformation of traditional agriculture characterized
      contamination profiles to industry characterized profiles in Beijing and
      Guangzhou implicates significantly environmental concern on the flame retardants
      contamination in non-hot-spot regions of China. 

PMID- 24583392
TI  - Genomes in the clinic: the Gustave Roussy Cancer Center experience.
AB  - The extensive molecular characterization of tumors with high throughput
      technologies has led to the segmentation of different tumors into very small
      molecularly defined subgroups. Many ongoing clinical trials are conducted only
      when specific molecular alterations are identified in tumor samples. In this
      review, we will describe the implementation of genome analysis in the clinical
      setting as it has expanded over the last four years in our Precision Medicine
      Program. This manuscript will also highlight the main limitations and challenges
      related to the development of broader and deeper genome analysis. 

PMID- 24583394
TI  - Enhanced carrier extraction of a-Si/c-Si solar cells by nanopillar-induced
      optical modulation.
AB  - We demonstrate improved short-wavelength internal quantum efficiency (IQE) of a
      Si/c-Si heterojunction (HJ) solar cells with a surface nanopillar (NP) array via
      simulation. The gain in IQE is attributed to the light-field modulation caused by
      the cavity resonance inside the NPs, in which the light energy is effectively
      localized within the c-Si bulk rather than the a-Si layer. The average IQE in the
      short-wavelength range (330-450 nm) is enhanced from 43.94% to 62.88% by the
      optimal NP array, with a maximum IQE of 80.98% at lambda = 400 nm. The resulting
      current gain is over 38.25% compared to a planar HJ cell in this wavelength
      range, showing a well suppressed recombination-induced current loss. This light
      management scheme may also find applications in other types of cells.

PMID- 24583393
TI  - Replicative DNA polymerase mutations in cancer.
AB  - Three DNA polymerases - Pol alpha, Pol delta and Pol E - are essential for DNA
      replication. After initiation of DNA synthesis by Pol alpha, Pol delta or Pol E
      take over on the lagging and leading strand respectively. Pol delta and Pol E
      perform the bulk of replication with very high fidelity, which is ensured by
      Watson-Crick base pairing and 3'exonuclease (proofreading) activity. Yeast models
      have shown that mutations in the exonuclease domain of Pol delta and Pol E
      homologues can cause a mutator phenotype. Recently, we identified germline
      exonuclease domain mutations (EDMs) in human POLD1 and POLE that predispose to
      'polymerase proofreading associated polyposis' (PPAP), a disease characterised by
      multiple colorectal adenomas and carcinoma, with high penetrance and dominant
      inheritance. Moreover, somatic EDMs in POLE have also been found in sporadic
      colorectal and endometrial cancers. Tumors with EDMs are microsatellite stable
      and show an 'ultramutator' phenotype, with a dramatic increase in base
      substitutions. 

PMID- 24583395
TI  - KDM5C mutational screening among males with intellectual disability suggestive of
      X-Linked inheritance and review of the literature.
AB  - An increasing number of neurodevelopmental diseases have been associated with
      disruption of chromatin remodeling in eukaryotes. Lysine(K)-specific demethylase
      5C (KDM5C) is a versatile epigenetic regulator that removes di- and tri-methyl
      groups of lysine 4 on histone H3 (H3K4) from transcriptional targets and is
      essential for neuronal survival and dendritic growth. Mutations in KDM5C gene,
      located at Xp11.22, have been reported as an important cause of both syndromic
      and non-syndromic X-linked intellectual disability (XLID) in males. The aim of
      this study was to evaluate the prevalence and spectrum of KDM5C mutations among
      Brazilian patients with XLID. To access the impact of KDM5C variants on XLID, a
      cohort of 143 males with a family history of intellectual disability (ID)
      suggestive of X-linked inheritance were enrolled. Common genetic causes of XLID
      were previously excluded and the entire coding and flanking intronic sequences of
      KDM5C gene were screened by direct Sanger sequencing. Seven nucleotide changes
      were observed: one pathogenic mutation (c.2172C>A, p.Cys724*), one novel variant
      with unknown value (c.633G>C, p.Arg211Arg) and five apparently benign sequence
      changes. In silico analysis of the variants revealed a putative creation of an
      Exonic Splicing Enhancer sequence by the silent c.633G>C mutation, which co
      segregates with the ID phenotype. Our results point out to a KDM5C pathogenic
      mutational frequency of 0.7% among males with probable XLID. This is the first
      KDM5C screening among ID males from a country in Latin America and provides new
      clues about the significance of KDM5C mutations for genetic counseling. 

PMID- 24583396
TI  - The effect of catalase on migration and invasion of lung cancer cells by
      regulating the activities of cathepsin S, L, and K.
AB  - Abundant clinical evidences indicate that up-regulation of several cathepsins in
      many human cancers is correlated with malignant progression and poor patient
      prognosis. In addition, a decrease in catalase activity or accumulation of
      hydrogen peroxide correlates with cancer metastasis. Recent studies indicate that
      cathepsin activation and expression can be modulated via H2O2 treatment. However,
      the actual relationship between catalase and cathepsins is not yet fully
      understood. In the present study, we found that catalase expression (or activity)
      was higher, while intracellular and extracellular Cat S, Cat L, and Cat K
      activities were lower in the non-invasive CL1-0 cells compared to the highly
      invasive CL1-5 cells. After CL1-0 cells were transfected with catalase-shRNA, the
      corresponding ROS (H2O2) level and Cat S, Cat L, or Cat K expression (or
      activity) was up-regulated, accompanied by an increase in cell migration and
      invasion. On the other hand, ROS (H2O2) level, cathepsin S, L, and K activities,
      cell migration and invasion were decreased in catalase-overexpressed CL1-5 cells.
      It is suggested that catalase may regulate cathepsin activity by controlling the
      production of ROS (H2O2), leading to variation in migration and invasion ability
      of lung cancer cells. 

PMID- 24583398
TI  - Redox regulation of MMP-3/TIMP-1 ratio in intestinal myofibroblasts: effect of N
      acetylcysteine and curcumin.
AB  - Matrix metalloproteinases (MMPs) play a critical role in inflammation and
      ulcerations in gut of Crohn's disease (CD) patients. Intestinal subepithelial
      myofibroblasts (ISEMFs) secrete MMPs in response to inflammatory stimuli.
      Previous data showed in CD-ISEMFs increased oxidative status. The aim of this
      study was to investigate the role of ISEMFs in modulating the production of MMP-3
      and TIMP-1, an inhibitor of MMPs activity. A relationship among oxidative stress,
      activity of antioxidants and MMP-3/TIMP-1 was also studied. ISEMFs isolated from
      CD patient colon and human colonic cell line of myofibroblasts (18Co) were used.
      Oxidative state was modulated by buthionine sulfoximine, an inhibitor of
      glutathione (GSH) synthesis, and N-acetylcysteine (NAC), GSH precursor. An up
      regulation of MMP-3 due to increased oxidative state was found in CD-ISEMFs.
      Stimulation by tumor necrosis factor (TNF)alpha increased further MMP-3 levels.
      On the contrary, no change in TIMP-1 production was determined. NAC treatment
      decreased MMP-3 production in CD-ISMEFs and removed the enhancement due to
      TNFalpha. Similar effects were observed in 18Co cells treated with curcumin,
      antioxidant with anti-inflammatory properties. The involvement of MAPKs on MMP-3
      redox regulation was also shown. This study demonstrates the involvement of
      ISEMFs and high oxidative state in the increased MMP-3 production found in
      intestinal mucosa of CD patients. NAC and curcumin normalize MMP-3 levels mainly
      in TNFalpha stimulated cells. A modulation of MMP-3 production by NAC and
      curcumin due to their direct action on transcriptional factors has been also
      suggested. Therefore, they could have a therapeutic use for the prevention and
      treatment of fistulaes in CD. 

PMID- 24583397
TI  - Overexpression of FABP3 inhibits human bone marrow derived mesenchymal stem cell
      proliferation but enhances their survival in hypoxia.
AB  - Studying the proliferative ability of human bone marrow derived mesenchymal stem
      cells in hypoxic conditions can help us achieve the effective regeneration of
      ischemic injured myocardium. Cardiac-type fatty acid binding protein (FABP3) is a
      specific biomarker of muscle and heart tissue injury. This protein is purported
      to be involved in early myocardial development, adult myocardial tissue repair
      and responsible for the modulation of cell growth and proliferation. We have
      investigated the role of FABP3 in human bone marrow derived mesenchymal stem
      cells under ischemic conditions. MSCs from 12 donors were cultured either in
      standard normoxic or modified hypoxic conditions, and the differential expression
      of FABP3 was tested by quantitative (RT)PCR and western blot. We also established
      stable FABP3 expression in MSCs and searched for variation in cellular
      proliferation and differentiation bioprocesses affected by hypoxic conditions. We
      identified: (1) the FABP3 differential expression pattern in the MSCs under
      hypoxic conditions; (2) over-expression of FABP3 inhibited the growth and
      proliferation of the MSCs; however, improved their survival in low oxygen
      environments; (3) the cell growth factors and positive cell cycle regulation
      genes, such as PCNA, APC, CCNB1, CCNB2 and CDC6 were all down-regulated; while
      the key negative cell cycle regulation genes TP53, BRCA1, CASP3 and CDKN1A were
      significantly up-regulated in the cells with FABP3 overexpression. Our data
      suggested that FABP3 was up-regulated under hypoxia; also negatively regulated
      the cell metabolic process and the mitotic cell cycle. Overexpression of FABP3
      inhibited cell growth and proliferation via negative regulation of the cell cycle
      and down-regulation of cell growth factors, but enhances cell survival in hypoxic
      or ischemic conditions. 

PMID- 24583399
TI  - Involvement of androgen receptor and glucose-regulated protein 78 kDa in human
      hepatocarcinogenesis.
AB  - Previous studies demonstrated that androgen receptor (AR) is expressed in human
      hepatocellular carcinoma (HCC), one of the male-dominant diseases. Glucose
      regulated protein 78 kDa (GRP78/Bip), which has a role in cancer development, is
      one of the androgen response genes in prostate cell lines. The aim of this study
      was to investigate the impact of AR on endoplasmic reticulum (ER)-stress
      signaling in human hepatoma. AR and GRP78 expressions were examined in human
      liver tissue panels. Human hepatoma cells stably expressing short hairpin RNA
      targeting AR and cells over-expressing AR were generated. The expressions of ER
      stress molecules and AR were measured by real-time RT-PCR and Western blotting.
      The effect of AR on ER-stress responsive gene expression was examined by reporter
      assay. Strong positive correlation between AR mRNA and GRP78 mRNA was observed in
      stage I/II-HCCs. AR enhanced ER-stress responsive element activities and GRP78
      expression, and regulated ER-stress response in hepatocytes. Sorafenib strongly
      induced significant apoptosis in HepG2 cells by the inhibition of AR and
      inhibition of the downstream GRP78. AR seems a co-regulator of GRP78 especially
      in earlier-stage HCC. AR plays a critical role in controlling ER-stress,
      providing new therapeutic options against HCC.

PMID- 24583400
TI  - The phosphorylation status and cytoskeletal remodeling of striatal astrocytes
      treated with quinolinic acid.
AB  - Quinolinic acid (QUIN) is a glutamate agonist which markedly enhances the
      vulnerability of neural cells to excitotoxicity. QUIN is produced from the amino
      acid tryptophan through the kynurenine pathway (KP). Dysregulation of this
      pathway is associated with neurodegenerative conditions. In this study we treated
      striatal astrocytes in culture with QUIN and assayed the endogenous
      phosphorylating system associated with glial fibrillary acidic protein (GFAP) and
      vimentin as well as cytoskeletal remodeling. After 24h incubation with 100 uM
      QUIN, cells were exposed to (32)P-orthophosphate and/or protein kinase A (PKA),
      protein kinase dependent of Ca(2+)/calmodulin II (PKCaMII) or protein kinase C
      (PKC) inhibitors, H89 (20 MUM), KN93 (10 MUM) and staurosporin (10nM),
      respectively. Results showed that hyperphosphorylation was abrogated by PKA and
      PKC inhibitors but not by the PKCaMII inhibitor. The specific antagonists to
      ionotropic NMDA and non-NMDA (50 uM DL-AP5 and CNQX, respectively) glutamate
      receptors as well as to metabotropic glutamate receptor (mGLUR; 50 uM MCPG),
      mGLUR1 (100 uM MPEP) and mGLUR5 (10 uM 4C3HPG) prevented the hyperphosphorylation
      provoked by QUIN. Also, intra and extracellular Ca(2+) quelators (1mM EGTA; 10 uM
      BAPTA-AM, respectively) prevented QUIN-mediated effect, while Ca(2+) influx
      through voltage-dependent Ca(2+) channel type L (L-VDCC) (blocker: 10 uM
      verapamil) is not implicated in this effect. Morphological analysis showed
      dramatically altered actin cytoskeleton with concomitant change of morphology to
      fusiform and/or flattened cells with retracted cytoplasm and disruption of the
      GFAP meshwork, supporting misregulation of actin cytoskeleton. Both
      hyperphosphorylation and cytoskeletal remodeling were reversed 24h after QUIN
      removal. Astrocytes are highly plastic cells and the vulnerability of astrocyte
      cytoskeleton may have important implications for understanding the neurotoxicity
      of QUIN in neurodegenerative disorders.

PMID- 24583401
TI  - Instruments for assessing risk of bias and other methodological criteria of
      animal studies: omission of well-established methods.

PMID- 24583402
TI  - Ethics review as a catalyst for progress.
AB  - There are several points where ethical decision-making has become paralyzed and
      inefficient as the field of Alzheimer's disease study has advanced. The focus of
      this review is to highlight these points and several lines of research that can
      inform ethical decision-making. The goal is to identify barriers and to move
      toward solutions. Examples of other fields of study that can be particularly
      useful for innovative ways to study effective ethical decision-making include
      implementation science and neuroscience of decision-making, as well as
      therapeutic investigations of other domains such as the human biology and
      psychology. 

PMID- 24583403
TI  - Under reporting of dementia deaths on death certificates: a systematic review of
      population-based cohort studies.
AB  - The purpose of this review is to assess the extent to which dementia is omitted
      as a cause of death from the death certificates of patients with dementia. A
      systematic literature search was performed to identify population-based cohort
      studies in which all participants were examined or screened for symptoms of
      dementia with a validated instrument followed by confirmation of any suspected
      cases with a clinical examination (two-phase investigation). Data were extracted
      in a standardized manner and assessed through the Strengthening the Reporting of
      Observational Studies in Epidemiology (STROBE) initiative. Seven studies met the
      selection criteria. These were from the Americas (5 articles: 2 from Canada, 2
      from the US, and 1 from Brazil) and Europe (2 articles: 1 from the UK and 1 from
      Spain). Each met at least 83% of the STROBE criteria. The reporting of dementia
      on death certificates was poor in these 7 studies, ranging from 7.2%-41.8%.
      Respiratory or circulatory-related problems were the most frequently reported
      causes of death among people who were demented but who were not reported as
      demented on death certificates. The use of death certificates for studying
      dementia grossly underestimates the occurrence of dementia in the population. The
      poor reporting of dementia on these certificates suggests a lack of awareness of
      the importance of dementia as a cause of death among medical personnel. There is
      an urgent need to provide better education on the importance of codification of
      dementia on death certificates in order to minimize errors in epidemiological
      studies on dementia. 

PMID- 24583404
TI  - Relation between copper, lipid profile, and cognition in elderly Jordanians.
AB  - The purpose of the current study was to examine the association of serum copper
      and lipid concentrations with changes in cognitive function in elderly Jordanian
      individuals. The study population consisted of two groups: 52 dementia patients
      and 50 control subjects. All individuals were screened using the Mini-Mental
      State Examination and Clock Drawing Test. Serum copper and lipid profile were
      also assessed. Results were statistically evaluated at p < 0.05 level of
      significance. The dementia group had 10.1% higher copper level than control
      subjects that was not statistically significant. No significant differences could
      be found between the two groups in lipid profile levels. There was no significant
      correlation between serum copper, lipid profile, and cognitive decline in elderly
      Jordanians. Demographic variables indicated that educational level less than 12
      years and illiterate demonstrated a 3.29 fold (p = 0.026) and 6.29 fold (p =
      0.002) increase in risk of developing dementia, respectively. Coffee intake
      demonstrated a protective effect against cognitive decline with 6.25 fold lower
      risk with increased coffee intake. 

PMID- 24583405
TI  - Impaired hippocampal neurogenesis and its enhancement with ghrelin in 5XFAD mice.
AB  - Alzheimer's disease (AD) is an age-related neurological disorder characterized by
      the deposition of amyloid-beta (Abeta), cognitive deficits, and neuronal loss.
      The decline in neurogenic capacity could participate in neuronal vulnerability
      and contribute to memory impairment in AD. In our longitudinal study with AD
      model mice (5XFAD mice), we found that the number of doublecortin (neurogenesis
      marker)-positive cells in 5XFAD mice was significantly decreased compared to wild
      type littermate mice. Using Abeta immunostaining with 4G8 antibody, we observed
      that impairment in neurogenesis might be associated with the deposits of amyloid
      plaques. To investigate the effect of the neurogenic hormone ghrelin on defective
      neurogenesis in the AD brain, 5XFAD mice were administered peripherally with
      ghrelin. We found that treatment with ghrelin increased the number of
      doublecortin, HH3, and calretinin-stained cells in the hippocampus of 5XFAD mice.
      In 5XFAD mice treated with ghrelin, the 4G8-positive area was not significantly
      different from the saline-treated 5XFAD mice. Together, these findings suggest
      that hippocampal neurogenesis is impaired in 5XFAD mice and that treatment with
      ghrelin successfully rescued the abnormality of neurogenesis in 5XFAD mice
      without affecting Abeta pathology. 

PMID- 24583406
TI  - Resting state executive control network adaptations in amnestic mild cognitive
      impairment.
AB  - Executive dysfunction is frequently associated with episodic memory decline in
      amnestic mild cognitive impairment (aMCI) patients. Resting state executive
      control network (RS-ECN) represents a novel approach to interrogate the integrity
      of brain areas underlying executive dysfunction. The present study aims to
      investigate RS-ECN in aMCI and examine a possible link between changes in brain
      functional connectivity and declines in executive function. aMCI individuals (n =
      13) and healthy subjects (n = 16) underwent cognitive assessment including
      executive function and high field functional magnetic resonance imaging.
      Individual RS-ECN maps were estimated using a seed-based cross-correlation
      method. Between groups RS-ECN functional connectivity comparison was assessed
      using voxel-wise statistic parametric mapping. aMCI individuals had reduced RS
      ECN connectivity in the anterior cingulate cortex (ACC) and dorsal lateral
      prefrontal cortex (DLPFC), bilaterally. In contrast, aMCI showed increased
      connectivity in ventral lateral and anterior prefrontal cortex, bilaterally.
      Connectivity strength was associated with executive function in the ACC (r =
      0.6213, p = 0.023) and right DLPFC (r = 0.6454, p = 0.017). Coexistence between
      connectivity declines and recruitment of brain regions outside the RS-ECN as
      reported here fits a brain reserve conceptual framework in which brain networks
      undergo remodeling in aMCI individuals. 

PMID- 24583407
TI  - A novel mechanism for endogenous formaldehyde elevation in SAMP8 mouse.
AB  - Alzheimer's disease (AD) is the most common form of dementia, affecting millions
      of people worldwide. Increasing evidence suggests that formaldehyde might be one
      of the various pathological mechanisms involved in the process of AD onset. Here,
      we use an AD mouse model, senescence accelerated mouse-prone 8 strain (SAMP8), to
      study the relationship between endogenous formaldehyde and impairment of
      cognition. The Morris water maze test was used to evaluate the spatial learning
      and memory ability of 3-month-old SAMP8 mice, and we correlated the results with
      endogenous formaldehyde concentrations in the brain. To investigate the
      underlying reasons for formaldehyde elevation in neurodegenerative diseases, the
      expression levels of enzymes involved in formaldehyde metabolism were analyzed,
      including (anabolic) semicarbazide sensitive amine oxidase (SSAO) and (catabolic)
      alcohol dehydrogenase III (ADH3). When compared with age-matched SAMR1 mice, we
      found that in 3-month-old SAMP8 mice the capacity for spatial learning and memory
      was lower, while brain formaldehyde levels were higher. By using real-time PCR,
      western blotting, enzyme assay, and immunohistochemistry techniques, we
      discovered that SSAO expression levels were increased, whereas ADH3 exhibited
      reduced expression levels of mRNA, protein, and enzyme activity. The imbalance of
      these metabolic enzymes may represent a causal explanation for the observed
      formaldehyde elevation in the SAMP8 brain. Such increase could be responsible for
      the observed tau hyperphosphorylation assumed to result in protein aggregation,
      ultimately leading to cognitive impairment. Taken together, our study gives new
      insights into the role of metabolic enzymes in age-related accumulation of
      formaldehyde, and thus the establishment of neurodegenerative diseases. 

PMID- 24583408
TI  - Effects of nonylphenol exposure on expression of cell receptors and secretory
      function in mouse Sertoli TM4 cells.
AB  - The aim of this study was to investigate the effects of nonylphenol (NP) exposure
      on the expression of cell receptors and secretory function in mouse Sertoli TM4
      cells. There were no significant changes in mRNA expression of estrogen receptor
      (ER)-alpha and toll like receptor (TLR)-4 in the cells exposed to NP for 24h.
      However, the mRNA expression levels of ER-beta, progesterone receptor (PR) and
      androgen receptor (AR) were down-regulated in NP groups. Furthermore, NP
      treatment evoked significant changes in protein expression levels of ER-beta and
      follicle-stimulating hormone receptor (FSHR). There were significant changes in
      the mRNA expression levels of vinculin, N-cadherin and occludin, but not
      vimentin. Levels of inhibin B, androgen binding protein (ABP) and transferrin
      (Trf) were found to change significantly in NP challenged cells. Additionally,
      the decrease of nitric oxide (NO) production and inducible nitric oxide synthase
      (iNOS) mRNA expression and increase of cytokine levels were simultaneously found
      in NP stimulated TM4 cells. In conclusion, these findings have shown that NP
      exposure affected expression of cell receptors and may damage specific secretory
      function of Sertoli TM4 cells, which may be associated with the male-specific
      reproductive toxicity of NP. 

PMID- 24583409
TI  - Therapeutic potential of morin against liver fibrosis in rats: modulation of
      oxidative stress, cytokine production and nuclear factor kappa B.
AB  - Therapeutic potential of morin, a member of flavonoid family, against carbon
      tetrachloride (CCl4)-induced liver fibrosis in rats was investigated and compared
      with that of silymarin. Results show that treatment with morin (30 mg/kg/day)
      revealed attenuation in liver index and serum biomarkers of liver function that
      were enhanced by chronic CCl4 intoxication. Further, morin inhibited the elevated
      levels of malondialdehyde and nitric oxide and restored hepatic reduced
      glutathione to its normal level. The increased production of hepatic
      hydroxyproline content by CCl4 was markedly decreased by administration of morin.
      In addition, treatment with morin significantly attenuated the inflammatory
      responses caused by CCl4 as evident by the decreased hepatic tumor necrosis
      factor-alpha (TNF-alpha) level, immunohistochemical expressions of inducible
      nitric oxide synthase and nuclear factor kappa B. Collectively, this study
      indicates that morin possesses antifibrotic effect in the CCl4 model of fibrosis
      via reducing oxidative stress, inflammatory responses and fibrogenic markers.

PMID- 24583410
TI  - Effect of cadmium on the extracellular Na+, K+, and Ca2+ in the gill and small
      intestine of goldfish Carassius auratus.
AB  - In this study, the toxic effect of cadmium on extracellular Na(+), K(+), and
      Ca(2+) in the gill and small intestine of goldfish Carassius auratus was
      determined with the technique of ion chromatograph. Two-way ANOVA indicated that
      the two factors (Cd(2+) treatment and time) and the interaction factor had
      significant effect on the level of Na(+), K(+), and Ca(2+) in the small intestine
      and gill. 1.0 mg/L Cd(2+) significantly increased Ca(2+) level in the small
      intestine, but Ca(2+) level in the gill was significantly decreased by 1.0 and
      5.0 mg/L Cd(2+) at 24, 48, and 72 h. Na(+) and K(+) level in the small intestine
      and gill was increased by 1.0 mg/L Cd(2+) at three time points, but increased by
      5.0 mg/L Cd(2+) at a certain different time. In addition, Na(+) level was
      significantly decreased by 5.0 mg/L Cd(2+) at 24 or 48 h in the small intestine
      and gill. The results indicated that Cd(2+) played an important role in
      regulating the level of Na(+), K(+), and Ca(2+) in the small intestine and gill
      of goldfish C. auratus. A method was constructed to investigate the extracellular
      Na(+), K(+) and Ca(2+) in the tissues of gold fish with ion chromatography.

PMID- 24583411
TI  - RAG1 deficiency with a shifting B cell phenotype and chromosomal instability.

PMID- 24583412
TI  - Impact of cytomegalovirus replication and cytomegalovirus serostatus on the
      outcome of patients with B cell lymphoma after allogeneic stem cell
      transplantation.
AB  - Cytomegalovirus (CMV) replication after allogeneic hematopoietic stem cell
      transplantation (HSCT) was historically associated with increased nonrelapse
      mortality (NRM). More recently, different groups have reported an association
      between CMV replication and reduced risk of acute myeloid leukemia (AML) relapse.
      Given the conflicting results, we evaluated the impact of CMV replication and
      other covariates on the outcome of a retrospective cohort of 265 adults with B
      cell lymphoma receiving allogeneic HSCT from HLA-identical siblings or
      alternative donors. In time-dependent multivariate analysis, CMV replication,
      evaluated by pp65 antigenemia, had no independent effect on the risk of relapse
      (hazard ratio [HR], 1.0; 95% confidence interval [CI], .6 to 1.6; P = .9),
      although it was associated with a reduced overall survival (HR, 2.0; 95% CI, 1.3
      to 3.2; P = .001) and an increased NRM (HR, 2.5; 95% CI, 1.1 to 5.3; P = .01).
      Consistently, donor and/or recipient CMV seropositivity were not associated with
      a different outcome relative to CMV double-negative serostatus. In multivariate
      models, a diagnosis of follicular lymphoma (P < .0001) and pretransplantation
      complete remission status (P < .0001) were the main independent predictors for
      improved relapse-free survival. In summary, contrary to what is observed in
      patients with AML, this report identifies no independent role for CMV replication
      or serostatus on the relapse of patients with B cell lymphomas undergoing
      allogeneic HSCT.

PMID- 24583413
TI  - Regulatory focus and food choice motives. Prevention orientation associated with
      mood, convenience, and familiarity.
AB  - The authors tested the robustness of the Food Choice Questionnaire (FCQ) with a
      U.S. sample and examined the relationship between individual differences in
      regulatory focus and everyday food choice motives. Although a popular measure in
      cross-culture research, the FCQ has seen limited use with U.S. samples, and its
      psychometric properties have not been tested in this population. American
      participants (n = 408) completed the Regulatory Focus Questionnaire and a measure
      of food choice motives. The data did not support the nine-factor FCQ structure.
      An ad hoc revised measure of food choice motives showed complete measurement
      invariance (loadings, intercepts, and residuals) across regulatory focus.
      Regarding everyday food choices, participants with a prevention focus placed
      greater importance on mood, convenience, and familiarity than participants with a
      promotion focus. There were no significant differences regarding the importance
      of health, environmental protection, impression management, natural content,
      price, and sensory appeal. Several food choice motives were positively
      correlated. Compared with the promotion-focused participants, the prevention
      focused participants more strongly associated the importance of sensory appeal
      with the importance of natural content and the importance of price. 

PMID- 24583414
TI  - A systematic review of the effects of experimental fasting on cognition.
AB  - Numerous investigations have been conducted on the impact of short-term fasting
      on cognition in healthy individuals. Some studies have suggested that fasting is
      associated with executive function deficits; however, findings have been
      inconsistent. The lack of consensus regarding the impact of short-term fasting in
      healthy controls has impeded investigation of the impact of starvation or
      malnutrition in clinical groups, such as anorexia nervosa (AN). One method of
      disentangling these effects is to examine acute episodes of starvation
      experimentally. The present review systematically investigated the impact of
      short-term fasting on cognition. Studies investigating attentional bias to food
      related stimuli were excluded so as to focus on general cognition. Ten articles
      were included in the review. The combined results are equivocal: several studies
      report no observable differences as a result of fasting and others show specific
      deficits on tasks designed to test psychomotor speed, executive function, and
      mental rotation. This inconsistent profile of fasting in healthy individuals
      demonstrates the complexity of the role of short-term fasting in cognition; the
      variety of tasks used, composition of the sample, and type and duration of
      fasting across studies may also have contributed to the inconsistent profile.
      Additional focused studies on neuropsychological profiles of healthy individuals
      are warranted in order to better develop an understanding of the role of hunger
      in cognition. 

PMID- 24583415
TI  - Food prices and food shopping decisions of black women.
AB  - Identifying food pricing strategies to encourage purchases of lower-calorie food
      products may be particularly important for black Americans. Black children and
      adults have higher than average obesity prevalence and disproportionate exposure
      to food marketing environments in which high calorie foods are readily available
      and heavily promoted. The main objective of this study was to characterize
      effects of price on food purchases of black female household shoppers in
      conjunction with other key decision attributes (calorie content/healthfulness,
      package size, and convenience). Factorial discrete choice experiments were
      conducted with 65 low- and middle-/higher-income black women. The within-subject
      study design assessed responses to hypothetical scenarios for purchasing frozen
      vegetables, bread, chips, soda, fruit drinks, chicken, and cheese. Linear models
      were used to estimate the effects of price, calorie level (or healthfulness for
      bread), package size, and convenience on the propensity to purchase items.
      Moderating effects of demographic and personal characteristics were assessed.
      Compared with a price that was 35% lower, the regular price was associated with a
      lesser propensity to purchase foods in all categories (beta = -0.33 to -0.82
      points on a 1 to 5 scale). Other attributes, primarily calorie
      content/healthfulness, were more influential than price for four of seven foods.
      The moderating variable most often associated with propensity to pay the regular
      versus lower price was the reported use of nutrition labels. Price reductions
      alone may increase purchases of certain lower-calorie or more healthful foods by
      black female shoppers. In other cases, effects may depend on combining price
      changes with nutrition education or improvements in other valued attributes. 

PMID- 24583416
TI  - Effect of shear stress on water and LDL transport through cultured endothelial
      cell monolayers.
AB  - Previous animal experiments have shown that the transport of LDL into arterial
      walls is shear stress dependent. However, little work has probed shear effects on
      LDL transport in vitro where conditions are well defined and mechanisms are more
      easily explored. Therefore, we measured shear induced water and LDL fluxes across
      cultured bovine aortic endothelial (BAEC) monolayers in vitro and developed a
      three-pore model to describe the transport dynamics. Cell apoptosis was
      quantified by TdT-mediated dUTP nick end labeling (TUNEL) assay. We also examined
      the role of nitric oxide (NO) in shear induced water and LDL fluxes by incubating
      BAEC monolayers with an NO synthase inhibitor, NG-monomethyl-L-arginine (L-NMMA).
      Our results show that direct exposure of endothelial monolayers to 12 dyn/cm2
      shear stress for 3 h elicited a 2.37-fold increase in water flux (Jv), a 3.00
      fold increase in LDL permeability (Pe), a 1.32-fold increase in LDL uptake, and a
      1.68-fold increase in apoptotic rate. L-NMMA treatment of BAEC monolayers blocked
      shear induced Jv response, but had no significant effect on shear responses of Pe
      and cell apoptosis. A long time shear exposure (12 h) of endothelial monolayers
      reduced Pe and apoptotic rate close to the baseline. These results suggest that
      an acute change in shear stress from a static baseline state induces increases in
      water flux that are mediated by an NO dependent mechanism. On the other hand, the
      permeability of endothelial monolayers to LDL is enhanced by a short term-shear
      application and reduced nearly to the baseline level by a longer time shear
      exposure, positively correlated to the leaky junctions forming around apoptotic
      cells.

PMID- 24583418
TI  - Association between P-selectin glycoprotein ligand-1 and pathogenesis in acute
      coronary syndrome assessed by optical coherence tomography.
AB  - OBJECTIVE: Although monocytes appear to be actively involved in the onset of
      acute coronary syndrome (ACS), they are heterogenous in human peripheral blood.
      How up-regulation of monocyte subsets leads to coronary plaque rupture followed
      by thrombus formation remains unclear. Recent studies have shown that P-selectin
      glycoprotein ligand-1 (PSGL-1) is involved in monocyte activation in patients
      with thrombus formation. We therefore investigated the relationship between the
      expression of PSGL-1 on monocyte subsets and thrombus formation using frequency
      domain optical coherence tomography (FD-OCT) in patients with ACS. METHODS: We
      enrolled a total of 100 individuals in this study: patients with acute myocardial
      infarction (AMI, n=25), unstable angina pectoris (UAP, n=20), or stable angina
      pectoris (n=35) who underwent coronary angiography, and control subjects (n=20).
      Three monocyte subsets (CD14++CD16-, CD14++CD16+, and CD14+CD16+) and the
      expression of PSGL-1 were measured by flow cytometry. In patients with AMI and
      UAP, FD-OCT was performed before percutaneous coronary intervention. RESULTS:
      Circulating peripheral CD14++CD16+ monocytes expressed PSGL-1 more frequently
      than CD14++CD16- and CD14+CD16+ monocytes in patients with ACS. The expression of
      PSGL-1 on circulating peripheral CD14++CD16+ monocytes was significantly elevated
      in patients with AMI compared with the other 3 groups. Moreover, the expression
      levels of PSGL-1 on CD14++CD16+ monocytes were significantly higher in patients
      with plaque rupture or intracoronary thrombus assessed by FD-OCT. CONCLUSION: Up
      regulation of PSGL-1 on CD14++CD16+ monocytes may be a crucial role in plaque
      rupture and thrombus formation.

PMID- 24583417
TI  - Arterial compliance across the spectrum of ankle-brachial index: the Multiethnic
      Study of Atherosclerosis.
AB  - OBJECTIVE: A low ankle-brachial index is associated with cardiovascular disease
      and reduced arterial compliance. A high ankle-brachial index is also associated
      with an increased risk of cardiovascular events. We tested the hypothesis that
      subjects with a high ankle-brachial index demonstrate a lower arterial
      compliance. In addition, we assessed whether pulse pressure amplification is
      increased among subjects with a high ankle-brachial index. METHODS: We studied
      6814 adults enrolled in the Multiethnic Study of Atherosclerosis who were, by
      definition, free of clinical cardiovascular disease at baseline. Differences in
      total arterial compliance (ratio of stroke volume to pulse pressure), aortic and
      carotid distensibility (measured with magnetic resonance imaging and duplex
      ultrasound, respectively) were compared across ankle-brachial index subclasses
      (<=0.90, 0.91-1.29; >=1.30) with analyses adjusted for cardiovascular risk
      factors and subclinical atherosclerosis. RESULTS: Peripheral arterial disease was
      detected in 230 (3.4%) and high ABI in 648 (9.6%) of subjects. Those with high
      ankle-brachial index demonstrated greater aortic/radial pulse pressure
      amplification than those with a normal ankle-brachial index. In adjusted models
      aortic and carotid distensibility as well as total arterial compliance, were
      lowest among those with ankle-brachial index<=0.9 (p<0.01 vs. all), but were not
      reduced in subjects with an ankle-brachial index>=1.3. CONCLUSION: Lower aortic,
      carotid and total arterial compliance is not present in subjects free of overt
      cardiovascular disease and with a high ankle-brachial index. However, increased
      pulse pressure amplification contributes to a greater ankle-brachial index in the
      general population and may allow better characterization of individuals with this
      phenotype.

PMID- 24583419
TI  - Endothelial dysfuntion in children with idiopathic nephrotic syndrome.
AB  - BACKGROUND: Impaired endothelial function is the initial step in atherogenesis,
      which is largely responsible for ischaemic heart disease and thrombotic strokes
      decades later. METHODS: Fourty two children with first episode nephrotic syndrome
      (FENS) aged 1-16 years and 40 controls were enrolled. Soluble thrombomodulin
      (sTM), tissue plasminogen activator (t-PA), plasminogen activator inhibitor -1
      (PAI-1) and von-willebrand factor (vWF) levels were measured in plasma in FENS,
      at 12 weeks of drug induced remission and in steroid resistant nephrotic syndrome
      (SRNS) patients at diagnosis. RESULTS: PAI-1, sTM, vWF and t-PA were
      significantly raised at the onset of nephrotic syndrome (p<0.0001). All the
      markers had a fall after 12 weeks of steroid treatment, but were still raised.
      Children with SRNS had higher levels of sTM, tPA, vWF as compared to infrequent
      relapsers, at onset and at 4 weeks of steroid treatment. CONCLUSION: Children
      with idiopathic nephrotic syndrome have endothelial dysfunction which is largely
      dependent upon disease activity.

PMID- 24583420
TI  - Graves' ophthalmopathy: epidemiology and natural history.
AB  - Graves' ophthalmopathy (GO) is an autoimmune disorder of the orbit that is
      clinically relevant in 25-50% of patients with Graves' disease and 2% of patients
      with chronic thyroiditis. The age-adjusted annual incidence of clinically
      relevant GO is 16 per 100,000 population in women and 2.9 in men. At the onset of
      ophthalmopathy, 80-90% of patients have hyperthyroidism, with the rest having
      euthyroidism or hypothyroidism. The natural history of GO consists of two phases:
      an active inflammatory phase and a static phase. Anti-inflammatory therapy is
      indicated for the first phase of GO. Approximately 5% of patients experience late
      reactivation of GO. Asians appear to have less severe manifestations, with milder
      orbital edema, proptosis and muscle restriction. Genetic, anatomic and
      environmental factors influence the development of GO. Aging, thyroid
      dysfunction, thyroid stimulating hormone (TSH) receptor antibodies, smoking and
      radioiodine treatment for hyperthyroidism also influence the development and
      course of GO. 

PMID- 24583421
TI  - Biomarkers for multiple sclerosis.
AB  - Magnetic resonance imaging has been shown to be a powerful tool for diagnosing
      multiple sclerosis (MS) and evaluating surrogate markers of the disease activity.
      However, biomarkers may provide more accurate information regarding ongoing
      immune responses leading to demyelination and treatment effects in MS patients.
      Although serum biomarkers are easily accessible, they do not provide clear-cut
      results, whereas cerebrospinal fluid (CSF) biomarkers provide unequivocal
      information, although samples cannot be repeatedly obtained. For diagnosis, the
      presence of oligoclonal IgG bands remains important. In addition, measuring the
      levels of adhesion molecules, matrix metalloproteinase-9 and complement regulator
      factor H in the serum and evaluating the proportion of Th1/Th2 cells in the blood
      may be clinically feasible for monitoring the disease activity. In CSF samples,
      increased IL-8, IL-12, IL-17, CCL3, CCL5 and CXCL10 levels indicate active
      disease, and the flow cytometry findings of CSF cells can be used to detect
      increases in Th1 and CD4(+)CD25(+) cells during relapse. Biomarkers closely
      linked to the disease activity may be informative of the pathogenesis of MS,
      while those associated with tissue damage or repair may be targets of new
      treatment strategies. Establishing the latter will be a primary point of research
      in the near future. 

PMID- 24583422
TI  - Low-dose aspirin and comorbidities are significantly related to bleeding peptic
      ulcers in elderly patients compared with nonelderly patients in Japan.
AB  - OBJECTIVE: The present study was conducted using data accumulated from our
      earlier study of bleeding peptic ulcers, focusing on elderly patients. METHODS: A
      total of 461 patients with bleeding peptic ulcers underwent emergency endoscopy
      at Saga Medical School Hospital between 1999 and 2011. Risk factors for bleeding
      peptic ulcers were compared between two groups: an elderly group (>=65 years old)
      and a nonelderly group (<65 years old). The relationship between drug use and age
      was examined using multiple logistic regression models. In the elderly group, the
      factors were compared between Period I (1999-2005) and Period II (2006-2011).
      RESULTS: The proportion of men and the incidence of Helicobacter pylori infection
      were lower in the elderly group than in the nonelderly group. The use of low-dose
      aspirin, antithrombotic drugs and corticosteroids, but not nonsteroidal anti
      inflammatory drugs, was higher in the elderly group. A multiple logistic
      regression analysis of prescribed medications indicated that low-dose aspirin was
      more frequently used in the elderly group. The rate of comorbidities was higher
      and the hemoglobin levels were lower in the elderly group. The rates of
      rebleeding within one week and death within one month did not differ in the
      elderly group. Compared with that observed in Period I, the incidence of
      Helicobacter pylori infection was decreased and the rate of comorbidities was
      increased in Period II. CONCLUSION: This study indicates that factors related to
      bleeding peptic ulcers in elderly patients have shifted from Helicobacter pylori
      infection to comorbidities associated with low-dose aspirin, suggesting a close
      relationship between low-dose aspirin therapy and comorbidities in elderly
      patients with peptic ulcers.

PMID- 24583423
TI  - Immunochemical fecal occult blood tests predict dual antiplatelet therapy
      discontinuation after coronary stenting.
AB  - OBJECTIVE: The discontinuation of dual antiplatelet therapy (DAPT) increases the
      risk of stent thrombosis after coronary stenting. Some patients must discontinue
      DAPT due to gastrointestinal (GI) tract disease; however, the type of examination
      that is most useful for detecting GI tract diseases has not been fully evaluated.
      The purpose of this study was to clarify whether the immunochemical fecal occult
      blood test (iFOBT) can be used to predict GI tract disease-related DAPT
      discontinuation following stent implantation in patients with coronary artery
      disease. METHODS: A total of 181 consecutive DAPT-naive patients who underwent
      coronary stenting were divided into two groups according to the results of
      iFOBTs: a positive iFOBT group (n=32) and a negative iFOBT group (n=149). During
      the 12-month follow-up period, the DAPT discontinuation rate was lower in the
      negative iFOBT group than in the positive iFOBT group (3.4 vs. 18.8%, p=0.005).
      Kaplan-Meier event-free curves showed that the DAPT discontinuation rate in the
      negative iFOBT group was lower than that observed in the positive iFOBT group
      (log-rank test: p=0.001). Logistic and Cox regression analyses showed that a
      positive iFOBT result was the strongest predictor of the risk of DAPT
      discontinuation after coronary stenting. CONCLUSION: A positive iFOBT result is
      associated with DAPT discontinuation following coronary stenting.

PMID- 24583424
TI  - Relative contribution of insulin secretion and sensitivity at different stages of
      glucose tolerance: non-obese versus obese Japanese subjects.
AB  - OBJECTIVE: We examined the relative contribution of insulin secretion and insulin
      sensitivity at different stages of glucose tolerance in non-obese and obese
      Japanese subjects. METHODS: A total of 641 subjects who underwent 75-g glucose
      tolerance testing were divided into two groups: 436 non-obese subjects (body mass
      index: BMI <25) and 205 obese subjects (BMI >=25). The subjects were further
      divided into four groups: those with normal glucose tolerance (NGT), impaired
      fasting glucose (IFG), impaired glucose tolerance (IGT) and diabetes. We compared
      insulin secretion and sensitivity indices, such as the insulinogenic index (IGI),
      homeostatic model insulin resistance (HOMA-IR), homeostatic model assessment of
      beta-cell (HOMA-beta) and insulin sensitivity index (ISI). RESULTS: In a
      univariate analysis, the obese subjects had higher levels of HOMA-IR, HOMA-beta
      and IGI associated with lower ISI values in comparison with that observed in the
      non-obese subjects at different stages of glucose tolerance. A multiple logistic
      regression analysis showed that the HOMA-IR was a significant independent factor
      between the non-obese and obese subjects; the odds ratio (OR) (95% confidential
      interval: CI) was 3.78 (2.04-7.01; p<0.01) in the NGT group, 4.91 (2.06-11.72;
      p<0.01) in the IGT group and 2.02 (1.22-3.34; p<0.01) in the diabetes group.
      Although a similar trend was also observed in the IFG group (OR=15.83), the
      difference did not reach a level of statistical significance (p=0.066).
      CONCLUSION: These data suggest that obese subjects are characterized by increased
      insulin resistance rather than reduced insulin secretion at all stages of glucose
      tolerance. Therefore, non-obese subjects and obese subjects are distinct entities
      at all stages of glucose tolerance.

PMID- 24583425
TI  - Association of coronary artery calcification with MDA-LDL-C/LDL-C and urinary 8
      isoprostane in Japanese patients with type 2 diabetes.
AB  - OBJECTIVE: Oxidative stress has been implicated in the development of coronary
      artery calcification (CAC). However, there are few reports on this issue in
      Japanese patients with diabetes. In this study, we examined the association of
      the CAC score (CACS) with oxidative stress markers. METHODS: The study subjects
      were 163 Japanese patients with type 2 diabetes (75 men and 88 women). The CACS
      (Agatston unit: AU) was measured by multi-detector computed tomography (MDCT),
      and the oxidative stress markers, such as the urinary 8-isoprostane and 8
      hydroxydeoxyguanosine (8-OHdG) and serum malondialdehyde (MDA)-LDL cholesterol
      were measured. The relationships between CACS and oxidative stress markers were
      statistically analyzed. RESULTS: Compared with the CACS 0-400 AU group (n=132),
      the age, duration of diabetes, urinary 8-isoprostane levels, serum MDA-LDL-C/LDL
      C and maximum intima media thickness (IMT) were higher, and body mass index and
      HbA1c level were lower, in the CACS >400 AU group (n=31). The multiple logistic
      regression analysis showed that a CAC >400 AU was independently associated with
      the urinary 8-isoprostane (>median) (OR=2.54, 95% CI=1.03-6.32, p=0.044), MDA-LDL
      C/LDL-C (>median) (OR=2.62, 95% CI=1.07-6.40, p=0.035) and HbA1c (>median)
      (OR=0.32, CI=0.12-0.87, p<0.025). Focusing on oxidative stress, a higher MDA-LDL
      C/LDL-C (p=0.026) and a higher urinary 8-isoprostane level (p=0.074) were
      associated with the CACS. CONCLUSION: The CACS was found to be independently
      associated with the MDA-LDL-C/LDL-C and urinary 8-isoprostane levels in Japanese
      patients with type 2 diabetes.

PMID- 24583426
TI  - Nutritional indicators are correlated with the radiological severity score in
      patients with Mycobacterium avium complex pulmonary disease: a cross-sectional
      study.
AB  - OBJECTIVE: Body weight loss in patients with Mycobacterium avium complex (MAC)
      pulmonary disease can be fatal. The administration of nutritional supplements
      should be an important component in the treatment of this disease. Objective data
      regarding the association between the nutritional status and disease severity
      have not been reported. This cross-sectional study aimed to compare the
      nutritional status and radiological severity scores in MAC pulmonary disease
      patients. METHODS: We retrospectively reviewed the records of 40 patients who
      were admitted to our institution for the treatment of MAC pulmonary disease
      between July 2008 and July 2010. Nutritional indices, including the ideal body
      weight ratio, triceps skinfold, mid-upper arm muscle circumference, and
      percentage of predicted resting energy expenditure, were compared with the
      radiological severity scores. Quantitative values of the extent of nodules,
      infiltration shadows, cavities, and bronchiectasis on the computed tomography
      scans were used to evaluate the radiological severity scores. RESULTS: The
      patients suffered from a significantly decreased percentage of ideal body weight,
      body fat and muscle mass. The average radiological score was 17.6+/-8.4 points.
      The percentage of ideal body weight (p<0.001), percentage of triceps skinfold
      (p<0.001) and percentage of mid-upper arm muscle circumference (p<0.002) were
      negatively correlated with the radiological scores, while the percentage of the
      predicted resting energy expenditure (p<0.001) was positively correlated with the
      scores. CONCLUSION: A poor nutritional status is common in patients with
      progressive MAC pulmonary disease, which supports the hypothesis that aggressive
      nutritional interventions are indicated in the treatment of this disease.

PMID- 24583427
TI  - Clinical manifestations at diagnosis in Japanese patients with systemic AL
      amyloidosis: a retrospective study of 202 cases with a special attention to
      uncommon symptoms.
AB  - OBJECTIVE: To retrospectively investigate the clinical manifestations at
      diagnosis in Japanese patients with systemic AL amyloidosis. METHODS: We reviewed
      the medical records of 230 Japanese patients who had visited our hospital and
      been diagnosed with AL amyloidosis, and abstracted those with the systemic type.
      The clinical data at diagnosis of systemic AL amyloidosis, including laboratory
      and imaging findings, were analyzed. RESULTS: Two hundred and two patients (mean,
      58.7+/-9.5 years) were enrolled in this study. Immunofixation or
      immunoelectrophoresis was performed in 173 patients, 144 of whom were positive
      for M-protein in the serum and/or urine (kappa:lambda=30:114). The primary
      clinical manifestations at diagnosis were proteinuria and/or renal dysfunction
      (54.0%), congestive heart failure (24.8%), peripheral neuropathy (10.4%),
      hepatomegaly (7.9%) and arrhythmia (5.0%). The remaining patients developed
      unusual manifestations, such as solitary tumor, lymphadenopathy, gastrointestinal
      bleeding, intestinal pseudoobstruction, hemorrhagic tendencies and
      polyarthralgia. Dilatation of the intestine with marked thickening of the
      gastrointestinal wall on computed tomography and multiple nodular lesions with
      associated mucosal friability on endoscopy are characteristic findings of
      systemic AL amyloidosis. CONCLUSION: The clinical pictures of Japanese patients
      with systemic AL amyloidosis are similar to those previously reported from the US
      and European nations; however, some patients with this disease develop uncommon
      symptoms. Conducting laboratory and histological examinations for systemic AL
      amyloidosis is necessary when making a differential diagnosis of these symptoms.

PMID- 24583428
TI  - Elevated fibrin-related markers in patients with malignant diseases frequently
      associated with disseminated intravascular coagulation and venous
      thromboembolism.
AB  - OBJECTIVE: Many patients with malignant diseases are frequently complicated with
      some type of thrombosis, such as venous thromboembolism (VTE) or disseminated
      intravascular coagulation (DIC). METHODS: This retrospective study was designed
      to examine the frequency of thrombosis in 478 patients with malignant diseases in
      comparison to that observed in 121 patients without malignant diseases and to
      evaluate the efficacy of fibrin-related markers (FRMs), such as soluble fibrin,
      fibrinogen and fibrin degradation products and D-dimer, in diagnosing thrombosis.
      RESULTS: The frequency of thrombosis, including 62 cases of VTE, 63 cases of DIC
      and nine cases of cerebrovascular thrombosis, was significantly higher in the
      patients with malignant diseases (28.0%) than in the patients without malignant
      diseases (12.5%). DIC was frequently detected in the patients with hepatic cell
      cancer and hematopoietic malignancy, while VTE was frequently observed in the
      patients with colon cancer, breast cancer and urinary tract cancer. The FRMs
      levels were significantly higher in the patients with thrombosis than in the
      patients without thrombosis. A receiver operating characteristic analysis showed
      these markers to be useful for diagnosing thrombosis. CONCLUSION: Patients with
      malignant diseases have a high risk of thrombosis, and elevated FRMs levels are
      useful for diagnosing thrombosis in patients with malignant diseases.

PMID- 24583429
TI  - Parkinson's disease and the cardio-ankle vascular stiffness index.
AB  - OBJECTIVE: To investigate the relationship between Parkinson's disease (PD) and
      the cardio-ankle vascular stiffness index (CAVI), a novel non-invasive
      measurement of vascular stiffness. METHODS: A total of 63 PD subjects who
      underwent CAVI measurement were enrolled, including 30 men and 33 women 69.1+/
      7.5 years of age (range: 46-79 years). Sixty-three non-PD subjects (30 men, 33
      women, mean age: 68.7+/-7.6 years [range: 43-79 years]) served as controls.
      Comparisons between the control and PD subjects were made using Fisher's
      protected least significant difference, the Bonferroni-Dunn test, Scheffe's test
      and the unpaired t-test. RESULTS: 1) The average CAVI values were as follows:
      control, 9.3+/-0.9; PD, 9.0+/-1.0 (p=0.049). The differences in the CAVI values
      between the groups and the index values (normative data provided internally in
      the VaSera system) were as follows: control, 0.4+/-0.8; PD, 0.03+/-0.9 (p=0.011).
      The CAVI values of the PD patients were significantly smaller than those of the
      control subjects. 2) Among the control subjects, the CAVI values in the subjects
      with atherosclerotic risk factors (hypertension, dyslipidemia and/or diabetes)
      were significantly higher than those observed in the subjects without risk
      factors. In contrast, among the PD patients, the CAVI values in the subjects with
      atherosclerotic risk factors were equivalent to those observed in the subjects
      without risk factors. 3) Among the PD patients, the CAVI values did not change
      with the motor stage. CONCLUSION: The results of the present study show that,
      compared with control subjects, PD patients exhibit normal CAVI values despite
      having mild but significant atherosclerotic risk factors, e.g., hypertension and
      diabetes. These findings suggest that PD patients are less vulnerable to systemic
      atherosclerosis than their risk factors may suggest.

PMID- 24583430
TI  - Treatment with methotrexate and low-dose corticosteroids in sarcoidosis patients
      with cardiac lesions.
AB  - OBJECTIVE: Our objective was to evaluate the effectiveness of combination therapy
      consisting of low-dose corticosteroids with weekly methotrexate in patients with
      cardiac sarcoidosis in whom long-term therapy is required. Combination therapy
      was selected because long-term standard corticosteroid therapy tends to result in
      various adverse effects and the steroid-sparing effects of methotrexate have been
      reported. METHODS: This study was a small open-label study comparing long-term
      functional changes between patients who received combination therapy (5-15 mg/day
      of prednisolone and 6 mg/week of methotrexate) and patients who received
      corticosteroids alone. The comparative analysis was based on the following
      therapeutic indexes: ejection fraction (EF), left ventricular end-diastolic
      diameter (LVDd) on echocardiography, serum N-terminal fragment pro-brain
      natriuretic peptide (NT-proBNP) and cardiothoracic ratio (CTR) on plain chest
      radiographs. PATIENTS: Seventeen patients with cardiac sarcoidosis were examined
      in the sarcoidosis clinic. Cardiac sarcoidosis was diagnosed based on the
      Japanese diagnostic guidelines published in 2006. RESULTS: The EF was
      significantly stabilized in the combination therapy group but not in the
      corticosteroids alone group at three years after the first treatment. The CTR and
      NT-proBNP levels were significantly stabilized in the combination therapy group
      compared with those observed in the corticosteroids alone group at both three and
      five years after the first treatment. The LVDd values tended to be stable in the
      combination therapy group compared with those observed in the corticosteroids
      alone group. The combination therapy was associated with few adverse effects.
      CONCLUSION: Weekly methotrexate therapy with daily small doses of corticosteroids
      stabilized the EF, CTR and NT-proBNP levels in the serum without eliciting
      adverse effects longitudinally.

PMID- 24583431
TI  - Association between the hemoglobin levels and hypertension in relation to the BMI
      status in a rural Japanese population: the Nagasaki Islands Study.
AB  - OBJECTIVE: The hemoglobin levels and blood pressure has been reported in a few
      studies, and a positive association between the hemoglobin levels and the body
      mass index (BMI) status has also been documented. A higher BMI may therefore
      affect the association between the hemoglobin levels and hypertension. However,
      no published studies have examined this association in relation to the BMI
      status. The primary purpose of this study was to assess the association between
      the hemoglobin levels and hypertension in relation to the BMI status. METHODS: A
      cross-sectional study of 3,203 non-anemic subjects (1,191 men and 2,012 women, 30
      79 years old) who were undergoing general health checkups was conducted. RESULTS:
      A positive association between the hemoglobin levels and hypertension was
      established for both men and women. For a one SD (standard deviation) increment
      in hemoglobin, the multivariable odds ratio (ORs) and 95% confidence interval
      (CIs) for hypertension were 1.21 (95%CI: 1.05-1.40) for men and 1.25 (95%CI: 1.13
      1.39) for women. We also found that a significant association was confined to the
      participants with a BMI of <25 kg/m(2). Among the participants with a BMI of <25
      kg/m(2), the multivariable ORs and 95% CIs for hypertension of a one SD increment
      in hemoglobin were 1.34 (95%CI: 1.12-1.60) for men and 1.31 (95%CI: 1.16-1.47)
      for women. Meanwhile, among those with a BMI of >=25 kg/m(2), the corresponding
      values were 1.01 (95%CI: 0.79-1.30) and 1.09 (95%CI: 0.87-1.37). CONCLUSION: An
      independent positive association between the hemoglobin levels and the risk of
      hypertension was observed for both non-anemic Japanese men and women, confined to
      participants with a BMI of <25 kg/m(2).

PMID- 24583432
TI  - Left atrial myxoma detected after an initial diagnosis of polymyalgia rheumatica.
AB  - We herein report the case of a 69-year-old woman with left atrial myxoma detected
      following treatment with glucocorticoids for an initial diagnosis of polymyalgia
      rheumatica (PMR). The glucocorticoids markedly improved the patient's symptoms,
      and the tumor was excised after rapidly tapering the glucocorticoid dose. The PMR
      like symptoms did not recur and the inflammatory marker levels returned to normal
      after surgery. The patient's clinical course indicated that the initial PMR-like
      symptoms were entirely caused by the left atrial myxoma. This case demonstrates
      that glucocorticoid treatment for suspected PMR can mask the symptoms of myxoma,
      leading to a delay in diagnosis. 

PMID- 24583433
TI  - Gemcitabine-induced hemolytic uremic syndrome mimicking scleroderma renal crisis
      presenting with Raynaud's phenomenon, positive antinuclear antibodies and
      hypertensive emergency.
AB  - A 58-year-old woman who received gemcitabine for advanced gallbladder cancer
      developed an impaired renal function, thrombocytopenia, Raynaud's phenomenon,
      digital ischemic changes, a high antinuclear antibody titer and hypertensive
      emergency that mimicked a scleroderma renal crisis. A kidney biopsy specimen
      demonstrated onion-skin lesions in the arterioles and small arteries along with
      ischemic changes in the glomeruli, compatible with a diagnosis of hypertensive
      emergency (malignant hypertension). The intravenous administration of a calcium
      channel blocker, the oral administration of an angiotensin-converting enzyme
      inhibitor and angiotensin II receptor blocker and the transfusion of fresh frozen
      plasma were effective for treating the thrombocytopenia and progressive kidney
      dysfunction. Gemcitabine induces hemolytic uremic syndrome with accelerated
      hypertension and Raynaud's phenomenon, mimicking scleroderma renal crisis. 

PMID- 24583434
TI  - Hermansky-Pudlak syndrome with nonspecific interstitial pneumonia.
AB  - We herein report a case of Hermansky-Pudlak syndrome (HPS) with nonspecific
      interstitial pneumonia (NSIP). A 58-year-old Japanese woman presented with
      oculocutaneous albinism and dyspnea on exertion. A high resolution computed
      tomography scan showed areas of reticular and ground glass opacity in the lungs,
      and a surgical lung biopsy revealed fibrotic NSIP. Foamy type 2 pneumocytes and
      the absence of dense granules in platelets were also observed, consistent with a
      diagnosis of HPS. Ultimately, a genetic analysis revealed a mutation in the HPS1
      gene. The interstitial pneumonia progressed despite treatment with prednisolone,
      cyclosporine A and pirfenidone. In this report, we discuss the pathological lung
      features and treatment of HPS associated with interstitial pneumonia. 

PMID- 24583435
TI  - Two cases of pulmonary sarcoidosis presenting with subpleural reticular shadows
      in the lower lobes.
AB  - We herein report two unusual cases of sarcoidosis presenting with similar
      subpleural reticular shadows predominantly in the lower lobes with quite
      different pathological findings. In one patient, the lower lobe specimen
      contained typical epithelioid cell granulomas with subpleural and paraseptal
      fibrosis. However, the other patient exhibited usual interstitial pneumonia (UIP)
      in the lower lobe and sarcoidosis lesions in the upper lobe. Therefore, the
      latter patient was diagnosed with sarcoidosis complicated with UIP. Our results
      indicate that performing a surgical lung biopsy is necessary in order to provide
      appropriate management when lower lobe subpleural reticular shadows are present,
      even in patients with suspected sarcoidosis. 

PMID- 24583436
TI  - An anomalous unilateral single pulmonary vein associated with a bone
      morphogenetic protein receptor II gene mutation.
AB  - Anomalous unilateral single pulmonary vein (AUSPV), a rare congenital anomaly, is
      associated with an aberrant course but normal drainage, and resembles
      arteriovenous malformation (AVM). We treated a 26-year-old man with AUSPV in the
      right lung and an anomalous segmental pulmonary vein in the left lung. CT
      revealed a tortuous vascular shadow with an enhancement pattern identical to that
      of the pulmonary vein, suggesting AUSPV. This was confirmed by pulmonary
      angiography. Although pulmonary AVMs were not detected on angiography,
      microvascular AVMs could not be excluded because delayed bubbles appeared on
      contrast echocardiography. A genetic examination revealed a missense mutation of
      BMPR2. 

PMID- 24583437
TI  - "Dry" pleural mesothelioma successfully diagnosed on endobronchial ultrasound
      (EBUS)-guided transbronchial needle aspiration (TBNA).
AB  - The acquisition of histologic material is obligatory in order to establish the
      diagnosis of malignant pleural mesothelioma (MPM). In particular, tissue
      acquisition in cases of "dry" MPM (focal pleural thickening without pleural
      effusion or mediastinal lymph node involvement) is usually performed via a
      thoracoscopic pleural biopsy. In contrast, the techniques for performing
      echoendoscopic (transbronchial or transesophageal) needle aspiration of pleural
      lesions have only rarely been reported due to the theoretical limitations of
      tissue acquisition in such cases. We herein report the first case of "dry" MPM
      successfully diagnosed via endobronchial ultrasound-guided transbronchial needle
      aspiration (EBUS-TBNA) in a 73-year-old man presenting with a pleural mass in the
      right costovertebral recess, adjacent to the carina. The patient underwent
      radical resection, and a definitive pathological examination confirmed the
      diagnosis of epithelioid MPM. 

PMID- 24583438
TI  - Neurolymphomatosis in a patient with extranodal NK/T-cell lymphoma, nasal-type: a
      case report and literature review.
AB  - A 47-year-old man presented with a fever and lower extremity paresthesia. A
      physical examination revealed sensory deficits in the left hand, distal arm and
      right sole. A bone marrow aspiration demonstrated infiltration of extranodal NK/T
      cell lymphoma, nasal type, and (18)F-fluoro-2-deoxyglucose positron emission
      tomography (FDG-PET) disclosed extensive involvement of the peripheral nerves.
      These findings were consistent with a diagnosis of neurolymphomatosis (NL). The
      lymphoma progressed soon after the patient underwent cord blood transplantation,
      and he died on day 33 after transplantation. NL is a rare manifestation of
      lymphoma characterized by infiltration of the peripheral nerves, leading to
      neuropathy. It is an increasingly recognized entity and can be the first
      indication of lymphoma. 

PMID- 24583439
TI  - Antithrombin-p.Ala416Pro: the second reported case in Japan.
AB  - A 42-year-old man was referred to our department due to recurrent deep venous
      thrombosis. He, his father and his aunt had low antithrombin (AT) heparin
      cofactor activity and progressive AT activity levels with normal AT antigen
      levels. A single nucleotide substitution of G to C was found at nucleotide
      position c.1246 in exon 7 of the patient's AT gene, resulting in a p.Ala416Pro
      mutation of AT. The same mutation was identified in his father and aunt, but not
      his sister, who had a normal AT level. These results show that the AT-p.Ala416Pro
      mutation was responsible for type IIa AT deficiency in this family. 

PMID- 24583440
TI  - Creutzfeldt-Jakob disease with a codon 210 mutation: first pathological
      observation in a Japanese patient.
AB  - We herein report a case of Creutzfeldt-Jakob disease (CJD) with a V210I mutation
      and discuss the pathological findings. The patient's clinical course was quite
      similar to that of patients with sporadic CJD. Diffusion-weighted magnetic
      resonance imaging (MRI) disclosed a high signal intensity in the basal ganglia
      and cerebral cortices. Pathologically, spongiform degeneration of neurons and
      their processes with reactive astrocytosis was observed. Prion protein
      immunostaining revealed diffuse positive and plaque-type patterns. Only one
      Japanese case of CJD with this type of mutation has been reported to date, but
      without any pathological examination results. Therefore, this report is
      considered to be highly significant for understanding CJD. 

PMID- 24583441
TI  - Putaminal changes before the onset of clinical symptoms in diabetic hemichorea
      hemiballism.
AB  - An 81-year-old woman with poorly controlled diabetes mellitus was hospitalized
      due to hemichorea-hemiballism. A radiological examination revealed typical
      putaminal changes of diabetic hemichorea-hemiballism (DHC-HB). Interestingly,
      brain computed tomography, performed before symptom onset, disclosed a hyperdense
      lesion in the left basal ganglia, indicating persistent basal ganglia impairment,
      even before the onset of symptoms, under sustained hyperglycemia. Additionally,
      an increase in the cerebrospinal fluid level of homovanillic acid was related to
      the symptom appearance of DHC-HB. Pronounced potential basal ganglia impairment
      under hyperglycemia and central dopaminergic hyperactivity was important for the
      development of DHC-HB in this patient. 

PMID- 24583443
TI  - Adenovirus pneumonia presenting with nodular shadows on chest X-ray in two
      unrelated allogeneic bone marrow transplant recipients.
AB  - Adenoviruses are increasingly recognized as important pathogens following
      allogeneic stem cell transplantation. We herein report two cases of disseminated
      adenovirus infection that presented with nodular shadows on chest X-ray after
      allogeneic bone marrow transplantation from unrelated donors. Both patients died
      of respiratory failure. Autopsies revealed adenovirus infection of multiple
      organs. Adenovirus infection should be suspected when nodular lung lesions of
      unknown origin appear in allogeneic stem cell transplant recipients. 

PMID- 24583442
TI  - Pulmonary arterial hypertension associated with IgG4-related disease.
AB  - A 22-year-old woman with generalized lymphadenopathy and symmetrical swelling of
      the lacrimal and submandibular glands was diagnosed with IgG4-related disease.
      Biopsy specimens of the lips, lymph nodes, gastrointestinal tract and bronchus
      showed IgG4-positive plasma cell infiltration. Echocardiography and right heart
      catheterization revealed a high mean pulmonary arterial pressure. The patient was
      treated with 50 mg of prednisolone daily and rapidly improved. This is the first
      reported case of pulmonary arterial hypertension associated with IgG4-related
      disease. 

PMID- 24583444
TI  - Gonococcal endocarditis in a 47-year-old Japanese man.
AB  - A 47-year-old sexually active Japanese man was admitted with a persistent fever
      and weight loss. A physical examination revealed a cardiac murmur. A
      transthoracic echocardiogram was nondiagnostic, although blood cultures grew
      Neisseria gonorrhoeae. Gonococcal endocarditis was diagnosed based on the
      modified Duke criteria. The administration of antimicrobial therapy resulted in
      an adequate initial resolution; however, two months after completing the therapy,
      the patient developed cardiac failure. Severe aortic regurgitation was
      identified, and the patient underwent emergent aortic valve replacement. Despite
      the rarity of gonococcal endocarditis, this disease should nevertheless be
      considered in patients presenting with a fever, cardiac murmur and a consistent
      sexual history. 

PMID- 24583445
TI  - Acute generalized exanthematous pustulosis caused by daptomycin in a critically
      ill burn victim.
AB  - Acute generalized exanthematous pustulosis (AGEP) is a self-limiting type of drug
      eruption that frequently occurs as a reaction to antibiotics, particularly
      penicillins or macrolides. Daptomycin (DAP) is a newly developed antibiotic that
      specifically targets methicillin-resistant Staphylococcus aureus infection. We
      herein present the case of a 77-year-old severe burn victim who was diagnosed
      with DAP-induced AGEP while receiving treatment in an intensive care unit.
      Although rare, physicians should be aware that the administration of DAP can
      cause AGEP, which may complicate the clinical course of patients with a high
      fever and inflammation. 

PMID- 24583446
TI  - Radiographic findings of eosinophilic esophagitis.

PMID- 24583447
TI  - Characteristic CT signs of midgut volvulus.

PMID- 24583449
TI  - Pseudogout of the sternoclavicular joints.

PMID- 24583448
TI  - Coil migration following transcatheter arterial embolization.

PMID- 24583450
TI  - An infected urachal remnant in a young man.

PMID- 24583451
TI  - Misdiagnosis of Klippel-Trenaunay syndrome.

PMID- 24583452
TI  - Reply to the letter: Misdiagnosis of Klippel-Trenaunay syndrome.

PMID- 24583453
TI  - Anti-aquaporin-4 antibody-seronegative NMO spectrum disorder with Balo's
      concentric lesions.

PMID- 24583454
TI  - A case of anti-aquaporin-4 antibody-seronegative NMO spectrum disorder with Balo
      concentric lesions.

PMID- 24583455
TI  - Bayesian inferences about the self (and others): a review.
AB  - Viewing the brain as an organ of approximate Bayesian inference can help us
      understand how it represents the self. We suggest that inferred representations
      of the self have a normative function: to predict and optimise the likely
      outcomes of social interactions. Technically, we cast this predict-and-optimise
      as maximising the chance of favourable outcomes through active inference. Here
      the utility of outcomes can be conceptualised as prior beliefs about final
      states. Actions based on interpersonal representations can therefore be
      understood as minimising surprise - under the prior belief that one will end up
      in states with high utility. Interpersonal representations thus serve to render
      interactions more predictable, while the affective valence of interpersonal
      inference renders self-perception evaluative. Distortions of self-representation
      contribute to major psychiatric disorders such as depression, personality
      disorder and paranoia. The approach we review may therefore operationalise the
      study of interpersonal representations in pathological states. 

PMID- 24583456
TI  - Bias or equality? Unconscious thought equally integrates temporally scattered
      information.
AB  - In previous experiments on unconscious thought, information was presented to
      participants in one continuous session; however, in daily life, information is
      delivered in a temporally partitioned way. We examined whether unconscious
      thought could equally integrate temporally scattered information when making
      overall evaluations. When presenting participants with information in two
      temporally partitioned sessions, participants' overall evaluation was based on
      neither the information in the first session (Experiment 1) nor that in the
      second session (Experiment 2); instead, information in both sessions were equally
      integrated to reach a final judgment. Conscious thought, however, overemphasized
      information in the second session. Experiments 3 and 4 further ruled out possible
      influencing factors including differences in the distributions of
      positive/negative attributes in the first and second sessions and on-line
      judgment. These findings suggested that unconscious thought can integrate
      information from a wider range of periods during an evaluation, while conscious
      thought cannot. 

PMID- 24583457
TI  - Subjective aspects of working memory performance: memoranda-related imagery.
AB  - Although it is well accepted that working memory (WM) is intimately related to
      consciousness, little research has illuminated the liaison between the two
      phenomena. To investigate this under-explored nexus, we used an imagery
      monitoring task to investigate the subjective aspects of WM performance.
      Specifically, in two experiments, we examined the effects on consciousness of (a)
      holding in mind information having a low versus high memory load, and (b) holding
      memoranda in mind during the presentation of distractors (e.g., visual stimuli
      associated with a response incompatible with that of the memoranda). Higher rates
      of rehearsal (conscious imagery) occurred in the high load and distractor
      conditions than in comparable control conditions. Examination of the temporal
      properties of the rehearsal-based imagery revealed that, across subjects, imagery
      events occurred evenly throughout the delay. We hope that future variants of this
      new imagery monitoring task will reveal additional insights about WM,
      consciousness, and action control. 

PMID- 24583458
TI  - Carbon monoxide-releasing molecule 3 inhibits myeloperoxidase (MPO) and protects
      against MPO-induced vascular endothelial cell activation/dysfunction.
AB  - Polymorphonuclear leukocyte (PMN)-derived myeloperoxidase (MPO) contributes to
      the pathophysiology of numerous systemic inflammatory disorders through: (1)
      direct peroxidation of targets and (2) production of strong oxidizing compounds,
      e.g., hypohalous acids, particularly hypochlorous acid, which furthers oxidant
      damage and contributes to the propagation of inflammation and tissue
      injury/dysfunction. Carbon monoxide-releasing molecules (CORMs) offer potent anti
      inflammatory effects; however, the mechanism(s) of action is not fully
      understood. This study assessed the potential of MPO activity inhibition by a
      water-soluble CORM, CORM-3. To this end, we used in vitro assays to study CORM-3
      dependent modulation of MPO activity with respect to: (1) the inhibition of MPO's
      catalytic activity generally and (2) the specific inhibition of MPO's
      peroxidation and halogenation (i.e., production of hypochlorous acid) reactions.
      Further, we employed primary human umbilical vein endothelial cells (HUVECs) to
      investigate MPO-dependent cellular activation and dysfunction by measuring
      intracellular oxidant stress (DHR-123 oxidation) and HUVEC permeability (flux of
      Texas red-dextran), respectively. The results indicate that CORM-3 significantly
      inhibits MPO activity as well as MPO's peroxidation and hypohalous acid cycles
      specifically (p<0.05 vs uninhibited MPO). In addition, CORM-3 significantly
      decreases PMN homogenate- or rhMPO-induced intracellular DHR-123 oxidation in
      HUVECs and rhMPO-induced HUVEC monolayer permeability (p<0.05 vs untreated). In
      all assays the inactivated CORM-3 was significantly less effective than CORM-3
      (p<0.05). Taken together our findings indicate that CORM-3 is a novel MPO
      inhibitor and mitigates inflammatory damage at least in part through a mechanism
      involving the inhibition of neutrophilic MPO activity. 

PMID- 24583459
TI  - Effects of vitamin E on peroxisome proliferator-activated receptor gamma and
      nuclear factor-erythroid 2-related factor 2 in hypercholesterolemia-induced
      atherosclerosis.
AB  - Atherosclerosis and associated cardiovascular complications such as stroke and
      myocardial infarction are major causes of morbidity and mortality. We have
      previously reported a significant increase in mRNA levels of the scavenger
      receptor CD36 in aortae of cholesterol-fed rabbits and shown that vitamin E
      treatment attenuated increased CD36 mRNA expression. In the present study, we
      further investigated the redox signaling pathways associated with protection
      against atherogenesis induced by high dietary cholesterol and correlated these
      with CD36 expression and the effects of vitamin E supplementation in a rabbit
      model. Male albino rabbits were assigned to either a control group fed with a low
      vitamin E diet alone or a test group fed with a low vitamin E diet containing 2%
      cholesterol in the absence or presence of daily intramuscular injections of
      vitamin E (50mg/kg). To elucidate the mechanisms by which vitamin E
      supplementation alters the effects of hypercholesterolemia in rabbit aortae, we
      measured peroxisome proliferator-activated receptor gamma (PPARgamma), ATP
      binding cassette transporter A1 (ABCA1), and matrix metalloproteinase-1 (MMP-1)
      mRNA levels by quantitative RT-PCR and the expression of MMP-1, nuclear factor
      erythroid 2-related factor 2 (Nrf2), and glutathione S-transferase alpha
      (GSTalpha) protein by immunoblotting. The increased MMP-1 and decreased GSTalpha
      expression observed suggests that a cholesterol-rich diet contributes to the
      development of atherosclerosis, whereas vitamin E supplementation affords
      protection by decreasing MMP-1 and increasing PPARgamma, GSTalpha, and ABCA1
      levels in aortae of rabbits fed a cholesterol-rich diet. Notably, protein
      expression of Nrf2, the antioxidant transcription factor, was increased in both
      the cholesterol-fed and the vitamin E-supplemented groups. Although Nrf2
      activation can promote CD36-mediated cholesterol uptake by macrophages, the
      increased induction of Nrf2-mediated antioxidant genes is likely to contribute to
      decreased lesion progression. Thus, our study demonstrates that Nrf2 can mediate
      both pro- and antiatherosclerotic effects. 

PMID- 24583460
TI  - Shikonin targets cytosolic thioredoxin reductase to induce ROS-mediated apoptosis
      in human promyelocytic leukemia HL-60 cells.
AB  - Shikonin, a major active component of the Chinese herbal plant Lithospermum
      erythrorhizon, has been applied for centuries in traditional Chinese medicine.
      Although shikonin demonstrates potent anticancer efficacy in numerous types of
      human cancer cells, the cellular targets of shikonin have not been fully defined.
      We report here that shikonin may interact with the cytosolic thioredoxin
      reductase (TrxR1), an important selenocysteine (Sec)-containing antioxidant
      enzyme with a C-terminal -Gly-Cys-Sec-Gly active site, to induce reactive oxygen
      species (ROS)-mediated apoptosis in human promyelocytic leukemia HL-60 cells.
      Shikonin primarily targets the Sec residue in TrxR1 to inhibit its physiological
      function, but further shifts the enzyme to an NADPH oxidase to generate
      superoxide anions, which leads to accumulation of ROS and collapse of the
      intracellular redox balance. Importantly, overexpression of functional TrxR1
      attenuates the cytotoxicity of shikonin, whereas knockdown of TrxR1 sensitizes
      cells to shikonin treatment. Targeting TrxR1 with shikonin thus discloses a
      previously unrecognized mechanism underlying the biological activity of shikonin
      and provides an in-depth insight into the action of shikonin in the treatment of
      cancer. 

PMID- 24583461
TI  - Bioartificial fabrication of regenerating blood vessel substitutes: requirements
      and current strategies.
AB  - This work reviews the tremendous development in the field of vascular graft
      tissue engineering driven by a clear and increasing clinical need for functional
      vascular replacements able to grow and remodel. The different strategies to
      tissue engineer blood vessels are presented, from the classical approach of a
      living implant generated in vitro by conditioning a cell-seeded scaffold to
      remarkable paradigm shifts either i) toward a completely biology-driven strategy
      (scaffold-free approaches) or ii) the opposite tendency of cell-free scaffolds
      aiming at eliciting the host reaction for in situ tissue engineering. In the
      scaffold-based approaches emphasis is given to the material choice.

PMID- 24583462
TI  - Feasibility of an EQAS for HbA1c in Italy using fresh blood samples.

PMID- 24583463
TI  - Inflammatory bowel diseases: where we are and where we should go.

PMID- 24583465
TI  - Evaluation of fructooligosaccharides separation using a fixed-bed column packed
      with activated charcoal.
AB  - Recent studies have shown that the chromatographic separation of mixtures of
      saccharides may be improved by making use of activated charcoal, a promising low
      cost material for the separation of sugars, including fructooligosaccharides. In
      this work, the development of a methodology to separate fructooligosaccharides
      from glucose, fructose and sucrose, using a fixed bed column packed with
      activated charcoal is proposed. The influence of temperature, eluant
      concentration and step gradients were evaluated to increase the separation
      efficiency and fructooligosaccharide purity. The final degree of
      fructooligosaccharide purification and separation efficiency were about 94% and
      3.03 respectively, using ethanol gradient concentration ranging from 3.5% to 15%
      (v/v) at 40 degrees C. The fixed bed column packed with the activated charcoal
      was shown to be a promising alternative for sugar separation, mainly those rich
      in fructooligosaccharides, leading to solutions of acceptable degrees of
      purification. 

PMID- 24583466
TI  - A large-area 15 nm graphene nanoribbon array patterned by a focused ion beam.
AB  - Using a focused ion beam, we patterned epitaxial graphene on SiC into an array of
      graphene nanoribbons as narrow as 15 nm by optimizing the Ga(+) ion beam current,
      acceleration voltage, dwell time, beam center-to-center distance and ion dose.
      The ion dose required to completely etch away graphene on SiC was determined and
      compared with the Monte Carlo simulation result. In addition, a photodetector
      using an array of 300 20 nm graphene nanoribbons was fabricated and its
      photoresponse was studied.

PMID- 24583468
TI  - Exposure to Outgroup Members Criticizing Their Own Group Facilitates Intergroup
      Openness.
AB  - A major barrier to conflict resolution is group members' tendency to hold on to
      the ingroup's narrative of the conflict and reject the outgroup's perspective. In
      the current research, we propose that voicing internal criticism to an outgroup
      crowd can undermine such orientations and foster intergroup openness. Across four
      experiments, Israeli Jews who were exposed to a Palestinian criticizing
      Palestinians were more open to the Palestinians' perspective of the conflict,
      than those not exposed to the criticism. This effect was obtained when the
      criticism was related (Study 1) and unrelated (Study 2) to the conflict, and was
      consistently mediated by increased hope about the future relations between the
      groups. Study 3 showed that the effect is more pronounced among those who believe
      that groups can change. Study 4 established that perceptions about the outgroup
      as open-minded underlie the effect of ingroup criticism on hope, and further
      demonstrated downstream effects of openness.

PMID- 24583467
TI  - Nuclear accumulation of cyclin D1 following long-term fractionated exposures to
      low-dose ionizing radiation in normal human diploid cells.
AB  - Cyclin D1 is a mitogenic sensor that responds to growth signals from the
      extracellular environment and regulates the G 1-to-S cell cycle transition. When
      cells are acutely irradiated with a single dose of 10 Gy, cyclin D1 is degraded,
      causing cell cycle arrest at the G 1/S checkpoint. In contrast, cyclin D1
      accumulates in human tumor cells that are exposed to long-term fractionated
      radiation (0.5 Gy/fraction of X-rays). In this study we investigated the effect
      of fractionated low-dose radiation exposure on cyclin D1 localization in 3
      strains of normal human fibroblasts. To specifically examine the nuclear
      accumulation of cyclin D1, cells were treated with a hypotonic buffer containing
      detergent to remove cytoplasmic cyclin D1. Proliferating cell nuclear antigen
      (PCNA) immunofluorescence was used to identify cells in S phase. With this
      approach, we observed S-phase nuclear retention of cyclin D1 following low-dose
      fractionated exposures, and found that cyclin D1 nuclear retention increased with
      exposure time. Cells that retained nuclear cyclin D1 were more likely to have
      micronuclei than non-retaining cells, indicating that the accumulation of nuclear
      cyclin D1 was associated with genomic instability. Moreover, inhibition of the v
      akt murine thymoma viral oncogene homolog (AKT) pathway facilitated cyclin D1
      degradation and eliminated cyclin D1 nuclear retention in cells exposed to
      fractionated radiation. Thus, cyclin D1 may represent a useful marker for
      monitoring long-term effects associated with exposure to low levels of radiation.

PMID- 24583469
TI  - Pushing in the Dark: Causes and Consequences of Limited Self-Awareness for
      Interpersonal Assertiveness.
AB  - Do people know when they are seen as pressing too hard, yielding too readily, or
      having the right touch? And does awareness matter? We examined these questions in
      four studies. Study 1 used dyadic negotiations to reveal a modest link between
      targets' self-views and counterparts' views of targets' assertiveness, showing
      that those seen as under- and over-assertive were likely to see themselves as
      appropriately assertive. Surprisingly, many people seen as appropriately
      assertive by counterparts mistakenly thought they were seen as having been over
      assertive, a novel effect we call the line crossing illusion. We speculated that
      counterparts' orchestrated displays of discomfort might be partly responsible
      behaviors we termed strategic umbrage. Study 2 revealed evidence for widespread
      strategic umbrage in real-world negotiations and Study 3 linked these behaviors
      to the line crossing illusion in a controlled negotiation. Study 4 showed that
      this illusion predicted outcomes in a multi-round negotiation.

PMID- 24583470
TI  - Synthesis, crystal growth and physical characterizations of organic nonlinear
      optical crystal: Ammonium hydrogen L-malate.
AB  - An organic nonlinear optical crystal ammonium hydrogen l-malate (AHM) has been
      synthesized. Single crystals of AHM have successfully been grown by the slow
      evaporation solution method. Optically clear single crystals having dimensions up
      to 23*9*4mm(3) have been grown. Single crystal X-ray diffraction study confirms
      that the AHM crystallizes in orthorhombic crystal system with space group
      P212121. The powder X-ray diffraction pattern of the grown crystal has been
      recorded. FT-IR spectrum was recorded to identify the various functional groups
      of AHM. The UV-vis-NIR transmission was analyzed for grown crystal. Thermal
      analysis was performed to find out thermal stability of the compound. Vickers
      microhardness measurements were carried and also work hardening coefficient has
      been found. The crystalline perfection of the grown crystal has been analyzed by
      HRXRD measurements. The second harmonic efficiency of AHM was found to be 1.2
      times that of KDP. 

PMID- 24583471
TI  - Influence of vacuum upon preparation and luminescence of Si4+ and Ti4+ codoped
      Gd2O2S:Eu phosphor.
AB  - As a novel red long afterglow phosphor, Si(4+) and Ti(4+) ion codoped Gd2O2S:Eu
      phosphor with spherical morphology, sub-micrometer size and narrow particle size
      distribution was synthesized by solid-state reaction in vacuum. The vacuum
      synthesis mechanism was determined by thermal analysis. The crystal structure,
      luminescence properties and mechanisms were investigated respectively by XRD, SEM
      and fluorescence spectrophotometer. The results show that well-crystallized
      Gd2O2S:Eu,Si,Ti phosphors are of hexagonal structure which is in agreement with
      the standard powder peak positions of Gd2O2S hexagonal phase. It displays pure
      red emission because of the strongest peaks at 627nm and 617nm which are
      attributed to energy transfer ((5)D0-(7)F2). There is a little blue shift of
      charge transfer excitation band in the excitation spectra between the bulk and
      sub-micrometer-sized samples, which may stem from size dependent shift and
      different lattice distortion in the position of the Eu(3+)-ligand electron
      transfer absorption/excitation band. To further study the influence of the
      impurities in Gd2O2S:Eu crystals on crystal growth, the simulated crystal face
      and its XRD patterns were illustrated. The preferred orientation of crystal
      growth changed from crystal face (101) to (100) thus to result in different
      luminescence mechanisms. 

PMID- 24583472
TI  - Broadband near-infrared emission property in Er3+/Ce3+ co-doped silica-germanate
      glass for fiber amplifier.
AB  - Er(3+) doped and Er(3+)/Ce(3+) co-doped silica-germanate glasses were synthesized
      by high-temperature melt-quenching technique. A detailed study of the 1.53MUm
      spectroscopic properties and thermal stability was presented in this work. The
      absorption spectra, 1.53MUm emission spectra and fluorescence lifetimes were
      measured and investigated, along with the quantitative calculations and analyses
      of Judd-Ofelt intensity parameters, stimulated absorption and emission cross
      sections and the product of FWHM*sigmaem(p). It was found that the prepared
      samples have outstanding thermal stability (Tg=585 degrees C), large FWHM (77nm
      and 108nm) and high stimulated emission cross-sections (9.55*10(-28)cm(3) and
      8.72*10(-28)cm(3)) of Er(3+). The 1.53MUm fluorescence intensity improved
      significantly with the introduction of Ce(3+). Furthermore, the wavelength
      dependent gain coefficient G(lambda) of (4)I13/2->(4)I15/2 transition of Er(3+)
      was determined by means of the absorption and emission cross-sections. The
      results indicate that the developed glass co-doped with Er(3+)/Ce(3+) is a
      promising gain medium applied for broadband amplifier pumped with a 980nm laser
      diode. 

PMID- 24583473
TI  - Studies the alterations of biochemical and mineral contents in bone tissue of mus
      musculus due to aluminum toxicity and the protective action of desferrioxamine
      and deferiprone by FTIR, ICP-OES, SEM and XRD techniques.
AB  - The present study has attempt to analyze the changes in the biochemical and
      mineral contents of aluminum intoxicated bone and determine the protective action
      of desferrioxamine (DFO) and deferiprone (DFP) by using Fourier transform
      infrared (FTIR) spectroscopy, X-ray diffraction (XRD), inductively coupled plasma
      optical emission spectroscopy (ICP-OES), and scanning electron microscopy (SEM)
      techniques for four groups of animals such as control (Group I), aluminum
      intoxicated (Group II), Al+DFP (Group III) and Al+DFO+DFP (Group IV) treated
      groups respectively. The FTIR spectra of the aluminum intoxicated bone showed
      significant alteration in the biochemical constituents. The bands ratio at
      I1400/I877 significantly decreased from control to aluminum, but enhanced it by
      Al+DFP to Al+DFO+DFP treated bone tissue for treatments of 16 weeks. This result
      suggests that DFO and DFP are the carbonate inhibitor, recovered from chronic
      growth of bone diseases and pathologies. The alteration of proteins profile
      indicated by Amide I and Amide II, where peak area values decreased from control
      to aluminum respectively, but enhanced by treated with DFP (p.o.) and DFO+DFP
      (i.p.) respectively. The XRD analysis showed a decrease in crystallinity due to
      aluminum toxicity. Further, the Ca, Mg, and P contents of the aluminum exposed
      bone were less than those of the control group, and enhanced by treatments with
      DFO and DFP. The concentrations of trace elements were found by ICP-OES.
      Therefore, present study suggests that due to aluminum toxicity severe loss of
      bone minerals, decrease in the biochemical constituents and changes in the
      surface morphology.

PMID- 24583474
TI  - Colorectal cancer progression: lessons from Drosophila?
AB  - Human colorectal cancers arise as benign adenomas, tumours that retain their
      epithelial character, and then progress to malignant adenocarcinomas and
      carcinomas in which the epithelium becomes disrupted. Carcinomas often exhibit
      transcriptional downregulation of E-cadherin and other epithelial genes in an
      epithelial-to-mesenchymal transition (EMT), a mechanism first discovered in
      Drosophila to be mediated by the transcription factors Twist and Snail. In
      contrast, adenocarcinomas retain expression of E-cadherin and disruption of the
      epithelium occurs through formation of progressively smaller epithelial cysts
      with apical Crumbs/CRB3, Stardust/PALS1, and Bazooka/PAR3 localised to the inner
      lumen. Results from Drosophila show that morphologically similar cysts form upon
      induction of clonal heterogeneity in Wnt, Smad, or Ras signalling levels, which
      causes extrusion of epithelial cells at clonal boundaries. Thus, intratumour
      heterogeneity might also promote formation of adenocarcinomas in humans. Finally,
      epithelial cysts can collectively migrate, as in the case of Drosophila border
      cells, a potential model system for the invasive migration of adenocarcinoma
      cells. 

PMID- 24583475
TI  - The impact of metabolic syndrome on inpatient outcomes after isolated ankle
      fractures.
AB  - BACKGROUND: Metabolic syndrome has been associated with increased morbidity
      following surgical procedures, yet its impact in acute orthopaedic trauma remains
      unclear. The purpose of this study was to evaluate the influence of metabolic
      syndrome on in-hospital (1) complications, (2) length of stay, and (3) nonroutine
      discharge in patients sustaining an isolated ankle fracture. METHODS: Using the
      National Health Discharge Survey (NHDS) database for the years 2001 through 2007,
      an estimated 669 841 patients with isolated ankle fractures treated operatively
      were identified and separated into groups with and without metabolic syndrome.
      Multivariable binary logistic regression analysis was performed for each of the
      outcome variables. RESULTS: Metabolic syndrome was an independent risk factor for
      increased nonroutine discharge (OR = 1.8) and the development of in-hospital
      complications (OR = 2.1). The presence of metabolic syndrome was not an
      independent risk factor for prolonged hospital stay. CONCLUSION: Patients with
      metabolic syndrome sustaining an isolated ankle fracture are at increased risk
      for in-hospital complications and a less rapid return of independent functional
      mobility, as evidenced by the higher need for posthospitalization care. LEVEL OF
      EVIDENCE: Level III, epidemiologic study.

PMID- 24583476
TI  - MicroRNA-155 is involved in the pathogenesis of ulcerative colitis by targeting
      FOXO3a.
AB  - BACKGROUND: MicroRNAs (miRNAs) are important posttranscriptional regulators of
      gene expression. The precise role of miRNAs in ulcerative colitis (UC) is not
      completely understood. The purpose of this study was to identify miRNAs that are
      induced in patients with active UC and to assess the effect of miR-155 on
      improving intestinal inflammation. METHODS: The miRNA profiles in patients with
      active UC (n = 20) and healthy subjects (n = 16) were examined using miRNA
      microarrays. miR-155 upregulation was confirmed by quantitative RT-PCR.
      Regulation of the target gene FOXO3a expression by miR-155 was assessed using
      luciferase reporter construct assays and miR-155 mimic or inhibitor
      transfections. The effects of FOXO3a or miR-155 on IkappaBalpha or IL-8 were
      detected by Western blot or enzyme-linked immunosorbent assay in HT29 cells,
      respectively. RESULTS: We identified 68 miRNAs that were differentially expressed
      (33 upregulated and 35 downregulated) in patients with active UC compared with
      healthy controls. One of the upregulated miRNAs in the UC tissue was miR-155
      (1.22-fold, P < 0.03), which plays a key role in the regulation of inflammatory
      pathways. In patients with active UC, miR-155 was significantly upregulated, and
      the expression of FOXO3a dramatically decreased. Luciferase reporter assays
      demonstrated that miR-155 directly targets FOXO3a and affects the protein
      expression of FOXO3a in HT29 cells. Moreover, silenced FOXO3a and the
      overexpression of miR-155 increased the levels of IL-8 in TNF-alpha-treated HT29
      cells by suppressing the inhibitory IkappaBalpha. CONCLUSIONS: miR-155 appears to
      play a role in the intestinal inflammation of patients with active UC by
      downregulating the expression of FOXO3a. This process may activate the nuclear
      factor kappa B signaling pathway.

PMID- 24583477
TI  - Colonic expression of the peptide transporter PEPT1 is downregulated during
      intestinal inflammation and is not required for NOD2-dependent immune activation.
AB  - BACKGROUND: PEPT1 was proposed to be expressed only in inflamed colonic tissues
      in which it could contribute to inflammatory bowel disease (IBD) development by
      transporting bacterial peptides, such as muramyl dipeptide (MDP), that activate
      intracellular pattern recognition receptors, such as the nucleotide-binding and
      oligomerization domain 2. To better define the pathological relevance of this
      transporter, we analyzed PEPT1 expression during intestinal inflammation and
      studied the susceptibility of Pept1-deficient (Pept1) mice to experimental
      colitis. METHODS: Wild-type and Pept1 mice were treated with dextran sulfate
      sodium and 2,4,6-trinitrobenzene sulfonic acid to induce colitis, and MDP-induced
      cytokine expression was studied in colonic tissue cultures. PEPT1 expression was
      characterized in mouse models of Crohn's disease-like ileitis (Tnf) or colitis
      (Il-10, Il-10XTlr2) and endoscopic tissue samples from descending colon of
      patients with IBD (n = 11) and controls (n = 17). Moreover, the prevalence of the
      PEPT1 single-nucleotide polymorphism rs2297322 was tested in German patients with
      IBD (n = 458) and controls (n = 452). RESULTS: PEPT1 expression was consistently
      reduced under condition of acute or chronic experimental inflammation. Wild-type
      and Pept1 mice revealed comparable susceptibility to dextran sulfate sodium
      induced and 2,4,6-trinitrobenzene sulfonic acid-induced colitis, and MDP-induced
      cytokine expression was PEPT1-independent. PEPT1 expression levels were also
      decreased in descending colon of patients with IBD during acute inflammation, but
      the rs2297322 single-nucleotide polymorphism was not associated with IBD
      susceptibility in the German cohort. CONCLUSIONS: PEPT1 expression is reduced
      during intestinal inflammation and PEPT1 is neither required for MDP-induced
      immune response nor is the PEPT1 rs2297322 single-nucleotide polymorphism
      associated with IBD susceptibility in our German cohort. These data strongly
      argue against a primary role of PEPT1 in the initiation or progression of IBD.

PMID- 24583478
TI  - Prevalence of and outcomes associated with corticosteroid prescription in
      inflammatory bowel disease.
AB  - BACKGROUND: Corticosteroids are widely used in the management of inflammatory
      bowel disease (IBD) and are associated with significant side effects. The real
      world effectiveness of newer drug therapies at reducing corticosteroid use is yet
      to be reported. The overall burden of corticosteroid use is poorly characterized.
      METHODS: We used a population-based IBD database to evaluate the overall
      prevalence of corticosteroid exposure, corticosteroid-free survival, and heavy
      corticosteroid use (>=3000 mg of prednisone or equivalent in a 365-day period).
      Regression models were used to assess predictors of heavy corticosteroid use and
      the relationship between corticosteroid dose in the first year after diagnosis
      and the need for continued corticosteroid use and surgery. RESULTS: The
      proportion of persons with IBD prescribed corticosteroids within 1, 5, and 10
      years of diagnosis was 35.2%, 52.0%, and 62.8%, respectively. Persons with
      ulcerative colitis, males, and diagnosis before age 25 were more likely to use
      corticosteroids and have higher cumulative exposure. Heavy corticosteroid use in
      the first year after IBD diagnosis was associated with a 3 times increased hazard
      of resective surgery. Cumulative corticosteroid exposure did not decrease among
      those diagnosed with IBD in more recent years, despite increasing use of
      immunomodulators. CONCLUSIONS: A plurality of IBD patients will be exposed to
      corticosteroids over the course of disease, mostly in the first year. Heavy
      corticosteroid use in the first year of IBD is a strong predictor of subsequent
      surgery. Cumulative exposure to corticosteroids use is not decreasing despite
      increasing uptake of immunomodulators.

PMID- 24583480
TI  - Instruments for assessing risk of bias and other methodological criteria: Krauth
      et al. Respond.

PMID- 24583481
TI  - Hero: David Satcher, MD, PhD.

PMID- 24583479
TI  - Metabolic alterations to the mucosal microbiota in inflammatory bowel disease.
AB  - BACKGROUND: Inflammation during inflammatory bowel disease may alter nutrient
      availability to adherent mucosal bacteria and impact their metabolic function.
      Microbial metabolites may regulate intestinal CD4 T-cell homeostasis. We
      investigated the relationship between inflammation and microbial function by
      inferred metagenomics of the mucosal microbiota from colonic pinch biopsies of
      patients with inflammatory bowel disease. METHODS: Paired pinch biopsy samples of
      known inflammation states were analyzed from ulcerative colitis (UC) (23),
      Crohn's disease (CD) (21), and control (24) subjects by 16S ribosomal sequencing,
      histopathologic assessment, and flow cytometry. PICRUSt was used to generate
      metagenomic data and derive relative Kyoto Encyclopedia of Genes and Genomes
      Pathway abundance information. Leukocytes were isolated from paired biopsy
      samples and analyzed by multicolor flow cytometry. Active inflammation was
      defined by neutrophil infiltration into the epithelium. RESULTS: Carriage of
      metabolic pathways in the mucosal microbiota was relatively stable among patients
      with inflammatory bowel disease, despite large variations in individual bacterial
      community structures. However, microbial function was significantly altered in
      inflamed tissue of UC patients, with a reduction in carbohydrate and nucleotide
      metabolism in favor of increased lipid and amino acid metabolism. These
      differences were not observed in samples from CD patients. In CD, microbial
      lipid, carbohydrate, and amino acid metabolism tightly correlated with the
      frequency of CD4Foxp3 Tregs, whereas in UC, these pathways correlated with the
      frequency of CD4IL-22 (TH22) cells. CONCLUSIONS: Metabolic pathways of the
      mucosal microbiota in CD do not vary as much as UC with inflammation state,
      indicating a more systemic perturbation of host-bacteria interactions in CD
      compared with more localized dysfunction in UC.

PMID- 24583483
TI  - Engaging underserved populations in Affordable Care Act-required needs
      assessments.
AB  - This article presents information on an Affordable Care Act-mandated community
      health needs assessment process, which brought four hospitals and a foundation in
      Pennsylvania together to imbue the assessment with community contributions.
      Community health needs assessments that engage underserved communities can be
      powerful symbols of hospitals' interest in and commitment to finding solutions.

PMID- 24583482
TI  - Working with communities to achieve health equity in Maryland's five Health
      Enterprise Zones.
AB  - This report introduces Maryland's Health Enterprise Zones (HEZ) Initiative,
      describes the efforts to establish the first HEZs, describes the principles
      fundamental to the HEZ intervention, provides an overview of their intervention
      strategies, and summarizes efforts to assess the impact of the program.

PMID- 24583484
TI  - Workforce development in Maryland to promote clinical-community connections that
      advance payment and delivery reform.
AB  - Promoting clinical-community linkages is at the heart of Maryland's efforts
      systematically to transform health care delivery, with community health workers
      (CHW) playing a central role. This article describes how Maryland is using the
      evidence-base on CHW effectiveness and training to develop a workforce capable of
      most effectively connecting communities with care.

PMID- 24583485
TI  - DC Healthy Communities Collaborative (DCHCC): a promising collaboration to reduce
      health disparities in the Nation's Capital.
AB  - SUMMARY: Fueled by community benefit requirements in the Affordable Care Act, the
      DC Healthy Communities Collaborative--a coalition of four Washington, D.C.
      hospitals and four community health centers--bridged long-standing competitive
      barriers to work together on community health improvement activities.

PMID- 24583486
TI  - Challenges and opportunities for integrating preventive substance-use-care
      services in primary care through the Affordable Care Act.
AB  - Undertreated or untreated substance use disorders (SUD) remain a pervasive,
      medically-harmful public health problem in the United States, particularly in
      medically underserved and low-income populations lacking access to appropriate
      treatment. The need for greater access to SUD treatment was expressed as policy
      in the Final Rule on standards related to essential health benefits, required to
      be covered through the 2010 Affordable Care Act (ACA) health insurance exchanges.
      SUD treatment services have been included as an essential health benefit, in a
      manner that complies with the Mental Health Parity and Addiction Equity Act
      (MHPAEA) of 2008. Consequently, with the ACA, a vast expansion of SUD-care
      services in primary care is looming. This commentary discusses challenges and
      opportunities under the ACA for equipping health care professionals with
      appropriate workforce training, infrastructure, and resources to support and
      guide science-based Screening, Brief Intervention, and Referral to Treatment
      (SBIRT) for SUD in primary care. 

PMID- 24583487
TI  - The Affordable Care Act and genetic testing for inheritable cancer syndromes:
      impact on high-risk underserved minorities.
AB  - Genetic testing for inheritable cancer syndromes is becoming a critical part of
      preventive health services. The Patient Protection and Affordable Care Act
      (PPACA) Essential Health Benefits package addresses breast cancer susceptibility
      gene testing for women who are unaffected by cancer. The absence of provisions
      for 1) men, 2) cancer patients, 3) other inheritable cancer syndromes, and 4)
      risk-reducing interventions are limitations of PPACA. We discuss provisions and
      limitations of PPACA pertaining to genetic testing and effects on high-risk
      populations, in particular minorities. The PPACA is the beginning of an ongoing
      process of incorporating genetic testing in the armamentarium of cancer
      prevention. Future efforts should focus on ensuring equitable access to genetic
      testing as a preventive service under PPACA to high-risk populations other than
      women. Consideration should also be given to provisions for risk-reducing
      interventions, especially in underserved minority populations, who are known to
      underutilize genetic testing and may have limited financial resources for medical
      intervention.

PMID- 24583488
TI  - The experiences of Massachusetts hospitals as statewide health insurance reform
      was implemented.
AB  - Hospitals treat many uninsured patients and shoulder substantial amounts of
      uncompensated care. Health reform as implemented in Massachusetts, then, would be
      expected to bode well for hospitals as many people obtain coverage from private
      and public programs. We examined changes in Massachusetts hospital payer mix,
      unreimbursed costs of care for the uninsured and those in means-tested public
      programs, and overall financial condition for the period 2004 to 2010. Despite
      increases in coverage, unreimbursed costs for the uninsured and those in means
      tested government programs did not decrease appreciably for Massachusetts
      hospitals over the study period. Major safety-net hospitals, which play a
      substantial role in serving the uninsured and Medicaid, had some initial easing
      of this burden but their financial situation weakened through 2010. The U.S.
      economic recession and Massachusetts budget pressures, which in part resulted
      from reform implementation, likely offset advantages hospitals experienced from
      reductions in the uninsured. Our analysis suggests that state actions in
      Massachusetts to change payment programs that the two major safety net hospitals
      relied on to support indigent care contributed to their financial difficulties. 

PMID- 24583489
TI  - The projected effect of the Affordable Care Act on dental care for adult Medicaid
      enrollees.
AB  - Fewer than half of all U.S. states provide dental care for non-elderly adult
      Medicaid enrollees. Although the Affordable Care Act (ACA) expands Medicaid
      eligibility for adults, states are not required to offer dental care to adults.
      We project the effect of the ACA on patient-identified barriers to dental care
      based on a framework developed using data from a 2008 survey of Minnesota
      Medicaid enrollees with and without an annual dental visit. The rate of annual
      visits (55%) was below that of all Minnesotans (79%) with 40% reporting
      difficulties accessing services. We found no racial/ethnic disparities in annual
      dental visits among adult Medicaid enrollees. Adult Medicaid recipients with no
      annual visit reported individual (51%), provider (27%), and system-level (22%)
      barriers. Hmong, Somali, and American Indian adults were more likely than others
      to report barriers to receiving dental care. We project that the ACA will not
      reduce barriers to dental care for adult Medicaid enrollees. 

PMID- 24583490
TI  - The impact of health insurance reform on insurance instability.
AB  - We investigated the impact of the 2006 Massachusetts health care reform on
      insurance coverage and stability among minority and underserved women. We
      examined 36 months of insurance claims among 1,946 women who had abnormal cancer
      screening at six community health centers pre-(2004-2005) and post-(2007-2008)
      insurance reform. We examined frequency of switches in insurance coverage as
      measures of longitudinal insurance instability. On the date of their abnormal
      cancer screening test, 36% of subjects were publicly insured and 31% were
      uninsured. Post-reform, the percent ever uninsured declined from 39% to 29% (p
      .001) and those consistently uninsured declined from 23% to 16%. To assess if
      insurance instability changed between the pre- and post-reform periods, we
      conducted Poisson regression models, adjusted for patient demographics and length
      of time in care. These revealed no significant differences from the pre- to post
      reform period in annual rates of insurance switches, incident rate ratio 0.98
      (95%- CI 0.88-1.09). Our analysis is limited by changes in the populations in the
      pre- and post-reform period and inability to capture care outside of the health
      system network. Insurance reform increased stability as measured by decreasing
      uninsured rates without increasing insurance switches. 

PMID- 24583492
TI  - Dissemination and adoption of the advanced primary care model in the Maryland
      multi-payer patient centered medical home program.
AB  - The Maryland Learning Collaborative together with the Maryland Multi-Payer
      Program transformed 52 medical practices into patient-centered medical homes
      (PCMH). The Maryland Learning Collaborative developed an Internet-based 14
      question Likert scale survey to assess the impact of the PCMH model on practices
      and providers, concerning how this new method is affecting patient care and
      outcomes. The survey was sent to 339 practitioners and 52 care management teams
      at 18 months into the program. Sixty-seven survey results were received and
      analyzed. After 18 months of participation in the PCMH initiative, participants
      demonstrated a better understanding of the PCMH initiative, improved patient
      access to care, improved care coordination, and increased health information
      technology optimization (p > .001). The findings from the survey evaluation
      suggest that practice participation in the Maryland Multi-Payer Program has
      enhanced access to care, influenced patient outcomes, improved care coordination,
      and increased use of health information technology. 

PMID- 24583491
TI  - The impact of insurance coverage during insurance reform on diagnostic resolution
      of cancer screening abnormalities.
AB  - We examined the impact of Massachusetts insurance reform on the care of women at
      six community health centers with abnormal breast and cervical cancer screening
      to investigate whether stability of insurance coverage was associated with more
      timely diagnostic resolution. We conducted Cox proportional hazards models to
      predict time from cancer screening to diagnostic resolution, examining the impact
      of 1) insurance status at time of screening abnormality, 2) number of insurance
      switches over a three-year period, and 3) insurance history over a three-year
      period. We identified 1,165 women with breast and 781 with cervical cancer
      screening abnormalities. In the breast cohort, Medicaid insurance at baseline,
      continuous public insurance, and losing insurance predicted delayed resolution.
      We did not find these effects in the cervical cohort. These data provide evidence
      that stability of health insurance coverage with insurance reform nationally may
      improve timely care after abnormal cancer screening in historically underserved
      women. 

PMID- 24583493
TI  - Reducing cancer disparities through community engagement in policy development:
      the role of cancer councils.
AB  - Cancer is the second leading cause of death in the U.S and a source of large
      racial and ethnic disparities in population health. Policy development is a
      powerful but sometimes overlooked public health tool for reducing cancer burden
      and disparities. Along with other partners in the public health system, community
      based organizations such as local cancer councils can play valuable roles in
      developing policies that are responsive to community needs and in mobilizing
      resources to support policy adoption and implementation. This paper examines the
      current and potential roles played by local cancer councils to reduce cancer
      burden and disparities. Responsive public health systems require vehicles for
      communities to engage in policy development. Cancer councils provide promising
      models of engagement. Untapped opportunities exist for enhancing policy
      development through cancer councils, such as expanding targets of engagement to
      include private-sector stakeholders and expanding methods of engagement utilizing
      the Affordable Care Act's Prevention and Public Health Fund. 

PMID- 24583494
TI  - Shaking up the dental safety-net: elimination of optional adult dental Medicaid
      benefits in California.
AB  - In July 2009, California eliminated funding for most adult non-emergency Medicaid
      dental benefits (Denti-Cal). This paper presents the findings from a qualitative
      assessment of the impacts of the Denti-Cal cuts on California's oral health
      safety-net. Interviews were conducted with dental safety-net providers throughout
      the state, including public health departments, community health centers, dental
      schools, Native American health clinics, and private providers, and were coded
      thematically using Atlas.ti. Safety-net providers reported decreased utilization
      by Denti-Cal-eligible adults, who now primarily seek emergency dental services,
      and reported shifting to focus on pediatric and privately-insured patients.
      Significant changes were reported in safety-net clinic finances, operations, and
      ability to refer. The impact of the Denti-Cal cuts has been distributed unevenly
      across the safety-net, with private providers and County Health Departments
      bearing the highest burden. 

PMID- 24583495
TI  - What can be learned from the types of community benefit programs that hospitals
      already have in place?
AB  - After implementation of the Patient Protection and Affordable Care Act (ACA) how
      will tax-exempt hospitals adjust their community benefit programs to maintain
      their non-profit status? This literature review categorized existing hospital
      based community benefit programs by reviewing published articles that met the
      following inclusion criteria: affiliated or funded by a hospital; described the
      program design; focused on community benefit or outreach; evaluated program
      outcomes; located within the United States. Of 4,917 original citations, we
      reviewed 265 full-text articles. One hundred and six (106) programs met all
      inclusion criteria and were used to develop a hospital-based community benefit
      program taxonomy. Results indicate that programs to enhance patient care, clinic
      based programs and programs with a community partner make up the majority of
      community benefit programs (25%, 28% and 31%, respectively). Few programs were
      rigorously evaluated or provide evidence of program impact. Hospitals should work
      with public health professionals to design, implement, and evaluate their
      community benefit programs. 

PMID- 24583496
TI  - 1988-1990: a look back.

PMID- 24583497
TI  - 25th Anniversary Supplement of the Journal of Health Care for the Poor and
      Underserved.

PMID- 24583498
TI  - Dose-response relationship of serum uric acid levels with risk of stroke
      mortality.
AB  - INTRODUCTION: Results from the recent meta-analysis suggested that higher serum
      uric acid (SUA) levels are positively associated with risk of stroke. However,
      the relationship of SUA levels with risk of stroke is still unclear. MATERIALS
      AND METHODS: Data from prospective cohort studies on SUA levels and risk of
      stroke mortality was used. Dose-response relationship was assessed by restricted
      cubic spline model and multivariate random effect meta-regression. RESULTS: A non
      linear relationship (Pfor non-linearity = 0.004) of SUA levels with risk of
      stroke mortality was found for men, and the relative risk (RR) with 95%
      confidence interval (CI) of stroke mortality was 1.00 (0.99-1.01), 0.99 (0.94
      1.04), 0.98 (0.91-1.06), 1.00 (0.90-1.12), 1.17 (1.09-1.24) and 1.52 (1.33-1.78)
      for 2, 3, 4, 5, 6 and 7 mg/dL of SUA levels, respectively. For women, the
      departure from linearity was not significant (Pfor non-linearity = 0.67), and the
      RR (95 %CI) of stroke mortality was 1.02 (0.99-1.04), 1.10 (0.97-1.20), 1.15
      (0.96-1.37), 1.25 (1.09-1.44), 1.39 (1.28-1.50) for 2, 3, 4, 5, 6 mg/dL of SUA
      levels, respectively. CONCLUSIONS: Different dose-response relationships of SUA
      levels with risk of stroke mortality might exist for men and for women. Dose
      response relationship of SUA levels with risk of stroke incidence needs to be
      explored.

PMID- 24583499
TI  - Monocyte subsets in coronary artery disease and their associations with markers
      of inflammation and fibrinolysis.
AB  - AIMS: The multiple roles of monocytes in atherogenesis, including inflammation,
      angiogenesis and repair are attributed to the existence of different monocyte sub
      populations. Scarce data are available on changes in phenotype and functional
      status of human monocyte subsets in patients with coronary artery disease (CAD),
      especially when monocytes are evaluated as three distinct subsets. METHODS AND
      RESULTS: Surface expression of receptors implicated in inflammation, repair and
      activation status (intracellular IKKbeta) of monocyte subsets was assessed by
      flow cytometry in 53 patients with CAD and compared to 50 age- and sex-matched
      healthy controls. Monocyte subsets were defined as CD14++CD16-CCR2+ (Mon1),
      CD14++CD16+CCR2+ (Mon2), and CD14+CD16++CCR2- (Mon3). Plasma levels of
      inflammatory cytokines (FACSArray) and fibrinolytic factors (ELISA) were measured
      in CAD. CAD was associated with reduced expression of CD14 on Mon1 (p = 0.02) and
      Mon3 (p = 0.036), higher expression of IL6 receptor on Mon1 (p = 0.025) and Mon2
      (p = 0.015), CXCR4 on Mon1 (p = 0.035) and Mon3 (p = 0.003), and CD34 on all
      subsets (all p < 0.007). Monocyte CD163 expression correlated negatively with
      interleukin (IL)-6 levels (p < 0.01 for all subsets). Expression of vascular
      endothelial growth factor receptor-1 correlated positively with plasminogen
      activator inhibitor (PAI)-1 antigen levels (r = 0.47, p = 0.006). In vitro,
      monocyte subsets derived from CAD patients showed significantly altered responses
      to endotoxin stimulation compared to monocytes from healthy controls.
      CONCLUSIONS: There is a complex interplay between phenotype and activity of
      monocytes and plasma cytokines and fibrinolytic factors. These findings support
      the presence of unique roles for the three human monocyte subsets in
      atherogenesis and CAD pathogenesis.

PMID- 24583500
TI  - Sugar sweetened beverages consumption and risk of coronary heart disease: a meta
      analysis of prospective studies.
AB  - OBJECTIVE: To summarize the evidence with respect to sugar sweetened beverages
      (SSBs) consumption and risk of coronary heart disease (CHD) and to recommend
      field standards for future analysis on this topic. METHODS: We searched for
      articles published up to February 2013 through PubMed, EMbase, and Cochrane
      Library Database and reviewed reference list of the retrieved articles.
      Prospective studies with reported relative risks (RRs) with 95% confidence
      intervals (CIs) of CHD for different categories of SSBs consumption were
      included. Random-effects models were used to evaluate the associations by
      comparing the highest and lowest categories of SSBs consumption in relation to
      risk of CHD. RESULTS: Four prospective studies with 7396 CHD cases among 173,753
      participants were included in the meta-analysis. The pooled RR (95% CI) for CHD
      in the highest category of SSBs consumption in comparison with the lowest
      category of SSBs was 1.17 (1.07-1.28). Stratified analyses indicated a
      significant association for men but not for women, with pooled RRs (95%CI) of
      1.17 (1.05-1.29) and 1.19 (0.94-1.50), respectively. For studies carried out in
      America, the pooled RR for CHD was 1.18 (1.07-1.30). Additionally, a one-severing
      per day increase in SSBs consumption was associated with a 16% increased risk of
      CHD (RR: 1.16, 95%CI: 1.10-1.23). CONCLUSION: Our meta-analysis of four studies
      suggests that consumption of SSBs may increase risk of CHD, especially among men
      and American populations. However, this finding was based on limited studies;
      further studies are warranted to critically evaluate the relationship.

PMID- 24583501
TI  - Parental perspectives on suffering and quality of life at end-of-life in children
      with advanced heart disease: an exploratory study*.
AB  - OBJECTIVE: To describe parent perspectives regarding the end-of-life experience
      of children with advanced heart disease. DESIGN: Cross-sectional multicenter
      survey study of bereaved parents. SETTING: Two tertiary care pediatric hospitals.
      SUBJECTS: Parents of children younger than 21 years with primary cardiac
      diagnoses who died in the hospital 9 months to 4 years before the survey date.
      Parents were excluded if they were non-English speakers or had previously denied
      permission to contact. INTERVENTION: The Survey for Caring for Children with
      Advanced Heart Disease was developed, piloted, and then sent to parents of all
      children who died at two sites. MEASUREMENTS AND MAIN RESULTS: Fifty bereaved
      parents responded (39% response rate) a mean of 2.7 years after their child's
      death. Median age at death was 6 months (3.6 d to 20.4 yr). At end-of-life, 86%
      of children were intubated and 46% were receiving mechanical circulatory support.
      Seventy-eight percent died during withdrawal of life-sustaining interventions and
      16% during resuscitative efforts. Parents realized that their child had no
      realistic chance of survival a median of 2 days prior to death (0-30 d).
      According to parents, 47% of children suffered "a great deal," "a lot," or
      "somewhat" during the end-of-life period. The symptoms parents perceived to be
      causing the most suffering were breathing and feeding difficulties in children
      under 2 years and fatigue and sleeping difficulties in older children. Seventy
      one percent of parents described the quality of life of their child during the
      last month of life as "poor" or "fair." Most parents (84%) described the quality
      of care delivered as "very good" or "excellent." CONCLUSIONS: According to their
      parents, many children with advanced heart disease experience suffering in the
      end-of-life care period. For most, realization that their child has no realistic
      chance of survival does not occur until late, some not until death is imminent.
      Once this realization occurs, however, parents perceive peacefulness, a "good
      death," and excellent quality of care. Strategies for improved communication
      around symptom management, quality of life, prognosis, and advance care planning
      are needed for families of children with advanced heart disease.

PMID- 24583502
TI  - The parent perspective: "being a good parent" when making critical decisions in
      the PICU.
AB  - OBJECTIVE: To identify factors important to parents making decisions for their
      critically ill child. DESIGN: Prospective cross-sectional study. SETTING: Single
      center, tertiary care PICU. SUBJECTS: Parents making critical treatment decisions
      for their child. INTERVENTION: One-on-one interviews that used the Good Parent
      Tool-2 open-ended question that asks parents to describe factors important for
      parenting their ill child and how clinicians could help them achieve their
      definition of "being a good parent" to their child. Parent responses were
      analyzed thematically. Parents also ranked themes in order of importance to them
      using the Good Parent Ranking Exercise. MEASUREMENT AND MAIN RESULTS: Of 53
      eligible parents, 43 (81%) participated. We identified nine themes through
      content analysis of the parent's narrative statements from the Good Parent Tool.
      Most commonly (60% of quotes) components of being a good parent described by
      parents included focusing on their child's quality of life, advocating for their
      child with the medical team, and putting their child's needs above their own.
      Themes key to parental decision making were similar regardless of parent race and
      socioeconomic status or child's clinical status. We identified nine clinician
      strategies identified by parents as helping them fulfill their parenting role,
      most commonly, parents wanted to be kept informed (32% of quotes). Using the Good
      Parent Ranking Exercise, fathers ranked making informed medical decisions as most
      important, whereas mothers ranked focusing on the child's health and putting
      their child's needs above their own as most important. However, mothers who were
      not part of a couple ranked making informed medical decisions as most important.
      CONCLUSION: These findings suggest a range of themes important for parents to "be
      a good parent" to their child while making critical decisions. Further studies
      need to explore whether clinician's knowledge of the parent's most valued factor
      can improve family-centered care.

PMID- 24583503
TI  - Therapeutic role of anakinra, an interleukin-1 receptor antagonist, in the
      management of secondary hemophagocytic lymphohistiocytosis/sepsis/multiple organ
      dysfunction/macrophage activating syndrome in critically ill children*.
AB  - OBJECTIVES: Secondary hemophagocytic lymphohistiocytosis, macrophage activating
      syndrome, and sepsis share the same inflammatory phenotype leading often to
      multiple organ dysfunction syndrome needing intensive care. The goal of this
      article is to describe our experience with anakinra (Kineret), a recombinant
      interleukin-1 receptor antagonist, in decreasing the systemic inflammation.
      DESIGN: Retrospective case series. SETTING: The PICU at the Helen DeVos
      Children's Hospital (Grand Rapids, MI). PATIENTS: The records of eight critically
      ill children presumed to have secondary hemophagocytic lymphohistiocytosis at our
      institution between January 1, 2011, and July 31, 2012, were reviewed.
      INTERVENTIONS: All of the patients were treated with anakinra (Kineret) and in
      some cases systemic corticosteroids as first-line therapy for secondary
      hemophagocytic lymphohistiocytosis. MEASUREMENTS AND MAIN RESULTS: Patients had a
      median age of 14 years and a median Pediatric Risk of Mortality score of 11.5.
      Four were previously healthy and four had underlying diseases that could have
      made them susceptible to secondary hemophagocytic lymphohistiocytosis.
      Indications for PICU transfer were respiratory distress 50% (4 of 8),
      cardiovascular instability 37.5% (3 of 8), and chest pain (1 of 8). Five of the
      patients (62.5%) were mechanically ventilated and 62.5% (5 of 8) received
      vasoactive infusions. Inflammatory markers were assessed linearly at the start of
      therapy and 7 days later. Baseline C-reactive protein was 206 +/- 50 mg/L (mean
      +/- SEM) at the start of anakinra and decreased by 67.1% to 68 +/- 36 mg/L (p =
      0.03). Ferritin decreased by 63.8% to 3,210 +/- 1,178 ng/mL (p = 0.30), and
      fibrinogen decreased by 42% to 158 +/- 41 mg/dL (p = 0.03). Absolute neutrophil
      count (p = 0.38) and absolute lymphocyte count (p = 0.69) did not change
      significantly. No infections were attributed to anakinra therapy. One patient
      died long after treatment with anakinra while receiving pre-hematopoietic stem
      cell transplant chemotherapy. CONCLUSIONS: Anakinra could represent a promising
      therapeutic approach in these life-threatening disorders that are likely
      underdiagnosed and often difficult to treat.

PMID- 24583504
TI  - Early goal-directed therapy in pediatric septic shock: comparison of outcomes
      "with" and "without" intermittent superior venacaval oxygen saturation
      monitoring: a prospective cohort study*.
AB  - OBJECTIVE: To evaluate the effect of intermittent central venous oxygen
      saturation monitoring (ScvO(2)) on critical outcomes in children with septic
      shock, as continuous monitoring may not be feasible in most resource-restricted
      settings. DESIGN: Prospective cohort study. SETTING: PICU of a tertiary care
      teaching hospital. PATIENTS: Consecutive children younger than 17 years with
      fluid refractory septic shock admitted to our ICU from November 2010 to October
      2012 were included. INTERVENTIONS: Enrolled children were subjected to
      subclavian/internal jugular catheter insertion. Those in whom it was successful
      formed the "exposed" group (ScvO(2) group), whereas the rest constituted the
      control group (no ScvO(2) group). In the former group, intermittent ScvO(2)
      monitoring at 1, 3, and 6 hours was used to guide resuscitation, whereas in the
      latter, only clinical variables were used. MEASUREMENTS AND MAIN RESULTS: The
      major outcomes were in-hospital mortality and achievement of therapeutic goals
      within first 6 hours. One hundred twenty children were enrolled in the study-63
      in the ScvO(2) group and 57 in the no ScvO(2) group. Baseline characteristics
      including the organ dysfunction and mortality risk scores were comparable between
      the groups. Children in the ScvO(2) group had significantly lower in-hospital
      mortality (33.3% vs 54%; relative risk, 0.61; 95% CI, 0.4, 0.93; number needed to
      treat, 5; 95% CI, 3, 27). A greater proportion of children in exposed group
      achieved therapeutic endpoints in first 6 hours (43% vs 23%, p = 0.02) and during
      entire ICU stay (71% vs 51%, p = 0.02). The mean number of dysfunctional organs
      was also significantly lesser in ScvO(2) group in comparison with no ScvO(2)
      group (2 vs 3, p < 0.001). CONCLUSION: Early goal-directed therapy using
      intermittent ScvO(2) monitoring seemed to reduce the mortality rates and improved
      organ dysfunction in children with septic shock as compared with those without
      such monitoring.

PMID- 24583506
TI  - Comparative proteomics reveals proteins impacted by nitrogen deprivation in wild
      type and high lipid-accumulating mutant strains of Tisochrysis lutea.
AB  - Understanding microalgal lipid accumulation under nitrogen starvation is of major
      interest for biomass feedstock, food and biofuel production. Using a domesticated
      oleaginous algae Tisochrysis lutea, we performed the first comparative proteomic
      analysis on the wild type strain and a selected lipid over-accumulating mutant. 2
      DE analysis was made on these strains cultured in two metabolic conditions, with
      and without nitrogen deprivation, which revealed significant differences in
      proteomes according to both strain and nitrogen availability. Mass spectrometry
      allowed us to identify 37 proteins that were differentially expressed between the
      two strains, and 17 proteins regulated by nitrogen starvation concomitantly with
      lipid accumulation. The proteins identified are known to be involved in various
      metabolic pathways including lipid, carbohydrate, amino acid, energy and pigment
      metabolisms, photosynthesis, protein translation, stress response and cell
      division. Four candidates were selected for possible implication in the over
      accumulation of lipids during nitrogen starvation. These include the plastid beta
      ketoacyl-ACP reductase protein, the coccolith scale associated protein and two
      glycoside hydrolases involved in biosynthesis of fatty acids, carbon homeostasis
      and carbohydrate catabolism, respectively. This proteomic study confirms the
      impact of nitrogen starvation on overall metabolism and provides new perspectives
      to study the lipid over-accumulation in the prymnesiophyte haptophyte T. lutea.
      BIOLOGICAL SIGNIFICANCE: This paper study consists of the first proteomic
      analysis on Tisochrysis lutea, a non-model marine microalga of interest for
      aquaculture and lipids production. Comparative proteomics revealed proteins
      putatively involved in the up-accumulation of neutral lipids in a mutant strain
      during nitrogen starvation. The results are of great importance for future works
      to improve lipid accumulation in microalgae of biotechnological interest for
      biofuel production. This article is part of a Special Issue entitled: Proteomics
      of non-model organisms.

PMID- 24583505
TI  - Safety of sildenafil in infants*.
AB  - OBJECTIVE: In view of the recent U.S. Food and Drug Administration's warning
      against the use of sildenafil in pediatric patients, we aimed to provide an
      updated overview of the dosing and safety of sildenafil in infants and to explore
      the relevance of the present safety concerns to the infant population. DATA
      SOURCE: The National Library of Medicine PubMed and Cochrane Database of
      Systematic Reviews were searched using the following terms: Sildenafil AND
      (infant OR infants OR newborn OR newborns OR child OR children OR childhood OR
      pediatric OR pediatrics OR paediatric OR paediatrics). STUDY SELECTION: Studies
      presenting original clinical data regarding the dosing, use, or safety of
      sildenafil in infants with pulmonary hypertension would be included. DATA
      EXTRACTION: Of the 49 included studies, case reports and case series were the
      most common type of publications (n = 25). The identified trials included 625
      children, with more than 140 infants. Persistent pulmonary hypertension of the
      newborn and pulmonary hypertension associated with other conditions were the most
      common underlying diagnoses. CONCLUSION: There is currently no evidence of
      serious adverse event in infants exposed to sildenafil. Present safety concerns
      regarding the use of sildenafil in pediatric patients should be further explored
      before being applied to infant population. Sildenafil remains a valuable option
      for the treatment of pulmonary hypertension in young infants. Prospective studies
      should be designed in such a way that they include a safety assessment to
      evaluate potential adverse outcomes of sildenafil therapy in this population.

PMID- 24583507
TI  - Immunological profile of antivenoms: preclinical analysis of the efficacy of a
      polyspecific antivenom through antivenomics and neutralization assays.
AB  - Parenteral administration of animal-derived antivenoms constitutes the mainstay
      in the treatment of snakebite envenomings. Despite the fact that this therapy has
      been available for over a century, the detailed understanding of the neutralizing
      and immunoreactivity profiles of the majority of antivenoms is pending.
      Currently, a combination of preclinical neutralization tests and 'antivenomics',
      i.e. a proteomic-based assessment of antivenom immunoreactivity, provides a
      powerful analytical platform to investigate the preclinical efficacy of
      antivenoms. In this review, the studies performed on the polyvalent antivenom
      manufactured by Instituto Clodomiro Picado, Costa Rica, are summarized. This
      antivenom is prepared by immunizing horses with a mixture of the venoms of
      Bothrops asper, Crotalus simus and Lachesis stenophrys, and is used in Central
      America for the treatment of envenomings by viperid species. Overall, the
      antivenom shows a widespread pattern of immunological reactivity against
      homologous and heterologous venoms, which correlates with its ability to
      neutralize lethal, hemorrhagic, myotoxic, coagulant, defibrinogenating,
      phospholipase A2 and proteinase activities of viperid venoms. At the same time,
      antivenomics detected several venom components against which the antivenom shows
      only partial or negligible immunorecognition, such as low molecular mass
      vasoactive peptides, disintegrins, and some phospholipases A2, P-I
      metalloproteinases and serine proteinases. Such information can be used to design
      strategies for enhancing the antibody response of horses against poorly
      immunogenic, toxicologically-relevant venom components in order to further
      improve the efficacy of this antivenom. BIOLOGICAL SIGNIFICANCE: The timely
      parenteral administration of an appropriate antivenom remains, more than a
      century after the development of the first serum antivenimeux by Calmette and
      Phisalix and Bertrand, the only currently effective treatment for snakebite
      envenomings. A key technical issue in the generation of novel antivenoms is the
      design of optimized immunization venom mixtures that ensure that the resulting
      antidotes will be effective against the highest number of venoms from snakes of
      medical concern across the geographical range where they will be used.
      Antivenomics is a proteomics-based protocol developed to complement in vitro and
      in vivo standard preclinical tests in the qualitative and quantitative
      characterization of the immunological profile and the extent of cross-reactivity
      of antivenoms against homologous and heterologous venoms. Antivenomics is
      translational venomics. The combination of antivenomics and neutralization assays
      represents a powerful analytical platform to investigate the efficacy of
      antivenoms at the molecular and preclinical levels. This article is part of a
      Special Issue entitled: Proteomics of non-model organisms.

PMID- 24583508
TI  - Image enhancement using MCNP5 code and MATLAB in neutron radiography.
AB  - This work presents a method that can be used to enhance the neutron radiography
      (NR) image for objects with high scattering materials like hydrogen, carbon and
      other light materials. This method used Monte Carlo code, MCNP5, to simulate the
      NR process and get the flux distribution for each pixel of the image and
      determines the scattered neutron distribution that caused image blur, and then
      uses MATLAB to subtract this scattered neutron distribution from the initial
      image to improve its quality. This work was performed before the commissioning of
      digital NR system in Jan. 2013. The MATLAB enhancement method is quite a good
      technique in the case of static based film neutron radiography, while in neutron
      imaging (NI) technique, image enhancement and quantitative measurement were
      efficient by using ImageJ software. The enhanced image quality and quantitative
      measurements were presented in this work. 

PMID- 24583509
TI  - A simple and efficient method of nickel electrodeposition for the cyclotron
      production of (64)Cu.
AB  - Nickel targets for the cyclotron production of (64)Cu were prepared by
      electrodeposition on a gold backing from nickel chloride solutions using boric
      acid as buffer. Parameters studied were nickel chloride and boric acid
      concentration, temperature and current density. All plating conditions studied
      were successful obtaining efficiencies of approximately 90% in 2-3 h, reaching
      almost quantitative plating (>97%) in 10-20 h depending on the current density.
      All plated targets withstood proton irradiations up to 40 uA for 2 h. Recovered
      nickel was successfully recycled and reused with an overall efficiency >95%.

PMID- 24583510
TI  - Evaluation of occupational cold environments: field measurements and subjective
      analysis.
AB  - The present work is dedicated to the study of occupational cold environments in
      food distribution industrial units. Field measurements and a subjective
      assessment based on an individual questionnaire were considered. The survey was
      carried out in 5 Portuguese companies. The field measurements include 26
      workplaces, while a sample of 160 responses was considered for the subjective
      assessment. In order to characterize the level of cold exposure, the Required
      Clothing Insulation Index (IREQ) was adopted. The IREQ index highlights that in
      the majority of the workplaces the clothing ensembles worn are inadequate, namely
      in the freezing chambers where the protection provided by clothing is always
      insufficient. The questionnaires results show that the food distribution sector
      is characterized by a female population (70.6%), by a young work force (60.7% are
      less than 35 yr old) and by a population with a medium-length professional career
      (80.1% in this occupation for less than 10 yr). The incidence of health effects
      which is higher among women, the distribution of protective clothing (50.0% of
      the workers indicate one garment) and the significant percentage of workers
      (>75%) that has more difficulties in performing the activity during the winter
      represent other important results of the present study. 

PMID- 24583511
TI  - Comparison of nanoparticle exposures between fumed and sol-gel nano-silica
      manufacturing facilities.
AB  - Silica nanoparticles (SNPs) are widely used all around the world and it is
      necessary to evaluate appropriate risk management measures. An initial step in
      this process is to assess worker exposures in their current situation. The
      objective of this study was to compare concentrations and morphologic
      characteristics of fumed (FS) and sol-gel silica nanoparticles (SS) in two
      manufacturing facilities. The number concentration (NC) and particle size were
      measured by a real-time instrument. Airborne nanoparticles were subsequently
      analyzed using a TEM/EDS. SNPs were discharged into the air only during the
      packing process, which was the last manufacturing step in both the manufacturing
      facilities studied. In the FS packing process, the geometric mean (GM) NC in the
      personal samples was 57,000 particles/cm(3). The geometric mean diameter (GMD)
      measured by the SMPS was 64 nm. Due to the high-temperature formation process,
      the particles exhibited a sintering coagulation. In the SS packing process that
      includes a manual jet mill operation, the GM NC was calculated to be 72,000
      particles/cm(3) with an assumption of 1,000,000 particles/cm(3) when the upper
      limit is exceeded (5% of total measure). The particles from SS process had a
      spherical-shaped morphology with GMD measured by SMPS of 94 nm. 

PMID- 24583512
TI  - Work-related stress management by Finnish enterprises.
AB  - Work-related stress has become one of the major problems in working societies and
      it increases employees' risk of disease. Its importance has been emphasized also
      due to its' great socio-economic consequences. Different stress management and
      worksite interventions have been implemented, however, the actual practices in
      companies have been assessed little. The purpose of this study was to examine how
      enterprises in Finland manage work-related stress. An assessment of work-related
      stress methods was conducted in 40 enterprises acting in the metropolitan area of
      Finland in May 2010 by a questionnaire. The concept of work-related stress was
      well known by participants. Enterprises rarely had their own work-related stress
      management protocol even though all of the workplaces had experienced work
      related stress at some point. The collaboration between the workplace and
      occupational health services varied. Companies easily placed the responsibility
      for work-related stress assessment and handling on occupational health services.
      Workplaces have to pay more attention to work-related stress and related issues.
      The easiest way to do this is to collaborate with occupational health services.
      Protocols for collaboration should be developed jointly using the available
      models which have been established as cost-effective. 

PMID- 24583513
TI  - Flow characteristics and robustness of an inclined quad-vortex range hood.
AB  - A novel design of range hood, which was termed the inclined quad-vortex (IQV)
      range hood, was examined for its flow and containment leakage characteristics
      under the influence of a plate sweeping across the hood face. A flow
      visualization technique was used to unveil the flow behavior. Three
      characteristic flow modes were observed: convex, straight, and concave modes. A
      tracer gas detection method using sulfur hexafluoride (SF6) was employed to
      measure the containment leakage levels. The results were compared with the test
      data reported previously in the literature for a conventional range hood and an
      inclined air curtain (IAC) range hood. The leakage SF6 concentration of the IQV
      range hood under the influence of the plate sweeping was 0.039 ppm at a suction
      flow rate of 9.4 m(3)/min. The leakage concentration of the conventional range
      hood was 0.768 ppm at a suction flow rate of 15.0 m(3)/min. For the IAC range
      hood, the leakage concentration was 0.326 ppm at a suction flow rate of 10.9
      m(3)/min. The IQV range hood presented a significantly lower leakage level at a
      smaller suction flow rate than the conventional and IAC range hoods due to its
      aerodynamic design for flow behavior. 

PMID- 24583514
TI  - Does living and working in a hot environment induce clinically relevant changes
      in immune function and voluntary force production capacity?
AB  - This study investigated the effect of living (summer vs. winter) and working
      (morning vs. afternoon) in a hot environment on markers of immune function and
      forearm strength. Thirty-one healthy male gas field employees were screened
      before (between 05:30 and 07:00) and after their working day (between 15:30 and
      17:00) during both seasons. Body core temperature and physical activity were
      recorded throughout the working days. The hot condition (i.e. summer) led a
      higher (p<=0.05) average body core temperature (~37.2 vs. ~37.4  degrees C) but
      reduced physical activity (-14.8%) during the work-shift. Our data showed an
      increase (p<=0.05) in lymphocyte and monocyte counts in the summer. Additionally,
      work-shift resulted in significant (p<=0.001) changes in leukocytes, lymphocytes
      and monocytes independently of the environment. Handgrip (p=0.069) and pinch
      (p=0.077) forces tended to be reduced from pre-to post-work, while only force
      produced during handgrip manoeuvres was significantly reduced (p<=0.05) during
      the hot compared to the temperate season. No interactions were observed between
      the environment and work-shift for any marker of immune function or forearm
      strength. In summary, working and living in hot conditions impact on markers of
      immune function and work capacity; however by self-regulating energy expenditure,
      immune markers remained in a healthy reference range. 

PMID- 24583516
TI  - Piezoelectric crystals generate NMR-like signals for rapid spectrometer
      troubleshooting.
AB  - Use of frequency-control quartz crystals for the generation of NMR-like signals
      via the piezoelectric effect is discussed. Such crystals are inexpensive and
      cover a wide range of RF frequencies. The crystal is connected to the
      spectrometer through a 30dB attenuator. Excitation by single, short RF pulses
      results in time domain signals similar to NMR FIDs. We show that the crystal
      should be shunted by a low resistance for largest Q (longest T2). By using odd
      higher overtones, the crystals were made to resonate at the high operating
      frequencies typical of modern spectrometers, here up to 630MHz. The performance
      of precision manufactured crystals is particularly better at high frequencies,
      compared to mass production crystals. The abundant and stable signal provided by
      the piezoelectric crystals yields a simple method for troubleshooting and testing
      NMR spectrometers. 

PMID- 24583515
TI  - Prevalence of occupational allergy in medical researchers exposed to laboratory
      animals.
AB  - Allergy to laboratory animals is a well known occupational hazard and remains a
      health concern for individuals in contact with lab animals. This study evaluates
      the prevalence of allergy symptoms among medical researchers exposed to
      laboratory animals. We analyzed data from a cross-sectional survey, involving
      subjects (n=169, 21-59 yr), working in Kochi Medical School, Japan. They were
      asked to fill out a questionnaire to evaluate symptoms related to contact with
      laboratory animals. The overall response rate was 86.2%. The prevalence of
      laboratory animal allergy was 17.6%. The symptoms most reported were allergic
      rhino-conjunctivitis and asthma. A small number of the subjects received
      education on the allergy issue and 62.5% of subjects with an allergy to
      laboratory animals claimed to have atopy. Protection from animal allergens should
      be a high priority for institutions using lab animals; providing continuous
      education to animal handlers would be meaningful to reduce and control exposure. 

PMID- 24583517
TI  - Fast and robust measurement of microstructural dimensions using temporal
      diffusion spectroscopy.
AB  - Mapping axon sizes non-invasively is of interest for neuroscientists and may have
      significant clinical potential because nerve conduction velocity is directly
      dependent on axon size. Current approaches to measuring axon sizes using
      diffusion-weighted MRI, e.g. q-space imaging with pulsed gradient spin echo
      (PGSE) sequences usually require long scan times and high q-values to detect
      small axons (diameter <2MUm). The oscillating gradient spin echo (OGSE) method
      has been shown to be able to achieve very short diffusion times and hence may be
      able to detect smaller axons with high sensitivity. In the current study, OGSE
      experiments were performed to measure the inner diameters of hollow
      microcapillaries with a range of sizes (~1.5-19.3MUm) that mimic axons in the
      human central nervous system. The results suggest that OGSE measurements, even
      with only moderately high frequencies, are highly sensitive to compartment sizes,
      and a minimum of two ADC values with different frequencies may be sufficient to
      extract the microcapillary size accurately. This suggests that the OGSE method
      may serve as a fast and robust measurement method for mapping axon sizes non
      invasively. 

PMID- 24583518
TI  - Groundwater source contamination mechanisms: physicochemical profile clustering,
      risk factor analysis and multivariate modelling.
AB  - An integrated domestic well sampling and "susceptibility assessment" programme
      was undertaken in the Republic of Ireland from April 2008 to November 2010.
      Overall, 211 domestic wells were sampled, assessed and collated with local
      climate data. Based upon groundwater physicochemical profile, three clusters have
      been identified and characterised by source type (borehole or hand-dug well) and
      local geological setting. Statistical analysis indicates that cluster membership
      is significantly associated with the prevalence of bacteria (p=0.001), with mean
      Escherichia coli presence within clusters ranging from 15.4% (Cluster-1) to 47.6%
      (Cluster-3). Bivariate risk factor analysis shows that on-site septic tank
      presence was the only risk factor significantly associated (p<0.05) with
      bacterial presence within all clusters. Point agriculture adjacency was
      significantly associated with both borehole-related clusters. Well design
      criteria were associated with hand-dug wells and boreholes in areas characterised
      by high permeability subsoils, while local geological setting was significant for
      hand-dug wells and boreholes in areas dominated by low/moderate permeability
      subsoils. Multivariate susceptibility models were developed for all clusters,
      with predictive accuracies of 84% (Cluster-1) to 91% (Cluster-2) achieved. Septic
      tank setback was a common variable within all multivariate models, while
      agricultural sources were also significant, albeit to a lesser degree.
      Furthermore, well liner clearance was a significant factor in all models,
      indicating that direct surface ingress is a significant well contamination
      mechanism. Identification and elucidation of cluster-specific contamination
      mechanisms may be used to develop improved overall risk management and wellhead
      protection strategies, while also informing future remediation and maintenance
      efforts. 

PMID- 24583519
TI  - Comparison of VFA titration procedures used for monitoring the biogas process.
AB  - Titrimetric determination of volatile fatty acids (VFAs) contents is a common way
      to monitor a biogas process. However, digested manure from co-digestion biogas
      plants has a complex matrix with high concentrations of interfering components,
      resulting in varying results when using different titration procedures.
      Currently, no standardized procedure is used and it is therefore difficult to
      compare the performance among plants. The aim of this study was to evaluate four
      titration procedures (for determination of VFA-levels of digested manure samples)
      and compare results with gas chromatographic (GC) analysis. Two of the procedures
      are commonly used in biogas plants and two are discussed in literature. The
      results showed that the optimal titration results were obtained when 40 mL of
      four times diluted digested manure was gently stirred (200 rpm). Results from
      samples with different VFA concentrations (1-11 g/L) showed linear correlation
      between titration results and GC measurements. However, determination of VFA by
      titration generally overestimated the VFA contents compared with GC measurements
      when samples had low VFA concentrations, i.e. around 1 g/L. The accuracy of
      titration increased when samples had high VFA concentrations, i.e. around 5 g/L.
      It was further found that the studied ionisable interfering components had lowest
      effect on titration when the sample had high VFA concentration. In contrast,
      bicarbonate, phosphate and lactate had significant effect on titration accuracy
      at low VFA concentration. An extended 5-point titration procedure with pH
      correction was best to handle interferences from bicarbonate, phosphate and
      lactate at low VFA concentrations. Contrary, the simplest titration procedure
      with only two pH end-points showed the highest accuracy among all titration
      procedures at high VFA concentrations. All in all, if the composition of the
      digested manure sample is not known, the procedure with only two pH end-points
      should be the procedure of choice, due to its simplicity and accuracy. 

PMID- 24583520
TI  - Combined use of delta(13)C, delta(15)N, and delta(34)S tracers to study anaerobic
      bacterial processes in groundwater flow systems.
AB  - We present an approach for determining the major anaerobic bacterial processes in
      aquifers, using the combined stable isotope ratios of major elements (C, N, and
      S) as net recorders of the biogeochemical reactions. The Kumamoto groundwater is
      constituted of two major flow systems, A-A' and B-B', within 10(3) km-scale area.
      Previous study [Hosono, T., Tokunaga, T., Kagabu, M., Nakata, H., Orishikida, T.,
      Lin, I-T., Shimada, J., 2013. The use of delta(15)N and delta(18)O tracers with
      an understanding of groundwater flow dynamics for evaluating the origins and
      attenuation mechanisms of nitrate pollution. Water Res. 47, 2661-2675.]
      investigated the nitrate sources and extent of denitrification using [Formula:
      see text] and [Formula: see text] tracers. In the present study, we studied a
      type of denitrification (heterogenic vs. autotrophic) and occurrence of
      sequential anaerobic processes along the flow systems with newly measured
      delta(13)CDIC and [Formula: see text] . In A-A' flow system, C, N, and S isotopic
      compositions did not change along the flow direction. However, in B-B' flow
      system significant sulfate reduction (with a maximum [Formula: see text]
      enrichment of +550/00) occurred along with denitrification (with a maximum
      [Formula: see text] enrichment of +380/00) as the groundwater flowed down
      gradient. Depletions in [Formula: see text] (-80/00 maximum) were found only
      sporadically. These observations imply that autotrophic denitrification could
      occur in very limited parts of the study area. Moreover, the occurrence of
      methanogenic reactions was suggested by the enriched delta(13)CDIC signature
      (+80/00 maximum) at a denitrification hotspot. By characterizing C, N, and S
      isotope compositional changes in wide redox range (from aerobic oxidation of
      organic carbon, through denitrification, to sulfate reduction, until
      methanogenesis), we could develop the model of C, N, and S isotopic evolutional
      patterns under different redox scenarios. Proposed model is useful in obtaining a
      comprehensive understanding of the major anaerobic bacterial processes in aquifer
      systems, including distinguishing between heterotrophic and autotrophic
      denitrification. 

PMID- 24583521
TI  - Electrochemical struvite precipitation from digestate with a fluidized bed
      cathode microbial electrolysis cell.
AB  - Microbial electrolysis cells (MECs) can be used to simultaneously convert
      wastewater organics to hydrogen and precipitate struvite, but scale formation at
      the cathode surface can block catalytic active sites and limit extended
      operation. To promote bulk phase struvite precipitation and minimize cathode
      scaling, a two-chamber MEC was designed with a fluidized bed to produce suspended
      particles and inhibit scale formation on the cathode surface. MEC operation
      elevated the cathode pH to between 8.3 and 8.7 under continuous flow conditions.
      Soluble phosphorus removal using digester effluent ranged from 70 to 85% with
      current generation, compared to 10-20% for the control (open circuit conditions).
      At low current densities (<=2 mA/m(2)), scouring of the cathode by fluidized
      particles prevented scale accumulation over a period of 8 days. There was nearly
      identical removal of soluble phosphorus and magnesium from solution, and an
      equimolar composition in the collected solids, supporting phosphorus removal by
      struvite formation. At an applied voltage of 1.0 V, energy consumption from the
      power supply and pumping (0.2 Wh/L, 7.5 Wh/g-P) was significantly less than that
      needed by other struvite formation methods based on pH adjustment such as
      aeration and NaOH addition. In the anode chamber, current generation led to COD
      oxidation (1.1-2.1 g-COD/L-d) and ammonium removal (7-12 mM) from digestate
      amended with 1 g/L of sodium acetate. These results indicate that a fluidized bed
      cathode MEC is a promising method of sustainable electrochemical nutrient and
      energy recovery method for nutrient rich wastewaters. 

PMID- 24583522
TI  - Source identification of high glyme concentrations in the Oder River.
AB  - The objective of the following study was to identify the source of high
      concentrations of glycol diethers (diglyme, triglyme, and tetraglyme) in the Oder
      River. Altogether four sampling campaigns were conducted and over 50 surface
      samples collected. During the first two samplings of the Oder River in the
      Oderbruch region (km 626-690), glymes were detected at concentrations reaching
      0.065 MUg L(-1) (diglyme), 0.54 MUg L(-1) (triglyme) and 1.7 MUg L(-1)
      (tetraglyme). The subsequent sampling of the Oder River, from the area close to
      the source to the Poland-Germany border (about 500 km) helped to identify the
      possible area of the dominating glyme entry into the river between km 310 and km
      331. During that sampling, the maximum concentration of triglyme was 0.46 MUg L(
      1) and tetraglyme 2.2 MUg L(-1); diglyme was not detected. The final sampling
      focused on the previously identified area of glyme entry, as well as on
      tributaries of the Oder River. Samples from Czarna Woda stream and Kaczawa River
      contained even higher concentrations of diglyme, triglyme, and tetraglyme,
      reaching 5.2 MUg L(-1), 13 MUg L(-1) and 81 MUg L(-1), respectively. Finally,
      three water samples were analyzed from a wastewater treatment plant receiving
      influents from a Copper Smelter and Refinery; diglyme, triglyme, and tetraglyme
      were present at a maximum concentration of 1700 MUg L(-1), 13,000 MUg L(-1), and
      190,000 MUg L(-1), respectively. Further research helped to identify the source
      of glymes in the wastewater. The gas desulfurization process Solinox uses a
      mixture of glymes (Genosorb((r))1900) as a physical absorption medium to remove
      sulfur dioxide from off-gases from the power plant. The wastewater generated from
      the process and from the maintenance of the equipment is initially directed to
      the wastewater treatment plant where it undergoes mechanical and chemical
      treatment processes before being discharged to the tributaries of the Oder River.
      Although monoglyme was also analyzed, it was not detected in any of the water
      samples. 

PMID- 24583523
TI  - Dissolved organic nitrogen and its biodegradable portion in a water treatment
      plant with ozone oxidation.
AB  - Biodegradability of dissolved organic nitrogen (DON) has been studied in
      wastewater, freshwater and marine water but not in drinking water. Presence of
      biodegradable DON (BDON) in water prior to and after chlorination may promote
      formation of nitrogenous disinfectant by-products and growth of microorganisms in
      the distribution system. In this study, an existing bioassay to determine BDON in
      wastewater was adapted and optimized, and its application was tested on samples
      from four treatment stages of a water treatment plant including ozonation and
      biologically active filtration. The optimized bioassay was able to detect BDON in
      50 MUg L(-1) as N of glycine and glutamic solutions. BDON in raw (144-275 MUg L(
      1) as N), softened (59-226 MUg L(-1) as N), ozonated (190-254 MUg L(-1) as N),
      and biologically filtered (17-103 MUg L(-1) as N) water samples varied over a
      sampling period of 2 years. The plant on average removed 30% of DON and 68% of
      BDON. Ozonation played a major role in increasing the amount of BDON (31%) and
      biologically active filtration removed 71% of BDON in ozonated water. 

PMID- 24583524
TI  - Insights into the relationship between antimicrobial residues and bacterial
      populations in a hospital-urban wastewater treatment plant system.
AB  - The relationship between antimicrobial residues, antibiotic resistance prevalence
      and bacterial community composition in hospital effluent and in the receiving
      wastewater treatment plant was studied. Samples from hospital effluent, raw
      inflow and final effluent of the receiving wastewater treatment plant were
      characterized for amoxicillin and ciprofloxacin resistance prevalence, content of
      heavy metals and antimicrobial residues and bacterial community structure, based
      on 16S rRNA gene PCR-DGGE analysis. The concentration of fluoroquinolones,
      arsenic and mercury was in general higher in hospital effluent than in raw
      inflow, while the opposite was observed for tetracyclines, sulfonamides and
      penicillin G. The prevalence of ciprofloxacin resistance was significantly higher
      in hospital effluent than in raw inflow. The concentration of antimicrobial
      residues was observed to be significantly correlated with the prevalence of
      antibiotic resistant bacteria and with variations in the bacterial community.
      Hospital effluent was confirmed as a relevant, although not unique, source of
      antimicrobial residues and antibiotic resistant bacteria to the wastewater
      treatment plant. Moreover, given the high loads of antibiotic residues and
      antibiotic resistant bacteria that may occur in hospital effluents, these
      wastewater habitats may represent useful models to study and predict the impact
      of antibiotic residues on bacterial communities. 

PMID- 24583525
TI  - Textile wastewater treatment: aerobic granular sludge vs activated sludge
      systems.
AB  - Textile effluents are characterised by high content of recalcitrant compounds and
      are often discharged (together with municipal wastewater to increase their
      treatability) into centralized wastewater treatment plants with a complex
      treatment scheme. This paper reports the results achieved adopting a granular
      sludge system (sequencing batch biofilter granular reactor - SBBGR) to treat
      mixed municipal-textile wastewater. Thanks to high average removals in SBBGR
      (82.1% chemical oxygen demand, 94.7% total suspended solids, 87.5% total Kjeldahl
      nitrogen, 77.1% surfactants), the Italian limits for discharge into a water
      receiver can be complied with the biological stage alone. The comparison with the
      performance of the centralized plant treating the same wastewater has showed that
      SBBGR system is able to produce an effluent of comparable quality with a simpler
      treatment scheme, a much lower hydraulic residence time (11 h against 30 h) and a
      lower sludge production. 

PMID- 24583526
TI  - Asymmetric carbon nanotube-MnO2 two-ply yarn supercapacitors for wearable
      electronics.
AB  - Strong and flexible two-ply carbon nanotube yarn supercapacitors are electrical
      double layer capacitors that possess relatively low energy storage capacity.
      Pseudocapacitance metal oxides such as MnO2 are well known for their high
      electrochemical performance and can be coated on carbon nanotube yarns to
      significantly improve the performance of two-ply carbon nanotube yarn
      supercapacitors. We produced a high performance asymmetric two-ply yarn
      supercapacitor from as-spun CNT yarn and CNT@Mn22 composite yarn in aqueous
      electrolyte. The as-spun CNT yarn serves as negative electrode and the CNT@MnO2
      composite yarn as positive electrode. This asymmetric architecture allows the
      operating potential window to be extended from 1.0 to 2.0 V and results in much
      higher energy and power densities than the reference symmetric two-ply yarn
      supercapacitors, reaching 42.0 Wh kg(-1) at a lower power density of 483.7 W kg(
      1), and 28.02 Wh kg(-1) at a higher power density of 19,250 W kg(-1). The
      asymmetric supercapacitor can sustain cyclic charge-discharge and repeated
      folding/unfolding actions without suffering significant deterioration of specific
      capacitance. The combination of high strength, flexibility and electrochemical
      performance makes the asymmetric two-ply yarn supercapacitor a suitable power
      source for flexible electronic devices for applications that require high
      durability and wearer comfort.

PMID- 24583527
TI  - Carbohydrate-based Cu(I) stabilizing ligands and their use in the synthesis of
      carbohydrate-ferrocene conjugates.
AB  - A series of carbohydrate-ferrocene conjugates have been synthesized by copper(I)
      catalyzed cycloaddition of carbohydrate-azides and ethynylferrocene (CuAAC).
      Newly carbohydrate-based tris-triazoles have been used as Cu(I) stabilizing
      ligands and showed at least comparable, in some cases even better results
      compared to the use of tris-(benzyltriazolylmethyl)amine (TBTA). 

PMID- 24583528
TI  - Multiple MU-stability of neural networks with unbounded time-varying delays.
AB  - In this paper, we are concerned with a class of recurrent neural networks with
      unbounded time-varying delays. Based on the geometrical configuration of
      activation functions, the phase space R(n) can be divided into several Phieta
      type subsets. Accordingly, a new set of regions Omegaeta are proposed, and
      rigorous mathematical analysis is provided to derive the existence of equilibrium
      point and its local MU-stability in each Omegaeta. It concludes that the n
      dimensional neural networks can exhibit at least 3(n) equilibrium points and 2(n)
      of them are MU-stable. Furthermore, due to the compatible property, a set of new
      conditions are presented to address the dynamics in the remaining 3(n)-2(n)
      subset regions. As direct applications of these results, we can get some criteria
      on the multiple exponential stability, multiple power stability, multiple log
      stability, multiple log-log-stability and so on. In addition, the approach and
      results can also be extended to the neural networks with K-level nonlinear
      activation functions and unbounded time-varying delays, in which there can store
      (2K+1)(n) equilibrium points, (K+1)(n) of them are locally MU-stable. Numerical
      examples are given to illustrate the effectiveness of our results. 

PMID- 24583529
TI  - Patient dies after judge gives UK hospital trust permission to withhold blood
      products.

PMID- 24583530
TI  - Proposed US food labels would highlight calories, added sugars, and serving
      sizes.

PMID- 24583531
TI  - Morecambe Bay trust is criticised for lack of openness about complaints.

PMID- 24583533
TI  - Expression of CD25 antigen on CD34+ cells is an independent predictor of outcome
      in late-stage MDS patients treated with azacitidine.

PMID- 24583534
TI  - Incidence and prognostic significance of karyotypic subgroups in older patients
      with acute myeloid leukemia: the Swedish population-based experience.
AB  - The Swedish population-based acute myeloid leukemia registry contains data from
      3251 patients (excluding acute promyelocytic leukemia) diagnosed between 1997 and
      2006. Informative cytogenetic data from 1893 patients were retrospectively added,
      including 1054 patients aged between 60 and 79 years. Clonal abnormalities were
      found in 57% of the informative karyotypes. Karyotypic patterns differed by age:
      t(8;21), inv(16) and t(11q23) were more common in younger patients, whereas loss
      of 5q, 7q and 17p, monosomal karyotype (MK) and complex karyotypes were more
      common in older patients. Loss of 5q, 7q and 17p often occurred together within
      MK. Patients with ?5 chromosome abnormalities had worse overall survival than
      those with fewer abnormalities or normal karyotype in all age groups. Loss of 5q,
      7q and/or 17p had, in contrast to MK, a further negative impact on survival.
      Multivariable Cox regression analyses on risk factors in patients <80 years with
      cytogenetic abnormalities and intensive treatment revealed that age and
      performance status had the most significant impact on survival (both P<0.001),
      followed by sex (P=0.0135) and a karyotype including -7/del(7q) (P=0.048). 

PMID- 24583536
TI  - Effects of treadmill training on combined goserelin acetate and doxorubicin
      induced osteopenia in female rats.
AB  - OBJECTIVES: This study examined individual and combined effects of the cancer
      treatments goserelin acetate (GA) and doxorubicin (DOX) on bone and determined if
      treadmill running (TM) provides osteoprotection. METHODS: Ten-week-old female
      Sprague-Dawley rats were randomly assigned to sedentary (SED) or TM groups. SED
      received GA, DOX, combined GA and DOX (GA+DOX), or placebo and maintained normal
      cage activity. TM received GA, DOX, GA+DOX, or placebo and participated in a
      progressive motorized treadmill protocol. After 8 weeks, tibiae were evaluated
      using micro computed tomography. RESULTS: Negative drug effects were observed in
      cancellous bone (bone volume/tissue volume, trabecular number, trabecular
      thickness, trabecular spacing; P<0.05). An additive bone volume/tissue volume and
      trabecular spacing effect was observed in SED GA+DOX (vs. SED+GA and SED+DOX,
      P<0.05) but not in TM GA+DOX (vs. TM+GA and TM+DOX, P>0.05). Negative drug
      effects were observed in cortical bone (cross-sectional volume, cortical volume,
      marrow volume; P<0.05), but combined GA+DOX did not exacerbate these effects.
      Additionally, there were no protective cortical bone effects observed in TM.
      CONCLUSIONS: Combined GA+DOX exacerbates cancellous osteopenia in the tibia, and
      treadmill running provided only minor protection.

PMID- 24583535
TI  - Altered bone development in a mouse model of peripheral sensory nerve
      inactivation.
AB  - OBJECTIVES: The present study sought to determine the effects of decreased
      peripheral sensory nerve function on skeletal development and bone metabolism in
      mice. METHODS: C57BL/6 neonatal mice were treated with capsaicin to induce
      peripheral sensory nerve degeneration, and compared to vehicle-treated controls
      at 4, 8 and 12 weeks of age. Changes in bone structure were assessed using micro
      computed tomography, mechanical properties and fracture resistance were assessed
      using three-point bending of radii, and bone turnover was assessed using dynamic
      histomorphometry and serum biomarkers. RESULTS: Capsaicin treatment resulted in
      small but significant decreases in bone structure, particularly affecting
      trabecular bone. Capsaicin-treated mice exhibited lower trabecular thickness at
      the femoral metaphysis and L5 vertebral body compared with vehicle-treated mice.
      However, capsaicin- and vehicle-treated mice had similar mechanical properties
      and bone turnover rates. CONCLUSION: Neonatal capsaicin treatment affected
      trabecular bone during development; however these small changes may not be
      meaningful with respect to bone strength under normal loading conditions. It is
      possible that capsaicin-sensitive neurons may be more important for bone under
      stress conditions such as increased mechanical loading or injury. Future studies
      will investigate this potential role of peripheral sensory nerves in bone
      adaptation.

PMID- 24583537
TI  - Prevalence and risk-factors of neurogenic heterotopic ossification in traumatic
      spinal cord and traumatic brain injured patients admitted to specialised units in
      Australia.
AB  - OBJECTIVES: To identify the prevalence and risk factors in the development of
      Neurogenic Heterotopic Ossification (NHO) in traumatic brain and spinal cord
      injured patients admitted to specialised units. METHODS: An audit protocol was
      used to gather all clinically relevant data, in specific patient groups, relating
      to the prevalence of NHO, and was statistically analysed to identify traumatic
      brain injury (TBI) and traumatic spinal cord injury (TSCI) patients at high risk
      of developing NHO. RESULTS: 262 TBI and 151 TSCI patients were identified. NHO
      was diagnosed in 10 and 16 patients with TBI and TSCI, respectively; 18
      clinically relevant characteristics were analysed for association with NHO in
      these patient groups. The only common variables associated with NHO in both
      neurological conditions were deep vein thrombosis and/or pulmonary emboli
      (DVT/PE). CONCLUSIONS: The prevalence of NHO in TBI patients is less than one
      third of that found in TSCI patients, ~4% and 11%, respectively. This study also
      suggests that the risk factors associated with NHO in TBI patients are distinct
      from those identified as risk factors in TSCI patients.

PMID- 24583538
TI  - The pQCT 'Bone Strength Indices' (BSIs, SSI). Relative mechanical impact and
      diagnostic value of the indicators of bone tissue and design quality employed in
      their calculation in healthy men and pre- and post-menopausal women.
AB  - The pQCT-assessed Bone Strength Indices (BSI's, SSI) depend on the product of a
      'quality' indicator, the cortical vBMD (vCtD), and a 'design' indicator, one of
      the cross-sectional moments of inertia or related variables (MIs) in long bones.
      As the MIs vary naturally much more than the vCtD and represent different
      properties, it could be that the variation of the indices might not reflect the
      relative mechanical impact of the variation of their determinant factors in
      different individuals or circumstances. To understand this problem, we determined
      the vCtD and MI's in tibia scans of 232 healthy men and pre- and post-MP women,
      expressed in SD of the means calculated for each group, and analyzed the
      independent influence of 1 SD unit of variation of each factor on that of the
      indices by multiple correlations. Results showed: 1. that the independent
      influence of the MIs on the indices was generally larger than that of the vCtD,
      and 2. that in post-MP women the influence of the vCtD was larger than it was in
      the other groups. This confirms the view that inter-individual variation of vCtD
      is comparatively small, and that mechanical competence of human bone is mostly
      determined by 'design' factors. 

PMID- 24583539
TI  - Association between insulin resistance, lean mass and muscle torque/force in
      proximal versus distal body parts in healthy young men.
AB  - OBJECTIVES: The purpose of this study was to investigate whether there is already
      an association of insulin resistance (IR) with muscle mass and -force/torque in
      an adult population and whether this relationship is the same in distal and
      proximal body parts. METHODS: 358 Healthy young men were divided into a more
      insulin sensitive (MIS) (n=89) and a less insulin sensitive (LIS) group (n=89),
      respectively using lower and upper quartiles of HOMA-IR index (Homeostasis Model
      Assessment of IR). Muscle force/torque and lean mass, were compared between the
      two groups. RESULTS: LIS subjects had higher absolute thigh lean mass, but not
      higher thigh muscle torque, resulting in a lower torque per kg muscle. In upper
      arm, lean mass was higher in LIS subjects, but also absolute muscle torque
      resulted higher. For handgrip force, the LIS and MIS group had similar results,
      despite a trend towards higher forearm lean mass in LIS subjects. Lean mass % of
      total lean mass is lower in LIS subjects in more distal body parts. CONCLUSIONS:
      Already in a young healthy population, IR seems to be associated with lower
      force/torque per muscle mass and lower lean mass % of total lean mass
      predominantly in more distal body parts.

PMID- 24583540
TI  - High force eccentric exercise enhances serum tartrate-resistant acid phosphatase
      5b and osteocalcin.
AB  - We investigated the effects of eccentric contractions (ECs) on bone metabolism
      markers and the relationship between bone metabolism and skeletal muscle related
      protein. Seventeen young untrained men were divided into two groups and performed
      either 60 or 30 maximal ECs. We measured serum levels of osteocalcin (OC), bone
      alkaline phosphatase, cross-linked N-telopeptide of type I collagen (NTx), and
      tartrate-resistant acid phosphatase 5b (TRACP-5b), growth hormone (GH), and
      insulin-like growth factor-1 (IGF-1). Blood samples were collected for up to five
      days after ECs. OC with 60 ECs were significantly higher than with 30 ECs (2
      hours; p<0.05, day 1 and day 5; p<0.01). TRACP-5b with 60 ECs were significantly
      higher than with 30 ECs (day 3 and day 5; p<0.001). IGF-1 and OC were
      significantly positively correlated with 60 ECs (2 hours, day 1, and day 5;
      p<0.05). There were also significant positive correlations between IGF-1 and NTx
      with 60 ECs (2 hours, p<0.01; day 1, p<0.05). We found that one bout of severe
      ECs caused increases in OC and TRACP-5b, which promote increased bone metabolism.
      Our results suggest that contraction-induced IGF-1 may activate OC and NTx in
      acute response. 

PMID- 24583541
TI  - Acute unilateral leg vibration exercise improves contralateral neuromuscular
      performance.
AB  - OBJECTIVES: To examine the post-exercise cross-transfer effects of acute whole
      body vibration (WBV). METHODS: Seventeen healthy male volunteers (20.8 +/- 1.2 y)
      performed three unilateral vibration conditions in a randomized order: 1) WBV-50
      Hz [high amplitude]; 2) WBV-30 Hz [low amplitude]; and 3) a control no WBV
      condition (Sham) applied to the dominant leg. Each condition involved maximal
      voluntary isometric contractions (MVC) followed by three leg press explosive
      repetitions (40% MVC) with non-dominant and dominant legs; which were conducted
      prior to and post vibration (immediately; 2 min and 5 min). Surface
      electromygraphy (sEMG) of the vastus lateralis (VL) and medial gastrocnemius (MG)
      were measured throughout each condition. RESULTS: A condition x leg x time
      interaction effect was detected (p=0.001) where 50 Hz-High in the stimulated leg
      enhanced mean velocity at post-2 min compared to 30 Hz-Low and Sham, remaining
      elevated at post-5 min. Similarly, 50 Hz-High in the non-stimulated leg increased
      mean velocity at post-immediately and post-2 min compared to 30 Hz-Low and Sham.
      There were no changes in sEMG of VL and GM in the stimulated and non-stimulated
      post-conditions. CONCLUSION: WBV (50 Hz) can augment cross-transfer in
      neuromuscular performance. WBV could provide an alternate method of unilateral
      training to promote cross education explosive strength.

PMID- 24583542
TI  - The creatine kinase response to resistance exercise.
AB  - Resistance exercise can result in localized damage to muscle tissue. This damage
      may be observed in sarcolemma, basal lamina, as well as, in the contractile
      elements and the cytoskeleton. Usually the damage is accompanied by release of
      enzymes such as creatine kinase (CK) and lactate dehydrogenase, myoglobin and
      other proteins into the blood. Serum CK has been proposed as one of the best
      indirect indicators of muscle damage due to its ease of identification and the
      relatively low cost of assays to quantify it. Thus, CK has been used as an
      indicator of the training intensity and a diagnostic marker of overtraining.
      However, some issues complicate CK's use in this manner. There is great
      interindividual variability in serum CK, which complicates the assignment of
      reliable reference values for athletes. Furthermore, factors such as training
      level, muscle groups involved, and gender can influence CK levels to a greater
      extent than differences in exercise volume completed. This review will detail the
      process by which resistance exercise induces a rise in circulating CK, illuminate
      the various factors that affect the CK response to resistance exercise, and
      discuss the relative usefulness of CK as a marker of training status, in light of
      these factors. 

PMID- 24583544
TI  - In vivo measurements of human bone deformation using optical segment tracking:
      surgical approach and validation in a three-point bending test.
AB  - The purpose of the study was to validate optical segment tracking, a new method
      for in vivo human tibia deformation measurements and to assess bending in a three
      point bending test. The approach relies upon optical motion capturing of
      reflecting marker clusters affixed to the bone via screws inserted three
      millimeters into the corticalis in local anesthesia. The method was tested in
      five healthy subjects. Screws were left in place for six to eight hours and a
      variety of exercises performed. A pain questionnaire was used to assess pain
      levels. PQCT-images were taken to locate screw holes in the bone. A three-point
      bending test was performed and repeatability evaluated. The new method shows good
      feasibility though this was previously considered impossible by many experts.
      Local anesthesia works for screw implantation and explantation. Results show
      linearity with an average of 0.25 degrees per 10 kg of weight applied with good
      repeatability (average variation coefficient 8%). Optical segment tracking is
      feasible for human in vivo bone deformation measurements. There is a variety of
      possible clinical and experimental applications including stability testing of
      osteosyntheses and joints, monitoring of bone healing, evaluation of exercises in
      physiotherapy, and assessment of bone deformation patterns in bone disease. 

PMID- 24583543
TI  - Bone loss from high repetitive high force loading is prevented by ibuprofen
      treatment.
AB  - We examined roles of loading and inflammation on forearm bones in a rat model of
      upper extremity overuse. Trabecular structure in distal radius and ulna was
      examined in three groups of young adult rats: 1) 5% food-restricted that
      underwent an initial training period of 10 min/day for 5 weeks to learn the
      repetitive task (TRHF); 2) rats that underwent the same training before
      performing a high repetition high force task, 2 hours/day for 12 weeks (HRHF);
      and 3) food-restricted only (FRC). Subsets were treated with oral ibuprofen
      (IBU). TRHF rats had increased trabecular bone volume and numbers, osteoblasts,
      and serum osteocalcin, indicative of bone adaptation. HRHF rats had constant
      muscle pulling forces, showed limited signs of bone adaptation, but many signs of
      bone resorption, including decreased trabecular bone volume and bone mineral
      density, increased osteoclasts and bone inflammatory cytokines, and reduced
      median nerve conduction velocity (15%). HRHF+IBU rats showed no trabecular
      resorptive changes, no increased osteoclasts or bone inflammatory cytokines, no
      nerve inflammation, preserved nerve conduction, and increased muscle voluntary
      pulling forces. Ibuprofen treatment preserved trabecular bone quality by reducing
      osteoclasts and bone inflammatory cytokines, and improving muscle pulling forces
      on bones as a result of reduced nerve inflammation. 

PMID- 24583545
TI  - Magnetic resonance imaging of bone and muscle traits at the hip: an in vivo
      precision study.
AB  - OBJECTIVE: To determine the in vivo precision of MRI-based measures of bone and
      muscle traits at the hip. METHODS: Left proximal femoral neck and shaft of 14
      participants (5M:9 F; age:21-68) were scanned 3 times using a 1.5 T MRI.
      Commercial and custom image processing methods were used to derive bone geometry
      and strength traits at the proximal femoral neck and shaft along with muscle area
      of various muscle groups at the shaft site. For precision, root mean square
      coefficients of variation (CV%rms) and standard deviations (SDrms) were
      calculated. RESULTS: At the femoral neck, CV%rms for area-based bone measures
      ranged between 1.7-5.0%; CV%rms for cortical thickness varied from 4.7 to 5.6%;
      and CV%rms for bending, torsional and buckling-based strength indices ranged
      between 4.6-7.1%. At the femoral shaft, CV%rms for bone area ranged between 1.2
      3.0%; CV%rms for cortical thickness varied from 1.7 to 2.0%; and CV%rms for
      bending and buckling-based strength indices ranged between 1.4-3.1%. For muscle
      area, CV%rms ranged between 1.3-4.5%. CONCLUSIONS: MRI-based measures of bone and
      muscle traits at the proximal femoral neck and shaft demonstrated in vivo
      precision errors <7.1%. MRI is a promising 3D technique for monitoring changes in
      bone and muscle at the clinically important hip.

PMID- 24583546
TI  - Study protocol, implementation, and verification of a short versatile upright
      exercise regime during 5 days of bed rest.
AB  - OBJECTIVES: This work provides a reference for future papers originating from
      this study by providing basic results on body mass, urine volume, and hemodynamic
      changes to 5 days of bed rest (BR) and by describing acute cardio
      respiratory/mechanographic responses to a short versatile upright exercise
      battery. METHODS: Ten male subjects (mean +/- SEM age: 29.4 +/- 1.5 years;
      height: 178.8 +/- 1.5 cm; body mass: 77.7 +/- 1.5 kg) performed, in random order,
      5 days of 6 degrees  head-down tilt (HDT) BR with no exercise (CON), or BR with
      daily 25 minutes of quiet upright standing (STA) or upright locomotion
      replacement training (LRT). RESULTS: Plasma volume, exercise capacity and
      orthostatic tolerance decreased similarly between interventions following 5 days
      of BR. Upright heart rate during LRT and STA increased throughout BR; from 137 +/
      4 bpm to 146 +/- 4 bpm for LRT (P<0.01); and from 90 +/- 3 bpm to 102 +/- 6 bpm
      (P<0.001) for STA. CONCLUSION: the overall similarity in the response to BR, and
      increase in upright heart rate during the LRT sessions suggest early and
      advancing cardiovascular deconditioning during 5 days of BR bed rest, which was
      not prevented by the versatile exercise regime.

PMID- 24583547
TI  - The effect of systemic administration of sclerostin antibody in a mouse model of
      distraction osteogenesis.
AB  - Distraction osteogenesis (DO) is a successful technique for bone lengthening, but
      one problem is the need to keep an external fixator in place until bone
      completely regenerates. We hypothesized that the systemic administration of
      sclerostin antibodies (Scl-Ab) can accelerate bone regeneration in a mouse model
      of DO. A total of 110 mice were randomized to receive one intravenous injection
      per week of either Scl-Ab (100 mg per kg body weight) or saline after DO surgery.
      Mice were sacrificed on day 11, 17, 34 or 51 post-surgery. Microcomputed
      tomography showed that bone volume per tissue volume of the Scl-Ab treated group
      was significantly higher on day 11 (P=0.009). Histological examinations indicated
      that chondrocytes and fibrocartilage predominated in the Scl-Ab group at day 11.
      The radiographic score of bone healing was also higher in Scl-Ab treated animals
      at day 11. There was a trend towards higher ultimate force and work to failure in
      Scl-Ab treated groups on day 34 and 51 (P>0.05). These data suggest the potential
      utility of Scl-Ab to reduce the time during DO when an external fixator is
      required. 

PMID- 24583548
TI  - Acute Achilles tendinopathy: effect of pain control on leg stiffness.
AB  - Tendinopathies are a major cause of disability in the athletic population; the
      main purpose of the treatment of these injuries is to reduce pain and improve
      function. The aim of this study was to evaluate the effect of NSAIDs on leg
      stiffness of patients suffering acute unilateral Achilles tendinopathy. Twenty
      eight eligible male athletes (aged 39.1 +/- 10.3 y) suffering acute Achilles
      tendinopathy were treated with etoricoxib (120 mg oral once daily) during 7 days.
      Pain (100-mm visual analogue scale-VAS), analgesic effect (percentage of 100-mm
      VAS reduction), and leg stiffness were evaluated pre- and post- anti-inflammatory
      treatment. Results of this study showed that over the 7-day treatment period,
      etoricoxib provided significant relief of Achilles tendon pain (VAS) compared to
      that experienced at baseline: 54.5 +/- 21.6 and 24.5 +/- 24.8, respectively
      (p<0.001). Leg stiffness showed a significant improvement after one-week NSAID
      therapy: LSR 0.89 +/- 0.1 vs. 0.97 +/- 0.1; (p=0.02). In conclusion, findings of
      this study demonstrated that patients suffering acute unilateral Achilles
      tendinopathy increased their leg stiffness of the affected side after oral anti
      inflammatory therapy. Effective control of tendon pain in the acute phase of such
      sports-related injuries may contribute to improve capabilities associated with
      high performance like leg stiffness.

PMID- 24583550
TI  - Buschke-Ollendorff syndrome accidentally diagnosed after a left ankle sprain.

PMID- 24583551
TI  - FOXM1 and androgen receptor co-regulate CDC6 gene transcription and DNA
      replication in prostate cancer cells.
AB  - CDC6 is a key component of the DNA replication initiation machinery, and its
      transcription is regulated by E2F or androgen receptor (AR) alone or in
      combination in prostate cancer (PCa) cells. Through both overexpression and
      knockdown approaches, we found that in addition to its effects on the E2F
      pathway, the cell proliferation specific transcription factor FOXM1 stimulated
      CDC6 transcription in cooperation with AR. We have identified a forkhead box
      motif in the CDC6 proximal promoter that is occupied by FOXM1 and is sufficient
      to drive FOXM1-regulated transcription. Indirectly, FOXM1 elevated AR protein
      levels and AR dependent transcription. Furthermore, FOXM1 and AR proteins
      physically interact. Using synchronized cultures, we observed that CDC6
      expression is elevated near S phase of the cell cycle, at a time coinciding with
      elevated FOXM1 and AR expression and CDC6 promoter occupancy by both AR and FOXM1
      proteins. Androgen increased the binding of AR protein to CDC6 promoter, and AR
      and FOXM1 knockdown decreased AR binding. These results provided new evidence for
      the regulatory mechanism of aberrant CDC6 oncogene transcription by FOXM1 and AR,
      two highly expressed transcription factors in PCa cells. Functionally, the
      cooperation of FOXM1 and AR accelerated DNA synthesis and cell proliferation by
      affecting CDC6 gene expression. Furthermore, siomycin A, a proteasome inhibitor
      known to inhibit FOXM1 expression and activity, inhibited PCa cell proliferation
      and its effect was additive to that of bicalutamide, an antiandrogen commonly
      used to treat PCa patients. 

PMID- 24583552
TI  - Readers of histone methylarginine marks.
AB  - Arginine methylation is a common posttranslational modification (PTM) that alters
      roughly 0.5% of all arginine residues in the cells. There are three types of
      arginine methylation: monomethylarginine (MMA), asymmetric dimethylarginine
      (ADMA), and symmetric dimethylarginine (SDMA). These three PTMs are enriched on
      RNA-binding proteins and on histones, and also impact signal transduction
      cascades. To date, over thirty arginine methylation sites have been cataloged on
      the different core histones. These modifications alter protein structure, impact
      interactions with DNA, and also generate docking sites for effector molecules.
      The primary "readers" of methylarginine marks are Tudor domain-containing
      proteins. The complete family of thirty-six Tudor domain-containing proteins has
      yet to be fully characterized, but at least ten bind methyllysine motifs and
      eight bind methylarginine motifs. In this review, we will highlight the
      biological roles of the Tudor domains that interact with arginine methylated
      motifs, and also address other types of interactions that are regulated by these
      particular PTMs. This article is part of a Special Issue entitled: Molecular
      mechanisms of histone modification function. 

PMID- 24583553
TI  - Themes and variations in riboswitch structure and function.
AB  - The complexity of gene expression control by non-coding RNA has been highlighted
      by the recent progress in the field of riboswitches. Discovered a decade ago,
      riboswitches represent a diverse group of non-coding mRNA regions that possess a
      unique ability to directly sense cellular metabolites and modulate gene
      expression through formation of alternative metabolite-free and metabolite-bound
      conformations. Such protein-free metabolite sensing domains utilize sophisticated
      three-dimensional folding of RNA molecules to discriminate between a cognate
      ligand from related compounds so that only the right ligand would trigger a
      genetic response. Given the variety of riboswitch ligands ranging from small
      cations to large coenzymes, riboswitches adopt a great diversity of structures.
      Although many riboswitches share structural principles to build metabolite
      competent folds, form precise ligand-binding pockets, and communicate a ligand
      binding event to downstream regulatory regions, virtually all riboswitch classes
      possess unique features for ligand recognition, even those tuned to recognize the
      same metabolites. Here we present an overview of the biochemical and structural
      research on riboswitches with a major focus on common principles and individual
      characteristics adopted by these regulatory RNA elements during evolution to
      specifically target small molecules and exert genetic responses. This article is
      part of a Special Issue entitled: Riboswitches.

PMID- 24583554
TI  - Computational analysis of riboswitch-based regulation.
AB  - Advances in computational analysis of riboswitches in the last decade have
      contributed greatly to our understanding of riboswitch regulatory roles and
      mechanisms. Riboswitches were originally discovered as part of the sequence
      analysis of the 5'-untranslated region of mRNAs in the hope of finding novel gene
      regulatory sites, and the existence of structural RNAs appeared to be a spurious
      phenomenon. As more riboswitches were discovered, they illustrated the diversity
      and adaptability of these RNA regulatory sequences. The fact that a chemically
      monotonous molecule like RNA can discern a wide range of substrates and exert a
      variety of regulatory mechanisms was subsequently demonstrated in diverse genomes
      and has hastened the development of sophisticated algorithms for their analysis
      and prediction. In this review, we focus on some of the computational tools for
      riboswitch detection and secondary structure prediction. The study of this simple
      yet efficient form of gene regulation promises to provide a more complete picture
      of a world that RNA once dominated and allows rational design of artificial
      riboswitches. This article is part of a Special Issue entitled: Riboswitches.

PMID- 24583556
TI  - Comparative study of the immunogenicity in mice and monkeys of an inactivated
      CA16 vaccine made from a human diploid cell line.
AB  - The coxsackie A16 virus (CA16), along with enterovirus 71 (EV71), is a primary
      pathogen that causes hand, foot, and mouth disease (HFMD). To control HFMD, CA16,
      and EV71 vaccines are needed. In this study, an experimental inactivated CA16
      vaccine was prepared using human diploid cells, and the vaccine's immunogenicity
      was analyzed in mice and rhesus monkeys. The results showed that the neutralizing
      antibody was developed in a dose-dependent manner, and was sustained for 70 days
      with an average GMT (geometric mean titer) level of 80 to 90 in immunized mouse
      and for 56 days with GMT of higher than 300 in monkeys. The neutralizing antibody
      had a cross-neutralizing activity against different viral strains (genotype A and
      B), and the specific IFN-gamma-secreting cell response was activated by these
      virus strains in an ELISPOT assay. This study provides evidence for the potential
      use of inactivated CA16 as a candidate for use in vaccines. 

PMID- 24583558
TI  - [A simple algorithm for anemia].
AB  - The author presents a novel algorithm for anaemia based on the erythrocyte
      haemoglobin content. The scheme is based on the aberrations of erythropoiesis and
      not on the pathophysiology of anaemia. The hemoglobin content of one erytrocyte
      is between 28-35 picogram. Any disturbance in hemoglobin synthesis can lead to a
      lower than 28 picogram hemoglobin content of the erythrocyte which will lead to
      hypochromic anaemia. In contrary, disturbances of nucleic acid metabolism will
      result in a hemoglobin content greater than 36 picogram, and this will result in
      hyperchromic anaemia. Normochromic anemia, characterised by hemoglobin content of
      erythrocytes between 28 and 35 picogram, is the result of alteration in the
      proliferation of erythropoeisis. Based on these three categories of anaemia, a
      unique system can be constructed, which can be used as a model for basic
      laboratory investigations and work-up of anaemic patients.

PMID- 24583555
TI  - Chromatin dynamics: interplay between remodeling enzymes and histone
      modifications.
AB  - Chromatin dynamics play an essential role in regulating the accessibility of
      genomic DNA for a variety of nuclear processes, including gene transcription and
      DNA repair. The posttranslational modification of the core histones and the
      action of ATP-dependent chromatin remodeling enzymes represent two primary
      mechanisms by which chromatin dynamics are controlled and linked to nuclear
      events. Although there are examples in which a histone modification or a
      remodeling enzyme may be sufficient to drive a chromatin transition, these
      mechanisms typically work in concert to integrate regulatory inputs, leading to a
      coordinated alteration in chromatin structure and function. Indeed, site-specific
      histone modifications can facilitate the recruitment of chromatin remodeling
      enzymes to particular genomic regions, or they can regulate the efficiency or the
      outcome of a chromatin remodeling reaction. Conversely, chromatin remodeling
      enzymes can also influence, and sometimes directly modulate, the modification
      state of histones. These functional interactions are generally complex,
      frequently transient, and often require the association of myriad additional
      factors. This article is part of a Special Issue entitled: Molecular mechanisms
      of histone modification function. 

PMID- 24583557
TI  - [Pathomechanism and clinical impact of myelofibrosis in neoplastic diseases of
      the bone marrow].
AB  - Polyclonal mesenchymal cells (fibroblasts, endothelial cells, pericytes,
      osteoblasts, reticular cells, adipocytes, etc.) of the bone marrow create a
      functional microenvironment, which actively contributes to the maintenance of
      hemopoesis. This takes place through cellular interactions via growth factors,
      cytokines, adhesion molecules and extracellular matrix components, as well as
      through the control of calcium and oxygen concentration. Inflammatory and
      neoplastic diseases of the bone marrow result in pathologic interaction between
      hemopoietic progenitors and stromal cells. This may lead to the activation and
      expansion of the stroma and to the accumulation of reticulin and collagen fibers
      produced by mesenchymal cells. Clinically relevant fiber accumulation, termed as
      myelofibrosis accompanies many diseases, although, the extent and the consequence
      of myelofibrosis are variable in different disorders. The aim of this review is
      to summarize basic features of the normal bone marrow mesenchymal environment and
      the pathological process leading to myelofibrosis. In addition, the special
      features of myelofibrosis in bone marrow diseases, including myeloproliferative
      neoplasia, myelodysplastic syndrome and other neoplastic conditions are
      discussed.

PMID- 24583559
TI  - [Preliminary experiences with low-dose computed tomography for lung cancer
      screening in Hungary].
AB  - INTRODUCTION: Lung cancer has the highest mortality rate of all types of cancers
      both in developed countries and Hungary. AIM: To obtain experience and facilitate
      the application of low-dose computed tomography-based lung cancer screening as a
      targeted public health screening procedure. METHOD: Volunteers without thoracic
      complaints above the age of 40 years (n = 963) were screened for lung cancer
      using digital chest radiography and low-dose computed tomography. RESULTS: Two
      lung cancers were found among the participants screened with digital chest
      radiography (0.2%). After informed consent, 173 individuals with normal chest
      radiography findings (n = 943) took the opportunity to voluntarily participate in
      low-dose computed tomography screening for lung cancer. After 3 or 12 months, 65
      individuals had follow up control examinations based on the size and
      characteristics of the detected lesions. Among them, one participant was found to
      have lung cancer using low-dose computed tomography. CONCLUSIONS: These results
      indicate that low-dose computed tomography-based lung cancer screening as a
      public health screening procedure can enhance the success of screening with 50%
      (from 0.2% to 0.3%). The cost-benefit ratio can be raised if chest radiography is
      performed prior to the low-dose computed tomography examination.

PMID- 24583560
TI  - [Flow cytometry in the diagnosis of hemophagocytic lymphohistiocytosis in a case
      with fatal outcome].
AB  - Hemophagocytic lymphohistiocytosis is a multisystem inflammation, generated by
      the uncontrolled and excessive activation of cytotoxic T lymphocytes and natural
      killer cells. Severe immunodeficiency and generalized macrophage activation can
      often be detected in the background of this life threatening disorder. It is
      classified as a primary immunodeficiency. Functional abnormalities of the
      perforin protein or defects in granule secretory mechanisms are caused by gene
      mutations in most cases. Diagnostic criteria of hemophagocytic
      lymphohistiocytosis are the following: fever, splenomegaly, cytopenias affecting
      at least two of the 3 lineages in peripheral blood, hypertriglyceridemia and
      hyperferritinemia, elevated serum level of soluble interleukin-2 receptor
      (sCD25), hypofibrinogenemia, hemophagocytosis in bone marrow and decreased
      cytotoxic T cell and natural killer cell activity. In this case report the
      authors summarize the utility of functional flow cytometry in the diagnosis of
      hemophagocytic lymphohistiocytosis. Using flow cytometry, elevated intracellular
      perforin content, decreased killing activity of cytotoxic T cells and natural
      killer cells, and impaired cell surface expression of CD107a (LAMP1 protein) from
      in vitro stimulated blood lymphocytes were detected. Abnormal secretion of
      perforin was also demonstrated. Genetic testing revealed mutation of the MUNC 13
      4 gene, which confirmed the base of the abnormal flow cytometric findings. This
      case report demonstrates the value of functional flow cytometry in the rapid
      diagnosis of genetically determined hemophagocytic lymphohistiocytosis, a
      condition in which early diagnosis is critical for optimal management. The
      authors emphasize the significance of functional flow cytometry in the
      differential diagnosis of immunodeficiencies.

PMID- 24583561
TI  - [Gabor Petri, the great reformer of Hungarian surgery was born 100 years ago].

PMID- 24583563
TI  - Therapeutic experiences of community gardens: putting flow in its place.
AB  - This paper develops the concept of therapeutic place experiences by considering
      the role of activity. Research of community gardening finds that particular tasks
      are therapeutic and exhibit the characteristics of flow, but those who lack
      influence over their community gardening are less likely to benefit from flow as
      their sense of control is reduced. The notion of emplaced flow is proposed to
      locate individual experiences amongst socio-spatial factors which limit self
      determinacy and therefore affect wellbeing. Emplacing flow prompts critical
      reflection on who is excluded from therapeutic place experiences, and whether
      sites offering momentary escape have an enduring impact on wellbeing. 

PMID- 24583564
TI  - Candidemia: incidence rates, type of species, and risk factors at a tertiary care
      academic hospital in China.
AB  - OBJECTIVES: To investigate the incidence rates of candidemia in hospitalized
      patients and to identify differences in risk factors of patients with Candida
      albicans and non-C. albicans and with Candida guilliermondii and non-C.
      guilliermondii candidemia. METHODS: Non-immunosuppressed, non-neutropenic
      inpatients with candidemia diagnosed after admission were included in this
      retrospective observational study at a tertiary academic hospital in China.
      RESULTS: During the study period (January 2009 to December 2011), 238 eligible
      patients had candidemia episodes with an incidence rate 5.4%. Of these patients,
      29.8% had candidemia due to C. albicans, 27.7% due to C. parapsilosis, and 16.4%
      due to C. guilliermondii. Diabetes was a significant risk factor for patients
      with candidemia due to C. albicans (35.2%, 25/71) compared to candidemia due to
      non-C. albicans spp (13.2%, 22/167) (odds ratio (OR) 0.2792, 95% confidence
      interval (CI) 0.144-0.5412; p < 0.001). Compared to patients with candidemia due
      to non-C. guilliermondii spp, preterm birth with low birth weight (OR 0.0887, 95%
      CI 0.0398-0.1977; p < 0.001), intravenous nutrition (OR 0.0662, 95% CI 0.0226
      0.1938), and surgery (OR 0.0662, 95% CI 0.0226-0.1938; p < 0.001) were
      significant risk factors for candidemia due to C. guilliermondii. Furthermore,
      compared to patients with candidemia due to C. albicans, patients with candidemia
      due to C. guilliermondii had markedly higher rates of central venous
      catheterization (85.9%, 61/71 vs. C. guilliermondii: 100%, 39/39; p = 0.013) and
      intravenous nutrition (89.7%, 35/39 vs. C. albicans: 42.2%, 30/71; p < 0.001).
      CONCLUSIONS: Candidemia due to C. albicans ranks first in incidence, and
      candidemia due to C. guilliermondii occurs in a significant proportion of our
      hospitalized patients.

PMID- 24583565
TI  - Reduction in the incidence of hospital-acquired Clostridium difficile infection
      through infection control interventions other than the restriction of
      antimicrobial use.
AB  - A combination of infection control interventions, consisting of education,
      isolation, hand hygiene, contact precautions, and environmental disinfection, was
      implemented in the medical intensive care unit (MICU). The strict restriction of
      the use of antimicrobial agents was not included in this study. Following the
      interventions, the incidence of Clostridium difficile infection (CDI) in the MICU
      decreased significantly, by 67%, from 4.70 to 1.53 cases/1000 patient days (p =
      0.012), while the hospital-wide incidence of CDI increased significantly from
      0.93 to 1.17 cases/1000 patient-days (p = 0.021). A multifaceted approach to
      minimize C. difficile exposure can be effective in reducing the incidence of
      hospital-acquired CDI under conditions that do not allow for a restriction in the
      use of antimicrobial agents. 

PMID- 24583566
TI  - A prospective, open-label study to evaluate symptomatic remission in
      schizophrenia with risperidone long-acting injectable in Korea.
AB  - This study was designed to investigate long-term clinical outcomes of risperidone
      long-acting injectable (RLAI) in patients with schizophrenia or schizoaffective
      disorder. An open-label, 48-week, prospective study of RLAI treatment was carried
      out at 63 centers in South Korea. Initial and maintenance dosage of RLAI were
      adjusted according to clinical judgment. Efficacy was measured by the remission
      rate, continuation rate, and changes in the clinical measurements such as eight
      items of the Positive and Negative Symptom Scale (PANSS), the Clinical Global
      Impression - Severity, and the Schizophrenia Quality of Life Scale. In terms of
      the safety, Simpson-Angus rating Scale, adverse events (AEs), and BMI were
      investigated. Of the 522 patients who were enrolled, 472 patients who had been
      assessed on the eight items of PANSS at baseline and at least once during RLAI
      treatment were included in the intention-to-treat (ITT) population. The per
      protocol (PP) population included 184 patients (39.0%), who completed all
      assessments during 48 weeks of the follow-up period. Total scores of eight items
      of PANSS, Clinical Global Impression - Severity, and Schizophrenia Quality of
      Life Scale were reduced significantly from baseline to endpoint in both ITT and
      PP populations. The mean dose (SD) of RLAI was 33.2 (7.6) mg. In the PP
      population, the number of patients who scored 1-3 on eight items of PANSS were 47
      (25.5%) at baseline and 144 (78.3%) at 48 weeks. According to the remission
      defining as scores 1-3 on eight items of PANSS sustaining of at least 6 months'
      duration by Andreasen, the numbers of patients who achieved remission were 45
      (24.5%) at 24 weeks and 120 (65.2%) at 48 weeks. A significant decrease in the
      mean score of Simpson-Angus rating Scale and a significant increase in BMI over
      time in last observation carried forward were observed, and patients who
      fulfilled the remission criteria during the study showed more weight gain than
      those who did not. During the study period, a total of 645 AEs were noted in 233
      patients (49.3%) who were included in the ITT population. Sixty-nine serious AEs
      in 51 patients were reported, but all of them were not directly attributable to
      administration of RLAI. This prospective, open-label study showed improvements in
      symptom and AEs and a significant increase in BMI during 48 weeks of biweekly
      RLAI treatment. The rate of study completion was 39.0% and the remission rate
      among those who completed the study was 65.2%. None of the serious AEs were
      directly related to the administration of RLAI. 

PMID- 24583567
TI  - Predictors of functional improvement in employed adults with major depressive
      disorder treated with desvenlafaxine.
AB  - We carried out a secondary analysis of a double-blind, placebo-controlled trial
      of desvenlafaxine for major depressive disorder (MDD) to explore the associations
      between depressive symptoms and subtypes, and functional outcomes, including work
      functioning. Employed outpatients with MDD were assigned randomly in a 2 : 1
      ratio to receive desvenlafaxine 50 mg/day or placebo for 12 weeks. Analyses were
      carried out post-hoc with the intent-to-treat (ITT) sample (N=427) and a
      prospectively defined modified ITT sample (N=310), composed of patients with
      baseline 17-item Hamilton Rating Scale for Depression score of at least 20.
      Functional outcomes at week 12 included items and factors from the Montgomery
      Asberg Depression Rating Scale, Sheehan Disability Scale, and the Work
      Productivity and Activity Impairment questionnaire. In the modified ITT sample,
      but not in the ITT sample, desvenlafaxine-treated patients showed significantly
      greater improvement in several functional outcomes in the responder, nonanxious,
      and normal-energy patient subgroups. Improvement in the 17-item Hamilton Rating
      Scale for Depression total score at week 2 predicted change at week 12 in several
      functional outcomes. Functional improvement at 12 weeks was greater in subgroups
      of patients and was also significantly predicted by early improvement in
      depressive symptoms in employed patients with MDD treated with desvenlafaxine. 

PMID- 24583568
TI  - Sites of institutional racism in public health policy making in New Zealand.
AB  - Although New Zealanders have historically prided ourselves on being a country
      where everyone has a 'fair go', the systemic and longstanding existence of health
      inequities between Maori and non-Maori suggests something isn't working. This
      paper informed by critical race theory, asks the reader to consider the counter
      narrative viewpoints of Maori health leaders; that suggest institutional racism
      has permeated public health policy making in New Zealand and is a contributor to
      health inequities alongside colonisation and uneven access to the determinants of
      health. Using a mixed methods approach and critical anti-racism scholarship this
      paper identifies five specific sites of institutional racism. These sites are:
      majoritarian decision making, the misuse of evidence, deficiencies in both
      cultural competencies and consultation processes and the impact of Crown filters.
      These findings suggest the failure of quality assurance systems, existing anti
      racism initiatives and health sector leadership to detect and eliminate racism.
      The author calls for institutional racism to be urgently addressed within New
      Zealand and this paper serves as a reminder to policy makers operating within
      other colonial contexts to be vigilant for such racism. 

PMID- 24583569
TI  - Victory for volunteerism? Scottish health board elections and participation in
      the welfare state.
AB  - This paper presents findings from a multimethod study of pilot elections held to
      choose members of health boards in the National Health Service in Scotland. We
      begin by proposing that much current public involvement practice is dominated by
      a volunteerist model, in which members of the public with time and skills to
      offer play essentially supportive and non-challenging roles within health care
      organizations. This model contrasts sharply with the adversarial, political model
      of electoral democracy. Nonetheless, drawing on a postal survey of voters, non
      participant observation of Boards, and semi-structured interviews with
      candidates, elected Board members and other stakeholders, we demonstrate that the
      introduction of elections did not overcome the volunteerist slant of current
      public involvement with health care organizations. Far from offering a 'quick
      fix' for policymakers seeking to ensure accountability of health care
      organizations, elections may produce remarkably similar outcomes to existing
      mechanisms of public involvement. 

PMID- 24583570
TI  - Bacteriophages infecting Bacteroides as a marker for microbial source tracking.
AB  - Bacteriophages infecting certain strains of Bacteroides are amid the numerous
      procedures proposed for tracking the source of faecal pollution. These
      bacteriophages fulfil reasonably well most of the requirements identified as
      appropriate for a suitable marker of faecal sources. Thus, different host strains
      are available that detect bacteriophages preferably in water contaminated with
      faecal wastes corresponding to different animal species. For phages found
      preferably in human faecal wastes, which are the ones that have been more
      extensively studied, the amounts of phages found in waters contaminated with
      human fecal samples is reasonably high; these amounts are invariable through the
      time; their resistance to natural and anthropogenic stressors is comparable to
      that of other relatively resistant indicator of faecal pollution such us
      coliphages; the abundance ratios of somatic coliphages and bacteriophages
      infecting Bacteroides thetaiotaomicron GA17 are unvarying in recent and aged
      contamination; and standardised detection methods exist. These methods are easy,
      cost effective and provide data susceptible of numerical analysis. In contrast,
      there are some uncertainties regarding their geographical stability, and
      consequently suitable hosts need to be isolated for different geographical areas.
      However, a feasible method has been described to isolate suitable hosts in a
      given geographical area. In summary, phages infecting Bacteroides are a marker of
      faecal sources that in our opinion merits being included in the "toolbox" for
      microbial source tracking. However, further research is still needed in order to
      make clear some uncertainties regarding some of their characteristics and
      behaviour, to compare their suitability to the one of emerging methods such us
      targeting Bacteroidetes by qPCR assays; or settling molecular methods for their
      determination. 

PMID- 24583571
TI  - Hypertonic saline as a therapy for pediatric concussive pain: a randomized
      controlled trial of symptom treatment in the emergency department.
AB  - OBJECTIVE: Three-percent hypertonic saline (HTS) is a hyperosmotic therapy used
      in pediatric traumatic brain injury to treat increased intracranial pressure and
      cerebral edema. It also promotes plasma volume expansion and cerebral perfusion
      pressure, immunomodulation, and anti-inflammatory response. We hypothesized that
      HTS will improve concussive symptoms of mild traumatic brain injury. METHODS: The
      study was a prospective, double-blind, randomized controlled trial. Children, 4
      to 7 years of age with a Glasgow Coma Scale score greater than 13, were enrolled
      from a pediatric emergency department following closed-head injury upon meeting
      Acute Concussion Evaluation criteria with head pain. Patients were randomized to
      receive 10 mL/kg of HTS or normal saline (NS) over 1 hour. Self-reported pain
      values were obtained using the Wong-Baker FACES Pain Rating Scale initially,
      immediately following fluids, and at 2 to 3 days of discharge. The primary
      outcome measure was change in self-reported pain following fluid administration.
      Secondary outcome measures were a change in pain and postconcussive symptoms
      within 2 to 3 days of fluid administration. We used an intention-to-treat
      analysis. RESULTS: Forty-four patients, ranging from 7 to 16 years of age with
      comparable characteristics, were enrolled in the study; 23 patients (52%)
      received HTS, and 21 (48%) received NS. There was a significant difference (P <
      0.001) identified in the self-reported improvement of pain following fluid
      administration between the HTS group (mean improvement = 3.5) and the NS group
      (mean improvement = 1.1). There was a significant difference (P = 0.01)
      identified in the self-reported improvement of pain at 2 to 3 days after
      treatment between the HTS group (mean improvement = 4.6) and the NS group (mean
      improvement = 3.0). We were unable to determine a difference in other
      postconcussive symptoms following discharge. CONCLUSIONS: Three-percent HTS is
      more effective than NS in acutely reducing concussion pain in children.

PMID- 24583572
TI  - Legislation in Quebec for all-terrain vehicles: are we doing enough?
AB  - OBJECTIVES: All-terrain vehicle (ATV) legislation in Quebec is among the most
      restrictive in Canada. The purpose of our study was to characterize the pediatric
      ATV traumas in our center and determine the impact of legislation. METHODS:
      Retrospective chart review of all patients seen in the emergency department after
      an ATV injury was done from 2005 to 2011. RESULTS: Seventy-tree patients (50 boys
      and 23 girls) with a mean age of 11 years (range, 3-17 years) were identified.
      Forty-nine percent were drivers, 40% were passengers, and 11% unknown. Forty-five
      percent did not reach the legal age of 16 years. Helmet use was documented in
      36%. Eighty-five percent were admitted to the floor, and 15% were discharged from
      the emergency department. Intensive care unit stay was necessary in 21%, and 60%
      were operated on. Most of the surgeries were for orthopedic, either extremities,
      spine, or pelvic (80%). The most frequent types of trauma were extremities (30%),
      head (30%), and face (25%). Head trauma was severe in 23%. Hospitalization rates
      for ATV injuries have remained unchanged in the last years. CONCLUSIONS: Despite
      implementation of ATV legislation regarding helmet use and minimal legal age, a
      lot of our patients did not obey these rules. This study demonstrates that strong
      legislation did not have a real impact on ATV morbidity in children. It is
      essential to develop strategies to enforce ATV users to respect legislation.

PMID- 24583573
TI  - Seasonal variation of presentation for headache in a pediatric emergency
      department.
AB  - OBJECTIVES: Headache is a common pediatric complaint. Our experience indicated
      that there was a seasonal variation in children seeking emergency department (ED)
      care for headache. We hypothesized that visits to the ED would be more common
      during the school year compared with that during the summer months. METHODS:
      Electronic medical record data were reviewed from January 1, 2008 through June
      30, 2010. All patients age 4 years and older with a chief complaint of headache
      were examined. Patients with ventriculoperitoneal shunts, intracranial mass,
      trauma, or stroke were excluded. The following data were accumulated: date of
      visit, birth date, sex, race, and diagnosis. Visits were grouped by month of
      occurrence and school year (September through May) and non-school year (June
      through August). Cumulative binomial probabilities were used to determine the
      likelihood of experiencing the observed number of occurrences or fewer in each
      period. RESULTS: A total of 2731 visits met the inclusion and exclusion criteria.
      Girls were older, more likely to be white, and more likely to be diagnosed with
      migraine. There is a clear nadir in May and June and a peak in September,
      October, and November that is statistically significant (P< 0.001) across age
      groups, sex, race, and headache type. These findings persisted when comparing the
      groups based on school year versus non-school year. CONCLUSIONS: Visits to the ED
      for headache were less common in May and June and more common during the fall.
      This remained true across headache type, age, sex, and racial groups.

PMID- 24583574
TI  - Development of a survey of teamwork and task load among medical providers: a
      measure of provider perceptions of teamwork when caring for critical pediatric
      patients.
AB  - INTRODUCTION: Teamwork training focuses on improving patient outcomes through
      better communication. Scales exist to assess providers' perceptions of teamwork;
      however, they are not designed for use immediately after the care of critically
      ill patients. OBJECTIVES: This study aimed to develop a survey to quantify
      providers' perceptions of teamwork and task load during critical care
      resuscitations in a PED and to use the tool to compare physician and nonphysician
      ratings of resuscitations. METHODS: Survey items were adapted from validated
      tools. The resulting survey contained 15 Likert scale items completed by
      providers immediately after resuscitations. An exploratory factor analysis was
      conducted. Mixed models, accounting for clustering of providers within
      resuscitations, tested for systematic differences in responses between physicians
      and nonphysicians and explored how well the factor scores predicted the overall
      "smoothness" of the resuscitation. RESULTS: Six hundred fifty-four surveys from
      169 resuscitations were conducted. The exploratory factor analysis identified 2
      factors with 13 items explaining 47% of the overall variance of "teamwork and
      communication" (Cronbach alpha = 0.80) and "task load" (Cronbach alpha = 0.77).
      There were no differences in factors predicting smoothness between physicians and
      nonphysicians (P = 0.27). Both were significant positive predictors of the
      outcome "the resuscitation went smoothly." CONCLUSIONS: The Survey of Teamwork
      and Task Load among Medical Providers was developed to evaluate providers'
      perceptions of teamwork immediately after care of critically ill patients in a
      pediatric emergency department. Items reflect 2 constructs, with good internal
      consistency. Responses did not vary by professional training, suggesting that it
      is useful for all providers. Both factors predicted the overall smoothness. Each
      was useful in predicting the perception that the resuscitation went smoothly.

PMID- 24583575
TI  - Diagnostic findings in infants presenting to a pediatric emergency department for
      lethargy or feeding complaints.
AB  - OBJECTIVES: Lethargy is a common complaint among infants in the pediatric
      emergency department (ED), yet there is little data to guide appropriate
      evaluation. The objectives of the study were (1) to determine the frequency of
      diagnoses requiring intervention/monitoring and (2) to identify predictors of
      these diagnoses. METHODS: A retrospective chart review of patients aged 0 to 6
      months with a chief complaint of lethargy or poor feeding from January 2004 to
      December 2009 was performed. Patients were excluded if they had a fever,
      hypothermia, a chronic medical condition, or a history of trauma. Charts were
      reviewed by a single investigator; 10% were reviewed by a second investigator for
      agreement. History, examination, laboratory and radiology results, ED and
      inpatient diagnoses, as well as return visits within 7 days were recorded.
      Frequencies of diagnoses and interventions were described, and history and
      examination findings associated with these categories were determined. RESULTS:
      Two hundred seventy-two patients were included; 34 patients (12.5%; 95%
      confidence interval [CI], 8.8%-17%) required intervention/monitoring. These
      patients were classified into 6 categories. Eighteen had hematologic disorders
      (6.6%; 95% CI, 4.0%-10.3%), 8 had dehydration (2.9%; 95% CI, 1.3%-5.7%), 2 had
      intracranial bleeds (0.7%; 95% CI, 0.09%-2.6%), 3 had serious bacterial
      infections (1%; 95% CI, 0.2%-3.2%), 1 had a cardiac disorder (0.4%; 95% CI,
      0.009%-2%), and 2 had neurologic disorders (0.7%; 95% CI, 0.9%-2.6%). Of the
      patients, 76% had conditions that were clinically evident (dehydration and
      hyperbilirubinemia requiring phototherapy). The patients with cardiac disorders,
      neurologic disorders, and intracranial bleeds all had abnormal examination
      findings in the ED. The 3 patients with serious bacterial infections were younger
      than 2 months of age and ill appearing; all had urinary tract infections.
      CONCLUSIONS: Infants with lethargy or poor feeding who require an intervention
      are likely to have conditions that are clinically evident or focal examination
      findings that lead to the diagnosis. Well-appearing infants with normal findings
      in examinations are unlikely to have a condition requiring intervention and
      should receive minimal testing.

PMID- 24583576
TI  - Validation of the accuracy of a transport ventilator utilizing a pediatric animal
      model.
AB  - OBJECTIVE: The objective of this study was to evaluate 2 transport ventilators
      utilizing both a test lung and a pediatric animal model. METHODS: Two transport
      ventilators were utilized for evaluations. A test lung or intubated, sedated pigs
      (n = 9) with healthy and injured lungs were ventilated using control and support
      modes. A test lung was used to evaluate alarm responsiveness, FIO2 accuracy,
      oxygen consumption, and duration of battery power. Pigs were utilized to evaluate
      the exhalation valve, ventilator response, volume accuracy, and noninvasive
      functionality. Respiratory mechanics were determined using a forced oscillation
      technique, and airway flow and pressure waveforms were acquired utilizing a
      pneumotachograph. RESULTS: For both ventilators, FIO2 accuracy was within 10%
      error. On an E cylinder of oxygen, the EMV+ operated for 3 hours 48 minutes and
      the LTV 1200 for 1 hour 4 minutes. On battery power, the LTV 1200 ventilated for
      6 hours 51 minutes and the EMV+ for 12 hours 8 minutes. Ventilator response time
      was less (36%), and delta pressure was greater (38%) for the EMV+ utilizing
      noninvasive ventilation. The percent error for displayed volume was less than 10%
      for the EMV+. CONCLUSIONS: In this study, we demonstrate that there are
      differences between the 2 ventilators in regard to oxygen consumption, duration
      of battery power, and volume accuracy. Clinicians should be aware of these
      differences to optimize the choice and use of both ventilators depending on
      clinical need/setting.

PMID- 24583577
TI  - Presentation to either the pediatric emergency department or primary care clinic
      for acute illness: the caregivers' perspective.
AB  - OBJECTIVES: This study aimed to understand and compare caregivers' perceptions of
      and attitudes toward care received in a primary care clinic (PCC) versus that
      received in the pediatric emergency department (PED) as well as the reasons for
      selecting either location to receive care for their child. METHODS: Surveys were
      administered to caregivers of children who receive their primary care at the same
      location who presented for a nonurgent sick visit to either the PCC or PED during
      regular PCC hours. RESULTS: One hundred fifty-one caregivers in the PCC and 83 in
      the PED completed the survey. Compared with caregivers who brought their child to
      the PED, those who presented to the PCC were more likely to report that the child
      had been sick for more than 2 days (P < 0.001), indicate that the child could
      wait more than 3 hours to be seen (P < 0.001), have called the PCC for advice
      (odds ratio [OR], 5.2; 95% confidence interval [CI], 2.9-9.2), have spoken with a
      nurse (OR, 3.7; 95% CI, 2.0-6.7), be satisfied with their phone call to the PCC
      (OR, 12.2; 95% CI, 6.4-23.1), and report that they could easily get in touch with
      the PCC (OR, 3.6; 95% CI, 1.8-7.3). Most caregivers who went to the PCC felt that
      it was more convenient (98.6%) and they would be seen more quickly (95.8%).
      CONCLUSIONS: Although all children had the same medical home, caregivers who
      presented to the PCC were more likely to have called the clinic, spoken with a
      nurse, and reported greater satisfaction with the PCC than those who brought
      their child to the PED.

PMID- 24583579
TI  - Communicating science in public controversies: Strategic considerations of the
      German climate scientists.
AB  - In public controversies on scientific issues, scientists likely consider the
      effects of their findings on journalists and on the public debate. A
      representative survey of 123 German climate scientists (42%) finds that although
      most climate scientists think that uncertainties about climate change should be
      made clearer in public they do not actively communicate this to journalists.
      Moreover, the climate scientists fear that their results could be misinterpreted
      in public or exploited by interest groups. Asking scientists about their
      readiness to publish one of two versions of a fictitious research finding shows
      that their concerns weigh heavier when a result implies that climate change will
      proceed slowly than when it implies that climate change will proceed fast. 

PMID- 24583580
TI  - The effect of mutation and selection on codon adaptation in Escherichia coli
      bacteriophage.
AB  - Studying phage codon adaptation is important not only for understanding the
      process of translation elongation, but also for reengineering phages for medical
      and industrial purposes. To evaluate the effect of mutation and selection on
      phage codon usage, we developed an index to measure selection imposed by host
      translation machinery, based on the difference in codon usage between all host
      genes and highly expressed host genes. We developed linear and nonlinear models
      to estimate the C->T mutation bias in different phage lineages and to evaluate
      the relative effect of mutation and host selection on phage codon usage. C->T
      biased mutations occur more frequently in single-stranded DNA (ssDNA) phages than
      in double-stranded DNA (dsDNA) phages and affect not only synonymous codon usage,
      but also nonsynonymous substitutions at second codon positions, especially in
      ssDNA phages. The host translation machinery affects codon adaptation in both
      dsDNA and ssDNA phages, with a stronger effect on dsDNA phages than on ssDNA
      phages. Strand asymmetry with the associated local variation in mutation bias can
      significantly interfere with codon adaptation in both dsDNA and ssDNA phages. 

PMID- 24583581
TI  - Nascent DNA synthesis during homologous recombination is synergistically promoted
      by the rad51 recombinase and DNA homology.
AB  - In this study, we exploited a plasmid-based assay that detects the new DNA
      synthesis (3' extension) that accompanies Rad51-mediated homology searching and
      strand invasion steps of homologous recombination to investigate the interplay
      between Rad51 concentration and homology length. Mouse hybridoma cells that
      express endogenous levels of Rad51 display an approximate linear increase in the
      frequency of 3' extension for homology lengths of 500 bp to 2 kb. At values below
      ~500 bp, the frequency of 3' extension declines markedly, suggesting that this
      might represent the minimal efficient processing segment for 3' extension.
      Overexpression of wild-type Rad51 stimulated the frequency of 3' extension by ~3
      fold for homology lengths <900 bp, but when homology was >2 kb, 3' extension
      frequency increased by as much as 10-fold. Excess wild-type Rad51 did not
      increase the average 3' extension tract length. Analysis of cell lines expressing
      N-terminally FLAG-tagged Rad51 polymerization mutants F86E, A89E, or F86E/A89E
      established that the 3' extension process requires Rad51 polymerization activity.
      Mouse hybridoma cells that have reduced Brca2 (Breast cancer susceptibility 2)
      due to stable expression of small interfering RNA show a significant reduction in
      3' extension efficiency; expression of wild-type human BRCA2, but not a BRCA2
      variant devoid of BRC repeats 1-8, rescues the 3' extension defect in these
      cells. Our results suggest that increased Rad51 concentration and homology length
      interact synergistically to promote 3' extension, presumably as a result of
      enhanced Brca2-mediated Rad51 polymerization. 

PMID- 24583582
TI  - Fisher's geometrical model emerges as a property of complex integrated phenotypic
      networks.
AB  - Models relating phenotype space to fitness (phenotype-fitness landscapes) have
      seen important developments recently. They can roughly be divided into
      mechanistic models (e.g., metabolic networks) and more heuristic models like
      Fisher's geometrical model. Each has its own drawbacks, but both yield testable
      predictions on how the context (genomic background or environment) affects the
      distribution of mutation effects on fitness and thus adaptation. Both have
      received some empirical validation. This article aims at bridging the gap between
      these approaches. A derivation of the Fisher model "from first principles" is
      proposed, where the basic assumptions emerge from a more general model, inspired
      by mechanistic networks. I start from a general phenotypic network relating
      unspecified phenotypic traits and fitness. A limited set of qualitative
      assumptions is then imposed, mostly corresponding to known features of phenotypic
      networks: a large set of traits is pleiotropically affected by mutations and
      determines a much smaller set of traits under optimizing selection. Otherwise,
      the model remains fairly general regarding the phenotypic processes involved or
      the distribution of mutation effects affecting the network. A statistical
      treatment and a local approximation close to a fitness optimum yield a landscape
      that is effectively the isotropic Fisher model or its extension with a single
      dominant phenotypic direction. The fit of the resulting alternative distributions
      is illustrated in an empirical data set. These results bear implications on the
      validity of Fisher's model's assumptions and on which features of mutation
      fitness effects may vary (or not) across genomic or environmental contexts. 

PMID- 24583583
TI  - Efficient imputation of missing markers in low-coverage genotyping-by-sequencing
      data from multiparental crosses.
AB  - We consider genomic imputation for low-coverage genotyping-by-sequencing data
      with high levels of missing data. We compensate for this loss of information by
      utilizing family relationships in multiparental experimental crosses. This nearly
      quadruples the number of usable markers when applied to a large rice Multiparent
      Advanced Generation InterCross (MAGIC) study. 

PMID- 24583584
TI  - [Quantitative and qualitative analyses for characteristics of the clock drawing
      in Alzheimer's disease].
AB  - We analyzed the results of the clock drawing test (CDT) in patients with
      Alzheimer's disease (AD) by quantitative and qualitative methods to evaluate its
      significance for cognitive function screening. We administered the CDT and mini
      mental state examination (MMSE) to a total of 156 AD patients, and CDT
      performance was scored quantitatively in accordance with the method by Freedman,
      while the CDT error types were qualitatively classified by Rouleau's method. We
      divided AD patients into three groups by their MMSE total score (A: 23 <=, B:
      18~22, C: <= 17). The mean total scores of CDT and MMSE in AD were 11.5 +/- 3.4
      and 19.8 +/- 4.7, respectively, and the total CDT scores showed significant
      positive correlation with the total MMSE scores (r = 0.450). Fewer than 80% of
      subjects drew the clock correctly for 8 out of 15 sub-items, and fewer were able
      to correctly draw clock hands than could correctly draw numbers, contour or a
      center. In analysis of CDT qualitative error types, the most common error types
      were spatial and/or planning deficit (SPD) (28.2%), and conceptual deficit (CD)
      (23.7%), which suggested visuospatial impairments and semantic impairments play
      essential roles in AD patients' poor clock drawings. The frequency of CD and SPD
      error types significantly increased as severity of cognitive function worsened (p
      < 0.001, p < 0.05, respectively), and those of stimulus-bound response and
      perseveration had tendency to increase as severity of cognitive function. The
      present study suggests that CDT is a useful screening method not only for the
      impairment of cognitive function and the severity of cognitive dysfunction, but
      also for identification of specific cognitive function impairments in AD
      patients.

PMID- 24583585
TI  - [Central pontine myelinolysis developed during alcohol withdrawal in a chronic
      alcoholic with hyperosmolar hyperglycemic state].
AB  - We present a 46-year-old man with central pontine myelinolysis (CPM). He had been
      diagnosed with diabetes mellitus and chronic pancreatitis. He had drunk more than
      1.2 l of Japanese sake daily for 20 years and more. He developed slight reduction
      of consciousness, dysarthria and truncal ataxia 7 days after he stopped drinking.
      The laboratory data on admission showed hyperosmolar hyperglycemic state,
      according to the following findings; glucose 1,058 mg/dl, serum osmolality 328
      mOsm/l and serum sodium 119 mEq/l. According as administration of acetic Ringer's
      solution and insulin injection, the laboratory data 14 hours after admission
      showed glucose 235 mg/dl, serum osmolality 290 mOsm/l and serum sodium 131 mEq/l.
      The initial diffusion weighted images (DWI) on MRI revealed a small high signal
      intensity spot in the pons. The second DWI after 14 days revealed a trident
      shaped hyperintensity in the pons that was compatible with CPM. His symptoms
      showed no remarkable changes, but susceptibility weighted images of MRI after 4
      months revealed low signal intensity area in the CPM lesion that indicated
      pontine hemorrhage. We speculate that marked fluctuation of serum osmotic
      pressure associated with the rapid change of the serum glucose had a significant
      role in the pathogenesis of the present case. Therefore, we recommend gradual
      correction of serum glucose and serum osmolality to maintain less than 12
      mEq/l/day as correction of chronic hyponatremia in to prevent and ameliorate
      pathologic condition of CPM.

PMID- 24583586
TI  - [A case of colchicine-responsive Mollaret's meningitis with MEFV gene mutation].
AB  - A 66-year-old woman was admitted to our hospital with recurrent meningitis. She
      presented with 10 episodes of meningitis in 10 months. Examination of
      cerebrospinal fluid demonstrated pleocytosis, with neutrophils dominant at the
      early stage, and lymphocytes dominant at the late stage. Mollaret cells were
      found and the level of IL-6 was increased in cerebrospinal fluid. Several
      antibiotics and antiviral agents failed to prevent relapse. However, colchicine
      therapy successfully prevented the recurrence of meningitis. Genetic testing for
      familial Mediterranean fever (FMF) showed a mutation in the MEFV gene. It is
      difficult to diagnose the cause of Mollaret's meningitis in some patients. FMF,
      neuro-Behcet's disease, and neuro-Sweet disease should be included in the
      differential diagnosis of recurrent meningitis. In addition, colchicine therapy
      can prevent the relapse of meningitis in such cases.

PMID- 24583587
TI  - [A case of possible neuro-Sweet disease with prolonged disturbance of
      consciousness and no dermal lesion during the course of dementia].
AB  - The patient was a 58-year-old man with 1-year history of cognitive decline, which
      was diagnosed as Alzheimer's disease in another hospital. He was admitted to our
      hospital for extreme fatigue, weight loss, and dysphagia, subsequent to the left
      peripheral facial paresis. Brain magnetic resonance (MR) imaging showed bilateral
      diffuse white matter lesions and hippocampal atrophy. After admission, he
      presented with sudden high fever, recurrent exacerbations of consciousness, and
      increased C-reactive protein level with marked neutrophilia, with the result that
      he underwent mechanical ventilation. Routine cerebrospinal fluid findings at the
      exacerbation were normal i.e. 4.7 cells/mm(3), 40 mg/dl of protein, but IL-6
      concentration was mildly elevated to 22.2 pg/ml. After confirming the positivity
      of HLA (human leukocyte antigen) B54 and Cw1, we administered steroid to him and
      his physical activity and state of consciousness significantly improved. During
      the course of treatment, dermal lesion characterisitic of Sweet disease was
      absent. We diagnosed this case was possible neuroSweet disease proposed by
      Hisanaga in 2005.

PMID- 24583588
TI  - [Acute disseminated encephalomyelitis following influenza vaccination: report of
      a case with callosal disconnection syndrome].
AB  - We present a case of callosal disconnection syndrome as a rare manifestation of
      acute disseminated encephalomyelitis (ADEM). A dextral 48-year-old Japanese woman
      received trivalent inactivated influenza vaccine in mid-November 2011. Twenty
      days later, she was found to be in a daze. Subsequently, she developed abnormal
      behavior and gait disturbance, and she was disoriented regarding time and place.
      Nystagmus and abnormal ocular movements were absent. Upper limb power was normal,
      whereas her lower limbs were mildly weak. Tendon reflexes were normally evoked
      without pathological reflexes. There was no sensory impairment. Serum CRP levels
      were slightly elevated; other routine laboratory tests, thyroid functions, and
      vitamin B1 levels were within the normal range. Cerebrospinal fluid examination
      revealed that it was acellular with a protein level of 54 mg/dl and high myelin
      basic protein level. Fluid-attenuated inversion recovery MR images revealed a
      large hyperintense lesion in the corpus callosum, but the lower part of the
      splenium was spared. Flow voids were observed in the pericallosal arteries. She
      was diagnosed with post-vaccination ADEM and vigorously treated with an
      intravenous infusion of methylprednisolone (1 g/day for 6 days) and
      immunoglobulin (1.2 g/kg). Gait disturbance and disorientation rapidly improved;
      however, tactile anomia, ideomotor apraxia, ideational apraxia, and agraphia of
      the left hand were present one month after onset. She had no aphasia or
      alexia.Interestingly, the patient's left unilateral agraphia was more prominent
      in kana than kanji (an article in Japanese text) for polysyllabic words, whereas
      she could write kana characters to dictation. Changes in the sequential order of
      kana characters within a word were observed. These findings were similar to those
      observed in pure agraphia associated with lesions in the posterior part of the
      left middle frontal gyrus. Thus, an interhemispheric mechanism is probably
      involved in the selection and arrangement of kana characters to form words.

PMID- 24583589
TI  - [A case of isolated mycobacterial focal meningitis diagnosed on brain and
      meningeal biopsy].
AB  - A 76-year-old woman was admitted to our hospital because of convulsions that
      developed after a 1-month history of progressive right-leg palsy. MRI showed
      thickening of the meninges with gadolinium enhancement in the left parietal lobe
      and it revealed pia-subarachnoid space pattern. A lumbar puncture was performed,
      and cerebrospinal fluid analysis revealed no abnormality. Her serum adenosine
      deaminase level was elevated (28.7 IU/l). The results of serum cultures were
      normal. To differentially diagnose collagen disease, infection, malignancy, and
      inflammation of uncommon causes, we conducted brain and meningeal biopsies on the
      15th hospital day. Histopathological examination of the brain tissue showed
      mainly necrosis and inflammation. There was severe pachymeningeal thickening
      without necrosis. Although it was difficult to reach a definitive diagnosis, a
      tissue sample taken from under the leptomeninges tested positive for
      mycobacterium on Ziehl-Neelsen staining. The results of polymerase chain reaction
      for mycobacterium were negative in the meningeal tissue. The patient received
      anti-tuberculous drugs, anti-nontuberculous mycobacteriosis drugs, and
      corticosteroids to treat Mycobacterium tuberculosis and nontuberculous
      mycobacterium. After starting treatment, the findings on magnetic resonance
      imaging improved dramatically, and no convulsions occurred during
      hospitalization. She was discharged on the 153rd hospital day without any
      neurological deficit. Because previous studies have reported that isolated
      mycobacterium meningitis is a diagnostically challenging condition, brain and
      meningeal biopsies should be considered in patients with gadolinium enhancement
      in the meninges.

PMID- 24583590
TI  - [A case of Lyme neuroborreliosis coexistent with T-cell lymphoma].
AB  - An 80-year-old Japanese man developed sensory disturbance of his extremities. One
      week after the onset of sensory disturbance, he also developed bilateral facial
      nerve palsy, weakness of the extremities, vesicorectal disturbance, general
      fatigue, and syndrome of inappropriate antidiuretic hormone secretion (SIADH).
      His symptoms worsened gradually. Despite the absence of apparent tick bite and
      characteristic skin lesions, we suspected Lyme neuroborreliosis (LNB) because of
      pleocytosis and elevated protein levels in the cerebrospinal fluid (CSF), in
      addition to the aforementioned symptoms. After combined administration of
      antibiotics and steroids, his symptoms improved rapidly. CSF showed highly
      elevated levels of the chemokine CXCL-13 and his serum was positive for IgM
      against Borrelia afzelii. Therefore, we diagnosed him as having LNB. He developed
      an exacerbation of SIADH and generalized fatigue during the course of LNB. His
      condition deteriorated despite further administration of antibiotics and
      steroids. Bone marrow aspiration revealed the presence of medium- to large-sized
      atypical lymphoma cells and lymphoma cells positive for CD8 but negative for
      CD45. Therefore, we diagnosed T-cell lymphoma. In recent years, an association
      between Borrelial infection and lymphoma development has been suspected. Borrelia
      afzelii infection may have been involved in the development of T-cell lymphoma in
      this case.

PMID- 24583591
TI  - [Cervical cord infarction associated with unilateral vertebral artery dissection
      due to golf swing].
AB  - A-68-year-old man experienced nuchal pain and bilateral shoulder weakness that
      occurred suddenly after he performed a golf swing. He was conscious. His cranial
      nerves were normal, but bilateral deltoid and biceps muscle strengths weakened.
      Magnetic resonance image (MRI) showed no brain stem infarctions or cervical
      epidural hematoma. We tentatively diagnosed him with concussion of the spinal
      cord because of mild recovery of his bilateral upper limb weakness after several
      hours; he was later discharged. The next day, he suddenly developed serious
      tetraplegia and was admitted to the emergency department. His breathing was
      controlled by a respirator as he had expectoration difficulty and respiratory
      muscle paralysis. A lesion in the cervical cord became apparent on MRI; the right
      vertebral artery was not detected on magnetic resonance angiography. Cervical MRI
      showed the intimal flap and a lack of flow void in the right vertebral artery.
      These findings revealed a right vertebral artery dissection. Cervical cord
      infarction due to unilateral vertebral artery dissection is rarer than posterior
      cerebral infarction due to the same pathogenesis; however, some such cases have
      been reported. We consider the present case to be caused by cervical cord
      infarction associated with unilateral vertebral artery dissection resulting from
      golf swing.

PMID- 24583592
TI  - [Orbital apex syndrome without MRI lesion caused by ANCA-associated vasculitis].
AB  - A 73-year-old man developed double vision and a progressive loss of visual acuity
      of the left eye over one week. Examination showed disturbances of the left II,
      III, IV, and VI cranial nerves, that is, an orbital apex syndrome. A brain MRI
      showed abnormal T2-high signals in the right maxillary sinus and the left mastoid
      cells without abnormalities in the left orbital apex and the surroundings.
      Laboratory examination showed an elevated erythrocyte sedimentation rate and a
      positive perinuclear anti-neutrophil cytoplasmic antibody (MPO-ANCA). After two
      courses of methyl-prednisolone pulse treatment, his external ophthalmoplegia
      fully recovered and he regained his left eye's sight. MPO-ANCA was negative and
      MRI abnormalities were disappeared after treatment. Two years later, the patient
      developed upper respiratory symptoms associated with an elevation of MPO-ANCA
      titer, and rapidly progressive renal failure. Renal biopsy specimen showed
      fibrinoid necrosis with periarteriolar neutrophil infiltration, which suggested
      that the patient suffered from ANCA-associated vasculitis probably of Wegener's
      granulomatosis or microscopic polyarteritis. ANCA-associated vasculitis may
      present with a focal neurological syndrome such as the orbital apex syndrome
      without a lesion detectable with MRI.

PMID- 24583593
TI  - [A case of transient ischemic attack of hemodynamic origin induced by
      postprandial hypotension].
AB  - An 82-year-old man had a transient ischemic attack (TIA) with symptoms of
      consciousness disturbance and right hemiparesis while resting in a sitting
      position after breakfast. His symptoms improved around 1 h after onset when he
      lied in a supine position and received intravenous hydration. Duplex carotid
      ultrasonography revealed severe stenosis of the left common carotid artery. A
      decrease in the brain perfusion reserve was confirmed by acetazolamide-stress
      brain perfusion scintigraphy. Moreover, ambulatory blood pressure monitoring
      revealed a reduction in systolic blood pressure below 90 mmHg after each meal,
      indicating postprandial hypotension (PPH). The PPH was improved by oral
      administration of alpha-glucosidase inhibitor without any subsequent recurrences
      of TIA. The patient was diagnosed with TIA of hemodynamic origin that was induced
      by PPH and exhibited severe carotid stenosis. PPH is common in elderly people,
      and it should be recognized as a significant trigger for ischemic cerebrovascular
      disease.

PMID- 24583599
TI  - Sequential inoculation versus co-inoculation in Cabernet Franc wine fermentation.
AB  - A study has been carried out in order to determine the effect of the lactic acid
      bacteria inoculation time on the kinetic of vinification and on chemical and
      sensory characteristics of Cabernet Franc wines. Traditional vinifications, with
      lactic acid bacteria inoculated after completion of alcoholic fermentation were
      compared with vinifications where yeast and bacteria were co-inoculated at the
      beginning of vinification. One commercial yeast strain and an autochthonous
      Oenococcus oeni strain (C22L9), previously identified and selected at our
      laboratory, were used. Monitoring of alcoholic and malolactic fermentations was
      carried out by yeast and lactic acid bacteria counts and by measuring l-malic
      acid concentration. Wines were chemically characterized and analysed for volatile
      compounds content. A sensory analysis, consisting of a descriptive and a
      triangular test, was also carried out. Results from this study showed that the
      concurrent yeast/bacteria inoculation of musts at the beginning of vinification
      produced a reduction in duration of the process without an excessive increase in
      volatile acidity. Differences in volatile compounds content and the corresponding
      impact on the sensorial profile of wines were also displayed. These results
      suggest that co-inoculation is a worthwhile alternative for winemaking of
      Cabernet Franc wines, if compared with traditional post-alcoholic fermentation
      lactic acid bacteria inoculation. 

PMID- 24583600
TI  - Facile nucleation of gold nanoparticles on graphene-based thin films from Au144
      molecular precursors.
AB  - We demonstrate a facile and cost effective method to obtain gold nanoparticles on
      graphene by dispersing Au144 molecular nanoclusters by spin coating them in thin
      layers on graphene-based films and subsequent annealing in a controlled
      atmosphere. The graphene-based thin films used for these experiments are prepared
      by solvent-assisted exfoliation of graphite in water in the presence of
      ribonucleic acid as a surfactant and by subsequent vacuum filtration of the
      resulting graphene-containing suspensions. Not only is this method easily
      reproducible, but it leads to gold nanoparticles that are not dependent in size
      on the number of graphene layers beneath them. This is a distinct advantage over
      other methods. Plasmonic effects have been detected in our gold nanoparticle
      decorated graphene layers, indicating that these thin films may be useful in
      applications such as plasmonic solar cells and optical memory devices.

PMID- 24583601
TI  - A differential role for CXCR4 in the regulation of normal versus malignant breast
      stem cell activity.
AB  - C-X-C chemokine receptor type 4 (CXCR4) is known to regulate lung, pancreatic and
      prostate cancer stem cells. In breast cancer, CXCR4 signalling has been reported
      to be a mediator of metastasis, and is linked to poor prognosis. However its role
      in normal and malignant breast stem cell function has not been investigated.
      Anoikis resistant (AR) cells were collected from immortalised (MCF10A, 226L) and
      malignant (MCF7, T47D, SKBR3) breast cell lines and assessed for stem cell
      enrichment versus unsorted cells. AR cells had significantly higher mammosphere
      forming efficiency (MFE) than unsorted cells. The AR normal cells demonstrated
      increased formation of 3D structures in Matrigel compared to unsorted cells. In
      vivo, SKBR3 and T47D AR cells had 7- and 130-fold enrichments for tumour
      formationrespectively, compared with unsorted cells. AR cells contained
      significantly elevated CXCR4 transcript and protein levels compared to unsorted
      cells. Importantly, CXCR4 mRNA was higher in stem cell-enriched CD44+/CD24-
      patient-derived breast cancer cells compared to non-enriched cells. CXCR4
      stimulation by its ligand SDF-1 reduced MFE of the normal breast cells lines but
      increased the MFE in T47D and patient-derived breast cancer cells. CXCR4
      inhibition by AMD3100 increased stem cell activity but reduced the self-renewal
      capacity of the malignant breast cell line T47D. CXCR4+ FACS sorted MCF7 cells
      demonstrated a significantly increased MFE compared with CXCR4- cells. This
      significant increase in MFE was further demonstrated in CXCR4 over-expressing
      MCF7 cells which also had an increase in self-renewal compared to parental cells.
      A greater reduction in self-renewal following CXCR4 inhibition in the CXCR4 over
      expressing cells compared with parental cells was also observed. Our data
      establish for the first time that CXCR4 signalling has contrasting effects on
      normal and malignant breast stem cell activity. Here, we demonstrate that CXCR4
      signalling specifically regulates breast cancer stem cell activities and may
      therefore be important in tumour formation at the sites of metastases. 

PMID- 24583602
TI  - Mode of action classification of chemicals using multi-concentration time
      dependent cellular response profiles.
AB  - In this paper, we present a new statistical pattern recognition method for
      classifying cytotoxic cellular responses to toxic agents. The advantage of the
      proposed method is to quickly assess the toxicity level of an unclassified toxic
      agent on human health by bringing cytotoxic cellular responses with similar
      patterns (mode of action, MoOA) into the same class. The proposed method is a
      model-based hierarchical classification approach incorporating principal
      component analysis (PCA) and functional data analysis (FDA). The cytotoxic cell
      responses are represented by multi-concentration time-dependent cellular response
      profiles (TCRPs) which are dynamically recorded by using the xCELLigence real
      time cell analysis high-throughput (RTCA HT) system. The classification results
      obtained using our algorithm show satisfactory discrimination and are validated
      using biological facts by examining common chemical mechanisms of actions with
      treatment on human hepatocellular carcinoma cells (HepG2). 

PMID- 24583603
TI  - Affinity of HIV-1 antibody 2G12 with monosaccharides: a theoretical study based
      on explicit and implicit water models.
AB  - In order to develop potential ligands to HIV-1 antibody 2G12 toward HIV-1
      vaccine, binding mechanisms of the antibody 2G12 with the glycan ligand of D
      mannose and D-fructose were theoretically examined. D-Fructose, whose molecular
      structure is slightly different from D-mannose, has experimentally shown to have
      stronger binding affinity to the antibody than that of D-mannose. To clarify the
      nature of D-fructose's higher binding affinity over D-mannose, we studied
      interaction between the monosaccharides and the antibody using ab initio fragment
      molecular orbital (FMO) method considering solvation effect as implicit model
      (FMO-PCM) as well as explicit water model. The calculated binding free energies
      of the glycans were qualitatively well consistent with the experimentally
      reported order of their affinities with the antibody 2G12. In addition, the FMO
      PCM calculation elucidated the advantages of D-fructose over D-mannose in the
      solvation energy as well as the entropic contribution term obtained by MD
      simulations. The effects of explicit water molecules observed in the X-ray
      crystal structure were also scrutinized by means of FMO methods. Significant pair
      interaction energies among D-fructose, amino acids, and water molecules were
      uncovered, which indicated contributions from the water molecules to the strong
      binding ability of D-fructose to the antibody 2G12. These FMO calculation results
      of explicit water model as well as implicit water model indicated that the strong
      binding of D-fructose over D-mannose was due to the solvation effects on the D
      fructose interaction energy.

PMID- 24583604
TI  - ISDTool: a computational model for predicting immunosuppressive domain of HERVs.
AB  - Human endogenous retroviruses (HERVs) have been found to act as etiological
      cofactors in several chronic diseases, including cancer, autoimmunity and
      neurological dysfunction. Immunosuppressive domain (ISD) is a conserved region of
      transmembrane protein (TM) in envelope gene (env) of retroviruses. In vitro and
      vivo, evidence has shown that retroviral TM is highly immunosuppressive and a
      synthetic peptide (CKS-17) that shows homology to ISD inhibits immune function.
      ISD is probably a potential pathogenic element in HERVs. However, only less than
      one hundred ISDs of HERVs have been annotated by researchers so far, and
      universal software for domain prediction could not achieve sufficient accuracy
      for specific ISD. In this paper, a computational model is proposed to identify
      ISD in HERVs based on genome sequences only. It has a classification accuracy of
      97.9% using Jack-knife test. 117 HERVs families were scanned with the model, 1002
      new putative ISDs have been predicted and annotated in the human chromosomes.
      This model is also applicable to search for ISDs in human T-lymphotropic virus
      (HTLV), simian T-lymphotropic virus (STLV) and murine leukemia virus (MLV)
      because of the evolutionary relationship between endogenous and exogenous
      retroviruses. Furthermore, software named ISDTool has been developed to
      facilitate the application of the model. Datasets and the software involved in
      the paper are all available at
      https://sourceforge.net/projects/isdtool/files/ISDTool-1.0.

PMID- 24583605
TI  - 1,2,3-Triazole-containing derivatives of rupestonic acid: click-chemical
      synthesis and antiviral activities against influenza viruses.
AB  - Two series of rupestonic acid derivatives, (1-substituted-1H-1,2,3-triazol-4
      yl)methyl 2-((5R,8S,8aS)-3,8-dimethyl-2-oxo-1,2,4,5,6,7,8,8a-octahydroazulen-5
      yl)acrylate and N-(1-substituted-1H-1,2,3-triazol-4-yl)methyl 2-((5R,8S,8aS)-3,8
      dimethyl-2-oxo-1,2,4,5,6,7,8,8a-octahydroazulen-5-yl)acrylamide were easily and
      efficiently synthesized via click chemistry. These compounds were tested for
      their in vitro activities against various strains of influenza A virus (H1N1,
      oseltamivir resistant H1N1, H3N2) and influenza B virus. The results showed that
      nine compounds were active against the H1N1 strain of influenza A virus and among
      them the best one 14a, was as active as the reference drugs, Oseltamivir and
      Ribavirin. Some of them were also active on the Oseltamivir resistant H1N1
      strain. In regards to influenza B virus, twenty-one compounds over thirty were
      active and seven of them 7b, 8b, 9b, 10a, 11b, 12b, 13b showed better activity
      than Ribavirin. The structure-activity relationship of these compounds is
      discussed on the basis of each type of the viruses studied. Furthermore, four
      best representative compounds 7b, 10a, 12b and 14a were evaluated in a plaque
      assay experiment using MDCK cells and RBV as control compound and the results
      showed that 7b, 10a and 12b were better than RBV in inhibiting plaque formation,
      in good accordance with their anti-influenza B activities.

PMID- 24583606
TI  - Cytotoxicity and antimicrobial activities of green synthesized silver
      nanoparticles.
AB  - Bio-inspired silver nanoparticles are synthesized using Malus domestica (apple)
      extract. Polyphenols present in the apple extract act as a reducing and capping
      agent to produce the silver nanoparticles. UV-Visible analysis shows the surface
      plasmon resonance (SPR) absorption at 420 nm. The FTIR analysis was used to
      identify the functional groups responsible for the bio-reduction of silver ion.
      The XRD and HRTEM images confirm the formation of silver nanoparticles. The
      minimal inhibitory concentration (MIC) of silver nanoparticles was recorded
      against most of the bacteria and fungus. Further, MCF-7 human breast
      adenocarcinoma cancer cell line was employed to observe the efficacy of cancer
      cell killing.

PMID- 24583607
TI  - Imidazolylchromanones containing non-benzylic oxime ethers: synthesis and
      molecular modeling study of new azole antifungals selective against Cryptococcus
      gattii.
AB  - A series of imidazolylchromanone oximes containing phenoxyethyl ether moiety, as
      found in omoconazole, were synthesized and evaluated against yeasts (Candida
      albicans and Cryptococcus gattii) and filamentous fungi (Aspergillus fumigatus
      and Exophiala dermatitidis). Although the title compounds showed marginal
      activity against filamentous fungi but all of them exhibited potent activity
      against C. gattii (MIC values <=4 MUg/mL). Among them, (3-chlorophenoxy)ethyl
      analog 7c with MIC value of 0.5 MUg/mL was the most potent compound. Further
      molecular docking studies provided a better insight into the binding of designed
      compounds within the homology modeled active site of CnCYP51 (Cryptococcus CYP51
      14alpha-demethylase).

PMID- 24583608
TI  - Use of naturalized coagulants in removing laundry waste surfactant using various
      unit processes in lab-scale.
AB  - This lab-scale experiment is aimed at demonstrating a treatment system for
      purification and reuse of laundry rinsing water generated from households. The
      main objective of the study is to compare the efficiencies of various natural
      coagulants in removing laundry waste surfactants and other major pollutants from
      the laundry rinsing water. The treatment system consists of Coagulation
      Flocculation, Sand filtration and Granular Activated Carbon (GAC) adsorption.
      Four experiments were conducted in batch process by varying the coagulants
      (Nirmali seed and Pectin extracted from pith of Orange peel). Coagulants have
      been selected due to their local availability at affordable cost and technical
      feasibility. From the study it is concluded that laundry rinsing water polluted
      with high turbidity and anionic surfactant treated with Nirmali seeds as
      coagulant at a retention time of 24 h gives the best results. The treatment
      system where Orange peel pectin is used as coagulant at a retention time of 24 h
      is found to be the most efficient one based on the weighted factor. Hence the
      treatment of laundry rinsing water by aforesaid combination results in better
      water quality. 

PMID- 24583610
TI  - Alteration of the intestinal microbiota as a cause of and a potential therapeutic
      option in irritable bowel syndrome.
AB  - The intestinal microbiota forms a complex ecosystem that is in close contact with
      its host and has an important impact on health. An increasing number of disorders
      are associated with disturbances in this ecosystem. Also patients suffering from
      irritable bowel syndrome (IBS) show an altered composition of their gut
      microbiota. IBS is a multifactorial chronic disorder characterised by various
      abdominal complaints and a worldwide prevalence of 10-20%. Even though its
      aetiology and pathophysiology are complex and not well understood, it is widely
      accepted that aberrations along the microbe-gut-brain axis are involved. In this
      review, it will be discussed how exogenous factors, e.g. antibiotics, can cause
      disbalance in the intestinal microbiota and thereby contribute to the development
      of IBS. In addition, several new IBS treatment options that aim at re
      establishing a healthy, beneficial ecosystem will be described. These include
      antibiotics, probiotics, prebiotics and faecal transplantation. 

PMID- 24583609
TI  - Detection limits and cost comparisons of human- and gull-associated conventional
      and quantitative PCR assays in artificial and environmental waters.
AB  - Some molecular methods for tracking fecal pollution in environmental waters have
      both PCR and quantitative PCR (qPCR) assays available for use. To assist managers
      in deciding whether to implement newer qPCR techniques in routine monitoring
      programs, we compared detection limits (LODs) and costs of PCR and qPCR assays
      with identical targets that are relevant to beach water quality assessment. For
      human-associated assays targeting Bacteroidales HF183 genetic marker, qPCR LODs
      were 70 times lower and there was no effect of target matrix (artificial
      freshwater, environmental creek water, and environmental marine water) on PCR or
      qPCR LODs. The PCR startup and annual costs were the lowest, while the per
      reaction cost was 62% lower than the Taqman based qPCR and 180% higher than the
      SYBR based qPCR. For gull-associated assays, there was no significant difference
      between PCR and qPCR LODs, target matrix did not effect PCR or qPCR LODs, and PCR
      startup, annual, and per reaction costs were lower. Upgrading to qPCR involves
      greater startup and annual costs, but this increase may be justified in the case
      of the human-associated assays with lower detection limits and reduced cost per
      sample. 

PMID- 24583611
TI  - Impact of prebiotics and probiotics on skin health.
AB  - This review discusses the role of pre- and probiotics with respect to improving
      skin health by modulating the cutaneous microbiota. The skin ecosystem is a
      complex environment covered with a diverse microbiota community. These are
      classified as either transient or resident, where some are considered as
      beneficial, some essentially neutral and others pathogenic or at least have the
      capacity to be pathogenic. Colonisation varies between different parts of the
      body due to different environmental factors. Pre- and probiotic beneficial
      effects can be delivered topically or systemically (by ingestion). The pre- and
      probiotics have the capacity to optimise, maintain and restore the microbiota of
      the skin in different ways. Topical applications of probiotic bacteria have a
      direct effect at the site of application by enhancing the skin natural defence
      barriers. Probiotics as well as resident bacteria can produce antimicrobial
      peptides that benefit cutaneous immune responses and eliminate pathogens. In
      cosmetic formulations, prebiotics can be applied to the skin microbiota directly
      and increase selectively the activity and growth of beneficial 'normal' skin
      microbiota. Little is known about the efficacy of topically applied prebiotics.
      Nutritional products containing prebiotics and/or probiotics have a positive
      effect on skin by modulating the immune system and by providing therapeutic
      benefits for atopic diseases. This review underlines the potential use of pre-
      and probiotics for skin health. 

PMID- 24583612
TI  - Gut ecosystem: how microbes help us.
AB  - The human gut houses one of the most complex and abundant ecosystems composed of
      up to 1013-1014 microorganisms. Although the anthropocentric concept of life has
      concealed the function of microorganisms inside us, the important role of gut
      bacterial community in human health is well recognised today. Moreover, different
      microorganims, which are commonly present in a large diversity of food products,
      transit through our gut every day adding in some cases a beneficial effect to our
      health (probiotics). This crosstalk is concentrated mainly in the intestinal
      epithelium, where microbes provide the host with essential nutrients and
      modulation of the immune system. Furthermore, microorganisms also display
      antimicrobial activities maintaining a gut ecosystem stable. This review
      summarises some of the recent findings on the interaction of both commensal and
      probiotic bacteria with each other and with the host. The aim is to highlight the
      cooperative status found in healthy individuals as well as the importance of this
      crosstalk in the maintenance of human homeostasis. 

PMID- 24583614
TI  - Task shifting for the delivery of pediatric antiretroviral treatment: a
      systematic review.
AB  - BACKGROUND: Pediatric antiretroviral treatment coverage in resource-limited
      settings continues to lag behind adults. Task shifting is an effective approach
      broadly used for adults, which some countries have also adopted for children, but
      implementation is limited by lack of confidence and skills among nonspecialist
      staff. METHODS: A systematic review was conducted by combining key terms for task
      shifting, antiretroviral therapy (ART), and children. Five databases and two
      conferences were searched from inception till August 01, 2013. RESULTS: Eight
      observational studies provided outcome data for 11,828 children who received ART
      from nonphysician providers across 10 countries in sub-Saharan Africa. The
      cumulative pooled proportion of deaths was 3.2% [95% confidence interval (CI):
      2.0 to 4.5] at 6 months, 4.6% (95% CI: 2.1 to 7.1) at 12 months, 6.2% (95% CI:
      3.7 to 8.8) at 24 months, and 5.9% (95% CI: 3.5 to 8.3) at 36 months. Mortality
      and loss to follow-up in task-shifting programs were comparable to those reported
      by programs providing doctor- or specialist-led care. CONCLUSIONS: Our review
      suggests that task shifting of ART care can result in outcomes comparable to
      routine physician care, and this approach should be considered as part of a
      strategy to scale-up pediatric treatment. Specialist care will remain important
      for management of sick patients and complicated cases. Further qualitative
      research is needed to inform optimal implementation of task shifting for
      pediatric patients.

PMID- 24583613
TI  - Immune responses in Ugandan women infected with subtypes A and D HIV using the
      BED capture immunoassay and an antibody avidity assay.
AB  - INTRODUCTION: Analysis of samples from Uganda using serologic HIV incidence
      assays reveal that individuals with subtype D infection often have weak humoral
      immune responses to HIV infection. It is unclear whether this reflects a poor
      initial response to infection or a waning antibody response later in infection.
      MATERIALS AND METHODS: Samples (N = 2614) were obtained from 114 women aged 18-45
      years in the Ugandan Genital Shedding and Disease Progression Study cohort (2001
      2009; 82 subtype A, 32 subtype D; median 23 samples/women, range 3-41 samples,
      median follow-up of 6.6 years). Samples were analyzed using the BED capture
      immunoassay (cutoff, 0.8 OD-n) and the avidity assay (cutoff, 90% Avidity Index).
      Antibody maturation was assessed by having the BED capture enzyme immunoassay
      (BED-CEIA) or avidity value exceed the assay cutoff 1 or 2 years after infection.
      The waning antibody response was measured by having the BED-CEIA or avidity value
      fall >20% below the maximum value. RESULTS: For the BED-CEIA, 8 women with
      subtype A infection and 3 women with subtype D infection never progressed
      previously the cutoff value (median, 5.9 years follow-up after infection). Six
      women with subtype D infection never achieved an avidity index >90%. Subtype did
      not impact the proportion of women whose assay values regressed by >20% of the
      maximal value (for BED-CEIA: 33% for A, 41% for D, P = 0.51; for avidity: 1% for
      A, 6% for D, P = 0.19). DISCUSSION: The higher frequency of misclassification of
      individuals with long-term subtype D infection as recently infected using
      serologic incidence assays reflects a weak initial antibody response to HIV
      infection that is sustained over time.

PMID- 24583615
TI  - Randomized controlled trial of the shang ring versus conventional surgical
      techniques for adult male circumcision: safety and acceptability.
AB  - OBJECTIVE: To compare clinical profiles of Shang Ring versus conventional
      circumcisions. DESIGN: Parallel group open-label randomized controlled trial with
      one-to-one allocations in 2 sites. METHODS: We enrolled HIV-negative men aged 18
      54 years in Homa Bay, Kenya, and Lusaka, Zambia and followed them at 2, 7, 14,
      21, 28, 42, and 60 days after Shang Ring versus conventional circumcision. We
      compared the duration of surgery, postoperative pain using a visual analog scale,
      adverse events rates, time to complete wound healing by clinical assessment,
      participant acceptability, and provider preferences between circumcision groups.
      RESULTS: We randomized 200 men to each group; 197 and 201 contributed to the
      Shang Ring and conventional surgery analyses, respectively. Adverse event rates
      were similar between groups. Pain scores at most time points were similar,
      however, the Shang Ring group reported higher scores for worst pain during
      erections (3.5 +/- 1.9 vs. 2.3 +/- 1.7; P < 0.001). Significantly more men were
      satisfied with the cosmetic appearance following Shang Ring male circumcision
      (MC), 95.7% versus 85.9% (P = 0.02) in Kenya, and 96.8% versus 71.3% (P < 0.01)
      in Zambia. Although median time to complete wound healing was 43 days in both
      groups, conventional circumcisions healed on average 5.2 days sooner (P < 0.001).
      Shang Ring procedures took one-third the time of conventional MC, 7 versus 20
      minutes. All circumcision providers preferred the Shang Ring. CONCLUSIONS: Safety
      profiles of the 2 techniques were similar, all MC providers preferred the Shang
      Ring technique, and study participants preferred the Shang Ring's cosmetic
      results. The Shang Ring should be considered for adult MC as programs scale-up.

PMID- 24583616
TI  - Cancer incidence in a Nationwide HIV/AIDS patient cohort in Taiwan in 1998-2009.
AB  - BACKGROUND: The aims of this study were to investigate the cancer incidence and
      risk in HIV/AIDS patients relative to the general population in Taiwan. METHODS:
      Using Taiwan's National Health Insurance Research Database, 15,269 HIV/AIDS
      patients were identified between 1998 and 2009. Gender-specific incidence
      densities (IDs) of both AIDS-defining cancers (ADC) and non-AIDS-defining cancers
      (NADC) after HIV infection were calculated. Age-, sex-, and period-adjusted
      standardized incidence rates (SIRs) were obtained using 1.8 million people from
      the general population as controls. RESULTS: A total of 1117 male and 165 female
      HIV/AIDS patients were diagnosed with cancer. Non-Hodgkin lymphoma (n = 196; ID =
      328.79/100,000 person-years) and cervical cancer (n = 50; ID = 712.08/100,000
      person-years) were the most common ADCs, whereas liver cancer (n = 125; ID =
      184.52/100,000 person-years) and colon cancer (n = 11; ID = 156.66/100,000 person
      years) were the most common NADCs in males and females, respectively. Period
      adjusted gender-specific ADC and NADC rates decreased from more than 1500
      cases/100,000 person-years to less than 500 cases/100,000 person-years (P < 0.001
      for trend). SIRs of ADCs and NADCs also decreased. However, relative to the
      general population, increased SIRs were still seen for most cancers, many of
      which had an infectious etiology. The highest SIRs in ADCs and NADCs were seen in
      Kaposi sarcoma [SIR = 298.0, 95% confidence interval (CI): 258.16 to 343.85] and
      anal cancer (SIR = 19.10, 95% CI: 12.80 to 27.50). CONCLUSION: This study showed
      that although the cancer incidence rates have significantly decreased in the
      highly active antiretroviral therapy era, HIV/AIDS patients were still at
      increased risk of ADCs and most NADCs. Cancer screening, especially for infection
      related NADCs, should therefore be promoted.

PMID- 24583617
TI  - Epidemiology of HIV-1 subtypes among men who have sex with men in Cape Town,
      South Africa.
AB  - OBJECTIVE: Early studies in Cape Town identified independent HIV-1 epidemics,
      with distinct viral subtypes, among men who have sex with men (MSM) and the
      heterosexual population. However, few recent HIV-1 subtype data are available for
      MSM in South Africa. We examined HIV-1 subtypes among MSM in Cape Town. DESIGN:
      Cross-sectional survey. METHODS: Self-identified MSM were recruited from
      geographically and racially disparate communities across Cape Town. Participants
      completed behavioral questionnaires and underwent HIV testing. Virus isolated
      from infected participants underwent complete env gp160 sequencing, and HIV-1
      subtypes were assigned through phylogenetic analysis. RESULTS: In total, 194 HIV
      infected MSM were enrolled: 67% black African, 24% colored, and 9% white men.
      More black African men identified as bisexual or heterosexual compared with other
      races. Overall, 31%-66% of men reported a recent partner of another race. HIV-1
      subtypes were confirmed for 143 participants: 81% were subtype C, 14% B, 1% A1,
      1% F2, and 3 recombinant viruses. Subtype C virus was associated with black
      African race (P = 0.003 compared with colored; P < 0.001 compared with white),
      men who identified as bisexual/heterosexual (P = 0.01), and reported a female
      sexual partner in the last year (P = 0.02). Compared with previous studies, an
      increasing prevalence of subtype C virus was noted among white MSM. CONCLUSIONS:
      This molecular epidemiology study provides novel evidence of sexual network links
      between the heterosexual and MSM epidemics and between historically racially
      disparate communities. These findings provide insights into the drivers of HIV
      epidemics in different population groups and may have implications for prevention
      strategies.

PMID- 24583619
TI  - Clinical importance of hyper-beta-2-microglobulinuria in patients with HIV-1
      infection on tenofovir-containing antiretroviral therapy.

PMID- 24583621
TI  - Functional and morphological characteristics of the retinal and choroidal
      vasculature.
AB  - This review is about vascular endothelial phenotype heterogeneity in the retinal
      and choroidal circulations. It is becoming increasingly clear that the functional
      and structural heterogeneity is present in the retinal and choroidal
      circulations. Differential responses of the vessels to vasoactive substances have
      been shown with intraluminal and extraluminal delivery and in different regions
      of the same vascular bed. Vascular endothelial phenotype is highly heterogenic
      and site-specific, particularly in the retinal and choroidal veins. Updated
      information of such heterogeneity may help us to further understand the control
      mechanisms of the retinal and choroidal circulations which are important in
      compensating for the physiological and pathological challenges faced by these
      vascular beds. The site-specific changes of vascular endothelial phenotype may be
      linked with endothelium dysfunction, and site-specific diseases such as central
      and branch retinal vein occlusion. Endothelial dysfunction has been recognized as
      an initial step for many vascular diseases. Endothelial cells are a strategic and
      valid target for therapeutic intervention. Fundamentally important questions
      regarding the role of vascular endothelial cell function in the eye are
      discussed. 

PMID- 24583620
TI  - A novel IgE-neutralizing antibody for the treatment of severe uncontrolled
      asthma.
AB  - The critical role played by IgE in allergic asthma is well-documented and
      clinically precedented, but some patients in whom IgE neutralization may still
      offer clinical benefit are excluded from treatment with the existing anti-IgE
      therapy, omalizumab, due to high total IgE levels or body mass. In this study, we
      sought to generate a novel high affinity anti-IgE antibody (MEDI4212) with
      potential to treat a broad severe asthma patient population. Analysis of body
      mass, total and allergen-specific IgE levels in a cohort of severe asthmatics was
      used to support the rationale for development of a high affinity IgE-targeted
      antibody therapeutic. Phage display technology was used to generate a human IgG1
      lead antibody, MEDI4212, which was characterized in vitro using binding,
      signaling and functional assay systems. Protein crystallography was used to
      determine the details of the interaction between MEDI4212 and IgE. MEDI4212 bound
      human IgE with an affinity of 1.95 pM and was shown to target critical residues
      in the IgE Cepsilon3 domain critical for interaction with FcepsilonRI. MEDI4212
      potently inhibited responses through FcepsilonRI and also prevented the binding
      of IgE to CD23. When used ex vivo at identical concentration, MEDI4212 depleted
      free-IgE from human sera to levels ~1 log lower than omalizumab. Our results thus
      indicate that MEDI4212 is a novel, high affinity antibody that binds specifically
      to IgE and prevents IgE binding to its receptors. MEDI4212 effectively depleted
      free-IgE from human sera ex vivo to a level (1 IU/mL) anticipated to provide
      optimal IgE suppression in severe asthma patients. 

PMID- 24583622
TI  - Association between individual differences in non-symbolic number acuity and math
      performance: a meta-analysis.
AB  - Many recent studies have examined the association between number acuity, which is
      the ability to rapidly and non-symbolically estimate the quantity of items
      appearing in a scene, and symbolic math performance. However, various
      contradictory results have been reported. To comprehensively evaluate the
      association between number acuity and symbolic math performance, we conduct a
      meta-analysis to synthesize the results observed in previous studies. First, a
      meta-analysis of cross-sectional studies (36 samples, N = 4705) revealed a
      significant positive correlation between these skills (r = 0.20, 95% CI = [0.14,
      0.26]); the association remained after considering other potential moderators
      (e.g., whether general cognitive abilities were controlled). Moreover, a meta
      analysis of longitudinal studies revealed 1) that number acuity may prospectively
      predict later math performance (r = 0.24, 95% CI = [0.11, 0.37]; 6 samples) and
      2) that number acuity is retrospectively correlated to early math performance as
      well (r = 0.17, 95% CI = [0.07, 0.26]; 5 samples). In summary, these pieces of
      evidence demonstrate a moderate but statistically significant association between
      number acuity and math performance. Based on the estimated effect sizes, power
      analyses were conducted, which suggested that many previous studies were
      underpowered due to small sample sizes. This may account for the disparity
      between findings in the literature, at least in part. Finally, the theoretical
      and practical implications of our meta-analytic findings are presented, and
      future research questions are discussed.

PMID- 24583618
TI  - Genetic, transcriptomic, and epigenetic studies of HIV-associated neurocognitive
      disorder.
AB  - The Human Genome Project, coupled with rapidly evolving high-throughput
      technologies, has opened the possibility of identifying heretofore unknown
      biological processes underlying human disease. Because of the opaque nature of
      HIV-associated neurocognitive disorder (HAND) neuropathogenesis, the utility of
      such methods has gained notice among NeuroAIDS researchers. Furthermore, the
      merging of genetics with other research areas has also allowed for application of
      relatively nascent fields, such as neuroimaging genomics, and pharmacogenetics,
      to the context of HAND. In this review, we detail the development of genetic,
      transcriptomic, and epigenetic studies of HAND, beginning with early candidate
      gene association studies and culminating in current "omics" approaches that
      incorporate methods from systems biology to interpret data from multiple levels
      of biological functioning. Challenges with this line of investigation are
      discussed, including the difficulty of defining a valid phenotype for HAND. We
      propose that leveraging known associations between biology and pathology across
      multiple levels will lead to a more reliable and valid phenotype. We also discuss
      the difficulties of interpreting the massive and multitiered mountains of data
      produced by current high-throughput omics assays and explore the utility of
      systems biology approaches in this regard.

PMID- 24583623
TI  - Substrate flexibility and reaction specificity of tropinone reductase-like short
      chain dehydrogenases.
AB  - Annotations of protein or gene sequences from large scale sequencing projects are
      based on protein size, characteristic binding motifs, and conserved catalytic
      amino acids, but biochemical functions are often uncertain. In the large family
      of short-chain dehydrogenases/reductases (SDRs), functional predictions often
      fail. Putative tropinone reductases, named tropinone reductase-like (TRL), are
      SDRs annotated in many genomes of organisms that do not contain tropane
      alkaloids. SDRs in vitro often accept several substrates complicating functional
      assignments. Cochlearia officinalis, a Brassicaceae, contains tropane alkaloids,
      in contrast to the closely related Arabidopsis thaliana. TRLs from Arabidopsis
      and the tropinone reductase isolated from Cochlearia (CoTR) were investigated for
      their catalytic capacity. In contrast to CoTR, none of the Arabidopsis TRLs
      reduced tropinone in vitro. NAD(H) and NADP(H) preferences were relaxed in two
      TRLs, and protein homology models revealed flexibility of amino acid residues in
      the active site allowing binding of both cofactors. TRLs reduced various carbonyl
      compounds, among them terpene ketones. The reduction was stereospecific for most
      of TRLs investigated, and the corresponding terpene alcohol oxidation was
      stereoselective. Carbonyl compounds that were identified to serve as substrates
      were applied for modeling pharmacophores of each TRL. A database of commercially
      available compounds was screened using the pharmacophores. Compounds identified
      as potential substrates were confirmed by turnover in vitro. Thus pharmacophores
      may contribute to better predictability of biochemical functions of SDR enzymes. 

PMID- 24583624
TI  - Risk factors for hypogammaglobulinemia after allo-SCT.

PMID- 24583625
TI  - MTHFR C677T/A1298C genotype: a possible risk factor for liver sinusoidal
      obstruction syndrome.

PMID- 24583626
TI  - Outcomes following second allogeneic haematopoietic transplants using fludarabine
      melphalan conditioning.

PMID- 24583627
TI  - Inhibition of S100A6 induces GVL effects in MLL/AF4-positive ALL in human PBMC
      SCID mice.
AB  - Mixed-lineage leukemia (MLL)/AF4-positive ALL is associated with a poor prognosis
      even after allogeneic hematopoietic SCT (allo-HSCT). We reported previously that
      MLL/AF4-positive ALL shows resistance to TNF-alpha, which is the main factor in
      the GVL effect, by upregulation of S100A6 expression followed by interference
      with the p53-caspase 8-caspase 3 pathway in vitro. We examined whether inhibition
      of S100A6 can induce an effective GVL effect on MLL/AF4-positive ALL in a mouse
      model. MLL/AF4-positive ALL cell lines (SEM) transduced with lentiviral vectors
      expressing both S100A6 siRNA and luciferase (SEM-Luc-S100A6 siRNA) were produced.
      SEM-Luc-S100A6 siRNA cells and SEM-Luc-control siRNA cells were injected into
      groups of five SCID mice (1 * 10(7)/body). After confirmation of engraftment of
      SEM cells by in vivo imaging, the mice in each group were injected with 4.8 *
      10(7) human PBMCs. SEM-Luc-S100A6 siRNA-injected mice showed significantly longer
      survival periods than SEM-Luc-control siRNA-injected mice (P=0.002). SEM-Luc
      S100A6 siRNA-injected mice showed significantly slower tumor growth than those
      injected with SEM-Luc-control siRNA (P<0.0001). These results suggested that
      inhibition of S100A6 may be a promising therapeutic target for MLL/AF4-positive
      ALL in combination with allo-HSCT. 

PMID- 24583629
TI  - Genome-wide analysis of methotrexate pharmacogenomics in rheumatoid arthritis
      shows multiple novel risk variants and leads for TYMS regulation.
AB  - OBJECTIVE: Methotrexate (MTX) is the drug of first choice for the treatment of
      rheumatoid arthritis (RA), but is effective only in around 60% of the patients.
      Identification of genetic markers to predict response is essential for effective
      treatment within a critical window period of 6 months after diagnosis, but have
      been hitherto elusive. In this study, we used genome-wide genotype data to
      identify the potential risk variants associated with MTX (poor)response in a
      north Indian RA cohort. MATERIALS AND METHODS: Genome-wide genotyping data for a
      total of 457 RA patients [297 good (DAS28-3<=3.2) and 160 poor (DAS28-3>=5.1)
      responders] on MTX monotherapy were tested for association using an additive
      model. Support vector machine and genome-wide pathway analysis were used to
      identify additional risk variants and pathways. All risk loci were imputed to
      fine-map the association signals and identify causal variant(s) of
      therapeutic/diagnostic relevance. RESULTS: Seven novel suggestive loci from
      genome-wide (P<=5*10(-5)) and three from support vector machine analysis were
      associated with MTX (poor)response. The associations of published candidate genes
      namely DHFR (P=0.014), FPGS (P=0.035), and TYMS (P=0.005) and purine and
      nucleotide metabolism pathways were reconfirmed. Imputation, followed by
      bioinformatic analysis indicated possible interaction between two reversely
      oriented overlapping genes namely ENOSF1 and TYMS at the post-transcriptional
      level. CONCLUSION: In this first ever genome-wide analysis on MTX treatment
      response in RA patients, 10 new risk loci were identified. These preliminary
      findings warrant replication in independent studies. Further, TYMS expression at
      the post-transcriptional level seems to be probably regulated through an
      antisense-RNA involving the 6-bp ins/del marker in the overlapping segment at
      3'UTR of TYMS-ENOSF1, a finding with impending pharmacogenetic applications.

PMID- 24583628
TI  - Risk stratification of organ-specific GVHD can be improved by single-nucleotide
      polymorphism-based risk models.
AB  - We aimed to develop a risk model, based on single-nucleotide polymorphism (SNP)
      markers associated with an increased risk of organ-specific GVHD in 394
      transplant pairs. A total of 259 SNPs were genotyped in 53 genes and evaluated
      for their associated risk of organ-specific GVHD. Risk models were generated
      using both clinical factors and genetic SNP markers. Patients were stratified by
      quartiles according to their risk scores and then categorized into three groups
      (low, intermediate and high risk) according to this model. We compared the risk
      of overall and organ-specific GVHD amongst these groups. Several SNP markers in
      the cytokine-, apoptosis-, TGF-beta- and PDGF-mediated pathways were identified
      as correlative markers of acute and chronic GVHD. Each organ-specific GVHD shared
      some common biologic pathway such as cytokine, TGF-beta- or PDGF-mediated
      pathways. However, we also identified different SNP markers that correlated with
      increased risk of organ-specific GVHD (for example, FCGR2A SNP for oral GVHD, and
      FAS and TGFB1 SNP for lung GVHD). The incorporation of genetic risk factors into
      the clinical factors risk model improved stratification power for organ-specific
      GVHD. The SNP-based approach was suggested to improve risk stratification of
      organ-specific GVHD. 

PMID- 24583631
TI  - Attenuation of antigenic immunogenicity by kynurenine, a novel suppressive
      adjuvant.
AB  - A novel therapeutic strategy is required for autoimmune diseases characterized by
      the production of autoantibody, because current clinical strategies have
      limitations. Vaccination against autoimmune diseases is a feasible strategy
      because vaccines induce immune response memory and the antigen specificity.
      However, no suitable adjuvant is available to direct the immune response toward
      tolerance or suppression. In the current study, we evaluated whether kynurenine
      (Kyn) could serve as a novel suppressive adjuvant to decrease the humoral immune
      responses against hepatitis A virus (HAV) in the ICR mouse model in vivo and
      lipopolysaccharide (LPS) in B cells in vitro. The underlying mechanisms of Kyn
      mediated suppression of LPS-induced IgM responses were explored. The results
      showed that Kyn significantly decreased HAV immunogenicity when co-administered
      with HAV, and that Kyn (100 MUM/1000 MUM) impaired IgM generation compared with
      that induced by LPS alone. We also demonstrated that microRNA30b (miR30b) played
      a critical role in the process of Kyn-mediated suppression of IgM responses
      induced by LPS, and that Bach2, a transcriptional repressor of B cell terminal
      differentiation, was a novel target of miR30b. These findings suggest that Kyn
      can serve as a novel and effective suppressive adjuvant for vaccines. 

PMID- 24583632
TI  - Attrition and adherence in a WEB-Based Distress Management Program for
      Implantable Cardioverter defibrillator Patients (WEBCARE): randomized controlled
      trial.
AB  - BACKGROUND: WEB-Based Distress Management Program for Implantable CARdioverter
      defibrillator Patients (WEBCARE) is a Web-based randomized controlled trial,
      designed to improve psychological well-being in patients with an implantable
      cardioverter defibrillator (ICD). As in other Web-based trials, we encountered
      problems with attrition and adherence. OBJECTIVE: In the current study, we focus
      on the patient characteristics, reasons, and motivation of (1) completers, (2)
      those who quit the intervention, and (3) those who quit the intervention and the
      study in the treatment arm of WEBCARE. METHODS: Consecutive first-time ICD
      patients from six Dutch referral hospitals were approached for participation.
      After signing consent and filling in baseline measures, patients were randomized
      to either the WEBCARE group or the Usual Care group. RESULTS: The treatment arm
      of WEBCARE contained 146 patients. Of these 146, 34 (23.3%) completed the
      treatment, 88 (60.3%) dropped out of treatment but completed follow-up, and 24
      (16.4%) dropped out of treatment and study. Results show no systematic
      differences in baseline demographic, clinical, or psychological characteristics
      between groups. A gradual increase in dropout was observed with 83.5% (122/146)
      completing the first lesson, while only 23.3% (34/146) eventually completed the
      whole treatment. Reasons most often given by patients for dropout were technical
      problems with the computer, time constraints, feeling fine, and not needing
      additional support. CONCLUSIONS: Current findings underline the importance of
      focusing on adherence and dropout, as this remains a significant problem in
      behavioral Web-based trials. Examining possibilities to address barriers
      indicated by patients might enhance treatment engagement and improve patient
      outcomes. TRIAL REGISTRATION: Clinicaltrials.gov: NCT00895700;
      http://www.clinicaltrials.gov/ct2/show/NCT00895700 (Archived by WebCite at
      http://www.webcitation.org/6NCop6Htz).

PMID- 24583633
TI  - Basic cell penetrating peptides induce plasma membrane positive curvature, lipid
      domain separation and protein redistribution.
AB  - Basic cell penetrating peptides are tools for molecular cellular internalization
      of nonmembrane permeable molecules. Their uptake mechanisms involve energy
      dependent and energy-independent pathways such as endocytosis, direct
      translocation or physical endocytosis. These mechanisms are ruled by both, the
      peptides physicochemical properties and structure and by the membrane lipids
      characteristics and organization. Herein we used plasma membrane spheres and
      membrane models to study the membrane perturbations induced by three arginine
      rich cell penetrating peptides. Nona-arginine (R9) and the amphipathic peptide
      RWRRWWRRW (RW9) induced positive membrane curvature in the form of buds and
      membrane tubes. Membranous tubes underwent rolling resulting in formation of
      multilamellar membrane particles at the surface of the plasma membrane spheres.
      The amphipathic peptides RW9 and RRWRRWWRRWWRRWRR (RW16) provoked lipid and
      membrane associated protein domain separation as well as changes in membrane
      fluidity and cholesterol redistribution. These data suggest that membrane domains
      separation and the formation of multilamellar membranous particles would be
      involved in arginine-rich cell penetrating peptides internalization. 

PMID- 24583634
TI  - A question for women's health: chemicals in feminine hygiene products and
      personal lubricants.

PMID- 24583635
TI  - Assessment of radiological hazard of commercial granites from Extremadura
      (Spain).
AB  - The term "commercial granite" comprises different natural stones with different
      mineralogical components. In Extremadura, western Spain, "commercial granites"
      can be classified in three types: granite s.s. (sensus stricti), granodiorite,
      and diorite. The content of naturally occurring radionuclides depended of the
      mineralogy. Thus, the (40)K content increased as the relative content of alkaline
      feldspar increased but decreased as the plagioclase content increased. The
      radioactive content decreased in the following order: granite s.s. > granodiorite
      > diorite. In this work, the radiological hazard of these granites as building
      material was analyzed in terms of external irradiation and radon exposure.
      External irradiation was estimated based on the "I" index, ranged between 0.073
      and 1.36. Therefore, these granites can be use as superficial building materials
      with no restriction. Radon exposure was estimated using the surface exhalation
      rates in polished granites. The exhalation rate in granites depends of their
      superficial finishes (different roughness). For distinct mechanical finishes of
      granite (polish, diamond sawed, bush-hammered and flamed), the surface exhalation
      rate increased with the roughness of the finishes. Thermal finish presented the
      highest exhalation rate, because the high temperatures applied to the granite may
      increase the number of fissures within it. The exhalation rates in polished
      granites varied from 0.013 to 10.4 Bq m(-2) h(-1). 

PMID- 24583637
TI  - Bcl-6 controlled TFH polarization and memory: the known unknowns.
AB  - Upon antigenic activation in vivo, naive CD4 T cells can differentiate into one
      of several helper (Th) subsets under the control of lineage-specifying
      transcription factors to tailor immune responses against different types of
      pathogens. Follicular T-helper (TFH) cells are a recently defined subset that is
      controlled by Bcl-6 and specializes in promoting B cell-mediated humoral
      immunity. TFH cells exhibit unique spatiotemporal and functional features, but it
      is not settled as to how Bcl-6 promotes the TFH development, how TFH cells relate
      to other Th subsets, and how TFH cells relate to memory. Here we review recent
      advances and crucial gaps in our understanding of Bcl-6-controlled TFH
      development and function. 

PMID- 24583636
TI  - Vaccine immunity against fungal infections.

PMID- 24583638
TI  - Oncogene-induced reactive oxygen species fuel hyperproliferation and DNA damage
      response activation.
AB  - Oncogene-induced reactive oxygen species (ROS) have been proposed to be signaling
      molecules that mediate proliferative cues. However, ROS may also cause DNA damage
      and proliferative arrest. How these apparently opposite roles can be reconciled,
      especially in the context of oncogene-induced cellular senescence, which is
      associated both with aberrant mitogenic signaling and DNA damage response (DDR)
      mediated arrest, is unclear. Here, we show that ROS are indeed mitogenic
      signaling molecules that fuel oncogene-driven aberrant cell proliferation.
      However, by their very same ability to mediate cell hyperproliferation, ROS
      eventually cause DDR activation. We also show that oncogenic Ras-induced ROS are
      produced in a Rac1 and NADPH oxidase (Nox4)-dependent manner. In addition, we
      show that Ras-induced ROS can be detected and modulated in a living transparent
      animal: the zebrafish. Finally, in cancer we show that Nox4 is increased in both
      human tumors and a mouse model of pancreatic cancer and specific Nox4 small
      molecule inhibitors act synergistically with existing chemotherapic agents. 

PMID- 24583639
TI  - Low-dose radiation exposure induces a HIF-1-mediated adaptive and protective
      metabolic response.
AB  - Because of insufficient understanding of the molecular effects of low levels of
      radiation exposure, there is a great uncertainty regarding its health risks. We
      report here that treatment of normal human cells with low-dose radiation induces
      a metabolic shift from oxidative phosphorylation to aerobic glycolysis resulting
      in increased radiation resistance. This metabolic change is highlighted by
      upregulation of genes encoding glucose transporters and enzymes of glycolysis and
      the oxidative pentose phosphate pathway, concomitant with downregulation of
      mitochondrial genes, with corresponding changes in metabolic flux through these
      pathways. Mechanistically, the metabolic reprogramming depends on HIF1alpha,
      which is induced specifically by low-dose irradiation linking the metabolic
      pathway with cellular radiation dose response. Increased glucose flux and
      radiation resistance from low-dose irradiation are also observed systemically in
      mice. This highly sensitive metabolic response to low-dose radiation has
      important implications in understanding and assessing the health risks of
      radiation exposure. 

PMID- 24583640
TI  - G0/G1 switch gene 2 has a critical role in adipocyte differentiation.
AB  - Mouse 3T3-L1 preadipocytes differentiate into adipocytes when treated with 3
      isobutyl-1-methylxanthine, dexamethasone, and insulin. Although mechanisms of
      adipogenesis, including transcriptional cascades, are understood, it is still
      unclear how clonally expanded cells eventually enter the terminal differentiation
      program. From gene expression profile studies, we identified G0/G1 switch gene 2
      (G0s2) as a novel regulator of adipogenesis. The gene was found to be expressed
      at a higher level in white and brown adipose tissues, and it was induced in 3T3
      L1 cells by hormonal treatment. Importantly, G0s2 expression was closely
      associated with the transition from mitotic clonal expansion to terminal
      differentiation. Knockdown of G0s2 expression with siRNA inhibited adipocyte
      differentiation, whereas constitutive overexpression of G0s2 accelerated
      differentiation of preadipocytes to mature adipocytes. Expression of G0s2 was
      found to be regulated by peroxisome proliferator-activated receptor gamma
      (PPARgamma), which is a well-known regulator of adipocyte differentiation.
      Absence of either PPARgamma or G0s2 expression resulted in apoptotic pathway
      activation before terminal differentiation. To determine whether G0s2 has a role
      in vivo, G0s2-knockout mice were generated. The knockout mice were normal in
      appearance, but they had less adipose mass than wild-type littermates. Mouse
      embryonic fibroblast cells from G0s2-deficient mice exhibited impaired
      adipogenesis and contained unusually small intracellular lipid droplets,
      suggesting that G0s2 has a role in lipid droplet formation. Our studies
      demonstrate that G0s2 has an important role in adipogenesis and accumulation of
      triacylglycerol. 

PMID- 24583641
TI  - Endogenous c-Myc is essential for p53-induced apoptosis in response to DNA damage
      in vivo.
AB  - Recent studies have suggested that C-MYC may be an excellent therapeutic cancer
      target and a number of new agents targeting C-MYC are in preclinical development.
      Given most therapeutic regimes would combine C-MYC inhibition with genotoxic
      damage, it is important to assess the importance of C-MYC function for DNA damage
      signalling in vivo. In this study, we have conditionally deleted the c-Myc gene
      in the adult murine intestine and investigated the apoptotic response of
      intestinal enterocytes to DNA damage. Remarkably, c-Myc deletion completely
      abrogated the immediate wave of apoptosis following both ionizing irradiation and
      cisplatin treatment, recapitulating the phenotype of p53 deficiency in the
      intestine. Consistent with this, c-Myc-deficient intestinal enterocytes did not
      upregulate p53. Mechanistically, this was linked to an upregulation of the E3
      Ubiquitin ligase Mdm2, which targets p53 for degradation in c-Myc-deficient
      intestinal enterocytes. Further, low level overexpression of c-Myc, which does
      not impact on basal levels of apoptosis, elicited sustained apoptosis in response
      to DNA damage, suggesting c-Myc activity acts as a crucial cell survival rheostat
      following DNA damage. We also identify the importance of MYC during DNA damage
      induced apoptosis in several other tissues, including the thymus and spleen,
      using systemic deletion of c-Myc throughout the adult mouse. Together, we have
      elucidated for the first time in vivo an essential role for endogenous c-Myc in
      signalling DNA damage-induced apoptosis through the control of the p53 tumour
      suppressor protein. 

PMID- 24583644
TI  - Micro-CT and histologic analyses of bone surrounding immediately loaded miniscrew
      implants: comparing compression and tension loading.
AB  - This study investigated the effect of immediate force on bone adaptations
      surrounding miniscrew implants. Ten miniscrew implants were placed on the
      mandibles in three beagle dogs. Five pairs of miniscrew implants were immediately
      loaded with 150 g of continuous force using nickel-titanium coil springs for 8
      weeks. The values of bone mineral density (BMD), bone mineral content (BMC), and
      bone volume (BV) of cortical and trabecular bone for compression loading and
      tension loading were obtained by uCT analysis. The percentages of bone-to-implant
      contact (BIC) in the compression and tension regions for cortical and trabecular
      bone were obtained by histologic analysis. The BMD values for the compression
      region of cortical bone were significantly higher compared to the tension region.
      The BIC values in cortical and trabecular bone at tension and compression regions
      were similar. In conclusion, immediate loading does not inhibit osseointegration
      of miniscrew implants but may stimulate bone mineralization. 

PMID- 24583642
TI  - Notch1 regulates progenitor cell proliferation and differentiation during mouse
      yolk sac hematopoiesis.
AB  - Loss-of-function studies have demonstrated the essential role of Notch in
      definitive embryonic mouse hematopoiesis. We report here the consequences of
      Notch gain-of-function in mouse embryo hematopoiesis, achieved by constitutive
      expression of Notch1 intracellular domain (N1ICD) in angiopoietin receptor
      tyrosine kinase receptor-2 (Tie2)-derived enhanced green fluorescence protein
      (EGFP(+)) hematovascular progenitors. At E9.5, N1ICD expression led to the
      absence of the dorsal aorta hematopoietic clusters and of definitive
      hematopoiesis. The EGFP(+) transient multipotent progenitors, purified from E9.5
      to 10.5 Tie2-Cre;N1ICD yolk sac (YS) cells, had strongly reduced hematopoietic
      potential, whereas they had increased numbers of hemogenic endothelial cells.
      Late erythroid cell differentiation stages and mature myeloid cells (Gr1(+),
      MPO(+)) were also strongly decreased. In contrast, EGFP(+) erythro-myeloid
      progenitors, immature and intermediate differentiation stages of YS erythroid and
      myeloid cell lineages, were expanded. Tie2-Cre;N1ICD YS had reduced numbers of
      CD41(++) megakaryocytes, and these produced reduced below-normal numbers of
      immature colonies in vitro and their terminal differentiation was blocked. Cells
      from Tie2-Cre;N1ICD YS had a higher proliferation rate and lower apoptosis than
      wild-type (WT) YS cells. Quantitative gene expression analysis of FACS-purified
      EGFP(+) YS progenitors revealed upregulation of Notch1-related genes and
      alterations in genes involved in hematopoietic differentiation. These results
      represent the first in vivo evidence of a role for Notch signaling in YS
      transient definitive hematopoiesis. Our results show that constitutive Notch1
      activation in Tie2(+) cells hampers YS hematopoiesis of E9.5 embryos and
      demonstrate that Notch signaling regulates this process by balancing the
      proliferation and differentiation dynamics of lineage-restricted intermediate
      progenitors. 

PMID- 24583645
TI  - Microbiologically influenced corrosion of orthodontic metallic appliances.
AB  - Biocorrosion (microbiologically influenced corrosion; MIC) occur in aquatic
      habitats varying in nutrient content, temperature, stress and pH. The oral
      environment of organisms, including humans, should be one of the most hospitable
      for MIC. Corrosion of metallic appliances in the oral region is one cause of
      metal allergy in patients. In this study, an inductively coupled plasma-optical
      emission spectrometer revealed elution of Fe, Cr and Ni from stainless steel
      (SUS) appliances incubated with oral bacteria. Three-dimensional laser confocal
      microscopy also revealed that oral bacterial culture promoted increased surface
      roughness and corrosion pits in SUS appliances. The pH of the supernatant was
      lowered after co-culture of appliances and oral bacteria in any combinations, but
      not reached at the level of depassivation pH of their metallic materials. This
      study showed that Streptococcus mutans and Streptococcus sanguinis which easily
      created biofilm on the surfaces of teeth and appliances, did corrode orthodontic
      SUS appliances. 

PMID- 24583643
TI  - RIP1 maintains DNA integrity and cell proliferation by regulating PGC-1alpha
      mediated mitochondrial oxidative phosphorylation and glycolysis.
AB  - Aerobic glycolysis or the Warburg effect contributes to cancer cell
      proliferation; however, how this glucose metabolism pathway is precisely
      regulated remains elusive. Here we show that receptor-interacting protein 1
      (RIP1), a cell death and survival signaling factor, regulates mitochondrial
      oxidative phosphorylation and aerobic glycolysis. Loss of RIP1 in lung cancer
      cells suppressed peroxisome proliferator-activated receptor gamma coactivator
      1alpha (PGC-1alpha) expression, impairing mitochondrial oxidative phosphorylation
      and accelerating glycolysis, resulting in spontaneous DNA damage and p53-mediated
      cell proliferation inhibition. Thus, although aerobic glycolysis within a certain
      range favors cancer cell proliferation, excessive glycolysis causes cytostasis.
      Our data suggest that maintenance of glycolysis by RIP1 is pivotal to cancer cell
      energy homeostasis and DNA integrity and may be exploited for use in anticancer
      therapy. 

PMID- 24583646
TI  - Bone response of TGF-beta2 immobilized titanium in a rat model.
AB  - The present study aimed to immobilize TGF-beta2 onto titanium implants by using a
      tresyl chloride-activation technique and to evaluate the bone response of TGF
      beta2 immobilized titanium (TGF-beta2/Ti) implants in a rat femur defect model.
      XPS and FT-IR measurements identified the presence of TGF-beta2 on titanium.
      Atomic force microscopy showed globular images of immobilized TGF-beta2. The
      contact angle of TGF-beta2/Ti against water significantly decreased compared with
      untreated titanium (Ti). There was no change of surface roughness after
      immobilization of TGF-beta2. Ti and TGF-beta2/Ti implants were inserted into rat
      femur defects. TGF-beta2/Ti showed more bone formation by calcein labeling and
      histological observation. The measurements of bone to implant contact (BIC) and
      bone mass (BM) around the implants revealed that BIC and BM of TGF-beta2/Ti
      implants were significantly higher than those of Ti at 4 weeks after the
      implantation. In conclusion, TGF-beta2/Ti implant effectively enhances bone
      regeneration around implants. 

PMID- 24583647
TI  - The surface characterization and bioactivity of NANOZR in vitro.
AB  - The purpose of this study was to evaluate the surface characterization and
      bioactivity of ceria-stabilized zirconia/alumina nanocomposite (NANOZR) in
      comparison to yttria-stabilized zirconia (3Y-TZP) and pure titanium (CpTi). Three
      dimension surface morphology, surface wettability, bovine serum albumin
      adsorption rate, cell morphology, cell proliferation and ALP activity of three
      tested materials were measured. There were no significant differences in surface
      roughness, contact angle among the three materials. The ALP expression of NANOZR
      was higher than CpTi and 3Y-TZP at 14 and 21 days although bovine serum albumin
      adsorption rate, cell morphology; and cell proliferation was not different among
      the three materials. These results suggest that the three test materials
      basically had similar surface characterization and bioactivity. Within the
      limitations of this study, our results show that the three test materials were
      biologically similar bio-inert materials. 

PMID- 24583648
TI  - Optimizing the design of bio-inspired functionally graded material (FGM) layer in
      all-ceramic dental restorations.
AB  - Due to elastic modulus mismatch between the different layers in all-ceramic
      dental restorations, high tensile stress concentrates at the interface between
      the ceramic core and cement. In natural tooth structure, stress concentration is
      reduced by the functionally graded structure of dentin-enamel junction (DEJ)
      which interconnects enamel and dentin. Inspired by DEJ, the aim of this study was
      to explore the optimum design of a bio-inspired functionally graded material
      (FGM) layer in all-ceramic dental restorations to achieve excellent stress
      reduction and distribution. Three-dimensional finite element model of a multi
      layer structure was developed, which comprised bilayered ceramic, bio-inspired
      FGM layer, cement, and dentin. Finite element method and first-order optimization
      technique were used to realize the optimal bio-inspired FGM layer design. The bio
      inspired FGM layer significantly reduced stress concentration at the interface
      between the crown and cement, and stresses were evenly distributed in FGM layer.
      With the optimal design, an elastic modulus distribution similar to that in DEJ
      occurred in the FGM layer. 

PMID- 24583649
TI  - A novel technique for preparing dental CAD/CAM composite resin blocks using the
      filler press and monomer infiltration method.
AB  - The authors have developed a new technique for preparing dental CAD/CAM composite
      resin blocks (CRBs): the filler press and monomer infiltration (FPMI) method. In
      this method, surface-treated filler is molded into a green body in which the
      filler particles are compressed to form an agglomeration. The green body is then
      infiltrated with a monomer mixture before being polymerized. It is possible to
      produce CRBs using this method through which densely packed nanofiller is
      uniformly dispersed. The greater the pressure of the filler molding, the more
      filler in the CRB, resulting at high pressure in a very dense CRB. A CRB obtained
      by applying 170 MPa of pressure contained up to 70 wt% of nano-silica filler and
      had a flexural strength of 200 MPa, as well. It is anticipated that CRBs obtained
      using the FPMI method will be useful as a dental CAD/CAM material for the
      fabrication of permanent crown restorations. 

PMID- 24583650
TI  - Aqueous synthesis of Cu-doped ZnCdS/ZnS core/shell nanocrystals with a new and
      highly reactive sulfur source.
AB  - A new sulfur precursor with a highly reactive chemical nature was prepared with S
      powder and NaBH4 at the high temperature of 180  degrees C in a closed autoclave
      and made it possible to carry out the synthesis of high quality metal sulfide
      nanocrystals (NCs) with diverse composition and structure. Using this new sulfur
      source, we demonstrated aqueous synthesis of colloidal Cu-doped ZnCdS NCs (d
      dots) with pure, color-tunable photoluminescence (PL) in a wide spectral range
      (from 517 to 650 nm) based on the 'co-nucleation doping' strategy. The influences
      of the various experimental variables, including Cd/Zn ratio, Cu-doping
      concentration, pH value and amount of mercaptopropionic acid (MPA), on the
      optical properties of Cu-doped ZnCdS NCs were systematically investigated.
      Furthermore, highly efficient and stable dopant emission from Cu:ZnCdS/ZnS
      core/shell d-dots with PL quantum yield as high as 40% was achieved by the
      deposition of a ZnS shell around the bare Cu:ZnCdS cores; this is the highest
      reported to date for aqueous doped NCs. The optical properties and structure of
      the d-dots were characterized by UV-vis absorption spectra, PL spectra, x-ray
      photoelectron spectroscopy, powder x-ray diffraction, and transmission electron
      microscopy. The experimental results indicated that this facile synthesis route
      would provide a versatile approach for the preparation of other water-soluble
      sulfide NCs.

PMID- 24583651
TI  - Toll-like receptor-5 agonist Entolimod broadens the therapeutic window of 5
      fluorouracil by reducing its toxicity to normal tissues in mice.
AB  - Myelosuppression and gastrointestinal damage are common side effects of cancer
      treatment limiting efficacy of DNA-damaging chemotherapeutic drugs. The Toll-like
      receptor 5 (TLR5) agonist Entolimod has demonstrated efficacy in mitigating
      damage to hematopoietic and gastrointestinal tissues caused by radiation. Here,
      using 5-Fluorouracil (5-FU) treated mice as a model of chemotherapy-induced side
      effects, we demonstrated significant reduction in the severity of 5-FU-induced
      morbidity and increased survival accompanied by the improved integrity of
      intestinal tissue and stimulated the restoration of hematopoiesis. Entolimod
      stimulated IL-6 production was essential for Entolimod's ability to rescue mice
      from death caused by doses of 5-FU associated with hematopoietic failure. In
      contrast, IL-6 induction was not necessary for protection and restoration of drug
      damaged gastrointestinal tissue by Entolimod. In a syngeneic mouse CT26 colon
      adenocarcinoma model, Entolimod reduced the systemic toxicity of 5-FU, but did
      not reduce its antitumor efficacy indicating that the protective effect of
      Entolimod was selective for normal, non-tumor, tissues. These results suggest
      that Entolimod has clinical potential to broaden the therapeutic window of
      genotoxic anticancer drugs by reducing their associated hematopoietic and
      gastrointestinal toxicities. 

PMID- 24583652
TI  - Polychlorinated biphenyls and hexachlorocyclohexanes in sediments and fish
      species from the Napoleon Gulf of Lake Victoria, Uganda.
AB  - Polychlorinated biphenyls (PCBs) and hexachlorocyclohexanes (HCHs) were analyzed
      in surface sediments (<30 cm depth) and two fish species: Nile perch (Lates
      niloticus) and Nile tilapia (Oreochromis niloticus). The samples were collected
      from the Napoleon Gulf on the northern shore of Lake Victoria. The analysis was
      done using a gas chromatograph (GC) coupled to a high resolution mass
      spectrometer for PCBs and a GC equipped with an electron capture detector for
      HCHs. Total (Sigma) PCBs in the muscles of fish varied widely with mean values
      ranging from 41 to 670 pg g(-1) lipid weight (lw). The PCB levels in L. niloticus
      were significantly greater than those in O. niloticus. The large variability
      observed in the data was attributed to differences in feeding habits and trophic
      levels. While O. niloticus is a filter-eating fish species feeding mainly on
      phytoplankton and zooplankton, L. niloticus have predatory feeding behaviors and
      prefer a diet of live fish and, therefore, are more prone to bio-accumulate
      contaminants. The mean PCB concentrations in the sediments varied from 362 to 848
      pg g(-1) dry weight. Variations in PCB levels were observed from one study site
      to another, this was attributed to the nature and particle size of the sediments.
      HCH isomers were detected in fish at mean concentrations of up to 45,900 pg g(-1)
      lw. The PCB and HCH concentrations were lower than those from previous studies
      elsewhere in literature and were below the maximum residue limits set by the
      European Commission and FAO/WHO Codex Alimentarius Commission, implying that the
      fish was fit for human consumption.

PMID- 24583653
TI  - Default mode network alterations during language task performance in children
      with benign epilepsy with centrotemporal spikes (BECTS).
AB  - Benign epilepsy with centrotemporal spikes (BECTS) is the most common idiopathic
      epileptic disorder in children. Besides reported cognitive deficits, functional
      alterations mostly in the reorganization of language areas have also been
      described. In several publications, it has been reported that activation of the
      default mode network (DMN) can be reduced or altered in different
      neuropsychiatric and neurological disorders in adults. Whether this also holds
      true for children with epilepsy has so far not been clarified. To determine the
      functional activation of the DMN in children with BECTS, 20 patients and 16
      healthy controls were examined using functional magnetic resonance imaging
      (fMRI), while a sentence generation task and a reading task were applied in a
      block design manner. To study the default mode network and the functional
      alterations between groups, an independent component analysis (ICA) was computed
      and further analyzed using SPM5. Compared with controls, children with BECTS
      showed not only significantly less activation of the DMN during the rest
      condition but also less deactivation during cognitive effort. This was most
      apparent in the precuneus, a key region of the DMN, while subjects were
      generating sentences. From these findings, we hypothesize that children with
      BECTS show a functional deficit that is reflected by alterations in the DMN. 

PMID- 24583654
TI  - Stressors and resources of caregivers of patients with incurable progressive
      illness in sub-Saharan Africa.
AB  - Family caregivers are central to palliative care in sub-Saharan Africa. Yet
      although supporting caregivers requires a comprehensive understanding of
      caregiver burden, there has been little research into this topic in Africa. Using
      the Stress Process Model to investigate the burden experienced by caregivers in
      South Africa and Uganda, we interviewed 37 caregivers and analyzed the data
      thematically. Caregivers' primary stressors related to day-to-day patient care
      and emotional support; secondary stressors included financial hardship, family
      responsibilities, and social isolation. Caregivers' social, relational,
      spiritual, and psychological resources mediated the effects of these stressors.
      Strengthening one resource strengthened others, but the failure of one resource
      hindered other resources, exacerbating burden. In providing caregiver support,
      policymakers and service providers should focus on enhancing caregivers'
      resources as well as alleviating their stressors. 

PMID- 24583655
TI  - Letter from the editor.

PMID- 24583657
TI  - Letter from the President of PSNCB.

PMID- 24583656
TI  - President's Message.

PMID- 24583658
TI  - The life after weight loss program: a paradigm for plastic surgery care after
      massive weight loss.
AB  - Obesity has become a nationwide problem. In every state, at least 1 in 5
      individuals is obese. Because of the obesity epidemic and the comorbidities
      associated with obesity, many people turn to bariatric surgery as a treatment
      option. The most popular bariatric procedures are Roux-en-Y gastric bypass,
      sleeve gastrectomy, and gastric banding. With the success of these procedures,
      patients experience massive weight loss in a short period of time. Their weight
      loss can be from 50 lb to more than 100 lb. Because of this massive weight loss,
      patients are left with loose hanging skin. Body contouring in plastic surgery has
      increased in demand, following the popularity in bariatric procedures. In 2002,
      the Life After Weight Loss clinical program was established at the University of
      Pittsburgh, by Dr. J. Peter Rubin, Chair of the Department of Plastic Surgery,
      UPMC, and Director of the Life After Weight Loss Program. 

PMID- 24583660
TI  - Preparing the skin for surgery.
AB  - In 1867, Joseph Lister wrote this account of how to prepare the skin for surgery:
      "A solution of one part crystallised carbolic acid in four parts of boiled
      linseed oil having been prepared, a piece of rag from four to six inches square
      is dipped in the oily mixture, and laid upon the skin where the incision is to be
      made." Nearly 150 years later, the science of preoperative skin preparation has
      grown more sophisticated, but continues to be the cornerstone of evidence-based
      practices to prevent surgical site infections (SSIs) and promote positive
      surgical outcomes. 

PMID- 24583661
TI  - The "nuts & bolts" of becoming an aesthetic provider: part 2-building your
      aesthetic practice.
AB  - Part 2 of this three-part series of articles on becoming an aesthetic provider
      centers on the steps necessary to build an aesthetic practice. We will discuss
      the legal (e.g., licensure, scope of practice, malpractice, and documentation)
      and the business aspects (e.g., "your brand," staff development, networking,
      marketing, and revenue possibilities) of building a successful aesthetic
      practice. On the basis of years of experience, "pearls and pitfalls" will be
      discussed so novice, intermediate, and advanced aesthetic providers can minimize
      mistakes and maximize their success in this exciting and growing profession. 

PMID- 24583662
TI  - Make a statement - your brand is your business.

PMID- 24583663
TI  - Pediatric plastic surgery: four-dimensional medicine.
AB  - Pediatric plastic surgery is a very rewarding and challenging field. Many of our
      patients are managed longitudinally, often into adulthood, and deal with complex
      surgical problems. The role of an experienced nurse in outpatient plastic surgery
      is critical to managing these complex patients. The role of the pediatric plastic
      surgery nurse also includes coordination of care and detailed knowledge of
      patients and families to help direct the formation of individualized treatment
      plans. This role, though challenging, also allows nurses to form strong bonds
      with their patients and families and serve as a source of advocacy, support, and
      information. 

PMID- 24583664
TI  - Customizing compounded topical anesthetic preparations.

PMID- 24583665
TI  - "Sign here": nursing value and the process of informed consent.
AB  - Protecting patient autonomy is a key nursing role. The Code of Ethics (American
      Nurses Association, 2010), contextualizes the nurse's call to advocacy within the
      doctrine of informed consent. This article offers a primer on the legal, ethical,
      and practical aspects of procedural informed consent and examines the value of
      nursing's role within the process. The theory of nursing's value is sound, but
      the literature lacks data. Higher levels of evidence are necessary to make sound
      decisions about best practice for the process of informed consent. As such, this
      article concludes that adding nursing research to the current discourse should
      prove most valuable to patients, providers, and the nursing profession as a
      whole.

PMID- 24583667
TI  - Knotless tissue control devices: an asset in plastic surgery.

PMID- 24583666
TI  - Utility of high-frequency ultrasound: moving beyond the surface to detect changes
      in skin integrity.
AB  - Ultrasound imaging is a versatile modality frequently used in clinical medicine,
      most likely due to its low cost, low risk to patients, and the ability to provide
      images in real time. Ultrasound used typically in clinical settings has
      frequencies between 2 and 12 MHz. Lower frequencies produce greater resolution
      but are limited in depth penetration; higher frequencies produce greater
      resolution, but depth of penetration is limited. High-frequency ultrasound (HFUS)
      shows promise for detection of certain changes in the skin and this has
      implications for early detection of changes associated with pressure ulcer
      formation and wound healing. The purpose of this article was to provide an
      overview of where HFUS has been used with the skin and provide some discussion on
      its utility with detecting skin changes related to pressure. 

PMID- 24583668
TI  - Over-expression of hypoxia-inducible factor-1 alpha in vitro protects the cardiac
      fibroblasts from hypoxia-induced apoptosis.
AB  - OBJECTIVES: A great number of studies indicate that cardiac fibroblasts are
      essential for maintaining the structure and function of heart. Hypoxia-inducible
      factor-1 alpha (HIF-1alpha) is a central transcriptional regulator of hypoxic
      response. The present study examined whether over-expression of HIF-1alpha could
      prevent hypoxia-induced injury in neonatal rat cardiac fibroblasts and, if so,
      its possible molecular targets. METHODS: Western blotting was used to detect
      protein level. MTT, electron microscopy, TUNEL staining and confocal microscopy
      were used to identify cell viability, cell apoptosis and intracellular calcium
      ([Ca]i) in cardiac fibroblasts, respectively. RESULTS: When cardiac fibroblasts
      were exposed to hypoxia, HIF-1alpha protein in nuclei was transiently accumulated
      at 1 h, and then gradually degraded within 24 h of hypoxia exposure. Over
      expression of HIF-1alpha enhanced nucleus expression of HIF-1alpha in cardiac
      fibroblasts, and significantly abolished the decrease of cell viability and cell
      apoptosis caused by 24-h hypoxia. Accordingly, hypoxia-induced Bax up-regulation,
      Bcl-2 down-regulation, caspase-3 activation and overload of [Ca]i in cardiac
      fibroblasts were reversed by HIF-1alpha over-expression, but were promoted by 30
      MUmol/l SC205346, a specific HIF-1alpha blocker. CONCLUSIONS: Our results
      indicate that HIF-1alpha may act as a protective factor in the apoptotic process
      of cardiac fibroblasts and represent a potential therapeutic target for heart
      remodeling after hypoxia injury.

PMID- 24583669
TI  - Immunologic response and myocardial free wall rupture in infective endocarditis.

PMID- 24583672
TI  - Silica nanoparticles induce autophagy and autophagic cell death in HepG2 cells
      triggered by reactive oxygen species.
AB  - Silica nanoparticles (SNPs) are becoming favorable carriers for drug delivery or
      gene therapy, and in turn, the toxic effect of SNPs on biological systems is
      gaining attention. Currently, autophagy is recognized as an emerging toxicity
      mechanism triggered by nanomaterials, yet there have been scarcely research about
      the mechanisms of autophagy and autophagic cell death associated with SNPs. In
      this study, we verified the activation of SNPs-induced autophagy via the MDC
      staining and LC3-I/LC3-II conversion, resulted in a dose-dependent manner. The
      typically morphological characteristics (autophagosomes and autolysosomes) of the
      autophagy process were observed in TEM ultrastructural analysis. In addition, the
      autophagic cell death was evaluated by cellular co-staining assay. And the
      underlying mechanisms of autophagy and autophagic cell death were performed using
      the intracellular ROS detection, autophagy inhibitor and ROS scavenger. Results
      showed that the elevated ROS level was in line with the increasing of autophagy
      activation, while both the 3-MA and NAC inhibitors effectively suppressed the
      autophagy and cell death induced by SNPs. In summary, our findings demonstrated
      that the SNPs-induced autophagy and autophagic cell death were triggered by the
      ROS generation in HepG2 cells, suggesting that exposure to SNPs could be a
      potential hazardous factor for maintaining cellular homeostasis.

PMID- 24583673
TI  - Selective removal of cesium from aqueous solutions with nickel (II)
      hexacyanoferrate (III) functionalized agricultural residue-walnut shell.
AB  - A novel nickel (II) hexacyanoferrate (III) functionalized agricultural residue
      walnut shell (Ni(II)HCF(III)-WS) was developed to selectively remove cesium ion
      (Cs(+)) from aqueous solutions. This paper showed the first integral study on
      Cs(+) removal behavior and waste reduction analysis by using biomass adsorption
      material. The results indicated that the removal process was rapid and reached
      saturation within 2h. As a special characteristic of Ni(II)HCF(III)-WS, acidic
      condition was preferred for Cs(+) removal, which was useful for extending the
      application scope of the prepared biomass material in treating acidic radioactive
      liquid waste. The newly developed Ni(II)HCF(III)-WS could selectively remove
      Cs(+) though the coexisting ions (Na(+) and K(+) in this study) exhibited
      negative effects. In addition, approximately 99.8% (in volume) of the liquid
      waste was reduced by using Ni(II)HCF(III)-WS and furthermore 91.9% (in volume) of
      the spent biomass material (Cs-Ni(II)HCF(III)-WS) was reduced after incineration
      (at 500 degrees C for 2h). Due to its relatively high distribution coefficient
      and significant volume reduction, Ni(II)HCF(III)-WS is expected to be a promising
      material for Cs(+) removal in practice.

PMID- 24583670
TI  - Laboratory adverse events and discontinuation of therapy according to CD4(+) cell
      count at the start of antiretroviral therapy.
AB  - OBJECTIVE: Few data describe antiretroviral treatment (ART)-related adverse
      events when treatment is initiated at CD4(+) cell counts more than 350 cells/MUl.
      We compared rates of laboratory-defined adverse events (LDAEs) according to
      CD4(+) cell count at ART initiation. DESIGN: Analysis of on-going cohort study.
      METHODS: ART-naive persons initiating ART from 2000 to 2010 were included. Chi
      square, analysis of variance (ANOVA) and Kruskal-Wallis tests compared
      characteristics among those starting ART with a CD4(+) cell count of 350 or less,
      351-499 and at least 500 cells/MUl. Time-updated Poisson regression compared
      rates of LDAE in the three CD4(+) cell strata. Cox proportional hazard models
      compared risk of ART discontinuation. RESULTS: Nine thousand, four hundred and
      six individuals were included: median age 37 years, 61% white, 80% men, median
      viral load 4.8 log copies/ml. Four hundred and forty-seven (4.9%) and 1099
      (11.7%) started ART with a CD4(+) cell count at least 500 and 351-499 cells/MUl,
      respectively. One thousand, two hundred and eighty-three (13.6%) patients
      experienced at least one LDAE. The rate of LDAE did not differ between those
      starting ART with a CD4(+) cell count 351-499 and less than 350 cells/MUl
      [relative rate 0.90, 95% confidence interval (CI) 0.74-1.09)], but an increased
      risk of ART discontinuation was observed (hazard ratio 1.58, 95% CI 1.10-2.27).
      Those starting ART at CD4(+) cell count at least 500 cells/MUl had an increased
      rate of LDAE (relative rate 1.44, 95% CI 1.13-1.82) but were not more likely to
      discontinue ART (hazard ratio 1.15, 95% CI 0.64-2.09). CONCLUSION: This study
      demonstrates the need to consider ART-related toxicities when initiating therapy
      at CD4(+) cell counts at least 500 cells/MUl. Whilst evidence from randomized
      controlled trials is awaited, the timing of ART initiation in terms of benefits
      and risks of ART remains an important question.

PMID- 24583674
TI  - Updated exposure-response relationship between road traffic noise and coronary
      heart diseases: a meta-analysis.
AB  - A meta-analysis of 14 studies (17 individual effect estimates) on the association
      between road traffic noise and coronary heart diseases was carried out. A
      significant pooled estimate of the relative risk of 1.08 (95% confidence
      interval: 1.04, 1.13) per increase of the weighted day-night noise level L DN of
      10 dB (A) was found within the range of approximately 52-77 dB (A) (5 dB-category
      midpoints). The results gave no statistically significant indication of
      heterogeneity between the results of individual studies. However, stratified
      analyses showed that the treatment of gender in the studies, the lowest age of
      study subjects and the lowest cut-off of noise levels had an impact on the effect
      estimates of different studies. The result of the meta-analysis complies
      quantitatively with the result of a recent meta-analysis on the association
      between road traffic noise and hypertension. Road traffic noise is a significant
      risk factor for cardiovascular diseases. 

PMID- 24583671
TI  - Genotypic resistance profiles of HIV-2-treated patients in West Africa.
AB  - OBJECTIVE: To assess the virological response, genotypic resistance profiles, and
      antiretroviral plasma concentrations in HIV-2 antiretroviral-treated
      (antiretroviral therapy, ART) patients in Cote d'Ivoire. METHODS: A cross
      sectional survey was conducted among HIV-2 patients receiving ART. Plasma HIV-2
      viral load was performed using the Agence Nationale de Recherche sur le SIDA et
      les hepatites virales (ANRS) assay. Protease and reverse transcriptase sequencing
      was performed using in-house methods and antiretroviral plasma concentrations
      were assessed using ultra performance liquid chromatography combined with tandem
      mass spectrometry. RESULTS: One hundred and forty-five HIV-2-treated patients
      were enrolled with a median CD4 cell count of 360 cells/MUl (interquartile range,
      IQR = 215-528). Median duration of ART was 4 years (IQR = 2-7) and 74% of
      patients displayed viral load less than 50 copies/ml. Median plasma HIV-2 RNA
      among patients with viral load more than 50 copies/ml was 3016 copies/ml (IQR =
      436-5156). Most patients (84%) received a lopinavir/ritonavir-based regimen. HIV
      2 resistance mutations to nucleoside reverse transcriptase inhibitors and
      protease inhibitors were detected in 21 of 25 (84%) and 20 of 29 (69%) samples,
      respectively. The most prevalent nucleoside reverse transcriptase inhibitor
      resistance mutations were M184I/V (90%), Q151M (24%), and S215F/Y (24%). The most
      prevalent protease inhibitor resistance mutations were V47A (60%) and I54M (30%).
      Median CD4 cell counts were 434 cells/MUl (292-573) and 204 cells/MUl (122-281)
      in patients with viral load less than 50 copies/ml and those exhibiting
      virological failure (P < 0.0001), respectively. The proportions of patients with
      adequate antiretroviral plasma concentrations were 81 and 93% in patients
      displaying virological failure and in those with viral load less than 50
      copies/ml, respectively (P = 0.046), suggesting good treatment adherence.
      CONCLUSION: We observed adequate drug plasma concentrations and virological
      suppression in a high proportion of HIV-2-infected patients. However, in cases of
      virological failure, the limited HIV-2 therapeutic arsenal and cross-resistance
      dramatically reduced treatment options.

PMID- 24583675
TI  - The assessment and evaluation of low-frequency noise near the region of
      infrasound.
AB  - The main aim of this paper is to present recent knowledge about the assessment
      and evaluation of low-frequency sounds (noise) and infrasound, close to the
      threshold of hearing, and identify their potential effect on human health and
      annoyance. Low-frequency noise generated by air flowing over a moving car with an
      open window was chosen as a typical scenario which can be subjectively assessed
      by people traveling by automobile. The principle of noise generated within the
      interior of the car and its effects on the comfort of the driver and passengers
      are analyzed at different velocities. An open window of a car at high velocity
      behaves as a source of specifically strong tonal low-frequency noise which is
      generally perceived as annoying. The interior noise generated by an open window
      of a passenger car was measured under different conditions: Driving on a highway
      and driving on a typical roadway. First, an octave-band analysis was used to
      assess the noise level and its impact on the driver's comfort. Second, a fast
      Fourier transform (FFT) analysis and one-third octave-band analysis were used for
      the detection of tonal low-frequency noise. Comparison between two different car
      makers was also done. Finally, the paper suggests some possibilities for
      scientifically assessing and evaluating low-frequency sounds in general, and some
      recommendations are introduced for scientific discussion, since sounds with
      strong low-frequency content (but not only strong) engender greater annoyance
      than is predicted by an A-weighted sound pressure level. 

PMID- 24583676
TI  - Possible effects of rosuvastatin on noise-induced oxidative stress in rat brain.
AB  - The problem of noise has recently gained more attention as it has become an
      integral part of our daily lives. However, its influence has yet to be fully
      elucidated. Other than being an unpleasant stimulus, noise may cause health
      disorders through annoyance and stress, including oxidative stress. Rosuvastatin,
      a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, may possess
      antioxidant properties. Based on rat models, our project investigates the effect
      of rosuvastatin on noise-induced oxidative stress in the brain tissue. Thirty-two
      male Wistar albino rats were used. The rats were divided into four groups: Noise
      exposure plus rosuvastatin usage, only noise exposure, only rosuvastatin usage,
      and control. After the data had been collected, oxidant and antioxidant
      parameters were analyzed in the cerebral cortex, brain stem, and cerebellum.
      Results indicated that superoxide dismutase values were significantly decreased
      in the cerebral cortex, while malondialdehyde values in the brainstem and
      cerebellum were significantly increased in the group with only noise exposure.
      Superoxide dismutase values in the brainstem were significantly increased, but
      nitric oxide values in the cerebellum and brainstem and malondialdehyde values in
      the cerebellum and cerebral cortex were significantly decreased in the group
      where only rosuvastatin was used. During noise exposure, the use of rosuvastatin
      caused significantly increased superoxide dismutase values in the cerebral cortex
      and brainstem, but significantly reduced malondialdehyde values in the brain
      stem. Consequently, our data show that brain tissue was affected by oxidative
      stress due to continued exposure to noise. This noise-induced stress decreases
      with rosuvastatin therapy. 

PMID- 24583677
TI  - Prevalence and characteristics of tinnitus after leisure noise exposure in young
      adults.
AB  - The main goal of this study was to assess the prevalence and characteristics of
      tinnitus among students after exposure to leisure noise. In addition, the effects
      of tinnitus on otoacoustic emissions (OAEs) in participants suffering from
      chronic tinnitus were evaluated. The study consisted of two parts. First, a
      questionnaire regarding leisure noise exposure and tinnitus was completed.
      Second, the hearing status of the subjects suffering from chronic tinnitus was
      evaluated and compared with a matched control group (CG). Furthermore, the
      psychoacoustical characteristics of their tinnitus in the chronic tinnitus group
      (TG) were established. The questionnaire was answered by 151 respondents. Seven
      persons suffering from chronic tinnitus were examined further in the second part
      of the study. Transient tinnitus was observed in 73.5% of the respondents after
      leisure noise exposure and 6.6% experienced chronic tinnitus. Transient and
      chronic tinnitus had similar characteristics, as established by the
      questionnaire. The amplitude of transient evoked otoacoustic emissions and
      distortion product otoacoustic emissions was reduced and the amount of efferent
      suppression was smaller in the TG as compared with the CG. Tinnitus induced by
      leisure noise is observed frequently in young adults. The characteristics of
      tinnitus cannot predict whether it will have a transient or rather a chronic
      nature. In subjects suffering from tinnitus, subclinical damage that cannot be
      detected by audiometry can be demonstrated by measuring OAEs. These findings
      underpin the importance of educating youth about the risks of noise exposure
      during leisure activities. 

PMID- 24583678
TI  - Please silence your cell phone: Your ringtone captures other people's attention.
AB  - Ringtones are designed to draw attention away from on-going activities. In the
      present study, it was investigated whether the disruptive effects of a ringing
      cell phone on short-term memory are inevitable or become smaller as a function of
      exposure and whether (self-) relevance plays a role. Participants performed a
      serial recall task either in silence or while task-irrelevant ringtones were
      presented. Performance was worse when a ringing phone had to be ignored, but
      gradually recovered compared with the quiet control condition with repeated
      presentation of the distractor sound. Whether the participant's own ringtone was
      played or that of a yoked-control partner did not affect performance and
      habituation rate. The results offer insight into auditory distraction by highly
      attention-demanding distractors and recovery therefrom. Implications for work
      environments and other applied settings are discussed. 

PMID- 24583679
TI  - Evaluation of the noise exposure of symphonic orchestra musicians.
AB  - For musicians, the impact of noise exposure is not yet fully characterized. Some
      inconsistencies can be found in the methodology used to evaluate noise exposure.
      This study aims to analyze the noise exposure of musicians in a symphonic
      orchestra to understand their risk for hearing loss, applying the methodology
      proposed by ISO 9612:2009. Noise levels were monitored among musicians during the
      rehearsal of eight different repertoires. Test subjects were selected according
      to their instrument and position in the orchestra. Participants wore noise
      dosimeters throughout the rehearsals. A sound meter was used to analyze the
      exposure of the conductor. The results showed that musicians are exposed to high
      noise levels that can damage hearing. Brass, woodwind and percussion and timpani
      musicians were exposed to noise levels in excess of the upper exposure action
      level of 85 dB (A), while the other instrumental groups had a lower exposure
      action level of 80 dB (A). Percussion musicians were exposed to high peak noise
      levels of 135 dB (C). Sound levels varied by instrument, repertoire and position.
      Octave frequency analyses showed differences among musicians. This study suggests
      that musicians are at risk for hearing loss. There is a need for more effective
      guidelines applicable to all countries, which should define standardized
      procedures for determining musician noise exposure and should allow exposure
      level normalization to the year, including different repertoires. 

PMID- 24583680
TI  - Noise sensitivity and diminished health: testing moderators and mediators of the
      relationship.
AB  - The concept of noise sensitivity emerged in public health and psychoacoustic
      research to help explain individual differences in reactions to noise. Noise
      sensitivity has been associated with health problems, but the mechanisms
      underlying this relationship have yet to be fully examined. Participants (n =
      1102) were residents of Auckland, New Zealand, who completed questionnaires and
      returned them through the post. Models of noise sensitivity and health were
      tested in the analyses using bootstrapping methods to examine indirect effects.
      Results indicated that gender and noise exposure were not significant moderators
      in the model. Perceived stress and sleep problems were significant mediators of
      the relationship between noise sensitivity and subjective health complaints, even
      after controlling for the influence of neuroticism. However, the relationship
      between noise sensitivity and mental health complaints (anxiety and depression)
      was accounted for by the variance explained by neuroticism. Overall, this study
      provides considerable understanding of the relationship between noise sensitivity
      and health problems and identifies areas for further research in the field. 

PMID- 24583681
TI  - Auditory stimulation with music influences the geometric indices of heart rate
      variability in response to the postural change maneuver.
AB  - It is poor in the literature the behavior of the geometric indices of heart rate
      variability (HRV) during the musical auditory stimulation. The objective is to
      investigate the acute effects of classic musical auditory stimulation on the
      geometric indexes of HRV in women in response to the postural change maneuver
      (PCM). We evaluated 11 healthy women between 18 and 25 years old. We analyzed the
      following indices: Triangular index, Triangular interpolation of RR intervals and
      Poincariota plot (standard deviation of the instantaneous variability of the beat
      to beat heart rate [SD1], standard deviation of long-term continuous RR interval
      variability and Ratio between the short - and long-term variations of RR
      intervals [SD1/SD2] ratio). HRV was recorded at seated rest for 10 min. The women
      quickly stood up from a seated position in up to 3 s and remained standing still
      for 15 min. HRV was recorded at the following periods: Rest, 0-5 min, 5-10 min
      and 10-15 min during standing. In the second protocol, the subject was exposed to
      auditory musical stimulation (Pachelbel-Canon in D) for 10 min at seated position
      before standing position. Shapiro-Wilk to verify normality of data and ANOVA for
      repeated measures followed by the Bonferroni test for parametric variables and
      Friedman's followed by the Dunn's posttest for non-parametric distributions. In
      the first protocol, all indices were reduced at 10-15 min after the volunteers
      stood up. In the protocol musical auditory stimulation, the SD1 index was reduced
      at 5-10 min after the volunteers stood up compared with the music period. The
      SD1/SD2 ratio was decreased at control and music period compared with 5-10 min
      after the volunteers stood up. Musical auditory stimulation attenuates the
      cardiac autonomic responses to the PCM. 

PMID- 24583682
TI  - Development of a traffic noise prediction model for an urban environment.
AB  - The objective of this study is to develop a traffic noise model under diverse
      traffic conditions in metropolitan cities. The model has been developed to
      calculate equivalent traffic noise based on four input variables i.e. equivalent
      traffic flow (Q e ), equivalent vehicle speed (S e ) and distance (d) and honking
      (h). The traffic data is collected and statistically analyzed in three different
      cases for 15-min during morning and evening rush hours. Case I represents
      congested traffic where equivalent vehicle speed is <30 km/h while case II
      represents free-flowing traffic where equivalent vehicle speed is >30 km/h and
      case III represents calm traffic where no honking is recorded. The noise model
      showed better results than earlier developed noise model for Indian traffic
      conditions. A comparative assessment between present and earlier developed noise
      model has also been presented in the study. The model is validated with measured
      noise levels and the correlation coefficients between measured and predicted
      noise levels were found to be 0.75, 0.83 and 0.86 for case I, II and III
      respectively. The noise model performs reasonably well under different traffic
      conditions and could be implemented for traffic noise prediction at other region
      as well. 

PMID- 24583683
TI  - Healthy weight regulation and eating disorder prevention in high school students:
      a universal and targeted Web-based intervention.
AB  - BACKGROUND: Given the rising rates of obesity in children and adolescents,
      developing evidence-based weight loss or weight maintenance interventions that
      can be widely disseminated, well implemented, and are highly scalable is a public
      health necessity. Such interventions should ensure that adolescents establish
      healthy weight regulation practices while also reducing eating disorder risk.
      OBJECTIVE: This study describes an online program, StayingFit, which has two
      tracks for universal and targeted delivery and was designed to enhance healthy
      living skills, encourage healthy weight regulation, and improve weight/shape
      concerns among high school adolescents. METHODS: Ninth grade students in two high
      schools in the San Francisco Bay area and in St Louis were invited to
      participate. Students who were overweight (body mass index [BMI] >85th
      percentile) were offered the weight management track of StayingFit; students who
      were normal weight were offered the healthy habits track. The 12-session program
      included a monitored discussion group and interactive self-monitoring logs.
      Measures completed pre- and post-intervention included self-report height and
      weight, used to calculate BMI percentile for age and sex and standardized BMI
      (zBMI), Youth Risk Behavior Survey (YRBS) nutrition data, the Weight Concerns
      Scale, and the Center for Epidemiological Studies Depression Scale. RESULTS: A
      total of 336 students provided informed consent and were included in the
      analyses. The racial breakdown of the sample was as follows: 46.7% (157/336)
      multiracial/other, 31.0% (104/336) Caucasian, 16.7% (56/336) African American,
      and 5.7% (19/336) did not specify; 43.5% (146/336) of students identified as
      Hispanic/Latino. BMI percentile and zBMI significantly decreased among students
      in the weight management track. BMI percentile and zBMI did not significantly
      change among students in the healthy habits track, demonstrating that these
      students maintained their weight. Weight/shape concerns significantly decreased
      among participants in both tracks who had elevated weight/shape concerns at
      baseline. Fruit and vegetable consumption increased for both tracks. Physical
      activity increased among participants in the weight management track, while soda
      consumption and television time decreased. CONCLUSIONS: Results suggest that an
      Internet-based, universally delivered, targeted intervention may support healthy
      weight regulation, improve weight/shape concerns among participants with eating
      disorders risk, and increase physical activity in high school students. Tailored
      content and interactive features to encourage behavior change may lead to
      sustainable improvements in adolescent health.

PMID- 24583684
TI  - In-situ fluorescent immunomagnetic multiplex detection of foodborne pathogens in
      very low numbers.
AB  - Consumption of foods contaminated with pathogenic bacteria is a major public
      health concern. Foods contain microorganisms, the overwhelming majority of which
      are nonpathogenic, some are responsible for food spoilage, and some cause serious
      illness leading to death or a variety of diseases in humans. The key challenge in
      food safety is to rapidly screen foods to determine the presence of pathogens so
      that appropriate intervention protocols can be pursued. A simple fluorometric
      immunological method in combination with a magnetic concentration step was
      developed for rapid detection of target bacteria with high sensitivity and
      specificity in less than 2h without enumeration. The method constitutes
      performing an in-situ immunoassay on a magnetic bead through the formation of a
      sandwich complex of the target bacteria and the probe (detection antibody
      denatured BSA labelled with fluorophores) followed by the release of fluorophores
      by means of enzymatic digestion with proteinase K. The limit of detection (LOD)
      was <5 CFU/mL of the tested pathogens (Escherichia coli O157:H7, Salmonella
      typhimurium, and Listeria monocytogenes) in buffer. When the pathogens were
      inoculated in foods (spinach, chicken, and milk), the LOD was under 5 CFU/mL for
      E. coli O157:H7, S. typhimurium and L. monocytogenes. Furthermore, the method was
      highly specific in detecting the target pathogens in a multiplex format. The
      developed in-situ fluorescent immunomagnetic sensor approach offers distinct
      advantages because it is rapid, highly sensitive, and easy to use and could
      therefore be potentially used as a pathogen screening tool.

PMID- 24583685
TI  - Polyoxometalate@magnetic graphene as versatile immobilization matrix of
      Ru(bpy)3(2+) for sensitive magneto-controlled electrochemiluminescence sensor and
      its application in biosensing.
AB  - We demonstrated here the exploration of polyoxometalate (POM) coated magnetic
      Fe3O4/reduced graphene oxide (POM@mrGO) composite as the versatile immobilization
      matrix for the electrochemiluminescence (ECL) agent Ru(bpy)3(2+). The effective
      modification of Ru(bpy)3(2+)/POM@mrGO hybrid simply involved using magnetic
      electrode showed 10-fold ECL intensity increase than that observed for
      Ru(bpy)3(2+)/Nafion@mrGO to the same concentration of nicotinamide adenine
      dinucleotide (NADH), which is largely due to POM's good electrocatalytic activity
      towards NADH oxidation. These findings allowed the stable and ultrasensitive ECL
      detection of NADH as low as 0.1 nM. The good stability and high sensitivity of
      the magneto-controlled ECL sensor enabled us to explore the feasibility of
      applying the sensing platform to fabricating the ECL biosensors in which the NADH
      was produced from the dehydrogenase-based enzymatic reaction in the presence of
      NAD(+) cofactor. With L-lactate dehydrogenase as a model, a L-lactate biosensor
      was successfully constructed where we showed that the ECL intensity of the
      biosensor increased with the increasing L-lactate concentration. Excellent
      performance of the presented biosensor has been achieved including a wide linear
      range extended from 5.0*10(-9) M to 5.0*10(-4) M and an extremely low detection
      limit of 0.4 nM. Such sensing strategy combines enzymatic selectivity with simple
      sensor preparation can be used as a new and biocompatible platform for
      dehydrogenase-based ECL biosensing.

PMID- 24583686
TI  - A nanowire-based label-free immunosensor: direct incorporation of a PSA antibody
      in electropolymerized polypyrrole.
AB  - We have suggested a novel method for the preparation of a label-free
      electrochemical immunosensor for the detection of prostate-specific antigen (PSA)
      as target marker for prostate cancer. Direct incorporation of PSA antibody (anti
      PSA) into polypyrrole (Ppy) electropolymerized on a three-dimensional Au nanowire
      array has resulted in enhanced molecular interactions, ultimately leading to
      improved sensing performance. The electrochemical performance of the nanowire
      based immunosensor array were characterized by (1) differential pulse voltammetry
      (DPV) to evaluate the specific recognition of PSA, (2) impedance and cyclic
      voltammetry to observe surface resistance and electroactivity, and (3) scanning
      electron microscopy (SEM) to demonstrate the three-dimensional architecture. The
      vertically-aligned geometric organization of Ppy provides a novel platform to
      improve the anti-PSA loading capacity. Overall, enhanced electrochemical
      performance of the proposed immunosensor has been demonstrated by its linear
      response over PSA concentrations ranging from 10 fg mL(-1) to 10 ng mL(-1) and a
      detection limit of 0.3 fg mL(-1), indicating that the strategy proposed here has
      great potential for clinical applications.

PMID- 24583687
TI  - High sensitive mesoporous TiO2-coated love wave device for heavy metal detection.
AB  - This work deals with the design of a highly sensitive whole cell-based biosensor
      for heavy metal detection in liquid medium. The biosensor is constituted of a
      Love wave sensor coated with a polyelectrolyte multilayer (PEM). Escherichia coli
      bacteria are used as bioreceptors as their viscoelastic properties are influenced
      by toxic heavy metals. The acoustic sensor is constituted of a quartz substrate
      with interdigitated transducers and a SiO2 guiding layer. However, SiO2 shows
      some degradation when used in a saline medium. Mesoporous TiO2 presents good
      mechanical and chemical stability and offers a high active surface area. Then,
      the addition of a thin titania layer dip-coated onto the acoustic path of the
      sensor is proposed to overcome the silica degradation and to improve the mass
      effect sensitivity of the acoustic device. PEM and bacteria deposition, and heavy
      metal influence, are real time monitored through the resonance frequency
      variations of the acoustic device. The first polyelectrolyte layer is inserted
      through the titania mesoporosity, favouring rigid link of the PEM on the sensor
      and improving the device sensitivity. Also, the mesoporosity of surface increases
      the specific surface area which can be occupied and favors the formation of
      homogeneous PEM. It was found a frequency shift near -20+/-1 kHz for bacteria
      immobilization with titania film instead of -7+/-3 kHz with bare silica surface.
      The sensitivity is highlighted towards cadmium detection. Moreover, in this
      paper, particular attention is given to the immobilization of bacteria and to
      biosensor lifetime. Atomic Force Microscopy characterizations of the biosurface
      have been done for several weeks. They showed significant morphological
      differences depending on the bacterial life time. We noticed that the lifetime of
      the biosensor is longer in the case of using a mesoporous TiO2 layer.

PMID- 24583688
TI  - Molecular recognition of proteolytic activity in metastatic cancer cells using
      fluorogenic gold nanoprobes.
AB  - We describe the development of biomarker-sensitive nanoprobes based on
      nanoparticle surface energy transfer (NSET) effect that enabling recognition of
      the expression of membrane type-1 matrix metalloproteinase (MT1-MMP) anchored on
      invasive cancer cells and its proteolytic activity simultaneously. First of all,
      we confirmed invasiveness of cancer cell lines (HT1080 and MCF7) via migration
      and invasion assay. We also prepared gold nanoparticle (GNP) acts as a quencher
      for fluorescein isothiocyanate (FITC). This FITC is conjugated in end-terminal of
      activatable fluorogenic peptide (ActFP). The ActFP attach to surface of GNP (GNP
      ActFP) for a targeting moiety and proteolytic activity ligand toward MT1-MMP. The
      GNP-ActFP can generate fluorescence signal when ActFP is cleaved by proteolytic
      activity after targeting toward MT1-MMP. In order to study specificity for MT1
      MMP, GNP-ActFP is treated to HT1080 and MCF7 cells, and then, we determine the in
      vitro targeting potential and fluorogenic activity of GNP-ActFP for MT1-MMP via
      fluorescence multi-reader. We also confirmed fluorogenic activity of GNP-ActFP
      via confocal microscopic imaging, and finally, endocytosis of GNP-ActFP is
      observed via cellular transmission electron microscopic imaging. 

PMID- 24583689
TI  - Detection of copper ions in drinking water using the competitive adsorption of
      proteins.
AB  - Heavy metal ions, i.e., Cu(2+), are harmful to the environment and our health. In
      order to detect them, and circumvent or alleviate the weaknesses of existing
      detecting technologies, we contrive a unique Surface Plasmon Resonance (SPR)
      biosensor combined with competitive adsorption of proteins, termed the Vroman
      effect. This approach adopts native proteins (albumin) as bio-receptors that
      interact with Cu(2+) to be denatured. Denaturation disrupts the conformation of
      albumin so that it weakens its affinity to adsorb on the sensing surface. Through
      the competitive adsorption between the denatured albumins and the native ones,
      the displacement occurs adjacent to the sensing surface, and this process is real
      time monitored by SPR, a surface-sensitive label-free biosensor. The affinities
      of native albumin is significantly higher than that of denatured albumin,
      demonstrated by measured KD of native and denatured albumin to gold surafce,
      5.8+/-0.2*10(-5) M and 5.4+/-0.1*10(-4) M, respectively. Using our biosensor,
      Cu(2+) with concentration down to 0.1mg/L is detected in PBS, tap water,
      deionized water, and bottled water. The SPR biosensor is characterized for 5
      different heavy metal ions, Cu(2+), Fe(3+), Mn(2+), Pb(2+), and Hg(2+), most
      common heavy metal ions found in tap water. At the maximum contaminant level
      (MCL) suggested by the United States Environmental Protection Agency (EPA), the
      SPR biosensor produces 13.5+/-0.4, 1.5+/-0.4, 0, 0, and 0 mDeg, respectively,
      suggesting the biosensor may be used to detect Cu(2+) in tap water samples.

PMID- 24583690
TI  - A polyadenosine-coralyne complex as a novel fluorescent probe for the sensitive
      and selective detection of heparin in plasma.
AB  - This study presents the development of a simple, label-free, sensitive, and
      selective detection system for heparin based on the use of a complex of 20-repeat
      adenosine (A20) and coralyne. Coralyne emits relatively weak fluorescence in an
      aqueous solution. In the presence of A20, coralyne molecules complexed with A20
      through A2-coralyne-A2 coordination. An increase in the fluorescence of coralyne
      was observed because coralyne remained separate from water in the hydrophobic
      environment of the folded A20. The presence of heparin and the formation of the
      coralyne-heparin complex caused coralyne to be removed from the A20-corlayne
      complex. Because heparin promoted coralyne dimerization, the fluorescence of
      coralyne decreased as a function of the concentration of added heparin. This
      detection method is effective because the electrostatic attraction between
      heparin and coralyne is substantially stronger than the coordination between A20
      and coralyne in a 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES)
      buffer at pH 7.0. Under optimal conditions (5 MUM coralyne, 1 MUM poly A20, and
      10mM HEPES), this probe exhibited high selectivity (>90-fold) toward heparin over
      hyaluronic acid and chondroitin sulfate. The probe's detection limit for heparin
      was determined to be 4 nM (75 ng/mL) at a signal-to-noise ratio of 3. This study
      validates the practicality of using the A20-corlayne complex to determine the
      concentration of heparin in plasma.

PMID- 24583691
TI  - Development of an indirect competitive assay-based aptasensor for highly
      sensitive detection of tetracycline residue in honey.
AB  - Tetracycline (TC) is widely used for prevention and control of animal diseases
      for its broad spectrum antimicrobial activity and low cost, but its abuse can
      seriously affect human health and may result in trade loss. Thus there is an
      imperative need to develop high-performing analytical technique for TC detection.
      In this study, we developed a biosensor based on an indirect competitive enzyme
      linked aptamer assay (ic-ELAA). A 76mer single-stranded DNA (ssDNA) aptamer,
      selected by Systematic Evolution of Ligands by Exponential Enrichment (SELEX),
      was applied for the recognition and detection of TC in honey. The limit of
      detection was 9.6*10(-3) ng/mL with a linear working range from 0.01 to 100 ng/mL
      toward TC in honey, and a mean recovery rate of 93.23% in TC-spiked honey was
      obtained. This aptasensor can be applied to detect TC residue in food with high
      sensitivity and simplicity, and it is prospective to develop useful ELAA Kits for
      TC determination in food.

PMID- 24583692
TI  - Label-free electrochemical immunosensor based on gold-silicon carbide
      nanocomposites for sensitive detection of human chorionic gonadotrophin.
AB  - Uniform and highly dispersed gold-silicon carbide (Au@SiC) nanocomposites were
      prepared via simple way and used for fabrication of label-free electrochemical
      immunosensor for sensitive detection of human chorionic gonadotrophin (hCG).
      Using Au@SiC as electrode material and using ferricyanide as mediator, the
      proposed immunosensor provides a simple and economic method with higher
      sensitivity and a wider concentration range for detection of hCG. Under the
      optimal condition, the approach provided a good linear response range from 0.1 to
      5 IU/L and 5 to 1000 IU/L with a low detection limit of 0.042 IU/L. The
      immunosensor showed good selectivity, acceptable stability and reproducibility.
      Satisfactory results were obtained for determination of hCG in human serum
      samples. The proposed method provides a promising platform of clinical
      immunoassay for other biomolecules. In addition, the bio-functionalization of SiC
      combined with other nanomaterials will provide promising approach for
      electrochemical sensing and biosensing platform.

PMID- 24583693
TI  - Direct biosensor detection of botulinum neurotoxin endopeptidase activity in sera
      from patients with type A botulism.
AB  - Botulinum neurotoxin A (BoNT/A) has intrinsic endoprotease activity specific for
      SNAP-25, a key protein for presynaptic neurotransmitter release. The inactivation
      of SNAP-25 by BoNT/A underlies botulism, a rare but potentially fatal disease.
      There is a crucial need for a rapid and sensitive in vitro serological test for
      BoNT/A to replace the current in vivo mouse bioassay. Cleavage of SNAP-25 by
      BoNT/A generates neo-epitopes which can be detected by binding of a monoclonal
      antibody (mAb10F12) and thus measured by surface plasmon resonance (SPR). We have
      explored two SPR assay formats, with either mAb10F12 or His6-SNAP-25 coupled to
      the biosensor chip. When BoNT/A was incubated with SNAP-25 in solution and the
      reaction products were captured on a mAb-coated chip, a sensitivity of 5 fM
      (0.1LD50/ml serum) was obtained. However, this configuration required prior
      immunoprecipitation of BoNT/A. A sensitivity of 0.5 fM in 10% serum (0.1 LD50/ml
      serum) was attained when SNAP-25 was coupled directly to the chip, followed by
      sequential injection of BoNT/A samples and mAb10F12 into the flow system to
      achieve on-chip cleavage and detection, respectively. This latter format detected
      BoNT/A endoprotease activity in 50-100 ul serum samples from all patients (11/11)
      with type A botulism within 5h. No false positives occurred in sera from healthy
      subjects or patients with other neurological diseases. The automated chip-based
      procedure has excellent specificity and sensitivity, with significant advantages
      over the mouse bioassay in terms of rapidity, required sample volume and animal
      ethics.

PMID- 24583694
TI  - Microarray based on autodisplayed Ro proteins for medical diagnosis of systemic
      lupus erythematosus (SLE).
AB  - A microarray-based immunoassay for the detection of autoantibodies against Ro
      protein was developed using Escherichia coli with autodisplayed Ro proteins
      (Ro(+)-E. coli). Patient serum usually contains various antibodies against the
      outer membrane components of E. coli as well as autoantibodies against the Ro
      protein. Therefore, the conventional immunoassay based on Ro(+)-E. coli requires
      both wild type E. coli (blank test) and Ro(+)-E. coli, and both strains of E.
      coli must be prepared in situ for each individual test serum. In this study, we
      tested the feasibility of using several types of animal sera as a replacement for
      individual human sera. An immunoassay without the blank test was developed using
      Ro(+)-E. coli by (1) blocking with rabbit serum, and (2) cleaving the Fc region
      from antibodies using papain. Modified E. coli with autodisplayed Ro protein was
      immobilized to a surface-modified microplate and the applicability of the
      immunoassay without the blank test was demonstrated using sera from patients with
      systemic lupus erythematosus (SLE). Using this approach, a microarray-based
      fluorescence immunoassay with immobilized Ro(+)-E. coli was able to detect anti
      Ro autoantibodies in SLE patient sera with high specificity and selectivity and
      improved efficiency. 

PMID- 24583695
TI  - A novel label-free amperometric immunosensor for carcinoembryonic antigen based
      on Ag nanoparticle decorated infinite coordination polymer fibres.
AB  - In this article, for the first time, a novel, high-yield and template-free method
      for the synthesis of Ag nanoparticle decorated thionine/infinite coordination
      polymer (AgNP/THI/ICP) fibres is proposed. The thionine can be adsorbed to the
      AgNP/THI/ICP fibres by pi-conjugation and act as the redox probe. The
      AgNP/THI/ICP fibres not only favor the immobilization of antibody but also
      facilitate the electron transfer. It is found that the AgNP/THI/ICP fibres can be
      designed to act as a sensitive label-free electrochemical immunosensor for
      carcinoembryonic antigen (CEA) determination. Under the optimized conditions, the
      linear range of the proposed immunosensor is estimated to be from 50 fg/mL to 100
      ng/mL and the detection limit is estimated to be 0.5 fg/mL at a signal-to-noise
      ratio of 3, respectively. The prepared immunosensor for detection of CEA shows
      high sensitivity, reproducibility and stability. Our study demonstrates that the
      proposed immunosensor has also been used to determine CEA successfully in diluted
      blood samples.

PMID- 24583696
TI  - Age-related mandible abrasion in the groundhopper Tetrix tenuicornis (Tetrigidae,
      Orthoptera).
AB  - A study was conducted to determine whether the mandibles of the detrito
      /bryophagous groundhopper Tetrix tenuicornis are subject to mechanical wear as a
      result of feeding, as is the case for grasshoppers that feed on silica-rich
      grasses. Abrasion was evaluated by measuring the length and width of the 3rd
      incisor and length of the 4th incisor in adults of different ages collected under
      natural conditions during one season. Although T. tenuicornis and other
      groundhoppers avoid feeding on grasses, we found that mandible abrasion increased
      with T. tenuicornis age. Age-related abrasion of the incisors of left and right
      mandibles was statistically significant in both sexes but the degree of abrasion
      was greater for females than males, apparently reflecting differences in the
      frequency and magnitude of feeding. Degree of abrasion also differed between
      right and left mandibles, probably because of differences in how each mandible is
      used during food processing. Abrasion of cuticular mandible structures may reduce
      the effectiveness of food processing late in the season.

PMID- 24583698
TI  - The role of surface and deep-level defects on the emission of tin oxide quantum
      dots.
AB  - This paper reports on the role of surface and deep-level defects on the blue
      emission of tin oxide quantum dots (SnO2 QDs) synthesized by the solution
      combustion method at different combustion temperatures. X-ray diffraction studies
      showed the formation of a single rutile SnO2 phase with a tetragonal lattice
      structure. High resolution transmission electron microscopy studies revealed an
      increase in the average dot size from 2.2 to 3.6 nm with an increase of the
      combustion temperature from 350 to 550  degrees C. A decrease in the band gap
      value from 3.37 to 2.76 eV was observed with the increase in dot size due to the
      quantum confinement effect. The photoluminescence emission was measured for
      excitation at 325 nm and it showed a broad blue emission band for all the
      combustion temperatures studied. This was due to the creation of various oxygen
      and tin vacancies/defects as confirmed by x-ray photoelectron spectroscopy data.
      The origin of the blue emission in the SnO2 QDs is discussed with the help of an
      energy band diagram.

PMID- 24583697
TI  - Ras and autophagy in cancer development and therapy.
AB  - Autophagy, a process of self-degradation and turnover of cellular components,
      plays a complex role in cancer. Evidence exists to show that autophagy may
      support tumor growth and cell survival, whereas it can also contribute to tumor
      suppression and have anti-survival characteristics in different cellular systems.
      Numerous studies have described the effects of various oncogenes and tumor
      suppressors on autophagy. The small GTPase Ras is an oncogene involved in the
      regulation of various cell-signaling pathways, and is mutated in 33% of human
      cancers. In the present review, we discuss the interplay between Ras and
      autophagy in relation to oncogenesis. It appears that Ras can upregulate or
      downregulate autophagy through several signaling pathways. In turn, autophagy can
      affect the tumorigenicity driven by Ras, resulting in either tumor progression or
      repression, depending on the cellular context. Furthermore, Ras inhibitors were
      shown to induce autophagy in several cancer cell lines. 

PMID- 24583699
TI  - Systematic review of published studies on safety and efficacy of thoracoscopic
      and robot-assisted lobectomy for lung cancer.
AB  - The safety and efficacy of thoracoscopic and robot-assisted lobectomies for
      primary lung cancer were reviewed in the literature. Thoracoscopic surgery is
      less invasive compared to thoracotomy, and it has been reported to be superior
      with regard to the outcome. In addition, the operability of a surgical robot (da
      Vinci) is favorable and supplements the disadvantages of conventional endoscopic
      surgery. Robot-assisted lobectomy has been reported to be comparable to
      thoracoscopic surgery with regard to the safety and efficacy based on analysis of
      perioperative results and superior with regard to the operability and length of
      the learning curve. However, a high cost and a long operative time are of
      concern. Since robot-assisted surgery has been performed only in early cases, the
      continuation of a comparative investigation may be necessary. 

PMID- 24583700
TI  - Evaluation of the optimal visceral branch configuration in open thoracoabdominal
      aortic repair by computed tomography.
AB  - BACKGROUND: In thoracoabdominal aneurysm (TAAA) repair, our technical
      modification of visceral reconstruction using longer cut pre-sewn side branches
      has provided good surgical outcomes. Here, we assessed the long-term durability
      and patency of revascularized branches using computed tomography (CT) to confirm
      the validity of our approach. METHODS: Early and late CT evaluations were
      performed in 11 TAAA patients (males: 5; mean age: 60.6 years) using the Coselli
      graft to evaluate the position of main graft and the diverging pattern and
      patency of side branches. Seven of 11 were sutured in an extra-anatomical fashion
      using longer cut side branches. RESULTS: In Anatomical (n = 4) and Extra
      anatomical (n = 7) groups, the early patency of side branches was not
      significantly different. Although the late patency of right renal artery (RA) was
      100% in both groups, the one of left RA was 60% in Extra-anatomical, while 100%
      in Anatomical. Furthermore, the main graft in Extra-anatomical was significantly
      posterior and leftward to the spine with left RA side branch diverging at an
      acute angle. CONCLUSIONS: When a pre-sewn branched graft designed for TAAA is
      used, the graft should be sutured in a fashion similar to normal patient anatomy
      to minimize the possibility of kinking of RA side branch for the patency.

PMID- 24583701
TI  - Impact of aortic cross-clamping time on peripheral nerves: experimental model.
AB  - PURPOSE: The present study investigated the correlation between extend aortic
      cross-clamping time and peripheral nerve injury on rats. METHODS: 24 male,
      Sprague Dawley rats were divided into 3 groups; (a) control group: abdomen was
      directly closed after reached aorta, and followed by 72 hours, (b) short-term
      ischaemia-reperfusion group: peripheral nerve ischemia was induced in rats by
      supraceliac aortic occlusion for 20 min followed by 72 h of reperfusion, (c) long
      term ischaemia-reperfusion group: peripheral nerve ischemia was induced for 30
      min followed by 72 h of reperfusion. Preoperative and postoperative,
      electromyography (EMG) recordings were done. End of 72 h, the sciatic nerves were
      harvested from each animal for histopathological and biochemical analysis.
      RESULTS: The mean compound muscle action potential (CMAP) amplitude of long-term
      ischaemia-reperfusion group was statically significant reduced when compared to
      the control group (p <0.01). However, the mean distal latency value of long-term
      ischaemia-reperfusion group was statically significant increased (p <0.01). On
      the other hand, there were statically significant differences between the results
      of malondialdehyde, edema and ischemia fiber degeneration grades on control and
      long-term ischaemia-reperfusion group (p <0.001). CONCLUSION: This study
      demonstrated that the extending cross clamping time directly harms the peripheral
      nerve of rats.

PMID- 24583702
TI  - Impact of intraoperative blood loss on long-term survival after lung cancer
      resection.
AB  - PURPOSE: The purpose of this study was to clarify relationships between
      intraoperative blood loss (IBL) and long-term postsurgical survival in lung
      cancer patients. METHODS: We retrospectively analyzed 1336 patients undergoing
      surgery: lobectomy in 1016, sublobar resection in 174, pneumonectomy in 106, and
      combined resection with adjacent organs in 40. The lobectomy group was stratified
      further by pathologic stages; overall survival difference was examined according
      to amount of IBL. RESULTS: Volume of IBL differed significantly according to
      surgical procedure when all patients were included. Within the lobectomy group,
      IBL differed significantly between gender, pathologic stage, histologic type
      (adenocarcinoma vs. non-adenocarcinoma), and year of operation (1983 to 2002 vs.
      2003 to 2012). After stratification by pathologic stage, survival differed with
      IBL for stages IB to IIIB. Multivariate analysis identified gender, patients age
      (<69 vs. >=69), pathologic stage (IA to IIB vs. IIIA to IV), year of operation,
      histologic type, and IBL as significant predictors of survival. CONCLUSION: Since
      degree of IBL is an independent predictor of overall survival after lung cancer
      resection, IBL should be minimized carefully during surgery.

PMID- 24583703
TI  - Usefulness of intraoperative continuous infusion of tranexamic acid during
      emergency surgery for type A acute aortic dissection.
AB  - PURPOSE: We investigated the influence of intraoperative continuous tranexamic
      acid (TA) infusion on the amount of blood transfusion required in emergency
      surgery for type A acute aortic dissection. METHODS: The study was based on the
      data of 55 consecutive patients who underwent surgery for type A acute aortic
      dissection. The patients were divided into 2 groups for comparison: Group T,
      consisting of 26 patients who received intraoperative continuous infusion of TA,
      and Group N, consisting of 29 patients who did not receive TA infusion during the
      surgery. RESULTS: The mean amounts of blood transfusion required during and after
      surgery were compared between the 2 groups: they were 10.5 +/- 8.7 and 16.2 +/-
      10.0 units of mannitol-adenine-phosphate-added red cell concentrate, 9.3 +/- 8.6
      and 17.1 +/- 10.0 units of fresh frozen plasma, and 20.4 +/- 12.2 and 29.7 +/-
      14.9 units of platelet concentrate, respectively, in Groups T and N. Thus, the
      amount of each of these blood products required was significantly reduced in
      Group T. CONCLUSIONS: During emergency surgery for type A acute aortic
      dissection, continuous infusion of TA resulted in a significant reduction in the
      amount of blood transfusion required.

PMID- 24583704
TI  - Pulmonary sequestration presenting elevated CA19-9 and CA125 with ovarian cysts.
AB  - A 41-year-old woman was evaluated because of elevated serum levels of the tumor
      markers CA19-9 and CA125. Whole-body examination revealed an intralobar pulmonary
      sequestration in the right lower lobe and bilateral cystic ovarian tumors (right:
      20 mm, left: 60 mm in diameter, respectively). The left ovarian cyst was resected
      and diagnosed as an endometrioma. The right ovarian cyst was preserved because of
      its small size. However, the tumor marker levels remained elevated
      postoperatively. S10 segmentectomy of the right lung was subsequently performed.
      Immunohistochemical examination of the sequestrated lung demonstrated positive
      staining for CA19-9 in the bronchial and alveolar epithelia and mucus. After the
      pulmonary resection, the CA19-9 and CA125 levels decreased to their normal
      ranges. 

PMID- 24583705
TI  - Density of tumor-infiltrating FOXP3+ T cells as a response marker for induction
      chemoradiotherapy and a potential prognostic factor in patients treated with
      trimodality therapy for locally advanced non-small cell lung cancer.
AB  - PURPOSE: To examine the relationship between the density of tumor-infiltrating T
      cell subpopulations and the pathological response to induction chemoradiotherapy
      (CRT) in patients with locally advanced NSCLC, and to assess the impact of T cell
      density on patient prognosis. METHODS: A total of 64 patients with c-stages IIA
      IIIB NSCLC who underwent induction CRT followed by R0 surgery were enrolled.
      Tumor-infiltrating T cells expressing either FOXP3 or CD8 were detected by
      immunohistochemical staining. RESULTS: Mean numbers of tumor-infiltrating FOXP3+
      T cells were 39.9 for patients with minor pathological responses (n = 9), 18.4
      for those with major pathological responses (n = 25), and 12.9 for those with
      complete pathological responses (n = 30; P <0.001). The number of CD8+ T cells
      was not associated with pathological responses. Patients with lower FOXP3+ T cell
      densities showed better survival, although the difference was not statistically
      significant. CONCLUSION: Our study demonstrated that the density of tumor
      infiltrating FOXP3+ T cells indicated the degree of response for induction CRT
      and prognosis in patients treated with trimodality therapy for locally advanced
      NSCLC, suggesting that FOXP3+ T cells may be target for adjunct immunotherapy.

PMID- 24583706
TI  - Prognostic significance of simultaneous presence of histological and
      immunohistochemical metastasis to lymph nodes in patients with esophageal cancer.
AB  - PURPOSE: Presence of simultaneous pathological and immunohistochemical nodal
      metastasis (pNM and iNM, respectively) and/or other clinical factors may be
      reliable prognostic predictors of survival in esophageal cancer patients who have
      undergone multidisciplinary treatment. METHODS: Univariate and multivariate
      analysis of the data collected from 77 patients who had undergone R0
      esophagectomy was performed to determine the significance of presence of iNM or
      pNM, presence of simultaneous pNM, and other clinical factors as prognostic
      indicators in patients who had (n = 40) and had not (n = 37) undergone
      preoperative treatment. RESULTS: Presence of pNM was found to be a significant
      prognostic predictor in patients who had undergone preoperative treatment,
      presence of iNM in patients who had not undergone preoperative treatment, and
      presence of simultaneous pNM and iNM in both patient groups. Multivariate
      analysis indicated that the sole prognostic predictor for patients who had
      undergone preoperative treatment was presence of simultaneous pNM and iNM while
      that of patients who had not undergone preoperative treatment was clinical T
      category. CONCLUSION: Assessment of simultaneous presence of pNM and iNM may
      facilitate highly accurate prediction of survival in esophageal cancer patients
      undergoing R0 esophagectomy, regardless of whether they have undergone
      preoperative treatment.

PMID- 24583707
TI  - Long-term outcomes of tricuspid annuloplasty for functional tricuspid
      regurgitation associated with degenerative mitral regurgitation: suture
      annuloplasty versus ring annuloplasty using a flexible band.
AB  - PURPOSE: We investigated the long-term outcomes of suture/ring tricuspid valve
      annuloplasty for functional tricuspid regurgitation associated with degenerative
      mitral regurgitation. METHODS: We retrospectively reviewed patients who underwent
      flexible ring tricuspid valve annuloplasty (n = 120) or suture tricuspid valve
      annuloplasty (n = 42) for functional tricuspid regurgitation concomitant with
      surgery for degenerative mitral regurgitation (mean follow-up duration, 5.3 +/-
      5.1 years). RESULTS: The mean age of patients was 62.5 +/- 13.1 years. Thirty-day
      mortality was zero in the suture group, and 0.8% in the ring group. Tricuspid
      regurgitation grade at discharge was lower in the ring group ( p = 0.002). No
      difference was observed between survival and freedom from major
      cardiac/cerebrovascular adverse events between the groups. However, freedom from
      >=moderate tricuspid regurgitation was higher in the ring group (Log-rank p =
      0.003). From univariate analysis, the risk factors for >=moderate TR were suture
      annuloplasty and preoperative tricuspid regurgitation grade. No reoperation for
      recurrent tricuspid regurgitation occurred in either group because symptoms
      experienced by patients with recurrent tricuspid regurgitation were relatively
      insignificant. CONCLUSION: Concomitant tricuspid annuloplasty using flexible
      bands offered improved durability than suture annuloplasty for preventing
      postoperative tricuspid regurgitation progression.

PMID- 24583708
TI  - Fast Fourier transform analysis of pulmonary nodules on computed tomography
      images from patients with lung cancer.
AB  - PURPOSE: The outlines of primary lung cancers are more complicated than those of
      metastatic lung tumors on computed tomography (CT) images. This feature is useful
      for clarifying the diagnosis of pulmonary nodules before surgery. We applied fast
      Fourier transform (FFT) analysis for quantification of complexity of tumor
      outline. METHODS: Sequential cases of 72 primary lung cancers (Group PL) and 54
      metastatic lung tumors (Group MT) were included. The outline of each tumor on
      chest CT images was described using polar coordinates, and converted to
      rectangular coordinates, yielding wave data of the tumor outline. The FFT was
      then used to analyze the wave data. The complexity index (Cxi) was defined as the
      sum of the amplitude of all harmonics over a fundamental frequency. RESULTS: The
      Cxi was higher (P <0.0001) for group PL (10.3 +/- 6.7 mm) than for group MT (3.2
      +/- 2.4 mm), and it was correlated with tumor diameter in both groups. The cut
      off equation "Cxi = 0.127 DT + 2.23" provided the highest diagnostic accuracy for
      distinguishing Group PL from Group MT such as a sensitivity of 95.8%, a
      specificity of 81.5%, and an accuracy of 89.7%. CONCLUSION: FFT analysis appears
      useful for quantification of complexity of the tumor outline.

PMID- 24583709
TI  - Radiofrequency ablation for pulmonary metastases from gastrointestinal cancers.
AB  - The lung is one of the most common targets of metastases from gastrointestinal
      (GI) cancers. Surgical treatment (i.e., metastasectomy) is an accepted
      therapeutic option for pulmonary metastases from GI cancers. However, surgery may
      be contraindicated in advanced stages of cancer, compromised lung function,
      and/or comorbidities. This issue has prompted the search for innovative and less
      invasive ways of treating pulmonary metastases. Image-guided radiofrequency
      ablation (RFA) has attracted great interest as a minimally invasive approach
      against intrathoracic malignancies. In this technique, radiofrequency energy is
      applied via a needle electrode inserted into the target tissue. As the cells are
      agitated by the applied energy, they release heat, causing denaturation and cell
      death. Recently, this technique has been used on patients with pulmonary
      metastatic disease arising from GI cancers such as colorectal cancer, esophageal
      cancer, and hepatocellular carcinoma, as well as on patients with primary lung
      cancer. The present review updates the clinical outcomes and advances in RFA
      therapy of lung metastases from GI cancers. 

PMID- 24583711
TI  - Modelling segregation effects of heterogeneous emissions on ozone levels in
      idealised urban street canyons: using photochemical box models.
AB  - Air quality models include representations of pollutant emissions, which
      necessarily entail spatial averaging to reflect the model grid size; such
      averaging may result in significant uncertainties and/or systematic biases in the
      model output. This study investigates such uncertainties, considering ozone
      concentrations in idealised street canyons within the urban canopy. A
      photochemical model with grid-averaged emissions of street canyons is compared
      with a multiple-box model considering each canyon independently. The results
      reveal that the averaged, 'one-box' model may significantly underestimate true
      (independent canyon mean) ozone concentrations for typical urban areas, and that
      the performance of the averaged model is improved for more 'green' and/or less
      trafficked areas. Our findings also suggest that the trends of 2005-2020 in
      emissions, in isolation, reduce the error inherent in the averaged-emissions
      treatment. These new findings may be used to evaluate uncertainties in modelled
      urban ozone concentrations when grid-averaged emissions are adopted. 

PMID- 24583710
TI  - Impact of soil amendments and the plant rhizosphere on PAH behaviour in soil.
AB  - Carbonaceous amendments reduce PAH dissolved concentrations (Cfree), limiting
      their uptake and toxicity. A soil contaminated with PAHs was mixed with activated
      carbon (AC), charcoal or compost and planted with radish (Raphanus sativus L.),
      and Cfree, chemical activities and diffusive uptake of the PAHs measured over 2
      months. For AC, Cfree and diffusive uptake were decreased by up to 94% compared
      to the unamended soil within one week. In addition, the sum chemical activity of
      the PAHs remained below the threshold for baseline toxicity. In contrast,
      charcoal and compost only led to modest reductions in Cfree and diffusive uptake,
      with sum chemical activities that could potentially result in baseline toxicity
      being observed. Furthermore, both Cfree and diffusive uptake were lower in the
      planted compared to unplanted soils. Therefore, only AC successfully reduced PAH
      acute toxicity in the soil, but plant-promoted microbial degradation may also
      play an important role in PAH attenuation. 

PMID- 24583712
TI  - Soil acidification increases metal extractability and bioavailability in old
      orchard soils of Northeast Jiaodong Peninsula in China.
AB  - The bioavailability of Cu, Zn, Pb and Cd from field-aged orchard soils in a
      certified fruit plantation area of the Northeast Jiaodong Peninsula in China was
      assessed using bioassays with earthworms (Eisenia fetida) and chemical assays.
      Soil acidity increased with increasing fruit cultivation periods with a lowest pH
      of 4.34. Metals were enriched in topsoils after decades of horticultural
      cultivation, with highest concentrations of Cu (132 kg(-1)) and Zn (168 mg kg(
      1)) in old apple orchards and Pb (73 mg kg(-1)) and Cd (0.57 mg kg(-1)) in
      vineyard soil. Earthworm tissue concentrations of Cu and Pb significantly
      correlated with 0.01 M CaCl2-extractable soil concentrations (R(2) = 0.70, p <
      0.001 for Cu; R(2) = 0.58, p < 0.01 for Pb). Because of the increased
      bioavailability, regular monitoring of soil conditions in old orchards and
      vineyards is recommended, and soil metal guidelines need reevaluation to afford
      appropriate environmental protection under acidifying conditions. 

PMID- 24583713
TI  - Do PI3-kinase mutations drive T cells insane?

PMID- 24583714
TI  - NADPH oxidase 4 represents a potential target for the treatment of osteoporosis.

PMID- 24583717
TI  - NTP nonneoplastic lesion atlas: a new tool for toxicologic pathology.

PMID- 24583715
TI  - Phenotypes of Th lineages generated by the commonly used activation with anti
      CD3/CD28 antibodies differ from those generated by the physiological activation
      with the specific antigen.
AB  - T-helper (Th) lineages have been generated in vitro by activating CD4 cells with
      anti-CD3/CD28 antibodies during polarization. Physiologically, however, the
      generation of Th lineages is by activation with the specific antigen presented by
      antigen-presenting cells (APC). Here, we used T-cell receptor (TCR)-transgenic
      mice to compare the phenotypes of Th1, Th9 and Th17 lineages when generated by
      either one of the two activation modes. Lineage Th cells specific against hen egg
      lysozyme (HEL), were adoptively transferred into recipient mice transgenically
      expressing HEL in their lens. Remarkable differences were found between lineages
      of Th1, Th9 or Th17, generated by either one of the two modes in their capacities
      to migrate to and proliferate in the recipient spleen and, importantly, to induce
      inflammation in the recipient mouse eyes. Substantial differences were also
      observed between the lineage pairs in their transcript expression profiles of
      certain chemokines and chemokine receptors. Surprisingly, however, close
      similarities were observed between the transcript expression profiles of lineages
      of the three phenotypes, activated by the same mode. Furthermore, Th cell
      lineages generated by the two activation modes differed considerably in their
      pattern of gene expression, as monitored by microarray analysis, but exhibited
      commonality with lineages of other phenotypes generated by the same activation
      mode. This study thus shows that (i) Th lineages generated by activation with
      anti-CD3/CD28 antibodies differ from lineages generated by antigen/APC; and (ii)
      the mode of activation determines to a large extent the expression profile of
      major transcripts. 

PMID- 24583720
TI  - Letters.

PMID- 24583718
TI  - Radiographical and Clinical Outcomes of Posterior Column Osteotomies in Spinal
      Deformity Correction.
AB  - STUDY DESIGN: Prospectively enrolled, retrospectively analyzed case series.
      OBJECTIVE: To evaluate a large series of pediatric patients/patients with adult
      spinal deformity undergoing surgery with posterior column osteotomies (PCOs).
      SUMMARY OF BACKGROUND DATA: Osteotomies of the posterior column (Smith-Petersen
      or Ponte) are used to reduce kyphosis, increase lordosis, or increase spinal
      flexibility. However, little focused evidence exists regarding the efficacy and
      safety of this technique. METHODS: A total of 128 consecutive patients underwent
      posterior spinal fusion with PCOs with minimum 2-year follow-up. Seventy-five
      were primary surgical procedures; 53 were revisions. Data were collected from
      hospital charts, clinic notes, radiographs, and standardized questionnaires
      (Scoliosis Research Society-30 and Oswestry Disability Index). RESULTS: A total
      of 128 patients aged 37.6 +/- 21 years underwent 518 PCOs (mean, 4.0 +/- 2.2 yr)
      with 14.4 +/- 3 mean instrumentation levels, with 3-year (range, 2-6.8 yr)
      average follow-up. PCOs were used for kyphosis correction in 49%, scoliosis
      correction at the apex of a curve in 13%, and both in 38%. One hundred six
      patients had complete radiographical data available for evaluation. Mean kyphosis
      correction per PCO was 8.8 degrees  +/- 7.2 degrees , varying with patient age
      (10.2 degrees  for those younger than 21 yr vs. 7.7 degrees  for those 21 yr or
      older, P < 0.0001) and region of the spine: thoracolumbar (T10-L2) 11.6 degrees ,
      lumbar (L2-S1) 9.4 degrees , midthoracic (T6-T10) 7.2 degrees  and proximal
      thoracic (T1-T6) 3.6 degrees . With PCOs at the apex of a curve, the maximum
      coronal Cobb decreased from 66 degrees  +/- 21 degrees  to 31 degrees  +/- 14
      degrees  (P < 0.0001). Average estimated blood loss was 1419 +/- 887 mL,
      correlating with greater age (P < 0.0001) and more instrumented levels (P <
      0.0001), but not with the number of PCOs (P = 0.32). Complications occurred in 31
      (24.2%) patients, including 4 radiculopathies (none attributable to PCOs).
      Complications did not correlate with the number of PCOs (P = 0.5). Six (4.7%)
      patients had loss of spinal cord monitoring or a failed wake-up test that could
      be attributed to overcorrection with PCOs, but none had postoperative deficits.
      Oswestry Disability Index scores improved (34.4 +/- 17 to 23.6 +/- 18, P <
      0.0001), as did normalized Scoliosis Research Society-30 scores (63.7 +/- 13 to
      76.4 +/- 15, P < 0.0001). CONCLUSION: Patients in this series undergoing
      posterior spinal fusion with PCOs achieved overall favorable outcomes for spinal
      deformity correction. The number of PCOs did not correlate with increased
      estimated blood loss or complications. The main technical concern was
      overcorrection, but neurological consequences associated with overcorrection were
      identified by intraoperative spinal cord monitoring and wake-up tests, and no
      patients experienced permanent neurological deficits related to PCOs. LEVEL OF
      EVIDENCE: 4.

PMID- 24583721
TI  - Letters.

PMID- 24583722
TI  - Identification of Risk Factors for the Occurrence of Cement Leakage During
      Percutaneous Vertebroplasty for Painful Osteoporotic or Malignant Vertebral
      Fracture.
AB  - STUDY DESIGN: Retrospective study. OBJECTIVE: To identify fracture morphology
      dependent risk factors for the occurrence of cement leakage during percutaneous
      vertebroplasty. SUMMARY OF BACKGROUND DATA: Extravertebral cement leakage is the
      most frequently reported complication and represents a major risk after
      vertebroplasty and balloon kyphoplasty. Despite the frequent occurrence of cement
      leakage and potentially dangerous complications and sequelae, there are few
      reports that examine its predictors. METHODS: Retrospective review of 194
      consecutive patients who underwent percutaneous vertebroplasty for painful
      osteoporotic or malignant vertebral fracture. The influences of several
      parameters that might affect the occurrence of cement leakage were assessed using
      univariate and multivariate analyses. Cement leakage was assessed using computed
      tomography scanning and classified into 4 different types with different
      potential sequelae: through the basivertebral vein, through the segmental vein,
      through a cortical defect, and intradiscal leakage. RESULTS: Leakage of cement
      was detected in 209 of the 272 treated vertebrae (76.83%). The most common types
      of leakage detected were through the basivertebral vein (43.38%) and the
      segmental vein (42.27%). None of the evaluated variables showed a statistically
      significant effect. Only the absence of Kummell disease (P = 0.063) and a lower
      severity grade of collapse (P = 0.068) approached statistical significance. For
      basivertebral vein leakages, the location at the thoracolumbar level and the
      absence of Kummell disease (P < 0.05) were strong predictive factors for cement
      leakages. For segmental vein leakages, the odds decreased as the severity grade
      of collapse increased (P = 0.008). CONCLUSION: Each different vertebral fracture
      pattern has its own risk factors for cement leakage. For certain types of
      leakage, Kummell avascular necrosis as a protective factor and fracture severity
      grade with paradoxical effect have each demonstrated influence in the occurrence
      of cement leakage. LEVEL OF EVIDENCE: 4.

PMID- 24583716
TI  - The macrophage soluble receptor AIM/Api6/CD5L displays a broad pathogen
      recognition spectrum and is involved in early response to microbial aggression.
AB  - Apoptosis inhibitor of macrophages (AIMs), a homologue of human Spalpha, is a
      mouse soluble member of the scavenger receptor cysteine-rich superfamily (SRCR
      SF). This family integrates a group of proteins expressed by innate and adaptive
      immune cells for which no unifying function has yet been described. Pleiotropic
      functions have been ascribed to AIM, from viability support in lymphocytes during
      thymic selection to lipid metabolism and anti-inflammatory effects in autoimmune
      pathologies. In the present report, the pathogen binding properties of AIM have
      been explored. By using a recombinant form of AIM (rAIM) expressed in mammalian
      cells, it is shown that this protein is able to bind and aggregate Gram-positive
      and Gram-negative bacteria, as well as pathogenic and saprophytic fungal species.
      Importantly, endogenous AIM from mouse serum also binds to microorganisms and
      secretion of AIM was rapidly induced in mouse spleen macrophages following
      exposure to conserved microbial cell wall components. Cytokine release induced by
      well-known bacterial and fungal Toll-like receptor (TLR) ligands on mouse
      splenocytes was also inhibited in the presence of rAIM. Furthermore, mouse models
      of pathogen-associated molecular patterns (PAMPs)-induced septic shock of
      bacterial and fungal origin showed that serum AIM levels changed in a time
      dependent manner. Altogether, these data suggest that AIM plays a general
      homeostatic role by supporting innate humoral defense during pathogen aggression.

PMID- 24583723
TI  - Potential use of diffusion tensor imaging in level diagnosis of multilevel
      cervical spondylotic myelopathy.
AB  - STUDY DESIGN: A prospective study on a series of consecutive patients. OBJECTIVE:
      To investigate the use of diffusion tensor imaging (DTI) and orientation entropy
      in level localization in patients diagnosed with multilevel cervical spondylotic
      myelopathy (CSM). SUMMARY OF BACKGROUND DATA: Multilevel CSM presents complex
      neurological signs that make level localization difficult. DTI is recently found
      to be able to assess the microstructural changes of the white matter caused by
      cord compression. METHODS: Sixteen patients with CSM with multilevel compression
      were recruited. The level(s) responsible for the clinical symptoms were
      determined by detailed neurological examination, T2-weighted (T2W) magnetic
      resonance imaging (MRI), and DTI. On T2W MRI, anterior-posterior compression
      ratio and increased signal intensities were used to determine the affected
      level(s). The level diagnosis results from T2W MRI, increased signal intensities,
      DTI, and combination method were correlated to that of neurological examination
      on a level-to-level basis, respectively. The accuracy, sensitivity, and
      specificity were calculated. RESULTS: When correlated with the clinical level
      determination, the weighted orientation entropy-based DTI analysis was found to
      have higher accuracy (82.76% vs. 75.86%) and sensitivity (84.62% vs. 76.92%) than
      those of the anterior-posterior compression ratio. The increased signal
      intensities have the highest specificity (100.00%) but the lowest accuracy
      (58.62%) and sensitivity (53.85%). When combined with the level diagnosis result
      of wOE with that of anterior-posterior compression ratio, it demonstrated the
      highest accuracy and sensitivity that were 93.10% and 96.15%, respectively, and
      equal specificity (66.67%) with using them individually. CONCLUSION: DTI can be a
      useful tool to determine the pathological spinal cord levels in multilevel CSM.
      This information from orientation entropy-based DTI analysis, in addition to
      conventional MRI and clinical neurological assessment, should help spine surgeons
      in deciding the optimal surgical strategy.

PMID- 24583724
TI  - Prior abdominal surgery is associated with an increased risk of postoperative
      complications after anterior lumbar interbody fusion.
AB  - STUDY DESIGN: Retrospective medical record review. OBJECTIVE: The purpose of this
      study was to determine whether a history of abdominal/pelvic surgery confers an
      increased risk of retroperitoneal anterior approach-related complications when
      undergoing anterior lumbar interbody fusion. SUMMARY OF BACKGROUND DATA: As
      anterior lumbar interbody fusion gains popularity, both anterior retroperitoneal
      approach have become increasingly used. METHODS: The records of 263 patients, who
      underwent infraumbilical retroperitoneal approach to the anterior aspect of the
      lower lumbar spine for a degenerative spine condition between 2007 and 2011 were
      retrospectively reviewed. Patient's demographics, risk factors, preoperative
      diagnosis, surgical history, level of the anterior fusion, and perioperative
      complications were collected. Anterior retroperitoneal approach to the spine was
      carried out by a single general surgeon. RESULTS: Ninety-seven patients (37%)
      developed at least 1 complication. Forty-nine percent of patients with a history
      of abdominal surgery developed a postoperative complication compared with 28% of
      patients without such history (RR = 1.747, P<= 0.001). After controlling for
      other factors such as age, sex, body mass index, diagnostic groups, and
      preoperative comorbidities (hypertension, diabetes, and smoking status), these
      differences remained statistically significant. When each type of complication
      was considered separately, there was a statistically significant difference in
      the incidence of general complications (RR = 2.384, P = 0.007), instrumentation
      related complications (RR = 2.954, P = 0.010), and complications related to the
      anterior approach (RR = 1.797, P = 0.021). CONCLUSION: Anterior lumbar interbody
      fusion via a midline incision and a retroperitoneal approach was associated with
      37% overall rate of complication. Patients with a history of abdominal or pelvic
      surgery are at a higher risk of developing general, instrumentation, and anterior
      approach-related complications.

PMID- 24583726
TI  - Biomechanical Evaluation of a Novel Autogenous Bone Interbody Fusion Cage for
      Posterior Lumbar Interbody Fusion in a Cadaveric Model.
AB  - STUDY DESIGN: A human cadaveric biomechanical study of a novel, prefabricated
      autogenous bone interbody fusion (ABIF) cage. OBJECTIVE: To evaluate the
      biomechanical properties of the ABIF cage in a single-level construct with and
      without transpedicular screw and rod fixation. SUMMARY OF BACKGROUND DATA: In
      current practice, posterior lumbar interbody fusion is generally carried out
      using synthetic interbody spacers or corticocancellous iliac crest bone graft
      (ICBG) in combination with posterior instrumentation. However, questions remain
      concerning the use of synthetic intervertebral implants as well as the morbidity
      ICBG harvesting. Therefore, ABIF cage has been developed to obviate some of the
      challenges in conventional posterior lumbar interbody fusion instrumentation and
      to facilitate the fusion process. METHODS: Eighteen adult cadaveric lumbosacral
      (L3-S1) specimens were tested. Test conditions included single lumbosacral
      segments across (1) intact, (2) decompressed, (3) intervertebral cage alone, and
      (4) intervertebral cage with bilateral transpedicular fixation. Range of motion
      (ROM), neutral zone (NZ), and axial failure load were tested for each condition.
      RESULTS: The ICBG, polyetheretherketone cage, or ABIF cage alone exhibited a
      significantly lower (P < 0.05) ROM and NZ than the decompressed spine. In
      comparison with the intact spine, all 3 test conditions without supplemental
      fixation were able to decrease ROM and NZ to near intact levels. When stabilized
      with pedicle screws, the ROM was significantly less and the NZ was significantly
      lower (P < 0.05) for each group both compared with the intact spine. In axial
      compression testing, the failure load of polyetheretherketone cage was the
      highest, with no significant difference between the ICBG and the ABIF cage.
      CONCLUSION: These data suggest that the novel ABIF cage can bear the
      physiological intervertebral peak load, similar to ICBG. When combined with
      pedicle screw and rod fixation, it exhibits similar biomechanical properties as
      the polyetheretherketone cage plus posterior instrumentation. Based on the
      biomechanical properties of ABIF cage, the prospect of these cages in clinical
      practice is expected.

PMID- 24583725
TI  - Risk factors for missed dynamic canal stenosis in the cervical spine.
AB  - STUDY DESIGN: Retrospective analysis of kinematic magnetic resonance (MR) images.
      OBJECTIVE: To elucidate the distribution and risk factors associated with missed
      dynamic stenosis in cervical spine. SUMMARY OF BACKGROUND DATA: Motion of the
      cervical spine is widely accepted to be associated with cervical spondylotic
      myelopathy; however, the distribution and the risk factors for dynamic spinal
      stenosis are not well understood. METHODS: A total of 435 symptomatic patients
      (2610 cervical segments) obtained upright kinematic MR images in neutral,
      flexion, and extension postures. Spinal cord compression (SCC),
      spondylolisthesis, disc bulging, angular motion, translational motion, disc
      degeneration grade, Modic changes, segmental alignment, and developmental
      stenosis were all evaluated. Cervical segments C2-C3 to C7-T1 were divided into 2
      groups, determined by the presence of SCC. After excluding segments with SCC in
      the neutral position, a multivariate logistic regression model was used to
      evaluate for associated risk factors of SCC in flexion and extension that were
      not present in the neutral position. RESULTS: SCC in neutral position was
      observed in 5.3% (139/2610) of segments. After excluding these segments, missed
      dynamic stenosis was found in 8.3% (204/2471) of segments in extension and 1.6%
      (40/2471) in flexion. Missed dynamic stenosis in both extension and flexion was
      most frequent at C5-C6. Multivariate logistic regression analysis for dynamic
      stenosis in extension revealed that disc bulge greater than 2.4 mm, angular
      motion greater than 4.8 degrees , moderate and severe disc degeneration,
      segmental kyphosis, and developmental stenosis were significant risk factors. In
      flexion, significant risk factors were a disc bulge of 1.9 mm or greater,
      moderate to severe disc degeneration, and segmental kyphosis. CONCLUSION: Dynamic
      cord compression was most common at the C5-C6 segment. Cervical segments with
      greater disc bulge, more severe disc degeneration, greater angular motion,
      segmental kyphosis, and developmental stenosis may be at risk for missed dynamic
      stenosis.

PMID- 24583727
TI  - Prevalence and countermeasures for venous thromboembolic diseases associated with
      spinal surgery: a follow-up study of an institutional protocol in 209 patients.
AB  - STUDY DESIGN: A prospective study of 209 patients undergoing spinal surgery.
      OBJECTIVE: To determine the incidence of venous thromboembolic diseases,
      including deep venous thrombosis (DVT) and pulmonary embolism (PE), and to
      evaluate the effectiveness of an institutional protocol for venous thromboembolic
      diseases during the spinal surgery perioperative period. SUMMARY OF BACKGROUND
      DATA: Although patients undergoing spinal surgery are at risk of venous
      thromboembolism (VTE), there are no universally accepted guidelines for VTE
      prophylaxis. METHODS: Between December 2006 and January 2011, 209 patients
      undergoing spinal surgery (121 males, 88 females; average age: 64 yr), who also
      had ultrasonographic assessments of both legs before and after surgery, were
      prospectively assessed. A pneumatic sequential compression device and standard
      compression stockings were used for primary VTE prophylaxis. In Mie University
      Hospital protocol, pharmacological agents were not used for VTE prophylaxis after
      surgery. However, when a distal type DVT was found preoperatively, an
      anticoagulant medication was administered until 6 hours prior to surgery. After
      detection of DVTs, weekly ultrasonography assessed the DVT. RESULTS: Twenty-three
      patients (11.0%) showed VTE in the spinal surgery perioperative period. Nine
      patients (4.3%) had VTE (PE with proximal DVT, 1 [0.5%]; distal DVT, 8 [3.8%])
      before surgery. In the one case of asymptomatic PE with proximal DVT, an inferior
      vena cava filter was placed before surgery. Fourteen patients (6.7%) developed
      new-onset VTE (PE with proximal DVT, 2 [1.0%]; distal DVT, 12 [5.9%]) after
      spinal surgery. New-onset PE with proximal DVT occurred in 2 patients after
      surgery. Follow-up ultrasonographic assessment showed that the DVT disappeared
      completely in 85% (17/20) of patients with a distal type DVT during the
      perioperative period. CONCLUSION: DVT assessment using ultrasonography is
      important for proper management of VTE during the perioperative period of spinal
      surgery, especially for high-risk patients, such as those with advanced age or
      neurological deficit. The institutional protocol for VTE using pneumatic
      sequential compression device and compression stockings is effective, although
      the administration of chemoprophylaxis should be considered for high-risk
      patients, such as those with spinal tumors and spinal trauma.

PMID- 24583728
TI  - Comparative analysis of clinical outcomes and complications in patients with
      degenerative scoliosis undergoing primary versus revision surgery.
AB  - STUDY DESIGN: Retrospective cohort analysis of prospectively collected data.
      OBJECTIVE: To compare clinical outcomes and postoperative complications in
      patients with lumbar degenerative scoliosis who underwent primary (P) versus
      revision (R) surgery. SUMMARY OF BACKGROUND DATA: Revision surgery for spinal
      deformity is technically challenging and may be associated with greater risks of
      complications and inferior clinical outcomes. There is a paucity of data in the
      literature comparing primary versus revision surgery in patients with
      degenerative scoliosis with respect to their clinical outcomes and complications.
      METHODS: An analysis of 84 consecutive patients with degenerative scoliosis who
      underwent primary versus revision surgery between 2002 and 2010 with a minimum 2
      year follow-up was performed. RESULTS: There were 53 patients in the primary
      group and 31 in the revision group. The average number of previously operated
      levels in the revision group was 3.5 +/- 2.6. Mean age at surgery, sex, and body
      mass index were similar between the 2 groups, as well as comorbidities and
      postoperative complication rates (P > 0.05). Although a greater preoperative
      coronal imbalance was noticed in the revision group (P: 2.5 cm vs. R: 4.8 cm, P =
      0.022), the final radiographical measures were comparable between the 2 groups.
      At 2-year follow-up, Oswestry Disability Index and visual analogue scale scores
      improved significantly in both groups compared with preoperatively (P < 0.001).
      The improvement in scores of Oswestry Disability Index and visual analogue scale
      preoperatively to final follow-up was similar between the 2 groups (P > 0.05).
      CONCLUSION: Revision patients achieved the same radiographical and clinical
      outcomes as primary patients. The complication rates were similar between primary
      and revision patients. Revision patients benefit from surgery just as much as
      primary patients at 2-year follow-up.

PMID- 24583729
TI  - Revision Surgery After 3-Column Osteotomy in 335 Patients With Adult Spinal
      Deformity: Intercenter Variability and Risk Factors.
AB  - STUDY DESIGN: Multicenter, retrospective review. OBJECTIVE: To assess rates, site
      variability, and risk factors for revision surgery (RS) after 3-column osteotomy
      (3CO). SUMMARY OF BACKGROUND DATA: Complex spinal osteotomies, including 3CO, are
      being increasingly performed in the setting of patients with adult spinal
      deformity with sagittal plane deformity. Three-column osteotomy procedures are
      associated with high complication and RS rates, but risk factors for
      complications and variability across centers for revision have not been well
      defined. METHODS: The incidence and indications for RS in 335 patients with adult
      spinal deformity were analyzed. RS indications were classified as "mechanical"
      (MR: implant failure, pseudarthrosis, junctional failure, and loss/lack of
      correction) or "nonmechanical" (NMR: neurological deficit, infection, wound
      dehiscence, and stenosis). Risks factors for RS were analyzed using generalized
      linear models. RESULTS: Three-month and 1-year RS incidences were 12.3% and
      17.6%, respectively. Single-level 3CO (n = 311) had lower RS rates than
      multilevel 3CO (n = 24, 15.8% vs. 41.7%, P = 0.001). The 16.7% rate for single
      level lumbar 3CO included 11.4% for MR and 5.7% for NMR. For all RS, 50% of MR
      and 78.6% of NMR occurred within 3 months of the index surgery. There was
      significant variation in rates across sites (range = 6.3%-31.9%, P = 0.001),
      however low- and high-volume sites had similar rates (18.2% vs. 16.2%, P =
      0.503). Patients with MR were more likely to be sagittally undercorrected at 3
      months (sagittal vertical axis = 7 cm vs. 3.2 cm, P = 0.003). Patients with NMR
      had more caudal 3CO levels (L4 vs. L3, P = 0.014) and larger 3CO bone resections
      than patients who did not (34 degrees vs. 24.5 degrees , P = 0.003). CONCLUSION:
      Three-column osteotomy procedures for adult spinal deformity surgery can provide
      significant deformity correction and lead to marked improvement in function
      despite established complication and revision rates. This study shows that RS is
      associated with lower level osteotomy and higher residual sagittal vertical axis.
      There is significant variability in revision rates across sites independent of
      site volume, suggesting potential systems and practice variations that warrant
      further study. LEVEL OF EVIDENCE: 4.

PMID- 24583730
TI  - Accuracy of magnetic resonance imaging signal intensity ratio measurements in the
      evaluation of multifidus muscle injury and atrophy relative to that of
      histological examinations.
AB  - STUDY DESIGN: A matched-pairs animal study. OBJECTIVE: To confirm the accuracy of
      magnetic resonance imaging (MRI) as a means of evaluating edema and fat
      degeneration of the multifidus muscle by comparing measurements made using MRI
      with those made using histological examination. SUMMARY OF BACKGROUND DATA: MRI
      is considered a reliable means of evaluating multifidus muscle edema and fat
      degeneration. However, it is not clear whether its results are always consistent
      with histological findings. METHODS: Models of different degrees of multifidus
      injury were created at the L2-L3, L3-L4, and L4-L5 disc levels in 56 New Zealand
      white rabbits. These were divided into 4 groups and subjected to different
      processes: sham surgery, dissection and stripping of the multifidus, crushing of
      the muscle lasting 1 hour, and crushing of the muscle lasting 2 hours. Two
      rabbits per group were examined at each of the indicated points in time.
      Multifidus edema was assessed using fat-suppressed T2 signal intensity ratio of
      gross multifidus to psoas (T2R) on MRI bilaterally, wet weight and wet:dry weight
      ratio on the left side (edema-left), and visual edema score on the right side
      (edema-right). Muscle fat degeneration was detected bilaterally using the T1
      signal intensity ratio of gross multifidus to psoas with MRI (T1R) and visual fat
      degeneration score (fat score) with histology. RESULTS: Pearson correlation
      coefficient analyses showed significant correlations (P < 0.001) between left T2R
      and edema-left (r = 0.927), right T2R and edema-right (r = 0.868), and T1R and
      fat score (r = 0.804). A paired t test demonstrated no significant differences
      between MRI measurements and histological changes (P = 0.999, 1.000, and 0.998).
      Bland-Altman plots also depicted good agreement between MRI measurements and
      histological changes (limits of agreement: left multifidus edema, +/- 0.75; right
      multifidus edema, +/- 1.01; fat degeneration, +/- 1.23). CONCLUSION: The MRI
      technique is an accuracy means of evaluating multifidus muscle injury and
      atrophy.

PMID- 24583732
TI  - Dynamic stability of the trunk during unstable sitting in people with low back
      pain.
AB  - STUDY DESIGN: Cross-sectional study. OBJECTIVE: To evaluate the dynamic stability
      and kinematics of the trunk during unstable sitting, and to determine the
      differences in these biomechanical parameters between healthy participants and
      participants with low back pain (LBP). SUMMARY OF BACKGROUND DATA: Patients with
      LBP exhibited alterations in trunk kinematics while performing different dynamic
      tasks and in static posture as a result of pain. It is not clear if changing in
      trunk motion may reduce postural control and the ability to perform a balancing
      task. METHODS: Twenty-three participants with LBP and 31 healthy participants
      were requested to sit on a custom-made swinging chair and to regain the balance
      after tilting the chair backward for 10 degrees  and 20 degrees . Lumbar spine,
      pelvis, and chair motions were recorded using FASTRAK sensors. The thoracolumbar
      curvature of all participants was also evaluated in the standing position. The
      angular displacement of the chair was fitted in an equation describing the
      underdamped second-order response to a step input. RESULTS: Kinematic analysis
      showed that the hip range of motion increased whereas spine range of motion angle
      decreased in participants with LBP for both tilt angles (P < 0.05). There were no
      significant differences between the 2 subject groups in the time required to
      regain balance, and the natural frequency and damping ratio of the kinematic
      equation. Lumbar lordosis significantly decreased in LBP group. CONCLUSION:
      Participants with LBP showed trunk postural and movement adaptations that seems
      to be compensatory strategies to decrease the risk of further injuries and
      aggravation of the symptoms, but their ability to regain the balance was not
      affected by LBP. Clinicians should encourage patients with LBP to remain active
      while they are experiencing pain.

PMID- 24583733
TI  - Scoliosis research society-22 results in 3052 healthy adolescents aged 10 to 19
      years.
AB  - STUDY DESIGN: Cross-sectional survey. OBJECTIVE: The purpose of our study was to
      evaluate a large population of adolescents from a broad mix of racial/ethnic
      backgrounds and age groups to better establish baseline normative values for the
      Scoliosis Research Society-22 (SRS-22). SUMMARY OF BACKGROUND DATA: The SRS-22
      instrument was developed to assess treatment outcomes in patients with adolescent
      idiopathic scoliosis. To accurately assess real changes in outcome measures, the
      SRS-22 must be able to differentiate patients with and without adolescent
      idiopathic scoliosis. METHODS: The SRS-22 was administered to 3052 healthy
      adolescents, 51% female and 49% male, with a mean age of 14.6 years (range, 10-19
      yr). We grouped the children into 3 age groups for analysis: 10 to 12 years
      (362), 13 to 15 years (1487), and 16 to 19 years (1203). Racial/ethnic groups
      included: Caucasian, 62%; African American, 14%; Hispanic, 9%; Asian, 6%; Native
      American, 5%; and Pacific Islander, 4%. SRS-22 scores were analyzed to establish
      normative values for each group. RESULTS: Mean SRS-22 scores were: activity,
      (4.31 +/- 0.54); pain, (4.44 +/- 0.67); image, (4.41 +/- 0.64); mental, (3.96 +/-
      0.81); and total, (4.26 +/- 0.54). Females had lower scores in the mental domain
      (3.90) than males (4.04) (P < 0.001). The scores of children aged 10 through 12
      years were higher in the domains of activity (P = 0.000), pain (P < 0.001), and
      mental (P < 0.001) than those of children aged 13 through 15 years and 16 through
      19 years. The 13- to 15-year group had significantly higher scores than the 16-
      to 19-year group (P < 0.001) in each of the same categories. Regarding
      race/ethnicity, Caucasians tended to report higher scores in most domains than
      other race/ethnic groups. Hispanics scored lower in all domains than the non
      Hispanic group. CONCLUSION: Age, sex, and race had a significant impact on SRS-22
      scores in a large group of healthy adolescents. In general, scores lowered as age
      increased from 10 to 19 years, Caucasians scored higher in function, pain, and
      image than other racial groups, and Hispanics scored lower than non-Hispanics in
      all domains. These factors should be considered when evaluating SRS-22 scores.

PMID- 24583734
TI  - Effect of Pentoxifylline on Spinal Fusion: An Experimental Study in Rabbits.
AB  - STUDY DESIGN: Randomized, double-blinded, animal model. OBJECTIVE: The objective
      of this study is to evaluate the effect of pentoxifylline (PTX) on spinal fusion
      in a rabbit model. SUMMARY OF BACKGROUND DATA: Previous studies assert that PTX
      increases new bone formation. Because PTX seems to have these profound effects on
      bone metabolism, it may be hypothesized that it may enhance spinal fusion.
      METHODS: Twenty-four New Zealand white rabbits were randomized and each received
      single-level posterolateral, inter-transverse process fusion with autologous
      iliac crest. In group 1, 12 male New Zealand white rabbits were treated with
      intravenous PTX treatment in 100-mg/kg/day dose after the surgical procedure. In
      group 2, 12 received no PTX medication and were accepted as the control group.
      Nine weeks after surgery, the animals were killed. The spines were tested via a
      manual palpation test, biomechanical testing, plain radiography, computed
      tomographic scans, and histomorphometric analysis. RESULTS: The fusion rates of
      manual palpation were 40% in the control group and 80% in the PTX group (P =
      0.17). Using a 5-grade radiographical system, the mean fusion grade was 2.4 in
      the control group and 3.1 in PTX group (P = 0.012). Total displacement of the
      fused level for the control group under flexion and extension was 0.2515 mm and
      was lower for the PTX-treated group: 0.1266 mm (P = 0.012). In the control group,
      the mean bone volume of the fusion mass determined from computed tomographic
      analysis was 4.0678 cm, whereas in the PTX group it was 4.7802 cm (P = 0.009).
      The mean trabecular bone area was 14% and 19% for the control and PTX groups,
      respectively (P = 0.002). CONCLUSION: The differences between groups was
      statistically significant in terms of radiological fusion grading, biomechanical
      testing, volume of the fusion mass, and percentage of trabecular bone area. These
      results suggest that PTX may have a beneficial effect on spinal fusion. LEVEL OF
      EVIDENCE: 2.

PMID- 24583735
TI  - Inconsistencies between abstracts and manuscripts in published studies about
      lumbar spine surgery.
AB  - STUDY DESIGN: Systematic review. OBJECTIVE: To perform a comparison of randomized
      controlled trial (RCT) abstracts and manuscripts published in recent spinal
      literature. SUMMARY OF BACKGROUND DATA: RCTs represent the "gold standard" upon
      which evidence-based treatment decisions are made. Inconsistencies between an
      abstract and manuscript can mislead readers' interpretation of findings and
      conclusions. Abstract findings are often cited without reference to the
      manuscript itself. In other fields of medicine, studies have shown discrepancies
      between RCT abstracts and manuscripts. METHODS: A literature search of RCTs
      published in Spine, The Spine Journal, and Journal of Spinal Disorders and
      Techniques during a 10-year period (2001-2010) was performed. All manuscripts
      described as randomized trials concerning lumbar spinal surgery were selected.
      Manuscripts were analyzed using a standardized 21-item questionnaire to collect
      data regarding inconsistencies or bias in the abstract compared with the
      manuscript. Abstracts were considered deficient if they contained data that were
      either inconsistent with the manuscript or if they failed to include important
      findings from the manuscript. Four reviewers reported on the 40 manuscripts that
      met the inclusion criteria. Each manuscript was reviewed by 2 reviewers. In the
      event of conflicts in analysis, resolution was achieved through discussion
      between the reviewers. RESULTS: At least 1 inconsistency was found in 75% of
      studies. Despite the word "randomized" appearing in 75% of titles and 92.5% of
      abstracts, the method of randomization was not described in 37.5% of manuscripts
      and (if described) was considered unacceptable in 28%. The primary outcome of the
      study was clearly stated in only 22.5% of abstracts and 47.5% of manuscripts.
      Pertinent negatives were not reported in 40% of the abstracts. Relevant
      statistically significant results were reported in only 60% of abstracts.
      CONCLUSION: Abstracts are discrepant with full manuscripts in a surprisingly high
      proportion of manuscripts. Authors, editors, and peer reviewers should strive to
      ensure that abstracts accurately represent the data in RCT manuscripts.

PMID- 24583736
TI  - Cauda equina syndrome: assessing the readability and quality of patient
      information on the Internet.
AB  - STUDY DESIGN: A readability and quality control Internet-based study using
      recognized quality scoring systems. OBJECTIVE: To assess the readability and
      quality of Internet information relating to cauda equina syndrome accessed
      through common search engines. SUMMARY OF BACKGROUND DATA: Access to health
      related Internet information has increased dramatically during the past decade. A
      significant proportion of this information has been demonstrated to be set at too
      high a level for general comprehension. Despite this, searching for health
      related information is now the third most popular online activity. METHODS: A
      total of 125 cauda equina syndrome Web sites were analyzed from the 5 most
      popular Internet search engines: Google, Bing, Yahoo, Ask, and AOL. Web site
      authorship was classified: academic, physician, medico-legal, commercial, or
      discussion/social media. Readability of each Web site was assessed using the
      Flesch Reading Ease score, the Flesch-Kincaid grade level, and the Gunning Fog
      Index. Quality was calculated using the DISCERN instrument and The Journal of the
      American Medical Association benchmark criteria. The presence of HON-code
      certification was also assessed. RESULTS: Fifty-two individual Web sites were
      identified and assessed. The majority of Web sites were academic or physician
      compiled (53.8%; 28/52); however, a significant minority of Web sites were medico
      legal related (19.2%; 10/52). Just 13.5% (7/52) of Web sites were at or below the
      recommended sixth-grade readability level. HON-code certified Web sites achieved
      significantly greater DISCERN (P = 0.0006) and The Journal of the American
      Medical Association (P = 0.0002) scores. CONCLUSION: Internet information
      relating to cauda equina syndrome is of variable quality and largely set at an
      inappropriate readability level. Given this variability in quality, health care
      providers should direct patients to known sources of reliable, readable online
      information. Identification of reliable sources may be aided by known markers of
      quality such as HON-code certification.

PMID- 24583737
TI  - Trachea-thoracic vertebral body fistula causing spinal cord injury: a case
      report.
AB  - STUDY DESIGN: A case report and review of the literature. OBJECTIVE: To discuss
      the significance of identifying trachea-thoracic vertebral body fistula. SUMMARY
      OF BACKGROUND DATA: Several authors have reported the occurrence of communication
      between the trachea and the spinal canal or paraspinal abscess. However, trachea
      thoracic vertebral body fistulas have not been reported. METHODS: A 77-year-old
      male experienced gradually worsening lower-extremity palsy. Fifteen years before
      presentation, he had undergone retrosternal esophageal reconstruction with a
      gastric tube for esophageal cancer. RESULTS: Computed tomographic scan revealed
      compression of the Th5 vertebral body; the trachea and the Th5 vertebral body
      were connected by a fistula, and air seemed to enter Th5 from the trachea.
      Magnetic resonance image showed severe spinal canal stenosis. Posterior thoracic
      decompression and fusion was performed. Five months after the procedure, he
      regained the ability to walk with a cane, and computed tomographic scan revealed
      closure of the fistula and the bony fusion. CONCLUSION: To our knowledge, this is
      the first case report of a trachea-thoracic vertebral body fistula. Because the
      trachea is adjacent to the anterior aspect of the thoracic vertebrae, in cases of
      retrosternal esophageal reconstruction, trachea-vertebral body fistula should be
      a differential diagnosis for destructive changes in thoracic vertebrae without
      any signs of trauma.

PMID- 24583738
TI  - Association Between rs11190870 Polymorphism Near LBX1 and Susceptibility to
      Adolescent Idiopathic Scoliosis in East Asian Population: A Genetic Meta
      Analysis.
AB  - STUDY DESIGN: Meta-analysis to collect all the relevant studies to date to
      further investigate whether or not the rs11190870 polymorphism is associated with
      susceptibility to adolescent idiopathic scoliosis (AIS) in East Asian population.
      OBJECTIVE: To investigate whether or not the rs11190870 polymorphism is
      associated with susceptibility to AIS in East Asian population. SUMMARY OF
      BACKGROUND DATA: To date, the single nucleotide polymorphism rs11190870 was
      identified as the most significant common variant in Japanese females. Three
      association studies conducted in Chinese Han population from Hong Kong, Yangtze
      River region, and Southern region of mainland China replicated the association
      between AIS and rs1190870. However, there is limited published data about the
      association of rs11190870 with AIS in East Asian population. METHODS: A
      systematic search of all relevant studies published through August 2013 was
      conducted using the MEDLINE, EMBASE, OVID, and ScienceDirect. Single nucleotide
      polymorphism of rs11190870 was evaluated. The included studies were assessed in
      the analysis of the following allele model: T allele versus C allele for the
      allele-level comparison; (b) TC + TT versus CC for dominant model of T allele;
      (c) TT versus TC + CC for recessive model of T allele, and (d) TT versus CC for
      extreme genotype. RESULTS: Four studies with 8415 total participants (2889
      patients with AIS and 5526 controls), who were all East Asian population, were
      eligible for inclusion. We searched for genotypes T allele versus C allele, TT
      versus TC + CC, TC + TT versus CC, and TT versus CC in a fixed/random-effects
      model. The effect summary odds ratios and 95 % confidence intervals were
      obtained, which shows significant association between rs11190870 and AIS in East
      Asian populations (all genetic models P < 0.001). Subgroup analyses were
      conducted according to sex. The results showed a significant association between
      rs11190870 and AIS in female (all genetic models, P < 0.001) but not in male (all
      genetic models, P > 0.05). CONCLUSION: The present meta-analysis demonstrated
      that the T allele of single nucleotide polymorphism rs11190870 may be a major
      susceptibility locus in the East Asian population with AIS, especially in female.
      LEVEL OF EVIDENCE: 1.

PMID- 24583739
TI  - Survey of Cervical Spine Research Society members on the use of high-dose
      steroids for acute spinal cord injuries.
AB  - STUDY DESIGN: A questionnaire survey. OBJECTIVE: To characterize surgeons'
      current perspectives on the administration of methylprednisolone for acute spinal
      cord injury (SCI) and determine how this has changed during the last 7 years.
      SUMMARY OF BACKGROUND DATA: The determinants of and complications associated with
      off-label steroid use for acute SCI remain controversial. METHODS: A survey was
      sent to surgeon members of the Cervical Spine Research Society requesting
      information regarding their use of steroids for acute SCI. Determinants included
      surgeons' specialty, trauma center level, number of SCIs treated per year,
      severity of injury, and location of injury. These results were compared across
      groups as well as with a historical control. RESULTS: In the case of cervical
      complete and incomplete SCIs, 47.4% and 56.4% of respondents, respectively,
      reported using steroids. For complete and incomplete thoracolumbar spine
      injuries, the usage rate was 46.2% and 55.1%, respectively. There has been a
      significant (P < 0.0001) decrease in the number of surgeons using high-dose
      steroids in the treatment of acute SCIs when compared with a previous report in
      2006 (56% vs. 89%).More than 80% of respondents reported sepsis, active
      gastrointestinal bleeding, and SCI occurring earlier than 8 hours as
      contraindications. Seventy-one percent of respondents reported observing
      complications from the use of steroids, and 76.3% thought that the complications
      were severe enough to limit steroid use. Of the surgeons who used steroids for
      SCI, 26% thought that steroids improved neurological recovery, 19.2% used
      steroids to adhere to institutional protocol, and 25.6% stated they did not think
      steroids were beneficial but used them because of medicolegal concerns.
      CONCLUSION: There has been a significant decrease in the number of surgeons using
      high-dose steroids for acute SCIs. Sepsis, gastrointestinal bleeding, and an
      injury occurring more than 8 hours prior to presentation were agreed upon as
      contraindications to steroid use.

PMID- 24583741
TI  - 2013 ISSLS Presidential Address: Support From the World and Gifts to the World.

PMID- 24583740
TI  - Unknown Case: Part 2.

PMID- 24583742
TI  - Unknown case: part 1.

PMID- 24583743
TI  - Point of view.

PMID- 24583744
TI  - The basis of mechanical instability in degenerative disc disease: a cadaveric
      study of abnormal motion versus load distribution.
AB  - STUDY DESIGN: A biomechanical study in cadaveric lumbar spine. OBJECTIVE: To
      establish the basis of mechanical stability in degenerative disc disease from the
      relationship between range of motion (ROM), neutral zone motion (NZ), intradiscal
      pressure profile, and instantaneous axis or rotation (IAR) in advancing grades of
      disc degeneration. SUMMARY OF BACKGROUND DATA: The basis of mechanical
      instability in lumbar disc degeneration remains poorly understood. Controversy
      exists between abnormal motion and abnormal loading theories. METHODS: Thirty
      nine lumbar motion segments were graded for staging of disc degeneration with
      magnetic resonance scan. These specimens were tested for ROM and NZ in a 6 df
      spine simulator, with 7.5 N.m unconstrained, cyclical loading. Continuous
      tracking of IAR was derived from ROM data. Intradiscal pressure profiles were
      determined using needle-mounted pressure transducer, drawn across the disc space
      under constant loading. RESULTS: The ROM showed insignificant change, but a trend
      of increase from grade I through III and a decrease with advanced degeneration.
      NZ increased significantly with advancing disc degeneration. Intradiscal pressure
      profile showed an even distribution of the load in normal discs but a
      depressurized nucleus and irregular spikes of excessive loading, with advancing
      degeneration. The IAR showed a smooth excursion in normal versus irregular jerky
      excursion in degenerated discs, without significant change in excursion. The
      center of rotation, derived from IAR, showed significantly increased vertical
      translation with advancing degeneration, indicating an abnormal quality of
      motion. CONCLUSION: The study established a basis of mechanical instability in
      the lumbar spine with advancing disc degeneration as an abnormal quality of
      motion represented by variation in IAR and center of rotation, increased NZ
      motion without any increase in quantity of motion, and abnormal load distribution
      across the disc space with spikes of high load amidst depressurized nucleus. The
      study cannot identify clinical instability but finds an association between the
      abnormal motions and the abnormal load distribution in mechanical instability.
      LEVEL OF EVIDENCE: N/A.

PMID- 24583745
TI  - A prospective randomized controlled study of endoscopic sphincterotomy with the
      Endocut mode or conventional blended cut mode.
AB  - BACKGROUND: Although the potential advantages of the Endocut mode (E-mode) of
      endoscopic sphincterotomy (EST) over the conventional blended cut mode (C-mode)
      have been reported, the problems, including the small sample size and
      retrospective analysis, that occurred in previous studies make it difficult to
      conclude the advantage of the E-mode regarding the safety and efficacy. We
      performed a prospective randomized controlled study to compare these modes.
      METHODS: A total of 360 patients with choledocholithiasis or stenosis of the bile
      duct were randomly assigned to one of the modes. To avoid the technical bias due
      to multiple operators or institutions, the main operator and the institution were
      restricted to only one experienced doctor and 3 institutions at his place of
      employment, respectively. We defined pancreatitis, bleeding, and perforation as
      complications of EST. Besides, bleeding includes endoscopically evident bleeding
      that was defined as visible during the procedure of sphincterotomy and temporary
      slight oozing. RESULTS: The complications occurred in 20 (11.2%) patients from
      the E-mode group: pancreatitis in 6 (3.4%) and endoscopically evident bleeding in
      14 (7.8%). In contrast, the complications occurred in 25 (13.8%) patients from
      the C-mode group: pancreatitis in 7 (3.9%) and endoscopically evident bleeding in
      18 (9.9%), although these findings were not statistically significant. Overall,
      there were no severe complications. There were no significant differences in
      completion ratio of EST and the time taken for the sphincterotomy between both
      groups. CONCLUSIONS: The E-mode could not surpass the C-mode in safety and
      efficacy under the operation by a single endoscopist.

PMID- 24583746
TI  - Moderate to severe and prolonged left lower-abdominal pain is the best symptom
      characterizing symptomatic uncomplicated diverticular disease of the colon: a
      comparison with fecal calprotectin in clinical setting.
AB  - BACKGROUND: Left lower-abdominal pain is considered the best symptom to
      differentiate between symptomatic uncomplicated diverticular disease (SUDD) and
      irritable bowel syndrome (IBS). However, this statement has not been validated
      yet. GOALS: The aim of this study was to assess whether prolonged left lower
      quadrant pain is the best symptom characterizing SUDD and be able to
      differentiate SUDD from IBS-like symptoms in diverticulosis, and to compare the
      location of abdominal pain with fecal calprotectin (FC) expression. STUDY:
      Seventy-two patients suffering from abdominal pain and having diverticula at
      colonoscopy were enrolled. Patients were classified according to SUDD definition
      (abdominal pain for at least 24 consecutive hours in left lower abdomen) (42
      patients) and IBS-like symptoms fulfilling Rome III criteria (30 patients).
      Abdominal pain was assessed using a 10-point visual scale, assigning numerical
      values from 0 (absence of pain) to 10 (severe pain). FC expression was assessed
      by a rapid test in all patients enrolled. RESULTS: FC test was positive in 27
      (64.3%) patients in the SUDD group and in no patient in the IBS-like group
      (P<0.0001). In patients with SUDD, there was a significant correlation between
      the severity of the abdominal pain and the FC score (P=0.0015). Extension of
      diverticulosis correlated with FC score (P=0.022) and the severity of
      diverticulosis (P=0.005). CONCLUSIONS: Severe and prolonged left lower-abdominal
      pain seems to be the best symptom characterizing SUDD, and it can differentiate
      these patients from those harboring diverticula but suffering from IBS-like
      according to Rome III criteria.

PMID- 24583747
TI  - Naltrexone therapy for Crohn's disease and ulcerative colitis.

PMID- 24583748
TI  - Optic neuropathy, myelopathy, anemia, and neutropenia caused by acquired copper
      deficiency after gastric bypass surgery.
AB  - Malabsorptive bariatric surgery is rapidly becoming a major cause of copper
      deficiency given the increasing prevalence of these procedures for morbid
      obesity. Acquired copper deficiency can present with clinically significant
      hematologic and neurological manifestations. Although hematologic manifestations
      of copper deficiency are rapidly reversible, significant neurological improvement
      after copper supplementation therapy is unusual and many patients remain
      debilitated and may only experience, at best, stabilization of the neurological
      manifestations. Here we present a case of an undiagnosed copper deficiency
      several years after bariatric gastric bypass surgery, in a patient who
      concomitantly used zinc-containing denture cream for several years, associated
      with anemia, neutropenia, myelopathy, respiratory failure, and bilateral optic
      neuropathy, which caused major vision loss. This patient was also a heterozygote
      carrier of the 5,10-methylenetetrahydrofolate reductase A1298C gene polymorphism,
      which may affect copper metabolism. Intravenous copper repletion resulted in
      rapid correction of hematologic indices. However, neurological manifestations,
      including vision loss responded only modestly to copper supplementation, despite
      achieving normal blood copper concentrations. Clinicians should consider copper
      deficiency in patients at risk, as in this case, as a delayed diagnosis can lead
      to irreversible disability due to neurological manifestations. 

PMID- 24583749
TI  - The correlation between manometric and videofluoroscopic measurements of the
      swallowing function in brainstem stroke patients with Dysphagia.
AB  - GOALS: The objective of the current study was to examine the correlation between
      high-resolution manometric and videofluoroscopic measurements of the swallowing
      function. BACKGROUND: In such cases in which manometric analysis is not feasible,
      it would be ideal if information regarding pressure during swallowing could be
      inferred from a videofluoroscopic swallowing study (VFSS) evaluation alone.
      STUDY: The swallowing function was examined using simultaneous VFSS and high
      resolution manometry (HRM) in 24 brainstem stroke survivors with dysphagia. The
      pharyngeal constriction ratio (PCR) and upper esophageal sphincter (UES) maximum
      opening diameter were measured using VFSS digital analysis. The pharyngeal
      maximum pressure and UES residual pressure were measured using HRM. The
      correlation coefficients between the PCR and pharyngeal maximum pressure and
      between the UES maximum opening diameter and UES residual pressure were
      calculated. The Spearman analyses were used to calculate the correlation
      coefficients between manometric and fluoroscopic parameters. RESULTS: The
      increase in the pharyngeal maximum pressure wave amplitude was significantly
      correlated with a decrease in the PCR (r=-0.849, P<0.001). The increase in the
      UES opening diameter was significantly correlated with a decrease in the UES
      residual pressure (r=-0.705, P<0.001). High space-time correlations between the
      pressure and kinematics of swallowing-related structures were obtained using
      simultaneous manometric and videofluoroscopic measurements. CONCLUSIONS: Certain
      VFSS measures are significantly correlated with measures of pressure assessed
      using HRM. The measures may be used as indicators of possible pressure deficits
      of swallowing.

PMID- 24583750
TI  - A laboratory score in the diagnosis of autoimmune atrophic gastritis: a
      prospective study.
AB  - BACKGROUND: Several biomarkers have been proposed for the diagnosis of autoimmune
      atrophic gastritis (AAG), but at the present there is no appropriate testing
      strategy for the disease. GOALS: The aim of this study was to develop and
      validate a laboratory score able to address the diagnosis of AAG in a general
      practice setting. STUDY: We prospectively evaluated a number of serum biomarkers
      (vitamin B12, mean corpuscular volume, hemoglobin, gastrin, and chromogranin A
      levels) in a case-control population and built 2 biochemical scores, the first
      with all the parameters [Global Score (GS)], and the second as the best
      statistical combination of them [Simple Score (SS)]. In the second phase we
      validated the score that proved to be more efficient on a random population
      referred to our center (Gastroenterology Outpatient Clinic). RESULTS: Both models
      turned out to be reliable in detecting patients with suspected AAG, showing
      excellent accuracy [area under the receiver operating curve (AUC-ROC) 0.94; 95%
      confidence interval (CI), 0.91-0.97 for GS and AUC-ROC 0.93; 95% CI, 0.89-0.86
      for SS]. The SS proved to be more convenient because of its accessibility and
      availability in a general setting and its low cost. The validation of the SS
      showed a sensitivity of 85.7% (95% CI, 57.2-98.2) and a specificity of 83.7% (95%
      CI, 74.2-90.89). CONCLUSIONS: Herein, we describe 2 nonexpensive and reliable
      score models, particularly the SS, that can be applied in daily medical practice
      for identifying patients potentially affected by AAG.

PMID- 24583751
TI  - Development and validation of a risk stratification-based screening model for
      predicting colorectal advanced neoplasia in Korea.
AB  - GOALS: To develop and validate a risk stratification-based screening model for
      predicting colorectal advanced neoplasia in Korea. BACKGROUND: Colorectal
      advanced neoplasia is the relevant finding of screening colonoscopy. Risk
      estimation for advanced neoplasia may be helpful to improve compliance and to
      develop more cost-effective approaches toward screening. STUDY: We developed
      Korean Colorectal Screening (KCS) score by optimizing and adjusting Asia-Pacific
      Colorectal Screening (APCS) score to predict advanced neoplasia in an
      asymptomatic Korean population who received screening colonoscopies from
      September 2006 to September 2009. Moreover, we validated the KCS score in another
      Korean cohort who received screening colonoscopies from October 2009 to February
      2011. We also assessed the predictive power and diagnostic performance of both
      KCS and APCS scores. RESULTS: There were 3561 subjects in the derivation cohort
      and 1316 subjects in the validation cohort, with a prevalence of advanced
      neoplasia of 4.7% and 4.3%, respectively. After a multivariate analysis, KCS was
      developed as 0 to 8 points comprising of age, sex, body mass index, smoking, and
      family history of CRC. Using KCS scores to stratify the validation cohort, the
      prevalences of advanced neoplasia in the 3 risk tiers (average, moderate, and
      high) were 2.0%, 3.7%, and 10.9%, respectively. Moderate-risk and high-risk tiers
      showed 2.1- and 6.5-fold increased prevalences, respectively, of advanced
      neoplasia compared with average risk tier. In addition, KCS score showed
      relatively good discriminative power (ROC=0.681) and higher sensitivity compared
      with APCS score for the high-risk tier. CONCLUSIONS: KCS score may be clinically
      simple and useful for assessing advanced neoplasia risk in Korea. However, racial
      disparity should be considered in risk stratification-based screening in each
      country.

PMID- 24583752
TI  - A computer system to be used with laser-based endoscopy for quantitative
      diagnosis of early gastric cancer.
AB  - GOALS: To evaluate the usefulness of a newly devised computer system for use with
      laser-based endoscopy in differentiating between early gastric cancer, reddened
      lesions, and surrounding tissue. BACKGROUND: Narrow-band imaging based on laser
      light illumination has come into recent use. We devised a support vector machine
      (SVM)-based analysis system to be used with the newly devised endoscopy system to
      quantitatively identify gastric cancer on images obtained by magnifying endoscopy
      with blue-laser imaging (BLI). We evaluated the usefulness of the computer system
      in combination with the new endoscopy system. STUDY: We evaluated the system as
      applied to 100 consecutive early gastric cancers in 95 patients examined by BLI
      magnification at Hiroshima University Hospital. We produced a set of images from
      the 100 early gastric cancers; 40 flat or slightly depressed, small, reddened
      lesions; and surrounding tissues, and we attempted to identify gastric cancer,
      reddened lesions, and surrounding tissue quantitatively. RESULTS: The average SVM
      output value was 0.846 +/- 0.220 for cancerous lesions, 0.381 +/- 0.349 for
      reddened lesions, and 0.219 +/- 0.277 for surrounding tissue, with the SVM output
      value for cancerous lesions being significantly greater than that for reddened
      lesions or surrounding tissue. The average SVM output value for differentiated
      type cancer was 0.840 +/- 0.207 and for undifferentiated-type cancer was 0.865 +/
      0.259. CONCLUSIONS: Although further development is needed, we conclude that our
      computer-based analysis system used with BLI will identify gastric cancers
      quantitatively.

PMID- 24583753
TI  - Therapeutic management of chronic hepatitis B in clinical practice: a region-wide
      survey.
AB  - GOALS: To characterize the clinical and treatment pattern in a large population
      of hepatitis B virus (HBV) patients managed at tertiary referral centers in
      clinical practice. BACKGROUND: Successful treatment, either with interferon (IFN)
      or nucleos(t)ide analogs (NUCs), of chronic HBV infection is associated with
      improved long-term patient outcome. However, in clinical practice, the actual
      management of these patients is not well characterized, and data regarding
      treatment pattern in this setting are lacking. METHODS: In this cross-sectional
      study, we evaluated 505 patients chronically infected with HBV alone and who had
      at least 1-year follow-up. We assessed indication to, rate of, and type of
      treatment as well as the characteristics of treated patients. RESULTS: Overall
      prevalence of positivity for HBe antigen was 19.3%, and the majority of patients
      had chronic hepatitis (47.5%). Non-Italian patients represented approximately one
      third of the population (27.1%). Among patients with indication to antiviral
      therapy (n=318), treatment was actually carried out in 264 patients (83.0%),
      prevalently with NUCs (65.9%). IFN-treated patients were younger (P<0.001), more
      frequently male (P=0.025) and HBeAg positive (P=0.003), and less frequently
      cirrhotics (P<0.001) as compared with patients treated with NUCs. CONCLUSIONS: In
      a geographical area with a low positivity for HBe antigen, antiviral therapy is
      actually carried out in the majority of patients who have indication to
      treatment, prevalently with NUCs, whereas IFN treatment is more frequently
      carried out in young, HBe antigen-positive patients who do not have advanced
      liver disease.

PMID- 24583754
TI  - Titers of anti-tissue transglutaminase antibody correlate well with severity of
      villous abnormalities in celiac disease.
AB  - GOALS: We reviewed our celiac disease (CeD) database to study if anti-tissue
      transglutaminase (tTG) antibody (ab) titers correlate with severity of villous
      abnormalities in Indian patients and to find out a cutoff value of anti-tTG ab
      fold-rise, which could best predict CeD. BACKGROUND: Guidelines for diagnosing
      CeD suggest that biopsy could be avoided in some patients with high anti-tTG ab
      titer. STUDY: We reviewed a cohort of 366 anti-tTG ab-positive individuals in
      whom duodenal biopsies were performed. Anti-tTG ab was obtained before initiation
      of gluten-free diet. Anti-tTG ab results were expressed in terms of fold-rise by
      calculating ratio of observed values with cutoff value. CeD was diagnosed if in
      addition to positive serology, patients had villous atrophy (>Marsh grade 2) and
      unequivocal response to gluten-free diet. RESULTS: The mean anti-tTG fold-rise in
      groups with Marsh grade <=2 was 2.6 (+/-2.5), grade 3a was 4.0 (+/-3.9), 3b was
      5.7 (+/-5.1), and 3c was 11.8 (+/-8.0). The positive likelihood ratio for
      diagnosing CeD was 15.4 and 27.4 at 12- and 14-fold-rise of anti-tTG ab titer,
      respectively. The positive predictive value of diagnosis of CeD was 100% when
      anti-tTG ab titer was 14-fold higher over the cutoff value. Fifty-seven (43.9%)
      individuals with anti-tTG titer rise <2-fold high also had CeD. CONCLUSIONS: As
      severity of villous abnormality increases, titer of anti-tTG also rises. Presence
      of villous atrophy can be predicted at very high anti-tTG ab titer. In contrast
      to emerging belief, mucosal biopsies should be performed even if anti-tTG ab
      titer is <2 times, because many patients with CeD have low titers.

PMID- 24583755
TI  - Biography of Marvin E. Ament, MD.

PMID- 24583756
TI  - Yield of screening colonoscopy in first-degree relatives of patients with
      serrated polyposis syndrome.
AB  - GOALS: We aimed to evaluate the diagnostic yield of screening colonoscopies in
      first-degree relatives (FDRs) of patients with serrated polyposis syndrome (SPS).
      BACKGROUND: Patients with SPS are at an increased risk for colorectal cancer.
      Although inheritance patterns are unknown, FDRs of these patients have an
      increased risk for both colorectal cancer and SPS. Prospective studies evaluating
      the yield of screening colonoscopies in this group are however scarce. This
      information would be useful to evaluate a possible mode of inheritance and to
      investigate whether screening colonoscopies are justified in this group. STUDY:
      FDR of patients with SPS were invited to undergo colonoscopy. The diagnostic
      yield was expressed by the number of FDRs with at least 1 significant polyp
      relative to the total number of included FDRs. Significant polyps were defined
      adenomas, traditional serrated adenomas, sessile serrated adenoma/polyp, or
      proximal hyperplastic polyp. Tissue specimens were reviewed by one expert
      pathologist. RESULTS: Seventy-seven FDRs underwent colonoscopy (median age 52 y;
      interquartile range, 41 to 60). Colorectal cancer was not diagnosed. One or more
      significant polyps were detected in 43% of FDRs. No differences based on age,
      gender, or familial relationship were observed in the detection of polyps. Seven
      first-degree (9%) relatives had multiple polyps (>=5). Eleven (14%) FDRs
      fulfilled SPS WHO-criterion 2, of whom 1 sibling also met SPS WHO-criterion 3.
      CONCLUSIONS: The yield of a single screening colonoscopy in FDRs of patients with
      serrated polyposis is substantial, warranting a colonoscopy screening program for
      these individuals.

PMID- 24583758
TI  - Does H. pylori eradication therapy benefit patients with hepatic encephalopathy?:
      systematic review.
AB  - BACKGROUND: Ammonia is considered to play a central role in the pathogenesis of
      (minimal) hepatic encephalopathy ((M)HE). Bacterial urease activity is the
      regulatory enzyme, and bacteria colonizing the colon were originally assumed to
      be the main source of urease activity. Current concepts of the pathogenesis of
      (M)HE focus, among other things, on ammonia, which is generated both by urease
      activity of intestinal bacteria and by Helicobacter pylori in the stomach. AIM: :
      The aim of this study was to provide a systematic review of the role of H. pylori
      in the pathogenesis of HE. METHODS: A systematic review was conducted following
      the recommendations in the Preferred Reporting Items for Systematic reviews and
      Meta-Analysis (PRISMA) statement with a database search in PubMed, Scopus, and
      the Cochrane Database for all original contributions published from January 1950
      to December 2013. As search terms in title and abstract, the following
      combinations were used: hepatic encephalopathy AND Helicobacter pylori, HE AND
      Helicobacter pylori, MHE AND Helicobacter pylori, hyperammonemia AND Helicobacter
      pylori, and minimal hepatic encephalopathy AND Helicobacter pylori, with a
      language restriction to English and German. RESULTS: Observational studies
      revealed conflicting results concerning a possible role of H. pylori infection in
      the pathogenesis of HE. Thirteen prospective clinical trials assessed the effect
      of H. pylori eradication in patients with HE and liver cirrhosis. Seven of these
      showed a beneficial effect of eradication therapy on (M)HE. All of these studies
      were highly diverse in design and methodology. CONCLUSIONS: Eradication therapy
      in H. pylori-positive cirrhotic patients may have a beneficial influence on
      hyperammonemia and (M)HE, but evidence from well-designed clinical studies is
      weak.

PMID- 24583760
TI  - Changing community health service delivery in economically less-developed rural
      areas in China: impact on service use and satisfaction.
AB  - OBJECTIVE: To evaluate the impact of a model of rural community health service
      (CHS) on the use and acceptability of primary healthcare services. DESIGN: Quasi
      experimental. SETTING: Two adjacent rural counties in China. PARTICIPANTS: 5842
      residents in 2009 and 3807 in 2010 from 980 households in 7 intervention
      townships and 49 villages; 2232 residents in 2009 and 2315 in 2010 from 628
      households in 3 comparison townships and 9 villages. All residents were
      approached to participate, with no significant differences in age or sex between
      groups. INTERVENTION: Multilevel intervention in 2009 including training rural
      practitioners, encouraging clinic improvements, providing clinical guidelines,
      standards and subsidies. DATA COLLECTION: Surveys of community members from
      randomly sampled households in 2009 and 2010. PRIMARY OUTCOME MEASURES:
      Satisfaction with and utilisation of outpatient and public health services.
      ANALYSIS: Factor analysis confirmed two components of satisfaction. Univariate
      and multilevel analysis was used. RESULTS: Satisfaction scores for intervention
      county respondents increased from 21.4 (95% CI 21.1 to 21.7) to 22.1 (95% CI 21.7
      to 22.4) with no change in comparison area. In multilevel analysis, satisfaction
      with patient-centred care was associated with chronic disease, shorter waiting
      times and county. Satisfaction with clinic environment and cost was associated
      with female gender, shorter waiting times but not county. The proportion of
      children receiving immunisation in intervention village clinics increased from
      42.5% (95% CI 27.9% to 47.1%) to 59.2% (95% CI 53.8% to 64.6%) whereas this
      decreased in comparison villages (16.5%; 95% CI 10.3% to 22.7% to 6.0%; 95% CI
      1.3% to 10.7%). Antenatal visits increased in intervention villages (from 69.0%,
      95% CI 65.8% to 73.1% to 75.8%, 95% CI 72.2% to 79.4%) with no change in
      comparison villages. CONCLUSIONS: Introduction of a CHS model adapted to
      economically less-developed rural areas was associated with some improvements in
      satisfaction with care and use of some village-based public health services.
      Further research is needed to determine its public health impact and application
      to other areas.

PMID- 24583757
TI  - Double-blind randomized placebo-controlled clinical trial of omega 3 fatty acids
      for the treatment of diabetic patients with nonalcoholic steatohepatitis.
AB  - BACKGROUND: Nonalcoholic steatohepatitis (NASH) is common and severe in patients
      with diabetes mellitus. Although, there are no effective treatments for NASH in
      diabetic patients, preliminary reports suggest that polyunsaturated fatty acids
      (PUFA) may be beneficial in these patients. AIM: A prospective, randomized,
      double-blind placebo-controlled study (NCT 00323414) was performed in NASH
      patients with diabetes. Clinicaltrials.gov (NCT 00323414). SUBJECTS AND METHODS:
      A total of 37 patients (50.6 +/- 9.8 y) with well-controlled diabetes
      (HbA1C<8.5%) were randomized to receive either PUFA containing eicosapentaenoic
      acid (2160 mg) and docosahexaenoic acid (1440 mg) daily or an isocaloric,
      identical placebo containing corn oil for 48 weeks under CONSORT guidelines.
      Clinical, demographics, biochemical laboratory tests, body composition using
      DEXA, and liver biopsy were performed at randomization and at the end of
      treatment. Liver biopsy was scored by the NASH CRN criteria. An intention-to
      treat analysis was performed. RESULTS: At inclusion, sex, age, body weight,
      biochemical tests, glucose control, and liver histology were similar in the 2
      treatment groups. There was no change in liver enzymes, body weight, or body
      composition during the study in either group. At the end of the treatment,
      hepatic steatosis and the activity score improved (P<0.05) and lobular
      inflammation worsened (P<0.001) with placebo but was unchanged with PUFA. At the
      end of the treatment, insulin resistance (serum glucose and HOMA) worsened with
      PUFA but not placebo. CONCLUSIONS: PUFA provided no benefit over placebo in NASH
      patients with diabetes. The effects of PUFA on histology and insulin resistance
      were inferior to placebo. These data provide no support for PUFA supplements in
      NASH.

PMID- 24583761
TI  - Scientific publications in respiratory journals from Chinese authors in various
      parts of North Asia: a 10-year survey of literature.
AB  - OBJECTIVES: Respiratory disease remains one of the leading causes of morbidity
      and mortality in China. However, little is known about the research status of
      respirology in three major regions of China-Mainland (ML), Hong Kong (HK) and
      Taiwan (TW). A 10-year survey of literature was conducted to compare the three
      regions' outputs in the research of respirology. DESIGN: A bibliometric study.
      SETTING: China. PARTICIPANTS AND OUTCOME MEASURES: A literature search in PubMed
      database, updated as of September 2012, led to the identification of the related
      articles from 2000 to 2009. The number of total articles, randomised controlled
      trials, case reports, meta-analysis, impact factors (IF), citations and articles
      published in top general medicine journals was collected for quantity and quality
      comparisons. RESULTS: 2208 articles were collected, 814 from ML, 909 from TW and
      485 from HK. The total number of articles from the three regions has increased
      significantly from 2000 to 2009. The number of articles published per year from
      ML has exceeded that from HK in 2005 and TW in 2008. The accumulated IF of
      articles from TW (3192.417) was much higher than that from ML (2409.956) and HK
      (1898.312). HK got the highest average IF of respirology articles and the
      majority of articles were published in top general medicine journals.
      CONCLUSIONS: The total number of published articles from the three major regions
      of China has increased notably from 2000 to 2009. The annual number of
      publications by ML researchers exceeded those from TW and HK. However, the
      quality of articles from TW and HK is better than that from ML.

PMID- 24583759
TI  - The association of the 'additional height index' with atopic diseases, non-atopic
      asthma, ischaemic heart disease and mortality: a population-based study.
AB  - OBJECTIVE: Intrauterine growth has been associated with atopic conditions. Growth
      and adult height have been associated with cardiovascular disease, cancers and
      mortality but are highly genetic traits. The objectives of the study were as
      follows: first, to define a height measure indicating an individual's height
      below or above that which could be expected based on parental height (genetic
      inheritance) and growth charts. It was named 'the additional height index' (AHI),
      defined as (attained-expected) height; second, to investigate possible
      associations of AHI with atopic versus non-atopic health outcomes and with
      ischaemic heart disease (IHD) and IHD mortality. DESIGN: General population-based
      study. SETTING: Research centre. PARTICIPANTS: A random sample of 2656 men and
      women living in greater Copenhagen took part in the MONICA10 study (the Danish
      monitoring trends and determinants of cardiovascular disease). In total, 1900
      participants with information of parental height were selected. OUTCOME MEASURES:
      Atopic sensitisation (serum IgE), questionnaire information of atopic dermatitis,
      rhinoconjunctivitis, asthma or wheezing, and registry-based diagnoses of IHD/IHD
      mortality from National Registries. RESULTS: Increasing levels of AHI were
      inversely associated with non-atopic asthma, non-atopic wheezing, IHD and IHD
      mortality (IHD-all). For one SD increase of AHI, the OR or HR with CI in adjusted
      analyses was non-atopic asthma OR=0.52 (0.36 to 0.74), non-atopic wheezing
      OR=0.67 (0.51 to 0.89), and IHD-all HR=0.89 (0.78 to 1.01). The level of AHI was
      higher among individuals with atopic dermatitis, allergic rhinoconjunctivitis and
      atopic sensitisation (all p values <0.001) compared with individuals without
      those conditions; however, the associations were not confirmed in adjusted
      analyses. CONCLUSIONS: Individuals with childhood conditions that led them to
      attain tallness higher than expected from their parents' height may be at lower
      risk of non-atopic asthma/wheeze and IHD/IHD mortality but possibly at higher
      risk of atopic conditions. The measure of tallness below or above the expected
      height could be a sensitive alternative to normal height in epidemiological
      analyses.

PMID- 24583762
TI  - A longitudinal, multicentre, cohort study of community rehabilitation service
      delivery in long-term neurological conditions.
AB  - OBJECTIVES: Part A: To pilot the use of a register to identify and monitor
      patients with complex needs arising from long-term neurological conditions. Part
      B: To determine the extent to which patients' needs for health and social
      services are met following discharge to the community after inpatient
      rehabilitation; to identify which factors predict unmet needs and to explore the
      relationship between service provision and outcomes at 12 months. DESIGN: A
      multicentre, prospective, cohort study surveying participants at 1, 6 and 12
      months using postal/online questionnaires and telephone interview. SETTING:
      Consecutive discharges to the community from all nine tertiary, specialist,
      inpatient neurorehabilitation services in London over 18 months in 2010-2011.
      PARTICIPANTS: Of 576 admissions 428 patients were recruited at discharge: 256
      responded at 4 weeks, 212 at 6 months and 190 at 12 months. MEASURES:
      Neurological Impairment Scale, The Needs and Provision Complexity Scale, The
      Northwick Park Dependency Scale, Community Integration Questionnaire, Zarit
      Burden Inventory. RESULTS: n=322 (75%) expressed willingness to be registered,
      but in practice less than half responded to questionnaires at 6 and 12 months
      (49% and 44%, respectively), despite extensive efforts to contact them, with no
      significant differences between responders and non-responders. Significant unmet
      needs were identified within the first year following discharge, particularly in
      rehabilitation, social work support and provision of specialist equipment.
      Dependency for basic care and motor and cognitive impairment predicted services
      received, together accounting for 40% of the variance. Contra to expectation,
      patients whose rehabilitation needs were met were more dependent and less well
      integrated at 12 months post discharge than those with unmet needs. CONCLUSIONS:
      Registration is acceptable to most patients, but questionnaires/telephone
      interviews may not be the most efficient way to reach them. When community
      resources are limited, service provision tends to be focused on the most
      dependent patients. REGISTRATION: The study was registered with the NIHR
      Comprehensive Local Research Network: ID number 7503.

PMID- 24583764
TI  - Physiology in perspective: the burden of obesity.

PMID- 24583763
TI  - beta-cell function after weight-loss induced by bariatric surgery.

PMID- 24583765
TI  - If body fatness is under physiological regulation, then how come we have an
      obesity epidemic?
AB  - Life involves a continuous use of energy, but food intake, which supplies that
      energy, is episodic. Feeding is switched on and off by a complex array of
      predominantly gut-derived peptides (and potentially nutrients) that initiate and
      terminate feeding bouts. Energy is stored as glucose and glycogen to overcome the
      problem of the episodic nature of intake compared with the continuous demand.
      Intake is also adjusted to meet immediate changes in demands. Most animals also
      store energy as fat. In some cases, this serves the purpose of storing energy in
      anticipation of a known future shortfall (e.g., hibernation, migration, or
      reproduction). Other animals, however, store fat in the absence of such
      anticipated needs, and in this case the fat appears to be stored in preparation
      for unpredictable catastrophic shortfalls in supply. Fat storage, however, brings
      disadvantages as well as advantages, in particular an increased risk of
      predation. Hence, many animals seem to have evolved a dual intervention point
      system preventing them from storing too little or too much fat. The physiological
      basis of the lower intervention point is well established, but the upper
      intervention point is much less studied. Human obesity can potentially be
      understood in an evolutionary context as due to drift in the upper intervention
      point following release from predation 2 million years ago (the drifty gene
      hypothesis) combined with a stimulus in modern society to overconsume calories,
      possibly attempting to satisfy intake of a limiting micro- or macro-nutrient like
      protein (the protein leverage hypothesis).

PMID- 24583767
TI  - GLP-1-based strategies: a physiological analysis of differential mode of action.
AB  - DPP4 inhibitors and GLP-1 receptor agonists used in incretin-based strategies
      treat Type 2 diabetes with different modes of action. The pharmacological blood
      GLP-1R agonist concentration targets pancreatic and some extrapancreatic GLP-1R,
      whereas DPP4i favors the physiological activation of the gut-brain-periphery axis
      that could allow clinicians to adapt the management of Type 2 diabetes, according
      to the patient's pathophysiological characteristics.

PMID- 24583766
TI  - AMPK: regulating energy balance at the cellular and whole body levels.
AB  - AMP-activated protein kinase appears to have evolved in single-celled eukaryotes
      as an adenine nucleotide sensor that maintains energy homeostasis at the cellular
      level. However, during evolution of more complex multicellular organisms, the
      system has adapted to interact with hormones so that it also plays a key role in
      balancing energy intake and expenditure at the whole body level.

PMID- 24583768
TI  - Sex differences in the developmental origins of cardiovascular disease.
AB  - The Developmental Origins of Health and Disease (DOHaD) proposes that adverse
      events during early life program an increased risk for cardiovascular disease.
      Experimental models provide proof of concept but also indicate that insults
      during early life program sex differences in adult blood pressure and
      cardiovascular risk. This review will highlight the potential mechanisms that
      contribute to the etiology of sex differences in the developmental programming of
      cardiovascular disease.

PMID- 24583769
TI  - Neural mechanisms of cardioprotection.
AB  - This review highlights the importance of neural mechanisms capable of protecting
      the heart against lethal ischemia/reperfusion injury. Increased parasympathetic
      (vagal) activity limits myocardial infarction, and recent data suggest that
      activation of autonomic reflex pathways contributes to powerful innate mechanisms
      of cardioprotection underlying the remote ischemic conditioning phenomena.

PMID- 24583771
TI  - A monoclonal antibody targeting neuropilin-1 inhibits adhesion of MCF7 breast
      cancer cells to fibronectin by suppressing the FAK/p130cas signaling pathway.
AB  - Neuropilin-1 (NRP-1) is a nontyrosine kinase coreceptor for semaphorin 3A and the
      vascular endothelial growth factor involved in tumor angiogenesis, growth, and
      metastasis and is regarded as a promising target for cancer therapy. In the
      present study, we investigated the effects of an anti-NRP-1 monoclonal antibody
      (mAb) that we generated for MCF7 breast cancer cellular adhesion studies. MTT,
      colony formation, and adhesion assays showed that our anti-NRP-1 mAb dose
      dependently inhibited MCF7 proliferation and fibronectin adhesion, leading to a
      rounded cellular morphology. Further, rhodamine phalloidin stain revealed that
      fibronectin-dependent formation of actin stress fibers was inhibited by anti-NRP
      1 mAb. Immunoprecipitation and western blot showed that anti-NRP-1 mAb treatment
      inhibited the formation of NRP-1-alpha5beta1 integrin complexes and suppressed
      the phosphorylation of focal adhesion kinase and p130cas in MCF7 cells. These
      findings contribute to further understanding the NRP-1 function in cell adhesion
      and tumor metastasis. Moreover, our anti-NRP-1 mAb is a prospective drug
      candidate for tumor treatment. 

PMID- 24583772
TI  - Effect of cholesterol on behavior of 5-fluorouracil (5-FU) in a DMPC lipid
      bilayer, a molecular dynamics study.
AB  - In this work, molecular dynamics (MD) simulations were performed to investigate
      the effects of cholesterol on the interaction between the hydrophilic anticancer
      drug, 5-FU, and fully hydrated 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC)
      bilayer. Several structural and dynamical parameters of DMPC bilayers with
      varying amounts of cholesterol (0, 25, and 50mol%) in the presence and absence of
      drug molecules were calculated. Moreover, the free energy barriers for
      translocation of one 5-FU molecule from water to the lipid bilayer were
      determined by using the potential of mean force (PMF). PMF studies indicated that
      the location of the maximum free energy barrier was in the hydrophobic middle
      region of bilayer, while the minimums of the barrier were located at the
      hydrophilic part of bilayer at the interface with water. The minimum and maximum
      of the free energy profiles were independent of cholesterol concentration and
      suggested that the drug molecules 5-FU were accumulated in the vicinity of the
      polar head group of lipid bilayers. Moreover, the results showed that with
      increasing cholesterol concentration in the bilayer, the free energy barrier for
      translocation of 5-FU across the bilayer also increases which can be attributed
      to the condensing effect of the cholesterol on the bilayer. 

PMID- 24583770
TI  - Phosphodiesterases maintain signaling fidelity via compartmentalization of cyclic
      nucleotides.
AB  - Novel technological advances have improved our understanding of how cyclic
      nucleotides are able to convey signals faithfully between cellular compartments.
      Phosphodiesterases play a crucial role in shaping these signals in health and
      disease. The concept of compartmentalization is guiding the search for therapies
      that have the potential to offer greater efficacy and tolerability compared with
      current treatments.

PMID- 24583774
TI  - Abstracts of the 2014 SGI 61st Annual Scientific Meeting, March 26-29, 2014,
      Florence Italy.

PMID- 24583773
TI  - Routine real-time cost-effectiveness monitoring of a web-based depression
      intervention: a risk-sharing proposal.
AB  - BACKGROUND: A new health care technology must be cost-effective in order to be
      adopted. If evidence regarding cost-effectiveness is uncertain, then the decision
      maker faces two choices: (1) adopt the technology and run the risk that it is
      less effective in actual practice, or (2) reject the technology and risk that
      potential health is forgone. A new depression eHealth service was found to be
      cost-effective in a previously published study. The results, however, were
      unreliable because it was based on a pilot clinical trial. A conservative
      decision maker would normally require stronger evidence for the intervention to
      be implemented. OBJECTIVE: Our objective was to evaluate how to facilitate
      service implementation by shifting the burden of risk due to uncertainty to the
      service provider and ensure that the intervention remains cost-effective during
      routine use. METHODS: We propose a risk-sharing scheme, where the service cost
      depends on the actual effectiveness of the service in real-life setting. Routine
      efficacy data can be used as the input to the cost-effectiveness model, which
      employs a mapping function to translate a depression specific score into quality
      adjusted life-years. The latter is the denominator in the cost-effectiveness
      ratio calculation, required by the health care decision maker. The output of the
      model is a "value graph", showing intervention value as a function of its
      observed (future) efficacy, using the ?30,000 per quality-adjusted life-year
      (QALY) threshold. RESULTS: We found that the eHealth service should improve the
      patient's outcome by at least 11.9 points on the Beck Depression Inventory scale
      in order for the cost-effectiveness ratio to remain below the ?30,000/QALY
      threshold. The value of a single point improvement was found to be between ?200
      and ?700, depending on depression severity at treatment start. Value of the
      eHealth service, based on the current efficacy estimates, is ?1900, which is
      significantly above its estimated cost (?200). CONCLUSIONS: The eHealth
      depression service is particularly suited to routine monitoring, since data can
      be gathered through the Internet within the service communication channels. This
      enables real-time cost-effectiveness evaluation and allows a value-based price to
      be established. We propose a novel pricing scheme where the price is set to a
      point in the interval between cost and value, which provides an economic surplus
      to both the payer and the provider. Such a business model will assure that a
      portion of the surplus is retained by the payer and not completely appropriated
      by the private provider. If the eHealth service were to turn out less effective
      than originally anticipated, then the price would be lowered in order to achieve
      the cost-effectiveness threshold and this risk of financial loss would be borne
      by the provider.

PMID- 24583775
TI  - 4-Amino-pyrrolopyridine-5-carboxamide: a novel scaffold for JAK1-selective
      inhibitors.
AB  - Despite a high level of interest in selective Janus kinase 1 (JAK1) inhibitors
      and their potential for the treatment of inflammatory diseases such as rheumatoid
      arthritis (RA), only a few such inhibitors have been reported to date. In this
      study, a novel 4-amino-1H-pyrrolo[2,3-b]pyridine-5-carboxamide scaffold was
      designed through structural modification of the potent JAK1-selective inhibitor,
      C2-methyl imidazopyrrolopyridine. Among the series studied, the 4-(2
      aminoethyl)amino-pyrrolopyridine derivative, 2j, exhibited a significant 24.7
      fold JAK1/JAK2 selectivity along with reasonable inhibitory activity against JAK1
      (IC50=2.2 uM). The noticeable JAK1-selectivity of 2j was then tackled through a
      molecular docking study, which showed that the aminoethyl functionality of 2j is
      well positioned to discriminate the subtle but significant difference in the size
      of the ligand binding sites between JAK1 and JAK2.

PMID- 24583776
TI  - A planar Schiff base platinum(II) complex: crystal structure, cytotoxicity and
      interaction with DNA.
AB  - A new platinum(II) complex of salphen derivative, namely Schiff base ligand that
      derived from o-phenylenediamine and 5-chlorosalicylaldehyde was synthesized. The
      complex possessed a planar mononuclear structure. The in vitro cytotoxicities of
      the complex were evaluated by microculture tetrozolium (MTT) assay against seven
      human tumor cell lines with the IC50 values of ca. 11.61 uM. Cell cycle analysis
      indicated that the complex induced apoptosis and G1-phase arrest in A549 cells.
      The results of colony formation assay showed that the complex could suppress the
      proliferation and viability of A549 cells. The binding of the complex to
      potential target DNA were investigated by fluorescence spectroscopy, viscosity
      measurements, fluorescence polarization and agarose gel electrophoresis. The
      results suggest that the most probable binding mode of the complex is
      intercalation. 

PMID- 24583777
TI  - Monte Carlo simulations on atropisomerism of thienotriazolodiazepines applicable
      to slow transition phenomena using potential energy surfaces by ab initio
      molecular orbital calculations.
AB  - Compounds with a medium-sized flexible ring often show atropisomerism that is
      caused by the high-energy barriers between long-lived conformers that can be
      isolated and often have different biological properties to each other. In this
      study, the frequency of the transition between the two stable conformers, aS and
      aR, of thienotriazolodiazepine compounds with flexible 7-membered rings was
      estimated computationally by Monte Carlo (MC) simulations and validated
      experimentally by NMR experiments. To estimate the energy barriers for
      transitions as precisely as possible, the potential energy (PE) surfaces used in
      the MC simulations were calculated by molecular orbital (MO) methods. To
      accomplish the MC simulations with the MO-based PE surfaces in a practical
      central processing unit (CPU) time, the MO-based PE of each conformer was pre
      calculated and stored before the MC simulations, and then only referred to during
      the MC simulations. The activation energies for transitions calculated by the MC
      simulations agreed well with the experimental DeltaG determined by the NMR
      experiments. The analysis of the transition trajectories of the MC simulations
      revealed that the transition occurred not only through the transition states, but
      also through many different transition paths. Our computational methods gave us
      quantitative estimates of atropisomerism of the thienotriazolodiazepine compounds
      in a practical period of time, and the method could be applicable for other slow
      dynamics phenomena that cannot be investigated by other atomistic simulations. 

PMID- 24583778
TI  - A study on the adsorption of heavy metals by using raw wheat bran bioadsorbent in
      aqueous solution phase.
AB  - Raw wheat bran (R-WB) was used as a biomass adsorbent. The properties of R-WB
      were investigated. Moreover, the adsorption of cadmium and lead ions onto R-WB
      was evaluated. Adsorption equilibrium of cadmium and lead ions onto R-WB was
      achieved within 10 h, indicating that the adsorption followed a pseudo-second
      order model rather than a pseudo-first-order kinetic model. The adsorption amount
      increased with increasing temperature. Correlation coefficient of the Langmuir
      equation is 0.999 for cadmium and 0.996 for lead ions, and that of the Freundlich
      equation is 0.994 for cadmium and 0.993 for lead ions. The negative DeltaG value
      implied that the adsorption of cadmium and lead ions onto R-WB is a spontaneous
      process. The positive DeltaS value indicated an increase in randomness at the
      solid-liquid interface. The optimal conditions for the adsorption column
      experiment were investigated (space velocity (SV) 2.2 1/h, linear velocity (LV)
      0.1 m/h for cadmium; SV 6.51 1/h, LV 0.23 m/h for lead ions). Further, repeated
      adsorption-desorption of the cadmium and lead ions could be effected by using
      0.01 mol/L HCl or 0.01 mol/L HNO3 solution. Consequently, polluted water could be
      successfully purified by using a column filled with this bioadsorbent.

PMID- 24583779
TI  - Diarylamines incorporating hexahydrophenalene or octahydrobenzoheptalene as
      retinoid X receptor (RXR)-specific agonists.
AB  - Selective ligands for retinoic acid receptors (RARs) and for retinoid X receptors
      (RXRs) are required for both biological studies and therapeutic purposes. We have
      synthesized a series of diarylamines incorporating hexahydrophenalene or
      octahydrobenzoheptalene as a hydrophobic moiety and examined their activities
      towards RARs and RXRs. Most of these compounds showed agonistic activity towards
      RXRs, but were inactive towards RARs. These RXR-specific ligands showed
      synergistic activity in RARalpha,beta ligand-induced terminal differentiation of
      leukemia cell line HL-60. 

PMID- 24583780
TI  - Cytotoxic activity and DNA-binding properties of isoeuxanthone derivatives.
AB  - In this study, the interactions of different groups substituted isoeuxanthone
      derivatives with calf thymus DNA (ct DNA) were investigated by spectrophotometric
      methods and viscosity measurements. Results indicated that the xanthone
      derivatives could intercalate into the DNA base pairs by the plane of xanthone
      ring and the various substituents may influence the binding affinity with DNA
      according to the calculated quenching constant values. Furthermore, two tumor
      cell lines including the human cervical cancer cell line (HeLa) and human
      hepatocellular liver carcinoma cell line (HepG2) were used to evaluate the
      cytotoxic activities of xanthone derivatives by acid phosphatase assay. Analyses
      showed that the oxiranylmethoxy substituted xanthone exhibited more effective
      cytotoxic activity against the cancer cells than the other substituted xanthones.
      The effects on the inhibition of tumor cells in vitro agreed with the studies of
      DNA-binding. 

PMID- 24583781
TI  - New cassane-type diterpenoids of Caesalpinia echinata (Leguminosae) exhibiting NF
      kappaB inhibitory activities.
AB  - Seven new cassane-type diterpenoids, echinalides A-G (1-7), were isolated from
      the stem of Caesalpinia echinata LAM. (Leguminosae). The structures were
      established on the basis of their chemical properties and spectroscopic evidence,
      including two dimensional (2D)-NMR analysis. These compounds were assessed for
      inhibitory activity against nuclear factor kappaB (NF-kappaB). Echinalides C and
      D, in particular, significantly inhibited NF-kappaB-responsive reporter gene
      expression at 5.0 uM, an effect almost equivalent to that of parthenolide, a
      known potent inhibitor of NF-kappaB. 

PMID- 24583782
TI  - Efficient delivery and distribution in skin of chlorogenic acid and resveratrol
      induced by microemulsion using sucrose laurate.
AB  - To achieve efficient skin delivery of polyphenols, we prepared a novel oil-in
      water (o/w)-type microemulsion (MESL) using sucrose laurate as a surfactant and
      ethanol, isopropyl myristate and water as other components. We examined its
      usefulness by in vitro studies on skin delivery of chlorogenic acid and
      resveratrol as hydrophilic and hydrophobic polyphenols using Yucatan micropig
      skin, and also examined the difference in the distribution of these polyphenols
      in skin. MESL significantly improved skin incorporation of these polyphenols at
      all time points examined (6, 20, 40 h) in the epidermis and at 20 and 40 h in the
      dermis, compared with the microemulsion using Tween 80 as a surfactant component
      (MEK), although the solubilization capacity of MESL was lower than that of MEK.
      Using MESL, the incorporation amount in the dermis of each polyphenol increased
      with time, while the amount in the epidermis was almost constant during the time
      examined. Incorporation efficiencies into skin of chlorogenic acid and
      resveratrol induced by MESL at 40 h after application were about 6-fold and 19
      fold higher in the epidermis and 3.5-fold and 15-fold higher in the dermis,
      respectively, than those by MEK. The increase was more prominent for resveratrol.
      Hydrophilic chlorogenic acid was distributed slightly more in the epidermis,
      while hydrophobic and smaller-molecular-weight resveratrol was mainly distributed
      in the dermis. These findings suggest that MESL could be a promising vehicle for
      the efficient skin delivery of chlorogenic acid and resveratrol, especially for
      resveratrol to the dermis. 

PMID- 24583783
TI  - Effect of the compaction platform on the densification parameters of tableting
      excipients with different deformation mechanisms.
AB  - Several compaction models have been attempted to explain the compression and
      compaction phenomena of excipients. However, the resulting parameters could be
      influenced by the compaction platform such as dwell time, compact mass, geometry
      and type of material. The goal of this study is to assess the effect of these
      variables on the densification parameters obtained from key models such as
      Heckel, non-linear Heckel, Kawakita, Carstensen, and Leuenberger. The
      relationship among the parameters derived was determined by employing a Principal
      Component Analysis. Results indicated that factors such as compact geometry,
      consolidation time and compact mass had a negligible impact on parameters such as
      tensile strength, yield pressure and compressibility. On the contrary, the
      excipient type had the largest influence on these parameters. Further, the
      Leuenberger (gamma) and Carstensen (f) parameters were highly correlated and
      related to the excipient deformation mechanism. Sorbitol and PVP-k30 were the
      most highly compactable excipients and were characterized for having a low yield
      pressure (P(y)), compressibility (a), and critical porosity (epsilon(c)). The
      magnitude of these parameters was highly dependent on the consolidation behavior
      of each material.

PMID- 24583785
TI  - Two new ring-contracted congeners of rhizopodin illustrate significance of the
      ring moiety of macrolide toxins on the actin disassembly-mediated cytotoxicity.
AB  - Two new cytotoxic dilactones, bisisorhizopodin (1) and isorhizopodin (2),
      together with known divalent actin depolymerizer rhizopodin (3), were isolated
      from the culture broth of a myxobacterium Myxococcus stipitatus. Spectroscopic
      analyses established that 1 and 2 are doubly and singly acyl-migrated isomers of
      3, respectively, and comparison of their cytotoxicity revealed gradual decrease
      in the activity as the size of the ring contracted. Because the side chains of
      macrolide toxins uniformly block the contact between the actin protomers, the
      present result demonstrates substantial contribution of structurally diverse
      rings to the affinity of macrolide toxins for its target protein. 

PMID- 24583784
TI  - Three new lignan glycosides with IL-6 inhibitory activity from Akebia quinata.
AB  - Three new lignan glycosides, akeqintoside A [(7S,8S)-7,8-dihydro-8-hydroxymethyl
      7-(4-hydroxy-3-methoxyphenyl)-1'-benzofuranpropanol 2'-O-beta-D-glucopyranoside]
      (1), akeqintoside B [(7R,8R)-7,8-dihydro-8-hydroxymethyl-7-(4-hydroxy-3
      methoxyphenyl)-1'-(9'-methoxy-7'-propenyl) benzofuran 2'-O-beta-D
      glucopyranoside] (2), and akequintoside C [7R*,8R*-dihydroxy-7-(4-hydroxy-3
      methoxyphenyl)-glycerol 9-O-beta-D-(6'-O-caffeoyl)-glucopyranoside] (3) were
      isolated from Akebia quinata along with five known compounds, syringin (4),
      vanilloloside (5), salidroside (6), 3,4-dihydroxyphenylethyl alcohol 8-O-beta-D
      glucopyranoside (7), and calceolarioside B (8). The structures of the compounds
      were identified based on one dimensional (1D)- and 2D-NMR, including (1)H-(1)H
      correlation spectroscopy (COSY), heteronuclear single quantum coherence (HSQC),
      heteronuclear multiple bond connectivity (HMBC) and nuclear Overhauser effect
      spectroscopy (NOESY) spectroscopic analyses. The inhibitory activity of these
      isolated compounds against interleukin-6 (IL-6) production in tumor necrosis
      factor-alpha (TNF-alpha) stimulated MG-63 cells was also examined. 

PMID- 24583786
TI  - Design and synthesis of 2-nitroimidazoles with variable alkylating and acylating
      functionality.
AB  - The synthesis of a small series of 2-nitroimidazoles in which the beta-amino
      alcohol side chain was amidated with a range of alkylating/acylating
      functionality is described. Synthetic methodologies were developed that generally
      provided for selective N-acyl versus N,O-bisacyl products. In vitro, target
      analogs showed minimal radiosensitization activity, with only a few exhibiting a
      sensitizer enhancement ratio (SER) >2.0 and C(1.6) values comparable to reference
      agents RB-6145 and RSU-1069. In an assay to determine potential to alkylate
      biomolecules, representative analogs showed <1% of the alkylating activity of RSU
      1069. In vivo, one analog showed an enhancement ratio of 1.6 relative to vehicle
      control when tested in B6C3F1 mice with an implanted KHT sarcoma. The data
      reinforce prior findings that there is a correlation between alkylation potential
      and in vivo activity.

PMID- 24583787
TI  - Development and evaluation of a new immunohistochemistry-based test for the
      detection of rabies virus neutralizing antibodies.
AB  - Rabies claims about 55,000 human lives and many hundreds of thousands of
      livestock every year, worldwide. Despite a heavy disease burden, laboratory
      facilities to diagnose the infection remain scarce in most countries of the
      developing world where the disease is endemic. Rapid Fluorescent Focus Inhibition
      Test (RFFIT) and Fluorescent Antibody Virus Neutralization Test (FAVN) are the
      common tests done in the rabies diagnostic laboratories to detect and quantitate
      Rabies Virus Neutralizing Antibodies (RVNA). RFFIT is most often employed in
      confirming seroconversion following prophylactic vaccination, and to aid ante
      mortem diagnosis in suspected cases of rabies. Though this remains one of the
      most sought-after diagnostic services in rabies laboratories, the requirements
      for expensive anti-rabies fluorochrome antibody conjugate and a fluorescent
      microscope restrict its performance to only a few reference laboratories. Cost
      effective laboratory diagnostic methods employing affordable technology are a
      need of the hour in the rabies-endemic countries. In this study we have developed
      a new immunohistochemistry-based neutralization test and extensively evaluated it
      along with RFFIT. One hundred and 20 human serum samples collected after post
      exposure vaccination were subjected to both the tests for determining RVNA
      titers. The results obtained with the new test correlated significantly with
      those of RFFIT. Further validation of the inter- and intra- assay precision,
      lower limit of quantification (LLOQ) and specificity was also performed. The best
      correlation between the 2 methods, however, was observed only when the RVNA
      concentrations in the samples were>20 IU/mL. Overall, the immunohistrochemistry
      based neutralization test yielded satisfactory results. We suggest that it might
      serve as a cost-effective alternative to RFFIT in low-resource settings in the
      developing countries.

PMID- 24583790
TI  - Chemical contaminants in drinking water: where do we go from here?

PMID- 24583789
TI  - The effectiveness of an Internet support forum for carers of people with
      dementia: a pre-post cohort study.
AB  - BACKGROUND: The well-being of informal carers of people with dementia is an
      important public health issue. Caring for an elderly relative with dementia may
      be burdensome and stressful, and can negatively affect the carer's social,
      family, and professional life. The combination of loss, the physical demands of
      caregiving, prolonged distress, and biological vulnerabilities of older carers
      may compromise their physical health, increase social isolation, and increase the
      risk of anxiety and depressive disorders. Caregiver stress is also linked to
      negative outcomes for the recipient of care and costs to society, including
      increased nursing home and hospital admissions. Consequently, carer support
      interventions are an important component of dementia care. Computer-mediated
      carer support offers a range of potential advantages compared to traditional face
      to-face support groups, including accessibility and the possibility of tailoring
      to meet individual needs, but there has been little research on its effectiveness
      so far. OBJECTIVE: This mixed-methods study examined the impact of a well
      respected UK-based online support forum for carers of people with dementia.
      METHODS: A total of 61 new forum users completed measures of anxiety (7-item
      Generalized Anxiety Disorder scale, GAD-7), depression (9-item Patient Health
      Questionnaire, PHQ-9), and quality of relationship with the person with dementia
      (Scale for the Quality of the Current Relationship in Caregiving, SQCRC), at
      baseline and again after 12 weeks of forum usage, within a pre-post design. In
      addition, 8 participants were interviewed about their experiences with using the
      forum. RESULTS: There was an improvement in the quality of the relationship with
      the person with dementia (SQCRC: P=.003). There was no change in users'
      depression (PHQ-9) or anxiety (GAD-7) over the 12-week study period. Interview
      participants reported a range of positive experiences and benefits from using the
      forum. Limited negative experiences were also reported. CONCLUSIONS: Many of the
      reported experiences and benefits are unique to online peer support. Further
      research into online peer support for carers of people with dementia is needed to
      clarify who benefits under what conditions.

PMID- 24583788
TI  - Serum microRNA expression patterns that predict early treatment failure in
      prostate cancer patients.
AB  - We aimed to identify microRNA (miRNA) expression patterns in the serum of
      prostate cancer (CaP) patients that predict the risk of early treatment failure
      following radical prostatectomy (RP). Microarray and Q-RT-PCR analyses identified
      43 miRNAs as differentiating disease stages within 14 prostate cell lines and
      reflectedpublically available patient data. 34 of these miRNA were detectable in
      the serum of CaP patients. Association with time to biochemical progression was
      examined in a cohort of CaP patients following RP. A greater than two-fold
      increase in hazard of biochemical progression associated with altered expression
      of miR-103, miR-125b and miR-222 (p<.0008) in the serum of CaP patients.
      Prediction models based on penalized regression analyses showed that the levels
      of the miRNAs and PSA together were better at detecting false positives than
      models without miRNAs, for similar level of sensitivity. Analyses of publically
      available data revealed significant and reciprocal relationships between changes
      in CpG methylation and miRNA expression patterns suggesting a role for CpG
      methylation to regulate miRNA. Exploratory validation supported roles for miR-222
      and miR-125b to predict progression risk in CaP. The current study established
      that expression patterns of serum-detectable miRNAs taken at the time of RP are
      prognostic for men who are at risk of experiencing subsequent early biochemical
      progression. These non-invasive approaches could be used to augment treatment
      decisions. 

PMID- 24583791
TI  - Severity and pattern of post-traumatic intervertebral disc degeneration depend on
      the type of injury.
AB  - BACKGROUND CONTEXT: The burst fracture of a vertebra is the result of a complex
      loading procedure and is often associated with intervertebral disc (IVD)
      degeneration. Likewise, the presumed etiologies are (i) the structural
      perturbation of the IVD/end plate, (ii) the impact of loading energy alone, and
      (iii) the depressurization of the nucleus pulposus. PURPOSE: To describe the
      pathogenesis of post-traumatic disc degeneration (DD) by comparing the severity
      and patterns of degeneration with different injury models. STUDY DESIGN: New data
      from an in vitro organ culture study are compared with the previous work on the
      same model system. METHODS: To investigate in detail the contribution of each
      factor (i-iii) to DD, we extended our previous work to compare three different
      segmental trauma processes in a rabbit full-organ in vitro model: burst fracture
      (Group A, etiologies i-iii), equienergetic loading without a fracture (Group B,
      ii), and endplate puncturing (Group C, iii). DD markers (apoptosis, necrosis,
      matrix remodeling, inflammation) were monitored up to 28 days posttrauma. Gene
      transcription data were subjected to principal component analysis and
      agglomerative hierarchical clustering to identify and compare pathologic
      patterns. RESULTS: Only Group A showed the full profile of DD: reduced
      glycosaminoglycan content, increased caspase-3/7 and lactate dehydrogenase (LDH)
      activity, and elevated messenger RNA of catabolic (matrix metalloproteinase-1, 
      3, -13) and proinflammatory (tumor necrosis factor-alpha, interleukin [IL]-6, IL
      8, and monocyte chemotactic protein-1) genes. In Group B, only catabolic and
      proinflammatory genes were slightly upregulated. In Group C, LDH but not caspase
      3/7 activity was increased. Catabolic and proinflammatory genes were upregulated,
      although less compared with Group A. Principal component analysis revealed
      different transcription patterns for Group C. CONCLUSIONS: The structural
      perturbation of the end plate/IVD, but not the loading energy or nuclear
      depressurization, promotes DD. In addition, end-plate puncturing triggers a
      different pathogenesis, consistent with a more continuous matrix remodeling
      process.

PMID- 24583792
TI  - Phase I dendritic cell p53 peptide vaccine for head and neck cancer.
AB  - BACKGROUND: p53 accumulation in head and neck squamous cell carcinoma (HNSCC)
      cells creates a targetable tumor antigen. Adjuvant dendritic cell (DC)-based
      vaccination against p53 was tested in a phase I clinical trial. EXPERIMENTAL
      METHODS: Monocyte-derived DC from 16 patients were loaded with two modified HLA
      class I p53 peptides (Arm 1), additional Th tetanus toxoid peptide (Arm 2), or
      additional Th wild-type (wt) p53-specific peptide (Arm 3). Vaccine DCs (vDC) were
      delivered to inguinal lymph nodes at three time points. vDC phenotype,
      circulating p53-specific T cells, and regulatory T cells (Treg) were serially
      monitored by flow cytometry and cytokine production by Luminex. vDC properties
      were compared with those of DC1 generated with an alternative maturation regimen.
      RESULTS: No grade II-IV adverse events were observed. Two-year disease-free
      survival of 88% was favorable. p53-specific T-cell frequencies were increased
      postvaccination in 11 of 16 patients (69%), with IFN-gamma secretion detected in
      four of 16 patients. Treg frequencies were consistently decreased (P = 0.006)
      relative to prevaccination values. The phenotype and function of DC1 were
      improved relative to vDC. CONCLUSION: Adjuvant p53-specific vaccination of
      patients with HNSCC was safe and associated with promising clinical outcome,
      decreased Treg levels, and modest vaccine-specific immunity. HNSCC patients' DC
      required stronger maturation stimuli to reverse immune suppression and improve
      vaccine efficacy.

PMID- 24583794
TI  - Estrogen receptor mutations in breast cancer--new focus on an old target.
AB  - Recent studies have provided strong evidence for the emergence of substantial
      numbers of constitutively active ESR1 mutations in estrogen receptor-positive
      metastatic breast cancer that are undetected in primary disease. Some of these
      mutants remain partially sensitive to current anti-estrogen therapies but
      effective therapeutics targeted at them may require new approaches.

PMID- 24583793
TI  - Increased KIT inhibition enhances therapeutic efficacy in gastrointestinal
      stromal tumor.
AB  - PURPOSE: Gastrointestinal stromal tumor (GIST) is the most common human sarcoma
      and a model of targeted molecular therapy. GIST depends on oncogenic KIT
      signaling and responds to the tyrosine kinase inhibitor imatinib. However,
      imatinib is rarely curative. We hypothesized that PLX3397, which inhibits KIT and
      colony-stimulating-factor-1 receptor (CSF1R), would be more efficacious than
      imatinib in GIST by also depleting tumor-associated macrophages, which are
      generally thought to support tumor growth. EXPERIMENTAL DESIGN: We treated
      Kit(V558del/+) mice that develop GIST or mice with subcutaneous human GIST
      xenografts with imatinib or PLX3397 and analyzed tumor weight, cellular
      composition, histology, molecular signaling, and fibrosis. In vitro assays on
      human GIST cell lines were also performed. RESULTS: PLX3397 was more effective
      than imatinib in reducing tumor weight and cellularity in both Kit(V558del)(/+)
      murine GIST and human GIST xenografts. The superiority of PLX3397 did not depend
      on depletion of tumor-associated macrophages, because adding CSF1R inhibition did
      not improve the effects of imatinib. Instead, PLX3397 was a more potent KIT
      inhibitor than imatinib in vitro. PLX3397 therapy also induced substantial
      intratumoral fibrosis, which impaired the subsequent delivery of small molecules.
      CONCLUSIONS: PLX3397 therapy has greater efficacy than imatinib in preclinical
      GIST models and warrants study in patients with GIST. The resultant intratumoral
      fibrosis may represent one of the barriers to achieving complete tumor
      eradication.

PMID- 24583795
TI  - Preclinical and early clinical evaluation of the oral AKT inhibitor, MK-2206, for
      the treatment of acute myelogenous leukemia.
AB  - PURPOSE: Recent studies suggested that AKT activation might confer poor prognosis
      in acute myelogenous leukemia (AML), providing the rationale for therapeutic
      targeting of this signaling pathway. We, therefore, explored the preclinical and
      clinical anti-AML activity of an oral AKT inhibitor, MK-2206. Experimental
      Methods: We first studied the effects of MK-2206 in human AML cell lines and
      primary AML specimens in vitro. Subsequently, we conducted a phase II trial of MK
      2206 (200 mg weekly) in adults requiring second salvage therapy for
      relapsed/refractory AML, and assessed target inhibition via reverse phase protein
      array (RPPA). RESULTS: In preclinical studies, MK-2206 dose-dependently inhibited
      growth and induced apoptosis in AML cell lines and primary AML blasts. We then
      treated 19 patients with MK-2206 but, among 18 evaluable participants, observed
      only 1 (95% confidence interval, 0%-17%) response (complete remission with
      incomplete platelet count recovery), leading to early study termination. The most
      common grade 3/4 drug-related toxicity was a pruritic rash in 6 of 18 patients.
      Nevertheless, despite the use of MK-2206 at maximum tolerated doses, RPPA
      analyses indicated only modest decreases in Ser473 AKT (median 28%; range, 12%
      45%) and limited inhibition of downstream targets. CONCLUSIONS: Although
      preclinical activity of MK-2206 can be demonstrated, this inhibitor has
      insufficient clinical antileukemia activity when given alone at tolerated doses,
      and alternative approaches to block AKT signaling should be explored.

PMID- 24583796
TI  - Dabrafenib and trametinib, alone and in combination for BRAF-mutant metastatic
      melanoma.
AB  - Dabrafenib and trametinib were approved for use as monotherapies in BRAF-mutant
      metastatic melanoma by the U.S. Food and Drug Administration (FDA) in 2013, and
      most recently, their use in combination has received accelerated FDA approval.
      Both drugs target the mitogen-activated protein kinase (MAPK) pathway: dabrafenib
      selectively inhibits mutant BRAF that constitutively activates the pathway, and
      trametinib selectively inhibits MEK1 and MEK2 proteins activated by RAF kinases.
      The phase III study of dabrafenib in BRAF(V600E) metastatic melanoma reported
      rapid tumor regression in most patients and a 59% objective RECIST response rate.
      The median progression-free survival (PFS) and overall survival (OS) were
      improved compared with dacarbazine. Toxicities were well tolerated and different
      from those reported for vemurafenib, the first FDA-approved BRAF inhibitor.
      Efficacy has been demonstrated in other BRAF-mutant genotypes. The phase III
      study of trametinib in BRAF inhibitor-naive patients with BRAF(V600E) or
      BRAF(V600K) also showed benefit with a prolonged median PFS and OS compared with
      chemotherapy. Trametinib is ineffective in patients who have progressed on BRAF
      inhibitors. A phase II trial of combined dabrafenib and trametinib demonstrated
      higher response rates and longer median PFS than dabrafenib monotherapy, with
      less cutaneous toxicity. Here, we review the clinical development of both drugs
      as monotherapies and in combination, and discuss their role in the management of
      BRAF-mutant melanoma.

PMID- 24583798
TI  - Phase I safety, pharmacokinetic, and pharmacodynamic study of SAR245409 (XL765),
      a novel, orally administered PI3K/mTOR inhibitor in patients with advanced solid
      tumors.
AB  - PURPOSE: This phase I, first-in-human study evaluated the safety, maximum
      tolerated dose (MTD), pharmacokinetics, pharmacodynamics, and preliminary
      efficacy of SAR245409, an inhibitor of pan-Class I phosphoinositide 3-kinase
      (PI3K) and mTOR, administered orally once or twice daily in patients with
      advanced solid tumors. EXPERIMENTAL DESIGN: Eighty-three patients received
      SAR245409. Doses ranged from 15 to 120 mg twice daily, and 70 to 100 mg once
      daily. A 3+3 dose-escalation design was used to determine the MTD. Patients were
      evaluated for adverse events and response. Assessments included pharmacokinetic,
      pharmacodynamic impact of SAR245409 on PI3K pathway signaling in hair sheath
      cells, skin and tumor, and characterization of tumor molecular alterations.
      RESULTS: The MTDs were 50 mg twice daily and 90 mg once daily. The most frequent
      treatment-related adverse events were nausea (36.1%), diarrhea (21.7%), vomiting
      (19.3%), and decreased appetite (16.9%). The most frequent treatment-related
      grade 3/4 adverse events were increases in alanine aminotransferase (6.0%) and
      aspartate aminotransferase (4.8%). SAR245409 had a relatively short plasma half
      life (2.96-7.52 hours). At MTDs, once- and twice-daily regimens yielded similar
      mean steady-state plasma exposure. A reduction in PI3K and mTORC1/mTORC2 pathway
      signaling was observed in serial hair sheath cells, skin, and tumor samples. Best
      response was stable disease in 48% of evaluable patients; seven patients had
      minor tumor regression. Twelve patients with stable disease were treated for >=16
      weeks. No trend was observed correlating tumor molecular alteration with
      antitumor activity. CONCLUSION: SAR245409 had a manageable safety profile,
      demonstrated reduced PI3K and mTORC1/mTORC2 pathway signaling and was associated
      with clinically relevant stable disease.

PMID- 24583797
TI  - Prevalence and clinical implications of epstein-barr virus infection in de novo
      diffuse large B-cell lymphoma in Western countries.
AB  - PURPOSE: Epstein-Barr virus-positive (EBV(+)) diffuse large B-cell lymphoma
      (DLBCL) of the elderly is a variant of DLBCL with worse outcome that occurs most
      often in East-Asian countries and is uncommon in the Western hemisphere. We
      studied the largest cohort of EBV(+) DLBCL, independent of age, treated with
      rituximab combined with CHOP (R-CHOP) in developed Western countries.
      EXPERIMENTAL DESIGN: A large cohort (n = 732) of patients with DLBCL treated with
      R-CHOP chemotherapy is included from the multicenter consortium. This study group
      has been studied for expression of different biomarkers by immunohistochemistry,
      genetic abnormalities by FISH and mutation analysis, genomic information by gene
      expression profiling (GEP), and gene set enrichment analysis (GSEA). RESULTS:
      Twenty-eight patients (4.0%) were positive for EBV with a median age of 60.5
      years. No clinical characteristics distinguished patients with EBV(+) DLBCL from
      patients with EBV-negative (EBV(-)) DLBCL. Genetic aberrations were rarely seen.
      NF-kappaB p50, phosphorylated STAT-3, and CD30 were more commonly expressed in
      EBV(+) DLBCLs (P < 0.05). Significant differences in survival were not observed
      in patients with EBV(+) DLBCL versus EBV(-) DLBCL. However, CD30 expression
      combined with EBV conferred an inferior outcome. GEP showed a unique expression
      signature in EBV(+) DLBCL. GSEA revealed enhanced activity of the NF-kappaB and
      JAK/STAT pathways independent of molecular subtype. CONCLUSIONS: The clinical
      characteristics of patients with EBV(+) versus EBV(-) DLBCL are similar and EBV
      infection does not predict a worse outcome. EBV(+) DLBCL, however, has a unique
      genetic signature. CD30 expression is more common in EBV(+) DLBCL and, consistent
      CD30 and EBV is associated with an adverse outcome. Clin Cancer Res; 20(9); 2338
      49. (c)2014 AACR.

PMID- 24583799
TI  - CTLA4 blockade broadens the peripheral T-cell receptor repertoire.
AB  - PURPOSE: To evaluate the immunomodulatory effects of cytotoxic T-lymphocyte
      associated protein 4 (CTLA4) blockade with tremelimumab in peripheral blood
      mononuclear cells (PBMC). EXPERIMENTAL DESIGN: We used next-generation sequencing
      to study the complementarity-determining region 3 (CDR3) from the rearranged T
      cell receptor (TCR) variable beta (V-beta) in PBMCs of 21 patients, at baseline
      and 30 to 60 days after receiving tremelimumab. RESULTS: After receiving
      tremelimumab, there was a median of 30% increase in unique productive sequences
      of TCR V-beta CDR3 in 19 out of 21 patients, and a median decrease of 30% in only
      2 out of 21 patients. These changes were significant for richness (P = 0.01) and
      for Shannon index diversity (P = 0.04). In comparison, serially collected PBMCs
      from four healthy donors did not show a significant change in TCR V-beta CDR3
      diversity over 1 year. There was a significant difference in the total unique
      productive TCR V-beta CDR3 sequences between patients experiencing toxicity with
      tremelimumab compared with patients without toxicity (P = 0.05). No relevant
      differences were noted between clinical responders and nonresponders.
      CONCLUSIONS: CTLA4 blockade with tremelimumab diversifies the peripheral T-cell
      pool, representing a pharmacodynamic effect of how this class of antibodies
      modulates the human immune system.

PMID- 24583800
TI  - Molecular pathways: molecular basis for sensitivity and resistance to JAK kinase
      inhibitors.
AB  - Janus-activated kinases (JAK) are the mediators of a variety of cytokine signals
      via their cognate receptors that result in activation of intracellular signaling
      pathways. Alterations in JAK1, JAK2, JAK3, and TYK2 signaling contribute to
      different disease states, and dysregulated JAK-STAT signaling is associated with
      hematologic malignancies, autoimmune disorders, and immune-deficient conditions.
      Genetic alterations of JAK2 occur in the majority of patients with
      myeloproliferative neoplasms and occur in a subset of patients with acute
      leukemias. JAK-mediated signaling critically relies on STAT transcription
      factors, and on activation of the MAPK and PI3K/Akt signaling axes. Hyperactive
      JAK at the apex of these potent oncogenic signaling pathways therefore represents
      an important target for small-molecule kinase inhibitors in different disease
      states. The JAK1/2 inhibitor ruxolitinib and the JAK3 inhibitor tofacitinib were
      recently approved for the treatment of myelofibrosis and rheumatoid arthritis,
      respectively, and additional ATP-competitive JAK inhibitors are in clinical
      development. Although these agents show clinical activity, the ability of these
      JAK inhibitors to induce clinical/molecular remissions in hematologic
      malignancies seems limited and resistance upon chronic drug exposure is seen.
      Alternative modes of targeting JAK2 such as allosteric kinase inhibition or HSP90
      inhibition are under evaluation, as is the use of histone deacetylase inhibitors.
      Combination therapy approaches integrating inhibition of STAT, PI3K/Akt, and MAPK
      pathways with JAK kinase inhibitors might be critical to overcome malignancies
      characterized by dysregulated JAK signaling.

PMID- 24583801
TI  - Is there clinical value to prognostic signatures in early-stage NSCLC?
AB  - pAMPK and pmTOR favorably predicted outcome in early non-small cell lung cancer
      (NSCLC). The differences were small. Phosphoprotein lability makes routine
      clinical use and validation difficult. Protein immunohistochemistry is unlikely
      to be clinically useful, and numerous efforts to create predictive models to
      select resected patients for therapy have been unsuccessful.

PMID- 24583802
TI  - New approaches but the same flaws in the search for prognostic signatures.
AB  - A six-gene prognostic colorectal cancer hypoxia score was generated from
      expression data from in vitro experiments and microarray datasets and was
      validated in two distinct patient cohorts. The approach followed by the authors
      is original and biologically sound but could be limited by potential biases and
      other methodologic limitations.

PMID- 24583803
TI  - Highly stable sub-5 nm Sn6O4(OH)4 nanocrystals with ultrahigh activity as
      advanced photocatalytic materials for photodegradation of methyl orange.
AB  - Among numerous active photocatalytic materials, Sn-based oxide nanomaterials are
      promising photocatalytic materials in environmental protection measures such as
      water remediation due to their excellent physicochemical property. Research on
      photocatalytic nanomaterials for photodegradation of methyl orange (MO) so far
      has focused on TiO2-based nanostructures; e.g., TiO2-P25 is recognized to be the
      best commercial photocatalyst to date, rather than Sn-based oxide nanomaterials,
      in spite of their impressive acid- and alkali-resistant properties and high
      stability. Here, we demonstrate very high photocatalytic activity of highly
      stable sub-5 nm hydromarchite (Sn6O4(OH)4) nanocrystals synthesized by a simple
      and environmentally friendly laser-based technique. These Sn6O4(OH)4 nanocrystals
      exhibit ultrahigh photocatalytic performance for photodegradation of MO and their
      degradation efficiency is far superior to that of TiO2-P25. The detailed
      investigations demonstrated that the great photocatalytic activity results from
      the ultrafine size and unique surface activity induced by the laser-based
      technique. Mass production of reactive species of hydroxyl radicals was detected
      in the experiments due to the appropriate bandgap of Sn6O4(OH)4 nanocrystals.
      These findings actually open a door to applications of Sn-based oxide
      nanomaterials as advanced photocatalytic materials.

PMID- 24583804
TI  - Baby with the bath water: response to Fanniff and Letourneau.
AB  - Fanniff and Letourneau concluded that neither their review of the published
      literature nor their own investigation supported the use of Scale 1 of the
      Juvenile Sex Offender Assessment Protocol-II (J-SOAP-II). I argue that empirical
      findings on Scale 1 are mixed and that there is more support in the literature
      than one might conclude from reading Fanniff and Letourneau. Their negative
      conclusions about Scale 1 are based on a flawed literature review as well as
      problematic methods in their own investigation. 

PMID- 24583805
TI  - A flocking based method for brain tractography.
AB  - We propose a new method to estimate axonal fiber pathways from Multiple Intra
      Voxel Diffusion Orientations. Our method uses the multiple local orientation
      information for leading stochastic walks of particles. These stochastic particles
      are modeled with mass and thus they are subject to gravitational and inertial
      forces. As result, we obtain smooth, filtered and compact trajectory bundles.
      This gravitational interaction can be seen as a flocking behavior among particles
      that promotes better and robust axon fiber estimations because they use
      collective information to move. However, the stochastic walks may generate paths
      with low support (outliers), generally associated to incorrect brain connections.
      In order to eliminate the outlier pathways, we propose a filtering procedure
      based on principal component analysis and spectral clustering. The performance of
      the proposal is evaluated on Multiple Intra-Voxel Diffusion Orientations from two
      realistic numeric diffusion phantoms and a physical diffusion phantom.
      Additionally, we qualitatively demonstrate the performance on in vivo human brain
      data. 

PMID- 24583806
TI  - Biaxial response of ovine spinal cord dura mater.
AB  - The dura mater performs a major functional role in the stability and mechanical
      response of the spinal cord complex. Computational techniques investigating the
      etiology of spinal cord injury require an accurate mechanical description of the
      dura mater. Previous studies investigating the mechanical response of the dura
      mater have reported conflicting results regarding the anisotropic stiffness of
      the dura in the longitudinal and circumferential direction. The aim of this study
      was to investigate the biaxial response of the dura mater in order to establish
      the tissue level mechanical behavior under physiological loading scenarios. To
      this end, square sections of the dura were tested in a custom biaxial setup under
      a comprehensive uniaxial and biaxial loading protocol. The resultant data were
      fit via a transversely isotropic continuum model and an anisotropic continuum
      constitutive model. The transversely isotropic formulation failed to accurately
      predict the dura mater's uniaxial behavior. The anisotropic formulation
      accurately predicted the uniaxial response in both longitudinal and
      circumferential directions. Significantly higher stiffness (p<0.0001) was
      observed in the circumferential direction as compared to the longitudinal
      direction. Further, the longitudinal direction displayed a significantly lower
      degree of nonlinearity (p<0.045) and significantly higher degree of collagen
      fiber dispersion (p<0.032) as compared to the circumferential direction. Results
      indicate that the dura mater has differential mechanical response in the
      longitudinal and circumferential directions and future studies should utilize an
      anisotropic two fiber family continuum model to accurately describe dura mater
      mechanics. 

PMID- 24583807
TI  - Possible role of ZPAC, zygote-specific proteasome assembly chaperone, during
      spermatogenesis in the mouse.
AB  - In the mammalian testis, the ubiquitin-proteasome system plays important roles in
      the process that promotes the formation of mature sperm. We recently identified
      zygote-specific proteasome assembly chaperone (ZPAC), which is specifically
      expressed in the mouse gonads and zygote. ZPAC mediates a unique proteasome
      assembly pathway in the zygote, but the expression profile and function of ZPAC
      in the testis is not fully understood. In this study, we investigated the
      possible role of ZPAC during mouse spermatogenesis. First, we analyzed the
      expression of ZPAC and 20S proteasome subunit alpha4/PSMA7 in the adult mouse
      testis. ZPAC and alpha4 were expressed in spermatogonia, spermatocytes, and round
      spermatids. In elongating spermatids, ZPAC was expressed until step 10, whereas
      expression of alpha4 persisted until step 12. We then examined the expression
      profile of ZPAC and alpha4 in a mouse model of experimental unilateral
      cryptorchidism. Consistent with appearance of morphologically impaired germ cells
      following cryptorchidism, the ZPAC protein level was significantly decreased at 4
      days post induction of experimental cryptorchidism (D4) compared with the intact
      testis, although the amount of alpha4 protein persisted at least until D10.
      Moreover, intense ZPAC staining was co-localized with staining of annexin V, an
      early indicator of apoptosis in mammalian cells, in germ cells of cryptorchid
      testis, but ZPAC was also expressed in germ cells showing no detectable
      expression of annexin V. These results suggest that ZPAC plays a role during
      spermatogenesis and raises the possibility that 20S proteasome mediated by ZPAC
      may be involved in the regulation of germ cell survival during spermatogenesis. 

PMID- 24583809
TI  - Influence of shear force on floc properties and residual aluminum in humic acid
      treatment by nano-Al13.
AB  - The impacts of various shear forces on floc sizes and structures in humic acid
      coagulations by polyaluminum chloride (PACl) and nano-Al13 were comparatively
      studied in this paper. The dynamic floc size was monitored by use of a laser
      diffraction particle sizing device. The floc structure was evaluated in terms of
      fractal dimension, analyzed by small-angle laser light scattering (SALLS). The
      effect of increased shear rate on residual Al of the coagulation effluents was
      then analyzed on the basis of different floc characteristics generated under
      various shear conditions. The results showed that floc size decreased with the
      increasing shear rate for both Al13 and PACl. Besides, floc strength and re
      formation ability were also weakened by the enhanced shear force. Al13 resulted
      in small, strong and better recoverable flocs than PACl and moreover, in the
      shear range of 100-300 revolution per minute (rpm) (G=40.7-178.3s(-1)), the
      characteristics of HA-Al13 flocs displayed smaller scale changes than those of HA
      PACl flocs. The results of residual Al measurements proved that with shear
      increased, the residual Al increased continuously but Al13 presented less
      sensitivity to the varying shear forces. PACl contributed higher residual Al than
      Al13 under the same shear condition.

PMID- 24583808
TI  - Microdroplet in vitro fertilization can reduce the number of spermatozoa
      necessary for fertilizing oocytes.
AB  - Successful in vitro fertilization (IVF) in mice has been achieved using
      spermatozoa at concentrations specifically optimized for the experimental
      conditions, such as species and source of spermatozoa. Although IVF in mice is
      mostly performed using about 80-500 ul drops, it is expected that the number of
      spermatozoa used for insemination can be reduced by decreasing the size of the
      IVF drops. The present study was undertaken to examine the extent to which the
      number of spermatozoa used for IVF could be reduced by using small droplets (1
      ul). We devised the experimental parameters using frozen-thawed spermatozoa from
      C57BL/6 mice in anticipation of broader applications to other mouse facilities.
      We found that as few as 5 spermatozoa per droplet could fertilize oocytes (1 or 3
      oocytes per droplet), although the fertilization rates were low (13-15%).
      Practical fertilization rates (> 40%) could be achieved with frozen-thawed
      C57BL/6J spermatozoa, which are sensitive to cryopreservation, when 20 sperm per
      droplet were used to inseminate 3 oocytes. Even with spermatozoa from a very poor
      quality suspension (10% motility), about 25% of oocytes were fertilized. Our
      calculations indicate that the number of inseminated spermatozoa per oocyte can
      be reduced to 1/96-1/240 by this method. In two separate embryo transfer
      experiments, 60% and 47%, respectively, of embryos developed to term. Our
      microdroplet IVF method may be particularly advantageous when only a limited
      number of motile spermatozoa are available because of inadequate freezing-thawing
      or genetic reasons. 

PMID- 24583810
TI  - Ferric ion mediated photodecomposition of aqueous perfluorooctane sulfonate
      (PFOS) under UV irradiation and its mechanism.
AB  - Perfluorooctane sulfonate (PFOS) recently has received much attention due to its
      global distribution, environmental persistence and bioaccumulation. The methods
      for PFOS decomposition are very limited due to its inertness. In this report we
      first found the photodecomposition of PFOS under UV was greatly accelerated by
      addition of ferric ions. In the presence of ferric ion (100 MUM), PFOS (20 MUM)
      decreased to below the detection limit within 48 h, with the rate constant of
      1.67 d(-1), which was 50 times higher than that by direct photolysis (0.033 d(
      1)). Besides fluoride and sulfate ions, C2-C8 perfluorocarboxylic acids (PFCAs)
      were identified as the main intermediates. It was found that addition of PFOS
      into the FeCl3 aqueous solution led to reduction of UV absorption, and the
      presence of ferric ion reduced the response of PFOS as analyzed by UPLC-MS/MS,
      which indicated that PFOS formed a complex with ferric ion. The ESR detection
      indicated that the electronic state of Fe(3+)-PFOS complex changed during
      reaction. And the role of oxygen and hydroxyl radical on the defluorination of
      PFOS was investigated. Accordingly the mechanism for PFOS photodecomposition in
      the presence of ferric ion was proposed.

PMID- 24583811
TI  - Kyphosus gladius, a new species of sea chub from Western Australia (Teleostei:
      Kyphosidae), with comments on Segutilum klunzingeri Whitley.
AB  - Two morphologically distinct forms of the nominal species Kyphosus sydneyanus
      (Gunther, 1886) (Kyphosidae) were discerned while collecting off Western
      Australia near Perth in 2009. A morphological comparison with recognized species
      of Kyphosus and an analysis of mtDNA (Cytochrome b, control region, 12S and 16S)
      and three nDNA markers (RAG1, RAG2 and Tmo-4C4) demonstrated that the more
      elongate of these forms was an undescribed species of Kyphosus. It differs from
      congeners in the Pacific and Indian Oceans in the combination of the following
      characters: green bar on the operculum, 11-12 dorsal soft fin rays, depth of
      caudal peduncle 9.9-11.8 % SL, body depth 33.3-41.6 % SL, 55-63 scales in lateral
      line, 12-16 interorbital scales, 44-55 pored scales in the lateral line, 3-5 gill
      rakers on upper limb of first gill arch internally, 11-15 gill rakers on lower
      limb of first gill arch internally, 15-19 total gill rakers on first gill arch,
      and by having 10 precaudal vertebrae and 16 caudal vertebrae. Examination of
      museum specimens and available underwater photographs suggests that the new
      species is restricted to Western Australia, and to date it has been recorded
      between the Houtman Abrolhos Islands and Albany. Discrepancies between the type
      specimen and original description of Segutilum klunzingeri Whitley made it
      impossible to determine the relationship between this taxon and the new species
      from Western Australia, and thus we consider S. klunzingeri a nomen dubium. 

PMID- 24583812
TI  - The true identity of Neoneura bilinearis Selys, 1860, with the synonymy of N.
      gaida Racenis, 1953, and the description of N. confundens sp. nov. (Odonata:
      Protoneuridae).
AB  - Study of rough notes and sketches made by D.C. Geijskes in 1972 and the recently
      found original drawings by E. de Selys Longchamps done in 1884 from the male
      syntype of Neoneura bilinearis Selys, 1860, shows the syntype male and female
      (now lost for several decades) of N. bilinearis refer to the same species later
      described as Neoneura gaida Racenis, 1953. Therefore N. gaida is considered a
      junior synonym of N. bilinearis Selys, 1860. A neotype is chosen for the true N.
      bilinearis (neotype ?, Suriname, Kabalebo, 15 viii 1965, in RMNH). N. bilinearis
      sensu Williamson (1917) is redescribed as Neoneura confundens sp. nov. (holotype
      ?, Suriname, Jodensavanna, Koela-kreek, 13 ii 1946, in RMNH). N. confundens has a
      wide distribution in South America north of the Tropic of Capricorn, but it is
      lacking from the central and lower Amazon. It occurs in several color morphs and
      also varies in male appendage, genital ligula, and female pronotum morphology. 

PMID- 24583813
TI  - Revision of the genus Eusyllis Malmgren, 1867 (Annelida: Phyllodocida: Syllidae:
      Eusyllinae), with the description of a new species from the eastern Pacific
      Ocean.
AB  - Eusyllis Malmgren, 1867 (Annelida, Syllidae) is revised, with 7 species
      considered as valid (Eusyllis assimilis Marenzeller, 1875; Eusyllis blomstrandi
      Malmgren, 1867; Eusyllis kupfferi Langerhans, 1879; Eusyllis lamelligera Marion &
      Bobretzky, 1875; Eusyllis longicirrata Imajima, 1966; Eusyllis maxima (Monro,
      1930); and Eusyllis nuchalata Hartmann-Schroder, 1965) plus a newly described
      species (Eusyllis grandmarie n. sp.) the only species of the genus recorded from
      a whale carcass, lying at more than 600 m deep in the eastern Pacific Ocean off
      the California coast. The new species is characterized by elongated compound
      chaetae, with blades almost unidentate, and a thin, spine-like proximal tooth. It
      differs from Eusyllis longicirrata Imajima, 1966, from Japan, in having shorter
      dorsal cirri and blades of compound chaetae. Additionally, Eusyllis nuchalata
      Hartmann-Schroder, 1965 is re-described. A key to the species of the genus is
      included. 

PMID- 24583814
TI  - A new species of the genus Rhopalaea (Class: Ascidiacea) from the Red Sea.
AB  - During regular surveys and collection of ascidians along the Red Sea coast of
      Israel, several specimens of an undescribed species of Rhopalaea were collected.
      Samples were collected by SCUBA from the natural coral reef and man-made
      structures at depths between 10 to 40m. This is the first species of the genus
      Rhopalaea described from the Red Sea, which is characterized by a transparent,
      uncolored gelatinous tunic with elongated attachment extensions, and is
      distinguished by its eight atrial lobes, thoracic muscle arrangement, and
      branchial sac structure. 

PMID- 24583815
TI  - New taxa of Tanyderidae (Diptera) from Eocene Baltic amber.
AB  - Macrochile hornei sp. nov. from Baltic amber (Upper Eocene) is described and
      illustrated. Podemacrochile gen. nov. is described with Podemacrochile baltica
      (Podenas, 1997) as type species. A key to the genera and species of Tanyderidae
      known from Baltic amber is presented. 

PMID- 24583816
TI  - Pacificulla gen. nov. of Lecithoceridae (Lepidoptera, Gelechioidea) from New
      Guinea, with descriptions of six new species.
AB  - Pacificulla Park, gen. nov. related to Crocanthes Meyrick is described from New
      Guinea, based on the type species P. flaviagra Park, sp. nov. Five additional
      species are described: P. esdiparki Park, sp. nov., P. searsi Park, sp. nov., P.
      callisomata Park, sp. nov., P. cervicalis Park, sp. nov., and P. kekamatana Park,
      sp. nov. The following six new combinations are proposed, the species of which
      were formerly included in Crocanthes: Pacificulla thrasydora (Meyrick, 1910),
      comb. nov.; P. philotima (Diakonoff, 1954), comb. nov.; P. miltina (Durrant,
      1915), comb. nov.; P. ignigera (Meyrick, 1938), comb. nov.; P. zonias (Meyrick,
      1904), comb. nov.; and P. geniola (Meyrick, 1931), comb. nov. C. xanthorrhoea
      Diakonoff is synonymized with P. philotima (Diakonoff). The upper surface of
      adults, labial palpi, and genitalia of all described species are illustrated,
      including the wing venation of two representative species. 

PMID- 24583817
TI  - Checklist of the ancyrocephalids (Monogenea) parasitizing Tilapia species in
      Cameroon, with the description of three new species.
AB  - A checklist of the 23 species of Ancyrocephalidae (Monogenea) parasitizing
      Tilapia species sampled from both sides of the Cameroon Volcanic Line is
      provided. As already reported elsewhere, Cichlidogyrus aegypticus in Cameroon
      shows two different shape of its vagina, and C. tilapiae, C. arthracanthus and C.
      tiberianus were found on a wide range of host species. Among the 23 studied
      species of Monogenea, three are considered new species and are described herein:
      Cichlidogyrus berminensis n. sp. from Tilapia bemini, characterized by a short
      penis with marked narrow heel, a simple and straight accessory piece ending in a
      large hook, and a medium sized pair of uncinuli I; Cichlidogyrus gillesi n. sp.
      from Tilapia guineensis, characterized by a large and trapezoid heel of the penis
      and a S-shaped and wrinkle walled vagina; and Scutogyrus vanhovei n. sp. from
      Tilapia mariae, characterized by the presence of a distinct swollen portion of
      the penis. From a parasite's point of view, the CVL has no influence on species
      dispersion/distribution. 

PMID- 24583818
TI  - Bambuina bambui: a new genus and species of cave cricket from Brazil (Orthoptera:
      Grylloidea: Phalangopsidae: Luzarinae).
AB  - Bambuina bambui, um novo genero e especie de grilo falangopsideo e descrito a
      partir de especimes obtidos na Gruta do Centenario, uma caverna de quartzo
      localizada na Serra do Inficionado, um subconjunto de montanhas pertencentes ao
      complexo da Serra do Caraca no estado de Minas Gerais, Brasil. 

PMID- 24583819
TI  - A new species of Urodeta (Lepidoptera: Elachistidae: Elachistinae) from Nepal,
      the first record of the genus from Asia, showing an ancient distribution pattern.
AB  - A new species, Urodeta noreikai Sruoga & De Prins, is described from the Nepalese
      Himalayas. The habitus and genitalia of both sexes are diagnosed and illustrated
      in detail. This discovery constitutes the first record of the occurrence of the
      genus Urodeta Stainton, 1869 in Asia and its biogeographic significance is
      discussed. 

PMID- 24583820
TI  - Association between preoperative glucocorticoids and long-term survival and
      cancer recurrence after colectomy: follow-up analysis of a previous randomized
      controlled trial.
AB  - BACKGROUND: The effect of anaesthetic drugs on long-term oncological outcomes
      after cancer surgery is an area of current interest. Dexamethasone is widely used
      in anaesthetic practice; however, its effect on long-term survival and cancer
      outcomes is not known. This study presents the results of a 5-yr follow-up of
      patients receiving dexamethasone before elective colectomy as part of a previous
      randomized clinical trial. METHODS: Sixty patients who underwent elective open
      colonic resection for any indication between June 2006 and March 2008 were
      randomized to receive either 8 mg i.v. dexamethasone or placebo before surgery. A
      5-yr follow-up analysis was conducted to evaluate overall survival, disease-free
      survival and recurrence specifically for patients undergoing resection for Stage
      I-III colon cancer. Kaplan-Meier analysis was performed and log-rank test was
      used to evaluate difference in survival between groups. RESULTS: Forty-three of
      the 60 subjects had Stage I-III colon cancer and were included in the follow-up
      analysis. Twenty received preoperative dexamethasone and 23 received placebo.
      There were no significant differences between groups in baseline or disease
      characteristics. No differences were found between groups for overall or disease
      free survival. In the dexamethasone group, there was a significantly higher rate
      of distant recurrence (6 compared with 1, P=0.04). CONCLUSIONS: Preoperative
      dexamethasone was associated with a higher rate of distant recurrence in patients
      undergoing colectomy for colon cancer. Given the small sample size, this finding
      should be interpreted with caution, but warrants further investigation in a
      prospective study.

PMID- 24583821
TI  - III. Fibrinogen concentrate: clinical reality and cautious Cochrane
      recommendation.

PMID- 24583822
TI  - Immune regulation by low doses of the DNA methyltransferase inhibitor 5
      azacitidine in common human epithelial cancers.
AB  - Epigenetic therapy is emerging as a potential therapy for solid tumors. To
      investigate its mechanism of action, we performed integrative expression and
      methylation analysis of 63 cancer cell lines (breast, colorectal, and ovarian)
      after treatment with the DNA methyltransferase inhibitor 5-azacitidine (AZA).
      Gene Set Enrichment Analysis demonstrated significant enrichment for
      immunomodulatory pathways in all three cancers (14.4-31.3%) including interferon
      signaling, antigen processing and presentation, and cytokines/chemokines. Strong
      upregulation of cancer testis antigens was also observed. An AZA IMmune gene set
      (AIMs) derived from the union of these immunomodulatory pathway genes classified
      primary tumors from all three types, into "high" and "low" AIM gene expression
      subsets in tumor expression data from both TCGA and GEO. Samples from selected
      patient biopsies showed upregulation of AIM genes after treatment with epigenetic
      therapy. These results point to a broad immune stimulatory role for DNA
      demethylating drugs in multiple cancers. 

PMID- 24583823
TI  - Hidden blue hazard? LED lighting and retinal damage in rats.

PMID- 24583825
TI  - Letter to the editor: "cyclosporin A in left ventricular remodeling after
      myocardial infarction".

PMID- 24583824
TI  - Evaluating a brief, internet-based intervention for co-occurring depression and
      problematic alcohol use in young people: protocol for a randomized controlled
      trial.
AB  - BACKGROUND: Depression and alcohol misuse represent two of the major causes of
      disease burden in young adults. These conditions frequently co-occur and this co
      occurrence is associated with increased risks and poorer outcomes than either
      disorder in isolation. Integrated treatments have been shown to be effective,
      however, there remains a significant gap between those in need of treatment and
      those receiving it, particularly in young people. The increased availability of
      Internet-based programs to complement health care presents a unique opportunity
      in the treatment of these conditions. OBJECTIVE: The objective of our study was
      to evaluate whether a brief, Internet-based, self-help intervention (the DEAL
      [DEpression-ALcohol] Project) can be effective in treating co-occurring
      depression and problematic alcohol use in young people (18-25 years old).
      METHODS: The evaluation will take the form of a randomized controlled trial
      (RCT), comparing the DEAL Project with an attention-control condition
      (HealthWatch). The RCT will consist of a four-week intervention phase and a 24
      week follow-up. It will be entirely Internet-based and open Australia-wide to
      young people 18 to 25 years old. The primary outcomes will be change in
      depression symptoms and alcohol use at 5, 12, and 24 weeks post baseline.
      Secondary outcomes include change in general functioning and quality of life,
      anxiety/stress symptomatology, and a number of other depression/alcohol related
      outcomes. Process analysis will also measure engagement across the conditions.
      RESULTS: This study is currently ongoing with preliminary results expected in
      late 2014. CONCLUSIONS: This study, to our knowledge, will be the first RCT of a
      Internet-based treatment for comorbid depression and problematic alcohol use in
      any age group. If successful, the program represents a novel and innovative
      approach to addressing the significant harms associated with these conditions and
      will be an invaluable resource to those not receiving help elsewhere. TRIAL
      REGISTRATION: Australian New Zealand Clinical Trials Registry;
      ACTRN12613000033741;
      https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=363461 (Archived
      by WebCite at http://www.webcitation.org/6Mrg9VFX4).

PMID- 24583827
TI  - Sensitive detection of surface- and size-dependent direct and indirect band gap
      transitions in ferritin.
AB  - Ferritin is a protein nano-cage that encapsulates minerals inside an 8 nm cavity.
      Previous band gap measurements on the native mineral, ferrihydrite, have reported
      gaps as low as 1.0 eV and as high as 2.5-3.5 eV. To resolve this discrepancy we
      have used optical absorption spectroscopy, a well-established technique for
      measuring both direct and indirect band gaps. Our studies included controls on
      the protein nano-cage, ferritin with the native ferrihydrite mineral, and
      ferritin with reconstituted ferrihydrite cores of different sizes. We report
      measurements of an indirect band gap for native ferritin of 2.140 +/- 0.015 eV
      (579.7 nm), with a direct transition appearing at 3.053 +/- 0.005 eV (406.1 nm).
      We also see evidence of a defect-related state having a binding energy of 0.220
      +/- 0.010 eV . Reconstituted ferrihydrite minerals of different sizes were also
      studied and showed band gap energies which increased with decreasing size due to
      quantum confinement effects. Molecules that interact with the surface of the
      mineral core also demonstrated a small influence following trends in ligand field
      theory, altering the native mineral's band gap up to 0.035 eV.

PMID- 24583826
TI  - Reply to "letter to the editor: 'cyclosporin A in left ventricular remodeling
      after myocardial infarction'".

PMID- 24583828
TI  - Plant-microbe interactions as drivers of ecosystem functions relevant for the
      biodegradation of organic contaminants.
AB  - The plant organism and associated microbial communities can be seen as a sunlight
      driven hotspot for the turnover of organic chemicals. In such environments the
      fate of a chemical will not only depend on its intrinsic structural stability
      toward (bio-)chemical reactions and its bioavailability but also on the
      functional effectiveness and stability of natural microbial communities as main
      drivers of natural attenuation of chemicals. Recent research demonstrates that
      interactions between plants and microorganisms are crucial for the
      biotransformation of organic chemicals, for various processes affecting the
      bioavailability of such compounds, and for the stability of the affected
      ecosystem. Practical bioremediation approaches, therefore, should encompass
      integrated measures targeting functional vegetation as well as functional
      microbial communities. Good examples for a successful practical approach are
      constructed wetlands, where an artificial, simplified ecosystem is used for the
      detoxification of organic contaminants. While such systems have considerable
      practical success, they are often treated as a black box and a sound mechanistic
      understanding of functional resilience and of the 'reactive power' of such plant
      microbe ecosystems is poor. This situation has to change, if progress in the
      application of bioremediation is to be made. 

PMID- 24583829
TI  - Yes, the government should tax soft drinks: findings from a citizens' jury in
      Australia.
AB  - Taxation has been suggested as a possible preventive strategy to address the
      serious public health concern of childhood obesity. Understanding the public's
      viewpoint on the potential role of taxation is vital to inform policy decisions
      if they are to be acceptable to the wider community. A Citizens' Jury is a
      deliberative method for engaging the public in decision making and can assist in
      setting policy agendas. A Citizens' Jury was conducted in Brisbane, Australia in
      May 2013 to answer the question: Is taxation on food and drinks an acceptable
      strategy to the public in order to reduce rates of childhood obesity? Citizens
      were randomly selected from the electoral roll and invited to participate.
      Thirteen members were purposively sampled from those expressing interest to
      broadly reflect the diversity of the Australian public. Over two days,
      participants were presented with evidence on the topic by experts, were able to
      question witnesses and deliberate on the evidence. The jurors unanimously
      supported taxation on sugar-sweetened drinks but generally did not support
      taxation on processed meats, snack foods and foods eaten/ purchased outside the
      home. They also supported taxation on snack foods on the condition that traffic
      light labelling was also introduced. Though they were not specifically asked to
      deliberate strategies outside of taxation, the jurors strongly recommended more
      nutritional information on all food packaging using the traffic light and
      teaspoon labelling systems for sugar, salt and fat content. The Citizens' Jury
      suggests that the general public may support taxation on sugar-sweetened drinks
      to reduce rates of obesity in children. Regulatory reforms of taxation on sugar
      sweetened drinks and improved labelling of nutritional information on product
      packaging were strongly supported by all members of the jury. These reforms
      should be considered by governments to prevent childhood obesity and the future
      burden on society from the consequences of obesity. 

PMID- 24583830
TI  - Effects of moderate strength cold air exposure on blood pressure and biochemical
      indicators among cardiovascular and cerebrovascular patients.
AB  - The effects of cold air on cardiovascular and cerebrovascular diseases were
      investigated in an experimental study examining blood pressure and biochemical
      indicators. Zhangye, a city in Gansu Province, China, was selected as the
      experimental site. Health screening and blood tests were conducted, and finally,
      30 cardiovascular disease patients and 40 healthy subjects were recruited. The
      experiment was performed during a cold event during 27-28 April 2013. Blood
      pressure, catecholamine, angiotensin II (ANG-II), cardiac troponin I (cTnI),
      muscle myoglobin (Mb) and endothefin-1 (ET-1) levels of the subjects were
      evaluated 1 day before, during the 2nd day of the cold exposure and 1 day after
      the cold air exposure. Our results suggest that cold air exposure increases blood
      pressure in cardiovascular disease patients and healthy subjects via the
      sympathetic nervous system (SNS) that is activated first and which augments ANG
      II levels accelerating the release of the norepinephrine and stimulates the renin
      angiotensin system (RAS). The combined effect of these factors leads to a rise in
      blood pressure. In addition, cold air exposure can cause significant metabolism
      and secretion of Mb, cTnI and ET-1 in subjects; taking the patient group as an
      example, ET-1 was 202.7 ng/L during the cold air exposure, increased 58 ng/L
      compared with before the cold air exposure, Mb and cTnI levels remained
      relatively high (2,219.5 ng/L and 613.2 ng/L, increased 642.1 ng/L and 306.5 ng/L
      compared with before the cold air exposure, respectively) 1-day after the cold
      exposure. This showed that cold air can cause damage to patients' heart cells,
      and the damage cannot be rapidly repaired. Some of the responses related to the
      biochemical markers indicated that cold exposure increased cardiovascular strain
      and possible myocardial injury.

PMID- 24583831
TI  - Impact of stinging jellyfish proliferations along south Italian coasts: human
      health hazards, treatment and social costs.
AB  - Stinging jellyfish outbreaks represent a health hazard, causing contact
      dermatitis and systemic reactions. This study investigated the epidemiology,
      severity, and treatment protocols of jellyfish stings in a coastal area with high
      tourist development and frequent stinging jellyfish outbreaks of the central
      Mediterranean (Salento, Southern Italy), and the associated costs for the Italian
      National Health Service. In 2007-2011, 1,733 bathers (mostly children and
      females) sought medical assistance following jellyfish stings, the main cause of
      human pathologies due to contact with marine organisms. The majority of events
      were reported in the years 2007-2009, whereas the occurrence of cnidarian
      jellyfish outbreaks has been increasingly reported in the same area since summer
      2010. Most symptoms were limited to local and cutaneous reactions; conversely,
      8.7% of cases evoked complications, mainly due to allergic reactions. The main
      drugs used were corticosteroids, locally applied and systemic (46% and 43%,
      respectively), and with ammonia (74%) as the main non-pharmacological treatment.
      The estimated cost of jellyfish-related first-aid services along the Salento
      coastline over the 5-year period was approximately 400,000 Euros. Therefore the
      management of jellyfish outbreak phenomena need coordinated research efforts
      towards a better understanding of underlying ecological mechanisms, together with
      the adoption of effective prevention policy, mitigation strategies, and
      appropriate planning of health services at tourist hot spots. 

PMID- 24583833
TI  - Clues to arsenic's toxicity: microbiome alterations in the mouse gut.

PMID- 24583832
TI  - Flow-induced regulation of brain endothelial cells in vitro.
AB  - Endothelial cell (EC) function and susceptibility to vascular disease are
      regulated by flow; this relationship has been modeled in systemic, but not
      cerebrovascular, EC culture. We studied the effects of unidirectional flow of
      medium, produced by orbital rotation of cultures, on morphology and protein
      expression in bEnd.3 mouse brain ECs. Flow altered the expression of key
      transcription factors and gasotransmitter-synthesizing enzymes, and increased NO
      production. Statins and angiotensin receptor blockers reproduced the effect of
      flow on endothelial nitric oxide synthase expression. Thus, flow modified brain
      EC properties and function in vitro, with similarities and possible differences
      compared to previous studies on systemic ECs. Thus, the effect of flow on brain
      ECs can be modeled in vitro and may assist the investigation of mechanisms of
      cerebrovascular disease. 

PMID- 24583834
TI  - Wagner-Meissner-like corpuscles in gastric mucosa: a brief report.
AB  - Wagner-Meissner corpuscles are touch receptors that are located in dermal
      papillae and are usually absent in gastrointestinal mucosa. Wagner-Meissner-like
      corpuscles have been reported in association with benign neural neoplasm. A case
      of Wagner-Meissner-like corpuscles in endoscopically normal gastric mucosa biopsy
      of a 48-year-old woman is presented here. The corpuscles were positive for S-100
      and clinical evidence of neurofibromatosis was negative. From a review of the
      literature, only 2 cases of tactile corpuscle-like structures in gastric mucosa
      are available. 

PMID- 24583835
TI  - Invasive Paget disease of the nipple: a brief review of the literature and report
      of the first case with axillary nodal metastases.
AB  - Although Paget disease of the nipple (PDN) is a well-established clinical and
      pathological neoplastic process, invasive PDN (IPDN) is a relatively newly
      described disease. The latter entity is characterized by invasive carcinoma that
      is localized to the nipple and is associated with PDN as well as with either
      intraductal and/or invasive carcinoma in the underlying breast. To our knowledge,
      only 17 cases of IPDN, all node negative, have been reported. Here, we report the
      case of a 68-year-old woman with invasive Paget disease of the left nipple. The
      patient had a history of intraductal carcinoma, treated by lumpectomy alone. She
      presented 6 years later with "eczematous" lesion of the ipsilateral nipple, a
      punch biopsy of which showed a superficially IPDN as well as conventional PDN.
      The subsequently performed wide excision of the nipple, areola, and underlying
      breast tissue showed the invasive carcinoma to span 0.6 cm. Then, 3 months later,
      the patient presented with ipsilateral palpable axillary lymphadenopathy.
      Axillary dissection revealed metastatic carcinoma in 7 of 19 lymph nodes. This
      case of IPDN not only represents the deepest extent of invasion reported thus far
      but also the only one known to be node positive. 

PMID- 24583836
TI  - Adult biphasic renal tumors.

PMID- 24583837
TI  - ALK-positive inflammatory myofibroblastic tumor of the abdomen with widespread
      microscopic multifocality.
AB  - Inflammatory myofibroblastic tumor (IMT) is a locally aggressive neoplasm, most
      frequently occurring in the abdominal cavity as multiple recurrent nodules. We
      report a case of IMT in a 24-year-old male presenting as multiple nodules
      involving the omentum, the liver, and the colon. Spindle tumor cells expressed
      ALK with a cytoplasmic granular distribution, the CLTC-ALK fusion gene was
      demonstrated by reverse-transcriptase polymerase chain reaction analysis, and
      break-apart fluorescence in situ hybridization (FISH) probes for the ALK gene
      showed a pathological pattern (single red signal associated with 1/2 normal fused
      signals) highly suggestive for combined gene fusion and deletion. To reduce the
      surgically unresectable liver mass, the patient was treated with crizotinib, and
      after 4 months of treatment the disease was defined stable according to RECIST
      criteria. Interestingly, ALK and FISH/FICTION analysis revealed that tumor cells
      were widely dispersed as multiple microscopic foci or as single cells beneath the
      omental mesothelium. These findings indicate that IMT multifocality might result
      either from dissemination from the main tumor mass or development of multiple
      independent neoplastic foci; furthermore, they underline the need of omentectomy
      in abdominal IMT to obtain surgical radicality. 

PMID- 24583838
TI  - Hyaline globules in mammary myofibroblastoma: a case report.
AB  - A 52-year-old otherwise healthy woman presented with a solitary firm mass in the
      right breast. Histopathological evaluation of the 1.5-cm mass showed a mammary
      myofibroblastoma of the conventional spindle-cell type. High-power examination of
      hematoxylin-eosin-stained sections showed round, eosinophilic, intracytoplasmic,
      as well as extracellular, hyaline globules. These 5- to 20-um globules appeared
      gray with a pinkish rim on Masson's trichrome stain. Immunohistochemically, the
      hyaline globules were strongly reactive with smooth muscle myosin heavy chain,
      desmin, and caldesmon. Histologically similar inclusion bodies have been reported
      in phylloides tumors--including those with myoid differentiation. To our
      knowledge, this is the first description of hyaline globules, a peculiar
      histological curiosity with no known clinical significance, in mammary
      myofibroblastoma.

PMID- 24583839
TI  - Impact of hydraulic retention time on organic and nutrient removal in a membrane
      coupled sequencing batch reactor.
AB  - Although solids retention time (SRT) is the key parameter in wastewater treatment
      design and operation, this study determined the effect of hydraulic retention
      time (HRT) on biological nutrient removal in a membrane coupled sequencing batch
      reactor (MSBR) at the fixed SRT of 10 days. During more than 200 days of
      operation, the HRT of the MSBR were decreased from 24 to 12 and to 6 h while the
      volumetric exchange ratio in each operating cycle was fixed at 50%. The decrease
      of HRT led to a proportional increase in biomass concentration at the fixed SRT.
      The system demonstrated excellent removal of organic matter with the highest COD
      removal efficiency (97%) achieved at the shortest HRT of 6 h. As HRT was reduced
      from 24 to 12 h, the total nitrogen removal efficiency improved from 68 +/- 5% to
      80 +/- 4%, but there was no further improvement when HRT decreased to 6 h.
      Coincidently, similar and higher abundance of nitrifying bacteria was observed in
      the MSBR operated at the HRTs of 6 and 12 h than that at the HRT of 24 h. The
      total phosphorus removal efficiencies were 62 +/- 15%, 77 +/- 4% and 85 +/- 3% at
      the HRTs of 24, 12 and 6 h, respectively. The maximum P release rates for
      activated sludge at the HRTs of 24, 12 and 6 h were 3.7 +/- 0.5, 6.4 +/- 0.2 and
      8.7 +/- 0.1 mg P/h, respectively, while the maximum P uptake rates were 3.2 +/-
      0.1, 8.6 +/- 0.2 and 15.2 +/- 0.2 mg P/h, respectively. Contradictory to the
      theory that effluent water quality is solely SRT dependent, the results suggest
      that it is also affected by HRT and resultant biomass concentration possibly due
      to factors such as change in hydrolysis of particulate organic matter, the unique
      microenvironment and transition between anaerobic and aerobic metabolism at high
      biomass concentrations in MSBR operation. 

PMID- 24583840
TI  - Investigation of Cr(VI) reduction and Cr(III) immobilization mechanism by
      planktonic cells and biofilms of Bacillus subtilis ATCC-6633.
AB  - In this study, we investigated the Cr(VI) uptake mechanism of planktonic cells
      and biofilms of Bacillus subtilis (B. subtilis) ATCC-6633. Data showed that the
      effect of planktonic cells on the Cr(VI) uptake was quite different from that of
      biofilms. Planktonic cells had strong ability of Cr(VI) reduction, while biofilms
      possessed a great potential of Cr(III) immobilization. For planktonic cells, 100
      mg/L Cr(VI) could be completely reduced. Both exopolymeric substances and
      cytoplasmic extracts contributed to high capacity of Cr(VI) reduction. After the
      reduction, noticeable Cr(III) precipitates were accumulated on bacterial
      surfaces, but 37.5% Cr(III) still remained in the supernatant. For biofilms, the
      biofilm debris became the main active ingredient of the Cr(VI) reduction.
      However, only 20 mg/L Cr(VI) could be reduced probably because of unavailability
      of reducing active sites during the biofilm formation. Further studies showed
      that biofilms had a better Cr(III) immobilization capacity than planktonic cells
      with 100% Cr(III) immobilized. Moreover, for the first time, we proposed a
      strategy combining the advantages of both planktonic cells and biofilms, and a
      successful Cr(VI) removal from typical Cr(VI)-containing plating wastewater was
      achieved through a 10-L pilot-scale experiment. 

PMID- 24583841
TI  - Role of competing ions in the mobilization of arsenic in groundwater of Bengal
      Basin: insight from surface complexation modeling.
AB  - This study assesses the role of competing ions in the mobilization of arsenic
      (As) by surface complexation modeling of the temporal variability of As in
      groundwater. The potential use of two different surface complexation models
      (SCMs), developed for ferrihydrite and goethite, has been explored to account for
      the temporal variation of As(III) and As(V) concentration, monitored in shallow
      groundwater of Bengal Basin over a period of 20 months. The SCM for ferrihydrite
      appears as the better predictor of the observed variation in both As(III) and
      As(V) concentrations in the study sites. It is estimated that among the competing
      ions, PO4(3-) is the major competitor of As(III) and As(V) adsorption onto Fe
      oxyhydroxide, and the competition ability decreases in the order PO4(3-) ? Fe(II)
      > H4SiO4 = HCO3(-). It is further revealed that a small change in pH can also
      have a significant effect on the mobility of As(III) and As(V) in the aquifers. A
      decrease in pH increases the concentration of As(III), whereas it decreases the
      As(V) concentration and vice versa. The present study suggests that the reductive
      dissolution of Fe oxyhydroxide alone cannot explain the observed high As
      concentration in groundwater of the Bengal Basin. This study supports the view
      that the reductive dissolution of Fe oxyhydroxide followed by competitive
      sorption reactions with the aquifer sediment is the processes responsible for As
      enrichment in groundwater. 

PMID- 24583844
TI  - miR-34a/SIRT6 in squamous differentiation and cancer.

PMID- 24583845
TI  - Phase, microstructure and hydrogen storage properties of Mg-Ni materials
      synthesized from metal nanoparticles.
AB  - After Mg and Ni nanoparticles were fabricated by hydrogen plasma metal reaction,
      Mg-rich MgxNi100-x(75 < x < 90) materials were synthesized from these metal
      nanoparticles to study the synergistic effects for hydrogen storage in these
      samples to show both good kinetics and high capacity. These MgxNi100-x materials
      may absorb hydrogen with a capacity of around 3.3-5.1 wt% in 1 min at 573 K. The
      Mg90Ni10 sample shows a hydrogen capacity of 6.1 wt%. The significant kinetic
      enhancement is thought to be due to the unique nanostructure from the special
      synthesis route, the catalytic effect of the Mg2Ni nano phase, and the
      synergistic effects between the Mg2Ni and Mg phases in the materials. An
      interesting phenomenon which has never been reported before was observed during
      pressure composition isotherm (PCT) measurements. One steep step in the
      absorption process and two obviously separated steps in the desorption process
      during PCT measurements of Mg80Ni20 and Mg90Ni10 samples were observed and a
      possible reason from the kinetic performance of the Mg2Ni and Mg phases in
      absorption and desorption processes was explained. These MgxNi100-x materials
      synthesized from Mg and Ni nanoparticles show high capacity and good kinetics,
      which makes these materials very promising candidates for thermal storage or
      energy storage and utilization for renewable power.

PMID- 24583842
TI  - Hypoxia promotes progesterone synthesis during luteinization in bovine granulosa
      cells.
AB  - To determine whether hypoxia has an effect on luteinization, we examined the
      influence of hypoxia on a model of bovine luteinizing and non-luteinizing
      granulosa cell culture. The granulosa cells were obtained from small antral
      follicles (<= 6 mm in diameter). To induce luteinization, the cells were treated
      for 24 h with insulin (2 ug/ml), forskolin (10 uM) or insulin in combination with
      forskolin at 20% O2. After 24 h, progesterone (P4) production was higher in the
      treated cells, which we defined as luteinizing granulosa cells, than in non
      treated cells, which we defined as non-luteinizing granulosa cells. P4 production
      by non-luteinizing granulosa cells was not affected by hypoxia (24 h at 10% and
      5% O2), while P4 production by granulosa cells treated with insulin in
      combination with forskolin was significantly increased under hypoxia (24 h at 10%
      and 5% O2). Because hypoxia affected P4 production by the luteinizing granulosa
      cells but not by the non-luteinizing granulosa cells, hypoxia seems to promote P4
      production during, rather than before, luteinization. In the cells treated with
      insulin in combination with forskolin, mRNA and protein expression of
      steroidogenic acute regulatory protein (StAR) and protein expression of 3beta
      hydroxysteroid dehydrogenase (3beta-HSD) increased under 10% O2, while mRNA and
      protein expressions of key protein and enzymes in P4 biosynthesis did not
      increase under 5% O2. The overall results suggest that hypoxia plays a role in
      progressing and completing the luteinization by enhancing P4 production through
      StAR as well as 3beta-HSD expressions in the early time of establishing the
      corpus luteum. 

PMID- 24583847
TI  - Activation of VCAM-1 and its associated molecule CD44 leads to increased
      malignant potential of breast cancer cells.
AB  - VCAM-1 (CD106), a transmembrane glycoprotein, was first reported to play an
      important role in leukocyte adhesion, leukocyte transendothelial migration and
      cell activation by binding to integrin VLA-1 (alpha4beta1). In the present study,
      we observed that VCAM-1 expression can be induced in many breast cancer
      epithelial cells by cytokine stimulation in vitro and its up-regulation directly
      correlated with advanced clinical breast cancer stage. We found that VCAM-1 over
      expression in the NMuMG breast epithelial cells controls the epithelial and
      mesenchymal transition (EMT) program to increase cell motility rates and promote
      chemoresistance to doxorubicin and cisplatin in vitro. Conversely, in the
      established MDAMB231 metastatic breast cancer cell line, we confirmed that
      knockdown of endogenous VCAM-1 expression reduced cell proliferation and
      inhibited TGFbeta1 or IL-6 mediated cell migration, and increased
      chemosensitivity. Furthermore, we demonstrated that knockdown of endogenous VCAM
      1 expression in MDAMB231 cells reduced tumor formation in a SCID xenograft mouse
      model. Signaling studies showed that VCAM-1 physically associates with CD44 and
      enhances CD44 and ABCG2 expression. Our findings uncover the possible mechanism
      of VCAM-1 activation facilitating breast cancer progression, and suggest that
      targeting VCAM-1 is an attractive strategy for therapeutic intervention. 

PMID- 24583849
TI  - Non-specific inhibition of ischemia- and acidosis-induced intracellular calcium
      elevations and membrane currents by alpha-phenyl-N-tert-butylnitrone, butylated
      hydroxytoluene and trolox.
AB  - Ischemia, and subsequent acidosis, induces neuronal death following brain injury.
      Oxidative stress is believed to be a key component of this neuronal degeneration.
      Acute chemical ischemia (azide in the absence of external glucose) and acidosis
      (external media buffered to pH 6.0) produce increases in intracellular calcium
      concentration ([Ca2+]i) and inward membrane currents in cultured rat cortical
      neurons. Two alpha-tocopherol analogues, trolox and butylated hydroxytoluene
      (BHT), and the spin trapping molecule alpha-Phenyl-N-tert-butylnitrone (PBN) were
      used to determine the role of free radicals in these responses. PBN and BHT
      inhibited the initial transient increases in [Ca2+]i, produced by ischemia,
      acidosis and acidic ischemia and increased steady state levels in response to
      acidosis and the acidic ischemia. BHT and PBN also potentiated the rate at which
      [Ca2+]i increased after the initial transients during acidic ischemia. Trolox
      inhibited peak and sustained increases in [Ca2+]i during ischemia. BHT inhibited
      ischemia induced initial inward currents and trolox inhibited initial inward
      currents activated by acidosis and acidic ischemia. Given the inconsistent
      results obtained using these antioxidants, it is unlikely their effects were due
      to elimination of free radicals. Instead, it appears these compounds have non
      specific effects on the ion channels and exchangers responsible for these
      responses. 

PMID- 24583848
TI  - Interactive association of drugs binding to human serum albumin.
AB  - Human serum albumin (HSA) is an abundant plasma protein, which attracts great
      interest in the pharmaceutical industry since it can bind a remarkable variety of
      drugs impacting their delivery and efficacy and ultimately altering the drug's
      pharmacokinetic and pharmacodynamic properties. Additionally, HSA is widely used
      in clinical settings as a drug delivery system due to its potential for improving
      targeting while decreasing the side effects of drugs. It is thus of great
      importance from the viewpoint of pharmaceutical sciences to clarify the
      structure, function, and properties of HSA-drug complexes. This review will
      succinctly outline the properties of binding site of drugs in IIA subdomain
      within the structure of HSA. We will also give an overview on the binding
      characterization of interactive association of drugs to human serum albumin that
      may potentially lead to significant clinical applications. 

PMID- 24583850
TI  - Transport of glial cell line-derived neurotrophic factor into liposomes across
      the blood-brain barrier: in vitro and in vivo studies.
AB  - Glial cell line-derived neurotrophic factor (GDNF) was encapsulated into
      liposomes in order to protect it from enzyme degradation in vivo and promote its
      permeability across the blood-brain barrier (BBB). In this study, GDNF
      conventional liposomes (GDNF-L) and GDNF target sterically stabilized liposomes
      (GDNF-SSL-T) were prepared. The average size of liposomes was below 90 nm. A
      primary model of BBB was established and evaluated by transendothelial electrical
      resistance (TEER) and permeability. This BBB model was employed to study the
      permeability of GDNF liposomes in vitro. The results indicated that the liposomes
      could enhance transport of GDNF across the BBB and GDNF-SSL-T had achieved the
      best transport efficacy. The distribution of GDNF liposomes was studied in vivo.
      Free GDNF and GDNF-L were eliminated rapidly in the circulation. GDNF-SSL-T has a
      prolonged circulation time in the blood and favorable brain delivery. The values
      of the area under the curve (AUC(0-1 h)) in the brain of GDNF-SSL-T was 8.1 times
      and 6.8 times more than that of free GDNF and GDNF-L, respectively. These results
      showed that GDNF-SSL-T realized the aim of targeted delivery of therapeutic
      proteins to central nervous system. 

PMID- 24583851
TI  - Anthelmintic activities of aporphine from Nelumbo nucifera Gaertn. cv. Rosa-plena
      against Hymenolepis nana.
AB  - Nelumbo nucifera Gaertn. cv. Rosa-plena (Nelumbonaceae), commonly known as lotus,
      is a perennial aquatic plant grown and consumed throughout Asia. All parts of N.
      nucifera have been used for various medicinal purposes in oriental medicine. From
      the leaves of Nelumbo nucifera Gaertn. cv. Rosa-plena (an aquatic plant),
      liriodenine (1), lysicamine (2), (-)-anonaine (3), (-)-asimilobine (4), (-)
      caaverine (5), (-)-N-methylasimilobine (6), (-)-nuciferine (7), (-)-nornuciferine
      (8), (-)-roemerine (9), 7-hydroxydehydronuciferine (10) and cepharadione B (11)
      were isolated and identification and anthelmintic activities of aporphine was
      evaluated against Anisakis simplex and Hymenolepis nana. This study found that
      the above constituents killed H. nana or reduced their spontaneous movements
      (oscillation/peristalsis). However, the above constituents at various
      concentrations demonstrated no larvicidal effect or ability to halt spontaneous
      parasite movement for 72 h against A. simplex, respectively. In addition,
      according to an assay of cestocidal activity against H. nana and nematocidal
      activity against A. simplex, we found that the above compounds showed greater
      lethal efficacy on H. nana than against A. simplex. Further investigation showed
      that these above constituents have effects against peroxyl radicals under
      cestocidal effect. Together, these findings suggest that these constituents of
      Nelumbo nucifera Gaertn. cv. Rosa-plena might be used as anthelmintic agents
      against H. nana. 

PMID- 24583852
TI  - Assessment of new DFT methods for predicting vibrational spectra and structure of
      cisplatin: which density functional should we choose for studying platinum(II)
      complexes?
AB  - Ten different DFT methods, including several recently developed functionals have
      been tested for their performances in prediction of infrared and Raman spectra
      and molecular structure of cisplatin. The assessed DFT methods cover the range
      from meta-GGA to hybrid, double hybrid and long-range corrected hybrid models
      (M06-L, M06, M06-2X, PBE0, mPW1PW, B3LYP, B2PLYP, CAM-B3LYP, omegaB97XD and LC
      omegaPBE). The calculated structural parameters and theoretical spectra have been
      compared to the corresponding experimental data. It is shown that the LC-omegaPBE
      scheme is superior to other DFT methods in predicting the geometry of cisplatin.
      Unfortunately, the M06-L, M06-2X and B3LYP functionals are deficient in the
      evaluation of the strength of two Pt<-NH3 coordination bonds in cisplatin (the
      calculated bond lengths are too long and the Pt-N stretching frequencies are
      underestimated). Both the PBE0 and mPW1PW functionals, in conjunction with the
      LanL2TZ(f) basis set for Pt give very similar theoretical results and seem to be
      the best methods for predicting the IR and Raman spectra of cisplatin. The long
      range corrected functionals (LC-omegaPBE, omegaB97XD and CAM-B3LYP) have shown
      good performances in predicting the frequencies of Pt-ligand vibrations and are
      promising new tools for theoretical study of novel platinum(II) compounds. 

PMID- 24583855
TI  - Efficacy and safety profile comparison of colistin and tigecycline on the
      extensively drug resistant Acinetobacter baumannii.
AB  - Colistin and tigecycline are the only therapeutic options for extensively drug
      resistant Acinetobacter baumannii (XDR-AB), but there is little comparative
      study. This retrospective observation study evaluated two-colistin and
      tigecycline-antibiotics profiles like treatment success rate, negative conversion
      rate, the length of hospital stay, intensive care unit (ICU) stay and antibiotics
      use, mortality rate during hospital stay and adverse event rate, based on the
      medical record of XDR-AB positive patients who were treated at least 5 d with
      those intravenous antibiotics. Treatment success rate of colistin (n=39) and
      tigecycline (n=16) were not different: 48.7% and 43.8%, respectively (p=0.737),
      though negative conversion rate was significantly higher in the colistin group:
      46.2% against 12.5% (p=0.049). There was no statistically significant difference
      in mortality rate between two groups during hospital stay (43.6% vs. 56.3%,
      p=0.393). There were no significant differences in the following parameters: the
      median length of hospital stay (46.0 d vs. 72.5 d), the median length of
      intensive care units stay (26.0 d vs. 27.0 d), the median length of antibiotics
      use (15.0 d vs. 13.0 d). The colistin group showed serum creatinine elevation
      (defined as elevation more than 2.0 mg/dL and 50% increase from the baseline) as
      43.6% when compared with 12.5% of the tigecycline group (p=0.028). As a
      therapeutic option of XDR-AB, colistin showed significantly better negative
      conversion rate than tigecycline with more frequent nephrotoxic prevalence, and
      treatment success rate and mortality rate were not different from both
      antibiotics groups. 

PMID- 24583854
TI  - Effects of licensed characters on children's taste and snack preferences in
      Guatemala, a low/middle income country.
AB  - BACKGROUND: Marketing of high-energy, low-nutrient foods is one of the
      contributing factors to the obesity-promoting environment. Licensed characters
      are typically used to market these foods to children because they increase brand
      recognition and sales, and data suggest that they affect the taste and snack
      preferences of children in high-income countries, but it has not yet been
      explored in low/middle income countries (LMICs). We sought to examine how
      licensed characters on food packaging influence children's taste and snack
      preferences in Guatemala, a LMIC. METHODS: One hundred twenty-one children (mean
      +/- s.d. age, 7.4 +/- 1.9 years) from four (two preschool and two elementary)
      public schools in Guatemala tasted three food types: potato chips, crackers and
      carrots. Each was presented in two identical packages, except that one had a
      licensed character and the other did not. Children tasted the foods (six total)
      in each package and answered whether they tasted the same or one tasted better.
      Snack preference was also evaluated. RESULTS: Children were significantly
      (P<0.001) more likely to prefer the taste of the foods inside the package with
      the licensed character compared with the one with no character (mean +/- s.d.,
      0.24 +/- 0.54). Most (66%) chose the food in the package with the character for a
      snack. Younger children (P < 0.001) were more likely to prefer the taste of the
      food inside the package with the character. CONCLUSIONS: Licensed characters on
      food packaging influence Guatemalan children's taste and snack preferences. Given
      that these characters are typically used to promote high-energy, low-nutrient
      foods, their influence could contribute toward overconsumption of these foods and
      consequently increased risk of obesity in Guatemalan children. Therefore, public
      health advocates, in Guatemala and elsewhere, might explore restricting the use
      of licensed characters on food packaging as a public health strategy.

PMID- 24583853
TI  - The potential role of leptin in the vascular remodeling associated with obesity.
AB  - BACKGROUND/OBJECTIVES: Extracellular matrix (ECM) participates in the vascular
      remodeling associated with obesity. We investigated the effects of leptin on the
      production of ECM components in primary cultured vascular smooth muscle cells
      (VSMCs) and whether leptin could be a mediator of obesity-induced vascular
      remodeling. METHODS: T he effects of leptin (100 ng ml(-1)) on ECM components and
      superoxide anion production (O(2)(.-)) were evaluated in presence or absence of
      the antioxidant melatonin (10(-)(3) mmol l(-1)) or the inhibitor of
      phosphatidylinositol 3'-kinase (PI3K), LY294002 (2 * 10(-)(4) mmol l(-1)) in
      VSMCs from adult rats in order to explore the role of both oxidative stress and
      the participation of PI3K/Akt pathway in the effects of leptin. ECM components
      and O(2)(.-) were quantified in the aortic media of male Wistar rats fed a high
      fat diet (HFD; 33.5% fat), or a standard diet (CT; 3.5% fat) for 6 weeks.
      RESULTS: In VSMCs, leptin enhanced gene and protein levels of collagen I,
      fibronectin, transforming growth factor (TGF)-beta and connective tissue growth
      factor (CTGF) but did not change those of collagen III and galectin-3. Leptin
      also increased O(2)(.-) and Akt phosphorylation in VSMCs. These effects were
      prevented by the presence of either melatonin or LY294002, except O(2)(.-)
      production in the case of PI3K inhibition. The increase in body weight in HFD
      rats was accompanied by aorta thickening due to an increase in media area. The
      aortic fibrosis observed in HFD rats was associated with high levels of leptin,
      collagen type I, fibronectin, TGF-beta, CTGF, phosphorylated Akt and O(2)(.-).
      Aortic leptin levels were positively correlated with total collagen, collagen I,
      TGF-beta and CTGF levels. No differences were observed in the levels of collagen
      III, elastin or galectin-3 between both the groups. CONCLUSIONS: Leptin could
      participate in the vascular remodeling and stiffness associated with obesity by
      ECM production in VSMCs through the activation of oxidative stress-PI3K/Akt
      pathway and the production of the profibrotic factors TGF-beta and CTGF.

PMID- 24583856
TI  - Caffeic acid reduces cutaneous tumor necrosis factor alpha (TNF-alpha), IL-6 and
      IL-1beta levels and ameliorates skin edema in acute and chronic model of
      cutaneous inflammation in mice.
AB  - Caffeic acid (3,4-dihydroxycinnamic acid, CA) has been reported to have anti
      inflammatory activity in animal models. However, the mechanisms underlying the
      anti-inflammatory effects of CA in skin inflammation are only partially
      understood. The present study was designed to investigate the effects and
      mechanisms of CA on acute and chronic skin inflammation in mice and the effect of
      CA in keratinocytes in vitro. The results showed that topical treatment with CA
      inhibited 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced skin edema in a
      dose-dependent manner, leading to substantial reductions in skin thickness and
      tissue weight, neutrophil-mediated myeloperoxidase activity, and various
      histopathological indicators. The CA treatment also significantly reduced the
      mRNA and protein levels of tumor necrosis factor alpha (TNF-alpha), interleukin-6
      (IL-6) and IL-1beta at the application site, and the TNF-alpha production, the
      TNF-alpha-induced IL-6 and IL-1beta production, and TNF-alpha-induced nuclear
      factor-kappa B (NF-kappaB) activation in human keratinocytes in vitro.
      Furthermore, CA was effective at reducing inflammatory damage induced by chronic
      TPA exposure. These results demonstrate that CA has anti-inflammatory activities
      in both acute and chronic contact dermatitis models via blockade of the mRNA and
      protein synthesis of these cytokines and neutrophil-mediated myeloperoxidase
      activity, and can target inflammatory mediators specifically in the
      keratinocytes. Taken together, the present results suggest that CA might be a
      therapeutic agent against inflammatory skin diseases. 

PMID- 24583857
TI  - Monitoring of gefitinib sensitivity with radioiodinated PHY based on EGFR
      expression.
AB  - Epidermal growth factor receptor (EGFR) is attractive target for tumor diagnosis
      and therapy, as it is specifically and abundantly expressed in tumor cells. EGFR
      tyrosine kinase (TK) inhibitors such as gefitinib and erlotinib are widely used
      in the treatment of non-small cell lung cancer (NSCLC). In this study, we
      investigated whether radioiodinated 4-(3-iodo-phenoxy)-6,7-diethoxy-quinazoline
      (PHY), which is a candidate EGFR-TK imaging agent for single photon emission
      computed tomography (SPECT) is able to predict gefitinib sensitivity. We used
      four NSCLC cell lines-A549 (wild-type EGFR), H1650 (mutant EGFR; del E746_A750),
      H1975 (mutant EGFR; L858R, T790M) and H3255 (mutant EGFR; L858R)-and one
      epidermoid carcinoma cell line, A431 (wild-type EGFR). Cell proliferation assay
      and Western blotting revealed that A431 and H3255 with high EGFR expression
      showed high sensitivity to gefitinib. On the other hand, A549, H1650 and H1975
      showed much lower sensitivity to gefitinib. The blocking study revealed that
      gefitinib decreased tumor uptake in (125)I-PHY in A431-bearing mice. Moreover, in
      vivo tumor uptake of (125)I-PHY was correlated with the IC50 of gefitinib for
      cell proliferation. In the present study, tumor uptake of (125)I-PHY was
      correlated with the gefitinib sensitivity and this uptake was based on expression
      levels of EGFR, but not on mutation status. Although the mutation status is the
      most important factor for predicting gefitinib sensitivity, the abundant
      expression of EGFR is essential for therapy with EGFR-TK inhibitors. Therefore,
      radioiodinated PHY is a potential imaging agent to predict gefitinib sensitivity
      based on EGFR expression levels though further modifications of the imaging agent
      is needed to accurately estimate the mutation status. 

PMID- 24583858
TI  - Glionitrin A, a new diketopiperazine disulfide, activates ATM-ATR-Chk1/2 via
      53BP1 phosphorylation in DU145 cells and shows antitumor effect in xenograft
      model.
AB  - In a recent study, we isolated the diketopiperazine disulfide glionitrin A from
      the co-culture broth of a mine drainage-derived fungus (Aspergillus fumigatus
      KMC901) and bacterium (Sphingomonas KMK001). Here, we investigated the antitumor
      activity of glionitrin A and its underlying molecular mechanisms in human
      prostate cancer DU145 cells. Glionitrin A showed significant cytotoxicity,
      promoting cell cycle arrest and apoptosis. Glionitrin A-treated cells exhibited
      elevated levels of phospho-histone 2AX (Ser139), a marker of DNA damage, and
      accumulated in both S phase and G2/M phase due to the activation of checkpoints
      associated with the ataxia-telangiectasia-mutated and ataxia-telangiectasia
      mutated-Rad3-related Chk1/2 pathway downstream of p53-binding protein 1
      phosphorylation at Ser1778. In addition, glionitrin A induced apoptosis through
      both caspase-dependent and -independent pathways. Glionitrin A activated caspase
      8, -9 and -3 and also released endonuclease G from the mitochondria to the
      nucleus in a dose-dependent manner. Our in vivo study performed in nude mice
      bearing xenografts of DU145 cells showed that glionitrin A dramatically reduced
      the tumor volume by an average of 38.2% (5 mg/kg, per os (p.o.)) and 71.3% (10
      mg/kg, p.o.) at 27 d after the beginning of treatment. Taken together, these
      findings provide a detailed description of the mechanism underlying the
      biological activity of the new natural product glionitrin A, which has the
      potential to be developed as an anti-prostate cancer agent. 

PMID- 24583859
TI  - Chronic administration of bovine milk-derived alpha-lactalbumin improves glucose
      tolerance via enhancement of adiponectin in Goto-Kakizaki rats with type 2
      diabetes.
AB  - Inflammation has been implicated in development of the insulin resistance that
      leads to elevated blood sugar levels associated with type 2 diabetes. It is
      reported that salsalate, a common non-steroidal anti-inflammatory drug, has been
      shown to decrease blood glucose concentration in some clinical study. Recently,
      we found that bovine milk-derived alpha-lactalbumin had anti-inflammatory
      activity caused by inhibiting cyclooxygenase-2. In this study, we investigated
      the effects of chronic administration of alpha-lactalbumin on glucose tolerance
      in Goto-Kakizaki (GK) rats, a model of type 2 diabetes. After 10 weeks
      administration of the alpha-lactalbumin (300 mg/kg, twice a day), oral glucose
      tolerance tests revealed significant decrements of blood glucose levels after
      glucose loading. However, significant differences of insulin levels were not
      observed among three GK rats groups after glucose loading. alpha-Lactalbumin
      treatment enhanced high molecular weight form of adiponectin and suppressed
      prostaglandin E2 levels in plasma. These results suggest that alpha-lactalbumin
      effectively decreased blood glucose levels after glucose loading in GK rat, and
      the decrements may be due to enhancement of adiponectin. 

PMID- 24583860
TI  - Adhesion of enterohemorrhagic Escherichia coli O157:H7 to the intestinal
      epithelia is essential for inducing secretory IgA antibody production in the
      intestine of mice.
AB  - We examined whether adherence of enterohemorrhagic Escherichia coli (EHEC)
      O157:H7 to intestinal epithelial cells contributed to the induction of secretory
      immunoglobulin A (IgA) antibody production in mice. Wild-type EHEC O157:H7 and
      its mutants deficient in the espA, sepL, tir and eae genes, encoding adherent
      factors on the locus of enterocyte effacement (LEE), were inoculated
      intragastrically into mice. Inoculation of wild-type EHEC induced fecal IgA
      antibodies specific to EHEC at 4 weeks after the inoculation, but that of espA-
      and sepL-deletion mutants did not. Furthermore, even 4 inoculations at weekly
      intervals with espA-deletion mutant, heat-killed wild-type EHEC and nonpathogenic
      E. coli did not induce fecal IgA antibodies, although these bacterial
      inoculations induced serum antibodies. Kanamycin (Km)-treated mice showed
      prolonged and similar fecal shedding of Km-resistant mutants of EHEC O157:H7
      including A2-F6 having intact LEE, A6-E7 (sepL-insertion mutant), G1-E11 (tir
      insertion mutant) and Deltaeae (eae-deletion mutant). In this case, A2-F6 induced
      fecal IgA antibodies, but the other mutants with defective LEE did not. In
      contrast to the fecal IgA antibodies, serum IgM and IgG antibodies were induced
      in mice inoculated with any of the LEE defective mutants as well as A2-F6. Thus,
      adhesion of EHEC to epithelial cells is essential for inducing the mucosal immune
      response in the intestine but not for inducing the systemic immune response. 

PMID- 24583861
TI  - Protective effect of SUN N8075, a free radical scavenger, against excessive light
      induced retinal damage in mice.
AB  - Although dry age-related macular degeneration (AMD) is one of the major causes of
      blindness, no effective therapies are developed. In this study, we investigated
      the effects of SUN N8075, a radical scavenger with neuroprotective properties,
      against light-induced retinal damage used as the model of dry AMD in mice. After
      dark adaption for 24 h, we exposed the mice at 8000 lx for 3 h. We evaluated the
      retinal damage by recording the electroretinagram (ERG) and measuring the
      thickness of outer nuclear layer (ONL) at 5 d after the light exposure. Retinal
      apoptotic cells were also detected by terminal deoxynucleotidyl transeferase
      mediated deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL) staining, and
      the expression of 8-hydroxy-2-deoxyguanosine (8-OHdG) as an index for oxidative
      stress at 48 h after exposure to light. In ERG measurement, the intraperitoneal
      administration of SUN N8075 at 30 mg/kg improved the retinal dysfunction induced
      by the excess light exposure. In the histological evaluation, SUN N8075 inhibited
      the reduction of ONL thickness. In addition, SUN N8075 decreased in both numbers
      of TUNEL- and 8-OHdG-positive cells in ONL. These findings suggest that the
      systemic administration of SUN N8075 has protective effects on excess light
      induced photoreceptor degeneration, via inhibition of oxidative stress. 

PMID- 24583862
TI  - Stereoselective transport of human His27- and Arg27-reduced folate carrier.
AB  - The stereoselective transport of methotrexate (L-amethopterin, L-MTX) and its
      antipode (D-amethopterin, D-MTX) by human reduced folate carrier (hRFC) has been
      examined in HEK293 cells expressing H27-hRFC and R27-hRFC. The uptake of both L
      MTX and D-MTX increased as the extracellular pH increased from 6.0 to 7.4. The
      initial uptake rate of L-MTX into the H27- and R27-hRFCs of the HEK293 cells
      followed Michaelis-Menten kinetics with Km values of approximately 0.24 and 0.47
      uM, respectively. Dixon plots revealed that the [(3)H]-L-MTX uptake mediated by
      the H27- and R27-hRFCs was inhibited competitively by unlabeled L-MTX with Ki
      values of approximately 0.1 and 0.5 uM, respectively. D-MTX also competitively
      inhibited the H27- and R27-hRFC mediated uptake of [(3)H]-L-MTX with Ki values of
      approximately 3.4 and 3.2 uM, respectively. The RFC-mediated uptake clearance of
      L-MTX was approximately 15-fold greater than that of D-MTX in the H27-hRFC-HEK293
      cells, and was more than 30-fold greater than that of D-MTX in the R27-hRFC
      HEK293 cells. The results of the current study have revealed that the enantiomers
      of MTX enantiomers can be transported in a stereoselective manner by the H27- and
      R27-hRFCs because of significant differences in the affinities of the enantiomers
      to the hRFC. 

PMID- 24583863
TI  - Improvements of doxorubicin-induced antitumor activity and adverse reaction by
      combined citrulline.
AB  - Citrulline is an amino acid with antioxidant activity. In this study, effects of
      citrulline on the adverse effects of doxorubicin (DOX) and DOX-induced antitumor
      activity were examined. Citrulline significantly inhibited DOX-induced increases
      in lipid peroxide (LPO) in the heart as adverse reaction. Combined treatment with
      DOX and citrulline increased DOX levels in tumor cells and enhanced cytotoxicity
      in vitro by significantly increasing DOX uptake compared with DOX treatment
      alone. In simultaneous in vivo treatments, combination treatment with DOX and
      citrulline decreased tumor weight and increased DOX concentrations in tumors.
      Promotion of DOX uptake by citrulline enhanced the antitumor activity of DOX
      through the action of energy-independent and Na(+)-independent transporters. This
      effect of citrulline on DOX influx is identical to that of S-(4-nitrobenzyl)-6
      thioinosine, promoting DOX influx through the equilibrative nucleoside
      transporter 1. Therefore, it is anticipated that citrulline as a food component
      may enhance DOX efficacy. 

PMID- 24583864
TI  - Evaluation of the botanical origin of black cohosh products by genetic and
      chemical analyses.
AB  - Despite the increasing sales of black cohosh (the dried rhizome and root of
      Cimicifuga racemosa L.) in the world herbal market, these products have
      continuous adulteration issues. The botanical authenticity of the black cohosh
      products is the first important step for ensuring their quality, safety and
      efficacy. In this study, we genetically identified the botanical sources of 10
      black cohosh products and 5 Cimicifuga Rhizome crude drugs of Japanese
      Pharmacopoeia grade, and analyzed the metabolic profiling of 25 black cohosh
      products using liquid chromatography-tandem mass spectrometry (LC-MS/MS).
      Consequently, we found that C. dahurica and possibly C. foetida are misused as
      sources of the black cohosh products and in some cases, the extracts of black
      cohosh were adulterated with the plant materials of C. dahurica. We demonstrated
      that these three species can be distinguished by three marker compounds in a
      specific mass range. These results must be helpful in establishing regulations
      for the safe use of the black cohosh products. 

PMID- 24583865
TI  - Endothelin-1 receptors in rat tissues: characterization by bosentan, ambrisentan
      and CI-1020.
AB  - The present study aimed to characterize comparatively endothelin-1 (ET-1)
      receptors in rat tissues by radioligand binding assay using [(125)I]ET-1 and to
      examine receptor binding after oral administration of bosentan. Significant
      amount of specific [(125)I]ET-1 binding was detected in the lung, heart, kidney,
      bladder and cerebral cortex of rats. ET-1, bosentan, ambrisentan, and CI-1020
      inhibited specific [(125)I]ET-1 binding in these tissues in a concentration
      dependent manner. The Hill coefficients of each agent in the rat lung and
      cerebral cortex and those of bosentan and ET-1 in the heart, kidney and bladder
      were close to unity, while the Hill coefficients of ambrisentan and CI-1020 in
      the heart, kidney and bladder were less than one. The nonlinear least squares
      regression analysis revealed the presence of high- and low-affinity ET-1 receptor
      sites in these tissues for ambrisentan and CI-1020. Oral administration of
      bosentan caused a dose-dependent decrease in specific [(125)I]ET-1 binding in the
      rat lung, kidney and bladder, suggesting significant binding of the tissue ET-1
      receptors in vivo. In conclusion, it has been shown that a significant amount of
      pharmacologically relevant ET-1 receptors may exist in rat tissues and that ET-1
      receptor antagonists such as bosentan at pharmacological doses may exert some
      pharmacological effects by binding these ET-1 receptors. 

PMID- 24583866
TI  - Development of irreversible inactivators of spermine oxidase and N1
      acetylpolyamine oxidase.
AB  - Three functional groups (2-propenyl, 2-propynyl, and 2,3-butadienyl) were
      introduced onto one of the terminal amino groups of spermidine. Of the six
      compounds synthesized, N-(3-aminopropyl)-N'-2,3-butadienyl-1,4-butanediamine
      (N(8)-butadienyl Spd) and N-[3-(2,3-butadienylamino)propyl]-1,4-butanediamine
      (N(1)-butadienyl Spd) irreversibly inactivated human spermine oxidase (SMO) and
      N(1)-acetylpolyamine oxidase (APAO). Interestingly, N(8)-butadienyl Spd
      inactivated SMO far more potently than N,N'-di-2,3-butadienyl-1,4-butanediamine
      (MDL 72527). 

PMID- 24583867
TI  - Specificity of Fur binding to the oxidative stress response gene promoter in the
      facultative anaerobic archaeon Thermoplasma volcanium.
AB  - The genome of the facultative anaerobic thermoacidophilic archaeon Thermoplasma
      volcanium contains the open-reading frames (ORFs) tvsod and tvogg, which are
      predicted to encode a putative superoxide dismutase and an 8-oxoguanine DNA
      glycosylase, respectively. Tvsod is immediately upstream of tvogg, and these two
      ORFs are aligned in a head-to-tail manner in a single operon. A previous study
      showed that T. volcanium contains an ORF (TVN0292) encoding the ferric uptake
      regulator (Fur) and that the T. volcanium Fur protein (TvFur) binds to its own
      promoter in a metal-dependent manner in vitro. Here, we demonstrated that TvFur
      also binds to the tvsod-tvogg promoter and determined the TvFur-binding sequences
      in the tvsod-tvogg promoter by DNaseI footprinting analysis. These results
      suggest that Fur is required for resistance against reactive oxygen species in
      this facultative anaerobic archaeon. 

PMID- 24583868
TI  - Effects of oils and emulsifiers on the skin penetration of stearyl
      glycyrrhetinate in oil-in-water emulsions.
AB  - We investigated whether an emulsifier or an emulsified oil affects the skin
      penetration of stearyl glycyrrhetinate (SG) when it is applied in an oil-in-water
      (O/W)-type emulsion under finite dose conditions in vitro. SG has a high
      molecular weight (MW: 723) and high lipophilicity (log P: 15.6). Skin penetration
      of SG applied with O/W emulsions was evaluated using 6 types of emulsifiers that
      are commonly used in cosmetics; however, no significant differences were observed
      between these emulsifiers. When applied with liquid paraffins in oil phase, SG
      skin penetration increased significantly as the molecular weight of the liquid
      paraffin decreased. The skin penetration of the fluorescent dye 1,1'-dioctadecyl
      3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI; MW: 834, log P: 23.2)
      also increased with O/W-type emulsions containing liquid paraffins of lower
      molecular weights. These results indicate that use of O/W-type emulsions with an
      appropriate oil phase can improve SG skin penetration. 

PMID- 24583869
TI  - Immunoprotective effect of epigallocatechin-3-gallate on oral anticancer drug
      induced alpha-defensin reduction in Caco-2 cells.
AB  - The aim of this study was to determine the effect of interaction between tegafur
      (FT) and epigallocatechin-3-gallate (EGCG) on the expression of alpha-defensins
      (HD-5: human alpha-defensin 5, HD-6: human alpha-defensin 6) by using a Caco-2
      cell line as a model of human intestinal epithelial cells. This is the first
      study in which the effect of interaction of an oral anticancer drug and
      functional food on the innate immune system was examined. alpha-Defensins are
      abundant constituents of mouse and human paneth cells and play a role in the
      innate immune system in intestine. We detected HD-5 and HD-6 mRNA in Caco-2 cells
      and evaluated the effects of FT and EGCG on these mRNA levels. HD-5 and HD-6 mRNA
      levels were decreased by exposure to FT. Production of reactive oxygen species
      (ROS) was induced by exposure to FT as well as H2O2 exposure, and EGCG suppressed
      FT-induced production of ROS. Furthermore, FT-induced decrease in HD-5 and HD-6
      mRNA levels was almost completely suppressed by EGCG. These results indicate that
      EGCG restored the decrease of alpha-defensins induced by FT at the
      transcriptional level in Caco-2 cells, suggesting that EGCG can be used as
      adjunctive therapy in chemotherapy. 

PMID- 24583870
TI  - Effect of the hot water extract of Artocarpus camansi leaves on 2,4,6
      trinitrochlorobenzene (TNCB)-induced contact hypersensitivity in mice.
AB  - Medicinal plants with reported anti-inflammatory activity could have the
      potential use as anti-allergens and inhibitors of allergic contact dermatitis
      reactions produced by allergens and chemicals. Some species from the genus
      Artocarpus were reported to have anti-inflammatory activity. In the Philippines
      one local source is Artocarpus camansi BLANCO (Moraceae), which is utilized as an
      ingredient of their cuisine, and decoction of leaves is used for diabetes and
      baths of people with rheumatism. The objective of this study was to evaluate the
      effect of the hot water extract of A. camansi leaves on contact hypersensitivity
      (CHS) in mice. Contact hypersensitivity was induced using 2,4,6
      trinitrochlorobenzene (TNCB). The results showed that the A. camansi hot water
      extract exhibited significant activity against the swelling produced during 24 h
      and 48 h post-challenge. The same responses were observed from the mice that
      received the kamansi ethanol-precipitate (KEP) and kamansi ethanol precipitate
      water-soluble (KEPWS) fractions. Since the high molecular mass fraction showed
      the significant activity, we therefore speculate that the compound responsible
      might be a polysaccharide and/or glycoprotein. In conclusion, our results suggest
      that the hot water extract of A. camansi leaves might be an effective natural
      product to treat allergic contact dermatitis. However, further investigations are
      required to understand the mechanisms involved. 

PMID- 24583871
TI  - Therapeutic effects of cationic hybrid liposomes on the hepatic metastasis of
      colon carcinoma along with apoptosis in vivo.
AB  - Therapeutic effects of cationic hybrid liposomes (HL) composed of 87 mol%
      dimyristoyl-phosphatidylcholine (DMPC), 5 mol% polyoxyethylene (21) dodecyl ether
      (C12(EO)21) and 8 mol% O,O'-ditetradecanoyl-N-(alpha-trimethyl-ammonioacetyl)
      diethanolamine chloride (2C14ECl) on the metastasis of human colon carcinoma
      (HCT116) cells were examined in vivo. Cationic HL having a hydrodynamic diameter
      less than 150 nm were preserved for one month. Therapeutic effects were obtained
      in the hepatic metastasis mouse models of HCT116 cells after the intravenous
      injection of cationic HL. The histological analysis indicated the induction of
      apoptosis in the liver section of the hepatic metastasis mouse models treated
      with cationic HL in vivo. Therapeutic effects of cationic HL without any drugs on
      the hepatic metastasis were revealed for the first time on the basis of
      histological analyses in vivo. 

PMID- 24583872
TI  - Acute-on-chronic liver failure: a new clinical entity.
AB  - Patients hospitalized for an acute complication of cirrhosis who also have organ
      failure(s) are at high risk of short-term death. The term acute-on-chronic liver
      failure (ACLF) is used to characterize these patients. Until recently, there was
      no evidence-based definition of ACLF. The results of a large prospective
      observational European study called Chronic Liver Failure Consortium Acute-on
      Chronic Liver Failure in Cirrhosis study were published in 2013 establishing
      diagnostic criteria for ACLF in a large series of hospitalized patients who had
      an acute complication of cirrhosis. In addition, this study described the natural
      history of ACLF. According to the Acute-on-Chronic Liver Failure in Cirrhosis
      study, ACLF is now considered a new clinical entity because it is distinct from
      traditional decompensated cirrhosis, based not only on the presence of organ
      failure(s) and high mortality rate but also on younger age, alcoholic etiology of
      cirrhosis, higher prevalence of some precipitating events (bacterial infections,
      active alcoholism), and higher level of systemic inflammation. ACLF is a new
      entity also because it cannot be explained entirely by severe sepsis or severe
      alcoholic hepatitis; a large proportion of cases are of unknown origin. ACLF
      should be considered as a whole that includes subcategories such as severe
      sepsis, severe alcoholic hepatitis, and others, which have yet to be defined.
      ACLF is a relatively common syndrome because it occurs in 31% of hospitalized
      patients with cirrhosis who have an acute complication of their liver disease. In
      these patients, ACLF is the most common cause of death. 

PMID- 24583873
TI  - Development of an enzyme-linked immunosorbent assay based on anti-puerarin
      monoclonal antibody and its applications.
AB  - An enzyme-linked immunosorbent assay (ELISA) was developed, and its application
      in immunoaffinity column chromatography was studied using a monoclonal antibody
      (MAb) against puerarin. Splenocytes isolated from a female BALB/c mouse immunised
      with a puerarin-bovine serum albumin (BSA) conjugate were fused with SP2/0
      myeloma cells. The hybridoma cell line secreting MAb against puerarin (AA9) was
      acquired by screening and limiting dilution. The antibody generated was highly
      specific for puerarin with <0.01% cross-reactivity with over 50 structurally
      related chemicals, except for baicalein (51.8%). Using AA9, we developed an
      immunoassay for puerarin with a linear detection range of 10ng/ml to 1MUg/ml.
      This assay system was further validated using intra- and inter-assays and
      recovery experiments. In addition, puerarin levels in both formulated Chinese
      medicines and biological samples were determined with high sensitivity and
      efficiency. Finally, we developed and validated protocols for knocking puerarin
      out of its parent medicine completely. In conclusion, we successfully developed a
      reliable ELISA and an immunoaffinity column for puerarin detection and knockout,
      which are useful tools for exploring the role of puerarin in formulated Chinese
      medicines. 

PMID- 24583874
TI  - mTORC2 dictates Warburg effect and drug resistance.

PMID- 24583875
TI  - Applying ecological modeling to parenting for Australian refugee families.
AB  - Children in families with parents from refugee backgrounds are often viewed as a
      vulnerable group with increased risks of developing physical or psychological
      problems. However, there is very little research regarding the strategies that
      parents might use to parent their children in a new country while they also
      manage the interrelated challenges of poverty, social isolation, maternal stress,
      and mental ill health that often go along with resettlement. We explore the
      application of ecological modeling, specifically at individual, institutional,
      and policy levels, within an Australian context to critique the factors that
      shape the development of parenting capacity within refugee families settling in a
      new Western country. Ecological modeling enables examination of how public policy
      at local state and national levels influences the individual and family directly
      and through the organizations that are given the task of implementing many of the
      policy recommendations. Recommendations for health practice and research are
      made. 

PMID- 24583876
TI  - The effects of an instructional intervention on racial attitude formation in
      occupational therapy students.
AB  - The purpose of this pilot study was to examine the effect of a 9-week
      instructional intervention designed to increase 24 Caucasian American
      occupational therapy students' awareness of personal racial attitudes toward
      African Americans. The learning content focused on specific cognitive-perceptual
      biases thought to play a role in the formation of racial attitudes. A pre- to
      posttest implicit measure of racial bias indicated an increase in bias in some
      students following the intervention and a decrease of bias in others. Students'
      perception of the instruction and subsequent stereotype activation are discussed
      as possible moderators of the intervention's effectiveness. Several implications
      for future instruction and research are suggested to address factors that may
      limit antibias instruction. 

PMID- 24583877
TI  - One woman's empowerment is another's oppression: Korean migrant mothers on giving
      birth in Aotearoa New Zealand.
AB  - PURPOSE: To critically analyze the power relations underpinning New Zealand
      maternity, through analysis of discourses used by Korean migrant mothers. DESIGN:
      Data from a focus group with Korean new mothers was subjected to a secondary
      analysis using a discourse analysis drawing on postcolonial feminist and
      Foucauldian theoretical ideas. RESULTS: Korean mothers in the study framed the
      maternal body as an at-risk body, which meant that they struggled to fit into the
      local discursive landscape of maternity as empowering. They described feeling
      silenced, unrecognized, and uncared for. DISCUSSION AND CONCLUSIONS: The Korean
      mothers' culturally different beliefs and practices were not incorporated into
      their care. They were interpellated into understanding themselves as problematic
      and othered, evidenced in their take up of marginalized discourses. IMPLICATIONS
      FOR PRACTICE: Providing culturally safe services in maternity requires
      considering their affects on culturally different women and expanding the
      discourses that are available.

PMID- 24583878
TI  - c-Kit immunoexpression delineates a putative endothelial progenitor cell
      population in developing human lungs.
AB  - Expression of c-Kit and its ligand, stem cell factor (SCF), in developing human
      lung tissue was investigated by immunohistochemistry. Twenty-eight human fetal
      lungs [age range 13 to 38 gestational wk (GW)] and 12 postnatal lungs (age range
      1-79 yr) were evaluated. We identified c-Kit(+) cells in the lung mesenchyme as
      early as 13 GW. These mesenchymal c-Kit(+) cells in the lung did not express mast
      cell tryptase or alpha-smooth muscle actin. However, these cells did express
      CD34, VEGFR2, and Tie-2, indicating their endothelial lineage. Three-dimensional
      reconstructions of confocal laser scanning images revealed that c-Kit(+) cells
      displayed a closed-end tube formation that did not contain hematopoietic cells.
      From the pseudoglandular phase to the canalicular phase, c-Kit(+) cells appeared
      to continuously proliferate, to connect with central pulmonary vessels, and
      finally, to develop the lung capillary plexus. The spatial distribution of c-Kit-
      and SCF-positive cells was also demonstrated, and these cells were shown to be in
      close association. Our results suggest that c-Kit expression in early fetal lungs
      marks a progenitor population that is restricted to endothelial lineage. This
      study also suggests the potential involvement of c-Kit signaling in lung vascular
      development.

PMID- 24583880
TI  - Polyolefin backbone substitution in binders for low temperature powder injection
      moulding feedstocks.
AB  - This paper reports the substitution of polyolefin backbone binder components with
      low melting temperature carnauba wax for powder injection moulding applications.
      The effect of various binder compositions of Al2O3 feedstock on thermal
      degradation parameters is investigated by thermogravimetric analysis. Within the
      experimental framework 29 original feedstock compositions were prepared and the
      superiority of carnauba wax over the polyethylene binder backbone was
      demonstrated in compositions containing polyethylene glycol as the initial
      opening agent and governing the proper mechanism of the degradation process.
      Moreover, the replacement of synthetic polymer by the natural wax contributes to
      an increase of environmental sustainability of modern industrial technologies.

PMID- 24583879
TI  - Bleomycin delivery by osmotic minipump: similarity to human scleroderma
      interstitial lung disease.
AB  - The interstitial lung diseases (ILD) include a large number of chronic,
      progressive, irreversible respiratory disorders involving pulmonary fibrosis, the
      most common of which are idiopathic pulmonary fibrosis and scleroderma lung
      disease (SSc ILD). Because bleomycin causes lung fibrosis when used in cancer
      chemotherapy, it is used to model human ILD in rodents. In most studies,
      bleomycin has been delivered directly into the lung by intratracheal or intraoral
      administration. Here we have compared the effects in mice of bleomycin delivered
      directly into the lungs (direct model) or systemically using osmotic minipumps
      (pump model) to determine which more closely resembles human ILD. The pump model
      is more similar to human SSc ILD in that: 1) lung injury/fibrosis is limited to
      the subpleural portion of the lung in the pump model and in SSc ILD, whereas the
      entire lung is affected in the direct model; 2) conversely, there is massive
      inflammation throughout the lung in the direct model, whereas inflammation is
      limited in the pump model and in SSc ILD; 3) hypertrophic type II alveolar
      epithelial cells are present at high levels in SSc ILD and in the pump model but
      not in the direct model; and 4) lung fibrosis is accompanied by dermal fibrosis.
      The pump model is also move convenient and humane than the direct model because
      there is less weight loss and mortality. 

PMID- 24583881
TI  - Biomolecule-mediated synthesis of selenium nanoparticles using dried Vitis
      vinifera (raisin) extract.
AB  - Biomolecule-mediated nanoparticle synthesis has recently the gained attention of
      researchers due to its ecofriendly and non-toxic nature. Metabolites from plant
      extracts represent a better alternative to chemical methods to fulfill the
      growing demand for non-hazardous nanoparticle synthesis routes. Selenium and its
      nanoparticles have an extensive range of applications. Thus, biofabrication of
      selenium nanoparticles can be potentially useful in various fields. This study
      reports a green approach to biosynthesize selenium nanoparticles (Se-np) using
      dried Vitis vinifera (raisin) extracts. The biosynthesized selenium nanoparticles
      were characterized using transmission electron microscope (TEM), dynamic light
      scattering (DLS), X-ray diffraction (XRD), energy dispersive X-ray (EDX)
      spectroscopy and Fourier transform infrared spectroscopy (FTIR). Transmission
      electron microscopic images revealed the spherical shape of biosynthesized
      selenium nanoparticles and a size range of 3-18 nm. Dynamic light scattering also
      confirmed the average particle size of 8.12 +/- 2.5 nm with 0.212 PDI. The
      crystalline nature of selenium nanoparticles was confirmed by the X-ray
      diffraction study. Moreover, as inferred from the FTIR spectrum, the presence of
      highly stable lignin biopolymer on the surface of selenium nanoballs suggests a
      possible role as capping agent. 

PMID- 24583882
TI  - Revising the scope of practice for oral health professionals: enter genomics.

PMID- 24583883
TI  - Hepatitis B.

PMID- 24583884
TI  - Authors' response.

PMID- 24583885
TI  - Unnecessary treatment.

PMID- 24583886
TI  - Suspicious treatment plan.

PMID- 24583887
TI  - Authors' response.

PMID- 24583888
TI  - Treating patients with traumatic life experiences: providing trauma-informed
      care.
AB  - BACKGROUND: and Overview Dentists frequently treat patients who have a history of
      traumatic events. These traumatic events (including childhood sexual abuse,
      domestic violence, elder abuse and combat history) may influence how patients
      experience oral health care and may interfere with patients' engagement in
      preventive care. The purpose of this article is to provide a framework for how
      dentists can interact sensitively with patients who have survived traumatic
      events. CONCLUSIONS: The authors propose the trauma-informed care pyramid to help
      engage traumatized patients in oral health care. Evidence indicates that all of
      the following play an important role in treating traumatized patients:
      demonstrating strong behavioral and communication skills, understanding the
      health effects of trauma, engaging in interprofessional collaboration,
      understanding the provider's own trauma-related experiences and understanding
      when trauma screening should be used in oral health practice. PRACTICAL
      IMPLICATIONS: Dental patients with a history of traumatic experiences are more
      likely to engage in negative health habits and to display fear of routine dental
      care. Although not all patients disclose a trauma history to their dentists, some
      patients might. The trauma-informed care pyramid provides a framework to guide
      dental care providers in interactions with many types of traumatized patients,
      including those who choose not to disclose their trauma history in the context of
      oral health care.

PMID- 24583889
TI  - The accuracy of diagnostic tests for adenoid hypertrophy: a systematic review.
AB  - BACKGROUND: Adenoid hypertrophy may cause sleep-disordered breathing and altered
      craniofacial growth. The authors conducted a study to gauge the accuracy of
      alternative tests compared with nasoendoscopy (reference standard) for screening
      adenoid hypertrophy. METHODS: The authors conducted a systematic review that
      included searches of electronic databases, hand searches of bibliographies of
      relevant articles and gray literature searches. They included all articles in
      which an alternative test was compared with nasoendoscopy in children with
      suspected nasal or nasopharyngeal airway obstruction. RESULTS: The authors
      identified seven articles that were of poor to good quality. They identified the
      following alternative tests: multirow detector computed tomography (sensitivity,
      92 percent; specificity, 97 percent), videofluoroscopy (sensitivity, 100 percent;
      specificity, 90 percent), rhinomanometry with decongestant (sensitivity, 83
      percent; specificity, 83 percent) and clinical examination (sensitivity, 22
      percent; specificity, 88 percent). Lateral cephalograms tended to have good to
      fair sensitivity (typically 61-75 percent) and poor specificity (41-55 percent)
      when adenoid size was evaluated but excellent to good specificity when airway
      patency was evaluated (68-96 percent). CONCLUSIONS: No ideal tool exists for
      dentists to screen adenoid hypertrophy, owing to access constraints, radiation
      concerns and suboptimal diagnostic accuracy. Research is needed to identify a low
      risk, easily acceptable, highly valid diagnostic screening tool. PRACTICAL
      IMPLICATIONS: Although lateral cephalograms (which have good to fair sensitivity)
      and a thorough medical history (which has good specificity) are imperfect
      individually, when they are used together, they can compensate for each others
      weaknesses. This combined approach is the best tool available to dentists for
      screening adenoid hypertrophy.

PMID- 24583890
TI  - Potential diversion of local anesthetics from dental offices for use as cocaine
      adulterants.
AB  - BACKGROUND: Reports of lidocaine and benzocaine in the bloodstreams of people who
      abuse cocaine with accompanying reports of seizures and methemoglobinemia
      indicate that there is a potential that local anesthetics are being diverted from
      dental offices and being used as cocaine adulterants. These adulterants augment
      the nasal numbness produced by inhaling cocaine. METHODS: The authors conducted a
      PubMed search by using the following terms: "adulterants," "benzocaine,"
      "cocaine," "lidocaine" and "methemoglobinemia." RESULTS: The authors identified
      two case reports as a result of their PubMed search. Each case involved a patient
      with symptoms of both cocaine overdose and methemoglobinemia who sought treatment
      at an emergency department. The results of urine samples from each patient, as
      well as the results from an analysis of a sample of one patient's cocaine,
      revealed the presence of many adulterants, including lidocaine and benzocaine.
      CONCLUSIONS: Injectable lidocaine and topical benzocaine are cheap and readily
      available substances found in dental offices that may be diverted by anyone
      including dentists, office staff members or patients-to adulterate cocaine.
      PRACTICAL IMPLICATIONS: Additional research is needed to identify whether dental
      offices are a common source of cocaine adulterants. The authors recommend that
      dentists keep track of their local anesthetic supplies.

PMID- 24583891
TI  - The inferior alveolar nerve's loop at the mental foramen and its implications for
      surgery.
AB  - BACKGROUND: In this study, the authors aimed to identify and measure the anterior
      extension of the alveolar loop (aAL) and the caudal extension of the alveolar
      loop (cAL) of the inferior alveolar nerve by using cone-beam computed tomography
      (CBCT). They also aimed to provide recommendations for surgery in the anterior
      mandible. METHODS: In this retrospective case study of the frequency and
      extension of aAL and cAL, the authors evaluated 1,384 mandibular sites in 694
      CBCT scans of dentate and partly edentulous patients, performed mainly for
      further diagnosis before removal of the mandibular third molars between January
      2009 and February 2013, by using multiplanar reconstructions. RESULTS: The
      frequency of aAL was 69.73 percent and of cAL was 100 percent. The mean value for
      aAL was 1.16 millimeters, with a range of 0.3 to 5.6 mm; the mean value for cAL
      was 4.11 mm, with a range of 0.25 to 8.87 mm. For aAL, 95.81 percent of the sites
      showed values of 0 to 3 mm; for cAL, 93.78 percent of the sites showed values of
      0.25 to 6 mm. Dentate patients showed statistically significantly higher values
      for cAL than did partly edentulous patients (P = .043). CBCT resolution had a
      statistically significant impact on cAL measurements (P = .001), with higher
      values at higher resolution. CONCLUSIONS: This study showed a high frequency of
      and large variations in aAL and cAL. In contrast to panoramic radiography, CBCT
      has been shown to be a reliable tool for identifying and measuring the AL.
      Therefore, preoperative diagnosis with CBCT is recommended for planning three
      dimensional tasks such as implant placement in the vicinity of the mental
      foramen. PRACTICAL IMPLICATIONS: Owing to the variability of aAL and cAL
      measurements, it is difficult to recommend reliable safety margins for surgical
      procedures such as implant placement, bone harvesting or genioplasty Depending on
      the indication, the clinician should consider preoperative diagnosis by means of
      CBCT.

PMID- 24583892
TI  - Persistent pain after endodontic therapy.

PMID- 24583893
TI  - Facial asymmetry associated with a mixed radiolucent-radiopaque change of the
      maxillofacial bones.

PMID- 24583894
TI  - There is no one mandibular advancement device design that fits all for the
      management of obstructive sleep apnea.

PMID- 24583895
TI  - Survival of various tooth- or implant-supported restorations.

PMID- 24583897
TI  - Succeeding as a new dentist.

PMID- 24583899
TI  - For the patient: Medical identity theft: how to protect yourself.

PMID- 24583900
TI  - Reference dosimetry on TomoTherapy: an addendum to the 1990 UK MV dosimetry code
      of practice.
AB  - The current UK code of practice for high-energy photon therapy dosimetry
      (Lillicrap et al 1990 Phys. Med. Biol. 35 1355-60) gives instructions for
      measuring absorbed dose to water under reference conditions for megavoltage
      photons. The reference conditions and the index used to specify beam quality
      require that a machine be able to set a 10 cm * 10 cm field at the point of
      measurement. TomoTherapy machines have a maximum collimator setting of 5 cm * 40
      cm at a source to axis distance of 85 cm, making it impossible for users of these
      machines to follow the code. This addendum addresses the specification of
      reference irradiation geometries, the choice of ionization chambers and the
      determination of dosimetry corrections, the derivation of absorbed dose to water
      calibration factors and choice of appropriate chamber correction factors, for
      carrying out reference dosimetry measurements on TomoTherapy machines. The
      preferred secondary standard chamber remains the NE2611 chamber, which with its
      associated secondary standard electrometer, is calibrated at the NPL through the
      standard calibration service for MV photon beams produced on linear accelerators
      with conventional flattening filters. Procedures are given for the derivation of
      a beam quality index specific to the TomoTherapy beam that can be used in the
      determination of a calibration coefficient for the secondary standard chamber
      from its calibration certificate provided by the NPL. The recommended method of
      transfer from secondary standard to field instrument is in a static beam, at a
      depth of 5 cm, by sequential substitution or by simultaneous side by side
      irradiation in either a water phantom or a water-equivalent solid phantom.
      Guidance is given on the use of a field instrument in reference fields.

PMID- 24583901
TI  - The measurement of 3-epimer 25-hydroxyvitamin D by mass spectrometry in clinical
      specimens detects inconsequential levels in adult subjects.
AB  - BACKGROUND: Vitamin D is derived from dietary sources or from the action of
      ultraviolet light on 7-dehydrocholesterol and undergoes a number of enzymatic
      modifications that lead to the synthesis of active vitamin D metabolites or
      metabolites with reduced biological activity. Among these, epimerization at the 3
      hydroxyl group leads to the synthesis of 3-epimer 25-hydroxyvitamin D (3EVD).
      Described first in biological system experiments using in vitro incubation of
      vitamin D in cell culture, this molecule has been reported as having distinct
      activities when compared with 25-hydroxy vitamin D (25OHVD). Measurements of
      vitamin D have been conducted using a variety of methodologies and have led to
      conflicting assessments of the quantities of 3EVD3 that are measured. METHOD: The
      present article describes the development and use of a simple liquid
      chromatography-tandem mass spectrometry method validated by the Clinical
      Laboratory Improvement Amendments to quantitate 3EVD3 in 3528 subjects, including
      309 children (162 are <2 years) and 232 pregnant women. RESULTS: Our findings
      demonstrate that, although 3EVD3 constitutes a significant proportion of
      measureable 25OHVD3 in subjects younger than 1 year, 3EVD3 levels are negligible
      in most subjects older than 1 year. CONCLUSIONS: It is important to choose the
      correct 25OHVD assay dependent on the age of the patient. Patients younger than 1
      year should be run on a liquid chromatography-tandem mass spectrometry assay
      proven to not have potential contributions from any 3EVD present in the sample.

PMID- 24583902
TI  - Asthma and obstructive sleep apnea: clinical and pathogenic interactions.
AB  - Asthma and obstructive sleep apnea (OSA) are among the most prevalent chronic
      human diseases of the 21st century. They share several risk and aggravating
      factors such as obesity, smoking, gastroesophageal reflux, sinonasal disease or
      upper airway involvement, systemic inflammation, etc. Although the association
      between OSA and chronic obstructive pulmonary disease or "overlap syndrome" is
      better known and characterized, the association of asthma and OSA or "alternative
      overlap syndrome" is less clearly defined and understood. Nevertheless, their
      coexistence has synergistic effects on patient symptoms, response to therapy, and
      general outcomes. Taxonomically, asthma and OSA are syndromically defined
      entities that are quite heterogeneous, being characterized by a plethora of
      clinical phenotypes. The complex interactions between these conditions should
      take into account more specific etiopathogenic mechanisms or distinct disease
      endotypes. The potential clinical, pathogenic, and therapeutic significance of
      the disease endotypes is still emerging and needs further evaluation. We present
      here a review on the bidirectional relationships between asthma and OSA,
      including their clinical, pathophysiologic, and therapeutic connections.
      Furthermore, we propose here to look at these interactions beyond the development
      of comprehensive inventories of genotypes, clinical and pathophysiologic
      phenotypes, but in the larger context of obstructive lung and airway disorders,
      with the goal to reassess meaningful syndromes based on natural history and
      predictable patient outcomes, which will help us better stratify therapy in an
      era of personalized medicine. 

PMID- 24583903
TI  - The rationale/design of the Guimaraes/Vizela study: a multimodal population-based
      cohort study to determine global cardiovascular risk and disease.
AB  - BACKGROUND: Cardiovascular disease and dementia are growing medical and social
      problems in aging societies. Appropriate knowledge of cardiovascular disease and
      cognitive decline risk factors (RFs) are critical for global CVR health
      preventive intervention. Many epidemiological studies use case definition based
      on data collected/measured in a single visit, a fact that can overestimate
      prevalence rates and distant from clinical practice demanding criteria. Portugal
      displays an elevated stroke mortality rate. However, population's global CV risk
      characterization is limited, namely, considering traditional/nontraditional RF
      and new intermediate phenotypes of CV and renal disease. Association of
      hemodynamic variables (pulse wave velocity and central blood pressure) with
      global CVR stratification, cognitive performance, and kidney disease are
      practically inexistent at a dwelling population level. STUDY DESIGN AND METHODS:
      After reviewing published data, we designed a population-based cohort study to
      analyze the prevalence of these cardiovascular RFs and intermediate phenotypes,
      using random sampling of adult dwellers living in 2 adjacent cities. Strict
      definition of phenotypes was planned: subjects were observed twice, and several
      hemodynamic and other biological variables measured at least 3 months apart.
      RESULTS: Three thousand thirty-eight subjects were enrolled, and extensive data
      collection (including central and peripheral blood pressure, pulse wave
      velocity), sample processing, and biobank edification were carried out. One
      thousand forty-seven cognitive evaluations were performed. CONCLUSIONS: Seeking
      for CV risk reclassification, early identification of subjects at risk, and
      evidence of early vascular aging and cognitive and renal function decline, using
      the strict daily clinical practice criteria, will lead to better resource
      allocation in preventive measures at a population level.

PMID- 24583904
TI  - Improvement of sample size calculations for binary diagnostic test assessment.
AB  - OBJECTIVE: This study aimed to formulate a new R function to improve sample size
      calculation for more accurate estimations of sensitivity (Se) and specificity
      (Sp). METHODS: The developed function is based on the binDesign function of the
      binGroup R package. This allowed the use of an "exact" method based on the
      binomial distribution. In addition, the function takes into account a joint
      testing of Se and Sp and a nonmonotonous behavior of the power function. RESULTS:
      Four tables were generated to display the number of cases (or controls) in joint
      or separate assessments for an expected combination of Se (or Sp) and a
      determined difference between the expected Se (or Sp) and the minimum acceptable
      Se (or Sp). Using the formula for a joint testing of Se and Sp, it resulted in a
      higher increase of the sample sizes than simply allowing for the sawtooth shape
      of the power curve. CONCLUSION: Whenever equal Se and Sp values are important, a
      joint testing should be favored and used for sample size determination.

PMID- 24583905
TI  - Linking the developmental and degenerative theories of schizophrenia: association
      between infant development and adult cognitive decline.
AB  - Neurodevelopmental and neurodegenerative theories may be viewed as incompatible
      accounts that compete to explain the pathogenesis of schizophrenia. However, it
      is possible that neurodevelopmental and neurodegenerative processes could both
      reflect common underlying causal mechanisms. We hypothesized that cognitive
      dysfunction would gradually deteriorate over time in schizophrenia and the degree
      of this deterioration in adulthood would be predicted by an infant measure of
      neurodevelopment. We aimed to examine the association between age of learning to
      stand in infancy and deterioration of cognitive function in adulthood.
      Participants were nonpsychotic control subjects (n = 76) and participants with
      schizophrenia (n = 36) drawn from the Northern Finland 1966 Birth Cohort study.
      The schizophrenia group showed greater deterioration in abstraction with memory
      than controls, but there were no differences between schizophrenia and controls
      in rate of change of other cognitive measures. Age of learning to stand in
      infancy significantly inversely predicted later deterioration of abstraction with
      memory in adult schizophrenia (later infant development linked to greater
      subsequent cognitive deterioration during adulthood), possibly suggesting a link
      between abnormal neurodevelopmental and neurodegenerative processes in
      schizophrenia. 

PMID- 24583907
TI  - My Stages of Recovery.

PMID- 24583908
TI  - Evaluation of a compact mass spectrometer for routine support of pharmaceutical
      chemistry.
AB  - The suitability of a recently introduced inexpensive, compact mass spectrometer
      detector is evaluated for supporting pharmaceutical chemistry investigations.
      While high performance/high cost MS detectors dominate the marketplace, there is
      growing recognition of the need for a small, inexpensive MS detector with reduced
      capabilities for supporting synthetic chemistry investigations, where reduced
      sensitivity and unit mass resolution are often suitable for solving routine
      problems. In this study, the fundamental performance characteristics of the
      recently introduced Advion compact mass spectrometer were evaluated,
      investigating the use of the instrument for routine product and impurity
      identification, reaction monitoring, evaluation of potential genotoxic impurities
      and study of high molecular weight biomolecules. In general, the results of the
      evaluation show this compact and inexpensive mass spectrometer to be well suited
      for providing reliable support for pharmaceutical chemistry investigations, with
      sub-nanogram limit of detection and impurity identification below 0.1% being
      possible in some instance. 

PMID- 24583909
TI  - Rapid extraction and determination of amphetamines in human urine samples using
      dispersive liquid-liquid microextraction and solidification of floating organic
      drop followed by high performance liquid chromatography.
AB  - A novel, rapid, simple and sensitive dispersive liquid-liquid microextraction
      method based on the solidification of floating organic drop (DLLME-SFO) combined
      with high-performance liquid chromatography-ultraviolet detection (HPLC-UV) was
      used to determine amphetamine and methamphetamine in urine samples. The factors
      affecting the extraction efficiency of DLLME-SFO such as the kind and volume of
      the extraction and the disperser solvents, effect of concentration of K2CO3 and
      extraction time were investigated and the optimal extraction conditions were
      established. Under the optimum conditions (extraction solvent: 30.0MUl 1
      undecanol; disperser solvent: 300MUl acetonitrile; buffer concentration: 2% (w/v)
      K2CO3 and extraction time: 1min), calibration curves are linear in the range of
      10-3000MUgl(-1) and limit of detections (LODs) are in the range of 2-8MUgl(-1).
      The relative standard deviations (RSDs) for 100MUgl(-1) of amphetamine and
      methamphetamine in diluted urine are in the range of 6.2-7.8% (n=7). The method
      was successfully applied for the determination of amphetamine and methamphetamine
      in the actual urine samples. The relative recoveries of urine samples spiked with
      amphetamine and methamphetamine are 87.8-113.2%. The obtained results show that
      DLLME-SFO combined with HPLC-UV is a fast and simple method for the determination
      of amphetamine and methamphetamine in urine. 

PMID- 24583906
TI  - Alterations in brain activation during cognitive empathy are related to social
      functioning in schizophrenia.
AB  - Impaired cognitive empathy (ie, understanding the emotional experiences of
      others) is associated with poor social functioning in schizophrenia. However, it
      is unclear whether the neural activity underlying cognitive empathy relates to
      social functioning. This study examined the neural activation supporting
      cognitive empathy performance and whether empathy-related activation during
      correctly performed trials was associated with self-reported cognitive empathy
      and measures of social functioning. Thirty schizophrenia outpatients and 24
      controls completed a cognitive empathy paradigm during functional magnetic
      resonance imaging. Neural activity corresponding to correct judgments about the
      expected emotional expression in a social interaction was compared in
      schizophrenia subjects relative to control subjects. Participants also completed
      a self-report measure of empathy and 2 social functioning measures (social
      competence and social attainment). Schizophrenia subjects demonstrated
      significantly lower accuracy in task performance and were characterized by
      hypoactivation in empathy-related frontal, temporal, and parietal regions as well
      as hyperactivation in occipital regions compared with control subjects during
      accurate cognitive empathy trials. A cluster with peak activation in the
      supplementary motor area (SMA) extending to the anterior midcingulate cortex
      (aMCC) correlated with social competence and social attainment in schizophrenia
      subjects but not controls. These results suggest that neural correlates of
      cognitive empathy may be promising targets for interventions aiming to improve
      social functioning and that brain activation in the SMA/aMCC region could be used
      as a biomarker for monitoring treatment response. 

PMID- 24583910
TI  - Porphyromonas gingivalis-impaired innate immune response via NLRP3 proteolysis in
      endothelial cells.
AB  - Porphyromonas gingivalis (Pg) is involved in the link between periodontal
      diseases and atherosclerosis worsening. In periodontal cells, Pg modifies IL
      1beta expression via the NLRP3 inflammasome pathway activation. Our aim was to
      investigate NLRP3 inflammasome activation in endothelial cells (ECs) after Pg
      infection and Pg-LPS stimulation. In both situations, RT-PCR experiments
      demonstrated an increase of the NLRP3 mRNA level that can be potentiated by pre
      treatment of ECs with 5 mM ATP. However, Western blotting analysis revealed that
      Pg infection induced a proteolysis of NLRP3 protein and a major decrease of the
      native protein. After ATP pre-treatment and/or Pg-LPS stimulation, this
      proteolysis was not observed, while NLRP3 protein levels were increased.
      Proteolysis of the NLRP3 protein was not observed with heat-killed Pg and
      inhibition of ECs protein synthesis with cycloheximide did not abolish the NLRP3
      protein degradation induced by Pg infection in ATP pre-treated cells.
      Additionally, significant increases of secreted IL-1beta were measured after ATP
      pre-treatment and/or Pg-LPS stimulation, but not after Pg infection. These data
      showed that Pg and Pg-LPS differentially controlled the NLRP3 inflammasome
      pathway in ECs, and suggested a novel potential mechanism developed by Pg to
      reduce IL-1beta secretion and to escape host immune response.

PMID- 24583911
TI  - Eosinophilic inflammation of chronic rhinosinusitis with nasal polyps is related
      to OX40 ligand expression.
AB  - The aims of this study were to investigate OX40 ligand expression in sinus tissue
      from patients with nasal polyposis compared with patients with chronic
      rhinosinusitis without nasal polyps (NPs), and to determine if OX40 ligand
      expression is related to eosinophilic sinus infiltration. Twenty patients with
      chronic rhinosinusitis (11 with and nine without NPs) and seven controls were
      enrolled in the study. The mRNA expression of OX40 ligand and thymic stromal
      lymphopoietin and its receptor were analyzed. The immunoreactivity score for OX40
      ligand and the eosinophil count were obtained. The mRNA expression and
      immunoreactivity score of OX40 ligand were higher in patients with nasal
      polyposis than in patients without NPs, as well as healthy controls. The mRNA
      expression of thymic stromal lymphopoietin and its receptor was significantly
      higher in nasal polyposis than in the control, but not significantly higher than
      in chronic rhinosinusitis without NPs. A correlation between the number of OX40
      ligand-positive cells and the number of eosinophils in sinus biopsies was found
      only in patients with nasal polyposis. In conclusion, the thymic stromal
      lymphopoietin/OX40 ligand axis is up-regulated in nasal polyposis and is related
      to the intensity of eosinophilic inflammation. 

PMID- 24583912
TI  - Lipid releasing characteristics of microalgae species through continuous
      ultrasonication.
AB  - In this study, the lipid releasing characteristics of several microalgae species
      through continuous ultrasonication was examined. Two marine microalgae species,
      Tetraselmis suecica and Nannochloropsis sp., and one freshwater species,
      Chlorella sp. were ultrasonicated directly after cultivation. The cell disruption
      efficiency and lipids releasing pattern from microalgae cells were measured under
      various ultrasonication conditions. It was found that cell disruption efficiency
      correlates well with ultrasonication energy consumption despite the
      ultrasonication conditions. Lipids in Chlorella sp. that has rigid cell walls
      were released to the aqueous phase after cell disruption. T. suecica and
      Nannochloropsis sp. that have flexible cell membranes tend to coil up and retain
      the membrane lipids after disruption. Continuous ultrasonication can be a
      potential method to release the lipids in rigid walled microalgae species without
      expensive dewatering steps. 

PMID- 24583913
TI  - Starch and lipid accumulation in eight strains of six Chlorella species under
      comparatively high light intensity and aeration culture conditions.
AB  - The microalgae family Chlorella species are known to accumulate starch and
      lipids. Although nitrogen or phosphorous deficiencies promote starch and lipids
      formation in many microalgae, these deficiencies also limit their growth and
      productivity. Therefore, the Chlorellaceae strains were attempted to increase
      starch and lipids productivity under high-light-intensity conditions (600-MUmol
      photons m(-2)s(-1)). The 12:12-h light-dark (LD) cycle conditions elicited more
      stable growth than the continuous light (LL) conditions, whereas the starch and
      lipids yields increased in LL conditions. The amount of starch and lipids per
      cell increased in Chlorella viscosa and Chlorella vulgaris in sulfur-deficient
      medium, and long-chain fatty acids with 20 or more carbon atoms accumulated in
      cells grown in sulfur-deficient medium. Accumulation of starch and lipids was
      investigated in eight strains. The accumulation was strain-dependent, and varied
      according to the medium and light conditions. Five of the eight Chlorella strains
      exhibited similar accumulation patterns.

PMID- 24583914
TI  - Wet air oxidation pretreatment of biomethanated distillery effluent: mapping
      pretreatment efficiency in terms color, toxicity reduction and biogas generation.
AB  - The effluents from molasses-based distilleries after biomethanation are beset
      with problems of intensified dark brown color, high residual COD, low
      biodegradability index (BOD/COD ratio <0.2) and toxicity issues for possible land
      application as a potential fertilizer. Wet air oxidation (WAO) pretreatment of
      biomethanated distillery effluent resulted in substantial enhancement in the
      biodegradability index (BI) (up to 0.8). WAO pretreated effluent on anaerobic
      digestion indicated favorable biogas generation with methane content up to 64%
      along with concomitant COD reduction up to 54.75%. The HPLC analysis indicated
      that the pretreatment facilitated degradation of major color containing compounds
      namely melanoidins, up to 97.8%. The pretreated effluent with enhanced
      biodegradability along with substantially reduced color also indicated positive
      effect on seed germination (up to 100%), implying toxicity reduction of the
      effluent post WAO pretreatment. 

PMID- 24583915
TI  - Intracellular calcium and the mechanism of the dip in the anodal strength
      interval curve in cardiac tissue.
AB  - BACKGROUND: The strength-interval (SI) curve is an important measure of
      refractoriness in cardiac tissue. The anodal SI curve contains a "dip" in which
      the S2 threshold increases with interval. Two explanations exist for this dip:
      (1) electrotonic interaction between regions of depolarization and
      hyperpolarization; and (2) the sodium-calcium exchange (NCX) current. The goal of
      this study is to use mathematical modeling to determine which explanation is
      correct. METHODS AND RESULTS: The bidomain model represents cardiac tissue and
      the Luo-Rudy model describes the active membrane. The SI curve is determined by
      applying a threshold stimulus at different time intervals after a previous action
      potential. During space-clamped and equal-anisotropy-ratios simulations, anodal
      excitation does not occur. During unequal-anisotropy-ratios simulations,
      electrotonic currents, not membrane currents, are present during the few
      milliseconds before excitation. The dip disappears with no NCX current, but is
      present with 50% or 75% reduction of it. The calcium-induced-calcium-release
      (CICR) current has little effect on the dip. CONCLUSIONS: These results indicate
      that neither the NCX nor the CICR current is responsible for the dip in the
      anodal SI curve. It is caused by the electrotonic interaction between regions of
      depolarization and hyperpolarization following the S2 stimulus.

PMID- 24583916
TI  - Acute myocardial infarction and cardiogenic shock caused by a huge right Valsalva
      sinus aneurysm.

PMID- 24583917
TI  - Alcohol and atrial fibrillation.

PMID- 24583918
TI  - Increased serum level of soluble vascular endothelial growth factor receptor-1 is
      associated with poor coronary collateralization in patients with stable coronary
      artery disease.
AB  - BACKGROUND: The present study investigated whether serum levels of soluble
      vascular endothelial growth factor receptor (sVEGFR)-1, -2 and -3 are related to
      poor coronary collateralization in patients with stable coronary artery disease
      (CAD). METHODS AND RESULTS: Serum levels of sVEGFR-1, -2, -3, VEGF, and placental
      growth factor (PLGF) were determined in 403 consecutive patients with
      angiographic total or subtotal occlusion of at least 1 major coronary artery. The
      degree of collateralization was graded according to the Rentrop scoring system.
      Low (Rentrop score of 0 or 1) and high (Rentrop score of 2 or 3) coronary
      collateralization occurred in 161 and 242 patients, respectively. Serum levels of
      sVEGFR-1 and -2 were significantly elevated, in contrast, VEGF and PLGF levels
      were remarkably decreased in patients with low collateralization than in those
      with high collateralization (all P<0.05). Significant differences in sVEGFR-1,
      VEGF and PLGF levels was consistently detected between the low and high
      collateralization subgroups for patients with and without type 2 diabetes
      mellitus (DM) (for all comparisons, P<0.01). Multivariable regression analysis
      revealed that DM, dyslipidemia, elevated sVEGFR-1, and reduced VEGF and PLGF in
      serum were independently associated with a low degree of coronary
      collateralization. CONCLUSIONS: Increased serum sVEGFR-1 level is associated with
      poor coronary collateralization in patients with stable CAD. Type 2 DM is a
      predominant factor affecting collateral growth in these patients.

PMID- 24583919
TI  - Tobacco smoking decreases plasma concentration of the emerging cardiovascular
      risk marker, L-homoarginine.
AB  - BACKGROUND: Tobacco smoking is one of the most important risk factors for
      cardiovascular disease (CVD) and few biomarkers have been linked to the increased
      risk of CVD and tobacco smoking. Tobacco smoke has been shown to elevate the
      plasma levels of asymmetric dimethylarginine (ADMA), a metabolite of L-arginine
      and an endogenous inhibitor of endothelial nitric oxide synthase. The other
      potential biomarker that has not been studied to date is L-homoarginine, a
      homolog of L-arginine. The aim of this study was to evaluate the effects of
      cigarette smoking on L-homoarginine and other CVD biomarkers. METHODS AND
      RESULTS: In a cross-sectional study of 231 healthy male volunteers, we measured
      plasma levels of L-homoarginine, L-arginine, and ADMA using the HPLC method. In
      smokers, we found that plasma L-homoarginine levels were 16.7% lower compared
      with nonsmokers after adjusting for age, body mass index, plasma creatinine, and
      metal blood levels (P<0.05). Plasma ADMA levels were only 6.0% higher in smokers
      when compared with the levels found in nonsmokers (P>0.05). CONCLUSIONS: Our
      results suggest that, in contrast to ADMA, there is a strong association between
      exposure to tobacco smoke and plasma L-homoarginine levels. Further research in
      this field is needed to explain the mechanisms of the relationship of low L
      homoarginine levels, smoking, and cardiovascular health.

PMID- 24583920
TI  - Impaired mechanics and matrix metalloproteinases/inhibitors expression in female
      ascending thoracic aortic aneurysms.
AB  - We hypothesized that female gender may have a specific negative impact on the
      mechanical characteristics, composition, and expression of matrix
      metalloproteinases/tissue inhibitors (MMPs/TIMPs) in the wall of ascending
      thoracic aortic aneurysms (ATAAs). Degenerative ATAAs were resected from 35
      patients (age: 67+/-2 years, male: 20, ATAA diameter: 5.5+/-0.1cm) undergoing
      elective surgery. Tissue specimens were grouped by gender, region, and direction
      and submitted to immunohistochemistry for semi-quantitative assessment of MMP-2,
      MMP-9, TIMP-1, and TIMP-2 expressions, i.e. of staining intensity in
      extracellular matrix and immunoreactivity in vascular cells, as well as to
      histology for quantitation of elastin/collagen contents. Biomechanical
      characterization by the Fung-type model and examination of failure properties was
      performed. Gender differences in patient age, ATAA diameter, and ATAA
      diameter/body-surface area were non-significant. Increased MMP-2 and MMP-9, and
      decreased TIMP-1 and TIMP-2 expressions were observed in females.
      Elastin/collagen contents were higher in males than females, as was failure
      stress in circumferential but not longitudinal specimens. In both directions,
      failure stretch was invariant, while the Fung-type model parameters and elastic
      moduli calculated at physiologic stress levels were higher in females, suggestive
      of increased wall stiffness compared to males. MMP and TIMP expressions did not
      differ with region, unlike failure stress longitudinally that was greater
      posteriorly than anteriorly. The female gender is associated with impaired ATAA
      strength and increased stiffness, relating to the more extensive extracellular
      matrix breakdown and significantly higher ratio of MMP/TIMP expression witnessed
      in females. The present data may aid to identify the underlying pathophysiology
      accountable for the higher rupture risk, documented by epidemiologic studies in
      females. 

PMID- 24583921
TI  - Biomechanical characteristics of the porcine denticulate ligament in different
      vertebral levels of the cervical spine-preliminary results of an experimental
      study.
AB  - BACKGROUND: Few studies exist on the mechanical properties of denticulate
      ligaments and none report the variation in these properties at different levels
      of the spine. The aim of this study was to perform an experimental determination
      of load-extension and stress-strain characteristics of the denticulate ligament
      and to establish if their properties change at different vertebral levels of the
      cervical spine. METHOD: The study was carried out on a total of 98 porcine
      denticulate ligament samples dissected from seven fresh porcine cervical spinal
      cord specimens. All of the samples were subjected to an uniaxial tensile test at
      a speed of 2mm/min, during which the load-extension characteristics were
      registered. RESULTS: The analysis revealed a decrease of the failure force in the
      caudal orientation indicated by significant differences between the C1 (1.04+/
      0.41N) and C7 (0.55+/-0.12N) vertebral levels (P=0.037). The average ultimate
      force that broke the denticulate ligaments was 0.88N. The mean value of Young's
      modulus was 2.06MPa with a minimum of 1.31MPa for C7 and maximum of 2.46MPa for
      C5. CONCLUSIONS: The values of the denticulate ligament failure force in samples
      from different cervical vertebrae levels differ significantly. The presented data
      should be taken into consideration during numerical modelling of the human
      cervical spinal cord.

PMID- 24583922
TI  - Gestural development and its relation to a child's early vocabulary.
AB  - Gesture and language are tightly connected during the development of a child's
      communication skills. Gestures mostly precede and define the way of language
      development; even opposite direction has been found. Few recent studies have
      focused on the relationship between specific gestures and specific word
      categories, emphasising that the onset of one gesture type predicts the onset of
      certain word categories or of the earliest word combinations. The aim of this
      study was to analyse predicative roles of different gesture types on the onset of
      first word categories in a child's early expressive vocabulary. Our data show
      that different types of gestures predict different types of word production.
      Object gestures predict open-class words from the age of 13 months, and gestural
      routines predict closed-class words and social terms from 8 months. Receptive
      vocabulary has a strong mediating role for all linguistically defined categories
      (open- and closed-class words) but not for social terms, which are the largest
      word category in a child's early expressive vocabulary. Accordingly, main
      contribution of this study is to define the impact of different gesture types on
      early expressive vocabulary and to determine the role of receptive vocabulary in
      gesture-expressive vocabulary relation in the Croatian language.

PMID- 24583923
TI  - The secret origins and surprising fates of pancreas tumors.
AB  - Pancreatic ductal adenocarcinoma (PDA) is especially deadly due to its
      recalcitrance to current therapies. One of the unique qualities of PDA that may
      contribute to this resistance is a striking plasticity of differentiation states
      starting at tumor formation and continuing throughout tumor progression,
      including metastasis. Here, we explore the earliest steps of tumor formation and
      neoplastic progression and how this results in a fascinating cellular
      heterogeneity that is probably critical for tumor survival and progression. We
      hypothesize that reinforcing differentiation pathways run awry or targeting
      morphologically and molecularly distinct tumor stem-like cells may hold promise
      for future treatments of this deadly disease.

PMID- 24583924
TI  - High prevalence of mTOR complex activity can be targeted using Torin2 in
      papillary thyroid carcinoma.
AB  - The mammalian target of rapamycin (mTOR) signaling cascade is a key regulatory
      pathway controlling initiation of messenger RNA in mammalian cells. Although
      dysregulation of mTOR signaling has been reported earlier in cancers, there is
      paucity of data about mTOR expression in papillary thyroid carcinoma (PTC).
      Therefore, in this study, we investigated the presence of mTORC2 and mTORC1
      complexes in a large cohort of >500 PTC samples. Our clinical data showed the
      presence of active mTORC1 and mTORC2 in 81 and 39% of PTC samples, respectively.
      Interestingly, coexpression of mTORC1 and mTORC2 activity was seen in a 32.5%
      (164/504) of the PTC studied and this association was statistically significant
      (P = 0.0244). mTOR signaling complex was also found to be associated with
      activated AKT and 4E-BP1. In vitro, using Torin2, a second-generation mTOR
      inhibitor or gene silencing of mTOR expression prevented mTORC1 and mTORC2
      activity leading to inactivation of P70S6, 4E-BP1, AKT and Bad. Inhibition of
      mTOR activity led to downregulation of cyclin D1, a gene regulated by messenger
      RNA translation via phosphorylation of 4E-BP1. Torin2 treatment also inhibited
      cell viability and induced caspase-dependent apoptosis via activation of
      mitochondrial apoptotic pathway in PTC cells. Finally, Torin2 treatment induces
      anticancer effect on PTC xenograft tumor growth in nude mice via inhibition of
      mTORC1 and mTORC2 and its associated pathways. Our results suggest that
      coexpression of mTORC1 and mTORC2 is seen frequently in the clinical PTC samples
      and dual targeting of mTORC1 and mTORC2 activity may be an attractive therapeutic
      target for treatment of PTC.

PMID- 24583925
TI  - TR4 nuclear receptor functions as a tumor suppressor for prostate tumorigenesis
      via modulation of DNA damage/repair system.
AB  - Testicular nuclear receptor 4 (TR4), a member of the nuclear receptor
      superfamily, plays important roles in metabolism, fertility and aging. The
      linkage of TR4 functions in cancer progression, however, remains unclear. Using
      three different mouse models, we found TR4 could prevent or delay prostate cancer
      (PCa)/prostatic intraepithelial neoplasia development. Knocking down TR4 in human
      RWPE1 and mouse mPrE normal prostate cells promoted tumorigenesis under
      carcinogen challenge, suggesting TR4 may play a suppressor role in PCa
      initiation. Mechanism dissection in both in vitro cell lines and in vivo mice
      studies found that knocking down TR4 led to increased DNA damage with altered DNA
      repair system that involved the modulation of ATM expression at the
      transcriptional level, and addition of ATM partially interrupted the TR4 small
      interfering RNA-induced tumorigenesis in cell transformation assays.
      Immunohistochemical staining in human PCa tissue microarrays revealed ATM
      expression is highly correlated with TR4 expression. Together, these results
      suggest TR4 may function as a tumor suppressor to prevent or delay prostate
      tumorigenesis via regulating ATM expression at the transcriptional level.

PMID- 24583928
TI  - Unstacked double-layer templated graphene for high-rate lithium-sulphur
      batteries.
AB  - Preventing the stacking of graphene is essential to exploiting its full potential
      in energy-storage applications. The introduction of spacers into graphene layers
      always results in a change in the intrinsic properties of graphene and/or induces
      complexity at the interfaces. Here we show the synthesis of an intrinsically
      unstacked double-layer templated graphene via template-directed chemical vapour
      deposition. The as-obtained graphene is composed of two unstacked graphene layers
      separated by a large amount of mesosized protuberances and can be used for high
      power lithium-sulphur batteries with excellent high-rate performance. Even after
      1,000 cycles, high reversible capacities of ca. 530 mA h g(-1) and 380 mA h g(-1)
      are retained at 5 C and 10 C, respectively. This type of double-layer graphene is
      expected to be an important platform that will enable the investigation of
      stabilized three-dimensional topological porous systems and demonstrate the
      potential of unstacked graphene materials for advanced energy storage,
      environmental protection, nanocomposite and healthcare applications.

PMID- 24583926
TI  - HOTAIR long non-coding RNA is a negative prognostic factor not only in primary
      tumors, but also in the blood of colorectal cancer patients.
AB  - Colorectal cancer (CRC) is one of the main causes of death of neoplasia. Demand
      for predictive and prognostic markers to reverse this trend is increasing. Long
      non-coding RNA HOTAIR (Homeobox Transcript Antisense Intergenic RNA)
      overexpression in tumors was previously associated with poor prognosis and higher
      mortality in different carcinomas. We analyzed HOTAIR expression levels in tumor
      and blood of incident sporadic CRC patients in relation to their overall survival
      with the aim to evaluate surrogate prognostic marker for CRC. Tissue donor group
      consisted of 73 CRC patients sampled for tumor and normal tissue. Blood donor
      group was represented by 84 CRC patients compared with 40 healthy controls.
      Patients were characterized for tumor-node-metastasis stage, tumor grade,
      microsatellite instability and tumor penetration by stromal cells. HOTAIR levels
      were assessed by real-time quantitative PCR. CRC patients had higher HOTAIR
      expression in blood than healthy controls (P = 0.0001), whereas there was no
      difference in HOTAIR levels between tumor and adjacent mucosa of CRC patients.
      HOTAIR levels positively correlated between blood and tumor (R = 0.43, P = 0.03).
      High HOTAIR levels in tumors were associated with higher mortality of patients
      [Cox's proportional hazard, hazard ratio = 4.4, 95% confidence interval: 1.0
      19.2, P = 0.046]. The hazard ratio was even higher when blood HOTAIR levels were
      taken into account (hazard ratio = 5.9, 95% confidence interval: 1.3-26.1, P =
      0.019). Upregulated HOTAIR relative expression in primary tumors and in blood of
      CRC patients is associated with unfavorable prognosis. Our data suggest that
      HOTAIR blood levels may serve as potential surrogate prognostic marker in
      sporadic CRC.

PMID- 24583929
TI  - DNA repair: Chromatin remodeling without H2A.Z?

PMID- 24583931
TI  - Efficacy of entecavir in chronic hepatitis B patients with persistently normal
      alanine aminotransferase: randomized, double-blind, placebo-controlled study.
AB  - BACKGROUND: It is still inconclusive whether chronic hepatitis B (CHB) patients
      with persistently normal alanine aminotransferase (PNALT) should receive
      nucleoside/nucleotide analogues. This study is to evaluate the efficacy of
      entecavir in improving liver histology in CHB patients with PNALT. METHODS: In
      this prospective randomized, double-blind, placebo-controlled study, 380 CHB
      patients with PNALT were screened, 82 patients received biopsy and 43 patients
      met the HBV DNA and histology criteria and were randomly assigned to either an
      entecavir or placebo group for 52 weeks, with 22 and 21 in each group,
      respectively. The primary objective was to evaluate histological improvement. The
      secondary objective is to evaluate virological efficacy. RESULTS: A total of
      eight (38.1%) patients in the entecavir group and eight (44.4%) in the placebo
      group (P=0.752) showed histological improvement. The decrease in total Knodell
      scores (+/-sd) was 1.3 +/-1.9 in the entecavir group and 1.5 +/-2.2 in the
      placebo group (P=0.803). The subjects with undetectable HBV DNA at week 52 were
      16/21 (76.2%) in the entecavir group and 0/18 (0%) in the placebo group
      (P<0.001). The mean HBV DNA reduction from baseline to week 52 was 4.73 +/-0.83
      in the entecavir and 0.25 +/-0.81 in the placebo group (P<0.001). CONCLUSIONS:
      CHB patients with PNALT receiving entecavir therapy for one year achieved
      virological efficacy, but not histological benefit. ClinicalTrials.gov number
      NCT01833611.

PMID- 24583930
TI  - Effects of the fatty acid amide hydrolase inhibitor URB597 on pain-stimulated and
      pain-depressed behavior in rats.
AB  - Cannabinoid receptor (CBR) agonists produce antinociception in conventional
      preclinical assays of pain-stimulated behavior but are not effective in
      preclinical assays of pain-depressed behavior. Fatty acid amide hydrolase (FAAH)
      inhibitors increase physiological levels of the endocannabinoid anandamide, which
      may confer improved efficacy and safety relative to direct CBR agonists. To
      further evaluate FAAH inhibitors as candidate analgesics, this study assessed the
      effects of the FAAH inhibitor URB597 in assays of acute pain-stimulated and pain
      depressed behavior in male Sprague-Dawley rats. Intraperitoneal injection of
      dilute lactic acid served as a noxious stimulus to stimulate a stretching
      response or depress positively reinforced operant behavior (intracranial self
      stimulation), and URB597 was tested 1 and 4 h after administration. Consistent
      with FAAH inhibitor effects in other assays of pain-stimulated behavior, URB597
      (1-10 mg/kg intraperitoneally) produced dose-related and CB1R-mediated decreases
      in acid-stimulated stretching. Conversely, in the assay of acid-depressed
      intracranial self-stimulation, URB597 produced a delayed, partial and non-CBR
      mediated antinociceptive effect. The antinociceptive dose of URB597 (10 mg/kg)
      increased plasma and brain anandamide levels. These results suggest that URB597
      produces antinociception in these models of 'pain stimulated' and 'pain
      depressed' behavior, but with different rates of onset and differential
      involvement of CBRs. 

PMID- 24583932
TI  - Use of the BIPM calorimetric and ionometric standards in megavoltage photon beams
      to determine Wair and Ic.
AB  - The BIPM graphite calorimeter standard for absorbed dose to water has been used
      in conjunction with an ionization chamber of known volume and with Monte Carlo
      simulations of these arrangements to determine the value for Wair in (60)Co
      radiation and in accelerator photon beams up to 25 MV. The results show no
      evidence for a variation in Wair at the 0.2% level over this energy range. Taking
      the constancy of Wair as established, the best estimate is Wair = 34.03 eV with a
      standard uncertainty of 0.21%. Consistent with this analysis, and assuming the
      use of the grain density in evaluating the stopping power of graphite, is the
      value Ic = 81.1 eV for the mean excitation energy for graphite, with standard
      uncertainty 1.8 eV.

PMID- 24583935
TI  - I never stop..learning.

PMID- 24583936
TI  - Learning: a lifelong journey.

PMID- 24583934
TI  - Lucifensins, the Insect Defensins of Biomedical Importance: The Story behind
      Maggot Therapy.
AB  - Defensins are the most widespread antimicrobial peptides characterised in
      insects. These cyclic peptides, 4-6 kDa in size, are folded into alpha
      helical/beta-sheet mixed structures and have a common conserved motif of three
      intramolecular disulfide bridges with a Cys1-Cys4, Cys2-Cys5 and Cys3-Cys6
      connectivity. They have the ability to kill especially Gram-positive bacteria and
      some fungi, but Gram-negative bacteria are more resistant against them. Among
      them are the medicinally important compounds lucifensin and lucifensin II, which
      have recently been identified in the medicinal larvae of the blowflies Lucilia
      sericata and Lucilia cuprina, respectively. These defensins contribute to wound
      healing during a procedure known as maggot debridement therapy (MDT) which is
      routinely used at hospitals worldwide. Here we discuss the decades-long story of
      the effort to isolate and characterise these two defensins from the bodies of
      medicinal larvae or from their secretions/excretions. Furthermore, our previous
      studies showed that the free-range larvae of L. sericata acutely eliminated most
      of the Gram-positive strains of bacteria and some Gram-negative strains in
      patients with infected diabetic foot ulcers, but MDT was ineffective during the
      healing of wounds infected with Pseudomonas sp. and Acinetobacter sp. The
      bactericidal role of lucifensins secreted into the infected wound by larvae
      during MDT and its ability to enhance host immunity by functioning as
      immunomodulator is also discussed. 

PMID- 24583933
TI  - Avian antimicrobial host defense peptides: from biology to therapeutic
      applications.
AB  - Host defense peptides (HDPs) are an important first line of defense with
      antimicrobial and immunomoduatory properties. Because they act on the microbial
      membranes or host immune cells, HDPs pose a low risk of triggering microbial
      resistance and therefore, are being actively investigated as a novel class of
      antimicrobials and vaccine adjuvants. Cathelicidins and beta-defensins are two
      major families of HDPs in avian species. More than a dozen HDPs exist in birds,
      with the genes in each HDP family clustered in a single chromosomal segment,
      apparently as a result of gene duplication and diversification. In contrast to
      their mammalian counterparts that adopt various spatial conformations, mature
      avian cathelicidins are mostly alpha-helical. Avian beta-defensins, on the other
      hand, adopt triple-stranded beta-sheet structures similar to their mammalian
      relatives. Besides classical beta-defensins, a group of avian-specific beta
      defensin-related peptides, namely ovodefensins, exist with a different six
      cysteine motif. Like their mammalian counterparts, avian cathelicidins and
      defensins are derived from either myeloid or epithelial origin expressed in a
      majority of tissues with broad-spectrum antibacterial and immune regulatory
      activities. Structure-function relationship studies with several avian HDPs have
      led to identification of the peptide analogs with potential for use as
      antimicrobials and vaccine adjuvants. Dietary modulation of endogenous HDP
      synthesis has also emerged as a promising alternative approach to disease control
      and prevention in chickens. 

PMID- 24583937
TI  - Understanding vasoactive medications: focus on pharmacology and effective
      titration.
AB  - In the care of the critically ill patient, the use of vasoactive substances such
      as vasopressors and inotropes can be a potentially lifesaving intervention. An
      understanding of the pathophysiology of the various types of shock and
      pharmacology of the pharmacological agents used in the treatment of shock is
      necessary for intensive care unit clinicians to make appropriate decisions
      regarding when vasopressors or inotropes are indicated and assess their
      effectiveness. This review article will provide background on the different types
      of shock, compare and contrast the commonly used vasoactive substances in
      critically ill patients, discuss titration strategies for these agents, and
      review management of extravasation of these agents. 

PMID- 24583938
TI  - Management of surgical patients with bleeding disorders.
AB  - Invasive procedures for patients with bleeding disorders require planning on the
      part of the health care team. The patient population affected involves those with
      hereditary bleeding disorders, such as von Willebrand disease or hemophilia; in
      addition, patients who use antithrombotic drugs must be considered and their care
      managed. The choice of treatment depends on a number of factors, including the
      procedure planned, the type and severity of the disorder, and the age and
      morbidity of the patient. The indications, dosing, and timing of presurgical and
      surgical interventions will be reviewed, as well as special considerations for
      vascular access devices. 

PMID- 24583939
TI  - A time and motion study of peripheral venous catheter flushing practice using
      manually prepared and prefilled flush syringes.
AB  - Peripheral venous catheters (PVCs) are the simplest and most frequently used
      method for drug, fluid, and blood product administration in the hospital setting.
      It is estimated that up to 90% of patients in acute care hospitals require a PVC;
      however, PVCs are associated with inherent complications, which can be mechanical
      or infectious. There have been a range of strategies to prevent or reduce PVC
      related complications that include optimizing patency through the use of
      flushing. Little is known about the current status of flushing practice. This
      observational study quantified preparation and administration time and identified
      adherence to principles of Aseptic Non-Touch Technique and organizational
      protocol on PVC flushing by using both manually prepared and prefilled syringes. 

PMID- 24583940
TI  - Catheter-associated thrombosis in children: single-institution experience and
      review of pediatric venous thromboembolic disease.
AB  - Central venous catheters and peripherally inserted central catheters are widely
      used in children with serious chronic diseases. In this report, data about
      catheters and venous thromboembolic disease (VTE) in children will be reviewed,
      and the experience of a single academic children's hospital will be described.
      Two separate data sets that examine overlapping subpopulations will be reported:
      (1) the proportion of pediatric patients with catheters who develop VTE and (2)
      the proportion of patients referred to pediatric hematology for VTE who have
      catheters. The limitations of current pilot data and the authors' approach to
      better define this problem and its prevention are discussed. 

PMID- 24583941
TI  - Emerging therapies for autoimmune disorders.
AB  - Several monoclonal antibodies and other biologic drugs are used to treat a
      variety of common autoimmune disorders that are progressive in nature or
      resistant to standard therapies. Although monoclonal antibodies were recently
      removed from the hazardous drugs list, most of these drugs are considered high
      risk substances that require specialized knowledge regarding care before, during,
      and after administration. Yet no national standards exist for nurses working with
      autoimmune patients, nor have minimum nursing practice competency guidelines been
      identified. Expert practitioners must continue to educate other health care
      professionals about the drugs, their intended and off-label uses, their potential
      side effects, and proactive measures that need to be taken to ensure patient
      safety during the entire drug administration process. 

PMID- 24583942
TI  - Recommendations for improving safety practices with short peripheral catheters.

PMID- 24583944
TI  - Discrepancy between chronological age and felt age: age group difference in
      objective and subjective health as correlates.
AB  - OBJECTIVE: Guided by the social comparison theory, we examined correlates of the
      discrepancy between chronological and felt ages in three age groups of community
      dwelling older adults: 65 to 69, 70 to 79, and 80 and older. METHOD: Data from
      the National Health and Aging Trends Study and linear regression models were used
      to test the hypothesis that age discrepancy would be significantly associated
      with objective health indicators among those in the 65 to 69 and 70 to 79 age
      groups but not among the 80+ group. RESULTS: Objective health indicators were
      significantly associated with age discrepancy only in the 70 to 79 age group,
      while subjective health perceptions and psychological well-being were
      significantly associated with age discrepancy in all age groups. DISCUSSION: The
      correlates of the discrepancy in the 65 to 69 age group appear to resemble those
      in the 80+ group more than those in the 70 to 79 age group. Further research is
      needed to identify the determinants of age group differences.

PMID- 24583945
TI  - Short period of oxygenation releases latch on peat decomposition.
AB  - Extreme summer droughts are expected to occur more often in the future in NW
      Europe due to climate change. These droughts might accelerate the rate of peat
      oxidation in drained peat areas, with impacts on soil subsidence, GHG emission
      and water quality. This study aimed at providing more insight in the oxidation of
      deep peat layers that had not previously been exposed to air, the so-called
      secondary decomposition. We incubated two types of peat (eutrophic and
      oligotrophic), sampled from permanently anoxic peat layers from nature reserves
      and agricultural peat meadows. Peat samples were incubated for thirteen weeks
      under anoxic conditions, but were exposed to air for one to eight weeks. The
      production of CO2 and CH4 was quantified as a proxy for decomposition;
      concentrations of soluble nutrients and phenolic compounds were also measured.
      The results showed that oxygenation led to a steep increase in the rate of
      decomposition, indicated by higher carbon loss rates during and after oxygenation
      compared to non-oxygenated samples. Carbon loss rates increased more for
      eutrophic peat (agricultural area: 352%, nature reserve: 182%) than for
      oligotrophic peat (83% and 159% respectively). Most peat samples investigated
      showed higher post-oxygenation CO2 and/or CH4 production compared to the anoxic
      pre-oxygenation period. This indicates that oxygenation stimulates decomposition,
      even after anoxic conditions have returned. Contrary to the enzymic latch theory,
      no effects of oxygenation on the concentrations of soluble or condensed phenolic
      compounds were detected. Soluble nutrient concentrations did not change due to
      oxygenation either. Noteworthy is the occurrence of pyrite mineralization and
      associated acidification in eutrophic peat. Thus, low summer water levels, for
      example due to climate change, should be avoided in order to limit exceptionally
      high decomposition rates and associated problems such as increasing subsidence
      rates, greenhouse gas emission, sulfate release and acidification. 

PMID- 24583946
TI  - Fate of antimicrobials and antimicrobial resistance genes in simulated swine
      manure storage.
AB  - The behavior of three antibiotics (bacitracin, chlortetracycline, and tylosin)
      and two classes of antibiotic resistance genes (ARGs), tet and erm, were
      monitored in swine manure slurry under anaerobic conditions. First-order decay
      rates were determined for each antibiotic with half-lives ranging from 1 day
      (chlortetracycline) to 10 days (tylosin). ARGs were monitored in the swine manure
      slurry, and losses of approximately 1 to 3 orders of magnitude in relative
      abundance were observed during the 40 day storage period. First-order degradation
      profiles were observed for chlortetracycline and its corresponding resistance
      genes, tet(X) and tet(Q). Tylosin was degraded to approximately 10% of the
      starting concentration by day 40; however, the relative abundance of erm(B)
      remained at 50-60% of the initial relative abundance while the relative abundance
      of erm(F) decreased by 80-90%, consistent with tylosin. These results indicate
      that tet resistance genes respond primarily to chlortetracycline antimicrobials,
      and may be lost when the parent tetracycline compound is degraded. In contrast,
      erm(B) resistance gene may respond to a range of antimicrobials in animal manure,
      and may persist despite losses of tylosin.

PMID- 24583947
TI  - Skin involvement in lymphomas caused by Marek's disease virus infection in Silkie
      chickens.
AB  - The Silkie is a typical Chinese breed of chicken. In 2012, batches of Silkies
      were found to have diffuse tumor-like nodules on their skin after feather
      removal, when they were slaughtered at about 60 days old. Gross examination
      showed no visible neoplastic lesions on the visceral organs and peripheral
      nerves, except slight splenomegaly in individual chickens. The disease was
      prevalent, with high condemnation rates for skin lesions, which caused great
      economic losses to the company. Tissues, including skin, visceral organs, and
      peripheral nerves, were collected for histologic examination. Heparinized blood
      samples were collected for virus isolation and identification. Marek's disease
      virus (MDV), Reticuloendotheliosis virus (REV), and Avian leukosis virus (ALV)
      were analyzed, using polymerase chain reaction (PCR) tests. Histologic
      examination showed that all of the tumor-like nodules on the skin were lymphomas.
      Lymphoproliferative lesions occurred mostly on the skin and only a few on the
      viscera, including the liver and proventriculus. Infected chick embryo
      fibroblasts showed clear cytopathic effects; indirect fluorescent antibody test
      for envelope glycoprotein B was positive. In addition, PCR indicated the presence
      of MDV serotype 1 infection without REV and ALV. A phylogenetic tree of the Meq
      gene showed that the isolate (SD121201) and Chinese reference strains, which are
      very virulent MDVs, are in the same clade. It was concluded that the Silkies
      tested were infected with MDV serotype 1. The Marek's disease epidemic has been
      controlled using CVI988/Rispens vaccines. 

PMID- 24583948
TI  - Evaluation of a disintegrin-like and metalloprotease with thrombospondin type 1
      repeat motifs 13 (ADAMTS13) activity enzyme-linked immunosorbent assay for
      measuring plasma ADAMTS13 activity in dogs.
AB  - A disintegrin-like and metalloprotease with thrombospondin type 1 repeat motifs
      13 (ADAMTS13) is a von Willebrand factor (vWF)-cleaving protease. Deficiencies in
      ADAMTS13 activity are known to cause thrombotic diseases in human beings. The
      present study evaluated whether the human ADAMTS13 activity enzyme-linked
      immunosorbent assay (ELISA) kit containing human vWF73 (a minimal substrate) and
      anti-N10 antibody (which specifically recognizes the decapeptide of the C
      terminal edge of cleaved vWF by human ADAMTS13) is applicable to the measurement
      of canine plasma ADAMTS13 activity. Human vWF73 fused with a GST-tag and a His
      tag (GST-hvWF73-His) was reacted with recombinant canine (rc)ADAMTS13, canine
      plasma, and human plasma, and then used in Western blotting using anti-N10
      antibody. Linearity and intra- and interassay reproducibility of the human
      ADAMTS13 activity ELISA kit in canine plasma were further evaluated. Finally,
      plasma ADAMTS13 activity was measured in 13 healthy dogs and 6 dogs with
      bacteremia using the human ADAMTS13 activity ELISA kit. Cleaved products with a
      28-kDa GST-hvWF73-His were detected specifically in rcADAMTS13 as well as in
      human ADAMTS13, and also in canine plasma by anti-N10 antibody, showing excellent
      linearity. Intra-assay coefficient of variation (CV) was 3.0-12.4%, and
      interassay CV was 11.5-12.5%. The ADAMTS13 activity was significantly lower in
      dogs with bacteremia than in healthy dogs (P = 0.0025). The current study
      revealed that the human ADAMTS13 activity ELISA kit is applicable for measurement
      of canine plasma ADAMTS13 activity to elucidate the pathology of thrombotic
      diseases in dogs. 

PMID- 24583949
TI  - Hypoxia in Leishmania major skin lesions impairs the NO-dependent leishmanicidal
      activity of macrophages.
AB  - Cure of infections with Leishmania major is critically dependent on the ability
      of macrophages to induce the type 2 nitic oxide (NO) synthase (NOS2) that
      produces high levels of NO in the presence of ample oxygen. Therefore, we
      analyzed the oxygen levels found in leishmanial skin lesions and their effect on
      the NOS2-dependent leishmanicidal activity of macrophages (MPhi). When L. major
      skin lesions of self-healing C57BL/6 mice reached their maximum size, the
      infected tissue displayed low oxygen levels (pO2~21 Torr). MPhi activated under
      these oxygen tensions failed to produce sufficient amounts of NO to clear L.
      major. Nos2-deficient and hypoxic wild-type macrophages displayed a similar
      phenotype. Killing was restored when MPhi were reoxygenated or exposed to a NO
      donor. The resolution of the lesion in C57BL/6 mice was paralleled by an increase
      of lesional pO2. When mice were kept under normobaric hypoxia, this caused a
      persistent suppression of the lesional pO2 and a concurrent increase of the
      parasite load. In Nos2-deficient mice, there was no effect of atmospheric
      hypoxia. Low oxygen levels found at leishmanial skin lesions impaired the NOS2
      dependent leishmanicidal activity of MPhi. Hence, tissue oxygenation represents
      an underestimated local milieu factor that participates in the persistence of
      Leishmania.

PMID- 24583951
TI  - The German Critical Incident Reporting System for Anesthesiology: CIRSains.
AB  - BACKGROUND: In June 2010, the Helsinki Declaration was passed. As a result, an
      online nationwide critical incident reporting system named CIRSmedical
      Anaesthesiology (CIRSains) was implemented in Germany. The aim of the article is
      to evaluate CIRSains for practicability and to provide solutions to the problems
      detected during evaluation. METHODS: Every medical staff member could take part
      voluntarily. Data were deidentified. All reports for anesthesiology (1548) were
      taken into account. Data collection lasted from April 2010 to February 2011.
      Incident report forms were classified according to World Health Organization and
      National Patient Safety Agency taxonomy. RESULTS: Most reports (1347; 87.0%)
      contained American Society of Anaesthesiologists (ASA) classification,
      stratifying the severity of patients' underlying disease. Only some mentioned
      patients' age, even less sex. Physicians filed more reports than nurses. Staff
      related factors constituted 794 (51.3%) choices, with attention issues (433;
      28.0%) and routine violations (143; 9.2%) leading. Clinical processes (443;
      28.6%), medication (347; 22.4%), and medical devices (530; 34.2%) were the
      leading incident category types. Most consequences ranged in low (398; 25.7%) and
      moderate (826; 53.4%) risk categories. Mitigating factors were barely mentioned.
      CONCLUSION: CIRSains displays the German effort to establish the Helsinki
      declaration. Easy accessibility, anonymity, medicolegal safety, and high
      flexibility resulted in high usage. The study shows a sufficient practicability
      of the database, but the data input has to be improved for better scientific use,
      for example, by implementation of more multiple-choice questions. Given the high
      magnitude and importance of patient safety problems, improving CIRSains remains a
      priority for the future.

PMID- 24583952
TI  - The Relationship Between Patient Safety Culture and Patient Outcomes: A
      Systematic Review.
AB  - CONTEXT: In the past 13 years since the Institute of Medicine report, To Err is
      Human, was published, considerable attention was placed on the relationship
      between patient safety culture and patient outcomes. Research to understand this
      relationship has been conducted; however, now, it is important to systematically
      review these studies to determine if there are tools, levels of measure and
      outcomes that have been shown to result in significant correlations. OBJECTIVE:
      The purpose of this review is to evaluate the state of research connecting
      patient safety culture and patient outcomes to determine nurse-sensitive patient
      outcomes that have been significantly correlated to culture of safety and
      commonly used tools to measure culture of safety in the studies with significant
      correlations. DATA SOURCES: Published English only research articles were
      considered for the review. Only studies that directly measured patient outcomes
      in relationship to patient safety culture in hospitals involving registered
      nurses as a participant were included. RESULTS: Evidence of relationships between
      patient safety culture and patient outcomes exist at the hospital and nursing
      unit level of analysis; however, the number of studies finding statistically
      significant correlations particularly using nurse-sensitive outcomes is limited.
      CONCLUSIONS: The findings from this review suggest that there are emerging trends
      indicating that the specific patient safety culture measurement tools, the level
      of analysis, and selection of outcome measures are important considerations in
      study design. More research is needed to determine interventions that improve
      patient safety culture and outcomes.

PMID- 24583950
TI  - Astrocytic laminin regulates pericyte differentiation and maintains blood brain
      barrier integrity.
AB  - Blood brain barrier (BBB) breakdown is not only a consequence of but also
      contributes to many neurological disorders, including stroke and Alzheimer's
      disease. How the basement membrane (BM) contributes to the normal functioning of
      the BBB remains elusive. Here we use conditional knockout mice and an acute
      adenovirus-mediated knockdown model to show that lack of astrocytic laminin, a
      brain-specific BM component, induces BBB breakdown. Using functional blocking
      antibody and RNAi, we further demonstrate that astrocytic laminin, by binding to
      integrin alpha2 receptor, prevents pericyte differentiation from the BBB
      stabilizing resting stage to the BBB-disrupting contractile stage, and thus
      maintains the integrity of BBB. Additionally, loss of astrocytic laminin
      decreases aquaporin-4 (AQP4) and tight junction protein expression. Altogether,
      we report a critical role for astrocytic laminin in BBB regulation and pericyte
      differentiation. These results indicate that astrocytic laminin maintains the
      integrity of BBB through, at least in part, regulation of pericyte
      differentiation. 

PMID- 24583953
TI  - Who Do Hospital Physicians and Nurses Go to for Advice About Medications? A
      Social Network Analysis and Examination of Prescribing Error Rates.
AB  - OBJECTIVES: To measure the weekly medication advice-seeking networks of hospital
      staff, to compare patterns across professional groups, and to examine these in
      the context of prescribing error rates. METHOD: A social network analysis was
      conducted. All 101 staff in 2 wards in a large, academic teaching hospital in
      Sydney, Australia, were surveyed (response rate, 90%) using a detailed social
      network questionnaire. The extent of weekly medication advice seeking was
      measured by density of connections, proportion of reciprocal relationships by
      reciprocity, number of colleagues to whom each person provided advice by in
      degree, and perceptions of amount and impact of advice seeking between physicians
      and nurses. Data on prescribing error rates from the 2 wards were compared.
      RESULTS: Weekly medication advice-seeking networks were sparse (density: 7% ward
      A and 12% ward B). Information sharing across professional groups was modest, and
      rates of reciprocation of advice were low (9% ward A, 14% ward B). Pharmacists
      provided advice to most people, and junior physicians also played central roles.
      Senior physicians provided medication advice to few people. Many staff perceived
      that physicians rarely sought advice from nurses when prescribing, but almost all
      believed that an increase in communication between physicians and nurses about
      medications would improve patient safety. The medication networks in ward B had
      higher measures for density, reciprocation, and fewer senior physicians who were
      isolates. Ward B had a significantly lower rate of both procedural and clinical
      prescribing errors than ward A (0.63 clinical prescribing errors per admission
      [95%CI, 0.47-0.79] versus 1.81/ admission [95%CI, 1.49-2.13]). CONCLUSIONS:
      Medication advice-seeking networks among staff on hospital wards are limited.
      Hubs of advice provision include pharmacists, junior physicians, and senior
      nurses. Senior physicians are poorly integrated into medication advice networks.
      Strategies to improve the advice-giving networks between senior and junior
      physicians may be a fruitful area for intervention to improve medication safety.
      We found that one ward with stronger networks also had a significantly lower
      prescribing error rate, suggesting a promising area for further investigation.

PMID- 24583954
TI  - Associations of Injurious Falls and Self-Reported Incapacities: Analysis of the
      National Health Interview Survey.
AB  - PURPOSE: To determine the associative value of selected questions from the
      National Health Interview Survey (NHIS) for screening adults older than 18 years
      at risk of injurious falls. METHODS: Data from adults 18 years of age and older
      were extracted from the NHIS for 2011 relevant to an injurious fall within the
      preceding year. A multivariate logistic regression model was used to determine
      associations of self-reported injurious falls with key social-demographic,
      health, and physical function variables. Outcomes were reported as odds ratio
      (OR) with 95% confidence intervals (CIs). RESULTS: Self-reported injurious fall
      within the preceding year was associated with difficulty climbing 10 steps
      without special equipment (OR, 3.22; 95% CI, 2.32-4.46), loss of dependence for
      an activity of daily living (OR, 1.85; 95% CI, 1.17-2.91), pain in legs and below
      the knees (OR, 1.68; 95% CI, 1.23-2.30), and moderate visual impairment (OR,
      1.59; 95% CI, 1.18-2.15). Women were at greater risk than men and those aged 75
      years and older (OR, 1.46; 95% CI, 1.02-2.09). CONCLUSIONS: A subset of the NHIS
      questions are positively associated with injurious falls in the previous 12
      months and may be of use in identifying adults at greater risk of future falls.
      The NHIS questions may serve to identify persons in need of targeted preventive
      services.

PMID- 24583955
TI  - TRIAD IV: Nationwide Survey of Medical Students' Understanding of Living Wills
      and DNR Orders.
AB  - INTRODUCTION: Living wills are a form of advance directives that help to protect
      patient autonomy. They are frequently encountered in the conduct of medicine.
      Because of their impact on care, it is important to understand the adequacy of
      current medical school training in the preparation of physicians to interpret
      these directives. METHODS: Between April and August 2011 of third and fourth year
      medical students participated in an internet survey involving the interpretation
      of living wills. The survey presented a standard living will as a "stand-alone,"
      a standard living will with the addition an emergent clinical scenario and then
      variations of the standard living will that included a code status designation
      ("DNR," "Full Code," or "Comfort Care"). For each version/ scenario, respondents
      were asked to assign a code status and choose interventions based on the cases
      presented. RESULTS: Four hundred twenty-five students from medical schools
      throughout the country responded. The majority indicated they had received some
      form of advance directive training and understood the concept of code status and
      the term "DNR." Based on a stand-alone document, 15% of respondents correctly
      denoted "full code" as the appropriate code status; adding a clinical scenario
      yielded negligible improvement. When a code designation was added to the living
      will, correct code status responses ranged from 68% to 93%, whereas correct
      treatment decisions ranged from 18% to 78%. Previous training in advance
      directives had no impact on these results. CONCLUSION: Our data indicate that the
      majority of students failed to understand the key elements of a living will;
      adding a code status designations improved correct responses with the exception
      of the term DNR. Misunderstanding of advance directives is a nationwide problem
      and jeopardizes patient safety. Medical School ethics curricula need to be
      improved to ensure competency with respect to understanding advance directives.

PMID- 24583956
TI  - Integrating Data From the UK National Reporting and Learning System With Work
      Domain Analysis to Understand Patient Safety Incidents in Community Pharmacy.
AB  - OBJECTIVES: To explore the combined use of a critical incident database and work
      domain analysis to understand patient safety issues in a health-care setting.
      METHOD: A retrospective review was conducted of incidents reported to the UK
      National Reporting and Learning System (NRLS) that involved community pharmacy
      between April 2005 and August 2010. A work domain analysis of community pharmacy
      was constructed using observational data from 5 community pharmacies, technical
      documentation, and a focus group with 6 pharmacists. Reports from the NRLS were
      mapped onto the model generated by the work domain analysis. RESULTS:
      Approximately 14,709 incident reports meeting the selection criteria were
      retrieved from the NRLS. Descriptive statistical analysis of these reports found
      that almost all of the incidents involved medication and that the most frequently
      occurring error types were dose/strength errors, incorrect medication, and
      incorrect formulation. The work domain analysis identified 4 overall purposes for
      community pharmacy: business viability, health promotion and clinical services,
      provision of medication, and use of medication. These purposes were served by
      lower-order characteristics of the work system (such as the functions, processes
      and objects). The tasks most frequently implicated in the incident reports were
      those involving medication storage, assembly, or patient medication records.
      CONCLUSIONS: Combining the insights from different analytical methods improves
      understanding of patient safety problems. Incident reporting data can be used to
      identify general patterns, whereas the work domain analysis can generate
      information about the contextual factors that surround a critical task.

PMID- 24583957
TI  - Psychological safety and error reporting within Veterans Health Administration
      hospitals.
AB  - OBJECTIVE: In psychologically safe workplaces, employees feel comfortable taking
      interpersonal risks, such as pointing out errors. Previous research suggested
      that psychologically safe climate optimizes organizational outcomes. We evaluated
      psychological safety levels in Veterans Health Administration (VHA) hospitals and
      assessed their relationship to employee willingness of reporting medical errors.
      METHODS: We conducted an ANOVA on psychological safety scores from a VHA
      employees census survey (n = 185,879), assessing variability of means across
      racial and supervisory levels. We examined organizational climate assessment
      interviews (n = 374) evaluating how many employees asserted willingness to report
      errors (or not) and their stated reasons. Finally, based on survey data, we
      identified 2 (psychologically safe versus unsafe) hospitals and compared their
      number of employees who would be willing/unwilling to report an error. RESULTS:
      Psychological safety increased with supervisory level (P < 0.001, eta = 0.03) and
      was not meaningfully related to race (P < 0.001, eta = 0.003). Twelve percent of
      employees would not report an error; retaliation fear was the most commonly
      mentioned deterrent. Furthermore, employees at the psychologically unsafe
      hospital (71% would report, 13% would not) were less willing to report an error
      than at the psychologically safe hospital (91% would, 0% would not). CONCLUSIONS:
      A substantial minority would not report an error and were willing to admit so in
      a private interview setting. Their stated reasons as well as higher psychological
      safety means for supervisory employees both suggest power as an important
      determinant. Intentions to report were associated with psychological safety,
      strongly suggesting this climate aspect as instrumental to improving patient
      safety and reducing costs.

PMID- 24583958
TI  - Root Cause Analysis of Ambulatory Adverse Drug Events That Present to the
      Emergency Department.
AB  - BACKGROUND: Adverse drug events (ADEs) among patients self-administering
      medications in home/community settings are a common cause of emergency department
      (ED) visits, but the causes of these ambulatory ADEs remain unclear. Root cause
      analysis, rarely applied in outpatient settings, may reveal the underlying
      factors that contribute to adverse events. STUDY OBJECTIVES: To elicit patient
      and provider perspectives on ambulatory ADEs and apply root cause analysis
      methodology to identify cross-cutting themes among these events. METHODS:
      Emergency department clinical pharmacists screened, identified, and enrolled a
      convenience sample of adult patients 18 years or older who presented to a single,
      urban, academic ED with symptoms or diagnoses consistent with suspected ADEs.
      Semistructured phone interviews were conducted with the patients and their
      providers. We conducted a qualitative analysis. We applied a prespecified version
      of the injury prevention framework (deductive coding), identifying themes
      relating to the agent (drug), host (patient), and environment (social and health
      systems). These themes were used to construct a root cause analysis for each ADE.
      RESULTS: From 18 interviews overall, we identified the following themes within
      the injury prevention framework. Agent factors included high-risk drugs, narrow
      therapeutic indices, and uncommon severe effects. Host factors included patient
      capacity or understanding of how to use medications, awareness of side effects,
      mistrust of the medical system, patients with multiple comorbidities, difficult
      risk-benefit assessments, and high health-care users. Environmental factors
      included lack of social support, and health systems issues included access to
      care, encompassing medication availability, access to specialists, and a lack of
      continuity and communication among prescribing physicians. Root cause analysis
      revealed multiple underlying factors relating to agent, host, and environment for
      each event. CONCLUSION: Patient and physician perspectives can inform a root
      cause analysis of ambulatory ADEs. Such methodology may be applied to understand
      the factors that contribute to ambulatory ADEs and serve as the formative work
      for future interventions improving home/community medication use.

PMID- 24583959
TI  - Rapid Learning of Adverse Medical Event Disclosure and Apology.
AB  - INTRODUCTION: Despite published recommended best practices for full disclosure
      and apology to patients and families after adverse medical events, actual
      practice can be inadequate. The use of "cognitive aids" to help practitioners
      manage complex critical events has been successful in a variety of fields and
      healthcare. We wished to extend this concept to disclosure and apology events.
      The aim of this study was to test if a brief opportunity to review a best
      practice guideline for disclosure and apology would improve communication
      performance. METHODS: Thirty pairs of experienced obstetricians and labor nurses
      participated in a 3-part exercise with mixed-realism simulation. The first part
      used a standardized actor patient to meet the obstetrical team. The second part
      used a high-fidelity simulation leading to an adverse medical event (retained
      sponge), and the third part used standardized actors, patient, and husband, who
      systematically move through stages of grief response. The participants were
      randomized into 2 groups, one was provided with a cognitive aid in the form of a
      best practice guideline for disclosure and apology and the other was only given
      time to plan. Four blinded raters working in pairs scored subjects on a 7-point
      scale using a previously developed assessment instrument modified for this study.
      RESULTS: Pooled ratings of the disclosure and apology discussion for the
      intervention group (n = 167, mean = 4.9, SD = 0.92) were higher than those from
      the control group (n = 167, mean = 4.3, SD = 1.21) (P < 0.0001). One specific
      element was rated higher for the intervention group than the control group;
      posture toward the patient (n = 27, mean = 5.1, SD = 0.82 versus n = 28, mean =
      4.3, SD = 1.33) (P = 0.020). The elements of dealing with anger, dealing with
      depression, dealing with denial, bargaining, and acceptance were not different.
      CONCLUSIONS: Experienced practitioners performed better in a simulated disclosure
      and apology conversation after reviewing a cognitive aid in the form of a best
      practice guideline than a control group that was only given time to prepare.

PMID- 24583960
TI  - Shoulder dystocia documentation: an evaluation of a documentation training
      intervention.
AB  - OBJECTIVE: To evaluate the quality and content of nurse and physician shoulder
      dystocia delivery documentation before and after MORE training in shoulder
      dystocia management skills and documentation. METHODS: Approximately 384 charts
      at the Ottawa Hospital General Campus involving a diagnosis of shoulder dystocia
      between the years of 2000 and 2006 excluding the training year of 2003 were
      identified. The charts were evaluated for 14 key components derived from a
      validated instrument. The delivery notes were then scored based on these
      components by 2 separate investigators who were blinded to delivery note author,
      date, and patient identification to further quantify delivery record quality.
      RESULTS: Approximately 346 charts were reviewed for physician and nurse delivery
      documentation. The average score for physician notes was 6 (maximum possible
      score of 14) both before and after the training intervention. The nurses' average
      score was 5 before and after the training intervention. CONCLUSIONS: Negligible
      improvement was observed in the content and quality of shoulder dystocia
      documentation before and after nurse and physician training.

PMID- 24583961
TI  - Mentorship for newly appointed physicians: a strategy for enhancing patient
      safety?
AB  - OBJECTIVE: Mentorship is an increasingly popular innovation from business and
      industry that is being applied in health-care contexts. This paper explores the
      concept of mentorship for newly appointed physicians in their first substantive
      senior post, and specifically its utilization to enhance patient safety. METHODS:
      Semi-structured face to face and telephone interviews with Medical Directors (n =
      5), Deputy Medical Directors (n = 4), and Clinical Directors (n = 6) from 9 acute
      NHS Trusts in the Yorkshire and Humber region in the north of England. A focused
      thematic analysis was used. RESULTS: A number of beneficial outcomes were
      associated with mentorship for newly appointed physicians including greater
      personal and professional support, organizational commitment, and general well
      being. Providing newly appointed senior physicians with support through
      mentorship was considered to enhance the safety of patient care. Mentorship may
      prevent or reduce active failures, be used to identify threats in the local
      working environment, and in the longer term, address latent threats to safety
      within the organization by encouraging a healthier safety culture. CONCLUSIONS:
      Offering mentorship to all newly appointed physicians in their first substantive
      post in health care may be a useful strategy to support the development of their
      clinical, professional, and personal skills in this transitional period that may
      also enhance the safety of patient care.

PMID- 24583962
TI  - Glass structure responses to gamma irradiation using infrared absorption
      spectroscopy and ultrasonic techniques: a comparative study between Co2O3 and
      Fe2O3.
AB  - The response of glass to radiation was investigated using ultrasonic and FTIR
      spectroscopy. New materials were prepared from borosilicate-based glass with
      different cobalt and iron oxide compositions. The results indicate that the glass
      structures were most responsive to irradiation at 1500 Gy. Moreover, the results
      show that the radiation effect decreases when the cobalt and iron oxide
      compositions increase. These results are relevant to studies on high-dose
      processing, radio-pharmacy and storage.

PMID- 24583963
TI  - Pigments analysis and gold layer thickness evaluation of polychromy on wood
      objects by PXRF.
AB  - The X-ray fluorescence technique by energy dispersion (EDXRF), being a multi
      elemental and non-destructive technique, has been widely used in the analysis of
      artworks and archeometry. An X-ray fluorescence portable equipment from the
      Laboratory of Applied Nuclear Physics of the State University of Londrina
      (LFNA/UEL) was used for the measurement of pigments in golden parts of a Gilding
      Preparation Standard Plaque and also pigments measurement on the Wood Adornment
      of the High Altar Column of the Side Pulpit of the Immaculate Conception Church
      Parish Sao Paulo-SP. The portable X-ray fluorescence PXRF-LFNA-02 consists of an
      X-ray tube with Ag anode, a Si-PIN detector (FWHM=221 eV for Mn line at 5.9 keV),
      a chain of electronics nuclear standard of X-ray spectrometer, a multichannel 8K,
      a notebook and a mechanical system designed for the positioning of detector and X
      ray tube, which allows movements with two degrees of freedom from the system of
      excitation-detection. The excitation-detection time of each measurement was 100
      and 500 s, respectively. The presence of elements Ti, Cr, Fe, Cu, Zn and Au was
      found in the golden area of the Altar Column ornament. On the other hand,
      analysis of the ratios for the intensities of Kalpha/Kbeta lines measured in the
      areas made it possible to explore the possibility of measuring the stratigraphies
      of the layers of pigments and to estimate the thickness of the same.

PMID- 24583964
TI  - Midsagittal plane extraction from brain images based on 3D SIFT.
AB  - Midsagittal plane (MSP) extraction from 3D brain images is considered as a
      promising technique for human brain symmetry analysis. In this paper, we present
      a fast and robust MSP extraction method based on 3D scale-invariant feature
      transform (SIFT). Unlike the existing brain MSP extraction methods, which mainly
      rely on the gray similarity, 3D edge registration or parameterized surface
      matching to determine the fissure plane, our proposed method is based on
      distinctive 3D SIFT features, in which the fissure plane is determined by
      parallel 3D SIFT matching and iterative least-median of squares plane regression.
      By considering the relative scales, orientations and flipped descriptors between
      two 3D SIFT features, we propose a novel metric to measure the symmetry magnitude
      for 3D SIFT features. By clustering and indexing the extracted SIFT features
      using a k-dimensional tree (KD-tree) implemented on graphics processing units, we
      can match multiple pairs of 3D SIFT features in parallel and solve the optimal
      MSP on-the-fly. The proposed method is evaluated by synthetic and in vivo
      datasets, of normal and pathological cases, and validated by comparisons with the
      state-of-the-art methods. Experimental results demonstrated that our method has
      achieved a real-time performance with better accuracy yielding an average yaw
      angle error below 0.91 degrees  and an average roll angle error no more than 0.89
      degrees . 

PMID- 24583965
TI  - A case of fixed drug eruption secondary to quinine in tonic water presenting to a
      sexual health clinic.
AB  - Fixed drug eruption (FDE) is a cutaneous drug reaction which occurs repeatedly at
      a given mucocutaneous site after exposure to the causative agent. Lesions
      typically occur on extremities, oral mucosa and genital skin. Quinine is a common
      food additive and is recognised as a rare cause of FDE. We report a case of FDE
      with oral and genital lesions presenting to a sexual health clinic due to quinine
      contained in tonic water. 

PMID- 24583966
TI  - Chlamydia trachomatis IgG seroprevalence in the general population of the
      Netherlands in 1996 and in 2007: differential changes by gender and age.
AB  - OBJECTIVES: Chlamydia trachomatis (CT) reporting rates from sexually transmitted
      infection clinics and general practitioners have shown a rising trend in the
      Netherlands. It is unknown to what extent this reflects increased CT transmission
      or improved case finding. To achieve more insight into the CT epidemic, we
      explored the CT IgG seroprevalence (a marker of past CT infection) in the general
      population of the Netherlands in 1996 and in 2007. METHODS: From two population
      based studies in 1996 and 2007, serum samples, demographic and sexual behaviour
      outcomes were examined, including 1246 men and 1930 women aged 15-39 years. Serum
      CT IgG antibodies were analysed using the Medac CT IgG ELISA test. Multivariate
      logistic regression analyses explored the seroprevalence and determinants over
      time. RESULTS: The CT IgG seroprevalence was higher in women than in men (10% vs
      6%). Among women aged 25-39 years the seroprevalence was lower in 2007 (9%) than
      in 1996 (14%; adjusted OR (aOR) 0.6, 95% CI 0.4 to 0.8). There was no statistical
      evidence of a difference in seroprevalence within birth cohorts. Factors
      associated with seropositivity were male gender (aOR 0.4, 95% CI 0.3 to 0.7), a
      self-reported history of CT infection (aOR 5.1, 95% CI 2.6 to 10.0), age 25-39
      years (aOR 1.7, 95% CI 1.1 to 2.7), non-Western ethnicity (aOR 2.2, 95% CI 1.4 to
      3.3) and >= 2 recent sexual partners (aOR 2.2, 95% CI 1.3 to 3.5). CONCLUSIONS:
      Between 1996 and 2007 the proportion of individuals in the general population
      with CT IgG antibodies was lower among women aged 25-39 years, but remained
      similar among younger women and men.

PMID- 24583967
TI  - Disagreement of the two oscillometric blood pressure measurement devices,
      Datascope Accutorr Plus and Omron HEM-705CP II, and bidirectional conversion of
      blood pressure values.
AB  - OBJECTIVE(S): Oscillometric blood pressure (BP) measurement devices frequently
      replace the standard mercury sphygmomanometer. Comparisons of oscillometric
      devices are rare, but their agreement is important to ensure comparability of BP
      data. This study aims to compare two oscillometric devices, Datascope Accutorr
      Plus and Omron HEM-705CP II, and to develop BP conversion models. METHODS: A
      sample of 109 adults aged 21-64 years were subjected to alternate same-arm BP
      measurements according to the International Protocol revision 2010 for the
      validation of BP measuring devices in adults of the European Society of
      Hypertension. RESULTS: A total of 327 BP measurement pairs were obtained.
      Datascope systolic blood pressure (SBP) pairs, in mmHg, were optimal (<120) for
      n=188, prehypertensive (120-139) for n=107, and hypertensive (>=140) for n=32
      [diastolic blood pressure (DBP)<80 (n=261)/80-89 (n=57)/>=90 (n=9)]. The mean
      Omron values were higher and the difference increased with BP [mean differences,
      Omron minus Datascope, within BP ranges were (in mmHg): SBP 1.1+/-4.7, 3.0+/-5.5,
      and 9.3+/-6.7 and DBP 0.2+/-3.3, 2.3+/-3.4, and 5.1+/-3.9] and pulse pressure
      (>50 mmHg, SBP difference 5.6+/-6.3). The prevalence of hypertensive BP was 11%
      with Omron and 5% with Datascope. Bidirectional conversion models of SBP and DBP
      values include BP, pulse pressure, age, sex, and the difference in the ratio of
      cuff width to arm circumference. CONCLUSION: The disagreement in oscillometric
      devices can reach a magnitude that could be of interest for clinical and
      epidemiological contexts. Conversion formulas with BP, pulse pressure, sex, age,
      and the cuff width to arm circumference ratio may help to improve comparability.

PMID- 24583968
TI  - Characterization of binding between 17beta-estradiol and estriol with humic acid
      via NMR and biochemical analysis.
AB  - Endocrine disruptors, such as 17beta-estradiol (E2) and estriol (E3), are
      ubiquitously found in the environment and their presence has gained recognition
      as a significant health risk. Sorption of estrogens by dissolved organic matter
      (DOM) influences their concentration and effects. Although there is some
      experimental evidence suggesting that sorption occurs through hydrophobic
      interactions, there is not a complete understanding of this association.
      Therefore, we sought to more extensively characterize binding between humic acid
      (HA), a major component of DOM, with E2 and E3 using nuclear magnetic resonance
      spectroscopy (NMR). Our results indicate that binding between these estrogens and
      HA occurs primarily at the aromatic ring, and takes place even at relatively low
      HA concentration. Specific interactions between E2 and HA were confirmed by
      assessing binding via ELISA assay, and the effect of binding on estrogenic
      activity was studied via a yeast bioassay. Together, these studies build upon
      previously theorized interactions, yielding a more comprehensive model of binding
      between estrogens and HA, as well as demonstrate the value of the confluence of
      biochemical assay methods with analytical NMR techniques. 

PMID- 24583969
TI  - A fiber optic ammonia sensor using a universal pH indicator.
AB  - A universal pH indicator is used to fabricate a fiber optic ammonia sensor. The
      advantage of this pH indicator is that it exhibits sensitivity to ammonia over a
      broad wavelength range. This provides a differential response, with a valley
      around 500 nm and a peak around 650 nm, which allows us to perform ratiometric
      measurements. The ratiometric measurements provide not only an enhanced signal,
      but can also eliminate any external disturbance due to humidity or temperature
      fluctuations. In addition, the indicator is embedded in a hydrophobic and gas
      permeable polyurethane film named Tecoflex(r). The film provides additional
      advantages to the sensor, such as operation in dry environments, efficient
      transport of the element to be measured to the sensitive area of the sensor, and
      prevent leakage or detachment of the indicator. The combination of the universal
      pH indicator and Tecoflex(r) film provides a reliable and robust fiber optic
      ammonia sensor. 

PMID- 24583971
TI  - A multirate control strategy to the slow sensors problem: an interactive
      simulation tool for controller assisted design.
AB  - In many control applications, the sensor technology used for the measurement of
      the variable to be controlled is not able to maintain a restricted sampling
      period. In this context, the assumption of regular and uniform sampling pattern
      is questionable. Moreover, if the control action updating can be faster than the
      output measurement frequency in order to fulfill the proposed closed loop
      behavior, the solution is usually a multirate controller. There are some known
      aspects to be careful of when a multirate system (MR) is going to be designed.
      The proper multiplicity between input-output sampling periods, the proper
      controller structure, the existence of ripples and others issues need to be
      considered. A useful way to save time and achieve good results is to have an
      assisted computer design tool. An interactive simulation tool to deal with MR
      seems to be the right solution. In this paper this kind of simulation application
      is presented. It allows an easy understanding of the performance degrading or
      improvement when changing the multirate sampling pattern parameters. The tool was
      developed using Sysquake, a Matlab-like language with fast execution and powerful
      graphic facilities. It can be delivered as an executable. In the paper a detailed
      explanation of MR treatment is also included and the design of four different MR
      controllers with flexible structure to be adapted to different schemes will also
      be presented. The Smith's predictor in these MR schemes is also explained,
      justified and used when time delays appear. Finally some interesting observations
      achieved using this interactive tool are included. 

PMID- 24583970
TI  - Detection of explosives in a dynamic marine environment using a moored TNT
      immunosensor.
AB  - A field demonstration and longevity assessment for long-term monitoring of the
      explosive 2,4,6-trinitrotoluene (TNT) in a marine environment using an anti-TNT
      microfluidic immunosensor is described. The TNT immunosensor is comprised of a
      microfluidic device with 39 parallel microchannels (2.5 cm * 250 um * 500 um, L *
      W * D) fabricated in poly(methylmethacrylate) (PMMA), then chemically
      functionalized with antibodies possessing a high affinity for TNT. Synthesized
      fluorescence reporter complexes used in a displacement-based assay format were
      used for TNT identification. For field deployment the TNT immunosensor was
      configured onto a submersible moored steel frame along with frame controller,
      pumps and TNT plume generator and deployed pier side for intermittent plume
      sampling of TNT (1h increments). Under varying current and tidal conditions trace
      levels of TNT in natural seawater were detected over an extended period (>18 h).
      Overnight operation and data recording was monitored via a web interface. 

PMID- 24583972
TI  - Association between changes in 12 lifestyle behaviors and the development of
      metabolic syndrome during 1 year among workers in the Tokyo metropolitan area.
AB  - BACKGROUND: Practicing healthy lifestyle behaviors is a means to prevent
      metabolic syndrome (MetS), but the effect of changes of various behaviors over a
      short period is not fully understood. The purpose of this study was to elucidate
      the influence of changes in 12 behaviors on the development of MetS during 1
      year. METHODS AND RESULTS: Of 10,442 workers who received a periodic health
      checkup in a health center in Tokyo in 2008, 3,137 workers aged 30-69, without
      MetS, who received another health checkup in 2009 were analyzed. Smoking, amounts
      and frequency of alcohol drinking, sleeping, exercise, walking duration and
      speed, late-night dinners, bedtime snacking, breakfast, eating speed, and weight
      control were classified into 4 groups according to change from 2008 to 2009. To
      examine the influence of behavioral changes on developing MetS, multiple logistic
      analysis was conducted after adjustment for sex, baseline age and MetS
      components. Changes from healthy to unhealthy behaviors in exercise, walking
      duration and speed, daily drinking, and weight control were significant in
      developing MetS compared with maintaining healthy behaviors. Those risks were
      higher than keeping unhealthy behaviors. Unhealthy to healthy behavior in smoking
      increased the risk while healthy to unhealthy behavior in eating speed decreased
      the risk of developing MetS. CONCLUSIONS: To prevent developing MetS during 1
      year, healthy behaviors regarding physical activity, drinking, and weight
      management should be maintained.

PMID- 24583973
TI  - Early and long-term outcomes of venous stent implantation for iliac venous
      stenosis after catheter-directed thrombolysis for acute deep vein thrombosis.
AB  - BACKGROUND: Although stent implantation is used worldwide for peripheral arterial
      disease, there is little data on the safety and long-term patency of stents
      implanted for venous disease. METHODS AND RESULTS: We studied 13 patients with 14
      lesions (6 males, 7 females, mean age: 63.2+/-10.2 years) diagnosed with venous
      stenosis and who underwent venous stenting. We examined the location of the
      stenosis, safety of venous stenting, implantation success rate, and long-term
      stent patency rate. All patients were suffering from venous stenosis in the left
      common iliac vein because of iliac vein compression syndrome. No major
      complications occurred during stent implantation. Acute stent occlusion occurred
      in 1 patient, who was given additional thrombolytic therapy. Of the 13 patients,
      10 underwent venography or contrast-enhanced computed tomography (CT) during mid
      term follow-up (mean: 12.9+/-16.1 months), and only 1 stent was occluded,
      resulting in a patency rate of 90.0%. The latter patient decided to stop taking
      warfarin soon after stent implantation. Furthermore, 5 patients underwent
      contrast-enhanced CT to assess the long-term patency of their stents (mean:
      79.6+/-31.2 months), and none was occluded. CONCLUSIONS: Venous stents display a
      high long-term patency rate, and hence are a useful tool for treating iliac
      venous stenosis.

PMID- 24583974
TI  - Comparison of the axillary venous approach and subclavian venous approach for
      efficacy of permanent pacemaker implantation. 8-Year follow-up results.
AB  - BACKGROUND:  Long-term data on lead complication rates are limited for both the
      axillary and subclavian venous approaches for permanent pacemaker implantation.
      METHODS AND RESULTS:  We conducted a single-center, retrospective, nonrandomized
      comparison. We reviewed the patients who had consented to receiving a permanent
      pacemaker implant. A superficial landmark or radiographic contrast guiding was
      used for the axillary venous approach, whereas conventional landmarks were used
      for the subclavian venous approach. From January 1992 to December 2005, we
      analyzed 1,161 permanent pacemaker leads in 655 patients [subclavian venous
      approach (group I: 338 patients, 542 leads) and axillary venous approach (group
      II: 317 patients, 619 leads)]. Baseline characteristics of the patients did not
      differ. However, DDD-pacemakers and atrial leads were used more often in group II
      than in group I (94% vs. 62% and 49% vs. 40%, P<0.01). During the 8-year follow
      up, lead complication rates were lower in group II (17 leads, 3%) than in group I
      (31 leads, 6%) (P=0.03), and group II had a better complication-free survival
      curve than group I with a 49% relative risk reduction in lead complication rates
      (hazard ratio =0.51; 95% confidence interval, 0.27-0.94; P=0.03). CONCLUSIONS: 
      The axillary venous approach for permanent pacemaker implantation has better long
      term efficacy and lower lead complication rates than the subclavian venous
      approach. 

PMID- 24583975
TI  - The structure of the infectious prion protein: experimental data and molecular
      models.
AB  - The structures of the infectious prion protein, PrP(Sc), and that of its
      proteolytically truncated variant, PrP 27-30, have evaded experimental
      determination due to their insolubility and propensity to aggregate. Molecular
      modeling has been used to fill this void and to predict their structures, but
      various modeling approaches have produced significantly different models. The
      disagreement between the different modeling solutions indicates the limitations
      of this method. Over the years, in absence of a three-dimensional (3D) structure,
      a variety of experimental techniques have been used to gain insights into the
      structure of this biologically, medically, and agriculturally important isoform.
      Here, we present an overview of experimental results that were published in
      recent years, and which provided new insights into the molecular architecture of
      PrP(Sc) and PrP 27-30. Furthermore, we evaluate all published models in light of
      these recent, experimental data, and come to the conclusion that none of the
      models can accommodate all of the experimental constraints. Moreover, this
      conclusion constitutes an open invitation for renewed efforts to model the
      structure of PrP(Sc).

PMID- 24583976
TI  - OPERA: use of pegylated interferon plus ribavirin for treating HCV-HIV
      coinfection in interferon-naive patients.
AB  - BACKGROUND: The Optimized Pegylated interferons Efficacy and anti-Retroviral
      Approach (OPERA) study aimed to assess the efficacy and safety profile of
      treatment with pegylated interferons (PEG-IFNs) in interferon-naive patients with
      chronic HCV and HIV infection in routine clinical practice. METHODS: This was a
      multicentre, prospective observational cohort study conducted at 98 Italian
      referral centres for the treatment of chronic HCV and HIV coinfection. Adult
      subjects (n=1,523) with a confirmed diagnosis of HCV and stable HIV coinfection
      were followed between April 2005 and March 2011; of these, 1,284 were interferon
      naive and were the focus of this analysis. Patients received PEG-IFN-alpha2a or 
      alpha2b plus ribavirin combination therapy. The choice of treatment and dose was
      at the investigator's discretion, according to the summary of product
      characteristics and current guidelines. The primary efficacy end point was
      sustained virological response (SVR). Secondary end points included rates of
      rapid viral response, early viral response and response at end of treatment.
      RESULTS: SVR was achieved by 40.0% of patients; the highest SVR rate was observed
      in patients with HCV genotypes 2 and 3. More genotype 2 and 3 than genotype 1 and
      4 patients achieved rapid and early viral responses, and end of treatment
      responses. Higher SVR rates were also associated with >=80% anti-HCV treatment
      compliance and lower baseline HCV levels. CONCLUSIONS: The OPERA study results
      show that PEG-IFN plus ribavirin is an effective treatment for HCV-HIV
      coinfection in interferon-naive patients. Independent predictors of SVR include
      HCV genotype, undetectable baseline HIV RNA and baseline HCV RNA<500,000 IU/ml.

PMID- 24583979
TI  - Acute kidney injury: a not-so-silent disease.
AB  - Hospitalized children are experiencing acute kidney injury (AKI) with increasing
      frequency and are especially vulnerable to its long-term complications. Attempts
      to leverage novel biomarkers to improve phenotyping of this disease are limited
      by untargeted testing within broadly selected populations. Here, we review
      efforts by Basu et al. to use readily available clinical information to identify
      critically ill children at higher risk for developing severe AKI, who may benefit
      from novel diagnostic and prognostic information. 

PMID- 24583980
TI  - beta-Lapachone ameliorates murine cisplatin nephrotoxicity: NAD+, NQO1, and SIRT1
      at the crossroads of metabolism, injury, and inflammation.
AB  - The clinical utility of cisplatin is limited by nephrotoxicity. Oh et al. report
      that beta-lapachone prevents this nephrotoxicity but not cisplatin's cytotoxicity
      for cancers. In addition to its potential clinical importance, the beneficial
      effect of beta-lapachone on cisplatin acute kidney injury may illustrate
      fundamental processes that ordinarily link alterations in nutrient availability
      and intracellular reactive oxygen species on the one hand, with inflammation and
      cell death on the other hand. 

PMID- 24583981
TI  - Are serum suPAR determinations by current ELISA methodology reliable diagnostic
      biomarkers for FSGS?
AB  - A soluble proteinuric substance has been postulated as a cause of primary focal
      segmental glomerulosclerosis (FSGS), and one candidate soluble urokinase receptor
      (suPAR). Evaluation of published results shows that serum suPAR determinations by
      current methodology do not reliably distinguish FSGS from other proteinuric
      glomerular diseases and serum suPAR cannot currently be considered a valid
      biomarker for primary or secondary FSGS. However, this should not discourage
      further research on potential roles of suPAR in proteinuric renal disease,
      including FSGS. 

PMID- 24583982
TI  - Vascular calcification in chronic kidney disease: not all arteries are created
      equal.
AB  - Cardiovascular calcifications are associated with an increased cardiovascular
      risk. Different regions of the arterial tree show a variable susceptibility to
      cardiovascular calcification. O'Neill and Adams investigated breast arteries with
      vascular calcification in chronic kidney disease patients. They found no evidence
      for osteogenic transdifferentiation or apoptosis of vascular smooth muscle cells
      in these arteries, suggesting that the pathogenesis of medial calcification
      differs between arterial regions. 

PMID- 24583983
TI  - Structure, not just function.
AB  - Although kidney size can be important in the evaluation of renal disease, it has
      not been carefully studied and true volume is rarely measured, and good normative
      data are lacking. Wang et al. measured both cortical and medullary volumes in
      potential transplant donors and correlate these with physiologic, morphometric,
      and metabolic parameters. The results reveal interesting and potentially
      important correlations and differential responses between the two compartments,
      providing a framework for future investigation. 

PMID- 24583984
TI  - Cognitive impairment in chronic kidney disease: keep vascular disease in mind.
AB  - Cognitive impairment is a major cause of morbidity in people with chronic kidney
      disease (CKD) and is associated with worse survival. Prior data suggest a
      relationship between vascular disease and cognitive impairment in individuals
      with CKD. Clinicians should be aware of the high rates of cognitive impairment
      that occur in all stages of CKD, which, although sometimes subtle, may impact
      comprehension and decision making and may herald future, more debilitating
      impairment. 

PMID- 24583985
TI  - Better prevention than cure: optimal patient preparation for renal replacement
      therapy.
AB  - A generous proportion of end-stage renal disease patients may not be adequately
      prepared for initiation of renal replacement therapy (RRT). Here we review
      potential benefits of early patient referral to nephrologists and optimal
      preparation for RRT. We place this evidence in the context of the epidemiological
      study by Kurella Tamura et al., which shows that voluntary community kidney
      disease screening and education is associated with better patient preparation
      and, importantly, improved survival upon initiation of RRT. 

PMID- 24583986
TI  - Extracellular hydration, cardiovascular risk, and the interstitium: a three
      dimensional view.
AB  - Volume expansion is a major contributor to poor cardiovascular outcomes in kidney
      disease. The relationship of extracellular volume (ECV) overload to
      cardiovascular changes in chronic kidney disease (CKD) remains speculative.
      Recent studies are challenging traditional concepts and providing new insight
      into mechanisms and the relationship of ECV to cardiovascular health. A dynamic
      role of the extracellular interstitium in inducing cardiovascular risk is
      emerging in CKD. 

PMID- 24583987
TI  - Chest X-ray may serve as a screening examination for coronary artery
      calcification in dialysis patients.

PMID- 24583988
TI  - The authors reply.

PMID- 24583989
TI  - Serum suPAR concentrations in patients with focal segmental glomerulosclerosis
      with end-stage renal disease.

PMID- 24583990
TI  - The authors reply.

PMID- 24583991
TI  - The author replies.

PMID- 24583992
TI  - HDL in CKD: not protective any longer?

PMID- 24583993
TI  - Cognitive function over time in patients on chronic hemodialysis.

PMID- 24583995
TI  - The authors reply.

PMID- 24583996
TI  - Urinary angiotensinogen can be useful for screening patients with polycystic
      kidney disease.

PMID- 24583994
TI  - The authors reply.

PMID- 24583997
TI  - Trichodysplasia spinulosa.

PMID- 24583998
TI  - Widespread skin necrosis due to methotrexate overdose in a patient with CKD.

PMID- 24583999
TI  - The Case | Acute renal injury in a young Burmese immigrant. Paroxysmal nocturnal
      hemoglobinuria.

PMID- 24584000
TI  - Completeness and timeliness of vaccination and determinants for low and late
      uptake among young children in eastern China.
AB  - BACKGROUND: We studied completeness and timeliness of vaccination and
      determinants for low and delayed uptake in children born between 2008 and 2009 in
      Zhejiang province in eastern China. METHODS: We used data from a cross-sectional
      cluster survey conducted in 2011, which included 1146 children born from 1 Jan
      2008 to 31 Dec 2009. Various vaccination history, social-demographic factors,
      attitude and satisfaction toward immunization from caregivers were collected by a
      standard questionnaire. We restricted to the third dose of HepB, PV, and DPT
      (HepB3, PV3, and DPT3) as outcome variables for completeness of vaccination and
      restricted to the first dose of HepB, PV, DPT, and MCV(HepB1, PV1, DPT1, and
      MCV1) as outcome variables for timeliness of vaccination. The chi(2) test and
      logistic regression analysis were applied to identify the determinants of
      completeness and timeliness of vaccination. Survival analysis by the Kaplan-Meier
      method was performed to present the timeliness vaccination. RESULTS: Coverage for
      HepB1, HepB3, PV1, PV3, DPT1, DPT3, and MCV1 was 93.22%, 90.15%, 96.42%, 91.63%,
      95.80%, 90.16%, and 92.70%, respectively. Timely vaccination occurred in
      501/1146(43.72%) children for HepB1, 520/1146(45.38%) for PV1, 511/1146(44.59%)
      for DPT1, and 679/1146(59.25%) for MCV1. Completeness of specific vaccines was
      associated with mother' age, immigration status, birth place of child, maternal
      education level, maternal occupation status, socio-economic development level of
      surveyed areas, satisfaction toward immunization service and distance of the
      house to immunization clinic. Timeliness of vaccination for specific vaccines was
      associated with mother' age, maternal education level, immigration status,
      siblings, birth place, and distance of the house to immunization clinic.
      CONCLUSION: Despite reasonably high vaccination coverage, we observed substantial
      vaccination delays. We found specific factors associated with low and/or delayed
      vaccine uptake. These findings can help to improve strategies such as Reaching
      Every District (RED), out-reach vaccination services and health education to
      reach children who remain inadequately protected.

PMID- 24584001
TI  - Sorption of the organic cation metoprolol on silica gel from its aqueous solution
      considering the competition of inorganic cations.
AB  - Systematic batch experiments with the organic monovalent cation metoprolol as
      sorbate and the synthetic material silica gel as sorbent were conducted with the
      aim of characterizing the sorption of organic cations onto charged surfaces.
      Sorption isotherms for metoprolol (>99% protonated in the tested pH of around 6)
      in competition with mono- and divalent inorganic cations (Na(+), NH4(+), Ca(2+),
      and Mg(2+)) were determined in order to assess their influence on cation exchange
      processes and to identify the role of further sorptive interactions. The obtained
      sorption isotherms could be described well by an exponential function (Freundlich
      isotherm model) with consistent exponents (about 0.8). In general, a decreasing
      sorption of metoprolol with increasing concentrations in inorganic cations was
      observed. Competing ions of the same valence showed similar effects. A
      significant sorption affinity of metoprolol with ion type dependent Freundlich
      coefficients KF,0.77 between 234.42 and 426.58 (L/kg)(0.77) could still be
      observed even at very high concentrations of competing inorganic cations.
      Additional column experiments confirm this behavior, which suggests the existence
      of further relevant interactions beside cation exchange. In subsequent batch
      experiments, the influence of mixtures with more than one competing ion and the
      effect of a reduced negative surface charge at a pH below the point of zero
      charge (pHPZC ~ 2.5) were also investigated. Finally, the study demonstrates that
      cation exchange is the most relevant but not the sole mechanism for the sorption
      of metoprolol on silica gel. 

PMID- 24584002
TI  - Evaluation of pyrene sorption-desorption on tropical soils.
AB  - Sorption-desorption processes control soil-pollutant interactions. These
      processes determine the extent of pyrene transport in soils. Understanding
      sorption characteristics of pyrene is necessary in ascertaining its fate in soil.
      Laboratory batch experiments were conducted to study the sorptions-desorption of
      pyrene on eight soils from varying tropical agro-ecological zones (AEZs). The
      results showed that pyrene sorptions equilibria were attained within 720 min.
      Solution pH had a reciprocal effect on pyrene sorptions. Sorption was exothermic
      and increased with pyrene concentration in solution. The quantities of pyrene
      sorbed by each soil as well as the hysteresis were proportional to the percentage
      organic matter, and to some degree, the clay mineralogy. Sorption isotherms
      showed distributed reactivity involving several linear and non-linear isotherms.
      The present investigation showed that pyrene is likely to be more available to
      biota and reach the aquifer faster in low organic matter soils than those with
      relatively higher organic matter and more so in warmer climes. 

PMID- 24584003
TI  - Potential of phytoremediation for the removal of petroleum hydrocarbons in
      contaminated salt marsh sediments.
AB  - Degradation of petroleum hydrocarbons in colonized and un-colonized sediments by
      salt marsh plants Juncus maritimus and Phragmites australis collected in a
      temperate estuary was investigated during a 5-month greenhouse experiment. The
      efficiency of two bioremediation treatments namely biostimulation (BS) by the
      addition of nutrients, and bioaugmentation (BA) by addition of indigenous
      microorganisms was tested in comparison with hydrocarbon natural attenuation in
      un-colonized and with rhizoremediation in colonized sediments. Hydrocarbon
      degrading microorganisms and root biomass were assessed as well as hydrocarbon
      degradation levels. During the study, hydrocarbon degradation in un-colonized
      sediments was negligible regardless of treatments. Rhizoremediation proved to be
      an effective strategy for hydrocarbon removal, yielding high rates in most
      experiments. However, BS treatments showed a negative effect on the J. maritimus
      potential for hydrocarbon degradation by decreasing the root system development
      that lead to lower degradation rates. Although both plants and their associated
      microorganisms presented a potential for rhizoremediation of petroleum
      hydrocarbons in contaminated salt marsh sediments, results highlighted that
      nutrient requirements may be distinct among plant species, which should be
      accounted for when designing cleanup strategies. 

PMID- 24584004
TI  - Evolution of bone biomechanical properties at the micrometer scale around
      titanium implant as a function of healing time.
AB  - The characterization of the biomechanical properties of newly formed bone tissue
      around implants is important to understand the osseointegration process. The
      objective of this study is to investigate the evolution of elastic properties of
      newly formed bone tissue as a function of healing time. To do so, nanoindentation
      and micro-Brillouin scattering techniques are coupled following a multimodality
      approach using histological analysis. Coin-shaped implants were placed in vivo at
      a distance of 200 um from the cortical bone surface, leading to an initially
      empty cavity. Two rabbits were sacrificed after 7 and 13 weeks of healing time.
      The histological analyses allow us to distinguish mature and newly formed bone
      tissue. The bone mechanical properties were measured in mature and newly formed
      bone tissue. Analysis of variance and Tukey-Kramer tests reveals a significant
      effect of healing time on the indentation modulus and ultrasonic velocities of
      bone tissue. The results show that bone mass density increases by 12.2% (2.2%
      respectively) between newly formed bone at 7 weeks (13 weeks respectively) and
      mature bone. The dependence of bone properties on healing time may be explained
      by the evolution of bone microstructure and mineralization.

PMID- 24584005
TI  - [Recent topic of kansei biosensors on taste and odor sensing systems].

PMID- 24584006
TI  - [Kansei biosensors to reproduce gustatory and olfactory senses].
AB  - Anyone talks about the taste using different taste scale. Since how to feel the
      taste is different from one to other people, we sometimes lead to inconsistency
      when speaking about the taste of food. The present study aims at development of
      electronic tongue (taste sensor) and electronic nose (odor sensor). There are two
      important properties about the taste sensor. One, each sensor electrode
      (lipid/polymer membrane) is specific to each taste. Another is that the sensor
      can measure the aftertaste such as richness, which is the aftertaste of umami. In
      the case of, e.g., bitterness electrode (BT0), it responds well to bitter taste
      substances such as quinine, cetirizine, hydroxyzine and bromhexine. For other
      taste qualities, on the other hand, it shows no response. A taste sensor is now
      sold by Intelligent Sensor Technology, Inc., and utilized in pharmaceutical and
      food companies. An electronic nose to detect lingering scent is composed of
      surface plasmon resonance (SPR) sensor, which is a sensing device with high
      sensitivity, and antigen-antibody interaction. A self-assembled monolayer was
      constructed on the reception surface of SPR device. The experimental result on
      benzaldehyde, a typical peach flavor, shows the sensor sensitivity 4 ppb, which
      is superior to the human sensitivity of about 350 ppb. Our developed taste sensor
      and electronic nose play the role of gustatory and olfactory senses,
      respectively.

PMID- 24584007
TI  - [Development of taste sensor for bitterness evaluation of drugs].
AB  - In pharmaceutical fields, the palatability of drug formulation has been
      attracted, especially for children. It is excellent that pediatric medicines are
      delivered to a famine-stricken area on volunteer work. However, children cannot
      take extremely bitter drug because they are said to be highly sensitive to
      bitterness. Therefore, we contribute to the development of formulation palatable
      to children by providing pharmaceutical industry with "the measure of taste". In
      taste sensing technology, we established two methods to control the sensor's
      characteristics by optimizing both electric density and hydrophobicity of
      membrane. These innovative approaches enable the development advanced taste
      sensors to fulfill the 4 types of requirements: (1) The threshold of taste
      sensors must be the same as the human taste threshold; (2) Taste sensors must
      respond consistently to the same taste like the human tongue; (3) There must be a
      clearly defined unit of information from taste sensors; and (4) Taste sensors
      must detect interactions between taste substances.

PMID- 24584008
TI  - [Comprehensive evaluation of palatability for commercial medicine by taste
      sensing system].
AB  - The bitterness of 10 basic medicines was evaluated using a multichannel taste
      sensor (Intelligent Sensor Technology). Three variables were obtained from the
      taste sensor data: sensor output (S), the change of membrane potential caused by
      adsorption, corresponding to aftertaste (C), and the ratio C/S. These variables
      were used to predict an estimated bitterness score in multiple regression
      analysis. There was correlation between the bitterness score predicted by the
      taste sensor and the score obtained by human gustatory sensation. The method
      showed quantitative predictability for the evaluation of bitterness. Secondly,
      bitterness intensities of eight H1-antihistamines were assessed by comparing the
      Euclidean distances between the drug and water using taste sensing system Astree
      II (alpha-MOS). Two sensors were ultimately selected as best suited to bitterness
      evaluation, and the data obtained from the two sensors depicted the actual taste
      map of the eight drugs. Also the bitterness masking efficiency of epinastine
      hydrochloride with acesulfame potassium was successfully predicted. Finally,
      Vesicare((r)) tablets, whose main component is solifenacin succinate, are known
      to be extremely bitter. Recently, Vesicare((r)) orally disintegrating tablets
      (ODTs), which contain a salting-out taste-masking system, have appeared on the
      market. To evaluate the effect of crushing on the bitterness of the tablets,
      Vesicare((r)) ODTs and conventional Vesicare((r)) tablets (CTs) were crushed
      either heavily or lightly. The bitterness scores of sample solutions were
      predicted using taste sensor. The lightly crushed ODT was predicted to be less
      bitter than CT. When tablets must be crushed, it is strongly recommended that ODT
      be crushed gently.

PMID- 24584009
TI  - [Application of taste sensor to medicines in research, development and market].
AB  - Using a taste sensor in the field of medical products has the following four main
      purposes: (1) Ensuring that investigational product and placebo are
      indistinguishable; (2) Formulation design; (3) Quality control; (4) Benchmark
      test. Unlike evaluating a taste of food, roughly predicting a taste of drug
      without human sensory test and quantitative evaluation using small quantity of
      drug sample are more important than evaluation of the nuances of homogeneous
      taste and preference. Here are some examples of using taste sensor for these
      purposes. (1) We predicted a taste of suspension of phosphatic drug substance in
      an early phase of development using a taste sensor. As a result, the suspension
      seemed to have sour and bitter taste. Then we made placebo solution of citric
      acid similar taste as much like active suspension to ensure indistinguishable
      taste from each other. (2) A taste of orally disintegrating tablet (ODT) in the
      mouth is important to drug adherence. The taste of an ODT was then evaluated in
      chronological order by combining the taste sensor with the new disintegration
      testing apparatus to design easy-to-take formulation. (3) We evaluated taste
      variation of a commercial product in batch-to-batch and identified the cause of
      the variation. (4) We did benchmark test for easy-to-take of commercial ODTs in
      vitro. There is great variability among these products in the disintegrating
      profile and the taste.

PMID- 24584010
TI  - [Odor sensing system and olfactory display].
AB  - In this review, an odor sensing system and an olfactory display are introduced
      into people in pharmacy. An odor sensing system consists of an array of sensors
      with partially overlapping specificities and pattern recognition technique. One
      of examples of odor sensing systems is a halitosis sensor which quantifies the
      mixture composition of three volatile sulfide compounds. A halitosis sensor was
      realized using a preconcentrator to raise sensitivity and an electrochemical
      sensor array to suppress the influence of humidity. Partial least squares (PLS)
      method was used to quantify the mixture composition. The experiment reveals that
      the sufficient accuracy was obtained. Moreover, the olfactory display, which
      present scents to human noses, is explained. A multi-component olfactory display
      enables the presentation of a variety of smells. The two types of multi-component
      olfactory display are described. The first one uses many solenoid valves with
      high speed switching. The valve ON frequency determines the concentration of the
      corresponding odor component. The latter one consists of miniaturized liquid
      pumps and a surface acoustic wave (SAW) atomizer. It enables the wearable
      olfactory display without smell persistence. Finally, the application of the
      olfactory display is demonstrated. Virtual ice cream shop with scents was made as
      a content of interactive art. People can enjoy harmony among vision, audition and
      olfaction. In conclusion, both odor sensing system and olfactory display can
      contribute to the field of human health care.

PMID- 24584011
TI  - [The introduction of medical product's applications by using flavor and fragrance
      analyzer "FF-2020"].
AB  - The design concept of flavor and fragrance analyzer "FF-2020" was descried; at
      first how to recognize the quantification of odor, introducing traditional
      quantification of odor and how to compose the analyzer. At last two analysis of
      the medical goods were described. The most important thing to quantify the odor
      is to recognize the three faced of odor that is chemical component face,
      subjective feeling and objective feeling. For the electronic nose like a flavor
      and fragrance analyzer, objective feeling should be quantified by the analyzer.
      Then the original mode of analysis was made to realize the quantification of the
      objective feeling.

PMID- 24584012
TI  - [Academic detailing--evidence-based approach for the proper use of medicines].

PMID- 24584013
TI  - [Drug information for safe use].
AB  - Various information on pharmaceuticals is provided to healthcare professionals in
      order to ensure the safe use of pharmaceuticals. In addition to package inserts
      that contain information on indication, dosage, and administration, some review
      reports of new drugs which contain the summary of the results of clinical trials
      submitted for new drug application and review process as well as manuals for
      handling disorders due to adverse drug reactions which contain early symptoms and
      information on treatment of serious adverse reactions are provided. Information
      on drugs is renewed based on drug reactions reported to the authority. It is
      important that pharmacists comprehend this information and have the updated
      information on drugs, and disseminate this information to other healthcare
      professionals such as doctors, nurses etc. for the safe use of pharmaceuticals.
      Pharmacists who have completed a six-year course are expected to utilize all this
      information and contribute to the safe use of pharmaceuticals.

PMID- 24584014
TI  - [Academic detailing for best practice and pharmacists' role].
AB  - It is necessary to offer the proper information about prescription drugs for
      appropriate use of them in clinical practice. However, a lot of time and labor is
      required to comprehensively collect the information necessary for clinical
      application and it could be extremely difficult. If the clinical experience and
      other information is derived solely on a commercial basis, then it may lead to
      improper prescription practices. "Academic detailing" is a form of interactive
      educational outreach to physicians to provide unbiased, non-commercial, evidence
      based information about medications and other therapeutic decisions, with the
      goal of improving patient care. In Western countries, the public funds are used
      to support universities and other research institution programs. The experience
      from such programs spreads to a broader scientific community. In US, "Academic
      detailing" was pioneered 30 years ago. National Resource Center for Academic
      Detailing (NaRCAD) is an initiative supported by Agency for Healthcare Research
      and Quality (AHRQ) grant. Clinical pharmacists are acting as Detailers in Europe
      and America, and this improves medical quality. The importance of Academic
      Detailing activity would be also recognized in Japan, and fully-trained (with six
      years of specialized training) pharmacists with evaluative and communication
      skills can be expected to act as such a specialist.

PMID- 24584015
TI  - [Approach to academic detailing as a hospital pharmacist].
AB  - In 2012, a new medical fee system was introduced for the clinical activities of
      hospital pharmacists responsible for in-patient pharmacotherapy monitoring in
      medical institutions in Japan. The new medical system demands greater efforts to
      provide the most suitable and safest medicine for each patient. By applying the
      concept of academic detailing to clinical pharmacists' roles in hospitals, I
      present drug use evaluation in three disease states (peptic ulcer, insomnia, and
      osteoporosis). To analyze these from multiple aspects, we not only need knowledge
      of drug monographs (clinical and adverse drug effects), but also the ability to
      evaluate a patient's adherence and cost-effectiveness. If we combine the idea of
      academic detailing with a clinical pharmacist's role, it is necessary to
      strengthen drug information skills, such as guideline or literature search skills
      and journal evaluation. Simultaneously, it is important to introduce new
      pharmaceutical education curriculums regarding evidence-based medicine (EBM),
      pharmacoeconomics, and professional communication in order to explore
      pharmacists' roles in the future.

PMID- 24584016
TI  - [Expects for academic detailing from the standpoints of evidence-based medicine
      (EBM)].
AB  - Academic detailing, interactive information services by pharmacists for
      clinicians, has been getting interests in the US and European countries. A
      systematic review of randomized controlled trials supported the effectiveness of
      academic detailing. Knowledge of evidence-based medicine and clinical practice
      guidelines is one of the essential bases for pharmacists to promote these
      activities. In addition, pharmacists need to understand attitudes and ways of
      thinking of clinicians toward medicines. Through communications and information
      sharing between clinicians and pharmacists, collaborations to modify and improve
      the use of medicines should be facilitated. On these grounds, academic detailing
      will be able to play an important role in real healthcare circumstances.

PMID- 24584017
TI  - [Elucidation of the pathogenesis of chronic and intractable pain and its drug
      discovery].

PMID- 24584018
TI  - [Study on novel mechanism underlying analgesia targeting TRPV1].
AB  - Transient receptor potential protein (TRP) channels are distributed in pain
      pathways including primary afferent neurons and function as transduction of
      various noxious stimuli to innocuous stimuli. TRP channels are considered as
      molecular basis of chronic pain. Targeting TRPs may lead to novel class of
      analgesics, and so drug-discovery efforts are focused on TRP agonists and its
      antagonists. Few products have, however, been placed on the market, because most
      of candidates have adverse effects. A lesion or disease of the somatosensory
      nervous system causes neuropathic pain, a type of chronic pain. Neuropathic pain
      is intolerable and obstinate and therefore, debilitates the affected patients. A
      great deal of effort has been made to develop medicine targeting molecules
      involved in neuropathic pain, whereby the promising therapeutically targeted
      molecules have been identified. Neuroinflammation, based on pathological
      alteration in crosstalk between nervous system and immune system, has been a
      focus of attention as pathological mechanism involved in development of
      neuropathic pain. Recently, we used an animal model for neuropathic pain to find
      the possibility that neuropathic pain was exacerbated by adipokines derived from
      perineural adipocytes distributed in injured peripheral neurons. A working
      hypothesis is therefore proposed that the perineural adipocytes interacts with
      the immune cells, which also have TRPV1, in injured peripheral nerve, followed by
      a paracrine loop involving proinflammatory cytokines, chemokines and adipokines
      derived from them which aggravates and prolongs pain. Here, we overview the
      developmental status in TRPV1-targetting analgesics and illustrate our recent
      findings in terms of neuroinflammation.

PMID- 24584019
TI  - [Roles of transient receptor potential melastatin 2 expressed on immune cells in
      neuropathic pain].
AB  - Neuropathic pain is a pathological pain condition that often results from
      peripheral nerve injury. Several lines of evidence suggest that neuroinflammation
      mediated by the interaction between immune cells and neurons plays an important
      role in the pathogenesis of neuropathic pain. Transient receptor potential
      melastatin 2 (TRPM2) is a nonselective Ca(2+)-permeable cation channel that acts
      as a sensor for reactive oxygen species. Recent evidence suggests that TRPM2
      expressed on immune cells plays an important role in immune and inflammatory
      responses. In this study, we examined the roles of TRPM2 expressed on immune and
      glial cells in neuropathic pain. TRPM2 deficiency attenuated pain behaviors
      (mechanical allodynia, thermal hyperalgesia and spontaneous pain behaviors) in
      various kinds of inflammatory and neuropathic pain, but not in nociceptive pain
      models. In peripheral nerve injury-induced neuropathic pain models, TRPM2
      deficiency diminished infiltration of neutrophils mediated through CXCL2
      production from macrophages around the injured peripheral nerve and activation of
      spinal microglia, suggesting that TRPM2 expressed on macrophages and microglia
      aggravates peripheral and spinal pronociceptive inflammatory responses.
      Furthermore, we examined the infiltration of peripheral immune cells into the
      injured nerve and spinal cord using bone marrow chimeric mice by crossing
      wildtype and TRPM2-knockout mice. The results suggest that TRPM2 plays an
      important role in the infiltration of peripheral immune cells, particularly
      macrophages, into the spinal cord, rather than into the injured nerves. The
      spinal infiltration of macrophages mediated by TRPM2 may contribute to the
      pathogenesis of neuropathic pain.

PMID- 24584020
TI  - [Contribution of the sensitization of supraspinal nociceptive transmission in
      chronic pain].
AB  - Central sensitization in the spinal cord is well known to be involved in chronic
      pain. Recent investigations indicated that the protein expressions involving the
      synaptic plasticity are changed in several brain areas under a chronic pain
      condition. These changes in supraspinal neural function might cause the emotional
      and memory dysfunction. It is also possible that these changes are involved in
      the chronic pain. Indeed, since the improvement of spinal and peripheral
      sensitization showed limited relief in the neuropathic pain, the sensitization of
      supraspinal nociceptive transmission might be involved in the expression of
      chronic pain. We recently found that intra-thalamic treatment with excitatory
      neurotransmitter glutamate caused hyperalgesia, which is mediated by the
      stimulation of glutamate N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5
      methyl-4-isoxazolepropionic acid (AMPA) receptors. Moreover,
      intracerebroventricular treatment with gabapentin, a calcium channel alpha2delta
      1 subunit blocker, attenuated the hyperalgesia in the nerve-injury model of mice.
      These results suggest that the sensitization of supraspinal nociceptive
      transmission is involved in neuropathic pain. It is also indicated that
      neuropathic pain is resulted from the activations of spinal glial cells.
      Likewise, the supraspinal glial activation was observed in the neuropathic pain.
      Therefore, the sensitization of supraspinal nociceptive transmission might be
      important for a chronic pain. In this review, we would like to discuss the
      possible involvement of the supraspinal sensitization in neuropathic pain and in
      its application for the curative treatment in chronic pain.

PMID- 24584021
TI  - [Antinociceptive effect of docosahexaenoic acid (DHA) through long fatty acid
      receptor G protein-coupled receptor 40 (GPR40)].
AB  - Fatty acids, one class of essential nutrients for humans, are an important source
      of energy and an essential component of cell membranes. They also function as
      signal transduction molecules in a variety of biological phenomena. The important
      functional role of fatty acids in both onset and suppression of pain has become
      increasingly apparent in recent years. Recently, we have also demonstrated that
      the release of an endogenous opioid peptide, beta-endorphin, plays an important
      role in the induction of docosahexaenoic acid (DHA)-induced antinociception. It
      is well known that fatty acids affect intracellular and intercellular signaling
      as well as the membrane fluidity of neurons. In addition to intracellular
      actions, unbound free fatty acids (FFAs) can also carry out extracellular
      signaling by stimulating the G protein-coupled receptor (GPCR). Among these
      receptors, G protein-coupled receptor 40 (GPR40) has been reported to be
      activated by long-chain fatty acids such as DHA, eicosapentaenoic acid (EPA) and
      arachidonic acid. In the peripheral area, GPR40 is preferentially expressed in
      pancreatic beta-cells and is known to relate to the secretion of hormone and
      peptides. On the other hand, even though this receptor is widely distributed in
      the central nervous system, reports studying the role and functions of GPR40 in
      the brain have not been found. In this review, we summarize the findings of our
      recent study about the long-chain fatty acid receptor GPR40 as a novel pain
      regulatory system.

PMID- 24584022
TI  - [Electrophysiological evaluation of pathophysiological and pharmacological
      characteristics of chronic pain].
AB  - Recent studies have revealed considerable evidence for our understanding of the
      mechanisms underlying the development and maintenance of chronic pain including
      neuropathic and inflammatory pain. It is considered that plastic changes in the
      spinal dorsal horn contribute to the amplification of pain signaling. Moreover,
      persistent pain affects brain function and also the endogenous descending pain
      regulatory system. To characterize these pathophysiological changes and
      pharmacological properties in chronic pain conditions at the synaptic level, we
      have employed in vitro electrophysiology in slices of the spinal cord and
      supraspinal regions such as brainstem and hippocampus of adult mice and in vivo
      electrophysiology in anesthetized rats. In particular, we have successfully
      prepared spinal slices with an attached dorsal root, where A-fiber- or C-fiber
      evoked monosynaptic excitatory postsynaptic currents or miniature excitatory
      postsynaptic currents were recorded from voltage-clamped dorsal horn neurons. In
      anesthetized rats, C-fiber-evoked field potentials were recorded from the spinal
      dorsal horn in response to electrical stimulation of the sciatic nerve fibers,
      and their long-term potentiation was elicited to mimic increased synaptic
      efficacy after peripheral nerve injury. Of interest is the finding that some
      drugs exerted the injury-specific effects on synaptic transmission, thus strongly
      suggesting the importance of pharmacological analysis at the synaptic level
      combined with electrophysiological techniques to obtain pathophysiological
      information and new insights into drug research in this field.

PMID- 24584023
TI  - [Pharmaceutical analysis of chemicals related with daily life products for safe
      and secure].
AB  - An association between exposure to trace hazardous chemicals such as endocrine
      disrupting chemicals and an increased incidence of human endocrine disease might
      be continued to study. The accurate and sensitive analytical methods for
      determination of various chemicals in human biospecimen such as urine, blood and
      breast milk have been studied by techniques including chromatography. In order to
      obtain the safe and secure life, the pharmaceutical analytical approaches might
      be applicable with the hopes of realizing scientific risk assessment of the
      chemicals derived from daily life products as regulatory sciences.

PMID- 24584024
TI  - [Development of a novel transdermal delivery system of alendronate, a nitrogen
      containing bisphosphonate, using a new type of hydrophilic patch and dissolving
      microneedle arrays].
AB  - Alendronate is a nitrogen-containing bisphosphonate that is widely used for the
      treatment of osteoporosis in postmenopausal women. However, the oral
      bioavailability (BA) of alendronate is approximately 0.9 to 1.8%. In addition,
      the oral administration of alendronate has been associated with mucosal damage
      including gastritis, gastric ulcer, and erosive esophagitis. To prevent these
      adverse effects of alendronate, patients with osteoporosis should sit up or walk
      for more than 30 min after oral administration, leading to poor compliance and
      QOL in these patients. To improve the compliance and QOL of these patients, we
      developed a new transdermal delivery system for alendronate using a new type of
      hydrophilic patch and dissolving microneedle arrays. The skin permeation of
      alendronate observed using our transdermal delivery system was sufficient for the
      treatment of osteoporosis in rat models. These findings indicate that our
      transdermal delivery system of alendronate is a promising approach that may
      result in improved therapeutic effects and better compliance and QOL in patients
      undergoing treatment for osteoporosis.

PMID- 24584025
TI  - [Relationship between the effectiveness and dose of micafungin in the treatment
      of candidemia].
AB  - The Guidelines for Management of Deep-seated Mycoses 2007 recommend the use of
      micafungin as a first-line agent for the treatment of candidemia. On the package
      insert, the recommended dose of micafungin is 50 mg/d. However, the Guidelines
      recommend a micafungin dose of 100-150 mg/d. In the present study, we evaluated
      the relationship between the effectiveness and dose of micafungin in 42 patients
      with candidemia who underwent treatment with micafungin. We found that the
      efficacy rate of micafungin at a dose of 50 mg/d was 40%, whereas that at >=100
      mg/d was 87.5%. Moreover, the treatment was more effective in patients who
      received >=100 mg/d of micafungin as compared to those who received 50 mg/d of
      micafungin. Furthermore, we assessed the efficacy of micafungin according to the
      Candida species. Among all patients, the efficacy rate of micafungin was found to
      be lower in patients infected by Candida parapsilosis as compared to those
      infected by other Candida species. However, among the patients who received >=100
      mg/d of micafungin, the efficacy rate in patients infected by Candida
      parapsilosis was equivalent to that of patients who were infected by other
      Candida species. Thus, based on the results of the present study, the optimal
      micafungin dose for the treatment of candidemia appears to range from 100 to 150
      mg/d, as recommended by the Guidelines.

PMID- 24584027
TI  - Hantavirus Public Health outreach effectiveness in three populations: an overview
      of northwestern New Mexico, Los Santos Panama, and Region IX Chile.
AB  - This research compared the effectiveness of Hantavirus Pulmonary Syndrome (HPS)
      outreach programs in New Mexico, Panama, and Chile. Understanding the role of
      human demographics, disease ecology, and human behavior in the disease process is
      critical to the examination of community responses in terms of behavior changes.
      Attitudes, knowledge, and behavior across three populations were measured through
      the implementation of a self-administered questionnaire (N = 601). Surveys
      implemented in Chile and Panama in 2004, followed by northwestern New Mexico in
      2008, attempted to assess knowledge and behavior change with respect to
      hantavirus in high- and lower-risk prevalence areas during endemic periods. While
      levels of concern over contracting hantavirus were lowest in New Mexico, they
      were highest in Panama. Respondents in Chile showed mid-level concern and
      exhibited a tendency to practice proper cleaning methods more than in New Mexico
      and Panama. This indicates that public health messages appear to be more
      effective in Chile. However, since negative behavior changes, such as sweeping
      and vacuuming, occur at some level in all three populations, improved messages
      should help decrease risk of exposure to HPS. 

PMID- 24584028
TI  - Characterization of epistatic interaction of QTLs LH8 and EH3 controlling heading
      date in rice.
AB  - Heading date is a critical trait for adaptation of rice to different cultivation
      areas and cropping seasons. We evaluated the heading dates of 1,123 chromosome
      segments substitution lines (CSSLs) in the genetic background of an elite rice
      variety Huajingxian74 (HJX74). A CSSL with the substituted segments from Zihui100
      exhibited late heading under both natural long-day (NLD) and natural short-day
      (NSD) conditions, and the late heading phenotype was controlled by two novel
      epistatic loci on chromosome 8 and chromosome 3, respectively, termed LH8 and
      EH3. The function of EH3 was dependent on the LH8 genotype through epistatic
      interaction between EH3(Zihui100) and LH8(Zihui100) alleles. Genetic and
      molecular characterization revealed LH8 encodes a CCAAT-box-binding transcription
      factor with Heading date1 (Hd1)-binding activity and may delay flowering by
      repressing the expression of Early heading date1 (Ehd1). Our work provides a
      solid foundation for further study on gene interaction in heading date and has
      application in breeding rice with greater adaptability. 

PMID- 24584029
TI  - Trunk cleavage is essential for Drosophila terminal patterning and can occur
      independently of Torso-like.
AB  - Terminal patterning in Drosophila is governed by a localized interaction between
      the Torso kinase (Tor) and its ligand Trunk (Trk). Currently, it is proposed that
      Trk must be cleaved in order to bind Tor, and that these proteolytic events are
      controlled by secretion of Torso-like (Tsl) only at the embryo poles. However,
      controversy surrounds these ideas since neither cleaved Trk nor a protease that
      functions in terminal patterning have been identified. Here we show that Trk is
      cleaved multiple times in vivo and that these proteolytic events are essential
      for its function. Unexpectedly, however, the Trk cleavage patterns we observe are
      unaltered in tsl-null mutants. One explanation for these data is that the
      influence of Tsl on localized Trk cleavage at the embryo poles is subtle and
      cannot be readily detected. Alternatively, we favour a scenario where Tsl
      functions post proteolytic processing of Trk to control localized terminal
      patterning. 

PMID- 24584030
TI  - Comparison of peripheral arterial tonometry and flow-mediated vasodilation for
      assessment of the severity and complexity of coronary artery disease.
AB  - OBJECTIVE: Noninvasive flow-mediated vasodilation (FMD) is a widely used method
      to assess endothelial function, but its technical difficulty and problems remain
      obstacles for use in clinical practice. Reactive hyperemia-peripheral arterial
      tonometry (RH-PAT) was developed as a simpler and more reproducible method. We
      compared FMD and RH-PAT in patients with stable angina. Furthermore, the
      differences in these two techniques according to coronary artery disease (CAD)
      severity and complexity were also assessed. MATERIALS AND METHODS: We
      consecutively enrolled 80 patients who underwent elective coronary angiography.
      Endothelial function was assessed before angiography using brachial artery FMD
      and RH-PAT. The complexity and extent of the coronary lesions were assessed
      angiographically. The extent of CAD was defined as the number of diseased
      coronary arteries (>70%) and complexity of CAD was assessed by the SYNTAX score
      algorithm. RESULTS: In the overall study group (61+/-9 years, 57% men), the mean
      FMD was 8.5+/-5.1% and the mean reactive hyperemia index (RHI) measured by RH-PAT
      was 1.7+/-0.4. A significant correlation was observed between FMD and RHI
      irrespective of sex, diabetes, or presence of CAD. FMD and RHI were significantly
      lower in patients with multivessel and complex CAD. A receiver-operating
      characteristic curve analysis showed that both techniques were comparable in
      terms of predicting the presence of CAD and complexity. CONCLUSION: Assessment of
      RH-PAT could be a less operator-dependent and noninvasive method of evaluating
      vascular endothelial function in patients with stable angina.

PMID- 24584031
TI  - Two-year clinical outcomes of patients with overlapping second-generation drug
      eluting stents for treatment of long coronary artery lesions: comparison of
      everolimus-eluting stents with resolute zotarolimus-eluting stents.
AB  - OBJECTIVE: The aim of this study was to compare the 2-year clinical outcomes of
      overlapping second-generation everolimus-eluting stents (EES) with those of
      overlapping resolute zotarolimus-eluting stents (R-ZES) in the treatment of long
      coronary artery lesions. MATERIALS AND METHODS: This retrospective analysis
      included 256 patients treated with overlapping EES (n=121) and R-ZES (n=135) for
      long coronary artery lesions (total stent length per lesion >=34 mm). Study
      endpoints included major adverse cardiac events (MACE) defined as the composite
      of cardiac death, myocardial infarction, and target-vessel revascularization
      (TVR), as well as target-lesion revascularization and definite stent thrombosis
      separately at 2 years. RESULTS: In the two groups, the mean age was older and the
      average number of disease vessel was higher in the R-ZES group. The mean lesion
      length and total stent length per lesion were longer in the R-ZES group. EES were
      more frequently implanted in the left anterior descending coronary artery. No
      significant differences in the estimated MACE (5.8% for EES vs. 8.1% for R-ZES;
      P=0.548) or TVR (3.4% for EES vs. 4.0% for R-ZES; P=0.806) rates were noted
      between the two groups at 2-year follow-up. The incidence of definite stent
      thrombosis was low and similar in both groups (0.83% for EES vs. 0% for R-ZES;
      P=0.473). No significant differences were noted with respect to MACE or TVR
      between the two groups following propensity score matching. CONCLUSION: Stent
      overlap with second-generation EES or R-ZES was associated with low rates of
      MACE, TVR, and stent thrombosis at 2-year follow-up. Our results suggest that the
      use of overlapping EES or R-ZES in long coronary lesions is associated with good
      long-term clinical outcomes. These results need to be validated with randomized
      controlled trials.

PMID- 24584032
TI  - Endothelium-dependent vasoactivity of the human internal mammary artery.
AB  - Coronary artery disease is recognized as a major health problem worldwide,
      particularly because of the associated morbidity and mortality. Coronary artery
      bypass grafting has been an established mainstay in the treatment of this disease
      for almost half a century and is arguably the most intensively studied surgical
      procedure ever undertaken. Because of its unique properties, the human internal
      mammary artery has long been considered the best graft to use in this type of
      surgery. Previous studies have shown several advantages of this graft compared
      with others, that is, lower incidence of atherosclerosis. However, few
      comparative studies on the reactivity of this artery have been published.
      Moreover, these studies usually focus on isolated cardiovascular risk factors
      rather than combined risk factors. In fact, patients who require coronary
      revascularization usually present multiple risk factors, which can interfere with
      several pathways of regulation of vascular function, namely endothelial function.
      Several diseases and cardiovascular risk factors have been shown to interfere
      with endothelial function, promoting the production of vasoconstrictors,
      inhibiting the production of vasodilators, or both, and thus eventually leading
      to endothelial dysfunction. Therefore, it is of great interest to study the
      endothelial function, particularly of the human internal mammary artery, in the
      presence of combined cardiovascular risk factors and concomitant diseases. Many
      techniques have been developed to assess the endothelial function, in particular,
      studies on isolated arteries, as well as spectroscopic, electrochemical, and
      immunological methods, among others. 

PMID- 24584033
TI  - Mid-term results of the elastic intramedullary nailing in paediatric long bone
      shaft fractures: a prospective study of 102 cases.
AB  - The aim of this study was to evaluate the mid-term results of a large series of
      paediatric patients with long bone shaft fractures who were treated with elastic
      intramedullary nailing. Between November 2009 and November 2010, 108 long bone
      shaft fractures in 102 patients were treated with elastic intramedullary nails.
      The number of nails used, admission time, nail diameter/medullary canal diameter
      ratio of the nontraumatized extremity, weeks until radiological consolidation,
      weeks until full weight bearing for the femur and tibia shaft fractures, weeks
      until the nails were removed, number of radiographs from the diagnosis time to
      the removal time of nail(s), clinical complications and radiological results were
      recorded; the union rate, time to union, nonunion, delayed union, malrotation,
      malalignment, follow-up time and functional outcomes (Flynn outcome scoring) were
      also recorded. The mean follow-up time was 22.2 (14-30) months. The mean age of
      the patients was 9.6 (6-15) years for all cases. The mean nail removal time for
      all cases was 19.2 (17-29) weeks. Eighteen patients developed complications: six
      had insufficient reductions; two had refractures; four developed a deep
      infection; one had delayed union that needed revision; two had lower extremity
      length discrepancies of more than 15 mm; and three had skin impingements. The
      mean admission time was 19 (6-32) h; the mean number of radiographs from the
      diagnosis time to the removal time of nail(s) was 14 (8-20) for each fracture.
      All patients showed excellent or satisfactory results according to Flynn's
      criteria. The mean time to full weight bearing for the femur and tibia shaft
      fractures was 62.4 (52-88) days. A nail diameter/medullary canal diameter ratio
      of over 0.4 showed good results; short union time, less lower extremity length
      discrepancy and less malalignment were recorded. When patients were informed
      about possible complications as well as the advantages, almost all chose the
      operative approach. According to our experience and opinion, elastic
      intramedullary nailing is the best choice for diaphyseal fractures in children
      with skeletal immaturity compared with other surgical choices such as
      osteosynthesis with a plate. 

PMID- 24584034
TI  - Psychogenic limp in a child: are we aware of it?
AB  - A 10-year-old child presented with a limp for 9 months. The child was keeping his
      right knee extended and foot in the equinus position. The child had been
      investigated by numerous laboratory investigations and imaging procedures during
      the initial 9 months, but no organic cause was found. Without any conclusive
      diagnosis, the child was being managed by physical therapy. During examination in
      our clinic, the variable contraction of the quadriceps muscle raised the
      possibility of a psychiatric disorder. A psychiatrist's opinion was sought and
      the child was found to have dissociative motor disorder. His conflict was
      identified and treated by cognitive behavioral therapy. The child walked normally
      after 1 week. A psychogenic limp is often not suspected by the orthopedic surgeon
      in the evaluation of a limp. The involvement of a psychiatrist in this evaluation
      may be helpful to identify the condition easily and even at the first instance.

PMID- 24584035
TI  - MERS: emergence of a novel human coronavirus.
AB  - A novel coronavirus (CoV) that causes a severe lower respiratory tract infection
      in humans, emerged in the Middle East region in 2012. This virus, named Middle
      East respiratory syndrome (MERS)-CoV, is phylogenetically related to bat CoVs,
      but other animal species like dromedary camels may potentially act as
      intermediate hosts by spreading the virus to humans. Although human to human
      transmission has been demonstrated, analysis of human MERS clusters indicated
      that chains of transmission were not self-sustaining, especially when infection
      control was implemented. Thus, timely identification of new MERS cases followed
      by their quarantine, combined with measures to limit spread of the virus from the
      (intermediate) host to humans, may be crucial in controlling the outbreak of this
      emerging CoV. 

PMID- 24584036
TI  - Health anxiety--an indicator of higher interoceptive sensitivity?
AB  - BACKGROUND AND OBJECTIVES: According to cognitive-behavioral models, health
      anxiety arises from the misattribution of normal bodily sensations as signs of a
      severe illness. Consequently, higher levels of interoceptive accuracy might be
      critically involved in the development of health anxiety. METHODS: To test this
      central assumption of cognitive behavioral models of health anxiety, we assessed
      interoceptive accuracy in a sample of college students (N = 100). Two
      interoceptive tasks (detection of one's own heartbeat using the Schandry paradigm
      and detection of nonspecific skin conductance fluctuations, NSCFs) were used.
      RESULTS: We found no indication for a positive association between facets of
      health anxiety and a higher interoceptive accuracy in the two tasks. In fact,
      worse heartbeat perception was associated with higher health anxiety as measured
      by two questionnaires whereas perception of NSCFs was not significantly related
      to any facet of health anxiety. In addition, we found a bias to overestimate
      NSCFs in people with heightened health anxiety. LIMITATIONS: Because a sample of
      college students served as participants, the generalization of the findings is
      limited and further studies in patients with the diagnosis of hypochondriasis are
      necessary. CONCLUSIONS: The findings of both interoceptive paradigms suggest that
      health anxiety is not associated with better but rather with less accurate and
      biased interoceptive sensitivity. Probably, not a heightened interoceptive
      sensitivity but rather the bias in overestimating harmless somatic cues is more
      relevant for the maintenance of health anxiety. Our results are in line with
      recent research in other somatoform disorders.

PMID- 24584039
TI  - Zidovudine induces visceral mitochondrial toxicity and intra-abdominal fat gain
      in a rodent model of lipodystrophy.
AB  - BACKGROUND: The use of zidovudine is associated with a loss of subcutaneous
      adipose tissue (SAT). We assessed if zidovudine treatment also affects visceral
      adipose tissue (VAT) and if uridine supplementation abrogates the adverse effects
      of zidovudine on VAT. METHODS: Rats were fed zidovudine for 21 weeks with or
      without simultaneous uridine supplementation. Control animals did not receive
      zidovudine, or were treated with uridine alone. Changes in SAT and VAT were
      monitored by magnetic resonance imaging. Adipose tissue was examined for
      structural and molecular signs of mitochondrial toxicity. RESULTS: Zidovudine
      induced lipoatrophy in SAT and fat hypertrophy in VAT. Compared with controls
      zidovudine-exposed VAT adipocytes had increased diameters, microvesicular
      steatosis and enlarged mitochondria with disrupted crystal architecture on
      electron microscopy. VAT adipocyte mitochondrial DNA (mtDNA) copy numbers were
      diminished, as were mtDNA-encoded respiratory chain proteins. The 'common' mtDNA
      deletion was detected in high frequencies in zidovudine treated animals, but not
      in the controls. Although mtDNA depletion was more profound in SAT compared with
      VAT, the 'common' deletion tended to be more frequent in the VAT than in the SAT.
      Uridine coadministration abrogated all effects of zidovudine on VAT and SAT
      pathology. CONCLUSIONS: Zidovudine induces a gain of intra-abdominal fat in
      association with quantitative and qualitative alterations of the mitochondrial
      genome and impaired expression of mtDNA-encoded respiratory chain components,
      indicating that zidovudine may contribute to abdominal fat hypertrophy in HIV
      infected patients. In this rodent model, uridine supplementation abrogates both
      SAT and VAT pathology induced by zidovudine.

PMID- 24584038
TI  - The role of early-life educational quality and literacy in explaining racial
      disparities in cognition in late life.
AB  - OBJECTIVES: Racial disparities in late-life cognition persist even after
      accounting for educational attainment. We examined whether early-life educational
      quality and literacy in later life help explain these disparities. METHOD: We
      used longitudinal data from the Washington Heights-Inwood Columbia Aging Project
      (WHICAP). Educational quality (percent white students; urban/rural school;
      combined grades in classroom) was operationalized using canonical correlation
      analysis. Late-life literacy (reading comprehension and ability, writing) was
      operationalized using confirmatory factor analysis. We examined whether these
      factors attenuated race-related differences in late-life cognition. RESULTS: The
      sample consisted of 1,679 U.S.-born, non-Hispanic, community-living adults aged
      65-102 (71% black, 29% white; 70% women). Accounting for educational quality and
      literacy reduced disparities by 29% for general cognitive functioning, 26% for
      memory, and 32% for executive functioning but did not predict differences in rate
      of cognitive change. DISCUSSION: Early-life educational quality and literacy in
      late life explain a substantial portion of race-related disparities in late-life
      cognitive function.

PMID- 24584040
TI  - Hematopoietic stem cell transplantation conditioning with use of rituximab in EBV
      related lymphoproliferative disorders.
AB  - X-linked lymphoproliferative disease (XLP) and IL-2-inducible T cell kinase (ITK)
      deficiency are rare immunodeficiencies with a spectrum of clinical
      manifestations. Although there are no official guidelines for allogeneic
      hematopoietic stem cell transplantation (HSCT) in these patients, previous
      reports have shown that reduced intensity conditioning regimens provide
      successful engraftment with limited toxicity. Here, we report on three children
      with XLP and one with ITK deficiency, who underwent successful HSCT using a
      rituximab containing conditioning regimen, and review the current literature. 

PMID- 24584042
TI  - Intrarectal negative pressure system in the management of open abdomen with
      colorectal fistula: A case report.
AB  - INTRODUCTION: To present the management of open abdomen with colorectal fistula
      by application of intrarectal negative pressure system (NPS) in addition to
      abdominal NPS. PRESENTATION OF CASE: Twenty-year old man had a history of
      injuries by a close-range gunshot to the abdomen eight days ago and he had been
      treated by bowel repairs, resections, jejunal anastomosis and Hartman's
      procedure. He was referred to our center after deterioration, evisceration with
      open abdomen and enteric fistula in septic shock. There were edematous, fibrinous
      bowels and large multiple fistulas from the edematous rectal stump. APACHE II,
      Mannheim Peritoneal Index and Bjorck scores were 18, 33 and 3, respectively
      (expected mortality 100%). After intensive care for 5 days, he was treated by
      abdominal and intrarectal NPS. NPS repeated for 5 times and the fistula was
      recovered on day 18 completely. Fascial closure was facilitated with a dynamic
      abdominal closure system (ABRA) and he was discharged on day 33 uneventfully.
      There was no herniation and any other problem after 12 months follow-up.
      DISCUSSION: Management of fistula in OA can be extremely challenging. Floating
      stoma, fistula VAC, nipple VAC, ring and silo VAC, fistula intubation systems are
      used for isolation of the enteric effluent from OA. Several biologic dressings
      such as acellular dermal matrix, pedicled flaps have been used to seal the
      fistula opening with various success. Resection of the involved enteric loop and
      a new anastomosis of the intestine is very hard and rarely possible. In all of
      these reports, usually patients are left to heal with a giant hernia. In contrast
      to this, there is no hernia in our case during one year follow up period.
      CONCLUSION: Combination of intra and extra luminal negative pressure systems and
      ABRA is a safe and successful method to manage open abdomen with colorectal
      fistula.

PMID- 24584041
TI  - Progression of clinical tuberculosis is associated with a Th2 immune response
      signature in combination with elevated levels of SOCS3.
AB  - In this study, we explored the local cytokine/chemokine profiles in patients with
      active pulmonary or pleural tuberculosis (TB) using multiplex protein analysis of
      bronchoalveolar lavage and pleural fluid samples. Despite increased pro
      inflammation compared to the uninfected controls; there was no up-regulation of
      IFN-gamma or the T cell chemoattractant CCL5 in the lung of patients with
      pulmonary TB. Instead, elevated levels of IL-4 and CCL4 were associated with high
      mycobacteria-specific IgG titres as well as SOCS3 (suppressors of cytokine
      signaling) mRNA and progression of moderate-to-severe disease. Contrary, IL-4,
      CCL4 and SOCS3 remained low in patients with extrapulmonary pleural TB, while IFN
      gamma, CCL5 and SOCS1 were up-regulated. Both SOCS molecules were induced in
      human macrophages infected with Mycobacterium tuberculosis in vitro. The Th2
      immune response signature found in patients with progressive pulmonary TB could
      result from inappropriate cytokine/chemokine responses and excessive SOCS3
      expression that may represent potential targets for clinical TB management. 

PMID- 24584043
TI  - Living donor liver transplantation with replacement of vena cava for Echinococcus
      alveolaris: A case report.
AB  - INTRODUCTION: There is no medical treatment for alveolar echinococceal disease
      (AED) of liver till now. Curative surgical resection is optimal treatment but in
      most advanced cases curative resection can't be done. Liver transplantation is
      accepted treatment option for advanced AED. AED in some case invade surrounding
      tissue especially inferior vena cava (IVC). Advanced AED with invasion to IVC can
      be treated with deceased liver transplantation. Although living donor liver
      transplantation is very difficult to perform in patients with advanced AED with
      resected IVC, it come into consideration, since there is very few cadaveric
      liver. PRESENTATION OF CASE: Here we present a case with advanced stage of AED of
      liver which cause portal hypertension and cholestasis. AED invaded surrounding
      tissue, right diaphragm, both lobes of liver and retrohepatic part of IVC.
      Invasion of IVC forced us to make resection of IVC and reconstruction with
      cryopreserved venous graft to reestablish blood flow. After that a living donor
      liver transplantation was done. DISCUSSION: Curative surgery is the first-choice
      option in all operable patients with AED of liver. Advanced stage of AED like
      chronic jaundice, liver abscess, sepsis, repeated attacks of cholangitis, portal
      hypertension, and Budd-Chiari syndrome may be an indication for liver
      transplantation. In some advanced stage AED during transplantation replacement of
      retrohepatic part of IVC could be done with artificial vascular graft, cadaveric
      aortic and caval vein graft. CONCLUSION: Although living donor liver
      transplantation with replacement of IVC is a very difficult operation, it should
      be considered in the management of advanced AED of liver with IVC invasion
      because of the rarity of deceased liver.

PMID- 24584044
TI  - The 2.5-minute loaded repeated jump test: evaluating anaerobic capacity in alpine
      ski racers with loaded countermovement jumps.
AB  - The purposes of this study were to test the reproducibility of the 2.5-minute
      loaded repeated jump test (LRJT) and to test the effectiveness of general
      preparation period (GPP) training on anaerobic fitness of elite alpine ski racers
      with the LRJT. Thirteen male volunteers completed 2 LRJTs to examine reliability.
      Nine male Austrian elite junior racers were tested in June and October 2009. The
      LRJT consisted of 60 loaded countermovement jumps (LCMJs) with a loaded barbell
      equivalent to 40% bodyweight. Before the LRJT, the power (P) of a single LCMJ was
      determined. Power was calculated from ground reaction forces. The mean P was
      calculated for the complete test and for each 30-second interval. The interclass
      correlation coefficients (between 0.88 and 0.99) for main variables of the LRJT
      demonstrated a high reliability. A repeated-measures analysis of variance
      indicated that anaerobic capacity was significantly higher in October (p <=
      0.05). The ski racers' single LCMJ P increased from 37.0 +/- 1.2 W.kg to 39.0 +/-
      1.4 W.kg. The mean P of the total test improved from 33.6 +/- 1.2 W.kg to 35.8 +/
      1.3 W.kg, but relative effect of fatigue did not change. The GPP training
      improved the athletes' ability to produce and maintain muscular power. The LRJT
      is a reliable anaerobic test suitable for all alpine ski racing events because
      the 60 jumps simulate the approximate number of gates in slalom and giant slalom
      races and the 2.5 minutes is equivalent to the duration of the longest downhill
      race.

PMID- 24584045
TI  - The adolescent body image satisfaction scale for males: exploratory factor
      analysis and implications for strength and conditioning professionals.
AB  - The purpose of this study was to determine whether there is evidence of
      reliability and validity for the Adolescent Body Image Satisfaction Scale
      (ABISS), an instrument previously developed to measure adolescent body image. A
      sample (N = 330) of adolescent males, aged 14-19 years, completed the ABISS to
      determine current body image satisfaction. Data were analyzed for measures of
      instrument composite reliability and initial content and construct validity.
      Exploratory factor analysis supported a 3-factor solution (16 total items), which
      explained 42.7% of variance in the model. Composite reliability for the
      subscales, body competence, body inadequacy, and internal conflict ranged from
      0.64 to 0.82. Exploratory factor analysis of the ABISS provides initial
      psychometric support for a valid and reliable measure for assessing adolescent
      male body image, which also can be used as a needs assessment tool. Strength and
      conditioning professionals should be aware of their athlete and client
      psychological attributes, many of whom are adolescents. Understanding how
      adolescents view their bodies and their body image will assist professionals in
      designing appropriate, health-promotive strength programs, while at the same time
      monitoring for signs of body image dissatisfaction. Assessing body image can help
      heighten awareness and possibly encourage preventative programming to help avert
      negative health practices (e.g., performance-enhancing drug use, exercise
      addictions, disordered eating). The ABISS seems to have preliminary psychometric
      support to be a valid and reliable instrument that helps gauge at-risk
      populations.

PMID- 24584046
TI  - Power and impulse applied during push press exercise.
AB  - The aim of this study was to quantify the load, which maximized peak and mean
      power, and impulse applied to these loads, during the push press and to compare
      them to equivalent jump squat data. Resistance-trained men performed 2 push press
      (n = 17; age: 25.4 +/- 7.4 years; height: 183.4 +/- 5 cm; body mass: 87 +/- 15.6
      kg) and jump squat (n = 8 of original 17; age: 28.7 +/- 8.1 years; height: 184.3
      +/- 5.5 cm; mass: 98 +/- 5.3 kg) singles with 10-90% of their push press and back
      squat 1 repetition maximum (1RM), respectively, in 10% 1RM increments while
      standing on a force platform. Push press peak and mean power was maximized with
      75.3 +/- 16.4 and 64.7 +/- 20% 1RM, respectively, and impulses applied to these
      loads were 243 +/- 29 N.s and 231 +/- 36 N.s. Increasing and decreasing load,
      from the load that maximized peak and mean power, by 10 and 20% 1RM reduced peak
      and mean power by 6-15% (p <= 0.05). Push press and jump squat maximum peak power
      (7%, p = 0.08) and the impulse that was applied to the load that maximized peak
      (8%, p = 0.17) and mean (13%, p = 0.91) power were not significantly different,
      but push press maximum mean power was significantly greater than the jump squat
      equivalent (~9.5%, p = 0.03). The mechanical demand of the push press is
      comparable with the jump squat and could provide a time-efficient combination of
      lower-body power and upper-body and trunk strength training.

PMID- 24584047
TI  - Acute prior heavy strength exercise bouts improve the 20-km cycling time trial
      performance.
AB  - This study verified if a prior 5 repetition maximum (5RM) strength exercise would
      improve the cycling performance during a 20-km cycling time trial (TT20km). After
      determination of the 5RM leg press exercise load, 11 trained cyclists performed a
      TT20km in a control condition and 10-minute after 4 sets of 5RM strength exercise
      bouts (potentiation condition). Oxygen uptake, blood lactate concentration,
      ratings of perceived exertion (RPE), and power output data were recorded during
      the TT20km. Cycling economy index was assessed before the TT20km, and pacing
      strategy was analyzed assuming a "J-shaped" power output distribution profile.
      Results were a 6.1% reduction (p <= 0.05) in the time to complete the TT20km, a
      greater cycling economy (p < 0.01), and power output in the first 10% of the
      TT20km (i.e., trend; p = 0.06) in the potentiation condition. However, no
      differences were observed in pacing strategy, physiological parameters, and RPE
      between the conditions. These results suggest that 5RM strength exercise bouts
      improve the performance in a subsequent TT20km.

PMID- 24584048
TI  - Effects of muscle action type with equal impulse of conditioning activity on
      postactivation potentiation.
AB  - This study investigated the effects of muscle action type during conditioning
      activity (half-squat) on subsequent vertical jump performance. Fourteen track and
      field athletes (relative half-squat of 2.3 +/- 0.3 times their body weight)
      completed 4 main trials in a randomized and counterbalanced order 5-7 days apart:
      (a) concentric (CON) half-squats: 7.5 +/- 1.2 repetitions against 90% of 1
      repetition maximum (1RM), (b) eccentric (ECC) half-squats: 9.3 +/- 1.5
      repetitions against 70% of 1RM, and (c) 3 sets of 3-second maximal isometric
      (ISO) half-squats, (d) a control (CTRL) trial, where subjects rested for 10
      minutes. The number of repetitions in CON and ECC was adjusted so that the
      impulse of the vertical ground reaction force was similar to ISO. Countermovement
      vertical jump (CMJ) performance was evaluated for 21 minutes after each main
      trial. Countermovement vertical jump performance in ISO was higher than CTRL from
      the second to the 10th minute of recovery, whereas CMJ performance in ECC was
      higher than CTRL from the sixth and 10th minute of recovery. Analysis of the peak
      individual responses revealed an increase in CMJ performance compared with
      baseline only in ISO (3.0 +/- 1.2%; p = 0.045), whereas no significant increases
      were observed in ECC and CON. Peak CMJ performance for all subjects in ISO and
      ECC was achieved within 2-10 minutes after the conditioning muscle actions.
      Isometric were more effective than CON and ECC muscle actions in increasing
      explosive leg performance when the impulse of the ground reaction force of the
      conditioning exercise was equated.

PMID- 24584049
TI  - Neural mechanisms of dual-task interference and cognitive capacity limitation in
      the prefrontal cortex.
AB  - Simultaneous performance of two tasks often leads to performance deficits in the
      component tasks. This effect, known as dual-task interference, is thought to be a
      proof of capacity limitation in cognition, and the lateral prefrontal cortex
      (LPFC) has been highlighted as its putative neural substrate. Here we recorded
      single-neuron activities in LPFC while monkeys performed dual tasks that required
      the simultaneous performance of a varying-load spatial attention task and a
      spatial memory task. We found that the performance of the monkeys exhibited dual
      task interference, and prefrontal neuron activities showed a decreased ability to
      represent task-relevant information to a degree proportional to the increased
      demand of the concurrent counterpart task. The locus of the interference was
      shown to originate in the simultaneous, overloaded recruitment of the same LPFC
      neural population by the two tasks. These results provide direct
      neurophysiological evidence for, and constraints to, psychological models of dual
      task interference and capacity limitation. 

PMID- 24584050
TI  - Broadly tuned and respiration-independent inhibition in the olfactory bulb of
      awake mice.
AB  - Olfactory representations are shaped by brain state and respiration. The
      interaction and circuit substrates of these influences are unclear. Granule cells
      (GCs) in the main olfactory bulb (MOB) are presumed to sculpt activity reaching
      the cortex via inhibition of mitral/tufted cells (MTs). GCs potentially make
      ensemble activity more sparse by facilitating lateral inhibition among MTs and/or
      enforce temporally precise activity locked to breathing. Yet the selectivity and
      temporal structure of wakeful GC activity are unknown. We recorded GCs in the MOB
      of anesthetized and awake mice and identified state-dependent features of odor
      coding and temporal patterning. Under anesthesia, GCs were sparsely active and
      strongly and synchronously coupled to respiration. Upon waking, GCs
      desynchronized, broadened their tuning and largely fired independently from
      respiration. Thus, during wakefulness, GCs exhibited stronger odor responses with
      less temporal structure. We propose that during wakefulness GCs may shape MT odor
      responses through broadened lateral interactions rather than respiratory
      synchronization. 

PMID- 24584051
TI  - Mutant Huntingtin promotes autonomous microglia activation via myeloid lineage
      determining factors.
AB  - Huntington's disease (HD) is a fatal neurodegenerative disorder caused by an
      extended polyglutamine repeat in the N terminus of the Huntingtin protein (HTT).
      Reactive microglia and elevated cytokine levels are observed in the brains of HD
      patients, but the extent to which neuroinflammation results from extrinsic or
      cell-autonomous mechanisms in microglia is unknown. Using genome-wide approaches,
      we found that expression of mutant Huntingtin (mHTT) in microglia promoted cell
      autonomous pro-inflammatory transcriptional activation by increasing the
      expression and transcriptional activities of the myeloid lineage-determining
      factors PU.1 and C/EBPs. We observed elevated levels of PU.1 and its target genes
      in the brains of mouse models and individuals with HD. Moreover, mHTT-expressing
      microglia exhibited an increased capacity to induce neuronal death ex vivo and in
      vivo in the presence of sterile inflammation. These findings suggest a cell
      autonomous basis for enhanced microglia reactivity that may influence non-cell
      autonomous HD pathogenesis. 

PMID- 24584052
TI  - Connexin 30 sets synaptic strength by controlling astroglial synapse invasion.
AB  - Astrocytes play active roles in brain physiology by dynamic interactions with
      neurons. Connexin 30, one of the two main astroglial gap-junction subunits, is
      thought to be involved in behavioral and basic cognitive processes. However, the
      underlying cellular and molecular mechanisms are unknown. We show here in mice
      that connexin 30 controls hippocampal excitatory synaptic transmission through
      modulation of astroglial glutamate transport, which directly alters synaptic
      glutamate levels. Unexpectedly, we found that connexin 30 regulated cell adhesion
      and migration and that connexin 30 modulation of glutamate transport, occurring
      independently of its channel function, was mediated by morphological changes
      controlling insertion of astroglial processes into synaptic clefts. By setting
      excitatory synaptic strength, connexin 30 plays an important role in long-term
      synaptic plasticity and in hippocampus-based contextual memory. Taken together,
      these results establish connexin 30 as a critical regulator of synaptic strength
      by controlling the synaptic location of astroglial processes. 

PMID- 24584056
TI  - A Monte Carlo study of fluorescence generation probability in a two-layered
      tissue model.
AB  - It was recently reported that the time-resolved measurement of diffuse
      reflectance and/or fluorescence during injection of an optical contrast agent may
      constitute a basis for a technique to assess cerebral perfusion. In this paper,
      we present results of Monte Carlo simulations of the propagation of excitation
      photons and tracking of fluorescence photons in a two-layered tissue model
      mimicking intra- and extracerebral tissue compartments. Spatial 3D distributions
      of the probability that the photons were converted from excitation to emission
      wavelength in a defined voxel of the medium (generation probability) during their
      travel between source and detector were obtained for different optical properties
      in intra- and extracerebral tissue compartments. It was noted that the spatial
      distribution of the generation probability depends on the distribution of the
      fluorophore in the medium and is influenced by the absorption of the medium and
      of the fluorophore at excitation and emission wavelengths. Simulations were also
      carried out for realistic time courses of the dye concentration in both layers.
      The results of the study show that the knowledge of the absorption properties of
      the medium at excitation and emission wavelengths is essential for the
      interpretation of the time-resolved fluorescence signals measured on the surface
      of the head. 

PMID- 24584055
TI  - Provoking symptoms to relieve symptoms: a randomized controlled dismantling study
      of exposure therapy in irritable bowel syndrome.
AB  - An internet-delivered cognitive behavioral treatment (ICBT) based on systematic
      exposure exercises has previously shown beneficial effects for patients with
      irritable bowel syndrome (IBS). Exposure exercises may be perceived as difficult
      for patients to perform because of the elicited short-term distress and
      clinicians may be reluctant to use these interventions. The aim of this study was
      to compare ICBT with the same protocol without systematic exposure (ICBT-WE) to
      assess if exposure had any incremental value. This randomized controlled
      dismantling study included 309 participants diagnosed with IBS. The treatment
      interventions lasted for 10 weeks and included online therapist contact. ICBT-WE
      comprised mindfulness, work with life values, acceptance, and encouraged reduced
      avoidance behaviors, while ICBT also included systematic exposure to IBS symptoms
      and related situations. Severity of IBS symptoms was measured with the
      Gastrointestinal Symptom Rating Scale - IBS version (GSRS-IBS). The between-group
      Cohen's d on GSRS-IBS was 0.47 (95% CI: 0.23-0.70) at post-treatment and 0.48
      (95% CI: 0.20-0.76) at 6-month follow-up, favoring ICBT. We conclude that the
      systematic exposure included in the ICBT protocol has incremental effects over
      the other components in the protocol. This study provides evidence for the
      utility of exposure exercises in psychological treatments for IBS. 

PMID- 24584053
TI  - G9a influences neuronal subtype specification in striatum.
AB  - Cocaine-mediated repression of the histone methyltransferase (HMT) G9a has
      recently been implicated in transcriptional, morphological and behavioral
      responses to chronic cocaine administration. Here, using a ribosomal affinity
      purification approach, we found that G9a repression by cocaine occurred in both
      Drd1-expressing (striatonigral) and Drd2-expressing (striatopallidal) medium
      spiny neurons. Conditional knockout and overexpression of G9a within these
      distinct cell types, however, revealed divergent behavioral phenotypes in
      response to repeated cocaine treatment. Our studies further indicated that such
      developmental deletion of G9a selectively in Drd2 neurons resulted in the
      unsilencing of transcriptional programs normally specific to striatonigral
      neurons and in the acquisition of Drd1-associated projection and
      electrophysiological properties. This partial striatopallidal to striatonigral
      'switching' phenotype in mice indicates a new role for G9a in contributing to
      neuronal subtype identity and suggests a critical function for cell type-specific
      histone methylation patterns in the regulation of behavioral responses to
      environmental stimuli. 

PMID- 24584057
TI  - Tissue-resident natural killer cells.
AB  - Natural killer (NK) cells kill infected and tumor cells and produce cytokines
      that modulate other immune cells. However, most of our current knowledge is
      derived from investigations of mouse splenic and human peripheral blood NK cells,
      "conventional" NK cells. Herein we discuss recent studies indicating that the
      liver contains two subpopulations of NK cells, one of which is liver-resident and
      bears distinct markers from another liver subpopulation that resembles
      conventional NK cells. Thus, the liver and potentially other organs contain
      tissue-resident NK cells that may differ from conventional NK cells in terms of
      origin, development, and/or function. 

PMID- 24584054
TI  - Designer receptors show role for ventral pallidum input to ventral tegmental area
      in cocaine seeking.
AB  - The ventral pallidum is centrally positioned within mesocorticolimbic reward
      circuits, and its dense projection to the ventral tegmental area (VTA) regulates
      neuronal activity there. However, the ventral pallidum is a heterogeneous
      structure, and how this complexity affects its role within wider reward circuits
      is unclear. We found that projections to VTA from the rostral ventral pallidum
      (RVP), but not the caudal ventral pallidum (CVP), were robustly Fos activated
      during cue-induced reinstatement of cocaine seeking--a rat model of relapse in
      addiction. Moreover, designer receptor-mediated transient inactivation of RVP
      neurons, their terminals in VTA or functional connectivity between RVP and VTA
      dopamine neurons blocked the ability of drug-associated cues (but not a cocaine
      prime) to reinstate cocaine seeking. In contrast, CVP neuronal inhibition blocked
      cocaine-primed, but not cue-induced, reinstatement. This double dissociation in
      ventral pallidum subregional roles in drug seeking is likely to be important for
      understanding the mesocorticolimbic circuits underlying reward seeking and
      addiction.

PMID- 24584058
TI  - Control of antigen receptor diversity through spatial regulation of V(D)J
      recombination.
AB  - Lymphocytes recognize a vast variety of pathogens by expressing a diverse
      repertoire of antigen receptor genes that are assembled by V(D)J recombination in
      immature B cells (Igh, Igk) and T cells (Tcrb, Tcra/d). V(D)J recombination takes
      place in the 3' proximal domain containing the D, J, and C gene segments, whereas
      31 (Tcrb) to 200 (Igh) V genes are spread over a large region of 0.67 (Tcrb) to 3
      (Igk) Mb pairs. All antigen receptor loci undergo reversible contraction at the
      developmental stage, where they engage in V-(D)J recombination. This long-range
      looping promotes the participation of all V genes in V-(D)J recombination by
      juxtaposing distant V genes next to (D)J segments in the proximal recombination
      center. The B-cell-specific Pax5, ubiquitous YY1, and architectural CTCF/cohesin
      proteins promote Igh locus contraction in pro-B cells by binding to multiple
      sites in the VH gene cluster. These regulators also control the pro-B-cell
      specific activity of the distally located PAIR elements, which are likely
      involved in the regulation of VH-DJH recombination by mediating locus
      contraction. Notably, the large VH gene cluster of the Igh locus undergoes
      flexible long-range looping that ensures similar participation of all VH genes in
      VH-DJH recombination to generate a diverse antibody repertoire. 

PMID- 24584059
TI  - Regulation of NR4A by nutritional status, gender, postnatal development and
      hormonal deficiency.
AB  - The NR4A is a subfamily of the orphan nuclear receptors (NR) superfamily
      constituted by three well characterized members: Nur77 (NR4A1), Nurr1 (NR4A2) and
      Nor 1 (NR4A3). They are implicated in numerous biological processes as DNA
      repair, arteriosclerosis, cell apoptosis, carcinogenesis and metabolism. Several
      studies have demonstrated the role of this subfamily on glucose metabolism,
      insulin sensitivity and energy balance. These studies have focused mainly in
      liver and skeletal muscle. However, its potential role in white adipose tissue
      (WAT), one of the most important tissues involved in the regulation of energy
      homeostasis, is not well-studied. The aim of this work was to elucidate the
      regulation of NR4A in WAT under different physiological and pathophysiological
      settings involved in energy balance such as fasting, postnatal development,
      gender, hormonal deficiency and pregnancy. We compared NR4A mRNA expression of
      Nur77, Nurr1 and Nor 1 and found a clear regulation by nutritional status, since
      the expression of the 3 isoforms is increased after fasting in a leptin
      independent manner and sex steroid hormones also modulate NR4A expression in
      males and females. Our findings indicate that NR4A are regulated by different
      physiological and pathophysiological settings known to be associated with marked
      alterations in glucose metabolism and energy status. 

PMID- 24584060
TI  - The lin-4 microRNA: The ultimate micromanager.

PMID- 24584062
TI  - In-hospital mortality and long-term survival of patients with acute intoxication
      admitted to the ICU.
AB  - OBJECTIVE: To assess in-hospital and long-term mortality of Dutch ICU patients
      admitted with an acute intoxication. DESIGN: Cohort of ICU admissions from a
      national ICU registry linked to records from an insurance claims database.
      SETTING: Eighty-one ICUs (85% of all Dutch ICUs). PATIENTS: Seven thousand three
      hundred thirty-one admissions between January 1, 2008, and October 1, 2011.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Kaplan-Meier curves were used
      to compare the unadjusted mortality of the total intoxicated population and for
      specific intoxication subgroups based on the Acute Physiology and Chronic Health
      Evaluation IV reasons for admission: 1) alcohol(s), 2) analgesics, 3)
      antidepressants, 4) street drugs, 5) sedatives, 6) poisoning (carbon monoxide,
      arsenic, or cyanide), 7) other toxins, and 8) combinations. The case-mix adjusted
      mortality was assessed by the odds ratio adjusted for age, gender, severity of
      illness, intubation status, recurrent intoxication, and several comorbidities.
      The ICU mortality was 1.2%, and the in-hospital mortality was 2.1%. The mortality
      1, 3, 6, 12, and 24 months after ICU admission was 2.8%, 4.1%, 5.2%, 6.5%, and
      9.3%, respectively. Street drugs had the highest mortality 2 years after ICU
      admission (12.3%); a combination of different intoxications had the lowest
      (6.3%). The adjusted observed mortality showed that intoxications with street
      drugs and "other toxins" have a significant higher mortality 1 month after ICU
      admission (odds ratioadj = 1.63 and odds ratioadj= 1.73, respectively).
      Intoxications with alcohol or antidepressants have a significant lower mortality
      1 month after ICU admission (odds ratioadj = 0.50 and odds ratioadj = 0.46,
      respectively). These differences were not found in the adjusted mortality 3
      months upward of ICU admission. CONCLUSIONS: Overall, the mortality 2 years after
      ICU admission is relatively low compared with other ICU admissions. The first 3
      months after ICU admission there is a difference in mortality between the
      subgroups, not thereafter. Still, the difference between the in-hospital
      mortality and the mortality after 2 years is substantial.

PMID- 24584061
TI  - Leukocyte infiltration and activation of the NLRP3 inflammasome in white adipose
      tissue following thermal injury.
AB  - OBJECTIVES: Severe thermal injury is associated with extreme and prolonged
      inflammatory and hypermetabolic responses, resulting in significant catabolism
      that delays recovery or even leads to multiple organ failure and death. Burned
      patients exhibit many symptoms of stress-induced diabetes, including
      hyperglycemia, hyperinsulinemia, and hyperlipidemia. Recently, the nucleotide
      binding domain, leucine-rich family (NLR), pyrin-containing 3 (NLRP3)
      inflammasome has received much attention as the sensor of endogenous "danger
      signals" and mediator of "sterile inflammation" in type II diabetes. Therefore,
      we investigated whether the NLRP3 inflammasome is activated in the adipose tissue
      of burned patients, as we hypothesize that, similar to the scenario observed in
      chronic diabetes, the cytokines produced by the inflammasome mediate insulin
      resistance and metabolic dysfunction. DESIGN: Prospective cohort study. SETTING:
      Ross Tilley Burn Centre & Sunnybrook Research Institute. PATIENTS: We enrolled 76
      patients with burn sizes ranging from 1% to 70% total body surface area. All
      severely burned patients exhibited burn-induced insulin resistance and
      hyperglycemia. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We examined
      the adipose tissue of control and burned patients and found, via flow cytometry
      and gene expression studies, increased infiltration of leukocytes-especially
      macrophages-and evidence of inflammasome priming and activation. Furthermore, we
      observed increased levels of interleukin-1beta in the plasma of burned patients
      when compared to controls. CONCLUSIONS: In summary, our study is the first to
      show activation of the inflammasome in burned humans, and our results provide
      impetus for further investigation of the role of the inflammasome in burn-induced
      hypermetabolism and, potentially, developing novel therapies targeting this
      protein complex for the treatment of stress-induced diabetes.

PMID- 24584063
TI  - Perioperative levels and changes of high-sensitivity troponin T are associated
      with cardiovascular events in vascular surgery patients.
AB  - OBJECTIVES: Myocardial infarction after major surgery is frequent, drives
      outcome, and consumes health resources. Specific prediction and detection of
      perioperative myocardial infarction is an unmet clinical need. With the
      widespread use of high-sensitive cardiac troponin T assays, positive tests become
      frequent, but their diagnostic or prognostic impact is arguable. We, therefore,
      studied the association of routinely determined pre- and postoperative high
      sensitive cardiac troponin T with the occurrence of major adverse cardiac events.
      DESIGN: This study was a prospective non-interventional trial. SETTING: This
      study was conducted at Hannover Medical School in Germany. PATIENTS: A total of
      455 patients undergoing open vascular surgery were followed for 30 days for the
      occurrence of major adverse cardiac events. INTERVENTIONS: None. MEASUREMENTS AND
      MAIN RESULTS: Preoperative and 24-hour postoperative high-sensitive cardiac
      troponin T measurements and the respective changes were correlated to medical
      history and the occurrence of major adverse cardiac events (cardiovascular death,
      myocardial infarction, and ischemia). Pre- and postoperative high-sensitive
      cardiac troponin T measurements demonstrated a majority of patients with
      detectable troponin levels preoperatively and an increase over the 24 hours after
      surgery. The level of high-sensitive cardiac troponin T was significantly
      associated with preexisting diseases that constitute the Lee's Revised Cardiac
      Risk Index. A preoperative high-sensitive cardiac troponin T greater than or
      equal to 17.8 ng/L and a perioperative high-sensitive cardiac troponin T change
      greater than or equal to 6.3 ng/L are independently associated with the
      occurrence of major adverse cardiac events. Adding high-sensitive cardiac
      troponin T absolute change to the Revised Cardiac Risk Index improves the risk
      predictive accuracy of the score as evidenced by increased area under receiver
      operating characteristic and significant reclassification effects. CONCLUSIONS:
      The risk predictive power of high-sensitive cardiac troponin T change in addition
      to the Revised Cardiac Risk Index could facilitate 1) detection of patients at
      highest risk for perioperative myocardial ischemia, 2) evaluation and development
      of cardioprotective therapeutic strategies, and 3) decisions for admission to and
      discharge from high-density care units.

PMID- 24584064
TI  - Inducible protein-10, a potential driver of neurally controlled interleukin-10
      and morbidity in human blunt trauma.
AB  - OBJECTIVE: Blunt trauma and traumatic spinal cord injury induce systemic
      inflammation that contributes to morbidity. Dysregulated neural control of
      systemic inflammation postinjury is likely exaggerated in patients with traumatic
      spinal cord injury. We used in silico methods to discern dynamic inflammatory
      networks that could distinguish systemic inflammation in traumatic spinal cord
      injury from blunt trauma. DESIGN: Retrospective study. SETTINGS: Tertiary care
      institution. PATIENTS: Twenty-one severely injured thoracocervical traumatic
      spinal cord injury patients and matched 21 severely injured blunt trauma patients
      without spinal cord injury. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS:
      Serial blood samples were obtained from days 1 to 14 postinjury. Twenty-four
      plasma inflammatory mediators were quantified. Statistical significance between
      the two groups was determined by two-way analysis of variance. Dynamic Bayesian
      network inference was used to suggest dynamic connectivity and central
      inflammatory mediators. Circulating interleukin-10 was significantly elevated in
      thoracocervical traumatic spinal cord injury group versus non-spinal cord injury
      group, whereas interleukin-1beta, soluble interleukin-2 receptor-alpha,
      interleukin-4, interleukin-5, interleukin-7, interleukin-13, interleukin-17,
      macrophage inflammatory protein 1alpha and 1beta, granulocyte-macrophage colony
      stimulating factor, and interferon-gamma were significantly reduced in traumatic
      spinal cord injury group versus non-spinal cord injury group. Dynamic Bayesian
      network suggested that post-spinal cord injury interleukin-10 is driven by
      inducible protein-10, whereas monocyte chemotactic protein-1 was central in non
      spinal cord injury dynamic networks. In a separate validation cohorts of 356
      patients without spinal cord injury and 85 traumatic spinal cord injury patients,
      individuals with plasma inducible protein-10 levels more than or equal to 730
      pg/mL had significantly prolonged hospital and ICU stay and days on mechanical
      ventilator versus patients with plasma inducible protein-10 level less than 730
      pg/mL. CONCLUSION: This is the first study to compare the dynamic systemic
      inflammatory responses of traumatic spinal cord injury patients versus patients
      without spinal cord injury, suggesting a key role for inducible protein-10 in
      driving systemic interleukin-10 and morbidity and highlighting the potential
      utility of in silico tools to identify key inflammatory drivers.

PMID- 24584065
TI  - A scenario-based, randomized trial of patient values and functional prognosis on
      intensivist intent to discuss withdrawing life support.
AB  - OBJECTIVES: To evaluate the effect of 1) patient values as expressed by family
      members and 2) a requirement to document patients' functional prognosis on
      intensivists' intention to discuss withdrawal of life support in a hypothetical
      family meeting. DESIGN: A three-armed, randomized trial. SETTING: One hundred
      seventy-nine U.S. hospitals with training programs in critical care accredited by
      the Accreditation Council for Graduate Medical Education. SUBJECTS: Six hundred
      thirty intensivists recruited via e-mail invitation from a database of 1,850
      eligible academic intensivists. INTERVENTIONS: Each intensivist was randomized to
      review 10, online, clinical scenarios with a range of illness severities
      involving a hypothetical patient (Mrs. X). In control-group scenarios, the
      patient did not want continued life support without a reasonable chance of
      independent living. In the first experimental arm, the patient wanted life
      support regardless of functional outcome. In the second experimental arm, patient
      values were identical to the control group, but intensivists were required to
      record the patient's estimated 3-month functional prognosis. MEASUREMENTS AND
      MAIN RESULTS: Response to the question: "Would you bring up the possibility of
      withdrawing life support with Mrs. X's family?" answered using a five-point
      Likert scale. There was no effect of patient values on whether intensivists
      intended to discuss withdrawal of life support (p = 0.81), but intensivists
      randomized to record functional prognosis were 49% more likely (95% CI, 20-85%)
      to discuss withdrawal. CONCLUSIONS: In this national, scenario-based, randomized
      trial, patient values had no effect on intensivists' decisions to discuss
      withdrawal of life support with family. However, requiring intensivists to record
      patients' estimated 3-month functional outcome substantially increased their
      intention to discuss withdrawal.

PMID- 24584067
TI  - Amino acid sequence analysis in patients with chronic HCV genotype 1b infection
      during pegylated interferon-alpha2a and ribavirin therapy.
AB  - BACKGROUND: Amino acid variations in several HCV genomic regions have been
      reported to be associated with response to interferon (IFN)-alpha plus ribavirin
      (RBV) combination therapy. However, the results remain controversial. In this
      study, we further investigated the amino acid variation of full-length HCV genome
      and its correlation to the response to pegylated interferon (PEG-IFN)-alpha2a and
      RBV combination therapy in patients with HCV genotype 1b (HCV-1b). METHODS: We
      retrospectively analysed 18 chronic HCV-1b patients (9 with rapid virological
      response and 9 non-response to therapy) treated with PEG-IFN-alpha2a plus RBV for
      48 weeks. The nearly full-length HCV genome sequence was amplified by reverse
      transcription (RT)-PCR followed by cloning and sequencing. Genetic diversity
      differences between two groups were analysed including the number of amino acid
      variations in the HCV polyprotein and the mean pair-wise protein distance.
      RESULTS: No single amino acid variations were closely associated with treatment
      outcome. However, the number of amino acid mutations in the NS5B region
      especially in the thumb domain and in the NS5A-V3 region was associated with the
      response to PEG-IFN-alpha/RBV therapy (P=0.002 and P=0.029, respectively). The
      number of substitutions in the NS5B region was significantly correlated with the
      numbers of substitutions in the V3 region (r=0.568, P=0.027). CONCLUSIONS: Amino
      acid substitutions in the NS5B region especially in the thumb domain and the NS5A
      V3 region may play a role in the response to combined PEG-IFN-alpha2a and RBV
      therapy in HCV-1b patients.

PMID- 24584068
TI  - Immobilization of arsenate in a sandy loam soil using starch-stabilized magnetite
      nanoparticles.
AB  - This study investigated effectiveness of starch-stabilized magnetite
      nanoparticles for in situ enhanced sorption and immobilization of arsenate,
      As(V), in a model sandy loam soil. Batch tests showed that the nanoparticles
      offered an As(V) distribution coefficient of 10,000 L/g, which is >3 orders of
      magnitude greater than that for the soil. Batch and column experimental results
      revealed that the nanoparticle treatment greatly reduced water-leachable As(V)
      and the leachability of As(V) remaining in the soil per TCLP (Toxicity
      Characteristic Leaching Procedure) analysis. Column tests showed that water
      leachable As(V) from the As(V)-laden soil containing 31.45 mg/kg was reduced by
      ~93% and the TCLP leachability by >83% when the soil was treated with 34 pore
      volumes of a 0.1g-Fe/L of the nanoparticle suspension. While the nanoparticles
      are deliverable in the soil, the effective travel distance of the nanoparticles
      can be manipulated by controlling the injection flow rate. Under natural
      groundwater flow conditions (velocity <= 2.4 * 10(-4)cm/s), the delivered
      nanoparticles are confined within a limited distance (<6.1cm).

PMID- 24584069
TI  - Optimization of bubble column performance for nanoparticle collection.
AB  - Fibrous media embody the most effective and widely used method of separating
      ultrafine particles from a carrier fluid. The main problem associated with them
      is filter clogging, which induces an increasingly marked pressure drop with time
      and thus imposes regular media cleaning or replacement. This context has prompted
      the idea of investigating bubble columns, which operate at constant pressure
      drop, as alternatives to fibrous filters. This study examines the influence of
      different operating conditions, such as liquid height, air flow rate, bubble size
      and presence of granular beds on ultrafine particle collection. Experimental
      results show that bubble columns are characterised by high collection efficiency,
      when they feature a large liquid height and small diameter bubbling orifices,
      while their efficiencies remain lower than those of fibrous filters. Gas velocity
      does not greatly influence collection efficiency, but the inclusion of a granular
      bed, composed of beads, increases the bubble residence time in the column,
      thereby increasing the column collection efficiency. 

PMID- 24584070
TI  - A recurrent inactivating mutation in RHOA GTPase in angioimmunoblastic T cell
      lymphoma.
AB  - The molecular mechanisms underlying angioimmunoblastic T cell lymphoma (AITL), a
      common type of mature T cell lymphoma of poor prognosis, are largely unknown.
      Here we report a frequent somatic mutation in RHOA (encoding p.Gly17Val) using
      exome and transcriptome sequencing of samples from individuals with AITL. Further
      examination of the RHOA mutation encoding p.Gly17Val in 239 lymphoma samples
      showed that the mutation was specific to T cell lymphoma and was absent from B
      cell lymphoma. We demonstrate that the RHOA mutation encoding p.Gly17Val, which
      was found in 53.3% (24 of 45) of the AITL cases examined, is oncogenic in nature
      using multiple molecular assays. Molecular modeling and docking simulations
      provided a structural basis for the loss of GTPase activity in the RHOA Gly17Val
      mutant. Our experimental data and modeling results suggest that the RHOA mutation
      encoding p.Gly17Val is a driver mutation in AITL. On the basis of these data and
      through integrated pathway analysis, we build a comprehensive signaling network
      for AITL oncogenesis. 

PMID- 24584076
TI  - Development of a web course on gene therapy by the international consortium of
      gene therapy.

PMID- 24584077
TI  - A Hitchhiker's guide to the blood-brain barrier: in trans delivery of a
      therapeutic enzyme.

PMID- 24584072
TI  - An epigenetic mechanism of resistance to targeted therapy in T cell acute
      lymphoblastic leukemia.
AB  - The identification of activating NOTCH1 mutations in T cell acute lymphoblastic
      leukemia (T-ALL) led to clinical testing of gamma-secretase inhibitors (GSIs)
      that prevent NOTCH1 activation. However, responses to these inhibitors have been
      transient, suggesting that resistance limits their clinical efficacy. Here we
      modeled T-ALL resistance, identifying GSI-tolerant 'persister' cells that expand
      in the absence of NOTCH1 signaling. Rare persisters are already present in naive
      T-ALL populations, and the reversibility of their phenotype suggests an
      epigenetic mechanism. Relative to GSI-sensitive cells, persister cells activate
      distinct signaling and transcriptional programs and exhibit chromatin compaction.
      A knockdown screen identified chromatin regulators essential for persister
      viability, including BRD4. BRD4 binds enhancers near critical T-ALL genes,
      including MYC and BCL2. The BRD4 inhibitor JQ1 downregulates expression of these
      targets and induces growth arrest and apoptosis in persister cells, at doses well
      tolerated by GSI-sensitive cells. Consistently, the GSI-JQ1 combination was found
      to be effective against primary human leukemias in vivo. Our findings establish a
      role for epigenetic heterogeneity in leukemia resistance that may be addressed by
      incorporating epigenetic modulators in combination therapy. 

PMID- 24584078
TI  - From gut to brain: bioencapsulated therapeutic protein reduces amyloid load upon
      oral delivery.

PMID- 24584079
TI  - A new method for fusion, denoising and enhancement of x-ray images retrieved from
      Talbot-Lau grating interferometry.
AB  - This paper introduces a new image denoising, fusion and enhancement framework for
      combining and optimal visualization of x-ray attenuation contrast (AC),
      differential phase contrast (DPC) and dark-field contrast (DFC) images retrieved
      from x-ray Talbot-Lau grating interferometry. The new image fusion framework
      comprises three steps: (i) denoising each input image (AC, DPC and DFC) through
      adaptive Wiener filtering, (ii) performing a two-step image fusion process based
      on the shift-invariant wavelet transform, i.e. first fusing the AC with the DPC
      image and then fusing the resulting image with the DFC image, and finally (iii)
      enhancing the fused image to obtain a final image using adaptive histogram
      equalization, adaptive sharpening and contrast optimization. Application examples
      are presented for two biological objects (a human tooth and a cherry) and the
      proposed method is compared to two recently published AC/DPC/DFC image processing
      techniques. In conclusion, the new framework for the processing of AC, DPC and
      DFC allows the most relevant features of all three images to be combined in one
      image while reducing the noise and enhancing adaptively the relevant image
      features. The newly developed framework may be used in technical and medical
      applications. 

PMID- 24584080
TI  - Concentrations of selected heavy metals in maternal blood and associated factors
      in rural areas in Shanxi Province, China.
AB  - BACKGROUND: Animal experiments indicate that prenatal exposure to mercury (Hg),
      lead (Pb), cadmium (Cd) and arsenic (As) can induce fetal neural tube defects
      (NTDs). The objectives of this study were to determine the levels of maternal
      exposure to Hg, Pb, Cd and As during early pregnancy in rural areas of Shanxi
      Province, China, in order to explore factors that were associated with the
      concentrations of these metals in blood. METHODS: In 2010, we studied 215
      pregnant women during their first and second trimesters in two counties with
      different prevalence levels of NTDs in Shanxi Province, China. Demographic and
      exposure data were collected from questionnaires. Blood concentrations of Hg, Pb
      and Cd were measured with ICP-MS; the As concentration was measured using atomic
      fluorescence spectrophotometry (AFS) in whole-blood specimens. RESULTS: The
      median concentrations of Hg, Pb, Cd and As in maternal blood were 0.26 MUg/L
      (interquartile range [IQR]: 0.16-0.45), 24.48 MUg/L (IQR: 18.72-32.31), 0.47
      MUg/L (IQR: 0.33-0.67) and 0.52 MUg/L (IQR: 0.32-0.71), respectively. The
      maternal blood level of Cd was higher in Yushe county (median: 0.54 MUg/L) than
      in Daixian county (0.39 MUg/L). Women who lived near a coal combustion factory,
      used coal as cooking fuel, consumed fish, shrimp or shellfish, and consumed pork,
      beef or mutton during the week before the investigation had higher blood
      concentrations of Hg and As than their counterparts (P<0.05) after controlling
      for confounding variables, including the county of residence, in the logistic
      regression models. CONCLUSIONS: Blood levels of Cd were higher in Yushe county,
      which has a higher prevalence of neural tube defects. Higher maternal blood
      levels of Hg in pregnant women were associated with coal combustion. Higher
      maternal blood levels of Hg and As were associated with fish, shrimp or shellfish
      consumption, as well as pork, beef or mutton consumption.

PMID- 24584071
TI  - Loss-of-function mutations in SLC30A8 protect against type 2 diabetes.
AB  - Loss-of-function mutations protective against human disease provide in vivo
      validation of therapeutic targets, but none have yet been described for type 2
      diabetes (T2D). Through sequencing or genotyping of ~150,000 individuals across 5
      ancestry groups, we identified 12 rare protein-truncating variants in SLC30A8,
      which encodes an islet zinc transporter (ZnT8) and harbors a common variant
      (p.Trp325Arg) associated with T2D risk and glucose and proinsulin levels.
      Collectively, carriers of protein-truncating variants had 65% reduced T2D risk (P
      = 1.7 * 10(-6)), and non-diabetic Icelandic carriers of a frameshift variant
      (p.Lys34Serfs*50) demonstrated reduced glucose levels (-0.17 s.d., P = 4.6 * 10(
      4)). The two most common protein-truncating variants (p.Arg138* and
      p.Lys34Serfs*50) individually associate with T2D protection and encode unstable
      ZnT8 proteins. Previous functional study of SLC30A8 suggested that reduced zinc
      transport increases T2D risk, and phenotypic heterogeneity was observed in mouse
      Slc30a8 knockouts. In contrast, loss-of-function mutations in humans provide
      strong evidence that SLC30A8 haploinsufficiency protects against T2D, suggesting
      ZnT8 inhibition as a therapeutic strategy in T2D prevention.

PMID- 24584081
TI  - Seroprevalences of Toxoplasma gondii and Neospora caninum in pet rabbits in
      Japan.
AB  - The potential contamination of Toxoplasma gondii and Neospora caninum oocysts in
      the human environment is a concern from the public health viewpoint. However,
      estimation of their seroprevalences in humans cannot be performed in a manner
      that distinguishes between oocysts and tissue cysts as a source of infection.
      Rabbits are considered popular pet animals in Japan that can acquire natural
      infections by the aforementioned parasites only through the ingestion of oocysts.
      Therefore, this study was conducted to estimate the seroprevalences of T. gondii
      and N. caninum in pet rabbits in Japan as an indicator of the possible oocyst
      contamination in the environment surrounding human beings. Serum samples of 337
      rabbits were examined by different serological methods. Enzyme-linked
      immunosorbent assays were performed to measure the titer of IgG and IgM
      antibodies. Samples revealed to be seropositive by ELISA were further analyzed by
      a latex agglutination test, Western blotting and an indirect immunofluorescence
      assay. The rates of seropositivity for T. gondii were 0.89% (3/337) and 0.29%
      (1/337) in IgG and IgM ELISA, respectively. SAG1 and SAG2 were detected as major
      antigens by the positive rabbit sera in Western blotting associated with strong
      staining observed by IFA in T. gondii tachyzoites. Regarding N. caninum, none of
      the serum samples showed a specific reaction in both Western blotting and the
      IFA. The results of this study indicate low seroprevalences of toxoplasmosis and
      neosporosis in pet rabbits in Japan, suggesting low oocyst contamination in the
      human environment. 

PMID- 24584082
TI  - New visible endotracheal intubation method using the endoscope system for mice
      inhalational anesthesia.
AB  - Appropriate and effective anesthesia is critical, because it has a strong
      influence on laboratory animals, and its affect greatly impacts the experimental
      data. Inhalational anesthesia by endotracheal intubation is currently prevailing
      in general anesthesia and is prefered over injection anesthesia, especially for
      large laboratory animals, because it is a safe and easy control agent. However,
      it is not common for small laboratory animals, because of the high degree of
      technical skills required. We assessed the capability of use for mice of the
      endotracheal intubation by using the endoscope system "TESALA AE-C1" and
      inhalational anesthesia using a ventilator. Endotracheal intubation was
      successfully performed on all 10 C57BL/6 mice injected with M/M/B: 0.3/4/5
      comprised of medetomidine, midazoram and butorphanol, at a dose of 0.3 mg/kg +
      4.0 mg/kg + 5.0 mg/kg body weight/mouse, respectively. After the intubated mice
      were connected with the inhalational anesthesia circuit and the ventilator, vital
      signs were measured until 15 min after the connection. The data with M/M/B:
      0.3/4/5 showed stable and normal values, which indicated that this new
      endotracheal intubation method was simple, reliable and safe, which mean that
      this anesthesia is favorable in regard to the animal's welfare. 

PMID- 24584083
TI  - Anesthetic effect of a combination of medetomidine-midazolam-butorphanol in
      cynomolgus monkeys (Macaca fascicularis).
AB  - The anesthetic effect of a combination of medetomidine, midazolam and butorphanol
      (Me-Mi-Bu) was evaluated in healthy cynomolgus monkeys. The Me-Mi-Bu combination
      was intramuscularly administered as follows: Dose 1, Me 0.015 mg/kg-Mi 0.1 mg/kg
      Bu 0.15 mg/kg; Dose 2, Me 0.02 mg/kg-Mi 0.15 mg/kg-Bu 0.2 mg/kg; and Dose 3, Me
      0.04 mg/kg-Mi 0.3 mg/kg-Bu 0.4 mg/kg. The combination rapidly induced
      immobilization, and lateral recumbency was reached within 15 min. The duration of
      anesthesia for each dose administered was follows: Dose 1, 47 +/- 27 min; Dose 2,
      113 +/- 31 min; and Dose 3, 190 +/- 24 min. The anesthetic effect of the
      combination was abolished by the alpha2-adrenoceptor antagonist atipamezole. No
      marked changes in the levels of hematologic or serum biochemical parameters were
      noted in cynomolgus monkeys administered the combination plus atipamezole. Taken
      together, these results suggest that the Me-Mi-Bu combination exhibits reversible
      anesthetic effect and may be useful for studies involving cynomolgus monkeys. 

PMID- 24584084
TI  - Collection, integration and analysis of cancer genomic profiles: from data to
      insight.
AB  - The recent deluge of cancer genomics data provides a tremendous opportunity for
      the discovery of detailed mechanisms of tumorigenesis and the development of
      therapeutics. However, identifying the functionally relevant genomic alterations
      ('drivers') among the many non-oncogenic events ('passengers') presents a major
      challenge. Several new methods have been developed over the past few years that
      identify recurrently altered genes. Mapping the recurrent genomic alterations,
      such as somatic mutations and focal DNA copy-number alterations, onto individual
      tumor samples as tumor-specific event calls facilitates the identification of
      altered processes and pathways. The resulting reduction in complexity makes
      cancer genomics data more easily interpretable by cancer researchers and is now
      driving the development of powerful yet intuitive web-based analysis tools. 

PMID- 24584086
TI  - HCV RNA quantification with different assays: implications for protease-inhibitor
      based response-guided therapy.
AB  - BACKGROUND: Response-guided therapy (RGT) for HCV treatment, whereby therapy
      duration is shortened according to on-treatment virological response, requires
      patient HCV RNA concentrations below the lower limit of quantification (LLOQ) or
      limit of detection (LOD) of the viral load assay at weeks 4 and 12. Concordance
      of two assays and impact on treatment decisions were investigated. METHODS:
      Plasma samples (n=1,411; baseline to week 12) from HCV genotype-1-infected
      patients (n=290) receiving simeprevir (TMC435) plus pegylated interferon
      alpha2a/ribavirin in the PILLAR study (NCT00882908) were analysed using Roche
      High-Pure-System/COBAS((r)) TaqMan((r)) v2.0 assay (HPS; LLOQ 25 IU/ml and LOD 15
      IU/ml; Roche Diagnostics, Indianapolis, IN, USA) and reanalysed using Abbott
      realtime assay (ART; LLOQ and LOD 12 IU/ml; Abbott Molecular Inc., Des Plaines,
      IL, USA). RESULTS: Overall, 217/766 (28.3%) samples from different time points
      with HCV RNA undetectable by HPS had HCV RNA detectable by ART. Conversely,
      35/584 (6.0%) samples undetectable by ART were detectable by HPS. For both
      assays, most discrepant samples (96-100%) had HCV RNA<25 IU/ml. At week 4, 75.5%
      of samples were undetectable by HPS, whereas 49.4% were undetectable by ART,
      resulting in different RGT assessment in 26.1% (P<0.0001). At week 12, 95.4% and
      91.9% of samples were undetectable with HPS and ART, respectively. CONCLUSIONS:
      Lower rates of undetectable HCV RNA with ART at week 4 suggest that if RGT
      criteria are determined with ART, the proportion of patients qualifying for
      shorter treatment duration may be significantly lower (26%). Therefore, different
      RGT criteria may be necessary for ART to maximize numbers benefiting from
      shortened treatment. Further testing and validation are required.

PMID- 24584085
TI  - Malondialdehyde-derived epitopes in human skin result from acute exposure to
      solar UV and occur in nonmelanoma skin cancer tissue.
AB  - Cutaneous exposure to solar ultraviolet radiation (UVR) is a causative factor in
      photoaging and photocarcinogenesis. In human skin, oxidative stress is widely
      considered a key mechanism underlying the detrimental effects of acute and
      chronic UVR exposure. The lipid peroxidation product malondialdehyde (MDA)
      accumulates in tissue under conditions of increased oxidative stress, and the
      occurrence of MDA-derived protein epitopes, including dihydropyridine-lysine
      (DHP), has recently been substantiated in human skin. Here we demonstrate for the
      first time that acute exposure to sub-apoptogenic doses of solar simulated UV
      light (SSL) causes the formation of free MDA and protein-bound MDA-derived
      epitopes in cultured human HaCaT keratinocytes and healthy human skin.
      Immunohistochemical staining revealed that acute exposure to SSL is sufficient to
      cause an almost twenty-fold increase in general MDA- and specific DHP-epitope
      content in human skin. When compared to dose-matched solar simulated UVA,
      complete SSL was more efficient generating both free MDA and MDA-derived
      epitopes. Subsequent tissue microarray (TMA) analysis revealed the prevalence of
      MDA- and DHP-epitopes in nonmelanoma skin cancer (NMSC). In squamous cell
      carcinoma tissue, both MDA- and DHP-epitopes were increased more than threefold
      as compared to adjacent normal tissue. Taken together, these date demonstrate the
      occurrence of MDA-derived epitopes in both solar UVR-exposed healthy human skin
      and NMSC TMA tissue; however, the potential utility of these epitopes as novel
      biomarkers of cutaneous photodamage and a functional role in the process of skin
      photocarcinogenesis remain to be explored. 

PMID- 24584087
TI  - Size and symmetry of the superconducting gap in the f.c.c. Cs3C60 polymorph close
      to the metal-Mott insulator boundary.
AB  - The alkali fullerides, A(3)C(60) (A = alkali metal) are molecular superconductors
      that undergo a transition to a magnetic Mott-insulating state at large lattice
      parameters. However, although the size and the symmetry of the superconducting
      gap, Delta, are both crucial for the understanding of the pairing mechanism, they
      are currently unknown for superconducting fullerides close to the correlation
      driven magnetic insulator. Here we report a comprehensive nuclear magnetic
      resonance (NMR) study of face-centred-cubic (f.c.c.) Cs(3)C(60) polymorph, which
      can be tuned continuously through the bandwidth-controlled Mott insulator
      metal/superconductor transition by pressure. When superconductivity emerges from
      the insulating state at large interfullerene separations upon compression, we
      observe an isotropic (s-wave) Delta with a large gap-to-superconducting
      transition temperature ratio, 2Delta0/k(B)T(c) = 5.3(2) [Delta0 = Delta(0 K)].
      2Delta0/k(B)T(c) decreases continuously upon pressurization until it approaches a
      value of ~3.5, characteristic of weak-coupling BCS theory of superconductivity
      despite the dome-shaped dependence of Tc on interfullerene separation. The
      results indicate the importance of the electronic correlations for the pairing
      interaction as the metal/superconductor-insulator boundary is approached.

PMID- 24584088
TI  - Early specification of CD8+ T lymphocyte fates during adaptive immunity revealed
      by single-cell gene-expression analyses.
AB  - T lymphocytes responding to microbial infection give rise to effector cells that
      mediate acute host defense and memory cells that provide long-lived immunity, but
      the fundamental question of when and how these cells arise remains unresolved.
      Here we combined single-cell gene-expression analyses with 'machine-learning'
      approaches to trace the transcriptional 'roadmap' of individual CD8(+) T
      lymphocytes throughout the course of an immune response in vivo. Gene-expression
      signatures predictive of eventual fates could be discerned as early as the first
      T lymphocyte division and may have been influenced by asymmetric partitioning of
      the receptor for interleukin 2 (IL-2Ralpha) during mitosis. Our findings
      emphasize the importance of single-cell analyses in understanding fate
      determination and provide new insights into the specification of divergent
      lymphocyte fates early during an immune response to microbial infection. 

PMID- 24584089
TI  - Quantitative proteomics analysis of signalosome dynamics in primary T cells
      identifies the surface receptor CD6 as a Lat adaptor-independent TCR signaling
      hub.
AB  - T cell antigen receptor (TCR)-mediated activation of T cells requires the
      interaction of dozens of proteins. Here we used quantitative mass spectrometry
      and activated primary CD4(+) T cells from mice in which a tag for affinity
      purification was knocked into several genes to determine the composition and
      dynamics of multiprotein complexes that formed around the kinase Zap70 and the
      adaptors Lat and SLP-76. Most of the 112 high-confidence time-resolved protein
      interactions we observed were previously unknown. The surface receptor CD6 was
      able to initiate its own signaling pathway by recruiting SLP-76 and the guanine
      nucleotide-exchange factor Vav1 regardless of the presence of Lat. Our findings
      provide a more complete model of TCR signaling in which CD6 constitutes a
      signaling hub that contributes to the diversification of TCR signaling. 

PMID- 24584090
TI  - The transcription factor BATF operates as an essential differentiation checkpoint
      in early effector CD8+ T cells.
AB  - The transcription factor BATF is required for the differentiation of interleukin
      17 (IL-17)-producing helper T cells (TH17 cells) and follicular helper T cells
      (TFH cells). Here we identified a fundamental role for BATF in regulating the
      differentiation of effector of CD8(+) T cells. BATF-deficient CD8(+) T cells
      showed profound defects in effector population expansion and underwent
      proliferative and metabolic catastrophe early after encountering antigen. BATF,
      together with the transcription factors IRF4 and Jun proteins, bound to and
      promoted early expression of genes encoding lineage-specific transcription
      factors (T-bet and Blimp-1) and cytokine receptors while paradoxically repressing
      genes encoding effector molecules (IFN-gamma and granzyme B). Thus, BATF
      amplifies T cell antigen receptor (TCR)-dependent expression of transcription
      factors and augments the propagation of inflammatory signals but restrains the
      expression of genes encoding effector molecules. This checkpoint prevents
      irreversible commitment to an effector fate until a critical threshold of
      downstream transcriptional activity has been achieved. 

PMID- 24584093
TI  - Existence and consequences of G-quadruplex structures in DNA.
AB  - While the discovery of B-form DNA 60 years ago has defined our molecular view of
      the genetic code, other postulated DNA secondary structures, such as A-DNA, Z
      DNA, H-DNA, cruciform and slipped structures have provoked consideration of DNA
      as a more dynamic structure. Four-stranded G-quadruplex DNA does not use Watson
      Crick base pairing and has been subject of considerable speculation and
      investigation during the past decade, particularly with regard to its potential
      relevance to genome integrity and gene expression. Here, we discuss recent data
      that collectively support the formation of G-quadruplexes in genomic DNA and the
      consequences of formation of this structural motif in biological processes. 

PMID- 24584092
TI  - Supercoiling in DNA and chromatin.
AB  - Supercoiling is a fundamental property of DNA and chromatin. It is modulated by
      polymerase and topoisomerase activities and, through regulated constraint, by
      DNA/chromatin binding proteins. As a non-covalent and elusive topological
      modification, supercoiling has proved intractable to research despite being a
      crucial regulator of nuclear structure and function. Recent studies have improved
      our understanding of the formation, regulation and organisation of supercoiling
      domains in vivo, and reinforce the prospect that the propagation of supercoiling
      can influence local and global chromatin structure. However, to further our
      understanding the development of new experimental tools and models are required
      to better dissect the mechanics of this key topological regulator. 

PMID- 24584091
TI  - Manipulating nuclear architecture.
AB  - The eukaryotic genome is highly organized in the nucleus. Genes can be localized
      to specific nuclear compartments in a manner reflecting their activity. A
      plethora of recent reports has described multiple levels of chromosomal folding
      that can be related to gene-specific expression states. Here we discuss studies
      designed to probe the causal impact of genome organization on gene expression.
      The picture that emerges is that of a reciprocal relationship in which nuclear
      organization is not only shaped by gene expression states but also directly
      influences them. 

PMID- 24584094
TI  - WIP1 and senescence: oxygen matters.

PMID- 24584095
TI  - A complex regulatory network coordinating cell cycles during C. elegans
      development is revealed by a genome-wide RNAi screen.
AB  - The development and homeostasis of multicellular animals requires precise
      coordination of cell division and differentiation. We performed a genome-wide RNA
      interference screen in Caenorhabditis elegans to reveal the components of a
      regulatory network that promotes developmentally programmed cell-cycle
      quiescence. The 107 identified genes are predicted to constitute regulatory
      networks that are conserved among higher animals because almost half of the genes
      are represented by clear human orthologs. Using a series of mutant backgrounds to
      assess their genetic activities, the RNA interference clones displaying similar
      properties were clustered to establish potential regulatory relationships within
      the network. This approach uncovered four distinct genetic pathways controlling
      cell-cycle entry during intestinal organogenesis. The enhanced phenotypes
      observed for animals carrying compound mutations attest to the collaboration
      between distinct mechanisms to ensure strict developmental regulation of cell
      cycles. Moreover, we characterized ubc-25, a gene encoding an E2 ubiquitin
      conjugating enzyme whose human ortholog, UBE2Q2, is deregulated in several
      cancers. Our genetic analyses suggested that ubc-25 acts in a linear pathway with
      cul-1/Cul1, in parallel to pathways employing cki-1/p27 and lin-35/pRb to promote
      cell-cycle quiescence. Further investigation of the potential regulatory
      mechanism demonstrated that ubc-25 activity negatively regulates CYE-1/cyclin E
      protein abundance in vivo. Together, our results show that the ubc-25-mediated
      pathway acts within a complex network that integrates the actions of multiple
      molecular mechanisms to control cell cycles during development. 

PMID- 24584097
TI  - A qualitative assessment of psychosocial impact, coping and adjustment in high
      risk melanoma patients and caregivers.
AB  - The present study qualitatively assessed the psychosocial impacts experienced by
      stage III melanoma patients and caregivers throughout the course of the disease,
      and the coping responses they utilized in an attempt to promote psychosocial
      adjustment. The purpose of the study was to inform the development of a
      supportive care strategy for this population. Nineteen stage III melanoma
      patients and 14 of their caregivers were recruited from the clinical research
      database of the Melanoma Institute Australia. Data were collected using
      semistructured telephone interviews and analysed using thematic analysis.
      Participants reported psychosocial impacts related to diagnosis (shock, panic and
      devastation), treatment (challenges and unsatisfactory care, pain and limitation,
      practical impacts, new roles and responsibilities for the caregiver, caregiver
      inadequacy) and survivorship (ongoing physical problems, watchful waiting,
      feeling abandoned). They also reported global themes relevant to multiple phases
      of the disease (emotional distress, disfigurement, injustice, caregiver
      devaluation). Coping responses were identified related to diagnosis (avoidance),
      treatment (confidence in the treatment team, taking action) and survivorship
      (finding a positive meaning, acceptance and moving on) as well as global themes
      pertaining to multiple disease phases (receiving support, helpful thinking,
      putting on a brave face, redirecting attention, religion). The current findings
      support routine screening for the presence of symptoms and psychological distress
      and appropriate referral when necessary, and for provision of psychosocial
      interventions to provide information and support to stage III melanoma patients
      and caregivers. In addition, provision of communication skills training to all
      health professionals treating melanoma, use of evidence-based strategies for
      improving patient/caregiver understanding and recall, and routine assessment of
      patient-reported outcomes to inform clinical practice would be helpful. 

PMID- 24584096
TI  - CRISPR-Cas systems for editing, regulating and targeting genomes.
AB  - Targeted genome editing using engineered nucleases has rapidly gone from being a
      niche technology to a mainstream method used by many biological researchers. This
      widespread adoption has been largely fueled by the emergence of the clustered,
      regularly interspaced, short palindromic repeat (CRISPR) technology, an important
      new approach for generating RNA-guided nucleases, such as Cas9, with customizable
      specificities. Genome editing mediated by these nucleases has been used to
      rapidly, easily and efficiently modify endogenous genes in a wide variety of
      biomedically important cell types and in organisms that have traditionally been
      challenging to manipulate genetically. Furthermore, a modified version of the
      CRISPR-Cas9 system has been developed to recruit heterologous domains that can
      regulate endogenous gene expression or label specific genomic loci in living
      cells. Although the genome-wide specificities of CRISPR-Cas9 systems remain to be
      fully defined, the power of these systems to perform targeted, highly efficient
      alterations of genome sequence and gene expression will undoubtedly transform
      biological research and spur the development of novel molecular therapeutics for
      human disease. 

PMID- 24584098
TI  - Simulations of dose enhancement for heavy atom nanoparticles irradiated by
      protons.
AB  - A possible dose enhancement effect by proton or electron irradiation in the
      vicinity of nanoparticles consisting of different high Z atomic materials has
      been investigated using the track structure Monte Carlo code TRAX. In the
      simulations, Fe, Ag, Gd, Pt and Au nanoparticles (r = 22 and 2 nm) were
      irradiated with monoenergetic proton beams at energies of therapeutic interest
      (2, 80 and 300 MeV) and 44 keV electrons. Due to the large number of electrons in
      atoms with high atomic numbers, many electrons can be released in Auger cascades
      in addition to the primary ionization process. The potential additional
      nanoscopic radial dose contributions in the presence of metallic nanoparticles
      are assessed by comparison with liquid water and water simulated with the same
      density as the metallic materials. We find a noticeable impact of Auger electrons
      emitted from the nanoparticles. Special focus has been given to the assessment of
      complete sets of low-energy electron cross sections for the nanoparticle
      materials.

PMID- 24584099
TI  - Environmental burden of disease in Europe: assessing nine risk factors in six
      countries.
AB  - BACKGROUND: Environmental health effects vary considerably with regard to their
      severity, type of disease, and duration. Integrated measures of population
      health, such as environmental burden of disease (EBD), are useful for setting
      priorities in environmental health policies and research. This review is a
      summary of the full Environmental Burden of Disease in European countries (EBoDE)
      project report. OBJECTIVES: The EBoDE project was set up to provide assessments
      for nine environmental risk factors relevant in selected European countries
      (Belgium, Finland, France, Germany, Italy, and the Netherlands). METHODS:
      Disability-adjusted life years (DALYs) were estimated for benzene, dioxins,
      secondhand smoke, formaldehyde, lead, traffic noise, ozone, particulate matter
      (PM2.5), and radon, using primarily World Health Organization data on burden of
      disease, (inter)national exposure data, and epidemiological or toxicological risk
      estimates. Results are presented here without discounting or age-weighting.
      RESULTS: About 3-7% of the annual burden of disease in the participating
      countries is associated with the included environmental risk factors. Airborne
      particulate matter (diameter <= 2.5 MUm; PM2.5) is the leading risk factor
      associated with 6,000-10,000 DALYs/year and 1 million people. Secondhand smoke,
      traffic noise (including road, rail, and air traffic noise), and radon had
      overlapping estimate ranges (600-1,200 DALYs/million people). Some of the EBD
      estimates, especially for dioxins and formaldehyde, contain substantial
      uncertainties that could be only partly quantified. However, overall ranking of
      the estimates seems relatively robust. CONCLUSIONS: With current methods and
      data, environmental burden of disease estimates support meaningful policy
      evaluation and resource allocation, including identification of susceptible
      groups and targets for efficient exposure reduction. International exposure
      monitoring standards would enhance data quality and improve comparability.

PMID- 24584100
TI  - Anode-biofilm electron transfer behavior and wastewater treatment under different
      operational modes of bioelectrochemical system.
AB  - Anode-biofilm electron transfer behavior was investigated during the advanced
      wastewater treatment process by three bioelectrochemical systems (BESs):
      microbial fuel cell (MFC), MFC operated under short circuit condition (MSC), and
      microbial electrolysis cell (MEC). Under different operational modes, current
      produced by the anode biofilm varied from 0.92, 4.15 to 8.21mA in the sequence of
      MFC, MSC and MEC, respectively. The cyclic voltammetry test on the anode biofilm
      suggested that the current generation was achieved via various bioelectroactive
      species with formal potentials at -0.473, -0.402 and -0.345V (vs. SCE). Gibbs
      free energy and charge transfer resistance data demonstrated that different
      amounts of available bioelectroactive species functioned in different BESs. The
      comparative investigation among MFC, MSC and MEC suggested that MEC was the only
      feasible operational mode for advanced wastewater treatment, because of its
      superior current generation capability. 

PMID- 24584101
TI  - Dual kinase-bromodomain inhibitors for rationally designed polypharmacology.
AB  - Concomitant inhibition of multiple cancer-driving kinases is an established
      strategy to improve the durability of clinical responses to targeted therapies.
      The difficulty of discovering kinase inhibitors with an appropriate multitarget
      profile has, however, necessitated the application of combination therapies,
      which can pose major clinical development challenges. Epigenetic reader domains
      of the bromodomain family have recently emerged as new targets for cancer
      therapy. Here we report that several clinical kinase inhibitors also inhibit
      bromodomains with therapeutically relevant potencies and are best classified as
      dual kinase-bromodomain inhibitors. Nanomolar activity on BRD4 by BI-2536 and TG
      101348, which are clinical PLK1 and JAK2-FLT3 kinase inhibitors, respectively, is
      particularly noteworthy as these combinations of activities on independent
      oncogenic pathways exemplify a new strategy for rational single-agent
      polypharmacological targeting. Furthermore, structure-activity relationships and
      co-crystal structures identify design features that enable a general platform for
      the rational design of dual kinase-bromodomain inhibitors. 

PMID- 24584102
TI  - A wax ester promotes collective host finding in the nematode Pristionchus
      pacificus.
AB  - Survival of nematode species depends on how successfully they disperse in the
      habitat and find a new host. As a new strategy for collective host finding in the
      nematode Pristionchus pacificus, dauer larvae synthesize an extremely long-chain
      polyunsaturated wax ester (nematoil) that covers the surface of the animal. The
      oily coat promotes congregation of up to one thousand individuals into stable
      'dauer towers' that can reach a beetle host more easily. 

PMID- 24584103
TI  - Ocular coloboma and foetal valproate syndrome: four further cases and a
      hypothesis for aetiology.

PMID- 24584104
TI  - Long-term treatment with tenofovir: prevalence of kidney tubular dysfunction and
      its association with tenofovir plasma concentration.
AB  - BACKGROUND: Monitoring of side effects of long-term HIV treatment has become
      increasingly important. Tenofovir disoproxil fumarate (TDF), a first-line
      treatment option, is associated with kidney tubular dysfunction (KTD). Our
      objective was to further investigate the prevalence and risk factors of KTD, in
      particular its association with TDF plasma concentration in HIV-infected patients
      treated with TDF for at least one year. METHODS: An observational cross-sectional
      single-centre study was conducted. KTD was defined as the presence of at least
      two of the following criteria: urinary alpha1-microglobulin/creatinine ratio >15
      mg/10 mmol; fractional excretion (FE) of phosphate >20% in the presence of
      hypophosphataemia; FE of uric acid >10% in the presence of hypouricaemia and
      glucosuria. Multivariate logistic regression was used to study which variable was
      associated with KTD. RESULTS: A total of 161 HIV patients were included.
      Abnormalities in tubular function were observed in 101 patients (62.7%), while 17
      patients (10.6%) fulfilled the definition of KTD. Urinary alpha1
      microglobulin/creatinine ratio was the most sensitive parameter to detect KTD.
      Multivariate logistic regression showed TDF plasma concentration to be the only
      variable associated with KTD. Post hoc analysis showed a stronger association
      between the product of TDF plasma concentration and TDF exposure and KTD.
      CONCLUSIONS: Parameters of KTD are frequently observed in patients on long-term
      TDF-containing combination antiretroviral therapy. KTD is associated with higher
      TDF plasma concentrations. A stronger association between the product of TDF
      plasma concentration and TDF exposure and KTD could suggest cumulative toxicity.
      A causative role for elevated TDF plasma concentration in development of KTD
      cannot be demonstrated in this cross-sectional analysis. Longitudinal research is
      needed to investigate the development and clinical relevance of KTD.

PMID- 24584105
TI  - Metabolic alterations in HIV-infected pregnant women: moving to metabolic
      tailoring of antiretroviral drugs.
AB  - The most striking effect of increased survival and improved quality of life in
      HIV-infected women undergoing antiretroviral therapy is the feasibility of
      motherhood-desire satisfaction. However, such advantages are often associated
      with drug-related metabolic toxicities, particularly relevant in the pregnancy
      context. Recent guidelines provide recommendations and trends for the use of
      antiretroviral therapy in pregnant women, but current literature falls short of
      providing specific insights on the need for metabolic monitoring and treatment in
      HIV-infected pregnant women. In this review we provide specific insight into the
      state-of-the-art of: detection, evaluation, and management of metabolic
      alterations in this special population. Pregnancy is in fact a metabolic
      transition process, potentially associated with specific diseases in the mother,
      in the newborn, and in the adulthood of the child. We will not simply discuss
      antiretroviral therapy metabolic toxicities, but rather their interaction with
      the physiological metabolic changes occurring during pregnancy. Close monitoring
      is needed to diagnose metabolic alterations that can lead to adverse outcomes in
      the mother, in the newborn, and potentially in adulthood. Lifestyle interventions
      and an appropriate metabolic tailoring of antiretroviral therapy drugs need to be
      considered in the prevention and treatment of metabolic alteration during
      pregnancy.

PMID- 24584107
TI  - Stribild(r) (elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil
      fumarate): a new paradigm for HIV-1 treatment.
AB  - Stribild(r) (elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate)
      is a new single-tablet, fixed-dose formulation approved by both the US Food and
      Drug Administration and the European Medicine Agency as antiretroviral therapy.
      It is the first once-a-day therapy option containing an integrase inhibitor and
      cobicistat, a novel pharmacokinetic boosting agent without activity on HIV.
      Stribild(r) has demonstrated non-inferior virological efficacy and a similar
      recovery of CD4+ T-cells when compared to Atripla(r)
      (efavirenz/emtricitabine/tenofovir) and to ritonavir-boosted atazanavir plus
      emtricitabine/tenofovir in two large, phase III randomized clinical trials at 48,
      96, and 144 weeks. These results are consistent in all CD4+ and HIV RNA strata.
      Although well-tolerated, self-limiting nausea has been reported in more than 10%
      of patients in both trials. Cobicistat has clinically significant drug-drug
      interactions with drugs that are metabolized by the cytochrome P450 3A4 subfamily
      enzymes, and causes a minimal reversible decrease of the estimated glomerular
      filtration rate due to inhibition of molecular transporters of creatinine in
      kidney tubules. Elvitegravir primary resistance mutations associated with
      treatment failure often lead to cross-resistance to raltegravir.

PMID- 24584106
TI  - Origin and diversity of human retroviruses.
AB  - Simian immunodeficiency viruses, simian T-cell lymphotropic viruses, and simian
      foamy viruses from nonhuman primates have crossed the species barrier to humans
      at several time points, leading to the HIV and human T lymphotropic virus
      epidemic and to sporadic cases of human infections with simian foamy viruses,
      respectively. Efficient infection and spread in humans differs between simian
      foamy virus, simian lymphotropic virus, and simian immunodeficiency virus, but
      seems also to differ among the different viruses from the same simian lineage, as
      illustrated by the different spread of HIV-1 M, N O, P or for the different HIV-2
      groups. Among the four HIV-1 groups, only HIV-1 group M has spread worldwide, and
      the actual diversity within HIV-1 M (subtypes, circulating recombinants) is the
      result of subsequent evolution and spread in the human population. HIV-2 only
      spread to some extent in West Africa, and similarly as for HIV-1, the nine HIV-2
      groups have also a different epidemic history. Four types of human T lymphotropic
      virus, type 1 to 4, have been described in humans and for three of them simian
      counterparts (simian T lymphotropic virus-1, -2, -3) have been identified in
      multiple nonhuman primate species. The majority of human infections are with
      human T lymphotropic virus-1, which is present throughout the world as clusters
      of high endemicity. Humans are susceptible to a wide variety of simian foamy
      viruses and seem to acquire these viruses more readily than simian
      immunodeficiency viruses or simian T lymphotropic viruses, but neither signs of
      disease in humans nor human-to-human transmission of simian foamy virus have been
      documented yet. The current HIV-1 M epidemic illustrates the impact of a single
      cross-species transmission. The recent discovery of HIV-1 P, HIV-2 I, new human T
      lymphotropic virus-1 and -3 variants, as well as simian foamy virus infections in
      humans in Central Africa, show that our knowledge of genetic diversity and cross
      species transmissions of simian retroviruses is still incomplete.

PMID- 24584108
TI  - A comparison of donor and control group quality of life.
AB  - BACKGROUND: Informed consent of prospective donors should include information
      about the quality of life (QoL) of existing donors, especially those within the
      relevant country. This study aimed to provide information on Malaysian organ
      donors' QoL relative to a control group. MATERIAL/METHODS: Using a shorter
      version of the SF-36, QoL of 80 donors from the University of Malaya Medical
      Center (UMMC), Malaysia was surveyed and compared to QoL of 80 selected healthy
      individuals. ANOVA and General Linear Model (GLM) procedure were each applied for
      the QoL comparison, which was based on gender and age. RESULTS: Donors recorded a
      better QoL relative to the control group. Comparison across gender revealed that
      differences are more obvious for males than females. Donor/control comparison
      across age groups reveals that donors aged 56 and above reported significantly
      better QoL in most domains relative to other age groups. CONCLUSIONS: Information
      on donor QoL should be made available to the public to present a comprehensive
      picture of the consequences of organ donation. Nonetheless, we also argue that,
      despite the merits of organ donation, caution is required before concluding that
      donors have better QoL because the present research outcomes may reflect a self
      selection bias in which respondents only included donors engaging in regular
      follow-ups.

PMID- 24584116
TI  - Epigallocatechin-3-gallate restores the Bcl-2 expression in liver of young rats
      challenged with hypercholesterolemia but not in aged rats: an insight into its
      disparity of efficacy on advancing age.
AB  - Advanced age significantly increases cholesterol levels, however, when combined
      with a high cholesterol diet it not only leads to life-threatening conditions
      like atherosclerosis, but also plays a central role in the pathogenesis of
      hepatic damage and its complications. Even though extensive studies have been
      carried out to elucidate the causative factors that lead to hepatic steatosis
      associated with liver damage in young rats due to hypercholesterolemia, events
      that occur in aged rats where a different milieu is presented by up and down
      regulation of various genes co-existing, has not been extensively studied. Hence,
      this study comparatively evaluates the impact of hypercholesterolemic stress
      induced liver damage in young and aged rats and the efficacy of epigallocatechin
      3-gallate to protect the liver in both young and aged rats with special reference
      to apoptosis. Moreover, the work has been designed to investigate whether aged
      rats act as better models for studying the efficacy of atheroprotective drugs.
      Male albino rats of the Wistar strain were used in this study. Basic biochemical
      assays along with apoptotic markers assayed in the current study revealed that
      treatment with EGCG significantly reverted the alterations in both biochemical
      and histological parameters in young and aged hypercholesterolemic rats when
      compared to their respective controls. However, the extent of reversion was far
      superior in young rats, when compared to aged rats. EGCG reduced hepatic Bax
      expression in both young and aged hypercholesterolemic rats. On the other hand,
      Bcl-2 expression was up regulated significantly in young hypercholesterolemic
      rats, but not in aged hypercholesterolemic rats on treatment with EGCG. This
      throws light on the efficacy of the treatment differing in young and aged rats as
      well; atheroprotective drugs shall be tested for their efficacy in aged
      hypercholesterolemic models. 

PMID- 24584117
TI  - MicroRNA-126-5p promotes endothelial proliferation and limits atherosclerosis by
      suppressing Dlk1.
AB  - Atherosclerosis, a hyperlipidemia-induced chronic inflammatory process of the
      arterial wall, develops preferentially at sites where disturbed laminar flow
      compromises endothelial cell (EC) function. Here we show that endothelial miR-126
      5p maintains a proliferative reserve in ECs through suppression of the Notch1
      inhibitor delta-like 1 homolog (Dlk1) and thereby prevents atherosclerotic lesion
      formation. Endothelial recovery after denudation was impaired in Mir126(-/-) mice
      because lack of miR-126-5p, but not miR-126-3p, reduced EC proliferation by
      derepressing Dlk1. At nonpredilection sites, high miR-126-5p levels in
      endothelial cells confer a proliferative reserve that compensates for the
      antiproliferative effects of hyperlipidemia, such that atherosclerosis was
      exacerbated in Mir126(-/-) mice. In contrast, downregulation of miR-126-5p by
      disturbed flow abrogated EC proliferation at predilection sites in response to
      hyperlipidemic stress through upregulation of Dlk1 expression. Administration of
      miR-126-5p rescued EC proliferation at predilection sites and limited
      atherosclerosis, introducing a potential therapeutic approach. 

PMID- 24584118
TI  - Netrin-1 promotes adipose tissue macrophage retention and insulin resistance in
      obesity.
AB  - During obesity, macrophage accumulation in adipose tissue propagates the chronic
      inflammation and insulin resistance associated with type 2 diabetes. The factors,
      however, that regulate the accrual of macrophages in adipose tissue are not well
      understood. Here we show that the neuroimmune guidance cue netrin-1 is highly
      expressed in obese but not lean adipose tissue of humans and mice, where it
      directs the retention of macrophages. Netrin-1, whose expression is induced in
      macrophages by the saturated fatty acid palmitate, acts via its receptor Unc5b to
      block their migration. In a mouse model of diet-induced obesity, we show that
      adipose tissue macrophages exhibit reduced migratory capacity, which can be
      restored by blocking netrin-1. Furthermore, hematopoietic deletion of Ntn1
      facilitates adipose tissue macrophage emigration, reduces inflammation and
      improves insulin sensitivity. Collectively, these findings identify netrin-1 as a
      macrophage retention signal in adipose tissue during obesity that promotes
      chronic inflammation and insulin resistance. 

PMID- 24584120
TI  - A novel high-throughput irradiator for in vitro radiation sensitivity bioassays.
AB  - This paper describes the development and characterization of a fully automated in
      vitro cell irradiator using an electronic brachytherapy source to perform
      radiation sensitivity bioassays. This novel irradiator allows complex variable
      dose and dose rate schemes to be delivered to multiple wells of 96-well culture
      plates used in standard biological assays. The Xoft Axxent(r) eBxTM was chosen as
      the x-ray source due to its ability to vary tube current up to 300 uA for a 50
      kVp spectrum using clinical surface applicators. Translation of the multiwell
      plate across the fixed radiation field is achieved using a precision motor driven
      computer controlled positioning system. A series of measurements was performed to
      characterize dosimetric performance of the system. Measurements have shown that
      the radiation output measured with an end window ionization chamber is stable
      between operating currents of 50-300 uA. In addition, radiochromic film was used
      to characterize the field flatness and symmetry. The average field flatness in
      the in-plane and cross-plane direction was 2.9 +/- 1.0% and 4.0 +/- 1.7%,
      respectively. The average symmetry in the in-plane and cross-plane direction was
      1.8 +/- 0.9% and 1.6 +/- 0.5%, respectively. The optimal focal spot resolution at
      the cellular plane was determined by measuring sequential irradiations on
      radiochromic film for three different well spacing schemes. It was determined
      that the current system can irradiate every other well with negligible impact on
      the radiation field characteristics. Finally, a performance comparison between
      this system and a common cabinet irradiator is presented.

PMID- 24584121
TI  - Regional distribution of anchorless prion protein, PrP226*, in the human brain.
AB  - It was shown previously that truncated molecules of prion protein can be found in
      brains of patients with some types of transmissible spongiform encephalopathy.
      One such molecule, PrP226*, is a fragment of prion protein, truncated at Tyr226.
      It was found to be present in aggregates, from which it can be released using
      chaotropic salts. In this study we investigated the distribution of PrP226* in
      Creutzfeldt-Jakob disease affected human brain, employing the mAb V5B2,
      specifically recognizing this fragment. The results show that PrP226* is not
      evenly distributed among different regions of human brain. Among brain regions
      analyzed, the fragment was found most likely to be accumulated in the cerebellum.
      Its distribution correlates with the distribution of PrP(Sc). 

PMID- 24584119
TI  - Multiplexed ion beam imaging of human breast tumors.
AB  - Immunohistochemistry (IHC) is a tool for visualizing protein expression that is
      employed as part of the diagnostic workup for the majority of solid tissue
      malignancies. Existing IHC methods use antibodies tagged with fluorophores or
      enzyme reporters that generate colored pigments. Because these reporters exhibit
      spectral and spatial overlap when used simultaneously, multiplexed IHC is not
      routinely used in clinical settings. We have developed a method that uses
      secondary ion mass spectrometry to image antibodies tagged with isotopically pure
      elemental metal reporters. Multiplexed ion beam imaging (MIBI) is capable of
      analyzing up to 100 targets simultaneously over a five-log dynamic range. Here,
      we used MIBI to analyze formalin-fixed, paraffin-embedded human breast tumor
      tissue sections stained with ten labels simultaneously. The resulting data
      suggest that MIBI can provide new insights into disease pathogenesis that will be
      valuable for basic research, drug discovery and clinical diagnostics. 

PMID- 24584132
TI  - A structural model for glutathione-complexed iron-sulfur cluster as a substrate
      for ABCB7-type transporters.
AB  - Glutathione-complexed [2Fe-2S] cluster is shown to significantly stimulate the
      ATPase activity of an ABCB7-type transporter in both solution and proteoliposome
      bound forms (KD ~ 68 MUM). The cluster is a likely natural substrate for this
      transporter, which has been implicated in cytosolic Fe-S cluster protein
      maturation. A possible substrate-binding site is identified on a new structural
      model for the active transporter. 

PMID- 24584133
TI  - Palladium-catalyzed aerobic oxidative coupling of enantioenriched primary allylic
      amines with sulfonyl hydrazides leading to optically active allylic sulfones.
AB  - A range of highly enantioenriched primary allylic amines underwent palladium
      catalyzed oxidative coupling with sulfonyl hydrazides open to air at room
      temperature to give structurally diverse allylic sulfones in moderate to
      excellent yields with excellent retention of ee. 

PMID- 24584134
TI  - Assessing safety and immunogenicity of post-exposure prophylaxis following
      interchangeability of rabies vaccines in humans.
AB  - Rabies post exposure prophylaxis with cell culture vaccines by either
      intramuscular route or intradermal route spans over a period of one month. World
      Health Organization recommends completing post exposure prophylaxis against
      rabies with the same cell culture or embryonated egg rabies vaccine and with same
      route of administration and any deviation from this shall be an exception. In the
      present study, the safety and immunogenicity of rabies post-exposure prophylaxis
      was studied prospectively in 90 animal bite cases that had interchangeability of
      rabies vaccines either by route of administration or brand/type and such changes
      had occurred due to logistical/financial problems. Among them, 47 had change in
      route of administration from intramuscular to intradermal or vice versa and 43
      had change in the brand/type of cell culture rabies vaccine. All of them had
      category III rabies exposure and received equine rabies immunoglobulin along with
      the rabies vaccine. None of the study subjects had any adverse reactions. The
      rabies virus neutralizing antibody titers was assessed by rapid fluorescent focus
      inhibition test and all the vaccinees had titers >=0.5 IU per mL on day 14 which
      is considered as adequate for protection against rabies. Thus, the present study
      showed that, rabies post-exposure prophylaxis was safe and immunogenic despite
      changes in the route of administration and brand/type of rabies vaccine. 

PMID- 24584135
TI  - Epilepsy surgery for glioneuronal tumors in childhood: avoid loss of time.
AB  - BACKGROUND: In contrast to the abundance of seizure outcome reports in epilepsy
      surgery for glioneuronal tumors in childhood and adolescence, there is a dearth
      of information regarding cognitive outcomes. OBJECTIVE: To investigate the
      seizure and cognitive outcome of children and adolescents that underwent
      resective surgery for glioneuronal tumor-associated refractory epilepsy and
      determine their predictive factors. METHODS: We retrospectively analyzed the
      presurgical findings, resection types, and outcomes over 1.3 to 12.3 years (mean,
      7.3) of 29 consecutive patients, who underwent resection in 2000 to 2011. The
      mean age at epilepsy onset was 7.9 years (range, 0-15.4), the mean age at surgery
      was 11.7 years (range, 2.6-17.3), and the mean epilepsy duration to surgery was
      3.8 years (range, 0.3-15.3). Etiology comprised 13 dysembryoplastic
      neuroepithelial tumors and 16 gangliogliomas, with additional focal cortical
      dysplasia in 5 cases. RESULTS: Eighty-six percent of children were seizure free
      12 months after surgery; at final follow-up, 76% remained seizure free and 62%
      had discontinued antiepileptic drugs. Gross total resection was related to
      significantly higher rates of seizure freedom. Higher presurgical cognitive
      functioning (full-scale IQ, verbal IQ) was related to shorter epilepsy duration
      to surgery independent of age at epilepsy onset, thus determining postsurgical
      functioning. Improvements in verbal IQ, performance IQ, and visual memory as well
      as a trend toward improvement in full-scale IQ were established after surgery.
      Despite individual losses in full-scale IQ, verbal or visual memory, no
      deterioration was noted in any cognitive variable on a group level. CONCLUSION:
      Completeness of resection predisposes to favorable outcomes regarding seizure
      alleviation. Whereas cognitive functioning deteriorates with time in glioneuronal
      tumor-related refractory epilepsy, surgery is linked to improvement rather than
      to deterioration on a group level.

PMID- 24584137
TI  - Contrast-enhanced angiographic computed tomography for detection of aneurysm
      remnants after clipping: a comparison with digital subtraction angiography in 112
      clipped aneurysms.
AB  - BACKGROUND: For preclusion of remnants after aneurysm clipping, a reliable,
      noninvasive imaging technique is desirable. OBJECTIVE: To evaluate the
      reliability of optimized angiographic computed tomography with intravenous
      contrast agent injection (ivACT) in detecting remnants after aneurysmal clipping
      compared with digital subtraction angiography (DSA), the gold standard. METHODS:
      We included 84 patients with 112 clipped cerebral aneurysms of the anterior
      circulation. For treatment, 116 clips of cobalt and 57 clips of titanium alloy
      were used. In each patient, we performed an ivACT with dual rotational
      acquisition and a DSA. Data from ivACT were postprocessed with a dual-volume
      technique with newly implemented reconstructions modes. Aneurysm remnants were
      measured, classified, and correlated with DSA by 2 raters. RESULTS: In total, 12
      remnants were revealed by DSA, meaning a prevalence of 11%. IvACT demonstrated a
      sensitivity of 75% to 92% and a specificity of 99% in detecting remnants up to a
      minimal size of 0.7 * 0.3 mm. Classification of remnants by ivACT was identical
      to that by DSA, and assessment of size showed a significant correlation with DSA
      (P < .001). No significant differences between cobalt and titanium alloy were
      revealed concerning artifacts. CONCLUSION: Optimized ivACT with enhanced
      postprocessing demonstrated high sensitivity and specificity in detecting
      remnants after aneurysm clipping in the anterior circulation. Classification and
      assessment of remnant size and detection of relevant parent artery stenosis
      showed high accuracy of ivACT compared with DSA. Our results indicate that ivACT
      might become a noninvasive alternative to DSA for postsurgical control.

PMID- 24584136
TI  - Use of cone-beam computed tomography angiography in planning for gamma knife
      radiosurgery for arteriovenous malformations: a case series and early report.
AB  - BACKGROUND: The effectiveness of Gamma Knife radiosurgery (GKR) for cerebral
      arteriovenous malformations (AVMs) is predicated on inclusion of the entire nidus
      while excluding normal tissue. As such, GKR may be limited by the resolution and
      accuracy of the imaging modality used in targeting. OBJECTIVE: We present the
      first case series to demonstrate the feasibility of using ultrahigh-resolution C
      arm cone-beam computed tomography angiography (CBCT-A) in AVM targeting. METHODS:
      From June 2009 to June 2013, CBCT-A was used for targeting of all patients with
      AVMs treated with GKR at our institution. Patients underwent Leksell stereotactic
      head frame placement followed by catheter-based biplane 2-dimensional digital
      subtraction angiography, 3-dimensional rotational angiography, as well as CBCT-A.
      The CBCT-A dataset was used for stereotactic planning for GKR. Patients were
      followed at 1, 3, 6, and 12 months and then annually thereafter. RESULTS: CBCT-A
      based targeting was used in 22 consecutive patients. CBCT-A provided detailed
      spatial resolution and sensitivity of nidal angioarchitecture enabling treatment.
      The average radiation dose to the margin of the AVM nidus corresponding to the
      50% isodose line was 15.6 Gy. No patient had treatment-associated hemorrhage. At
      early follow-up (mean, 16 months), 84% of patients had a decreasing or
      obliterated AVM nidus. CONCLUSION: CBCT-A-guided radiosurgery is feasible and
      useful because it provides sufficient detailed resolution and sensitivity for
      imaging brain AVMs.

PMID- 24584138
TI  - Magnetic resonance-guided laser ablation improves local control for
      postradiosurgery recurrence and/or radiation necrosis.
AB  - BACKGROUND: Enhancing lesions that progress after stereotactic radiosurgery are
      often tumor recurrence or radiation necrosis. Magnetic resonance-guided laser
      induced thermal therapy (LITT) is currently being explored for minimally invasive
      treatment of intracranial neoplasms. OBJECTIVE: To report the largest series to
      date of local control with LITT for the treatment of recurrent enhancing lesions
      after stereotactic radiosurgery for brain metastases. METHODS: Patients with
      recurrent metastatic intracranial tumors or radiation necrosis who had previously
      undergone radiosurgery and had a Karnofsky performance status of >70 were
      eligible for LITT. Sixteen patients underwent a total of 17 procedures. The
      primary end point was local control using magnetic resonance imaging scans at
      intervals of >4 weeks. Radiographic outcomes were followed up prospectively until
      death or local recurrence (defined as >25% increase in volume compared with the
      24-hour postprocedural scan). RESULTS: Fifteen patients (age, 46-82 years) were
      available for follow-up. Primary tumor histology was non-small-cell lung cancer
      (n = 12) and adenocarcinoma (n = 3). On average, the lesion size measured 3.66 cm
      (range, 0.46-25.45 cm); there were 3.3 ablations per treatment (range, 2-6), with
      7.73-cm depth to target (range, 5.5-14.1 cm), ablation dose of 9.85 W (range, 8.2
      12.0 W), and total ablation time of 7.43 minutes (range, 2-15 minutes). At a
      median follow-up of 24 weeks (range, 4-84 weeks), local control was 75.8% (13 of
      15 lesions), median progression-free survival was 37 weeks, and overall survival
      was 57% (8 of 14 patients). Two patients experience recurrence at 6 and 18 weeks
      after the procedure. Five patients died of extracranial disease progression; 1
      patient died of neurological progression elsewhere in the brain. CONCLUSION:
      Magnetic resonance imaging-guided LITT is a well-tolerated procedure and may be
      effective in treating tumor recurrence/radiation necrosis.

PMID- 24584139
TI  - Intraobserver and interobserver agreement in visual inspection for xanthochromia:
      implications for subarachnoid hemorrhage diagnosis, computed tomography
      validation studies, and the Walton rule: methodological mistake.

PMID- 24584140
TI  - In reply: intraobserver and interobserver agreement in visual inspection for
      xanthochromia: implications for subarachnoid hemorrhage diagnosis, computed
      tomography validation studies, and the walton rule: methodological mistake.

PMID- 24584141
TI  - Chondroitin 6-O-sulfate ameliorates experimental autoimmune encephalomyelitis.
AB  - Chondroitin sulfate proteoglycans (CSPGs) are the main component of the
      extracellular matrix in the central nervous system (CNS) and influence
      neuroplasticity. Although CSPG is considered an inhibitory factor for nerve
      repair in spinal cord injury, it is unclear whether CSPG influences the
      pathogenetic mechanisms of neuroimmunological diseases. We induced experimental
      autoimmune encephalomyelitis (EAE) in chondroitin 6-O-sulfate transferase 1
      deficient (C6st1(-/-)) mice. C6ST1 is the enzyme that transfers sulfate residues
      to position 6 of N-acetylgalactosamine in the sugar chain of CSPG. The phenotypes
      of EAE in C6st1(-/-) mice were more severe than those in wild-type (WT) mice
      were. In adoptive-transfer EAE, in which antigen-reactive T cells from WT mice
      were transferred to C6st1(-/-) and WT mice, phenotypes were significantly more
      severe in C6st1(-/-) than in WT mice. The recall response of antigen-reactive T
      cells was not significantly different among the groups. Furthermore, the number
      of pathogenic T cells within the CNS was also not considerably different. When
      EAE was induced in C6ST1 transgenic mice with C6ST1 overexpression, the mice
      showed considerably milder symptoms compared with those in WT mice. In
      conclusion, the presence of sulfate at position 6 of N-acetylgalactosamine of
      CSPG may influence the effecter phase of EAE to prevent the progression of
      pathogenesis. Thus, modification of the carbohydrate residue of CSPG may be a
      novel therapeutic strategy for neuroimmunological diseases such as multiple
      sclerosis. 

PMID- 24584142
TI  - Downregulation of microRNA-431 by human interferon-beta inhibits viability of
      medulloblastoma and glioblastoma cells via upregulation of SOCS6.
AB  - miRNAs are small non-coding RNAs that inhibit gene expression by cleaving or
      hindering the translation of target mRNAs. In this study, we focused on miR-431,
      which mediated inhibition of cell viability by human interferon-beta (HuIFN
      beta). We aimed to demonstrate an antineoplastic effect of HuIFN-beta via miR-431
      expression against medulloblastoma and glioblastoma, because HuIFN-beta is
      frequently used in adjuvant therapy of these tumors. Addition of HuIFN-beta to
      medulloblastoma and glioblastoma cells reduced viability, significantly decreased
      miR-431 expression, upregulated expression of SOCS6 (putative miR-431 target
      genes) and inhibited Janus kinase (JAK) 1 and signal transducer and activator of
      transcription (STAT) 2. The mitogen-activated protein kinase (MAPK) pathway, but
      not the phosphoinositide 3-kinase (PI3K)-Akt pathway, was downregulated in
      medulloblastoma cells, whereas the PI3K-Akt pathway, but not the MAPK pathway,
      was downregulated in glioblastoma cells. Addition of HuIFN-beta and transient
      transfection with miR-431 to medulloblastoma and glioblastoma cells did not
      reduce viability, downregulated expression of SOCS6, and concomitantly activated
      the JAK1 and STAT2. We propose that, in medulloblastoma and glioblastoma cells,
      HuIFN-beta decreases miR-431 expression and upregulates SOCS6 expression, and
      consequently inhibit cell proliferation by suppressing the JAK-STAT signaling
      pathway. 

PMID- 24584155
TI  - Numerical simulation of X-wing type biplane flapping wings in 3D using the
      immersed boundary method.
AB  - The numerical simulation of an insect-sized 'X-wing' type biplane flapping wing
      configuration is performed in 3D using an immersed boundary method solver at
      Reynolds numbers equal to 1000 (1 k) and 5 k, based on the wing's root chord
      length. This X-wing type flapping configuration draws its inspiration from
      Delfly, a bio-inspired ornithopter MAV which has two pairs of wings flapping in
      anti-phase in a biplane configuration. The objective of the present investigation
      is to assess the aerodynamic performance when the original Delfly flapping wing
      micro-aerial vehicle (FMAV) is reduced to the size of an insect. Results show
      that the X-wing configuration gives more than twice the average thrust compared
      with only flapping the upper pair of wings of the X-wing. However, the X-wing's
      average thrust is only 40% that of the upper wing flapping at twice the stroke
      angle. Despite this, the increased stability which results from the smaller lift
      and moment variation of the X-wing configuration makes it more suited for sharp
      image capture and recognition. These advantages make the X-wing configuration an
      attractive alternative design for insect-sized FMAVS compared to the single wing
      configuration. In the Reynolds number comparison, the vorticity iso-surface plot
      at a Reynolds number of 5 k revealed smaller, finer vortical structures compared
      to the simulation at 1 k, due to vortices' breakup. In comparison, the force
      output difference is much smaller between Re = 1 k and 5 k. Increasing the body
      inclination angle generates a uniform leading edge vortex instead of a conical
      one along the wingspan, giving higher lift. Understanding the force variation as
      the body inclination angle increases will allow FMAV designers to optimize the
      thrust and lift ratio for higher efficiency under different operational
      requirements. Lastly, increasing the spanwise flexibility of the wings increases
      the thrust slightly but decreases the efficiency. The thrust result is similar to
      one of the spanwise studies, but the efficiency result contradicts it, indicating
      that other flapping parameters are involved as well. Results from this study
      provide a deeper understanding of the underlying aerodynamics of the X-wing type,
      which will help to improve the performance of insect-sized FMAVs using this
      unique configuration. 

PMID- 24584156
TI  - Diverse in vitro and in vivo anti-inflammatory effects of trichlorido-gold(III)
      complexes with N6-benzyladenine derivatives.
AB  - A series of gold(III) complexes involving differently substituted derivatives of
      a plant hormone N6-benzyladenine (HL1-5) is reported. The complexes have the
      general formula [Au(HL1-5)Cl3]?nH2O (n=0 for 1, 3-5; and n=1 for 2), where N6-(2
      fluorobenzyl)adenine (HL1), N6-(2-chlorobenzyl)adenine (HL2), N6-(3
      chlorobenzyl)adenine (HL3), N6-(4-chlorobenzyl)adenine (HL4) and N6-(4
      methylbenzyl)adenine (HL5) represent the N9-coordinated ligands. The results of
      thorough characterization (elemental and thermal analyses, FT-IR, Raman and NMR
      spectroscopies, ESI+ mass spectrometry, conductivity measurements, DFT
      calculations) showed that the presented complexes 1-5 involve a central gold(III)
      atom coordinated in a square-planar geometry by the N9 atom of the purine moiety
      of HL1-5 and by three chlorido ligands. The complexes (1-5) were studied in vitro
      for cytotoxicity and anti-inflammatory activity on LPS-activated macrophages (THP
      1 cell line), and in vivo for anti-inflammatory effects (1, 2, 5) using the
      carrageenan-induced hind paw oedema model on rats. Surprisingly, the results on
      the in vitro level revealed that the complexes show negligible cytotoxicity and
      anti-inflammatory activity, however, the activity on the in vivo level was found
      to be significant, fully comparable with the utilized drug Indomethacin, or even
      better as compared to a gold-containing metallodrug Auranofin. 

PMID- 24584166
TI  - Accumulation of heavy metals in different body tissues of Atlantic salmon, Salmo
      salar L., exposed to a model mixture (Cu, Zn, Ni, Cr, Pb, Cd) and singly to
      nickel, chromium, and lead.
AB  - One-year-old Atlantic salmon smolts were exposed for 2 weeks either to six
      priority heavy metal mixture or to Ni, Pb, and Cr singly at a concentration
      corresponding to Lithuanian inland water standards: Cu - 0.01, Zn - 0.1, Ni -
      0.01, Cr - 0.01, Cd - 0.005 and Pb - 0.005 mg/L, respectively under semi-static
      conditions. The presence of metal mixture in the water only partly (by 50 %)
      affected the accumulation of single metals in body tissues (muscle, gills, liver
      and kidneys) probably due to the synergistic interactions among metals. Although
      metal concentrations increased in most cases, only Pb exceeded recommended level
      for human consumption (0.2 Pb mg/L) by 1.1-fold to 2.1-fold.

PMID- 24584167
TI  - Allergic rhinitis: Diagnosis through management.
AB  - Allergic rhinitis (AR) is an immune hypersensitivity response of the nasal mucosa
      affecting children and adults. Patients with a genetic predisposition become
      sensitized to certain allergens over time with repeated exposures. This article
      will discuss AR from diagnosis through treatment.

PMID- 24584168
TI  - The importance of the history and physical in diagnosis.
AB  - This article supports the importance of using the patient history and physical as
      a basis for selecting relevant diagnostic testing, which leads to a timely and
      accurate diagnosis. This process protects patients from the risks of unnecessary
      testing and is cost-effective.

PMID- 24584154
TI  - Identification of autophagy as a longevity-assurance mechanism in the aging model
      Podospora anserina.
AB  - The filamentous ascomycete Podospora anserina is a well-established aging model
      in which a variety of different pathways, including those involved in the control
      of respiration, ROS generation and scavenging, DNA maintenance, proteostasis,
      mitochondrial dynamics, and programmed cell death have previously been
      demonstrated to affect aging and life span. Here we address a potential role of
      autophagy. We provide data demonstrating high basal autophagy levels even in
      strains cultivated under noninduced conditions. By monitoring an N-terminal
      fusion of EGFP to the fungal LC3 homolog PaATG8 over the lifetime of the fungus
      on medium with and without nitrogen supplementation, respectively, we identified
      a significant increase of GFP puncta in older and in nitrogen-starved cultures
      suggesting an induction of autophagy during aging. This conclusion is supported
      by the demonstration of an age-related and autophagy-dependent degradation of a
      PaSOD1-GFP reporter protein. The deletion of Paatg1, which leads to the lack of
      the PaATG1 serine/threonine kinase active in early stages of autophagy induction,
      impairs ascospore germination and development and shortens life span. Under
      nitrogen-depleted conditions, life span of the wild type is increased almost 4
      fold. In contrast, this effect is annihilated in the Paatg1 deletion strain,
      suggesting that the ability to induce autophagy is beneficial for this fungus.
      Collectively, our data identify autophagy as a longevity-assurance mechanism in
      P. anserina and as another surveillance pathway in the complex network of
      pathways affecting aging and development. These findings provide perspectives for
      the elucidation of the mechanisms involved in the regulation of individual
      pathways and their interactions.

PMID- 24584169
TI  - Case-based discussion from the Royal Devon and Exeter NHS Foundation Trust: a
      painful paradox.

PMID- 24584170
TI  - Update in intensive care medicine: acute liver failure. Initial management,
      supportive treatment and who to transplant.
AB  - PURPOSE OF REVIEW: Acute liver failure (ALF) is associated with significant
      mortality. Although specific therapies may be available, the evidence base for
      these and for many aspects of supportive therapy has been slow to emerge. Liver
      transplantation continues to be a cornerstone of treatment, and the management of
      ALF, therefore, remains the domain of the specialist ICU. The purpose of this
      review is to identify and critically appraise the recent evidence and to inspire
      those who strive to provide excellent care for a difficult patient cohort. RECENT
      FINDINGS: Effective vaccination programmes have reduced the incidence of viral
      hepatitis in Europe and the USA. Spontaneous survival has improved in causes such
      as acetaminophen toxicity. Early recognition and proactive intensive management
      have reduced the incidence of early neurological death. The use of artificial
      liver assist devices and therapeutic plasma exchange is controversial, yet
      intriguing, with some early evidence of efficacy. SUMMARY: Increasingly
      sophisticated prognostication tools are evolving, which have the potential to
      transform clinical decision-making. A review of the indications for
      transplantation in acetaminophen toxicity is overdue. The use of therapeutic
      plasma exchange and extracorporeal liver support in ALF requires further
      investigation.

PMID- 24584171
TI  - Intracranial pressure after the BEST TRIP trial: a call for more monitoring.
AB  - PURPOSE OF REVIEW: Increased intracranial pressure (ICP) is associated with worse
      outcome after traumatic brain injury (TBI), but whether its management improves
      the outcome is unclear. In this review, we will examine the implications of the
      Benchmark Evidence from South American Trials: Treatment of Intracranial Pressure
      (BEST TRIP) trial, evidence for an influence of ICP care on outcome, and a need
      for greater understanding of the pathophysiology than just ICP through multimodal
      monitoring (MMM) to enhance the outcome. RECENT FINDINGS: The primary impact of
      the BEST TRIP trial, a randomized clinical trial that examined two TBI management
      strategies, one that used an ICP monitor, is in research and should not alter
      clinical practice. Analyses of large databases suggest TBI care based on the
      Brain Trauma Foundation guidelines and management of intracranial hypertension
      can improve patient outcome. However, accumulating evidence demonstrates there
      are several mechanisms of secondary brain injury (SBI), for example,
      microvascular dysfunction or alterations in glucose utilization that cannot be
      detected using an ICP monitor. In these patients, growing clinical evidence
      suggests that MMM can help manage SBI and improve TBI outcome. SUMMARY: ICP-based
      monitoring and treatment alone may not be enough to enhance TBI outcome, but ICP
      and cerebral perfusion pressure therapy remain important in TBI care. Although
      high-quality evidence for MMM is limited, it should be more widely adapted to
      better understand the complex pathophysiology after TBI, better target care, and
      identify new therapeutic opportunities.

PMID- 24584172
TI  - Association between suicidal ideation and behavior, and depression, anxiety, and
      perceived social support in cancer patients.
AB  - BACKGROUND: The aim of this study was to determine the relationship between
      suicidal behavior and associated factors such as depression, anxiety, and
      perceived social support level in cancer patients. MATERIAL AND METHODS: The
      study group included 102 patients who were under treatment in the oncology
      department and the control group included 100 individuals with similar
      sociodemographic features. A sociodemographic information form, Beck depression
      inventory, Beck anxiety inventory, suicidal behavior inventory, suicidal ideation
      inventory, and multidimensional inventory of perceived social support were used.
      RESULTS: The mean Beck depression inventory and Beck anxiety inventory scores in
      the study group were significantly higher compared to the control group. Thirteen
      patients in the study group attempted suicide, whereas 3 individuals attempted
      suicide in the control group. Similarly, the mean suicide behavior and ideation
      scores in the study group were significantly higher compared to the control
      group. The mean total multidimensional inventories of perceived social support
      score, as well as the mean family and friend sub-inventory scores in the control
      group were significantly higher compared to the study group. CONCLUSIONS: This
      study revealed that depression and anxiety occur frequently in cancer patients.
      Suicide attempts and ideation are higher in cancer patients compared to the
      control group. Social support perceived from family and friends is lower in
      cancer patients. Suicide attempts are correlated with depression, anxiety, low
      level of perceived social support, and advanced disease stage.

PMID- 24584173
TI  - Comparison of TIMI and Gensini score in patients admitted to the emergency
      department with chest pain, who underwent coronary angiography.
AB  - BACKGROUND: In patients admitted to the emergency department with complaints of
      chest pain and unstable angina pectoris, ST-elevation MI scoring is done
      according to risk factors used to calculate risks of urgent revascularization,
      MI, and death within 14 days. For this calculation, the most widely used scoring
      system is TIMI risk score. MATERIAL AND METHODS: In this prospective, cross
      sectional descriptive study, we evaluated and compared the effectiveness of TIMI
      and Gensini scores of patients with chest pain who were admitted to Hacettepe
      University Hospitals Emergency Department between March 2011 and September 2011
      and who underwent coronary angiography. RESULTS: The mean (range) age of 165
      patients was 62 (31-88) years. Moderate correlation between TIMI and Gensini
      scores was detected (mean values of Gensini score for TIMI 1 is 53.50, for TIMI 2
      it is 52.09, for TIMI 3 it is 102.77, for TIMI 4 it is 113.70, and for TIMI 5 it
      is 115.43). There was also a positive correlation between TIMI score and the
      results. CONCLUSIONS: TIMI risk stratification score is safe and easy to use for
      rapid assessment of mortality and MI risk, despite its low possibility of
      predicting the outcome.

PMID- 24584174
TI  - High-fidelity spin entanglement using optimal control.
AB  - Precise control of quantum systems is of fundamental importance in quantum
      information processing, quantum metrology and high-resolution spectroscopy. When
      scaling up quantum registers, several challenges arise: individual addressing of
      qubits while suppressing cross-talk, entangling distant nodes and decoupling
      unwanted interactions. Here we experimentally demonstrate optimal control of a
      prototype spin qubit system consisting of two proximal nitrogen-vacancy centres
      in diamond. Using engineered microwave pulses, we demonstrate single electron
      spin operations with a fidelity F~0.99. With additional dynamical decoupling
      techniques, we further realize high-quality, on-demand entangled states between
      two electron spins with F>0.82, mostly limited by the coherence time and
      imperfect initialization. Crosstalk in a crowded spectrum and unwanted dipolar
      couplings are simultaneously eliminated to a high extent. Finally, by high
      fidelity entanglement swapping to nuclear spin quantum memory, we demonstrate
      nuclear spin entanglement over a length scale of 25 nm. This experiment
      underlines the importance of optimal control for scalable room temperature spin
      based quantum information devices.

PMID- 24584175
TI  - Probucol suppresses macrophage infiltration and MMP expression in atherosclerotic
      plaques of WHHL rabbits.
AB  - AIM: Probucol is a lipid-lowering drug that is often prescribed for the treatment
      of familial hypercholesterolemia. However, it is not known whether probucol can
      change the lesion quality of atherosclerosis. METHODS: We examined this
      possibility using WHHL rabbits, a model of human familial hypercholesterolemia.
      Three-month-old male WHHL rabbits were treated with either probucol(85 mg/kg/day)
      or atorvastatin(6 mg/kg/day) for 16 weeks, and their plasma lipid levels and
      atherosclerotic lesions were compared with those of a control group. RESULTS: We
      found that probucol treatment reduced the plasma cholesterol levels, but less
      remarkably than atorvastatin treatment. In spite of this, probucol treatment led
      to a prominent reduction of aortic en face lesions by 39%(P<0.01), whereas
      atorvastatin reduced these by 16%(P>0.05), compared with those in the control.
      Histological examinations revealed that the aortic lesions of probucol-treated
      rabbits were characterized by reduced macrophages and increased smooth muscle
      cells compared with those from both the control and atorvastatin groups.
      Furthermore, probucol treatment reduced the coronary artery stenosis and
      increased the plaque stability. CONCLUSIONS: These results suggest that probucol
      treatment may have beneficial effects on the plaque stability of
      hypercholesterolemic patients.

PMID- 24584183
TI  - Advances in kilovoltage x-ray beam dosimetry.
AB  - This topical review provides an up-to-date overview of the theoretical and
      practical aspects of therapeutic kilovoltage x-ray beam dosimetry. Kilovoltage x
      ray beams have the property that the maximum dose occurs very close to the
      surface and thus, they are predominantly used in the treatment of skin cancers
      but also have applications for the treatment of other cancers. In addition,
      kilovoltage x-ray beams are used in intra operative units, within animal
      irradiators and in on-board imagers on linear accelerators and kilovoltage
      dosimetry is important in these applications as well. This review covers both
      reference and relative dosimetry of kilovoltage x-ray beams and provides
      recommendations for clinical measurements based on the literature to date. In
      particular, practical aspects for the selection of dosimeter and phantom material
      are reviewed to provide suitable advice for medical physicists. An overview is
      also presented of dosimeters other than ionization chambers which can be used for
      both relative and in vivo dosimetry. Finally, issues related to the treatment
      planning and the use of Monte Carlo codes for solving radiation transport
      problems in kilovoltage x-ray beams are presented. 

PMID- 24584176
TI  - Clinical impact of bisoprolol versus carvedilol in patients undergoing
      femoropopliteal stenting.
AB  - AIM: Beta-blockers are not considered to be contraindicated in patients with
      peripheral artery disease, and carvedilol and bisoprolol are commonly used in
      patients with PAD in Japan. Because there have been only a few reported
      comparative studies of the effects of different beta-blockers, we compared the
      clinical outcomes in patients treated with these beta-blockers after undergoing
      femoropopliteal stenting. METHODS: Between January 2004 and December 2011, 2911
      consecutive patients who had undergone their first femoropopliteal stenting were
      enrolled in this study. Of these patients, 438 patients(532 limbs) on
      carvedilol(187 patients, 229 limbs) or bisoprolol(251 patients, 303 limbs) were
      identified and analyzed retrospectively. The primary outcome was the primary
      patency and the secondary outcomes were the secondary patency and overall
      survival and freedom from major adverse limb events(MALE; including any repeated
      revascularization and major amputation), and these were compared between the
      groups. The mean follow-up interval of the survivors was 27+/-17 months. RESULTS:
      The primary patency was significantly higher in the bisoprolol-treated group than
      in the carvedilol-treated group(82.4% vs. 73.6% at 2 years, p=0.0006) as were the
      secondary patency (93.5% vs. 88.1% at two years, p=0.0004) and freedom from MALE
      (unadjusted: 79.6% vs. 67.9% at two years, p<0.0001). However, the two-year
      overall survival was similar between the groups(91.2% vs. 89.9% at two years,
      p=0.44). Even after adjusting for baseline differences, bisoprolol was still
      found to be significantly more effective for the primary patency (HR 0.56, 95% CI
      0.37 to 0.83, adjusted p=0.005). CONCLUSION: Our retrospective study suggests
      that bisoprolol is associated with more favorable outcomes for vessel patency and
      avoidance of MALE than is carvedilol.

PMID- 24584185
TI  - Membrane pacman: small steps for the voltage-sensitive phosphatases.

PMID- 24584186
TI  - Combined neonatal therapies for cardiac function in adulthood - live together,
      die alone?

PMID- 24584187
TI  - Malignant hyperthermia: to buffer or not to buffer.

PMID- 24584188
TI  - Fishing with flies, worms and bacteria: emerging models for mammalian membrane
      transport and trafficking.

PMID- 24584189
TI  - p53 N-terminal binding and stabilisation by PIAS3 inhibits MDM2-induced p53
      ubiquitination and regulates cell growth.
AB  - Mouse double minute 2 homolog (MDM2) binds to p53 through the 1-52 amino acid
      region of p53, in order to ubiquitinate p53. MDM2 thus destabilises p53 and
      inhibits the effect of p53 on cell cycle arrest and apoptosis. In the present
      study, the 1-52 amino acid region of the wild-type (wt) p53 protein was stably
      expressed in H1299 cells. The lysate of the transfected cells was then analysed
      using co-immunoprecipitation. A specific fraction of the precipitate was
      subjected to mass spectrometry analysis, which revealed that p53 bound to protein
      inhibitor of activated STAT3 (PIAS3). To the best of our knowledge, the present
      study is the first to report that the interaction of PIAS3 with p53 occurs
      through the 1-52 amino acid region of p53. Overexpression of PIAS3 in the A549 wt
      p53-expressing cell line was found to significantly increase the half-life of p53
      in the presence of cycloheximide, an inhibitor of protein synthesis. However,
      PIAS3 overexpression did not affect p53 mRNA levels. Furthermore, PIAS3
      overexpression was observed to decrease p53 ubiquitination. Protein-protein
      interaction analysis revealed that PIAS3 binds to the 1-52 amino acid region of
      p53, thus disrupts the formation of the p53-MDM2 complex. In addition,
      overexpression of PIAS3 in A549 cells was found to enhance the transcription of
      the p53-transactivated target p21/waf1, due to p53 accumulation, which led to an
      increase in p53 binding to the p21 gene promoter. These findings indicate that
      this newly identified p53-PIAS3 interaction through the 1-52 amino acid region of
      p53, reduces p53-MDM2 complex formation, which not only increases the half-life
      of p53, but also its transactivation of target genes.

PMID- 24584190
TI  - Towards a highly dispersed and more thermally stable Ru/OCNT catalyst.
AB  - A highly dispersed Ru/OCNT catalyst synthesized through a facile ethylene glycol
      reduction approach shows more uniform particle size distribution with ~1.0 nm
      compared with that prepared through a conventional impregnation method. Moreover,
      it also has good thermal stability evidenced by an in situ TEM study. 

PMID- 24584191
TI  - A coumarin-based fluorescent probe for recognition of Cu(2+) and fast detection
      of histidine in hard-to-transfect cells by a sensing ensemble approach.
AB  - A coumarin-based fluorescent chemosensor CAQA has been synthesized. It can
      selectively and sensitively recognize Cu(2+) in aqueous acetonitrile solutions.
      Using the Cu-containing complex CAQA-Cu(2+) as a sensing ensemble, the device
      demonstrates highly selective recognition of His/biothiols and was applied in
      fluorescence imaging of histidine in hard-to-transfect living cells. 

PMID- 24584192
TI  - Efficient genome modification by CRISPR-Cas9 nickase with minimal off-target
      effects.
AB  - Bacterial RNA-directed Cas9 endonuclease is a versatile tool for site-specific
      genome modification in eukaryotes. Co-microinjection of mouse embryos with Cas9
      mRNA and single guide RNAs induces on-target and off-target mutations that are
      transmissible to offspring. However, Cas9 nickase can be used to efficiently
      mutate genes without detectable damage at known off-target sites. This method is
      applicable for genome editing of any model organism and minimizes confounding
      problems of off-target mutations. 

PMID- 24584193
TI  - Highly multiplexed imaging of tumor tissues with subcellular resolution by mass
      cytometry.
AB  - Mass cytometry enables high-dimensional, single-cell analysis of cell type and
      state. In mass cytometry, rare earth metals are used as reporters on antibodies.
      Analysis of metal abundances using the mass cytometer allows determination of
      marker expression in individual cells. Mass cytometry has previously been applied
      only to cell suspensions. To gain spatial information, we have coupled
      immunohistochemical and immunocytochemical methods with high-resolution laser
      ablation to CyTOF mass cytometry. This approach enables the simultaneous imaging
      of 32 proteins and protein modifications at subcellular resolution; with the
      availability of additional isotopes, measurement of over 100 markers will be
      possible. We applied imaging mass cytometry to human breast cancer samples,
      allowing delineation of cell subpopulations and cell-cell interactions and
      highlighting tumor heterogeneity. Imaging mass cytometry complements existing
      imaging approaches. It will enable basic studies of tissue heterogeneity and
      function and support the transition of medicine toward individualized molecularly
      targeted diagnosis and therapies. 

PMID- 24584194
TI  - Structure determination of noncanonical RNA motifs guided by 1H NMR chemical
      shifts.
AB  - Structured noncoding RNAs underlie fundamental cellular processes, but
      determining their three-dimensional structures remains challenging. We
      demonstrate that integrating 1H NMR chemical shift data with Rosetta de novo
      modeling can be used to consistently determine high-resolution RNA structures. On
      a benchmark set of 23 noncanonical RNA motifs, including 11 'blind' targets,
      chemical-shift Rosetta for RNA (CS-Rosetta-RNA) recovered experimental structures
      with high accuracy (0.6-2.0 A all-heavy-atom r.m.s. deviation) in 18 cases.

PMID- 24584195
TI  - Live-cell imaging of alkyne-tagged small biomolecules by stimulated Raman
      scattering.
AB  - Sensitive and specific visualization of small biomolecules in living systems is
      highly challenging. We report stimulated Raman-scattering imaging of alkyne tags
      as a general strategy for studying a broad spectrum of small biomolecules in live
      cells and animals. We demonstrate this technique by tracking alkyne-bearing drugs
      in mouse tissues and visualizing de novo synthesis of DNA, RNA, proteins,
      phospholipids and triglycerides through metabolic incorporation of alkyne-tagged
      small precursors. 

PMID- 24584196
TI  - Knowledge of oral cancer, preventive attitudes, and behaviors of primary care
      physicians in Turkey.
AB  - Oral cancers (OCs) have a high mortality rate because of their typically late
      diagnosis. Primary care physicians play a vital role in early detection. In this
      study, we evaluated the family physicians' (FPs) knowledge, preventive attitudes,
      and behaviors in terms of OCs. A semistructured questionnaire consisting of 50
      questions was prepared and distributed to 200 FPs. Questions were grouped under
      four main headings: demographic characteristics, general protective attitudes
      against OCs, risk factors, and daily practices while performing the necessary
      examinations and referrals. Of 200 FPs, 164 responded to the questionnaire (82%
      response rate). The mean age of the study participants was 34.8 +/- 8.4 years and
      the mean duration of practice was 10 +/- 8.1 years. One-third of the physicians
      (29.9%, n=49) stated that they did not inquire about the amount of tobacco use.
      In terms of alcohol use, 45.7% (n=75) and 56.7% (n=93) did not ask about past
      alcohol consumption or the amount of alcohol consumed, respectively. Moreover,
      69.5% (n=114) believed that they did not receive adequate smoking cessation
      training and 79.9% (n=131) stated that they did not receive any alcohol cessation
      training. To decrease morbidity and mortality associated with OCs, primary care
      physicians should be trained to ask their patients about high-risk behaviors,
      provide counseling and education on tobacco and alcohol-abuse cessation, and
      provide oral examinations.

PMID- 24584197
TI  - Improving the reporting of evaluations of faecal immunochemical tests for
      haemoglobin: the FITTER standard and checklist.

PMID- 24584198
TI  - A novel mechanism for momordin Ic-induced HepG2 apoptosis: involvement of PI3K-
      and MAPK-dependent PPARgamma activation.
AB  - Momordin Ic is a natural triterpenoid saponin found in various Chinese and
      Japanese natural medicines such as the fruit of Kochia scoparia (L.) Schrad.
      Momordin Ic has been previously demonstrated to induce HepG2 cell apoptosis in a
      ROS-mediated PI3K and MAPK pathway-dependent manner. In the present study, the
      underlying mechanisms of PI3K and MAPK pathway-mediated PPARgamma, and PGC-1alpha
      co-regulator activation, as well as the effects of downstream proteins, COX-2 and
      FoxO4, on cell apoptosis were investigated. The results demonstrated that
      momordin Ic activated PPARgamma and inhibited COX-2. PGC-1alpha and FoxO4
      expressions were increased by the PI3K or MAPK pathways. Furthermore, PPARgamma
      inhibition decreased p-p38 and FoxO4 expression, and restored COX-2 expression.
      ROS inhibition exerted little effect on PPARgamma, COX-2 and FoxO4 expression but
      affected PGC-1alpha expression. These results revealed the involvement of PI3K
      and MAPK-dependent PPARgamma activation in momordin Ic-induced apoptosis,
      providing more detailed information underlying the pro-apoptotic mechanism of
      momordin Ic in HepG2 cell apoptosis. 

PMID- 24584199
TI  - HP1alpha mediates defective heterochromatin repair and accelerates senescence in
      Zmpste24-deficient cells.
AB  - Heterochromatin protein 1 (HP1) interacts with various proteins, including
      lamins, to play versatile functions within nuclei, such as chromatin remodeling
      and DNA repair. Accumulation of prelamin A leads to misshapen nuclei,
      heterochromatin disorganization, genomic instability, and premature aging in
      Zmpste24-null mice. Here, we investigated the effects of prelamin A on HP1alpha
      homeostasis, subcellular distribution, phosphorylation, and their contribution to
      accelerated senescence in mouse embryonic fibroblasts (MEFs) derived from
      Zmpste24(-/-) mice. The results showed that the level of HP1alpha was
      significantly increased in Zmpste24(-/-) cells. Although prelamin A interacted
      with HP1alpha in a manner similar to lamin A, HP1alpha associated with the
      nuclease-resistant nuclear matrix fraction was remarkably increased in Zmpste24(
      /-) MEFs compared with that in wild-type littermate controls. In wild-type cells,
      HP1alpha was phosphorylated at Thr50, and the phosphorylation was maximized
      around 30 min, gradually dispersed 2 h after DNA damage induced by camptothecin.
      However, the peak of HP1alpha phosphorylation was significantly compromised and
      appeared until 2 h, which is correlated with the delayed maximal formation of
      gamma-H2AX foci in Zmpste24(-/-) MEFs. Furthermore, knocking down HP1alpha by
      siRNA alleviated the delayed DNA damage response and accelerated senescence in
      Zmpste24(-/-) MEFs, evidenced by the rescue of the delayed gamma-H2AX foci
      formation, downregulation of p16, and reduction of senescence-associated beta
      galactosidase activity. Taken together, these findings establish a functional
      link between prelamin A, HP1alpha, chromatin remodeling, DNA repair, and early
      senescence in Zmpste24-deficient mice, suggesting a potential therapeutic
      strategy for laminopathy-based premature aging via the intervention of HP1alpha. 

PMID- 24584210
TI  - Two cases of warfarin-induced tracheobronchial calcification after Fontan
      surgery.
AB  - This study identified tracheobronchial cartilage calcification in children with
      congenital heart disease. Calcification of the tracheobronchial airways has been
      found previously in adults receiving warfarin and in children receiving warfarin
      after mitral valve replacement. A 9-year-old girl who had received a Fontan
      repair 6 years previously underwent a cardiac computed tomography (CT) scan to
      evaluate pulmonary artery size. The result was an incidental finding of extensive
      tracheobronchial cartilage calcification. A retrospective review of all pediatric
      Fontan patients who had undergone cardiac CT was conducted to search for
      calcification of the tracheobronchial cartilage. The study investigated ten
      pediatric Fontan patients who had undergone cardiac CT scanning. Two patients
      with extensive calcification of the tracheobronchial airways were identified. The
      index case had hypoplastic left heart syndrome, and the patient had undergone a
      staged repair with the Fontan at the age of 3 years. A 16-year-old boy with
      tricuspid atresia had undergone staged repair and Fontan at the age of 3.5 years.
      These two patients had received continuous warfarin therapy for 6 and 13 years,
      respectively. Other common causes of airway calcification were excluded from the
      study. This report describes warfarin-induced tracheobronchial calcification in
      patients after the Fontan procedure. This finding has possible implications for
      airway growth and vascular calcification.

PMID- 24584211
TI  - Comparison of pressure-volume loop and echocardiographic measures of diastolic
      function in patients with a single-ventricle physiology.
AB  - Echocardiographic measurements of diastolic function have not been validated
      against invasive pressure-volume loop (PVL) analysis in the single-ventricle
      population. The authors hypothesized that echocardiographic measures of diastolic
      function would correlate with PVL indices of diastolic function in patients with
      a single-ventricle physiology. The conductance-derived PVL measures of diastolic
      function included the isovolumic relaxation time constant (tau), the maximum rate
      of ventricular pressure decline (peak -dP/dt), and a measure of passive diastolic
      stiffness (MU). The echocardiographic measures included Doppler inflow patterns
      of the dominant atrioventricular valve (DAVV), tissue Doppler velocities (TDI) at
      the lateral (ventricular free wall) component of the DAVV annulus, and the TDI
      derived isovolumic relaxation time (IVRT'). The correlation between PVL and
      echocardiographic measures was examined. The study enrolled 13 patients at
      various stages of surgical palliation. The median age of the patients was 3 years
      (range 3 months to 19 years). tau correlated well with Doppler E:A (r = 0.832; p
      = 0.005), lateral E:E' (r = 0.747; p = 0.033), and IVRT' (r = 0.831; p = 0.001).
      Peak -dP/dt also was correlated with IVRT' (r = 0.609; p = 0.036), and MU also
      was correlated with IVRT' (r = 0.884; p = 0.001). This study represents the first
      ever comparison of diastolic echocardiographic and PVL indices in a single
      ventricle population. The findings show that Doppler E:A, lateral E:E', and IVRT'
      correlate well with PVL measures of diastolic function. This study supports
      further validation of echocardiographic measures of diastolic function versus PVL
      measures of diastolic function in the single-ventricle population.

PMID- 24584212
TI  - Spatial and temporal overview of research in pediatric and congenital cardiology:
      trends and global challenges.
AB  - Available information on the global distribution of research output in pediatric
      cardiology (PC) is sparse. This study took a bibliometric approach to
      characterize research output, assess the level of competition, describe the
      geographic distribution of the leading research centers in the field, and
      investigate determinants of research output. In addition, the study characterized
      the journals publishing PC research and identified temporal trends in research
      interest over time. Publications presenting original research in PC between 1995
      and 2011 were identified. A total of 9,410 relevant articles were identified
      based on a PubMed search followed by subsequent electronic filtering and manual
      review. A dramatic increase in PC publications was seen during the study period
      (from 309 in 1995 to 1,075 in 2011). This was accompanied by an increase in
      impact factors and an overproportional rise in PC contributions relative to the
      general PubMed trend. Research in PC was shown to be highly competitive and
      becoming increasingly so (Herfindahl-Hirschman index of 1.64%). Research output
      correlated with gross domestic product, national levels of corruption, education,
      urbanization, geography, and presence of national centers of excellence. The data
      presented in this report allow benchmarking of different cities and countries and
      provide insights into the potential determinants of high-quality publications and
      the spectrum of publishing journals. The report also highlights the central role
      of subspecialty journals and shows that PC research output is related to national
      wealth, surrogates of appropriate use of resources, an adequate workforce, and
      education. Additionally, it emphasizes the potential beneficial effects of
      establishing centers of excellence in the field.

PMID- 24584213
TI  - Interactive MRI Segmentation with Controlled Active Vision.
AB  - Partitioning Magnetic-Resonance-Imaging (MRI) data into salient anatomic
      structures is a problem in medical imaging that has continued to elude fully
      automated solutions. Implicit functions are a common way to model the boundaries
      between structures and are amenable to control-theoretic methods. In this paper,
      the goal of enabling a human to obtain accurate segmentations in a short amount
      of time and with little effort is transformed into a control synthesis problem.
      Perturbing the state and dynamics of an implicit function's driving partial
      differential equation via the accumulated user inputs and an observer-like system
      leads to desirable closed-loop behavior. Using a Lyapunov control design, a
      balance is established between the influence of a data-driven gradient flow and
      the human's input over time. Automatic segmentation is thus smoothly coupled with
      interactivity. An application of the mathematical methods to orthopedic
      segmentation is shown, demonstrating the expected transient and steady state
      behavior of the implicit segmentation function and auxiliary observer.

PMID- 24584214
TI  - Design of a variable-stiffness flapping mechanism for maximizing the thrust of a
      bio-inspired underwater robot.
AB  - Compliance can increase the thrust generated by the fin of a bio-inspired
      underwater vehicle. To improve the performance of a compliant fin, the compliance
      should change with the operating conditions; a fin should become stiffer as the
      oscillating frequency increases. This paper presents a novel variable-stiffness
      flapping (VaSF) mechanism that can change its stiffness to maximize the thrust of
      a bio-inspired underwater robot. The mechanism is designed on the basis of an
      endoskeleton structure, composed of compliant and rigid segments alternately
      connected in series. To determine the attachment point of tendons, the anatomy of
      a dolphin's fluke is considered. Two tendons run through the mechanism to adjust
      the stiffness. The fluke becomes stiffer when the tendons are pulled to compress
      the structure. The thrust generated by a prototype mechanism is measured under
      different conditions to show that the thrust can be maximized by changing the
      stiffness. The thrust of the VaSF device can approximately triple at a certain
      frequency just by changing the stiffness. This VaSF mechanism can be used to
      improve the efficiency of a bio-inspired underwater robot that uses compliance. 

PMID- 24584215
TI  - Impaired heart rate recovery indices in psoriasis patients.
AB  - BACKGROUND: Psoriasis is a systemic inflammatory disease associated with
      increased risk of cardiovascular diseases. The heart rate recovery index (HRRI)
      is an indicator of autonomic nervous system function and is an independent
      prognostic risk factor for cardiovascular diseases. The aim of this study was to
      evaluate the heart rate recovery indices in patients with psoriasis. MATERIAL AND
      METHODS: Thirty-three psoriasis patients (22 male; mean age 41 +/- 11 years) and
      26 healthy individuals (15 male; mean age 39 +/- 11 years) as a control group
      were included in the study. Baseline electrocardiography, transthoracic
      echocardiographic examinations, and exercise stress tests were performed in
      psoriasis and control groups. The heart rate recovery of the psoriasis group at
      1, 2, 3, 4, and 5 minutes after maximal exercise were calculated and compared to
      those of the control group. RESULTS: Baseline demographic and clinical
      characteristics of psoriasis and control groups including age, sex, body mass
      index, systolic blood pressure, and echocardiographic parameters were similar.
      Total cholesterol, low-density lipoprotein cholesterol, and triglyceride levels
      were significantly higher and high-density lipoprotein cholesterol levels were
      significantly lower in the psoriasis group (p<0.05). Heart rate recovery at 1, 2,
      3, 4, and 5 minutes after maximal exercise were found to be significantly lower
      in the psoriasis group (p<0.05). Additionally, baseline heart rates before
      exercise were significantly higher in the psoriasis group (p<0.05). CONCLUSIONS:
      We found that impaired HRRI in psoriasis patients, which indicates the underlying
      autonomic nervous system dysfunction, is a pathophysiologic mechanism for
      increased cardiovascular disease risk.

PMID- 24584216
TI  - Prevalence of second premolar hypodontia in the Polish cleft lip and palate
      population.
AB  - BACKGROUND: Cleft lip and/or palate is the most frequent congenital abnormality
      occurring in the craniofacial region and is often associated with numerous dental
      defects such as tooth agenesis, supernumerary teeth, microdontia, taurodontism,
      crown malformations, or delay in eruption. The prevalence of hypodontia in cleft
      affected patients is much higher in comparison with a healthy population. The aim
      of this study was to evaluate the prevalence of second premolar hypodontia in
      patients with cleft lip and/or palate. MATERIAL AND METHODS: We performed a
      retrospective, evaluation of panoramic radiographs and dental casts in the
      Department of Dentofacial Orthopeadics and Orthodontics, Wroclaw Medical
      University. Two independent observers evaluated the records of 469 patients with
      various types of clefts and analyzed dental casts and panoramic radiographs.
      RESULTS: 202 individuals met inclusion criteria. The sample comprised 120 UCLP
      patients, 38 BCLP patients, 28 CP patients, and 17 CLA patients. Hypodontia in
      the premolar region was observed in 39 individuals (19.3%). A total number of 58
      second premolars were missing, of which 35 were maxillary second premolars (U5)
      and 23 were mandibular second premolars (L5). CONCLUSIONS: Estimated hypodontia
      in the Polish CL/P sample was considerably higher than the hypodontia in
      permanent dentition reported for a European healthy population. The number of
      congenitally missing second premolars was higher in the maxillary arch than in
      the mandibular.

PMID- 24584217
TI  - Differential regional lung uptake analysis of the lung scan as an adjunct to
      interpretation of pulmonary embolism.
AB  - OBJECTIVE: Differential regional lung uptake (DRLU) analysis of a lung perfusion
      scan is used to provide information on diversion of the radiotracer from areas
      supplied by obstructed pulmonary artery branches to areas with patent vessels,
      which could assist in the diagnosis of pulmonary embolism (PE), especially the
      intermediate-probability studies. METHODS: Lung perfusion scans performed over 3
      years (n=121) were analyzed using a computer overlay of six regions of interest
      per lung on the posterior view. DRLU was defined for neighboring region pairs as
      the ratio of the difference in the average count rate to the sum of the count
      rate in the region pair for a total of 18 region pairs per study. RESULTS:
      Comparison of the DRLU for high-probability studies (n=30) with normal scans
      (n=40) showed significant deviation in a least three region pairs per study. For
      low-probability scans (n=30), there was no significant deviation from the normal.
      For the intermediate category (n=21), a subgroup (n=7) showed significant
      deviation in at least three region pairs, which also had a positive computed
      tomography pulmonary angiography for PE, and another subgroup (n=14) had
      deviation in two or fewer region pairs with a negative computed tomography
      pulmonary angiography. CONCLUSION: Using DRLU analysis, intermediate scans for PE
      could be redefined as low or high probability, on the basis of the number of
      region pairs showing deviation of DRLU. This could lead to improved diagnostic
      performance of the study without recourse to additional maneuvers or specialized
      equipment and would obviate the need for more tests on the patient.

PMID- 24584218
TI  - Radiation protection procedures in 131I treatments for thyroid cancer in patients
      requiring hemodialysis.
AB  - BACKGROUND: Hemodialysis is essential for patients with renal failure, and iodine
      131 ((131)I) administration is the standard of care in thyroid carcinoma
      treatment. Although the need for hemodialysis during (131)I treatment is very
      rare, it raises some concerns due to the involvement of personnel not exposed to
      radiation and to the contamination of devices used for other patients. In this
      paper, a radioprotection protocol to perform hemodialysis safely on patients
      during (131)I treatment has been presented. PATIENTS AND METHODS: The exposure of
      personnel who assisted 13 patients over the course of 10 years was monitored:
      external exposure was measured through electronic dosimeters, and internal
      contamination was checked by thyroid uptake and urine sample gamma spectrometry.
      Over this period, room layout was optimized to allow an improvement of
      radioprotection procedures.Two nurses were involved in patient assistance.
      RESULTS: After hemodialysis, measurements of internal contamination were below
      the minimum detectable activity and external exposure was in the range of 1-82
      MUSv in terms of H(p)(10). A reduction in personnel exposure was observed after
      hospitalization room renovation: H(p)(10) normalized to the activity administered
      to the patient was about halved. CONCLUSION: The data show that hemodialysis can
      be performed safely during I treatments when appropriate radioprotection actions
      are implemented.

PMID- 24584219
TI  - Work performance assessed by a newly developed Japanese version of the Work
      Limitation Questionnaire in a general Japanese adult population.
AB  - BACKGROUND: The Work Limitations Questionnaire (WLQ) was recently developed to
      measure health-related decrements in ability to perform job roles among employed
      individuals. The purpose of this study was to develop and test a Japanese version
      of the WLQ. METHODS: Developing the Japanese version of the WLQ involved
      translations, back-translations, and a pilot study. Using data obtained from a
      nationwide survey, 4,600 people aged >=20 years were selected from the entire
      population of Japan by stratified random sampling. We ultimately used data from a
      total of 1,358 workers out of 2,266 subjects who filled out the self-administered
      questionnaire. We computed the proportion of missing data, measured internal
      consistency reliability, and tested for convergent and discriminant validity,
      concurrent validity, known-groups validity, and the factor structure of this
      instrument. RESULTS: For the Japanese version of the WLQ, the percentages of
      missing values for each scale ranged from 3.6% to 7.8%. Internal consistency
      reliability was high, and Cronbach's alpha was >=0.7 for all subscales. Subjects
      with headache and orthopedic pain had significantly higher WLQ subscale scores
      than subjects without. Higher WLQ subscale scores were associated with depressive
      symptoms as measured with the Hospital Anxiety and Depression Scale (p<0.001).
      CONCLUSIONS: The Japanese WLQ provides reliable and valid information on at-work
      disability for group-level comparisons and tracking therapeutic outcomes.

PMID- 24584220
TI  - Orbital-selective spin texture and its manipulation in a topological insulator.
AB  - Topological insulators represent a new quantum state of matter that are
      insulating in the bulk but metallic on the edge or surface. In the Dirac surface
      state, it is well-established that the electron spin is locked with the crystal
      momentum. Here we report a new phenomenon of the spin texture locking with the
      orbital texture in a topological insulator Bi2Se3. We observe light-polarization
      dependent spin texture of both the upper and lower Dirac cones that constitutes
      strong evidence of the orbital-dependent spin texture in Bi2Se3. The different
      spin texture detected in variable polarization geometry is the manifestation of
      the spin-orbital texture in the initial state combined with the photoemission
      matrix element effects. Our observations provide a new orbital degree of freedom
      and a new way of light manipulation in controlling the spin structure of the
      topological insulators that are important for their future applications in spin
      related technologies.

PMID- 24584221
TI  - Physiological minimum temperatures for root growth in seven common European broad
      leaved tree species.
AB  - Temperature is the most important factor driving the cold edge distribution limit
      of temperate trees. Here, we identified the minimum temperatures for root growth
      in seven broad-leaved tree species, compared them with the species' natural
      elevational limits and identified morphological changes in roots produced near
      their physiological cold limit. Seedlings were exposed to a vertical soil
      temperature gradient from 20 to 2  degrees C along the rooting zone for 18 weeks.
      In all species, the bulk of roots was produced at temperatures above 5  degrees
      C. However, the absolute minimum temperatures for root growth differed among
      species between 2.3 and 4.2  degrees C, with those species that reach their
      natural distribution limits at higher elevations also tending to have lower
      thermal limits for root tissue formation. In all investigated species, the roots
      produced at temperatures close to the thermal limit were pale, thick, unbranched
      and of reduced mechanical strength. Across species, the specific root length (m
      g(-1) root) was reduced by, on average, 60% at temperatures below 7  degrees C. A
      significant correlation of minimum temperatures for root growth with the natural
      high elevation limits of the investigated species indicates species-specific
      thermal requirements for basic physiological processes. Although these limits are
      not necessarily directly causative for the upper distribution limit of a species,
      they seem to belong to a syndrome of adaptive processes for life at low
      temperatures. The anatomical changes at the cold limit likely hint at the
      mechanisms impeding meristematic activity at low temperatures. 

PMID- 24584238
TI  - Phasin proteins activate Aeromonas caviae polyhydroxyalkanoate (PHA) synthase but
      not Ralstonia eutropha PHA synthase.
AB  - In this study, we performed in vitro and in vivo activity assays of
      polyhydroxyalkanoate (PHA) synthases (PhaCs) in the presence of phasin proteins
      (PhaPs), which revealed that PhaPs are activators of PhaC derived from Aeromonas
      caviae (PhaCAc). In in vitro assays, among the three PhaCs tested, PhaCAc was
      significantly activated when PhaPs were added at the beginning of polymerization
      (prepolymerization PhaCAc), whereas the prepolymerization PhaCRe (derived from
      Ralstonia eutropha) and PhaCDa (Delftia acidovorans) showed reduced activity with
      PhaPs. The PhaP-activated PhaCAc showed a slight shift of substrate preference
      toward 3-hydroxyhexanoyl-CoA (C6). PhaPAc also activated PhaCAc when it was added
      during polymerization (polymer-elongating PhaCAc), while this effect was not
      observed for PhaCRe. In an in vivo assay using Escherichia coli TOP10 as the host
      strain, the effect of PhaPAc expression on PHA synthesis by PhaCAc or PhaCRe was
      examined. As PhaPAc expression increased, PHA production was increased by up to
      2.3-fold in the PhaCAc-expressing strain, whereas it was slightly increased in
      the PhaCRe-expressing strain. Taken together, this study provides evidence that
      PhaPs function as activators for PhaCAc both in vitro and in vivo but do not
      activate PhaCRe. This activating effect may be attributed to the new role of
      PhaPs in the polymerization reaction by PhaCAc. 

PMID- 24584239
TI  - Metabolic changes in Klebsiella oxytoca in response to low oxidoreduction
      potential, as revealed by comparative proteomic profiling integrated with flux
      balance analysis.
AB  - Oxidoreduction potential (ORP) is an important physiological parameter for
      biochemical production in anaerobic or microaerobic processes. However, the
      effect of ORP on cellular physiology remains largely unknown, which hampers the
      design of engineering strategies targeting proteins associated with ORP response.
      Here we characterized the effect of altering ORP in a 1,3-propanediol producer,
      Klebsiella oxytoca, by comparative proteomic profiling combined with flux balance
      analysis. Decreasing the extracellular ORP from -150 to -240 mV retarded cell
      growth and enhanced 1,3-propanediol production. Comparative proteomic analysis
      identified 61 differentially expressed proteins, mainly involved in carbohydrate
      catabolism, cellular constituent biosynthesis, and reductive stress response. A
      hypothetical oxidoreductase (HOR) that catalyzes 1,3-propanediol production was
      markedly upregulated, while proteins involved in biomass precursor synthesis were
      downregulated. As revealed by subsequent flux balance analysis, low ORP induced a
      metabolic shift from glycerol oxidation to reduction and rebalancing of redox and
      energy metabolism. From the integrated protein expression profiles and flux
      distributions, we can construct a rational analytic framework that elucidates how
      (facultative) anaerobes respond to extracellular ORP changes. 

PMID- 24584240
TI  - Structural basis of the divergent oxygenation reactions catalyzed by the rieske
      nonheme iron oxygenase carbazole 1,9a-dioxygenase.
AB  - Carbazole 1,9a-dioxygenase (CARDO), a Rieske nonheme iron oxygenase (RO), is a
      three-component system composed of a terminal oxygenase (Oxy), ferredoxin, and a
      ferredoxin reductase. Oxy has angular dioxygenation activity against carbazole.
      Previously, site-directed mutagenesis of the Oxy-encoding gene from
      Janthinobacterium sp. strain J3 generated the I262V, F275W, Q282N, and Q282Y Oxy
      derivatives, which showed oxygenation capabilities different from those of the
      wild-type enzyme. To understand the structural features resulting in the
      different oxidation reactions, we determined the crystal structures of the
      derivatives, both free and complexed with substrates. The I262V, F275W, and Q282Y
      derivatives catalyze the lateral dioxygenation of carbazole with higher yields
      than the wild type. A previous study determined the crystal structure of Oxy
      complexed with carbazole and revealed that the carbonyl oxygen of Gly178 hydrogen
      bonds with the imino nitrogen of carbazole. In these derivatives, the carbazole
      was rotated approximately 15, 25, and 25 degrees , respectively, compared to the
      wild type, creating space for a water molecule, which hydrogen bonds with the
      carbonyl oxygen of Gly178 and the imino nitrogen of carbazole. In the crystal
      structure of the F275W derivative complexed with fluorene, C-9 of fluorene, which
      corresponds to the imino nitrogen of carbazole, was oriented close to the mutated
      residue Trp275, which is on the opposite side of the binding pocket from the
      carbonyl oxygen of Gly178. Our structural analyses demonstrate that the fine
      tuning of hydrophobic residues on the surface of the substrate-binding pocket in
      ROs causes a slight shift in the substrate-binding position that, in turn, favors
      specific oxygenation reactions toward various substrates.

PMID- 24584241
TI  - Altered transcription of murine genes induced in the small bowel by
      administration of probiotic strain Lactobacillus rhamnosus HN001.
AB  - Lactobacillus rhamnosus HN001 is a probiotic strain reported to increase
      resistance to epithelium-adherent and -invasive intestinal pathogens in
      experimental animals. To increase understanding of the relationship between
      strain HN001 and the bowel, transcription of selected genes in the mucosa of the
      murine small bowel was measured. Mice previously naive to lactobacilli
      (Lactobacillus-free mice) were examined after daily exposure to HN001 in drinking
      water. Comparisons were made to results from matched Lactobacillus-free mice.
      Infant and adult mice were investigated to provide a temporal view of gene
      expression in response to exposure to HN001. Genes sgk1, angptl4, and hspa1b,
      associated with the apoptosis pathway, were selected for investigation by reverse
      transcription-quantitative PCR on the basis of a preliminary duodenal DNA
      microarray screen. Normalized to gapdh gene transcription, these three genes were
      upregulated after 6 to 10 days exposure of adult mice to HN001. Angptl4 was shown
      by immunofluorescence to be upregulated in duodenal epithelial cells of mucosal
      samples. Epithelial cell migration was faster in HN001-exposed mice than in the
      Lactobacillus-free controls. Transcriptional responses in infant mice differed
      according to bowel region and age. For example, sgk1 was upregulated in duodenal,
      jejunal, and ileal mucosa of mice less than 25 days old, whereas angptl4 and
      hspa1b were upregulated at 10 days in the duodenum but downregulated in the
      jejunal mucosa until mice were 25 days old. Overall, the results provide links
      between a probiotic strain, mucosal gene expression, and host phenotype, which
      may be useful in delineating mechanisms of probiotic action. 

PMID- 24584242
TI  - Effects of leachate from crumb rubber and zinc in green roofs on the survival,
      growth, and resistance characteristics of Salmonella enterica subsp. enterica
      serovar Typhimurium.
AB  - The use of green roofs is a growing practice worldwide, particularly in densely
      populated areas. In an attempt to find new methods for recycling crumb rubber,
      incorporation of crumb rubber into artificial medium for plant growth in green
      roofs and similar engineered environments has become an attractive option for the
      recycling of waste tires. Though this approach decreases waste in landfills,
      there are concerns about the leaching of zinc and other heavy metals, as well as
      nutrient and organic compounds, into the environment. The present study analyzed
      the impact of leachate from crumb rubber and zinc on the growth and viability of
      Salmonella enterica subsp. enterica serovar Typhimurium. Zinc was chosen for
      further studies since it has been previously implicated with other biological
      functions, including biofilm formation, motility, and possible cross-resistance
      to antimicrobial agents. The study showed that Salmonella can colonize crumb
      rubber and that crumb rubber extract may provide nutrients that are usable by
      this bacterium. Salmonella strains with reduced susceptibility (SRS) to zinc were
      obtained after subculturing in increasing concentrations of zinc. The SRS
      exhibited differences in gene expression of flux pump genes zntA and znuA
      compared to that of the parent when exposed to 20 mM added zinc. In biofilm
      formation studies, the SRS formed less biofilm but was more motile than the
      parental strain. 

PMID- 24584243
TI  - Expression of fluorescent proteins in bifidobacteria for analysis of host-microbe
      interactions.
AB  - Bifidobacteria are an important component of the human gastrointestinal
      microbiota and are frequently used as probiotics. The genetic inaccessibility and
      lack of molecular tools commonly used in other bacteria have hampered a detailed
      analysis of the genetic determinants of bifidobacteria involved in their
      adaptation to, colonization of, and interaction with the host. In the present
      study, a range of molecular tools were developed that will allow the closing of
      some of the gaps in functional analysis of bifidobacteria. A number of promoters
      were tested for transcriptional activity in Bifidobacterium bifidum S17 using
      pMDY23, a previously published promoter probe vector. The promoter of the gap
      gene (Pgap) of B. bifidum S17 yielded the highest promoter activity among the
      promoters tested. Thus, this promoter and the pMDY23 backbone were used to
      construct a range of vectors for expression of different fluorescent proteins
      (FPs). Successful expression of cyan fluorescent protein (CFP), green fluorescent
      protein (GFP), yellow fluorescent protein (YFP), and mCherry could be shown for
      three strains representing three different Bifidobacterium spp. The red
      fluorescent B. bifidum S17/pVG-mCherry was further used to demonstrate
      application of fluorescent bifidobacteria for adhesion assays and detection in
      primary human macrophages cultured in vitro. Furthermore, pMGC-mCherry was cloned
      by combining a chloramphenicol resistance marker and expression of the FP mCherry
      under the control of Pgap. The chloramphenicol resistance marker of pMGC-mCherry
      was successfully used to determine gastrointestinal transit time of B. bifidum
      S17. Moreover, B. bifidum S17/pMGC-mCherry could be detected in fecal samples of
      mice after oral administration. 

PMID- 24584245
TI  - Occurrence of an environmental Acinetobacter baumannii strain similar to a
      clinical isolate in paleosol from Croatia.
AB  - Over the past decade, bacteria of the genus Acinetobacter have emerged as a
      leading cause of hospital-acquired infections. Outbreaks of Acinetobacter
      infections are considered to be caused exclusively by contamination and
      transmission in hospital environments. The natural habitats of clinically
      important multiresistant Acinetobacter spp. remain to be defined. In this paper,
      we report an incidental finding of a viable multidrug-resistant strain of
      Acinetobacter baumannii, related to clinical isolates, in acid paleosol from
      Croatia. The environmental isolate of A. baumannii showed 87% similarity to a
      clinical isolate originating from a hospital in this geographic area and was
      resistant to gentamicin, trimethoprim-sulfamethoxazole, ciprofloxacin, and
      levofloxacin. In paleosol, the isolate was able to survive a low pH (3.37),
      desiccation, and a high temperature (50 degrees C). The probable source of A.
      baumannii in paleosol is illegally disposed waste of external origin situated in
      the abandoned quarry near the sampling site. The bacteria could have been leached
      from waste by storm water and thus infiltrated the paleosol. 

PMID- 24584244
TI  - Analysis of the microbial community structure by monitoring an Hg methylation
      gene (hgcA) in paddy soils along an Hg gradient.
AB  - Knowledge of the diversity of mercury (Hg)-methylating microbes in the
      environment is limited due to a lack of available molecular biomarkers. Here, we
      developed novel degenerate PCR primers for a key Hg-methylating gene (hgcA) and
      amplified successfully the targeted genes from 48 paddy soil samples along an Hg
      concentration gradient in the Wanshan Hg mining area of China. A significant
      positive correlation was observed between hgcA gene abundance and methylmercury
      (MeHg) concentrations, suggesting that microbes containing the genes contribute
      to Hg methylation in the sampled soils. Canonical correspondence analysis (CCA)
      showed that the hgcA gene diversity in microbial community structures from paddy
      soils was high and was influenced by the contents of total Hg, SO4(2-), NH4(+),
      and organic matter. Phylogenetic analysis showed that hgcA microbes in the
      sampled soils likely were related to Deltaproteobacteria, Firmicutes,
      Chloroflexi, Euryarchaeota, and two unclassified groups. This is a novel report
      of hgcA diversity in paddy habitats, and results here suggest a link between Hg
      methylating microbes and MeHg contamination in situ, which would be useful for
      monitoring and mediating MeHg synthesis in soils. 

PMID- 24584246
TI  - Adaptation of Escherichia coli to elevated sodium concentrations increases cation
      tolerance and enables greater lactic acid production.
AB  - Adaptive evolution was employed to generate sodium (Na(+))-tolerant mutants of
      Escherichia coli MG1655. Four mutants with elevated sodium tolerance, designated
      ALS1184, ALS1185, ALS1186, and ALS1187, were independently isolated after 73 days
      of serial transfer in medium containing progressively greater Na(+)
      concentrations. The isolates also showed increased tolerance of K(+), although
      this cation was not used for selective pressure. None of the adapted mutants
      showed increased tolerance to the nonionic osmolyte sucrose. Several
      physiological parameters of E. coli MG1655 and ALS1187, the isolate with the
      greatest Na(+) tolerance, were calculated and compared using glucose-limited
      chemostats. Genome sequencing showed that the ALS1187 isolate contained mutations
      in five genes, emrR, hfq, kil, rpsG, and sspA, all of which could potentially
      affect the ability of E. coli to tolerate Na(+). Two of these genes, hfq and
      sspA, are known to be involved in global regulatory processes that help cells
      endure a variety of cellular stresses. Pyruvate formate lyase knockouts were
      constructed in strains MG1655 and ALS1187 to determine whether increased Na(+)
      tolerance afforded increased anaerobic generation of lactate. In fed-batch
      fermentations, E. coli ALS1187 pflB generated 76.2 g/liter lactate compared to
      MG1655 pflB, which generated only 56.3 g/liter lactate. 

PMID- 24584247
TI  - Abiotic factors affecting the persistence of avian influenza virus in surface
      waters of waterfowl habitats.
AB  - Avian influenza (AI) virus can remain infectious in water for months, and virus
      contaminated surface water is considered to be a source of infection within wild
      waterfowl populations. Previous work has characterized the effects of pH,
      salinity, and temperature on viral persistence in water, but most of that work
      was done with modified distilled water. The objective of this study was to
      identify the abiotic factors that influence the duration of AI virus persistence
      in natural surface water. Surface water samples were collected from 38 waterfowl
      habitats distributed across the United States. Samples were submitted to the U.S.
      Geological Survey National Water Quality Laboratory for chemical analysis and the
      University of Georgia for viral reduction time analysis. Samples were filtered
      with 0.22-MUm filters, and the durations of persistence of three wild-bird
      derived influenza A viruses within each water sample at 10, 17, and 28 degrees C
      were determined. The effects of the surface water physicochemical factors on the
      duration of AI viral persistence in laboratory experiments were evaluated by
      multivariable linear regression with robust standard errors. The duration of AI
      virus persistence was determined to be longest in filtered surface water with a
      low temperature (<17 degrees C), a neutral-to-basic pH (7.0 to 8.5), low salinity
      (<0.5 ppt), and a low ammonia concentration (<0.5 mg/liter). Our results also
      highlighted potential strain-related variation in the stability of AI virus in
      surface water. These results bring us closer to being able to predict the
      duration of AI virus persistence in surface water of waterfowl habitats. 

PMID- 24584248
TI  - Microaerobic conversion of glycerol to ethanol in Escherichia coli.
AB  - Glycerol has become a desirable feedstock for the production of fuels and
      chemicals due to its availability and low price, but many barriers to
      commercialization remain. Previous investigators have made significant
      improvements in the yield of ethanol from glycerol. We have developed a
      fermentation process for the efficient microaerobic conversion of glycerol to
      ethanol by Escherichia coli that presents solutions to several other barriers to
      commercialization: rate, titer, specific productivity, use of inducers, use of
      antibiotics, and safety. To increase the rate, titer, and specific productivity
      to commercially relevant levels, we constructed a plasmid that overexpressed
      glycerol uptake genes dhaKLM, gldA, and glpK, as well as the ethanol pathway gene
      adhE. To eliminate the cost of inducers and antibiotics from the fermentation, we
      used the adhE and icd promoters from E. coli in our plasmid, and we implemented
      glycerol addiction to retain the plasmid. To address the safety issue of off-gas
      flammability, we optimized the fermentation process with reduced-oxygen sparge
      gas to ensure that the off-gas remained nonflammable. These advances represent
      significant progress toward the commercialization of an E. coli-based glycerol-to
      ethanol process. 

PMID- 24584249
TI  - Genetic diversity analysis reveals that geographical environment plays a more
      important role than rice cultivar in Villosiclava virens population selection.
AB  - Rice false smut caused by Villosiclava virens is an economically important
      disease of grains worldwide. The genetic diversity of 153 isolates from six
      fields located in Wuhan (WH), Yichang Wangjia (YCW), Yichang Yaohe (YCY),
      Huanggang (HG), Yangxin (YX), and Jingzhou (JZ) in Hubei province of China were
      phylogenetically analyzed to evaluate the influence of environments and rice
      cultivars on the V. virens populations. Isolates (43) from Wuhan were from two
      rice cultivars, Wanxian 98 and Huajing 952, while most of the other isolates from
      fields YCW, YCY, HG, YX, and JZ originated from different rice cultivars with
      different genetic backgrounds. Genetic diversity of isolates was analyzed using
      random amplified polymorphic DNA (RAPD) and single-nucleotide polymorphisms
      (SNP). The isolates from the same cultivars in Wuhan tended to group together,
      indicating that the cultivars had an important impact on the fungal population.
      The 110 isolates from individual fields tended to cluster according to
      geographical origin. The values of Nei's gene diversity (H) and Shannon's
      information index (I) showed that the genetic diversity among isolates was higher
      between than within geographical populations. Furthermore, mean genetic distance
      between groups (0.006) was higher than mean genetic distance within groups
      (0.0048) according to MEGA 5.2. The pairwise population fixation index (FST)
      values also showed significant genetic differentiation between most populations.
      Higher genetic similarity of isolates from individual fields but different rice
      cultivars suggested that the geographical factor played a more important role in
      the selection of V. virens isolates than rice cultivars. This information could
      be used to improve the management strategy for rice false smut by adjusting the
      cultivation measures, such as controlling fertilizer, water, and planting
      density, in the rice field to change the microenvironment. 

PMID- 24584250
TI  - Environmental dependence of stationary-phase metabolism in Bacillus subtilis and
      Escherichia coli.
AB  - When microbes lack the nutrients necessary for growth, they enter stationary
      phase. In cases when energy sources are still present in the environment, they
      must decide whether to continue to use their metabolic program to harvest the
      available energy. Here we characterized the metabolic response to a variety of
      types of nutrient starvation in Escherichia coli and Bacillus subtilis. We found
      that E. coli exhibits a range of phenotypes, with the lowest metabolic rates
      under nitrogen starvation and highest rates under magnesium starvation. In
      contrast, the phenotype of B. subtilis was dominated by its decision to form
      metabolically inactive endospores. While its metabolic rates under most
      conditions were thus lower than those of E. coli, when sporulation was suppressed
      by a genetic perturbation or an unnatural starvation condition, the situation was
      reversed. To further probe stationary-phase metabolism, we used quantitative
      metabolomics to investigate possible small-molecule signals that may regulate the
      metabolic rate of E. coli and initiate sporulation in B. subtilis. We hypothesize
      a role for phosphoenolpyruvate (PEP) in regulating E. coli glucose uptake and for
      the redox cofactors NAD(H) and NADP(H) in initiation of sporulation. Our work is
      directly relevant to synthetic biology and metabolic engineering, where active
      metabolism during stationary phase, which uncouples production from growth,
      remains an elusive goal. 

PMID- 24584251
TI  - Establishment of intestinal microbiota during early life: a longitudinal,
      explorative study of a large cohort of Danish infants.
AB  - Fecal samples were obtained from a cohort of 330 healthy Danish infants at 9, 18,
      and 36 months after birth, enabling characterization of interbacterial
      relationships by use of quantitative PCR targeting 31 selected bacterial 16S rRNA
      gene targets representing different phylogenetic levels. Nutritional parameters
      and measures of growth and body composition were determined and investigated in
      relation to the observed development in microbiota composition. We found that
      significant changes in the gut microbiota occurred, particularly from age 9 to 18
      months, when cessation of breastfeeding and introduction of a complementary
      feeding induce replacement of a microbiota characterized by lactobacilli,
      bifidobacteria, and Enterobacteriaceae with a microbiota dominated by Clostridium
      spp. and Bacteroides spp. Classification of samples by a proxy enterotype based
      on the relative levels of Bacteroides spp. and Prevotella spp. showed that
      enterotype establishment occurs between 9 and 36 months. Thirty percent of the
      individuals shifted enterotype between 18 and 36 months. The composition of the
      microbiota was most pronouncedly influenced by the time of cessation of
      breastfeeding. From 9 to 18 months, a positive correlation was observed between
      the increase in body mass index and the increase of the short-chain-fatty-acid
      producing clostridia, the Clostridum leptum group, and Eubacterium hallii.
      Considering previously established positive associations between rapid infant
      weight gain, early breastfeeding discontinuation, and later-life obesity, the
      corresponding microbial findings seen here warrant attention. 

PMID- 24584252
TI  - Enhanced control of cucumber wilt disease by Bacillus amyloliquefaciens SQR9 by
      altering the regulation of Its DegU phosphorylation.
AB  - Bacillus amyloliquefaciens strain SQR9, isolated from the cucumber rhizosphere,
      suppresses the growth of Fusarium oxysporum in the cucumber rhizosphere and
      protects the host plant from pathogen invasion through efficient root
      colonization. In the Gram-positive bacterium Bacillus, the response regulator
      DegU regulates genetic competence, swarming motility, biofilm formation, complex
      colony architecture, and protease production. In this study, we report that
      stepwise phosphorylation of DegU in B. amyloliquefaciens SQR9 can influence
      biocontrol activity by coordinating multicellular behavior and regulating the
      synthesis of antibiotics. Results from in vitro and in situ experiments and
      quantitative PCR (qPCR) studies demonstrate the following: (i) that the lowest
      level of phosphorylated DegU (DegU~P) (the degQ mutation) impairs complex colony
      architecture, biofilm formation, colonization activities, and biocontrol
      efficiency of Fusarium wilt disease but increases the production of macrolactin
      and bacillaene, and (ii) that increasing the level of DegU~P by degQ and degSU
      overexpression significantly improves complex colony architecture, biofilm
      formation, colonization activities, production of the antibiotics bacillomycin D
      and difficidin, and efficiency of biocontrol of Fusarium wilt disease. The
      results offer a new strategy to enhance the biocontrol efficacy of Bacillus
      amyloliquefaciens SQR9. 

PMID- 24584253
TI  - Top-down proteomic identification of Shiga toxin 2 subtypes from Shiga toxin
      producing Escherichia coli by matrix-assisted laser desorption ionization-tandem
      time of flight mass spectrometry.
AB  - We have analyzed 26 Shiga toxin-producing Escherichia coli (STEC) strains for
      Shiga toxin 2 (Stx2) production using matrix-assisted laser desorption ionization
      (MALDI)-tandem time of flight (TOF-TOF) tandem mass spectrometry (MS/MS) and top
      down proteomic analysis. STEC strains were induced to overexpress Stx2 by
      overnight culturing on solid agar supplemented with either ciprofloxacin or
      mitomycin C. Harvested cells were lysed by bead beating, and unfractionated
      bacterial cell lysates were ionized by MALDI. The A2 fragment of the A subunit
      and the mature B subunit of Stx2 were analyzed by MS/MS. Sequence-specific
      fragment ions were used to identify amino acid subtypes of Stx2 using top-down
      proteomic analysis using software developed in-house at the U.S. Department of
      Agriculture (USDA). Stx2 subtypes (a, c, d, f, and g) were identified on the
      basis of the mass of the A2 fragment and the B subunit as well as from their
      sequence-specific fragment ions by MS/MS (postsource decay). Top-down proteomic
      identification was in agreement with DNA sequencing of the full Stx2 operon
      (stx2) for all strains. Top-down results were also compared to a bioassay using a
      Vero-d2EGFP cell line. Our results suggest that top-down proteomic identification
      is a rapid, highly specific technique for distinguishing Stx2 subtypes. 

PMID- 24584254
TI  - The iron stimulon and fur regulon of Geobacter sulfurreducens and their role in
      energy metabolism.
AB  - Iron plays a critical role in the physiology of Geobacter species. It serves as
      both an essential component for proteins and cofactors and an electron acceptor
      during anaerobic respiration. Here, we investigated the iron stimulon and ferric
      uptake regulator (Fur) regulon of Geobacter sulfurreducens to examine the
      coordination between uptake of Fe(II) and the reduction of Fe(III) at the
      transcriptional level. Gene expression studies across a variety of different iron
      concentrations in both the wild type and a Deltafur mutant strain were used to
      determine the iron stimulon. The stimulon consists of a broad range of gene
      products, ranging from iron-utilizing to central metabolism and iron reduction
      proteins. Integration of gene expression and chromatin immunoprecipitation (ChIP)
      data sets assisted in the identification of the Fur transcriptional regulatory
      network and Fur's role as a regulator of the iron stimulon. Additional
      physiological and transcriptional analyses of G. sulfurreducens grown with
      various Fe(II) concentrations revealed the depth of Fur's involvement in energy
      metabolism and the existence of redundancy within the iron-regulatory network
      represented by IdeR, an alternative iron transcriptional regulator. These
      characteristics enable G. sulfurreducens to thrive in environments with
      fluctuating iron concentrations by providing it with a robust mechanism to
      maintain tight and deliberate control over intracellular iron homeostasis. 

PMID- 24584256
TI  - Dedication special issue: the Copenhagen Aging and Midlife Biobank--in honor of
      Dr. Kirsten Avlund, director.

PMID- 24584255
TI  - Adaptation of the wine bacterium Oenococcus oeni to ethanol stress: role of the
      small heat shock protein Lo18 in membrane integrity.
AB  - Malolactic fermentation in wine is often carried out by Oenococcus oeni. Wine is
      a stressful environment for bacteria because ethanol is a toxic compound that
      impairs the integrity of bacterial membranes. The small heat shock protein (sHsp)
      Lo18 is an essential actor of the stress response in O. oeni. Lo18 prevents the
      thermal aggregation of proteins and plays a crucial role in membrane quality
      control. Here, we investigated the interaction between Lo18 and four types of
      liposomes: one was prepared from O. oeni grown under optimal growth conditions
      (here, control liposomes), one was prepared from O. oeni grown in the presence of
      8% ethanol (here, ethanol liposomes), one was prepared from synthetic
      phospholipids, and one was prepared from phospholipids from Bacillus subtilis or
      Lactococcus lactis. We observed the strongest interaction between Lo18 and
      control liposomes. The lipid binding activity of Lo18 required the dissociation
      of oligomeric structures into dimers. Protein protection experiments carried out
      in the presence of the liposomes from O. oeni suggested that Lo18 had a higher
      affinity for control liposomes than for a model protein. In anisotropy
      experiments, we mimicked ethanol action by temperature-dependent fluidization of
      the liposomes. Results suggest that the principal determinant of Lo18-membrane
      interaction is lipid bilayer phase behavior rather than phospholipid composition.
      We suggest a model to describe the ethanol adaptation of O. oeni. This model
      highlights the dual role of Lo18 in the protection of proteins from aggregation
      and membrane stabilization and suggests how modifications of phospholipid content
      may be a key factor determining the balance between these two functions. 

PMID- 24584257
TI  - Copenhagen Aging and Midlife Biobank (CAMB): an introduction.

PMID- 24584258
TI  - Personality in late midlife: associations with demographic factors and cognitive
      ability.
AB  - OBJECTIVES: To analyze associations in late midlife between sex, age, education
      and social class, and the Big Five personality traits; to analyze associations
      between personality traits and cognitive ability in late midlife; and to evaluate
      how these associations are influenced by demographic factors. METHODS: The study
      sample comprised 5,397 late midlife participants from three cohorts who had
      completed the NEO Five-Factor Inventory (NEO-FFI) and a measure of cognitive
      ability. RESULTS: Associations were demonstrated between the five NEO-FFI
      personality traits, and all included demographic factors. Cognitive ability and
      years of education correlated with several NEO-FFI personality traits in analyses
      adjusting for demographic variables. Cohort differences were observed for
      Extraversion and Openness. DISCUSSION: Robust sex, educational, and social class
      differences in personality may contribute to late midlife social gradients in
      health and early aging. Demographic factors did not fully explain correlations
      between personality and cognitive ability or cohort differences in personality.

PMID- 24584259
TI  - The relationship between cognitive ability and demographic factors in late
      midlife.
AB  - OBJECTIVE: The aim of the article is to analyze associations between sex, age,
      education, and social class and cognitive ability in late midlife and to evaluate
      differences in cognitive ability among the three Copenhagen Aging and Midlife
      Biobank (CAMB) cohorts. METHOD: The sample comprised 5,417 CAMB participants from
      three cohorts with scores on the Intelligenz-Struktur-Test 2000 R (I-S-T 2000 R).
      RESULTS: Independent associations of cognitive ability with age, sex, education,
      and occupational social class were observed. Particularly, strong associations
      with cognitive ability were obtained for school education, and consistent sex
      differences were observed with higher cognitive ability in men. Differences in
      cognitive ability among the three cohorts were small and primarily reflected
      demographic differences. DISCUSSION: Late-midlife cognitive ability is associated
      with a number of demographic factors, and demographic differences may contribute
      to individual differences in health and early aging. In analyses of cognitive
      ability, the three CAMB cohorts can be combined provided the relevant demographic
      variables are included as covariates.

PMID- 24584260
TI  - Smoking and drinking as risk indicators for tooth loss in middle-aged Danes.
AB  - OBJECTIVES: To investigate tobacco and alcohol consumption as risk indicators for
      missing teeth in late middle-aged Danes. METHOD: In all, 1,517 Copenhagen Aging
      and Midlife Biobank (CAMB) participants received a clinical oral examination that
      included number of teeth. Information on smoking, drinking, and various
      covariates was obtained using self-administered, structured questionnaires.
      Descriptive statistics and logistic regression (dependent variable: 6+ vs. <6
      missing teeth) were used to investigate smoking and drinking in relation to
      missing teeth. RESULTS: Current smokers, persons who currently or previously
      smoked >15 tobacco units/day, and persons who had smoked for 27+ years had
      elevated mean scores of missing teeth and associated odds ratios (OR) compared
      with never smokers. Relative to nondrinkers, alcohol consumption was associated
      with reduced odds of missing 6+ teeth. DISCUSSION: Our findings suggest that
      smoking is positively associated, while alcoholic beverage consumption is
      inversely related to tooth loss in middle-aged Danes.

PMID- 24584261
TI  - Social gradient in allostatic load among Danish men and women in late midlife.
AB  - OBJECTIVE: The objective of the present study is to describe the prevalence of
      allostatic load (AL) among Danish men and women in late midlife, and if there is
      a social gradient in AL. METHOD: A total of 5,420 participants from the
      Copenhagen Aging and Midlife Biobank (CAMB) aged 48 to 63 years (68.5% men, 31.5%
      women) underwent a health examination including standardized measures of height,
      weight, body fat, and blood pressure in 2009-2011. AL (range 0-14) was
      established by summing the scores of the poorest quartile for each of 14
      biological variables related to the metabolic and immune systems. RESULTS: We
      found a social gradient in AL in late midlife among men and women living in
      Denmark. DISCUSSION: AL may be a potential biomarker for early aging in countries
      with a strong social welfare system. It is important for intervention studies to
      be aware of this type of biological vulnerability already present in late
      midlife.

PMID- 24584262
TI  - Social class differences in physical functions in middle-aged men and women.
AB  - OBJECTIVE: The objective of the present study is to analyze gender differences
      and social class gradients in physical functions; and to study whether the social
      class gradients in physical functions in midlife differed between men and women.
      METHOD: This study used traditionally used physical performance tests and we
      added several tests of vigorous physical functioning (trunk muscle strength and
      power and sagittal flexibility). We measured reaction time, one-legged balance,
      sagittal flexibility, jump height, chair rise ability, trunk muscle- and handgrip
      strength in 5,412 participants aged 50 to 60 years (68.5% men). RESULTS: We found
      gender differences and social class gradients for all physical performance tests.
      We did not find an interaction between social class and gender, indicating that
      the social gradient in physical functions did not differ between men and women.
      DISCUSSION: Including measures of vigorous physical functioning may add to the
      existing knowledge on development of functional limitation and poorer functional
      health later in life.

PMID- 24584263
TI  - Addressing social inequality in aging by the Danish occupational social class
      measurement.
AB  - OBJECTIVE: To present the Danish Occupational Social Class (DOSC) measurement as
      a measure of socioeconomic position (SEP) applicable in a late midlife
      population, and to analyze associations of this measure with three aging-related
      outcomes in midlife, adjusting for education. METHOD: Systematic coding
      procedures of the DOSC measurement were applied to 7,084 participants from the
      Copenhagen Aging and Midlife Biobank (CAMB) survey. We examined the association
      of this measure of SEP with chronic conditions, self-rated health, and mobility
      in logistic regression analyses, adjusting for school education in the final
      analysis. RESULTS: The measure of SEP showed a strong social gradient along the
      social classes in terms of prevalence of chronic conditions, poor self-rated
      health, and mobility limitations. Adjusting for school education attenuated the
      association only to a minor degree. DISCUSSION: The DOSC measure was associated
      with aging-related outcomes in a midlife Danish population, and is, thus, well
      suited for future epidemiological research on social inequalities in health and
      aging.

PMID- 24584264
TI  - Content validity and reliability of the Copenhagen social relations
      questionnaire.
AB  - OBJECTIVE: The aim of the present article is to describe the face and content
      validity as well as reliability of the Copenhagen Social Relations Questionnaire
      (CSRQ). METHOD: The face and content validity test was based on focus group
      discussions and individual interviews with 31 informants. Another 94 men and
      women participated in an 8-day test-retest analysis. RESULTS: Informants
      generally expressed that the questions and response categories were relevant and
      easy to understand. Themes on structure of social relations, social support, and
      negative aspects of social relations emerged clearly from the interviews. Two
      additional themes not covered by CSRQ on dynamics and reciprocity of social
      relations were identified. DISCUSSION: CSRQ holds satisfactory face and content
      validity as well as reliability, and is suitable for measuring structure and
      function of social relations including the negative aspects among middle-aged
      individuals.

PMID- 24584265
TI  - Electrophilic alkynylation of ketones using hypervalent iodine.
AB  - A new method for the electrophilic alpha-alkynylation of ketones was developed
      using hypervalent iodine under mild and metal-free conditions. Carbonyl compounds
      containing an alpha-acetylene group were obtained in good to excellent yields for
      several ketones using 1-[(trimethylsilyl)ethynyl]-1,2-benziodoxol-3(1H)-one (TMS
      EBX) as an alkynylation agent in the presence of t-BuOK and TBAF in THF as
      solvent. Under the same conditions, an aldehyde was alkynylated. 

PMID- 24584266
TI  - Magnetic resonance imaging-directed biopsy improves the prediction of prostate
      cancer aggressiveness compared with a 12-core transrectal ultrasound-guided
      prostate biopsy.
AB  - The Gleason grading system is a fundamental indicator of the aggressive nature of
      prostate cancer (PCa). Diffusion-weighted imaging (DWI) and magnetic resonance
      (MR) spectroscopy (MRS) are methods for the assessment of PCa aggressiveness. The
      present study was designed to prospectively investigate whether transrectal
      ultrasound (TRUS)-guided MR imaging (MRI)-directed biopsies (TRUS-MR-Dbs) improve
      the prediction of PCa aggressiveness in comparison with 12-core TRUS-guided
      biopsies (TRUS-Gbs). A total of 518 patients underwent pre-biopsy multi
      parametric MRI to identify the clinically suspicious PCa regions. TRUS-MR-Dbs
      were performed on patients with suspected PCa by MRI in addition to TRUS-Gbs.
      Only patients who underwent radical prostatectomy (RP) were included in the
      comparative analysis. TRUS-biopsy was directed to those areas within suspicious
      regions with a minimum apparent diffusion coefficient obtained by DWI or with a
      maximum (choline + creatine)/citrate ratio obtained by MRS. The highest Gleason
      grades (HGGs) and the Gleason scores (GSs) of specimens were identified. The
      biopsies and RP results were evaluated using a McNemar test or chi2 analyses
      using Fisher' exact tests. MRI results were positive in 254 (49.0%) of the 518
      patients. TRUS-MR-Db detected 165/254 (65.0%) cancer cases and TRUS-Gb detected
      190/518 (36.7%) cancer cases. Forty patients underwent RP. The TRUS-MR-Dbs method
      demonstrated a higher concordance rate (CR) with RP (89.6%) than TRUS-Gbs (72.9%,
      P=0.008) for the overall HGG. The CRs with RP for TRUS-MR-Dbs vs. those for TRUS
      Gbs were 100 vs. 85.7% (P=0.5), 87.5 vs. 68.8% (P=0.031) and 50 vs. 50% (P=1) for
      HGG3, HGG4 and HGG5, respectively. The HGG CRs with RP for DWI-directed biopsies
      (DWI-Dbs) vs. MRS-directed biopsies (MRS-Dbs) were 77.1 vs. 50.0% (P=0.015) for
      the overall tumors, 80.0 vs. 40.0% (P=0.003) for peripheral zone tumors and 69.2
      vs. 76.9% (P=1) for transition zone tumors. A total of 37 (77.1%) and 25 (52.1%;
      P=0.007) tumors were assigned accurate GS for TRUS-MR-Dbs and TRUS-Gbs,
      respectively. The results revealed that TRUS-MR-Dbs improved the prediction of
      PCa aggressiveness and that DWI-Dbs had a superior performance when compared with
      MRS-Dbs in the peripheral zone.

PMID- 24584267
TI  - Comparison of the metal concentrations in organs of two bird species from western
      of Iran.
AB  - This study was conducted to measure the concentration of several elements (Cd,
      Pb, Cu, and Zn) in organs of Coot, Fulica atra, and Mallard, Anas platyrhynchos,
      in order to: (1) determine the significant between metal concentrations in
      different organs (kidney, liver, pectoral muscle, and feather), (2) to evaluate
      species differences in metal exposure and accumulation, and (3) to study gender
      related trends in metal accumulation. The metal concentrations in organs of F.
      atra and A. platyrhynchos decreased in the following order: Zn > Cu > Pb > Cd.
      These results revealed that there were no significant differences between males
      and females except for Cu in liver and feather, and Pb in kidney.

PMID- 24584268
TI  - Effects of glyphosate on growth rate, metabolic rate and energy reserves of early
      juvenile crayfish, Cherax quadricarinatus M.
AB  - Early juveniles of the crayfish Cherax quadricarinatus were exposed for 60 days
      to 10 and 40 mg/L of pure glyphosate (acid form) in freshwater. Mortality was 33
      % at the highest concentration, while no differences in molting were noted among
      treatments. After the first month of exposure, weight gain was significantly (p <
      0.05) reduced in the 40 mg/L group. At the end of the assay, lipid levels in
      muscle, as well as protein level in both hepatopancreas and muscle were
      significantly (p < 0.05) reduced. These results suggest long-term utilization of
      both lipid and protein as main energetic reserves, likely in response to the
      chronic stress associated with herbicide exposure. Besides, the lower pyruvate
      kinase activity in muscle suggests a possible metabolic depression in this
      tissue. The hemolymphatic ASAT:ALAT ratio showed higher levels than the control
      at the highest glyphosate concentration, indicating possible damage to several
      tissues.

PMID- 24584269
TI  - Double-balloon endoscopy: an effective rescue procedure after incomplete
      conventional colonoscopy.
AB  - OBJECTIVE: A significant percentage of colonoscopies remain incomplete because of
      a failure to intubate the caecum. By double-balloon endoscopy (DBE), originally
      developed for deep enteroscopy, an otherwise incomplete examination of the colon
      might be completed. We evaluated the success rate of caecal intubation, the
      reasons for its failure and the therapeutic consequences of using DBE after
      incomplete conventional colonoscopy. METHODS: We report our single-centre
      experience of using DBE to complete an otherwise incomplete colonoscopy. A total
      of 114 consecutive patients, 45 male and 69 female, with a mean age of 64.8
      years, who had undergone 116 procedures, were evaluated retrospectively by a
      review of their medical records. RESULTS: The main causes for failed caecal
      intubation using a conventional colonoscope were loop formation in 70 patients
      (61.4%) and an adhesive angulated sigmoid in 33 (28.9%). Caecal intubation by DBE
      was successful in 101 patients (88.6%). The rate of failure was not associated
      with the cause of failure of the previous colonoscopy. In 55 patients (48.2%) a
      relevant new diagnosis was made in the previously inaccessible part of the colon:
      carcinoma (n=4; 3.5%), one or more adenomas (n=48; 42.1%) and caecal flat
      hyperplastic polyps (n=4; 3.5%). Endoscopic polypectomy was performed in 51
      patients (44.7%); two complications occurred, both being mild postpolypectomy
      bleedings. In seven patients (6.1%) a subsequent surgical resection was
      performed. CONCLUSION: Colonoscopy by DBE was useful in most patients in whom
      conventional colonoscopy was incomplete, irrespective of the cause of the
      failure. In nearly half the patients, a relevant new diagnosis was made with
      therapeutic consequences.

PMID- 24584270
TI  - Molecular and immunohistochemical profile of a basaloid (cloacogenic) carcinoma
      of the sigmoid colon: possible predictive value for clinical outcomes.
AB  - A 61-year-old woman was hospitalized with a 5-week history of abdominal
      discomfort, change in bowel habits, and weight loss. Colonoscopy showed a
      protruded tumor of the sigmoid colon first diagnosed as undifferentiated
      carcinoma. Surgical resection of the sigmoid colon was performed. Histological
      examination of the surgical specimen showed a proliferation of basaloid cells
      arranged in tumor clusters with central comedonecrosis and peripheral palisading
      of the nuclei. The tumor invaded the subserosa and presented liver metastasis
      without lymph node metastases. The tumor cells were marked by keratin AE1/AE3,
      keratin 5/6, epithelial membrane antigen, bcl-2, vascular endothelial growth
      factor, CD105, neuron-specific enolase, MLH-1, MSH-2, and p53, and were negative
      for keratin 7/20, chromogranin, synaptophysin, carcinoembryonic antigen, p63, c
      KIT, and maspin. A high p53 nuclear index was also detected. On the basis of
      these characteristics and molecular examinations, the final diagnosis was
      microsatellite stable/human papilloma virus-negative/K-ras mutated/BRAF wild-type
      basaloid carcinoma (BC). Only seven BCs of the colon were reported in the
      literature, this being the eighth one and the first case that reports new
      molecular findings about microsatellite instability, K-ras/BRAF mutations,
      angiogenesis, and maspin expression in BC, with direct involvement in targeted
      therapy.

PMID- 24584271
TI  - Intestinal lesions in pediatric Crohn disease: comparative detectability among
      pulse sequences at MR enterography.
AB  - BACKGROUND: Variable sequences can be used in MR enterography, and no consensus
      exists for the best protocol in children with Crohn disease. OBJECTIVE: To
      compare the lesion detectability of various MR enterography sequences and to
      correlate the findings of these sequences with the Pediatric Crohn's Disease
      Activity Index (PCDAI) in children with Crohn disease. MATERIALS AND METHODS:
      Children with clinically or pathologically confirmed Crohn disease underwent MR
      enterography, including a single-shot fast spin-echo (SSFSE) sequence, motility
      imaging (coronal 2-D balanced fast field echo), diffusion-weighted imaging (DWI),
      and dynamic contrast enhancement imaging (including arterial, portal and delayed
      phases). The lesion detectability of each sequence was graded 0-2 for each
      involved bowel segment. The lesion detectability and PCDAI result on different
      sequences were compared using the weighted least squares method and Student's t
      test, respectively. RESULTS: Fifteen children (11 boys, 4 girls, mean age 13.7 +/
      1.4 years) with a total of 41 lesions were included in this study. All lesions
      detected in more than two sequences were visible on the single-shot fast spin
      echo (SSFSE) sequence. The relative lesion detection rate was 78.1% on motility
      imaging, 90.2% on DWI, and 92.7% on arterial, 95.1% on portal and 95.1% on
      delayed phase imaging. Compared to the SSFSE sequence, motility imaging (P <
      0.001) and DWI (P = 0.039) demonstrated lower detectability. The mean PCDAI
      result in the detected lesions was statistically higher only on dynamic
      enhancement imaging (P < 0.001). CONCLUSION: All MR enterography sequences were
      found to have relatively high lesion detectability in children with Crohn
      disease, while motility imaging showed the lowest lesion detectability. Lesions
      detected on dynamic enhancement imaging showed a higher PCDAI result, which
      suggests that this sequence is specific for active inflammation.

PMID- 24584272
TI  - Three-dimensional manipulation with scanning near-field optical nanotweezers.
AB  - Recent advances in nanotechnologies have prompted the need for tools to
      accurately and non-invasively manipulate individual nano-objects. Among the
      possible strategies, optical forces have been predicted to provide researchers
      with nano-optical tweezers capable of trapping a specimen and moving it in three
      dimensions. In practice, however, the combination of weak optical forces and
      photothermal issues has thus far prevented their experimental realization. Here,
      we demonstrate the first three-dimensional optical manipulation of single 50 nm
      dielectric objects with near-field nanotweezers. The nano-optical trap is built
      by engineering a bowtie plasmonic aperture at the extremity of a tapered metal
      coated optical fibre. Both the trapping operation and monitoring are performed
      through the optical fibre, making these nanotweezers totally autonomous and free
      of bulky optical elements. The achieved trapping performances allow for the
      trapped specimen to be moved over tens of micrometres over a period of several
      minutes with very low in-trap intensities. This non-invasive approach is foreseen
      to open new horizons in nanosciences by offering an unprecedented level of
      control of nanosized objects, including heat-sensitive biospecimens. 

PMID- 24584273
TI  - Nanomechanical sensors: Measuring a response in blood.

PMID- 24584274
TI  - Black phosphorus field-effect transistors.
AB  - Two-dimensional crystals have emerged as a class of materials that may impact
      future electronic technologies. Experimentally identifying and characterizing new
      functional two-dimensional materials is challenging, but also potentially
      rewarding. Here, we fabricate field-effect transistors based on few-layer black
      phosphorus crystals with thickness down to a few nanometres. Reliable transistor
      performance is achieved at room temperature in samples thinner than 7.5 nm, with
      drain current modulation on the order of 10(5) and well-developed current
      saturation in the I-V characteristics. The charge-carrier mobility is found to be
      thickness-dependent, with the highest values up to ~ 1,000 cm(2) V(-1) s(-1)
      obtained for a thickness of ~ 10 nm. Our results demonstrate the potential of
      black phosphorus thin crystals as a new two-dimensional material for applications
      in nanoelectronic devices.

PMID- 24584275
TI  - An antidamping spin-orbit torque originating from the Berry curvature.
AB  - Magnetization switching at the interface between ferromagnetic and paramagnetic
      metals, controlled by current-induced torques, could be exploited in magnetic
      memory technologies. Compelling questions arise regarding the role played in the
      switching by the spin Hall effect in the paramagnet and by the spin-orbit torque
      originating from the broken inversion symmetry at the interface. Of particular
      importance are the antidamping components of these current-induced torques acting
      against the equilibrium-restoring Gilbert damping of the magnetization dynamics.
      Here, we report the observation of an antidamping spin-orbit torque that stems
      from the Berry curvature, in analogy to the origin of the intrinsic spin Hall
      effect. We chose the ferromagnetic semiconductor (Ga,Mn)As as a material system
      because its crystal inversion asymmetry allows us to measure bare ferromagnetic
      films, rather than ferromagnetic-paramagnetic heterostructures, eliminating by
      design any spin Hall effect contribution. We provide an intuitive picture of the
      Berry curvature origin of this antidamping spin-orbit torque as well as its
      microscopic modelling. We expect the Berry curvature spin-orbit torque to be of
      comparable strength to the spin-Hall-effect-driven antidamping torque in
      ferromagnets interfaced with paramagnets with strong intrinsic spin Hall effect. 

PMID- 24584276
TI  - Surface-stress sensors for rapid and ultrasensitive detection of active free
      drugs in human serum.
AB  - There is a growing appreciation that mechanical signals can be as important as
      chemical and electrical signals in biology. To include such signals in a systems
      biology description for understanding pathobiology and developing therapies,
      quantitative experiments on how solution-phase and surface chemistry together
      produce biologically relevant mechanical signals are needed. Because of the
      appearance of drug-resistant hospital 'superbugs', there is currently great
      interest in the destruction of bacteria by bound drug-target complexes that
      stress bacterial cell membranes. Here, we use nanomechanical cantilevers as
      surface-stress sensors, together with equilibrium theory, to describe
      quantitatively the mechanical response of a surface receptor to different
      antibiotics in the presence of competing ligands in solution. The antibiotics
      examined are the standard, Food and Drug Administration-approved drug of last
      resort, vancomycin, and the yet-to-be approved oritavancin, which shows promise
      for controlling vancomycin-resistant infections. The work reveals variations
      among strong and weak competing ligands, such as proteins in human serum, that
      determine dosages in drug therapies. The findings further enhance our
      understanding of the biophysical mode of action of the antibiotics and will help
      develop better treatments, including choice of drugs as well as dosages, against
      pathogens. 

PMID- 24584277
TI  - Prevention of colonic spasm using L-menthol in colonoscopic examination.
AB  - PURPOSE: The detailed efficacy of intraluminal L-menthol for preventing colonic
      spasm is not known. The aim of this study was to evaluate the effectiveness of L
      menthol in preventing colonic spasm during colonoscopy. METHODS: We analyzed 65
      patients (mean age: 71.7 years; 49 men and 16 women) who were administered 0.8% L
      menthol (MINCLEA, Nihon Seiyaku, Tokyo, Japan) intraluminally for severe colonic
      spasm during colonoscopic examination at Kyoto Prefectural University of Medicine
      between February 2012 and May 2013. The efficacy of L-menthol was defined as the
      absence of colonic spasm during a period of 30 s, and its effect was evaluated at
      30 s, 1 min, and 5 min after administration. Additionally, various
      characteristics of these patients were analyzed. Twenty-seven patients with
      severe colonic spasm were administered intraluminal water and assessed as
      controls. RESULTS: L-Menthol was effective in preventing colonic spasms in 60.0%,
      70.8%, and 46.5% of patients at 30 s, 1 min, and 5 min, respectively. In
      contrast, water was effective in 22.2%, 29.6%, and 48.1% of patients at 30 s, 1
      min, and 5 min, respectively. There was a significant difference about the
      efficacy at 30 s and 1 min between L-menthol and water (P = 0.0009, P = 0.0006).
      CONCLUSIONS: L-Menthol (0.8%) was effective in preventing colonic spasm during
      colonoscopic examination.

PMID- 24584278
TI  - Postoperative hemoglobin levels and their association with myocardial ischemia in
      non-cardiac surgical patients.

PMID- 24584279
TI  - Progressively unstable c2 spondylolysis requiring spinal fusion: case report.
AB  - Cervical spondylolysis is a rare condition defined as a corticated cleft at the
      pars interarticularis in the cervical spine. This is the case of C2 spondylolysis
      demonstrating progressive significant instability, which was successfully treated
      by anterior cervical discectomy and fusion (ACDF) with cervical anterior plate.
      We describe a 20-year-old female with C2 spondylolysis presenting with
      progressive worsening of neck pain associated with progressive instability at the
      C2/3 segment. The progression of instability was well-documented on flexion
      extension cervical spine x-rays. She was successfully treated by C2/3 ACDF with
      anterior cervical plate. Her preoperative significant neck pain resolved
      immediately after the surgical intervention. She was completely free from
      neurological symptoms at 1-year postoperative follow-up. We also review the
      literature and discuss 24 reported cases with C2 spondylolysis. When planning
      treatment, we should make sure to differentiate this pathology from acute
      traumatic fracture, which is a hangman's fracture. Assessment of C2/3 instability
      associated with neurological deficits is extremely important to consider
      management properly. C2/3 ACDF with cervical plate is biomechanically viable,
      less invasive, and provides adequate surgical stabilization for unstable C2
      spondylolysis. 

PMID- 24584280
TI  - Efficacy of superficial temporal artery-middle cerebral artery double anastomoses
      in a patient with rapidly progressive moyamoya disease: case report.
AB  - Moyamoya disease can be associated with a rapidly progressive course in young
      patients. This report describes a patient with moyamoya disease who experienced
      rapid disease progression, resulting in cerebral infarction and a wide area of
      diminished cerebral perfusion. Double superficial temporal artery (STA)-middle
      cerebral artery (MCA) anastomoses were utilized to immediately increase cerebral
      perfusion in the affected area. This case involved a 5-year-old girl who had been
      diagnosed with moyamoya disease and had undergone STA-MCA anastomosis with
      indirect bypass in the right hemisphere at the age of 3. At the time of
      presentation, magnetic resonance (MR) imaging showed cerebral infarction at the
      left frontal lobe, and MR angiography showed rapidly progressive narrowing of the
      left MCA that had not been present 3 months prior. N-isopropyl-p-[I123]
      iodoamphetamine single-photon emission computed tomography (IMP-SPECT) showed
      markedly decreased uptake in the left hemisphere. She underwent emergent STA-MCA
      double anastomoses with indirect bypass on the left side. IMP-SPECT showed marked
      increase in uptake in the left hemisphere. The anterior cerebral artery (ACA)
      territory adjacent to the cerebral infarction also showed increased uptake on the
      SPECT. Postoperatively, there were no clinical or radiographic indications of
      ischemic or hemorrhagic complications. Double anastomoses are effective in
      quickly and significantly increasing blood flow. The postoperative course in this
      case was uneventful. Double anastomoses are a surgical option for patients with
      moyamoya disease who show rapid disease progression, even in those in the acute
      phase of cerebral infarction. 

PMID- 24584281
TI  - Functional plasticity of language confirmed with intraoperative electrical
      stimulations and updated neuronavigation: case report of low-grade glioma of the
      left inferior frontal gyrus.
AB  - Removal of glioma from the dominant side of the inferior frontal gyrus (IFG) is
      associated with a risk of permanent language dysfunction. While intraoperative
      cortical and subcortical electrical stimulations can be used for functional
      language mapping in an effort to reduce the risk of postoperative neurological
      impairment, the extent of resection is limited by the functional boundaries.
      Recent reports proposed that a two-stage surgical approach for low-grade glioma
      in eloquent areas could avoid permanent deficits via the functional plasticity
      that occurs between the two operations. The report describes a patient with World
      Health Organization (WHO) grade II oligoastrocytoma in the left IFG, in
      functional plasticity of language occurred in the interval between two
      consecutive surgeries. Intraoperative electrical stimulations suggested that a
      language area and related subcortical fiber crossed the pre-central sulcus during
      tumor progression owing to functional plasticity. In the present case, we
      integrated neurophysiological data into the intraoperative neuronavigation
      system. We also confirmed the peri-lesional shift of language area and related
      subcortical fiber on image findings. Consequently, the tumor was sub-totally
      removed with two separate resections. Permanent language disturbance did not
      occur, and this favorable outcome was attributed to functional plasticity. The
      present experience sustains the multistage approach for low-grade gliomas in the
      language area. A combination of intraoperative electrical stimulations and
      updated neuronavigation may facilitate the characterization of brain functional
      plasticity. 

PMID- 24584282
TI  - Mechanism of antibacterial activity of copper nanoparticles.
AB  - In a previous communication, we reported a new method of synthesis of stable
      metallic copper nanoparticles (Cu-NPs), which had high potency for bacterial cell
      filamentation and cell killing. The present study deals with the mechanism of
      filament formation and antibacterial roles of Cu-NPs in E. coli cells. Our
      results demonstrate that NP-mediated dissipation of cell membrane potential was
      the probable reason for the formation of cell filaments. On the other hand, Cu
      NPs were found to cause multiple toxic effects such as generation of reactive
      oxygen species, lipid peroxidation, protein oxidation and DNA degradation in E.
      coli cells. In vitro interaction between plasmid pUC19 DNA and Cu-NPs showed that
      the degradation of DNA was highly inhibited in the presence of the divalent metal
      ion chelator EDTA, which indicated a positive role of Cu(2+) ions in the
      degradation process. Moreover, the fast destabilization, i.e. the reduction in
      size, of NPs in the presence of EDTA led us to propose that the nascent Cu ions
      liberated from the NP surface were responsible for higher reactivity of the Cu
      NPs than the equivalent amount of its precursor CuCl2; the nascent ions were
      generated from the oxidation of metallic NPs when they were in the vicinity of
      agents, namely cells, biomolecules or medium components, to be reduced
      simultaneously.

PMID- 24584283
TI  - Consumption of Ocimum sanctum L. and Citrus paradisi infusions modulates lipid
      metabolism and insulin resistance in obese rats.
AB  - A high saturated fat and fructose diet leads to metabolic disorders through
      dysregulation of genes involved in lipid metabolism. Consumption of plant
      infusions reduces these obesity alterations, but the precise mechanism remains
      unclear. In this study, we investigated the effect and the possible mechanism of
      Ocimum sanctum L. (OS) and Citrus paradisi (CP) infusions in diet-induced obese
      rats. CP and OS infusions suppressed hepatic tissue fat accumulation, and
      significantly down-regulated the mRNA levels of two hepatic lipogenesis genes:
      sterol regulatory element binding protein 1c (SREBP1c) and fatty acid synthase
      (FAS) compared with the obese control. Treatment with these infusions up
      regulated the hepatic expression of mRNA related to mitochondrial fatty acid
      uptake: peroxisome proliferator activated receptor alpha (PPARalpha) and the
      expression of carnitine palmitoyl-transferase 1a (CPT1a). Both infusions improved
      insulin resistance, with OS showing the major effect. Consumption of these
      infusions reduces the damage caused by free radicals, protecting hepatic lipids
      and proteins. Additionally, plant infusions increase activity of hepatic enzymes:
      glutathione S-transferase (GST), glutathione peroxidase (GPX), and catalase
      (CAT). Our results suggest that the effects of CP and OS infusions on lipid
      metabolism are related to the down-regulation of genes involved in lipogenesis,
      particularly for OS, and to the increase in lipid beta-oxidation, especially for
      CP infusion. In conclusion, the consumption of these plant infusions is a
      feasible adjuvant therapy for metabolic changes induced by obesity. 

PMID- 24584284
TI  - Biodiversity, photosynthetic mode, and ecosystem services differ between native
      and novel ecosystems.
AB  - Human activities have caused non-native plant species with novel ecological
      interactions to persist on landscapes, and it remains controversial whether these
      species alter multiple aspects of communities and ecosystems. We tested whether
      native and exotic grasslands differ in species diversity, ecosystem services, and
      an important aspect of functional diversity (C3:C4 proportions) by sampling 42
      sites along a latitudinal gradient and conducting a controlled experiment. Exotic
      dominated grasslands had drastically lower plant diversity and slightly higher
      tissue N concentrations and forage quality compared to native-dominated sites.
      Exotic sites were strongly dominated by C4 species at southern and C3 species at
      northern latitudes with a sharp transition at 36-38 degrees , whereas native
      sites contained C3:C4 mixtures. Large differences in C3:C4 proportions and
      temporal niche partitioning were found between native and exotic mixtures in the
      experiment, implying that differences in C3:C4 proportions along the latitudinal
      gradient are caused partially by species themselves. Our results indicate that
      the replacement of native- by exotic-dominated grasslands has created a
      management tradeoff (high diversity versus high levels of certain ecosystem
      services) and that models of global change impacts and C3/C4 distribution should
      consider effects of exotic species. 

PMID- 24584301
TI  - Protective effects of daphnetin on sodium taurocholate-induced severe acute
      pancreatitis in rats.
AB  - Severe acute pancreatitis (SAP) is the sudden onset of pancreatic inflammation,
      which is characterized by edema, acinar cell necrosis, hemorrhage and severe
      inflammation of the pancreas and is associated with a high mortality rate.
      Daphnetin has been shown to alleviate organ injury in a variety of preclinical
      animal models of coagulation disorders. The aim of the present study was to
      investigate the protective effects of daphnetin on severe acute pancreatitis in a
      rat model. Severe acute pancreatitis in the rat model was induced by retrograde
      infusion of 5% sodium taurocholate (1 ml/kg) into the bile-pancreatic duct.
      Daphnetin (4 mg/kg) was administered intraperitoneally at 30 min prior to the
      infusion of sodium taurocholate. The severity of pancreatitis was evaluated by
      various analyses of serum amylase and lipase, tumor necrosis factor-alpha (TNF
      alpha) and interleukin-1beta (IL-1beta) levels, myeloperoxidase (MPO) activity
      and malondialdehyde (MDA) content, as well as by histological grading. The levels
      of TNF-alpha and IL-1beta in the serum were measured by ELISA. The results
      revealed that the daphnetin-treated SAP rat group (SAP-D) exhibited a lower
      pathological score of the pancreas compared with the SAP group (SAP). Further
      analyses demonstrated that the SAP-D group had lower levels of serum amylase,
      lipase and pro-inflammatory cytokines, including TNF-alpha and IL-1beta, and a
      decreased MPO activity and MDA content 3, 6 and 12 h subsequent to the infusion
      of sodium taurocholate compared with the SAP group (SAP). These findings
      indicated that daphnetin exerted a protective function in the SAP rat model.
      Therefore, daphnetin may be considered as a potential compound for the therapy
      and prevention of acute pancreatitis.

PMID- 24584302
TI  - Artificial heme-proteins: determination of axial ligand orientations through
      paramagnetic NMR shifts.
AB  - An empirical equation, describing the relationship between the porphyrin methyl
      hyperfine shifts and the position of the axial ligand(s), has been applied to an
      artificial heme-protein in order to obtain insight into the active site
      properties of heme-protein models. 

PMID- 24584303
TI  - Acute adult onset comitant esotropia associated with accommodative spasm.
AB  - PURPOSE: Acute onset comitant esotropia associated with spasm of accommodation in
      children and adults is a rare clinical condition. When occurring with pupillary
      miosis and restricted ocular motility, it is referred to as "spasm of near
      reflex" (SNR) and may require neurological investigation. The natural history of
      SNR depends on its etiology. There is little information in the literature
      regarding the long-term follow-up of SNR and the stability of visual signs and
      symptoms following cessation of treatment. We report a case of SNR in an
      otherwise healthy young male, and discuss the presentation, clinical
      investigations, management, response to treatment, and 1-year follow-up. CASE
      REPORT: A 23-year-old male patient reported to the clinic with sudden onset of
      blurred vision, inward deviation of the eyes, and binocular diplopia. On
      examination, he was diagnosed to have acute onset esotropia resulting from SNR.
      He was treated with cycloplegic medications and vision therapy. The condition
      resolved following 1 year and there has been no recurrence. CONCLUSIONS: Acute
      adult onset esotropia occurring with accommodative spasm responds favorably to
      cycloplegic medications but may need a longer course of treatment for successful
      resolution and stability.

PMID- 24584304
TI  - Retinal tear presenting in a patient with ectrodactyly ectodermal dysplasia.
AB  - PURPOSE: This article aims to report a case of known ectrodactyly ectodermal
      dysplasia in a young male patient who subsequently was found to have a retinal
      tear and localized retinal detachment. CASE REPORT: This is a case report of a 22
      year-old white male patient with a history of ectrodactyly ectodermal dysplasia.
      Our patient initially presented with an acute exacerbation of bilateral, red,
      irritated eyes. No recent changes in vision were reported. The patient's ocular
      surface disease was consistent with ectrodermal dysplasia syndrome. However, a
      dilated fundus examination revealed an asymptomatic retinal tear with a
      surrounding localized retinal detachment. CONCLUSIONS: In this case, the patient
      presented with longstanding ocular surface disease known to be associated with
      this patient's inherited ectoderm disorder. In addition, this patient revealed a
      retinal tear, raising the possibility that patients with inherited congenital
      ectodermal dysplasia could be at risk for damaged structures originating from the
      neural ectoderm. In this heterogeneous disease, we are contributing to the
      existing literature a case of ectodermal dysplasia syndrome with obvious
      ectodermal complications that also had retinal findings leading us to speculate
      question if neural ectoderm could also be involved in this inherited disease.

PMID- 24584305
TI  - The expanding clinical spectrum of torpedo maculopathy.
AB  - PURPOSE: Torpedo maculopathy is an idiopathic, congenital, oval-shaped region of
      chorioretinal hypopigmentation located temporal to the macula. Torpedo lesions
      are typically unilateral, occasionally harbor an intraretinal cleft, and may be
      associated with varying degrees of hyperpigmentation. Visual acuity is usually
      normal, but the lesion may produce a scotoma in the visual field. There are no
      known associated systemic or ocular abnormalities. Diagnosis is based upon
      recognition of its characteristic shape and location. Because of its
      nonprogressive and generally benign nature, no treatment is required. CASE
      REPORTS: Two cases of torpedo maculopathy associated with fundus excavation are
      presented. To the best of our knowledge, this is the first reported association
      of torpedo maculopathy with fundus excavation. In one case, the visual acuity
      remained unaffected and in the other case the visual acuity was reduced to 20/50.
      In both cases, optical coherence tomography clearly demonstrates the excavated
      nature of the torpedo lesions. In case 1, where the visual acuity was normal, the
      excavation is remote from the fovea but in case 2, where the visual acuity was
      20/50, the excavation encroaches upon the fovea. In both cases, a scotoma
      corresponding to the excavated region could be demonstrated. CONCLUSIONS: Torpedo
      maculopathy is a usually benign condition associated with normal visual acuity
      and normal visual fields. Our cases demonstrate that torpedo maculopathy may be
      associated with excavation of the fundus and a corresponding scotoma in the
      visual field. Visual acuity may be compromised should the excavation encroach
      upon the central fovea. Knowledge of this previously unreported clinical
      manifestation of torpedo maculopathy may aid in advancing the understanding of
      this condition and the care of patients with the disorder.

PMID- 24584306
TI  - Branch retinal vein occlusion in an asymptomatic adult with cystic fibrosis.
AB  - PURPOSE: This article aims to describe a case of asymptomatic branch retinal vein
      occlusion (BRVO) in a patient with cystic fibrosis (CF) and discuss the possible
      link between the two. CASE REPORT: A young adult (aged 35 years) with CF who
      presented for routine ocular examination was found to have a superior temporal
      BRVO in the left eye. Visual acuity was unaffected, measuring -0.06 LogMAR, and
      intraocular pressure was 10 mm Hg. Optical coherence tomography showed no macular
      involvement. Regarding the patient's general health, blood pressure was within
      the normal range, and there was no diabetes. Exploratory blood tests revealed
      elevated fibrinogen levels. CONCLUSIONS: It is hypothesized that BRVO occurred
      secondary to raised fibrinogen levels, a common feature in CF resulting from
      chronic pulmonary infection and inflammation. Practitioners should be aware of
      the possible link between BRVO and CF.

PMID- 24584307
TI  - Two-step technique for posterior optic buttonholing of intraocular lens.
AB  - PURPOSE: This study aims to describe a two-step surgical technique for placement
      of a posterior chamber intraocular lens (IOL) in cases with crystalline lens
      subluxation resulting from non-progressive zonular dialysis. METHODS: The first
      stage entails a phacoemulsification with creation of a 4-mm posterior capsular
      opening using an automated vitrector. The second stage performed 6 weeks later
      includes an anterior vitrectomy and injection of a foldable three-piece IOL in
      the sulcus. The haptics of IOL are positioned in the sulcus while the optic is
      pushed behind the posterior capsular opening therefore "buttonholing" the IOL.
      RESULTS: Seven eyes of seven patients with posttraumatic zonular dialysis were
      operated using this technique. Follow-up of all cases revealed a well-centered
      IOL with good postoperative visual acuity (20/20 to 20/80). CONCLUSIONS: Our two
      stage surgical technique precludes the insertion of capsular tension ring in
      cases with non-progressive zonular dialysis. The technique is recommended in the
      presence of less than or equal to 6 clock hours of zonular dialysis with
      preexisting posterior capsular tear or herniation of vitreous in the anterior
      chamber.

PMID- 24584308
TI  - Tapioca melanoma of the iris without iris heterochromia.
AB  - PURPOSE: A case of a teenage girl with tapioca melanoma of the iris is presented.
      This case is unusual, as the patient did not have heterochromia and did not
      present with elevated intraocular pressure. CASE REPORT: A 14-year-old female
      patient presented with an amelanotic, multinodular, multifocal lesion of the
      right iris. Pathology confirmed a diagnosis of tapioca melanoma using
      immunohistologic staining. The patient underwent enucleation of her right eye and
      has been free of metastatic disease 3 years later. CONCLUSIONS: Tapioca melanoma
      of the iris must be included among the other differential diagnoses when
      examining patients with amelanotic iris lesions, even when iris heterochromia is
      not clearly evident.

PMID- 24584309
TI  - Changes are underway: my last editorial for you, with a roadmap and a call to
      action!

PMID- 24584310
TI  - Clipboard.

PMID- 24584311
TI  - Integrating a pharmacist into a home healthcare agency care model: impact on
      hospitalizations and emergency visits.
AB  - Medication regimens can be complicated during the transition from hospital to
      home for a variety of reasons. The primary purpose of this retrospective study
      was to measure the impact of integrating a pharmacist into a model of care at a
      Medicare-certified home healthcare agency for clients recently discharged from
      the hospital. The secondary purpose was to describe the medication-related
      problems among clients receiving services from the model of care involving a
      pharmacist. Integrating a pharmacist within the model of care demonstrated a
      positive clinical impact on clients. 

PMID- 24584312
TI  - Facilitators of diabetes self-management among rural individuals.
AB  - The prevalence of Type 2 diabetes mellitus has increased dramatically with a
      higher rate in rural populations. Diabetes self-management behaviors such as
      medication administration, blood glucose testing, and appropriate diet and
      exercise regimens must be implemented daily to increase chances of achieving
      therapeutic patient outcomes. Home healthcare clinicians are pivotal in assisting
      these individuals to be more self-confident and independent in managing their
      diabetes, achieving therapeutic goals, and addressing diabetes-related
      complications. This article will discuss facilitators of diabetes self-management
      in rural populations and implications for home healthcare clinicians. 

PMID- 24584313
TI  - Creating a meaningful infection control program: one home healthcare agency's
      lessons.
AB  - Creating a meaningful infection control program in the home care setting proved
      to be challenging for agency leaders of one hospital-based home healthcare
      agency. Challenges arose when agency leaders provided infection control (IC) data
      to the hospital's IC Committee. The IC Section Chief asked for national benchmark
      comparisons to align home healthcare reporting to that of the hospital level. At
      that point, it was evident that the home healthcare IC program lacked definition
      and structure. The purpose of this article is to share how one agency built a
      meaningful IC program. 

PMID- 24584314
TI  - Should my patient use a mechanical lift? Part 2: algorithm and case application.
AB  - The use of algorithms for safe patient handling in the acute care setting has
      been established and integrated into the standards of practice. This is not the
      case in the home care setting where the patient and caregivers are at risk for
      injury during patient transfers. Many factors need to be assessed before
      recommending a mechanical lift for home use. Some of the factors include the
      patient's weight-bearing status, cognitive level, and upper extremity strength,
      and the caregiver's ability to lift more than 35 pounds. All of these factors
      have been included in the clinical decision-making algorithm described in this
      article. Two case scenarios are presented to assist the reader with the analysis
      and application of the algorithm. 

PMID- 24584318
TI  - Information technology and home healthcare: the new frontier in home care.

PMID- 24584316
TI  - Palliative care hits a triple win: access, quality, and cost.
AB  - Like the generation before them, an ever-increasing proportion of baby boomers in
      the United States have a chronic illness and often multiple chronic illnesses,
      using ever-increasing national healthcare resources. With the Triple Aim, Don
      Berwick's overarching goals to help guide positive transformation to the
      healthcare system, palliative care can be seen as a valuable ally in the growing
      arsenal of models of care aimed at addressing the nation's needs. The SPARK
      Program, the palliative care management program of a large home care agency in a
      metropolitan area, was created to address the needs of patients with chronic
      serious illness and palliative care needs. 

PMID- 24584319
TI  - The cost of observation.

PMID- 24584320
TI  - Has science started to go wrong?

PMID- 24584321
TI  - Value of high resolution compression elastography and color doppler sonography in
      characterisation of breast lesions: comparison of different high-frequency
      transducers.
AB  - PURPOSE: To evaluate the additional effect of higher frequent linear probes than
      12.5 MHz in color Doppler sonography and free hand sonoelastography of benign and
      malignant breast masses and to compare different color encodings in
      sonoelastography. MATERIALS AND METHODS: From December 2012 to March 2013, 37
      patients with benign or malignant breast masses were prospectively included in
      this study. All solid masses have been histologically proven. Two readers
      assessed sonoelastographic findings at 12.5 MHz vs. 17 MHz according to the
      tsukuba elasticity score and additionally different color encodings were
      compared. Results of Doppler sonography using a score of 0, 1 or 2, depending on
      the degree of perfusion, also were assessed at 12.5 MHz vs. 17 MHz. RESULTS:
      Among the 37 examined breast masses there were 10 cysts, 16 fibroadenomas and 11
      carcinomas. Median participant age was 49.0 years. Use of color Doppler
      sonography enabled to distinguish cysts from solid breast masses (p < 0.001),
      without an improvement at 17 MHz. Additional sonoelastography significantly
      improved the specificity in solid breast masses (p < 0.001). No changes could be
      seen using different colors in sonoelastography. CONCLUSION: Combination of color
      Doppler sonography and sonoelastography can increase the accuracy in
      distinguishing benign from malignant breast masses. The use of linear probes with
      a higher frequency than 12.5 MHz does not show any benefit, neither in color
      Doppler sonography nor in sonoelastography.

PMID- 24584322
TI  - Influence of non-Newtonian viscosity of blood on microvascular impairment.
AB  - The present research investigated the role of blood viscosity on flow within a
      microvascular network to identify the conditions of blood flow stagnation. When
      the yield stress of blood was less than 0.005 Pa, there were no stagnant regions
      in the microvasculature. However, when the yield stress increased to 0.05 Pa,
      stagnant or reduced flow areas began to appear, which grew and expanded rapidly
      with further increase in the yield stress. Thus, the yield stress determined from
      blood viscosity profile of a patient can be utilized to evaluate the risk of
      circulatory impairment. 

PMID- 24584323
TI  - Adherence and shear-resistance of primary human endothelial cells on smooth
      poly(ether imide) films.
AB  - BACKGROUND: Occlusions of artificial small-diameter cardiovascular grafts are
      frequent events after implantation, often caused by clot formations. A main
      factor is the insufficient hemocompatibility of the inner artificial graft
      surface, which could be improved by endothelialization. Therefore, one challenge
      in cardiovascular graft engineering is the establishment of a shear-resistant
      endothelial cell layer to prevent cell detachment by shear forces after
      implantation. MATERIALS AND METHODS: Recently, very smooth (Rq = 2.37 +/- 1.40
      nm) poly(ether imide) (PEI) films were introduced as a biocompatible candidate
      material for cardiovascular devices. In this study the stability of primary human
      umbilical vein endothelial cell (HUVEC) monolayer was investigated after long
      term seeding (nine days) on PEI-films and subsequent exposure to a venous shear
      stress of 3 dyn/cm2 for up to six hours using the cone-and-plate shearing
      technique. Cell density, growth pattern and morphology of HUVEC were determined
      prior and after shearing compared to glass as control substrate. HUVEC adhering
      to the substrate after shear stress were counted and analyzed by fluorescent
      staining. Supernatants were collected and secretion profile analysis of
      vasoactive and inflammatory mediators was performed. RESULTS: The cell density on
      PEI-films compared to the controls was slightly higher after long-term seeding
      and exposure to shear stress (glass: 71,656 +/- 8,830 cells/cm2 and 42,239 +/-
      5,607 cells/cm2; PEI-film: 64,056 +/- 2,829 cells/cm2 and 45,422 +/- 2,507
      cells/cm2 before and after shear stress, respectively). Actin- and vinculin
      staining revealed a scattered re-organization of the cytoskeleton as well as a
      formation of stress fibers and focal adhesion points. Secretion of prostacyclin
      and thromboxane A2 was increased after application of shear stress, but no
      significant differences were detectable between cells growing on PEI-films or
      glass. Amounts of secreted inflammatory cytokines IL-6 and IL-8 in the
      supernatant were significantly lower for HUVEC seeded on PEI-films compared to
      glass before as well as after stress. CONCLUSION: The study demonstrated that
      HUVEC were able to resist exposure to venous shear stress when seeded on smooth
      PEI-films with typical morphology and adhesion behavior. However, HUVEC adherence
      on PEI was not yet sufficient to retain a complete cell monolayer after shear
      stress exposure. Occasionally, single cells or cell plaques were disrupted
      resulting in cell free areas in the confluent HUVEC layer. Apart from this our
      data suggest that PEI is a suitable substrate for HUVEC under static and dynamic
      conditions and therefore a promising candidate material for cardiovascular
      applications. The next objective is a surface functionalization of the PEI-films
      in a cell specific manner to reach a functionally confluent, shear resistant
      HUVEC monolayer.

PMID- 24584324
TI  - Interaction of poly(ether imide) films with early immune mechanisms.
AB  - With the worldwide increase of atherosclerosis, the need for new engineered
      patient specific implants such as stents or vascular grafts is still emerging.
      Recently, very smooth poly(ether imide) (PEI) films were, based on their
      hemocompatibility and compatibility with endothelial cells, suggested as
      potential biomaterial for cardiovascular applications. In atherosclerosis, immune
      mechanisms such as complement activation, but also cellular responses such as
      monocytes and neutrophils activation, can mediate the inflammatory response.
      Therefore, it is important that the implant material itself does not trigger the
      inflammatory response. Early immune mechanisms - e.g. macrophage activation,
      complement induction, generation of reactive oxygen species (ROS), and the
      secretion of inflammatory cytokines by leukocytes - could potentiate the
      inflammatory responses, and may thereby alter endothelial cells behaviour or
      facilitate platelet activation. Therefore, it is important to evaluate the immuno
      compatibility of PEI-films. The PEI-films were fabricated from commercially
      available PEI, which was dissolved in dichloromethane and pulled out on a
      cleaned, smooth glass surface and subsequently, solvent residues were removed
      during the drying procedure. Using a murine macrophage reporter cell line
      possible material bound microbial contaminations and material intrinsic immuno
      stimulatory properties were investigated. The macrophages were viable after
      adhering on the PEI-films and did not show signs of activation, indicating that
      the used PEI-film was free of microbial contaminations. To determine whether PEI
      films induced complement activation, the release of C5a in pooled human plasma
      was analyzed. The detected C5a levels did not differ between PEI-films and tissue
      culture plates (TCP), which served as control material. Furthermore, in whole
      human blood, the generation of ROS as well as the cytokine production were
      investigated by flow cytometry and by multiplex bead arrays, respectively. The
      production of IL-6 and TNF-alpha as well as the generation of ROS by immune cells
      of the whole blood was not induced upon contact with PEI-films. The immunological
      evaluation of PEI-films revealed that no substantial activation of the
      investigated early immune mechanisms occurred. Altogether, this data demonstrate
      that PEI is immuno-compatible and from that perspective may be a suitable
      biomaterial for cardiovascular applications. 

PMID- 24584325
TI  - Numerical analysis of 3D blood flow and common carotid artery hemodynamics in the
      carotid artery bifurcation with stenosis.
AB  - The results for blood flow in the carotid artery bifurcation on the basis of
      numerical simulation of Navier-Stokes equations are presented in this study. Four
      cases of carotid bifurcation are considered: common carotid artery (CCA)
      bifurcation without stenoses and cases with one, two and three stenoses are also
      presented. The results are obtained by performing numerical simulations
      considering one pulse wave period based on the finite volume discretization of
      Navier-Stokes equations. The structures of the flow around the bifurcation are
      obtained and the deformation of the pulse wave from common carotid artery (CCA)
      to the internal carotid artery (ICA) and external carotid artery (ECA) is traced.
      The axial velocity and wall shear stress (WSS) distribution and contours are
      presented considering the characteristic time points. The results of the WSS
      distribution around the bifurcation allow a prediction of the probable sites of
      stenosis growth. 

PMID- 24584326
TI  - Synthesis and anion binding studies of o-phenylenevinylene-bridged tetrapyrrolic
      macrocycle as an expanded analogue of calix[4]pyrrole.
AB  - An o-phenylenevinylene-bridged tetrapyrrolic macrocycle (2) was synthesized by
      means of a Horner-Wadsworth-Emmons reaction between benzylbisphosphonate and SEM
      protected diformylpyrrole, followed by deprotection of the SEM groups. This
      conformationally flexible tetrapyrrole can be considered as an expanded
      calix[4]pyrrole analogue, which acts as a receptor for the chloride and bromide
      anions in THF-d8, but undergoes deprotonation upon exposure to the fluoride
      anion.

PMID- 24584327
TI  - Variability in content of homemade diets for canine chronic kidney disease.

PMID- 24584328
TI  - Cigarette exposure, dependence, and craving are related to insula thickness in
      young adult smokers.
AB  - The age period spanning late adolescence to emergent adulthood is associated with
      the highest prevalence of cigarette smoking in the United States, and is also a
      time of continued brain development. Nonetheless, although prior research has
      shown group differences in brain structure associated with smoking status in
      adults, few studies have examined how smoking and associated behavioral states
      relate to brain structure in this age group. Neuroimaging and lesion studies have
      suggested that the insula, a cortical region that integrates heterogeneous
      signals about internal states and contributes to executive functions, plays an
      important role in cigarette smoking behavior. Using high-resolution structural
      magnetic resonance imaging, we therefore measured cortical thickness of the
      insula in 18 smokers and 24 nonsmokers between the ages of 16 and 21 years. There
      were no group differences in insula thickness, but cigarette exposure (pack
      years) was negatively associated with thickness in right insula. Cigarette
      dependence and the urge to smoke were negatively related to cortical thickness in
      the right ventral anterior insula. Although the results do not demonstrate
      causation, they do suggest that there are effects of cigarette exposure on brain
      structure in young smokers, with a relatively short smoking history. It is
      possible that changes in the brain due to prolonged exposure or to the
      progression of dependence lead to more extensive structural changes, manifested
      in the reported group differences between adult smokers and nonsmokers.
      Structural integrity of the insula may have implications for predicting long-term
      cigarette smoking and problems with other substance abuse in this population. 

PMID- 24584329
TI  - Incubation of methamphetamine and palatable food craving after punishment-induced
      abstinence.
AB  - In a rat model of drug craving and relapse, cue-induced drug seeking
      progressively increases after withdrawal from methamphetamine and other drugs, a
      phenomenon termed 'incubation of drug craving'. However, current experimental
      procedures used to study incubation of drug craving do not incorporate negative
      consequences of drug use, which is a common factor promoting abstinence in
      humans. Here, we studied whether incubation of methamphetamine craving is
      observed after suppression of drug seeking by adverse consequences (punishment).
      We trained rats to self-administer methamphetamine or palatable food for 9 h per
      day for 14 days; reward delivery was paired with a tone-light cue. Subsequently,
      for one group within each reward type, 50% of the lever-presses were punished by
      mild footshock for 9-10 days, whereas for the other group lever-presses were not
      punished. Shock intensity was gradually increased over time. Next, we assessed
      cue-induced reward seeking in 1-h extinction sessions on withdrawal days 2 and
      21. Response-contingent punishment suppressed extended-access methamphetamine or
      food self-administration; surprisingly, food-trained rats showed greater
      resistance to punishment than methamphetamine-trained rats. During the relapse
      tests, both punished and unpunished methamphetamine- and food-trained rats showed
      significantly higher cue-induced reward seeking on withdrawal day 21 than on day
      2. These results demonstrate that incubation of both methamphetamine and food
      craving occur after punishment-induced suppression of methamphetamine or
      palatable food self-administration. Our procedure can be used to investigate
      mechanisms of relapse to drug and palatable food seeking under conditions that
      more closely approximate the human condition.

PMID- 24584331
TI  - The neuroeconomics of alcohol demand: an initial investigation of the neural
      correlates of alcohol cost-benefit decision making in heavy drinking men.
AB  - Neuroeconomics integrates concepts and methods from psychology, economics, and
      cognitive neuroscience to understand how the brain makes decisions. In economics,
      demand refers to the relationship between a commodity's consumption and its cost,
      and, in behavioral studies, high alcohol demand has been consistently associated
      with greater alcohol misuse. Relatively little is known about how the brain
      processes demand decision making, and the current study is an initial
      investigation of the neural correlates of alcohol demand among heavy drinkers.
      Using an event-related functional magnetic resonance imaging (fMRI) paradigm,
      participants (N=24) selected how much they would drink under varying levels of
      price. These choices determined access to alcohol during a subsequent bar
      laboratory self-administration period. During decisions to drink in general,
      greater activity was present in multiple distinct subunits of the prefrontal and
      parietal cortices. In contrast, during decisions to drink that were demonstrably
      affected by the cost of alcohol, significantly greater activation was evident in
      frontostriatal regions, suggesting an active interplay between cognitive
      deliberation and subjective reward value. These choices were also characterized
      by significant deactivation in default mode network regions, suggesting
      suppression resulting from greater cognitive load. Across choice types, the
      anterior insula was notably recruited in diverse roles, further implicating the
      importance of interoceptive processing in decision-making behavior. These
      findings reveal the neural signatures subserving alcohol cost-benefit decision
      making, providing a foundation for future clinical applications of this paradigm
      and extending this approach to understanding the neural correlates of demand for
      other addictive commodities. 

PMID- 24584335
TI  - Documented quality of care in certified colorectal cancer centers in Germany:
      German Cancer Society benchmarking report for 2013.
AB  - PURPOSE: In order to improve the quality of treatment for cancer patients the
      German Cancer Society (Deutsche Krebsgesellschaft) implemented a certification
      system for oncological care institutions. The certified colorectal cancer centers
      present the structures, processes and results of their network in the framework
      of an auditing procedure. METHODS: The current benchmarking report by the
      certified centers reflects the centers' reference results over a period of 3
      years. The figures included in the benchmarking report reflect the areas of
      interdisciplinary collaboration, guideline-compliant treatment, and expertise of
      the main treatment partners. RESULTS: High percentages were shown for indicators
      reflecting pretreatment and postoperative case presentations in multidisciplinary
      team meetings (91.8 % or 98.1 %), psycho-oncologic care (54.8 %) as well as
      social service counseling (77.1 %). Good quality of the TME rectal specimen and
      adequate lymph-node retrieval (12 lymph nodes at least) was achieved by 93 % or
      96.6 % of the centers. Adjuvant chemotherapy (colon, Union for International
      Cancer Control [UICC] stage III) or neoadjuvant radiotherapy or chemoradiotherapy
      (rectum, UICC stages II and III) received 73.7 % or 80 % of relevant patients.
      Quotas of anastomotic leakage in the colon or rectum were 4.4 % or 7.6 %, whereas
      postoperative mortality amounted to 2.6 %. CONCLUSIONS: The present analysis of
      the results, together with the centers' statements and the auditors' reports,
      shows that most of the targets for indicator figures are being better met over
      the course of time. In addition, however, there is a clear potential for
      improvement and the centers are verifiably addressing this. A transparent
      presentation of the quality of care and reflection on and discussion of the
      results among the treatment partners in the certified network and with the
      auditors during the certification process may contribute to constant quality
      improvement in oncological care.

PMID- 24584330
TI  - Dopamine D3 receptor is necessary for ethanol consumption: an approach with
      buspirone.
AB  - Mesolimbic dopamine (DA) controls drug- and alcohol-seeking behavior, but the
      role of specific DA receptor subtypes is unclear. We tested the hypothesis that
      D3R gene deletion or the D3R pharmacological blockade inhibits ethanol preference
      in mice. D3R-deficient mice (D3R(-/-)) and their wild-type (WT) littermates,
      treated or not with the D3R antagonists SB277011A and U99194A, were tested in a
      long-term free choice ethanol-drinking (two-bottle choice) and in a binge-like
      ethanol-drinking paradigm (drinking in the dark, DID). The selectivity of the D3R
      antagonists was further assessed by molecular modeling. Ethanol intake was
      negligible in D3R(-/-) and robust in WT both in the two-bottle choice and DID
      paradigms. Treatment with D3R antagonists inhibited ethanol intake in WT but was
      ineffective in D3R(-/-) mice. Ethanol intake increased the expression of RACK1
      and brain-derived neurotrophic factor (BDNF) in both WT and D3R(-/-); in WT there
      was also a robust overexpression of D3R. Thus, increased expression of D3R
      associated with activation of RACK1/BDNF seems to operate as a reinforcing
      mechanism in voluntary ethanol intake. Indeed, blockade of the BDNF pathway by
      the TrkB selective antagonist ANA-12 reversed chronic stable ethanol intake and
      strongly decreased the striatal expression of D3R. Finally, we evaluated
      buspirone, an approved drug for anxiety disorders endowed with D3R antagonist
      activity (confirmed by molecular modeling analysis), that resulted effective in
      inhibiting ethanol intake. Thus, DA signaling via D3R is essential for ethanol
      related reward and consumption and may represent a novel therapeutic target for
      weaning. 

PMID- 24584333
TI  - Petrous apex lesions in the pediatric population.
AB  - A variety of abnormal imaging findings of the petrous apex are encountered in
      children. Many petrous apex lesions are identified incidentally while images of
      the brain or head and neck are being obtained for indications unrelated to the
      temporal bone. Differential considerations of petrous apex lesions in children
      include "leave me alone" lesions, infectious or inflammatory lesions, fibro
      osseous lesions, neoplasms and neoplasm-like lesions, as well as a few rare
      miscellaneous conditions. Some lesions are similar to those encountered in
      adults, and some are unique to children. Langerhans cell histiocytosis (LCH) and
      primary and metastatic pediatric malignancies such as neuroblastoma,
      rhabomyosarcoma and Ewing sarcoma are more likely to be encountered in children.
      Lesions such as petrous apex cholesterol granuloma, cholesteatoma and
      chondrosarcoma are more common in adults and are rarely a diagnostic
      consideration in children. We present a comprehensive pictorial review of CT and
      MRI appearances of pediatric petrous apex lesions. 

PMID- 24584347
TI  - MicroRNA-23a mediates post-transcriptional regulation of CXCL12 in bone marrow
      stromal cells.
AB  - The chemokine CXCL12 regulates the interaction between hematopoietic stem and
      progenitor cells and bone marrow stromal cells. Although its relevance in the
      bone marrow niche is well recognized, the regulation of CXCL12 by microRNA is not
      completely understood. We transfected a library of 486 microRNA in the bone
      marrow stromal cell line SCP-1 and studied the expression of CXCL12. Twenty-seven
      microRNA were shown to downregulate expression of CXCL12. Eight microRNA (miR
      23a, 130b, 135, 200b, 200c, 216, 222, and 602) interacted directly with the 3'UTR
      of CXCL12. Next, we determined that only miR-23a is predicted to bind to the
      3'UTR and is strongly expressed in primary bone marrow stromal cells. Modulation
      of miR-23a changes the migratory potential of hematopoietic progenitor cells in
      co-culture experiments. We discovered that TGFB1 mediates its inhibitory effect
      on CXCL12 levels by upregulation of miR-23a. This process was partly reversed by
      miR-23a molecules. Finally, we determined an inverse expression of CXCL12 and miR
      23a in stromal cells from patients with myelodys-plastic syndrome indicating that
      the interaction has a pathophysiological role. Here, we show for the first time
      that CXCL12-targeting miR23a regulates the functional properties of the
      hematopoietic niche. 

PMID- 24584348
TI  - Molecular analysis of Fanconi anemia: the experience of the Bone Marrow Failure
      Study Group of the Italian Association of Pediatric Onco-Hematology.
AB  - Fanconi anemia is an inherited disease characterized by congenital malformations,
      pancytopenia, cancer predisposition, and sensitivity to cross-linking agents. The
      molecular diagnosis of Fanconi anemia is relatively complex for several aspects
      including genetic heterogeneity with mutations in at least 16 different genes. In
      this paper, we report the mutations identified in 100 unrelated probands enrolled
      into the National Network of the Italian Association of Pediatric Hematoly and
      Oncology. In approximately half of these cases, mutational screening was carried
      out after retroviral complementation analyses or protein analysis. In the other
      half, the analysis was performed on the most frequently mutated genes or using a
      next generation sequencing approach. We identified 108 distinct variants of the
      FANCA, FANCG, FANCC, FANCD2, and FANCB genes in 85, 9, 3, 2, and 1 families,
      respectively. Despite the relatively high number of private mutations, 45 of
      which are novel Fanconi anemia alleles, 26% of the FANCA alleles are due to 5
      distinct mutations. Most of the mutations are large genomic deletions and
      nonsense or frameshift mutations, although we identified a series of missense
      mutations, whose pathogenetic role was not always certain. The molecular
      diagnosis of Fanconi anemia is still a tiered procedure that requires identifying
      candidate genes to avoid useless sequencing. Introduction of next generation
      sequencing strategies will greatly improve the diagnostic process, allowing a
      rapid analysis of all the genes. 

PMID- 24584349
TI  - Interactions between comorbidity and treatment of chronic lymphocytic leukemia:
      results of German Chronic Lymphocytic Leukemia Study Group trials.
AB  - This study investigated the impact of comorbidity in 555 patients with chronic
      lymphocytic leukemia enrolled in two trials of the German Chronic Lymphocytic
      Leukemia Study Group on first-line treatment with fludarabine plus
      cyclophosphamide, fludarabine, or chlorambucil. Patients with two or more
      comorbidities and patients with less than two comorbidities differed in overall
      survival (71.7 versus 90.2 months; P<0.001) and progression-free survival (21.0
      versus 31.5 months; P<0.01). After adjustment for other prognostic factors and
      treatment, comorbidity maintained its independent prognostic value in a
      multivariate Cox regression analysis. Chronic lymphocytic leukemia was the major
      cause of death in patients with two or more comorbidities. Disease control in
      patients with two or more comorbidities was better with fludarabine plus
      cyclophosphamide than with fludarabine treatment, but not with fludarabine
      compared to chlorambucil treatment. These results give insight into interactions
      between comorbidity and therapy of chronic lymphocytic leukemia and suggest that
      durable control of the hematologic disease is most critical to improve overall
      outcome of patients with increased comorbidity. The registration numbers of the
      trials reported are NCT00276848 and NCT00262795. 

PMID- 24584350
TI  - The importance of harmonizing interim positron emission tomography in non-Hodgkin
      lymphoma: focus on the Deauville criteria.

PMID- 24584351
TI  - DDX3X-MLLT10 fusion in adults with NOTCH1 positive T-cell acute lymphoblastic
      leukemia.

PMID- 24584353
TI  - Amyloid precursor protein regulates neurogenesis by antagonizing miR-574-5p in
      the developing cerebral cortex.
AB  - Amyloid precursor protein (APP) is a transmembrane glycoprotein proteolytically
      processed to release amyloid beta, a pathological hallmark of Alzheimer's
      disease. APP is expressed throughout the developing and mature brain; however,
      the primary function of this protein is unknown. We previously demonstrated that
      APP deficiency enhances neurogenesis, but the mechanisms underlying this process
      are not known. Here we show that APP regulates the expression of microRNAs in the
      cortex and in neural progenitors, specifically repressing miR-574-5p. We also
      show that overexpression of miR-574-5p promotes neurogenesis, but reduces the
      neural progenitor pool. In contrast, the reduced expression of miR-574-5p
      inhibits neurogenesis and stimulates proliferation in vitro and in utero. We
      further demonstrate that the inhibition of miR-574-5p in APP-knockout mice
      rescues the phenotypes associated with APP deficiency in neurogenesis. Taken
      together, these results reveal a mechanism in which APP regulates the
      neurogenesis through miRNA-mediated post-transcriptional regulation. 

PMID- 24584360
TI  - YAP overexpression affects tooth morphogenesis and enamel knot patterning.
AB  - Teeth develop through distinct morphological stages. At the cap stage, a
      compactly clustered and concentrically arranged cell mass, the enamel knot,
      appears at the tip of the enamel organ. Cells in this knot express sets of key
      molecules, and as such have been proposed to act as a signaling center directing
      tooth morphogenesis and tooth cusp formation. YAP is a transcriptional co
      activator of the Hippo signaling pathway that is essential for the proper
      regulation of organ growth. In this study, we analyzed the tooth phenotype in
      transgenic mice that overexpressed a constitutively active form of YAP in the
      dental epithelium. We found that overexpression of YAP resulted in deformed tooth
      morphogenesis with widened dental lamina. In addition, the enamel knot was
      mislocated to the upper portion of the enamel organ, where it remained devoid of
      proliferating cells and contained apoptotic cells with intense Edar transcripts
      and reduced E-cadherin expression. Interestingly, some signaling molecules, such
      as Shh, Fgf4, and Wnt10a, were not expressed in this mislocated enamel knot, but
      remained at the tip of the enamel organ. Analysis of these data suggests that the
      signaling center is induced by reciprocal epithelial-mesenchymal interactions,
      and its induction may be independent of the enamel knot. 

PMID- 24584361
TI  - Screening and characterization of Sphingomonas sp. mutant for welan gum
      biosynthesis at an elevated temperature.
AB  - The optimal temperature for the microbial polysaccharide fermentation is no
      higher than 30  degrees C, which is economically undesirable due to additional
      cooling cost. To solve this problem in the case of welan gum production, we
      obtained the high-temperature-tolerant-producing strain, Sphingomonas sp. HT-1 by
      atmospheric and room-temperature plasma-induced mutation. Using HT-1, we obtained
      a concentration and 1 % aqueous viscosity of 26.8 +/- 0.34 g/L and 3.50 +/- 0.05
      Pa s at a comparatively higher optimal temperature (37  degrees C). HT-1 was
      further characterized to understand the mechanism by which these properties are
      improved. Results indicated that high yield could be attributed to the following:
      (1) enhanced intracellular synthesis, demonstrated by an increase in the
      activities of key enzymes, and (2) accelerated cross-membrane substrate uptake
      and product secretion, indicated by improved membrane fluidity and permeability.
      Temperature tolerance could be attributed to the overexpression of the
      investigated heat shock proteins and oxidative stress proteins. 

PMID- 24584352
TI  - ATM mutation rather than BIRC3 deletion and/or mutation predicts reduced survival
      in 11q-deleted chronic lymphocytic leukemia: data from the UK LRF CLL4 trial.
AB  - ATM mutation and BIRC3 deletion and/or mutation have independently been shown to
      have prognostic significance in chronic lymphocytic leukemia. However, the
      relative clinical importance of these abnormalities in patients with a deletion
      of 11q encompassing the ATM gene has not been established. We screened a cohort
      of 166 patients enriched for 11q-deletions for ATM mutations and BIRC3 deletion
      and mutation and determined the overall and progression-free survival among the
      133 of these cases treated within the UK LRF CLL4 trial. SNP6.0 profiling
      demonstrated that BIRC3 deletion occurred in 83% of 11q-deleted cases and always
      co-existed with ATM deletion. For the first time we have demonstrated that 40% of
      BIRC3-deleted cases have concomitant deletion and mutation of ATM. While BIRC3
      mutations were rare, they exclusively occurred with BIRC3 deletion and a wild
      type residual ATM allele. In 11q-deleted cases, we confirmed that ATM mutation
      was associated with a reduced overall and progression-free survival comparable to
      that seen with TP53 abnormalities, whereas BIRC3 deletion and/or mutation had no
      impact on overall and progression-free survival. In conclusion, in 11q-deleted
      patients treated with first-line chemotherapy, ATM mutation rather than BIRC3
      deletion and/or mutation identifies a subgroup with a poorer outcome. 

PMID- 24584362
TI  - Self-assembled nanowire array capacitors: capacitance and interface state
      profile.
AB  - Direct characterization of the capacitance and interface states is very important
      for understanding the electronic properties of a nanowire transistor. However,
      the capacitance of a single nanowire is too small to precisely measure. In this
      work we have fabricated metal-oxide-semiconductor capacitors based on a large
      array of self-assembled Si nanowires. The capacitance and conductance of the
      nanowire array capacitors are directly measured and the interface state profile
      is determined by using the conductance method. We demonstrate that the nanowire
      array capacitor is an effective platform for studying the electronic properties
      of nanoscale interfaces. This approach provides a useful and efficient metrology
      for the study of the physics and device properties of nanoscale metal-oxide
      semiconductor structures. 

PMID- 24584363
TI  - Ultra-small droplet generation via volatile component evaporation.
AB  - In this paper, we present a novel method to generate ultra-small droplets via
      volatile component evaporation. By regulating the composition of the binary
      solvent, the volume ratio of the high saturated vapor pressure component, and the
      flow rate ratio of the two phases, monodisperse ultra-small water or nonvolatile
      organic droplets can be formed. This method is flexible, versatile, and
      compatible with tip-streaming or nanofluidics, and may have potential
      applications in single molecule assay, colloid synthesis, and block copolymer
      assembly. 

PMID- 24584364
TI  - Evaluation of TH agglutinin titres of Widal test in the diagnosis of typhoid
      fever.
AB  - This prospective study was evaluated the role of TH agglutinins and reevaluate
      the diagnostic value of Widal test in the diagnosis of typhoid fever by
      identifying the S. typhi specific antibody. The study was carried out in the
      department of Microbiology, Mymensingh Medical College, Mymensingh between July
      2010 and June 2011, including 200 individuals of different ages and sexes. Widal
      test and blood culture were performed for each of the cases and controls. Among
      150 blood samples from the suspected cases, 23(15.3%) were culture positive for
      S. typhi and 67(44.7%) had high titres of >=1:160 for 'O' or 'H' or both
      agglutinins. Out of 23 culture positive cases, 3(13%) had TO >=:160, 5(21.7%) had
      significant TH >=1:160. Based on the above findings, it was concluded that
      judicious interpretation of Widal test play an essential role in diagnosis of
      typhoid fever, especially in the resource poor countries like Bangladesh.

PMID- 24584365
TI  - Correlation between grades of intraventricular hemorrhage and severity of hypoxic
      ischemic encephalopathy in perinatal asphyxia.
AB  - This study was done to find out the correlation between various grades of
      Intraventricular Hemorrhage (IVH) and stages of HIE in perinatal asphyxia and to
      determine the short-term outcome of the affected baby. This observational study
      was conducted in Neonatal ward of Dhaka Shishu Hospital (DHS) and Dhaka Medical
      College Hospital for period of 37 months from January 2004 to January 2007. Total
      189 perinatally asphyxiated babies were enrolled for HIE staging and cranial
      Ultrasonogram (USG) to find out grades of IVH. Finally 178 newborns were
      fulfilling all the necessary criteria for statistical analysis of the collected
      data on prescribed questionnaire. Among 178 perinatally asphyxiated newborns HIE
      stages - I, II, III were 50(28%), 10(56%) and 28(16%) respectively. Out of this
      178 neonates total 50(28%) developed various grades IVH. Grades of IVH, I, II,
      III, IV were 15(30%), 18(36%), 10(20%) and 7(14%) respectively. There was
      significant correlation between the severity of HIE staging and grades of IVH.
      Short term outcome was poor in HIE-III, IVH grade III and IV. There is a direct
      relationship between different grades of IVH and stages of HIE. That is more the
      severe stages of HIE there is more chances to develop severe grades of IVH,
      Immediate morbidity and mortality is dependent on the grades of IVH and severity
      of stages of HIE. 

PMID- 24584366
TI  - Sling for correcting uterine prolapse: twelve years experience.
AB  - Pelvic organ prolapse is a common morbidity among Bangladeshi women. Both patient
      and surgeon prefer vaginal hysterectomy for the treatment of this condition and
      occasionally they choose Fothergill's operation. Uterine suspension is suitable
      for the young women to preserve the uterus. This observational study was carried
      out in three teaching hospitals and two other non government hospitals for the
      period of 12 years among 280 patients with 1st, 2nd and 3rd degree uterine
      prolapse. Follow up done at 6th week , 6th month, 1st year, 5th year, 10th year
      and 12th year for recurrence of prolapse, dragging pain and dyspareunia. Among
      280 patients >60% patients were of 26-30 years age group. In last follow up at
      12th year 2(0.71%) women complained feeling of some descend of uterus, 1(0.36%)
      complained dragging pain in abdomen and I (0.36%) complained dyspareunia. All
      patients expressed satisfaction which indicates psychological well being. Uterine
      sling is an effective procedure to save uterus in young women to improve their
      quality of life. 

PMID- 24584367
TI  - Effect of levodopa and carbidopa on non-motor symptoms and signs of Parkinson's
      disease.
AB  - Parkinson's disease (PD) patient presents with both motor and non-motor symptoms.
      This was descriptive type of interventional study carried out in the department
      of Neurology, Mymensingh Medical College Hospital, Mymensingh, Bangladesh from
      January 2009 to December 2010. Among the total 59 cases, 51 completed the
      proposed five months follow up. The rest eight cases attended Neurology
      department irregularly and were ultimately dropout from follow up. The case
      selection technique was purposive type of non probability sampling. Each patient
      was treated with levodopa+carbidopa. Then the effect of levodopa+carbidopa on non
      motor symptoms and signs were evaluated in subsequent five visits at four week
      interval. All relevant information and follow-up were recorded in a pre-designed
      individual case record form. Chi square test was done and probability value <0.05
      were considered as level of significance with 95% confidence limit. Among the non
      motor symptoms (NMS), the most frequent symptoms at base line visit were fatigue
      56.8%, excessive sweating 54.9%, insomnia 54.9%, akathisia 47.1%, anxiety 45.1%,
      constipation 17.6%. After five months of levodopa+carbidopa therapy, frequencies
      of most of the NMS decreased slightly in comparison to base line symptoms but
      there were no significant effect of levodopa+carbidopa on NMS of study subjects. 

PMID- 24584368
TI  - Role of adenosine deaminase in diagnosis of tubercular pleural effusion.
AB  - The diagnosis of pleural tuberculosis (TB) continues to be a challenge in
      clinical practice. Traditional diagnostic methods are very useful for the
      diagnosis of pulmonary TB but have a low yield when applied to pleural fluid. It
      is produced during the inflammatory process triggered by the M. tuberculosis.
      Usefulness of adenosine deaminase (ADA) estimation in pleural fluid has been
      shown as a reliable chemical bio-marker specially when there is suspicion of
      tuberculosis in endemic areas. ADA level was determined in the pleural fluid of
      100 patients present with pleural effusion admitted at Mymensingh Medical College
      Hospital during the period of March 2012 to September 2012. ADA level was >40IU/L
      among the 52 tubercular pleural effusion patients with sensitivity & specificity
      is 100% and 66% respectively. Thus is evident that ADA level can be used along
      with conventional methods for diagnosis of pleural TB.

PMID- 24584369
TI  - Serum magnesium in hospital admitted diabetic patients.
AB  - Magnesium depletion has a negative impact on glucose homeostasis and insulin
      sensitivity in diabetic patients. Low plasma magnesium concentration is a highly
      specific indicator of poor magnesium status. This case control study was
      conducted in Mymensingh Medical College Hospital, Bangladesh, from May 2011 to
      April 2012. This study was done to assess the serum magnesium level in diabetic
      and non-diabetic patients and to find out the association between serum
      magnesium, blood glucose and duration of diabetes mellitus. Serum magnesium
      concentrations were determined in 50 diabetics and 50 age and sex matched non
      diabetic patients or attendants for controls. Among the case and control group 32
      were male and 18 were female. Mean age of control group was 54.42+/-2.33 and
      study group was 55.78+/-2.43 years. Duration of diabetes of case group in which
      50% of patients have diabetes for up to 4 years, 18% of patients have diabetes
      for 5-9 years, 5% of patients have for 10-14 years and 2% of patients have
      diabetes for 15 years and above. Serum magnesium concentrations below the normal
      reference range for study group was 44% and control group was 6%. The mean serum
      magnesium level of study group was 0.70+/-0.01mmol/L and that of control group
      was 0.83+/-0.02mmol/L. So, the difference in serum magnesium level between two
      groups were statistically highly significant (p = 0.001). Correlation between FBS
      and SML of study group, which is negative (r = - 0.182). There is opposite
      relation among the characteristics as r is negative. And also correlation between
      2HAFB and SML of study group, which is negative (r = - 0.06). There is opposite
      relation among the characteristics as r is negative. 

PMID- 24584370
TI  - Color Doppler sonography and resistivity index in the differential diagnosis of
      hepatic neoplasm.
AB  - The purpose of this study was to determine the usefulness of color doppler
      sonography and resistivity index (RI) in differentiating liver tumors. The study
      was carried out in the Department of Radiology and Imaging, Mymensingh Medical
      College Hospital, and Institute of Nuclear Medicine and Allied Sciences (INMAS),
      Mymensingh, Bangladesh, during the period of July 2009 to June 2011. Total 50
      consecutive cases were studied. Among them 27 were hepatocellular carcinomas, 19
      were metastatic tumors, 03 were hemangiomas and 01 was hepatic adenoma. Doppler
      sonographic findings were then correlated, case by case, with final diagnosis-
      either pathologically by USG guided Fine-needle aspiration or by other imaging
      modalities (e.g., CT scan and RBC liver scan for hepatic hemangioma). The RI
      value of hepatocellular carcinoma was 0.69+/-0.096 and in metastatic tumors
      0.73+/-0.079. The results showed no significant difference between the RI of
      hepatocellular carcinomas and metastatic liver tumors but it was significantly
      higher than benign lesions (p<0.05). RI of hemangiomas was 0.49+/-0.64 and in one
      hepatic adenoma was 0.65. When RI was <0.6 for benign liver tumors and >=0.6 for
      malignant tumors we calculated a sensitivity of 89.14%, specificity of 66.7%,
      accuracy of 85.71% positive predictive value of 97.62% and negative predictive
      value of 28.57% in differentiating benign and malignant tumors. Thirty four of
      46(73.9%) malignant lesions had intratumoral flow and 25% of benign lesions also
      showed intratumoral flow. The difference of intratumoral flow between malignant
      and benign lesions was significant (p<0.01). Two of 4 benign lesions (50%) had
      peritumoral vascularity where 6% of the malignant tumors showed peritumoral
      vascularity. In conclusion, combined studies of the type of intra-and peri
      tumoral flow signals in CDFI and the parameter of RI would be more helpful in the
      differential diagnosis of benign and malignant liver tumors. 

PMID- 24584371
TI  - Serum magnesium status among acute myocardial infarction patients in Bangladesh.
AB  - This case control cross sectional study was carried out in the Department of
      Biochemistry, Mymensingh Medical College in collaboration with Cardiology
      Department of Mymensingh Medical College Hospital, Mymensingh during the period
      of July 2004 to June 2005. The aim of the study was to explore the status of
      serum magnesium among acute myocardial infarction (AMI) patients as a means to
      monitor the possibility of management of these patients. A total of 100 subjects
      were selected and were grouped as Group I (50 healthy control subjects) and Group
      II (50 subjects of AMI Cases). Serum magnesium was estimated by colorimetric
      method from each sample. Statistical analysis was done by using SPSS windows
      package. Among the groups, mean+/-SD (Standard Deviation) of Group I and Group II
      serum magnesium were 2.16+/-0.25 and 1.71+/-0.17mg/dl respectively. By comparing
      Group I with Group II highly significant difference were found in case of serum
      magnesium (p<0.001). It is evident from the study that serum magnesium level
      significantly decreases among acute myocardial infarction patients in Bangladesh.

PMID- 24584372
TI  - Maternal smokeless tobacco use and adverse pregnancy outcome.
AB  - This study was conducted to determine the association between prolonged smokeless
      tobacco (ST) use for more than 5 years by mothers and pregnancy outcome. It was a
      retrospective cohort study done on department of paediatrics and department of
      gynecology & obstetrics, Dhaka Medical College Hospital, Dhaka from January 2009
      to December 2010. A total of 340 mother-neonate pairs were included in the study.
      A total of 170 mothers using smokeless tobacco for more than 5 years and their
      recently delivered newborn infants (mother-neonate pair) were enrolled as cases
      and 170 mother-neonate pairs without history of taking ST as controls. Frequency
      of spontaneous abortion, stillbirth, preterm delivery and LBW baby in case &
      control groups was assessed. Smokeless tobacco used by mothers for >5 years had
      significant association with spontaneous abortion (p<0.01), stillbirth (p<0.01),
      preterm delivery (p<0.001) & LBW baby (p<0.001) and carries a risk of having
      spontaneous abortion, stillbirth, preterm delivery & LBW 2.2 times, 2.1 times,
      2.9 times & 3.3 times respectively more than non users of smokeless tobacco. It
      can be concluded that prolonged use of smokeless tobacco for more than 5 years is
      significantly associated with spontaneous abortion, stillbirth, preterm delivery
      and LBW baby. 

PMID- 24584373
TI  - Changing trends in incidence and indications of caesarean section.
AB  - Caesarean section is most frequently performed major operation in obstetrics. The
      rate of caesarean section has been increasing both in developed and developing
      countries in the past decade. This study was done to find out the change of
      sociodemographic condition of respondents, identify the different types & rate of
      caesarean section indications, the outcome of different indications, estimate the
      rate of caesarean section proportion of the elective & emergency indications and
      evaluate the complications of caesarean sections. This is a cross-sectional study
      of randomly selected 130 cases of lower caesarean section done at Sir Salimullah
      Medical College & Mitford Hospital, Dhaka from March 2006 to August 2006. In this
      study 80(61.5%) cases underwent emergency caesarean section and in 50(38.5%)
      cases elective caesarean section had done. Among indications of caesarean section
      repeat section scores the top of the list. No maternal mortality case recorded in
      this study. This study shows high incidence of caesarean section which does not
      reflect the picture of total population of Bangladesh. 

PMID- 24584374
TI  - Precipitating factor of seizure in epilepsy: experience in a tertiary care
      hospital.
AB  - Patients with epilepsy experience recurrent, unprovoked seizures. In most of the
      cases seizure occurs spontaneously, but there may be association with various
      triggers. These triggers may act as seizure precipitating factors (SPFs). This
      study was done to find out the most common SPFs and their relationship to
      different types epileptic patients attending a tertiary care hospital in
      Bangladesh. This cross sectional study was carried out in specialized epilepsy
      weekly outdoor clinic and Medicine outpatient department (OPD) of Dhaka Medical
      College Hospital from January 2008 to July 2011, which included 1168 epilepsy
      patients. All patients attending the clinic were included in the study. Epilepsy
      syndromes were broadly classified into four categories using the classification
      system of international league against epilepsy (ILAE) namely, generalized
      epilepsy (GE), localization related epilepsy (LRE), symptomatic and unclassified.
      Each patient was evaluated and classified by consultant neurologist. All
      participants were interviewed through a predesigned close ended questionnaire
      that included a long list of 30 precipitating factors. Among all the patients
      71.5% were male, with most common age group 11-20 years (36.8%). About 62% could
      indentify at least one precipitator. Excitation (25.2%) was the most common SPF
      reported by patients followed by emotional stress in 17.7%. Fever precipitated
      seizure in 16.4% of the subjects. A good number of them (15.5%) noticed that
      whenever there was sleep deprivation, they had an attack of epilepsy. However,
      drug withdrawal, playing outside and head trauma were also common among the
      patients, about 11.7%, 11.3% and 8.4% respectively. Most of the patients can
      identify their seizure precipitant and clustering of many SPFs suggests a common
      patho-physiologic mechanism for these triggers. Excitation, sleep deprivation,
      fever, watching television and head trauma showed a strong association with
      generalized epilepsy. Patients with seizure disorder should be evaluated for
      presence of SPFs, because identification of these might help in proper management
      of epilepsy. 

PMID- 24584375
TI  - Chlamydia trachomatis IgM seropositivity during pregnancy and assessment of its
      risk factors.
AB  - The study was undertaken to determine socio-demographic and reproductive risk
      factors associated with Chlamydia trachomaties IgM seropositivity during
      pregnancy. This cross sectional comparative study was carried out in the
      obstetrics outdoor of Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka,
      Bangladesh in collaboration with the department of Virology between the periods
      from July 2007 to December 2008. Pregnant women at their first visit to the
      hospital were approached consecutively and asked to complete a questionnaire and
      2cc blood was collected from each subject for Chlamydia trachomatis IgM antibody
      testing using ELISA method. The study population was divided into two groups
      according to the presence and absence of serum Chlamydia trachomatis IgM
      antibody. Finally socio-demographic and reproductive risk factors were compared
      between the groups. Among 172 women the sero-prevalence of Chlamydia IgM was 41%.
      The multiple logistic regression model (step wise) finally extracted for
      characteristics correlated with seropositivity. Ten years or less (<=SSC)
      education (OR 2.6 95% CI 1.1to 5.9), history of adverse pregnancy outcome (OR 2.8
      95% CI 1.2 to 6.5) and multiple sex partner of husband (OR 4.1 95% CI 1.2 to
      14.8) were associated with chlamydia infection. The use of condom (OR 0.28 95% CI
      0.12 to 0.63) was associated with decreased risk of infection. Chlamydia
      trachomatis infection during pregnancy is associated with risk factors on the
      basis of which selective screening can be done. 

PMID- 24584376
TI  - Outcome of single-stage transanal endorectal pull through for short segment
      Hirschsprung's disease in neonates and infants.
AB  - Hirschsprung's disease (HD) is developmental disorder of the enteric nervous
      system. Diagnosis can be confirmed by rectal biopsy. The surgical management of
      HD includes so many procedures. The purpose of this study was to evaluate the out
      come of single-stage transanal endorectal pull-through operation for short
      segment HD in neonates and infants. This prospective study was carried out in the
      Department of Pediatric Surgery, Dhaka Shishu (Children) Hospital, Dhaka,
      Bangladesh during the period from January 2004 to December 2009. The study
      included neonates & infants (age 1 day to 1 year) of both sex, who were
      clinically suspected and biopsy proven HD with barium enema suggesting
      rectosigmoid HD. We excluded patients with short segment HD who had associated
      anomalies, and with hugely dilated proximal colon, operated cases with less than
      6 months' follow up. During study period, single-stage transanal endorectal pull
      through (TEP) operation done in 68 neonates and infants patients (8 excluded) of
      short segment HD. The mean operative time, postoperative hospital stay, followed
      up time were 120 minutes, 7.94 days and 12 months respectively. Transeverse
      colostomy was needed in 4 patients because of anastomotic leakage and they were
      complicated with anastomotic stenosis, however managed by progressive dilatation.
      Overall parents' satisfaction was achieved. Single-stage primary transnanl
      endorectal pull-through for short segment HD is feasible in neonates and infants.
      It preserves all the advantages of minimally invasive surgery. TEP is a better
      option in terms of comfort, operative success, postoperative morbidity, cosmetic
      appearance and parents' satisfaction. 

PMID- 24584377
TI  - Surgical management of rectourethral fistula in different situations.
AB  - This study was done to see the outcome of repair of rectourethral fistula (RUF)
      in different situations between 2002 and 2009 in Chittagong and Dhaka Medical
      College Hospitals. We prospectively reviewed the records of all the patients who
      developed rectourethral fistula. Total 18 patients were included and in all cases
      faecal and urinary diversion was done preoperatively. In 4 patients fistulas size
      was <1cm where spontaneous closure of RUF occured after 6 months of diversion. In
      8 patients repair of fistula was done through the perineal approach where
      excision of fistulas tract with anastomotic urethroplasty and repair of rectal
      wound was done. Out of these 8 patients tunica vaginalis flap was applied in 3
      and dartos pedicle flap in 5 cases, in the remaining 6 patients transrectal York
      Mason repair was done. Out of 6 patients of York-Mason repair, one developed
      recurrent fistula - which underwent repair with a graft through the perineal
      approach later on with good result. No patient developed urinary or faecal
      incontinence. In 2 patients leakage of urine was noted in post operative days in
      the perineal wound and catheter was kept for 3 weeks more. No one had erectile
      dysfunction. Both faecal & urinary diversion adds benefit to the outcome of the
      rectourethral fistula. Transrectal York-Mason repair is easier to do with less
      morbidity and complication while perineal approach with graft interposition may
      be done in cases where anastomotic urethroplasty is needed along with fistula
      repair. 

PMID- 24584378
TI  - Clinical, biochemical, virological and sonographic profile of incidentally
      detected asymptomatic HBsAg positive subjects, in Bangladesh.
AB  - Chronic hepatitis B virus (HBV) is known to be the significant cause of Liver
      related morbidity and mortality, affecting 400 million people worldwide and a
      major public health problem in Bangladesh where carrier rates of HBV infection
      varies from 7.5 to 10%. In Bangladesh prevalence of asymptomatic HBV infection
      and incidentally detected HBsAg positive subjects were not well studied. The aim
      of this study is to evaluate the disease activity, replicative status of the
      virus and to find out the stages of chronic liver disease among incidentally
      detected asymptomatic HBsAg positive Bangladeshi subjects. Two hundred (200)
      incidentally detected healthy HBsAg positive subject were evaluated clinically,
      biochemically, serologically and ultrasonographically from January 2004 to June
      2008. HBeAg was found positive in 17(8.5%), anti-HBe was positive in 174(87%),
      raised serum ALT (>45iu/L) in 45(22.5%), prothrombine time (PT) >3 sec of control
      in 33(16.5%). Ultrasonography showed coarse hepatic echotexture in 13(6.5%).
      Evidence of active viral replication and signs of chronic liver disease were
      observed among incidentally detected healthy HBsAg positive subjects. Such
      individuals should be followed up at regular interval to evaluate the replicative
      status of the virus and disease activity so that appropriate measures could be
      initiated in time. 

PMID- 24584379
TI  - Sonographic evaluation of thyroiditis with color flow study.
AB  - This cross sectional study was carried out in the Department of Radiology and
      Imaging, Bangabandhu Sheikh Mujib Medical University, Bangladesh in collaboration
      with the Department of Endocrinology and Department of Histopathology of the same
      hospital during the period of March 2007 to February 2008 to determine efficacy
      of ultrasonogram in the evaluation of thyroiditis and to compare its results with
      color flow Doppler study. For this purpose, a total of 50 patients having
      clinical suspicion of thyroiditis were enrolled in this study. Ultrasound and
      color Doppler were done in all these patients. Then all patients underwent for
      FNAC in the Histopathology department. Correlation between sonographic diagnosis
      and histopathological diagnosis were observed. Out of these 50 patients 10(20%)
      were male and 40 (80%) were female with age ranging from 12 to 50 years, highest
      between 21 to 30 years. The mean age of the patients was 30.42+/-9.57 years. On
      unltrasonographic findings of thyroid gland 42.0% patients had regular and 58.0%
      had irregular margin. Seventy percent had fibrosis, 14.0% had feature of
      necrosis, 48.0% had lymphadenopathy. Out of all patients 6.0% had normal
      echogenic feature, 16.0% had increased and 78.0% decreased echogeneic feature.
      Twelve percent (12.0%) patients had homogeneous and 88.0% had heterogeneous
      pattern of echogenecity. Thirty eight percent (38%) patients had focal nodules.
      Sixty percent (60.0%) patients had focal swelling and 40.0% had diffuse swelling.
      On color flow Doppler 28.0% had normal, 38.0% had increased and 34.0% decreased
      vascular flow pattern. USG reports revealed that 48.0% had thyromegaly, 36.0% had
      thyroid nodule, 10.0% had multinodular goiter and 6.0% had thyroid abscess. FNAC
      diagnosis revealed that 34.0% patients had Hashimoto's thyroiditis, 24.0% had
      lymphocytic thyroiditis, 18.0% had granulomatous thyroiditis, 6.0% had abscess,
      8.0% had goitre and 10.0% nonspecific. USG and CFD are recommended modalities for
      the diagnosis of thyroiditis as these cost-effective and non invasive procedures.

PMID- 24584380
TI  - Ultrasonographic evaluation of breast mass.
AB  - Breast cancer is the second most common cause of cancer-related mortality among
      women. The aim of the present study is to investigate the diagnostic accuracy of
      ultrasonography in correlation with histopathology in suspected patients of
      breast mass. In this cross-sectional study, ultrasonography and histopathology
      was done on 50 clinically suspected patients of breast mass in the Department of
      Radiology and Imaging Mymensingh Medical College Hospital, Mymensingh from 1st
      April 2008 to 30th March 2009 for the period of one year. Women of all ages were
      included in the study. Findings of USG and histopathology were correlated. In
      diagnosis of malignant mass by USG, 32(64%) of cases were diagnosed as malignant
      and 18(36%) cases as other than malignant. Here 31(86.1%) of sonographically
      diagnosed malignant lesions were also proved as malignant lesion by
      histopathologically and 1(7.1%) other than malignant. Out of 18 sonographically
      diagnosed cases of other than malignant lesions 13(92.9%) were proved
      histopathologically and 5(13.9%) did not match with sonographic findings as other
      than normal. USG, in diagnosis of malignant lesion, sensitivity was 86.1%,
      specificity 92.9%, positive predictive value (PPV) (96.6%), negative predictive
      value 72.2% and accuracy was 88.0% and comparable to other study. In the
      conclusion this study permits to conclude that ultrasonography has significant
      sensitivity, specificity, accuracy, positive predictive value and negative
      predictive value in the diagnosis of both benign and malignant breast mass. 

PMID- 24584381
TI  - Bacteriology and antibiotic sensitivity patterns of urinary tract infections in a
      tertiary hospital in Bangladesh.
AB  - Urinary tract infection (UTI) is common bacterial infection in mankind. The
      changing antimicrobial sensitivity in UTI demands use of appropriate antibiotics.
      This prospective study was performed in Comilla Medical Collage during the period
      of January 2011 to December 2011. Five hundred and fifty one urine specimens from
      clinically suspected UTI patients were examined by Semi quantitative culture
      method and their antimicrobial sensitivity patterns were determined by disc
      diffusion technique. The study was designed to isolate and identify the nature of
      bacteria in UTI with their sensitivity pattern to common antibiotics. Of the 551
      tested sample 131 samples showed growth of pathogens among which the most
      prevalent were E. coli 98(75%) followed by Klebsiella pneumonia 14(10.7%) and
      Enterococcus 8(6%). The majority 96(73.3%) of the isolates were from female while
      the remaining were from male and this sex difference was statistically
      significant (p<0.001). Imipenem, meropenem, amikacin, nitrofurantoin, gentamycin,
      mecillinum and amoxyclav are found to be effective against 76-100% of the
      uropathogens. Most powerful antibiotics in our study were imipenem, meropenem,
      amikacin and nitrofurantoin which show their efficacy against 91-100% isolates.
      In more than 60% case shows their resistance against amoxycillin, nalidexic acid,
      cefixime, ciprofloxacin, cotrimoxazole and cephalosporins which raises the
      question regarding rationality to empirically use of these antibiotics in UTI
      with out culture and sensitivity reports. 

PMID- 24584382
TI  - Comparative efficacy and safety of trimebutine versus mebeverine in the treatment
      of irritable bowel syndrome.
AB  - Irritable bowel syndrome (IBS) is a functional disorder characterized by chronic
      or recurrent abdominal pain or discomfort with bowel disturbances. This
      prospective, randomized clinical trial has been conducted on IBS patients, using
      trimebutine and Mebeverine in separate group in parallel design to compare the
      efficacy and safety of Trimebutine 100mg twice daily with mebeverine 135mg twice
      daily. Patients of 15 to 60 years old and both sexes were included from the out
      patient department (OPD) of gastroenterology, Bangabandhu Sheikh Mujib Medical
      University (BSMMU) from June 2010 to December 2011. A validated IBS-QOL
      instrument consisted of 34 questions used to assess improvement of quality of
      life before and after treatment. A total of 140 patients were enrolled in this
      study. Eighteen patients dropped out. One hundred twenty two patients completed
      the trial. In this study at the end of 6 weeks therapy, improvement of symptoms
      was statistically significant. However, differences of improvement between the
      two groups in relieving various symptoms were not statistically significant. Mean
      QOL score before treatment was 103 in Trimebutine group and 106 in Mebeverine
      group. After 6 weeks of treatment mean QOL score was 82 in Trimebutine group and
      95 in Mebeverine group indicating improvement in both groups was statistically
      significant. The difference between the two groups was also significant. No
      worsening of symptoms and no side effects of the therapeutic agents was observed
      in any patient during the trial. 

PMID- 24584383
TI  - Lipid profile in women receiving depot medroxyprogesteron acetate as
      contraceptive.
AB  - The study was conducted to estimate the serum lipid levels in women using depot
      medroxyprogesterone acetate (DMPA). A total of 90 Bangladeshi married women of
      age group 15-40 years attending the Model Family Planning Clinic, Mymensingh
      Medical College Hospital, Mymensingh, from July 2010 to June 2011. Patients were
      classified into three groups comprising those using the drug for 3 months (n=30),
      1 year (n=30), and 2 years (n=30), respectively, compared to a control group
      (n=30) of married non-hormonally treated women of similar ages. Their age,
      weight, height, BP and BMI were recorded; all the subjects were clinically
      examined. Blood samples were collected for biochemical assay of serum lipid
      profiling parameters, such as total cholesterol, HDL-C, TAG and LDL-C. Data were
      collected and processed according to the design and objectives of the study. A
      significant (p<0.01) decrease in serum total cholesterol was observed up to 1
      year of using DMPA, but a sharp increase was observed in 2 years group. Likewise
      total cholesterol, HDL-C was significantly (p<0.01) decreased in the 1 year group
      and rapidly increased in the 2 years group. A significant (p<0.01) reduction in
      TAG level was observed throughout the study tenure when compared with control
      group. No significant (p>0.05) difference in LDL-C level was observed among the
      treatment groups. The study concludes that DMPA induced significant alterations
      in lipid profiling parameters of the studied population and prolong use does not
      have risk of atherosclerosis; however, further study with a larger sample size is
      suggested for a general recommendation. 

PMID- 24584384
TI  - Regional metastasis in supraglottic and glottic carcinoma of larynx.
AB  - This cross sectional study was conducted in Sir Salimullah Medical College
      Hospital, Mitford and Dhaka Medical College Hospital, Dhaka, Bangladesh from
      January 2009 to December 2009 by purposive sampling method. Among the 50 cases,
      involvement of supraglottic (72%) region is significantly higher than glottic
      (28%) region. Affected peoples are mainly male and mean age was 58.1+/-10.4
      years. Frequency of regional metastasis of supraglottic carcinoma (47.22%) was
      higher than glottic carcinoma (7.14%). Most of the lymphnode involvement was at
      level-II to IV. Most of the patients presented at stage-I & stage-II. 

PMID- 24584385
TI  - Influence of body mass index on low back pain.
AB  - Low back pain (LBP) is a common problem affecting 70% of the population in the
      developed countries and prevalence is also increasing in the developing
      countries. We conducted a clinic based cross-sectional study in the city of Dhaka
      and Chittagong during the period of January 2009 to December 2011. Participants
      (n=357) were interviewed and examined through a structured questionnaire after a
      non purposive sampling to explore the influence of body mass index (BMI) on LBP.
      BMI was assessed by the equation weight (Kg)/hight2 (m2) and LBP was assessed by
      modified visual analogue scale. Association between LBP and BMI was tested by Chi
      square test. Among 357 patients the incidence of LBP was common in the age group
      between 40-59 years and it was 172(48.17%) followed by 60-79, 20-39 and >=80
      years group with 21.29%, 17.65% and 12.89% respectively. Female presented more
      with LBP, i.e. 196(54.91%) than the male 161(45.09%). The more study population
      was found to have BMI within normal range, i.e. 167(46.78%). This was followed by
      overweight group which amounted 137(38.37%) while the obese group was the least,
      i.e. 53(14.85%). Maximum study population presented with severe LBP which
      amounted 140(39.22%) while others presented with moderate and mild LBP and
      amounting 118(33.05%) and 99(27.73%) respectively. Among the normal BMI group
      most patient presented with mild pain (n=82) followed by moderate (n=55) and
      severe (n=30) pain. Participants with overweight presents with severe pain mostly
      (n=58) but obese participants presented with severe low back pain (n=25).
      Statistically the association of LBP with BMI was found to be highly significant
      (p<0.0001). In this study, 137(46.78%) participants of normal BMI presented with
      LBP but majorities (n=82) presented with mild LBP and overweight and obese
      participants mostly presented with severe LBP. On the basis of these findings,
      careful evaluation of risk factors and deliberate assessment of the therapeutic
      as well as preventive measure for the management of patient of LBP is highly
      recommended. 

PMID- 24584386
TI  - Laparoscopic assisted appendicectomy in District Hospital, Joypurhat, Bangladesh.
AB  - "Laparoscopic assisted appendicectomy" refers to visualization of abdominal
      cavity, identification of appendix, drawing the appendix out through the port
      wound and appendicectomy. The objective of this study is to evaluate the outcome
      of the procedure of laparoscopic assisted appendicectomy. In this prospective
      study patients with appendicitis were randomly selected for laparoscopic assisted
      appendicectomy from August 2007 to February 2009 in the Department of Surgery,
      Modernized District Hospital, Joypurhat, Bangladesh. Out of 73 patients
      Laparoscopic assisted appendicectomy was performed successfully in 95.89% cases
      and conversion rate was 4.11%. Male to female ratio was almost 1:2 with mean+/-SD
      age 18.62+/-9.16 years. The wound infection rate was 8.2% and urinary retention
      2.7%. Early postoperative feeding was started within 24 hours in 86.3% cases and
      mean duration of hospital stay was 2 days in 76.71% patients. More than 82%
      returned to their home and started social activities within 5 days. Duration of
      surgery was almost similar in emergency and interval appendicectomy group
      (19.35+/-10.13 vs. 23.66+/-9.43) minutes. Postoperative morbidity in emergency
      appendicectomy group showed significantly higher morbidity than interval
      appendicectomy group (p=0.003). This study indicates that the laparoscopic
      assisted appendicectomy is feasible for the majority of the patients with
      appendicitis in both emergency and interval settings. It reduces the operative
      time, shortens hospital stay and helps in early resumption of normal activities
      with good cosmetic outcome and patients' satisfaction. 

PMID- 24584387
TI  - Perception of medical students about pharmacology and scope of improvement.
AB  - Pharmacology is a subject taught in the medical curriculum in India over a period
      of one and half years along with pathology, microbiology and forensic medicine.
      The present study was planned to know the opinion of medical students regarding
      pharmacology and to assess the proposed teaching schedule and methods of teaching
      pharmacology. The study was conducted in a private medical college in eastern
      India among the medical undergraduate students in 5th semester. Total 74 students
      participated in the study. A pre-designed, pre-tested, semi-structured
      questionnaire was given to the students and data was collected after one hour.
      Collected data was compiled, tabulated and analyzed in SPSS (version 16.0). The
      subject was perceived as interesting and useful by majority of students and most
      of them were in opinion to integrate pharmacology with the clinical subjects.
      Lecture in whole class was the most preferred teaching method according to the
      students and teaching with chalk and board they preferred most. Rational use of
      medicine, clinical trial, pediatric and geriatric pharmacology are the important
      topics the students felt to be included in the curriculum. Regular assessment of
      teaching methods by the students and taking suggestions from the students about
      improving the teaching method and redesigning the curriculum can help a lot in
      improving the learning capacity of the medical students and that will give
      benefit for the society as a whole. 

PMID- 24584388
TI  - Urinary tuberculosis presented as isolated bladder lesion - a case report.
AB  - Extra-pulmonary Tuberculosis (EPTB) may affect all organs of the body with varied
      presentations. Genitourinary tuberculosis (GUTB) carries importance for its
      morbidity, though it is an uncommon form of TB. A widow of 45 years was admitted
      with several episodes of painless haematuria and recently developed urinary
      incontinence. Diagnosis of urinary bladder tuberculosis was made only by
      histopathology from bladder lesion with supportive evidence of few nonspecific
      constitutional symptoms and positive family history of pulmonary tuberculosis
      (PTB) and persistent sterile pyuria. Upper urinary tract involvement was not
      found. Category 1 anti-TB treatment was started. With this treatment recovery of
      the patient is satisfactory and symptoms are disappearing except for the
      incontinence. Urinary tuberculosis should be ruled out in a case of painless
      haematuria, repeated sterile pyuria. 

PMID- 24584389
TI  - Duodenal carcinoid tumor - a case report.
AB  - Carcinoid tumors are well differentiated neuroendochrine tumors which most
      frequently involve the gastrointestinal tract; however duodenal carcinoid tumors
      are rare. They can present with various clinical symptoms and are difficult to
      diagnose. A 52 years old lady presented with the symptoms of recurrent upper
      abdominal pain, burning sensation of whole body and passage of loose stool. On
      endoscopy of upper GIT, there was a duodenal polyp. Polyp was removed by
      endoscopic resection and tissue was taken for biopsy. Histological findings of
      biopsy specimen shows carcinoid tumor. As duodenal carcinoid tumor is a rare
      presentation so we are going to present this case in this article. 

PMID- 24584391
TI  - A giant hepatic cyst.
AB  - Liver cysts occur in approximately 5% of the population. However, only about 5%
      of these patients ever develop symptoms. In general, cysts are thin-walled
      structures that contain fluid. Most cysts are single, although some patients may
      have several. Here we report a case of a giant hepatic cyst in a 50 year old
      female who was admitted in our Hospital for right upper quadrant pain and
      abdominal lump. She was thoroughly investigated with ultrasonography, and
      computerized tomography scan of the abdomen along with other supportive
      investigations, and was diagnosed as having a 30*25cm cyst in the right lobe of
      the liver. Exploratory laparotomy and partial cystectomy with drainage &
      marsupialization were performed in the patient.

PMID- 24584390
TI  - Silent killer HCV and its early detection can stop its propagation: a case study.
AB  - Though regular blood transfusion improves the overall survival of patients with
      beta-thalassemia which is one of the most common genetic diseases in the world,
      carries a definite risk of infection with blood-borne viruses. World Health
      Organization (WHO) reported that there is about 3% beta thalassemia carrier and
      more than two thousand thalassemic children are born every year in Bangladesh.
      Master Akib of age 15 years was the known case of Beta Thalassemia taking blood
      from his 3rd Birth Day from Mymensingh Combined Military Hospital, Bangladesh.
      Day care centre of Transfusion Medicine Department of Mymensingh Medical College
      Hospital started HBV, HCV, HIV screening of Thalassemic patient from 1st July,
      2012. After screening of his blood, we found his blood contains HCV which is 3-4
      times repeated positive with three other companies' reagent (rapid immuno
      chromatographic assay) and result is confirmed. His treatment started and
      continues for 24 weeks and after 24 weeks, to monitor treatment response, his
      blood again test for Serum HCV-RNA which was not detected. Now Master Akib free
      from HCV infection and HCV diagnose accidentally because it remain silent for
      long time. We recommend that in public sector hospitals and health care units
      ELISA should be preferred for anti-HCV detection over ICT. 

PMID- 24584392
TI  - Moebius syndrome with Taussig-Bing anomaly.
AB  - We report a 6 years old male child, presented with difficulty in swallowing,
      crying and smiling from early infancy and recurrent episodes of cyanosis on
      exertion for about 2 years. He had facial dysmorphism, clubbing and polydactyly
      and right sided lower motor neuron type of facial nerve palsy. On examination and
      relevant investigations findings were consistent with Moebius syndrome and
      Taussig-Bing anomaly. Moebius syndrome comprises of congenital facial nerve palsy
      with or without palsy of the other cranial nerves and the associated organ system
      malformations. Taussig-Bing anomaly is a rare congenital heart malformation
      consisting of a transposed aorta, a large pulmonary artery which arises primarily
      from the right ventricle and ventricular septal defect. Simultaneous occurrence
      of Moebius syndrome and Taussig-Bing anomaly has not yet been reported in the
      past. 

PMID- 24584393
TI  - Neu-Laxova syndrome: a case report.
AB  - Neu-Laxova syndrome (NLS) is a rare lethal syndrome found in both consanguinous
      and non-consanguinous couple. This is characterized by terrible face with unusual
      craniofacial appearance with exophthalmos, spectrum of central nervous system
      malformation, like microcaphaly, hypoplastic cerebellum, cleft lip/palate,
      ichthyosis and oedema. The diagnosis is made on the basis of clinical parameter.
      We report a 4 hour old male term newborn with IUGR of Neu-Laxova syndrome
      presented with anencephaly, rudimentary cerebellum, exophthalmos of right eye,
      bilateral cleft lip and palate and cryptorchidism. Anencephaly and cryptorchidism
      are two recently reported findings of NLS. We are presenting this case in
      addition from Bangladesh to lend further support to those two new findings as
      component of Neu-Laxova syndrome. Outcome of this syndrome is not good. Most of
      the patients are died of infection within hours to days. 

PMID- 24584394
TI  - Synovial sarcoma of neck mimicking thyroid carcinoma.
AB  - Synovial sarcoma (SS) in the neck is a very rare condition. Here we report a case
      of poorly differentiated synovial sarcoma in the neck of a 20 years old male
      patient presented with painless swelling in thyroid gland region. Initially he
      was diagnosed as thyroid mass clinically, by imaging and also by FNAC (Both in
      Bangladesh & India). But at surgery, it revealed paraoesophageal soft tissue
      tumor and subsequent histopathology showed synovial sarcoma. In young patient
      with neck swelling, the possibility of synovial sarcoma should be considered. As
      it does not have overall good prognosis, early detection and regular follow up is
      necessary. 

PMID- 24584395
TI  - Campylobacteriosis - an overview.
AB  - Campylobacteriosis is a collective term, used for infectious, emerging foodborne
      disease caused by Campylobacter species comprising Gram negative, curved, and
      microaerophilic pathogens. The true incidence of human campylobacteriosis is
      unknown for most countries of the world including Bangladesh. But
      campylobacteriosis is not uncommon in our country. Due to its increasing
      incidence in many countries of the world, it is an important issue now a day.
      Animals such as birds are the main sources of infection. Farm animals such as
      cattle, poultry are commonly infected from such sources and raw milk, undercooked
      or poorly handled meat becomes contaminated. Transmission of campylobacteriosis
      to human occurs through consumption of infected, unpasteurized animal milk and
      milk products, undercooked poultry and through contaminated drinking water.
      Contact with contaminated poultry, livestock or household pets, especially
      puppies, can also cause disease. Due to variability of clinical features and
      limited availability of laboratory facilities, the disease remains largely under
      reported. Early and specific diagnosis is important to ensure a favourable
      outcome regarding this food borne disease. Antibiotic treatment is controversial,
      and has only a benefit on the duration of symptoms. Campylobacter infections can
      be prevented by some simple hygienic food handling practices. 

PMID- 24584396
TI  - Acne vulgaris related to androgens - a review.
AB  - Sebum production is stimulated by androgens and is the key in the development of
      acne vulgaris. Several investigators have looked for direct relationships between
      serum androgen levels, sebum secretion rate and the presence of acne. The
      presence of acne in prepubertal girls and sebum production in both sexes
      correlate with serum dehydroepiandrosterone sulfate (DHEAS) levels. Although
      increased serum androgen levels correlate with the presence of severe nodular
      acne in men and women, these levels are often within the normal range in mild to
      moderate acne. This raises the question of whether there is an increased local
      production of androgens within the sebaceous gland of patients with acne vulgaris
      that leads to increased sebum secretion. 

PMID- 24584397
TI  - Dieulafoy's lesion: an overview.
AB  - Dieulafoy's lesion accounts for 1-5.8% of cases of acute upper GI bleeding. The
      two largest retrospective series, both from North America, found Dieulafoy's
      lesion as the source of hemorrhage in 1.9% and 1.2% of all endoscopies performed
      for acute GI bleeding. In the prospective study of Chung et al., Dieulafoy's
      Lesion was found in 3.4% of all patients with acute GI bleeding referred to their
      unit. The Dieulafoy's Lesion accounted for up to 40% of all causes of nonvariceal
      upper GI bleeding not caused by gastric or duodenal ulceration or esophageal
      varices in the prospective study of Matsui et al. In the study of Schmulewitz and
      Bailli, colonic Dieulafoy's Lesion were only found in 0.09% of all colonoscopies
      performed for lower GI bleeding. The actual incidence of both upper and lower GI
      bleeding from Dieulafoy's Lesion is likely higher than estimated because the
      diagnosis remains difficult. Recent advances in endoscopy have led to an
      increased detection of Dieulafoy's lesions. Initial GI endoscopy is effective in
      diagnosing up to 70% of patients. Several endoscopies may be required with 6% of
      patients, requiring three or more to establish the diagnosis. Angiography and/or
      red cell scanning can be used when endoscopy fails to diagnose a doubtful case.
      There is no definite unique policy for the treatment of Dieulafoy's lesions.
      Therapeutic endoscopy remains the first line of treatment option for controlling
      the bleeding while angiography is considered as a valuable alternative. Surgical
      intervention is kept for failure cases where it should be guided by preoperative
      localization. The mortality rate has decreased dramatically from 80% to 8.6% in
      recent times due to advancement in both diagnostic and therapeutic tools. 

PMID- 24584398
TI  - Neurologic manifestations, diagnosis and management of Wilson's disease in
      children - an update.
AB  - Wilson's disease (WD) is a genetic disorder of copper (Cu) metabolism. It is a
      progressive hepatolenticular degenerative disease due to toxic accumulation of
      copper in the various tissues particularly in the liver, brain and eyes. The
      neurologic manifestations of Wilson's disease are extremely varied like simple
      behavioral change such as irritability, depression, deterioration of school
      performance to severe form of neurologic presentations like dystonia, dysarthria,
      tremor and gait disturbance. Early diagnosis is possible by history of
      progressive neurologic dysfunction, clinical examination of Kayser Flescher rings
      (K-F rings) in eyes, along with some important investigations like low serum
      ceruloplasmin, high 24 hours urinary excretion of copper, presence of basal
      ganglia lesion in neuro imaging of the brain. Though hepatic copper estimation
      done by liver biopsy is the gold standard, is not available in Bangladesh. Most
      of the neurodegenerative diseases have no specific treatment and worse outcome.
      But it has a specific treatment with life long medication that reduces copper
      absorption or removes the excess copper from the body. Children on therapy must
      be monitored regularly for response, side effects and compliance. The aim of this
      article is to gather update information of neurologic manifestations of Wilson's
      disease and proper management as well to prevent the major neurological
      complications and better out come. 

PMID- 24584399
TI  - Meta-analyses using individual participant data from cardiovascular cohort
      studies in Japan: current status and future directions.
AB  - Meta-analysis of individual participant data (IPD meta-analysis) has several
      advantages over meta-analysis using aggregated published data, including the
      possibility of using statistical methods such as a fine stratification analysis,
      interaction analysis between 2 risk factors, and absolute risk estimation. The
      Evidence for Cardiovascular Prevention from Observational Cohorts in Japan Study
      (EPOCH-JAPAN), which was initiated in 2005, is a collaborative research project
      for IPD meta-analysis and includes 13 participating cohort studies in Japan. We
      generated 2 pooled databases with data on all-cause mortality (n = 199 047) and
      cardiovascular outcomes (n = 90 528) and applied a stratified Cox model to
      account for the different baseline hazards between cohorts. The results of our
      analyses show the age- and sex-specific associations between all-cause and
      cardiovascular disease mortality and established cardiovascular risk factors
      (blood pressure, smoking, total cholesterol, proteinuria, and kidney function).
      During the 9 years of its existence, the results generated by EPOCH-JAPAN have
      had important implications for clinical medicine and public health policy in
      Japan. The project is expected to draw upon new analytical methods such as
      interaction analysis and absolute risk evaluation in the near future. We believe
      that, over the next decade, this project will continue to provide new insights
      that can be applied to research on other Asian populations. 

PMID- 24584400
TI  - Number of sentinel medical institutions needed for estimating prefectural
      incidence in influenza surveillance in Japan.
AB  - BACKGROUND: The sentinel surveillance system in Japan provides estimates of
      nationwide influenza incidence. Although prefectural influenza incidences can be
      estimated using data from the current surveillance system, such estimates may be
      imprecise. METHODS: We calculated the numbers of sentinel medical institutions
      (SMIs) needed in the surveillance system to estimate influenza incidences in
      prefectures, under the assumption that the standard error rates in 75% of
      influenza epidemic cases are less than 10%. Epidemic cases observed in 47
      prefectures during the 2007/2008, 2008/2009, and 2009/2010 seasons, respectively,
      were used. RESULTS: The present total number of SMIs was 6669. With respect to
      current standards, the increases required in prefectures ranged from 0 to 59, and
      the total increase required in the number of SMIs was 1668. CONCLUSIONS: We used
      sentinel surveillance data for Japan to calculate the number of SMIs required to
      estimate influenza incidence in each prefecture.

PMID- 24584406
TI  - Berberine ameliorates severe acute pancreatitis-induced intestinal barrier
      dysfunction via a myosin light chain phosphorylation-dependent pathway.
AB  - Berberine is a traditional drug used to treat gastrointestinal disorders in China
      and has been demonstrated to attenuate intestinal barrier dysfunction in certain
      animal models. However, the effects of berberine on pancreatitis-induced
      intestinal barrier dysfunction are yet to be fully elucidated. This study aimed
      to investigate the effect of berberine pretreatment on the attenuation of
      intestinal barrier dysfunction induced by severe acute pancreatitis (SAP). A
      total of 36 rats were randomly divided into Sham, SAP and SAP plus berberine
      groups. Pancreatitis was induced using retrograde injection of 3% Na-taurocholate
      into the pancreatic duct. Histological examinations of the pancreas were
      performed and intestinal barrier dysfunction was characterized by histological
      measurements and the assessment of serum diamine oxidase activity and endotoxin
      levels. Zonula occludens-1 and occludin mRNA and protein expression, as well as
      myosin light chain (MLC) phosphorylation, were assessed. SAP rat models were
      successfully established. Berberine treatment was found to have no significant
      effect on the histological changes in the pancreas, but was observed to
      ameliorate the intestinal mucosal barrier damage and membrane permeability
      associated with SAP. Although berberine exerted minimal effects on tight junction
      proteins in the ilea of SAP rats, it was observed to significantly inhibit SAP
      induced MLC phosphorylation. To the best of our knowledge, this is the first
      study to demonstrate that berberine attenuates SAP-induced intestinal barrier
      dysfunction in vivo. In addition, this study shows that the effect of berberine
      on intestinal barrier function may be associated with the inhibition of SAP
      induced upregulation of MLC phosphorylation.

PMID- 24584407
TI  - Osmolal gap without anion gap in a 43-year-old man.

PMID- 24584408
TI  - Commentary.

PMID- 24584409
TI  - Commentary.

PMID- 24584410
TI  - Unexpected urine crystals and hematuria.

PMID- 24584411
TI  - Pheochromocytoma: yes or no?

PMID- 24584413
TI  - Summertime at a mountain bamboo grove.

PMID- 24584414
TI  - On gothic cathedrals and contemporary science.

PMID- 24584417
TI  - In situ TEM ion irradiation and implantation effects on Au nanoparticle
      morphologies.
AB  - Energetic heavy and light ion effects on gold nanoparticles were probed by
      irradiating 20 and 60 nm diameter nanoparticles with either 3 MeV Cu(3+) or 10
      keV He(+) ions in situ inside of a transmission electron microscope. Both ion
      species caused sintering, agglomeration, and ablation of the nanoparticles via
      sputtering, although at different rates. 

PMID- 24584418
TI  - On the origin of the substantial stabilisation of the electron-donor 1,3-dithiole
      2-thione-4-carboxyclic acid...I2 and DABCO...I2 complexes.
AB  - The stabilisation energies of the crystal structures of 1,3-dithiole-2-thione-4
      carboxyclic acid...I2 and DABCO...I2 complexes determined by the CCSD(T)/CBS
      method are very large and exceed 8 and 15 kcal mol(-1), respectively. The DFT-D
      method (B97-D3/def2-QZVP) strongly overestimates these stabilisation energies,
      which support the well-known fact that the DFT-D method is not very applicable to
      the study of charge-transfer complexes. On the other hand, the M06-2X/def2-QZVP
      method provides surprisingly reliable energies. A DFT-SAPT analysis has shown
      that a substantial stabilisation of these complexes arises from the charge
      transfer energy included in the induction energy and that the respective
      induction energy is much larger than that of other non-covalently bound
      complexes. The total stabilisation energies of the complexes mentioned as well as
      of those where iodine has been replaced by lighter halogens (Br2 and Cl2) or by
      hetero systems (IF, ICH3, N2) correlate well with the magnitude of the sigma-hole
      (Vs,max value) as well as with the LUMO energy. The nature of the stabilisation
      of all complexes between both electron donors and X2 (X = I, Br, Cl, N) systems
      is explained by the magnitude of the sigma-hole but surprisingly also by the
      values of the electric quadrupole moment of these systems. Evidently, the nature
      of the stabilisation of halogen-bonded complexes between electron donors and
      systems where the first non-zero electric multipole moment is the quadrupole
      moment can be explained not only by the recently introduced concept of the sigma
      hole but also by the classical concept of electric quadrupole moments.

PMID- 24584416
TI  - Phylogenetic and functional analysis of gut microbiota of a fungus-growing higher
      termite: Bacteroidetes from higher termites are a rich source of beta-glucosidase
      genes.
AB  - Fungus-growing termites, their symbiotic fungi, and microbiota inhibiting their
      intestinal tract comprise a highly efficient cellulose-hydrolyzing system;
      however, little is known about the role of gut microbiota in this system. Twelve
      fosmid clones with beta-glucosidase activity were previously obtained by
      functionally screening a metagenomic library of a fungus-growing termite,
      Macrotermes annandalei. Ten contigs containing putative beta-glucosidase genes
      (bgl1-10) were assembled by sequencing data of these fosmid clones. All these
      contigs were binned to Bacteroidetes, and all these beta-glucosidase genes were
      phylogenetically closed to those from Bacteroides or Dysgonomonas. Six out of 10
      beta-glucosidase genes had predicted signal peptides, indicating a transmembrane
      capability of these enzymes to mediate cellulose hydrolysis within the gut of the
      termites. To confirm the activities of these beta-glucosidase genes, three genes
      (bgl5, bgl7, and bgl9) were successfully expressed and purified. The optimal
      temperature and pH of these enzymes largely resembled the environment of the
      host's gut. The gut microbiota composition of the fungus-growing termite was also
      determined by 454 pyrosequencing, showing that Bacteroidetes was the most
      dominant phylum. The diversity and the enzyme properties of beta-glucosidases
      revealed in this study suggested that Bacteroidetes as the major member in fungus
      growing termites contributed to cello-oligomer degradation in cellulose
      hydrolyzing process and represented a rich source for beta-glucosidase genes. 

PMID- 24584415
TI  - A cause for concern: male couples' sexual agreements and their use of substances
      with sex.
AB  - Substance use is strongly associated with HIV risk among gay men. Many gay
      couples establish sexual agreements. However, little is known about gay couples'
      use of substances with sex, and whether substance use is associated with couples'
      agreements. The present study assessed whether gay couples' use of substances
      with sex was associated with their establishment of, type of, and adherence to, a
      sexual agreement. Dyadic data from 275 HIV-negative US gay couples were collected
      online in a nation-wide, cross-sectional study, and analyzed at the couple-level.
      Findings revealed that couples with an established agreement, and a recently
      broken agreement, were more likely to have used amyl nitrates and marijuana with
      sex within their relationship. This same trend was also noted, but for alcohol
      use with sex outside of couples' relationships. Further research is urgently
      needed to examine the fluidity of HIV-negative gay male couples' sexual
      agreements and substance use with sex.

PMID- 24584425
TI  - [Not Available].

PMID- 24584426
TI  - [Not Available].

PMID- 24584427
TI  - [Atrial fibrillation in pacemaker therapy: physiologic versus VVI pacing].
AB  - Recent prospective trials of pacing in atrial fibrillation are inconclusive. A
      substantial suppression of atrial tachyarrhythmias has been observed in patients
      with brady-tachy-syndrome and high rate of paced vs. intrinsic beats. An
      improvement in prognosis, incidence of thromboembolism, rehospitalization and
      improvement in heart failure have been controversally described in different
      trials. The quality of life improves in most studies in physiologic pacing. This
      paper presents a short overview on published and ongoing trials in pacing of
      atrial fibrillation. 

PMID- 24584428
TI  - [Pathophysiology of pacing in patients with atrial fibrillation].
AB  - The limited efficacy of and side effects associated with antiarrhythmic drug
      therapy have led to renewed interest in non-pharmacologic treatment options for
      paroxysmal atrial fibrillation. In addition to catheter ablation of the
      initiating ectopic atrial beats, electrical stimulation of the atrium is a new
      and promising method to reduce the frequency of arrhythmia recurrences. Recent
      studies have confirmed the importance of both the initiating triggers and the
      electrophysiologic substrate for the recurrence and perpetuation, respectively,
      of atrial fibrillation. Bradycardia and pauses, atrial premature beats, and early
      recurrence of atrial fibrillation all seem to play an important role for (re
      )initiation of an episode. Results from single-site atrial pacing in the high
      right atrium have shown a reduction of atrial fibrillation episodes and
      progression into chronic atrial fibrillation in selected groups of patients
      (brady-tachycardia syndrome and vagally induced atrial fibrillation). Therefore,
      specific preventive pacing algorithms (atrial overdrive pacing, rate smoothing or
      rate acceleration after detection of atrial premature beats and termination of a
      mode-switch) and new pacing sites have recently been investigated in order to
      address all of these initiation mechanisms and to increase the efficacy of
      pacing. In studies published so far, the specific pacing algorithms seem to add
      benefit compared to atrial-based demand (AAI or DDD) pacing alone. Finally,
      attempts are being made to terminate recurrences of atrial tachycardia or atrial
      flutter with antitachycardia pacing algorithms in order to avoid progression into
      atrial fibrillation. Based on experimental and clinical evidence, the initial
      phase of the majority of atrial tachyarrhythmia recurrences is not 'leading
      circle reentry'. Most episodes start relatively regular and seem to have an
      excitable gap, allowing capture and pace termination. 

PMID- 24584429
TI  - [Preventive pacing in patients with paroxysmal atrial fibrillation: programming
      and follow-up of patients with dual-chamber pacemakers and triggered preventive
      pacing functions].
AB  - A treatment of patients with paroxysmal atrial fibrillation is the implantation
      of DDDRP pacemakers for preventive pacing. Atrial pacing with the aim for
      preventive pacing of atrial fibrillation can be classified as continuous constant
      pacing with a fixed manually programmed lower atrial pacing rate. The second
      approach is continuous dynamic overdrive pacing realized by new pacing
      algorithms, e.g., Pace Conditioning in the Vitatron DDDRP pacemakers. The third
      approach is discontinuous triggered pacing when specific pacing algorithms are
      activated by trigger events and temporally pace the atrium. The actual
      established indications for preventive pacing are patients with a conventional
      pacing indication and a history of paroxysmal atrial fibrillation. A possible
      indication are patients with a standard indication for cardiac pacing and a high
      risk to develop atrial fibrillation as well as patients with drug-refractory
      atrial fibrillation before AV-node ablation. After pacemaker implantation the
      pacemaker can be programmed individually according to the onsets of atrial
      fibrillation observed in the patient or the patient receives a standard
      programming and subsequently an individual adjustment of the pacing functions.
      The success of preventive pacing should be assessed a each follow-up visit by
      interrogation of the extended diagnostic pacemaker counters. There are at present
      no prospective studies concerning the effects of different pacemaker programming.

PMID- 24584430
TI  - [Alternative pacing sites for the prevention of atrial fibrillation].
AB  - Background The induction of atrial fibrillation depends upon the interaction
      between basic rhythm, ectopic activity, and inter-/intraatrial conduction. In
      pacing therapy, the atrial pacing site may influence the incidence of atrial
      tachyarrhythmias. This review discusses the antiarrhythmic potential of different
      atrial pacing sites. Results Three atrial pacing modes have been evaluated with
      respect to their potential to prevent atrial tachyarrhythmias: biatrial, bifocal
      right atrial, and dedicated unifocal right atrial pacing sites. Biatrial pacing
      aims at shortening the global atrial activation time in patients with interatrial
      conduction block. Observational studies showed a suppression of atrial
      tachyarrhythmias in 1/3 of patients, while a randomized study could not
      demonstrate a significant effect. Bifocal pacing at the high right atrium and
      coronary sinus os showed a higher preventive efficacy than unifocal pacing in a
      single center experience which was partly confirmed by a multicenter trial.
      Atrial septal pacing at the triangle of Koch provides antiarrhythmic effects but
      may be more difficult to reach and limited by oversensing of ventricular far
      field signals. A randomized study found a preventive effect of pacing near
      Bachmann's bundle; this site seems particularly attractive for its easy access
      and low risk of ventricular far-field oversensing. Conclusions In patients with
      an indication for permanent pacing and paroxysmal or persistent atrial
      fibrillation, the atrial pacing site may facilitate maintenance of sinus rhythm.
      While reliable sensing and pacing are prerequisites, particularly high septal
      atrial pacing may provide an additional antiarrhythmic effect at an expenditure
      comparable to conventional atrial pacing sites. 

PMID- 24584431
TI  - [Antitachycardia pacing for atrial tachyarrhythmias].
AB  - Overdrive pacing therapies are well established to treat patients with
      ventricular tachycardia. The main advantage is the quick and painless success
      with a high efficacy. Newer observations show that atrial arrhythmias with short
      cycle lengths (<200ms) can be terminated by painless overdrive pacing therapies
      as well. In the AT500 verification study and in the Jewel AF-trial, 30-60% of all
      treated atrial arrhythmias could be terminated by overdrive pacing. Nevertheless,
      these encouraging results need to be confirmed by additional randomized clinical
      trials. Especially the "hybrid" therapy (overdrive pacing in combination with an
      antiarrhythmic drug therapy) looks promising. 

PMID- 24584432
TI  - [Intra- and interatrial conduction - consequences for electrode placement].
AB  - Background Intra-atrial (IAA) and inter-atrial (IEA) conduction times during
      atrial pacing (P) are determined by conduction characteristics of IAA and IEA
      activation and by the atrial origin of stimulation. It seems that atrial P at
      identical locations can induce different conduction times dependent on the
      quality of the IAA and IEA conduction structures. Purpose of the study The aim of
      this study was to analyze the influence of pacing on normal IAA and IEA
      activation and the p-wave duration (PWD) in a sheep model. Different atrial wall
      contact pacing positions as well as a novel floating pacing configuration
      (BIdirectional MOnophasic ImpulSe: BIMOS; induced partial overlapping of
      electrical fields by splitting a conventional pacing impulse between three
      electrodes) were tested. The influence of pacing on a primary prolonged PWD is
      summarized, using published data. Methods Normal IAA, IEA conduction times and
      PWD: Twenty Merino sheep (4.6+/-0.7 years; 60.1+/-3.6 kg) were studied. EP
      catheters were placed under fluoroscopy close to the His Bundle (HBE), in the
      high right atrium (HRA), in the coronary sinus ostium (Cs-Os), and in the left
      lateral atrium (LLA). A modified single-VDD lead was introduced with the atrial
      ring electrodes floating in the high and mid right atrium. IAA (S/P-HRA, S/P-Cs
      Os, S/P-HBE, S/P-floating), IEA conduction times (S/P-LLA), and P-wave duration
      (PWD) were assessed during intrinsic sinus rhythm (S), during bipolar cathodal P
      during wall contact in the HRA and in the Cs-Os, as well as during floating P
      with BIMOS configuration. Primary prolonged PWD: the influence of different novel
      pacing concepts ("biatrial" P, "dual site" P, "septal" P, "Bachmann bundle" P) on
      primary prolonged PWD were analyzed using data from the literature. Results
      Normal IAA and IEA conduction times and PWD: The mean PWD during S was
      significantly shorter than during HRA- (66.6+/-12.8 ms; vs. 116.2+/-11.1 ms;
      p<0.05) and Cs-Os-pacing (66.6+/-12.8 ms vs. 94.4+/-9.0 ms; p<0.05). Floating
      pacing with BIMOS showed no significant difference to S: 66.6+/-12.8 ms vs.
      85.4+/-8.8 ms (p>0.05). PWD decreased significantly when the pacing protocol was
      changed from HRA pacing to floating pacing with BIMOS. The IEA conduction time
      (S/P-LLA) was also significantly shorter during S than during HRA pacing (34.7+/
      14.7 ms vs. 89.7+/-13.5 ms; p<0.05), Cs-Os pacing (34.7+/-14.7 ms vs. 66.3+/-7.0
      ms; p<0.05), and BIMOS pacing (34.7+/-14.7 ms vs. 61.3+/-12.7 ms; p<0.05).
      Compared to HRA pacing, floating pacing with BIMOS leads to a significant
      reduction of the PWD. Primary prolonged PWD: All new pacing concepts were
      developed primary for pace prevention of atrial arrhythmias. These pacing
      concepts reduce significantly primary prolonged PWD compared to S as known from
      the literature ("biatrial": S: 181+/-28 ms vs. P: 108+/-13 ms; p<0.05; "dual
      site": S: 120+/-12 ms vs. P: 103+/-17 ms; p<0.05, "septal": S: 132+/-23 ms vs. P:
      84+/-14 ms; p<0.05; and "Bachmann bundle" S: 163+/-14.7 ms vs. P: 134+/-13.5 ms;
      p<0.05). Conclusion This study demonstrates the prolongation of primary normal
      IAA and IEA conduction times by pacing at different locations compared to S.
      Thereby floating pacing using BIMOS results in the smallest prolongation of
      conduction times. Pacing at the Cs-Os does not reduce the IAA conduction time but
      reduces the IEA conduction time in comparison to HRA pacing. On the other hand,
      the new pacing concepts for pace prevention of atrial fibrillation always showed
      a significant reduction of a primary prolonged PWD. This different behavior of
      IAA and IEA conduction times and PWD during pacing has to be taken into account
      before implantation of an atrial pacing lead. 

PMID- 24584433
TI  - [Not Available].
AB  - Recent prospective trials of pacing in atrial fibrillation are inconclusive. A
      substantial suppression of atrial tachyarrhythmias has been observed in patients
      with brady-tachy-syndrome and high rate of paced vs. intrinsic beats. An
      improvement in prognosis, incidence of thromboembolism, rehospitalization and
      improvement in heart failure have been controversally described in different
      trials. The quality of life improves in most studies in physiologic pacing. This
      paper presents a short overview on published and ongoing trials in pacing of
      atrial fibrillation. 

PMID- 24584434
TI  - Cognitive, adaptive, and psychosocial differences between high ability youth with
      and without autism spectrum disorder.
AB  - Research on Autism Spectrum Disorder (ASD) is thriving; however, scant empirical
      research has investigated how ASD manifests in high ability youth. Further
      research is necessary to accurately differentiate high ability students with ASD
      from those without the disorder, and thus decrease the risk of misdiagnosis. The
      purpose of the present study is to provide an empirical account of the
      intellectual, adaptive, and psychosocial functioning of high ability youth with
      and without ASD utilizing a group study design. Forty youth with high cognitive
      ability and ASD and a control group of 41 youth with high cognitive ability and
      no psychological diagnosis were included in the study. In comparison to the
      control group, the ASD group showed poorer functioning on measures of processing
      speed, adaptive skills, and broad psychological functioning, as perceived by
      parents and teachers. These findings have significant implications for diagnosing
      ASD among those with high ability, and the development of related psychological
      and educational interventions to address talent domains and areas of concern. 

PMID- 24584435
TI  - Promoting sexual health equity in the United States: implications from
      exploratory research with African-American adults.
AB  - In an effort to inform communication efforts to promote sexual health equity in
      the United States, the Centers for Disease Control and Prevention sought to
      explore African-Americans' perceptions of the sexually transmitted disease (STD)
      problem in their communities, reactions to racially comparative STD data and
      opinions about dissemination of such information. Semi-structured triads and
      individual interviews were conducted with African-American adults (N = 158) in
      the Southeastern and Midwestern United States. Most participants believed that
      STDs are a problem in their communities but were unaware of the extent to which
      STDs disproportionately affect African Americans. Once informed about racial
      differences in STD rates, participants commonly reacted with shock, fear and
      despair; a minority raised questions about the information's source and
      credibility. Most felt it was critical to get the information out to African
      American communities as a 'wake-up call' to motivate change, though some raised
      concerns about its dissemination. Findings suggest that information about racial
      differences in STD rates must be strategically crafted and delivered through
      targeted channels to be acceptable to African Americans. So as not to further
      harm communities burdened by other social/health inequities, alternative
      (strength-based) approaches should be considered for motivating positive change. 

PMID- 24584438
TI  - Novel synthetic methodology for controlling the orientation of zinc oxide
      nanowires grown on silicon oxide substrates.
AB  - This study presents a simple method to reproducibly obtain well-aligned vertical
      ZnO nanowire arrays on silicon oxide (SiOx) substrates using seed crystals made
      from a mixture of ammonium hydroxide (NH4OH) and zinc acetate (Zn(O2CCH3)2)
      solution. In comparison, high levels of OH(-) concentration obtained using NaOH
      or KOH solutions lead to incorporation of Na or K atoms into the seed crystals,
      destroying the c-axis alignment of the seeds and resulting in the growth of
      misaligned nanowires. The use of NH4OH eliminates the metallic impurities and
      ensures aligned nanowire growth in a wide range of OH(-) concentrations in the
      seed solution. The difference of crystalline orientations between NH4OH- and NaOH
      based seeds is directly observed by lattice-resolved images and electron
      diffraction patterns using a transmission electron microscope (TEM). This study
      obviously suggests that metallic impurities incorporated into the ZnO nanocrystal
      seeds are one of the factors that generates the misaligned ZnO nanowires. This
      method also enables the use of silicon oxide substrates for the growth of
      vertically aligned nanowires, making ZnO nanostructures compatible with widely
      used silicon fabrication technology. 

PMID- 24584437
TI  - Nuclear receptor NR4A1 promotes breast cancer invasion and metastasis by
      activating TGF-beta signalling.
AB  - In advanced cancers, the TGF-beta pathway acts as an oncogenic factor and is
      considered to be a therapeutic target. Here using a genome-wide cDNA screen, we
      identify nuclear receptor NR4A1 as a strong activator of TGF-beta signalling.
      NR4A1 promotes TGF-beta/SMAD signalling by facilitating AXIN2-RNF12/ARKADIA
      induced SMAD7 degradation. NR4A1 interacts with SMAD7 and AXIN2, and potently and
      directly induces AXIN2 expression. Whereas loss of NR4A1 inhibits TGF-beta
      induced epithelial-to-mesenchymal transition and metastasis, slight NR4A1 ectopic
      expression stimulates metastasis in a TGF-beta-dependent manner. Importantly,
      inflammatory cytokines potently induce NR4A1 expression, and potentiate TGF-beta
      mediated breast cancer cell migration, invasion and metastasis in vitro and in
      vivo. Notably, NR4A1 expression is elevated in breast cancer patients with high
      immune infiltration and its expression weakly correlates with phosphorylated
      SMAD2 levels, and is an indicator of poor prognosis. Our results uncover
      inflammation-induced NR4A1 as an important determinant for hyperactivation of pro
      oncogenic TGF-beta signalling in breast cancer. 

PMID- 24584455
TI  - New 5-ylidene rhodanine derivatives based on the dispacamide A model.
AB  - A practical approach for the preparation of (5Z) 5-ylidene rhodanine derivatives
      bearing the (4,5-dihalogeno-pyrrol-2-yl)carbamoyl fragment of dispacamide A is
      reported. The new compounds were obtained in good yields (19-88 %) by Knoevenagel
      condensation according to a solution-phase microwave dielectric heating protocol
      in the presence of organic bases (piperidine, TEA, and AcONa) from a set of N
      substituted rhodanines 2(a-i). The ten synthetic products 3(a-j) have been
      synthesized with a Z-geometry about their exocyclic double bond and the structure
      of one of these compounds (3) was confirmed by a single X-ray diffraction
      analysis. The new (5Z) 5-ylidene rhodanine derivatives 3(a-j) were tested against
      eight protein kinases.

PMID- 24584456
TI  - Impact of pericardium bovine patch (Tutomesh((r))) on incisional hernia treatment
      in contaminated or potentially contaminated fields: retrospective comparative
      study.
AB  - PURPOSE: This retrospective comparative study analyzes the outcome of patients
      affected by incisional hernia in potentially contaminated or contaminated field,
      treated by three operative techniques. METHODS: 152 patients (62 M:90 F; mean age
      65 +/- 14 years) underwent incisional hernia repair (January 2002-January 2012)
      in complicated settings. Criteria of inclusion in the study were represented by
      the following causes of admission: mesh rejection/infection, obstruction without
      gangrene but with possible peritoneal bacterial translocation, obstruction with
      gangrene, enterocutaneous fistula or simultaneous presence of ileo- or colostomy.
      The patients were divided into three groups: A (n = 76), treated with primary
      closure technique; B and C (n = 38 each), with reinforcement by synthetic or
      pericardium bovine mesh (Tutomesh((r))), respectively. The prosthetic groups were
      divided into Onlay and Sublay subgroups. RESULTS: Significant decreases in C vs A
      were observed for wound infection (3 vs 37%) and recurrence (0 vs 14%), and in C
      vs B for wound infection (3 vs 53%), seroma (0 vs 34%) and recurrence (0 vs 16%).
      Patients with concomitant bowel resection (BR) (43%) showed (all P < 0.05) an
      increase of overall morbidity (55 vs 33%) and wound infection rate (42 vs 24%)
      compared to cases without BR. Morbidity presented no significant differences in C
      Onlay or Sublay subgroups. B-Sublay subgroup has (all P < 0.05) lower overall
      morbidity (20 vs 75%), wound infection (10 vs 68%) and seroma (0 vs 46%) than B
      Onlay. CONCLUSIONS: The pericardium bovine patch seems to be safe and effective
      to successfully repair ventral hernia in potentially contaminated operative
      fields, especially in association with bowel resection.

PMID- 24584457
TI  - Theory, analysis, social justice, and criminalizing HIV transmission: a
      commentary on Lehman and colleagues (2014).

PMID- 24584458
TI  - Mental health of HIV-seropositive women during pregnancy and postpartum period: a
      comprehensive literature review.
AB  - With growing numbers of HIV-seropositive (HIV+) women of child-bearing age and
      increased access to effective clinical protocols for preventing mother-to-child
      transmission (MTCT) of HIV, mental health-related factors have become
      increasingly relevant due to their potential to affect the women's quality of
      life, obstetric outcomes and risk of MTCT. This review synthesizes evidence from
      53 peer-reviewed publications examining mental health-related variables in
      pregnant and postpartum HIV+ women. The presentation of results is organized by
      the level of socioeconomic resources in the countries where studies were
      conducted (i.e., high-, middle-, and low-income countries). It is concluded that
      psychiatric symptoms, particularly depression, and mental health vulnerabilities
      (e.g., inadequate coping skills) are widespread among pregnant HIV+ women
      globally and have a potential to affect psychological well-being, quality of life
      and salient clinical outcomes. The current body of evidence provides rationale
      for developing and evaluating clinical and structural interventions aimed at
      improving mental health outcomes and their clinical correlates in pregnant HIV+
      women. 

PMID- 24584459
TI  - A novel bifunctional pectinase from Penicillium oxalicum SX6 with separate pectin
      methylesterase and polygalacturonase catalytic domains.
AB  - A multimodular pectinase of glycoside hydrolase family 28, S6A, was identified in
      Penicillium oxalicum SX6 that consists of an N-terminal catalytic domain of
      pectin methylesterase, a Thr/Ser-rich linker region, and a C-terminal catalytic
      domain of polygalacturonase. Recombinant S6A and its two derivatives, S6PE (the
      catalytic domain of pectin methylesterase) and S6PG (the catalytic domain of
      polygalacturonase), were produced in Pichia pastoris. S6A was a bifunctional
      protein and had both pectin methylesterase and polygalacturonase activities.
      Three enzymes showed similar biochemical properties, such as optimal pH and
      temperature (pH 5.0 and 50  degrees C) and excellent stability at pH 3.5-6.0 and
      40  degrees C. Most metal ions tested (Na(+), K(+), Ca(2+), Li(+), Co(2+),
      Cr(3+), Ni(2+), Cu(2+), Mn(2+),Mg(2+), Fe(3+), Zn(2+), and Pb(2+)) enhanced the
      pectin methylesterase activities of S6PE and S6A, but had little or inhibitory
      effects on the polygalacturonase activities of S6A and S6PG. In comparison with
      most fungal pectin methylesterases, S6A had higher specific activity (271.1 U/mg)
      towards 70 % DM citrus pectin. When S6PE and S6PG were combined at the activity
      ratio of 1:4, the most significant synergistic effect was observed in citrus
      pectin degradation and degumming of sisal fiber, which is comparable with the
      performance of S6A (95 v.s. 100 % and 16.9 v.s. 17.2 %, respectively). To the
      best of our knowledge, this work represents the first report of gene cloning,
      heterologous expression, and biochemical characterization of a bifunctional
      pectinase with separate catalytic domains. 

PMID- 24584460
TI  - Improved n-butanol production by a non-acetone producing Clostridium pasteurianum
      DSMZ 525 in mixed substrate fermentation.
AB  - The kinetics of growth, acid and solvent production in batch culture of
      Clostridium pasteurianum DSMZ 525 were examined in mixed or mono-substrate
      fermentations. In pH-uncontrolled batch cultures, the addition of butyric acid or
      glucose significantly enhanced n-butanol production and the ratio of butanol/1,3
      propanediol. In pH-controlled batch culture at pH = 6, butyric acid addition had
      a negative effect on growth and did not lead to a higher n-butanol productivity.
      On the other hand, mixed substrate fermentation using glucose and glycerol
      enhanced the growth and acid production significantly. Glucose limitation in the
      mixed substrate fermentation led to the reduction or inhibition of the glycerol
      consumption by the growing bacteria. Therefore, for the optimal growth and n
      butanol production by C. pasteurianum, a limitation of either substrate should be
      avoided. Under optimized batch conditions, n-butanol concentration and maximum
      productivity achieved were 21 g/L, and 0.96 g/L * h, respectively. In comparison,
      mixed substrate fermentation using biomass hydrolysate and glycerol gave a n
      butanol concentration of 17 g/L with a maximum productivity of 1.1 g/L * h. In
      terms of productivity and final n-butanol concentration, the results demonstrated
      that C. pasteurianum DSMZ 525 is well suitable for n-butanol production from
      mixed substrates of biomass hydrolysate and glycerol and represents an
      alternative promising production strain. 

PMID- 24584461
TI  - Sensitive quantitative detection of Ralstonia solanacearum in soil by the most
      probable number-polymerase chain reaction (MPN-PCR) method.
AB  - We developed a sensitive quantitative assay for detecting Ralstonia solanacearum
      in soil by most probable number (MPN) analysis based on bio-PCR results. For
      development of the detection method, we optimized an elution buffer containing 5
      g/L skim milk for extracting bacteria from soil and reducing contamination of
      polymerase inhibitors in soil extracts. Because R. solanacearum can grow in water
      without any added nutrients, we used a cultivation buffer in the culture step of
      the bio-PCR that contained only the buffer and antibiotics to suppress the growth
      of other soil microorganisms. To quantify the bacterial population in soil, the
      elution buffer was added to 10 g soil on a dry weight basis so that the combined
      weight of buffer, soil, and soil-water was 50 g; 5 mL of soil extract was assumed
      to originate from 1 g of soil. The soil extract was divided into triplicate
      aliquots each of 5 mL and 500, 50, and 5 MUL. Each aliquot was diluted with the
      cultivation buffer and incubated at 35  degrees C for about 24 h. After
      incubation, 5 MUL of culture was directly used for nested PCR. The number of
      aliquots showing positive results was collectively checked against the MPN table.
      The method could quantify bacterial populations in soil down to 3 cfu/10 g dried
      soil and was successfully applied to several types of soil. We applied the method
      for the quantitative detection of R. solanacearum in horticultural soils, which
      could quantitatively detect small populations (9.3 cfu/g), but the semiselective
      media were not able to detect the bacteria. 

PMID- 24584462
TI  - Analysis of blood flow and local expression of angiogenesis-associated growth
      factors in infected wounds treated with negative pressure wound therapy.
AB  - Angiogenesis is involved in the wound healing process. Increased angiogenesis and
      blood flow constitute a major mechanism of negative pressure wound therapy
      (NPWT), which has been shown to facilitate the healing of infected wounds.
      However, the effect on the expression of angiogensis-related growth factor
      remains unknown. The goal of the current study was to investigate the angiogenic
      factor levels prior to and following NPWT in infected wounds. A total of 20
      patients with infected wounds treated with NPWT were included in the study.
      Patients acted as their own control; the postoperative measurements of patients
      were considered as the experimental group, while preoperative measurements were
      considered as the controlled group. Blood flow was recorded prior to and during
      NPWT. A total of 10 angiogensis-related growth factors were detected using a
      protein biochip array to analyze the change in protein levels prior to NPWT, and
      on the third day during NPWT. All wounds were successfully reconstructed by skin
      grafting or using local flaps following NPWT. NPWT resulted in significantly
      increased blood flow in the wound. There was a significant increase in vascular
      endothelial growth factor (VEGF), EGF, platelet-derived growth factor and
      angiotesin-2 following NPWT, while basic fibroblast growth factor decreased
      significantly. NPWT affects the local expression of angiogenesis-associated
      growth factors, which represents another mechanism to explain how NPWT
      accelerates wound healing. 

PMID- 24584463
TI  - X-ray crystal structure of voltage-gated proton channel.
AB  - The voltage-gated proton channel Hv1 (or VSOP) has a voltage-sensor domain (VSD)
      with dual roles of voltage sensing and proton permeation. Its gating is sensitive
      to pH and Zn(2+). Here we present a crystal structure of mouse Hv1 in the resting
      state at 3.45-A resolution. The structure showed a 'closed umbrella' shape with a
      long helix consisting of the cytoplasmic coiled coil and the voltage-sensing
      helix, S4, and featured a wide inner-accessible vestibule. Two out of three
      arginines in S4 were located below the phenylalanine constituting the gating
      charge-transfer center. The extracellular region of each protomer coordinated a
      Zn(2+), thus suggesting that Zn(2+) stabilizes the resting state of Hv1 by
      competing for acidic residues that otherwise form salt bridges with voltage
      sensing positive charges on S4. These findings provide a platform for
      understanding the general principles of voltage sensing and proton permeation. 

PMID- 24584464
TI  - Mechanism of IRSp53 inhibition and combinatorial activation by Cdc42 and
      downstream effectors.
AB  - The Rho family GTPase effector IRSp53 has essential roles in filopodia formation
      and neuronal development, but its regulatory mechanism is poorly understood.
      IRSp53 contains a membrane-binding BAR domain followed by an unconventional CRIB
      motif that overlaps with a proline-rich region (CRIB-PR) and an SH3 domain that
      recruits actin cytoskeleton effectors. Using a fluorescence reporter assay, we
      show that human IRSp53 adopts a closed inactive conformation that opens
      synergistically with the binding of human Cdc42 to the CRIB-PR and effector
      proteins, such as the tumor-promoting factor Eps8, to the SH3 domain. The crystal
      structure of Cdc42 bound to the CRIB-PR reveals a new mode of effector binding to
      Rho family GTPases. Structure-inspired mutations disrupt autoinhibition and Cdc42
      binding in vitro and decouple Cdc42- and IRSp53-dependent filopodia formation in
      cells. The data support a combinatorial mechanism of IRSp53 activation. 

PMID- 24584465
TI  - Depressive Symptoms and Longitudinal Changes in Cognition: Women's Health
      Initiative Study of Cognitive Aging.
AB  - Elevated depressive symptoms (DS) are associated with incident mild cognitive
      impairment and probable dementia in postmenopausal women. We examined the
      association of elevated DS with domain-specific cognitive changes and the
      moderating role of cardiovascular risk factor severity and cardiovascular disease
      (CVD). A total of 2221 elderly women who participated in the Women's Health
      Initiative Study of Cognitive Aging were separated into those with (N = 204) and
      without (N = 2017) elevated DS. The DS and multidomain cognitive outcomes were
      measured annually for an average follow-up of 5.04 years. Women with elevated DS
      showed baseline multidomain cognitive deficits but longitudinal declines in
      global cognition only. Persistent DS was related to greater global cognition,
      verbal knowledge and fluency, and memory declines. Significant DS-CVD
      interactions were observed cross-sectionally (but not longitudinally) for figural
      memory and fine motor speed. Future studies should investigate the role of
      nonvascular mechanisms linking DS and cognitive decline. 

PMID- 24584466
TI  - Polymorphism in Cytochrome P450 2D6, Glutathione S-Transferases Pi 1 Genes, and
      Organochlorine Pesticides in Alzheimer Disease: A Case-Control Study in North
      Indian Population.
AB  - OBJECTIVES: It has been assumed that the association between Alzheimer disease
      (AD) and pesticides may be stronger among genetically susceptible individuals.
      The aim of the study was to examine the genetic polymorphism in cytochrome P450
      2D6 (CYP2D6) and glutathione S-transferases pi 1 (GSTP1) with respect to
      organochlorine pesticides (OCPs) and metals in AD. METHODS: This study included
      100 patients with AD and 100 age-matched controls. The genetic polymorphisms were
      analyzed by restriction fragment length polymorphism. The OCPs and serum metal
      levels were determined using gas chromatography and an autoanalyzer,
      respectively. RESULTS: We found a statistically significant association between
      AD and high levels of beta-hexachlorocyclohexane (beta-HCH; odds ratio [OR] =
      2.064, 95% confidence intervals [95% CIs] = 1.373-3.102, dieldrin [OR = 2.086,
      95% CI = 1.224-3.555], and copper [OR = 1.038, 95% CI = 1.012-1.064). The
      significant low level of magnesium (OR = 0.151, 95% CI = 0.047-0.489) even
      appears to have a protective role against AD. The GSTP1*B (P = .009) and GSTP1*C
      (P = .011) allelic variants were associated with increase in AD risk. CONCLUSION:
      This study demonstrates that the GSTP1*B and *C allelic variants may be
      considered a candidate gene for AD. It can be suggested that although CYP2D6*4
      polymorphism is not a risk of AD, the CYP2D6*4 and GSTP1 polymorphism may
      interact with beta-HCH, dieldrin, and copper to influence the risk of AD.

PMID- 24584474
TI  - Novel antibody binding determinants on the capsid surface of serotype O foot-and
      mouth disease virus.
AB  - Five neutralizing antigenic sites have been described for serotype O foot-and
      mouth disease viruses (FMDV) based on monoclonal antibody (mAb) escape mutant
      studies. However, a mutant virus selected to escape neutralization of mAb binding
      at all five sites was previously shown to confer complete cross-protection with
      the parental virus in guinea pig challenge studies, suggesting that amino acid
      residues outside the mAb binding sites contribute to antibody-mediated in vivo
      neutralization of FMDV. Comparison of the ability of bovine antisera to
      neutralize a panel of serotype O FMDV identified three novel putative sites at
      VP2-74, VP2-191 and VP3-85, where amino acid substitutions correlated with
      changes in sero-reactivity. The impact of these positions was tested using site
      directed mutagenesis to effect substitutions at critical amino acid residues
      within an infectious copy of FMDV O1 Kaufbeuren (O1K). Recovered viruses
      containing additional mutations at VP2-74 and VP2-191 exhibited greater
      resistance to neutralization with both O1K guinea pig and O BFS bovine antisera
      than a virus that was engineered to include only mutations at the five known
      antigenic sites. The changes at VP2-74 and VP3-85 are adjacent to critical amino
      acids that define antigenic sites 2 and 4, respectively. However VP2-191 (17 A
      away from VP2-72), located at the threefold axis and more distant from previously
      identified antigenic sites, exhibited the most profound effect. These findings
      extend our knowledge of the surface features of the FMDV capsid known to elicit
      neutralizing antibodies, and will improve our strategies for vaccine strain
      selection and rational vaccine design. 

PMID- 24584475
TI  - Viral determinants of influenza A virus host range.
AB  - Typical avian influenza A viruses are restricted from replicating efficiently and
      causing disease in humans. However, an avian virus can become adapted to humans
      by mutating or recombining with currently circulating human viruses. These
      viruses have the potential to cause pandemics in an immunologically naive human
      population. It is critical that we understand the molecular basis of host-range
      restriction and how this can be overcome. Here, we review our current
      understanding of the mechanisms by which influenza viruses adapt to replicate
      efficiently in a new host. We predominantly focus on the influenza polymerase,
      which remains one of the least understood host-range barriers.

PMID- 24584476
TI  - Genome sequencing identifies genetic and antigenic divergence of porcine
      picobirnaviruses.
AB  - The full-length genome sequence of a porcine picobirnavirus (PBV) detected in
      Italy in 2004 was determined. The smaller (S) genome segment was 1730 nt, coding
      for a putative RNA-dependent RNA polymerase. Two distinct subpopulations of
      larger (L) genome segment (LA and LB) were identified in the sample, with the
      sizes ranging from 2351 to 2666 nt. The ORF1, coding for a protein of unknown
      function, contained a variable number of repetitions of the ExxRxNxxxE motif. The
      capsid protein-coding ORF2 spanned nt 810-2447 in the LB variants and started at
      nt 734 in the LA variants. However, a termination codon was present only in one
      of all the LA segment variants. Three-dimensional modelling of the porcine PBV
      capsids suggested structural differences in the protruding domain, tentatively
      involved as antigens in the humoral immune response. Altogether, these findings
      suggest the simultaneous presence of two different PBV strains sharing the same S
      segment but displaying genetically diverse L segments. In addition, the sample
      probably contained a mixture of PBVs with aberrant RNA replication products.
      Altered structure in the L segments could be tolerated and retained in the
      presence of functionally integer-cognate genes and represents a mechanism of
      virus diversification. 

PMID- 24584479
TI  - HPV-related cervical disease and oropharyngeal cancer.
AB  - Human papillomavirus (HPV), especially HPV 16, is associated with the development
      of both cervical and oral cancer. We show the case of a woman affected by HPV
      related cervical disease and oropharyngeal squamous cell carcinoma (OPSCC). A 41
      year-old woman arrived at our Colposcopy Center following an abnormal Pap smear
      result (ASC-H) and a diagnosis of moderate cervical dysplasia obtained by a
      cervical biopsy. She underwent a colposcopy that showed a cervical abnormal
      transformation zone grade 2. A laser conization was performed in November 2010.
      Histology reported a moderate/severe dysplasia. The cone resection margins were
      free. Follow-up colposcopy and cytology were negative. The HPV testing showed an
      infection by HPV 16. In October 2012, the patient presented to the Head-Neck ER
      after episodes of hemoptysis; a lesion was found in the left tonsillar lodge. A
      biopsy was performed with a result of squamous cell carcinoma with low-grade
      differentiation. The HPV testing detected a high-risk HPV and the
      immunohistochemical analysis was positive for p16. She was treated by
      chemotherapy and brachytherapy. She was followed at the head-neck center with
      monthly visits with oral visual inspection that showed complete absence of
      mucosal abnormalities. HPV-related OPSCC and cervical precancerous/cancerous
      lesions have significant similarities in terms of pathogenesis. They are both
      caused largely by HPV 16, as in the present case. In conclusion, because of this
      association found in literature and in our case, we think that women with HPV
      cervical lesions should have regular surveillance for oropharyngeal cancer,
      whereas women with OPSCC should be encouraged to have diligent cervical
      screening.

PMID- 24584478
TI  - Activation pathway of Src kinase reveals intermediate states as targets for drug
      design.
AB  - Unregulated activation of Src kinases leads to aberrant signalling, uncontrolled
      growth and differentiation of cancerous cells. Reaching a complete mechanistic
      understanding of large-scale conformational transformations underlying the
      activation of kinases could greatly help in the development of therapeutic drugs
      for the treatment of these pathologies. In principle, the nature of
      conformational transition could be modelled in silico via atomistic molecular
      dynamics simulations, although this is very challenging because of the long
      activation timescales. Here we employ a computational paradigm that couples
      transition pathway techniques and Markov state model-based massively distributed
      simulations for mapping the conformational landscape of c-src tyrosine kinase.
      The computations provide the thermodynamics and kinetics of kinase activation for
      the first time, and help identify key structural intermediates. Furthermore, the
      presence of a novel allosteric site in an intermediate state of c-src that could
      be potentially used for drug design is predicted. 

PMID- 24584480
TI  - Molecules in the mirror: how SERS backgrounds arise from the quantum method of
      images.
AB  - The Raman coupling of light to molecular vibrations is strongly modified when
      they are placed near a plasmonic metal surface, with the appearance of a strong
      broad continuum background in addition to the normal surface-enhanced Raman
      scattering (SERS) peaks. Using a quantum method of images approach, we produce a
      simple but quantitative explanation of the inevitable presence of the background,
      due to the resistive damping of the image molecule. This model thus suggests new
      strategies for enhancing the SERS peak to background ratio. 

PMID- 24584481
TI  - Spin-induced band modifications of graphene through intercalation of magnetic
      iron atoms.
AB  - Intercalation of magnetic iron atoms through graphene formed on the SiC(0001)
      surface is found to induce significant changes in the electronic properties of
      graphene due mainly to the Fe-induced asymmetries in charge as well as spin
      distribution. From our synchrotron-based photoelectron spectroscopy data together
      with ab initio calculations, we observe that the Fe-induced charge asymmetry
      results in the formation of a quasi-free-standing bilayer graphene while the spin
      asymmetry drives multiple spin-split bands. We find that Fe adatoms are best
      intercalated upon annealing at 600  degrees C, exhibiting split linear pi-bands,
      characteristic of a bilayer graphene, but much diffused. Subsequent changes in
      the C 1s, Si 2p, and Fe 3p core levels are consistently described in terms of Fe
      intercalation. Our calculations together with a spin-dependent tight binding
      model ascribe the diffuse nature of the pi-bands to the multiple spin-split bands
      originated from the spin-injected carbon atoms residing only in the lower
      graphene layer. 

PMID- 24584482
TI  - Computational atomistic blueprinting of novel conducting copolymers using
      particle swarm optimization.
AB  - A proficient metaheuristic approach viz., particle swarm optimization coupled
      with negative factor counting technique and inverse iteration method has been
      employed for designing novel binary and ternary copolymers based on thiophene,
      pyrrole and furan skeletons. A comparative study of the electronic structures and
      conduction properties of neutral heterocyclic copolymers and their benzene
      substituted analogues is inferred using the band structure results derived from
      ab-initio Hartree-Fock crystal orbital calculations. The band gap value decreases
      as a result of substitution on the polymer backbone due to increased quinoid
      contributions which is expected to enhance the intrinsic conductivity of the
      resulting copolymers. In general, it has been found that HOMO energies have a
      more decisive influence than LUMO energies on the relative fraction of
      constituents of the respective low band gap copolymers. The trends in the
      electronic properties of the respective copolymers are also verified and
      discussed with the help of density of states. These results can help streamline
      scrupulous synthetic efforts providing a potent route for molecular engineering
      of sustainable and efficient electronic materials. 

PMID- 24584483
TI  - Role of adenosine A2B receptor signaling in contribution of cardiac mesenchymal
      stem-like cells to myocardial scar formation.
AB  - Adenosine levels increase in ischemic hearts and contribute to the modulation of
      that pathological environment. We previously showed that A2B adenosine receptors
      on mouse cardiac Sca1(+)CD31(-) mesenchymal stromal cells upregulate secretion of
      paracrine factors that may contribute to the improvement in cardiac recovery seen
      when these cells are transplanted in infarcted hearts. In this study, we tested
      the hypothesis that A2B receptor signaling regulates the transition of
      Sca1(+)CD31(-) cells, which occurs after myocardial injury, into a myofibroblast
      phenotype that promotes myocardial repair and remodeling. In vitro, TGFbeta1
      induced the expression of the myofibroblast marker alpha-smooth muscle actin
      (alphaSMA) and increased collagen I generation in Sca1(+)CD31(-) cells.
      Stimulation of A2B receptors attenuated TGFbeta1-induced collagen I secretion but
      had no effect on alphaSMA expression. In vivo, myocardial infarction resulted in
      a rapid increase in the numbers of alphaSMA-positive cardiac stromal cells by day
      5 followed by a gradual decline. Genetic deletion of A2B receptors had no effect
      on the initial accumulation of alphaSMA-expressing stromal cells but hastened
      their subsequent decline; the numbers of alphaSMA-positive cells including
      Sca1(+)CD31(-) cells remained significantly higher in wild type compared with A2B
      knockout hearts. Thus, our study revealed a significant contribution of cardiac
      Sca1(+)CD31(-) cells to the accumulation of alphaSMA-expressing cells after
      infarction and implicated A2B receptor signaling in regulation of myocardial
      repair and remodeling by delaying deactivation of these cells. It is plausible
      that this phenomenon may contribute to the beneficial effects of transplantation
      of these cells to the injured heart. 

PMID- 24584484
TI  - Rectal carcinoids: a systematic review.
AB  - BACKGROUND: Rectal carcinoids are increasing in incidence worldwide. Frequently
      thought of as a relatively benign condition, there are limited data regarding
      optimal treatment strategies for both localized and more advanced disease. The
      aim of this study was to summarize published experiences with rectal carcinoids
      and to present the most current data. METHODS: Following PRISMA guidelines, an
      electronic literature search performed of PubMed, Medline, Embase, and the
      Cochrane Library using the terms "rectum" or "rectal" AND "carcinoid" over a 20
      year study period from January 1993 to May 2013. Non-English-language studies,
      animal studies, and studies of fewer than 100 patients were excluded. Study end
      points included demographic information, tumor features, intervention and
      outcomes. All included articles were quality assessed. RESULTS: Using the search
      parameters and exclusions as outlined above, a total of 14 articles were
      identified for detailed analysis. The quality of articles was low/moderate for
      all included scoring 9 to 17 of 27. The articles included 4,575 patients
      diagnosed with a rectal carcinoid. Approximately 80% of tumors were <10 mm, 15%
      11-20 mm, and 5% >20 mm. Eight percent of patients presented with regional lymph
      node metastases, and 4% presented with distant metastases. Tumor size >10 mm, and
      muscular and lymphovascular invasion are independently associated with an
      increased risk of metastases. The 5-year survival was 93% in patients presenting
      with localized disease and 86% overall. CONCLUSIONS: Small tumors up to 10 mm
      without any adverse features can be treated with endoscopic or local excision.
      The treatment of carcinoids between 10 and 20 mm is still contentious, but those
      up to 16 mm without adverse feature are suitable for local/endoscopic excision
      followed by careful histopathological assessment. Those >20 mm or with adverse
      features require radical surgery with mesorectal clearance in suitable patients.

PMID- 24584485
TI  - Perceived injustice in fibromyalgia and rheumatoid arthritis.
AB  - This is a pilot study to compare levels of perceived injustice via the Injustice
      Experience Questionnaire in patients with fibromyalgia or rheumatoid arthritis.
      Two cohorts of patients, one with fibromyalgia (FM), one with rheumatoid
      arthritis (RA), completed the Injustice Experience Questionnaire, a visual
      analogue pain scale, and the Hospital Anxiety and Depression Scale (HADS).
      Inferential statistics were then used to determine whether participants in the
      two diagnostic groups had significantly different scores on the Perceived
      Injustice Questionnaire. This was done univariately using t tests and after
      adjusting for potential confounders using ANCOVA. We also examined crude
      associations between the variables using Pearson correlation coefficients, then
      examined the adjusted association between diagnostic group and perceived
      injustice using multivariable linear regression. Our final models were built in a
      blocked fashion by initially entering diagnostic category into the model, then
      entering other variables simultaneously using a stepwise strategy (p-to-enter
      <=.05, p-to-remove >=.10). A total of 126 participants (64 FM, 62 RA) completed
      all questionnaires. The FM group had a greater percentage of female participants,
      more severe pain, more severe anxiety and more severe depression. In unadjusted
      analysis, the FM group had higher Injustice Experience Questionnaire scores. When
      the RA and FM group scores for the Injustice Experience Questionnaire are
      adjusted for pain levels, there is no statistically significant difference
      between groups. Adjustment for HADS anxiety and HADS depression does not
      significantly affect the Injustice Experience Questionnaire scores after
      adjustment for pain. Fibromyalgia is associated with a higher level of perceived
      injustice than is seen with rheumatoid arthritis. This difference appears to be
      associated with higher levels of pain reported by fibromyalgia patients, and
      therefore may not be specific to the diagnosis. Prospective studies may help to
      resolve this issue. 

PMID- 24584486
TI  - Acute septic arthritis of the acromioclavicular joint caused by Haemophilus
      parainfluenzae: a rare causative origin.
AB  - Septic arthritis of the acromioclavicular (AC) joint is a rare entity with
      symptoms that include erythema, swelling, and tenderness over the AC joint,
      fever, and limitation of shoulder motion with pain. In previous reports,
      Staphylococcus and Streptococcus species have been mentioned as common causative
      organisms. Haemophilus parainfluenzae is a normal inhabitant of the oral cavity,
      respiratory tract, gastrointestinal tract, and urogenital tract. However, it
      sometimes causes opportunistic infections leading to septic arthritis and
      osteomyelitis. AC joint infection associated with H.parainfluenzae is very rare,
      and only one case has been reported in the literature. Moreover, septic arthritis
      in immunocompetent patients is also very rare. Here, we report the case of a
      healthy patient with H. parainfluenzae-related septic arthritis of the AC joint.

PMID- 24584499
TI  - The Haemophilus cryptic genospecies Cha adhesin has at least two variants that
      differ in host cell binding, bacterial aggregation, and biofilm formation
      properties.
AB  - The Haemophilus cryptic genospecies (HCG) causes genital tract infections in
      pregnant and postpartum women and respiratory infections in neonates. The major
      surface adhesin in HCG is called Cha, which mediates bacterial adherence to
      cultured human epithelial cells. In this study, we report that there are two
      antigenically distinct variants of Cha, dubbed Cha1 and Cha2. These variants are
      encoded by the same genetic locus in diverse strains and have nearly identical N
      terminal export and C-terminal surface anchoring domains but significantly
      different internal adhesive domains. Based on the comparison of derivatives of a
      laboratory strain of Haemophilus influenzae expressing either surface-associated
      Cha1 or surface-associated Cha2, Cha1 mediates a higher level of adherence to
      cultured human epithelial cells and Cha2 mediates a higher level of adherence to
      abiotic surfaces. We hypothesize that variation in the Cha1 and Cha2 internal
      region results in changes in binding specificity or binding affinity and may be
      associated with adaptation to different host environments during colonization and
      disease. 

PMID- 24584498
TI  - Purification and characterization of phosphonoglycans from Glycomyces sp. strain
      NRRL B-16210 and Stackebrandtia nassauensis NRRL B-16338.
AB  - Two related actinomycetes, Glycomyces sp. strain NRRL B-16210 and Stackebrandtia
      nassauensis NRRL B-16338, were identified as potential phosphonic acid producers
      by screening for the gene encoding phosphoenolpyruvate (PEP) mutase, which is
      required for the biosynthesis of most phosphonates. Using a variety of analytical
      techniques, both strains were subsequently shown to produce phosphonate
      containing exopolysaccharides (EPS), also known as phosphonoglycans. The
      phosphonoglycans were purified by sequential organic solvent extractions,
      methanol precipitation, and ultrafiltration. The EPS from the Glycomyces strain
      has a mass of 40 to 50 kDa and is composed of galactose, xylose, and five
      distinct partially O-methylated galactose residues. Per-deutero-methylation
      analysis indicated that galactosyl residues in the polysaccharide backbone are
      3,4-linked Gal, 2,4-linked 3-MeGal, 2,3-linked Gal, 3,6-linked 2-MeGal, and 4,6
      linked 2,3-diMeGal. The EPS from the Stackebrandtia strain is comprised of
      glucose, galactose, xylose, and four partially O-methylated galactose residues.
      Isotopic labeling indicated that the O-methyl groups in the Stackebrandtia
      phosphonoglycan arise from S-adenosylmethionine. The phosphonate moiety in both
      phosphonoglycans was shown to be 2-hydroxyethylphosphonate (2-HEP) by (31)P
      nuclear magnetic resonance (NMR) and mass spectrometry following strong acid
      hydrolysis of the purified molecules. Partial acid hydrolysis of the purified EPS
      from Glycomyces yielded 2-HEP in ester linkage to the O-5 or O-6 position of a
      hexose and a 2-HEP mono(2,3-dihydroxypropyl)ester. Partial acid hydrolysis of
      Stackebrandtia EPS also revealed the presence of 2-HEP mono(2,3
      dihydroxypropyl)ester. Examination of the genome sequences of the two strains
      revealed similar pepM-containing gene clusters that are likely to be required for
      phosphonoglycan synthesis. 

PMID- 24584500
TI  - Mycobacterium tuberculosis Latin American-Mediterranean family and its
      sublineages in the light of robust evolutionary markers.
AB  - Mycobacterium tuberculosis has a clonal population structure, and the Latin
      American-Mediterranean (LAM) family is one of the largest and most widespread
      within this species, showing evidence for remarkable pathobiology and a confusing
      phylogeny. Here, we applied robust phylogenetic markers to study the evolution of
      the LAM family and its major sublineages circulating in Russia and neighboring
      countries. A total of 250 M. tuberculosis isolates were confirmed to belong to
      the LAM family based on the analysis of the LAM-specific single-nucleotide
      polymorphisms (SNPs) in the Rv3062 and Rv0129c genes. At this stage, the family
      status was rectified for 121 isolates misleadingly assigned by CRISPR
      spoligotyping to non-LAM families (T1- or T5-RUS1). Consequently, the reestimated
      LAM prevalence rate increased 2-fold in Russia and Kazakhstan and 4-fold in
      Belarus. The majority (91.8 to 98.7%) of the LAM isolates from all three
      countries belonged to the LAM-RUS sublineage. In contrast, the Ibero-American LAM
      RD-Rio sublineage was identified in only 7 Russian isolates. Taken together, our
      findings and further analyses suggest a monophyletic origin of LAM-RUS: at a
      historically distant time, in Russia, in a small founding bacterial/human
      population. Its dissemination pattern and high prevalence rate in Northern
      Eurasia may indicate a long-term coexistence of the LAM-RUS sublineage and local
      human populations hypothetically leading to coadaptation and reduced
      pathogenicity of the relatively more ancient clones, such as spoligotype
      international type 254 (SIT254), compared to the more recent SIT252 and SIT266
      clones. In contrast, rare LAM RD-Rio isolates were likely brought to Russia
      through occasional human contact. The spread of RD-Rio strains is not as global
      as commonly claimed and is determined largely by human migration flows (rather
      than by pathobiological properties of these strains). Consequently, a host
      population factor appears to play a major role in shaping the in situ
      dissemination pattern of the imported strains in an autochthonous population. 

PMID- 24584511
TI  - Heme bound amylin self-assembled monolayers on an Au electrode: an efficient bio
      electrode for O2 reduction to H2O.
AB  - Self-assembled monolayers of the water soluble hydrophilic part of naturally
      occurring amylin and its Arg11 mutant have been assembled on an Au surface, which
      are found to efficiently catalyze selective 4e(-)/4H(+) O2 reduction reaction
      (ORR) upon binding heme with a kcat of ~10(7) M(-1) s(-1) under ambient
      conditions, where the Arg11 residue plays the key role of proton transfer in
      determining the rate of ORR. 

PMID- 24584501
TI  - Structure of bacterial transcription factor SpoIIID and evidence for a novel mode
      of DNA binding.
AB  - SpoIIID is evolutionarily conserved in endospore-forming bacteria, and it
      activates or represses many genes during sporulation of Bacillus subtilis. An
      SpoIIID monomer binds DNA with high affinity and moderate sequence specificity.
      In addition to a predicted helix-turn-helix motif, SpoIIID has a C-terminal basic
      region that contributes to DNA binding. The nuclear magnetic resonance (NMR)
      solution structure of SpoIIID in complex with DNA revealed that SpoIIID does
      indeed have a helix-turn-helix domain and that it has a novel C-terminal helical
      extension. Residues in both of these regions interact with DNA, based on the NMR
      data and on the effects on DNA binding in vitro of SpoIIID with single-alanine
      substitutions. These data, as well as sequence conservation in SpoIIID binding
      sites, were used for information-driven docking to model the SpoIIID-DNA complex.
      The modeling resulted in a single cluster of models in which the recognition
      helix of the helix-turn-helix domain interacts with the major groove of DNA, as
      expected. Interestingly, the C-terminal extension, which includes two helices
      connected by a kink, interacts with the adjacent minor groove of DNA in the
      models. This predicted novel mode of binding is proposed to explain how a monomer
      of SpoIIID achieves high-affinity DNA binding. Since SpoIIID is conserved only in
      endospore-forming bacteria, which include important pathogenic Bacilli and
      Clostridia, whose ability to sporulate contributes to their environmental
      persistence, the interaction of the C-terminal extension of SpoIIID with DNA is a
      potential target for development of sporulation inhibitors. 

PMID- 24584512
TI  - Flow cytometric viability assessment of lactic acid bacteria starter cultures
      produced by fluidized bed drying.
AB  - For starter culture production, fluidized bed drying is an efficient and cost
      effective alternative to the most frequently used freeze drying method. However,
      fluidized bed drying also poses damaging or lethal stress to bacteria. Therefore,
      investigation of impact of process variables and conditions on viability of
      starter cultures produced by fluidized bed drying is of major interest. Viability
      of bacteria is most frequently assessed by plate counting. While reproductive
      growth of cells can be characterized by the number of colony-forming units, it
      cannot provide the number of viable-but-nonculturable cells. However, in starter
      cultures, these cells still contribute to the fermentation during food
      production. In this study, flow cytometry was applied to assess viability of
      Lactobacillus plantarum starter cultures by membrane integrity analysis using
      SYBR(r)Green I and propidium iodide staining. The enumeration method established
      allowed for rapid, precise and sensitive determination of viable cell
      concentration, and was used to investigate effects of fluidized bed drying and
      storage on viability of L. plantarum. Drying caused substantial membrane damage
      on cells, most likely due to dehydration and oxidative stress. Nevertheless, high
      bacterial survival rates were obtained, and granulates contained in the average
      2.7 * 10(9) viable cells/g. Furthermore, increased temperatures reduced viability
      of bacteria during storage. Differences in results of flow cytometry and plate
      counting suggested an occurrence of viable-but-nonculturable cells during
      storage. Overall, flow cytometric viability assessment is highly feasible for
      rapid routine in-process control in production of L. plantarum starter cultures,
      produced by fluidized bed drying. 

PMID- 24584513
TI  - Genetic engineering of the green alga Chlorella zofingiensis: a modified
      norflurazon-resistant phytoene desaturase gene as a dominant selectable marker.
AB  - The unicellular green alga Chlorella zofingiensis has been proposed as a
      promising producer of natural astaxanthin, a commercially important
      ketocarotenoid. But the genetic toolbox for this alga is not available. In the
      present study, an efficient transformation system was established for C.
      zofingiensis. The transformation system utilized a modified norflurazon-resistant
      phytoene desaturase (PDS-L516F, with an leucine-phenylalanine change at position
      516) as the selectable marker. Three promoters from endogenous PDS, nitrate
      reductase (NIT), and ribulose-1,5-bisphosphate carboxylase/oxygenase small
      subunit (RBCS) genes were tested, with the RBCS promoter demonstrating the
      highest transformation efficiency. Inclusion of the first intron of the PDS gene
      further enhanced the efficiency by 91 %. Both particle bombardment and
      electroporation methods were examined, and the latter gave a fourfold higher
      transformation efficiency. The introduction of PDS-L516F, which exhibited a 33 %
      higher desaturation activity than the unaltered enzyme, enabled C. zofingiensis
      to produce 32.1 % more total carotenoids (TCs) and 54.1 % more astaxanthin. The
      enhanced accumulation of astaxanthin in transformants was revealed to be related
      to the increase in the transcripts of PDS, beta-carotenoid ketolase (BKT), and
      hydroxylase (CHYb) genes. Our study clearly shows that the modified PDS gene is a
      dominant selectable marker for the transformation of C. zofingiensis and possibly
      for the genetic engineering of the carotenoid biosynthetic pathway. In addition,
      the engineered C. zofingiensis might serve as an improved source of natural
      astaxanthin. 

PMID- 24584514
TI  - Is aceticlastic methanogen composition in full-scale anaerobic processes related
      to acetate utilization capacity?
AB  - In this study, biomass samples were obtained from six municipal and nine
      industrial full-scale anaerobic processes to investigate whether the aceticlastic
      methanogen population composition is related to acetate utilization capacity and
      the nature of the wastewater treated, i.e. municipal sludge or industrial
      wastewater. Batch serum bottle tests were used to determine the specific acetate
      utilization rate (AUR), and a quantitative real-time polymerase chain reaction
      protocol was used to enumerate the acetate-utilizing Methanosaeta and
      Methanosarcina populations in the biomass samples. Methanosaeta was the dominant
      aceticlastic methanogen in all samples, except for one industrial wastewater
      treating anaerobic process. However, Methanosarcina density in industrial biomass
      samples was higher than the Methanosarcina density in the municipal samples. The
      average AUR values of municipal and industrial wastewater treatment plant biomass
      samples were 10.49 and 10.65 mg CH3COO(-)/log(aceticlastic methanogen gene
      copy).d, respectively. One-way ANOVA test and principle component analysis showed
      that the acetate utilization capacities and aceticlastic methanogen community
      composition did not show statistically significant correlation among the
      municipal digesters and industrial wastewater-treating processes investigated. 

PMID- 24584515
TI  - The role of Aspergillus flavus veA in the production of extracellular proteins
      during growth on starch substrates.
AB  - The aflatoxin-producer and opportunistic plant pathogenic, filamentous fungus
      Aspergillus flavus is responsible for the contamination of corn and other
      important agricultural commodities. In order to obtain nutrients from the host A.
      flavus produces a variety of extracellular hydrolytic enzymes. Interestingly, A.
      flavus amylase and protease activity are dependent on the global regulator veA, a
      gene known to regulate morphogenesis and secondary metabolism in numerous fungi.
      Analysis of starch degradation by fungal enzymes secreted into broths of starch-
      or corn kernel-based media showed a notable accumulation of glucose in samples of
      the A. flavus control strain while the deletion veA sample accumulated high
      levels of maltose and maltotriose and only a small amount of glucose.
      Furthermore, SDS-PAGE and proteomics analysis of culture broths from starch- or
      corn kernel-based media demonstrated differential production of a number of
      proteins that included a reduction in the amount of a glucoamylase protein in the
      veA mutant compared to the control strain, while an alpha-amylase was produced in
      greater quantities in the veA mutant. Quantitative real-time PCR and western blot
      analyses using anti-glucoamylase or alpha-amylase antisera supported the
      proteomics results. Additionally, an overall reduction in protease activity was
      observed in the veA mutant including production of the alkaline protease, oryzin,
      compared to the control strain. These findings contribute to our knowledge of
      mechanisms controlling production of hydrolases and other extracellular proteins
      during growth of A. flavus on natural starch-based substrates. 

PMID- 24584516
TI  - VaCPK20 gene overexpression significantly increased resveratrol content and
      expression of stilbene synthase genes in cell cultures of Vitis amurensis Rupr.
AB  - Resveratrol, a naturally occurring plant phenol, has been reported to exhibit a
      wide range of valuable biological and pharmacological properties. In the present
      investigation, we show that transformation of a Vitis amurensis Rupr. cell
      suspension with the gene VaCPK20 for a calcium-dependent protein kinase (CDPK)
      under the control of double CaMV 35S promoter increased resveratrol production in
      five independently transformed cell lines in 9-68 times compared with control
      cells. The VaCPK20-transformed calli were capable of producing 0.04-0.42 % dry
      wt. of resveratrol, while the control calli produced up to 0.008 % dry wt. of
      resveratrol Also, we characterized expression of stilbene synthase (STS) genes in
      the five VaCPK20-transgenic cell lines of V. amurensis. In all VaCPK20-transgenic
      cell lines, expression of VaSTS7 increased; while expression of VaSTS1 decreased.
      We suggest that transformation of V. amurensis calli with the VaCPK20 gene
      induced resveratrol accumulation via enhancement of expression of the VaSTS7 gene
      involved in resveratrol biosynthesis. The obtained data first demonstrate that
      overexpression of a CDPK gene resulted in increased accumulation of a stilbenoid
      phytoalexine in transgenic plant cells. We propose that the VaCPK20 gene could
      play an important role in the regulation of resveratrol biosynthesis in grape
      cells.

PMID- 24584517
TI  - Mitochondrial DNA phylogeography of Semisulcospira libertina (Gastropoda:
      Cerithioidea: Pleuroceridae): implications the history of landform changes in
      Taiwan.
AB  - The mitochondrial DNA cytochrome c oxidase subunit I sequences from 95 specimens
      of Semisulcospira libertina in Taiwan were identified as two major phylogroups,
      exhibiting a southern and northern distribution, north of Formosa Bank and south
      of Miaoli Plateau. The genetic distance between these two phylogroups was 12.20%,
      and the distances within-phylogroups were 4.97 and 5.56%. According to a
      molecular clock of 1.56% per lineage per million years, the divergence time
      between these two major phylogroups was estimated at 4.94 million years ago
      (mya), with the two phylogroups forming at 3.64 and 3.75 mya, respectively.
      Moreover, the geological events have suggested that Taiwan Island emerged above
      sea level at 4-5 mya, and became its present shape at 2 mya. These results
      suggested that these two phylogroups might originate from two independent
      ancestral populations or divergent before colonizing Taiwan. Within South
      phylogroup, the initial colonization was hypothesized to be in Kaoping River
      (WT), followed by its northward. The high divergence between south- and north of
      WT River was influenced by the formation of the Kaoping foreland basins. Within
      North phylogroup, the colonization was from central sub-region through paleo
      Miaoli Plateau to northern and northeastern sub-regions. This study showed that
      the landform changes might have shaped the genetic structure of S. libertina in
      concert. Apparently, two cryptic species or five different genetic stocks of S.
      libertina could be identified; these results are useful for the evaluation and
      conservation of S. libertina in Taiwan.

PMID- 24584518
TI  - The role of genetic risk factors in arterial ischemic stroke in pediatric and
      adult patients: a critical review.
AB  - The incidence of arterial ischemic stroke (AIS) in childhood (about 2-13 per
      100,000 children a year) is much lower than the incidence in the adult
      population. Still, adverse outcomes of acute brain ischemia in childhood include
      death (10% of AIS children), neurological sequel, epileptic seizures (over 50%)
      and recurrence (over 20%). The knowledge of childhood stroke etiopathogenesis is
      still insufficient and the diagnostic and therapeutic procedures--controversial.
      Risk factors for childhood stroke differ from those observed in adults due to
      differing exposure to external risk factors. The most frequently reported risk
      factors for pediatric ischemic stroke are cerebral arteriopathies and vascular
      malformations, cardiac diseases, infections, traumas and metabolic diseases.
      Because of its multifactorial etiology pediatric AIS probably has a multigenic
      inheritance pattern. The genetic susceptibility to AIS may be determined by
      specific polymorphic variants encoding markers of hemostasis regulation and they
      are some of the most important targets in searching for genetic determinants in
      pediatric AIS. The authors have reviewed the recent literature on risk factors of
      childhood ischemic stroke with the focus on genetic factors like polymorphisms of
      genes encoding coagulation factors II, V, VII and XIII, MTHFR, fibrinogen beta,
      and compared them with the results performed in adult patients.

PMID- 24584519
TI  - Different mechanism of LPS-induced calcium increase in human lung epithelial cell
      and microvascular endothelial cell: a cell culture study in a model for ARDS.
AB  - Acute respiratory distress syndrome (ARDS) is a contemporary term incorporating
      the historic 'acute lung injury' and the colloquial term 'shock lung'. ARDS
      remains a serious and enigmatic human disease, causing significant mortality. The
      mechanisms involved at the alveolar cell/capillary endothelial interface have
      been explored but to date we lack clarity on the role of intracellular calcium
      ([Ca(2+)]i) fluxes across this interface. To explore the mechanisms of Ca(2+)
      induced inflammatory reaction in epithelial cells and pulmonary microvascular
      endothelial cells (HMVEC) located at the two sides of blood-air barrier, lung
      epithelial A549 and HMVEC cells were treated with LPS. Our results demonstrated
      that LPS evoked the increase of [Ca(2+)]i, TNF-alpha and IL-8 in both cells
      types. The [Ca(2+)]i increases involved intracellular but not extracellular
      Ca(2+) sources in A549, but both intracellular and extracellular Ca(2+) sources
      in HMVEC cells. The effects of LPS on both cells types were completely inhibited
      by the combination of LPS and CaSR-targeted siRNA. Furthermore, LPS-inhibited
      cell proliferations were significantly reversed by the combined treatment.
      Therefore, LPS induced different mechanisms of [Ca(2+)]i increase during the
      activation of CaSR in A549 and HMVEC cells, which translates into functional
      outputs related to ARDS. 

PMID- 24584523
TI  - Integrated care: meeting mental health needs after the Gulf oil spill.
AB  - This column describes an integrated behavioral health initiative in primary care
      clinics in Louisiana parishes affected by the Deepwater Horizon oil spill. The
      Louisiana Mental and Behavioral Health Capacity Project is an integral part of
      the Gulf Region Health Outreach Program and is funded from the Deepwater Horizon
      Medical Benefits Class Action Settlement. Using a public health approach, the
      Department of Psychiatry of the Louisiana State University Health Sciences Center
      developed an interprofessional collaboration model of care to provide culturally
      tailored and time-sensitive on-site and telemedicine services to adults and
      children affected by the disaster. Results indicate a high level of acceptance of
      the services and reductions in both mental health symptoms and general medical
      symptoms. Primary care clinic staff also report increased confidence and
      resilience to meet future disasters. The approach could be used by communities at
      risk of disasters and by rural communities with limited mental health resources. 

PMID- 24584521
TI  - Evidence-based values in housing and treatment.

PMID- 24584520
TI  - Attenuation of reserpine-induced pain/depression dyad by gentiopicroside through
      downregulation of GluN2B receptors in the amygdala of mice.
AB  - Epidemiological studies demonstrate that pain frequently occurs comorbid with
      depression. Gentiopicroside (Gent) is a secoiridoid compound isolated from
      Gentiana lutea that exhibits analgesic properties and inhibits the expression of
      GluN2B-containing N-methyl-D-aspartate (NMDA) receptors in the anterior cingulate
      cortex of mice. However, the effects of Gent on the reserpine-induced
      pain/depression dyad and its underlying mechanisms are unclear. Reserpine
      administration (1 mg/kg subcutaneous daily for 3 days) caused a significant
      decrease in the nociceptive threshold as evidenced by the reduced paw withdrawal
      latency in response to a radiant heat source and mechanical allodynia. Behavioral
      detection indicated a significant increase in immobility time during a forced
      swim test, as well as decreased time in the central area and total travel
      distance in an open field test. Furthermore, reserpinized animals exhibited
      increased oxidative stress. Systemic Gent administration dose-dependently
      ameliorated the behavioral deficits associated with reserpine-induced
      pain/depression dyad. At the same time, the decrease in biogenic amine levels
      (norepinephrine, dopamine, and serotonin) was integrated with the increase in
      caspase-3 levels and GluN2B-containing NMDA receptors in the amygdala of the
      reserpine-injected mice. Gent significantly reversed the changes in the levels of
      biogenic amines, caspase-3, and GluN2B-containing NMDA receptors in amygdala.
      However, Gent did not affect the expression of GluN2A-containing NMDA receptors.
      The inhibitory effects of Gent on oxidative stress were occluded by simultaneous
      treatment of GluN2B receptors antagonist Ro25-6981. Our study provides strong
      evidence that Gent inhibits reserpine-induced pain/depression dyad by
      downregulating GluN2B receptors in the amygdala.

PMID- 24584525
TI  - The impact of failed housing policy on the public behavioral health system.
AB  - The author describes the crisis in affordable housing for individuals with
      serious mental illness who have extremely low incomes and outlines implications
      for the behavioral health system. Studies have shown that nowhere in the United
      States can an individual with serious mental illness who is receiving
      Supplemental Security Income afford housing. This has contributed to compliance
      issues with the Americans With Disabilities Act. The failure of housing policy to
      effectively address the needs of individuals with serious mental illness who are
      in poverty is largely to blame for the most visible and costly failures
      attributed to the behavioral health system: institutionalization, incarceration,
      and chronic homelessness. It is critical for the behavioral health field to
      advocate for housing policies to address the housing affordability crisis. 

PMID- 24584524
TI  - The Washington Heights Community Service model: positive outcomes and
      implications for reimbursement under the ACA.
AB  - Medicare and the Affordable Care Act (ACA) base reimbursement partly on hospital
      readmission rates, but there is little guidance for providers to reduce these
      rates. This column describes a model of care used by Washington Heights Community
      Service (WHCS) in New York City. Without benefit of external funding, WHCS has
      implemented practices, such as family involvement at all treatment levels,
      community outreach, effective medication prescribing, shared electronic medical
      records, and proactive provider communication, that have led to lower rates of
      readmission in addition to low rates of admission and emergency room use and a
      high rate of outpatient follow-up--all particularly relevant in this era of ACA
      mandates.

PMID- 24584526
TI  - Characteristics of U.S. suicide decedents in 2005-2010 who had received mental
      health treatment.
AB  - OBJECTIVE: To inform suicide prevention efforts in mental health treatment, the
      study assessed associations between recent mental health treatment, personal
      characteristics, and circumstances of suicide among suicide decedents. METHODS:
      Data from 18 states reporting to the National Violent Death Reporting System
      between 2005 and 2010 (N=57,877 suicides) were used to compare circumstances
      among adult decedents receiving any or no type of mental health treatment within
      two months before death. RESULTS: Of suicide decedents, 28.5% received treatment
      before suicide. Several variables were associated with higher odds of receiving
      treatment, including death by poisoning with commonly prescribed substances
      (adjusted odds ratio [AOR]=3.04, 95% confidence interval [CI]=2.84-3.26), a
      history of suicide attempts (AOR=2.77, CI=2.64-2.90), depressed mood (AOR=1.69,
      CI=1.62-1.76), and nonalcoholic substance abuse or dependence (AOR=1.13, CI=1.07
      1.19). CONCLUSIONS: For nearly a third of all suicide decedents, better mental
      health care might have prevented death. Efforts to reduce access to lethal doses
      of prescription medications seem warranted to prevent overdosing with commonly
      prescribed substances.

PMID- 24584528
TI  - Health care experiences and perceived financial impact among families of children
      with an autism spectrum disorder.
AB  - OBJECTIVE: The authors compared the health care experiences of families raising a
      child with autism spectrum disorder (ASD), an intellectual disability disorder
      (IDD), or attention-deficit hyperactivity disorder (ADHD). METHODS: Children with
      a current diagnosis of ASD (N=3,005), ADHD (N=9,662), or IDD (N=949) were
      identified in the 2009-2010 National Survey of Children With Special Health Care
      Needs. Weighted structural equation modeling was used to determine the
      association between family satisfaction with medical care, timeliness of care,
      and medical insurance coverage and the impact of the child's condition on the
      family's financial situation. RESULTS: Families of children diagnosed as having
      ASD comorbid with either ADHD or IDD or comorbid with both conditions reported
      the highest levels of dissatisfaction across all health care quality variables
      and experienced the greatest impact on the family's financial situation.
      CONCLUSIONS: The findings underscore the need for comprehensive and accessible
      health care services for children with ASD, particularly those with comorbid
      conditions.

PMID- 24584527
TI  - Clinicians' utilization of child mental health telephone consultation in primary
      care: findings from Massachusetts.
AB  - OBJECTIVE: The authors examined utilization of the Massachusetts Child Psychiatry
      Access Project, a mental health telephone consultation service for primary care,
      hypothesizing that greater use would be related to severe psychiatric diagnoses
      and polypharmacy. METHODS: The authors examined the association between
      utilization, defined as the mean number of contacts per patient during the 180
      days following the initial contact (July 2008-June 2009), and characteristics of
      the initial contact, including consultation question, the child's primary mental
      health problem, psychotropic medication regimen, insurance status, and time of
      year. RESULTS: Utilization (N=4,436 initial contacts, mean=3.83 contacts) was
      associated with initial contacts about medication management, polypharmacy,
      public and private health insurance, and time of year. The child's primary mental
      health problem did not predict utilization. CONCLUSIONS: Telephone consultation
      services address treatment with psychotropic medications, particularly
      polypharmacy. Joint public-private funding should be considered for such public
      programs that serve privately insured children.

PMID- 24584529
TI  - STRoNG intervention for military families with young children.

PMID- 24584530
TI  - Caregiver depression screening in a specialty mental health clinic.

PMID- 24584546
TI  - Electric control of magnetism at the Fe/BaTiO3 interface.
AB  - Interfacial magnetoelectric coupling is a viable path to achieve electrical
      writing of magnetic information in spintronic devices. For the prototypical
      Fe/BaTiO3 system, only tiny changes of the interfacial Fe magnetic moment upon
      reversal of the BaTiO3 dielectric polarization have been predicted so far. Here,
      by using X-ray magnetic circular dichroism in combination with high-resolution
      electron microscopy and first principles calculations, we report on an
      undisclosed physical mechanism for interfacial magnetoelectric coupling in the
      Fe/BaTiO3 system. At this interface, an ultrathin oxidized iron layer exists,
      whose magnetization can be electrically and reversibly switched on and off at
      room temperature by reversing the BaTiO3 polarization. The suppression/recovery
      of interfacial ferromagnetism results from the asymmetric effect that ionic
      displacements in BaTiO3 produces on the exchange coupling constants in the
      interfacial-oxidized Fe layer. The observed giant magnetoelectric response holds
      potential for optimizing interfacial magnetoelectric coupling in view of
      efficient, low-power spintronic devices.

PMID- 24584547
TI  - Embryo selection strategy in sibling oocytes: a novel approach to measuring the
      likelihood of single-embryo transfer using a mouse embryo transfer model.
AB  - The present study investigated the effect of embryo transfer on post-implantation
      development using different fertilization approaches in sibling oocyte
      procedures. C57BL/6, DBA/2, C3H/HeJ and ICR mice were used at 8-10 weeks of age.
      Mature oocytes were collected, divided into two groups and fertilized using in
      vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). Different
      numbers of the resulting blastocysts were then transferred into recipients and
      designated as either: The single embryo transfer (SET) I model (one transferred
      embryo), the SET II model (six transferred embryos) or the multiple embryo
      transfer (MET) model (24 transferred embryos). The development efficiency, cell
      number, number of apoptotic cells in blastocysts, pregnancy efficiency, delivery
      rate and cumulative pregnancy efficiency were analyzed. IVF-fertilized embryos
      exhibited higher blastocyst development competence and embryo quality compared
      with ICSI embryos. The pregnancy and delivery efficiency was not identified to be
      significantly different between the two SET models, but it was lower in these two
      models than in the MET model. The cumulative pregnancy efficiency in SET models,
      calculated using a mathematical equation, was not decreased. In conclusion,
      embryo quality was shown to be the primary factor in selecting embryos prior to
      embryo transfer using sibling oocytes. In addition, single blastocyst transfer
      can be performed in sibling oocytes without compromising cumulative pregnancy
      rates, independent of the fertilization approach.

PMID- 24584548
TI  - Chronic reduction of GIP secretion alleviates obesity and insulin resistance
      under high-fat diet conditions.
AB  - Gastric inhibitory polypeptide (GIP) exhibits potent insulinotropic effects on
      beta-cells and anabolic effects on bone formation and fat accumulation. We
      explored the impact of reduced GIP levels in vivo on glucose homeostasis, bone
      formation, and fat accumulation in a novel GIP-GFP knock-in (KI) mouse. We
      generated GIP-GFP KI mice with a truncated prepro-GIP gene. The phenotype was
      assessed in heterozygous and homozygous states in mice on a control fat diet and
      a high-fat diet (HFD) in vivo and in vitro. Heterozygous GIP-GFP KI mice (GIP
      reduced mice [GIP(gfp/+)]) exhibited reduced GIP secretion; in the homozygous
      state (GIP-lacking mice [GIP(gfp/gfp)]), GIP secretion was undetectable. When fed
      standard chow, GIP(gfp/+) and GIP(gfp/gfp) mice showed mild glucose intolerance
      with decreased insulin levels; bone volume was decreased in GIP(gfp/gfp) mice and
      preserved in GIP(gfp/+) mice. Under an HFD, glucose levels during an oral glucose
      tolerance test were similar in wild-type, GIP(gfp/+), and GIP(gfp/gfp) mice,
      while insulin secretion remained lower. GIP(gfp/+) and GIP(gfp/gfp) mice showed
      reduced obesity and reduced insulin resistance, accompanied by higher fat
      oxidation and energy expenditure. GIP-reduced mice demonstrate that partial
      reduction of GIP does not extensively alter glucose tolerance, but it alleviates
      obesity and lessens the degree of insulin resistance under HFD conditions,
      suggesting a potential therapeutic value. 

PMID- 24584549
TI  - Sitagliptin, a DPP-4 inhibitor, acutely inhibits intestinal lipoprotein particle
      secretion in healthy humans.
AB  - The dipeptidyl peptidase-4 inhibitor sitagliptin, an antidiabetic agent, which
      lowers blood glucose levels, also reduces postprandial lipid excursion after a
      mixed meal. The underlying mechanism of this effect, however, is not clear. This
      study examined the production and clearance of triglyceride-rich lipoprotein
      particles from the liver and intestine in healthy volunteers in response to a
      single oral dose of sitagliptin. Using stable isotope tracer techniques and with
      control of pancreatic hormone levels, the kinetics of lipoprotein particles of
      intestinal and hepatic origin were measured. Compared with placebo, sitagliptin
      decreased intestinal lipoprotein concentration by inhibiting particle production,
      independent of changes in pancreatic hormones, and circulating levels of glucose
      and free fatty acids. Fractional clearance of particles of both intestinal and
      hepatic origin, and production of particles of hepatic origin, were not affected.
      This pleiotropic effect of sitagliptin may explain the reduction in postprandial
      lipemia seen in clinical trials of this agent and may provide metabolic benefits
      beyond lowering of glucose levels. 

PMID- 24584550
TI  - Impact of acute hyperglycemia on myocardial infarct size, area at risk, and
      salvage in patients with STEMI and the association with exenatide treatment:
      results from a randomized study.
AB  - Hyperglycemia upon hospital admission in patients with ST-segment elevation
      myocardial infarction (STEMI) occurs frequently and is associated with adverse
      outcomes. It is, however, unsettled as to whether an elevated blood glucose level
      is the cause or consequence of increased myocardial damage. In addition, whether
      the cardioprotective effect of exenatide, a glucose-lowering drug, is dependent
      on hyperglycemia remains unknown. The objectives of this substudy were to
      evaluate the association between hyperglycemia and infarct size, myocardial
      salvage, and area at risk, and to assess the interaction between exenatide and
      hyperglycemia. A total of 210 STEMI patients were randomized to receive
      intravenous exenatide or placebo before percutaneous coronary intervention.
      Hyperglycemia was associated with larger area at risk and infarct size compared
      with patients with normoglycemia, but the salvage index and infarct size
      adjusting for area at risk did not differ between the groups. Treatment with
      exenatide resulted in increased salvage index both among patients with
      normoglycemia and hyperglycemia. Thus, we conclude that the association between
      hyperglycemia upon hospital admission and infarct size in STEMI patients is a
      consequence of a larger myocardial area at risk but not of a reduction in
      myocardial salvage. Also, cardioprotection by exenatide treatment is independent
      of glucose levels at hospital admission. Thus, hyperglycemia does not influence
      the effect of the reperfusion treatment but rather represents a surrogate marker
      for the severity of risk and injury to the myocardium. 

PMID- 24584552
TI  - Emission enhancement of sound emitters using an acoustic metamaterial cavity.
AB  - The emission enhancement of sound without electronic components has wide
      applications in a variety of remote systems, especially when highly miniaturized
      (smaller than wavelength) structures can be used. The recent advent of acoustic
      metamaterials has made it possible to realize this. In this study, we propose,
      design, and demonstrate a new class of acoustic cavity using a double-walled
      metamaterial structure operating at an extremely low frequency. Periodic zigzag
      elements which exhibit Fabry-Perot resonant behavior below the phononic band-gap
      are used to yield strong sound localization within the subwavelength gap, thus
      providing highly effective emission enhancement. We show, both theoretically and
      experimentally, 10 dB sound emission enhancement near 1060 Hz that corresponds to
      a wavelength approximately 30 times that of the periodicity. We also provide a
      general guideline for the independent tuning of the quality factor and effective
      volume of acoustic metamaterials. This approach shows the flexibility of our
      design in the efficient control of the enhancement rate.

PMID- 24584551
TI  - Increased interaction with insulin receptor substrate 1, a novel abnormality in
      insulin resistance and type 2 diabetes.
AB  - Insulin receptor substrate 1 (IRS1) is a key mediator of insulin signal
      transduction. Perturbations involving IRS1 complexes may lead to the development
      of insulin resistance and type 2 diabetes (T2D). Surprisingly little is known
      about the proteins that interact with IRS1 in humans under health and disease
      conditions. We used a proteomic approach to assess IRS1 interaction partners in
      skeletal muscle from lean healthy control subjects (LCs), obese insulin-resistant
      nondiabetic control subjects (OCs), and participants with T2D before and after
      insulin infusion. We identified 113 novel endogenous IRS1 interaction partners,
      which represents the largest IRS1 interactome in humans and provides new targets
      for studies of IRS1 complexes in various diseases. Furthermore, we generated the
      first global picture of IRS1 interaction partners in LCs, and how they differ in
      OCs and T2D patients. Interestingly, dozens of proteins in OCs and/or T2D
      patients exhibited increased associations with IRS1 compared with LCs under the
      basal and/or insulin-stimulated conditions, revealing multiple new dysfunctional
      IRS1 pathways in OCs and T2D patients. This novel abnormality, increased
      interaction of multiple proteins with IRS1 in obesity and T2D in humans, provides
      new insights into the molecular mechanism of insulin resistance and identifies
      new targets for T2D drug development.

PMID- 24584553
TI  - Microdebrider cavitation and transcervical removal of parapharyngeal schwannomas
      approaching the skull base.
AB  - Removal of parapharyngeal space (PPS) schwannomas approaching the skull base
      through a purely transcervical approach requires adequate visualization of the
      surgical field to obtain complete resection with minimal sequelae. This is a
      retrospective series of four patients undergoing transcervical removal of
      sympathetic chain PPS schwannomas abutting the skull base by an intracapsular
      microdebrider tumor cavitation. Radiologic data, complications, functional
      outcomes, and follow-up status were considered. MRI was suggestive of PPS
      schwannoma in all cases, and correctly predicted the nerve of origin in three out
      of four cases. All patients developed postoperative Claude Bernard-Horner and
      first-bite syndromes. One patient also presented temporary neuropraxia of the IX
      cranial nerve, and another of the IX and X cranial nerves. Microdebrider
      cavitation of sympathetic chain PPS schwannoma abutting the skull base proved to
      be a reliable technique allowing good visualization of adjacent neural and
      vascular structures through a purely transcervical approach, while maintaining a
      low complication rate.

PMID- 24584563
TI  - The effect of weight loss on OSA severity and position dependence in the
      bariatric population.
AB  - BACKGROUND: The aims of this study were to determine the prevalence of positional
      obstructive sleep apnea (POSA) in patients undergoing bariatric surgery and to
      evaluate the effect of weight loss brought about by bariatric surgery on POSA.
      Furthermore, the authors investigated whether body mass index (BMI), neck
      circumference, apnea-hypopnea index (AHI), and age are predictors for POSA.
      METHOD: A retrospective cohort study was conducted with data collected from
      patients who were screened for OSA pre-bariatric surgery and completed a follow
      up polysomnography post bariatric surgery from August 2008 to November 2012.
      Descriptive statistics were used to characterize the prevalence of POSA patients,
      and the Mann-Whitney and Wilcoxon signed-rank tests were used to examine
      differences between the POSA and non-POSA groups. A logistic regression model was
      used to determine predictors for POSA. RESULTS: Thirty-four percent of patients
      had POSA, which is significantly lower (p<0.001) than in the general population.
      BMI, neck circumference, and AHI were significantly lower in POSA patients. AHI
      was the only significant independent predictor for POSA. Of the 91 patients
      analyzed following bariatric surgery, 35.2% (n=32) no longer had OSA. CONCLUSION:
      The prevalence of POSA in patients undergoing bariatric surgery is significantly
      lower than the prevalence noted in the general population. A low AHI was shown to
      be the only significant independent predictor for the presence of POSA.

PMID- 24584564
TI  - The influence of nasal abnormalities in adherence to continuous positive airway
      pressure device therapy in obstructive sleep apnea patients. What role does the
      nose play?

PMID- 24584566
TI  - Parkinsonism as an initial manifestation of rheumatoid meningitis.

PMID- 24584565
TI  - Effects of electromagnetic fields on reelin and Dab1 expression in the developing
      cerebral cortex.
AB  - Many studies describe the biological effects of electromagnetic fields (EMF)
      including brain damages, neuronal migration and neurogenesis within the central
      nervous system. Neuronal cell produced in the neuroepithelium migrates along
      radial glial fibers into the cortical plate. Reelin, which is produced by Cajal
      Retzius cells directs neuronal migration. It was shown that Disabled 1 (Dab1)
      functions downstream of reelin signal transduction pathway that directs the
      correct cytoarchitecture of the developing cortex. In this study, the EMF effects
      on total protein concentration (TPC), reelin and Dab1 expression in the
      developing cortex was studied. 30 pregnant Balb/c mice were separated into three
      groups: control (n = 10), EMF (n = 10) and SHAM groups (n = 10). The 15-day
      pregnant mice were placed inside the solenoid for a daily EMF exposure of 5 h for
      3 consecutive days (15-17). The SHAM group was also located in the same coil with
      no exposure. Mice were sacrificed 24 h after the final exposure session. TPC,
      reelin and Dab1 expression were studied by Bio-Rad protein assay and western
      blot. No significant change in the TPC was seen in the EMF-treated cerebral
      cortex samples compared with those from the SHAM and control groups. It was also
      shown that the reelin and Dab1 expression increases in the EMF-treated cerebral
      cortex extracts as compared to controls and SHAM group. It is concluded that EMF
      may play important role in the neural cell migration by increasing reelin and
      Dab1 expression in the developing cortex.

PMID- 24584567
TI  - The association between clinical parameters and glaucoma-specific quality of life
      in Chinese primary open-angle glaucoma patients.
AB  - OBJECTIVE. To investigate the association between clinical measurements and
      glaucoma-specific quality of life in Chinese glaucoma patients. DESIGN. Cross
      sectional study. SETTING. An academic hospital in Hong Kong. PATIENTS. A Chinese
      translation of the Glaucoma Quality of Life-15 questionnaire was completed by 51
      consecutive patients with bilateral primary open-angle glaucoma. The binocular
      means of several clinical measurements were correlated with Glaucoma Quality of
      Life-15 findings using Pearson's correlation coefficient and linear regression.
      The measurements were the visual field index and pattern standard deviation from
      the Humphrey Field Analyzer, Snellen best-corrected visual acuity, presenting
      intra-ocular pressure, current intra-ocular pressure, average retinal nerve fibre
      layer thickness via optical coherence tomography, and the number of topical anti
      glaucoma medications being used. RESULTS. In these patients, there was a
      significant correlation and linear relationship between a poorer Glaucoma Quality
      of Life-15 score and a lower visual field index (r=0.3, r(2)=0.1, P=0.01) and
      visual acuity (r=0.3, r(2)=0.1, P=0.03). A thinner retinal nerve fibre layer also
      correlated with a poorer Glaucoma Quality of Life-15 score, but did not attain
      statistical significance (r=0.3, P=0.07). There were no statistically significant
      correlations for the other clinical parameters with the Glaucoma Quality of Life
      15 scores (all P values being >0.7). The three most problematic activities
      affecting quality of life were "adjusting to bright lights", "going from a light
      to a dark room or vice versa", and "seeing at night". CONCLUSION. For Chinese
      primary open-angle glaucoma patients, binocular visual field index and visual
      acuity correlated linearly with glaucoma-specific quality of life, and activities
      involving dark adaptation were the most problematic. 

PMID- 24584569
TI  - Dielectric properties of barium titanate supramolecular nanocomposites.
AB  - Nanostructured dielectric composites can be obtained by dispersing high
      permittivity fillers, barium titanate (BTO) nanocubes, within a supramolecular
      framework. Thin films of BTO supramolecular nanocomposites exhibit a dielectric
      permittivity (epsilonr) as high as 15 and a relatively low dielectric loss of
      ~0.1 at 1 kHz. These results demonstrate a new route to control the dispersion of
      high permittivity fillers toward high permittivity dielectric nanocomposites with
      low loss. Furthermore, the present study shows that the size distribution of
      nanofillers plays a key role in their spatial distribution and local ordering and
      alignment within supramolecular nanostructures. 

PMID- 24584568
TI  - Lateral epicondylalgia: midlife crisis of a tendon.
AB  - The pathogenesis and management of lateral epicondylalgia, or tennis elbow, a
      common ailment affecting middle-aged subjects of both genders continue to provoke
      controversy. Currently it is thought to be due to local tendon pathology, pain
      system changes, and motor system impairment. Its diagnosis is usually clinical,
      based on a classical history, as well as symptoms and signs. In selected cases,
      additional imaging (X-rays, ultrasound, and magnetic resonance imaging) can help
      to confirm the diagnosis. Different treatment modalities have been described,
      including the use of orthotics, non-steroidal anti-inflammatory drugs, steroid
      injections, topical glyceryl trinitrate, exercise therapy, manual therapy,
      ultrasound therapy, laser therapy, extracorporeal shockwave therapy, acupuncture,
      taping, platelet-rich plasma injections, hyaluronan gel injections, botulinum
      toxin injections, and surgery. Nevertheless, evidence to select the best
      treatment is lacking and the choice of therapy depends on the experience of the
      management team, availability of the equipment and expertise, and patient
      response. This article provides a snapshot of current medical practice for
      lateral epicondylalgia management. 

PMID- 24584570
TI  - Rbm20-deficient cardiogenesis reveals early disruption of RNA processing and
      sarcomere remodeling establishing a developmental etiology for dilated
      cardiomyopathy.
AB  - Dilated cardiomyopathy (DCM) due to mutations in RBM20, a gene encoding an RNA
      binding protein, is associated with high familial penetrance, risk of progressive
      heart failure and sudden death. Although genetic investigations and physiological
      models have established the linkage of RBM20 with early-onset DCM, the underlying
      basis of cellular and molecular dysfunction is undetermined. Modeling human
      genetics using a high-throughput pluripotent stem cell platform was herein
      designed to pinpoint the initial transcriptome dysfunction and mechanistic
      corruption in disease pathogenesis. Tnnt2-pGreenZeo pluripotent stem cells were
      engineered to knockdown Rbm20 (shRbm20) to determine the cardiac-pathogenic
      phenotype during cardiac differentiation. Intracellular Ca(2+) transients
      revealed Rbm20-dependent alteration in Ca(2+) handling, coinciding with known
      pathological splice variants of Titin and Camk2d genes by Day 24 of
      cardiogenesis. Ultrastructural analysis demonstrated elongated and thinner
      sarcomeres in the absence of Rbm20 that is consistent with human cardiac biopsy
      samples. Furthermore, Rbm20-depleted transcriptional profiling at Day 12
      identified Rbm20-dependent dysregulation with 76% of differentially expressed
      genes linked to known cardiac pathology ranging from primordial Nkx2.5 to mature
      cardiac Tnnt2 as the initial molecular aberrations. Notably, downstream
      consequences of Rbm20-depletion at Day 24 of differentiation demonstrated
      significant dysregulation of extracellular matrix components such as the
      anomalous overexpression of the Vtn gene. By using the pluripotent stem cell
      platform to model human cardiac disease according to a stage-specific cardiogenic
      roadmap, we established a new paradigm of familial DCM pathogenesis as a
      developmental disorder that is patterned during early cardiogenesis and
      propagated with cellular mechanisms of pathological cardiac remodeling. 

PMID- 24584572
TI  - ARPKD and early manifestations of ADPKD: the original polycystic kidney disease
      and phenocopies.
AB  - Renal cysts are clinically and genetically heterogeneous conditions. Polycystic
      kidney disease (PKD) is common and its characterization has paved the way for the
      identification of a growing number of cilia-related disorders (ciliopathies) of
      which most show cystic kidneys. While the recessive form of PKD (ARPKD) virtually
      always presents in childhood, early onset can, in some instances, also occur in
      the dominant form (ADPKD). Both ADPKD genes (PKD1 and PKD2) can also be inherited
      in a recessive way, making the story more complex with evidence for a dosage
      sensitive network. Several phenocopies are known, and mutations in HNF1beta or
      genes that typically cause other ciliopathies, such as nephronophthisis, Bardet
      Biedl, Joubert syndrome and related disorders, can mimic PKD. An accurate genetic
      diagnosis is crucial for genetic counseling, prenatal diagnostics, and the
      clinical management of patients and their families. The increasing number of
      genes that have to be considered in patients with cystic kidney disease is
      challenging to address by conventional techniques and largely benefits from next
      generation sequencing-based approaches. The parallel analysis of targeted genes
      considerably increases the detection rate, allows for better interpretation of
      identified variants, and avoids genetic misdiagnoses. 

PMID- 24584573
TI  - ortho-Dihydroxyl-9,10-anthraquinone dyes as visible-light sensitizers that
      exhibit a high turnover number for hydrogen evolution.
AB  - Pt/TiO2 sensitized by the cheap and organic ortho-dihydroxyl-9,10-anthraquinone
      dyes, such as Alizarin and Alizarin Red, achieved a TON of approximately 10 000
      (TOF > 250 h(-1) for the first ten hours) during >80 hours of visible light
      irradiation (>420 nm) for photocatalytic hydrogen evolution when triethanolamine
      was used as the sacrificial donor. The stability and activity enhancements can be
      attributed to the two highly serviceable redox reactions involving the 9,10
      dicarbonyl and ortho-dihydroxyl groups of the anthracene ring, respectively. 

PMID- 24584571
TI  - Inherited mitochondrial DNA variants can affect complement, inflammation and
      apoptosis pathways: insights into mitochondrial-nuclear interactions.
AB  - Age-related macular degeneration (AMD) is the leading cause of vision loss in
      developed countries. While linked to genetic polymorphisms in the complement
      pathway, there are many individuals with high risk alleles that do not develop
      AMD, suggesting that other 'modifiers' may be involved. Mitochondrial (mt)
      haplogroups, defined by accumulations of specific mtDNA single nucleotide
      polymorphisms (SNPs) which represent population origins, may be one such
      modifier. J haplogroup has been associated with high risk for AMD while the H
      haplogroup is protective. It has been difficult to assign biological consequences
      for haplogroups so we created human ARPE-19 cybrids (cytoplasmic hybrids), which
      have identical nuclei but mitochondria of either J or H haplogroups, to
      investigate their effects upon bioenergetics and molecular pathways. J cybrids
      have altered bioenergetic profiles compared with H cybrids. Q-PCR analyses show
      significantly lower expression levels for seven respiratory complex genes encoded
      by mtDNA. J and H cybrids have significantly altered expression of eight nuclear
      genes of the alternative complement, inflammation and apoptosis pathways.
      Sequencing of the entire mtDNA was carried out for all the cybrids to identify
      haplogroup and non-haplogroup defining SNPs. mtDNA can mediate cellular
      bioenergetics and expression levels of nuclear genes related to complement,
      inflammation and apoptosis. Sequencing data suggest that observed effects are not
      due to rare mtDNA variants but rather the combination of SNPs representing the J
      versus H haplogroups. These findings represent a paradigm shift in our concepts
      of mt-nuclear interactions. 

PMID- 24584574
TI  - Acclimation of hydrogen peroxide enhances salt tolerance by activating defense
      related proteins in Panax ginseng C.A. Meyer.
AB  - The effect of exogenously applied hydrogen peroxide on salt stress tolerance was
      investigated in Panax ginseng. Pretreatment of ginseng seedlings with 100 MUM
      H2O2 increased the physiological salt tolerance of the ginseng plant and was used
      as the optimum concentration to induce salt tolerance capacity. Treatment with
      exogenous H2O2 for 2 days significantly enhanced salt stress tolerance in ginseng
      seedlings by increasing the activities of ascorbate peroxidase, catalase and
      guaiacol peroxidase and by decreasing the concentrations of malondialdehyde (MDA)
      and endogenous H2O2 as well as the production rate of superoxide radical (O2(-)).
      There was a positive physiological effect on the growth and development of salt
      stressed seedlings by exogenous H2O2 as measured by ginseng dry weight and both
      chlorophyll and carotenoid contents. Exogenous H2O2 induced changes in MDA, O2(
      ), antioxidant enzymes and antioxidant compounds, which are responsible for
      increases in salt stress tolerance. Salt treatment caused drastic declines in
      ginseng growth and antioxidants levels; whereas, acclimation treatment with H2O2
      allowed the ginseng seedlings to recover from salt stress by up-regulation of
      defense-related proteins such as antioxidant enzymes and antioxidant compounds.

PMID- 24584575
TI  - Gene cloning and expression analysis of IRF1 in half-smooth tongue sole
      (Cynoglossus semilaevis).
AB  - Interferon regulatory factor 1 (IRF1) was known to play key roles in antiviral
      defense in several species, and some other important biological processes. In
      this report, full length cDNA of IRF1 from Cynoglossus semilaevis (CsIRF1) was
      identified. It was of 1,455 bp, containing a 5' UTR of 104 bp, a 3' UTR of 541 bp
      with a poly (A) tail and an ORF of 810 bp encoding a putative protein of 269
      amino acids. The putative CsIRF1protein contained one conserved IRF domain (1
      113aa), and two low complexity regions (140-158aa and 230-242aa, respectively).
      Phylogenetic analysis showed that CsIRF1 was conserved in the teleost
      evolutionary branch, which was independent of mammalian, birds and amphibians.
      Additionally, CsIRF1 had the 96% homology with marine fishes, while 66% with
      freshwater fishes. The expression profiles of CsIRF1was analyzed by quantitative
      real-time PCR in healthy tissues and in immune tissues challenged with different
      pathogens [Vibrio anguillarum and Lymphocystis disease virus (LCDV)],
      respectively. CsIRF1 was widely expressed in healthy tissues of Cynoglossus
      semilaevis and with the highest expression in blood, as much as 19 times of that
      in liver. V. anguillarum and LCDV both induced the CsIRF1 gene expression
      distinctly in liver, with the peak value reached to 98-fold at 6 h and 25-fold at
      24 h, respectively. The bacteria induced CsIRF1 suddenly up-expression in each
      detected tissues. However, at the initial stage of the challenge of virus LCDV,
      the CsIRF1 expression in blood and spleen were up regulated; on the contrary, its
      expression in liver and head kidney were down regulated, 0.3 and 0.4-fold 6 h
      post virus injection, respectively. These results suggested that CsIRF1 gene
      might involve in not only antiviral activity but also antibacterial procedure,
      indicating its vital role in Cynoglossus semilaevis innate defense system.

PMID- 24584576
TI  - Population structure and genetic diversity analysis of Indian and exotic rice
      (Oryza sativa L.) accessions using SSR markers.
AB  - In order to understand the population structure and genetic diversity among a set
      of 82 rice genotypes collected from different parts of the Asian countries
      including India were characterized using 39 microsatellite loci. The Population
      structure analysis suggested that the optimum number of subpopulations was four
      (K = 4) among the rice genotypes, whereas phylogenetic analysis grouped them into
      three populations. The results obtained from phylogenetic and STRUCTURE analysis
      proved to be very powerful for the differentiation of rice genotypes based on
      their place of origin. The genetic diversity analysis using 39 SSR loci yielded
      183 scorable alleles, out of which 182 alleles were observed to be polymorphic
      with an average of 4.8 alleles per locus. The Polymorphism Information Content
      (PIC) values for all the polymorphic primers across 82 rice genotypes varied from
      0.02 to 0.77, with an average of 0.50. Gene diversity (He) was found to be in the
      range of 0.02 (RM484) to 0.80 (OSR13) with an average value of 0.55, while
      heterozygosity (Ho) was observed with an average of 0.07, ranging from 0.01
      (RM334) to 0.31 (RM316). The present study resulted in identification of seven
      highly polymorphic SSR loci viz., OSR13, RM152, RM144, RM536, RM489, RM259 and
      RM271 based on the parameters like PIC value (>= 0.70), gene diversity (>= 0.71),
      and polymorphic alleles (>= 6). These seven polymorphic primers can effectively
      be used in further molecular breeding programs and QTL mapping studies of rice
      since they exhibited very high polymorphism over other loci. SSR analysis
      resulted in a more definitive separation of clustering of genotypes indicating a
      higher level of efficiency of SSR markers for the accurate determination of
      relationships between accessions.

PMID- 24584582
TI  - Sodium superionic conduction in Na2B12H12.
AB  - Impedance measurements indicate that Na2B12H12 exhibits dramatic Na(+)
      conductivity (on the order of 0.1 S cm(-1)) above its order-disorder phase
      transition at ~529 K, rivaling that of current, solid-state, ceramic-based, Na
      battery electrolytes. Superionicity may be aided by the large size,
      quasispherical shape, and high rotational mobility of the B12H12(2-) anions. 

PMID- 24584577
TI  - Cloning and analysis of a functional promoter of fungal immunomodulatory protein
      from Flammulina velutipes.
AB  - Fugal immunomodulatory protein from Flammulina velutipes (FIP-fve) belongs to
      FIPs family, which has precious pharmaceutical value. To understand the
      regulatory mechanism of FIP-fve expression, we have cloned a 900 bp genomic DNA
      fragment from the transcriptional start site of the FIP-fve gene using genomic
      walker technology. Sequence analysis showed the presence of several eukaryotic
      transcription factor binding motifs in the 900 bp of upstream region of the FIP
      fve gene, which contains one putative TATA-boxes, four possible CAAT-boxes, one
      ABRE, one ARE, three CGTCA-motifs, two TGA-elements and four Skn-1 motifs. The
      eukaryotic expression vector pfveP:: GUS-GFP was transferred into tobacco via an
      agrobacterium-mediated leaf disc transformation. The results showed that the FIP
      fve promoter could induce the reporter gene GUS or GFP expression in different
      tissues of tobaccos. This study would lay a foundation for expression regulation
      of FIP-fve and development of genetic-modified plant products.

PMID- 24584583
TI  - Comparison of a very low-calorie-ketogenic diet with a standard low-calorie diet
      in the treatment of obesity.
AB  - The global prevalence of obesity has significantly increased in most
      industrialized countries. Anti-obesity drugs are scarce, and indications to
      change their life style are impractical. Therefore, to identify diets able to
      produce significantly and maintained weight loss is mandatory. The present work
      evaluated the efficacy of a very low-calorie-ketogenic (VLCK) diet in obesity. A
      group of obese patients were randomized into two groups: the VLCK diet group and
      a standard low-calorie diet (LC group). The follow-up period was 12 months. Both
      groups received external support, counseling, to perform physical activity and
      adhered to the diet. The VLCK diet induced a 30-45 days of mild ketosis and
      significant effects on body weight within 15 days. At 2 months, the weight
      reductions in the VLCK diet and LC diet groups were 13.6 +/- 3.9 and 4.8 +/- 2.7
      kg, respectively (p < 0.0001). At the end of the study, at 12 months, the weight
      reductions were 19.9 +/- 12.3 and 7.0 +/- 5.6 kg, respectively (p < 0.0001), and
      more than 88 % of patients in the VLCK diet group lost more of 10 % of their
      initial weight. Lean mass was practically unaffected. The VLCK diet was well
      tolerated and the side effects were moderate and transitory. In a group of obese
      patients, the VLCK diet was significantly more effective than a standard LC diet.
      At one year follow-up in the group with VLCK diet, most of the patients loss more
      than 10 % of their initial weight and lean mass was well preserved.

PMID- 24584584
TI  - Berberine induces double-strand DNA breaks in Rev3 deficient cells.
AB  - Berberine is a natural isoquinoline alkaloid, the majority of which is extracted
      from Huang Lian and other medicinal herbs. Numerous studies have revealed that
      berberine exhibits anticancer activity, however the mechanisms underlying this
      effect remain elusive. To examine these mechanisms, we analyzed the effects of
      berberine on a panel of DNA repair deficient chicken B lymphocyte (DT40) clones.
      Our results revealed that DT40 cells deficient in Rev3 (Rev3-/-), a translesion
      DNA synthesis (TLS) gene, were hypersensitive to berberine. Following berberine
      treatment, cell cycle analysis identified that G2/M arrest was increased in Rev3
      /- cells. Furthermore, compared with wild-type cells (WT), berberine also induced
      a significant increase in double-strand breaks (DSBs) in Rev3-/- cells, as
      revealed by chromosomal aberration (CA) analysis. These results suggest that
      berberine is able to induce DNA damage, and that the Rev3 associated DNA repair
      pathway participates in the processes that aid its repair.

PMID- 24584585
TI  - Rest breaks--a countermeasure for work-related injuries?

PMID- 24584586
TI  - Residual and cumulative effects of soil application of sewage sludge on corn
      productivity.
AB  - The objective of this study was to evaluate the effect of frequent and periodic
      applications of sewage sludge to the soil, on corn productivity. The experiment
      was carried out as part of an experiment that has been underway since 1999, using
      two types of sludge. One came from the Barueri Sewage Treatment Station (BS,
      which receives both household and industrial sludge) and the other came from the
      Franca Sewage Treatment Station (FS, which receives only household sludge). The
      Barueri sludge was applied from 1999 up to the agricultural year of 2003/2004.
      With the exception of the agricultural years of 2004/2005 and 2005/2006, the
      Franca sludge was applied up to 2008/2009. All the applications were made in
      November, with the exception of the first one which was made in April 1999. After
      harvesting the corn, the soil remained fallow until the next cultivation. The
      experiment was set up as a completely randomized block design with three
      replications and the following treatments: control without chemical fertilization
      or sludge application, mineral fertilization, and dose 1 and dose 2 of sludge
      (Franca and Barueri). The sludges were applied individually. Dose 1 was
      calculated by considering the recommended N application for corn. Dose 2 was
      twice dose 1. It was evident from this work that the successive application of
      sludge to the soil in doses sufficient to reach the productivity desired with the
      use of nitrogen fertilizers could cause environmental problems due to N losses to
      the environment and that the residual and cumulative effects should be considered
      when calculating the application of sludge to soil. 

PMID- 24584587
TI  - Pollutant concentration profile reconstruction using digital soft sensors for
      biodegradation and exposure assessment in the presence of model uncertainty.
AB  - A new approach to the problem of environmental hazard assessment and monitoring
      for pollutant biodegradation reaction systems in the presence of uncertainty is
      proposed using soft sensor-based pollutant concentration dynamic profile
      reconstruction techniques. In particular, a robust reduced-order soft sensor is
      proposed that can be digitally implemented in the presence of inherent complexity
      and the inevitable model uncertainty. The proposed method explicitly incorporates
      all the available information associated with a process model characterized by
      varying degrees of uncertainty, as well as available sensor measurements of
      certain physicochemical quantities. Based on the above information, a reduced
      order soft sensor is designed enabling the reliable reconstruction of pollutant
      concentration profiles in complex biodegradation systems that can not be always
      achieved due to physical and/or technical limitations associated with current
      sensor technology. The option of using the aforementioned approach to compute
      toxic load and persistence indexes on the basis of the reconstructed
      concentration profiles is also pursued. Finally, the performance of the proposed
      method is evaluated in two illustrative environmental hazard assessment case
      studies. 

PMID- 24584590
TI  - Economically oriented process optimization in waste management.
AB  - A brief report on the development of novel apparatus is presented. It was
      verified in a commercial scale that a new concept of anaerobic fermentation
      followed by continuous pyrolysis is technically and economically feasible to
      manage previously enzymatically hydrolyzed waste haylage in huge volumes. The
      design of the concept is thoroughly described, documented in figures, and
      biochemically analyzed in detail. Assessment of the concept shows that subsequent
      pyrolysis of the anaerobically fermented residue allows among biogas to produce
      also high-quality biochar. This significantly improves the overall economy. In
      addition, it may be assumed that this applied research is consistent with
      previous theoretical assumptions stating that any kind of aerobic or anaerobic
      fermentation increases the microporosity of the biochar obtained. 

PMID- 24584589
TI  - Selected current-use pesticides (CUPs) in coastal and offshore sediments of Bohai
      and Yellow seas.
AB  - China is one of the largest producers, consumers, and traders for pesticides in
      the world. Currently, there are more than 600 pesticide-active substances
      registered in China, whereas few studies were conducted to improve our
      understanding of the occurrence and environmental impact of current-use
      pesticides (CUPs) in China's environment. In this work, 72 surface sediment
      samples were taken from the coastal and offshore of Bohai and Yellow seas and
      were analyzed for six CUPs (trifluralin, dacthal, quintozene, endosulfan,
      chlorpyrifos, and dicofol) and two metabolites (pentachloroanisole and endosulfan
      sulfate). Sediment samples were categorized as estuarine or near-shore sediments
      (Laizhou Bay, Taozi Bay, Sishili Bay, and Jiaozhou Bay) and offshore sediments.
      Trifluralin, alpha-endosulfan, endosulfan sulfate, chlorpyrifos, dicofol, and
      pentachloroanisole were detected in more than 60 % of the samples. Dicofol was
      the predominant compound with concentrations mostly higher than 100 pg/g dry
      weight (dw) with the highest concentration of 18,000 pg/g dw. Concentrations of
      other compounds were mainly below 100 pg/g dw. CUP levels were much lower than
      the sediment screening benchmark calculated. The highest levels of alpha
      endosulfan, endosulfan sulfate, trifluralin, and chlorpyrifos existed at Laizhou
      Bay, whereas pentachloroanisole and dicofol had highest mean concentrations at
      Jiaozhou Bay. Generally, no correlation between pesticide concentrations and
      total organic carbon was observed either for offshore samples or for near-shore
      samples.

PMID- 24584591
TI  - Kocuria species peritonitis: although rare, we have to care.
AB  - Kocuria species are found in the environment and on human skin. These micro
      organisms are generally considered to be nonpathogenic saprophytes, rarely
      causing infection. However, the peritoneum has been reported to be a site of
      Kocuria infection. We reviewed all cases of peritonitis in peritoneal dialysis
      (PD) patients caused by Kocuria species that were reported in the worldwide
      literature. In total, 12 episodes of Kocuria species peritonitis have been
      reported in 9 PD patients. The median age of the patients was 62 years (range: 8 
      78 years). In the reported episodes, 4 different Kocuria species were isolated,
      with K. varians being the predominant species (41.7%). The most common initial
      symptom was abdominal pain (83.3%), followed by turbid effluent (75%) and fever
      (33.3%). Intraperitoneal first-generation cephalosporins and glycopeptides were
      the most-used antibiotics, with first-generation cephalosporins being more often
      preferred as first-line therapy. The median duration of treatment was 14 days,
      and in 2 episodes, the Tenckhoff catheter was removed. Although Kocuria
      peritonitis in PD patients is rare, it should be promptly treated because
      relapses can occur, especially with K. varians episodes. 

PMID- 24584592
TI  - Microbiology and outcomes of peritonitis in northern India.
AB  - BACKGROUND: Peritoneal dialysis (PD) is an established treatment modality for end
      stage renal disease (ESRD). Peritonitis remains a serious complication in PD
      patients and an important cause of drop-out from the program. Types of pathogens
      and their drug resistance patterns may determine the outcome of peritonitis. The
      present study was undertaken to determine the microbiology of peritonitis in PD
      patients, antibiotic resistance in commonly isolated bacterial pathogens and
      clinical outcomes. METHOD: We enrolled 211 patients with ESRD undergoing PD who
      developed peritonitis during 2002 to 2011. PD fluids were cultured and antibiotic
      susceptibility test of the bacterial isolates was performed. RESULT: A total of
      303 peritonitis episodes with an overall incidence of 0.41 episodes per patient
      year were recorded. Gram-positive, gram-negative, fungi, Mycobacterium
      tuberculosis and >= 2 organisms were isolated from 102 (33.7%), 89 (29.4%), 41
      (13.5%), 11 (3.6%) and five (1.6%) episodes respectively; 55 (18.2%) episodes
      were culture negative. Coagulase-negative Staphylococcus spp. (CONS) was the most
      common isolate. Catheter loss and hospital admission in gram-negative peritonitis
      were significantly higher than in gram-positive peritonitis (36/89 (40.4%) vs
      20/102 (19.6%), p < 0.001; and 56/89 (62.9%) vs 42/102 (41.2%), p = 0.004
      respectively). Antibiotic susceptibility tests showed 54.3% of Enterobacteriaceae
      isolates were extended spectrum beta-lactamase (ESBL) producers, 23.5% of
      Acinetobacter species and 11.5% of Pseudomonas aeruginosa were metallo-beta
      lactamase (MBL) producers; 15.4% of enterococci and 28.6% of staphylococci were
      resistant to vancomycin and methicillin respectively. Mortality was significantly
      higher in patients having peritonitis due to vancomycin-resistant enterococci,
      ESBL- and MBL-producing bacteria. CONCLUSION: Emerging antimicrobial resistance
      calls for prompt diagnosis and aggressive empiric therapy based on the local
      sensitivity data.

PMID- 24584594
TI  - Pilot experience in senegal with peritoneal dialysis for end-stage renal disease.
AB  - ? INTRODUCTION: Peritoneal dialysis (PD) is occasionally used in western sub
      Saharan Africa to treat patients with end-stage renal disease (ESRD). The present
      study is a retrospective review of the initial six years' experience with PD for
      ESRD therapy in Senegal, a West African country with a population of over 12
      million. ? MATERIAL AND METHODS: Single-center retrospective cohort study of
      patients treated with PD between March 2004 and December 2010. Basic demographic
      data were collected on all patients. Peritonitis rates, causes of death and
      reasons for transfer to hemodialysis (HD) were determined in all patients. ?
      RESULTS: Sixty-two patients were included in the study. The median age was 47 +/-
      13 years with a male/female ratio of 1.21. Nephrosclerosis and diabetic
      nephropathy were the main causes of ESRD. The mean Charlson score was 3 +/- 1
      with a range of 2 to 7. Forty five peritonitis episodes were diagnosed in 36
      patients (58%) for a peritonitis rate of 1 episode/20 patient-months (0.60
      episodes per year). Staphylococcus aureus and Pseudomonas aeruginosa were the
      most commonly identified organisms. Touch contamination has been implicated in 26
      cases (57.7%). In 23 episodes (51%), bacterial cultures were negative. Catheter
      removal was necessary in 12 cases (26.6%) due to mechanical dysfunction, fungal
      or refractory infection. Sixteen patients died during the study. ? CONCLUSION:
      Peritoneal dialysis is a suitable therapy which may be widely used for ESRD
      treatment in western sub-Saharan Africa. A good peritonitis rate can be achieved
      despite the difficult living conditions of patients. Challenges to the
      development of PD programs include training health care providers, developing an
      infrastructure to support the program, and developing a cost structure which
      permits expansion of the PD program.

PMID- 24584593
TI  - Dialysate cytokine levels do not predict encapsulating peritoneal sclerosis.
AB  - BACKGROUND: Encapsulating peritoneal sclerosis (EPS) is a rare but devastating
      complication of long-term peritoneal dialysis (PD). There is no well-validated
      method for predicting which patients will develop the condition, although known
      risk factors include long duration of PD, high glucose exposure and lack of
      residual renal function. We have investigated whether dialysate cytokines (MCP-1
      (monocyte chemotactic protein-1), CCL18 (pulmonary and activation-regulated
      cytokine, PARC), IL-6 (interleukin-6), CCL15 (leukotactin) and angiogenin) could
      be used to predict the onset of EPS more effectively than known clinical risk
      factors. METHODS: Samples of dialysate and clinical data were prospectively
      collected from 151 patients at the West London Renal center between 2003 and
      2010. Dialysate cytokine levels were measured using the enzyme-linked
      immunoabsorbant assay (ELISA) technique. Encapsulating peritoneal sclerosis
      subsequently developed in 17 patients during a follow-up period of 27 - 113
      months. Cytokines found at higher levels in dialysate of pre-EPS patients were
      investigated as candidate predictors of EPS using logistic regression analysis.
      RESULTS: Dialysate IL-6, MCP-1 and CCL15 were significantly higher in patients
      who subsequently developed EPS; however, a logistic regression model using
      dialysate cytokines to predict EPS was no better than a model using well
      recognized clinical markers (length of time on PD and membrane transport status).
      CONCLUSIONS: Although MCP-1, IL-6 and CCL15 were found at higher levels in the
      dialysate of patients who subsequently developed EPS, dialysate levels of these
      cytokines do not improve prediction of future EPS above a model using known
      clinical risk factors.

PMID- 24584595
TI  - Mortality rates do not differ among patients prescribed various vitamin D agents.
AB  - BACKGROUND: Limited well-controlled research exists examining the impact of
      different formulations of oral vitamin D on clinical outcomes in dialysis
      patients, specifically those on peritoneal dialysis. For this retrospective
      mortality analysis, we compared mortality rates of patients on 3 of the most
      commonly prescribed vitamin D agents. METHODS: We examined 2 years (7/1/2008 to
      6/30/2010) of oral medication records of peritoneal dialysis patients from a
      large US dialysis organization. Patients were identified whose physicians
      prescribed a single form of vitamin D (calcitriol, paricalcitol, or
      doxercalciferol) for >= 90% of all patient-months. We excluded incident patients
      (< 90 days on dialysis) and patients whose physicians treated < 5 peritoneal
      dialysis patients at a dialysis facility, and we assessed mortality. RESULTS: The
      analysis inclusion criteria identified 1,707 patients. The subset in this
      analysis included 12.6% of all prevalent peritoneal dialysis patients and 11.8%
      of prevalent patient-months. Patients with physicians who predominately
      prescribed calcitriol had a lower mortality rate: 9.33 (confidence interval (CI)
      7.06, 11.60) deaths per 100 patient-years than the doxercalciferol, 12.20 (CI
      9.34, 15.06) or paricalcitol, 12.27 (CI 9.27, 15.28) groups. However, these
      differences were not statistically significant. A Cox proportional hazards model,
      adjusting for differences in age, vintage, gender, race, body mass index, and
      comorbidities also showed no significant differences. CONCLUSIONS: For this
      peritoneal dialysis population, instrumental variable analyses showed no
      significant difference in mortality in patients taking the most common oral
      vitamin D formulations (calcitriol, doxercalciferol, paricalcitol).

PMID- 24584596
TI  - Metformin in peritoneal dialysis: a pilot experience.
AB  - OBJECTIVE: In a number of patients, the antidiabetic drug metformin has been
      associated with lactic acidosis. Despite the fact that diabetes mellitus is the
      most common cause of end-stage renal disease (ESRD) and that peritoneal dialysis
      (PD) is an expanding modality of treatment, little is known about optimal
      treatment strategies in the large group of PD patients with diabetes. In patients
      with ESRD, the use of metformin has been limited because of the perceived risk of
      lactic acidosis or severe hypoglycemia. However, metformin use is likely to be
      beneficial, and PD might itself be a safeguard against the alleged complications.
      METHODS: Our study involved 35 patients with insulin-dependent type 2 diabetes
      [median age: 54 years; interquartile range (IQR): 47-59 years] on automated PD
      (APD) therapy. Patients with additional risk factors for lactic acidosis were
      excluded. Metformin was introduced at a daily dose in the range 0.5 - 1.0 g. All
      patients were monitored for glycemic control by blood sugar levels and HbA1c.
      Plasma lactic acid levels were measured weekly for 4 weeks and then monthly to
      the end of the study. Plasma and effluent metformin and plasma lactate levels
      were measured simultaneously. RESULTS: In this cohort, the median duration of
      diabetes was 18 years (IQR: 14 - 21 years), median time on PD was 31 months (IQR:
      27 - 36 months), and median HbA1c was 6.8% (IQR: 5.9% - 6.9%). At metformin
      introduction and at the end of the study, the median anion gap was 11 mmol/L
      (IQR: 9 - 16 mmol/L) and 12 mmol/L (IQR: 9 - 16 mmol/L; p > 0.05) respectively,
      median pH was 7.33 (IQR: 7.32 - 7.36) and 7.34 (IQR: 7.32 - 7.36, p > 0.05)
      respectively, and mean metformin concentration in plasma and peritoneal fluid was
      2.57 +/- 1.49 mg/L and 2.83 +/- 1.7 mg/L respectively. In the group overall, mean
      lactate was 1.39 +/- 0.61 mmol/L, and hyperlactemia (>2 mmol/L to 5 mmol/L) was
      found in 4 of 525 plasma samples (0.76%), but the patients presented no symptoms.
      None of the patients registered a plasma lactate level above 5 mmol/L. We
      observed no correlation between plasma metformin and plasma lactate (r = 0.27).
      CONCLUSIONS: Metformin may be used with caution in APD patients with insulin
      dependent type 2 diabetes. Although our study demonstrated the feasibility of
      metformin use in APD, it was not large enough to demonstrate safety; a large
      scale study is needed.

PMID- 24584597
TI  - The role of monitoring vancomycin levels in patients with peritoneal dialysis
      associated peritonitis.
AB  - BACKGROUND: There is limited available evidence regarding the role of monitoring
      serum vancomycin concentrations during treatment of peritoneal dialysis (PD)
      associated peritonitis. METHODS: A total of 150 PD patients experiencing 256
      episodes of either gram-positive or culture-negative peritonitis were included to
      investigate the relationship between measured serum vancomycin within the first
      week and clinical outcomes of cure, relapse, repeat or recurrence of peritonitis,
      catheter removal, temporary or permanent transfer to hemodialysis,
      hospitalization and death. RESULTS: Vancomycin was used as an initial empiric
      antibiotic in 54 gram-positive or culture-negative peritonitis episodes among 34
      patients. The median number of serum vancomycin level measurements in the first
      week was 3 (interquartile range; IQR 1 - 4). The mean day-2 vancomycin level,
      measured in 34 (63%) episodes, was 17.5 +/- 5.2 mg/L. Hospitalized patients were
      more likely to have serum vancomycin levels measured on day 2 and >= 3
      measurements in the first week. The peritonitis cure rates were similar between
      patients with < 3 and >= 3 measurements in the first week (77% vs 57%, p = 0.12)
      and if day-2 vancomycin levels were measured or not (68% vs 65%, p = 0.84). The
      average day-2 (18.0 +/- 5.9 vs 16.6 +/- 3.2, p = 0.5), first-week average (18.6
      +/- 5.1 vs 18.6 +/- 4.3, p = 0.9) and nadir (14.5 +/- 4.1 vs 13.6 +/- 4.2, p =
      0.5) vancomycin levels were comparable in patients who did or did not achieve
      peritonitis cure. Similar results were observed for all other clinical outcomes.
      CONCLUSION: The clinical outcomes of gram-positive and culture-negative
      peritonitis episodes are not associated with either the frequency or levels of
      serum vancomycin measurements in the first week of treatment when vancomycin is
      dosed according to International Society for Peritoneal Dialysis (ISPD)
      Guidelines.

PMID- 24584598
TI  - SAHA Suppresses Peritoneal Fibrosis in Mice.
AB  - OBJECTIVE: Long-term peritoneal dialysis causes peritoneal fibrosis in
      submesothelial areas. However, the mechanism of peritoneal fibrosis is unclear.
      Epigenetics is the mechanism to induce heritable changes without any changes in
      DNA sequences. Among epigenetic modifications, histone acetylation leads to the
      transcriptional activation of genes. Recent studies indicate that histone
      acetylation is involved in the progression of fibrosis. Therefore, we examined
      the effect of suberoylanilide hydroxamic acid (SAHA), a histone deacetylase
      inhibitor, on the progression of peritoneal fibrosis in mice. METHODS: Peritoneal
      fibrosis was induced by the injection of chlorhexidine gluconate (CG) into the
      peritoneal cavity of mice every other day for 3 weeks. SAHA, or a
      dimethylsulfoxide and saline vehicle, was administered subcutaneously every day
      from the start of the CG injections for 3 weeks. Morphologic peritoneal changes
      were assessed by Masson's trichrome staining, and fibrosis-associated factors
      were assessed by immunohistochemistry. RESULTS: In CG-injected mice, a marked
      thickening of the submesothelial compact zone was observed. In contrast, the
      administration of SAHA suppressed the progression of submesothelial thickening
      and type III collagen accumulation in CG-injected mice. The numbers of fibroblast
      specific protein-1-positive cells and alpha-smooth muscle actin alpha-positive
      cells were significantly decreased in the CG + SAHA group compared to that of the
      CG group. The level of histone acetylation was reduced in the peritoneum of the
      CG group, whereas it was increased in the CG + SAHA group. CONCLUSIONS: Our
      results indicate that SAHA can suppress peritoneal thickening and fibrosis in
      mice through up-regulation of histone acetylation. These results suggest that
      SAHA may have therapeutic potential for treating peritoneal fibrosis.

PMID- 24584599
TI  - Outbreak of Paecilomyces variotii peritonitis in peritoneal dialysis patients
      after the 2010 Chilean earthquake.

PMID- 24584600
TI  - Effect of body mass index on outcomes of peritoneal dialysis patients in India.
AB  - OBJECTIVES: We studied the effect of body mass index (BMI) at peritoneal dialysis
      (PD) initiation on patient and technique survival and on peritonitis during
      follow-up. METHODS: We followed 328 incident patients on PD (176 with diabetes;
      242 men; mean age: 52.6 +/- 12.6 years; mean BMI: 21.9 +/- 3.8 kg/m(2)) for 20.0
      +/- 14.3 months. Patients were categorized into four BMI groups: obese, >= 25
      kg/m(2); overweight, 23 - 24.9 kg/m(2); normal, 18.5 - 22.9 kg/m(2) (reference
      category); and underweight, <18.5 kg/m(2). The outcomes of interest were compared
      between the groups. RESULTS: Of the 328 patients, 47 (14.3%) were underweight,
      171 (52.1%) were normal weight, 53 (16.2%) were overweight, and 57 (17.4%) were
      obese at commencement of PD therapy. The crude hazard ratio (HR) for mortality (p
      = 0.004) and the HR adjusted for age, subjective global assessment,
      comorbidities, albumin, diabetes, and residual glomerular filtration rate (p =
      0.02) were both significantly greater in the underweight group than in the normal
      weight group. In comparison with the reference category, the HR for mortality was
      significantly greater for underweight PD patients with diabetes [2.7; 95%
      confidence interval (CI): 1.5 to 5.0; p = 0.002], but similar for all BMI
      categories of nondiabetic PD patients. Median patient survival was statistically
      inferior in underweight patients than in patients having a normal BMI. Median
      patient survival in underweight, normal, overweight, and obese patients was,
      respectively, 26 patient-months (95% CI: 20.9 to 31.0 patient-months), 50 patient
      months (95% CI: 33.6 to 66.4 patient-months), 57.7 patient-months (95% CI: 33.2
      to 82.2 patient-months), and 49 patient-months (95% CI: 18.4 to 79.6 patient
      months; p = 0.015). Death-censored technique survival was statistically similar
      in all BMI categories. In comparison with the reference category, the odds ratio
      for peritonitis occurrence was 1.8 (95% CI: 0.9 to 3.4; p = 0.086) for
      underweight patients; 1.7 (95% CI: 0.9 to 3.2; p = 0.091) for overweight
      patients; and 3.4 (95% CI: 1.8 to 6.4; p < 0.001) for obese patients.
      CONCLUSIONS: In our PD patients, mean BMI was within the normal range. The HR for
      mortality was significantly greater for underweight diabetic PD patients than for
      patients in the reference category. Death-censored technique survival was similar
      in all BMI categories. Obese patients had a greater risk of peritonitis.

PMID- 24584601
TI  - Maps of Ventricular Activation Time (VAT) Differences in Children on Peritoneal
      Dialysis - a Pilot Study.
AB  - BACKGROUND: Decrement of glomerular filtration rate leads to many serious
      complications that cause both functional and structural impairments of the other
      organs. Long-term clinical observations of children and teenagers with end-stage
      renal disease (ESRD) showed that more than one third of those patients manifested
      various cardio-vascular conditions. The aim of the study was to analyze possible
      disturbances in the heart ventricular conduction system by using a technique of
      ventricular activation time (VAT) differences in ESRF children on peritoneal
      dialysis (PD) with normal electrocardiogram (ECG) examinations. MATERIAL AND
      METHODS: The study group comprised 10 ESRD children (mean age: 13.6 +/- 2.31
      years) on peritoneal dialysis - group I. The control group (group II) consisted
      of 26 age-matched healthy children with no clinical evidence of renal or cardiac
      disease and with normal 12-lead ECG recordings. Each of the ESRD patients was
      also subjected to the standard ECG examination. In order to capture possible
      heart conduction abnormalities, body surface potential mapping (BSPM) recordings
      were performed in PD patients between the successive dwells ('on empty abdomen')
      with a HPM-7100 Fukuda Denshi system. Based on the source ECG data, the original
      technique of a VAT difference map was then applied. RESULTS: Differences between
      VAT values for the two examined groups of children, controls and ESRD patients on
      PD, were significantly pronounced in the region of the right upper anterior
      thorax, the entire left thorax and nearly in the total back. Such a pattern of
      VAT delays indicates a pathological electric transmission in the intraventricular
      conduction system of the left anterior fascicle of His bundle. CONCLUSION: 1. VAT
      maps (isochrone maps) can be useful to detect abnormal spreading and
      depolarization through the heart ventricles. 2. Map of VAT value differences
      makes it possible to identify early disturbances in the left His bundle branch in
      ESRD children treated with peritoneal dialysis regardless of normal 12-lead ECG.
      3. Further studies on a larger group of children with ESRD on PD are required to
      verify the preliminary observations presented herein.

PMID- 24584602
TI  - Clinical outcome of home hemodialysis in patients with previous peritoneal
      dialysis exposure: evaluation of the integrated home dialysis model.
AB  - BACKGROUND: Home dialysis is a cost-effective modality of renal replacement
      therapy associated with excellent outcomes. Peritoneal dialysis (PD) is the most
      common home-based modality, but technique failure remains a problem. Transfer
      from PD to home hemodialysis (HHD) allows the patient to continue with a home
      based modality, but the outcomes of patients transitioning to HHD after PD are
      largely unknown. METHODS: In a retrospective cohort study, including all
      consecutive HHD patients between January 1996 and December 2011, we evaluated the
      outcomes of patients with previous PD exposure compared to those without. The
      primary outcome was the cumulative patient and technique survival. Secondary
      outcomes included time to first hospitalization and hospitalization rate. Data
      were compared using the log-rank test and a multivariable Cox proportional
      hazards model. RESULTS: Among our cohort of 207 consecutive HHD patients, 35
      (17%) had previous exposure to PD. Median renal replacement therapy (RRT) vintage
      (12.3 years, interquartile range (IQR) 8.5 - 18.9 vs 0.9 years, IQR 0.2 - 7.5, p
      < 0.001) and Charlson comorbidity index (CCI) (4, IQR 2 - 6 vs 3, IQR 2 - 4, p =
      0.044) were higher among patients with PD exposure than those without. Despite
      the difference in vintage, cumulative patient and technique survival was similar
      in the two groups, in both unadjusted (log-rank p = 0.893) and Cox adjusted
      models (hazard ratio (HR) 1.15, 95% confidence interval (CI) 0.51 - 2.59) for
      patients with PD exposure compared to those without. The time to first
      hospitalization was shorter in patients with previous PD exposure compared to PD
      naive patients (log-rank p = 0.021). This association was preserved in the Cox
      proportional model (HR 1.65, 95% CI 1.08 - 2.54). CONCLUSION: Despite a higher
      burden of comorbidity, patients with previous PD exposure had similar cumulative
      patient and technique survival on HHD compared to those without PD exposure.
      Whenever possible, HHD should be considered in PD patients in need of a new
      dialysis modality.

PMID- 24584603
TI  - The risk factors and the impact of hernia development on technique survival in
      peritoneal dialysis patients: a population-based cohort study.
AB  - OBJECTIVES: There is a lack of consensus on the risk factors for hernia
      formation, and the impact on peritoneal dialysis (PD) survival has seldom been
      studied. METHODS: This was a population-based study and all collected data were
      retrieved from the National Health Insurance Research Database of Taiwan.
      Patients who commenced PD between January 1998 and December 2006 were screened
      for inclusion. Multiple logistic regression and Cox proportional hazards models
      were applied to estimate the predictors for hernia formation and determine the
      predictors of PD withdrawal. RESULTS: A total of 6,928 PD patients were enrolled
      and followed until December 2009, with 631 hernia events and 391 hernioplasties
      being registered in 530 patients (7.7%). The incidence rate was 0.04
      hernias/patient/year. Longer PD duration (per 1 month increase, hazard ratio (HR)
      1.019) and history of mitral valve prolapse (MVP) (HR 1.584) were independent
      risk factors for hernia formation during PD, and female gender (HR 0.617) was a
      protective factor. On the other hand, there were 4,468 PD withdrawals, with
      cumulative incidence rates of 41% at 1 year, 66% at 3 years, and 82% at 5 years.
      Independent determinants for cumulative PD withdrawal included hernia formation
      during PD (HR 1.154), age (per 1 year increase, HR 1.014), larger dialysate
      volume (per 1 liter increase, HR 0.496), female gender (HR 0.763), heart failure
      (HR 1.092), hypertension (HR 1.207), myocardial infarction (HR 1.292), chronic
      obstructive pulmonary disease (COPD) (HR 1.227), cerebrovascular accident (CVA)
      (HR 1.364), and history of MVP (HR 0.712) CONCLUSIONS: Prolonged PD duration was
      a risk factor for hernia formation, and female gender was protective. Hernia
      formation during PD therapy may increase the risk of PD withdrawal.

PMID- 24584604
TI  - Alterations of intercellular junctions in peritoneal mesothelial cells from
      patients undergoing dialysis: effect of retinoic Acid.
AB  - BACKGROUND: Dialysis patients are classified according to their peritoneal
      permeability as low transporter (LT, low solute permeability) or high transporter
      (HT, high solute permeability). Tight junction (TJ) proteins are critical to
      maintain ions, molecules and water paracellular transport through peritoneum.
      Exposure to peritoneal dialysis solutions causes damage to TJ in human peritoneal
      mesothelial cells (HPMCs). We analyzed the quantity, distribution and function of
      TJ proteins: claudin-1, -2 and -8, ZO-1 and occludin, in HPMC cultures from LT
      and HT patients. Since all-trans retinoic acid (ATRA) might modify the expression
      of TJ proteins, we studied its effect on HPMCs. METHODS: Control HPMCs were
      isolated from human omentum, while HT or LT cells were obtained from dialysis
      effluents. Cells were cultured in presence of ATRA 0, 50 or 100 nM.
      Transepithelial electrical resistance (TER) measurement, immunostaining and
      Western blot analyses were performed. RESULTS: HT exhibited lower TER than
      control and LT monolayers. Immunofluorescence for TJ was weak and discontinuous
      along the cell contour, in LT and HT. Furthermore, claudin-1, occludin and ZO-1
      expressions were decreased. In all groups, claudin-2 was localized at nuclei. We
      observed that ATRA improved TJ distribution and increased TJ expression in HT.
      This retinoid did not modify claudin-2 and -8 expressions. All-trans retinoic
      acid decreased TER in HT, but had no effect in LT. CONCLUSIONS: Tight junctions
      were altered in HPMCs from dialyzed patients. The HT monolayer has lower TER than
      LT, which might be associated with the peritoneal permeability in these patients.
      ATRA might be a therapeutic alternative to maintain mesothelial integrity, since
      it improved TJ localization and expression.

PMID- 24584605
TI  - MgCaCO3 versus CaCO3 in peritoneal dialysis patients--a cross-over pilot trial.
AB  - BACKGROUND: Despite adverse effects such as constipation, vascular calcification,
      and hypercalcemia, calcium-based salts are relatively affordable and effective
      phosphate binders that remain in widespread use in the dialysis population. We
      conducted a pilot study examining whether the use of a combined magnesium/calcium
      based binder was as effective as calcium carbonate at lowering serum phosphate
      levels in peritoneal dialysis (PD) patients. METHODS: This was a cross-over,
      investigator-masked pilot study in which prevalent PD patients received calcium
      carbonate alone (200 mg calcium per tablet) or calcium magnesium carbonate (100
      mg calcium, 85 mg magnesium per tablet). Primary outcome was serum phosphate
      level at 3 months. Analysis was as per protocol. RESULTS: Twenty patients were
      recruited, 17 completed the study. Mean starting dose was 11.35 +/- 7.04 pills
      per day of MgCaCO3 and 9.00 +/- 4.97 pills per day of CaCO3. Mean phosphate
      levels fell from 2.13 mmol/L to 2.01 mmol/L (95% confidence interval (CI): 1.76 -
      2.30, p = 0.361) in the MgCaCO3 group, and 1.81 mmol/L (95% CI: 1.56 - 2.0, p =
      0.026) in the CaCO3 alone group. Six (35%) patients taking MgCaCO3 and 9 (54%)
      taking CaCO3 alone achieved Kidney Disease Outcomes Quality Initiative (KDOQI)
      serum phosphate targets at 3 months. Diarrhea developed in 9 patients taking
      MgCaCO3 and 3 taking CaCO3. Serum magnesium exceeded 1.4 mmol/L in 5 patients
      taking MgCaCO3 while serum calcium exceeded 2.65 mmol/L in 3 patients receiving
      CaCO3. When compared to the initial dose, the prescribed dose at 3 months was
      reduced by 44% (to 6.41 tablets/day) in the MgCaCO3 group and by 8% (to 8.24
      pills per day) in the CaCO3 alone group. CONCLUSION: Compared with CaCO3 alone,
      the preparation and dose of MgCaCO3 used in this pilot study was no better at
      lowering serum phosphate levels in PD patients, and was associated with more dose
      limiting side effects.

PMID- 24584607
TI  - The association between body mass index and mortality on peritoneal dialysis: a
      prospective cohort study.
AB  - BACKGROUND: Previous studies have demonstrated that increased body mass index
      (BMI) is associated with decreased mortality in hemodialysis (HD) patients.
      However, the association between BMI and survival has not been well established
      in patients undergoing peritoneal dialysis (PD). The aim of the study was to
      determine the association between BMI and mortality in the PD population using
      the Clinical Research Center (CRC) registry for end-stage renal disease (ESRD)
      cohort in Korea. METHODS: Prevalent patients with PD were selected from the CRC
      registry for ESRD, a prospective cohort study on dialysis patients in Korea.
      Patients were categorized into four groups by quartiles of BMI. Cox regression
      analysis was used to calculate the adjusted hazard ratio (HR) of mortality with a
      BMI of quartile 2 (21.4 - 23.5 kg/m(2)) as the reference. RESULTS: A total of 900
      prevalent patients undergoing PD were included. The median follow-up period was
      24 months. The multivariate Cox proportional hazard model showed that the lowest
      quartile of BMI was associated with higher mortality (HR 3.00, 95% confidence
      interval (CI), 1.26 - 7.15). However, the higher quartiles of BMI were not
      associated with mortality compared with the reference category of BMI quartile 2
      (Quartile 3: HR 1.11, 95% CI, 0.43 - 2.85, Quartile 4: HR 1.64, 95% CI, 0.66 -
      4.06) after adjustment for clinical variables. CONCLUSIONS: Lower BMI was a
      significant risk factor for death, but increased BMI was not associated with
      mortality in Korean PD patients.

PMID- 24584606
TI  - Increased Levels of Modified Advanced Oxidation Protein Products Are Associated
      with Central and Peripheral Blood Pressure in Peritoneal Dialysis Patients.
AB  - ? BACKGROUND AND AIMS: Oxidative stress plays an important role in the
      pathogenesis of cardiovascular disease (CVD). Central blood pressure (BP) is
      thought to be more relevant than peripheral BP for the pathogenesis of CVD.
      Advanced oxidation protein products (AOPP) are markers of oxidative stress. This
      study investigated the relationship between AOPP and central BP in peritoneal
      dialysis (PD) patients. ? METHODS: In a cross-sectional study of 75 PD patients
      (67% men), we analyzed two oxidative stress markers, AOPP (modified assay, mAOPP,
      correcting for the impact of triglycerides) and pentosidine, three inflammation
      markers, interleukin-6 (IL-6), tumor necrosis factor (TNF), and high-sensitivity
      C-reactive protein (hs-CRP). All patients underwent measurement of central
      systolic blood pressure (SBP) and diastolic blood pressure (DBP) by applanation
      tonometry. ? RESULTS: Patients with mAOPP levels above the median had a higher
      central SBP and DBP than those below the median values. In univariate analysis,
      the levels of mAOPP associated with central SBP and central DBP. Multiple
      regression analysis, adjusting for age, gender, diabetes, CVD, protein-energy
      wasting (PEW), hs-CRP and extracellular water by multi-frequency bioimpedance or
      N-terminal prohormone of brain natriuretic peptide (NT-proBNP), confirmed
      independent associations between mAOPP and central SBP and central DBP
      respectively. ? CONCLUSIONS: The mAOPP level is independently associated with the
      central SBP and DBP in PD patients. This finding suggests that oxidative stress
      may be involved in the pathogenesis of hypertension or that hypertension itself
      or factors associated with hypertension such as fluid overload may have an
      additional effect on oxidative stress in PD patients.

PMID- 24584608
TI  - Comparing the Incidence of Catheter-Related Complications with Straight and
      Coiled Tenckhoff Catheters in Peritoneal Dialysis Patients-A Single-Center
      Prospective Randomized Trial.
AB  - ? OBJECTIVES: We aimed to prospectively compare the incidence of catheter-related
      complications and catheter survival for straight (SCs) and coiled (CCs) Tenckhoff
      catheters in peritoneal dialysis (PD) patients. ? METHODS: This open prospective
      randomized trial recruited 189 PD patients with end-stage renal disease from the
      department of nephrology, The First Affiliated Hospital of Sun Yat-sen University
      from 6 November 2007 to 27 August 2008. The patients were randomized to a SC (n =
      99) or a CC (n = 90) and were then followed for 2 years. All catheter placements
      were performed by two designated experienced nephrologists who used a
      standardized institutional placement protocol. The primary study outcomes were
      catheter-related complications and catheter survival at 1 and 2 years. ? RESULTS:
      We observed no significant differences in clinical and demographic
      characteristics between the groups at baseline. The overall incidence of catheter
      dysfunction was higher in the CC group than in the SC group (17.8% vs 7.1%, p =
      0.03), and most of the events occurred 4 weeks or more after the catheters were
      implanted. Catheter tip migration and omental wrapping were the most common
      causes of catheter dysfunction. Surgical catheter rescue was more common in
      patients with CCs than in patients with SCs (9 vs 3 patients respectively, p =
      0.05). No significant differences were observed in other catheter-related
      complications, including dialysate leaks, hernias, and PD-related infections
      (peritonitis, exit-site, and tunnel infections). Catheter survival rates in the
      SC and CC groups were similar at 1 year (96.7% +/- 1.9% vs 96.5% +/- 2.0%, p =
      0.98) and at 2 years (95.3% +/- 2.3% vs 92.4% +/- 3.6%, p = 0.76). ? CONCLUSIONS:
      The incidence of PD catheter-related complications is probably higher with CCs
      than with SCs. The results of our study suggest that a SC is the better option to
      reduce subsequent catheter complications.

PMID- 24584609
TI  - Removal of Different Classes of Uremic Toxins in APD vs CAPD: A Randomized Cross
      Over Study.
AB  - ? AIM: In this study, we investigated, and this for the different classes of
      uremic toxins, whether increasing dialysate volume by shifting from continuous
      ambulatory peritoneal dialysis (CAPD) to higher volume automated peritoneal
      dialysis (APD) increases total solute clearance. ? METHODS: Patients on
      peritoneal dialysis were randomized in a cross-over design to one 24-hour session
      of first a CAPD regimen (3*2 L of Physioneal 1.36% and 1*2 L of icodextrin) or
      APD (consisting of 5 cycles of 2 L Physioneal 1.36 and 1 cycle of 2 L Extraneal),
      and the other week the alternate regime, each patient serving as his/her own
      control. Dialysate, blood and urine samples were collected and frozen for later
      batch analysis of concentrations of urea, creatinine, phosphorus, uric acid,
      hippuric acid, 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid, indoxyl
      sulfate, indole acetic acid, and p-cresyl sulfate. For the protein-bound solutes,
      total and free fractions were determined. Total, peritoneal and renal clearance
      (K) and mass removal (MR) of each solute were calculated, using validated models.
      ? RESULTS: In 15 patients (11 male, 3 diabetics, 56 +/- 16 years, 8 on CAPD, time
      on peritoneal dialysis 12 +/- 14 months, and residual renal function of 9.9 +/-
      5.4 mL/min) dialysate over plasma ratio for creatinine (D/Pcrea) was 0.62 +/-
      0.10. Drained volume and obtained ultrafiltration were higher with APD vs CAPD
      (13.3 +/- 0.5 L vs 8.5 +/- 0.7 L and 1.3 +/- 0.5 L vs 0.5 +/- 0.7 L), whereas
      urine output was lower (1.0 +/- 0.5 L vs 1.4 +/- 0.6 L). Total clearance and MR
      tended to be higher for CAPD vs APD for all small and water soluble solutes, but
      mainly because of higher renal contribution, with no difference in the peritoneal
      contribution. For the protein-bound solutes, no differences in clearance or mass
      removal were observed. ? CONCLUSION: Although the drained dialysate volume nearly
      doubled, APD did not result in better peritoneal clearance or solute removal vs
      classic CAPD. APD resulted in better ultrafiltration, but at the expense of
      residual urinary output and clearance.

PMID- 24584611
TI  - Outcome of acute kidney injury in Sudanese children - an experience from a sub
      Saharan African unit.
AB  - ? BACKGROUND: Acute Kidney Injury (AKI) is an important cause of morbidity and
      mortality in developing countries. Although continuous renal replacement therapy
      is gaining more popularity worldwide, peritoneal dialysis (PD) in children
      remains an appropriate therapy for AKI in children for all age groups including
      neonates. ? METHODOLOGY: We retrospectively reviewed all children who have been
      admitted with AKI at the pediatric nephrology unit, Soba University Hospital,
      Khartoum, during the period from January 2005 to December 2011. ? RESULTS: Over 7
      years we recorded 659 children of whom 362 (54.9%) were male. The spectrum of age
      was variable with the majority being neonates, 178 (27.1%). The average patient
      admission rate was 94 patients per year, with an estimated incidence of 9.8
      patients/million population/year. Common causes of AKI were sepsis 202 (30.8%),
      acute glomerulonephritis 75 (11.5%) and obstructive uropathy due to stones 56
      (8.5%). The most common dialysis modality used was PD, 343 (52.4%), and
      peritonitis was reported in 53 (15.4%) patients. Recovery from AKI was achieved
      in 450 (68.9%) children, 37 (5.7%) went into chronic kidney disease (CKD), 33
      (5.1%) referred to the pediatric surgery and 194 (29.7%) died. ? CONCLUSION: In
      the setting of developing countries where AKI is a common cause of morbidity and
      mortality, reasonably equipped renal units with adequately trained medical staff
      may save many lives. International funding programs for communicable diseases and
      charity organizations should include AKI management in their programs. Acute PD
      remains the treatment modality of choice for AKI in developing countries.

PMID- 24584610
TI  - Predicting the Peritoneal Absorption of Icodextrin in Rats and Humans Including
      the Effect of alpha-Amylase Activity in Dialysate.
AB  - BACKGROUND: Contrary to ultrafiltration, the three-pore model predictions of
      icodextrin absorption from the peritoneal cavity have not yet been reported
      likely, in part, due to difficulties in estimating the degradation of glucose
      polymer chains by alpha-amylase activity in dialysate. We incorporated this
      degradation process in a modified three-pore model of peritoneal transport to
      predict ultrafiltration and icodextrin absorption simultaneously in rats and
      humans. METHODS: Separate three-pore models were constructed for humans and rats.
      The model for humans was adapted from PD Adequest 2.0 including a clearance term
      out of the peritoneal cavity to account for the absorption of large molecules to
      the peritoneal tissues, and considering patients who routinely used icodextrin by
      establishing steady-state plasma concentrations. The model for rats employed a
      standard three-pore model in which human kinetic parameters were scaled for a rat
      based on differences in body weight. Both models described the icodextrin
      molecular weight (MW) distribution as five distinct MW fractions. First order
      kinetics was applied using degradation rate constants obtained from previous in
      vitro measurements using gel permeation chromatography. Ultrafiltration and
      absorption were predicted during a 4-hour exchange in rats, and 9 and 14-hour
      exchanges in humans with slow to fast transport characteristics with and without
      the effect of amylase activity. RESULTS: In rats, the icodextrin MW profile
      shifted towards the low MW fractions due to complete disappearance of the MW
      fractions greater than 27.5 kDa. Including the effect of amylase activity (60
      U/L) resulted in 21.1% increase in ultrafiltration (UF) (7.6 mL vs 6.0 mL) and
      7.1% increase in icodextrin absorption (CHO) (62.5% with vs 58.1%). In humans,
      the shift in MW profile was less pronounced. The fast transport (H) patient
      absorbed more icodextrin than the slow transport (L) patient during both 14-hour
      (H: 47.9% vs L: 40.2%) and 9-hour (H: 37.4% vs L: 31.7%) exchanges. While the UF
      was higher during the longer exchange, it varied modestly among the patient types
      (14-hour range: 460 - 509 mL vs 9-hour range: 382 - 389 mL). When averaged over
      all patients, the increases in UF and CHO during the 14-hour exchange due to
      amylase activity (7 U/L) were 15% and 1.5%, respectively. CONCLUSION: The
      icodextrin absorption values predicted by the model agreed with those measured in
      rats and humans to accurately show the increased absorption in rats. Also, the
      model confirmed the previous suggestions by predicting an increase in UF specific
      to amylase activity in dialysate, likely due to the added osmolality by the small
      molecules generated as a result of the degradation process. As expected, this
      increase was more pronounced in rats than in humans because of higher dialysate
      concentrations of amylase in rats.

PMID- 24584612
TI  - Anthropometrics Identify Wasting in Patients Undergoing Surgery for Encapsulating
      Peritoneal Sclerosis.
AB  - ? INTRODUCTION: Encapsulating peritoneal sclerosis (EPS) is a serious
      complication of peritoneal dialysis in which gastrointestinal (GI) symptoms
      reduce appetite and dietary intake. Adequate nutrition is important, especially
      if surgery is required. Although the incidence of EPS is low, the present report
      is able to detail preoperative nutrition status and treatment in a large cohort
      of patients from a national EPS referral center. ? METHODS: Of 51 patients
      admitted to this EPS specialist center hospital for their first peritonectomy in
      the study period, 50 had a preoperative dietetic assessment, and 49 underwent
      upper-arm anthropometry. ? RESULTS: Mean body mass index (BMI) was 20.6 kg/m(2).
      Mean weight loss was 14% of body weight in the preceding 6 months, with 35 of 50
      patients losing more than 10%. On anthropometry, 25 of 49 patients were below the
      5th percentile for mid-arm circumference (MAC), 17 of 49 were below for triceps
      skinfold thickness (TSF), and 21 of 49 were below for mid-arm muscle
      circumference (MAMC). Mean handgrip strength (HGS) was 60% of normal, with 43 of
      49 patients being below 85% of normal. Appetite was poor in 21 of 50 patients,
      and 37 of 50 had upper and 40 of 50 had lower GI symptoms. By subjective global
      assessment, 27 of 51 patients were graded as severely malnourished, and 5 of 51,
      as well-nourished. Mean serum albumin was 28 g/L and did not correlate with BMI,
      MAC, TSF, MAMC, or HGS. In most patients, C-reactive protein was elevated (mean:
      111 mg/L). Preoperative parenteral nutrition was given to 46 of 51 patients for a
      mean of 21 days. ? DISCUSSION: Our findings demonstrate the poor nutrition status
      of patients admitted for EPS surgical intervention. Anthropometrics reveal
      depleted fat and lean body mass in EPS patients, which might be a result of
      anorexia and inflammation, and the reason that albumin was not an accurate marker
      of nutrition. Poor nutrition status is likely to negatively affect outcome in
      this patient group. ? CONCLUSIONS: Early recognition of GI symptoms may herald a
      diagnosis of EPS. Optimization of preoperative nutrition status with intensive
      nutrition support is needed.

PMID- 24584613
TI  - Peginesatide to Manage Anemia in Chronic Kidney Disease Patients on Peritoneal
      Dialysis.
AB  - ? BACKGROUND: Peginesatide is a novel, synthetic, peptide-based pegylated
      erythropoiesis-stimulating agent that is designed specifically to stimulate the
      erythropoietin receptor. The purpose of the present study was to assess, for the
      first time, the efficacy and safety of peginesatide in chronic kidney disease
      (CKD) patients receiving peritoneal dialysis (PD) and previously on epoetin
      treatment. ? METHODS: In this open-label multicenter study, 59 PD patients with
      CKD were converted from epoetin (alfa or beta) to once-monthly peginesatide.
      Doses were titrated to maintain hemoglobin levels between 10 g/dL and 12 g/dL
      during the 25 weeks of the study. The primary endpoint was change from baseline
      in mean hemoglobin values during the evaluation period (weeks 20 - 25). ?
      RESULTS: The mean hemoglobin value during the evaluation period was 11.3 +/- 1.07
      g/dL, and the mean change from baseline was 0.10 +/- 1.15 g/dL (95% confidence
      limits: -0.24, 0.44 g/dL). During the evaluation period, most patients maintained
      hemoglobin levels between 10 g/dL and 12 g/dL (63.0%) and within +/-1.0 g/dL of
      baseline (60.9%). The median weekly epoetin dose at baseline was 96.0 U/kg, and
      the median starting peginesatide dose was 0.047 mg/kg. Forty-three patients
      (72.9%) completed the study. Six patients (10.2%) received red blood cell
      transfusions. The observed adverse event profile was consistent with underlying
      conditions in the PD patient population. The most common adverse event was
      peritonitis (20.3%), a complication commonly associated with PD. Four deaths
      occurred during the study (2 related to septic shock, and 1 each to myocardial
      ischemia and myasthenia gravis). ? CONCLUSIONS: In this study, once-monthly
      peginesatide maintained hemoglobin levels in PD patients after conversion from
      epoetin.

PMID- 24584614
TI  - Can EPS development be avoided with early interventions? The potential role of
      tamoxifen--a single-center study.
AB  - BACKGROUND: Encapsulating peritoneal sclerosis (EPS) is a severe complication of
      peritoneal dialysis (PD). Identification of patients at high risk for EPS ("EPS
      prone") and delivery of appropriate interventions might prevent its development.
      Our aim was to evaluate the clinical characteristics and outcomes of all EPS and
      EPS-prone patients diagnosed at our PD unit. METHODS: For a 30-year period
      representing our entire PD experience, we retrospectively identified all patients
      with EPS (diagnosed according to International Society for Peritoneal Dialysis
      criteria) and all patients defined as EPS-prone because they met at least 2
      established criteria (severe peritonitis, PD vintage greater than 3 years, severe
      hemoperitoneum, overexposure to glucose, and acquired ultrafiltration failure).
      RESULTS: Of 679 PD patients, we identified 20 with EPS, for an overall prevalence
      of 2.9%. Mean age at diagnosis was 50.2 +/- 16.4 years, with a median PD time of
      77.96 months (range: 44.36 - 102.7 months) and a median follow-up of 30.91 months
      (range: 4.6 - 68.75 months). Of patients with EPS, 10 (50%) received tamoxifen,
      10 (50%) received parenteral nutrition, and 2 (10%) underwent adhesiolysis, with
      25% mortality related to EPS. Another 14 patients were identified as EPS-prone.
      Median follow-up was 54.05 months (range: 11.9 - 87.04 months). All received
      tamoxifen, and 5 (36%) received corticosteroids; none progressed to full EPS. We
      observed no differences in baseline data between the groups, but the group with
      EPS had been on PD longer (84 +/- 53 months vs 39 +/- 20 months, p = 0.002) and
      had a higher cumulative number of days of peritoneal inflammation from
      peritonitis (17.2 +/- 11.1 days vs 9.8 +/- 7.9 days, p = 0.015). Overall
      mortality was similar in the groups. The incidence of EPS declined during our
      three decades of experience (5.6%, 3.9%, and 0.3%). CONCLUSIONS: Being a serious,
      life-threatening complication of PD, EPS requires high suspicion to allow for
      prompt diagnosis and treatment. Early detection of EPS-prone states and delivery
      of appropriate intervention might prevent EPS development. Tamoxifen seems to be
      a key strategy in prevention, but caution should be used in interpreting our
      results. Additional randomized controlled studies are needed.

PMID- 24584615
TI  - Case Report of Cryptococcus Albidus Peritonitis in a Peritoneal Dialysis Patient
      and a Review of the Literature.
AB  - Cryptococcus albidus is a saprophytic yeast linked to just 26 reports of human
      infection in the world literature. Here, we report the first case of C. albidus
      peritonitis, in a patient with end-stage renal disease and hepatitis C-associated
      cirrhosis who is on peritoneal dialysis. The patient was treated successfully
      with a week-long course of amphotericin B. Non-neoformans cryptococcal infections
      present a clinical challenge, because they are difficult to diagnose and lack
      established guidelines for treatment. We present a review of the literature on C.
      albidus infections and their treatment. 

PMID- 24584617
TI  - Development and Testing of Self-Management Scale for PD Patients.
AB  - OBJECTIVES: To develop and evaluate the self-management scale for peritoneal
      dialysis (PD) patients. METHODS: The item pool was formulated based on literature
      reviews and in-depth interviews. An initial scale containing five factors and 44
      items was constructed through two rounds of Delphi expert consultation and a
      preliminary test. A total of 313 PD patients from the Jiangsu-Zhejiang-Shanghai
      area were surveyed to test the reliability and validity of the scale. RESULTS:
      Five factors, namely solution bag replacement, troubleshooting during operation,
      diet management, complication monitoring, emotion management and return to social
      life, were extracted by exploratory factor analysis: the 28 items could explain
      64.567% of the total variance; the content validity index was 0.963; the
      Cronbach's alpha coefficient and split-half coefficient were 0.926 and 0.960
      respectively; and test-retest reliability was 0.937. CONCLUSION: The scale has
      been proved to be a reliable and valid tool which allows PD nurses to evaluate
      the self-management ability of PD patients. The evaluation outcomes can serve as
      a basis for individualized nursing plans and interventions so as to provide
      highly effective nursing care.

PMID- 24584616
TI  - Low-Polydispersity Glucose Polymers as Osmotic Agents for Peritoneal Dialysis.
AB  - ? BACKGROUND: Peritoneal dialysis (PD) solutions containing icodextrin as the
      osmotic agent have advantages during long dwells. The glucose polymers that
      constitute icodextrin are a heterogeneous mix of molecules with a polydispersity
      [ratio of weight-average to number-average molecular weight (Mw/Mn)] of
      approximately 2.6. The present study evaluates whether modifications in the
      polydispersity and concentration of glucose polymers can improve ultrafiltration
      (UF) without an associated increase in carbohydrate absorption (CA). ? METHODS:
      Computer simulations using a three-pore model of peritoneal transport during a
      long dwell in PD patients predict that, in general, compared with 7.5%
      icodextrin, glucose polymers with a Mw greater than or equal to 7.5 kDa, a
      polydispersity less than 2.6, and concentrations greater than 7% could achieve
      higher UF without higher CA. Based on the simulations, we hypothesized that,
      compared with 7.5% icodextrin, glucose polymers with a Mw of 18 - 19 kDa and a
      polydispersity of 2.0 at 11% concentration could achieve higher UF without a
      higher CA. We tested this hypothesis in experimental studies using 8-hour dwells
      in New Zealand White rabbits. In those studies, UF was measured by complete fluid
      collection, and CA was measured by subtracting the total carbohydrate in the
      collected fluid from the carbohydrate initially infused. ? RESULTS: The UF was
      higher with 11% 19 kDa glucose polymer than with 7.5% icodextrin (mean +/-
      standard deviation: 89 +/- 31 mL vs 49 +/- 15 mL; p = 0.004) without higher CA
      (5.2 +/- 0.9 g vs 5.0 +/- 0.9 g, p = 0.7). Similar results were seen with the 11%
      18 kDa glucose polymer, which, compared with 7.5% icodextrin, resulted in higher
      UF (mean +/- standard deviation: 96 +/- 18 mL vs 66 +/- 17 mL; p < 0.001) without
      higher CA (4.8 +/- 0.7 g vs 5.2 +/- 0.6 g, p = 0.2). ? CONCLUSIONS: The findings
      demonstrate that, compared with 7.5% icodextrin solution, long-dwell PD solutions
      containing 11% glucose polymers with a Mw of 18-19 kDa and a polydispersity of
      2.0 can provide higher UF without higher CA.

PMID- 24584618
TI  - Prognostic value of serum von Willebrand factor, but not soluble ICAM and VCAM,
      for mortality and cardiovascular events is independent of residual renal function
      in peritoneal dialysis patients.
AB  - OBJECTIVE: We explored associations between markers of endothelial dysfunction
      and outcome events, and whether those associations were independent of residual
      renal function (RRF) in patients on peritoneal dialysis. METHODS: The study
      enrolled 261 incident patients and 68 healthy control subjects who were followed
      till death, censoring, or study end. Demographics, biochemistry, markers of
      inflammation (C-reactive protein) and endothelial dysfunction [soluble
      intercellular adhesion molecule 1 (sICAM), soluble vascular adhesion molecule 1
      (sVCAM), and von Willebrand factor (vWf)] were examined at baseline. Outcome
      events included all-cause death and fatal and nonfatal cardiovascular (CV)
      events. RESULTS: Mean levels of vWf, sICAM, and sVCAM were significantly higher
      in patients than in healthy control subjects. Levels of sICAM and sVCAM, but not
      vWf, were significantly correlated with RRF. Levels of sICAM and vWf both
      predicted all-cause mortality and fatal and nonfatal CV events after adjustment
      for recognizable CV risk factors. The association between sICAM and outcome
      events disappeared after further adjustment for RRF. However, RRF did not change
      the predictive role of vWf for outcome events. Compared with the lowest vWf
      quartile (6.6% - 73.9%), the highest vWf quartile (240.9% - 1161%) predicted the
      highest risk for fatal and nonfatal CV events (adjusted hazard ratio: 2.05; 95%
      confidence interval: 1.15 to 3.64; p = 0.014). We observed no associations
      between sVCAM and RRF, or sVCAM and any outcome event. CONCLUSIONS: The
      prognostic value of vWf, but not sICAM, is independent of RRF in predicting
      mortality and CV events.

PMID- 24584620
TI  - 32 years' experience of peritoneal dialysis-related peritonitis in a university
      hospital.
AB  - BACKGROUND: Peritonitis in peritoneal dialysis (PD) patients can lead to
      technique failure and contributes to infection-related mortality. Peritonitis
      prevention and optimization of treatment are therefore important in the care for
      PD patients. In the present study, we analyzed the incidence of peritonitis,
      causative pathogens, clinical outcomes, and trends in relation to three major
      treatment changes that occurred from 1979 onward: use of a disconnect system
      since 1988, daily mupirocin at the exit-site since 2001, and exclusive use of
      biocompatible dialysis solutions since 2004. METHODS: In this analysis of
      prospectively collected data, we included peritonitis episodes from the start of
      PD at our center in August 1979 to July 2010. Incident PD patients were allocated
      to one of four groups: Group 1 - 182 patients experiencing 148 first peritonitis
      episodes between 1979 and 1987, before the introduction of the disconnect system;
      Group 2 - 352 patients experiencing 239 first episodes of peritonitis between
      1988 and 2000, before implementation of daily mupirocin application at the
      catheter exit-site; Group 3 - 79 patients experiencing 50 first peritonitis
      episodes between 2001 and 2003, before the switch to biocompatible solutions; and
      Group 4-118 patients experiencing 91 first peritonitis episodes after 2004.
      Cephradine was used as initial antibiotic treatment. RESULTS: In 32 years, 731
      adult patients started PD, and 2234 episodes of peritonitis in total were
      diagnosed and treated. Of those episodes, 88% were cured with medical treatment
      only, and 10% resulted in catheter removal. In 3% of the episodes, the patient
      died during peritonitis. Median time to a first peritonitis episode increased
      from 40 days for group 1 to 150 for group 2, 269 for group 3, and 274 for group
      4. The overall peritonitis rate and the gram-positive and gram-negative
      peritonitis rates showed a time-trend of decline. However, the duration of
      antibiotic treatment increased over time, with groups 3 and 4 having the longest
      duration of treatment, accompanied by a higher percentage of antibiotic switch.
      Increased resistance to cephradine was found for coagulase-negative
      Staphylococcus. CONCLUSIONS: Peritonitis rates declined significantly over the
      years because of several changes in PD treatment. However, the need to change the
      initial antibiotic increased because of diminished antibiotic susceptibility
      rates over time. Nevertheless, the cure rate was high and remained stable during
      the entire period analyzed, and the death rate remained low. Consequently,
      peritonitis is a manageable complication of PD that cannot be considered a
      contraindication to this mode of renal replacement therapy.

PMID- 24584619
TI  - Intraperitoneal fluid overestimates hydration status assessment by bioimpedance
      spectroscopy.
AB  - BACKGROUND: Bioimpedance spectroscopy (BIS) is a valuable tool to assess
      nutrition and volume status in peritoneal dialysis (PD) patients. However, data
      about the influence of intraperitoneal fluid on body composition measures are
      conflicting, and there is no clear consensus about whether the abdomen should be
      drained before the procedure. We designed a comparison study to detect the
      influence of intra-abdominal fluid on BIS results. METHODS: We performed 73 pairs
      of BIS measurements in 34 stable PD patients, first with the peritoneum filled
      with a 1.36% glucose dialysate solution and then after the solution was drained.
      Patients stayed in the supine position for 10 minutes before the BIS procedure,
      and the electrodes were not moved between measures. Clinical and demographic data
      were collected, as were analytic parameters of nutrition and volume status.
      RESULTS: Fluid overload is overestimated when BIS is performed with a full
      abdomen (1.82 +/- 1.73 L vs 1.64 +/- 1.68 L, p = 0.043). We also found a spurious
      overestimation in extracellular water (16.40 +/- 3.21 L vs 16.24 +/- 3.16 L, p <
      0.001) and in relative overhydration (8.29% +/- 6.96% vs 7.14% +/- 6.79%, p =
      0.017). No differences in intracellular water or parameters of nutrition were
      found. We observed negative correlations for the extracellular water
      overestimation with age (r = -0.245, p = 0.037), serum B-type natriuretic peptide
      (r = -0.366, p = 0.036), body mass index (r = -0.248, p = 0.035), and lean tissue
      index (r = -0.427, p = 0.001). The difference in extracellular water correlated
      only with body mass index (r = -0.259, p = 0.039). We also found that, assessed
      at 50 KHz, whole-body impedance (-4.52 +/- 8.37, p = 0.001) and phase angle (
      0.08 +/- 0.23 degrees, p = 0.002) were both lower when BIS was performed in
      patients with a full abdomen. CONCLUSIONS: Fluid overload is overestimated by BIS
      when performed in patients with dialysate in the peritoneum. The observed
      differences are greater in younger, more poorly nourished, or less overhydrated
      patients. If more precise results are required, we suggest that the abdomen be
      drained before BIS is performed.

PMID- 24584622
TI  - Best practices consensus protocol for peritoneal dialysis catheter placement by
      interventional radiologists.
AB  - Peritoneal dialysis (PD) catheters can be placed by interventional radiologists,
      an approach that might offer scheduling efficiencies, cost-effectiveness, and a
      minimally invasive procedure. In the United States, changes in the dialysis
      reimbursement structure by the Centers for Medicare and Medicaid Services are
      expected to result in the increased use of PD, a less costly dialysis modality
      that offers patients the opportunity to receive dialysis in the home setting and
      to have more independence for travel and work schedules, and that preserves
      vascular access for future dialysis options. Placement of PD catheters by
      interventional radiologists might therefore be increasingly requested by
      nephrology practices, given that recent publications have demonstrated the
      favorable impact on PD practices of an interventional radiology PD placement
      capability. Earlier reports of interventional radiology PD catheter placement
      came from single-center practices with smaller reported experiences. The need for
      a larger consensus document that attempts to establish best demonstrated
      practices for radiologists is evident. The radiologists submitting this consensus
      document represent a combined experience of more than 1000 PD catheter
      placements. The authors submit these consensus-proposed best demonstrated
      practices for placement of PD catheters by interventional radiologists under
      ultrasonographic and fluoroscopic guidance. This technique might allow for
      expeditious placement of permanent PD catheters in late-referred patients with
      end-stage renal disease, thus facilitating urgent-start PD and avoiding the need
      for temporary vascular access catheters. 

PMID- 24584621
TI  - Oxidative DNA damage and mortality in hemodialysis and peritoneal dialysis
      patients.
AB  - BACKGROUND AND AIMS: Increased oxidative stress in dialysis patients is thought
      to contribute to increased mortality; however, confirmatory data are scarce. We
      analyzed the serum concentration of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a
      marker of oxidative stress, in relation to mortality in hemodialysis (HD) and
      peritoneal dialysis (PD) patients. METHODS: Serum 8-OHdG, interleukin 6 (IL-6),
      other biochemical markers, Davies comorbidity score, and protein-energy wasting
      (PEW) were assessed in 303 prevalent patients treated with HD (n = 220; age: 63
      +/- 14 years) or PD (n = 83; age: 64 +/- 14 years). Mortality was assessed after
      a median follow-up of 31 months. RESULTS: The median (25th - 75th percentile)
      concentration of 8-OHdG was higher in HD than in PD patients: 1.3 ng/mL (0.9 -
      1.8 ng/mL) versus 0.5 ng/mL (0.4 - 0.6 ng/mL), p < 0.001. The HD modality
      (standard beta = 0.57, p < 0.001) and dialysis vintage (standard beta = 0.12, p =
      0.02) were independent predictors of serum 8-OHdG in a multivariable linear
      regression model including age, sex, body mass index, dialysis modality (HD or
      PD), preceding time on dialysis (dialysis vintage), PEW, comorbidity score, IL-6,
      and use of angiotensin converting-enzyme inhibitors or angiotensin II receptor
      blockers or statins. During follow-up, 107 patients died. In multivariable Cox
      regression models including all 303 patients and adjusted for age, sex, body mass
      index, dialysis modality, dialysis vintage, and comorbidity score, 8-OHdG was
      significantly associated with all-cause mortality (adjusted hazard ratio: 1.40;
      95% confidence limits: 1.05, 1.87 for 1 standard deviation increase of 8-OHdG).
      In subgroup analyses according to dialysis modality, 8-OHdG was associated with
      mortality in HD patients but not in PD patients. CONCLUSIONS: Oxidative stress as
      assessed by 8-OHdG is an independent predictor of all-cause mortality in dialysis
      patients. This association was seen in HD patients, but no such association could
      be demonstrated for PD patients.

PMID- 24584631
TI  - Carbon-carbon bond cleavage in activation of the prodrug nabumetone.
AB  - Carbon-carbon bond cleavage reactions are catalyzed by, among others, lanosterol
      14-demethylase (CYP51), cholesterol side-chain cleavage enzyme (CYP11), sterol
      17beta-lyase (CYP17), and aromatase (CYP19). Because of the high substrate
      specificities of these enzymes and the complex nature of their substrates, these
      reactions have been difficult to characterize. A CYP1A2-catalyzed carbon-carbon
      bond cleavage reaction is required for conversion of the prodrug nabumetone to
      its active form, 6-methoxy-2-naphthylacetic acid (6-MNA). Despite worldwide use
      of nabumetone as an anti-inflammatory agent, the mechanism of its carbon-carbon
      bond cleavage reaction remains obscure. With the help of authentic synthetic
      standards, we report here that the reaction involves 3-hydroxylation, carbon
      carbon cleavage to the aldehyde, and oxidation of the aldehyde to the acid, all
      catalyzed by CYP1A2 or, less effectively, by other P450 enzymes. The data
      indicate that the carbon-carbon bond cleavage is mediated by the ferric peroxo
      anion rather than the ferryl species in the P450 catalytic cycle. CYP1A2 also
      catalyzes O-demethylation and alcohol to ketone transformations of nabumetone and
      its analogs. 

PMID- 24584632
TI  - Genetic influence on capillary oxygen saturation: a twin study.
AB  - BACKGROUND: While heritability has been shown for daytime sleepiness, the
      heritability of daytime capillary oxygen saturation (SpO(2)) has not been
      described in detail. Our aim was to estimate the role of genes and environmental
      factors--both shared and unshared--in the variation of daytime SpO(2). METHODS: A
      total of 193 adult healthy twin pairs (138 monozygotic, 55 dizygotic) were
      recruited in Hungary and in the United States [age = 43.6 +/- 15.6 years (mean +/
      SD)]. SpO(2) was measured by pulse oximetry. Univariate quantitative genetic
      modeling was performed to decompose the phenotypic variance of the considered
      parameter into heritability (A), shared (C), and unshared (E) environmental
      effects. RESULTS: SpO(2) twin correlation in monozygotic twins was stronger than
      in dizygotic twins (0.30 and -0.15, respectively, p < 0.05). Age-, sex-, country
      , and body mass index-adjusted genetic effects accounted for 26 % (95 % CI 10, 45
      %) of the variance of SpO(2), and the unshared environmental component explained
      the remaining 74 % (95 % CI 59, 89 %). No shared environmental influence on
      SpO(2) was detected. The heritability of SpO(2) was not different between smokers
      and nonsmokers. CONCLUSION: In summary, individual differences in daytime SpO(2)
      are explained by genetic and unshared environmental effects. The strong unshared
      environmental influence highlights the role of prevention of known environmental
      risk factors.

PMID- 24584633
TI  - Contact heat-evoked potentials as a useful means in patients with Guillain-Barre
      syndrome.
AB  - Few objective methods have been utilized to identify the small myelinated fiber
      impairment causing neuropathic pain in Guillain-Barre syndrome (GBS). In this
      study, contact heat-evoked potentials (CHEPs) were applied to study the
      nociceptive pathway in GBS. Sixty GBS patients and fifty healthy controls were
      enrolled. The 60 GBS patients were divided into two subgroups presenting with or
      without subjective lower limb paresthesia (21/39). CHEPs were recorded at Cz and
      Pz with a peak thermal stimuli of 47  degrees C applied to the skin of the leg
      above the internal malleolus (AIM) and of the waist at the anterior superior
      iliac spine (ASIS) level. The N2 latency and N2-P2 amplitude of CHEPs were
      compared. When the skin of the leg AIM was stimulated, the N2 latency was
      significantly postponed (425.23 +/- 28.66 vs. 402.30 +/- 19.48 ms, P < 0.05) and
      the N2-P2 amplitude significantly decreased in GBS patients as compared to
      controls (32.71 +/- 7.49 vs. 42.77 +/- 8.71 MUV, P < 0.05). Slower nerve
      conduction velocity was observed in GBS patients (11.84 +/- 1.45 vs. 13.28 +/-
      0.66 ms, P < 0.05). However, no differences in N2 latency or N2-P2 amplitude were
      detected between the two subgroups of GBS patients with or without subjective
      lower limb paresthesia (P all >0.05). Moreover, there were no differences in N2
      latency and N2-P2 amplitude among different groups when the waist was stimulated
      at the ASIS level. Our study suggested that CHEPs could be utilized as an
      objective and non-invasive tool to detect small myelinated fiber damage in GBS
      patients, especially for those without subjective paresthesia.

PMID- 24584634
TI  - Effects of catalpol on ATPase and amino acids in gerbils with cerebral
      ischemia/reperfusion injury.
AB  - This study aimed to investigate the effects of catalpol on ATPase and amino acids
      in gerbils following cerebral ischemia/reperfusion (CI/R) injury. Gerbil model of
      CI/R was prepared by bilateral common carotid occlusion for 10 min followed by 6
      h of reperfusion. Catalpol (5, 10 or 20 mg/kg per day) was injected
      intraperitoneally for 3 days before the carotid occlusion. Stroke index was
      measured during the reperfusion. ATPase activity, glutamate (Glu) and aspartate
      contents in brain tissue homogenate were examined. The results showed that
      catalpol significantly improved the stroke index compared with sham group (P <
      0.05 or P < 0.01). Catalpol markedly increased the activities of Na(+)-K(+)
      ATPase and Ca(2+)-ATPase (P < 0.05 or P < 0.01), and significantly decreased the
      content of Glu in brain tissue (P < 0.05 or P < 0.01). These data suggest that
      the efficacy of catalpol pretreatment on CI/R injury is associated with the
      enhancement of ATPase activity and the inhibition of excitatory amino acid
      toxicity.

PMID- 24584635
TI  - Twelve-year monitoring of a patient with megalencephalic leukoencephalopathy with
      subcortical cysts.
AB  - Megalencephalic leukoencephalopathy (MLC) with subcortical cysts is an infantile
      onset inherited disease of the brain white matter with a defect in brain ion and
      water homoeostasis, which leads to an abnormal brain volume regulation. Clinical
      features of the disease can be variable, but patients typically show early-onset
      macrocephaly, motor abnormalities, seizures, and almost constant late-onset mild
      mental deterioration. Brain magnetic resonance imaging (MRI) reveals diffusely
      abnormal and mildly swollen white matter as well as subcortical cysts in the
      anterior temporal and frontoparietal regions. We describe here clinical findings
      and volumetric MRI and (1)H-MR spectroscopic imaging ((1)H-MRSI) data of a 12
      year follow-up on a patient with MLC. The patient had only slight clinical
      worsening during the long follow-up. Volumetric findings showed substantially
      unchanged cystic volumes and mild brain atrophy rate. In addition, there was no
      over time increase in the volume of white matter hypointense lesions seen on
      FLAIR images at baseline, but the degree of hypointensity of these white matter
      voxels increased over 12 years. Longitudinal (1)H-MRSI examination showed long
      term undetectable metabolite signals in the white matter, whereas the metabolic
      pattern of gray matter voxels remained unchanged over time. Results show that, in
      MLC, the chronic brain white matter changes resulting from the brain ion, and
      water homeostasis can be monitored by quantitative MRI modalities. This might be
      important for assessing treatment effects.

PMID- 24584636
TI  - Cerebrotendinous xanthomatosis: recurrence of the CYP27A1 mutation p.Arg479Cys in
      Sardinia.

PMID- 24584637
TI  - A new isothermal nucleic acid detection strategy mediated by a double-nicked
      beacon.
AB  - A new isothermal and cascade signal amplification method for sensitive nucleic
      acid detection was developed, which is ultra-simple because it only depends on
      one double-nicked beacon. 

PMID- 24584638
TI  - Ectopic prolactin-producing pituitary adenoma in a benign ovarian cystic
      teratoma.
AB  - We report the presence of pituitary tissue in a benign ovarian cystic teratoma
      removed surgically from a 43-year-old woman. The pituitary consisted of non
      tumorous neurohypophysis and adenohypophysis containing mainly prolactin (PRL)
      immunopositive cells (80 % of cells) and a small PRL-producing adenoma. The
      ultrastructure of the tumor cells differed significantly from PRL cells in the
      non-tumorous and adenomatous intrasellar pituitary. It appears that cells
      differing in ultrastructure from intrasellar pituitary PRL cells can also produce
      PRL.

PMID- 24584639
TI  - Chemical, microbiological, and spatial characteristics and impacts of
      contaminants from urban catchments: CABRRES project.

PMID- 24584640
TI  - Influence of the inlet air in efficiency of photocatalytic devices for
      mineralization of VOCs in air-conditioning installations.
AB  - Nowadays, a large proportion of photocatalytic oxidation (PCO) devices are being
      implemented in heating, ventilation and air-conditioning systems. However, no
      systematic studies have been carried out regarding the influence of inlet air
      preconditioning. To analyse the impact of the inlet air-conditions into
      photocatalytic efficiency, a simulated air-conditioning duct with flowing gas
      through inside was designed. Isobutylene was chosen as the target VOCs. The
      concentration in the gas phase was monitored using a photoionization detector.
      The influence of flow rate, relative humidity and temperature on the VOC removal
      efficiency was analysed. Experimental results were presented in terms of gas
      removal efficiency (eta) and clean air delivery rate (CADR) and analysed on a
      kinetic basis. From them, the weight of each parameter in the global process has
      been determined, from bigger to smaller contribution, flow>>temperature>relative
      humidity. Also, the relevance of the inlet air conditions has been illustrated in
      a model room in order to determinate the time necessary to obtain a threshold
      value accomplishing with enough air quality and the energy consumption of the
      device. Additionally, the photocatalytic decontamination has been assimilated to
      the "air exchange rate", a parameter commonly used in indoor air quality studies.
      The results show that preconditioning of air can improve the efficiency of
      photocatalytic devices and bring important energy savings. 

PMID- 24584641
TI  - Characterization of SDS-degrading Delftia acidovorans and in situ monitoring of
      its temporal succession in SDS-contaminated surface waters.
AB  - Incomplete removal of sodium dodecyl sulfate (SDS) in wastewater treatment plants
      may result in SDS residues escaping and finding their way into receiving water
      bodies like rivers, lakes, and sea. Introduction of effective microorganisms into
      the aerobic treatment facilities can reduce unpleasant by-products and SDS
      residues. Selecting effective microorganisms for SDS treatment is a big
      challenge. Current study reports the isolation, identification, and in situ
      monitoring of an effective SDS-degrading isolate from detergent-polluted river
      waters. Screening was carried out by the conventional enrichment culture
      technique and the isolate was tentatively identified by using fatty acid methyl
      ester and 16S ribosomal RNA (rRNA) sequence analyses. Fatty acids produced by the
      isolate investigated were assumed as typical for the genus Comamonas. 16S rRNA
      sequence analysis also confirmed that the isolate had 95% homology with Delftia
      acidovorans known as Comamonas or Pseudomonas acidovorans previously. D.
      acidovorans exhibited optimum growth at SDS concentration of 1 g l(-1) but
      tolerated up to 10 g l(-1) SDS. 87% of 1.0 g l(-1) pure SDS was degraded after 11
      days of incubation. The temporal succession of D. acidovorans in detergent
      polluted river water was also monitored in situ by using Comamonas-specific
      fluorescein-labeled Cte probe. Being able to degrade SDS and populate in SDS
      polluted surface waters, D. acidovorans isolates seem to be very helpful in
      elimination of SDS.

PMID- 24584642
TI  - The challenges of reducing greenhouse gas emissions and air pollution through
      energy sources: evidence from a panel of developed countries.
AB  - The objective of the study is to investigate the long-run relationship between
      climatic factors (i.e., greenhouse gas emissions, agricultural methane emissions,
      and industrial nitrous oxide emission), air pollution (i.e., carbon dioxide
      emissions), and energy sources (i.e., nuclear energy; oil, gas, and coal energy;
      and fossil fuel energy) in the panel of 35 developed countries (including EU-15,
      new EU member states, G-7, and other countries) over a period of 1975-2012. In
      order to achieve this objective, the present study uses sophisticated panel
      econometric techniques including panel cointegration, panel fully modified OLS
      (FMOLS), and dynamic OLS (DOLS). The results show that there is a long-run
      relationship between the variables. Nuclear energy reduces greenhouse gases and
      carbon emissions; however, the other emissions, i.e., agricultural methane
      emissions and industrial nitrous oxide, are still to increase during the study
      period. Electricity production from oil, gas, and coal sources increases the
      greenhouse gases and carbon emissions; however, the intensity to increase
      emissions is far less than the intensity to increase emissions through fossil
      fuel. Policies that reduce emissions of greenhouse gases can simultaneously alter
      emissions of conventional pollutants that have deleterious effects on human
      health and the environment. 

PMID- 24584643
TI  - Inoculation with arbuscular mycorrhizal fungi and addition of composted olive
      mill waste enhance plant establishment and soil properties in the regeneration of
      a heavy metal-polluted environment.
AB  - A greenhouse experiment was carried out in order to investigate the effects of
      arbuscular mycorrhizal (AM) fungi inoculation and the use of composted olive
      waste (COW) in the establishment of Tetraclinis articulata and soil properties in
      a heavy metal-polluted soil. The treatments assayed were as follows: AM + 0% COW,
      AM + 1% COW, and AM + 3% COW. The higher doses of COW in combination with AM
      fungi increased shoot and root biomass production of T. articulata by 96 and 60%,
      respectively. These treatments trended to improve the soil properties evaluated,
      highlighting the C compounds and N as well as the microbiological activities. In
      relation to the metal translocation in T. articulata, doses of COW applied
      decreased the Cr, Ni, and Pb contents in shoot, as well as Cr and As in root,
      although the most of them reached low levels and far from phytotoxic. The COW
      amendment aided Glomus mosseae-inoculated T. articulata plants to thrive in
      contaminated soil, mainly through an improvement in both nutrients uptake, mainly
      P and soil microbial function. In addition, the combined use of AM fungi plus COW
      could be a feasible strategy to be incorporated in phytoremediation programs
      because it promotes soil properties, a better performance of plants for
      supporting the stress in heavy metal-contaminated soils derived from the mining
      process, and also can be a good way for olive-mill waste disposal.

PMID- 24584644
TI  - Substitution pattern reverses the fluorescence response of coumarin glycoligands
      upon coordination with silver (I).
AB  - Development of sugar-based fluorescence (FL) chemo-probes is of much interest
      since sugars are biocompatible, water-soluble and structurally rigid natural
      starting materials. We report here that fluorescent glycoligands with two
      triazolyl coumarin moieties installed onto the different positions of an
      identical glucosyl nucleus exert completely reversed optical response to a metal
      ion. C3,4-, C2,3- and C4,6-di-substituted coumarin glucosides synthesized by a
      click reaction similarly showed a selective FL variation in the presence of
      silver (I) among a range of metal cations in an aqueous solution. However, the
      variation was determined to be converse: the FL of the C3,4-ligand was quenched
      whereas that of the C2,3/C4,6-ligand tangibly enhanced. FL and NMR titrations
      suggested that this divergence was due to the distinct complexation modes of the
      conformationally constrained ligands with the ion. The optimal motifs of the
      ligand-ion complexation were predicted by a computational simulation. Finally,
      the C2,3-ligand was determined to be of low cytotoxicity and applicable in the FL
      imaging of silver ions internalized by live cells. 

PMID- 24584645
TI  - The appearance of the pre-Achilles fat pad after endoscopic calcaneoplasty.
AB  - PURPOSE: To evaluate whether the imaging features of the retrocalcaneal recess
      normalize on a conventional radiograph after surgery for retrocalcaneal bursitis
      and evaluate whether it can be reused if complaints reoccur. METHODS: Patients
      who underwent an endoscopic calcaneoplasty at least 2 years before were eligible
      for inclusion. A lateral conventional radiograph of the surgically treated
      hindfoot was made to assess the retrocalcaneal recess and pre-Achilles fat pad;
      images were analysed, clinical complaints were registered and evaluated.
      Radiographs were evaluated by two experienced observers (one orthopaedic surgeon
      one musculoskeletal specialized radiologist), these scored the images either as
      "normal" (no obliteration of retrocalcaneal recess and pre-Achilles fat) or as
      "abnormal". RESULTS: Thirty patients (34 heels: 28 asymptomatic and 6 recurrent
      complaints) were included in this study. Observer one rated 12 images as "normal"
      (2 symptomatic heels and 10 asymptomatic), 22 "abnormal". Observer two rated 9
      "normal" (1 symptomatic heels and 8 asymptomatic), 25 "abnormal". No correlation
      between the radiographic appearance and complaints (n.s.) was found. Cohen's
      kappa for interobserver agreement was low (0.11 n.s.). CONCLUSION: The appearance
      of the retrocalcaneal recess on a lateral radiograph cannot be used as a reliable
      diagnostic criterion for retrocalcaneal bursitis in patients who previously
      underwent endoscopic calcaneoplasty. This study clinical relevance is based upon
      the conclusion that a lateral radiograph cannot be used after endoscopic
      calcaneoplasty, whereas previous work reported the diagnostic value of a lateral
      radiograph for retrocalcaneal bursitis prior to surgery. LEVEL OF EVIDENCE: III.

PMID- 24584646
TI  - High reliability in digital planning of medial opening wedge high tibial
      osteotomy, using Miniaci's method.
AB  - PURPOSE: Pre-operative planning is essential in high tibial osteotomy (HTO).
      Miniaci's method employs Mikulicz's weight-bearing line and is advantageous
      because the point of mechanical loading is related to the known degenerative
      condition of the knee. Miniaci's geometrical method has been modified for an
      opening wedge and described for use with a digital picture archiving and
      communications system viewer. Reliability for this method was hypothesised to be
      equivalent to published reliability for landmark-based commercial software and
      independent of observer experience. METHODS: Twenty-four patients awaiting HTO
      had standardised long-leg radiographs. Mikulicz's weight-bearing line was
      projected through the lateral compartment of the knee at Fujisawa's point. The
      correction angle was generated at the hinge point subtending the current and
      proposed ankle centres. The opening wedge was plotted to measure an opening
      distance. Observations were recorded twice by three observers. Agreement was
      reported as intraclass correlation coefficients with 95 % confidence intervals.
      RESULTS: Intra-rater agreement was excellent for the correction angle (0.965
      0.985) and opening distance (0.928-0.980). If no set hinge point was used, then
      the inter-rater reliability was 0.986 for the correction angle and 0.984 for the
      opening distance. There was no discernible pattern demonstrating improved
      reliability from the experienced observer. CONCLUSIONS: Reliability is comparable
      to commercially based landmark software and independent of observer experience.
      This makes such geometrical pre-operative planning accessible to surgeons who
      perform HTO with insufficient frequency to justify the investment in commercial
      software. LEVEL OF EVIDENCE: Diagnostic study, Level II.

PMID- 24584647
TI  - Women outperform men in ultradistance swimming: the Manhattan Island Marathon
      Swim from 1983 to 2013.
AB  - PURPOSE: Recent studies suggested that women's and men's ultraswim performances
      may be similar for distances of ~ 35 km. The current study investigated both the
      gender difference and the age of peak ultraswim performance between 1983 and 203
      at the 46-km Manhattan Island Marathon Swim with water temperatures < 20 degrees
      C. METHODS: Changes in race times and gender difference in 551 male and 237
      female finishers were investigated using linear-, nonlinear, and hierarchical
      multilevel-regression analyses. RESULTS: The top 19 race times ever were
      significantly (P < .0001) lower for women (371 +/- 11 min) than for men (424 +/-
      9 min). Race times of the annual 3 fastest women and men did not differ between
      genders and remained stable across years. The age of the annual 3 fastest
      swimmers increased from 28 +/- 4 y (1983) to 38 +/- 6 y (2013; r2 = .06, P = .03)
      in women and from 23 +/- 4 y (1984) to 42 +/- 8 y (2013; r2 = .19, P < .0001 )in
      men. CONCLUSION: The best women were ~12 - 14% faster than the men in a 46-km
      open-water ultradistance race with temperatures < 20 degrees C. The maturity of
      ultradistance swimmers has changed during the last decades, with the fastest
      swimmers becoming older across the years.

PMID- 24584659
TI  - Molecular cloning and characterization of the lipopolysaccharide and beta-1,3
      glucan binding protein from oriental river prawn, Macrobrachium nipponense.
AB  - The lipopolysaccharide and beta-1,3-glucan binding protein (LGBP), one of the
      pattern recognition proteins, plays an important role in the innate immune
      response of invertebrates. A 1,506 bp full-length cDNA of a LGBP gene was cloned
      and characterized from the oriental river prawn Macrobrachium nipponense (named
      as MnLGBP). Analysis of the nucleotide sequence revealed that the cDNA clone has
      an open reading frame of 1,119 bp, encoding a protein of 372 amino acids
      including a 21-aa signal peptide. The calculated molecular mass of the mature
      protein (351 aa) was 39.9 kDa with an estimated pI of 4.63. The MnLGBP sequence
      contains: (1) two putative integrin-binding motifs, (2) a glucanase motif, (3)
      two putative N-glycosylation sites, (4) one protein kinase C phosphorylation
      site, and (5) a putative recognition motif for beta-1,3-linkage of
      polysaccharides. Sequence comparison based on the deduced amino acid sequence of
      MnLGBP showed varied identity of 89, 76 and 74% with those of Macrobrachium
      rosenbergii LGBP, Marsupenaeus japonicus beta-1,3-glucan binding proteins, and
      Fenneropenaeus chinensis LGBP, respectively. Quantitative RT-PCR results showed
      that MnLGBP was expressed in nerve, intestine, muscle, gill, heart, haemocytes
      and at the highest level in hepatopancreas. After challenge with the pathogen,
      Aeromonas hydrophila and Vibrio parahaemolyticus, the expression of MnLGBP mRNA
      was significantly upregulated in the hepatopancreas compared to the control
      group. At the same time, the mRNA level of MnproPO increased dramatically at 48 h
      after injection of bacteria. These data should be helpful to better understand
      the function of MnLGBP in the prawn immune system.

PMID- 24584660
TI  - The effect of NF-kappaB antisense oligonucleotide on transdifferentiation of
      fibroblast in lung tissue of mice injured by bleomycin.
AB  - To investigate the influence of NF-kappaB antisense oligonucleotide on
      transdifferentiation of fibroblast in the pathological process of bleomycin
      induced pulmonary fibrosis in mice. 6 h before molding of C57BL/6 model of
      pulmonary fibrosis in mice, NF-kappaB antisense oligonucleotide was injected from
      caudal vein. Then the lung tissue was collected for primary culture as well as
      model group and control group. Cultured cells were used for immunocytochemical
      staining of p65, IkappaB-alpha and alpha-SMA proteins as well as in situ
      hybridization staining of p65 and IkappaB-alpha. Then image analysis was carried
      out. The expressions of all the indicators were expressed as mean optical
      density. Compared with the control group, the expressions of p65 protein, IkappaB
      alpha protein and alpha-SMA protein of model group were increased, as well as the
      expressions of p65 mRNA and IkappaB-alpha mRNA (P < 0.05). Compared with model
      group, the expressions of all indicators of intervention group were decreased (P
      < 0.05). P65 protein and p65 mRNA were positively correlated with the expression
      of alpha-SMA protein respectively. p65 protein and p65 mRNA were positively
      correlated with the expressions of IkappaB-alpha protein and IkappaB-alpha mRNA
      respectively. NF-kappaB antisense oligonucleotide can inhibit the
      transdifferentiation of fibroblast towards myofibroblast in the pathological
      process of bleomycin-induced pulmonary fibrosis in mice.

PMID- 24584661
TI  - The impact of antiandrogen 2-hydroxyflutamide on the expression of steroidogenic
      enzymes in cultured porcine ovarian follicles.
AB  - We used our model system for agonism and antagonism of the androgen receptor
      (AR), in which the porcine ovarian follicles were exposed on the excessive
      concentration of an AR agonist- testosterone (T) or an AR antagonist- 2
      hydroxyflutamide (2-Hf) to: (1) analyze the spatiotemporal expression of ovarian
      3beta-hydroxysteroid dehydrogenase (3beta-HSD), cytochrome P450 17alpha
      hydroxylase/c17,20-lyase (P450c17) and cytochrome P450 aromatase (P450arom); (2)
      to determine the contribution of AR-mediated action during steroidogenesis and
      (3) to establish some correlations between the onset and expression pattern of
      the investigated proteins. Whole follicles (6-8 mm in diameter) isolated from
      mature porcine ovaries have been incubated (for 24 h) in an organ culture system
      in the presence of T (10(-7 )M), 2-Hf (1.7 * 10(-4) M) or both T and 2
      hydroxyflutamide (T+2-Hf, at the same concentrations as when added separately).
      Thereafter, sections obtained from cultured follicles were processed for main
      steroidogenic enzymes detection by immunohistochemistry. Moreover, expression of
      their mRNA and protein was determined by real-time PCR and Western blot analysis.
      Progesterone, androgens and estradiol concentrations in the culture media were
      measured by radioimmunoassays (RIA). Our results demonstrated that 2-Hf can
      influence the steroidogenic activity of porcine follicles in vitro through the
      blockade of AR. It was shown that follicular 2-Hf treatment brought about
      dramatic decline in the production of the investigated steroids. What is more the
      addition of 2-Hf separately caused a negative effect on 3beta-HSD and P450c17
      mRNA and protein expression by ovarian follicles, while it was without effect on
      P450arom mRNA level. Quite opposite effect was observed in case of the
      simultaneous addition of 2-Hf and T. It caused high increase, in both P450arom
      mRNA and its protein. What was interesting, addition T+2-Hf evoked 3beta-HSD and
      P450c17 increase on mRNA level, but decreased their protein expression. This was
      against our expectations but the reason for that finding remains undiscovered,
      intriguing and worth reporting. These results suggest that alike, steroidogenic
      enzymes activity and their expression is associated with the presence of
      androgens and AR in the porcine ovary.

PMID- 24584663
TI  - Estimation of adult patient doses for common diagnostic X-ray examinations in Wad
      madani, Sudan: derivation of local diagnostic reference levels.
AB  - The objectives of this study were to estimate patient dose in some common
      diagnostic X-ray examinations. Radiation doses were estimated for 307 patients in
      six public hospitals comprising 7 X-ray units in Wad-madani, Sudan. Entrance
      surface air kerma (ESAK) was estimated in a three step protocol: First, X-ray
      unit output Y(d) was measured at a distance, d for different peak tube voltages
      and tube loadings (mAs). Next, incident air kerma (Ki) was calculated from Y(d)
      using inverse square law combined with patient exposure factors. ESAK was
      calculated from Ki using backscatter factor, B. Mean ESAK values are comparable
      to those reported in other countries and are below reference dose levels. The
      estimated mean ESAK values are: 0.3, 2.2, 2.2, 2.9, 2.8, 3.1, and 7.5 mGy for
      chest PA, Skull AP/PA, Skull LAT, Abdomen, Pelvis AP, Lumbar Spine AP and Lumbar
      Spine LAT examinations, respectively. The results are used for dose optimization,
      and to propose local diagnostic reference levels.

PMID- 24584662
TI  - Identification two novel nacrein-like proteins involved in the shell formation of
      the Pacific oyster Crassostrea gigas.
AB  - Nacrein-like proteins have carbonic anhydrase (CA)-like domains, but their coding
      regions are flanked by inserted repeat sequence, such as Gly-X-Asn. Reportedly,
      nacrein-like proteins show the highest similarity to human carbonic anhydrase
      1(alpha-CA1), possess CA catalytic functions, and play a key role in shell
      biomineralization. In the present study, two novel nacrein-like proteins were
      firstly identified from the shell-forming mantle of the Pacific oyster
      Crassostrea gigas. With numerous analyses, it was identified and characterized
      that both the nacrein-like proteins F1 and F2 were secreted and most closely
      related to the nacrein-like protein of California mussel Mytilus californianus
      via phylogenetic analysis. RT-PCR analysis showed that the nacrein-like proteins
      F1 and F2 were expressed in multiple tissues and the expression levels remarkably
      rose after entering the spat stage, which were basically consistent with the
      increase of calcite fractions in the total shell volume. Surprisingly, the Gly-X
      Asn repeat domain, which is distinctive in most nacrein-like proteins, was absent
      in the two newly identified nacrein-like proteins in C. gigas and replaced with a
      series of acidic amino acids (D/E). Regardless, nacrein-like proteins in mollusks
      seem to be vital to the deposition of calcium carbonate and likely perform
      diverse functions. 

PMID- 24584665
TI  - Increased incidence of adenoidectomy and tonsillectomy in children with renal
      transplantation.
AB  - BACKGROUND: Previous studies have found that pediatric solid organ transplant
      recipients suffer from adenotonsillar hyperplasia. However, as this condition is
      also common in normal children, it remains unclear whether the incidence is truly
      increased. The aim of this study was to compare the incidences of surgery on the
      adenoids and tonsils of normal children with those receiving renal transplants
      and to define risk factors in the transplant population. METHODS: Data on 49
      consecutive children from a single renal transplant unit were compared to data
      from a large governmental survey of healthy German children (KiGGS). For analysis
      of 'survival without operation', controls were matched for gender, region and
      immigration status (n = 8,650), as well as for age to compare incidence rates (n
      = 637). RESULTS: The age-matched solid organ transplant recipients had a higher
      incidence of adenoidectomies [2.3-fold, [95 % confidence interval (CI) for
      relative risk 1.6-3.3) and a higher incidence of tonsillectomies/tonsillotomies
      (3.5-fold, 95 % CI 2.1-5.7). The normal peak of adenoidectomies was delayed by 2
      years in the pre-school group, and transplanted teenagers showed an extra peak
      for both operations. Boys and those transplanted at a younger age were
      significantly more likely to need adenoidectomies. Ciclosporin levels, Epstein
      Barr virus and cytomegalovirus infections did not influence the incidence of
      operations. CONCLUSION: Children receiving renal transplants are at markedly
      increased risk of adenotonsillar hyperplasia requiring surgery, especially males
      and young recipients.

PMID- 24584666
TI  - Anisotropic Janus Si nanopillar arrays as a microfluidic one-way valve for gas
      liquid separation.
AB  - In this paper, we demonstrate a facile strategy for the fabrication of a one-way
      valve for microfluidic (MF) systems. The micro-valve was fabricated by embedding
      arrays of Janus Si elliptical pillars (Si-EPAs) with anisotropic wettability into
      a MF channel fabricated in poly(dimethylsiloxane) (PDMS). Two sides of the Janus
      pillar are functionalized with molecules with distinct surface energies. The
      ability of the Janus pillar array to act as a valve was proved by investigating
      the flow behaviour of water in a T-shaped microchannel at different flow rates
      and pressures. In addition, the one-way valve was used to achieve gas-liquid
      separation. We believe that the Janus Si-EPAs modified by specific surface
      functionalization provide a new strategy to control the flow and motion of fluids
      in MF channels. 

PMID- 24584664
TI  - Genetic causes of proteinuria and nephrotic syndrome: impact on podocyte
      pathobiology.
AB  - In the past 20 years, multiple genetic mutations have been identified in patients
      with congenital nephrotic syndrome (CNS) and both familial and sporadic focal
      segmental glomerulosclerosis (FSGS). Characterization of the genetic basis of CNS
      and FSGS has led to the recognition of the importance of podocyte injury to the
      development of glomerulosclerosis. Genetic mutations induce injury due to effects
      on the podocyte's structure, actin cytoskeleton, calcium signaling, and lysosomal
      and mitochondrial function. Transgenic animal studies have contributed to our
      understanding of podocyte pathobiology. Podocyte endoplasmic reticulum stress
      response, cell polarity, and autophagy play a role in maintenance of podocyte
      health. Further investigations related to the effects of genetic mutations on
      podocytes may identify new pathways for targeting therapeutics for nephrotic
      syndrome. 

PMID- 24584667
TI  - Differential expression of apoptosis-related factors induces the age-related
      apoptosis of the gracilis muscle in humans.
AB  - In the normal aging process, apoptosis has been implicated as a mechanism
      responsible for the loss of muscle cells and plays an important role in age
      related muscle loss. Several signaling pathways involved in skeletal muscle
      apoptosis are currently under intense investigation, particularly the caspase
      independent pathway. This study investigated the age-related apoptotic changes
      occurring in the gracilis muscle in humans between 10 and 50 years of age. For
      this purpose, muscle samples were divided into 5 groups (n=8). Terminal
      deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining and
      immunofluorescence detection were performed to determine the number of apoptotic
      muscle cells in each group. In addition, the expression levels of apoptosis
      related factors, such as Bcl-2, Bax, apoptosis-inducing factor (AIF), caspase-3
      and calpain-1 were determined by RT-PCR and western blot analysis. TUNEL assay
      revealed a significant increase in gracilis muscle apoptosis with aging. The
      activity of caspase-3 in the gracilis muscle tended to change with age, although
      the changes were not significant, while the increase in DNA nuclei in muscle from
      50 years of age (5.419+/-0.97) was associated with an increase in the expression
      of AIF, as observed both at protein (10-30%) and mRNA level (10-60%) in gracilis
      tissues. Taken together, our results demonstrated that the relative Bcl-2
      expression decreased with aging, while Bax expression was upregulated compared to
      10-year-olds. In addition, a double-labeling experiment with TUNEL staining and
      immunofluorescence revealed the co-localization of nuclear AIF-positive and TUNEL
      labeled cells. This study suggests that apoptosis in gracilis skeletal muscle in
      the elderly is partly mediated through the expression of Bcl-2/Bax and the
      degradation of AIF.

PMID- 24584668
TI  - From design of bio-based biocomposite electrospun scaffolds to osteogenic
      differentiation of human mesenchymal stromal cells.
AB  - Electrospinning coupled with electrospraying provides a straightforward and
      robust route toward promising electrospun biocomposite scaffolds for bone tissue
      engineering. In this comparative investigation, four types of poly(3
      hydroxybutyrate) (PHB)-based nanofibrous scaffolds were produced by
      electrospinning a PHB solution, a PHB/gelatin (GEL) mixture or a PHB/GEL/nHAs
      (hydroxyapatite nanoparticles) mixed solution, and by electrospinning a PHB/GEL
      solution and electrospraying a nHA dispersion simultaneously. SEM and TEM
      analyses demonstrated that the electrospun nHA-blended framework contained a
      majority of nHAs trapped within the constitutive fibers, whereas the
      electrospinning-electrospraying combination afforded fibers with a rough surface
      largely covered by the bioceramic. Structural and morphological characterizations
      were completed by FTIR, mercury intrusion porosimetry, and contact angle
      measurements. Furthermore, an in vitro investigation of human mesenchymal stromal
      cell (hMSC) adhesion and proliferation properties showed a faster cell
      development on gelatin-containing scaffolds. More interestingly, a long-term
      investigation of hMSC osteoblastic differentiation over 21 days indicate that
      hMSCs seeded onto the nHA-sprayed scaffold developed a significantly higher level
      of alkaline phosphatase activity, as well as a higher matrix biomineralization
      rate through the staining of the generated calcium deposits: the fiber surface
      deposition of nHAs by electrospraying enabled their direct exposure to hMSCs for
      an efficient transmission of the bioceramic osteoinductive and osteoconductive
      properties, producing a suitable biocomposite scaffold for bone tissue
      regeneration.

PMID- 24584669
TI  - Design and characterization of a chitosan physical gel promoting wound healing in
      mice.
AB  - In this study, a sterile and biocompatible chitosan (CHI) gel for wound healing
      applications was formulated. CHI powder was treated in autoclave (ttCHI) to
      prepare sterile formulations. The heat treatment modified the CHI molecular
      weight, as evidenced by GPC analysis, and its physical-chemical features.
      Differential scanning calorimetry studies indicated that the macromolecules,
      before and after thermal treatment, differ in the strength of water-polymer
      interaction leading to different viscoelastic and flow properties. Thermally
      treated CHI exhibited the following effects: (i) increased the proliferation and
      migration of human foreskin foetal fibroblasts at 24 h; (ii) accelerated wound
      healing (measured as area of lesion) at 3 and 10 days in an in vivo model of
      pressure ulcers. These effects were linked to the increase of the hydroxyproline
      and haemoglobin content as well as Wnt protein expression. Moreover, we found a
      reduction of myeloperoxidase activity and TNF-alpha mRNA expression. These
      observations suggest the potential of this novel CHI gel in wound healing and
      other therapeutic applications.

PMID- 24584670
TI  - Prostaglandin E2 upregulates beta1 integrin expression via the E prostanoid 1
      receptor/nuclear factor kappa-light-chain-enhancer of activated B cells pathway
      in non-small-cell lung cancer cells.
AB  - The prostaglandin E2 (PGE2) E prostanoid (EP)1 receptor shown to be associated
      with lung cancer cell invasion. However, the mechanism of EP1 receptor-mediated
      cell migration remains to be elucidated. beta1 integrin is an essential regulator
      of the tumorigenic properties of non-small-cell lung carcinoma (NSCLC) cells. To
      date, little is known regarding the association between the EP1 receptor and
      beta1 integrin expression. The present study investigated the effect of EP1
      receptor activation on beta1 integrin expression and cell migration in NSCLC
      cells. A total of 34 patients with clinical diagnosis of NSCLC and 10 patients
      with benign disease were recruited for the present study. The expression levels
      of the EP1 receptor and beta1 integrin expression were studied in resected lung
      tissue using immunohistochemistry. A statistical analysis was performed using
      Stata se12.0 software. The effects of PGE2, EP1 agonist 17-phenyl trinor-PGE2 (17
      PT-PGE2) and the nuclear factor kappa-B (NF-kappaB) inhibitor on beta1 integrin
      expression were investigated on A549 cells. The expression of beta1 integrin and
      the phosphorylation of NF-kappaB-p65 Ser536 was investigated by western blot
      analysis. Cell migration was assessed by a transwell assay. The results
      demonstrated that beta1 integrin and EP1 receptor expression exhibited a positive
      correlation of evident significance in the 44 samples. The in vitro migration
      assay revealed that cell migration was increased by 30% when the cells were
      treated with 5 uM 17-PT-PGE2 and that the pre-treatment of beta1 integrin
      monoclonal antibody inhibited 17-PT-PGE2-mediated cell migration completely. PGE2
      and 17-PT-PGE2 treatment increased beta1 integrin expression. RNA interference
      against the EP1 receptor blocked the PGE2-mediated beta1 integrin expression in
      A549 cells. Treatment with 17-PT-PGE2 induced NF-kappaB activation, and the
      selective NF-kappaB inhibitor pyrrolidinedithiocarbamate inhibited 17-PT-PGE2
      mediated beta1 integrin expression. In conclusion, the present study indicated
      that the PGE2 EP1 receptor regulates beta1 integrin expression and cell migration
      in NSCLC cells by activating the NF-kappaB signaling pathway. Targeting the
      PGE2/EP1/beta1 integrin signaling pathway may aid in the development of new
      therapeutic strategies for the prevention and treatment of this type of cancer.

PMID- 24584671
TI  - Shaping a lateralized brain: asymmetrical light experience modulates access to
      visual interhemispheric information in pigeons.
AB  - Cerebral asymmetries result from hemispheric specialization and interhemispheric
      communication pattern that develop in close gene-environment interactions. To
      gain a deeper understanding of developmental and functional interrelations, we
      investigated interhemispheric information exchange in pigeons, which possess a
      lateralized visual system that develops in response to asymmetrical ontogenetic
      light stimulation. We monocularly trained pigeons with or without embryonic light
      experience in color discriminations whereby they learned another pair of colors
      with each eye. Thereby, information from the ipsilateral eye had to be
      transferred. Monocular tests confronting the animals with trained and transferred
      color pairs demonstrated that embryonic light stimulation modulates the balance
      of asymmetrical handling of transfer information. Stronger embryonic stimulation
      of the left hemisphere significantly enhanced access to interhemispheric visual
      information, thereby reversing the right-hemispheric advantage that develops in
      the absence of embryonic light experience. These data support the critical role
      of environmental factors in molding a functionally lateralized brain. 

PMID- 24584679
TI  - Vitamin D receptor expression is associated with improved overall survival in
      human glioblastoma multiforme.
AB  - Vitamin D and its analogs have been shown to display anti-proliferative effects
      in a wide variety of cancer types including glioblastoma multiforme (GBM). These
      anticancer effects are mediated by its active metabolite, 1alpha, 25
      dihydroxyvitamin D3 (calcitriol) acting mainly through vitamin D receptor (VDR)
      signaling. In addition to its involvement in calcitriol action, VDR has also been
      demonstrated to be useful as a prognostic factor for some types of cancer.
      However, to our knowledge, there are no studies evaluating the expression of VDR
      protein and its association with outcome in gliomas. Therefore, we investigated
      VDR expression by using immunohistochemical analysis in human glioma tissue
      microarrays, and analyzed the association between VDR expression and clinico
      pathological parameters. We further investigated the effects of genetic and
      pharmacologic modulation of VDR on survival and migration of glioma cell lines.
      Our data demonstrate that VDR is increased in tumor tissues when compared with
      VDR in non-malignant brains, and that VDR expression is associated with an
      improved outcome in patients with GBM. We also show that both genetic and
      pharmacologic modulation of VDR modulates GBM cellular migration and survival and
      that VDR is necessary for calcitriol-mediated effects on migration. Altogether
      these results provide some limited evidence supporting a role for VDR in glioma
      progression. 

PMID- 24584680
TI  - 5-HT7 receptors are involved in neurogenic dural vasodilatation in an
      experimental model of migraine.
AB  - Neurogenic dural vasodilation has been demonstrated to play an important role in
      migraine. 5-HT(7) receptors have been found on trigeminal nerve endings and
      middle meningeal arteries and demonstrated involved in the dilatation of
      meningeal arteries. The aim of the present study was to demonstrate whether 5
      HT(7) receptors are involved in neurogenic dural vasodilation in migraine. The
      neurogenic dural vasodilation model of migraine was used in this study.
      Unilateral electrical stimulation of dura mater was performed in anesthetized
      male Sprague-Dawley rats. Animals were pretreated with selective 5-HT(7) receptor
      agonist AS19, 5-HT(7) receptor antagonist SB269970, 5-HT1B/1D receptor agonist
      sumatriptan, or vehicles. Blood flow of the middle meningeal artery (MMA) was
      measured by a laser Doppler flowmetry. AS19 significantly increased the basal and
      stimulated blood flows of the middle meningeal artery following electrical
      stimulation of dura mater, and its effect was dose dependent at the early stage.
      SB269970 and sumatriptan significantly reduced the basal and stimulated blood
      flows of middle meningeal artery. The present study demonstrates for the first
      time that 5-HT(7) receptors are involved in neurogenic dural vasodilation evoked
      by electrical stimulation of dura mater and maybe of relevance in the
      pathophysiology and treatment of migraine.

PMID- 24584681
TI  - From esophagus to rectum: a comprehensive review of alimentary tract perforations
      at computed tomography.
AB  - Gastrointestinal (GI) tract perforation is a life-threatening condition that can
      occur at any site along the alimentary tract. Early perforation detection and
      intervention significantly improves patient outcome. With a high sensitivity for
      pneumoperitoneum, computed tomography (CT) is widely accepted as the diagnostic
      modality of choice when a perforated hollow viscus is suspected. While confirming
      the presence of a perforation is critical, clinical management and surgical
      technique also depend on localizing the perforation site. CT is accurate in
      detecting the site of perforation, with segmental bowel wall thickening, focal
      bowel wall defect, or bubbles of extraluminal gas concentrated in close proximity
      to the bowel wall shown to be the most specific findings. In this article, we
      will present the causes for perforation at each site throughout the GI tract and
      review the patterns that can lead to prospective diagnosis and perforation site
      localization utilizing CT images of surgically proven cases.

PMID- 24584682
TI  - Prevalence and factors associated with polypharmacy in older people with cancer.
AB  - PURPOSE: Polypharmacy has been associated with drug-drug interactions, adverse
      drug events, hospitalisation and increased mortality. The purpose of this study
      was to investigate the prevalence and factors associated with polypharmacy in
      older people with cancer. PATIENTS AND METHODS: Patients aged>=70 years (n=385)
      presenting to the medical oncology outpatient clinic at Royal Adelaide Hospital
      between January 2009 and July 2010 completed a structured data collection
      instrument. The instrument included domains related to medications, diagnoses,
      instrumental activities of daily living (IADLs), Karnofsky Performance Scale
      (KPS), physical function (SF-36), pain (ten-point visual analogue scale, VAS),
      weight loss (patient self-reported over previous 6 months), exhaustion (CES-D)
      and distress (ten-point VAS). Frailty was computed using Fried's frailty
      phenotype. Logistic regression was used to compute unadjusted and adjusted odds
      ratios (ORs) and 95% confidence intervals (CIs) for the association between
      polypharmacy (defined as five or more self-reported daily medications) and
      clinical parameters. RESULTS: Polypharmacy was present in 57% (n=221) of
      patients. When adjusting for age, gender and Charlson Comorbidity Index (CCI),
      polypharmacy was associated with being pre-frail (OR=2.35, 95%CI=1.43-3.86) and
      frail (OR=4.48, 95%CI=1.90-10.54) compared to being robust. When adjusting for
      age, gender, exhaustion, KPS, IADLs, pain and distress, polypharmacy was
      associated with higher CCI scores (OR=1.58, 95%CI=1.29-1.94) and poorer physical
      function (OR=1.13, 95%CI=1.06-1.20). CONCLUSIONS: Polypharmacy is highly
      prevalent in older people with cancer and associated with impaired physical
      function and being pre-frail and frail compared to being robust. Research is
      needed to identify strategies to minimize patients' medication regimens.

PMID- 24584692
TI  - A facile single-step synthesis of ternary multicore magneto-plasmonic
      nanoparticles.
AB  - We report a facile single-step synthesis of ternary hybrid nanoparticles (NPs)
      composed of multiple dumbbell-like iron-silver (FeAg) cores encapsulated by a
      silicon (Si) shell using a versatile co-sputter gas-condensation technique. In
      comparison to previously reported binary magneto-plasmonic NPs, the advantage
      conferred by a Si shell is to bind the multiple magneto-plasmonic (FeAg) cores
      together and prevent them from aggregation at the same time. Further, we
      demonstrate that the size of the NPs and number of cores in each NP can be
      modulated over a wide range by tuning the experimental parameters. 

PMID- 24584693
TI  - Clinical evaluation of the Roche Elecsys CMV IgG Avidity assay.
AB  - Congenital cytomegalovirus (CMV) infection has potentially severe consequences in
      newborns. The testing of pregnant women for CMV-specific antibodies may be useful
      for the identification of women at risk of transmitting the infection to the
      fetus. The determination of CMV IgG avidity helps to establish the timing of
      infection as IgG avidity matures during the course of infection. This study
      examines the performance of the Elecsys CMV IgG Avidity assay using preselected
      samples from patients at different phases of CMV infection. The Elecsys CMV IgG
      Avidity assay was tested at three sites using sequential samples from patients
      with recent primary CMV infection, as well as single samples from patients with
      recent primary or past CMV infection. The Elecsys assay discriminated well
      between early (low avidity) and late (high avidity) phases of infection in
      sequential serum samples. Overall, 98.8% of low-avidity samples corresponded to
      infection onset <180 days before sampling and 77.8% of all high-avidity results
      corresponded to infection onset >90 days before sampling. The assay's sensitivity
      was 90-97%, with specificity ranging from 89 to 100%, depending on the
      consideration of gray-zone avidity values. Single samples from recent primary or
      past infection showed similar distributions of avidity results. The Elecsys CMV
      IgG Avidity assay results are in agreement with preselected samples from patients
      with primary or past CMV infection, showing that the test is an adequate
      predictor of the phase of infection.

PMID- 24584694
TI  - Clinical outcomes of medial patellofemoral ligament reconstruction in patients
      with an increased tibial tuberosity-trochlear groove distance.
AB  - PURPOSE: Medial patellofemoral ligament (MPFL) reconstruction is performed to
      treat recurrent patellar dislocation (RPD). However, the effectiveness of MPFL
      reconstruction in patients with a severely lateralised tibial tuberosity remains
      unknown. In this study, the clinical outcomes of MPFL reconstruction in patients
      with an increased tibial tuberosity-trochlear groove (TT-TG) distance were
      examined. METHODS: A total of thirty-four patients who underwent MPFL
      reconstruction for RPD were retrospectively examined. Nineteen patients with a TT
      TG distance of >20 mm (increased TT-TG distance group) were compared with 15
      patients with a TT-TG distance of <20 mm (control group). Clinical outcomes of
      MPFL reconstruction were evaluated by occurrence of re-dislocation, Crosby and
      Insall grading system, apprehension sign, and Kujala and Lysholm scores. RESULTS:
      None of the patients reported re-dislocation. Apprehension sign remained in three
      patients in the increased TT-TG distance group and in one patient in the control
      group. According to the Crosby and Insall grading system, 9 patients (47%) were
      excellent, 9 (47%) were good, and 1 (5%) was fair to poor in the increased TT-TG
      distance group, while 6 (40%) were excellent and 9 (60%) were good in the control
      group. Kujala and Lysholm scores were significantly improved post-operatively in
      both groups. No significant correlations were observed between TT-TG distance and
      post-operative Kujala or Lysholm score. CONCLUSION: Overall clinical outcomes of
      MPFL reconstruction were favourable even in patients with an increased TT-TG
      distance. TT-TG distance of >20 mm may not be an absolute indication for
      medialisation of the tibial tuberosity when performing MPFL reconstruction. LEVEL
      OF EVIDENCE: Case-control study, Level III.

PMID- 24584695
TI  - Reduced mortality in former elite endurance athletes.
AB  - For centuries, the general consensus has been that vigorous, competitive exercise
      was harmful and shortened life expectancy. Recent data from prospective cohort
      studies conducted on marathon runners, professional cyclists, and Olympic
      athletes indicate, however, that regular intense endurance-exercise training has
      protective benefits against cardiovascular disease and premature death. There are
      still important questions to be answered, such as what is the optimal dose, in
      terms of both duration and intensity of training or competition, beyond which the
      health benefits of regular exercise stabilize or might even potentially
      disappear. 

PMID- 24584696
TI  - Molecular composition of the alveolar lining fluid in the aging lung.
AB  - As we age, there is an increased risk for the development of pulmonary diseases,
      including infections, but few studies have considered changes in lung surfactant
      and components of the innate immune system as contributing factors to the
      increased susceptibility of the elderly to succumb to infections. We and others
      have demonstrated that human alveolar lining fluid (ALF) components, such as
      surfactant protein (SP)-A, SP-D, complement protein C3, and alveolar hydrolases,
      play a significant innate immune role in controlling microbial infections.
      However, there is a lack of information regarding the effect of increasing age on
      the level and function of ALF components in the lung. Here we addressed this gap
      in knowledge by determining the levels of ALF components in the aging lung that
      are important in controlling infection. Our findings demonstrate that pro
      inflammatory cytokines, surfactant proteins and lipids, and complement components
      are significantly altered in the aged lung in both mice and humans. Further, we
      show that the aging lung is a relatively oxidized environment. Our study provides
      new information on how the pulmonary environment in old age can potentially
      modify mucosal immune responses, thereby impacting pulmonary infections and other
      pulmonary diseases in the elderly population.

PMID- 24584697
TI  - WNT3A gene polymorphisms are associated with bone mineral density variation in
      postmenopausal mestizo women of an urban Mexican population: findings of a
      pathway-based high-density single nucleotide screening.
AB  - Osteoporosis (OP) is a common skeletal disorder characterized by low bone mineral
      density (BMD) and is a common health problem in Mexico. To date, few genes
      affecting BMD variation in the Mexican population have been identified. The aim
      of this study was to investigate the association of single nucleotide
      polymorphisms (SNPs) located in genes of the Wnt pathway with BMD variation at
      various skeletal sites in a cohort of postmenopausal Mexican women. A total of
      121 SNPs in or near 15 Wnt signaling pathway genes and 96 ancestry informative
      markers were genotyped in 425 postmenopausal women using the Illumina GoldenGate
      microarray SNP genotyping method. BMD was measured by dual-energy X-ray
      absorptiometry in total hip, femoral neck, Ward's triangle, and lumbar spine.
      Associations were tested by linear regression for quantitative traits adjusting
      for possible confounding factors. SNP rs752107 in WNT3A was strongly associated
      with decreased total hip BMD showing the highest significance under the recessive
      model (P = 0.00012). This SNP is predicted to disrupt a binding site for microRNA
      149. In addition, a polymorphism of the Wnt antagonist DKK2 was associated with
      BMD in femoral neck under a recessive model (P = 0.009). Several LRP4, LRP5, and
      LRP6 gene variants showed site-specific associations with BMD. In conclusion,
      this is the first report associating Wnt pathway gene variants with BMD in the
      Mexican population.

PMID- 24584698
TI  - Rsf-1 overexpression in human prostate cancer, implication as a prognostic
      marker.
AB  - Rsf-1 (HBXAP) was recently reported to be overexpressed in various cancers and
      associated with the malignant behavior of cancer cells. However, the expression
      of Rsf-1 and its clinical significance in human prostate cancer have not been
      reported. In the present study, we analyzed the expression pattern of Rsf-1 in
      human prostate cancer tissues and found that Rsf-1 was overexpressed in 45 % of
      prostate cancer specimens. There was a significant association between Rsf-1
      overexpression and tumor stage (p=0.0039) and preoperative PSA level (p=0.015).
      Furthermore, Rsf-1 overexpression correlated with poor biomedical recurrence-free
      survival in prostate cancer patients (p<0.001). Rsf-1 overexpression could serve
      as an independent predictor for poor recurrence-free survival (p=0.012). In
      addition, small interfering RNA (siRNA) knockdown in DU145 cells with high
      endogenous Rsf-1 expression decrease cell proliferation, colony formation, and
      invasion. In conclusion, Rsf-1 is overexpressed in human prostate cancers and
      serves as a novel prognostic marker. Rsf-1 contributes to prostate cancer cell
      growth and invasion, which makes it a candidate therapeutic target.

PMID- 24584699
TI  - Long-term treatment of spontaneously hypertensive rats with losartan and
      molecular basis of modulating Ito of ventricular myocytes.
AB  - The present study aimed to determine the effect of chronic treatment with
      losartan on transient outward potassium current (Ito) and the expression levels
      of potassium voltage-gated channel subfamily D members 2 and 3 (Kv4.2 and 3) and
      voltage-gated potassium channel-interacting protein 2 (KChIP2) in rats.
      Spontaneously hypertensive (SH) rats and Wistar-Kyoto (WKY) rats were used in the
      study. The rats were divided into lo-SH and SH groups and los-WKY and WKY groups,
      respectively. Ito was recorded and expression levels of Kv4.2, Kv4.3 and KChIP2
      were measured by western blot analysis and quantitative polymerase chain
      reaction. Ito current density was smaller in SH compared with WKY, los-WKY and
      los-SH groups (P<0.01). Inactivation time constant of myocytes was larger in SH
      compared with WKY, los-WKY and los-SH groups (P<0.01). The mean levels of mRNA
      and protein of Kv4.2 and Kv4.3 were significantly lower in the SH compared with
      WKY, los-WKY and los-SH groups in vivo and in vitro (P<0.01). The Pearson
      statistical test showed no correlation between the expression levels of Kv4.2,
      Kv4.3, KChIP2 and the changes in blood pressure in the losartan treatment group.
      In conclusion, chronic blockade of angiotensin II type 1 receptors with losartan
      reversed SH rats' electrical remodeling and shortened action potential duration,
      which was associated with an increase in Ito density as the expression levels of
      Kv4.2, Kv4.3 increased and the expression levels of KChIP2 decreased. However,
      the expression levels of Kv4.2, Kv4.3 and KChIP2 were not correlated with the
      change in blood pressure in the losartan treatment group. Losartan may decrease
      the inactivation time by increasing the expression of KChIP2.

PMID- 24584700
TI  - Inhibition of high glucose-induced apoptosis by uncoupling protein 2 in human
      umbilical vein endothelial cells.
AB  - Studies have shown that an overproduction of mitochondrial reactive oxygen
      species (ROS) is an initiating cause in the pathogenesis of diabetic
      complications. However, uncoupling protein 2 (UCP2) can protect retinal vascular
      endothelial cells from damage by inhibiting the overproduction of mitochondrial
      ROS, although the protective mechanism involved is not completely clear. This
      study aimed to assess the effect and mechanism of UCP2 on the apoptosis of human
      umbilical vein endothelial cells (HUVECs). HUVECs were cultured in normal glucose
      (NG, 5.5 mmol/l) or high glucose (HG, 30 mmol/l) medium in the presence or
      absence of UCP2(+/+) lentiviral transfection. Lentivirus-mediated UCP2
      overexpression inhibited the apoptosis of HUVECs induced by HG. Treatment with HG
      resulted in the upregulation of caspase-3 and cytochrome c and the downregulation
      of Bcl-2 in vitro. Furthermore, compared with the NG group, the rate of apoptosis
      was significantly increased in the HG group. On day two post-infection, NG cells
      showed significantly greater HUVEC cell proliferation than HG cells. Notably,
      UCP2 overexpression inhibited these processes. Taken together, these results
      suggest that UCP2 promotes cell proliferation and inhibits HG-induced apoptosis
      in HUVECs via the Bcl-2 up- and downregulation of caspase-3 and cytochrome c in
      vitro. This may provide experimental evidence for the application of UCP2 as a
      new protective factor for diabetic complications, such as diabetic retinopathy.

PMID- 24584701
TI  - BSH-CP based 3D solid-state NMR experiments for protein resonance assignment.
AB  - We have recently presented band-selective homonuclear cross-polarization (BSH-CP)
      as an efficient method for CO-CA transfer in deuterated as well as protonated
      solid proteins. Here we show how the BSH-CP CO-CA transfer block can be
      incorporated in a set of three-dimensional (3D) solid-state NMR (ssNMR) pulse
      schemes tailored for resonance assignment of proteins at high static magnetic
      fields and moderate magic-angle spinning rates. Due to the achieved excellent
      transfer efficiency of 33 % for BSH-CP, a complete set of 3D spectra needed for
      unambiguous resonance assignment could be rapidly recorded within 1 week for the
      model protein ubiquitin. Thus we expect that BSH-CP could replace the typically
      used CO-CA transfer schemes in well-established 3D ssNMR approaches for resonance
      assignment of solid biomolecules.

PMID- 24584703
TI  - Stimulation of anaerobic biodegradation of DDT and its metabolites in a muck
      soil: laboratory microcosm and mesocosm studies.
AB  - The aim of this study was to evaluate the impact of selected electron donors and
      electron acceptors on the anaerobic biodegradation of DDT and its major
      metabolites in a muck soil with a long history of exposure to the pesticide. Loss
      of DDT was measured in anaerobic microcosms supplemented with H2, lactate, and
      acetate. The greatest loss of DDT (approximately 87 %) was observed in microcosms
      amended with lactate and no additional electron acceptor compared to the no
      additional electron donor or acceptor sets. An increase in measureable
      concentrations of DDx was observed in un-amended microcosms. In larger scale
      mesocosms, significant increases in dissolved organic carbon (DOC) corresponded
      with low redox potentials. Increases in DOC corresponded with sharp increases in
      measured concentrations of DDx, followed by a decrease in measured DDT
      concentrations in lactate-amended mesocosms. Our studies indicate that sorbed DDx
      is released upon anaerobic incubation, and that indigenous microorganisms capable
      of DDx degradation respond to lactate additions. Both the potential for release
      of sorbed DDx and the potential for biodegradation of DDx should be considered
      during remediation of DDx-contaminated organic soils at low redox potentials.

PMID- 24584702
TI  - Complete genome characterization of a novel enterovirus type EV-B106 isolated in
      China, 2012.
AB  - Human enterovirus B106 (EV-B106) is a recently identified member of enterovirus
      species B. In this study, we report the complete genomic characterization of an
      EV-B106 strain (148/YN/CHN/12) isolated from an acute flaccid paralysis patient
      in Yunnan Province, China. The new strain had 79.2-81.3% nucleotide and 89.1
      94.8% amino acid similarity in the VP1 region with the other two EV-B106 strains
      from Bolivia and Pakistan. When compared with other EV serotypes, it had the
      highest (73.3%) VP1 nucleotide similarity with the EV-B77 prototype strain CF496
      99. However, when aligned with all EV-B106 and EV-B77 sequences available from
      the GenBank database, two major frame shifts were observed in the VP1 coding
      region, which resulted in substantial (20.5%) VP1 amino acid divergence between
      the two serotypes. Phylogenetic analysis and similarity plot analysis revealed
      multiple recombination events in the genome of this strain. This is the first
      report of the complete genome of EV-B106. 

PMID- 24584707
TI  - A network map of the gastrin signaling pathway.

PMID- 24584708
TI  - Comparisons of cone electroretinograms after indocyanine green-, brilliant blue G
      , or triamcinolone acetonide-assisted macular hole surgery.
AB  - PURPOSE: To compare the function of retinal ganglion cells (RGCs) using the
      photopic negative response (PhNR) in patients who had undergone indocyaine green
      (ICG)-assisted, brilliant blue G (BBG)-assisted, or triamcinolone acetonide (TA)
      assisted internal limiting membrane (ILM) peeling during macular hole (MH)
      surgery. METHODS: Forty-eight eyes of 48 patients with a macular hole were
      randomly divided into those undergoing ICG-assisted, BBG-assisted, or TA-assisted
      vitrectomy (n = 16 for each group). Full-field cone ERGs were recorded before and
      1, 3, 6, 9, and 12 months postoperatively. The amplitudes and implicit times of
      the a-waves and b-waves and the amplitudes of the oscillatory potentials (OPs)
      and PhNRs were measured. The mean deviations (MDs) of standard automated
      perimetry and the best-corrected visual acuity (BCVA) were measured. The
      circumferential retinal nerve fiber layer (RNFL) thickness was evaluated by SD
      OCT. RESULTS: All macular holes were closed with a significant improvement of the
      BCVA and MD without differences among the groups. There was no significant
      difference between the preoperative and postoperative RNFL thickness. The
      implicit times of the a-waves and b-waves were significantly prolonged, and the
      SigmaOPs amplitude was significantly decreased postoperatively in all groups.
      These ERG changes were not significantly different among the groups. The
      postoperative PhNR amplitudes were significantly lower in the ICG group than in
      the BBG or TA group. CONCLUSIONS: The results indicate that the PhNR may detect
      subclinical impairments of RGCs caused by the possible toxic effect of ICG. This
      finding adds to the data that BBG and TA may be safer than ICG for use during MH
      surgery.

PMID- 24584709
TI  - Salvage therapy with bendamustine for methotrexate refractory recurrent primary
      CNS lymphoma: a retrospective case series.
AB  - There is comparatively limited therapy for recurrent primary central nervous
      system lymphoma (PCNSL). Salvage therapies include re-challenge with high-dose
      methotrexate (HD-MTX), whole brain radiotherapy, temozolomide, topotecan and
      premetrexed. Bendamustine is a novel bifunctional alkylator with established
      activity in B cell systemic lymphomas but never previously evaluated in PCNSL.
      The objective of the current study was to assess response and toxicity of
      bendamustine in recurrent PCNSL following prior salvage therapy in a
      retrospective case series. Twelve adults [six males; six females: median age 59
      years (range 43-74)] with HD-MTX refractory recurrent PCNSL were treated with
      bendamustine. All patients were treated at second recurrence following failure of
      prior salvage therapy. A cycle of bendamustine was defined as two consecutive
      days of treatment (100 mg/m(2)/day) administered once every 4 weeks (maximum
      number of cycles 6). Toxicities seen were Grade 2 (24 episodes in 10 patients)
      and 3 (10 episodes in 5 patients) only and included lymphopenia (8 patients),
      hyperglycemia (7 patients), fatigue (7 patients) and nausea (4 patients). The
      median number of cycles of therapy was 3.5 (range 1-6). Radiographic response was
      progressive disease in 5 (42%), stable disease in 1 (8%), partial response in 3
      (25%) and complete response in 3 (25%). Median progression free survival (PFS)
      was 3.5 months (range 1-14 months) and 6-month PFS was 33 %. In this small
      retrospective series of select patients with recurrent PCNSL refractory to HD
      MTX, bendamustine appears to have modest single agent activity with manageable
      toxicity. Confirmation in a larger series of similar patients is required.

PMID- 24584711
TI  - Long-term follow-up for cardiovascular disease after chemotherapy and/or
      radiotherapy for breast cancer in an unselected population.
AB  - PURPOSE: Whereas earlier research focused on specific patient groups, this study
      assessed the risk of cardiovascular disease (CVD) in an unselected population
      curatively treated for breast cancer (BC), compared with an age-matched random
      sample of controls. METHODS: Risks were determined in BC survivors and controls.
      CVD was divided into three categories: congestive heart failure, vascular cardiac
      diseases, and "other" cardiac diseases. Hazard ratios (HRs) and 95% confidence
      intervals (95% CI) adjusted for age, CVD, and CVD risk factors at baseline were
      determined by Cox regression analyses. RESULTS: All 561 survivors of BC
      experienced surgery of whom 229 received (neo)adjuvant radiotherapy, 145 received
      chemotherapy (with or without radiotherapy), and 187 received no adjuvant
      therapy. During follow-up (median 9; range 5-57 years), CVD occurred in 176/561
      (31%) survivors and in 398/1,635 (24%) controls. After radiotherapy, no increased
      risks of congestive heart failure (HR 0.5; 95% CI 0.2-1.8), vascular cardiac
      diseases (HR 1.1; 95% CI 0.7-1.7), or other cardiac diseases (HR 1.3; 95% CI 0.8
      2.3) were found compared with controls. Similar results were found after
      chemotherapy for congestive heart failure (HR 1.8; 95% CI 0.6-5.8), vascular
      cardiac diseases (HR 1.1; 95% CI 0.5-2.3), and other cardiac diseases (HR 1.2;
      95% CI 0.3-5.5). CONCLUSIONS: In an unselected population of BC survivors, no
      significant increased risk of CVD after radiotherapy and/or chemotherapy was
      found compared with controls. However, the HRs after chemotherapy were in-line
      with previous studies. Future studies should include more detailed information on
      treatment and more specific outcome measures.

PMID- 24584712
TI  - Towards waste free organic synthesis using nanostructured hybrid silicas.
AB  - As catalysis and organic synthesis come together again, the need for stable,
      selective and truly heterogeneous solid catalysts for clean and efficient
      synthetic organic chemistry has increased. Hybrid silica glasses obtained by the
      sol-gel nanochemistry approach can be successfully used for the waste-free
      synthesis of valued chemicals in various applications. This success derives from
      the deliberate chemical design of hybrid nanostructures capable of immobilizing
      and stabilizing organocatalytic species and unstable metal nanoparticles. The
      highly selective activity along with a broad scope and ease of application of
      these mesoporous materials to high-throughput reactions opens the route to
      faster, cleaner and more convenient processes for both small and large scale
      manufacturing of useful molecules. 

PMID- 24584713
TI  - Prognostic significance of calcium-sensing receptor in breast cancer.
AB  - The calcium-sensing receptor (CaSR) is a G-protein coupled receptor that is
      involved in tumor suppression of cancers. However, its role in breast cancer
      remains largely unknown. The aim of the study was to investigate the expression
      of CaSR in breast cancers and to evaluate its prognostic significance. We found
      that the protein levels of CaSR were significantly reduced in cancer lesion
      compared with its paired non-tumor tissues. By analyzing the expression of CaSR
      in a 148 cases of breast cancer tissue microarray (TMA) by immunohistochemistry,
      we found that patients with lower expression of CaSR were significantly
      associated with poor overall survival, cause-specific survival, and distant
      metastasis-free survival. The Cox multivariate analysis showed that CaSR was an
      independent prognostic significance for both overall survival and cause-specific
      survival of breast cancer patients. Our data confirmed the tumor suppressor role
      of CaSR and suggested that CaSR is an independent prognostic indicator of breast
      cancer. 

PMID- 24584714
TI  - Estrogen receptor alpha gene polymorphisms and risk of prostate cancer: a meta
      analysis involving 18 studies.
AB  - Genetic and epigenetic changes in the estrogen receptor alpha (ER-alpha) gene,
      according to multiple lines of evidence, might alter its expression and its
      downstream signaling thereby increasing the risk of developing prostate cancer.
      The purpose of this meta-analysis was to determine whether polymorphisms in two
      intronic restriction sites in the ER-alpha (PvuII and XbaI) gene contribute to
      prostate cancer. A literature search for eligible studies published before
      November 5, 2013 was conducted in the PubMed, Embase, China Biology Medicine
      (CBM), and CNKI databases. Pooled crude odds ratios (ORs) and their corresponding
      95 % confidence intervals (CIs) were calculated. Eighteen case-control and cohort
      studies were included in this meta-analysis with a total 4,884 prostate cancer
      cases and 10,134 healthy controls. Two common ER-alpha polymorphisms were
      examined: IVS1-397 C>T (a.k.a. the PvuII restriction site, rs2234693) and IVS1
      351 A>G (a.k.a. the XbaI restriction site, rs9340799). Results from this meta
      analysis showed that the PvuII polymorphism was not significantly associated with
      prostate cancer risk in any of the racial subgroups, either by allelic or
      genotypic frequencies. However, this meta-analysis revealed that the G allele in
      the XbaI polymorphism was associated with a statistically significant increase in
      the risk of prostate cancer. In a stratified analysis based on ethnicity, the
      XbaI G allele remained significantly correlated with an increased risk of
      prostate cancer in Africans; this correlation, however, was not found in
      Caucasians or Asians. In summary, a positive association correlation was observed
      between frequencies of the XbaI (A>G) polymorphism and prostate cancer,
      especially in Africans, but not such correlation was found with regard to the
      frequency of the PvuII (C>T) polymorphism.

PMID- 24584715
TI  - Modelling the use of insecticide-treated cattle to control tsetse and Trypanosoma
      brucei rhodesiense in a multi-host population.
AB  - We present a mathematical model for the transmission of Trypanosoma brucei
      rhodesiense by tsetse vectors to a multi-host population. To control tsetse and
      T. b. rhodesiense, a proportion, psi, of cattle (one of the hosts considered in
      the model) is taken to be kept on treatment with insecticides. Analytical
      expressions are obtained for the basic reproduction number, R0n in the absence,
      and R(0n)(T) in the presence of insecticide-treated cattle (ITC). Stability
      analysis of the disease-free equilibrium was carried out for the case when there
      is one vertebrate host untreated with insecticide. By considering three
      vertebrate hosts (cattle, humans and wildlife) the sensitivity analysis was
      carried out on the basic reproduction number (R(0n)(T)) in the absence and
      presence of ITC. The results show that R(03)(T) is more sensitive to changes in
      the tsetse mortality. The model is then used to study the control of tsetse and
      T. b. rhodesiense in humans through application insecticides to cattle either
      over the whole-body or to restricted areas of the body known to be favoured
      tsetse feeding sites. Numerical results show that while both ITC strategies
      result in decreases in tsetse density and in the incidence of T. b. rhodesiense
      in humans, the restricted application technique results in improved cost
      effectiveness, providing a cheap, safe, environmentally friendly and farmer based
      strategy for the control of vectors and T. b. rhodesiense in humans.

PMID- 24584716
TI  - Cyclotriphosphazene appended porphyrins and fulleropyrrolidine complexes as
      supramolecular multiple photosynthetic reaction centers: steady and excited
      states photophysical investigation.
AB  - New multiple photosynthetic reaction centers were constructed from
      cyclophosphazene decorated multiporphyrin chromophores and a fulleropyrrolidine
      having a pyridine ligand (FPY). The excited state electron transfer in the self
      assembled donor-acceptor assembly was investigated by using steady state
      absorption and emission, time-resolved emission spectroscopy and nanosecond laser
      flash photolysis. The effect of metal (Zn(2+)) coordination to porphyrin units in
      the multiporphyrin arrays on cyclophosphazine scaffold (P3N3Zn) was studied by
      comparing with metal free porphyrin assembly on a cyclophosphazene scaffold
      (P3N3). In P3N3Zn, the decrease of absorption and fluorescence intensity and the
      lowering of the amplitude of longer fluorescence lifetime with increase of FPY
      concentration reflect the formation of a ground state complex with an association
      constant of ~14,910 M(-1). When compared to the metal-free complex P3N3, the
      metal-coordinated derivative P3N3Zn exhibited shortening of the singlet and
      triplet state lifetimes and lowering of the singlet and triplet quantum yields.
      The cause of the decrease of the triplet quantum yields by insertion of zinc
      metal is discussed along with the possible non-planarity of the porphyrin ring.
      From the fluorescence lifetime measurements for the P3N3Zn-FPY mixture, it is
      proposed that self-assembly of the donor-acceptor complex leads to charge
      separated species with a rate constant of 7.1 * 10(9) s(-1). The decrease of
      triplet state intensity and lifetime of the P3N3Zn in the P3N3Zn-FPY complex from
      the nanosecond transient absorption studies support the occurrence of
      intermolecular electron transfer in the triplet state.

PMID- 24584717
TI  - miRNA profiling reveals a potential role of milk stasis in breast carcinogenesis.
AB  - The tumor microenvironment plays an important role in breast carcinogenesis. Milk
      acts as an important microenvironment of breast cancer, but its role in breast
      carcinogenesis is largely unknown. Milk stasis may exist in the breast for a
      number of years after breastfeeding. In the present study, we reported the first
      microRNA (miRNA) profiling of milk from patients with milk stasis. We identified
      266 known miRNAs and 271 novel miRNAs in 10 milk stasis only samples, 271 known
      miRNAs and 140 novel miRNAs in 10 milk stasis plus breast neoplasm samples by
      deep sequencing. miRNA profiles were different between the two groups.
      Furthermore, nine tumor suppressor miRNAs such as miR-29a, miR-146 and miR-223
      were significantly downregulated, while seven oncogenic miRNAs such as miR-451,
      miR-486, miR-107, miR-92 and miR-10 were significantly upregulated in the milk of
      milk stasis plus neoplasm patients. Three of the identified miRNAs (miR-140, miR
      21 and let-7a) were selected using real-time PCR, confirming that these miRNAs
      were highly expressed. The results also showed that the three miRNAs detected
      were more abundant in the milk than in the blood. In summary, the data suggested
      that miRNAs in milk from milk stasis patients may contribute to breast
      carcinogenesis and that they are more sensitive biomarkers for breast cancer than
      miRNAs in the blood.

PMID- 24584718
TI  - Seasonal trend and clinical presentation of Bacillus cereus bloodstream
      infection: association with summer and indwelling catheter.
AB  - Bacillus cereus, an opportunistic pathogen, can cause fatal infection. However,
      B. cereus bloodstream infections (BSIs) have not been well characterised. From
      2008 to 2013, B. cereus isolates from all of the specimens and patients with B.
      cereus BSIs were identified. Environmental samples were collected to detect B.
      cereus contamination. We also characterised the clinical presentation of B.
      cereus BSI through analyses of risk factors for BSI and mortality. A total of 217
      clinical B. cereus isolates was detected. Fifty-one patients with nosocomial
      infections were diagnosed as B. cereus BSI, and 37 had contaminated blood
      cultures. The number of B. cereus isolates and BSI patients was significantly
      greater from June to September than from January to April (4.9 vs. 1.5 per month
      and 1.2 vs. 0.2, respectively). All BSIs were nosocomial and related to central
      or peripheral vascular catheter. Urinary catheter [odds ratio (OR) 6.93, 95%
      confidence interval (CI) 2.40-20.0] was the independent risk factor associated
      with BSI patients when compared to patients regarded as contaminated. In-hospital
      mortality among BSI patients was 20% and was associated with urinary catheter (OR
      34.7, 95 % CI 1.89-63.6) and higher Charlson index (OR 1.99, 95 % CI 1.26-3.12).
      The number of B. cereus isolates and BSI increased during summer. Inpatients with
      indwelling vascular or urinary catheters should be carefully monitored for
      potential B. cereus BSIs.

PMID- 24584728
TI  - Accuracy and feasibility of dual fluoroscopy and model-based tracking to quantify
      in vivo hip kinematics during clinical exams.
AB  - Accurate measurements of in-vivo hip kinematics may elucidate the mechanisms
      responsible for impaired function and chondrolabral damage in hips with
      femoroacetabular impingement (FAI). The objectives of this study were to quantify
      the accuracy and demonstrate the feasibility of using dual fluoroscopy to measure
      in-vivo hip kinematics during clinical exams used in the assessment of FAI. Steel
      beads were implanted into the pelvis and femur of two cadavers. Specimens were
      imaged under dual fluoroscopy during the impingement exam, FABER test, and
      rotational profile. Bead locations measured with model-based tracking were
      compared with those measured using dynamic radiostereometric analysis. Error was
      quantified by bias and precision, defined as the average and standard deviation
      of the differences between tracking methods, respectively. A normal male
      volunteer was also imaged during clinical exams. Bias and precision along a
      single axis did not exceed 0.17 and 0.21 mm, respectively. Comparing kinematics,
      positional error was less than 0.48 mm and rotational error was less than 0.58
      degrees . For the volunteer, kinematics were reported as joint angles and bone
      bone distance. These results demonstrate that dual fluoroscopy and model-based
      tracking can accurately measure hip kinematics in living subjects during clinical
      exams of the hip. 

PMID- 24584734
TI  - The change and development of statistical methods used in research articles in
      child development 1930-2010.
AB  - The evolution of developmental psychology has been characterized by the use of
      different quantitative and qualitative methods and procedures. But how does the
      use of methods and procedures change over time? This study explores the change
      and development of statistical methods used in articles published in Child
      Development from 1930 to 2010. The methods used in every article in the first
      issue of every volume were categorized into four categories. Until 1980
      relatively simple statistical methods were used. During the last 30 years there
      has been an explosive use of more advanced statistical methods employed. The
      absence of statistical methods or use of simple methods had been eliminated.

PMID- 24584735
TI  - Inhibition of post-translational N-glycosylation by HRD1 that controls the fate
      of ABCG5/8 transporter.
AB  - N-glycosylation of proteins in endoplasmic reticulum is critical for protein
      quality control. We showed here a post-translational N-glycosylation affected by
      the HRD1 E3 ubiquitin ligase. Both WT- and E3-defective C329S-HRD1 decreased the
      level of high mannose form of ABCG8, a protein that heterodimerizes with ABCG5 to
      control sterol balance. Meanwhile, HRD1 increased the non-glycosylated ABCG8
      regardless of its E3 activity, thereby suppressing full maturation of ABCG5/8
      transporter. Pulse chase and mutational analysis indicated that HRD1 inhibits
      STT3B-dependent post-translational N-glycosylation of ABCG8. Whereas, HRD1 had
      only slight effect on the N-glycosylation status of ABCG5; rather it accelerated
      ABCG5 degradation in an E3 activity-dependent manner. Finally, RMA1, another E3
      ubiquitin ligase, accelerated the degradation of both ABCG5 and ABCG8 via E3
      activity-dependent manner. HRD1 and RMA1 may therefore be negative regulators of
      disease-associated transporter ABCG5/ABCG8. The findings also highlight the
      unexpected E3 activity-independent role of HRD1 in the regulation of N
      glycosylation. 

PMID- 24584736
TI  - Risk prediction model for heart failure and cardiomyopathy after adjuvant
      trastuzumab therapy for breast cancer.
AB  - BACKGROUND: Adjuvant trastuzumab improves survival for women with human epidermal
      growth factor receptor 2-positive breast cancer, but increases risk for heart
      failure (HF) and cardiomyopathy (CM). However, clinical trials may underestimate
      HF/CM risk because they enroll younger subjects with fewer cardiac risk factors.
      We sought to develop a clinical risk score that identifies older women with
      breast cancer who are at higher risk of HF or CM after trastuzumab. METHODS AND
      RESULTS: Using the Surveillance, Epidemiology and End Results (SEER)-Medicare
      database, we identified women with breast cancer who received adjuvant
      trastuzumab. Using a split-sample design, we used a proportional hazards model to
      identify candidate predictors of HF/CM in a derivation cohort. A risk score was
      constructed using regression coefficients, and HF/CM rates were calculated in the
      validation cohort. The sample consisted of 1664 older women (mean age 73.6 years)
      with 3-year HF/CM rate of 19.1%. A risk score consisting of age, adjuvant
      chemotherapy, coronary artery disease, atrial fibrillation or flutter, diabetes
      mellitus, hypertension, and renal failure was able to classify HF/CM risk into
      low (0 to 3 points), medium (4 to 5 points), and high (>=6 points) risk strata
      with 3-year rates of 16.2%, 26.0%, and 39.5%, respectively. CONCLUSIONS: A 7
      factor risk score was able to stratify 3-year risk of HF/CM after trastuzumab
      between the lowest and highest risk groups by more than 2-fold in a Medicare
      population. These findings will inform future research aimed at further
      developing a clinical risk score for HF/CM for breast cancer patients of all
      ages.

PMID- 24584737
TI  - Acute intravenous injection of serelaxin (recombinant human relaxin-2) causes
      rapid and sustained bradykinin-mediated vasorelaxation.
AB  - BACKGROUND: A recent clinical trial (RELAXin in Acute Heart Failure [RELAX-AHF])
      demonstrated that 48 hours of continuous intravenous infusion of the vasorelaxant
      peptide serelaxin (recombinant human relaxin-2) to patients with acute heart
      failure reduced cardiovascular mortality at 180 days. The persistence of a
      vasorelaxant response as a potential mechanism for this long-term benefit and the
      vascular effects of a bolus intravenous injection of serelaxin have not been
      examined. This study investigates changes in resistance artery reactivity and
      passive mechanical wall properties following an intravenous serelaxin injection
      and whether these vascular effects persist in the absence of detectable
      circulating serelaxin. METHODS AND RESULTS: Male rats were injected with 13.3
      MUg/kg serelaxin into the tail vein; mesenteric arteries were assessed 3 and 24
      hours after treatment by using wire-myography. Serelaxin increased basal nitric
      oxide synthase activity and reduced maximal contraction to endothelin-1 at 3
      hours after administration. Serelaxin treatment also selectively enhanced
      bradykinin-mediated endothelium-dependent relaxation. This effect was sustained
      for 24 hours in the absence of circulating serelaxin. Serelaxin-mediated
      augmentation of bradykinin-evoked relaxation involved endothelium-derived
      hyperpolarization after 3 hours and prostacyclin-mediated relaxation after 24
      hours. Furthermore, upregulation of inducible nitric oxide synthase,
      phosphorylation of protein kinase B at Ser473 and endothelial nitric oxide
      synthase at Ser1177 was observed at 24 hours after serelaxin injection. There
      were no effects of serelaxin on passive arterial wall stiffness. CONCLUSION: Our
      data show that a bolus intravenous injection of serelaxin modulates endothelial
      vasodilator function 3 hours after administration, an effect that was sustained
      for 24 hours. The prolonged bradykinin-mediated vasorelaxation is principally
      mediated through prostacyclin.

PMID- 24584738
TI  - The importance of Purkinje activation in long duration ventricular fibrillation.
AB  - BACKGROUND: The mechanisms that maintain long duration ventricular fibrillation
      (LDVF) are unclear. The difference in distribution of the Purkinje system in dogs
      and pigs was explored to determine if Purkinje activation propagates to stimulate
      working myocardium (WM) during LDVF and WM pacing. METHODS AND RESULTS: In-vivo
      extracellular recordings were made from 1044 intramural plunge and epicardial
      plaque electrodes in 6 pig and 6 dog hearts. Sinus activation propagated
      sequentially from the endocardium to the epicardium in dogs but not pigs. During
      epicardial pacing, activation propagated along the endocardium and traversed the
      LV wall almost parallel to the epicardium in dogs, but in pigs propagated away
      from the pacing site approximately perpendicular to the epicardium. After 1
      minute of VF, activation rate near the endocardium was significantly faster than
      near the epicardium in dogs (P<0.01) but not pigs (P>0.05). From 2 to 10 minutes
      of LDVF, recordings exhibiting Purkinje activations were near the endocardium in
      dogs (P<0.01) but were scattered transmurally in pigs, and the WM activation rate
      in recordings in which Purkinje activations were present was significantly faster
      than the WM activation rate in recordings in which Purkinje activations were
      absent (P<0.01). In 10 isolated perfused dog hearts, the LV endocardium was
      exposed and 2 microelectrodes were inserted into Purkinje and adjacent myocardial
      cells. After 5 minutes of LDVF, mean Purkinje activation rate was significantly
      faster than mean WM activation rate (P<0.01). CONCLUSION: These extracellular and
      intracellular findings about activation support the hypothesis that Purkinje
      activation propagates to stimulate WM during sinus rhythm, pacing, and LDVF.

PMID- 24584739
TI  - Endothelial cell-, platelet-, and monocyte/macrophage-derived microparticles are
      elevated in psoriasis beyond cardiometabolic risk factors.
AB  - BACKGROUND: Psoriasis, especially when severe, is a risk factor for
      cardiometabolic disease beyond traditional risk factors. The mechanism of
      atherogenesis in psoriasis remains unknown. Cell membrane vesicles (ie,
      microparticles), released upon cell activation or apoptosis, have recently been
      associated with cardiometabolic disease and may play a pathogenic role.
      Microparticle levels, particularly from endothelial cells and platelets, are
      elevated in patients with cardiovascular disorders, metabolic syndrome, other
      inflammatory diseases, autoimmune conditions, and have been shown to be
      predictive of cardiovascular outcomes. METHODS AND RESULTS: Concentrations of
      microparticles with positive expression for any of 7 cell surface markers
      (Annexin V, CD3, CD31, CD41a, CD64, CD105, and CD144) were measured in blood
      samples from psoriasis patients (n=53) and control subjects without psoriasis
      (n=41). Platelet-free plasma was separated from whole blood by one-step
      centrifugation for microparticle analysis. Microparticles were fluorescently
      labeled and characterized by flow cytometry. Higher concentrations of CD105
      (5.5/MUL versus 2.5/MUL, P<0.001), CD31 (31/MUL versus 18/MUL, P=0.002), CD41a
      (50/MUL versus 22/MUL, P<0.001), and CD64 (5.0/MUL versus 4.1/MUL, P=0.02) singly
      positive microparticles corresponding to endothelial cell-, platelet-, and
      monocyte/macrophage-derived microparticles, respectively, were found in psoriasis
      patients compared with controls. These differences persisted after adjustment for
      traditional cardiometabolic risk factors including body mass index. CONCLUSIONS:
      Increased microparticle concentrations, independent of cardiometabolic risk
      factors, in patients with psoriasis suggest that the presence of increased
      endothelial cell, platelet, and monocyte/macrophage activation with cell turnover
      may contribute to the heightened atherogenesis associated with psoriasis.

PMID- 24584740
TI  - Cardiovascular and mortality risk of apparent resistant hypertension in women
      with suspected myocardial ischemia: a report from the NHLBI-sponsored WISE Study.
AB  - BACKGROUND: Women are more likely than men to develop resistant hypertension,
      which is associated with excess risk of major adverse outcomes; however, the
      impact of resistant hypertension in women with ischemia has not been explicitly
      studied. In this Women's Ischemia Syndrome Evaluation (WISE) analysis, we
      assessed long-term adverse outcomes associated with apparent treatment-resistant
      hypertension (aTRH) among women with suspected myocardial ischemia referred for
      coronary angiography. METHODS AND RESULTS: Women (n=927) were grouped according
      to baseline blood pressure (BP): normotensive (no hypertension history, BP
      <140/90 mm Hg, no antihypertensive drugs); controlled (BP <140/90 mm Hg and a
      hypertension diagnosis or on 1 to 3 drugs); uncontrolled (BP >=140/90 mm Hg on
      <=2 drugs); or aTRH (BP >=140/90 mm Hg on 3 drugs or anyone on >=4 drugs).
      Adverse outcomes (first occurrence of death [any cause], nonfatal myocardial
      infarction, nonfatal stroke, or hospitalization for heart failure or angina) were
      collected over 10 years of follow-up. Apparent treatment-resistant hypertension
      prevalence was 10.4% among those with hypertension. Women with aTRH had a greater
      incidence of adverse outcomes, compared with normotensive women (adjusted hazard
      ratio [HR], 3.25; 95% confidence interval [CI], 1.94 to 5.43), and women with
      controlled (HR, 1.77; 95% CI, 1.26 to 2.49) and uncontrolled (HR, 1.62; 95% CI,
      1.15 to 2.27) hypertension; outcome differences were evident early in follow-up.
      Risk of all-cause death was greater in the aTRH group, compared to the
      normotensive women and women with controlled and uncontrolled hypertension.
      CONCLUSIONS: In this cohort of women with evidence of ischemia, aTRH was
      associated with a profoundly increased long-term risk of major adverse events,
      including death, that emerged early during follow-up.

PMID- 24584741
TI  - Acute hypertriglyceridemia induces platelet hyperactivity that is not attenuated
      by insulin in polycystic ovary syndrome.
AB  - BACKGROUND: Atherothrombosis is associated with platelet hyperactivity.
      Hypertriglyceridemia and insulin resistance (IR) are features of polycystic ovary
      syndrome (PCOS). The effect of induced hypertriglyceridemia on IR and platelet
      function was examined in young women with PCOS. METHODS AND RESULTS: Following
      overnight fasting, 13 PCOS and 12 healthy women were infused with saline or 20%
      intralipid for 5 hours on separate days. Insulin sensitivity was measured using a
      hyperinsulinemic euglycaemic clamp in the final 2 hours of each infusion.
      Platelet responses to adenosine diphosphate (ADP) and prostacyclin (PGI2) were
      measured by flow cytometric analysis of platelet fibrinogen binding and P
      selectin expression using whole blood taken during each infusion (at 2 hours) and
      at the end of each clamp. Lipid infusion increased triglycerides and reduced
      insulin sensitivity in both controls (median, interquartile range ) (5.25 [3.3,
      6.48] versus 2.60 [0.88, 3.88] mg kg(-1) min(-1), P<0.001) and PCOS (3.15 [2.94,
      3.85] versus 1.06 [0.72, 1.43] mg kg(-1) min(-1), P<0.001). Platelet activation
      by ADP was enhanced and ability to suppress platelet activation by PGI2
      diminished during lipid infusion in both groups when compared to saline.
      Importantly, insulin infusion decreased lipid-induced platelet hyperactivity by
      decreasing their response to 1 MUmol/L ADP (78.7% [67.9, 82.3] versus 62.8%
      [51.8, 73.3], P=0.02) and increasing sensitivity to 0.01 MUmol/L PGI2 (67.6%
      [39.5, 83.8] versus 40.9% [23.8, 60.9], P=0.01) in controls, but not in PCOS.
      CONCLUSION: Acute hypertriglyceridemia induced IR, and increased platelet
      activation in both groups that was not reversed by insulin in PCOS subjects
      compared to controls. This suggests that platelet hyperactivity induced by acute
      hypertriglyceridemia and IR could contribute athero-thrombotic risk. CLINICAL
      TRIAL REGISTRATION URL: www.isrctn.org. Unique Identifier: ISRCTN42448814.

PMID- 24584742
TI  - Overcoming the barriers to palliative care referral for patients with advanced
      heart failure.

PMID- 24584743
TI  - tURn the lights on: mitochondrial transport-RNAs and cardiovascular disease.

PMID- 24584744
TI  - Survival by the fittest: hospital-level variation in quality of resuscitation
      care.

PMID- 24584745
TI  - Splenectomy is modifying the vascular remodeling of thrombosis.
AB  - BACKGROUND: Splenectomy is a clinical risk factor for complicated thrombosis. We
      hypothesized that the loss of the mechanical filtering function of the spleen may
      enrich for thrombogenic phospholipids in the circulation, thereby affecting the
      vascular remodeling of thrombosis. METHODS AND RESULTS: We investigated the
      effects of splenectomy both in chronic thromboembolic pulmonary hypertension
      (CTEPH), a human model disease for thrombus nonresolution, and in a mouse model
      of stagnant flow venous thrombosis mimicking deep vein thrombosis. Surgically
      excised thrombi from rare cases of CTEPH patients who had undergone previous
      splenectomy were enriched for anionic phospholipids like phosphatidylserine.
      Similar to human thrombi, phosphatidylserine accumulated in thrombi after
      splenectomy in the mouse model. A postsplenectomy state was associated with
      larger and more persistent thrombi. Higher counts of procoagulant platelet
      microparticles and increased leukocyte-platelet aggregates were observed in mice
      after splenectomy. Histological inspection revealed a decreased number of
      thrombus vessels. Phosphatidylserine-enriched phospholipids specifically
      inhibited endothelial proliferation and sprouting. CONCLUSIONS: After
      splenectomy, an increase in circulating microparticles and negatively charged
      phospholipids is enhanced by experimental thrombus induction. The initial
      increase in thrombus volume after splenectomy is due to platelet activation, and
      the subsequent delay of thrombus resolution is due to inhibition of thrombus
      angiogenesis. The data illustrate a potential mechanism of disease in CTEPH.

PMID- 24584746
TI  - Heart failure and breast cancer therapies: moving towards personalized risk
      assessment.

PMID- 24584748
TI  - Management of aggressive pituitary adenomas and pituitary carcinomas.
AB  - Pituitary tumors are benign but not uncommonly invade locally into adjacent
      tissues such as the cavernous sinus and dura. Some of these invasive tumors
      exhibit varying degrees of resistance to standard therapy and tend to recur.
      Early prediction of which pituitary tumors will recur and/or exhibit an invasive
      phenotype remains difficult despite introduction of several tissue-based
      molecular markers. Management of these recurrent invasive pituitary tumors
      usually comprises combination medical, surgical and radiation therapy but in some
      instances is suboptimal. Earlier diagnosis of invasive/recurrent pituitary tumor
      and application of aggressive multi-modal therapy at presentation may be
      advantageous in some cases. Clinical trials to develop additional therapeutic
      options are needed for this subgroup of pituitary tumors. Although it is not yet
      possible to diagnose at presentation, the subset of pituitary tumors that will
      become invasive and/or recurrent pituitary tumors, broader use of molecular
      markers and standardization of histopathological criteria for "atypical"
      pituitary tumor features have assisted earlier diagnosis. Aggressive therapy
      early in disease may be warranted and exploration of recently available targeted
      therapies may improve disease management. 

PMID- 24584752
TI  - Abstracts of the 80th Annual Meeting of the German Society for Experimental and
      Clinical Pharmacology and Toxicology, April 1-3, 2014, Hannover, Germany.

PMID- 24584749
TI  - Stereotactic radiosurgery for cavernous sinus hemangiomas.
AB  - We performed this retrospective study to analyze the outcome of patients with
      cavernous sinus hemangioma (CSH) after stereotactic radiosurgery (SRS). We
      analyzed 19 patients with CSHs who were treated with SRS between 1998 and 2011.
      The median age of the patients was 50 years (range, 35-73 years), and 16 (84.2%)
      of the patients were female. SRS was performed as a primary treatment for 18
      patients and to treat a residual lesion after surgical resection in one patient.
      Nine (47.4%) patients had cranial neuropathies in 14 cranial nerves before SRS,
      whereas five (26.3%) patients were initially asymptomatic. The mean volume of the
      CSHs was 6.1 +/- 7.2 cm(3) (range, 0.3-32.3 cm(3)), and the median marginal dose
      at the 50% isodose line was 14.5 Gy (range, 11.5-16.0 Gy). The mean follow-up
      period was 37 months (range, 12-85 months). At the last follow-up, the lesion
      volume had decreased in all patients. The average tumor volume had decreased to
      26% (range, 0-70%) of the initial volume at the last follow-up MRI. The first
      follow-up MRI, performed 6.1 +/- 1.0 months after the SRS, showed that the tumor
      volume had decreased to 41% (range, 0-88%) of the initial volume. All 14 of the
      cranial neuropathies observed before SRS had improved, with complete remission in
      12 (85.7%) cranial nerves and partial remission in two (14.3%). There were no
      radiation-induced neuropathies or complications during the follow-up period. SRS
      appears to be an effective and safe treatment modality for the management of
      CSHs.

PMID- 24584753
TI  - SUMOylation proteins in breast cancer.
AB  - Small Ubiquitin-like Modifier proteins (or SUMO) modify the function of protein
      substrates involved in various cellular processes including DNA damage response
      (DDR). It is becoming apparent that dysregulated SUMO contribute to
      carcinogenesis by affecting post-transcriptional modification of key proteins. It
      is hypothesised that SUMO contributes to the aggressive nature of breast cancer
      particularly those associated with features similar to breast carcinoma arising
      in patients with BRCA1 germline mutations. This study aims to assess the clinical
      and biological significance of three members of SUMO in a well-characterised
      annotated series of BC with emphasis on DDR. The study cohort comprised primary
      operable invasive BC including tumours from patients with known BRCA1 germline
      mutations. SUMO proteins PIAS1, PIAS4 and UBC9 were assessed using
      immunohistochemistry utilising tissue microarray technology. Additionally, their
      expression was assessed using reverse phase protein microarray utilising
      different cell lines. PIAS1 and UBC9 showed cytoplasmic and/or nuclear expression
      while PIAS4 was detected only in the nuclei. There was a correlation between
      subcellular localisation and expression of the nuclear transport protein KPNA2.
      Tumours showing positive nuclear/negative cytoplasmic expression of SUMO featured
      good prognostic characteristics including lower histologic grade and had a good
      outcome. Strong correlation with DDR-related proteins including BRCA1, Rad51,
      ATM, CHK1, DNA-PK and KU70/KU80 was observed. Correlation with ER and BRCA1 was
      confirmed using RPPA on cell lines. SUMO proteins seem to play important role in
      BC. Not only expression but also subcellular location is associated with BC
      phenotype. 

PMID- 24584754
TI  - Bioactivity-guided identification to delineate the immunomodulatory effects of
      methanolic extract of Nigella sativa seed on human peripheral blood mononuclear
      cells.
AB  - OBJECTIVE: To study the immunomodulatory effects of Nigella sativa (NS) on human
      peripheral blood mononuclear cells (PBMCs) on a Phytohemagglutinin (PHA) and a
      non-PHA stimulated proliferation. METHODS: Cells isolated from human PBMCs which
      were treated with methanolic extract of NS for 48 h into two separate
      environments (PHA and non-PHA stimulated). Flow cytometry (for T helper/inducer
      cells and natural killer cells) and real time-polymerase chain reaction (PCR)
      assays for a few selected proinflammatory gene expressions were performed.
      RESULTS: Extracts from NS had an immunostimulating effect on non-PHA-stimulated
      proliferation of human PBMCs. In contrast, immunosuppressive activity was
      observed on PHA-stimulated proliferation of human PBMCs. CONCLUSION: This in
      vitro study revealed the effects of NS plant extract on nonspecifific cellular
      immune responses.

PMID- 24584755
TI  - Songling Xuemaikang Capsule () for primary hypertension: A systematic review of
      randomized controlled trials.
AB  - OBJECTIVE: To evaluate the effectiveness and safety of Songling Xuemaikang
      Capsule (, SXC) for the treatment of primary hypertension. METHODS: An extensive
      search including Cochrane Library, PubMed, Cochrane Central Register of
      Controlled Trials (CENTRAL), Chinese Biomedical Literature Database (CBM),
      Chinese National Knowledge Infrastructure (CNKI), Chinese Scientific Journal
      Database (VIP), KoreaMed, Japanese database, and online clinical trial registry
      websites was performed up to February 2013. Randomized controlled trials (RCTs)
      regarding SXC for the treatment of primary hypertension were searched without no
      language restrictions. The quality of each trial was assessed according to the
      Cochrane Reviewers' Handbook 5.0, and RevMan 5.0 provided by the Cochrane
      Collaboration. RESULT: A total of 17 RCTs involving 1,778 patients were included.
      Meta-analysis showed that there was no significant difference between SXC and
      antihypertensive agents on systolic blood pressure [mean difference (MD): -0.10 [
      4.83, 4.63]; P=0.97] and diastolic blood pressure (MD: 1.00 [-1.16, 3.16];
      P=0.36), but SXC combined with antihypertensive drugs was more effective in
      lowering systolic blood pressure (MD: -6.17 [-7.86, -4.49]; P<0.00001) and
      diastolic blood pressure (MD: -7.24 [-8.62, -5.85]; P<0.00001) compared with the
      antihypertensive drugs alone. CONCLUSIONS: SXC used alone or combined with
      antihypertensive drugs appear to be an effective treatment for lowering elevated
      blood pressure and improving symptoms in patients with primary hypertension.
      However, the conclusion cannot be drawn definitely due to the poor quality of the
      included studies. There is still an urgent need for well-designed, long-term
      studies to address the benefits of SXC for treating primary hypertension.

PMID- 24584756
TI  - Effects of the hydro-alcoholic extract of Nigella sativa on scopolamine-induced
      spatial memory impairment in rats and its possible mechanism.
AB  - OBJECTIVE: To evaluate the effect of Nigella sativa (NS) extract on memory
      performance and its possible mechanisms in scopolamine (Sco)-induced spatial
      memory impairment model using Morris water maze test. METHODS: Thirty-two male
      Wistar rats were randomly divided into four groups. The control group received
      saline instead of both NS extract and Sco. The Sco group was treated by saline
      for two weeks, and was injected by Sco (2 mg/kg, intraperitoneally) 30 min before
      each trail in Morris water maze test. Sco+NS 200 and Sco+NS 400 groups were daily
      treated by 200 or 400 mg/kg of NS (intraperitoneally) for two weeks,
      respectively, and were finally injected by Sco 30 min before Morris water maze
      test. The brains of animals were removed to determine the acetylcholinesterase
      (AChE) activity and oxidative stress criteria in cortical tissues. RESULTS: Time
      latency and path length in the Sco group were significantly higher than in the
      control group (P<0.01), while the Sco+NS 400 group showed a significantly shorter
      traveled path length and time latency compared with the Sco group (P<0.01). AChE
      activity in the cortical tissues of the Sco group was significantly higher than
      the control group (P<0.01), while AChE activity in the Sco+NS 200 and Sco+NS 400
      groups was lower than the Sco group (P<0.01). Following Sco administration,
      malondialdehyde (MDA) concentrations were increased (P<0.01) in comparison with
      the control group, while cortical total thiol content decreased (P<0.01).
      Pretreatment with extracts caused a significant elevation in cortical total thiol
      content (P<0.01) and reduction in cortical MDA concentration (P<0.01) compared
      with the Sco group. CONCLUSIONS: Hydro-alcoholic extract of NS prevents Sco
      induced spatial memory deficits and decreases the AChE activity as well as
      oxidative stress of brain tissues in rats. Our results support the traditional
      belief about the beneficial effects of NS in nervous system. Moreover, further
      investigations are needed for better understanding of this protective effect.

PMID- 24584758
TI  - Effects of 5-hydroxymethyl furfural extracted from Rehmannia glutinosa Libosch on
      the expression of signaling molecules relevant to learning and memory among
      hippocampal neurons exposed to high concentration of corticosterone.
AB  - OBJECTIVE: To determine the effects of 5-hydroxymethyl furfural (5-HMF), an
      extract of Rehmannia glutinosa Libosch, on several down-regulated signaling
      molecules involved in learning and memory in hippocampal neurons. METHODS: After
      cultured for 7 days, primary hippocampal neurons were divided into 5 groups:
      normal, corticosterone model, RU38486, 5-HMF, and donepezil group. Neuron
      survival rates were calculated 24 h later using SYTO13-PI double-fluorescence
      staining and an 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
      (MTT) assay. beta-galactosidase activity was also assayed. Protein expressed by
      the glucocorticoid receptor (GCR), brainderived neurotrophic factor (BDNF), and N
      methyl-D-aspartate receptor 2B (NR2B), as well as phosphorylationcyclic adenosine
      monophosphate (cAMP) response element binding protein (p-CREB), phosphorylation
      extracellular signal-regulated kinase (p-ERK), and phosphorylation-synapsin (p
      synapsin) were quantified with Western blot. RESULTS: Hippocampal neuron survival
      rates and the above-mentioned proteins were dramatically decreased (P<0.05), beta
      galactosidase activity was significantly increased in the model group. but the
      effect was reversed by 5-HMF, RU38486, and to a lesser extent by donepezil
      (P<0.05). CONCLUSION: 5-HMF extracts from the Chinese herb Rehmannia glutinosa
      Libosch could protect hippocampal neurons from glucocorticoid injury and from
      down-regulated signaling molecules in the GCR-BDNF-NR2B-p-ERK-p-CREB-p-synapsin
      signal transduction pathway.

PMID- 24584757
TI  - Therapeutic effect of dimethyl dimethoxy biphenyl dicarboxylate on collagen
      induced arthritis in rats.
AB  - OBJECTIVE: To study the effect of oral administration of dimethyl dimethoxy
      biphenyl dicarboxylate (DDB) on adjusting angiogeneic/inflammatory mediators and
      ameliorating the pathology of bones in rats with collagen-induced arthritis
      (CIA). METHODS: Wistar rat model of CIA was set up using bovine collagen type II.
      Fifty rats were divided into five groups randomly: normal, CIA model, DDB
      treatment, methotrexate (MTX) treatment, and combined DDB+MTX treatment. Ankle
      joints of rats were imaged with digital X-ray machine to show the destruction of
      joints. Fore and hind paw and knee joints were removed above the ankle joint then
      processed for haematoxylin and eosin staining. Plasma levels of vascular
      endothelial growth factor (VEGF), platelet derived growth factor, interleukin-8
      (IL-8), IL-4, tumor necrosis factor alpha (TNF-alpha), and cyclooxygenase-2 (COX
      2) were quantified by enzyme-linked immunosorbent assay. Nitric oxide levels were
      detected by Griess reagent. RESULTS: Compared with the CIA model group, a
      remarkable reduction in various angiogenic (VEGF and IL-8) and inflammatory
      mediators (TNF-alpha, IL-4 and COX-2) after treatment with DDB either alone or
      combined with MTX P<0.05 or P<0.01). Histopathological and X-ray findings were
      confirmatory to the observed DDB anti-arthritic effect. The DDB-treated group
      showed amelioration in signs of arthritis which appeared essentially similar to
      normal. CONCLUSION: Our data shed light on the therapeutic efficacy of DDB in
      experimental rheumatoid arthritis (RA) compared with a choice drug (MTX) and it
      may be offered as a second-line drug in the treatment of RA.

PMID- 24584767
TI  - Charge self-localization in pi-conjugated polymers by long range corrected hybrid
      functionals.
AB  - We systematically investigate the capability of hybrid functionals for describing
      charge self-localization in conjugated polymers, using the critical test that the
      spatial extension of a localized charge should be polymer length independent. We
      first compare the new long-range corrected (LRC) hybrids with conventional global
      hybrids and find that the former has a clear and important advantage over the
      latter in being significantly less spin contaminated. We then focus on LRC
      hybrids and investigate in detail the dependence of charge localization on the
      range parameter. We show that this parameter consistently needs to be about 0.2
      bohr(-1) or larger to produce self-localized charges across different polymers.
      We introduce a new measure to determine the charge localization length, and then
      consider how properties related to localized charges converge with the polymer
      length and how they depend on the range parameter. These properties include the
      reorganization energy in the Marcus theory for electron transfer and the lowest
      excitation energy of a polaron. We discuss parameter tuning to experimental
      results and also suggest 0.2 bohr(-1) without tuning for exploratory studies
      based on the preference for least spin contaminations. 

PMID- 24584779
TI  - A complex study of the fast blue luminescence of oxidized silicon nanocrystals:
      the role of the core.
AB  - Silicon nanocrystals (SiNCs) smaller than 5 nm are a material with strong visible
      photoluminescence (PL). However, the physical origin of the PL, which, in the
      case of oxide-passivated SiNCs, is typically composed of a slow-decaying red
      orange band (S-band) and of a fast-decaying blue-green band (F-band), is still
      not fully understood. Here we present a physical interpretation of the F-band
      origin based on the results of an experimental study, in which we combine
      temperature (4-296 K), temporally (picosecond resolution) and spectrally resolved
      luminescence spectroscopy of free-standing oxide-passivated SiNCs. Our complex
      study shows that the F-band red-shifts only by 35 meV with increasing
      temperature, which is almost 6 times less than the red-shift of the S-band in a
      similar temperature range. In addition, the F-band characteristic decay time
      obtained from a stretched-exponential fit decreases only slightly with increasing
      temperature. These data strongly suggest that the F-band arises from the core
      related quasi-direct radiative recombination governed by slowly thermalizing
      photoholes. 

PMID- 24584780
TI  - Interleukin-6 disrupts blood-testis barrier through inhibiting protein
      degradation or activating phosphorylated ERK in Sertoli cells.
AB  - It has been recently ascribed to several inflammatory cytokines (i.e. TGF-beta3,
      TNF-alpha, and IL-1) a functional role in regulating Sertoli cell blood-testis
      barrier (BTB) dynamics. In the testis, IL-6 inhibits meiotic DNA synthesis during
      the seminiferous epithelium cycle, reduces sperm motility and influences the
      secretion of transferrin and inhibin B by Sertoli cells. Also, it has been shown
      that IL-6 affects tight junction permeability in Sertoli cells, but, little is
      known about its role in regulating the BTB. The aim of this study was to
      investigate the molecular mechanisms by which IL-6 affects BTB dynamics. We show
      that IL-6 perturbs the integrity of the BTB, and alters the normal localization
      and steady-state levels of BTB integral membrane proteins. We demonstrated that
      IL-6 regulates the BTB by inhibiting the degradation of BTB constitutive proteins
      and activating ERK-MAPK pathways. Our results provide mechanistic insight into
      the roles of IL-6 in regulating BTB dynamics. 

PMID- 24584781
TI  - Ecto- and arbuscular mycorrhizal symbiosis can induce tolerance to toxic pulses
      of phosphorus in jarrah (Eucalyptus marginata) seedlings.
AB  - In common with many plants native to low P soils, jarrah (Eucalyptus marginata)
      develops toxicity symptoms upon exposure to elevated phosphorus (P). Jarrah
      plants can establish arbuscular mycorrhizal (AM) and ectomycorrhizal (ECM)
      associations, along with a non-colonizing symbiosis described recently. AM
      colonization is known to influence the pattern of expression of genes required
      for P uptake of host plants and our aim was to investigate this phenomenon in
      relation to P sensitivity. Therefore, we examined the effect on hosts of the
      presence of AM and ECM fungi in combination with toxic pulses of P and assessed
      possible correlations between the induced tolerance and the shoot P
      concentration. The P transport dynamics of AM (Rhizophagus irregularis and
      Scutellospora calospora), ECM (Scleroderma sp.), non-colonizing symbiosis
      (Austroboletus occidentalis), dual mycorrhizal (R. irregularis and Scleroderma
      sp.), and non-mycorrhizal (NM) seedlings were monitored following two pulses of
      P. The ECM and A. occidentalis associations significantly enhanced the shoot P
      content of jarrah plants growing under P-deficient conditions. In addition, S.
      calospora, A. occidentalis, and Scleroderma sp. all stimulated plant growth
      significantly. All inoculated plants had significantly lower phytotoxicity
      symptoms compared to NM controls 7 days after addition of an elevated P dose (30
      mg P kg(-1) soil). Following exposure to toxicity-inducing levels of P, the shoot
      P concentration was significantly lower in R. irregularis-inoculated and dually
      inoculated plants compared to NM controls. Although all inoculated plants had
      reduced toxicity symptoms and there was a positive linear relationship between
      rank and shoot P concentration, the protective effect was not necessarily
      explained by the type of fungal association or the extent of mycorrhizal
      colonization. 

PMID- 24584783
TI  - Communication among health care teams: a major challenge for the improvement of
      patient safety.

PMID- 24584782
TI  - Proteasome inhibitor MG132 inhibits the proliferation and promotes the cisplatin
      induced apoptosis of human esophageal squamous cell carcinoma cells.
AB  - Comprehensive treatment based on chemotherapy is regarded as the first-line
      treatment for patients with unresectable or metastatic esophageal squamous cell
      carcinoma (ESCC). However, chemoresistance is common among patients with ESCC.
      Therefore, there is a need to explore new therapeutic strategies or adjuvant
      drugs. One promising possibility is to use dietary agents that can increase tumor
      cell sensitivity to drugs. In this study, we initially investigated the antitumor
      activity of proteasome inhibitor MG132 in vitro and in vivo. Effects of MG132 on
      the enhancment of the anticancer functions of cisplatin were then investigated in
      human esophageal cancer EC9706 cells in relation to apoptosis and cell signaling
      events. Exposure of cells to MG132 resulted in a marked decrease in cell
      viability in a dose- and time-dependent manner. Administration of MG132 markedly
      inhibited tumor growth in the EC9706 xenograft model. MG132 significantly
      enhanced cisplatin-induced apoptosis in association with the activation of
      caspase-3 and -8. These events were accompanied by the downregulation of NF
      kappaB, which plays a key role in cell apoptosis. Taken together, these findings
      demonstrate a novel mechanism by which proteasome inhibitor MG132 potentiates
      cisplatin-induced apoptosis in human ESCC and inhibitory activity of tumor growth
      of the EC9706 xenograft model.

PMID- 24584784
TI  - The story of a father about the circumstances experienced in a Neonatal Intensive
      Care Unit.

PMID- 24584785
TI  - Communication during patient handoff in the areas of intensive care of a
      university hospital: a cross-sectional study.
AB  - OBJECTIVE: To assess how the quality of communication is perceived during patient
      handoff in areas of intensive care. MATERIALS AND METHODS: Cross-sectional study
      conducted at a university hospital. The study assessed the perception of the
      quality of information received during patient handoff and the chance of
      physicians working on-call shifts in intensive care areas mistaking the
      information of one patient with that of another one. RESULTS: Information was
      perceived as being "good" quality when patient handoff took place in pediatric
      areas (85.7%), it was conducted in a calm environment (74.4%), it was performed
      according to a case presentation system (82.9%), the physician was responsible
      for less than 17 patients (91%), and training on handoff communication had been
      provided (87.5%). No significant association with the rest of the analyzed
      outcome measures was observed. The chance of mistaking information of one patient
      with that of another one was perceived as "low" when handoff took place in
      pediatric areas (95.2%), it was performed according to a case presentation system
      (80%), there were not more than three interruptions (84.6%), the physician was
      responsible for less than 17 patients (90.9%), training on handoff communication
      had been provided (91.7%), and the physician was a staff doctor (77.1%).
      CONCLUSIONS: The quality of information received during patient handoff and the
      chance of mistaking the information of one patient with that of another one were
      associated with environmental, organizational and educational aspects that can
      potentially be improved.

PMID- 24584786
TI  - Effectiveness of a program to improve antibiotic use in children hospitalized in
      a children's tertiary care facility in Argentina.
AB  - INTRODUCTION: Inadequate antibiotic use is associated with an increased emergence
      of resistant microorganisms, higher morbidity and mortality rates, and an impact
      on public health. OBJECTIVE: To assess the effectiveness of a program aimed at
      improving the use of antimicrobials in patients hospitalized at Hospital
      Garrahan. MATERIAL AND METHODS: Prospective, longitudinal, before and after study
      with no control group. STUDY PERIOD: From November 1st, 2010 to June 30th, 2011.
      Patients receiving parenteral antibiotics were included. Newborn infants, burned
      patients and those receiving prophylactic antibiotics were excluded. The periods
      before and after implementing discussion and monitoring workshops for antibiotic
      prescription and distributing treatment guidelines were compared. An univariate
      analysis and a multiple logistic regression study were performed (STATA 8.0).
      RESULTS: In the pre-intervention period,376 patients were included; of them,
      35.6% had received inadequate treatment. The multiple regression analysis showed
      that the endpoints for inadequate antibiotic use were acute lower respiratory
      tract infection (OR: 3.80; 95% CI: 1.35-3.26; p=0.04), fever without a source in
      hospitalized patients (OR: 5.55; 95% CI: 2.43-12.6; p < 0.01), and febrile
      neutropenia (OR: 0.29; 95% CI: 0.10-0.7; p < 0.01). In the post-intervention
      period, 357 patients were included; 21.5% had received inadequate treatment. A
      reduction in inadequate antibiotic prescription was observed compared to the pre
      intervention period (p < 0.01). The multiple regression analysis showed that
      endpoints for inadequate use were skin and soft tissue infections (OR: 0.33; 95%
      CI: 0.13-0.93; p = 0.035), and febrile neutropenia (OR: 0.48; 95% CI: 0.220.94;
      p= 0.04). CONCLUSION: The program was effective and allowed to improve antibiotic
      prescription practices in hospitalized children.

PMID- 24584787
TI  - Physical fitness and future cardiovascular risk in argentine children and
      adolescents: an introduction to the ALPHA test battery.
AB  - INTRODUCTION: A high level of physical fitness is associated with cardiovascular
      health in children and adolescents. At present, there is no systematic
      implementation of a test battery to assess physical fitness at schools in
      Argentina. The main objective of this study was to implement the ALPHA test
      battery to determine the physical fitness of a sample made up of Argentine
      children and adolescents and to establish the proportion of subjects whose
      aerobic capacity is indicative of future cardiovascular risk. POPULATION AND
      METHODS: A sample of 1867 participants (967 girls) aged 6 to 19.5 years old
      assessed using the ALPHA test battery. Four components of physical fitness were
      measured: 1) morphological component: height, body weight, and waist
      circumference; 2) musculoskeletal component: standing long jump test; 3) motor
      component: speed/agility test (4x10 m shuttle run); 4) cardiorespiratory
      component: course-navette 20 m, shuttle run test and estimation of maximal oxygen
      consumption. The 5th, 25th, 50th, 75th, and 95th percentiles were estimated for
      the main tests. RESULTS: The mean body mass index was 20.8 kg/m2, and 7.8% of
      participants were classified as obese. In ddition, male participants had a better
      performance in all physical fitness tests when compared to girls (p< 0.001). An
      aerobic capacity indicative of cardiovascular risk was observed in 31.6% of all
      participants. CONCLUSIONS: Argentine male children and adolescents included in
      the sample showed higher levels of physical fitness. Such differences increase
      with age. Approximately one every three participants had an aerobic capacity
      indicative of future cardiovascular risk.

PMID- 24584788
TI  - Post discharge growth assessment in preterm infants: implications of adopting the
      WHO standards.
AB  - INTRODUCTION: The WHO standards have been used as a gold standard for growth
      assessment in preterm infants since 1986. The introduction of the WHO standards
      in Argentina could improve detection of sub-optimal growth. OBJECTIVE: To compare
      the proportion of growth retardation in terms of weight, body height and head
      circumference in preterm infants with a birth weight less than 1500 g (VLBW)
      assessed according to the WHO standards and the Sociedad Argentina de Pediatria
      (SAP) standards. POPULATION AND METHODS: Cohort study in VLBW newborn infants.
      Measurements included were weight, height and head circumferences measured at 40,
      53, 66, 79 and 92 postmenstrual weeks (+/-1 week). Sex was recorded as an
      independent outcome measure for both standards (WHO and SAP). Mean Z scores were
      analyzed for both standards using Student's test, and the difference of
      proportions was assessed using the c2 test (OR; 95% CI). RESULTS: Two hundred and
      four infants were included. No differences were observed in anthropometric
      outcome measures at birth by sex. A greater growth was seen in terms of weight
      and height as per the SAP standards compared to the WHO standards, which was more
      marked in male infants than female infants, and which diminished around their
      first year of life. Growth retardation in terms of height was observed in both
      males and females assessed with the WHO standards. No differences were observed
      in head circumference. A higher proportion of patients with a weight below 2
      standard deviations at 3 months old was found as per the WHO (p < 0.01; OR: 0.36;
      95% CI: 0.150.78), but that was not the case with height and head circumference.
      CONCLUSIONS: This study allows to suggest that changing the standards does not
      imply a significant modification in our follow-up practice over the first year of
      life of an infant.

PMID- 24584789
TI  - Assessment of the scientific output of Hospital de Ninos Pedro de Elizalde, 2000
      2011.
AB  - INTRODUCTION: Monitoring article submissions and publications developed by an
      institution is a suitable measure to assess its scientific output. OBJECTIVES: To
      estimate the proportion of research projects that were completed and had results
      submitted/published by a pediatric hospital; to describe research project design
      and characteristics; to outline limitations on research development or
      dissemination. METHODS: Descriptive and analytical study including scientific
      studies approved to be developed between 2000 and 2011. Each investigator was
      contacted and asked to participate in a survey on research development, result
      dissemination and possible reasons for not completing or disseminating a study.
      RESULTS: The survey was completed by the authors of 197 projects (60.9%
      completed, 16.2% ongoing, 12.7% cancelled, and 10.2% put off). Drug trials were
      most likely not to be completed. Of all completed projects (n = 120), 45.8% were
      clinical research studies, 43.3% were epidemiological studies, and 10% were
      related to health services. When analyzed by design, 77.5% were observational
      studies while 22.5% were experimental ones. In terms of scope, 69.1% were
      restricted to the hospital, 16.6% were international multicenter studies, and
      14.1% were national multicenter studies. Only 36.6% of projects received funding.
      Lack of time (20%) and insufficient sample size (10%) were the most commonly
      indicated reasons for non dissemination. A total of 78.3% of projects were
      presented in conferences and 37.5% were published. The presence of funding was
      the only independent predictor of publication. CONCLUSIONS: Of all approved
      projects, 60.9% were completed; of them, 78.3% were presented in conferences and
      37.5% were published. Drug trials were most likely not to be completed, and
      funded studies had more chances of being published.

PMID- 24584790
TI  - [Antidiuretic hormone, 2014].

PMID- 24584791
TI  - Intravitreal bevacizumab as single drug therapy for retinopathy of prematurity in
      12 patients.
AB  - Ophthalmological outcomes in a series of children with retinopathy of prematurity
      (ROP) in the threshold stage treated with intravitreal bevacizumab are reported.
      Twelve very low birth weight (VLBW) preterm infants who were administered
      intravitreal bevacizumab as monotherapy for retinopathy of prematurity in the
      threshold stage and in whom standard laser photocoagulation therapy was
      contraindicated were evaluated. Ophthalmological examinations were carried out
      and response to treatment, second interventions, and complications were
      evaluated. The gestational age of these patients was 26.3 +/- 1.8 weeks and their
      birth weight was 845 +/- 153 g. A good response was observed in eight cases,
      while four patients required to be reintervened with laser photocoagulation. No
      immediate complications were detected and there were no deaths.

PMID- 24584792
TI  - Severe Staphylococcus aureus infection in three pediatric intensive care units:
      analysis of cases of necrotizing pneumonia.
AB  - Staphylococcus aureus frequently affects human beings. Among clinical
      manifestations, necrotizing pneumonia is associated with a high mortality rate.
      Our objective is to describe the progress of severe Staphylococcus aureus
      infections in three intensive care units and analyze cases ofnecrotizing
      pneumonia in the period ranging from January 2011 to March 2013. Forty-three
      patients were studied, 76.7% had a community-acquired infection, and 31 had
      community-acquired methicillin-resistant Staphylococcus aureus. The main reason
      for admission was respiratory failure. Bacteremia was confirmed in 55.8% of
      cases. Mechanical ventilation was required in 86% of admitted patients, while 27
      patients developed septic shock. The length of stay in the intensive care unit
      was 13 (5-25) days, and the mortality rate was 14%. Necrotizing pneumonia was
      observed in 51% of cases. Conclusion. A high rate of community-acquired infection
      was identified. Necrotizing pneumonia was associated with a worse clinical
      course. 

PMID- 24584793
TI  - [Autoimmune hepatitis in children: current perspectives].

PMID- 24584794
TI  - [Accidents due to Lepidoptera: Hylesia nigricans (Berg, 1875) or "mariposa
      negra"].
AB  - Lepidoptera (butterflies, caterpillars and moths) biologic features make possible
      the contact between different instars and humans. The moth Hylesia nigricans is
      responsible for epidemic outbreaks in our country. It is called erucism when the
      contact is with caterpillars and lepidopterism when the contact is with moths. We
      perform an update of these important medical lepidopters. 

PMID- 24584795
TI  - [Skin and soft tissue infections in children: consensus on diagnosis and
      treatment].
AB  - Skin and soft tissue infections are a common reason for consultation in primary
      health care centers. Data from the local epidemiology of these infections are
      rare, but Staphylococcus aureus and Streptococcus pyogenes are known to be the
      major etiologic agents. The appearance in recent years of community-originated
      strains of methicillin-resistant S. aureus and erythromycin-resistant pyogenes
      raises controversy in the choice of initial empirical treatment. This national
      consensus is for pediatricians, dermatologists, infectologists and other health
      professionals. It is about clinical management, especially the diagnosis and
      treatment of community-originated skin and soft tissue infections in
      immunocompetent patients under the age of 19. 

PMID- 24584796
TI  - [Basic cardiopulmonary resuscitation courses for parents of newborns and
      infants].
AB  - Cardiopulmonary resuscitation (CPR) courses meet all the definitions of an
      educational activity for prevention of cardiac arrest death by risk patients'
      parents and/or the general population. The aim is to improve patients' home care
      and turn parents confident before their children are discharged from hospital,
      mainly from intensive care units. Currently these courses are part of discharge
      protocols in many neonatologist services although there are offers that exceed
      this target, and extend to other areas such as education and caregivers. Locally
      the experience of neonatal CPR at the Sociedad Argentina de Pediatria stands out
      in connection with delivering courses to high risk patients' parents as well as
      designing and spreading learning material. 

PMID- 24584797
TI  - [Pseudotumor cerebri].

PMID- 24584798
TI  - Lumbar disc herniation in a child with cystic fibrosis: case report.
AB  - We report a case of child with cystic fibrosis and lumbar disc herniation. An 8
      year-old boy presented with low back pain that exacerbated on coughing, sitting,
      walking, or bending and diminished when lying down. The straight leg raising test
      was positive when the right leg was lifted at 60 degrees. Crossed leg raising
      test was negative. Lumbar MRI revealed a L5-S1central disc protrusion.
      Conservative treatment was not effective and the patient underwent surgery.
      Postoperatively the patient experienced regression of the pain. To the best of
      our knowledge this is the first reported case of lumbar disc herniation in a
      child with cystic fibrosis. Although this case might be coincidental, thorough
      investigation of back pain, which is frequent in patients with cystic fibrosis,
      should be performed. 

PMID- 24584799
TI  - [Mauriac syndrome in Argentina in the XXI century: series of 5 cases].
AB  - Mauriac syndrome is associated with poor metabolic control of type 1 diabetes
      mellitus, hepatomegaly and elevated transaminases characterized by growth failure
      and delayed puberty, which may be reversible with good glycemic control. There
      are few references published in recent years following the introduction of
      glycemic self-monitoring, new insulins and intensified treatment. We describe a
      series of five patients evaluated in our service with Mauriac syndrome
      characteristics, conducting a literature review of cases in Argentina. 

PMID- 24584800
TI  - [Traumatic wound botulism].
AB  - Botulism is a rare illness caused by a potent neurotoxin produced by the
      bacterium of the Clostridium family. Clostridium botulinum is the most frequent
      one, but Clostridium baratti and Clostridium butyricum are also neurotoxins
      producers. There are seven neurotoxins types, A to G; A, B, E, F and G cause
      human botulism. Every neurotoxin type blocks cholinergic transmission at the
      myoneural junction. The least frequent syndrome results from Clostridium
      botulinum colonization of a wound and it is clinically similar to the other
      botulism syndromes, but with fever due to an infected wound. Disease should be
      suspected in lucid patient with a symmetric descending, flaccid paralysis. This
      syndrome appears within the first twenty days, but it could be present for weeks
      or months before the disease is diagnosed. This disease is poorly known, so to be
      diagnosed it requires a high index of suspicion. The treatment is a supportive
      one; administration of the specific antitoxin must be early in order to
      neutralize the toxin before the debridement and cleaning of the infected wound. 

PMID- 24584801
TI  - Macular exanthema in a child with rotavirus gastroenteritis: a case report.
AB  - Apart from gastroenteritis, rotavirus has been rarely implicated with some
      cutaneous disorders such as generalized maculo-papular exanthema, infantile acute
      hemorrhagic edema and Gianotti-Crosti syndrome. We report a 30-month old toddler
      boy who developed erythematous macular skin eruptions during the course of
      rotavirus gastroenteritis. To our knowledge, this is the first case in the
      literature reporting rotavirus-related macular erythematous lesions in a
      pediatric patient. We therefore would like to share our experience, to keep ro
      tavirus infection in the differential diagnosis of children with gastroenteritis
      and erythematous eruption. 

PMID- 24584802
TI  - [Linear IgA bullous dermatosis of childhood: case report].
AB  - Linear IgA bullous dermatosis is a rare acquired autoinmune vesiculobullous
      disease characterized by linear IgA deposit on the dermo-epidermal basement
      membrane observed with direct inmunofluorescence. The characteristic lesions are
      vesicles and tense serous bullae, which most often are grouped giving a "cluster
      of jewels" appearance. Differential diagnosis must be established with other
      autoimmune dermatosis, such as dermatitis herpetiformis and bullous pemphigoid.
      Dapsone is the first line therapy, with excellent response in a short period.
      This is a benign disease that tends to wax and wane in severity until it
      disappears spontaneously. We report the case of a 5-year-old girl presenting with
      bullous lesions, being diagnosed a linear IgA bullous dermatosis, with excellent
      response to dapsone in less than 2 weeks. 

PMID- 24584803
TI  - [Rapidly involuting congenital hemangiomas: twenty five case series].
AB  - Rapidly involuting congenital hemangiomas are very rare vascular tumours, that
      are characterized for being completely developed at birth and for involuting in a
      short period of time after birth. We describe a case series of 25 patients with
      rapidly involuting congenital hemangiomas. Twelve patients were male and 13
      female; they were all born at term. Lesions were small in 17 cases and big in 8.
      No patient needed active intervention and all lesions showed a rapid initial
      involution. 

PMID- 24584804
TI  - [Estricnotherapy in severe diphtheria: Efficacy of intensive treatment. 1939].

PMID- 24584805
TI  - Editorial.

PMID- 24584806
TI  - Review and classification of corneal topographers.
AB  - Corneal topography has, due to developments in refractive surgery and contact
      lens fitting, become a widely used diagnostic tool. Many types of topographers
      have been introduced, but there is some confusion on classification and
      subsequent principal possibilities of the various devices offered to the
      practitioner. The purpose of the study reported here was to make an inventory of
      developed devices, analyse the basic principles and create a classification based
      on optical principles. A literature search was done using Medline, the IBM Patent
      Server, and references found in articles and patents. This search resulted in a
      variety of descriptions that could be classified into 12 groups according to
      their use of light source and light-matter interaction of which four groups have
      representatives on the commercial market. This classification can be used by
      researchers and practitioners to gain insight into the possibilities of a given
      device in relation to the desired application. 

PMID- 24584807
TI  - Laser therapy in maintenance of the patency of expandable metal stents.
AB  - Re-establishment of the oesophageal lumen is the main focus of care in patients
      with dysphagia due to re-blockage of in situ expandable metal stent (EMS). A
      total of 51 patients aged 44-89 years were intubated with EMS for dysphagia due
      to inoperable oesophagogastric carcinoma. Of these patients, 25 required follow
      up endoscopy at variable intervals after stent insertion; 17 patients were found
      to have significant tumour in-growth (9), overgrowth (4) or both (4). All these
      patients were treated with Nd-YAG (70 W/s) or diode laser (30-50 W, continuous)
      for maintenance of satisfactory swallowing. The intensity of tumour ablation was
      similar with both types of lasers but four patients being treated with Nd-YAG
      laser developed deformity of EMS. This complication was not encountered with
      diode laser. The timing of the stent insertion should be carefully chosen since
      the longer the stent is in situ, the greater is the likelihood of tumour ingrowth
      or overgrowth. The combination of endoscopic laser therapy (ELT) and EMS may
      offer the best palliation, particularly when patient survival of several months
      is anticipated. ELT can effectively deal with tumour in-growth and overgrowth but
      care must be exercised in the use of Nd-YAG which can damage the structure of the
      EMS. 

PMID- 24584808
TI  - Laser Resistance of Endotracheal Tubes II: ObservedTemperature Rise and
      Theoretical Explanation.
AB  - An infrared camera was used to measure the temperature rise which takes place in
      endotracheal tubes exposed to a 20 W CO2 laser beam. It was seen that a metallic
      tube was heated up within 1 s to temperatures of 200-300 degrees C which was very
      destructive to the PVC conduits inside the tube. A compound tube, on the other
      hand, reached temperatures of only 60 degrees C at its inner surface after an
      exposure of 20 s. The experimental results can be explained by a physical model
      which uses the heat conduction and the heat capacities of both tubes. Whereas
      heat conduction in the metal tube is isotropic, heat conduction in the compound
      tube is anisotropic with a high conductivity along the outer surface and a low
      conductivity to the inside. This anisotropy and the cooling mechanism in the
      compound tube due to vaporising water are the reason for the high laser
      resistance of the tube. 

PMID- 24584809
TI  - Diffusing Fibre Tip for the Minimally Invasive Treatment of Liver Tumours by
      Interstitial Laser Coagulation (ILC): An Experimental Ex Vivo Study.
AB  - A newly developed diffusing laser applicator was examined for interstitial laser
      coagulation (ILC) of liver tumours. The applicator consisted of a matted quartz
      core and a quartz glass dome, also matted on its inner surface and sealed to the
      fibre. The applicator provided a homogeneous light intensity distribution over an
      active length of about 20 mm. Lesions were created in an ex-vivo porcine liver
      model using a Nd-YAG laser comparing the new diffusing tip with a Ringmode((r))
      ITT applicator in order to find optimal laser parameters and damage thresholds.
      The lesions were investigated using macroscopic size measurement, volume
      calculation and histological examination (H&E, NADPH-dehydrogenase). The damage
      threshold of the diffusing tip was 6 W at 14 min exposure time whereas the
      Ringmode((r))-ITT applicator had its limit at 5 W and 12 min exposure. Comparing
      various exposure times showed that treatment over a time of more than 840 s did
      not significantly increase the lesion volume. At 5 W and 720 s the mean lesion
      volume was 6.9+/-1.1 cm(3) with the diffusing tip and 6.3+/-0.6 cm(3) with the
      Ringmode((r))-ITT applicator, both having a slight ellipsoidal shape. Hence, the
      created lesions were not significantly different for both applicators when the
      same laser parameters were applied. On the other hand, the new diffusing tip had
      a higher damage threshold and was therefore capable of producing maximal
      coagulation volumes of up to 7.9+/-0.5 cm(3) at 5 W and 20 min. The experiments
      showed that lesions with a dimension of 31*22 mm can be achieved with the
      diffusing applicator which seem suitably sized for treating small human liver
      metastases in a single laser session. 

PMID- 24584810
TI  - mTHPC Polymer Conjugates: The In Vivo Photodynamic Activity of Four Candidate
      Compounds.
AB  - The in vivo photodynamic activities of four poly(ethylene glycol) (PEG)
      conjugates of the photosensitiser 5,10,15,20-tetrakis-(m-hydroxyphenyl)chlorin
      (mTHPC, temoporfin, Foscan((r))) were compared with that of mTHPC over a range of
      drug-light intervals using acute tumour necrosis and skeletal muscles swelling in
      a mouse model in order to ascertain the influence of linking group stability and
      PEG chain length on the photodynamic activity. The four compounds examined
      contained either PEG 2000 or PEG 5000 attached by carbonate or triazine linkages
      at the phenol hydroxyl groups of the mTHPC.All compounds tested caused tumour
      necrosis at drug-light intervals of between one and four days. mTHPC produced
      tumour necrosis of over 5 mm at drug-light intervals of 1 and 2 days with limited
      muscle damage at early drug-light intervals. The relatively labile carbonate
      linked conjugates gave tumour necrosis similar to mTHPC but produced severe
      muscle and systemic phototoxicity on irradiation at 4-24 h after injection. The
      more stable triazine-linked conjugates produced no significant muscle damage at
      any of the drug-light intervals tested, but gave only limited tumour necrosis
      under the conditions tested. PEG chain length had relatively little effect on the
      patterns of bioactivity.It is concluded that both classes of mTHPC PEG conjugates
      may be suitable for photodynamic therapy if the problems of stability and early
      photosensitivity in the case of the carbonates and reduced potency in the case of
      the triazines can be overcome through improved formulations and PDT treatment
      regimens. 

PMID- 24584811
TI  - Pneumothorax monitoring by remittance measurement: comparison between
      experimental model and animal studies.
AB  - Pneumothorax monitoring by remittance measurement in neonatology is investigated
      using model experiments. The results are compared to previous animal experiments.
      A multifibre probe is used to measure the change in remittance at 632.8 nm and
      790 nm as a function of the thickness of a layer of air between a model chest
      wall (optically matched to piglet chest walls) and a model lung. An increase in
      thickness of this layer of air results in a decrease in remittance. Only when a
      relatively thin model chest wall is used (thickness 4 or 6 mm) and detection
      fibres are at some distance from the source, is this decrease in remittance
      preceded by an initial increase in remittance. Relative changes in remittance are
      larger at 790 nm then at 632.8 nm. The results in general correspond to the
      results of the animal experiments. However, not all results of the animal
      experiments could be explained. We conclude that our assumptions for the model
      experiments did not cover all aspects of the development of a pneumothorax and
      dynamic models with changing optical properties should be used instead. In
      conclusion, the results in general confirm and help understand the results of the
      animal experiments and indicate that pneumothorax monitoring by remittance
      measurement is feasible. 

PMID- 24584812
TI  - Photodynamic inactivation of staphylococci with 5-aminolaevulinic Acid or
      photofrin.
AB  - Widespread use of antibiotics for bacterial infections is a reason for antibiotic
      resistance. Therefore, alternatives like photodynamic therapy (PDT) are studied
      for bacterial eradication.The viability of Staphylococcus (S.) aureus and S.
      epidermidis was studied following photosensitisation with different
      concentrations of 5-aminolevulinic acid (5-ALA) or Photofrin((r)) and irradiation
      with a dye laser. After ALA without irradiation growth of S. epidermidis was
      reduced, surprisingly growth of S. aureus significantly increased. Using ALA and
      light a significant and concentration-dependent decrease of bacterial growth was
      measured in both strains. However, for S. epidermidis there was no difference
      between ALA with or without irradiation. Photofrin without light decreased
      bacterial growth significantly, indicating a high dark toxicity of the drug.
      Photofrin and light lead to a highly significant reduction of growth in both
      strains.While 5-ALA killed only up to 39% of Staphylococci, Photofrin was able to
      eradicate up to 93% of the bacteria. The poor response to 5-ALA may be due to an
      insufficient synthesis of photodynamically active porphyrins in Staphylococci.
      Although topical PDT could be useful for superinfected wounds or leg ulcers, the
      in-vitro bactericidal effect of 5-ALA PDT on staphylococci was not satisfactory. 

PMID- 24584813
TI  - Laser myringotomy (L-myringotomy) and ventilating tubes: a preliminary
      comparative study.
AB  - A prospective comparative study was done to assess the validity of laser
      myringotomy (L-myringotomy) when compared to the insertion of ventilating tubes
      (VT). In 23 children with chronic otitis media with effusion, a VT was inserted
      in the left ear while a laser myringotomy was performed in the right ear by using
      the CO2 Sharplan 1030 laser. After a six month follow-up conducted during the
      winter months, the results with the laser myringotomy were equal to those in the
      left ear with the VT. During the follow-up period, three ears required additional
      laser myringotomy either for early closure or because of otitis media and the
      accumulation of effusion in the middle ear cavity. Nevertheless, the use of laser
      has the advantage that there is no foreign body in the ear, the tympanic membrane
      is closed after four to seven weeks, and since the procedure is very short, the
      time for anaesthesia is minimal. 

PMID- 24584814
TI  - Measurement of the emission profiles of cylindrical light diffusers using a video
      technique.
AB  - The uniformity of the emission profile produced by a cylindrical light diffuser
      is an important parameter for determining the light dose received by the target
      tissue during laser therapies such as photodynamic therapy (PDT) and interstitial
      laser photocoagulation (ILP). A technique originally used for determining the
      profile of a laser beam with a commercial video camera is adapted in order to
      measure the distribution of light from a cylindrical diffuser. The method can
      produce quantitative one-dimensional beam profiles in both the circumferential
      and axial direction of the light diffuser. The system allows the use of tissue
      phantoms that provide a convenient and effective method for comparing
      manufacturer's measurements often made in air with those to be expected in vivo.
      The technique is a quick and easy method for assessing light diffusers before
      treatment, and utilises readily available equipment that does not require
      specialist knowledge. Also, the response of the video camera facilitates the
      assessment of diffusers over a relatively broad optical spectrum, which
      encompasses the range of wavelengths currently used for both PDT (515-675 nm) and
      ILP (800-1064 nm). 

PMID- 24584815
TI  - Disinfection of the Optical Fibre of a Nd-YAP Laser Used in Dental Care.
AB  - In order to set up a disinfection protocol, the tip of the optical fibre of an Nd
      YAP laser, lambda=1.34 MUm, was contaminated in vitro with: Mycobacterium
      smegmatis (CIP 7326), Candida albicans (ATCC 2091), Bacillus stearothermophilus
      (ATCC 7953) or Streptococcus sanguis (ATCC 10556). It was then treated with
      various biocidal solutions, Septinol((r)) V, glutaraldehyde 2%, ethanol 95
      degrees  and NaOCl 6%, using one of two protocols: 10 s of contact, or 5 s of
      contact followed by 5 s of wiping. The latter technique proved to be the most
      effective. Whatever the biocidal solution used, all the bacteria adhering to the
      fibre were eliminated. The protocol was checked in vivo in the canals of 10 teeth
      presenting root canal infections. No bacteria withstood the treatment with
      Septinol((r)) V. This treatment does not alter the qualities and performance of
      the fibre as far as light transmission is concerned. 

PMID- 24584816
TI  - JAM-C promotes lymphangiogenesis and nodal metastasis in non-small cell lung
      cancer.
AB  - This study aims to investigate lymphatic metastasis-related genes in non-small
      cell lung carcinomas (NSCLC). NSCLC tissue was analyzed for expression of
      junctional adhesion molecule-C (JAM-C) protein. Our data revealed novel
      associations between JAM-C overexpression in primary tumors and lymphatic
      microvessel density (LMVD), lymph node metastasis, and poorer overall survival
      and recurrence-free survival. We used the highly metastatic human lung
      adenocarcinoma cell line Anip973 and its parental line AGZY83-a, which has a low
      metastatic capacity, in vivo and vitro. We found that JAM-C played an important
      role in different metastasis capacity of lymph node. JAM-C affected tumor growth,
      LNM, JAM-C, VEGF-C, vasculature, and ERK1/2 phosphorylation (p-ERK1/2). beta1
      integrin was involved in lymph node metastasis. Moreover, JAM-C knockdown in
      highly metastatic Anip973 decreased cell migration in scratch-wound assays. The
      JAM-C knockdown in Anip973 cells and JAM-C cDNA in AGZY83-a cells regulated the
      vascular endothelial growth factor C (VEGF-C) expression. Immunofluorescence
      showed that blocked VEGF-C expression in JAM-C shRNA Anip973 cells were restored
      after JAM-C treatment. JAM-C-induced VEGF-C in JAM-C cDNA AGZY83-a cells was also
      effectively inhibited by treatment with an antibody specifically against JAM-C.
      Use of media from Anip973 cells, AGZY83-a, and A549cells lung cancer cells that
      overexpressed or downregulated JAM-C was demonstrated to affect activity of VEGF
      C-induced beta1 integrin subunit or ERK activity in human dermal lymphatic
      endothelial cells (HDLEC) treated with VEGF-C or inhibitory antibody to JAM-C.
      Overall, these results indicate that JAM-C could mediate metastasis as it
      contributes to VEGF-C expression in cancer cells. JAM-C affects beta1and ERK
      activation in HDLEC, thus promoting lymphangiogenesis and nodal metastasis. Our
      findings indicate that JAM-C may be a therapeutic target for preventing and
      treating lymphatic metastases. 

PMID- 24584818
TI  - Spouse health behavior outcomes from a randomized controlled trial of a spouse
      assisted lifestyle change intervention to improve patient low-density lipoprotein
      cholesterol.
AB  - This study evaluated spouse health behavior outcomes from a randomized controlled
      trial of a spouse-assisted lifestyle intervention to reduce patient low-density
      lipoprotein cholesterol and improve patient health behaviors. Participants were
      251 spouses of patients from the Durham Veterans Affairs Medical Center
      randomized to intervention or usual care. The intervention comprised 9 monthly
      telephone calls to patients and spouses. Outcomes were assessed at baseline, 6
      and 11 months. At 11 months, there were no differences in spouse outcomes between
      intervention and usual care groups for moderate intensity physical activity
      (i.e., frequency, duration) or dietary intake (i.e., total calories, total fat,
      percentage of calories from total fat, saturated fat, percentage of calories from
      saturated fat, cholesterol, fiber). To improve spouse outcomes, couple
      interventions may need to include spouse behavior change goals and reciprocal
      support between patients and spouses and consider the need for improvement in
      spouse outcomes. 

PMID- 24584817
TI  - Decitabine facilitates immune recognition of sarcoma cells by upregulating CT
      antigens, MHC molecules, and ICAM-1.
AB  - Rhabdomyosarcoma, osteosarcoma, and Ewing's sarcoma are the most common types of
      sarcoma in children. Despite standard therapy, nearly one third of the patients
      with Ewing's sarcoma relapse, and there are limited options with curative
      potential. Immunotherapy is a promising approach as it can target tumor-specific
      antigens that are specifically expressed on tumors while sparing non-malignant
      cells. We have demonstrated that a demethylating chemotherapeutic drug, 5-aza-2'
      deoxycytidine (decitabine, DAC) can upregulate the expression of cancer-testis
      (CT) antigens, MHC molecules, and intracellular cell adhesion molecule-1 on
      pediatric sarcoma cell lines, resulting in enhanced killing of tumor cells by CT
      antigen-specific cytotoxic T lymphocytes derived from pediatric sarcoma patients.
      A significant increase in the mRNA expression levels of MAGE-A1 and MAGE-A3 were
      found in 70 %, and NY-ESO-1 in 80 % of the sarcoma lines following exposure to
      pharmacological levels of DAC. The high expression levels of MAGE-A1, MAGE-A3,
      and NY-ESO-1 were sustained in sarcoma lines and primary tumor lines over 30 days
      after the cessation of DAC. Furthermore, DAC treatment induced upregulation of
      MAGE-A1, MAGE-A3, or NY-ESO-1 protein expression in seven of nine lines studied.
      These studies show that demethylating chemotherapy could be combined with CT
      antigen-directed immunotherapy for treating pediatric sarcoma.

PMID- 24584820
TI  - The unfolded protein response is triggered in rat neurons of the dorsal raphe
      nucleus after single-prolonged stress.
AB  - The dorsal raphe nucleus (DRN) has been suggested playing an important role in
      the pathophysiology of post-traumatic stress disorder (PTSD), however the
      underlying cellular mechanisms are not fully understood. The endoplasmic
      reticulum (ER) is a critical organelle for synthesis of membrane and secretory
      proteins, and perturbations in ER lead to the unfolded protein response (UPR). In
      the present experiment, we hypothesized UPR may be associated with the PTSD, and
      there is an induction of UPR in the DRN neurons of the PTSD-like rats. We first
      observed the morphological changes of ER in the DRN neurons of the rats exposed
      to single-prolonged stress (SPS), a model of PTSD, and then we also detected the
      expression of ER chaperones glucose regulated protein 78 (GRP78) and glucose
      regulated protein (GRP94) which are two key sensors and mediators of the UPR and
      are considered an ER stress-specific inducible proteins using methods of western
      blot and immunohistochemical analysis. Our results demonstrated there were
      abnormal expansion of ER and up-regulation expression of GRP78 and GRP94 after
      SPS, which indicated that the UPR was triggered in the DRN neurons of the PTSD
      like rats. These results are consistent with our speculation that UPR may be
      associated with the PTSD, and suggest us the UPR may be a new critical cellular
      mechanisms of PTSD. 

PMID- 24584819
TI  - Subchronic oral administration of Benzo[a]pyrene impairs motor and cognitive
      behavior and modulates S100B levels and MAPKs in rats.
AB  - Benzo[a]pyrene (BaP) is an environmental contaminant produced during incomplete
      combustion of organic material that is well known as a mutagenic and carcinogenic
      toxin. There are few studies addressing the molecular and cellular basis of
      behavioural alterations related to BaP exposure. The aim of this study was to
      evaluate the effect of subchronic oral administration of BaP on behavioral and
      neurochemical parameters. Wistar male rats received BaP (2 mg/kg) or corn oil
      (control), once a day for 28 days (n = 12/group). Spontaneous locomotor activity
      and short- and long-term memories were evaluated. Glial fibrillary acid protein
      and S100B content in the hippocampus, serum and CSF were measured using ELISA and
      total and phosphorylated forms of mitogen activated protein kinases (MAPKs) named
      extracellular signal-regulated kinases 1 and 2, p38(MAPK) and c-Jun amino
      terminal kinases 1 and 2, in the hippocampus, were evaluated by western blotting.
      BaP induced a significant increase on locomotor activity and a decrease in short
      term memory. S100B content was increased significantly in cerebrospinal fluid.
      BaP induced a decrease on ERK2 phosphorylation in the hippocampus. Thus, BaP
      subchronic treatment induces an astroglial response and impairs both motor and
      cognitive behavior, with parallel inhibition of ERK2, a signaling enzyme involved
      in the hippocampal neuroplasticity. All these effects suggest that BaP
      neurotoxicity is a concern for environmental pollution. 

PMID- 24584821
TI  - Binding of Clostridium botulinum C3 exoenzyme to intact cells.
AB  - C3 from Clostridium botulinum (C3) specifically modifies Rho GTPases RhoA, RhoB,
      and RhoC by mono-ADP-ribosylation. The confined substrate profile of C3 is the
      basis for its use as pharmacological tool in cell biology to study cellular
      functions of Rho GTPases. Although C3 exoenzyme does not possess a cell-binding/
      translocation domain, C3 is taken up by intact cells via an unknown mechanism. In
      the present work, binding of C3 to the hippocampus-derived HT22 cells and J774A.1
      macrophages was characterized. C3 bound concentration-dependent to HT22 and
      J774A.1 cells. Pronase treatment of intact cells significantly reduced both C3
      binding and C3 cell entry. Removal of sugar residues by glycosidase F treatment
      resulted in an increased binding of C3, but a reduced cell entry. To explore the
      involvement of phosphorylation in the binding process of C3, intact HT22 and
      J774A.1 cells were pre-treated with vanadate prior to incubation with C3.
      Inhibition of de-phosphorylation by vanadate resulted in an increased binding of
      C3. To differentiate between intracellular and extracellular phosphorylation,
      intact cells were treated with CIP (calf intestine phosphatase) to remove
      extracellular phosphate residues. The removal of phosphate residues resulted in a
      strong reduction in binding of C3 to cells. In sum, the C3 membranous binding
      partner is proteinaceous, and the glycosylation as well as the phosphorylation
      state is critical for efficient binding of C3. 

PMID- 24584822
TI  - Comprehensive evaluation of the incidence of late effects in 5-year survivors of
      breast cancer.
AB  - Late effects of breast cancer affect the quality of survivorship. Using
      administrative data, we compared the occurrence of almost all ICD9 codes among
      older breast cancer survivors to that among a matched comparison cohort to
      generate new hypotheses. Breast cancer patients 65 years or older diagnosed 1990
      1994 in 6 integrated care settings and who survived at least 5 years were matched
      with a cohort of women without a history of breast cancer on care setting, age,
      and calendar time. We collected data on the occurrence of incident ICD9 codes
      beginning 6 years after the breast cancer diagnosis date and continuing to year
      15, and comparable data for the matched woman. We calculated hazard ratios (HRs)
      and 95 % confidence intervals associating breast cancer survivorship with
      incidence of each ICD9 code. We used semi-Bayes methods to address multiple
      comparisons. Older breast cancer survivors had about the same occurrence of
      diseases and conditions 6-15 years after breast cancer diagnosis as comparable
      women. The median of 564 adjusted HRs equaled 1.06, with interquartile range 0.92
      1.3. The distribution of HRs pertaining to cancer-related ICD codes was shifted
      toward positive associations, and the distribution pertaining to cardiovascular
      related ICD codes was shifted toward negative associations. In this hypothesis
      scanning study, we observed little difference in the occurrence of non-breast
      cancer-related diseases and conditions among older, long-term breast cancer
      survivors, and comparable women without a history of breast cancer.

PMID- 24584833
TI  - Translating the power of TCM into patients' hope.

PMID- 24584835
TI  - Pharmacy and public health: a pathway forward.
AB  - OBJECTIVE To identify a pathway forward for practicing pharmacists in supporting
      public health initiatives by applying the five core competencies of public
      health. SUMMARY The pharmacist is well positioned to improve population health.
      Until now, increased impact of pharmacists has been based on the expansion of
      patient services rather than guided by a population approach to health. To
      increase their effectiveness and breadth of impact, pharmacists would benefit
      from applying the five core competencies of public health (social and behavioral
      science, health policy and administration, epidemiology, biostatistics, and
      environmental health sciences) to the practice of pharmacy. This article aims to
      explain how each of the core competencies applies to pharmacy practice and how
      pharmacists might apply public health skills in a more specific manner.
      CONCLUSION With increased clarity of the role of public health, and mastery of
      the five core competencies of public health, pharmacists can make unique and
      valuable contributions to the health of the public. 

PMID- 24584834
TI  - Poly-4-vinylphenol and poly(melamine-co-formaldehyde)-based graphene passivation
      method for flexible, wearable and transparent electronics.
AB  - Next generation graphene-based electronics essentially need a dielectric layer
      with several requirements such as high flexibility, high transparency, and low
      process temperature. Here, we propose and investigate a flexible and transparent
      poly-4-vinylphenol and poly(melamine-co-formaldehyde) (PVP/PMF) insulating layer
      to achieve intrinsic graphene and an excellent gate dielectric layer at sub 200 
      degrees C. Chemical and electrical effects of PVP/PMF layer on graphene as well
      as its dielectric property are systematically investigated through various
      measurements by adjusting the ratio of PVP to PMF and annealing temperature. The
      optimized PVP/PMF insulating layer not only removes the native -OH functional
      groups which work as electron-withdrawing agents on graphene (Dirac point close
      to zero) but also shows an excellent dielectric property (low hysteresis
      voltage). Finally, a flexible, wearable, and transparent (95.8%) graphene
      transistor with Dirac point close to zero is demonstrated on polyethylene
      terephthalate (PET) substrate by exploiting PVP/PMF layer which can be scaled
      down to 20 nm. 

PMID- 24584837
TI  - Pearls and pitfalls on ALPPS procedure: new complications in a new technique.

PMID- 24584836
TI  - An altered spinal serotonergic system contributes to increased thermal
      nociception in an animal model of depression.
AB  - The olfactory bulbectomized (OB) rat, an animal model of chronic depression with
      comorbid anxiety, exhibits a profound dysregulation of the brain serotonergic
      signalling, a neurotransmission system involved in pain transmission and
      modulation. We here report an increased nociceptive response of OB rats in the
      tail flick test which is reverted after chronic, but not acute, administration of
      fluoxetine. Autoradiographic studies demonstrated down-regulation of 5-HT
      transporters ([(3)H]citalopram binding) and decreased functionality of 5-HT1A
      receptors (8-OH-DPAT-stimulated [(35)S]GTPgammaS binding) in the dorsal horn of
      the lumbar spinal cord in OB rats. Acute administration of fluoxetine (5-40 mg/kg
      i.p.) did not modify tail flick latencies in OB rats. However, chronic fluoxetine
      (10 mg/kg/day s.c., 14 days; osmotic minipumps) progressively attenuated OB
      associated thermal hyperalgesia, and a total normalization of the nociceptive
      response was achieved at the end of the treatment with the antidepressant. In
      these animals, autoradiographic studies revealed further down-regulation of 5-HT
      transporters and normalization in the functionality of 5-HT1A receptors on the
      spinal cord. On the other hand, acute morphine (0.5-10 mg/kg s.c.) produced a
      similar analgesic effect in OB and sham and OB rats, and no changes were detected
      in the density ([(3)H]DAMGO binding) and functionality (DAMGO-stimulated
      [(35)S]GTPgammaS binding) of spinal MU-opioid receptors in OB rats before and
      after chronic fluoxetine. Our findings demonstrate the participation of the
      spinal serotonergic system in the increased thermal nociception exhibited by the
      OB rat and the antinociceptive effect of chronic fluoxetine in this animal model
      of depression.

PMID- 24584838
TI  - [Pneumocephalus as a rare complication of general anesthesia].
AB  - This article reports a case of massive postoperative pneumocephalus in a patient
      following general anesthesia for a urological procedure. The patient had
      sustained a severe head injury more than 10 years ago with long-term treatment in
      an intensive care unit (ICU) including decompressive craniectomy, tracheostomy
      followed by rehabilitation, decanulation and cranioplasty. The patient recovered
      but suffered severe hemiparesis and mild neurocognitive deficits. Immediately
      after the current operation the patient was disoriented and did not recover in an
      appropriate interval. A cranial computed tomography (CT) scan revealed massive
      intracranial air and frontobasal skull defects. After frontobasal reconstruction,
      removal of an old lumboperitonal shunt and placement of a ventriculoperitoneal
      shunt, intracranial air was no longer observed. In summary a frontobasal injury
      may become symptomatic many years after injury, especially when face mask
      ventilation with positive pressure is applied during surgical interventions. 

PMID- 24584839
TI  - [Hypoxic gas mixture delivery due to a defective vaporiser manifold: case report,
      review of the literature and suggested emergency management algorithm].
AB  - A case of delivery of a hypoxic gas mixture to a patient during total intravenous
      anesthesia is described. A progressive fall in inspiratory oxygen concentration
      followed by a drop in oxygen saturation below 90 % occurred during the advanced
      stages of a hitherto uneventful general anesthesia of a female patient undergoing
      anterior cervical fusion surgery. A malfunctioning defective rubber seal of a
      vaporizer manifold was identified as the cause of the gas leak. The leak had not
      been detected during the preanesthesia leak test. The problem of hypoxic gas
      mixtures and uncommon leaks in modern anesthesia equipment is discussed. The
      importance of locating a leak in the high or low pressure circuits is explained.
      An algorithm for the management of an unexpected decrease of inspiratory oxygen
      concentration or any other manifestation of a gas leak along with a systematic
      approach to locating the source of a gas leak is presented. 

PMID- 24584841
TI  - Association between IgA deficiency & other autoimmune conditions: a population
      based matched cohort study.
AB  - PURPOSE: To examine autoimmune disorders in patients with IgA deficiency compared
      with the general population. METHODS: Nationwide prospective population-based
      cohort study. Through six university hospitals in Sweden we identified 2100
      individuals with IgA deficiency (IgA levels < .07 g/L) diagnosed between 1980 and
      2011. Each patient with IgA deficiency was matched on age, sex, place of
      residence, and year of diagnosis with up to 10 general population controls (n =
      18,653). Data on nine autoimmune disorders were retrieved from the Swedish
      National Patient Register (including inpatient and non-primary outpatient care).
      Autoimmune disorders were defined as having at least two visits listing the
      relevant international classification of disease (ICD) code as main diagnosis.
      Prevalences and prevalence ratios (PRs) were calculated. RESULTS: Individuals
      with IgA deficiency more often had celiac disease (6.7 % vs. 0.19 % in controls)
      and type 1 diabetes (5.9 % vs. 0.57 %) corresponding to a 35-fold higher PR for
      celiac disease and 10-fold higher for type 1 diabetes. Also for the other
      autoimmune diseases did we see statistically significantly elevated prevalences
      and PRs (juvenile idiopathic arthritis (0.76 % vs. 0.09 % in controls, PR = 8.9),
      systemic lupus erythematosus (0.57 % vs. 0.06 %; PR = 8.9), inflammatory bowel
      disease (3.9 % vs. 0.81 %; PR = 5.0; specifically Crohn's disease (2.4 % vs. 0.42
      %; PR = 5.7) and ulcerative colitis (1.7 % vs. 0.46 %; PR = 3.9)), hypothyreosis
      (0.76 % vs. 0.16 %; PR = 4.6), rheumatoid arthritis (2.2 % vs. 0.50 %; PR = 4.5),
      and hyperthyreosis (1.7 % vs. 0.43 %; PR = 3.9), but not with myasthenia gravis
      (0.05 % vs. 0.02 %; PR = 3.0). CONCLUSIONS: Individuals with IgA deficiency have
      a higher prevalence of several other autoimmune disorders.

PMID- 24584842
TI  - Introduction to travelling president's fellowship.

PMID- 24584840
TI  - [Interaction of anesthetics and analgesics with tumor cells].
AB  - The results of preclinical and clinical studies indicate that the perioperative
      period is a vulnerable period for cancer progression and metastasis. The risk of
      cancer cell dissemination is enhanced by the combination of surgical manipulation
      and perioperative immunosuppression. Whether the oncological outcome of cancer
      patients can be influenced by the choice of anesthetic techniques is still a
      matter of debate. This review summarizes the molecular characteristics of cancer
      and interaction of anesthetic and analgesic drugs with cancer cells. 

PMID- 24584843
TI  - Farnesol induces apoptosis of DU145 prostate cancer cells through the PI3K/Akt
      and MAPK pathways.
AB  - The aim of this study was to investigate the effect of farnesol on the induction
      of apoptosis in DU145 prostate cancer cells. 3-(4,5-Dimethylthiazol-2-yl)-2,5
      diphenyl tetrazolium bromide assay showed that cell proliferation decreased
      significantly in a dose- and time-dependent manner. 4',6-Diamidino-2-phenylindole
      staining showed that chromatin condensation in cells treated with 60 uM of
      farnesol was markedly higher than in the control groups. Farnesol increased the
      expression of p53, p-c-Jun N-terminal kinase, cleaved-caspase-3, Bax, and cleaved
      caspase-9, but decreased the expression of p-phosphatidylinositol-3-kinase
      (PI3K), p-Akt, p-p38, Bcl-2, and p-extracellular signal-regulated protein kinase,
      in a dose-dependent manner. The apoptotic cell ratio increased in a dose
      dependent manner. The tumor growth inhibitory effect of farnesol was investigated
      in a mouse model. Compared to the control group, tumor volume decreased
      significantly in the group administered 50 mg/kg farnesol. Apoptosis was
      frequently detected in this same group by terminal deoxynucleotidyl transferase
      dUTP nick-end labeling assay. The results indicated that farnesol induced
      apoptosis of DU145 prostate cancer cells through the PI3K/Akt and mitogen
      activated protein kinase signaling pathways.

PMID- 24584844
TI  - Holmium:YAG laser bronchoscopy ablation of benign and malignant airway
      obstructions: an 8-year experience.
AB  - Patients suffering from severe tracheobronchial obstruction are vulnerable to
      dyspnea, respiratory failure, obstructive pneumonia, and death. Treatment with a
      holmium:YAG laser, an alternative to the neodymium:YAG laser, may provide
      symptomatic relief. This is the largest case series to date describing the
      application of the holmium:YAG laser via bronchoscopy for benign and malignant
      obstructive disease. The data were retrospectively collected from 99 patients,
      with either benign or malignant tracheobronchial obstruction, who underwent 261
      interventional bronchoscopy procedures in the operating room with laser ablation
      between January 2004 and November 2011. Categorical variables were analyzed with
      the chi-square and Fisher's exact tests as appropriate in contingency tables,
      whereas Student's t-test was performed for comparison of continuous variables.
      Patient follow-up was concluded on September 15, 2013. The holmium:YAG laser was
      used in 261 procedures performed on 99 patients with either benign or malignant
      disease. Symptomatic improvement was demonstrated in 90 % of all benign etiology
      cases and 77 % of all malignant etiology cases. Within the benign and malignant
      subgroups, improvement was dependent on anatomical location rather than etiology
      of the lesion. Complications occurred in 2.3 % of the procedures, with mortality
      in less than 1 % of procedures. Results confirm the usefulness and safety of the
      holmium:YAG laser in the treatment of patients with severe benign and malignant
      obstructive tracheobronchial obstructions. The holmium:YAG laser is an appealing
      alternative to the neodymium:YAG laser.

PMID- 24584845
TI  - Characterization and expression patterns of small RNAs in synthesized Brassica
      hexaploids.
AB  - Polyploidy has played an important role in promoting plant evolution through
      genomic merging and doubling. We used high-throughput sequencing to compare miRNA
      expression profiles between Brassica hexaploid and its parents. A total of 613,
      784 and 742 known miRNAs were identified in Brassica rapa, Brassica carinata, and
      Brassica hexaploid, respectively. We detected 618 miRNAs were differentially
      expressed (log(2)Ratio >= 1, P <= 0.05) between Brassica hexaploid and its
      parents, and 425 miRNAs were non-additively expressed in Brassica hexaploid,
      which suggest a trend of non-additive miRNA regulation following hybridization
      and polyploidization. Remarkably, majority of the non-additively expressed miRNAs
      in the Brassica hexaploid are repressed, and there was a bias toward repression
      of B. rapa miRNAs, which is consistent with the progenitor-biased gene repression
      in the synthetic allopolyploids. In addition, we identified 653 novel mature
      miRNAs in Brassica hexaploid and its parents. Finally, we found that almost all
      the non-additive accumulation of siRNA clusters exhibited a low-parent pattern in
      Brassica hexaploid. Non-additive small RNA regulation is involved in a range of
      biological pathways, probably providing a driving force for variation and
      adaptation in allopolyploids.

PMID- 24584846
TI  - Asp120Asn mutation impairs the catalytic activity of NDM-1 metallo-beta
      lactamase: experimental and computational study.
AB  - New Delhi metallo-beta-lactamase-1 (NDM-1) has attracted extensive attention in
      recent years for its high activity for hydrolyzing almost all beta-lactam
      antibiotics. Like other metallo-beta-lactamases (MbetaLs), NDM-1 features an
      invariant Asp120 that ligates the zinc ion (ZN2) in the active site. Previous
      studies showed that substitutions of Asp120 with residues such as Ala, Ser, Asn
      and Glu dramatically impaired the MbetaL (BcII, IMP-1, L1) activity, but no
      consensus about the exact role of Asp120 has reached. Here we constructed D120N
      mutant of NDM-1 by site-directed mutagenesis. The replacement of Asp120 with Asn,
      which has much weaker metal ligating capabilities than Asp, severely impaired the
      lactamase activity without abolishing the ZN2 site. Molecular dynamics
      simulations suggested that the ZN1-ZN2 distance increased because of mutation,
      leading to a rearrangement of the active site, including the bridging OH(-).
      Thereby, the Mulliken charges of ZN1 and ZN2 redistributed, especially for ZN2,
      which might be the major cause of the impaired activity. Reducing the point
      charges of Asp120 carboxyl oxygens weakened the ionic interactions between Asp120
      and ZN2, and the positions of the zinc ions were also changed as a result. It is
      proposed that Asp120 acts as a strong ZN2 ligand, positioning ZN2 for
      catalytically important interactions with the substrate, stabilizing the
      negatively charged amide nitrogen of the hydrolyzed intermediate, and more
      importantly, orienting the ZN-bound OH(-) for nucleophilic attacks and
      protonation. These functions are of general importance for catalyzing beta-lactam
      antibiotics by NDM-1 as well as other MbetaLs. 

PMID- 24584857
TI  - CEBPA-dependent HK3 and KLF5 expression in primary AML and during AML
      differentiation.
AB  - The basic leucine zipper transcription factor CCAAT/enhancer binding protein
      alpha (CEBPA) codes for a critical regulator during neutrophil differentiation.
      Aberrant expression or function of this protein contributes to the development of
      acute myeloid leukemia (AML). In this study, we identified two novel unrelated
      CEBPA target genes, the glycolytic enzyme hexokinase 3 (HK3) and the kruppel-like
      factor 5 (KLF5) transcription factor, by comparing gene profiles in two cohorts
      of CEBPA wild-type and mutant AML patients. In addition, we found CEBPA-dependent
      activation of HK3 and KLF5 transcription during all-trans retinoic acid (ATRA)
      mediated neutrophil differentiation of acute promyelocytic leukemia (APL) cells.
      Moreover, we observed direct regulation of HK3 by CEBPA, whereas our data suggest
      an indirect regulation of KLF5 by this transcription factor. Altogether, our data
      provide an explanation for low HK3 and KLF5 expression in particular AML subtype
      and establish these genes as novel CEBPA targets during neutrophil
      differentiation. 

PMID- 24584858
TI  - Mycobacterium tuberculosis silicone gluteus abscesses with bone involvement.

PMID- 24584859
TI  - An easy way for congenital symmastia correction.
AB  - Congenital symmastia is described as a connection between the breasts without
      macromastia. In this condition, there is accumulation of fat and glandular tissue
      between the breasts, which produces a unified appearance of the breast tissue
      across the chest. We report a case of congenital symmastia in a 21-year-old woman
      with normal-sized and -shaped breasts. We achieved satisfying aesthetic results
      using suction-assisted lipectomy and the patient's complaint was resolved without
      scar or major surgery. 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- 24584860
TI  - Immediate debridement of road rash injuries with Versajet(r) hydrosurgery:
      traumatic tattoo prevention?
AB  - Traumatic tattoos can result from accidental deposition of foreign particles in
      the dermis. These pigmented particles become permanently lodged in the dermis
      after re-epithelialization of the wound and can give rise to irregular black or
      blue discoloration of the skin. Different methods for tattoo removal exist. The
      best strategy is to prevent traumatic tattooing by immediate removal of the
      foreign bodies before the healing process has begun. We present a fine-tuned
      debridement method to selectively debride the wound and preserve as much viable
      tissue as possible. 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- 24584861
TI  - Utilization of salt whey from Egyptian Ras (cephalotyre) cheese in microbial milk
      clotting enzymes production.
AB  - BACKGROUND: Microbial milk-clotting enzymes are valued as calf rennet substitutes
      in the cheese industry. The worldwide increase of cheese production coupled with
      a reduced supply of calf rennet has prompted a search for calf rennet
      substitutes, including microbial and plant rennets. However, most plant rennets
      have proved unsuitable because they impart a bitter taste to the cheese.
      Microbial rennet appears to be more promising because its production is cheaper,
      biochemical diversity is greater, and genetic modification is easier. Most cheese
      manufacturing facilities in Egypt perform land spreading of salt whey. However,
      this practice increases the chloride levels of soil, and elevates the risk of
      crop damage. One possible application for salt whey is to use it as a whole
      medium for growth and production of milk clotting enzyme from fungi. MATERIAL AND
      METHODS: Mucor pusillus QM 436 was identified to produce the highest milk
      clotting activity during screening of 19 fungal strains. Salted whey results from
      Ras (Cephalotyre) cheese manufacture as a whole medium for growth of Mucor
      pusillus QM 436 and production of the enzyme. RESULTS: The milk-clotting enzyme
      from Mucor pusillus QM 436 was purified to 7.14-fold with 54.4% recovery by
      precipitation in ammonium sulfate, ethanol and fractionated by gel filtration on
      Sephadex G-100. The enzyme was active in the pH range 5.5-7.5 and was inactivated
      completely by heating 5 min at 70 degrees C and 30 min at 65 degrees C. The
      highest level of enzyme activity was obtained at 60 degrees C, pH 5.5. A positive
      and proportional relationship occurred in the presence of CaCl2 in milk, with
      inhibition which occurred in the presence of NaCl. CONCLUSIONS: The high level of
      milk-clotting activity coupled with a low level of thermal stability suggested
      that the milk-clotting enzyme from Mucor pusillus QM 436 should be considered as
      a potential substitute for calf rennet.

PMID- 24584862
TI  - Effects of preparation methods on protein and amino acid contents of various eggs
      available in Malaysian local markets.
AB  - BACKGROUND: The effect of preparation methods (raw, half-boiled and hard-boiled)
      on protein and amino acid contents, as well as the protein quality (amino acid
      score) of regular, kampung and nutrient enriched Malaysian eggs was investigated.
      METHODS: The protein content was determined using a semi-micro Kjeldahl method
      whereas the amino acid composition was determined using HPLC. RESULTS: The
      protein content of raw regular, kampung and nutrient enriched eggs were 49.9 +/
      0.2%, 55.8 +/-0.2% and 56.5 +/-0.5%, respectively. The protein content of hard
      boiled eggs of regular, kampung and nutrient enriched eggs was 56.8 +/-0.1%, 54.7
      +/-0.1%, and 53.7 +/-0.5%, while that for half-boiled eggs of regular, kampung
      and nutrient enriched eggs was 54.7 +/-0.6%, 53.4 +/-0.4%, and 55.1 +/-0.7%,
      respectively. There were significant differences (p < 0.05) in protein and amino
      acid contents of half-boiled, hard-boiled as compared with raw samples, and
      valine was found as the limiting amino acid. It was found that there were
      significant differences (p < 0.05) of total amino score in regular, kampung and
      nutrient enriched eggs after heat treatments.Furthermore, hard-boiling (100
      degrees C) for 10 minutes and half-boiling (100 degrees C) for 5 minutes affects
      the total amino score, which in turn alter the protein quality of the egg.

PMID- 24584863
TI  - Impact of water extracts of Spirulina (WES) on bacteria, yeasts and molds.
AB  - BACKGROUND: Due to its chemical composition, Spirulina is widely used as a
      dietary supplement that exerts positive effects on the human body. It also has
      the ability to inhibit the growth of certain microorganisms, both pathogens that
      pose a health hazard, as well as those that cause food spoilage in all branches
      of food industry. The main aim of this study was to determine the impact of water
      extracts of Spirulina (WES) on the growth of various microorganism both useful
      and harmful for humans and the economy. MATERIAL AND METHODS: The impact of
      different WES concentrations (0.1, 1.0, 2.5, or 5.0%) on the growth of various
      bacteria, yeasts and molds was determined by diffusion method on solid medium.
      RESULTS: It was demonstrated that WES have a diversified impact on
      microorganisms, depending on the species. The inhibitory activity was shown
      against Bacillus subtilis, Micrococcus luteus, Rhodotorula, and Penicillium. WES
      had strong stimulating effect on Alicyclobacillus acidoterrestris and Geotrichum.
      Moreover, higher concentrations of WES stimulated also the development of
      mycelium and production of conidiophores by Cladosporium and Aspergillus niger.
      CONCLUSIONS: Inhibitory impact of WES on microorganisms that cause food spoilage
      may be used in food production. However, the obtained results indicate the need
      for further studies, particularly in order to evaluate the effect of the WES on
      microflora in the food matrices.

PMID- 24584864
TI  - Sensory quality of selected raw ripened meat products.
AB  - BACKGROUND: A demand on raw fermented meat products depends on their
      availability, price and the culture. In Poland, raw meat products have a several
      hundred years, although limited to the Podlasie region, tradition of
      manufacturing. Therefore, in spite of widening of Italian, Spanish, Portuguese,
      German and recently even the Czech Republic products assortment on the Polish
      market, the consumption of them increases slowly. The aim of the study was to
      compare the sensory quality of raw ripened smoked products and sausages, sold on
      the Polish foodstuffs market as "traditional". MATERIAL AND METHODS: The study
      included the basic chemical content, water activity, pH, the amount of lactic
      acid bacteria and coagulase-negative cocci, as well as selected texture and
      sensory parameters. The analysis was conducted in compliance with Polish
      Standards, and the cutting strength was measured with the use of the TA-XT2
      texture-meter. The sensory analysis was conducted by a 12-person panel using the
      5-point method. RESULTS: The differences in the amount of water, protein, fat and
      salt resulted from the wide variability of ingredients among both groups of the
      analysed cold meats. The smoked products were characterised by a higher pH (5.6
      5.9), smaller amount of bacilli (2-5.5 log cfu/g) and lactic cocci (3.3 to 6.6
      log cfu/g) in comparison with the sausages. The amount of both populations of
      bacteria in the sausages of a pH of 4.5-5.5 ranged from 6.8-8.9 log cfu/g and 5.9
      7.7 log cfu/g, respectively. Among the analysed smoked products and sausages the
      greatest TPA hardness (respectively 128.6-140.3 N and 91.3-139.7 N), TPA
      chewiness (28.9-54.2 N and 16.1-36.0 N) and cutting strength (11.0-12.9 kG and
      8.2-8.5 kG) was observed in those with a 0.81-0.86 water activity. The overall
      quality of the analysed cold meats was at a good level (3.9-4.1 pt). CONCLUSIONS:
      Distinguishing features which determined the quality of products are hardness,
      juiciness as well as odour. The specific odour of the yeast cultures present on
      the surface of the products, the high fat content which undergoes oxidation
      during ripening, a high salt content, the domination of pepper among the range of
      spices as well as the detection of lactic and acetic acid are not accepted by
      Polish consumers.

PMID- 24584865
TI  - Applicability of physico-chemical parameters of honey for identification of the
      botanical origin.
AB  - BACKGROUND: Efforts are being made to apply physicochemical parameters analysis
      in the identification of varietal honeys. With many variables describing a given
      population, it is feasible to differentiate between basing on principal component
      analysis (PCA). The aim of this study was to investigate selected physicochemical
      quality characteristics of nectar honey, with particular emphasis paid to
      carbohydrate composition, and to determine its applicability in identifying the
      variety of floral honey. MATERIAL AND METHODS: The experimental materials were
      samples of commercial honey available at retail in Krakow in 2005-2007 period.
      The following analyses were performed: water content by the refractometric
      method, sugars content according to Luff-Schoorl, content of sugars using HPLC,
      electrical conductivity, specific rotation, and acidity of honey. RESULTS:
      Application of HPLC allowed the precise qualitative identification of sugars,
      which was impossible to be determined by Luff-Schoorl method. The obtained
      results were analysed using principal component analysis (PCA). CONCLUSIONS:
      Based on the obtained results and performing the statistical analysis, it was
      found that the relationship between specific rotation and the total acidity can
      be used to distinguish buckwheat honeys from other analysed varieties. Moreover,
      it was demonstrated that the relationship between the specific rotation and
      maltose content can be used to distinguish between acacia honeys vs. buckwheat
      and lime honeys.

PMID- 24584866
TI  - An in-depth review on the medicinal flora Rosmarinus officinalis (Lamiaceae).
AB  - Rosmarinus officinalis (Rosemary) is a common household plant which belongs to
      the family Lamiaceae and is grown in many parts of the world. It is a woody,
      perennial herb with fragrant, evergreen, needle-like leaves and white, pink,
      purple or blue flowers. The two most commonly grown hardy Rosemaries are
      Rosmarinus officinalis 'Arp' and R. officinalis 'Madelene Hill' (syn. 'Hill
      Hardy'). The other cultivars of the plant are R. officinalis 'Albus', R.
      officinalis 'Bendenen Blue', R. officinalis 'Goodwin Creek', R. officinalis 'Herb
      Cottage', R. officinalis 'Logee's Light Blue', R. officinalis 'Miss Jessup's
      Upright', R. officinalis 'Russian River', R. officinalis 'Salem'. The chemical
      constituents include bitter principle, resin, tannic acid, volatile oils and fl
      avonoids. The volatile oil consists of borneol, bornyl acetate, camphene, cineol,
      pinene and camphor. It is used for problems involved in central nervous system,
      cardio vascular system, genito urinary conditions, liver treatments, reproductive
      system and respiratory system. The volatile oil of the plant is used in oils and
      lotions for the treatment of various ailments like arthritis, gout, muscular
      pain, neuralgia, wound and rubbed into hair for stimulating the hair bulbs to
      renewed activity, to prevent premature baldness.

PMID- 24584867
TI  - Evaluation of the content and the potential bioavailability of minerals from
      gluten-free products.
AB  - INTRODUCTION: Gluten-free products usually contain low amounts of protein and
      minerals. However, the information about their nutritional quality is limited.
      The objective of this study was to determine the content and release of minerals
      from selected gluten-free products. MATERIAL AND METHODS: The content and release
      of Ca, Mg, Fe, Zn and Cu from selected gluten-free products was determined. The
      samples were subjected to enzymatic digestion under in vitro conditions. The
      content of minerals in samples before and after enzymatic digestion was
      determined by the fl ame atomic absorption spectrometry. RESULTS: The content of
      minerals varied considerably among the types of foods. The amount of calcium in
      gluten-free products ranged (mg/100 g d.w.) from 3 in corn porridge to 45 in peas
      puff, magnesium: from 13 in peas puff to 33 in corn porridge, iron: from 1.1 in
      bread to 2.6 in pasta, zinc: from 0.8 in biscuits to 6.3 peas puff and copper:
      from 0.07 in bread to 0.4 in pasta. Among analysed products the significant
      higher release of calcium (~68%) and zinc (~62%) was found in corn porridge. The
      highest potential bioavailability for magnesium (~54%) in peas puff, for iron
      (~58%) in biscuits and for copper (~63%) in bread was observed. The relative low
      bioavailability of minerals was found in pasta (from 7% for Ca to 27% for Fe).
      CONCLUSIONS: The content and amount of released minerals from gluten-free
      products are relatively low. The release of minerals from gluten-free products
      depends on the element and composition of the analysed product.

PMID- 24584868
TI  - Assessing the effect, on animal model, of mixture of food additives, on the water
      balance.
AB  - PURPOSE: The purpose of this study was to determine, on the animal model, the
      effect of modification of diet composition and administration of selected food
      additives on water balance in the body. MATERIAL AND METHODS: The study was
      conducted with 48 males and 48 females (separately for each sex) of Wistar strain
      rats divided into four groups. For drinking, the animals from groups I and III
      were receiving water, whereas the animals from groups II and IV were administered
      5 ml of a solution of selected food additives (potassium nitrate - E 252, sodium
      nitrite - E 250, benzoic acid - E 210, sorbic acid - E 200, and monosodium
      glutamate - E 621). Doses of the administered food additives were computed taking
      into account the average intake by men, expressed per body mass unit. Having
      drunk the solution, the animals were provided water for drinking. RESULTS: The
      mixture of selected food additives applied in the experiment was found to
      facilitate water retention in the body both in the case of both male and female
      rats, and differences observed between the volume of ingested fluids and the
      volume of excreted urine were statistically significant in the animals fed the
      basal diet. The type of feed mixture provided to the animals affected the site of
      water retention - in the case of animals receiving the basal diet analyses
      demonstrated a significant increase in water content in the liver tissue, whereas
      in the animals fed the modified diet water was observed to accumulate in the
      vascular bed. CONCLUSION: Taking into account the fact of water retention in the
      vascular bed, the effects of food additives intake may be more adverse in the
      case of females.

PMID- 24584869
TI  - Influence of diet with kale on lipid peroxides and malondialdehyde levels in
      blood serum of laboratory rats over intoxication with paraquat.
AB  - BACKGROUND: Organism's lipid peroxidation is one of the most often examined and
      known physiological process evoked by free radicals. It concerns oxidation
      reaction of unsaturated fatty acid and/or other lipids leading to lipid oxidation
      products (LOP), which as a result of further changes generate among others the
      malondialdehyde molecules. The aim of the work was an estimation if raw or cooked
      kale addition to rat's diet influences antioxidant defense efficiency in their
      organisms in comparison to rats fed with standard AIN-93G diet. MATERIAL AND
      METHODS: The experiment was conducted with 36 Wistar strain, male rats over 21
      days. The rats were divided into 3 groups (each 12 stuck) which were fed with:
      standard diet AIN-93G (2 groups), AIN-93G diet with 10% addition of raw kale (2
      groups), and AIN-93G with 10% addition of cooked lyophilised kale. The total
      content of polyphenols (FC method) and antioxidant activity (ABTS+*) were
      previously determined in raw and then in cooked kale. On the 20th day of
      experiment, half of rats (6 stuck) of each kind of the diet were injected
      intraperitoneally by the solution of paraquat (PQ) in physiological salt to evoke
      the oxidative stress. The next day animals were stunned and blood from their
      hearts was sampled. In the obtained serum, the levels of lipid oxidation products
      (LOP) and malondialdehyde (MDA) were assessed. RESULTS: It was observed that in
      blood serum of rats fed with modified diet with raw and cooked lyophilised kale
      addition the lipid oxides level was lower in comparison to control group fed with
      standard diet (p < 0.05). It was found that intoxication with paraquat caused
      growth of MDA and LOP levels in blood serum of all rats in comparison to not
      intoxicated groups but that growth was the lowest in group fed diet with cooked
      kale addition. CONCLUSION: Diet with kale, both raw and cooked, efficiently
      inhibited the lipid peroxidation process in rats' organisms, ongoing during
      natural metabolism and during evoked oxidative stress.

PMID- 24584870
TI  - Peptides, specific proteolysis products, as molecular markers of allergenic
      proteins - in silico studies.
AB  - The objective of this study was to analyse allergenic proteins by identifying
      their molecular biomarkers for detection in food using bioinformatics tools. The
      protein and epitope sequences were from BIOPEP database, proteolysis was
      simulated using BIOPEP program and UniProt database screening via BLAST and FASTA
      programs. The biomarkers of food proteins were proposed: for example for whey
      proteins - TPEVDDEALEKFDKALKALPMHIR (beta-Lg: fragment 141-164), chicken egg -
      AAVSVDCSEYPKPDCTAEDRPL (ovomucoid: 156-177), wheat -
      KCNGTVEQVESIVNTLNAGQIASTDVVEVVVSPPY (triose phosphate isomerase: 12-46) and
      peanuts - QARQLKNNNPFKFFVPPFQQSPRAVA (arachin: 505-530). The results are
      annotated in the BIOPEP database of allergenic proteins and epitopes, available
      at http://www.uwm.edu.pl/biochemia. The epitope-receptor interactions are
      attributed to the epitope's sequence and suggest that in silico proteolysis
      products showing the highest degree of sequence identity with an epitope or its
      part are characteristic of a given protein or a group of cross-reactive homologs.
      The protein markers from basic food groups were proposed based on the above
      assumption. 

PMID- 24584871
TI  - Nutritive and health-promoting value of organic vegetables.
AB  - In recent years in Poland we may observe a considerable development of organic
      vegetable production. Increased interest in organic products results from an
      opinion of the consumers on their high quality and health safety. However,
      results of research comparing nutritive value and contents of biologically active
      compounds in vegetables from organic and conventional farms are ambiguous. Most
      studies confirm higher contents of certain vitamins and antioxidants in organic
      vegetables, as well as their lower contents of nitrates and pesticide residue in
      comparison to vegetables grown in the conventional manner. There are also reports
      which did not confirm such differences or showed opposite trends. Research
      results at present do not make it possible to formulate a general conclusion on a
      higher health-promoting value of organic vegetables in comparison to those grown
      by conventional farming methods. It is necessary to continue research in order to
      explain the effect of organic raw materials on human health in a more
      comprehensive manner.

PMID- 24584872
TI  - Limited value of the international staging system for predicting long-term
      outcome of transplant-ineligible, newly diagnosed, symptomatic multiple myeloma
      in the era of novel agents.
AB  - We retrospectively investigated clinical outcomes and prognostic factors of 131
      patients with transplant-ineligible newly diagnosed multiple myeloma (NDMM) who
      received melphalan and prednisolone (MP) as first-line therapy from 2006 to 2013.
      Eighty-one patients received salvage therapies incorporating bortezomib,
      lenalidomide, and/or thalidomide. The overall response rate to MP was 54.2 %,
      including 9.2 % of better than very good partial response. With a median follow
      up period of 30.2 months, median overall survival (OS) and median time to next
      treatment (TNT) were 54.4 and 19.0 months, respectively. Univariate analysis
      revealed that performance status and serum calcium level significantly associated
      with both OS and TNT, and multivariate analysis revealed that the higher serum
      calcium level had a significantly unfavorable impact on OS and TNT. Importantly,
      staging informed by the international staging system (ISS) was not predictive for
      OS or TNT in the analyzed cohort. Our study revealed that, in the context of
      first-line MP therapy for NDMM, the salvage therapy incorporating novel agents
      produced a survival period of >30 months after the initiation of second-line
      therapy, suggesting that the predictive value of ISS for OS and TNT may be
      limited in the era of novel agents.

PMID- 24584873
TI  - Primary B-cell CNS lymphoma clinicopathologic and treatment outcomes in 89
      patients from a single tertiary care center.
AB  - Primary central nervous system lymphoma (PCNSL) is a rare aggressive variant of
      diffuse large B-cell lymphoma with a poor prognosis and no defined optimal
      therapeutic strategies. Our aim was to compare the role of intrathecal
      chemotherapy with current high-dose methotrexate (HDMTX) treatments.
      Clinicopathologic characteristics, therapy, and outcomes of patients with PCNSL
      at Moffitt Cancer Center were reviewed in 89 patients identified over an 11-year
      period. Patients treated initially with HDMTX-based therapy showed improved
      overall and progression-free survival, with no improvement shown with added
      radiation or intrathecal therapy. Age and performance status were also important
      prognostic indicators. Our conclusion is that initial therapy in PCNSL should
      include an HDMTX backbone. The use of intrathecal chemotherapy or radiation
      therapy initially likely does not improve outcomes. Future multicenter phase III
      clinical trials are needed to better establish the superior initial treatment in
      PCNSL. 

PMID- 24584874
TI  - Ethylenediaminetetraacetate-dependent pseudothrombocytopenia accompanied by
      morphological changes.

PMID- 24584875
TI  - Application of a decision analytic framework for adoption of clinical trial
      results: are the data regarding TARGIT-A IORT ready for prime time?
AB  - The results from randomized clinical trials are often adopted slowly. This
      practice potentially prevents many people from benefiting from more effective
      care. Provide a framework for analyzing clinical trial results to determine
      whether and when early adoption of novel interventions is appropriate. The
      framework includes the evaluation of three components: confidence in trial
      results, impact of early, and late adoption if trial results are reversed or
      sustained. The adverse impact of early adoption, and the opportunity cost of late
      adoption are determined using Markov modeling to simulate the impact of early and
      late adoption in terms of quality of life years and resources gained or lost. We
      applied the framework to the TARGIT-A randomized clinical trial comparing
      intraoperative radiation (IORT) to standard external beam radiation (EBRT) and
      considered these results in the context of trials comparing endocrine therapy
      with and without radiation therapy in postmenopausal women. Confidence in the
      TARGIT-A trial 4 year results is high because the peak hazard for local
      recurrence in the trial is between 2 and 3 years. This is consistent with most
      trials, and no second peak has been observed in similar patient populations,
      suggesting that the TARGIT-A trial results are stable. The interventions offer
      approximately equivalent life expectancy. If IORT local recurrences rate were as
      high as 10 % at 10 years (which is higher than expected), we would project only
      0.002 fewer expected life years (less than 1 day) compared to EBRT if IORT is
      adopted early. However, there is a $1.7 billion opportunity cost of waiting an
      additional 5 years to adopt IORT in low risk, hormone-receptor-positive,
      postmenopausal women. EBRT costs an additional $1467 in indirect costs per
      patient. Applying an evaluative framework for the adoption of clinical trial
      results to the TARGIT-A IORT therapy trial results in the assessment that the
      trial results are stable, early adoption would lead to minimal adverse impact,
      and substantially less resource use. Both IORT and no radiation are reasonable
      strategies to adopt.

PMID- 24584886
TI  - Erasable thin-film optical diode based on a photoresponsive liquid crystal
      polymer.
AB  - We report a thin-film optical diode written into thin films of a liquid
      crystalline polymer (LCP), which is based on the photoinduced LC-to-isotropic
      phase transition of LCPs. The interference pattern between a collimated and a
      focused UV laser beam is imprinted as chirped volume-phase gratings in
      photoresponsive LCP films and no further processing steps like development or
      liftoff are required for the fabrication. The resultant thin-film device not only
      possesses the fundamental functions of an optical lens for laser beam focusing,
      but also shows diode effects with the focusing/defocusing function dependent on
      the direction of light incidence and orientation of the device. Furthermore, this
      photonic thin-film lens exhibits a spatially tunable spectroscopic response,
      revealing a unique physics of secondary excitations of resonance modes of the
      single-layer LCP waveguide grating structures. This reveals the mechanisms for
      the focusing/defocusing of laser beams by chirped grating structures. Erasability
      and reconstructibility of the photoresponsive LCPs guarantee rewritability of the
      thin-film diode lens. 

PMID- 24584876
TI  - Biomarker prediction of chemotherapy-related amenorrhea in premenopausal women
      with breast cancer participating in E5103.
AB  - This study aimed to investigate whether pre-chemotherapy anti-mullerian hormone
      (AMH) is a biomarker for chemotherapy-related amenorrhea (CRA) in breast cancer
      patients. A multicenter randomized controlled trial, ECOG5103, assigned patients
      with early stage breast cancer to standard doxorubicin-cyclophosphamide followed
      by paclitaxel with either placebo or one of two durations of bevacizumab therapy.
      Five hundred ninety-one patients were part of the decision-making/quality of life
      substudy, in which there were surveys from baseline through 18-month follow-up.
      One hundred twenty-four women were included in this analysis of menses data
      because they were premenopausal at enrollment, responded to the 12-month survey,
      had not undergone bilateral oophorectomy or ovarian function suppression before
      that survey, and had serum banked for research before chemotherapy. One hundred
      of the 124 also responded to the 18-month survey. Median age was 45 years (range
      25-55), and median serum AMH level was 0.11 ng/mL (range 0.01-8.63) prior to
      treatment. Eighty-two percent had CRA at 12 months, and 81 % at 18 months. In
      multivariate analyses, older age (p = 0.0003) was the only statistically
      significant predictor of 12-month CRA, but at 18-months, lower pre-chemotherapy
      AMH (p = 0.04) and older age (p = 0.008) were both statistically significant
      predictors of CRA. Race, bevacizumab therapy, and tamoxifen use were not
      statistically significantly associated with CRA after adjustment for AMH and age.
      Pre-chemotherapy AMH level is a potential novel biomarker for CRA in
      premenopausal women with early stage breast cancer. Further research to evaluate
      the clinical utility of AMH testing is warranted.

PMID- 24584887
TI  - Shift work, long working hours and preterm birth: a systematic review and meta
      analysis.
AB  - PURPOSE: Specific physical activities or working conditions are suspected for
      increasing the risk of preterm birth (PTB). The aim of this meta-analysis is to
      review and summarize the pre-existing evidence on the effect of shift work or
      long working hours on the risk of PTB. METHODS: We conducted a systematic search
      in MEDLINE and EMBASE (1990-2013) for observational and intervention studies with
      original data. We only included articles that met our specific criteria for
      language, exposure, outcome, data collection and original data that were of at
      least of moderate quality. The data of the included studies were pooled. RESULTS:
      Eight high-quality studies and eight moderate-quality studies were included in
      the meta-analysis. In these studies, no clear or statistically significant
      relationship between shift work and PTB was found. The summary estimate OR for
      performing shift work during pregnancy and the risk of PTB were 1.04 (95% CI 0.90
      1.20). For long working hours during pregnancy, the summary estimate OR was 1.25
      (95% CI 1.01-1.54), indicating a marginally statistically significant
      relationship but an only slightly elevated risk. CONCLUSION: Although in many of
      the included studies a positive association between long working hours and PTB
      was seen this did reach only marginal statistical significance. In the studies
      included in this review, working in shifts or in night shifts during pregnancy
      was not significantly associated with an increased risk for PTB. For both risk
      factors, due to the lack of high-quality studies focusing on the risks per
      trimester, in particular the third trimester, a firm conclusion about an
      association cannot be stated.

PMID- 24584885
TI  - [Management of postpartum hemorrhage (PPH): algorithm of the interdisciplinary D
      A-CH consensus group PPH (Germany - Austria - Switzerland)].
AB  - Postpartum hemorrhage (PPH) is one of the main causes of maternal deaths even in
      industrialized countries. It represents an emergency situation which necessitates
      a rapid decision and in particular an exact diagnosis and root cause analysis in
      order to initiate the correct therapeutic measures in an interdisciplinary
      cooperation. In addition to established guidelines, the benefits of standardized
      therapy algorithms have been demonstrated. A therapy algorithm for the obstetric
      emergency of postpartum hemorrhage in the German language is not yet available.
      The establishment of an international (Germany, Austria and Switzerland D-A-CH)
      "treatment algorithm for postpartum hemorrhage" was an interdisciplinary project
      based on the guidelines of the corresponding specialist societies (anesthesia and
      intensive care medicine and obstetrics) in the three countries as well as
      comparable international algorithms for therapy of PPH.The obstetrics and
      anesthesiology personnel must possess sufficient expertise for emergency
      situations despite lower case numbers. The rarity of occurrence for individual
      patients and the life-threatening situation necessitate a structured approach
      according to predetermined treatment algorithms. This can then be carried out
      according to the established algorithm. Furthermore, this algorithm presents the
      opportunity to train for emergency situations in an interdisciplinary team. 

PMID- 24584888
TI  - The incorporation of predictive genomic testing into genetic counseling programs.
AB  - This study explored whether genetic counseling programs are incorporating
      instruction about the applications and techniques of predictive genomic testing
      (PGT) based on student recollection, and whether this is perceived as adequate by
      those students. For the purpose of this study, PGT was defined as the use of
      genome-based testing to assess a person's risk, or susceptibility, of developing
      a disorder with either a known or suspected genetic component. Surveys from 114
      graduates were analyzed. The majority of respondents indicated that PGT was
      covered in their curriculum including methodology, information generated,
      benefits, risks, limitations, and impact on the field of genetic counseling. A
      statistically significant increase in incorporating information about PGT as a
      whole from 2008 to 2011 was also reported. The majority of respondents reported
      that coverage of PGT prepared them for the American Board of Genetic Counseling
      (ABGC) board exam (80.6 %), to interpret PGT test results (60.2 %) and to
      identify clinical situations warranting testing (53.1 %). Although the majority
      of respondents indicated learning about a wide variety of aspects surrounding
      PGT, many recent graduates indicated their training was less likely to cover
      aspects essential for the clinical application of PGT. Therefore, genetic
      counseling programs should place a greater emphasis on these skills, and the
      development of continuing education opportunities aimed at increasing genetic
      counselors abilities to interpret and discuss PGT tests and identify clinical
      situations warranting such testing may be helpful.

PMID- 24584889
TI  - Inclusion complexes of ionic liquids and cyclodextrins: are they formed in the
      gas phase?
AB  - The interaction of imidazolium-based ionic liquids with alpha- and beta
      cyclodextrins was investigated by electrospray ionization mass spectrometry with
      variable collision induced dissociation energy and quantum chemical gas-phase
      calculations. The center-of-mass energy at which 50% of a precursor ion
      decomposes (Ecm,1/2) was determined for the isolated [cyclodextrin + cation](+)
      or [cyclodextrin + anion](-) adduct ions of imidazolium-based ionic liquids with
      different alkyl chain lengths combined with a large set of anions, such as
      chloride, bromide, bis(trifluoromethylsulfonyl)imide, tetrafluoroborate,
      hexafluorophosphate, trifluoromethanesulfonate, methanesulfonate, dicyanamide,
      and hydrogensulfate. Moreover, both symmetric and asymmetric imidazolium cationic
      cores were evaluated. The relative interaction energies in the adduct ions were
      interpreted in terms of the influence of cation/anion structures and their
      inherent properties, such as hydrophobicity and hydrogen bond accepting ability,
      in the complexation process with the cyclodextrins. The trends observed in the
      mass spectral data together with quantum-chemical calculations suggest that in
      the gas phase, cations and anions will preferentially interact with the lower or
      upper rim of the cyclodextrin, respectively, as opposed to what has been reported
      in condensed phase where the formation of an inclusion complex between ionic
      liquid and cyclodextrin is assumed.

PMID- 24584898
TI  - Substituent effects and local molecular shape correlations.
AB  - Using a detailed electron density shape analysis methodology, a new method is
      proposed for studying the main components of substituent effects in a series of
      disubstituted benzenes, in correlation with their activating and deactivating
      characteristics as observed by the induced shape changes of a local electron
      density cloud. The numerical measures obtained for the extent of shape changes
      can be correlated with known and with some unexpected effects of various
      substituents. The insight obtained from the shape analysis provides a
      theoretical, electron density based justification for some well-known trends, but
      it also provides new explanations for some of the unexpected features of these
      substituent effects. 

PMID- 24584899
TI  - Correlation between vividness of visual imagery and echolocation ability in
      sighted, echo-naive people.
AB  - The ability of humans to echolocate has been recognized since the 1940s. Little
      is known about what determines individual differences in echolocation ability,
      however. Although hearing ability has been suggested as an important factor in
      blind people and sighted-trained echolocators, there is evidence to suggest that
      this may not be the case for sighted novices. Therefore, non-auditory aspects of
      human cognition might be relevant. Previous brain imaging studies have shown
      activation of the early 'visual', i.e. calcarine, cortex during echolocation in
      blind echolocation experts, and also during visual imagery in blind and sighted
      people. Therefore, here we investigated the relationship between echolocation
      ability and vividness of visual imagery (VVI). Twenty-four sighted echolocation
      novices completed Marks' (Br J Psychol 1:17-24, 1973) VVI questionnaire and they
      also performed an echolocation size-discrimination task. Furthermore, they
      participated in a battery of auditory tests that determined their ability to
      detect fluctuations in sound frequency and intensity, as well as hearing
      differences between the right and left ear. A correlational analysis revealed a
      significant relationship between participants' VVI and echolocation ability, i.e.
      participants with stronger VVI also had higher echolocation ability, even when
      differences in auditory abilities were taken into account. In terms of underlying
      mechanisms, we suggest that either the use of visual imagery is a strategy for
      echolocation, or that visual imagery and echolocation both depend on the ability
      to recruit calcarine cortex for cognitive tasks that do not rely on retinal
      input. 

PMID- 24584900
TI  - Phosphene-guided transcranial magnetic stimulation of occipital but not parietal
      cortex suppresses stimulus visibility.
AB  - Transcranial magnetic stimulation (TMS) applied over the occipital lobe
      approximately 100 ms after the onset of a stimulus decreases its visibility if it
      appears in the location of the phosphene. Because phosphenes can also be elicited
      by stimulation of the parietal regions, we asked if the same procedure that is
      used to reduce visibility of stimuli with occipital TMS will lead to decreased
      stimulus visibility when TMS is applied to parietal regions. TMS was randomly
      applied at 0-130 ms after the onset of the stimulus in steps of 10 ms in
      occipital and parietal regions. Participants responded to the orientation of the
      line stimulus and rated its visibility. We replicate previous reports of
      phosphenes from both occipital and parietal TMS. As previously reported, we also
      observed visual suppression around the classical 100 ms window both in the
      objective line orientation and subjective visibility responses with occipital
      TMS. Parietal stimulation, on the other hand, did not consistently reduce
      stimulus visibility in any time window.

PMID- 24584901
TI  - Inhibitory effects of resveratrol on foam cell formation are mediated through
      monocyte chemotactic protein-1 and lipid metabolism-related proteins.
AB  - Resveratrol has been shown to exert anti-atherosclerotic effects. 5' AMP
      activated protein kinase (AMPK) and monocyte chemotactic protein-1 (MCP-1) play
      key roles in foam cell formation, which is considered as the initiation of
      atherosclerosis. Thus, in this study, we investigated whether resveratrol
      inhibits foam cell formation by regulating lipid accumulation and inflammation.
      For this purpose, THP-1 cells were treated with 100 nM phorbol 12-myristate 13
      acetate (PMA) to induce their differentiation into macrophages. The macrophages
      were then pre-treated with 2.5 uM resveratrol and subsequently with serum-free
      (SF) medium alone or SF medium containing lipopolysaccharide (LPS; 100 ng/ml) and
      oxidized low-density lipoprotein (ox-LDL; 50 ug/ml) for 24 h to detect foam cell
      formation. To detect the expression of lipid accumulation-related proteins, the
      macrophages were treated with resveratrol. For the detection MCP-1 expression,
      the macrophages were treated with LPS and resveratrol, or with resveratrol alone.
      We incubated the THP-1-derived macrophages in resveratrol (2.5 uM) for 6 h in the
      presence or absence of 30 uM compound C for 4 h to detect the influence of
      compound C on the effects of resveratrol. The foam cells were examined using Red
      O staining. Gene expression levels were determined by qRT-PCR, western blot
      analysis and ELISA; lipid analysis was carried out by high-performance liquid
      chromatography (HPLC). The results revealed that resveratrol effectively
      suppressed foam cell formation induced by LPS. Resveratrol also suppressed lipid
      accumulation and downregulated the mRNA expression of peroxisome proliferator
      activated receptor (PPAR)gamma and PPARalpha, but had no effect on the expression
      of PPARbeta/delta. Resveratrol also upregulated the expression of AMPK and Silent
      information regulator T1 (SIRT1). However, the effects of resveratrol on SIRT1,
      PPARgamma and PPARalpha expression and lipid accumulation were reversed when the
      cells were pre-treated with compound C. Resveratrol downregulated the mRNA
      expression of MCP-1 in a dose-dependent manner and LPS upregulate its expression
      in a time-dependent manner. MCP-1 expression induced by LPS was inhibited by
      resveratrol at both the transcriptional and translational level. These data
      suggest that resveratrol inhibits foam cell formation by regulating the
      expression of MCP-1 and activating the AMPK-SIRT1-PPAR signaling pathway; thus,
      resveratrol may be a novel therapeutic agent for atherosclerosis.

PMID- 24584902
TI  - Acute extracranial occlusion of the internal carotid artery: emergent surgery
      remains a viable option.
AB  - BACKGROUND: Acute symptomatic occlusion of extracranial internal carotid artery
      (eICA) can lead to a critical and potentially devastating stroke associated with
      high morbidity and mortality. Optimal treatment remains unclear. We analyzed our
      institutional experience with emergent surgical recanalization of acutely
      occluded eICA. METHODS: Retrospective analysis of hospital records, surgical
      reports, imaging studies and outpatient records. Final outcome was assessed
      according to modified Rankin Scale (mRS). RESULTS: Between January 2010 and
      September 2013, 22 patients underwent emergent surgical recanalization. There
      were 17 men and five women, mean age 65.4 years (range 37-85). Mean admission
      National Institute of Health Stroke Scale (NIHSS) was 12 (range 6-21). All
      patients had evidence of salvageable penumbra on perfusion computed tomography.
      Tandem intracranial lesion was present in nine patients. Surgical recanalization
      was successful in 16 patients (72.7 %). Twenty-four hours after surgery, 17
      patients (77.2 %) improved by a minimum of 1 point on NIHSS, 14 patients (63.6 %)
      improved by three and more points; two patients deteriorated by two and five
      points, the latter treated initially with systemic thrombolysis due to
      intracranial hemorrhage. No other intracranial hematoma was observed. During 30
      days following surgery, two patients died (9 % mortality rate) due to severity of
      initial stroke. On discharge, four patients were classified as mRS 0, five
      patients as mRS 1, five patients as mRS 2 and six patients as mRS 4. Favorable
      recovery (mRS 0-2) was achieved in 14 patients (63.6 %). No change in mRS was
      observed at three months. CONCLUSIONS: Our results suggest that emergent surgical
      desobliteration of occluded eICA can lead to favorable recovery in a majority of
      patients. Patient selection based on penumbra imaging is crucial. Given the
      popularity and simplicity of carotid endarterectomy, the procedure should by no
      means be abandoned in the treatment of acute eICA occlusion.

PMID- 24584903
TI  - On destabilization of the Fenna-Matthews-Olson complex of Chlorobaculum tepidum.
AB  - The Fenna-Matthews-Olson (FMO) complex from the green sulfur bacterium
      Chlorobaculum tepidum was studied with respect to its stability. We provide a
      critical assessment of published and recently measured optical spectra. FMO
      complexes were found to destabilize over time producing spectral shifts, with
      destabilized samples having significantly higher hole-burning efficiencies;
      indicating a remodeled protein energy landscape. Observed correlated peak shifts
      near 825 and 815 nm suggest possible correlated (protein) fluctuations. It is
      proposed that the value of 35 cm(-1) widely used for reorganization energy (E
      lambda ), which has important implications for the contributions to the coherence
      rate (Kreisbeck and Kramer 3:2828-2833, 2012), in various modeling studies of two
      dimensional electronic spectra is overestimated. We demonstrate that the value of
      E lambda is most likely about 15-22 cm(-1) and suggest that spectra reported in
      the literature (often measured on different FMO samples) exhibit varied peak
      positions due to different purification/isolation procedures or destabilization
      effects. 

PMID- 24584904
TI  - A novel, simple and efficacious technique for tattoo removal resulting in less
      pain using the Q-switched Nd:YAG laser.
AB  - A new yet simple technique has been tested on patients seeking tattoo removal by
      Q-switched Nd:YAG laser based on an observational study. The technique involves
      application of a glass microscope slide on the treatment area with a firm
      pressure to compress the skin which results in evacuating the blood from the
      capillary plexus. Results from a survey of 31 patients revealed that most felt
      less pain and reported less epidermal damage post-treatment. This new technique
      is easy to apply and inexpensive, using standard, conventional Q-switched lasers.

PMID- 24584905
TI  - Disparities in repeat visits to emergency departments among transition-age youths
      with mental health needs.
AB  - OBJECTIVE: The purpose of this study was to examine racial-ethnic and gender
      differences in return visits to emergency services among transition-age youths
      (aged 17 to 24 years) with mental health needs. METHODS: Data were from the
      California Emergency Department and Ambulatory Surgery Data. Logistic regression
      was used to examine the odds of returning to an emergency department among youths
      who had a psychiatric diagnosis (N533,588). RESULTS: About 41% of the sample
      returned to the emergency department within a year. Compared with white males,
      the odds of returning were lower for Hispanic males (odds ratio [OR]5.89) and
      Asian males (OR5.59) and higher for white females (OR51.21), African- American
      females (OR51.49), Hispanic females (OR51.24), and Native American females
      (OR52.09). CONCLUSIONS: Repeat visits to emergency departments among transition
      age youths with psychiatric diagnoses may indicate limited access to or lack of
      high-quality care. The disparities indicate a need for culturally sensitive and
      gender-specific services for this vulnerable population.

PMID- 24584906
TI  - Right gastroepiploic artery arising from the dorsal pancreatic artery: a very
      rare anatomic variation underlying interesting embryologic implications.
AB  - The exceptional case of the right gastroepiploic artery (RGE) arising from the
      dorsal pancreatic (DP) artery in an individual affected by hepatocellular
      carcinoma is presented. This anatomic variant was demonstrated with a selective
      angiography of the common hepatic artery that showed a distinct DP artery
      branching from the injected artery. The DP artery gave off regular pancreatic
      branches and continued as a long and winding vessel that was identified as the
      RGE by its general course, the anterior epiploic branches arising from it, and
      the injection of the distal splenic artery, possibly via the anastomosis with the
      left gastroepiploic artery. The anatomy of the RGE has few variations, mostly
      limited to its origin from the superior mesenteric artery. Arising of the
      gastroepiploic artery from the DP artery has never been previously reported and
      represents an unexpected possible anatomic variant of which general and heart
      surgeons should be aware. In particular, this case is of interest in surgical
      procedures involving resection of the head of the pancreas, gastrectomies or
      coronary artery bypass grafting using the RGE. The embryology underlying the
      development of this anatomic variation is reviewed. 

PMID- 24584907
TI  - Applied anatomy of a minimally invasive muscle-splitting approach to posterior C1
      C2 fusion: an anatomical feasibility study.
AB  - PURPOSE: To describe the applied anatomy of a minimally invasive muscle-splitting
      approach used to reach the posterior aspect of the C1-C2 complex. Atlantoaxial
      fusion using a midline posterior approach and polyaxial screw and rod system is
      widely used. Although minimally invasive variations of this technique have been
      recently reported, the complex applied anatomy of these approaches has not been
      described. The C1-C2 complex represents an unique challenge because of its bony
      and vascular anatomy. In this study, the applied anatomy and feasibility of this
      technique are examined on cadavers. METHODS: The microsurgical anatomy of the
      upper cervical spine is examined on a formalin-fixed and on a fresh cadaver. The
      muscle-splitting approach is performed on 12 fresh cadavers using this technique.
      RESULTS: The minimally invasive muscle-splitting approach is described in detail.
      Relevant anatomy and bony landmarks that aid screw placement in C1 and C2 could
      be well visualized. Using this approach, we were able to reach the lateral mass
      of the atlas and the inferior articular process and pars interarticularis of the
      axis in all of the nine cadavers. We placed mini polyaxial screws in C1 lateral
      mass and C2 pars interarticularis in four cadavers according to the technique
      described by Harms and Melcher. CONCLUSIONS: Using this approach, it was possible
      to reach the posterior aspect of C1 and C2; the relevant anatomy needed to
      perform a C1-C2 fusion could be well visualized.

PMID- 24584908
TI  - A comparative analysis of computational approaches and algorithms for protein
      subcomplex identification.
AB  - High-throughput AP-MS methods have allowed the identification of many protein
      complexes. However, most post-processing methods of this type of data have been
      focused on detection of protein complexes and not its subcomplexes. Here, we
      review the results of some existing methods that may allow subcomplex detection
      and propose alternative methods in order to detect subcomplexes from AP-MS data.
      We assessed and drew comparisons between the use of overlapping clustering
      methods, methods based in the core-attachment model and our own prediction
      strategy (TRIBAL). The hypothesis behind TRIBAL is that subcomplex-building
      information may be concealed in the multiple edges generated by an interaction
      repeated in different contexts in raw data. The CACHET method offered the best
      results when the evaluation of the predicted subcomplexes was carried out using
      both the hypergeometric and geometric scores. TRIBAL offered the best performance
      when using a strict meet-min score. 

PMID- 24584909
TI  - Two middle-age-onset hemochromatosis patients with heterozygous mutations in the
      hemojuvelin gene in a Chinese family.
AB  - Hereditary hemochromatosis is a disorder characterized by enhanced intestinal
      absorption of dietary iron. Here, we report a heterozygous genotype at two
      mutation sites in hemojuvelin (HJV) present in two brothers with middle-age-onset
      hemochromatosis in a Chinese family. To date, only homozygous or compound
      heterozygous states of HJV gene have been reported as associated with iron
      overload. However, the patients here were heterozygous for two mutations in one
      HJV allele in cis: a premature termination mutation (962G>A and 963C>A; C321X)
      and a mutation in the signal peptide (18G>C; Q6H). Previously unrecognized
      environmental or other genetic factors may have interacted with the heterozygous
      genotype in these patients. 

PMID- 24584910
TI  - Gemcitabine-induced large vessel vasculitis demonstrated by PET CT: a rare,
      important side effect.
AB  - Gemcitabine is a nucleoside analogue used widely across haemato-oncology. Side
      effects are generally predictable, and typically consist of cytopenia, nausea,
      and infection. As the present case clearly demonstrates, gemcitabine is in rare
      cases associated with life-threatening large vessel vasculitis, which can involve
      the aorta. It is important to consider gemcitabine-induced vasculitis in non
      specifically unwell patients with raised inflammatory markers and fever of
      unknown origin, with or without signs of vascular compromise. Early recognition,
      cessation of gemcitabine therapy, and high-dose steroids are critical for a good
      outcome. PET CT is valuable to diagnose large vessel vasculitis and monitor
      treatment response. 

PMID- 24584911
TI  - Tumor lysis syndrome in a chronic lymphocytic leukemia patient with pleural
      effusion after oral fludarabine and cyclophosphamide therapy.
AB  - Tumor lysis syndrome (TLS) is a rare complication of the treatment for chronic
      lymphocytic leukemia (CLL). Since the advent of new therapeutic agents with
      higher response rates, however, TLS has been observed with increasing frequency.
      An 84-year-old woman with a nine-year history of untreated CLL presented with
      exacerbating dyspnea due to pleural effusion. CLL cells without Richter
      transformation were observed in the pleural effusion at a high concentration, as
      well as in lymph nodes and bone marrow. After 5 days of oral fludarabine and
      cyclophosphamide (FC) therapy, the patient developed TLS, which necessitated
      rescue with hemodialysis. Although transient exacerbation of pleurisy occurred,
      the effusion cytology ameliorated, and she eventually achieved complete remission
      after additional two courses of FC and rituximab. Sequestration of fludarabine in
      the pleural effusion may be attributable to the development of TLS.

PMID- 24584912
TI  - Transitioning youth with rheumatic conditions: perspectives of pediatric
      rheumatology providers in the United States and Canada.
AB  - OBJECTIVE: To assess North American pediatric rheumatology providers'
      perspectives on practices, barriers, and opportunities concerning the transition
      from pediatric-centered to adult-centered care. METHODS: Childhood Arthritis and
      Rheumatology Research Alliance (CARRA) members completed a 25-item survey
      assessing current transition practices, transition policy awareness, and
      transitional care barriers and needs. Results were compared to the American
      Academy of Pediatrics (AAP) 2008 survey on transitional care. RESULTS: Over half
      (158/288, 55%) of CARRA members completed the survey. Fewer than 10% are very
      familiar with AAP guidelines about transition care for youth with special
      healthcare needs. Eight percent have a formal written transition policy, but 42%
      use an informal approach. Patient request (75%) most frequently initiates
      transfer to adult care. Two major barriers to transition are fragmented adult
      medical care and lack of sufficient time to provide services. Compared with AAP
      survey participants, pediatric rheumatology providers are significantly more
      likely to help youth find an adult specialist (63% vs 45%) and discuss
      confidentiality and consent before age 18 (45% vs 33%), but are less likely to
      help with medical summary creation (16% vs 27%) or find a primary care provider
      (25% vs 47%). Outcomes ranked as "very important" in defining a successful
      transition are survival (76%), seeing an adult rheumatologist within 6 months of
      final pediatric rheumatology visit (66%), and maintaining insurance coverage
      (57%). CONCLUSION: This comprehensive survey of North American pediatric
      rheumatology providers regarding transitional care practices demonstrates
      deficiencies in education, resources, and a formalized process. Respondents
      support development of standardized rheumatology-specific transition practices.

PMID- 24584913
TI  - How to choose core outcome measurement sets for clinical trials: OMERACT 11
      approves filter 2.0.
AB  - OBJECTIVE: The Outcome Measures in Rheumatology (OMERACT) initiative works to
      develop core sets of outcome measures for trials and observational studies in
      rheumatology. At the OMERACT 11 meeting, substantial time was devoted to
      discussing a conceptual framework and a proposal for a more explicit working
      process to develop what we now propose to term core outcome measurement sets,
      collectively termed "OMERACT Filter 2.0." METHODS: Preconference work included a
      literature review, and discussion of preliminary proposals through face-to-face
      discussions and Internet-based surveys with people within and outside
      rheumatology. At the conference, 5 interactive sessions comprising plenary and
      small-group discussions reflected on the proposals from the viewpoint of previous
      and ongoing OMERACT work. These considerations were brought together in a final
      OMERACT presentation seeking consensus agreement for the Filter 2.0 framework.
      RESULTS: After debate, clarification, and agreed alterations, the final proposal
      suggested all core sets should contain at least 1 measurement instrument from 3
      Core Areas: Death, Life Impact, and Pathophysiological Manifestations, and
      preferably 1 from the area Resource Use. The process of core set development for
      a health condition starts by selecting core domains within the areas ("core
      domain set"). This requires literature searches, involvement (especially of
      patients), and at least 1 consensus process. Next, developers select at least 1
      applicable measurement instrument for each core domain. Applicability refers to
      the original OMERACT Filter and means that the instrument must be truthful (face,
      content, and construct validity), discriminative (between situations of interest)
      and feasible (understandable and with acceptable time and monetary costs).
      Depending on the quality of the instruments, participants formulate either a
      preliminary or a final "core outcome measurement set." At final vote, 96% of
      participants agreed "The proposed overall framework for Filter 2.0 is a suitable
      basis on which to elaborate a Filter 2.0 Handbook." CONCLUSION: Within OMERACT,
      Filter 2.0 has made established working processes more explicit and includes a
      broadly endorsed conceptual framework for core outcome measurement set
      development.

PMID- 24584914
TI  - Associations between biomarkers of joint metabolism, hand osteoarthritis, and
      hand pain and function: the Johnston County Osteoarthritis Project.
AB  - OBJECTIVE: To determine the associations between joint metabolism biomarkers and
      hand radiographic osteoarthritis [(rOA), based on Kellgren Lawrence (KL) grade >=
      2], symptoms, and function. METHODS: Cross-sectional data were available for 663
      participants (mean age 63 yrs, 63% white, 49% women). Three definitions of hand
      rOA were considered: (1) a composite measure involving at least 3 hand joints
      distributed bilaterally with 2 of 3 in the same joint group, including >= 1
      distal interphalangeal joint, without metacarpophalangeal (MCP) swelling; (2) rOA
      in at least 1 joint of a group; and (3) number of joints with KL >= 2. We
      assessed hand symptoms and the 15-item Australian Canadian Hand Osteoarthritis
      Index (AUSCAN; Likert format). We measured serum cartilage oligomeric matrix
      protein (sCOMP), hyaluronic acid (sHA), carboxy-terminal propeptide of type II
      collagen, type II collagen degradation product, urinary C-terminal crosslinked
      telopeptide of type II collagen, and urinary N-terminal crosslinked telopeptide.
      Linear regression models were performed to assess associations between each
      biomarker with hand rOA, AUSCAN, and symptoms, adjusting for age, sex, race,
      current smoking/drinking status, body mass index, and hip and knee rOA. RESULTS:
      In adjusted analyses, MCP (p < 0.0001) and carpometacarpal rOA (p = 0.003), and a
      higher number of hand joints with rOA (p = 0.009), were associated with higher
      levels of sHA. Positive associations were seen between AUSCAN and hand symptoms
      and levels of sCOMP (p <= 0.003) and sHA (p <= 0.048). CONCLUSION: Hand symptoms
      and higher AUSCAN scores were independently associated with higher levels of both
      sCOMP and sHA; hand rOA was associated only with sHA levels.

PMID- 24584915
TI  - Joint involvement in patients with early polymyalgia rheumatica using high
      resolution ultrasound and its contribution to the EULAR/ACR 2012 classification
      criteria for polymyalgia rheumatica.
AB  - OBJECTIVE: To assess joint involvement and the contribution of musculoskeletal
      ultrasound (MSUS) to the novel European League Against Rheumatism/American
      College of Rheumatology (EULAR/ACR) 2012 classification criteria in patients with
      polymyalgia rheumatic (PMR). METHODS: MSUS was performed in 54 consecutive
      patients with recent-onset PMR. RESULTS: Biceps tenosynovitis of at least 1
      shoulder has been observed in 70.4% of patients, and 64.8% had a bilateral biceps
      tenosynovitis. Subdeltoid bursitis (27.8% unilateral, 5.6% bilateral),
      glenohumeral synovitis (22.2% unilateral, 9.3% bilateral), and hip involvement
      (22.2% unilateral, 16.7% bilateral) were observed less frequently. The
      sensitivities of the classification criteria were 85.2% for EULAR/ACR without
      MSUS and 81.5% for EULAR/ACR with MSUS. CONCLUSION: The most common MSUS
      pathology was a biceps tenosynovitis. However, US findings had no effect on the
      sensitivity of the novel EULAR/ACR criteria for PMR.

PMID- 24584917
TI  - Can we decide which outcomes should be measured in every clinical trial? A
      scoping review of the existing conceptual frameworks and processes to develop
      core outcome sets.
AB  - OBJECTIVE: The usefulness of randomized control trials to advance clinical care
      depends upon the outcomes reported, but disagreement on the choice of outcome
      measures has resulted in inconsistency and the potential for reporting bias. One
      solution to this problem is the development of a core outcome set: a minimum set
      of outcome measures deemed critical for clinical decision making. Within
      rheumatology the Outcome Measures in Rheumatology (OMERACT) initiative has
      pioneered the development of core outcome sets since 1992. As the number of
      diseases addressed by OMERACT has increased and its experience in formulating
      core sets has grown, clarification and update of the conceptual framework and
      formulation of a more explicit process of area/domain core set development has
      become necessary. As part of the update process of the OMERACT Filter criteria to
      version 2, a literature review was undertaken to compare and contrast the OMERACT
      conceptual framework with others within and outside rheumatology. METHODS: A
      scoping search was undertaken to examine the extent, range, and nature of
      conceptual frameworks for core set outcome selection in health. We searched the
      following resources: Cochrane Library Methods Group Register; Medline; Embase;
      PsycInfo; Environmental Studies and Policy Collection; and ABI/INFORM Global. We
      also conducted a targeted Google search. RESULTS: Five conceptual frameworks were
      identified: the WHO tripartite definition of health; the 5 Ds (discomfort,
      disability, drug toxicity, dollar cost, and death); the International
      Classification of Functioning (ICF); PROMIS (Patient-Reported Outcomes
      Measurement System); and the Outcomes Hierarchy. Of these, only the 5 Ds and ICF
      frameworks have been systematically applied in core set development. Outside the
      area of rheumatology, several core sets were identified; these had been developed
      through a limited range of consensus-based methods with varying degrees of
      methodological rigor. None applied a framework to ensure content validity of the
      end product. CONCLUSION: This scoping review reinforced the need for clear
      methods and standards for core set development. Based on these findings, OMERACT
      will make its own conceptual framework and working process more explicit.
      Proposals for how to achieve this were discussed at the OMERACT 11 conference.

PMID- 24584916
TI  - Updating the OMERACT filter: implications for imaging and soluble biomarkers.
AB  - OBJECTIVE: The Outcome Measures in Rheumatology (OMERACT) Filter provides a
      framework for the validation of outcome measures for use in rheumatology clinical
      research. However, imaging and biochemical measures may face additional
      validation challenges because of their technical nature. The Imaging and Soluble
      Biomarker Session at OMERACT 11 aimed to provide a guide for the iterative
      development of an imaging or biochemical measurement instrument so it can be used
      in therapeutic assessment. METHODS: A hierarchical structure was proposed,
      reflecting 3 dimensions needed for validating an imaging or biochemical
      measurement instrument: outcome domain(s), study setting, and performance of the
      instrument. Movement along the axes in any dimension reflects increasing
      validation. For a given test instrument, the 3-axis structure assesses the extent
      to which the instrument is a validated measure for the chosen domain, whether it
      assesses a patient-centered or disease-centered variable, and whether its
      technical performance is adequate in the context of its application. Some
      currently used imaging and soluble biomarkers for rheumatoid arthritis,
      spondyloarthritis, and knee osteoarthritis were then evaluated using the original
      OMERACT Filter and the newly proposed structure. Breakout groups critically
      reviewed the extent to which the candidate biomarkers complied with the proposed
      stepwise approach, as a way of examining the utility of the proposed 3
      dimensional structure. RESULTS: Although there was a broad acceptance of the
      value of the proposed structure in general, some areas for improvement were
      suggested including clarification of criteria for achieving a certain level of
      validation and how to deal with extension of the structure to areas beyond
      clinical trials. CONCLUSION: General support was obtained for a proposed tri-axis
      structure to assess validation of imaging and soluble biomarkers; nevertheless,
      additional work is required to better evaluate its place within the OMERACT
      Filter 2.0.

PMID- 24584919
TI  - Updating the OMERACT filter: implications for patient-reported outcomes.
AB  - OBJECTIVE: At a previous Outcome Measures in Rheumatology (OMERACT) meeting,
      participants reflected on the underlying methods of patient-reported outcome
      (PRO) instrument development. The participants requested proposals for more
      explicit instrument development protocols that would contribute to an enhanced
      version of the "Truth" statement in the OMERACT Filter, a widely used guide for
      outcome validation. In the present OMERACT session, we explored to what extent
      these new Filter 2.0 proposals were practicable, feasible, and already being
      applied. METHODS: Following overview presentations, discussion groups critically
      reviewed the extent to which case studies of current OMERACT Working Groups
      complied with or negated the proposed PRO development framework, whether these
      observations had a more general application, and what issues remained to be
      resolved. RESULTS: Several aspects of PRO development were recognized as
      particularly important, and the need to directly involve patients at every stage
      of an iterative PRO development program was endorsed. This included recognition
      that patients contribute as partners in the research and not merely as subjects.
      Correct communication of concepts with the words used in questionnaires was
      central to their performance as measuring instruments, and ensuring this
      understanding crossed cultural and linguistic boundaries was important in
      international studies or comparisons. CONCLUSION: Participants recognized,
      endorsed, and were generally already putting into practice the principles of PRO
      development presented in the plenary session. Further work is needed on some
      existing instruments and on establishing widespread good practice for working in
      close collaboration with patients.

PMID- 24584918
TI  - Vaccine responses in patients with rheumatoid arthritis treated with certolizumab
      pegol: results from a single-blind randomized phase IV trial.
AB  - OBJECTIVE: To evaluate the humoral immune response to pneumococcal and influenza
      vaccination in adults with rheumatoid arthritis (RA) receiving certolizumab pegol
      (CZP). METHODS: In this 6-week, single-blind, placebo-controlled trial with
      optional 6-month open-label extension (NCT00993668), patients were stratified by
      concomitant methotrexate (MTX) use and randomized to receive CZP 400 mg (loading
      dose; according to CZP label) or placebo at weeks 0, 2, and 4. Pneumococcal
      (polysaccharide 23) and influenza vaccines were administered at Week 2.
      Satisfactory humoral immune response, defined as >=2-fold titer increase in >=3
      of 6 pneumococcal antigens and >=4-fold titer increase in >=2 of 3 influenza
      antigens, were assessed independently 4 weeks after vaccination. RESULTS:
      Following pneumococcal vaccination, 62.5% of placebo patients and 54.5% of CZP
      patients without effective titers at baseline achieved a humoral response
      (difference in proportions was -8.0 percentage points; 95% CI -22.5 to 6.6%).
      Following influenza vaccination, 61.4% of placebo and 53.5% of CZP patients
      without effective titers at baseline achieved a humoral response (difference in
      proportions: -8.0 percentage points; 95% CI -22.9 to 7.0%). In all patients,
      including those with effective titers at baseline, 58.2% of placebo and 53.3% of
      CZP patients developed satisfactory pneumococcal titers, and 54.1% of placebo and
      50.5% of CZP patients developed satisfactory influenza antibody titers. Vaccine
      responses to pneumococcal and influenza antigens were reduced similarly in both
      treatment groups with concomitant MTX use. CONCLUSION: Humoral immune responses
      to pneumococcal and influenza vaccination are not impaired when given during the
      loading phase of CZP treatment in patients with RA. (ClinicalTrials.gov
      NCT00993668).

PMID- 24584920
TI  - Impaired left ventricular apical rotation is associated with disease activity of
      psoriatic arthritis.
AB  - OBJECTIVE: Although early cardiovascular (CV) involvement has been found in
      patients with psoriatic arthritis (PsA), few studies have related this to PsA
      disease activity. The aim of our study was to evaluate left ventricular (LV)
      mechanics using novel, more sensitive techniques based on assessment of LV
      rotation for the detection of impaired LV function in patients with PsA
      correlated with disease-related risk factors. METHODS: Seventy-six patients with
      PsA and 24 healthy control subjects were enrolled, including 33 patients without
      any CV risk factors. All participants underwent conventional echocardiography and
      2-dimensional speckle tracking imaging. Global longitudinal, apical
      circumferential, and radial strain, and apical rotation and maximal untwisting
      rate during early diastole were measured. RESULTS: Although patients with PsA had
      normal LV ejection fraction, the myocardial deformation in multidimensional
      planes was impaired. Based on the cutoff point derived from the apical rotation
      of control subjects, 81% of the patients had subclinical systolic and/or
      diastolic dysfunction. Similar prevalence was found in patients without CV risk
      factors. Spearman correlation demonstrated a relationship between Disease
      Activity Score in 28 joints (r=0.299, p=0.011), erythrocyte sedimentation rate
      (r=0.309, p=0.008), and impaired apical rotation, even after adjusting for age
      and hypertension. No correlation was found between longitudinal, radial, and
      circumferential strain and disease activity. CONCLUSION: Subclinical impaired
      myocardial deformation was common in patients with PsA even without CV risk
      factors. Apical rotation was associated with the status of PsA disease activity.
      These new speckle tracking echocardiography techniques can detect subclinical
      myocardial involvement in PsA.

PMID- 24584921
TI  - Treatment of asymptomatic hyperuricemia and prevention of vascular disease: a
      decision analytic approach.
AB  - OBJECTIVE: Elevated serum urate may be associated with an increase in
      cardiovascular (CV) disease. Treating asymptomatic hyperuricemia with urate
      lowering drugs such as allopurinol may reduce CV events. We designed a model to
      simulate the effect of allopurinol treatment on reducing frequency of CV events
      in individuals with elevated serum urate. METHODS: A Markov state-transition
      model was constructed to assess occurrence of vascular events (VE) for 2
      treatment strategies: treat all asymptomatic individuals with allopurinol (Treat
      All) and treat only if symptomatic (Treat Symptomatic). The model simulated a
      hypothetical cohort of 50-year-old men with different serum urate concentrations
      (6-6.9 and 7-7.9 mg/dl) followed over 20 years. Age and sex subgroups were
      analyzed. Model inputs were derived from current literature. The main outcome
      measures were mean number of VE and mean number of deaths from VE. RESULTS: For
      50-year-old men with serum urate 6.0-6.9 mg/dl, individuals in the Treat All
      strategy have a 30% reduction in the mean number of VE compared to those in the
      Treat Symptomatic strategy (mean VE: 0.078 vs 0.11), and a 39% reduction in mean
      number of deaths from VE. At higher serum urate concentrations, treatment is more
      effective in reducing the mean number of VE and mean number of deaths from VE
      (38% event, 54% death). Results for women show similar trends. As the cohort
      ages, treatment has less effect on reducing VE. The number needed to treat to
      prevent 1 event is 20 (men, 7.0-7.9 mg/dl). CONCLUSION: The model predicts that
      treating asymptomatic hyperuricemia with allopurinol is most effective in
      preventing VE at a serum urate above 7.0 mg/dl in men and 5.0 mg/dl in women.

PMID- 24584922
TI  - Toward a generalized framework of core measurement areas in clinical trials: a
      position paper for OMERACT 11.
AB  - OBJECTIVE: The Outcome Measures in Rheumatology (OMERACT) international consensus
      initiative has successfully developed core sets of outcome measures for trials of
      many rheumatologic conditions, but its expanding scope called for clarification
      and updating of its underlying conceptual framework and working process. To
      develop a core set of what we propose to call outcome measurement instruments,
      consensus must be reached both on what to measure and how to measure. This
      article deals with the first part: a framework necessary to ensure
      comprehensiveness of the domains chosen for measurement. We formulated a
      conceptual framework of core measurement areas in clinical trials, for discussion
      at the OMERACT 11 conference. METHODS: We formulated a framework and definitions
      of key concepts adapted from the literature, and followed an iterative consensus
      process (small group processes and an Internet-based survey) of those involved
      including patients, health professionals, and methodologists within and outside
      rheumatology. RESULTS: The draft framework comprises 4 core "areas": death, life
      impact (all aspects of how a patient feels or functions), resource use (monetary
      and other costs of the health condition and interventions), and pathophysiologic
      manifestations (disease-specific clinical and psychological signs, biomarkers,
      and potential surrogate outcome measures necessary to assess specific effects).
      The survey responses (262 of 2293, response rate 11%) indicated broad agreement
      with the draft framework and the proposed definitions of key concepts, including
      understandability and feasibility. A total of 283 comments were processed.
      CONCLUSION: In an iterative process, we have developed a generic framework for
      outcome measurement and working definitions of key concepts ready for discussion
      at the OMERACT 11 conference.

PMID- 24584923
TI  - Frailty index to measure health status in people with systemic sclerosis.
AB  - OBJECTIVE: To develop and validate, as a measure of overall health status, a
      Frailty Index (FI) for patients (n=1372) in the Canadian Scleroderma Research
      Group (CSRG) Registry. METHODS: Forty-four items were selected from the CSRG
      database as health deficits and recoded using FI criteria. To test construct
      validity, we compared measurement properties of the CSRG-FI to other FI, and
      related it to measures of damage, age, and time since diagnosis. To test
      criterion validity, we compared the baseline FI to that at last recorded visit
      and to mortality. RESULTS: The mean CSRG-FI was 0.33 with a sub-maximal limit of
      0.67. In patients with diffuse disease, the mean was 0.38(SD 0.14); in patients
      with limited disease, the mean was 0.31(SD 0.13). The CSRG-FI was weakly (but
      significantly) correlated with the Rodnan Skin Score (r=0.28 in people with
      diffuse disease; 0.18 with limited) and moderately with the Physician Assessment
      of Damage (r=0.51 for both limited and diffuse). The risk of death increased with
      higher FI scores and with higher physician ratings of damage. The area under the
      receiver operating characteristic curve for the baseline FI in relation to death
      was 0.75, higher than for other measures (range: 0.57-0.67). CONCLUSION: The FI
      quantifies overall health status in people with scleroderma and predicts
      mortality. Whether the FI might help with decisions about who might best be
      served by more aggressive treatment, such as bone marrow transplantation, needs
      to be evaluated.

PMID- 24584924
TI  - Abatacept reduces levels of switched memory B cells, autoantibodies, and
      immunoglobulins in patients with rheumatoid arthritis.
AB  - OBJECTIVE: Abatacept (ABA) is a chimeric molecule, able to block the CD28
      mediated costimulatory pathway. To evaluate the hypothesis that, through this
      mechanism of action, ABA may down-modulate the immune responses of B lymphocytes
      in rheumatoid arthritis (RA), we investigated the serum levels of immunoglobulins
      (Ig), free light chains (FLC), anticitrullinated protein antibodies (ACPA), and
      rheumatoid factor (RF), as well as the number of B lymphocytes differentiated
      into post-switch memory cells in patients treated with ABA. METHODS: The serum
      levels of Ig, FLC, different ACPA, RF isotypes, and the B cell phenotype were
      longitudinally evaluated in 30 patients with RA treated with ABA. RESULTS: At
      baseline, the proportion of total and post-switch memory B cells was lower in RA
      than in healthy individuals. After 6 months of ABA treatment we observed
      significant reductions of serum levels of IgG, IgA, and IgM, as well as FLC, with
      a normalization in many patients who had initially abnormal values. A significant
      reduction of the titers of IgG- and IgA-ACPA, as well as of IgM-, IgA-, and IgG
      RF was also observed. A decrease of autoantibodies below the upper limits of
      normal values was found in 2 of 26 patients (8%) initially seropositive for IgG
      ACPA, 1 of 14 (7%) for IgA-ACPA, 5 of 22 (23%) for IgM-RF, 7 of 22 (30%) for IgA
      RF, and 5 of 16 (31%) for IgG-RF. After treatment, the proportion of circulating
      post-switch memory B cells was also further significantly decreased. CONCLUSION:
      ABA treatment in patients with RA can reduce signs of polyclonal B cell
      activation, inducing a trend toward normalization of serum levels of different
      classes of Ig and of FLC, decreasing titers of ACPA and RF, and percentages of
      post-switch memory B cells.

PMID- 24584925
TI  - Factors associated with major cardiovascular events in patients with systemic
      necrotizing vasculitides: results of a longterm followup study.
AB  - OBJECTIVE: Systemic necrotizing vasculitides (SNV) are associated with more
      frequent subclinical atherosclerosis, suggesting that SNV might be associated
      with a higher risk of major cardiovascular events (MCVE). We aimed to identify
      factors predictive of MCVE in patients with SNV. METHODS: Patients in remission
      from SNV were assessed for CV risk factors and subclinical atherosclerosis. MCVE
      was defined as myocardial infarction, stroke, arterial revascularization,
      hospitalization for unstable angina, and/or death from CV causes. MCVE-free
      survival curves were compared using the log-rank test. RESULTS: Forty-two
      patients were followed for 7.1+/-2.6 years. Eight patients (18.9%) had MCVE. The
      respective 5- and 10-year MCVE rates were 9.5% and 26.8%. National Cholesterol
      Education Program/Adult Treatment Panel III (NCEP/ATP III)-defined high-risk
      status [hazard ratio (HR) 5.02 (95% CI: 1.17-27.4), p=0.03], BMI>30 kg/m2 [HR
      4.84 (95% CI: 1.46-116), p=0.02], and plaque detection in the abdominal aorta
      (p=0.01) were significantly associated with MCVE. SNV characteristics,
      corticosteroid maintenance therapy, and C-reactive protein>5 mg/l were not
      associated with MCVE. Plaque in the aorta was significantly associated with high
      risk status (p<0.001), while BMI and high-risk status were independent variables.
      Thus, a BMI>30 kg/m2 and/or a high-risk status were strongly associated with MCVE
      (p=0.004). Carotid intima-media thickness (IMT) identified patients with early
      MCVE and was correlated with the time to MCVE (r2=0.68, p=0.01). CONCLUSION:
      These results suggest that factors associated with a higher MCVE risk in patients
      with SNV are NCEP/ATP III-defined high-risk status and BMI>30 kg/m2. Carotid IMT
      could help identify patients with SNV at risk of early MCVE.

PMID- 24584926
TI  - Subcutaneous abatacept for the treatment of rheumatoid arthritis: longterm data
      from the ACQUIRE trial.
AB  - OBJECTIVE: Assess longterm tolerability, safety, and efficacy of subcutaneous
      (SC) abatacept (ABA) in methotrexate-refractory patients with rheumatoid
      arthritis (RA). METHODS: The phase III, multinational Abatacept Comparison of
      Sub[QU]cutaneous Versus Intravenous in Inadequate Responders to MethotrexatE
      (ACQUIRE) trial comprised a 6-month, randomized, double-blind (DB) period, in
      which patients received intravenous (IV) or SC ABA, plus MTX, followed by an open
      label, longterm extension (LTE), in which patients received SC ABA, 125 mg/week.
      Safety and efficacy from the LTE (~3.5 yrs of exposure) are reported. RESULTS:
      Patients who completed the DB period (1372/1385, 99.1%) entered the LTE; 1134
      patients (82.7%) kept taking the treatment at time of reporting. Mean (SD) was
      31.9 months (6.8); median (range) exposure was 33.0 (8-44) months. Patients
      entering the LTE had longstanding, moderate-to-severe disease [mean 7.6 (7.9) yrs
      and DAS28 (C-reactive protein) 6.2 (0.9)]. Incidence rates (events/100 patient
      yrs) were reported for serious adverse events (8.76, 95% CI 7.71, 9.95),
      infections (44.80, 95% CI 41.76, 48.01), serious infections (1.72, 95% CI 1.30,
      2.27), malignancies (1.19, 95% CI 0.86, 1.66), and autoimmune events (1.31, 95%
      CI 0.95, 1.79). Twenty-seven patients (2%) experienced injection-site reactions;
      all except 1 were mild. American College of Rheumatology 20, 50, and 70 responses
      achieved during the DB period were maintained through the LTE, and on Day 981
      were 80.2% (95% CI 77.2, 83.2), 63.5% (95% CI 58.2, 68.9), and 39.5% (95% CI
      34.0, 44.9) for patients who kept taking SC ABA, and 80.0% (95% CI 77.0, 83.0),
      63.2% (95% CI 57.8, 68.7), and 39.2% (95% CI 33.7, 44.7) for those who switched
      from IV to SC ABA. CONCLUSION: These findings support SC ABA as a well-tolerated
      and efficacious longterm treatment for patients with RA and inadequate response
      to MTX (ClinicalTrials.gov identifier NCT00559585).

PMID- 24584927
TI  - Establishing a core domain set to measure rheumatoid arthritis flares: report of
      the OMERACT 11 RA flare Workshop.
AB  - OBJECTIVE: The OMERACT Rheumatoid Arthritis (RA) Flare Group (FG) is developing a
      data-driven, patient-inclusive, consensus-based RA flare definition for use in
      clinical trials, longterm observational studies, and clinical practice. At
      OMERACT 11, we sought endorsement of a proposed core domain set to measure RA
      flare. METHODS: Patient and healthcare professional (HCP) qualitative studies,
      focus groups, and literature review, followed by patient and HCP Delphi exercises
      including combined Delphi consensus at Outcome Measures in Rheumatology 10
      (OMERACT 10), identified potential domains to measure flare. At OMERACT 11,
      breakout groups discussed key domains and instruments to measure them, and
      proposed a research agenda. Patients were active research partners in all focus
      groups and domain identification activities. Processes for domain selection and
      patient partner involvement were case studies for OMERACT Filter 2.0 methodology.
      RESULTS: A pre-meeting combined Delphi exercise for defining flare identified 9
      domains as important (>70% consensus from patients or HCP). Four new patient
      reported domains beyond those included in the RA disease activity core set were
      proposed for inclusion (fatigue, participation, stiffness, and self-management).
      The RA FG developed preliminary flare questions (PFQ) to measure domains. In
      combined plenary voting sessions, OMERACT 11 attendees endorsed the proposed RA
      core set to measure flare with >=78% consensus and the addition of 3 additional
      domains to the research agenda for OMERACT 12. CONCLUSION: At OMERACT 11, a core
      domain set to measure RA flare was ratified and endorsed by attendees. Domain
      validation aligning with Filter 2.0 is ongoing in new randomized controlled
      clinical trials and longitudinal observational studies using existing and new
      instruments including a set of PFQ.

PMID- 24584928
TI  - Systemic autoimmune rheumatic disease prevalence in Canada: updated analyses
      across 7 provinces.
AB  - OBJECTIVE: To estimate systemic autoimmune rheumatic disease (SARD) prevalence
      across 7 Canadian provinces using population-based administrative data evaluating
      both regional variations and the effects of age and sex. METHODS: Using
      provincial physician billing and hospitalization data, cases of SARD (systemic
      lupus erythematosus, scleroderma, primary Sjogren syndrome,
      polymyositis/dermatomyositis) were ascertained. Three case definitions
      (rheumatology billing, 2-code physician billing, and hospital diagnosis) were
      combined to derive a SARD prevalence estimate for each province, categorized by
      age, sex, and rural/urban status. A hierarchical Bayesian latent class regression
      model was fit to account for the imperfect sensitivity and specificity of each
      case definition. The model also provided sensitivity estimates of different case
      definition approaches. RESULTS: Prevalence estimates for overall SARD ranged
      between 2 and 5 cases per 1000 residents across provinces. Similar demographic
      trends were evident across provinces, with greater prevalence in women and in
      persons over 45 years old. SARD prevalence in women over 45 was close to 1%.
      Overall sensitivity was poor, but estimates for each of the 3 case definitions
      improved within older populations and were slightly higher for men compared to
      women. CONCLUSION: Our results are consistent with previous estimates and other
      North American findings, and provide results from coast to coast, as well as
      useful information about the degree of regional and demographic variations that
      can be seen within a single country. Our work demonstrates the usefulness of
      using multiple data sources, adjusting for the error in each, and providing
      estimates of the sensitivity of different case definition approaches.

PMID- 24584929
TI  - Coffee consumption and prostate cancer risk: an updated meta-analysis.
AB  - PURPOSE: Many epidemiological studies have been conducted to explore the
      association between coffee consumption and prostate cancer. However, the results
      remain inconsistent. We performed a large meta-analysis of relevant studies to
      derive a more precise estimation of this relationship. METHODS: Systematic
      searches of PubMed and several other databases up to June 2013 were retrieved.
      All epidemiologic studies regarding coffee consumption and prostate cancer risk
      were included, and odds ratios (ORs) with 95 % confidence intervals (CIs) were
      calculated to estimate the strength of the association. RESULTS: Twelve case
      control studies involving 7,909 prostate cancer cases and 9,461 controls and nine
      cohort studies involving 455,123 subjects were included in our analysis. Compared
      with the lowest category, the unstratified highest category of coffee consumption
      showed a significance reduction in prostate cancer risk of a fixed-effects model
      (OR 0.91, CI 0.86-0.97). A borderline significant influence was also found when
      the stratified highest category (US >= 4, Europe >= 5) of coffee consumption was
      compared with the reference category (OR 0.96, CI 0.92-1.00), but no
      relationships were observed for the other two categories. In another analysis
      conducted by coffee consumption and prostate cancer stage and Gleason grade, our
      results showed a significant inverse association in all categories of prostate
      cancer except Gleason <7 grade in a fixed-effects model; the results remained the
      same, except for advanced prostate cancer, in a random-effects model.
      CONCLUSIONS: Our meta-analysis suggests that high (e.g., highest >= 4 or 5
      cups/day) coffee consumption may not only be associated with a reduced risk of
      overall prostate cancer, but also inversely associated with fatal and high-grade
      prostate cancer.

PMID- 24584930
TI  - Mammal-specific H2A variant, H2ABbd, is involved in apoptotic induction via
      activation of NF-kappaB signaling pathway.
AB  - Histone variants play specific roles in maintenance and regulation of chromatin
      structures. H2ABbd, an H2A variant, possesses a highly divergent structure
      compared with canonical H2A and is highly expressed in postmeiotic germ cells,
      but its functions in the regulation of gene expression are largely unknown. In
      the present study, we investigated the cellular phenotype associated with
      enforced H2ABbd expression. Among H2A variants, H2ABbd specifically caused growth
      defect in human cells and induced apoptosis. H2ABbd expression resulted in
      degradation of inhibitor of kappaB-alpha and translocation of NF-kappaB into
      nuclei, indicating the activation of NF-kappaB. Intriguingly, NF-kappaB activity
      was essential for H2ABbd-induced apoptosis. H2ABbd overexpression resulted in DNA
      damage after release from G1/S, progressed through the S phase slowly, and
      induced apoptosis. Furthermore, gene expression microarray analysis revealed that
      expression of H2ABbd activates groups of genes involved in apoptosis and
      postmeiotic germ cell development, suggesting that H2ABbd might influence
      transcription. Taken together, our data suggest that H2ABbd may contribute to
      specific chromatin structures and promote NF-kappaB activation, which could in
      turn induce apoptosis in mammalian cells. 

PMID- 24584931
TI  - Disulfide cross-linking of transport and trimerization domains of a neuronal
      glutamate transporter restricts the role of the substrate to the gating of the
      anion conductance.
AB  - Excitatory amino acid transporters remove synaptically released glutamate and
      maintain its concentrations below neurotoxic levels. EAATs also mediate a
      thermodynamically uncoupled substrate-gated anion conductance that may modulate
      cell excitability. A structure of an archeal homologue, which reflects an early
      intermediate on the proposed substrate translocation path, has been suggested to
      be similar to an anion conducting conformation. To probe this idea by functional
      studies, we have introduced two cysteine residues in the neuronal glutamate
      transporter EAAC1 at positions predicted to be close enough to form a disulfide
      bond only in outward-facing and early intermediate conformations of the
      homologue. Upon treatment of Xenopus laevis oocytes expressing the W441C/K269C
      double mutant with dithiothreitol, radioactive transport was stimulated >2-fold
      but potently inhibited by low micromolar concentrations of the oxidizing reagent
      copper(II)(1,10-phenanthroline)3. The substrate-induced currents by the untreated
      double mutant, reversed at approximately -20 mV, close to the reversal potential
      of chloride, but treatment with dithiothreitol resulted in transport currents
      with the same voltage dependence as the wild type. It appears therefore that in
      the oocyte expression system the introduced cysteine residues in many of the
      mutant transporters are already cross-linked and are only capable of mediating
      the substrate-gated anion conductance. Reduction of the disulfide bond now allows
      these transporters to execute the full transport cycle. Our functional data
      support the idea that the anion conducting conformation of the neuronal glutamate
      transporter is associated with an early step of the transport cycle. 

PMID- 24584932
TI  - The GTPase-deficient Rab27A(Q78L) mutant inhibits melanosome transport in
      melanocytes through trapping of Rab27A effector protein Slac2-a/melanophilin in
      their cytosol: development of a novel melanosome-targetinG tag.
AB  - The small GTPase Rab27A is a crucial regulator of actin-based melanosome
      transport in melanocytes, and functionally defective Rab27A causes human
      Griscelli syndrome type 2, which is characterized by silvery hair. A GTPase
      deficient, constitutively active Rab27A(Q78L) mutant has been shown to act as an
      inhibitor of melanosome transport and to induce perinuclear aggregation of
      melanosomes, but the molecular mechanism by which Rab27A(Q78L) inhibits
      melanosome transport remained to be determined. In this study, we attempted to
      identify the primary cause of the perinuclear melanosome aggregation induced by
      Rab27A(Q78L). The results showed that Rab27A(Q78L) is unable to localize on
      mature melanosomes and that its inhibitory activity on melanosome transport is
      completely dependent on its binding to the Rab27A effector Slac2-a/melanophilin.
      When we forcibly expressed Rab27A(Q78L) on mature melanosomes by using a novel
      melanosome-targeting tag that we developed in this study and named the MST tag,
      the MST-Rab27A(Q78L) fusion protein behaved in the same manner as wild-type
      Rab27A. It localized on mature melanosomes without inducing melanosome
      aggregation and restored normal peripheral melanosome distribution in Rab27A
      deficient cells. These findings indicate that the GTPase activity of Rab27A is
      required for its melanosome localization but is not required for melanosome
      transport. 

PMID- 24584933
TI  - Steroid receptor coactivator-3 regulates glucose metabolism in bladder cancer
      cells through coactivation of hypoxia inducible factor 1alpha.
AB  - Cancer cell proliferation is a metabolically demanding process, requiring high
      glycolysis, which is known as "Warburg effect," to support anabolic growth.
      Steroid receptor coactivator-3 (SRC-3), a steroid receptor coactivator, is
      overexpressed and/or amplified in multiple cancer types, including non-steroid
      targeted cancers, such as urinary bladder cancer (UBC). However, whether SRC-3
      regulates the metabolic reprogramming for cancer cell growth is unknown. Here, we
      reported that overexpression of SRC-3 accelerated UBC cell growth, accompanied by
      the increased expression of genes involved in glycolysis. Knockdown of SRC-3
      reduced the UBC cell glycolytic rate under hypoxia, decreased tumor growth in
      nude mice, with reduction of proliferating cell nuclear antigen and lactate
      dehydrogenase expression levels. We further revealed that SRC-3 could interact
      with hypoxia inducible factor 1alpha (HIF1alpha), which is a key transcription
      factor required for glycolysis, and coactivate its transcriptional activity. SRC
      3 was recruited to the promoters of HIF1alpha-target genes, such as glut1 and
      pgk1. The positive correlation of expression levels between SRC-3 and Glut1
      proteins was demonstrated in human UBC patient samples. Inhibition of glycolysis
      through targeting HK2 or LDHA decelerated SRC-3 overexpression-induced cell
      growth. In summary, overexpression of SRC-3 promoted glycolysis in bladder cancer
      cells through HIF1alpha to facilitate tumorigenesis, which may be an intriguing
      drug target for bladder cancer therapy. 

PMID- 24584934
TI  - Structure and mechanism of soybean ATP sulfurylase and the committed step in
      plant sulfur assimilation.
AB  - Enzymes of the sulfur assimilation pathway are potential targets for improving
      nutrient content and environmental stress responses in plants. The committed step
      in this pathway is catalyzed by ATP sulfurylase, which synthesizes adenosine 5'
      phosphosulfate (APS) from sulfate and ATP. To better understand the molecular
      basis of this energetically unfavorable reaction, the x-ray crystal structure of
      ATP sulfurylase isoform 1 from soybean (Glycine max ATP sulfurylase) in complex
      with APS was determined. This structure revealed several highly conserved
      substrate-binding motifs in the active site and a distinct dimerization interface
      compared with other ATP sulfurylases but was similar to mammalian 3'
      phosphoadenosine 5'-phosphosulfate synthetase. Steady-state kinetic analysis of
      20 G. max ATP sulfurylase point mutants suggests a reaction mechanism in which
      nucleophilic attack by sulfate on the alpha-phosphate of ATP involves transition
      state stabilization by Arg-248, Asn-249, His-255, and Arg-349. The structure and
      kinetic analysis suggest that ATP sulfurylase overcomes the energetic barrier of
      APS synthesis by distorting nucleotide structure and identifies critical residues
      for catalysis. Mutations that alter sulfate assimilation in Arabidopsis were
      mapped to the structure, which provides a molecular basis for understanding their
      effects on the sulfur assimilation pathway. 

PMID- 24584935
TI  - Hyperactivation of the human plasma membrane Ca2+ pump PMCA h4xb by mutation of
      Glu99 to Lys.
AB  - The transport of calcium to the extracellular space carried out by plasma
      membrane Ca(2+) pumps (PMCAs) is essential for maintaining low Ca(2+)
      concentrations in the cytosol of eukaryotic cells. The activity of PMCAs is
      controlled by autoinhibition. Autoinhibition is relieved by the binding of Ca(2+)
      calmodulin to the calmodulin-binding autoinhibitory sequence, which in the human
      PMCA is located in the C-terminal segment and results in a PMCA of high maximal
      velocity of transport and high affinity for Ca(2+). Autoinhibition involves the
      intramolecular interaction between the autoinhibitory domain and a not well
      defined region of the molecule near the catalytic site. Here we show that the
      fusion of GFP to the C terminus of the h4xb PMCA causes partial loss of
      autoinhibition by specifically increasing the Vmax. Mutation of residue Glu(99)
      to Lys in the cytosolic portion of the M1 transmembrane helix at the other end of
      the molecule brought the Vmax of the h4xb PMCA to near that of the calmodulin
      activated enzyme without increasing the apparent affinity for Ca(2+). Altogether,
      the results suggest that the autoinhibitory interaction of the extreme C-terminal
      segment of the h4 PMCA is disturbed by changes of negatively charged residues of
      the N-terminal region. This would be consistent with a recently proposed model of
      an autoinhibited form of the plant ACA8 pump, although some differences are
      noted. 

PMID- 24584936
TI  - Anti-amyloid compounds inhibit alpha-synuclein aggregation induced by protein
      misfolding cyclic amplification (PMCA).
AB  - Filaments made of alpha-synuclein form the characteristic Lewy pathology in
      Parkinson and other diseases. The formation of alpha-synuclein filaments can be
      reproduced in vitro by incubation of recombinant protein, but the filament growth
      is very slow and highly variable and so unsuitable for fast high throughput anti
      aggregation drug screening. To overcome this obstacle we have investigated
      whether the protein misfolding cyclic amplification (PMCA) technique, used for
      fast amplification of prion protein aggregates, could be adapted for growing
      alpha-synuclein aggregates and thus suitable for screening of drugs to affect
      alpha-synuclein aggregation for the treatment of the yet incurable alpha
      synucleinopathies. Circular dichroism, electron microscopy, and native and SDS
      polyacrylamide gels were used to demonstrate alpha-synuclein aggregate formation
      by PMCA, and the strain imprint of the alpha-synuclein fibrils was studied by
      proteinase K digestion. We also demonstrated that alpha-synuclein fibrils are
      able to seed new alpha-synuclein PMCA reactions and to enter and aggregate in
      cells in culture. In particular, we have generated a line of "chronically
      infected" cells, which transmit alpha-synuclein aggregates even after multiple
      passages. To evaluate the sensitivity of the PMCA system as an alpha-synuclein
      anti-aggregating drug screening assay a panel of 10 drugs was tested. Anti
      amyloid compounds proved efficient in inhibiting alpha-synuclein fibril formation
      induced by PMCA. Our results show that alpha-synuclein PMCA is a fast and
      reproducible system that could be used as a high throughput screening method for
      finding new alpha-synuclein anti-aggregating compounds. 

PMID- 24584937
TI  - Sj7170, a unique dual-function peptide with a specific alpha-chymotrypsin
      inhibitory activity and a potent tumor-activating effect from scorpion venom.
AB  - A new peptide precursor, termed Sj7170, was characterized from the venomous gland
      cDNA library of the scorpion Scorpiops jendeki. Sj7170 was deduced to be a 62
      amino acid peptide cross-linked by five disulfide bridges. The recombinant Sj7170
      peptide (rSj7170) with chromatographic purity was produced by a prokaryotic
      expression system. Enzyme inhibition assay in vitro and in vivo showed that
      rSj7170 specifically inhibited the activity of alpha-chymotrypsin at micromole
      concentrations. In addition, Sj7170 not only promoted cell proliferation and
      colony formation by up-regulating the expression of cyclin D1 in vitro but also
      enhanced tumor growth in nude mice. Finally, Sj7170 accelerated cellular
      migration and invasion by increasing the expression of the transcription factor
      Snail and then inducing the epithelial-mesenchymal transition. Moreover, Sj7170
      changed cell morphology and cytoskeleton of U87 cells by the GTPase pathway.
      Taken together, Sj7170 is a unique dual-function peptide, i.e. a specific alpha
      chymotrypsin inhibitor and a potent tumorigenesis/metastasis activator. Our work
      not only opens an avenue of developing new modulators of tumorigenesis/metastasis
      from serine protease inhibitors but also strengthens the functional link between
      protease inhibitors and tumor activators. 

PMID- 24584938
TI  - Computational and experimental studies on beta-sheet breakers targeting Abeta1-40
      fibrils.
AB  - In this work we present and compare the results of extensive molecular dynamics
      simulations of model systems comprising an Abeta1-40 peptide in water in
      interaction with short peptides (beta-sheet breakers) mimicking the 17-21 region
      of the Abeta1-40 sequence. Various systems differing in the customized beta-sheet
      breaker structure have been studied. Specifically we have considered three kinds
      of beta-sheet breakers, namely Ac-LPFFD-NH2 and two variants thereof, one
      obtained by substituting the acetyl group with the sulfonic amino acid taurine
      (Tau-LPFFD-NH2) and a second novel one in which the aspartic acid is substituted
      by an asparagine (Ac-LPFFN-NH2). Thioflavin T fluorescence, circular dichroism,
      and mass spectrometry experiments have been performed indicating that beta-sheet
      breakers are able to inhibit in vitro fibril formation and prevent the beta sheet
      folding of portions of the Abeta1-40 peptide. We show that molecular dynamics
      simulations and far UV circular dichroism provide consistent evidence that the
      new Ac-LPFFN-NH2 beta-sheet breaker is more effective than the other two in
      stabilizing the native alpha-helix structure of Abeta1-40. In agreement with
      these results thioflavin T fluorescence experiments confirm the higher efficiency
      in inhibiting Abeta1-40 aggregation. Furthermore, mass spectrometry data and
      molecular dynamics simulations consistently identified the 17-21 Abeta1-40
      portion as the location of the interaction region between peptide and the Ac
      LPFFN-NH2 beta-sheet breaker. 

PMID- 24584950
TI  - Acid sphingomyelinase, autophagy, and atherosclerosis.

PMID- 24584951
TI  - Upping the Reinforcement Rate by Playing the Maximum Lines in Multi-line Slot
      Machine Play.
AB  - Reinforcement is a key component of slot machine play. Multi-line video slot
      machine play can lead to "losses disguised as wins" (LDWs) which are credit gains
      that total less than the wager on the spin. LDWs only occur on multi-line games,
      with their frequency increasing with the number of lines played. If perceived as
      wins, they will be reinforcing to the player despite actually being losses. It
      has been suggested that players may attempt to maximize their reinforcement rates
      by playing maximum lines with a minimum bet per line. We recorded the actual game
      play of 83 participants on two different machines having different LDW rates. On
      both machines, players, regardless of problem gambling status, seldom bet on a
      single line (<6% of spins), preferring to bet on the maximum number of lines
      available (>70% of spins). Post-reinforcement pauses indicated that players found
      LDWs significantly more rewarding than losses and as rewarding as small wins.
      Players significantly overestimated the number of times they won more than their
      spin wager (i.e., miscategorizing LDWs as wins). Players indicated a number of
      game traits that made them prefer one machine over the other. Players who
      preferred the game with many LDWs endorsed "lack of long losing streaks" and
      "frequency of wins" to a greater degree than those preferring the other game. In
      sum, gamblers prefer playing maximum lines. Maximum line-play increases the
      frequency of LDWs. Players may miscategorize LDWs as wins, thus increasing the
      perceived reinforcement rate of multi-line slot machine.

PMID- 24584952
TI  - A Descriptive Study of Gambling Among Emerging Adult Males in French-Speaking
      Switzerland.
AB  - The aims were twofold: to examine the gambling habits of emerging adult males in
      the French-speaking regions of Switzerland and to what extent these habits
      predict problem gambling within this population. We also evaluated problem
      gambling rates and provided data concerning variables such as gambling location,
      level of information about problem gambling and awareness of treatment centers.
      606 Swiss male conscripts, aged 18-22 years, completed a self-report
      questionnaire. This was administered during their army recruitment day in 2012.
      Problem gambling was assessed through the Problem Gambling Severity Index (PGSI)
      (Ferris and Wynne 2001). 78.5% of the respondents were lifetime gamblers, 56.1%
      were past-year gamblers. Four out of ten past-year gamblers played in private
      spaces and in back rooms. The PGSI indicated that 10.8% of past-year gamblers
      presented with moderate gambling problems, whilst 1.4% appeared to be problem
      gamblers. The majority of respondents had never received information about
      problem gambling. Moreover, they were unaware of the existence of treatment
      centers for problem gambling in their region. PGSI scores were significantly
      predicted by the variety of games played. Problem gambling rates among young men
      appear to be higher than those of the general Swiss population. This confirms
      that emerging adult males are a particularly vulnerable population with regards
      to gambling addiction. The implications of this are considered for youth gambling
      prevention programs.

PMID- 24584939
TI  - Association of the breast cancer antiestrogen resistance protein 1 (BCAR1) and
      BCAR3 scaffolding proteins in cell signaling and antiestrogen resistance.
AB  - Most breast cancers are estrogen receptor-positive and treated with
      antiestrogens, but aberrant signaling networks can induce drug resistance. One of
      these networks involves the scaffolding protein BCAR1/p130CAS, which regulates
      cell growth and migration/invasion. A less investigated scaffolding protein that
      also confers antiestrogen resistance is the SH2 domain-containing protein BCAR3.
      BCAR1 and BCAR3 bind tightly to each other through their C-terminal domains, thus
      potentially connecting their associated signaling networks. However, recent
      studies using BCAR1 and BCAR3 interaction mutants concluded that association
      between the two proteins is not critical for many of their interrelated
      activities regulating breast cancer malignancy. We report that these previously
      used BCAR mutations fail to cause adequate loss-of-function of the complex. By
      using structure-based BCAR1 and BCAR3 mutants that lack the ability to interact,
      we show that BCAR3-induced antiestrogen resistance in MCF7 breast cancer cells
      critically depends on its ability to bind BCAR1. Interaction with BCAR3 increases
      the levels of phosphorylated BCAR1, ultimately potentiating BCAR1-dependent
      antiestrogen resistance. Furthermore, antiestrogen resistance in cells
      overexpressing BCAR1/BCAR3 correlates with increased ERK1/2 activity. Inhibiting
      ERK1/2 through overexpression of the regulatory protein PEA15 negates the
      resistance, revealing a key role for ERK1/2 in BCAR1/BCAR3-induced antiestrogen
      resistance. Reverse-phase protein array data show that PEA15 levels in invasive
      breast cancers correlate with patient survival, suggesting that PEA15 can
      override ERK1/2 activation by BCAR1/BCAR3 and other upstream regulators. We
      further uncovered that the BCAR3-related NSP3 can also promote antiestrogen
      resistance. Thus, strategies to disrupt BCAR1-BCAR3/NSP3 complexes and associated
      signaling networks could ultimately lead to new breast cancer therapies. 

PMID- 24584953
TI  - Effect of microwave heating on the quality characteristics of canola oil in
      presence of palm olein.
AB  - BACKGROUND: Microwave heating is one of the most attractive cooking methods for
      food preparation, commonly employed in households and especially in restaurants
      for its high speed and convenience. The chemical constituents of oils that
      degrade during microwave heating do so at rates that vary with heating
      temperature and time in a similar manner to other type of processing methods. The
      rate of quality characteristics of the oil depends on the fatty acid composition
      and the minor components during heating. Addition of oxidative-stable palm olein
      (PO) to heat sensitive canola oil (CO), may affect the quality characteristics of
      CO during microwave heating. The aim of this study was to evaluate how heat
      treatments by microwave oven affect the quality of CO in presence of PO. MATERIAL
      AND METHODS: The blend was prepared in the volume ratio of 40:60 (PO:CO, PC).
      Microwave heating test was performed for different periods (2, 4, 8, 12, 16 and
      20 min) at medium power setting for the samples of CO and PC. The changes in
      quality characteristics of the samples during heating were determined by
      analytical and instrumental methods. RESULTS: In this study, refractive index,
      free fatty acid content, peroxide value, p-anisidine value, TOTOX value, specific
      extinction, viscosity, polymer content, polar compounds and food oil sensor value
      of the oils all increased, whereas iodine value and C18.2 /C16:0 ratio decreased
      as microwave heating progressed. Based on the most oxidative stability criteria,
      PO addition led to a slower deterioration of CO at heating temperatures. The
      effect of microwave heating on the fatty acid composition of the samples was not
      remarkable. PO addition decelerated the formation of primary and secondary
      oxidation products in CO. However, effect of adding PO to CO on the formation of
      free fatty acids and polymers during microwave treatment was not significant (P <
      0.05). No significant difference in food oil sensor value was detected between CO
      and PC throughout the heating periods. CONCLUSION: Microwave heating caused
      formation of comparatively lower amounts of some degradative products in PC
      compared to CO indicating a lower extent of oxidative degradation of PC.

PMID- 24584954
TI  - Optimization of process parameters for microwave-vacuum puffing of black radish
      slices using the response surface method.
AB  - BACKGROUND: Due to the health-promoting value of black radish, authors decided to
      investigate the feasibility of forming - from its roots - chips, using the
      process of microwave-vacuum puffing. In order to produce desirable quality of
      chips, there is a need to determine the most advantageous values of process
      parameters. The main goal of the paper is to investigate the possibility of
      determining the best processing conditions for microwave-vacuum formation of
      black radish chips that can maximize the chips expansion ratio while maintaining
      consumer acceptability of sensory quality of chips. MATERIAL AND METHODS: The raw
      material for analyses comprised fresh roots of black radish {raphanns sativus
      linne varietas niger). A three-level, one-factor central composite experimental
      design (DOE) was applied. The response surface method (RSM) was used as a part of
      the Statistica software and the R computer program for optimization. Response
      surfaces were built using the second degree polynomial that includes principal
      effects of processing parameters values and their interactions. RESULTS: A
      regression model was derived, based on results of natural experiments, that give
      a satisfactory prediction level (R2 = 0.96) of the expansion ratio of black
      radish chips as a function of processing conditions. Then, the best values of
      process parameters were found using the RSM. The best processing parameters
      values were determined to be 0.39 kg kg-1 wb (wet basis) moisture content of pre
      dehydrated radish slices, 14.5 kPa vacuum absolute pressure and 80 s of microwave
      heating time during puffing (for the 650 W power output of the microwave
      generator). CONCLUSION: Optimized process of puffing of black radish slices using
      the RSM provided a satisfactory high value of the sensory quality index of chips.
      In this paper we do not analyze the physical structure of chips. In the future
      more research needs to be done in this area.

PMID- 24584955
TI  - Minerals and chosen heavy metals retention in immature common bean (Phaseolus
      vulgaris L.) seeds depending on the method of preservation.
AB  - BACKGROUND: Legumes are a good source of protein, and are also abundant in
      carbohydrates, B-group vita-mins, dietary fibre and mineral compounds. MATERIAL
      AND METHODS: This work evaluates the retention of ash, eleven minerals and two
      heavy metals in products obtained from two common bean cultivars harvested before
      reaching full maturity, with a dry matter content of about 40%. Analyses were
      conducted on raw, blanched and cooked seeds and three products prepared for
      consumption after 12-month storage: two frozen and one canned (sterilized). The
      former comprised two types of frozen product: one traditionally produced
      (blanching-freezing-frozen storage-cooking), the other a convenience, "ready-to
      eat" product obtained using a modified method (cooking-freezing-frozen storage
      defrosting-heating to consumption temperature in a microwave oven). RESULTS: In
      cooked bean seeds of both cultivars, levels of potassium, calcium, magnesium and
      copper were significantly lower, the only exception being the content of ash and
      sodium (due to added salt), than in blanched seeds; the changes in the remaining
      components were not so clear-cut and depended on the cultivar. Seeds frozen using
      the modified technology generally showed higher levels of the elements
      investigated than frozen products produced traditionally, with the exception of
      chromium, nickel and lead. Sterilized seeds had lower levels of ash, phosphorus,
      calcium, magnesium, iron, zinc, manganese, copper and chromium compared with both
      types of frozen product; retention levels of individual components depended on
      the cultivar examined. Conclusions. Compared with the traditionally produced
      frozen product, prepared for consumption, seeds after modified method of freezing
      (convenience food) contained significantly higher levels of ash and all
      macroelements, regardless of the cultivar. Seeds preserved by sterilization,
      compared with frozen seeds (either method of production) prepared for
      consumption, had lower content of most of the analyzed components.

PMID- 24584956
TI  - Ultrasonic monitoring of fish thawing process optimal time of thawing and
      effect of freezing/thawing.
AB  - INTRODUCTION: Fish quality is traditionally controlled by chemical and
      microbiological analysis. The non-destructive control presents an enormous
      professional interest thanks to the technical contribution and precision of the
      analysis to which it leads. This paper presents the results obtained from a
      characterisation of fish thaw-ing process by the ultrasonic technique, with
      monitoring thermal processing from frozen to defrosted states. MATERIAL AND
      METHODS: The study was carried out on fish type red drum and salmon cut into
      fillets of 15 mm thickness. After being frozen at -20 degrees C, the sample is
      enclosed in a plexiglas vessel with parallel walls at the ambient temperature 30
      degrees C and excited in perpendicular incidence at 0.5 MHz by an ultrasonic
      pulser-receiver Sofranel 5052PR. the technique of measurement consists to study
      the signals reflected by fish during its thawing, the specific techniques of
      signal processing are implemented to deduce informations characterizing the state
      of fish and its thawing process by examining the evolution of the position echoes
      reflected by the sample and the viscoelastic parameters of fish during its
      thawing. RESULTS: The obtained results show a relationship between the thermal
      state of fish and its acoustic properties, which allowed to deduce the optimal
      time of the first thawing in order to restrict the growth of microbial flora. For
      salmon, the results show a decrease of 36% of the time of the second thawing and
      an increase of 10.88% of the phase velocity, with a decrease of 65.5% of the peak
      to-peak voltage of the signal reflected, thus a decrease of the acoustic
      impedance. CONCLUSIONS: This study shows an optimal time and an evolution rate of
      thawing specific to each type offish and a correlation between the acoustic
      behavior of fish and its thermal state which approves that this technique of
      ultrasonic monitoring can substitute the control using the destructive chemical
      analysis in order to monitor the thawing process and to know whether a fish has
      suffered an accidental thawing.

PMID- 24584957
TI  - Variation in antioxidant and antimicrobial activities in Lantana camara L.
      flowers in relation to extraction methods.
AB  - BACKGROUND: The present work was designed to appraise how different extraction
      solvents and techniques affect the extractability of antioxidant and
      antimicrobial components from Lantana camara (L. camard) flowers. MATERIAL AND
      METHODS: Four extraction solvents including 100% methanol, 80% methanol, 100%
      ethanol and 80% ethanol coupled with three extraction techniques namely stirring,
      microwave-assisted stirring and ultrasonic-assisted stirring employed to isolate
      extractable components from the flowers of L. camara. The extracts produced were
      evaluated for their antioxidant and antimicrobial attributes. RESULTS AND
      DISCUSSION: The yield of extractable components varied over a wide range 4.87
      30.00% in relation to extraction solvent and techniques. The extracts produced
      contained considerable amounts of total phenolics (8.28-52.34 mg GAE/100 g DW)
      and total flavonoids (1.24-7.88 mg CE/100 g DW). Furthermore, a promising
      antioxidant activity in terms of DPPH degrees  scavenging, inhibition of linoleic
      acid peroxidation and reducing power, as well as antimicrobial potential of the
      extracts were recorded against the selected bacterial and fungal strains.
      CONCLUSIONS: It was concluded that both extraction solvent and techniques
      employed affected the antioxidant and antimicrobial attributes of the extracts
      from L. camara flowers. With few exceptions, overall methanolic extracts produced
      by ultrasonic-assisted stirring offered superior activities followed by the
      microwave-assisted stirring and then stirring. The results advocate the use of
      appropriate extraction strategies to recover potent antioxidant and antimicrobial
      agents from the flowers of L. camara for nutraceutical and therapeutic.

PMID- 24584958
TI  - Preparation of lactic acid bacteria fermented wheat-yoghurt mixtures.
AB  - BACKGROUND: Tarhana, a wheat-yoghurt fermented mixture, is considered as a good
      source of saccharides, proteins, some vitamins and minerals. Moreover, their
      preparation is inexpensive and lactic acid fermentation offers benefits like
      product preservation, enhancement of nutritive value and sensory properties
      improvement. The aim of this work was to evaluate changes of some chemical
      parameters during fermentation of tarhana, when the level of salt and amount of
      yoghurt used were varied. Some functional and sensory characteristics of the fi
      nal product were also determined. MATERIAL AND METHODS: Chemical analysis
      included determination of pH, titrable acidity, content of reducing saccharides,
      lactic, acetic and citric acid. Measured functional properties of tarhana powder
      were foaming capacity, foam stability, water absorption capacity, oil absorption
      capacity and emulsifying activity. Tarhana soups samples were evaluated for their
      sensory characteristics (colour, odor, taste, consistency and overall
      acceptability). RESULTS: Fermentation of tarhana by lactic acid bacteria and
      yeasts led to decrease in pH, content of reducing saccharides and citric acid,
      while titrable acidity and concentration of lactic and acetic acid increased.
      Determination of functional properties of tarhana powder showed, that salt
      absence and increased amount of yoghurt in tarhana recipe reduced foaming
      capacity and oil absorption capacity, whereas foam stability and water absorption
      capacity were improved. Sensory evaluation of tarhana soups showed that
      variations in tarhana recipe adversly affected sensory parameters of fi nal
      products. CONCLUSION: Variations in tarhana recipe (salt absence, increased
      proportion of yoghurt) led to changes in some chemical parameters (pH, titrable
      acidity, reducing saccharides, content of lactic, acetic and citric acid).
      Functional properties were also affected with changed tarhana recipe. Sensory
      characteristics determination showed, that standard tarhana fermented for 144 h
      had the highest overall acceptability.

PMID- 24584959
TI  - Cow's milk quality and energy value during different lactation stages.
AB  - BACKGROUND: The quality of dairy products, raw milk in particular, depends on
      many factors. Low bacterial and somatic cell counts are basic determinants of the
      appropriate raw milk quality. The objective of the work was to assess the effect
      of selected factors, that is, the age of cows and their daily milk performance,
      on cytological quality (somatic cell count) and energy value of milk produced at
      individual stages of lactation. MATERIAL AND METHODS: Somatic cell count and
      energy value of cow's milk were assessed. A total of 229 792 milk samples were
      examined. Data for analysis were taken from milk records of 350 dairy herds.
      RESULTS: It was demonstrated that, of all the lactations studied, the fi rst
      lactation (from calving to the 100th day of lactation) was characterised by the
      highest daily milk performance (25.1 kg) and the lowest somatic cell count (356
      thous./1 ml), fat, protein and dry matter contents (4.06, 2.96 and 12.41%,
      respectively) and milk calorific value (732 kcal/kg). The highest energy value
      was recorded in cow's milk produced towards the end of lactation, that is from
      day 300 till the end of lactation (842 kcal/kg). CONCLUSIONS: High milk calorific
      value in late lactation and high fat and protein contents were accompanied by low
      raw milk quality.

PMID- 24584960
TI  - Association of vegan diet with RMR, body composition and oxidative stress.
AB  - BACKGROUND: There is increasing evidence to suggest that a vegetarian diet low in
      fat and high in complex carbohydrates offers the potential for decreasing the
      risk of chronic disease. However, there is little information about the effect of
      vegetarian diets on resting metabolic rate (RMR). The objective of this study was
      to determine the association of vegan diet with RMR and body composition and
      oxidative stress. MATERIAL AND METHODOLOGY: This research is a cross-sectional
      descriptive analytic study in which two groups of vegetarians and non vegetarians
      were compared. RMR was determined by indirect calorimetry, the amount of body fat
      mass (FM), the percentage of free fat mass (FFM), the markers of oxidative stress
      (MAD), poteins (PCO) and total anti-oxidatant capacity were measured in 20
      vegetarians and 20 non-vegetarians. The two groups were matched with regard to
      body mass index, sex and menstrual cycle. Energy and macronutrient intakes were
      determined using a 3-day food record and body composition was determined by
      bioelectric impedance. RESULTS: VEG reported a lower relative intake of protein
      (40.45 +/- 19.41 g, 56.96 +/- 11.94 g, p = 0.04), whereas no differences were
      observed in daily energy, carbohydrate or fat intakes and body composition. NVEG
      exhibited a higher absolute RMR (1354.7 +/- 192.6, 1569.10 +/- 348.24 Kcal/24 h,
      p = 0.02). PCO plasma density was seen significantly higher among non-vegetarians
      (1.09 +/- 3.6, 0.81 +/- 0.42, p = 0.02). No significant differences were seen in
      plasma density of TAC between two groups and MAD was higher amoung vegetarians.
      CONCLUSION: These results suggest that the lower RMR observed in VEG is partially
      mediated by differences in dietary macronutrient composition.

PMID- 24584961
TI  - Nutritional status and nutritional habits of men with benign prostatic
      hyperplasia or prostate cancer - preliminary investigation.
AB  - INTRODUCTION: The ageing in men, the most frequent pathologic lesions affecting
      the prostatic gland in this period are benign prostatic hyperplasia (BPH) and
      prostate cancer (PC), the course of which may be influenced by the improper
      nutritional status of patients and their nutritional habits. The aim of this
      study was, therefore, to evaluate the nutritional status and eating habits of men
      diagnosed and treated for one of the above diseases. MATERIAL AND METODS: The
      nutritional status of 30 male patients with clinically confirmed and treated
      disease of the prostatic gland, including 15 men (aged 51-75 years) with BPH and
      15 men (aged 51-73 years) with PC, was evaluated based on their BMI, WC, WHR, and
      WHtR parameters. In turn, the energy and nutritive value of 90 daily food rations
      (DFRs) was evaluated. Finally, calculations were made for the Key's index of diet
      atherogenicity, resultant Glycemic Index (GI) and Glycemic Load (GL). RESULTS:
      Higher values of the BMI, WC, WHR and WHtR parameters were noted in the men with
      PC, they were also characterized by a higher incidence of peripheral subcutaneous
      obesity and visceral obesity. The DFRs of the men were characterized by a low
      energy value and by a low intake of available carbohydrates, dietary fi ber, K,
      Ca, Mg, vitamins D and C, and fl uids at a simultaneously high intake of total
      and animal protein, cholesterol, Na, P, Fe, Cu as well as vitamins B2 and PP. The
      contribution of energy derived from the basic nutrients diverged from the
      recommended values. In addition, the DFRs were characterized by high values of
      Key's index and 24-h GL. Differences in meeting the RDA for selected nutrients
      between the analysed groups of men were statistically significant. CONCLUSIONS:
      The improper nutritional status of the men may result from their incorrect
      nutritional habits which fail to improve their health status, and even predispose
      them to the development of some diet-dependent diseases. In view of that, both
      correction of diets of the surveyed men, as well as their health-promoting
      nutritional education in the aspect of prostate diseases seem necessary.

PMID- 24584962
TI  - Concentration of selected trace elements in Xerocomus badius mushroom bodies - a
      health risk for humans?
AB  - INTRODUCTION: As regards a significant intake of wild growing edible mushrooms,
      especially in East and Central Europe, concentrations of toxic elements should be
      periodically analysed. The aim of the study was to assess changes in
      concentrations of selected trace elements (Ba, Cd, Co, Cu, Fe, Hg, Mn, Ni, Pb, Sr
      and Zn) in a mushroom species, Xerocomus badius. MATERIAL AND METHODS: Xerocomus
      badius fruiting bodies were collected from fi ve regions of Poland within the
      last 20 years (selected years when these mushrooms were growing). Flame atomic
      absorption spectrometry (FAAS) was used for determination of 10 elements while
      for Hg cold vapour atomic absorption spectrometry (CVAAS) was used. RESULTS:
      Generally the results show no significant differences in the accumulation
      efficiency of individual elements by mushrooms collected from different regions
      of Poland, but significant differences were observed in the accumulation
      efficiency of these elements by mushrooms collected in particular years of their
      harvest. The highest accumulation indicated by bioconcentration factors (BCFs)
      was observed for Cu (10.03), Hg (148.15) and Zn (4.88). CONCLUSION:
      Concentrations of Cu, Fe, Mn, Zn in the tested mushrooms were found to be lower
      than the values of the recommended dietary allowances (RDA), therefore the levels
      of these elements are not toxic for people. In our opinion, occasional
      consumption of these mushroom fruiting bodies within the last 20 years in Poland
      did not provide significant amounts of analysed trace elements (no more than
      other foods).

PMID- 24584963
TI  - alpha-Haloacrylates as acceptors in the [3 + 2] cycloaddition reaction with NaN3:
      an expedient approach to N-unsubstituted 1,2,3-triazole-4-carboxylates.
AB  - An expedient synthesis of N-unsubstituted 1,2,3-triazole-4-carboxylates has been
      demonstrated through [3 + 2] cycloaddition of sodium azide with alpha
      haloacrylates. The process is highly reliable and exhibits an unusually wide
      scope with respect to alpha-fluoro-, alpha-chloro-, alpha-bromo-, and alpha
      iodoacrylates. The potential of selected 1,2,3-triazole-4-carboxylates in the
      preparation of 1,5-dihydro-4H-[1,2,3]-triazolo-[4,5-c]-quinolin-4-one has also
      been illustrated. 

PMID- 24584969
TI  - Cyclic dipeptide immobilization on Au(111) and Cu(110) surfaces.
AB  - Soft X-ray Photoelectron Spectroscopy (XPS) and Near Edge X-ray Absorption Fine
      Structure (NEXAFS) spectroscopy have been used to probe the electronic and
      adsorption properties of two cyclic dipeptides, i.e. cyclo(glycyl-histidyl) and
      cyclo(phenylalanyl-prolyl), on Au(111) and Cu(110) surfaces. The core level
      spectra show chemical shifts which indicate weak chemisorption on Au(111), and
      stronger chemisorption on the Cu(110) surface, mainly via one of the nitrogen
      atoms in the central rings of both molecules, and nitrogen in the imidazole ring
      of cyclo(glycyl-histidyl). From the angular dependence of the NEXAFS spectra at
      the O and N K-edges, we conclude that both dipeptides have a preferred
      orientation on the two surfaces. 

PMID- 24584971
TI  - A database of whole-body action videos for the study of action, emotion, and
      untrustworthiness.
AB  - We present a database of high-definition (HD) videos for the study of traits
      inferred from whole-body actions. Twenty-nine actors (19 female) were filmed
      performing different actions-walking, picking up a box, putting down a box,
      jumping, sitting down, and standing and acting-while conveying different traits,
      including four emotions (anger, fear, happiness, sadness), untrustworthiness, and
      neutral, where no specific trait was conveyed. For the actions conveying the four
      emotions and untrustworthiness, the actions were filmed multiple times, with the
      actor conveying the traits with different levels of intensity. In total, we made
      2,783 action videos (in both two-dimensional and three-dimensional format), each
      lasting 7 s with a frame rate of 50 fps. All videos were filmed in a green-screen
      studio in order to isolate the action information from all contextual detail and
      to provide a flexible stimulus set for future use. In order to validate the
      traits conveyed by each action, we asked participants to rate each of the actions
      corresponding to the trait that the actor portrayed in the two-dimensional
      videos. To provide a useful database of stimuli of multiple actions conveying
      multiple traits, each video name contains information on the gender of the actor,
      the action executed, the trait conveyed, and the rating of its perceived
      intensity. All videos can be downloaded free at the following address: http://www
      users.york.ac.uk/~neb506/databases.html. We discuss potential uses for the
      database in the analysis of the perception of whole-body actions.

PMID- 24584970
TI  - The neurotransmitter glutamate and human T cells: glutamate receptors and
      glutamate-induced direct and potent effects on normal human T cells, cancerous
      human leukemia and lymphoma T cells, and autoimmune human T cells.
AB  - Glutamate is the most important excitatory neurotransmitter of the nervous
      system, critically needed for the brain's development and function. Glutamate has
      also a signaling role in peripheral organs. Herein, we discuss glutamate
      receptors (GluRs) and glutamate-induced direct effects on human T cells. T cells
      are the most important cells of the adaptive immune system, crucially needed for
      eradication of all infectious organisms and cancer. Normal, cancer and autoimmune
      human T cells express functional ionotropic and metabotropic GluRs. Different
      GluR subtypes are expressed in different T cell subtypes, and in resting vs.
      activated T cells. Glutamate by itself, at low physiological 10(-8)M to 10(-5)M
      concentrations and via its several types of GluRs, activates many key T cell
      functions in normal human T cells, among them adhesion, migration, proliferation,
      intracellular Ca(2+) fluxes, outward K(+) currents and more. Glutamate also
      protects activated T cells from antigen-induced apoptotic cell death. By doing
      all that, glutamate can improve substantially the function and survival of
      resting and activated human T cells. Yet, glutamate's direct effects on T cells
      depend dramatically on its concentration and might be inhibitory at excess
      pathological 10(-3)M glutamate concentrations. The effects of glutamate on T
      cells also depend on the specific GluRs types expressed on the target T cells,
      the T cell's type and subtype, the T cell's resting or activated state, and the
      presence or absence of other simultaneous stimuli besides glutamate. Glutamate
      also seems to play an active role in T cell diseases. For example, glutamate at
      several concentrations induces or enhances significantly very important functions
      of human T-leukemia and T-lymphoma cells, among them adhesion to the
      extracellular matrix, migration, in vivo engraftment into solid organs, and the
      production and secretion of the cancer-associated matrix metalloproteinase MMP-9
      and its inducer CD147. Glutamate induces all these effects via activation of
      GluRs highly expressed in human T-leukemia and T-lymphoma cells. Glutamate also
      affects T cell-mediated autoimmune diseases. With regards to multiple sclerosis
      (MS), GluR3 is highly expressed in T cells of MS patients, and upregulated
      significantly during relapse and when there is neurological evidence of disease
      activity. Moreover, glutamate or AMPA (10(-8)M to 10(-5)M) enhances the
      proliferation of autoreactive T cells of MS patients in response to myelin
      proteins. Thus, glutamate may play an active role in MS. Glutamate and its
      receptors also seem to be involved in autoimmune rheumatoid arthritis and
      systemic lupus erythematosus. Finally, T cells can produce and release glutamate
      that in turn affects other cells, and during the contact between T cells and
      dendritic cells, the latter cells release glutamate that has potent effects on
      the T cells. Together, these evidences show that glutamate has very potent
      effects on normal, and also on cancer and autoimmune pathological T cells.
      Moreover, these evidences suggest that glutamate and glutamate-receptor agonists
      might be used for inducing and boosting beneficial T cell functions, for example,
      T cell activity against cancer and infectious organisms, and that glutamate
      receptor antagonists might be used for preventing glutamate-induced activating
      effects on detrimental autoimmune and cancerous T cells. 

PMID- 24584973
TI  - Invasive carcinoma arising from sclerosing polycystic adenosis of the salivary
      gland.
AB  - Sclerosing polycystic adenosis is a rare salivary gland lesion. Recently, this
      entity has been regarded as a neoplastic lesion of low-grade malignant potential
      but, to date, no invasive carcinoma, metastases, or associated mortality have
      been reported. We report the first case of an invasive carcinoma component in a
      recurrent sclerosing polycystic adenosis lesion. 

PMID- 24584974
TI  - A new bright-field dual-colour chromogenic and silver in situ hybridization
      method for the detection of FGFR1 gene copy number status.
AB  - Recently, the fibroblast growth factor receptor 1 (FGFR1) has been identified as
      the first actionable target in squamous cell lung cancer. Clinical trials testing
      specific FGFR inhibitors are in progress, and patients are selected based on
      their FGFR1 gene copy number status. Fluorescent in situ hybridization is the
      most commonly used method for detecting FGFR1 amplifications, but it has its
      limitations. In this paper, we describe a new non-fading and easy to assess assay
      for detecting FGFR1 amplification using a combination of chromogenic and silver
      in situ hybridization. We assessed 394 patients diagnosed with head and neck
      squamous cell carcinoma with the new assay and compared the results with those
      obtained by FGFR1 fluorescent in situ hybridization. We could assess copy number
      by the fluorescent in situ hybridization in 86.8 % (342/394) of cases, whereas
      with chromogenic and silver in situ hybridization, this was 79.4 % (313/394). By
      fluorescent in situ hybridization, a FGFR1 amplification was detected in 12.6 %
      (43/342) of cases, a low-level amplification (LLA) in 7.6 % (26/342) and a high
      level amplification (HLA) in 5.0 % (17/342). By chromogenic and silver in situ
      hybridization, a FGFR1 amplification was found in 10.2 % (32/313) (5.7 % LLA, 4.5
      % HLA). The two techniques showed highly concordant results (Pearson's
      correlation coefficient = 0.971, p < 0.01).

PMID- 24584975
TI  - The development and implementation of a direct admission system at a tertiary
      care hospital.

PMID- 24584976
TI  - Do we need this blood culture?
AB  - OBJECTIVES: This study describes blood culture collection rates, results, and
      microbiology laboratory charges for 4 leading pediatric inpatient diagnoses
      (asthma, bronchiolitis, pneumonia, and skin and soft tissue infection [SSTI]) in
      low-risk patients. METHODS: This retrospective cohort study was conducted at an
      urban, academic, quaternary children's hospital. The study period was from
      January 1, 2011, to December 31, 2011. Inclusion criteria were as follows: 6
      months to 18 years of age and primary diagnosis of asthma (International
      Classification of Diseases, Ninth Revision [ICD-9] codes 493.91-493.92),
      bronchiolitis (ICD-9 codes 466.11 and 466.19), SSTI (ICD-9 codes 680.00-686.99),
      or pneumonia (community-acquired pneumonia; ICD-9 codes 481.00-486.00). Patients
      with complex chronic conditions were excluded. Data were collected via
      administrative billing data and chart review. Descriptive statistics were
      performed; chi(2) tests were used for categorical variables, and nonparametric
      tests were used for continuous variables because of non-normal distributions.
      RESULTS: Administrative data review included 5159 encounters, with 1629 (32%)
      inpatient encounters and 3530 (68%) emergency department/outpatient encounters.
      Twenty-one percent (n = 343) of inpatient encounters had blood cultures
      performed, whereas 3% (n = 111) of emergency department/outpatient encounters had
      blood culture testing performed. Inpatient blood culture utilization varied
      according to diagnosis: asthma, 4%; bronchiolitis, 15%; pneumonia, 36%; and SSTI,
      46%. Charts were reviewed for all 343 inpatients with blood culture testing.
      Results of all the blood cultures obtained for asthma and bronchiolitis
      admissions were negative, with 98% and 99% negative or false-positive
      (contaminant) for SSTI and community-acquired pneumonia, respectively. The
      approximate financial impact of blood culture utilization (according to gross
      microbiology laboratory charges) approximated $100 000 over the year for all 4
      diagnoses. CONCLUSIONS: There was a high rate of negative or false-positive blood
      culture results for these common inpatient diagnoses. In addition, there was a
      low rate of clinically significant true-positive (pathogenic) culture results.
      These results identify points of potential blood culture overutilization.

PMID- 24584977
TI  - The never-ending quest to detect bacteremia: time for a culture change.

PMID- 24584978
TI  - Inpatient hospitalizations for croup.
AB  - OBJECTIVES: Croup is a common childhood respiratory illness that can result in
      hospitalization and significant morbidity. This study reviewed records of
      patients hospitalized with croup to determine characteristics associated with
      increased inpatient treatment and length of stay (LOS). METHODS: Eligible
      patients were admitted between January 2006 and December 2010 and had discharge
      diagnosis of croup. Patients were included if they received either racemic
      epinephrine or systemic corticosteroids during their emergency department or
      hospital treatment. Patients were excluded for incomplete data on medication or
      vital signs timing. Hospitalization and treatment decisions were at the
      discretion of the treating physician. RESULTS: The study analyzed 365
      hospitalizations involving 327 patients, 72% male, 62% white, with median age of
      16.7 months. Median LOS was 31.7 hours. Patients required racemic epinephrine
      treatments after hospitalization in 179 cases (49%; mean, 1.33 treatments; range,
      0-13; median, 0), and 176 patients (48%) received a dose of systemic
      corticosteroids after hospital admission. Patients who required racemic
      epinephrine treatments after hospitalization were indistinguishable from those
      who did not, based on demographics, past history, or presenting vital signs.
      Patients with history of croup, history of intubation, or with oxygen saturation
      <95% on presentation all had increased LOS compared with those without these
      findings (P < .05). CONCLUSIONS: Fifty-one percent of patients hospitalized with
      croup did not require inpatient racemic epinephrine treatments. Those with lower
      oxygen saturations on presentation or past history of croup or intubation were
      more likely to have prolonged or complicated hospital course.

PMID- 24584979
TI  - Characterizing the adequacy, effectiveness, and barriers related to research
      mentorship among junior pediatric hospitalists and general pediatricians at a
      large academic institution.
AB  - OBJECTIVE: The purpose of this qualitative study was to characterize the
      adequacy, effectiveness, and barriers related to research mentorship among junior
      pediatric hospitalists and general pediatricians at a large academic institution.
      METHODS: Junior faculty and staff physicians in hospital medicine and general
      pediatrics at a large academic institution were invited to participate in this
      qualitative study. In-depth interviews were conducted. Experienced mentors were
      invited to be interviewed for theoretical sampling. Interviews were conducted and
      analyzed by using grounded theory methodology. RESULTS: Twenty-six (75%) of the
      eligible physicians, pediatric hospitalists representing 65% of this sample,
      agreed to be interviewed about their mentoring experiences. Satisfied and
      dissatisfied participants expressed similar mentoring themes: acquisition of
      research skills, academic productivity, and career development. Four experienced
      mentors were interviewed and provided rationale for mentoring clinicians in
      research. Both groups of participants agreed that institutional support is vital
      for promoting mentorship. CONCLUSIONS: Junior pediatric hospitalists and general
      pediatricians indicated considerable interest in being mentored to learn to do
      clinical research. Developing faculty and staff physicians to their utmost
      potential is critical for advancement in academic medicine. Mentoring clinical
      physicians seeking to add research skills and academic productivity to their
      practice merits study as an innovative path to develop clinical investigators.
      Hospital medicine, as a rapidly developing pediatric specialty, is well
      positioned to implement the necessary infrastructure to mentor junior faculty in
      their academic pursuits, thereby optimizing the potential impact for individuals,
      families, learners, and institutions.

PMID- 24584980
TI  - Patient characteristics and disposition after pediatric medical emergency team
      (MET) activation: disposition depends on who activates the team.
AB  - OBJECTIVES: This study focused on health care staff (HCS) responsible for
      activating the medical emergency team (MET) at a pediatric tertiary hospital
      using a well-established rapid response system. Our goals were to report the
      patient characteristics, MET interventions, and disposition by activating HCS.
      METHODS: This is a retrospective cohort study of pediatric patients who received
      MET activation at the Children's Hospital of Eastern Ontario in Ottawa, Canada.
      Data were obtained from a prospectively maintained rapid response system
      database. The primary outcome was PICU admission, with the number and type of
      interventions performed as secondary outcomes. RESULTS: The most common MET
      activators were physicians (410, 53.3%) with nurses generating a comparable
      number (367, 47.7%). Significant differences in PICU admission rates were
      observed between activator groups, with physicians having statistically higher
      PICU admission rates when compared with nurses (25.2% vs 15.0%, P = .001).
      Compared with physicians, nursing-led activations on surgical patients had
      significantly lower odds of PICU admission relative to medical patients (odds
      ratio 0.19 vs 0.67; P = .03). No significant difference was observed in the type
      or number of interventions between any subgroup based on patient (surgery vs
      medical) or activator type. CONCLUSIONS: This study suggests that when nurses
      activate MET, patients are less likely to be transferred to the PICU despite
      receiving similar type and number of interventions. Our study results may help
      direct education initiatives aimed at enhancing the effectiveness of the afferent
      limb through informing specific HCS as to the importance of their role in using
      the MET.

PMID- 24584981
TI  - On target: a case of acute hemorrhagic edema of infancy.

PMID- 24584982
TI  - Hospitalists should have increased suspicion for primary ciliary dyskinesia in
      patients with congenital heart disease.

PMID- 24584984
TI  - Making an omelet.

PMID- 24584985
TI  - The power of a laboratory--are we taking full ownership as hospitalists?

PMID- 24584988
TI  - Adding evidence-based interventions to assertive community treatment: a
      feasibility study.
AB  - OBJECTIVE: This 24-month study, conducted in The Netherlands, examined the
      feasibility of enhancing the effectiveness of assertive community treatment (ACT)
      by adding evidence-based interventions. METHODS: A total of 159 patients were
      randomly assigned to two ACT teams, one providing standard ACT (N585) and an ACT
      Plus team that also provided evidence-based interventions (N574):
      psychoeducation, family interventions, individual placement and support, and
      cognitive behavioral therapy. The interventions were conducted by psychologists
      and nurse practitioners working independently from the ACT team. RESULTS:
      Although most patients were judged eligible for each of the four interventions
      (range 65% to 89%), only 12 of the 74 patients (16%) successfully completed an
      intervention. Outcomes, such as use of inpatient care, for ACT Plus and standard
      ACT patients did not differ significantly. CONCLUSIONS: Guidelines for the
      treatment of schizophrenia should consider the feasibility of delivering evidence
      based interventions to difficult-to-engage patients.

PMID- 24584987
TI  - Metallothionein and stress combine to affect multiple organ systems.
AB  - Metallothioneins (MTs) are a family of low molecular weight, cysteine-rich, metal
      binding proteins that have a wide range of functions in cellular homeostasis and
      immunity. MTs can be induced by a variety of conditions including metals,
      glucocorticoids, endotoxin, acute phase cytokines, stress, and irradiation. In
      addition to their important immunomodulatory functions, MTs can protect essential
      cellular compartments from toxicants, serve as a reservoir of essential heavy
      metals, and regulate cellular redox potential. Many of the roles of MTs in the
      neuroinflammation, intestinal inflammation, and stress response have been
      investigated and were the subject of a session at the 6th International Congress
      on Stress Proteins in Biology and Medicine in Sheffield, UK. Like the rest of the
      cell stress response, there are therapeutic opportunities that arise from an
      understanding of MTs, and these proteins also provide potential insights into the
      world of the heat shock protein.

PMID- 24584995
TI  - The successful management of dabigatran-associated critical end-organ bleeding
      with recombinant factor VIIa.

PMID- 24584997
TI  - Efficacy and safety of intravenous colistin in preterm infants with nosocomial
      sepsis caused by Acinetobacter baumannii.
AB  - OBJECTIVES: To describe the efficacy of intravenous colistin on clinical and
      microbiological outcomes in preterm infants with nosocomial sepsis in neonatal
      intensive care unit (NICU) and define adverse events observed with this
      treatment. METHODS: The records of preterm infants who received colistin with or
      without positive cultures in the NICU were retrospectively reviewed. Patients
      were evaluated for response to therapy and side effects. RESULTS: A total of 21
      preterm infants with medians of 28 weeks (23-36) gestational age and 870 g (620
      2,650) birth weight were included. The median duration and dose of colistin
      therapy were 9 days (3-26) and 3 mg/kg/d (2-5). Recovery rate in patients
      including all with/without positive culture was 81% (17/21). Microbiological
      clearance by colistin was 69% (9/13). The major side effect observed was acute
      kidney injury (19%). At least 24% of infants required electrolyte supplementation
      during the colistin therapy. Magnesium levels were significantly lower at the end
      of the colistin therapy (p < 0.001). Acute kidney injury and electrolyte
      disturbances including hypomagnesemia were reversible in all surviving patients.
      CONCLUSION: We suggest that renal function tests and serum electrolytes should be
      monitored closely and replaced in case of any need during the colistin therapy in
      preterm infants.

PMID- 24584998
TI  - Efficacy of prophylactic fluconazole therapy in decreasing the incidence of
      Candida infections in extremely low birth weight preterm infants.
AB  - OBJECTIVE: Systemic fungal infections are major causes of morbidity and
      mortality, and are associated with significant neurodevelopmental impairment in
      premature infants. Our objective was to evaluate the efficacy of fluconazole
      prophylaxis in prevention of systemic fungal infections among preterm infants.
      STUDY DESIGN: This observational pre-post cohort study was performed in preterm
      infants with a birth weight of < 1,000 g who were given prophylactic fluconazole
      starting on the first postnatal day at a dose of 3 mg/kg twice a week. These
      infants were compared with preterm infants who were not given prophylaxis.
      RESULTS: Prophylaxis group consisted of 90 infants and control group consisted of
      107 infants. Systemic fungal infection was observed in five patients (4.7%) in
      the control group while no fungal infection was detected in the prophylaxis group
      (p = 0.03). There were no significant differences between two groups in terms of
      demographic features, maternal and neonatal risk factors, and all-cause mortality
      rates. No adverse reactions were seen during the prophylaxis period. CONCLUSIONS:
      We suggest that intravenous fluconazole prophylaxis at a dose of 3 mg/kg twice a
      week is a safe and effective strategy for decreasing systemic fungal infections
      even in neonatal intensive care units with low rates of invasive Candida
      infection.

PMID- 24584999
TI  - Neonatal resuscitation using a nasal cannula: a single-center experience.
AB  - OBJECTIVE: The aim of the study was to describe our experience using a modified
      nasal cannula to deliver nasal continuous positive airway pressure and/or nasal
      intermittent positive pressure ventilation during primary neonatal resuscitation
      of preterm and term newborns. STUDY DESIGN: Data were collected retrospectively
      for all neonates resuscitated with nasal cannula in the delivery room. The
      primary outcome was the number of newborns intubated in the delivery room.
      Secondary outcomes included need for chest compressions, intubations in the first
      24 hours, air-leaks, and surfactant administration. RESULTS: A total of 102
      infants were resuscitated using nasal cannula. Eight (7.8%) were intubated in the
      delivery room, five (4.9%) required chest compressions, and five (4.9%) had
      pneumothorax noted on chest X-ray. No deaths occurred in the delivery room.
      Twenty-eight patients (27.5%) received early rescue surfactant after admission to
      the neonatal intensive care unit. CONCLUSION: Neonatal resuscitation can be
      effectively performed in preterm and term newborns using a modified nasal cannula
      in the delivery room.

PMID- 24585000
TI  - Higher-dose oxytocin to prevent obstetric hemorrhage at vaginal delivery-does
      duration of infusion matter?
AB  - OBJECTIVE: Postpartum higher-dose oxytocin (80 U) compared with lower dose (10 U)
      given in 500 mL over 1 hour does not decrease postpartum hemorrhage (PPH)
      requiring treatment, but reduces the risk of hematocrit decline >= 6% among women
      delivering vaginally. Our objective was to evaluate whether the duration of
      administration of oxytocin influences outcomes. STUDY DESIGN: We compared a
      cohort receiving a postpartum oxytocin infusion of 80 U/500 mL over 1 hour to a
      concurrent cohort of women receiving 80 U/500 mL over 8 hours. The primary
      outcome was any treatment of PPH (uterotonics, blood transfusion, tamponade, and
      surgery). Secondary outcomes included pre- to postdelivery median hematocrit
      change and hematocrit decline >= 6%. RESULTS: There were 653 and 676 women
      identified in the 1- and 8-hour cohorts, respectively. There was no difference in
      PPH requiring any treatment between the 1- and 8-hour cohorts (6 vs. 6%, p =
      0.70). There were no differences in individual treatment components including
      blood transfusion (p = 0.75). Median hematocrit decline (p = 0.02) was lower in
      the 8-hour cohort, but there was no difference in frequency of hematocrit decline
      >= 6% (p = 0.15). Results were unchanged by multivariable adjustments.
      CONCLUSIONS: Postpartum higher-dose oxytocin administered over 1 hour compared
      with 8 hours was not associated with an increased treatment of PPH or frequency
      of hematocrit decline >= 6%.

PMID- 24585001
TI  - Potential improvement of pregnancy outcome through prenatal small for gestational
      age detection. [correction].
AB  - OBJECTIVE: To assess differences in mode of delivery and pregnancy outcome
      between prenatally detected and nonprenatally detected small for gestational age
      (SGA) neonates born at term. STUDY DESIGN: We performed a retrospective
      multicenter cohort study. All singleton infants, born SGA in cephalic position
      between 36(0/7) and 41(0/7) weeks gestation, were classified as either prenatally
      detected SGA or nonprenatally detected SGA. With propensity score matching we
      created groups with comparable baseline characteristics. We compared these groups
      for composite adverse perinatal outcome, labor induction, and cesarean section
      rates. RESULTS: We included 718 SGA infants, of whom 555 (77%) were not
      prenatally detected. Composite adverse neonatal outcome did not differ
      statistically significant between the matched prenatally detected and the
      nonprenatally detected group (5.5 vs. 7.4%, odds ratio [OR] 0.74, 95% confidence
      interval [CI]: 0.30-1.8). However, perinatal mortality only occurred in the
      nonprenatally detected group (1.8% [3/163] in the matched cohort, 1.3% [7/555] in
      the complete cohort). In the propensity matched prenatally detected SGA group
      both induction of labor (57 vs. 9%, OR 14.0, 95% CI: 7.4-26.2) and cesarean
      sections (20 vs. 8%, OR 2.9, 95% CI: 1.5-5.8) were more often performed compared
      with the nonprenatally detected SGA group. CONCLUSION: Prenatal SGA detection at
      term allows timely induction of labor and cesarean sections thus potentially
      preventing stillbirth.

PMID- 24585002
TI  - Evolutionary origin of higher-order repeat structure in alpha-satellite DNA of
      primate centromeres.
AB  - Alpha-satellite DNA (AS) is a main DNA component of primate centromeres,
      consisting of tandemly repeated units of ~170 bp. The AS of humans contains
      sequences organized into higher-order repeat (HOR) structures, in which a block
      of multiple repeat units forms a larger repeat unit and the larger units are
      repeated tandemly. The presence of HOR in AS is widely thought to be unique to
      hominids (family Hominidae; humans and great apes). Recently, we have identified
      an HOR-containing AS in the siamang, which is a small ape species belonging to
      the genus Symphalangus in the family Hylobatidae. This result supports the view
      that HOR in AS is an attribute of hominoids (superfamily Hominoidea) rather than
      hominids. A single example is, however, not sufficient for discussion of the
      evolutionary origin of HOR-containing AS. In the present study, we developed an
      efficient method for detecting signs of large-scale HOR and demonstrated HOR of
      AS in all the three other genera. Thus, AS organized into HOR occurs widely in
      hominoids. Our results indicate that (i) HOR-containing AS was present in the
      last common ancestor of hominoids or (ii) HOR-containing AS emerged independently
      in most or all basal branches of hominoids. We have also confirmed HOR occurrence
      in centromeric AS in the Hylobatidae family, which remained unclear in our
      previous study because of the existence of AS in subtelomeric regions, in
      addition to centromeres, of siamang chromosomes.

PMID- 24585004
TI  - Resistance to first line platinum paclitaxel chemotherapy in serous epithelial
      ovarian cancer: the prediction value of ERCC1 and Tau expression.
AB  - In oncology, a rational approach to identify patients who are likely to benefit
      from therapy, already before initiation of treatment, is urgently required.
      Excision repair cross-complementation group 1 enzyme (ERCC1) has been proposed as
      a molecular predictor of clinical resistance to platinum-based chemotherapy.
      Other data suggest Tau protein expression as a predictor of clinical outcome in
      cancer patients treated with paclitaxel-based chemotherapy as low tau expression
      may render microtubules more vulnerable to paclitaxel. Therefore, the combination
      of ERCC1 and Tau may be a valuable predictor of sensitivity to
      platinum/paclitaxel treatment. The primary aim of the study was to investigate
      whether ERCC1 and Tau protein expression correlates with patient outcome in newly
      diagnosed epithelial ovarian cancer (EOC) patients. Formalin-fixed, paraffin
      embedded tissue sections from 227 newly diagnosed EOC patients were used for
      immunohistochemical staining for ERCC1 and Tau proteins. All patients received
      standard first-line combination platinum and paclitaxel chemotherapy. The
      patients were divided in a training set of 84 patients and an independent
      validation cohort of 143 patients. Neither ERCC1 nor Tau expression was
      associated with clinical response or platinum resistance in both the training and
      validation sets. Patients with ERCC1-positive tumors had significantly shortened
      progression-free and overall survival compared to patients with ERCC1-negative
      tumors, p<0.00001 and p=0.0006. In multivariate analysis ERCC1 also proved as an
      independent predictor of PFS and OS with HR of 3.86 and 1.98, respectively but
      the data could not be confirmed in the validation set. Tau expression was not
      associated with PFS or OS in this study. ERCC1 and Tau might serve as biomarkers
      of DNA repair and for paclitaxel sensitivity but the present study could not
      validate ERCC1 or Tau protein expression in tumors as pre-treatment tools to
      predict sensitivity to first-line platinum/paclitaxel chemotherapy.

PMID- 24585005
TI  - The provision of potable water in eradication of Guinea worm infection in Ezza
      North, Southeastern, Nigeria.
AB  - Guinea worm is a parasite found in unprotected drinking water sources, causes
      considerable morbidity and loss of agricultural production among rural people.
      The study was to determine the current status of Guinea worm infection in Ezza
      North and to evaluate the impact of control measures on guinea worm infection. A
      total of 200 individuals in Ezza North Southeastern, Nigeria were examined for
      guinea worm infection. A standardized questionnaire was used to determine the
      effect of potable water on guinea worm eradication/control, the source of
      drinking water, information on the knowledge, attitude, symptom management
      practices, availability of health facilities and boreholes installation status.
      The instrument for data collection was well constructed, validated and reliable
      tested questionnaire by an expert. Data obtained was analyzed using Epi-Info
      model 3.4 versions. Results of a study indicated majority of the respondents 195
      (97.5 %) have access to safe drinking water supply which indicated no case of
      Guinea worm infection. The active use of potable water supply was found among the
      age group of 20-30 years 71 (35.5 %) and higher in male (57.5 %) than females
      (42.5 %). The drastic reduction of Guinea worm infection to zero (0) level in
      Ezza North were due to multiple factors as health education, availability of
      functional boreholes, presence of health centers for immediate treatment if any
      case discovered.

PMID- 24585003
TI  - Genome-wide identification, phylogeny, duplication, and expression analyses of
      two-component system genes in Chinese cabbage (Brassica rapa ssp. pekinensis).
AB  - In plants, a two component system (TCS) composed of sensor histidine kinases
      (HKs), histidine phosphotransfer proteins (HPs), and response regulators (RRs)
      has been employed in cytokinin signal transduction. A TCS exhibits important
      functions in diverse biological processes, including plant growth, development,
      and response to environmental stimuli. Conducting an exhaustive search of the
      Chinese cabbage genome, a total of 20 HK(L) (11 HKs and 9 HKLs), 8 HP (7
      authentic and 1 pseudo), and 57 RR (21 Type-A, 17 Type-B, 4 Type-C, and 15
      pseudo) proteins were identified. The structures, conserved domains, and
      phylogenetic relationships of these protein-coding genes were analysed in detail.
      The duplications, evolutionary patterns, and divergence of the TCS genes were
      investigated. The transcription levels of TCS genes in various tissues, organs,
      and developmental stages were further analysed to obtain information of the
      functions of these genes. Cytokinin-related binding elements were found in the
      putative promoter regions of Type-A BrRR genes. Furthermore, gene expression
      patterns to adverse environmental stresses (drought and high salinity) and
      exogenous phytohormones (tZ and ABA) were investigated. Numerous stress
      responsive candidate genes were obtained. Our systematic analyses provided
      insights into the characterization of the TCS genes in Chinese cabbage and basis
      for further functional studies of such genes. 

PMID- 24585006
TI  - Horses and cows might teach us about human knees.
AB  - Our comparative study of the knees of horses and cows (paraphrased as highly
      evolved joggers and as domesticated couch-potatoes, respectively) demonstrates
      significant differences in the posterior sections of bovine and equine tibial
      cartilage, which are consistent with specialisation for gait. These insights were
      possible using a novel analytical measuring technique based on the shearing of
      small biopsy samples, called dynamic shear analysis. We assert that this
      technique could provide a powerful new tool to precisely quantify the pathology
      of osteoarthritis for the medical field. 

PMID- 24585007
TI  - Blood pressure lowering efficacy of nonselective beta-blockers for primary
      hypertension.
AB  - BACKGROUND: Beta-blockers are one of the classes of drugs frequently used to
      treat hypertension. Quantifying the blood pressure (BP) lowering effects of
      nonselective beta-blockers provides important information that aids clinical
      decision making. OBJECTIVES: To quantify the dose-related effects of nonselective
      beta-adrenergic receptor blockers (beta-blockers) on systolic blood pressure
      (SBP) and diastolic blood pressure (DBP) as compared with placebo in people with
      primary hypertension. SEARCH METHODS: We searched the Cochrane Central Register
      of Controlled Trials (CENTRAL), MEDLINE, EMBASE and ClinicalTrials.gov for
      randomized controlled trials up to October 2013. SELECTION CRITERIA: Randomized,
      double-blind, placebo-controlled, parallel or cross-over trials. Studies had to
      contain a nonselective beta-blocker monotherapy arm with a fixed dose.
      Participants enrolled into the studies had to have primary hypertension at
      baseline. Duration of studies had to be between three and 12 weeks. DATA
      COLLECTION AND ANALYSIS: Two review authors (GW and AL) independently confirmed
      the inclusion of studies and extracted the data. MAIN RESULTS: We included 25
      RCTs that evaluated the BP lowering effects of seven nonselective beta-blockers
      in 1264 people with hypertension. Among the 25 RCTs, four were parallel studies
      and 21 were cross-over studies. Overall, nonselective beta-blockers lowered
      systolic BP and diastolic BP compared with placebo. Nonselective beta-blockers,
      in the recommended dose range, did not showed a convincing dose-response
      relationship by direct comparison. The once (1x) and twice (2x) starting dose
      subgroups contained the largest sample size. The estimate of BP lowering efficacy
      for nonselective beta-blockers by combining the 1x and 2x starting dose subgroup
      was -10 mmHg (95% CI -11 to -8) for systolic BP and -7 mmHg (95% CI -8 to -6) for
      diastolic BP (low-quality evidence). Nonselective beta-blockers starting at the
      1x recommended starting doses lowered heart rate by 12 beats per minute (95% CI
      10 to 13) (low-quality evidence). The dose-response relationship in heart rate
      was evident by both direct and indirect comparison. Due to imprecision, there was
      no clear evidence of an effect of nonselective beta-blockers on pulse pressure in
      any dose subgroups except for a small reduction with the 2x starting dose (-2.2
      mmHg, 95% CI -3.7 to -0.7) (very low quality evidence). The point estimates in
      the 1x, four times (4x) and eight times (8x) starting dose subgroups were similar
      to the 2x starting dose subgroup. Therefore, it would appear that if nonselective
      beta-blockers do lower pulse pressure, the magnitude is likely to be about 2
      mmHg. There were very limited data (two studies) on withdrawals due to adverse
      effects (risk ratio (RR) 0.84; 95% CI 0.38 to 1.82). AUTHORS' CONCLUSIONS: In
      people with mild-to-moderate hypertension, nonselective beta-blockers lowered
      peak BP by a mean of -10/-7 mmHg (systolic/diastolic) and reduced heart rate by
      12 beats per minute. Propranolol and penbutolol were the two drugs that
      contributed to most of the data for nonselective beta-blockers. This estimate is
      likely exaggerated due to the presence of extreme outliers and other sources of
      bias. If we removed the extreme outliers from the analysis, the estimate for non
      selective beta-blockers was lower (-8/-5 mmHg (systolic/diastolic)). Nonselective
      beta-blockers did not show a convincing graded dose-response in the recommended
      dose range for systolic BP and diastolic BP, while higher dose nonselective beta
      blockers provided greater reduction of heart rate. Using higher dose nonselective
      beta-blockers might cause more side effects, such as bradycardia, without
      producing an additional BP lowering effect. The effect of nonselective beta
      blockers on pulse pressure was likely small, at about 2 mmHg.

PMID- 24585021
TI  - Right aortic arch with aberrant left subclavian artery and coarctation.

PMID- 24585023
TI  - Low-temperature combustion chemistry of novel biofuels: resonance-stabilized QOOH
      in the oxidation of diethyl ketone.
AB  - The Cl initiated oxidation reactions of diethyl ketone (DEK; 3-pentanone;
      (CH3CH2)2C=O), 2,2,4,4-d4-diethyl ketone (d4-DEK; (CH3CD2)2C=O) and 1,1,1,5,5,5
      d6-diethyl ketone (d6-DEK; (CD3CH2)2C=O) are studied at 8 Torr and 550-650 K
      using Cl2 as a source for the pulsed-photolytic generation of Cl. Products are
      monitored as a function of reaction time, mass, and photoionization energy using
      multiplexed photoionization mass spectrometry with tunable synchrotron radiation.
      Adding a large excess of O2 to the reacting flow allows determination of products
      resulting from oxidation of the initial primary (Rp) and secondary (Rs) radicals
      formed via the Cl + DEK reaction. Because of resonance stabilization, the
      secondary DEK radical (3-oxopentan-2-yl) reaction with O2 has a shallow alkyl
      peroxy radical (RsO2) well and no energetically low-lying product channels. This
      leads to preferential back dissociation of RsO2 and a greater likelihood of
      consumption of Rs by competing radical-radical reactions. On the other hand,
      reaction of the primary DEK radical (3-oxopentan-1-yl) with O2 has several
      accessible bimolecular product channels. Vinyl ethyl ketone is observed from HO2
      elimination from the DEK alkylperoxy radicals, and small-molecule products are
      identified from beta-scission reactions and decomposition reactions of oxy
      radical secondary products. Although channels yielding OH + 3-, 4-, 5- and 6
      membered ring cyclic ether products are possible in the oxidation of DEK, at the
      conditions of this study (8 Torr, 550-650 K) only the 5-membered ring, 2
      methyltetrahydrofuran-3-one, is observed in significant quantities. Computation
      of relevant stationary points on the potential energy surfaces for the reactions
      of Rp and Rs with O2 indicates this cyclic ether is formed via a resonance
      stabilized hydroperoxyalkyl radical (QOOH) intermediate, formed from
      isomerization of the RpO2 radical.

PMID- 24585022
TI  - The neuroinvasive profiles of H129 (herpes simplex virus type 1) recombinants
      with putative anterograde-only transneuronal spread properties.
AB  - The use of viruses as transneuronal tracers has become an increasingly powerful
      technique for defining the synaptic organization of neural networks. Although a
      number of recombinant alpha herpesviruses are known to spread selectively in the
      retrograde direction through neural circuits only one strain, the H129 strain of
      herpes simplex virus type 1, is reported to selectively spread in the anterograde
      direction. However, it is unclear from the literature whether there is an
      absolute block or an attenuation of retrograde spread of H129. Here, we
      demonstrate efficient anterograde spread, and temporally delayed retrograde
      spread, of H129 and three novel recombinants. In vitro studies revealed no
      differences in anterograde and retrograde spread of parental H129 and its
      recombinants through superior cervical ganglion neurons. In vivo injections of
      rat striatum revealed a clear bias of anterograde spread, although evidence of
      deficient retrograde transport was also present. Evidence of temporally delayed
      retrograde transneuronal spread of H129 in the retina was observed following
      injection of the lateral geniculate nucleus. The data also demonstrated that
      three novel recombinants efficiently express unique fluorescent reporters and
      have the capacity to infect the same neurons in dual infection paradigms. From
      these experiments we conclude that H129 and its recombinants not only efficiently
      infect neurons through anterograde transneuronal passage, but also are capable of
      temporally delayed retrograde transneuronal spread. In addition, the capacity to
      produce dual infection of projection targets following anterograde transneuronal
      passage provides an important addition to viral transneuronal tracing technology.

PMID- 24585024
TI  - In vitro and in vivo analyses of the role of the carboxysomal beta-type carbonic
      anhydrase of the cyanobacterium Synechococcus elongatus in carboxylation of
      ribulose-1,5-bisphosphate.
AB  - The carboxylase activities of crude carboxysome preparations obtained from the
      wild-type Synechococcus elongatus strain PCC 7942 strain and the mutant defective
      in the carboxysomal carbonic anhydrase (CA) were compared. The carboxylation
      reaction required high concentrations of bicarbonate and was not even saturated
      at 50 mM bicarbonate. With the initial concentrations of 50 mM and 25 mM for
      bicarbonate and ribulose-1,5-bisphosphate (RuBP), respectively, the initial rate
      of RuBP carboxylation by the mutant carboxysome (0.22 MUmol mg(-1) protein min(
      1)) was only 30 % of that observed for the wild-type carboxysomes (0.71 MUmol mg(
      1) protein min(-1)), indicating the importance of the presence of CA in efficient
      catalysis by ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco). While the
      mutant defective in the ccmLMNO genes, which lacks the carboxysome structure,
      could grow under aeration with 2 % (v/v) CO2 in air, the mutant defective in ccaA
      as well as ccmLMNO required 5 % (v/v) CO2 for growth, indicating that the
      cytoplasmically localized CcaA helped utilization of CO2 by the cytoplasmically
      localized Rubisco by counteracting the action of the CO2 hydration mechanism. The
      results predict that overexpression of Rubisco would hardly enhance CO2 fixation
      by the cyanobacterium at CO2 levels lower than 5 %, unless Rubisco is properly
      organized into carboxysomes. 

PMID- 24585025
TI  - Seasonal, diurnal and vertical variation in photosynthetic parameters in
      Phyllostachys humilis bamboo plants.
AB  - In recent years, temperate bamboo species have been introduced in Europe for
      multiple uses such as renewable bio-based materials (wood, composites, fibres,
      biochemicals...) and numerous ecological functions (soil and water conservation,
      erosion control, phytoremediation...). Despite their interesting potential,
      little is known on the ecophysiology of these plants in their new habitat.
      Therefore, we studied gas exchange parameters on a full soil bamboo plantation of
      Phyllostachys humilis on a test field in Ireland (Europe). We evaluated the
      seasonal, diurnal and vertical variation of the parameters of two commonly used
      photosynthetic models, i.e. the light response curve (LRC) model and the model of
      Farquhar, von Caemmerer and Berry (FvCB). Furthermore, we tested if there were
      environmental effects on the photosynthetic parameters of these models and if a
      correlation between photosynthetic parameters and fluorescence parameters was
      present, fluorescence parameters can be easily and fast determined. Our results
      show that the gas exchange parameters do not vary diurnally or vertically. Only
      seasonal variations were found and should, therefore, be taken into account when
      using the LRC or FvCB model when modelling canopy growth. Therefore, a big-leaf
      model or a sunlit-shade model can be used for modelling bamboo growth in Western
      Europe. There is no straightforward relation between environmental variables and
      the photosynthetic parameters. Although fluorescence parameters showed a
      correlation with the photosynthetic parameters, application of such correlation
      may be limited. 

PMID- 24585039
TI  - Health care expenditures and longevity: is there a Eubie Blake effect?
AB  - It is still an open question whether increasing life expectancy as such causes
      higher health care expenditures (HCE) in a population. According to the "red
      herring" hypothesis, the positive correlation between age and HCE is exclusively
      due to the fact that mortality rises with age and a large share of HCE is caused
      by proximity to death. As a consequence, rising longevity-through falling
      mortality rates-may even reduce HCE. However, a weakness of many previous
      empirical studies is that they use cross-sectional evidence to make inferences on
      a development over time. In this paper, we analyse the impact of rising longevity
      on the trend of HCE over time by using data from a pseudo-panel of German
      sickness fund members over the period 1997-2009. Using (dynamic) panel data
      models, we find that age, mortality and 5-year survival rates each have a
      positive impact on per-capita HCE. Our explanation for the last finding is that
      physicians treat patients more aggressively if the results of these treatments
      pay off over a longer time span, which we call "Eubie Blake effect". A simulation
      on the basis of an official population forecast for Germany is used to isolate
      the effect of demographic ageing on real per-capita HCE over the coming decades.
      We find that, while falling mortality rates as such lower HCE, this effect is
      more than compensated by an increase in remaining life expectancy so that the net
      effect of ageing on HCE over time is clearly positive. 

PMID- 24585040
TI  - Birth cohort and the specialization gap between same-sex and different-sex
      couples.
AB  - We examine differences in household specialization between same-sex and different
      sex couples within and across three birth cohorts: Baby Boomers, Generation X,
      and Generation Y. Using three measures of household specialization, we find that
      same-sex couples are less likely than their different-sex counterparts to exhibit
      a high degree of specialization. However, the "specialization gap" between same
      sex and different-sex couples narrows across birth cohorts. These findings are
      indicative of a cohort effect. Our results are largely robust to the inclusion of
      a control for the presence of children and for subsets of couples with and
      without children. We provide three potential explanations for why the
      specialization gap narrows across cohorts. First, different-sex couples from more
      recent birth cohorts may have become more like same-sex couples in terms of
      household specialization. Second, social and legal changes may have prompted a
      greater degree of specialization within same-sex couples relative to different
      sex couples. Last, the advent of reproductive technologies, which made having
      children easier for same-sex couples from more recent birth cohorts, could result
      in more specialization in such couples relative to different-sex couples. 

PMID- 24585041
TI  - Generic detection and identification of pospiviroids.
AB  - A multiplex one-step RT-PCR aiming at detecting all pospiviroids known to be
      harmful to cultivated plants has been developed. Specificity, sensitivity,
      selectivity, repeatability and reproducibility of this test have been assessed in
      order to fulfill the recommendations of the EPPO standard PM7/98 and provide
      routine detection laboratories with a cost-effective, easy-to-use and robust
      pospiviroid detection test. To further understand the epidemiology and ease the
      management of pospiviroid outbreaks, this RT-PCR diagnostic test can be followed
      by direct sequencing of the amplicons to identify and characterize the detected
      pospiviroid isolates. 

PMID- 24585042
TI  - Comparative analysis of differential gene expression in kidney tissues of
      moribund and surviving crucian carp (Carassius auratus gibelio) in response to
      cyprinid herpesvirus 2 infection.
AB  - Cyprinid herpesvirus 2 (CyHV-2) has recently been associated with high mortality
      of cultured crucian carp (Carassius auratus gibelio) in eastern China. In this
      study, we established a real-time PCR method to confirm viral infection of
      crucian carp and to quantify CyHV-2 particles obtained by sucrose gradient
      centrifugation from diseased fish. Virus-free crucian carp were artificially
      infected with CyHV-2 using an injection method, which resulted in a dose
      dependent death rate. In situ hybridization analysis indicated that there was
      extensive viral replication and lysis in the kidneys of moribund fish, in
      contrast to very limited replication in surviving fish. To probe the host immune
      response to viral infection at the level of gene expression, we identified virus
      responsive genes using suppression subtractive hybridization (SSH) in head kidney
      tissues, the principal immune organ of fish, from moribund and surviving crucian
      carps after viral challenge. From the moribund SSH library, 363 expressed
      sequence tags (ESTs) were clustered to 234 unigenes (including 15 singletons and
      45 contigs). From the survivor SSH library, 599 ESTs was clustered to 549
      unigenes (including 107 singletons and 105 contigs). We further analyzed the
      transcriptional levels of all immune-related genes by quantitative real-time RT
      PCR, which confirmed the upregulation of 90.48 % of these genes. The
      significantly upregulated immune-related genes identified in this study can serve
      as candidate marker genes for acute CyHV-2 infection.

PMID- 24585043
TI  - Association of single-nucleotide polymorphisms in a metabotropic glutamate
      receptor GRM3 gene subunit to alcohol-dependent male subjects.
AB  - AIMS: The purpose of this study was to investigate the association between the
      metabotropic glutamate receptor 3 (GRM3) subunit gene and alcohol dependence by
      the single-nucleotide polymorphisms (SNPs). METHODS: Two hundred and forty-eight
      male alcohol-dependent patients and 235 male control subjects were recruited. Ten
      SNPs in the GRM3 region were studied, and genotyping of SNPs was performed by
      ligase detection reactions. RESULTS: We found highly significant differences in
      allele and genotype frequencies of rs6465084 between the alcohol-dependent and
      control group, with the greater frequency of A allele of SNP rs6465084 in alcohol
      dependent group. We also found significant differences of haplotype frequencies
      in five combinations (including TAATATT, CAGTATT, TCGTATT, CAATAGC, TAATATC) in
      the linkage disequilibrium constructed by seven SNPs between the groups.
      CONCLUSION: Our results supplied the first evidence that the polymorphism of GRM3
      gene associates with the morbidity of alcohol dependence in human being, which
      may support a new potential target for alcoholism treatment.

PMID- 24585044
TI  - Assessment of small C-fiber status for screening of oxidative stress in patients
      at risk of diabetes.
AB  - Oxidized LDL (oxLDL), anti-oxLDL antibody (anti-oxLDL) and paraoxonase (PON1) are
      increasingly being reported to be associated with diabetic atherosclerosis.
      Oxidative stress could affect also small C-fibers innervating the sweat glands
      even in prediabetes. Hence it could be hypothesized that sweat dysfunction may be
      a predictor of oxidative stress status for early detection of diabetes. Ezscan, a
      new device, has recently been developed to measure the sweat function. Therefore,
      this study was aimed to determine the relevance of this Ezscan method to identify
      impairment in oxidative stress parameters. Plasma levels of oxLDL and anti-oxLDL
      were measured by enzyme immunoassay and ELISA respectively. Small C-fiber status
      was assessed by measurement of hand and foot sweat function with the help of
      Ezscan device and subsequent calculation of a risk score. Out of 82 subjects
      recruited in this study, 38 had impaired glucose tolerance and 6 had newly
      diagnosed diabetes mellitus. Ezscan risk score was significantly (p=0.004)
      correlated with oxLDL/anti-oxLDL ratio (0.32). Area under the curve (AUC) of
      receiver operating characteristics (ROC) analysis for detection of oxLDL/anti
      oxLDL ratio (>0.12) was 0.76. For an Ezscan risk score of 50%, the sensitivity
      and specificity were 68% and 71% respectively. After adjustment for age and BMI,
      PON1 activity showed significant difference among the 3 risk groups defined by
      Ezscan risk score. Based on these results it may be concluded that Ezscan could
      be a useful screening tool in daily practice to assess alterations in oxidative
      stress parameters in individuals at risk of developing diabetes. 

PMID- 24585045
TI  - A phase I study of irinotecan and pegylated liposomal doxorubicin in recurrent
      ovarian cancer (Tohoku Gynecologic Cancer Unit 104 study).
AB  - PURPOSE: A phase I clinical study was conducted to determine the maximum
      tolerated dose (MTD) and the recommended dose (RD) of irinotecan hydrochloride
      (CPT-11) in CPT-11/pegylated liposomal doxorubicin (PLD) combination therapy, a
      novel treatment regimen for platinum- and taxane-resistant recurrent ovarian
      cancer. METHODS: Pegylated liposomal doxorubicin was administered intravenously
      on day 3 at a fixed dose of 30 mg/m(2). CPT-11 was administered intravenously on
      days 1 and 15, at a dose of 50 mg/m(2) on both days. One course of chemotherapy
      was 28 days, and patients were given a maximum of six courses, with the CPT-11
      dose being increased in increments of 10 mg/m(2) (level 1, 50 mg/m(2); level 2,
      60 mg/m(2); level 3, 70 mg/m(2); level 4, 80 mg/m(2)) to determine MTD and RD.
      RESULTS: During the period from April 2010 to March 2013, three patients were
      enrolled for each level. In the first course, no dose-limiting toxicity occurred
      in any of the patients. Grade 4 neutropenia was observed in two of three patients
      at level 4. At level 4, the antitumor effect was a partial response (PR) in two
      of the three patients and stable disease (SD) in one. At level 3, one of the
      three patients showed PR and two had SD. At level 4, the start of the next course
      was postponed in two of three patients. In addition, one patient at level 4
      experienced hemotoxicity that met the criteria for dose reduction in the next
      course. The above results suggested that administration of CPT-11 at dose level 5
      (90 mg/m(2)) would result in more patients with severe neutropenia and in more
      patients requiring postponement of the next course or a dose reduction. Based on
      the above, the RD of CPT-11 was determined to be 80 mg/m(2). CONCLUSIONS: The
      results suggest that CPT-11/PLD combination therapy for recurrent ovarian cancer
      is a useful treatment method with a high response rate and manageable adverse
      reactions. In the future phase II study, the safety and efficacy of this therapy
      will be assessed at 80 mg/m(2) of CPT-11 and 30 mg/m(2) of PLD.

PMID- 24585046
TI  - Intravesical mitomycin C combined with local microwave hyperthermia in non-muscle
      invasive bladder cancer with increased European Organization for Research and
      Treatment of Cancer (EORTC) score risk of recurrence and progression.
AB  - PURPOSE: To assess the activity of intravesical chemotherapy and local microwave
      hyperthermia (ICLMH) in increasing the disease-free interval (DFI) in patients
      with non-muscle-invasive bladder cancer (NMIBC) and treatment toxicity. METHODS:
      Forty-two patients with a diagnosis of high-risk NMIBC, according to the European
      Organization for Research and Treatment of Cancer (EORTC) criteria, were treated
      with an intensive schedule of ICLMH using 40 mg mitomycin C. The treatment
      consisted of 4 weekly sessions, followed by 6 sessions delivered every 2 weeks,
      and by 4 monthly sessions, for a total of 14 sessions over 8 months. The DFIs
      before and after treatment were compared in each patient. RESULTS: The schedule
      was completed as planned by 32 patients (76.2 %). The percentage of disease-free
      patients the year before study was 14.9 % (95 % CI 5.5-28.8) versus 88.8 % (95 %
      CI 73.7-94.8) after ICLMH (p < 0.0001). Patient EORTC scores, multifocality, and
      tumour stage were all associated significantly and independently with a higher
      risk of recurrence after ICLMH treatment with HR of 41.1 (p = 0.01), 17.7 (p =
      0.02), and 8.5 (p = 0.02), respectively. After a median follow-up of 38 months,
      24 patients (57.1 %) did not show evidence of disease, whereas 13 patients (30.9
      %) underwent disease recurrence and 5 patients (11.9 %) showed also stage
      progression. Toxicity consisted in grades 1 and 2 frequency, non-infectious
      cystitis, and haematuria. CONCLUSIONS: ICLMH significantly increases the DFI of
      NMIBC patients with high EORTC score for recurrence and progression. Toxicity of
      the intensive treatment schedule was generally mild.

PMID- 24585047
TI  - Tibial eminence fractures in the paediatric population: a systematic review.
AB  - INTRODUCTION: We present a systematic review of the literature for the management
      of tibial eminence fractures in the paediatric population. Our aims were to
      assess modalities of injury, treatment options available and their associated
      complications. MATERIALS AND METHODS: We found 740 relevant citations in the
      English literature up to 1 October 2012, of which 36 full text articles met our
      inclusion criteria. RESULTS: Our results show that skiing, sports and motor
      vehicle accidents are increasingly common modes of injury, in addition to the
      commonly described fall off of a bicycle. Most studies advocate non-operative
      management for type I Meyer's and McKeever's fractures and reduction and internal
      fixation for type II and III fractures. Better long-term results have been
      reported with arthroscopic surgery compared to open surgery. There is no
      consensus as to which type of fixation is best suited for tibial eminence
      fractures; methods available include excision of the bony fragment, K-wire, screw
      and, absorbable suture fixation, and more recently, suture anchor and meniscal
      arrow. The main complications reported include arthrofibrosis, non-union, mal
      union, pain and severe laxity. Early post-operative range of motion exercises
      have been shown to reduce the incidence of arthrofibrosis. CONCLUSION: As all
      papers report results from small case series, Level I studies are required to
      produce more definitive evidence for the management of paediatric tibial eminence
      fractures.

PMID- 24585048
TI  - [Therapy monitoring of neoadjuvant therapy with MRI. RECIST and functional
      imaging].
AB  - CLINICAL/METHODICAL ISSUE: Neoadjuvant chemotherapy is increasingly being applied
      in patients with operable breast cancer. Thus, an early prediction of response to
      neoadjuvant chemotherapy is of high relevance. STANDARD RADIOLOGICAL METHODS: The
      interobserver variability of clinical examination, mammography and
      ultrasonography in the assessment of response to neoadjuvant chemotherapy is
      high. METHODICAL INNOVATIONS: Magnetic resonance imaging (MRI) allows the
      assessment of functional parameters in addition to changes in tumor size and
      morphology. PERFORMANCE: A reliable therapy response monitoring aims at
      optimizing individualized patient care. ACHIEVEMENTS: This paper summarizes
      current guidelines for the assessment of response to neoadjuvant chemotherapy in
      breast cancer according to the response evaluation criteria in solid tumors
      (RECIST). Furthermore, the technical principles of MRI-based therapy monitoring
      are described and an overview of the clinical studies that have assessed the
      feasibility of functional MRI in response to treatment evaluation is given.
      PRACTICAL RECOMMENDATIONS: The technology of functional MRI offers promising
      results concerning therapy response monitoring. However, the level of evidence is
      not sufficiently evaluated for the technologies of functional MRI presented here.

PMID- 24585049
TI  - Molecular microbiology in antibacterial research.
AB  - The special issue of Journal of Microbiology contains six reviews dealing with
      cutting edge research achievements in the fields of molecular microbiology
      focusing on antibacterial research. In a more specific sense, this special issue
      helps outline the progress of 21(st)-century basic molecular microbiology that
      can encompass related disciplines regarding a variety of interactions involving
      bacteria during bacterial pathogenesis and their control: sociomicrobiology
      (interaction between bacteria), immunology (interaction between bacteria and
      their hosts), and bacteriophage (phage) virology (interaction between bacteria
      and their parasites). Recent advancements have rapidly been made in our
      understanding of the real situation regarding polymicrobial interactions during
      bacterial infection and in non-mammalian host infection models to uncover the
      molecular mechanisms of host-bacteria interactions, which will complement our
      growing knowledge about immune responses toward bacterial and environmental
      elicitors. Moreover, much attention has recently been paid to phages and phage
      products as potential antibacterial therapeutics in the era of antibiotic
      resistance. Below, I summarize the individual contributions in these distinct
      categories. 

PMID- 24585050
TI  - Mechanisms of synergy in polymicrobial infections.
AB  - Communities of microbes can live almost anywhere and contain many different
      species. Interactions between members of these communities often determine the
      state of the habitat in which they live. When these habitats include sites on the
      human body, these interactions can affect health and disease. Polymicrobial
      synergy can occur during infection, in which the combined effect of two or more
      microbes on disease is worse than seen with any of the individuals alone.
      Powerful genomic methods are increasingly used to study microbial communities,
      including metagenomics to reveal the members and genetic content of a community
      and metatranscriptomics to describe the activities of community members. Recent
      efforts focused toward a mechanistic understanding of these interactions have led
      to a better appreciation of the precise bases of polymicrobial synergy in
      communities containing bacteria, eukaryotic microbes, and/or viruses. These
      studies have benefited from advances in the development of in vivo models of
      polymicrobial infection and modern techniques to profile the spatial and chemical
      bases of intermicrobial communication. This review describes the breadth of
      mechanisms microbes use to interact in ways that impact pathogenesis and
      techniques to study polymicrobial communities. 

PMID- 24585051
TI  - Enterococcus infection biology: lessons from invertebrate host models.
AB  - The enterococci are commensals of the gastrointestinal tract of many metazoans,
      from insects to humans. While they normally do not cause disease in the
      intestine, they can become pathogenic when they infect sites outside of the gut.
      Recently, the enterococci have become important nosocomial pathogens, with the
      majority of human enterococcal infections caused by two species, Enterococcus
      faecalis and Enterococcus faecium. Studies using invertebrate infection models
      have revealed insights into the biology of enterococcal infections, as well as
      general principles underlying host innate immune defense. This review highlights
      recent findings on Enterococcus infection biology from two invertebrate infection
      models, the greater wax moth Galleria mellonella and the free-living
      bacteriovorous nematode Caenorhabditis elegans. 

PMID- 24585052
TI  - Chronic obstructive pulmonary disease (COPD): evaluation from clinical,
      immunological and bacterial pathogenesis perspectives.
AB  - Chronic obstructive pulmonary disease (COPD), a disease manifested by
      significantly impaired airflow, afflicts ~14.2 million cases in the United States
      alone with an estimated 63 million people world-wide. Although there are a number
      of causes, the predominant cause is excessive tobacco smoke. In fact, in China,
      there have been estimates of 315,000,000 people that smoke. Other less frequent
      causes are associated with indirect cigarette smoke, air pollutants, biomass
      fuels, and genetic mutations. COPD is often associated with heart disease, lung
      cancer, osteoporosis and conditions can worsen in patients with sudden falls.
      COPD also affects both innate and adaptive immune processes. Cigarette smoke
      increases the expression of matrix metalloproteases and proinflammatory
      chemokines and increases lung titers of natural killer cells and neutrophils.
      Yet, neutrophil reactive oxygen species (ROS) mediated by the phagocytic
      respiratory burst and phagocytosis is impaired by nicotine. In contrast to innate
      immunity in COPD, dendritic cells represent leukocytes recruited to the lung that
      link the innate immune responses to adaptive immune responses by activating naive
      T cells through antigen presentation. The autoimmune process that is also a
      significant part of inflammation associated with COPD. Moreover, coupled with
      restricted FEV1 values, are the prevalence of patients with single or multiple
      infections by bacteria, viruses and fungi. Finally, we focus on one of the more
      problematic infectious agents, the Gram-negative opportunistic pathogenic
      bacterium, Pseudomonas aeruginosa. Specifically, we delve into the development of
      highly problematic biofilm infections that are highly refractory to conventional
      antibiotic therapies in COPD. We offer a non-conventional, biocidal treatment
      that may be effective for COPD airway infections as well as with combinations of
      current antibiotic regimens for more effective treatment outcomes and relief for
      patients with COPD. 

PMID- 24585053
TI  - Perturbation of pulmonary immune functions by carbon nanotubes and susceptibility
      to microbial infection.
AB  - Occupational and environmental pulmonary exposure to carbon nanotubes (CNT) is
      considered to be a health risk with a very low threshold of tolerance as
      determined by the United States Center for Disease Control. Immortalized airway
      epithelial cells exposed to CNTs show a diverse range of effects including
      reduced viability, impaired proliferation, and elevated reactive oxygen species
      generation. Additionally, CNTs inhibit internalization of targets in multiple
      macrophage cell lines. Mice and rats exposed to CNTs often develop pulmonary
      granulomas and fibrosis. Furthermore, CNTs have immunomodulatory properties in
      these animal models. CNTs themselves are proinflammatory and can exacerbate the
      allergic response. However, CNTs may also be immunosuppressive, both locally and
      systemically. Studies that examined the relationship of CNT exposure prior to
      pulmonary infection have reached different conclusions. In some cases, pre
      exposure either had no effect or enhanced clearance of infections while other
      studies showed CNTs inhibited clearance. Interestingly, most studies exploring
      this relationship use pathogens which are not considered primary pulmonary
      pathogens. Moreover, harmony across studies is difficult as different types of
      CNTs have dissimilar biological effects. We used Pseudomonas aeruginosa as model
      pathogen to study how helical multi-walled carbon nanotubes (HCNTs) affected
      internalization and clearance of the pulmonary pathogen. The results showed that,
      although HCNTs can inhibit internalization through multiple processes, bacterial
      clearance was not altered, which was attributed to an enhanced inflammatory
      response caused by pre-exposure to HCNTs. We compare and contrast our findings in
      relation to other studies to gauge the modulation of pulmonary immune response by
      CNTs. 

PMID- 24585054
TI  - When a virus is not a parasite: the beneficial effects of prophages on bacterial
      fitness.
AB  - Most organisms on the planet have viruses that infect them. Viral infection may
      lead to cell death, or to a symbiotic relationship where the genomes of both
      virus and host replicate together. In the symbiotic state, both virus and cell
      potentially experience increased fitness as a result of the other. The viruses
      that infect bacteria, called bacteriophages (or phages), well exemplify the
      symbiotic relationships that can develop between viruses and their host. In this
      review, we will discuss the many ways that prophages, which are phage genomes
      integrated into the genomes of their hosts, influence bacterial behavior and
      virulence. 

PMID- 24585056
TI  - Treatment of obsessive-compulsive disorder in a nationwide survey of office-based
      physician practice.
AB  - OBJECTIVE: This study examined treatment of obsessive-compulsive disorder (OCD)
      in office-based practice. METHODS: Data from the 2003- 2010 National Ambulatory
      Medical Care Survey, a nationally representative survey of visits to U.S. office
      based physicians, were used to examine outpatient visits involving treatment of
      adults with OCD. RESULTS: Among the 316 visits with a diagnosis of OCD, most were
      to a physician seen previously by the patient (96%), usually a psychiatrist
      (86%), and most patients (56%) had seen the physician at least six times in the
      previous year. Most visits included psychotropic medications (84%), most commonly
      a serotonin reuptake inhibitor (SRI) (69%). Visits less commonly included
      psychotherapy (39%). CONCLUSIONS: OCD was predominantly treated by psychiatrists
      using SRIs, despite the prevalence of OCD in primary care and SRI prescribing
      practices in that setting. Given the potential shift in OCD treatment patterns
      after health care reform, research on OCD treatment in primary care is warranted.

PMID- 24585055
TI  - Phage lysis: three steps, three choices, one outcome.
AB  - The lysis of bacterial hosts by double-strand DNA bacteriophages, once thought to
      reflect merely the accumulation of sufficient lysozyme activity during the
      infection cycle, has been revealed to recently been revealed to be a carefully
      regulated and temporally scheduled process. For phages of Gramnegative hosts,
      there are three steps, corresponding to subversion of each of the three layers of
      the cell envelope: inner membrane, peptidoglycan, and outer membrane. The pathway
      is controlled at the level of the cytoplasmic membrane. In canonical lysis, a
      phage encoded protein, the holin, accumulates harmlessly in the cytoplasmic
      membrane until triggering at an allele-specific time to form micron-scale holes.
      This allows the soluble endolysin to escape from the cytoplasm to degrade the
      peptidoglycan. Recently a parallel pathway has been elucidated in which a
      different type of holin, the pinholin, which, instead of triggering to form large
      holes, triggers to form small, heptameric channels that serve to depolarize the
      membrane. Pinholins are associated with SAR endolysins, which accumulate in the
      periplasm as inactive, membrane-tethered enzymes. Pinholin triggering collapses
      the proton motive force, allowing the SAR endolysins to refold to an active form
      and attack the peptidoglycan. Surprisingly, a third step, the disruption of the
      outer membrane is also required. This is usually achieved by a spanin complex,
      consisting of a small outer membrane lipoprotein and an integral cytoplasmic
      membrane protein, designated as o-spanin and i-spanin, respectively. Without
      spanin function, lysis is blocked and progeny virions are trapped in dead
      spherical cells, suggesting that the outer membrane has considerable tensile
      strength. In addition to two-component spanins, there are some single-component
      spanins, or u-spanins, that have an N-terminal outer-membrane lipoprotein signal
      and a C-terminal transmembrane domain. A possible mechanism for spanin function
      to disrupt the outer membrane is to catalyze fusion of the inner and outer
      membranes. 

PMID- 24585057
TI  - Outer membrane protein F stabilised with minimal amphipol forms linear arrays and
      LPS-dependent 2D crystals.
AB  - Amphipols (APol) are polymers which can solubilise and stabilise membrane
      proteins (MP) in aqueous solutions. In contrast to conventional detergents, APol
      are able to keep MP soluble even when the free APol concentration is very low.
      Outer membrane protein F (OmpF) is the most abundant MP commonly found in the
      outer membrane (OM) of Escherichia coli. It plays a vital role in the transport
      of hydrophilic nutrients, as well as antibiotics, across the OM. In the present
      study, APol was used to solubilise OmpF to characterize its interactions with
      molecules such as lipopolysaccharides (LPS) or colicins. OmpF was reconstituted
      into APol by the removal of detergents using Bio-Beads followed by size-exclusion
      chromatography (SEC) to remove excess APol. OmpF/APol complexes were then
      analysed by SEC, dynamic light scattering (DLS) and transmission electron
      microscopy (TEM). TEM showed that in the absence of free APol-OmpF associated as
      long filaments with a thickness of ~6 nm. This indicates that the OmpF trimers
      lie on their sides on the carbon EM grid and that they also favour side by side
      association. The formation of filaments requires APol and occurs very rapidly.
      Addition of LPS to OmpF/APol complexes impeded filament formation and the trimers
      form 2D sheets which mimic the OM. Consequently, free APol is undoubtedly
      required to maintain the homogeneity of OmpF in solutions, but 'minimum APol'
      provides a new phase, which can allow weaker protein-protein and protein-lipid
      interactions characteristic of native membranes to take place and thus control 1D
      2D crystallisation.

PMID- 24585058
TI  - Identification of BMP2 as an epigenetically silenced growth inhibitor in
      rhabdomyosarcoma.
AB  - Rhabdomyosarcoma (RMS) is the most common soft-tissue sarcoma of infancy and
      although therapy has improved over the years, mortality is still fairly high. The
      establishment of new treatments has been hampered by the limited knowledge of the
      molecular mechanisms driving development of RMS. One characteristic of cancer
      cells is aberrant DNA methylation, which could lead to silencing of tumor
      suppressor genes. However, only a few epigenetically silenced genes have been
      described in RMS so far. We performed an expression profiling analysis of three
      RMS cell lines that were treated with the demethylating agent 5'-aza-2'
      deoxycytidine (5-Aza-dC) facilitating re-expression of epigenetically silenced
      genes. This treatment induced the gene BMP2 (bone morphogenetic protein 2)
      throughout all cell lines. Detailed methylation analysis of CpG sites in the BMP2
      promoter region by bisulfite sequencing and methylation-specific PCR revealed
      that a high degree of DNA methylation is causatively associated with the
      suppression of BMP2 in RMS cells. Consequently, treatment of the RMS cell lines
      with 5-Aza-dC resulted in DNA demethylation of the BMP2 promoter, most
      prominently in alveolar RMS. Supplementation of recombinant human BMP2 (rhBMP2)
      led to a reduced viability of RMS cells. Altogether, these findings suggest that
      suppression of BMP2 by epigenetic silencing may play a critical role in the
      genesis of RMS, thereby providing a rationale for the development of a new
      treatment strategy for RMS.

PMID- 24585069
TI  - Granular bodies in root primary meristem cells of Zea mays L. var. Cuscoensis K.
      (Poaceae) that enter young vacuoles by invagination: a novel ribophagy mechanism.
AB  - Because it has a very large, very rapidly growing primary root, we evaluated
      giant maize (Zea mays var. Cuscoensis) as a model organism for root research.
      Granular inclusions are a common feature of cells in many organisms, but they are
      not common in root meristems. We here report the presence of granules in root tip
      cells of giant maize. Seeds were germinated at 20  degrees C in sterile
      conditions. Four to 5-day-old primary roots were fixed, embedded, and sectioned
      for light and electron microscopy. Granules (1-2 MUm) were observed in small
      vacuoles in all cell types of the apical meristem zone and mainly in parenchyma
      cells of the procambium in the primary meristem zone. Some sections were treated
      with ribonuclease and/or proteinase and then stained with toluidine blue, methyl
      green pyronin, or Coomassie brilliant blue. The results were used to determine
      that the granules were composed primarily of RNA and protein. In electron
      micrographs, consistent with the enzyme experiment results, granules appeared to
      be dense aggregates of polyribosomes and rough endoplasmic reticulum. They formed
      first in the cytosol, then invaginated into an adjacent vacuole. The granules are
      apparently ephemeral and therefore may not have a function other than being
      subject to autolysis. We speculate that they are part of a previously undescribed
      ribophagy system that operates during rapid cell growth and differentiation to
      regulate translation and recycle granule components. 

PMID- 24585070
TI  - Fast and reliable class-selective isoflavone index determination on carbon
      nanotube press-transferred electrodes using microfluidic chips.
AB  - Single-walled carbon nanotube press-transferred electrodes (SWPTEs) are new
      disposable electrodes where carbon nanotubes act as exclusive electrochemical
      transducers, being an excellent alternative to common approaches in the field. In
      the current work, these pioneering SWPTEs coupled to microfluidic chips (MCs)
      have been employed to develop their first real application. A class-selective
      electrochemical isoflavone index determination has been proposed for fast and
      reliable qualitative and quantitative assessment of class-isoflavones based on
      the co-migration of the total glycosides (TG) and total aglycones (TA) in less
      than 250 s with very good intra-SWPTE repeatability (RSDs <= 8%, n = 5) and inter
      SWPTE reproducibility (RSDs <= 9%, n = 3). These novel SWPTEs are entering with
      important roles into the micro and nanotechnology scenes expanding new frontiers
      in the food analysis and health field. 

PMID- 24585059
TI  - Potential contribution of dopaminergic gene variants in ADHD core traits and co
      morbidity: a study on eastern Indian probands.
AB  - Association of dopaminergic genes, mainly receptors and transporters, with
      Attention Deficit Hyperactivity Disorder (ADHD) has been investigated throughout
      the world due to the importance of dopamine (DA) in various physiological
      functions including attention, cognition and motor activity, traits. However,
      till date, etiology of ADHD remains unknown. We explored association of
      functional variants in the DA receptor 2 (rs1799732 and rs6278), receptor 4 (exon
      3 VNTR and rs914655), and transporter (rs28363170 and rs3836790) with
      hyperactivity, cognitive deficit, and co-morbid disorders in eastern Indian
      probands. Diagnostic and Statistical Manual for Mental Disorders-IV was followed
      for recruitment of nuclear families with ADHD probands (N = 160) and ethnically
      matched controls (N = 160). Cognitive deficit and hyperactive traits were
      measured using Conner's parents/teachers rating scale. Peripheral blood was
      collected after obtaining informed written consent and used for genomic DNA
      isolation. Genetic polymorphisms were analyzed by PCR-based methods followed by
      population- as well as family-based statistical analyses. Association between
      genotypes and cognitive/hyperactivity traits and co-morbidities was analyzed by
      the Multifactor dimensionality reduction (MDR) software. Case-control analysis
      showed statistically significant difference for rs6278 and rs28363170 (P = 0.004
      and 1.332e-007 respectively) while family-based analysis exhibited preferential
      paternal transmission of rs28363170 '9R' allele (P = 0.04). MDR analyses revealed
      independent effects of rs1799732, rs6278, rs914655, and rs3836790 in ADHD.
      Significant independent effects of different sites on cognitive/hyperactivity
      traits and co-morbid disorders were also noticed. It can be summarized from the
      present investigation that these gene variants may influence
      cognitive/hyperactive traits, thereby affecting the disease etiology and
      associated co-morbid features.

PMID- 24585071
TI  - Questioning the role of axillary node dissection in sentinel node positive early
      stage breast cancer in the South Eastern Cancer Centre.
AB  - INTRODUCTION: Axillary node status is a predictor of breast cancer survival.
      Axillary node dissection (ALND) following positive sentinel node biopsy (SLNB) is
      challenged by the American College of Surgeons Z0011 trial, where
      clinically/radiologically node-negative, SLNB positive early stage patients
      failed to derive therapeutic benefit from ALND at 6 years. AIMS: To quantify the
      rates of non-sentinel lymph node positivity after ALND in all breast cancer
      stages. To assess Z0011 trial result application to an Irish patient population.
      METHODS: Retrospective review of a prospectively maintained database of
      clinically node-negative patients undergoing breast conserving surgery and ALND
      for a positive SLNB from January 2011 to January 2012. RESULTS: Of 174 new breast
      cancers diagnosed, 144 underwent surgery of which 127 patients were
      clinically/radiologically node-negative; 46 patients were SLNB positive; 34 (73.9
      %) proceeded to ALND. Of 9 T1 tumours, 3 (33.3 %) had further positive nodes on
      ALND. Of 24 T2 tumours, 11 (45.8 %) had further positive nodes on ALND. All 3
      (100 %) T3/T4 tumours had further positive nodes on ALND. Mean numbers of
      sentinel and axillary nodes harvested were 2.3 and 15.2, respectively. In the
      SLNB positive, ALND negative group, 12 of 18 (66.7 %) patients were <60 years
      versus 14 of 17 (82.4 %) in the SLNB positive, ALND positive group. This may be
      indicative that younger women have a trend toward node positivity following ALND
      for a positive SLNB. CONCLUSION: These data suggest that a significant proportion
      (41.9 %) of T1/T2 tumours undergoing ALND following positive SLNB have further
      positive nodes. It may be premature to exclude ALND in patients with T1/T2
      tumours following a positive SLNB.

PMID- 24585072
TI  - Reducing sibling conflict in maltreated children placed in foster homes.
AB  - Sibling aggression among maltreated children placed in foster homes is linked to
      other externalizing problems and placement disruption. The reduction of sibling
      conflict and aggression may be achieved via a multicomponent ecologically focused
      intervention for families in the foster care system. The focus of the study is to
      evaluate the feasibility and short-term effectiveness of a transtheoretical
      intervention model targeting sibling pairs and their foster parent that
      integrates family systems, social learning theory, and a conflict mediation
      perspective. In this pilot study, sibling pairs (N = 22) and their foster parent
      were randomized into a three-component intervention (n = 13) or a comparison (n =
      9) group. Promoting Sibling Bonds (PSB) is an 8-week prevention intervention
      targeting maltreated sibling pairs ages 5-11 years placed together in a foster
      home. The siblings, parent, and joint components were delivered in a program
      package at the foster agency by a trained two-clinician team. Average attendance
      across program components was 73 %. Outcomes in four areas were gathered at pre-
      and postintervention: observed sibling interaction quality (positive and
      negative) including conflict during play, and foster parent reports of mediation
      strategies and sibling aggression in the foster home. At postintervention,
      adjusting for baseline scores and child age, intervention pairs showed higher
      positive (p < 0.001) and negative (p < 0.05) interaction quality and lower
      sibling conflict during play (p < 0.01) than comparison pairs. Foster parents in
      the intervention group reported a higher number of conflict mediation strategies
      than those in the comparison group (p < 0.001). Foster parents in the
      intervention group reported lower sibling physical aggression from the older
      toward the younger child than those in the comparison group (p < 0.05). Data
      suggest that the PSB intervention is a promising approach to reduce conflict and
      promote parental mediation, which together may reduce sibling aggression in the
      foster home. 

PMID- 24585073
TI  - DTB Select: 3 | March 2014.
AB  - Every month, DTB scans sources of information on treatments, disease management
      and other healthcare topics for key items to bring to our readers' attention and
      help them keep up to date. To do this, we produce succinct, contextualised
      summaries of the information concerned. We also include comments on, for example,
      the strengths of the information, whether it contains anomalies, ambiguities,
      apparent error or omissions, or whether or how it affects current practice. 

PMID- 24585074
TI  - Literature-based automated reconstruction, expansion, and refinement of the TGF
      beta superfamily ligand-receptor network.
AB  - The TGF-beta pathway transduces a variety of extracellular signals into
      intracellular responses that control multiple cellular processes, including cell
      growth, apoptosis, and differentiation. It encompasses 33 ligands that interact
      with 7 type II receptors and 5 type I receptors at the plasma membrane to
      potentially form 1,155 ligand-receptor complexes in mammalian cells. Retrieving
      the information of the complexes that are actually formed from reading the
      literature might be tedious and prone to missing links. Here, we have developed
      an automated literature-mining procedure to obtain the interactions of the TGF
      beta ligand-receptor network. By querying the Information Hyperlinked over
      Proteins (iHOP) online service and processing the results, we were able to find
      pairwise interactions between ligands and receptors that allowed us to build the
      network automatically from the literature. Comparison with available published
      review papers indicates that this method is able to automatically reconstruct and
      expand the TGF-beta superfamily ligand-receptor network. Retrieving and parsing
      the full text of the manuscripts containing the interactions allowed us to refine
      the network interactions for specific cell lines. 

PMID- 24585075
TI  - Seohaeicola westpacificensis sp. nov., a novel member of genera Seohaeicola
      isolated from deep West Pacific Sea water.
AB  - Strain JL2247(T), an aerobic, Gram-negative, gliding motile bacterium, was
      isolated from the western Pacific at the depth of 2,000 m. The cell was spindle
      shaped with two narrow poles, and flagella were not observed. The colony was
      circular, translucent, and milky. This strain showed catalase-positive and
      oxidase-negative reactions. Its optimal growth conditions were at 32  degrees C,
      pH 7.3, and 3 % NaCl. The predominant polar lipids were phosphatidylcholine,
      diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, and
      phosphatidylmonomethylethanolamine. The major fatty acids were summed feature 8
      (18:1 w7c and/or 18:1 w6c) and Cyclo C19:0 omega8c and the major respiratory
      quinone was Q-10. The DNA G+C content of strain JL2247(T) was 72.6 mol%.
      Phylogenetic analyses based on 16S rRNA gene sequences showed that strain
      JL2247(T) fell into the genus Seohaeicola, family Rhodobacteraceae, order
      Rhodobacterales, class Alphaproteobacteria, sharing the highest similarity with
      the only species Seohaeicola saemankumensis SD-15(T) (96.4 % similarity). From
      the phenotypic, genotypic, and chemotaxonomic data, strain JL2247(T) represents a
      novel species of the genus Seohaeicola and the name is proposed as Seohaeicola
      westpacificensis sp. nov. The type strain is JL2247(T) (=CGMCC 1.12198(T) =
      JCM18883).

PMID- 24585077
TI  - Computational modelling of emboli travel trajectories in cerebral arteries:
      influence of microembolic particle size and density.
AB  - Ischaemic stroke is responsible for up to 80% of stroke cases. Prevention of the
      reoccurrence of ischaemic attack or stroke for patients who survived the first
      symptoms is the major treatment target. Accurate diagnosis of the emboli source
      for a specific infarction lesion is very important for a better treatment for the
      patient. However, due to the complex blood flow patterns in the cerebral arterial
      network, little is known so far of the embolic particle flow trajectory and its
      behaviour in such a complex flow field. The present study aims to study the
      trajectories of embolic particles released from carotid arteries and basilar
      artery in a cerebral arterial network and the influence of particle size, mass
      and release location to the particle distributions, by computational modelling.
      The cerebral arterial network model, which includes major arteries in the circle
      of Willis and several generations of branches from them, was generated from MRI
      images. Particles with diameters of 200, 500 and 800 MUm and densities of 800,
      1,030 and 1,300 kg/m(3) were released in the vessel's central and near-wall
      regions. A fully coupled scheme of particle and blood flow in a computational
      fluid dynamics software ANASYS CFX 13 was used in the simulations. The results
      show that heavy particles (density large than blood or a diameter larger than 500
      MUm) normally have small travel speeds in arteries; larger or lighter embolic
      particles are more likely to travel to large branches in cerebral arteries. In
      certain cases, all large particles go to the middle cerebral arteries; large
      particles with higher travel speeds in large arteries are likely to travel at
      more complex and tortuous trajectories; emboli raised from the basilar artery
      will only exit the model from branches of basilar artery and posterior cerebral
      arteries. A modified Circle of Willis configuration can have significant
      influence on particle distributions. The local branch patterns of internal
      carotid artery to middle cerebral artery and anterior communicating artery can
      have large impact on such distributions.

PMID- 24585076
TI  - A staining method for assessing the viability of Esteya vermicola conidia.
AB  - The viability of conidia of Esteya vermicola, a potentially important biocontrol
      agent against the pinewood nematode Bursaphelenchus xylophilus, is usually
      determined by cultivation for 18-48 h in culture medium. As an alternative to
      this labor-intensive method, we have developed a rapid, simple, and low-cost
      staining method for assessing E vermicola conidia survival rates. A mixture of
      neutral red and methylene blue was found to be the most optimal among several
      stains that also included safranin O and Janus green B. This mixture stained
      nonviable conidia blue, in contrast to viable conidia, which were stained red in
      the cytoplasm and blue in the cell wall. This method may be particularly useful
      for traditional research laboratories, as it provides rapid results using common,
      relatively inexpensive laboratory equipment.

PMID- 24585087
TI  - Surgery or radiosurgery plus whole brain radiotherapy versus surgery or
      radiosurgery alone for brain metastases.
AB  - BACKGROUND: The benefits of adding upfront whole-brain radiotherapy (WBRT) to
      surgery or stereotactic radiosurgery (SRS) when compared to surgery or SRS alone
      for treatment of brain metastases are unclear. OBJECTIVES: To compare the
      efficacy and safety of surgery or SRS plus WBRT with that of surgery or SRS alone
      for treatment of brain metastases in patients with systemic cancer. SEARCH
      METHODS: We searched MEDLINE, EMBASE and The Cochrane Central Register of
      Controlled Trials (CENTRAL) up to May 2013 and annual meeting proceedings of ASCO
      and ASTRO up to September 2012 for relevant studies. SELECTION CRITERIA:
      Randomised controlled trials (RCTs) comparing surgery or SRS plus WBRT with
      surgery or SRS alone for treatment of brain metastases. DATA COLLECTION AND
      ANALYSIS: Two review authors undertook the quality assessment and data
      extraction. The primary outcome was overall survival (OS). Secondary outcomes
      include progression free survival (PFS), local and distant intracranial disease
      progression, neurocognitive function (NF), health related quality of life (HRQL)
      and neurological adverse events. Hazard ratios (HR), risk ratio (RR), confidence
      intervals (CI), P-values (P) were estimated with random effects models using
      Revman 5.1 MAIN RESULTS: We identified five RCTs including 663 patients with one
      to four brain metastases. The risk of bias associated with lack of blinding was
      high and impacted to a greater or lesser extent on the quality of evidence for
      all of the outcomes. Adding upfront WBRT decreased the relative risk of any
      intracranial disease progression at one year by 53% (RR 0.47, 95% CI 0.34 to
      0.66, P value < 0.0001, I(2) =34%, Chi(2) P value = 0.21, low quality evidence)
      but there was no clear evidence of a difference in  OS (HR 1.11, 95% CI 0.83 to
      1.48, P value = 0.47, I(2) = 52%, Chi(2) P value = 0.08, low quality evidence)
      and PFS (HR 0.76, 95% CI 0.53 to 1.10, P value = 0.14, I(2) = 16%, Chi(2) P value
      = 0.28, low quality evidence). Subgroup analyses showed that the effects on
      overall survival were similar regardless of types of focal therapy used, number
      of brain metastases, dose and sequence of WBRT. The evaluation of the impact of
      upfront WBRT on NF, HRQL and neurological adverse events was limited by the
      unclear and high risk of reporting, performance and detection bias, and
      inconsistency in the instruments and methods used to measure and report results
      across studies. AUTHORS' CONCLUSIONS: There is low quality evidence that adding
      upfront WBRT to surgery or SRS decreases any intracranial disease progression at
      one year. There was no clear evidence of an effect on overall and progression
      free survival. The impact of upfront WBRT on neurocognitive function, health
      related quality of life and neurological adverse events was undetermined due to
      the high risk of performance and detection bias, and inconsistency in the
      instruments and methods used to measure and report results across studies.

PMID- 24585088
TI  - Work-related stress, job resources, and well-being among psychiatrists and other
      medical specialists in Finland.
AB  - OBJECTIVES: Previous studies suggest that psychiatrists may be more stressed than
      other medical specialists and mental health professionals. This study examined
      differences in stress factors, job resources, psychological distress, and job
      satisfaction between psychiatrists and other medical specialists. In addition,
      the study examined whether stress factors or job resources accounted for possible
      differences between the groups in psychological distress or job satisfaction.
      METHODS: In 2010, the authors obtained cross-sectional, Web-based survey data
      from a random sample of 2,776 Finnish physicians, including 1,647 women (59%),
      ranging in age from 25 to 69 years old. Comparisons between the two groups used
      analyses of covariance adjusted for gender, age, and employment sector. RESULTS:
      Psychiatrists were less satisfied with their jobs, felt more stressed about
      patients, and experienced more psychological distress compared with other medical
      specialists. However, psychiatrists had more opportunities to control their jobs
      and better team climate compared with other medical specialists. High
      psychological distress among psychiatrists was partly accounted for by high
      patient-related stress. The differences in psychological distress and job
      satisfaction between the two groups were not accounted for by work-family
      conflicts or optimism. CONCLUSIONS: It is important to try to alleviate the high
      levels of patient-related stress among psychiatrists and to further increase
      their job resources. Doing so may enhance the attractiveness of psychiatry as a
      specialty choice.

PMID- 24585089
TI  - Association of heme oxygenase-1 with the risk of polycystic ovary syndrome in non
      obese women.
AB  - STUDY QUESTION: Is circulating heme oxygenase-1 (HO-1) associated with the risk
      of polycystic ovary syndrome (PCOS)? SUMMARY ANSWER: Lower circulating HO-1 is
      associated with a higher risk of PCOS in non-obese women, in a dose-related
      manner. WHAT IS KNOWN ALREADY: PCOS is one of the most common endocrine disorders
      in women of reproductive age, with increasing worldwide incidence. HO-1 plays a
      crucial role in many physiological systems, with potent anti-inflammatory,
      antioxidant and antimetabolic properties. STUDY DESIGN, SIZE, DURATION: This
      hospital-based case-control study included 80 women with PCOS and 80 healthy
      control women seen at the Reproductive Center of Tongji Hospital (Wuhan, China)
      from November 2011 to May 2012. Cases and controls were frequency-matched on age
      and BMI and were enrolled into the study once written informed consent had been
      obtained. PARTICIPANTS/MATERIALS, SETTING, METHODS: Serum hormones, glucose,
      insulin and lipid concentrations were measured using an automated platform.
      Correlation coefficients and multiple linear regression models were calculated in
      the combined group (both cases and controls) using serum HO-1 concentration as
      the independent variable and age and BMI as covariate variables to explore the
      association between HO-1 and the pathophysiology of PCOS. To examine the
      independent association of serum HO-1 levels with the likelihood of PCOS,
      multivariate logistic analysis was used. The strength of the association was
      tested further by receiver-operating characteristic (ROC) curve models, with or
      without the addition of HO-1. MAIN RESULTS AND THE ROLE OF CHANCE: Compared with
      controls, women with PCOS were found to have significantly increased insulin
      resistance (IR), oxidative stress (OS) and inflammation levels, creating a
      vicious circle of effects in the pathophysiology of PCOS. However, serum HO-1 was
      negatively associated with this vicious circle. Women with the highest tertile of
      HO-1 (>=5.29 ng/ml) had an odds ratio (OR) of PCOS of 0.02 (95% CI 0.0034-0.07)
      compared with women with the lowest quartile (<3.14 ng/ml) (P < 0.01). This trend
      remained after adjustment for potential confounders in the multivariable model
      (all P < 0.01). ROC analysis based on an existing prognostic model yielded
      significantly discriminative values for PCOS, with or without the addition of HO
      1 (areas under the curves were 0.86 (95% CI 0.81-0.92) versus 0.95 (95% CI 0.92
      0.98); P for difference = 0.0005). LIMITATIONS, REASONS FOR CAUTION: It is
      difficult to establish a time-integrated measure of circulating HO-1 during the
      progression of PCOS and these findings should be confirmed in large-scale studies
      involving different ethnic groups. Moreover, the study lacks measurements of
      glycated hemoglobin (HbA1c) to provide an index of blood glucose concentrations
      over time. WIDER IMPLICATIONS OF THE FINDINGS: Circulating HO-1 that provides
      protection against IR, OS and chronic inflammation is markedly reduced in non
      obese women with PCOS. Low serum HO-1 is suggested as an independent risk factor
      for PCOS; thus, circulating HO-1 levels may be a novel biomarker for PCOS in
      young, non-obese women. STUDY FUNDING/COMPETING INTEREST(S): This work was
      supported by grants from the National Natural Science Foundation of China
      (81202210) and the National Science and Technology Support Program of China
      (2012BAI02B02). None of the authors has any conflict of interest to declare.

PMID- 24585091
TI  - Protective effects of crocin on hemodynamic parameters and infarct size in
      comparison with vitamin E after ischemia reperfusion in isolated rat hearts.
AB  - Although reperfusion is a useful method for the survival of ischemic heart,
      harmful effects have been observed. This study was carried out to investigate the
      preconditioning and cardioprotective potential effects of crocin and vitamin E on
      the hemodynamic and infarct size in the ischemia-reperfusion model of isolated
      rat hearts. Animals were divided into a control group, an ischemia-reperfusion
      control group and three treatment groups: crocin (10, 20, and 40 mg/kg), vitamin
      E (100 mg/kg), and combination (crocin 40 mg/kg with vitamin E 100 mg/kg). The
      hearts were excised, quickly transferred to a Langendorff apparatus, and
      subjected to 30 min of global ischemia followed by 60 min of reperfusion. Left
      ventricular developed pressure, coronary perfusion pressure, left ventricular
      systolic pressure, myocardial contractility, rate pressure product, coronary
      flow, and infarct size were assessed. The successful induction of ischemia was
      determined by ST elevation on the electrocardiogram.The results showed that
      crocin significantly improved cardiac dysfunction and also reduced infarct size
      in the rat hearts. However, the combination of crocin 40 mg/kg and vitamin E 100
      mg/kg had an even more significantly improved effect on the hemodynamic
      parameters and infarct size.Therefore, it can be suggested that the protective
      role of crocin may be due to the stability or reinforcement of antioxidant
      systems, and crocin could be useful for the treatment or prevention of cardiac
      dysfunction.

PMID- 24585094
TI  - Static (1)H dynamic nuclear polarization with the biradical TOTAPOL: a transition
      between the solid effect and the cross effect.
AB  - To study the solid state (1)H-DNP mechanism of the biradical TOTAPOL under static
      conditions the frequency swept DNP enhancement spectra of samples containing 20
      mM and 5 mM TOTAPOL were measured as a function of MW irradiation time and
      temperature. We observed that under static DNP conditions the biradical TOTAPOL
      behaves similar to the monoradical TEMPOL, in contrast to MAS DNP where TOTAPOL
      is considerably more effective. As previously done for TEMPOL, the TOTAPOL DNP
      spectra were analyzed taking a superposition of a basic SE-DNP lineshape and a
      basic CE-DNP lineshape with different amplitudes. The analysis of the steady
      state DNP spectra showed that the SE was dominant in the 6-10 K range and the CE
      was dominant above 10 K. DNP spectra obtained as a function of MW irradiation
      time allowed resolving the individual SE and CE buildup times. At low
      temperatures the SE buildup time was faster than the CE buildup time and at all
      temperatures the CE buildup time was close to the nuclear spin-lattice relaxation
      time, T1n. Polarization calculations involving nuclear spin-diffusion for a model
      system of one electron and many nuclei suggested that the shortening of the T1n
      for increasing temperatures is the reason why the SE contribution to the overall
      enhancement was reduced. 

PMID- 24585092
TI  - Plant extracts of the family Lauraceae: a potential resource for chemopreventive
      agents that activate the nuclear factor-erythroid 2-related factor 2/antioxidant
      response element pathway.
AB  - Cells and tissues counteract insults from exogenous or endogenous carcinogens
      through the expression of genes encoding antioxidants and phase II detoxifying
      enzymes regulated by antioxidant response element promoter regions. Nuclear
      factor-erythroid 2-related factor 2 plays a key role in regulating the
      antioxidant response elements-target gene expression. Hence, the Nrf2/ARE pathway
      represents a vital cellular defense mechanism against damage caused by oxidative
      stress and xenobiotics, and is recognized as a potential molecular target for
      discovering chemopreventive agents. Using a stable antioxidant response element
      luciferase reporter cell line derived from human breast cancer MDA-MB-231 cells
      combined with a 96-well high-throughput screening system, we have identified a
      series of plant extracts from the family Lauraceae that harbor Nrf2-inducing
      effects. These extracts, including Litsea garrettii (ZK-08), Cinnamomum
      chartophyllum (ZK-02), C. mollifolium (ZK-04), C. camphora var. linaloolifera (ZK
      05), and C. burmannii (ZK-10), promoted nuclear translocation of Nrf2, enhanced
      protein expression of Nrf2 and its target genes, and augmented intracellular
      glutathione levels. Cytoprotective activity of these extracts against two
      electrophilic toxicants, sodium arsenite and H2O2, was investigated. Treatment of
      human bronchial epithelial cells with extracts of ZK-02, ZK-05, and ZK-10
      significantly improved cell survival in response to sodium arsenite and H2O2,
      while ZK-08 showed a protective effect against only H2O2. Importantly, their
      protective effects against insults from both sodium arsenite and H2O2 were Nrf2
      dependent. Therefore, our data provide evidence that the selected plants from the
      family Lauraceae are potential sources for chemopreventive agents targeting the
      Nrf2/ARE pathway. 

PMID- 24585093
TI  - Salivary exoglycosidases as markers of alcohol dependence.
AB  - BACKGROUND: Some salivary markers of alcohol abuse/dependence have been proposed
      so far: aminotransferases, gamma-glutamyltransferase, ethanol, ethyl glucuronide,
      ethyl sulfate, sialic acid, beta-hexosaminidase A, oral peroxidase, methanol,
      diethylene/ethylene glycol, alpha-amylase, clusterin, haptoglobin, heavy/light
      chains of immunoglobulins and transferrin. AIM: To investigate the effect of
      chronic alcohol drinking and smoking on the activity (pKat/ml) and output
      (pKat/min) of salivary lysosomal exoglycosidases: alpha-fucosidase (FUC), alpha
      mannosidase (MAN), beta-galactosidase (GAL), and beta-glucuronidase (GLU), and
      their applicability as markers of alcohol dependence. METHODS: The activity of
      FUC, MAN, GAL and GLU was measured colorimetrically in the saliva of healthy
      social drinkers, alcohol-dependent non-smokers and alcohol-dependent smokers.
      RESULTS: We observed an increased salivary activity of FUC, GAL, GLU and MAN, as
      well as an increased output of GAL and GLU, in comparison with controls. The
      highest increase in the activity/output was found in salivary GLU and MAN (GLU,
      even 7- to 18-fold), and the least in GAL. We found an excellent sensitivity and
      specificity and a high accuracy (measured by the area under the ROC curve) for
      salivary FUC, GLU and MAN activities. The salivary GLU activity positively
      correlated with the number of days of last alcohol intoxication. Salivary
      activity of FUC, GAL and MAN, but not GLU, positively correlated with the
      periodontal parameters such as gingival index and papilla bleeding index.
      CONCLUSIONS: Although we found an excellent sensitivity and specificity as well
      as a high accuracy for the salivary activity of FUC, GLU and MAN, the GLU
      activity seems to be mostly applicable as a marker of chronic alcohol drinking
      (alcohol dependence).

PMID- 24585097
TI  - A capillary electrophoresis-based immobilized enzyme reactor using graphene oxide
      as a support via layer by layer electrostatic assembly.
AB  - A novel capillary electrophoresis (CE)-based immobilized enzyme reactor (IMER)
      using graphene oxide (GO) as a support was developed by using a simple and
      reliable immobilization procedure based on layer by layer electrostatic assembly.
      Using trypsin as a model enzyme, the performance of the fabricated CE-based IMERs
      was evaluated. Various conditions, including trypsin concentration, trypsin
      coating time, number of trypsin layers and buffer pH, were investigated and
      optimized. The Michaelis constant Km (0.24 +/- 0.02 mM) and the maximum velocity
      Vmax (0.32 +/- 0.04 mM s(-1)) were determined using the CE-based IMERs, and the
      values are consistent with those obtained using free trypsin, indicating that
      enzyme immobilized via the proposed approach does not cause a significant
      structural change of the enzyme or any reduction of enzyme activity. The
      presented CE-based IMERs exhibit excellent reproducibility with RSD less than
      2.8% over 20 runs, and still remain 79.5% of the initial activity after five days
      with more than 100 runs. Using the proposed CE-based IMERs, the digestion of
      angiotensin was completed within 3 min, while quite a number of trypstic peptides
      were observed for BSA on-line digestion with an incubation time of 30 min. As
      identified by MS analysis, the online digestion products of BSA using the present
      CE-based IMER are comparable with those obtained using free trypsin digestion for
      12 h incubation. It is indicated that the present immobilization strategy using
      GO as a support is reliable and practicable for accurate on-line analysis and
      characterization of peptides and proteins. 

PMID- 24585095
TI  - Spautin-1, a novel autophagy inhibitor, enhances imatinib-induced apoptosis in
      chronic myeloid leukemia.
AB  - Imatinib mesylate (IM), a targeted competitive inhibitor of the BCR-ABL tyrosine
      kinase, has revolutionized the clinical treatment of chronic myeloid leukemia
      (CML). However, resistance and intolerance are still a challenge in the treatment
      of CML. Autophagy has been proposed to play a role in IM resistance. To
      investigate the anti-leukemic activity of specific and potent autophagy inhibitor
      1 (spautin-1) in CML, we detected its synergistic effect with IM in K562 and CML
      cells. Our results showed that spautin-1 markedly inhibited IM-induced autophagy
      in CML cells by downregulating Beclin-1. Spautin-1 enhanced IM-induced CML cell
      apoptosis by reducing the expression of the anti-apoptotic proteins Mcl-1 and Bcl
      2. We further demonstrated that the pro-apoptotic activity of spautin-1 was
      associated with activation of GSK3beta, an important downstream effector of
      PI3K/AKT. The findings indicate that the autophagy inhibitor spautin-1 enhances
      IM-induced apoptosis by inactivating PI3K/AKT and activating downstream GSK3beta,
      leading to downregulation of Mcl-1 and Bcl-2, which represents a promising
      approach to improve the efficacy of IM in the treatment of patients with CML. 

PMID- 24585098
TI  - Use of synthetic serum-free medium for culture of human dermal fibroblasts to
      establish an experimental system similar to living dermis.
AB  - In this study, we sought to establish a defined experimental system for
      fibroblast growth similar to that of the living dermis. To this end, we evaluated
      the growth and biochemical characteristics of fibroblasts cultured with serum
      free HFDM-1, a finely tuned synthetic medium for human fibroblast culture. Three
      culture conditions were used to grow fibroblasts obtained from primary culture:
      (1) culture with Dulbecco's modified Eagle medium (DMEM) plus 10 % fetal bovine
      serum (serum-supplemented DMEM), (2) culture with DMEM (serum-free DMEM), and (3)
      culture with HFDM-1 (HFDM-1), and fibroblast morphology, growth, collagen type I
      production, and lipid composition were analyzed. Fibroblasts grown in HFDM-1
      maintained cell numbers at nearly 100 % from days 14 to 21 and produced more
      collagen type I than cells grown in serum-supplemented and serum-free DMEM.
      Arachidonic acid (20:4) and total polyunsaturated fatty acids were lower in cells
      grown in serum-free DMEM and HFDM-1 than in serum-supplemented DMEM. These
      results suggested that HFDM-1 recapitulated growth conditions in the dermis
      better than traditional, serum-supplemented DMEM. In addition, the controlled
      chemical composition of HFDM-1 eliminated a potential source of variability in
      cell culture conditions. 

PMID- 24585099
TI  - Natural history of vertically acquired HCV infection and associated autoimmune
      phenomena.
AB  - The natural history of vertically acquired HCV infection is ill defined. The aim
      of this study was to outline the natural course of vertical HCV infection in a
      cohort of untreated children, including rate of spontaneous viral clearance,
      frequency and features of HCV-related autoimmune disorders. Children with
      vertical HCV infection were prospectively followed from the first month of life
      with regular clinical and laboratory assessments. Statistical analysis was
      performed using Prism 5.0. Forty-five children (median age 12 years,
      interquartile range 6.9-15.5) were studied. Genotype 1 was predominant (53.3 %).
      Spontaneous viral clearance was achieved by 12 patients (26.7 %) and associated
      with genotype 3. Alanine-amino-transferase levels were increased in most children
      in the first 2 years of life with higher values in those who later cleared the
      infection. All children were asymptomatic for liver disease. Transient
      elastography (32 patients) showed mild or moderate fibrosis in nine and two
      cases, respectively. Non-organ-specific autoantibodies were detected in 24
      children (53.3 %) independently of viremia; of these, one developed type-1
      diabetes. Cryoglobulinemia was associated with genotype 1 infection and found in
      15 subjects (33.3 %): two had low C4 levels and persistent proteinuria.
      CONCLUSIONS: Vertically acquired HCV infection may result in spontaneous
      clearance in up to 27 % of children. Resolution of infection is higher with
      genotype 3, usually occurs in preschool age and persists over time. Chronic
      infection is generally asymptomatic, although hepatomegaly and mild fibrosis may
      develop. Autoantibodies and cryoglobulins are frequent, whereas the associated
      clinical manifestations are rare.

PMID- 24585100
TI  - Role of BAFF in pediatric patients with allergic rhinitis during sublingual
      immunotherapy.
AB  - Sublingual immunotherapy (SLIT) is the only therapeutic option for allergic
      rhinitis (AR) that modifies the immunological process to an allergen, rather than
      treating symptoms simply. However, its regulatory mechanisms are largely unknown.
      B-cell-activating factor of the TNF family (BAFF) plays very important roles in
      the development, differentiation, and proliferation of B cells and T cells. The
      aim of this study was to identify the role of BAFF during SLIT in pediatric
      patients with AR. Seventy-two house dust mite (HDM)-sensitized pediatric patients
      with AR were enrolled in this study. Thirty-six pediatric patients received HDM
      allergen extract for SLIT and 36 pediatric patients received placebo. Serum and
      nasal aspirate of different time points during treatment was collected and used
      for enzyme-linked immunosorbent assay (ELISA) of BAFF and related cytokines,
      respectively. Peripheral blood mononuclear cells were collected and stimulated by
      HDM allergen with or without rhBAFF after 12 months of treatment. Our results
      showed that the expression of BAFF protein decreased during the SLIT treatment
      compared with that in the placebo group after 6 months of therapy, and this trend
      lasted for 12 months. The decreased BAFF expression was positively related to Th2
      cytokines and increased IL-10 expression. BAFF was also related to local
      production of IgA. In vitro experiments showed that BAFF can promote Th2
      cytokines and inhibit IL-10 expression by PBMCs. CONCLUSION: During SLIT, BAFF
      expression was decreased and related to low Th2 cytokine expression and enhanced
      IL-10 expression. Besides, BAFF may contribute to local production of IgA. Our
      results suggested that BAFF may be an important biomarker during SLIT. Authors'
      summary. Sublingual immunotherapy (SLIT) is the only therapeutic option for
      allergic rhinitis (AR) that modifies the immunological process to an allergen,
      rather than simply treating symptoms. However, its regulatory mechanisms are
      largely unknown. B-cell-activating factor of the TNF family (BAFF) plays very
      important roles in the development, differentiation, and proliferation of B cells
      and T cells. Our results showed that during SLIT, BAFF expression was decreased
      and related to low Th2 cytokine expression and enhanced IL-10 expression.
      Besides, BAFF may contribute to local production of IgA. Our results suggested
      that BAFF may be an important biomarker during SLIT.

PMID- 24585101
TI  - Terbium promotes adhesion and osteogenic differentiation of mesenchymal stem
      cells via activation of the Smad-dependent TGF-beta/BMP signaling pathway.
AB  - With its special physical and chemical properties, terbium has been widely used,
      which has inevitably increased the chance of human exposure to terbium-based
      compounds. It was reported that terbium mainly deposited in bone after
      introduction into the human body. Although some studies revealed the effects of
      terbium on bone cell lines, there have been few reports about the potential
      effect of terbium on adhesion and differentiation of mesenchymal stem cells
      (MSCs). In this study, we investigated the effects of terbium on the adhesion and
      osteogenic and adipogenic differentiation of MSCs and the associated molecular
      mechanisms. Our data reveal that terbium promoted the osteogenic differentiation
      in a time-dependent manner and conversely inhibited the adipogenic
      differentiation of MSCs. Meanwhile, the cell-cell or cell-matrix interaction was
      enhanced by activating adherent-related key factors, which were evaluated by real
      time reverse transcriptase polymerase chain reaction (RT-PCR). Real-time RT-PCR
      and Western blot analysis were also performed to further detect osteogenic and
      adipogenic biomarkers of MSCs. The regulation of terbium on differentiation of
      MSCs led to the interaction between the transforming growth factor beta/bone
      morphogenetic protein and peroxisome-proliferator-activated receptor gamma
      (PPARgamma) signaling pathways, resulting in upregulation of the osteogenic
      master transcription factors, such as Runt-related transcription factor 2, bone
      morphogenetic protein 2, collagen I, alkaline phosphatase, and osteocalcin, and
      downregulation of the adipogenic master transcription factors, such as
      PPARgamma2. The results provide novel evidence to elucidate the mechanisms of
      bone metabolism by terbium and may be helpful for more rational application of
      terbium-based compounds in the future.

PMID- 24585102
TI  - The class Ib ribonucleotide reductase from Mycobacterium tuberculosis has two
      active R2F subunits.
AB  - Ribonucleotide reductases (RNRs) catalyze the reduction of ribonucleotides to
      their corresponding deoxyribonucleotides, playing a crucial role in DNA repair
      and replication in all living organisms. Class Ib RNRs require either a diiron
      tyrosyl radical (Y.) or a dimanganese-Y. cofactor in their R2F subunit to
      initiate ribonucleotide reduction in the R1 subunit. Mycobacterium tuberculosis,
      the causative agent of tuberculosis, contains two genes, nrdF1 and nrdF2,
      encoding the small subunits R2F-1 and R2F-2, respectively, where the latter has
      been thought to serve as the only active small subunit in the M. tuberculosis
      class Ib RNR. Here, we present evidence for the presence of an active Fe 2 (III) 
      Y. cofactor in the M. tuberculosis RNR R2F-1 small subunit, supported and
      characterized by UV-vis, X-band electron paramagnetic resonance, and resonance
      Raman spectroscopy, showing features similar to those for the M. tuberculosis R2F
      2-Fe 2 (III) -Y. cofactor. We also report enzymatic activity of Fe 2 (III) -R2F-1
      when assayed with R1, and suggest that the active M. tuberculosis class Ib RNR
      can use two different small subunits, R2F-1 and R2F-2, with similar activity.

PMID- 24585103
TI  - Tribal Veterans Representative (TVR) training program: the effect of community
      outreach workers on American Indian and Alaska Native Veterans access to and
      utilization of the Veterans Health Administration.
AB  - American Indians and Alaska Natives serve at the highest rate of any US race or
      ethnic group, yet are the most underserved population of Veterans and do not take
      advantage of the Department of Veterans Affairs (VA) benefits and services.
      Barriers to seeking care include stigma, especially for mental health issues;
      distance to care; and lack of awareness of benefits and services they are
      entitled to receive. In response to this underutilization of the VA, an
      innovative program--the Tribal Veterans Representative (TVR) program--was
      developed within the VA to work with American Indians and Alaska Natives in rural
      and remote areas. The TVR goes through extensive training every year; is a
      volunteer, a Veteran and tribal community member who seeks out unenrolled Native
      Veterans, provides them with information on VA health care services and benefits,
      and assists them with enrollment paperwork. Being from the community they serve,
      these outreach workers are able to develop relationships and build rapport and
      trust with fellow Veterans. In place for over a decade in Montana, this program
      has enrolled a countless number of Veterans, benefiting not only the individual,
      but their family and the community as well. Also resulting from this program, are
      the implementation of Telemental Health Clinics treating Veterans with PTSD, a
      transportation program helping Veterans get to and from distant VA facilities, a
      Veteran Resource Center, and a Veteran Tribal Clinic. This program has
      successfully trained over 800 TVRs, expanded to other parts of the country and
      into remote areas of Alaska.

PMID- 24585104
TI  - Exploring ethnic and racial differences in falls among older adults.
AB  - Falls are common events that threaten the independence and health of older
      adults. Studies have found a wide range of fall statistics in different ethnic
      and racial groups throughout the world. These studies suggest that fall rates may
      differ between different racial and ethnic groups. Studies also suggest that the
      location of falls, circumstances of falls, and particular behaviors may also be
      different by population. Also migration to new locations may alter an
      individual's fall risk. However, there are few studies that directly compare
      ethnic and racial differences in falls statistics or examine how known fall risk
      factors change based on race and ethnicity. This paper reviews the existing
      literature on how falls may differ between different racial and ethnic groups,
      highlights gaps in the literature, and explores directions for future research.
      The focus of this paper is community dwelling older adults and immigrant
      populations in the United States. 

PMID- 24585105
TI  - Cilostazol in acute myocardial infarction: new tricks for an old drug?

PMID- 24585106
TI  - Infective endocarditis: therapeutic options and indications for surgery.
AB  - Infective endocarditis is a serious, life-threatening condition with mortality of
      30% at one year. Established treatment is a combination of anti-microbial therapy
      and close interface between multiple specialist teams of cardiologists,
      microbiologists and cardiac surgeons to ensure availability of early surgery to
      those patients who require it. There are evidence-based established indications
      for surgery and a shifting body of evidence advocating earlier surgical
      intervention. The development of complications is often the driving cause of
      referral for surgical intervention. Here we discuss the management of infective
      endocarditis, considering both antimicrobial therapy and indications for surgery
      to treat this debilitating disease.

PMID- 24585107
TI  - Assessing clinical impact of myocardial perfusion studies: ischemia or other
      prognostic indicators?
AB  - One of the major strengths of nuclear myocardial perfusion imaging (MPI) is the
      robust prognostic databases from observational studies demonstrating
      significantly different outcomes in patients with low-risk vs high-risk scans.
      The severity of the MPI defect can be semi-quantitated using the summed stress
      score (SSS) and summed difference score (SDS). SSS is more strongly associated
      with mortality, whereas SDS is the better predictor of subsequent coronary
      angiography and revascularization. The strength of MPI variables as prognostic
      indicators decreases when adjusted for prognostically important clinical and
      stress test variables. Nonetheless, most studies of general patient populations
      have demonstrated that MPI adds incremental prognostic value to clinical and
      stress test information. In contrast to these positive results from observational
      studies, the application of MPI ischemia as a treatment guide in several recent
      trials (DIAD, WOMEN, COURAGE, BARI 2D, STICH) has largely failed to identify
      patient subsets with improved outcome. This issue will continue to be
      investigated in the ongoing PROMISE and ISCHEMIA trials. 

PMID- 24585108
TI  - Novel molecular angiotensin converting enzyme and angiotensin receptor imaging
      techniques.
AB  - Angiotensin II (AII), an octapeptide member of the renin-angiotensin system
      (RAS), is formed by the enzyme angiotensin converting enzyme (ACE) and exerts
      adverse cellular effects through an interaction with its type 1 receptor (AT1R).
      Both ACE inhibitors and angiotensin receptor blockers (ARB) mitigate the
      vasoconstrictive, proliferative, proinflammatory, proapoptotic, and profibrotic
      effects of AII and are widely used as effective anti-remodeling agents in
      clinical practice. Prediction of individual response to these agents, however,
      remains problematic and is influenced by many factors including race, gender, and
      genotype. In addition, systemic and tissue RAS activity do not correlate closely.
      This report summarizes the results of on-going attempts to noninvasively
      determine tissue ACE activity and AT1R expression using novel nuclear tracers. It
      is hoped that the availability of such imaging techniques improve treatment of
      heart failure through more selective pharmacologic intervention and better dose
      titration of available drugs. 

PMID- 24585109
TI  - Endogenous sex hormones, metabolic syndrome, and diabetes in men and women.
AB  - Endogenous sex hormones predict impairments of glucose regulation. Cross
      sectional studies suggest that lower levels of testosterone in men and higher
      levels in women increase risk of metabolic syndrome and diabetes, whereas lower
      levels of sex hormone binding globulin in both men and women increase risk of
      metabolic syndrome and diabetes. In a systematic review, we summarize existing
      longitudinal studies, which suggest similar patterns. However, these studies are
      often limited to a single sex steroid measure. Whether these associations are
      primarily a marker of adiposity, and whether these associations differ between
      younger eugonadal vs older hypogonadal adults is also uncertain. The impact of
      exogenous sex steroid therapy may not reflect relationships between sex hormones
      and impaired glucose regulation that occur without supplementation. Therefore,
      examination of endogenous sex steroid trajectories and obesity trajectories
      within individuals might aid our understanding of how sex steroids contribute to
      glucose regulation. 

PMID- 24585110
TI  - The practical role of echocardiography in selection, implantation, and management
      of patients requiring LVAD therapy.
AB  - Viable treatment options for advanced heart failure have not emerged as the
      number of people afflicted with this condition has grown. Although heart
      transplantation is the only curative strategy for patients with end-stage heart
      failure, the relative shortage of donors has led to a worldwide plateau of this
      option over the past 20 years. The result is an unacceptably high mortality rate
      among patients with advanced heart failure. Interest in developing alternative
      curative strategies based on chronic circulatory support, with the aim of
      prolonging and improving quality of life for these patients, has grown. Patients
      supported with left ventricular assist devices require structured longitudinal
      care from a team of providers. An integrated approach using basic
      echocardiography is critical to patient selection, implantation, and continued
      surveillance and success of patients with left ventricular assist devices.

PMID- 24585111
TI  - Same day discharge after elective percutaneous coronary intervention.
AB  - Same-day percutaneous coronary intervention (PCI) is a reality with modern
      interventional equipment and pharmaceutical agents. Elective PCI is rarely an
      inpatient procedure and is now predominantly considered an outpatient procedure.
      Approaches to safely manage elective patients through same-day PCI have been well
      described in the literature and demonstrate no safety signal compared with
      overnight monitoring in the elective patient. With the costs of elective PCI
      being time dependent in comparison to fixed reimbursement of outpatient care, the
      efficiencies to bed utilization offered by same-day PCI make this attractive from
      an efficiency view point. Patient satisfaction improves with same-day discharge.
      The potential for cost-efficient care can only be maximized if health care
      providers view this shift to outpatient PCI care as an impetus to improve the
      whole care process rather than an administrative change with no effect on actual
      patient care. Same-day PCI is effective and can be integrated into modern health
      care. 

PMID- 24585112
TI  - Making sense of high sensitivity troponin assays and their role in clinical care.
AB  - Cardiac troponin assays have an established and undisputed role in the diagnosis
      and risk stratification of patients with acute myocardial infarction. As troponin
      assays gets more sensitive and more precise, the number of potential uses has
      rapidly expanded, but the use of this test has also become more complicated and
      controversial. Highly sensitive troponin assays can now detect troponin levels in
      most individuals, but accurate interpretation of these levels requires a clear
      understanding of the assay in the context of the clinical scenario. This paper
      provides a practical and up-to-date overview of the uses of highly sensitive
      troponin assays for diagnosis, prognosis, and risk stratification in clinical
      practice. 

PMID- 24585113
TI  - Assessing the prognostic implications of myocardial perfusion studies:
      identification of patients at risk vs patients who may benefit from intervention?
AB  - Stress myocardial perfusion imaging (MPI) has a well-established role in
      improving risk stratification. Recent analyses, compared with older data, suggest
      that the yield of stress MPI has decreased. In part, this trend relates to
      testing patients with heterogeneous, but improved, risk factor modification. In
      this setting, positron emission tomography with myocardial flow reserve enhances
      risk stratification as it reflects the end result of atherosclerosis. Recent
      studies have also emphasized the clinical impact of incremental risk
      stratification by assessing net reclassification improvement (NRI). Previous
      retrospective studies have favored an ischemic threshold to select patients that
      benefit from revascularization, but this finding has not been corroborated in
      randomized trials. However, no large randomized trial has directly tested a
      strategy of revascularization for patients with at least a moderate amount of
      ischemia at risk. Unfortunately, even when faced with a significantly abnormal
      MPI result, subsequent action is too often absent. 

PMID- 24585114
TI  - Health-related quality of life after transcatheter or surgical aortic valve
      replacement in high-risk patients with severe aortic stenosis: an updated review
      of literature.
AB  - Recent trials have highlighted the comparable mortality benefits and durability
      of the results for patients with severe aortic stenosis (AS) and high surgical
      risk managed with either transcatheter aortic valve replacement (TAVR) or
      surgical aortic valve replacement (AVR). Various national guidelines and
      international regulatory bodies have approved TAVR, thereby leading to potential
      wide usage and dissemination of this technique worldwide. Quality-of-life
      outcomes, in spite of being an important measure of success and acceptability of
      the procedure, have not been publicized as extensively. For high risk patients
      with severe AS, implementation of TAVR has resulted in comparable survival, but
      different and novel adverse events compared with AVR. We present an updated
      review focusing on the quality-of-life outcomes and issues with this new and
      important procedural approach. 

PMID- 24585116
TI  - [Conservative treatment in male urinary incontinence].
AB  - Prevalence, pathophysiology, diagnostic and therapeutic approaches of urinary
      incontinence are well studied in women; however, studies on male urinary
      incontinence focus on incontinence following surgery of the bladder or prostate,
      predominantly incontinence after radical prostatectomy. Aging men suffer from
      incontinence, most frequently urge incontinence (overactive bladder, OAB), nearly
      as often as women do.The domain of conservative therapy of urinary stress
      incontinence in men is pelvic floor training. It remains unclear whether
      biofeedback procedures, electrostimulation therapy, or magnetic stimulation
      therapy can enhance pelvic floor training. There are data suggesting that an off
      label therapy with Duloxetin(r), a selective serotonin-noradrenaline reuptake
      inhibitor (SSNRI), improves urinary incontinence following radical prostatectomy.
      Antimuscarinic agents in combination with bladder training have been proven as
      safe and effective treatment in men with OAB. Data, however, suggest that men
      with OAB are far less frequently treated than women.

PMID- 24585117
TI  - [Hypospadia and infertility of Henry II of France (1519-1559)].
AB  - Henry II (1519-1559) of France was the second son of Francis I (1494-1547) and
      Claude de France (1498-1524) born in 1519 in St. Germain-en-Laye. After his older
      brother's and his father's death in 1547, he was anointed the French king in
      Reims. In 1533 already, as a 14-year-old boy, for reasons of state, he was
      married to the same aged Catherine de Medici (1519-1589), as her uncle was Pope
      Clement VII (1478-1534). The marriage remained childless for 11 years since
      Henry, due to a distinct hypospadia and a completely sexually inexperienced wife
      was unable to conceive children with her. His existing liaison to Diane de
      Poitiers (1499-1566) - a 19-year-older maid of honor of his father Francis I from
      1537 until his death - influenced his sexual life immensely.The blame for the
      childless marriage was placed primarily on his wife, as Henry had become father
      of an illegitimate daughter with a mistress. Catherine then underwent all
      possible medical and alchemical procedures to finally give birth to the hoped
      Dauphin. Ironically, her rival for the favor of her husband, Diane de Poitiers
      was one of her greatest allies. She made clear that the cause lay with Henry and
      not with his wife. This was confirmed by the added solid physician Jean Fernel
      (1497-1558). His treatment of Henry and the simultaneous training of the
      unexperienced Catherine by Diane de Poitiers led to success.The result was the
      birth of Francis II (1544-1560) in 1544, the first of 10 children in 12 years.
      Thus, the dynasty was saved. After the death of Henry in a tragic tournament
      accident in 1559, three of his sons became kings of France. But the line of
      Valois remained without further descendants and was continued by Henry IV, the
      first Bourbon king in 1589.

PMID- 24585127
TI  - [Arthroplasty of the Femoropatellar Joint - What Data are Available?].
AB  - BACKGROUND: Osteoarthritis of the knee joints is rarely seen only in the
      femoropatellar joint. In isolated severe osteoarthritis of the femoropatellar
      joint an isolated prosthetic joint replacement of this joint is indicated. To
      achieve good results, correct patient selection with no arthritis in the
      femorotibial joint and absence of maltracking and instability of the patella are
      crucial. Modern prostheses with a femoral onlay component and a proper surgical
      technique with correct alignment of the prosthetic component and prevention of an
      overstuffing of the patella are essential. PATIENTS AND METHODS: Fifty-three
      Vanguard Prostheses (Biomet GmbH, Warsaw, IL) were examined after a follow-up of
      3.7 +/- 2.8 (1-8) years. RESULTS: The Knee Society score increased from 117.3
      points preoperative to 181.2 points at the follow-up. One knee was revised
      because of neuropathic pain. Two patients suffered from periprosthetic patellar
      fractures after falling. CONCLUSION: In well indicated cases with isolated
      osteoarthritis of the femoropatellar joint, good clinical results with a
      femoropatellar prosthesis can be expected.

PMID- 24585128
TI  - Translation, cross-cultural adaptation and validation of the Bulgarian version of
      the Dizziness Handicap Inventory.
AB  - PURPOSE: The aim of the present study was the translation, cross-cultural
      adaptation and validation of the Dizziness Handicap Inventory in Bulgarian
      language (DHI-BG). METHODS: Ninety-seven vestibular patients (19 men and 78
      women, mean age 45.08 +/- 13.85 years) took part in the investigation. All
      participants were asked to fill in the DHI-BG. Internal consistency was estimated
      using Cronbach's alpha and item-total correlation, reproducibility by calculating
      Bland-Altman's limits of agreement and intraclass correlation coefficients
      (ICCs). Associations were estimated by Spearman's correlation coefficients.
      RESULTS: The Cronbach's alpha for the total score, functional, physical and
      emotional subscales of DHI-BG were 0.88, 0.75, 0.72 and 0.81. The floor and
      ceiling effects of the DHI-BG total scale were evaluated with respect to the
      limits of agreement which were +/-9.4-14.53 points. Intraclass correlation
      coefficients (ICCs) for all scale and subscales were higher than the recommended
      value of 0.75 and determined good test-retest reliability. The range of items
      correlation for DHI-BG was from 0.27 (item 12) to 0.72 (item 3). No significant
      differences were observed in the Cronbach's alpha coefficients between the DHI-BG
      and the original version, the German and Italian versions of the questionnaire.
      The most significant difference was observed in comparison with the German
      version of DHI. Construct validity presented a moderate correlation between
      Romberg coefficients and DHI-BG scores and strong correlation between all scores
      of DHI and the self-perceived disability. The results suggest that DHI-BG scores
      show a good discriminative validity between groups with different levels of self
      assessed disability. CONCLUSION: The Bulgarian version of the DHI is a reliable
      and valid tool in assessing the impact of dizziness on the quality of life in
      Bulgarian vestibular patients.

PMID- 24585129
TI  - Measuring individual quality of life in patients receiving radiation therapy: the
      SEIQoL-Questionnaire.
AB  - PURPOSE: Quality of life (QoL) is one of the most important outcomes in cancer
      care. Although a number of instruments to measure health-related QoL (HRQoL)
      exist, there are few suitable instruments to measure individual QoL. The best
      established instrument is the Schedule for the Evaluation of Individual Quality
      of Life (SEIQoL). The disadvantage of this questionnaire is its use of semi
      structured interviews, which are very time-consuming. The purpose of our study
      was to transform the SEIQoL into an economical instrument that can be used in
      clinical trials with large samples. METHODS: We developed the SEIQoL
      Questionnaire (SEIQoL-Q) on the basis of the SEIQoL-Direct Weighting (SEIQoL-DW)
      by transforming the interview guide into a written questionnaire. Patients (N =
      1,108) in all three phases of radiation treatment (first consultation, ongoing
      irradiation, and aftercare) were asked to complete the SEIQoL-Q and the European
      Organization for Research and Treatment of Cancer QLQ-C30. RESULTS: While the
      average HRQoL measured by the QLQ-C30 was 55.6, the average SEIQoL-Q index was
      59.6. The most important life domain was "physical health," followed by
      "emotional well-being" and "family." Patients attributed the highest level of
      satisfaction to "home/housing," followed by "family" and "partnership." Male
      patients were shown to have a significantly better QoL than females. The SEIQoL-Q
      index correlates moderately with the QLQ-C30 functioning scale "global quality of
      life" [r = .42 (p < .001)]. CONCLUSIONS: According to our findings, the SEIQoL-Q
      appears to be a feasible and economical instrument for use in quantitative
      research among cancer patients in different stages of their disease.

PMID- 24585132
TI  - Safety issues now have a greater prominence within nuclear cardiology when
      compared to other modalities that do not expose patients to ionizing radiation.

PMID- 24585130
TI  - Antibiotics for acute bronchitis.
AB  - BACKGROUND: The benefits and risks of antibiotics for acute bronchitis remain
      unclear despite it being one of the most common illnesses seen in primary care.
      OBJECTIVES: To assess the effects of antibiotics in improving outcomes and assess
      adverse effects of antibiotic therapy for patients with a clinical diagnosis of
      acute bronchitis. SEARCH METHODS: We searched CENTRAL 2013, Issue 12, MEDLINE
      (1966 to January week 1, 2014), EMBASE (1974 to January 2014) and LILACS (1982 to
      January 2014). SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing
      any antibiotic therapy with placebo or no treatment in acute bronchitis or acute
      productive cough, in patients without underlying pulmonary disease. DATA
      COLLECTION AND ANALYSIS: At least two review authors extracted data and assessed
      trial quality. MAIN RESULTS: Seventeen trials with 3936 participants were
      included in the primary analysis. The quality of trials was generally good. There
      was limited evidence to support the use of antibiotics in acute bronchitis. At
      follow-up, there was no difference in participants described as being clinically
      improved between antibiotic and placebo groups (11 studies with 3841
      participants, risk ratio (RR) 1.07, 95% confidence interval (CI) 0.99 to 1.15;
      number needed to treat for an additional beneficial outcome (NNTB) 22.
      Participants given antibiotics were less likely to have a cough (four studies
      with 275 participants, RR 0.64, 95% CI 0.49 to 0.85; NNTB 6); have a night cough
      (four studies with 538 participants, RR 0.67, 95% CI 0.54 to 0.83; NNTB 7) and a
      shorter mean cough duration (seven studies with 2776 participants, mean
      difference (MD) -0.46 days, 95% CI -0.87 to -0.04). The differences in presence
      of a productive cough at follow-up and MD of productive cough did not reach
      statistical significance.Antibiotic-treated patients were more likely to be
      unimproved according to clinician's global assessment (six studies with 891
      participants, RR 0.61, 95% CI 0.48 to 0.79; NNTB 25); have an abnormal lung exam
      (five studies with 613 participants, RR 0.54, 95% CI 0.41 to 0.70; NNTB 6); have
      a reduction in days feeling ill (five studies with 809 participants, MD -0.64
      days, 95% CI -1.16 to -0.13) and a reduction in days with limited activity (six
      studies with 767 participants MD -0.49 days, 95% CI -0.94 to -0.04). The
      differences in proportions with activity limitations at follow-up did not reach
      statistical significance. There was a significant trend towards an increase in
      adverse effects in the antibiotic group (12 studies with 3496 participants) (RR
      1.20, 95% CI 1.05 to 1.36; NNT for an additional adverse effect 5). AUTHORS'
      CONCLUSIONS: There is limited evidence to support the use of antibiotics in acute
      bronchitis. Antibiotics may have a modest beneficial effect in some patients such
      as frail, elderly people with multimorbidity who may not have been included in
      trials to date. However, the magnitude of this benefit needs to be considered in
      the broader context of potential side effects, medicalisation for a self-limiting
      condition, increased resistance to respiratory pathogens and cost of antibiotic
      treatment.

PMID- 24585133
TI  - Latitudinal variation in sensitivity of flower bud formation to high temperature
      in Japanese Taraxacum officinale.
AB  - Control of flowering time plays a key role in the successful range expansion of
      plants. Taraxacum officinale has expanded throughout Japan during the 110 years
      after it was introduced into a cool temperate region. The present study tested a
      hypothesis that there is a genetic difference in the bud formation time in
      relation to temperature along latitudinal gradient of T. officinale populations.
      In Experiment 1, plants from three populations at different latitudes (26, 36,
      and 43 degrees N) were grown at three temperatures. Time to flower bud appearance
      did not significantly differ among the three populations when plants were grown
      at 14  degrees C, whereas it increased with increasing latitude when grown at 19
      and 24  degrees C. Rosette diameter was not different among the populations,
      indicating that the variation in bud formation time reflected a difference in
      genetic control rather than size variation. The latitudinal variation in bud
      appearance time was confirmed by Experiment 2 in which plants from 17 population
      were used. In Experiment 3, the size of plants that exhibited late-flowering was
      studied to test a hypothesis that the variation in flowering time reflects
      dormancy of vegetative growth, but the late-flowering plants were found to
      continue growth, indicating that vegetative dormancy was not the cause of the
      variation. The results clearly indicate that the degree of suppression of flower
      bud formation at high temperature decreases with latitude from north to south,
      which is under genetic control. 

PMID- 24585134
TI  - Barriers to and facilitators of physical activity among persons with
      schizophrenia: a survey of physical therapists.
AB  - OBJECTIVE: This study examined the experience, perceptions, and knowledge of
      physical therapists who work within mental health services regarding barriers to
      and facilitators of physical activity among people with schizophrenia. METHODS: A
      total of 151 physical therapists, members of the International Organization of
      Physical Therapists in Mental Health, completed an online survey. Data-driven and
      concept driven content analysis was conducted with the responses. RESULTS: The
      most frequently cited barriers were patients' lack of motivation (45% of
      respondents) and a lack of priority given to physical activity by other health
      care professionals (28%). The most frequently cited facilitators included the
      provision of esteem support by health care professionals (28%) and the promotion
      of enjoyment and autonomy for the patient (25%). CONCLUSIONS: When promoting
      physical activity among individuals with schizophrenia, health care professionals
      who work in mental health settings should provide an individual approach, taking
      into account patient related and situational factors.

PMID- 24585151
TI  - Copper catalysed Ullmann type chemistry: from mechanistic aspects to modern
      development.
AB  - Cu-catalysed arylation reactions devoted to the formation of C-C and C-heteroatom
      bonds (Ullmann-type couplings) have acquired great importance in the last decade.
      This review discusses the history and development of coupling reactions between
      aryl halides and various classes of nucleophiles, focusing mostly on the
      different mechanisms proposed through the years. Selected mechanistic
      investigations are treated more in depth than others. For example, evidence in
      favour or against radical mechanisms is discussed. Cu(I) and Cu(III) complexes
      involved in the Ullmann reaction and N/O selectivity in aminoalcohol arylation
      are discussed. A separate section has been dedicated to the synthesis of
      heterocyclic rings through intramolecular couplings. Finally, recent developments
      in green chemistry for these reactions, such as reactions in aqueous media and
      heterogeneous catalysis, have also been reviewed.

PMID- 24585156
TI  - Response to Ascaridia galli infection in growing chickens in relation to their
      body weight.
AB  - It was hypothesized that chickens with extremely varying body weights (BW) from
      an otherwise homogeneous host sample cope differently with Ascaridia galli
      (Schrank 1788) infection. Small and large birds, falling into either the lower or
      the upper 5% quantiles of BW distribution of a parent stock flock, were selected
      at an age of 4 weeks, housed separately and fed restrictively with the same
      amount of feed. At week 5, all the small and large birds (635 and 1,297 g/bird,
      respectively; P < 0.001) were inoculated with 1,000 A. galli eggs and euthanized
      52 days post-infection. Small birds had higher daily weight gains (P = 0.004) but
      final BWs of larger birds were still higher (P < 0.001) at slaughter. Prevalence,
      intensity of infection as well as worm abundance were higher in small birds when
      compared with the large birds (P < 0.05), whereas plasma concentrations of A.
      galli-specific antibodies and worm length remained unaffected (P > 0.05). In
      conclusion, large birds resist A. galli infection more effectively than do small
      ones, possibly through different mechanisms acting on allocation of available
      nutrient and body reserves under the exposure of the infection.

PMID- 24585157
TI  - Current state of health care reform: dysfunctional government, divided country.

PMID- 24585152
TI  - Effect of aerobic exercise training on arterial stiffness in obese populations :
      a systematic review and meta-analysis.
AB  - BACKGROUND AND OBJECTIVE: Controversy exists as to whether aerobic exercise
      training decreases arterial stiffness in obese subjects. The aim of this study
      was to systematically review and quantify the effect of aerobic exercise training
      on arterial stiffness in obese populations. METHODS: MEDLINE, Cochrane, Scopus,
      and Web of Science were searched up until May 2013 for trials assessing the
      effect of aerobic training interventions lasting 8 weeks or more on arterial
      stiffness in obese populations (body mass index >=30 kg/m(2)). Standardized mean
      difference (SMD) in arterial stiffness parameters (augmentation index, beta
      stiffness, distensibility, pulse wave velocity, arterial waveforms) was
      calculated using a random-effects model. Subgroup and meta-regression analyses
      were used to study potential moderating factors. RESULTS: Eight trials,
      comprising a total of 235 subjects with an age range of 49-70 years, met the
      inclusion criteria. Arterial stiffness was not significantly reduced by aerobic
      training (SMD -0.17; 95 % confidence interval (CI) -0.39, 0.06, P = 0.14).
      Similarly, post-intervention arterial stiffness was similar between the aerobic
      trained and control obese groups (SMD 0.02; 95 % CI -0.28, 0.32, P = 0.88).
      Neither heterogeneity nor publication bias were detected in these analyses. In
      subgroup analyses, arterial stiffness was significantly reduced in aerobic
      trained subgroups having below median values in post- minus pre-intervention
      systolic blood pressure (SBP) (P < 0.01), exercise intensity rating score (P <
      0.01), and methodological quality score (P < 0.01). Equivalent results were
      obtained in meta-regression analyses. CONCLUSION: Based on current published
      trials, arterial stiffness is generally not reduced in middle-aged and older
      obese populations in response to aerobic training. However, in studies using low
      intensity aerobic training and yielding a decrease in SBP, arterial stiffness may
      decrease. Long-term studies are needed to assess the prognostic value of these
      findings.

PMID- 24585159
TI  - Depressed or not depressed: untangling symptoms of depression in patients
      hospitalized with coronary heart disease.
AB  - BACKGROUND: Assessing depression in patients hospitalized with coronary heart
      disease is clinically challenging because depressive symptoms are often
      confounded by poor somatic health. OBJECTIVE: To identify symptom clusters
      associated with clinical depression in patients hospitalized with coronary heart
      disease. METHOD: Secondary analyses of 3 similar data sets for hospitalized
      patients with coronary heart disease who had diagnostic screening for depression
      (99 depressed, 224 not depressed) were done. Depressive symptoms were assessed by
      using the Hamilton Depression Rating Scale or the Beck Depression Inventory.
      Hierarchical cluster analysis was performed on 11 symptom variables: anhedonia,
      dysphoria, loss of appetite, sleep disturbance, fatigue, guilt, suicidal
      symptoms, hypochondriasis, loss of libido, psychomotor impairment, and nervous
      irritability. Associations between symptom clusters and presence or absence of
      clinical depression were estimated by using logistic regression. RESULTS: Fatigue
      (69%) and sleep disturbance (55%) were the most prevalent symptoms. Guilt (25%)
      and suicidal symptoms (9%) were the least common. Three symptom clusters
      (cognitive/affective, somatic/affective, and somatic) were identified. Compared
      with patients without cognitive/affective symptoms, patients with the
      cognitive/affective symptom cluster (anhedonia, dysphoria, guilt, suicidal
      symptoms, nervous irritability) had an odds ratio of 1.41 (P<.001; 95% CI, 1.223
      1.631) for clinical depression. CONCLUSION: Clinicians should be alert for
      clinical depression in hospitalized patients with coronary heart disease who have
      the cognitive/affective symptom cluster.

PMID- 24585160
TI  - Interface pressure at different degrees of backrest elevation with various types
      of pressure-redistribution surfaces.
AB  - BACKGROUND: Increased elevation of the head of the bed is linked to a higher risk
      for sacral pressure ulcers. A semirecumbent position of at least 30 degrees  is
      recommended for the prevention of ventilator-associated pneumonia in patients
      treated with mechanical ventilation. Therefore, prevention of pressure ulcers and
      prevention of pneumonia seem to demand contradictory, possibly incompatible,
      positioning. OBJECTIVES: To measure pressure at the interface between sacral skin
      and the supporting surface in healthy volunteers at different degrees of upright
      position with different types of mattresses. METHODS: An open, prospective,
      randomized crossover trial was conducted with 20 healthy volunteers. Interface
      pressure was measured by using a pressure mapping device with the participant in
      a supine position at 0, 10 degrees , 30 degrees , and 45 degrees  elevation and
      in the reverse Trendelenburg position at 10 degrees  and 30 degrees . Four types
      of mattresses were examined: 2 different foam mattresses and 2 air suspension
      beds, 1 of the latter with low-air-loss technology. RESULTS: Peak sacral
      interface pressures increased significantly only at 45 degrees  of backrest
      elevation (P < .001). A mattress system with low-air-loss technology
      significantly reduced peak interface pressures at all angles (P < .001). The
      reverse Trendelenburg position led to lower peak pressures for all positions (P =
      .01). CONCLUSIONS: Backrest elevation up to 30 degrees  might be a compromise
      between the seemingly incompatible demands of skin integrity and the prevention
      of ventilator-associated pneumonia. The reverse Trendelenburg position and a
      mattress system with low-air-loss technology could be additional useful tools to
      help prevent skin breakdown at the sacrum.

PMID- 24585161
TI  - Continuous bedside pressure mapping and rates of hospital-associated pressure
      ulcers in a medical intensive care unit.
AB  - BACKGROUND: Critically ill patients are vulnerable to the development of hospital
      associated pressure ulcers (HAPUs). Positioning of patients is an essential
      component of pressure ulcer prevention because it off-loads areas of high
      pressure. However, the effectiveness of such positioning is debatable. A
      continuous bedside pressure mapping (CBPM) device can provide real-time feedback
      of optimal body position though a pressure-sensing mat that displays pressure
      images at a patient's bedside, allowing off-loading of high-pressure areas and
      possibly preventing HAPU formation. METHODS: A prospective controlled study was
      designed to determine if CBPM would reduce the number of HAPUs in patients
      treated in our medical intensive care unit. In 2 months, 422 patients were
      enrolled and assigned to beds equipped with or without a CBPM device. Patients'
      skin was assessed daily and weekly to determine the presence and progress of
      HAPUs. All patients were turned every 2 hours. CBPM patients were repositioned to
      off-load high-pressure points during turning, according to a graphic display. The
      number of newly formed HAPUs was the primary outcome measured. A chi(2) test was
      then used to compare the occurrence of HAPUs between groups. RESULTS: HAPUs
      developed in 2 of 213 patients in the CBPM group (0.9%; both stage II) compared
      with 10 of 209 in the control group (4.8%; all stage II; P = .02). CONCLUSION:
      Significantly fewer HAPUs occurred in the CBPM group than the control group,
      indicating the effectiveness of real-time visual feedback in repositioning of
      patients to prevent the formation of new HAPUs.

PMID- 24585162
TI  - Factors influencing critical care nurses' adoption of the AACN practice alert on
      verification of feeding tube placement.
AB  - BACKGROUND: Clinical practice guidelines are intended to bridge the research
      practice gap, yet little is known about how critical care nurses adopt
      guidelines. Feeding tube verification practices remain variable and have led to
      patient harm and death. OBJECTIVES: To examine factors influencing critical care
      nurses' adoption of the American Association of Critical-Care Nurses (AACN)
      practice alert on verification of feeding tube placement and its 4 recommended
      clinical practices. METHODS: Critical care nurses were invited to participate in
      a national, online questionnaire, guided by Rogers' diffusion of innovation
      framework. Descriptive statistics and logistic regression were used for data
      analysis. Alpha level was set at 0.05. RESULTS: Fifty-five percent of the 370
      participating nurses were aware of the practice alert, and 45% had adopted it in
      practice. Only 29% of the adopters had also implemented all 4 clinical practices.
      Significant predictors of adoption included BSN or higher nursing education and
      guideline characteristics of observability and trialability. Predictors of
      implementation of the clinical practices included staff nurse/charge nurse role,
      academic medical center, research/web-based information sources, and perception
      of a policy. Policy was the only significant predictor of implementation of all 4
      practices. Adoption of the practice alert was also a predictor for 2 of 4
      clinical practices. CONCLUSIONS: Personal and organizational factors influenced
      implementation of practices associated with an AACN practice alert. Although a
      research-practice gap exists, the practice alert was a significant source of
      information for 2 of the clinical practices.

PMID- 24585163
TI  - Preventing hypokalemia in critically ill patients.
AB  - BACKGROUND: Many therapies used in critical care cause potassium depletion.
      Current practice relies on potassium replacement protocols after a patient
      becomes hypokalemic. Potassium bolus therapy creates risk for patients, is
      costly, and increases nurses' workload. OBJECTIVES: To determine if administering
      potassium preemptively in maintenance intravenous fluid would prevent episodes of
      hypokalemia and reduce the need for potassium boluses. METHODS: Medical records
      of 267 patients with normal potassium and creatinine levels at admission who did
      not receive total parenteral nutrition were reviewed. The 156 patients who met
      the study criteria were categorized by group: those who received potassium via
      maintenance intravenous fluid (treatment; n = 76) and those who did not (control;
      n = 80). The treatment group had potassium chloride or acetate added to
      intravenous fluid delivered at 36 to 72 mmol/d. RESULTS: The 2 groups did not
      differ significantly in age, race, sex, or admitting diagnosis. Type of
      diagnosis, length of stay, and potassium and creatinine levels at admission did
      not affect the number of potassium boluses for either group. The patients given
      maintenance potassium preemptively received significantly fewer (P < .001)
      potassium boluses (0.8) than did the control group (2.73), for a mean savings of
      $231 per patient for the treatment group. CONCLUSIONS: Patients with normal
      potassium and creatinine levels at admission benefitted from a maintenance
      intravenous dose of potassium of 72 to 144 mmol/L per day. Compared with control
      patients, patients receiving this dose avoided detrimental hypokalemic events,
      had fewer invasive procedures and lower costs, and required less nursing care.

PMID- 24585164
TI  - Arterial catheter setup for glucose control in critically ill patients: a
      randomized controlled trial.
AB  - BACKGROUND: Use of an arterial catheter to obtain hourly blood samples for
      intensive insulin therapy monitoring avoids causing patients the discomfort of
      repeated fingersticks. Returning the clearing volume may decrease procedure
      related blood loss by 50% and minimize the risk of anemia. OBJECTIVES: To compare
      the feasibility of 2 arterial catheter clearing-volume return setups for hourly
      blood extractions and to evaluate the related complications and the accuracy of
      arterial samples in determining glycemia. METHODS: In an open clinical trial, 90
      critical patients undergoing intensive insulin therapy who had a radial arterial
      catheter were randomized to an intervention group-nonwaste needleless setup or
      nonwaste syringe setup and compared with the standard setup (control group).
      Mechanical and infectious complications related to the arterial catheter were
      evaluated. Blood glucose measurements at point-of-care glucometer (arterial
      catheter or fingerstick sample) were compared with laboratory results (venous
      blood). RESULTS: No patient had catheter-related infection in the intervention
      group (an estimated 12776 manipulations); the control group had 2 infection
      episodes in 5230 catheter-days (an estimated 13 075 manipulations). The incidence
      of bacterial colonization was not significantly higher in the needleless group
      than in the syringe group (22.2% vs 12.2%; relative risk, 0.55; 95% CI, 0.16
      1.71), with 1778 (SD, 114) and 1918 (SD, 82) catheter manipulations,
      respectively. Arterial catheter complications were negligible in all patients.
      Glycemia was detected from arterial catheter samples as effectively as with
      laboratory results (venous samples) except when hematocrit was less than 25%.
      CONCLUSIONS: Use of blood obtained via an arterial catheter is safe and effective
      for glucose monitoring in patients undergoing intensive insulin therapy, with no
      increase in complications of catheterization.

PMID- 24585166
TI  - Arm circumference, shape, and length: how interplaying variables affect blood
      pressure measurement in obese persons.

PMID- 24585165
TI  - Patient predictors of dexmedetomidine effectiveness for sedation in intensive
      care units.
AB  - BACKGROUND: Dexmedetomidine, a selective alpha2-adrenergic receptor agonist, is
      increasingly used as a sedative in intensive care despite variations in patients'
      responses. OBJECTIVES: To determine the effectiveness of dexmedetomidine as a
      sedative and specific patient characteristics that play a role in adequate
      sedation with dexmedetomidine. METHODS: A 6-month, pilot, prospective
      observational study was performed in a medical intensive care unit at an academic
      medical center. Patients receiving dexmedetomidine were followed up until use of
      the drug was stopped and they were classified as nonresponders or responders.
      Effective sedation was defined as a score of 3 to 4 on the Sedation Agitation
      Scale after the administration of dexmedetomidine. Patient characteristics,
      laboratory values, home and inpatient medications, and dexmedetomidine dosing
      information were collected to identify predictors of clinical response. RESULTS:
      During the 6-month study period, 38 patients received dexmedetomidine. The drug
      was ineffective as a sedative in 19 patients (50%) and effective in 11 (29%).
      Effectiveness could not be assessed in 8 patients because of clinical
      confounders. According to standard multiple logistic regression analysis,
      successful sedation was more likely in patients with a lower score on the Acute
      Physiology and Chronic Health Evaluation II (Odds Ratio [OR] 0.81; 95% CI, -0.39
      to -0.03) and patients who took antidepressants at home (OR 10.27; 95% CI, 0.23
      to 4.43) than in patients who had a higher score or did not take antidepressants
      at home. CONCLUSIONS: Effective sedation with dexmedetomidine is variable.

PMID- 24585167
TI  - Holiday heart syndrome.

PMID- 24585168
TI  - Lemierre syndrome: not so forgotten!
AB  - Lemierre syndrome is a rare and life-threatening illness. Often referred to as
      "the forgotten disease," its incidence is reported to be as low as 1 in a
      million. The microorganism responsible for Lemierre syndrome is typically
      Fusobacterium necrophorum. The bacterium starts in the pharynx and peritonsillar
      tissue, then disseminates through lymphatic vessels. Severe sepsis rapidly
      develops, as does the hallmark of this syndrome: septic thrombophlebitis of the
      internal jugular vein. This report describes a case of Lemierre syndrome in a
      previously healthy 26-year-old man with life-threatening internal jugular vein
      thrombophlebitis following 2 weeks of an indolent course of pharyngitis. The
      patient's initial presentation and extensive travel history as an Army veteran
      were particularly challenging aspects in establishing his diagnosis. The
      diagnosis of Lemierre syndrome is frequently delayed. Routine use of bedside
      ultrasonography may aid in rapid diagnosis of the disease. 

PMID- 24585169
TI  - Laparoscopic surgical box model training for surgical trainees with limited prior
      laparoscopic experience.
AB  - BACKGROUND: Surgical training has traditionally been one of apprenticeship, where
      the surgical trainee learns to perform surgery under the supervision of a trained
      surgeon. This is time consuming, costly, and of variable effectiveness. Training
      using a box model physical simulator is an option to supplement standard
      training. However, the value of this modality on trainees with limited prior
      laparoscopic experience is unknown. OBJECTIVES: To compare the benefits and harms
      of box model training for surgical trainees with limited prior laparoscopic
      experience versus standard surgical training or supplementary animal model
      training. SEARCH METHODS: We searched the Cochrane Central Register of Controlled
      Trials (CENTRAL), MEDLINE, EMBASE, and Science Citation Index Expanded to May
      2013. SELECTION CRITERIA: We planned to include all randomised clinical trials
      comparing box model trainers versus other forms of training including standard
      laparoscopic training and supplementary animal model training in surgical
      trainees with limited prior laparoscopic experience. We also planned to include
      trials comparing different methods of box model training. DATA COLLECTION AND
      ANALYSIS: Two authors independently identified trials and collected data. We
      analysed the data with both the fixed-effect and the random-effects models using
      Review Manager 5. For each outcome, we calculated the risk ratio (RR), mean
      difference (MD), or standardised mean difference (SMD) with 95% confidence
      intervals (CI) based on intention-to-treat analysis whenever possible. MAIN
      RESULTS: We identified eight trials that met the inclusion criteria. One trial
      including 17 surgical trainees did not contribute to the meta-analysis. We
      included seven trials (249 surgical trainees belonging to various postgraduate
      years ranging from year one to four) in which the participants were randomised to
      supplementary box model training (122 trainees) versus standard training (127
      trainees). Only one trial (50 trainees) was at low risk of bias. The box trainers
      used in all the seven trials were video trainers. Six trials were conducted in
      USA and one trial in Canada. The surgeries in which the final assessments were
      made included laparoscopic total extraperitoneal hernia repairs, laparoscopic
      cholecystectomy, laparoscopic tubal ligation, laparoscopic partial salpingectomy,
      and laparoscopic bilateral mid-segment salpingectomy. The final assessments were
      made on a single operative procedure.There were no deaths in three trials (0/82
      (0%) supplementary box model training versus 0/86 (0%) standard training; RR not
      estimable; very low quality evidence). The other trials did not report mortality.
      The estimated effect on serious adverse events was compatible with benefit and
      harm (three trials; 168 patients; 0/82 (0%) supplementary box model training
      versus 1/86 (1.1%) standard training; RR 0.36; 95% CI 0.02 to 8.43; very low
      quality evidence). None of the trials reported patient quality of life. The
      operating time was significantly shorter in the supplementary box model training
      group versus the standard training group (1 trial; 50 patients; MD -6.50 minutes;
      95% CI -10.85 to -2.15). The proportion of patients who were discharged as day
      surgery was significantly higher in the supplementary box model training group
      versus the standard training group (1 trial; 50 patients; 24/24 (100%)
      supplementary box model training versus 15/26 (57.7%) standard training; RR 1.71;
      95% CI 1.23 to 2.37). None of the trials reported trainee satisfaction. The
      operating performance was significantly better in the supplementary box model
      training group versus the standard training group (seven trials; 249 trainees;
      SMD 0.84; 95% CI 0.57 to 1.10).None of the trials compared box model training
      versus animal model training or versus different methods of box model training.
      AUTHORS' CONCLUSIONS: There is insufficient evidence to determine whether
      laparoscopic box model training reduces mortality or morbidity. There is very low
      quality evidence that it improves technical skills compared with standard
      surgical training in trainees with limited previous laparoscopic experience. It
      may also decrease operating time and increase the proportion of patients who were
      discharged as day-surgery in the first total extraperitoneal hernia repair after
      box model training. However, the duration of the benefit of box model training is
      unknown. Further well-designed trials of low risk of bias and random errors are
      necessary. Such trials should assess the long-term impact of box model training
      on clinical outcomes and compare box training with other forms of training.

PMID- 24585179
TI  - Relationships between mental health distress and work-related factors among
      prefectural public servants two months after the Great East Japan Earthquake.
AB  - BACKGROUND: In times of disaster, public servants face multiple burdens as they
      engage in a demanding and stressful disaster-response work while managing their
      own needs caused by the disaster. PURPOSE: We investigated the effects of work
      related factors on the mental health of prefectural public servants working in
      the area devastated by the Great East Japan Earthquake to identify some ideas for
      organizational work modifications to protect their mental health. METHODS: Two
      months after the earthquake, Miyagi prefecture conducted a self-administered
      health survey of prefectural public servants and obtained 4,331 (82.8%) valid
      responses. We investigated relationships between mental health distress (defined
      as K6 >= 13) and work-related variables (i.e., job type, overwork, and working
      environment) stratified by level of earthquake damage experienced. RESULTS: The
      proportion of participants with mental health distress was 3.0% in the group that
      experienced less damage and 5.9% in the group that experienced severe damage. In
      the group that experienced less damage, working >100 h of overtime per month
      (adjusted odds ratio [OR], 2.06; 95% confidence interval [CI], 1.11-3.82) and
      poor workplace communication (adjusted OR, 10.96; 95% CI, 6.63-18.09) increased
      the risk of mental health distress. In the group that experienced severe damage,
      handling residents' complaints (adjusted OR, 4.79; 95% CI, 1.55-14.82) and poor
      workplace communication (adjusted OR, 9.14; 95% CI, 3.34-24.97) increased the
      risk, whereas involvement in disaster-related work (adjusted OR, 0.39; 95% CI,
      0.18-0.86) decreased the risk. CONCLUSIONS: Workers who have experienced less
      disaster-related damage might benefit from working fewer overtime hours, and
      those who have experienced severe damage might benefit from avoiding contact with
      residents and engaging in disaster-related work. Facilitating workplace
      communication appeared important for both groups of workers.

PMID- 24585180
TI  - Behavioral medicine and prevention of non-communicable diseases in China: current
      challenges and future directions.
AB  - PURPOSE: We describe the emergence of recent public health challenges in China,
      particularly those regarding lifestyle-related non-communicable diseases (NCDs).
      We also summarize some recent examples of behavioral medicine research and
      practice in relation to the prevention and control of NCDs in China. Finally, we
      describe recent changes in the public health system in China and how behavioral
      medicine research and practice can be incorporated into this system to address
      these public health challenges. METHODS: We considered research and policy
      literature from both China and Western countries in order to evaluate the
      relevance of the field of behavioral medicine for addressing the rising NCDs in
      China. RESULTS: Rapid economic development and related social and environmental
      changes have brought about increasing wealth and lifestyle changes in China,
      along with new public health challenges related to the prevention and control of
      NCDs. The field of behavioral medicine has much to offer China in addressing
      these public health challenges. Although behavioral medicine research and
      practice are still at an early stage in China, there are encouraging signs of its
      development, particularly resulting from international collaborations with
      researchers from Western countries. The next stage of this field's development in
      China will involve increased integration of behavioral medicine into public
      health education, training, and the health system. However, this process of
      integration will need to build on China's traditional approaches to public health
      training, research, and practice. CONCLUSIONS: Although the field of behavioral
      medicine in public health is still in its infancy in China, we argue that the
      practice and principles of behavioral medicine are important for successfully
      addressing the substantial burden of NCDs now and in the future.

PMID- 24585181
TI  - Daily positive affect and nocturnal cardiac activation.
AB  - BACKGROUND: Positive affect (PA) has been suggested to benefit health via
      psychobiological pathways. Studies found higher cardiac vagal tone in individuals
      who exhibit a positive emotional style. PURPOSE: This study aimed to examine the
      relationship between momentary-assessed PA and nocturnal heart rate (HR) and
      heart rate variability (HRV) in everyday life. METHODS: Participants were 60
      healthy adults who provided multiple ratings of activated (e.g., dynamic,
      activated) and deactivated PA (e.g., relaxed, even-tempered) and negative affect
      (NA) throughout one day. HR and HRV were recorded the subsequent night. RESULTS:
      Aggregated deactivated PA throughout the day was associated with higher nocturnal
      HRV and lower HR. Activated PA and NA were unrelated with both cardiac variables.
      Findings were independent of other demographic and behavioral confounds.
      CONCLUSIONS: Feeling relaxed, calm, content, and even-tempered throughout the day
      might have beneficial effects on the heart during sleep, although the causality
      of this effect remains speculative because of the correlational design of this
      study.

PMID- 24585182
TI  - Patients' perceptions and experiences of familial hypercholesterolemia, cascade
      genetic screening and treatment.
AB  - BACKGROUND: Familial hypercholesterolemia (FH) is a serious genetic disorder
      affecting approximately 1 in every 300 to 500 individuals and is characterised by
      excessively high low-density lipoprotein (LDL) cholesterol levels, substantially
      increased risk of early-onset coronary heart disease (CHD) and premature
      mortality. If FH is untreated, it leads to a greater than 50 % risk of CHD in men
      by the age of 50 and at least 30 % in women by the age of 60. FH can be diagnosed
      through genetic screening and effectively managed through pharmacological
      treatment and lifestyle changes. PURPOSE: Familial hypercholesterolemia (FH) is a
      genetic health condition that increases the risk of cardiovascular disease.
      Although FH can be effectively managed with appropriate pharmacological and
      dietary interventions, FH detection rate through genetic screening remains low.
      The present study explored perceptions and experiences of FH patients (N = 18)
      involved in a genetic cascade screening programme. METHODS: Face-to-face
      interviews were conducted to assess patients' knowledge and understanding of FH,
      explore factors linked to adherence to health-protective behaviours and examine
      perceptions of genetic screening. RESULTS: Thematic analysis of interviews
      revealed four themes: disease knowledge, severity of FH, lifestyle behavioural
      change and barriers to cascade screening and treatment. Participants recognised
      FH as a permanent, genetic condition that increased their risk of CHD and
      premature mortality. Many participants dismissed the seriousness of FH and the
      importance of lifestyle changes because they perceived it to be effectively
      managed through medication. Despite positive attitudes toward screening, many
      participants reported that relatives were reluctant to attend screening due to
      their relatives' 'fatalistic' outlook or low motivation. Participants believed
      that they had insufficient authority or control to persuade family members to
      attend screening and welcomed greater hospital assistance for contact with
      relatives. CONCLUSIONS: Findings support the adoption of direct methods of
      recruitment to cascade screening led by medical professionals, who were perceived
      as having greater authority. Other implications included the need for clinicians
      to provide clear information, particularly to those who are asymptomatic, related
      to the seriousness of FH and the necessity for adherence to medication and
      lifestyle changes.

PMID- 24585183
TI  - Downregulation of the tumor suppressor HSPB7, involved in the p53 pathway, in
      renal cell carcinoma by hypermethylation.
AB  - In order to identify genes involved in renal carcinogenesis, we analyzed the
      expression profile of renal cell carcinomas (RCCs) using microarrays consisting
      of 27,648 cDNA or ESTs, and found a small heat shock protein, HSPB7, to be
      significantly and commonly downregulated in RCC. Subsequent quantitative PCR
      (qPCR) and immunohistochemical (IHC) analyses confirmed the downregulation of
      HSPB7 in RCC tissues and cancer cell lines in both transcriptional and protein
      levels. Bisulfite sequencing of a genomic region of HSPB7 detected DNA
      hypermethylation of some segments of HSPB7 in RCC cells and concordantly 5-aza-2'
      deoxycytidine (5-Aza-dC) treatment of cancer cells restored HSPB7 expression
      significantly. Ectopic introduction of HSPB7 in five RCC cell lines remarkably
      suppressed cancer cell growth. Interestingly, we found that HSPB7 expression
      could be induced by p53 in a dose-dependent manner, indicating that this gene
      functions in the p53 pathway. Our results imply that HSBP7 is likely to be a
      tumor suppressor gene regulated by p53 and its downregulation by hypermethylation
      may play a critical role in renal carcinogenesis. 

PMID- 24585184
TI  - Psychometric properties of the French Female Sexual Function Index (FSFI).
AB  - INTRODUCTION: Few validated questionnaires are available in French to assess
      sexual function. The aim of this study was thus to validate a French version of
      the Female Sexual Function Index (FSFI) in a sample of French women. METHODS: In
      this prospective monocentric and cross-sectional study, an already existing
      French version of the FSFI, was back-translated and compared to the original
      version. It was then randomly distributed to 800 women attending Gynecology
      consultation at Nantes University Hospital in April 2012. Various statistical
      analyzes were used to test the psychometric properties of the French FSFI.
      RESULTS: 512 questionnaires were completed. Mean FSFI summary score was 25.2.
      Intraclass correlation coefficients were superior to 0.75 and Cronbach's
      coefficients superior to 0.8 similarly to the original version. Variance analysis
      revealed significant differences in summary score between premenopausal and
      postmenopausal women and according to the marital status. Convergent validity was
      excellent (100%) and discriminant validity was satisfactory (89.5%). The
      factorial structure corresponded to the original version with six retrieved
      dimensions. CONCLUSIONS: Our study demonstrated similar or adequate psychometric
      properties of the French version of the FSFI compared to the original English
      version.

PMID- 24585185
TI  - Enacted and internalized stigma and quality of life among people with HIV: the
      role of group identity.
AB  - PURPOSE: This study analyzes the mediating role of social identity in the
      relationship between enacted stigma and internalized stigma and quality of life
      of people with HIV. METHODS: A total of 557 people with HIV participated in this
      study. Participants were recruited from hospitals and non-governmental
      organizations. Questionnaires measuring perceived stigma (Berger's HIV Stigma
      Scale), social identity (Cameron's three factor identity scale), and quality of
      life (Ruiz and Baca's Quality of Life Questionnaire) were administered. The
      instruments were adapted for use with the Spanish population. Structural equation
      modeling (SEM) was used to test the mediation model, and multigroup SEM was
      conducted to evaluate its invariance. RESULTS: Both enacted stigma and
      internalized stigma had a negative influence on the quality of life of people
      with HIV, but this influence occurred in different ways. Enacted stigma had a
      direct negative influence on quality of life. No dimension of group identity
      protected people with HIV from its negative influence. However, the negative
      influence of internalized stigma was totally mediated by some dimensions of group
      identification, mainly through in-group affect. CONCLUSIONS: Group identification
      not only did not protect people with HIV from the negative effects of
      stigmatization, but it may even be detrimental in the case of internalized
      stigma. This suggests that in highly stigmatized groups, the salience of identity
      is negative and worsens the members' opinion of their own group. This argues for
      different kinds of intervention to improve the quality of life of people with
      HIV.

PMID- 24585186
TI  - The voice of American botanists: the founding and establishment of the American
      Journal of Botany, "American botany," and the Great War (1906-1935).
AB  - This paper examines the crucial early history of the American Journal of Botany
      from the years following the founding of the Botanical Society of America in 1906
      to the termination of the agreement for publication with the Brooklyn Botanic
      Garden in 1935. It examines the efforts of individuals like F. C. Newcombe, who
      did the most to raise support for the journal and became the first Editor-in
      Chief, in the context of the growing numbers of professional botanists and plant
      scientists who were actively engaged in research requiring appropriate
      publication venues and in the process of forming an independent identity as
      "American botanists." It also examines the launching of the journal in the
      context of the Great War in Europe and the transition from German botany to
      American botany in the second decade of the 20th century. 

PMID- 24585187
TI  - Enhanced accumulation of fatty acids and triacylglycerols in transgenic tobacco
      stems for enhanced bioenergy production.
AB  - KEY MESSAGE: We report a novel approach for enhanced accumulation of fatty acids
      and triacylglycerols for utilization as biodiesel in transgenic tobacco stems
      through xylem-specific expression of Arabidopsis DGAT1 and LEC2 genes. The use of
      plant biomass for production of bioethanol and biodiesel has an enormous
      potential to revolutionize the global bioenergy outlook. Several studies have
      recently been initiated to genetically engineer oil production in seeds of crop
      plants to improve biodiesel production. However, the "food versus fuel" issues
      have also sparked some studies for enhanced accumulation of oils in vegetative
      tissues like leaves. But in the case of bioenergy crops, use of woody stems is
      more practical than leaves. Here, we report the enhanced accumulation of fatty
      acids (FAs) and triacylglycerols (TAGs) in stems of transgenic tobacco plants
      expressing Arabidopsis diacylglycerol acyltransferase 1 (DGAT1) and leafy
      cotyledon2 (LEC2) genes under a developing xylem-specific cellulose synthase
      promoter from aspen trees. The transgenic tobacco plants accumulated
      significantly higher amounts of FAs in their stems. On an average, DGAT1 and LEC2
      overexpression showed a 63 and 80% increase in total FA production in mature
      stems of transgenic plants over that of controls, respectively. In addition,
      selected DGAT1 and LEC2 overexpression lines showed enhanced levels of TAGs in
      stems with higher accumulation of 16:0, 18:2 and 18:3 TAGs. In LEC2 lines, the
      relative mRNA levels of the downstream genes encoding plastidic proteins involved
      in FA synthesis and accumulation were also elevated. Thus, here, we provide a
      proof of concept for our approach of enhancing total energy yield per plant
      through accumulation of higher levels of FAs in transgenic stems for biodiesel
      production.

PMID- 24585189
TI  - The evolution of mammalian hibernation: lessons from comparative acid-base
      physiology.
AB  - The conquest of land has endowed air-breathers with the capability to utilize
      ventilation not only to acquire oxygen but also to control blood and
      intracellular acid-base state. Hypercapnic acidosis (resulting from ventilatory
      control and/or behavioral choice), thus, has become a universal component of
      hypometabolic states in air-breathers, with inhibitory and/or protective roles.
      Here, special emphasis is placed on the understanding of alterations of acid-base
      state associated with changes in temperature. Hypercapnic acidosis in connection
      with hypometabolism has been found in a variety of air-breathing clades, from
      snails to mammals through lungfish, amphibians, and reptiles. The discovery of
      the plesiomorphic character of mammalian hibernation has made the transfer to
      hibernation biology of the experience gained in the application of hypercapnic
      acidosis (the so-called "pH-stat" procedure) relevant to acid-base control in
      clinical artificial hypothermia. This paves the way for mutual benefits from such
      reciprocal exchange of information between hibernation biology and clinical
      applications. 

PMID- 24585188
TI  - The plasma membrane-localised Ca(2+)-ATPase ACA8 plays a role in sucrose
      signalling involved in early seedling development in Arabidopsis.
AB  - KEY MESSAGE: Arabidopsis Ca (2+) -ATPase ACA8 plays a role in sucrose signalling
      during early seedling development by integrating developmental signals with
      carbon source availability. Calcium (Ca(2+)) is an essential signal transduction
      element in eukaryotic organisms. Changes in the levels of intracellular Ca(2+)
      affect multiple developmental processes in plants, including cell division, polar
      growth, and organogenesis. Here, we report that the plasma-membrane-localised
      Arabidopsis Ca(2+)-ATPase ACA8 plays a role in sucrose signalling during early
      seedling development. Disruption of the ACA8 gene elevated the expression of
      genes that encode transporters for Ca(2+) efflux. The seedlings that carried a T
      DNA insertion mutation in ACA8 experienced water stress during early development.
      This response was unrelated to inadequate osmoregulatory responses and was most
      likely caused by disruption of cell membrane integrity and severe ion leakage. In
      addition, aca8-1 seedlings displayed a significant decline in photosynthetic
      performance and arrested root growth after removal of sucrose from the growth
      medium. The two phenomena resulted from impaired photosynthesis, reduced cell
      proliferation in the root meristem and the sucrose control of cell-cycle events.
      All of the stress-response phenotypes were rescued when expression of ACA8 was
      restored in aca8-1 mutant. Taken together, our results indicate that ACA8
      mediated Ca(2+) signalling contributes to modulate early seedling development and
      coordinates root development with nutrient availability.

PMID- 24585190
TI  - [Laparoscopic total gastrectomy with extended lymphadenectomy and intracorporal
      circular stapled esophagojejunostomy].
AB  - Laparoscopic total gastrectomy for early and advanced gastric cancer is an
      exacting procedure which is increasingly performed in specialised institutions.
      Not only gastric resection and extended lymphadenectomy but especially the
      reconstruction by oesophagojejunostomy is a technically demanding and vulnerable
      operative step. In this article we present our laparoscopic technique of total
      gastrectomy with extended lymphadenectomy and complete intracorporal
      reconstruction by end-to-side circular stapled oesophagojejunostomy. The
      operative technique of the gastric resection, the extended lymphadenectomy and
      the reconstruction are described in detail in a step-by-step approach and
      demonstrated in a supplemental video.

PMID- 24585192
TI  - [Upper GI cancer in the 21st century: rise of endoscopic, minimally invasive and
      multimodal therapeutic strategies].

PMID- 24585191
TI  - [Robotic-assisted minimally invasive abdominothoracal oesophageal resection with
      intrathoracic anastomosis].
AB  - BACKGROUND: Ivor Lewis oesophagectomy is one of the approaches used worldwide for
      treating oesophageal cancer. The adoption of minimally invasive oesophagectomy
      has increased worldwide since its first description more than 15 years ago.
      However, minimally invasive oesophagectomy with a chest anastomosis has
      advantages. By using a four-arm robotic platform, not only the preparation of the
      gastric tube and mobilisation of the oesophagus but also the intrathoracic
      anastomosis of the oesophagogastrostomy can be performed in a comfortable and
      safe way. INDICATION: The indication for oesophageal resection is oesophageal
      cancer. PROCEDURE: The operative procedure comprises robotic-assisted
      abdominothoracal oesophageal resection with reconstruction by a gastric tube and
      intrathoracic anastomosis (Ivor Lewis procedure). CONCLUSION: Robotic abdominal
      and thoracic minimally invasive esophagectomy is feasible, and safe with a
      complete lymph node dissection. Especially the intrathoracic anastomosis of the
      oesophagogastrostomy can be performed in a comfortable and safe way.

PMID- 24585193
TI  - [How radical should the surgical therapy for gastric/cardia cancer be?].
AB  - With the exception of tumours limited to the mucosa, surgical resection of the
      primary tumour and its local lymph node metastases still remains the sole option
      for a curative therapy for potentially resectable gastric cancer, as long as a
      complete tumour resection (R0 resection) can be performed. In this context, the
      extent of surgical radicality has been discussed over the last years, especially
      based on the following aspects: 1. extent of lymphadenectomy/need for
      splenectomy; 2. subtotal versus total gastrectomy; 3. surgical therapy for cardia
      cancer; 4. operative approach in cT4-tumours; 5. laparoscopic versus open
      surgery. Based on the recent study results as well as the current guidelines,
      this review will discuss these specific issues and gives an insight about the
      recommended surgical radicality in gastric cancer.

PMID- 24585194
TI  - [Challenges and limits for endoscopic resection of oesophageal and
      oesophagogastric cancer].
AB  - There is good evidence for the safety and efficacy of endoscopic treatment for
      early neoplasia in Barrett's oesophagus and in oesophageal squamous epithelium
      within defined margins, and this form of therapy is therefore the treatment of
      choice. With a low morbidity rate, it offers patients a good quality of life with
      preservation of the organ. The mortality risk is minimal. The decisive element
      for success is early diagnosis. Oesophageal resection and
      radiotherapy/chemotherapy are nowadays reserve procedures in the treatment of
      early oesophageal carcinoma and should only be used in patients in whom the
      tumour shows defined histological risk factors or endoscopic therapy has failed.
      Discussion is currently taking place on whether the criteria used to indicate
      endoscopic therapy for early Barrett's adenocarcinoma can be expanded to include
      lesions with superficial submucosal infiltration and no additional histological
      risk factors.

PMID- 24585195
TI  - [Therapeutic decisions in patients with operable, non-metastatic oesophageal
      cancer].
AB  - BACKGROUND: Therapy for oesophageal carcinoma is a subject of controversial
      debate. The aim of this study is to answer the question how the therapeutic
      decision in patients with operable, non-metastatic oesophageal cancer should be
      made. MATERIALS AND METHODS: A systematic literature research regarding different
      therapeutic strategies in patients with oesophageal cancer was undertaken.
      RESULTS: Multiple criteria influence the therapy for oesophageal carcinoma.
      Radical oesophagectomy in a multimodal setting is the therapy of choice.
      Definitive chemoradiation is a conservative option for high risk patients.
      CONCLUSION: Therapeutic decisions in patients with oesophageal cancer should only
      be made after standardised staging and accurate risk analysis.

PMID- 24585196
TI  - [Scope and limitations of minimally invasive resections of the oesophagus and
      stomach].
AB  - BACKGROUND: Although minimally invasive surgery is being increasingly performed
      for the treatment of upper gastrointestinal cancers, the discussion on potential
      advantages and oncological accuracy is still controversial. MATERIAL AND METHODS:
      In the framework of a literature survey, current trials on minimally invasive
      oesophageal resection and laparoscopic abdominal surgery have been analysed.
      RESULTS: Minimally invasive oesophagectomy and laparoscopic gastric resections
      for cancer are safe. Minimally invasive resections result in an improved short
      term outcome postoperatively in view of less pain, less blood loss and shorter
      duration of hospital stay. While mortality is equal, morbidity following
      minimally invasive surgery is reduced. Especially pulmonary complications
      decrease on the application of minimally invasive oesophagectomy. Minimally
      invasive operations last longer than open procedures. The oncological results
      seem to be equal between open and minimally invasive operations. A few studies
      have shown that laparoscopic gastric resections may result in a reduced number of
      lymph nodes harvested. The long-term survival between open and laparoscopic
      resections did not differ in any study. CONCLUSION: Minimally invasive resections
      for oesophageal and gastric cancer are safe and show several advantages in short
      term outcome. Oncological long-term results seem to be comparable. The potential
      risk of a reduced number of harvested lymph nodes during laparoscopic gastrectomy
      has to be addressed by an adequate surgical technique.

PMID- 24585197
TI  - [3rd Trinational Congress of German-Speaking Thoracic Surgeons].

PMID- 24585198
TI  - [Video-assisted thoracoscopic (VATS) sublobar anatomic resections for lung
      cancer].
AB  - Pulmonary segmentectomy implies the removal of one or more anatomic units of the
      lung. It requires dissection of the segmental bronchus and artery and
      identification of the intersegmental vein, which should be respected. Benign
      lesions, solitary pulmonary nodules, pulmonary adenocarcinoma in situ and T1a
      lung cancer are possible indications. The VATS approach for segmentectomies is
      technically challenging and differs slightly from the conventional open one. Its
      combination of minimal invasiveness with a maximum of lung parenchyma
      preservation provides a surgical treatment option for NSCLC patients with little
      pulmonary reserve. Data on the oncologic outcome after VATS segmentectomy are
      inconclusive as yet.

PMID- 24585199
TI  - What is the clinical value of PET/CT in the diagnosis of pulmonary nodules?
AB  - The noninvasive diagnostic workup of solitary pulmonary nodules (SPNs) continues
      to be a challenge for radiologists and nuclear medicine physicians. Morphological
      evaluation is useful to differentiate between benign and malignant SPNs, but
      there is a considerable overlap between the benign and the malignant features,
      resulting in a large fraction of morphologically indeterminate SPNs. Integrated
      PET/CT with the glucose analogue 18F-fluorodeoxyglucose (FDG PET/CT) can
      simultaneously evaluate morphological characteristics, anatomic location and
      metabolic status of SPNs. FDG PET/CT has been shown to result in an overall
      improved accuracy for the detection of malignant SPNs. In addition, it is the
      most accurate technique for the staging of malignant SPNs. On the other hand,
      there are many causes for false positive or false negative FDG PET/CTs.
      Therefore, FDG PET/CT cannot replace histological evaluation of SPNs, but can be
      clinically helpful in specific subgroups of patients with SPNs. The goal of this
      review is to provide an overview of the literature on PET/CT imaging in SPNs and
      to describe several clinical scenarios for the use of FDG PET/CT in SPNs.

PMID- 24585201
TI  - [Thymectomy in myasthenia and/or thymoma].
AB  - Thymectomy, the surgical removal of the thymic gland, is essential in cases of
      thymoma. The majority of cases of a myasthenia gravis (MG) represent a relative
      indication for thymectomy which requires cooperation with specialized
      neurologists. Patients with MG may present with a tumor of the thymic gland. In
      case of suspicious thymoma, the resectability of the tumor has to be evaluated in
      the preoperative diagnostic. The clinical condition of patients with MG has to be
      stabilized preoperatively. The aim of thymectomy is the radical removal of
      thymoma and/or maximal improvement of MG symptoms. This requires the complete
      extirpation of the thymic gland including all ectopic thymic tissue in the
      anterior mediastinum. There is a variety of surgical techniques for performing a
      complete thymectomy. In addition to the conventional techniques with sternotomy,
      the significance of minimally-invasive approaches is increasing rapidly. Despite
      the ongoing scarcity of data of higher evidence concerning the procedure of
      thymectomy an increasing number of equivalent results with minimally-invasive
      operation techniques for MG and for thymoma are available. The successful
      surgical performance of a thymectomy is part of an interdisciplinary cooperation
      in the perioperative treatment of MG as well as the postoperative long-term care
      for patients with MG and/or thymoma.

PMID- 24585203
TI  - Keep your heart in shape: molecular chaperone networks for treating heart
      disease.
AB  - Despite major advances in the treatment of cardiac diseases, there is still a
      great need for drugs capable of counteracting the deterioration of cardiac muscle
      function in congestive heart failure. The role of misfolded protein accumulation
      as a causal event in the physiopathology of common cardiac diseases is an
      important emerging concept. Indeed, diverse stress conditions, including
      mechanical stretching and oxidative stress, can induce misfolded protein
      accumulation, causing cardiomyocyte death. Cells react to these stress conditions
      by activating molecular chaperones, a class of proteins that represents an
      endogenous salvage machinery, essential for rescuing physiological cell functions
      and sustaining cell survival. Chaperones, also known as heat shock proteins
      (Hsps), prevent accumulation of damaged proteins by promoting either their
      refolding or degradation via the proteasome or the autophagosome systems. In
      addition, molecular chaperones play a key role in intracellular signalling by
      controlling conformational changes required for activation/deactivation of
      signalling proteins, and their assembly in specific signalosome complexes. The
      key role of molecular chaperones in heart function is highlighted by the fact
      that a number of genetic mutations in chaperone proteins result in different
      forms of cardiomyopathies. Moreover, a considerable amount of experimental
      evidence indicates that increasing expression of chaperone proteins leads to an
      important cardio-protective role in ischaemia/reperfusion injury, heart failure,
      and arrhythmia, implicating these molecules as potential innovative therapeutic
      agents. 

PMID- 24585202
TI  - Canagliflozin, a sodium glucose co-transporter 2 inhibitor, improves model-based
      indices of beta cell function in patients with type 2 diabetes.
AB  - AIMS/HYPOTHESIS: In rodent models of diabetes, treatment with sodium glucose co
      transporter 2 (SGLT2) inhibitors improves beta cell function. This analysis
      assessed the effects of the SGLT2 inhibitor, canagliflozin, on model-based
      measures of beta cell function in patients with type 2 diabetes. METHODS: Data
      from three Phase 3 studies were analysed, in which: (Study 1) canagliflozin 100
      and 300 mg were compared with placebo as monotherapy for 26 weeks; (Study 2)
      canagliflozin 100 and 300 mg were compared with placebo as add-on to metformin +
      sulfonylurea for 26 weeks; or (Study 3) canagliflozin 300 mg was compared with
      sitagliptin 100 mg as add-on to metformin + sulfonylurea for 52 weeks. In each
      study, a subset of patients was given mixed-meal tolerance tests at baseline and
      study endpoint, and model-based beta cell function parameters were calculated
      from plasma glucose and C-peptide. RESULTS: In Studies 1 and 2, both
      canagliflozin doses increased beta cell glucose sensitivity compared with
      placebo. Placebo-subtracted least squares mean (LSM) (SEM) changes were 23 (9)
      and 18 (9) pmol min(-1) m(-2) (mmol/l)(-1) with canagliflozin 100 and 300 mg,
      respectively (p < 0.002, Study 1), and 16 (8) and 10 (9) pmol min(-1) m(-2)
      (mmol/l)(-1) (p < 0.02, Study 2). In Study 3, beta cell glucose sensitivity was
      minimally affected, but the insulin secretion rate at 9 mmol/l glucose increased
      to similar degrees from baseline with canagliflozin and sitagliptin [LSM (SEM)
      changes 38 (8) and 28 (9) pmol min(-1) m(-2), respectively; p < 0.05 for both].
      CONCLUSIONS/INTERPRETATION: Treatment with canagliflozin for 6 to 12 months
      improved model-based measures of beta cell function in three separate Phase 3
      studies. TRIAL REGISTRATION: Clinicaltrials.gov NCT01081834 (Study 1);
      NCT01106625 (Study 2); NCT01137812 (Study 3).

PMID- 24585204
TI  - Replacing a suite of commercial pectinases with a single enzyme, pectate lyase B,
      in Saccharomyces cerevisiae fermentations of cull peaches.
AB  - Fermentation of pectin-rich biomass with low concentrations of polysaccharides
      requires some treatment of the pectin, but does not need complete degradation of
      the polysaccharide to reach maximum ethanol yields. Cull peaches, whole rotten
      fruits that are not suitable for sale, contain high concentrations of glucose
      (27.7% dw) and fructose (29.3% dw) and low amounts of cellulose (2.8% dw),
      hemicellulose (4.5% dw) and pectin (5.6% dw). Amounts of commercial
      saccharification enzymes, cellulase and cellobiase can be significantly decreased
      and commercial pectinase mixtures can be replaced completely with a single
      enzyme, pectate lyase (PelB), while maintaining ethanol yields above 90% of the
      theoretical maximum. PelB does not completely degrade pectin; it only releases
      short chain oligogalacturonides. However, the activity of PelB is sufficient for
      the fermentation process, and its addition to fermentations without commercial
      pectinase increases ethanol production by ~12%.

PMID- 24585205
TI  - Advance statements for borderline personality disorder: a qualitative study of
      future crisis treatment preferences.
AB  - OBJECTIVE: Little is known about the crisis treatment preferences of people with
      borderline personality disorder. Clinicians may also question service users'
      ability to make considered decisions about their treatment when in crisis.
      Therefore, this qualitative study aimed to investigate crisis treatment
      preferences of a sample of community-dwelling adults with borderline personality
      disorder. METHODS: Participants were 41 adults with borderline personality
      disorder who had created joint crisis plans during a randomized controlled trial.
      Data from all 41 joint crisis plans were analyzed iteratively via a thematic
      analysis framework. RESULTS: Participants gave clear statements in their crisis
      plans relating to the desire to recover from the crisis and to improve their
      social functioning. Key themes included the desire to be treated with dignity and
      respect and to receive emotional and practical support from clinicians. Many
      participants spoke of the importance of connecting with others during periods of
      crisis, but several reported a clear desire to be left alone during a future
      crisis. Other themes concerned preferences for specific treatment refusals during
      crises, including particular types of psychotropic medication and involuntary
      treatment. CONCLUSIONS: The variation of participants' preferences underscores
      the importance of developing individually tailored crisis plans for people with
      borderline personality disorder. The need to be treated with dignity and respect
      and to be given autonomy in decision making--also identified in global surveys of
      people with severe mental illness--is important to people with borderline
      personality disorder. Key messages for clinicians, service users, and policy
      makers, in addition to staff training issues, are discussed.

PMID- 24585206
TI  - Theory, synthesis and reactivity of quintuple bonded complexes.
AB  - This perspective reviews recent advances in the newly discovered metal-to-metal
      quintuple bonded complexes. The idea of the structures of the metal-metal
      quintuple bonded complexes was initiated by theoreticians in 1979 and 2001 based
      on two types of model compounds, the D3h M2L6 and trans-bent M2H2, respectively.
      This theoretical hypothesis was put into practice in 2005 with the preparation of
      the first isolable quintuple bonded chromium terphenyl dimer Cr2Ar'2 (Ar' = 2,6
      (2,6-i-Pr2C6H3)2C6H3). After this landmark discovery, many N-based donor
      stabilized dinuclear group 6 quintuple bonded complexes with very short metal
      metal separations have been identified by X-ray crystallography, and their
      quintuple bonding was corroborated by magnetic measurements and theoretical
      calculations. Unlike the quadruple bonded bimetallic units uniformly supported in
      a tetragonal environment, the configuration of the characterized quintuple bonded
      dinuclear complexes varies with the ligands and metals. Three types of quintuple
      bonded complexes have been identified to date. In addition to their geometry
      variation and interesting bonding schemes, these low-valent and low-coordinate
      quintuple bonded complexes are highly reducing and have been shown to be reactive
      towards small inorganic molecules and unsaturated organics. 

PMID- 24585212
TI  - Expression and functional analysis of genes encoding cytokinin receptor-like
      histidine kinase in maize (Zea mays L.).
AB  - Cytokinin signaling is vital for plant growth and development which function via
      the two-component system (TCS). As one of the key component of TCS, transmembrane
      histidine kinases (HK) are encoded by a small gene family in plants. In this
      study, we focused on expression and functional analysis of cytokinin receptor
      like HK genes (ZmHK) in maize. Firstly, bioinformatics analysis revealed that
      seven cloned ZmHK genes have different expression patterns during maize
      development. Secondly, ectopic expression by CaMV35S promoter in Arabidopsis
      further revealed that functional differentiation exists among these seven
      members. Among them, the ZmHK1a2-OX transgenic line has the lowest germination
      rate in the dark, ZmHK1-OX and ZmHK2a2-OX can delay leaf senescence, and seed
      size of ZmHK1-OX, ZmHK1a2-OX, ZmHK2-OX, ZmHK3b-OX and ZmHK2a2-OX was obviously
      reduced as compared to wild type. Additionally, ZmHK genes play opposite roles in
      shoot and root development; all ZmHK-OX transgenic lines display obvious shorter
      root length and reduced number of lateral roots, but enhanced shoot development
      compared with the wild type. Most notably, Arabidopsis response regulator ARR5
      gene was up-regulated in ZmHK1-OX, ZmHK1a2-OX, ZmHK2-OX, ZmHK3b-OX and ZmHK2a2-OX
      as compared to wild type. Although the causal link between ZmHK genes and
      cytokinin signaling pathway is still an area to be further elucidated, these
      findings reflected that the diversification of ZmHK genes expression patterns and
      functions occurred in the course of maize evolution, indicating that some ZmHK
      genes might play different roles during maize development. 

PMID- 24585213
TI  - Association Between Ambient Levels of Polycyclic Aromatic Hydrocarbons and Small
      for Gestational Age Hispanic Infants Born Along the United States-Mexico Border.
AB  - Few studies have examined associations between polycyclic aromatic hydrocarbons
      (PAHs) and birth outcomes, and no studies have been conducted in El Paso County
      Texas, along the United States-Mexico border. Infants born from 2005-2007 to
      Hispanic mothers with a birth weight less than the 10th percentile for
      gestational age and sex were classified as small for gestational age (SGA). PAH
      exposures were estimated for the entire period of gestation and for each
      trimester of pregnancy using ambient air monitoring data from 2004-2007. Logistic
      regression was used to estimate odds ratios for the association between PAH
      levels and SGA infants. There was marked seasonal variation in the carcinogenic
      PAHs. Established risk factors for SGA were observed to be associated with SGA
      births in this population. No associations were detected between PAH levels and
      SGA births. These findings provide no evidence of an association between PAHs and
      SGA infants. 

PMID- 24585214
TI  - The inhibitory effect of anthocyanins on Akt on invasion and epithelial
      mesenchymal transition is not associated with the anti-EGFR effect of the
      anthocyanins.
AB  - Evidence suggests that anthocyanins inhibit EGFR and Akt activity. However, it is
      still unknown whether the inhibitory effect of anthocyanins on Akt is associated
      with the anti-EGFR effect. The effect of anthocyanins on epithelial-mesenchymal
      transition (EMT) has not been extensively studied. Therefore, we investigated the
      effects of anthocyanins from fruits of Vitis coignetiae Pulliat (AIMs) on EGF
      induced EMT and the underlying molecular mechanisms. AIMs suppressed the invasion
      of A549 cells in a dose-dependent manner. AIMs inhibited the phosphorylation of
      Akt and EGFR, but the inhibitory effect on Akt was not derived from EGFR. EGF re
      induced Akt phosphorylation at Thr308 in the AIM-treated cells, but not Akt
      phosphorylation at Ser473. AIMs also inhibited EMT of cancer cells. AIMs
      inhibited glycogen synthase kinase-3beta phosphorylation and beta-catenin
      expression that are invovled in EMT. We confirmed these findings with
      transforming growth factor (TGF)-beta. In conclusion, these data suggest that the
      inhibitory effect of AIMs on Akt activity is independent of EGFR, and that AIMs
      suppressed invasion and migration at least in part by suppressing EMT by
      inhibiting Akt activity as well as EGFR. This study provides evidence that AIMs
      may have anticancer effects on human cancer cells.

PMID- 24585215
TI  - Hepatitis e virus: current concepts and future perspectives.
AB  - For many years, hepatitis E was considered a disease found only in certain
      developing countries. In these geographical settings, hepatitis E virus (HEV)
      causes a self-limiting hepatitis in young adults, except in pregnant females, in
      whom the mortality is 25 %. Our understanding of HEV has changed radically in the
      past decade. It is now evident that HEV is a threat to global health. This review
      article considers the current concepts and future perspectives of HEV and its
      effects on human health, with particular reference to developed countries. 

PMID- 24585217
TI  - Effect of feeding sorghum straw based complete rations with different roughage to
      concentrate ratio on dry matter intake, nutrient utilization, and nitrogen
      balance in Nellore ram lambs.
AB  - An experiment was conducted by feeding sorghum straw (Sorghum bicolor) based
      complete rations at roughage concentrate ratio 70:30 (CR-I), 60:40 (CR-II), 50:50
      (CR-III), and 40:60 (CR-IV) for 180 days to find out suitable ratio of sorghum
      straw in the complete ration (mash form) on nutrient utilization and nitrogen
      balance in Nellore ram lambs. The DMI (g/day) increased significantly (P < 0.05)
      as level of concentrate increased in complete rations. No significant difference
      was found in digestibilities of proximate nutrients. However, CP digestibility
      was higher either significantly or nonsignificantly by 2.12, 5.50, and 9.36 %,
      respectively, in lambs fed with CR-II (P > 0.05), CR-III (P > 0.05), and CR-IV (P
      < 0.05) rations in comparison to lambs fed with CR-I ration. Furthermore, CP
      digestibility was higher by 7.09 and 3.66 % in lambs fed with CR-IV ration than
      those fed with CR-II (P < 0.05) and CR-III (P > 0.05) ration. The average CWC
      digestibility coefficients were comparable among four rations. The N intake
      (g/day) was significantly (P < 0.01) different and progressively increased by
      31.46, 48.69, and 82.86 % in ram lambs fed with CR-II, CR-III, and CR-IV rations,
      respectively, in comparison to CR-I ration. The N balance (g/day) was higher
      either significantly or nonsignificantly by 34.46 (P > 0.05), 133.46 (P < 0.01),
      and 198.87 % (P < 0.01) with CR-II, CR-III, and CR-IV rations, respectively, in
      comparison to CR-I ration. Based on results, it is inferred that the level of
      sorghum straw in complete ration had no effect on digestibility of nutrients
      barring crude protein in Nellore ram lambs. 

PMID- 24585216
TI  - Next-Generation Sequencing to Help Monitor Patients Infected with HIV: Ready for
      Clinical Use?
AB  - Given the extreme variability of the human immunodeficiency virus (HIV) and its
      ability to replicate as complex viral populations, HIV variants with reduced
      susceptibility to antiretroviral drugs or with specific coreceptor tropism (CCR5
      and/or CXCR4) may be present as minority members of the viral quasispecies. The
      sensitivity of current HIV genotypic or phenotypic assays is limited, and thus,
      these tests usually fail to detect low-abundance viral variants. Next-generation
      (deep) sequencing (NGS) produces an enormous amount of information that allows
      the detection of minority HIV variants at levels unimaginable using standard
      Sanger sequencing. NGS technologies continue to evolve, opening new and more
      affordable opportunities to implement this methodology in clinical laboratories,
      and HIV is not an exception. The ample use of a battery of more effective
      antiretroviral drugs, together with careful patient monitoring based on HIV
      resistance testing, has resulted in HIV-infected patients whose disease is
      usually well-controlled. The vast majority of adherent patients without
      detectable resistance become virologically suppressed; however, a subset of these
      patients with undetectable resistance by standard methods may fail antiretroviral
      therapy, perhaps due to the presence of minority HIV-resistant variants. Novel
      NGS-based HIV assays with increased sensitivity for identifying low-level drug
      resistance and/or coreceptor tropism may play an important role in the success of
      antiretroviral treatments. 

PMID- 24585220
TI  - Kinetics of heterogeneous reactions of ozone with representative PAHs and an
      alkene at the air-ice interface at 258 and 188 K.
AB  - The kinetics of the reaction of an alkene (E-stilbene) and three polycyclic
      aromatic hydrocarbons (perylene, anthracene and fluoranthene), as examples of
      environmental pollutants, with ozone on the surface of ice grains (also called
      "artificial snow"), produced by shock-freezing of aqueous solutions, was studied
      at submonolayer pollutant coverages (c = 1.5 * 10(-8) to 3 * 10(-10) mol kg(-1))
      and two different temperatures (258 and 188 K). This work supports and extends
      our previous discovery of a remarkable increase in the apparent ozonation rates
      with decreasing temperature. The ozonation kinetic results were evaluated using
      the Langmuir-Hinshelwood model and, in one case, the Eley-Rideal kinetic model.
      It is shown that the apparent rate enhancement is related to the specific nature
      of the ice surface at different temperatures, which influences the availability
      of contaminants to gaseous ozone, and to inherent reactivities of the
      contaminants. The maximum pseudofirst-order rate constants and the lifetimes of
      the studied compounds are provided. At a typical atmospheric ozone concentration
      in polar areas (50 ppbv), the lifetimes were estimated to be on the order of
      hours (258 K) or tens of minutes (188 K) for alkenes, and hundreds (258 K) or
      tens (188 K) of days for PAHs, thus approximately of the same magnitude or longer
      than those found for the gas-phase reactions. We imply that this rate enhancement
      at lower temperatures is a general phenomenon, and we provide data to implement
      heterogeneous reactions in snow in models that predict the extent of chemical
      reactions occurring in cold environments. 

PMID- 24585219
TI  - Diagnostic ultrasound features and outcome of restrictive foramen ovale in
      fetuses with structurally normal hearts.
AB  - Intrauterine foramen ovale (FO) restriction in association with congenital heart
      disease (CHD) carries a poor prognosis. However, in the absence of CHD, the
      clinical importance of restrictive FO in the fetus is not well understood. We
      evaluated the antenatal prevalence, clinical presentation, diagnostic ultrasound
      features, and outcome of restrictive FO in fetuses without CHD. We reviewed the
      echocardiographic and clinical records of 23 fetuses diagnosed with a restrictive
      FO and structurally normal heart between 2001 and 2012. The atrial septum,
      dimensions of cardiac structures, left and right cardiac output and Doppler
      interrogation of cardiac flows were examined. The clinical outcomes of all
      fetuses with restrictive FO were analysed. Restrictive FO was identified in 23 of
      1,682 (1.4%) fetuses with no CHD. Enlarged right heart structures (100%),
      hypermobile or redundant primum atrial septum (91%), increased right-to-left
      ventricular cardiac output ratio (91%), and posteriorly angulated ductus
      arteriosus (68%) were the most common echocardiographic findings associated with
      this rare phenomenon. Additional noncardiac systemic abnormalities were
      identified in 13 (56%) babies. Seven (30%) neonates developed persistent
      pulmonary hypertension, and 7 infants died. Antenatal restrictive FO is an
      underrecognised entity despite being a common cause of right heart dilatation in
      the fetus. In the absence of CHD, restrictive FO is well tolerated antenatally,
      but its frequent association with noncardiac abnormalities and pulmonary
      hypertension in the neonate are noteworthy.

PMID- 24585221
TI  - Bronchial thermoplasty for moderate or severe persistent asthma in adults.
AB  - BACKGROUND: Bronchial thermoplasty is a procedure that consists of the delivery
      of controlled radiofrequency-generated heat via a catheter inserted into the
      bronchial tree of the lungs through a flexible bronchoscope. It has been
      suggested that bronchial thermoplasty works by reducing airway smooth muscle,
      thereby reducing the ability of the smooth muscle to bronchoconstrict. This
      treatment could then reduce asthma symptoms and exacerbations, resulting in
      improved asthma control and quality of life. OBJECTIVES: To determine the
      efficacy and safety of bronchial thermoplasty in adults with bronchial asthma.
      SEARCH METHODS: We searched the Cochrane Airways Group Specialised Register of
      Trials (CAGR) up to January 2014. SELECTION CRITERIA: We included randomised
      controlled clinical trials that compared bronchial thermoplasty versus any active
      control in adults with moderate or severe persistent asthma. Our primary outcomes
      were quality of life, asthma exacerbations and adverse events. DATA COLLECTION
      AND ANALYSIS: Two review authors independently extracted data and assessed risk
      of bias. MAIN RESULTS: We included three trials (429 participants) with
      differences regarding their design (two trials compared bronchial thermoplasty vs
      medical management and the other compared bronchial thermoplasty vs a sham
      intervention) and participant characteristics; one of the studies included
      participants with more symptomatic asthma compared with the others.The pooled
      analysis showed improvement in quality of life at 12 months in participants who
      received bronchial thermoplasty that did not reach the threshold for clinical
      significance (3 trials, 429 participants; mean difference (MD) in Asthma Quality
      of Life Questionnaire (AQLQ) scores 0.28, 95% confidence interval (CI) 0.07 to
      0.50; moderate-quality evidence). Measures of symptom control showed no
      significant differences (3 trials, 429 participants; MD in Asthma Control
      Questionnaire (ACQ) scores -0.15, 95% CI -0.40 to 0.10; moderate-quality
      evidence). The risk of bias for these outcomes was high because two of the
      studies did not have a sham intervention for the control group.The results from
      two trials showed a lower rate of exacerbation after 12 months of treatment for
      participants who underwent bronchial thermoplasty. The trial with sham
      intervention showed a significant reduction in the proportion of participants
      visiting the emergency department for respiratory symptoms, from 15.3% on sham
      treatment to 8.4% over 12 months following thermoplasty. The trials showed no
      significant improvement in pulmonary function parameters (with the exception of a
      greater increase in morning peak expiratory flow (PEF) in one trial). Treated
      participants who underwent bronchial thermoplasty had a greater risk of
      hospitalisation for respiratory adverse events during the treatment period (3
      trials, 429 participants; risk ratio 3.50, 95% CI 1.26 to 9.68; high-quality
      evidence), which represents an absolute increase from 2% to 8% (95% CI 3% to 23%)
      over the treatment period. This means that six of 100 participants treated with
      thermoplasty (95% CI 1 to 21) would require an additional hospitalisation over
      the treatment period. No significant difference in the risk of hospitalisation
      was noted at the end of the treatment period.Bronchial thermoplasty was
      associated with an increase in respiratory adverse events, mainly during the
      treatment period. Most of these events were mild or moderate, appeared in the 24
      hour post-treatment period, and were resolved within a week. AUTHORS'
      CONCLUSIONS: Bronchial thermoplasty for patients with moderate to severe asthma
      provides a modest clinical benefit in quality of life and lower rates of asthma
      exacerbation, but no significant difference in asthma control scores. The quality
      of life findings are at risk of bias, as the main benefits were seen in the two
      studies that did not include a sham treatment arm. This procedure increases the
      risk of adverse events during treatment but has a reasonable safety profile after
      completion of the bronchoscopies. The overall quality of evidence regarding this
      procedure is moderate. For clinical practice, it would be advisable to collect
      data from patients systematically in independent clinical registries. Further
      research should provide better understanding of the mechanisms of action of
      bronchial thermoplasty, as well as its effect in different asthma phenotypes or
      in patients with worse lung function.

PMID- 24585222
TI  - Assessment of endodontic treatment of c-shaped root canals.
AB  - This communication presents the treatment of 15 cases of c-shaped canals in
      molars and their treatment outcome with two different obturation methods. The
      data from 901 patients who received root canal treatment in a molar tooth were
      examined regarding c-shaped root canals, their treatment and their status one
      year post op. Among the 901 cases, 15 molars had a c-shaped root canal morphology
      (1,66%). C-shaped canals occurred mainly in second mandibular molars (73,3%). The
      obturation was either performed with gutta-percha and sealer (5 cases) or with
      Mineral Trioxide Aggregate as apical plug (MTA; 10 cases). All cases reached a
      symptomless status clinically and 14 cases showed apical healing in the
      radiographic control.

PMID- 24585229
TI  - Research & services partnerships: lessons learned through a national partnership
      between clinical leaders and researchers.
AB  - This column describes lessons learned by U.S. Department of Veterans Affairs (VA)
      researchers and clinical operations managers while they were engaged in a unique
      partnership. In this partnership, researchers turned generalizable lessons from
      implementation research into actionable guidance for use by clinical managers in
      implementing health care system change. The lessons learned are reflections about
      the necessary foundations for partnering, the importance of relationships, the
      need for regular communication, and the need to recognize and adapt to partners'
      timelines and time constraints.

PMID- 24585231
TI  - Finding the sweet spot in preoperative assessment.

PMID- 24585230
TI  - An observational cohort study to assess glycosylated hemoglobin screening for
      elective surgical patients.
AB  - INTRODUCTION: Uncontrolled blood glucose is associated with a higher incidence of
      surgical site infections, greater utilization of resources, and increased
      mortality. Preoperative screening for diabetes in elective surgical patients is
      not routinely performed. The purpose of this study was to examine blood glucose
      control in a preoperative surgical population. METHODS: Following ethics
      approval, adults presenting to the pre-surgical screening clinic in preparation
      for elective surgery were recruited. Data collection included a self-administered
      questionnaire on diabetic risk factors and blood glucose testing, including
      glycosylated hemoglobin (HbA1c). Descriptive analyses were conducted. RESULTS:
      Seventy of the 402 participants (17.4%) had a previous diagnosis of diabetes
      (diabetics). Among those without a history of diabetes (n = 332 non-diabetics),
      23.2% (n = 77) were considered very high risk for diabetes (HbA1c = 6.0-6.4%),
      and 3.9% (n = 13) had a provisional diagnosis of diabetes (HbA1c >= 6.5%). Fifty
      six percent (n = 39/70) of diabetics had suboptimal glycemic control (HbA1c >
      7.0%), and 51.3% (n = 20/39) of this subgroup presumed their blood sugars were
      reasonably or very well controlled. Fifteen percent (n = 2/13) of patients with a
      provisional diagnosis of diabetes (HbA1c >= 6.5%) had an elevated random blood
      sugar (RBS) (>= 11.1 mmol.L(-1)), while 67% (n = 8/12) had an elevated fasting
      blood sugar (FBS) (>= 7.0 mmol.L(-1)). Forty-two percent (n = 16/38) of
      suboptimally controlled diabetics (HbA1c > 7.0%) had an elevated RBS (>= 11.1
      mmol.L(-1)), and 86% (n = 31/36) had an elevated FBS (>= 7.0 mmol.L(-1)).
      DISCUSSION: Many elective surgical patients are at risk for unrecognized
      postoperative hyperglycemia and associated adverse outcomes. Random blood sugar
      testing has limited value and HbA1c may be a more appropriate test for the
      preoperative assessment of diabetic patients.

PMID- 24585232
TI  - Successful one-stage extraction of an intracardiac and intravenous leiomyoma
      through the right atrium under transesophageal ultrasound monitoring.
AB  - PURPOSE: Intravenous leiomyomatosis is a rare disorder characterized by benign
      smooth-muscle tumours, termed leiomyomas, which originate from uterine leiomyomas
      or pelvic veins. Tumours may extend into the right-sided heart chambers, termed
      intracardiac leiomyomatosis (ICLM), and may be potentially life-threatening due
      to mechanical interference with cardiac structures or pulmonary arteries. While
      surgical excision is the optimal therapy, incomplete retrieval of a tumour or
      fatal retroperitoneal hemorrhage may occur. We present a case where
      intraoperative transesophageal ultrasound (TEU) guided complete removal of an
      intracardiac leiomyoma in a single-stage surgery solely through the right atrium
      without vein injury. CLINICAL FEATURES: A 46-yr-old female patient presented with
      a two-week history of exertional dyspnea, palpitations, and syncope. Preoperative
      imaging modalities revealed a continuous solid mass extending from the inferior
      vena cava (IVC) into the right atrium, and the patient subsequently underwent
      open heart surgery for tumour removal and definitive diagnosis. A systematic
      intraoperative TEU examination performed before resection showed that the
      serpentine tumour was free from any attachment to the IVC and the heart.
      Furthermore, the diameter of the intracardiac end of the tumour was wider than
      that of the IVC. Given these findings, the surgeons carefully drew the cord-like
      tumour out of the right atrium under close TEU monitoring without vein injury.
      Post-extraction TEU examination showed complete removal of the tumour.
      Microscopic examination of the specimen confirmed the diagnosis of intravenous
      leiomyomatosis. CONCLUSIONS: For cases with ICLM, intraoperative TEU plays a
      significant role in helping to plan the surgical approach, monitor the movement
      of the tumour and the IVC during the extraction, and assess the completeness of
      tumour resection.

PMID- 24585233
TI  - Perioperative management of an IgA-deficient recipient of a double-lung
      transplant.
AB  - PURPOSE: When exposed in the perioperative period to blood components containing
      immunoglobulin (Ig)A IgA-sensitized IgA-deficient patients are at an increased
      risk of transfusion-associated anaphylaxis. We present the case of an IgA
      deficient patient whose candidacy for double-lung transplantation was under
      review in the preoperative period. CLINICAL FEATURES: A 49-yr-old patient with
      end-stage chronic obstructive lung disease secondary to deficiencies in IgA and
      IgG subclasses was being assessed for double-lung transplantation. Early
      recognition of the ramifications of perioperative transfusion prompted
      consultation with the transfusion medicine service. This in turn facilitated
      specialized laboratory testing and the coordinated provision of appropriate blood
      products for the unpredictable date of transplantation. The theoretical systemic
      risks of a non-IgA-deficient graft on the sensitized IgA-deficient host were
      considered. To affirm the patient's candidacy for transplantation, he was
      ultimately challenged preoperatively with IgA-containing products in a controlled
      intensive-care setting. CONCLUSION: Through a multidisciplinary approach
      [corrected], a successful transplantation outcome was achieved in an IgA
      deficient patient undergoing major surgery. Strategies to mitigate risk include
      the procurement and transfusion of IgA-deficient components, which may be
      challenging or untenable in emergent perioperative settings.

PMID- 24585245
TI  - [Water-cooled laser sealing of lung tissue in an ex-vivo ventilated porcine lung
      model].
AB  - INTRODUCTION: Laser resections of lung metastases are followed by air leaks from
      the parenchymal defect. Large surfaces after metastasectomy are closed by sutures
      or sealants while smaller areas are frequently sealed thermally by cautery or
      laser. In this study two different techniques of thermal sealing of lung tissue
      with laser light are investigated. AIM AND METHODS: Carbonisation of lung tissue
      during thermal sealing appears at temperatures higher than 180  degrees C.
      Hypothetically this is contraproductive to haemo- as well as to pneumostasis. In
      this experimental study thermal laser sealing with and without carbonisation is
      investigated. In one series tissue temperatures higher than 100  degrees C are
      avoided by water dropping from the tip of the light guide onto the parenchymal
      leak. In the other series carbonisation appeared because the laser light was
      applied in the non-contact mode without tissue cooling. The characteristics of
      the laser were 40 W, 1350 nm continuous mode. Air leaks (Vt) were measured with a
      simple and fast technique with high precision. The sealing effect of either
      series was defined as S = (1-Vt/V0) and the difference of S was statistically
      examined. RESULTS: The basic values V0 before sealing were about the same in both
      series. The air leaks Vt after 15, 30 and 45 s of sealing varied significantly in
      both series (p = 0.03). During simultaneous cooling the sealing effect was
      increasing with the duration of laser application, while it became worse in the
      series without cooling. Histological examination of the sealing zone showed only
      coagulation of the tissue, while ruptured alveolae could be seen more often in
      the non-cooled sealing area. DISCUSSION: It could be shown in the ex-vivo lung
      model that laser sealing of parenchymal leaks is improved by simultaneous cooling
      during laser application. Non cooled laser sealing seems to heat up the tissue
      abruptly and create carbonisation followed by multiple ruptures of alveola and
      small airways. In accordance with our clinical experience this experimental study
      confirms that laser sealing for pneumostasis after metastasectomy can be improved
      by simultaneously cooling the resection area when treated with the laser.

PMID- 24585246
TI  - Patterns of infection by intestinal parasites in sympatric howler monkey
      (Alouatta palliata) and spider monkey (Ateles geoffroyi) populations in a
      tropical dry forest in Costa Rica.
AB  - In primate populations, endoparasite species richness and prevalence are
      associated with host traits such as reproductive and social status, age, sex,
      host population density, and environmental factors such as humidity. We analyzed
      the species richness and prevalence of intestinal parasites in two sympatric
      primate populations, one of Alouatta palliata and one of Ateles geoffroyi, found
      in a tropical dry forest in Costa Rica. We identified three species of intestinal
      parasites (Controrchis sp., Trypanoxyuris sp., and Strongyloides sp.) in these
      two primate species. We did not find any differences in species richness between
      the primate species. However, the prevalences of Controrchis sp. and
      Trypanoxyuris sp. were higher in Alouatta palliata. Similarly, males and
      lactating females of Alouatta palliata showed higher Controrchis sp. prevalences.
      We did not observe any differences in parasite richness and prevalence between
      seasons. Infectious diseases in endangered primate populations must be considered
      in conservation strategies, especially when defining protected areas.

PMID- 24585247
TI  - Effect of photoperiod on characteristics of semen obtained by electroejaculation
      in stump-tailed macaques (Macaca arctoides).
AB  - Some environmental variables determining seasonal reproduction in mammals are
      temperature, humidity, food availability, and photoperiod. Among these,
      photoperiod is considered the main regulator of primates' seasonal reproduction,
      thus the latitudinal distribution of primate populations is a key factor
      determining the appearance of seasonal reproduction. The present work presents
      supporting discrete seasonality in male stump-tailed macaques (Macaca arctoides).
      We investigated whether semen quality and testosterone covaried with Mexico
      City's photoperiod and relative humidity by analyzing variations in the portions
      that form the ejaculate: the seminal liquid, the seminal coagulum, and the
      copulatory plug. Five male adult stump-tailed macaques were electroejaculated
      once a month, obtaining three semen samples per male, from August 2011 to July
      2012 (except for December 2011) (n = 165). Our results showed that stump-tailed
      macaque sperm counts were significantly different between the portions of the
      ejaculate. The seminal coagulum contained the significantly largest number of
      spermatozoids, followed by the copulatory plug and the seminal fluid. Photoperiod
      and relative humidity had major influence on the sperm count in the seminal
      coagulum and the testosterone concentrations. Testosterone reached its highest
      values around the time when days and nights lasted the same hours, decreasing
      when days either grew longer or became shorter. Concerning relative humidity,
      sperm counts in the seminal coagulum were highly variable on dry days, but
      decreased as the relative humidity increased. We conclude that stump-tailed
      macaques have a discrete seasonality, occurring in spring and fall when macaques'
      reproductive condition and readiness for postcopulatory intrasexual competition
      increase.

PMID- 24585249
TI  - SCGB2A1 is a novel prognostic marker for colorectal cancer associated with
      chemoresistance and radioresistance.
AB  - We recently showed that liver metastatic tissue from patients with colorectal
      cancer (CRC) was a useful model for identifying novel, hypoxia-inducible genes
      and prognostic markers. We showed that the expression of secretoglobin, family
      2A, member 1 (SCGB2A1) was a potential prognostic factor for CRC. Here, we
      further evaluated the prognostic impact and function of SCGB2A1 in 222 patients
      with CRC. The impact of SCGB2A1 expression on disease-free survival (DFS) and
      overall survival (OS) was assessed with mRNA expression profiling. The function
      of SCGB2A1 was analyzed by evaluating mRNA expression profiles in cells derived
      from patients with CRC and by testing the effects of transfecting SCGB2A1 into
      different CRC-derived cell lines. We evaluated the effects of SCGB2A1 on
      proliferation, chemosensitivity, radiation sensitivity and sphere formation.
      Univariate and multivariate analyses indicated that the expression of SCGB2A1 was
      an independent prognostic factor for CRC (p<0.05), together with lymph node
      metastasis (p<0.05). Enforced expression of SCGB2A1 in CRC-derived cell lines
      promoted proliferation (DLD1, SW480 and LoVo cells; p<0.05), decreased
      chemosensitivity to 5-fluorouracil and oxaliplatin (DLD1 and SW480 cell lines;
      p<0.05), and significantly increased the viability of irradiated cells (DLD1,
      SW480 and LoVo cell lines; p<0.05). SCGB2A1 expression was also correlated to
      cancer stemness-related genes (Wnt, Zeb1 and Twist). Consistent with this
      correlation, SCGB2A1 expressing cells (SW480) showed increased sphere formation
      (p<0.05). These results indicated that SCGB2A1 represented a novel, prognostic
      factor for CRC, and that expression of SCGB2A1 correlated with chemoresistance,
      radioresistance and cancer cell stemness.

PMID- 24585250
TI  - What is Known About Health and Morbidity in the Pediatric Population of Muslim
      Bedouins in Southern Israel: A Descriptive Review of the Literature from the Past
      Two Decades.
AB  - The Bedouins comprise one of the ethnic groups in Israeli society. They are
      Muslims, most of who live in the Negev desert region of southern Israel and live
      by their unique traditions and customs. At the present they are going through a
      period of "society in transition", a unique condition that has ramifications for
      health and morbidity. In recent years the number of publications on the health of
      Bedouins in the Negev has increased. Recognition of unique socio-economic
      features, characteristics of health and diseases can help the medical team treat
      various health problems in this population as well as other populations with
      similar characteristics. In the present paper we survey and discuss publications
      on the health of Bedouin children over the past 20 years.

PMID- 24585251
TI  - Linkage disequilibrium and population-structure analysis among Capsicum annuum L.
      cultivars for use in association mapping.
AB  - Knowledge of population structure and linkage disequilibrium among the worldwide
      collections of peppers currently classified as hot, mild, sweet and ornamental
      types is indispensable for applying association mapping and genomic selection to
      improve pepper. The current study aimed to resolve the genetic diversity and
      relatedness of Capsicum annuum germplasm by use of simple sequence repeat (SSR)
      loci across all chromosomes in samples collected in 2011 and 2012. The physical
      distance covered by the entire set of SSRs used was 2,265.9 Mb from the 3.48-Gb
      hot-pepper genome size. The model-based program STRUCTURE was used to infer five
      clusters, which was further confirmed by classical molecular-genetic diversity
      analysis. Mean heterozygosity of various loci was estimated to be 0.15. Linkage
      disequilibrium (LD) was used to identify 17 LD blocks across various chromosomes
      with sizes from 0.154 Kb to 126.28 Mb. CAMS-142 of chromosome 1 was significantly
      associated with both capsaicin (CA) and dihydrocapsaicin (DCA) levels. Further,
      CAMS-142 was located in an LD block of 98.18 Mb. CAMS-142 amplified bands of 244,
      268, 283 and 326 bp. Alleles 268 and 283 bp had positive effects on both CA and
      DCA levels, with an average R(2) of 12.15 % (CA) and 12.3 % (DCA). Eight markers
      from seven different chromosomes were significantly associated with fruit weight,
      contributing an average effect of 15 %. CAMS-199, HpmsE082 and CAMS-190 are the
      three major quantitative trait loci located on chromosomes 8, 9, and 10,
      respectively, and were associated with fruit weight in samples from both years of
      the study. This research demonstrates the effectiveness of using genome-wide SSR
      based markers to assess features of LD and genetic diversity within C. annuum.

PMID- 24585252
TI  - Development and characterization of genomic SSR markers in Cynodon transvaalensis
      Burtt-Davy.
AB  - Simple sequence repeat (SSR) markers are a major molecular tool for genetic and
      genomic research that have been extensively developed and used in major crops.
      However, few are available in African bermudagrass (Cynodon transvaalensis Burtt
      Davy), an economically important warm-season turfgrass species. African
      bermudagrass is mainly used for hybridizations with common bermudagrass [C.
      dactylon var. dactylon (L.) Pers.] in the development of superior interspecific
      hybrid turfgrass cultivars. Accordingly, the major objective of this study was to
      develop and characterize a large set of SSR markers. Genomic DNA of C.
      transvaalensis '4200TN 24-2' from an Oklahoma State University (OSU) turf nursery
      was extracted for construction of four SSR genomic libraries enriched with
      [CA](n), [GA](n), [AAG](n), and [AAT](n) as core repeat motifs. A total of 3,064
      clones were sequenced at the OSU core facility. The sequences were categorized
      into singletons and contiguous sequences to exclude redundancy. From the two
      sequence categories, 1,795 SSR loci were identified. After excluding duplicate
      SSRs by comparison with previously developed SSR markers using a nucleotide basic
      local alignment tool, 1,426 unique primer pairs (PPs) were designed. Out of the
      1,426 designed PPs, 981 (68.8 %) amplified alleles of the expected size in the
      donor DNA. Polymorphisms of the SSR PPs tested in eight C. transvaalensis plants
      were 93 % polymorphic with 544 markers effective in all genotypes. Inheritance of
      the SSRs was examined in six F(1) progeny of African parents 'T577' * 'Uganda',
      indicating 917 markers amplified heritable alleles. The SSR markers developed in
      the study are the first large set of co-dominant markers in African bermudagrass
      and should be highly valuable for molecular and traditional breeding research.

PMID- 24585254
TI  - Assessing security technology's impact: old tools for new problems.
AB  - The general idea developed in this paper from a sociological perspective is that
      some of the foundational categories on which the debate about privacy, security
      and technology rests are blurring. This process is a consequence of a blurring of
      physical and digital worlds. In order to define limits for legitimate use of
      intrusive digital technologies, one has to refer to binary distinctions such as
      private versus public, human versus technical, security versus insecurity to draw
      differences determining limits for the use of surveillance technologies. These
      distinctions developed in the physical world and are rooted in a cultural
      understanding of pre-digital culture. Attempts to capture the problems emerging
      with the implementation of security technologies using legal reasoning encounter
      a number of problems since law is by definition oriented backwards, adapting new
      developments to existing traditions, whereas the intrusion of new technologies in
      the physical world produces changes and creates fundamentally new problems.

PMID- 24585253
TI  - Optimization of mRNA design for protein expression in the crustacean Daphnia
      magna.
AB  - The water flea Daphnia is a new model organism for ecological, evolutionary, and
      toxicological genomics. Detailed functional analysis of genes newly discovered
      through genomic approaches often requires overexpression of the identified
      protein. In the present study, we report the microinjection of in vitro
      synthesized RNAs into the eggs as a method for overexpressing ubiquitous proteins
      in Daphnia magna. We injected a 1.3-kb mRNA that coded for the red fluorescent
      protein (DsRed2) flanked by UTRs from the ubiquitously expressed elongation
      factor 1alpha-1 (EF1alpha-1) into D. magna embryos. DsRed2 fluorescence in the
      embryos was measured 24 h after microinjection. Unexpectedly, the reporter RNA
      containing the 522-bp full-length EF1alpha-1 3' UTR failed to induce
      fluorescence. To assess reporter expression, the length of the 3' UTR that
      potentially contained negative regulatory elements of protein expression,
      including AU-rich regions and Musashi binding elements, was serially reduced from
      the 3' end. Assessing all injected RNA alternatives, mRNA containing the first 60
      bp of the 3' UTR gave rise to the highest fluorescence, 14 times the Daphnia auto
      fluorescence. In contrast, mRNA lacking the entire 3' UTR hardly induced any
      change in fluorescence intensity. This is the first evaluation of UTRs of mRNAs
      delivered into Daphnia embryos by microinjection for overexpressing proteins. The
      mRNA with truncated 3' UTRs of Daphnia EF1alpha-1 will be useful not only for
      gain-of-function analyses but also for labeling proteins and organelles with
      fluorescent proteins in Daphnia.

PMID- 24585255
TI  - Metals analysis of agricultural soils via portable X-ray fluorescence
      spectrometry.
AB  - To assess the applicability of portable X-ray fluorescence (PXRF) spectrometry
      for metals analysis, total concentrations of As, Pb, Cu, and Zn in 47
      agricultural soils were determined using in situ PXRF analysis, ex situ PXRF
      analysis, and conventional laboratory analysis. The correlation regression
      parameters of PXRF data with the data of conventional analysis were significantly
      improved upon going from in situ to ex situ, indicating that improvement of the
      ex situ PXRF data quality was achieved thorough sample preparation. Use of PXRF
      in situ was inferior to other analyses, especially when attempting to quantify
      relatively low levels of metals in agricultural soils. A high degree of linearity
      and similar spatial distribution existed between ex situ PXRF and laboratory
      analysis, suggesting that PXRF can be used in rapid detection or screening of
      agricultural soils, but is best followed with additional sample preparation ex
      situ and laboratory confirmation. 

PMID- 24585256
TI  - Experience with the surgical treatment of atrioventricular septal defect with
      left ventricular outflow tract obstruction.
AB  - OBJECTIVES: We sought to determine the prevalence, morphology, surgical methods
      and results of surgery for left ventricular outflow tract obstruction (LVOTO)
      associated with atrioventricular septal defect (AVSD). METHODS: Correction of
      AVSD was performed in 615 patients. Twenty-three (3.7%) patients with LVOTO were
      identified. Sixteen (70%) of them had partial and 7 (30%) had complete AVSD.
      Surgery for AVSD was performed at a median of 0.6 years (mean 2.1 +/- 3.0 years),
      and surgery for LVOTO at a median of 3.4 years (mean 4.7 +/- 3.5 years). The
      point and period prevalence of LVOTO in AVSD were determined. Detailed
      morphological study, individualized repair of AVSD with LVOTO and long-term
      follow-up were performed. Early and long-term results were analysed. RESULTS: The
      point prevalence of LVOTO at the time of AVSD repair was 1.3%. The period
      prevalence of LVOTO was 3.7% in course of 8.3 +/- 6.0 (0-18.4) years and 191.4
      patient-years following AVSD repair. Causes of LVOTO were fibromuscular membrane
      (n = 17), septal hypertrophy (n = 17), abnormal atrioventricular (AV) valve (n =
      9), muscular bands (n = 3), fibrous strands (n = 4) and stenotic aortic valve (n
      = 2). Usually, a combination of several obstructive lesions was present. LVOTO
      was present at the time of AVSD repair in 8 patients (35%) and developed after
      repair in 15 (65%) patients. Membrane excision (n = 17), myectomy (n = 17),
      excision of abnormal AV valvar tissue (n = 8), excision of muscular bands and
      fibrous strands (n = 6), AV valve replacement (n = 2) and aortic valvotomy (n =
      2) were required. There was 1 (4%) early and 1 (4%) late death. Six (29%)
      survivors required reoperation for recurrence of LVOTO at an average interval of
      6.3 +/- 3.2 years after surgery. The actuarial survival at 1 and 10 years was 96
      and 88%, respectively. The actuarial freedom from reoperation for LVOTO was 80,
      40 and 20% at 6, 10 and 15 years after surgery, respectively. Eighteen (78%)
      patients remain in good condition at mean 6.0 +/- 5.5 years after surgery.
      CONCLUSIONS: The point prevalence of LVOTO at the time of AVSD repair was 1.3%,
      and period prevalence 3.7%. Fibromuscular membrane, septal hypertrophy and valvar
      attachments represent the most common causes of LVOTO. Usually, more structures
      are involved. The repair must be individualized. The presence of LVOTO increases
      the need for reoperation.

PMID- 24585257
TI  - Racism, segregation, and risk of obesity in the Black Women's Health Study.
AB  - We assessed the relation of experiences of racism to the incidence of obesity and
      the modifying impact of residential racial segregation in the Black Women's
      Health Study, a follow-up study of US black women. Racism scores were created
      from 8 questions asked in 1997 and 2009 about the frequency of "everyday" racism
      (e.g., "people act as if you are dishonest") and of "lifetime" racism (e.g.,
      unfair treatment on the job). Residential segregation was measured by linking
      participant addresses to 2000 and 2010 US Census block group data on the percent
      of black residents. We used Cox proportional hazard models to estimate incidence
      rate ratios and 95% confidence intervals. Based on 4,315 incident cases of
      obesity identified from 1997 through 2009, both everyday racism and lifetime
      racism were positively associated with increased incidence. The incidence rate
      ratios for women who were in the highest category of everyday racism or lifetime
      racism in both 1997 and 2009, relative to those in the lowest category, were 1.69
      (95% confidence interval: 1.45, 1.96; Ptrend < 0.01) and 1.38 (95% confidence
      interval: 1.15, 1.66; Ptrend < 0.01), respectively. These associations were not
      modified by residential segregation. These results suggest that racism
      contributes to the higher incidence of obesity among African American women. 

PMID- 24585258
TI  - Deposition fluxes of PCDD/Fs in the area surrounding a steel plant in northwest
      Italy.
AB  - The paper aims at investigating the contribution of a steel plant located in a
      rural area in northwestern Italy (700,000 tons of steel/year) to the deposition
      fluxes of Polychorinated Dibenzo-p-dioxins and Polychorinated dibenzofurans
      (PCDD/PCDFs) at local level through the analysis of sampling data, literature
      data, and air dispersion model (AERMOD)output data. Total measured deposition
      fluxes of PCDD/PCDFs in three monitoring stations were consistent with other
      studies carried out in Italy in urban and suburban areas and in rural European
      areas; while these were lower than those measured in other European
      urban/suburban areas or in sites influenced by industrial sources. Furthermore,
      the measured fluxes were also compared with the pattern of PCDD/Fs in ambient air
      sampled at the same sites in a previous study. This comparison showed a
      similarity between air concentration and deposition patterns of the samples
      collected at the three monitoring stations and a clear distinction of these from
      the source. The study was completed with AERMOD simulations, conducted with a
      mass mean particle diameter of 0.5 MUm, according to the particle size
      distribution of the samples collected at the source. AERMOD calculated deposition
      fluxes of two to three orders of magnitude lower than those measured in two
      monitoring points; while in the most distant monitoring station, the deposition
      fluxes were too low to be calculated by the model. The simulations confirmed that
      the most distant monitoring station was not subject to emissions from the steel
      plant. The analysis highlighted the limited influence of the source in the local
      PCDD/F deposition fluxes.

PMID- 24585260
TI  - Estimation of genetic parameters for preweaning growth traits of Brahman cattle
      in Southeastern Mexico.
AB  - The genetic parameters for Brahman cattle under the tropical conditions of Mexico
      are scarce. Therefore, heritabilities, additive direct and maternal correlations,
      and genetic correlations for birth weight (BW) and 205 days adjusted weaning
      weight (WW205) were estimated in four Brahman cattle herds in Yucatan, Mexico.
      Parameters were estimated fitting a bivariate animal model, with 4,531 animals in
      the relationship matrix, of which 2,905 had BW and 2,264 had WW205. The number of
      sires and dams identified for both traits were 122 and 962, respectively. Direct
      heritability estimates for BW and WW205 were 0.41 +/- 0.09 and 0.43 +/- 0.09, and
      maternal heritabilities were 0.15 +/- 0.07 and 0.38 +/- 0.08, respectively.
      Genetic correlations between direct additive and maternal genetic effects for BW
      and WW205 were -0.41 +/- 0.22 and -0.50 +/- 0.15, respectively. The direct
      genetic, maternal, and phenotypic correlations between BW and WW205 were 0.77 +/-
      0.09, 0.61 +/- 0.18, and 0.35, respectively. The moderate to high genetic
      parameter estimates suggest that genetic improvement by selection is possible for
      those traits. The maternal effects and their correlation with direct effects
      should be taken into account to reduce bias in genetic evaluations. 

PMID- 24585263
TI  - [Kissing molars. A peculiar radiologic finding].

PMID- 24585261
TI  - The effect of different pretreatment methods of PMMA-based crowns on the long
      term tensile bond strength to dentin abutments.
AB  - OBJECTIVES: The objective of the study was to test the effect of different
      pretreatments on tensile bond strength (TBS) of adhesively bonded CAD/CAM
      generated polymethyl methacrylate (PMMA) crowns to dentin. MATERIALS AND METHODS:
      Two hundred human molars were prepared and divided into 20 groups (n = 10/group).
      PMMA crowns were pretreated thusly: Monobond Plus/Heliobond (MH), Visio.link
      (VL), Ambarino P60 (AM), VP connect (VP), and nontreated as control groups (CG).
      Two resin cements were used for cementation of crowns: Clearfil SA Cement (CSA)
      and Variolink II (VAR). TBS was measured initially (24 h water storage, 37 
      degrees C) and after aging (5,000 thermal cycles, 5/55  degrees C). TBS was
      analyzed using one-way ANOVA with Scheffe post hoc, unpaired Student t, Mann
      Whitney U, Kruskal-Wallis H, and chi-squared tests. RESULTS: Within CSA,
      pretreatment with MH and VL showed higher initial TBS compared with AM-treated
      groups. All other groups showed no statistical differences. For MH, VL, AM, and
      VP in combination with CSA, a negative impact of aging was observed (p < 0.001),
      whereas in all VAR groups, no impact was measured. Pretreatment with MH (p =
      0.001) and VP (p = 0.008) presented higher initial TBS for CSA than for VAR.
      After aging, MH (p = 0.025) and VL (p = 0.034) cemented with VAR showed higher
      results than CSA. CONCLUSIONS: All tested groups showed very low TBS values.
      Pretreatments with MH, VL, and VP have minimally improved the tensile strength
      after aging. CLINICAL RELEVANCE: Although the tensile strength results were low,
      crowns adhesively cemented with pretreatments with MH, VL, and VP showed, after
      aging, a higher tensile strength than nontreated groups.

PMID- 24585265
TI  - No post-conditioning in the human heart with thrombolysis in myocardial
      infarction flow 2-3 on admission.
AB  - AIMS: Proof-of-concept evidence suggests that mechanical ischaemic post
      conditioning (PostC) reduces infarct size when applied immediately after culprit
      coronary artery re-opening in ST-elevation myocardial infarction (STEMI) patients
      with thrombolysis in myocardial infarction 0-1 (TIMI 0-1) flow grade at
      admission. Whether PostC might also be protective in patients with a TIMI 2-3
      flow grade on admission (corresponding to a delayed application of the post
      conditioning algorithm) remains undetermined. METHODS AND RESULTS: In this multi
      centre, randomized, single-blinded, controlled study, STEMI patients with a 2-3
      TIMI coronary flow grade at admission underwent direct stenting of the culprit
      lesion, followed (PostC group) or not (control group) by four cycles of (1 min
      inflation/1 min deflation) of the angioplasty balloon to trigger post
      conditioning. Infarct size was assessed both by cardiac magnetic resonance at Day
      5 (primary endpoint) and cardiac enzymes release (secondary endpoint). Ninety
      nine patients were prospectively enrolled. Baseline characteristics were
      comparable between control and PostC groups. Despite comparable size of area at
      risk (AAR) (38 +/- 12 vs. 38 +/- 13% of the LV circumference, respectively, P =
      0.89) and similar time from onset to intervention (249 +/- 148 vs. 263 +/- 209
      min, respectively, P = 0.93) in the two groups, PostC did not significantly
      reduce cardiac magnetic resonance infarct size (23 +/- 17 and 21 +/- 18 g in the
      treated vs. control group, respectively, P = 0.64). Similar results were found
      when using creatine kinase and troponin I release, even after adjustment for the
      size of the AAR. CONCLUSION: This study shows that infarct size reduction by
      mechanical ischaemic PostC is lost when applied to patients with a TIMI 2-3 flow
      grade at admission. This indicates that the timing of the protective intervention
      with respect to the onset of reperfusion is a key factor for preventing lethal
      reperfusion injury in STEMI patients. CLINICAL TRIAL NUMBER: NCT01483755.

PMID- 24585266
TI  - Statin therapy and long-term adverse limb outcomes in patients with peripheral
      artery disease: insights from the REACH registry.
AB  - AIMS: Due to a high burden of systemic cardiovascular events, current guidelines
      recommend the use of statins in all patients with peripheral artery disease
      (PAD). We sought to study the impact of statin use on limb prognosis in patients
      with symptomatic PAD enrolled in the international REACH registry. METHODS:
      Statin use was assessed at study enrolment, as well as a time-varying covariate.
      Rates of the primary adverse limb outcome (worsening claudication/new episode of
      critical limb ischaemia, new percutaneous/surgical revascularization, or
      amputation) at 4 years and the composite of cardiovascular death/myocardial
      infarction/stroke were compared among statin users vs. non-users. RESULTS: A
      total of 5861 patients with symptomatic PAD were included. Statin use at baseline
      was 62.2%. Patients who were on statins had a significantly lower risk of the
      primary adverse limb outcome at 4 years when compared with those who were not
      taking statins [22.0 vs. 26.2%; hazard ratio (HR), 0.82; 95% confidence interval
      (CI), 0.72-0.92; P = 0.0013]. Results were similar when statin use was considered
      as a time-dependent variable (P = 0.018) and on propensity analysis (P < 0.0001).
      The composite of cardiovascular death/myocardial infarction/stroke was similarly
      reduced (HR, 0.83; 95% CI, 0.73-0.96; P = 0.01). CONCLUSION: Among patients with
      PAD in the REACH registry, statin use was associated with an ~18% lower rate of
      adverse limb outcomes, including worsening symptoms, peripheral
      revascularization, and ischaemic amputations. These findings suggest that statin
      therapy not only reduces the risk of adverse cardiovascular events, but also
      favourably affects limb prognosis in patients with PAD.

PMID- 24585267
TI  - Diuretic response in acute heart failure: clinical characteristics and prognostic
      significance.
AB  - AIM: Diminished diuretic response is common in patients with acute heart failure,
      although a clinically useful definition is lacking. Our aim was to investigate a
      practical, workable metric for diuretic response, examine associated patient
      characteristics and relationships with outcome. METHODS AND RESULTS: We examined
      diuretic response (defined as Delta weight kg/40 mg furosemide) in 1745
      hospitalized acute heart failure patients from the PROTECT trial. Day 4 response
      was used to allow maximum differentiation in responsiveness and tailoring of
      diuretic doses to clinical response, following sensitivity analyses. We
      investigated predictors of diuretic response and relationships with outcome. The
      median diuretic response was -0.38 (-0.80 to -0.13) kg/40 mg furosemide. Poor
      diuretic response was independently associated with low systolic blood pressure,
      high blood urea nitrogen, diabetes, and atherosclerotic disease (all P < 0.05).
      Worse diuretic response independently predicted 180-day mortality (HR: 1.42; 95%
      CI: 1.11-1.81, P = 0.005), 60-day death or renal or cardiovascular
      rehospitalization (HR: 1.34; 95% CI: 1.14-1.59, P < 0.001) and 60-day HF
      rehospitalization (HR: 1.57; 95% CI: 1.24-2.01, P < 0.001) in multivariable
      models. The proposed metric-weight loss indexed to diuretic dose-better captures
      a dose-response relationship. Model diagnostics showed diuretic response provided
      essentially the same or slightly better prognostic information compared with its
      individual components (weight loss and diuretic dose) in this population, while
      providing a less biased, more easily interpreted signal. CONCLUSIONS: Worse
      diuretic response was associated with more advanced heart failure, renal
      impairment, diabetes, atherosclerotic disease and in-hospital worsening heart
      failure, and predicts mortality and heart failure rehospitalization in this post
      hoc, hypothesis-generating study.

PMID- 24585269
TI  - Allograft reconstruction for extensor mechanism injuries.
AB  - Previous case reports have documented the successful use of allograft for
      extensor mechanism reconstruction. We hypothesized that extensor mechanism
      reconstruction with allograft would restore extensor power and allow patients to
      return to a relatively high activity level. Between 2000 and 2007, 17 patients
      (18 knees) underwent extensor mechanism reconstruction with either nonirradiated
      Achilles or whole bone-patellar tendon-bone allograft at our institution. Two
      patients were lost to follow-up and one underwent a total knee arthroplasty and
      was considered a failure. The remaining 14 patients (15 knees) returned for
      clinical and radiographic evaluation at a minimum 24 months postoperatively.
      Patients completed questionnaires using the International Knee Documentation
      Committee (IKDC), Tegner, Lysholm, Knee Injury Osteoarthritis Outcome Score
      (KOOS), Noyes sports activity, and Short Form-12 (SF-12) scoring systems.
      Fourteen patients with an average age at surgery of 46.48 years (range, 18-70)
      returned for evaluation at a median follow-up of 52 months (range, 31-98 months).
      Twelve of the 14 patients underwent previous surgery before allograft
      reconstruction. Postoperatively, the median IKDC score was 74 (range, 28-90),
      Tegner 8 (range, 0.5-10), Lysholm 62 (range, 28-100), KOOS pain 92 (range, 36
      100), KOOS symptom 64 (range, 21-100), KOOS ADL 82 (range, 51-100), KOOS sport 50
      (range, 5-95), KOOS QOL 44 (range, 12.5-100), Noyes 90 (range, 5-100), SF-12
      physical 43 (range, 29-47), and SF-12 mental 49 (range, 28-64). All patients were
      able to perform a straight leg raise postoperatively. Five patients had an
      extensor lag at final evaluation averaging 8 degrees (range, 3-18). Thigh girth
      differential between the surgical and contralateral leg was 1.3 cm diameter.
      There were no postoperative infections or reruptures. Two patients required
      additional procedures. We believe extensor mechanism reconstruction with
      allograft is an effective salvage procedure in this challenging patient
      population. 

PMID- 24585268
TI  - Homozygous autosomal dominant hypercholesterolaemia in the Netherlands:
      prevalence, genotype-phenotype relationship, and clinical outcome.
AB  - AIMS: Homozygous autosomal dominant hypercholesterolaemia (hoADH), an orphan
      disease caused by mutations in low-density lipoprotein receptor (LDLR),
      apolipoprotein B (APOB), or proprotein convertase subtilisin-kexin type 9
      (PCSK9), is characterized by elevated plasma low-density lipoprotein-cholesterol
      (LDL-C) levels and high risk for premature cardiovascular disease (CVD). The
      exact prevalence of molecularly defined hoADH is unknown. Therefore, we
      investigated the prevalence and phenotypical characteristics of this disease in
      an open society, i.e. the Netherlands. METHODS AND RESULTS: The database of the
      nationwide ADH molecular diagnostic center was queried to identify all
      molecularly defined hoADH patients. Carriers of non-pathogenic mutations were
      excluded. Medical records were analysed for data regarding lipid levels and CVD
      events. Of 104,682 individuals screened for molecular defects, 49 were classified
      as hoADH (0.05%); 20 were true homozygotes, 25 were compound heterozygotes for
      LDLR mutations, and 4 were homozygous for APOB mutations. No bi-allelic PCSK9
      mutation carriers were identified. Consequently, the prevalence of hoADH was
      estimated to be ~1 : 300,000. Mean LDL-C levels prior to lipid-lowering treatment
      were 12.9 +/- 5.1 mmol/L (range 4.4-21.5 mmol/L). Surprisingly, only 50% of the
      patients met the clinical criteria for hoADH (LDL-C >13.0 mmol/L); 29% of
      patients suffered from a CVD event. CONCLUSION: The prevalence of molecularly
      defined hoADH is much higher and the clinical phenotype is more variable than
      previously assumed. In light of the fact that novel therapies are, or will be
      registered for the treatment of hoADH patients, an uniform definition of hoADH
      either as a phenotypic or molecular entity is warranted in order to identify
      patients who are considered to be eligible for these novel agents.

PMID- 24585271
TI  - Special focus: nitrogen cycling.

PMID- 24585270
TI  - A novel inhalable form of rifapentine.
AB  - Recent murine studies found that rifapentine, dosed daily, at least halved
      tuberculosis treatment times compared with standard rifampicin and isoniazid
      containing regimens. However, in humans, an inhalable form of rifapentine may be
      necessary to considerably shorten treatment duration because of the physiological
      barriers associated with oral therapy. The current study compares two inhalable
      rifapentine dry powders-a novel pure crystalline form and an amorphous form-by a
      series of in vitro tests. The crystalline and amorphous powders had a mass median
      aerodynamic size of 1.68 +/- 0.03 and 1.92 +/- 0.01 MUm, respectively, associated
      with a fine particle fraction of 83.2 +/- 1.2% and 68.8 +/- 2.1%, respectively. A
      quinone degradation product was identified in the amorphous powder stored for 1
      month, whereas the crystalline form remained chemically stable after storage at
      both 0% and 60% relative humidity, 25 degrees C, for at least 3 months.
      Solubilized rifapentine was well tolerated by pulmonary tissue and macrophage
      cells up to approximately 50 MUM. The accumulation of rifapentine within alveolar
      macrophage cells was significantly higher than for rifampicin, indicating
      enhanced delivery to infected macrophages. The novel inhalable crystalline form
      of rifapentine is suitable for targeted treatment of tuberculosis infection and
      may radically shorten treatment duration.

PMID- 24585275
TI  - Congenital and genetic disorders in the Sultanate of Oman. First attempt to
      assess healthcare needs.

PMID- 24585276
TI  - Blunt traumatic left atrial appendage rupture and cardiac herniation.
AB  - A 42-year-old man sustained blunt thoracic trauma after a motor vehicle accident.
      He underwent an urgent operation. Operative findings included a large hematoma, a
      4-cm tear in the left atrial appendage, and a long pleuropericardial rupture
      along the right phrenic nerve. We repaired the left atrial appendage without
      cardiopulmonary bypass, and closed the pericardial defect primarily. The patient
      recovered fully and was discharged on the 6th postoperative day. 

PMID- 24585277
TI  - Thymectomy by video-assisted thoracoscopy versus open surgical techniques.
AB  - OBJECTIVE: This study was conducted to compare operative variables and
      postoperative outcomes in adult patients with myasthenia gravis undergoing
      thymectomy through 3 different operative techniques: total median sternotomy,
      partial median sternotomy, and video-assisted thoracoscopy. METHODS: 30 patients
      aged 20-65 years were included in this study. They were subdivided into: group A:
      8 patients undergoing thymectomy through a total median sternotomy; group B: 9
      patients undergoing thymectomy through a partial median sternotomy; and group C:
      13 patients undergoing thymectomy through video-assisted thoracoscopy.
      Preoperative, intraoperative, and postoperative variables, and mortality were
      compared among groups. RESULTS: Preoperative variables were well matched in all
      groups. Operative time was significantly longer in group C. There was no
      intraoperative complication in any group. Postoperative length of hospital stay
      was significantly shorter in group C. Postoperative complications occurred in 3
      (10%) patients, mostly in groups A and B. There was no perioperative mortality in
      any group. CONCLUSIONS: Video-assisted thymectomy is as effective as the
      traditional open surgical approaches for thymectomy in the management of patients
      with myasthenia gravis. In addition, the improved cosmesis of the video-assisted
      approach ideally should lead to earlier thymectomy in patients with myasthenia
      gravis.

PMID- 24585278
TI  - Traumatic intrathoracic tracheobronchial injuries: a study of 78 cases.
AB  - BACKGROUND: Tracheobronchial injuries are encountered with increasing frequency
      because of improvements in pre-hospital care. We reviewed our experience of these
      injuries to determine how to better recognize them and facilitate their correct
      management. METHODS: Patients with traumatic non-iatrogenic intrathoracic
      tracheobronchial injuries managed in 2 tertiary centers in Saudi Arabia between
      2000 and 2012, were studied. Clinical presentation, diagnostic evaluation,
      management, and outcome were reviewed. RESULTS: 78 patients with tracheobronchial
      injuries were included in this study. They were divided into 2 groups according
      to the management strategy. Forty-seven patients who were managed conservatively,
      and 31 underwent surgery. Surgery allowed shorter intensive care unit and
      hospital stays; otherwise, the results were comparable between the two groups.
      CONCLUSIONS: Early recognition and expedient appropriate management are essential
      in these potentially lethal injuries. Operative management can be achieved with
      acceptable mortality, and conservative treatment should be considered as a
      valuable alternative to the well-established surgical treatment.

PMID- 24585279
TI  - Incidental finding of a large right coronary artery aneurysm.

PMID- 24585280
TI  - Chest tube injury penetrating the right middle lobe of the lung.

PMID- 24585281
TI  - Hands-free approach for the left atrial appendage in Cox maze IV.
AB  - Surgical excision of the left atrial appendage is an essential key in the Cox
      maze IV procedure. Management of very thin, friable, and delicate tissue in the
      base of the left atrial appendage can be difficult. We have designed a simple
      method to expose adequately without handling the base of the left atrial
      appendage. With this technique, the risk of bleeding due to excessive traction or
      manipulation of the heart is dramatically reduced. 

PMID- 24585282
TI  - A modified cryo-maze procedure via the superior transseptal approach.
AB  - The superior transseptal approach provides excellent exposure for mitral valve
      reconstruction. For atrial fibrillation, cryoablation is less invasive, simpler,
      and safer than the Cox maze operation. Combining the superior transseptal
      approach and cryoablation for mitral valve procedures yields a high recovery rate
      from atrial fibrillation, similar to that of radiofrequency ablation.
      Cryoablation-related complications such as thromboembolic events or requirement
      for a permanent pacemaker were not observed in our consecutive series.
      Cryoablation is also cost-effective. 

PMID- 24585284
TI  - Solitary fibrous tumor as a cause of chronic cough.

PMID- 24585283
TI  - Mediastinal sarcoid-like reaction after colon adenocarcinoma resection.
AB  - We report a rare case of mediastinal sarcoid-like reaction presenting 5 years
      after colon adenocarcinoma resection. The lack of clinical and biochemical
      features suggestive of sarcoidosis and the high (18)F-fluorodeoxyglucose uptake
      in mediastinal adenopathy, not seen previously, led us to suspect cancer
      recurrence. Pathological diagnosis obtained with a thoracoscopic biopsy confirmed
      sarcoidosis. Mediastinal adenopathies need to be confirmed pathologically to
      avoid potential interpretative pitfalls leading to toxic overtreatment. 

PMID- 24585285
TI  - Radiofrequency ablation of atrial fibrillation during mitral valve surgery.
AB  - OBJECTIVES: Atrial fibrillation is the most common form of arrhythmia in mitral
      valve disease. Radiofrequency ablation is most commonly used for atrial
      fibrillation ablation during mitral valve surgery. METHODS: This prospective
      study evaluated the midterm outcomes of intraoperative radiofrequency atrial
      fibrillation ablation during mitral valve surgery. RESULTS: 52 patients were
      eligible for the study. Fifteen (28.8%) had a transseptal approach and 37 had a
      left atriotomy. Mitral valve replacement was performed in 16 patients, mitral
      valve repair in 31, and tricuspid repair in 8. Mean crossclamp time was 58.14.+/-
      20.08 min, and mean cardiopulmonary bypass time was 71.28 +/- 20.31 min. The mean
      ablation time was 6.41 +/- 0.21 min. There was no postoperative mortality. Sinus
      rhythm was documented in 44 (84.6%) patients on discharge, and 8 (15.4%) were
      discharged with atrial fibrillation; 2 of them returned to sinus rhythm after 3
      months. After 12 months of follow-up, 46 (88.5%) patients were in sinus rhythm.
      CONCLUSION: Left atrial monopolar radiofrequency ablation during mitral valve
      surgery is a safe procedure with a high success rate.

PMID- 24585286
TI  - Long-term results of an open flexible prosthetic band for mitral insufficiency.
AB  - BACKGROUND: use of a prosthetic ring is an integral part of any mitral valve
      repair and can influence the long-term stability of the results. We evaluated the
      long-term results of the AnnuloFlex ring implanted as an open flexible band in
      patients affected by degenerative mitral disease. METHODS: between 2001 and 2010,
      82 patients (52 women, 30 men) with a mean age of 62 years, underwent repair of a
      prolapsing mitral valve with an AnnuloFlex band. One patient was reoperated on
      for a technical error and received a mechanical prosthesis, 3 were missing at
      follow-up, and the other 78 were prospectively followed up with clinical
      interviews and transthoracic echocardiography. RESULTS: the mean follow-up was
      7.0 +/- 1.8 years. Six patients died; 2 deaths were considered valve-related. The
      overall survival estimate at 10 years was 88.6% (95% confidence interval: 76.1%
      94.8%). Freedom from endocarditis was 97.1% (95% confidence interval: 89.1%
      98.5%). Freedom from thrombosis or hemorrhage was 93.7% (95% confidence interval:
      81.6%-97.9%). Freedom from new or increased regurgitation was 93.1% (95%
      confidence interval: 87.3%-97.3%). The cumulative freedom from any valve-related
      event was 78.6% (95% confidence interval: 69.7%-97.1%). A single case of systolic
      anterior motion occurred before hospital discharge. CONCLUSION: the long-term
      results of the AnnuloFlex band are excellent and stable.

PMID- 24585287
TI  - Aortic valve reconstruction using autologous pericardium for ages over 80 years.
AB  - BACKGROUND: We performed original aortic valve reconstruction using autologous
      pericardium; the feasibility for elderly patients is reviewed. METHODS: From
      April 2007 through September 2011, aortic valve reconstruction was carried out in
      86 patients over the age of 80 years. Twenty-seven patients were male and 59 were
      female. Mean age was 82.9 +/- 2.5 years. Seventy-two patients had aortic stenosis
      and 14 had aortic regurgitation. Mean preoperative surgical annular diameter was
      19.5 +/- 2.5 mm. There were 80 (90.7%) cases of small aortic annulus. Mean
      preoperative logistic EuroSCORE was 22.9 +/- 15.8. RESULTS: Isolated aortic valve
      reconstructions were performed in 51 patients. Concomitant procedures included
      coronary artery bypass grafting in 6, hemiarch aortic replacements in 6, 9 maze
      procedures, and some combinations. No conversion to valve replacement was
      required. Mean follow-up was 1243 days. There were 3 hospital deaths due to
      noncardiac causes. No reoperation was needed. Survival at 56 months was 87.0%. No
      thromboembolic event occurred. Echocardiography 3.5 years after surgery revealed
      an average peak pressure gradient of 14.6 +/- 3.8 mm Hg. No moderate or severe
      regurgitation was recorded. CONCLUSIONS: Aortic valve reconstruction is feasible
      for patients older than 80 years, resulting in good hemodynamics and a better
      quality of life, without anticoagulation.

PMID- 24585288
TI  - Is continuation of antiplatelets until coronary artery bypass safe in Asians?
AB  - BACKGROUND: Controversies have arisen about the risks of discontinuing
      antiplatelets prior to coronary artery bypass grafting. METHODS: We
      retrospectively studied the effects of different strategies of antiplatelet
      discontinuation prior to coronary artery bypass on perioperative bleeding and
      major adverse cardiovascular events in Asian patients in a single center in
      Singapore. RESULTS: 402 patients were divided into 4 groups: group A had no
      antiplatelets before surgery; antiplatelets were stopped for 5-7 days in group B;
      2-4 days in group C; and 0-1 day in group D. Compared to group B, group D had
      longer intensive care unit stays and more intraoperative transfusions of blood (p
      = 0.006) and blood products (p < 0.05). The 1-year major adverse cardiovascular
      event rate was higher in groups A and D (p = 0.027). Stopping antiplatelets
      within 24 h of surgery was one of multiple independent predictors of
      intraoperative transfusion but not the 1-year major adverse cardiovascular event
      rate. Patients on aspirin alone had less intraoperative transfusion of platelets
      and postoperative minor bleeding than those on combined therapy. CONCLUSION:
      Continuation of antiplatelets until 2 days before coronary artery bypass in Asian
      patients in our institution is unlikely to increase the risks of bleeding and
      perioperative transfusion. Taking antiplatelets within 24 h of surgery seems to
      be associated with a higher rate of 1-year major adverse cardiovascular events
      and bleeding, and an increased risk of blood product transfusion. Thirty-day and
      1-year major adverse cardiovascular event rates were higher in patients without
      antiplatelet treatment.

PMID- 24585289
TI  - Valvular repair or replacement for mitral endocarditis: 7-year cohort study.
AB  - BACKGROUND: A few studies have compared mitral valve repair and replacement in
      the setting of infective endocarditis, with varying results. We compared the
      characteristics and outcomes of mitral repair and replacement in endocarditis
      patients. METHODS: All patients undergoing mitral valve repair or replacement for
      active mitral endocarditis during 2005-2011 were included. Operative and follow
      up mortality, composite morbidity, recurrent endocarditis, and redo operations
      were prespecified endpoints for analyses. RESULTS: There were 25 and 35 patients
      undergoing mitral valve repair and replacement, respectively. They were followed
      up for 3.9 +/- 2.5 years. Valve replacement patients were older (p = 0.029), had
      a higher prevalence of intracardiac abscess (p = 0.035), previous endocarditis (p
      = 0.036), atrial fibrillation (p = 0.001), worse renal function (p = 0.013),
      higher risk scores (p = 0.004-0.020), and longer operation times (p < 0.001).
      Repair and replacement had similar rates of operative mortality (4.0% vs. 8.6%, p
      = 0.634), composite morbidity (16.0% vs. 28.6%, p = 0.357), survival (p = 0.564),
      recurrent endocarditis (p = 0.081), and redo operations (p = 0.813). Independent
      predictors of operative mortality were preoperative inotropic or intraaortic
      balloon pump support. The independent predictor of mortality during follow-up was
      dialysis. Independent predictors of composite morbidity were intracardiac abscess
      and hypercholesterolemia. The independent predictor of recurrent endocarditis was
      previous endocarditis, and the independent predictor of redo operation was
      previous stroke. CONCLUSION: Mitral valve replacement candidates had more
      baseline risk factors and higher raw rates of postoperative mortality and
      morbidity, which did not reach statistical significance.

PMID- 24585290
TI  - Thoracic melioidosis: a diagnostic dilemma.
AB  - The diagnosis of melioidosis can be difficult, and it is frequently described as
      "the great mimicker". We report a case of thoracic melioidosis presenting as a
      mediastinal mass with impending superior vena cava obstruction. With the
      presumptive diagnosis of mediastinal tumor, the patient underwent surgery for
      tissue sampling, and a purulent collection was found. The clinical syndromes of
      melioidosis and the diagnostic dilemma are discussed. 

PMID- 24585291
TI  - Pneumonectomy for nonmalignant disease.
AB  - BACKGROUND: Pneumonectomy for nonmalignant disease is unusual. We wondered about
      the incidence, predisposing risks, and outcomes of this entity. METHODS: We
      interrogated the Society of Thoracic Surgeons General Thoracic Surgery Database
      to compare patients undergoing pneumonectomy for benign or malignant indications
      between 2006 and 2010. RESULTS: 309 of 3081 (10%) patients underwent
      pneumonectomy for nonmalignant conditions. The benign group were younger (56 vs.
      62 years), more likely to be on steroid therapy (11.3% vs. 2.7%), and less likely
      to be current smokers (14.4% vs. 20.1%). Both groups had an equal incidence of
      comorbidities. Preoperative pulmonary function was decreased in the nonmalignant
      group: forced expiratory volume in 1 s 61% vs. 74% of predicted; carbon monoxide
      diffusion in the lung 61% vs. 71% of predicted. The most common nonmalignant
      etiologies requiring pneumonectomy were lung and pleural infections. The benign
      group had increased postoperative bleeding, infections, and lung-related
      complications. CONCLUSIONS: Approximately 10% of patients undergoing
      pneumonectomy have nonmalignant disease. In these cases, careful patient
      selection with detailed preoperative preparation including improvement in
      nutrition and functional status are indicated. Technical aspects of
      pneumonectomy, which minimize perioperative bleeding and infectious
      complications, are particularly important when this surgery is performed for
      nonmalignant conditions.

PMID- 24585292
TI  - Multiple coronary fistulae to left ventricle, with acute myocardial infarction.
AB  - A rare case of myocardial infarction secondary to multiple coronary artery
      fistulae is described. Coronary angiography showed the fistulae originating from
      the distal septal branch of the left anterior descending artery and distal
      branches of the right coronary and circumflex arteries, and drained into the left
      ventricle. A myocardial perfusion scan showed a fixed perfusion defect. 

PMID- 24585293
TI  - Chronic contained rupture of aortic aneurysm with thoracic vertebral erosion.
AB  - A 66-year-old man was transferred to our hospital with the diagnosis of a large
      thoracoabdominal aneurysm. Computed tomography showed thoracic vertebral erosion,
      suggesting a chronic contained rupture. He was hemodynamically stable with no
      neurological complication preoperatively. He underwent successful surgical
      replacement of the descending aorta. During surgery, the 6th and 7th thoracic
      vertebral bones adjacent to the thoracic aneurysm were found to be eroded. The
      postoperative course was uneventful. 

PMID- 24585295
TI  - Dedifferentiated chondrosarcoma: an aggressive variant of chondrosarcoma.
AB  - Dedifferentiated chondrosarcomas are a rare and aggressive subtype of
      chondrosarcoma with a bimorphic pattern on histopathology. Rib is a rare site of
      dedifferentiated chondrosarcoma. Diagnosis of this subtype preoperatively can be
      challenging. Treatment options for dedifferentiated chondrosarcoma are limited
      because they are chemoresistant, and therefore adequate surgery forms the main
      stay of treatment. We present our experience with a dedifferentiated
      chondrosarcoma of the rib, and discuss the management of this rare entity. 

PMID- 24585296
TI  - A rare image of myocardial bridging in right coronary artery territory.

PMID- 24585294
TI  - Virchow's triad and intestinal ischemia post cardiac surgery.
AB  - BACKGROUND: Intestinal ischemia is associated with a very high mortality rate. We
      combined the principles of Virchow's triad to produce preoperative and
      postoperative models for the development of intestinal ischemia. METHODS: A
      single institutional study was undertaken involving 18,325 consecutive patients
      from April 1997 to March 2012. Univariate and multivariate analysis was
      performed. RESULTS: Mortality was 87% in 91 patients who developed bowel
      ischemia. Multivariate logistic regression demonstrated that age, peripheral
      vascular disease, intraaortic balloon pump support, female sex, and preexisting
      renal failure were significant determinates of intestinal ischemia
      preoperatively. Logistic regression demonstrated that age, peripheral vascular
      disease, creatine kinase-MB level, reoperation for bleeding, and blood product
      usage were significant determinates of intestinal ischemia postoperatively.
      CONCLUSIONS: Potentially remedial causes of intestinal ischemia include blood
      product usage, reoperation for bleeding, and creatine kinase-MB release. Age,
      female sex, peripheral vascular disease, intraaortic balloon pump usage, and
      preexisting renal failure are fixed risk factors. Despite the continuing trend of
      reduced blood product usage in the field of cardiac surgery, the increase in
      patients' risk factors will mean that incidences of intestinal ischemia may
      increase in the future.

PMID- 24585297
TI  - Chondrosarcoma of the chest wall: single-center experience.
AB  - BACKGROUND: chondrosarcoma is the most common primary tumor of the chest wall. We
      analyzed cases of chest wall chondrosarcoma to establish the presentation,
      diagnostic tools, surgical treatment, and outcome. METHODS: this was a
      retrospective observational analysis of 45 patients who underwent surgery for
      chondrosarcoma. RESULTS: the mean age was 42.3 +/- 8.5 years, and 57.8% patients
      were male. Symptoms were a painful chest wall mass in 91.1% of patients. Chest
      radiography and computed tomography, and biopsy were the diagnostic tools. The
      tumor was right-sided in 57.8% of patients. It was located in the lateral
      (71.1%), anterior (26.7%), or posterior (2.2%) chest wall. The mean tumor
      diameter was 7.6 +/- 3.3 cm. Radical en-bloc excision was performed in all
      patients. Chest wall reconstruction was carried out using methylmethacrylate and
      Prolene mesh (42.2%), Prolene mesh alone (37.8%), and direct closure (20%). A
      muscle flap was used for soft tissue reconstruction in 11.1%. Complications were
      encountered in 6.7%. There was no operative mortality. Follow-up was complete in
      66.7% of patients. The mean follow-up period was 3.7 +/- 2.1 years. Local
      recurrences and late mortality occurred in 4.4%. CONCLUSION: surgery for
      chondrosarcoma can be performed with acceptable morbidity and mortality. Proper
      selection of patients and radical en-block excision of the tumor are the keys for
      successful treatment and better outcomes.

PMID- 24585298
TI  - Pryce type I sequestration: no mosquito shooting.
AB  - We report a case of a 40-year-old woman with congenital dual arterial supply to
      an otherwise normal left lower lobe, causing hyperperfusion lung injury. In
      addition to near normal pulmonary arterial supply, the lower lobe of the left
      lung received a systemic arterial supply from the descending thoracic aorta. The
      patient was successfully managed by surgical ligation of the systemic arterial
      supply without lobectomy. We discuss when to defer lobectomy in Pryce type I
      sequestration. 

PMID- 24585299
TI  - Partial aortic root replacement for aneurysm of the right sinus of Valsalva.
AB  - An aneurysm of the sinus of Valsalva is clinically rare, and its operative
      indications and procedures are controversial. We herein report the rare case of a
      68-year-old woman with severe right ventricular outflow tract obstruction caused
      by an aneurysm of the right sinus of Valsalva. We performed partial aortic root
      reconstruction using a bovine pericardial patch, and aortic valve replacement.
      Although this case provides evidence that these are suitable surgical techniques
      for treatment of aneurysm of the sinus of Valsalva, total aortic root replacement
      should have been chosen based on the pathological finding of aortic medial and
      valve degeneration. 

PMID- 24585300
TI  - A novel approach in managing right-sided haemothorax in neurofibromatosis type 1.
AB  - Spontaneous haemothorax due to vasculopathy in patients with neurofibromatosis
      type 1 is rare but life-threatening. A 56-year-old lady with neurofibromatosis
      type 1 presented with right-sided chest pain, dyspnoea, and collapse. Computed
      tomography showed a right-sided hemothorax. Urgent angiography showed contrast
      leakage from a right subclavian artery pseudoaneurysm. A Gore Viabahn
      endovascular stent graft was deployed. Completion angiography revealed
      satisfactory haemostasis. She underwent video-assisted thoracoscopic evacuation
      of the hemothorax, with good results. This case highlights a novel approach to
      managing a rare emergency, using combined procedures. 

PMID- 24585301
TI  - Dissecting intramural hematoma of esophagus after thrombolytic therapy: a case
      report.
AB  - Esophageal hematoma is a relatively rare event. We report a case of severe chest
      pain associated with myocardial infarction and recurrent chest pain after
      administration of a thrombolytic agent. The chest pain was different from the
      presenting symptom and accompanied by 2 episodes of hematemesis. Esophageal
      hematoma was confirmed after endoscopy and computed tomography. Esophageal
      hematoma is a relatively rare event after thrombolytic therapy. 

PMID- 24585302
TI  - Chest wall malignant peripheral nerve sheath tumor in a 21-year old female.
AB  - Malignant peripheral nerve sheath tumors are aggressive sarcomas that derive from
      peripheral nerve cells and are associated with a poor prognosis. We report a rare
      case of malignant peripheral nerve sheath tumor in the anterior chest wall of a
      21-year-old female. The patient underwent induction chemotherapy, and resection
      of the mass with negative margins. She subsequently underwent radiation therapy. 

PMID- 24585303
TI  - Nanofiber-reinforced myocardial tissue-construct as ventricular assist device.
AB  - OBJECTIVES: This study aimed to create a myocardial tissue construct by tissue
      engineering to repair, replace, and regenerate damaged cardiac tissue. METHODS
      AND RESULTS: Human cardiac muscles harvested from a homograft heart retrieval
      system were decellularized followed by coating with electrospun nanofibers to
      make them amenable to scaffolding. These processed cardiac tissues were nourished
      in modified media having ischemic cardiac tissue conditioned media in 6 separate
      experimental variants, and cord blood mononuclear cells were injected into 4 of
      them. On the 17th day of culture, the nanofiber-coated scaffolds injected with
      mononuclear cells and/or reinforced by electrical and mechanical forces, started
      contracting spontaneously at varying rates, while the control remain
      noncontractile. Histological staining confirmed the pre-culture acellularity as
      well as post-culture stem cell viability, and revealed expression of troponin I
      and cardiac myosin. The acellular processed scaffold when implanted into sheep
      ischemic myocardial apex revealed transformation into sheep myocardium after 4
      months of implantation. CONCLUSION: These results provide direct evidence for the
      re-cellularization of decellularized cardiac tissue grafts reinforced with a
      polymer nanofiber coating, by human mononuclear cells injection, leading to
      generation of a tissue-engineered myocardial construct.

PMID- 24585304
TI  - Internal thoracic artery: anatomical and biological characteristics revisited.
AB  - The left internal thoracic artery has become the conduit of choice for coronary
      artery bypass grafting, due to its superior patency rates at 10 or more years
      with little or no evidence of atherosclerotic changes. Recent evidence indicates
      that a second internal thoracic artery graft provides improved results relative
      to overall survival and major cardiac and cerebrovascular event-free survival,
      and reduces the need for repeat revascularization. However, the routine use of
      bilateral internal thoracic arteries is limited due to a perceived higher
      incidence of deep sternal wound infection. The surgical anatomy, collateral blood
      supply to the sternum, and biological characteristics of internal thoracic artery
      conduits are reviewed. 

PMID- 24585305
TI  - Continuity of care by cardiothoracic nurse practitioners: impact on outcome.
AB  - OBJECTIVES: There have been recent reports on increased mortality in British
      National Health Service hospitals during weekends. This study aimed to assess the
      impact on patient care following the introduction of nurse practitioner cover for
      the cardiothoracic ward, including weekends. METHODS: Prospectively collected and
      validated data of patients operated on from January 2005 to October 2011 were
      analyzed. The patients were grouped according to era: before (n = 2385) and after
      (n = 3910) the introduction of nurse practitioners in October 2007. RESULTS:
      There were no significant differences in preoperative patient characteristics
      such as age, logistic EuroSCORE, sex, smoking, and extracardiac vascular
      problems. There were more patients from an Asian background (p < 0.01), more with
      noninsulin-dependent diabetes (p < 0.01), and more requiring urgent cardiac
      surgery (p < 0.01) in the later era. Following the introduction of nurse
      practitioner grade, there was a decrease in the rate of cardiac intensive care
      unit readmission from 2.6% to 1.9% (p = 0.05) and length of hospital stay from 10
      to 8 days (p < 0.01). There was a significant improvement in overall survival
      after cardiac surgery from 96.5% to 98.0% (p < 0.01). Logistic regression
      analysis confirmed that the presence of nurse practitioners on the ward was the
      strongest predictor of survival with an odds ratio of 1.9 (95% confidence
      interval: 1.23-3.01). CONCLUSION: The introduction of the nurse practitioner
      grade to provide continuity in patient care including at weekends has been
      confirmed to improve patient outcomes including survival after cardiac surgery.

PMID- 24585306
TI  - Which is the best graft for the right coronary artery?
AB  - Bilateral internal mammary arteries directed to the left coronaries are gaining
      popularity; an increasing level of evidence nowadays supports this surgical
      strategy. On the other hand, composite right internal mammary artery, radial
      artery, and gastroepiploic artery targeting high-grade stenotic lesions in the
      right coronary artery system may confer improved mid- and long-term patency
      compared to long saphenous veins. This analysis looks into the evidence comparing
      data of the third best available conduit for grafting the right coronary artery,
      and by extrapolating this report, compares total arterial revascularization vs.
      conventional coronary artery bypass grafting. 

PMID- 24585307
TI  - Innominate artery injury from disseminated tuberculosis.
AB  - A 49-year-old man presented with chest pain and was found to have hemorrhage and
      drainage from a chest wound secondary to disseminated tuberculosis involving the
      sternum and ankle. He then developed acute hemorrhage from an innominate artery
      pseudoaneurysm originating just below a severely diseased sternoclavicular
      junction. A staged approach was used to manage his pathology given the life
      threatening bleeding and his debilitated condition. He underwent endovascular
      stent grafting to exclude the pseudoaneurysm, followed by aggressive debridement
      of the affected sternal area. 

PMID- 24585308
TI  - Cystic hamartoma of the posterior mediastinum.

PMID- 24585309
TI  - Isolated left main coronary ostial stenosis.

PMID- 24585310
TI  - Aortic valve replacement in single coronary artery with tortuous left main trunk.

PMID- 24585311
TI  - Intrathymic epidermoid cyst: a very rare condition.
AB  - A 65-year-old man presented with a nonspecific thymic neoplasm following blunt
      thoracic trauma. The lesion increased in size over 12 years, to reach 47 mm in
      diameter. After thymectomy, the lesion was described as an epidermoid lining cyst
      composed of thickened stratified squamous epithelium. We assume that this rare
      pathological condition was caused by skin tissue islands and fat migrating into
      the mediastinum. 

PMID- 24585312
TI  - Chest tube in transected left main bronchus after blunt chest trauma.

PMID- 24585313
TI  - Redo mitral valve replacement using the valve-on-valve method.
AB  - Despite improvements in bioprosthetic valve function, increased human life
      expectancy has led to a growing number of bioprosthetic valve deterioration cases
      requiring reoperation. We report 2 cases of primary tissue failure of a
      bioprosthetic valve, which were treated by mitral valve replacement using the
      valve-on-valve method. The reasons for the reoperations were a severely calcified
      valve annulus, and severe adhesion of a previous bioprosthetic valve. We removed
      only the leaflets of the bioprosthetic valve and sutured a Carbomedics OptiForm
      valve onto the sewing cuff of the previous bioprosthesis. No complications,
      including major cardiac events, were noted during the follow-up.

PMID- 24585314
TI  - A case of primary effusion lymphoma diagnosed by open cardiocentesis.
AB  - Primary effusion lymphoma is a type of B-cell lymphoma that is primarily related
      to human immunodeficiency virus. Thoracic surgeons rarely encounter this disease
      because of its rarity. We herein report a case of primary effusion lymphoma which
      required surgery for successful treatment. An 83-year-old man was admitted to our
      hospital with signs of cardiac tamponade. A radiological examination revealed a
      pericardial effusion. Performing percutaneous pericardiocentesis was difficult
      due to the patient's anatomical features. We performed open cardiocentesis under
      general anesthesia. A cytologic examination revealed primary effusion lymphoma.
      The patient underwent chemotherapy, resulting in complete remission.

PMID- 24585315
TI  - Elevated hemoglobin A1c is associated with readmission but not complications.

PMID- 24585316
TI  - Large diaphragmatic hernia due to omental transfer for sternal wound infection.

PMID- 24585317
TI  - Response to: Elevated hemoglobin A1c is associated with readmission but not
      complications.

PMID- 24585318
TI  - Primary cardiac synovial sarcoma.
AB  - Approximately 10% of soft tissue sarcomas are synovial sarcomas, and 90% of these
      occur in the extremities. Among the primary tumors in the heart, 25% are
      malignant. Primary synovial sarcoma of the heart is an extremely rare entity. A
      myriad of investigations such as histopathology, immunohistochemistry, electron
      microscopy, and molecular genetic techniques are required for confirmation of the
      diagnosis. The tumor is nearly always lethal, but surgical resection with
      chemotherapy may prolong the life of the patient. We describe the case of a young
      patient with a primary synovial sarcoma arising from the right ventricle. 

PMID- 24585319
TI  - Neonatal repair of total anomalous pulmonary venous connection and lung agenesis.
AB  - Here we report a neonatal case of total anomalous pulmonary venous connection
      with left lung agenesis. Diagnostic imaging demonstrated that the left pulmonary
      veins were totally absent and the right pulmonary veins connected with the common
      pulmonary chamber. Drainage from the common pulmonary venous chamber entered the
      persistent left suerior vena cava. In addition, it revealed complete absence of
      the left main bronchus and left lung vessels. The neonate successfully underwent
      surgical repair 18 days after birth.

PMID- 24585320
TI  - Prophylaxis for acute exacerbation of interstitial pneumonia after lung
      resection.
AB  - BACKGROUND AND PURPOSE: Acute exacerbation of interstitial pneumonia is a life
      threatening complication after lung cancer surgery. Dorsal subpleural fibrotic
      changes occupying 3 or more segments of both lower lobes on high-resolution
      computed tomography indicate a very high risk. We conducted a prospective phase
      II study to assess the efficacy of prophylactic treatment. METHODS: Patients with
      lung cancer underwent high-resolution computed tomography preoperatively to
      assess the risk of acute exacerbations of interstitial pneumonia. Before
      induction of general anesthesia, high-risk patients received 125 mg of
      methylprednisolone as an intravenous bolus and sivelestat sodium hydrate 300 mg
      .day(-1) as a continuous intravenous infusion. From January 2010 through August
      2011, a total of 327 patients underwent surgery for lung cancer, and 31 (9.5%)
      were enrolled. RESULTS: There was no case of acute exacerbation. No adverse
      events were associated with prophylaxis. Usual interstitial pneumonia was
      confirmed histopathologically in 25 (80.6%) patients. Four (12.9%) patients had
      major complications. Usual interstitial pneumonia was diagnosed postoperatively
      in 4 (1.4%) of 327 patients who did not meet the inclusion criteria, and 1 of
      these patients died due to acute exacerbation of occult interstitial pneumonia.
      CONCLUSION: Perioperative use of sivelestat sodium hydrate and low-dose
      methylprednisolone may be useful as prophylaxis for acute exacerbation of
      interstitial pneumonia.

PMID- 24585321
TI  - Transverse coronoid fracture: when does it have to be fixed?
AB  - BACKGROUND: After elbow fracture-dislocation, surgeons confront numerous
      treatment options in pursuing a stable joint for early motion. The relative
      contributions of the radial head and coronoid, in combination, to elbow stability
      have not been defined fully. QUESTIONS/PURPOSES: The purpose of this study was to
      evaluate the effect of an approximately 50% transverse coronoid fracture and
      fixation in the setting of an intact or resected radial head on coronal
      (varus/valgus) and axial (internal and external rotational) laxity in (1) gravity
      varus stress; and (2) gravity valgus stress models. METHODS: Kinematic data were
      collected on six fresh-frozen cadaveric upper extremities tested with passive
      motion throughout the flexion arc under varus and valgus gravity stress with
      lateral collateral ligaments reconstructed. Testing included coronoid fracture
      and osteosynthesis with and without a radial head. RESULTS: In the varus gravity
      stress model, fixation of the coronoid improved varus stability (fixed: 1.6
      degrees  [95% confidence interval, 1.0-2.2], fractured: 5.6 degrees  [4.2-7.0], p
      < 0.001) and internal rotational stability (fixed: 1.8 degrees  [0.9-2.7],
      fractured: 5.4 degrees  [4.0-6.8], p < 0.001), but radial head fixation did not
      contribute to varus stability (intact head: 2.7 degrees  [1.3-4.1], resected
      head: 3.8 degrees  [2.3-5.3], p = 0.4) or rotational stability (intact: 2.7
      degrees  [0.9-4.5], resected head: 3.9 degrees  [1.5-6.3], p = 0.4). With valgus
      stress, coronoid fixation improved valgus stability (fixed: 2.1 degrees  [1.0
      3.1], fractured: 3.8 degrees  [1.8-5.8], p < 0.04) and external rotation
      stability (fixed: 0.8 degrees  [0.1-1.5], fractured: 2.1 degrees  [0.9-3.4], p <
      0.04), but the radial head played a more important role in providing valgus
      stability (intact: 1.4 degrees  [0.8-2.0], resected head: 7.1 degrees  [3.5
      10.7], p < 0.001). CONCLUSIONS: Fixation of a 50% transverse coronoid fracture
      improves varus and internal rotatory laxity but is unlikely to meaningfully
      improve valgus or external rotation laxity. The radial head, on the other hand,
      is a stabilizer to resist valgus stress regardless of the status of the coronoid.
      CLINICAL RELEVANCE: Determination as to whether it is necessary to fix a coronoid
      fracture should be based on the stability of the elbow when tested with a varus
      load. The elbow may potentially be stable with fractures involving less than 50%
      of the coronoid. Under all circumstances, the radial head should be fixed or
      replaced to ensure valgus external rotatory stability.

PMID- 24585322
TI  - Open reduction and internal fixation of radial head fractures: do outcomes differ
      between simple and complex injuries?
AB  - BACKGROUND: Radial head fractures can occur in isolation or in association with
      elbow and forearm injuries. Treatment options include nonoperative management,
      fragment or whole-head excision, open reduction and internal fixation (ORIF), and
      radial head arthroplasty. However, the evidence supporting ORIF for repairable
      radial head fractures is inconclusive. QUESTIONS/PURPOSES: We compared patients
      undergoing ORIF for isolated radial head fractures or for radial head fractures
      associated with other fractures or elbow dislocations in terms of patient-related
      disability, presence of posttraumatic arthritis, complications, and rate of
      reoperation for capsular release. METHODS: Between 1997 and 2008, 52 patients
      underwent ORIF of the radial head for isolated radial head fractures (simple
      group) and 29 underwent ORIF for radial head fracture with an associated fracture
      or dislocation (complex group). General indications for ORIF included displaced
      radial fractures, large articular surface fragments, and greater than 2 mm of
      displacement and/or a mechanical block to forearm rotation or associated
      fractures or ligament injuries requiring surgery. Thirty-one patients (60%) in
      the simple group and 20 (69%) in the complex group were available for followup at
      a mean of 4 years (range, 1.0-9.5 years). We evaluated the patients using a
      validated self-reported pain and disability questionnaire (Patient-rated Elbow
      Evaluation [PREE]). Records review included radiographic examination and
      assessment of major complications and secondary surgery rates for capsular
      release. RESULTS: With the numbers available, the groups were not different in
      terms of the mean PREE scores (8 versus 15 for the simple and complex groups,
      respectively; p = 0.13, lower values indicate lower pain and disability). The
      simple and complex groups were also not different with the numbers available in
      terms of major complications (13% versus 25%, respectively; p = 0.29) or
      secondary capsular release (3% versus 20%, respectively; p = 0.07). CONCLUSIONS:
      At short term, we found no differences between patients treated with ORIF for
      isolated radial head fractures and those treated for radial head fractures in
      association with other elbow injuries with regard to pain and disability scores;
      loss to followup in this series precludes making statements with great confidence
      about function after these injuries. However, the substantial capsular release
      and complication rates should weigh into the preoperative discussion with
      patients before selecting ORIF for radial head fractures. LEVEL OF EVIDENCE:
      Level III, therapeutic study. See Instructions for Authors for a complete
      description of levels of evidence.

PMID- 24585323
TI  - Bilateral transfemoral/transtibial amputations due to battle injuries: a
      comparison of Vietnam veterans with Iraq and Afghanistan servicemembers.
AB  - BACKGROUND: Multiple limb loss from combat injuries has increased as a proportion
      of all combat-wounded amputees. Bilateral lower-extremity limb loss is the most
      common, with bilateral transfemoral amputations being the most common subgroup
      followed by bilateral amputations consisting of a single transfemoral amputation
      and a single transtibial amputation (TFTT). With improvements in rehabilitation
      and prostheses, we believe it is important to ascertain how TFTT amputees from
      the present conflicts compare to those from the Vietnam War. QUESTIONS/PURPOSES:
      We compared self-reported (1) health status, (2) quality of life (QoL), (3)
      prosthetic use, and (4) function level between TFTT amputees from the Vietnam War
      and Operation Iraqi Freedom/Operation Enduring Freedom (OIF/OEF). METHODS: As
      part of a larger survey, during 2007 to 2008, servicemembers with a diagnosis of
      amputation associated with battlefield injuries from the Vietnam War and OIF/OEF
      were identified from the Veterans Affairs and military databases. Participants
      were asked to respond to a questionnaire to determine their injuries, surgical
      history, presence of other medical problems, health status, QoL, function, and
      prosthetic use. We assessed QoL and health status using single-item questions and
      function using seven categories of physical activity. Thirteen of 298 (4.3%)
      participants in the Vietnam War group and 11 of 283 (3.8%) in the OIF/OEF group
      had sustained TFTT amputations. Mean age +/- SD at followup was 61 +/- 2 years
      and 28 +/- 5 years for the Vietnam War and OIF/OEF groups, respectively. RESULTS:
      Excellent, very good, and good self-reported health (85% versus 82%; p = 0.85)
      and QoL (69% versus 72%; p = 0.85) were similar between the Vietnam War and
      OIF/OEF groups, respectively. Level of function was higher in the OIF/OEF group,
      with four of 11 reporting participation in high-impact activities compared to
      none in the Vietnam War group (p = 0.018). CONCLUSIONS: Participants with TFTT
      limb loss from both conflicts reported similar scores for QoL and health status,
      although those from OIF/OEF reported better function and use of prosthetic
      devices. It is unclear whether the improved function is from age-related changes
      or improvements in rehabilitation and prosthetics. Some areas of future research
      might include longitudinal studies of those with limb loss and assessments of
      physical function of older individuals with limb loss as the demographics shift
      to where this group of individuals becomes more prominent.

PMID- 24585324
TI  - Evaluation of three types of passive samplers for measuring 1,3-butadiene and
      benzene at workplaces.
AB  - 1,3-Butadiene and benzene are common pollutants in both workplace and ambient air
      and have received attention for their adverse effects on human health. In
      exposure studies, simple and sensitive personal monitoring methods are
      preferable. Thermal desorption passive samplers seem optimal for this purpose,
      although in occupational studies chemical desorption samplers have been used more
      often. This may be because their utility for monitoring occupational atmospheres
      has not been thoroughly validated. Therefore, we evaluated thermal desorption
      passive samplers containing Carbopack X adsorbent from three manufacturers:
      Perkin Elmer, SKC-Ultra and Radiello. The uptake rates of benzene and 1,3
      butadiene by these samplers were determined over 4 h or 8 h in exposure chamber
      studies at three concentrations likely to be found in occupational air. The
      samplers were also tested in a field study, at a petroleum refinery. The results
      were analyzed using multiple linear regression, and intra-class correlation
      coefficients (ICCs) were calculated to compare uptake rates of the three passive
      samplers to those of an active sampler. The three samplers had similar and
      acceptable accuracy (ICC>=0.9) for measuring benzene concentrations in the field
      environments, but only the Perkin Elmer sampler gave acceptable ICC values
      (~0.85) for 1,3-butadiene over a full 8 h working shift in the field test. The
      results indicate that passive thermal desorption monitors can provide
      considerably lower limits of detection than chemical desorption monitors after 4
      8 h sampling time, even down to environmental background concentrations, enabling
      comparison with measurements in ambient air.

PMID- 24585325
TI  - Alternative Intensive Therapy for PTSD.

PMID- 24585326
TI  - Treatment of psychosis and risk assessment for violence.

PMID- 24585327
TI  - Increasing treatment engagement for persons with serious mental illness using
      personal health records.

PMID- 24585328
TI  - A word to the wise about ketamine.

PMID- 24585329
TI  - Behavioral and psychiatric symptoms in prion disease.
AB  - The prion diseases are rare neurodegenerative conditions that cause complex and
      highly variable neuropsychiatric syndromes, often with remarkably rapid
      progression. Prominent behavioral and psychiatric symptoms have been recognized
      since these diseases were first described. While research on such symptoms in
      common dementias has led to major changes in the way these symptoms are managed,
      evidence to guide the care of patients with prion disease is scarce. The authors
      review the published research and draw on more than 10 years' experience at the
      U.K. National Prion Clinic, including two large prospective clinical research
      studies in which more than 300 patients with prion disease have been followed up
      from diagnosis to death, with detailed observational data gathered on
      symptomatology and symptomatic treatments. The authors group behavioral and
      psychiatric symptoms into psychotic features, agitated features, and mood
      disorder and describe their natural history, showing that they spontaneously
      improve or resolve in many patients and are short-lived in many others because of
      rapid progression of global neurological disability. Diagnostic category, disease
      severity, age, gender, and genetic variation are or may be predictive factors.
      The authors review the observational data on pharmacological treatment of these
      symptoms in the U.K. clinical studies and make cautious recommendations for
      clinical practice. While nonpharmacological measures should be the first-line
      interventions for these symptoms, the authors conclude that there is a role for
      judicious use of pharmacological agents in some patients: antipsychotics for
      severe psychosis or agitation; benzodiazepines, particularly in the late stages
      of disease; and antidepressants for mood disorder. 

PMID- 24585330
TI  - When affective disorders were considered to emanate from the heart: the Ebers
      papyrus.

PMID- 24585331
TI  - Developmental lag and course of cognitive deficits from the premorbid to
      postonset period in schizophrenia.

PMID- 24585332
TI  - Response to Bora.

PMID- 24585333
TI  - Management issues during pregnancy in women with bipolar disorder.

PMID- 24585334
TI  - Response to Sharma and Sommerdyk.

PMID- 24585342
TI  - Factors related to employers' intent to hire, retain and accommodate cancer
      survivors: the Singapore perspective.
AB  - PURPOSE: Despite the growing importance of cancer and return-to-work issues in
      occupational rehabilitation literature in the last decade, academic discussion is
      largely limited to survivors' perspectives and some exploratory studies from the
      employer side. This paper applies two classic theoretical models-Theory of
      Planned Behavior and Social Cognitive Theory-and key measures from previous
      studies to identify explicit relationships that explain employer factors to hire
      and retain cancer survivors. METHODS: Data were collected from online surveys
      with senior management executives and senior human resource specialists from
      various organizations in Singapore, with a total of 145 responses. The 72-item
      survey instrument included a series of independent variables: (1) Attitudes
      toward cancer and cancer survivors; (2) Employers' efficacy; (3) Perceived moral
      obligation; (4) Employers' experience; (5) Outcome expectations; (6) Employment
      situation; (7) Social norms; and (8) Incentives, and dependent variables: (a)
      Employers' intention to hire cancer survivors; and (b) Employers' intention to
      retain cancer survivors. RESULTS: Regression analyses showed that the top three
      factors related to employers' intention to retain cancer survivors are perceived
      moral obligations (beta = .39, p < .001), followed by attitudes toward cancer
      (beta = .25, p < .01), and employment situation (beta = .17, p < .05). Employers'
      efficacy was associated with intention to hire (beta = .22, p < .05), coupled
      with attitude toward cancer survivors (beta = .22, p < .01). The findings also
      indicated the important role of existing relationship between an employer and an
      employee when it comes to retaining cancer survivors and government incentives
      for hiring cancer survivors in the workforce. CONCLUSIONS: The present study
      provided an avenue to implement the proposed model-a potential study framework
      for the management of cancer survivors at work. Findings revealed that different
      messages should be tailored to employers toward hiring and retention issues and
      provided useful guidelines for employer education materials.

PMID- 24585343
TI  - Effects of nutrition level of concentrate-based diets on growth performance and
      carcass characteristics of Hainan black goats.
AB  - This study assessed the effects of different nutrition levels of diets on growth
      performance and carcass characteristics of Hainan black goat. Twenty-four goats
      were divided into six diet treatments, which consisted of two levels of crude
      protein (CP; 15 and 17 %) and three levels of digestive energy (DE; 11.72, 12.55,
      and 13.39 MJ/kg). The results revealed that 17 % CP significantly (P < 0.05)
      increased ADG and improved FCR compared with 15 % CP. Therefore, the CP levels of
      diet affected growth performance. CP and DE levels in the diet had no significant
      effects (P > 0.05) on carcass characteristics of the goats. The mRNA expression
      levels of insulin-like growth factor 1 in muscle tissues increased with
      increasing CP and DE levels (P < 0.05). 

PMID- 24585344
TI  - Effect of axial length reduction after trabeculectomy on the development of
      hypotony maculopathy.
AB  - PURPOSE: To measure changes in axial length before and after trabeculectomy with
      noncontact, partial coherence laser interferometry and identify patient factors
      that lead to the development of hypotony maculopathy and axial length shortening
      in 25 eyes with intraocular pressure (IOP) <= 6 mmHg at 4 weeks after mitomycin C
      augmented trabeculectomy. METHODS: A retrospective comparative case series.
      Hypotony maculopathy was identified with both ophthalmoscopy and spectral-domain
      optical coherence tomography. Axial length and IOP were serially measured pre-
      and postoperatively. Logistic regression analysis was performed to identify
      factors associated with the presence of hypotony maculopathy at 4 weeks after
      trabeculectomy and multiple regression analysis to identify factors associated
      with axial length changes. RESULTS: Ten eyes exhibited hypotony maculopathy,
      whereas the remaining 15 did not. Patients with hypotony maculopathy were
      significantly younger (47.7 +/- 6.2 years) compared with those without it (63.3
      +/- 9.6 years, P = 0.0002, unpaired t test). The percent reduction of axial
      length after trabeculectomy was significantly larger in the former group (5.91 +/
      2.76 %) compared with the latter group (1.51 +/- 0.91 %) (P = 0.0001, Mann
      Whitney U test). Multivariate analyses showed that only age was associated with
      the presence of hypotony maculopathy, with an odds ratio of 0.82 (P = 0.0075),
      when age, sex, type of glaucoma, lens status, percent changes in axial length and
      IOP before and after trabeculectomy, and central corneal thickness were included
      as independent variables (R (2) = 0.543, P = 0.003). CONCLUSIONS: Age-dependent
      axial length reduction is a risk factor for the development of hypotony
      maculopathy after trabeculectomy.

PMID- 24585345
TI  - Idiopathic left ventricular apical hypoplasia.
AB  - A 46-year-old man was found to have an abnormal ECG taken during a routine health
      and blood pressure check. His only symptom was non-specific central chest
      discomfort, unrelated to exertion. His ECG showed sinus rhythm, a normal axis and
      poor R wave progression across the chest leads and lateral T wave flattening. An
      echocardiogram showed a dilated left ventricle with a thin and hypokinetic septum
      bulging to the right. The apex was 'not well seen' but also appeared thin and
      hypokinetic. The right heart and valves were normal. The patient was further
      investigated for left ventricular hypoplasia. 

PMID- 24585346
TI  - Somatic and mental health service use of children and adolescents in Germany
      (KiGGS-study).
AB  - Only a limited number of national surveys have investigated both somatic and
      mental health service use in children and adolescents. The current study aimed to
      assess service use in Germany as based on at least a single contact with a
      somatic (pediatrician, general practitioner, nonmedical practitioner) and/or
      mental health (psychiatrist, psychologist, youth welfare) care specialist within
      the last 12 months. Questionnaire responses of 6,475 children and adolescents
      aged 11.0-17.9 years and their parents were analyzed based on data ascertained by
      the German Child and Adolescent Health Survey (KiGGS) conducted between 2003 and
      2006. For assessment of mental symptom loading the Strengths and Difficulties
      Questionnaire (SDQ) was completed by parents, thus allowing the determination of
      the relationship between symptom loading and service use. ANOVA and logistic
      regression were performed to determine help-seeking behavior overall and of
      different health professional groups upon inclusion of the SDQ Total Difficulties
      score, gender, age and socio-economic status (SES). A total of 81.9 % of all
      children and adolescents had used any kind of service within the past 12 months.
      Seventy-seven percent and 0.8 % used only the somatic and mental health services,
      respectively; 4.1 % had frequented both services. Amongst youths with a
      'borderline' and 'abnormal' Total Difficulties score, 11.8 and 18.6 %,
      respectively, sought help from mental health partners. Age, SES and Total
      Difficulties score were predictors of any service use; the logistic regression
      model explained 7.6 % of the variance. Use of mental health service was
      significantly predicted by only age and Total Difficulties score, the respective
      model explained 26.2 % of the variance. The comparison of health services use on
      an international level is rendered difficult by national differences in health
      care provision. Nevertheless, several of our findings are similar to results
      obtained in other nationally representative surveys.

PMID- 24585347
TI  - [Primary renal rhabdomyosarcoma: a case report].
AB  - Renal sarcoma represents 1-3% of all renal malignant tumours. Primary
      rhabdomyosarcoma of the kidney is a rare and highly aggressive tumor in the adult
      population. Here, we report the case of a 50-year-old woman with a large
      rhabdomyosarcoma of the left kidney and associated adrenal cortical adenoma.
      Rhabdomyo sarcoma is a very rare tumor in adults but it needs to be considered in
      the differential diagnosis among undifferentiated malignant tumors.

PMID- 24585348
TI  - Oral focal epithelial hyperplasia: report of three cases.
AB  - Focal epithelial hyperplasia or Heck's disease is an infrequent asymptomatic
      condition caused by human papillomavirus types 13 or 32 affecting the mucous
      membrane of the mouth and is commonly seen in young individuals. Firstly, it was
      described in Indians and Eskimos, but it exists in various populations. We
      present three cases of Heck's disease in an Afghan immigrant family group living
      in Iran that seem to have familial predominance. The disease was identified as
      oral focal epithelial hyperplasia on the basis of histopathologic and clinical
      findings. The lesions were reduced significantly after 4 months of good oral
      hygiene. Dentists should be familiar with the clinical manifestations of these
      types of lesions that affect the oral cavity. In fact, histopathologic assessment
      and clinical observation are necessary to establish the diagnosis.

PMID- 24585349
TI  - Cytopathologic diagnosis of spontaneous infarction of fibroadenoma of the breast.
AB  - Infarction is an uncommon event in a fibroadenoma, which is the commonest benign
      tumor of the breast. Most often it occurs in pregnancy, lactation or is secondary
      to fine needle aspiration. Spontaneous infarction of a fibroadenoma in the
      absence of a predisposing condition is very rare. The cytopathologic features of
      infarction are necrosis and worrisome nuclear features, which are often
      misinterpreted as either inflammation or malignancy. We detail a report of
      accurate cytopathologic diagnosis of spontaneous infarction of fibroadenoma in a
      17-year-old adolescent non pregnant girl. Careful attention to the cytopathologic
      clues like uniform thickness of the necrotic epithelial fragments, branching
      pattern reminiscent of the staghorn pattern despite atypical nuclear features and
      clinical details like young age of the patient and recent onset pain in a pre
      existing lump helped arrive at the correct diagnosis and spared the patient of a
      radical excision. To the best of our knowledge, there are no earlier reports of
      correct cytopathologic diagnosis. 

PMID- 24585350
TI  - Incidentally Discovered Extensive Squamous Metaplasia within Borderline Phyllodes
      Tumor: Presentation of a Rare Tumor.
AB  - Phyllodes tumors are uncommon biphasic fibroepithelial neoplasms of breast,
      comprising less than 1% of all breast neoplasms. We therefore aimed to present
      the case with its microscopic findings. In this article, we report a 59-year-old
      female admitted to the general surgery department with a rapidly, enlarging,
      palpable mass in right breast. After histopathological examination, it was
      diagnosed as borderline phyllodes tumor with extensive squamous metaplasia.
      Metaplastic changes are infrequent in the stromal and epithelial component of
      these tumors. Extensive squamous metaplasia within phyllodes tumor is rare and
      may occur in benign, borderline and malign subtypes. 

PMID- 24585351
TI  - Placental polyp - a rare case report.
AB  - Placental polyp is the retained fragment of placental tissue after the
      parturition or abortion for indefinite period which forms a polypoidal mass in
      the uterus. It is predominantly composed of necrotic and hyalinized chorionic
      villi (ghost chorionic villi). We report a case of 26-year-old G2P2 woman
      presenting with vaginal bleeding. Her last pregnancy had occurred five years ago.
      Laboratory investigations revealed a positive urine pregnancy test and serum
      levels of beta-human chorionic gonadotrophin (beta-hCG) was elevated.
      Ultrasonography revealed hyperechoic mass in uterine cavity. She underwent total
      abdominal hysterectomy and the pathological diagnosis was of a placental polyp.

PMID- 24585354
TI  - Ovarian Yolk Sac Tumor with Granulomatous Reaction Resembling Tuberculosis - A
      Unique Presentation.
AB  - Yolk sac tumors (endodermal sinus tumors) are an important subgroup of germ cell
      tumors of the ovary. They are seen in young females and are highly aggressive,
      but respond well to treatment. Although different morphological patterns can be
      seen on light microscopy, granulomatous reaction and giant cells are a very rare
      occurrence. We report the case of a young female with ovarian yolk-sac tumor in
      which a widespread granulomatous reaction was seen, causing a diagnostic dilemma.

PMID- 24585356
TI  - Interobserver agreement among histological patterns and diagnosis in lung
      adenocarcinomas.
AB  - OBJECTIVE: The aim of this study was to investigate the interobserver agreement
      in determination of the dominant histological pattern and the final diagnosis in
      lung adenocarcinomas. MATERIAL AND METHOD: A total of 12 patients with a
      diagnosis of primary lung adenocarcinoma were included in the study. Twelve
      pathologists from eight study centers were asked first to determine the dominant
      histological pattern in these cases and then to decide whether the final
      diagnosis was in situ, minimally invasive or invasive adenocarcinoma. RESULTS:
      The kappa value for the agreement in determining the dominant pattern among the
      pathologists was 0.36 (p < 0.001), with the values for the lepidic, acinar,
      papillary, solid, micropapillary patterns and mucinous character of
      adenocarcinoma being 0.34, 0.28, 0.30, 0.80, 0.16 and 0.38 respectively (p <
      0.001, p < 0.001, p < 0.001, p < 0.001, p < 0.001, p < 0.001). None of the cases
      was diagnosed as in situ adenocarcinoma. On the other hand, the kappa value for
      the agreement in differentiating minimally invasive from invasive adenocarcinoma
      among reviewers was 0.17 (p < 0.001). CONCLUSION: The agreement among
      pathologists in determining the subtype of lung adenocarcinomas that depends on
      the identification of the dominant pattern was at intermediate level. In
      addition, the agreement in deciding whether the case is minimally invasive or
      invasive, was at low level. The criteria defining the histological patterns
      should be clarified and described in more detail. Educational activities and
      larger multicenter studies might be helpful in improving the agreement and
      standardization.

PMID- 24585357
TI  - Chemometric methods for the quantification of crystalline tacrolimus in solid
      dispersion by powder X-ray diffractrometry.
AB  - The objective of this study was to develop powder X-ray diffraction (XRPD)
      chemometric model for quantifying crystalline tacrolimus from solid dispersion
      (SD). Three SDs (amorphous tacrolimus component) with varying drug to excipient
      ratios (24.4%, 6.7%, and 4.3% drug) were prepared. Placebo SDs were mixed with
      crystalline tacrolimus to make their composition equivalent to three SD
      (crystalline tacrolimus component). These two components were mixed to cover 0%
      100% of crystalline drug. Uniformity of the sample mixtures was confirmed by near
      infrared chemical imaging. XRPD showed three distinct peaks of crystalline drug
      at 8.5 degrees , 10.3 degrees , and 11.2 degrees  (2theta), which were
      nonoverlapping with the excipients. Principal component regressions (PCR) and
      partial least square (PLS) regression used in model development showed high R(2)
      (>0.99) for all the mixtures. Overall, the model showed low root mean square of
      standard error, standard error, and bias, which was smaller in PLS than PCR-based
      model. Furthermore, the model performance was evaluated on the formulations with
      known percentage of crystalline drug. Model-calculated crystalline drug
      percentage values were close to actual value. Therefore, these studies strongly
      suggest the application of chemometric-XRPD models as a quality control tool to
      quantitatively predict the crystalline drug in the formulation.

PMID- 24585358
TI  - The Mozzafari Hospital of Shiraz, Persia.
AB  - INTRODUCTION: This article discusses three significant hospitals that were
      constructed in medieval Persia, specifically in the city of Shiraz, which is
      located in central present-day Iran. The first of these three hospitals is the
      Azodi Hospital, which was constructed during the Buyid dynasty. The second
      hospital was constructed during the Salghurid dynasty and is referred to as the
      Mozzafari Hospital by a primary source written by Qutb al-Din Shirazi, a
      physician who worked there. The third hospital is also referred to as the
      Mozzafari Hospital and was constructed during the Mozzafarid dynasty. Recent
      efforts have yielded archaeological evidence that marks the location in present
      day Shiraz of this third hospital or an area south of its location. The evidence
      consists of the gravesite for Seyed Sharaf al-Din Jorjani, a prominent theologian
      who was employed by Shah Shoja of the Mozzafarid dynasty in the fourteenth
      century CE. at the compound containing the third hospital. CONCLUSION: The
      gravesite for Sharaf al-Din Jorjani in present-day Shiraz marks the site of the
      remains of the Mozzafari Hospital built during the reign of Shah Shoja of the
      Mozzafarid dynasty or an area south of Shah Shoja's Mozzafari Hospital.

PMID- 24585359
TI  - Experimental tools to monitor the dynamics of endothelial barrier function: a
      survey of in vitro approaches.
AB  - Endothelial cells line the inner surface of all blood vessels and constitute a
      selective barrier between blood and tissue. Permeation of solutes across the
      endothelial cell monolayer occurs either paracellularly through specialized
      endothelial cell-cell junctions or transcellularly via special transport
      mechanisms including transcytosis, via the formation of transcellular channels,
      or by cell membrane transport proteins. Several in vitro assays have been
      developed in the past few decades to analyze the molecular mechanisms of
      transendothelial permeability. Measurement of the electrical resistance of the
      cell monolayer has proven to be particularly suitable for analyzing paracellular
      barrier function with high-time resolution over long time periods. We review the
      various permeability assays and focus on the electrical impedance analysis of
      endothelial cell monolayers. We also address current progress in the development
      of techniques used to investigate endothelial permeability with high-lateral
      resolution and under mechanical loads. 

PMID- 24585360
TI  - Strategies to overcome the barrier: use of nanoparticles as carriers and
      modulators of barrier properties.
AB  - The blood-brain barrier (BBB) protects the brain from toxic substances within the
      bloodstream and keeps the brain's homeostasis stable. On the other hand, it also
      represents the main obstacle in the treatment of many CNS diseases. Among
      different techniques, nanoparticles have emerged as promising tools to enhance
      brain drug delivery of therapeutic molecules. For successful drug delivery,
      nanoparticles may either modulate BBB integrity or exploit transport systems
      present on the endothelium. In this review, we present two different
      nanoparticles to enhance brain drug delivery. Poly(butyl cyanoacrylate)
      nanoparticles were shown to induce a reversible disruption of the BBB in vitro
      which may be exploited by simultaneous injection of the drug in question. By
      coating the poly(butyl cyanoacrylate) nanoparticles with, e.g., ApoE, it is also
      possible to circumvent the BBB via the LDL-receptor. Another example of the use
      of receptor-mediated endocytosis to enhance brain uptake of nanoparticles are
      poly(ethylene glycol)-coated Fe3O4 nanoparticles which are covalently attached to
      lactoferrin. These nanoparticles have been shown to facilitate the transport via
      the lactoferrin receptor, and so could then be used for magnetic resonance
      imaging. 

PMID- 24585361
TI  - What are the surveillance recommendations following resection of sinonasal
      inverted papilloma?

PMID- 24585362
TI  - A cam deformity is gradually acquired during skeletal maturation in adolescent
      and young male soccer players: a prospective study with minimum 2-year follow-up.
AB  - BACKGROUND: A cam deformity is a major risk factor for hip osteoarthritis, and
      its formation is thought to be influenced by high-impact sporting activities
      during growth. PURPOSE: To (1) prospectively study whether a cam deformity can
      evolve over time in adolescents and whether its formation only occurs during
      skeletal maturation and (2) examine whether clinical or radiographic features can
      predict the formation of a cam deformity. STUDY DESIGN: Cohort study (prognosis);
      Level of evidence, 2. METHODS: Preprofessional soccer players (N = 63; mean age,
      14.43 years; range, 12-19 years) participated both at baseline and follow-up
      (mean follow-up, 2.4 +/- 0.06 years). At both time points, standardized
      anteroposterior and frog-leg lateral radiographs were obtained. For each hip, the
      alpha angle was measured, and the anterosuperior head-neck junction was
      classified by a 3-point visual system as normal, flattened, or having a
      prominence. Differences between baseline and follow-up values for the alpha angle
      and the prevalence of each visual hip classification were calculated.
      Additionally, the amount of internal hip rotation, growth plate extension into
      the neck, and neck shaft angle were determined. RESULTS: Overall, there was a
      significant increase in the prevalence of a cam deformity during follow-up. In
      boys aged 12 and 13 years at baseline, the prevalence of a flattened head-neck
      junction increased significantly during follow-up (13.6% to 50.0%; P = .002). In
      all hips with an open growth plate at baseline, the prevalence of a prominence
      increased from 2.1% to 17.7% (P = .002). After closure of the proximal femoral
      growth plate, there was no significant increase in the prevalence or increase in
      severity of a cam deformity. The alpha angle increased significantly from 59.4
      degrees  at baseline to 61.3 degrees  at follow-up (P = .018). The amount of
      growth plate extension was significantly associated with the alpha angle and hip
      classification (P = .001). A small neck shaft angle and limited internal rotation
      were associated with cam deformities and could also significantly predict the
      formation of cam deformities (alpha angle >60 degrees ) at follow-up. CONCLUSION:
      In youth soccer players, cam deformities gradually develop during skeletal
      maturation and are probably stable from the time of growth plate closure. The
      formation of a cam deformity might be prevented by adjusting athletic activities
      during a small period of skeletal growth, which will have a major effect on the
      prevalence of hip osteoarthritis.

PMID- 24585363
TI  - Clinical outcomes do not support arthroscopic posterior capsular release in
      addition to anterior release for shoulder stiffness: a randomized controlled
      study.
AB  - BACKGROUND: Arthroscopic capsular release is an effective treatment for shoulder
      stiffness, yet its extent is controversial. PURPOSE: To compare the clinical
      outcomes of arthroscopic capsular release in patients with and without posterior
      extended capsular release for shoulder stiffness. STUDY DESIGN: Randomized
      controlled trial; Level of evidence, 1. METHODS: Between January 2008 and March
      2011, 75 patients who underwent arthroscopic capsular release for shoulder
      stiffness were enrolled and randomized into 2 groups. In group I (n = 37),
      capsular release was performed, including release of the rotator interval and
      anterior and inferior capsule. In group II (n = 38), capsular release was
      extended to the posterior capsule. The American Shoulder and Elbow Surgeons
      score, Simple Shoulder Test, visual analog scale for pain, and range of motion
      (ROM) were used for the evaluation before surgery and at 3, 6, and 12 months
      after surgery and at the last follow-up. RESULTS: Preoperative demographic data
      of age, sex, symptom duration, and clinical outcomes showed no significant
      differences (P > .05). The average follow-up was 18.4 months. Both groups showed
      significantly increased ROM at the last follow-up compared with preoperative ROM
      (P < .05). At the last follow-up, no statistical differences were found (P > .05)
      between groups I and II in American Shoulder and Elbow Surgeons score (91.3 vs.
      79.5), Simple Shoulder Test (83.3 vs. 83.3), and visual analog scale (1.5 vs.
      2.2). There were also no statistical differences between the 2 groups at the last
      follow-up (P > .05) in ROM: forward flexion, 145.2 degrees  vs. 143.3 degrees ;
      external rotation with 90 degrees  of abduction, 88.1 degrees  vs. 86.2 degrees ;
      external rotation at side, 88.9 degrees  vs. 82.9 degrees ; and internal
      rotation, 9.1 degrees  vs. 8.3 degrees . CONCLUSION: Posterior extended capsular
      release might not be necessary in arthroscopic surgery for shoulder stiffness.

PMID- 24585364
TI  - [Thrombosis of the external jugular vein. Case report of a rare cause for pain in
      the lateral neck].
AB  - Dental practitioners are sometimes confronted with patients complaining about
      pain in the neck area. Especially if an induration in the region of the big
      vessels is present, one must keep in mind the differential diagnosis of a
      spontaneous thrombosis of the external jugular vein. This diagnosis needs
      consequent treatment but also consequent search for an underlying pathology. This
      case report presents such a situation in an exemplary way. Despite risk factors,
      the reason for thrombosis stays in the dark. However, all possible causes were
      cleared and are shown to the reader. Especially malignancies are responsible for
      thrombosis of the jugular vein in many cases. 

PMID- 24585365
TI  - Plasmapheresis combined with rituximab for refractory idiopathic membranous
      nephropathy.

PMID- 24585366
TI  - Correlation of morphological pattern of optical coherence tomography in diabetic
      macular edema with systemic risk factors in middle aged males.
AB  - To study correlation of different optical coherence tomography (OCT) patterns of
      diabetic macular edema (DME) with systemic risk factors. Institutional cross
      sectional double-masked non-interventional study with 330 eyes of middle-aged
      male type 2 diabetes patients with DME. Various systemic parameters were
      measured. Diffuse retinal thickening (DRT), cystoid and serous patterns of DME
      were identified on OCT. Comparison between DRT versus non-DRT and serous versus
      non-serous eyes was done in respect to systemic parameters. Correlation of serous
      and DRT pattern was tested with systemic parameters above and below specified
      values. Mean age was 54.4 +/- 7.1 years. Mean duration of diabetes was 8.7 +/-
      4.2 years. Mean serum globulin level was significantly higher (p = 0.018) in
      serous compared to non-serous group. Prevalence of serous DME was significantly
      high in those with serum globulin level >3.5 gm/dl (prevalence ratio = 3.01, p =
      0.040). Significant correlation of central macular thickness was observed with
      duration of diabetes (p = 0.002, r = 0.440).Visual acuity (logMAR) was correlated
      significantly with HbA1C (p = 0.031, r = 0.305). Increased serum globulin, a
      positive phase reactant of inflammation, was found significant independent risk
      factor for development of serous DME. This study did not identify any modifiable
      systemic factor for any of the OCT patterns in DME.

PMID- 24585367
TI  - Mild to moderate Alzheimer dementia with insufficient neuropathological changes.
AB  - Recently, ~16% of participants in an anti-Abeta passive immunotherapy trial for
      mild-to-moderate Alzheimer disease (AD) had a negative baseline amyloid positron
      emission tomography (PET) scan. Whether they have AD or are AD clinical
      phenocopies remains unknown. We examined the 2005-2013 National Alzheimer's
      Coordinating Center autopsy database and found that ~14% of autopsied subjects
      clinically diagnosed with mild-to-moderate probable AD have no or sparse neuritic
      plaques, which would expectedly yield a negative amyloid PET scan. More than half
      of these "Abeta-negative" subjects have low neurofibrillary tangle Braak stages.
      These findings support the implementation of a positive amyloid biomarker as an
      inclusion criterion in future anti-Abeta drug trials.

PMID- 24585368
TI  - Ab-initio study of structural, electronic, and transport properties of zigzag GaP
      nanotubes.
AB  - Stability and electronic properties of zigzag (3 <= n <= 16) gallium phosphide
      nanotubes (GaP NTs) have been analyzed by employing a systematic ab-intio
      approach based on density functional theory using generalized gradient
      approximation with revised Perdew Burke Ernzerhoff type parameterization.
      Diameter dependence of bond length, buckling, binding energy, and band gap has
      been investigated and the analysis shows that the bond length and buckling
      decreases with increasing diameter of the tube, highest binding energy of (16, 0)
      confirms this as the most stable amongst all the NTs taken into consideration.
      The present GaP NTs shows direct band gap and it increases with diameter of the
      tubes. Using a two probe model for (4, 0) NT the I-V relationship shows an
      exponential increase in current on applying bias voltage beyond 1.73 volt. 

PMID- 24585369
TI  - McConnell's sign: an early and specific indicator of acute pulmonary embolism.

PMID- 24585371
TI  - Can lingual tonsillectomy improve persistent pediatric obstructive sleep apnea?

PMID- 24585372
TI  - 'Candidatus Phytoplasma palmicola', associated with a lethal yellowing-type
      disease of coconut (Cocos nucifera L.) in Mozambique.
AB  - In this study, the taxonomic position and group classification of the phytoplasma
      associated with a lethal yellowing-type disease (LYD) of coconut (Cocos nucifera
      L.) in Mozambique were addressed. Pairwise similarity values based on alignment
      of nearly full-length 16S rRNA gene sequences (1530 bp) revealed that the
      Mozambique coconut phytoplasma (LYDM) shared 100% identity with a comparable
      sequence derived from a phytoplasma strain (LDN) responsible for Awka wilt
      disease of coconut in Nigeria, and shared 99.0-99.6% identity with 16S rRNA gene
      sequences from strains associated with Cape St Paul wilt (CSPW) disease of
      coconut in Ghana and Cote d'Ivoire. Similarity scores further determined that the
      16S rRNA gene of the LYDM phytoplasma shared <97.5% sequence identity with all
      previously described members of 'Candidatus Phytoplasma'. The presence of unique
      regions in the 16S rRNA gene sequence distinguished the LYDM phytoplasma from all
      currently described members of 'Candidatus Phytoplasma', justifying its
      recognition as the reference strain of a novel taxon, 'Candidatus Phytoplasma
      palmicola'. Virtual RFLP profiles of the F2n/R2 portion (1251 bp) of the 16S rRNA
      gene and pattern similarity coefficients delineated coconut LYDM phytoplasma
      strains from Mozambique as novel members of established group 16SrXXII, subgroup
      A (16SrXXII-A). Similarity coefficients of 0.97 were obtained for comparisons
      between subgroup 16SrXXII-A strains and CSPW phytoplasmas from Ghana and Cote
      d'Ivoire. On this basis, the CSPW phytoplasma strains were designated members of
      a novel subgroup, 16SrXXII-B.

PMID- 24585370
TI  - Modified silicone elastomer vaginal gels for sustained release of antiretroviral
      HIV microbicides.
AB  - We previously reported nonaqueous silicone elastomer gels (SEGs) for sustained
      vaginal administration of the CCR5-targeted entry inhibitor maraviroc (MVC).
      Here, we describe chemically modified SEGs (h-SEGs) in which the hydrophobic
      cyclomethicone component was partially replaced with relatively hydrophilic
      silanol-terminated polydimethylsiloxanes (st-PDMS). MVC and emtricitabine (a
      nucleoside reverse transcriptase inhibitor), both currently under evaluation as
      topical microbicides to counter sexual transmission of human immunodeficiency
      virus type 1 (HIV-1), were used as model antiretroviral (ARV) drugs. Gel
      viscosity and in vitro ARV release were significantly influenced by st-PDMS
      molecular weight and concentration in the h-SEGs. Unexpectedly, gels prepared
      with lower molecular weight grades of st-PDMS showed higher viscosities. h-SEGs
      provided enhanced release over 24 h compared with aqueous hydroxyethylcellulose
      (HEC) gels, did not modify the pH of simulated vaginal fluid (SVF), and were
      shown to less cytotoxic than standard HEC vaginal gel. ARV solubility increased
      as st-PDMS molecular weight decreased (i.e., as percentage hydroxyl content
      increased), helping to explain the in vitro release trends. Dye ingression and
      SVF dilution studies confirmed the increased hydrophilicity of the h-SEGs. h-SEGs
      have potential for use in vaginal drug delivery, particularly for ARV-based HIV-1
      microbicides.

PMID- 24585373
TI  - Xenophilus arseniciresistens sp. nov., an arsenite-resistant bacterium isolated
      from soil.
AB  - A Gram-reaction-negative, aerobic, motile, rod-shaped, arsenite [As(III)]
      resistant bacterium, designated strain YW8(T), was isolated from agricultural
      soil. 16S rRNA gene sequence analysis showed over 97% sequence similarity to
      strains of the environmental species Xenophilus azovorans, Xenophilus aerolatus,
      Simplicispira metamorpha, Variovorax soli, and Xylophilus ampelinus. However, the
      phylogenetic tree indicated that strain YW8(T) formed a separate clade from
      Xenophilus azovorans. DNA-DNA hybridization experiments showed that the DNA-DNA
      relatedness values between strain YW8(T) and its closest phylogenetic neighbours
      were below 24.2-35.5%, which clearly separated the strain from these closely
      related species. The major cellular fatty acids of strain YW8(T) were C(16 : 0),
      C(17 : 0) cyclo, C(18 : 1)omega7c, and summed feature 3(C(16 : 1)omega6c and/or
      C(16 : 1)omega7c). The genomic DNA G+C content was 69.3 mol%, and the major
      respiratory quinone was ubiquinone-8. The predominant polar lipids were
      diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, three
      unknown phospholipids, an unknown polar lipid and phosphatidylserine. The major
      polyamines were 2-hydroxyputrescine and putrescine. On the basis of
      morphological, physiological and biochemical characteristics, phylogenetic
      position, DNA-DNA hybridization and chemotaxonomic data, strain YW8(T) is
      considered to represent a novel species of the genus Xenophilus, for which the
      name Xenophilus arseniciresistens sp. nov. is proposed; the type strain is YW8(T)
      ( = CCTCC AB2012103(T) = KACC 16853(T)).

PMID- 24585374
TI  - Eoetvoesia caeni gen. nov., sp. nov., isolated from an activated sludge system
      treating coke plant effluent.
AB  - A novel bacterium, PB3-7B(T), was isolated on phenol-supplemented inorganic
      growth medium from a laboratory-scale wastewater purification system that treated
      coke plant effluent. 16S rRNA gene sequence analysis revealed that strain PB3
      7B(T) belonged to the family Alcaligenaceae and showed the highest pairwise
      sequence similarity to Parapusillimonas granuli Ch07(T) (97.5%), Candidimonas
      bauzanensis BZ59(T) (97.3%) and Pusillimonas noertemannii BN9(T) (97.2%). Strain
      PB3-7B(T) was rod-shaped, motile and oxidase- and catalase-positive. The
      predominant fatty acids were C(16 : 0), C(17 : 0) cyclo, C(19 : 0) cyclo omega8c
      and C(14 : 0) 3-OH, and the major respiratory quinone was Q-8. The G+C content of
      the genomic DNA of strain PB3-7B(T) was 59.7 mol%. The novel bacterium can be
      distinguished from closely related type strains based on its urease activity and
      the capacity for assimilation of glycerol and amygdalin. On the basis of the
      phenotypic, chemotaxonomic and molecular data, strain PB3-7B(T) is considered to
      represent a new genus and species, for which the name Eoetvoesia caeni gen. nov.,
      sp. nov. is proposed. The type strain of Eoetvoesia caeni is PB3-7B(T) ( = DSM
      25520(T) = NCAIM B 02512(T)).

PMID- 24585375
TI  - Description of Helicobacter valdiviensis sp. nov., an Epsilonproteobacteria
      isolated from wild bird faecal samples.
AB  - Two Gram-stain-negative, gently curved rod-shaped isolates (WBE14(T) and WBE19),
      recovered from wild bird faecal samples in the city of Valdivia (Southern Chile)
      were subjected to a polyphasic taxonomic study. Results of a genus-specific PCR
      indicated that these isolates belonged to the genus Helicobacter. This was
      further confirmed by a phylogenetic analyses based on the 16S rRNA, 60 kDa heat
      shock protein (cpn60) and gyrase subunit B (gyrB) genes, where both strains
      formed a novel phylogenetic line within this genus. The 16S rRNA gene sequence
      similarity of strain WBE14(T) to the type strains of all other species of the
      genus Helicobacter examined ranged from 89.4 to 97.0%; Helicobacter brantae and
      Helicobacter pametensis were the most closely related species. However, on the
      basis of the protein-coding genes Helicobacter pullorum and Helicobacter
      canadensis are the most closely related species. These data, together with their
      different morphological and biochemical characteristics, revealed that these
      strains represent a novel species, for which the name Helicobacter valdiviensis
      sp. nov. is proposed, with the type strain WBE14(T) ( = CECT 8410(T) = LMG
      27920(T)).

PMID- 24585376
TI  - Bradyrhizobium ganzhouense sp. nov., an effective symbiotic bacterium isolated
      from Acacia melanoxylon R. Br. nodules.
AB  - Three slow-growing rhizobial strains, designated RITF806(T), RITF807 and RITF211,
      isolated from root nodules of Acacia melanoxylon grown in Ganzhou city, Jiangxi
      Province, China, had been previously defined, based on amplified 16S rRNA gene
      restriction analysis, as a novel group within the genus Bradyrhizobium. To
      clarify their taxonomic position, these strains were further analysed and
      compared with reference strains of related bacteria using a polyphasic approach.
      According to 16S rRNA gene sequence analysis, the isolates formed a group that
      was closely related to 'Bradyrhizobium rifense' CTAW71, with a similarity value
      of 99.9%. In phylogenetic analyses of the housekeeping and symbiotic gene
      sequences, the three strains formed a distinct lineage within the genus
      Bradyrhizobium, which was consistent with the results of DNA-DNA hybridization.
      In analyses of cellular fatty acids and phenotypic features, some differences
      were found between the novel group and related species of the genus
      Bradyrhizobium, indicating that these three strains constituted a novel group
      distinct from any recognized species of the genus Bradyrhizobium. Based on the
      data obtained in this study, we conclude that our strains represent a novel
      species of the genus Bradyrhizobium, for which the name Bradyrhizobium
      ganzhouense sp. nov. is proposed, with RITF806(T) ( = CCBAU 101088(T) = JCM
      19881(T)) as the type strain. The DNA G+C content of strain RITF806(T) is 64.6
      mol% (T(m)).

PMID- 24585377
TI  - Marek's disease virus may interfere with T cell immunity by TLR3 signals.
AB  - Marek's disease virus (MDV) is a highly oncogenic alpha-herpesvirus that causes T
      cell immune suppression and malignant lymphomas in chickens. Toll-like receptor
      (TLR) plays a dominant role in antiviral T cell immunity. However, it is unclear
      whether MDV induced T cell immunity is associated with TLR-mediated immunity. In
      this study, the expression of 28 host genes that are involved in TLR-mediated
      immunity and MHC-medicated T cell immunity was evaluated in chicken thymus at 7,
      14, 21 and 28 days post-infection (dpi). Our results demonstrated that 24 host
      immune-related genes were upregulated during MDV infection at 7 dpi; however, the
      expression of most of these genes decreased at 21 and 28 dpi. Notably, a positive
      correlation was found between the down-regulation of CD4, CD8 and TLR3 signals
      but not the MyD88-dependent TLR pathway. The present study expanded our knowledge
      of host immune responses against MDV infection and our results might provide a
      clue that MDV may interfere with T cell immune response through TLR3 signals. 

PMID- 24585378
TI  - A simple semi-preparative reversed-phase HPLC/PDA method for separation and
      quantification of glycyrrhizin in nine samples of Glycyrrhiza glabra root
      collected from different geographical origins.
AB  - INTRODUCTION: Glycyrrhiza glabra L. (Fabaceae), commonly known as 'liquorice', is
      one of the most popular ingredients in several traditional herbal medicinal
      preparations, and glycyrrhizin is the major glycoside present in this plant. The
      content of glycyrrhizin may vary among G. glabra samples collected from various
      geographical origins, which may affect the therapeutic efficacy. Thus,
      quantification of glycyrrhizin in G. glabra samples is important. OBJECTIVE: To
      develop and validate a simple semi-preparative reversed-phase HPLC with
      photodiode array (PDA) method for separation and quantification of glycyrrhizin
      in nine samples of G. glabra root collected from various geographical origins.
      METHODS: Dried and ground root of G. glabra was Soxhlet-extracted sequentially
      with n-hexane and methanol (MeOH). The separation and quantification of
      glycyrrhizin was achieved on a C18 reversed-phase semi-preparative column using a
      gradient mobile phase, 30-100% solvent B in solvent A in 30 min (solvent A: 0.1%
      v/v trifluoroacetic acid (TFA) in water and solvent B: 0.1% v/v of TFA in MeOH),
      at a flow rate of 3.00 mL/min and UV detection at 254 nm. RESULTS: A simple semi
      preparative reversed-phase HPLC/PDA method allowing clear separation and
      quantification of glycyrrhizin content in nine samples has been validated in
      terms of linearity, selectivity, limits of detection, precision, accuracy and
      detection. Concentration levels of glycyrrhizin were between 0.177 and 0.688% w/w
      of dry materials. CONCLUSION: This method is precise, less time consuming and
      more cost effective, and can be used for the quality control of any G. glabra
      sample with regard to its glycyrrhizin contents.

PMID- 24585379
TI  - Exercise during growth and young adulthood is independently associated with
      cortical bone size and strength in old Swedish men.
AB  - Previous studies have reported an association between exercise during youth and
      increased areal bone mineral density at old age. The primary aim of this study
      was to investigate if exercise during growth was independently associated with
      greater cortical bone size and whole bone strength in weight-bearing bone in old
      men. The tibia and radius were measured using both peripheral quantitative
      computed tomography (pQCT) (XCT-2000; Stratec) at the diaphysis and high
      resolution pQCT (HR-pQCT) (XtremeCT; Scanco) at the metaphysis to obtain cortical
      bone geometry and finite element-derived bone strength in distal tibia and
      radius, in 597 men, 79.9 +/- 3.4 (mean +/- SD) years old. A self-administered
      questionnaire was used to collect information about previous and current physical
      activity. In order to determine whether level of exercise during growth and young
      adulthood or level of current physical activity were independently associated
      with bone parameters in both tibia and radius, analysis of covariance (ANCOVA)
      analyses were used. Adjusting for covariates and current physical activity, we
      found that men in the group with the highest level of exercise early in life
      (regular exercise at a competitive level) had higher tibial cortical cross
      sectional area (CSA; 6.3%, p < 0.001) and periosteal circumference (PC; 1.6%, p =
      0.011) at the diaphysis, and higher estimated bone strength (failure load: 7.5%,
      p < 0.001; and stiffness: 7.8%, p < 0.001) at the metaphysis than men in the
      subgroup with the lowest level of exercise during growth and young adulthood.
      Subjects in the group with the highest level of current physical activity had
      smaller tibial endosteal circumference (EC; 3.6%, p = 0.012) at the diaphysis
      than subjects with a lower current physical activity, when adjusting for
      covariates and level of exercise during growth and young adulthood. These
      findings indicate that exercise during growth can increase the cortical bone size
      via periosteal expansion, whereas exercise at old age may decrease endosteal bone
      loss in weight-bearing bone in old men.

PMID- 24585380
TI  - Purification and characterization of the glucoside 3-dehydrogenase produced by a
      newly isolated Sphingobacterium faecium ZJF-D6 CCTCC M 2013251.
AB  - A soluble glucoside 3-dehydrogenase (G3DH) was purified from a newly isolated
      Sphingobacterium faecium ZJF-D6 CCTCC M 2013251. The enzyme was purified to 35.71
      fold with a yield of 41.91 % and was estimated by sodium dodecyl sulphate
      polyacrylamide gel electrophoresis with a molecular mass of 62 kDa. The sequences
      of two peptides of the enzyme were all contained in a GMC family oxidoreductase
      (EFK55866) by mass spectrometry analysis. The optimal pH of the enzyme was around
      6.2. The enzyme was stable within a pH range of 5.0-6.6 and was sensitive to
      heat. G3DH from S. faecium exhibited extremely broad substrate specificity and
      well regioselectivity to validoxylamine A. The enzyme was completely inhibited by
      Hg2Cl2 and partly inhibited by Cu(2+), Fe(2+), Ca(2+), and Cd(2+). The apparent K
      m values for D-glucose, sucrose, and validoxylamine were calculated to be 1.1,
      1.7, and 2.1 mM, respectively. With this purified enzyme, 3-keto sucrose was
      prepared at pH 5.0, 30  degrees C for 10 h with a yield of 28.7 %.

PMID- 24585381
TI  - Self-oligomerization of ASC PYD domain prevents the assembly of inflammasome in
      vitro.
AB  - NALP3 inflammasome, which is an inflammatory caspase-activating complex, is
      composed of three proteins: NALP3 (an NOD-like receptor), an apoptosis-associated
      speck-like protein containing a caspase recruitment domain (ASC), and caspase-1.
      NALP3 senses danger signals, while ASC is an adaptor molecule containing two
      protein interaction modules: pyrin domain (PYD) and caspase recruitment domain
      (CARD). Caspase-1 is a cysteine protease that uses cysteine as a nucleophile and
      has a CARD domain for protein interaction. During inflammasome formation, the ASC
      adaptor acts as a bridge between caspase and NOD-like receptor (NLR) by offering
      the CARD for CARD-CARD interactions and PYD for PYD-PYD interactions. In the
      current study, we successfully purified and characterized NALP3 PYD and ASC PYD.
      The results showed that ASC PYD easily self-oligomerized under physiological
      conditions, and this self-oligomerization of the ASC PYD prevented complex
      formation with NALP3 PYD in vitro.

PMID- 24585382
TI  - Purification and biochemical characterization of a novel alkaline protease
      produced by Penicillium nalgiovense.
AB  - Penicillium nalgiovense PNA9 produces an extracellular protease during
      fermentation with characteristics of growth-associated product. Enzyme
      purification involved ammonium sulfate precipitation, dialysis, and
      ultrafiltration, resulting in 12.1-fold increase of specific activity (19.5
      U/mg). The protein was isolated through a series of BN-PAGE and native PAGE runs.
      ESI-MS analysis confirmed the molecular mass of 45.2 kDa. N-Terminal sequencing
      (MGFLKLLKGSLATLAVVNAGKLLTANDGDE) revealed 93 % similarity to a Penicillium
      chrysogenum protease, identified as major allergen. The protease exhibits simple
      Michaelis-Menten kinetics and K m (1.152 mg/ml), V max (0.827 mg/ml/min), and k
      cat (3.2 * 10(2)) (1/s) values against azocasein show that it possesses high
      substrate affinity and catalytic efficiency. The protease is active within 10-45 
      degrees C, pH 4.0-10.0, and 0-3 M NaCl, while maximum activity was observed at 35
      degrees C, pH 8.0, and 0.25 M NaCl. It is active against the muscle proteins
      actin and myosin and inactive against myoglobin. It is highly stable in the
      presence of non-ionic surfactants, hydrogen peroxide, BTNB, and EDTA. Activity
      was inhibited by SDS, Mn(2+) and Zn(2+), and by the serine protease inhibitor
      PMSF, indicating the serine protease nature of the enzyme. These properties make
      the novel protease a suitable candidate enzyme in meat ripening and other
      biotechnological applications.

PMID- 24585383
TI  - Mutations in mammalian target of rapamycin regulator DEPDC5 cause focal epilepsy
      with brain malformations.
AB  - We recently identified DEPDC5 as the gene for familial focal epilepsy with
      variable foci and found mutations in >10% of small families with nonlesional
      focal epilepsy. Here we show that DEPDC5 mutations are associated with both
      lesional and nonlesional epilepsies, even within the same family. DEPDC5
      associated malformations include bottom-of-the-sulcus dysplasia (3 members from 2
      families), and focal band heterotopia (1 individual). DEPDC5 negatively regulates
      the mammalian target of rapamycin (mTOR) pathway, which plays a key role in cell
      growth. The clinicoradiological phenotypes associated with DEPDC5 mutations share
      features with the archetypal mTORopathy, tuberous sclerosis, raising the
      possibility of therapies targeted to this pathway.

PMID- 24585384
TI  - Knowledge of halitosis among dentists and dental hygienists.
AB  - Bad breath is a widespread condition that has been increasingly discussed among
      professionals and in the mass media in the last few years. In nine of ten cases,
      halitosis originates intraorally; hence it has become an important topic of study
      in the education and training of dentists and dental hygienists. However, the de
      facto knowledge of professionals has never been examined until today. 750
      dentists and dental hygienists from Switzerland, Germany, and France were
      personally interviewed. Their knowledge of halitosis was assessed using a
      specifically designed questionnaire. In general, considerable differences were
      ascertained between the German-speaking countries and France, dentists and dental
      hygienists, and women and men. 27.5% of the French participants believed that the
      underlying cause of halitosis has a non-oral nature, whereas only 8% of the Swiss
      and German participants believed so (p ? 0.001). In contrast to dental
      hygienists, dentists more often considered gastrointestinal factors as a cause of
      halitosis (p ? 0.001). Dental hygienists from Switzerland and Germany more
      frequently reported the use of tongue scrapers as a therapeutic method (97% and
      97.3%) than did dentists of the same countries (87.3% and 89.3%). Among the
      French participants, only 52% mentioned the use of tongue scrapers to treat
      halitosis. 2.7% of French dental professionals had participated in a continuing
      education course about halitosis, which is much lower than the rate of attendance
      in Switzerland and Germany (46%). Additionally, interdisciplinary discrepancies
      were observed, as 65.3% of the dental hygienists frequented advanced training
      courses, which was twice as much as dentists. Therefore, there are clear
      differences between dentists in France and their colleagues from the German
      speaking countries, but also between dental hygienists and dentists. Dental
      hygienists from Switzerland and Germany appear to be far ahead in terms of
      halitosis knowledge. 

PMID- 24585385
TI  - Mentoring by design: integrating medical professional competencies into
      bioengineering and medical physics graduate training.
AB  - Many students in bioengineering and medical physics doctoral programs plan
      careers in translational research. However, while such students generally have
      strong quantitative abilities, they often lack experience with the culture,
      communication norms, and practice of bedside medicine. This may limit students'
      ability to function as members of multidisciplinary translational research teams.
      To improve students' preparation for careers in cancer translational research, we
      developed and implemented a mentoring program that is integrated with students'
      doctoral studies and aims to promote competencies in communication, biomedical
      ethics, teamwork, altruism, multiculturalism, and accountability. Throughout the
      program, patient-centered approaches and professional competencies are presented
      as foundational to optimal clinical care and integral to translational research.
      Mentoring is conducted by senior biomedical faculty and administrators and
      includes didactic teaching, online learning, laboratory mini-courses, clinical
      practicums, and multidisciplinary patient planning conferences (year 1); student
      development and facilitation of problem-based patient cases (year 2); and
      individualized mentoring based on research problems and progress toward degree
      completion (years 3-5). Each phase includes formative and summative evaluations.
      Nineteen students entered the program from 2009 through 2011. On periodic
      anonymous surveys, the most recent in September 2013, students indicated that the
      program substantially improved their knowledge of cancer biology, cancer
      medicine, and academic medicine; that the mentors were knowledgeable, good
      teachers, and dedicated to students; and that the program motivated them to
      become well-rounded scientists and scholars. We believe this program can be
      modified and disseminated to other graduate research and professional health care
      programs. 

PMID- 24585387
TI  - Re: comparison between prenatal ultrasound and postmortem findings in fetuses and
      infants with developmental anomalies.

PMID- 24585386
TI  - Selenium:mercury molar ratios in bullfrog and leopard frog tadpoles from the
      northeastern United States.
AB  - Vertebrates experience adverse effects from methylmercury, largely obtained
      through their food. Selenium has the potential to reduce the toxic effects of
      methylmercury (and vice versa). In this paper, we examine the selenium:mercury
      molar ratios in tadpoles (Lithobates sphenocephalus, Lithobates catesbeianus
      (formerly Rana), and a newly documented leopard frog species currently referred
      to as R. sp. nov.) and fully formed leopard frog metamorphs. There were no
      significant differences in metal levels between the two leopard frog species, and
      data were therefore combined. Selenium:mercury molar ratios varied from 19 to 38
      for bullfrog tadpoles, from 16 to 330 for leopard frog tadpoles, and from 7 to 17
      for leopard frog metamorphs. Leopard frog tadpoles with less than 45 days
      exposure to field conditions had significantly higher molar ratios than other
      tadpoles and leopard frog metamorphs. There were significant locational
      differences for the molar ratios of bullfrogs, and leopard frog tadpoles with
      more than 45 days of field exposure. At the sites where we were able to sample
      both leopard frog tadpoles and leopard frog metamorphs, there were significant
      differences between the two distinct life stages. Most of the variation in the
      ratio was accounted for by selenium levels, field sites, and exposure period. 

PMID- 24585388
TI  - The role of albumin and PPAR-alpha in differentiation-dependent change of fatty
      acid profile during differentiation of mesenchymal stem cells to hepatocyte-like
      cells.
AB  - Differentiation of mesenchymal stem cells (MSCs) to hepatocyte-like cells is
      associated with morphological and biological changes. In this study, the effect
      of hepatogenic differentiation on fatty acid profile and the expression of
      proliferator-activated receptors-alpha (PPAR-alpha) have been studied. For this
      purpose, MSCs isolated from human umbilical cord were differentiated into
      hepatocyte-like cells on selective culture media. The morphological and
      biochemical changes, PPAR-alpha expression and reactive oxygen species (ROS)
      levels were studied during the differentiation process. Besides, the cells were
      processed to determine changes in fatty acid profile using gas chromatography
      analysis. The results showed that hepatic differentiation of the MSCs is
      associated with a decrease in major polyunsaturated fatty acids in mature
      hepatocytes, whereas there was an increase in the saturated fatty acid (SFA)
      levels during hepatocyte maturation. The differentiation-dependent shift in the
      ratio of SFA/USFA was associated with changes in albumin and PPAR-alpha
      expression, whereas changes in fatty acid profile were independent of ROS
      production and lipid peroxidation in differentiating cells. In conclusion, these
      data may suggest that hepatocyte formation during the stem cell differentiation
      is associated with a shift in the fatty acid profile that is probably a normal
      phenomenon in hepatogenic differentiation of the MSCs.

PMID- 24585389
TI  - Lyophilized silica lipid hybrid (SLH) carriers for poorly water-soluble drugs:
      physicochemical and in vitro pharmaceutical investigations.
AB  - Lyophilization was investigated to produce a powdery silica-lipid hybrid (SLH)
      carrier for oral delivery of poorly water-soluble drugs. The silica to lipid
      ratio, incorporation of cryoprotectant, and lipid loading level were investigated
      as performance indicators for lyophilized SLH carriers. Celecoxib, a nonsteroidal
      anti-inflammatory drug, was used as the model poorly soluble moiety to attain
      desirable physicochemical and in vitro drug solubilization properties. Scanning
      electron microscopy and confocal fluorescence imaging verified a nanoporous,
      homogenous internal matrix structures of the lyophilized SLH particles, prepared
      from submicron triglyceride emulsions and stabilized by porous silica
      nanoparticles (Aerosil 380), similar to spray-dried SLH. 20-50 wt % of silica in
      the formulation have shown to produce nonoily SLH agglomerates with complete
      lipid encapsulation. The incorporation of a cryoprotectant prevented irreversible
      aggregation of the silica-stabilized droplets during lyophilization, thereby
      readily redispersing in water to form micrometre-sized particles (<5 MUm). The
      lyophilized SLH produced approximately 1.5-fold and fivefold increased drug
      solubilization than the pure drug under nondigesting and digesting conditions,
      respectively. The feasibility of lyophilization for producing nanostructured SLH
      formulations with desirable lipid loading and drug solubilization properties for
      enhanced oral delivery of poorly water-soluble therapeutics is confirmed.

PMID- 24585390
TI  - The role of TET family proteins and 5-hydroxymethylcytosine in human tumors.
AB  - Tumorigenesis correlates with hypermethylation of tumor suppressors and
      hypomethylation of oncogenes. DNA methyltransferases (DNMTs) catalyze DNA
      methylation, and mutations and aberrant expression in DNMT genes are found in
      multiple human tumors. The discovery of the DNA demethylation function of TET
      proteins has opened up new avenues for the study of DNA methylation regulation.
      TET proteins regulate the DNA demethylation pathway through oxidizing 5-mC into 5
      hmC, 5-fC, and 5-aC. TET genes have been reported to be frequently mutated in
      hematopoietic malignancies and are associated with the malignant transformation
      of cells. Loss-of-function mutations in TET genes have not been reported in human
      solid tumors. However, 5-hmC has been found to be reduced in various solid
      tumors, indicating that TET genes may contribute to cellular transformation via
      regulation of DNA demethylation. As a new epigenetic modification, 5-hmC may be a
      useful biomarker for the diagnosis of cancers. To better understand the roles of
      TET and 5-hmC in tumors, the biological functions of TET and 5-hmC should be
      studied further.

PMID- 24585391
TI  - Resilience and vulnerability in adolescents: genetic influences on differential
      response to risk for delinquency.
AB  - Prior research has identified a vast number of correlates for delinquent behavior
      during adolescence, yet a considerable number of errors in prediction remain.
      These errors suggest that behavioral development among a portion of youths is not
      well understood, with some exhibiting resilience and others a heightened
      vulnerability to risks. Examining cases that do not confirm prediction outcomes
      provides an opportunity to achieve a greater understanding of the relationships
      between risk factors and delinquency, which can be used to improve theoretical
      explanations of behavior. This study explores the contribution of genetic and
      environmental factors to differences in individual responses to cumulative risk
      for delinquency among a sample of adolescent twins (N = 784 pairs, 49 % female)
      in the National Longitudinal Study of Adolescent Health. The results indicate
      that additive genetic and unique environmental factors significantly contribute
      to variation in responses to cumulative risk across 14 risk factors spanning
      individual, familial, and environmental domains. When analyzed separately, the
      majority of the difference between vulnerable youths and the overall population
      was attributed to genetic influences, while differences between resilient youths
      and the population were primarily attributed to environmental influences. The
      findings illustrate the importance of examining both genetic and environmental
      influences in order to enhance explanations of adolescent offending. 

PMID- 24585392
TI  - Psychometric properties of the Revised Chen Internet Addiction Scale (CIAS-R) in
      Chinese adolescents.
AB  - The Revised Chen Internet Addiction Scale (CIAS-R) was developed to assess
      Internet addiction in Chinese populations, but its psychometric properties in
      adolescents have not been examined. This study aimed to evaluate the factor
      structure and psychometric properties of CIAS-R in Hong Kong Chinese adolescents.
      860 Grade 7 to 13 students (38 % boys) completed the CIAS-R, the Young's Internet
      Addiction Test (IAT), and the Health of the Nation Outcome Scales for Children
      and Adolescents (HoNOSCA) in a survey. The prevalence of Internet addiction as
      assessed by CIAS-R was 18 %. High internal consistency and inter-item
      correlations were reported for the CIAS-R. Results from the confirmatory factor
      analysis suggested a four-factor structure of Compulsive Use and Withdrawal,
      Tolerance, Interpersonal and Health-related Problems, and Time Management
      Problems. Moreover, results of hierarchical multiple regression supported the
      incremental validity of the CIAS-R to predict mental health outcomes beyond the
      effects of demographic differences and self-reported time spent online. The CIAS
      is a reliable and valid measure of internet addiction problems in Hong Kong
      adolescents. Future study is warranted to validate the cutoffs of the CIAS-R for
      identification of adolescents with Internet use problems who may have mental
      health needs. 

PMID- 24585395
TI  - [Infection-related root resorption].

PMID- 24585394
TI  - Twin reversed arterial perfusion (TRAP) sequence--does monoamniocity preclude
      early intervention?

PMID- 24585393
TI  - Longitudinal field studies of avian metapneumovirus and turkey hemorrhagic
      enteritis virus in turkeys suffering from colibacillosis associated mortality.
AB  - The aim of this study was to evaluate if the exposure to Avian metapneumovirus
      (aMPV) and/or to Turkey hemorrhagic enteritis virus (THEV) was significant for
      the induction of episodes of colibacillosis in aMPV and THEV vaccinated turkeys.
      Colibacillosis-associated mortality was recorded and longitudinal virological
      studies performed in three consecutive turkey flocks reared in the same farm.
      aMPV and THEV diagnostic swabs and blood samples were made once a week up to 14
      weeks of age. Swabs were processed by molecular techniques for viruses detection
      and antibody titres were evaluated. Field subtype B aMPVs were detected in all
      flocks at different ages of life always associated with respiratory signs and
      increase of colibacillosis-associated mortality. THEV has been consistently
      detected in all flocks since the 9th week of age. Vaccination with a single dose
      of the THEV commercial inactivated vaccine available in Italy seems does not
      protect the birds from the infection. Sequence comparison of the hexon protein of
      one of the THEV strains detected, and strains isolated worldwide, revealed high
      similarity between them. These results are consistent with the notion that the
      hexon protein, being the major antigenic component of the virus, is highly
      conserved between the strains. Results showed that field aMPV infection is
      directly correlated to colibacillosis-associated mortality. Less clear appears
      the role of THEV because the endemicity of aMPV makes difficult to evaluate its
      role in predisposing colibacillosis in absence of aMPV. It would be interesting
      to further investigate this issue through experimental trials in secure isolation
      conditions. 

PMID- 24585396
TI  - Serum Zn levels and Cu/Zn ratios worsen in hemodialysis patients, implying
      increased cardiovascular risk: a 2-year longitudinal study.
AB  - The objective of this study was to analyze serum Zn and Cu concentrations and
      Cu/Zn ratios in 116 hemodialysis patients (HPs) over a 2-year longitudinal study
      at four time points (6-month intervals). The relation exerted on these values by
      26 biochemical and nutritional indexes, the age and drug consumption of the
      patients, and the etiology of their disease were also evaluated. A healthy
      control group (n = 50) was also studied. Mean serum Zn concentrations were lower
      (p = 0.009) and the Cu/Zn ratios higher (p = 0.009) in HPs than in controls.
      Serum Cu levels in HP did not differ to those of controls. At all four sampling
      times, the mean serum Zn levels and Cu/Zn ratios were lower and higher,
      respectively, in HPs than in the controls. There was a significant reduction in
      serum Zn levels and an increase in Cu concentrations and Cu/Zn ratios in HPs from
      the second to the fourth sampling. Serum Zn levels of the HPs diminish with age
      older than 50 years. Serum Cu levels were significantly higher in patients
      consuming antihypercalcemic or anti-infarction drugs, whereas serum Cu levels and
      Cu/Zn ratios were significantly lower in those treated with diuretics. Diminished
      Zn levels were negatively correlated with low-density lipoprotein (LDL)
      cholesterol in HPs; however, enhanced Cu/Zn ratios were positively correlated
      with total cholesterol and LDL cholesterol. Both findings indicate an increased
      cardiovascular risk. We conclude that this study contributes the first evidence
      of a correlation between marked dyslipidemia and worsened Cu/Zn ratios in HPs,
      implying an increased risk of diseases associated with elevated oxidative stress,
      inflammation, and depressed immune function, such as cardiovascular diseases.

PMID- 24585397
TI  - Stereomicroscopic imaging technique for the quantification of cold flow in drug
      in-adhesive type of transdermal drug delivery systems.
AB  - Cold flow is a phenomenon occurring in drug-in-adhesive type of transdermal drug
      delivery systems (DIA-TDDS) because of the migration of DIA coat beyond the edge.
      Excessive cold flow can affect their therapeutic effectiveness, make removal of
      DIA-TDDS difficult from the pouch, and potentially decrease available dose if any
      drug remains adhered to pouch. There are no compendial or noncompendial methods
      available for quantification of this critical quality attribute. The objective
      was to develop a method for quantification of cold flow using stereomicroscopic
      imaging technique. Cold flow was induced by applying 1 kg force on punched-out
      samples of marketed estradiol DIA-TDDS (model product) stored at 25 degrees C, 32
      degrees C, and 40 degrees C/60% relative humidity (RH) for 1, 2, or 3 days. At
      the end of testing period, dimensional change in the area of DIA-TDDS samples was
      measured using image analysis software, and expressed as percent of cold flow.
      The percent of cold flow significantly decreased (p < 0.001) with increase in
      size of punched-out DIA-TDDS samples and increased (p < 0.001) with increase in
      cold flow induction temperature and time. This first ever report suggests that
      dimensional change in the area of punched-out samples stored at 32 degrees
      C/60%RH for 2 days applied with 1 kg force could be used for quantification of
      cold flow in DIA-TDDS.

PMID- 24585399
TI  - Patient versus professional based psychosocial risk factor screening for adverse
      pregnancy outcomes.
AB  - To identify Psychopathology, Psychosocial problems and substance use (PPS) as
      predictors of adverse pregnancy outcomes, two screen-and-advice instruments were
      developed: Mind2Care (M2C, self-report) and Rotterdam Reproductive Risk Reduction
      (R4U, professional's checklist). To decide on the best clinical approach of these
      risks, the performance of both instruments was compared. Observational study of
      164 pregnant women who booked at two midwifery practices in Rotterdam. Women were
      consecutively screened with M2C and R4U. For referral to tailored care based on
      specific PPS risks, inter-test agreement of single risks was performed in terms
      of overall accuracy and positive accuracy (risk present according to both
      instruments). With univariate regression analysis we explored determinants of
      poor agreement (<90 %). For triage based on risk accumulation and for detecting
      women-at-risk for adverse birth outcomes, M2C and R4U sum scores were compared.
      Overall accuracy of single risks was high (mean 93 %). Positive accuracy was
      lower (mean 46 %) with poorest accuracy for current psychiatric symptoms.
      Educational level and ethnicity partly explained poor accuracy (p < 0.05).
      Overall low PPS prevalence decreased the statistical power. For triage, M2C and
      R4U sum scores were interchangeable from sum scores of five or more (difference
      <1 %). The probability of adverse birth outcomes similarly increased with risk
      accumulation for both instruments, identifying 55-75 % of women-at-risk. The self
      report M2C and the professional's R4U checklist seem interchangeable for triage
      of women-at-risk for PPS or adverse birth outcomes. However, the instruments seem
      to provide complementary information if used as a guidance to tailored risk
      specific care.

PMID- 24585400
TI  - Physical activity and health-related quality of life during pregnancy: a
      secondary analysis of a cluster-randomised trial.
AB  - The aim of the study was to evaluate the role of physical activity before and
      during pregnancy on health-related quality of life (HRQoL). Data from the cluster
      randomised gestational diabetes mellitus primary prevention trial conducted in
      maternity clinics were utilised in a secondary analysis. The cases considered
      were pregnant women who reported engaging in at least 150 min of moderate
      intensity leisure-time physical activity per week (active women) (N = 80), and
      the controls were women below these recommendations (less active) (N = 258). All
      participants had at least one risk factor for gestational diabetes mellitus.
      Their HRQoL was evaluated via the validated generic instrument 15D, with HRQoL at
      the end of pregnancy examined in relation to changes in physical activity during
      pregnancy. Logistic regression models addressed age, parity, education, and pre
      pregnancy body mass index. At the end of pregnancy, the expected HRQoL was higher
      (tobit regression coefficient 0.022, 95 % CI 0.003-0.042) among active women than
      less active women. Active women also had greater mobility (OR 1.98, 95 % CI 1.04
      3.78), ability to handle their usual activities (OR 2.22, 95 % CI 1.29-3.81), and
      vitality (OR 2.08, 95 % CI 1.22-3.54) than did less active women. Active women
      reported higher-quality sleep (OR 2.11, 95 % CI 1.03-4.30) throughout pregnancy
      as compared to less active women. Meeting of the physical activity guidelines
      before pregnancy was associated with better overall HRQoL and components thereof
      related to physical activity.

PMID- 24585401
TI  - Familiarity of physicians, translational researchers, nurses, and other health
      professionals with evidence-based medicine terms and resources.
AB  - Evidence-based medicine (EBM) is a central theme in health practice and training.
      The understanding of EBM technical terms and the familiarity with EBM resources
      were surveyed in four different health professional categories. A self
      administered questionnaire on the familiarity with EBM terminology and resources
      was proposed to 218 health professionals (physicians, translational researchers,
      nurses, and others) working in the oncology field. Relationships between variable
      and familiarity were examined: Pearson chi(2) or exact Fisher test was used for
      the categorical variables and one-way ANOVA for the continuous ones. The odds of
      familiarity for subjects, who had followed or not at least one EBM course, were
      estimated fitting a multiple logistic regression model adjusted for age, gender,
      and profession. All subjects completed the questionnaire. The majority of health
      personnel seemed to lack a sound knowledge of key EBM terms and sources.
      Physicians showed the highest knowledge of terms, nurses the lowest. Physicians
      also declared the largest familiarity with the widest variety of resources,
      followed by others and the researchers. The most popular resource was PLNG, the
      Italian Guideline System. People who attended at least one EBM course showed
      consistently higher percentages of knowledge, but the association was irrelevant
      for nurses. The main perceived barrier to implement EBM in practice was a lack of
      personal time. Familiarity of health professionals with EBM terminology and
      resources is still limited to the medical field and needs to be improved.
      Increasing education may be pivotal, even if different approaches should be
      developed for different professional categories.

PMID- 24585398
TI  - Household food insecurity, maternal nutritional status, and infant feeding
      practices among HIV-infected Ugandan women receiving combination antiretroviral
      therapy.
AB  - Household food insecurity (HHFI) may be a barrier to both optimal maternal
      nutritional status and infant feeding practices, but few studies have tested this
      relationship quantitatively, and never among HIV-infected individuals. We
      therefore described the prevalence of HHFI and explored if it was associated with
      poorer maternal nutritional status, shorter duration of exclusive breastfeeding
      (EBF) and fewer animal-source complementary foods. We assessed these outcomes
      using bivariate and multivariate analyses among 178 HIV-infected pregnant and
      breastfeeding (BF) women receiving combination antiretroviral therapy in the
      PROMOTE trial (NCT00993031), a prospective, longitudinal cohort study in Tororo,
      Uganda. HHFI was common; the prevalence of severe, moderate, and little to no
      household hunger was 7.3, 39.9, and 52.8 %, respectively. Poor maternal
      nutritional status was common and women in households experiencing moderate to
      severe household hunger (MSHH) had statistically significantly lower body mass
      index (BMIs) at enrollment (21.3 vs. 22.5, p < 0.01) and prior to delivery (22.6
      vs. 23.8, p < 0.01). BMI across time during pregnancy, but not gestational weight
      gain, was significantly lower for MSHH [adjusted beta (95 % CI) -0.79 (-1.56, 
      0.02), p = 0.04; -2.06 (-4.31, 0.19), p = 0.07], respectively. The prevalence (95
      % CI) of EBF at 6 months was 67.2 % (59.7-73.5 %), and the proportion of women BF
      at 12 months was 80.4 % (73.3-85.7 %). MSHH was not associated with prevalence of
      EBF at 6 months or BF at 12 months. However, among those women still EBF at 4
      months (81.4 % of population), those experiencing MSHH were significantly more
      likely to cease EBF between 4 and 6 months (aHR 2.38, 95 % CI 1.02-5.58). The
      prevalence of HHFI, maternal malnutrition, and suboptimal infant feeding
      practices are high and the causal relationships among these phenomena must be
      further explored.

PMID- 24585402
TI  - Synthesis and biological evaluation of substituted N-[3-(1H-pyrrol-1-yl)methyl]
      1,2,5,6-tetrahydropyridin-1-yl]benzamide/benzene sulfonamides as anti
      inflammatory agents.
AB  - The pharmacological activities of tetrahydropyridine (THP) derivatives are
      dependent on the substituent ring moiety. In this study, we investigate the anti
      inflammatory activities of 12 newly synthesized substituted N-[3-(1H-pyrrol-1
      yl)methyl]-1,2,5,6-tetrahydrobenzamide/benzene sulfonamides (9a-l) in murine BV-2
      microglial cells. All compounds were initially screened for attenuation of nitric
      oxide (NO) production in lipopolysaccharide (LPS) (1 ug/mL)-activated microglial
      cells. The data show that only SO2 -substituted THPs were effective at sub-lethal
      concentrations (IC50 values of 12.92 uM (9i), 14.64 uM (9j), 19.63 uM (9k))
      relative to L-N6-(1-iminoethyl)lysine positive control (IC50  = 3.1 uM). The most
      potent SO2 -substituted compound (9i) also blocked the LPS-inducible nitric oxide
      synthase (iNOS) and attenuated the release of several cytokines including IL
      1alpha, IL-10, and IL-6. These findings establish the moderate immuno-modulating
      effects of SO2 -substituted THP derivatives. 

PMID- 24585404
TI  - Histopathology and pathogenesis of caerulein-, duct ligation-, and arginine
      induced acute pancreatitis in Sprague-Dawley rats and C57BL6 mice.
AB  - Three classical rodent models of acute pancreatitis were created in an effort to
      identify potential pre-clinical models of drug-induced pancreatitis (DIP) and
      candidate non-invasive biomarkers for improved detection of DIP. Study objectives
      included designing a lexicon to minimize bias by capturing normal variation and
      spontaneous and injury-induced changes while maintaining the ability to
      statistically differentiate degrees of change, defining morphologic anchors for
      novel pancreatic injury biomarkers, and improved understanding of mechanisms
      responsible for pancreatitis. Models were created in male Sprague-Dawley rats and
      C57BL6 mice through: 1) administration of the cholecystokinin analog, caerulein;
      2) administration of arginine; 3) surgical ligation of the pancreatic duct. Nine
      morphologically detectable processes were used in the lexicon; acinar cell
      hypertrophy; acinar cell autophagy; acinar cell apoptosis; acinar cell necrosis;
      vascular injury; interstitial edema, inflammation and hemorrhage; fat necrosis;
      ductal changes; acinar cell atrophy. Criteria were defined for scoring levels (0
      = absent, 1 = mild, 2 = moderate, 3 = severe) for each lexicon component.
      Consistent with previous studies, histopathology scores were significant greater
      in rats compared to mice at baseline and after treatment. The histopathology
      scores in caerulein and ligation-treated rats and mice were significantly greater
      than those of arginine-treated rats and mice. The present study supports a
      multifaceted pathogenesis for acute pancreatitis in which intra-acinar
      trypsinogen activation, damage to acinar cells, fat cells, and vascular cells as
      well as activation/degranulation of mast cells and activated macrophages all
      contribute to the initiation and/or progression of acute inflammation of the
      exocrine pancreas.

PMID- 24585405
TI  - Profiling of autoantibodies in sera of pancreatic cancer patients.
AB  - BACKGROUND: Although autoantibodies to cancer antigens are candidates for
      biomarkers, no comprehensive studies to detect cancer-specific antibodies have
      been performed. This study identified autoantibodies in the sera of pancreatic
      cancer (PC) patients using proteomics based on a wheat germ cell-free protein
      production system. METHODS: We constructed a biotinylated protein library of
      2,183 genes. Interactions between biotinylated proteins and serum antibodies were
      detected by AlphaScreen(r) assay. Relative luminescence signals of each protein
      in 37 PC patients and 20 healthy controls were measured, and their sensitivity
      and specificity for PC were calculated. RESULTS: Luminescence signals of nine
      proteins were significantly higher than those of healthy controls, with calcium
      and integrin binding 1 (CIB1) protein showing the greatest significance (p =
      0.002). Sensitivity, specificity, positive predictive value and negative
      predictive value of CIB1 autoantibody alone for PC were 76, 70, 82, and 61 %,
      respectively, and 97, 35, 74, and 88 %, respectively, when the four most
      significant proteins were combined. Presence of these autoantibodies did not vary
      significantly with other clinicopathological characteristics. CONCLUSION: Several
      autoantibodies, including CIB1, are potential biomarkers for PC.

PMID- 24585403
TI  - Quantification of liver iron with MRI: state of the art and remaining challenges.
AB  - Liver iron overload is the histological hallmark of hereditary hemochromatosis
      and transfusional hemosiderosis, and can also occur in chronic hepatopathies.
      Iron overload can result in liver damage, with the eventual development of
      cirrhosis, liver failure, and hepatocellular carcinoma. Assessment of liver iron
      levels is necessary for detection and quantitative staging of iron overload and
      monitoring of iron-reducing treatments. This article discusses the need for
      noninvasive assessment of liver iron and reviews qualitative and quantitative
      methods with a particular emphasis on magnetic resonance imaging (MRI). Specific
      MRI methods for liver iron quantification include signal intensity ratio as well
      as R2 and R2* relaxometry techniques. Methods that are in clinical use, as well
      as their limitations, are described. Remaining challenges, unsolved problems, and
      emerging techniques to provide improved characterization of liver iron deposition
      are discussed.

PMID- 24585406
TI  - Pemetrexed-carboplatin adjuvant chemotherapy with or without gefitinib in
      resected stage IIIA-N2 non-small cell lung cancer harbouring EGFR mutations: a
      randomized, phase II study.
AB  - BACKGROUND: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR
      TKIs) show great efficacy in patients with advanced non-small cell lung cancer
      (NSCLC) with EGFR mutations. The efficacy and safety of gefitinib following
      adjuvant chemotherapy in patients with EGFR mutation are unknown. METHODS: In
      this open-label, phase II study, patients with resected stage IIIA-N2 NSCLC
      harbouring EGFR mutations (either exon 19 deletion or L858R point mutation) were
      assigned randomly to receive pemetrexed (500 mg/m(2)) and carboplatin (AUC = 5),
      administered every 21 days for 4 cycles, followed with or without gefitinib (250
      mg/day) for 6 months. The primary end point was disease-free survival (DFS).
      RESULTS: From August 2008 to September 2011, 60 patients were included in our
      center. DFS was significantly longer among those who received pemetrexed and
      carboplatin (PC)-gefitinib than among those who received PC alone [hazard ratio
      (HR), 0.37; 95 % confidence interval (CI) 0.16-0.85; P = 0.014; median, 39.8 vs.
      27.0 months]. The rates of 2-year DFS were 78.9 % in the PC-gefitinib group and
      54.2 % in the PC alone group. The rates of 2-year overall survival (OS) were 92.4
      % in the PC-gefitinib group and 77.4 % in the PC alone group (HR, 0.37; 95 % CI
      0.12-1.11, P = 0.076). The most common adverse event was rash (43.3 %, 13/30) in
      the PC-gefitinib group and the administration of gefitinib following chemotherapy
      was well tolerated. CONCLUSIONS: The administration of gefitinib following PC
      adjuvant therapy shows significant improvement in DFS in patients with resected
      stage IIIA-N2 NSCLC harbouring EGFR mutations.

PMID- 24585407
TI  - Predictors and outcomes of completion axillary node dissection among older breast
      cancer patients.
AB  - BACKGROUND: The role of completion axillary lymph node dissection (ALND) for
      older women who had sentinel lymph node-positive (SLN+) invasive breast cancer is
      unclear. We examined factors predictive of ALND and the association between ALND,
      adjuvant chemotherapy administration, and survival. METHODS: Using the
      Surveillance, Epidemiology, and End Results (SEER)-Medicare database, we reviewed
      records of women age >65 diagnosed with stage I/II breast cancer from 1998-2005.
      Adjusted Cox proportional hazards and multivariate logistic regression were used
      to identify patient and disease variables associated with ALND, and assess
      association between ALND and all-cause and breast cancer-specific survival.
      RESULTS: Among SLN+ patients, 88 % underwent ALND. Earlier diagnosis year,
      greater nodal involvement, younger age, registry location, and larger tumor size
      were all associated with a significantly higher likelihood of ALND. The ALND in
      SLN+ patients was not significantly associated with 5-year breast cancer-specific
      survival (hazard ratio [HR] 1.22, 95 % confidence interval [CI] 0.76-1.96). The
      SLN+ patients who underwent ALND were more likely to receive adjuvant
      chemotherapy (odds ratio [OR] 1.8, 95 % CI 1.45-2.24). However, younger age (OR
      18.0, 95 % CI 14.4-23.9), estrogen receptor-negative (ER-) status (OR 4.2, 95 %
      CI 3.4-5.3), and fewer comorbidities (OR 2.6, 95 % CI 1.7-4.0) were all more
      strongly linked to receipt of chemotherapy. CONCLUSIONS: ALND for older patients
      with SLN+ breast cancer is not associated with improved 5-year all-cause or
      breast cancer-specific survival. Younger age, fewer comorbidities, and estrogen
      receptor-negative (ER-) status were more strongly associated with receipt of
      chemotherapy than ALND. Consideration should be given to omitting ALND in older
      patients, particularly if findings of ALND will not influence adjuvant therapy
      decisions.

PMID- 24585408
TI  - Major reduction in 30-day mortality after elective colorectal cancer surgery: a
      nationwide population-based study in Denmark 2001-2011.
AB  - BACKGROUND: For years, the outcome of colorectal cancer (CRC) surgery has been
      inferior in Denmark compared to its neighbouring countries. Several strategies
      have been initiated in Denmark to improve CRC prognosis. We studied whether there
      has been any effect on postoperative mortality based on the information from a
      national database. METHODS: Patients who underwent elective major surgery for CRC
      in the period 2001-2011 were identified in the national Danish Colorectal Cancer
      Group database. Thirty-day mortality rates were calculated and factors with
      impact on mortality were identified using logistic regression analysis. RESULTS:
      In total, 27,563 patients underwent elective major surgery and their 30-day
      mortality rate decreased significantly from 7.3 % in 2001-2002 to 2.8 % in 2011
      (P < 0.001). Aside from the year of surgery, independent risk factors of
      mortality were male gender, age >= 61 years, American Society of
      Anesthesiologists score >= II, tumor located in the colon, palliative intent,
      outcome of surgery "not cured," and open surgical approach. Additionally, 3-month
      mortality of all 37,022 CRC patients, irrespective of surgical treatment,
      decreased significantly from 15.8 to 11.3 % during the study period. CONCLUSION:
      The 30-day mortality rate after elective major surgery for CRC has decreased
      significantly in Denmark in the past decade. Laparoscopic surgical approach was
      associated with a reduction in mortality in colon cancer.

PMID- 24585409
TI  - No association of plasma levels of adiponectin and c-peptide with risk of
      aggressive prostate cancer in the Cancer Prevention Study II Nutrition Cohort.
AB  - BACKGROUND: Obesity is associated with a higher risk of aggressive prostate
      cancer and alters circulating levels of insulin and adiponectin, two hormones
      that influence biologic processes implicated in carcinogenesis. Results of some
      studies showed associations of circulating levels of adiponectin, insulin, and c
      peptide (a marker of insulin secretion) with aggressive prostate cancer, but the
      size of these studies was limited. METHODS: A nested case-control study of 272
      aggressive prostate cancer cases [Gleason score >= 7 (4+3) or T3-T4] and 272 age-
      and race-matched controls from the Cancer Prevention Study II Nutrition Cohort
      was conducted to determine the associations of prediagnostic plasma levels of c
      peptide and adiponectin with risk of aggressive prostate cancer. RESULTS: Neither
      circulating adiponectin nor c-peptide was associated with risk of aggressive
      prostate cancer. In analyses of the highest-risk aggressive prostate cancer
      (Gleason score >= 8 or T3-T4), the highest quartile of c-peptide, compared with
      the lowest, was associated with an OR of 1.41 [95% confidence interval (CI), 0.72
      2.78]. CONCLUSIONS: Our findings provide no support for the hypothesis that
      adiponectin is associated with risk of aggressive prostate cancer but a possible
      association of high levels of c-peptide with particularly high-risk prostate
      cancer cannot be ruled out. IMPACT: These results indicate that changes in
      circulating levels of adiponectin and c-peptide do not play an important role in
      risk of aggressive prostate cancer.

PMID- 24585410
TI  - Beals syndrome (congenital contractural arachnodactyly): prenatal ultrasound
      findings and molecular analysis.
AB  - We report the prenatal findings in two cases of Beals syndrome. Both pregnancies
      presented with clinical features of arthrogryposis multiplex congenita/fetal
      akinesia syndrome (AMC/FAS), including clenched fists and multiple joint
      contractures on repeat prenatal ultrasound examinations. The first case was
      diagnosed as having Beals syndrome on physical examination shortly after birth
      and the diagnosis was confirmed by DNA analysis, shown as a point mutation in the
      fibrillin 2 (FBN2) gene. The second case was diagnosed with Beals syndrome
      following microarray analysis on amniocytes, which showed a deletion of the FBN2
      gene. Although most cases with AMC/FAS carry a poor prognosis, Beals syndrome is
      consistent with normal cognitive development and a better prognosis. Thus, making
      the correct diagnosis is crucial, both pre- and postnatally, for accurate
      counseling and management.

PMID- 24585411
TI  - Maternal exposure to fine particulate pollution during narrow gestational periods
      and newborn health in Harris County, Texas.
AB  - It remains unclear when the fetus is most susceptible to the effects of
      particulate air pollution. We conducted a population-based study in a large urban
      area to evaluate associations between preterm birth (PTB) and fetal growth and
      exposures to fine particles (PM(2.5)) during narrow periods of gestation. We
      identified 177,816 births during 2005-2007 among mothers who resided in Harris
      County, Texas at the time of delivery. We created three mutually exclusive
      categories of mildly (33-36 completed weeks of gestation), moderately (29-32
      weeks of gestation), and severely (20-28 weeks of gestation) PTB, and among full
      term infants, we identified those who were born small for their gestational age.
      Using routine air monitoring data, we generated county-level daily time series of
      estimated ambient air levels of PM2.5 and then computed exposure metrics during
      every 4 weeks of a mother's pregnancy. We evaluated associations in each 4-week
      period using multiple logistic regression. A 10 MUg/m(3) increase in PM(2.5)
      exposure in the first 4 weeks of pregnancy significantly increased the odds of
      mildly, moderately and severely PTB by 16, 71 and 73 %, respectively.
      Associations were stronger when infants with birth defects were excluded. Our
      findings indicate an association between PM(2.5) and PTB, with stronger
      associations for moderately and severely PTB infants. Efforts should continue to
      implement stricter air quality standards and improve ambient air quality.

PMID- 24585412
TI  - Assessing patient experiences in the pediatric patient-centered medical home: a
      comparison of two instruments.
AB  - The Patient-Centered Medical Home (PCMH) is a model of care that has been
      promoted as a way to transform a broken primary care system in the US. However,
      in order to convince more practices to make the transformation and to properly
      reimburse practices who are PCMHs, valid and reliable data are needed. Data that
      capture patient experiences in a PCMH is valuable, but which instrument should be
      used remains unclear. Our study aims to compare the validity and reliability of
      two national PCMH instruments. Telephone surveys were conducted with children who
      receive care from 20 pediatric practices across Florida (n = 990). All of the
      children are eligible for Medicaid or the Children's Health Insurance Program.
      Analyses were conducted to compare the Consumer Assessment of Health Plan Survey
      Patient-Centered Medical Home (CAHPS-PCMH) and the National Survey of Children
      with Special Health Care Needs (NS-CSHCN) medical home domain. Respondents were
      mainly White non-Hispanic, female, under 35 years old, and from a two-parent
      household. The NS-CSHCN outperformed the CAHPS-PCMH in regard to scale
      reliability (Cronbach's alpha coefficients all >=0.81 vs. 0.56-0.85,
      respectively). In regard to item-domain convergence and discriminant validity the
      CAHPS-PCMH fared better than the NS-CSHCN (range of convergence 0.66-0.93 vs.
      0.32-1.00). The CAHPS-PCMH did not correspond to the scale structure in construct
      validity testing. Neither instrument performed well in the known-groups validity
      tests. No clear best instrument was determined. Further revision and calibration
      may be needed to accurately assess patient experiences in the PCMH.

PMID- 24585414
TI  - Early life epigenetic programming and transmission of stress-induced traits in
      mammals: how and when can environmental factors influence traits and their
      transgenerational inheritance?
AB  - The environment can have a long-lasting influence on an individual's physiology
      and behavior. While some environmental conditions can be beneficial and result in
      adaptive responses, others can lead to pathological behaviors. Many studies have
      demonstrated that changes induced by the environment are expressed not only by
      the individuals directly exposed, but also by the offspring sometimes across
      multiple generations. Epigenetic alterations have been proposed as underlying
      mechanisms for such transmissible effects. Here, we review the most relevant
      literature on these changes and the developmental stages they affect the most. We
      discuss current evidence for transgenerational effects of prenatal and postnatal
      factors on bodily functions and behavioral responses, and the potential
      epigenetic mechanisms involved. We also discuss the need for a careful evaluation
      of the evolutionary importance with respect to health and disease, and possible
      directions for future research in the field. 

PMID- 24585413
TI  - The immunostimulatory effects of retinoblastoma cell supernatant on dendritic
      cells.
AB  - Dendritic cells (DCs) are crucial for the induction and maintenance of tumor
      specific immune responses. Studies have shown that tumor-associated DCs are
      immunosuppressed in some human tumors. However, phenotype and function of DCs in
      retinoblastoma (RB) remain unclear. RB cell supernatant (RBcs) was used to treat
      DCs in vitro to explore the effect of RB cells on DCs. DCs were generated from
      peripheral blood mononuclear cells of healthy donors. On day 5 of culture, DCs
      were treated with RBcs for 24 h, and then purified using magnetic beads. The
      maturation of DCs was induced by TNF-alpha or LPS. After treatment with RBcs,
      expression of co-stimulatory molecules CD80 and CD86 was elevated in DCs,
      accompanied by increased production of IL-12p70, TNF-alpha, IL-6, IL-1beta, and
      IL-8 but decreased production of IL-10. RBcs neither inhibited DC maturation nor
      promoted DC apoptosis. Moreover, RBcs-exposed DCs stimulated allogenetic T cell
      proliferation and T cell-derived cytokine production. These results indicate that
      RBcs can improve DCs' antigen presenting function and capability to activate T
      cells, suggesting that RB cells may have an immunostimulatory effect on DCs, and
      DC-based immunotherapy may be adopted in the treatment of RB.

PMID- 24585415
TI  - [Implants in contact with tissues other than bone. Is there room for a potential
      paradigm shift?].
AB  - RATIONALE: Modern dental implantology is now 30 year old. During this period of
      time, concepts have evolved and triggered several paradigm shifts. The aim of the
      present paper is to present a case treated with an innovative unconventional
      protocol. The latter is aimed to avoid invasive surgery when edentulism is caused
      by an impacted tooth. OBJECTIVES: The implant has been placed through the
      impacted canine and led, in addition to the classical implant-bone interface, to
      several other types of implant-tissue interface. RESULTS: Healing was uneventful;
      at the 1-year control, the implant was clinically integrated, the soft tissues
      around the final crown were satisfactory and the radiographic examination did not
      call any specific observation. CONCLUSIONS: Before endorsing this protocol in
      routine application, inclusion/exclusion criteria must be asserted and additional
      clinical cases with longer follow-up are warranted. Nonetheless, this
      unconventional protocol opens intriguing possibilities; it also suggests that
      there is still room to further revisit some of the leading concepts in dental
      implantology.

PMID- 24585416
TI  - Is there cerebellar pathology in essential tremor?

PMID- 24585417
TI  - A 24-week pegylated interferon alpha-2b versus a 12-week pegylated interferon
      alpha-2b alone or with ribavirin for patients with acute hepatitis C.

PMID- 24585418
TI  - Authors' response re: Petros, P. 2014, Urethral resistance to flow, not pressure,
      is the prime determinant of continence. Neurourol Urodyn.

PMID- 24585419
TI  - [Digital implant impression taking - an overview].
AB  - In dentist's daily practice, intraoral scanning systems are increased. Besides
      scanning of prepared teeth, also implants could be scanned intraorally. This
      clinical report describes the step-by-step techniques to scan digitally intraoral
      implants with two intraoral scanners (LavaTM C.O.S., 3M Espe and the CEREC AC
      connected with inLab MC XL, Sirona) for generating implant suprastructures
      without the use of impression materials, dental stone or implant impression
      copings. Different workflows, possibilities and limits by scanning dental
      implants are demonstrated.

PMID- 24585420
TI  - Predictive value of cardiovascular parameters in twin-to-twin transfusion
      syndrome.
AB  - OBJECTIVE: To evaluate the prognostic value of the Children's Hospital Of
      Philadelphia (CHOP) cardiovascular score and the modified myocardial performance
      index (MPI), in determining the risk of recipient fetal loss in twin-to-twin
      transfusion syndrome (TTTS). METHODS: This cohort study was based on data
      collected prospectively from 105 pregnancies complicated by TTTS (Quintero stages
      I-IV) and treated with laser photocoagulation between May 2008 and February 2013.
      Fetuses underwent detailed anatomical and Doppler ultrasonography with cardiac
      assessment as part of routine care. CHOP score and right MPI were calculated and
      cut-offs selected using receiver-operating characteristics curve analysis. These
      were compared according to loss of recipient fetus, using univariate and
      multivariate logistic regression. The correlation between CHOP score, MPI and
      Quintero stage was determined and we investigated differences in MPI before and
      after laser coagulation in a cohort of 90 recipient fetuses. RESULTS: Rates of
      recipient fetal loss were significantly higher when the CHOP score was >= 3
      (39.5% vs 12.9%, P = 0.002) and when MPI z-score was > 1.645 (34.5% vs 10.6%, P =
      0.004). After adjustment for Quintero stage, the risk of recipient fetal loss
      remained significantly higher when the CHOP score was >= 3 (odds ratio, 3.09; 95%
      CI, 1.035-9.21). There was a positive correlation between CHOP score, MPI and
      Quintero stage. MPI was significantly lower after compared with before laser
      coagulation. CONCLUSION: CHOP score and MPI are predictors of recipient fetal
      loss in TTTS and may be used to supplement Quintero's classification.

PMID- 24585421
TI  - In response to "It's safety, not the score, that needs improvement".

PMID- 24585422
TI  - The influence of menopause on the development of hepatic fibrosis in nonobese
      women with nonalcoholic fatty liver disease.

PMID- 24585423
TI  - A comprehensive clinical study about patching after strabismus surgery.
AB  - PURPOSE: Patching of the operative eye is occasionally used in pediatric
      strabismus surgery. The primary purpose of this study was to investigate the
      psychological and physiologic effects of patching after operation by
      multifactorial methods. METHODS: We analyzed the perioperative behaviors of 61
      children with strabismus conducted from June 2012 to July 2013 in this
      prospective longitudinal study. The children were randomized into 2 groups.
      Patients in the patching group underwent postoperative patching and others
      received no patching. Main outcome measures included The Faces Pain Scale-Revised
      score or numerical rating scales score, Children's Hospital of Eastern Ontario
      Pain Scale (CHEOPS) score, crying time, and preoperative and postoperative
      physiologic parameters. RESULTS: Crying time was significantly longer in the
      patching group than in the no patching group, but self-report scores showed no
      difference in the groups. Repeated-measures analysis of variance on ranks
      revealed that postoperative CHEOPS score was lower in the no patching group than
      in the patching group, whereas no physiologic parameters were significantly
      different in the 2 groups. CONCLUSIONS: Patching is not necessary for reducing
      postoperative pain or the risk of infection in children undergoing strabismus
      surgery.

PMID- 24585424
TI  - Intravitreal bevacizumab combined with grid photocoagulation in recurrent macular
      edema secondary to retinal vein occlusion.
AB  - PURPOSE: To evaluate improvement in best-corrected visual acuity (BCVA) and the
      reduction of central retinal thickness (CRT) in patients with macular edema
      secondary to retinal vein occlusion (RVO) after intravitreal bevacizumab (IVB)
      injection combined with macular grid photocoagulation. METHODS: A retrospective
      study of 54 consecutive eyes with macular edema associated with RVO. The BCVA and
      CRT, recorded with spectral-domain optical coherence tomography, were evaluated
      at baseline and 1, 3, 6, and 12 months after treatment onset. Intravitreal
      bevacizumab injection was administered at baseline, and macular grid
      photocoagulation 15 days later. During follow-up, additional IVB, at 1-month
      intervals, was administered if persistent or recurrent macular edema was observed
      on optical coherence tomography. RESULTS: Best-corrected visual acuity was
      improved and CRT was reduced at 1, 3, 6, and 12 months of follow-up. Compared
      with initial values, the final CRT was significantly reduced in patients with
      branch RVO (35 patients) and in patients with central RVO (19 patients) (p<0.05).
      Also, BCVA was significantly improved in both groups of patients (p<0.05).
      CONCLUSIONS: Intravitreal bevacizumab injection combined with macular grid
      photocoagulation reduces recurrent macular edema associated with branch RVO and
      central RVO.

PMID- 24585425
TI  - Homozygous c.1937+1G>A splice-site variant of the ABCA4 gene is associated with
      Stargardt disease.
AB  - PURPOSE: To report the phenotype of homozygous ABCA4 c.1937+1G>A splice-site
      variant associated with Stargardt disease. METHODS: Two siblings, a 10-year-old
      boy and a 32-year-old woman, born from consanguineous parents, presented with
      central vision loss and macular pigmentary atrophic changes suggestive of
      Stargardt disease. After genetic counselling, ABCA4 gene analysis was performed.
      RESULTS: The 2 siblings affected were shown to be homozygous for the c.1937+1G>A
      splice junction variant of the ABCA4 gene. Both parents were heterozygous for the
      same mutation; they were asymptomatic and the fundus examination revealed a
      normal appearance. CONCLUSIONS: Thus far, ABCA4 c.1937+1G>A splice-site variant
      was shown to cause retinitis pigmentosa when in hemizygosity and Stargardt
      disease when present on one allele. In this family two sibs homozygous for the
      ABCA4 c.1937+1G>A splice-site variant have a less severe phenotype of Stargardt
      disease. This observation provides useful information for the diagnosis and
      counseling of patients with this ABCA4 variant.

PMID- 24585426
TI  - Acute suppurative bacterial dacryoadenitis: a rare case report.
AB  - PURPOSE: To describe a case of lacrimal gland abscess. METHODS: Case report.
      RESULTS: An 11-year-old boy with respiratory tract infection presented acutely
      with an enlarging, painful mass in the superotemporal fornix in his left eye.
      Clinical evaluation and computerized tomography scan of the orbit revealed a
      lacrimal gland abscess. Conjunctival swab and sputum grew Klebsiella pneumoniae.
      The child was treated with intravenous amikacin. CONCLUSIONS: Lacrimal gland
      abscess is a rare clinical entity. To our knowledge, this is the first reported
      case of Klebsiella pneumoniae-associated dacryoadenitis complicated by lacrimal
      gland abscess formation in a pediatric patient.

PMID- 24585427
TI  - Reconsidering the concept of behavioral mechanisms of drug action.
AB  - A half-century of research in behavioral pharmacology leaves little doubt that
      behavior-environment contingencies can determine the behavioral effects of drugs.
      Unfortunately, a coherent behavior-analytic framework within which to
      characterize the myriad ways in which contingencies interact with drugs, and to
      predict effects of a given drug under a given set of conditions, still has not
      developed. Some behavioral pharmacologists have suggested the concept of
      behavioral mechanisms of drug action as a foundation for such a framework. The
      notion of behavioral mechanisms, however, does not seem to have been fully
      embraced by behavioral pharmacologists. It is suggested here that one reason for
      this is that the concept itself has not been sufficiently clarified (i.e.,
      stimulus control over use of the phrase is not sufficiently precise).
      Furthermore, early behavioral pharmacologists may not have possessed an adequate
      set of analytic tools to develop a viable framework based upon behavior
      mechanisms. In the first part of this paper, the notion of behavioral mechanisms
      of drug action is explored, and the sort of data that might provide evidence of a
      behavioral mechanism is considered. In the second part, it is suggested that the
      increased availability of quantitative models in behavior analysis may help
      provide the tools needed for elucidating behavioral mechanisms of drug action.
      Some examples of how these models have been, and could be used are provided. 

PMID- 24585428
TI  - The tau of PSP: a long road to treatment.

PMID- 24585429
TI  - Inducible transient expression of Smpd3 prevents early lethality in fro/fro mice.
AB  - Sphingomyelin phosphodiesterase 3 (SMPD3) is a pleiotropic lipid metabolizing
      enzyme involved in multiple physiological processes. A deletion mutation in the
      murine Smpd3 gene called fragilitas ossium (fro) leads to severe skeletal
      abnormalities in the developing fro/fro embryos. Although fro/fro mice can be
      useful to study many different aspects of SMPD3 functions, their perinatal
      lethality makes it difficult to generate a sufficient number of mice for
      controlled studies. In fact, on the C57BL/6 genetic background, none of the
      fro/fro mice survive beyond the perinatal stage. In this study, we used the "Tet
      On" inducible gene expression system to express Smpd3 transiently in fro/fro;ROSA
      rtTA;TRE-Smpd3 embryos on the C57BL/6 background. This induced Smpd3 expression
      corrected all the skeletal abnormalities in these embryos and prevented their
      early death. However, induction of Smpd3 expression in the adolescent
      fro/fro;ROSA-rtTA;TRE-Smpd3 mice was not sufficient to correct the defects in
      trabecular bone mineralization and the impaired growth of the long bones. This
      novel mouse model will be a useful tool to study SMPD3 biology in vivo.

PMID- 24585431
TI  - Prevalence and natural history of histologically proven chronic liver disease in
      a longitudinal cohort of patients with type 1 diabetes.
AB  - Although a higher prevalence of raised liver enzymes and altered echotexture on
      ultrasound have been reported in patients with type 1 diabetes mellitus (T1DM),
      the histological spectrum and natural history of chronic liver disease (CLD) in
      T1DM is unknown. We investigated the prevalence and outcome of histologically
      proven CLD in a longitudinal cohort of patients with T1DM. We identified patients
      who have had liver biopsy from a computerized database (DIAMOND; Hicom
      Technology, Brookwood, UK) containing longitudinal data for over 95% of type 1
      diabetes patients from an overall catchment population of 700,000 people. Gender
      matched patients with oral hypoglycemic-treated (T2OH) and insulin-treated type 2
      diabetes (T2IN) who had liver biopsy formed two comparative cohorts. We collated
      clinical and histological data, as well as long-term outcomes of all three
      groups, and compared T1DM cirrhosis incidence to UK general population data. Of
      4,644 patients with T1DM, 57 (1.2%) underwent liver biopsy. Of these, 53.1% of
      patients had steatosis, 20.4% had nonalcoholic steatohepatitis, and 73.5% had
      fibrosis on index liver biopsy. Cirrhosis was diagnosed in 14 patients (24.6%)
      during follow-up. T1DM with age under 55 years had an odds ratio of 1.875 (95%
      confidence interval: 0.936-3.757) for cirrhosis incidence, compared to the
      general population. Longitudinal liver-related outcomes were similar comparing
      the T1DM cohort and respective type 2 diabetes cohorts--when adjusted for
      important confounders, diabetic cohort type did not predict altered risk of
      incident cirrhosis or portal hypertension. CONCLUSION: Type 1 diabetes is
      associated with a previously unrecognized burden of CLD and its complications.

PMID- 24585430
TI  - Fumonisin B1 induced neural tube defects were not increased in LM/Bc mice fed
      folate-deficient diet.
AB  - SCOPE: Fumonisin B1 (FB1 ) is found in corn-based foods and is a possible risk
      factor for neural tube defects (NTDs). The mechanism(s) underlying NTD induction
      by FB1 in LM/Bc mice is not understood; however, evidence suggests disrupted
      folate transport is involved. METHODS AND RESULTS: Female LM/Bc mice were fed
      folate-sufficient (control) or folate-deficient diet beginning 5 wk before
      mating, treated with 0 (vehicle), 2.5 or 10 mg/kg FB1 by intraperitoneal
      injection on embryonic days 7 (E7) and E8, and their fetuses examined on E16.
      Dose-dependent NTD induction was found in groups fed the control diet: 3 of 13
      low-dose and 10 of 11 high-dose litters were affected. Among groups fed folate
      deficient diet, NTDs were found only in 4 of 11 high-dose litters. In another
      trial, consumption of folate-deficient diet also resulted in fewer NTDs at a dose
      of 10 mg/kg FB1 and reduced maternal red blood cell folate levels by 80%. In
      utero death did not fully account for the differences in NTD rates. CONCLUSION:
      Folate deficiency does not exacerbate NTD induction by FB1 in LM/Bc mice.
      Interactions between folate, other nutritional factors, and FB1 in this mouse
      model for NTDs are complex and require further investigation.

PMID- 24585432
TI  - Randomized two-way cross-over bioequivalence study of two amoxicillin
      formulations and inter-ethnicity pharmacokinetic variation in healthy Malay
      volunteers.
AB  - The objectives of this study were to develop a new deproteinization method to
      extract amoxicillin from human plasma and evaluate the inter-ethnic variation of
      amoxicillin pharmacokinetics in healthy Malay volunteers. A single-dose,
      randomized, fasting, two-period, two-treatment, two-sequence crossover, open
      label bioequivalence study was conducted in 18 healthy Malay adult male
      volunteers, with one week washout period. The drug concentration in the sample
      was analyzed using high-performance liquid chromatography (UV-vis HPLC). The mean
      (standard deviation) pharmacokinetic parameter results of Moxilen(r) were: peak
      concentration (Cmax ), 6.72 (1.56) ug/mL; area under the concentration-time graph
      (AUC0-8 ), 17.79 (4.29) ug/mL h; AUC0-infinity , 18.84 (4.62) ug/mL h. Those of
      YSP Amoxicillin(r) capsule were: Cmax , 6.69 (1.44) ug/mL; AUC0-8 , 18.69 (3.78)
      ug/mL h; AUC00-infinity , 19.95 (3.81) ug/mL h. The 90% confidence intervals for
      the logarithmic transformed Cmax , AUC0-8 and AUC0-infinity of Moxilen(r) vs YSP
      Amoxicillin(r) capsule was between 0.80 and 1.25. Both Cmax and AUC met the
      predetermined criteria for assuming bioequivalence. Both formulations were well
      tolerated. The results showed significant inter-ethnicity variation in
      pharmacokinetics of amoxicillin. The Cmax and AUC of amoxicillin in Malay
      population were slightly lower compared with other populations.

PMID- 24585433
TI  - Efficiency of weak brain connections support general cognitive functioning.
AB  - Brain network topology provides valuable information on healthy and pathological
      brain functioning. Novel approaches for brain network analysis have shown an
      association between topological properties and cognitive functioning. Under the
      assumption that "stronger is better", the exploration of brain properties has
      generally focused on the connectivity patterns of the most strongly correlated
      regions, whereas the role of weaker brain connections has remained obscure for
      years. Here, we assessed whether the different strength of connections between
      brain regions may explain individual differences in intelligence. We analyzed
      functional connectivity at rest in ninety-eight healthy individuals of different
      age, and correlated several connectivity measures with full scale, verbal, and
      performance Intelligent Quotients (IQs). Our results showed that the variance in
      IQ levels was mostly explained by the distributed communication efficiency of
      brain networks built using moderately weak, long-distance connections, with only
      a smaller contribution of stronger connections. The variability in individual IQs
      was associated with the global efficiency of a pool of regions in the prefrontal
      lobes, hippocampus, temporal pole, and postcentral gyrus. These findings
      challenge the traditional view of a prominent role of strong functional brain
      connections in brain topology, and highlight the importance of both strong and
      weak connections in determining the functional architecture responsible for human
      intelligence variability.

PMID- 24585434
TI  - Serum ANGPTL2 levels reflect clinical features of breast cancer patients:
      implications for the pathogenesis of breast cancer metastasis.
AB  - INTRODUCTION: Breast cancer is a leading cause of cancer-related death in women
      worldwide, and its metastasis is a major cause of disease mortality. Therefore,
      identification of the mechanisms underlying breast cancer metastasis is crucial
      for the development of therapeutic and diagnostic strategies. Our recent study of
      immunodeficient female mice transplanted with MDA-MB231 breast cancer cells
      demonstrated that tumor cell-derived angiopoietin-like protein 2 (ANGPTL2)
      accelerates metastasis through both increasing tumor cell migration in an
      autocrine/paracrine manner, and enhancing tumor angiogenesis. To determine
      whether ANGPTL2 contributes to its clinical pathogenesis, we asked whether serum
      ANGPTL2 levels reflect the clinical features of breast cancer progression.
      METHODS: We monitored the levels of secreted ANGPTL2 in supernatants of cultured
      proliferating MDA-MB231 cells. We also determined whether the circulating ANGPTL2
      levels were positively correlated with cancer progression in an in vivo breast
      cancer xenograft model using MDA-MB231 cells. Finally, we investigated whether
      serum ANGPTL2 levels were associated with clinical features in breast cancer
      patients. RESULTS: Both in vitro and in vivo experiments showed that the levels
      of ANGPTL2 secreted from breast cancer cells increased with cell proliferation
      and cancer progression. Serum ANGPTL2 levels in patients with metastatic breast
      cancer were significantly higher than those in healthy subjects or in patients
      with ductal carcinoma in situ or non-metastatic invasive ductal carcinoma. Serum
      ANGPTL2 levels in patients negative for estrogen receptors and progesterone
      receptors, particularly triple-negative cases, reflected histological grades.
      CONCLUSIONS: These findings suggest that serum ANGPTL2 levels in breast cancer
      patients could represent a potential marker of breast cancer metastasis.

PMID- 24585435
TI  - Resistin -420C>G promoter variant and colorectal cancer risk.
AB  - PURPOSES: Obesity is associated with an increased risk of colorectal cancer
      (CRC), and ghrelin (GHRL) and resistin (RETN) are thought to be related to
      obesity. Our aim was to investigate whether GHRL and RETN gene variants are
      associated with CRC risk. MATERIALS AND METHODS: All 414 subjects, including 197
      cases with CRC and 217 controls, were genotyped for the GHRL (rs26802) and RETN
      (rs1862513) or -420 C>G gene variants using the PCR-RFLP method. RESULTS: Our
      findings indicated that the RETN -420 C>G "CC" genotype, compared with the "GG"
      and "GC" genotypes, was a marker of decreased CRC susceptibility; the difference
      remained significant after adjustment for age, BMI, gender, smoking status, NSAID
      use, and family history of CRC (p=0.020; OR=0.52, 95% CI=0.30-0.90). Furthermore,
      after adjustment for confounding factors, the -420 C>G "CC" genotype, compared
      with the "GG" genotype, was associated with a decreased risk for CRC (p=0.044;
      OR=0.53, 95% CI=0.29-0.98). In addition, no significant difference was observed
      for the GHRL (rs26802) gene variant. CONCLUSIONS: To our knowledge, this is the
      first study suggesting that the RETN -420 C>G "CC" genotype is a marker of
      decreased CRC susceptibility. This observation is relevant from a scientific
      perspective and deserves further investigations.

PMID- 24585436
TI  - Microfluidics for the analysis of membrane proteins: how do we get there?
AB  - The development of fully automated and high-throughput systems for proteomics is
      now in demand because of the need to generate new protein-based disease
      biomarkers. Unfortunately, it is difficult to identify protein biomarkers that
      are low abundant when in the presence of highly abundant proteins, especially in
      complex biological samples such as serum, cell lysates, and other biological
      fluids. Membrane proteins, which are in many cases of low abundance compared to
      the cytosolic proteins, have various functions and can provide insight into the
      state of a disease and serve as targets for new drugs making them attractive
      biomarker candidates. Traditionally, proteins are identified through the use of
      gel electrophoretic techniques, which are not always suitable for particular
      protein samples such as membrane proteins. Microfluidics offers the potential as
      a fully automated platform for the efficient and high-throughput analysis of
      complex samples, such as membrane proteins, and do so with performance metrics
      that exceed their bench-top counterparts. In recent years, there have been
      various improvements to microfluidics and their use for proteomic analysis as
      reported in the literature. Consequently, this review presents an overview of the
      traditional proteomic-processing pipelines for membrane proteins and insights
      into new technological developments with a focus on the applicability of
      microfluidics for the analysis of membrane proteins. Sample preparation
      techniques will be discussed in detail and novel interfacing strategies as it
      relates to MS will be highlighted. Lastly, some general conclusions and future
      perspectives are presented. 

PMID- 24585437
TI  - Symmetry breakage in the frog Xenopus: role of Rab11 and the ventral-right
      blastomere.
AB  - Vertebrates display asymmetric arrangements of inner organs such as heart and
      stomach. The Nodal signaling cascade in the left lateral plate mesoderm in all
      cases directs asymmetric morphogenesis and placement during organogenesis.
      Mechanisms that lead up to left-asymmetric Nodal induction seem to differ between
      the vertebrates. Cilia produce a leftward extracellular fluid flow in zebrafish,
      medaka, mouse, rabbit, and Xenopus embryos during neurulation. In Xenopus,
      earlier asymmetric cues were described. Some, such as Rab11, apparently act in
      the zygote. Others were efficiently manipulated in ventral-right cells at the
      four-cell stage, a lineage presumably independent of the ciliated gastrocoel roof
      plate (GRP) during neurulation. Here, we show that one- and four-cell
      manipulations of Rab11 showed equal low efficiencies of left-right disturbances.
      We also reevaluated the lineage of the GRP. By tracing back future ciliated cells
      from the gastrula to the four-cell stage, we show that ventral cells contribute
      to ciliated sensory cells at the border of the GRP. Knockdown of the Nodal
      inhibitor Coco in the ventral right lineage resulted in embryos with ectopic
      right-sided Nodal and Pitx2c expression. Together, these experiments support a
      cilia-based mechanism of symmetry breakage in the frog Xenopus.

PMID- 24585438
TI  - Moderate chronic administration of Vineatrol-enriched red wines improves
      metabolic, oxidative, and inflammatory markers in hamsters fed a high-fat diet.
AB  - SCOPE: High-fat (HF) diets contribute to the development of cardiovascular
      diseases and the metabolic syndrome. This study was undertaken to investigate the
      beneficial effects of Vineatrol(r)-enriched red wines on blood lipids, oxidative
      stress and inflammation, and the role of some metabolic pathway regulatory
      proteins. METHODS AND RESULTS: Golden Syrian hamsters received an HF diet for 13
      wk, in the presence or absence of red wines supplemented with Vineatrol(r) (RWV)
      or not. The HF diet increased plasma cholesterol, triglycerides, glucose, and
      insulin, which were attenuated by RWV treatment. RWV protected against the HF
      induced increase in liver nicotinamide adenine dinucleotide phosphate (NADPH)
      oxidase activity and spared antioxidant enzyme activities. RWV did not reduce
      either liver steatosis or increased plasma leptin due to the HF diet, but greatly
      improved adiponectinemia. In the liver, RWV affected the inflammatory response by
      decreasing polymorphonuclear cell number and lowering TNF-alpha and IL-6 levels.
      Moreover, the increase in NF-kappaB activity in the HF group liver was prevented
      by RWV. Finally, RWV partially corrected low SIRT1 levels due to the HF diet but
      had no influence on SIRT3 or p-AMPK protein levels. CONCLUSION: Our studies
      suggest that RWV is capable of reversing the atherogenic process induced by an HF
      diet in hamster tissues.

PMID- 24585439
TI  - Pediatric extracorporeal shock wave lithotripsy: multi-institutional results.
AB  - AIM: To evaluate the efficacy, auxiliary procedures and complications of
      pediatric extracorporeal shock wave lithotripsy (ESWL) performed with
      electrohydraulic lithotripters. METHODS: Children with urolithiasis, aged between
      0 and 15, were retrospectively evaluated. ESWL was performed by using two
      different electrohydraulic lithotripters, Elmed Multimed Classic (Elmed Medical
      Systems, Ankara, Turkey) and E-1000 (EMD Medical Systems, Ankara, Turkey),
      between January 2008 and December 2012 in four different referral centers in
      Turkey. RESULTS: 85.5% of patients were stone-free at 3 months. Further ESWL
      treatment was needed in 33.7% of the cases (one session, n = 55; two sessions, n
      = 15; three sessions, n = 13). Steinstrasse occurred in 10 patients but 8 of them
      cleared completely during the follow-up period. Urinary tract infection was
      detected in 3 (3.9%), fever in 3 (3.9%) and a small subcapsular hematoma in one
      (1.3%) patient, respectively. When the stones were divided into two groups as
      those with diameters <10 mm and >=10 mm, it was found that the stone-free rate
      was associated with stone diameter, and that the smaller diameters had higher but
      statistically insignificant stone-free rates (P = 0.196). CONCLUSION: ESWL yields
      favorable results with low rates of complication and auxiliary procedures in
      selected pediatric patients.

PMID- 24585440
TI  - [Comparison in the follow-up of two patients with persistent elevated PSA and
      negative prostate biopsy].
AB  - PURPOSE: To compare two clinical cases on the follow-up of patients with benign
      prostatic hyperplasia at risck of progression, negative prostate biopsy and
      persistent elevated PSA levels. MATERIALS: After a first negative prostate biopsy
      for elevated PSA levels, Case A received dutasteride therapy for benign prostatic
      hyperplasia, whereas Case B continued his therapy without dutasteride. In both
      cases, other diagnostic procedures or other biopsies were decided on the basis of
      PSA level modifications. RESULTS: Case A showed a stabilization of PSA levels
      with a new nadir; the patient did not undergo new biopsies or other diagnostic
      procedures till the presence (24 months of follow-up) of a PSA elevation despite
      dutasteride therapy. A new biopsy, then, showed a prostate adenocarcinoma. Case B
      showed persistent and progressive PSA elevation; the patient underwent other
      diagnostic procedures and 2 new negative biopsies. Only after 26 months of follow
      up a further biopsy showed a prostate adenocarcinoma. CONCLUSIONS: 5-alpha
      reductase inhibitors can reduce the number of unnecessary prostate biopsies.

PMID- 24585441
TI  - Polysialic acid/neural cell adhesion molecule modulates the formation of ductular
      reactions in liver injury.
AB  - In severe liver injury, ductular reactions (DRs) containing bipotential hepatic
      progenitor cells (HPCs) branch from the portal tract. Neural cell adhesion
      molecule (NCAM) marks bile ducts and DRs, but not mature hepatocytes. NCAM
      mediates interactions between cells and surrounding matrix; however, its role in
      liver development and regeneration is undefined. Polysialic acid (polySia), a
      unique posttranslational modifier of NCAM, is produced by the enzymes, ST8SiaII
      and ST8SiaIV, and weakens NCAM interactions. The role of polySia with NCAM
      synthesizing enzymes ST8SiaII and ST8SiaIV were examined in HPCs in vivo using
      the choline-deficient ethionine-supplemented and 3,5-diethoxycarbonyl-1,4
      dihydrocollidine diet models of liver injury and regeneration, in vitro using
      models of proliferation, differentiation, and migration, and by use of mouse
      models with gene defects in the polysialyltransferases (St8sia 2+/-4+/-, and
      St8sia2-/-4-/-). We show that, during liver development, polySia is required for
      the correct formation of bile ducts because gene defects in both the
      polysialyltransferases (St8sia2+/-4+/- and St8sia2-/-4-/- mice) caused abnormal
      bile duct development. In normal liver, there is minimal polySia production and
      few ductular NCAM+ cells. Subsequent to injury, NCAM+ cells expand and polySia is
      produced by DRs/HPCs through ST8SiaIV. PolySia weakens cell-cell and cell-matrix
      interactions, facilitating HGF-induced migration. Differentiation of HPCs to
      hepatocytes in vitro results in both transcriptional down-regulation of polySia
      and cleavage of polySia-NCAM. Cleavage of polySia by endosialidase (endoN) during
      liver regeneration reduces migration of DRs into parenchyma. CONCLUSION: PolySia
      modification of NCAM+ ductules weakens cell-cell and cell-matrix interactions,
      allowing DRs/HPCs to migrate for normal development and regeneration. Modulation
      of polySia levels may provide a therapeutic option in liver regeneration.

PMID- 24585443
TI  - Investigation of glutamine and GABA levels in patients with idiopathic
      generalized epilepsy using MEGAPRESS.
AB  - PURPOSE: Idiopathic generalized epilepsies (IGE) comprise a group of clinical
      syndromes associated with spike wave discharges, putatively linked to alterations
      in neurotransmission. The purpose of this study was to investigate whether
      patients with IGE have altered glutamine and gamma-aminobutyric acid (GABA)
      levels indicative of altered excitatory and inhibitory neurotransmission in
      frontal regions. MATERIALS AND METHODS: Single-voxel MEGA-edited PRESS magnetic
      resonance imaging (MRI) spectra were acquired from a 30-mL voxel in the
      dorsolateral prefrontal cortex in 13 patients with IGE (8 female) and 16 controls
      (9 female) at 3T. Metabolite concentrations were derived using LCModel.
      Differences between groups were investigated using an unpaired t-test. RESULTS:
      Patients with IGE were found to have significantly higher glutamine than controls
      (P = 0.02). GABA levels were also elevated in patients with IGE (P = 0.03).
      CONCLUSION: Patients with IGE have increased frontal glutamine and GABA compared
      with controls. Since glutamine has been suggested to act as a surrogate for
      metabolically active glutamate, it may represent a marker for excitatory
      neurotransmission.

PMID- 24585444
TI  - Effects of single dose and regular intake of green tea (Camellia sinensis) on DNA
      damage, DNA repair, and heme oxygenase-1 expression in a randomized controlled
      human supplementation study.
AB  - Regular intake of green tea (Camellia sinensis) lowers DNA damage in humans, but
      molecular mechanisms of genoprotection are not clear. Protection could be via
      direct antioxidant effects of tea catechins, but, paradoxically, catechins have
      pro-oxidant activity in vitro, and it is hypothesized that mechanisms relate to
      redox-sensitive cytoprotective adaptations. We investigated this hypothesis,
      focusing particularly on effects on the DNA repair enzyme human oxoguanine
      glycosylase 1 (hOGG1), and heme oxygenase-1, a protein that has antioxidant and
      anti-inflammatory effects. A randomized, placebo-controlled, human
      supplementation study of crossover design was performed. Subjects (n = 16) took a
      single dose (200 mL of 1.5%, w/v) and 7-days of (2 * 200 mL 1%, w/v per day)
      green tea (with water as control treatment). Lymphocytic DNA damage was ~30% (p <
      0.001) lower at 60 and 120 min after the single dose and in fasting samples
      collected after 7-day tea supplementation. Lymphocytic hOGG1 activity was higher
      (p < 0.0001) at 60 and 120 min after tea ingestion. Significant increases (p <
      0.0005) were seen in hOGG1 activity and heme oxygenase-1 after 7 days. Results
      indicate that molecular triggering of redox-sensitive cytoprotective adaptations
      and posttranslational changes affecting hOGG1 occur in vivo in response to both a
      single dose and regular intake of green tea, and contribute to the observed
      genoprotective effects of green tea. 

PMID- 24585442
TI  - A proinvasive role for the Ca(2+) -activated K(+) channel KCa3.1 in malignant
      glioma.
AB  - Glioblastoma multiforme are highly motile primary brain tumors. Diffuse tissue
      invasion hampers surgical resection leading to poor patient prognosis. Recent
      studies suggest that intracellular Ca(2+) acts as a master regulator for cell
      motility and engages a number of downstream signals including Ca(2+) -activated
      ion channels. Querying the REepository of Molecular BRAin Neoplasia DaTa
      (REMBRANDT), an annotated patient gene database maintained by the National Cancer
      Institute, we identified the intermediate conductance Ca(2+) -activated K(+)
      channels, KCa3.1, being overexpressed in 32% of glioma patients where protein
      expression significantly correlated with poor patient survival. To
      mechanistically link KCa3.1 expression to glioma invasion, we selected patient
      gliomas that, when propagated as xenolines in vivo, present with either high or
      low KCa3.1 expression. In addition, we generated U251 glioma cells that stably
      express an inducible knockdown shRNA to experimentally eliminate KCa3.1
      expression. Subjecting these cells to a combination of in vitro and in situ
      invasion assays, we demonstrate that KCa3.1 expression significantly enhances
      glioma invasion and that either specific pharmacological inhibition with TRAM-34
      or elimination of the channel impairs invasion. Importantly, after intracranial
      implantation into SCID mice, ablation of KCa3.1 with inducible shRNA resulted in
      a significant reduction in tumor invasion into surrounding brain in vivo. These
      results show that KCa3.1 confers an invasive phenotype that significantly worsens
      a patient's outlook, and suggests that KCa3.1 represents a viable therapeutic
      target to reduce glioma invasion.

PMID- 24585445
TI  - Critical concentration of ion-pairs formation in nonpolar media.
AB  - It is known that nonpolar liquids can be ionized by adding surfactants, either
      ionic or nonionic. Surfactant molecules serve as solvating agents, building
      inverse micelles around ions, and preventing their association back into neutral
      molecules. According to the Bjerrum-Onsager-Fuoss theory, these inverse micelle
      ions should form "ion pairs." This, in turn, leads to nonlinear dependence of the
      conductivity on the concentration. Surprisingly, ionic surfactants exhibit linear
      conductivity dependence, which implies that these inverse micelle ions do not
      form ion pairs. Theory predicts the existence of two ionic strength ranges, which
      are separated by a certain critical ion concentration. Ionic strength above the
      critical one is proportional to the square root of the ion concentration, whereas
      it becomes linear below the critical concentration. Critical ion concentration
      lies within the range of 10(-11) -10(-7) mol/L when ion size ranges from 1 to 3
      nm. Critical ion concentration is related, but not equal, to a certain surfactant
      concentration (critical concentration of ion-pairs formation (CIPC)) because only
      a fraction of the surfactant molecules is incorporated into the micelles ions.
      The linear conductivity dependence for ionic surfactants indicates that the
      corresponding CIPC is above the range of studied concentrations, perhaps, due to
      rather large ion size. The same linearity is a sign that charged inverse micelles
      structure and fraction are concentration independent due to strong charge-dipole
      interaction in the charge micelle core. This also proves that CIPC is independent
      of critical concentration of micelle formation. Nonionic surfactants, on the
      other hand, exhibit nonlinear conductivity dependence apparently due to smaller
      ion sizes.

PMID- 24585446
TI  - Genetic variants in the SWI/SNF complex and smoking collaborate to modify the
      risk of pancreatic cancer in a Chinese population.
AB  - Pancreatic cancer (PC) is an aggressive malignancy with extremely low 5-year
      survival rate (<5%). SWItch/Sucrose Non Fermentable (SWI/SNF) complex is a core
      factor for chromatin-remodeling that utilize energy of ATP hydrolysis to mobilize
      nucleosomes, and modulate gene transcription. Recent studies have identified
      recurrent mutations in major components of SWI/SNF in a variety of human cancers,
      including PC. We conducted a two-stage case-control study to investigate the
      associations between 14 common variants in 6 genes (SMARCA4, SMCRB1, PBRM1, BRD7,
      ARID1, and ARID2) encoding major components of the SWI/SNF complex and the risk
      of PC. Three promising variants, rs11644043, rs11085754, and rs2073389 in the
      discovery stage comprising 310 cases and 457 controls were further genotyped in
      the validation stage containing 429 cases and 585 controls. rs11644043 in BRD7
      and rs11085754 in SMARCA4 showed consistent significant association with
      increased risk of PC in both stages, with odds ratios (ORs) and 95% confidence
      interval (CI) of 2.04 (1.17-3.56) and 1.64 (1.16-2.33) in stage one, and 1.97
      (1.24-3.14) and 1.45 (1.04-2.02) in stage two, respectively in a recessive model.
      Furthermore, the accumulative effects of rs11644043, rs11085754, and rs2073389 in
      SMARCB1 were observed (P for trend <0.0001). Intriguingly, gene-environmental
      interactions analysis consistently revealed the potential interactions of
      rs2073389 (P(add)  - FDR = 6.00 * 10(-4), P(mul)  - FDR = 1.50 * 10(-2)) and
      rs11085754 (P(add)  - FDR = 0.03) collaborating with smoking to modify the risk
      of PC. In conclusion, the current study provides evidence that genetic variants
      of SWI/SNF may contribute to the susceptibility of PC in the Chinese population.

PMID- 24585447
TI  - The Zic2 gene directs the formation and function of node cilia to control cardiac
      situs.
AB  - The first molecular herald of organ asymmetry during murine embryogenesis is
      found at the periphery of the node in early-somite stage embryos. Asymmetric gene
      expression and calcium accumulation at the node occurs in response to a left-ward
      flow of extracellular fluid across the node, generated by motile cilia within the
      pit of the node and likely sensed by immotile cilia in the periphery of the node.
      The ciliation of node cells is controlled by a cascade of node-restricted
      transcription factor activity during mid-late gastrulation. Mutation of the
      murine Zic2 transcription factor is associated with random cardiac situs and a
      loss of asymmetric gene expression at the early-somite node and in the lateral
      plate. Zic2 is not expressed in these regions but is transiently expressed in the
      mid-late gastrula node at the time of ciliogenesis. The cilia of the node are
      overtly abnormal in Zic2 mutant embryos being dysmorphic and short relative to
      wild-type littermates. The expression of the Noto, Rfx3, and Foxj1 transcription
      factors known to regulate ciliogenesis is greatly depleted in the mid-gastrula
      node of mutants, as is the expression of the Pkd1l1 gene required for cilia
      function. Zic2 appears to be a component of the gene regulatory network that
      drives ciliation of node cells during gastrulation.

PMID- 24585448
TI  - Reply: To PMID 24442928.

PMID- 24585449
TI  - Effect of cell density on mesenchymal stem cells aggregation in RGD-alginate 3D
      matrices under osteoinductive conditions.
AB  - Cellular activities in 3D are differentially affected by several matrix-intrinsic
      and extrinsic factors. This study highlights the relevance of optimizing initial
      cell densities when establishing 3D cultures for specific applications.
      Independently of the entrapping density, MSCs cultured within RGD-alginate
      hydrogels showed steady-state levels of metabolic activity and were in a nearly
      non-proliferative state, but recovered "normal" activity levels when retrieved
      from 3D matrices and re-cultured as monolayers. Importantly, high-densities
      promoted the establishment of cell-cell contacts with formation of multicellular
      clusters stabilized by endogenous ECM, and also stimulated MSCs osteogenic
      differentiation. These MSC-ECM microtissues may be used as building blocks for
      tissue engineering. 

PMID- 24585450
TI  - Postmortem microcomputed tomography (micro-CT) of small fetuses and hearts.
AB  - OBJECTIVE: To assess the feasibility and utility of contrast-enhanced
      microcomputed tomography (micro-CT) for identifying structural anomalies in ex
      vivo first- and second-trimester human fetuses and isolated fetal hearts.
      METHODS: Radiopaque iodine staining and micro-CT scanning protocols were first
      developed in rodent studies and then used to examine routinely fixed whole human
      fetuses (n = 7, weight 0.1-90 g, gestational age, 7-17 weeks) and isolated fetal
      hearts (n = 14, weight 0.1-5.2 g, gestational age, 11-22 weeks). Samples were
      scanned using an isotropic resolution of 18 (and, if necessary, 9 or 35) um and
      findings were interpreted jointly by four fetal pathologists, a fetal
      cardiologist and a radiologist. Samples with gestational ages >= 13 weeks also
      underwent conventional autopsy or dissection. RESULTS: Micro-CT identified all
      anatomical structures and abnormalities documented by the macroscopic
      examination. In all seven cases involving fetuses <= 13 weeks (four fetuses,
      three isolated hearts), micro-CT excluded the presence of structural anomalies.
      In the remaining 14 cases, it provided all the information obtained with invasive
      autopsy or dissection and in seven of the 14 (two fetuses, five isolated hearts)
      it furnished additional diagnostic details. CONCLUSIONS: This pilot study
      confirms the feasibility of postmortem contrast-enhanced micro-CT assessment of
      structural anomalies in whole small fetuses and fetal hearts. Further study is
      needed to confirm our findings, particularly in whole fetuses, and to define the
      extent to which this virtual examination might be used instead of conventional
      invasive autopsy.

PMID- 24585451
TI  - Peginterferon alpha-2a versus peginterferon alpha-2b for chronic hepatitis C.
AB  - BACKGROUND: A combination of weekly pegylated interferon (peginterferon) alpha
      and daily ribavirin still represents standard treatment of chronic hepatitis C
      infection in the majority of patients. However, it is not established which of
      the two licensed peginterferon products, peginterferon alpha-2a or peginterferon
      alpha-2b, is the most effective and has a better safety profile. OBJECTIVES: To
      systematically evaluate the benefits and harms of peginterferon alpha-2a versus
      peginterferon alpha-2b in head-to-head randomised clinical trials in patients
      with chronic hepatitis C. SEARCH METHODS: We searched the Cochrane Hepato-Biliary
      Group Controlled Trials Register, the Cochrane Central Register of Controlled
      Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, Science Citation Index
      Expanded, and LILACS until October 2013. We also searched conference abstracts,
      journals, and grey literature. SELECTION CRITERIA: We included randomised
      clinical trials comparing peginterferon alpha-2a versus peginterferon alpha-2b
      given with or without co-intervention(s) (for example, ribavirin) for chronic
      hepatitis C. Quasi-randomised studies and observational studies as identified by
      the searches were also considered for assessment of harms. Our primary outcomes
      were all-cause mortality, liver-related morbidity, serious adverse events,
      adverse events leading to treatment discontinuation, other adverse events, and
      quality of life. The secondary outcome was sustained virological response in the
      blood serum. DATA COLLECTION AND ANALYSIS: Two authors independently used a
      standardised data collection form. We meta-analysed data with both the fixed
      effect and the random-effects models. For each outcome we calculated the relative
      risk (RR) with 95% confidence interval (CI) based on intention-to-treat analysis.
      We used domains of the trials to assess the risk of systematic errors (bias) and
      trial sequential analyses to assess the risks of random errors (play of chance).
      Intervention effects on the outcomes were assessed according to GRADE. MAIN
      RESULTS: We included 17 randomised clinical trials which compared peginterferon
      alpha-2a plus ribavirin versus peginterferon alpha-2b plus ribavirin in 5847
      patients. All trials had a high risk of bias. Very few trials reported data on
      very few patients for the patient-relevant outcomes all-cause mortality, liver
      related morbidity, serious adverse events, and quality of life. Accordingly, we
      were unable to conduct meta-analyses on all-cause mortality, liver-related
      morbidity, and quality of life. Twelve trials reported on adverse events leading
      to discontinuation of treatment without clear evidence of a difference between
      the two peginterferons (197/2171 (9.1%) versus 311/3169 (9.9%); RR 0.84, 95% CI
      0.57 to 1.22; I2 = 44%; low quality evidence). A trial sequential analysis showed
      that we could exclude a relative risk reduction of 20% or more on this outcome.
      Peginterferon alpha-2a significantly increased the number of patients who
      achieved a sustained virological response in the blood serum compared with
      peginterferon alpha-2b (1069/2099 (51%) versus 1327/3075 (43%); RR 1.12, 95% CI
      1.06 to 1.18; I2= 0%, 12 trials; moderate quality evidence). Trial sequential
      analyses supported this result. Subgroup analyses based on risk of bias, viral
      genotype, and treatment history yielded similar results. Trial sequential
      analyses supported the results in patients with genotypes 1 and 4, but not in
      patients with genotypes 2 and 3. AUTHORS' CONCLUSIONS: There is lack of evidence
      on patient-important outcomes and paucity of evidence on adverse events. Moderate
      quality evidence suggests that peginterferon alpha-2a is associated with a higher
      sustained virological response in serum than with peginterferon alpha-2b. This
      finding may be affected by the high risk of bias of the included studies . The
      clinical consequences of peginterferon alpha-2a versus peginterferon alpha-2b are
      unknown, and we cannot translate an effect on sustained virological response into
      comparable clinical effects because sustained virological response is still an
      unvalidated surrogate outcome for patient-important outcomes. The lack of
      evidence on patient-important outcomes and the paucity of evidence on adverse
      events means that we are unable to draw any conclusions about the effects of one
      peginterferon over the other.

PMID- 24585452
TI  - Detection of glutamate, glutamine, and glutathione by radiofrequency suppression
      and echo time optimization at 7 tesla.
AB  - PURPOSE: To achieve detection of glutamate (Glu), glutamine (Gln), and
      glutathione (GSH) by minimizing the N-acetyl-aspartate (NAA) multiplet signals at
      2.49 ppm using a echo time (TE) -optimized PRESS pulse sequence and a novel J
      suppression radiofrequency pulse. METHODS: Using density matrix simulations, a
      PRESS sequence with (TE1 , TE2 ) = (69, 37) ms and an inserted 90 degrees  J
      suppression pulse were found to minimize the NAA multiplet at 2.49 ppm. RESULTS:
      NAA phantom experiments confirmed the successful suppression of the NAA multiplet
      at 2.49 ppm. A study of eight healthy volunteers found both Glu and Gln to be
      significantly higher in gray matter (GM) dominant medial prefrontal cortex voxels
      than in white matter (WM) dominant right frontal cortex voxels. Time-course (1) H
      spectra acquired during intravenous [U-(13) C6 ]glucose infusion showed gradually
      changing Glu C4 and Gln C4 proton resonance signals in a spectral pattern
      predicted by numerical simulations. CONCLUSION: Reliable detection of Glu, Gln,
      and GSH was achieved. Glu and Gln levels were significantly higher in frontal
      lobe GM than in frontal lobe WM. It is feasible to use the proposed proton MR
      spectroscopy method to measure the kinetics of (13) C incorporation into Glu and
      Gln during infusion of (13) C labeled glucose.

PMID- 24585453
TI  - Reply: To PMID 24123276.

PMID- 24585454
TI  - Oxidative metabolism enhances the cytotoxic and genotoxic properties of the soy
      isoflavone daidzein.
AB  - SCOPE: Oxidative metabolism of daidzein (DAI) might result in the formation of
      hydroxylated metabolites. Here, we address the question whether these metabolites
      differ in their biological activity from the parent isoflavone, exemplified for
      the epidermal growth factor receptor and topoisomerase II, potentially resulting
      in an enhanced toxic profile. METHODS AND RESULTS: In contrast to DAI, 6
      hydroxydaidzein (6-HO-DAI) and 8-hydroxydaidzein (8-HO-DAI) were found to inhibit
      the tyrosine kinase activity of the epidermal growth factor receptor in an ELISA
      based test system, but showed no effects within cells. Further, the oxidative
      metabolites suppressed the catalytic activity of topoisomerase II in the
      decatenation assay. In the in vivo complexes of enzyme to DNA (ICE) bioassay, 6
      HO-DAI and 8-HO-DAI did not affect the level of covalent topoisomerase II-DNA
      intermediates within HT29 cells, thus arguing for a catalytic inhibition of
      topoisomerase II rather than poisoning activity. In contrast to DAI, 6-HO-DAI and
      8-HO-DAI significantly increased the rate of DNA strand breaks in HT29 cells
      after 24-h incubation and caused a cell cycle delay in S-phase. Differences were
      also observed between the oxidative metabolites, with only 6-HO-DAI inducing
      apoptosis but not 8-HO-DAI. CONCLUSION: These data indicate that oxidative
      metabolism of DAI generates metabolites with genotoxic properties where
      interference with topoisomerase II might play a role.

PMID- 24585455
TI  - Rim sign in breast lesions on diffusion-weighted magnetic resonance imaging:
      diagnostic accuracy and clinical usefulness.
AB  - PURPOSE: To investigate the diagnostic accuracy and clinical usefulness of the
      rim sign in breast lesions observed in diffusion-weighted magnetic resonance
      imaging (DWI). MATERIALS AND METHODS: The magnetic resonance imaging (MRI)
      findings of 98 pathologically confirmed lesions (62 malignant and 36 benign) in
      84 patients were included. Five breast radiologists were asked to independently
      review the breast MRI results, to grade the degree of high peripheral signal, the
      "rim sign," in the DWI, and to confirm the mean apparent diffusion coefficient
      (ADCmean ) values. We analyzed the diagnostic accuracy and compared the consensus
      (when >= 4 of 5 independent reviewers agreed) results of the rim sign with the
      ADCmean values. Additionally, we evaluated the correlation between the dynamic
      contrast-enhanced (DCE)-MRI morphologic appearance and DWI rim sign. RESULTS:
      According to the consensus results, the rim sign in DWI was observed on 59.7% of
      malignant lesions and 19.4% of benign lesions. The sensitivity, specificity, and
      area under the curve (AUC) value for the rim sign in DWI were 59.7%, 80.6%, and
      0.701, respectively. The sensitivity, specificity, and AUC value for the ADCmean
      value (criteria <= 1.46 * 10(-3) mm(2) /sec) were 82.3%, 63.9%, and 0.731,
      respectively. Based on consensus, no correlation was observed between the DCE-MRI
      and DWI rim signs. CONCLUSION: In DWI, a high-signal rim is a valuable
      morphological feature for improving specificity in DWI.

PMID- 24585456
TI  - Re-analysis of the PREGNANT trial confirms that vaginal progesterone reduces the
      rate of preterm birth in women with a sonographic short cervix.

PMID- 24585457
TI  - Post-treatment recovery of suboptimal DNA repair capacity and gene expression
      levels in colorectal cancer patients.
AB  - DNA repair in blood cells was observed to be suboptimal in cancer patients at
      diagnosis, including colorectal cancer (CRC). To explore the causality of this
      phenomenon, we studied the dynamics of DNA repair from diagnosis to 1 yr follow
      up, and with respect to CRC treatment. Systemic CRC therapy is targeted to DNA
      damage induction and DNA repair is thus of interest. CRC patients were blood
      sampled three times in 6-mo intervals, starting at the diagnosis, and compared to
      healthy controls. DNA repair was characterized by mRNA levels of 40 repair genes,
      by capacity of nucleotide excision repair (NER), and by levels of DNA strand
      breaks (SBs). NER and base excision repair genes were significantly under
      expressed (P < 0.016) in patients at diagnosis compared to controls, in
      accordance with reduced NER function (P = 0.008) and increased SBs (P = 0.015).
      Six months later, there was an increase of NER capacity, but not of gene
      expression levels, in treated patients only. A year from diagnosis, gene
      expression profiles and NER capacity were significantly modified in all patients
      and were no longer different from those measured in controls. All patients were
      free of relapse at the last sampling, so we were unable to clarify the impact of
      DNA repair parameters on treatment response. However, we identified a panel of
      blood DNA repair-related markers discerning acute stage of the disease from the
      remission period. In conclusion, our results support a model in which DNA repair
      is altered as a result of cancer.

PMID- 24585458
TI  - Content and molecular weight of water-extractable arabinoxylans in wheat malt and
      wheat malt-based wort with different Kolbach indices.
AB  - BACKGROUND: Arabinoxylans (AXs) are partially water-extractable polymers that
      cause problems of viscosity and filterability during beer brewing. This study
      investigated the effects of Kolbach index (KI) on water-extractable AXs (WEAXs).
      RESULTS: KI had positive correlations with extract (r = 0.845) and free amino
      nitrogen (FAN) (r = 0.958). The contents of malt WEAXs (WEAXsm), total AXs and
      wort AXs (WAXs) were 10.8-11.6 g kg-1, 57.5-60.8 g kg-1 and 137.5-140.5 mg per
      100 mL respectively and the corresponding arabinose/xylose (A/X) ratios were 0.52
      0.56, 0.55-0.62 and 0.48-0.50. The molecular weight (Mw) ranged from 4.92 * 104
      to 6.93 * 104 Da for WEAXsm and from 1.24 * 104 to 2.90 * 104 Da for WAXs. KI had
      negative correlations with the average degree of polymerization (avDP) of malt (r
      = -0.877) and wort (r = -0.978). Wort viscosity showed a positive correlation
      with the Mw of WEAXsm (Mwm) (r = 0.821). CONCLUSION: Increasing KI can promote
      the degradation of the xylan backbone, while it cannot affect the branching of
      the polymer chain and the content and Mw of WEAXs.

PMID- 24585459
TI  - VEGF-C mediates RhoGDI2-induced gastric cancer cell metastasis and cisplatin
      resistance.
AB  - Rho GDP dissociation inhibitor 2 (RhoGDI2) expression is correlated with tumor
      growth, metastasis and chemoresistance in gastric cancer. However, the mechanisms
      by which RhoGDI2 promotes tumor cell survival and metastasis remain unclear. In
      this study, we clearly demonstrate that RhoGDI2 upregulates VEGF-C expression and
      RhoGDI2 expression is positively correlated with VEGF-C expression in human
      gastric tumor tissues as well as parental gastric cancer cell lines. VEGF-C
      depletion suppressed RhoGDI2-induced gastric cancer metastasis and sensitized
      RhoGDI2-overexpressing cells to cisplatin-induced apoptosis in vitro and in vivo.
      Secreted VEGF-C enhanced gastric cancer cell invasion and conferred cisplatin
      resistance to RhoGDI2-overexpressing cells. We also show that RhoGDI2 positively
      regulates Rac1 activity in gastric cancer cells. Inhibition of Rac1 expression
      suppressed RhoGDI2-induced VEGF-C expression, and this inhibition was associated
      with decreased invasiveness and increased sensitivity to cisplatin in RhoGDI2
      overexpressing cells. Our results indicate that RhoGDI2 might be a potential
      therapeutic target for simultaneously reducing metastasis risk and enhancing
      chemotherapy efficacy in gastric cancer. 

PMID- 24585460
TI  - Separation of alogliptin enantiomers in cyclodextrin-modified capillary
      electrophoresis: a validated method.
AB  - The single enantiomer drug, alogliptin (Alo, Nesina(r)) is a novel, orally
      available and selective dipeptidyl peptidase-4 inhibitor used for the treatment
      of type II diabetes. Following its pKa determination by CE-pH titration, a
      validated chiral CE method has been developed to separate Alo enantiomers.
      Preliminary screening of the native CDs and their ten derivatives revealed that
      sulfopropylated-gamma-CD, sulfopropylated-beta-CD and sulfopropylated-gamma-CD,
      sulfobutyl-ether-beta-CD (SBE-beta-CD) and sulfobutyl-ether-gamma-CD enabled
      enantioresolution. Furthermore, cavity size dependent enantiomer migration order
      reversal was observed between gamma- and beta-CD derivatives. To improve
      enantioseparation, buffer composition and pH, CD concentration, applied voltage,
      temperature, and injection parameters were optimized for the Alo/ SBE-beta-CD
      system, yielding a resolution of 8.34. RSD percentage of the resolution value,
      migration times, and corrected peak areas were below 3 and 5% during testing
      repeatability and intermediate precision. LOD and LOQ values were found to be 2
      and 6 MUg/mL, respectively, for each enantiomer. Calibration lines ranging from 6
      to 250 MUg/mL were constructed with r(2) > 0.9997. Robustness could be
      successfully verified by using the Plackett-Burman statistical experimental
      design. The optimized system containing 5 mM SBE-beta-CD in a 25 mM acetate
      buffer at pH 4.75 was found promising to detect 0.1% distomer in the presence of
      the API. 

PMID- 24585462
TI  - Advances: the next stage of the journey.

PMID- 24585461
TI  - Glycyrrhizic acid attenuated glycative stress in kidney of diabetic mice through
      enhancing glyoxalase pathway.
AB  - SCOPE: Antiglycative effects of glycyrrhizic acid (GA) in kidney of diabetic mice
      were examined. METHODS AND RESULTS: GA at 0.05, 0.1, and 0.2% was supplied to
      diabetic mice for 9 wk. Results showed that GA intake increased its deposit in
      kidney, raised plasma insulin level, decreased plasma glucose and blood urine
      nitrogen levels, and improved creatinine clearance rate (p < 0.05). GA intake
      dose-dependently reduced renal carboxymethyllysine level, and at 0.1 and 0.2%
      decreased plasma HbA1c, urinary glycated albumin, and renal pentosidine levels (p
      < 0.05). Dietary GA intake declined renal aldose reductase activity and protein
      expression, as well as lowered renal fructose and sorbitol levels (p < 0.05). GA
      intake dose-dependently increased glyoxalase-1 activity and expression, and
      decreased renal methylglyoxal level (p < 0.05). This compound at 0.1 and 0.2%
      raised glyoxalase-2 activity and protein expression, and increased d-lactate
      formation (p < 0.05). GA intake dose-dependently suppressed renal expression of
      nuclear factor kappa B (NF-kappaB) p65 and p-p38, decreased reactive oxygen
      species production, and retained glutathione content (p < 0.05). This compound at
      0.1 and 0.2% downregulated renal expression of NF-kappaB p50 and p-ERK1/2 (p <
      0.05), and lowered renal level of monocyte chemoattractant protein-1 (MCP-1) and
      intercellular adhesion molecule-1 (ICAM-1). CONCLUSIONS: These findings suggest
      that glycyrrhizic acid is an antiglycative and renal-protective agent.

PMID- 24585463
TI  - The University of California Institute of Environmental Stress marathon field
      studies.
AB  - In 1973, the Institute of Environmental Stress of the University of California
      Santa Barbara, under the direction of Steven M. Horvath, began a series of field
      and laboratory studies of marathon runners during competition. As one of
      Horvath's graduate students, many of these studies became part of my doctoral
      dissertation. The rationale for studying runners under race conditions was based
      on my belief as a marathoner that runners would push themselves much harder while
      competing than under simulated conditions in the laboratory. Horvath's ready
      support of the studies likely had its roots in his graduate training at the
      Harvard Fatigue Laboratory, a laboratory well known for its field studies of
      individuals working in extreme environments. This report describes the studies of
      1973-1975, focusing on how the measurements were made and detailing the learning
      experiences of a new graduate student. In 1973, blood chemistry and fluid shifts
      were studied in six runners before and for 3 days after a race. This was the
      first modern study to systematically examine the recovery process. In 1974,
      oxygen consumption was measured every 3 mi. in two runners during the race. In
      1975, rectal temperature and five skin temperatures were evaluated in the same
      two runners every 1.4 mi. of the race. The latter two studies were the first to
      make such measurements under race conditions. The Institute of Environmental
      Stress marathon studies demonstrated the possibility of making measurements
      during competition without disrupting performance, enhanced our understanding of
      human exercise capacity under competitive conditions, and provided new insight
      into the postrace recovery process. 

PMID- 24585464
TI  - Using a classic paper by Bell as a platform for discussing the role of corollary
      discharge-like signals in sensory perception and movement control.
AB  - Decades of behavioral observations have shown that invertebrate and vertebrate
      species have the ability to distinguish between self-generated afferent inputs
      versus those that are generated externally. In the present article, I describe
      activities focused around the discussion of a classic American Physiological
      Society paper by Curtis C. Bell that lays the foundation for students to
      investigate the neural substrate underlying this ability. Students will leave
      this activity being able to 1) describe the technical aspects and limitations of
      an electric fish preparation commonly used to acquire single unit (extracellular)
      neurophysiological data, 2) provide physiological evidence showing that the
      activity of principal cells in the posterior lateral line lobe of the electric
      fish brain reflects that of a reafference comparator that could be used in
      dissociating self-generated versus externally generated sensory signals, and 3)
      knowledgeably discuss hypotheses concerning the role of corollary discharge and
      cerebellar-like structures in vertebrate and invertebrate species. The skills and
      background knowledge gained in this activity lay the platform for advanced study
      of scientific investigations into sensory, motor, and cognitive processes in
      undergraduate, graduate, or medical school curricula. 

PMID- 24585466
TI  - Exploratory study of factors related to educational scores of first preclinical
      year medical students.
AB  - The relationships among the scores of major subjects taught in the first
      preclinical year of a Thai medical school, previous academic achievements, and
      daily life activities are rarely explored. We therefore performed an exploratory
      study identifying various factors possibly related to the educational scores of
      these medical students. Questionnaires were sent out to all first preclinical
      year medical students, with 79.8% being returned (245/307 questionnaires).
      Positive correlations were revealed between the premedical year grade point
      average (pre-MD GPA) and anatomy, physiology, and biochemistry scores (R = 0.664,
      0.521, and 0.653, respectively, P < 0.001 for all) by Pearson's method. Using
      multiple linear regression analysis, anatomy scores could be predicted by pre-MD
      GPA, student satisfaction with anatomy, the percentage of expected reading,
      monthly earnings, reading after class and near exam time, and duration of
      sleeping periods near exam time (R = 0.773, R(2) = 0.598, P < 0.001). Physiology
      scores could be estimated by pre-MD GPA, the percentage of expected reading,
      monthly earnings, and percentage of those who fell asleep during class and near
      exam time (R = 0.722, R(2) = 0.521, P < 0.001). Biochemistry scores could be
      calculated by pre-MD GPA, the percentage of expected reading, motivation to study
      medicine, student satisfaction with biochemistry, and exam performance
      expectations (R = 0.794, R(2) = 0.630, P < 0.001). In conclusion, pre-MD GPA and
      the percentage of expected reading are factors involved in producing good
      academic results in the first preclinical year. Anatomy and biochemistry, but not
      physiology, scores are influenced by satisfaction. 

PMID- 24585467
TI  - Interactive computer-assisted instruction in acid-base physiology for mobile
      computer platforms.
AB  - In this project, the traditional lecture hall presentation of acid-base
      physiology in the first-year medical school curriculum was replaced by
      interactive, computer-assisted instruction designed primarily for the iPad and
      other mobile computer platforms. Three learning modules were developed, each with
      ~20 screens of information, on the subjects of the CO2-bicarbonate buffer system,
      other body buffer systems, and acid-base disorders. Five clinical case modules
      were also developed. For the learning modules, the interactive, active learning
      activities were primarily step-by-step learner control of explanations of complex
      physiological concepts, usually presented graphically. For the clinical cases,
      the active learning activities were primarily question-and-answer exercises that
      related clinical findings to the relevant basic science concepts. The student
      response was remarkably positive, with the interactive, active learning aspect of
      the instruction cited as the most important feature. Also, students cited the
      self-paced instruction, extensive use of interactive graphics, and side-by-side
      presentation of text and graphics as positive features. Most students reported
      that it took less time to study the subject matter with this online instruction
      compared with subject matter presented in the lecture hall. However, the approach
      to learning was highly examination driven, with most students delaying the study
      of the subject matter until a few days before the scheduled examination. Wider
      implementation of active learning computer-assisted instruction will require that
      instructors present subject matter interactively, that students fully embrace the
      responsibilities of independent learning, and that institutional administrations
      measure instructional effort by criteria other than scheduled hours of
      instruction. 

PMID- 24585468
TI  - Evaluation of retention of knowledge and skills imparted to first-year medical
      students through basic life support training.
AB  - Poor awareness among medical graduates about basic life support (BLS) is a matter
      of great concern. The presence of a trained rescuer is the key determinant of
      ultimate survival from life-threatening emergencies. To achieve this goal, early
      exposure to such life-saving skills is the right decision to foster these skills
      for medical students, which can be reenforced in succeeding years. Forty-two
      first-year medical students participated in this study. The entire procedure
      consisted of faculty training, assessment of knowledge of students by a pretest
      questionnaire, a lecture, a demonstration, and hands-on training using a
      mannequin (with special emphasis on the site, depth, rate, and sustainment of
      uninterrupted chest compressions). Posttest 1 was conducted to assess the
      knowledge gained. The retention of knowledge and skills in the second year was
      evaluated by posttest 2 and directly observed procedural skills, respectively.
      Student feedback was collected on five-point Likert scale. Analysis using a
      Freidman test indicated the mean rank for posttest 1 (2.81) to be significantly
      higher than the pretest (1.26), indicating a gain in knowledge. The mean rank for
      posttest 2 (1.93) was lower than for posttest 1 (2.81) but was significantly
      higher compared with the pretest (1.26), indicating a significant retention of
      knowledge during the second year. Directly observed procedural skill evaluation
      showed that 7% students could perform all the seven steps correctly and that 74%
      students could perform three or more steps correctly, signifying a good retention
      of skill. Two students taught BLS skills to their family members as well. The
      results of this study suggest that the program provides students with sound basic
      knowledge and adequate practical skills in BLS. 

PMID- 24585465
TI  - The immune system in hypertension.
AB  - While hypertension has predominantly been attributed to perturbations of the
      vasculature, kidney, and central nervous system, research for almost 50 yr has
      shown that the immune system also contributes to this disease. Inflammatory cells
      accumulate in the kidneys and vasculature of humans and experimental animals with
      hypertension and likely contribute to end-organ damage. We and others have shown
      that mice lacking adaptive immune cells, including recombinase-activating gene
      deficient mice and rats and mice with severe combined immunodeficiency have
      blunted hypertension to stimuli such as ANG II, high salt, and norepinephrine.
      Adoptive transfer of T cells restores the blood pressure response to these
      stimuli. Agonistic antibodies to the ANG II receptor, produced by B cells,
      contribute to hypertension in experimental models of preeclampsia. The central
      nervous system seems important in immune cell activation, because lesions in the
      anteroventral third ventricle block hypertension and T cell activation in
      response to ANG II. Likewise, genetic manipulation of reactive oxygen species in
      the subfornical organ modulates both hypertension and immune cell activation.
      Current evidence indicates that the production of cytokines, including tumor
      necrosis factor-alpha, interleukin-17, and interleukin-6, contribute to
      hypertension, likely via effects on both the kidney and vasculature. In addition,
      the innate immune system also appears to contribute to hypertension. We propose a
      working hypothesis linking the sympathetic nervous system, immune cells,
      production of cytokines, and, ultimately, vascular and renal dysfunction, leading
      to the augmentation of hypertension. Studies of immune cell activation will
      clearly be useful in understanding this common yet complex disease. 

PMID- 24585469
TI  - Modified use of team-based learning in an ophthalmology course for fifth-year
      medical students.
AB  - Team-based learning (TBL) is an interactive and analytic teaching strategy. TBL
      is a learner-centered strategy that uses a very structured individual and group
      accountability process and requires small groups to work together to solve
      problems. This study served to investigate whether the TBL concept could be
      modified and adopted to the fifth-year cornea module of an ophthalmology course.
      Questionnaires (using a Likert scale of 1-5) were distributed to 169 fifth-year
      medical students attending the cornea module applied as TBL in an ophthalmology
      course. The questionnaire consisted of two categories: the TBL format (7 items)
      and an open-ended question about the class (1 item). Feedback was then evaluated.
      The majority of students felt that modified TBL sessions were better at
      fulfilling learning objectives (121 students, 71.59%), enabled better
      understanding (134 students, 79.28%), were more interesting (146 students,
      86.39%), ensured greater student participation (123 students, 72.78%), and
      involved greater effort on the part of students (148 students, 87.57%) compared
      with traditional teaching methods. Most of the students (129 students, 76.33%)
      agreed that more such sessions should be organized in the future. In conclusion,
      after adjustments to improve weaknesses, such as the short time allocation and
      students' lack of prior background, the outcomes of this modified TBL approach on
      the cornea module of an ophthalmology course provide a good basis for its
      continuation. 

PMID- 24585470
TI  - Making students do the thinking: team-based learning in a laboratory course.
AB  - Team-based learning (TBL) is a teaching pedagogy for flipping the classroom that
      moves the focus of the classroom from the instructor conveying course concepts
      via lecture to the application of concepts by student teams. It has been used
      extensively in lecture courses; however, there is little evidence of its use in
      laboratory courses. The purpose of this report is to describe the implementation
      of TBL in a graduate exercise physiology laboratory course. Using TBL in a
      graduate laboratory course was very successful and well received by both the
      students and instructor. Students reported increased content learning, skill
      development, and retention. They took on the responsibility for learning and were
      more accountable. The learners drove the process and were guided by the
      instructor rather than through instructor-centered delivery. 

PMID- 24585471
TI  - The summer premedical program for matriculating medical students: a student-led
      initiative.
AB  - The freshman academic year is one of the most difficult years that a medical
      student experiences in his/her academic life at a medical school. Freshmen are
      frequently faced with several challenges, such as adaptation to a new academic
      environment and its associated different methods of teaching, learning, skills,
      and assessment. The aim of this study was to describe a 4-wk innovative summer
      premedical program developed by senior medical students at the College of
      Medicine, Alfaisal University, in an attempt to improve/smooth the experience(s)
      of prospective freshmen. This report describes the
      objectives/strategies/methodologies used to tackle the top three identified
      freshman challenges, namely, 1) advancement of the
      academic/scholastic/educational background, 2) the development of college
      required skills to succeed and excel in the freshman year, and 3) adaption to the
      college environment. At the end of the program, a survey was conducted to
      evaluate the effectiveness of the summer premedical program. Seventy-two students
      attended this program over the past three summers from 2010 to 2012, and twenty
      nine students answered the survey with a response rate of 74.1%. Overall, >90% of
      the survey respondents reported an improvement in their understanding of basic
      medical science, integration, presentation skills, medical terminology, and
      junior-senior relationships. Furthermore, the survey highlighted the need for
      more focus on skills such as time management, participation in large-group
      discussions, and use of electronic resources, as >50% of respondents reported no
      improvement in these areas. In conclusion, this is the first report, to our
      knowledge, that describes a program developed by senior medical students to
      improve the experience of freshmen. 

PMID- 24585472
TI  - Portable conduction velocity experiments using earthworms for the college and
      high school neuroscience teaching laboratory.
AB  - The earthworm is ideal for studying action potential conduction velocity in a
      classroom setting, as its simple linear anatomy allows easy axon length
      measurements and the worm's sparse coding allows single action potentials to be
      easily identified. The earthworm has two giant fiber systems (lateral and medial)
      with different conduction velocities that can be easily measured by manipulating
      electrode placement and the tactile stimulus. Here, we present a portable and
      robust experimental setup that allows students to perform conduction velocity
      measurements within a 30-min to 1-h laboratory session. Our improvement over this
      well-known preparation is the combination of behaviorally relevant tactile
      stimuli (avoiding electrical stimulation) with the invention of minimal, low
      cost, and portable equipment. We tested these experiments during workshops in
      both a high school and college classroom environment and found positive learning
      outcomes when we compared pre- and posttests taken by the students. 

PMID- 24585473
TI  - Spiders in motion: demonstrating adaptation, structure-function relationships,
      and trade-offs in invertebrates.
AB  - Evolutionary history and structural considerations constrain all aspects of
      animal physiology. Constraints on invertebrate locomotion are especially
      straightforward for students to observe and understand. In this exercise,
      students use spiders to investigate the concepts of adaptation, structure
      function relationships, and trade-offs. Students measure burst and endurance
      performance in several taxonomic families of spiders whose ecological niches have
      led to different locomotory adaptations. Based on observations of spiders in
      their natural habitat and prior background information, students make predictions
      about spider performance. Students then construct their own knowledge by
      performing a hands-on, inquiry-based scientific experiment where the results are
      not necessarily known. Depending on the specific families chosen, students can
      observe that web-dwelling spiders have more difficulty navigating complex
      terrestrial terrain than ground-dwelling spiders and that there is a trade-off
      between burst performance and endurance performance in spiders. Our inexpensive
      runway design allows for countless variations on this basic experiment; for
      example, we have successfully used runways to show students how the performance
      of heterothermic ectotherms varies with temperature. High levels of intra- and
      interindividual variation in performance underscore the importance of using
      multiple trials and statistical tests. Finally, this laboratory activity can be
      completely student driven or standardized, depending on the instructor's
      preference. 

PMID- 24585474
TI  - Are all hands-on activities equally effective? Effect of using plastic models,
      organ dissections, and virtual dissections on student learning and perceptions.
AB  - This study investigated the impact of three commonly used cardiovascular model
      assisted activities on student learning and student attitudes and perspectives
      about science. College students enrolled in a Human Anatomy and Physiology course
      were randomly assigned to one of three experimental groups (organ dissections,
      virtual dissections, or plastic models). Each group received a 15-min lecture
      followed by a 45-min activity with one of the treatments. Immediately after the
      lesson and then 2 mo later, students were tested on anatomy and physiology
      knowledge and completed an attitude survey. Students who used plastic models
      achieved significantly higher overall scores on both the initial and followup
      exams than students who performed organ or virtual dissections. On the initial
      exam, students in the plastic model and organ dissection treatments scored higher
      on anatomy questions than students who performed virtual dissections. Students in
      the plastic model group scored higher than students who performed organ
      dissections on physiology questions. On the followup exam, when asked anatomy
      questions, students in the plastic model group scored higher than dissection
      students and virtual dissection students. On attitude surveys, organ dissections
      had higher perceived value and were requested for inclusion in curricula twice as
      often as any other activity. Students who performed organ dissections were more
      likely than the other treatment groups to agree with the statement that "science
      is fun," suggesting that organ dissections may promote positive attitudes toward
      science. The findings of this study provide evidence for the importance of
      multiple types of hands-on activities in anatomy laboratory courses. 

PMID- 24585475
TI  - The sympathetic release test: a test used to assess thermoregulation and
      autonomic control of blood flow.
AB  - When a subject is heated, the stimulation of temperature-sensitive nerve endings
      in the skin, and the raising of the central body temperature, results in the
      reflex release of sympathetic vasoconstrictor tone in the skin of the
      extremities, causing a measurable temperature increase at the site of release. In
      the sympathetic release test, the subject is gently heated by placing the feet
      and calves in a commercially available foot warming pouch or immersing the feet
      and calves in warm water and wrapping the subject in blankets. Skin blood flow is
      estimated from measurements of skin temperature in the fingers. Normally skin
      temperature of the fingers is 65-75 degrees F in cool conditions (environmental
      temperature: 59-68 degrees F) and rises to 85-95 degrees F during body heating.
      Deviations in this pattern may mean that there is abnormal sympathetic
      vasoconstrictor control of skin blood flow. Abnormal skin blood flow can
      substantially impair an individual's ability to thermoregulate and has important
      clinical implications. During whole body heating, the skin temperature from three
      different skin sites is monitored and oral temperature is monitored as an index
      of core temperature. Students determine the fingertip temperature at which the
      reflex release of sympathetic activity occurs and its maximal attainment, which
      reflects the vasodilating capacity of this cutaneous vascular bed. Students
      should interpret typical sample data for certain clinical conditions (Raynaud's
      disease, peripheral vascular disease, and postsympathectomy) and explain why
      there may be altered skin blood flow in these disorders. 

PMID- 24585476
TI  - Physiology applied to everyday: the practice of professional contextualization of
      physiology concepts as a way of facilitating learning.

PMID- 24585477
TI  - Supporting physiology learning: the development of interactive concept-based
      video clips.

PMID- 24585478
TI  - Is it hot in here? Thermoregulation and homeostasis through an exercise activity.

PMID- 24585479
TI  - Collaborative strategies for teaching common acid-base disorders to medical
      students.

PMID- 24585480
TI  - Design and use of a proton pump inhibitor case to integrate physiology,
      pharmacology, and biochemistry.

PMID- 24585481
TI  - Heteroatom substituted organic/polymeric semiconductors and their applications in
      field-effect transistors.
AB  - Organic/polymeric semiconductors are mainly composed of aromatic systems
      including phenyl, vinyl, alkynyl, thienyl, and other isoelectric groups, which
      are constructed of carbon, hydrogen, and so-called 'hereroatoms' including
      chalcogen, nitrogen, and halogen atoms etc. The introduction of heteroatoms could
      yield different electronic properties by influencing the molecular geometry, the
      HOMO and LUMO energy levels, intermolecular interactions and so on. In this
      Research News article, we provide a brief review of the effect of heteroatoms and
      recent developments in heteroatom substituted organic/polymeric semiconductors,
      focusing especially on their application in field-effect transistors. 

PMID- 24585482
TI  - Formal education of patients about to undergo laparoscopic cholecystectomy.
AB  - BACKGROUND: Generally, before being operated on, patients will be given informal
      information by the healthcare providers involved in the care of the patients
      (doctors, nurses, ward clerks, or healthcare assistants). This information can
      also be provided formally in different formats including written information,
      formal lectures, or audio-visual recorded information. OBJECTIVES: To compare the
      benefits and harms of formal preoperative patient education for patients
      undergoing laparoscopic cholecystectomy. SEARCH METHODS: We searched the Cochrane
      Central Register of Controlled Trials (CENTRAL) (Issue 2, 2013), MEDLINE, EMBASE,
      and Science Citation Index Expanded to March 2013. SELECTION CRITERIA: We
      included only randomised clinical trials irrespective of language and publication
      status. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted
      the data. We planned to calculate the risk ratio with 95% confidence intervals
      (CI) for dichotomous outcomes, and mean difference (MD) or standardised mean
      difference (SMD) with 95% CI for continuous outcomes based on intention-to-treat
      analyses when data were available. MAIN RESULTS: A total of 431 participants
      undergoing elective laparoscopic cholecystectomy were randomised to formal
      patient education (215 participants) versus standard care (216 participants) in
      four trials. The patient education included verbal education, multimedia DVD
      programme, computer-based multimedia programme, and Power Point presentation in
      the four trials. All the trials were of high risk of bias. One trial including
      212 patients reported mortality. There was no mortality in either group in this
      trial. None of the trials reported surgery-related morbidity, quality of life,
      proportion of patients discharged as day-procedure laparoscopic cholecystectomy,
      the length of hospital stay, return to work, or the number of unplanned visits to
      the doctor. There were insufficient details to calculate the mean difference and
      95% CI for the difference in pain scores at 9 to 24 hours (1 trial; 93 patients);
      and we did not identify clear evidence of an effect on patient knowledge (3
      trials; 338 participants; SMD 0.19; 95% CI -0.02 to 0.41; very low quality
      evidence), patient satisfaction (2 trials; 305 patients; SMD 0.48; 95% CI -0.42
      to 1.37; very low quality evidence), or patient anxiety (1 trial; 76
      participants; SMD -0.37; 95% CI -0.82 to 0.09; very low quality evidence) between
      the two groups.A total of 173 participants undergoing elective laparoscopic
      cholecystectomy were randomised to electronic consent with repeat-back (patients
      repeating back the information provided) (92 participants) versus electronic
      consent without repeat-back (81 participants) in one trial of high risk of bias.
      The only outcome reported in this trial was patient knowledge. The effect on
      patient knowledge between the patient education with repeat-back versus patient
      education without repeat-back groups was imprecise and based on 1 trial of 173
      participants; SMD 0.07; 95% CI -0.22 to 0.37; very low quality evidence).
      AUTHORS' CONCLUSIONS: Due to the very low quality of the current evidence, the
      effects of formal patient education provided in addition to the standard
      information provided by doctors to patients compared with standard care remain
      uncertain. Further well-designed randomised clinical trials of low risk of bias
      are necessary.

PMID- 24585483
TI  - Influence of parity on fetal hemodynamics and amniotic fluid volume at term.
AB  - OBJECTIVES: Pregnancy complications, particularly those associated with placental
      dysfunction, occur more frequently in nulliparous than in parous women. This
      difference may be a consequence of improved trophoblastic invasion and, as a
      result, improved placental function following previous pregnancy. Placental
      dysfunction in cases of fetal growth restriction may be identified by ultrasound
      assessment of fetoplacental hemodynamics and amniotic fluid volume. In this
      prospective observational study, we investigated whether differences in these
      measures of placental function exist between nulliparous and parous women, prior
      to active labor. METHODS: Over a 2-year period, 456 nulliparous and 152 parous
      women with uncomplicated singleton pregnancies were recruited to this prospective
      observational study. Each participant underwent an ultrasound assessment prior to
      active labor, during which fetal biometry, umbilical artery, middle cerebral
      artery and umbilical venous Dopplers, as well as amniotic fluid volume, were
      assessed. All cases were followed up within 48 h of delivery. Ultrasound
      parameters and intrapartum outcomes were then compared between the nulliparous
      and parous groups. RESULTS: Compared with nulliparous women, parous women had
      significantly higher fetal middle cerebral artery pulsatility index,
      cerebroplacental ratio and amniotic fluid volume. In nulliparous women, middle
      cerebral artery flow rate was also significantly higher and represented a greater
      percentage of umbilical venous flow than was observed in parous women.
      CONCLUSION: Prior to the active phase of labor, ultrasound parameters indicative
      of placental function differ significantly between nulliparous and parous
      pregnancy, even amongst an uncomplicated, low-risk cohort.

PMID- 24585484
TI  - Cranial sonography in extremely preterm infants.
AB  - Survival rates of extremely preterm infants have risen dramatically, paralleling
      improvements in prenatal and neonatal care. Cranial sonography is the primary
      imaging technique for the evaluation of brain injury in these patients. Extremely
      preterm infants have some unique features related to ongoing maturation, and
      associated findings on cranial sonography should be considered for accurate and
      early diagnosis. The aim of this pictorial essay is to illustrate normal anatomy,
      normal variants, and pitfalls that lead to misinterpretation of cranial
      sonography in extremely preterm infants.

PMID- 24585485
TI  - The Russian Society of Cardiology.

PMID- 24585486
TI  - Safety analysis of Ziagen(r) (abacavir sulfate) in postmarketing surveillance in
      Japan.
AB  - PURPOSE: Abacavir is a nucleoside reverse transcriptase inhibitor indicated for
      human immunodeficiency virus (HIV) infection. In Japan, Ziagen(r) (300-mg
      abacavir sulfate) has been marketed since 1999. To obtain safety data on Ziagen,
      a mandatory postmarketing surveillance was conducted between September 1999 and
      September 2009. METHODS: A joint survey [HIV-related Drug Surveys (HRD)] has been
      conducted involving manufacturers of drugs for HIV treatment in Japan. Safety
      data from total 643 cases (1345.7 person-years) registered to the HRD surveys and
      received Ziagen were obtained. Adverse drug reaction (ADR) was defined as adverse
      event of which association with abacavir could not be "ruled out." RESULTS: It
      was found that the overall frequency of ADR was 47.6% (306/643); the common ADRs
      were "hyperlipidemia," "nausea," "increased gamma-glutamyltransferase level,"
      "increased blood triglycerides," "abnormal hepatic function," and so on. Serious
      adverse events were reported in 65 subjects; however, none of the three fatal
      cases were clearly associated with Ziagen use. The survey-defined
      hypersensitivity has been infrequently reported in 15 subjects (2.3%). Although
      some studies had indicated of the association between abacavir and myocardial
      infarction, no ischemic heart diseases were reported in the present survey. Two
      of the three pregnant cases delivered normal neonates (one induced abortion).
      CONCLUSIONS: During the mandatory postmarketing survey of Ziagen, there were no
      cases of ischemic heart diseases, and the incidence of hypersensitivity was
      considerably low. These indicated that abacavir can be safely used in Japanese
      HIV+ population. However, the safety profile of Ziagen should be continued to be
      monitored through pharmacovigilance.

PMID- 24585487
TI  - Improving chemical shift encoded water-fat separation using object-based
      information of the magnetic field inhomogeneity.
AB  - PURPOSE: The purpose of this work was to improve the robustness of existing
      chemical shift encoded water-fat separation methods by incorporating object-based
      information of the B0 field inhomogeneity. THEORY: The primary challenge in water
      fat separation is the estimation of phase shifts that arise from B0 field
      inhomogeneity, which is composed of the background field and susceptibility
      induced field. The susceptibility-induced field can be estimated if the
      susceptibility distribution is known or can be approximated. In this work, the
      susceptibility distribution is approximated from the source images using the
      known susceptibility values of water, fat, and air. The field estimate is then
      demodulated from the source images before water-fat separation. METHODS: Chemical
      shift encoded source images were acquired in anatomical regions that are prone to
      water-fat swaps. The images were processed using algorithms from the ISMRM Fat
      Water Toolbox, with and without the object-based field map information. The
      estimates were compared to examine the benefit of using the object-based field
      map information. RESULTS: Multiple cases are shown in which water-fat swaps were
      avoided by using the object-based information of the B0 field map. CONCLUSION:
      Object-based information of the B0 field may improve the robustness of existing
      chemical shift encoded water-fat separation methods.

PMID- 24585488
TI  - Late HDV RNA relapse after peginterferon alpha-based therapy of chronic hepatitis
      delta.
AB  - Interferon alpha is the only treatment option for hepatitis delta virus (HDV).
      Trials investigating the efficacy of pegylated interferon alpha (PEG-IFNa) showed
      HDV RNA negativity rates of 25-30% 24 weeks after therapy. However, the clinical
      and virological long-term outcome of HDV-infected patients treated with PEG-IFNa
      is unknown. We performed a retrospective-prospective follow-up of 77 patients
      treated for 48 weeks with either PEG-alfa-2a and adefovir (ADV) or either drug
      alone in the Hep-Net-International-Delta-Hepatitis-Intervention-Study 1 (HIDIT-1)
      trial. Long-term follow-up data were available for 58 out of 77 patients (75%)
      with a median time of follow-up of 4.5 (0.5-5.5) years and a median 3 visits per
      patient. Patients treated with ADV alone received retreatment with PEG-IFNa (48%
      versus 19%; P = 0.02) more often. Hepatitis B virus surface antigen (HBsAg)
      became negative in six PEG-IFNa-treated patients until the end of long-term
      follow-up (10%). Sixteen patients tested HDV RNA-negative 6 months after PEG-IFNa
      treatment who were entered in the long-term follow-up study. Out of these, nine
      individuals tested HDV RNA-positive at least once during further long-term follow
      up, with seven patients being HDV RNA-positive at the most recent visit. Clinical
      endpoints (liver-related death, liver transplantation, hepatic decompensation,
      hepatocellular carcinoma) were observed in three PEG-IFNa-treated (8%) and three
      ADV-treated (14%) patients during posttreatment long-term follow-up with an
      overall annual event rate of 2.5% (4.9% in cirrhosis). Sequencing confirmed the
      reappearance of pretreatment virus strains in all cases. CONCLUSION: Late HDV RNA
      relapses may occur after PEG-IFNa therapy of hepatitis delta and thus the term
      sustained virological response should be avoided in HDV infection. The annual
      posttreatment rate of clinical events in hepatitis delta patients eligible for
      PEG-IFNa therapy is about 2.5% and 4.9% in patients with cirrhosis.

PMID- 24585489
TI  - Keeping rotavirus vaccines on the international agenda.

PMID- 24585493
TI  - Percutaneous mechanical assist for severe cardiogenic shock due to acute right
      ventricular failure.
AB  - Acute right ventricular failure can lead to severe cardiogenic shock and death.
      Recovery may be achieved with early supportive measures. In many patients,
      intravenous fluid and inotropic resuscitation is inadequate to improve cardiac
      output. In these cases, percutaneous mechanical assist may provide a non-surgical
      bridge to recovery. Herein, we describe a case series of patients with severe,
      refractory cardiogenic shock due to acute right ventricular failure who received
      a continuous flow percutaneous ventricular device primarily utilizing the right
      internal jugular vein for out flow cannula placement.

PMID- 24585490
TI  - Association study of a functional copy number variation in the WWOX gene with
      risk of gliomas among Chinese people.
AB  - Gliomas represents more than 80% of all malignant brain tumors. However, the
      etiology still remains largely unknown. Human WW domain-containing oxidoreductase
      (WWOX), which is located at 16q23.1-16q23.2, the common fragile site 16D
      (FRA16D), an area with a high frequency of gene deletions or chromosomal
      alterations, has been identified as a tumor suppressor gene in multiple cancers.
      In current study, we analyzed the WWOX deletion (CNV-67048) in a large, case
      control study of 3,622 adult Chinese people (including 1,798 glioma cases and
      1,824 healthy controls). All participants were genotyped using real-time
      qualitative PCR (qPCR), and its biological effect was validated with mRNA
      expression assays. The deletion was significantly associated with glioma risk,
      with ORs (95% CIs) of 1.21 (1.05-1.41) associated with 1 copy deletion and 1.94
      (1.37-2.75) associated with 2 copy deletion as compared with subjects with no
      deletion (p for trend = 8.05 * 10(-6)). Additional adjustments and stratified
      analyses did not change the results materially. The mRNA levels of WWOX in glioma
      tissues were significantly lower than that of their border tissues (p = 0.007),
      especially in the loss genotyped subjects. Our data suggest that the loss
      genotypes of CNV-67048 in WWOX gene predispose their carriers to gliomas, and
      WWOX gene deletion may be a new biomarker for predicting risk of gliomas.

PMID- 24585494
TI  - Abnormal non-invasive prenatal test results concordant with karyotype of
      cytotrophoblast but not reflecting abnormal fetal karyotype.
AB  - We present a unique case in which non-invasive and invasive prenatal diagnoses
      showed abnormal, but discordant, results. A patient with abnormal non-invasive
      prenatal test (NIPT) results, indicating a 99% risk for monosomy X, was referred
      to our center for genetic counseling and confirmatory studies. Cytogenetic
      analysis of uncultured mesenchymal core of chorionic villi (CV) revealed a mosaic
      male karyotype consisting of two abnormal cell lines: one with monosomy X and the
      other with an isodicentric chromosome Y. Array analysis of the trophoblast
      confirmed the NIPT results. Based on the CV results, the patient opted for
      termination of pregnancy. After extensive counseling by a clinical geneticist
      about the possible outcomes and by a gynecologist about the risk of a second
      trimester abortion procedure, the patient agreed to undergo early amniocentesis.
      Amniocentesis confirmed that the fetus had a male karyotype with an isodicentric
      chromosome Y, and the single nucleotide polymorphism (SNP) array profile
      suggested absence of the monosomy X cell line. The male infant was expected to be
      infertile. The patient finally decided to continue the pregnancy. Our case
      confirms that NIPT results are comparable with those of short-term cultured CV
      investigating the cytotrophoblast. Our patient was not aware that the NIPT
      results reveal the placental karyotype, which sometimes may be different from the
      fetal karyotype. Pretest counseling and providing the risk figures for false
      positive and false-negative NIPT results are of great importance in order to
      discourage women from terminating pregnancies based on NIPT results alone.

PMID- 24585495
TI  - Testicular microlithiasis: prevalence and association with primary testicular
      neoplasm.
AB  - PURPOSE: To assess the prevalence of testicular microlithiasis and its
      association with primary testicular neoplasm. METHODS: Evaluated were 6,002
      patients undergoing scrotal ultrasound at our institution. Data recorded included
      age, ultrasound date, presence of microlithiasis, presence of testicular mass on
      ultrasound, and pathologic diagnosis for those who had subsequent orchiectomy.
      RESULTS: Four hundred fifty-six of 6,002 patients (7.6%) demonstrated testicular
      microlithiasis. The prevalence increased from 4.6% for those examined before 2001
      to 9.02% for those examined since 2001 (p < 0.001). The prevalence of primary
      testicular neoplasm in patients without microlithiasis was 1.5% (84/5,546),
      whereas in those with microlithiasis it was 12% (53/456) (p < 0.001). The
      prevalence of pure seminoma was 39% (33/84) in the nonmicrolithiasis group with
      tumor versus 64% (34/53) in the microlithiasis group with tumor (p < 0.001). Germ
      cell tumors made up 98% of neoplasms in patients with microlithiasis, but only
      85% in patients without microlithiasis (p = 0.009). CONCLUSIONS: Advances in
      ultrasound technology have led to an increased detection of testicular
      microlithiasis. We observed an eight-fold increased prevalence of primary
      testicular neoplasm in patients with microlithiasis than in those without as well
      as an increased prevalence of germ cell tumors, particularly pure seminoma. (c)
      2014 Wiley Periodicals, Inc. J Clin Ultrasound 42:423-426, 2014.

PMID- 24585496
TI  - Classification of Spanish white wines using their electrophoretic profiles
      obtained by capillary zone electrophoresis with amperometric detection.
AB  - A method was developed for the simultaneous detection of eight polyphenols (t
      resveratrol, (+)-catechin, quercetin and p-coumaric, caffeic, sinapic, ferulic,
      and gallic acids) by CZE with electrochemical detection. Separation of these
      polyphenols was achieved within 25 min using a 200 mM borate buffer (pH 9.4)
      containing 10% methanol as separation electrolyte. Amperometric detection of
      polyphenols was carried out with a glassy carbon electrode (GCE) modified with a
      multiwalled carbon nanotubes (CNT) layer obtained from a dispersion of CNT in
      polyethylenimine. The excellent electrochemical properties of this modified
      electrode allowed the detection and quantification of the selected polyphenols in
      white wines without any pretreatment step, showing remarkable signal stability
      despite the presence of potential fouling substances in wine. The electrophoretic
      profiles of white wines, obtained using this methodology, have proven to be
      useful for the classification of these wines by means of chemometric multivariate
      techniques. Principal component analysis and discriminant analysis allowed
      accurate classification of wine samples on the basis of their grape varietal
      (verdejo and airen) using the information contained in selected zones of the
      electropherogram. The utility of the proposed CZE methodology based on the
      electrochemical response of CNT-modified electrodes appears to be promising in
      the field of wine industry and it is expected to be successfully extended to
      classification of a wider range of wines made of other grape varietals. 

PMID- 24585497
TI  - Graphene-like single-layered covalent organic frameworks: synthesis strategies
      and application prospects.
AB  - Two-dimensional (2D) nanomaterials, such as graphene and transition metal
      chalcogenides, show many interesting dimension-related materials properties.
      Inspired by the development of 2D inorganic nanomaterials, single-layered
      covalent organic frameworks (sCOFs), featuring atom-thick sheets and crystalline
      extended organic structures with covalently bonded building blocks, have
      attracted great attention in recent years. With their unique graphene-like
      topological structure and the merit of structural diversity, sCOFs promise to
      possess novel and designable properties. However, the synthesis of sCOFs with
      well-defined structures remains a great challenge. Herein, the recent development
      of the bottom-up synthesis methods of 2D sCOFs, such as thermodynamic equilibrium
      control methods, growth-kinetics control methods, and surface-assisted covalent
      polymerization methods, are reviewed. Finally, some of the critical properties
      and application prospects of these materials are outlined. 

PMID- 24585498
TI  - Omega 3 fatty acids (fish oil) for maintenance of remission in Crohn's disease.
AB  - BACKGROUND: The anti-inflammatory effects of n-3 (omega-3 fatty acids, fish oil)
      have been suggested to be beneficial in chronic inflammatory disorders such as
      inflammatory bowel disease. This review is an update of a previously published
      Cochrane review. OBJECTIVES: To systematically review the efficacy and safety of
      n-3 for maintenance of remission in Crohn's disease (CD). SEARCH METHODS: The
      following databases were searched from inception to November 2013 without
      language restriction: CENTRAL, MEDLINE, EMBASE, HealthSTAR, PubMed, and ACP
      journal club. SELECTION CRITERIA: Randomized placebo-controlled trials (RCT) of n
      3 for maintenance of remission in CD were included. Studies must have enrolled
      patients of any age group, who were in remission at the time of recruitment, and
      were followed for at least six months. The intervention must have been fish oil
      or n-3 given in pre-defined dosage. Co-interventions were allowed only if they
      were balanced between the study groups. DATA COLLECTION AND ANALYSIS: The primary
      outcome was the relapse rate and secondary outcomes included change in disease
      activity scores, time to first relapse and adverse events. Two independent
      investigators reviewed studies for eligibility, extracted the data and assessed
      study quality using the Cochrane risk of bias tool. The overall quality of the
      evidence supporting the primary and selected secondary outcomes was reassessed
      for the current update using the GRADE system. We used the RevMan software for
      analyses. We calculated the risk ratio (RR) and corresponding 95% confidence
      interval (CI) for dichotomous outcomes and the hazard ratio and 95% CI for time
      to-event outcomes. Random-effects or fixed-effect models were used according to
      degree of heterogeneity and sensitivity analyses were performed in an attempt to
      explore possible sources of heterogeneity. MAIN RESULTS: Six studies with a total
      of 1039 patients were eligible for inclusion. The two largest studies were rated
      as low risk of bias for all assessed items. Four studies were rated as unclear
      risk of bias for randomization and allocation concealment. Two studies were rated
      as high risk of bias for incomplete outcome data and selective reporting. There
      was a marginal significant benefit of n-3 therapy for maintenance of remission.
      Thirty-nine per cent of patients in the n-3 group relapsed at 12 months compared
      to 47% of placebo patients (6 studies, 1039 patients; RR 0.77, 95% CI 0.61 to
      0.98). A GRADE analysis rated the overall quality of the evidence for the primary
      outcome (i.e. relapse) as very low due to unexplained heterogeneity (I2 = 58%),
      publication bias, and a high or unknown risk of bias in four studies in the
      pooled analysis. When two large studies at low risk of bias were considered the
      benefit was no longer statistically significant. Thirty-seven per cent of
      patients in the n-3 group relapsed at 12 months compared to 42% of placebo
      patients (2 studies, 738 patients; RR 0.88, 95% CI 0.74 to 1.05). No significant
      heterogeneity was identified for this pooled analysis ( I2 = 0%). A GRADE
      analysis indicated that the overall quality of the evidence supporting this
      outcome was moderate due to sparse data (294 events). No serious adverse events
      were recorded in any of the studies but in a pooled analyses there was a
      significantly higher rate of diarrhea (4 studies, 862 patients; RR 1.36 95% CI
      1.01 to 1.84) and upper gastrointestinal tract symptoms (5 studies, 999 patients;
      RR 1.65, 95% CI 1.25 to 2.18) in the n-3 treatment group. AUTHORS' CONCLUSIONS:
      Evidence from two large high quality studies suggests that omega 3 fatty acids
      are probably ineffective for maintenance of remission in CD. Omega 3 fatty acids
      appear to be safe although they may cause diarrhea and upper gastrointestinal
      tract symptoms.

PMID- 24585499
TI  - Rare malignant pediatric tumors registered in the German Childhood Cancer
      Registry 2001-2010.
AB  - BACKGROUND: The German Childhood Cancer Registry (GCCR) annually registers
      approximately 2,000 children diagnosed with a malignant disease (completeness of
      registration >95%). While most pediatric cancer patients are diagnosed and
      treated according to standardized cooperative protocols of the German Society for
      Pediatric Oncology and Hematology (GPOH), patients with rare tumors are at risk
      of not being integrated in the network including trials and reference centers.
      PROCEDURE: A retrospective analysis of all rare extracranial solid tumors
      reported to the GCCR 2001-2010 (age <18 years) was undertaken using a combination
      of the International Classification of Childhood Cancer (ICCC-3) and the
      International Classification of Diseases-Oncology (ICD-O-3). Tumors accounting
      for <0.3% of all malignancies were defined as rare (approx. 6 cases/year and
      registered malignancy). RESULTS: According to this definition 1,189 rare
      extracranial solid tumors (18.2% of all malignant extracranial solid tumors) were
      registered, among these 232 patients (19.5% of rare tumor cases), were not
      included in preexisting GPOH studies/registries. Within 10 years, the number of
      registered non-GPOH-trial patients with a rare tumor increased. CONCLUSIONS:
      Though most of the GCCR-registered patients with rare malignant tumors are
      treated within GPOH trials, there is a considerable number of patients that have
      been diagnosed and treated outside the structures of the GPOH. These patients
      should be reported to the recently founded German Pediatric Rare Tumor Registry
      (STEP). Active data accrual and the development of appropriate structures will
      allow for better registration and improvement of medical care in these patients.

PMID- 24585500
TI  - Group vs. single mindfulness meditation: exploring avoidance, impulsivity, and
      weight management in two separate mindfulness meditation settings.
AB  - Recent research has identified that mindfulness meditation in group settings
      supports people who are trying to lose weight. The present research investigated
      mindfulness meditation in group and individual settings, and explored the
      potential impact on weight loss and other factors (i.e. mindfulness, impulsivity,
      and avoidance) that may assist or hinder weight loss. Specifically, the
      hypotheses tested were that the group setting assisted dieters more than the
      individual setting by reducing weight, cognitive-behavioral avoidance, and
      impulsivity and by increasing mindfulness. Participants (n = 170) who were trying
      to lose weight were randomly assigned to practice meditation for 6 weeks within a
      group or independently. Measurements in mindfulness, cognitive-behavioral
      avoidance, impulsivity, and weight occurred twice (pre- and post-intervention).
      Results indicated that participants in the group setting lost weight and lowered
      their levels of cognitive-behavioral avoidance, while impulsivity and mindfulness
      remained stable. On the other hand, participants in the individual condition lost
      less weight, while there was an increase in cognitive-behavioral avoidance and
      mindfulness scores, but a decrease in impulsivity. Seeing that benefits and
      limitations observed in group settings are not replicated when people meditate
      alone, this study concluded that mindfulness meditation in individual settings
      needs to be used with caution, although there are some potential benefits that
      could aid future weight loss research.

PMID- 24585501
TI  - Crown-rump length discordance and adverse perinatal outcome in twin pregnancies:
      systematic review and meta-analysis.
AB  - OBJECTIVE: The aim of this systematic review was to explore the relationship
      between crown-rump length (CRL) discordance detected at 11-14 weeks of gestation
      and adverse outcome in twin pregnancy and to assess its predictive accuracy.
      METHODS: A protocol designed a priori following MOOSE guidelines and recommended
      for systematic review and meta-analysis was used. The outcomes observed were:
      total fetal and perinatal loss, fetal loss at <24 weeks, fetal loss at >= 24
      weeks, birth-weight (BW) discordance, preterm delivery (PTD) at < 34 weeks and
      fetal anomalies. The analysis was performed for all twins and for dichorionic
      (DC) and monochorionic (MC) twins separately. RESULTS: A total of 2008 articles
      were identified and 17 studies were included in the systematic review. Twin
      pregnancies with CRL discordance >= 10% were at significantly higher risk of
      perinatal loss (RR, 2.80; 95% CI, 1.25-6.27; P = 0.012), fetal loss at >= 24
      weeks (RR, 4.07; 95% CI, 1.47-11.23; P = 0.006), BW discordance (RR, 2.24; 95%
      CI, 1.89-2.64; P < 0.001) and PTD at < 34 weeks (RR, 1.49; 95% CI, 1.23-1.80; P <
      0.001) but not of fetal loss at < 24 weeks (P = 0.130). A meta-analysis of fetal
      anomalies was not possible because fewer than two studies explored this outcome.
      However, when used alone to screen for adverse pregnancy outcome, the predictive
      accuracy of CRL discordance was low for each of the outcomes explored.
      CONCLUSION: CRL discordance is associated with an increased risk of adverse
      pregnancy outcome. However, the accuracy of CRL discordance in predicting adverse
      outcome is poor and thus limits its routine use in clinical practice.

PMID- 24585502
TI  - Complex patients treated with zotarolimus-eluting resolute and everolimus-eluting
      Xience V stents in the randomized TWENTE trial: comparison of 2-year clinical
      outcome.
AB  - OBJECTIVE: To assess the differences in clinical outcome between complex patients
      treated with Resolute zotarolimus-eluting stents (ZES) versus Xience V everolimus
      eluting stents (EES). BACKGROUND: Nowadays, many complex patients with coronary
      disease are treated with percutaneous coronary interventions, using drug-eluting
      stents (DES). METHODS: We analyzed 2-year outcome data of 1,033 complex patients
      of the TWENTE trial, treated with second-generation Resolute ZES or Xience V EES.
      Complex patients had at least one of the following characteristics: renal
      insufficiency (creatinine >= 140 umol/l); ejection fraction < 30%; acute
      myocardial infarction (MI) within previous 72 hrs; >1 lesion/vessel; >2 vessels
      treated; lesion length > 27 mm; bifurcation; saphenous vein graft lesion;
      arterial bypass graft lesion; in-stent restenosis; unprotected left main lesion;
      lesion with thrombus; or lesion with total occlusion. Target vessel failure
      (TVF), the primary composite endpoint of the trial, was defined as cardiac death,
      target vessel-related MI, or target vessel revascularization. RESULTS: Among the
      1,033 complex patients, 529 (51%) were treated with Resolute ZES and 504 (49%)
      with Xience V EES. Patient- and procedure-related characteristics were similar
      between DES groups. After 2-year follow-up, outcome was also similar between DES
      groups. TVF occurred in 12.1% of patients treated with Resolute ZES and 12.3% of
      patients treated with Xience V EES. In addition, DES groups did not differ
      significantly in cardiac death, MI, or target vessel revascularization-the
      individual components of TVF. CONCLUSION: Complex patients treated with Resolute
      ZES and Xience V EES showed similar safety and efficacy during 2-year follow-up.
      (c) 2014 Wiley Periodicals, Inc.

PMID- 24585503
TI  - Computerized physician order entry-based system to prevent HBV reactivation in
      patients treated with biologic agents: the PRESCRIB project.
AB  - Computerized physician order entry (CPOE) applications are widely used to prevent
      medical errors. In our center, a CPOE system has been in use since 2009 on both
      the inpatient and outpatient levels. A new and simple alert was introduced in the
      CPOE system to notify healthcare providers of the potential risk of viral
      reactivation when prescribing biological therapies, thereby facilitating the
      request for a serological profile (hepatitis B surface antigen [HBsAg], anti-HBc,
      and anti-HBs) in patients who have not had these tests. Between May 2012 and May
      2013, a total of 1,076 patients undergoing biological treatment were included in
      the implementation of the CPOE in our hospital, resulting in the identification
      of 4 HBsAg-positive and 69 anti-HBc-positive/HBsAg-negative patients, two of them
      with positive viral loads. Since the implementation of this alert system, over
      90% of patients who were prescribed a biological drug (BD) have undergone
      serological screening to detect hepatitis B virus (HBV) infection. The use of the
      alert system has increased the screening rate from less than 50% to 94% for HBsAg
      and from less than 30% to 85% for anti-HBc in patients for whom a BD is
      prescribed. Six patients received prophylactic antiviral therapy. No patient had
      HBV reactivation. CONCLUSION: This study demonstrates the feasibility of
      implementing a CPOE system that has allowed our hospital to increase the rate of
      HBV screening. Its use has facilitated the identification of patients at high
      risk for HBV reactivation and permitted physicians to prescribe prophylactic
      measures according to current guidelines.

PMID- 24585505
TI  - Catechin concentrates of garden tea leaves (Camellia sinensis L.):
      extraction/isolation and evaluation of chemical composition.
AB  - BACKGROUND: Solid-liquid (SLE) and liquid-liquid (LLE) extraction techniques were
      applied to extract catechins and caffeine from quick mechanically expelled tea
      leaf juice (QMETLJ) and freeze-dried (FD)-QMETLJ of Camellia sinensis L. The
      concentrates obtained were analyzed for total polyphenol content and antioxidant
      activity (DPPH(*) inhibition, FRAP and phosphomolybdenum assay). Catechins were
      identified and quantified using HPLC. RESULTS: Overall, 95% (v/v) ethanol was the
      best solvent system for extracting total polyphenols (355.26 +/- 23.68 to 457.89
      +/- 28.94 g GAE kg(-1) extractable solid yield (ESY)) and antioxidants (DPPH(*)
      inhibition, 16.97 +/- 0.52 to 20.83 +/- 3.11%; FRAP, 4.15 +/- 0.32 to 6.38 +/-
      0.57 mmol TE g(-1) ESY; Mo(V) reduction, 2.47 +/- 0.19 to 3.84 +/- 0.39 mmol AAE
      g(-1) ESY) from FD-QMETLJ. Similarly, in LLE, ethyl acetate showed the best
      results for recovering polyphenols (960.52 +/- 7.89 g GAE kg(-1) ESY) and
      antioxidants (DPPH(*) inhibition, 42.39 +/- 0.91%; FRAP, 11.39 +/- 0.83 mmol TE
      g(-1) ESY; Mo(V) reduction, 6.71 +/- 1.14 mmol AAE g(-1) ESY) from QMETLJ.
      CONCLUSION: It was found that 95% ethanol can be used to increase the total
      polyphenols and antioxidants in extracts from FD-QMETLJ, while ethyl acetate can
      be effectively employed for concentrating catechins from QMETLJ.

PMID- 24585506
TI  - Phase II study of gefitinib in patients with advanced salivary gland cancers.
AB  - BACKGROUND: The purpose of this study was to determine the antitumor activity of
      the epidermal growth factor receptor (EGFR) inhibitor gefitinib in patients with
      recurrent/metastatic salivary gland cancer. METHODS: We conducted a phase II
      study in adenoid cystic carcinoma (ACC) and non-ACC. Gefitinib was administered
      250 mg orally daily. The primary endpoint was tumor response. Secondary endpoints
      included progression-free survival (PFS), overall survival (OS), and disease
      control rates. EGFR and human epidermal growth factor receptor 2 (HER2)
      expression were evaluated and correlated with outcomes. RESULTS: Thirty-seven
      patients were enrolled in this study, and 36 were evaluable (18 with ACC and 18
      with non-ACC). No responses were observed. Median PFS was 4.3 months and 2.1
      months, and median OS was 25.9 months and 16 months for patients with ACC and non
      ACC, respectively. The disease control rate at 8 weeks was higher in patients
      with ACC. No unexpected toxicities occurred. EGFR and HER2 overexpression did not
      correlate with outcomes. CONCLUSION: We did not observe significant clinical
      activity of gefitinib in advanced salivary gland cancer. NCT00509002.

PMID- 24585507
TI  - Reliability of estimated glomerular filtration rate in patients treated with
      platinum containing therapy.
AB  - Estimates of glomerular filtration rate (eGFR) are widely used when administering
      nephrotoxic chemotherapy. No studies performed in oncology patients have shown
      whether eGFR can safely substitute a measured GFR (mGFR) based on a marker
      method. We aimed to assess the validity of four major formulas based on PCr
      (Cockcroft-Gault, MDRD, Wright and CKD-EPI) in comparison to mGFR in an oncology
      setting. Patients included had disseminated germ cell cancer and received
      conventional chemotherapy: bleomycin, etoposide and cisplatin. The mGFR of the
      patients was compared to all estimates with focus on bias (median percentage
      error), precision (median absolute percentage error) and accuracy (p10 and p30).
      The precision of carboplatin dosage based on eGFR was calculated. Data on mGFR,
      eGFR, and PCr were available in 390 patients, with a total of ~ 1,600
      measurements. Median PCr and mGFR synchronically decreased after chemotherapy,
      yielding high bias and low precision of most estimates. Post-chemotherapy, bias
      ranged from -0.2% (MDRD after four cycles) to 33.8% (CKD-EPI after five cycles+),
      precision ranged from 11.6% (MDRD after four cycles) to 33.8% (CKD-EPI after five
      cycles+) and accuracy (p30) ranged from 37.5% (CKD-EPI after five cycles+) to
      86.9% (MDRD after four cycles). Although MDRD appeared acceptable after
      chemotherapy because of high accuracy, this equation underestimated GFR in all
      other measurements. Before and years after treatment, Cockcroft-Gault and Wright
      offered best results. Precision of carboplatin dosage was low. In conclusion,
      bias, precision and accuracy were unacceptable in all equations due to a
      synchronous decrease of PCr and mGFR during chemotherapy.

PMID- 24585508
TI  - The efficacy of "hybrid" percutaneous coronary intervention in chronic total
      occlusions caused by in-stent restenosis: insights from a US multicenter
      registry.
AB  - OBJECTIVES: To examine the success and complication rates in percutaneous
      coronary intervention (PCI) for chronic total occlusions (CTO) caused by in-stent
      restenosis (ISR). BACKGROUND: PCI for in-stent total occlusive disease has
      traditionally been associated with low success rates. We sought to examine
      angiographic and procedural outcomes of patients who underwent CTO PCI due to ISR
      using the novel "hybrid" algorithm, and compare them with patients with de novo
      CTOs. METHODS: We examined 521 consecutive patients who underwent CTO PCI at five
      high-volume PCI centers in the United States using the "hybrid" approach.
      Clinical, angiographic, and procedural outcomes were compared between CTOs due to
      ISR and de novo CTOs. RESULTS: The target CTO was due to ISR in 57 of 521
      patients (10.9%). Compared to patients with de novo CTOs, those with CTO due to
      ISR had higher frequency of diabetes (56.1% vs. 39.6%, P = 0.02) and less
      calcification (5.3% vs. 16.2%, P <0.001), but longer occlusion length [38 (29-55)
      vs. 30 (20-51), P = 0.04]. Technical success in the ISR and de novo group was
      89.4% and 92.5% (P = 0.43), respectively; procedural success was 86.0% and 90.3%
      (P = 0.31), respectively; and the incidence of major adverse cardiac events was
      3.5% and 2.2% (P = 0.63), respectively. CONCLUSIONS: Use of the "hybrid" approach
      to CTO PCI was associated with similarly high procedural success and similarly
      low major complication rates in patients with de novo and ISR CTOs.

PMID- 24585510
TI  - Evaluation of radiation dose to cardiac and pulmonary tissue among patients with
      stage IV Wilms tumor and pulmonary metastases.
AB  - BACKGROUND: Most patients with stage IV Wilms tumor (WT) and pulmonary metastases
      are treated with surgery, local radiotherapy (RT), and whole-lung irradiation
      (WLI). The Children's Oncology Group is studying whether WLI should only be given
      if metastatic lung lesions persist following induction chemotherapy. We
      hypothesized that radiation dose to cardiac and pulmonary organs are increased
      when WLI and abdominal RT fields are administered sequentially. PROCEDURE: We
      retrospectively identified 16 patients with stage IV WT and pulmonary metastases
      to model dosimetry plans for concurrent and sequential flank or whole abdomen and
      whole-lung fields. RESULTS: Treatment plans were evaluated for dosimetric
      endpoints to the heart and the lungs. The mean dose (Gy) was significantly higher
      to the heart (15.8 vs. 12.1, P < 0.0001) and lungs (14.1 vs. 12.2, P < 0.0002)
      when patients with stage IV WT and pulmonary metastases were treated with
      sequential RT. The percent tissue organ volumes (V) receiving high RT doses of 15
      and 20 Gy (V(15) and V(20)) were negligible in concurrent treatment plans.
      Comparatively, mean V(15) and V(20) values for sequential treatment plans were
      35% and 27%, respectively, for the heart, and 15% and 12%, for the lungs.
      CONCLUSIONS: The dose to the heart and lung tissue is significantly increased
      when WLI and abdominal RT fields are administered sequentially. While omission of
      WLI may be beneficial for patients achieving good response to induction
      chemotherapy, the less favorable response group may be subjected to increased
      risk of cardiac and pulmonary toxicities from sequential WLI.

PMID- 24585509
TI  - Peginterferon plus ribavirin versus interferon plus ribavirin for chronic
      hepatitis C.
AB  - BACKGROUND: Pegylated interferon (peginterferon) plus ribavirin is the
      recommended treatment for patients with chronic hepatitis C, but systematic
      assessment of the effect of this treatment compared with interferon plus
      ribavirin is needed. OBJECTIVES: To systematically evaluate the benefits and
      harms of peginterferon plus ribavirin versus interferon plus ribavirin for
      patients with chronic hepatitis C. SEARCH METHODS: We searched the Cochrane
      Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of
      Controlled Trials (CENTRAL), MEDLINE, EMBASE, Science Citation Index-Expanded,
      and LILACS. We also searched conference abstracts, journals, and grey literature.
      The last searches were conducted in September 2013. SELECTION CRITERIA: We
      included randomised clinical trials comparing peginterferon plus ribavirin versus
      interferon plus ribavirin with or without co-intervention(s) (e.g., other
      antiviral drugs) for chronic hepatitis C. Quasi-randomised and observational
      studies retrieved through the searches for randomised clinical trials were also
      considered for reports of harms. Our primary outcomes were liver-related
      morbidity, all-cause mortality, serious adverse events, adverse events leading to
      treatment discontinuation, other adverse events, and quality of life. Our
      secondary outcome was sustained virological response in serum, that is,
      undetectable hepatitis C virus RNA in serum by sensitive tests six months after
      the end of treatment. DATA COLLECTION AND ANALYSIS: Two review authors
      independently used a standardised data collection form. We meta-analysed data
      with both fixed-effect and random-effects models. For each outcome, we calculated
      the odds ratio (OR) (for liver-related morbidity or all-cause mortality) or the
      risk ratio (RR) along with 95% confidence interval (CI) based on intention-to
      treat analysis. We used domains of the trials to assess the risk of systematic
      errors (bias) and trial sequential analyses to assess the risk of random errors
      (play of chance).For each outcome, we calculated the RR with 95% CI based on
      intention-to-treat analysis. Effects of interventions on outcomes were assessed
      according to GRADE. MAIN RESULTS: We included 27 randomised trials with 5938
      participants. All trials had high risk of bias. We considered that the risk of
      bias did not impact on the quality of evidence for liver-related mortality and
      adverse event outcomes, but it did for virological response. All trials compared
      peginterferon alpha-2a or peginterferon alpha-2b plus ribavirin versus interferon
      plus ribavirin for participants with chronic hepatitis C. Three trials
      administered co-interventions (amantadine hydrochloride 200 mg daily to both
      intervention groups), and 24 trials were conducted without co-interventions. The
      effect observed between the two intervention groups regarding liver-related
      morbidity plus all-cause mortality (5/907 (0.55%) versus 4/882 (0.45%) was
      imprecise: OR 1.14 ( 95% CI 0.38 to 3.42; five trials; low quality of evidence),
      as was the risk of adverse events leading to treatment discontinuation (332/2692
      (12.3%) versus 409/2176 (18.8%); RR 0.86, 95% CI 0.68 to 1.09; 15 trials; low
      quality of evidence) or regarding adverse events leading to treatment
      discontinuation (332/2692 (12.3%) versus 409/2176 (18.8%); RR 0.86, 95% CI 0.66
      to 1.12; 17 trials; low quality of evidence). However, peginterferon plus
      ribavirin versus interferon plus ribavirin significantly increased the risk of
      neutropenia (332/2202 (15.1%) versus 117/1653 (7.1%); RR 2.15, 95% CI 1.76 to
      2.61; 13 trials), thrombocytopenia (65/1113 (5.8%) versus 23/1082 (2.1%); RR
      2.63, 95% CI 1.68 to 4.11; 10 trials), arthralgia (517/1740 (29.7%) versus
      282/1194 (23.6%); RR 1.19, 95% CI 1.05 to 1.35; four trials), injection site
      reaction (627/1168 (53.7%) versus 186/649 (28.7%); RR 1.71, 95% CI 1.50 to 1.93;
      four trials), and nausea (606/1784 (34.0%) versus 354/1239 (28.6%); RR 1.13, 95%
      CI 1.01 to 1.26; four trials). The most frequent adverse event was fatigue, which
      occurred in 57% of participants (2024/3608). No significant difference was noted
      between peginterferon plus ribavirin versus interferon plus ribavirin in terms of
      fatigue (1177/2062 (57.1%) versus 847/1546 (54.8%); RR 1.01, 95% CI 0.96 to 1.07;
      12 trials). No significant differences were reported between the two treatment
      groups regarding anaemia, headache, rigours, myalgia, pyrexia, weight loss,
      asthenia, depression, insomnia, irritability, alopecia, pruritus, skin rash,
      thyroid malfunction, decreased appetite, or diarrhoea. We were unable to identify
      any data on quality of life. Peginterferon plus ribavirin versus interferon plus
      ribavirin seemed to significantly increase the number of participants achieving
      sustained virological response (1673/3300 participants (50.7%) versus 1081/2804
      patients (36.7%); RR 1.39, 95% CI 1.25 to 1.56; I2 = 64%; 27 trials; very low
      quality of evidence). However, the risk of bias in the 13/27 (48.1%) trials
      reporting on this outcome was high and was considered only 'lower' in the
      remainder. Because the conventional meta-analysis did not reach its required
      information size (n = 14,486 participants), we used trial sequential analysis to
      control for risks of random errors. Again, in this analysis, the estimated effect
      was statistically significant in favour of peginterferon. Subgroup analyses
      according to risk of bias, viral genotype, baseline viral load, past treatment
      history, and type of intervention yielded similarly significant results favouring
      peginterferon over interferon on the outcome of sustained virological response.
      AUTHORS' CONCLUSIONS: Peginterferon plus ribavirin versus interferon plus
      ribavirin seems to significantly increase the proportion of patients with
      sustained virological response, as well as the risk of certain adverse events.
      However, we have insufficient evidence to recommend or reject peginterferon plus
      ribavirin for liver-related morbidity plus all-cause mortality compared with
      interferon plus ribavirin. The clinical consequences of achieved sustained
      virological response are unknown, as sustained virological response is still an
      unvalidated surrogate outcome. We found no evidence of the potential benefits on
      quality of life in patients with achieved sustained virological response. Further
      high-quality research is likely to have an important impact on our confidence in
      the estimate of patient-relevant outcomes and is likely to change our
      estimates.There is very low quality evidence that peginterferon plus ribavirin
      increases the proportion of patients with sustained virological response in
      comparison with interferon plus ribavirin. There is evidence that it also
      increases the risk of certain adverse events.

PMID- 24585511
TI  - Efficacy of high-intensity focused ultrasonography for noninvasive body sculpting
      in Chinese patients.
AB  - BACKGROUND AND OBJECTIVES: High-intensity focused ultrasound (HIFU) is a
      noninvasive technology for body contouring. HIFU is focused within the
      subcutaneous adipose tissue, causing coagulative necrosis and cell death. The
      objective of this study is to evaluate the effectiveness of a HIFU device for
      sculpting of the abdomen. MATERIALS AND METHODS: The system has a set focal depth
      of 1.3 cm. Twelve subjects with adipose thickness no less than 2.5 cm who met the
      screening criteria were recruited. Each subject received one treatment to the
      abdomen. The total fluence used per site was 150-165 J/cm(2) with a mean of 161
      J/cm(2) . The waist circumference at iliac crest and the point of maximum
      circumference were recorded at baseline, 4, 8, and 12 weeks post-treatment, as
      well as their weight and BMI. Subjects' rating on comfort level and satisfaction
      were collected via questionnaires at every follow-up. Standardized photographs
      were also taken with the Canfield System(r) at each visit. RESULTS: Seven out of
      12 subjects were satisfied with the outcome and 9 out of 12 would recommend this
      treatment to their friends and family. There was statistically significant
      improvement in the waist circumference measured at both the iliac crest (P-value
      0.013, 0.002, 0.005) and maximum waistline (P-value 0.003, 0.034, 0.023) at 4, 8,
      12 weeks post-treatment. Spearman's rho for correlation of energy level versus
      improvement showed that at 12 weeks post-treatment follow-up, the improvement
      significantly correlated with the total fluence per treatment (P-value 0.041).
      The higher the total fluence delivered, the larger the decrease in waist
      circumference. CONCLUSIONS: High-intensity focused ultrasound effectively
      decreases waist circumference in Chinese. The higher the total fluence delivered,
      the larger the decrease in waist circumference was observed.

PMID- 24585512
TI  - Reduction of voxel bleeding in highly accelerated parallel (1) H MRSI by direct
      control of the spatial response function.
AB  - PURPOSE: To substantially improve spatial localization in magnetic resonance
      spectroscopic imaging (MRSI) accelerated by parallel imaging. This is important
      in order to make MRSI more reliable as a tool for clinical applications. METHODS:
      The sensitivity encoding acceleration technique with spatial overdiscretization
      is applied for the reconstruction of parallel MRSI. In addition, the spatial
      response function is optimized by minimizing its deviation from a previously
      chosen target function. This modified minimum-norm sensitivity encoding-MRSI
      reconstruction approach is applied in this article for in vivo pulse-acquire MRSI
      of human brain at 7T with simulated acceleration factors of 2, 4, and 9 as well
      as actual 4-fold accelerated MRSI. RESULTS: The sidelobes of the spatial response
      function are significantly suppressed, which reduces far-reaching voxel bleeding.
      At the same time, the major enlargement of the effective voxel size, which would
      be introduced by conventional k-space apodization methods, is largely avoided.
      Regularization allows for a practical trade-off between noise minimization,
      effective voxel size, and unaliasing. Although not aiming at increasing the
      nominal spatial resolution, a better spatial specificity is achieved. CONCLUSION:
      Simultaneous suppression of short- and far-reaching voxel bleeding in MRSI is
      analyzed and reconstruction of highly accelerated parallel in vivo MRSI is
      demonstrated.

PMID- 24585514
TI  - Ten years of N-heteropentacenes as semiconductors for organic thin-film
      transistors.
AB  - Introducing N atoms to the pentacene backbone leads to N-heteropentacenes, whose
      properties can be tuned by changing the number, position and valence state of N
      atoms in the pentacene backbone. With a rapid development in recent years, N
      heteropentacenes and their derivatives have arisen as a new family of organic
      semiconductors with high performance in organic thin-film transistors (OTFTs).
      This article reviews the research efforts of developing N-heteropentacenes into
      organic semiconductors starting from 2003 with emphasis on the work of the
      author's group since 2009. The structure-property relationship and design
      rationale are highlighted based on an overview of reported organic semiconductors
      of N-heteropentacenes. 

PMID- 24585513
TI  - Second-trimester fetal aberrant right subclavian artery: original study,
      systematic review and meta-analysis of performance in detection of Down syndrome.
AB  - OBJECTIVES: First, to estimate the prevalence of fetal aberrant right subclavian
      artery (ARSA) in our population and its association with Down syndrome. Second,
      to determine the feasibility of ultrasound to visualize ARSA in the three planes.
      Finally, to carry out a systematic review of the literature on the performance of
      second-trimester ARSA to identify fetuses with Down syndrome. METHODS: ARSA was
      assessed by ultrasound in the axial plane and confirmed in the longitudinal and
      coronal planes during the second half of pregnancy in women attending our unit
      (from February 2011 to December 2012). A search of diagnostic tests for the
      assessment of ARSA was carried out in international databases. Relevant studies
      were subjected to a critical reading, and meta-analysis was performed with Meta
      DiSc. RESULTS: Of the 8781 fetuses in our population (mean gestational age: 24 +/
      5.4 weeks), 22 had Down syndrome. ARSA was detected in the axial view in 60
      cases (0.7%) and confirmed in the coronal view in 96.7% and in the longitudinal
      view in 6.7% (P < 0.001). Seven cases with ARSA had Down syndrome and all were in
      the non-isolated-ARSA group. The estimates of positive likelihood ratio (LR) were
      0 for isolated ARSA and 199 (95% CI, 88.9-445.2) for non-isolated ARSA. In the
      systematic review, six studies were selected for quantitative synthesis. The
      pooled estimates of positive and negative LRs for global ARSA were, respectively,
      35.3 (95% CI, 24.4-51.1) and 0.75 (95% CI, 0.64-0.87). For isolated ARSA, the
      positive and negative LRs were 0 (95% CI, 0.0-14.7) and 0.98 (95% CI, 0.94-1.02),
      respectively. CONCLUSIONS: The prevalence of ARSA seems close to 1%. The coronal
      plane is the most suitable for its confirmation after detection in the axial
      plane. Detection of isolated or non-isolated ARSA should guide decisions about
      karyotyping given that isolated ARSA shows a weak association with Down syndrome.

PMID- 24585519
TI  - Management of recurrent alveolar soft-part sarcoma of the tongue after external
      beam radiotherapy with iodine-125 seed brachytherapy.
AB  - BACKGROUND: Alveolar soft part sarcoma (ASPS) is a rare type of soft tissue
      sarcoma. The infrequency of ASPS is such that it accounts for <1% of all soft
      tissue sarcomas and <0.1% of sarcomas concerning the head and neck, primarily
      those involving the orbit (48%) and tongue (25%). Traditional chemotherapy or
      radiotherapy of ASPS is often associated with poor outcome, even after
      comprehensive interventions. METHODS AND RESULTS: We performed iodine-125 ((125)
      I) seed brachytherapy under ultrasound guidance through a submandibular puncture
      in a 4-year-old boy with recurrent ASPS of the tongue. The prescription dose was
      120 Gy; therefore, 35 (125) I seeds were implanted with 0.77 mCi per seed, the
      total amount of activity being 26.95 mCi. CT scans confirmed a complete response
      after the treatment. CONCLUSION: Our patient now has a recurrent-free survival of
      >30 months, an amount of time longer than the median rate described in the
      literature.

PMID- 24585515
TI  - Treatment of phenylketonuria using minicircle-based naked-DNA gene transfer to
      murine liver.
AB  - Host immune response to viral vectors, persistence of nonintegrating vectors, and
      sustained transgene expression are among the major challenges in gene therapy. To
      overcome these hurdles, we successfully used minicircle (MC) naked-DNA vectors
      devoid of any viral or bacterial sequences for the long-term treatment of murine
      phenylketonuria, a model for a genetic liver defect. MC-DNA vectors expressed the
      murine phenylalanine hydroxylase (Pah) complementary DNA (cDNA) from a liver
      specific promoter coupled to a de novo designed hepatocyte-specific regulatory
      element, designated P3, which is a cluster of evolutionary conserved
      transcription factor binding sites. MC-DNA vectors were subsequently delivered to
      the liver by a single hydrodynamic tail vein (HTV) injection. The MC-DNA vector
      normalized blood phenylalanine concomitant with reversion of hypopigmentation in
      a dose-dependent manner for more than 1 year, whereas the corresponding parental
      plasmid did not result in any phenylalanine clearance. MC vectors persisted in an
      episomal state in the liver consistent with sustained transgene expression and
      hepatic PAH enzyme activity without any apparent adverse effects. Moreover, 14
      20% of all hepatocytes expressed transgenic PAH, and the expression was observed
      exclusively in the liver and predominately around pericentral areas of the
      hepatic lobule, while there was no transgene expression in periportal areas.
      CONCLUSION: This study demonstrates that MC technology offers an improved safety
      profile and has the potential for the genetic treatment of liver diseases.

PMID- 24585520
TI  - Safety and long-term outcomes after percutaneous coronary intervention in
      patients with human immunodeficiency virus.
AB  - OBJECTIVE: This study aims to report the long-term outcomes after percutaneous
      coronary intervention (PCI) in human immunodeficiency virus (HIV+) patients.
      BACKGROUND: Sparse data exists regarding the risk of patients with HIV who
      undergo PCI. METHODS: Using a case-control design, we compared baseline
      characteristics, procedure-related outcomes, in-hospital, and 2-year clinical
      outcomes of 112 consecutive HIV+ patients versus 112 HIV- controls matched for
      age, gender, and diabetes mellitus who underwent PCI from April 2003 to September
      2011. RESULTS: Baseline characteristics were generally comparable, save for more
      African Americans and history of chronic renal insufficiency in the HIV+ vs. HIV-
      group (62.5% vs. 21.4%, P < 0.001) and (27.7% vs. 9.9%, P < 0.001). There was no
      correlation between CD4 nadir count and extent and diffuseness of coronary artery
      disease. The occurrence of major adverse cardiac events at 2 years was similar in
      both groups. Multivariable analysis for independent correlates of major adverse
      cardiac events at 2 years detected patients with a history of chronic renal
      insufficiency (OR: 2.44, 95% confidence interval: 1.02-5.83; P = 0.04) and acute
      myocardial infarction (OR: 2.92, 95% confidence interval: 1.39-6.15; P = 0.005)
      as correlates for outcome. Post-hoc analysis showed that drug-eluting stent (DES)
      use in the HIV+ group was beneficial. CONCLUSION: PCI in HIV+ patients is safe,
      with high procedural success rates, and produces similar outcomes to those seen
      in HIV- patients at 2 years. HIV+ patients should be treated with DES if
      possible.

PMID- 24585521
TI  - Liver transplant for congenital factor VII deficiency.
AB  - Congenital factor VII (FVII) deficiency is a rare, autosomal recessive bleeding
      disorder with a spectrum of phenotypes ranging from asymptomatic to life
      threatening intra-cranial hemorrhage (ICH). Orthotopic liver transplantation has
      been described for definitive treatment in a few patients with severe
      manifestations. We report a patient with congenital FVII deficiency and recurrent
      ICH, despite twice-weekly prophylaxis with recombinant activated FVII. At 17
      months of age, he underwent an orthotopic liver transplant. He is now 1-year post
      transplant, on maintenance immunosuppression with no hemorrhage or other
      complications.

PMID- 24585522
TI  - Whiplash: same elephant, different room.

PMID- 24585523
TI  - Chronic tophaceous gout.

PMID- 24585524
TI  - Reactive arthritis in ancient Egypt: a possible description in medical papyri.

PMID- 24585525
TI  - Restoration of overexpressed variable heavy chain 2 transcripts with tumor
      necrosis factor inhibitors in ankylosing spondylitis.

PMID- 24585526
TI  - Research priorities in gout: the patient perspective.

PMID- 24585527
TI  - Remission thresholds in spondyloarthritis: a prospective study in current
      practice.

PMID- 24585528
TI  - Occupational asbestos exposure and risk of esophageal, gastric and colorectal
      cancer in the prospective Netherlands Cohort Study.
AB  - The evidence for an association between occupational asbestos exposure and
      esophageal, gastric and colorectal cancer is limited. We studied this association
      specifically addressing risk differences between relatively low and high
      exposure, risk associated with cancer subtypes, the influence of potential
      confounders and the interaction between asbestos and smoking in relation to
      cancer risk. Using the Netherlands Cohort Study (n = 58,279 men, aged 55-69 years
      at baseline), asbestos exposure was estimated by linkage to a job-exposure
      matrix. After 17.3 years of follow-up, 187 esophageal, 486 gastric and 1,724
      colorectal cancer cases were available for analysis. The models adjusted for age
      and family history of cancer showed that mainly (prolonged) exposure to high
      levels of asbestos was statistically significantly associated with risk of
      esophageal adenocarcinoma (EAC), total and distal colon cancer and rectal cancer.
      For overall gastric cancer and gastric non-cardia adenocarcinoma (GNCA), also
      exposure to lower levels of asbestos was associated. Additional adjustment for
      lifestyle confounders, especially smoking status, yielded non-significant
      associations with overall gastric cancer and GNCA in the multivariable-adjusted
      model, except for the prolonged highly exposed subjects (tertile 3 vs. never: HR
      2.67, 95% CI: 1.11-6.44 and HR 3.35, 95% CI: 1.33-8.44, respectively). No
      statistically significant additive or multiplicative interaction between asbestos
      and smoking was observed for any of the studied cancers. This prospective
      population-based study showed that (prolonged) high asbestos exposure was
      associated with overall gastric cancer, EAC, GNCA, total and distal colon cancer
      and rectal cancer.

PMID- 24585529
TI  - Comment on "secondary bladder herniation in isolated gastroschisis justifies
      increased surveillance".

PMID- 24585530
TI  - Comment on "Doppler evaluation of the posterior cerebral artery in normally grown
      and growth restricted fetuses".

PMID- 24585531
TI  - Response to "Doppler evaluation of the posterior cerebral artery in normally
      grown and growth restricted fetuses".

PMID- 24585532
TI  - Characterization of nasal cavity-associated lymphoid tissue in ducks.
AB  - The nasal mucosa is involved in immune defense, as it is the first barrier for
      pathogens entering the body through the respiratory tract. The nasal cavity
      associated lymphoid tissue (NALT), which is found in the mucosa of the nasal
      cavity, is considered to be the main mucosal immune inductive site in the upper
      respiratory tract. NALT has been found in humans and many mammals, which
      contributes to local and systemic immune responses after intranasal vaccination.
      However, there are very few data on NALT in avian species, especially waterfowl.
      For this study, histological sections of the nasal cavities of Cherry Valley
      ducks were used to examine the anatomical location and histological
      characteristics of NALT. The results showed that several lymphoid aggregates are
      present in the ventral wall of the nasal cavity near the choanal cleft, whereas
      several more lymphoid aggregates were located on both sides of the nasal septum.
      In addition, randomly distributed intraepithelial lymphocytes and isolated
      lymphoid follicles were observed in the regio respiratoria of the nasal cavity.
      There were also a few lymphoid aggregates located in the lamina propria of the
      regio vestibularis, which was covered with a stratified squamous epithelium. This
      study focused on the anatomic and histological characteristics of the nasal
      cavity of the duck and performed a systemic overview of NALT. This will be
      beneficial for further understanding of immune mechanisms after nasal vaccination
      and the development of effective nasal vaccines for waterfowls.

PMID- 24585533
TI  - Detecting maternal-fetal genotype interactions associated with conotruncal heart
      defects: a haplotype-based analysis with penalized logistic regression.
AB  - Nonsyndromic congenital heart defects (CHDs) develop during embryogenesis as a
      result of a complex interplay between environmental exposures, genetics, and
      epigenetic causes. Genetic factors associated with CHDs may be attributed to
      either independent effects of maternal or fetal genes, or the intergenerational
      interactions between maternal and fetal genes. Detecting gene-by-gene
      interactions underlying complex diseases is a major challenge in genetic
      research. Detecting maternal-fetal genotype (MFG) interactions and
      differentiating them from the maternal/fetal main effects has presented
      additional statistical challenges due to correlations between maternal and fetal
      genomes. Traditionally, genetic variants are tested separately for maternal/fetal
      main effects and MFG interactions on a single-locus basis. We conducted a
      haplotype-based analysis with a penalized logistic regression framework to
      dissect the genetic effect associated with the development of nonsyndromic
      conotruncal heart defects (CTD). Our method allows simultaneous model selection
      and effect estimation, providing a unified framework to differentiate
      maternal/fetal main effect from the MFG interaction effect. In addition, the
      method is able to test multiple highly linked SNPs simultaneously with a
      configuration of haplotypes, which reduces the data dimensionality and the burden
      of multiple testing. By analyzing a dataset from the National Birth Defects
      Prevention Study (NBDPS), we identified seven genes (GSTA1, SOD2, MTRR, AHCYL2,
      GCLC, GSTM3, and RFC1) associated with the development of CTDs. Our findings
      suggest that MFG interactions between haplotypes in three of seven genes, GCLC,
      GSTM3, and RFC1, are associated with nonsyndromic conotruncal heart defects. 

PMID- 24585534
TI  - Temporal lobe dysplasia: a characteristic sonographic finding in thanatophoric
      dysplasia.
AB  - OBJECTIVE: To determine the incidence of temporal lobe dysplasia (TLD) detected
      on prenatal ultrasound in thanatophoric dysplasia (TD) over an 11-year period in
      a tertiary referral center. METHODS: An 11-year retrospective review of perinatal
      autopsies from 2002 to 2013 was performed to identify cases of TD. The ultrasound
      images and corresponding reports of all TD cases were examined for the presence
      of TLD. The same set of images subsequently underwent a retrospective review by a
      perinatal radiologist with knowledge of the features of TLD to determine whether
      they could be identified. RESULTS: Thirty-one cases of TD underwent perinatal
      autopsy, and prenatal ultrasound imaging was available for review in 24 (77%).
      Mean gestational age at diagnosis of TD was 21.3 (range, 18-36) weeks. TLD was
      identified and reported in 6/24 (25%) cases; all six cases occurred after 2007.
      Retrospective interpretation of the ultrasound images identified features of TLD
      in 10 additional cases. In total, 16/24 (67%) cases displayed sonographic
      evidence of TLD. Temporal trends showed that TLD features were present in 50%
      (5/10) of all TD cases between 2002 and 2006 and in 79% (11/14) of those detected
      between 2007 and 2013. CONCLUSIONS: At present, the detection rate of TLD by
      ultrasound is low but may be increased by modified brain images that enhance
      visualization of the temporal lobes. Prenatal identification of TLD may help in
      the prenatal diagnosis of TD and thus provide more accurate prenatal counseling
      and guide molecular investigations to confirm the specific diagnosis of TD.

PMID- 24585535
TI  - Patient Health Questionnaire-2 as a screening tool for psychological distress in
      brain tumor patients.

PMID- 24585536
TI  - Authors' response: Patient Health Questionnaire-2 as a screening tool for
      psychological distress in brain tumor patients.

PMID- 24585539
TI  - Reply: To PMID 22095893.

PMID- 24585540
TI  - Standardizing radiation dose reporting in the pediatric cardiac catheterization
      laboratory-a multicenter study by the CCISC (Congenital Cardiovascular
      Interventional Study Consortium).
AB  - OBJECTIVES: We examine normalized air Kerma area product (PKA ) by body weight
      (PKA /BW) as a reference value of radiation dose and benchmark PKA /BW in
      pediatric laboratories using a multicenter registry database. BACKGROUND:
      Reduction of radiation dose is an important quality improvement task in pediatric
      cardiac catheterization laboratories. Physicians need to agree on a standard
      method of reporting radiation dose that would allow comparisons to be made
      between operators and institutions. METHODS: This was a multicenter observational
      study of radiation dose in pediatric laboratories. Patient demographic,
      procedural and radiation data including fluoroscopic time and PKA (uGy m(2) )
      were analyzed. PKA /BW was obtained by indexing PKA to body weight. RESULTS: A
      total of 8,267 pediatric catheterization procedures (age <18 years) were included
      from 16 institutions. The procedures consisted of diagnostic (n = 2,827),
      transplant right ventricular (RV) biopsy (n = 1,172), and interventional
      catheterizations (n = 4268). PKA correlated with body weight better than with age
      and best correlated with weight-fluoroscopic time product. PKA /BW showed
      consistent values across pediatric ages. Interventional catheterizations had the
      highest PKA /BW (50th, 75th, and 90th percentiles: 72, 151, and 281 MUGy m(2)
      /kg), followed by diagnostic (59, 105, and 175 MUGy m(2) /kg) and transplant RV
      biopsy (27, 79, and 114 MUGy m(2) /kg). CONCLUSION: PKA /BW appeared to be the
      most reliable standard to report radiation dose across all procedure types and
      patient age. We recommend PKA /BW to be used as the standard unit in documenting
      radiation usage in pediatric laboratories and can be used to evaluate strategies
      to lower radiation dosage in pediatric patients undergoing cardiac
      catheterizations. (c) 2014 Wiley Periodicals, Inc.

PMID- 24585543
TI  - Acetylcholine-triggered cargo release from supramolecular nanovalves based on
      different macrocyclic receptors.
AB  - Acetylcholine (ACh), a neurotransmitter located in cholinergic synapses, can
      trigger cargo release from mesoporous silica nanoparticles equipped with
      calixarene- or pillarene-based nanovalves by removing macrocycles from the stalk
      components. The amount and speed of cargo release can be controlled by varying
      the concentration of ACh in solution or changing the type of gating macrocycle.
      Although this proof-of-concept study is far from a real-life application, it
      provides a possible route to treat diseases related to the central nervous
      system. 

PMID- 24585544
TI  - Secreted semaphorin 5A activates immune effector cells and is a biomarker for
      rheumatoid arthritis.
AB  - OBJECTIVE: To investigate the role of the multifunctional protein semaphorin 5A
      (Sema5A) in modulating cellular immune responses and as a biomarker in rheumatoid
      arthritis (RA). METHODS: A soluble form of recombinant Sema5A was used to assess
      its effect on the functions of primary T cells and natural killer (NK) cells
      isolated from the peripheral blood of healthy donors. Cell proliferation and
      expression of transcription factors were determined by flow cytometry. Cytokine
      secretion was analyzed using Luminex technology. Serum samples obtained from 145
      patients with RA and control serum samples obtained from healthy individuals or
      patients with non-RA rheumatic diseases were analyzed for the presence of
      secreted Sema5A, using enzyme-linked immunosorbent assays and immunoblotting.
      RESULTS: Soluble Sema5A strongly increased T cell and NK cell proliferation and
      induced the secretion of proinflammatory Th1/Th17 cytokines. Accordingly, Sema5A
      stimulation caused significant up-regulation of T-bet and retinoic acid receptor
      related orphan nuclear receptor gammat levels in T cells. In addition,
      significantly elevated levels of secreted Sema5A were detected in the serum of
      patients with RA compared with control serum. Sema5A levels were highest in
      patients with RA who were positive for the RA biomarker anti-cyclic citrullinated
      peptide (P < 0.001 versus patients with systemic lupus erythematosus and patients
      with Sjogren's syndrome) and correlated with the levels of rheumatoid factor.
      CONCLUSION: Soluble Sema5A is a potent activator of T cells and NK cells in
      vitro, and high serum levels of Sema5A are associated with RA. Taken together,
      the results indicate that Sema5A contributes to the pathogenesis of RA through
      antigen-independent T cell and NK cell activation. Hence, Sema5A is a promising
      complementary biomarker for the diagnosis of RA.

PMID- 24585545
TI  - Complex IGH rearrangements in multiple myeloma: Frequent detection discrepancies
      among three different probe sets.
AB  - Primary IGH translocations involving seven recurrent partner loci and oncogenes
      are present in about 40% of multiple myeloma tumors. Secondary IGH
      rearrangements, which occur in a smaller fraction of tumors, usually are complex
      structures, including insertions or translocations that can involve three
      chromosomes, and often with involvement of MYC. The main approach to detect IGH
      rearrangements is interphase-but sometimes metaphase-FISH strategies that use a
      telomeric variable region probe and a centromeric constant region/ Ealpha
      enhancer or 3' flanking probe to detect a separation of these two probes, or a
      fusion of these probes with probes located at nonrandom partner sites in the
      genome. We analyzed 18 myeloma cell lines for detection discrepancies among
      Vysis, Cytocell, and in-house IGH probe sets that hybridize with differing
      sequences in the IGH locus. There were no detection discrepancies for the three
      telomeric IGH probes, or for unrearranged IGH loci or primary IGH translocations
      using the centromeric IGH probes. However, the majority of complex IGH
      rearrangements had detection discrepancies among the three centromeric IGH
      probes.

PMID- 24585546
TI  - Bone mineral density among long-term survivors of childhood acute lymphoblastic
      leukemia: results from the St. Jude Lifetime Cohort Study.
AB  - BACKGROUND: The prevalence of low bone mineral density (BMD) in adult survivors
      of childhood acute lymphoblastic leukemia (ALL), and the degree of recovery or
      decline, are not well elucidated. PROCEDURE: Study subjects (age >= 18 years and
      >=10 years post-diagnosis) participated in an institutional follow-up protocol
      and risk-based clinical evaluation based on Children's Oncology Group guidelines.
      Trabecular volumetric BMD was ascertained using quantitative computed tomography,
      reported as age- and sex-specific Z-scores. RESULTS: At median age 31 years, 5.7%
      of 845 subjects had a BMD Z-score of <=-2 and 23.8% had a Z-score of -1 to -2.
      Cranial radiation dose of >=24 Gy, but not cumulative methotrexate or prednisone
      equivalence doses, was associated with a twofold elevated risk of a BMD Z-score
      of <=-1. The cranial radiation effect was stronger in females than in males. In a
      subset of 400 subjects, 67% of those who previously had a BMD Z-score of <=-2
      improved by one or more categories a median of 8.5 years later. CONCLUSIONS: Very
      low BMD was relatively uncommon in this sample of adult survivors of childhood
      ALL, and BMD Z-scores tended to improve from adolescence to young adulthood. High
      dose cranial or craniospinal radiation exposure was the primary predictor of
      suboptimal BMD in our study. Given that cranial radiation treatment for childhood
      ALL is used far more sparingly now than in earlier treatment eras, concerns about
      persistently low BMD among most current childhood ALL patients may be
      unwarranted.

PMID- 24585547
TI  - Overexpression of ZFX confers self-renewal and chemoresistance properties in
      hepatocellular carcinoma.
AB  - Zinc finger protein X-linked (ZFX) is a zinc finger protein of Zfy family, which
      is highly conserved in vertebrates. This transcriptional regulator is not only
      highly expressed in embryonic stem cells (ESC) and hematopoietic stem cells, but
      is also upregulated in a number of human cancers where it is functional related
      to cell proliferation and survival. Hepatocellular carcinoma (HCC) is highly
      aggressive cancer that commonly resistant to most chemotherapies and displays
      stemness characteristics. In this study, we examined the expression of ZFX in HCC
      and its possible functional implications in liver tumorigenesis. Quantitative RT
      PCR analysis showed common overexpressions of ZFX in 51.8% HCC tumors when
      compared with their adjacent nonmalignant liver (n = 43/83; p = 0.004). Inline
      with the pluripotency role of ZFX, we found silencing of ZFX readily inhibited
      self-renewal capability (p = 0.0022), colony formation ability (p < 0.0001) and
      cell proliferation (p < 0.0001) through G0/G1 cell cycle arrest of HCC cells (p =
      0.0038). In addition, suppression of ZFX sensitized HCC cells to chemotherapeutic
      agent cisplatin (p < 0.0001). Further investigations suggested that ZFX bind on
      the promoter of two important mediators, namely Nanog and SOX-2, activating their
      expressions in HCC (p < 0.0001). Moreover, in vivo xenograft study demonstrated
      that overexpression of ZFX would promote the tumor growth (p = 0.031). Taken
      together, our results show, for the first time, commonly overexpressions of ZFX
      in HCC, where it likely contributes to the stemness and pluripotent behavior of
      this highly malignant cancer. 

PMID- 24585549
TI  - Craniofacial shape variation in Twist1+/- mutant mice.
AB  - Craniosynostosis (CS) is a relatively common birth defect resulting from the
      premature fusion of one or more cranial sutures. Human genetic studies have
      identified several genes in association with CS. One such gene that has been
      implicated in both syndromic (Saethre-Chotzen syndrome) and nonsyndromic forms of
      CS in humans is TWIST1. In this study, a heterozygous Twist1 knock out (Twist1(+/
      ) ) mouse model was used to study the craniofacial shape changes associated with
      the partial loss of function. A geometric morphometric approach was used to
      analyze landmark data derived from microcomputed tomography scans to compare
      craniofacial shape between 17 Twist1(+/-) mice and 26 of their Twist1(+/+) (wild
      type) littermate controls at 15 days of age. The results show that despite the
      purported wide variation in synostotic severity, Twist1(+/-) mice have a
      consistent pattern of craniofacial dysmorphology affecting all major regions of
      the skull. Similar to Saethre-Chotzen, the calvarium is acrocephalic and wide
      with an overall brachycephalic shape. Mutant mice also exhibited a shortened
      cranial base and a wider and shorted face, consistent with coronal CS associated
      phenotypes. The results suggest that these differences are at least partially the
      direct result of the Twist1 haploinsufficiency on the developing craniofacial
      skeleton. This study provides a quantitative phenotype complement to the
      developmental and molecular genetic research previously done on Twist1. These
      results can be used to generate further hypotheses about the effect of Twist1 and
      premature suture fusion on the entire craniofacial skeleton.

PMID- 24585548
TI  - Long-term epigenetic effects of exposure to low doses of 56Fe in the mouse lung.
AB  - Despite significant progress, the long-term health effects of exposure to high
      charge (Z) and energy (E) nuclei (HZEs) and the underlying mechanisms remain
      poorly understood. Mouse studies show that space missions can result in pulmonary
      pathological states. The goal of this study was to evaluate the pro-fibrotic and
      pro-carcinogenic effects of exposure to low doses of heavy iron ions ((56)Fe) in
      the mouse lung. Exposure to (56)Fe (600 MeV; 0.1, 0.2 and 0.4 Gy) resulted in
      minor pro-fibrotic changes, detected at the beginning of the fibrotic phase (22
      weeks post exposure), which were exhibited as increased expression of chemokine
      Ccl3, and interleukin Il4. Epigenetic alterations were exhibited as global DNA
      hypermethylation, observed after exposure to 0.4 Gy. Cadm1, Cdh13, Cdkn1c, Mthfr
      and Sfrp1 were significantly hypermethylated after exposure to 0.1 Gy, while
      exposure to higher doses resulted in hypermethylation of Cdkn1c only. However,
      expression of these genes was not affected by any dose. Congruently with the
      observed patterns of global DNA methylation, DNA repetitive elements were
      hypermethylated after exposure to 0.4 Gy, with minor changes observed after
      exposure to lower doses. Importantly, hypermethylation of repetitive elements
      coincided with their transcriptional repression. The findings of this study will
      aid in understanding molecular determinants of pathological states associated
      with exposure to (56)Fe, as well as serve as robust biomarkers for the delayed
      effects of irradiation. Further studies are clearly needed to investigate the
      persistence and outcomes of molecular alterations long term after exposure.

PMID- 24585551
TI  - Rhythm course over 5 years following surgical ablation for atrial fibrillation.
AB  - OBJECTIVES: Reporting methods for surgical ablation (SA) of atrial fibrillation
      (AF) were standardized by the Heart Rhythm Society Guidelines, stating that
      results should be reported only for the first 2 years following SA. The purpose
      of this study was to assess the outcome of SA over 5 years and determine
      predictors for success over that period. METHODS: Data were collected
      prospectively for all SA (n=787). Rhythm was verified by electrocardiogram and
      Holter monitoring at 3, 6, 9, 12, 18 and 24 months and yearly thereafter.
      Patients with rhythm status available at 2 and 5 years were included in the main
      analyses (n=137). Multivariate logistic regression was used for predictors of
      normal sinus rhythm (NSR). Receiver operating curves compared 2- and 5-year
      predicted probability against observed rhythm status by year. RESULTS: Return to
      NSR at 2 years was 88% (80% off antiarrhythmic drugs) and at 5 years was 85% (71%
      off antiarrhythmic drugs). The majority of patients (64%) had stable NSR over 5
      years. The only predictor for 2-year NSR was smaller left atrial size (odds ratio
      [OR]=0.40, P=0.044). Predictors for 5-year NSR were smaller left atrial size
      (OR=0.28, P=0.002), age (OR=0.91, P=0.031) and length of hospital stay (OR=0.85,
      P=0.026). CONCLUSIONS: This study demonstrated stable results of SA for AF over
      time with somewhat different predictors for 2- and 5-year NSR in a group of
      patients with complete follow-up at both time points. Accurate models to
      determine predictors for success of SA more than 2 years after surgery are
      essential to better understand long-term outcome for patients with AF.

PMID- 24585550
TI  - Non-intubated thoracoscopic surgery using internal intercostal nerve block, vagal
      block and targeted sedation.
AB  - OBJECTIVES: Thoracoscopic surgery using internal intercostal nerve block, vagal
      block and targeted sedation without endotracheal intubation is a promising
      technique for selected patients, but little is known about its feasibility and
      safety. METHODS: We evaluated 109 patients with lung (105), mediastinal (3) or
      pleural (1) tumours treated using non-intubated thoracoscopic surgery. Internal,
      intercostal nerve block was performed at the T3-T8 intercostal level and vagal
      block was performed adjacent to the vagus nerve at the level of the lower trachea
      for right-sided operations and at the level of the aortopulmonary window for left
      sided operations. Sedation was performed with propofol infusion to achieve a
      bispectral index value between 40 and 60. RESULTS: Thoracoscopic lobectomy was
      performed in 43 patients, wedge resection in 50, segmentectomy in 12 and
      mediastinal or pleural tumour excision in 4. Three patients (2.8%) required
      conversion to intubated one-lung ventilation because of vigorous mediastinal
      movement and dense diaphragmatic adhesions. Anaesthetic induction and operation
      had a median duration of 10.0 and 127.0 min, respectively. Operative
      complications developed in 13 patients with air leaks for more than 3 days and 1
      patient required transfusion of blood products. The median postoperative chest
      drainage and hospital stay were 2.0 and 4.0 days, respectively. CONCLUSIONS: Non
      intubated thoracoscopic surgery using internal intercostal nerve block, vagal
      block and targeted sedation is technically feasible and safe in surgical
      treatment of lung, mediastinal and pleural tumours in selected patients.

PMID- 24585552
TI  - Contrast echocardiography: a novel technique for assessment of total aortic
      regurgitation following transapical aortic valve implantation.
AB  - OBJECTIVES: Aortic regurgitation (AR) is a possible complication following
      transcatheter aortic valve implantation (TAVI) which is associated with less
      favourable outcomes. Quantification of total regurgitation caused by multiple,
      multidirectional jets remains controversial. The purpose of this study was to
      assess the usefulness of retrograde contrast echocardiography in quantification
      of total AR following TAVI and to evaluate its prognostic significance. METHODS:
      In 245 patients following Edwards Sapien valve (Edwards Lifesciences, Irvine, CA,
      USA) implantation, we performed retrograde contrast transoesophageal
      echocardiography to quantify AR immediately after TAVI. The contrast (20 ml
      agitated gelatine polysuccinate, Gelafundin 4%, Braun, Melsungen, Germany) was
      injected as a bolus into the sinotubular junction of the aorta through a pigtail
      catheter. We measured the area of the regurgitant cloud during mid- to end
      diastole. A regurgitant area of >=3.8 cm2 was determined as an indicator of
      relevant AR. Sensitivity of this was compared through angiography and Doppler
      echocardiography. To assess whether AR identified by this novel method
      independently determined survival, a multivariate model was applied. RESULTS:
      Angiography, Doppler echocardiography and contrast echocardiography recognized
      15, 23 and 56 patients with relevant regurgitation. Multivariate analysis
      including a regurgitant area of >=3.8 cm2, New York Heart Association (NYHA)
      class IV, age and creatinine concentration identified a regurgitant area of >=3.8
      cm2 (P=0.027) as independent risk factor for 2-year survival. CONCLUSIONS:
      Contrast echocardiography is a simple method for quantification of total AR
      following TAVI and is more sensitive than angiography or Doppler
      echocardiography. Its clinical relevance is demonstrated by the impact of the AR
      detected by contrast echocardiography on survival.

PMID- 24585553
TI  - Aortic arch surgery in octogenarians: is it justified?
AB  - OBJECTIVES: Elderly patients are sometimes denied aortic arch surgery because of
      the perception of poor outcomes and an unacceptable quality of life (QOL). In
      this study, we evaluated the early clinical outcomes, long-term survival and QOL
      following surgical treatment for aortic arch disease in octogenarian patients.
      METHODS: A total of 47 consecutive patients over the age of 80 years were
      referred to our institutions. Of these patients, 20 underwent surgical
      intervention (surgical group) and 27 were treated medically (medical group).
      Kaplan-Meier survival analysis was performed between the two groups, and the
      results were compared with age-matched population data. The risk factors for
      mortality were determined using a Cox regression analysis. A QOL assessment was
      performed using the 36-item Short Form Health Survey. RESULTS: The patient
      characteristics at baseline were not significantly different between the two
      groups. In the surgical cases, conventional total aortic arch replacement was
      performed in 15 patients, debranched thoracic endovascular aortic repair (TEVAR)
      in 2 and chimney TEVAR in 3. Emergency procedures were performed in 3 patients.
      No hospital deaths occurred in the surgical groups. Reoperation for bleeding was
      required in 2 patients, and prolonged mechanical ventilation was required in 4
      patients. The 5-year survival was 61.5% in the surgical group and 14.2% in the
      medical group (P = 0.02). Freedom from aorta-related death at 5 years was 92.3%
      in the surgical group and 32.3% in the medical group (P = 0.01). There were no
      differences in the 5-year survival between patients undergoing surgical
      intervention and the sex- and age-matched population (P = 0.80), whereas the 5
      year survival was significantly lower in patients who received medical therapy
      relative to the sex- and age-matched population (P < 0.001). Medical therapy was
      the sole risk factor for mortality (hazard ratio: 3.16, P = 0.04). Among the
      survivors at mid-term, the quality-of-life measures were similar between those in
      the surgical group and those in the medical group. CONCLUSIONS: Surgical
      intervention for aortic arch disease in octogenarians can yield satisfactory
      early clinical outcomes and acceptable mid-term survival with adequate daily
      activity. This study indicates that among octogenarians, age alone should not
      disqualify a patient from receiving an aortic arch intervention.

PMID- 24585554
TI  - Saline-cooled radiofrequency coagulation during thoracoscopic surgery for giant
      bulla.
AB  - Two patients were admitted to our hospital due to giant bullae. During
      thoracoscopic surgery, saline-cooled radiofrequency coagulation devices were used
      to shrink the wall of the bulla. In each case, the volume of the bulla was
      gradually reduced and the boundary between the lung and bulla was clearly
      delineated. This method is considered to be useful for performing thoracoscopic
      surgery of giant bulla. 

PMID- 24585555
TI  - First-trimester maternal ophthalmic artery Doppler analysis for prediction of pre
      eclampsia.
AB  - OBJECTIVE: To determine the performance of a multiparametric test comprising
      maternal risk factors, uterine artery Doppler and ophthalmic artery Doppler in
      the first trimester of pregnancy for the prediction of pre-eclampsia (PE).
      METHODS: This prospective observational cohort study recruited patients in the
      first trimester of pregnancy. Maternal uterine artery and ophthalmic artery
      Doppler assessments were performed in 440 singleton pregnancies at 11-14 weeks of
      gestation. Additional history was obtained through participant questionnaires,
      and follow-up occurred to discharge postdelivery. The normotensive and pre
      eclamptic groups were compared using parametric (Student's t-test) and non
      parametric (Mann-Whitney U-test) tests. Univariable and multivariable logistic
      regression analyses were performed to determine which biophysical factors, and
      which of the factors among the maternal characteristics and medical and obstetric
      history, had a significant contribution to the prediction of PE in a
      multiparametric model. RESULTS: Thirty-one (7%) patients developed PE, including
      nine (2%) who required delivery before 34 weeks (early PE) and 22 (5%) with late
      PE. There were statistically significant differences in uterine artery
      pulsatility index (UtA-PI) and ophthalmic artery first diastolic peak (PD1) mean
      values between the PE and control groups. In a multiparametric model, both UtA-PI
      and PD1 achieved a 67% detection rate for early PE, although when combined, the
      detection rate only increased to 68%. CONCLUSIONS: The efficiency of ophthalmic
      artery PD1 in the first trimester as a predictive marker for the later
      development of PE was approximately equal to that described for uterine artery
      Doppler. Although these findings do not support the replacement of uterine artery
      Doppler analysis in multiparametric predictive models for PE, they do provide
      novel insights into first-trimester maternal systemic vascular changes that
      precede the clinical development of this condition.

PMID- 24585556
TI  - Chemiluminometric determination of ascorbic acid in pharmaceutical formulations
      exploiting photo-activation of GSH-capped CdTe quantum dots.
AB  - An automated multi-pumping flow system is proposed for the chemiluminometric
      determination of ascorbic acid in pharmaceutical formulations, relying on the
      ability of semiconductor nanocrystals to generate short-lived reactive species
      upon photo-irradiation. A photo-unit based on visible-light-emitting diodes is
      used to photo-excite cadmium telluride (CdTe) quantum dots capped with
      glutathione, leading to the generation of radicals that react with luminol under
      alkaline conditions, yielding the chemiluminescence. Ascorbic acid acts as a
      radical scavenger, preventing the oxidation of luminol, thus ensuring a
      concentration-dependent chemiluminescence quenching. After system optimization, a
      linear working range of 5.0 * 10(-7) to 5.0 * 10(-6) mol/L ascorbic acid (r =
      0.9967, n = 5) was attained, with a detection limit of 3.05 * 10(-7) mol/L and a
      sampling rate of 200/h. The flow system was applied to the analysis of
      pharmaceutical formulations and the results were in good agreement with those
      obtained by the reference titrimetric procedure (RD < +/- 4.3%, n = 7).

PMID- 24585557
TI  - Beyond tumor necrosis factor inhibition: the expanding pipeline of biologic
      therapies for inflammatory diseases and their associated infectious sequelae.
AB  - Patients with rheumatoid arthritis and other immune-mediated inflammatory
      diseases are at higher risk for infectious morbidity and mortality, partially due
      to the therapies used to treat these conditions. Both prednisone and targeted
      biologic therapies such as tumor necrosis factor antagonists have been implicated
      to various degrees, although in some cases firm data are lacking with regard to
      certain types of infections. To date, there is a paucity of information regarding
      the infectious risks associated with the newer biologic agents. As new biologic
      agents become available for use, their potential infectious risks will challenge
      infectious disease clinicians who must work to prevent, diagnose, and treat
      infections in this setting. This article reviews our current understanding of
      infectious risk in the setting of targeted therapies and provides an update of
      the immune system targets and potential infectious sequelae of both current and
      emerging biologic therapies. 

PMID- 24585559
TI  - Performance of QuantiFERON-TB Gold and tuberculin skin test relative to subjects'
      risk of exposure to tuberculosis.
AB  - BACKGROUND: Performance of QuantiFERON-TB Gold In-Tube (QFT-GIT) and tuberculin
      skin test (TST) has not been compared in a US college population with varying
      risk of tuberculosis exposure. METHODS: We performed a retrospective chart review
      of students tested for tuberculosis at the University of Pennsylvania Student
      Health Service between 2009 and 2011. We stratified students into high-, low-,
      and no-risk categories for exposure to tuberculosis and compared QFT-GIT and TST
      performance in risk groups adjusting demographic characteristics. RESULTS: During
      the study period, 15 936 tuberculosis tests were performed in 9483 college
      students. Coming from a tuberculosis-endemic country was the only risk factor
      significantly associated with having a positive result (odds ratio [OR] 12.9; 95%
      confidence interval [CI], 10.2-16.5). Test specificity was higher for TST than
      QFT-GIT (99.7% vs 91.4%; P < .0001). Application of a higher threshold for
      positivity improved comparability of QFT-GIT with TST in the low-risk group
      (adjusted OR [AOR] 1.2; 95% CI, .4-3.3) but not in the high-risk group (AOR .4;
      95% CI, .3-.5). CONCLUSIONS: QFT-GIT was less specific than TST. Our findings
      support the use of TST for US college students who need tuberculosis testing and
      the use of risk-stratified interpretation for students who are tested with QFT
      GIT.

PMID- 24585558
TI  - Effect of baseline renal function on tenofovir-containing antiretroviral therapy
      outcomes in Zambia.
AB  - BACKGROUND: Although tenofovir disoproxil fumarate (TDF) use has increased as
      part of first-line antiretroviral therapy (ART) across sub-Saharan Africa, renal
      outcomes among patients receiving TDF remain poorly understood. We assessed
      changes in renal function and mortality in patients starting TDF- or non-TDF
      containing ART in Lusaka, Zambia. METHODS: We included patients aged >=16 years
      who started ART from 2007 onward, with documented baseline weight and serum
      creatinine. Renal dysfunction was categorized as mild (estimated glomerular
      filtration rate [eGFR], 60-89 mL/min), moderate (30-59 mL/min), or severe (<30
      mL/min) according to the chronic kidney disease-epidemiology (CKD-EPI) formula.
      Differences in eGFR during ART were analyzed using linear mixed-effect models.
      The odds of developing moderate or severe eGFR decrease and mortality were
      assessed using logistic and competing risk regression, respectively. RESULTS: We
      included 62 230 adults, of which 38 716 (62.2%) initiated a TDF-based regimen.
      The proportion with moderate or severe renal dysfunction at baseline was lower in
      the TDF than in the non-TDF group (1.9% vs 4.0%). Among patients with no or mild
      renal dysfunction, those receiving TDF were more likely to develop moderate
      (adjusted odds ratio, 3.11; 95% confidence interval, 2.52-3.87) or severe (2.43;
      1.80-3.28) eGFR decrease, although the incidence in such episodes was low. Among
      patients with moderate or severe renal dysfunction at baseline, renal function
      improved independently of ART regimen, and mortality rates were similar in both
      treatment groups. CONCLUSIONS: TDF use did not attenuate renal function recovery
      or increase the mortality rate in patients with renal dysfunction. Further
      studies are needed to determine the role of routine renal function monitoring
      before and during ART use in Africa.

PMID- 24585560
TI  - Editorial commentary: Risks and benefits of tenofovir in the context of kidney
      dysfunction in sub-Saharan Africa.

PMID- 24585561
TI  - The state of norovirus vaccines.
AB  - Noroviruses represent the most important cause of acute gastroenteritis
      worldwide; however, currently no licensed vaccine exists. Widespread vaccination
      that minimizes overall norovirus disease burden would benefit the entire
      population, but targeted vaccination of specific populations such as healthcare
      workers may further mitigate the risk of severe disease and death in vulnerable
      populations. While a few obstacles hinder the rapid development of efficacious
      vaccines, human trials for virus-like particle (VLP)-based vaccines show promise
      in both immune response and protection studies, with availability of vaccines
      being targeted over the next 5-10 years. Ongoing work including identification of
      important norovirus capsid antigenic sites, development of improved model
      systems, and continued studies in humans will allow improvement of future
      vaccines. In the meantime, a better understanding of norovirus disease course and
      transmission patterns can aid healthcare workers as they take steps to protect
      high-risk populations such as the elderly and immunocompromised individuals from
      chronic and severe disease.

PMID- 24585563
TI  - Editorial commentary: monitoring early warning indicators for HIV drug resistance
      in South Africa: challenges and opportunities.

PMID- 24585562
TI  - Outbreak of measles among persons with prior evidence of immunity, New York City,
      2011.
AB  - BACKGROUND: Measles was eliminated in the United States through high vaccination
      coverage and a public health system able to rapidly respond to measles. Measles
      may occur among vaccinated individuals, but secondary transmission from such
      individuals has not been documented. METHODS: Suspected patients and contacts
      exposed during a measles outbreak in New York City in 2011 were investigated.
      Medical histories and immunization records were obtained. Cases were confirmed by
      detection of measles-specific immunoglobulin M and/or RNA. Tests for measles
      immunoglobulin G (IgG), IgG avidity, measurement of measles neutralizing antibody
      titers, and genotyping were performed to characterize the cases. RESULTS: The
      index patient had 2 doses of measles-containing vaccine; of 88 contacts, 4
      secondary patients were confirmed who had either 2 doses of measles-containing
      vaccine or a past positive measles IgG antibody. All patients had laboratory
      confirmation of measles infection, clinical symptoms consistent with measles, and
      high-avidity IgG antibody characteristic of a secondary immune response.
      Neutralizing antibody titers of secondary patients reached >80 000 mIU/mL 3-4
      days after rash onset and that of the index was <500 mIU/mL 9 days after rash
      onset. No additional cases of measles occurred among 231 contacts of secondary
      patients. CONCLUSIONS: This is the first report of measles transmission from a
      twice-vaccinated individual with documented secondary vaccine failure. The
      clinical presentation and laboratory data of the index patient were typical of
      measles in a naive individual. Secondary patients had robust anamnestic antibody
      responses. No tertiary cases occurred despite numerous contacts. This outbreak
      underscores the need for thorough epidemiologic and laboratory investigation of
      suspected cases of measles regardless of vaccination status.

PMID- 24585564
TI  - Asymptomatic Leishmania infection: a new challenge for Leishmania control.
AB  - Visceral leishmaniasis (VL) is a serious parasitic disease, causing high
      morbidity and mortality in the developing world. The pathogenesis of VL is
      complex, and the clinical presentation ranges from asymptomatic infection to
      severe and fatal disease. Despite a wealth of research on the full-blown
      "clinical VL" syndrome, asymptomatic leishmania infections remain poorly
      understood. Asymptomatic infection could present a major challenge for control
      programs if its infectiousness is confirmed. In this viewpoint, we highlight the
      crucial knowledge gaps as well as the obstacles in research on asymptomatic
      leishmanial infection. Research in this area is essential for the development of
      more-effective VL control strategies. 

PMID- 24585565
TI  - Racial disparities in invasive Streptococcus pneumoniae infections, 1998-2009.
AB  - BACKGROUND: Before the introduction of 7-valent pneumococcal conjugate vaccine
      (PCV7), invasive pneumococcal disease (IPD) rates among blacks were twice the
      rates in whites. We measured the effects of trends in PCV7-type and non-PCV7-type
      IPD rates on racial disparities in overall IPD and estimated the proportion of
      IPD caused by serotypes included in the 13-valent pneumococcal conjugate vaccine
      (PCV13). METHODS: We analyzed data from the Active Bacterial Core surveillance
      system, which performs active, laboratory- and population-based surveillance for
      IPD for 29.2 million people in the United States, for the period 1998-2009. For
      patients with unknown race, we multiplied imputed race to calculate age-, race-,
      and serotype-specific IPD incidence rates. RESULTS: During 1998-2009, 47 449 IPD
      cases were identified; race was unknown for 5419 (11%). After multiple
      imputation, 31 981 (67%) patients were considered white and 13 750 (29%) black.
      PCV7-type IPD rates in all ages in both races decreased to <1 case per 100 000,
      whereas there were no decreases in overall IPD rates after 2002. By 2009, PCV13
      serotypes caused 71% of cases among whites aged <5 years compared with 58% among
      blacks (P < .01). PCV13 serotypes caused 50% of IPD cases in whites aged >=5
      years compared with 43% among blacks (P < .01). CONCLUSIONS: Despite near
      elimination of PCV7-type IPD in both races, overall disparities in IPD rates
      persisted because non-PCV7-type IPD rates are higher among blacks. Whereas PCV13
      introduction may reduce racial disparities in IPD, higher valency conjugate
      vaccines and strategies to directly address underlying causes are needed to
      eliminate IPD disparities.

PMID- 24585566
TI  - Early warning indicators for HIV drug resistance in adults in South Africa at 2
      pilot sites, 2008-2010.
AB  - BACKGROUND: Approximately 5.2 million people in South Africa were infected with
      human immunodeficiency virus (HIV) by the year 2010, with just over 30% initiated
      on highly active antiretroviral therapy by 2011. With such numbers involved, the
      potential for the emergence of HIV drug resistance (HIVDR) is high. This study
      piloted early warning indicators (EWIs) for HIVDR at 2 clinics in South Africa.
      METHODS: HIV-infected individuals aged >=15 years and receiving antiretroviral
      drugs were enrolled into this cohort study between March 2008 and February 2010.
      All analyses were performed using the 2012 World Health Organization EWI score
      card. RESULTS: A total of 1144 subjects were enrolled. Clinic A reached the
      target for 2 of the 5 EWIs but missed the desired target for on-time pill pickup,
      pharmacy stockouts, and virological suppression. Clinic B reached the target for
      1 of 4 EWIs, namely, dispensing practices. Targets were missed for on-time pill
      pickup, retention in care, and virological suppression. Pharmacy stockouts could
      not be calculated at this site. CONCLUSIONS: Actual performance against the
      levels that the pilot sites should reach to minimize HIVDR was low. Improvements
      in follow-up procedures, internal adherence support, monitoring for drug
      stockouts, and adherence are all aspects that need support to ensure that all
      records are complete. This pilot study may help to inform the South African
      government as EWI monitoring is implemented.

PMID- 24585568
TI  - Editorial commentary: Disparities in invasive pneumococcal disease rates between
      populations: will the extended pneumococcal conjugate vaccines be a game-changer?

PMID- 24585567
TI  - Prevention and treatment of opportunistic infections in HIV-infected adults and
      adolescents: Updated Guidelines from the Centers for Disease Control and
      Prevention, National Institutes of Health, and HIV Medicine Association of the
      Infectious Diseases Society of America.
AB  - In May 2013, a revised and updated version of the Centers for Disease Control and
      Prevention/National Institutes of Health/HIV Medicine Association Guidelines for
      Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and
      Adolescents was released online. These guidelines, since their inception in 1989,
      have been widely accessed in the United States and abroad. These guidelines have
      focused on the management of HIV/AIDS-related opportunistic infections that occur
      in the United States. In other parts of the world, the spectrum of complications
      may be different and the resources available for diagnosis and management may not
      be identical to those in the United States. The sections that have been most
      extensively updated are those on immune reconstitution inflammatory syndrome,
      tuberculosis, hepatitis B, hepatitis C, human papillomavirus, and immunizations.
      The guidelines will not be published in hard copy form. This document will be
      revised as needed throughout each year as new data become available.

PMID- 24585569
TI  - Complete regression of early-stage gastric diffuse large B-cell lymphoma in an
      HIV-1-infected patient following Helicobacter pylori eradication therapy.

PMID- 24585570
TI  - Trial sequence meta-analysis can reject false-positive result calculated from
      conventional meta-analysis.

PMID- 24585573
TI  - Hydroxyurea-associated acral erythema in a patient with polycythemia vera.

PMID- 24585571
TI  - A functional N-terminal domain in C/EBPbeta-LAP* is required for interacting with
      SWI/SNF and to repress Ric-8B gene transcription in osteoblasts.
AB  - The chromatin remodeling complex SWI/SNF and the transcription factor C/EBPbeta
      play critical roles in osteoblastic cells as they jointly control transcription
      of a number of bone-related target genes. The largest C/EBPbeta isoform, LAP*,
      possesses a short additional N-terminal domain that has been proposed to mediate
      the interaction of this factor with SWI/SNF in myeloid cells. Here we examine the
      requirement of a functional N-terminus in C/EBPbeta-LAP* for binding SWI/SNF and
      for recruiting this complex to the Ric-8B gene to mediate transcriptional
      repression. We find that both C/EBPbeta-LAP* and SWI/SNF simultaneously bind to
      the Ric-8B promoter in differentiating osteoblasts that repress Ric-8B
      expression. This decreased expression of Ric-8B is not accompanied by significant
      changes in histone acetylation at the Ric-8B gene promoter sequence. A single
      aminoacid change at the C/EBPbeta-LAP* N-terminus (R3L) that inhibits C/EBPbeta
      LAP*-SWI/SNF interaction, also prevents SWI/SNF recruitment to the Ric-8B
      promoter as well as C/EBPbeta-LAP*-dependent repression of the Ric-8B gene.
      Inducible expression of the C/EBPbeta-LAP*R3L protein in stably transfected
      osteoblastic cells demonstrates that this mutant protein binds to C/EBPbeta-LAP*
      target promoters and competes with the endogenous C/EBPbeta factor. Together our
      results indicate that a functional N-terminus in C/EBPbeta-LAP* is required for
      interacting with SWI/SNF and for Ric-8B gene repression in osteoblasts.

PMID- 24585574
TI  - Cutaneous metastases during an aggressive course of Xp11.2 translocation renal
      cell carcinoma in a teenager.
AB  - We reported a rare case of cutaneous metastases of renal cell carcinoma (RCC)
      with an Xp11.2 translocation in a 15-year-old female. Clinicians should be aware
      of the possibility of this uncommon site of metastasis, which can indicate
      multivisceral dissemination of the disease. We discuss the feasibility and
      opportunity of treating such a patient with multiple line of tyrosine kinase
      inhibitor (TKI) targeting vascular endothelial and platelet-derived growth factor
      receptors.

PMID- 24585572
TI  - Consistent SMARCB1 homozygous deletions in epithelioid sarcoma and in a subset of
      myoepithelial carcinomas can be reliably detected by FISH in archival material.
AB  - Epithelioid sarcomas (ES) are mesenchymal neoplasms subclassified into distal and
      proximal subtypes based on their distinct clinical presentations and histologic
      features. Consistent loss of SMARCB1 nuclear expression has been considered as
      the hallmark abnormality for both subtypes, a feature shared with atypical
      teratoid/rhabdoid tumor of infancy (ATRT). While virtually all ATRTs harbor
      underlying SMARCB1 somatic or germline alterations, mechanisms of SMARCB1
      inactivation in ES are less well defined. To further define mechanisms of SMARCB1
      inactivation a detailed molecular analysis was performed on 40 ES (25 proximal
      and 15 distal ES, with classic morphology and negative SMARCB1 expression) for
      their genomic status of SMARCB1 and related genes encoding the SWI/SNF subunits
      (PBRM1, BRG1, BRM, SMARCC1/2 and ARID1A) by FISH using custom BAC probes. An
      additional control group was included spanning a variety of 41 soft tissue
      neoplasms with either rhabdoid/epithelioid features or selected histotypes
      previously shown to lack SMARCB1 by IHC. Furthermore, 12 ES were studied by array
      CGH (aCGH) and an independent TMA containing 50 additional ES cases was screened
      for Aurora Kinase A (AURKA) and cyclin D1 immunoexpression. Homozygous SMARCB1
      deletions were found by FISH in 36/40 ES (21/25 proximal-type). One of the distal
      type ES displayed homozygous SMARCB1 deletion in the tumor cells, along with a
      heterozygous deletion within normal tissue, finding confirmed by array CGH. None
      of the proximal ES lacking homozygous SMARCB1 deletions displayed alterations in
      other SWI/SNF subunits gene members. Among controls, only the SMARCB1
      immunonegative myoepithelial carcinomas displayed SMARCB1 homozygous deletions in
      3/5 cases, while no gene specific abnormalities were seen among all other
      histologic subtypes of sarcomas tested regardless of the SMARCB1 protein status.
      There was no consistent pattern of AURKA and Cyclin D1 expression. The array CGH
      was successful in 9/12 ES, confirming the SMARCB1 and other SWI/SNF genes copy
      numbers detected by FISH. Our study confirms the shared pathogenesis of proximal
      and distal ES, showing consistent SMARCB1 homozygous deletions. Additionally we
      report the first ES case associated with a SMARCB1 constitutional deletion,
      establishing a previously undocumented link with ATRT. Alternative mechanisms of
      SMARCB1 inactivation in SMARCB1-disomic ES remain to be identified, but appear
      unrelated to large genomic abnormalities in other SWI/SNF subunits.

PMID- 24585575
TI  - The antiquity of riverine adaptations in Iniidae (Cetacea, Odontoceti) documented
      by a humerus from the late Miocene of the Ituzaingo Formation, Argentina.
AB  - "River dolphins" are a paraphyletic group of toothed whales (Odontoceti) that
      represent independent secondary invasions of freshwater habitats. Different
      "river dolphin" lineages display suites of convergent morphological
      specializations that commonly reflect adaptations to riverine and freshwater
      environments, such as longirostry, reduced orbits, and wide, paddle-like
      flippers. One lineage, the Iniidae, is presently endemic to South America, and
      includes several extinct Neogene taxa along with their sole extant genus, Inia
      (the Amazon River dolphin). We report here a humerus recovered from the late
      Miocene deposits of the Ituzaingo Formation in the Parana Basin of Argentina. The
      specimen exhibits diagnostic features of the family Iniidae, including a scapular
      sternal joint of the humerus, which is a unique anatomical connection among
      mammals. This joint permits enhanced parasagittal adduction of the flipper as a
      control surface, relative to other odontocetes, providing Inia with a high degree
      of maneuverability in its structurally complex and heterogenous riverine habitat.
      This unique anatomical connection, here documented from the late Miocene (~9
      million years-6.5 million years old), not only provides the oldest diagnostic
      record for Iniidae, but it also indicates a similar habitat use for this lineage,
      a finding coincident with the current paleoenvironmental interpretation for the
      Ituzaingo Formation.

PMID- 24585578
TI  - Andrea Pasta (1706-1782), eclectic scholar of anatomy and clinical medicine,
      communication and the history of art.
AB  - Andrea Pasta was an eclectic visionary light years ahead of his time. He made
      numerous contributions to the field of medicine, some recognized by his
      contemporaries and others so visionary that they are being applied only in modern
      times. His contributions spanned the disciplines of psychology, gynaecology,
      haematology, infectious diseases and the doctor-patient relationship. Well known
      among his contemporaries, he combined a passion for clinical medicine and a keen
      interest in history and art with a strict research methodology and an approach to
      caring for patients as human beings. By studying his life and works, we can
      better understand the magnitude and significance of his innovative method and its
      applicability in modern times and also the significance of his many
      contributions. 

PMID- 24585579
TI  - A hotbed of medical innovation: George Kellie (1770-1829), his colleagues at
      Leith and the Monro-Kellie doctrine.
AB  - The Monro-Kellie doctrine is named after two Scottish doctors, the well-known
      Alexander Monro secundus and George Kellie, whose life and work has not
      previously been described in detail. After service as a naval surgeon, Kellie
      followed his father into a career as a surgeon in the port of Leith, near
      Edinburgh. His publications show him to be a compassionate and observant doctor,
      ready to question established concepts. He worked closely with surgical
      colleagues in the town, some of whom made important contributions in their own
      right. The paper which led to eponymous fame was based on post-mortem
      observations on the volume of blood in the cerebral blood vessels, which led him
      to conclude that a change in volume of one intracranial constituent must be
      compensated by a reciprocal change in the others. He collaborated with Monro in
      this work but the doctrine was disseminated by another colleague, John
      Abercrombie, in his widely read book on neuropathology. Kellie achieved
      recognition within the local medical community. The doctrine which bears his name
      remains fundamental to our understanding of pressure and volume relationships
      within the cranium. 

PMID- 24585580
TI  - Samuel Holden Parsons Lee (1772-1863): American physician, entrepreneur and
      selfless fighter of the 1798 Yellow Fever epidemic of New London, Connecticut.
AB  - Samuel Holden Parsons Lee practised medicine at a time when the germ theory of
      disease had not yet been proposed and antibiotics remained undiscovered. In 1798
      he served selflessly as the only physician in town who was willing to battle the
      Yellow Fever outbreak of New London, Connecticut. Because he practised at the
      dawn of the age of patent medicine, unfortunately his name also came to be
      associated with medical quackery. We argue that his contributions have been
      grossly underestimated. He compounded and vended medications - including bilious
      pills and bitters - that were gold standards of the day. Moreover, one
      preparation for treatment of kidney stones led to his sub-specialization in this
      field and was met with such success that its sale continued for nearly 100 years
      after his death. While a talented medical man, Lee also had a knack for business,
      finding success in trading, whaling and real estate. 

PMID- 24585581
TI  - Ruminations on Hildegard of Bingen (1098-1179) and autism.
AB  - The article brings together contemporary research on autism spectrum disorder and
      historical sources concerning the medical condition of a 12th century nun,
      Hildegard of Bingen, to test two hypotheses: first, that Hildegard manifested
      disabilities that meet the criteria for autism spectrum disorder and, second,
      that medieval monasticism was unwittingly well-suited to treat Hildegard's
      condition. Abundant Hildegardian sources document traces of autism spectrum
      disorder behaviour in Hildegard's unusual childhood and the composite picture
      that emerges, when these individual traits are gathered together, is consistent
      with an autism spectrum disorder diagnosis. The role monasticism played in
      helping Hildegard overcome these behaviours is documented and aspects that
      monasticism shares with modern autism spectrum disorder treatment programs are
      identified. By recognizing the presence of autism spectrum disorder traits in a
      major cultural leader of another era and by identifying the type of life she
      lived while those traits were minimized, we gain insight into the history of
      autism, medieval monastic life and effective elements of autism spectrum disorder
      treatment. 

PMID- 24585582
TI  - The Professor and the Student, Sir Ronald Aylmer Fisher (1890-1962) and William
      Sealy Gosset (1876-1937): Careers of two giants in mathematical statistics.
AB  - Sir Ronald Aylmer Fisher and William Sealy Gosset were responsible for laying the
      foundations of statistical inference. Tests that bear their names are used by
      students and researchers in a wide variety of scientific disciplines. Similar and
      different in many respects, their lives and careers are the subject of this
      essay. They were not teacher and pupil; in fact the student was 14 years older
      than the professor. Their careers did not require them to interact with one
      another much but they were aware of one another's work. Although Sir Ronald is
      assigned the role of the professor, his success as a teacher was impaired by his
      inability to understand the limitations of his students. Meanwhile Gosset was
      forced to publish his work under the pseudonym 'Student' in order to make
      contributions to the field of mathematical statistics. Both men are undisputed
      giants in the field of statistics and we celebrate their achievements as much as
      we try to understand their struggles. 

PMID- 24585583
TI  - Dr Amos G Babcock - fact or fiction?
AB  - The War of 1812-14 between the United States of America and Great Britain gave
      rise to several journals relating the sufferings of prisoners of war confined in
      prison ships and gaols in England. One of these is A Journal of a Young Man from
      Massachusetts, said to have been written by Dr Amos G Babcock, an American ship's
      surgeon, and first published in 1816. This article sets out arguments for and
      against the truth of this assertion. 

PMID- 24585584
TI  - Professor Tyndale John Rendle-Short (1919-2010), British and Australian
      paediatrician: A life in two domains.
AB  - Professor Tyndale John Rendle-Short (1919-2010), a British and Australian
      paediatrician, lived a professional life of considerable influence in two domains
      - academic paediatrics and fundamentalist theology. A Cambridge medical graduate
      (1943) and doctor-soldier, he was appointed as the Foundation Professor of Child
      Health at the University of Queensland (1961). In Australia, he was a pioneer in
      three paediatric developments ('rooming-in' for mothers in hospitals, autism
      research and cystic fibrosis). His A Synopsis of Children's Diseases was
      published in six editions, was translated into three languages and was used as a
      standard paediatric textbook on four Continents. Distinct from this clinical
      domain, as a passionate anti-Darwinist his fundamentalist theology was that
      variously self-described as 'theistic evolution' (believing in 'progressive
      Creationism') and later that of 'six-literal day young-earth Creation'. He
      established and was the Foundation Chairman of the Creation Science Foundation
      (UK) and was World Chairman of the US-based Creation Ministries International.
      This biography is a record of this perhaps paradoxical and unique life. 

PMID- 24585585
TI  - Roy Lee Moodie (1880-1934) and the beginnings of palaeopathology.
AB  - Roy Lee Moodie was a geologist whose interest in ancient disease was stimulated
      by his finding of pathological change in some of the fossils that he studied,
      including many from the Rancho La Brea site in California. He occupied teaching
      positions in Chicago, Dallas and Santa Monica and in 1928 began an acquaintance
      and a correspondence with Henry Wellcome who was then in the United States and
      appearing before the Senate Committee on Foreign Affairs. Moodie persuaded
      Wellcome to sponsor his palaeopathological work and the following year he was
      appointed palaeopathologist to the Wellcome Historical Medical Museum (WHMM) at a
      salary of six thousand dollars a year, the first person to hold such a title and
      the first and only occupant of the title at the WHMM or its successor
      organisations. He published extensively from 1915 until his death in 1934,
      including his great compendium Paleopathology; an Introduction to the Study of
      Ancient Evidences of Disease, and the collected papers of Sir Marc Armand Ruffer.
      He is perhaps best remembered or, at least, most widely quoted for attributing
      the beginnings of palaeopathology to a publication of Esper in 1774 although the
      passage in which he did so contained two major errors that have been perpetuated
      in the literature ever since, the authorship of the publication and the diagnosis
      of the lesion that he supposed began the study of disease in antiquity. 

PMID- 24585586
TI  - Professor Yakov Yulievich Bardakh (1857-1929): pioneer of bacteriological
      research in Russia and Ukraine.
AB  - Odessa physician Yakov Bardakh had an unusually high number of bacteriological
      'firsts' to his credit: in 1886, while working at the Odessa Bacteriological
      Station, he was the first to test Louis Pasteur's anti-rabies vaccine on himself
      in order to demonstrate its safety. In the 1890s, in addition to conducting
      pioneering research on diphtheria, he created the first extensive course in
      bacteriology at the Novorossiya University--the first such course in Russia--and
      established the first university laboratory in Russia to specialize in
      bacteriology. In 1903 he created the first Medical Emergency Service in Russia.

PMID- 24585587
TI  - The education of Ehrenfried Walther von Tschirnhaus (1651-1708).
AB  - Ehrenfried Walther von Tschirnhaus, mathematician, inventor, and correspondent of
      Spinoza, is often thought to have studied medicine at Leiden, though
      documentation of this fact has been lacking. Tschirnhaus' medical education is
      here documented, along with the nature of his medical practice. 

PMID- 24585588
TI  - Crooked Timber: The life of Calvin Wells (1908-1978).
AB  - Calvin Wells was the leading palaeopathologist in the UK between the later 1950s
      and the early 1970s. He studied medicine at University College London but failed
      in anatomy and qualified in 1933 with the Conjoint Diploma (MRCS, LRCP). After
      qualification he began to study obstetrics and after war service in the RAMC he
      settled in Norfolk (UK), established a small general practice and took up
      palaeopathology. Although he was usually conservative in diagnosis he tended to
      over-interpret signs in the skeleton, often publishing descriptions that were
      more fiction than science. He held firm views on the way in which palaeopathology
      should be undertaken and in particular he resented the entry into the field of
      anthropologists without medical training. His major contributions to
      palaeopathology were related to the study of cremations and the introduction of
      the notion of pseudopathology, and his writings on these subjects have scarcely
      been improved upon since. He was extremely well read, warm and encouraging to
      those with archaeological or medical qualifications, but vituperative about those
      he disliked. His bone reports, which are a major proportion of his published
      output, generally were highly regarded but his writing is often marred by sexual
      innuendo and vulgarity which does his memory little credit. 

PMID- 24585589
TI  - Queen Cleopatra and the other 'Cleopatras': their medical legacy.
AB  - Cleopatra is a female figure widespread in Greece (especially in Macedonian
      territory), Egypt and Syria during the Hellenistic era. Ancient women doctors
      bearing the name Cleopatra have been identified by a systematic search through
      the ancient Greek, Latin and Egyptian bibliography, including original resources
      from the first century BC. Fictional and non-fictional figures have been
      distinguished and their works identified. Queen Cleopatra of Egypt, Galen's
      physician assistant, the outcast Metrodora, Cleopatra the Alchemist and Cleopatra
      the Gynaecologist deliver a story of medicine and name-giving that confuses
      researchers of the past and intrigues those of the present. 

PMID- 24585590
TI  - The eponymous Dr James Marion Sims MD, LLD (1813-1883).
AB  - Dr James Marion Sims was born in 1813 in Lancaster County, South Carolina. It was
      while pioneering numerous surgical procedures in Alabama that in 1849 he achieved
      the outstanding landmark in medical history of successfully, and consistently,
      repairing vesicovaginal fistulae. Sims soon developed a reputation as a fine
      surgeon, with new operations and techniques, using novel surgical instruments and
      his innovative approaches frequently published. Moving to New York City in 1853,
      he further established hospitals devoted entirely to women's health. Sims was
      controversial, with flamboyant descriptions of self-confident success, yet they
      were tempered with sober reflection of failure and loss. Today we remain with the
      Sims speculum and Sims position, eponymous tributes to his accomplishments as the
      'Father of Gynaecology'. 

PMID- 24585591
TI  - Augustus Bozzi Granville (1783-1872): Pioneer obstetrician and gynaecological
      surgeon who performed the first scientific autopsy of a mummy.
AB  - AB Granville was a pioneer obstetrician and gynaecologic surgeon who performed
      the world's first myomectomy and the first ovariotomy in England. He also
      performed the first scientific autopsy of an Egyptian mummy, discovering the
      oldest known ovarian tumour. He thought it was malignant and caused her death
      from 'ovarian dropsy'. This study reveals the tumour to be a benign cystadenoma.
      Further analysis indicates she died from terminal pneumonia from tuberculosis. 

PMID- 24585592
TI  - A newly identified apothecary in Boswell's Life of Johnson: Edward Ferrand (1691
      1769).
AB  - Ever since the publication of James Boswell's Life of Samuel Johnson (1791), it
      has been known that Johnson's young servant, the former slave Francis Barber 'ran
      away' at one point and worked for a London apothecary. But the apothecary was not
      named by Boswell and has not been identified by any of Johnson's numerous
      biographers nor in recent studies of Francis Barber. Research in surviving
      Boswell manuscripts, 18th-century London guides and the archives of the Society
      of Apothecaries prove the apothecary to have been Edward Ferrand. This article
      sets out the circumstances in which the reference to the anonymous apothecary
      came to appear in the Life of Johnson and reconstructs Ferrand's life and career.
      Examining Ferrand's origins, his social circumstances and his career, a case
      study is presented of a successful practitioner of the profession of apothecary
      in early Georgian Britain and a suggestion made as to why the distinguished
      apothecary came to provide a place of refuge for a teenaged runaway servant who
      had been a slave until he was about nine years old. 

PMID- 24585593
TI  - Sir Archibald Hector McIndoe (1900-1960) and the Guinea Pig Club: the development
      of reconstructive surgery and rehabilitation in the Second World War (1939-1945).
AB  - This article discusses the work of pioneering surgeon Sir Archibald McIndoe and
      particularly his reconstructive surgery and patient-centred approach during the
      Second World War. It also covers how this affected the lives of his patients and
      the subsequent formation of the Guinea Pig Club.

PMID- 24585594
TI  - The mysterious fate of la Bibliotheque de Louis Pasteur (1822-1895).
AB  - In addition to the holdings at Bibliotheque Nationale de France and Musee du
      Pasteur Institut a Paris, major parts of la Bibliotheque de Louis Pasteur are in
      four institutions in the United States - Reynolds Historical Library at the
      University of Alabama at Birmingham, Alabama; Burndy Library on the History of
      Science and Technology at Huntington Library in San Marino, California; Harry
      Ransom Humanities Research Center at University of Texas in Austin, Texas; and
      Truman G Blocker History of Medicine Collections, The Moody Medical Library,
      University of Texas Medical Branch, Galveston, Texas. The circuitous paths that
      led each part of la Bibliotheque de Louis Pasteur to their present locations were
      traced and the lives of key individuals in medicine, science and the humanities
      who obtained these valuable documents were recounted. The documents in each
      institution were discussed and a plan was considered to make them accessible to
      scholars who wish to further explore the life of Louis Pasteur. 

PMID- 24585595
TI  - Giuseppe Moscati (1880-1927): a holistic approach to medicine.
AB  - Giuseppe Moscati was a physician, medical school professor and a pioneer in the
      field of biochemistry and Italian studies on diabetes. He was declared a Catholic
      saint in 1987. In order to respond better to both the physical and spiritual
      needs of his patients, he developed his own holistic approach to healthcare
      involving meticulous drug regimens, meditation and discipline. 

PMID- 24585596
TI  - Discovery of why acute lymphoblastic leukaemia cells are killed by asparaginase:
      Adventures of a young post-doctoral student, Bertha K Madras.
AB  - A surprising finding was made by JG Kidd (1909-1991) that guinea pig serum could
      make tumours disappear in mice. A later finding made by JD Broome (1939-) showed
      that asparaginase could suppress or kill tumour cells. However, the major mystery
      was why were only tumour cells but not normal cells affected by the asparaginase?
      The biology underlying this mechanism was unravelled by a young post-doctoral
      student, Bertha K Madras (1942-) who hypothesized that cells with low asparagine
      synthetase are those that die following treatment with asparaginase. To test her
      theory, Madras developed an assay for asparagine synthetase. The hypothesis was
      supported by the results that cells with normal asparagine synthetase were
      protected, while cells with low levels of this enzyme were killed by
      asparaginase. The findings provide a clinical guide for the use of asparaginase
      in acute lymphoblastic leukaemia in children and adults. 

PMID- 24585597
TI  - Jane Austen (1775-1817) and the cultural history of health.
AB  - This paper provides a review of some aspects of the life and novels of Jane
      Austen that have particular bearing on her approach to issues of sickness and
      health. It is based on a Keynote Lecture given at the Annual Congress of the
      British Society for the History of Medicine on 1 September 2011 at the University
      of Surrey. 

PMID- 24585598
TI  - Did Mozart suffer from Asperger syndrome?
AB  - The most reliable biographies of Mozart highlight elements that are compatible
      with current diagnostic criteria for Asperger syndrome including qualitative
      impairment in social interaction and stereotyped and repetitive motor mannerisms.
      Furthermore, numerous features are documented including difficulty in
      communicating his emotional state and in inferring the mental state of his
      interlocutors, motor clumsiness, specific skills and genius, left-handedness,
      special sense of humour, physical developmental abnormalities, bizarre thinking,
      overvalued ideas and delusions. 

PMID- 24585599
TI  - A memoir of Sir John Forbes (1787-1861).
AB  - The 150th anniversary of the death of Sir John Forbes passed on 13 November 2011
      perhaps unnoticed except in his native land. This memoir is an attempt to remind
      the medical profession of some of his achievements and of the value of percussion
      and auscultation in the bedside diagnosis of diseases of the heart and lungs. 

PMID- 24585601
TI  - Harrison's Grooves - Edwin Harrison (1779-1847) or Edward Harrison (1766-1838)?

PMID- 24585600
TI  - Florence Nightingale (1820-1910) and Sir John Forbes (1787-1861): neighbours in
      Old Burlington Street, Westminster.
AB  - The year 2010 marks the centenary of the birth of Florence Nightingale and will,
      no doubt, be universally remembered. Her life and nursing career have recently
      been fully described by Bostridge. It is less well known that her neighbour from
      November 1856 was the distinguished Scottish physician Sir John Forbes MD Edin
      FRCP Lond FRS DCL Oxon. Although they never met, they exchanged copies of each
      other's books and shared a mutual respect. 

PMID- 24585602
TI  - The King's anaesthetic.
AB  - King George VI underwent an operation for pneumonectomy in September 1951. Part
      of the operation anaesthetic record has survived. With conjecture, on a typical
      scenario of a 55-year-old male undergoing pulmonary resection for carcinoma in
      the early 1950s and other facts in the public domain, the King's anaesthetic has
      been reconstructed to give an approximation of the events that in the last few
      months of his life caused his speech to change from that achieved by his personal
      voice coach and recently portrayed on celluloid in the film 'The King's Speech'.
      The popularity and success of the film 'The King's Speech' brought to mind that
      King George VI died of bronchogenic carcinoma, a result, not recognised at the
      time, of the cigarette smoking habit that is a prominent feature of the story in
      celluloid. 

PMID- 24585603
TI  - Nicholas Culpeper (1616-1654): London's first general practitioner?
AB  - Nicholas Culpeper is often regarded as an ill-disciplined, maverick, mid-17th
      century herbalist and the father of contemporary alternative medicine. There are
      elements of this statement that have some truth but to dismiss his contribution
      to the development of health provision in London at the time would be a great
      injustice. Culpeper did not complete his apprenticeship as an apothecary and was
      not a formally trained physician, but he developed a clinical practice for the
      poor of London, indistinguishable from the role of the present day general
      practitioner. Observers at the time recognised his concern and compassion and his
      commitment to treat the whole patient and not just the disease. His enduring
      contribution was his translation from Latin of the physicians' Pharmacopoeia
      Londinensis which could be regarded as the first major step towards the
      demystification of medicine. Culpeper's London Dispensatory and the many other
      medical treatises that followed were affordable and widely available to the
      common man. Culpeper antagonised both apothecaries and physicians because he
      breached the regulations of the day by accepting patients directly. So perhaps
      Culpeper was, de facto, London's first general practitioner, at least 150 years
      before the role was formally recognised in the Apothecaries Act 1815. 

PMID- 24585604
TI  - Medical missionaries to China: the antecedents.
AB  - Notwithstanding the traditional belief that disciples of Jesus Christ introduced
      Christianity into China, conclusive evidence showed that it was the Nestorian
      missionaries who entered China in AD 635. Alongside commercial contacts between
      the West and China during the prosperous T'ang dynasty (618-906), trepanation,
      bloodletting and the universal antidote theriac were introduced from the
      Byzantium Empire. Nestorian Christians built churches throughout China and
      offered some form of medical services. During the Yuan (Mongol) dynasty (1260
      1368), foreign physicians were present in the Royal Court; the most famous was
      the astronomer, linguist and physician Ai-hsieh (Isaiah), Head of the Imperial
      Medical Bureau. With the fall of this dynasty, Christianity, being primarily the
      faith of a foreign community, naturally fell into oblivion. It was not until the
      sixteenth-century's Age of Discovery when a safe sea route to China was found
      that a new phase of Christian missionaries began. 

PMID- 24585605
TI  - William Adams' (1810-1890) 'subcutaneous' osteotomy saw.

PMID- 24585606
TI  - Maria Polydouri (1902-1930): the Greek poete maudit who died of tuberculosis.
AB  - Maria Polydouri was a notable Greek poet. Often likened to the French poetes
      maudits, her poetry reflected a lyrical charisma and her unsettled life an
      untimely ending. The passing of both her parents within less than two months when
      she was aged 18 and her incomplete, desperate affair with the syphilitic poet
      Kostas Karyotakis, defined her existence. She took up many uncompleted
      occupations and remained socially committed. It seems that in 1923 she caught
      tuberculosis that was diagnosed ultimately in 1927 and led to her hospitalization
      at first in Paris and later in Athens. A progressive and restless spirit until
      the end, she wrote her best poems while in hospital. Polydouri's final years and
      death received national attention and marked her out as a Greek literary legend. 

PMID- 24585607
TI  - Headache in the writings of Elizabeth Gaskell (1810-1865).
AB  - Mrs Elizabeth Gaskell was a celebrated author of the Victorian era, a friend of
      both Charles Dickens and Charlotte Bronte and the latter's first biographer.
      References to headache in Mrs Gaskell's six major novels, published between 1848
      and 1866 as well as some of her shorter fiction, have been collated. These
      multiple references suggest that Elizabeth Gaskell used headache as a narrative
      device, possibly based on her own experience of headache and that of female
      acquaintances, most notably Charlotte Bronte. 

PMID- 24585608
TI  - Poet and profligate: the secrets of Aleksandr Sergeyevich Pushkin's (1799-1837)
      personality and maladies.
AB  - Aleksandr Sergeyevich Pushkin (1799-1837) was one of the great figures of Russian
      poetry and literature. There are numerous publications about his life, adventures
      and creative work. However, little has been written about his character, mental
      state and the condition of his wound during his fatal duel. Furthermore, his
      sexual illnesses and their nature were discussed even less. This paper attempts
      to lift the veil from this mystery. 

PMID- 24585609
TI  - Dr Charles Morehead MD (Edinburgh), FRCP (1807-1882): Pioneer in medical
      education.
AB  - Charles Morehead studied medicine in Edinburgh and Paris. Among his teachers were
      George Jardine (1742-1827) (moral philosophy), Professor William Pulteney Alison
      (1790-1859) (medicine), Pierre Louis (1787-1872) and Rene Laennec (1781-1826). He
      joined as Assistant Surgeon in the Bombay Medical Service of the East India
      Company and was appointed to the staff of Governor Sir Robert Grant (1779-1838).
      Grant and Morehead founded the Grant Medical College and Sir Jamsetjee Jejeebhoy
      (1811-1877) Hospital in Bombay. Morehead established standards of medical
      education at these institutions far superior to those in Calcutta and Madras and,
      in some ways, to those in Britain. His emphasis on discipline, regular
      attendance, learning medicine at the bedside, the maintenance of detailed records
      on all patients and thorough evaluation of the progress made by students were
      salutary. While in London to recover his health, he wrote his classic book
      Clinical Researches on Disease in India for Indian doctors and those from Britain
      entering the Indian Medical Services. He lived in Edinburgh after retirement from
      India but continued to help teachers and students at his institutions in Bombay. 

PMID- 24585610
TI  - Gods behaving badly.
AB  - This paper addresses the myths surrounding the birth and death of Asclepios, the
      popular healing God of the Greeks and his place among other deities of the Greek
      Pantheon. The enigmatic invocation of Asclepios by Socrates, the Athenian
      philosopher condemned to take the hemlock, in his final moments is also
      discussed. 

PMID- 24585611
TI  - Medical Memorial: Sir James Young Simpson (1811-1870).

PMID- 24585612
TI  - Nikolay Ivanovich Pirogov (1810-1881) and Bernhard von Langenbeck (1810-1887):
      similarities on the anniversary of their 200th birthdays.
AB  - The year 2010 marked the 200th anniversary of the birth of two great surgeons,
      the German Bernard von Langebeck and the Russian Nikolay Ivanovich Pirogov. The
      anniversary was celebrated throughout the world and in Russia where the year 2010
      was declared 'The Year of Pirogov'. However, in England the work of these men is
      not well known and is little appreciated. Both men were born in the same month of
      the same year in different countries with different cultures. Despite the
      contrasts, the similarities between their lives are striking. This paper explores
      the parallels between their lives and their contributions to the field of
      surgery. The work of both men prepared the ground for the work of Joseph Lister
      (1827-1912) in Glasgow (1867) and the development of antiseptic techniques. 

PMID- 24585613
TI  - Fryderyc-Francois Chopin (1810-1849): music and malady.
AB  - Chopin was born in Zelazowa Wola in Western Poland. He had no formal piano
      tuition and one could say that his skill as a pianist was self-taught, close to a
      miracle. All his compositions included the piano; this was not a restriction for
      him. The illnesses that plagued him and the cause of his death are the subject of
      articles by retrospective diagnosticians. 

PMID- 24585614
TI  - 'The chearful haunts': John Armstrong (1709-1779), physician, poet, satirist and
      leveller of medical knowledge.
AB  - John Armstrong, the first honours graduate of the University of Edinburgh School
      of Medicine, was famous in his day for a lengthy didactic poem entitled The Art
      of Preserving Health (1744). He is now obscure except to scholars specializing in
      the 18th century and, when discussed at all, often dismissed as a failed
      physician who wrote mediocre poetry in a quest for money and fame. A new exegesis
      by Adam Budd exhumes Armstrong as an original voice who offered timely and
      reassuring advice to Britons as they braced for another epidemic of plague; who
      depicted illness through the lens of a vulnerable and sympathetic physician, and
      who was perhaps above all else a leveller of medical knowledge. Elaborating on
      Budd's thesis, it would seem that Armstrong, a complicated man, has frequently
      been misread and was in some ways ahead of his time. 

PMID- 24585615
TI  - Goldilocks or Granny?: Portrayals of deafness in the English novel.
AB  - This paper examines the portrayal of characters that are deaf in 29 English
      novels written over 300 years by mainstream authors for a largely hearing
      readership. Their attributes are examined with particular reference to the mode
      of communication, education, medical intervention and issues of identity, and as
      to how far these portrayals resonate with the experience of persons with hearing
      loss by comparison to contemporary deaf narratives. The reasons why hearing
      authors include such representations are considered and two categories of iconic
      character are identified--'Goldilocks' and 'Granny', discussing how far these
      portrayals truly inform about deafness or reflect the underlying attitudes of the
      author and the society they represent.

PMID- 24585616
TI  - Sangye Gyatso (1653-1705) and the medical paintings of Tibet.
AB  - Sangye Gyatso played a major role in the politics of 17th century Tibet, and was
      the originator of the medical paintings that encompassed the full scope of
      Tibetan medicine.The depictions became an important aid in medical education, and
      was heavily influenced by Buddhist thinking. The paintings arose in a visual
      culture dominated by religious art. 

PMID- 24585617
TI  - The life and times of Francis Geach MD, FRS (1730-1798), Senior Surgeon to the
      Royal Naval Hospital, Plymouth (1778-1798).
AB  - Francis Geach MD, FRS was surgeon to the Royal Naval Hospital, Plymouth from
      about 1765 until he died in 1798. The son of a sail maker, he was born and raised
      in Plymouth. He was apprenticed to a surgeon in 1745 and probably undertook some
      medical training in London but he spent his professional career in Plymouth as a
      naval surgeon and in private practice. Geach had a particular interest in trauma
      and skin disease and was highly respected as a diagnostic physician, notably of
      inflammatory disorders, but he also had an interest in local issues including the
      cause of Devonshire colic. He was noted for the recognition of the skin disease
      of Francis Beaufort, later Admiral Sir Francis, as Greek leprosy (psoriasis) and
      for the recognition and support he gave to Sir William Knighton, physician and
      private secretary to the Prince Regent, later George IV. This article summarises
      Francis Geach's genealogy, medical and academic practice, his breadth of
      interests and his contribution to Devonshire life in the 18th century. 

PMID- 24585618
TI  - Daniel Alcides Carrion (1857-1885) and a history of medical martyrdom.
AB  - Daniel Carrion, a sixth-year medical student, died while investigating the
      effects of self-inoculation of the causative organism of Oroya Fever and
      Bartonellosis and thereby contributed to understanding of the disease before the
      organisms had been identified. 

PMID- 24585619
TI  - Professor Georgy Nestorovich Speransky (1873-1969): A great soviet paediatrician.
AB  - This paper is a biography of a great Soviet paediatrician, Professor Georgy
      Nestorovich Speransky, known as the founder of Russian neonatology. He was the
      organizer, Director and scientific leader of the first State Research Institute
      of Maternity and Infant Care in the USSR which later was reorganized as the State
      Research Institute of Paediatrics of the Academy of Medical Sciences of the USSR.
      He organized the first Russian medical department of childhood diseases at the
      Central Institute of Continuing Education for Medical Doctors, where he and his
      colleagues taught physiology and pathology. He was one of the initiators of a
      free state system of maternity and infant health care and infant mortality was
      decreased tenfold. 

PMID- 24585620
TI  - Jean-Etienne Esquirol (1772-1840).

PMID- 24585621
TI  - John Hunter's (1728-1793) account of venereal diseases.
AB  - John Hunter's work included description of the nature of digestion, child
      development, role of the lymphatic system and proof that the maternal and foetal
      blood supplies are separate. His contribution to the understanding of venereal
      diseases is reviewed. Hunter's argument of the unitary nature of venereal
      diseases is examined and the progress he made in diagnosis and management is
      discussed. 

PMID- 24585622
TI  - Joseph Erlanger (1874-1965): the cardiovascular investigator who won a Nobel
      Prize in neurophysiology.
AB  - Born in San Francisco in 1874 into the family of German immigrants in which he
      was the only one to proceed beyond elementary education, Joseph Erlanger
      graduated from the University of California (Berkeley) in 1894. He was about to
      enter the local Cooper Medical School when he was told that the new medical
      school in Johns Hopkins University (Baltimore) aimed to surpass all others, and
      there he graduated and was later coached for a career in academic life by William
      H Howell (1860-1945). In due course he held the Chairs of Physiology in the
      University of Wisconsin (Madison) and Washington University at St Louis,
      Missouri. He showed that the Bundle of His is indeed the functional link between
      the atria and the ventricles in the mammalian heart and that the Korotkoff sounds
      are produced by a 'breaker' phenomenon resulting from instability of the pulse
      wave in a partially occluded artery. With Herbert S Gasser (1888-1963) he was
      awarded the Nobel Prize in 1944 for their work on action currents in peripheral
      nerve fibres. The history of science occupied him during his retirement. He died
      at St Louis in 1965. 

PMID- 24585623
TI  - The physician, the Emperor and the fibromyalgia: Charles-Edouard Brown-Sequard
      (1817-1894) and Dom Pedro II (1825-1891) of Brazil.
AB  - The physician Charles-Edouard Brown-Sequard was a neurologist of considerable
      importance. In 1846 his thesis 'Researches and Experiments on the Physiology of
      the Spinal Cord' brought out knowledge about the sensory pathways which remains
      until today. The Emperor, Dom Pedro II was the second and last Emperor of Brazil,
      reigning for 49 years and remembered for defending the nation's integrity, the
      end of slavery, support for education and culture, diplomacy and relations with
      international personalities. He married Dona Teresa Cristina of Bourbon-Two
      Sicilies (1822-1889) by proxy in 1843, the fourth and last Empress consort of
      Brazil. This paper reports the exchange of letters between these personalities of
      the XIX century. Although they lived far from each other and worked in areas so
      different, they discussed the health of the Empress in letters. Dom Pedro II made
      contact with Brown-Sequard hoping that ' ... your knowledge shall help heal my
      wife of nervous disease ... . ' According to Dom Pedro the Empress suffered ' ...
      for a long time with more or less long interruptions of horrible neuralgic pains
      in the legs, head and the scalp. Two points on the dorsal spine feel the effects
      more or less with pressure applied ... . ' In addition to describing and
      documenting the exchange of letters, this paper raises the possibility that the
      Empress suffered from the fibromyalgia syndrome. 

PMID- 24585624
TI  - Sir Astley Paston Cooper (1768-1841): The man and his personality.
AB  - The most acclaimed surgeon of his time, Astley Cooper, a man from Norfolk and a
      student of the eminent John Hunter, was an outstandingly successful surgeon. With
      his accomplishments in surgery and experiments in dissection he soon became a
      prominent figure and received recognition worldwide. At the young age of 21 he
      was appointed Demonstrator in Anatomy at St Thomas's Hospital in London and two
      years later was made Joint Lecturer in Anatomy and Surgery. With his passion for
      anatomy, his love for surgery and his expanding knowledge he became Surgeon to
      Guy's Hospital in 1800 and in the same year was elected a Fellow to the Royal
      Society. His attainments led him to become surgeon to three successive British
      monarchs as well as receiving a bestowal of Baronetcy. Through his edifying
      lectures, fastidious experiments and publications on anatomy and pathology he has
      inspired and enlightened many budding anatomists and surgeons and the principles
      of his teachings still prevail in practice today. 

PMID- 24585625
TI  - Karl Friedrich Meyer (1884-1974): His ambitions, approach and achievements.
AB  - Karl Meyer was one of the outstanding scientists in the areas of medical and
      veterinary microbiology, infectious diseases, pathology, epidemiology, ecology,
      academic education and public health during the first half of the 20th century.
      He was an exceptional scientist with an enormous drive to deepen knowledge and
      understanding, in the interest of the people, to improve diagnosis and treatment
      of many zoonoses including prevention and improvement in health laws. This paper
      presents a survey of the extraordinarily wide-ranging achievements of Meyer and
      his systems approach. 

PMID- 24585626
TI  - Sir John Struthers (1823-1899), Professor of Anatomy in the University of
      Aberdeen (1863-1889), President of the Royal College of Surgeons of Edinburgh
      (1895-1897).
AB  - Between 1841 and 1845 John Struthers attended both the University of Edinburgh
      and some of the various Extra-mural Schools of Medicine associated with Surgeons'
      Hall. While a medical student he became a Member of the Hunterian Medical Society
      of Edinburgh and later was elected one of their Annual Presidents. He graduated
      with the MD Edin and obtained both the LRCS Edin and the FRCS Edin diplomas in
      1845. Shortly afterwards he was invited to teach Anatomy in Dr Handyside's Extra
      mural School in Edinburgh. The College of Surgeons certified him to teach Anatomy
      in October 1847. He had two brothers, and all three read Medicine in Edinburgh.
      His younger brother, Alexander, died of cholera in the Crimea in 1855 while his
      older brother James, who had been a bachelor all his life, practised as a
      Consultant Physician in Leith Hospital, Edinburgh, until his death.When
      associated with Dr Handyside's Extra-mural School in Edinburgh, John taught
      Anatomy there until he was elected to the Chair of Anatomy in Aberdeen in 1863.
      Much of his time was spent in Aberdeen teaching Anatomy and in upgrading the
      administrative facilities there. He resigned from this Chair in 1889 and
      subsequently was elected President of Leith Hospital from 1891 to 1897. This was
      in succession to his older brother, James, who had died in 1891. Later, he was
      elected President of the Royal College of Surgeons of Edinburgh from 1895 to 1897
      and acted as its Vice-President from 1897 until his death in 1899. In 1898, Queen
      Victoria knighted him. His youngest son, John William Struthers, was the only one
      of his clinically qualified sons to survive him and subsequently was elected
      President of the Edinburgh College of Surgeons from 1941 to 1943. 

PMID- 24585627
TI  - Lord Lister's antiseptic steam spray.

PMID- 24585628
TI  - The Arcane of Cinchona and the New Granada Expedition: the multi-dimensional mind
      of Jose Celestino Mutis (1732-1808).
AB  - Jose Celestino Mutis y Bosio was a Spanish physician, naturalist, astronomer,
      priest, theologian and mathematician, and one of the icons of the Enlightment Age
      both in Spain and the American Continent. As the Viceroy's personal doctor, he
      travelled to the territory of New Granada in what is now Colombia. Mutis was the
      creator and first leader of the Royal Botanic Expedition of New Granada to study
      South American wildlife, discovering thousands of new species. He also launched
      several Public Health measures in the Santa Fe area, helping to introduce a
      vaccination campaign. Mutis was the first person to introduce Newtonian physics
      in the Spanish America and he established the first Observatory in the New World
      which is still in use. He was deeply admired and recognized as a prominent
      scientist by great personalities of his time including Carl von Linee and
      Alexander von Humboldt. 

PMID- 24585629
TI  - Jane Cooke Wright (1919-2013): Pioneering oncologist, woman and humanitarian.
AB  - Jane Wright was a fundamental researcher in cancer chemotherapy in the 1950s
      1980s and was one of the first scientists to test anti-cancer drugs on humans
      rather than solely on mice, discovering the use of the popular antimetabolite
      drug methotrexate on solid tumours. From her research she was able to conclude
      which specific anti-cancer agents would have the greatest lethal effect on a
      patient's certain cancer type and she invented a method of delivering
      chemotherapy agents directly to an internal cancer site. During a time when the
      Civil Rights in the United States of America were undergoing a transformation to
      reduce the discrimination and segregation imposed on African Americans and the
      civil rights activist Martin Luther King Jr made a speech to call for an end to
      racism in 1963, Jane Wright became the first African American to hold such a high
      position at a nationally recognised institution and the first woman to be elected
      President of the New York Cancer Society. US President Lyndon B Johnson appointed
      Jane to the President's Commission of Heart Disease, Cancer and Stroke (serving
      1964-1965) and the National Cancer Advisory Board (serving 1966-1970). Jane
      retired in 1987 by which time she had published more than 75 scientific papers,
      led delegations of oncologists in China, the former Soviet Union, Africa and
      Europe and held key positions in various international and national
      organisations. Jane Wright passed away on 19 February 2013 aged 93 but her legacy
      lives on in the name of an award from the American Association of Cancer
      Research. 

PMID- 24585630
TI  - Christian Albrecht Jensen (1792-1870): An artistic illustration of Foville's
      syndrome.
AB  - Foville's syndrome, a neurological brainstem syndrome, was described in France in
      1858. By chance, a talented portrait painter, CA Jensen, probably illustrated the
      syndrome at the same time in Copenhagen. This note illustrates the importance of
      observation in both neurology and art and the variety in interpretation of the
      same picture by viewers. 

PMID- 24585631
TI  - Ibn al-Quff (1233-1286 AD), a medieval Arab surgeon and physician.
AB  - Abu'l-Faraj ibn Ya'qub ibn Ishaq Ibn al-Quff al-Karaki (1233-1286 AD), best known
      as Ibn al-Quff in the West, was a 13(th) century Arab physician-surgeon. During
      his lifetime, Ibn al-Quff made some important contributions to the art of
      healing. He authored several books and commentaries in the field of medicine, in
      particular surgery. This paper aims to review Ibn al-Quff's life, career, and
      contributions to medical science. 

PMID- 24585632
TI  - Photoluminescence shift in frustules of two pennate diatoms and nanostructural
      changes to their pores.
AB  - The diatom silicified cell wall (frustule) contains pore arrays at the micro- to
      nanometer scale that display efficient luminescence within the visible spectrum.
      Morphometric analysis of the size and arrangement of pores was conducted to
      observe whether any correlation exists with the photoluminescence (PL) of two
      diatom species of different ages. UV-excited PL displays four clearly defined
      peaks within the blue-region spectrum, on top of the broad PL characteristic of
      synthetic porous silicon dioxide, recorded for reference and where discrete lines
      are absent. A set of shifted emission lines was observed when diatom cultures
      reached adulthood. These discrete line shifts correlate with structural changes
      observed in adult frustules: reduction in pore diameter; appearance of pores
      within pores, 10 nm in size; an increase in the gap distance between stria; and
      the deposition of several girdle bands with a concomitant increase in the diatom
      waist length, as well as the appearance of pores on such bands. Destruction of
      the pores results in the disappearance of all discrete emission lines. The PL
      shifts are correlated with a substantial increment of Si-OH groups adsorbed on
      the frustule surface, as revealed by Fourier transform infrared spectroscopy.

PMID- 24585633
TI  - Uterine artery Doppler evaluation in twin pregnancies at 11 + 0 to 13 + 6 weeks
      of gestation.
AB  - OBJECTIVES: To compare uterine artery pulsatility index (PI) obtained at 11 + 0
      to 13 + 6 weeks of gestation in singleton and twin pregnancies and to evaluate
      changes in PI values of twin pregnancies developing pre-eclampsia (PE) or small
      for-gestational age (SGA) of either one or both fetuses. METHODS: Uterine artery
      PI was measured in 421 twin pregnancies (384 dichorionic and 37 monochorionic)
      and in 500 singleton pregnancies. The measured mean and lowest uterine artery PI
      values were converted to multiples of the expected normal median (MoM) after
      correction for maternal body mass index, ethnicity and gestational age. The
      median PI-MoM values of twins were compared with those of singleton pregnancies.
      In twin pregnancies, PI-MoM values were analyzed according to chorionicity,
      development of early-onset (< 34 weeks) or late-onset (>= 34 weeks) PE and SGA of
      one or both twins. RESULTS: Uterine artery PI-MoM was significantly lower in twin
      compared with singleton pregnancies (mean K = 174.31, P < 0.0001, lowest K =
      139.27, P < 0.0001). However, there were no significant differences in the
      uterine artery PI-MoM values between monochorionic and dichorionic twins. The
      uterine artery PI in twin pregnancies that developed early-onset PE (P < 0.001)
      and SGA of both twins (P < 0.05) was higher than the uterine artery PI in
      uncomplicated twin pregnancies, whereas no differences were found for late PE or
      SGA of one twin. CONCLUSIONS: First-trimester placental impedance to flow, as
      assessed by uterine artery Doppler examination, is reduced in twin pregnancies,
      with no differences related to chorionicity. The relative increase of uterine
      artery PI found in twin pregnancies that developed early PE and SGA of both twins
      suggests that first-trimester uterine artery assessment may be useful in
      identifying such complications.

PMID- 24585634
TI  - Imaging flow cytometry for automated detection of hypoxia-induced erythrocyte
      shape change in sickle cell disease.
AB  - In preclinical and early phase pharmacologic trials in sickle cell disease, the
      percentage of sickled erythrocytes after deoxygenation, an ex vivo functional
      sickling assay, has been used as a measure of a patient's disease outcome. We
      developed a new sickle imaging flow cytometry assay (SIFCA) and investigated its
      application. To perform the SIFCA, peripheral blood was diluted, deoxygenated (2%
      oxygen) for 2 hr, fixed, and analyzed using imaging flow cytometry. We developed
      a software algorithm that correctly classified investigator tagged "sickled" and
      "normal" erythrocyte morphology with a sensitivity of 100% and a specificity of
      99.1%. The percentage of sickled cells as measured by SIFCA correlated strongly
      with the percentage of sickle cell anemia blood in experimentally admixed samples
      (R = 0.98, P <= 0.001), negatively with fetal hemoglobin (HbF) levels (R = 
      0.558, P = 0.027), negatively with pH (R = -0.688, P = 0.026), negatively with
      pretreatment with the antisickling agent, Aes-103 (5-hydroxymethyl-2-furfural) (R
      = -0.766, P = 0.002), and positively with the presence of long intracellular
      fibers as visualized by transmission electron microscopy (R = 0.799, P = 0.002).
      This study shows proof of principle that the automated, operator-independent
      SIFCA is associated with predictable physiologic and clinical parameters and is
      altered by the putative antisickling agent, Aes-103. SIFCA is a new method that
      may be useful in sickle cell drug development.

PMID- 24585635
TI  - ERK3 promotes endothelial cell functions by upregulating SRC-3/SP1-mediated
      VEGFR2 expression.
AB  - Despite a regain of interest recently in ERK3 kinase signaling, the molecular
      regulations of both ERK3 gene expression and protein kinase activity are still
      largely unknown. While it is shown that disruption of ERK3 gene causes neonatal
      lethality, cell type-specific functions of ERK3 signaling remain to be explored.
      In this study, we report that ERK3 gene expression is upregulated by cytokines
      through c-Jun in endothelial cells; c-Jun binds to the ERK3 gene and regulates
      its transcription. We further reveal a new role for ERK3 in regulating
      endothelial cell migration, proliferation and tube formation by upregulating SRC
      3/SP-1-mediated VEGFR2 expression. The underlying molecular mechanism involves
      ERK3-stimulated formation of a transcriptional complex involving coactivator SRC
      3, transcription factor SP-1 and the secondary coactivator CBP. Taken together,
      our study identified a molecular regulatory mechanism of ERK3 gene expression and
      revealed a previously unknown role of ERK3 in regulating endothelial cell
      functions.

PMID- 24585636
TI  - Ultraspecific and highly sensitive nucleic acid detection by integrating a DNA
      catalytic network with a label-free microcavity.
AB  - Nucleic acid detection with label-free biosensors circumvents costly fluorophore
      functionalization steps associated with conventional assays by utilizing
      transducers of impressive ultimate detection limits. Despite this technological
      prowess, molecular recognition at a surface limits the biosensors' sensitivity,
      specificity, and reusability. It is therefore imperative to integrate novel
      molecular approaches with existing label-free transducers to overcome those
      limitations. Here, we demonstrate this concept by integrating a DNA strand
      displacement circuit with a micron-scale whispering gallery mode (WGM)
      microsphere biosensor. The integrated biosensor exhibits at least 25-fold
      improved nucleic acid sensitivity, and sets a new record for label-free
      microcavity biosensors by detecting 80 pM (32 fmol) of a 22nt oligomer; this
      improvement results from the catalytic behavior of the circuit. Furthermore, the
      integrated sensor exhibits extremely high specificity; single nucleotide variants
      yield 40- to 100-fold lower signal. Finally, the same physical sensor was
      demonstrated to alternatingly detect 2 different nucleic acid sequences through 5
      cycles of detection, showcasing both its reusability and its versatility. 

PMID- 24585637
TI  - CardiaMed mechanical valve: mid-term results of a multicenter clinical trial.
AB  - BACKGROUND: Prosthesis choice is a major concern in valvular surgery. METHODS: A
      multicenter clinical trial was performed to assess the efficacy and safety of the
      CardiaMed prosthetic heart valve. The study enrolled 420 patients who underwent
      mitral (209) or aortic (211) valve replacement from 2003 to 2004 at 7
      institutions in Russia, and who were followed up from 2006 to 2011. The mean age
      was 52.2 +/- 10.2 years (range, 12-78 years), 47.4% were female, and 99.05%
      completed the study. RESULTS: The maximum observation term was 7.5 years (2188.5
      patient-years); 1081.6 patient-years for aortic and 1106.9 patient-years for
      mitral valve replacement. The overall 7-year survival rate was 85.1%  +/- 3.7%;
      86.1%  +/- 4.8% and 84.4%  +/- 5.4% for aortic and mitral valve replacement,
      respectively. The 7-year freedom from valve-related death was 93.9%  +/- 3.7% and
      94.5%  +/- 3.2% for aortic and mitral valve replacement, respectively. When early
      mortality (<30 days) was excluded, these rates were 94.8%  +/- 3.1% and 93.8%  +/
      3.82%, respectively. Linearized valve-dependent complication rates were
      determined for structural valve failure (0%/patient-year overall), thrombosis
      (0.63%/patient-year, all for mitral valve replacement), thromboembolic
      complications including transient neurologic deficits (0.13%/patient-year
      overall, 0.5%/patient-year for aortic valve replacement, 0.8%/patient-year for
      mitral valve replacement), hemorrhagic bleeding (0.64%/patient-year overall,
      0.55%/patient-year for aortic valve replacement, 0.09%/patient-year for mitral
      valve replacement), prosthetic endocarditis (0.28%/patient-year overall,
      0.28%/patient-year for aortic valve replacement, 0%/patient-year for mitral valve
      replacement), and hemolysis (0%/patient-year overall). CONCLUSION: The CardiaMed
      mechanical heart valve prostheses meets world standards of safety and efficacy.

PMID- 24585638
TI  - Advantages of upper brachial artery cannulation in aortic surgery.
AB  - BACKGROUND: The best method of cerebral protection during aortic arch surgery
      remains controversial. However, antegrade cerebral perfusion seems to be the most
      favorable because of better neurological outcomes. Although there have been many
      studies on antegrade cerebral perfusion via upper brachial cannulation, there is
      a lack of studies focusing particularly on local complications, with objective
      findings. The aim of this study was to investigate the local neurological and
      vascular complications following upper brachial cannulation. METHODS AND RESULTS:
      This study included 44 patients who underwent procedures on the ascending aorta,
      aortic arch, or descending aorta with upper brachial artery cannulation for
      cardiopulmonary bypass at OSM Ortadogu Hospital and Cankaya Hospital between
      January 2009 and April 2012. The mean age of the 32 (72.7%) men and 12 (27.3%)
      women was 55.2 +/- 12.3 years. Doppler analysis of the upper brachial artery was
      performed in 26 (59%) patients. Mean follow-up time for Doppler analysis was 5.7
      +/- 2 months. The mean antegrade cerebral perfusion time was 35 +/- 16.1 min. The
      mean degree of hypothermia was 25.1 +/- 2.0 . Hospital death occurred in 4 (9.1%)
      patients, and 2 (4.5%) suffered local neurologic complications.
      Electromyelography analysis was carried out in the 2 patients who suffered local
      neurologic symptoms. CONCLUSIONS: Brachial artery cannulation is technically
      simple and less time consuming, thus suitable even for emergency cases. With an
      acceptable risk of local complications, we recommend routine use of upper
      brachial cannulation for antegrade cerebral perfusion.

PMID- 24585639
TI  - Novel emboli protection cannula during cardiac surgery: first animal study.
AB  - BACKGROUND: Stroke after open heart surgery is a major cause of morbidity and
      mortality. Up to 60% of intraoperative cerebral events are caused by emboli
      generated by manipulations of the aorta during surgery. This is the first animal
      study evaluating the safety and efficacy of a novel aortic cannula designed to
      extract solid and gaseous emboli during cardiac surgery. METHODS: Seven domestic
      pigs were connected to cardiopulmonary bypass using a CardioGard 24F aortic
      cannula. Three pigs that were cannulated with a standard aortic cannula were
      defined as controls. Several main flow and suction regimens were carried out.
      Osseous particles of different sizes were injected into the proximal aorta to
      simulate emboli. RESULTS: The CardioGard cannula demonstrated an overall emboli
      retrieval rate of 77%. A rate of 88.45% was demonstrated during the low-flow
      regimen used clinically during aortic manipulation. Gaseous and solid emboli were
      eliminated by suction, as demonstrated by epi-carotid ultrasound. No significant
      changes were observed in hemodynamic and laboratory parameters. CONCLUSIONS: The
      CardioGard cannula is as simple to use as a regular commercially available aortic
      cannula, having a similar safety profile and proven efficacy in capturing
      intraoperative emboli.

PMID- 24585640
TI  - Surgical off-pump closure of perimembranous ventricular septal defects.
AB  - OBJECTIVE: To present our first experience in perventricular closure of
      ventricular septal defect, which is in our opinion, an important adjunct to
      current ventricular septal defect treatment options. BACKGROUND: Surgical closure
      under cardiopulmonary bypass is the treatment of choice for a perimembranous
      ventricular septal defect. Percutaneous techniques have technical limitations. To
      date, an off-pump approach and device deployment through the wall of the right
      ventricle is not widespread and has only been reported from China and Germany. We
      think this approach is promising in selected patients. METHODS: In July 2012, 7
      pediatric patients with an isolated perimembranous ventricular septal defect (age
      range, 4 months to 8 years, mean 2.5 years, all female) with a body weight of 5
      to 27 kg, mean 12.7 kg, underwent minimally invasive perventricular device
      closure. RESULTS: In all patients, the ventricular septal defect was occluded
      successfully based on transesophageal echocardiographic confirmation. There were
      no cases of occluder dislocation noted in the operating room or in the
      postoperative period. No residual shunts were observed. There was no transient or
      persistent rhythm disorder in any of the patients. All patients were discharged 4
      5 days postoperatively, in excellent physical condition. CONCLUSIONS: The
      described off-pump approach showed excellent results. It offers such advantages
      as avoidance of the morbidity associated with cardiopulmonary bypass,
      significantly shorter hospital stay and therefore reduced costs, and a cosmetic
      advantage.

PMID- 24585641
TI  - Surgical stimulation of angiogenesis.
AB  - OBJECTIVE: The results of surgical approaches are unsatisfactory in patients with
      a distal arterial bed that is ineligible for revascularization. In this
      retrospective study, we investigated outcomes in patients who underwent surgical
      interventions that are reported to induce angiogenesis. METHOD: 6 patients
      diagnosed with thromboangiitis obliterans were included in this study. Of these 6
      patients, 2 underwent femoropopliteal bypass surgery using reversed great
      saphenous vein as a conduit. The other 4 underwent ascending venous
      arterialization (bypass from the popliteal artery to the great saphenous vein at
      the level of medial malleolus, using reversed great saphenous vein). RESULTS:
      During the early postoperative period, all of the reversed saphenous vein grafts
      were occluded. The mean postoperative ankle-brachial index increased from 0.33 to
      0.83. During the postoperative period, intermittent claudication disappeared in
      all patients. Angiograms taken during the postoperative period showed evidence of
      neovascularization when compared to those taken during preoperative evaluation.
      CONCLUSION: Wound healing is an inflammatory process that simultaneously
      activates angiogenesis. We propose that the improved ankle-brachial index values
      and neovascularization shown in our patients were associated with this
      inflammatory process.

PMID- 24585642
TI  - Changes of cardiac troponin I and operative mortality of coronary artery bypass.
AB  - BACKGROUND: Recently, cardiac troponin I has been used to detect myocardial
      injury because of its superior cardiac specificity. However, there has been
      debate about the appropriate timing and cutoff level of cardiac troponin I to
      detect perioperative myocardial injury after coronary artery bypass grafting. The
      objective of this study was to define the relationship between operative
      mortality and changes in cardiac troponin I after isolated coronary artery
      bypass. PATIENTS AND METHODS: A retrospective analysis was carried out on data of
      218 isolated coronary artery bypass patients who were operated on between June
      2009 and February 2012. All patients followed an institutional perioperative
      management protocol that included 6 cardiac troponin I measurements
      (preoperatively and 0, 12, 24, 36, and 48 h after coronary artery bypass).
      According to the patterns of cardiac troponin I, the patient cohort was divided
      into 2 groups. Group 1 was patients in whom cardiac troponin I levels decreased
      24 h after the operation, and group 2 comprised the patients with cardiac
      troponin I levels that did not decrease or even increased after 24 h. RESULTS:
      The operative mortality was 4.1% (9/218). Group 2 showed significantly higher
      mortality (5/25, 20%) than group 1 (4/193, 2.1%). CONCLUSION: An elevated cardiac
      troponin I level is common after coronary artery bypass. A persistently high
      level of cardiac troponin I after 24 h is an important predictor of operative
      mortality after coronary artery bypass surgery.

PMID- 24585643
TI  - Pulmonary thromboembolism in lung surgery: use of unfractionated heparin.
AB  - BACKGROUND: While thoracic surgeons occasionally encounter pulmonary
      thromboembolism, the use of unfractionated heparin may cause adverse effects.
      METHODS: We assessed a series of 323 consecutive pulmonary operations performed
      during 4 years from 2008 to 2011. All patients were given elastic stockings and
      intermittent pneumatic compression. During the first 2 years (2008-2009), none of
      the 169 patients received unfractionated heparin. In the second 2-year period
      (2010-2011), 135/154 patients received subcutaneous unfractionated heparin,
      either 5000 units (n = 37) or 2500 units (n = 93) twice daily for 3 days, or
      continuous intravenous unfractionated heparin (n = 5). The epidural catheters
      were withdrawn 6 h or more after unfractionated heparin use. Among patients
      without postoperative unfractionated heparin, 8 (42.1%) had a bleeding risk and 5
      (26.3%) had limited operative time. RESULTS: One (0.6%) patient developed
      pulmonary thromboembolism during 2008-2009, but none had this complication during
      2010-2011. The adverse outcome of intrathoracic bleeding occurred in one (2.7%)
      of the patients given 5000 units of unfractionated heparin, but no epidural
      hematomas occurred in these patients. CONCLUSION: Patients undergoing thoracic
      surgery at low risk of bleeding may receive unfractionated heparin to prevent
      pulmonary thromboembolism while avoiding epidural complications.

PMID- 24585645
TI  - Prognostic impact of vascular and lymphovascular invasion in early lung cancer.
AB  - BACKGROUND: The prognostic significance of vascular and lymphatic invasion in non
      small-cell lung cancer is under continuous debate. We analyzed the effect of
      tumor aggressiveness (lymphatic and/or vessel invasion) on survival and relapse
      in stage I and II non-small-cell lung cancer. METHODS: We retrospectively
      analyzed prospectively collected data of 457 patients with stage I and II non
      small-cell lung cancer from 1998 to 2008. Specimens were analyzed for
      intratumoral vascular invasion and lymphovascular space invasion. Overall
      survival and disease-free survival were estimated using the Kaplan-Meier method,
      and differences were determined by the logrank test. Cox regression analysis was
      performed to identify independent risk factors. RESULTS: The incidence of
      intratumoral vascular invasion was 23.4%, and this correlated significantly with
      grade of differentiation, visceral pleural involvement, lymphovascular space
      invasion, and N status. The incidence of lymphovascular space invasion was 5.5%,
      and this correlated significantly with grade of differentiation, lymph nodes
      involved, and intratumoral vascular invasion. On multivariate analyses,
      intratumoral vascular invasion proved to be an significant independent risk
      factor for overall survival but not for disease-free survival. Lymphovascular
      space invasion was associated significantly with early tumor recurrence but not
      with overall survival. CONCLUSIONS: Vascular and lymphatic invasion can serve as
      independent prognostic factors in completely resected non-small-cell lung cancer.
      Intratumoral vascular invasion and lymphovascular space invasion in early stage
      non-small-cell lung cancer are important factors in overall survival and early
      tumor recurrence. Further large scale studies with more recent patient cohorts
      and refined histological techniques are warranted.

PMID- 24585644
TI  - Pneumonectomy: risk factor or innocent bystander?
AB  - BACKGROUND: Pneumonectomy is associated with a higher operative mortality rate
      and worse 5-year survival after resection for non-small-cell lung cancer,
      compared to lobectomy. We investigated whether pneumonectomy is an independent
      risk factor for hospital mortality and poor long-term survival, after risk factor
      adjustment. METHODS: We analyzed a prospectively validated thoracic surgery
      database. Kaplan-Meier survival curves were constructed for patients who had
      undergone lobectomy (n = 1484) or pneumonectomy (n = 266). Logistic and Cox
      multivariate regression analysis and propensity matching were performed on
      hospital mortality and long-term survival data. RESULTS: Univariate analysis
      demonstrated that pneumonectomy was a significant risk factor for hospital death
      (p = 0.02) and long-term survival (p < 0.001). Logistic regression failed to
      demonstrate pneumonectomy as a risk factor for hospital mortality. Cox regression
      analysis failed to identify pneumonectomy as a statistically significant risk
      factor. Propensity analysis (n = 266 in each group with 1:1 matching)
      demonstrated that pneumonectomy was not associated with hospital mortality (p =
      0.37) or poorer long-term survival (p = 0.19) compared to lobectomy. CONCLUSION:
      Pneumonectomy is not an independent risk factor for hospital mortality or long
      term survival, after adjustment for confounding factors.

PMID- 24585646
TI  - Does cannabis smoking predispose to lung bulla formation?
AB  - OBJECTIVE: The data of a consecutive series of habitual marijuana smokers were
      retrospectively evaluated and compared with that of non-marijuana smokers to
      assess differences between the 2 groups. METHODS: 13 consecutive habitual
      marijuana smokers were referred for treatment of spontaneous pneumothorax. The
      demographic, clinical, radiological, and pathological findings of these patients
      were reviewed and compared with 140 non-marijuana smokers treated for the same
      pathology at the same time. RESULTS: Bullae were seen in 8/13 (62%) and 110/140
      (78%) of marijuana smokers and non-marijuana smokers, respectively. However, when
      patients less than 35-years old were considered, the incidence of bulla was
      higher in marijuana smokers than non-marijuana smokers (7/10 vs. 3/10, p < 0.05).
      The pathological findings showed a greater presence of inflammatory cells in
      specimens from marijuana smokers than those of non-marijuana smokers (8/11 vs.
      2/42, respectively, p < 0.05). No significant differences in hospital stay and
      clinical outcome were registered between the 2 groups. CONCLUSIONS: Despite the
      fact that we were unable to demonstrate that marijuana had a causal role in the
      development of emphysema, our study showed that marijuana smokers had a higher
      incidence of inflammatory cells in pathological specimens, which may favor lung
      injury, thus predisposing to bulla formation.

PMID- 24585647
TI  - Uniportal video-assisted thoracic surgery: the lesser invasive thoracic surgery.
AB  - OBJECTIVES: We evaluated whether single-port video-assisted thoracic surgery is
      feasible without compromising outcomes, and whether the technique could be
      reproduced by a trainee. METHODS: In a 6-month period, 37 operations were
      performed by single-port video-assisted thoracic surgery. Of the 37 patients, 27
      (73%) were male and the mean age was 45.1 +/- 21 years. Twenty-three (62%) were
      operated on by consultants and 14 (38%) by trainees. The procedures included 19
      (51.3%) operations for treatment of pneumothoraces, 8 (21.6%) metastasectomies, 7
      (18.9%) lung biopsies, 2 (5.4%) empyema debridements, and 1 (2.7%)
      pleuropericardial window. RESULTS: Mean operative time was 51.8 +/- 14.7 min.
      Patient-controlled analgesia infusion was used for 1.3 +/- 1 days. Three (8.1%)
      patients needed an operative reintervention, but there was no intensive treatment
      unit admission or hospital mortality. Mean postoperative hospital stay was 3.3 +/
      2.7 days. On follow-up, all patients had a tissue diagnosis and all lung nodules
      were R0 resections. Patients operated on by consultants and trainees had similar
      preoperative profiles and postoperative outcomes, except that those operated on
      by trainees used patient-controlled analgesia significantly longer (1.8 +/- 1.48
      vs. 1 +/- 0.48 days; p = 0.03). CONCLUSION: Single-port video-assisted thoracic
      surgery can be performed and reproduced well without compromising outcomes. It is
      considered aesthetically better and may reduce analgesic requirements, but it
      might not reduce hospital stay.

PMID- 24585648
TI  - Left ventricular hemangioma.
AB  - A young Saudi woman presented with symptoms of palpitation, near syncope,
      anxiety, and fatigue. Transthoracic echocardiography showed a left ventricular
      mass. Under cardiopulmonary bypass, brief cardioplegic arrest, and the aid of a
      thoracoscope, the mass was resected. Histologic examination showed a rare benign
      cardiac tumor: mixed cavernous-capillary hemangioma. 

PMID- 24585649
TI  - Progressive muscular dystrophy of heart: diagnosis easily missed by clinicians.
AB  - Muscular dystrophy connotes a heterogeneous group of inherited disorders
      characterized by progressive wasting and weakness of the skeletal muscles. In
      several forms of muscular dystrophy, cardiac dysfunction occurs, and cardiac
      disease may even be the predominant manifestation of the underlying genetic
      myopathy. We present a case of progressive muscular dystrophy of the heart in
      which the initial and only manifestation was sudden death in a young man. 

PMID- 24585650
TI  - Late atrial appendage perforation from a pacemaker lead pacemaker complication.
AB  - Lead perforation is a rare complication of device implantation, varying between
      0.3% and 1%, although the prevalence may be higher. Late lead perforations (>1
      month after implantation) are believed to be very rare. We describe the
      successful treatment of a 65-year-old man with late cardiac perforation due to
      the pacemaker active fixation lead after an uneventful implantation. 

PMID- 24585651
TI  - Recurrent left ventricular thrombus in Crohn's disease: a rare presentation.
AB  - A 40-year-old man with Crohn's disease was found to have recurrence of a large
      left ventricular mass on echocardiography during workup for stricturoplasty. He
      presented with left limb emboli. He had been diagnosed with a left ventricular
      thrombus 2 years earlier, with multiple cerebral and peripheral emboli, and
      underwent surgery. We carried out redo surgery, and histology revealed organized
      thrombus. We discuss the management of this complex case. 

PMID- 24585652
TI  - On-pump beating resection of cardiac pheochromocytoma.
AB  - We describe the case of 34-year-old woman with a cardiac pheochromocytoma that
      was diagnosed by scintigraphy using iodine-131 metaiodobenzylguanidine. For
      preoperative evaluation, we chose multidetector computed tomography instead of
      coronary angiography, for fear that catheter manipulation might trigger
      catecholamine release from the tumor; it showed that no major coronary artery
      branches run through the tumor. The tumor resection was carried out safely with
      the use of cardiopulmonary bypass and without cardiac arrest. 

PMID- 24585653
TI  - Pulmonary synovial sarcoma.
AB  - We describe the case of a 36-year-old man who presented with chest pain and a
      mass lesion occupying 2/3rds of the left hemithorax on a chest radiograph. A
      malignant pulmonary tumor was suspected, and after all diagnostic procedures,
      spindle-cell carcinoma was considered. Because of the proximity of the lesion to
      vascular structures, chemoradiotherapy was given before surgery. A left
      pneumonectomy was performed. Pathology identified a pulmonary synovial sarcoma
      which rarely occurs in the thorax. 

PMID- 24585654
TI  - Glomus tumor of the mediastinum.
AB  - Glomus tumors are rare benign myoepithelial neoplasms that can present with
      intractable pain. We report the case of a 59-year-old gentleman who presented
      with upper abdominal and chest pain caused by a posterior mediastinal glomus
      tumor arising from the spinal column, which required surgical resection. As
      glomus tumors usually develop in the limbs, this case highlights the complexity
      of diagnosis and treatment of glomus tumors when they present in rare locations. 

PMID- 24585655
TI  - Pancreaticopleural fistula: an overlooked entity.
AB  - Pleuropulmonary complications of pancreatitis are well known. Less commonly
      encountered is pancreaticopleural fistula. We describe the case of a 15-year-old
      boy with a presumed episode of pancreatitis, complicated by pseudocyst and
      development of a pancreaticopleural fistula. Successful medical management was
      achieved, and he made a full recovery. This case demonstrates that the rarity of
      such a condition leads to delay as well as challenges in diagnosis and
      management.

PMID- 24585656
TI  - Defeating the pores of Kohn.
AB  - In the treatment of emphysema with an endobronchial valve, entire lobar treatment
      is important in achieving adequate atelectasis. This case illustrates that
      without treatment of the entire lobe, it can fail to collapse even after several
      years, leading to treatment failure. Intralobar collateral ventilation through
      the pores of Kohn is demonstrated in this case, as endobronchial valve blockage
      of the remaining patent anterior segment resulted in the desired atelectasis and
      significant improvements in pulmonary function. 

PMID- 24585657
TI  - Unusual cystic lesions within pleural effusion.

PMID- 24585658
TI  - Huge glomus tumor of the lung.

PMID- 24585659
TI  - Dissection from ductus diverticulum presenting as type A intramural hematoma.

PMID- 24585660
TI  - Aneurysm of the anterior mitral valve leaflet.

PMID- 24585661
TI  - Atypical sternal cleft and clavicle agenesis.

PMID- 24585662
TI  - Robotic endovascular surgery.
AB  - The purpose of this review is to compare conventional endovascular procedures and
      the robotic endovascular approach in aortic aneurysm repair. Despite advantages
      over open surgery, conventional endovascular surgery has limitations. To develop
      an alternative, efforts have been focused on robotic endovascular systems. Two of
      the 3 studies comparing procedure times demonstrated reduced procedure time in
      the robotic group, by 6 times (p < 0.05). One study demonstrated that robotic
      procedures reduced fluoroscopic exposure time by 12 minute (p < 0.001). Three in
      vitro studies showed that the number of movements required in robotic surgery was
      reduced up to 10 times (p < 0.05). One of 2 studies measuring robotic performance
      score showed a better performance score in the robotic endovascular group (p =
      0.007). These results demonstrate that the robotic technique has multiple
      advantages over the conventional procedure, including improved catheter
      stability, a shorter learning curve, reduced procedure time, and better
      performance in cannulating tortuous vessels. However, robotic endovascular
      technology may be limited by the cost of the system, the size of the catheter,
      and the setup time required preoperatively. Further comparative studies between
      conventional and robotic approaches regarding cost-effectiveness, safety, and
      performance in cases involving complex anatomy and fenestrated stent grafts are
      essential. Nevertheless, this revolutionary technology is increasingly popular
      and may be the next milestone in endovascular surgery.

PMID- 24585663
TI  - Side-to-side anastomosis using 4 interrupted sutures in small coronary arteries.
AB  - Side-to-side anastomosis in sequential bypass grafting of coronary arteries 1.0
      mm in diameter or smaller, requires delicate surgical techniques with a high
      degree of technical difficulty. However, using only 4 interrupted sutures, we
      have performed side-to-side anastomosis in sequential grafting without difficulty
      in a short operative duration. We applied this technique in 58 distal anastomosis
      procedures, achieving an early angiographic graft patency rate of 100%.

PMID- 24585665
TI  - Concise review: the bone marrow niche as a target of graft versus host disease.
AB  - Graft versus host disease (GvHD) remains a major complication after allogeneic
      hematopoietic stem cell transplantation and is the main cause of transplant
      related mortality. In addition to visceral organ involvement, concomitant
      myelosuppression has been repeatedly described and the extent of cytopenia has
      been introduced into GvHD scoring systems. Both hematopoietic cells and cells
      that form the hematopoietic stem and progenitor cell niche have been identified
      as targets of GvHD. Although several contributing factors have been previously
      described, the pathophysiology of GvHD-mediated myelosuppression remains largely
      unclear and to date, no specific therapeutic interventions have achieved routine
      clinical application. This review focuses on the bone marrow as a target of GvHD,
      the factors that contribute to myelosuppression, and the possible therapeutic
      approaches.

PMID- 24585664
TI  - First evidence of pathology in the forelimb of the late Miocene saber-toothed
      felid Promegantereon ogygia (Machairodontinae, Smilodontini).
AB  - We examined the first evidence of pathology in the forelimb of the primitive
      saber-toothed felid Promegantereon ogygia, observed in a radius from the late
      Miocene (Vallesian, MN 10) site of La Roma 2 (Teruel, Spain). This fossil is the
      first evidence of a member of the Machairodontinae in this locality, and the
      first fossil of this species found in the Miocene basin of Teruel. The radius
      shows an exostosis shaped as a rough and wide bony crest probably caused by the
      lesion and posterior ossification of part of the tendon of the muscle abductor
      pollicis longus, an important extensor and abductor of the thumb. The lesion was
      probably due to a tearing or to high levels of exertion experienced by this
      muscle over a relatively long time, a general type of lesion also observed in
      other vertebrate fossils. With saber-toothed felids using their thumbs to
      immobilize prey during the hunt, the studied lesion probably affected in a
      significant manner the predatory abilities of the animal, causing at least a
      decrease in its hunting success rate.

PMID- 24585666
TI  - Work-related traumatic injuries onboard freezer-trawlers and freezer-longliners
      operating in Alaskan waters during 2001-2012.
AB  - BACKGROUND: Workers onboard freezer-trawl (FT) and freezer-longline (FL) vessels
      in Alaska may be at high risk for fatal and non-fatal injuries. METHODS:
      Traumatic occupational injuries onboard vessels in the FT and FL fleets were
      identified through two government data sources. RESULTS: The annual risk of fatal
      injuries was 125 per 100,000 FTEs in the FT fleet, and 63 per 100,000 FTEs in the
      FL fleet. The annual risk of non-fatal injuries was 43 per 1,000 FTEs in the FT
      fleet and 35 per 1,000 FTEs in the FL fleet. The majority of injuries in the FT
      fleet occurred in the factories and freezer holds, whereas the most common
      injuries in the FL fleet occurred on deck while working the fishing gear.
      CONCLUSIONS: The findings confirmed that workers in those fleets were at high
      risk for work-related injuries. Injury prevention should focus on removing
      hazards in the work processes injuring the most workers.

PMID- 24585667
TI  - First-trimester fetal cardiac examination using spatiotemporal image correlation,
      tomographic ultrasound and color Doppler imaging for the diagnosis of complex
      congenital heart disease in high-risk patients.
AB  - OBJECTIVE: A four-dimensional (4D) fetal echocardiographic technique utilizing
      spatiotemporal image correlation, tomographic ultrasound imaging display (STIC
      TUI echo) and color Doppler has previously been shown to be effective in
      displaying the examination planes constituting the extended cardiac examination.
      The aim of this study was to evaluate the performance of this first-trimester
      STIC-TUI echo technique in identifying complex congenital heart disease (CHD) in
      high-risk pregnancies. METHODS: This was a prospective study of patients
      presenting at first-trimester screening who were at high risk for CHD owing to
      pregestational diabetes, in-vitro fertilization (IVF), increased nuchal
      translucency (NT) thickness, first-trimester tricuspid regurgitation or reversed
      ductus venosus (DV) a-wave, a previous child with CHD or who were on
      anticonvulsant medication. First-trimester STIC-TUI echo was performed, and the
      findings were correlated with second-trimester echocardiography and post-delivery
      echo findings in survivors. RESULTS: One hundred and sixty-four fetuses from 152
      patients were enrolled (77 diabetics, 38 IVF, 14 with increased NT, 23 cases of
      tricuspid regurgitation or reversed a-wave in the DV, 22 with prior CHD and two
      on anticonvulsants). STIC-TUI echo was abnormal in 20 (12%), showing
      atrioventricular canal defect (n = 9), hypoplastic left heart (n = 2), pulmonary
      stenosis (n = 2), right aortic arch (n = 1), interrupted aortic arch (n = 1),
      tricuspid atresia (n = 1), heterotaxy (n = 1), persistent truncus arteriosus (n =
      1), double outlet right ventricle and ventricular septal defect (n = 1) and
      double inlet ventricle with transposition of the great arteries (n = 1). 85% of
      these anomalies were evident in the four-chamber view plane of the TUI display,
      and the remainder were diagnosed in the outflow tract planes with color Doppler
      imaging. In 13, CHD was isolated while seven had extracardiac anomalies. Thirteen
      fetuses had aneuploidy and all 13 underwent first-trimester termination of
      pregnancy. In the remaining seven, second-trimester echocardiography and neonatal
      echo/postmortem examination confirmed anomalies (two stillborn neonates, one
      neonatal death, four live births). Two cases of CHD missed by first-trimester
      STIC-TUI echo were diagnosed on second-trimester echo. Accordingly, first
      trimester STIC-TUI echo had 91% sensitivity and 100% specificity for the
      detection of CHD. CONCLUSIONS: First-trimester 4D echocardiography using a
      standardized application of STIC, TUI and color Doppler imaging is effective in
      displaying the imaging planes that are necessary for achieving the diagnosis of
      complex cardiac anomalies in high-risk patients. Optimal imaging of the four
      chamber view with two-dimensional ultrasound is the major determinant of
      successful volume acquisition.

PMID- 24585669
TI  - Transcription factors controlling development and function of innate lymphoid
      cells.
AB  - Innate lymphoid cells (ILCs) are a heterogeneous group of lymphocytes, which play
      an important role in tissue homeostasis at epithelial surfaces. They are scarce
      in spleen and lymph nodes, but substantial numbers can be found in the intestinal
      mucosa even at steady state. There, they represent the first line of defence
      against invading pathogens and contribute to lymphorganogenesis, tissue repair
      and, when inappropriately activated, immune pathology. Lineage-specific
      development, function and maintenance of these cells depend on a restricted set
      of transcription factors that partially emerged as a result of diversification
      and selection during vertebrate evolution. The differential expression of
      transcription factors regulates unique developmental programs, which endow the
      different ILC subsets with specific effector functions. Despite this division of
      labour, ILCs are considered to share a common origin, as they all are progeny of
      the common lymphoid progenitor, rely on the common gamma-chain (gammac) used by
      various cytokine receptors and show a developmental requirement for the
      transcriptional regulator Id2 (inhibitor of DNA binding 2). Here, we review the
      transcriptional programs required for the development and function of ILCs and
      give an overview of the evolution of transcription factors and cytokines
      expressed by ILCs. 

PMID- 24585673
TI  - Moneyball.

PMID- 24585674
TI  - Comparisons of retear patterns for 3 arthroscopic rotator cuff repair methods.
AB  - BACKGROUND: Only a few studies have reported an unusual retear pattern after
      arthroscopic rotator cuff repair based on the repair method. PURPOSE: To compare
      the retear pattern of the arthroscopic single-row technique (SRT), conventional
      suture-bridge technique (SBT), and knotless suture-bridge technique (K-SBT) for
      rotator cuff tears. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS:
      This study evaluated 65 shoulders with retears revealed on magnetic resonance
      imaging at least 6 months after arthroscopic repair for a full-thickness rotator
      cuff tear. A retear was revealed in 21, 22, and 22 shoulders after the SRT, SBT,
      and K-SBT, respectively. Retears were classified as type 1 (unhealed tendons),
      type 2 (medially ruptured tendons with a healed footprint), or type 3 (unable to
      classify). Retear patterns were classified as full- or partial-thickness lesions;
      partial-thickness retears were further classified as articular- or bursal-side
      lesions. RESULTS: A type 1 retear was observed in 71.4%, 40.9%, and 54.5% and a
      type 2 retear in 23.8%, 59.0%, and 40.9% of patients in the SRT, SBT, and K-SBT
      groups, respectively. No significant differences were observed among the 3 groups
      together (P = .195); however, a significant difference was observed between the
      SRT and SBT groups alone (P = .049). No significant differences were observed for
      either type 1 (P = .121) or type 2 (including both full- and partial-thickness)
      retears (P = .064) among the 3 groups together. When respective pairs of groups
      were compared, a significant difference was noted in both type 1 (P = .044) and
      type 2 retears (P = .019) between the SRT and SBT groups alone. No significant
      differences were observed in type 1 (P = .281) or type 2 full-thickness retears
      (P = .117) among the 3 groups together. When pairs of groups were compared, a
      significant difference in type 2 full-thickness retears was detected between the
      SRT and SBT groups alone (P = .037). CONCLUSION: The SBT has a different retear
      pattern than that of the SRT. However, the K-SBT retear pattern was not different
      from that of the SRT.

PMID- 24585675
TI  - Biomechanical consequences of a complete radial tear adjacent to the medial
      meniscus posterior root attachment site: in situ pull-out repair restores
      derangement of joint mechanics.
AB  - BACKGROUND: Complete radial tears near the medial meniscus posterior root
      attachment site disrupt the circumferential integrity of the meniscus (similar to
      a posterior root avulsion). These tears can compromise the circumferential
      integrity, and they have been reported in biomechanical studies to be comparable
      with the meniscectomized state. PURPOSE: To quantify the tibiofemoral contact
      pressure and contact area changes that occur in cadaveric knees from complete
      posterior horn radial tears and subsequent repairs of the medial meniscus
      adjacent to the posterior root attachment site. STUDY DESIGN: Controlled
      laboratory study. METHODS: Six nonpaired fresh-frozen human cadaveric knees each
      underwent 45 different testing conditions: 9 medial meniscus conditions (intact,
      root avulsion, root repair, serial radial tear at 3, 6, and 9 mm from the root
      attachment site, and in situ repair at the same 3 distances from the root
      attachment site) at 5 flexion angles (0 degrees , 30 degrees , 45 degrees , 60
      degrees , and 90 degrees ), under a 1000-N axial load. Tekscan sensors were used
      to measure contact area and pressure in the medial and lateral compartments.
      RESULTS: The medial meniscus root avulsion and all radial tear conditions
      resulted in significantly decreased contact area and increased mean contact
      pressure compared with the intact state for knee flexion angles beyond 0 degrees 
      (P < .05). The root repair and in situ repairs restored contact area and pressure
      to levels statistically indistinguishable from those of the intact meniscus and
      increased contact area and decreased contact pressure compared with the
      corresponding tear conditions. CONCLUSION: Posterior horn radial tears adjacent
      to the medial meniscus root that extend to the meniscocapsular junction can lead
      to derangement of the loading profiles of the medial compartment that are similar
      to a root avulsion. Repair of these radial tears with an in situ pull-out
      technique restored joint mechanics to the intact state. CLINICAL RELEVANCE:
      Complete radial tears of the posterior horn of the medial meniscus, which occur
      relatively frequently, are biomechanically equivalent to root avulsions and could
      potentially lead to medial compartment arthrosis. An in situ repair offers an
      alternative treatment to meniscectomy and can reestablish the posterior anchor
      point, thus improving load distribution in the medial compartment. Future
      clinical studies of these repairs are recommended.

PMID- 24585676
TI  - Do plant trichomes cause more harm than good to predatory insects?
AB  - Plants use trichomes as a morphological defense against attacks from herbivores.
      The literature was reviewed to test the hypothesis that trichome-bearing
      (pubescent) plants do not cause more harm than good to predators. Forty seven
      records on interactions between plant trichomes and predatory insects were found.
      Overall, the records reveal that trichomes have more harmful than beneficial
      effects on predators. Fortunately, most harmful effects are sublethal; they
      usually affect movement, development, oviposition and predation potential. In
      worst cases, sticky exudates from glandular trichomes entrap predators. The
      hooked tips on non-glandular trichomes impale predators. Entrapped and impaled
      predators often die from desiccation or starvation. Plant cultivars with high
      (rather than low) trichome density cause the most harm, and trichomes on tomato
      and some beans often cause more harm than good to predatory beetles, true bugs
      and lacewings. Whether these harmful effects have a net negative effect on plant
      fitness is poorly known and ripe for study. When developing and testing cultivars
      with increased trichome-based resistance to herbivory, the question as to whether
      these technologies are compatible with the functional role of those predators
      (single or combined species) capable of suppressing herbivore populations should
      be considered.

PMID- 24585677
TI  - Human skin-derived precursor cells are poorly immunogenic and modulate the
      allogeneic immune response.
AB  - Human skin-derived precursors (hSKPs) are multipotent somatic stem cells that
      persist within the dermis throughout adulthood and harbor potential clinical
      applicability. In this study, we investigated their immunogenicity and
      immunosuppressive features, both in vitro and in vivo. As such, this study
      provides a solid basis for developing their future clinical applications. We
      found that hSKPs express HLA-ABC molecules, but not HLA-DR, rendering them poorly
      immunogenic. Using a coculture set-up, we could further demonstrate that hSKPs
      inhibit the proliferation of allogeneic activated T cells and alter their
      cytokine secretion profile, in a dose-dependent manner. Cotransplantation of hSKP
      and human peripheral blood leukocytes (PBL) into severe combined immune-deficient
      mice also showed a significant impairment of the graft-versus-host response 1
      week post-transplantation and a drastic increase in survival time of 60%. From a
      mechanistic point of view, we found that hSKPs require cell contact as well as
      secretion of soluble inhibitory factors in order to modulate the immune response.
      The expression/secretion levels of these factors further increases upon
      inflammation or in the presence of activated T cells. As such, we believe that
      these features could be beneficial in a later allogeneic clinical setting,
      because rejection of engrafted allogeneic hSKP might be delayed or even avoided
      due to their own promotion of a tolerogenic microenvironment.

PMID- 24585678
TI  - Is lobar lung transplantation sufficient for patients with pokey thorax cavity?

PMID- 24585679
TI  - 18-Fluorine fluorodeoxyglucose positron emission tomography in the pretreatment
      evaluation of thymic epithelial neoplasms: a metabolic biopsy confirmed by Ki-67
      expression.
AB  - OBJECTIVES: To investigate the usefulness of 18-fluorine fluorodeoxyglucose
      ((18)F-FDG) positron emission tomography/computed tomography (PET-CT) in the
      pretreatment evaluation of thymic epithelial neoplasms (TENs). We previously
      demonstrated that the ratio between standardized uptake value of the tumour and
      aortic arch (SUV T/M) correlates with World Health Organization (WHO)
      classification. We now focused our evaluation on thymomas only, excluding
      carcinomas. We also searched for the expression of a pathological biomarker, Ki
      67, that gained both diagnostic and prognostic relevance for various solid
      tumours. Its correlation with SUV T/M and WHO classification was evaluated.
      METHODS: We performed a retrospective dynamic cohort study of data from January
      2006 to December 2012, on 23 consecutive patients with pathologically proven TEN,
      excluding thymic carcinomas, evaluated with PET-CT. For each patient, SUV T/M was
      calculated. The patients were then categorized, according to WHO classification,
      into two groups (low-risk: 3 A, 9 AB, 5 B1; high-risk: 5 B2, 1 B3) and Ki-67
      labelling index (LI) was defined. We employed the Spearman rank non-linear
      correlation coefficient (rho) to estimate the correlations between variables.
      RESULTS: SUV T/M proved to be significantly higher for high-positive Ki-67
      samples, indicating a strong correlation between SUV T/M and Ki-67 LI (rho =
      0.8). Furthermore, high Ki-67 LI samples correlate with the higher-risk WHO
      subgroup (rho = 0.9). CONCLUSIONS: FDG PET-CT can provide a useful tool in the
      preoperative work-up of TEN, reflecting its proliferation capacity, as described
      also by the Ki-67 expression. In particular, SUV T/M could provide a 'metabolic
      biopsy' to divide TEN into high-risk and low-risk neoplasms.

PMID- 24585680
TI  - After-hours coverage of cardiothoracic critical care units by non-surgeons:
      process and value issues.

PMID- 24585681
TI  - Omentoplasty is effective in preventing anastomotic leakage of
      oesophagogastrostomy following radical oesophagectomy and reducing the mortality
      during the anastomotic leakage.

PMID- 24585682
TI  - Automated fabrication of 2-nm solid-state nanopores for nucleic acid analysis.
AB  - We demonstrate the automated and reproducible fabrication of sub-2-nm nanopores
      in 10-nm thick silicon nitride membranes, through controlled dielectric breakdown
      in solution. Our results reveal that under the appropriate conditions, nanopores
      can be fabricated with a size no larger than 2.0 +/- 0.5-nm in diameter for a
      sample of N = 23 nanopores, with an average and standard deviation of 1.3 +/- 0.6
      nm. The dimensions of these nanopores are confirmed by using individual
      translocating DNA molecules as molecular rulers. We show that a 2.0-nm and a 2.1
      nm diameter nanopore are capable of distinguishing single-stranded DNA versus
      double-stranded DNA, and that a 2.4-nm diameter nanopore can be used to
      investigate the overstretching transition in short dsDNA fragments. These results
      highlight the reliability and precision of the automated fabrication of nanopores
      via controlled dielectric breakdown, showing great promise for the manufacturing
      of future nanopore-based technologies. 

PMID- 24585683
TI  - FLRT2 interacts with fibronectin in the ATDC5 chondroprogenitor cells.
AB  - Expression studies have implicated FLRT2 in cranial neural crest cell migration
      and prechondrogenic cell condensation during craniofacial skeletogenesis. We
      aimed to determine whether FLRT2 was involved in mediating cell-matrix
      interactions in the ATDC5 chondroprogenitor cell line. Immunolocalization
      experiments of ATDC5 cells revealed that FLRT2 was present on the cell membrane
      as well as extracellularly, where it colocalized with Fibronectin (Fn). After
      cell extraction of the matrix, FLRT2 was identified in the ATDC5-derived
      extracellular matrix (ECM) and was further found to be associated with Fn-coated
      beads in cell cultures. Blockage of Fn fibril formation via a blocking peptide
      resulted in a concomitant decrease in extracellular FLRT2 accumulation. Over a 7
      day period following the replenishment of the Fn blocking peptide to the
      cultures, there was a partial rebound in Fn fibril formation that was accompanied
      by a concomitant reappearance of FLRT2 co-expression. Co-immunoprecipitation
      confirmed that FLRT2 and Fn interacted, either directly or indirectly.
      Immunoprecipitation and Western blot analyses with antibodies recognizing
      epitopes located on the extra- and intracellular domains of FLRT2 further
      revealed the presence of different sized bands, suggesting that FLRT2 may exist
      in both membrane-bound and shed forms. Our data therefore provide evidence that
      FLRT2 and/or its cleavage products may be cooperating with Fn and other ECM
      proteins to regulate critical cellular events. Further studies will be necessary
      in delineate more precisely the roles of FLRT2 in mediating cell- and cell-matrix
      interactions during normal development.

PMID- 24585685
TI  - Clinical characteristics of monochorionic twins with large hemoglobin level
      discordance at birth.
AB  - OBJECTIVES: To evaluate neonatal outcomes and clinical characteristics of
      monochorionic diamniotic (MCDA) twins with a large intertwin hemoglobin (Hb)
      difference at birth. METHODS: This was a retrospective cohort study of MCDA twin
      gestations delivered at Osaka Medical Center and Research Institute for Maternal
      and Child Health between 2003 and 2012. Cases of pregnancy termination, acardiac
      twins or intrauterine death were excluded. A large intertwin Hb difference at
      birth was defined as > 8.0 g/dL according to the postnatal criteria for twin
      anemia-polycythemia sequence (TAPS). The intertwin reticulocyte count ratio (RCR)
      was calculated by dividing the reticulocyte count of the anemic twin by that of
      the polycythemic twin. Cases with Hb differences were divided into two groups
      according to the RCR, TAPS when the RCR was > 1.7 and acute fetofetal hemorrhage
      (AFFH) when the RCR was <= 1.7. Neonatal outcomes were compared between the TAPS
      and AFFH groups. RESULTS: During the study period, 432 MCDA twin pregnancies of a
      total of 532 born at our hospital were analyzed. There were 12 (2.8%) cases of a
      large intertwin Hb difference. The median gestational age at birth of these cases
      was 34 (range, 23-38) weeks, and all were delivered by Cesarean section. There
      were seven (1.6%) cases of TAPS and five (1.2%) of AFFH. The neonatal survival
      rate was 91.7%; in one pair of twins with TAPS neonatal death occurred. All
      (100%) cases with TAPS and two (40%) with AFFH required blood transfusion or
      partial-exchange transfusion for at least one infant. CONCLUSIONS: Although the
      incidence of TAPS and AFFH may be low in MCDA twins, many affected neonates
      required treatment for hematological abnormalities. Delivery of MCDA twins via
      Cesarean section does not appear to prevent AFFH, despite the absence of labor.

PMID- 24585686
TI  - Assessment of the rate of force development scaling factor for the hip muscles.
AB  - INTRODUCTION: The aim of this study was to evaluate test feasibility, validity,
      and reproducibility of the rate of force development scaling factor (RFD-SF) for
      the hip muscles. METHODS: Feasibility was assessed as the testing compliance,
      validity as the ability to compute the RFD-SF from a linear regression, and
      reproducibility with a test-retest design in 20 healthy subjects. Reliability and
      agreement (reproducibility) were evaluated using intraclass correlation
      coefficient (ICC3,1) and percent standard error of measurement (SEM),
      respectively. RESULTS: The RFD-SF testing protocol was completed successfully by
      all subjects, although the analysis had to be modified for hip rotators.
      Reliability was high (ICC3,1 > 0.70) for all muscles except hip abductors (ICC3,1
      = 0.69) and internal rotators (ICC3,1 = 0.58). Agreement was high for all muscles
      (SEM < 10%). CONCLUSIONS: Hip adductor, flexor, and external rotator RFD-SF can
      be evaluated with confidence, provided the analysis is modified for external
      rotators, whereas hip abductor and internal rotator RFD-SF assessment is not
      recommended.

PMID- 24585687
TI  - Simplified first-trimester fetal cardiac screening (four chamber view and
      ventricular outflow tracts) in a low-risk population.
AB  - OBJECTIVES: Our aim was to assess the accuracy of a simplified fetal cardiac
      study, inclusive of four-chamber view (4CV) and ventricular outflow tracts,
      performed during the 11-14 week screening by well-trained obstetricians to detect
      congenital heart diseases (CHDs). METHODS: A transabdominal ultrasound was
      performed on 4820 singleton pregnant women at 11-14 weeks to visualize the
      visceral site, the 4CV, and the outflow tracts. Neonatal outcomes were recorded 6
      and 12 months after birth. RESULTS: Among the 4820 patients reviewed, 790 were
      excluded because of loss at prenatal or postnatal follow-up (649 cases), or
      inability to obtain adequate first-trimester sonographic cardiac evaluation (141
      cases). Among the 4030 included cases, 32 CHD cases were detected (20 major and
      12 minor); 18 of the major (90%) and five of the minor (42%) were detected or
      suspected in the first trimester, one major and six minor in the second
      trimester, and one major and one minor only after birth. CONCLUSIONS: A
      simplified protocol is an effective tool to screen for CHD at 11-14 weeks.

PMID- 24585689
TI  - Herbicide resistance modelling: past, present and future.
AB  - Computer simulation modelling is an essential aid in building an integrated
      understanding of how different factors interact to affect the evolutionary and
      population dynamics of herbicide resistance, and thus in helping to predict and
      manage how agricultural systems will be affected. In this review, we first
      discuss why computer simulation modelling is such an important tool and framework
      for dealing with herbicide resistance. We then explain what questions related to
      herbicide resistance have been addressed to date using simulation modelling, and
      discuss the modelling approaches that have been used, focusing first on the
      earlier, more general approaches, and then on some newer, more innovative
      approaches. We then consider how these approaches could be further developed in
      the future, by drawing on modelling techniques that are already employed in other
      areas, such as individual-based and spatially explicit modelling approaches, as
      well as the possibility of better representing genetics, competition and
      economics, and finally the questions and issues of importance to herbicide
      resistance research and management that could be addressed using these new
      approaches are discussed. We conclude that it is necessary to proceed with
      caution when increasing the complexity of models by adding new details, but, with
      appropriate care, more detailed models will make it possible to integrate more
      current knowledge in order better to understand, predict and ultimately manage
      the evolution of herbicide resistance.

PMID- 24585690
TI  - Biomolecule-doped PEDOT with three-dimensional nanostructures as efficient
      catalyst for oxygen reduction reaction.
AB  - Metal macro-cyclic compounds have drawn considerable attention as alternative
      catalysts for oxygen reduction reaction. However, the continuous pyrolysis
      process usually needed for improving the performance of these compounds require
      an elevated temperature and complicated procedures, thus leading to an
      unpredictable transformation of the chemical structures and limiting their
      applications. Herein, we develop a new insight to fabricating hemin-doped poly
      (3,4-ethylenedioxythiophene) (PEDOT) with controllable three-dimensional
      nanostructures via a one-step, tri-phase, self-assembled polymerization routine.
      We demonstrate that the hemin-induced synergistic effect results in a very high 4
      electron oxygen reduction activity, a better stability, and free from methanol
      crossover effects even in a neutral phosphate buffer solution (PBS). 

PMID- 24585688
TI  - Hhex and Cer1 mediate the Sox17 pathway for cardiac mesoderm formation in
      embryonic stem cells.
AB  - Cardiac muscle differentiation in vivo is guided by sequential growth factor
      signals, including endoderm-derived diffusible factors, impinging on cardiogenic
      genes in the developing mesoderm. Previously, by RNA interference in AB2.2 mouse
      embryonic stem cells (mESCs), we identified the endodermal transcription factor
      Sox17 as essential for Mesp1 induction in primitive mesoderm and subsequent
      cardiac muscle differentiation. However, downstream effectors of Sox17 remained
      to be proven functionally. In this study, we used genome-wide profiling of Sox17
      dependent genes in AB2.2 cells, RNA interference, chromatin immunoprecipitation,
      and luciferase reporter genes to dissect this pathway. Sox17 was required not
      only for Hhex (a second endodermal transcription factor) but also for Cer1, a
      growth factor inhibitor from endoderm that, like Hhex, controls mesoderm
      patterning in Xenopus toward a cardiac fate. Suppressing Hhex or Cer1 blocked
      cardiac myogenesis, although at a later stage than induction of Mesp1/2. Hhex was
      required but not sufficient for Cer1 expression. Over-expression of Sox17 induced
      endogenous Cer1 and sequence-specific transcription of a Cer1 reporter gene.
      Forced expression of Cer1 was sufficient to rescue cardiac differentiation in
      Hhex-deficient cells. Thus, Hhex and Cer1 are indispensable components of the
      Sox17 pathway for cardiopoiesis in mESCs, acting at a stage downstream from
      Mesp1/2.

PMID- 24585691
TI  - Natural course of rotator cuff syndrome in a French working population.
AB  - BACKGROUND: The aim was to assess the persistence of rotator cuff syndrome (RCS)
      in workers and to study associations with personal and work-related factors, job
      change, exposure change and treatment. METHODS: At baseline, 274 workers suffered
      from RCS, of whom 150 were followed up. Three groups were constituted: (1) a RCS
      recovery group, (2) a shoulder pain without RCS group, and (3) a RCS without
      recovery group. We studied the differences between groups (1) and (3) because of
      the low number of workers in group (2). RESULTS: Recovery occurred in 61.5% of
      men and 51.4% of women. Factors related to work were associated with persistence
      of RCS in men whereas upper limb pain and absence of job rotation were associated
      with persistence of RCS in women. CONCLUSION: This descriptive study showed that
      a high percentage of workers recovered and several personal and work-related
      factors were associated with persistent RCS. Larger prospective studies are
      needed to confirm these results.

PMID- 24585692
TI  - Integrated non-invasive imaging of acute ST-elevation myocardial infarction
      without obstructive coronary artery disease.

PMID- 24585693
TI  - An investigation of the biosocial model of borderline personality disorder.
AB  - OBJECTIVES: We sought to test the Biosocial Theory of borderline personality
      disorder (BPD) that posits that borderline traits are due to emotional
      dysregulation, caused by the interaction between childhood emotional
      vulnerability and invaliding parenting. METHOD: A total of 250 adults (76%
      female, median age = 32.06 years) from a nonclinical population completed self
      report measures assessing current levels of borderline traits and emotional
      dysregulation. They also completed retrospective measures of childhood emotional
      vulnerability and parental invalidation. RESULTS: Invalidating parenting and
      emotional vulnerability independently predicted emotion dysregulation, but an
      interaction effect was not found. Having experienced validating parenting was
      found to be a protective factor for developing borderline traits but was not
      significantly related to emotional dysregulation. CONCLUSION: Data in this sample
      did not support the underlying genesis of BPD proposed by the Biosocial Theory
      and a model that more parsimoniously explains the development of BPD is proposed.

PMID- 24585694
TI  - Doppler echocardiographic isovolumetric time intervals in diagnosis of fetal
      blocked atrial bigeminy and 2:1 atrioventricular block.
AB  - OBJECTIVE: To distinguish between blocked atrial bigeminy (BB) and incomplete
      atrioventricular block with 2:1 conduction (2:1 AVB) can be very difficult,
      especially in the mid-term fetus. Making a correct diagnosis has important
      clinical implications, as their prognosis and management differ markedly. Our
      objective was to investigate whether analysis of isovolumetric time intervals
      could improve Doppler echocardiography in differentiating these conditions.
      METHODS: Sixteen fetuses with sustained BB or isolated 2:1 AVB, diagnosed at our
      tertiary center from 2002 to 2012, were reviewed retrospectively. Doppler
      recordings of left ventricular in- and outflow, including mitral and aortic valve
      movements, were used to measure isovolumetric contraction (ICT) and relaxation
      (IRT) time intervals. ICT reference values obtained from 104 normal pregnancies
      were used for comparison. RESULTS: Ten fetuses had BB and six 2:1 AVB. Five of
      the AVB cases were anti-Ro antibody positive and one had long QT syndrome (LQTS).
      ICT was systematically shorter in BB than in antibody-mediated 2:1 AVB. Nine of
      10 cases with BB had an ICT below -2 SD and the five with antibody-mediated 2:1
      AVB had values at or above +2 SD. All 15 fetuses with either BB or antibody
      mediated AVB had an IRT of < 70 ms, as opposed to a markedly prolonged IRT (105
      ms) in the LQTS case. CONCLUSION: Measurement of ICT can improve the differential
      diagnosis between BB and antibody-mediated 2:1 AVB. Fetuses with BB or antibody
      mediated AVB are unlikely to have IRT measurements exceeding 70 ms and, when this
      is observed, LQTS should be considered a more likely diagnosis.

PMID- 24585695
TI  - The glucosaminidase domain of Atl - the major Staphylococcus aureus autolysin -
      has DNA-binding activity.
AB  - In this communication, we describe evidence demonstrating the capacity of Atl,
      the major Staphylococcus aureus autolytic enzyme to bind DNA. Electrophoretic
      mobility shift assays (EMSA) show that both the Atl protein and the endo-beta-N
      acetylglucosaminidase (GL) domain were able to bind DNA of nonspecific sequence.
      The implications of this unexpected observation for the physiology of S. aureus
      remain to be explored. 

PMID- 24585696
TI  - Eda/Edar signaling guides fin ray formation with preceding osteoblast
      differentiation, as revealed by analyses of the medaka all-fin less mutant afl.
AB  - BACKGROUND: Ectodysplasin (Eda) signaling is essential for the morphogenesis of
      several ectodermal appendages. RESULTS: Here, we report a medaka mutant, all-fin
      less (afl), which has a nonsense mutation in its eda gene. The adult afl fish
      displayed various abnormalities of its dermal skeleton, such as short and twisted
      fin rays, missing and abnormally shaped scales and teeth, and skull deformation.
      Focusing on the developing fin rays in the caudal region of afl larvae, we found
      that the fin rays did not elongate; although the initial formation of fin rays
      proceeded normally. Additionally, eda expression was lost, and the expression
      pattern of edar, the gene for the receptor of Eda, was different from wild-type
      one. In vivo imaging of the double-transgenic medaka expressing enhanced green
      fluorescent protein under control of the edar promoter and DsRed under control of
      the osterix promoter revealed that edar expression preceded that of osterix and
      that the edar-expressing cells migrated in the direction of fin ray elongation,
      indicating that the Eda/Edar signaling event precedes osteoblast differentiation.
      CONCLUSIONS: Our findings provide evidence that Eda signaling accompanied with
      the binding of Eda to Edar are essential for fin ray formation guided by cell
      migration.

PMID- 24585697
TI  - Reply to Tardieu et al.

PMID- 24585699
TI  - Case definition of encephalitis may misdiagnose congenital urea cycle disorders.

PMID- 24585700
TI  - Distribution of prothioconazole and tebuconazole between wheat ears and flag
      leaves following fungicide spraying with different nozzle types at flowering.
AB  - BACKGROUND: Wheat ears are difficult targets from the aspect of fungicide
      spraying. Sideward-spraying nozzle types may enhance the ear coverage, which may
      possibly lead to higher effectiveness in the management of Fusarium head blight
      (FHB). RESULTS: On average, sideward-spraying Turbo TeeJet Duo nozzles resulted
      in 1.30 and 1.43 times higher prothioconazole-desthio and tebuconazole contents
      and Turbo FloodJet nozzles in 1.08 and 1.34 times higher prothioconazole-desthio
      and tebuconazole contents in wheat ears by comparison with those achieved with
      vertically-spraying XR TeeJet nozzles. In contrast, the vertically-spraying XR
      TeeJet nozzles resulted in 1.57 and 1.31 times higher prothioconazole-desthio and
      tebuconazole contents in the flag leaf blade. The degradation of the active
      ingredient (AI) depended on the year, the cultivar and the plant organ, but not
      on the spraying method. There was no clear relationship between the efficacy of a
      given nozzle type and the outcome of the FHB epidemic. CONCLUSIONS: The ear
      coverage and therefore the AI content have been improved with the two sideward
      spraying nozzle types. There was no effective translocation of the AI content
      between the ears and flag leaf blades. Prothioconazole and tebuconazole proved to
      be highly effective in the management of FHB, but the FHB resistance of the
      cultivar was also decisive.

PMID- 24585702
TI  - 2013 Annual Meeting of the American Society for Bone and Mineral Research,
      October 4-7, 2013, Baltimore, MD.

PMID- 24585701
TI  - Self-monitoring of spontaneous physical activity and sedentary behavior to
      prevent weight regain in older adults.
AB  - OBJECTIVE: The objective was to determine whether adding a self-regulatory
      intervention (SRI) focused on self-monitoring of spontaneous physical activity
      (SPA) and sedentary behavior to a standard weight loss intervention improved
      maintenance of lost weight. METHODS: Older (65-79 years), obese (BMI = 30-40
      kg/m(2) ) adults (n = 48) were randomized to a 5-month weight loss intervention
      involving a hypocaloric diet (DIET) and aerobic exercise (EX) with or without the
      SRI to promote SPA and decrease sedentary behavior (SRI + DIET + EX compared with
      DIET + EX). Following the weight loss phase, both groups transitioned to self
      selected diet and exercise behavior during a 5-month follow-up. Throughout the 10
      months, the SRI + DIET + EX group utilized real-time accelerometer feedback for
      self-monitoring. RESULTS: There was an overall group by time effect of the SRI (P
      < 0.01); DIET + EX lost less weight and regained more weight than SRI + DIET +
      EX. The average weight regain during follow-up was 1.3 kg less in the SRI + DIET
      + EX group. Individuals in this group maintained approximately 10% lower weight
      than baseline compared with those in the DIET + EX group whom maintained
      approximately 5% lower weight than baseline. CONCLUSIONS: Addition of a SRI,
      designed to increase SPA and decrease sedentary behavior, to a standard weight
      loss intervention enhanced successful maintenance of lost weight.

PMID- 24585703
TI  - A localized ELF magnetic field exposure system for microscope cover-slips.
AB  - In extremely low frequency (ELF) magnetic field exposure systems for the inverted
      microscope stage where the cells grown on the entire microscope cover-slip are
      exposed to the magnetic field, the effects of variations in cell characteristics
      from one cover-slip to another on the experimental data cannot be readily
      identified. To overcome this drawback, a localized ELF magnetic field exposure
      system for cells grown on cover-slips was designed. The basic idea is to expose
      only a marked portion of the cover-slip to the magnetic field so that the effect
      of the ELF magnetic field on the cells grown on the same cover-slip can be
      observed under a microscope. A prototype system was built and tested.
      Experimental test results pertaining to the prototype system performance validate
      the proposed design approach. The paper concludes with a discussion of
      alternative approaches to the design of localized ELF magnetic field exposure
      systems.

PMID- 24585704
TI  - Concise review: The role of C-kit expressing cells in heart repair at the
      neonatal and adult stage.
AB  - Ischemic heart disease is the number one cause of morbidity and mortality in the
      developed world due to the inability of the heart to replace lost myocytes. The
      cause of postinfarction myogenic failure has been a subject of intense scientific
      investigation and much controversy. Recent data indicate a brief perinatal
      developmental window exists during which postinfarction myogenesis, and
      substantial heart regeneration, occurs. By contrast, repair of an equivalent
      injury of the adult heart results in prominent revascularization without
      myogenesis. Here, we review recent experiments on neonatal postinjury myogenesis,
      examine the mechanistic hypotheses of dedifferentiation and precursor expansion,
      and discuss experiments indicating that postinfarction revascularization derives
      primarily from cardiac vascular precursors. These data have profound consequences
      for the understanding of human heart repair, as they address the long standing
      question as to whether human postinfarction myogenic failure is due to the loss
      of precursors existent at the neonatal stage or to a context-dependent inhibition
      of these precursors within the infarct, and suggest strategies for the
      recapitulation of neonatal myogenic capacity and the augmentation of
      revascularization.

PMID- 24585705
TI  - Positive interaction between prebiotics and thiazolidinedione treatment on
      adiposity in diet-induced obese mice.
AB  - OBJECTIVES: To investigate whether inulin-type fructan (ITF) prebiotics could
      counteract the thiazolidinedione (TZD, PPARgamma activator) induced-fat mass
      gain, without affecting its beneficial effect on glucose homeostasis, in high-fat
      (HF) diet fed mice. METHODS: Male C57bl6/J mice were fed a HF diet alone or
      supplemented with ITF prebiotics (0.2 g/day * mouse) or TZD (30 mg pioglitazone
      (PIO)/kg body weight * day) or both during 4 weeks. An insulin tolerance test was
      performed after 3 weeks of treatment. RESULTS: As expected, PIO improved glucose
      homeostasis and increased adiponectinaemia. Furthermore, it induced an over
      expression of several PPARgamma target genes in white adipose tissues. ITF
      prebiotics modulated the PIO-induced PPARgamma activation in a tissue-dependent
      manner. The co-treatment with ITF prebiotics and PIO maintained the beneficial
      impact of TZD on glucose homeostasis and adiponectinaemia. Moreover, the
      combination of both treatments reduced fat mass accumulation, circulating lipids
      and hepatic triglyceride content, suggesting an overall improvement of
      metabolism. Finally, the co-treatment favored induction of white-to-brown fat
      conversion in subcutaneous adipose tissue, thereby leading to the development of
      brite adipocytes that could increase the oxidative capacity of the tissue.
      CONCLUSIONS: ITF prebiotics decrease adiposity and improve the metabolic response
      in HF fed mice treated with TZD.

PMID- 24585698
TI  - Illness in travelers returned from Brazil: the GeoSentinel experience and
      implications for the 2014 FIFA World Cup and the 2016 Summer Olympics.
AB  - BACKGROUND: Brazil will host the 2014 FIFA World Cup and the 2016 Olympic and
      Paralympic Games, events that are expected to attract hundreds of thousands of
      international travelers. Travelers to Brazil will encounter locally endemic
      infections as well as mass event-specific risks. METHODS: We describe 1586 ill
      returned travelers who had visited Brazil and were seen at a GeoSentinel Clinic
      from July 1997 through May 2013. RESULTS: The most common travel-related
      illnesses were dermatologic conditions (40%), diarrheal syndromes (25%), and
      febrile systemic illness (19%). The most common specific dermatologic diagnoses
      were cutaneous larva migrans, myiasis, and tungiasis. Dengue and malaria,
      predominantly Plasmodium vivax, were the most frequently identified specific
      causes of fever and the most common reasons for hospitalization after travel.
      Dengue fever diagnoses displayed marked seasonality, although cases were seen
      throughout the year. Among the 28 ill returned travelers with human
      immunodeficiency virus (HIV) infection, 11 had newly diagnosed asymptomatic
      infection and 9 had acute symptomatic HIV. CONCLUSIONS: Our analysis primarily
      identified infectious diseases among travelers to Brazil. Knowledge of illness in
      travelers returning from Brazil can assist clinicians to advise prospective
      travelers and guide pretravel preparation, including itinerary-tailored advice,
      vaccines, and chemoprophylaxis; it can also help to focus posttravel evaluation
      of ill returned travelers. Travelers planning to attend mass events will
      encounter other risks that are not captured in our surveillance network.

PMID- 24585706
TI  - Profiling left and right ventricular proportional output during fetal life with a
      novel systolic index in the aortic isthmus.
AB  - OBJECTIVE: Left ventricular ejection causes forward flow in the fetal aortic
      isthmus while the right ventricle has a retrograde influence. The aim of this
      study was to create reference values for an isthmic systolic index (ISI)
      reflecting the changing influence of right and left ventricular performance on
      Doppler flow velocity waveforms of the aortic isthmus throughout normal
      pregnancy. METHODS: Doppler recordings of 260 normal fetuses with a gestational
      age of 18-37 weeks were reviewed. Peak systolic velocity (PSV) and end-systolic
      velocity (or systolic nadir; Ns) were measured on all aortic isthmus waveforms.
      An ISI was derived from the ratio Ns/PSV. Left and right ventricular outputs were
      also calculated. RESULTS: Up to 22-23 weeks' gestation, the mean ISI is stable at
      around 0.2. At about 28 weeks, a brief end-systolic deceleration wave is observed
      on the aortic isthmus waveforms, progressing steadily with gestation and causing
      a fall of ISI towards a mean value of zero between 30 and 31 weeks. This trend
      continues thereafter and a mean value of -0.4 was observed at the end of
      pregnancy. An inverse correlation was found between right ventricular output and
      Ns (r = -0.334, P = 0.001). Simultaneous recordings of the isthmus and the ductus
      arteriosus Doppler waveforms demonstrated that the primary cause of the end
      systolic deceleration and ultimate reversal of flow at the isthmus is the
      increasingly dominant flow from the right ventricle. CONCLUSION: The transitional
      changes of the respective right and left ventricular outputs throughout pregnancy
      are well profiled by the ISI. This index highlights the physiological increase in
      fetal right ventricle flow preponderance as pregnancy progresses. Alteration of
      the ISI profile could be expected in clinical conditions associated with
      unbalanced alteration of the fetal ventricular outputs.

PMID- 24585708
TI  - Sarcopenic obesity and dynapenic obesity: 5-year associations with falls risk in
      middle-aged and older adults.
AB  - OBJECTIVES: To determine whether obesity concurrent with sarcopenia (low muscle
      mass) or dynapenia (low muscle strength) is associated with increased falls risk
      in middle-aged and older adults. METHODS: 5-year prospective cohort study
      including 674 community-dwelling volunteers (mean +/- SD age 61.4 +/- 7.0 years;
      48% female). Sarcopenia and dynapenia were defined as lowest sex-specific
      tertiles for dual-energy X-ray (DXA)-assessed appendicular lean mass (adjusted
      for height and fat mass) or lower-limb strength, respectively. Obesity was
      defined as the highest tertiles of DXA-assessed total or trunk fat mass. Change
      in falls risk was calculated using the Physiological Profile Assessment (z
      scores: 0-1 = mild increased risk; 1-2 = moderate increased risk; >2 = marked
      increased risk). RESULTS: Multivariable linear regression analyses revealed mild
      but significantly increased falls risk scores for dynapenic obesity (change in
      mean z-score compared to non-dynapenic, non-obese group: 0.33, 95% CI 0.06-0.59
      [men] and 0.46, 95% CI 0.21-0.72 [women]) and dynapenia (0.25, 95% CI 0.05-0.46
      [women only]). CONCLUSIONS: Dynapenic obesity, but not sarcopenic obesity, is
      predictive of increased falls risk score in middle-aged and older adults. In
      clinical settings, muscle function assessments may be useful for predicting falls
      risk in obese patients.

PMID- 24585707
TI  - Feedforward and feedback connections and their relation to the cytox modules of
      V2 in Cebus monkeys.
AB  - To study the circuitry related to the ventral stream of visual information
      processing and its relation to the cytochrome oxidase (CytOx) modules in visual
      area V2, we injected anterograde and retrograde cholera toxin subunit B (CTb)
      tracer into nine sites in area V4 in five Cebus apella monkeys. The injection
      site locations ranged from 2 degrees  to 10 degrees  eccentricity in the lower
      visual field representation of V4. Alternate cortical sections, cut tangentially
      to the pial surface or in the coronal plane, were stained for CTb
      immunocytochemistry or for CytOx histochemistry or for Nissl. Our results
      indicate that the V4-projecting cells and terminal-like labeling were located in
      interstripes and thin CytOx-rich stripes and avoided the CytOx-rich thick stripes
      in V2. The feedforward projecting cell bodies in V2 were primarily located in the
      supragranular layers and sparsely located in the infragranular layers, whereas
      the feedback projections (i.e., the terminal-like labels) were located in the
      supra- and infragranular layers. V4 injections of CTb resulted in labeling of the
      thin stripes and interstripes of V2 and provided an efficient method of
      distinguishing the V2 modules that were related to the ventral stream from the
      CytOx-rich thick stripes, related to the dorsal stream. In V2, there was a
      significant heterogeneity in the distribution of projections: feedforward
      projections were located in CytOx-rich thin stripes and in the CytOx-poor
      interstripes, whereas the feedback projections were more abundant in the thin
      stripes than in the interstripes.

PMID- 24585710
TI  - Protein effects on surfactant adsorption suggest the dominant mode of surfactant
      mediated stabilization of protein.
AB  - Surfactants stabilize proteins through two major mechanisms: (1) their
      preferential location at nearby interfaces, in this way precluding protein
      adsorption; and/or (2) their association with protein into "complexes" that
      prevent proteins from interacting with surfaces as well as each other. However,
      selection of surfactants for protein stabilization currently is not typically
      made with benefit of any quantitative, predictive information to ensure that
      either mechanism will be enforced. We compared surface tension depression by
      poloxamer 188, polysorbate (PS) 80, and PS 20 in the presence and absence of
      lysozyme or a recombinant protein. The kinetic results were interpreted with
      reference to a mechanism for surfactant adsorption governed by the formation of a
      rate-limiting structural intermediate (i.e., an "activated complex") composed of
      surfactant and protein. The presence of protein was seen to increase the rate of
      surfactant adsorption in relation to surfactant acting alone for the PSs, with
      very little change in kinetics owing to protein in the case of poloxamer 188. A
      simple thermodynamic analysis indicated the presence of protein caused a
      reduction in DeltaG for the surfactant adsorption process, deriving entirely from
      a reduction in DeltaH. Thus, protein likely accelerates the adsorption of these
      surfactants by disrupting their self-associations, increasing the concentration
      of surfactant monomers near the interface.

PMID- 24585709
TI  - A review of rodent models of type 2 diabetic skeletal fragility.
AB  - Evidence indicating that adult type 2 diabetes (T2D) is associated with increased
      fracture risk continues to mount. Unlike osteoporosis, diabetic fractures are
      associated with obesity and normal to high bone mineral density, two factors that
      are typically associated with reduced fracture risk. Animal models will likely
      play a critical role in efforts to identify the underlying mechanisms of skeletal
      fragility in T2D and to develop preventative treatments. In this review we
      critically examine the ability of current rodent models of T2D to mimic the
      skeletal characteristics of human T2D. We report that although there are numerous
      rodent models of T2D, few have undergone thorough assessments of bone metabolism
      and strength. Further, we find that many of the available rodent models of T2D
      have limitations for studies of skeletal fragility in T2D because the onset of
      diabetes is often prior to skeletal maturation and bone mass is low, in contrast
      to what is seen in adult humans. There is an urgent need to characterize the
      skeletal phenotype of existing models of T2D, and to develop new models that more
      closely mimic the skeletal effects seen in adult-onset T2D in humans.

PMID- 24585711
TI  - Systems kinomics for characterizing host responses to high-consequence pathogens
      at the NIH/NIAID Integrated Research Facility-Frederick.
AB  - Currently, there is a paucity of information regarding the molecular pathogenesis
      for many high-consequence pathogens (HCPs) that pose threats to both national and
      international public health. In spite of this, investigations of the molecular
      pathogenesis for many HCPs have been limited to gross pathological changes in
      animal models or global analysis of gene expression. Further, questions remain
      regarding the ability of animal models of disease to recapitulate human molecular
      pathogenesis or act as predictors of therapeutic efficacy. Thus, it is likely
      that medical countermeasure development for HCPs will rely on identifying
      therapeutic targets that are uniquely modulated during HCP infection. It is also
      appreciated that many cellular processes can be regulated independently of
      changes in transcription or translation through phosphorylation events. Cellular
      kinases, individually or collectively (the kinome), play critical roles in
      regulating complex biology, underlie various malignancies, and represent high
      priority drug targets. The growing interest in kinases in both basic and
      translational research has driven efforts to develop technologies that enable
      characterization of phosphorylation-mediated signal transduction. To this end,
      enhanced technical capabilities at the IRF-Frederick provide the unique
      capability for characterizing host responses to HCP insult during the course of
      infection and identify novel targets for therapeutic intervention. 

PMID- 24585712
TI  - Natural reversal of left-right gut/gonad asymmetry in C. elegans males is
      independent of embryonic chirality.
AB  - Anatomical left-right (L/R) asymmetry in C. elegans is established in the four
      cell embryo as a result of anteroposterior skewing of transverse mitotic spindles
      with a defined handedness. This event creates a chiral embryo and ultimately an
      adult body plan with fixed L/R positioning of internal organs and components of
      the nervous system. While this "dextral" configuration is invariant in
      hermaphrodites, it can be reversed by physical manipulation of the early embryo
      or by mutations that interfere with mitotic spindle orientation, which leads to
      viable, mirror-reversed (sinistral) animals. During normal development of the C.
      elegans male, the gonad develops on the right of the midline, with the gut
      bilaterally apposed on the left. However, we found that in males of the
      laboratory N2 strain and Hawaiian ("Hw") wild isolate, the gut/gonad asymmetry is
      frequently reversed in a temperature-dependent manner, independent of normal
      embryonic chirality. We also observed sporadic errors in gonad migration
      occurring naturally during early larval stages of these and other wild strains;
      however, the incidence of such errors does not correlate with the frequency of
      L/R gut/gonad reversals in these strains. Analysis of N2/Hw hybrids and
      recombinant inbred advanced intercross lines (RIAILs) indicate that the L/R organ
      reversals are likely to result from recessively acting variations in multiple
      genes. Thus, unlike the highly reproducible L/R asymmetries of most structures in
      hermaphrodites, the L/R asymmetry of the male C. elegans body plan is less
      rigidly determined and subject to natural variation that is influenced by a
      multiplicity of genes.

PMID- 24585713
TI  - Proliferation, morphology, and pluripotency of mouse induced pluripotent stem
      cells in three different types of alginate beads for mass production.
AB  - Induced pluripotent stem cells (iPSCs) are expected to be an ideal cell source
      for biomedical applications, but such applications usually require a large number
      of cells. Suspension culture of iPSC aggregates can offer high cell yields but
      sometimes results in excess aggregation or cell death by shear stress. Hydrogel
      based microencapsulation can solve such problems observed in Suspension culture,
      but there is no systematic evaluation of the possible capsule formulations. In
      addition, their biological effects on entrapped cells are still poorly studied so
      far. We, therefore, immobilized mouse iPSCs in three different types of calcium
      alginate (Alg-Ca) hydrogel-based microcapsules; (i) Alg-Ca capsules without
      further treatment (Naked), (ii) Alg-Ca capsules with poly-l-lysine (PLL) coating
      (Coated), and (iii) Alg-PLL membrane capsules with liquid cores (Hollow). After
      10 days of culture within the medium containing serum and leukemia inhibitory
      factor, we obtained good cellular expansions (10-13-fold) in Coated and Hollow
      capsules that were similar to Suspension culture. However, 32 +/- 9% of cellular
      leakage and lower cell yield (about threefold) were observed in Naked capsules.
      This was not observed in Coated and Hollow capsules. In addition, immunostaining
      and quantitative RT-PCR showed that the formation of primitive endodermal layers
      was suppressed in Coated capsules contrary to all other formulations. This
      agenesis of primitive endoderm layers in Coated capsules is likely to be the main
      cause of the significantly better pluripotency maintenance in hydrogel-based
      encapsulation culture. These results are helpful in further optimizing hydrogel
      based iPSC culture, which can maintain better local cellular environments and be
      compatible with mass culture.

PMID- 24585714
TI  - The unique pharmacological characteristics of mifepristone (RU486): from
      terminating pregnancy to preventing cancer metastasis.
AB  - Mifepristone (RU486) is a born-for-woman molecule discovered three decades ago.
      Unlike those antihypertensive and antipsychotic pharmaceutical blockbusters, this
      abortifacient offers relatively low profit potential. Current understanding of
      mechanism of action of mifepristone and its on-going clinical trials are changing
      our views on the drug beyond its abortifacient scope. Here we briefly review its
      metabolism and pharmacokinetic properties including its unique enterohepatic
      circulation, its mechanisms of actions involving antiprogesterone and
      antiglucocorticoid, growth inhibition of various cancer cell lines, suppression
      of invasive and metastatic cancer potential, downregulation of Cdk2, Bcl-2, and
      NF-kappa B, interference of heterotypic cell adhesion to basement membrane, and
      cell migration. We comprehensively analyze recent results from preclinical and
      clinical studies using mifepristone as an anticancer drug for breast, meningioma,
      and gliomas tumors in the central nervous system, prostate cancer, ovarian and
      endometrial cancer, and gastric adenocarcinoma. Although mifepristone has more
      benefits for global public health than we originally thought, its effect as a
      postmetastatic chemotherapeutic agent is limited. Nonetheless, owing to its
      unique safe, metabolism and other pharmacological properties, metapristone (the
      primary metabolite of mifepristone) may have potential for cancer metastatic
      chemoprevention. 

PMID- 24585715
TI  - Pathogeneses of sudden cardiac death in national collegiate athletic association
      athletes.
AB  - BACKGROUND: The pathogenesis of sudden cardiac death in college athletes has not
      been defined by systematic case identification. METHODS AND RESULTS: A total of
      45 cases of sudden cardiac death were identified in National Collegiate Athletic
      Association (NCAA) athletes from 2004 to 2008 based on an internal reporting
      system and review of media reports. Autopsy reports were reviewed and adjudicated
      by a multidisciplinary panel. Cause of death could be reasonably determined in 36
      cases; 3 athletes had no autopsy, 5 autopsy reports could not be obtained, and 1
      autopsy had insufficient information to determine cause of death. The most common
      finding at death was a structurally normal heart or autopsy-negative sudden
      unexplained death (11, 31%), followed by coronary artery abnormalities (5, 14%),
      dilated cardiomyopathy (3, 8%), myocarditis related (3, 8%), aortic dissection
      (3, 8%), and idiopathic left ventricular hypertrophy/possible hypertrophic
      cardiomyopathy (HCM; 3, 8%). There was 1 case each (3%) of hypertrophic
      cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, long QT
      syndrome, commotio cordis, and Kawasaki disease. There was 1 case of death in a
      sickle cell positive athlete who also had left ventricular hypertrophy. The
      adjudicated diagnosis agreed with the official pathology report in only 59% of
      cases. CONCLUSIONS: Unexplained death with a structurally normal heart is the
      most common finding after suspected sudden cardiac death in NCAA athletes.
      Hypertrophic cardiomyopathy is infrequently seen, and conclusions in autopsy
      reports may not accurately reflect the pathological findings. Standardized
      protocols for cardiovascular autopsies in athletes are needed, including
      postmortem genetic testing, particularly in autopsy-negative cases.

PMID- 24585716
TI  - Mechanical alternans is associated with mortality in acute hospitalized heart
      failure: prospective mechanical alternans study (MAS).
AB  - BACKGROUND: Acute hospitalized heart failure (AHHF) is associated with 40% to 50%
      risk of death or rehospitalization within 6 months after discharge. Timely
      (before hospital discharge) risk stratification of patients with AHHF is crucial.
      We hypothesized that mechanical alternans (MA) and T-wave alternans (TWA) are
      associated with postdischarge outcomes in patients with AHHF. METHODS AND
      RESULTS: A prospective cohort study was conducted in the intensive cardiac care
      unit and enrolled 133 patients (59.6+/-15.7 years; 65% men) admitted with AHHF.
      Surface ECG and peripheral arterial blood pressure waveform via arterial line
      were recorded continuously during the intensive cardiac care unit stay. MA and
      TWA were measured by enhanced modified moving average method. All-cause death or
      heart transplant served as a combined primary end point. MA was observed in 28
      patients (25%), whereas TWA was detected in 33 patients (33%). If present, MA was
      tightly coupled with TWA. Mean TWA amplitude was larger in patients with both TWA
      and MA when compared with patients with lone TWA (median, 37 [interquartile
      range, 26-61] versus 22 [21-23] MUV; P=0.045). After a median of 10-month
      postdischarge, 42 (38%) patients died and 2 had heart transplants. MA was
      associated with the primary end point in univariable Cox model (hazard ratio,
      1.84; 95% confidence interval, 1.00-3.40; P=0.05) and after adjustment for left
      ventricular ejection fraction, New York Heart Association HF class, and implanted
      implantable cardioverter defibrillator/cardiac resynchronization therapy
      defibrillator (hazard ratio, 2.12 95% confidence interval, 1.13-3.98; P=0.020).
      TWA without consideration of simultaneous MA was not significantly associated
      with primary end point (hazard ratio, 1.42; 95% confidence interval, 0.77-2.64;
      P=0.260). CONCLUSIONS: MA is independently associated with outcomes in AHHF.
      CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique
      identifier: NCT01557465.

PMID- 24585717
TI  - Innate immunity is sufficient for the clearance of Chlamydia trachomatis from the
      female mouse genital tract.
AB  - Chlamydia muridarum and Chlamydia trachomatis, mouse and human strains,
      respectively, have been used to study immunity in a murine model of female
      genital tract infection. Despite evidence that unique genes of these otherwise
      genomically similar strains could play a role in innate immune evasion in their
      respective mouse and human hosts, there have been no animal model findings to
      directly support this conclusion. Here, we infected C57BL/6 and adaptive immune
      deficient Rag1(-/-) female mice with these strains and evaluated their ability to
      spontaneously resolve genital infection. Predictably, C57BL/6 mice spontaneously
      cleared infection caused by both chlamydial strains. In contrast, Rag1(-/-) mice
      which lack mature T and B cell immunity but maintain functional innate immune
      effectors were incapable of resolving C. muridarum infection but spontaneously
      cleared C. trachomatis infection. This distinct dichotomy in adaptive and innate
      immune-mediated clearance between mouse and human strains has important
      cautionary implications for the study of natural immunity and vaccine development
      in the mouse model.

PMID- 24585718
TI  - The myosin ID pathway and left-right asymmetry in Drosophila.
AB  - Drosophila is a classical model to study body patterning, however left-right
      (L/R) asymmetry had remained unexplored, until recently. The discovery of the
      conserved myosin ID gene as a major determinant of L/R asymmetry has revealed a
      novel L/R pathway involving the actin cytoskeleton and the adherens junction. In
      this process, the HOX gene Abdominal-B plays a major role through the control of
      myosin ID expression and therefore symmetry breaking. In this review, we present
      organs and markers showing L/R asymmetry in Drosophila and discuss our current
      understanding of the underlying molecular genetic mechanisms. Drosophila
      represents a valuable model system revealing novel strategies to establish L/R
      asymmetry in invertebrates and providing an evolutionary perspective to the
      problem of laterality in bilateria.

PMID- 24585719
TI  - Outcome and prognostic factors in patients with mantle-cell lymphoma relapsing
      after autologous stem-cell transplantation: a retrospective study of the European
      Group for Blood and Marrow Transplantation (EBMT).
AB  - BACKGROUND: Autologous stem-cell transplantation (autoSCT) is considered a
      standard treatment of non-frail patients with mantle cell lymphoma (MCL), but
      little is known about outcome of MCL patients relapsing after autoSCT. We
      therefore sought to analyse the outcome after autoSCT failure and the efficacy of
      a rescue stem-cell transplantation (SCT) in this setting. PATIENTS AND METHODS:
      Patients with MCL were eligible if they had relapsed after autoSCT performed
      between 2000 and 2009. A total of 1054 patients could be identified in the EBMT
      registry. By contacting the transplant centres, a full dataset could be retrieved
      for 360 patients. RESULTS: Median overall survival (OS) after relapse of the
      whole study group was 19 months. A long (>12 months) interval between autoSCT and
      relapse [P < 0.001, hazard ratio (HR) 0.62], primary refractory disease (P <
      0.02, HR 1.92), prior high-dose ARA-C treatment (P = 0.04, HR 1.43), and the year
      of relapse (P = 0.02, HR 0.92) significantly influenced OS from relapse in
      multivariate analysis. Eighty patients (22%) received a rescue allogeneic SCT
      (alloSCT). Relapse incidence, non-relapse mortality, and OS 2 years after alloSCT
      was 33% [confidence interval (95% CI 21% to 45%)], 30% (95% CI 19% to 42%), and
      46% (95% CI 33% to 59%), respectively. Remission duration after autoSCT was the
      only variable significantly affecting the outcome of salvage alloSCT. In
      contrast, rescue autoSCT was not associated with long-term disease control.
      However, individual patients survived long term even without salvage
      transplantation. CONCLUSIONS: MCL recurrence within 1 year after autoSCT has an
      extremely dismal outcome, while the prognosis of patients with longer remission
      durations after autoSCT is significantly better. AlloSCT may offer the
      possibility of durable survival when performed for patients with a remission
      duration of more than 12 months after first autoSCT, but the favourable effect of
      a salvage alloSCT in this setting needs further validation.

PMID- 24585720
TI  - Survival of patients with initially unresectable colorectal liver metastases
      treated with FOLFOX/cetuximab or FOLFIRI/cetuximab in a multidisciplinary concept
      (CELIM study).
AB  - BACKGROUND: Initially, unresectable colorectal liver metastases can be resected
      after response to chemotherapy. While cetuximab has been shown to increase
      response and resection rates, the survival outcome for this conversion strategy
      needs further evaluation. PATIENTS AND METHODS: Patients with technically
      unresectable and/or >=5 liver metastases were treated with FOLFOX/cetuximab (arm
      A) or FOLFIRI/cetuximab (arm B) and evaluated with regard to resectability every
      2 months. Tumour response and secondary resection data have been reported
      previously. A final analysis of overall survival (OS) and progression-free
      survival (PFS) was carried out in December 2012. RESULTS: Between December 2004
      and March 2008, 56 patients were randomised to arm A, 55 to arm B. The median OS
      was 35.7 [95% confidence interval (CI) 27.2-44.2] months [arm A: 35.8 (95% CI
      28.1-43.6), arm B: 29.0 (95% CI 16.0-41.9) months, HR 1.03 (95% CI 0.66-1.61), P
      = 0.9]. The median PFS was 10.8 (95% CI 9.3-12.2) months [arm A: 11.2 (95% CI 7.2
      15.3), arm B: 10.5 (95% CI 8.9-12.2) months, HR 1.18 (95% CI 0.79-1.74), P =
      0.4]. Patients who underwent R0 resection (n = 36) achieved a better median OS
      [53.9 (95% CI 35.9-71.9) months] than those who did not [21.9 (95% CI 17.1-26.7)
      months, P < 0.001]. The median disease-free survival for R0 resected patients was
      9.9 (95% CI 5.8-14.0) months, and the 5-year OS rate was 46.2% (95% CI 29.5% to
      62.9%). CONCLUSIONS: This study confirms a favourable long-term survival for
      patients with initially sub-optimal or unresectable colorectal liver metastases
      who respond to conversion therapy and undergo secondary resection. Both
      FOLFOX/FOLFIRI plus cetuximab, appear to be appropriate regimens for 'conversion'
      treatment in patients with K-RAS codon 12/13/61 wild-type tumours. Thus, liver
      surgery can be considered curative or alternatively as an additional 'line of
      therapy' in those patients who are not cured. CLINICAL TRIAL NUMBER: NCT00153998,
      www.clinicaltrials.gov.

PMID- 24585721
TI  - Addition of zoledronic acid to neoadjuvant chemotherapy does not enhance tumor
      response in patients with HER2-negative stage II/III breast cancer: the NEOZOTAC
      trial (BOOG 2010-01).
AB  - BACKGROUND: The role of zoledronic acid (ZA) when added to the neoadjuvant
      treatment of breast cancer (BC) in enhancing the clinical and pathological
      response of tumors is unclear. The effect of ZA on the antitumor effect of
      neoadjuvant chemotherapy has not prospectively been studied before. PATIENTS AND
      METHODS: NEOZOTAC is a national, multicenter, randomized study comparing the
      efficacy of TAC (docetaxel, adriamycin and cyclophosphamide i.v.) followed by
      granulocyte colony-stimulating factor on day 2 with or without ZA 4 mg i.v. q 3
      weeks inpatients withstage II/III, HER2-negative BC. We present data on the
      pathological complete response (pCR in breast and axilla), on clinical response
      using MRI, and toxicity. Post hoc subgroup analyses were undertaken to address
      the predictive value of menopausal status. RESULTS: Addition of ZA to
      chemotherapy did not improve pCR rates (13.2% for TAC+ZA versus 13.3% for TAC).
      Postmenopausal women (N = 96) had a numerical benefit from ZA treatment (pCR
      14.0% for TAC+ZA versus 8.7% for TAC, P = 0.42). Clinical objective response did
      not differ between treatment arms (72.9% versus 73.7%). There was no difference
      in grade III/IV toxicity between treatment arms. CONCLUSIONS: Addition of ZA to
      neoadjuvant chemotherapy did not improve pathological or clinical response to
      chemotherapy. Further investigations are warranted in postmenopausal women with
      BC, since this subgroup might benefit from ZA treatment.

PMID- 24585722
TI  - Maintenance bevacizumab-pemetrexed after first-line cisplatin-pemetrexed
      bevacizumab for advanced nonsquamous nonsmall-cell lung cancer: updated survival
      analysis of the AVAPERL (MO22089) randomized phase III trial.
AB  - BACKGROUND: The randomized, phase III AVAPERL trial evaluated the safety and
      efficacy of bevacizumab maintenance with or without pemetrexed in nonsquamous
      nonsmall-cell lung cancer (nsNSCLC). Progression-free survival (PFS) was
      significantly prolonged with bevacizumab-pemetrexed, but overall survival (OS)
      data were immature. In this article, we report an independent, updated analysis
      of survival outcomes in AVAPERL. PATIENTS AND METHODS: Patients with advanced
      nsNSCLC received first-line bevacizumab (7.5 mg/kg), cisplatin (75 mg/m(2)), and
      pemetrexed (500 mg/m(2)) every 3 weeks (q3w) for four cycles. Nonprogressing
      patients were randomized to maintenance bevacizumab (7.5 mg/kg) or bevacizumab
      pemetrexed (500 mg/m(2)) q3w until progression or consent withdrawal. The primary
      end point of the trial was PFS; in this independent OS analysis, participating
      study centers were contacted to collect survival data on patients still alive at
      the time of the first analysis. RESULTS: A total of 376 patients received
      induction treatment. Disease control was confirmed in 71.9% of patients; 253
      patients were randomized to maintenance treatment with bevacizumab (n = 125) or
      bevacizumab-pemetrexed (n = 128). At a median follow-up of 14.8 months, patients
      allocated to bevacizumab-pemetrexed had significantly improved PFS versus those
      on bevacizumab when measured from randomization [7.4 versus 3.7 months, hazard
      ratio (HR), 0.57, 95% confidence interval (CI) 0.44-0.75); P < 0.0001]. OS events
      occurred in 58% of all patients. OS was numerically longer with bevacizumab
      pemetrexed versus bevacizumab when measured from randomization [17.1 versus 13.2
      months, HR 0.87 (0.63-1.21); P = 0.29]. Second-line therapy was administered in
      77% and 70% of patients in the bevacizumab and bevacizumab-pemetrexed arms,
      respectively. No new adverse events were reported during this updated analysis.
      CONCLUSION: In an unselected population of nsNSCLC patients achieving disease
      control on platinum-based induction therapy, maintenance with bevacizumab
      pemetrexed was associated with a nonsignificant increase in OS over bevacizumab
      alone.

PMID- 24585723
TI  - Multicenter retrospective analysis of metastatic colorectal cancer (CRC) with
      high-level microsatellite instability (MSI-H).
AB  - BACKGROUND: The microsatellite instability-high (MSI-H) phenotype, present in 15%
      of early colorectal cancer (CRC), confers good prognosis. MSI-H metastatic CRC is
      rare and its impact on outcomes is unknown. We describe survival outcomes and the
      impact of chemotherapy, metastatectomy, and BRAF V600E mutation status in the
      largest reported cohort of MSI-H metastatic colorectal cancer (CRC). PATIENTS AND
      METHODS: A retrospective review of 55 MSI-H metastatic CRC patients from two
      institutions, Royal Melbourne Hospital (Australia) and The University of Texas MD
      Anderson Cancer Center (United States), was conducted. Statistical analyses
      utilized Kaplan-Meier method, Log-rank test, and Cox proportional hazards models.
      RESULTS: Median age was 67 years (20-90), 58% had poor differentiation, and 45%
      had stage IV disease at presentation. Median overall survival (OS) from
      metastatic disease was 15.4 months. Thirteen patients underwent R0/R1
      metastatectomies, with median OS from metastatectomy 33.8 months. Thirty-one
      patients received first-line systemic chemotherapy for metastatic disease with
      median OS from the start of chemotherapy 11.5 months. No statistically
      significant difference in progression-free survival or OS was seen between
      fluoropyrimidine, oxaliplatin, or irinotecan based chemotherapy. BRAF V600E
      mutation was present in 14 of 47 patients (30%). BRAF V600E patients demonstrated
      significantly worse median OS; 10.1 versus 17.3 months, P = 0.03. In multivariate
      analyses, BRAF V600E mutants had worse OS (HR 4.04; P = 0.005), while patients
      undergoing metastatectomy (HR 0.11; P = <0.001) and patients who initially
      presented as stage IV disease had improved OS (HR 0.27; P = 0.003). CONCLUSIONS:
      Patients with MSI-H metastatic CRC do not appear to have improved outcomes. BRAF
      V600E mutation is a poor prognostic factor in MSI-H metastatic CRC.

PMID- 24585724
TI  - The role of microemulsions in lipase-catalyzed hydrolysis reactions.
AB  - The kinetics of the p-nitrophenyl butyrate hydrolysis reaction, catalyzed by
      Candida rugosa lipase in the water-in-oil microemulsion cetyltrimethylammonium
      bromide/water/pentanol/hexane, was investigated. The results described in the
      present manuscript reveal two peculiar characteristics of the reaction: (i) the
      initial rate of hydrolysis is very fast and (ii) by decreasing the water content
      of the microemulsion, the reaction rate approaches the typical behavior of
      reactions performed in aqueous solution. In particular, for microemulsion systems
      with a high water content, the end points of the reactions are dictated by the
      shape stability of the microemulsion. For these systems, our methodological
      approach shows that the process follows a second-order kinetics equation,
      indicative of the dual role played by water, which is involved both as a
      component of the microemulsion, i.e., relevant for the microemulsion stability
      and as a reagent of the hydrolysis reaction. In contrast, for microemulsions
      containing a small amount of water, after the hydrolysis reaction the system
      seems to fall in the no existence range of the microemulsion. Accordingly, the
      kinetics results are more complex: in the initial stage, the reaction follows a
      zero-order kinetics equation, while for longer reaction times a first-order
      kinetics equation fits the experimental data, as would be expected for an
      enzymatic reaction in a homogeneous system.

PMID- 24585725
TI  - Peptide-based proteasome inhibitors in anticancer drug design.
AB  - The identification of the key role of the eukaryotic 26S proteasome in regulated
      intracellular proteolysis and its importance as a target in many pathological
      conditions wherein the proteasomal activity is defective (e.g., malignancies,
      autoimmune diseases, neurodegenerative diseases, etc.) prompted several research
      groups to the development of specific inhibitors of this multicatalytic complex
      with the aim of obtaining valid drug candidates. In regard to the anticancer
      therapy, the peptide boronate bortezomib (Velcade(r)) represents the first
      molecule approved by FDA for the treatment of multiple myeloma in 2003 and mantle
      cell lymphoma in 2006. Since then, a plethora of molecules targeting the
      proteasome have been identified as potential anticancer agents and a few of them
      reached clinical trials or are already in the market (i.e., carfilzomib;
      Kyprolis(r)). In most cases, the design of new proteasome inhibitors (PIs) takes
      into account a proven peptide or pseudopeptide motif as a base structure and
      places other chemical entities throughout the peptide skeleton in such a way to
      create an efficacious network of interactions within the catalytic sites. The
      purpose of this review is to provide an in-depth look at the current state of the
      research in the field of peptide-based PIs, specifically those ones that might
      find an application as anticancer agents. 

PMID- 24585726
TI  - Transposable elements and psychiatric disorders.
AB  - Transposable Elements (TEs) or transposons are low-complexity elements (e.g.,
      LINEs, SINEs, SVAs, and HERVs) that make up to two-thirds of the human genome.
      There is mounting evidence that TEs play an essential role in genomic
      architecture and regulation related to both normal function and disease states.
      Recently, the identification of active TEs in several different human brain
      regions suggests that TEs play a role in normal brain development and adult
      physiology and quite possibly in psychiatric disorders. TEs have been implicated
      in hemophilia, neurofibromatosis, and cancer. With the advent of next-generation
      whole-genome sequencing approaches, our understanding of the relationship between
      TEs and psychiatric disorders will greatly improve. We will review the biology of
      TEs and early evidence for TE involvement in psychiatric disorders.

PMID- 24585727
TI  - Arrhythmogenic right ventricular dysplasia/cardiomyopathy and cardiac
      sarcoidosis: distinguishing features when the diagnosis is unclear.
AB  - BACKGROUND: Cardiac sarcoidosis (CS) may show overlap in the clinical
      presentation with arrhythmogenic right ventricular dysplasia/cardiomyopathy
      (ARVD/C). We sought to investigate patients with CS who were misdiagnosed with
      ARVD/C and identify clinical features to distinguish these 2 groups. METHODS AND
      RESULTS: Among patients enrolled in the Johns Hopkins ARVD/C registry, 15
      patients with definite 2010 diagnostic criteria for ARVD/C were subsequently
      diagnosed with CS. Forty-two pathogenic desmosomal mutation carriers with
      definite ARVD/C based on the 2010 diagnostic criteria served as a control group.
      Patients with CS were older at the age of symptom onset, more likely to have
      comorbidities, and develop heart failure symptoms over time (P<0.05).
      Electrocardiographically, PR interval prolongation and high-grade
      atrioventricular block were exclusively associated with CS (P<0.05). HV interval
      prolongation and increased number of ventricular tachycardias induced were also
      associated with CS (P<0.05). Radiographically, significant left ventricular
      dysfunction, myocardial delayed enhancement of the septum, and mediastinal
      lymphadenopathy were more often see in those with CS (P<0.05). CONCLUSIONS: The
      2010 diagnostic criteria for ARVD/C have limited discrimination in distinguishing
      between ARVD/C and CS. Despite the overlay in clinical presentation, older age of
      symptom onset, presence of cardiovascular comorbidities, nonfamilial pattern of
      disease, PR interval prolongation, high-grade atrioventricular block, significant
      left ventricular dysfunction, myocardial delayed enhancement of the septum, and
      mediastinal lymphadenopathy should raise the suspicion for CS.

PMID- 24585728
TI  - A personal history of research on microbial biofilms and biofilm infections.
AB  - The observation of aggregated microorganisms surrounded by a self-produced matrix
      adhering to surfaces or located in tissues or secretions is as old as
      microbiology, with both Leeuwenhoek and Pasteur describing the phenomenon. In
      environmental and technical microbiology, biofilms were already shown 80-90 years
      ago to be important for biofouling on submerged surfaces, e.g. ships. The concept
      of biofilm infections and their importance in medicine is, however, < 40 years
      old and was started by Jendresen's observations of acquired dental pellicles and
      my own observations of heaps of Pseudomonas aeruginosa cells in sputum and lung
      tissue from chronically infected cystic fibrosis patients. The term biofilm was
      introduced into medicine in 1985 by Costerton. In the following decades, it
      became obvious that biofilm infections are widespread in medicine, and their
      importance is now generally accepted.

PMID- 24585729
TI  - Comment on Tu et al. 2013. A critical evaluation of statistical approaches to
      examining the role of growth trajectories in the developmental origins of health
      and disease.

PMID- 24585730
TI  - Cohort Profile: Longitudinal Study of Adult Health (ELSA-Brasil).
AB  - Chronic diseases are a global problem, yet information on their determinants is
      generally scant in low- and middle-income countries. The Brazilian Longitudinal
      Study of Adult Health (ELSA-Brasil) aims to contribute relevant information
      regarding the development and progression of clinical and subclinical chronic
      diseases, particularly cardiovascular diseases and diabetes, in one such setting.
      At Visit 1, we enrolled 15 105 civil servants from predefined universities or
      research institutes. Baseline assessment (2008-10) included detailed interviews
      and measurements to assess social and biological determinants of health, as well
      as various clinical and subclinical conditions related to diabetes,
      cardiovascular diseases and mental health. A second visit of interviews and
      examinations is under way (2012-14) to enrich the assessment of cohort exposures
      and to detect initial incident events. Annual surveillance has been conducted
      since 2009 for the ascertainment of incident events. Biological samples (sera,
      plasma, urine and DNA) obtained at both visits have been placed in long-term
      storage. Baseline data are available for analyses, and collaboration via specific
      research proposals directed to study investigators is welcome. 

PMID- 24585731
TI  - Authors' reply to the letter to the editor by Wills et al.

PMID- 24585732
TI  - Commentary: Three worlds collide: Berkson's bias, selection bias and collider
      bias.

PMID- 24585733
TI  - Commentary: Berkson's fallacy and missing data.

PMID- 24585734
TI  - Limitations of the application of fourfold table analysis to hospital data.

PMID- 24585735
TI  - Commentary: A structural approach to Berkson's fallacy and a guide to a history
      of opinions about it.

PMID- 24585736
TI  - Cross-national and historical differences in subjective well-being.
AB  - BACKGROUND: There is a growing body of population survey data on national
      subjective well-being which allows comparisons across countries and across
      periods. Key issues in this work are as follows. Can response to questions on
      well-being be meaningfully compared across countries and periods? What social
      conditions are associated with greater well-being both between countries and
      across periods? Are there lessons for how global well-being might be improved?
      This review aims to give an overview of this area and its relevance to
      psychiatric epidemiology. METHODS: Systematic searches of the literature were
      carried out using eight academic databases between August 2012 and January 2013.
      RESULTS: Subjective well-being involves multiple components, including cognitive
      evaluation of satisfaction with life and emotional state, and these are separable
      from mental ill health. Although there are difficulties in measuring subjective
      well-being in comparable ways cross-culturally, there is sufficient evidence of
      validity to make comparisons meaningful. The subjective well-being of nations
      increases with income per capita, but gains are smaller in higher-income
      countries. Other national factors that affect well-being include income
      inequality, social welfare, individualism, democracy and freedom, social capital
      and physical health. CONCLUSIONS: Economic growth of lower-income nations will
      improve global subjective well-being. However, this needs to be sustainable or it
      will reduce the well-being of future generations. Higher-income nations need to
      focus on other determinants of well-being. Research on cross-national well-being
      suggests a number of directions that may be profitably pursued in psychiatric
      epidemiology.

PMID- 24585738
TI  - "High Content Imaging for the Morphometric Diagnosis and Immunophenotypic
      Prognosis of Canine Lymphomas"
AB  - Background: The common, symptomatic form of canine lymphoma (multicentric, medium
      to-large cell, advanced) is consistently diagnosed manually and qualitatively by
      veterinary cytologists based on increased lymphocyte size. The most effective
      prognostic feature is immunophenotype based on dual-antibody labeling for T
      versus B cells. High Content Imaging (HCI) is a novel, semi-automated,
      fluorescence microscopy and image-analysis technology used in research and
      predictive toxicology. Objective: We tested the hypothesis that HCI could semi
      automatise the quantitative diagnosis of canine lymphoma and simultaneously
      determine immunophenotypic prognosis. Methods: Lymphocytes were obtained from
      lymph nodes of 6 lymphoma-free and 5 lymphomatous dogs, stained with antibodies
      against CD21 and CD3 (B- vs. T- cells), Hoechst-33342 and seeded into 96-well
      plates. Morphological parameters were examined: a) cell area, b) nuclear area, c)
      nuclear displacement, d) cytoplasmic area, e) nucleus to cell area ratio
      (N/Cell), f) nucleus to cytoplasm ratio (N/Cyt), g) cell roundness. Results: HCI
      unequivocally discriminated malignant from benign lymphocytes, and provided
      immunophenotype. Cell and cytoplasmic area, nuclear displacement and roundness
      showed biggest differences without value overlap between groups. Mean/ median/SD
      for control versus lymphoma samples were: a) cell area (um2 ): 55.5/53.6/7.5
      versus 80.3/75.5/8.7, b) nuclear area (um2 ): 33.4/34.8/3.5 versus 40.2/38.5/5,
      c) cytoplasm area (um2 ): 22.1/216.2 versus 40/38.4/4.9, d) N/Cell:
      0.62/0.62/0.06 versus 0.52/0.52/0.03, e) nuclear displacement (arbitrary units):
      0.139/0.149/0.055 versus 0.33/0.30//0.056, f) N/Cyt: 1.84/1.76/0.44 versus
      1.19/1.24/0.17, g) roundness index: 1.22/1.21/0.03 versus 1.42/ 1.42/0.11
      (p<0.05). Conclusion: HCI identified several, novel, morphometric parameters that
      effectively diagnose the common, symptomatic form of canine lymphoma, and also
      simultaneously determine prognostic immunophenotype. (c) 2014 Clinical Cytometry
      Society.

PMID- 24585740
TI  - Retraction.

PMID- 24585737
TI  - The emergence of the Middle East respiratory syndrome coronavirus.
AB  - On September 20, 2012, a Saudi Arabian physician reported the isolation of a
      novel coronavirus from a patient with pneumonia on ProMED-mail. Within a few
      days, the same virus was detected in a Qatari patient receiving intensive care in
      a London hospital, a situation reminiscent of the role air travel played in the
      spread of severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002. SARS
      CoV originated in China's Guangdong Province and affected more than 8000 patients
      in 26 countries before it was contained 6 months later. Over a year after the
      emergence of this novel coronavirus--Middle East respiratory syndrome coronavirus
      (MERS-CoV)--it has caused 178 laboratory-confirmed cases and 76 deaths. The
      emergence of a second highly pathogenic coronavirus within a decade highlights
      the importance of a coordinated global response incorporating reservoir
      surveillance, high-containment capacity with fundamental and applied research
      programs, and dependable communication pathways to ensure outbreak containment.
      Here, we review the current state of knowledge on the epidemiology, ecology,
      molecular biology, clinical features, and intervention strategies of the novel
      coronavirus, MERS-CoV.

PMID- 24585739
TI  - Developmental changes in brain activation involved in the production of novel
      speech sounds in children.
AB  - Older children are more successful at producing unfamiliar, non-native speech
      sounds than younger children during the initial stages of learning. To reveal the
      neuronal underpinning of the age-related increase in the accuracy of non-native
      speech production, we examined the developmental changes in activation involved
      in the production of novel speech sounds using functional magnetic resonance
      imaging. Healthy right-handed children (aged 6-18 years) were scanned while
      performing an overt repetition task and a perceptual task involving aurally
      presented non-native and native syllables. Productions of non-native speech
      sounds were recorded and evaluated by native speakers. The mouth regions in the
      bilateral primary sensorimotor areas were activated more significantly during the
      repetition task relative to the perceptual task. The hemodynamic response in the
      left inferior frontal gyrus pars opercularis (IFG pOp) specific to non-native
      speech sound production (defined by prior hypothesis) increased with age.
      Additionally, the accuracy of non-native speech sound production increased with
      age. These results provide the first evidence of developmental changes in the
      neural processes underlying the production of novel speech sounds. Our data
      further suggest that the recruitment of the left IFG pOp during the production of
      novel speech sounds was possibly enhanced due to the maturation of the neuronal
      circuits needed for speech motor planning. This, in turn, would lead to
      improvement in the ability to immediately imitate non-native speech.

PMID- 24585741
TI  - Impact of rheumatoid arthritis on receiving a diagnosis of hypertension among
      patients with regular primary care.
AB  - OBJECTIVE: Despite numerous studies reporting increased cardiovascular disease
      (CVD) in patients with rheumatoid arthritis (RA), the impact of RA on managing
      modifiable CVD risk factors remains understudied. We tested the hypothesis that
      RA is a risk factor for not receiving a hypertension diagnosis. METHODS: Using a
      cohort design, we studied adult patients with and without RA/inflammatory
      arthritis from a large academic multispecialty practice. All were seen regularly
      in primary care and met clinical guideline hypertension criteria, but lacked
      prior hypertension diagnosis/treatment. The primary outcome was time to
      International Classification of Diseases, Ninth Revision code for hypertension or
      elevated blood pressure, or antihypertensive medication prescription. Kaplan
      Meier survival curve analysis and Cox proportional hazards modeling were used to
      examine the impact of RA on diagnosis of hypertension. RESULTS: Among 14,974
      patients with undiagnosed hypertension, 201 patients had RA codes. RA patients
      had equivalent primary care visits and more total visits compared to patients
      without RA. At the end of the study, the likelihood of hypertension diagnosis was
      36% in RA patients compared to 51% in patients without RA. In adjusted Cox
      models, RA patients had a 29% lower hypertension diagnosis hazard (hazard ratio
      0.71, 95% confidence interval 0.55-0.93), reflecting more undiagnosed
      hypertension than with other comorbidities. CONCLUSION: Among patients meeting
      guideline-based hypertension criteria, RA patients were less likely to be
      diagnosed despite more visits than those without RA. Given heightened CVD risks
      in RA and the importance of hypertension diagnosis as a first step toward
      controlling risk, rheumatologists should collaborate to improve rates of
      diagnosis for this modifiable CVD risk factor.

PMID- 24585743
TI  - Innovators.

PMID- 24585744
TI  - Norman Barrett (1903-79): unorthodox pioneer of thoracic and oesophageal surgery.
AB  - It is an interesting quirk of medical history that the legacy of Norman Barrett
      most ostensibly lies in the name of a disease the he was quite emphatically wrong
      about, at least when he first described it. Indeed, there are those who argue to
      remove the eponym in favour of the title 'Columnar Lined Epithelium', in part
      because of what little Barrett actually had to do with the correct initial
      characterization of this disease. Yet the sum of Norman Barrett's contributions
      to modern medicine is much more than a mistaken characterization of a
      pathological process. Barrett was truly a pioneer of chest surgery in the UK - a
      specialty in its embryonic stages when he first qualified. He was also renowned
      as a teacher and academic of the highest calibre. In tracing the story of his
      life we can see how his natural attributes, life experiences and keen
      appreciation of the arts (especially history) facilitated personal success and
      such sharp insight into the vagaries of modern academic medicine. 

PMID- 24585742
TI  - Desensitization of myofilaments to Ca2+ as a therapeutic target for hypertrophic
      cardiomyopathy with mutations in thin filament proteins.
AB  - BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a common genetic disorder caused
      mainly by mutations in sarcomeric proteins and is characterized by maladaptive
      myocardial hypertrophy, diastolic heart failure, increased myofilament Ca(2+)
      sensitivity, and high susceptibility to sudden death. We tested the following
      hypothesis: correction of the increased myofilament sensitivity can delay or
      prevent the development of the HCM phenotype. METHODS AND RESULTS: We used an HCM
      mouse model with an E180G mutation in alpha-tropomyosin (Tm180) that demonstrates
      increased myofilament Ca(2+) sensitivity, severe hypertrophy, and diastolic
      dysfunction. To test our hypothesis, we reduced myofilament Ca(2+) sensitivity in
      Tm180 mice by generating a double transgenic mouse line. We crossed Tm180 mice
      with mice expressing a pseudophosphorylated cardiac troponin I (S23D and S24D;
      TnI-PP). TnI-PP mice demonstrated a reduced myofilament Ca(2+) sensitivity
      compared with wild-type mice. The development of pathological hypertrophy did not
      occur in mice expressing both Tm180 and TnI-PP. Left ventricle performance was
      improved in double transgenic compared with their Tm180 littermates, which
      express wild-type cardiac troponin I. Hearts of double transgenic mice
      demonstrated no changes in expression of phospholamban and sarcoplasmic reticulum
      Ca(2+) ATPase, increased levels of phospholamban and troponin T phosphorylation,
      and reduced phosphorylation of TnI compared with Tm180 mice. Moreover, expression
      of TnI-PP in Tm180 hearts inhibited modifications in the activity of
      extracellular signal-regulated kinase and zinc finger-containing transcription
      factor GATA in Tm180 hearts. CONCLUSIONS: Our data strongly indicate that
      reduction of myofilament sensitivity to Ca(2+) and associated correction of
      abnormal relaxation can delay or prevent development of HCM and should be
      considered as a therapeutic target for HCM.

PMID- 24585745
TI  - Dr Thomas Aitchison Latta (c1796-1833): pioneer of intravenous fluid replacement
      in the treatment of cholera.
AB  - In 1832 pandemic cholera travelled across Europe with devastating mortality.
      Before this, doctors had speculated on the benefits of intravenous therapy but
      none had tried. Only in 1832 did Thomas Latta perform intravenous infusions. This
      treatment disappeared after Latta's death. This was mainly due to general medical
      scepticism, lack of biochemical and physiological knowledge and poor patient
      selection. Finally, there were no further pandemics comparable with that of 1832
      to provide the catalyst to accelerate medical development in this field. 

PMID- 24585746
TI  - Electrical treatment of spinal cord injuries in the 18th and 19th centuries.
AB  - Two centuries ago, electricity was being used for the treatment of paraplegia and
      trials were taking place in France. This study aims to identify cases of
      traumatic paraplegia treated with electricity in the 19th century in order to
      assess the therapeutic benefit. Only four such cases were identified, none with a
      complete transection of the spinal cord since these patients would have died from
      pressure sores and urinary tract infections. The personalities involved, William
      Gull, William Erb, Guillaume Duchenne and Cyril Henry Golding Bird are portrayed
      and contemporaneous views on electrotherapy analysed. While the four patients
      apparently benefited from the treatment, the lack of follow-up and the incomplete
      data prevented a definitive conclusion on the therapeutic value of electrical
      treatment in traumatic paraplegia. 

PMID- 24585747
TI  - Medicus Petrus Hispanus (c1205-77 Peter of Spain): a XIII century Pope and Author
      of a Medieval Sex Guide.
AB  - Petrus Hispanus was the only practicing physician ever to become Pope (1276-77).
      By all accounts he was an interim choice when rival French and Italian Cardinals
      could not elect one of their own nationality. Although not clearly responsible
      for any major political actions by the Church, Petrus was famous for several
      centuries after his death because of his secular writings - a text on logic
      (Summulae logicales) and a handbook on medicine (Thesaurus pauperum). The latter
      is noteworthy because it contains two sections on coitus - how to enhance the
      sexual act and how to subdue sexual urges. Promoting coitus seems an odd topic
      for a medieval Catholic cleric-writer and raises the question as to whether the
      first section may have been added by a later copyist or editor, but an
      examination of a very early manuscript of the Thesaurus gives assurance that the
      two sexual sections were written by Petrus, probably around 1270. 

PMID- 24585748
TI  - To what extent did the 1858 Medical Act bring unity to the British medical
      profession?
AB  - The Medical Act of 1858 was the culmination of medical, political and social
      wrangling for several decades before its passage. This essay looks to place the
      Act in its correct historical context and will specifically consider whether it
      brought about unity to what was a disparate and factional profession. That it was
      an important piece of legislation in the history of British healthcare is
      unquestioned, but the extent to which it directly brought about change is more
      uncertain. In order to understand the background, content and repercussions of
      the Act, one must recognize the structure of the medical system at that time. One
      reason for doing this, as argued by some, is that the Medical Act, like the
      Apothecaries Act of 1815, was the result of changes to the profession and not the
      cause of them. Reformists hoped that the Medical Act would unify the profession,
      yet significant historical, hierarchical and political barriers stood in the way
      of reform. 

PMID- 24585749
TI  - Edith (1869-1938) and Florence (1870-1932) Stoney, two Irish sisters and their
      contribution to radiology during the World War I.
AB  - Edith and Florence Stoney, two sisters born in Dublin and working in London,
      responded to the summons of suffragists and offered themselves for medical
      service in World War I. Each had a strong scientific background and experience
      that they were able to use in setting up and running radiological services in
      Belgium, France, Serbia and Macedonia. The British War Office was reluctant to
      employ women doctors but the work Florence and her colleagues achieved persuaded
      Sir Alfred Keogh that Florence should be the first woman doctor to be employed in
      a military hospital in England. 

PMID- 24585750
TI  - William Sampson Handley (1872-1962): champion of the permeation theory of
      dissemination of breast cancer.
AB  - The Halsted radical mastectomy that prevailed in the first half of the 20th
      century derived its scientific basis from the 'lymphatic permeation theory' of
      William Sampson Handley, an Honorary Senior Consulting Surgeon and former Vice
      President of the Royal College of Surgeons. Through his pioneering work in the
      cancer research laboratories at the Middlesex Hospital in London, Handley
      propounded the theory of centrifugal lymphatic permeation as the leading
      mechanism for the spread of cancer. This work won him worldwide renown and
      celebrated recognition in 1911 from the Royal College of Surgeons of England for
      the best work in the pathology and therapeutics in cancer. During his active life
      he was one of the great names and influences in the world of surgery. He held
      many roles at the Royal College of Surgeons and was involved with the
      international surgical fraternity. His philosophy of the uniqueness of the
      individual and his kind and courteous disposition won him praise from juniors,
      colleagues and patients alike. Although much of his work was rejected later, much
      still remains noteworthy in the history of surgery and cancer research. 

PMID- 24585751
TI  - The Protestant medical missions to China: the introduction of Western medicine
      with vaccination.
AB  - Modern medicine in China began with the arrival of Anglo-American Protestant
      missionaries in the early 19th century. Conditions were vastly different from the
      times of the Jesuits in Peking during the 17th and 18th centuries, when the
      priests enjoyed the endorsement of the Court and high officials. Faced with
      hostile and xenophobic officialdom and populace, surgeons of the British East
      India Company in collaboration with missionaries took the initiative. In 1805 Dr
      Alexander Pearson (1780-1874) introduced smallpox vaccination in Macao and
      Canton. Reverend Dr Robert Morrison (1782-1834) of the London Missionary Society
      with another East India Company Surgeon, Dr John Livingstone (1829) opened a
      dispensary for the poor in Macao in 1820. These pioneers paved the way for later
      Anglo-American medical missionaries who revolutionized medical practice in China.

PMID- 24585752
TI  - The protestant medical missions to China: Dr Thomas Richardson Colledge (1796
      1879) and the founding of the Macao Ophthalmic Hospital.
AB  - A surgeon of the British East India Company, Dr Thomas Richardson Colledge,
      founded the Macao Ophthalmic Hospital in 1827. This was not only the first
      Western hospital ever opened in China for the purpose of bringing modern medicine
      to the Chinese but also the precursor of similar efforts of later medical
      missions in China. The gratifying results of this institute proved that employing
      Western medicine was an effective way to introduce Christianity to China and to
      open her door to the outside world. Though not a missionary himself, Colledge is
      rightfully regarded as the originator of medical missionaries to China. 

PMID- 24585753
TI  - Pathology in four epochs: Max Borst (1869-1946), Chairman of Pathology at Munich
      University from 1910-46.
AB  - Max Borst was the pre-eminent tumour pathologist among Rudolf Virchow's (1821
      1902) heirs. In his magnum opus of 1902 Borst established the first complete
      system of tumours based upon histogenetic and biological criteria. Borst was the
      Chairman of Pathology at Munich University from 1910-46, over a unique period in
      German history. In the 1930s he was the leading figure in German cancer research.
      Borst was no Nazi but neither did he join the Resistance. He came to an
      arrangement with the National Socialist regime, living with it in a relationship
      of mutual utilitarianism. He never belonged to a political party and he
      cultivated an image of an apolitical professor except for his engagement against
      the Raterepublik (Bavarian Soviet Republic) in 1918/19. During World War I, Borst
      was the first German pathologist to establish systematic 'war pathology' and he
      served in the Army again in World War II as a septuagenarian. Art played an
      important part in his life. As a gifted musician he performed publicly and he
      published songs. Borst was an Idealist and Neo-Vitalist who always felt more
      obliged to authenticity and truthfulness than to truth. He died in a car crash in
      the Bavarian uplands in October 1946. 

PMID- 24585754
TI  - New insights into the pathogenesis and management of lupus in children.
AB  - Systemic lupus erythematosus (SLE) is the archetypal systemic autoimmune disease,
      characterised by inflammation causing a wide spectrum of major clinical
      manifestations that may affect any organ. Childhood-onset SLE (cSLE) is more
      severe with greater damage and drug burden than adult-onset SLE. Understanding
      the pathogenesis of cSLE is a key step in directing medical management. The
      dysregulated immune system, that in health is usually vital in protecting the
      body from infection, contributes significantly to the disease process. Improved
      knowledge of disease mechanism will help to identify potential targets for novel
      agents and the identification of new biomarkers of disease activity. This review
      will present current knowledge of the innate and adaptive immune responses in
      cSLE and the optimal patient management that aims to control the disease. Innate
      immune dysregulation includes the overexpression of interferon-alpha, dendritic
      cell activation, neutrophil extracellular traps and phagocyte abnormalities. The
      classical adaptive immune system is over activated in lupus with excessive
      autoantibody production due to abnormalities in B and T cell regulation. Novel
      biologic medications are being developed to specifically target these areas with
      the ultimate aim of improving the long-term outlook and quality of life for
      children living with Lupus. 

PMID- 24585755
TI  - Pandemic A/H1N1 2009 influenza vaccination, preceding infections and clinical
      findings in UK children with Guillain-Barre syndrome.
AB  - OBJECTIVE: To record clinical findings in all new cases of Guillain-Barre
      syndrome (GBS) or Fisher syndrome (FS) in UK children in the 2 years following
      September 2009 and determine the proportion temporally associated with recent
      infections, pandemic H1N1 (2009) strain influenza vaccination or seasonal
      influenza vaccination. DESIGN: A prospective UK-wide epidemiological study using
      the British Paediatric Surveillance Unit system. PATIENTS: Children aged 16 years
      or less meeting the Brighton Collaboration criteria for GBS or FS. RESULTS: 112
      children with GBS (66 boys and 46 girls) and 3 boys with FS were identified in 2
      years. All but one recovered sufficiently to go home. The annual UK incidence
      rate of GBS in patients less than 15 years old was 0.45/100 000, similar to other
      countries. There was evidence of infection in the 3 months preceding onset in
      92/112 GBS and 3/3 FS cases. Of those living in England, 7 cases received
      pandemic A/H1N1 2009 influenza vaccination before GBS symptom onset (3/7 were
      within 6 months including 1 within 3 months); 2 children received 2010/2011
      seasonal influenza vaccination within 6 months of GBS onset. The numbers
      vaccinated were not significantly greater than expected by chance. CONCLUSIONS:
      The outcome for childhood GBS and FS after 6 months was better than reported in
      adults. Most UK GBS and FS cases had infections in the preceding 3 months. When
      considering the children living in England, there was no significantly increased
      risk of GBS after pandemic A/H1N1 2009 influenza vaccination or 2010/2011
      seasonal influenza vaccination.

PMID- 24585757
TI  - Lost in transition: discrepancies in how physicians perceive the actionability of
      the results of tests pending at discharge.

PMID- 24585758
TI  - Prediction of fetal hemoglobin in sickle cell anemia using an ensemble of genetic
      risk prediction models.
AB  - BACKGROUND: Fetal hemoglobin (HbF) is the major modifier of the clinical course
      of sickle cell anemia. Its levels are highly heritable, and its interpersonal
      variability is modulated in part by 3 quantitative trait loci that affect HbF
      gene expression. Genome-wide association studies have identified single
      nucleotide polymorphisms (SNPs) in these quantitative trait loci that are highly
      associated with HbF but explain only 10% to 12% of the variance of HbF. Combining
      SNPs into a genetic risk score can help to explain a larger amount of the
      variability of HbF level, but the challenge of this approach is to select the
      optimal number of SNPs to be included in the genetic risk score. METHODS AND
      RESULTS: We developed a collection of 14 models with genetic risk score composed
      of different numbers of SNPs and used the ensemble of these models to predict HbF
      in patients with sickle cell anemia. The models were trained in 841 patients with
      sickle cell anemia and were tested in 3 independent cohorts. The ensemble of 14
      models explained 23.4% of the variability in HbF in the discovery cohort, whereas
      the correlation between predicted and observed HbF in the 3 independent cohorts
      ranged between 0.28 and 0.44. The models included SNPs in BCL11A, the HBS1L-MYB
      intergenic region, and the site of the HBB gene cluster, quantitative trait loci
      previously associated with HbF. CONCLUSIONS: An ensemble of 14 genetic risk
      models can predict HbF levels with accuracy between 0.28 and 0.44, and the
      approach may also prove useful in other applications.

PMID- 24585761
TI  - What do we know about the medical biography of Kemal Ataturk (1881-1938)? A
      summary of the state of knowledge and outlook on relevant issues for further
      research.
AB  - Mustafa Kemal Ataturk, the founder and first President of the Turkish republic,
      is the subject of many more or less 'heroic' biographies and few critical ones.
      His anamnesis, however, is only available in fragments. Many books omit details
      of Ataturk's health and life, for example his bloodline, his illness and
      eventually his death, his funeral prayer and ceremony and his burial. His liver
      problem, diagnosed as cirrhosis and said to be the cause of his death, is well
      described but his general health and other sicknesses are scarcely recorded. This
      paper provides an overview of his anamnesis as far as it is known, the literature
      describing it and the level of knowledge generally published, and it also
      indicates where original research in the archives is needed to complete the
      picture. 

PMID- 24585759
TI  - Protein kinase A-phosphorylated KV1 channels in PSD95 signaling complex
      contribute to the resting membrane potential and diameter of cerebral arteries.
AB  - RATIONALE: Postsynaptic density-95 (PSD95) is a scaffolding protein that
      associates with voltage-gated, Shaker-type K(+) (KV1) channels and promotes the
      expression of KV1 channels in vascular smooth muscle cells of the cerebral
      (cVSMCs) circulation. However, the physiological role of PSD95 in mediating
      molecular signaling in cVSMCs is unknown. OBJECTIVE: We explored whether a
      specific interaction between PSD95 and KV1 channels enables protein kinase A
      phosphorylation of KV1 channels in cVSMCs to promote vasodilation. METHODS AND
      RESULTS: Rat cerebral arteries were used for analyses. A membrane-permeable
      peptide (KV1-C peptide) corresponding to the postsynaptic density-95, discs
      large, zonula occludens-1 binding motif in the C terminus of KV1.2alpha was
      designed as a dominant-negative peptide to disrupt the association of KV1
      channels with PSD95. Application of KV1-C peptide to cannulated, pressurized
      cerebral arteries rapidly induced vasoconstriction and depolarized cVSMCs. These
      events corresponded to reduced coimmunoprecipitation of the PSD95 and KV1
      proteins without altering surface expression. Middle cerebral arterioles imaged
      in situ through cranial window also constricted rapidly in response to local
      application of KV1-C peptide. Patch-clamp recordings confirmed that KV1-C peptide
      attenuates KV1 channel blocker (5-(4-phenylalkoxypsoralen))-sensitive current in
      cVSMCs. Western blots using a phospho-protein kinase A substrate antibody
      revealed that cerebral arteries exposed to KV1-C peptide showed markedly less
      phosphorylation of KV1.2alpha subunits. Finally, phosphatase inhibitors blunted
      both KV1-C peptide-mediated and protein kinase A inhibitor peptide-mediated
      vasoconstriction. CONCLUSIONS: These findings provide initial evidence that
      protein kinase A phosphorylation of KV1 channels is enabled by a dynamic
      association with PSD95 in cerebral arteries and suggest that a disruption of such
      association may compromise cerebral vasodilation and blood flow.

PMID- 24585762
TI  - The other Founding Physicks: the lives and times of the physician signers of the
      Articles of Confederation and Perpetual Union.
AB  - The Articles of Confederation and Perpetual Union was the interim constitution of
      the United States of America between 1777 and 1789. The name the United States of
      America is encountered here for the first time. Three physicians were among the
      48 signers - Josiah Bartlett, Samuel Holten and Nathaniel Scudder. All three men
      started out studying and practising medicine but their lives took very different
      turns as the new nation emerged. 

PMID- 24585763
TI  - The life and work of Jan Jesensky (1566-1621), the physician of a dying time.
AB  - Jan Jesensky (Johannes Jessenius) ranks among the outstanding Renaissance
      polymaths of Central Europe. Stemming from Horne Jaseno (present-day Slovakia),
      born in Wroclaw (Poland), he studied philosophy and medicine in Wittenberg,
      Leipzig (Germany) and Padua (Italy), worked in Wroclaw, Wittenberg, Prague (Czech
      Republic) and Vienna (Austria), and was executed in Prague. He was influenced by
      and himself impacted upon a large area of the pre-30-year-war Europe science,
      learning and politics. The year 2011 marked the 410th anniversary of the
      publication of his famous description of the public dissection performed in
      Prague, as well as the 390th anniversary of his death. His scientific and
      editorial work covers not only anatomy but also surgery, internal medicine,
      infectious diseases and even philosophy and poetry. Moreover, he was very active
      as University Rector (in both Wittenberg and Prague) and also as politician of
      the Protestant fraction in Bohemia, which unfortunately led to his violent death.
      He was an excellent promoter of his own person and work and he understood and
      exerted dexterously the power of publicity. 

PMID- 24585764
TI  - Sir Harry Sinderson Pasha and Iraq's first medical school.
AB  - During the early twentieth century, the medical status of Mesopotamia, later
      Iraq, was very bad due to the lack of sanitation and recurrent epidemics and it
      was rife with endemic diseases including bilharziasis, tuberculosis and malaria.
      Medical care was poor, with few hospitals and doctors. The condition improved
      slowly with the return of a few Iraqi doctors who trained outside Iraq, in
      Turkey, Syria and Lebanon, and with the arrival of British Medical personnel,
      during and after the First World War, principally Sir Harry Sinderson who was one
      of the most influential figures in recent Iraqi medical and political history. He
      had the distinctive role of being one of the founders and the Dean of the first
      Iraqi medical college. During his service until his retirement in 1946 he
      achieved, with tireless effort, exceptionally high standards and brought fame and
      prestige to the new medical college in record time. He attained his goal of
      training at least 500 local doctors. 

PMID- 24585765
TI  - Thomas Paytherus (1752-1828): Entrepreneurial surgeon-apothecary and ardent
      Jennerian.
AB  - Thomas Paytherus was born in Fownhope and apprenticed in Gloucester. He practised
      there and in Ross-on-Wye where he and Edward Jenner undertook an autopsy on a
      patient with angina that they linked causally to coronary artery ossification. In
      1794 Paytherus moved to London and opened a highly successful pharmacy that he
      later sold to his partners Savory and Moore. Paytherus was among those who
      advised Jenner on the publication of his work on vaccination. Then he acted as an
      intermediary in the dispute between Jenner and Ingen-Housz and also alerted
      Jenner to Pearson's claims as a pioneer of vaccination. In 1800 he published a
      detailed analysis of the dispute between Jenner and Woodville whose patients had
      developed variola-like lesions following vaccination. Their correspondence shows
      that Paytherus, Jenner and their families remained firm friends. Paytherus and
      his family moved to Abergavenny where he died in 1828. 

PMID- 24585766
TI  - Arthur Rainsford Mowlem (1902-1986), plastic surgeon.
AB  - Arthur Rainsford Mowlem, the junior of the 'big four' plastic surgeons, with
      Harold Delf Gillies, Thomas Pomfret Kilner and Archibald Hector McIndoe, came to
      prominence managing casualties of the Second World War. Rainsford Mowlem's
      ancestor was John Mowlem, the creator of the construction firm. Rainsford worked
      his passage to the United Kingdom from New Zealand in 1927 and did not return to
      New Zealand but retired at the age of 60 to enjoy 23 more years in Spain. He was
      the driving force between 1934 and 1939 at the Plastic Surgery Unit at St James's
      Hospital, Balham, and instigated the North London Plastic Surgery Unit at Hill
      End, St Albans, from 1939 to 1953 and subsequently developed the Unit after
      moving to Mount Vernon Hospital, Northwood, Middlesex. After successfully hosting
      the International Meeting of Plastic Surgeons in London in 1959, he received
      recognition and honours in America but soon afterwards he surprised colleagues by
      retiring in 1962. Despite his significant contributions, he did not receive
      national honours but his life outside surgery was active including Trusteeship of
      the Mowlem Estate at Swanage in Dorset for 40 years. 

PMID- 24585767
TI  - The continuing influence of William Smellie (1697-1763) in Japan during the early
      Meiji Period (1868-1880s).
AB  - From the second half of the 18th century, Japanese obstetricians incorporated
      William Smellie's Anatomical Tables in their publications. The translation and
      explanation of an obstetrical print from 1880 indicates that Smellie's influence
      continued during the early Meiji period, a transition period characterized by a
      combination of western knowledge and traditional medical thoughts from the Edo
      period (1603-1868). 

PMID- 24585770
TI  - Cytological features of mammary analogue secretory carcinoma of salivary gland:
      fine-needle aspiration of seven cases.
AB  - Mammary analogue secretory carcinoma (MASC) is a recently described salivary
      gland neoplasm that is defined by ETV6-NTRK3 gene fusion. There have been few
      case reports on the cytopathologic features of MASC to date. We examined the
      clinicopathological and cytological features of seven cases of MASC defined by RT
      PCR analysis of the ETV6-NTRK3 fusion gene. The cases occurred in three men and
      four women aged between 39 and 68 years, with a mean of 51.6 years. In five of
      these seven cases, the tumor involved the parotid gland. Histologically, all
      cases displayed predominantly microcystic patterns, often a mixture of follicular
      and papillary-cystic structures. All tumors were immunoreactive for mammaglobin,
      S-100 protein, and vimentin. Available fine-needle aspiration cytology smears
      were cellular and exhibited many loosely cohesive syncytial clusters or isolated
      cells. Many histiocytes, some of which contained hemosiderin pigments, and
      variously shaped mucinous material were evident in the background or within the
      epithelial clusters. The majority of cases showed small to medium-sized
      follicular structures with secreted materials. Papillary clusters were
      occasionally found. Tumor cells exhibited small to medium-sized round to oval
      nuclei, with a smooth contour and indistinct or small nucleoli, and vacuolated
      cytoplasm. No tumor cells had obvious intracytoplasmic zymogen granules. It
      appeared that clusters of small to medium-sized follicular and papillary
      configurations consisting of bland tumor cells with vacuolated cytoplasm, but
      lack of intracytoplasmic zymogen granules, in a mucinous or hemosiderin-laden
      histiocyte-rich background, were a characteristic cytological feature highly
      suggestive of MASC.

PMID- 24585771
TI  - Wrangling Galaxy's reference data.
AB  - The Galaxy platform has developed into a fully featured collaborative workbench,
      with goals of inherently capturing provenance to enable reproducible data
      analysis, and of making it straightforward to run one's own server. However, many
      Galaxy platform tools rely on the presence of reference data, such as alignment
      indexes, to function efficiently. Until now, the building of this cache of data
      for Galaxy has been an error-prone manual process lacking reproducibility and
      provenance. The Galaxy Data Manager framework is an enhancement that changes the
      management of Galaxy's built-in data cache from a manual procedure to an
      automated graphical user interface (GUI) driven process, which contains the same
      openness, reproducibility and provenance that is afforded to Galaxy's analysis
      tools. Data Manager tools allow the Galaxy administrator to download, create and
      install additional datasets for any type of reference data in real time.
      AVAILABILITY AND IMPLEMENTATION: The Galaxy Data Manager framework is implemented
      in Python and has been integrated as part of the core Galaxy platform. Individual
      Data Manager tools can be defined locally or installed from a ToolShed, allowing
      the Galaxy community to define additional Data Manager tools as needed, with full
      versioning and dependency support.

PMID- 24585772
TI  - Cytomorphological features of atypical teratoid/rhabdoid tumor: an account of 12
      years' experience.
AB  - Atypical teratoid rhabdoid tumor (AT/RT), an aggressive neoplasm mostly affecting
      young children, is characterized by rhabdoid cells together with epithelial,
      mesenchymal and primitive differentiation. Diagnosing AT/RT in intraoperative
      consultation and cerebrospinal fluid (CSF) samples may therefore pose problems.
      Fourteen immunohistochemically proven AT/RTs diagnosed between 2000 and 2012 were
      collected. Material consisted of squash smears prepared during intraoperative
      consultation (thirteen) and CSF smears (three). MGG-stained CSF smears and H&E
      stained squash smears were reviewed by a neuropathologist and a cytopathologist.
      The intraoperative diagnoses were based on squash preparations and 3 out of 13
      were consistent with AT/RT, 4 were considered medulloblastoma/primitive
      neuroectodermal tumors (PNET), 3 were deferred to paraffin section for tumor
      typing, and another 3 were misdiagnosed as ependymoma, germinoma and malignant
      glioma. Morphological assessment of intraoperative squash preparations showed
      that AT/RTs can have a mixture of pseudopapillary and diffuse smearing patterns.
      Cytomorphologic features consisted of characteristic rhabdoid cells (8/9);
      primitive appearing cells with a high nuclear to cytoplasmic ratio (7/9); bi
      /multinucleated cells (3/9); rare necrosis/apoptosis and mitoses. Three CSF
      smears showed high cellularity and inclusion-bearing large cells. These cells are
      characterized by reniform/oval, eccentrically placed nuclei with cytoplasmic
      perinuclear light stained areas which are not seen in intraoperative squash
      preparations. Differential diagnosis of AT/RT in cytology involves
      medulloblastoma/PNET, ependymoma, glioma and germinoma among all others.
      Overlapping features of AT/RT with entities in differential diagnosis are
      discussed with a special emphasis of rhabdoid cells being the strongest feature
      to aid in reaching the diagnosis of AT/RT.

PMID- 24585773
TI  - Distinct adaptor proteins assist exit of Kre2-family proteins from the yeast ER.
AB  - The Svp26 protein of S. cerevisiae is an ER- and Golgi-localized integral
      membrane protein with 4 potential membrane-spanning domains. It functions as an
      adaptor protein that facilitates the ER exit of Ktr3, a mannosyltransferase
      required for biosynthesis of O-linked oligosaccharides, and the ER exit of Mnn2
      and Mnn5, mannosyltransferases, which participate in the biosynthesis of N-linked
      oligosaccharides. Ktr3 belongs to the Kre2 family, which consists of 9 members of
      type-II membrane proteins sharing sequence similarities. In this report, we
      examined all Kre2 family members and found that the Golgi localizations of two
      others, Kre2 and Ktr1, were dependent on Svp26 by immunofluorescence microscopy
      and cell fractionations in sucrose density gradients. We show that Svp26
      functions in facilitating the ER exit of Kre2 and Ktr1 by an in vitro COPII
      budding assay. Golgi localization of Ktr4 was not dependent on Svp26. Screening
      null mutants of the genes encoding abundant COPII membrane proteins for those
      showing mislocalization of Ktr4 in the ER revealed that Erv41 and Erv46 are
      required for the correct Golgi localization of Ktr4. We provide biochemical
      evidence that the Erv41-Erv46 complex functions as an adaptor protein for ER exit
      of Ktr4. This is the first demonstration of the molecular function of this
      evolutionally conserved protein complex. The domain switching experiments show
      that the lumenal domain of Ktr4 is responsible for recognition by the Erv41-Erv46
      complex. Thus, ER exit of Kre2-family proteins is dependent on distinct adaptor
      proteins and our results provide new insights into the traffic of Kre2-family
      mannosyltransferases. 

PMID- 24585774
TI  - Wild bees preferentially visit Rudbeckia flower heads with exaggerated
      ultraviolet absorbing floral guides.
AB  - Here, we report on the results of an experimental study that assessed the
      visitation frequency of wild bees to conspecific flowers with different sized
      floral guides. UV absorbent floral guides are ubiquitous in Angiosperms, yet
      surprisingly little is known about conspecific variation in these guides and very
      few studies have evaluated pollinator response to UV guide manipulation. This is
      true despite our rich understanding about learning and color preferences in bees.
      Historical dogma indicates that flower color serves as an important long-range
      visual signal allowing pollinators to detect the flowers, while floral guides
      function as close-range signals that direct pollinators to a reward. We initiated
      the work presented here by first assessing the population level variation in UV
      absorbent floral guides for conspecific flowers. We assessed two species,
      Rudbeckia hirta and R. fulgida. We then used several petal cut-and-paste
      experiments to test whether UV floral guides can also function to attract
      visitors. We manipulated floral guide size and evaluated visitation frequency. In
      all experiments, pollinator visitation rates were clearly associated with floral
      guide size. Diminished floral guides recruited relatively few insect visitors.
      Exaggerated floral guides recruited more visitors than smaller or average sized
      guides. Thus, UV floral guides play an important role in pollinator recruitment
      and in determining the relative attractiveness of conspecific flower heads.
      Consideration of floral guides is therefore important when evaluating the overall
      conspicuousness of flower heads relative to background coloration. This work
      raises the issue of whether floral guides serve as honest indicators of reward,
      since guide size varies in nature for conspecific flowers at the same
      developmental stage and since preferences for larger guides were found. To our
      knowledge, these are the first cut-and-paste experiments conducted to examine
      whether UV absorbent floral guides affect visitation rates and pollinator
      preference. 

PMID- 24585775
TI  - A talin mutant that impairs talin-integrin binding in platelets decelerates
      alphaIIbbeta3 activation without pathological bleeding.
AB  - Tight regulation of integrin affinity is critical for hemostasis. A final step of
      integrin activation is talin binding to 2 sites within the integrin beta
      cytoplasmic domain. Binding of talin to a membrane-distal NPxY sequence
      facilitates a second, weaker interaction of talin with an integrin membrane
      proximal region (MPR) that is critical for integrin activation. To test the
      functional significance of these distinct interactions on platelet function in
      vivo, we generated knock-in mice expressing talin1 mutants with impaired capacity
      to interact with the beta3 integrin MPR (L325R) or NPLY sequence (W359A). Both
      talin1(L325R) and talin1(W359A) mice were protected from experimental thrombosis.
      Talin1(L325R) mice, but not talin(W359A) mice, exhibited a severe bleeding
      phenotype. Activation of alphaIIbbeta3 was completely blocked in talin1(L325R)
      platelets, whereas activation was reduced by approximately 50% in talin1(W359A)
      platelets. Quantitative biochemical measurements detected talin1(W359A) binding
      to beta3 integrin, albeit with a 2.9-fold lower affinity than wild-type talin1.
      The rate of alphaIIbbeta3 activation was slower in talin1(W359A) platelets, which
      consequently delayed aggregation under static conditions and reduced thrombus
      formation under physiological flow conditions. Together our data indicate that
      reduction of talin-beta3 integrin binding affinity results in decelerated
      alphaIIbbeta3 integrin activation and protection from arterial thrombosis without
      pathological bleeding.

PMID- 24585777
TI  - Stromal interaction molecule 1 is essential for normal cardiac homeostasis
      through modulation of ER and mitochondrial function.
AB  - The endoplasmic reticulum (ER) Ca(2+) sensor stromal interaction molecule 1
      (STIM1) has been implicated as a key mediator of store-dependent and store
      independent Ca(2+) entry pathways and maintenance of ER structure. STIM1 is
      present in embryonic, neonatal, and adult cardiomyocytes and has been strongly
      implicated in hypertrophic signaling; however, the physiological role of STIM1 in
      the adult heart remains unknown. We, therefore, developed a novel cardiomyocyte
      restricted STIM1 knockout ((cr)STIM1-KO) mouse. In cardiomyocytes isolated from
      (cr)STIM1-KO mice, STIM1 expression was reduced by ~92% with no change in the
      expression of related store-operated Ca(2+) entry proteins, STIM2, and Orai1.
      Immunoblot analyses revealed that (cr)STIM1-KO hearts exhibited increased ER
      stress from 12 wk, as indicated by increased levels of the transcription factor
      C/EBP homologous protein (CHOP), one of the terminal markers of ER stress.
      Transmission electron microscopy revealed ER dilatation, mitochondrial
      disorganization, and increased numbers of smaller mitochondria in (cr)STIM1-KO
      hearts, which was associated with increased mitochondrial fission. Using serial
      echocardiography and histological analyses, we observed a progressive decline in
      cardiac function in (cr)STIM1-KO mice, starting at 20 wk of age, which was
      associated with marked left ventricular dilatation by 36 wk. In addition, we
      observed the presence of an inflammatory infiltrate and evidence of cardiac
      fibrosis from 20 wk in (cr)STIM1-KO mice, which progressively worsened by 36 wk.
      These data demonstrate for the first time that STIM1 plays an essential role in
      normal cardiac function in the adult heart, which may be important for the
      regulation of ER and mitochondrial function.

PMID- 24585776
TI  - Emerging roles for platelets as immune and inflammatory cells.
AB  - Despite their small size and anucleate status, platelets have diverse roles in
      vascular biology. Not only are platelets the cellular mediator of thrombosis, but
      platelets are also immune cells that initiate and accelerate many vascular
      inflammatory conditions. Platelets are linked to the pathogenesis of inflammatory
      diseases such as atherosclerosis, malaria infection, transplant rejection, and
      rheumatoid arthritis. In some contexts, platelet immune functions are protective,
      whereas in others platelets contribute to adverse inflammatory outcomes. In this
      review, we will discuss platelet and platelet-derived mediator interactions with
      the innate and acquired arms of the immune system and platelet-vessel wall
      interactions that drive inflammatory disease. There have been many recent
      publications indicating both important protective and adverse roles for platelets
      in infectious disease. Because of this new accumulating data, and the fact that
      infectious disease continues to be a leading cause of death globally, we will
      also focus on new and emerging concepts related to platelet immune and
      inflammatory functions in the context of infectious disease. 

PMID- 24585778
TI  - Length-dependent activation is modulated by cardiac troponin I bisphosphorylation
      at Ser23 and Ser24 but not by Thr143 phosphorylation.
AB  - Frank-Starling's law reflects the ability of the heart to adjust the force of its
      contraction to changes in ventricular filling, a property based on length
      dependent myofilament activation (LDA). The threonine at amino acid 143 of
      cardiac troponin I (cTnI) is prerequisite for the length-dependent increase in
      Ca(2+) sensitivity. Thr143 is a known target of protein kinase C (PKC) whose
      activity is increased in cardiac disease. Thr143 phosphorylation may modulate
      length-dependent myofilament activation in failing hearts. Therefore, we
      investigated if pseudo-phosphorylation at Thr143 modulates length dependence of
      force using troponin exchange experiments in human cardiomyocytes. In addition,
      we studied effects of protein kinase A (PKA)-mediated cTnI phosphorylation at
      Ser23/24, which has been reported to modulate LDA. Isometric force was measured
      at various Ca(2+) concentrations in membrane-permeabilized cardiomyocytes
      exchanged with recombinant wild-type (WT) troponin or troponin mutated at the PKC
      site Thr143 or Ser23/24 into aspartic acid (D) or alanine (A) to mimic
      phosphorylation and dephosphorylation, respectively. In troponin-exchanged donor
      cardiomyocytes experiments were repeated after incubation with exogenous PKA.
      Pseudo-phosphorylation of Thr143 increased myofilament Ca(2+) sensitivity
      compared with WT without affecting LDA in failing and donor cardiomyocytes.
      Subsequent PKA treatment enhanced the length-dependent shift in Ca(2+)
      sensitivity after WT and 143D exchange. Exchange with Ser23/24 variants
      demonstrated that pseudo-phosphorylation of both Ser23 and Ser24 is needed to
      enhance the length-dependent increase in Ca(2+) sensitivity. cTnI pseudo
      phosphorylation did not alter length-dependent changes in maximal force. Thus
      phosphorylation at Thr143 enhances myofilament Ca(2+) sensitivity without
      affecting LDA, while Ser23/24 bisphosphorylation is needed to enhance the length
      dependent increase in myofilament Ca(2+) sensitivity.

PMID- 24585779
TI  - Hyperhomocysteinemia attenuates angiogenesis through reduction of HIF-1alpha and
      PGC-1alpha levels in muscle fibers during hindlimb ischemia.
AB  - Hyperhomocysteinemia (HHcy) is associated with elderly frailty, skeletal muscle
      injury and malfunction, reduced vascular integrity and function, and mortality.
      Although HHcy has been implicated in the impairment of angiogenesis after
      hindlimb ischemia in murine models, the underlying mechanisms are still unclear.
      We hypothesized that HHcy compromises skeletal muscle perfusion, collateral
      formation, and arteriogenesis by diminishing postischemic vasculogenic responses
      in muscle fibers. To test this hypothesis, we created femoral artery ligation in
      wild-type and heterozygous cystathionine beta-synthase (CBS(+/-)) mice (a model
      for HHcy) and assessed tissue perfusion, collateral vessel formation, and
      skeletal muscle function using laser-Doppler perfusion imaging, barium
      angiography, and fatigue tests. In addition, we assessed postischemic levels of
      VEGF and levels of its muscle-specific regulators: hypoxia-inducible factor (HIF)
      1alpha and peroxisome proliferator-activated receptor-gamma coactivator (PGC)
      1alpha. The observations indicated dysregulation of VEGF, HIF-1alpha, and PGC
      1alpha levels in ischemic skeletal muscles of CBS(+/-) mice. Concomitant with the
      reduced ischemic angiogenic responses, we also observed diminished leptin
      expression and attenuated Akt signaling in ischemic muscle fibers of CBS(+/-)
      mice. Moreover, there was enhanced atrogene, ubiquitin ligases that conjugate
      proteins for degradation during muscle atrophy, transcription, and reduced muscle
      function after ischemia in CBS(+/-) mice. These results suggest that HHcy
      adversely affects muscle-specific ischemic responses and contributes to muscle
      frailty.

PMID- 24585780
TI  - Electroacupuncture improves cardiac function and remodeling by inhibition of
      sympathoexcitation in chronic heart failure rats.
AB  - Chronic heart failure (CHF) is responsible for significant morbidity and
      mortality worldwide, mainly as a result of neurohumoral activation. Acupuncture
      has been used to treat a wide range of diseases and conditions. In this study, we
      investigated the effects of electroacupuncture (EA) on the sympathetic nerve
      activity, heart function, and remodeling in CHF rats after ligation of the left
      anterior descending coronary artery. CHF rats were randomly selected to EA and
      control groups for acute and chronic experiments. In the acute experiment, both
      the renal sympathetic nerve activity and cardiac sympathetic afferent reflex
      elicited by epicardial application of capsaicin were recorded. In the chronic
      experiment, we performed EA for 30 min once a day for 1 wk to test the long-term
      EA effects on heart function, remodeling, as well as infarct size in CHF rats.
      The results show EA significantly decreased the renal sympathetic nerve activity
      effectively, inhibited cardiac sympathetic afferent reflex, and lowered the blood
      pressure of CHF rats. Treating CHF rats with EA for 1 wk dramatically increased
      left ventricular ejection fraction and left ventricular fraction shortening,
      reversed the enlargement of left ventricular end-systolic dimension and left
      ventricular end-diastolic dimension, and shrunk the infarct size. In this
      experiment, we demonstrated EA attenuates sympathetic overactivity. Additionally,
      long-term EA improves cardiac function and remodeling and reduces infarct size in
      CHF rats. EA is a novel and potentially useful therapy for treating CHF.

PMID- 24585782
TI  - Strategy to avoid patient-prosthesis mismatch: aortic root enlargement.
AB  - BACKGROUND: The choice of a valve with an effective orifice area matching the
      body surface area and providing efficient hemodynamics is an important factor
      affecting mortality and morbidity in patients undergoing aortic valve
      replacement. PATIENTS AND METHODS: Our preventative strategy was to implant a
      larger prosthetic valve by aortic root enlargement using the Nunez procedure in
      17 patients between February 2010 and January 2011. The decision to enlarge the
      aortic root was taken when the 19-mm sizer could not be negotiated easily through
      the aortic root, or on the basis of body surface area of the patient or type of
      prosthesis available. RESULTS: Postoperative reductions in peak and mean pressure
      gradients across aortic valve of 12.8-16.5 and 10.2-12.6 mm Hg, respectively,
      were observed. Postoperative effective orifice areas of the aortic valves were
      1.1-1.5 cm(2). By upsizing the aortic valve, we were able to eliminate patient
      prosthesis mismatch in 5 patients, and reduce severe patient-prosthesis mismatch
      to moderate in 11. CONCLUSION: Aortic root enlargement is a safe procedure.
      Therefore, cardiac surgeons should not be reluctant to enlarge the aortic root
      with an autologous pericardial patch to permit implantation of an adequate size
      of aortic valve prosthesis, with minimal additional aortic crossclamp time and no
      added cost.

PMID- 24585781
TI  - Automated analysis of contractile force and Ca2+ transients in engineered heart
      tissue.
AB  - Contraction and relaxation are fundamental aspects of cardiomyocyte functional
      biology. They reflect the response of the contractile machinery to the systolic
      increase and diastolic decrease of the cytoplasmic Ca(2+) concentration. The
      analysis of contractile function and Ca(2+) transients is therefore important to
      discriminate between myofilament responsiveness and changes in Ca(2+)
      homeostasis. This article describes an automated technology to perform sequential
      analysis of contractile force and Ca(2+) transients in up to 11 strip-format,
      fibrin-based rat, mouse, and human fura-2-loaded engineered heart tissues (EHTs)
      under perfusion and electrical stimulation. Measurements in EHTs under increasing
      concentrations of extracellular Ca(2+) and responses to isoprenaline and
      carbachol demonstrate that EHTs recapitulate basic principles of heart tissue
      functional biology. Ca(2+) concentration-response curves in rat, mouse, and human
      EHTs indicated different maximal twitch forces (0.22, 0.05, and 0.08 mN in rat,
      mouse, and human, respectively; P < 0.001) and different sensitivity to external
      Ca(2+) (EC50: 0.15, 0.39, and 1.05 mM Ca(2+) in rat, mouse, and human,
      respectively; P < 0.001) in the three groups. In contrast, no difference in
      myofilament Ca(2+) sensitivity was detected between skinned rat and human EHTs,
      suggesting that the difference in sensitivity to external Ca(2+) concentration is
      due to changes in Ca(2+) handling proteins. Finally, this study confirms that
      fura-2 has Ca(2+) buffering effects and is thereby changing the force response to
      extracellular Ca(2+). 

PMID- 24585783
TI  - Relationship between stress and coronary heart disease.
AB  - BACKGROUND: Coronary heart disease is the leading cause of death worldwide and
      accounts for 13.7% of deaths in countries like Pakistan. Its association with
      stress has not been well considered in our setup. Patients with coronary artery
      disease admitted for coronary artery bypass grafting may have a high prevalence
      of stress that might increase the risk of adverse outcomes. METHODS: 60 patients
      with coronary artery disease admitted to the Civil Hospital Karachi for coronary
      artery bypass graft surgery from January 1 to March 31, 2012, were evaluated
      using a stress evaluation scale. RESULTS: Stress of varying degrees was found to
      be a significant independent risk factor in patients with coronary heart disease.
      Analysis of our collected sample of patients with stress showed 60% with high
      stress (p = 0.025) and 36.7% moderate stress (p = 0.0025). An appreciable
      relationship was found between stress and patient age, sex, body mass index,
      blood group, and the incidence of myocardial infarction. CONCLUSION: Our study
      found evidence of an independent causative association between psychological
      stress and coronary heart disease, of a similar order to the more conventional
      coronary heart disease risk factors.

PMID- 24585784
TI  - Recombinant activated factor VII in cardiac surgery: single-center experience.
AB  - BACKGROUND: The widespread off-label use of recombinant activated factor VII for
      the control of refractory postoperative hemorrhage continues despite a warning
      from the Food and Drug Administration. Although effective in reducing the need
      for transfusion of blood and blood products, safety concerns still prevail.
      OBJECTIVE: To compare the dosing and efficacy of recombinant activated factor VII
      between pediatric and adult patients, and in the operating room and intensive
      care unit. METHODS: The records of 69 patients (33 children and 36 adults) who
      underwent cardiovascular surgery and received recombinant activated factor VII
      were reviewed retrospectively. The dose of recombinant activated factor VII,
      mediastinal drainage, use of blood and blood products, incidence of thrombosis,
      and 28-day mortality were studied. RESULTS: the efficacy of recombinant activated
      factor VII was comparable in adults and children, despite the lower dose in
      adults. Prophylactic use of recombinant activated factor VII decreased the
      incidence of mediastinal exploration and the duration of intensive care unit
      stay. A 4.3% incidence of thrombotic complications was observed in this study.
      CONCLUSION: The efficacious dose of recombinant activated factor VII is much less
      in adults compared to children. Prophylactic use of recombinant activated factor
      VII decreases the dose required, the incidence of mediastinal exploration, and
      intensive care unit stay, with no survival benefit.

PMID- 24585785
TI  - Role of video-assisted thoracoscopy in the management of stroke.
AB  - OBJECTIVE: To evaluate the role of surgery (anterior thoracotomy versus video
      assisted thoracoscopy) in avoidance of stroke by obliteration of the left atrial
      appendage in patients with chronic nonrheumatic atrial fibrillation. METHODS: In
      a prospective study, 58 patients (35 men and 23 women, aged 62 +/- 13.2 years)
      with chronic nonrheumatic atrial fibrillation were divided into 2 groups: group A
      was 29 patients who underwent an anterior thoracotomy, and group B was 29
      patients who had video-assisted thoracoscopic obliteration of the left atrial
      appendage. All patients were followed up for at least 2 years. RESULTS: The 2
      groups were well matched for age, sex, and comorbidities. No stroke was observed
      in either group. Operative time was significantly longer in group B. There was no
      intraoperative or postoperative complication, except for 2 cases of superficial
      wound infection in group A. CONCLUSIONS: In chronic atrial fibrillation,
      prophylactic left atrial appendage exclusion is suggested to prevent occurrence
      of stroke, which can be achieved by a surgical or thoracoscopic approach, but a
      video-assisted thoracoscopic approach is effective, less invasive, and avoids the
      complications of a surgical approach.

PMID- 24585786
TI  - Dynamic evaluation of the loop technique using the U-Clip.
AB  - BACKGROUND: We set out to evaluate mitral valve repair with the loop technique
      under dynamic conditions, using a U-Clip to anchor the loop unit to a papillary
      muscle. METHODS: Mitral valve prolapse was artificially developed by resecting 4
      chordae tendineae of a resected porcine heart. The loop unit was anchored to the
      papillary muscle using U-Clips. Each chordal loop was fixed on the prolapsed
      leaflet. A roller pump perfused the left ventricle. The left ventricular pressure
      was maintained at 250 mm Hg. Morphological assessment of the loop reconstruction
      was performed using an endoscope. RESULTS: 10 independent chordal reconstructions
      were performed. In all cases, the loop unit remained anchored against pressures
      exceeding 250 mm Hg. Upon increasing the water filling volume, rupture of a
      chorda tendinea occurred in 7 cases, rupture of the papillary muscle occurred in
      2 cases, and left ventricle rupture occurred in 1 case. In all rupture cases, the
      loop unit remained anchored to the papillary muscle. CONCLUSION: This dynamic
      evaluation of the loop technique using U-Clips to anchor the loop unit to a
      papillary muscle showed that the loop technique using U-Clips is a safe method.

PMID- 24585787
TI  - EuroSCORE vs. EuroSCORE II vs. Society of Thoracic Surgeons risk algorithm.
AB  - INTRODUCTION: This study presents a validation series for EuroSCORE II compared
      with the previous additive and logistic EuroSCORE and the Society of Thoracic
      Surgeons risk prediction algorithm. PATIENTS AND METHODS: Clinical data of 2004
      patients undergoing isolated coronary artery bypass surgery between 2006 and 2010
      were retrospectively collected and individual expected risks of death were
      calculated by all 3 risk prediction algorithms. Performance of these risk
      algorithms was evaluated in terms of discrimination and calibration. RESULTS:
      There were 76 deaths (3.8%) among 2004 patients. The mean EuroSCORE II predicted
      mortality was 3.72% +/- 5.11%, additive EuroSCORE was 4.35%  +/- 3.65% and
      logistic EuroSCORE was 6.41%  +/- 10.06%. The additive EuroSCORE was better than
      EuroSCORE II in terms of both discrimination and calibration (C-statistic 0.866
      and Hosmer-Lemeshow p value 0.230 vs. C-statistic 0.836 and Hosmer-Lemeshow p
      value 0.013 for EuroSCORE II). In a subset of 380 patients, we compared EuroSCORE
      II with the Society of Thoracic Surgeons risk prediction. Actual mortality was
      2.89%. Predicted mortality by EuroSCORE II was 4.27%  +/- 5.22% and Society of
      Thoracic Surgeons risk prediction was 2.30%  +/- 4.16%. The area under the curve
      was 0.759 for EuroSCORE II and 0.898 for the Society of Thoracic Surgeons risk
      prediction, whereas the Hosmer-Lemeshow p value was 0.267 for EuroSCORE II and
      0.981 for Society of Thoracic Surgeons risk prediction. CONCLUSION: The Society
      of Thoracic Surgeons risk prediction algorithm is a better risk assessment tool
      compared to additive and logistic EuroSCORE and EuroSCORE II in Pakistani
      patients.

PMID- 24585789
TI  - Descending necrotizing mediastinitis below the tracheal carina.
AB  - BACKGROUND: Descending necrotizing mediastinitis is a dreadful disease with a
      high mortality rate, particularly when below the tracheal carina. This study
      describes the epidemiologic, clinical, and paraclinical features of patients
      treated for this condition. METHODS: We performed a single-center retrospective
      descriptive review of 60 patients with descending necrotizing mediastinitis below
      the tracheal carina, who were treated during a 7-year period, the largest study
      in the last 50 years. Demographic, clinical, paraclinical, and therapeutic
      variables were analyzed. RESULTS: 43 (71.7%) patients were male. The mean age was
      41.2 +/- 14.7 years. Mean hospital length of stay was 25.0 +/- 19.8 days.
      Comorbidities were present in 46.7% of patients, diabetes mellitus being the most
      common. Odontogenic infections (45%) were the most frequent source of descending
      necrotizing mediastinitis. Cultures showed Gram-negative bacilli in 68.3%, Gram
      positive cocci in 38.3%, and fungi in 6.7%. Mortality was 35% (21 patients); risk
      factors for mortality were age (>35 years), diabetes mellitus among other
      comorbidities, and associated complications. CONCLUSIONS: In this low
      socioeconomic status patient population, descending necrotizing mediastinitis
      below the carina causes high morbidity and mortality, the latter particularly
      associated with age, complications, diabetes mellitus and other comorbidities.

PMID- 24585788
TI  - Efficacy of arginine supplementation for the treatment of air leakage.
AB  - BACKGROUND: Recently, the role of the amino acid arginine in wound healing has
      been emphasized. We studied whether postoperative enteral arginine
      supplementation can contribute to the resolution of prolonged air leakage after
      lung resections. METHODS: 42 patients undergoing lung resection at our
      institutions from 2009 to 2012 were enrolled in this study. In these patients,
      continuous air leakage in the expiratory phase was identified on the day of
      surgery and on the following day. The patients were divided into 2 groups; the
      first group included 21 patients consuming 3 packs of an arginine supplement
      beverage daily postoperatively, and the second group (control) included 21
      patients who did not consume any additional supplements. The durations of air
      leakage and chest tube drainage were compared between the two groups. RESULTS:
      The mean durations of air leakage and chest tube drainage were shorter in the
      arginine supplementation group (4.4 vs. 6.7 days, p = 0.010; 6.5 vs. 8.3 days, p
      = 0.042, respectively). CONCLUSION: Postoperative enteral arginine
      supplementation may contribute to stopping air leaks after lung surgery.

PMID- 24585790
TI  - Missed pulmonary metastasis.
AB  - OBJECTIVE: To assess the rate of detection of pulmonary nodules on preoperative
      computed tomography, based on intraoperative palpation of non-imaged pulmonary
      nodules, in patients who underwent thoracotomy for metastasectomy with bimanual
      lung palpation. METHODS: A retrospective study carried out on all cases of
      pulmonary metastasectomy performed in King Faisal Specialist Hospital and
      Research Center over a 10-year period (2001-2011). The number of nodules detected
      on preoperative computed tomography by a radiologist was compared with the number
      of nodules identified on pathology. Resected pulmonary nodules were classified to
      benign or malignant. Secondary outcomes were operative approach and primary
      malignancy. RESULTS: 215 metastasectomies were performed by thoracotomy. The
      incidence of nodules that were not imaged preoperatively was 36% (41% of
      mesenchymal tumors, 28% of epithelial tumors). CONCLUSION: Metastasectomy by an
      open approach, which affords bimanual palpation of the entire lung, discovered
      ipsilateral non-imaged malignant pulmonary metastases in 36% of cases (41% of
      mesenchymal tumors).

PMID- 24585791
TI  - Thoracoscopic repair of pectus excavatum using different bar stabilizers versus
      open repair.
AB  - OBJECTIVES: To identify the preoperative characteristics and compare operative
      variables and postoperative outcomes in adult patients with pectus excavatum
      undergoing thoracoscopic repair using different bar stabilizers or open surgical
      repair. METHODS: 31 patients were randomly divided into 3 groups: group A was 9
      patients who underwent a modified Ravitch repair, group B was 11 patients who
      underwent video-assisted thoracoscopic repair using metal stabilizers, and group
      C was 11 patients who underwent video-assisted thoracoscopic repair using
      absorbable stabilizers. Preoperative, intraoperative, and postoperative variables
      and mortality were compared among groups. RESULTS: In all groups, preoperative
      variables were well-matched for age, sex, and Haller index. Operative time was
      significantly longer in group A. The postoperative length of hospital stay was
      significantly shorter in group A. Postoperative complications occurred in 7
      (22.6%) patients, mostly in groups B and C. All patients were satisfied with the
      cosmetic result. CONCLUSIONS: Repair of pectus excavatum in adult patients can be
      performed effectively either through an open surgical technique or thoracoscopy,
      with no intraoperative complications and excellent immediate results, but video
      assisted thoracoscopic repair using metallic or absorbable bar stabilizers gives
      a better cosmetic result; however, absorbable bar stabilizers are more vulnerable
      and break more easily than metal stabilizers.

PMID- 24585792
TI  - Neurogenic thoracic outlet syndrome treatment by the supraclavicular approach.
AB  - BACKGROUND: Thoracic outlet syndrome refers to compression of one or more of the
      neurovascular structures traversing the superior aperture of the thoracic cavity.
      OBJECTIVE: A symptom-based patient-directed questionnaire was used to evaluate
      the outcome of the supraclavicular approach for treatment of neurogenic thoracic
      outlet syndrome. PATIENTS AND METHODS: A prospective study was performed between
      April 2007 and October 2010. During this period, 97 patients in different age
      groups, with signs and symptoms of thoracic outlet syndrome, were surgically
      treated by the supraclavicular approach. The patients were aged between 14 and 60
      years (mean 32.5 years), and the majority were female (89.69%). Surgery was
      performed on the left side in 52 patients and on the right side in 48, including
      3 who had bilateral operations. The median follow-up was 11.2 months. RESULTS: In
      78% of the 100 operations, excellent improvement in symptoms was noted, there was
      partial improvement in 18%, and 4% resulted in no response. CONCLUSIONS: First
      rib resection remains an important and essential step in the management of the
      thoracic outlet syndrome, in the absence of bony abnormalities. The
      supraclavicular approach can be employed with minimal morbidity and an excellent
      outcome.

PMID- 24585793
TI  - Systolic anterior motion of the mitral valve masked by general anesthesia.
AB  - Systolic anterior motion of the mitral valve is usually associated with
      hypertrophic obstructive cardiomyopathy that results in left ventricular outflow
      tract obstruction. This is sometimes treated by volume loading or negative
      inotropics such as beta blockers. We report a rare case of dynamic systolic
      anterior motion of the mitral valve, in which a beta blocker did not diminish but
      anesthetic agents masked intraoperatively. The patient underwent mitral valve
      replacement, and left ventricular outflow tract obstruction was successfully
      treated. 

PMID- 24585794
TI  - Right origin of the circumflex artery and posterior aortic annulus enlargement.
AB  - We present the case of a patient who required posterior enlargement of the aortic
      annulus during aortic valve replacement in the presence of abnormal origin of the
      circumflex artery from the right coronary artery, with a retroaortic course.

PMID- 24585795
TI  - HeartWare left ventricular assist device thrombosis in aspirin non-responder.
AB  - Patient characteristics that increase the risk of continuous-flow left
      ventricular assist device thrombosis have not been well established. We report a
      case of HeartWare thrombosis in a patient with aspirin hyporesponsiveness, and
      discuss the role of platelet function testing in preventing this severe
      complication. There is a need for clinical trials determining optimal
      antiplatelet therapy in patients supported with left ventricular assist devices,
      and consensus regarding modification of antiplatelet therapy after device
      thrombosis. 

PMID- 24585796
TI  - Use of Rotaflow pump for left ventricular assist device bridging for 15 weeks.
AB  - Mechanical circulatory support systems have been described for short- and long
      term left ventricular assistance. We report the use of a Rotaflow centrifugal
      pump in a 55-year-old man with ischemic cardiomyopathy and severe left
      ventricular dysfunction. He was successfully bridged to transplantation with 15
      weeks of Rotaflow support, with no major adverse events.

PMID- 24585797
TI  - Emergency operation for aortic dissection with ischemic stroke.
AB  - A 68-year-old man lost consciousness while speaking. Computed tomography of the
      head revealed no hemorrhage or areas of hypodensity. Recombinant tissue
      plasminogen activator was administered. Neck duplex scanning showed dissecting
      intima of the right common carotid artery. Chest computed tomography disclosed
      Stanford type A aortic dissection. We performed emergency surgery because the
      right common carotid artery was severely stenosed. Despite 8 h of surgery due to
      coagulopathy, the patient was discharged without neurological deficits.

PMID- 24585798
TI  - Concomitant congenital heart defect repair and Nuss procedure for pectus
      excavatum.
AB  - The combination of complex congenital cardiac anomalies and pectus excavatum
      represents a technical challenge. Most concomitant repairs have been performed in
      adult patients. We report the uncomplicated concomitant repair of double-outlet
      right ventricle with absent pulmonary valve syndrome and the Nuss procedure for
      pectus excavatum in a 3-year-old child. 

PMID- 24585799
TI  - T-tube insertion for sclerotic subglottic stenosis.
AB  - T-tube insertion is effective treatment for subglottic stenosis, but it is
      generally difficult due to bending of the T-tube. In a 52-year-old woman with
      relapsing polychondritis, a T-tube was inserted after predilatation using Hegar
      dilators. We describe the details of our T-tube insertion methods for sclerotic
      subglottic stenosis.

PMID- 24585800
TI  - Large intrathoracic meningocele in a patient with neurofibromatosis type 1.
AB  - Intrathoracic meningocele associated with neurofibromatosis type 1 is quite rare.
      We report the case of a Chinese women with a 20-day history of right-sided chest
      pain and sense of pressure on the chest. Computed tomography and magnetic
      resonance imaging indicated a homogeneous thin-walled cystic mass in the right
      rear mediastinum, ranging from the 1st to 5th thoracic segments. Surgery was
      performed to removal the meningomyelocele pouches and shunt the cyst to the
      subarachnoid region. 

PMID- 24585801
TI  - Neurosurgical procedures, spinal nerve roots - one stage removal of thoracic dumb
      bell tumor: role of spinal evoked potential.
AB  - We report a rare case of benign thoracic dumb-bell tumor in the upper posterior
      mediastinum, which was successfully removed by posterolateral thoracotomy and
      foraminotomy, using intraoperative monitoring of spinal motor-evoked potentials.
      This technique has many advantages including minimal morbidity and mortality, a
      single incision, one-step complete resection with adequate exposure, spinal
      stabilization, avoidance of laminectomy, nerve root identification, and good
      predicted postoperative function. 

PMID- 24585802
TI  - Two cases of giant solitary fibrous tumor of the pleura: a not-so-rare tumor?
AB  - Solitary fibrous tumors of the pleura are rare intrathoracic neoplasms,
      especially in the giant form. The treatment of choice remains complete surgical
      resection which provides a benign clinical outcome. All patients need long-term
      follow-up due to the possibility of late recurrences. We describe 2 new cases of
      giant pleural fibrous tumor, which underwent resection via thoracotomy, and
      discuss the diagnostic and therapeutic modalities. 

PMID- 24585803
TI  - Porcelain heart: severely calcified pericardium due to Mycobacterium
      tuberculosis.

PMID- 24585804
TI  - Giant solitary fibrous tumor with pulmonary vein pseudothrombus.

PMID- 24585805
TI  - Complete resolution of type B aortic intramural hematoma with medical treatment.

PMID- 24585806
TI  - Acute type A intramural hematoma mimicking saccular aneurysm in aortography.

PMID- 24585807
TI  - Role of renal biomarkers as predictors of acute kidney injury in cardiac surgery.
AB  - Cardiac surgery is unique in using cardiopulmonary bypass in various clinical
      scenarios. Injury of vital organs is unavoidable in the perioperative period.
      Acute kidney injury is a consequence of the systemic inflammatory response after
      bypass, emboli, ischemia, and low cardiac output states, reportedly occurring in
      30%-40% of open heart surgeries. Acute kidney injury is associated with increased
      morbidity, mortality, and cost. Many preventive measures (off-pump procedures,
      decreased crossclamp time, pulsatile flow, adequate hydration) are taken in the
      perioperative period to avoid organ injury, but in vain. Traditionally, blood
      urea, serum creatinine, and creatinine clearance rate were applied for prediction
      of acute kidney injury. The recent emergence of biomarkers such as neutrophil
      gelatinase-associated lipocalin, cystatin C, liver-type fatty acid binding
      protein, interleukin-18, kidney injury molecule-1, and tetrahydrobiopterin have
      helped in detecting acute kidney injury long before the rise of serum creatinine.
      These biomarkers can also be used as tools for predicting therapeutic effects in
      acute kidney injury and for monitoring drug toxicity. This review consolidates
      the knowledge of biomarkers and their application in acute kidney injury
      management. 

PMID- 24585808
TI  - A variant "no-patch" technique for surgery of left ventricular aneurysms.
AB  - A variant "no-patch" technique for the surgical treatment of left ventricular
      aneurysms is described. The entire operation is performed using a single suture
      tied after the 2 encircling stitch adjustments and at the final external suture.
      Before the second encircling pursestring stitch, scar tissue circular plication
      is carried out. The final closure is completed by an out-out suture that ensures
      hemostasis. Finally, it is emphasized that the no-patch surgical strategy has the
      indirect advantage of saving time because the stitches are performed in a
      continuous manner. 

PMID- 24585809
TI  - Endovascular repair of intrathoracic ruptured Kommerell's diverticulum.

PMID- 24585810
TI  - Endovascular repair of ruptured Kommerell's diverticulum in a right aortic arch.

PMID- 24585811
TI  - Invest in primary care if you want to relieve emergency departments, GP leader
      says.

PMID- 24585812
TI  - Gynecologic examination of the prepubertal girl.

PMID- 24585813
TI  - Pediatric MRI of the brain: a primer.

PMID- 24585815
TI  - Complementary, holistic, and integrative medicine: utilization surveys of the
      pediatric literature.

PMID- 24585817
TI  - Von Willebrand disease.

PMID- 24585816
TI  - Index of suspicion. Case 1: fever, diarrhea, jaundice, and confusion in an 18
      year-old male. Case 2: severe anemia in a 6-month-old girl. Case 3: red urine in
      a 4-month-old boy.

PMID- 24585819
TI  - Visual diagnosis: 15-year-old girl with fever, extremity pain, and unusual rash.

PMID- 24585820
TI  - The slow, steady development of pediatric ethics committees, 1975-2013.

PMID- 24585821
TI  - Draft UK regulations for mitochondrial donation are published.

PMID- 24585822
TI  - Ageism in cancer care.

PMID- 24585823
TI  - Mind the gap.

PMID- 24585824
TI  - Hippocrates and the oath.

PMID- 24585825
TI  - Portraits in medical biography: Alexander Pope (1688-1744), poet, patient,
      celebrity.
AB  - Portraits are underused in the medical biographies of patients, yet they can
      illuminate health concerns and even health itself in many ways. Tying portraiture
      and medicine together analytically yields many insights into Pope's medical
      biography - from his response to satirical ridicule to his friends' concern for
      his health - without abandoning his portraits as works of 'art'. 

PMID- 24585826
TI  - A retrospective diagnosis of epilepsy in three historical figures: St Paul, Joan
      of Arc and Socrates.
AB  - It has been suggested that undiagnosed epilepsy profoundly influenced the lives
      of several key figures in history. Historical sources recounting strange voices
      and visions may in fact have been describing manifestations of epileptic seizures
      rather than more supernatural phenomena. Well-documented accounts of such
      experiences exist for three individuals in particular: Socrates, St Paul and Joan
      of Arc. The great philosopher Socrates described a 'daimonion' that would visit
      him throughout his life. This daimonion may have represented recurrent simple
      partial seizures, while the peculiar periods of motionlessness for which Socrates
      was well known may have been the result of co-existing complex partial seizures.
      St Paul's religious conversion on the Road to Damascus may have followed a
      temporal lobe seizure which would account for the lights, voices, blindness and
      even the religious ecstasy he described. Finally, Joan of Arc gave a detailed
      narrative on the voices she heard from childhood during her Trial of
      Condemnation. Her auditory hallucinations appear to follow sudden acoustic
      stimuli in a way reminiscent of idiopathic partial epilepsy with auditory
      features. By analysing passages from historical texts, it is possible to argue
      that Socrates, St Paul and Joan of Arc each had epilepsy. 

PMID- 24585827
TI  - Arnault Tzanck (1886-1954), founder of the first blood centre worldwide.
AB  - Arnault Tzanck was at the origins of French transfusion and the founder of the
      first blood centre worldwide. This article retraces his career and personal
      itinerary and that path which led him to give his build the country's first
      organized and modern blood transfusion structure. 

PMID- 24585828
TI  - The history and illustration of anatomy in the Middle Ages.
AB  - This article reviews the influence of key figures on the pictorial representation
      of anatomy and the evolution of anatomical illustration during the Middle Ages
      until the time of the Renaissance, based on medical history books, journals and
      ancient medical books. During the early period in the Middle Ages, most
      illustrations were traditional drawings of emblematic nature, oftentimes
      unrealistic, not only because the precise knowledge of anatomy was lacking but
      also because the objective was to elucidate certain principles for teaching
      purposes. Five figure-series that came down to us through ancient manuscripts and
      textbooks represent the best examples of such traditional illustrations. With the
      advent of human dissection in the 13th and 14th centuries, a significant
      transformation in the depiction of anatomy began to project the practice of human
      dissection, as we see in the works of Mondino de Luzzi, Henri de Mondeville and
      Guido de Vigevano. After the invention of book printing in the second half of the
      15th century, the reproduction of books was commonly practised and the woodcut
      made multiplication of pictures easier. Peter of Abano, Hieronymous Brunschwig,
      Johannes de Ketham, Johannes Peyligk, Gregory Reisch, Magnus Hundt, Laurentius
      Phryesen and many more included several anatomical illustrations in their
      treatises that demonstrated the development of anatomical illustration during the
      later Middle Ages. 

PMID- 24585829
TI  - The making of Ludwig Guttmann.
AB  - Ludwig Guttmann was the founder of the National Spinal Injury Centre at Stoke
      Mandeville Hospital, the first successful unit in Europe to treat spinal injury
      patients. He also founded the paraplegic sports movement. This article is based
      on Guttmann's unpublished autobiography and 25 years of personal experience. He
      was born in Germany where he was trained in neurology, neurosurgery,
      rehabilitation and research by Otfrid Foerster. Guttmann fled Germany in 1939.
      German medicine led the World and Guttmann applied his training to the treatment
      of spinal injury patients in the United Kingdom. 

PMID- 24585830
TI  - Thomas Fresh (1803-1861), Inspector of Nuisances, Liverpool's first public health
      officer.
AB  - Thomas Fresh was Liverpool's first public health officer, having been appointed
      Inspector of Nuisances by the Health of Towns Committee on 4 September 1844, more
      than two years before the celebrated appointment of Duncan as Britain's first
      Medical Officer of Health and Newlands as the first Borough Engineer. Even before
      that, Fresh was the officer responsible for environmental health interventions.
      He is often cited as the first environmental health practitioner. Although he
      gained a national reputation for his work, Fresh was undervalued at the time and
      his life and work have been underreported since. He had an eventful personal
      life. He was married three times and widowed twice. In his youth he spent four
      months on remand before being acquitted. He was a talented entrepreneur: he
      created a building society, a model farm and a residential settlement that today
      bears his name. However, he took on financial commitments that were beyond his
      means, resulting in his sudden and premature departure from public life. 

PMID- 24585831
TI  - Victor Horsley (1857-1915) and National Insurance.
AB  - The Liberal government in 1911 was determined to improve the health care of the
      poor and working class in Britain. The Chancellor of the Exchequer, Lloyd George,
      introduced a National Insurance Bill before Parliament without consulting the
      medical profession. The doctors were furious but Horsley, a progressive liberal,
      was firmly in favour of a national health service and vociferously supported the
      bill. This led to a series of acrimonious meetings that did not enhance the
      reputation of the profession and alienated Horsley from his colleagues. 

PMID- 24585832
TI  - Claude Bernard (1813-1878).

PMID- 24585833
TI  - On the money.

PMID- 24585835
TI  - STENOFOLIA recruits TOPLESS to repress ASYMMETRIC LEAVES2 at the leaf margin and
      promote leaf blade outgrowth in Medicago truncatula.
AB  - The Medicago truncatula WUSCHEL-related homeobox (WOX) gene, STENOFOLIA (STF),
      plays a key role in leaf blade outgrowth by promoting cell proliferation at the
      adaxial-abaxial junction. STF functions primarily as a transcriptional repressor,
      but the underlying molecular mechanism is unknown. Here, we report the
      identification of a protein interaction partner and a direct target, shedding
      light on the mechanism of STF function. Two highly conserved motifs in the C
      terminal domain of STF, the WUSCHEL (WUS) box and the STF box, cooperatively
      recruit TOPLESS (Mt-TPL) family corepressors, and this recruitment is required
      for STF function, as deletion of these two domains (STFdel) impaired blade
      outgrowth whereas fusing Mt-TPL to STFdel restored function. The homeodomain
      motif is required for direct repression of ASYMMETRIC LEAVES2 (Mt-AS2), silencing
      of which partially rescues the stf mutant phenotype. STF and LAMINALESS1 (LAM1)
      are functional orthologs. A single amino acid (Asn to Ile) substitution in the
      homeodomain abolished the repression of Mt-AS2 and STF's ability to complement
      the lam1 mutant of Nicotiana sylvestris. Our data together support a model in
      which STF recruits corepressors to transcriptionally repress its targets during
      leaf blade morphogenesis. We propose that recruitment of TPL/TPL-related proteins
      may be a common mechanism in the repressive function of modern/WUS clade WOX
      genes.

PMID- 24585836
TI  - The ubiquitin receptor DA1 regulates seed and organ size by modulating the
      stability of the ubiquitin-specific protease UBP15/SOD2 in Arabidopsis.
AB  - Although the control of organ size is a fundamental question in developmental
      biology, little is known about the genetic and molecular mechanisms that
      determine the final size of seeds in plants. We previously demonstrated that the
      ubiquitin receptor DA1 acts synergistically with the E3 ubiquitin ligases DA2 and
      ENHANCER1 OF DA1 (EOD1)/BIG BROTHER to restrict seed growth in Arabidopsis
      thaliana. Here, we describe UBIQUITIN-SPECIFIC PROTEASE15 (UBP15), encoded by
      SUPPRESSOR2 OF DA1 (SOD2), which acts maternally to regulate seed size by
      promoting cell proliferation in the integuments of ovules and developing seeds.
      The sod2/ubp15 mutants form small seeds, while overexpression of UBP15 increases
      seed size of wild-type plants. Genetic analyses indicate that UBP15 functions
      antagonistically in a common pathway with DA1 to influence seed size, but does so
      independently of DA2 and EOD1. Further results reveal that DA1 physically
      associates with UBP15 in vitro and in vivo and modulates the stability of UBP15.
      Therefore, our findings establish a genetic and molecular framework for the
      regulation of seed size by four ubiquitin-related proteins DA1, DA2, EOD1, and
      UBP15 and suggest that they are promising targets for increasing seed size in
      crops.

PMID- 24585839
TI  - Some who preceded those of us in 2014.

PMID- 24585837
TI  - Lotus japonicus cytokinin receptors work partially redundantly to mediate nodule
      formation.
AB  - Previous analysis of the Lotus histidine kinase1 (Lhk1) cytokinin receptor gene
      has shown that it is required and also sufficient for nodule formation in Lotus
      japonicus. The L. japonicus mutant carrying the loss-of-function lhk1-1 allele is
      hyperinfected by its symbiotic partner, Mesorhizobium loti, in the initial
      absence of nodule organogenesis. At a later time point following bacterial
      infection, lhk1-1 develops a limited number of nodules, suggesting the presence
      of an Lhk1-independent mechanism. We have tested a hypothesis that other
      cytokinin receptors function in at least a partially redundant manner with LHK1
      to mediate nodule organogenesis in L. japonicus. We show here that L. japonicus
      contains a small family of four cytokinin receptor genes, which all respond to M.
      loti infection. We show that within the root cortex, LHK1 performs an essential
      role but also works partially redundantly with LHK1A and LHK3 to mediate cell
      divisions for nodule primordium formation. The LHK1 receptor is also presumed to
      partake in mediating a feedback mechanism that negatively regulates bacterial
      infections at the root epidermis. Interestingly, the Arabidopsis thaliana AHK4
      receptor gene can functionally replace Lhk1 in mediating nodule organogenesis,
      indicating that the ability to perform this developmental process is not
      determined by unique, legume-specific properties of LHK1.

PMID- 24585838
TI  - RAP, the sole octotricopeptide repeat protein in Arabidopsis, is required for
      chloroplast 16S rRNA maturation.
AB  - The biogenesis and activity of chloroplasts in both vascular plants and algae
      depends on an intracellular network of nucleus-encoded, trans-acting factors that
      control almost all aspects of organellar gene expression. Most of these
      regulatory factors belong to the helical repeat protein superfamily, which
      includes tetratricopeptide repeat, pentatricopeptide repeat, and the recently
      identified octotricopeptide repeat (OPR) proteins. Whereas green algae express
      many different OPR proteins, only a single orthologous OPR protein is encoded in
      the genomes of most land plants. Here, we report the characterization of the only
      OPR protein in Arabidopsis thaliana, RAP, which has previously been implicated in
      plant pathogen defense. Loss of RAP led to a severe defect in processing of
      chloroplast 16S rRNA resulting in impaired chloroplast translation and
      photosynthesis. In vitro RNA binding and RNase protection assays revealed that
      RAP has an intrinsic and specific RNA binding capacity, and the RAP binding site
      was mapped to the 5' region of the 16S rRNA precursor. Nucleoid localization of
      RAP was shown by transient green fluorescent protein import assays, implicating
      the nucleoid as the site of chloroplast rRNA processing. Taken together, our data
      indicate that the single OPR protein in Arabidopsis is important for a basic
      process of chloroplast biogenesis.

PMID- 24585840
TI  - Arthur Conan Doyle (1859-1930): Physician during the typhoid epidemic in the
      Anglo-Boer War (1899-1902).
AB  - When the Anglo-Boer War broke out in October 1899, Arthur Conan Doyle, a retired
      ophthalmologist, was already famous as the creator of Sherlock Holmes. Motivated
      by patriotism and adventure, Doyle joined the medical staff of a private field
      hospital endowed by philanthropist John Langman (1846-1928). Langman Hospital
      opened in Bloemfontein, South Africa, at the height of that city's typhoid fever
      epidemic which raged from April to June 1900. There were nearly 5000 cases of
      typhoid and 1000 deaths but official statistics do not truly reflect the
      magnitude of the suffering. Doyle argued that the British Army had made a major
      mistake by not making antityphoid inoculation compulsory. Because of the new
      vaccine's side effects, 95% of the soldiers refused immunization. Despite his
      strong opinions, Doyle failed to press the issue of compulsory inoculation when
      he testified before two Royal Commissions investigating the medical and military
      management of the war in South Africa. One can only imagine how the army might
      have benefited from the new idea of prophylactic vaccination in preventive
      medicine if Doyle had not let these opportunities slip away. As a consequence,
      antityphoid inoculation was still voluntary when Great Britain entered World War
      I in August 1914. 

PMID- 24585841
TI  - Benjamin Waterhouse (1754-1846) and the riddle of Amos Babcock.
AB  - The late Dr Henry R Viets (1890-1969) suggested in 1940 that the author of A
      Journal of a Young Man of Massachusetts was Amos G Babcock. He also showed that
      Benjamin Waterhouse edited the manuscript. A similar journal, The Prisoner's
      Memoirs of Dartmoor Prison by Charles Andrews, is also described and contrasted.
      The career of Professor Waterhouse is narrated in relation to the medical
      politics at that time in New England: a possible explanation for Babcock's
      anonymous authorship is given. 

PMID- 24585842
TI  - Dr Adolf Lukas Vischer (1884-1974) and 'barbed-wire disease'.
AB  - The Swiss physician Adolf Lukas Vischer described a psychiatric syndrome among
      prisoners of war, the 'barbed-wire disease' that follows a long-term
      incarceration and which involved boredom, confusion, clouding of consciousness
      and amnesia. Vischer first identified this as an important clinical issue. Later
      in life, he became one of the first geriatricians and gerontologists. 

PMID- 24585843
TI  - Geoffrey Layton Slack OBE (Mil), CBE, TD, BDS DDS, FDSRCS, FDS Glas, FFDRCSI, Dip
      Bact (1912-1991).
AB  - It is with some pride that the author worked in Geoffrey Slack's department from
      1963 to 1967 and even retained a working relationship with him after that time.
      Slack was Professor of Dental Surgery (1959-1976) and later Professor of
      Community Dental Health (1976-1977) at The London Hospital Medical College,
      within the University of London. The change in titles came about as a result of
      recognition of his contribution to developments in public health and community
      dental care and services, for many of which he was directly responsible. He was
      Dental Dean from 1965 until 1969. Upon retirement in 1977 he became Emeritus
      Professor. In addition, he was Dean of the Faculty of Dental Surgery at the Royal
      College of Surgeons of England from 1974 to 1977. 

PMID- 24585844
TI  - Hecamede: Homeric nurse of the battle-wounded in the Trojan War.
AB  - The Homeric epics present the 10-year lasting Trojan War, offering the
      description of battle wounds and medical care of injuries. Hecamede is referred
      by the Homer as a battlefield nurse who had knowledge of the treatment of
      bleeding battle wounds. 

PMID- 24585845
TI  - Joseph Hersey Pratt (1872-1956): An early proponent of cognitive-behavioural
      therapy in America.
AB  - The treatment of mild psychoneuroses in America began shifting in the 1950s from
      Freudian psychoanalysis to various forms of psychotherapy that do not delve into
      patient's subconscious. Some of the new approaches were termed cognitive,
      behavioural or cognitive behavioural therapy and in America were practised
      notably by Joseph Wolpe, Albert Ellis and Aaron T Beck. Modern psychiatric
      literature makes little mention of two prior innovators in this area - the French
      neurologist Jules Dejerine and his Boston disciple Joseph H Pratt. In the early
      1900s, Dejerine treated patients at La Salpetriere in Paris using techniques
      adopted subsequently by Pratt during the 1930s and employed by the trio some
      decades later. This paper revisits the early history of psychotherapy in America
      and includes a brief summary of Pratt's medical career. 

PMID- 24585846
TI  - Professor David Poswillo CBE (1927-2003): Skilled oral and maxillofacial surgeon,
      influential scientist, teacher and adviser.
AB  - David Poswillo trained at Otago University Dental School, Dunedin, New Zealand
      (BDS) and the Royal College of Surgeons of England (FDSRCS). His great interest
      became the genesis and repair of cleft lip and palate and, in addition to
      clinical work, he undertook an experimental study of the embryology of cleft
      palate in pregnant rats exposed to three teratogenic agents. The microscopic work
      was carried out in his garden shed in Christchurch. His groundbreaking work on
      amniotic puncture at a critical period came to international notice and he was
      given the first Chair in Teratology of the Royal College of Surgeons. In
      experimental studies he showed that thalidomide induced focal haemorrhage in the
      developing embryo. Poswillo was also Consultant Oral Surgeon at Queen Victoria
      Hospital, East Grinstead and his skills as surgeon and teacher attracted numerous
      trainee surgeons. He was Professor of Oral Surgery in Adelaide and then in
      London. Poswillo was Chairman of two advisory committees whose lucid reports on
      anaesthesia, sedation and resuscitation in dentistry (Poswillo Report) and on
      tobacco and health were far-reaching and influential. David Poswillo had immense
      energy and enthusiasm and is remembered by many for his personal interest and
      stimulating guidance. 

PMID- 24585847
TI  - W Somerset Maugham (1874-1965) and St Thomas's Hospital: Medical School and the
      making of a writer.
AB  - William Somerset Maugham was one of the most successful and prolific authors of
      the twentieth century. He excelled in several genres, writing novels, plays,
      short stories, travel-books, memoir and criticism. His prose style was simple,
      witty; his world view weary and cynical. His childhood was marred by bereavement,
      losing both parents before the age of ten years. He spent a lonely adolescence
      under the guardianship of his uncle, an emotionally distant clergyman. He
      enrolled as a medical student at St Thomas's Hospital mainly to escape from his
      uncle and also to live in London. From his teens his sole ambition was to be a
      writer: medicine did not interest him. Despite his lack of vocation, his five
      years at medical school proved to be the key experience in his artistic
      development. He observed and learned about people; he saw poverty, squalor and
      death. His experience as an Obstetric Clerk in the slums of London inspired his
      first novel, Liza of Lambeth. He qualified but never practised. In old age he
      wrote 'I learned pretty well everything I know about human nature in the 5 years
      I spent at St Thomas's Hospital'. The example of Maugham suggests that medical
      education may have value other than the training of doctors-to-be. 

PMID- 24585848
TI  - John Erichsen's Tonsillectomy Scissors.

PMID- 24585851
TI  - What is it about boys?

PMID- 24585852
TI  - Cohort profile: Wisconsin longitudinal study (WLS).
AB  - The Wisconsin Longitudinal Study (WLS) is a longitudinal study of men and women
      who graduated from Wisconsin high schools in 1957 and one of their randomly
      selected siblings. Wisconsin is located in the upper midwest of the United States
      and had a population of approximately 14 000 000 in 1957, making it the 14th most
      populous state at that time. Data spanning almost 60 years allow researchers to
      link family background, adolescent characteristics, educational experiences,
      employment experiences, income, wealth, family formation and social and religious
      engagement to midlife and late-life physical health, mental health, psychological
      well-being, cognition, end of life planning and mortality. The WLS is one of the
      few longitudinal data sets that include an administrative measure of cognition
      from childhood. Further, recently collected saliva samples allow researchers to
      explore the inter-relationships among genes, behaviours and environment,
      including genetic determinants of behaviours (e.g. educational attainment); the
      interactions between genes and environment; and how these interactions predict
      behaviours. Most panel members were born in 1939, and the sample is broadly
      representative of White, non-Hispanic American men and women who have completed
      at least a high school education. Siblings cover several adjoining cohorts: they
      were born primarily between 1930 and 1948. At each interview, about two-thirds of
      the sample lived in Wisconsin, and about one-third lived elsewhere in the United
      States or abroad. The data, along with documentation, are publicly accessible and
      can be accessed at http://www.ssc.wisc.edu/wlsresearch/. Requests for protected
      data or assistance should be sent to wls@ssc.wisc.edu. 

PMID- 24585854
TI  - An experiment in Beer-tasting.
AB  - An experiment in beer tasting among 18 first year pre-clinical students showed
      that only two appeared to be able to discriminate light from bitter ale
      correctly. As a whole the group did worse than would be expected by guessing at
      random on each tasting trial. Some psychological biases, one possibly as a result
      of the design, are indicated by the results and a possible remedy suggested. The
      danger of acceptance of 'views' in clinical medicine without confirmatory
      experimental evidence was brought out by the students own failure to confirm a
      hypothesis (or 'view') that they believed before hand to be beyond question.

PMID- 24585853
TI  - Data resource profile: the Korea National Health and Nutrition Examination Survey
      (KNHANES).
AB  - The Korea National Health and Nutrition Examination Survey (KNHANES) is a
      national surveillance system that has been assessing the health and nutritional
      status of Koreans since 1998. Based on the National Health Promotion Act, the
      surveys have been conducted by the Korea Centers for Disease Control and
      Prevention (KCDC). This nationally representative cross-sectional survey includes
      approximately 10 000 individuals each year as a survey sample and collects
      information on socioeconomic status, health-related behaviours, quality of life,
      healthcare utilization, anthropometric measures, biochemical and clinical
      profiles for non-communicable diseases and dietary intakes with three component
      surveys: health interview, health examination and nutrition survey. The health
      interview and health examination are conducted by trained staff members,
      including physicians, medical technicians and health interviewers, at a mobile
      examination centre, and dieticians' visits to the homes of the study participants
      are followed up. KNHANES provides statistics for health-related policies in
      Korea, which also serve as the research infrastructure for studies on risk
      factors and diseases by supporting over 500 publications. KCDC has also supported
      researchers in Korea by providing annual workshops for data users. KCDC has
      published the Korea Health Statistics each year, and microdata are publicly
      available through the KNHANES website (http://knhanes.cdc.go.kr). 

PMID- 24585855
TI  - The Ikale collaboration: randomized trials of beer recognition.

PMID- 24585856
TI  - Liver enzymes and risk of all-cause mortality in general populations: a
      systematic review and meta-analysis.
AB  - BACKGROUND: Gamma glutamyltransferase (GGT), alanine aminotransferase (ALT),
      aspartate aminotransferase (AST) and alkaline phosphatase (ALP), commonly used as
      markers of liver dysfunction, have been implicated with risk of all-cause
      mortality. The prospective evidence on the associations in general populations
      has not been reliably quantified. METHODS: We conducted a systematic review and
      meta-analysis of published prospective cohort studies evaluating the associations
      of baseline levels of these enzymes with all-cause mortality in general
      populations. Relevant studies were identified in a literature search of MEDLINE,
      EMBASE and Web of Science up to March 2013. Authors of unpublished studies
      provided data on request. RESULTS: Nineteen unique cohort studies with aggregate
      data on over 9.24 million participants and 242 953 all-cause mortality outcomes
      were included. In a comparison of extreme thirds of baseline GGT and ALP levels,
      relative risks (RRs) (95% confidence intervals) for all-cause mortality were 1.60
      (1.42-1.80) and 1.38 (1.17-1.63), respectively. The corresponding RRs for ALT
      were 0.82 (0.78-0.86) and 1.43 (1.08-1.90) in North American and Asian
      populations, respectively. There was no strong evidence of an association of AST
      with all-cause mortality: RR 1.23 (0.80-1.88). The pooled RRs per 5 U/l increment
      in GGT and ALP levels were 1.07 (1.04-1.10) and 1.03 (1.01-1.06), respectively.
      CONCLUSIONS: Available data indicate positive independent associations of
      baseline levels of GGT and ALP with all-cause mortality, consistent with linear
      dose-response relationships. There were geographical variations in the
      association of ALT with all-cause mortality which require further investigation.
      The potential incremental prognostic values of GGT and ALP in mortality risk
      assessment need evaluation.

PMID- 24585857
TI  - Development of an instrument to evaluate intrapartum care quality in Senegal:
      evaluation quality care.
AB  - OBJECTIVE: To evaluate the reliability of direct observation for measuring
      intrapartum care and compare this method with clinical audits using objective
      criteria based on patients' medical charts. DESIGN: Cross-sectional study, data
      collected by two independent evaluators. SETTING: Hospital in Dakar, Senegal.
      PARTICIPANTS: Thirty consecutive intrapartum care episodes provided by midwives
      and the corresponding medical charts. Outcome Measure The presence or absence of
      each of twelve criteria selected on the basis of national and international norms
      for monitoring of labour and delivery (six criteria) and the immediate postpartum
      period (six criteria). RESULTS: For direct observation, the labour and delivery
      mean quality scores ranged from 5.34 to 5.77. In contrast, for the chart-based
      method, the scores ranged from 0.32 to 0.45. For postpartum care evaluated only
      with direct observation, the scores were also high (5.21-5.65). For direct
      observation, inter-evaluator agreement was high: kappa coefficients varied from
      0.78 to 0.93 depending on the criterion (total score ICC = 0.74). For the chart
      based method, inter-evaluator agreement was also high: 0.66 to 1 (total score ICC
      = 0.72). Comparison of the two methods showed strong differences by items and
      subscores. CONCLUSION: Using direct observation, the quality of obstetric care
      was high for both the monitoring of labour and delivery and postpartum care. Both
      measurement instruments showed high reliability. The chart-based method
      underestimated the quality of care because of poor medical record documentation.
      Medical-record-based measurement may not be appropriate for the evaluation of the
      quality of obstetric care in Senegal and other low-income settings.

PMID- 24585858
TI  - The "other" COPD.

PMID- 24585859
TI  - Measuring and quantifying acute exacerbations of COPD: pitfalls and
      practicalities.

PMID- 24585860
TI  - Monitoring disease progression in COPD patients: one step beyond!

PMID- 24585861
TI  - Systemic steroids in severe forms of COPD exacerbations: a question of balance?

PMID- 24585862
TI  - Protocadherin-1: Epithelial barrier dysfunction in asthma and eczema.

PMID- 24585863
TI  - Increased daily activity in cystic fibrosis: time to break out the prescription
      pad?

PMID- 24585864
TI  - Paediatric tuberculosis in Europe: lessons from Denmark and inclusive strategies
      to consider.

PMID- 24585865
TI  - Inflammation in pulmonary arterial hypertension: is it time to quell the fire?

PMID- 24585867
TI  - Asthma and pulmonary embolism: bringing airways and vessels closer together.

PMID- 24585868
TI  - The tuberculosis time bomb: taking control of the TB threat in Europe.

PMID- 24585869
TI  - From the museum: the art of thinking.

PMID- 24585870
TI  - From the museum: the art of thinking. Part one: thinking.

PMID- 24585871
TI  - Prediction of outcome after PEA in chronic thromboembolic pulmonary hypertension
      using indexed pulmonary artery diameter.

PMID- 24585872
TI  - Patient selection before endobronchial valve treatment.

PMID- 24585866
TI  - Prediction of chronic lung allograft dysfunction: a systems medicine challenge.

PMID- 24585873
TI  - Infant lung function and wheeze in later childhood in the Southampton Women's
      Survey.

PMID- 24585874
TI  - Infant lung function and wheeze in later childhood in the Southampton Women's
      Survey.

PMID- 24585875
TI  - Bronchoalveolar lavage cytology resembles sarcoidosis in a subgroup of
      granulomatous CVID.

PMID- 24585876
TI  - Bronchoalveolar lavage cytology resembles sarcoidosis in a subgroup of
      granulomatous CVID.

PMID- 24585878
TI  - Modification of T cell responses by stem cell mobilization requires direct
      signaling of the T cell by G-CSF and IL-10.
AB  - The majority of allogeneic stem cell transplants are currently undertaken using G
      CSF mobilized peripheral blood stem cells. G-CSF has diverse biological effects
      on a broad range of cells and IL-10 is a key regulator of many of these effects.
      Using mixed radiation chimeras in which the hematopoietic or nonhematopoietic
      compartments were wild-type, IL-10(-/-), G-CSFR(-/-), or combinations thereof we
      demonstrated that the attenuation of alloreactive T cell responses after G-CSF
      mobilization required direct signaling of the T cell by both G-CSF and IL-10. IL
      10 was generated principally by radio-resistant tissue, and was not required to
      be produced by T cells. G-CSF mobilization significantly modulated the
      transcription profile of CD4(+)CD25(+) regulatory T cells, promoted their
      expansion in the donor and recipient and their depletion significantly increased
      graft-versus-host disease (GVHD). In contrast, stem cell mobilization with the
      CXCR4 antagonist AMD3100 did not alter the donor T cell's ability to induce acute
      GVHD. These studies provide an explanation for the effects of G-CSF on T cell
      function and demonstrate that IL-10 is required to license regulatory function
      but T cell production of IL-10 is not itself required for the attenuation GVHD.
      Although administration of CXCR4 antagonists is an efficient means of stem cell
      mobilization, this fails to evoke the immunomodulatory effects seen during G-CSF
      mobilization. These data provide a compelling rationale for considering the
      immunological benefits of G-CSF in selecting mobilization protocols for
      allogeneic stem cell transplantation. 

PMID- 24585879
TI  - The RhoA guanine nucleotide exchange factor, LARG, mediates ICAM-1-dependent
      mechanotransduction in endothelial cells to stimulate transendothelial migration.
AB  - RhoA-mediated cytoskeletal rearrangements in endothelial cells (ECs) play an
      active role in leukocyte transendothelial cell migration (TEM), a normal
      physiological process in which leukocytes cross the endothelium to enter the
      underlying tissue. Although much has been learned about RhoA signaling pathways
      downstream from ICAM-1 in ECs, little is known about the consequences of the
      tractional forces that leukocytes generate on ECs as they migrate over the
      surface before TEM. We have found that after applying mechanical forces to ICAM-1
      clusters, there is an increase in cellular stiffening and enhanced RhoA signaling
      compared with ICAM-1 clustering alone. We have identified that leukemia
      associated Rho guanine nucleotide exchange factor (LARG), also known as Rho GEF
      12 (ARHGEF12) acts downstream of clustered ICAM-1 to increase RhoA activity, and
      that this pathway is further enhanced by mechanical force on ICAM-1. Depletion of
      LARG decreases leukocyte crawling and inhibits TEM. To our knowledge, this is the
      first report of endothelial LARG regulating leukocyte behavior and EC stiffening
      in response to tractional forces generated by leukocytes. 

PMID- 24585880
TI  - Nerve growth factor downregulates inflammatory response in human monocytes
      through TrkA.
AB  - Nerve growth factor (NGF) levels are highly increased in inflamed tissues, but
      their role is unclear. We show that NGF is part of a regulatory loop in
      monocytes: inflammatory stimuli, while activating a proinflammatory response
      through TLRs, upregulate the expression of the NGF receptor TrkA. In turn, NGF,
      by binding to TrkA, interferes with TLR responses. In TLR-activated monocytes,
      NGF reduces inflammatory cytokine production (IL-1beta, TNF-alpha, IL-6, and IL
      8) while inducing the release of anti-inflammatory mediators (IL-10 and IL-1
      receptor antagonist). NGF binding to TrkA affects TLR signaling, favoring
      pathways that mediate inhibition of inflammatory responses: it increases Akt
      phosphorylation, inhibits glycogen synthase kinase 3 activity, reduces IkappaB
      phosphorylation and p65 NF-kappaB translocation, and increases nuclear p50 NF
      kappaB binding activity. Use of TrkA inhibitors in TLR-activated monocytes
      abolishes the effects of NGF on the activation of anti-inflammatory signaling
      pathways, thus increasing NF-kappaB pathway activation and inflammatory cytokine
      production while reducing IL-10 production. PBMC and mononuclear cells obtained
      from the synovial fluid of patients with juvenile idiopathic arthritis show
      marked downregulation of TrkA expression. In ex vivo experiments, the addition of
      NGF to LPS-activated juvenile idiopathic arthritis to both mononuclear cells from
      synovial fluid and PBMC fails to reduce the production of IL-6 that, in contrast,
      is observed in healthy donors. This suggests that defective TrkA expression may
      facilitate proinflammatory mechanisms, contributing to chronic tissue
      inflammation and damage. In conclusion, this study identifies a novel regulatory
      mechanism of inflammatory responses through NGF and its receptor TrkA, for which
      abnormality may have pathogenic implications for chronic inflammatory diseases. 

PMID- 24585881
TI  - The path to triacylglyceride obesity in the sta6 strain of Chlamydomonas
      reinhardtii.
AB  - When the sta6 (starch-null) strain of the green microalga Chlamydomonas
      reinhardtii is nitrogen starved in acetate and then "boosted" after 2 days with
      additional acetate, the cells become "obese" after 8 days, with triacylglyceride
      (TAG)-filled lipid bodies filling their cytoplasm and chloroplasts. To assess the
      transcriptional correlates of this response, the sta6 strain and the starch
      forming cw15 strain were subjected to RNA-Seq analysis during the 2 days prior
      and 2 days after the boost, and the data were compared with published reports
      using other strains and growth conditions. During the 2 h after the boost, ~425
      genes are upregulated >=2-fold and ~875 genes are downregulated >=2-fold in each
      strain. Expression of a small subset of "sensitive" genes, encoding enzymes
      involved in the glyoxylate and Calvin-Benson cycles, gluconeogenesis, and the
      pentose phosphate pathway, is responsive to culture conditions and genetic
      background as well as to boosting. Four genes-encoding a diacylglycerol
      acyltransferase (DGTT2), a glycerol-3-P dehydrogenase (GPD3), and two candidate
      lipases (Cre03.g155250 and Cre17.g735600)-are selectively upregulated in the sta6
      strain. Although the bulk rate of acetate depletion from the medium is not boost
      enhanced, three candidate acetate permease-encoding genes in the GPR1/FUN34/YaaH
      superfamily are boost upregulated, and 13 of the "sensitive" genes are strongly
      responsive to the cell's acetate status. A cohort of 64 autophagy-related genes
      is downregulated by the boost. Our results indicate that the boost serves both to
      avert an autophagy program and to prolong the operation of key pathways that
      shuttle carbon from acetate into storage lipid, the combined outcome being
      enhanced TAG accumulation, notably in the sta6 strain. 

PMID- 24585882
TI  - Pbx proteins in Cryptococcus neoformans cell wall remodeling and capsule
      assembly.
AB  - The cryptococcal capsule is a critical virulence factor of an important pathogen,
      but little is known about how it is associated with the cell or released into the
      environment. Two mutants lacking PBX1 and PBX2 were found to shed reduced amounts
      of the capsule polysaccharide glucuronoxylomannan (GXM). Nuclear magnetic
      resonance, composition, and physical analyses showed that the shed material was
      of normal mass but was slightly enriched in xylose. In contrast to previous
      reports, this material contained no glucose. Notably, the capsule fibers of
      pbxDelta mutant cells grown under capsule-inducing conditions were present at a
      lower than usual density and were loosely attached to the cell wall. Mutant cell
      walls were also defective, as indicated by phenotypes including abnormal cell
      morphology, reduced mating filamentation, and altered cell integrity. All
      observed phenotypes were shared between the two mutants and exacerbated in a
      double mutant. Consistent with a role in surface glycan synthesis, the Pbx
      proteins localized to detergent-resistant membrane domains. These results,
      together with the sequence motifs in the Pbx proteins, suggest that Pbx1 and Pbx2
      are redundant proteins that act in remodeling the cell wall to maintain normal
      cell morphology and precursor availability for other glycan synthetic processes.
      Their absence results in aberrant cell wall growth and metabolic imbalance, which
      together impact cell wall and capsule synthesis, cell morphology, and capsule
      association. The surface changes also lead to increased engulfment by host
      phagocytes, consistent with the lack of virulence of pbx mutants in animal
      models. 

PMID- 24585884
TI  - Sudden unexplained death in infants and children: the role of undiagnosed
      inherited cardiac conditions.
AB  - Sudden unexplained death in childhood is a traumatic event for both the immediate
      family and medical professionals. This is termed sudden unexplained or arrhythmic
      death syndrome (SUDS/SADS) for children over 1 year of age while sudden
      unexplained death in infancy or sudden infant death syndrome (SUDI/SIDS) refers
      to unexplained deaths in the first year of life. There is increasing evidence for
      the role of undiagnosed inherited cardiac conditions, particularly
      channelopathies, as the cause of these deaths. This has far-reaching implications
      for the family regarding the potential risk to other family members and future
      pregnancies, providing a challenge not only in the counselling but also in the
      structured assessment and management of immediate relatives. This review will
      discuss the cardiac risk involved in sudden unexplained deaths of infants and
      children, the role of molecular autopsy, family cardiological screening, current
      management strategies, and future directions in this area. 

PMID- 24585885
TI  - The rise of progressive dwindling.

PMID- 24585883
TI  - Inhibition and structure of Toxoplasma gondii purine nucleoside phosphorylase.
AB  - The intracellular pathogen Toxoplasma gondii is a purine auxotroph that relies on
      purine salvage for proliferation. We have optimized T. gondii purine nucleoside
      phosphorylase (TgPNP) stability and crystallized TgPNP with phosphate and
      immucillin-H, a transition-state analogue that has high affinity for the enzyme.
      Immucillin-H bound to TgPNP with a dissociation constant of 370 pM, the highest
      affinity of 11 immucillins selected to probe the catalytic site. The specificity
      for transition-state analogues indicated an early dissociative transition state
      for TgPNP. Compared to Plasmodium falciparum PNP, large substituents surrounding
      the 5'-hydroxyl group of inhibitors demonstrate reduced capacity for TgPNP
      inhibition. Catalytic discrimination against large 5' groups is consistent with
      the inability of TgPNP to catalyze the phosphorolysis of 5'-methylthioinosine to
      hypoxanthine. In contrast to mammalian PNP, the 2'-hydroxyl group is crucial for
      inhibitor binding in the catalytic site of TgPNP. This first crystal structure of
      TgPNP describes the basis for discrimination against 5'-methylthioinosine and
      similarly 5'-hydroxy-substituted immucillins; structural differences reflect the
      unique adaptations of purine salvage pathways of Apicomplexa. 

PMID- 24585886
TI  - The medical miracles delusion.

PMID- 24585887
TI  - Periodontal disease and systemic disease.

PMID- 24585888
TI  - Nasarwanji Hormusji Choksy (1861-1939): a pioneer of controlled clinical trials.

PMID- 24585892
TI  - Validity of a simple Internet-based outcome-prediction tool in patients with
      total hip replacement: a pilot study.
AB  - We developed a user-friendly Internet-based tool for patients undergoing total
      hip replacement (THR) due to osteoarthritis to predict their pain and function
      after surgery. In the first step, the key questions were identified by
      statistical modelling in a data set of 375 patients undergoing THR. Based on
      multiple regression, we identified the two most predictive WOMAC questions for
      pain and the three most predictive WOMAC questions for functional outcome, while
      controlling for comorbidity, body mass index, age, gender and specific
      comorbidities relevant to the outcome. In the second step, a pilot study was
      performed to validate the resulting tool against the full WOMAC questionnaire
      among 108 patients undergoing THR. The mean difference between observed (WOMAC)
      and model-predicted value was -1.1 points (95% confidence interval, CI -3.8, 1.5)
      for pain and -2.5 points (95% CI -5.3, 0.3) for function. The model-predicted
      value was within 20% of the observed value in 48% of cases for pain and in 57% of
      cases for function. The tool demonstrated moderate validity, but performed weakly
      for patients with extreme levels of pain and extreme functional limitations at 3
      months post surgery. This may have been partly due to early complications after
      surgery. However, the outcome-prediction tool may be useful in helping patients
      to become better informed about the realistic outcome of their THR.

PMID- 24585893
TI  - Low proportions of CD28- CD8+ T cells expressing CD57 can be reversed by early
      ART initiation and predict mortality in treated HIV infection.
AB  - BACKGROUND: Unlike cytomegalovirus (CMV) infection and aging, human
      immunodeficiency virus (HIV) decreases the proportion of CD28(-)CD8(+) T cells
      expressing CD57. Whether this abnormality predicts mortality in treated HIV
      infection and can be reversed by early antiretroviral therapy (ART) remains
      unknown. METHODS: We sampled recently HIV-infected individuals (<6 months) and
      HIV-uninfected controls and compared longitudinal changes in the proportion of
      CD28(-)CD8(+) T cells expressing CD57 between those who initiated ART early (<6
      months) vs later (>=2 years). We also assessed the relationship between this
      phenotype and mortality in a nested case-control study of ART-suppressed
      chronically infected individuals. RESULTS: Compared to HIV-uninfected controls (n
      = 15), individuals who were recently infected with HIV had lower proportions of
      CD28(-)CD8(+) T cells expressing CD57 (P < .001), and these proportions increased
      during ART. The early ART group (n = 33) achieved normal levels, whereas the
      later ART group (n = 30) continued to have lower levels than HIV-uninfected
      controls (P = .02). Among 141 ART-suppressed participants in the SOCA study,
      those in the lowest quartile of CD28(-)CD8(+) T cells expressing CD57 had 5-fold
      higher odds of mortality than those in the highest quartile (95% CI, 1.6-15.9, P
      = .007). CONCLUSIONS: Abnormally low proportions of CD28(-)CD8(+) T cells
      expressing CD57 predict increased mortality during treated HIV infection and may
      be reversed with early ART initiation.

PMID- 24585895
TI  - Periportal CD4+ cell infiltration increases in HIV/hepatitis C virus-coinfected
      patients commencing ART, whereas CD8+ cells clear from the liver.
AB  - Coinfection with human immunodeficiency virus (HIV) and hepatitis C virus (HCV)
      is common in Asia, but the effects of antiretroviral therapy (ART) are unclear.
      Histopathological changes in the liver are described in a prospective study of
      HCV-seropositive HIV-infected patients at Cipto Mangunkusomo Hospital (Jakarta,
      Indonesia). Liver biopsy specimens were collected at baseline (n = 48) and 48
      weeks (n = 34). Ishak scores showed mild but detectable inflammation and/or
      fibrosis. Levels of portal inflammation declined during ART (P = .03), whereas
      fibrosis remained (P = .11). Portal infiltration of CD4(+) cells increased during
      ART (P < .0001), whereas infiltration of CD8(+) cells subsided. Numbers of CD4(+)
      cells in the liver at baseline correlated with circulating CD4(+) T-cell counts
      (P = .03-.05). Numbers of liver-infiltrating CD4(+) and CD8(+) cells at baseline
      were not associates with subsequent experience of an immune restoration disease,
      which is defined by a rise in alanine transaminase levels during ART.

PMID- 24585894
TI  - DNA vaccine initiates replication of live attenuated chikungunya virus in vitro
      and elicits protective immune response in mice.
AB  - BACKGROUND: Chikungunya virus (CHIKV) causes outbreaks of chikungunya fever
      worldwide and represents an emerging pandemic threat. Vaccine development against
      CHIKV has proved challenging. Currently there is no approved vaccine or specific
      therapy for the disease. METHODS: To develop novel experimental CHIKV vaccine, we
      used novel immunization DNA (iDNA) infectious clone technology, which combines
      the advantages of DNA and live attenuated vaccines. Here we describe an iDNA
      vaccine composed of plasmid DNA that encode the full-length infectious genome of
      live attenuated CHIKV clone 181/25 downstream from a eukaryotic promoter. The
      iDNA approach was designed to initiate replication of live vaccine virus from the
      plasmid in vitro and in vivo. RESULTS: Experimental CHIKV iDNA vaccines were
      prepared and evaluated in cultured cells and in mice. Transfection with 10 ng of
      iDNA was sufficient to initiate replication of vaccine virus in vitro.
      Vaccination of BALB/c mice with a single 10 MUg of CHIKV iDNA plasmid resulted in
      seroconversion, elicitation of neutralizing antibodies, and protection from
      experimental challenge with a neurovirulent CHIKV. CONCLUSIONS: Live attenuated
      CHIKV 181/25 vaccine can be delivered in vitro and in vivo by using DNA
      vaccination. The iDNA approach appears to represent a promising vaccination
      strategy for CHIK and other alphaviral diseases.

PMID- 24585898
TI  - Lipopolysaccharide, immune activation, and liver abnormalities in HIV/hepatitis B
      virus (HBV)-coinfected individuals receiving HBV-active combination
      antiretroviral therapy.
AB  - We investigated the relationship between microbial translocation, immune
      activation, and liver disease in human immunodeficiency virus (HIV)/hepatitis B
      virus (HBV) coinfection. Lipopolysaccharide (LPS), soluble CD14, CXCL10, and CCL
      2 levels were elevated in patients with HIV/HBV coinfection. Levels of LPS,
      soluble CD14, and CCL-2 declined following receipt of HBV-active combination
      antiretroviral therapy (cART), but the CXCL10 level remained elevated. No markers
      were associated with liver disease severity on liver biopsy (n = 96), but CXCL10,
      interleukin 6 (IL-6), interleukin 10 (IL-10), tumor necrosis factor alpha, and
      interferon gamma (IFN-gamma) were all associated with elevated liver enzyme
      levels during receipt of HBV-active cART. Stimulation of hepatocyte cell lines in
      vitro with IFN-gamma and LPS induced a profound synergistic increase in the
      production of CXCL10. LPS may contribute to liver disease via stimulating
      persistent production of CXCL10. 

PMID- 24585897
TI  - Inflammatory cytokines drive CD4+ T-cell cycling and impaired responsiveness to
      interleukin 7: implications for immune failure in HIV disease.
AB  - BACKGROUND: Systemic inflammation has been linked to a failure to normalize
      CD4(+) T-cell numbers in treated human immunodeficiency virus (HIV) infection.
      Although inflammatory cytokines such as interleukin 6 (IL-6) are predictors of
      disease progression in treated HIV infection, it is not clear how or whether
      inflammatory mediators contribute to immune restoration failure. METHODS: We
      examined the in vitro effects of IL-6 and interleukin 1beta (IL-1beta) on
      peripheral blood T-cell cycling and CD127 surface expression. RESULTS: The
      proinflammatory cytokine IL-1beta induces cell cycling and turnover of memory
      CD4(+) T cells, and IL-6 can induce low-level cycling of naive T cells. Both IL
      1beta and IL-6 can decrease T-cell surface expression and RNA levels of CD127,
      the interleukin 7 receptor alpha chain (IL-7Ralpha). Preexposure of healthy
      peripheral blood mononuclear cells (PBMCs) to IL-6 or IL-1beta attenuates IL-7
      induced Stat5 phosphorylation and induction of the prosurvival factor Bcl-2 and
      the gut homing integrin alpha4beta7. We found elevated expression of IL-1beta in
      the lymphoid tissues of patients with HIV infection that did not normalize with
      antiretroviral therapy. CONCLUSIONS: Induction of CD4(+) T-cell turnover and
      diminished T-cell responsiveness to IL-7 by IL-1beta and IL-6 exposure may
      contribute to the lack of CD4(+) T-cell reconstitution in treated HIV-infected
      subjects.

PMID- 24585896
TI  - Incomplete reversibility of estimated glomerular filtration rate decline
      following tenofovir disoproxil fumarate exposure.
AB  - BACKGROUND: Tenofovir disoproxil fumarate (TDF) has been linked to renal
      impairment, but the extent to which this impairment is reversible is unclear. We
      aimed to investigate the reversibility of renal decline during TDF therapy.
      METHODS: Cox proportional hazards models assessed factors associated with
      discontinuing TDF in those with an exposure duration of >6 months. In those who
      discontinued TDF therapy, linear piecewise regression models estimated glomerular
      filtration rate (eGFR) slopes before initiation of, during, and after
      discontinuation of TDF therapy. Factors associated with not achieving eGFR
      recovery 6 months after discontinuing TDF were assessed using multivariable
      logistic regression. RESULTS: We observed declines in the eGFR during TDF
      exposure (mean slopes, -15.7 mL/minute/1.73 m(2)/year [95% confidence interval
      {CI}, -20.5 to -10.9] during the first 3 months and -3.1 mL/minute/1.73 m(2)/year
      [95% CI, -4.6 to -1.7] thereafter) and evidence of eGFR increases following
      discontinuation of TDF therapy (mean slopes, 12.5 mL/minute/1.73 m(2)/year [95%
      CI, 8.9-16.1] during the first 3 months and 0.8 mL/minute/1.73 m(2)/year [95% CI,
      .1-1.5] thereafter). Following TDF discontinuation, 38.6% of patients with a
      decline in the eGFR did not experience recovery. A higher eGFR at baseline, a
      lower eGFR after discontinuation of TDF therapy, and more-prolonged exposure to
      TDF were associated with an increased risk of incomplete recovery 6 months after
      discontinuation of TDF therapy. CONCLUSIONS: This study shows that a decline in
      the eGFR during TDF therapy was not fully reversible in one third of patients and
      suggests that prolonged TDF exposure at a low eGFR should be avoided.

PMID- 24585900
TI  - Initial large-dose administration of modified St. Thomas' solution.
AB  - BACKGROUND: We introduced an initial large dose of modified St. Thomas' Hospital
      cardioplegic solution with the aim of providing both myocardial protection as
      well as a smooth intraoperative process. METHODS: In 90 cases of isolated aortic
      valve replacement, we used the modified technique of cardioplegia in 45 (group S)
      and conventional administration of glucose-insulin-potassium solution in 45
      (group G). The patients were selected at random. In group S, we added 4 mEq of
      potassium to the original St. Thomas' Hospital solution and administered 30
      mL.kg(-1) as an initial dose. The temperature was decreased to 2. RESULTS: The
      mean of reperfusion time after declamping in group S was significantly shorter
      (16.7 +/- 6.4 vs. 21.5 +/- 10.0 min; p = 0.007). The average of postoperative
      maximum creatine kinase-MB was significantly lower in group S (25.6 +/- 9.5 vs.
      40.6 +/- 37.2 IU.L(-1); p = 0.014). On multivariate analysis, use of the modified
      cardioplegia and aortic crossclamp time were significantly associated with
      creatine kinase-MB level and reperfusion time after declamping. CONCLUSIONS: This
      modified technique was an acceptable option that provided a bloodless operative
      field and avoided multiple cardioplegic administrations.

PMID- 24585899
TI  - The kynurenine pathway of tryptophan catabolism, CD4+ T-cell recovery, and
      mortality among HIV-infected Ugandans initiating antiretroviral therapy.
AB  - BACKGROUND: Human immunodeficiency virus (HIV) infection-induced indoleamine 2,3
      dioxygenase-1 (IDO) expression in activated monocytes and dendritic cells
      catabolizes tryptophan to kynurenine and other downstream catabolites that
      inhibit T-cell proliferation and interleukin 17 (IL-17) production. The
      prognostic significance of this pathway in treated HIV disease is unknown.
      METHODS: We measured systemic IDO activity (calculated as the ratio of plasma
      levels of kynurenine to tryptophan; hereafter, the "KT ratio") in HIV-infected
      Ugandans before and during antiretroviral therapy (ART)-mediated viral
      suppression and its association with the rate of subsequent CD4(+) T-cell count
      recovery and mortality. RESULTS: Among 435 participants, a higher pre-ART KT
      ratio was associated with a higher plasma virus load (P < .001) and
      lipopolysaccharide level (P = .018), a lower CD4(+) T-cell count (P < .001), and
      female sex (P = .047). Through month 12 of ART-mediated viral suppression, the
      plasma KT ratio decreased by approximately 50% (P < .001). After adjustment for
      pre-ART CD4(+) T-cell count, virus load, age, and sex, a higher month 12 KT ratio
      predicted a slower rate of subsequent CD4(+) T-cell count recovery (P = .001).
      Thirty-nine participants died. After adjustment for pre-ART CD4(+) T-cell count,
      virus load, body mass index, sex, and age, a higher pre-ART and month 6 KT ratio
      predicted increased mortality (P <= .016). CONCLUSIONS: The kynurenine pathway of
      tryptophan catabolism independently predicts poor CD4(+) T-cell count recovery
      and increased mortality among HIV-infected Ugandans initiating ART and may be an
      important target for interventions.

PMID- 24585901
TI  - Aortopulmonary window: a single institution surgical experience.
AB  - BACKGROUND: Aortopulmonary window is a rare cardiac anomaly. We report our
      experience with this rare lesion and highlight the criteria for treating this
      defect without the use of cardiopulmonary bypass. METHODS: From May 2007 to April
      2012, 10 patients, aged 1 to 10 months and weighing 3.4 to 5.5 kg, were operated
      on by a single surgeon using both off-pump and standard techniques. All patients
      underwent preoperative and postoperative echocardiographic assessment, and were
      followed up with clinical examinations and echocardiography. RESULTS: There was
      no operative death and all patients were alive at the last follow-up. No major
      morbidities were noted. Two cases were operated on off-pump and they had shorter
      intensive care unit stays. All patients were in New York Heart Association class
      I on follow-up, with no residual shunt noted in follow-up echocardiograms.
      CONCLUSIONS: The surgical closure of aortopulmonary window carries a low surgical
      risk. Early surgical closure prevents the development of pulmonary vascular
      disease and achieves good immediate and long-term outcomes. Off-pump repair
      techniques, when used judiciously, have a place in the treatment of this defect.

PMID- 24585902
TI  - Ischemic preconditioning reduces apoptosis in open heart surgery.
AB  - BACKGROUND: This study was performed to assess the role of ischemic
      preconditioning on cardiomyocyte apoptosis after open heart surgery, based on
      morphology by transmission electron microscopy, caspase-3 activity, biochemical
      markers, and cardiac performance. METHODS: 12 piglets were divided into 2 equal
      groups: an ischemic preconditioning group and a control group. Ventricular
      muscles were collected to examine apoptotic ultrastructure morphology and caspase
      3 activity. Blood samples from the coronary sinus were obtained for measurement
      of tumor necrosis factor-alpha, malondialdehyde, and cardiac troponin I. Aortic
      blood samples were taken for lactate measurements before and after
      cardiopulmonary bypass. Cardiac performance was measured by echocardiography
      before and after surgery. RESULTS: Cardiomyocyte apoptosis occurred
      postoperatively, as shown by ultrastructure observation. Caspase-3 activity was
      less in the ischemic preconditioning group than the control group (p < 0.05).
      Measurements of specific markers of cardiomyocyte injury also showed lower
      increases in the ischemic preconditioning group, although not significantly
      different. Clinical outcomes showed that ischemic preconditioning was able to
      preserve cardiac performance in terms of ejection fraction, cardiac index, and
      stroke volume index; these were statistically significant, except for lactate
      concentration. CONCLUSIONS: Cardiomyocyte apoptosis occurs after open heart
      surgery. Ischemic preconditioning can reduce cardiomyocyte apoptosis and improve
      cardiac performance. Laboratory findings showed that ischemic preconditioning
      prevents injury of cardiomyocytes and reduces lactate concentration, although not
      statistically significant.

PMID- 24585903
TI  - A selection of cases of direct cannulation in surgery for type A dissection.
AB  - BACKGROUND: We use antegrade cannulation, circulatory arrest, and selective
      antegrade cerebral perfusion in patients with acute aortic dissection. While
      blood is generally supplied via the ascending aorta, this route can be difficult,
      depending on the features of dissection and the form of the true lumen. In such
      cases, we incise the ascending aorta and insert the cannula directly into the
      true lumen of the ascending aorta to secure the blood supply. METHODS: Between
      April 2005 and April 2012, direct true lumen cannulation of the ascending aorta
      was performed in 12 patients; 5 had total arch replacement, and 7 had ascending
      aorta and hemiarch replacement. RESULTS: Total arch replacement involved
      circulatory arrest for 62 +/- 16 min, aortic crossclamping for 174 +/- 13 min,
      cardiopulmonary bypass for 211 +/- 11 min, and a minimal rectal temperature of
      28.4 +/- 1.8. Ascending aorta and hemiarch replacement involved arrest of the
      circulation for 40 +/- 9 min, aortic crossclamping for 111 +/- 29 min,
      cardiopulmonary bypass for 131 +/- 34 min, and a minimal rectal temperature of
      27.8 +/- 0.9. One patient died from cerebral infarction during hospitalization.
      CONCLUSION: In these cases, direct true lumen cannulation of the ascending aorta
      was effective.

PMID- 24585904
TI  - Stroke volume paradox in heart failure: mathematical validation.
AB  - BACKGROUND: In some patients with ischemic cardiomyopathy, despite large
      increases in ventricular size with decreased cardiac output, the paradox of
      preserved stroke volume has been observed. Following surgical ventricular
      restoration, despite marked improvements clinically and in ventricular volumes
      and ejection fraction, a decrease in stroke volume was observed. METHODS: 101
      consecutive patients with postinfarction left ventricular aneurysms were studied
      by 2-dimensional echocardiography and contrast ventriculography at baseline, and
      57 of these patients at 1.7 to 2.2 years (mean 1.95 +/- 0.44 years) after
      surgical ventricular restoration. RESULTS: Surgical ventricular restoration
      resulted in a decrease in end-diastolic volume index of 40.2 mL (95% confidence
      interval: 33.6-46.7) and stroke volume index of 10.0 mL (95% confidence interval:
      6.6-13.5), and an increase in ejection fraction of 6.7% (95% confidence interval:
      5.5-7.9). The stroke volume index had a significant linear relationship with the
      end-diastolic volume index at rest in patients with end-diastolic volume index <
      150 mL (r = 0.64, p < 0.001). In patients with end-diastolic volume index >150
      mL, this linear relationship was not seen. The change in end-diastolic volume
      index and stroke volume index had a significant linear relationship (r = 0.72, p
      < 0.001) that persisted at 1.95 years after surgery. CONCLUSIONS: In ischemic
      cardiomyopathy, stroke volume increases linearly with increases in end-diastolic
      volume up to a certain magnitude of end-diastolic volume, beyond which it
      decreases. Hence, following surgical ventricular restoration, decreases in stroke
      volume are not a reflection of impaired cardiac function.

PMID- 24585905
TI  - Pericardiectomy for treatment of neoplastic constrictive pericarditis.
AB  - OBJECTIVE: To share our results of a case series of 8 patients who underwent
      pericardiectomy for constrictive pericarditis that developed secondary to a known
      neoplastic disease. PATIENTS AND METHODS: The underlying neoplasia was lung
      cancer in 5 (62.5%) patients, malignant pleural mesothelioma in 2 (25%), and
      Hodgkin lymphoma in 1 (12.5%). A diagnosis of constrictive pericarditis was made
      primarily by echocardiography, and right heart catheterization was performed in 6
      (75%) patients. Total pericardiectomy was defined as wide excision of the
      anterior pericardium. Follow-up information was obtained by telephone interview
      and the civil registry database. RESULTS: Time from initial diagnosis of the
      neoplastic disease ranged from 1 to 15 years. Total pericardiectomy was performed
      in 6 (75%) patients. Histopathological examination revealed atypical cells in
      evacuated fluid and pericardial material in 6 patients. Nonspecific inflammation
      and fibrosis were observed in the other 2 cases. Hospital death occurred in 1
      (12.5%) patient. Postoperative low cardiac output syndrome occurred in 7 (87.5%)
      patients. Follow-up ranged from 2.92 to 26.78 months. Mean survival was 14.82 +/-
      4.4 months. CONCLUSION: Pericardial constriction may develop a long time after
      the initial presentation of certain neoplastic diseases, and the prognosis after
      pericardiectomy is poor.

PMID- 24585906
TI  - Atrial natriuretic peptide property on the ischemic myocardium inducing HSP72.
AB  - BACKGROUND: The purpose of this study was to investigate the effectiveness of
      atrial natriuretic peptide on ischemic myocardium through the induction of heat
      shock protein 72. METHODS: 30 isolated rabbit hearts perfused on isolated heart
      apparatus were randomly assigned to receive either warm Krebs-Henseleit solution
      with 1 umol L(-1) atrial natriuretic peptide (n = 15) or warm Krebs-Henseleit
      solution without atrial natriuretic peptide (n = 15) in preischemic, ischemic,
      and postischemic conditions. In all rabbit hearts, global ischemia was produced
      by clamping the aortic and atrial inflow lines. Concentrations of atrial
      natriuretic peptide were measured in hearts with left ventricular dysfunction
      following ischemia, and correlated with the hypertrophic growth sustained by
      overexpression of heat-shock protein 72 microRNA-133. RESULTS: The levels of
      atrial natriuretic peptide were markedly higher in the group that received atrial
      natriuretic peptide, and strongly correlated with both band lengths of heat-shock
      protein 72 and overexpression of microRNA-133 in the hypertrophic myocyte.
      CONCLUSIONS: Perfusion levels of atrial natriuretic peptide induce increased
      expression of heat-shock protein 72 microRNA-133 in dysfunctional left ventricle.

PMID- 24585907
TI  - Staplers versus hand-sewing for pulmonary lobectomy: randomized controlled trial.
AB  - BACKGROUND: Division of the parenchymal lung for lobectomy is performed in
      patients who have an incomplete fissure. A stapler device can reduce
      postoperative air leak, but it is expensive. OBJECTIVE: to investigate the
      advantage of using a stapler, in terms of postoperative air leak and cost,
      compared to hand-sewn techniques. METHOD: A Non-blinded randomized controlled
      trial was conducted in Chiang Mai University Hospital, Thailand, from November
      15, 2011 to September 30, 2012. Fifty-three adult patients were randomized to
      undergo a hand-sewn technique (27 patients) or stapler closure (26 patients).
      RESULTS: Postoperative air leak in the stapler group was less than that in the
      hand-sewn group (7.7% vs. 29.6%, p = 0.044), and the duration of air leak in the
      stapler group was significantly shorter than that in the hand-sewn group (1.0 vs.
      13.4 days, p = 0.032). The cost of treatment was not significantly different
      between groups; however, the total cost in the stapler group was less than that
      in the hand-sewn group (mean difference 4454 Thai baht (US$144.75). CONCLUSION: A
      stapler reduces postoperative air leaks and the duration of air leaks.
      Furthermore, the total cost of treatment was comparable. Therefore, using staples
      may provide substantial financial benefits.

PMID- 24585908
TI  - Cytochrome P450-isoenzyme 1A1 in susceptibility to tobacco-related lung cancer.
AB  - BACKGROUND: Tobacco smoke contains many carcinogens that may mediate
      susceptibility to lung cancer. Cytochrome P450 isoenzyme 1A1 activity and
      expression increases several fold in lung cancer due to smoking. Finding the role
      of cytochrome P450 1A1 in susceptibility to tobacco-related lung cancer may be
      important to predict the outcome in early stage cancer, and may result in an
      improved survival rate. PATIENTS AND METHODS: This study was carried on 2 groups
      of patients: group A was 20 patients with operable smoking-related lung cancer,
      who underwent surgery at the time of diagnosis; group B was 20 nonsmokers without
      lung cancer who underwent chest exploration following road traffic accidents.
      Specimens were obtained from tumor tissue and surrounding healthy tissue in group
      A patients, and from healthy lung tissue in group B patients. These specimens
      were sent for measurement of protein content and cytochrome P450 1A1 activity.
      RESULTS: There was significantly greater tissue cytochrome P450 1A1 activity in
      group A compared to group B. Patients with stage II cancer showed significantly
      higher levels of tissue cytochrome P450 1A1 activity than those with stage I.
      There was also a significant difference in tissue cytochrome P450 1A1 activity
      between the tumor tissue and the tissue surrounding the tumor. CONCLUSION:
      Carcinogens in smoke increase cytochrome P450 1A1 activity, which might be
      considered to play a role in cigarette smoking-induced lung cancer.

PMID- 24585909
TI  - Technique for delivering large tumors in video-assisted thoracoscopic lobectomy.
AB  - BACKGROUND: The optimal technique for delivering large tumors during video
      assisted thoracoscopic lobectomy remains uncertain. METHODS: In 258 patients
      receiving video-assisted thoracoscopic lobectomy for lung cancer, techniques for
      delivering the resected lobe included complete video-assisted thoracoscopic
      lobectomy without rib spreading (n = 206, 80%), resection of a short rib segment
      (n = 9, 3%), brief rib spreading (n = 12, 5%), and conversion to a
      minithoracotomy (n = 21, 8%). In 10 (4%) patients, a novel anterior rib cutting
      technique was used: one rib at the utility port was cut near its anterior end to
      widen the intercostal space without forcible rib spreading for lobe delivery.
      RESULTS: There was no mortality or major morbidity using the anterior rib cutting
      technique, and it delivered tumors of a larger mean diameter than complete video
      assisted thoracoscopic lobectomy (5.4 +/- 3.4 vs. 2.3 +/- 1.4 cm, p = 0.017)
      whilst yielding a similar mean operation time and blood loss to the other non
      complete video-assisted thoracoscopic lobectomy techniques. The anterior rib
      cutting technique gave similar postoperative patient pain scores and analgesic
      use to complete video-assisted thoracoscopic lobectomy, and shorter mean hospital
      stay than the other non-complete video-assisted thoracoscopic lobectomy
      techniques (5.6 +/- 2.8 vs. 10.0 +/- 7.1 days, p = 0.003). CONCLUSIONS: In video
      assisted thoracoscopic lobectomy, the anterior rib cutting technique is a safe
      and feasible procedure for delivering large tumors, causing no more pain than
      complete video-assisted thoracoscopic lobectomy, and allowing faster recovery
      than other non-complete video-assisted thoracoscopic lobectomy techniques.

PMID- 24585910
TI  - Right infarction response to coronary artery bypass and the Abiomed BVS 5000.
AB  - A 57-year-old man presented with acute right ventricular infarction. A
      percutaneous coronary intervention was undertaken, but he developed shock and
      required extracorporeal membrane oxygenator support. Coronary artery bypass was
      performed, and a Abiomed BVS 5000 was implanted as a right ventricular assist
      device. Circulation gradually stabilized, and the device was removed after 5
      days. There no sign of heart failure or infection at 9 months post-surgery.

PMID- 24585911
TI  - Pseudoaneurysm of the ascending aorta 31 years after mitral valve replacement.
AB  - We describe a rare case of an ascending aortic pseudoaneurysm 31 years after
      mitral valve replacement with a Bjork-Shiley mechanical valve. The aneurysm
      presumably expanded gradually during the years following surgery. As the valve
      was functioning normally, it was left in situ while the ascending aorta was
      replaced. This report provides valuable information regarding the long-term
      nature of this patient's pseudoaneurysm, and the long-term durability of the
      Bjork-Shiley spherical valve in the mitral position. 

PMID- 24585912
TI  - Coronary artery surgery in a patient with grossly emphysematous lung.
AB  - The pedicled left internal thoracic artery graft is the mandatory conduit in
      coronary artery bypass surgery. A grossly emphysematous lung may sometimes
      present a significant problem for positioning of the pedicled left internal
      thoracic artery conduit. An inverted pedicled left internal thoracic artery graft
      (internal thoracic artery transected near its origin, thus supplied by retrograde
      flow from superior epigastric and musculophrenic arteries) might occasionally be
      the conduit of choice for those patients. 

PMID- 24585913
TI  - An unusual cause of pulmonary edema.
AB  - Primary cardiac tumors are rare malignancies. Patients may present with
      congestive cardiac failure due to intracavitary obstruction to blood flow,
      valvular dysfunction, embolic phenomena, local invasion resulting in arrhythmias,
      pericardial involvement, constitutional symptoms, or paraneoplastic syndromes. We
      describe the case of a previously fit 79-year-old woman who presented with acute
      pulmonary edema due to a large left atrial pleomorphic sarcoma causing severe
      functional mitral stenosis. She underwent palliative debulking surgery with good
      symptomatic relief. 

PMID- 24585914
TI  - Giant-cell aortitis: an unusual case of Bentall operation.
AB  - Noninfectious ascending aortitis is a very rare cause of ascending aortic
      aneurysm. We report a case of the truly fortuitous finding of this rare condition
      in a 67-year-old man operated on for an ascending aortic aneurysm associated with
      dystrophic aortic valve regurgitation. Intraoperative inspection revealed
      dissection of the aorta just above the left main coronary artery. A modified
      Bentall operation was performed. The pathological diagnosis was giant cell
      arteritis. 

PMID- 24585915
TI  - Organ donation following brain stem death after ventricular assist device
      implantation.
AB  - The availability of donor organs is the biggest limitation for lung
      transplantation, and a significant proportion of patients die on the waiting
      list. We describe a case of a 44-year-old lady who developed subarachnoid
      hemorrhage and cerebral edema on second postoperative day after left ventricular
      assist device implantation. She was declared brain stem dead 2 days later, and
      her organs were transplanted to suitable recipients on the waiting list for lung,
      liver and kidney transplantation.

PMID- 24585916
TI  - Bilateral atrial appendage aneurysms associated with atrial fibrillation.
AB  - Aneurysm of the left atrial appendage is an extremely rare anomaly. We describe
      the case of a 68-year-old man who presented with palpitation and was found to
      have a very large aneurysm located near the left atrial appendage on routine
      echocardiography. During surgery, an additional small aneurysm of the right
      atrial appendage was found. Both atrial aneurysms were resected in addition to
      mitral annuloplasty and a maze procedure. 

PMID- 24585917
TI  - Octreotide for recurrent intestinal bleeding due to ventricular assist device.
AB  - We report the case of a 64-year-old Jarvik 2000 recipient with a high risk of
      bleeding (anticoagulation treatment and acquired von Willebrand disease), who
      presented with intractable gastrointestinal hemorrhage due to severe gastric
      angiodysplasia. He was successfully treated with long-acting octreotide. 

PMID- 24585918
TI  - Right thoracotomy, off-pump, scimitar syndrome repair in infants.
AB  - Two cases of scimitar syndrome in children under one-year old are presented. Both
      were repaired through a right thoracotomy, off-pump, reimplanting the venous
      collector in the left atrium. Tips and advantages are discussed.

PMID- 24585919
TI  - Endobronchial leiomyoma in an immunocompetent four-year-old female child.
AB  - Pulmonary leiomyoma are uncommonly encountered benign mesenchymal neoplasms in
      children, usually found in immunosuppressed individuals in association with human
      immunodeficiency virus or Ebstein-Barr virus infection. We describe an
      interesting case of a 4-year-old immunocompetent girl who presented with pleural
      effusion and lung collapse secondary to endobronchial leiomyoma. She underwent a
      left thoracotomy and a left pneumonectomy for excision of the bronchial mass. 

PMID- 24585920
TI  - Congenital bronchial atresia with partial anomalous pulmonary venous return.
AB  - A 35-year-old woman with a high fever had a cystic lesion of the right lung
      including fluid and air. She was diagnosed with an infected bronchial cyst caused
      by congenital bronchial atresia with partial anomalous pulmonary venous return.
      She underwent a right upper lobectomy successfully. Patients with congenital
      bronchial atresia often have recurrent pulmonary infections with various imaging
      findings. The aberrant vein may relate to interruption of the bronchus in a
      patient with partial anomalous pulmonary venous return. Although segmental
      resection is recommended for this benign disease, lobar resection may be
      unavoidable because of adhesions or destruction of adjacent segments. 

PMID- 24585921
TI  - Unusual radiologic and histologic manifestations of primary pulmonary lymphoma.
AB  - Pulmonary parenchymal involvement in lymphoma is unusual and is reported more
      commonly in Hodgkin's disease than non-Hodgkin's lymphoma. Radiological
      appearances are manifold and may mimic other pulmonary diseases. We report the
      case of a patient with Hodgkin's disease who demonstrated multiple cavitating
      lung lesions with aberrant immunophenotypic expression of T-cell antigens. 

PMID- 24585922
TI  - Dilatation of internal mammary arteries in adult presenting aortic coarctation.

PMID- 24585923
TI  - Figure-of-eight left ventricular aneurysm.

PMID- 24585924
TI  - Pneumomediastinum after a swimming race and dental extraction.

PMID- 24585925
TI  - Endovascular stent graft for aortoesophageal fistula caused by esophageal stent.

PMID- 24585926
TI  - Aorto-right atrial fistula after aortic valve replacement.

PMID- 24585927
TI  - Atypical ascending aorta aneurysm in a young patient.

PMID- 24585928
TI  - Two-incision approach for video-assisted thoracoscopic sleeve lobectomy.
AB  - The video-assisted thoracoscopic approach for bronchoplasty procedures is not
      standardized. Although 3 to 4 incisions are usually made, with adequate surgical
      technique, the operation can be successfully carried out using only 2 incisions.
      We describe the technique of video-assisted thoracoscopic surgery for a right
      upper lobe sleeve lobectomy for a carcinoid tumor in the right upper bronchus,
      using only 2 ports. 

PMID- 24585929
TI  - Nonpsychotic mental disorder after open heart surgery.

PMID- 24585930
TI  - Topical use of tranexamic acid.

PMID- 24585931
TI  - Usefulness of J-CAPRA score for high-risk prostate cancer patients treated with
      carbon ion radiotherapy plus androgen deprivation therapy.
AB  - BACKGROUND: A novel risk assessment method, Japan Cancer of the Prostate Risk
      Assessment, has been developed based on database of patients receiving primary
      androgen deprivation therapy. To investigate the usefulness of Japan Cancer of
      the Prostate Risk Assessment for non-metastatic, high-risk prostate cancer
      patients treated with carbon ion radiotherapy plus androgen deprivation therapy.
      METHODS: Patients with non-metastatic, high-risk prostate cancer (T3, initial
      prostate specific antigen level >=20 ng/ml, and/or Gleason score >=8) were
      included. The patients were treated with carbon ion radiotherapy (the total dose
      from 57.6 Gy (relative biological effectiveness)/16 fractions to 66.0 Gy(relative
      biological effectiveness)/20 fractions), and neoadjuvant as well as adjuvant
      androgen deprivation therapy for at least 24 months. RESULTS: Four hundred and
      twenty-six patients were included with the median follow-up of 68.1 months. Of
      426, 210 (49.3%), 270 (63.4%) and 251 (58.9%) had Gleason 8-10, prostate specific
      antigen >=20 ng/ml and T3, respectively. The 10-year progression-free and cause
      specific survival rates in Japan Cancer of the Prostate Risk Assessment 1-2 group
      (76.5 and 98.9%) were significantly better than those in Japan Cancer of the
      Prostate Risk Assessment 3-6 group (52.6 and 93.1%), (P < 0.001 and P = 0.044,
      respectively). The median progression-free survivals in the Japan Cancer of the
      Prostate Risk Assessment 1-2 and 3-6 groups were 158.9 months and 125.9 months
      (95% confidence interval: 108.6-143.2 months), respectively. CONCLUSIONS: For non
      metastatic, high-risk prostate cancer patients treated with carbon ion
      radiotherapy plus androgen deprivation therapy, Japan Cancer of the Prostate Risk
      Assessment score was useful for predicting the progression-free and cause
      specific survivals.

PMID- 24585932
TI  - Phosphate homeostasis and disorders.
AB  - Recent studies of inherited disorders of phosphate metabolism have shed new light
      on the understanding of phosphate metabolism. Phosphate has important functions
      in the body and several mechanisms have evolved to regulate phosphate balance
      including vitamin D, parathyroid hormone and phosphatonins such as fibroblast
      growth factor-23 (FGF23). Disorders of phosphate homeostasis leading to hypo- and
      hyperphosphataemia are common and have clinical and biochemical consequences.
      Notably, recent studies have linked hyperphosphataemia with an increased risk of
      cardiovascular disease. This review outlines the recent advances in the
      understanding of phosphate homeostasis and describes the causes, investigation
      and management of hypo- and hyperphosphataemia. 

PMID- 24585933
TI  - Leukocyte-associated Ig-like receptor-1 is a novel inhibitory receptor for
      surfactant protein D.
AB  - The collagenous C-type lectin, SP-D, is a multitrimeric glycoprotein present at
      mucosal surfaces and is involved in host defense against infections in mammals.
      SP-D has immunomodulatory properties, but the underlying mechanisms are
      incompletely understood. SP-D contains collagen domains. LAIR-1 is an inhibitory
      immune receptor at the cell surface of various immune-competent cells that binds
      collagen. We hypothesized that the immunomodulatory functions of SP-D can be
      mediated via interactions between its collagen domain and LAIR-1. Binding assays
      show that SP-D interacts via its collagenous domain with LAIR-1 and the related
      LAIR-2. This does not affect the mannan-binding capacities of SP-D, which induces
      cross-linking of LAIR-1 in a cellular reporter assay. Functional assays show that
      SP-D inhibits the production of FcalphaR-mediated reactive oxygen via LAIR-1. Our
      studies indicate that SP-D is a functional ligand of the immune inhibitory
      receptor LAIR-1. Thus, we have identified a novel pathway for the
      immunomodulatory functions of SP-D mediated via binding of its collagenous
      domains to LAIR-1. This may provide a mechanism for the unexplained
      immunomodulatory function of the collagenous domains of SP-D. 

PMID- 24585934
TI  - On the importance of telemetric temperature sensor location during
      intraperitoneal implantation in rats.
AB  - This study aims to assess the thermal homogeneity of the intraperitoneal (IP)
      cavity and the relevance of using a fixed telemetric temperature sensor at a
      given location in studying rodents. Ten rats were intraperitoneally implanted
      with three Jonah(r) capsules each; after assessing the accuracy and reliability
      of the sensors. Two capsules were attached, one to the right iliac fossa (RIF)
      and the other to the left hypochondrium (LH), and another was placed between the
      intestines but not attached (Free). In the ex vivo condition, the differences
      between sensors and reference values remained in the range of +/-0.1. In the in
      vivo condition, each sensor enabled the observation of temperature patterns.
      However, sensor location affected mean and median temperature values while the
      rats were moving freely. Indeed, temperature data collected in the LH were 0.1
      significantly higher than those collected in the RIF and temperature data
      collected in the LH were 0.11 significantly higher than those collected with the
      Free capsules. In in vivo conditions, intra-sensor variability of temperature
      data was not affected by sensor location. Taking into account sensor accuracy,
      similar intra-sensor variability, and mean differences observed between the three
      locations, the impact of sensor location within the IP cavity could be considered
      negligible. In in vivo conditions, temperature differences between locations
      regularly exceeded +/-0.2 and reached up to 2.5. These extreme values could be
      explained by behavioral factors such as food or water intake. Finally,
      considering the good thermal homogeneity of the IP cavity and possible adverse
      consequences of sensor attachment, it seems better to let sensors range free
      within the cavity. 

PMID- 24585935
TI  - Refinement of tourniquet-induced peripheral ischemia/reperfusion injury in rats:
      comparison of 2 h vs 24 h reperfusion.
AB  - Prolonged ischemia of skeletal muscle tissue, followed by reperfusion, leads to
      ischemia/reperfusion injury (IRI), which is a feared local and systemic
      inflammatory reaction. With respect to the 3Rs, we wanted to determine which
      parameters for assessment of IRI require a reperfusion time of 24 h and for which
      2 h of reperfusion are sufficient. Rats were subjected to 3 h of hind limb
      ischemia and 2 h or 24 h of reperfusion. Human plasma derived C1 inhibitor was
      used as a drug to prevent reperfusion injury. For 2 h of reperfusion the rats
      stayed under anesthesia throughout (severity grade 1), whereas for 24 h they were
      awake under analgesia during reperfusion (grade 2). The femoral artery was
      clamped and a tourniquet was placed, under maintenance of venous return. C1
      esterase inhibitor was systemically administered 5 min before the induction of
      ischemia. No differences in local muscle edema formation and depositions of
      immunoglobulin G and immunoglobulin M were observed between 2 h and 24 h (P >
      0.05), whereas lung edema was only observed after 24 h. Muscle viability was
      significantly lower after 24 h vs 2 h reperfusion (P < 0.05). Increased plasma
      creatine kinase (CK)-MM and platelet-derived growth factor (PDGF)-bb could be
      detected after 2 h, but not after 24 h of reperfusion. By contrast, depositions
      of C3b/c and fibrin in muscle were only detected after 24 h (P < 0.001). In
      conclusion, for a first screening of drug candidates to reduce IRI, 2 h
      reperfusions are sufficient, and these reduce the severity of the animal
      experiment. Twenty-four-hour reperfusions are only needed for in-depth analysis
      of the mechanisms of IRI, including lung damage. 

PMID- 24585936
TI  - IL-18 stimulates B-type natriuretic peptide synthesis by cardiomyocytes in vitro
      and its plasma levels correlate with B-type natriuretic peptide in non-overloaded
      acute heart failure patients.
AB  - BACKGROUND: An altered IL-18 pathway in heart failure (HF) has recently been
      described and this cytokine was shown to be of clinical and prognostic utility.
      Cardiomyocytes are a target of this cytokine which exerts inflammatory,
      hypertrophic, and profibrotic activities. B-type natriuretic peptide is a cardiac
      hormone produced in response to cardiac filling to regulate cardiovascular
      homeostasis. The aim of the study was to verify the ability of IL-18 to induce B
      type natriuretic peptide synthesis in vitro and to analyse the relationship
      between these two molecules in plasma in vivo from acute HF patients. METHODS AND
      RESULTS: We demonstrated the ability of IL-18 to directly stimulate a murine
      cardiomyocyte cell line to express the B-type natriuretic peptide gene,
      synthesize the relative protein through a PI3K-AKT-dependent transduction, and
      induce a cell secretory phenotype with B-type natriuretic peptide release. A
      correlation between IL-18 and B-type natriuretic peptide plasma levels was found
      in non-overloaded acute HF patients, and in subgroups of acute HF patients with
      diabetes and coronary artery disease. Acute HF patients with renal failure had
      significantly higher IL-18 plasma levels than patients without. IL-18 plasma
      levels were correlated with C-reactive protein plasma levels. CONCLUSIONS: This
      study provides the first evidence of the ability of IL-18 to induce B-type
      natriuretic peptide synthesis in vitro and outlines the relationship between the
      two molecules in acute HF patients with an ongoing inflammatory status.

PMID- 24585937
TI  - Acute Cardiac Care 2013.

PMID- 24585938
TI  - Prevalence of spontaneous coronary artery dissection in patients with acute
      coronary syndrome.
AB  - AIMS: Spontaneous coronary artery dissection (SCAD) found typically in young
      females without classical coronary risk factors is thought to be a very rare
      cause of acute coronary syndrome (ACS). The prevalence of SCAD in ACS subjects
      has been unclear, probably due to the nature of coronary angiography. The aim of
      this study was to use optical coherence tomography (OCT) to investigate the
      prevalence of SCAD in ACS. METHODS AND RESULTS: This study consisted of 326
      patients with ACS (with or without ST-segment elevation) who underwent OCT to
      explore the entire culprit artery. According to OCT findings, patients were
      divided into a SCAD, a plaque rupture (PR), and a non-SCAD/non-PR group. OCT
      revealed 13 (4.0%) SCADs and 160 (49.1%) plaque ruptures in ACS subjects. The
      percentage of females versus males was greater in the SCAD group (SCAD: 53.8% vs.
      PR: 20.0% vs. non-SCAD/non-PR: 23.5%, p=0.02) while no difference was observed in
      age (SCAD: 67.3+/-13.3 vs. PR: 66.5+/-11.1 vs. non-SCAD/non-PR: 67.0+/-10.5,
      p=0.90). The prevalence of dyslipidemia (SCAD: 30.8% vs. PR: 63.8% vs. non
      SCAD/non-PR: 67.5%, p=0.03) and current smoking (SCAD: 7.7% vs. PR: 57.9% vs. non
      SCAD/non-PR: 59.7%, p<0.01) were significantly lower in the SCAD group.
      CONCLUSIONS: SCAD is not a rare cause for ACS, especially in females without
      classical coronary risk factors.

PMID- 24585939
TI  - Coronary spasm and myocardial bridging: an elusive pathophysiological mechanism
      leading to apical ballooning syndrome?
AB  - Apical ballooning syndrome or Takotsubo-like cardiomyopathy is an acute syndrome
      characterized by normal or near-normal coronary arteries, regional wall motion
      abnormalities that extend beyond a single coronary vascular bed and, often, a
      precipitating stressor. We observed a case of an elderly lady with Takotsubo-like
      left ventricular dysfunction in whom both left anterior descending artery and
      diagonal branch coronary artery reversible spasm and myocardial bridging were
      demonstrated at the time of acute cardiac catheterization. It is a common
      observation that a combination of multiple pathophysiological mechanisms may
      produce a clinically similar picture. We believe that reversible, yet extreme,
      spasticity elicited at the level of myocardial bridging and involving a territory
      beyond a single coronary branch may explain in this case a functional phenomenon,
      namely the Takotsubo-shaped dysfunction of the left ventricle, which is more
      commonly observed in women with totally normal coronary arteries after
      exaggerated sympathetic stimulation.

PMID- 24585940
TI  - Transcatheter closure of a traumatic ventricular septum defect resulting from a
      stab wound.
AB  - A 25-year-old man with a ventricular septal defect resulting from a stab wound to
      his chest was admitted to our hospital. Because of extensive comorbidity and
      favourable location, transcatheter closure with an Amplatzer device was preferred
      over surgical repair. Ventricular septal defects are an uncommon complication of
      cardiac trauma, but when they do occur from this cause, they often have more
      dramatic consequences. Transcatheter closure is an attractive, less-invasive
      alternative in patients with increased surgical risk, multiple previous surgical
      interventions, or poorly accessible defects. 

PMID- 24585941
TI  - Postoperative takotsubo cardiomyopathy: an illustration of the
      electrocardiographic features that raise suspicion for takotsubo.
AB  - Takotsubo cardiomyopathy is an increasingly recognized clinical disorder
      mimicking acute coronary syndrome. It is usually preceded by physical or
      emotional stress and recovery of the left ventricular systolic function occurs in
      most cases within 1-4 weeks. Takotsubo cardiomypathy can masquerade as ST-segment
      elevation myocardial infarction when chest pain, ST-segment elevation, and high
      cardiac biomarkers coexist. ST-segment elevation is encountered in approximately
      half of the cases of takotsubo cardiomyopathy and its pattern is
      indistinguishable at times from ST-segment elevation myocardial infarction.
      However, several electrocardiographic criteria have been shown to characterize
      takotsubo cardiomyopathy. Awareness of these electrocardiographic features has
      several diagnostic and therapeutic implications. Nevertheless, these
      electrocardiographic criteria alone cannot reliably differentiate between both
      entities, and the diagnosis of takotsubo cardiomyopathy is only established after
      coronary angiography confirms the absence of occlusive coronary artery disease
      and the characteristic apical ballooning is evident on left ventriculogram (in
      the case of the apical form). Herein, we present a case of postoperative
      takotsubo cardiomyopathy and discuss the various electrocardiographic features
      that raise suspicion for this transient cardiac syndrome.

PMID- 24585942
TI  - Weekend compared with weekday presentation does not affect outcomes of patients
      presenting with non-ST elevation acute coronary syndrome.
AB  - AIM: In non-ST elevation acute coronary syndromes (NSTEACS), early invasive
      management improves survival. However, since treatment strategies are urgent, not
      emergent, decisions to postpone invasive management due to weekend admission
      could affect outcome. METHODS: Using the Alberta Provincial Project for Outcomes
      Assessment in Coronary Heart Disease (APPROACH), a population-based registry
      capturing all cardiac admissions in southern Alberta, we compared time to cardiac
      catheterization, modality of revascularization, and crude and risk-adjusted
      mortality for NSTEACS patients presenting on weekends vs. weekdays. From 1 April
      2005 to 31 October 2010, 11,981 patients were admitted to care facilities in
      southern Alberta (32.1% on weekends and 67.9% on weekdays). RESULTS: Baseline
      characteristics were similar. Mean time to cardiac catheterization was 67.2 h in
      the weekend group, compared to 62.4 h in the weekday group (p=0.03), with 34.7%
      of weekend and 45.1% of weekday patients receiving catheterization within 24 h of
      admission (p<0.0001), and 49.1 and 59.9%, respectively, within 48 h (p=0.002).
      Mortality at 30 days was 2.2% in the weekend group compared to 2.0% in the
      weekday group (p=0.58). The crude hazard ratio (HR) for 30-day mortality in the
      weekend group was 1.08 (95% CI 0.83-1.40). After adjusting for baseline risk
      factors, the HR for mortality remained non-significant (HR 1.06, 95% CI 0.82
      1.38). Mortality at 1 year was also similar. CONCLUSIONS: In a large unselected
      population of NSTEACS patients, weekend admission was associated with modest
      delays (4.8 h) in time to catheterization, but not with increased 30-day or 1
      year mortality.

PMID- 24585943
TI  - An international age- and gender-controlled model for the Spinal Cord Injury
      Ability Realization Measurement Index (SCI-ARMI).
AB  - Background. A quadratic formula of the Spinal Cord Injury Ability Realization
      Measurement Index (SCI-ARMI) has previously been published. This formula was
      based on a model of Spinal Cord Independence Measure (SCIM95), the 95th
      percentile of the SCIM III values, which correspond with the American Spinal
      Injury Association Motor Scores (AMS) of SCI patients. Objective. To further
      develop the original formula. Setting. Spinal cord injury centers from 6
      countries and the Statistical Laboratory, Tel-Aviv University, Israel. Methods.
      SCIM95 of 661 SCI patients was modeled, using a quantile regression with or
      without adjustment for age and gender, to calculate SCI-ARMI values. SCI-ARMI
      gain during rehabilitation and its correlations were examined. Results. A new
      quadratic SCIM95 model was created. This resembled the previously published
      model, which yielded similar SCIM95 values in all the countries, after adjustment
      for age and gender. Without this adjustment, however, only 86% of the non-Israeli
      SCIM III observations were lower than those SCIM95 values (P < .0001). Adding the
      variables age and gender to the new model affected the SCIM95 value significantly
      (P < .04). Adding country information did not add a significant effect (P > .1).
      SCI-ARMI gain was positive (38.8 +/- 22 points, P < .0001) and correlated weakly
      with admission age and AMS. Conclusions. The original quadratic SCI-ARMI formula
      is valid for an international population after adjustment for age and gender. The
      new formula considers more factors that affect functional ability following SCI. 

PMID- 24585944
TI  - Diffusion-weighted MRI compared to FDG PET/CT for assessment of early treatment
      response in lymphoma.
AB  - BACKGROUND: 18F fluoro-deoxyglucose (FDG) positron emission tomography / computed
      tomography (PET/CT) is a well-recognized diagnostic tool used for staging and
      monitoring of therapy response for lymphomas. During the past decade diffusion
      weighted (DW) magnetic resonance imaging (MRI) is increasingly being included in
      the assessment of tumor response for various cancers. PURPOSE: To compare the
      change in maximum standardized uptake value (DeltaSUVmax) from FDG PET/CT with
      the change in apparent diffusion coefficient (DeltaADC) from DW MRI after
      initiation of the first cycle of chemotherapy in patients with Hodgkin's lymphoma
      (HL) and in patients with diffuse large B-cell lymphoma (DLBCL). MATERIAL AND
      METHODS: Twenty-seven consecutive patients with histologically proven lymphoma
      and lymphomatous lymph nodes (LLN) of the neck (19 with HL, 8 with DLBCL)
      underwent FDG PET/CT and MRI of the neck before and after initiation of the first
      cycle of chemotherapy. The mean time interval from initiation of chemotherapy to
      imaging was 19 days and 2 days for FDG PET/CT and MRI, respectively. For each
      patient DeltaSUVmax, DeltaADC, and change in volume of the same LLN were
      compared. RESULTS: There was a significant mean decrease of SUVmax by 70%, but no
      significant change in ADC. There was no significant reduction in LLN volume.
      CONCLUSION: There was no significant correlation between DeltaSUVmax and
      DeltaADC. Thus, our data do not support that FDG PET/CT can be replaced by early
      DW MRI for response evaluation in lymphoma patients.

PMID- 24585945
TI  - Abstracts of the Heavy Ion Therapy and Space Radiation Symposium 2013
      (HITSRS2013), May 15th to 18th, 2013, Chiba, Japan.

PMID- 24586019
TI  - Intestinal adaptation following resection.
AB  - Intestinal adaptation is a natural compensatory process that occurs following
      extensive intestinal resection, whereby structural and functional changes in the
      intestine improve nutrient and fluid absorption in the remnant bowel. In animal
      studies, postresection structural adaptations include bowel lengthening and
      thickening and increases in villus height and crypt depth. Functional changes
      include increased nutrient transporter expression, accelerated crypt cell
      differentiation, and slowed transit time. In adult humans, data regarding
      adaptive changes are sparse, and the mechanisms underlying intestinal adaptation
      remain to be fully elucidated. Several factors influence the degree of intestinal
      adaptation that occurs post resection, including site and extent of resection,
      luminal stimulation with enteral nutrients, and intestinotrophic factors. Two
      intestinotrophic growth factors, the glucagon-like peptide 2 analog teduglutide
      and recombinant growth hormone (somatropin), are now approved for clinical use in
      patients with short bowel syndrome (SBS). Both agents enhance fluid absorption
      and decrease requirements for parenteral nutrition (PN) and/or intravenous fluid.
      Intestinal adaptation has been thought to be limited to the first 1-2 years
      following resection in humans. However, recent data suggest that a significant
      proportion of adult patients with SBS can achieve enteral autonomy, even after
      many years of PN dependence, particularly with trophic stimulation. 

PMID- 24586020
TI  - Myostatin tilts the balance between skeletal muscle size, function and
      metabolism.

PMID- 24586021
TI  - Introduction: myometrial physiology--time to translate?

PMID- 24586023
TI  - It's time for change; commentary in response to feature article by Halpin et al.
AB  - It is essential that we re-examine the way new drugs for life-threatening
      illnesses are assessed and regulated. The time taken to approve lifesaving
      medicines for general use outside of clinical trials is prohibitively slow;
      people are needlessly dying. The bioethics community should be at the forefront
      of change. In particular, the rigid adherence to Evidence Based Medicine (EBM)
      has become irrational. New regulatory frameworks are being proposed, including
      that of adaptive licensing. Whereas the current model uses a one-point-in-time,
      all-or-nothing system of regulation, adaptive licensing allows for progressive
      access to a new drug during the approval process. Indeed this may be the first
      instance where the contemporary practice of EBM needs to be abandoned due to
      inherent inefficiencies. In response to the inefficiencies of the current system,
      a collaboration of stakeholders has established NEWDIGS (NEW Drug Development
      ParadIGmS). The Feature Article by Halpin and colleagues, on which this
      Commentary is based, gives a sophisticated survey of relevant bioethical issues.
      In addition this Commentary outlines a novel bioethical model to align with
      proposed new regulatory frameworks: a distributive-benefit-at-equilibrium model. 

PMID- 24586024
TI  - "Nurses, docs, and drugs": interprofessional facilitation to implement opioid
      risk mitigation within the patient-centered medical home.

PMID- 24586025
TI  - Health systems engineering fellowship: curriculum and program development.
AB  - Industrial engineering and related disciplines have been used widely in
      improvement efforts in many industries. These approaches have been less commonly
      attempted in health care. One factor limiting application is the limited
      workforce resulting from a lack of specific education and professional
      development in health systems engineering (HSE). The authors describe the
      development of an HSE fellowship within the United States Department of Veterans
      Affairs, Veterans Health Administration (VA). This fellowship includes a novel
      curriculum based on specifically established competencies for HSE. A 1-year HSE
      curriculum was developed and delivered to fellows at several VA engineering
      resource centers over several years. On graduation, a majority of the fellows
      accepted positions in the health care field. Challenges faced in developing the
      fellowship are discussed. Advanced educational opportunities in applied HSE have
      the potential to develop the workforce capacity needed to improve the quality of
      health care. 

PMID- 24586026
TI  - Patient-reported reasons for emergency department visits in the urban Medicaid
      population.
AB  - This study investigated patient-reported reasons for treat-and-release emergency
      department (ED) visits by Medicaid beneficiaries. An in-house-designed
      educational survey was conducted that consisted of 3 components: patient's
      health, patient's primary care, and patient's ED visit. An ED patient was asked
      an open-ended question about the reason for a recent ED visit. The patient's
      answer was classified into 1 of 3 types: health care service delivery issues,
      population behavior issues, and unavoidable ED visits. Among 2711 ED visits, 56%
      were related to health care service delivery issues (ie, access to care, primary
      care provider [PCP] availability), 2% were associated with population behavior
      issues, and 42% were unavoidable. For those ED visits related to PCP
      unavailability, 72% occurred during off-hours or weekends and 28% were because of
      no timely PCP appointments. The findings suggest that inadequate access to
      primary care is a major cause of potentially avoidable ED utilization in the
      Medicaid population. 

PMID- 24586027
TI  - Relationship between glycoprotein IIIa platelet receptor gene polymorphism and
      coronary artery disease.
AB  - Glycoprotein IIb/IIIa (GP IIb/IIIa) is a key receptor for platelet aggregation
      and adhesion. We investigated whether a single-nucleotide polymorphism of GP IIIa
      subunit (Leu33Pro-PlA(1)/PlA(2) allele) is associated with the extent of coronary
      artery disease (CAD) in a consecutive cohort of 1518 patients undergoing coronary
      angiography. Significant CAD was defined as at least a stenosis >50% and severe
      CAD as left main disease and/or trivessel disease. Additionally, carotid intima
      media thickness (cIMT) was evaluated in 339 patients. The PlA(2) allele was
      observed in 458 (30.2%) patients and associated with hypercholesterolemia (P =
      .03). No difference was observed in the prevalence of CAD (72.6% vs 70.1%, P =
      .29; adjusted odds ratio, OR [95% confidence interval, CI] = 0.85 [0.67-1.08], P
      = .19) and severe CAD (27.5% vs 26.5%, adjusted OR [95% CI] = 0.93 [0.72-1.19], P
      = .55). Furthermore, Leu33Pro polymorphism did not affect cIMT and the prevalence
      of carotid plaques. Therefore, this polymorphism cannot be regarded as a risk
      factor for coronary or carotid atherosclerosis. 

PMID- 24586029
TI  - chlB requirement for chlorophyll biosynthesis under short photoperiod in
      Marchantia polymorpha L.
AB  - Chlorophylls (Chls) play pivotal roles in energy absorption and transduction and
      also in charge separation in reaction centers in all photosynthetic organisms. In
      Chl biosynthesis steps, only a step for the enzymatic reduction of
      protochlorophyllide (Pchlide) to chlorophyllide (Chlide) is mediated by both
      nuclear- and chloroplast-encoded genes in land plants. Many plants encode the
      genes for light-dependent Pchlide reductase (LPOR) and light-independent Pchlide
      reductase (DPOR) in the nucleus and chloroplast genome, respectively. During the
      diversification of land plants, the reduction step of Pchlide to Chlide has
      become solely dependent on LPOR, and the genes for DPOR have been lost from
      chloroplast genome. It remains unclear why DPOR persists in some land plants, how
      they were eliminated from chloroplast genomes during the diversification of land
      plants, and under what environmental conditions DPOR was required. We demonstrate
      that DPOR is functional in liverwort (Marchantia polymorpha L.) and plays an
      important role in Chl biosynthesis. Having established a plastid transformation
      system in liverwort, we disrupted chlB, which encodes a subunit of DPOR in the M.
      polymorpha chloroplast genome. Morphological and Chl content analysis of a chlB
      mutant grown under different photoperiods revealed that DPOR is particularly
      required for Chl biosynthesis under short-day conditions. Our findings suggest
      that an environmental condition in the form of photoperiod is an important factor
      that determines the loss or retention of chloroplast-encoded genes mediating
      Pchlide reduction to Chlide. 

PMID- 24586028
TI  - Evolutionary history of wild barley (Hordeum vulgare subsp. spontaneum) analyzed
      using multilocus sequence data and paleodistribution modeling.
AB  - Studies of Hordeum vulgare subsp. spontaneum, the wild progenitor of cultivated
      barley, have mostly relied on materials collected decades ago and maintained
      since then ex situ in germplasm repositories. We analyzed spatial genetic
      variation in wild barley populations collected rather recently, exploring
      sequence variations at seven single-copy nuclear loci, and inferred the
      relationships among these populations and toward the genepool of the crop. The
      wild barley collection covers the whole natural distribution area from the
      Mediterranean to Middle Asia. In contrast to earlier studies, Bayesian assignment
      analyses revealed three population clusters, in the Levant, Turkey, and east of
      Turkey, respectively. Genetic diversity was exceptionally high in the Levant,
      while eastern populations were depleted of private alleles. Species distribution
      modeling based on climate parameters and extant occurrence points of the taxon
      inferred suitable habitat conditions during the ice-age, particularly in the
      Levant and Turkey. Together with the ecologically wide range of habitats, they
      might contribute to structured but long-term stable populations in this region
      and their high genetic diversity. For recently collected individuals, Bayesian
      assignment to geographic clusters was generally unambiguous, but materials from
      genebanks often showed accessions that were not placed according to their assumed
      geographic origin or showed traces of introgression from cultivated barley. We
      assign this to gene flow among accessions during ex situ maintenance.
      Evolutionary studies based on such materials might therefore result in wrong
      conclusions regarding the history of the species or the origin and mode of
      domestication of the crop, depending on the accessions included. 

PMID- 24586030
TI  - Predominant and substoichiometric isomers of the plastid genome coexist within
      Juniperus plants and have shifted multiple times during cupressophyte evolution.
AB  - Most land plant plastomes contain two copies of a large inverted repeat (IR) that
      promote high-frequency homologous recombination to generate isomeric genomic
      forms. Among conifer plastomes, this canonical IR is highly reduced in Pinaceae
      and completely lost from cupressophytes. However, both lineages have acquired
      short, novel IRs, some of which also exhibit recombinational activity to generate
      genomic structural diversity. This diversity has been shown to exist between, and
      occasionally within, cupressophyte species, but it is not known whether multiple
      genomic forms coexist within individual plants. To examine the recombinational
      potential of the novel cupressophyte IRs within individuals and between species,
      we sequenced the plastomes of four closely related species of Juniperus. The four
      plastomes have identical gene content and genome organization except for a large
      36 kb inversion between approximately 250 bp IR containing trnQ-UUG. Southern
      blotting showed that different isomeric versions of the plastome predominate
      among individual junipers, whereas polymerase chain reaction and high-throughput
      read-pair mapping revealed the substoichiometric presence of the alternative
      isomeric form within each individual plant. Furthermore, our comparative genomic
      studies demonstrate that the predominant and substoichiometric arrangements of
      this IR have changed several times in other cupressophytes as well. These results
      provide compelling evidence for substoichiometric shifting of plastomic forms
      during cupressophyte evolution and suggest that substoichiometric shifting
      activity in plastid genomes may be adaptive. 

PMID- 24586031
TI  - Sequential, concomitant and hybrid first-line therapies for Helicobacter pylori
      eradication: a prospective randomized study.
AB  - Helicobacter pylori eradication remains a challenge for physicians. Sequential,
      concomitant and the hybrid regimens have been proposed as novel, more effective
      therapies. We compare the efficacy of these therapies. Dyspeptic patients
      referred for upper endoscopy with H. pylori infection were enrolled. Patients
      were randomized to receive: (a) sequential therapy - 20 mg omeprazole and 1 g
      amoxicillin for 5 days, followed by 20 mg omeprazole, 500 mg clarithromycin and
      500 mg tinidazole for the successive 5 days; (b) concomitant therapy - 20 mg
      omeprazole, 1 g amoxicillin, 500 mg clarithromycin and 500 mg tinidazole for
      either 5 days (5 day concomitant) or 14 days (14 day concomitant); or (c) hybrid
      therapy - 20 mg omeprazole and 1 g amoxicillin for 7 days, followed by 20 mg
      omeprazole, 1 g amoxicillin, 500 mg clarithromycin and 500 mg tinidazole for the
      successive 7 days. All drugs were given twice daily. Bacterial eradication was
      checked by using a [(13)C]urea breath test. In 'intention-to-treat' analysis,
      sequential therapy achieved the highest eradication rate, which was higher than
      that of 5 day concomitant therapy (90  vs 78.1 %; P = 0.02). The success rate did
      not statistically differ among the sequential and either 14 day concomitant (90 
      vs 86.3 %; P = not significant) or hybrid therapies (90  vs 82.7 %; P = not
      significant). The 10 day sequential, 14 day concomitant and 14 day hybrid
      therapies, but not the 5 day concomitant regimen, achieved similarly high
      eradication rates. The lower therapeutic cost coupled with the lower number of
      tablets needed would favour the sequential therapy as the first-line H. pylori
      treatment in clinical practice.

PMID- 24586033
TI  - Detection of benzalkonium chloride resistance in community environmental isolates
      of staphylococci.
AB  - We isolated a total of 653 strains from 64 community environmental samples in
      Massachusetts, USA. Among these isolates, 9.65 % (63 strains) were benzalkonium
      chloride (BC)-resistant staphylococci. All BC-resistant strains were collected
      from surfaces upon which antibacterial wipes or antibacterial sprays containing
      0.02-0.12 % BC had frequently been used in the fitness centres. However, isolates
      from surfaces upon which antibacterial wipes or antibacterial sprays had not been
      used were all sensitive to BC. All BC-resistant strains were also resistant to
      erythromycin, penicillin and ampicillin. In addition, 51 strains showed
      resistance to cetyltrimethylammonium bromide (CTAB), 15 strains showed resistance
      to chloramphenicol, 12 strains showed resistance to ciprofloxacin and four
      strains showed resistance to meticillin. Resistance gene analysis demonstrated
      that 41 strains contained qacA/B, 30 strains had qacC, 25 strains contained qacG,
      16 strains had qacH and eight strains contained qacJ. These data indicate that
      application of BC is associated with environmental staphylococcal antimicrobial
      resistance.

PMID- 24586035
TI  - Resistance to oxidative stress via regulating siderophore-mediated iron
      acquisition by the citrus fungal pathogen Alternaria alternata.
AB  - The ability of the necrotrophic fungus Alternaria alternata to detoxify reactive
      oxygen species (ROS) is crucial for pathogenesis to citrus. We report regulation
      of siderophore-mediated iron acquisition and ROS resistance by the NADPH oxidase
      (NOX), the redox activating yes-associated protein 1 (YAP1) regulator, and the
      high-osmolarity glycerol 1 (HOG1) mitogen-activated protein kinase (MAPK). The A.
      alternata nonribosomal peptide synthetase (NPS6) is essential for the
      biosynthesis of siderophores, contributing to iron uptake under low-iron
      conditions. Fungal strains impaired for NOX, YAP1, HOG1 or NPS6 all display
      increased sensitivity to ROS. Exogenous addition of iron at least partially
      rescues ROS sensitivity seen for NPS6, YAP1, HOG1, and NOX mutants. Importantly,
      expression of the NPS6 gene and biosynthesis of siderophores are regulated by
      NOX, YAP1 and HOG1, supporting a functional link among these regulatory pathways.
      Although iron fully rescues H2O2 sensitivity seen in mutants impaired for the
      response regulator SKN7, neither expression of NPS6 nor biosynthesis of
      siderophores is controlled by SKN7. Our results indicate that the acquisition of
      environmental iron has profound effects on ROS detoxification. 

PMID- 24586037
TI  - Editorial: Yersinia pestis survives in neutrophils and sends a PS to macrophages:
      bon appetit!

PMID- 24586036
TI  - Diversification of CRISPR within coexisting genotypes in a natural population of
      the bloom-forming cyanobacterium Microcystis aeruginosa.
AB  - The clustered regularly interspaced short palindromic repeat (CRISPR) confers
      adaptive immunity against phages via sequence fragments (spacers) derived from
      mobile genetic elements (MGEs), thus serving as a memory of past host-phage co
      evolution. To understand co-evolutionary dynamics in natural settings, we
      examined CRISPR diversity in 94 isolates of Microcystis aeruginosa from a small
      eutrophic pond. Fifty-two isolates possessed the CRISPR and were classified into
      22 different CRISPR-related genotypes, suggesting stable coexistence of multiple
      genotypes with different phage susceptibility. Seven CRISPR-related genotypes
      showed variation of spacers at the leader-end of the CRISPR, indicating active
      spacer addition from MGEs. An abundant phylotype (based on the internal
      transcribed spacer of the rRNA gene) contained different CRISPR spacer genotypes
      with the same CRISPR-associated cas2 gene. These data suggest that selective
      phage infection and possibly plasmid transfer may contribute to maintenance of
      multiple genotypes of M. aeruginosa and that rapid co-evolution within a host
      phage combination may be driven by increased contact frequency. Forty-two
      isolates lacked detectable CRISPR loci. Relative abundance of the CRISPR-lacking
      genotypes in the population suggests that CRISPR loss may be selected for
      enhanced genetic exchange. 

PMID- 24586038
TI  - Editorial: GCN5 opens the door for the IRF-4-mediated cascade of B cell
      differentiation.

PMID- 24586032
TI  - Analysis of gene expression changes in Trichophyton rubrum after skin
      interaction.
AB  - Trichophyton rubrum, an anthropophilic and cosmopolitan fungus, is the most
      common agent of superficial mycoses. In this study, T. rubrum infection was
      modelled by adding human skin sections to a limited medium containing glucose and
      cDNA microarrays were used to monitor T. rubrum gene expression patterns on a
      global level. We observed that exposure to human skin resulted in upregulation of
      the expression levels of T. rubrum genes related to many cellular and biological
      processes, including transcription and translation, metabolism and secondary
      transport, the stress response, and signalling pathways. These results provide a
      reference set of T. rubrum genes whose expression patterns change upon infection
      and reveal previously unknown genes that most likely correspond to proteins that
      should be considered as virulence factor candidates and potential new drug
      targets for T. rubrum infection.

PMID- 24586039
TI  - Anomalous aortic origin of coronary arteries: 'anatomical' surgical repair.
AB  - Anomalous aortic origin of coronary arteries (left coronary from right sinus or
      right coronary from left sinus) is a rare congenital defect, which carries a high
      risk of sudden cardiac death. The risk is particularly high when the
      interarterial course between the great arteries has an intramural segment, or is
      hypoplastic/stenotic, or has an abnormal orifice. Various surgical techniques
      have been used, including coronary artery bypass grafting, pulmonary artery
      translocation, partial or complete unroofing of the intramural course and patch
      enlargement of the interarterial course. We favour 'anatomical' repair that
      creates an enlarged neo-ostium into the appropriate sinus, eliminates completely
      the intramural segment and restores a normal angle of take-off. Reimplantation of
      the anomalous coronary artery may be indicated in variants without an intramural
      course. Surgical correction is mandatory for symptomatic and asymptomatic
      patients with evidence of myocardial ischaemia under stress; it is recommended in
      asymptomatic patients with high-risk variants (anomalous left coronary artery
      with the intramural course), particularly in young patients with strenuous
      activities. 

PMID- 24586040
TI  - Regulation of the Ca(2+)-independent phospholipase A2 in liver mitochondria by
      changes in the energetic state.
AB  - The effect of electron transport chain redox status on activity of the
      mitochondrial Ca(2+)-independent phospholipase A2 (iPLA2) has been examined. When
      oxidizing NAD-linked substrates, the enzyme is not active unless deenergization
      occurs. Uncoupler, rotenone, antimycin A, and cyanide are equally effective at
      upregulating the enzyme, while oligomycin is ineffective. Thenoyltrifluoroacetone
      causes deenergization and activates the enzyme, but only if succinate is the
      respiratory substrate. These findings show that the mitochondrial iPLA2 responds
      to the energetic state overall, rather than to the redox status of individual
      electron transport chain complexes. With NAD-linked substrates, and using
      rotenone to deenergize, iPLA2 activation can be reversed by adding succinate to
      reestablish a membrane potential. For this purpose, ascorbate plus N,N,N'N'
      tetramethyl-phenylenediamine can be used instead of succinate and is equally
      effective. With succinate as substrate, the membrane potential can be reduced in
      a graded and stable fashion by adding increasing concentrations of malonate,
      which is a competitive inhibitor of succinate utilization. A partial and stable
      activation of the iPLA2 accompanies partial deenergization. These findings
      suggest that in addition to the several functions that have been proposed, the
      mitochondrial iPLA2 may help to coordinate local capillary blood flow with
      changing energy demands.

PMID- 24586041
TI  - Structural analysis of the PSD-95 cluster by electron tomography and CEMOVIS: a
      proposal for the application of the genetically encoded metallothionein tag.
AB  - Postsynaptic density-95 (PSD-95) accumulates at excitatory postsynapses and plays
      important roles in the clustering and anchoring of numerous proteins at the PSD.
      However, a detailed ultrastructural analysis of clusters exclusively consisting
      of PSD-95 has never been performed. Here, we employed a genetically encoded tag,
      three tandem repeats of metallothionein (3MT), to study the structure of PSD-95
      clusters in cells by electron tomography and cryo-electron microscopy of vitreous
      sections. We also performed conventional transmission electron microscopy (TEM).
      Cultured hippocampal neurons expressing a fusion protein of PSD-95 coupled to 3MT
      (PDS-95-3MT) were incubated with CdCl2 to result in the formation of Cd-bound PSD
      95-3MT. Two types of electron-dense deposits composed of Cd-bound PSD-95-3MT were
      observed in these cells by TEM, as reported previously. Electron tomography
      revealed the presence of membrane-shaped structures representing PSD-95 clusters
      at the PSD and an ellipsoidal structure located in the non-synaptic cytoplasm. By
      TEM, the PSD-95 clusters appeared to be composed of a number of dense cores. In
      frozen hydrated sections, these dense cores were also found beneath the
      postsynaptic membrane. Taken together, our findings suggest that dense cores of
      PSD-95 aggregate to form the larger clusters present in the PSD and the non
      synaptic cytoplasm. 

PMID- 24586042
TI  - The leucine-rich repeat receptor-like kinase BRASSINOSTEROID INSENSITIVE1
      ASSOCIATED KINASE1 and the cytochrome P450 PHYTOALEXIN DEFICIENT3 contribute to
      innate immunity to aphids in Arabidopsis.
AB  - The importance of pathogen-associated molecular pattern-triggered immunity (PTI)
      against microbial pathogens has been recently demonstrated. However, it is
      currently unclear if this layer of immunity mediated by surface-localized pattern
      recognition receptors (PRRs) also plays a role in basal resistance to insects,
      such as aphids. Here, we show that PTI is an important component of plant innate
      immunity to insects. Extract of the green peach aphid (GPA; Myzus persicae)
      triggers responses characteristic of PTI in Arabidopsis (Arabidopsis thaliana).
      Two separate eliciting GPA-derived fractions trigger induced resistance to GPA
      that is dependent on the leucine-rich repeat receptor-like kinase BRASSINOSTEROID
      INSENSITIVE1-ASSOCIATED KINASE1 (BAK1)/SOMATIC-EMBRYOGENESIS RECEPTOR-LIKE
      KINASE3, which is a key regulator of several leucine-rich repeat-containing PRRs.
      BAK1 is required for GPA elicitor-mediated induction of reactive oxygen species
      and callose deposition. Arabidopsis bak1 mutant plants are also compromised in
      immunity to the pea aphid (Acyrthosiphon pisum), for which Arabidopsis is
      normally a nonhost. Aphid-derived elicitors induce expression of PHYTOALEXIN
      DEFICIENT3 (PAD3), a key cytochrome P450 involved in the biosynthesis of
      camalexin, which is a major Arabidopsis phytoalexin that is toxic to GPA. PAD3 is
      also required for induced resistance to GPA, independently of BAK1 and reactive
      oxygen species production. Our results reveal that plant innate immunity to
      insects may involve early perception of elicitors by cell surface-localized PRRs,
      leading to subsequent downstream immune signaling. 

PMID- 24586043
TI  - Ultraviolet-B-induced stomatal closure in Arabidopsis is regulated by the UV
      RESISTANCE LOCUS8 photoreceptor in a nitric oxide-dependent mechanism.
AB  - UV RESISTANCE LOCUS8 (UVR8) signaling involves CONSTITUTIVELY PHOTOMORPHOGENIC1,
      the ELONGATED HYPOCOTYL5 (HY5) transcription factor, and the closely related HY5
      HOMOLOG. Some UV-B responses mediated by UVR8 are also regulated by nitric oxide
      (NO), a bioactive molecule that orchestrates a wide range of processes in plants.
      In this study, we investigated the participation of the UVR8 pathway and its
      interaction with NO in UV-B-induced stomatal movements in Arabidopsis
      (Arabidopsis thaliana). Stomata in abaxial epidermal strips of Arabidopsis
      ecotype Landsberg erecta closed in response to increasing UV-B fluence rates,
      with maximal closure after 3-h exposure to 5.46 MUmol m-2 s-1 UV-B. Both hydrogen
      peroxide (H2O2) and NO increased in response to UV-B, and stomatal closure was
      maintained by NO up to 24 h after the beginning of exposure. Stomata of plants
      expressing bacterial NO dioxygenase, which prevents NO accumulation, did not
      close in response to UV-B, although H2O2 still increased. When the uvr8-1 null
      mutant was exposed to UV-B, stomata remained open, irrespective of the fluence
      rate. Neither NO nor H2O2 increased in stomata of the uvr8-1 mutant. However, the
      NO donor S-nitrosoglutathione induced closure of uvr8-1 stomata to the same
      extent as in the wild type. Experiments with mutants in UVR8 signaling components
      implicated CONSTITUTIVELY PHOTOMORPHOGENIC1, HY5, and HY5 HOMOLOG in UV-B-induced
      stomatal closure. This research provides evidence that the UVR8 pathway regulates
      stomatal closure by a mechanism involving both H2O2 and NO generation in response
      to UV-B exposure.

PMID- 24586044
TI  - Arabidopsis WRKY45 transcription factor activates PHOSPHATE TRANSPORTER1;1
      expression in response to phosphate starvation.
AB  - The WRKY transcription factor family has more than 70 members in the Arabidopsis
      (Arabidopsis thaliana) genome, and some of them are involved in plant responses
      to biotic and abiotic stresses. This study evaluated the role of WRKY45 in
      regulating phosphate (Pi) uptake in Arabidopsis. WRKY45 was localized in the
      nucleus and mainly expressed in roots. During Pi starvation, WRKY45 expression
      was markedly induced, typically in roots. WRKY45 overexpression in Arabidopsis
      increased Pi content and uptake, while RNA interference suppression of WRKY45
      decreased Pi content and uptake. Furthermore, the WRKY45-overexpressing lines
      were more sensitive to arsenate, the analog of Pi, compared with wild-type
      seedlings. These results indicate that WRKY45 positively regulates Arabidopsis Pi
      uptake. Quantitative real-time polymerase chain reaction and beta-glucuronidase
      staining assays showed that PHOSPHATE TRANSPORTER1;1 (PHT1;1) expression was
      enhanced in the WRKY45-overexpressing lines and slightly repressed in the WRKY45
      RNA interference line. Chromatin immunoprecipitation and electrophoretic mobility
      shift assay results indicated that WRKY45 can bind to two W-boxes within the
      PHT1;1 promoter, confirming the role of WRKY45 in directly up-regulating PHT1;1
      expression. The pht1;1 mutant showed decreased Pi content and uptake, and
      overexpression of PHT1;1 resulted in enhanced Pi content and uptake. Furthermore,
      the PHT1;1-overexpressing line was much more sensitive to arsenate than WRKY45
      overexpressing and wild-type seedlings, indicating that PHT1;1 overexpression can
      enhance Arabidopsis Pi uptake. Moreover, the enhanced Pi uptake and the increased
      arsenate sensitivity of the WRKY45-overexpressing line was impaired by pht1;1
      (35S:WRKY45-18::pht1;1), demonstrating an epistatic genetic regulation between
      WRKY45 and PHT1;1. Together, our results demonstrate that WRKY45 is involved in
      Arabidopsis response to Pi starvation by direct up-regulation of PHT1;1
      expression.

PMID- 24586045
TI  - Efficient inference of recombination hot regions in bacterial genomes.
AB  - In eukaryotes, detailed surveys of recombination rates have shown variation at
      multiple genomic scales and the presence of "hotspots" of highly elevated
      recombination. In bacteria, studies of recombination rate variation are less
      developed, in part because there are few analysis methods that take into account
      the clonal context within which bacterial evolution occurs. Here, we focus in
      particular on identifying "hot regions" of the genome where DNA is transferred
      frequently between isolates. We present a computationally efficient algorithm
      based on the recently developed "chromosome painting" algorithm, which
      characterizes patterns of haplotype sharing across a genome. We compare the
      average genome wide painting, which principally reflects clonal descent, with the
      painting for each site which additionally reflects the specific deviations at the
      site due to recombination. Using simulated data, we show that hot regions have
      consistently higher deviations from the genome wide average than normal regions.
      We applied our approach to previously analyzed Escherichia coli genomes and
      revealed that the new method is highly correlated with the number of
      recombination events affecting each site inferred by ClonalOrigin, a method that
      is only applicable to small numbers of genomes. Furthermore, we analyzed
      recombination hot regions in Campylobacter jejuni by using 200 genomes. We
      identified three recombination hot regions, which are enriched for genes related
      to membrane proteins. Our approach and its implementation, which is downloadable
      from https://github.com/bioprojects/orderedPainting, will help to develop a new
      phase of population genomic studies of recombination in prokaryotes. 

PMID- 24586046
TI  - Differential codon adaptation between dsDNA and ssDNA phages in Escherichia coli.
AB  - Because phages use their host translation machinery, their codon usage should
      evolve toward that of highly expressed host genes. We used two indices to measure
      codon adaptation of phages to their host, rRSCU (the correlation in relative
      synonymous codon usage [RSCU] between phages and their host) and Codon Adaptation
      Index (CAI) computed with highly expressed host genes as the reference set
      (because phage translation depends on host translation machinery). These indices
      used for this purpose are appropriate only when hosts exhibit little mutation
      bias, so only phages parasitizing Escherichia coli were included in the analysis.
      For double-stranded DNA (dsDNA) phages, both r(RSCU) and CAI decrease with
      increasing number of transfer RNA genes encoded by the phage genome. r(RSCU) is
      greater for dsDNA phages than for single-stranded DNA (ssDNA) phages, and the low
      r(RSCU) values are mainly due to poor concordance in RSCU values for Y-ending
      codons between ssDNA phages and the E. coli host, consistent with the predicted
      effect of C->T mutation bias in the ssDNA phages. Strong C->T mutation bias would
      improve codon adaptation in codon families (e.g., Gly) where U-ending codons are
      favored over C-ending codons ("U-friendly" codon families) by highly expressed
      host genes but decrease codon adaptation in other codon families where highly
      expressed host genes favor C-ending codons against U-ending codons ("U-hostile"
      codon families). It is remarkable that ssDNA phages with increasing C->T mutation
      bias also increased the usage of codons in the "U-friendly" codon families,
      thereby achieving CAI values almost as large as those of dsDNA phages. This
      represents a new type of codon adaptation.

PMID- 24586047
TI  - Multiple cells-of-origin of mutant K-Ras-induced mouse lung adenocarcinoma.
AB  - Much controversy surrounds the cell-of-origin of mutant K-Ras (K-RasG12D)-induced
      lung adenocarcinoma. To shed light on this issue, we have used technology that
      enables us to conditionally target K-RasG12D expression in Surfactant Protein C
      (SPC)(+) alveolar type 2 cells and in Clara cell antigen 10 (CC10)(+) Clara cells
      by use of cell-type-restricted recombinant Adeno-Cre viruses. Experiments were
      performed both in the presence and absence of the tumor suppressor gene p53,
      enabling us to assess what effect the cell-of-origin and the introduced genetic
      lesions have on the phenotypic characteristics of the resulting adenocarcinomas.
      We conclude that both SPC-expressing alveolar type 2 cells and CC10-expressing
      Clara cells have the ability to initiate malignant transformation following the
      introduction of these genetic alterations. The lungs of K-Ras(lox-Stop-lox
      G12D/+) and K-Ras(lox-Stop-lox-G12D/+);tumor suppressor gene Trp53(F/F) mice
      infected with Adeno5-SPC-Cre and Adeno5-CC10-Cre viruses displayed differences in
      their tumor spectrum, indicating distinct cellular routes of tumor initiation.
      Moreover, using a multicolor Cre reporter line, we demonstrate that the resulting
      tumors arise from a clonal expansion of switched cells. Taken together, these
      results indicate that there are multiple cellular paths to K-RasG12D-induced
      adenocarcinoma and that the initiating cell influences the histopathological
      phenotype of the tumors that arise. 

PMID- 24586048
TI  - TGF-beta-inducible microRNA-183 silences tumor-associated natural killer cells.
AB  - Transforming growth factor beta1 (TGF-beta), enriched in the tumor
      microenvironment and broadly immunosuppressive, inhibits natural killer (NK) cell
      function by yet-unknown mechanisms. Here we show that TGF-beta-treated human NK
      cells exhibit reduced tumor cytolysis and abrogated perforin polarization to the
      immune synapse. This result was accompanied by loss of surface expression of
      activating killer Ig-like receptor 2DS4 and NKp44, despite intact cytoplasmic
      stores of these receptors. Instead, TGF-beta depleted DNAX activating protein 12
      kDa (DAP12), which is critical for surface NK receptor stabilization and
      downstream signal transduction. Mechanistic analysis revealed that TGF-beta
      induced microRNA (miR)-183 to repress DAP12 transcription/translation. This
      pathway was confirmed with luciferase reporter constructs bearing the DAP12 3'
      untranslated region as well as in human NK cells by use of sense and antisense
      miR-183. Moreover, we documented reduced DAP12 expression in tumor-associated NK
      cells in lung cancer patients, illustrating this pathway to be consistently
      perturbed in the human tumor microenvironment. 

PMID- 24586052
TI  - Sarcoidosis with ocular involvement.

PMID- 24586049
TI  - NRAS isoforms differentially affect downstream pathways, cell growth, and cell
      transformation.
AB  - Neuroblastoma rat sarcoma (RAS) viral oncogene homolog (NRAS), a small GTPase, is
      one of the most thoroughly studied oncogenes that controls cell growth,
      differentiation, and survival by facilitating signal transduction. Here, we
      identify four novel naturally occurring NRAS isoforms (isoforms 2-5) in addition
      to the canonical isoform (isoform 1). Expression analyses performed on a panel of
      several different human malignancies and matching normal tissue revealed distinct
      isoform expression patterns. Two of the novel isoforms were found in the nucleus
      and cytoplasm, whereas the others were exclusively cytoplasmic. The isoforms
      varied in their binding affinities to known downstream targets and differentially
      regulated the RAS signaling pathway. Strikingly, forced expression of isoform 5,
      which encodes only a 20-aa peptide, led to increased cell proliferation and to
      transformation by activation of known NRAS targets. These discoveries open new
      avenues in the study of NRAS. 

PMID- 24586051
TI  - High-throughput sequencing reveals inbreeding depression in a natural population.
AB  - Proxy measures of genome-wide heterozygosity based on approximately 10
      microsatellites have been used to uncover heterozygosity fitness correlations
      (HFCs) for a wealth of important fitness traits in natural populations. However,
      effect sizes are typically very small and the underlying mechanisms remain
      contentious, as a handful of markers usually provides little power to detect
      inbreeding. We therefore used restriction site associated DNA (RAD) sequencing to
      accurately estimate genome-wide heterozygosity, an approach transferrable to any
      organism. As a proof of concept, we first RAD sequenced oldfield mice (Peromyscus
      polionotus) from a known pedigree, finding strong concordance between the
      inbreeding coefficient and heterozygosity measured at 13,198 single-nucleotide
      polymorphisms (SNPs). When applied to a natural population of harbor seals (Phoca
      vitulina), a weak HFC for parasite infection based on 27 microsatellites
      strengthened considerably with 14,585 SNPs, the deviance explained by
      heterozygosity increasing almost fivefold to a remarkable 49%. These findings
      arguably provide the strongest evidence to date of an HFC being due to inbreeding
      depression in a natural population lacking a pedigree. They also suggest that
      under some circumstances heterozygosity may explain far more variation in fitness
      than previously envisaged. 

PMID- 24586053
TI  - In vitro Fab display: a cell-free system for IgG discovery.
AB  - Selection technologies such as ribosome display enable the rapid discovery of
      novel antibody fragments entirely in vitro. It has been assumed that the open
      nature of the cell-free reactions used in these technologies limits selections to
      single-chain protein fragments. We present a simple approach for the selection of
      multi-chain proteins, such as antibody Fab fragments, using ribosome display.
      Specifically, we show that a two-chain trastuzumab (Herceptin) Fab domain can be
      displayed in a format which tethers either the heavy or light chain to the
      ribosome while retaining functional antigen binding. Then, we constructed
      synthetic Fab HC and LC libraries and performed test selections against
      carcinoembryonic antigen (CEA) and vascular endothelial growth factor (VEGF). The
      Fab selection output was reformatted into full-length immunoglobulin Gs (IgGs)
      and directly expressed at high levels in an optimized cell-free system for
      immediate screening, purification and characterization. Several novel IgGs were
      identified using this cell-free platform that bind to purified CEA, CEA positive
      cells and VEGF. 

PMID- 24586054
TI  - Diverse sequences are functional at the C-terminus of the E. coli periplasmic
      chaperone SurA.
AB  - SurA is a major periplasmic molecular chaperone in Escherichia coli and has been
      shown to assist the biogenesis of several outer membrane proteins. The C-terminal
      fragment of SurA folds into a short beta-strand, which forms a small three
      stranded anti-parallel beta-sheet module with the N-terminal beta-hairpin. We
      found that the length of the C-terminal fragment, rather than its exact amino
      acid composition, had a big impact on SurA function. To investigate the
      determinant factor of the C-terminal sequence, we created a library of SurA
      constructs randomized in the last 10 residues. We screened the library and
      randomly analyzed 19 constructs that displayed SurA activity. The C-termini of
      these constructs shared little sequence similarity, except that beta-strand
      forming residues were preferentially enriched. Three SurA constructs were
      expressed and purified for structural characterization. Circular dichroism and
      fluorescence spectroscopy analyses revealed that their structures were similar to
      the structure of the wild-type SurA. Our results suggest that for scaffolding
      purpose proteins may tolerate various sequences provided certain general
      requirements such as hydrophobicity and secondary structure propensity are
      satisfied. Furthermore, the sequence tolerance of SurA at the C-terminus
      indicates that this area is not likely to be involved in substrate binding. 

PMID- 24586055
TI  - Gene expression in human ovarian tissue after xenografting.
AB  - Cryobanking and transplantation of ovarian tissue is a promising approach to
      restore fertility in cancer patients. However, ischemic stress following
      avascular ovarian cortex grafting is known to induce stromal tissue fibrosis and
      alterations in follicular development. The aim of the study was to analyze the
      impact of freeze-thawing and grafting procedures on gene expression in human
      ovarian tissue. Frozen-thawed ovarian tissue from 14 patients was xenografted for
      7 days to nude mice and one ungrafted fragment was used as a control. Immediately
      after recovery, grafts were processed for RNA extraction and histological
      analysis. Their expression profile was screened by whole-genome oligonucleotide
      array (n = 4) and validated by reverse-transcriptase polymerase chain analysis (n
      = 10). After data filtering, the Limma package was used to build a linear
      regression model for each gene and to compute its fold change between tissues on
      Days 0 and 7. After adjusting the P-value by the Sidak method, 84 of the
      transcripts were significantly altered after 7 days of grafting, including matrix
      metalloproteinase-9 and -14 and angiogenic factors such as placental growth
      factor and C-X-C chemokine receptor type 4 (CXCR4). Major biological processes
      were related to tissue remodeling, including secretory processes, cellular
      adhesion and response to chemical and hormonal stimuli. Angiopoietin signaling,
      the interleukin-8 pathway and peroxisome proliferator-activated receptor
      activation were shown to be differentially regulated. On Day 7, overexpression
      was confirmed by PCR for interleukin-8, transforming growth factor-beta 1, matrix
      metalloproteinase-14 and CXCR4, compared with ungrafted controls. In conclusion,
      new as well as known genes involved in tissue restructuring and angiogenesis were
      identified and found to play a key role during the first days after human ovarian
      tissue transplantation. This will facilitate the development of strategies to
      optimize grafting techniques. 

PMID- 24586056
TI  - Kinetics of drug interaction with the Kv11.1 potassium channel.
AB  - The Kv11.1 potassium channel is the molecular target for the majority of drugs
      implicated in acquired long QT syndrome, the most common cause of drug-induced
      sudden cardiac death, and a common reason for drug restriction or withdrawal from
      the market. While the IC50 for block of Kv11.1 is commonly used to estimate the
      risk of acquired long QT syndrome, this approach is crude, and it is widely
      accepted that the kinetics of drug interactions with the channel are a critical
      component in understanding their mechanism of action and risk profiles. In this
      study we report the first directly measured kinetics of block and unblock of
      Kv11.1 by a QT prolonging drug: the antipsychotic clozapine. Our data show that
      clozapine binding to Kv11.1 is complex. There are at least two kinetically
      distinct components to both block and unblock, while the kinetics of unblock are
      dependent on the dose or duration of drug application. Based on these
      observations, we have proposed a model incorporating kinetically distinct binding
      to the open and inactivated states of Kv11.1 that can describe the observed
      kinetic features of clozapine block and correctly predict the overall affinity
      and apparent nonstate-dependent interaction of clozapine with Kv11.1. Mechanistic
      insights into drug block of Kv11.1 gained though detailed kinetic analyses such
      as this have a potential role in development of drugs targeted to specific
      channel states to reduce unwanted side effects, as well as in the design of
      better high-throughput preclinical tests for assessing the proarrhythmic effects
      of QT prolonging drugs. 

PMID- 24586058
TI  - Reply to comments on "evaluation of dabigatran exposures reported to poison
      centers".

PMID- 24586057
TI  - Differential effects of the Gbeta5-RGS7 complex on muscarinic M3 receptor-induced
      Ca2+ influx and release.
AB  - The G protein beta subunit Gbeta5 uniquely forms heterodimers with R7 family
      regulators of G protein signaling (RGS) proteins (RGS6, RGS7, RGS9, and RGS11)
      instead of Ggamma. Although the Gbeta5-RGS7 complex attenuates Ca(2+) signaling
      mediated by the muscarinic M3 receptor (M3R), the route of Ca(2+) entry (i.e.,
      release from intracellular stores and/or influx across the plasma membrane) is
      unknown. Here, we show that, in addition to suppressing carbachol-stimulated
      Ca(2+) release, Gbeta5-RGS7 enhanced Ca(2+) influx. This novel effect of Gbeta5
      RGS7 was blocked by nifedipine and 2-aminoethoxydiphenyl borate. Experiments with
      pertussis toxin, an RGS domain-deficient mutant of RGS7, and UBO-QIC {L
      threonine,(3R)-N-acetyl-3-hydroxy-L-leucyl-(aR)-a-hydroxybenzenepropanoyl-2,3
      idehydro-N-methylalanyl-L-alanyl-N-methyl-L-alanyl-(3R)-3-[[(2S,3R)-3-hydroxy-4-
      methyl-1-oxo-2-[(1-oxopropyl)amino]pentyl]oxy]-L-leucyl-N,O-dimethyl-,(7->1)
      lactone (9CI)}, a novel inhibitor of Gq, showed that Gbeta5-RGS7 modulated a Gq
      mediated pathway. These studies indicate that Gbeta5-RGS7, independent of RGS7
      GTPase-accelerating protein activity, couples M3R to a nifedipine-sensitive
      Ca(2+) channel. We also compared the action of Gbeta5-RGS7 on M3R-induced Ca(2+)
      influx and release elicited by different muscarinic agonists. Responses to Oxo-M
      [oxotremorine methiodide N,N,N,-trimethyl-4-(2-oxo-1-pyrrolidinyl)-2-butyn-1
      ammonium iodide] were insensitive to Gbeta5-RGS7. Pilocarpine responses consisted
      of a large release and modest influx components, of which the former was strongly
      inhibited whereas the latter was insensitive to Gbeta5-RGS7. McN-A-343 [(4
      hydroxy-2-butynyl)-1-trimethylammonium-3-chlorocarbanilate chloride] was the only
      compound whose total Ca(2+) response was enhanced by Gbeta5-RGS7, attributed to,
      in part, by the relatively small Ca(2+) release this partial agonist stimulated.
      Together, these results show that distinct agonists not only have differential
      M3R functional selectivity, but also confer specific sensitivity to the Gbeta5
      RGS7 complex. 

PMID- 24586059
TI  - Longitudinal effects of medication nonadherence on glycemic control.
AB  - BACKGROUND: Medication nonadherence is known to worsen glycemic control. Few
      studies have examined this relationship over several years. OBJECTIVE: The aim of
      this study was to examine the longitudinal effect of medication nonadherence on
      glycemic control among a large cohort of veterans. METHODS: Analysis was
      performed on a cohort of 11 272 veterans with type 2 diabetes followed from April
      1994 to May 2006. The primary outcome measures were mean glycosylated hemoglobin
      A1c (A1C) and proportion in poor control (A1C > 8%) over time. The main predictor
      was medication nonadherence based on medication possession ratio (MPR). Other
      covariates included sociodemographics and ICD-9 coded medical and psychiatric
      comorbidities. Generalized linear mixed models (GLMMs) were used to assess the
      relationship between MPR and A1C after adjusting for covariates. RESULTS: Mean
      follow-up was 5.4 years. In the linear mixed model, after adjusting for baseline
      A1C and other confounding variables, mean A1C decreased by 0.24 (P < 0.001) for
      each 10% increase in MPR (95% CI = -0.27, -0.21). In the fully adjusted GLMM,
      each percentage increase in MPR was associated with a 48% lower likelihood of
      having poor glycemic control (odds ratio = 0.52; 95% CI = 0.4, 0.6). In both
      continuous and dichotomized A1C analyses, average A1C showed a decreasing trend
      over the study period (P < 0.001). CONCLUSIONS: In patients with type 2 diabetes,
      glycemic control worsens over time in the presence of medication nonadherence.
      Future studies need to take into account the complexity of patient- and system
      level factors affecting long-term medication adherence to improve diabetes
      related outcomes.

PMID- 24586060
TI  - Successful treatment of infective panniculitis with daptomycin in a pregnant,
      morbidly obese patient.
AB  - OBJECTIVE: To report a case of infective panniculitis in a morbidly obese,
      pregnant woman, which was successfully treated with daptomycin. CASE SUMMARY: A
      34-year-old, 27-week pregnant, morbidly obese woman with a history of skin/soft
      tissue infections and diabetes mellitus, presented with panniculitis. Initial
      treatment with beta-lactam antibiotics did not result in clinical improvement.
      Methicillin-resistant Staphylococcus aureus was suspected, and 14 days of
      daptomycin 4 mg/kg (using total body weight) resulted in a clinical cure, without
      any adverse effects on the mother or the neonate. DISCUSSION: Panniculitis is a
      type of skin/soft-tissue infection that is often caused by Gram-positive
      microorganisms. Daptomycin is one of the recommended agents for the treatment of
      skin/soft-tissue infections in hospitalized patients; however, it has not been
      extensively studied in pregnancy or morbid obesity. Some data suggest that
      exposure to daptomycin is significantly increased in morbidly obese persons
      because of the higher total dose received in this patient population. Animal data
      suggest that this drug is safe in pregnancy (category B), and at the time of
      publication, 3 prior cases of safe use of daptomycin in pregnancy have been
      reported. CONCLUSIONS: This case provides additional evidence for the use of
      daptomycin in pregnancy as well as morbid obesity.

PMID- 24586061
TI  - Digital cell quantification identifies global immune cell dynamics during
      influenza infection.
AB  - Hundreds of immune cell types work in coordination to maintain tissue
      homeostasis. Upon infection, dramatic changes occur with the localization,
      migration, and proliferation of the immune cells to first alert the body of the
      danger, confine it to limit spreading, and finally extinguish the threat and
      bring the tissue back to homeostasis. Since current technologies can follow the
      dynamics of only a limited number of cell types, we have yet to grasp the full
      complexity of global in vivo cell dynamics in normal developmental processes and
      disease. Here, we devise a computational method, digital cell quantification
      (DCQ), which combines genome-wide gene expression data with an immune cell
      compendium to infer in vivo changes in the quantities of 213 immune cell
      subpopulations. DCQ was applied to study global immune cell dynamics in mice
      lungs at ten time points during 7 days of flu infection. We find dramatic changes
      in quantities of 70 immune cell types, including various innate, adaptive, and
      progenitor immune cells. We focus on the previously unreported dynamics of four
      immune dendritic cell subtypes and suggest a specific role for CD103(+) CD11b(-)
      DCs in early stages of disease and CD8(+) pDC in late stages of flu infection. 

PMID- 24586062
TI  - Estimating differential expression from multiple indicators.
AB  - Regardless of the advent of high-throughput sequencing, microarrays remain
      central in current biomedical research. Conventional microarray analysis
      pipelines apply data reduction before the estimation of differential expression,
      which is likely to render the estimates susceptible to noise from signal
      summarization and reduce statistical power. We present a probe-level framework,
      which capitalizes on the high number of concurrent measurements to provide more
      robust differential expression estimates. The framework naturally extends to
      various experimental designs and target categories (e.g. transcripts, genes,
      genomic regions) as well as small sample sizes. Benchmarking in relation to
      popular microarray and RNA-sequencing data-analysis pipelines indicated high and
      stable performance on the Microarray Quality Control dataset and in a cell
      culture model of hypoxia. Experimental-data-exhibiting long-range epigenetic
      silencing of gene expression was used to demonstrate the efficacy of detecting
      differential expression of genomic regions, a level of analysis not embraced by
      conventional workflows. Finally, we designed and conducted an experiment to
      identify hypothermia-responsive genes in terms of monotonic time-response. As a
      novel insight, hypothermia-dependent up-regulation of multiple genes of two major
      antioxidant pathways was identified and verified by quantitative real-time PCR. 

PMID- 24586064
TI  - EMG rectification has inconsistent effects on coherence analysis even in single
      motor unit studies.

PMID- 24586063
TI  - Fuzziness and noise in nucleosomal architecture.
AB  - Nucleosome organization plays a key role in the regulation of gene expression.
      However, despite the striking advances in the accuracy of nucleosome maps, there
      are still severe discrepancies on individual nucleosome positioning and how this
      influences gene regulation. The variability among nucleosome maps, which
      precludes the fine analysis of nucleosome positioning, might emerge from diverse
      sources. We have carefully inspected the extrinsic factors that may induce
      diversity by the comparison of microccocal nuclease (MNase)-Seq derived
      nucleosome maps generated under distinct conditions. Furthermore, we have also
      explored the variation originated from intrinsic nucleosome dynamics by
      generating additional maps derived from cell cycle synchronized and asynchronous
      yeast cultures. Taken together, our study has enabled us to measure the effect of
      noise in nucleosome occupancy and positioning and provides insights into the
      underlying determinants. Furthermore, we present a systematic approach that may
      guide the standardization of MNase-Seq experiments in order to generate
      reproducible genome-wide nucleosome patterns. 

PMID- 24586065
TI  - Reply to McClelland et al.: EMG rectification and coherence analysis.

PMID- 24586066
TI  - Invited commentary.

PMID- 24586067
TI  - Invited commentary.

PMID- 24586068
TI  - Invited commentary.

PMID- 24586069
TI  - Invited commentary.

PMID- 24586071
TI  - Complement factor H gene associations with end-stage kidney disease in African
      Americans.
AB  - BACKGROUND: Mutations in the complement factor H gene (CFH) region associate with
      renal-limited mesangial proliferative forms of glomerulonephritis including IgA
      nephropathy (IgAN), dense deposit disease (DDD) and C3 glomerulonephritis (C3GN).
      Lack of kidney biopsies could lead to under diagnosis of CFH-associated end-stage
      kidney disease (ESKD) in African Americans (AAs), with incorrect attribution to
      other causes. A prior genome-wide association study in AAs with non-diabetic ESKD
      implicated an intronic CFH single nucleotide polymorphism (SNP). METHODS:
      Thirteen CFH SNPs (8 exonic, 2 synonymous, 2 3'UTR, and the previously associated
      intronic variant rs379489) were tested for association with common forms of non
      diabetic and type 2 diabetes-associated (T2D) ESKD in 3770 AAs (1705 with non
      diabetic ESKD, 1305 with T2D-ESKD, 760 controls). Most cases lacked kidney
      biopsies; those with known IgAN, DDD or C3GN were excluded. RESULTS: Adjusting
      for age, gender, ancestry and apolipoprotein L1 gene risk variants, single SNP
      analyses detected 6 CFH SNPs (5 exonic and the intronic variant) as significantly
      associated with non-diabetic ESKD (P = 0.002-0.01), three of these SNPs were also
      associated with T2D-ESKD. Weighted CFH locus-wide Sequence Kernel Association
      Testing (SKAT) in non-diabetic ESKD (P = 0.00053) and T2D-ESKD (P = 0.047)
      confirmed significant evidence of association. CONCLUSIONS: CFH was associated
      with commonly reported etiologies of ESKD in the AA population. These results
      suggest that a subset of cases with ESKD clinically ascribed to the effects of
      hypertension or glomerulosclerosis actually have CFH-related forms of mesangial
      proliferative glomerulonephritis. Genetic testing may prove useful to identify
      the causes of renal-limited kidney disease in patients with ESKD who lack renal
      biopsies.

PMID- 24586072
TI  - The role of SRC1 and SRC2 in steroid-induced SDF1 expression in normal and
      ectopic endometrium.
AB  - To compare the expression patterns of steroid receptor coactivators (SRCs) and
      steroid-induced stromal cell-derived factor 1 (CXCL12 (SDF1)) in normal and
      ectopic endometrium and to explore the roles of NCOA1 (SRC1) and NCOA2 (SRC2) in
      the steroid-induced CXCL12 expression in normal and ectopic endometrial stromal
      cells (ESCs). The NCOA1, NCOA2, NCOA3 (SRC3), and CXCL12 (SDF1)alpha mRNA levels
      in normal and ectopic endometrium were analyzed by quantitative real-time PCR.
      Steroid-induced CXCL12 expression was detected by the ELISA method and the
      chemotactic activity of conditioned supernatant to monocyte was assessed by the
      Boyden chamber method before and after the silencing of NCOA1 or NCOA2 with siRNA
      in normal and ectopic ESCs. The expression of NCOA1 and CXCL12 in ectopic
      endometrium was significantly greater than that in normal endometrium in the
      secretory phase. Progesterone (P4) was able to significantly inhibit estradiol
      (E2)-stimulated CXCL12 expression in normal and ectopic ESCs. The inhibitory rate
      of P4 in ectopic ESCs at 72 and 96 h was significantly lower than that in normal
      ESCs. Silencing of NCOA1 but not NCOA2 significantly reduced the E2-induced
      CXCL12 expression in normal and ectopic ESCs. The ability of P4 to inhibit E2
      induced CXCL12 expression and monocyte chemotaxis in normal and ectopic ESCs was
      significantly attenuated when NCOA2 was silenced. NCOA1 plays a necessary role in
      E2-induced CXCL12 expression and NCOA2 is required for P4 to inhibit the E2
      induced CXCL12 production in normal and ectopic endometrium.

PMID- 24586070
TI  - Prevalence of subclinical atheromatosis and associated risk factors in chronic
      kidney disease: the NEFRONA study.
AB  - BACKGROUND: The causes of the high cardiovascular mortality observed in chronic
      kidney disease (CKD) are unknown. Here, we report data on prevalence of
      subclinical atherosclerosis in the NEFRONA population and a stratified
      multivariate logistic analysis of factors associated with the presence of plaque.
      METHODS: We analysed 2445 patients with an estimated glomerular filtration rate
      (eGFR) <60 mL/min (CKD 3: 937; CKD 4-5: 820; CKD 5D: 688) and 559 non-CKD
      subjects (eGFR >60 mL/min), 18-75 years old, without previous cardiovascular
      events. An itinerant team of professionals performed carotid and femoral arterial
      ultrasound. RESULTS: The already high prevalence of plaques in CKD 3 is even
      higher in more severe CKD. Multivariate logistic analysis showed that, at any CKD
      stage, age and being male are independently associated with the presence of
      plaques. In CKD 3, there was a significant interaction of the smoking status and
      triglycerides levels which were independently associated with the presence of
      plaque. Furthermore, being diabetic was also associated with the presence of
      subclinical atherosclerosis. In stage 4-5 there was a significant association
      with smoking, high phosphate and hsCRP levels. In dialysis patients, being
      diabetic, having low levels of 25(OH)-vitamin D3 and smoking status also showed a
      significant association with the presence of plaque. Furthermore, the association
      of phosphate levels with the presence of subclinical atheromatosis showed a U
      shaped curve. CONCLUSIONS: This analysis demonstrates the magnitude of
      subclinical atheromatous disease in a large CKD population. The patient
      characteristics associated with the presence of plaque differ in every CKD stage.

PMID- 24586073
TI  - Possible roles of the cAMP-mediators EPAC and RAP1 in decidualization of rat
      uterus.
AB  - The optimal decidualization of endometrial stromal cells (ESCs) following embryo
      implantation is one of the critical steps to establish pregnancy in rodents and
      humans. This step is intricately regulated by ovarian hormones. Using in vitro
      human ESCs model, we previously showed that activation of a cAMP mediator,
      exchange protein directly activated by cAMP (EPAC), promotes ovarian steroid- or
      cAMP analog-induced decidualization. However, expressions and functions of EPAC
      and RAP1 in the uterus during pregnancy have not yet been examined. In this
      study, we found that the expression of EPAC2 and RAP1 was markedly upregulated in
      the decidual cells at the implantation sites on days 7 and 9 of pregnancy in
      rats. Furthermore, both delayed-implantation and artificial decidualization
      models showed that EPAC2 and RAP1 expression was enhanced in decidual cells.
      Significant activation of cAMP-responsive element-binding protein (CREB), a
      central transcriptional factor of cAMP signaling, was observed in decidual cells.
      These spatiotemporal expressions of protein related EPAC pathway are overlapped
      by sites with activated cAMP signaling, indicating the association of EPAC
      signaling with decidualization. Strikingly, further studies in in vitro rat
      decidualization model showed that the cAMP analog and medroxyprogesterone
      stimulated the expression of decidual markers, while knockdown of EPAC1/2 and
      RAP1 attenuated the expressions of these markers. Together, these findings
      suggest that EPAC and RAP1 are the crucial factors for endometrial
      decidualization in rat pregnancy.

PMID- 24586074
TI  - Comments on "Proton pump inhibitor-associated hypomagnesemia: what do FDA data
      tell us?".

PMID- 24586075
TI  - Response to "Proton pump inhibitor-associated hypomagnesemia: what do FDA data
      tell us?".

PMID- 24586076
TI  - The price of hope: personalized medicine in 2014.

PMID- 24586077
TI  - Safety and efficacy of FOLFOX followed by cetuximab for metastatic colorectal
      cancer with severe liver dysfunction.
AB  - Both 5-FU and oxaliplatin have been used as single agents in patients with
      colorectal cancer and severe liver dysfunction, but the combination of these
      drugs has not yet been investigated. A 67-year-old man diagnosed with colorectal
      cancer in 2008 presented in April 2011 to Appalachian Regional Healthcare Cancer
      Center with obstructive jaundice and weight loss. Imaging studies were compatible
      with a liver mass and dilatation of the intrahepatic bile ducts. A liver biopsy
      confirmed metastatic colorectal cancer. Because his total bilirubin level was
      23.1 mg/dL, a percutaneous catheter was placed in May 2011. His total bilirubin
      level decreased to 5.9 mg/dL, but then increased to 9.4 mg/dL in June 2011. He
      was started on a FOLFOX regimen, with a 50% dose reduction of 5-FU bolus (200
      mg/m(2)) and continuous infusion (1200 mg/m(2)) over 46 hours, and a 15% dose
      reduction of oxaliplatin (75 mg/m(2)) every 2 weeks. He tolerated this regimen
      very well, with normalization of his bilirubin level, a significant decrease in
      his tumor markers, and a partial response seen on PET/CT scan. His only
      significant toxicity was a grade 2 stomatitis. He received 21 cycles of FOLFOX,
      and was later switched to cetuximab treatment after disease progression. These
      findings suggest that FOLFOX might be effective in metastatic colon cancer with
      severe liver dysfunction, with minimal toxicity, and deserves further
      investigation. 

PMID- 24586078
TI  - Evolving treatment options for locally advanced unresectable pancreatic ductal
      adenocarcinoma.
AB  - The best treatment strategy for patients with locally advanced unresectable
      pancreatic ductal adenocarcinoma (PDAC) remains the subject of considerable
      debate. This report presents a case of a 58-year-old woman with locally advanced
      unresectable PDAC who was treated with sequential FOLFIRINOX for 8 cycles
      followed by chemoradiation, and continues to show durable disease control 18
      months later. The respective roles of systemic therapy and chemoradiation for
      locally advanced PDAC are discussed, including optimal sequencing of these
      modalities, recent improvements in chemotherapy, and the question of whether
      radiotherapy improves survival outcomes in this disease context. 

PMID- 24586079
TI  - Kidney cancer, version 2.2014.
AB  - These NCCN Guidelines Insights highlight treatment recommendations and updates
      specific to the management of patients with advanced non-clear cell carcinoma
      included in the 2014 version of the NCCN Clinical Practice Guidelines in Oncology
      for Kidney Cancer. 

PMID- 24586081
TI  - Phase I clinical trial of bendamustine and bevacizumab for patients with advanced
      cancer.
AB  - Bendamustine, a cytotoxic alkylating agent, has shown promising results in solid
      tumors. An investigator-initiated phase I clinical trial of the anti-vascular
      endothelial growth factor agent bevacizumab and bendamustine was conducted in
      patients with advanced cancer, because the 2 drugs have different mechanisms of
      antitumor activity and nonoverlapping toxicity. Patients were treated with
      escalating doses of intravenous bendamustine (70, 80, 90, and 100 mg/m(2); days 1
      and 2) and intravenous bevacizumab (10 mg/kg; days 1 and 15). A conventional "3 +
      3" study design was used. Forty-two patients were treated: 23 women and 19 men.
      The median age was 60 years. Patients had received a median of 4 prior therapies
      (range, 1-10). The most common cancer types were colorectal (n=9), head and neck
      (n= 8), non-small cell lung (n=6), and breast (n=5). Overall, 117 cycles were
      administered (median per patient, 2; range, 1-8). No dose-limiting toxicities
      were noted during the escalation phase. Therefore, the highest dose (level 4) of
      bendamustine (100 mg/m(2)) was used in the expansion phase. The most common
      toxicities were fatigue (n=22), nausea (n=14), anorexia (n=9), and
      thrombocytopenia (n=7). Of 38 patients who were evaluable for response, 23 (61%)
      had stable disease, including 2 (5.2%) who had stable disease for 6 months or
      more (1 with adenoid cystic carcinoma and 1 with non-small cell lung cancer).
      This regimen of bendamustine (100 mg/m(2)) and bevacizumab (10 mg/kg) was well
      tolerated and yielded disease stabilization in selected heavily pretreated
      patients with advanced cancer. 

PMID- 24586080
TI  - Survivorship: sexual dysfunction (female), version 1.2013.
AB  - Cancer treatment, especially hormonal therapy and therapy directed toward the
      pelvis, can contribute to sexual problems, as can depression and anxiety, which
      are common in cancer survivors. Thus, sexual dysfunction is common in survivors
      and can cause increased distress and have a significant negative impact on
      quality of life. This section of the NCCN Guidelines for Survivorship provides
      screening, evaluation, and treatment recommendations for female sexual problems,
      including those related to sexual desire, arousal, orgasm, and pain. 

PMID- 24586082
TI  - Attitudes toward and use of cancer management guidelines in a national sample of
      medical oncologists and surgeons.
AB  - Physician attitudes toward and lack of familiarity with guidelines have been
      identified as potential barriers to adherence in general, but little is known
      about their attitudes toward and use of cancer management guidelines
      specifically. This study surveyed 1500 surgeons and medical oncologists drawn
      from the AMA Masterfile in 2012. This report describes and compares the attitudes
      of medical oncologists and surgeons who treat patients with breast cancer
      regarding guidelines in general and the NCCN Clinical Practice Guidelines in
      Oncology (NCCN Guidelines) in particular, and their familiarity, use, and
      compliance with these guidelines. Of 896 respondents, responses were analyzed
      from the 766 who had seen at least one new patient with breast cancer in the past
      year. Mean participant age was 52 years; 25% worked in a teaching setting.
      Attitudes toward guidelines were generally favorable. Medical oncologists were
      more likely than surgeons to be aware that NCCN issues guidelines for cancer
      management (100% vs 74%; P<.001) and more likely to state that these guidelines
      generally influence their decisions (96% vs 70%; P<.001). Among those aware of
      NCCN Guidelines, 96% reported that they often agreed with NCCN recommendations,
      and 75% reported that almost all of their breast cancer treatment recommendations
      were consistent with these guidelines. Still, most providers (77%) also reported
      that they refer one-fourth or fewer of their patients with breast cancer to the
      NCCN Guidelines for Patients. Attitudes toward physician-directed cancer
      management guidelines are generally positive, and they are frequently used.
      However, existing guidelines seem to have greater visibility to the medical
      oncology audience than to surgeons, and patient versions are infrequently
      recommended. 

PMID- 24586083
TI  - Molecular characterization of bone tumors and implications for treatment and
      prognosis.
AB  - Neoplastic transformation is a consequence of maladaptive alterations in the
      cellular processes normally involved in cell growth, proliferation,
      differentiation, and survival. Despite the relative infrequent nature of skeletal
      neoplasms, current understanding of the pathobiology underlying these conditions
      is becoming increasingly characterized. This article highlights some of the
      established molecular abnormalities identified in various benign and malignant
      skeletal neoplasms and how they pertain to tumor biology, diagnosis, and
      prognosis. Most of the commonly accepted cellular aberrancies in skeletal
      neoplasms pertain to mutations, copy number changes, and/or chromosomal
      rearrangements. However, it is becoming increasingly understood that the
      complexity of tumorigenic pathways necessary for neoplastic growth are
      manipulated by numerous overlapping alterations in the genetic code and are
      further influenced by higher-order molecular programs, such as pretranscriptional
      and posttranscriptional regulation and chromatin reorganization. Over time,
      identification and quantification of these increasingly recognized neoplastic
      processes will gradually translate into valuable clinical applications, enhancing
      the current diagnostic and prognostic capabilities. 

PMID- 24586084
TI  - The international endorsement of US distress screening and psychosocial
      guidelines in oncology: a model for dissemination.
AB  - The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Distress
      Management have, since 1997, called for routine screening of distress in patients
      with cancer. Following the example of pain as the fifth vital sign, the case for
      using the concept of distress as the sixth vital sign was made by leading psycho
      oncologists in 2007. Cancer care organizations in Canada and the International
      Psycho-Oncology Society have adopted the NCCN Guidelines for Distress Management
      and have named distress screening as the sixth vital sign, thereby encouraging
      cancer care clinicians to think of screening for distress when they screen for
      pain and other vital signs. Using the evidence integration triangle, this article
      explores the dissemination of the notion of distress as the sixth vital sign in
      an international context. This exploration shows that NCCN and similar
      organizations can adopt the evidence integration triangle in its next phase of
      moving toward full implementation of the NCCN Guidelines for Distress Management.

PMID- 24586085
TI  - Neoadjuvant radiotherapy use in locally advanced rectal cancer at NCCN member
      institutions.
AB  - Based on randomized data, neoadjuvant chemoradiotherapy has been incorporated
      into the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for
      stage II-III rectal cancer. Factors associated with nonadherence to evidence
      based guidelines for neoadjuvant radiotherapy (RT) were examined at dedicated
      cancer centers. The prospective NCCN Oncology Outcomes Database for Colorectal
      Cancers was queried for patients with stage II-III rectal cancer who underwent a
      transabdominal surgical resection between September 2005 and June 2012.
      Multivariable logistic regression was used to identify factors associated with
      omission of RT. Among 1199 identified patients, 1119 (93%) received neoadjuvant
      RT, 51 (4%) did not receive RT, and 29 (2%) received adjuvant RT. Among 51
      patients not receiving RT, only 19 (37%) were referred and evaluated by a
      radiation oncologist. On multivariable analysis, clinical factors associated with
      not receiving RT included a history of prior pelvic RT (adjusted odds ratio
      [aOR], 23.9; P=.0003), ECOG performance status of 2 or greater (aOR, 11.1;
      P=.01), tumor distance from the anal verge greater than 10 cm (aOR, 5.4; P=.009),
      age at diagnosis of 75 years or older (aOR, 4.43; P=.002), body mass index of 25
      to 30 kg/m(2) and less than 25 kg/m(2) (aOR, 5.22 and 4.23, respectively; P=.03),
      and clinical stage II (aOR, 2.27; P=.02). No significant change was seen in RT
      use according to diagnosis year, nor was any correlation seen with distance to
      the nearest RT facility. Concordance with NCCN Guidelines for neoadjuvant RT is
      high among NCCN Member Institutions. After adjusting for clinical characteristics
      that increase the risk for RT toxicity, including history of pelvic RT and high
      comorbidity burden/low functional status, the authors found that non-obese
      patients of advanced age or those with more favorable clinical features were more
      likely to not receive RT. 

PMID- 24586086
TI  - Uterine neoplasms, version 1.2014.
AB  - Adenocarcinoma of the endometrium (also known as endometrial cancer or more
      broadly as uterine cancer or carcinoma of the uterine corpus) is the most common
      malignancy of the female genital tract in the United States. An estimated 49,560
      new uterine cancer cases will occur in 2013, with 8190 deaths resulting from the
      disease. Uterine sarcomas (stromal/mesenchymal tumors) are uncommon malignancies,
      accounting for approximately 3% of all uterine cancers. The NCCN Guidelines for
      Uterine Neoplasms describe malignant epithelial carcinomas and uterine sarcomas;
      each of these major categories contains specific histologic groups that require
      different management. This excerpt of these guidelines focuses on early-stage
      disease. 

PMID- 24586088
TI  - Moving forward with expanding to an "all-RAS mutational analysis" in metastatic
      colorectal cancer: beyond KRAS mutations.

PMID- 24586087
TI  - Sentinel lymph node mapping for endometrial cancer: a modern approach to surgical
      staging.
AB  - Most patients with endometrial cancer will present with early-stage disease.
      Although the rate of metastasis in these patients is low, proffering excellent
      prognoses, the standard of treatment in many practices still includes a complete
      or selective pelvic and para-aortic lymphadenectomy for staging; and accurate
      surgical staging is the most important prognostic factor. Many patients will
      undergo a comprehensive lymphadenectomy despite having disease confined to the
      uterus, resulting in prolonged operating time, additional cost, and potential
      side effects, such as lower extremity lymphedema. However, recent studies show
      that a complete lymphadenectomy may have no therapeutic benefit in patients with
      early-stage endometrial cancer. Sentinel lymph node (SLN) mapping, which has been
      used in other cancer types, may be an acceptable surgical strategy between a
      complete lymphadenectomy and no nodal evaluation in patients with endometrial
      cancer. SLN mapping is based on the concept that lymph node metastasis is the
      result of an orderly process; that is, lymph drains in a specific pattern away
      from the tumor, and therefore, if the SLN, or first node, is negative for
      metastasis, then the nodes after the SLN should also be negative. This approach
      can help patients avoid the side effects associated with a complete
      lymphadenectomy, although disease must be thoroughly staged for accurate
      prognosis and determination of appropriate treatment approach. Surgeon
      experience, adherence to an SLN algorithm, and the use of pathologic
      "ultrastaging" are key factors for successful SLN mapping. 

PMID- 24586091
TI  - Cross-measure equivalence and communicability in the assessment of depression: a
      focus on factor-based scales.
AB  - All measures of depression yield a global summary scale indicating the severity
      of depressive symptoms, implicitly conceptualized as a homogeneous construct.
      However, depression is a heterogeneous construct, with different presentations,
      subtypes, correlates, and responses to interventions. In response, the National
      Institute of Mental Health (NIMH) has suggested changes in the way depression is
      assessed, moving the focus to specific factors, such as cognitive, somatic, or
      affective symptoms. Still, there is little factor overlap between measures, and
      shared factors are weighted differently. To help fulfill NIMH's strategic plan,
      this study used canonical correlation analysis (CCA) to explore shared latent
      variables and redundancy across the measures. It also analyzed the psychometric
      properties of factor-based subscales in the Beck Depression Inventory-2nd edition
      (BDI-II), Center for Epidemiologic Studies Depression scale (CES-D), Inventory
      for Depression and Anxiety Symptoms (IDAS), and Inventory of Depressive
      Symptomatology (IDS). Using a diverse sample of 218 students who reported at
      least mild depressive symptoms, this study found that the IDAS was best aligned
      with NIMH's strategic plan; it has complete DSM-IV/DSM-5 symptom coverage and
      content-valid, psychometrically sound subscales. The BDI-II, CES-D, and IDS did
      not have consistent subscales, nor had incomplete or incongruent coverage of DSM
      criteria. Furthermore, CCA revealed low redundancy across measures (23% to 41%
      shared variance). These results suggest that different measures of depression do
      not measure the same construct. As a partial solution, empirical conversion
      tables were provided for researchers and clinicians to empirically compare total
      scores from different measures. 

PMID- 24586090
TI  - Examining the factor structure of the Connor-Davidson Resilience Scale (CD-RISC)
      in a post-9/11 U.S. military veteran sample.
AB  - The present study examined the structural validity of the 25-item Connor-Davidson
      Resilience Scale (CD-RISC) in a large sample of U.S. veterans with military
      service since September 11, 2001. Participants (N = 1,981) completed the 25-item
      CD-RISC, a structured clinical interview and a self-report questionnaire
      assessing psychiatric symptoms. The study sample was randomly divided into two
      subsamples: an initial sample (Sample 1: n = 990) and a replication sample
      (Sample 2: n = 991). Findings derived from exploratory factor analysis (EFA) did
      not support the five-factor analytic structure as initially suggested in Connor
      and Davidson's instrument validation study. Although parallel analyses indicated
      a two-factor structural model, we tested one to six factor solutions for best
      model fit using confirmatory factor analysis. Results supported a two-factor
      model of resilience, composed of adaptability- (8 items) and self-efficacy-themed
      (6 items) items; however, only the adaptability-themed factor was found to be
      consistent with our view of resilience-a factor of protection against the
      development of psychopathology following trauma exposure. The adaptability-themed
      factor may be a useful measure of resilience for post-9/11 U.S. military
      veterans.

PMID- 24586092
TI  - RE: Adding epoetin alfa to intense dose-dense adjuvant chemotherapy for breast
      cancer: randomized clinical trial.

PMID- 24586093
TI  - Response.

PMID- 24586094
TI  - The paradox of dementia: Changes in assimilation after receiving a diagnosis of
      dementia.
AB  - This qualitative study used semi-structured interviews to explore how six people
      talked about their difficulties before and after a dementia diagnosis.
      Participants' accounts of their memory problems were analysed in terms of the
      verbal Markers of Assimilation of Problematic Voices Scale. This analysis
      indicated that after diagnosis some participants were able to integrate aspects
      of their illness that had previously been too painful, and which had been warded
      off. The process by which individuals were able to integrate a dementia diagnosis
      into their sense of self-involved stepping in and out of awareness, with both
      acceptance and denial featuring in their accounts as they approached and then
      retreated from addressing the diagnosis. In contrast, other participants resisted
      moving towards explicitly acknowledging their dementia but were instead able to
      express concerns about what this movement would entail, for instance voicing
      their fears that it would mean that they had surrendered. Social support seems to
      have been crucial in enabling participants to sustain a positive sense of self in
      the face of this adjustment. 

PMID- 24586095
TI  - Polychlorinated dibenzo-p-dioxins, furans, and biphenyls (PCDDs/PCDFs and PCBs)
      in breast milk and early childhood growth and IGF1.
AB  - Experimental studies have shown that dioxin-like chemicals may interfere with
      aspects of the endocrine system including growth. However, human background
      population studies are, however, scarce. We aimed to investigate whether early
      exposure of healthy infants to dioxin-like chemicals was associated with changes
      in early childhood growth and serum IGF1. In 418 maternal breast milk samples of
      Danish children (born 1997-2001) from a longitudinal cohort, we measured
      polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans, and
      polychlorinated biphenyls (pg or ng/g lipid) and calculated total toxic
      equivalent (total TEQ). SDS and SDS changes over time (DeltaSDS) were calculated
      for height, weight, BMI, and skinfold fat percentage at 0, 3, 18, and 36 months
      of age. Serum IGF1 was measured at 3 months. We adjusted for confounders using
      multivariate regression analysis. Estimates (in parentheses) correspond to a
      fivefold increase in total TEQ. TEQ levels in breast milk increased significantly
      with maternal age and fish consumption and decreased with maternal birth year,
      parity, and smoking. Total TEQ was associated with lower fat percentage (-0.45
      s.d., CI: -0.89; -0.04), non-significantly with lower weight and length at 0
      months, accelerated early height growth (increased DeltaSDS) (DeltaSDS 0-18
      months: +0.77 s.d., CI: 0.34; 1.19) and early weight increase (DeltaSDS 0-18:
      +0.52 s.d., CI: 0.03; 1.00), and increased IGF1 serum levels at 3 months (+13.9
      ng/ml, CI: 2.3; 25.5). Environmental exposure to dioxin-like chemicals was
      associated with being skinny at birth and with higher infant levels of
      circulating IGF1 as well as accelerated early childhood growth (rapid catch-up
      growth). 

PMID- 24586096
TI  - D-limonene suppresses doxorubicin-induced oxidative stress and inflammation via
      repression of COX-2, iNOS, and NFkappaB in kidneys of Wistar rats.
AB  - D-limonene is a naturally occurring monoterpene and has been found to posses
      numerous therapeutic properties. In this study, we used D-limonene as a
      protective agent against the nephrotoxic effects of anticancer drug doxorubicin
      (Dox). Rats were given D-limonene at doses of 5% and 10% mixed with diet for 20
      consecutive days. Dox was give at the dose of 20 mg/kg body weight
      intraperitoneally. The protective effects of D-limonene on Dox-induced oxidative
      stress and inflammation were investigated by assaying oxidative stress
      biomarkers, lipid peroxidation, serum toxicity markers, proinflammatory
      cytokines, and expression of nuclear factor kappa B (NFkappaB), cyclo-oxygenase-2
      (COX-2), and inducible nitric oxide synthase (iNOS) and Nitrite levels.
      Administration of Dox (20 mg/kg body weight) in rats enhanced renal lipid
      peroxidation; depleted glutathione content and anti-oxidant enzymes; elevated
      levels of kidney toxicity markers viz. kidney injury molecule-1 (KIM-1), blood
      urea nitrogen (BUN), and creatinine; enhanced expression of NFkappaB, COX-2, and
      iNOS and nitric oxide. Treatment with D-limonene prevented oxidative stress by
      restoring the levels of antioxidant enzymes, further both doses of 5% and 10%
      showed significant decrease in inflammatory response. Both the doses of D
      limonene significantly decreased the levels of kidney toxicity markers KIM-1,
      BUN, and creatinine. D-limonene also effectively decreased the Dox induced
      overexpression of NF-kappaB, COX-2, and iNOS and nitric oxide. Data from the
      present study indicate the protective role of D-limonene against Dox-induced
      renal damage.

PMID- 24586097
TI  - Infliximab attenuates inflammatory osteolysis in a model of periodontitis in
      Wistar rats.
AB  - Periodontitis is a chronic inflammatory disease related to tooth loss in adults.
      Infliximab is a chimeric monoclonal antibody against TNF-alpha and is prescribed
      for the treatment of systemic inflammatory diseases. This study aimed to
      investigate the role of infliximab on experimental periodontal disease (EPD). EPD
      was induced by passing a 3.0 nylon thread around the upper left second molar in
      Wistar rats. Animals were either treated with intravenous infliximab (1, 5, 7,
      and 10 mg/kg) or saline solution 30 min before the periodontitis induction and
      were followed until they were sacrificed on the 11th day. A subset of rats was
      euthanized on the third day for analysis of gingival myeloperoxidase (MPO) and
      the blood MPO granulocyte index. In addition, we analyzed the bone loss index
      (BLI), the periodontal histopathological score, and the periodontal collagen
      network using confocal microscopy. We also analyzed metalloproteinase-1/-8, RANK,
      RANK-L, and osteoprotegerin in maxillary tissue by immunohistochemistry Gingival
      MPO, IL-1beta, TNF-alpha were measured by ELISA. EPD caused leukocytosis,
      significant increases in BLI and gingival pro-inflammatory cytokines and cell
      infiltrates, with worse histopathological scores and periodontal collagen
      derangement. Infliximab (5 mg/kg) reduced granulocyte blood counts, gingival IL
      1beta, TNF-alpha, and MPO levels, diminished MMP-1/-8, RANK, and RANK-L bone
      immunolabeling with better periodontal histopathological scores and collagen
      network in comparison with the challenged saline group. We concluded that
      infliximab had significant anti-inflammatory and bone-protective effects in
      Wistar rats challenged by periodontitis.

PMID- 24586098
TI  - Soy isoflavone affects the autonomic nervous system in a tissue-specific manner
      in anesthetized rats.
AB  - We examined and compared the effects of taste stimulation by soy saponin as well
      as soy isoflavone and intragastric (IG) injection of both on the autonomic nerve
      activities and feeding behavior in rats. We found that taste stimulation by soy
      saponin or soy isoflavone-rich solution (SIRS) did not affect the activity of the
      sympathetic nerve supplying the adrenal gland in urethane-anesthetized rats;
      however, IG injection of SIRS, but not soy saponin, stimulated the adrenal
      sympathetic nerve activity (ASNA) in a dose-dependent manner. Moreover, IG
      injection of SIRS significantly suppressed the activity of the vagus nerve
      innervating the stomach, whereas sympathetic nerve outflows to brown or white
      adipose tissue were not affected by IG injection of SIRS. To test the involvement
      of the afferent autonomic nerve in the abdominal organs for regulation of the
      efferent ASNA by SIRS, we examined the response of the adrenal sympathetic
      innervation to SIRS injection in rats with ablated afferent vagus or afferent
      sympathetic nerves. The activating effect of SIRS on the ASNA was inhibited in
      sympathectomized rats but not in vagotomized rats. Thus, our data suggest that
      soy isoflavone might affect tissue-specific autonomic nerves through the afferent
      sympathetic nerve pathway.

PMID- 24586099
TI  - Exenatide protects against hypoxia/reoxygenation-induced apoptosis by improving
      mitochondrial function in H9c2 cells.
AB  - Glucagon-like peptide-1 (GLP-1) analogues might exert the cardioprotective
      effects via attenuating apoptosis. This study aimed to determine the protective
      effects and mechanism of exenatide, a GLP-1 analogue, on cardiomyocyte apoptosis
      using an in vitro model of hypoxia/reoxygenation (H/R). H9c2 cells were employed
      to establish an in vitro model of H/R. 200 nM exenatide pretreatment
      significantly reduced apoptosis measured by flow cytometry. To further study the
      antiapoptotic mechanism of exenatide, we used flow cytometry in combination with
      laser confocal microscopy to determine the interaction between exenatide and the
      process of mitochondria-mediated apoptosis. We found that exenatide pretreatment
      reduced the intracellular reactive oxygen species (ROS) levels and decreased the
      mitochondrial calcium overload caused by H/R. Furthermore, an increase of total
      superoxide dismutase (T-SOD) levels, a decrease of malondialdehyde (MDA) levels,
      a preservation of mitochondrial membrane potential (DeltaPsim), a reduction of
      cytochrome-c release, a decline of cleaved caspase-3 expression, and caspase-3
      activation were observed in exenatide-pretreated cultures. These results suggest
      that exenatide exerts a protective effect on preventing against H/R-induced
      apoptosis. Importantly, the protective effects of exenatide may be attributed to
      its role in improving mitochondrial function in H9c2 cells subjected to H/R.

PMID- 24586101
TI  - RE: Mortality after radical prostatectomy or external beam radiotherapy for
      localized prostate cancer.

PMID- 24586102
TI  - RE: Mortality after radical prostatectomy or external beam radiotherapy for
      localized prostate cancer.

PMID- 24586100
TI  - Inhibition of glutathione synthesis distinctly alters mitochondrial and cytosolic
      redox poise.
AB  - The glutathione couple GSH/GSSG is the most abundant cellular redox buffer and is
      not at equilibrium among intracellular compartments. Perturbation of glutathione
      poise has been associated with tumorigenesis; however, due to analytical
      limitations, the underlying mechanisms behind this relationship are poorly
      understood. In this regard, we have implemented a ratiometric, genetically
      encoded redox-sensitive green fluorescent protein fused to human glutaredoxin
      (Grx1-roGFP2) to monitor real-time glutathione redox potentials in the cytosol
      and mitochondrial matrix of tumorigenic and non-tumorigenic cells. First, we
      demonstrated that recovery time in both compartments depended upon the length of
      exposure to oxidative challenge with diamide, a thiol-oxidizing agent. We then
      monitored changes in glutathione poise in cytosolic and mitochondrial matrices
      following inhibition of glutathione (GSH) synthesis with L-buthionine
      sulphoximine (BSO). The mitochondrial matrix showed higher oxidation in the BSO
      treated cells indicating distinct compartmental alterations in redox poise.
      Finally, the contributory role of the p53 protein in supporting cytosolic redox
      poise was demonstrated. Inactivation of the p53 pathway by expression of a
      dominant-negative p53 protein sensitized the cytosol to oxidation in BSO-treated
      tumor cells. As a result, both compartments of PF161-T+p53(DD) cells were equally
      oxidized ~20 mV by inhibition of GSH synthesis. Conversely, mitochondrial
      oxidation was independent of p53 status in GSH-deficient tumor cells. Taken
      together, these findings indicate different redox requirements for the
      glutathione thiol/disulfide redox couple within the cytosol and mitochondria of
      resting cells and reveal distinct regulation of their redox poise in response to
      inhibition of glutathione biosynthesis.

PMID- 24586103
TI  - Response.

PMID- 24586104
TI  - Response.

PMID- 24586105
TI  - Re: Serum miR-21 as a diagnostic and prognostic biomarker in colorectal cancer.

PMID- 24586106
TI  - New role for the mitochondrial peptide humanin: protective agent against
      chemotherapy-induced side effects.

PMID- 24586107
TI  - Protective role of humanin on bortezomib-induced bone growth impairment in
      anticancer treatment.
AB  - BACKGROUND: Bortezomib is a proteasome inhibitor currently studied in clinical
      trials of childhood cancers. So far, no side effects on bone growth have been
      reported in treated children. However, bortezomib was recently found to induce
      apoptosis in growth plate chondrocytes and impair linear bone growth in treated
      mice. We hypothesize that [Gly(14)]-humanin (HNG), a 24-amino acid synthetic
      antiapoptotic peptide, can prevent bortezomib-induced bone growth impairment.
      METHODS: Mice with human neuroblastoma or medulloblastoma tumor xenografts (9-13
      animals/group) received one 2-week cycle (2 injections/week) of bortezomib (0.8
      mg/kg or 1.0mg/kg), or HNG (1 ug/mouse), or the combination of HNG/bortezomib, or
      vehicle. Cultures of human growth plate cartilage, chondrogenic- and cancer cell
      lines, and immunohistochemistry for detection of proapoptotic proteins were also
      used. Statistical significance was evaluated by two-sided Mann-Whitney U test or
      by parametric or nonparametric analysis of variance. RESULTS: Bortezomib
      efficiently blocked the proteasome and induced pronounced impairment of linear
      bone growth from day 0 to day 13 (0.09 mm/day, 95% confidence interval [CI] =
      0.07 to 0.11 mm/day; vs 0.19 mm/day, 95% CI = 0.15 to 0.23 mm/day in vehicle; P <
      .001), an effect significantly prevented by the addition of HNG (0.15 mm
      growth/day, 95% CI = 0.14 to 0.16 mm/day; P < .001 vs bortezomib only; P = 0.03
      vs vehicle). Bortezomib was highly toxic when added to cultures of human growth
      plate cartilage, with markedly increased apoptosis compared with control (P <
      .001). However, when combining with HNG, bortezomib-induced apoptosis was
      entirely prevented, as was Bax and PARP activation. Bortezomib delayed tumor
      growth, and HNG did not interfere with the anticancer effect when studied in
      human tumor xenografts or cell lines. CONCLUSIONS: HNG prevents bortezomib
      induced bone growth impairment without interfering with bortezomib's desired
      anticancer effects.

PMID- 24586108
TI  - Epileptiform Discharges and Frontal Paroxysmal EEG Abnormality Act as Predictive
      Marker for Subsequent Epilepsy in Children With Complex Febrile Seizures.
AB  - Using electroencephalography (EEG) for diagnosing subsequent epilepsy in children
      after febrile seizure (FS) is not common. The present study investigates the
      relationship between epileptiform discharges and subsequent epilepsy, and looks
      for the predictive marker for this disorder. A total of 378 children with complex
      FS and whose EEG showed epileptiform discharges or normal EEG were included.
      Development of FS was compared between those with epileptiform discharges and
      those with normal EEG. Risk factors were analyzed using multivariate logistic
      regression to clarify their effects on subsequent epilepsy. The association
      between generalized or focal EEG localization, and between frontal epileptiform
      discharges and subsequent epilepsy, were analyzed. Among 378 patients with
      complex FS, 51 showed epileptiform discharges. History of epilepsy, frontal
      seizure, number of FS, and prolonged seizure were the risk factors for
      epileptiform discharge. Subsequent epilepsy was significantly frequent in
      patients with more than 2 risk factors (odds ratio [OR] = 17; 95% confidence
      interval [CI] = 4.1-29.6). Prolonged seizure (OR = 4.98; 95% CI = 1.63-13.29), FS
      number (OR = 2.96; 95% CI = 1.23-10.51), and family history of epilepsy (OR =
      2.67; 95% CI = 1.05-7.63) were significantly correlated with subsequent epilepsy.
      Of 9 patients with paroxysms in the frontal region, 8 (88.9%) developed epilepsy.
      There was concordance between frontal epileptiform discharges and subsequent
      epilepsy (kappa = .901). In conclusion, epileptiform discharges are risk factors
      for subsequent epilepsy. Frontal paroxysmal EEG is a marker for subsequent
      epilepsy.

PMID- 24586109
TI  - The reliability and validity of the diabetes care profile for Chinese
      populations.
AB  - This study aimed to translate into Chinese the Diabetes Care Profile (DCP), a
      measure of psychosocial factors and diabetes treatment, and to test the
      reliability and validity of the instrument within a Chinese population. The
      English version of the DCP was translated into Chinese following the standard
      translation methodology with consideration to cultural adaptation. The
      questionnaire was administered to 313 people with type 2 diabetes in an urban
      community in Beijing, China. Cronbach's alpha coefficient was used to calculate
      reliabilities, which ranged from .55 to .86 on DCP subscales. Mean values on the
      DCP differed by diabetes treatment as expected and supports the construct
      validity of the DCP. The overall score on the DCP correlated well both with blood
      glucose levels and with a validated measure of a Chinese version of the Diabetes
      Specific Quality of Life scale, thus supporting the DCP's criterion validity. The
      DCP is an acceptable measure of the psychosocial factors related to diabetes and
      its treatment in a Chinese population with type 2 diabetes. 

PMID- 24586110
TI  - Spire and Formin 2 synergize and antagonize in regulating actin assembly in
      meiosis by a ping-pong mechanism.
AB  - In mammalian oocytes, three actin binding proteins, Formin 2 (Fmn2), Spire, and
      profilin, synergistically organize a dynamic cytoplasmic actin meshwork that
      mediates translocation of the spindle toward the cortex and is required for
      successful fertilization. Here we characterize Fmn2 and elucidate the molecular
      mechanism for this synergy, using bulk solution and individual filament kinetic
      measurements of actin assembly dynamics. We show that by capping filament barbed
      ends, Spire recruits Fmn2 and facilitates its association with barbed ends,
      followed by rapid processive assembly and release of Spire. In the presence of
      actin, profilin, Spire, and Fmn2, filaments display alternating phases of rapid
      processive assembly and arrested growth, driven by a "ping-pong" mechanism, in
      which Spire and Fmn2 alternately kick off each other from the barbed ends. The
      results are validated by the effects of injection of Spire, Fmn2, and their
      interacting moieties in mouse oocytes. This original mechanism of regulation of a
      Rho-GTPase-independent formin, recruited by Spire at Rab11a-positive vesicles,
      supports a model for modulation of a dynamic actin-vesicle meshwork in the oocyte
      at the origin of asymmetric positioning of the meiotic spindle. 

PMID- 24586111
TI  - Ping-pong positioning: alternating protein interactions at actin filament barbed
      ends helps establish polarity in mammalian oocytes.

PMID- 24586113
TI  - Experience-dependent rewiring of specific inhibitory connections in adult
      neocortex.
AB  - Although neocortical connectivity is remarkably stereotyped, the abundance of
      some wiring motifs varies greatly between cortical areas. To examine if regional
      wiring differences represent functional adaptations, we have used optogenetic
      raster stimulation to map the laminar distribution of GABAergic interneurons
      providing inhibition to pyramidal cells in layer 2/3 (L2/3) of adult mouse barrel
      cortex during sensory deprivation and recovery. Whisker trimming caused large,
      motif-specific changes in inhibitory synaptic connectivity: ascending inhibition
      from deep layers 4 and 5 was attenuated to 20%-45% of baseline, whereas
      inhibition from superficial layers remained stable (L2/3) or increased moderately
      (L1). The principal mechanism of deprivation-induced plasticity was motif
      specific changes in inhibitory-to-excitatory connection probabilities; the
      strengths of extant connections were left unaltered. Whisker regrowth restored
      the original balance of inhibition from deep and superficial layers. Targeted,
      reversible modifications of specific inhibitory wiring motifs thus contribute to
      the adaptive remodeling of cortical circuits. 

PMID- 24586114
TI  - Developmental programming mediated by complementary roles of imprinted Grb10 in
      mother and pup.
AB  - Developmental programming links growth in early life with health status in
      adulthood. Although environmental factors such as maternal diet can influence the
      growth and adult health status of offspring, the genetic influences on this
      process are poorly understood. Using the mouse as a model, we identify the
      imprinted gene Grb10 as a mediator of nutrient supply and demand in the postnatal
      period. The combined actions of Grb10 expressed in the mother, controlling
      supply, and Grb10 expressed in the offspring, controlling demand, jointly
      regulate offspring growth. Furthermore, Grb10 determines the proportions of lean
      and fat tissue during development, thereby influencing energy homeostasis in the
      adult. Most strikingly, we show that the development of normal lean/fat
      proportions depends on the combined effects of Grb10 expressed in the mother,
      which has the greater effect on offspring adiposity, and Grb10 expressed in the
      offspring, which influences lean mass. These distinct functions of Grb10 in
      mother and pup act complementarily, which is consistent with a coadaptation model
      of imprinting evolution, a model predicted but for which there is limited
      experimental evidence. In addition, our findings identify Grb10 as a key genetic
      component of developmental programming, and highlight the need for a better
      understanding of mother-offspring interactions at the genetic level in predicting
      adult disease risk. 

PMID- 24586115
TI  - Genomic imprinting of Grb10: coadaptation or conflict?
AB  - Mammalian development involves significant interactions between offspring and
      mother. But is this interaction a carefully coordinated effort by two individuals
      with a common goal--offspring survival? Or is it an evolutionary battleground (a
      central idea in our understanding of reproduction). The conflict between parents
      and offspring extends to an offspring's genes, where paternally inherited genes
      favor demanding more from the mother, while maternally inherited genes favor
      restraint. This "intragenomic conflict" (among genes within a genome) is the
      dominant evolutionary explanation for "genomic imprinting." But a new study in
      PLOS Biology provides support for a different perspective: that imprinting might
      facilitate coordination between mother and offspring. According to this
      "coadaptation theory," paternally inherited genes might be inactivated because
      maternally inherited genes are adapted to function harmoniously with the mother.
      As discussed in this article, the growth effects associated with the imprinted
      gene Grb10 are consistent with this idea, but it remains to be seen just how
      general the pattern is.

PMID- 24586116
TI  - How do filamentous pathogens deliver effector proteins into plant cells?
AB  - Fungal and oomycete plant parasites are among the most devastating pathogens of
      food crops. These microbes secrete effector proteins inside plant cells to
      manipulate host processes and facilitate colonization. How these effectors reach
      the host cytoplasm remains an unclear and debated area of plant research. In this
      article, we examine recent conflicting findings that have generated discussion in
      the field. We also highlight promising approaches based on studies of both
      parasite and host during infection. Ultimately, this knowledge may inform future
      broad spectrum strategies for protecting crops from such pathogens. 

PMID- 24586117
TI  - How brain circuits adapt to changes in sensory experience.

PMID- 24586120
TI  - Effect of water, sanitation, and hygiene on the prevention of trachoma: a
      systematic review and meta-analysis.
AB  - BACKGROUND: Trachoma is the world's leading cause of infectious blindness. The
      World Health Organization (WHO) has endorsed the SAFE strategy in order to
      eliminate blindness due to trachoma by 2020 through "surgery," "antibiotics,"
      "facial cleanliness," and "environmental improvement." While the S and A
      components have been widely implemented, evidence and specific targets are
      lacking for the F and E components, of which water, sanitation, and hygiene
      (WASH) are critical elements. Data on the impact of WASH on trachoma are needed
      to support policy and program recommendations. Our objective was to
      systematically review the literature and conduct meta-analyses where possible to
      report the effects of WASH conditions on trachoma and identify research gaps.
      METHODS AND FINDINGS: We systematically searched PubMed, Embase, ISI Web of
      Knowledge, MedCarib, Lilacs, REPIDISCA, DESASTRES, and African Index Medicus
      databases through October 27, 2013 with no restrictions on language or year of
      publication. Studies were eligible for inclusion if they reported a measure of
      the effect of WASH on trachoma, either active disease indicated by observed signs
      of trachomatous inflammation or Chlamydia trachomatis infection diagnosed using
      PCR. We identified 86 studies that reported a measure of the effect of WASH on
      trachoma. To evaluate study quality, we developed a set of criteria derived from
      the GRADE methodology. Publication bias was assessed using funnel plots. If three
      or more studies reported measures of effect for a comparable WASH exposure and
      trachoma outcome, we conducted a random-effects meta-analysis. We conducted 15
      meta-analyses for specific exposure-outcome pairs. Access to sanitation was
      associated with lower trachoma as measured by the presence of trachomatous
      inflammation-follicular or trachomatous inflammation-intense (TF/TI) (odds ratio
      [OR] 0.85, 95% CI 0.75-0.95) and C. trachomatis infection (OR 0.67, 95% CI 0.55
      0.78). Having a clean face was significantly associated with reduced odds of
      TF/TI (OR 0.42, 95% CI 0.32-0.52), as were facial cleanliness indicators lack of
      ocular discharge (OR 0.42, 95% CI 0.23-0.61) and lack of nasal discharge (OR
      0.62, 95% CI 0.52-0.72). Facial cleanliness indicators were also associated with
      reduced odds of C. trachomatis infection: lack of ocular discharge (OR 0.40, 95%
      CI 0.31-0.49) and lack of nasal discharge (OR 0.56, 95% CI 0.37-0.76). Other
      hygiene factors found to be significantly associated with reduced TF/TI included
      face washing at least once daily (OR 0.76, 95% CI 0.57-0.96), face washing at
      least twice daily (OR 0.85, 95% CI 0.80-0.90), soap use (OR 0.76, 95% CI 0.59
      0.93), towel use (OR 0.65, 95% CI 0.53-0.78), and daily bathing practices (OR
      0.76, 95% CI 0.53-0.99). Living within 1 km of a water source was not found to be
      significantly associated with TF/TI or C. trachomatis infection, and the use of
      sanitation facilities was not found to be significantly associated with TF/TI.
      CONCLUSIONS: We found strong evidence to support F and E components of the SAFE
      strategy. Though limitations included moderate to high heterogenity, low study
      quality, and the lack of standard definitions, these findings support the
      importance of WASH in trachoma elimination strategies and the need for the
      development of standardized approaches to measuring WASH in trachoma control
      programs.

PMID- 24586121
TI  - Biomarker profiling by nuclear magnetic resonance spectroscopy for the prediction
      of all-cause mortality: an observational study of 17,345 persons.
AB  - BACKGROUND: Early identification of ambulatory persons at high short-term risk of
      death could benefit targeted prevention. To identify biomarkers for all-cause
      mortality and enhance risk prediction, we conducted high-throughput profiling of
      blood specimens in two large population-based cohorts. METHODS AND FINDINGS: 106
      candidate biomarkers were quantified by nuclear magnetic resonance spectroscopy
      of non-fasting plasma samples from a random subset of the Estonian Biobank (n =
      9,842; age range 18-103 y; 508 deaths during a median of 5.4 y of follow-up).
      Biomarkers for all-cause mortality were examined using stepwise proportional
      hazards models. Significant biomarkers were validated and incremental predictive
      utility assessed in a population-based cohort from Finland (n = 7,503; 176 deaths
      during 5 y of follow-up). Four circulating biomarkers predicted the risk of all
      cause mortality among participants from the Estonian Biobank after adjusting for
      conventional risk factors: alpha-1-acid glycoprotein (hazard ratio [HR] 1.67 per
      1-standard deviation increment, 95% CI 1.53-1.82, p = 5*10-31), albumin (HR 0.70,
      95% CI 0.65-0.76, p = 2*10-18), very-low-density lipoprotein particle size (HR
      0.69, 95% CI 0.62-0.77, p = 3*10-12), and citrate (HR 1.33, 95% CI 1.21-1.45, p =
      5*10-10). All four biomarkers were predictive of cardiovascular mortality, as
      well as death from cancer and other nonvascular diseases. One in five
      participants in the Estonian Biobank cohort with a biomarker summary score within
      the highest percentile died during the first year of follow-up, indicating
      prominent systemic reflections of frailty. The biomarker associations all
      replicated in the Finnish validation cohort. Including the four biomarkers in a
      risk prediction score improved risk assessment for 5-y mortality (increase in C
      statistics 0.031, p = 0.01; continuous reclassification improvement 26.3%, p =
      0.001). CONCLUSIONS: Biomarker associations with cardiovascular, nonvascular, and
      cancer mortality suggest novel systemic connectivities across seemingly disparate
      morbidities. The biomarker profiling improved prediction of the short-term risk
      of death from all causes above established risk factors. Further investigations
      are needed to clarify the biological mechanisms and the utility of these
      biomarkers for guiding screening and prevention.

PMID- 24586123
TI  - Incident HIV during pregnancy and postpartum and risk of mother-to-child HIV
      transmission: a systematic review and meta-analysis.
AB  - BACKGROUND: Women may have persistent risk of HIV acquisition during pregnancy
      and postpartum. Estimating risk of HIV during these periods is important to
      inform optimal prevention approaches. We performed a systematic review and meta
      analysis to estimate maternal HIV incidence during pregnancy/postpartum and to
      compare mother-to-child HIV transmission (MTCT) risk among women with incident
      versus chronic infection. METHODS AND FINDINGS: We searched PubMed, Embase, and
      AIDS-related conference abstracts between January 1, 1980, and October 31, 2013,
      for articles and abstracts describing HIV acquisition during
      pregnancy/postpartum. The inclusion criterion was studies with data on recent HIV
      during pregnancy/postpartum. Random effects models were constructed to pool HIV
      incidence rates, cumulative HIV incidence, hazard ratios (HRs), or odds ratios
      (ORs) summarizing the association between pregnancy/postpartum status and HIV
      incidence, and MTCT risk and rates. Overall, 1,176 studies met the search
      criteria, of which 78 met the inclusion criterion, and 47 contributed data. Using
      data from 19 cohorts representing 22,803 total person-years, the pooled HIV
      incidence rate during pregnancy/postpartum was 3.8/100 person-years (95% CI 3.0
      4.6): 4.7/100 person-years during pregnancy and 2.9/100 person-years postpartum
      (p = 0.18). Pooled cumulative HIV incidence was significantly higher in African
      than non-African countries (3.6% versus 0.3%, respectively; p<0.001). Risk of HIV
      was not significantly higher among pregnant (HR 1.3, 95% CI 0.5-2.1) or
      postpartum women (HR 1.1, 95% CI 0.6-1.6) than among non-pregnant/non-postpartum
      women in five studies with available data. In African cohorts, MTCT risk was
      significantly higher among women with incident versus chronic HIV infection in
      the postpartum period (OR 2.9, 95% CI 2.2-3.9) or in pregnancy/postpartum periods
      combined (OR 2.3, 95% CI 1.2-4.4). However, the small number of studies limited
      power to detect associations and sources of heterogeneity. CONCLUSIONS: Pregnancy
      and the postpartum period are times of persistent HIV risk, at rates similar to
      "high risk" cohorts. MTCT risk was elevated among women with incident infections.
      Detection and prevention of incident HIV in pregnancy/postpartum should be
      prioritized, and is critical to decrease MTCT.

PMID- 24586124
TI  - Combining experiments and simulations using the maximum entropy principle.
AB  - A key component of computational biology is to compare the results of computer
      modelling with experimental measurements. Despite substantial progress in the
      models and algorithms used in many areas of computational biology, such
      comparisons sometimes reveal that the computations are not in quantitative
      agreement with experimental data. The principle of maximum entropy is a general
      procedure for constructing probability distributions in the light of new data,
      making it a natural tool in cases when an initial model provides results that are
      at odds with experiments. The number of maximum entropy applications in our field
      has grown steadily in recent years, in areas as diverse as sequence analysis,
      structural modelling, and neurobiology. In this Perspectives article, we give a
      broad introduction to the method, in an attempt to encourage its further
      adoption. The general procedure is explained in the context of a simple example,
      after which we proceed with a real-world application in the field of molecular
      simulations, where the maximum entropy procedure has recently provided new
      insight. Given the limited accuracy of force fields, macromolecular simulations
      sometimes produce results that are at not in complete and quantitative accordance
      with experiments. A common solution to this problem is to explicitly ensure
      agreement between the two by perturbing the potential energy function towards the
      experimental data. So far, a general consensus for how such perturbations should
      be implemented has been lacking. Three very recent papers have explored this
      problem using the maximum entropy approach, providing both new theoretical and
      practical insights to the problem. We highlight each of these contributions in
      turn and conclude with a discussion on remaining challenges. 

PMID- 24586125
TI  - Learning gene networks under SNP perturbations using eQTL datasets.
AB  - The standard approach for identifying gene networks is based on experimental
      perturbations of gene regulatory systems such as gene knock-out experiments,
      followed by a genome-wide profiling of differential gene expressions. However,
      this approach is significantly limited in that it is not possible to perturb more
      than one or two genes simultaneously to discover complex gene interactions or to
      distinguish between direct and indirect downstream regulations of the
      differentially-expressed genes. As an alternative, genetical genomics study has
      been proposed to treat naturally-occurring genetic variants as potential
      perturbants of gene regulatory system and to recover gene networks via analysis
      of population gene-expression and genotype data. Despite many advantages of
      genetical genomics data analysis, the computational challenge that the effects of
      multifactorial genetic perturbations should be decoded simultaneously from data
      has prevented a widespread application of genetical genomics analysis. In this
      article, we propose a statistical framework for learning gene networks that
      overcomes the limitations of experimental perturbation methods and addresses the
      challenges of genetical genomics analysis. We introduce a new statistical model,
      called a sparse conditional Gaussian graphical model, and describe an efficient
      learning algorithm that simultaneously decodes the perturbations of gene
      regulatory system by a large number of SNPs to identify a gene network along with
      expression quantitative trait loci (eQTLs) that perturb this network. While our
      statistical model captures direct genetic perturbations of gene network, by
      performing inference on the probabilistic graphical model, we obtain detailed
      characterizations of how the direct SNP perturbation effects propagate through
      the gene network to perturb other genes indirectly. We demonstrate our
      statistical method using HapMap-simulated and yeast eQTL datasets. In particular,
      the yeast gene network identified computationally by our method under SNP
      perturbations is well supported by the results from experimental perturbation
      studies related to DNA replication stress response. 

PMID- 24586127
TI  - In silico single-molecule manipulation of DNA with rigid body dynamics.
AB  - We develop a new powerful method to reproduce in silico single-molecule
      manipulation experiments. We demonstrate that flexible polymers such as DNA can
      be simulated using rigid body dynamics thanks to an original implementation of
      Langevin dynamics in an open source library called Open Dynamics Engine. We
      moreover implement a global thermostat which accelerates the simulation sampling
      by two orders of magnitude. We reproduce force-extension as well as rotation
      extension curves of reference experimental studies. Finally, we extend the model
      to simulations where the control parameter is no longer the torsional strain but
      instead the torque, and predict the expected behavior for this case which is
      particularly challenging theoretically and experimentally. 

PMID- 24586126
TI  - tRNA signatures reveal a polyphyletic origin of SAR11 strains among
      alphaproteobacteria.
AB  - Molecular phylogenetics and phylogenomics are subject to noise from horizontal
      gene transfer (HGT) and bias from convergence in macromolecular compositions.
      Extensive variation in size, structure and base composition of
      alphaproteobacterial genomes has complicated their phylogenomics, sparking
      controversy over the origins and closest relatives of the SAR11 strains. SAR11
      are highly abundant, cosmopolitan aquatic Alphaproteobacteria with streamlined,
      A+T-biased genomes. A dominant view holds that SAR11 are monophyletic and related
      to both Rickettsiales and the ancestor of mitochondria. Other studies dispute
      this, finding evidence of a polyphyletic origin of SAR11 with most strains
      distantly related to Rickettsiales. Although careful evolutionary modeling can
      reduce bias and noise in phylogenomic inference, entirely different approaches
      may be useful to extract robust phylogenetic signals from genomes. Here we
      develop simple phyloclassifiers from bioinformatically derived tRNA Class
      Informative Features (CIFs), features predicted to target tRNAs for specific
      interactions within the tRNA interaction network. Our tRNA CIF-based model
      robustly and accurately classifies alphaproteobacterial genomes into one of seven
      undisputed monophyletic orders or families, despite great variability in tRNA
      gene complement sizes and base compositions. Our model robustly rejects monophyly
      of SAR11, classifying all but one strain as Rhizobiales with strong statistical
      support. Yet remarkably, conventional phylogenetic analysis of tRNAs classifies
      all SAR11 strains identically as Rickettsiales. We attribute this discrepancy to
      convergence of SAR11 and Rickettsiales tRNA base compositions. Thus, tRNA CIFs
      appear more robust to compositional convergence than tRNA sequences generally.
      Our results suggest that tRNA-CIF-based phyloclassification is robust to HGT of
      components of the tRNA interaction network, such as aminoacyl-tRNA synthetases.
      We explain why tRNAs are especially advantageous for prediction of traits
      governing macromolecular interactions from genomic data, and why such traits may
      be advantageous in the search for robust signals to address difficult problems in
      classification and phylogeny. 

PMID- 24586128
TI  - The sign rule and beyond: boundary effects, flexibility, and noise correlations
      in neural population codes.
AB  - Over repeat presentations of the same stimulus, sensory neurons show variable
      responses. This "noise" is typically correlated between pairs of cells, and a
      question with rich history in neuroscience is how these noise correlations impact
      the population's ability to encode the stimulus. Here, we consider a very general
      setting for population coding, investigating how information varies as a function
      of noise correlations, with all other aspects of the problem - neural tuning
      curves, etc. - held fixed. This work yields unifying insights into the role of
      noise correlations. These are summarized in the form of theorems, and illustrated
      with numerical examples involving neurons with diverse tuning curves. Our main
      contributions are as follows. (1) We generalize previous results to prove a sign
      rule (SR) - if noise correlations between pairs of neurons have opposite signs
      vs. their signal correlations, then coding performance will improve compared to
      the independent case. This holds for three different metrics of coding
      performance, and for arbitrary tuning curves and levels of heterogeneity. This
      generality is true for our other results as well. (2) As also pointed out in the
      literature, the SR does not provide a necessary condition for good coding. We
      show that a diverse set of correlation structures can improve coding. Many of
      these violate the SR, as do experimentally observed correlations. There is
      structure to this diversity: we prove that the optimal correlation structures
      must lie on boundaries of the possible set of noise correlations. (3) We provide
      a novel set of necessary and sufficient conditions, under which the coding
      performance (in the presence of noise) will be as good as it would be if there
      were no noise present at all. 

PMID- 24586129
TI  - Escherichia coli peptidoglycan structure and mechanics as predicted by atomic
      scale simulations.
AB  - Bacteria face the challenging requirement to maintain their shape and avoid
      rupture due to the high internal turgor pressure, but simultaneously permit the
      import and export of nutrients, chemical signals, and virulence factors. The
      bacterial cell wall, a mesh-like structure composed of cross-linked strands of
      peptidoglycan, fulfills both needs by being semi-rigid, yet sufficiently porous
      to allow diffusion through it. How the mechanical properties of the cell wall are
      determined by the molecular features and the spatial arrangement of the
      relatively thin strands in the larger cellular-scale structure is not known. To
      examine this issue, we have developed and simulated atomic-scale models of
      Escherichia coli cell walls in a disordered circumferential arrangement. The cell
      wall models are found to possess an anisotropic elasticity, as known
      experimentally, arising from the orthogonal orientation of the glycan strands and
      of the peptide cross-links. Other features such as thickness, pore size, and
      disorder are also found to generally agree with experiments, further supporting
      the disordered circumferential model of peptidoglycan. The validated constructs
      illustrate how mesoscopic structure and behavior emerge naturally from the
      underlying atomic-scale properties and, furthermore, demonstrate the ability of
      all-atom simulations to reproduce a range of macroscopic observables for extended
      polymer meshes. 

PMID- 24586130
TI  - A unified model of heading and path perception in primate MSTd.
AB  - Self-motion, steering, and obstacle avoidance during navigation in the real world
      require humans to travel along curved paths. Many perceptual models have been
      proposed that focus on heading, which specifies the direction of travel along
      straight paths, but not on path curvature, which humans accurately perceive and
      is critical to everyday locomotion. In primates, including humans, dorsal medial
      superior temporal area (MSTd) has been implicated in heading perception. However,
      the majority of MSTd neurons respond optimally to spiral patterns, rather than to
      the radial expansion patterns associated with heading. No existing theory of
      curved path perception explains the neural mechanisms by which humans accurately
      assess path and no functional role for spiral-tuned cells has yet been proposed.
      Here we present a computational model that demonstrates how the continuum of
      observed cells (radial to circular) in MSTd can simultaneously code curvature and
      heading across the neural population. Curvature is encoded through the spirality
      of the most active cell, and heading is encoded through the visuotopic location
      of the center of the most active cell's receptive field. Model curvature and
      heading errors fit those made by humans. Our model challenges the view that the
      function of MSTd is heading estimation, based on our analysis we claim that it is
      primarily concerned with trajectory estimation and the simultaneous
      representation of both curvature and heading. In our model, temporal dynamics
      afford time-history in the neural representation of optic flow, which may
      modulate its structure. This has far-reaching implications for the interpretation
      of studies that assume that optic flow is, and should be, represented as an
      instantaneous vector field. Our results suggest that spiral motion patterns that
      emerge in spatio-temporal optic flow are essential for guiding self-motion along
      complex trajectories, and that cells in MSTd are specifically tuned to extract
      complex trajectory estimation from flow. 

PMID- 24586131
TI  - A virtual infection model quantifies innate effector mechanisms and Candida
      albicans immune escape in human blood.
AB  - Candida albicans bloodstream infection is increasingly frequent and can result in
      disseminated candidiasis associated with high mortality rates. To analyze the
      innate immune response against C. albicans, fungal cells were added to human
      whole-blood samples. After inoculation, C. albicans started to filament and
      predominantly associate with neutrophils, whereas only a minority of fungal cells
      became attached to monocytes. While many parameters of host-pathogen interaction
      were accessible to direct experimental quantification in the whole-blood
      infection assay, others were not. To overcome these limitations, we generated a
      virtual infection model that allowed detailed and quantitative predictions on the
      dynamics of host-pathogen interaction. Experimental time-resolved data were
      simulated using a state-based modeling approach combined with the Monte Carlo
      method of simulated annealing to obtain quantitative predictions on a priori
      unknown transition rates and to identify the main axis of antifungal immunity.
      Results clearly demonstrated a predominant role of neutrophils, mediated by
      phagocytosis and intracellular killing as well as the release of antifungal
      effector molecules upon activation, resulting in extracellular fungicidal
      activity. Both mechanisms together account for almost [Formula: see text] of C.
      albicans killing, clearly proving that beside being present in larger numbers
      than other leukocytes, neutrophils functionally dominate the immune response
      against C. albicans in human blood. A fraction of C. albicans cells escaped
      phagocytosis and remained extracellular and viable for up to four hours. This
      immune escape was independent of filamentation and fungal activity and not linked
      to exhaustion or inactivation of innate immune cells. The occurrence of C.
      albicans cells being resistant against phagocytosis may account for the high
      proportion of dissemination in C. albicans bloodstream infection. Taken together,
      iterative experiment-model-experiment cycles allowed quantitative analyses of the
      interplay between host and pathogen in a complex environment like human blood. 

PMID- 24586132
TI  - GAGA: a new algorithm for genomic inference of geographic ancestry reveals fine
      level population substructure in Europeans.
AB  - Attempts to detect genetic population substructure in humans are troubled by the
      fact that the vast majority of the total amount of observed genetic variation is
      present within populations rather than between populations. Here we introduce a
      new algorithm for transforming a genetic distance matrix that reduces the within
      population variation considerably. Extensive computer simulations revealed that
      the transformed matrix captured the genetic population differentiation better
      than the original one which was based on the T1 statistic. In an empirical
      genomic data set comprising 2,457 individuals from 23 different European
      subpopulations, the proportion of individuals that were determined as a genetic
      neighbour to another individual from the same sampling location increased from
      25% with the original matrix to 52% with the transformed matrix. Similarly, the
      percentage of genetic variation explained between populations by means of
      Analysis of Molecular Variance (AMOVA) increased from 1.62% to 7.98%.
      Furthermore, the first two dimensions of a classical multidimensional scaling
      (MDS) using the transformed matrix explained 15% of the variance, compared to
      0.7% obtained with the original matrix. Application of MDS with Mclust, SPA with
      Mclust, and GemTools algorithms to the same dataset also showed that the
      transformed matrix gave a better association of the genetic clusters with the
      sampling locations, and particularly so when it was used in the AMOVA framework
      with a genetic algorithm. Overall, the new matrix transformation introduced here
      substantially reduces the within population genetic differentiation, and can be
      broadly applied to methods such as AMOVA to enhance their sensitivity to reveal
      population substructure. We herewith provide a publically available
      (http://www.erasmusmc.nl/fmb/resources/GAGA) model-free method for improved
      genetic population substructure detection that can be applied to human as well as
      any other species data in future studies relevant to evolutionary biology,
      behavioural ecology, medicine, and forensics. 

PMID- 24586133
TI  - Differential adhesion between moving particles as a mechanism for the evolution
      of social groups.
AB  - The evolutionary stability of cooperative traits, that are beneficial to other
      individuals but costly to their carrier, is considered possible only through the
      establishment of a sufficient degree of assortment between cooperators. Chimeric
      microbial populations, characterized by simple interactions between unrelated
      individuals, restrain the applicability of standard mechanisms generating such
      assortment, in particular when cells disperse between successive reproductive
      events such as happens in Dicyostelids and Myxobacteria. In this paper, we
      address the evolutionary dynamics of a costly trait that enhances attachment to
      others as well as group cohesion. By modeling cells as self-propelled particles
      moving on a plane according to local interaction forces and undergoing cycles of
      aggregation, reproduction and dispersal, we show that blind differential adhesion
      provides a basis for assortment in the process of group formation. When
      reproductive performance depends on the social context of players, evolution by
      natural selection can lead to the success of the social trait, and to the
      concomitant emergence of sizeable groups. We point out the conditions on the
      microscopic properties of motion and interaction that make such evolutionary
      outcome possible, stressing that the advent of sociality by differential adhesion
      is restricted to specific ecological contexts. Moreover, we show that the
      aggregation process naturally implies the existence of non-aggregated particles,
      and highlight their crucial evolutionary role despite being largely neglected in
      theoretical models for the evolution of sociality. 

PMID- 24586135
TI  - Ten simple rules for running interactive workshops.

PMID- 24586134
TI  - Pathway thermodynamics highlights kinetic obstacles in central metabolism.
AB  - In metabolism research, thermodynamics is usually used to determine the
      directionality of a reaction or the feasibility of a pathway. However, the
      relationship between thermodynamic potentials and fluxes is not limited to
      questions of directionality: thermodynamics also affects the kinetics of
      reactions through the flux-force relationship, which states that the logarithm of
      the ratio between the forward and reverse fluxes is directly proportional to the
      change in Gibbs energy due to a reaction (DeltarG'). Accordingly, if an enzyme
      catalyzes a reaction with a DeltarG' of -5.7 kJ/mol then the forward flux will be
      roughly ten times the reverse flux. As DeltarG' approaches equilibrium (DeltarG'
      = 0 kJ/mol), exponentially more enzyme counterproductively catalyzes the reverse
      reaction, reducing the net rate at which the reaction proceeds. Thus, the enzyme
      level required to achieve a given flux increases dramatically near equilibrium.
      Here, we develop a framework for quantifying the degree to which pathways suffer
      these thermodynamic limitations on flux. For each pathway, we calculate a single
      thermodynamically-derived metric (the Max-min Driving Force, MDF), which enables
      objective ranking of pathways by the degree to which their flux is constrained by
      low thermodynamic driving force. Our framework accounts for the effect of pH,
      ionic strength and metabolite concentration ranges and allows us to quantify how
      alterations to the pathway structure affect the pathway's thermodynamics.
      Applying this methodology to pathways of central metabolism sheds light on some
      of their features, including metabolic bypasses (e.g., fermentation pathways
      bypassing substrate-level phosphorylation), substrate channeling (e.g., of
      oxaloacetate from malate dehydrogenase to citrate synthase), and use of
      alternative cofactors (e.g., quinone as an electron acceptor instead of NAD). The
      methods presented here place another arrow in metabolic engineers' quiver,
      providing a simple means of evaluating the thermodynamic and kinetic quality of
      different pathway chemistries that produce the same molecules. 

PMID- 24586136
TI  - k-OptForce: integrating kinetics with flux balance analysis for strain design.
AB  - Computational strain design protocols aim at the system-wide identification of
      intervention strategies for the enhanced production of biochemicals in
      microorganisms. Existing approaches relying solely on stoichiometry and
      rudimentary constraint-based regulation overlook the effects of metabolite
      concentrations and substrate-level enzyme regulation while identifying metabolic
      interventions. In this paper, we introduce k-OptForce, which integrates the
      available kinetic descriptions of metabolic steps with stoichiometric models to
      sharpen the prediction of intervention strategies for improving the bio
      production of a chemical of interest. It enables identification of a minimal set
      of interventions comprised of both enzymatic parameter changes (for reactions
      with available kinetics) and reaction flux changes (for reactions with only
      stoichiometric information). Application of k-OptForce to the overproduction of L
      serine in E. coli and triacetic acid lactone (TAL) in S. cerevisiae revealed that
      the identified interventions tend to cause less dramatic rearrangements of the
      flux distribution so as not to violate concentration bounds. In some cases the
      incorporation of kinetic information leads to the need for additional
      interventions as kinetic expressions render stoichiometry-only derived
      interventions infeasible by violating concentration bounds, whereas in other
      cases the kinetic expressions impart flux changes that favor the overproduction
      of the target product thereby requiring fewer direct interventions. A sensitivity
      analysis on metabolite concentrations shows that the required number of
      interventions can be significantly affected by changing the imposed bounds on
      metabolite concentrations. Furthermore, k-OptForce was capable of finding non
      intuitive interventions aiming at alleviating the substrate-level inhibition of
      key enzymes in order to enhance the flux towards the product of interest, which
      cannot be captured by stoichiometry-alone analysis. This study paves the way for
      the integrated analysis of kinetic and stoichiometric models and enables
      elucidating system-wide metabolic interventions while capturing regulatory and
      kinetic effects. 

PMID- 24586137
TI  - Optimal recall from bounded metaplastic synapses: predicting functional
      adaptations in hippocampal area CA3.
AB  - A venerable history of classical work on autoassociative memory has significantly
      shaped our understanding of several features of the hippocampus, and most
      prominently of its CA3 area, in relation to memory storage and retrieval.
      However, existing theories of hippocampal memory processing ignore a key
      biological constraint affecting memory storage in neural circuits: the bounded
      dynamical range of synapses. Recent treatments based on the notion of
      metaplasticity provide a powerful model for individual bounded synapses; however,
      their implications for the ability of the hippocampus to retrieve memories well
      and the dynamics of neurons associated with that retrieval are both unknown.
      Here, we develop a theoretical framework for memory storage and recall with
      bounded synapses. We formulate the recall of a previously stored pattern from a
      noisy recall cue and limited-capacity (and therefore lossy) synapses as a
      probabilistic inference problem, and derive neural dynamics that implement
      approximate inference algorithms to solve this problem efficiently. In
      particular, for binary synapses with metaplastic states, we demonstrate for the
      first time that memories can be efficiently read out with biologically plausible
      network dynamics that are completely constrained by the synaptic plasticity rule,
      and the statistics of the stored patterns and of the recall cue. Our theory
      organises into a coherent framework a wide range of existing data about the
      regulation of excitability, feedback inhibition, and network oscillations in area
      CA3, and makes novel and directly testable predictions that can guide future
      experiments. 

PMID- 24586138
TI  - A combination of transcriptional and microRNA regulation improves the stability
      of the relative concentrations of target genes.
AB  - It is well known that, under suitable conditions, microRNAs are able to fine tune
      the relative concentration of their targets to any desired value. We show that
      this function is particularly effective when one of the targets is a
      Transcription Factor (TF) which regulates the other targets. This combination
      defines a new class of feed-forward loops (FFLs) in which the microRNA plays the
      role of master regulator. Using both deterministic and stochastic equations, we
      show that these FFLs are indeed able not only to fine-tune the TF/target ratio to
      any desired value as a function of the miRNA concentration but also, thanks to
      the peculiar topology of the circuit, to ensure the stability of this ratio
      against stochastic fluctuations. These two effects are due to the interplay
      between the direct transcriptional regulation and the indirect TF/Target
      interaction due to competition of TF and target for miRNA binding (the so called
      "sponge effect"). We then perform a genome wide search of these FFLs in the human
      regulatory network and show that they are characterized by a very peculiar
      enrichment pattern. In particular, they are strongly enriched in all the
      situations in which the TF and its target have to be precisely kept at the same
      concentration notwithstanding the environmental noise. As an example we discuss
      the FFL involving E2F1 as Transcription Factor, RB1 as target and miR-17 family
      as master regulator. These FFLs ensure a tight control of the E2F/RB ratio which
      in turns ensures the stability of the transition from the G0/G1 to the S phase in
      quiescent cells. 

PMID- 24586140
TI  - Workshops: a great way to enhance and supplement a degree.
AB  - As part of the International Society for Computational Biology Student Council
      (ISCB-SC), Regional Student Groups (RSGs) have helped organise workshops in the
      emerging fields of bioinformatics and computational biology. Workshops are a
      great way for students to gain hands-on experience and rapidly acquire knowledge
      in advanced research topics where curriculum-based education is yet to be
      developed. RSG workshops have improved dissemination of knowledge of the latest
      bioinformatics techniques and resources among student communities and young
      scientists, especially in developing nations. This article highlights some of the
      benefits and challenges encountered while running RSG workshops. Examples cover a
      variety of subjects, including introductory bioinformatics and advanced
      bioinformatics, as well as soft skills such as networking, career development,
      and socializing. The collective experience condensed in this article is a useful
      starting point for students wishing to organise their own tailor-made workshops. 

PMID- 24586139
TI  - A novel Bayesian method for detection of APOBEC3-mediated hypermutation and its
      application to zoonotic transmission of simian foamy viruses.
AB  - Simian Foamy Virus (SFV) can be transmitted from non-human primates (NHP) to
      humans. However, there are no documented cases of human to human transmission,
      and significant differences exist between infection in NHP and human hosts. The
      mechanism for these between-host differences is not completely understood. In
      this paper we develop a new Bayesian approach to the detection of APOBEC3
      mediated hypermutation, and use it to compare SFV sequences from human and NHP
      hosts living in close proximity in Bangladesh. We find that human APOBEC3G can
      induce genetic changes that may prevent SFV replication in infected humans in
      vivo. 

PMID- 24586143
TI  - The microRNAs in an ancient protist repress the variant-specific surface protein
      expression by targeting the entire coding sequence.
AB  - microRNAs (miRNA) have been detected in the deeply branched protist, Giardia
      lamblia, and shown to repress expression of the family of variant-specific
      surface proteins (VSPs), only one of which is expressed in Giardia trophozoite at
      a given time. Three next-generation sequencing libraries of Giardia Argonaute
      associated small RNAs were constructed and analyzed. Analysis of the libraries
      identified a total of 99 new putative miRNAs with a size primarily in the 26 nt
      range similar to the size previously predicted by the Giardia Dicer crystal
      structure and identified by our own studies. Bioinformatic analysis identified
      multiple putative miRNA target sites in the mRNAs of all 73 VSPs. The effect of
      miRNA target sites within a defined 3'-region were tested on two vsp mRNAs. All
      the miRNAs showed partial repression of the corresponding vsp expression and were
      additive when the targeting sites were separately located. But the combined
      repression still falls short of 100%. Two other relatively short vsp mRNAs with
      15 and 11 putative miRNA target sites identified throughout their ORFs were
      tested with their corresponding miRNAs. The results indicate that; (1) near 100%
      repression of vsp mRNA expression can be achieved through the combined action of
      multiple miRNAs on target sites located throughout the ORF; (2) the miRNA
      machinery could be instrumental in repressing the expression of vsp genes in
      Giardia; (3) this is the first time that all the miRNA target sites in the entire
      ORF of a mRNA have been tested and shown to be functional. 

PMID- 24586145
TI  - Clustering of pattern recognition receptors for fungal detection.

PMID- 24586144
TI  - A compositional look at the human gastrointestinal microbiome and immune
      activation parameters in HIV infected subjects.
AB  - HIV progression is characterized by immune activation and microbial
      translocation. One factor that may be contributing to HIV progression could be a
      dysbiotic microbiome. We therefore hypothesized that the GI mucosal microbiome is
      altered in HIV patients and this alteration correlates with immune activation in
      HIV. 121 specimens were collected from 21 HIV positive and 22 control human
      subjects during colonoscopy. The composition of the lower gastrointestinal tract
      mucosal and luminal bacterial microbiome was characterized using 16S rDNA
      pyrosequencing and was correlated to clinical parameters as well as immune
      activation and circulating bacterial products in HIV patients on ART. The
      composition of the HIV microbiome was significantly different than that of
      controls; it was less diverse in the right colon and terminal ileum, and was
      characterized by loss of bacterial taxa that are typically considered commensals.
      In HIV samples, there was a gain of some pathogenic bacterial taxa. This is the
      first report characterizing the terminal ileal and colonic mucosal microbiome in
      HIV patients with next generation sequencing. Limitations include use of HIV
      infected subjects on HAART therapy. 

PMID- 24586146
TI  - Malassezia yeasts: how many species infect humans and animals?

PMID- 24586148
TI  - Gem-induced cytoskeleton remodeling increases cellular migration of HTLV-1
      infected cells, formation of infected-to-target T-cell conjugates and viral
      transmission.
AB  - Efficient HTLV-1 viral transmission occurs through cell-to-cell contacts. The Tax
      viral transcriptional activator protein facilitates this process. Using a
      comparative transcriptomic analysis, we recently identified a series of genes up
      regulated in HTLV-1 Tax expressing T-lymphocytes. We focused our attention
      towards genes that are important for cytoskeleton dynamic and thus may possibly
      modulate cell-to-cell contacts. We first demonstrate that Gem, a member of the
      small GTP-binding proteins within the Ras superfamily, is expressed both at the
      RNA and protein levels in Tax-expressing cells and in HTLV-1-infected cell lines.
      Using a series of ChIP assays, we show that Tax recruits CREB and CREB Binding
      Protein (CBP) onto a c-AMP Responsive Element (CRE) present in the gem promoter.
      This CRE sequence is required to drive Tax-activated gem transcription. Since Gem
      is involved in cytoskeleton remodeling, we investigated its role in infected
      cells motility. We show that Gem co-localizes with F-actin and is involved both
      in T-cell spontaneous cell migration as well as chemotaxis in the presence of SDF
      1/CXCL12. Importantly, gem knock-down in HTLV-1-infected cells decreases cell
      migration and conjugate formation. Finally, we demonstrate that Gem plays an
      important role in cell-to-cell viral transmission. 

PMID- 24586149
TI  - Interleukin-33 increases antibacterial defense by activation of inducible nitric
      oxide synthase in skin.
AB  - Interleukin-33 (IL-33) is associated with multiple diseases, including asthma,
      rheumatoid arthritis, tissue injuries and infections. Although IL-33 has been
      indicated to be involved in Staphylococcus aureus (S. aureus) wound infection,
      little is known about how IL-33 is regulated as a mechanism to increase host
      defense against skin bacterial infections. To explore the underlying intricate
      mechanism we first evaluated the expression of IL-33 in skin from S. aureus
      infected human patients. Compared to normal controls, IL-33 was abundantly
      increased in skin of S. aureus-infected patients. We next developed a S. aureus
      cutaneous infection mouse model and found that IL-33 was significantly increased
      in dermal macrophages of infected mouse skin. The expression of IL-33 by
      macrophages was induced by staphylococcal peptidoglycan (PGN) and lipoteichoic
      acid (LTA) via activation of toll-like receptor 2(TLR2)-mitogen-activated protein
      kinase (MAPK)-AKT-signal transducer and activator of transcription 3(STAT3)
      signaling pathway as PGN and LTA failed to induce IL-33 in Tlr2-deficient
      peritoneal macrophages, and MAPK,AKT, STAT3 inhibitors significantly decreased
      PGN- or LTA-induced IL-33. IL-33, in turn, acted on macrophages to induce
      microbicidal nitric oxygen (NO) release. This induction was dependent on
      inducible nitric oxide synthase (iNOS) activation, as treatment of macrophages
      with an inhibitor of iNOS, aminoguanidine, significantly decreased IL-33-induced
      NO release. Moreover, aminoguanidine significantly blocked the capacity of IL-33
      to inhibit the growth of S. aureus, and IL-33 silencing in macrophages
      significantly increased the survival of S. aureus in macrophages. Furthermore,
      the administration of IL-33-neutralizing antibody into mouse skin decreased iNOS
      production but increased the survival of S. aureus in skin. These findings reveal
      that IL-33 can promote antimicrobial capacity of dermal macrophages, thus
      enhancing antimicrobial defense against skin bacterial infections.

PMID- 24586147
TI  - Tailored immune responses: novel effector helper T cell subsets in protective
      immunity.
AB  - Differentiation of naive CD4+ cells into functionally distinct effector helper T
      cell subsets, characterised by distinct "cytokine signatures," is a cardinal
      strategy employed by the mammalian immune system to efficiently deal with the
      rapidly evolving array of pathogenic microorganisms encountered by the host.
      Since the T(H)1/T(H)2 paradigm was first described by Mosmann and Coffman,
      research in the field of helper T cell biology has grown exponentially with seven
      functionally unique subsets having now been described. In this review, recent
      insights into the molecular mechanisms that govern differentiation and function
      of effector helper T cell subsets will be discussed in the context of microbial
      infections, with a focus on how these different helper T cell subsets orchestrate
      immune responses tailored to combat the nature of the pathogenic threat
      encountered.

PMID- 24586150
TI  - Protective vaccination against papillomavirus-induced skin tumors under
      immunocompetent and immunosuppressive conditions: a preclinical study using a
      natural outbred animal model.
AB  - Certain cutaneous human papillomaviruses (HPVs), which are ubiquitous and
      acquired early during childhood, can cause a variety of skin tumors and are
      likely involved in the development of non-melanoma skin cancer, especially in
      immunosuppressed patients. Hence, the burden of these clinical manifestations
      demands for a prophylactic approach. To evaluate whether protective efficacy of a
      vaccine is potentially translatable to patients, we used the rodent Mastomys
      coucha that is naturally infected with Mastomys natalensis papillomavirus (MnPV).
      This skin type papillomavirus induces not only benign skin tumours, such as
      papillomas and keratoacanthomas, but also squamous cell carcinomas, thereby
      allowing a straightforward read-out for successful vaccination in a small
      immunocompetent laboratory animal. Here, we examined the efficacy of a virus-like
      particle (VLP)-based vaccine on either previously or newly established
      infections. VLPs raise a strong and long-lasting neutralizing antibody response
      that confers protection even under systemic long-term cyclosporine A treatment.
      Remarkably, the vaccine completely prevents the appearance of benign as well as
      malignant skin tumors. Protection involves the maintenance of a low viral load in
      the skin by an antibody-dependent prevention of virus spread. Our results provide
      first evidence that VLPs elicit an effective immune response in the skin under
      immunocompetent and immunosuppressed conditions in an outbred animal model,
      irrespective of the infection status at the time of vaccination. These findings
      provide the basis for the clinical development of potent vaccination strategies
      against cutaneous HPV infections and HPV-induced tumors, especially in patients
      awaiting organ transplantation. 

PMID- 24586151
TI  - Mycobacterium tuberculosis exploits asparagine to assimilate nitrogen and resist
      acid stress during infection.
AB  - Mycobacterium tuberculosis is an intracellular pathogen. Within macrophages, M.
      tuberculosis thrives in a specialized membrane-bound vacuole, the phagosome,
      whose pH is slightly acidic, and where access to nutrients is limited.
      Understanding how the bacillus extracts and incorporates nutrients from its host
      may help develop novel strategies to combat tuberculosis. Here we show that M.
      tuberculosis employs the asparagine transporter AnsP2 and the secreted
      asparaginase AnsA to assimilate nitrogen and resist acid stress through
      asparagine hydrolysis and ammonia release. While the role of AnsP2 is partially
      spared by yet to be identified transporter(s), that of AnsA is crucial in both
      phagosome acidification arrest and intracellular replication, as an M.
      tuberculosis mutant lacking this asparaginase is ultimately attenuated in
      macrophages and in mice. Our study provides yet another example of the intimate
      link between physiology and virulence in the tubercle bacillus, and identifies a
      novel pathway to be targeted for therapeutic purposes. 

PMID- 24586152
TI  - The secreted triose phosphate isomerase of Brugia malayi is required to sustain
      microfilaria production in vivo.
AB  - Human lymphatic filariasis is a major tropical disease transmitted through
      mosquito vectors which take up microfilarial larvae from the blood of infected
      subjects. Microfilariae are produced by long-lived adult parasites, which also
      release a suite of excretory-secretory products that have recently been subject
      to in-depth proteomic analysis. Surprisingly, the most abundant secreted protein
      of adult Brugia malayi is triose phosphate isomerase (TPI), a glycolytic enzyme
      usually associated with the cytosol. We now show that while TPI is a prominent
      target of the antibody response to infection, there is little antibody-mediated
      inhibition of catalytic activity by polyclonal sera. We generated a panel of
      twenty-three anti-TPI monoclonal antibodies and found only two were able to block
      TPI enzymatic activity. Immunisation of jirds with B. malayi TPI, or mice with
      the homologous protein from the rodent filaria Litomosoides sigmodontis, failed
      to induce neutralising antibodies or protective immunity. In contrast, passive
      transfer of neutralising monoclonal antibody to mice prior to implantation with
      adult B. malayi resulted in 60-70% reductions in microfilarial levels in vivo and
      both oocyte and microfilarial production by individual adult females. The loss of
      fecundity was accompanied by reduced IFNgamma expression by CD4+ T cells and a
      higher proportion of macrophages at the site of infection. Thus, enzymatically
      active TPI plays an important role in the transmission cycle of B. malayi
      filarial parasites and is identified as a potential target for immunological and
      pharmacological intervention against filarial infections.

PMID- 24586153
TI  - Unifying viral genetics and human transportation data to predict the global
      transmission dynamics of human influenza H3N2.
AB  - Information on global human movement patterns is central to spatial
      epidemiological models used to predict the behavior of influenza and other
      infectious diseases. Yet it remains difficult to test which modes of dispersal
      drive pathogen spread at various geographic scales using standard epidemiological
      data alone. Evolutionary analyses of pathogen genome sequences increasingly
      provide insights into the spatial dynamics of influenza viruses, but to date they
      have largely neglected the wealth of information on human mobility, mainly
      because no statistical framework exists within which viral gene sequences and
      empirical data on host movement can be combined. Here, we address this problem by
      applying a phylogeographic approach to elucidate the global spread of human
      influenza subtype H3N2 and assess its ability to predict the spatial spread of
      human influenza A viruses worldwide. Using a framework that estimates the
      migration history of human influenza while simultaneously testing and quantifying
      a range of potential predictive variables of spatial spread, we show that the
      global dynamics of influenza H3N2 are driven by air passenger flows, whereas at
      more local scales spread is also determined by processes that correlate with
      geographic distance. Our analyses further confirm a central role for mainland
      China and Southeast Asia in maintaining a source population for global influenza
      diversity. By comparing model output with the known pandemic expansion of H1N1
      during 2009, we demonstrate that predictions of influenza spatial spread are most
      accurate when data on human mobility and viral evolution are integrated. In
      conclusion, the global dynamics of influenza viruses are best explained by
      combining human mobility data with the spatial information inherent in sampled
      viral genomes. The integrated approach introduced here offers great potential for
      epidemiological surveillance through phylogeographic reconstructions and for
      improving predictive models of disease control. 

PMID- 24586155
TI  - Inflammatory monocytes orchestrate innate antifungal immunity in the lung.
AB  - Aspergillus fumigatus is an environmental fungus that causes invasive
      aspergillosis (IA) in immunocompromised patients. Although -CC-chemokine receptor
      2 (CCR2) and Ly6C-expressing inflammatory monocytes (CCR2+Mo) and their
      derivatives initiate adaptive pulmonary immune responses, their role in
      coordinating innate immune responses in the lung remain poorly defined. Using
      conditional and antibody-mediated cell ablation strategies, we found that CCR2+Mo
      and monocyte-derived dendritic cells (Mo-DCs) are essential for innate defense
      against inhaled conidia. By harnessing fluorescent Aspergillus reporter (FLARE)
      conidia that report fungal cell association and viability in vivo, we identify
      two mechanisms by which CCR2+Mo and Mo-DCs exert innate antifungal activity.
      First, CCR2+Mo and Mo-DCs condition the lung inflammatory milieu to augment
      neutrophil conidiacidal activity. Second, conidial uptake by CCR2+Mo temporally
      coincided with their differentiation into Mo-DCs, a process that resulted in
      direct conidial killing. Our findings illustrate both indirect and direct
      functions for CCR2+Mo and their derivatives in innate antifungal immunity in the
      lung.

PMID- 24586156
TI  - 'Death and axes': unexpected Ca2+ entry phenologs predict new anti-schistosomal
      agents.
AB  - Schistosomiasis is a parasitic flatworm disease that infects 200 million people
      worldwide. The drug praziquantel (PZQ) is the mainstay therapy but the target of
      this drug remains ambiguous. While PZQ paralyses and kills parasitic
      schistosomes, in free-living planarians PZQ caused an unusual axis duplication
      during regeneration to yield two-headed animals. Here, we show that PZQ
      activation of a neuronal Ca2+ channel modulates opposing dopaminergic and
      serotonergic pathways to regulate 'head' structure formation. Surprisingly,
      compounds with efficacy for either bioaminergic network in planarians also
      displayed antischistosomal activity, and reciprocally, agents first identified as
      antischistocidal compounds caused bipolar regeneration in the planarian bioassay.
      These divergent outcomes (death versus axis duplication) result from the same
      Ca2+ entry mechanism, and comprise unexpected Ca2+ phenologs with meaningful
      predictive value. Surprisingly, basic research into axis patterning mechanisms
      provides an unexpected route for discovering novel antischistosomal agents.

PMID- 24586154
TI  - Metabolic reprogramming during purine stress in the protozoan pathogen Leishmania
      donovani.
AB  - The ability of Leishmania to survive in their insect or mammalian host is
      dependent upon an ability to sense and adapt to changes in the microenvironment.
      However, little is known about the molecular mechanisms underlying the parasite
      response to environmental changes, such as nutrient availability. To elucidate
      nutrient stress response pathways in Leishmania donovani, we have used purine
      starvation as the paradigm. The salvage of purines from the host milieu is
      obligatory for parasite replication; nevertheless, purine-starved parasites can
      persist in culture without supplementary purine for over three months, indicating
      that the response to purine starvation is robust and engenders parasite survival
      under conditions of extreme scarcity. To understand metabolic reprogramming
      during purine starvation we have employed global approaches. Whole proteome
      comparisons between purine-starved and purine-replete parasites over a 6-48 h
      span have revealed a temporal and coordinated response to purine starvation.
      Purine transporters and enzymes involved in acquisition at the cell surface are
      upregulated within a few hours of purine removal from the media, while other key
      purine salvage components are upregulated later in the time-course and more
      modestly. After 48 h, the proteome of purine-starved parasites is extensively
      remodeled and adaptations to purine stress appear tailored to deal with both
      purine deprivation and general stress. To probe the molecular mechanisms
      affecting proteome remodeling in response to purine starvation, comparative RNA
      seq analyses, qRT-PCR, and luciferase reporter assays were performed on purine
      starved versus purine-replete parasites. While the regulation of a minority of
      proteins tracked with changes at the mRNA level, for many regulated proteins it
      appears that proteome remodeling during purine stress occurs primarily via
      translational and/or post-translational mechanisms. 

PMID- 24586157
TI  - Inactivation of the host lipin gene accelerates RNA virus replication through
      viral exploitation of the expanded endoplasmic reticulum membrane.
AB  - RNA viruses take advantage of cellular resources, such as membranes and lipids,
      to assemble viral replicase complexes (VRCs) that drive viral replication. The
      host lipins (phosphatidate phosphatases) are particularly interesting because
      these proteins play key roles in cellular decisions about membrane biogenesis
      versus lipid storage. Therefore, we examined the relationship between host lipins
      and tombusviruses, based on yeast model host. We show that deletion of PAH1
      (phosphatidic acid phosphohydrolase), which is the single yeast homolog of the
      lipin gene family of phosphatidate phosphatases, whose inactivation is
      responsible for proliferation and expansion of the endoplasmic reticulum (ER)
      membrane, facilitates robust RNA virus replication in yeast. We document
      increased tombusvirus replicase activity in pah1Delta yeast due to the efficient
      assembly of VRCs. We show that the ER membranes generated in pah1Delta yeast is
      efficiently subverted by this RNA virus, thus emphasizing the connection between
      host lipins and RNA viruses. Thus, instead of utilizing the peroxisomal membranes
      as observed in wt yeast and plants, TBSV readily switches to the vastly expanded
      ER membranes in lipin-deficient cells to build VRCs and support increased level
      of viral replication. Over-expression of the Arabidopsis Pah2p in Nicotiana
      benthamiana decreased tombusvirus accumulation, validating that our findings are
      also relevant in a plant host. Over-expression of AtPah2p also inhibited the ER
      based replication of another plant RNA virus, suggesting that the role of lipins
      in RNA virus replication might include several more eukaryotic viruses. 

PMID- 24586158
TI  - The post-transcriptional regulator rsmA/csrA activates T3SS by stabilizing the 5'
      UTR of hrpG, the master regulator of hrp/hrc genes, in Xanthomonas.
AB  - The RsmA/CsrA family of the post-transcriptional regulators of bacteria is
      involved in the regulation of many cellular processes, including pathogenesis. In
      this study, we demonstrated that rsmA not only is required for the full virulence
      of the phytopathogenic bacterium Xanthomonas citri subsp. citri (XCC) but also
      contributes to triggering the hypersensitive response (HR) in non-host plants.
      Deletion of rsmA resulted in significantly reduced virulence in the host plant
      sweet orange and a delayed and weakened HR in the non-host plant Nicotiana
      benthamiana. Microarray, quantitative reverse-transcription PCR, western
      blotting, and GUS assays indicated that RsmA regulates the expression of the type
      3 secretion system (T3SS) at both transcriptional and post-transcriptional
      levels. The regulation of T3SS by RsmA is a universal phenomenon in T3SS
      containing bacteria, but the specific mechanism seems to depend on the
      interaction between a particular bacterium and its hosts. For Xanthomonads, the
      mechanism by which RsmA activates T3SS remains unknown. Here, we show that RsmA
      activates the expression of T3SS-encoding hrp/hrc genes by directly binding to
      the 5' untranslated region (UTR) of hrpG, the master regulator of the hrp/hrc
      genes in XCC. RsmA stabilizes hrpG mRNA, leading to increased accumulation of
      HrpG proteins and subsequently, the activation of hrp/hrc genes. The activation
      of the hrp/hrc genes by RsmA via HrpG was further supported by the observation
      that ectopic overexpression of hrpG in an rsmA mutant restored its ability to
      cause disease in host plants and trigger HR in non-host plants. RsmA also
      stabilizes the transcripts of another T3SS-associated hrpD operon by directly
      binding to the 5' UTR region. Taken together, these data revealed that RsmA
      primarily activates T3SS by acting as a positive regulator of hrpG and that this
      regulation is critical to the pathogenicity of XCC. 

PMID- 24586160
TI  - Induction of type I interferon signaling determines the relative pathogenicity of
      Staphylococcus aureus strains.
AB  - The tremendous success of S. aureus as a human pathogen has been explained
      primarily by its array of virulence factors that enable the organism to evade
      host immunity. Perhaps equally important, but less well understood, is the
      importance of the intensity of the host response in determining the extent of
      pathology induced by S. aureus infection, particularly in the pathogenesis of
      pneumonia. We compared the pathogenesis of infection caused by two
      phylogenetically and epidemiologically distinct strains of S. aureus whose
      behavior in humans has been well characterized. Induction of the type I IFN
      cascade by strain 502A, due to a NOD2-IRF5 pathway, was the major factor in
      causing severe pneumonia and death in a murine model of pneumonia and was
      associated with autolysis and release of peptidogylcan. In contrast to USA300,
      502A was readily eliminated from epithelial surfaces in vitro. Nonetheless, 502A
      caused significantly increased tissue damage due to the organisms that were able
      to invade systemically and trigger type I IFN responses, and this was ameliorated
      in Ifnar-/- mice. The success of USA300 to cause invasive infection appears to
      depend upon its resistance to eradication from epithelial surfaces, but not
      production of specific toxins. Our studies illustrate the important and highly
      variable role of type I IFN signaling within a species and suggest that targeted
      immunomodulation of specific innate immune signaling cascades may be useful to
      prevent the excessive morbidity associated with S. aureus pneumonia.

PMID- 24586159
TI  - Identification of host-targeted small molecules that restrict intracellular
      Mycobacterium tuberculosis growth.
AB  - Mycobacterium tuberculosis remains a significant threat to global health.
      Macrophages are the host cell for M. tuberculosis infection, and although
      bacteria are able to replicate intracellularly under certain conditions, it is
      also clear that macrophages are capable of killing M. tuberculosis if
      appropriately activated. The outcome of infection is determined at least in part
      by the host-pathogen interaction within the macrophage; however, we lack a
      complete understanding of which host pathways are critical for bacterial survival
      and replication. To add to our understanding of the molecular processes involved
      in intracellular infection, we performed a chemical screen using a high-content
      microscopic assay to identify small molecules that restrict mycobacterial growth
      in macrophages by targeting host functions and pathways. The identified host
      targeted inhibitors restrict bacterial growth exclusively in the context of
      macrophage infection and predominantly fall into five categories: G-protein
      coupled receptor modulators, ion channel inhibitors, membrane transport proteins,
      anti-inflammatories, and kinase modulators. We found that fluoxetine, a selective
      serotonin reuptake inhibitor, enhances secretion of pro-inflammatory cytokine TNF
      alpha and induces autophagy in infected macrophages, and gefitinib, an inhibitor
      of the Epidermal Growth Factor Receptor (EGFR), also activates autophagy and
      restricts growth. We demonstrate that during infection signaling through EGFR
      activates a p38 MAPK signaling pathway that prevents macrophages from effectively
      responding to infection. Inhibition of this pathway using gefitinib during in
      vivo infection reduces growth of M. tuberculosis in the lungs of infected mice.
      Our results support the concept that screening for inhibitors using intracellular
      models results in the identification of tool compounds for probing pathways
      during in vivo infection and may also result in the identification of new anti
      tuberculosis agents that work by modulating host pathways. Given the existing
      experience with some of our identified compounds for other therapeutic
      indications, further clinically-directed study of these compounds is merited. 

PMID- 24586161
TI  - AvrBsT acetylates Arabidopsis ACIP1, a protein that associates with microtubules
      and is required for immunity.
AB  - Bacterial pathogens of plant and animals share a homologous group of virulence
      factors, referred to as the YopJ effector family, which are translocated by the
      type III secretion (T3S) system into host cells during infection. Recent work
      indicates that some of these effectors encode acetyltransferases that suppress
      host immunity. The YopJ-like protein AvrBsT is known to activate effector
      triggered immunity (ETI) in Arabidopsis thaliana Pi-0 plants; however, the nature
      of its enzymatic activity and host target(s) has remained elusive. Here we report
      that AvrBsT possesses acetyltransferase activity and acetylates ACIP1 (for
      ACETYLATED INTERACTING PROTEIN1), an unknown protein from Arabidopsis. Genetic
      studies revealed that Arabidopsis ACIP family members are required for both
      pathogen-associated molecular pattern (PAMP)-triggered immunity and AvrBsT
      triggered ETI during Pseudomonas syringae pathovar tomato DC3000 (Pst DC3000)
      infection. Microscopy studies revealed that ACIP1 is associated with punctae on
      the cell cortex and some of these punctae co-localize with microtubules. These
      structures were dramatically altered during infection. Pst DC3000 or Pst DC3000
      AvrRpt2 infection triggered the formation of numerous, small ACIP1 punctae and
      rods. By contrast, Pst DC3000 AvrBsT infection primarily triggered the formation
      of large GFP-ACIP1 aggregates, in an acetyltransferase-dependent manner. Our data
      reveal that members of the ACIP family are new components of the defense
      machinery required for anti-bacterial immunity. They also suggest that AvrBsT
      dependent acetylation in planta alters ACIP1's defense function, which is linked
      to the activation of ETI. 

PMID- 24586162
TI  - The Chlamydia trachomatis type III secretion chaperone Slc1 engages multiple
      early effectors, including TepP, a tyrosine-phosphorylated protein required for
      the recruitment of CrkI-II to nascent inclusions and innate immune signaling.
AB  - Chlamydia trachomatis, the causative agent of trachoma and sexually transmitted
      infections, employs a type III secretion (T3S) system to deliver effector
      proteins into host epithelial cells to establish a replicative vacuole. Aside
      from the phosphoprotein TARP, a Chlamydia effector that promotes actin re
      arrangements, very few factors mediating bacterial entry and early inclusion
      establishment have been characterized. Like many T3S effectors, TARP requires a
      chaperone (Slc1) for efficient translocation into host cells. In this study, we
      defined proteins that associate with Slc1 in invasive C. trachomatis elementary
      bodies (EB) by immunoprecipitation coupled with mass spectrometry. We identified
      Ct875, a new Slc1 client protein and T3S effector, which we renamed TepP
      (Translocated early phosphoprotein). We provide evidence that T3S effectors form
      large molecular weight complexes with Scl1 in vitro and that Slc1 enhances their
      T3S-dependent secretion in a heterologous Yersinia T3S system. We demonstrate
      that TepP is translocated early during bacterial entry into epithelial cells and
      is phosphorylated at tyrosine residues by host kinases. However, TepP
      phosphorylation occurs later than TARP, which together with the finding that Slc1
      preferentially engages TARP in EBs leads us to postulate that these effectors are
      translocated into the host cell at different stages during C. trachomatis
      invasion. TepP co-immunoprecipitated with the scaffolding proteins CrkI-II during
      infection and Crk was recruited to EBs at entry sites where it remained
      associated with nascent inclusions. Importantly, C. trachomatis mutants lacking
      TepP failed to recruit CrkI-II to inclusions, providing genetic confirmation of a
      direct role for this effector in the recruitment of a host factor. Finally,
      endocervical epithelial cells infected with a tepP mutant showed altered
      expression of a subset of genes associated with innate immune responses. We
      propose a model wherein TepP acts downstream of TARP to recruit scaffolding
      proteins at entry sites to initiate and amplify signaling cascades important for
      the regulation of innate immune responses to Chlamydia. 

PMID- 24586163
TI  - Clonal expansion during Staphylococcus aureus infection dynamics reveals the
      effect of antibiotic intervention.
AB  - To slow the inexorable rise of antibiotic resistance we must understand how drugs
      impact on pathogenesis and influence the selection of resistant clones.
      Staphylococcus aureus is an important human pathogen with populations of
      antibiotic-resistant bacteria in hospitals and the community. Host phagocytes
      play a crucial role in controlling S. aureus infection, which can lead to a
      population "bottleneck" whereby clonal expansion of a small fraction of the
      initial inoculum founds a systemic infection. Such population dynamics may have
      important consequences on the effect of antibiotic intervention. Low doses of
      antibiotics have been shown to affect in vitro growth and the generation of
      resistant mutants over the long term, however whether this has any in vivo
      relevance is unknown. In this work, the population dynamics of S. aureus
      pathogenesis were studied in vivo using antibiotic-resistant strains constructed
      in an isogenic background, coupled with systemic models of infection in both the
      mouse and zebrafish embryo. Murine experiments revealed unexpected and complex
      bacterial population kinetics arising from clonal expansion during infection in
      particular organs. We subsequently elucidated the effect of antibiotic
      intervention within the host using mixed inocula of resistant and sensitive
      bacteria. Sub-curative tetracycline doses support the preferential expansion of
      resistant microorganisms, importantly unrelated to effects on growth rate or de
      novo resistance acquisition. This novel phenomenon is generic, occurring with
      methicillin-resistant S. aureus (MRSA) in the presence of beta-lactams and with
      the unrelated human pathogen Pseudomonas aeruginosa. The selection of resistant
      clones at low antibiotic levels can result in a rapid increase in their
      prevalence under conditions that would previously not be thought to favor them.
      Our results have key implications for the design of effective treatment regimes
      to limit the spread of antimicrobial resistance, where inappropriate usage
      leading to resistance may reduce the efficacy of life-saving drugs. 

PMID- 24586164
TI  - Epstein-Barr virus large tegument protein BPLF1 contributes to innate immune
      evasion through interference with toll-like receptor signaling.
AB  - Viral infection triggers an early host response through activation of pattern
      recognition receptors, including Toll-like receptors (TLR). TLR signaling
      cascades induce production of type I interferons and proinflammatory cytokines
      involved in establishing an anti-viral state as well as in orchestrating ensuing
      adaptive immunity. To allow infection, replication, and persistence,
      (herpes)viruses employ ingenious strategies to evade host immunity. The human
      gamma-herpesvirus Epstein-Barr virus (EBV) is a large, enveloped DNA virus
      persistently carried by more than 90% of adults worldwide. It is the causative
      agent of infectious mononucleosis and is associated with several malignant
      tumors. EBV activates TLRs, including TLR2, TLR3, and TLR9. Interestingly, both
      the expression of and signaling by TLRs is attenuated during productive EBV
      infection. Ubiquitination plays an important role in regulating TLR signaling and
      is controlled by ubiquitin ligases and deubiquitinases (DUBs). The EBV genome
      encodes three proteins reported to exert in vitro deubiquitinase activity. Using
      active site-directed probes, we show that one of these putative DUBs, the
      conserved herpesvirus large tegument protein BPLF1, acts as a functional DUB in
      EBV-producing B cells. The BPLF1 enzyme is expressed during the late phase of
      lytic EBV infection and is incorporated into viral particles. The N-terminal part
      of the large BPLF1 protein contains the catalytic site for DUB activity and
      suppresses TLR-mediated activation of NF-kappaB at, or downstream of, the TRAF6
      signaling intermediate. A catalytically inactive mutant of this EBV protein did
      not reduce NF-kappaB activation, indicating that DUB activity is essential for
      attenuating TLR signal transduction. Our combined results show that EBV employs
      deubiquitination of signaling intermediates in the TLR cascade as a mechanism to
      counteract innate anti-viral immunity of infected hosts. 

PMID- 24586166
TI  - MicroRNA editing facilitates immune elimination of HCMV infected cells.
AB  - The human cytomegalovirus (HCMV) is extremely prevalent in the human population.
      Infection by HCMV is life threatening in immune compromised individuals and in
      immune competent individuals it can cause severe birth defects, developmental
      retardation and is even associated with tumor development. While numerous
      mechanisms were developed by HCMV to interfere with immune cell activity, much
      less is known about cellular mechanisms that operate in response to HCMV
      infection. Here we demonstrate that in response to HCMV infection, the expression
      of the short form of the RNA editing enzyme ADAR1 (ADAR1-p110) is induced. We
      identified the specific promoter region responsible for this induction and we
      show that ADAR1-p110 can edit miR-376a. Accordingly, we demonstrate that the
      levels of the edited-miR-376a (miR-376a(e)) increase during HCMV infection.
      Importantly, we show that miR-376a(e) downregulates the immune modulating
      molecule HLA-E and that this consequently renders HCMV infected cells susceptible
      to elimination by NK cells. 

PMID- 24586167
TI  - Domain shuffling in a sensor protein contributed to the evolution of insect
      pathogenicity in plant-beneficial Pseudomonas protegens.
AB  - Pseudomonas protegens is a biocontrol rhizobacterium with a plant-beneficial and
      an insect pathogenic lifestyle, but it is not understood how the organism
      switches between the two states. Here, we focus on understanding the function and
      possible evolution of a molecular sensor that enables P. protegens to detect the
      insect environment and produce a potent insecticidal toxin specifically during
      insect infection but not on roots. By using quantitative single cell microscopy
      and mutant analysis, we provide evidence that the sensor histidine kinase FitF is
      a key regulator of insecticidal toxin production. Our experimental data and
      bioinformatic analyses indicate that FitF shares a sensing domain with DctB, a
      histidine kinase regulating carbon uptake in Proteobacteria. This suggested that
      FitF has acquired its specificity through domain shuffling from a common
      ancestor. We constructed a chimeric DctB-FitF protein and showed that it is
      indeed functional in regulating toxin expression in P. protegens. The shuffling
      event and subsequent adaptive modifications of the recruited sensor domain were
      critical for the microorganism to express its potent insect toxin in the observed
      host-specific manner. Inhibition of the FitF sensor during root colonization
      could explain the mechanism by which P. protegens differentiates between the
      plant and insect host. Our study establishes FitF of P. protegens as a prime
      model for molecular evolution of sensor proteins and bacterial pathogenicity. 

PMID- 24586165
TI  - Reversible silencing of cytomegalovirus genomes by type I interferon governs
      virus latency.
AB  - Herpesviruses establish a lifelong latent infection posing the risk for virus
      reactivation and disease. In cytomegalovirus infection, expression of the major
      immediate early (IE) genes is a critical checkpoint, driving the lytic
      replication cycle upon primary infection or reactivation from latency. While it
      is known that type I interferon (IFN) limits lytic CMV replication, its role in
      latency and reactivation has not been explored. In the model of mouse CMV
      infection, we show here that IFNbeta blocks mouse CMV replication at the level of
      IE transcription in IFN-responding endothelial cells and fibroblasts. The IFN
      mediated inhibition of IE genes was entirely reversible, arguing that the IFN
      effect may be consistent with viral latency. Importantly, the response to IFNbeta
      is stochastic, and MCMV IE transcription and replication were repressed only in
      IFN-responsive cells, while the IFN-unresponsive cells remained permissive for
      lytic MCMV infection. IFN blocked the viral lytic replication cycle by
      upregulating the nuclear domain 10 (ND10) components, PML, Sp100 and Daxx, and
      their knockdown by shRNA rescued viral replication in the presence of IFNbeta.
      Finally, IFNbeta prevented MCMV reactivation from endothelial cells derived from
      latently infected mice, validating our results in a biologically relevant
      setting. Therefore, our data do not only define for the first time the molecular
      mechanism of IFN-mediated control of CMV infection, but also indicate that the
      reversible inhibition of the virus lytic cycle by IFNbeta is consistent with the
      establishment of CMV latency. 

PMID- 24586169
TI  - A cyclophilin homology domain-independent role for Nup358 in HIV-1 infection.
AB  - The large nucleoporin Nup358/RanBP2 forms eight filaments that project from the
      nuclear pore into the cytoplasm where they function as docking platforms for
      nucleocytoplasmic transport receptors. RNAi screens have implicated Nup358 in the
      HIV-1 life cycle. The 164 C-terminal amino acids of this 3,224 amino acid protein
      are a cyclophilin homology domain (Nup358Cyp), which has potential to bind the
      HIV-1 capsid and regulate viral progress to integration. Here we examined the
      virological role of Nup358 in conditional knockout mouse cells and in RNAi
      depleted human CD4+ T cells. Cre-mediated gene knockout was toxic and diminished
      HIV-1 infectivity. However, cellular health and HIV-1 susceptibility were
      coordinately preserved if, prior to gene inactivation, a transposon was used to
      express all of Nup358 or only the N-terminal 1340 amino acids that contain three
      FG repeats and a Ran-binding domain. HIV-1, but not N74D capsid-mutant HIV-1, was
      markedly sensitive to TNPO3 depletion, but they infected 1-1340 segment
      complemented Nup358 knockout cells equivalently. Human and mouse CypA both
      rescued HIV-1 in CypA gene-/- Jurkat cells and TRIM-Nup358Cyp fusions derived
      from each species were equally antiviral; each also inhibited both WT and N74D
      virus. In the human CD4+T cell line SupT1, abrupt Nup358 depletion reduced viral
      replication but stable Nup358-depleted cells replicated HIV-1 normally. Thus,
      human CD4+ T cells can accommodate to loss of Nup358 and preserve HIV-1
      susceptibility. Experiments with cylosporine, viruses with capsids that do not
      bind cyclophilins, and growth arrest did not uncover viral dependency on the C
      terminal domains of Nup358. Our data reinforce the virological importance of
      TNPO3 and show that Nup358 supports nuclear transport functions important for
      cellular homeostasis and for HIV-1 nuclear import. However, the results do not
      suggest direct roles for the Nup358 cyclophilin or SUMO E3 ligase domains in
      engaging the HIV-1 capsid prior to nuclear translocation.

PMID- 24586168
TI  - Insights into the initiation of JC virus DNA replication derived from the crystal
      structure of the T-antigen origin binding domain.
AB  - JC virus is a member of the Polyomavirus family of DNA tumor viruses and the
      causative agent of progressive multifocal leukoencephalopathy (PML). PML is a
      disease that occurs primarily in people who are immunocompromised and is usually
      fatal. As with other Polyomavirus family members, the replication of JC virus
      (JCV) DNA is dependent upon the virally encoded protein T-antigen. To further our
      understanding of JCV replication, we have determined the crystal structure of the
      origin-binding domain (OBD) of JCV T-antigen. This structure provides the first
      molecular understanding of JCV T-ag replication functions; for example, it
      suggests how the JCV T-ag OBD site-specifically binds to the major groove of
      GAGGC sequences in the origin. Furthermore, these studies suggest how the JCV
      OBDs interact during subsequent oligomerization events. We also report that the
      OBD contains a novel "pocket"; which sequesters the A1 & B2 loops of neighboring
      molecules. Mutagenesis of a residue in the pocket associated with the JCV T-ag
      OBD interfered with viral replication. Finally, we report that relative to the
      SV40 OBD, the surface of the JCV OBD contains one hemisphere that is highly
      conserved and one that is highly variable. 

PMID- 24586170
TI  - Engagement of NKG2D on bystander memory CD8 T cells promotes increased
      immunopathology following Leishmania major infection.
AB  - One of the hallmarks of adaptive immunity is the development of a long-term
      pathogen specific memory response. While persistent memory T cells certainly
      impact the immune response during a secondary challenge, their role in unrelated
      infections is less clear. To address this issue, we utilized lymphocytic
      choriomeningitis virus (LCMV) and Listeria monocytogenes immune mice to
      investigate whether bystander memory T cells influence Leishmania major
      infection. Despite similar parasite burdens, LCMV and Listeria immune mice
      exhibited a significant increase in leishmanial lesion size compared to mice
      infected with L. major alone. This increased lesion size was due to a severe
      inflammatory response, consisting not only of monocytes and neutrophils, but also
      significantly more CD8 T cells. Many of the CD8 T cells were LCMV specific and
      expressed gzmB and NKG2D, but unexpectedly expressed very little IFN-gamma.
      Moreover, if CD8 T cells were depleted in LCMV immune mice prior to challenge
      with L. major, the increase in lesion size was lost. Strikingly, treating with
      NKG2D blocking antibodies abrogated the increased immunopathology observed in
      LCMV immune mice, showing that NKG2D engagement on LCMV specific memory CD8 T
      cells was required for the observed phenotype. These results indicate that
      bystander memory CD8 T cells can participate in an unrelated immune response and
      induce immunopathology through an NKG2D dependent mechanism without providing
      increased protection. 

PMID- 24586171
TI  - Code-assisted discovery of TAL effector targets in bacterial leaf streak of rice
      reveals contrast with bacterial blight and a novel susceptibility gene.
AB  - Bacterial leaf streak of rice, caused by Xanthomonas oryzae pv. oryzicola (Xoc)
      is an increasingly important yield constraint in this staple crop. A mesophyll
      colonizer, Xoc differs from X. oryzae pv. oryzae (Xoo), which invades xylem to
      cause bacterial blight of rice. Both produce multiple distinct TAL effectors,
      type III-delivered proteins that transactivate effector-specific host genes. A
      TAL effector finds its target(s) via a partially degenerate code whereby the
      modular effector amino acid sequence identifies nucleotide sequences to which the
      protein binds. Virulence contributions of some Xoo TAL effectors have been shown,
      and their relevant targets, susceptibility (S) genes, identified, but the role of
      TAL effectors in leaf streak is uncharacterized. We used host transcript
      profiling to compare leaf streak to blight and to probe functions of Xoc TAL
      effectors. We found that Xoc and Xoo induce almost completely different host
      transcriptional changes. Roughly one in three genes upregulated by the pathogens
      is preceded by a candidate TAL effector binding element. Experimental analysis of
      the 44 such genes predicted to be Xoc TAL effector targets verified nearly half,
      and identified most others as false predictions. None of the Xoc targets is a
      known bacterial blight S gene. Mutational analysis revealed that Tal2g, which
      activates two genes, contributes to lesion expansion and bacterial exudation. Use
      of designer TAL effectors discriminated a sulfate transporter gene as the S gene.
      Across all targets, basal expression tended to be higher than genome-average, and
      induction moderate. Finally, machine learning applied to real vs. falsely
      predicted targets yielded a classifier that recalled 92% of the real targets with
      88% precision, providing a tool for better target prediction in the future. Our
      study expands the number of known TAL effector targets, identifies a new class of
      S gene, and improves our ability to predict functional targeting. 

PMID- 24586173
TI  - The Epstein-Barr virus-encoded microRNA MiR-BART9 promotes tumor metastasis by
      targeting E-cadherin in nasopharyngeal carcinoma.
AB  - MicroRNAs (miRNAs) are a family of small RNA molecules that negatively regulate
      the expression of protein-coding genes and play critical roles in orchestrating
      diverse cellular processes. This regulatory mechanism is also exploited by
      viruses to direct their life cycle and evade the host immune system. Epstein-Barr
      virus (EBV) is an oncogenic virus that is closely associated with multiple human
      diseases, including nasopharyngeal carcinoma (NPC), which is a highly metastatic
      type of tumor and is frequently reported in South Asia. Several viral proteins
      have been found to promote the migration and invasiveness of NPC cells. However,
      not all tumor tissues express these viral oncoproteins, suggesting that other
      mechanisms may contribute to the aggressive behavior of NPC tumor cells. A
      previous sequencing study by our group revealed that the EBV miRNA miR-BART9 was
      expressed at high levels in all EBV-positive NPC tissues. In the present study,
      we used gain- and loss-of-function approaches to investigate the effect of miR
      BART9 in EBV-negative and EBV-positive NPC cells. We discovered that miR-BART9
      promotes the migration and invasiveness of cultured NPC cells. The promigratory
      activity observed in vitro was manifested as an enhanced metastatic ability in
      vivo. Computational analysis revealed that miR-BART9 may target E-cadherin, a
      membrane protein that is pivotal in preserving cell-cell junctions and the
      epithelial phenotype. Through biochemical assays and functional rescue analysis,
      we confirmed that miR-BART9 specifically inhibits E-cadherin to induce a
      mesenchymal-like phenotype and promote the migration of NPC cells. These results
      indicated that miR-BART9 is a prometastatic viral miRNA and suggested that high
      levels of miR-BART9 in EBV-positive NPC cells may contribute to the
      aggressiveness of tumor cells. 

PMID- 24586172
TI  - Structure of the membrane anchor of pestivirus glycoprotein E(rns), a long tilted
      amphipathic helix.
AB  - E(rns) is an essential virion glycoprotein with RNase activity that suppresses
      host cellular innate immune responses upon being partially secreted from the
      infected cells. Its unusual C-terminus plays multiple roles, as the amphiphilic
      helix acts as a membrane anchor, as a signal peptidase cleavage site, and as a
      retention/secretion signal. We analyzed the structure and membrane binding
      properties of this sequence to gain a better understanding of the underlying
      mechanisms. CD spectroscopy in different setups, as well as Monte Carlo and
      molecular dynamics simulations confirmed the helical folding and showed that the
      helix is accommodated in the amphiphilic region of the lipid bilayer with a
      slight tilt rather than lying parallel to the surface. This model was confirmed
      by NMR analyses that also identified a central stretch of 15 residues within the
      helix that is fully shielded from the aqueous layer, which is C-terminally
      followed by a putative hairpin structure. These findings explain the strong
      membrane binding of the protein and provide clues to establishing the E(rns)
      membrane contact, processing and secretion. 

PMID- 24586174
TI  - Implication of PMLIV in both intrinsic and innate immunity.
AB  - PML/TRIM19, the organizer of nuclear bodies (NBs), has been implicated in the
      antiviral response to diverse RNA and DNA viruses. Several PML isoforms generated
      from a single PML gene by alternative splicing, share the same N-terminal region
      containing the RBCC/tripartite motif but differ in their C-terminal sequences.
      Recent studies of all the PML isoforms reveal the specific functions of each. The
      knockout of PML renders mice more sensitive to vesicular stomatitis virus (VSV).
      Here we report that among PML isoforms (PMLI to PMLVIIb), only PMLIII and PMLIV
      confer resistance to VSV. Unlike PMLIII, whose anti-VSV activity is IFN
      independent, PMLIV can act at two stages: it confers viral resistance directly in
      an IFN-independent manner and also specifically enhances IFN-beta production via
      a higher activation of IRF3, thus protecting yet uninfected cells from oncoming
      infection. PMLIV SUMOylation is required for both activities. This demonstrates
      for the first time that PMLIV is implicated in innate immune response through
      enhanced IFN-beta synthesis. Depletion of IRF3 further demonstrates the dual
      activity of PMLIV, since it abrogated PMLIV-induced IFN synthesis but not PMLIV
      induced inhibition of viral proteins. Mechanistically, PMLIV enhances IFN-beta
      synthesis by regulating the cellular distribution of Pin1 (peptidyl-prolyl
      cis/trans isomerase), inducing its recruitment to PML NBs where both proteins
      colocalize. The interaction of SUMOylated PMLIV with endogenous Pin1 and its
      recruitment within PML NBs prevents the degradation of activated IRF3, and thus
      potentiates IRF3-dependent production of IFN-beta. Whereas the intrinsic
      antiviral activity of PMLIV is specific to VSV, its effect on IFN-beta synthesis
      is much broader, since it affects a key actor of innate immune pathways. Our
      results show that, in addition to its intrinsic anti-VSV activity, PMLIV
      positively regulates IFN-beta synthesis in response to different inducers, thus
      adding PML/TRIM19 to the growing list of TRIM proteins implicated in both
      intrinsic and innate immunity. 

PMID- 24586175
TI  - Human genome-wide RNAi screen identifies an essential role for inositol
      pyrophosphates in Type-I interferon response.
AB  - The pattern recognition receptor RIG-I is critical for Type-I interferon
      production. However, the global regulation of RIG-I signaling is only partially
      understood. Using a human genome-wide RNAi-screen, we identified 226 novel
      regulatory proteins of RIG-I mediated interferon-beta production. Furthermore,
      the screen identified a metabolic pathway that synthesizes the inositol
      pyrophosphate 1-IP7 as a previously unrecognized positive regulator of interferon
      production. Detailed genetic and biochemical experiments demonstrated that the
      kinase activities of IPPK, PPIP5K1 and PPIP5K2 (which convert IP5 to1-IP7) were
      critical for both interferon induction, and the control of cellular infection by
      Sendai and influenza A viruses. Conversely, ectopically expressed inositol
      pyrophosphate-hydrolases DIPPs attenuated interferon transcription. Mechanistic
      experiments in intact cells revealed that the expression of IPPK, PPIP5K1 and
      PPIP5K2 was needed for the phosphorylation and activation of IRF3, a
      transcription factor for interferon. The addition of purified individual inositol
      pyrophosphates to a cell free reconstituted RIG-I signaling assay further
      identified 1-IP7 as an essential component required for IRF3 activation. The
      inositol pyrophosphate may act by beta-phosphoryl transfer, since its action was
      not recapitulated by a synthetic phosphonoacetate analogue of 1-IP7. This study
      thus identified several novel regulators of RIG-I, and a new role for inositol
      pyrophosphates in augmenting innate immune responses to viral infection that may
      have therapeutic applications. 

PMID- 24586176
TI  - Highly active antiretroviral therapies are effective against HIV-1 cell-to-cell
      transmission.
AB  - HIV-1 cell-to-cell transmission allows for 2-3 orders of magnitude more efficient
      viral spread than cell-free dissemination. The high local multiplicity of
      infection (MOI) observed at cell-cell contact sites may lower the efficacy of
      antiretroviral therapies (ART). Here we test the efficacy of commonly used
      antiretroviral inhibitors against cell-to-cell and cell-free HIV-1 transmission.
      We demonstrate that, while some nucleoside-analog reverse transcriptase
      inhibitors (NRTI) are less effective against HIV-1 cell-to-cell transmission,
      most non-nucleoside-analog reverse transcriptase inhibitors (NNRTI), entry
      inhibitors and protease inhibitors remain highly effective. Moreover, poor NRTIs
      become highly effective when applied in combinations explaining the effectiveness
      of ART in clinical settings. Investigating the underlying mechanism, we observe a
      strict correlation between the ability of individual drugs and combinations of
      drugs to interfere with HIV-1 cell-to-cell transmission, and their effectiveness
      against high viral MOIs. Our results suggest that the ability to suppress high
      viral MOI is a feature of effective ART regimens and this parameter should be
      considered when designing novel antiviral therapies. 

PMID- 24586177
TI  - CEP-1, the Caenorhabditis elegans p53 homolog, mediates opposing longevity
      outcomes in mitochondrial electron transport chain mutants.
AB  - Caenorhabditis elegans CEP-1 and its mammalian homolog p53 are critical for
      responding to diverse stress signals. In this study, we found that cep-1
      inactivation suppressed the prolonged lifespan of electron transport chain (ETC)
      mutants, such as isp-1 and nuo-6, but rescued the shortened lifespan of other ETC
      mutants, such as mev-1 and gas-1. We compared the CEP-1-regulated transcriptional
      profiles of the long-lived isp-1 and the short-lived mev-1 mutants and, to our
      surprise, found that CEP-1 regulated largely similar sets of target genes in the
      two mutants despite exerting opposing effects on their longevity. Further
      analyses identified a small subset of CEP-1-regulated genes that displayed
      distinct expression changes between the isp-1 and mev-1 mutants. Interestingly,
      this small group of differentially regulated genes are enriched for the "aging"
      Gene Ontology term, consistent with the hypothesis that they might be
      particularly important for mediating the distinct longevity effects of CEP-1 in
      isp-1 and mev-1 mutants. We further focused on one of these differentially
      regulated genes, ftn-1, which encodes ferritin in C. elegans, and demonstrated
      that it specifically contributed to the extended lifespan of isp-1 mutant worms
      but did not affect the mev-1 mutant lifespan. We propose that CEP-1 responds to
      different mitochondrial ETC stress by mounting distinct compensatory responses
      accordingly to modulate animal physiology and longevity. Our findings provide
      insights into how mammalian p53 might respond to distinct mitochondrial stressors
      to influence cellular and organismal responses. 

PMID- 24586178
TI  - Analysis of meiosis in SUN1 deficient mice reveals a distinct role of SUN2 in
      mammalian meiotic LINC complex formation and function.
AB  - LINC complexes are evolutionarily conserved nuclear envelope bridges, composed of
      SUN (Sad-1/UNC-84) and KASH (Klarsicht/ANC-1/Syne/homology) domain proteins. They
      are crucial for nuclear positioning and nuclear shape determination, and also
      mediate nuclear envelope (NE) attachment of meiotic telomeres, essential for
      driving homolog synapsis and recombination. In mice, SUN1 and SUN2 are the only
      SUN domain proteins expressed during meiosis, sharing their localization with
      meiosis-specific KASH5. Recent studies have shown that loss of SUN1 severely
      interferes with meiotic processes. Absence of SUN1 provokes defective telomere
      attachment and causes infertility. Here, we report that meiotic telomere
      attachment is not entirely lost in mice deficient for SUN1, but numerous
      telomeres are still attached to the NE through SUN2/KASH5-LINC complexes. In
      Sun1(-/-) meiocytes attached telomeres retained the capacity to form bouquet-like
      clusters. Furthermore, we could detect significant numbers of late meiotic
      recombination events in Sun1(-/-) mice. Together, this indicates that even in the
      absence of SUN1 telomere attachment and their movement within the nuclear
      envelope per se can be functional. 

PMID- 24586179
TI  - Targeted ablation of nesprin 1 and nesprin 2 from murine myocardium results in
      cardiomyopathy, altered nuclear morphology and inhibition of the biomechanical
      gene response.
AB  - Recent interest has focused on the importance of the nucleus and associated
      nucleoskeleton in regulating changes in cardiac gene expression in response to
      biomechanical load. Mutations in genes encoding proteins of the inner nuclear
      membrane and nucleoskeleton, which cause cardiomyopathy, also disrupt expression
      of a biomechanically responsive gene program. Furthermore, mutations in the outer
      nuclear membrane protein Nesprin 1 and 2 have been implicated in cardiomyopathy.
      Here, we identify for the first time a role for the outer nuclear membrane
      proteins, Nesprin 1 and Nesprin 2, in regulating gene expression in response to
      biomechanical load. Ablation of both Nesprin 1 and 2 in cardiomyocytes, but
      neither alone, resulted in early onset cardiomyopathy. Mutant cardiomyocytes
      exhibited altered nuclear positioning, shape, and chromatin positioning. Loss of
      Nesprin 1 or 2, or both, led to impairment of gene expression changes in response
      to biomechanical stimuli. These data suggest a model whereby biomechanical
      signals are communicated from proteins of the outer nuclear membrane, to the
      inner nuclear membrane and nucleoskeleton, to result in changes in gene
      expression required for adaptation of the cardiomyocyte to changes in
      biomechanical load, and give insights into etiologies underlying cardiomyopathy
      consequent to mutations in Nesprin 1 and 2. 

PMID- 24586180
TI  - Loss of Trabid, a new negative regulator of the drosophila immune-deficiency
      pathway at the level of TAK1, reduces life span.
AB  - A relatively unexplored nexus in Drosophila Immune deficiency (IMD) pathway is
      TGF-beta Activating Kinase 1 (TAK1), which triggers both immunity and apoptosis.
      In a cell culture screen, we identified that Lysine at position 142 was a K63
      linked Ubiquitin acceptor site for TAK1, required for signalling. Moreover,
      Lysine at position 156 functioned as a K48-linked Ubiquitin acceptor site, also
      necessary for TAK1 activity. The deubiquitinase Trabid interacted with TAK1,
      reducing immune signalling output and K63-linked ubiquitination. The three tandem
      Npl4 Zinc Fingers and the catalytic Cysteine at position 518 were required for
      Trabid activity. Flies deficient for Trabid had a reduced life span due to
      chronic activation of IMD both systemically as well as in their gut where
      homeostasis was disrupted. The TAK1-associated Binding Protein 2 (TAB2) was
      linked with the TAK1-Trabid interaction through its Zinc finger domain that
      pacified the TAK1 signal. These results indicate an elaborate and multi-tiered
      mechanism for regulating TAK1 activity and modulating its immune signal. 

PMID- 24586181
TI  - Cascades of genetic instability resulting from compromised break-induced
      replication.
AB  - Break-induced replication (BIR) is a mechanism to repair double-strand breaks
      (DSBs) that possess only a single end that can find homology in the genome. This
      situation can result from the collapse of replication forks or telomere erosion.
      BIR frequently produces various genetic instabilities including mutations, loss
      of heterozygosity, deletions, duplications, and template switching that can
      result in copy-number variations (CNVs). An important type of genomic
      rearrangement specifically linked to BIR is half-crossovers (HCs), which result
      from fusions between parts of recombining chromosomes. Because HC formation
      produces a fused molecule as well as a broken chromosome fragment, these events
      could be highly destabilizing. Here we demonstrate that HC formation results from
      the interruption of BIR caused by a damaged template, defective replisome or
      premature onset of mitosis. Additionally, we document that checkpoint failure
      promotes channeling of BIR into half-crossover-initiated instability cascades
      (HCC) that resemble cycles of non-reciprocal translocations (NRTs) previously
      described in human tumors. We postulate that HCs represent a potent source of
      genetic destabilization with significant consequences that mimic those observed
      in human diseases, including cancer. 

PMID- 24586182
TI  - Quantitative genome-wide genetic interaction screens reveal global epistatic
      relationships of protein complexes in Escherichia coli.
AB  - Large-scale proteomic analyses in Escherichia coli have documented the
      composition and physical relationships of multiprotein complexes, but not their
      functional organization into biological pathways and processes. Conversely,
      genetic interaction (GI) screens can provide insights into the biological role(s)
      of individual gene and higher order associations. Combining the information from
      both approaches should elucidate how complexes and pathways intersect
      functionally at a systems level. However, such integrative analysis has been
      hindered due to the lack of relevant GI data. Here we present a systematic,
      unbiased, and quantitative synthetic genetic array screen in E. coli describing
      the genetic dependencies and functional cross-talk among over 600,000 digenic
      mutant combinations. Combining this epistasis information with putative
      functional modules derived from previous proteomic data and genomic context-based
      methods revealed unexpected associations, including new components required for
      the biogenesis of iron-sulphur and ribosome integrity, and the interplay between
      molecular chaperones and proteases. We find that functionally-linked genes co
      conserved among gamma-proteobacteria are far more likely to have correlated GI
      profiles than genes with divergent patterns of evolution. Overall, examining
      bacterial GIs in the context of protein complexes provides avenues for a deeper
      mechanistic understanding of core microbial systems. 

PMID- 24586184
TI  - Extreme population differences in the human zinc transporter ZIP4 (SLC39A4) are
      explained by positive selection in Sub-Saharan Africa.
AB  - Extreme differences in allele frequency between West Africans and Eurasians were
      observed for a leucine-to-valine substitution (Leu372Val) in the human intestinal
      zinc uptake transporter, ZIP4, yet no further evidence was found for a selective
      sweep around the ZIP4 gene (SLC39A4). By interrogating allele frequencies in more
      than 100 diverse human populations and resequencing Neanderthal DNA, we confirmed
      the ancestral state of this locus and found a strong geographical gradient for
      the derived allele (Val372), with near fixation in West Africa. In extensive
      coalescent simulations, we show that the extreme differences in allele frequency,
      yet absence of a classical sweep signature, can be explained by the effect of a
      local recombination hotspot, together with directional selection favoring the
      Val372 allele in Sub-Saharan Africans. The possible functional effect of the
      Leu372Val substitution, together with two pathological mutations at the same
      codon (Leu372Pro and Leu372Arg) that cause acrodermatitis enteropathica (a
      disease phenotype characterized by extreme zinc deficiency), was investigated by
      transient overexpression of human ZIP4 protein in HeLa cells. Both acrodermatitis
      mutations cause absence of the ZIP4 transporter cell surface expression and
      nearly absent zinc uptake, while the Val372 variant displayed significantly
      reduced surface protein expression, reduced basal levels of intracellular zinc,
      and reduced zinc uptake in comparison with the Leu372 variant. We speculate that
      reduced zinc uptake by the ZIP4-derived Val372 isoform may act by starving
      certain pathogens of zinc, and hence may have been advantageous in Sub-Saharan
      Africa. Moreover, these functional results may indicate differences in zinc
      homeostasis among modern human populations with possible relevance for disease
      risk. 

PMID- 24586185
TI  - Chk2 and p53 regulate the transmission of healed chromosomes in the Drosophila
      male germline.
AB  - When a dicentric chromosome breaks in mitosis, the broken ends cannot be repaired
      by normal mechanisms that join two broken ends since each end is in a separate
      daughter cell. However, in the male germline of Drosophila melanogaster, a broken
      end may be healed by de novo telomere addition. We find that Chk2 (encoded by
      lok) and P53, major mediators of the DNA damage response, have strong and
      opposite influences on the transmission of broken-and-healed chromosomes: lok
      mutants exhibit a large increase in the recovery of healed chromosomes relative
      to wildtype control males, but p53 mutants show a strong reduction. This
      contrasts with the soma, where mutations in lok and p53 have the nearly identical
      effect of allowing survival and proliferation of cells with irreparable DNA
      damage. Examination of testes revealed a transient depletion of germline cells
      after dicentric chromosome induction in the wildtype controls, and further showed
      that P53 is required for the germline to recover. Although lok mutant males
      transmit healed chromosomes at a high rate, broken chromosome ends can also
      persist through spermatogonial divisions without healing in lok mutants, giving
      rise to frequent dicentric bridges in Meiosis II. Cytological and genetic
      analyses show that spermatid nuclei derived from such meiotic divisions are
      eliminated during spermiogenesis, resulting in strong meiotic drive. We conclude
      that the primary responsibility for maintaining genome integrity in the male
      germline lies with Chk2, and that P53 is required to reconstitute the germline
      when cells are eliminated owing to unrepaired DNA damage. 

PMID- 24586186
TI  - Genome-wide association study of metabolic traits reveals novel gene-metabolite
      disease links.
AB  - Metabolic traits are molecular phenotypes that can drive clinical phenotypes and
      may predict disease progression. Here, we report results from a metabolome- and
      genome-wide association study on (1)H-NMR urine metabolic profiles. The study was
      conducted within an untargeted approach, employing a novel method for compound
      identification. From our discovery cohort of 835 Caucasian individuals who
      participated in the CoLaus study, we identified 139 suggestively significant
      (P<5*10(-8)) and independent associations between single nucleotide polymorphisms
      (SNP) and metabolome features. Fifty-six of these associations replicated in the
      TasteSensomics cohort, comprising 601 individuals from Sao Paulo of vastly
      diverse ethnic background. They correspond to eleven gene-metabolite
      associations, six of which had been previously identified in the urine metabolome
      and three in the serum metabolome. Our key novel findings are the associations of
      two SNPs with NMR spectral signatures pointing to fucose (rs492602, P = 6.9*10(
      44)) and lysine (rs8101881, P = 1.2*10(-33)), respectively. Fine-mapping of the
      first locus pinpointed the FUT2 gene, which encodes a fucosyltransferase enzyme
      and has previously been associated with Crohn's disease. This implicates fucose
      as a potential prognostic disease marker, for which there is already published
      evidence from a mouse model. The second SNP lies within the SLC7A9 gene, rare
      mutations of which have been linked to severe kidney damage. The replication of
      previous associations and our new discoveries demonstrate the potential of
      untargeted metabolomics GWAS to robustly identify molecular disease markers. 

PMID- 24586187
TI  - Ddc2 mediates Mec1 activation through a Ddc1- or Dpb11-independent mechanism.
AB  - The protein kinase Mec1 (ATR ortholog) and its partner Ddc2 (ATRIP ortholog) play
      a key role in DNA damage checkpoint responses in budding yeast. Previous studies
      have established the model in which Ddc1, a subunit of the checkpoint clamp, and
      Dpb11, related to TopBP1, activate Mec1 directly and control DNA damage
      checkpoint responses at G1 and G2/M. In this study, we show that Ddc2 contributes
      to Mec1 activation through a Ddc1- or Dpb11-independent mechanism. The catalytic
      activity of Mec1 increases after DNA damage in a Ddc2-dependent manner. In
      contrast, Mec1 activation occurs even in the absence of Ddc1 and Dpb11 function
      at G2/M. Ddc2 recruits Mec1 to sites of DNA damage. To dissect the role of Ddc2
      in Mec1 activation, we isolated and characterized a separation-of-function
      mutation in DDC2, called ddc2-S4. The ddc2-S4 mutation does not affect Mec1
      recruitment but diminishes Mec1 activation. Mec1 phosphorylates histone H2A in
      response to DNA damage. The ddc2-S4 mutation decreases phosphorylation of histone
      H2A more significantly than the absence of Ddc1 and Dpb11 function does. Our
      results suggest that Ddc2 plays a critical role in Mec1 activation as well as
      Mec1 localization at sites of DNA damage. 

PMID- 24586188
TI  - Serine carboxypeptidase SCPEP1 and Cathepsin A play complementary roles in
      regulation of vasoconstriction via inactivation of endothelin-1.
AB  - The potent vasoconstrictor peptides, endothelin 1 (ET-1) and angiotensin II
      control adaptation of blood vessels to fluctuations of blood pressure. Previously
      we have shown that the circulating level of ET-1 is regulated through its
      proteolytic cleavage by secreted serine carboxypeptidase, cathepsin A (CathA).
      However, genetically-modified mouse expressing catalytically inactive CathA S190A
      mutant retained about 10-15% of the carboxypeptidase activity against ET-1 in its
      tissues suggesting a presence of parallel/redundant catabolic pathway(s). In the
      current work we provide direct evidence that the enzyme, which complements CathA
      action towards ET-1 is a retinoid-inducible lysosomal serine carboxypeptidase 1
      (Scpep1), a CathA homolog with previously unknown biological function. We
      generated a mouse strain devoid of both CathA and Scpep1 activities (DD mice) and
      found that in response to high-salt diet and systemic injections of ET-1 these
      animals showed significantly increased blood pressure as compared to wild type
      mice or those with single deficiencies of CathA or Scpep1. We also found that the
      reactivity of mesenteric arteries from DD mice towards ET-1 was significantly
      higher than that for all other groups of mice. The DD mice had a reduced
      degradation rate of ET-1 in the blood whereas their cultured arterial vascular
      smooth muscle cells showed increased ET-1-dependent phosphorylation of myosin
      light chain 2. Together, our results define the biological role of mammalian
      serine carboxypeptidase Scpep1 and suggest that Scpep1 and CathA together
      participate in the control of ET-1 regulation of vascular tone and hemodynamics. 

PMID- 24586183
TI  - Identification of novel genetic Loci associated with thyroid peroxidase
      antibodies and clinical thyroid disease.
AB  - Autoimmune thyroid diseases (AITD) are common, affecting 2-5% of the general
      population. Individuals with positive thyroid peroxidase antibodies (TPOAbs) have
      an increased risk of autoimmune hypothyroidism (Hashimoto's thyroiditis), as well
      as autoimmune hyperthyroidism (Graves' disease). As the possible causative genes
      of TPOAbs and AITD remain largely unknown, we performed GWAS meta-analyses in
      18,297 individuals for TPOAb-positivity (1769 TPOAb-positives and 16,528 TPOAb
      negatives) and in 12,353 individuals for TPOAb serum levels, with replication in
      8,990 individuals. Significant associations (P<5*10(-8)) were detected at TPO
      rs11675434, ATXN2-rs653178, and BACH2-rs10944479 for TPOAb-positivity, and at TPO
      rs11675434, MAGI3-rs1230666, and KALRN-rs2010099 for TPOAb levels. Individual and
      combined effects (genetic risk scores) of these variants on (subclinical) hypo-
      and hyperthyroidism, goiter and thyroid cancer were studied. Individuals with a
      high genetic risk score had, besides an increased risk of TPOAb-positivity (OR:
      2.18, 95% CI 1.68-2.81, P = 8.1*10(-8)), a higher risk of increased thyroid
      stimulating hormone levels (OR: 1.51, 95% CI 1.26-1.82, P = 2.9*10(-6)), as well
      as a decreased risk of goiter (OR: 0.77, 95% CI 0.66-0.89, P = 6.5*10(-4)). The
      MAGI3 and BACH2 variants were associated with an increased risk of
      hyperthyroidism, which was replicated in an independent cohort of patients with
      Graves' disease (OR: 1.37, 95% CI 1.22-1.54, P = 1.2*10(-7) and OR: 1.25, 95% CI
      1.12-1.39, P = 6.2*10(-5)). The MAGI3 variant was also associated with an
      increased risk of hypothyroidism (OR: 1.57, 95% CI 1.18-2.10, P = 1.9*10(-3)).
      This first GWAS meta-analysis for TPOAbs identified five newly associated loci,
      three of which were also associated with clinical thyroid disease. With these
      markers we identified a large subgroup in the general population with a
      substantially increased risk of TPOAbs. The results provide insight into why
      individuals with thyroid autoimmunity do or do not eventually develop thyroid
      disease, and these markers may therefore predict which TPOAb-positives are
      particularly at risk of developing clinical thyroid dysfunction. 

PMID- 24586189
TI  - Classic selective sweeps revealed by massive sequencing in cattle.
AB  - Human driven selection during domestication and subsequent breed formation has
      likely left detectable signatures within the genome of modern cattle. The
      elucidation of these signatures of selection is of interest from the perspective
      of evolutionary biology, and for identifying domestication-related genes that
      ultimately may help to further genetically improve this economically important
      animal. To this end, we employed a panel of more than 15 million autosomal SNPs
      identified from re-sequencing of 43 Fleckvieh animals. We mainly applied two
      somewhat complementary statistics, the integrated Haplotype Homozygosity Score
      (iHS) reflecting primarily ongoing selection, and the Composite of Likelihood
      Ratio (CLR) having the most power to detect completed selection after fixation of
      the advantageous allele. We find 106 candidate selection regions, many of which
      are harboring genes related to phenotypes relevant in domestication, such as coat
      coloring pattern, neurobehavioral functioning and sensory perception including
      KIT, MITF, MC1R, NRG4, Erbb4, TMEM132D and TAS2R16, among others. To further
      investigate the relationship between genes with signatures of selection and genes
      identified in QTL mapping studies, we use a sample of 3062 animals to perform
      four genome-wide association analyses using appearance traits, body size and
      somatic cell count. We show that regions associated with coat coloring
      significantly (P<0.0001) overlap with the candidate selection regions, suggesting
      that the selection signals we identify are associated with traits known to be
      affected by selection during domestication. Results also provide further evidence
      regarding the complexity of the genetics underlying coat coloring in cattle. This
      study illustrates the potential of population genetic approaches for identifying
      genomic regions affecting domestication-related phenotypes and further helps to
      identify specific regions targeted by selection during speciation, domestication
      and breed formation of cattle. We also show that Linkage Disequilibrium (LD)
      decays in cattle at a much faster rate than previously thought. 

PMID- 24586190
TI  - Mapping the fitness landscape of gene expression uncovers the cause of antagonism
      and sign epistasis between adaptive mutations.
AB  - How do adapting populations navigate the tensions between the costs of gene
      expression and the benefits of gene products to optimize the levels of many genes
      at once? Here we combined independently-arising beneficial mutations that altered
      enzyme levels in the central metabolism of Methylobacterium extorquens to uncover
      the fitness landscape defined by gene expression levels. We found strong
      antagonism and sign epistasis between these beneficial mutations. Mutations with
      the largest individual benefit interacted the most antagonistically with other
      mutations, a trend we also uncovered through analyses of datasets from other
      model systems. However, these beneficial mutations interacted multiplicatively
      (i.e., no epistasis) at the level of enzyme expression. By generating a model
      that predicts fitness from enzyme levels we could explain the observed sign
      epistasis as a result of overshooting the optimum defined by a balance between
      enzyme catalysis benefits and fitness costs. Knowledge of the phenotypic
      landscape also illuminated that, although the fitness peak was phenotypically far
      from the ancestral state, it was not genetically distant. Single beneficial
      mutations jumped straight toward the global optimum rather than being constrained
      to change the expression phenotypes in the correlated fashion expected by the
      genetic architecture. Given that adaptation in nature often results from
      optimizing gene expression, these conclusions can be widely applicable to other
      organisms and selective conditions. Poor interactions between individually
      beneficial alleles affecting gene expression may thus compromise the benefit of
      sex during adaptation and promote genetic differentiation. 

PMID- 24586191
TI  - Natural polymorphisms in Tap2 influence negative selection and CD4?CD8 lineage
      commitment in the rat.
AB  - Genetic variation in the major histocompatibility complex (MHC) affects CD4?CD8
      lineage commitment and MHC expression. However, the contribution of specific
      genes in this gene-dense region has not yet been resolved. Nor has it been
      established whether the same genes regulate MHC expression and T cell selection.
      Here, we assessed the impact of natural genetic variation on MHC expression and
      CD4?CD8 lineage commitment using two genetic models in the rat. First, we mapped
      Quantitative Trait Loci (QTLs) associated with variation in MHC class I and II
      protein expression and the CD4?CD8 T cell ratio in outbred Heterogeneous Stock
      rats. We identified 10 QTLs across the genome and found that QTLs for the
      individual traits colocalized within a region spanning the MHC. To identify the
      genes underlying these overlapping QTLs, we generated a large panel of MHC
      recombinant congenic strains, and refined the QTLs to two adjacent intervals of
      ~0.25 Mb in the MHC-I and II regions, respectively. An interaction between these
      intervals affected MHC class I expression as well as negative selection and
      lineage commitment of CD8 single-positive (SP) thymocytes. We mapped this effect
      to the transporter associated with antigen processing 2 (Tap2) in the MHC-II
      region and the classical MHC class I gene(s) (RT1-A) in the MHC-I region. This
      interaction was revealed by a recombination between RT1-A and Tap2, which
      occurred in 0.2% of the rats. Variants of Tap2 have previously been shown to
      influence the antigenicity of MHC class I molecules by altering the MHC class I
      ligandome. Our results show that a restricted peptide repertoire on MHC class I
      molecules leads to reduced negative selection of CD8SP cells. To our knowledge,
      this is the first study showing how a recombination between natural alleles of
      genes in the MHC influences lineage commitment of T cells. 

PMID- 24586192
TI  - Distinct requirements for cranial ectoderm and mesenchyme-derived wnts in
      specification and differentiation of osteoblast and dermal progenitors.
AB  - The cranial bones and dermis differentiate from mesenchyme beneath the surface
      ectoderm. Fate selection in cranial mesenchyme requires the canonical Wnt
      effector molecule beta-catenin, but the relative contribution of Wnt ligand
      sources in this process remains unknown. Here we show Wnt ligands are expressed
      in cranial surface ectoderm and underlying supraorbital mesenchyme during dermal
      and osteoblast fate selection. Using conditional genetics, we eliminate secretion
      of all Wnt ligands from cranial surface ectoderm or undifferentiated mesenchyme,
      to uncover distinct roles for ectoderm- and mesenchyme-derived Wnts. Ectoderm Wnt
      ligands induce osteoblast and dermal fibroblast progenitor specification while
      initiating expression of a subset of mesenchymal Wnts. Mesenchyme Wnt ligands are
      subsequently essential during differentiation of dermal and osteoblast
      progenitors. Finally, ectoderm-derived Wnt ligands provide an inductive cue to
      the cranial mesenchyme for the fate selection of dermal fibroblast and osteoblast
      lineages. Thus two sources of Wnt ligands perform distinct functions during
      osteoblast and dermal fibroblast formation. 

PMID- 24586193
TI  - A variant in the neuropeptide receptor npr-1 is a major determinant of
      Caenorhabditis elegans growth and physiology.
AB  - The mechanistic basis for how genetic variants cause differences in phenotypic
      traits is often elusive. We identified a quantitative trait locus in
      Caenorhabditis elegans that affects three seemingly unrelated phenotypic traits:
      lifetime fecundity, adult body size, and susceptibility to the human pathogen
      Staphyloccus aureus. We found a QTL for all three traits arises from variation in
      the neuropeptide receptor gene npr-1. Moreover, we found that variation in npr-1
      is also responsible for differences in 247 gene expression traits. Variation in
      npr-1 is known to determine whether animals disperse throughout a bacterial lawn
      or aggregate at the edges of the lawn. We found that the allele that leads to
      aggregation is associated with reduced growth and reproductive output. The
      altered gene expression pattern caused by this allele suggests that the
      aggregation behavior might cause a weak starvation state, which is known to
      reduce growth rate and fecundity. Importantly, we show that variation in npr-1
      causes each of these phenotypic differences through behavioral avoidance of
      ambient oxygen concentrations. These results suggest that variation in npr-1 has
      broad pleiotropic effects mediated by altered exposure to bacterial food. 

PMID- 24586194
TI  - Genomic networks of hybrid sterility.
AB  - Hybrid dysfunction, a common feature of reproductive barriers between species, is
      often caused by negative epistasis between loci ("Dobzhansky-Muller
      incompatibilities"). The nature and complexity of hybrid incompatibilities remain
      poorly understood because identifying interacting loci that affect complex
      phenotypes is difficult. With subspecies in the early stages of speciation, an
      array of genetic tools, and detailed knowledge of reproductive biology, house
      mice (Mus musculus) provide a model system for dissecting hybrid
      incompatibilities. Male hybrids between M. musculus subspecies often show reduced
      fertility. Previous studies identified loci and several X chromosome-autosome
      interactions that contribute to sterility. To characterize the genetic basis of
      hybrid sterility in detail, we used a systems genetics approach, integrating
      mapping of gene expression traits with sterility phenotypes and QTL. We measured
      genome-wide testis expression in 305 male F2s from a cross between wild-derived
      inbred strains of M. musculus musculus and M. m. domesticus. We identified
      several thousand cis- and trans-acting QTL contributing to expression variation
      (eQTL). Many trans eQTL cluster into eleven 'hotspots,' seven of which co
      localize with QTL for sterility phenotypes identified in the cross. The number
      and clustering of trans eQTL-but not cis eQTL-were substantially lower when
      mapping was restricted to a 'fertile' subset of mice, providing evidence that
      trans eQTL hotspots are related to sterility. Functional annotation of
      transcripts with eQTL provides insights into the biological processes disrupted
      by sterility loci and guides prioritization of candidate genes. Using a
      conditional mapping approach, we identified eQTL dependent on interactions
      between loci, revealing a complex system of epistasis. Our results illuminate
      established patterns, including the role of the X chromosome in hybrid sterility.
      The integrated mapping approach we employed is applicable in a broad range of
      organisms and we advocate for widespread adoption of a network-centered approach
      in speciation genetics. 

PMID- 24586195
TI  - Mammalian E-type cyclins control chromosome pairing, telomere stability and CDK2
      localization in male meiosis.
AB  - Loss of function of cyclin E1 or E2, important regulators of the mitotic cell
      cycle, yields viable mice, but E2-deficient males display reduced fertility. To
      elucidate the role of E-type cyclins during spermatogenesis, we characterized
      their expression patterns and produced additional deletions of Ccne1 and Ccne2
      alleles in the germline, revealing unexpected meiotic functions. While Ccne2 mRNA
      and protein are abundantly expressed in spermatocytes, Ccne1 mRNA is present but
      its protein is detected only at low levels. However, abundant levels of cyclin E1
      protein are detected in spermatocytes deficient in cyclin E2 protein. Additional
      depletion of E-type cyclins in the germline resulted in increasingly enhanced
      spermatogenic abnormalities and corresponding decreased fertility and loss of
      germ cells by apoptosis. Profound meiotic defects were observed in spermatocytes,
      including abnormal pairing and synapsis of homologous chromosomes, heterologous
      chromosome associations, unrepaired double-strand DNA breaks, disruptions in
      telomeric structure and defects in cyclin-dependent-kinase 2 localization. These
      results highlight a new role for E-type cyclins as important regulators of male
      meiosis. 

PMID- 24586196
TI  - DAAM is required for thin filament formation and Sarcomerogenesis during muscle
      development in Drosophila.
AB  - During muscle development, myosin and actin containing filaments assemble into
      the highly organized sarcomeric structure critical for muscle function. Although
      sarcomerogenesis clearly involves the de novo formation of actin filaments, this
      process remained poorly understood. Here we show that mouse and Drosophila
      members of the DAAM formin family are sarcomere-associated actin assembly factors
      enriched at the Z-disc and M-band. Analysis of dDAAM mutants revealed a pivotal
      role in myofibrillogenesis of larval somatic muscles, indirect flight muscles and
      the heart. We found that loss of dDAAM function results in multiple defects in
      sarcomere development including thin and thick filament disorganization, Z-disc
      and M-band formation, and a near complete absence of the myofibrillar lattice.
      Collectively, our data suggest that dDAAM is required for the initial assembly of
      thin filaments, and subsequently it promotes filament elongation by assembling
      short actin polymers that anneal to the pointed end of the growing filaments, and
      by antagonizing the capping protein Tropomodulin. 

PMID- 24586197
TI  - Insertional mutagenesis and deep profiling reveals gene hierarchies and a Myc/p53
      dependent bottleneck in lymphomagenesis.
AB  - Retroviral insertional mutagenesis (RIM) is a powerful tool for cancer genomics
      that was combined in this study with deep sequencing (RIM/DS) to facilitate a
      comprehensive analysis of lymphoma progression. Transgenic mice expressing two
      potent collaborating oncogenes in the germ line (CD2-MYC, -Runx2) develop rapid
      onset tumours that can be accelerated and rendered polyclonal by neonatal Moloney
      murine leukaemia virus (MoMLV) infection. RIM/DS analysis of 28 polyclonal
      lymphomas identified 771 common insertion sites (CISs) defining a 'progression
      network' that encompassed a remarkably large fraction of known MoMLV target
      genes, with further strong indications of oncogenic selection above the
      background of MoMLV integration preference. Progression driven by RIM was
      characterised as a Darwinian process of clonal competition engaging proliferation
      control networks downstream of cytokine and T-cell receptor signalling. Enhancer
      mode activation accounted for the most efficiently selected CIS target genes,
      including Ccr7 as the most prominent of a set of chemokine receptors driving
      paracrine growth stimulation and lymphoma dissemination. Another large target
      gene subset including candidate tumour suppressors was disrupted by intragenic
      insertions. A second RIM/DS screen comparing lymphomas of wild-type and parental
      transgenics showed that CD2-MYC tumours are virtually dependent on activation of
      Runx family genes in strong preference to other potent Myc collaborating genes
      (Gfi1, Notch1). Ikzf1 was identified as a novel collaborating gene for Runx2 and
      illustrated the interface between integration preference and oncogenic selection.
      Lymphoma target genes for MoMLV can be classified into (a) a small set of master
      regulators that confer self-renewal; overcoming p53 and other failsafe pathways
      and (b) a large group of progression genes that control autonomous proliferation
      in transformed cells. These findings provide insights into retroviral biology,
      human cancer genetics and the safety of vector-mediated gene therapy. 

PMID- 24586198
TI  - High-resolution profiling of stationary-phase survival reveals yeast longevity
      factors and their genetic interactions.
AB  - Lifespan is influenced by a large number of conserved proteins and gene
      regulatory pathways. Here, we introduce a strategy for systematically finding
      such longevity factors in Saccharomyces cerevisiae and scoring the genetic
      interactions (epistasis) among these factors. Specifically, we developed an
      automated competition-based assay for chronological lifespan, defined as
      stationary-phase survival of yeast populations, and used it to phenotype over
      5,600 single- or double-gene knockouts at unprecedented quantitative resolution.
      We found that 14% of the viable yeast mutant strains were affected in their
      stationary-phase survival; the extent of true-positive chronological lifespan
      factors was estimated by accounting for the effects of culture aeration and
      adaptive regrowth. We show that lifespan extension by dietary restriction depends
      on the Swr1 histone-exchange complex and that a functional link between autophagy
      and the lipid-homeostasis factor Arv1 has an impact on cellular lifespan.
      Importantly, we describe the first genetic interaction network based on aging
      phenotypes, which successfully recapitulated the core-autophagy machinery and
      confirmed a role of the human tumor suppressor PTEN homologue in yeast lifespan
      and phosphatidylinositol phosphate metabolism. Our quantitative analysis of
      longevity factors and their genetic interactions provides insights into the gene
      network interactions of aging cells. 

PMID- 24586199
TI  - Arf4 is required for Mammalian development but dispensable for ciliary assembly.
AB  - The primary cilium is a sensory organelle, defects in which cause a wide range of
      human diseases including retinal degeneration, polycystic kidney disease and
      birth defects. The sensory functions of cilia require specific receptors to be
      targeted to the ciliary subdomain of the plasma membrane. Arf4 has been proposed
      to sort cargo destined for the cilium at the Golgi complex and deemed a key
      regulator of ciliary protein trafficking. In this work, we show that Arf4 binds
      to the ciliary targeting sequence (CTS) of fibrocystin. Knockdown of Arf4
      indicates that it is not absolutely required for trafficking of the fibrocystin
      CTS to cilia as steady-state CTS levels are unaffected. However, we did observe a
      delay in delivery of newly synthesized CTS from the Golgi complex to the cilium
      when Arf4 was reduced. Arf4 mutant mice are embryonic lethal and die at mid
      gestation shortly after node formation. Nodal cilia appeared normal and
      functioned properly to break left-right symmetry in Arf4 mutant embryos. At this
      stage of development Arf4 expression is highest in the visceral endoderm but we
      did not detect cilia on these cells. In the visceral endoderm, the lack of Arf4
      caused defects in cell structure and apical protein localization. This work
      suggests that while Arf4 is not required for ciliary assembly, it is important
      for the efficient transport of fibrocystin to cilia, and also plays critical
      roles in non-ciliary processes. 

PMID- 24586200
TI  - Negative feedback and transcriptional overshooting in a regulatory network for
      horizontal gene transfer.
AB  - Horizontal gene transfer (HGT) is a major force driving bacterial evolution.
      Because of their ability to cross inter-species barriers, bacterial plasmids are
      essential agents for HGT. This ability, however, poses specific requisites on
      plasmid physiology, in particular the need to overcome a multilevel selection
      process with opposing demands. We analyzed the transcriptional network of plasmid
      R388, one of the most promiscuous plasmids in Proteobacteria. Transcriptional
      analysis by fluorescence expression profiling and quantitative PCR revealed a
      regulatory network controlled by six transcriptional repressors. The regulatory
      network relied on strong promoters, which were tightly repressed in negative
      feedback loops. Computational simulations and theoretical analysis indicated that
      this architecture would show a transcriptional burst after plasmid conjugation,
      linking the magnitude of the feedback gain with the intensity of the
      transcriptional burst. Experimental analysis showed that transcriptional
      overshooting occurred when the plasmid invaded a new population of susceptible
      cells. We propose that transcriptional overshooting allows genome rebooting after
      horizontal gene transfer, and might have an adaptive role in overcoming the
      opposing demands of multilevel selection. 

PMID- 24586201
TI  - Molecular evidence for the inverse comorbidity between central nervous system
      disorders and cancers detected by transcriptomic meta-analyses.
AB  - There is epidemiological evidence that patients with certain Central Nervous
      System (CNS) disorders have a lower than expected probability of developing some
      types of Cancer. We tested here the hypothesis that this inverse comorbidity is
      driven by molecular processes common to CNS disorders and Cancers, and that are
      deregulated in opposite directions. We conducted transcriptomic meta-analyses of
      three CNS disorders (Alzheimer's disease, Parkinson's disease and Schizophrenia)
      and three Cancer types (Lung, Prostate, Colorectal) previously described with
      inverse comorbidities. A significant overlap was observed between the genes
      upregulated in CNS disorders and downregulated in Cancers, as well as between the
      genes downregulated in CNS disorders and upregulated in Cancers. We also observed
      expression deregulations in opposite directions at the level of pathways. Our
      analysis points to specific genes and pathways, the upregulation of which could
      increase the incidence of CNS disorders and simultaneously lower the risk of
      developing Cancer, while the downregulation of another set of genes and pathways
      could contribute to a decrease in the incidence of CNS disorders while increasing
      the Cancer risk. These results reinforce the previously proposed involvement of
      the PIN1 gene, Wnt and P53 pathways, and reveal potential new candidates, in
      particular related with protein degradation processes. 

PMID- 24586202
TI  - The Caenorhabditis elegans iodotyrosine deiodinase ortholog SUP-18 functions
      through a conserved channel SC-box to regulate the muscle two-pore domain
      potassium channel SUP-9.
AB  - Loss-of-function mutations in the Caenorhabditis elegans gene sup-18 suppress the
      defects in muscle contraction conferred by a gain-of-function mutation in SUP-10,
      a presumptive regulatory subunit of the SUP-9 two-pore domain K(+) channel
      associated with muscle membranes. We cloned sup-18 and found that it encodes the
      C. elegans ortholog of mammalian iodotyrosine deiodinase (IYD), an NADH
      oxidase/flavin reductase that functions in iodine recycling and is important for
      the biosynthesis of thyroid hormones that regulate metabolism. The FMN-binding
      site of mammalian IYD is conserved in SUP-18, which appears to require catalytic
      activity to function. Genetic analyses suggest that SUP-10 can function with SUP
      18 to activate SUP-9 through a pathway that is independent of the presumptive SUP
      9 regulatory subunit UNC-93. We identified a novel evolutionarily conserved
      serine-cysteine-rich region in the C-terminal cytoplasmic domain of SUP-9
      required for its specific activation by SUP-10 and SUP-18 but not by UNC-93.
      Since two-pore domain K(+) channels regulate the resting membrane potentials of
      numerous cell types, we suggest that the SUP-18 IYD regulates the activity of the
      SUP-9 channel using NADH as a coenzyme and thus couples the metabolic state of
      muscle cells to muscle membrane excitability. 

PMID- 24586204
TI  - Fifteen years later: hard and soft selection sweeps confirm a large population
      number for HIV in vivo.

PMID- 24586203
TI  - miR-100 induces epithelial-mesenchymal transition but suppresses tumorigenesis,
      migration and invasion.
AB  - Whether epithelial-mesenchymal transition (EMT) is always linked to increased
      tumorigenicity is controversial. Through microRNA (miRNA) expression profiling of
      mammary epithelial cells overexpressing Twist, Snail or ZEB1, we identified miR
      100 as a novel EMT inducer. Surprisingly, miR-100 inhibits the tumorigenicity,
      motility and invasiveness of mammary tumor cells, and is commonly downregulated
      in human breast cancer due to hypermethylation of its host gene MIR100HG. The EMT
      inducing and tumor-suppressing effects of miR-100 are mediated by distinct
      targets. While miR-100 downregulates E-cadherin by targeting SMARCA5, a regulator
      of CDH1 promoter methylation, this miRNA suppresses tumorigenesis, cell movement
      and invasion in vitro and in vivo through direct targeting of HOXA1, a gene that
      is both oncogenic and pro-invasive, leading to repression of multiple HOXA1
      downstream targets involved in oncogenesis and invasiveness. These findings
      provide a proof-of-principle that EMT and tumorigenicity are not always
      associated and that certain EMT inducers can inhibit tumorigenesis, migration and
      invasion. 

PMID- 24586205
TI  - Chromosome I controls chromosome II replication in Vibrio cholerae.
AB  - Control of chromosome replication involves a common set of regulators in
      eukaryotes, whereas bacteria with divided genomes use chromosome-specific
      regulators. How bacterial chromosomes might communicate for replication is not
      known. In Vibrio cholerae, which has two chromosomes (chrI and chrII),
      replication initiation is controlled by DnaA in chrI and by RctB in chrII. DnaA
      has binding sites at the chrI origin of replication as well as outside the
      origin. RctB likewise binds at the chrII origin and, as shown here, to external
      sites. The binding to the external sites in chrII inhibits chrII replication. A
      new kind of site was found in chrI that enhances chrII replication. Consistent
      with its enhancing activity, the chrI site increased RctB binding to those chrII
      origin sites that stimulate replication and decreased binding to other sites that
      inhibit replication. The differential effect on binding suggests that the new
      site remodels RctB. The chaperone-like activity of the site is supported by the
      finding that it could relieve the dependence of chrII replication on chaperone
      proteins DnaJ and DnaK. The presence of a site in chrI that specifically controls
      chrII replication suggests a mechanism for communication between the two
      chromosomes for replication. 

PMID- 24586207
TI  - Within-host spatiotemporal dynamics of plant virus infection at the cellular
      level.
AB  - A multicellular organism is not a monolayer of cells in a flask; it is a complex,
      spatially structured environment, offering both challenges and opportunities for
      viruses to thrive. Whereas virus infection dynamics at the host and within-cell
      levels have been documented, the intermediate between-cell level remains poorly
      understood. Here, we used flow cytometry to measure the infection status of
      thousands of individual cells in virus-infected plants. This approach allowed us
      to determine accurately the number of cells infected by two virus variants in the
      same host, over space and time as the virus colonizes the host. We found a low
      overall frequency of cellular infection (<0.3), and few cells were coinfected by
      both virus variants (<0.1). We then estimated the cellular contagion rate (R),
      the number of secondary infections per infected cell per day. R ranged from 2.43
      to values not significantly different from zero, and generally decreased over
      time. Estimates of the cellular multiplicity of infection (MOI), the number of
      virions infecting a cell, were low (<1.5). Variance of virus-genotype frequencies
      increased strongly from leaf to cell levels, in agreement with a low MOI.
      Finally, there were leaf-dependent differences in the ease with which a leaf
      could be colonized, and the number of virions effectively colonizing a leaf. The
      modeling of infection patterns suggests that the aggregation of virus-infected
      cells plays a key role in limiting spread; matching the observation that cell-to
      cell movement of plant viruses can result in patches of infection. Our results
      show that virus expansion at the between-cell level is restricted, probably due
      to the host environment and virus infection itself. 

PMID- 24586206
TI  - Influenza virus drug resistance: a time-sampled population genetics perspective.
AB  - The challenge of distinguishing genetic drift from selection remains a central
      focus of population genetics. Time-sampled data may provide a powerful tool for
      distinguishing these processes, and we here propose approximate Bayesian, maximum
      likelihood, and analytical methods for the inference of demography and selection
      from time course data. Utilizing these novel statistical and computational tools,
      we evaluate whole-genome datasets of an influenza A H1N1 strain in the presence
      and absence of oseltamivir (an inhibitor of neuraminidase) collected at thirteen
      time points. Results reveal a striking consistency amongst the three estimation
      procedures developed, showing strongly increased selection pressure in the
      presence of drug treatment. Importantly, these approaches re-identify the known
      oseltamivir resistance site, successfully validating the approaches used.
      Enticingly, a number of previously unknown variants have also been identified as
      being positively selected. Results are interpreted in the light of Fisher's
      Geometric Model, allowing for a quantification of the increased distance to
      optimum exerted by the presence of drug, and theoretical predictions regarding
      the distribution of beneficial fitness effects of contending mutations are
      empirically tested. Further, given the fit to expectations of the Geometric
      Model, results suggest the ability to predict certain aspects of viral evolution
      in response to changing host environments and novel selective pressures. 

PMID- 24586208
TI  - MicroRNAs located in the Hox gene clusters are implicated in huntington's disease
      pathogenesis.
AB  - Transcriptional dysregulation has long been recognized as central to the
      pathogenesis of Huntington's disease (HD). MicroRNAs (miRNAs) represent a major
      system of post-transcriptional regulation, by either preventing translational
      initiation or by targeting transcripts for storage or for degradation. Using next
      generation miRNA sequencing in prefrontal cortex (Brodmann Area 9) of twelve HD
      and nine controls, we identified five miRNAs (miR-10b-5p, miR-196a-5p, miR-196b
      5p, miR-615-3p and miR-1247-5p) up-regulated in HD at genome-wide significance
      (FDR q-value<0.05). Three of these, miR-196a-5p, miR-196b-5p and miR-615-3p, were
      expressed at near zero levels in control brains. Expression was verified for all
      five miRNAs using reverse transcription quantitative PCR and all but miR-1247-5p
      were replicated in an independent sample (8HD/8C). Ectopic miR-10b-5p expression
      in PC12 HTT-Q73 cells increased survival by MTT assay and cell viability staining
      suggesting increased expression may be a protective response. All of the miRNAs
      but miR-1247-5p are located in intergenic regions of Hox clusters. Total mRNA
      sequencing in the same samples identified fifteen of 55 genes within the Hox
      cluster gene regions as differentially expressed in HD, and the Hox genes
      immediately adjacent to the four Hox cluster miRNAs as up-regulated. Pathway
      analysis of mRNA targets of these miRNAs implicated functions for neuronal
      differentiation, neurite outgrowth, cell death and survival. In regression models
      among the HD brains, huntingtin CAG repeat size, onset age and age at death were
      independently found to be inversely related to miR-10b-5p levels. CAG repeat size
      and onset age were independently inversely related to miR-196a-5p, onset age was
      inversely related to miR-196b-5p and age at death was inversely related to miR
      615-3p expression. These results suggest these Hox-related miRNAs may be involved
      in neuroprotective response in HD. Recently, miRNAs have shown promise as
      biomarkers for human diseases and given their relationship to disease expression,
      these miRNAs are biomarker candidates in HD. 

PMID- 24586209
TI  - Selective disruption of aurora C kinase reveals distinct functions from aurora B
      kinase during meiosis in mouse oocytes.
AB  - Aurora B kinase (AURKB) is the catalytic subunit of the chromosomal passenger
      complex (CPC), an essential regulator of chromosome segregation. In mitosis, the
      CPC is required to regulate kinetochore microtubule (K-MT) attachments, the
      spindle assembly checkpoint, and cytokinesis. Germ cells express an AURKB
      homolog, AURKC, which can also function in the CPC. Separation of AURKB and AURKC
      function during meiosis in oocytes by conventional approaches has not been
      successful. Therefore, the meiotic function of AURKC is still not fully
      understood. Here, we describe an ATP-binding-pocket-AURKC mutant, that when
      expressed in mouse oocytes specifically perturbs AURKC-CPC and not AURKB-CPC
      function. Using this mutant we show for the first time that AURKC has functions
      that do not overlap with AURKB. These functions include regulating localized CPC
      activity and regulating chromosome alignment and K-MT attachments at metaphase of
      meiosis I (Met I). We find that AURKC-CPC is not the sole CPC complex that
      regulates the spindle assembly checkpoint in meiosis, and as a result most AURKC
      perturbed oocytes arrest at Met I. A small subset of oocytes do proceed through
      cytokinesis normally, suggesting that AURKC-CPC is not the sole CPC complex
      during telophase I. But, the resulting eggs are aneuploid, indicating that AURKC
      is a critical regulator of meiotic chromosome segregation in female gametes.
      Taken together, these data suggest that mammalian oocytes contain AURKC to
      efficiently execute meiosis I and ensure high-quality eggs necessary for sexual
      reproduction. 

PMID- 24586210
TI  - Convergence of Light and ABA signaling on the ABI5 promoter.
AB  - Light is one of the most important environmental cues regulating multiple aspects
      of plant growth and development, and abscisic acid (ABA) is a plant hormone that
      plays important roles during many phases of the plant life cycle and in plants'
      responses to various environmental stresses. How plants integrate the external
      light signal with endogenous ABA pathway for better adaptation and survival
      remains poorly understood. Here, we show that BBX21 (also known as SALT TOLERANCE
      HOMOLOG 2), a B-box (BBX) protein previously shown to positively regulate
      seedling photomorphogenesis, is also involved in ABA signaling. Our genetic data
      show that BBX21 may act upstream of several ABA INSENSITIVE (ABI) genes and
      ELONGATED HYPOCOTYL 5 (HY5) in ABA control of seed germination. Previous studies
      showed that HY5 acts as a direct activator of ABI5 expression, and that BBX21
      interacts with HY5. We further demonstrate that BBX21 negatively regulates ABI5
      expression by interfering with HY5 binding to the ABI5 promoter. In addition,
      ABI5 was shown to directly activate its own expression, whereas BBX21 negatively
      regulates this activity by directly interacting with ABI5. Together, our study
      indicates that BBX21 coordinates with HY5 and ABI5 on the ABI5 promoter and that
      these transcriptional regulators work in concert to integrate light and ABA
      signaling in Arabidopsis thaliana. 

PMID- 24586211
TI  - Plasma cholesterol-induced lesion networks activated before regression of early,
      mature, and advanced atherosclerosis.
AB  - Plasma cholesterol lowering (PCL) slows and sometimes prevents progression of
      atherosclerosis and may even lead to regression. Little is known about how
      molecular processes in the atherosclerotic arterial wall respond to PCL and
      modify responses to atherosclerosis regression. We studied atherosclerosis
      regression and global gene expression responses to PCL (>=80%) and to
      atherosclerosis regression itself in early, mature, and advanced lesions. In
      atherosclerotic aortic wall from Ldlr(-/-)Apob (100/100) Mttp (flox/flox)Mx1-Cre
      mice, atherosclerosis regressed after PCL regardless of lesion stage. However,
      near-complete regression was observed only in mice with early lesions; mice with
      mature and advanced lesions were left with regression-resistant, relatively
      unstable plaque remnants. Atherosclerosis genes responding to PCL before
      regression, unlike those responding to the regression itself, were enriched in
      inherited risk for coronary artery disease and myocardial infarction, indicating
      causality. Inference of transcription factor (TF) regulatory networks of these
      PCL-responsive gene sets revealed largely different networks in early, mature,
      and advanced lesions. In early lesions, PPARG was identified as a specific master
      regulator of the PCL-responsive atherosclerosis TF-regulatory network, whereas in
      mature and advanced lesions, the specific master regulators were MLL5 and
      SRSF10/XRN2, respectively. In a THP-1 foam cell model of atherosclerosis
      regression, siRNA targeting of these master regulators activated the time-point
      specific TF-regulatory networks and altered the accumulation of cholesterol
      esters. We conclude that PCL leads to complete atherosclerosis regression only in
      mice with early lesions. Identified master regulators and related PCL-responsive
      TF-regulatory networks will be interesting targets to enhance PCL-mediated
      regression of mature and advanced atherosclerotic lesions. 

PMID- 24586212
TI  - MicroRNA-133 inhibits behavioral aggregation by controlling dopamine synthesis in
      locusts.
AB  - Phenotypic plasticity is ubiquitous and primarily controlled by interactions
      between environmental and genetic factors. The migratory locust, a worldwide
      pest, exhibits pronounced phenotypic plasticity, which is a population density
      dependent transition that occurs between the gregarious and solitary phases.
      Genes involved in dopamine synthesis have been shown to regulate the phase
      transition of locusts. However, the function of microRNAs in this process remains
      unknown. In this study, we report the participation of miR-133 in dopamine
      production and the behavioral transition by negatively regulating two critical
      genes, henna and pale, in the dopamine pathway. miR-133 participated in the post
      transcriptional regulation of henna and pale by binding to their coding region
      and 3' untranslated region, respectively. miR-133 displayed cellular co
      localization with henna/pale in the protocerebrum, and its expression in the
      protocerebrum was negatively correlated with henna and pale expression. Moreover,
      miR-133 agomir delivery suppressed henna and pale expression, which consequently
      decreased dopamine production, thus resulting in the behavioral shift of the
      locusts from the gregarious phase to the solitary phase. Increasing the dopamine
      content could rescue the solitary phenotype, which was induced by miR-133 agomir
      delivery. Conversely, miR-133 inhibition increased the expression of henna and
      pale, resulting in the gregarious-like behavior of solitary locusts; this
      gregarious phenotype could be rescued by RNA interference of henna and pale. This
      study shows the novel function and modulation pattern of a miRNA in phenotypic
      plasticity and provides insight into the underlying molecular mechanisms of the
      phase transition of locusts. 

PMID- 24586216
TI  - Cardiovascular protection by beta-blockade in hypertensive haemodialysis
      patients: the Hypertension in Haemodialysis Patients Treated With Atenolol or
      Lisinopril (HDPAL) trial.

PMID- 24586213
TI  - Transcriptome-wide analyses of 5'-ends in RNase J mutants of a gram-positive
      pathogen reveal a role in RNA maturation, regulation and degradation.
AB  - RNA decay and maturation have in recent years been recognised as major regulatory
      mechanisms in bacteria. In contrast to Escherichia coli, the Firmicute (Gram
      positive) bacteria often do not encode the well-studied endonuclease RNase E, but
      instead rely on the endonucleases RNase Y, RNase J1 and RNase J2, of which the
      latter two have additionally been shown to have 5' to 3' exonucleolytic activity.
      We have previously demonstrated that these RNases could be deleted individually
      in the pathogenic Firmicute Staphylococcus aureus; however, we here present that,
      outside a narrow permissive window of growth conditions, deleting one or both of
      the RNase J genes presents serious difficulties for the cell. Moreover, an active
      site mutant of RNase J1 behaved like a deletion, whereas no phenotypes were
      detected for the RNase J2 active site mutant. Furthermore, in order to study the
      in vivo enzymatic activity of RNase J1 and J2, a method was developed to map the
      exact 5'-ends of mature and processed RNA, on a global scale. An enrichment of 5'
      RNA ends could be seen in the RNase J mutants, suggesting that their
      exonucleolytic activity is crucial for normal degradation of bulk RNA. Using the
      data to examine specific RNAs, we demonstrated that RNase J activity is needed
      for correct 5' maturation of both the 16S rRNA and the RNase P ribozyme, and can
      also inactivate the latter, possibly as quality control. Additional examples show
      that RNase J perform initial cleavages, apparently competing with ribosomes for
      access to mRNAs. The novel 5' mapping assay offers an exceptionally detailed view
      of RNase activity, and reveals that the roles of RNase J proteins are diverse,
      ranging from maturation and post-transcriptional regulation to degradation. 

PMID- 24586218
TI  - Pleiotropic effect of common variants at ABO Glycosyltranferase locus in 9q32 on
      plasma levels of pancreatic lipase and angiotensin converting enzyme.
AB  - For forty-three clinical test values presumably associated to common complex
      human diseases, we carried out a genome-wide association study using 600K SNPs in
      a general Japanese population of 1,639 individuals (1,252 after quality control
      procedures) drawn from a regional cohort, followed by a replication study for
      statistically significant SNPs (p = 1.95 * 10(-9)-8.34 * 10(-39)) using an
      independent population of 1,671 from another cohort. In this single two-stage
      study, we newly found strong and robust associations of common variants at the
      ABO histo-blood glycosyltransferase locus in 9q32 with the plasma levels of
      pancreatic lipase (P-LIP), in addition to successful confirmation of the known
      ABO association of angiotensin converting enzyme (ACE) independent of the ACE1
      gene in 17q23.2 with the ACE level. Our results are compatible with the
      previously reported association between the ABO gene and pancreatic cancer, and
      show that the effect of these common variants at the ABO locus on the P-LIP and
      ACE levels is largely opposing and pleiotropic.

PMID- 24586221
TI  - A variational approach to the analysis of dissipative electromechanical systems.
AB  - We develop a method for systematically constructing Lagrangian functions for
      dissipative mechanical, electrical, and electromechanical systems. We derive the
      equations of motion for some typical electromechanical systems using
      deterministic principles that are strictly variational. We do not use any ad hoc
      features that are added on after the analysis has been completed, such as the
      Rayleigh dissipation function. We generalise the concept of potential, and define
      generalised potentials for dissipative lumped system elements. Our innovation
      offers a unified approach to the analysis of electromechanical systems where
      there are energy and power terms in both the mechanical and electrical parts of
      the system. Using our novel technique, we can take advantage of the analytic
      approach from mechanics, and we can apply these powerful analytical methods to
      electrical and to electromechanical systems. We can analyse systems that include
      non-conservative forces. Our methodology is deterministic, and does does require
      any special intuition, and is thus suitable for automation via a computer-based
      algebra package. 

PMID- 24586219
TI  - Higher serum direct bilirubin levels were associated with a lower risk of
      incident chronic kidney disease in middle aged Korean men.
AB  - BACKGROUND: The association between serum bilirubin levels and incident chronic
      kidney disease (CKD) in the general population is unknown. We aimed to examine
      the association between serum bilirubin concentration (total, direct, and
      indirect) and the risk of incident CKD. METHODS AND FINDINGS: Longitudinal cohort
      study of 12,823 Korean male workers 30 to 59 years old without CKD or proteinuria
      at baseline participating in medical health checkup program in a large worksite.
      Study participants were followed for incident CKD from 2002 through 2011.
      Estimated glomerular filtration rate (eGFR) was estimated by using the CKD-EPI
      equation. CKD was defined as eGFR <60 mL/min per 1.73 m(2). Parametric Cox models
      and pooled logistic regression models were used to estimate adjusted hazard
      ratios for incident CKD. We observed 238 incident cases of CKD during 70,515.8
      person-years of follow-up. In age-adjusted models, the hazard ratios for CKD
      comparing quartiles 2-4 vs. quartile 1 of serum direct bilirubin were 0.93 (95%
      CI 0.67-1.28), 0.88 (0.60-1.27) and 0.60 (0.42-0.88), respectively. In
      multivariable models, the adjusted hazard ratio for CKD comparing the highest to
      the lowest quartile of serum direct bilirubin levels was 0.60 (95% CI 0.41-0.87;
      P trend = 0.01). Neither serum total nor indirect bilirubin levels were
      significantly associated with the incidence of CKD. CONCLUSIONS: Higher serum
      direct bilirubin levels were significantly associated with a lower risk of
      developing CKD, even adjusting for a variety of cardiometabolic parameters.
      Further research is needed to elucidate the mechanisms underlying this
      association and to establish the role of serum direct bilirubin as a marker for
      CKD risk.

PMID- 24586220
TI  - Parasite co-infections and their impact on survival of indigenous cattle.
AB  - In natural populations, individuals may be infected with multiple distinct
      pathogens at a time. These pathogens may act independently or interact with each
      other and the host through various mechanisms, with resultant varying outcomes on
      host health and survival. To study effects of pathogens and their interactions on
      host survival, we followed 548 zebu cattle during their first year of life,
      determining their infection and clinical status every 5 weeks. Using a
      combination of clinical signs observed before death, laboratory diagnostic test
      results, gross-lesions on post-mortem examination, histo-pathology results and
      survival analysis statistical techniques, cause-specific aetiology for each death
      case were determined, and effect of co-infections in observed mortality patterns.
      East Coast fever (ECF) caused by protozoan parasite Theileria parva and
      haemonchosis were the most important diseases associated with calf mortality,
      together accounting for over half (52%) of all deaths due to infectious diseases.
      Co-infection with Trypanosoma species increased the hazard for ECF death by 6
      times (1.4-25; 95% CI). In addition, the hazard for ECF death was increased in
      the presence of Strongyle eggs, and this was burden dependent. An increase by
      1000 Strongyle eggs per gram of faeces count was associated with a 1.5 times (1.4
      1.6; 95% CI) increase in the hazard for ECF mortality. Deaths due to haemonchosis
      were burden dependent, with a 70% increase in hazard for death for every increase
      in strongyle eggs per gram count of 1000. These findings have important
      implications for disease control strategies, suggesting a need to consider co
      infections in epidemiological studies as opposed to single-pathogen focus, and
      benefits of an integrated approach to helminths and East Coast fever disease
      control. 

PMID- 24586222
TI  - How to make a synthetic multicellular computer.
AB  - Biological systems perform computations at multiple scales and they do so in a
      robust way. Engineering metaphors have often been used in order to provide a
      rationale for modeling cellular and molecular computing networks and as the basis
      for their synthetic design. However, a major constraint in this mapping between
      electronic and wet computational circuits is the wiring problem. Although wires
      are identical within electronic devices, they must be different when using
      synthetic biology designs. Moreover, in most cases the designed molecular systems
      cannot be reused for other functions. A new approximation allows us to simplify
      the problem by using synthetic cellular consortia where the output of the
      computation is distributed over multiple engineered cells. By evolving circuits
      in silico, we can obtain the minimal sets of Boolean units required to solve the
      given problem at the lowest cost using cellular consortia. Our analysis reveals
      that the basic set of logic units is typically non-standard. Among the most
      common units, the so called inverted IMPLIES (N-Implies) appears to be one of the
      most important elements along with the NOT and AND functions. Although NOR and
      NAND gates are widely used in electronics, evolved circuits based on combinations
      of these gates are rare, thus suggesting that the strategy of combining the same
      basic logic gates might be inappropriate in order to easily implement synthetic
      computational constructs. The implications for future synthetic designs, the
      general view of synthetic biology as a standard engineering domain, as well as
      potencial drawbacks are outlined. 

PMID- 24586223
TI  - Regional alterations in purkinje cell density in patients with autism.
AB  - Neuropathological studies, using a variety of techniques, have reported a
      decrease in Purkinje cell (PC) density in the cerebellum in autism. We have used
      a systematic sampling technique that significantly reduces experimenter bias and
      variance to estimate PC densities in the postmortem brains of eight clinically
      well-documented individuals with autism, and eight age- and gender-matched
      controls. Four cerebellar regions were analyzed: a sensorimotor area comprised of
      hemispheric lobules IV-VI, crus I & II of the posterior lobe, and lobule X of the
      flocculonodular lobe. Overall PC density was thus estimated using data from all
      three cerebellar lobes and was found to be lower in the cases with autism as
      compared to controls, an effect that was most prominent in crus I and II
      (p<0.05). Lobule X demonstrated a trend towards lower PC density in only the
      males with autism (p = 0.05). Brain weight, a correlate of tissue volume, was
      found to significantly contribute to the lower lobule X PC density observed in
      males with autism, but not to the finding of lower PC density in crus I & II.
      Therefore, lower crus I & II PC density in autism is more likely due to a lower
      number of PCs. The PC density in lobule X was found to correlate with the ADI-R
      measure of the patient's use of social eye contact (R2 = -0.75, p = 0.012). These
      findings support the hypothesis that abnormal PC density may contribute to
      selected clinical features of the autism phenotype.

PMID- 24586224
TI  - Inferring regulatory networks by combining perturbation screens and steady state
      gene expression profiles.
AB  - Reconstructing transcriptional regulatory networks is an important task in
      functional genomics. Data obtained from experiments that perturb genes by
      knockouts or RNA interference contain useful information for addressing this
      reconstruction problem. However, such data can be limited in size and/or are
      expensive to acquire. On the other hand, observational data of the organism in
      steady state (e.g., wild-type) are more readily available, but their
      informational content is inadequate for the task at hand. We develop a
      computational approach to appropriately utilize both data sources for estimating
      a regulatory network. The proposed approach is based on a three-step algorithm to
      estimate the underlying directed but cyclic network, that uses as input both
      perturbation screens and steady state gene expression data. In the first step,
      the algorithm determines causal orderings of the genes that are consistent with
      the perturbation data, by combining an exhaustive search method with a fast
      heuristic that in turn couples a Monte Carlo technique with a fast search
      algorithm. In the second step, for each obtained causal ordering, a regulatory
      network is estimated using a penalized likelihood based method, while in the
      third step a consensus network is constructed from the highest scored ones.
      Extensive computational experiments show that the algorithm performs well in
      reconstructing the underlying network and clearly outperforms competing
      approaches that rely only on a single data source. Further, it is established
      that the algorithm produces a consistent estimate of the regulatory network. 

PMID- 24586225
TI  - Fat pad entrapment at the hip: a new diagnosis.
AB  - PURPOSE: To establish if a positive impingement sign in femoroacetabular
      impingement (FAI) may result from entrapment of the fat pad located at the
      anterior head-neck junction of the upper femur. This fat pad is routinely removed
      before any cam lesion excision. METHODS: We report a prospective study of 142
      consecutive hip arthroscopies for symptomatic FAI where the aim was to remove the
      arthroscopically identified area of impingement, not necessarily to create a
      spherical femoral head. Patients were divided into two groups. Group 1 (n = 92;
      34 females, 58 males), where a cam-type bony FAI lesion was identified and
      excised in addition to the fat pad which overlay it, and Group 2 (n = 50; 29
      females, 21 males) where the only identified point of impingement was a prominent
      fat pad. In this situation the fat pad was excised in isolation and the
      underlying bone preserved. Patients were assessed preoperatively, at six weeks,
      six months, one year and two years with a modified Harris hip score (mHHS).
      RESULTS: Both groups were comparable preoperatively for mean age, mean alpha
      angle and mean anterior offset ratio. Both groups improved significantly after
      surgery at all time points. However, Group 1 (fat pad and bone resection)
      demonstrated 16.0% improvement in mHHS by two years while for Group 2 (fat pad
      resection only) the improvement was 18.9% (p = 0.628). CONCLUSIONS: The fat pad
      found at the anterior head/neck junction of the hip joint can be a source of pain
      and we propose fat pad entrapment as a new, previously undescribed diagnosis. Our
      findings also suggest that a large number of cam lesions are being excised
      unnecessarily and that further efforts should be made to understand the role of
      the fat pad as a source of groin discomfort. LEVEL OF EVIDENCE: Level IV, case
      series.

PMID- 24586226
TI  - TG1042 (Adenovirus-interferon-gamma) in primary cutaneous B-cell lymphomas: a
      phase II clinical trial.
AB  - RATIONAL: While a variety of registered therapies exist for Cutaneous T Cell
      Lymphoma, no such therapy is available for Cutaneous B Cell Therapy. In this
      context we performed a phase II, open label, multicenter, non-comparative study
      to evaluate the efficacy and safety of repeated intra-lesional administrations of
      TG1042 (adenovirus-interferon-gamma) in patients with relapsing primary cutaneous
      B-cell lymphomas (CBCL). METHOD: Thirteen patients have been enrolled and
      received intralesional injections of TG1042 containing 5*10(10) viral particles
      into up to six lesions simultaneously. Injections were performed on days 1, 8 and
      15 of each of four consecutive 28 day cycles. RESULTS: Eleven (85%) out of 13
      enrolled patients showed an objective response after injections of TG1042. Seven
      patients (54%) exhibited complete and four (31%) displayed partial response. The
      median time to disease progression in the study population was 23.5 months (range
      6.25 to 26+). Most commonly observed adverse events were minor to moderate flu
      like symptoms, fatigue and injection site reactions. CONCLUSIONS: Our study
      showed that treatment with TG1042 was associated with a clinical benefit in the
      majority of the patients with relapsing CBCL, including tumor regression, a
      clinically meaningful duration of response and a good treatment tolerance. TRIAL
      REGISTRATION: www.clinicaltrials.govNCT00394693.

PMID- 24586227
TI  - HIV infection of hepatocytes results in a modest increase in hepatitis C virus
      expression in vitro.
AB  - Previous studies demonstrate that soluble HIV proteins impact both hepatocyte
      function and HCV replication in vitro. It has also been reported that HIV can
      productively infect hepatocytes. We therefore investigated the impact of HIV
      infection of hepatocytes on HCV expression. The Huh7.5JFH1 cell line that
      constitutively expresses infectious HCV was infected with the lab-adapted strains
      HIVNL4-3 or HIVYK-JRCSF. HCV expression was quantified via HCV core antigen
      ELISA, Western blot, and strand-specific real-time PCR for positive-sense and
      negative-sense HCV RNA. After HIVNL4-3 infection of Huh7.5JFH1 cells, positive
      sense and negative-sense HCV RNA levels were elevated compared to HIV uninfected
      cells. Increased HCV RNA synthesis was also observed after infection of
      Huh7.5JFH1 cells with HIVYK-JRCSF. HIV-induced HCV core production was decreased
      in the presence of the anti-HIV drugs AZT, T20, and raltegravir, although these
      medications had a minimal effect on HCV expression in the absence of HIV. HCV
      core, NS3, and NS5A protein expression were increased after HIV infection of
      Huh7.5JFH1 cells. Chemically inactivated HIV had a minimal effect on HCV
      expression in Huh7.5JFH1 cells suggesting that ongoing viral replication was
      critical. These data demonstrate that HIV induces HCV RNA synthesis and protein
      production in vitro and complement previous in vivo reports that HCV RNA levels
      are elevated in individuals with HIV/HCV co-infection compared to those with HCV
      mono-infection. These findings suggest that HIV suppression may be a critical
      factor in controlling liver disease, particularly if the underlying liver disease
      is not treated. 

PMID- 24586228
TI  - Physiological tolerance times while wearing explosive ordnance disposal
      protective clothing in simulated environmental extremes.
AB  - Explosive ordnance disposal (EOD) technicians are required to wear protective
      clothing to protect themselves from the threat of overpressure, fragmentation,
      impact and heat. The engineering requirements to minimise these threats results
      in an extremely heavy and cumbersome clothing ensemble that increases the
      internal heat generation of the wearer, while the clothing's thermal properties
      reduce heat dissipation. This study aimed to evaluate the heat strain encountered
      wearing EOD protective clothing in simulated environmental extremes across a
      range of differing work intensities. Eight healthy males [age 25 +/- 6 years
      (mean +/- sd), height 180 +/- 7 cm, body mass 79 +/- 9 kg, VO2max 57 +/- 6 ml(.)
      kg(-1.)min(-1)] undertook nine trials while wearing an EOD9 suit (weighing 33.4
      kg). The trials involved walking on a treadmill at 2.5, 4 and 5.5 km ? h(-1) at
      each of the following environmental conditions, 21, 30 and 37  degrees C wet bulb
      globe temperature (WBGT) in a randomised controlled crossover design. The trials
      were ceased if the participants' core temperature reached 39  degrees C, if heart
      rate exceeded 90% of maximum, if walking time reached 60 minutes or due to
      fatigue/nausea. Tolerance times ranged from 10-60 minutes and were significantly
      reduced in the higher walking speeds and environmental conditions. In a total of
      15 trials (21%) participants completed 60 minutes of walking; however, this was
      predominantly at the slower walking speeds in the 21  degrees C WBGT environment.
      Of the remaining 57 trials, 50 were ceased, due to attainment of 90% maximal
      heart rate. These near maximal heart rates resulted in moderate-high levels of
      physiological strain in all trials, despite core temperature only reaching 39 
      degrees C in one of the 72 trials.

PMID- 24586230
TI  - The effects of Mary Rose conservation treatment on iron oxidation processes and
      microbial communities contributing to acid production in marine archaeological
      timbers.
AB  - The Tudor warship the Mary Rose has reached an important transition point in her
      conservation. The 19 year long process of spraying with polyethylene glycol (PEG)
      has been completed (April 29(th) 2013) and the hull is air drying under tightly
      controlled conditions. Acidophilic bacteria capable of oxidising iron and sulfur
      have been previously identified and enriched from unpreserved timbers of the Mary
      Rose, demonstrating that biological pathways of iron and sulfur oxidization
      existed potentially in this wood, before preservation with PEG. This study was
      designed to establish if the recycled PEG spray system was a reservoir of
      microorganisms capable of iron and sulfur oxidization during preservation of the
      Mary Rose. Microbial enrichments derived from PEG impregnated biofilm collected
      from underneath the Mary Rose hull, were examined to better understand the
      processes of cycling of iron. X-ray absorption spectroscopy was utilised to
      demonstrate the biological contribution to production of sulfuric acid in the
      wood. Using molecular microbiological techniques to examine these enrichment
      cultures, PEG was found to mediate a shift in the microbial community from a co
      culture of Stenotrophomonas and Brevunidimonas sp, to a co-culture of
      Stenotrophomonas and the iron oxidising Alicyclobacillus sp. Evidence is
      presented that PEG is not an inert substance in relation to the redox cycling of
      iron. This is the first demonstration that solutions of PEG used in the
      conservation of the Mary Rose are promoting the oxidation of ferrous iron in
      acidic solutions, in which spontaneous abiotic oxidation does not occur in water.
      Critically, these results suggest PEG mediated redox cycling of iron between
      valence states in solutions of 75% PEG 200 and 50% PEG 2000 (v/v) at pH 3.0, with
      serious implications for the future use of PEG as a conservation material of iron
      rich wooden archaeological artefacts. 

PMID- 24586229
TI  - A 3-marker index improves the identification of iron disorders in CKD anaemia.
AB  - BACKGROUND: Iron disorders are common and complex in chronic kidney disease
      (CKD). We sought to determine whether a 3-marker index would improve the
      classification of iron disorders in CKD anaemia. METHODS: We studied the
      association between Hb level and iron indexes combining 2 or 3 of the following
      markers: serum ferritin (<40 ng/mL), transferrin saturation (TSAT<20%) and total
      iron binding capacity (TIBC<50 umol/L) in 1011 outpatients with non-dialysis CKD
      participating in the Nephrotest study. All had glomerular filtration rates
      measured (mGFR) by (51)Cr-EDTA renal clearance; 199 also had hepcidin measures.
      RESULTS: The TSAT-TIBC-ferritin index explained Hb variation better than indexes
      combining TSAT-TIBC or ferritin-TSAT. It showed hypotransferrinaemia and non
      inflammatory functional iron deficiency (ID) to be more common than either
      absolute or inflammatory ID: 20%, 19%, 6%, and 2%, respectively. Hb was lower in
      all abnormal, compared with normal, iron profiles, and decreased more when mGFR
      was below 30 mL/min/1.73 m(2) (interaction p<0.0001). In patients with mGFR<30
      mL/min/1.73 m(2), the Hb decreases associated with hypotransferrinaemia, non
      inflammatory functional ID, and absolute ID were 0.83+/-0.16 g/dL, 0.51+/-0.18
      and 0.89+/-0.29, respectively. Compared with normal iron profiles, hepcidin was
      severely depressed in absolute ID but higher in hypotransferrinaemia.
      CONCLUSIONS: The combined TSAT-TIBC-ferritin index identifies
      hypotransferrinaemia and non-inflammatory functional ID as the major mechanisms
      of iron disorders in CKD anaemia. Both disorders were associated with a greater
      decrease in Hb when mGFR was <30 mL/min/1.73 m(2). Taking these iron profiles
      into account may be useful in stratifying patients in clinical trials of CKD
      anaemia and might improve the management of iron therapy.

PMID- 24586232
TI  - Communicating hydrocephalus following eosinophilic meningitis is pathogenic for
      chronic Viliuisk encephalomyelitis in Northeastern Siberia.
AB  - BACKGROUND: Viliuisk encephalomyelitis (VE) is an endemic neurological disease in
      Northeast Siberia and generally considered to be a chronic encephalomyelitis of
      unknown origin actually spreading in the Sakha (Yakutian) Republic. METHODOLOGY
      AND PRINCIPLE FINDINGS: In search for the pathophysiology and causative agent of
      VE, we performed a cross-sectional study on clinical, serological and
      neuroimaging data on chronic VE patients during two medical expeditions to three
      villages within the Viliuiski river basin in the Republic of Sakha in 2000 and to
      the capital Yakutsk in 2006. The severity of the core clinical picture with
      predominant sensory ataxia, gait apraxia, lower limb spasticity, cognitive
      impairment and bladder dysfunction correlated with the degree of MRI findings
      showing enlargement of inner ventricular spaces as in communicating
      hydrocephalus. Laboratory studies revealed transient eosinophilia during the
      preceding acute meningitis-like phase, but no ongoing inflammatory process in the
      CSF. We found immune reactions against Toxocara canis in the majority of chronic
      VE patients but rarely in controls (P = 0.025; Fisher's exact test). Histological
      analysis of subacute to subchronic VE brain samples showed eosinophilic
      infiltrations with no signs of persistent Toxocara canis infection. CONCLUSIONS
      AND SIGNIFICANCE: Our data showed that pressure by the communicating
      hydrocephalus as a mechanical factor is the major pathogenic mechanism in chronic
      VE, most likely triggered by eosinophilic meningitis. There are no signs for an
      ongoing inflammatory process in chronic VE. The past eosinophilic reaction in VE
      might be caused by Toxocara ssp. infection and might therefore represent the
      first hint for an initial cause leading to the development of chronic VE. Our
      data provide a framework for future studies and potential therapeutic
      interventions for this enigmatic epidemic neurological disease potentially
      spreading in Sakha Republic.

PMID- 24586231
TI  - Immune escape mutants of Highly Pathogenic Avian Influenza H5N1 selected using
      polyclonal sera: identification of key amino acids in the HA protein.
AB  - Evolution of Avian Influenza (AI) viruses--especially of the Highly Pathogenic
      Avian Influenza (HPAI) H5N1 subtype--is a major issue for the poultry industry.
      HPAI H5N1 epidemics are associated with huge economic losses and are sometimes
      connected to human morbidity and mortality. Vaccination (either as a preventive
      measure or as a means to control outbreaks) is an approach that splits the
      scientific community, due to the risk of it being a potential driving force in
      HPAI evolution through the selection of mutants able to escape vaccination
      induced immunity. It is therefore essential to study how mutations are selected
      due to immune pressure. To this effect, we performed an in vitro selection of
      mutants from HPAI A/turkey/Turkey/1/05 (H5N1), using immune pressure from
      homologous polyclonal sera. After 42 rounds of selection, we identified 5 amino
      acid substitutions in the Haemagglutinin (HA) protein, most of which were located
      in areas of antigenic importance and suspected to be prone to selection pressure.
      We report that most of the mutations took place early in the selection process.
      Finally, our antigenic cartography studies showed that the antigenic distance
      between the selected isolates and their parent strain increased with passage
      number.

PMID- 24586233
TI  - Intra- and interspecific differences in diet quality and composition in a large
      herbivore community.
AB  - Species diversity in large herbivore communities is often explained by niche
      segregation allowed by differences in body mass and digestive morphophysiological
      features. Based on large number of gut samples in fall and winter, we analysed
      the temporal dynamics of diet composition, quality and interspecific overlap of 4
      coexisting mountain herbivores. We tested whether the relative consumption of
      grass and browse differed among species of different rumen types (moose-type and
      intermediate-type), whether diet was of lower quality for the largest species,
      whether we could identify plant species which determined diet quality, and
      whether these plants, which could be "key-food-resources" were similar for all
      herbivores. Our analyses revealed that (1) body mass and rumen types were overall
      poor predictors of diet composition and quality, although the roe deer, a species
      with a moose-type rumen was confirmed as an "obligatory non grazer", while red
      deer, the largest species, had the most lignified diet; (2) diet overlap among
      herbivores was well predicted by rumen type (high among species of intermediate
      types only), when measured over broad plant groups, (3) the relationship between
      diet composition and quality differed among herbivore species, and the actual
      plant species used during winter which determined the diet quality, was herbivore
      species-specific. Even if diets overlapped to a great extent, the species
      specific relationships between diet composition and quality suggest that
      herbivores may select different plant species within similar plant group types,
      or different plant parts and that this, along with other behavioural mechanisms
      of ecological niche segregation, may contribute to the coexistence of large
      herbivores of relatively similar body mass, as observed in mountain ecosystems. 

PMID- 24586234
TI  - International trade of CITES listed bird species in China.
AB  - Commercial trade of wild birds may devastate wild bird populations. Convention on
      International Trade in Endangered Species of Wild Fauna and Flora (CITES)
      controls the trade of wild species listed in its appendices to avoid these
      species being threatened by international trade. China used to be one of the
      major trading countries with significant bird trade with foreign countries; on
      the other hand, China is a country with unique avian fauna, many Important Bird
      Areas and critically endangered bird species. What is the role of the country in
      world wild bird trade? What kind of insights can we extract from trade records
      for improving future management of wild bird trade in the country? We retrieved
      and analyzed international trade records of the CITES listed bird species of
      China from 1981 to 2010 from the CITES Trade Database maintained by United
      Nations Environment Program and World Conservation Monitoring Centre (UNEP-WCMC).
      We found that: (1) International trade of live birds in China peaked during the
      late 1990s, then decreased to the level before the surge of trade in a few years,
      the trade dynamics of wild birds may be affected by governmental policy and the
      outbreak of avian influenza during the period. (2) Most frequently traded CITES
      Appendix listed birds in China were parrots, most of which were exotic species to
      the country. (3) Birds were mainly traded for commercial purpose. Exotic birds in
      trade were mainly captive-bred while the most Chinese birds traded
      internationally were captured from the wild. Since many bird species in
      international trade are threatened to extinction, China should take stricter
      measures on importing of wild-captured birds and should collaborate with the
      countries of original in the international bird trade to avoid unsustainable
      harvesting of wild birds. It is urgent for China to carry out population surveys
      on those domestic bird species once in significant international trade and to
      make better conservation decisions based on population status of those birds. In
      addition, more scientific researchers should be encouraged to participate in the
      wildlife trade management to avoid misreporting trade data or biased analyses of
      the trade records. 

PMID- 24586235
TI  - Single stock dynamics on high-frequency data: from a compressed coding
      perspective.
AB  - High-frequency return, trading volume and transaction number are digitally coded
      via a nonparametric computing algorithm, called hierarchical factor segmentation
      (HFS), and then are coupled together to reveal a single stock dynamics without
      global state-space structural assumptions. The base-8 digital coding sequence,
      which is capable of revealing contrasting aggregation against sparsity of extreme
      events, is further compressed into a shortened sequence of state transitions.
      This compressed digital code sequence vividly demonstrates that the aggregation
      of large absolute returns is the primary driving force for stimulating both the
      aggregations of large trading volumes and transaction numbers. The state of
      system-wise synchrony is manifested with very frequent recurrence in the stock
      dynamics. And this data-driven dynamic mechanism is seen to correspondingly vary
      as the global market transiting in and out of contraction-expansion cycles. These
      results not only elaborate the stock dynamics of interest to a fuller extent, but
      also contradict some classical theories in finance. Overall this version of stock
      dynamics is potentially more coherent and realistic, especially when the current
      financial market is increasingly powered by high-frequency trading via computer
      algorithms, rather than by individual investors. 

PMID- 24586236
TI  - Mapping the kinetic barriers of a Large RNA molecule's folding landscape.
AB  - The folding of linear polymers into discrete three-dimensional structures is
      often required for biological function. The formation of long-lived intermediates
      is a hallmark of the folding of large RNA molecules due to the ruggedness of
      their energy landscapes. The precise thermodynamic nature of the barriers
      (whether enthalpic or entropic) that leads to intermediate formation is still
      poorly characterized in large structured RNA molecules. A classic approach to
      analyzing kinetic barriers are temperature dependent studies analyzed with
      Eyring's transition state theory. We applied Eyring's theory to time-resolved
      hydroxyl radical (*OH) footprinting kinetics progress curves collected at eight
      temperature from 21.5  degrees C to 51  degrees C to characterize the
      thermodynamic nature of folding intermediate formation for the Mg(2+)-mediated
      folding of the Tetrahymena thermophila group I ribozyme. A common kinetic model
      configuration describes this RNA folding reaction over the entire temperature
      range studied consisting of primary (fast) transitions to misfolded intermediates
      followed by much slower secondary transitions, consistent with previous studies.
      Eyring analysis reveals that the primary transitions are moderate in magnitude
      and primarily enthalpic in nature. In contrast, the secondary transitions are
      daunting in magnitude and entropic in nature. The entropic character of the
      secondary transitions is consistent with structural rearrangement of the
      intermediate species to the final folded form. This segregation of kinetic
      control reveals distinctly different molecular mechanisms during the two stages
      of RNA folding and documents the importance of entropic barriers to defining
      rugged RNA folding landscapes.

PMID- 24586237
TI  - Clinical analysis of cause, treatment and prognosis in acute kidney injury
      patients.
AB  - Acute kidney injury (AKI) is characterized by an abrupt decline in renal
      function, resulting in an inability to secrete waste products and maintain
      electrolyte and water balance, and is associated with high risks of morbidity and
      mortality. This study retrospectively analyzed clinical data, treatment, and
      prognosis of 271 hospitalized patients (172 males and 99 females) diagnosed with
      AKI from December, 2008 to December, 2011. In addition, this study explored the
      association between the cause of AKI and prognosis, severity and treatment of
      AKI. The severity of AKI was classified according to the Acute Kidney Injury
      Network (AKIN) criteria. Renal recovery was defined as a decrease in a serum
      creatinine level to the normal value. Prerenal, renal, and postrenal causes
      accounted for 36.5% (99 patients), 46.5% (126 patients) and 17.0% (46 patients),
      respectively, of the incidence of AKI. Conservative, surgical, and renal
      replacement treatments were given to 180 (66.4%), 30 (11.1%) and 61 patients
      (22.5%), respectively. The overall recovery rate was 21.0%, and the mortality
      rate was 19.6%. Levels of Cl(-), Na(+) and carbon dioxide combining power
      decreased with increasing severity of AKI. Cause and treatment were significantly
      associated with AKI prognosis. Likewise, the severity of AKI was significantly
      associated with cause, treatment and prognosis. Multivariate logistic regression
      analysis found that respiratory injury and multiple organ dysfunction syndrome
      (MODS) were associated with AKI patient death. Cause, treatment and AKIN stage
      are associated with the prognosis of AKI. Respiratory injury and MODS are
      prognostic factors for death of AKI patients. 

PMID- 24586238
TI  - Prostaglandin E2 reduces the release and infectivity of new cell-free virions and
      cell-to-cell HIV-1 transfer.
AB  - BACKGROUND: The course of human immunodeficiency virus type-1 (HIV-1) infection
      is influenced by a complex interplay between viral and host factors. HIV
      infection stimulates several proinflammatory genes, such as cyclooxigense-2 (COX
      2), which leads to an increase in prostaglandin (PG) levels in the plasma of HIV
      1-infected patients. These genes play an indeterminate role in HIV replication
      and pathogenesis. The effect of prostaglandin E2 (PGE2) on HIV infection is quite
      controversial and even contradictory, so we sought to determine the role of PGE2
      and the signal transduction pathways involved in HIV infection to elucidate
      possible new targets for antiretrovirals. RESULTS: Our results suggest that PGE2
      post-infection treatment acts in the late stages of the viral cycle to reduce HIV
      replication. Interestingly, viral protein synthesis was not affected, but a loss
      of progeny virus production was observed. No modulation of CD4 CXCR4 and CCR5
      receptor expression, cell proliferation, or activation after PGE2 treatment was
      detected. Moreover, PGE2 induced an increase in intracellular cAMP (cyclic AMP)
      levels through the EP2/EP4 receptors. PGE2 effects were mimicked by dbcAMP and by
      a specific Epac (exchange protein directly activated by cyclic AMP) agonist, 8
      Cpt-cAMP. Treatment with PGE2 increased Rap1 activity, decreased RhoA activity
      and subsequently reduced the polymerization of actin by approximately 30%
      compared with untreated cells. In connection with this finding, polarized viral
      assembly platforms enriched in Gag were disrupted, altering HIV cell-to-cell
      transfer and the infectivity of new virions. CONCLUSIONS: Our results demonstrate
      that PGE2, through Epac and Rap activation, alters the transport of newly
      synthesized HIV-1 components to the assembly site, reducing the release and
      infectivity of new cell-free virions and cell-to-cell HIV-1 transfer.

PMID- 24586239
TI  - Physical activity assessment in patients with axial spondyloarthritis compared to
      healthy controls: a technology-based approach.
AB  - INTRODUCTION: Traditionally, assessment in axial Spondyloarthritis (aSpA)
      includes the evaluation of the capacity to execute tasks, conceptualized as
      physical function. The role of physical activity, defined as movement-related
      energy expenditure, is largely unknown and almost exclusively studied using
      patient-reported outcome measures. The aims of this observational cross-sectional
      study are to compare physical activity between patients with aSpA and healthy
      controls (HC) and to evaluate the contribution of disease activity to physical
      activity differences between groups. METHODS: Forty patients with aSpA were
      matched by age, gender, period of data acquisition in terms of days and season to
      40 HC. Physical activity was measured during five consecutive days (three
      weekdays and two weekend days) using ambulatory monitoring (SenseWear Armband).
      Self-reported disease activity was measured by the Bath Ankylosing Spondylitis
      Disease Activity Index (BASDAI). Differences in physical activity between
      patients with aSpA and HC were examined with Wilcoxon signed-rank tests and a
      mixed linear model. Difference scores between patients and HC were correlated
      with disease activity. RESULTS: Average weekly physical activity level (Med(IQR);
      HC:1.54(1.41-1.73); aSpA:1.45(1.31-1.67),MET) and energy expenditure
      (HC:36.40(33.43-41.01); aSpA:34.55(31.08-39.41),MET.hrs/day) were significantly
      lower in patients with aSpA. Analyses across intensity levels revealed no
      significant differences between groups for inactivity and time spent at light or
      moderate physical activities. In contrast, weekly averages of vigorous
      (HC:4.02(1.20-12.60); aSpA:0.00(0.00-1.20),min/d), very vigorous physical
      activities (HC0.00(0.00-1.08); aSpA:0.00(0.00-0.00),mind/d) and
      moderate/(very)vigorous combined (HC2.41(1.62-3.48); aSpA:1.63(1.20-2.82),hrs/d)
      were significantly lower in patients with aSpA. Disease activity did not interact
      with differences in physical activity between patients with aSpA and HC,
      evidenced by non-significant and very low correlations (range: -0.06-0.17)
      between BASDAI and HC-aSpA patients' difference scores. CONCLUSIONS: Patients
      with aSpA exhibit lower physical activity compared to HC and these differences
      are independent of self-reported disease activity. Further research on PA in
      patients with aSpA should be prioritized.

PMID- 24586240
TI  - Energy parameters and novel algorithms for an extended nearest neighbor energy
      model of RNA.
AB  - We describe the first algorithm and software, RNAenn, to compute the partition
      function and minimum free energy secondary structure for RNA with respect to an
      extended nearest neighbor energy model. Our next-nearest-neighbor triplet energy
      model appears to lead to somewhat more cooperative folding than does the nearest
      neighbor energy model, as judged by melting curves computed with RNAenn and with
      two popular software implementations for the nearest-neighbor energy model. A web
      server is available at http://bioinformatics.bc.edu/clotelab/RNAenn/. 

PMID- 24586241
TI  - Accurate and robust prediction of genetic relationship from whole-genome
      sequences.
AB  - Computing the genetic relationship between two humans is important to studies in
      genetics, genomics, genealogy, and forensics. Relationship algorithms may be
      sensitive to noise, such as that arising from sequencing errors or imperfect
      reference genomes. We developed an algorithm for estimation of genetic
      relationship by averaged blocks (GRAB) that is designed for whole-genome
      sequencing (WGS) data. GRAB segments the genome into blocks, calculates the
      fraction of blocks sharing identity, and then uses a classification tree to infer
      1st- to 5th- degree relationships and unrelated individuals. We evaluated GRAB on
      simulated and real sequenced families, and compared it with other software. GRAB
      achieves similar performance, and does not require knowledge of population
      background or phasing. GRAB can be used in workflows for identifying unreported
      relationships, validating reported relationships in family-based studies, and
      detection of sample-tracking errors or duplicate inclusion. The software is
      available at familygenomics.systemsbiology.net/grab. 

PMID- 24586242
TI  - A systematic review on the accuracy of diagnostic procedures for infravesical
      obstruction in boys.
AB  - BACKGROUND: Infravesical obstruction leads to kidney and bladder dysfunction in a
      significant proportion of boys. The aim of this review is to determine the value
      of diagnostic tests for ascertainment of infravesical obstruction in boys.
      METHODOLOGY: We searched PubMed and EMBASE databases until January 1, 2013, to
      identify papers that described original diagnostic accuracy research for
      infravesical obstruction in boys. We extracted information on (1) patient
      characteristics and clinical presentation of PUV and (2) diagnostic pathway, (3)
      diagnostic accuracy measures and (4) assessed risk of bias. PRINCIPAL FINDINGS:
      We retrieved 15 studies describing various diagnostic pathways in 1,189 boys
      suspected for infravesical obstruction. The included studies reflect a broad
      clinical spectrum of patients, but all failed to present a standardised approach
      to confirm the presence and severity of obstruction. The risk of bias of included
      studies is rather high due to work-up bias and missing data. CONCLUSIONS: As a
      consequence of low quality of methods of the available studies we put little
      confidence in the reported estimates for the diagnostic accuracy of US, VCUG and
      new additional tests for ruling in or ruling out infravesical obstruction. To
      date, firm evidence to support common diagnostic pathways is lacking. Hence, we
      are unable to draw conclusions on diagnostic accuracy of tests for infravesical
      obstruction. In order to be able to standardise the diagnostic pathway for
      infravesical obstruction, adequate design and transparent reporting is mandatory.

PMID- 24586243
TI  - Genetic polymorphisms in IGF-I and IGFBP-3 are associated with prostate cancer in
      the Chinese population.
AB  - Insulin-like growth factor-I (IGF-I) and IGF binding protein-3 (IGFBP-3) are
      members of the insulin-like growth factor (IGF) family that play important roles
      in carcinogenesis. We hypothesized that the functional polymorphisms in IGF-I and
      IGFBP-3 may be associated with the risk of prostate cancer (PCa) in the Chinese
      population. This hospital-based case-control study included 664 PCa patients and
      702 cancer-free controls. Nine SNPs in IGF-I and IGFBP-3 were genotyped using the
      TaqMan assay. The genetic associations between the pathogenesis and progression
      of PCa were assessed by logistic regression. We found that the genotype and
      allele frequency distribution of rs6218, rs35767 and rs5742612 were significantly
      different when comparing PCa cases to controls (P  = 0.005, 0.005 and 0.020,
      respectively). In the combined analysis, individuals with 2-6 risk alleles had an
      elevated risk of PCa compared to those with 0-1 risk alleles. We also found that
      the association between the combined risk alleles and the risk of PCa appeared
      stronger in the following subgroups: individuals older than 71 years of age (OR 
      = 1.41, 95%CI  = 1.05-1.91, P  = 0.020), nonsmokers (OR  = 1.68, 95%CI  = 1.21
      2.32, P  = 0.002), nondrinkers (OR  = 1.32, 95%CI  = 1.02-1.61, P  = 0.002), and
      those with a negative family history of PCa (OR  = 1.28, 95%CI  = 1.02-1.71, P  =
      0.022). Our results indicate that the three SNPs (rs6218, rs35767 and rs5742612)
      and the joint genotypes with 2-6 risk alleles, may contribute to the
      susceptibility to PCa, but not the progression, in the Chinese population.

PMID- 24586244
TI  - Quantitative determination of regional lesion volume and distribution in children
      and adults with relapsing-remitting multiple sclerosis.
AB  - INTRODUCTION: Onset of MS occurs during childhood in about 5% of cases. It is
      unclear whether very young age at MS onset, when the nervous system is still
      myelinating, affects MS lesion accrual or regional distribution. OBJECTIVE: To
      compare the frequency, volume and distribution of T2 and T1 lesions in children
      and adults with relapsing-remitting multiple sclerosis (RRMS). METHODS: Lesions
      were segmented on T2- and T1-weighted MRI images from 29 children and 29 adults
      with RRMS, matched for disease duration. RESULTS: All subjects exhibited T2
      weighted brain lesions. Children had higher whole-brain T2-weighted-lesion-volume
      (T2LV) compared to adults (mean (SD) in cm(3): 12.76(2.7) vs. 10.03(3.4),
      p<0.0013). The supratentorial-T2LV was similar in children and adults (8.45(1.7)
      vs. 7.94(1.7), mean (SD), p = 0.2582), but adults were more likely to have
      supratentorial lesions (96.5% vs. 68.9%, p<0.012). Children were more likely to
      have infratentorial-T2-weighted lesions (75.9% vs. 43.4%, p<0.03), specifically
      in the brainstem (62.1% vs. 26.7%, p<0.019) and the pons (48.3% vs. 17.24%,
      p<0.024), had higher infratentorial-T2-weighted-lesion counts (4.1(5.6) vs.
      1.45(2.3), p<0.021), a greater infratentorial-T2LV (4.31(2.7) vs. 2.08(2.4),
      p<0.0013), and a greater infratentorial-T1-weighted-lesion-volume (T1LV)
      (3.7(2.5) vs. 1.08(1.9), p<0.0007). Whole-brain-T1LV was higher in children
      (9.3(2.5) vs. 6.43(2.1), p>0.001). Adult MS patients had higher supratentorial
      T1LV (5.5(0.92) vs. 6.41(2.1), mean (SD), p<0.034), whereas children were more
      likely to have infratentorial-T1-weighted lesions (58.6% vs. 23.3%, p<0.015).
      DISCUSSION: Onset of MS during childhood is associated with a higher volume of
      brain lesions in the first few years of disease relative to adults. Children with
      MS are more likely than adults to have T2 and T1 lesions in the infratentorial
      white matter, raising the possibility of preferential immune targeting of more
      mature myelin. Children with MS have a lower supratentorial T1 lesion burden,
      possibly reflecting more effective remyelination and repair in brain regions that
      are still engaged in active primary myelination.

PMID- 24586245
TI  - Fear of birth defects is a major barrier to soil-transmitted helminth treatment
      (STH) for pregnant women in the Philippines.
AB  - The World Health Organization recommends anthelminthic treatment for pregnant
      women after the first trimester in soil-transmitted helminth (STH) endemic
      regions to prevent adverse maternal-fetal consequences. Although studies have
      shown the high prevalence of infection in the Philippines, no research has
      evaluated deworming practices. We hypothesized that pregnant women are not
      receiving deworming treatment and we aimed to identify barriers to World Health
      Organization guideline implementation. We conducted key informant interviews with
      local Department of Health (DOH) administrators, focus group discussions with
      nurses, midwives, and health care workers, and knowledge, attitudes, and
      practices surveys with women of reproductive age to elicit perspectives about
      deworming during pregnancy. Key informant interviews revealed that healthcare
      workers were not deworming pregnant women due to inadequate drug supply,
      infrastructure and personnel as well as fear of teratogenicity. Focus group
      discussions showed that healthcare workers similarly had not implemented
      guidelines due to infrastructure challenges and concerns for fetal malformations.
      The majority of local women believed that STH treatment causes side effects
      (74.8%) as well as maternal harm (67.3%) and fetal harm (77.9%). Women who were
      willing to take anthelminthics while pregnant had significantly greater knowledge
      as demonstrated by higher Treatment Scores (mean rank 146.92 versus 103.1, z = 
      4.40, p<0.001) and higher Birth Defect Scores (mean rank 128.09 versus 108.65, z
      = -2.43, p = 0.015). This study concludes that World Health Organization
      guidelines are not being implemented in the Philippines. Infrastructure, specific
      protocols, and education for providers and patients regarding anthelminthic
      treatment are necessary for the successful prevention of STH morbidity and
      mortality among pregnant women. 

PMID- 24586246
TI  - Surface chemical compositions and dispersity of starch nanocrystals formed by
      sulfuric and hydrochloric acid hydrolysis.
AB  - Surface chemical compositions of starch nanocrystals (SNC) prepared using
      sulfuric acid (H2SO4) and hydrochloric acid (HCl) hydrolysis were analyzed by X
      ray photoelectron spectroscopy (XPS) and FT-IR. The results showed that carboxyl
      groups and sulfate esters were presented in SNC after hydrolysis with H2SO4,
      while no sulfate esters were detected in SNC during HCl-hydrolysis. TEM results
      showed that, compared to H2SO4-hydrolyzed sample, a wider size distribution of
      SNC prepared by HCl-hydrolysis were observed. Zeta-potentials were -23.1 and 
      5.02 mV for H2SO4- and HCl-hydrolyzed SNC suspensions at pH 6.5, respectively.
      Nevertheless, the zeta-potential values decreased to -32.3 and -10.2 mV as the
      dispersion pH was adjusted to 10.6. After placed 48 h at pH 10.6, zeta-potential
      increased to -24.1 mV for H2SO4-hydrolyzed SNC, while no change was detected for
      HCl-hydrolyzed one. The higher zeta-potential and relative small particle
      distribution of SNC caused more stable suspensions compared to HCl-hydrolyzed
      sample. 

PMID- 24586247
TI  - Loss of myoferlin redirects breast cancer cell motility towards collective
      migration.
AB  - Cell migration plays a central role in the invasion and metastasis of tumors. As
      cells leave the primary tumor, they undergo an epithelial to mesenchymal
      transition (EMT) and migrate as single cells. Epithelial tumor cells may also
      migrate in a highly directional manner as a collective group in some settings. We
      previously discovered that myoferlin (MYOF) is overexpressed in breast cancer
      cells and depletion of MYOF results in a mesenchymal to epithelial transition
      (MET) and reduced invasion through extracellular matrix (ECM). However, the
      biomechanical mechanisms governing cell motility during MYOF depletion are poorly
      understood. We first demonstrated that lentivirus-driven shRNA-induced MYOF loss
      in MDA-MB-231 breast cancer cells (MDA-231(MYOF-KD)) leads to an epithelial
      morphology compared to the mesenchymal morphology observed in control (MDA
      231(LTVC)) and wild-type cells. Knockdown of MYOF led to significant reductions
      in cell migration velocity and MDA-231(MYOF-KD) cells migrated directionally and
      collectively, while MDA-231(LTVC) cells exhibited single cell migration.
      Decreased migration velocity and collective migration were accompanied by
      significant changes in cell mechanics. MDA-231(MYOF-KD) cells exhibited a 2-fold
      decrease in cell stiffness, a 2-fold increase in cell-substrate adhesion and a
      1.5-fold decrease in traction force generation. In vivo studies demonstrated that
      when immunocompromised mice were implanted with MDA-231(MYOF-KD) cells, tumors
      were smaller and demonstrated lower tumor burden. Moreover, MDA-231(MYOF-KD)
      tumors were highly circularized and did not invade locally into the adventia in
      contrast to MDA-231(LTVC)-injected animals. Thus MYOF loss is associated with a
      change in tumor formation in xenografts and leads to smaller, less invasive
      tumors. These data indicate that MYOF, a previously unrecognized protein in
      cancer, is involved in MDA-MB-231 cell migration and contributes to biomechanical
      alterations. Our results indicate that changes in biomechanical properties
      following loss of this protein may be an effective way to alter the invasive
      capacity of cancer cells.

PMID- 24586248
TI  - Analysis of resin-dentin interface morphology and bond strength evaluation of
      core materials for one stage post-endodontic restorations.
AB  - PURPOSE: Restoration of endodontically treated teeth using fiber posts in a one
      stage procedure gains more popularity and aims to create a secondary monoblock.
      Data of detailed analyses of so called "post-and-core-systems" with respect to
      morphological characteristics of the resin-dentin interface in combination with
      bond strength measurements of fiber posts luted with these materials are scarce.
      The present study aimed to analyze four different post-and-core-systems with two
      different adhesive approaches (self-etch and etch-and-rinse). MATERIALS AND
      METHODS: Human anterior teeth (n = 80) were endodontically treated and post space
      preparations and post placement were performed using the following systems:
      Rebilda Post/Rebilda DC/Futurabond DC (Voco) (RB), Luxapost/Luxacore Z/Luxabond
      Prebond and Luxabond A+B (DMG) (LC), X Post/Core X Flow/XP Bond and Self Cure
      Activator (Dentsply DeTrey) (CX), FRC Postec/MultiCore Flow/AdheSE DC (Ivoclar
      Vivadent) (MC). Adhesive systems and core materials of 10 specimens per group
      were labeled using fluorescent dyes and resin-dentin interfaces were analyzed
      using Confocal Laser Scanning Microscopy (CLSM). Bond strengths were evaluated
      using a push-out test. Data were analyzed using repeated measurement ANOVA and
      following post-hoc test. RESULTS: CLSM analyses revealed significant differences
      between groups with respect to the factors hybrid layer thickness (p<0.0005) and
      number of resin tags (p = 0.02; ANOVA). Bond strength was significantly affected
      by core material (p = 0.001), location inside the root canal (p<0.0005) and
      incorporation of fluorescent dyes (p = 0.036; ANOVA). CX [7.7 (4.4) MPa]
      demonstrated significantly lower bond strength compared to LC [14.2 (8.7) MPa]
      and RB [13.3 (3.7) MPa] (p<0.05; Tukey HSD) but did not differ significantly from
      MC [11.5 (3.5) MPa]. CONCLUSION: It can be concluded that bond strengths inside
      the root canal were not affected by the adhesive approach of the post-and-core
      system. All systems demonstrated homogenous hybrid layer formation and
      penetration into the dentinal tubules in spite of the complicating conditions for
      adhesion inside the root canal.

PMID- 24586249
TI  - Honokiol enhances paclitaxel efficacy in multi-drug resistant human cancer model
      through the induction of apoptosis.
AB  - Resistance to chemotherapy remains a major obstacle in cancer therapy. This study
      aimed to evaluate the molecular mechanism and efficacy of honokiol in inducing
      apoptosis and enhancing paclitaxel chemotherapy in pre-clinical multi-drug
      resistant (MDR) cancer models, including lineage-derived human MDR (KB-8-5, KB
      C1, KB-V1) and their parental drug sensitive KB-3-1 cancer cell lines. In vitro
      analyses demonstrated that honokiol effectively inhibited proliferation in KB-3-1
      cells and the MDR derivatives (IC50 ranging 3.35 +/- 0.13 ug/ml to 2.77 +/- 0.22
      ug/ml), despite their significant differences in response to paclitaxel (IC50
      ranging 1.66 +/- 0.09 ng/ml to 6560.9 +/- 439.52 ng/ml). Honokiol induced
      mitochondria-dependent and death receptor-mediated apoptosis in MDR KB cells,
      which was associated with inhibition of EGFR-STAT3 signaling and downregulation
      of STAT3 target genes. Combined treatment with honokiol and paclitaxel
      synergistically augmented cytotoxicity in MDR KB cells, compared with treatment
      with either agent alone in vitro. Importantly, the combined treatment
      significantly inhibited in vivo growth of KB-8-5 tumors in a subcutaneous model.
      Tumor tissues from the combination group displayed a significant inhibition of Ki
      67 expression and an increase in TUNEL-positive cells compared with the control
      group. These results suggest that targeting multidrug resistance using honokiol
      in combination with chemotherapy drugs may provide novel therapeutic
      opportunities.

PMID- 24586250
TI  - Genome and transcriptome analysis of the basidiomycetous yeast Pseudozyma
      antarctica producing extracellular glycolipids, mannosylerythritol lipids.
AB  - Pseudozyma antarctica is a non-pathogenic phyllosphere yeast known as an
      excellent producer of mannosylerythritol lipids (MELs), multi-functional
      extracellular glycolipids, from vegetable oils. To clarify the genetic
      characteristics of P. antarctica, we analyzed the 18 Mb genome of P. antarctica T
      34. On the basis of KOG analysis, the number of genes (219 genes) categorized
      into lipid transport and metabolism classification in P. antarctica was one and a
      half times larger than that of yeast Saccharomyces cerevisiae (140 genes). The
      gene encoding an ATP/citrate lyase (ACL) related to acetyl-CoA synthesis
      conserved in oleaginous strains was found in P. antarctica genome: the single ACL
      gene possesses the four domains identical to that of the human gene, whereas the
      other oleaginous ascomycetous species have the two genes covering the four
      domains. P. antarctica genome exhibited a remarkable degree of synteny to U.
      maydis genome, however, the comparison of the gene expression profiles under the
      culture on the two carbon sources, glucose and soybean oil, by the DNA microarray
      method revealed that transcriptomes between the two species were significantly
      different. In P. antarctica, expression of the gene sets relating fatty acid
      metabolism were markedly up-regulated under the oily conditions compared with
      glucose. Additionally, MEL biosynthesis cluster of P. antarctica was highly
      expressed regardless of the carbon source as compared to U. maydis. These results
      strongly indicate that P. antarctica has an oleaginous nature which is relevant
      to its non-pathogenic and MEL-overproducing characteristics. The analysis and
      dataset contribute to stimulate the development of improved strains with
      customized properties for high yield production of functional bio-based
      materials. 

PMID- 24586251
TI  - Are temperate canopy spiders tree-species specific?
AB  - Arboreal spiders in deciduous and coniferous trees were investigated on their
      distribution and diversity. Insecticidal knock-down was used to comprehensively
      sample spiders from 175 trees from 2001 to 2003 in the Bialowieza forest and
      three remote forests in Poland. We identified 140 species from 9273 adult
      spiders. Spider communities were distinguished between deciduous and coniferous
      trees. The richest fauna was collected from Quercus where beta diversity was also
      highest. A tree-species-specific pattern was clearly observed for Alnus,
      Carpinus, Picea and Pinus trees and also for those tree species that were fogged
      in only four or three replicates, namely Betula and Populus. This hitherto
      unrecognised association was mainly due to the community composition of common
      species identified in a Dufrene-Legendre indicator species analysis. It was not
      caused by spatial or temporal autocorrelation. Explaining tree-species
      specificity for generalist predators like spiders is difficult and has to involve
      physical and ecological tree parameters like linkage with the abundance of prey
      species. However, neither did we find a consistent correlation of prey group
      abundances with spiders nor could differences in spider guild composition explain
      the observed pattern. Our results hint towards the importance of deterministic
      mechanisms structuring communities of generalist canopy spiders although the
      casual relationship is not yet understood. 

PMID- 24586252
TI  - Transbronchial lung cryobiopsy in the diagnosis of fibrotic interstitial lung
      diseases.
AB  - BACKGROUND: Histology is a key element for the multidisciplinary diagnosis of
      fibrotic diffuse parenchymal lung diseases (f-DPLD) when the clinical
      radiological picture is nondiagnostic. Transbronchial lung cryobiopsy (TBLC) have
      been shown to be useful for obtaining large and well-preserved biopsies of lung
      parenchyma, but experience with TBLC in f-DPLD is limited. OBJECTIVES: To
      evaluate safety, feasibility and diagnostic yield of TBLC in f-DPLD. METHOD:
      Prospective study of 69 cases of TBLC using flexible cryoprobe in the clinical
      radiological setting of f-DPLD with nondiagnostic high resolution computed
      tomography (HRCT) features. RESULTS:  SAFETY: pneumothorax occurred in 19
      patients (28%). One patient (1.4%) died of acute exacerbation. Feasibility:
      adequate cryobiopsies were obtained in 68 cases (99%). The median size of
      cryobiopsies was 43.11 mm(2) (range, 11.94-76.25). Diagnostic yield: among
      adequate TBLC the pathologists were confident ("high confidence") that
      histopathologic criteria sufficient to define a specific pattern in 52 patients
      (76%), including 36 of 47 with UIP (77%) and 9 nonspecific interstitial pneumonia
      (6 fibrosing and 3 cellular), 2 desquamative interstitial pneumonia/respiratory
      bronchiolitis-interstitial lung disease, 1 organizing pneumonia, 1 eosinophilic
      pneumonia, 1 diffuse alveolar damage, 1 hypersensitivity pneumonitis and 1
      follicular bronchiolitis. In 11 diagnoses of UIP the pathologists were less
      confident ("low confidence"). Agreement between pathologists in the detection of
      UIP was very good with a Kappa coefficient of 0.83 (95% CI, 0.69-0.97). Using the
      current consensus guidelines for clinical-radiologic-pathologic correlation 32%
      (20/63) of cases were classified as Idiopathic Pulmonary Fibrosis (IPF), 30%
      (19/63) as possible IPF, 25% (16/63) as other f-DPLDs and 13% (8/63) were
      unclassifiable. CONCLUSIONS: TBLC in the diagnosis of f-DPLD appears safe and
      feasible. TBLC has a good diagnostic yield in the clinical-radiological setting
      of f-DPLD without diagnostic HRCT features of usual interstitial pneumonia.
      Future studies should consider TBLC as a potential alternative to SLBx in f-DPLD.

PMID- 24586254
TI  - Evidence for sex-segregated ocean distributions of first-winter wandering
      albatrosses at Crozet islands.
AB  - The highly mobile wandering albatrosses (Diomedea exulans) are adapted to
      navigate the extreme environment of the Southern Ocean and return to isolated
      islands to breed. Each year they cover several hundreds of thousands of
      kilometers during travels across the sea. Little is known about the dispersal
      flights and migration of young albatrosses. We tracked, by satellite telemetry,
      the departure dispersal of 13 juvenile wandering albatrosses from the Crozet
      Islands and compared them with tracks of 7 unrelated adults during the
      interbreeding season. We used the satellite tracks to identify different
      behavioural steps of the inherited migration program used by juvenile wandering
      albatrosses during their first solo-migration. Our results show that the juvenile
      wandering albatrosses from Crozet Islands moved to sex-specific foraging zones of
      the ocean using at departures selectively the wind. The results suggest that the
      inherited migration program used by the juvenile wandering albatrosses encode
      several distinct steps, based on inherited preferred departure routes,
      differences in migration distance between sexes, and selective use of winds.
      During long transportation flights the albatrosses were influenced by winds and
      both adult and juveniles followed approximate loxodrome (rhumbline) routes
      coinciding with the foraging zone and the specific latitudes of their destination
      areas. During the long segments of transportation flights across open seas the
      juveniles selected routes at more northerly latitudes than adults. 

PMID- 24586253
TI  - The role of IKKbeta in Venezuelan equine encephalitis virus infection.
AB  - Venezuelan equine encephalitis virus (VEEV) belongs to the genus Alphavirus,
      family Togaviridae. VEEV infection is characterized by extensive inflammation and
      studies from other laboratories implicated an involvement of the NF-kappaB
      cascade in the in vivo pathology. Initial studies indicated that at early time
      points of VEEV infection, the NF-kappaB complex was activated in cells infected
      with the TC-83 strain of VEEV. One upstream kinase that contributes to the
      phosphorylation of p65 is the IKKbeta component of the IKK complex. Our previous
      studies with Rift valley fever virus, which exhibited early activation of the NF
      kappaB cascade in infected cells, had indicated that the IKKbeta component
      underwent macromolecular reorganization to form a novel low molecular weight form
      unique to infected cells. This prompted us to investigate if the IKK complex
      undergoes a comparable macromolecular reorganization in VEEV infection. Size
      fractionated VEEV infected cell extracts indicated a macromolecular
      reorganization of IKKbeta in VEEV infected cells that resulted in formation of
      lower molecular weight complexes. Well-documented inhibitors of IKKbeta function,
      BAY-11-7082, BAY-11-7085 and IKK2 compound IV, were employed to determine whether
      IKKbeta function was required for the production of infectious progeny virus. A
      decrease in infectious viral particles and viral RNA copies was observed with
      inhibitor treatment in the attenuated and virulent strains of VEEV infection. In
      order to further validate the requirement of IKKbeta for VEEV replication, we
      over-expressed IKKbeta in cells and observed an increase in viral titers. In
      contrast, studies carried out using IKKbeta(-/-) cells demonstrated a decrease in
      VEEV replication. In vivo studies demonstrated that inhibitor treatment of TC-83
      infected mice increased their survival. Finally, proteomics studies have revealed
      that IKKbeta may interact with the viral protein nsP3. In conclusion, our studies
      have revealed that the host IKKbeta protein may be critically involved in VEEV
      replication. 

PMID- 24586255
TI  - New approach to increasing rice lodging resistance and biomass yield through the
      use of high gibberellin producing varieties.
AB  - Traditional breeding for high-yielding rice has been dependent on the widespread
      use of fertilizers and the cultivation of gibberellin (GA)-deficient semi-dwarf
      varieties. The use of semi-dwarf plants facilitates high grain yield since these
      varieties possess high levels of lodging resistance, and thus could support the
      high grain weight. Although this approach has been successful in increasing grain
      yield, it is desirable to further improve grain production and also to breed for
      high biomass. In this study, we re-examined the effect of GA on rice lodging
      resistance and biomass yield using several GA-deficient mutants (e.g. having
      defects in the biosynthesis or perception of GA), and high-GA producing line or
      mutant. GA-deficient mutants displayed improved bending-type lodging resistance
      due to their short stature; however they showed reduced breaking-type lodging
      resistance and reduced total biomass. In plants producing high amounts of GA, the
      bending-type lodging resistance was inferior to the original cultivars. The
      breaking-type lodging resistance was improved due to increased lignin
      accumulation and/or larger culm diameters. Further, these lines had an increase
      in total biomass weight. These results show that the use of rice cultivars
      producing high levels of GA would be a novel approach to create higher lodging
      resistance and biomass. 

PMID- 24586257
TI  - Game theory and extremal optimization for community detection in complex dynamic
      networks.
AB  - The detection of evolving communities in dynamic complex networks is a
      challenging problem that recently received attention from the research community.
      Dynamics clearly add another complexity dimension to the difficult task of
      community detection. Methods should be able to detect changes in the network
      structure and produce a set of community structures corresponding to different
      timestamps and reflecting the evolution in time of network data. We propose a
      novel approach based on game theory elements and extremal optimization to address
      dynamic communities detection. Thus, the problem is formulated as a mathematical
      game in which nodes take the role of players that seek to choose a community that
      maximizes their profit viewed as a fitness function. Numerical results obtained
      for both synthetic and real-world networks illustrate the competitive performance
      of this game theoretical approach. 

PMID- 24586256
TI  - The effect of a diiodothyronine mimetic on insulin sensitivity in male
      cardiometabolic patients: a double-blind randomized controlled trial.
AB  - BACKGROUND AND AIMS: Obesity and its associated cardiometabolic co-morbidities
      are increasing worldwide. Since thyroid hormone mimetics are capable of
      uncoupling the beneficial metabolic effects of thyroid hormones from their
      deleterious effects on heart, bone and muscle, this class of drug is considered
      as adjacent therapeutics to weight-lowering strategies. This study investigated
      the safety and efficacy of TRC150094, a thyroid hormone mimetic. MATERIALS AND
      METHODS: This 4-week, randomized, placebo-controlled, double-blind trial was
      conducted in India and The Netherlands. Forty subjects were randomized at a 1:1
      ratio to receive either TRC150094 dosed at 50 mg or placebo once daily for 4
      weeks. Hyperinsulinemic euglycemic clamp and (1)H-Magnetic Resonance Spectroscopy
      (MRS) were performed before and after treatment. RESULTS: At baseline, subjects
      were characterized by markedly impaired hepatic and peripheral insulin
      sensitivity. TRC150094 dosed 50 mg once daily was safe and well tolerated.
      Hepatic nor peripheral insulin sensitivity improved after TRC150094 treatment,
      expressed as the suppression of Endogenous Glucose Production from 59.5 to 62.1%;
      p = 0.477, and the rate of glucose disappearance from 28.8 to 26.4 umol kg(
      1)min(-1), p = 0.185. TRC150094 administration did not result in differences in
      fasting plasma free fatty acids from 0.51 to 0.51 mmol/L, p = 0.887 or in insulin
      mediated suppression of lipolysis from 57 to 54%, p = 0.102. Also, intrahepatic
      triglyceride content was unaltered. CONCLUSION: Collectively, these data show
      that, in contrast to the potent metabolic effects in experimental models,
      TRC150094 at a dose of 50 mg daily does not improve the metabolic homeostasis in
      subjects at an increased cardiometabolic risk. Further studies are needed to
      evaluate whether TRC150094 has beneficial effects in patients with more severe
      metabolic derangement, such as overt diabetes mellitus and hypertriglyceridemia.
      TRIAL REGISTRATION: clinicaltrials.gov NCT01408667.

PMID- 24586258
TI  - Staurosporine and extracellular matrix proteins mediate the conversion of small
      cell lung carcinoma cells into a neuron-like phenotype.
AB  - Small cell lung carcinomas (SCLCs) represent highly aggressive tumors with an
      overall five-year survival rate in the range of 5 to 10%. Here, we show that four
      out of five SCLC cell lines reversibly develop a neuron-like phenotype on
      extracellular matrix constituents such as fibronectin, laminin or thrombospondin
      upon staurosporine treatment in an RGD/integrin-mediated manner. Neurite-like
      processes extend rapidly with an average speed of 10 um per hour. Depending on
      the cell line, staurosporine treatment affects either cell cycle arrest in G2/M
      phase or induction of polyploidy. Neuron-like conversion, although not
      accompanied by alterations in the expression pattern of a panel of neuroendocrine
      genes, leads to changes in protein expression as determined by two-dimensional
      gel electrophoresis. It is likely that SCLC cells already harbour the complete
      molecular repertoire to convert into a neuron-like phenotype. More extensive
      studies are needed to evaluate whether the conversion potential of SCLC cells is
      suitable for therapeutic interventions. 

PMID- 24586259
TI  - Postoperative concomitant chemoradiotherapy improved treatment outcomes of
      patients with oral cavity cancer with multiple-node metastases but no other major
      risk factors.
AB  - PURPOSE: To investigate the results of postoperative radiotherapy (PORT) for the
      treatment of pathologic N2b/c squamous cell carcinoma of the oral cavity (OSCC).
      MATERIALS AND METHODS: This study reviewed cancer registry data collected in our
      hospital from 1998 to 2009 with the following inclusion criteria: primary OSCC,
      treatment with radical surgery, and multiple nodal metastases. Patients who had
      extracapsular spreading of the lymph node metastases or positive resection
      margins or who refused to undergo PORT were excluded. The prescribed dose of PORT
      was 60-66 Gy. Concurrent chemotherapy was optional. Patient characteristics,
      treatment parameters and clinical outcome were recorded. The primary end point
      was overall survival, and the secondary endpoint was disease status. RESULTS:
      There were 138 eligible cases, and the median follow-up period was 35 months. The
      3-year overall survival rate was 56%. Univariate analysis revealed that
      pathologic T4 status (pT4), bone marrow invasion, and lymphatic invasion were
      significantly correlated with poor outcome (p<0.05). Multivariate analysis showed
      that pT4, lymphatic invasion, and the no concurrent chemotherapy were independent
      poor prognostic factors (p<0.05). Fifty-four patients had tumor recurrence. The 3
      year recurrence-free survival rate was 59%. Skin invasion, pT4, and bone marrow
      invasion were correlated with poor prognosis in the univariate analysis (p<0.05).
      Only pT4 (p<0.01) and no concurrent chemotherapy (p = 0.03) were independently
      correlated with poor recurrence-free survival. CONCLUSION: For OSCC patients with
      multiple-node metastases without extracapsular spreading or positive resection
      margins, PORT without concurrent chemotherapy correlated to inferior outcome.
      Multiple lymph node metastases might be considered an indication for concurrent
      chemotherapy.

PMID- 24586260
TI  - Microbial succession during thermophilic digestion: the potential of
      Methanosarcina sp.
AB  - A distinct succession from a hydrolytic to a hydrogeno- and acetotrophic
      community was well documented by DGGE (denaturing gradient gel electrophoresis)
      and dHPLC (denaturing high performance liquid chromatography), and confirmed by
      qPCR (quantitative PCR) measurements and DNA sequence analyses. We could prove
      that Methanosarcina thermophila has been the most important key player during the
      investigated anaerobic digestion process. This organism was able to terminate a
      stagnation phase, most probable caused by a decreased pH and accumulated acetic
      acid following an initial hydrolytic stage. The lack in Methanosarcina sp. could
      not be compensated by high numbers of Methanothermobacter sp. or Methanoculleus
      sp., which were predominant during the initial or during the stagnation phase of
      the fermentation, respectively. 

PMID- 24586261
TI  - Interruption and non-adherence to long-term adjuvant hormone therapy is
      associated with adverse survival outcome of breast cancer women--an Asian
      population-based study.
AB  - This study aimed to evaluate the survival rate of women with breast cancer (BC)
      comparing persistence versus interruption and adherence versus non-adherence to
      adjuvant hormonal therapy (HT) in Asian population. Newly-diagnosed BC women from
      2003 to 2010 were retrospectively identified from the Taiwan National Health
      Insurance Research Database. HT prescriptions were extracted to define treatment
      interruption and medication possession ratio. Their impacts on mortality were
      estimated by Cox regression with time dependent covariates. Interruption (HR:
      1.32; 95% CI: 1.20, 1.46; P<0.0001) and non-adherence (HR: 1.45; 95% CI: 1.32,
      1.59; P<0.0001) to adjuvant HT were significantly associated with increased
      mortality. Interruption to tamoxifen in younger patients and in patients
      receiving surgery (OP) with adjuvant chemotherapy (CT) was associated with
      increasing mortality rate when compared with their counterparts. Non-adherence to
      AIs in both younger and senior age groups and in OP with CT group also resulted
      in increasing risk. Treatment interruption and non-adherence to adjuvant HT were
      found to be associated with the increasing all-cause mortality of the Asian BC
      women; a greater impact of interruption and non-adherence on mortality was
      especially found in the younger BC population. 

PMID- 24586262
TI  - A classical genetic solution to enhance the biosynthesis of anticancer
      phytochemicals in Andrographis paniculata Nees.
AB  - Andrographolides, the diterpene lactones, are major bioactive phytochemicals
      which could be found in different parts of the medicinal herb Andrographis
      paniculata. A number of such compounds namely andrographolide (AG),
      neoandrographolide (NAG), and 14-deoxy-11,12-didehydroandrographolide (DDAG) have
      already attracted a great deal of attention due to their potential therapeutic
      effects in hard-to-treat diseases such as cancers and HIV. Recently, they have
      also been considered as substrates for the discovery of novel pharmaceutical
      compounds. Nevertheless, there is still a huge gap in knowledge on the genetic
      pattern of the biosynthesis of these bioactive compounds. Hence, the present
      study aimed to investigate the genetic mechanisms controlling the biosynthesis of
      these phytochemicals using a diallel analysis. The high performance liquid
      chromatography analysis of the three andrographolides in 210 F1 progenies
      confirmed that the biosynthesis of these andrographolides was considerably
      increased via intraspecific hybridization. The results revealed high, moderate
      and low heterosis for DDAG, AG and NAG, respectively. Furthermore, the
      preponderance of non-additive gene actions was affirmed in the enhancement of the
      three andrographolides contents. The consequence of this type of gene action was
      the occurrence of high broad-sense and low narrow-sense heritabilities for the
      above mentioned andrographolides. The prevalence of non-additive gene action
      suggests the suitability of heterosis breeding and hybrid seed production as a
      preferred option to produce new plant varieties with higher andrographolide
      contents using the wild accessions of A. paniculata. Moreover, from an
      evolutionary point of view, the occurrence of population bottlenecks in the
      Malaysian accessions of A. paniculata was unveiled by observing a low level of
      additive genetic variance (VA ) for all the andrographolides. 

PMID- 24586263
TI  - Computational study on the inhibitor binding mode and allosteric regulation
      mechanism in hepatitis C virus NS3/4A protein.
AB  - HCV NS3/4A protein is an attractive therapeutic target responsible for harboring
      serine protease and RNA helicase activities during the viral replication. Small
      molecules binding at the interface between the protease and helicase domains can
      stabilize the closed conformation of the protein and thus block the catalytic
      function of HCV NS3/4A protein via an allosteric regulation mechanism. But the
      detailed mechanism remains elusive. Here, we aimed to provide some insight into
      the inhibitor binding mode and allosteric regulation mechanism of HCV NS3/4A
      protein by using computational methods. Four simulation systems were
      investigated. They include: apo state of HCV NS3/4A protein, HCV NS3/4A protein
      in complex with an allosteric inhibitor and the truncated form of the above two
      systems. The molecular dynamics simulation results indicate HCV NS3/4A protein in
      complex with the allosteric inhibitor 4VA adopts a closed conformation (inactive
      state), while the truncated apo protein adopts an open conformation (active
      state). Further residue interaction network analysis suggests the communication
      of the domain-domain interface play an important role in the transition from
      closed to open conformation of HCV NS3/4A protein. However, the inhibitor
      stabilizes the closed conformation through interaction with several key residues
      from both the protease and helicase domains, including His57, Asp79, Asp81,
      Asp168, Met485, Cys525 and Asp527, which blocks the information communication
      between the functional domains interface. Finally, a dynamic model about the
      allosteric regulation and conformational changes of HCV NS3/4A protein was
      proposed and could provide fundamental insights into the allosteric mechanism of
      HCV NS3/4A protein function regulation and design of new potent inhibitors. 

PMID- 24586265
TI  - Fate of clinical research studies after ethical approval--follow-up of study
      protocols until publication.
AB  - BACKGROUND: Many clinical studies are ultimately not fully published in peer
      reviewed journals. Underreporting of clinical research is wasteful and can result
      in biased estimates of treatment effect or harm, leading to recommendations that
      are inappropriate or even dangerous. METHODS: We assembled a cohort of clinical
      studies approved 2000-2002 by the Research Ethics Committee of the University of
      Freiburg, Germany. Published full articles were searched in electronic databases
      and investigators contacted. Data on study characteristics were extracted from
      protocols and corresponding publications. We characterized the cohort, quantified
      its publication outcome and compared protocols and publications for selected
      aspects. RESULTS: Of 917 approved studies, 807 were started and 110 were not,
      either locally or as a whole. Of the started studies, 576 (71%) were completed
      according to protocol, 128 (16%) discontinued and 42 (5%) are still ongoing; for
      61 (8%) there was no information about their course. We identified 782 full
      publications corresponding to 419 of the 807 initiated studies; the publication
      proportion was 52% (95% CI: 0.48-0.55). Study design was not significantly
      associated with subsequent publication. Multicentre status, international
      collaboration, large sample size and commercial or non-commercial funding were
      positively associated with subsequent publication. Commercial funding was
      mentioned in 203 (48%) protocols and in 205 (49%) of the publications. In most
      published studies (339; 81%) this information corresponded between protocol and
      publication. Most studies were published in English (367; 88%); some in German
      (25; 6%) or both languages (27; 6%). The local investigators were listed as (co
      )authors in the publications corresponding to 259 (62%) studies. CONCLUSION: Half
      of the clinical research conducted at a large German university medical centre
      remains unpublished; future research is built on an incomplete database. Research
      resources are likely wasted as neither health care professionals nor patients nor
      policy makers can use the results when making decisions.

PMID- 24586266
TI  - Structural diversity and initial oligomerization of PrP106-126 studied by replica
      exchange and conventional molecular dynamics simulations.
AB  - Prion diseases are marked by cerebral accumulation of the abnormal isoform of the
      prion protein. A fragment of prion protein composed of residues 106-126 (PrP106
      126) exhibits similar properties to full length prion and plays a key role in the
      conformational conversion from cellular prion to its pathogenic pattern. Soluble
      oligomers of PrP106-126 have been proposed to be responsible for neurotoxicity.
      However, the monomeric conformational space and initial oligomerization of PrP106
      126 are still obscure, which are very important for understanding the
      conformational conversion of PrP106-126. In this study, replica exchange
      molecular dynamics simulations were performed to investigate monomeric and
      dimeric states of PrP106-126 in implicit solvent. The structural diversity of
      PrP106-126 was observed and this peptide did not acquire stable structure. The
      dimeric PrP106-126 also displayed structural diversity and hydrophobic
      interaction drove the dimerization. To further study initial oligomerization of
      PrP106-126, 1 us conventional molecular dynamics simulations of trimer and
      tetramer formation were carried out in implicit solvent. We have observed the
      spontaneous formation of several basic oligomers and stable oligomers with high
      beta-sheet contents were sampled in the simulations of trimer and tetramer
      formation. The beta-hairpin formed in hydrophobic tail of PrP106-126 with
      residues 118-120 in turn may stabilize these oligomers and seed the formation
      oligomers. This study can provide insight into the detailed information about the
      structure of PrP106-126 and the dynamics of aggregation of monomeric PrP106-126
      into oligomers in atomic level. 

PMID- 24586267
TI  - Functional androdioecy in critically endangered Gymnocladus assamicus
      (Leguminosae) in the Eastern Himalayan Region of Northeast India.
AB  - Gymnocladus assamicus is a critically endangered tree species endemic to
      Northeast India, and shows sexual dimorphism with male and hermaphrodite flowers
      on separate trees. We studied phenology, reproductive biology and mating system
      of the species. The flowers are small, tubular, odorless and last for about 96
      hours. Pollen grains in both morphs were viable and capable of fertilization
      leading to fruit and seed set. Scanning electron micrographs revealed
      morphologically similar pollen in both male and hermaphrodite flowers. The fruit
      set in open pollinated flowers was 43.61 percent, while controlled autogamous and
      geitonogamous pollinations yielded 76.81 and 65.58 percent fruit set
      respectively. Xenogamous pollinations between male and hermaphrodite flowers
      resulted in 56.85 percent fruit set and pollinations between hermaphrodite
      flowers yielded 67.90 percent fruit set. This indicates a functionally
      androdioecious mating system and pollination limited fruit set in G. assamicus.
      Phylogenetic analyses of Gymnocladus and the sister genus Gleditsia are needed to
      assess if the androdioecious mating system in G. assamicus evolved from dioecy as
      a result of selection for hermaphrodites for reproductive assurance during
      colonization of pollination limited high altitude ecosystems. 

PMID- 24586264
TI  - Tempol, an intracellular antioxidant, inhibits tissue factor expression,
      attenuates dendritic cell function, and is partially protective in a murine model
      of cerebral malaria.
AB  - BACKGROUND: The role of intracellular radical oxygen species (ROS) in
      pathogenesis of cerebral malaria (CM) remains incompletely understood. METHODS
      AND FINDINGS: We undertook testing Tempol--a superoxide dismutase (SOD) mimetic
      and pleiotropic intracellular antioxidant--in cells relevant to malaria
      pathogenesis in the context of coagulation and inflammation. Tempol was also
      tested in a murine model of CM induced by Plasmodium berghei Anka infection.
      Tempol was found to prevent transcription and functional expression of
      procoagulant tissue factor in endothelial cells (ECs) stimulated by
      lipopolysaccharide (LPS). This effect was accompanied by inhibition of IL-6, IL
      8, and monocyte chemoattractant protein (MCP-1) production. Tempol also
      attenuated platelet aggregation and human promyelocytic leukemia HL60 cells
      oxidative burst. In dendritic cells, Tempol inhibited LPS-induced production of
      TNF-alpha, IL-6, and IL-12p70, downregulated expression of co-stimulatory
      molecules, and prevented antigen-dependent lymphocyte proliferation. Notably,
      Tempol (20 mg/kg) partially increased the survival of mice with CM.
      Mechanistically, treated mice had lowered plasma levels of MCP-1, suggesting that
      Tempol downmodulates EC function and vascular inflammation. Tempol also
      diminished blood brain barrier permeability associated with CM when started at
      day 4 post infection but not at day 1, suggesting that ROS production is tightly
      regulated. Other antioxidants-such as alpha-phenyl N-tertiary-butyl nitrone (PBN;
      a spin trap), MnTe-2-PyP and MnTBAP (Mn-phorphyrin), Mitoquinone (MitoQ) and
      Mitotempo (mitochondrial antioxidants), M30 (an iron chelator), and
      epigallocatechin gallate (EGCG; polyphenol from green tea) did not improve
      survival. By contrast, these compounds (except PBN) inhibited Plasmodium
      falciparum growth in culture with different IC50s. Knockout mice for SOD1 or
      phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (gp91(phox
      /-)) or mice treated with inhibitors of SOD (diethyldithiocarbamate) or NADPH
      oxidase (diphenyleneiodonium) did not show protection or exacerbation for CM.
      CONCLUSION: Results with Tempol suggest that intracellular ROS contribute, in
      part, to CM pathogenesis. Therapeutic targeting of intracellular ROS in CM is
      discussed.

PMID- 24586268
TI  - The miRNA plasma signature in response to acute aerobic exercise and endurance
      training.
AB  - MiRNAs are potent intracellular posttranscriptional regulators and are also
      selectively secreted into the circulation in a cell-specific fashion. Global
      changes in miRNA expression in skeletal muscle in response to endurance exercise
      training have been reported. Therefore, our aim was to establish the miRNA
      signature in human plasma in response to acute exercise and chronic endurance
      training by utilizing a novel methodological approach. RNA was isolated from
      human plasma collected from young healthy men before and after an acute endurance
      exercise bout and following 12 weeks of endurance training. Global miRNA (742
      miRNAs) measurements were performed as a screening to identify detectable miRNAs
      in plasma. Using customized qPCR panels we quantified the expression levels of
      miRNAs detected in the screening procedure (188 miRNAs). We demonstrate a dynamic
      regulation of circulating miRNA (ci-miRNA) levels following 0 hour (miR-106a, miR
      221, miR-30b, miR-151-5p, let-7i, miR-146, miR-652 and miR-151-3p), 1 hour (miR
      338-3p, miR-330-3p, miR-223, miR-139-5p and miR-143) and 3 hours (miR-1) after an
      acute exercise bout (P<0.00032). Where ci-miRNAs were all downregulated
      immediately after an acute exercise bout (0 hour) the 1 and 3 hour post exercise
      timepoints were followed by upregulations. In response to chronic training, we
      identified seven ci-miRNAs with decreased levels in plasma (miR-342-3p, let-7d,
      miR-766, miR-25, miR-148a, miR-185 and miR-21) and two miRNAs that were present
      at higher levels after the training period (miR-103 and miR-107) (P<0.00032). In
      conclusion, acute exercise and chronic endurance training, likely through
      specific mechanisms unique to each stimulus, robustly modify the miRNA signature
      of human plasma. 

PMID- 24586270
TI  - Mutual information between discrete and continuous data sets.
AB  - Mutual information (MI) is a powerful method for detecting relationships between
      data sets. There are accurate methods for estimating MI that avoid problems with
      "binning" when both data sets are discrete or when both data sets are continuous.
      We present an accurate, non-binning MI estimator for the case of one discrete
      data set and one continuous data set. This case applies when measuring, for
      example, the relationship between base sequence and gene expression level, or the
      effect of a cancer drug on patient survival time. We also show how our method can
      be adapted to calculate the Jensen-Shannon divergence of two or more data sets. 

PMID- 24586271
TI  - Cannabinoid neuromodulation in the adult early visual cortex.
AB  - Sensory processing is an active process involving the interaction of ongoing
      cortical activity with incoming stimulus information. However, the modulators and
      circuits involved in this interaction are incompletely understood. One potential
      candidate is the cannabinoid-signaling system, which is known to modulate the
      dynamics of cortical networks. Here, we show that in the primate primary and
      secondary visual cortices, the cannabinoid CP55940 modulates not only population
      dynamics but also influences the dynamics of the stimulus-response relationship
      of individual neurons. At the population level, CP55940 decreases EEG power, LFP
      power, and LFP coherence. At the single-neuron level, intrinsic spike train
      dynamics appear relatively unchanged, but visual receptive fields are altered:
      CP55940 induced an overall delay and broadening of the temporal component of V1
      and V2 spatiotemporal receptive fields. Our findings provide neurophysiologic
      evidence for a link between cannabinoid-signaling, network dynamics and the
      function of a canonical cortical circuit. 

PMID- 24586269
TI  - Anticancer compound plumbagin and its molecular targets: a structural insight
      into the inhibitory mechanisms using computational approaches.
AB  - Plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone) is a naphthoquinone derivative
      from the roots of plant Plumbago zeylanica and belongs to one of the largest and
      diverse groups of plant metabolites. The anticancer and antiproliferative
      activities of plumbagin have been observed in animal models as well as in cell
      cultures. Plumbagin exerts inhibitory effects on multiple cancer-signaling
      proteins, however, the binding mode and the molecular interactions have not yet
      been elucidated for most of these protein targets. The present study is the first
      attempt to provide structural insights into the binding mode of plumbagin to five
      cancer signaling proteins viz. PI3Kgamma, AKT1/PKBalpha, Bcl-2, NF-kappaB, and
      Stat3 using molecular docking and (un)binding simulation analysis. We validated
      plumbagin docking to these targets with previously known important residues. The
      study also identified and characterized various novel interacting residues of
      these targets which mediate the binding of plumbagin. Moreover, the exact modes
      of inhibition when multiple mode of inhibition existed was also shown. Results
      indicated that the engaging of these important interacting residues in plumbagin
      binding leads to inhibition of these cancer-signaling proteins which are key
      players in the pathogenesis of cancer and thereby ceases the progression of the
      disease. 

PMID- 24586272
TI  - Neurological and histological consequences induced by in vivo cerebral oxidative
      stress: evidence for beneficial effects of SRT1720, a sirtuin 1 activator, and
      sirtuin 1-mediated neuroprotective effects of poly(ADP-ribose) polymerase
      inhibition.
AB  - Poly(ADP-ribose)polymerase and sirtuin 1 are both NAD(+)-dependent enzymes. In
      vitro oxidative stress activates poly(ADP-ribose)polymerase, decreases NAD(+)
      level, sirtuin 1 activity and finally leads to cell death. Poly(ADP
      ribose)polymerase hyperactivation contributes to cell death. In addition,
      poly(ADP-ribose)polymerase inhibition restores NAD(+) level and sirtuin 1
      activity in vitro. In vitro sirtuin 1 induction protects neurons from cell loss
      induced by oxidative stress. In this context, the role of sirtuin 1 and its
      involvement in beneficial effects of poly(ADP-ribose)polymerase inhibition were
      evaluated in vivo in a model of cerebral oxidative stress induced by
      intrastriatal infusion of malonate in rat. Malonate promoted a NAD(+) decrease
      that was not prevented by 3-aminobenzamide, a poly(ADP-ribose)polymerase
      inhibitor, at 4 and 24 hours. However, 3-aminobenzamide increased nuclear SIRT1
      activity/expression ratio after oxidative stress. Malonate induced a neurological
      deficit associated with a striatal lesion. Both were reduced by 3-aminobenzamide
      and SRT1720, a sirtuin 1 activator, showing beneficial effects of poly(ADP
      ribose)polymerase inhibition and sirtuin 1 activation on oxidative stress
      consequences. EX527, a sirtuin 1 inhibitor, given alone, modified neither the
      score nor the lesion, suggesting that endogenous sirtuin 1 was not activated
      during cerebral oxidative stress. However, its association with 3-aminobenzamide
      suppressed the neurological improvement and the lesion reduction induced by 3
      aminobenzamide. The association of 3-aminobenzamide with SRT1720, the sirtuin 1
      activator, did not lead to a better protection than 3-aminobenzamide alone. The
      present data represent the first demonstration that the sirtuin 1 activator
      SRT1720 is neuroprotective during in vivo cerebral oxidative stress. Furthermore
      sirtuin 1 activation is involved in the beneficial effects of poly(ADP
      ribose)polymerase inhibition after in vivo cerebral oxidative stress. 

PMID- 24586273
TI  - Physiological characterisation of human iPS-derived dopaminergic neurons.
AB  - Human induced pluripotent stem cells (hiPSCs) offer the potential to study
      otherwise inaccessible cell types. Critical to this is the directed
      differentiation of hiPSCs into functional cell lineages. This is of particular
      relevance to research into neurological disease, such as Parkinson's disease
      (PD), in which midbrain dopaminergic neurons degenerate during disease
      progression but are unobtainable until post-mortem. Here we report a detailed
      study into the physiological maturation over time of human dopaminergic neurons
      in vitro. We first generated and differentiated hiPSC lines into midbrain
      dopaminergic neurons and performed a comprehensive characterisation to confirm
      dopaminergic functionality by demonstrating dopamine synthesis, release, and re
      uptake. The neuronal cultures include cells positive for both tyrosine
      hydroxylase (TH) and G protein-activated inward rectifier potassium channel 2
      (Kir3.2, henceforth referred to as GIRK2), representative of the A9 population of
      substantia nigra pars compacta (SNc) neurons vulnerable in PD. We observed for
      the first time the maturation of the slow autonomous pace-making (<10 Hz) and
      spontaneous synaptic activity typical of mature SNc dopaminergic neurons using a
      combination of calcium imaging and electrophysiology. hiPSC-derived neurons
      exhibited inositol tri-phosphate (IP3) receptor-dependent release of
      intracellular calcium from the endoplasmic reticulum in neuronal processes as
      calcium waves propagating from apical and distal dendrites, and in the soma.
      Finally, neurons were susceptible to the dopamine neuron-specific toxin 1-methyl
      4-phenylpyridinium (MPP+) which reduced mitochondrial membrane potential and
      altered mitochondrial morphology. Mature hiPSC-derived dopaminergic neurons
      provide a neurophysiologically-defined model of previously inaccessible
      vulnerable SNc dopaminergic neurons to bridge the gap between clinical PD and
      animal models. 

PMID- 24586275
TI  - Lovastatin delays infection and increases survival rates in AG129 mice infected
      with dengue virus serotype 2.
AB  - BACKGROUND: It has been reported that treatment of DENV-infected cultures with
      Lovastatin (LOV), can affect viral assembly. The objective of this study was to
      evaluate the effect of LOV on the survival rate and viremia levels of DENV-2
      infected AG129 mice. METHODOLOGY/PRINCIPAL FINDINGS: Mice were inoculated with 1
      * 10(6) plaque-forming units (PFU/ml) of DENV-2 and treated with LOV (200
      mg/kg/day). Pre-treatment with one or three doses of LOV increased the survival
      rate compared to untreated mice (7.3 and 7.1 days, respectively, compared to 4.8
      days). Viremia levels also decreased by 21.8% compared to untreated mice, but
      only in the group administered three doses prior to inoculation. When LOV was
      administered after viral inoculation, the survival rate increased (7.3 days in
      the group treated at 24 hpi, 6.8 days in the group treated at 48 hpi and 6.5 days
      in the group treated with two doses) compared to the untreated group (4.8 days).
      Interestingly, the serum viral titer increased by 24.6% in mice treated at 48 hpi
      with a single dose of LOV and by 21.7% in mice treated with two doses (at 24 and
      48 hpi) of LOV compared to untreated mice. Finally histopathological changes in
      the liver and spleen in infected and untreated mice included massive
      extramedullary erythropoiesis foci and inflammatory filtration, and these
      characteristics were decreased or absent in LOV-treated mice.
      CONCLUSIONS/SIGNIFICANCE: Our results suggest that the effect of LOV on viremia
      depends on the timing of treatment and on the number of doses administered. We
      observed a significant increase in the survival rate in both schemes due to a
      delay in the progression of the disease. However, the results obtained in the
      post-treatment scheme must be handled carefully because this treatment scheme
      increases viremia and we do not know how this increase could affect disease
      progression in humans.

PMID- 24586274
TI  - Ultraweak photon emission as a non-invasive health assessment: a systematic
      review.
AB  - We conducted a systematic review (SR) of the peer reviewed scientific literature
      on ultraweak photon emissions (UPE) from humans. The question was: Can ultraweak
      photon emissions from humans be used as a non-invasive health assessment? A
      systematic search was conducted across eight relevant databases: PubMed/MEDLINE,
      BIOSIS, CINAHL, PSYCHINFO, All of Cochrane EBM databases, GIDEON, DoD Biomedical
      Research, and clinicaltrials.gov from database inception to October 2011. Of the
      1315 studies captured by the search strategy, 56 met the inclusion criteria, out
      of which 1 was a RCT, 27 were CCT, and 28 were observational and descriptive
      studies. There were no systematic reviews/meta-analyses that fit the inclusion
      criteria. In this report, the authors provide an assessment of the quality of the
      RCT included; describe the characteristics of all the included studies, the
      outcomes assessed, and the effectiveness of photon emission as a potential health
      assessment tool. This report demonstrates that the peer reviewed literature on
      UPE and human UPE measurement in particular is surprisingly large. Most of the
      human UPE literature is of good to high quality based on our systematic
      evaluation. However, an evaluation tool for systematically evaluating this type
      of "bio-evaluation" methodology is not currently available and would be worth
      developing. Publications in the peer reviewed literature over the last 50 years
      demonstrate that the use of "off-the-shelf" technologies and well described
      methodologies for the detection of human photon emissions are being used on a
      regular basis in medical and research settings. The overall quality of this
      literature is good and the use of this approach for determining inflammatory and
      oxidative states of patients indicate the growing use and value of this approach
      as both a medical and research tool. 

PMID- 24586276
TI  - The effects of intracranial pressure monitoring in patients with traumatic brain
      injury.
AB  - BACKGROUND: Although international guideline recommended routine intracranial
      pressure (ICP) monitoring for patients with severe traumatic brain injury(TBI),
      there were conflicting outcomes attributable to ICP monitoring according to the
      published studies. Hence, we conducted a meta-analysis to evaluate the efficacy
      and safety of ICP monitoring in patients with TBI. METHODS: Based on previous
      reviews, PubMed and two Chinese databases (Wangfang and VIP) were further
      searched to identify eligible studies. The primary outcome was mortality.
      Secondary outcomes included unfavourable outcome, adverse events, length of ICU
      stay and length of hospital stay. Weighted mean difference (WMD), odds ratio (OR)
      and 95% confidence intervals (CIs) were calculated and pooled using fixed-effects
      or random-effects model. RESULTS: two randomized controlled trials (RCTs) and
      seven cohort studies involving 11,038 patients met the inclusion criteria. ICP
      monitoring was not associated with a significant reduction in mortality (OR,
      1.16; 95% CI, 0.87-1.54), with substantial heterogeneity (I(2) = 80%, P<0.00001),
      which was verified by the sensitivity analyses. No significant difference was
      found in the occurrence of unfavourable outcome (OR, 1.40; 95% CI, 0.99-1.98;
      I(2) = 4%, P = 0.35) and adverse events (OR, 1.04; 95% CI, 0.64-1.70; I(2) = 78%,
      P = 0.03). However, we should be cautious to the result of adverse events because
      of the substantial heterogeneity in the comparison. Furthermore, longer ICU and
      hospital stay were the consistent tendency according to the pooled studies.
      CONCLUSIONS: No benefit was found in patients with TBI who underwent ICP
      monitoring. Considering substantial clinical heterogeneity, further large sample
      size RCTs are needed to confirm the current findings.

PMID- 24586277
TI  - Increased constituent ratios of Klebsiella sp., Acinetobacter sp., and
      Streptococcus sp. and a decrease in microflora diversity may be indicators of
      ventilator-associated pneumonia: a prospective study in the respiratory tracts of
      neonates.
AB  - Ventilator-associated pneumonia (VAP) is a common complication and cause of death
      in neonates on mechanical ventilation. However, it is difficult to define the
      causes of VAP. To understand the causes of VAP, we undertook a prospective study
      based on the diversity of the microflora in VAP. The experimental group consisted
      of newborns who suffered from respiratory distress syndrome (RDS) and VAP, while
      the control group suffered from RDS without VAP. Sputa were collected within 1,
      3, and 5 days of ventilation and were divided into six groups. DNA was extracted
      from the samples, and the 16S rDNA was PCR amplified, separated using denaturing
      gradient gel electrophoresis (DGGE), cloned and sequenced. The resulting
      sequences were compared using BLAST. The DGGE pictures were measured, and the
      richness, Shannon-Wiener index, and cluster maps were analyzed. No differences
      were found regarding the constituent ratio of any genus between the Non-VAP and
      VAP group within 1 day after intubation. After 1 to 3 days, the constituent
      ratios of Klebsiella sp., Acinetobacter sp., and Streptococcus sp. in the VAP
      group were higher than those in the Non-VAP group, and the ratios of Serratia sp.
      and Achromobacter sp. were lower. After 3 to 5 days, the ratios of Klebsiella
      sp., Acinetobacter sp., Serratia sp., and Achromobacter sp. were lower than those
      in the Non-VAP group. The richness and Shannon-Wiener index of the Non-VAP group
      were higher than those of the VAP group from 1 to 3 days after intubation, while
      no differences were found within 1 day and from 3 to 5 days. We conclude that
      during the first three days of intubation, the microflora diversity in the lower
      respiratory tract was reduced due to VAP, and the greater constituent ratios of
      Klebsiella sp., Acinetobacter sp., and Streptococcus sp. in the sputum may be
      indicators of VAP. 

PMID- 24586278
TI  - Associations between disaster exposures, peritraumatic distress, and
      posttraumatic stress responses in Fukushima nuclear plant workers following the
      2011 nuclear accident: the Fukushima NEWS Project study.
AB  - BACKGROUND: The 2011 Fukushima Daiichi Nuclear Power Plant accident was the worst
      nuclear disaster since Chernobyl. The nearby Daini plant also experienced
      substantial damage but remained intact. Workers for the both plants experienced
      multiple stressors as disaster victims and workers, as well as the criticism from
      the public due to their company's post-disaster management. Little is known about
      the psychological pathway mechanism from nuclear disaster exposures, distress
      during and immediately after the event (peritraumatic distress; PD), to
      posttraumatic stress responses (PTSR). METHODS: A self-report questionnaire was
      administered to 1,411 plant employees (Daiichi, n = 831; Daini, n = 580) 2-3
      months post-disaster (total response rate: 80.2%). The socio-demographic
      characteristics and disaster-related experiences were assessed as independent
      variables. PD and PTSR were measured by the Japanese versions of Peritraumatic
      Distress Inventory and the Impact of Event Scale-Revised, respectively. The
      analysis was conducted separately for the two groups. Bivariate regression
      analyses were performed to assess the relationships between independent
      variables, PD, and PTSR. Significant variables were subsequently entered in the
      multiple regression analyses to explore the pathway mechanism for development of
      PTSR. RESULTS: For both groups, PTSR highly associated with PD (Daiichi: adjusted
      beta, 0.66; p<0.001; vs. Daini: adjusted beta, 0.67; p<0.001). PTSR also
      associated with discrimination/slurs experience (Daiichi: 0.11; p<0.001; vs.
      Daini, 0.09; p = 0.005) and presence of preexisting illness(es) (Daiichi: 0.07; p
      = 0.005; vs. Daini: 0.15; p<.0001). Other disaster-related variables were likely
      to be associated with PD than PTSR. CONCLUSION: Among the Fukushima nuclear plant
      workers, disaster exposures associated with PD. PTSR was highly affected by PD
      along with discrimination/slurs experience.

PMID- 24586279
TI  - Broad-scale climate influences on spring-spawning herring (Clupea harengus, L.)
      recruitment in the Western Baltic Sea.
AB  - Climate forcing in complex ecosystems can have profound implications for
      ecosystem sustainability and may thus challenge a precautionary ecosystem
      management. Climatic influences documented to affect various ecological functions
      on a global scale, may themselves be observed on quantitative or qualitative
      scales including regime shifts in complex marine ecosystems. This study
      investigates the potential climatic impact on the reproduction success of spring
      spawning herring (Clupea harengus) in the Western Baltic Sea (WBSS herring). To
      test for climate effects on reproduction success, the regionally determined and
      scientifically well-documented spawning grounds of WBSS herring represent an
      ideal model system. Climate effects on herring reproduction were investigated
      using two global indices of atmospheric variability and sea surface temperature,
      represented by the North Atlantic Oscillation (NAO) and the Atlantic Multi
      decadal Oscillation (AMO), respectively, and the Baltic Sea Index (BSI) which is
      a regional-scale atmospheric index for the Baltic Sea. Moreover, we combined a
      traditional approach with modern time series analysis based on a recruitment
      model connecting parental population components with reproduction success.
      Generalized transfer functions (ARIMAX models) allowed evaluating the dynamic
      nature of exogenous climate processes interacting with the endogenous recruitment
      process. Using different model selection criteria our results reveal that in
      contrast to NAO and AMO, the BSI shows a significant positive but delayed signal
      on the annual dynamics of herring recruitment. The westward influence of the
      Siberian high is considered strongly suppressing the influence of the NAO in this
      area leading to a higher explanatory power of the BSI reflecting the atmospheric
      pressure regime on a North-South transect between Oslo, Norway and Szczecin,
      Poland. We suggest incorporating climate-induced effects into stock and risk
      assessments and management strategies as part of the EU ecosystem approach to
      support sustainable herring fisheries in the Western Baltic Sea. 

PMID- 24586280
TI  - A glucose-utilizing strain, Cupriavidus euthrophus B-10646: growth kinetics,
      characterization and synthesis of multicomponent PHAs.
AB  - This study investigates kinetic and production parameters of a glucose-utilizing
      bacterial strain, C. eutrophus B-10646, and its ability to synthesize PHA
      terpolymers. Optimization of a number of parameters of bacterial culture (cell
      concentration in the inoculum, physiological activity of the inoculum, determined
      by the initial intracellular polymer content, and glucose concentration in the
      culture medium during cultivation) provided cell concentrations and PHA yields
      reaching 110 g/L and 80%, respectively, under two-stage batch culture conditions.
      Addition of precursor substrates (valerate, hexanoate, propionate, gamma
      butyrolactone) to the culture medium enabled synthesis of PHA terpolymers,
      P(3HB/3HV/4HB) and P(3HB/3HV/3HHx), with different composition and different
      molar fractions of 3HB, 3HV, 4HB, and 3HHx. Different types of PHA terpolymers
      synthesized by C. eutrophus B-10646 were used to prepare films, whose
      physicochemical and physical-mechanical properties were investigated. The
      properties of PHA terpolymers were significantly different from those of the P3HB
      homopolymer: they had much lower degrees of crystallinity and lower melting
      points and thermal decomposition temperatures, with the difference between these
      temperatures remaining practically unchanged. Films prepared from all PHA
      terpolymers had higher mechanical strength and elasticity than P3HB films. In
      spite of dissimilar surface structures, all films prepared from PHA terpolymers
      facilitated attachment and proliferation of mouse fibroblast NIH 3T3 cells more
      effectively than polystyrene and the highly crystalline P3HB. 

PMID- 24586281
TI  - A descriptive model of patient readiness, motivators, and hepatitis C treatment
      uptake among Australian prisoners.
AB  - BACKGROUND: Hepatitis C virus infection (HCV) has a significant global health
      burden with an estimated 2%-3% of the world's population infected, and more than
      350,000 dying annually from HCV-related conditions including liver failure and
      liver cancer. Prisons potentially offer a relatively stable environment in which
      to commence treatment as they usually provide good access to health care
      providers, and are organised around routine and structure. Uptake of treatment of
      HCV, however, remains low in the community and in prisons. In this study, we
      explored factors affecting treatment uptake inside prisons and hypothesised that
      prisoners have unique issues influencing HCV treatment uptake as a consequence of
      their incarceration which are not experienced in other populations. METHOD AND
      FINDINGS: We undertook a qualitative study exploring prisoners' accounts of why
      they refused, deferred, delayed or discontinued HCV treatment in prison. Between
      2010 and 2013, 116 Australian inmates were interviewed from prisons in New South
      Wales, Queensland, and Western Australia. Prisoners experienced many factors
      similar to those which influence treatment uptake of those living with HCV
      infection in the community. Incarceration, however, provides different
      circumstances of how these factors are experienced which need to be better
      understood if the number of prisoners receiving treatment is to be increased. We
      developed a descriptive model of patient readiness and motivators for HCV
      treatment inside prisons and discussed how we can improve treatment uptake among
      prisoners. CONCLUSION: This study identified a broad and unique range of
      challenges to treatment of HCV in prison. Some of these are likely to be
      diminished by improving treatment options and improved models of health care
      delivery. Other barriers relate to inmate understanding of their illness and
      stigmatisation by other inmates and custodial staff and generally appear less
      amenable to change although there is potential for peer-based education to
      address lack of knowledge and stigma.

PMID- 24586282
TI  - Comprehensive transcriptome analysis of developing xylem responding to artificial
      bending and gravitational stimuli in Betula platyphylla.
AB  - Betula platyphylla Suk (birch) is a fast-growing woody species that is important
      in pulp industries and the biofuels. However, as an important pulp species, few
      studies had been performed on its wood formation. In the present study, we
      investigated the molecular responses of birch xylem to artificial bending and
      gravitational stimuli. After trunks of birch trees were subjected to bending for
      8 weeks, the cellulose content was significantly greater in tension wood (TW)
      than in opposite wood (OW) or normal wood (NW), whereas the lignin content in TW
      was significantly lower than that in OW and NW. In addition, TW grew more rapidly
      than OW and generated TW-specific fibers with an additional G-layer. Three
      transcriptome libraries were constructed from TW, OW and NW of B. platyphylla,
      respectively, after the plants were subjected to artificial bending. Overall,
      80,909 nonredundant unigenes with a mean size of 768 nt were assembled.
      Expression profiles were generated, and 9,684 genes were found to be
      significantly differentially expressed among the TW, OW and NW libraries. These
      included genes involved in secondary cell wall structure, wood composition, and
      cellulose or lignin biosynthesis. Our study showed that during TW formation,
      genes involved in cellulose synthesis were induced, while the expression of
      lignin synthesis-related genes decreased, resulting in increased cellulose
      content and decreased lignin levels in TW. In addition, fasciclin-like
      arabinogalactan proteins play important role in TW formation. These findings may
      provide important insights into wood formation at the molecular level. 

PMID- 24586283
TI  - Isolation and molecular characterization of a novel picornavirus from baitfish in
      the USA.
AB  - During both regulatory and routine surveillance sampling of baitfish from the
      states of Illinois, Minnesota, Montana, and Wisconsin, USA, isolates (n = 20) of
      a previously unknown picornavirus were obtained from kidney/spleen or entire
      viscera of fathead minnows (Pimephales promelas) and brassy minnows (Hybognathus
      hankinsoni). Following the appearance of a diffuse cytopathic effect, examination
      of cell culture supernatant by negative contrast electron microscopy revealed the
      presence of small, round virus particles (~ 30-32 nm), with picornavirus-like
      morphology. Amplification and sequence analysis of viral RNA identified the agent
      as a novel member of the Picornaviridae family, tentatively named fathead minnow
      picornavirus (FHMPV). The full FHMPV genome consisted of 7834 nucleotides.
      Phylogenetic analysis based on 491 amino acid residues of the 3D gene showed
      98.6% to 100% identity among the 20 isolates of FHMPV compared in this study
      while only 49.5% identity with its nearest neighbor, the bluegill picornavirus
      (BGPV) isolated from bluegill (Lepomis macrochirus). Based on complete
      polyprotein analysis, the FHMPV shared 58% (P1), 33% (P2) and 43% (P3) amino acid
      identities with BGPV and shared less than 40% amino acid identity with all other
      picornaviruses. Hence, we propose the creation of a new genus (Piscevirus) within
      the Picornaviridae family. The impact of FHMPV on the health of fish populations
      is unknown at present.

PMID- 24586284
TI  - Colonic miRNA expression/secretion, regulated by intestinal epithelial PepT1,
      plays an important role in cell-to-cell communication during colitis.
AB  - PepT1 is a member of the proton-oligopeptide cotransporter family SLC15, which
      mediates the transport of di/tripeptides from intestinal lumen into epithelial
      cells. MicroRNAs (miRNAs), a small noncoding RNAs (21-23 nucleotides), post
      transcriptionally regulate gene expression by binding to the 3'-untranslated
      regions (UTRs) of their target mRNAs. Although the role of most miRNAs remains
      elusive, they have been implicated in vital cellular functions such as intestinal
      epithelial cells differentiation, proliferation, and apoptosis. In the present
      study, we investigated the effect of intestinal epithelial PepT1 expression on
      microRNA (miRNA) expression/secretion in the colons of control mice and in mice
      with experimentally induced colonic inflammation (colitis). The colonic miRNA
      expression was deregulated in both colitis and control mice but the deregulation
      of miRNA expression/secretion was specific to colonic tissue and did not affect
      other tissues such as spleen and liver. Intestinal epithelial PepT1-dependent
      deregulation of colonic miRNA expression not only affects epithelial cells but
      also other cell types, such as intestinal macrophages. Importantly, we found the
      miRNA 23b which was known to be involved in inflammatory bowel disease was
      secreted and transported between cells to impose a gene-silencing effect on
      recipient intestinal macrophages. Based on our data, we may conclude that the
      expression of a specific protein, PepT1, in the intestine affects local miRNA
      expression/secretion in the colon on a tissue specific manner and may play an
      important role during the induction and progression of colitis. Colonic miRNA
      expression/secretion, regulated by intestinal epithelial PepT1, could play a
      crucial role in cell-to-cell communication during colitis. 

PMID- 24586286
TI  - In their own words: treating very young BRCA1/2 mutation-positive women with care
      and caution.
AB  - PURPOSE: Young women who have been identified as carrying a deleterious mutation
      in BRCA1 or BRCA2 face a unique set of challenges related to managing cancer risk
      during a demographically-dense stage of life. They may struggle with decision
      making in the absence of clear age-specific guidelines for medical management and
      because they have not yet fully developed the capacity to make life-altering
      decisions confidently. This study sought a patient-centered perspective on the
      dilemmas faced by 18-24 year olds who completed BRCA1/2 gene mutation testing
      prior to their 25(th) birthdays. PATIENTS AND METHOD: This study integrated
      qualitative data from three independent investigations of BRCA1/2-positive women
      recruited through cancer risk clinics, hospital-based research centers, and
      online organizations. All 32 participants were women aged 21-25 who tested
      positive for a BRCA1/2 gene mutation between 2 and 60 months prior to data
      collection. Investigators used techniques of grounded theory and interpretive
      description to conduct both within and cross-study analysis. RESULTS:
      Participants expressed needs for (1) greater clarity in recommendations for
      screening and prevention before age 25, especially with consideration of early
      and regular exposure to radiation associated with mammography or to hormones used
      in birth control, and (2) ongoing contact with providers to discuss risk
      management protocols as they become available. CONCLUSIONS: Health care needs
      during the young adult years evolve with the cognitive capacity to address abrupt
      and pressing change. Specific needs of women in this population include a desire
      to balance autonomous decision-making with supportive guidance, a need for clear,
      accurate and consistent medical recommendations. Optimally, these women are best
      cared for by a team of genetically-oriented providers as part of a sustained
      program of ongoing support, rather than seen in an episodic, crisis-driven
      fashion. A discussion of insurance issues and provider-patient cultural
      differences is presented.

PMID- 24586287
TI  - Systematic review of evidence-based guidelines on medication therapy for upper
      respiratory tract infection in children with AGREE instrument.
AB  - OBJECTIVES: To summarize recommendations of existing guidelines on the treatment
      of upper respiratory tract infections (URTIs) in children, and to assess the
      methodological quality of these guidelines. METHODS: We searched seven databases
      and web sites of relevant academic agencies. Evidence-based guidelines on
      pediatric URTIs were included. AGREE II was used to assess the quality of these
      guidelines. Two researchers selected guidelines independently and extracted
      information on publication years, institutions, target populations,
      recommendations, quality of evidence, and strength of recommendations. We
      compared the similarities and differences of recommendations and their strength.
      We also analyzed the reasons for variation. RESULTS: Thirteen guidelines meeting
      our inclusion criteria were included. Huge differences existed among these 13
      guidelines concerning the categorization of evidence and recommendations. Nearly
      all of these guidelines lacked the sufficient involvement of stake holders.
      Further, the applicability of these guidelines still needs to be improved. In
      terms of recommendations, penicillin and amoxicillin were suggested for group A
      streptococcal pharyngitis. Amoxicillin and amoxicillin-clavulanate were
      recommended for acute bacterial rhinosinusitis (ABRS). An observation of 2-3 days
      prior to antibiotic therapy initiation for mild acute otitis media (AOM) was
      recommended with amoxicillin as the suggested first choice agent. Direct evidence
      to support strong recommendations on the therapy for influenza is still lacking.
      In addition, the antimicrobial durations for pharyngitis and ABRS were still
      controversial. No consensus was reached for the onset of antibiotics for ABRS in
      children. CONCLUSIONS: Future guidelines should use a consistent grading system
      for the quality of evidence and strength of recommendations. More effort needs to
      be paid to seek the preference of stake holders and to improve the applicability
      of guidelines. Further, there are still areas in pediatric URTIs that need more
      research.

PMID- 24586285
TI  - Granger causality network reconstruction of conductance-based integrate-and-fire
      neuronal systems.
AB  - Reconstruction of anatomical connectivity from measured dynamical activities of
      coupled neurons is one of the fundamental issues in the understanding of
      structure-function relationship of neuronal circuitry. Many approaches have been
      developed to address this issue based on either electrical or metabolic data
      observed in experiment. The Granger causality (GC) analysis remains one of the
      major approaches to explore the dynamical causal connectivity among individual
      neurons or neuronal populations. However, it is yet to be clarified how such
      causal connectivity, i.e., the GC connectivity, can be mapped to the underlying
      anatomical connectivity in neuronal networks. We perform the GC analysis on the
      conductance-based integrate-and-fire (I&F) neuronal networks to obtain their
      causal connectivity. Through numerical experiments, we find that the underlying
      synaptic connectivity amongst individual neurons or subnetworks, can be
      successfully reconstructed by the GC connectivity constructed from voltage time
      series. Furthermore, this reconstruction is insensitive to dynamical regimes and
      can be achieved without perturbing systems and prior knowledge of neuronal model
      parameters. Surprisingly, the synaptic connectivity can even be reconstructed by
      merely knowing the raster of systems, i.e., spike timing of neurons. Using spike
      triggered correlation techniques, we establish a direct mapping between the
      causal connectivity and the synaptic connectivity for the conductance-based I&F
      neuronal networks, and show the GC is quadratically related to the coupling
      strength. The theoretical approach we develop here may provide a framework for
      examining the validity of the GC analysis in other settings.

PMID- 24586288
TI  - Strains and stressors: an analysis of touchscreen learning in genetically diverse
      mouse strains.
AB  - Touchscreen-based systems are growing in popularity as a tractable, translational
      approach for studying learning and cognition in rodents. However, while mouse
      strains are well known to differ in learning across various settings, performance
      variation between strains in touchscreen learning has not been well described.
      The selection of appropriate genetic strains and backgrounds is critical to the
      design of touchscreen-based studies and provides a basis for elucidating genetic
      factors moderating behavior. Here we provide a quantitative foundation for visual
      discrimination and reversal learning using touchscreen assays across a total of
      35 genotypes. We found significant differences in operant performance and
      learning, including faster reversal learning in DBA/2J compared to C57BL/6J mice.
      We then assessed DBA/2J and C57BL/6J for differential sensitivity to an
      environmental insult by testing for alterations in reversal learning following
      exposure to repeated swim stress. Stress facilitated reversal learning
      (selectively during the late stage of reversal) in C57BL/6J, but did not affect
      learning in DBA/2J. To dissect genetic factors underlying these differences, we
      phenotyped a family of 27 BXD strains generated by crossing C57BL/6J and DBA/2J.
      There was marked variation in discrimination, reversal and extinction learning
      across the BXD strains, suggesting this task may be useful for identifying
      underlying genetic differences. Moreover, different measures of touchscreen
      learning were only modestly correlated in the BXD strains, indicating that these
      processes are comparatively independent at both genetic and phenotypic levels.
      Finally, we examined the behavioral structure of learning via principal component
      analysis of the current data, plus an archival dataset, totaling 765 mice. This
      revealed 5 independent factors suggestive of "reversal learning," "motivation
      related late reversal learning," "discrimination learning," "speed to respond,"
      and "motivation during discrimination." Together, these findings provide a
      valuable reference to inform the choice of strains and genetic backgrounds in
      future studies using touchscreen-based tasks. 

PMID- 24586289
TI  - Degeneration modulates retinal response to transient exogenous oxidative injury.
AB  - PURPOSE: Oxidative injury is involved in retinal and macular degeneration. We aim
      to assess if retinal degeneration associated with genetic defect modulates the
      retinal threshold for encountering additional oxidative challenges. METHODS:
      Retinal oxidative injury was induced in degenerating retinas (rd10) and in
      control mice (WT) by intravitreal injections of paraquat (PQ). Retinal function
      and structure was evaluated by electroretinogram (ERG) and histology,
      respectively. Oxidative injury was assessed by immunohistochemistry for 4-Hydroxy
      2-nonenal (HNE), and by Thiobarbituric Acid Reactive Substances (TBARS) and
      protein carbonyl content (PCC) assays. Anti-oxidant mechanism was assessed by
      quantitative real time PCR (QPCR) for mRNA of antioxidant genes and genes related
      to iron metabolism, and by catalase activity assay. RESULTS: Three days following
      PQ injections (1 ul of 0.25, 0.75, and 2 mM) the average ERG amplitudes decreased
      more in the WT mice compared with the rd10 mice. For example, following 2 mM PQ
      injection, ERG amplitudes reduced 1.84-fold more in WT compared with rd10 mice (p
      = 0.02). Injection of 4 mM PQ resulted in retinal destruction. Altered retina
      morphology associated with PQ was substantially more severe in WT eyes compared
      with rd10 eyes. Oxidative injury according to HNE staining and TBARS assay
      increased 1.3-fold and 2.1-fold more, respectively, in WT compared with rd10
      mice. At baseline, prior to PQ injection, mRNA levels of antioxidant genes
      (Superoxide Dismutase1, Glutathione Peroxidase1, Catalase) and of Transferrin
      measured by quantitative PCR were 2.1-7.8-fold higher in rd10 compared with WT
      mice (p<0.01 each), and catalase activity was 1.7-fold higher in rd10 (p =
      0.0006). CONCLUSIONS: This data suggests that degenerating rd10 retinas encounter
      a relatively lower degree of damage in response to oxidative injury compared with
      normal retinas. Constitutive up-regulation of the oxidative defense mechanism in
      degenerating retinas may confer such relative protection from oxidative injury.

PMID- 24586291
TI  - N-acetyltransferase 2 polymorphisms and risk of esophageal cancer in a Chinese
      population.
AB  - Esophageal cancer was the fifth most commonly diagnosed cancer and the fourth
      leading cause of cancer-related death in China in 2009. Genetic factors might
      play an important role in the carcinogenesis of esophageal squamous cell
      carcinoma (ESCC). We conducted a hospital-based case-control study to evaluate
      ten NAT2 tagging single nucleotide polymorphisms (SNPs) on the risk of ESCC. Six
      hundred and twenty-nine ESCC cases and 686 controls were recruited. Their
      genotypes were determined using the ligation detection reaction method. In the
      single locus analyses, there was a borderline statistically significant
      difference in genotype frequencies of NAT2 rs1565684 T>C SNP between the cases
      and the controls (p = 0.057). The NAT2 rs1565684 CC genotype was associated with
      a borderline significantly increased risk for ESCC (CC vs. TT: adjusted OR =
      1.77, 95% CI = 0.97-3.21, p = 0.063 and CC vs. TT/TC: adjusted OR = 1.68, 95% CI
      = 0.93-3.04, p = 0.085). The association was evident among older patients and
      patients who never drunk. After the Bonferroni correction, in all comparison
      models, NAT2 rs1565684 T>C SNP was not associated with ESCC risk (p>0.05). For
      the other nine NAT2 SNPs, after Bonferroni correction, in all comparison models,
      the nine SNPs were also not associated with ESCC risk (p>0.05). Thus, nine NAT2
      tagging SNPs were not associated with risk of ESCC. NAT2 rs1565684 T>C SNP might
      play a slight role in ESCC etiology. Additional, larger studies and tissue
      specific biological characterization are required to confirm the current
      findings. 

PMID- 24586292
TI  - Disrupted intestinal microbiota and intestinal inflammation in children with
      cystic fibrosis and its restoration with Lactobacillus GG: a randomised clinical
      trial.
AB  - BACKGROUND & AIMS: Intestinal inflammation is a hallmark of cystic fibrosis (CF).
      Administration of probiotics can reduce intestinal inflammation and the incidence
      of pulmonary exacerbations. We investigated the composition of intestinal
      microbiota in children with CF and analyzed its relationship with intestinal
      inflammation. We also investigated the microflora structure before and after
      Lactobacillus GG (LGG) administration in children with CF with and without
      antibiotic treatment. METHODS: The intestinal microbiota were analyzed by
      denaturing gradient gel electrophoresis (DGGE), real-time polymerase chain
      reaction (RT-PCR), and fluorescence in situ hybridization (FISH). Intestinal
      inflammation was assessed by measuring fecal calprotectin (CLP) and rectal nitric
      oxide (rNO) production in children with CF as compared with healthy controls. We
      then carried out a small double-blind randomized clinical trial with LGG.
      RESULTS: Twenty-two children with CF children were enrolled in the study (median
      age, 7 years; range, 2-9 years). Fecal CLP and rNO levels were higher in children
      with CF than in healthy controls (184+/-146 ug/g vs. 52+/-46 ug/g; 18+/-15 vs.
      2.6+/-1.2 umol/L NO2 (-), respectively; P<0.01). Compared with healthy controls,
      children with CF had significantly different intestinal microbial core
      structures. The levels of Eubacterium rectale, Bacteroides uniformis, Bacteroides
      vulgatus, Bifidobacterium adolescentis, Bifidobacterium catenulatum, and
      Faecalibacterium prausnitzii were reduced in children with CF. A similar but more
      extreme pattern was observed in children with CF who were taking antibiotics. LGG
      administration reduced fecal CLP and partially restored intestinal microbiota.
      There was a significant correlation between reduced microbial richness and
      intestinal inflammation. CONCLUSIONS: CF causes qualitative and quantitative
      changes in intestinal microbiota, which may represent a novel therapeutic target
      in the treatment of CF. Administration of probiotics restored gut microbiota,
      supporting the efficacy of probiotics in reducing intestinal inflammation and
      pulmonary exacerbations. TRIAL REGISTRATION: ClinicalTrials.gov NCT 01961661.

PMID- 24586290
TI  - Sleep-wake cycle in young and older persons with a lifetime history of mood
      disorders.
AB  - Considering the marked changes in sleep and circadian rhythms across the
      lifespan, age may contribute to the heterogeneity in sleep-wake profiles linked
      to mood disorders. This study aimed to investigate the contributions of age and
      depression severity to sleep-wake disturbances. The Hamilton Depression Rating
      Scale (HDRS) was administered to assess current symptoms severity in 238 persons
      with a history of a mood disorder between 12 and 90 years of age (y.o.).
      Actigraphy was recorded over five to 22 days. Regression analyses and analyses of
      variance [age (12-19 y.o., 20-39 y.o., 40-59 y.o., and >= 60 y.o.) by depression
      severity (HDRS< and >= 8)] were conducted. The 12-19 y.o. and 20-39 y.o. groups
      had a delayed sleep schedule and acrophase compared to all other groups. The >=
      60 y.o. group had a lower rhythmicity and amplitude (p <= .006) than the 12-19
      y.o. group (p <= .046). Participants with a HDRS >= 8 spent longer time in bed,
      had later sleep offset times and had lower circadian rhythmicity than those with
      a HDRS<8 (p <= .036). Younger age and higher HDRS score correlated with later
      sleep onset and offset times, longer time in bed, higher WASO, lower sleep
      efficiency and later acrophase (p <= .023). Age was a significant predictor of
      delayed sleep and activity schedules (p <= .001). The profile of sleep-wake cycle
      disturbances associated with mood disorders changes with age, with prominent
      sleep phase delay during youth and reduced circadian strength in older persons.
      Conversely, disruptions in sleep consolidation seem more stable across age.

PMID- 24586293
TI  - Discrepancy between exercise performance, body composition, and sex steroid
      response after a six-week detraining period in professional soccer players.
AB  - PURPOSE: The aim of this study was to examine the effects of a six-week off
      season detraining period on exercise performance, body composition, and on
      circulating sex steroid levels in soccer players. METHODS: Fifty-five
      professional male soccer players, members of two Greek Superleague Teams (Team A,
      n = 23; Team B, n = 22), participated in the study. The first two weeks of the
      detraining period the players abstained from any physical activity. The following
      four weeks, players performed low-intensity (50%-60% of VO2max) aerobic running
      of 20 to 30 minutes duration three times per week. Exercise performance testing,
      anthropometry, and blood sampling were performed before and after the six-week
      experimental period. RESULTS: Our data showed that in both teams A and B the six
      week detraining period resulted in significant reductions in maximal oxygen
      consumption (60,31+/-2,52 vs 57,67+/-2,54; p<0.001, and 60,47+/-4,13 vs 58,30+/
      3,88; p<0.001 respectively), squat-jump (39,70+/-3,32 vs 37,30+/-3,08; p<0.001,
      and 41,05+/-3,34 vs 38,18+/-3,03; p<0.001 respectively), and countermovement-jump
      (41,04+/-3,99 vs 39,13+/-3,26; p<0.001 and 42,82+/-3,60 vs 40,09+/-2,79; p<0.001
      respectively), and significant increases in 10-meters sprint (1,74+/-0,063 vs
      1,79+/-0,064; p<0.001, and 1,73+/-0,065 vs 1,78+/-0,072; p<0.001 respectively),
      20-meters sprint (3,02+/-0,05 vs 3,06+/-0,06; p<0.001, and 3,01+/-0,066 vs 3,06+/
      0,063; p<0.001 respectively), body fat percentage (Team A; p<0.001, Team B;
      p<0.001), and body weight (Team A; p<0.001, Team B; p<0.001). Neither team
      displayed any significant changes in the resting concentrations of total
      testosterone, free-testosterone, dehydroepiandrosterone-sulfate, Delta4
      androstenedione, estradiol, luteinizing hormone, follicle-stimulating hormone,
      and prolactin. Furthermore, sex steroids levels did not correlate with exercise
      performance parameters. CONCLUSION: Our results suggest that the six-week
      detraining period resulted in a rapid loss of exercise performance adaptations
      and optimal body composition status, but did not affect sex steroid resting
      levels. The insignificant changes in sex steroid concentration indicate that
      these hormones were a non-contributing parameter for the observed negative
      effects of detraining on exercise performance and body composition.

PMID- 24586294
TI  - Sense transgene-induced post-transcriptional gene silencing in tobacco
      compromises the splicing of endogenous counterpart genes.
AB  - Sense transgene-induced post-transcriptional gene silencing (S-PTGS) is thought
      to be a type of RNA silencing in which ARGONAUTE1 directs the small interfering
      RNA (siRNA)-mediated cleavage of a target mRNA in the cytoplasm. Here, we report
      that the altered splicing of endogenous counterpart genes is a main cause for the
      reduction of their mature mRNA levels. After the S-PTGS of a tobacco endoplasmic
      reticulum omega-3 fatty acid desaturase (NtFAD3) gene, 3'-truncated,
      polyadenylated endo-NtFAD3 transcripts and 5'-truncated, intron-containing endo
      NtFAD3 transcripts were detected in the total RNA fraction. Although
      transcription proceeded until the last exon of the endogenous NtFAD3 gene, intron
      containing NtFAD3 transcripts accumulated in the nucleus of the S-PTGS plants.
      Several intron-containing NtFAD3 transcripts harboring most of the exon sequences
      were generated when an endogenous silencing suppressor gene, rgs-CaM, was
      overexpressed in the S-PTGS plants. These intron-containing NtFAD3 splice
      variants were generated in the presence of NtFAD3 siRNAs that are homologous to
      the nucleotide sequences of these splice variants. The results of this study
      indicate that the inhibition of endo-NtFAD3 gene expression is primarily directed
      via the alteration of splicing and not by cytoplasmic slicer activity. Our
      results suggest that the transgene and intron-containing endogenous counterpart
      genes are differentially suppressed in S-PTGS plants. 

PMID- 24586295
TI  - Mode of delivery and offspring body mass index, overweight and obesity in adult
      life: a systematic review and meta-analysis.
AB  - BACKGROUND: It has been suggested that mode of delivery, a potentially powerful
      influence upon long-term health, may affect later life body mass index (BMI). We
      conducted a systematic review and meta-analysis of the effect of Caesarean
      section (CS) and vaginal delivery (VD) on offspring BMI, overweight (BMI>25) and
      obesity (BMI>30) in adulthood. Secondary outcomes were subgroup analyses by
      gender and type of CS (in-labour/emergency, pre-labour/elective). METHODS: Using
      a predefined search strategy, Pubmed, Google Scholar and Web of Science were
      searched for any article published before 31(st) March 2012, along with
      references of any studies deemed relevant. Studies were selected if they reported
      birth characteristics and long-term offspring follow-up into adulthood. Aggregate
      data from relevant studies were extracted onto a pre-piloted data table. A random
      effects meta-analysis was carried out in RevMan5. Results are illustrated using
      forest plots and funnel plots, and presented as mean differences or odds ratios
      (OR) and 95% confidence intervals. RESULTS: Thirty-five studies were identified
      through the search, and 15 studies with a combined population of 163,796
      [corrected] were suitable for inclusion in the meta-analysis. Comparing all CS to
      VD in pooled-gender unadjusted analyses, mean BMI difference was 0.44 kg.m(-2)
      (0.17, 0.72; p = 0.002), OR for incidence of overweight was 1.26 (1.16, 1.38;
      p<0.00001) and OR for incidence of obesity was 1.22 (1.05, 1.42; p = 0.01).
      Heterogeneity was low in all primary analyses. Similar results were found in
      gender-specific subgroup analyses. Subgroup analyses comparing type of CS to VD
      showed no significant impact on any outcome. CONCLUSIONS: There is a strong
      association between CS and increased offspring BMI, overweight and obesity in
      adulthood. Given the rising CS rate worldwide there is a need to determine
      whether this is causal, or reflective of confounding influences. SYSTEMATIC
      REVIEW REGISTRATION: An a priori protocol was registered on PROSPERO
      (registration number: CRD42011001851).

PMID- 24586296
TI  - Population connectivity and phylogeography of a coastal fish, Atractoscion
      aequidens (Sciaenidae), across the Benguela Current region: evidence of an
      ancient vicariant event.
AB  - Contemporary patterns of genetic diversity and population connectivity within
      species can be influenced by both historical and contemporary barriers to gene
      flow. In the marine environment, present day oceanographic features such as
      currents, fronts and upwelling systems can influence dispersal of eggs/larvae
      and/juveniles/adults, shaping population substructuring. The Benguela Current
      system in the southeastern Atlantic is one of the oldest upwelling systems in the
      world, and provides a unique opportunity to investigate the relative influence of
      contemporary and historical mechanisms shaping the evolutionary history of warm
      temperate fish species. Using the genetic variation in the mitochondrial DNA
      Control Region and eight nuclear microsatellite DNA loci, we identified the
      presence of two highly divergent populations in a vagile and warm-temperate fish
      species, Atractoscion aequidens, across the Benguela region. The geographical
      distributions of the two populations, on either side of the perennial upwelling
      cell, suggest a strong correlation between the oceanographic features of the
      system and the breakdown of gene flow within this species. Genetic divergence
      (mtDNA phi ST = 0.902, microsatellite F ST = 0.055: probability of genetic
      homogeneity for either marker = p<0.001), absence of migrants (less than 1% per
      generation) between populations and coalescent estimates of time since most
      recent common ancestor suggest that the establishment of the main oceanographic
      features of the system (2 million years ago), particularly the strengthening and
      position of the perennial upwelling cell, is the most likely mechanism behind the
      observed isolation. Concordance between mitochondrial and nuclear genetic markers
      indicates that isolation and divergence of the northern and southern Benguela
      populations of A. aequidens occurred deep in the past and has continued to the
      present day. These findings suggest that the Benguela Current system may
      constitute an ancient and impermeable barrier to gene flow for warm-temperate
      fish species.

PMID- 24586297
TI  - A structural framework for a near-minimal form of life: mass and compositional
      analysis of the helical mollicute Spiroplasma melliferum BC3.
AB  - Spiroplasma melliferum is a wall-less bacterium with dynamic helical geometry.
      This organism is geometrically well defined and internally well ordered, and has
      an exceedingly small genome. Individual cells are chemotactic, polar, and swim
      actively. Their dynamic helicity can be traced at the molecular level to a highly
      ordered linear motor (composed essentially of the proteins fib and MreB) that is
      positioned on a defined helical line along the internal face of the cell's
      membrane. Using an array of complementary, informationally overlapping
      approaches, we have taken advantage of this uniquely simple, near-minimal life
      form and its helical geometry to analyze the copy numbers of Spiroplasma's
      essential parts, as well as to elucidate how these components are spatially
      organized to subserve the whole living cell. Scanning transmission electron
      microscopy (STEM) was used to measure the mass-per-length and mass-per-area of
      whole cells, membrane fractions, intact cytoskeletons and cytoskeletal
      components. These local data were fit into whole-cell geometric parameters
      determined by a variety of light microscopy modalities. Hydrodynamic data
      obtained by analytical ultracentrifugation allowed computation of the hydration
      state of whole living cells, for which the relative amounts of protein, lipid,
      carbohydrate, DNA, and RNA were also estimated analytically. Finally, ribosome
      and RNA content, genome size and gene expression were also estimated (using
      stereology, spectroscopy and 2D-gel analysis, respectively). Taken together, the
      results provide a general framework for a minimal inventory and arrangement of
      the major cellular components needed to support life. 

PMID- 24586299
TI  - Chromatic illumination discrimination ability reveals that human colour constancy
      is optimised for blue daylight illuminations.
AB  - The phenomenon of colour constancy in human visual perception keeps surface
      colours constant, despite changes in their reflected light due to changing
      illumination. Although colour constancy has evolved under a constrained subset of
      illuminations, it is unknown whether its underlying mechanisms, thought to
      involve multiple components from retina to cortex, are optimised for particular
      environmental variations. Here we demonstrate a new method for investigating
      colour constancy using illumination matching in real scenes which, unlike
      previous methods using surface matching and simulated scenes, allows testing of
      multiple, real illuminations. We use real scenes consisting of solid familiar or
      unfamiliar objects against uniform or variegated backgrounds and compare
      discrimination performance for typical illuminations from the daylight
      chromaticity locus (approximately blue-yellow) and atypical spectra from an
      orthogonal locus (approximately red-green, at correlated colour temperature 6700
      K), all produced in real time by a 10-channel LED illuminator. We find that
      discrimination of illumination changes is poorer along the daylight locus than
      the atypical locus, and is poorest particularly for bluer illumination changes,
      demonstrating conversely that surface colour constancy is best for blue daylight
      illuminations. Illumination discrimination is also enhanced, and therefore colour
      constancy diminished, for uniform backgrounds, irrespective of the object type.
      These results are not explained by statistical properties of the scene signal
      changes at the retinal level. We conclude that high-level mechanisms of colour
      constancy are biased for the blue daylight illuminations and variegated
      backgrounds to which the human visual system has typically been exposed. 

PMID- 24586298
TI  - Generation of recombinant antibodies to rat GABAA receptor subunits by affinity
      selection on synthetic peptides.
AB  - The abundance and physiological importance of GABAA receptors in the central
      nervous system make this neurotransmitter receptor an attractive target for
      localizing diagnostic and therapeutic biomolecules. GABAA receptors are expressed
      within the retina and mediate synaptic signaling at multiple stages of the visual
      process. To generate monoclonal affinity reagents that can specifically recognize
      GABAA receptor subunits, we screened two bacteriophage M13 libraries, which
      displayed human scFvs, by affinity selection with synthetic peptides predicted to
      correspond to extracellular regions of the rat alpha1 and beta2 GABAA subunits.
      We isolated three anti-beta2 and one anti-alpha1 subunit specific scFvs.
      Fluorescence polarization measurements revealed all four scFvs to have low
      micromolar affinities with their cognate peptide targets. The scFvs were capable
      of detecting fully folded GABAA receptors heterologously expressed by Xenopus
      laevis oocytes, while preserving ligand-gated channel activity. Moreover, A10,
      the anti-alpha1 subunit-specific scFv, was capable of detecting native GABAA
      receptors in the mouse retina, as observed by immunofluorescence staining. In
      order to improve their apparent affinity via avidity, we dimerized the A10 scFv
      by fusing it to the Fc portion of the IgG. The resulting scFv-Fc construct had a
      Kd of ~26 nM, which corresponds to an approximately 135-fold improvement in
      binding, and a lower detection limit in dot blots, compared to the monomeric
      scFv. These results strongly support the use of peptides as targets for
      generating affinity reagents to membrane proteins and encourage investigation of
      molecular conjugates that use scFvs as anchoring components to localize reagents
      of interest at GABAA receptors of retina and other neural tissues, for studies of
      receptor activation and subunit structure. 

PMID- 24586300
TI  - Eucommia ulmoides cortex, geniposide and aucubin regulate lipotoxicity through
      the inhibition of lysosomal BAX.
AB  - In this study we examined the inhibition of hepatic dyslipidemia by Eucommia
      ulmoides extract (EUE). Using a screening assay for BAX inhibition we determined
      that EUE regulates BAX-induced cell death. Among various cell death stimuli
      tested EUE regulated palmitate-induced cell death, which involves lysosomal BAX
      translocation. EUE rescued palmitate-induced inhibition of lysosomal V-ATPase,
      alpha-galactosidase, alpha-mannosidase, and acid phosphatase, and this effect was
      reversed by bafilomycin, a lysosomal V-ATPase inhibitor. The active components of
      EUE, aucubin and geniposide, showed similar inhibition of palmitate-induced cell
      death to that of EUE through enhancement of lysosome activity. Consistent with
      these in vitro findings, EUE inhibited the dyslipidemic condition in a high-fat
      diet animal model by regulating the lysosomal localization of BAX. This study
      demonstrates that EUE regulates lipotoxicity through a novel mechanism of
      enhanced lysosomal activity leading to the regulation of lysosomal BAX activation
      and cell death. Our findings further indicate that geniposide and aucubin, active
      components of EUE, may be therapeutic candidates for non-alcoholic fatty liver
      disease. 

PMID- 24586301
TI  - No association of four candidate genetic variants in MnSOD and SYNIII with
      Parkinson's disease in two Chinese populations.
AB  - BACKGROUND: The manganese superoxide dismutase (MnSOD) gene, which encodes a
      chief reactive oxygen species (ROS) scavenging enzyme, has been reported to be
      associated with the risk of developing sporadic Parkinson's disease (PD) in some
      Asian races and the synapsin III (SYN3) gene with some neuropsychiatric diseases.
      OBJECTIVE: To explore the associations between the MnSOD and SYN III variations
      and PD in two Chinese populations from mainland China and Singapore. METHODS: We
      recruited 2342 subjects including 1200 sporadic PD patients and 1142 healthy
      controls from two independent Asian countries. Using a case-control methodology,
      we genotyped the single nucleotide polymorphisms (SNP) in MnSOD (rs4880) and SYN
      III (rs3788470, rs3827336, rs5998557) to explore the associations with risk of
      PD. RESULTS: The results showed the genotype distributions and minor allele
      frequencies (MAF) of MnSOD (rs4880) and SYN III (rs3788470, rs3827336, rs5998557)
      were not significantly different between PD patients and healthy controls in
      mainland China and Singapore, as well as in merged populations. CONCLUSIONS: The
      variations of MnSOD (rs4880) and SYN III (rs3788470, rs3827336, rs5998557) were
      not major risk factors for PD among Chinese, at least in our study populations.

PMID- 24586302
TI  - Perceptional and socio-demographic factors associated with household drinking
      water management strategies in rural Puerto Rico.
AB  - Identifying which factors influence household water management can help policy
      makers target interventions to improve drinking water quality for communities
      that may not receive adequate water quality at the tap. We assessed which
      perceptional and socio-demographic factors are associated with household drinking
      water management strategies in rural Puerto Rico. Specifically, we examined which
      factors were associated with household decisions to boil or filter tap water
      before drinking, or to obtain drinking water from multiple sources. We find that
      households differ in their management strategies depending on the institution
      that distributes water (i.e. government PRASA vs community-managed non-PRASA),
      perceptions of institutional efficacy, and perceptions of water quality.
      Specifically, households in PRASA communities are more likely to boil and filter
      their tap water due to perceptions of low water quality. Households in non-PRASA
      communities are more likely to procure water from multiple sources due to
      perceptions of institutional inefficacy. Based on informal discussions with
      community members, we suggest that water quality may be improved if PRASA systems
      improve the taste and odor of tap water, possibly by allowing for dechlorination
      prior to distribution, and if non-PRASA systems reduce the turbidity of water at
      the tap, possibly by increasing the degree of chlorination and filtering prior to
      distribution. Future studies should examine objective water quality standards to
      identify whether current management strategies are effective at improving water
      quality prior to consumption. 

PMID- 24586303
TI  - Comprehensive detection of genes causing a phenotype using phenotype sequencing
      and pathway analysis.
AB  - Discovering all the genetic causes of a phenotype is an important goal in
      functional genomics. We combine an experimental design for detecting independent
      genetic causes of a phenotype with a high-throughput sequencing analysis that
      maximizes sensitivity for comprehensively identifying them. Testing this approach
      on a set of 24 mutant strains generated for a metabolic phenotype with many known
      genetic causes, we show that this pathway-based phenotype sequencing analysis
      greatly improves sensitivity of detection compared with previous methods, and
      reveals a wide range of pathways that can cause this phenotype. We demonstrate
      our approach on a metabolic re-engineering phenotype, the PEP/OAA metabolic node
      in E. coli, which is crucial to a substantial number of metabolic pathways and
      under renewed interest for biofuel research. Out of 2157 mutations in these
      strains, pathway-phenoseq discriminated just five gene groups (12 genes) as
      statistically significant causes of the phenotype. Experimentally, these five
      gene groups, and the next two high-scoring pathway-phenoseq groups, either have a
      clear connection to the PEP metabolite level or offer an alternative path of
      producing oxaloacetate (OAA), and thus clearly explain the phenotype. These high
      scoring gene groups also show strong evidence of positive selection pressure,
      compared with strictly neutral selection in the rest of the genome. 

PMID- 24586304
TI  - The novel long noncoding RNA linc00467 promotes cell survival but is down
      regulated by N-Myc.
AB  - The worst subtype of neuroblastoma is caused by MYCN oncogene amplification and N
      Myc oncoprotein over-expression. Long noncoding RNAs (lncRNAs) are emerging as
      critical regulators of gene expression and tumourigenesis. While Myc oncoproteins
      are well-known to exert tumourigenic effects by regulating the expression of
      protein-coding genes and microRNAs, little is known about which lncRNAs are Myc
      targets and whether the Myc target lncRNAs play a role in Myc-induced
      oncogenesis. Here we performed differential gene expression studies using lncRNA
      microarray in neuroblastoma cells after transfection with control or N-Myc
      specific small interfering RNA (siRNA), and identified N-Myc target lncRNAs
      including the novel lncRNA linc00467, the expression and function of which were
      completely unknown. RT-PCR, chromatin immunoprecipitation and luciferase assays
      showed that N-Myc suppressed linc00467 gene expression through direct binding to
      the linc00467 gene promoter and reducing linc00467 promoter activity. While N-Myc
      suppressed the expression of RD3, the protein-coding gene immediately down-stream
      of linc00467 gene, through direct binding to the RD3 gene promoter and reducing
      RD3 promoter activity, linc00467 reduced RD3 mRNA expression. Moreover,
      Affymetrix microarray analysis revealed that one of genes significantly up
      regulated by linc00467 siRNA was the tumour suppressor gene DKK1. Importantly,
      knocking-down linc00467 expression with siRNA in neuroblastoma cells reduced the
      number of viable cells and increased the percentage of apoptotic cells, and co
      transfection with DKK1 siRNA blocked the effects. These findings therefore
      demonstrate that N-Myc-mediated suppression of linc00467 gene transcription
      counterintuitively blocks N-Myc-mediated reduction in RD3 mRNA expression, and
      reduces neuroblastoma cell survival by inducing DKK1 expression. 

PMID- 24586306
TI  - Variation in stem anatomical characteristics of Campanuloideae species in
      relation to evolutionary history and ecological preferences.
AB  - BACKGROUND: The detailed knowledge of plant anatomical characters and their
      variation among closely related taxa is key to understanding their evolution and
      function. We examined anatomical variation in 46 herbaceous taxa from the
      subfamily Campanuloideae (Campanulaceae) to link this information with their
      phylogeny, ecology and comparative material of 56 woody tropical taxa from the
      subfamily Lobelioideae. The species studied covered major environmental gradients
      from Mediterranean to Arctic zones, allowing us to test hypotheses on the
      evolution of anatomical structure in relation to plant competitive ability and
      ecological preferences. METHODOLOGY/PRINCIPAL FINDINGS: To understand the
      evolution of anatomical diversity, we reconstructed the phylogeny of studied
      species from nucleotide sequences and examined the distribution of anatomical
      characters on the resulting phylogenetic tree. Redundancy analysis, with
      phylogenetic corrections, was used to separate the evolutionary inertia from the
      adaptation to the environment. A large anatomical diversity exists within the
      Campanuloideae. Traits connected with the quality of fibres were the most
      congruent with phylogeny, and the Rapunculus 2 ("phyteumoid") clade was
      especially distinguished by a number of characters (absence of fibres, pervasive
      parenchyma, type of rays) from two other clades (Campanula s. str. and Rapunculus
      1) characterized by the dominance of fibres and the absence of parenchyma.
      Septate fibres are an exclusive trait in the Lobelioideae, separating it clearly
      from the Campanuloideae where annual rings, pervasive parenchyma and crystals in
      the phellem are characteristic features. CONCLUSIONS/SIGNIFICANCE: Despite clear
      phylogenetic inertia in the anatomical features studied, the ecological
      attributes and plant height had a significant effect on anatomical divergence.
      From all three evolutionary clades, the taller species converged towards similar
      anatomical structure, characterized by a smaller number of early wood vessels of
      large diameter, thinner cell-walls and alternate intervessel pits, while the
      opposite trend was found in small Arctic and alpine taxa. This supports the
      existing generalization that narrower vessels allow plants to grow in colder
      places where they can avoid freezing-induced embolism, while taller plants have
      wider vessels to minimize hydraulic resistance with their greater path lengths.

PMID- 24586305
TI  - Alarming signs and symptoms in febrile children in primary care: an observational
      cohort study in The Netherlands.
AB  - CONTEXT: Febrile children in primary care have a low risk for serious infection.
      Although several alarming signs and symptoms are proposed to have predictive
      value for serious infections, most are based on research in secondary care. The
      frequency of alarming signs/symptoms has not been established in primary care;
      however, in this setting differences in occurrence may influence their predictive
      value for serious infections. OBJECTIVE: To determine the frequency of alarming
      signs/symptoms in febrile children in primary care. DESIGN: Observational cohort
      study. Clinical information was registered in a semi-structured way and manually
      recoded. SETTING: General practitioners' out-of-hours service. SUBJECTS: Face-to
      face patient contacts concerning children (aged <=16 years) with fever were
      eligible for inclusion. MAIN OUTCOME MEASURES: Frequency of 18 alarming signs and
      symptoms as reported in the literature. RESULTS: A total of 10,476 patient
      contacts were included. The frequency of alarming signs/symptoms ranged from n =
      1 (ABC instability; <0.1%) to n = 2,207 (vomiting & diarrhea; 21.1%). Of all
      children, 59.7% had one or more alarming signs and/or symptoms. Several alarming
      signs/symptoms were poorly registered with the frequency of missing information
      ranging from 1,347 contacts (temperature >40 degrees C as reported by the
      parents; 12.9%) to 8,647 contacts (parental concern; 82.5%). CONCLUSION: Although
      the prevalence of specific alarming signs/symptoms is low in primary care, >=50%
      of children have one or more alarming signs/symptoms. There is a need to
      determine the predictive value of alarming signs/symptoms not only for serious
      infections in primary care, but as well for increased risk of a complicated
      course of the illness.

PMID- 24586308
TI  - Temsirolimus inhibits proliferation and migration in retinal pigment epithelial
      and endothelial cells via mTOR inhibition and decreases VEGF and PDGF expression.
AB  - Due to their high prevalence, retinal vascular diseases including age related
      macular degeneration (AMD), retinal vein occlusions (RVO), diabetic retinopathy
      (DR) and diabetic macular edema have been major therapeutic targets over the last
      years. The pathogenesis of these diseases is complex and yet not fully
      understood. However, increased proliferation, migration and angiogenesis are
      characteristic cellular features in almost every retinal vascular disease. The
      introduction of vascular endothelial growth factor (VEGF) binding intravitreal
      treatment strategies has led to great advances in the therapy of these diseases.
      While the predominant part of affected patients benefits from the specific
      binding of VEGF by administering an anti-VEGF antibody into the vitreous cavity,
      a small number of non-responders exist and alternative or additional therapeutic
      strategies should therefore be evaluated. The mammalian target of rapamycin
      (mTOR) is a central signaling pathway that eventually triggers up-regulation of
      cellular proliferation, migration and survival and has been identified to play a
      key role in angiogenesis. In the present study we were able to show that both
      retinal pigment epithelial (RPE) cells as wells as human umbilical vein
      endothelial cells (HUVEC) are inhibited in proliferating and migrating after
      treatment with temsirolimus in non-toxic concentrations. Previous studies suggest
      that the production of VEGF, platelet derived growth factor (PDGF) and other
      important cytokines is not only triggered by hypoxia but also by mTOR itself. Our
      results indicate that temsirolimus decreases VEGF and PDGF expression on RNA and
      protein levels significantly. We therefore believe that the mTOR inhibitor
      temsirolimus might be a promising drug in the future and it seems worthwhile to
      evaluate complementary therapeutic effects with anti-VEGF drugs for patients not
      profiting from mono anti-VEGF therapy alone. 

PMID- 24586307
TI  - T cells and macrophages responding to oxidative damage cooperate in pathogenesis
      of a mouse model of age-related macular degeneration.
AB  - Age-related macular degeneration (AMD) is a major disease affecting central
      vision, but the pathogenic mechanisms are not fully understood. Using a mouse
      model, we examined the relationship of two factors implicated in AMD development:
      oxidative stress and the immune system. Carboxyethylpyrrole (CEP) is a lipid
      peroxidation product associated with AMD in humans and AMD-like pathology in
      mice. Previously, we demonstrated that CEP immunization leads to retinal
      infiltration of pro-inflammatory M1 macrophages before overt retinal
      degeneration. Here, we provide direct and indirect mechanisms for the effect of
      CEP on macrophages, and show for the first time that antigen-specific T cells
      play a leading role in AMD pathogenesis. In vitro, CEP directly induced M1
      macrophage polarization and production of M1-related factors by retinal pigment
      epithelial (RPE) cells. In vivo, CEP eye injections in mice induced acute pro
      inflammatory gene expression in the retina and human AMD eyes showed
      distinctively diffuse CEP immunolabeling within RPE cells. Importantly,
      interferon-gamma (IFN-gamma) and interleukin-17 (IL-17)-producing CEP-specific T
      cells were identified ex vivo after CEP immunization and promoted M1 polarization
      in co-culture experiments. Finally, T cell immunosuppressive therapy inhibited
      CEP-mediated pathology. These data indicate that T cells and M1 macrophages
      activated by oxidative damage cooperate in AMD pathogenesis. 

PMID- 24586310
TI  - The association between self-reported stigma and loss-to-follow up in treatment
      eligible HIV positive adults in rural Kwazulu-Natal, South Africa.
AB  - BACKGROUND: The relationship between loss-to-follow-up (LTFU) in HIV treatment
      and care programmes and psychosocial factors, including self-reported stigma, is
      important to understand. This prospective cohort study explored stigma and LTFU
      in treatment eligible adults who had yet not started antiretroviral therapy
      (ART). METHODS: Psychosocial, clinical and demographic data were collected at a
      baseline interview. Self-reported stigma was measured with a multi-item scale.
      LTFU was defined as not attending clinic in the 90 days since last appointment or
      before death. Data was collected between January 2009 and January 2013 and
      analysed using Cox Regression. RESULTS: 380 individuals were recruited (median
      time in study 3.35 years, total time at risk 1065.81 person-years). 203 were
      retained (53.4%), 109 were LTFU (28.7%), 48 had died and were not LTFU at death
      (12.6%) and 20 had transferred out (5.3%). The LTFU rate was 10.65 per 100 person
      years (95% CI: 8.48-12.34). 362 individuals (95.3%) started ART. Stigma total
      score (categorised in quartiles) was not significantly associated with LTFU in
      either univariable or multivariable analysis (adjusting for other variables in
      the final model): second quartile aHR 0.77 (95%CI: 0.41-1.46), third quartile aHR
      1.20(95%CI: 0.721-2.04), fourth quartile aHR 0.62 (95%CI: 0.35-1.11). In the
      final multivariable model, higher LTFU rates were associated with male gender,
      increased openness with friends/family and believing that community problems
      would be solved at higher levels. Lower LTFU rates were independently associated
      with increased year of age, greater reliance on family/friends, and having
      children. CONCLUSIONS: Demographic and other psychosocial factors were more
      closely related to LTFU than self-reported stigma. This may be consistent with
      high levels of social exposure to HIV and ART and with stigma affecting LTFU less
      than other stages of care. Research and clinical implications are discussed.

PMID- 24586311
TI  - Extended adjuvant tamoxifen for early breast cancer: a meta-analysis.
AB  - BACKGROUND: Hormone receptor positive breast cancer is characterized by the
      potential for disease recurrence many years after initial diagnosis. Endocrine
      therapy has been shown to reduce the risk of such recurrence, but the optimal
      duration of endocrine therapy remains unclear. METHODS: We conducted a systematic
      review and meta-analysis to quantify the benefits and harms of extended adjuvant
      tamoxifen (>5 years of therapy) compared with adjuvant tamoxifen (5 years of
      therapy). Odds ratios (ORs) and 95% confidence intervals (CIs) were computed for
      disease recurrence, death and adverse events. Subgroup analyses by timing of
      recurrence and baseline lymph node and menopause status were carried. RESULTS:
      Five trials comprising 21,554 patients were included. Extended adjuvant tamoxifen
      was not associated with a significant reduction in the risk of recurrence
      (OR:0.89, 95% CI 0.76-1.05, p = 0.17). There was no association between extended
      adjuvant tamoxifen and all-cause death (OR:0.99, 95% CI 0.84-1.16, p = 0.88).
      There was an apparent reduction in risk of recurrence occurring after completion
      of extended adjuvant tamoxifen with little evidence of effect during therapy,
      however, this difference was not significant (p for difference 0.10). Subgroup
      analysis suggested that a greater effect size among lymph node positive patients
      compared with those who are lymph node negative (NNT: 25 vs. 49). There was no
      apparent difference in the effect between pre- and post-menopausal patients.
      Endometrial carcinoma was substantially more frequent with extended adjuvant
      tamoxifen (OR:2.06, 95% CI 1.65-2.58, p<0.001, number needed to harm:89).
      CONCLUSION: In unselected patients, extended adjuvant tamoxifen is not associated
      with a significant reduction in recurrence, or a reduction in all-cause death.
      Patients with lymph node positive breast cancer may derive some benefit.
      Reduction in the risk of recurrence appears to occur only after completion of
      extended adjuvant therapy.

PMID- 24586309
TI  - On the variability of the Dmanisi mandibles.
AB  - The description of a new skull (D4500) from the Dmanisi site (Republic of
      Georgia) has reopened the debate about the morphological variability within the
      genus Homo. The new skull fits with a mandible (D2600) often referred as 'big' or
      'enigmatic' because of its differences with the other Dmanisi mandibles (D211 and
      D2735). In this report we present a comparative study of the variability of the
      Dmanisi mandibles under a different perspective, as we focus in morphological
      aspects related to growth and development. We have followed the notion of
      modularity and phenotypic integration in order to understand the architectural
      differences observed within the sample. Our study reveals remarkable shape
      differences between D2600 and the other two mandibles, that are established early
      in the ontogeny (during childhood or even before) and that do not depend on size
      or sexual dimorphism. In addition, D2600 exhibits a mosaic of primitive and
      derived features regarding the Homo clade, which is absent in D211 and D2735.
      This mosaic expression is related to the location of the features and can be
      explained under the concept of modularity. Our study would support the
      possibility of two different paleodemes represented at the Dmanisi site. This
      hypothesis has been previously rejected on the basis that all the individuals
      were constrained in the same stratigraphic and taphonomic settings. However, our
      revision of the complex Dmanisi stratigraphy suggests that the accumulation could
      cover an undetermined period of time. Even if "short" in geological terms, the
      hominin accumulation was not necessarily synchronic. In the same line we discard
      that the differences between D2600 and the small mandibles are consequence of
      wear-related dentoalveolar remodeling. In addition, dental wear pattern of D2600
      could suggest an adaptation to a different ecological niche than the other
      Dmanisi individuals.

PMID- 24586313
TI  - Rapid and accurate evaluation of the quality of commercial organic fertilizers
      using near infrared spectroscopy.
AB  - The composting industry has been growing rapidly in China because of a boom in
      the animal industry. Therefore, a rapid and accurate assessment of the quality of
      commercial organic fertilizers is of the utmost importance. In this study, a
      novel technique that combines near infrared (NIR) spectroscopy with partial least
      squares (PLS) analysis is developed for rapidly and accurately assessing
      commercial organic fertilizers quality. A total of 104 commercial organic
      fertilizers were collected from full-scale compost factories in Jiangsu Province,
      east China. In general, the NIR-PLS technique showed accurate predictions of the
      total organic matter, water soluble organic nitrogen, pH, and germination index;
      less accurate results of the moisture, total nitrogen, and electrical
      conductivity; and the least accurate results for water soluble organic carbon.
      Our results suggested the combined NIR-PLS technique could be applied as a
      valuable tool to rapidly and accurately assess the quality of commercial organic
      fertilizers. 

PMID- 24586312
TI  - Quantitative trait loci affecting atherosclerosis at the aortic root identified
      in an intercross between DBA2J and 129S6 apolipoprotein E-null mice.
AB  - Apolipoprotein E-null mice on a DBA/2J genetic background (DBA-apoE) are highly
      susceptible to atherosclerosis in the aortic root area compared with those on a
      129S6 background (129-apoE). To explore atherosclerosis-responsible genetic
      regions, we performed a quantitative trait locus (QTL) analysis using 172 male
      and 137 female F2 derived from an intercross between DBA-apoE and 129-apoE mice.
      A genome-wide scan identified two significant QTL for the size of lesions at the
      root: one is Ath44 on Chromosome (Chr) 1 at 158 Mb, and the other Ath45 on Chr 2
      at 162 Mb. Ath44 co-localizes with but appears to be independent of a previously
      reported QTL, Ath1, while Ath45 is a novel QTL. DBA alleles of both Ath44 and
      Ath45 confer atherosclerosis-susceptibility. In addition, a QTL on Chr 14 at 73
      Mb was found significant only in males, and 129 allele conferring susceptibility.
      Further analysis detected female-specific interactions between a second QTL on
      Chr 1 at 73 Mb and a QTL on Chr 3 at 21 Mb, and between Chr 7 at 84 Mb and Chr 12
      at 77 Mb. These loci for the root atherosclerosis were independent of QTLs for
      plasma total cholesterol and QTLs for triglycerides, but a QTL for HDL (Chr 1 at
      126 Mb) overlapped with the Ath44. Notably, haplotype analysis among 129S6,
      DBA/2J and C57BL/6 genomes and their gene expression data narrowed the candidate
      regions for Ath44 and Ath45 to less than 5 Mb intervals where multiple genome
      wide associations with cardiovascular phenotypes have also been reported in
      humans. SNPs in or near Fmo3, Sele and Selp for Ath44, and Lbp and Pkig for Ath45
      were suggested for further investigation as potential candidates underlying the
      atherosclerosis susceptibility.

PMID- 24586314
TI  - Human umbilical cord mesenchymal stem cells transplantation promotes cutaneous
      wound healing of severe burned rats.
AB  - BACKGROUND: Severe burns are a common and highly lethal trauma. The key step for
      severe burn therapy is to promote the wound healing as early as possible, and
      reports indicate that mesenchymal stem cell (MSC) therapy contributes to
      facilitate wound healing. In this study, we investigated effect of human
      umbilical cord MSCs (hUC-MSCs) could on wound healing in a rat model of severe
      burn and its potential mechanism. METHODS: Adult male Wistar rats were randomly
      divided into sham, burn, and burn transplanted hUC-MSCs. GFP labeled hUC-MSCs or
      PBS was intravenous injected into respective groups. The rate of wound closure
      was evaluated by Image Pro Plus. GFP-labeled hUC-MSCs were tracked by in vivo
      bioluminescence imaging (BLI), and human-specific DNA expression in wounds was
      detected by PCR. Inflammatory cells, neutrophils, macrophages, capillaries and
      collagen types I/III in wounds were evaluated by histochemical staining. Wound
      blood flow was evaluated by laser Doppler blood flow meter. The levels of
      proinflammatory and anti-inflammatory factors, VEGF, collagen types I/III in
      wounds were analyzed using an ELISA. RESULTS: We found that wound healing was
      significantly accelerated in the hUC-MSC therapy group. The hUC-MSCs migrated
      into wound and remarkably decreased the quantity of infiltrated inflammatory
      cells and levels of IL-1, IL-6, TNF-alpha and increased levels of IL-10 and TSG-6
      in wounds. Additionally, the neovascularization and levels of VEGF in wounds in
      the hUC-MSC therapy group were markedly higher than those in other control
      groups. The ratio of collagen types I and III in the hUC-MSC therapy group were
      markedly higher than that in the burn group at indicated time after
      transplantation. CONCLUSION: The study suggests that hUC-MSCs transplantation can
      effectively improve wound healing in severe burned rat model. Moreover, these
      data might provide the theoretical foundation for the further clinical
      application of hUC-MSC in burn areas.

PMID- 24586315
TI  - The fire-walker's high: affect and physiological responses in an extreme
      collective ritual.
AB  - How do people feel during extreme collective rituals? Despite longstanding
      speculation, few studies have attempted to quantify ritual experiences. Using a
      novel pre/post design, we quantified physiological fluctuations (heart rates) and
      self-reported affective states from a collective fire-walking ritual in a
      Mauritian Hindu community. Specifically, we compared changes in levels of
      happiness, fatigue, and heart rate reactivity among high-ordeal participants
      (fire-walkers), low-ordeal participants (non-fire-walking participants with
      familial bonds to fire-walkers) and spectators (unrelated/unknown to the fire
      walkers). We observed that fire-walkers experienced the highest increase in heart
      rate and reported greater happiness post-ritual compared to low-ordeal
      participants and spectators. Low-ordeal participants reported increased fatigue
      after the ritual compared to both fire-walkers and spectators, suggesting
      empathetic identification effects. Thus, witnessing the ritualistic suffering of
      loved ones may be more exhausting than experiencing suffering oneself. The
      findings demonstrate that the level of ritual involvement is important for
      shaping affective responses to collective rituals. Enduring a ritual ordeal is
      associated with greater happiness, whereas observing a loved-one endure a ritual
      ordeal is associated with greater fatigue post-ritual. 

PMID- 24586316
TI  - Reading direction and the central perceptual span in Urdu and English.
AB  - BACKGROUND: Normal reading relies on the reader making a series of saccadic eye
      movements along lines of text, separated by brief fixational pauses during which
      visual information is acquired from a region of text. In English and other
      alphabetic languages read from left to right, the region from which useful
      information is acquired during each fixational pause is generally reported to
      extend further to the right of each fixation than to the left. However, the
      asymmetry of the perceptual span for alphabetic languages read in the opposite
      direction (i.e., from right to left) has received much less attention.
      Accordingly, in order to more fully investigate the asymmetry in the perceptual
      span for these languages, the present research assessed the influence of reading
      direction on the perceptual span for bilingual readers of Urdu and English.
      METHODS AND FINDINGS: Text in Urdu and English was presented either entirely as
      normal or in a gaze-contingent moving-window paradigm in which a region of text
      was displayed as normal at the reader's point of fixation and text outside this
      region was obscured. The windows of normal text extended symmetrically 0.5
      degrees  of visual angle to the left and right of fixation, or asymmetrically by
      increasing the size of each window to 1.5 degrees  or 2.5 degrees  to either the
      left or right of fixation. When participants read English, performance for the
      window conditions was superior when windows extended to the right. However, when
      reading Urdu, performance was superior when windows extended to the left, and was
      essentially the reverse of that observed for English. CONCLUSION: These findings
      provide a novel indication that the perceptual span is modified by the language
      being read to produce an asymmetry in the direction of reading and show for the
      first time that such an asymmetry occurs for reading Urdu.

PMID- 24586317
TI  - Insights into the development and evolution of exaggerated traits using de novo
      transcriptomes of two species of horned scarab beetles.
AB  - Scarab beetles exhibit an astonishing variety of rigid exo-skeletal outgrowths,
      known as "horns". These traits are often sexually dimorphic and vary dramatically
      across species in size, shape, location, and allometry with body size. In many
      species, the horn exhibits disproportionate growth resulting in an exaggerated
      allometric relationship with body size, as compared to other traits, such as
      wings, that grow proportionately with body size. Depending on the species, the
      smallest males either do not produce a horn at all, or they produce a
      disproportionately small horn for their body size. While the diversity of horn
      shapes and their behavioural ecology have been reasonably well studied, we know
      far less about the proximate mechanisms that regulate horn growth. Thus, using
      454 pyrosequencing, we generated transcriptome profiles, during horn growth and
      development, in two different scarab beetle species: the Asian rhinoceros beetle,
      Trypoxylus dichotomus, and the dung beetle, Onthophagus nigriventris. We obtained
      over half a million reads for each species that were assembled into over 6,000
      and 16,000 contigs respectively. We combined these data with previously published
      studies to look for signatures of molecular evolution. We found a small subset of
      genes with horn-biased expression showing evidence for recent positive selection,
      as is expected with sexual selection on horn size. We also found evidence of
      relaxed selection present in genes that demonstrated biased expression between
      horned and horn-less morphs, consistent with the theory of developmental
      decoupling of phenotypically plastic traits. 

PMID- 24586318
TI  - A DTC niche plexus surrounds the germline stem cell pool in Caenorhabditis
      elegans.
AB  - The mesenchymal distal tip cell (DTC) provides the niche for Caenorhabditis
      elegans germline stem cells (GSCs). The DTC has a complex cellular architecture:
      its cell body caps the distal gonadal end and contacts germ cells extensively,
      but it also includes multiple cellular processes that extend along the germline
      tube and intercalate between germ cells. Here we use the lag-2 DTC promoter to
      drive expression of myristoylated GFP, which highlights DTC membranes and permits
      a more detailed view of DTC architecture. We find that short processes
      intercalating between germ cells contact more germ cells than seen previously. We
      define this region of extensive niche contact with germ cells as the DTC plexus.
      The extent of the DTC plexus corresponds well with the previously determined
      extent of the GSC pool. Moreover, expression of a differentiation marker
      increases as germ cells move out of the plexus. Maintenance of this DTC plexus
      depends on the presence of undifferentiated germ cells, suggesting that germ cell
      state can influence niche architecture. The roles of this DTC architecture remain
      an open question. One idea is that the DTC plexus delivers Notch signaling to the
      cluster of germ cells comprising the GSC pool; another idea is that the plexus
      anchors GSCs at the distal end. 

PMID- 24586319
TI  - Polyphasic analysis of a middle ages coprolite microbiota, Belgium.
AB  - Paleomicrobiological investigations of a 14(th)-century coprolite found inside a
      barrel in Namur, Belgium were done using microscopy, a culture-dependent approach
      and metagenomics. Results were confirmed by ad hoc PCR--sequencing.
      Investigations yielded evidence for flora from ancient environment preserved
      inside the coprolite, indicated by microscopic observation of amoebal cysts,
      plant fibers, seeds, pollens and mold remains. Seventeen different bacterial
      species were cultured from the coprolite, mixing organisms known to originate
      from the environment and organisms known to be gut inhabitants. Metagenomic
      analyses yielded 107,470 reads, of which known sequences (31.9%) comprised 98.98%
      bacterial, 0.52% eukaryotic, 0.44% archaeal and 0.06% viral assigned reads. Most
      abundant bacterial phyla were Proteobacteria, Gemmatimonadetes, Actinobacteria
      and Bacteroidetes. The 16 S rRNA gene dataset yielded 132,000 trimmed reads and
      673 Operational Taxonomic Units. Most abundant bacterial phyla observed in the 16
      S rRNA gene dataset belonged to Proteobacteria, Firmicutes, Actinobacteria and
      Chlamydia. The Namur coprolite yielded typical gut microbiota inhabitants,
      intestinal parasites Trichuris and Ascaris and systemic pathogens Bartonella and
      Bordetella. This study adds knowledge to gut microbiota in medieval times.

PMID- 24586320
TI  - A voltage dependent non-inactivating Na+ channel activated during apoptosis in
      Xenopus oocytes.
AB  - Ion channels in the plasma membrane are important for the apoptotic process.
      Different types of voltage-gated ion channels are up-regulated early in the
      apoptotic process and block of these channels prevents or delays apoptosis. In
      the present investigation we examined whether ion channels are up-regulated in
      oocytes from the frog Xenopus laevis during apoptosis. The two-electrode voltage
      clamp technique was used to record endogenous ion currents in the oocytes. During
      staurosporine-induced apoptosis a voltage-dependent Na(+) current increased three
      fold. This current was activated at voltages more positive than 0 mV (midpoint of
      the open-probability curve was +55 mV) and showed almost no sign of inactivation
      during a 1-s pulse. The current was resistant to the Na(+)-channel blockers
      tetrodotoxin (1 uM) and amiloride (10 uM), while the Ca(2+)-channel blocker
      verapamil (50 uM) in the bath solution completely blocked the current. The
      intracellular Na(+) concentration increased in staurosporine-treated oocytes, but
      could be prevented by replacing extracellular Na(+) with either K(+) or
      Choline(+). Prevention of this influx of Na(+) also prevented the STS-induced up
      regulation of the caspase-3 activity, suggesting that the intracellular Na(+)
      increase is required to induce apoptosis. Taken together, we have found that a
      voltage dependent Na(+) channel is up-regulated during apoptosis and that influx
      of Na(+) is a crucial step in the apoptotic process in Xenopus oocytes.

PMID- 24586321
TI  - Changes in intestinal glucocorticoid sensitivity in early life shape the risk of
      epithelial barrier defect in maternal-deprived rats.
AB  - Glucocorticoids (GC) contribute to human intestine ontogeny and accelerate gut
      barrier development in preparation to birth. Rat gut is immature at birth, and
      high intestinal GC sensitivity during the first two weeks of life resembles that
      of premature infants. This makes suckling rats a model to investigate postpartum
      impact of maternal separation (MS)-associated GC release in preterm babies, and
      whether GC sensitivity may shape MS effects in immature gut. A 4 hours-MS applied
      once at postnatal day (PND)10 enhanced plasma corticosterone in male and female
      pups, increased by two times the total in vivo intestinal permeability (IP) to
      oral FITC-Dextran 4 kDa (FD4) immediately after the end of MS, and induced
      bacterial translocation (BT) to liver and spleen. Ussing chamber experiments
      demonstrated a 2-fold increase of permeability to FD4 in the colon immediately
      after the end of MS, but not in the ileum. Colonic permeability was not only
      increased for FD4 but also to intact horseradish peroxidase 44 kDa in MS pups. In
      vivo, the glucocorticoid receptor (GR) antagonist RU486 or ML7 blockade of myosin
      light chain kinase controlling epithelial cytoskeleton contraction prevented MS
      induced IP increase to oral FD4 and BT. In addition, the GR agonist dexamethasone
      dose-dependently mimicked MS-increase of IP to oral FD4. In contrast, MS effects
      on IP to oral FD4 and BT were absent at PND20, a model for full-term infant,
      characterized by a marked drop of IP to FD4 in response to dexamethasone, and
      decreased GR expression in the colon only compared to PND10 pups. These results
      show that high intestinal GC responsiveness in a rat model of prematurity defines
      a vulnerable window for a post-delivery MS, evoking immediate disruption of
      epithelial integrity in the large intestine, and increasing susceptibility to
      macromolecule passage and bacteremia.

PMID- 24586322
TI  - Efficient translation of Dnmt1 requires cytoplasmic polyadenylation and Musashi
      binding elements.
AB  - Regulation of DNMT1 is critical for epigenetic control of many genes and for
      genome stability. Using phylogenetic analysis we characterized a block of 27
      nucleotides in the 3'UTR of Dnmt1 mRNA identical between humans and Xenopus and
      investigated the role of the individual elements contained within it. This region
      contains a cytoplasmic polyadenylation element (CPE) and a Musashi binding
      element (MBE), with CPE binding protein 1 (CPEB1) known to bind to the former in
      mouse oocytes. The presence of these elements usually indicates translational
      control by elongation and shortening of the poly(A) tail in the cytoplasm of the
      oocyte and in some somatic cell types. We demonstrate for the first time
      cytoplasmic polyadenylation of Dnmt1 during periods of oocyte growth in mouse and
      during oocyte activation in Xenopus. Furthermore we show by RNA
      immunoprecipitation that Musashi1 (MSI1) binds to the MBE and that this element
      is required for polyadenylation in oocytes. As well as a role in oocytes, site
      directed mutagenesis and reporter assays confirm that mutation of either the MBE
      or CPE reduce DNMT1 translation in somatic cells, but likely act in the same
      pathway: deletion of the whole conserved region has more severe effects on
      translation in both ES and differentiated cells. In adult cells lacking MSI1
      there is a greater dependency on the CPE, with depletion of CPEB1 or CPEB4 by
      RNAi resulting in substantially reduced levels of endogenous DNMT1 protein and
      concurrent upregulation of the well characterised CPEB target mRNA cyclin B1. Our
      findings demonstrate that CPE- and MBE-mediated translation regulate DNMT1
      expression, representing a novel mechanism of post-transcriptional control for
      this gene.

PMID- 24586324
TI  - Estimating colorectal cancer treatment costs: a pragmatic approach exemplified by
      health insurance data from Germany.
AB  - BACKGROUND: The cost of colorectal cancer (CRC) treatment is a crucial parameter
      to inform cost-effectiveness analyses on CRC screening but it is not readily
      available and therefore often lacking. We aimed to elaborate and exemplify a
      pragmatic approach to estimate CRC treatment cost based on health insurance data
      from Germany. METHODS: We included two groups of persons who were continuously
      health-insured between 2005-2010: A) Cases: Persons with a hospital discharge
      diagnosis of CRC (ICD C18-C20) between 2007-2010 and no such a diagnosis between
      2005-2006 (to focus on incident CRC cases); B) Controls: Persons without a
      diagnosis of CRC during the observation period, matched to CRC cases by age and
      sex (matching factor: 1?5). We considered in-patient, out-patient and drug costs
      and calculated incremental costs as the difference in means between cases and
      controls. We divided costs into three phases of care (initial, intermediate and
      end-of-life phase). RESULTS: The initial, the intermediate and the end-of-life
      phase included 12,792, 5,280, and 3,779 CRC cases, respectively, and 63,960,
      26,400, and 18,895 controls. The mean incremental costs--annualized for each
      phase--were ?26,000, ?2,300, and ?51,700, respectively. The costs of the initial
      phase of care were higher for rectal than for colon cancer. Annualized stage
      specific cost estimates ranged from ?15,000 to ?21,300 for early stages and from
      ?29,800 to ?35,000 for late stages. CONCLUSION: This pragmatic and feasible
      approach provided plausible estimates of CRC treatment costs in Germany; being
      transferable to other settings, it may thus facilitate to weigh up potential
      savings in treatment costs against the resources required for CRC control
      programs in various countries.

PMID- 24586326
TI  - Egocentric fairness perception: emotional reactions and individual differences in
      overt responses.
AB  - Extensive research documents the existence of egocentric biases in the perception
      and application of justice norms. The origin of these biases remains poorly
      understood. We investigated both inter- and intra-individual differences in
      egocentric justice biases. Participants played an ultimatum game presumably with
      different anonymous players (simulated by a computer) in which they contributed
      differentially to the joint production of the initial endowment. We examined how
      contributions (low vs. high) affect proposers' offers and responders' acceptance
      decisions, as well as their fairness judgments and their emotional reactions to
      different types of offers (equal, equitable, unfair, and hyperfair). An
      egocentric bias in proposers' offers (indicating more flexible preferences) was
      found only in individualists and not in prosocials, suggesting differences in the
      motivations (or cognitions) underlying their choice of justice norms. Responders
      also showed egocentric biases in their judgments of fairness and in their
      emotional reactions to equal and equitable offers, but not in their acceptance
      decisions. Such dissociation might suggest that some form of emotion regulation
      occurred. Responders may evaluate offers on valence dimensions (e.g., goal
      conduciveness/outcome favorability and norm compatibility/justice) that are
      multiply interacting and potentially conflicting. The individual's
      acceptance/rejection decision reflects the relative weight attributed to
      competing appraisals. For this overt behavioral decision, the (personal)
      appraisal of outcome favorability that drives (analytical) acceptance of goal
      conducive outcome seems to be stronger than the (social) appraisal of outcome
      fairness, which may trigger covert (emotional) rejection of offers that are
      incompatible with justice norms. Our data show that the emotional reaction
      patterns provide a more fine-grained readout of the overall evaluation of the
      proposer's action, the underlying emotional dynamics of which may, in real life,
      strongly determine future interactions with specific partners. Further research
      on the relationship between emotion and behavior in economic games is needed to
      explore potential dissociations and long-term effects. 

PMID- 24586325
TI  - Mitochondrial DNA phylogeography of the Norway rat.
AB  - Central Eastern Asia, foremost the area bordering northern China and Mongolia,
      has been thought to be the geographic region where Norway rats (Rattus
      norvegicus) have originated. However recent fossil analyses pointed to their
      origin in southern China. Moreover, whereas analyses of fossils dated the
      species' origin as ~ 1.2-1.6 million years ago (Mya), molecular analyses yielded
      ~ 0.5-2.9 Mya. Here, to study the geographic origin of the Norway rat and its
      spread across the globe we analyzed new and all published mitochondrial DNA
      cytochrome-b (cyt-b; N = 156) and D-loop (N = 212) sequences representing wild
      rats from four continents and select inbred strains. Our results are consistent
      with an origin of the Norway rat in southern China ~ 1.3 Mya, subsequent
      prehistoric differentiation and spread in China and Asia from an initially weakly
      structured ancestral population, followed by further spread and differentiation
      across the globe during historic times. The recent spreading occurred mostly from
      derived European populations rather than from archaic Asian populations. We trace
      laboratory strains to wild lineages from Europe and North America and these
      represent a subset of the diversity of the rat; leaving Asian lineages largely
      untapped as a resource for biomedical models. By studying rats from Europe we
      made the observation that mtDNA diversity cannot be interpreted without
      consideration of pest control and, possibly, the evolution of rodenticide
      resistance. However, demographic models explored by forward-time simulations
      cannot fully explain the low mtDNA diversity of European rats and lack of
      haplotype sharing with their source from Asia. Comprehensive nuclear marker
      analyses of a larger sample of Norway rats representing the world are needed to
      better resolve the evolutionary history of wild rats and of laboratory rats, as
      well as to better understand the evolution of anticoagulant resistance.

PMID- 24586323
TI  - Brief parenteral nutrition accelerates weight gain, head growth even in healthy
      VLBWs.
AB  - INTRODUCTION: Whether parenteral nutrition benefits growth of very low birth
      weight (VLBW) preterm infants in the setting of rapid enteral feeding advancement
      is unclear. Our aim was to examine this issue using data from Japan, where
      enteral feeding typically advances at a rapid rate. METHODS: We studied 4005
      hospitalized VLBW, very preterm (23-32 weeks' gestation) infants who reached full
      enteral feeding (100 ml/kg/day) by day 14, from 75 institutions in the Neonatal
      Research Network Japan (2003-2007). Main outcomes were weight gain, head growth,
      and extra-uterine growth restriction (EUGR, measurement <10(th) percentile for
      postmenstrual age) at discharge. RESULTS: 40% of infants received parenteral
      nutrition. Adjusting for maternal, infant, and institutional characteristics,
      infants who received parenteral nutrition had greater weight gain [0.09 standard
      deviation (SD), 95% CI: 0.02, 0.16] and head growth (0.16 SD, 95% CI: 0.05,
      0.28); lower odds of EUGR by head circumference (OR 0.66, 95% CI: 0.49, 0.88). No
      statistically significant difference was seen in the proportion of infants with
      EUGR at discharge. SGA infants and infants who took more than a week until full
      feeding had larger estimates. DISCUSSION: Even in infants who are able to
      establish enteral nutrition within 2 weeks, deprivation of parenteral nutrition
      in the first weeks of life could lead to under nutrition, but infants who reached
      full feeding within one week benefit least. It is important to predict which
      infants are likely or not likely to advance on enteral feedings within a week and
      balance enteral and parenteral nutrition for these infants.

PMID- 24586327
TI  - Improving population-level maternal health: a hard nut to crack? Long term
      findings and reflections on a 16-community randomised trial in Australia to
      improve maternal emotional and physical health after birth [ISRCTN03464021].
AB  - BACKGROUND: Community level interventions to improve maternal and child health
      have been supported and well evaluated in resource poor settings, but less so in
      developed countries. PRISM--Program of Resources, Information and Support for
      Mothers--was a primary care and community-based cluster-randomised trial in
      sixteen municipalities in Victoria, Australia, which aimed to reduce depression
      in mothers and improve their physical health. The aim of this paper is to report
      the longer term outcomes of PRISM and to reflect on lessons learned from this
      universal community intervention to improve maternal health. METHODS: Maternal
      health outcome data in PRISM were collected by postal questionnaire at six months
      and two years. At two years, the main outcome measures included the Edinburgh
      Postnatal Depression Scale (EPDS) and the SF-36. Secondary outcome measures
      included the Experience of Motherhood Scale (EOM) and the Parenting Stress Index
      (PSI). A primary intention to treat analysis was conducted, adjusting for the
      randomisation by cluster. RESULTS: 7,169/18,424 (39%) women responded to the
      postal questionnaire at two years -3,894 (40%) in the intervention arm and 3,275
      (38%) in the comparison arm. Respondents were mostly representative on available
      population data comparisons. There were no differences in depression prevalence
      (EPDS>=13) between the intervention and comparison arms (13.4% vs 13.1%; ORadj =
      1.06, 95%CI 0.91-1.24). Nor did women's mental health (MCS: 48.6 vs 49.1) or
      physical health scores (PCS: 49.1 vs 49.0) on the SF-36 differ between the trial
      arms. CONCLUSION: Improvement in maternal mental and physical health outcomes at
      the population level in the early years after childbirth remains a largely unmet
      challenge. Despite the lack of effectiveness of PRISM intervention strategies,
      important lessons about systems change, sustained investment and contextual
      understanding of the workability of intervention strategies can be drawn from the
      experience of PRISM. Trial Registration. Controlled-Trials.com ISRCTN03464021.

PMID- 24586328
TI  - An integrated framework for assessing vulnerability to climate change and
      developing adaptation strategies for coffee growing families in Mesoamerica.
AB  - The Mesoamerican region is considered to be one of the areas in the world most
      vulnerable to climate change. We developed a framework for quantifying the
      vulnerability of the livelihoods of coffee growers in Mesoamerica at regional and
      local levels and identify adaptation strategies. Following the Intergovernmental
      Panel on Climate Change (IPCC) concepts, vulnerability was defined as the
      combination of exposure, sensitivity and adaptive capacity. To quantify exposure,
      changes in the climatic suitability for coffee and other crops were predicted
      through niche modelling based on historical climate data and locations of coffee
      growing areas from Mexico, Guatemala, El Salvador and Nicaragua. Future climate
      projections were generated from 19 Global Circulation Models. Focus groups were
      used to identify nine indicators of sensitivity and eleven indicators of adaptive
      capacity, which were evaluated through semi-structured interviews with 558 coffee
      producers. Exposure, sensitivity and adaptive capacity were then condensed into
      an index of vulnerability, and adaptation strategies were identified in
      participatory workshops. Models predict that all target countries will experience
      a decrease in climatic suitability for growing Arabica coffee, with highest
      suitability loss for El Salvador and lowest loss for Mexico. High vulnerability
      resulted from loss in climatic suitability for coffee production and high
      sensitivity through variability of yields and out-migration of the work force.
      This was combined with low adaptation capacity as evidenced by poor post harvest
      infrastructure and in some cases poor access to credit and low levels of social
      organization. Nevertheless, the specific contributors to vulnerability varied
      strongly among countries, municipalities and families making general trends
      difficult to identify. Flexible strategies for adaption are therefore needed.
      Families need the support of government and institutions specialized in impacts
      of climate change and strengthening of farmer organizations to enable the
      adjustment of adaptation strategies to local needs and conditions. 

PMID- 24586329
TI  - Regional-scale migrations and habitat use of juvenile lemon sharks (Negaprion
      brevirostris) in the US South Atlantic.
AB  - Resolving the geographic extent and timing of coastal shark migrations, as well
      as their environmental cues, is essential for refining shark management
      strategies in anticipation of increasing anthropogenic stressors to coastal
      ecosystems. We employed a regional-scale passive acoustic telemetry array
      encompassing 300 km of the east Florida coast to assess what factors influence
      site fidelity of juvenile lemon sharks (Negaprion brevirostris) to an exposed
      coastal nursery at Cape Canaveral, and to document the timing and rate of their
      seasonal migrations. Movements of 54 juvenile lemon sharks were monitored for
      three years with individuals tracked for up to 751 days. While most sharks
      demonstrated site fidelity to the Cape Canaveral region December through February
      under typical winter water temperatures, historically extreme declines in ocean
      temperature were accompanied by rapid and often temporary, southward
      displacements of up to 190 km along the Florida east coast. From late February
      through April each year, most sharks initiated a northward migration at speeds of
      up to 64 km day(-1) with several individuals then detected in compatible
      estuarine telemetry arrays in Georgia and South Carolina up to 472 km from
      release locations. Nineteen sharks returned for a second or even third
      consecutive winter, thus demonstrating strong seasonal philopatry to the Cape
      Canaveral region. The long distance movements and habitat associations of
      immature lemon sharks along the US southeast coast contrast sharply with the
      natal site fidelity observed in this species at other sites in the western
      Atlantic Ocean. These findings validate the existing multi-state management
      strategies now in place. Results also affirm the value of collaborative passive
      arrays for resolving seasonal movements and habitat preferences of migratory
      coastal shark species not easily studied with other tagging techniques. 

PMID- 24586330
TI  - Prognostic value of stem cell quantification in stage II colon cancer.
AB  - BACKGROUND: Cancer stem cells (CSCs) are a subset of tumor cells with capacity to
      self-renew and generate the diverse cells that make up the tumor. The aim of this
      study is to evaluate the prognostic value of CSCs in a highly homogeneous
      population of stage II colon cancer. METHODS: One hundred stage II colon cancer
      patients treated by the same surgical team between 1977 and 2005 were
      retrospectively analyzed. None of the patients received adjuvant chemotherapy.
      Inmunohistochemistry expression of CD133, NANOG and CK20 was scored, using four
      levels: <10%, 11-25%, 26-50% and >50% positivity. Kaplan-Meier analysis and log
      rank test were used to compare survival. RESULTS: The average patient age was 68
      years (patients were between 45-92 years of age) and median follow up was 5.8
      years. There was recurrent disease in 17 (17%); CD133 expression (defined by >10%
      positivity) was shown in 60% of the tumors, in 95% for NANOG and 78% for CK20. No
      correlation was found among expression levels of CD133, NANOG or CK20 and relapse
      free survival (RFS) or overall survival (OS). However, a statistical significant
      correlation was found between established pathological prognostic factors and RFS
      and OS. CONCLUSIONS: Stem Cell quantification defined by CD133 and NANOG
      expression has no correlation with RFS or OS in this cohort of Stage II colon
      cancer.

PMID- 24586331
TI  - Alterations of mass density and 3D osteocyte lacunar properties in bisphosphonate
      related osteonecrotic human jaw bone, a synchrotron uCT study.
AB  - Osteonecrosis of the jaw, in association with bisphosphonates (BRONJ) used for
      treating osteoporosis or cancer, is a severe and most often irreversible side
      effect whose underlying pathophysiological mechanisms remain largely unknown.
      Osteocytes are involved in bone remodeling and mineralization where they
      orchestrate the delicate equilibrium between osteoclast and osteoblast activity
      and through the active process called osteocytic osteolysis. Here, we
      hypothesized that (i) changes of the mineralized tissue matrix play a substantial
      role in the pathogenesis of BRONJ, and (ii) the osteocyte lacunar morphology is
      altered in BRONJ. Synchrotron uCT with phase contrast is an appropriate tool for
      assessing both the 3D morphology of the osteocyte lacunae and the bone matrix
      mass density. Here, we used this technique to investigate the mass density
      distribution and 3D osteocyte lacunar properties at the sub-micrometer scale in
      human bone samples from the jaw, femur and tibia. First, we compared healthy
      human jaw bone to human tibia and femur in order to assess the specific
      differences and address potential explanations of why the jaw bone is exclusively
      targeted by the necrosis as a side effect of BP treatment. Second, we
      investigated the differences between BRONJ and control jaw bone samples to detect
      potential differences which could aid an improved understanding of the course of
      BRONJ. We found that the apparent mass density of jaw bone was significantly
      smaller compared to that of tibia, consistent with a higher bone turnover in the
      jaw bone. The variance of the lacunar volume distribution was significantly
      different depending on the anatomical site. The comparison between BRONJ and
      control jaw specimens revealed no significant increase in mineralization after
      BP. We found a significant decrease in osteocyte-lacunar density in the BRONJ
      group compared to the control jaw. Interestingly, the osteocyte-lacunar volume
      distribution was not altered after BP treatment. 

PMID- 24586332
TI  - Insights into the saliva of the brown marmorated stink bug Halyomorpha halys
      (Hemiptera: Pentatomidae).
AB  - We examined the salivary gland structure of the brown marmorated stink bug
      (Pentatomidae: Halyomorpha halys) and developed methods for independent
      collection of watery saliva and sheath saliva. This stink bug has become a
      serious invasive pest of agriculture in the United States and its saliva is
      largely responsible for the damage it causes. We determined by protein gel
      analysis and shotgun proteomics that the suite of proteins comprising the sheath
      and watery saliva are very distinct. Our results indicate that a substantial
      amount of sheath proteins are derived from tomato when stink bugs feed on tomato
      fruit. Consequently, the sheath saliva is comprised of both insect and plant
      derived proteins. Both sheath and watery saliva possessed amylase activities, but
      polyphenol oxidase and glucose oxidase activities were not detected in either
      saliva. Peroxidase activity was only detected in salivary sheaths, but only when
      stink bugs fed on tomato. Proteomic analysis indicated that the peroxidase was
      likely of plant origin. We also determined that sheath saliva, but not watery
      saliva elicited the jasmonate inducible defense gene proteinase inhibitor 2
      (Pin2), but this induction was only observed when sheaths had been collected from
      tomato. This indicates that the eliciting factor of the saliva is likely of plant
      origin. Lastly, neither watery or sheath saliva affected the expression of the
      salicylate inducible gene pathogenesis related gene (Pr1a-P4).

PMID- 24586333
TI  - Maternal plasma fetal DNA fractions in pregnancies with low and high risks for
      fetal chromosomal aneuploidies.
AB  - Recently published international guidelines recommend the clinical use of
      noninvasive prenatal test (NIPT) for aneuploidy screening only among pregnant
      women whose fetuses are deemed at high risk. The applicability of NIPT to
      aneuploidy screening among average risk pregnancies requires additional
      supportive evidence. A key determinant of the reliability of aneuploidy NIPT is
      the fetal DNA fraction in maternal plasma. In this report, we investigated if
      differences in fetal DNA fractions existed between different pregnancy risk
      groups. One hundred and ninety-five singleton pregnancies with male fetuses
      divided into 3 groups according to first trimester screening parameters were
      examined for fetal DNA percentage by counting Y chromosome DNA sequences using
      massively parallel sequencing. Fetal DNA fractions were compared between risk
      groups and assessed for correlations with first trimester screening parameters.
      There was no statistically significant difference in fetal DNA fractions across
      the high, intermediate and low risk groups. Fetal DNA fraction showed a strong
      negative correlation with maternal weight. Fetal DNA fraction also showed weak
      but significant correlations with gestational age, crown-rump length, multiple of
      medians of free beta-subunit of human chorionic gonadotropin and pregnancy
      associated plasma protein A. Similar fetal DNA fractions in maternal plasma
      between high, intermediate and low risk pregnant women is a precondition for
      uniform performance of the aneuploidy NIPTs for the general population. This
      study thus shows that the aneuploidy screening by NIPT is likely to offer similar
      analytical reliability without respect to the a priori fetal aneuploidy risk. 

PMID- 24586334
TI  - Single-cell states in the estrogen response of breast cancer cell lines.
AB  - Estrogen responsive breast cancer cell lines have been extensively studied to
      characterize transcriptional patterns in hormone-responsive tumors. Nevertheless,
      due to current technological limitations, genome-wide studies have typically been
      limited to population averaged data. Here we obtain, for the first time, a
      characterization at the single-cell level of the states and expression signatures
      of a hormone-starved MCF-7 cell system responding to estrogen. To do so, we
      employ a recently proposed model that allows for dissecting single-cell states
      from time-course microarray data. We show that within 32 hours following
      stimulation, MCF-7 cells traverse, most likely, six states, with a faster early
      response followed by a progressive deceleration. We also derive the genome-wide
      transcriptional profiles of such single-cell states and their functional
      characterization. Our results support a scenario where estrogen promotes cell
      cycle progression by controlling multiple, sequential regulatory steps, whose
      single-cell events are here identified. 

PMID- 24586335
TI  - Effects of multimicronutrient supplementation during pregnancy on postnatal
      growth of children under 5 years of age: a meta-analysis of randomized controlled
      trials.
AB  - BACKGROUND: The beneficial effect of antenatal multiple micronutrients
      supplementation on infant birth outcomes has been proposed by previous meta
      analyses. However, their benefits on postnatal health of children have not been
      summarized. A meta-analysis of randomized controlled trials was conducted to
      evaluate the effect of maternal multimicronutrient supplementation on postnatal
      growth of children under 5 years of age. METHODS: We searched both published and
      ongoing trials through the PubMed, EMBASE, CENTRAL (OVID platform), Web of
      Science, BIOSIS Previews, Chinese Science Citation Database, Scopus, ProQuest,
      ClinicalTrials.gov, Chinese Biomedical Database, and WANFANG database for
      randomized controlled trials. Reference lists of included studies and relevant
      reviews were also reviewed for eligible studies. Standard mean difference (SMD)
      was employed as the index for continuous variables by using fixed effects models.
      Trend analysis by visual inspection was applied to evaluate the change of mean
      difference of weight and height between the groups over time. RESULTS: Nine
      trials (12 titles) from nine different countries were retrieved for analysis.
      Pooled results showed that antenatal multimicronutrient supplementation increased
      child head circumference (SMD = 0.08, 95% CI: 0.00-0.15) compared with
      supplementation with two micronutrient or less. No evidence was found for the
      benefits of antenatal multimicronutrient supplementation on weight (P = 0.11),
      height (P = 0.66), weight-for-age z scores (WAZ) (P = 0.34), height-for-age z
      scores (HAZ) (P = 0.81) and weight-for-height z scores (WHZ) (P = 0.22). A
      positive effect was found on chest circumference based on two included studies.
      CONCLUSIONS: Antenatal multimicronutrient supplementation has a significant
      positive effect on head circumference of children under 5 years. No impact of the
      supplementation was found on weight, height, WAZ, HAZ and WHZ.

PMID- 24586336
TI  - A novel toxicokinetic modeling of cypermethrin and permethrin and their
      metabolites in humans for dose reconstruction from biomarker data.
AB  - To assess exposure to pyrethroids in the general population, one of most widely
      used method nowadays consists of measuring urinary metabolites. Unfortunately,
      interpretation of data is limited by the unspecified relation between dose and
      levels in biological tissues and excreta. The objective of this study was to
      develop a common multi-compartment toxicokinetic model to predict the time
      courses of two mainly used pyrethroid pesticides, permethrin and cypermethrin,
      and their metabolites (cis-DCCA, trans-DCCA and 3-PBA) in the human body and in
      accessible biological matrices following different exposure scenarios.
      Toxicokinetics was described mathematically by systems of differential equations
      to yield the time courses of these pyrethroids and their metabolites in the
      different compartments. Unknown transfer rate values between compartments were
      determined from best fits to available human data on the urinary excretion time
      courses of metabolites following an oral and dermal exposure to cypermethrin in
      volunteers. Since values for these coefficients have not yet been determined, a
      mathematical routine was programmed in MathCad to establish the possible range of
      values on the basis of physiological and mathematical considerations. The best
      combination of parameter values was then selected using a statistic measure
      (reliability factor) along with a statistically acceptable range of values for
      each parameter. With this approach, simulations provided a close approximation to
      published time course data. This model allows to predict urinary time courses of
      trans-DCCA, cis-DCCA and 3-PBA, whatever the exposure route. It can also serve to
      reconstruct absorbed doses of permethrin or cypermethrin in the population using
      measured biomarker data. 

PMID- 24586337
TI  - Student attainment of proficiency in a clinical skill: the assessment of
      individual learning curves.
AB  - The aims of this study were to determine if the learning curve cumulative
      summation test (LC-CUSUM) can differentiate proficiency in placing intravenous
      catheters by novice learners, and identify the cause of failure when it occurred.
      In a prospective, observational study design 6 undergraduate students with no
      previous experience of placing intravenous catheters received standardized
      training by a board certified veterinary anesthesiologist in intravenous catheter
      placement technique. Immediately following training, each student attempted 60
      intravenous catheterizations in a dog mannequin thoracic limb model. Results were
      scored as a success or failure based upon completion of four specific criteria,
      and where catheter placement failure occurred, the cause was recorded according
      to pre-defined criteria. Initial acceptable and unacceptable failure rates were
      set by the study team and the LC-CUSUM was used to generate a learning curve for
      each student. Using 10% and 25% acceptable and unacceptable failure rates, 3 out
      of 6 students attained proficiency, requiring between 26 to 48 attempts. Applying
      25% and 50% acceptable and unacceptable failure rates, 5 of 6 students obtained
      proficiency, requiring between 18 and 55 attempts. Wide inter-individual
      variability was observed and the majority of failed catheterisation attempts were
      limited to two of the four pre-defined criteria. These data indicate that the LC
      CUSUM can be used to generate individual learning curves, inter-individual
      variability in catheter placement ability is wide, and that specific steps in
      catheter placement are responsible for the majority of failures. These findings
      may have profound implications for how we teach and assess technical skills. 

PMID- 24586338
TI  - Modeling TGF-beta in early stages of cancer tissue dynamics.
AB  - Recent works have highlighted a double role for the Transforming Growth Factor
      beta (TGF-beta): it inhibits cancer in healthy cells and potentiates tumor
      progression during late stage of tumorigenicity, respectively; therefore it has
      been termed the "Jekyll and Hyde" of cancer or, alternatively, an "excellent
      servant but a bad master". It remains unclear how this molecule could have the
      two opposite behaviours. In this work, we propose a TGF-beta multi scale
      mathematical model at molecular, cellular and tissue scales. The multi scalar
      behaviours of the TGF-beta are described by three coupled models built up
      together which can approximatively be related to distinct microscopic,
      mesoscopic, and macroscopic scales, respectively. We first model the dynamics of
      TGF-beta at the single-cell level by taking into account the intracellular and
      extracellular balance and the autocrine and paracrine behaviour of TGF-beta. Then
      we use the average estimates of the TGF-beta from the first model to understand
      its dynamics in a model of duct breast tissue. Although the cellular model and
      the tissue model describe phenomena at different time scales, their cumulative
      dynamics explain the changes in the role of TGF-beta in the progression from
      healthy to pre-tumoral to cancer. We estimate various parameters by using
      available gene expression datasets. Despite the fact that our model does not
      describe an explicit tissue geometry, it provides quantitative inference on the
      stage and progression of breast cancer tissue invasion that could be compared
      with epidemiological data in literature. Finally in the last model, we
      investigated the invasion of breast cancer cells in the bone niches and the
      subsequent disregulation of bone remodeling processes. The bone model provides an
      effective description of the bone dynamics in healthy and early stages cancer
      conditions and offers an evolutionary ecological perspective of the dynamics of
      the competition between cancer and healthy cells.

PMID- 24586339
TI  - CTRP2 overexpression improves insulin and lipid tolerance in diet-induced obese
      mice.
AB  - CTRP2 is a secreted plasma protein of the C1q family that enhances glycogen
      deposition and fat oxidation in cultured myotubes. Its in vivo metabolic
      function, however, has not been established. We show here that acute and chronic
      metabolic perturbations induced by fasting or high-fat feeding up-regulated the
      mRNA expression of Ctrp2 in white adipose tissue without affecting its
      circulating plasma levels. We generated a transgenic mouse model with elevated
      circulating levels of CTRP2 to determine its metabolic function in vivo. When fed
      a low-fat diet, wild-type and CTRP2 transgenic mice exhibited no metabolic
      phenotypes. When challenged with a high-fat diet to induce obesity, wild-type and
      CTRP2 transgenic mice had similar weight gain, adiposity, food intake, metabolic
      rate, and energy expenditure. Fasting serum lipid and adipokine profiles were
      also similar between the two groups of mice. However, while glucose and insulin
      levels in the fasted state were comparable between wild-type and CTRP2 transgenic
      mice, insulin levels in the fed state were consistently lower in transgenic mice.
      Notably, CTRP2 transgenic mice had improved insulin tolerance and a greater
      capacity to handle acute lipid challenge relative to littermate controls. Our
      results highlight, for the first time, the in vivo role of CTRP2 in modulating
      whole-body metabolism.

PMID- 24586340
TI  - Alanine-glyoxylate aminotransferase 2 (AGXT2) polymorphisms have considerable
      impact on methylarginine and beta-aminoisobutyrate metabolism in healthy
      volunteers.
AB  - Elevated plasma concentrations of asymmetric (ADMA) and symmetric (SDMA)
      dimethylarginine have repeatedly been linked to adverse clinical outcomes. Both
      methylarginines are substrates of alanine-glyoxylate aminotransferase 2 (AGXT2).
      It was the aim of the present study to simultaneously investigate the functional
      relevance and relative contributions of common AGXT2 single nucleotide
      polymorphisms (SNPs) to plasma and urinary concentrations of methylarginines as
      well as beta-aminoisobutyrate (BAIB), a prototypic substrate of AGXT2. In a
      cohort of 400 healthy volunteers ADMA, SDMA and BAIB concentrations were
      determined in plasma and urine using HPLC-MS/MS and were related to the coding
      AGXT2 SNPs rs37369 (p.Val140Ile) and rs16899974 (p.Val498Leu). Volunteers
      heterozygous or homozygous for the AGXT2 SNP rs37369 had higher SDMA plasma
      concentrations by 5% and 20% (p = 0.002) as well as higher BAIB concentrations by
      54% and 146%, respectively, in plasma and 237% and 1661%, respectively, in urine
      (both p<0.001). ADMA concentrations were not affected by both SNPs. A haplotype
      analysis revealed that the second investigated AGXT2 SNP rs16899974, which was
      not significantly linked to the other AGXT2 SNP, further aggravates the effect of
      rs37369 with respect to BAIB concentrations in plasma and urine. To investigate
      the impact of the amino acid exchange p.Val140Ile, we established human embryonic
      kidney cell lines stably overexpressing wild-type or mutant (p.Val140Ile) AGXT2
      protein and assessed enzyme activity using BAIB and stable-isotope labeled [2H6]
      SDMA as substrate. In vitro, the amino acid exchange of the mutant protein
      resulted in a significantly lower enzyme activity compared to wild-type AGXT2
      (p<0.05). In silico modeling of the SNPs indicated reduced enzyme stability and
      substrate binding. In conclusion, SNPs of AGXT2 affect plasma as well as urinary
      BAIB and SDMA concentrations linking methylarginine metabolism to the common
      genetic trait of hyper-beta-aminoisobutyric aciduria.

PMID- 24586341
TI  - The kick-in system: a novel rapid knock-in strategy.
AB  - Knock-in mouse models have contributed tremendously to our understanding of human
      disorders. However, generation of knock-in animals requires a significant
      investment of time and effort. We addressed this problem by developing a novel
      knock-in system that circumvents several traditional challenges by establishing
      stem cells with acceptor elements enveloping a particular genomic target. Once
      established, these acceptor embryonic stem (ES) cells are efficient at
      directionally incorporating mutated target DNA using modified Cre/lox technology.
      This is advantageous, because knock-ins are not restricted to one a priori
      selected variation. Rather, it is possible to generate several mutant animal
      lines harboring desired alterations in the targeted area. Acceptor ES cell
      generation is the rate-limiting step, lasting approximately 2 months. Subsequent
      manipulations toward animal production require an additional 8 weeks, but this
      delimits the full period from conception of the genetic alteration to its animal
      incorporation. We call this system a "kick-in" to emphasize its unique
      characteristics of speed and convenience. To demonstrate the functionality of the
      kick-in methodology, we generated two mouse lines with separate mutant versions
      of the voltage-dependent potassium channel Kv7.2 (Kcnq2): p.Tyr284Cys (Y284C) and
      p.Ala306Thr (A306T); both variations have been associated with benign familial
      neonatal epilepsy. Adult mice homozygous for Y284C, heretofore unexamined in
      animals, presented with spontaneous seizures, whereas A306T homozygotes died
      early. Heterozygous mice of both lines showed increased sensitivity to
      pentylenetetrazole, possibly due to a reduction in M-current in CA1 hippocampal
      pyramidal neurons. Our observations for the A306T animals match those obtained
      with traditional knock-in technology, demonstrating that the kick-in system can
      readily generate mice bearing various mutations, making it a suitable feeder
      technology toward streamlined phenotyping. 

PMID- 24586342
TI  - Change of body weight and macrophage inhibitory cytokine-1 during chemotherapy in
      advanced gastric cancer: what is their clinical significance?
AB  - BACKGROUND: Weight loss in advanced gastric cancer (GC) has been widely
      acknowledged to be a predictor for poor survival. However, very few studies have
      investigated the weight loss that occurs during chemotherapy. Therefore, we
      focused on weight loss during chemotherapy in patients with advanced GC and
      investigated the concentrations of macrophage inhibitory cytokine-1 (MIC-1),
      which has been recognized as a probable etiological factor in anorexia and weight
      loss. METHODS: We analyzed 384 patients with inoperable locally advanced or
      metastatic GC receiving first-line chemotherapy. Patients were assigned to one of
      two groups on the basis of their weight change during chemotherapy: >3% weight
      loss and <= 3% weight loss. Serum MIC-1 and C-reactive protein (CRP)
      concentrations were also assessed in these patients. RESULTS: The >3% weight loss
      group had shorter overall survival (OS; 12.0 months vs. 17.5 months, P = 0.000)
      than the <= 3% weight loss group, and the survival rates improved if the weight
      loss was reversed during chemotherapy. Although the MIC-1 concentrations were not
      correlated with weight loss before (P = 0.156) or during chemotherapy (P =
      0.164), it correlated significantly with the CRP concentration (P = 0.001).
      Furthermore, elevated MIC-1 concentrations before chemotherapy (P = 0.017) and
      increased MIC-1 concentrations during chemotherapy (P = 0.001) were both found to
      be predictors of poor OS. CONCLUSIONS: Changes in the body weight during
      chemotherapy could influence the prognosis in patients with advanced GC, and the
      MIC-1 might be a potential predictive and prognostic biomarker in those patients.

PMID- 24586343
TI  - Distinct roles for inhibition in spatial and temporal tuning of local edge
      detectors in the rabbit retina.
AB  - This paper examines the role of inhibition in generating the receptive-field
      properties of local edge detector (LED) ganglion cells in the rabbit retina. We
      confirm that the feed-forward inhibition is largely glycinergic but, contrary to
      a recent report, our data demonstrate that the glycinergic inhibition contributes
      to temporal tuning for the OFF and ON inputs to the LEDs by delaying the onset of
      spiking; this delay was more pronounced for the ON inputs (~ 340 ms) than the OFF
      inputs (~ 12 ms). Blocking glycinergic transmission reduced the delay to spike
      onset and increased the responses to flickering stimuli at high frequencies.
      Analysis of the synaptic conductances indicates that glycinergic amacrine cells
      affect temporal tuning through both postsynaptic inhibition of the LEDs and
      presynaptic modulation of the bipolar cells that drive the LEDs. The results also
      confirm that presynaptic GABAergic transmission contributes significantly to the
      concentric surround antagonism in LEDs; however, unlike presumed LEDs in the
      mouse retina, the surround is only partly generated by spiking amacrine cells.

PMID- 24586344
TI  - Realistic three dimensional fitness landscapes generated by self organizing maps
      for the analysis of experimental HIV-1 evolution.
AB  - Human Immunodeficiency Virus type 1 (HIV-1) because of high mutation rates, large
      population sizes, and rapid replication, exhibits complex evolutionary
      strategies. For the analysis of evolutionary processes, the graphical
      representation of fitness landscapes provides a significant advantage. The
      experimental determination of viral fitness remains, in general, difficult and
      consequently most published fitness landscapes have been artificial, theoretical
      or estimated. Self-Organizing Maps (SOM) are a class of Artificial Neural Network
      (ANN) for the generation of topological ordered maps. Here, three-dimensional
      (3D) data driven fitness landscapes, derived from a collection of sequences from
      HIV-1 viruses after "in vitro" passages and labelled with the corresponding
      experimental fitness values, were created by SOM. These maps were used for the
      visualization and study of the evolutionary process of HIV-1 "in vitro" fitness
      recovery, by directly relating fitness values with viral sequences. In addition
      to the representation of the sequence space search carried out by the viruses,
      these landscapes could also be applied for the analysis of related variants like
      members of viral quasiespecies. SOM maps permit the visualization of the complex
      evolutionary pathways in HIV-1 fitness recovery. SOM fitness landscapes have an
      enormous potential for the study of evolution in related viruses of "in vitro"
      works or from "in vivo" clinical studies with human, animal or plant viral
      infections. 

PMID- 24586345
TI  - De novo assembly of a transcriptome for Calanus finmarchicus (Crustacea,
      Copepoda)--the dominant zooplankter of the North Atlantic Ocean.
AB  - Assessing the impact of global warming on the food web of the North Atlantic will
      require difficult-to-obtain physiological data on a key copepod crustacean,
      Calanus finmarchicus. The de novo transcriptome presented here represents a new
      resource for acquiring such data. It was produced from multiplexed gene libraries
      using RNA collected from six developmental stages: embryo, early nauplius (NI
      II), late nauplius (NV-VI), early copepodite (CI-II), late copepodite (CV) and
      adult (CVI) female. Over 400,000,000 paired-end reads (100 base-pairs long) were
      sequenced on an Illumina instrument, and assembled into 206,041 contigs using
      Trinity software. Coverage was estimated to be at least 65%. A reference
      transcriptome comprising 96,090 unique components ("comps") was annotated using
      Blast2GO. 40% of the comps had significant blast hits. 11% of the comps were
      successfully annotated with gene ontology (GO) terms. Expression of many comps
      was found to be near zero in one or more developmental stages suggesting that 35
      to 48% of the transcriptome is "silent" at any given life stage. Transcripts
      involved in lipid biosynthesis pathways, critical for the C. finmarchicus life
      cycle, were identified and their expression pattern during development was
      examined. Relative expression of three transcripts suggests wax ester
      biosynthesis in late copepodites, but triacylglyceride biosynthesis in adult
      females. Two of these transcripts may be involved in the preparatory phase of
      diapause. A key environmental challenge for C. finmarchicus is the seasonal
      exposure to the dinoflagellate Alexandrium fundyense with high concentrations of
      saxitoxins, neurotoxins that block voltage-gated sodium channels. Multiple
      contigs encoding putative voltage-gated sodium channels were identified. They
      appeared to be the result of both alternate splicing and gene duplication. This
      is the first report of multiple NaV1 genes in a protostome. These data provide
      new insights into the transcriptome and physiology of this environmentally
      important zooplankter. 

PMID- 24586346
TI  - Poly(trimethylene carbonate-co-epsilon-caprolactone) promotes axonal growth.
AB  - Mammalian central nervous system (CNS) neurons do not regenerate after injury due
      to the inhibitory environment formed by the glial scar, largely constituted by
      myelin debris. The use of biomaterials to bridge the lesion area and the creation
      of an environment favoring axonal regeneration is an appealing approach,
      currently under investigation. This work aimed at assessing the suitability of
      three candidate polymers - poly(epsilon-caprolactone), poly(trimethylene
      carbonate-co-epsilon-caprolactone) (P(TMC-CL)) (11?89 mol%) and poly(trimethylene
      carbonate) - with the final goal of using these materials in the development of
      conduits to promote spinal cord regeneration. Poly(L-lysine) (PLL) coated
      polymeric films were tested for neuronal cell adhesion and neurite outgrowth. At
      similar PLL film area coverage conditions, neuronal polarization and axonal
      elongation was significantly higher on P(TMC-CL) films. Furthermore, cortical
      neurons cultured on P(TMC-CL) were able to extend neurites even when seeded onto
      myelin. This effect was found to be mediated by the glycogen synthase kinase
      3beta (GSK3beta) signaling pathway with impact on the collapsin response mediator
      protein 4 (CRMP4), suggesting that besides surface topography, nanomechanical
      properties were implicated in this process. The obtained results indicate P(TMC
      CL) as a promising material for CNS regenerative applications as it promotes
      axonal growth, overcoming myelin inhibition. 

PMID- 24586347
TI  - Do capuchin monkeys (Cebus apella) diagnose causal relations in the absence of a
      direct reward?
AB  - We adapted a method from developmental psychology to explore whether capuchin
      monkeys (Cebus apella) would place objects on a "blicket detector" machine to
      diagnose causal relations in the absence of a direct reward. Across five
      experiments, monkeys could place different objects on the machine and obtain
      evidence about the objects' causal properties based on whether each object
      "activated" the machine. In Experiments 1-3, monkeys received both audiovisual
      cues and a food reward whenever the machine activated. In these experiments,
      monkeys spontaneously placed objects on the machine and succeeded at
      discriminating various patterns of statistical evidence. In Experiments 4 and 5,
      we modified the procedure so that in the learning trials, monkeys received the
      audiovisual cues when the machine activated, but did not receive a food reward.
      In these experiments, monkeys failed to test novel objects in the absence of an
      immediate food reward, even when doing so could provide critical information
      about how to obtain a reward in future test trials in which the food reward
      delivery device was reattached. The present studies suggest that the gap between
      human and animal causal cognition may be in part a gap of motivation.
      Specifically, we propose that monkey causal learning is motivated by the desire
      to obtain a direct reward, and that unlike humans, monkeys do not engage in
      learning for learning's sake.

PMID- 24586348
TI  - Quantitative CT variables enabling response prediction in neoadjuvant therapy
      with EGFR-TKIs: are they different from those in neoadjuvant concurrent
      chemoradiotherapy?
AB  - BACKGROUND AND PURPOSE: To correlate changes of various CT parameters after the
      neoadjuvant treatment in patients with lung adenocarcinoma with pathologic
      responses, focused on their relationship with different therapeutic options,
      particularly of EGFR-TKI and concurrent chemoradiation therapy (CCRT) settings.
      MATERIALS AND METHODS: We reviewed pre-operative CT images of primary tumors and
      surgical specimens obtained after neoadjuvant therapy (TKI, n = 23; CCRT, n = 28)
      from 51 patients with lung adenocarcinoma. Serial changes in tumor volume,
      density, mass, skewness/kurtosis, and size-zone variability/intensity
      variability) were assessed from CT datasets. The changes in CT parameters were
      correlated with histopathologic responses, and the relationship between CT
      variables and histopathologic responses was compared between TKI and CCRT groups.
      RESULTS: Tumor volume, mass, kurtosis, and skewness were significant predictors
      of pathologic response in CCRT group in univariate analysis. Using multivariate
      analysis, kurtosis was found to be independent predictor. In TKI group, intensity
      variability and size-zone variability were significantly decreased in pathologic
      responder group. Intensity variability was found to be an independent predictor
      for pathologic response on multivariate analysis. CONCLUSIONS: Quantitative CT
      variables including histogram or texture analysis have potential as a predictive
      tool for response evaluation, and it may better reflect treatment response than
      standard response criteria based on size changes.

PMID- 24586349
TI  - Evaluation of the efficacy and safety of a marine-derived Bacillus strain for use
      as an in-feed probiotic for newly weaned pigs.
AB  - Forty eight individual pigs (8.7+/-0.26 kg) weaned at 28+/-1 d of age were used
      in a 22-d study to evaluate the effect of oral administration of a Bacillus
      pumilus spore suspension on growth performance and health indicators. Treatments
      (n = 16) were: (1) non-medicated diet; (2) medicated diet with apramycin (200
      mg/kg) and pharmacological levels of zinc oxide (2,500 mg zinc/kg) and (3) B.
      pumilus diet (non-medicated diet + 10(10) spores/day B. pumilus). Final body
      weight and average daily gain tended to be lower (P = 0.07) and feed conversion
      ratio was worsened (P<0.05) for the medicated treatment compared to the B.
      pumilus treatment. Ileal E. coli counts were lower for the B. pumilus and
      medicated treatments compared to the non-medicated treatment (P<0.05), perhaps as
      a result of increased ileal propionic acid concentrations (P<0.001). However, the
      medicated treatment reduced fecal (P<0.001) and cecal (P<0.05) Lactobacillus
      counts and tended to reduce the total cecal short chain fatty acid (SCFA)
      concentration (P = 0.10). Liver weights were lighter and concentrations of liver
      enzymes higher (P<0.05) in pigs on the medicated treatment compared to those on
      the non-medicated or B. pumilus treatments. Pigs on the B. pumilus treatment had
      lower overall lymphocyte and higher granulocyte percentages (P<0.001) and higher
      numbers of jejunal goblet cells (P<0.01) than pigs on either of the other two
      treatments or the non-medicated treatment, respectively. However,
      histopathological examination of the small intestine, kidneys and liver revealed
      no abnormalities. Overall, the B. pumilus treatment decreased ileal E. coli
      counts in a manner similar to the medicated treatment but without the adverse
      effects on growth performance, Lactobacillus counts, cecal SCFA concentration and
      possible liver toxicity experienced with the medicated treatment. 

PMID- 24586350
TI  - Darbepoetin alpha reduces oxidative stress and chronic inflammation in
      atherosclerotic lesions of apo E deficient mice in experimental renal failure.
AB  - BACKGROUND: Cardiovascular morbidity and mortality is very important in patients
      with chronic renal failure. This occurs even in mild impairment of renal function
      and may be related to oxidative stress and chronic inflammation. The
      nephrectomized apo E knockout mouse is an accepted model for evaluating
      atherosclerosis in renal dysfunction. Erythropoietin derivates showed anti
      oxidative and anti-inflammatory effects. Therefore, this study evaluates the
      effects of Darbepoetin on markers of oxidative stress and chronic inflammation in
      atherosclerotic lesions in apo E knockout mice with renal dysfunction. METHODS:
      Apo E knockout mice underwent unilateral (Unx, n = 20) or subtotal (Snx, n = 26)
      nephrectomy or sham operation (Sham, n = 16). Mice of each group were either
      treated with Darbepoetin or saline solution, a part of Snx mice received a
      tenfold higher dose of Darbepoetin. The aortic plaques were measured and
      morphologically characterized. Additional immunhistochemical analyses were
      performed on tissue samples taken from the heart and the aorta. RESULTS: Both Unx
      and Snx mice showed increased expression of markers of oxidative stress and
      chronic inflammation. While aortic plaque size was not different, Snx mice showed
      advanced plaque stages when compared to Unx mice. Darbepoetin treatment elevated
      hematocrit and lowered Nitrotyrosin as one marker of oxidative stress,
      inflammation in heart and aorta, plaque stage and in the high dose even plaque
      cholesterol content. In contrast, there was no influence of Darbepoetin on aortic
      plaque size; high dose Darbepoetin treatment resulted in elevated renal serum
      parameters. CONCLUSION: Darbepoetin showed some protective cardiovascular effects
      irrespective of renal function, i.e. it improved plaque structure and reduced
      some signs of oxidative stress and chronic inflammation without affecting plaque
      size. Nevertheless, the dose dependent adverse effects must be considered as high
      Darbepoetin treatment elevated serum urea. Elevation of hematocrit might be a
      favorable effect in anemic Snx animals but a thrombogenic risk in Sham animals.

PMID- 24586352
TI  - A population survey of the glucose-6-phosphate dehydrogenase (G6PD) 563C>T
      (Mediterranean) mutation in Afghanistan.
AB  - Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common inherited enzyme
      defect and an important problem in areas with Plasmodium vivax infection because
      of the risk of haemolysis following administration of primaquine to treat the
      liver forms of the parasite. We undertook a genotypic survey of 713 male
      individuals across nine provinces of Afghanistan in which malaria is found, four
      in the north and five in the east. RFLP typing at nucleotide position 563
      detected 40 individuals with the Mediterranean mutation 563C>T, an overall
      prevalence of 5.6%. This varied according to self-reported ethnicity, with
      prevalence in the Pashtun/Pashai group of 33/369 (8.9%) compared to 7/344
      individuals in the rest of the population (2.0%; p<0.001, Chi-squared test).
      Multivariate analysis of ethnicity and geographical location indicated an
      adjusted odds ratio of 3.50 (95% CI 1.36-9.02) for the Pashtun/Pashai group,
      while location showed only a trend towards higher prevalence in eastern provinces
      (adjusted odds ratio = 1.73, 0.73-4.13). Testing of known polymorphic markers
      (1311C>T in exon 11, and C93T in intron XI) in a subset of 82 individuals wild
      type at C563 revealed a mixture of 3 haplotypes in the background population and
      was consistent with data from the 1000 Genomes Project and published studies. By
      comparison individuals with G6PD deficiency showed a highly skewed haplotype
      distribution, with 95% showing the CT haplotype, a finding consistent with
      relatively recent appearance and positive selection of the Mediterranean variant
      in Afghanistan. Overall, the data confirm that the Mediterranean variant of G6PD
      is common in many ethnic groups in Afghanistan, indicating that screening for
      G6PD deficiency is required in all individuals before radical treatment of P.
      vivax with primaquine.

PMID- 24586351
TI  - Comparable autoantibody serum levels against amyloid- and inflammation-associated
      proteins in Parkinson's disease patients and controls.
AB  - Naturally occurring autoantibodies (NAbs) against a number of potentially disease
      associated cellular proteins, including Amyloid-beta1-42 (Abeta1-42), Alpha
      synuclein (Asyn), myelin basic protein (MBP), myelin oligodendrocyte glycoprotein
      (MOG), and S100 calcium binding protein B (S100B) have been suggested to be
      associated with neurodegenerative disorders, in particular Alzheimer's (AD) and
      Parkinson's disease (PD). Whereas the (reduced) occurrence of specific NAbs in AD
      is widely accepted, previous literature examining the relation of these NAb
      titres between PD patients and controls, as well as comparing these levels with
      demographic and clinical parameters in PD patients have produced inconsistent
      findings. We therefore aimed, in a cross-sectional approach, to determine serum
      titres of the above NAbs in a cohort of 93 PD patients (31 of them demented) and
      194 controls. Levels were correlated with demographic and clinical variables,
      cerebrospinal fluid Abeta1-42, total tau and phospho-tau levels, as well as with
      single nucleotide polymorphisms (SNPs) of genes which either have been reported
      to influence the immune system, the amyloid cascade or the occurrence of PD
      (ApoE, GSK3B, HLA-DRA, HSPA5, SNCA, and STK39). The investigated NAb titres were
      neither significantly associated with the occurrence of PD, nor with demographic
      and clinical parameters, neurodegenerative markers or genetic variables. These
      results argue against a major potential of blood-borne parameters of the adaptive
      immune system to serve as trait or state markers in PD. 

PMID- 24586353
TI  - The 'dark side' and 'bright side' of personality: when too much conscientiousness
      and too little anxiety are detrimental with respect to the acquisition of medical
      knowledge and skill.
AB  - Theory suggests that personality traits evolved to have costs and benefits, with
      the effectiveness of a trait dependent on how these costs and benefits relate to
      the present circumstances. This suggests that traits that are generally viewed as
      positive can have a 'dark side' and those generally viewed as negative can have a
      'bright side' depending on changes in context. We test this in a sample of 220 UK
      medical students with respect to associations between the Big 5 personality
      traits and learning outcomes across the 5 years of a medical degree. The medical
      degree offers a changing learning context from pre-clinical years (where a more
      methodical approach to learning is needed) to the clinical years (where more
      flexible learning is needed, in a more stressful context). We argue that while
      trait conscientiousness should enhance pre-clinical learning, it has a 'dark
      side' reducing the acquisition of knowledge in the clinical years. We also
      suggest that anxiety has a 'bright side' enhancing the acquisition of skills in
      the clinical years. We also explore if intelligence enhances learning across the
      medical degree. Using confirmatory factor analysis and structural equation
      modelling we show that medical skills and knowledge assessed in the pre-clinical
      and clinical years are psychometrically distinguishable, forming a learning
      'backbone', whereby subsequent learning outcomes are predicted by previous ones.
      Consistent with our predictions conscientiousness enhanced preclinical knowledge
      acquisition but reduced the acquisition of clinical knowledge and anxiety
      enhanced the acquisition of clinical skills. We also identified a curvilinear U
      shaped association between Surgency (extraversion) and pre-clinical knowledge
      acquisition. Intelligence predicted initial clinical knowledge, and had a
      positive total indirect effect on clinical knowledge and clinical skill
      acquisition. For medical selection, this suggests that selecting students high on
      conscientiousness may be problematic, as it may be excluding those with some
      degree of moderate anxiety. 

PMID- 24586354
TI  - Love thy neighbour: automatic animal behavioural classification of acceleration
      data using the K-nearest neighbour algorithm.
AB  - Researchers hoping to elucidate the behaviour of species that aren't readily
      observed are able to do so using biotelemetry methods. Accelerometers in
      particular are proving particularly effective and have been used on terrestrial,
      aquatic and volant species with success. In the past, behavioural modes were
      detected in accelerometer data through manual inspection, but with developments
      in technology, modern accelerometers now record at frequencies that make this
      impractical. In light of this, some researchers have suggested the use of various
      machine learning approaches as a means to classify accelerometer data
      automatically. We feel uptake of this approach by the scientific community is
      inhibited for two reasons; 1) Most machine learning algorithms require selection
      of summary statistics which obscure the decision mechanisms by which
      classifications are arrived, and 2) they are difficult to implement without
      appreciable computational skill. We present a method which allows researchers to
      classify accelerometer data into behavioural classes automatically using a
      primitive machine learning algorithm, k-nearest neighbour (KNN). Raw acceleration
      data may be used in KNN without selection of summary statistics, and it is easily
      implemented using the freeware program R. The method is evaluated by detecting 5
      behavioural modes in 8 species, with examples of quadrupedal, bipedal and volant
      species. Accuracy and Precision were found to be comparable with other, more
      complex methods. In order to assist in the application of this method, the script
      required to run KNN analysis in R is provided. We envisage that the KNN method
      may be coupled with methods for investigating animal position, such as GPS
      telemetry or dead-reckoning, in order to implement an integrated approach to
      movement ecology research. 

PMID- 24586355
TI  - Friend or foe? Early social evaluation of human interactions.
AB  - We report evidence that 29-month-old toddlers and 10-month-old preverbal infants
      discriminate between two agents: a pro-social agent, who performs a positive
      (comforting) action on a human patient and a negative (harmful) action on an
      inanimate object, and an anti-social agent, who does the converse. The evidence
      shows that they prefer the former to the latter even though the agents perform
      the same bodily movements. Given that humans can cause physical harm to their
      conspecifics, we discuss this finding in light of the likely adaptive value of
      the ability to detect harmful human agents. 

PMID- 24586356
TI  - Phylogeographic structure in benthic marine invertebrates of the southeast
      Pacific coast of Chile with differing dispersal potential.
AB  - The role of dispersal potential on phylogeographic structure, evidenced by the
      degree of genetic structure and the presence of coincident genetic and
      biogeographic breaks, was evaluated in a macrogeographic comparative approach
      along the north-central coast of Chile, across the biogeographic transition zone
      at 30 degrees S. Using 2,217 partial sequences of the mitochondrial Cytochrome
      Oxidase I gene of eight benthic invertebrate species along ca. 2,600 km of coast,
      we contrasted dispersal potential with genetic structure and determined the
      concordance between genetic divergence between biogeographic regions and the
      biogeographic transition zone at 30 degrees S. Genetic diversity and
      differentiation highly differed between species with high and low dispersal
      potential. Dispersal potential, sometimes together with biogeographic region, was
      the factor that best explained the genetic structure of the eight species. The
      three low dispersal species, and one species assigned to the high dispersal
      category, had a phylogeographic discontinuity coincident with the biogeographic
      transition zone at 30 degrees S. Furthermore, coalescent analyses based on the
      isolation-with-migration model validate that the split between biogeographic
      regions north and south of 30 degrees S has a historic origin. The signatures of
      the historic break in high dispersers is parsimoniously explained by the
      homogenizing effects of gene flow that have erased the genetic signatures, if
      ever existed, in high dispersers. Of the four species with structure across the
      break, only two had significant albeit very low levels of asymmetric migration
      across the transition zone. Historic processes have led to the current
      biogeographic and phylogeographic structure of marine species with limited
      dispersal along the north-central coast of Chile, with a strong lasting impact in
      their genetic structure. 

PMID- 24586357
TI  - Hyaluronic acid receptor Stabilin-2 regulates Erk phosphorylation and arterial-
      venous differentiation in zebrafish.
AB  - The hyaluronic acid receptor for endocytosis Stabilin-2/HARE mediates systemic
      clearance of multiple glycosaminoglycans from the vascular and lymphatic
      circulations. In addition, recent in vitro studies indicate that Stab2 can
      participate in signal transduction by interacting with hyaluronic acid (HA),
      which results in Erk phosphorylation. However, it is not known whether Stab2
      function or HA-Stab2 signaling play any role in embryonic development. Here we
      show that Stab2 functions in a signal transduction pathway regulating arterial
      venous differentiation during zebrafish embryogenesis. Stab2 morpholino knockdown
      embryos (morphants) display an absence of intersegmental vessels and defects in
      the axial vessel formation. In addition, Stab2 morphants show defects in arterial
      venous differentiation including the expansion of venous marker expression.
      Simultaneous knockdown of Stabilin-2 and Has2, an HA synthetase, results in a
      synergistic effect, arguing that HA and Stab2 interact during vasculature
      formation. Stab2 morphants display reduced Erk phosphorylation in the arterial
      progenitors, which is a known transducer of VEGF signaling, previously associated
      with arterial-venous differentiation. In addition, VEGF signaling acts as a
      negative feedback loop to repress stab2 expression. These results argue that
      Stab2 is involved in a novel signaling pathway that plays an important role in
      regulating Erk phosphorylation and establishing arterial-venous identity. 

PMID- 24586358
TI  - Towards a more nuanced view of vocal attractiveness.
AB  - This study reports on male and female Californians' ratings of vocal
      attractiveness for 30 male and 30 female voices reading isolated words. While
      ratings by both sexes were highly correlated, males generally rated fellow males
      as less attractive than females did, but both females and males had similar
      ratings of female voices. Detailed acoustic analyses of multiple parameters
      followed by principal component analyses on vowel and voice quality measures were
      conducted. Relevant principal components, along with additional independent
      acoustic measures, were entered into regression models to assess which acoustic
      properties predict attractiveness ratings. These models suggest that a
      constellation of acoustic features which indicate apparent talker size and
      conformity to community speech norms contribute to perceived vocal
      attractiveness. These results suggest that judgments of vocal attractiveness are
      more complex than previously described. 

PMID- 24586359
TI  - Treadmill workstations: the effects of walking while working on physical activity
      and work performance.
AB  - We conducted a 12-month-long experiment in a financial services company to study
      how the availability of treadmill workstations affects employees' physical
      activity and work performance. We enlisted sedentary volunteers, half of whom
      received treadmill workstations during the first two months of the study and the
      rest in the seventh month of the study. Participants could operate the treadmills
      at speeds of 0-2 mph and could use a standard chair-desk arrangement at will. (a)
      Weekly online performance surveys were administered to participants and their
      supervisors, as well as to all other sedentary employees and their supervisors.
      Using within-person statistical analyses, we find that overall work performance,
      quality and quantity of performance, and interactions with coworkers improved as
      a result of adoption of treadmill workstations. (b) Participants were outfitted
      with accelerometers at the start of the study. We find that daily total physical
      activity increased as a result of the adoption of treadmill workstations. 

PMID- 24586360
TI  - A multi-site validation in India of the line probe assay for the rapid diagnosis
      of multi-drug resistant tuberculosis directly from sputum specimens.
AB  - Rifampicin (R) and isoniazid (H) are key first-line anti-tuberculosis drugs.
      Failure to detect resistance to these two drugs early results in treatment
      failure and poor clinical outcomes. The study purpose was to validate the use of
      the GenoType MTBDRplus line probe assay (LPA) to detect resistance to R and H in
      Mycobacterium tuberculosis strains directly from smear-positive sputum samples in
      India. METHOD: Smear positive sputum specimens from 320 patients were subjected
      to LPA and results compared against those from conventional Lowenstein Jensen
      (LJ) culture and drug susceptibility testing (C&DST). All specimens with
      discordant R DST results were subjected to either sequencing of the rpoB gene
      and/or repeat DST on liquid culture (MGIT 960) at a National Reference
      Laboratory. RESULTS: Significantly higher proportion of interpretable results
      were observed with LPA compared to LJ C&DST (94% vs. 80%, p-value <0.01). A total
      of 248 patients had both LJ and LPA DST results available; 232 (93.5%) had
      concordant R DST results. Among the 16 discordant R DST results, 13 (81%) were
      resolved in agreement with LPA results. Final LPA performance characteristics
      were sensitivity 96% (CI: 90%-98%), specificity 99% (CI: 95%-99%), positive
      predictive value 99% (CI: 95%-99%), and negative predictive value 95% (CI: 89%
      98%). The median turnaround testing time, including specimen transportation time,
      on LPA was 11 days as compared with 89 days for LJ C&DST. CONCLUSIONS: LPA proved
      highly accurate in the rapid detection of R resistance. The reduction in time to
      diagnosis may potentially enable earlier commencement of the appropriate drug
      therapy, leading to some reduction of transmission of drug-resistant strains.

PMID- 24586361
TI  - Deficient phosphorylation of Stat1 in leukocytes identifies neutralizing
      antibodies in multiple sclerosis patients treated with interferon-beta.
AB  - BACKGROUND: Anti interferon-beta (IFN-beta) neutralizing antibodies (NAb) affect
      efficacy of treatment of multiple sclerosis patients, but exactly when the
      detrimental effects of NAbs offset therapeutic efficacy is debated.
      Quantification of intracellular pathway-specific phosphorylation by phospho
      specific flow cytometry (phosphoflow) is a promising tool for evaluation of these
      effects in primary immune cells from treated patients at the single-cell level.
      METHOD: Samples for phosphoflow and gene expression changes were collected before
      administration of IFN-beta and at four, six, and eight hours thereafter. Patients
      were NAb negative (n = 3) or were NAb positive with low/medium (n = 1) or high (n
      = 2) NAb titers. Levels of phosphorylation of six Stat transcription factors
      (pStat) in seven cell subtypes and expression levels of 71 pathway-specific genes
      in whole blood were measured. The data was subjected to principal component
      analysis (PCA), fifty-fifty MANOVA, ANOVA, and partial least square regression
      (PLSR). RESULTS: PCA of pStat levels clustered patients according to NAb class
      independently of time. PCA of gene expression data clustered patients according
      to NAb class but was affected by time and treatment. In the fifty-fifty MANOVA,
      NAb class was significant for both pStat levels and gene expression data. The
      ANOVA identified pStat1 protein in several cell subtypes as significantly
      affected by NAb class. The best fitting model for NAb prediction based on PLSR
      included pStat1 in monocytes, T cells, or lymphocytes and pStat3 in monocytes (r
      = 0.97). Gene expression data were slightly less predictive of NAb titers.
      CONCLUSION: Based on this proof of concept study, we hypothesize that NAb effects
      can be monitored by evaluation of a single biomarker, pStat1, in either monocytes
      or T cells by phosphoflow directly after IFN-beta administration. The method will
      significantly reduce cost relative to labor intensive in vitro methods and offers
      a patient-specific approach to NAb evaluation.

PMID- 24586362
TI  - Projected distributions and diversity of flightless ground beetles within the
      Australian Wet Tropics and their environmental correlates.
AB  - With the impending threat of climate change, greater understanding of patterns of
      species distributions and richness and the environmental factors driving them are
      required for effective conservation efforts. Species distribution models enable
      us to not only estimate geographic extents of species and subsequent patterns of
      species richness, but also generate hypotheses regarding environmental factors
      determining these spatial patterns. Projected changes in climate can then be used
      to predict future patterns of species distributions and richness. We created
      distribution models for most of the flightless ground beetles (Carabidae) within
      the Wet Tropics World Heritage Area of Australia, a major component of regionally
      endemic invertebrates. Forty-three species were modelled and the environmental
      correlates of these distributions and resultant patterns of species richness were
      examined. Flightless ground beetles generally inhabit upland areas characterised
      by stable, cool and wet environmental conditions. These distribution and richness
      patterns are best explained using the time-stability hypothesis as this group's
      primary habitat, upland rainforest, is considered to be the most stable regional
      habitat. Projected changes in distributions indicate that as upward shifts in
      distributions occur, species currently confined to lower and drier mountain
      ranges will be more vulnerable to climate change impacts than those restricted to
      the highest and wettest mountains. Distribution models under projected future
      climate change suggest that there will be reductions in range size, population
      size and species richness under all emission scenarios. Eighty-eight per cent of
      species modelled are predicted to decline in population size by over 80%, for the
      most severe emission scenario by the year 2080. These results suggest that
      flightless ground beetles are among the most vulnerable taxa to climate change
      impacts so far investigated in the Wet Tropics World Heritage Area. These
      findings have dramatic implications for all other flightless insect taxa and the
      future biodiversity of this region. 

PMID- 24586363
TI  - The changing epidemiology of human African trypanosomiasis among patients from
      nonendemic countries--1902-2012.
AB  - BACKGROUND: Although human African trypanosomiasis (HAT) is uncommon among
      patients from non-endemic countries (NEC), there has been an increase in the
      number of cases reported in recent years. METHODS: A systematic review of the
      literature was performed. The number of incoming tourists to HAT endemic
      countries was obtained from the United Nations World Tourism Organization. All
      HAT cases diagnosed in patients from NEC were included. Immigrants and refugees
      were excluded. We compared patients during and after the colonial period, and
      analyzed the relationship between the number of incoming travellers and the
      number of HAT cases. RESULTS: Between 1902 and 2012, HAT was reported in 244
      patients. Most HAT cases were reported before 1920, and after the year 2000. In
      the colonial era the average age of patients was lower (32.5+/-7.8 vs. 43.0+/
      16.1 years, P<0.001), the proportion of females was lower (10.0% vs. 23.9%,
      P<0.01], most cases were diagnosed in expatriates, missionaries and soldiers
      (74.3%), and Gambian trypanosomiasis accounted for 86/110, (78%) of cases. In the
      post-colonial era most patients 91/125 (72.8%) were short-term tourists to game
      parks in Eastern and South-Eastern Africa (mainly in Tanzania); Rhodesian
      trypanosomiasis accounted for 94/123 (76.4%) of cases. Between 1995 and 2010
      there has been a constant linear increase in the number of incoming tourists to
      Tanzania, and HAT cases occurred in small outbreaks rather than following a
      similar linear pattern. CONCLUSIONS: In recent decades HAT patients from NEC are
      older, and more likely to be tourists who acquired the disease while visiting
      game-parks in Eastern and South-Eastern Africa. While Rhodesian trypanosomiasis
      is relatively uncommon among Africans, it now accounts for most cases reported
      among patients from NEC. Returning febrile travellers without an alternative
      diagnosis should be evaluated for HAT. Cases among travellers may serve as
      sentinels for Rhodesian trypanosomiasis "hot spots" in Africa.

PMID- 24586364
TI  - Spontaneous, pro-arrhythmic calcium signals disrupt electrical pacing in mouse
      pulmonary vein sleeve cells.
AB  - The pulmonary vein, which returns oxygenated blood to the left atrium, is
      ensheathed by a population of unique, myocyte-like cells called pulmonary vein
      sleeve cells (PVCs). These cells autonomously generate action potentials that
      propagate into the left atrial chamber and cause arrhythmias resulting in atrial
      fibrillation; the most common, often sustained, form of cardiac arrhythmia. In
      mice, PVCs extend along the pulmonary vein into the lungs, and are accessible in
      a lung slice preparation. We exploited this model to study how aberrant Ca(2+)
      signaling alters the ability of PVC networks to follow electrical pacing.
      Cellular responses were investigated using real-time 2-photon imaging of lung
      slices loaded with a Ca(2+)-sensitive fluorescent indicator (Ca(2+) measurements)
      and phase contrast microscopy (contraction measurements). PVCs displayed global
      Ca(2+) signals and coordinated contraction in response to electrical field
      stimulation (EFS). The effects of EFS relied on both Ca(2+) influx and Ca(2+)
      release, and could be inhibited by nifedipine, ryanodine or caffeine. Moreover,
      PVCs had a high propensity to show spontaneous Ca(2+) signals that arose via
      stochastic activation of ryanodine receptors (RyRs). The ability of electrical
      pacing to entrain Ca(2+) signals and contractile responses was dramatically
      influenced by inherent spontaneous Ca(2+) activity. In PVCs with relatively low
      spontaneous Ca(2+) activity (<1 Hz), entrainment with electrical pacing was good.
      However, in PVCs with higher frequencies of spontaneous Ca(2+) activity (>1.5
      Hz), electrical pacing was less effective; PVCs became unpaced, only partially
      paced or displayed alternans. Because spontaneous Ca(2+) activity varied between
      cells, neighboring PVCs often had different responses to electrical pacing. Our
      data indicate that the ability of PVCs to respond to electrical stimulation
      depends on their intrinsic Ca(2+) cycling properties. Heterogeneous spontaneous
      Ca(2+) activity arising from stochastic RyR opening can disengage them from sinus
      rhythm and lead to autonomous, pro-arrhythmic activity. 

PMID- 24586365
TI  - Novel protocol for persister cells isolation.
AB  - Bacterial persistence, where a fraction of a population presents a transient
      resistance to bactericidal substances, has great medical importance due to its
      relation with the appearance of antibiotic resistances and untreatable bacterial
      chronic infections. The mechanisms behind this phenomenon remain largely unknown
      in spite of recent advances, in great part because of the difficulty in isolating
      the very small fraction of the population that is in this state at any given
      time. Current protocols for persister isolation have resulted in possible biases
      because of the induction of this state by the protocol itself. Here we present a
      novel protocol that allows rapid isolation of persister cells both from
      exponential and stationary phase. Moreover, it is capable of differentiating
      between type I and type II persister cells, which should allow the field to move
      beyond its current state of studying only one type. While this protocol prompts a
      revision of many of the current results, it should greatly facilitate further
      advances in the field. 

PMID- 24586366
TI  - Neural substrates of interactive musical improvisation: an FMRI study of 'trading
      fours' in jazz.
AB  - Interactive generative musical performance provides a suitable model for
      communication because, like natural linguistic discourse, it involves an exchange
      of ideas that is unpredictable, collaborative, and emergent. Here we show that
      interactive improvisation between two musicians is characterized by activation of
      perisylvian language areas linked to processing of syntactic elements in music,
      including inferior frontal gyrus and posterior superior temporal gyrus, and
      deactivation of angular gyrus and supramarginal gyrus, brain structures directly
      implicated in semantic processing of language. These findings support the
      hypothesis that musical discourse engages language areas of the brain specialized
      for processing of syntax but in a manner that is not contingent upon semantic
      processing. Therefore, we argue that neural regions for syntactic processing are
      not domain-specific for language but instead may be domain-general for
      communication. 

PMID- 24586367
TI  - Generalization of clustering coefficients to signed correlation networks.
AB  - The recent interest in network analysis applications in personality psychology
      and psychopathology has put forward new methodological challenges. Personality
      and psychopathology networks are typically based on correlation matrices and
      therefore include both positive and negative edge signs. However, some
      applications of network analysis disregard negative edges, such as computing
      clustering coefficients. In this contribution, we illustrate the importance of
      the distinction between positive and negative edges in networks based on
      correlation matrices. The clustering coefficient is generalized to signed
      correlation networks: three new indices are introduced that take edge signs into
      account, each derived from an existing and widely used formula. The performances
      of the new indices are illustrated and compared with the performances of the
      unsigned indices, both on a signed simulated network and on a signed network
      based on actual personality psychology data. The results show that the new
      indices are more resistant to sample variations in correlation networks and
      therefore have higher convergence compared with the unsigned indices both in
      simulated networks and with real data. 

PMID- 24586368
TI  - People with easier to pronounce names promote truthiness of claims.
AB  - When people make judgments about the truth of a claim, related but nonprobative
      information rapidly leads them to believe the claim--an effect called
      "truthiness". Would the pronounceability of others' names also influence the
      truthiness of claims attributed to them? We replicated previous work by asking
      subjects to evaluate people's names on a positive dimension, and extended that
      work by asking subjects to rate those names on negative dimensions. Then we
      addressed a novel theoretical issue by asking subjects to read that same list of
      names, and judge the truth of claims attributed to them. Across all experiments,
      easily pronounced names trumped difficult names. Moreover, the effect of
      pronounceability produced truthiness for claims attributed to those names. Our
      findings are a new instantiation of truthiness, and extend research on the truth
      effect as well as persuasion by showing that subjective, tangential properties
      such as ease of processing can matter when people evaluate information attributed
      to a source.

PMID- 24586369
TI  - The trehalose phosphotransferase system (PTS) in E. coli W can transport low
      levels of sucrose that are sufficient to facilitate induction of the csc sucrose
      catabolism operon.
AB  - Plasticity in substrate acceptance is a well-characterised phenomenon for
      disaccharide transporters. Sucrose, a non-reducing disaccharide, is usually
      metabolised via either the permease-mediated chromosomally-encoded sucrose
      catabolism (csc) regulon or the sucrose phosphotransferase system (PTS). E. coli
      W is a fast-growing strain which efficiently utilises sucrose at concentrations
      above 1% via the csc regulon. To examine if sucrose could be metabolised via
      other routes, a library of transposon mutants was generated and screened on 0.2%
      sucrose. One mutant identified from this library had an insertion in the
      repressor for the regulon controlling catabolism of the disaccharide trehalose
      (treR). A series of mutants was constructed to elucidate the mechanism of sucrose
      utilization in the treR insertion strain. Analysis of these mutants provided
      evidence that deletion of TreR enables uptake of sucrose via TreB, an enzyme II
      protein required for PTS-mediated uptake of trehalose. Once inside the cell, this
      sucrose is not processed by the TreC hydrolase, nor is it sufficient for growth
      of the strain. QRT-PCR analysis showed that levels of cscA (invertase) transcript
      increased in the WDeltatreR mutant relative to the wild-type strain when grown
      under low sucrose conditions. This result suggests that the intracellular sucrose
      provided by TreB can facilitate de-repression of the csc regulon, leading to
      increased gene expression, sucrose uptake and sucrose utilization in the treR
      mutant. 

PMID- 24586370
TI  - Changes in topological organization of functional PET brain network with normal
      aging.
AB  - Recent studies about brain network have suggested that normal aging is associated
      with alterations in coordinated patterns of the large-scale brain functional and
      structural systems. However, age-related changes in functional networks
      constructed via positron emission tomography (PET) data are still barely
      understood. Here, we constructed functional brain networks composed of 90 regions
      in younger (mean age 36.5 years) and older (mean age 56.3 years) age groups with
      PET data. 113 younger and 110 older healthy individuals were separately selected
      for two age groups, from a physical examination database. Corresponding brain
      functional networks of the two groups were constructed by thresholding average
      cerebral glucose metabolism correlation matrices of 90 regions and analysed using
      graph theoretical approaches. Although both groups showed normal small-world
      architecture in the PET networks, increased clustering and decreased efficiency
      were found in older subjects, implying a degeneration process that brain system
      shifts from a small-world network to regular one along with normal aging.
      Moreover, normal senescence was related to changed nodal centralities
      predominantly in association and paralimbic cortex regions, e.g. increasing in
      orbitofrontal cortex (middle) and decreasing in left hippocampus. Additionally,
      the older networks were about equally as robust to random failures as younger
      counterpart, but more vulnerable against targeted attacks. Finally, methods in
      the construction of the PET networks revealed reasonable robustness. Our findings
      enhanced the understanding about the topological principles of PET networks and
      changes related to normal aging.

PMID- 24586371
TI  - Molecular phylogeny of the genus Lolliguncula steenstrup, 1881 based on nuclear
      and mitochondrial DNA sequences indicates genetic isolation of populations from
      north and South atlantic, and the possible presence of further cryptic species.
AB  - Squid of the genus Lolliguncula Steenstrup, 1881 are small bodied, coastal
      species capable of tolerating low salinity. Lolliguncula sp. are found
      exclusively in the New World, although only one of the four recognized species
      (Lolliguncula brevis) occurs in the Atlantic Ocean. Preliminary morphological
      analyses suggest that Lolliguncula brevis populations in the North and South
      Atlantic may represent distinct species. The principal objective of the present
      study was to verify the phylogenetic relationships within the genus and test for
      the presence of possible cryptic species. Both gene and species tree topologies
      indicated that Lolliguncula brevis specimens from the North and South Atlantic
      represent distinct phylogenetic clades. In contrast with previous studies, L.
      panamensis was identified as the basal species of the genus. Our results provide
      important insights into the phylogenetic relationships among the Lolliguncula
      specimens analyzed, and confirm the genetic separation of Lolliguncula brevis
      populations of the North and South Atlantic at the level of sister species. 

PMID- 24586372
TI  - Extending employment beyond the pensionable age: a cohort study of the influence
      of chronic diseases, health risk factors, and working conditions.
AB  - BACKGROUND: In response to the economic consequences of ageing of the population,
      governments are seeking ways with which people might work into older age. We
      examined the association of working conditions and health with extended
      employment (defined as >6 months beyond the pensionable age) in a cohort of
      older, non-disabled employees who have reached old-age retirement. METHODS: A
      total of 4,677 Finnish employees who reached their old-age pensionable date
      between 2005 and 2011 (mean age 59.8 years in 2005, 73% women) had their survey
      responses before pensionable age linked to national health and pension registers,
      resulting in a prospective cohort study. RESULTS: In all, 832 participants
      (17.8%) extended their employment by more than 6 months beyond the pensionable
      date. After multivariable adjustment, the following factors were associated with
      extended employment: absence of diagnosed mental disorder (OR 1.25, 95%
      confidence interval = 1.01-1.54) and psychological distress (OR 1.68; 1.35-2.08)
      and of the work characteristics, high work time control (OR 2.31; 1.88-2.84). The
      projected probability of extended employment was 21.3% (19.5-23.1) among those
      free of psychiatric morbidity and with high work time control, while the
      corresponding probability was only 9.2% (7.4-11.4) among those with both
      psychiatric morbidity and poor work time control. The contribution of chronic
      somatic diseases was modest. CONCLUSIONS: In the present study, good mental
      health in combination with the opportunity to control work time seem to be key
      factors in extended employment into older age. In addition, high work time
      control might promote work life participation irrespective of employees' somatic
      disease status.

PMID- 24586373
TI  - Age-dependent male mating investment in Drosophila pseudoobscura.
AB  - Male mating investment can strongly influence fitness gained from a mating. Yet,
      male mating investment often changes with age. Life history theory predicts that
      mating investment should increase with age, and males should become less
      discriminatory about their mate as they age. Understanding age-dependent changes
      in male behavior and their effects on fitness is important for understanding how
      selection acts in age-structured populations. Although the independent effects of
      male or female age have been studied in many species, how these interact to
      influence male mating investment and fitness is less well understood. We mated
      Drosophila pseudoobscura males of five different age classes (4-, 8-, 11-, 15-,
      19-day old) to either young (4-day) or old (11-day) females, and measured
      copulation duration and early post-mating fecundity. Along with their independent
      effects, we found a strong interaction between the effects of male and female
      ages on male mating investment and fitness from individual matings. Male mating
      investment increased with male age, but this increase was more prominent in
      matings with young females. Male D. pseudoobscura made smaller investments when
      mating with old females. The level of such discrimination based on female age,
      however, also changed with male age. Intermediate aged males were most
      discriminatory, while the youngest and the oldest males did not discriminate
      between females of different ages. We also found that larger male mating
      investments resulted in higher fitness payoffs. Our results show that male and
      female ages interact to form a complex pattern of age-specific male mating
      investment and fitness. 

PMID- 24586374
TI  - Migration patterns of subgenus Alnus in Europe since the last glacial maximum: a
      systematic review.
AB  - BACKGROUND/AIMS: Recently, new palaeoecological records supported by molecular
      analyses and palaeodistributional modelling have provided more comprehensive
      insights into plant behaviour during the last Quaternary cycle. We reviewed the
      migration history of species of subgenus Alnus during the last 50,000 years in
      Europe with a focus on (1) a general revision of Alnus history since the Last
      Glacial Maximum (LGM), (2) evidence of northern refugia of Alnus populations
      during the LGM and (3) the specific history of Alnus in particular European
      regions. METHODOLOGY: We determined changes in Alnus distribution on the basis of
      811 and 68 radiocarbon-dated pollen and macrofossil sites, respectively. We
      compiled data from the European Pollen Database, the Czech Quaternary
      Palynological Database, the Eurasian Macrofossil Database and additional
      literature. Pollen percentage thresholds indicating expansions or retreats were
      used to describe patterns of past Alnus occurrence. PRINCIPAL FINDINGS: An
      expansion of Alnus during the Late Glacial and early Holocene periods supports
      the presence of alders during the LGM in southern peninsulas and northerly areas
      in western Europe, the foothills of the Alps, the Carpathians and northeastern
      Europe. After glaciers withdrew, the ice-free area of Europe was likely colonized
      from several regional refugia; the deglaciated area of Scandinavia was likely
      colonized from a single refugium in northeastern Europe. In the more northerly
      parts of Europe, we found a scale-dependent pattern of Alnus expansion
      characterised by a synchronous increase of Alnus within individual regions,
      though with regional differences in the times of the expansion. In southern
      peninsulas, the Alps and the Carpathians, by contrast, it seems that Alnus
      expanded differently at individual sites rather than synchronously in whole
      regions. CONCLUSIONS: Our synthesis supports the idea that northern LGM
      populations were important sources of postglacial Alnus expansion. The delayed
      Alnus expansion apparent in some regions was likely a result of environmental
      limitations.

PMID- 24586375
TI  - DNA aptamers against exon v10 of CD44 inhibit breast cancer cell migration.
AB  - CD44 adhesion molecules are expressed in many breast cancer cells and have been
      demonstrated to play a key role in regulating malignant phenotypes such as
      growth, migration, and invasion. CD44 is an integral transmembrane protein
      encoded by a single 20-exon gene. The diversity of the biological functions of
      CD44 is the result of the various splicing variants of these exons. Previous
      studies suggest that exon v10 of CD44 plays a key role in promoting cancer
      invasion and metastasis, however, the molecular mechanisms are not clear. Given
      the fact that exon v10 is in the ectodomain of CD44, we hypothesized that CD44
      forms a molecular complex with other cell surface molecules through exon v10 in
      order to promote migration of breast cancer cells. In order to test this
      hypothesis, we selected DNA aptamers that specifically bound to CD44 exon v10
      using Systematic Evolution of Ligands by Exponential Enrichment (SELEX). We
      selected aptamers that inhibited migration of breast cancer cells. Co
      immunoprecipitation studies demonstrated that EphA2 was co-precipitated with
      CD44. Pull-down studies demonstrated that recombinant CD44 exon v10 bound to
      EphA2 and more importantly aptamers that inhibited migration also prevented the
      binding of EphA2 to exon v10. These results suggest that CD44 forms a molecular
      complex with EphA2 on the breast cancer cell surface and this complex plays a key
      role in enhancing breast cancer migration. These results provide insight not only
      for characterizing mechanisms of breast cancer migration but also for developing
      target-specific therapy for breast cancers and possibly other cancer types
      expressing CD44 exon v10. 

PMID- 24586377
TI  - Surviving coral bleaching events: porites growth anomalies on the Great Barrier
      Reef.
AB  - Mass coral bleaching affected large parts of the Great Barrier Reef (GBR) in 1998
      and 2002. In this study, we assessed if signatures of these major thermal stress
      events were recorded in the growth characteristics of massive Porites colonies.
      In 2005 a suite of short (<50 cm) cores were collected from apparently healthy,
      surviving Porites colonies, from reefs in the central GBR (18-19 degrees S) that
      have documented observations of widespread bleaching. Sites included inshore
      (Nelly Bay, Pandora Reef), annually affected by freshwater flood events, midshelf
      (Rib Reef), only occasionally affected by freshwater floods and offshore
      (Myrmidon Reef) locations primarily exposed to open ocean conditions. Annual
      growth characteristics (extension, density and calcification) were measured in
      144 cores from 79 coral colonies and analysed over the common 24-year period,
      1980-2003. Visual examination of the annual density bands revealed growth
      hiatuses associated with the bleaching years in the form of abrupt decreases in
      annual linear extension rates, high density stress bands and partial mortality.
      The 1998 mass-bleaching event reduced Porites calcification by 13 and 18% on the
      two inshore locations for 4 years, followed by recovery to baseline calcification
      rates in 2002. Evidence of partial mortality was apparent in 10% of the offshore
      colonies in 2002; however no significant effects of the bleaching events were
      evident in the calcification rates at the mid shelf and offshore sites. These
      results highlight the spatial variation of mass bleaching events and that all
      reef locations within the GBR were not equally stressed by the 1998 and 2002 mass
      bleaching events, as some models tend to suggest, which enabled recovery of
      calcification on the GBR within 4 years. The dynamics in annual calcification
      rates and recovery displayed here should be used to improve model outputs that
      project how coral calcification will respond to ongoing warming of the tropical
      oceans. 

PMID- 24586376
TI  - Comprehensive analysis of HPV16 integration in OSCC reveals no significant impact
      of physical status on viral oncogene and virally disrupted human gene expression.
AB  - Infection with high-risk human papillomavirus (HPV) type 16 is an independent
      risk factor for the development of oropharyngeal squamous cell carcinomas (OSCC).
      However, it is unclear whether viral integration is an essential hallmark in the
      carcinogenic process of OSCC and whether HPV integration correlates with the
      level of viral gene transcription and influences the expression of disrupted host
      genes. We analyzed 75 patients with OSCC. HPV16-positivity was proven by
      p16(INK4A) immunohistochemistry, PCR and FISH. Viral integration was examined
      using DIPS- as well as APOT-PCR. Viral E2, E6 and E7 gene expression levels were
      quantified by quantitative reverse transcriptase (RT-q)PCR. Expression levels of
      7 human genes disrupted by the virus were extracted from mRNA expression
      profiling data of 32 OSCCs. Viral copy numbers were assessed by qPCR in 73
      tumors. We identified 37 HPV16-human fusion products indicating viral integration
      in 29 (39%) OSCC. In the remaining tumors (61%) only episome-derived PCR products
      were detected. When comparing OSCC with or without an integration-derived fusion
      product, we did not find significant differences in the mean RNA expression of
      viral genes E2, E6 and E7 or the viral copy numbers per cell, nor did the RNA
      expression of the HPV-disrupted genes differ from either group of OSCC. In
      conclusion, our data do not support the hypothesis that integration affects the
      levels of viral and/or HPV-disrupted human gene transcripts. Thus constitutive,
      rather than a high level, of expression of oncogene transcripts appears to be
      required in HPV-related OSCC. 

PMID- 24586378
TI  - Benzimidazoisoquinolines: a new class of rapidly metabolized aryl hydrocarbon
      receptor (AhR) ligands that induce AhR-dependent Tregs and prevent murine graft
      versus-host disease.
AB  - The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor
      that plays multiple roles in regulation of immune and inflammatory responses. The
      ability of certain AhR ligands to induce regulatory T cells (Tregs) has generated
      interest in developing AhR ligands for therapeutic treatment of immune-mediated
      diseases. To this end, we designed a screen for novel Treg-inducing compounds
      based on our understanding of the mechanisms of Treg induction by the well
      characterized immunosuppressive AhR ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin
      (TCDD). We screened a ChemBridge small molecule library and identified 10-chloro
      7H-benzimidazo[2,1-a]benzo[de]Iso-quinolin-7-one (10-Cl-BBQ) as a potent AhR
      ligand that was rapidly metabolized and not cytotoxic to proliferating T cells.
      Like TCDD,10-Cl-BBQ altered donor CD4(+) T cell differentiation during the early
      stages of a graft versus host (GVH) response resulting in expression of high
      levels of CD25, CTLA-4 and ICOS, as well as several genes associated with Treg
      function. The Treg phenotype required AhR expression in the donor CD4(+) T cells.
      Foxp3 was not expressed in the AhR-induced Tregs implicating AhR as an
      independent transcription factor for Treg induction. Structure-activity studies
      showed that unsubstituted BBQ as well as 4, 11-dichloro-BBQ were capable of
      inducing AhR-Tregs. Other substitutions reduced activation of AhR. Daily
      treatment with 10-Cl-BBQ during the GVH response prevented development of GVH
      disease in an AhR-dependent manner with no overt toxicity. Together, our data
      provide strong support for development of select BBQs that activate the AhR to
      induce Tregs for treatment of immune-mediated diseases. 

PMID- 24586379
TI  - Influence of shape on the haptic size aftereffect.
AB  - Recently, we showed a strong haptic size aftereffect by means of a size bisection
      task: after adaptation to a large sphere, subsequently grasped smaller test
      spheres felt even smaller, and vice versa. In the current study, we questioned
      whether the strength of this aftereffect depends on shape. In four experimental
      conditions, we determined the aftereffect after adaptation to spheres and
      tetrahedra and subsequent testing also with spheres and tetrahedra. The results
      showed a clear influence of shape: the haptic aftereffect was much stronger if
      adaptation and test stimuli were identical in shape than if their shapes were
      different. Therefore, it would be more appropriate to term such aftereffects
      haptic shape-size aftereffects, as size alone could not be the determining
      factor. This influence of shape suggests that higher cortical areas are involved
      in this aftereffect and that it cannot be due to adaptation of peripheral
      receptors. An additional finding is that the geometric property or combination of
      properties participants use in the haptic size bisection task varies widely over
      participants, although participants themselves are quite consistent.

PMID- 24586381
TI  - Comparative analysis of normalised difference spectral indices derived from MODIS
      for detecting surface water in flooded rice cropping systems.
AB  - Identifying managed flooding in paddy fields is commonly used in remote sensing
      to detect rice. Such flooding, followed by rapid vegetation growth, is a reliable
      indicator to discriminate rice. Spectral indices (SIs) are often used to perform
      this task. However, little work has been done on determining which spectral
      combination in the form of Normalised Difference Spectral Indices (NDSIs) is most
      appropriate for surface water detection or which thresholds are most robust to
      separate water from other surfaces in operational contexts. To address this, we
      conducted analyses on satellite and field spectral data from an agronomic
      experiment as well as on real farming situations with different soil and plant
      conditions. Firstly, we review and select NDSIs proposed in the literature,
      including a new combination of visible and shortwave infrared bands. Secondly, we
      analyse spectroradiometric field data and satellite data to evaluate mixed pixel
      effects. Thirdly, we analyse MODIS data and Landsat data at four sites in Europe
      and Asia to assess NDSI performance in real-world conditions. Finally, we test
      the performance of the NDSIs on MODIS temporal profiles in the four sites. We
      also compared the NDSIs against a combined index previously used for agronomic
      flood detection. Analyses suggest that NDSIs using MODIS bands 4 and 7, 1 and 7,
      4 and 6 or 1 and 6 perform best. A common threshold for each NDSI across all
      sites was more appropriate than locally adaptive thresholds. In general, NDSIs
      that use band 7 have a negligible increase in Commission Error over those that
      use band 6 but are more sensitive to water presence in mixed land cover
      conditions typical of moderate spatial resolution analyses. The best performing
      NDSI is comparable to the combined index but with less variability in performance
      across sites, suggesting a more succinct and robust flood detection method.

PMID- 24586380
TI  - Preservation of general intelligence following traumatic brain injury:
      contributions of the Met66 brain-derived neurotrophic factor.
AB  - Brain-derived neurotrophic factor (BDNF) promotes survival and synaptic
      plasticity in the human brain. The Val66Met polymorphism of the BDNF gene
      interferes with intracellular trafficking, packaging, and regulated secretion of
      this neurotrophin. The human prefrontal cortex (PFC) shows lifelong neuroplastic
      adaption implicating the Val66Met BDNF polymorphism in the recovery of higher
      order executive functions after traumatic brain injury (TBI). In this study, we
      examined the effect of this BDNF polymorphism on the preservation of general
      intelligence following TBI. We genotyped a sample of male Vietnam combat veterans
      (n = 156) consisting of a frontal lobe lesion group with focal penetrating head
      injuries for the Val66Met BDNF polymorphism. Val/Met did not differ from Val/Val
      genotypes in general cognitive ability before TBI. However, we found substantial
      average differences between these groups in general intelligence (~ half a
      standard deviation or 8 IQ points), verbal comprehension (6 IQ points),
      perceptual organization (6 IQ points), working memory (8 IQ points), and
      processing speed (8 IQ points) after TBI. These results support the conclusion
      that Val/Met genotypes preserve general cognitive functioning, whereas Val/Val
      genotypes are largely susceptible to TBI. 

PMID- 24586382
TI  - The alarmin concept applied to human renal transplantation: evidence for a
      differential implication of HMGB1 and IL-33.
AB  - The endogenous molecules high mobility group box 1 (HMGB1) and interleukin-33 (IL
      33) have been identified as alarmins, capable of mediating danger signals during
      tissue damage. Here, we address their possible role as innate-immune mediators in
      ischemia-reperfusion injury (IRI) following human kidney transplantation. We
      analysed serum and urinary HMGB1 and IL-33 levels, all determined by enzyme
      linked immunosorbent assay, in a cohort of 26 deceased renal transplant
      recipients. Urinary HMGB1 and IL-33 levels were significantly increased as soon
      as 30 min after reperfusion, as compared to those before treatment. Moreover,
      both serum and urinary IL-33 (but not HMGB1) increase was positively correlated
      with cold ischemia time, from 30 min to 3 days post-transplantation. In vitro,
      human umbilical vein endothelial cells subjected to hypoxia conditions released
      both HMGB-1 and IL-33, while only the latter was further increased upon
      subsequent re-oxygenation. Finally, we postulate that leukocytes from renal
      recipient patients are targeted by both HMGB1 and IL-33, as suggested by
      increased transcription of their respective receptors (TLR2/4 and ST2L) shortly
      after transplantation. Consistent with this view, we found that iNKT cells, an
      innate-like T cell subset involved in IRI and targeted by IL-33 but not by HMGB1
      was activated 1 hour post-transplantation. Altogether, these results are in
      keeping with a potential role of IL-33 as an innate-immune mediator during kidney
      IRI in humans. 

PMID- 24586384
TI  - Association of serum periostin with cardiac function and short-term prognosis in
      acute myocardial infarction patients.
AB  - BACKGROUND: Periostin was proved to play an important role in extra-cellular
      matrix remodeling after acute myocardial infarction (AMI). Myocardial periostin
      was markedly up-regulated after AMI and participated in the maladaptive process
      of cardiac remodeling. However, few researches focused on the circulating
      periostin and its significance. This study aims to investigate the association of
      serum periostin level with cardiac function and short-term prognosis in AMI
      patients. METHODOLOGY/PRINCIPAL FINDINGS: We totally recruited 50 patients
      diagnosed as ST-elevation myocardial infarction. Blood samples were taken within
      12 hours after the onset of AMI before emergency coronary revascularization
      procedures. Serum periostin was measured using enzyme-linked immunosorbent assay.
      All patients received echocardiography examination within one week after
      hospitalization. Correlations of serum periostin with echocardiography
      parameters, Killip class and myocardium injury biomarkers (CK-MB/troponin T) were
      investigated. AMI patients were divided into two groups by serum periostin level
      (higher/lower periostin group) and followed up for six months. Primary endpoints
      included cardiovascular mortality, nonfatal stroke/transient ischemic attack,
      chest pain occurrence and re-hospitalization. Secondary endpoint referred to
      composite cardiovascular events including all the primary endpoints. RESULT:
      Serum periostin was in negative association with left ventricular ejection
      fraction (LVEF) (r =  -0.472, *p<0.01) and left atrium diameter (LAD) (r =  
      0.328, *p<0.05). Positive correlation was found between serum periostin level and
      Killip class (r = 0.395, *p<0.01). There was no association between serum
      periostin and CK-MB or troponin T (p>0.05). After six months follow up, patients
      in higher periostin group showed increased composite cardiovascular events
      (*p<0.05). Patients showed no significant difference in primary endpoints between
      the two groups. CONCLUSIONS/SIGNIFICANCE: Serum periostin was in negative
      correlation with LVEF and LAD, in positive association with Killip class and
      higher serum periostin level may be predictive for worse short-term disease
      prognosis indicated as more composite cardiovascular events six months post AMI.

PMID- 24586383
TI  - Quantitative analysis of the anti-proliferative activity of combinations of
      selected iron-chelating agents and clinically used anti-neoplastic drugs.
AB  - Recent studies have demonstrated that several chelators possess marked potential
      as potent anti-neoplastic drugs and as agents that can ameliorate some of the
      adverse effects associated with standard chemotherapy. Anti-cancer treatment
      employs combinations of several drugs that have different mechanisms of action.
      However, data regarding the potential interactions between iron chelators and
      established chemotherapeutics are lacking. Using estrogen receptor-positive MCF-7
      breast cancer cells, we explored the combined anti-proliferative potential of
      four iron chelators, namely: desferrioxamine (DFO), salicylaldehyde isonicotinoyl
      hydrazone (SIH), (E)-N'-[1-(2-hydroxy-5-nitrophenyl)ethyliden] isonicotinoyl
      hydrazone (NHAPI), and di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone
      (Dp44mT), plus six selected anti-neoplastic drugs. These six agents are used for
      breast cancer treatment and include: paclitaxel, 5-fluorouracil, doxorubicin,
      methotrexate, tamoxifen and 4-hydroperoxycyclophosphamide (an active metabolite
      of cyclophosphamide). Our quantitative chelator-drug analyses were designed
      according to the Chou-Talalay method for drug combination assessment. All
      combinations of these agents yielded concentration-dependent, anti-proliferative
      effects. The hydrophilic siderophore, DFO, imposed antagonism when used in
      combination with all six anti-tumor agents and this antagonistic effect increased
      with increasing dose. Conversely, synergistic interactions were observed with
      combinations of the lipophilic chelators, NHAPI or Dp44mT, with doxorubicin and
      also the combinations of SIH, NHAPI or Dp44mT with tamoxifen. The combination of
      Dp44mT with anti-neoplastic agents was further enhanced following formation of
      its redox-active iron and especially copper complexes. The most potent
      combinations of Dp44mT and NHAPI with tamoxifen were confirmed as synergistic
      using another estrogen receptor-expressing breast cancer cell line, T47D, but not
      estrogen receptor-negative MDA-MB-231 cells. Furthermore, the synergy of NHAPI
      and tamoxifen was confirmed using MCF-7 cells by electrical impedance data, a
      mitochondrial inner membrane potential assay and cell cycle analyses. This is the
      first systematic investigation to quantitatively assess interactions between Fe
      chelators and standard chemotherapies using breast cancer cells. These studies
      are vital for their future clinical development. 

PMID- 24586385
TI  - Comparative in vivo analysis of recombinant type II feline coronaviruses with
      truncated and completed ORF3 region.
AB  - Our previous in vitro comparative study on a feline coronavirus (FCoV) pair,
      differing only in the intactness of their ORF3abc regions, showed that the
      truncated ORF3abc plays an important role in the efficient macrophage/monocyte
      tropism of type II feline infectious peritonitis virus (FIPV). In the present
      study, we describe a challenge experiment with the same recombinant FCoVs in
      order to gain data on the in vivo characteristics on these viruses. While parent
      virus FIPV DF-2 developed feline infectious peritonitis in all the infected cats,
      its recombinant virus PBFIPV-DF-2, differing only in seven nucleotides, proved to
      be surprisingly low virulent, although caused an acute febrile episode similarly
      to the original FIPV DF-2. PBFIPV-DF-2 infection induced significantly lower
      virus neutralization titers than its parent virus, and lacked the second phase of
      viremia and development of fatal course of the disease. The recombinant PBFIPV-DF
      2-R3i with completed ORF3abc gained biological properties that differentiate
      between the feline enteric coronavirus (FECV) and FIPV biotypes such as intensive
      replication in the gut, absence of viremia and weak or no serological response.
      Using reverse genetic approaches our study is the first experimental proof that
      ORF3abc is indeed responsible for the restriction of FECV replication to the
      intestine in vivo. 

PMID- 24586386
TI  - Prospective screening of family members with moyamoya disease patients.
AB  - BACKGROUND: Genetic factors play an important role in the pathogenesis of
      moyamoya disease (MMD). Previous studies concentrated on familial MMD patients.
      In this study, we focused on family members of sporadic MMD patients, and aimed
      to gain a clearer understanding of the role that genetic factors play in MMD.
      METHODS: The immediate family members of MMD patients were initially screened by
      transcranial Doppler sonography (TCD) and positive cases were verified by
      magnetic resonance angiography (MRA). RESULTS: From July 2011 to March 2013,
      there were 527 MMD patients managed in our hospital, including 38 familial MMD
      cases. In this study, 285 immediate family members of 245 sporadic MMD patients
      were screened. Another 41 cases of familial MMD cases were identified, which
      included 21 family members and 20 corresponding sporadic MMD patients who had
      family members confirmed positive with MMD. As a result, the proportion of
      familial MMD patients increased from 7% (38/527) to 15% (79/527) in this period.
      For the main segments of the circle of Willis, Kappa values between TCD and MRA
      for the anterior cerebral arteries, middle cerebral arteries and posterior
      cerebral arteries were 0.91, 0.72, and 0.47, respectively. Familial cases
      confirmed by our screening showed a significantly higher percentage of
      asymptomatic patients (57%) compared with 9% from the control group who had a
      clear family history before. CONCLUSIONS: Familial MMD patients may account for a
      higher percentage among all cases than previously thought. Some family members of
      MMD patients may also have MMD, but not have any obvious symptoms. Routine
      screening should be implemented for all family members of MMD patients to improve
      the detection rate for this part of the patient base. TCD has a high diagnostic
      agreement with MRA for MMD. TCD may be the preferred choice for screening because
      it is inexpensive and safe.

PMID- 24586387
TI  - Vitamin D deficiency and exogenous vitamin D excess similarly increase diffuse
      atherosclerotic calcification in apolipoprotein E knockout mice.
AB  - BACKGROUND: Observational data associate lower levels of serum vitamin D with
      coronary artery calcification, cardiovascular events and mortality. However,
      there is little interventional evidence demonstrating that moderate vitamin D
      deficiency plays a causative role in cardiovascular disease. This study examined
      the cardiovascular effects of dietary vitamin D deficiency and of vitamin D
      receptor agonist (paricalcitol) administration in apolipoprotein E knockout mice.
      METHODS: Mice were fed atherogenic diets with normal vitamin D content (1.5
      IU/kg) or without vitamin D. Paricalcitol, or matched vehicle, was administered
      3* weekly by intraperitoneal injection. Following 20 weeks of these interventions
      cardiovascular phenotype was characterized by histological assessment of aortic
      sinus atheroma, soluble markers, blood pressure and echocardiography. To place
      the cardiovascular assessments in the context of intervention effects on bone,
      structural changes at the tibia were assessed by microtomography. RESULTS:
      Vitamin D deficient diet induced significant reductions in plasma vitamin D
      (p<0.001), trabecular bone volume (p<0.01) and bone mineral density (p<0.005).
      These changes were accompanied by an increase in calcification density (number of
      calcifications per mm(2)) of von Kossa-stained aortic sinus atheroma (461 versus
      200, p<0.01). Paricalcitol administration suppressed parathyroid hormone
      (p<0.001), elevated plasma calcium phosphate product (p<0.005) and induced an
      increase in calcification density (472 versus 200, p<0.005) similar to that seen
      with vitamin D deficiency. Atheroma burden, blood pressure, metabolic profile and
      measures of left ventricular hypertrophy were unaffected by the interventions.
      CONCLUSION: Vitamin D deficiency, as well as excess, increases atherosclerotic
      calcification. This phenotype is induced before other measures of cardiovascular
      pathology associated clinically with vitamin D deficiency. Thus, maintenance of
      an optimal range of vitamin D signalling may be important for prevention of
      atherosclerotic calcification.

PMID- 24586388
TI  - A cyclic nucleotide-gated channel mutation associated with canine daylight
      blindness provides insight into a role for the S2 segment tri-Asp motif in
      channel biogenesis.
AB  - Cone cyclic nucleotide-gated channels are tetramers formed by CNGA3 and CNGB3
      subunits; CNGA3 subunits function as homotetrameric channels but CNGB3 exhibits
      channel function only when co-expressed with CNGA3. An aspartatic acid (Asp) to
      asparagine (Asn) missense mutation at position 262 in the canine CNGB3 (D262N)
      subunit results in loss of cone function (daylight blindness), suggesting an
      important role for this aspartic acid residue in channel biogenesis and/or
      function. Asp 262 is located in a conserved region of the second transmembrane
      segment containing three Asp residues designated the Tri-Asp motif. This motif is
      conserved in all CNG channels. Here we examine mutations in canine CNGA3
      homomeric channels using a combination of experimental and computational
      approaches. Mutations of these conserved Asp residues result in the absence of
      nucleotide-activated currents in heterologous expression. A fluorescent tag on
      CNGA3 shows mislocalization of mutant channels. Co-expressing CNGB3 Tri-Asp
      mutants with wild type CNGA3 results in some functional channels, however, their
      electrophysiological characterization matches the properties of homomeric CNGA3
      channels. This failure to record heteromeric currents suggests that Asp/Asn
      mutations affect heteromeric subunit assembly. A homology model of S1-S6 of the
      CNGA3 channel was generated and relaxed in a membrane using molecular dynamics
      simulations. The model predicts that the Tri-Asp motif is involved in non
      specific salt bridge pairings with positive residues of S3/S4. We propose that
      the D262N mutation in dogs with CNGB3-day blindness results in the loss of these
      inter-helical interactions altering the electrostatic equilibrium within in the
      S1-S4 bundle. Because residues analogous to Tri-Asp in the voltage-gated Shaker
      potassium channel family were implicated in monomer folding, we hypothesize that
      destabilizing these electrostatic interactions impairs the monomer folding state
      in D262N mutant CNG channels during biogenesis. 

PMID- 24586390
TI  - Game-theoretic methods for functional response and optimal foraging behavior.
AB  - We develop a decision tree based game-theoretical approach for constructing
      functional responses in multi-prey/multi-patch environments and for finding the
      corresponding optimal foraging strategies. Decision trees provide a way to
      describe details of predator foraging behavior, based on the predator's sequence
      of choices at different decision points, that facilitates writing down the
      corresponding functional response. It is shown that the optimal foraging behavior
      that maximizes predator energy intake per unit time is a Nash equilibrium of the
      underlying optimal foraging game. We apply these game-theoretical methods to
      three scenarios: the classical diet choice model with two types of prey and
      sequential prey encounters, the diet choice model with simultaneous prey
      encounters, and a model in which the predator requires a positive recognition
      time to identify the type of prey encountered. For both diet choice models, it is
      shown that every Nash equilibrium yields optimal foraging behavior. Although
      suboptimal Nash equilibrium outcomes may exist when prey recognition time is
      included, only optimal foraging behavior is stable under evolutionary learning
      processes. 

PMID- 24586389
TI  - Stenotrophomonas maltophilia virulence and specific variations in trace elements
      during acute lung infection: implications in cystic fibrosis.
AB  - Metal ions are necessary for the proper functioning of the immune system, and,
      therefore, they might have a significant influence on the interaction between
      bacteria and host. Ionic dyshomeostasis has been recently observed also in cystic
      fibrosis (CF) patients, whose respiratory tract is frequently colonized by
      Stenotrophomonas maltophilia. For the first time, here we used an inductively
      mass spectrometry method to perform a spatial and temporal analysis of the
      pattern of changes in a broad range of major trace elements in response to
      pulmonary infection by S. maltophilia. To this, DBA/2 mouse lungs were
      comparatively infected by a CF strain and by an environmental one. Our results
      showed that pulmonary ionomic profile was significantly affected during
      infection. Infected mice showed increased lung levels of Mg, P, S, K, Zn, Se, and
      Rb. To the contrary, Mn, Fe, Co, and Cu levels resulted significantly decreased.
      Changes of element concentrations were correlated with pulmonary bacterial load
      and markers of inflammation, and occurred mostly on day 3 post-exposure, when
      severity of infection culminated. Interestingly, CF strain - significantly more
      virulent than the environmental one in our murine model - provoked a more
      significant impact in perturbing pulmonary metal homeostasis. Particularly,
      exposure to CF strain exclusively increased P and K levels, while decreased Fe
      and Mn ones. Overall, our data clearly indicate that S. maltophilia modulates
      pulmonary metal balance in a concerted and virulence-dependent manner
      highlighting the potential role of the element dyshomeostasis during the
      progression of S. maltophilia infection, probably exacerbating the harmful
      effects of the loss of CF transmembrane conductance regulator function. Further
      investigations are required to understand the biological significance of these
      alterations and to confirm they are specifically caused by S. maltophilia. 

PMID- 24586391
TI  - Tristetraprolin mediates anti-inflammatory effect of carbon monoxide against DSS
      induced colitis.
AB  - Endogenous carbon monoxide (CO) exerts anti-inflammatory effects. Tristetraprolin
      (TTP) is known to destabilize pro-inflammatory transcripts. Here we found that
      exogenous CO enhanced the decay of TNF-alpha mRNA and suppressed TNF-alpha
      expression in LPS-activated macrophages from wild-type (WT) mice. However, TTP
      deficiency abrogated the effects of exogenous CO. While CO treatment prior to DSS
      administration in WT mice significantly reduced inflammatory cytokine levels and
      colitis, it failed to reduce the pro-inflammatory cytokine levels and colitis in
      TTP knockout (KO) mice. Our results demonstrate that TTP is a key factor
      mediating the anti-inflammatory action of CO in DSS-induced colitis. 

PMID- 24586392
TI  - Facial expressions depicting compassionate and critical emotions: the development
      and validation of a new emotional face stimulus set.
AB  - Attachment with altruistic others requires the ability to appropriately process
      affiliative and kind facial cues. Yet there is no stimulus set available to
      investigate such processes. Here, we developed a stimulus set depicting
      compassionate and critical facial expressions, and validated its effectiveness
      using well-established visual-probe methodology. In Study 1, 62 participants
      rated photographs of actors displaying compassionate/kind and critical faces on
      strength of emotion type. This produced a new stimulus set based on N = 31
      actors, whose facial expressions were reliably distinguished as compassionate,
      critical and neutral. In Study 2, 70 participants completed a visual-probe task
      measuring attentional orientation to critical and compassionate/kind faces. This
      revealed that participants lower in self-criticism demonstrated enhanced
      attention to compassionate/kind faces whereas those higher in self-criticism
      showed no bias. To sum, the new stimulus set produced interpretable findings
      using visual-probe methodology and is the first to include higher order, complex
      positive affect displays. 

PMID- 24586393
TI  - Influence of land development on Holocene Porites coral calcification at Nagura
      Bay, Ishigaki Island, Japan.
AB  - To evaluate the relationships between coral calcification, thermal stress, and
      sedimentation and eutrophication linked to human impact (hereafter referred to as
      "land development") by river discharge, we analyzed growth characteristics in the
      context of a paleoenvironment that was reconstructed from geochemical signals in
      modern and fossil (1.2 cal kyr BP and 3.5 cal kyr BP, respectively) massive
      Porites corals from Nagura Bay ("Nagura") and from modern Porites corals from the
      estuary of the Todoroki River, Shiraho Reef ("Todoroki"). Both sites are on
      Ishigaki Island, Japan, and Nagura is located approximately 12 km west of
      Todoroki. At Nagura, the individual corals provide time windows of 13 (modern),
      10 (1.2 cal kyr BP), and 38 yr in length (3.5 cal kyr BP). Here, we present the
      coral annual calcification for Nagura and Todoroki, and (bi) monthly resolved
      records of Sr/Ca (a proxy of sea surface temperature (SST)) and Ba/Ca (a proxy of
      sedimentation and nutrients related to land development) for Nagura. At Nagura,
      the winter SST was cooler by 2.8 degrees C in the 1.2 cal kyr BP, and the annual
      and winter SSTs in the 3.5 cal kyr BP were cooler by 2.6 degrees C and 4.6
      degrees C, respectively. The annual periodicity of Ba/Ca in modern coral is
      linked to river discharge and is associated with land development including sugar
      cane cultivation. Modern coral calcification also has declined with SST warming
      and increasing Ba/Ca peaks in winter. However, calcification of fossil corals
      does not appear to have been influenced by variations in Sr/Ca and Ba/Ca. Modern
      coral growth characteristics at Nagura and Todoroki indicate that coral growth is
      both spatially and temporally influenced by river discharge and land development.
      At Nagura, our findings suggest that land development induces negative thermal
      sensitivity for calcification in winter due to sugar cane harvest, which is a
      specifically modern phenomenon. 

PMID- 24586394
TI  - Dynamic association of mortality hazard with body shape.
AB  - BACKGROUND: A Body Shape Index (ABSI) had been derived from a study of the United
      States National Health and Nutrition Examination Survey (NHANES) 1999-2004
      mortality data to quantify the risk associated with abdominal obesity (as
      indicated by a wide waist relative to height and body mass index). A national
      survey with longer follow-up, the British Health and Lifestyle Survey (HALS),
      provides another opportunity to assess the predictive power for mortality of
      ABSI. HALS also includes repeat observations, allowing estimation of the
      implications of changes in ABSI. METHODS AND FINDINGS: We evaluate ABSI z score
      relative to population normals as a predictor of all-cause mortality over 24
      years of follow-up to HALS. We found that ABSI is a strong indicator of mortality
      hazard in this population, with death rates increasing by a factor of 1.13 (95%
      confidence interval, 1.09-1.16) per standard deviation increase in ABSI and a
      hazard ratio of 1.61 (1.40-1.86) for those with ABSI in the top 20% of the
      population compared to those with ABSI in the bottom 20%. Using the NHANES
      normals to compute ABSI z scores gave similar results to using z scores derived
      specifically from the HALS sample. ABSI outperformed as a predictor of mortality
      hazard other measures of abdominal obesity such as waist circumference, waist to
      height ratio, and waist to hip ratio. Moreover, it was a consistent predictor of
      mortality hazard over at least 20 years of follow-up. Change in ABSI between two
      HALS examinations 7 years apart also predicted mortality hazard: individuals with
      a given initial ABSI who had rising ABSI were at greater risk than those with
      falling ABSI. CONCLUSIONS: ABSI is a readily computed dynamic indicator of health
      whose correlation with lifestyle and with other risk factors and health outcomes
      warrants further investigation.

PMID- 24586395
TI  - Aryl hydrocarbon receptor downregulates MYCN expression and promotes cell
      differentiation of neuroblastoma.
AB  - Neuroblastoma (NB) is the most common malignant disease of infancy. MYCN
      amplification is a prognostic factor for NB and is a sign of highly malignant
      disease and poor patient prognosis. In this study, we aimed to investigate novel
      MYCN-related genes and assess how they affect NB cell behavior. The different
      gene expression found in 10 MYCN amplification NB tumors and 10 tumors with
      normal MYCN copy number were analyzed using tissue oligonucleotide microarrays.
      Ingenuity Pathway Analysis was subsequently performed to identify the potential
      genes involved in MYCN regulation pathways. Aryl hydrocarbon receptor (AHR), a
      receptor for dioxin-like compounds, was found to be inversely correlated with
      MYCN expression in NB tissues. This correlation was confirmed in a further 14
      human NB samples. Moreover, AHR expression in NB tumors was found to correlate
      highly with histological grade of differentiation. In vitro studies revealed that
      AHR overexpression in NB cells induced spontaneous cell differentiation. In
      addition, it was found that ectopic expression of AHR suppressed MYCN promoter
      activity resulting in downregulation of MYCN expression. The suppression effect
      of AHR on the transcription of MYCN was compensated for by E2F1 overexpression,
      indicating that E2F1 is involved in the AHR-regulating MYCN pathway. Furthermore,
      AHR shRNA promotes the expression of E2F1 and MYCN in NB cells. These findings
      suggest that AHR is one of the upstream regulators of MYCN. Through the
      modulation of E2F1, AHR regulates MYCN gene expression, which may in turn affect
      NB differentiation. 

PMID- 24586396
TI  - Functional elastic hydrogel as recyclable membrane for the adsorption and
      degradation of methylene blue.
AB  - Developing the application of high-strength hydrogels has gained much attention
      in the fields of medical, pharmacy, and pollutant removal due to their
      versatility and stimulus-responsive properties. In this presentation, a high
      strength freestanding elastic hydrogel membrane was constructed by clay
      nanosheets, N, N-dimethylacrylamide and 2-acrylamide-2-methylpropanesulfonic acid
      for adsorption of methylene blue and heavy metal ions. The maximum values of
      elongation and Young's modulus for 0.5% AMPSNa hydrogel were 1901% and 949.4 kPa,
      respectively, much higher than those of traditional hydrogels. The adsorptions
      were confirmed to follow pseudo-second kinetic equation and Langmuir isotherm
      model fits the data well. The maximum adsorption capacity of hydrogel towards
      methylene blue was 434.8 mg g(-1). The hydrogel also exhibited higher separation
      selectivity to Pb(2+) than Cu(2+). The methylene blue adsorbed onto the hydrogel
      membrane can be photocatalytically degraded by Fenton agent and the hydrogel
      membrane could be recycled at least five times without obvious loss in mechanical
      properties. In conclusion, this presentation demonstrates a convenient strategy
      to prepare tough and elastic clay nanocomposite hydrogel, which can not only be
      applied as recyclable membrane for the photocatalytic degradation of organic dye,
      but also for the recovery of valuables. 

PMID- 24586397
TI  - HIV-associated disruption of tight and adherens junctions of oral epithelial
      cells facilitates HSV-1 infection and spread.
AB  - Herpes simplex virus (HSV) types 1 and 2 are the most common opportunistic
      infections in HIV/AIDS. In these immunocompromised individuals, HSV-1 reactivates
      and replicates in oral epithelium, leading to oral disorders such as ulcers,
      gingivitis, and necrotic lesions. Although the increased risk of HSV infection
      may be mediated in part by HIV-induced immune dysfunction, direct or indirect
      interactions of HIV and HSV at the molecular level may also play a role. In this
      report we show that prolonged interaction of the HIV proteins tat and gp120 and
      cell-free HIV virions with polarized oral epithelial cells leads to disruption of
      tight and adherens junctions of epithelial cells through the mitogen-activated
      protein kinase signaling pathway. HIV-induced disruption of oral epithelial
      junctions facilitates HSV-1 paracellular spread between the epithelial cells.
      Furthermore, HIV-associated disruption of adherens junctions exposes sequestered
      nectin-1, an adhesion protein and critical receptor for HSV envelope glycoprotein
      D (gD). Exposure of nectin-1 facilitates binding of HSV-1 gD, which substantially
      increases HSV-1 infection of epithelial cells with disrupted junctions over that
      of cells with intact junctions. Exposed nectin-1 from disrupted adherens
      junctions also increases the cell-to-cell spread of HSV-1 from infected to
      uninfected oral epithelial cells. Antibodies to nectin-1 and HSV-1 gD
      substantially reduce HSV-1 infection and cell-to-cell spread, indicating that HIV
      promoted HSV infection and spread are mediated by the interaction of HSV gD with
      HIV-exposed nectin-1. Our data suggest that HIV-associated disruption of oral
      epithelial junctions may potentiate HSV-1 infection and its paracellular and cell
      to-cell spread within the oral mucosal epithelium. This could be one of the
      possible mechanisms of rapid development of HSV-associated oral lesions in HIV
      infected individuals. 

PMID- 24586398
TI  - RNA-seq analysis of transcriptome and glucosinolate metabolism in seeds and
      sprouts of broccoli (Brassica oleracea var. italic).
AB  - BACKGROUND: Broccoli (Brassica oleracea var. italica), a member of Cruciferae, is
      an important vegetable containing high concentration of various nutritive and
      functional molecules especially the anticarcinogenic glucosinolates. The sprouts
      of broccoli contain 10-100 times higher level of glucoraphanin, the main
      contributor of the anticarcinogenesis, than the edible florets. Despite the
      broccoli sprouts' functional importance, currently available genetic and genomic
      tools for their studies are very limited, which greatly restricts the development
      of this functionally important vegetable. RESULTS: A total of ~85 million 251 bp
      reads were obtained. After de novo assembly and searching the assembled
      transcripts against the Arabidopsis thaliana and NCBI nr databases, 19,441 top
      hit transcripts were clustered as unigenes with an average length of 2,133 bp.
      These unigenes were classified according to their putative functional categories.
      Cluster analysis of total unigenes with similar expression patterns and
      differentially expressed unigenes among different tissues, as well as
      transcription factor analysis were performed. We identified 25 putative
      glucosinolate metabolism genes sharing 62.04-89.72% nucleotide sequence identity
      with the Arabidopsis orthologs. This established a broccoli glucosinolate
      metabolic pathway with high colinearity to Arabidopsis. Many of the biosynthetic
      and degradation genes showed higher expression after germination than in seeds;
      especially the expression of the myrosinase TGG2 was 20-130 times higher. These
      results along with the previous reports about these genes' studies in Arabidopsis
      and the glucosinolate concentration in broccoli sprouts indicate the breakdown
      products of glucosinolates may play important roles in the stage of broccoli seed
      germination and sprout development. CONCLUSION: Our study provides the largest
      genetic resource of broccoli to date. These data will pave the way for further
      studies and genetic engineering of broccoli sprouts and will also provide new
      insight into the genomic research of this species and its relatives.

PMID- 24586399
TI  - Molecular phylogenetics and temporal diversification in the genus Aeromonas based
      on the sequences of five housekeeping genes.
AB  - Several approaches have been developed to estimate both the relative and absolute
      rates of speciation and extinction within clades based on molecular phylogenetic
      reconstructions of evolutionary relationships, according to an underlying model
      of diversification. However, the macroevolutionary models established for
      eukaryotes have scarcely been used with prokaryotes. We have investigated the
      rate and pattern of cladogenesis in the genus Aeromonas (gamma-Proteobacteria,
      Proteobacteria, Bacteria) using the sequences of five housekeeping genes and an
      uncorrelated relaxed-clock approach. To our knowledge, until now this analysis
      has never been applied to all the species described in a bacterial genus and thus
      opens up the possibility of establishing models of speciation from sequence data
      commonly used in phylogenetic studies of prokaryotes. Our results suggest that
      the genus Aeromonas began to diverge between 248 and 266 million years ago,
      exhibiting a constant divergence rate through the Phanerozoic, which could be
      described as a pure birth process. 

PMID- 24586400
TI  - Ischaemic strokes in patients with pulmonary arteriovenous malformations and
      hereditary hemorrhagic telangiectasia: associations with iron deficiency and
      platelets.
AB  - BACKGROUND: Pulmonary first pass filtration of particles marginally exceeding ~7
      um (the size of a red blood cell) is used routinely in diagnostics, and allows
      cellular aggregates forming or entering the circulation in the preceding cardiac
      cycle to lodge safely in pulmonary capillaries/arterioles. Pulmonary
      arteriovenous malformations compromise capillary bed filtration, and are commonly
      associated with ischaemic stroke. Cohorts with CT-scan evident malformations
      associated with the highest contrast echocardiographic shunt grades are known to
      be at higher stroke risk. Our goal was to identify within this broad grouping,
      which patients were at higher risk of stroke. METHODOLOGY: 497 consecutive
      patients with CT-proven pulmonary arteriovenous malformations due to hereditary
      haemorrhagic telangiectasia were studied. Relationships with radiologically
      confirmed clinical ischaemic stroke were examined using logistic regression,
      receiver operating characteristic analyses, and platelet studies. PRINCIPAL
      FINDINGS: Sixty-one individuals (12.3%) had acute, non-iatrogenic ischaemic
      clinical strokes at a median age of 52 (IQR 41-63) years. In crude and age
      adjusted logistic regression, stroke risk was associated not with venous
      thromboemboli or conventional neurovascular risk factors, but with low serum iron
      (adjusted odds ratio 0.96 [95% confidence intervals 0.92, 1.00]), and more weakly
      with low oxygen saturations reflecting a larger right-to-left shunt (adjusted OR
      0.96 [0.92, 1.01]). For the same pulmonary arteriovenous malformations, the
      stroke risk would approximately double with serum iron 6 umol/L compared to mid
      normal range (7-27 umol/L). Platelet studies confirmed overlooked data that iron
      deficiency is associated with exuberant platelet aggregation to serotonin (5HT),
      correcting following iron treatment. By MANOVA, adjusting for participant and
      5HT, iron or ferritin explained 14% of the variance in log-transformed
      aggregation-rate (p = 0.039/p = 0.021). SIGNIFICANCE: These data suggest that
      patients with compromised pulmonary capillary filtration due to pulmonary
      arteriovenous malformations are at increased risk of ischaemic stroke if they are
      iron deficient, and that mechanisms are likely to include enhanced aggregation of
      circulating platelets.

PMID- 24586401
TI  - Neutrality, cross-immunity and subtype dominance in avian influenza viruses.
AB  - Avian influenza viruses (AIVs) are considered a threat for their potential to
      seed human influenza pandemics. Despite their acknowledged importance, there are
      significant unknowns regarding AIV transmission dynamics in their natural hosts,
      wild birds. Of particular interest is the difference in subtype dynamics between
      human and bird populations-in human populations, typically only two or three
      subtypes cocirculate, while avian populations are capable of simultaneously
      hosting a multitude of subtypes. One species in particular-ruddy turnstones
      (Arenaria interpres)--has been found to harbour a very wide range of AIV
      subtypes, which could make them a key player in the spread of new subtypes in
      wild bird populations. Very little is known about the mechanisms that drive
      subtype dynamics in this species, and here we address this gap in our knowledge.
      Taking advantage of two independent sources of data collected from ruddy
      turnstones in Delaware Bay, USA, we examine patterns of subtype diversity and
      dominance at this site. We compare these patterns to those produced by a
      stochastic, multi-strain transmission model to investigate possible mechanisms
      that are parsimonious with the observed subtype dynamics. We find, in agreement
      with earlier experimental work, that subtype differences are unnecessary to
      replicate the observed dynamics, and that neutrality alone is sufficient. We also
      evaluate the role of subtype cross-immunity and find that it is not necessary to
      generate patterns consistent with observations. This work offers new insights
      into the mechanisms behind subtype diversity and dominance in a species that has
      the potential to be a key player in AIV dynamics in wild bird populations.

PMID- 24586403
TI  - Inferring fish escape behaviour in trawls based on catch comparison data: model
      development and evaluation based on data from Skagerrak, Denmark.
AB  - During the fishing process, fish react to a trawl with a series of behaviours
      that often are species and size specific. Thus, a thorough understanding of fish
      behaviour in relation to fishing gear and a scientific understanding of the
      ability of different gear designs to utilize or stimulate various behavioural
      patterns during the catching process are essential for developing more efficient,
      selective, and environmentally friendly trawls. Although many behavioural studies
      using optical and acoustic observation systems have been conducted, harsh
      observation conditions on the fishing grounds often hamper the ability to
      directly observe fish behaviour in relation to fishing gear. As an alternative to
      optical and acoustic methods, we developed and applied a new mathematical model
      to catch data to extract detailed and quantitative information about species- and
      size-dependent escape behaviour in towed fishing gear such as trawls. We used
      catch comparison data collected with a twin trawl setup; the only difference
      between the two trawls was that a 12 m long upper section was replaced with 800
      mm diamond meshes in one of them. We investigated the length-based escape
      behaviour of cod (Gadus morhua), haddock (Melanogrammus aeglefinus), saithe
      (Pollachius virens), witch flounder (Glyptocephalus cynoglossus), and lemon sole
      (Microstomus kitt) and quantified the extent to which behavioural responses set
      limits for the large mesh panel's selective efficiency. Around 85% of saithe, 80%
      of haddock, 44% of witch flounder, 55% of lemon sole, and 55% of cod (below 68
      cm) contacted the large mesh panel and escaped. We also demonstrated the need to
      account for potential selectivity in the trawl body, as it can bias the
      assessment of length-based escape behaviour. Our indirect assessment of fish
      behaviour was in agreement with the direct observations made for the same species
      in a similar section of the trawl body reported in the literature. 

PMID- 24586402
TI  - Aberrant bone density in aging mice lacking the adenosine transporter ENT1.
AB  - Adenosine is known to regulate bone production and resorption in humans and mice.
      Type 1 equilibrative nucleoside transporter (ENT1) is responsible for the
      majority of adenosine transport across the plasma membrane and is ubiquitously
      expressed in both humans and mice. However, the contribution of ENT1-mediated
      adenosine levels has not been studied in bone remodeling. With the recent
      identification of the importance of adenosine signaling in bone homeostasis, it
      is essential to understand the role of ENT1 to develop novel therapeutic
      compounds for bone disorders. Here we examined the effect of ENT1 deletion on
      bone density using X-ray, dual energy X-ray absorptiometry and micro-computerized
      tomography analysis. Our results show that bone density and bone mineral density
      is reduced in the lower thoracic and lumbar spine as well as the femur of old
      ENT1 null mice (>7 months) compared to wild-type littermates. Furthermore, we
      found increased mRNA expression of tartrate-resistant acid phosphatase (TRAP), an
      osteoclast marker, in isolated long bones from 10 month old ENT1 null mice
      compared to wild-type mice. In addition, aged ENT1 null mice displayed severe
      deficit in motor coordination and locomotor activity, which might be attributed
      to dysregulated bone density. Overall, our study suggests that ENT1-regulated
      adenosine signaling plays an essential role in lumbar spine and femur bone
      density. 

PMID- 24586404
TI  - The vigilance decrement in executive function is attenuated when individual
      chronotypes perform at their optimal time of day.
AB  - Time of day modulates our cognitive functions, especially those related to
      executive control, such as the ability to inhibit inappropriate responses.
      However, the impact of individual differences in time of day preferences (i.e.
      morning vs. evening chronotype) had not been considered by most studies. It was
      also unclear whether the vigilance decrement (impaired performance with time on
      task) depends on both time of day and chronotype. In this study, morning-type and
      evening-type participants performed a task measuring vigilance and response
      inhibition (the Sustained Attention to Response Task, SART) in morning and
      evening sessions. The results showed that the vigilance decrement in inhibitory
      performance was accentuated at non-optimal as compared to optimal times of day.
      In the morning-type group, inhibition performance decreased linearly with time on
      task only in the evening session, whereas in the morning session it remained more
      accurate and stable over time. In contrast, inhibition performance in the evening
      type group showed a linear vigilance decrement in the morning session, whereas in
      the evening session the vigilance decrement was attenuated, following a quadratic
      trend. Our findings imply that the negative effects of time on task in executive
      control can be prevented by scheduling cognitive tasks at the optimal time of day
      according to specific circadian profiles of individuals. Therefore, time of day
      and chronotype influences should be considered in research and clinical studies
      as well as real-word situations demanding executive control for response
      inhibition. 

PMID- 24586405
TI  - Association between MTHFR polymorphisms and acute myeloid leukemia risk: a meta
      analysis.
AB  - Previous observational studies investigating the association between
      methylenetetrahydrofolate reductase (MTHFR) polymorphisms and acute myeloid
      leukemia risk (AML) have yielded inconsistent results. The aim of this study is
      to derive a more precise estimation of the association between MTHFR (C677T and
      A1298C) polymorphisms and acute myeloid leukemia risk. PubMed and Embase
      databases were systematically searched to identify relevant studies from their
      inception to August 2013. Odds ratios (ORs) with 95% confidence intervals (CIs)
      were the metric of choice. Thirteen studies were selected for C677T polymorphism
      (1838 cases and 5318 controls) and 9 studies (1335 patients and 4295 controls)
      for A1298C polymorphism. Overall, pooled results showed that C677T polymorphism
      was not significant associated with AML risk(OR, 0.98-1.04; 95% CI, 0.86-0.92 to
      1.09-1.25). Similar results were observed for the A1298C polymorphism and in
      subgroup analysis. All comparisons revealed no substantial heterogeneity nor did
      we detect evidence of publication bias. In summary, this meta-analysis provides
      evidence that MTHFR polymorphisms were not associated with AML risk. Further
      investigations are needed to offer better insight into the role of these
      polymorphisms in AML carcinogenesis. 

PMID- 24586406
TI  - Effective dysphonia detection using feature dimension reduction and kernel
      density estimation for patients with Parkinson's disease.
AB  - Detection of dysphonia is useful for monitoring the progression of phonatory
      impairment for patients with Parkinson's disease (PD), and also helps assess the
      disease severity. This paper describes the statistical pattern analysis methods
      to study different vocal measurements of sustained phonations. The feature
      dimension reduction procedure was implemented by using the sequential forward
      selection (SFS) and kernel principal component analysis (KPCA) methods. Four
      selected vocal measures were projected by the KPCA onto the bivariate feature
      space, in which the class-conditional feature densities can be approximated with
      the nonparametric kernel density estimation technique. In the vocal pattern
      classification experiments, Fisher's linear discriminant analysis (FLDA) was
      applied to perform the linear classification of voice records for healthy control
      subjects and PD patients, and the maximum a posteriori (MAP) decision rule and
      support vector machine (SVM) with radial basis function kernels were employed for
      the nonlinear classification tasks. Based on the KPCA-mapped feature densities,
      the MAP classifier successfully distinguished 91.8% voice records, with a
      sensitivity rate of 0.986, a specificity rate of 0.708, and an area value of 0.94
      under the receiver operating characteristic (ROC) curve. The diagnostic
      performance provided by the MAP classifier was superior to those of the FLDA and
      SVM classifiers. In addition, the classification results indicated that gender is
      insensitive to dysphonia detection, and the sustained phonations of PD patients
      with minimal functional disability are more difficult to be correctly identified.

PMID- 24586407
TI  - C. elegans CEP-1/p53 and BEC-1 are involved in DNA repair.
AB  - p53 is a transcription factor that regulates the response to cellular stress.
      Mammalian p53 functions as a tumor suppressor. The C. elegans p53, cep-1,
      regulates DNA-damage induced germline cell death by activating the transcription
      of egl-1 and ced-13. We used the C. elegans model to investigate how, in the
      whole animal, different forms of DNA damage can induce p53-dependent versus p53
      independent cell death and DNA repair. DNA damage was induced by ultraviolet type
      C (UVC) radiation, or 10-decarbamoyl mitomycin C (DMC, an agent known to induce
      mammalian p53-independent cell death). Wild-type or cep-1 loss-of-function mutant
      animals were assayed for germline cell death and DNA lesions. Wild-type animals
      displayed greater removal of UVC-lesions over time, whereas cep-1 mutant animals
      displayed increased UVC-lesion retention. The cep-1 mutation increased UVC-lesion
      retention directly correlated with a reduction of progeny viability. Consistent
      with DMC inducing p53-independent cell death in mammalian cells DMC induced a C.
      elegans p53-independent germline cell death pathway. To examine the influence of
      wild-type CEP-1 and DNA damage on C. elegans tumors we used glp-1(ar202gf)/Notch
      germline tumor mutants. UVC treatment of glp-1 mutant animals activated the CEP-1
      target gene egl-1 and reduced tumor size. In cep-1(gk138);glp-1(ar202gf) animals,
      UVC treatment resulted in increased susceptibility to lesions and larger tumorous
      germlines. Interestingly, the partial knockdown of bec-1 in adults resulted in a
      CEP-1-dependent increase in germline cell death and an increase in DNA damage.
      These results strongly support cross-talk between BEC-1 and CEP-1 to protect the
      C. elegans genome. 

PMID- 24586408
TI  - Chronic hepatitis B prevalence among children and mothers: results from a
      nationwide, population-based survey in Lao People's Democratic Republic.
AB  - BACKGROUND: Hepatitis B is regarded as a serious public health issue in Lao
      People's Democratic Republic (Lao PDR), a Southeast Asian country. However,
      disease epidemiology among the general population is not well known, and thus a
      nationwide cross-sectional survey for hepatitis B surface antigen (HBsAg)
      prevalence in children and their mothers was conducted. METHODS AND FINDINGS: We
      applied three-stage cluster sampling using probability proportionate to size.
      After randomly selecting child (5 to 9 years old) and mother (15 to 45 years old)
      pairs from the selected villages, questionnaires and HBsAg rapid tests were
      conducted. Data from 965 child and mother pairs were analyzed. Multivariate
      logistic regression analyses were used to investigate the independent association
      of individual background characteristics for the odds of being HBsAg positive. In
      total, 17 children and 27 mothers were HBsAg positive. HBsAg prevalence was
      estimated to be 1.7% (95% confidence interval: 0.8%-2.6%) in children, and 2.9%
      (95% confidence interval: 1.7%-4.2%) in their mothers after taking sampling
      design and weight of each sample into account. Mother's infection status was
      positively associated with HBsAg positivity in children (p<0.001), whereas other
      potential risk factors, such as ethnicity, proximity to health centers, and
      history of surgery, were not. There were no significant associations between
      mother's HBsAg status and history of surgery, and other sociodemographic factors.
      CONCLUSIONS: Despite the slow implementation of the hepatitis B vaccination
      program, HBsAg prevalence among children and their mothers was not high in Lao
      PDR compared to reports from neighboring countries. The reasons for the
      differences in prevalence among these countries are unclear. We recommend that
      prevalence surveys be conducted in populations born before and after the
      implementation of a hepatitis B vaccination program to better understand the
      epidemiology of hepatitis B.

PMID- 24586409
TI  - Allometries of maximum growth rate versus body mass at maximum growth indicate
      that non-avian dinosaurs had growth rates typical of fast growing ectothermic
      sauropsids.
AB  - We tested if growth rates of recent taxa are unequivocally separated between
      endotherms and ectotherms, and compared these to dinosaurian growth rates. We
      therefore performed linear regression analyses on the log-transformed maximum
      growth rate against log-transformed body mass at maximum growth for extant
      altricial birds, precocial birds, eutherians, marsupials, reptiles, fishes and
      dinosaurs. Regression models of precocial birds (and fishes) strongly differed
      from Case's study (1978), which is often used to compare dinosaurian growth rates
      to those of extant vertebrates. For all taxonomic groups, the slope of 0.75
      expected from the Metabolic Theory of Ecology was statistically supported. To
      compare growth rates between taxonomic groups we therefore used regressions with
      this fixed slope and group-specific intercepts. On average, maximum growth rates
      of ectotherms were about 10 (reptiles) to 20 (fishes) times (in comparison to
      mammals) or even 45 (reptiles) to 100 (fishes) times (in comparison to birds)
      lower than in endotherms. While on average all taxa were clearly separated from
      each other, individual growth rates overlapped between several taxa and even
      between endotherms and ectotherms. Dinosaurs had growth rates intermediate
      between similar sized/scaled-up reptiles and mammals, but a much lower rate than
      scaled-up birds. All dinosaurian growth rates were within the range of extant
      reptiles and mammals, and were lower than those of birds. Under the assumption
      that growth rate and metabolic rate are indeed linked, our results suggest two
      alternative interpretations. Compared to other sauropsids, the growth rates of
      studied dinosaurs clearly indicate that they had an ectothermic rather than an
      endothermic metabolic rate. Compared to other vertebrate growth rates, the
      overall high variability in growth rates of extant groups and the high overlap
      between individual growth rates of endothermic and ectothermic extant species
      make it impossible to rule out either of the two thermoregulation strategies for
      studied dinosaurs. 

PMID- 24586410
TI  - Data simulation in machine olfaction with the R package chemosensors.
AB  - In machine olfaction, the design of applications based on gas sensor arrays is
      highly dependent on the robustness of the signal and data processing algorithms.
      While the practice of testing the algorithms on public benchmarks is not common
      in the field, we propose software for performing data simulations in the machine
      olfaction field by generating parameterized sensor array data. The software is
      implemented as an R language package chemosensors which is open-access, platform
      independent and self-contained. We introduce the concept of a virtual sensor
      array which can be used as a data generation tool. In this work, we describe the
      data simulation workflow which basically consists of scenario definition, virtual
      array parameterization and the generation of sensor array data. We also give
      examples of the processing of the simulated data as proof of concept for the
      parameterized sensor array data: the benchmarking of classification algorithms,
      the evaluation of linear- and non-linear regression algorithms, and the
      biologically inspired processing of sensor array data. All the results presented
      were obtained under version 0.7.6 of the chemosensors package whose home page is
      chemosensors.r-forge.r-project.org. 

PMID- 24586411
TI  - A palindromic CpG-containing phosphodiester oligodeoxynucleotide as a mucosal
      adjuvant stimulates plasmacytoid dendritic cell-mediated T(H)1 immunity.
AB  - BACKGROUND: CpG oligodeoxynucleotides (ODNs), resembling bacterial DNA, are
      currently tested in clinical trials as vaccine adjuvants. They have the nuclease
      resistant phosphorothioate bond; the immune responses elicited differ according
      to the CpG ODN sequence and vaccination method. To develop a CpG ODN that can
      induce plasmacytoid dendritic cell (pDC)-mediated T(H)1 immunity through the
      mucosa, we constructed phosphodiester G9.1 comprising one palindromic CpG motif
      with unique polyguanosine-runs that allows degradation similar to naturally
      occurring bacterial DNA. METHODS: T(H)1 and T(H)2 immunity activation was
      evaluated by cytokine production pattern and T-bet/GATA-3 ratio in human
      peripheral blood mononuclear cells and mouse bone marrow cells. Adjuvanticity was
      evaluated in mice administered G9.1 with diphtheria toxoid (DT) through nasal
      vaccination. RESULTS: G9.1 exhibited stronger IFN-alpha-inducing activity than A
      class CpG ODN2216 and increased T-bet/GATA-3 ratio by enhancing T-bet expression.
      Nasally administered G9.1 plus DT induced DT-specific mucosal IgA and serum IgG,
      but not IgE, responses with antitoxin activity in C57BL/6 and BALB/c mice,
      possibly due to IFN/BAFF production. Induction of T(H)1, but not T(H)2-type Abs
      depended completely on pDCs, the first in vivo demonstration by CpG ODNs.
      CONCLUSIONS: G9.1 is a promising mucosal adjuvant for induction of pDC-mediated
      T(H)1 immunity.

PMID- 24586412
TI  - Analysis of Notch signaling-dependent gene expression in developing airways
      reveals diversity of Clara cells.
AB  - Clara cells (CCs) are a morphologically and operationally heterogeneous
      population of Secretoglobin Scgb1a1-expressing secretory cells that are crucial
      for airway homeostasis and post-injury repair. Analysis of the extent and origin
      of CC diversity are limited by knowledge of genes expressed in these cells and
      their precursors. To identify novel putative markers of CCs and explore the
      origins of CC diversity, we characterized global changes in gene expression in
      embryonic lungs in which CCs do not form due to conditional disruption of Notch
      signaling (Rbpjk(CNULL)). Microarray profiling, Real Time PCR (qRT-PCR), and RNA
      in situ hybridization (ISH) identified eleven genes downregulated in the E18.5
      airways of Rbpjk(cnull) compared to controls, nearly half not previously known to
      mark CCs. ISH revealed that several genes had overlapping but distinct domains of
      expression of in the normal developing lung (E18.5). Notably, Reg3g, Chad, Gabrp
      and Lrrc26 were enriched in proximal airways, Hp in the distal airways and Upk3a
      in clusters of cells surrounding Neuroepithelial Bodies (NEBs). Seven of the
      eleven genes, including Reg3g, Hp, and Upk3a, were expressed in the adult lung in
      CCs in a pattern similar to that observed in the developing airways. qRT-PCR
      based analysis of gene expression of CCs isolated from different airway regions
      of B1-EGFP reporter mice corroborated the spatial enrichment in gene expression
      observed by ISH. Our study identifies candidate markers for CC-precursors and CCs
      and supports the idea that the diversification of the CC phenotype occurs already
      during embryonic development. 

PMID- 24586413
TI  - Relationship between impulsivity, snack consumption and children's weight.
AB  - BACKGROUND: Childhood overweight is a public health problem associated with
      psychosocial and physical problems. Personality traits, such as impulsivity, may
      contribute to the development of overweight. OBJECTIVE: This study examines 1)
      the association between general impulsivity traits (reward sensitivity and
      disinhibition) and children's weight, 2) the association between impulsivity
      traits and unhealthy snack consumption, and 3) the potential mediating role of
      unhealthy snack consumption in the relationship between impulsivity traits and
      children's weight. METHODS: Included were 1,377 parent-child dyads participating
      in the IVO Nutrition and Physical Activity Child cohorT (INPACT). Children had a
      mean age of 10 years. Parents completed a questionnaire to measure children's
      unhealthy snack consumption. Children completed a door-opening task to assess
      reward sensitivity and completed a questionnaire to measure disinhibition.
      Children's height and weight were measured to calculate their BMI z-scores. Cross
      sectional linear regression analyses were performed to test the associations.
      RESULTS: Disinhibition was positively associated with unhealthy snack consumption
      but not with BMI z-scores. Reward sensitivity was not related to unhealthy snack
      consumption or to BMI z-scores. CONCLUSIONS: No evidence was found for a
      mediating effect of unhealthy snack consumption in the relation between
      impulsivity traits and children's weight. However, disinhibition appears to have
      a negative influence on children's unhealthy snack consumption. Future research
      focusing on food-related impulsivity in addition to general impulsivity will
      provide additional insight into factors that influence children's unhealthy snack
      consumption and weight.

PMID- 24586414
TI  - The impact of weather on women's tendency to wear red or pink when at high risk
      for conception.
AB  - Women are particularly motivated to enhance their sexual attractiveness during
      their most fertile period, and men perceive shades of red, when associated with
      women, as sexually attractive. Building on this research, we recently found that
      women are more likely to wear reddish clothing when at peak fertility (Beall &
      Tracy, 2013), presumably as a way of increasing their attractiveness. Here, we
      first report results from a methodological replication, conducted during warmer
      weather, which produced a null effect. Investigating this discrepancy, we
      considered the impact of a potentially relevant contextual difference between
      previous research and the replication: current weather. If the red-dress effect
      is driven by a desire to increase one's sexual appeal, then it should emerge most
      reliably when peak-fertility women have few alternative options for accomplishing
      this goal (e.g., wearing minimal clothing). Results from re-analyses of our
      previously collected data and a new experiment support this account, by
      demonstrating that the link between fertility and red/pink dress emerges robustly
      in cold, but not warm, weather. Together, these findings suggest that the
      previously documented red-dress effect is moderated by current climate concerns,
      and provide further evidence that under certain circumstances red/pink dress is
      reliably associated with female fertility. 

PMID- 24586415
TI  - Single-cell resolution imaging of retinal ganglion cell apoptosis in vivo using a
      cell-penetrating caspase-activatable peptide probe.
AB  - Peptide probes for imaging retinal ganglion cell (RGC) apoptosis consist of a
      cell-penetrating peptide targeting moiety and a fluorophore-quencher pair
      flanking an effector caspase consensus sequence. Using ex vivo fluorescence
      imaging, we previously validated the capacity of these probes to identify
      apoptotic RGCs in cell culture and in an in vivo rat model of N-methyl- D
      aspartate (NMDA)-induced neurotoxicity. Herein, using TcapQ488, a new probe
      designed and synthesized for compatibility with clinically-relevant imaging
      instruments, and real time imaging of a live rat RGC degeneration model, we fully
      characterized time- and dose-dependent probe activation, signal-to-noise ratios,
      and probe safety profiles in vivo. Adult rats received intravitreal injections of
      four NMDA concentrations followed by varying TcapQ488 doses. Fluorescence fundus
      imaging was performed sequentially in vivo using a confocal scanning laser
      ophthalmoscope and individual RGCs displaying activated probe were counted and
      analyzed. Rats also underwent electroretinography following intravitreal
      injection of probe. In vivo fluorescence fundus imaging revealed distinct single
      cell probe activation as an indicator of RGC apoptosis induced by intravitreal
      NMDA injection that corresponded to the identical cells observed in retinal flat
      mounts of the same eye. Peak activation of probe in vivo was detected 12 hours
      post probe injection. Detectable fluorescent RGCs increased with increasing NMDA
      concentration; sensitivity of detection generally increased with increasing
      TcapQ488 dose until saturating at 0.387 nmol. Electroretinography following
      intravitreal injections of TcapQ488 showed no significant difference compared
      with control injections. We optimized the signal-to-noise ratio of a caspase
      activatable cell penetrating peptide probe for quantitative non-invasive
      detection of RGC apoptosis in vivo. Full characterization of probe performance in
      this setting creates an important in vivo imaging standard for functional
      evaluation of future probe analogues and provides a basis for extending this
      strategy into glaucoma-specific animal models. 

PMID- 24586416
TI  - Heterosexual anal sex among female sex workers in high HIV prevalence states of
      India: need for comprehensive intervention.
AB  - INTRODUCTION: Role of vaginal sex in heterosexual transmission of HIV has been
      investigated but that of heterosexual anal sex (HAS) is not fully understood.
      This paper examines practice of HAS among Female Sex Workers (FSWs) and its
      correlates in India where the HIV epidemic is being primarily driven by core
      groups like FSWs. METHODS: Data for this paper are drawn from Round I survey of
      9667 FSWs in the Integrated Biological and Behavioral Assessment (IBBA) from 23
      districts of 4 high HIV prevalent states of India. Bivariate and multivariate
      analysis identified factors associated with HAS. RESULTS: Ever having anal sex
      was reported by 11.9% FSWs (95% CI: 11.3%-12.6%). Typology (AOR 2.20, 95% CI 1.64
      2.95) and literacy (AOR 1.28, 95% CI 1.10-1.49) were positively associated with
      practice of HAS. Longer duration in sex trade (AOR 1.69, 95% CI 1.44-1.99),
      entertaining larger number of clients the previous week (AOR 1.78, 95% CI 1.47
      2.15), alcohol consumption (AOR 1.21, 95% CI 1.03-1.42) and inability to
      negotiate condom use (AOR 1.53, 95% CI 1.28-1.83) were also correlated with HAS.
      Self-risk perception for HIV (AOR 1.46, 95% CI 1.25-1.71) did not impede HAS.
      Although symptoms of sexually transmitted infections (STIs) in the last 12 months
      were associated with anal sex (AOR 1.39, 95% CI 1.13-1.72) there was no
      significant association between laboratory confirmed HIV and other STIs with HAS.
      CONCLUSION: Practice of HAS by FSWs might significantly contribute to HIV
      transmission in India. This study also shows that despite self-risk perception
      for HIV, even literate FSWs with longer duration in sex work report HAS. General
      messages on condom use may not influence safe HAS. FSWs need to be targeted with
      specific messages on HIV transmission during anal sex. Women controlled
      prevention methods, such as rectal microbicides and vaginal microbicides are
      needed.

PMID- 24586417
TI  - Bovine papillomavirus type 2 (BPV-2) E5 oncoprotein binds to the subunit D of the
      V1-ATPase proton pump in naturally occurring urothelial tumors of the urinary
      bladder of cattle.
AB  - BACKGROUND: Active infection by bovine papillomavirus type 2 (BPV-2) was
      documented for fifteen urinary bladder tumors in cattle. Two were diagnosed as
      papillary urothelial neoplasm of low malignant potential (PUNLMP), nine as
      papillary and four as invasive urothelial cancers. METHODS AND FINDINGS: In all
      cancer samples, PCR analysis revealed a BPV-2-specific 503 bp DNA fragment. E5
      protein, the major oncoprotein of the virus, was shown both by
      immunoprecipitation and immunohistochemical analysis. E5 was found to bind to the
      activated (phosphorylated) form of the platelet derived growth factor beta
      receptor. PDGFbetaR immunoprecipitation from bladder tumor samples and from
      normal bladder tissue used as control revealed a protein band which was present
      in the pull-down from bladder cancer samples only. The protein was identified
      with mass spectrometry as "V1-ATPase subunit D", a component of the central stalk
      of the V1-ATPase vacuolar pump. The subunit D was confirmed in this complex by
      coimmunoprecipitation investigations and it was found to colocalize with the
      receptor. The subunit D was also shown to be overexpressed by Western blot, RT
      PCR and immunofluorescence analyses. Immunoprecipitation and immunofluorescence
      also revealed that E5 oncoprotein was bound to the subunit D. CONCLUSION: For the
      first time, a tri-component complex composed of E5/PDGFbetaR/subunit D has been
      documented in vivo. Previous in vitro studies have shown that the BPV-2 E5
      oncoprotein binds to the proteolipid c ring of the V0-ATPase sector. We suggest
      that the E5/PDGFbetaR/subunit D complex may perturb proteostasis, organelle and
      cytosol homeostasis, which can result in altered protein degradation and in
      autophagic responses.

PMID- 24586418
TI  - Production of hybrids between western gray wolves and western coyotes.
AB  - Using artificial insemination we attempted to produce hybrids between captive,
      male, western, gray wolves (Canis lupus) and female, western coyotes (Canis
      latrans) to determine whether their gametes would be compatible and the coyotes
      could produce and nurture offspring. The results contribute new information to an
      ongoing controversy over whether the eastern wolf (Canis lycaon) is a valid
      unique species that could be subject to the U. S. Endangered Species Act.
      Attempts with transcervically deposited wolf semen into nine coyotes over two
      breeding seasons yielded three coyote pregnancies. One coyote ate her pups,
      another produced a resorbed fetus and a dead fetus by C-section, and the third
      produced seven hybrids, six of which survived. These results show that, although
      it might be unlikely for male western wolves to successfully produce offspring
      with female western coyotes under natural conditions, western-gray-wolf sperm are
      compatible with western-coyote ova and that at least one coyote could produce and
      nurture hybrid offspring. This finding in turn demonstrates that gamete
      incompatibility would not have prevented western, gray wolves from inseminating
      western coyotes and thus producing hybrids with coyote mtDNA, a claim that
      counters the view that the eastern wolf is a separate species. However, some of
      the difficulties experienced by the other inseminated coyotes tend to temper that
      finding and suggest that more experimentation is needed, including determining
      the behavioral and physical compatibility of western gray wolves copulating with
      western coyotes. Thus although our study adds new information to the controversy,
      it does not settle it. Further study is needed to determine whether the putative
      Canis lycaon is indeed a unique species. 

PMID- 24586419
TI  - Kronecker product linear exponent AR(1) correlation structures for multivariate
      repeated measures.
AB  - Longitudinal imaging studies have moved to the forefront of medical research due
      to their ability to characterize spatio-temporal features of biological
      structures across the lifespan. Credible models of the correlations in
      longitudinal imaging require two or more pattern components. Valid inference
      requires enough flexibility of the correlation model to allow reasonable fidelity
      to the true pattern. On the other hand, the existence of computable estimates
      demands a parsimonious parameterization of the correlation structure. For many
      one-dimensional spatial or temporal arrays, the linear exponent autoregressive
      (LEAR) correlation structure meets these two opposing goals in one model. The
      LEAR structure is a flexible two-parameter correlation model that applies to
      situations in which the within-subject correlation decreases exponentially in
      time or space. It allows for an attenuation or acceleration of the exponential
      decay rate imposed by the commonly used continuous-time AR(1) structure. We
      propose the Kronecker product LEAR correlation structure for multivariate
      repeated measures data in which the correlation between measurements for a given
      subject is induced by two factors (e.g., spatial and temporal dependence).
      Excellent analytic and numerical properties make the Kronecker product LEAR model
      a valuable addition to the suite of parsimonious correlation structures for
      multivariate repeated measures data. Longitudinal medical imaging data of caudate
      morphology in schizophrenia illustrates the appeal of the Kronecker product LEAR
      correlation structure. 

PMID- 24586420
TI  - Resistance to mTOR kinase inhibitors in lymphoma cells lacking 4EBP1.
AB  - Inhibitors of the mechanistic target of rapamycin (mTOR) hold promise for
      treatment of hematological malignancies. Analogs of the allosteric mTOR inhibitor
      rapamycin are approved for mantle cell lymphoma but have limited efficacy in
      other blood cancers. ATP-competitive "active-site" mTOR inhibitors produce more
      complete mTOR inhibition and are more effective than rapamycin in preclinical
      models of leukemia, lymphoma and multiple myeloma. In parallel to clinical trials
      of active-site mTOR inhibitors, it will be important to identify resistance
      mechanisms that might limit drug efficacy in certain patients. From a panel of
      diffuse large B-cell lymphoma cell lines, we found that the VAL cell line is
      particularly resistant to apoptosis in the presence of active-site mTOR
      inhibitors. Mechanistic investigation showed that VAL does not express eukaryotic
      initiation factor 4E-binding protein-1 (4EBP1), a key negative regulator of
      translation controlled by mTOR. Although VAL cells express the related protein
      4EBP2, mTOR inhibitor treatment fails to displace eukaryotic initiation factor 4G
      from the mRNA cap-binding complex. Knockdown of eukaryotic initiation factor 4E,
      or re-expression of 4EBP1, sensitizes cells to apoptosis when treated with active
      site mTOR inhibitors. These findings provide a naturally occurring example of
      4EBP deficiency driving lymphoma cell resistance to active-site mTOR inhibitors. 

PMID- 24586421
TI  - Imaging dynamic molecular signaling by the Cdc42 GTPase within the developing
      CNS.
AB  - Protein interactions underlie the complexity of neuronal function. Potential
      interactions between specific proteins in the brain are predicted from assays
      based on genetic interaction and/or biochemistry. Genetic interaction reveals
      endogenous, but not necessarily direct, interactions between the proteins.
      Biochemistry-based assays, on the other hand, demonstrate direct interactions
      between proteins, but often outside their native environment or without a
      subcellular context. We aimed to achieve the best of both approaches by
      visualizing protein interaction directly within the brain of a live animal. Here,
      we show a proof-of-principle experiment in which the Cdc42 GTPase associates with
      its alleged partner WASp within neurons during the time and space that coincide
      with the newly developing CNS. 

PMID- 24586422
TI  - A novel method to apply osteogenic potential of adipose derived stem cells in
      orthopaedic surgery.
AB  - BACKGROUND: A number of publications have reported that adipose derived stem
      cells (ADSCs) have the capacity to be induced to differentiate into osteoblasts
      both in vitro and in vivo. However, it has been difficult to use separate ADSCs
      for cortical bone regeneration and bone reconstruction so far. Inspired by the
      research around stromal stem cells and cell sheets, we developed a new method to
      fabricate ADSCs sheets to accelerate and enhance the bone regeneration and bone
      reconstruction. PURPOSE: To fabricate ADSCs sheets and evaluate their capacity to
      be induced to differentiate to osteoblasts in vitro. METHODS: Human adipose
      derived stem cells (hADSCs) were employed in this research. The fabricating
      medium containing 50 uM ascorbate-2-phosphate was used to enhance the secretion
      of collagen protein by the ADSCs and thus to make the cell sheets of ADSCs. As
      the separate ADSCs were divided into osteo-induction group and control group, the
      ADSCs sheets were also divided into two groups depending on induction by
      osteogenesis medium or no induction. The osteogenic capacity of each group was
      evaluated by ALP staining, Alizarin Red staining and ALP activity. RESULTS: The
      ADSCs sheets were fabricated after one-week culture in the fabricating medium.
      The ALP staining of ADSCs sheets showed positive results after 5 days osteo
      induction and the Alizarin Red staining of ADSCs sheets showed positive results
      after 1 week osteo-induction. The ALP activity showed significant differences
      between these four groups. The ALP activity of ADSCs sheets groups showed higher
      value than that of separate ADSCs. CONCLUSION: The experiments demonstrated that
      ADSCs sheets have better capacity than separate ADSCs to be induced to
      differentiate into osteoblasts. This indicates that it is possible to use the
      ADSCs sheets as a source of mesenchymal stem cells for bone regeneration and bone
      reconstruction.

PMID- 24586423
TI  - Treatment and outcomes among patients with Cryptococcus gattii infections in the
      United States Pacific Northwest.
AB  - BACKGROUND: Cryptococcus gattii is a fungal pathogen causing an emerging outbreak
      in the United States Pacific Northwest (PNW). Treatment guidelines for
      cryptococcosis are primarily based on data from C. neoformans infections;
      applicability to PNW C. gattii infection is unknown. We evaluated the
      relationship between initial antifungal treatment and outcomes for PNW C. gattii
      patients. METHODS: Cases were defined as culture-confirmed invasive C. gattii
      infections among residents of Oregon and Washington States during 2004-2011.
      Clinical data were abstracted from medical records through one year of follow-up.
      Recommended initial treatment for central nervous system (CNS), bloodstream, and
      severe pulmonary infections is amphotericin B and 5-flucytosine; for non-severe
      pulmonary infections, recommended initial treatment is fluconazole. Alternative
      initial treatment was defined as any other initial antifungal treatment. RESULTS:
      Seventy patients survived to diagnosis; 50 (71%) received the recommended initial
      treatment and 20 (29%) received an alternative. Fewer patients with pulmonary
      infections [21 (64%)] than CNS infections [25 (83%)] received the recommended
      initial treatment (p = 0.07). Among patients with pulmonary infections, those
      with severe infections received the recommended initial treatment less often than
      those with non-severe infections (11% vs. 83%, p<0.0001). Eight patients with
      severe pulmonary infections received alternative initial treatments; three died.
      Four patients with non-severe pulmonary infections received alternative initial
      treatments; two died. There was a trend towards increased three-month mortality
      among patients receiving alternative vs. recommended initial treatment (30% vs.
      14%, p = 0.12), driven primarily by increased mortality among patients with
      pulmonary disease receiving alternative vs. recommended initial treatment (42%
      vs. 10%, p = 0.07). CONCLUSIONS: C. gattii patients with pulmonary infections-
      especially severe infections--may be less likely to receive recommended treatment
      than those with CNS infections; alternative treatment may be associated with
      increased mortality. Reasons for receipt of alternative treatment among C. gattii
      patients in this area should be investigated, and clinician awareness of
      recommended treatment reinforced.

PMID- 24586424
TI  - Association of vitamin D and incident statin induced myalgia--a retrospective
      cohort study.
AB  - BACKGROUND AND OBJECTIVES: Evidence is conflicting with regards to the role of
      vitamin D in statin induced myalgia (SIM). Studies so far have assessed cross
      sectional association and were limited by study sample selected predominantly
      from cardiology clinics. In this retrospective cohort study we assessed the
      association between vitamin D and SIM and attempted to establish a serum vitamin
      D cutoff to identify patients at risk for developing SIM. METHODS: Medical charts
      of 5526 consecutive patients from a primary care practice in Scranton,
      Pennsylvania from 2005-2012 were reviewed. Vitamin D level (25-hydroxy
      cholecalciferol) at statin initiation was considered "Exposure level". Vitamin D
      levels were categorized into quartiles (<= 10, 11-20, 21-30, >30 ng/ml). SIM was
      identified by patient report. RESULTS: 1160 out of 5526 patients were treated
      with statins. The mean age was 55.9 years. 276 (24%) developed SIM. Unadjusted 7
      yr cumulative incidences of SIM for quartiles 1-4 of vitamin D were 32.3, 21.5,
      18.3 and 14.6% respectively. The lowest quartile of vitamin D was independently
      associated with 1.21 times the hazard of the fourth quartile for developing SIM
      (95% CI: 1.09, 1.33; P-trend  = 0.001). Vitamin D cut-off <=15 ng/ml, showed a
      positive predictive value, negative predictive value, likelihood ratio (LR) + and
      LR- of 81, 90, 5.1 and 0.1, respectively for predicting SIM. CONCLUSIONS: Low
      vitamin D level at statin initiation is associated with SIM, levels <=15 ng/ml
      have a high predictive accuracy for SIM. Randomized controlled trials are needed
      to validate our results.

PMID- 24586425
TI  - The G516T CYP2B6 germline polymorphism affects the risk of acute myeloid leukemia
      and is associated with specific chromosomal abnormalities.
AB  - The etiology of acute myeloid leukemia (AML) underlies the influence of genetic
      variants in candidate genes. The CYP2B6 enzyme detoxifies many genotoxic
      xenobiotics, protecting cells from oxidative damage. The CYP2B6 gene is subjected
      to a single-nucleotide polymorphism (G516T) with heterozygotes (GT) and
      homozygotes (TT) presenting decreased enzymatic activity. This case-control study
      aimed to investigate the association of CYP2B6 G516T polymorphism with the
      susceptibility of AML and its cytogenetic and clinical characteristics.
      Genotyping was performed on 619 AML patients and 430 healthy individuals using
      RCR-RFLP and a novel LightSNip assay. The major finding was a statistically
      higher frequency of the variant genotypes (GT and TT) in patients compared to the
      controls (GT:38.8% vs 29.8% and TT:9.3% vs 5.3% respectively) (p<0.001). More
      specifically, a significantly higher frequency of GT+TT genotypes in de novo AML
      patients (46.6%) and an immensely high frequency of TT in secondary AML (s-AML)
      (20.5%) were observed. The statistical analysis showed that the variant T allele
      was approximately 1.5-fold and 2.4-fold higher in de novo and s-AML respectively
      than controls. Concerning FAB subtypes, the T allele presented an almost 2-fold
      increased in AML-M2. Interestingly, a higher incidence of the TT genotype was
      observed in patients with abnormal karyotypes. In particular, positive
      correlations of the mutant allele were found in patients carrying specific
      chromosomal aberrations [-7/del(7q), -5/del(5q), +8, +21 or t(8;21)], complex or
      monosomal karyotypes. Finally, a strikingly higher frequency of TT genotype was
      also observed in patients stratified to the poor risk group. In conclusion, our
      results provide evidence for the involvement of the CYP2B6 polymorphism in AML
      susceptibility and suggest a possible role of the CYP2B6 genetic background on
      the development of specific chromosomal aberrations.

PMID- 24586426
TI  - Economic outcomes of maintenance gefitinib for locally advanced/metastatic non
      small-cell lung cancer with unknown EGFR mutations: a semi-Markov model analysis.
AB  - BACKGROUND: Maintenance gefitinib significantly prolonged progression-free
      survival (PFS) compared with placebo in patients from eastern Asian with locally
      advanced/metastatic non-small-cell lung cancer (NSCLC) after four
      chemotherapeutic cycles (21 days per cycle) of first-line platinum-based
      combination chemotherapy without disease progression. The objective of the
      current study was to evaluate the cost-effectiveness of maintenance gefitinib
      therapy after four chemotherapeutic cycle's stand first-line platinum-based
      chemotherapy for patients with locally advanced or metastatic NSCLC with unknown
      EGFR mutations, from a Chinese health care system perspective. METHODS AND
      FINDINGS: A semi-Markov model was designed to evaluate cost-effectiveness of the
      maintenance gefitinib treatment. Two-parametric Weibull and Log-logistic
      distribution were fitted to PFS and overall survival curves independently. One
      way and probabilistic sensitivity analyses were conducted to assess the stability
      of the model designed. The model base-case analysis suggested that maintenance
      gefitinib would increase benefits in a 1, 3, 6 or 10-year time horizon, with
      incremental $184,829, $19,214, $19,328, and $21,308 per quality-adjusted life
      year (QALY) gained, respectively. The most sensitive influential variable in the
      cost-effectiveness analysis was utility of PFS plus rash, followed by utility of
      PFS plus diarrhoea, utility of progressed disease, price of gefitinib, cost of
      follow-up treatment in progressed survival state, and utility of PFS on oral
      therapy. The price of gefitinib is the most significant parameter that could
      reduce the incremental cost per QALY. Probabilistic sensitivity analysis
      indicated that the cost-effective probability of maintenance gefitinib was zero
      under the willingness-to-pay (WTP) threshold of $16,349 (3 * per-capita gross
      domestic product of China). The sensitivity analyses all suggested that the model
      was robust. CONCLUSIONS: Maintenance gefitinib following first-line platinum
      based chemotherapy for patients with locally advanced/metastatic NSCLC with
      unknown EGFR mutations is not cost-effective. Decreasing the price of gefitinib
      may be a preferential choice for meeting widely treatment demands in China.

PMID- 24586427
TI  - Analysis of changes in traumatic symptoms and daily life activity of children
      affected by the 2011 Japan earthquake and tsunami over time.
AB  - BACKGROUND: On March 11, 2011, Japan was struck by a massive earthquake and
      tsunami. The tsunami caused tremendous damage and traumatized a number of people,
      including children. This study aimed to compare traumatic symptoms and daily life
      activity among children 20 months after the 2011 Great East Japan Earthquake and
      Tsunami with those observed after 8 months. METHODS: The study comprised two
      groups. The first comprised 12,524 kindergarten, elementary school, and junior
      high school children in Ishinomaki City, Miyagi Prefecture, Japan, who were
      evaluated 8 months after the disaster. The second comprised 10,597 children from
      the same place who were evaluated 20 months after the disaster. The Post
      Traumatic Stress Symptoms for Children 15 items (PTSSC-15), a self-completion
      questionnaire on traumatic symptoms, and a questionnaire on children's daily life
      were distributed to the children. An effective response was obtained from 11,639
      (92.9%, 8 months after) and 10,597 (86.9%, 20 months after) children. RESULTS:
      The PTSSC-15 score was significantly higher in junior high school girls than in
      boys. The PTSSC-15 score was significantly higher in 4th-6th grade girls than in
      boys after 8 months. Elementary and junior high school children evaluated after
      20 months had a significantly lower PTSSC-15 score than those evaluated after 8
      months. The number of children having breakfast was significantly higher after 8
      months than that after 20 months. In both the groups, children of all grades who
      had breakfast had a significantly lower PTSSC-15 score than those who did not
      have breakfast. CONCLUSIONS: We conclude that traumatic symptoms and daily life
      activity of children who survived the earthquake and tsunami improved over time.

PMID- 24586428
TI  - Importin 7 and Nup358 promote nuclear import of the protein component of human
      telomerase.
AB  - In actively dividing eukaryotic cells, chromosome ends (telomeres) are subject to
      progressive shortening, unless they are maintained by the action of telomerase, a
      dedicated enzyme that adds DNA sequence repeats to chromosomal 3'end. For its
      enzymatic function on telomeres, telomerase requires nuclear import of its
      protein component (hTERT in human cells) and assembly with the RNA component,
      TERC. We now confirm a major nuclear localization signal (NLS) in the N-terminal
      region of hTERT and describe a novel one in the C-terminal part. Using an siRNA
      approach to deplete several import receptors, we identify importin 7 as a soluble
      nuclear transport factor that is required for efficient import. At the level of
      the nuclear pore complex (NPC), Nup358, a nucleoporin that forms the cytoplasmic
      filaments of the NPC, plays an important role in nuclear import of hTERT. A
      structure-function analysis of Nup358 revealed that the zinc finger region of the
      nucleoporin is of particular importance for transport of hTERT. Together, our
      study sheds light on the nuclear import pathway of hTERT. 

PMID- 24586429
TI  - The general composition of the faecal virome of pigs depends on age, but not on
      feeding with a probiotic bacterium.
AB  - BACKGROUND: The pig faecal virome, which comprises the community of viruses
      present in pig faeces, is complex and consists of pig viruses, bacteriophages,
      transiently passaged plant viruses and other minor virus species. Only little is
      known about factors influencing its general composition. Here, the effect of the
      probiotic bacterium Enterococcus faecium (E. faecium) NCIMB 10415 on the pig
      faecal virome composition was analysed in a pig feeding trial with sows and their
      piglets, which received either the probiotic bacterium or not. RESULTS: From 8
      pooled faecal samples derived from the feeding trial, DNA and RNA virus particles
      were prepared and subjected to process-controlled Next Generation Sequencing
      resulting in 390,650 sequence reads. In average, 14% of the reads showed
      significant sequence identities to known viruses. The percentage of detected
      mammalian virus sequences was highest (55-77%) in the samples of the youngest
      piglets and lowest (8-10%) in the samples of the sows. In contrast, the
      percentage of bacteriophage sequences increased from 22-44% in the youngest
      piglets to approximately 90% in the sows. The dominating mammalian viruses
      differed remarkably among 12 day-old piglets (kobuvirus), 54 day-old piglets
      (boca-, dependo- and pig stool-associated small circular DNA virus [PigSCV]) and
      the sows (PigSCV, circovirus and "circovirus-like" viruses CB-A and RW-A). In
      addition, the Shannon index, which reflects the diversity of sequences present in
      a sample, was generally higher for the sows as compared to the piglets. No
      consistent differences in the virome composition could be identified between the
      viromes of the probiotic bacterium-treated group and the control group.
      CONCLUSION: The analysis indicates that the pig faecal virome shows a high
      variability and that its general composition is mainly dependent on the age of
      the pigs. Changes caused by feeding with the probiotic bacterium E. faecium could
      not be demonstrated using the applied metagenomics method.

PMID- 24586430
TI  - Potential pitfalls and solutions for use of fluorescent fusion proteins to study
      the lysosome.
AB  - Use of fusion protein tags to investigate lysosomal proteins can be complicated
      by the acidic, protease-rich environment of the lysosome. Potential artifacts
      include degradation or release of the tag and acid quenching of fluorescence.
      Tagging can also affect protein folding, glycosylation and/or trafficking. To
      specifically investigate the use of fluorescent tags to reveal lysosomal
      localization, we tested mCherry derivatives as C-terminal tags for Niemann-Pick
      disease type C protein 2 (NPC2), a luminal lysosomal protein. Full-length mCherry
      was released from the NPC2 chimera while deletion of the 11 N-terminal residues
      of mCherry generated a cleavage-resistant (cr) fluorescent variant. Insertion of
      proline linkers between NPC2 and crmCherry had little effect while Gly-Ser
      linkers promoted cleavage. The NPC2-crmCherry fusion was targeted to the lysosome
      and restored function in NPC2-deficient cells. Fusion of crmCherry to known and
      candidate lysosomal proteins revealed that the linkers had different effects on
      lysosomal localization. Direct fusion of crmCherry impaired mannose 6
      phosphorylation and lysosomal targeting of the lysosomal protease tripeptidyl
      peptidase I (TPP1), while insertion of linkers corrected the defects. Molecular
      modeling suggested structural bases for the effects of different linkers on NPC2
      and TPP1 fusion proteins. While mCherry fusion proteins can be useful tools for
      studying the lysosome and related organelles, our findings underscore the
      potential artifacts associated with such applications. 

PMID- 24586431
TI  - Tissue kallikrein mediates pro-inflammatory pathways and activation of protease
      activated receptor-4 in proximal tubular epithelial cells.
AB  - Tissue kallikrein (KLK1) expression is up-regulated in human diabetic kidney
      tissue and induced by high glucose (HG) in human proximal tubular epithelial
      cells (PTEC). Since the kallikrein-kinin system (KKS) has been linked to cellular
      inflammatory process in many diseases, it is likely that KLK1 expression may
      mediate the inflammatory process during the development of diabetic nephropathy.
      In this study, we explored the role of KLK1 in tubular pro-inflammatory responses
      under the diabetic milieu. Recombinant KLK1 stimulated the production of
      inflammatory cytokines in PTEC via the activation of p42/44 and p38 MAPK
      signaling pathways. Molecular knockdown of endogenous KLK1 expression by siRNA
      transfection in PTEC attenuated advanced glycation end-products (AGE)-induced IL
      8 and ICAM-1 productions in vitro. Interestingly, exposure of PTEC to KLK1
      induced the expression of protease-activated receptors (PARs). There was a 2.9
      fold increase in PAR-4, 1.4-fold increase in PAR-1 and 1.2-fold increase in PAR-2
      mRNA levels. Activation of PAR-4 by a selective agonist was found to elicit the
      pro-inflammatory and pro-fibrotic phenotypes in PTEC while blockade of the
      receptor by specific antagonist attenuated high glucose-induced IL-6, CCL-2, CTGF
      and collagen IV expression. Calcium mobilization by the PAR-4 agonist in PTEC was
      desensitized by pretreatment with KLK1. Consistent with these in vitro findings,
      there was a markedly up-regulation of tubular PAR-4 expression in human diabetic
      renal cortical tissues. Together, these results suggest that up-regulation of
      KLK1 in tubular epithelial cells may mediate pro-inflammatory pathway and PAR
      activation during diabetic nephropathy and provide a new therapeutic target for
      further investigation. 

PMID- 24586432
TI  - Long-term effects of gestational nicotine exposure and food-restriction on gene
      expression in the striatum of adolescent rats.
AB  - Gestational exposure to environmental toxins such as nicotine may result in
      detectable gene expression changes in later life. To investigate the direct toxic
      effects of prenatal nicotine exposure on later brain development, we have used
      transcriptomic analysis of striatal samples to identify gene expression
      differences between adolescent Lister Hooded rats exposed to nicotine in utero
      and controls. Using an additional group of animals matched for the reduced food
      intake experienced in the nicotine group, we were also able to assess the impact
      of imposed food-restriction on gene expression profiles. We found little evidence
      for a role of gestational nicotine exposure on altered gene expression in the
      striatum of adolescent offspring at a significance level of p<0.01 and |log2 fold
      change >0.5|, although we cannot exclude the possibility of nicotine-induced
      changes in other brain regions, or at other time points. We did, however, find
      marked gene expression differences in response to imposed food-restriction. Food
      restriction resulted in significant group differences for a number of immediate
      early genes (IEGs) including Fos, Fosb, Fosl2, Arc, Junb, Nr4a1 and Nr4a3. These
      genes are associated with stress response pathways and therefore may reflect long
      term effects of nutritional deprivation on the development of the stress system. 

PMID- 24586433
TI  - Spatial and temporal pattern of Rift Valley fever outbreaks in Tanzania; 1930 to
      2007.
AB  - BACKGROUND: Rift Valley fever (RVF)-like disease was first reported in Tanzania
      more than eight decades ago and the last large outbreak of the disease occurred
      in 2006-07. This study investigates the spatial and temporal pattern of RVF
      outbreaks in Tanzania over the past 80 years in order to guide prevention and
      control strategies. MATERIALS AND METHODS: A retrospective study was carried out
      based on disease reporting data from Tanzania at district or village level. The
      data were sourced from the Ministries responsible for livestock and human health,
      Tanzania Meteorological Agency and research institutions involved in RVF
      surveillance and diagnosis. The spatial distribution of outbreaks was mapped
      using ArcGIS 10. The space-time permutation model was applied to identify
      clusters of cases, and a multivariable logistic regression model was used to
      identify risk factors associated with the occurrence of outbreaks in the
      district. PRINCIPAL FINDINGS: RVF outbreaks were reported between December and
      June in 1930, 1947, 1957, 1960, 1963, 1968, 1977-79, 1989, 1997-98 and 2006-07 in
      39.2% of the districts in Tanzania. There was statistically significant spatio
      temporal clustering of outbreaks. RVF occurrence was associated with the eastern
      Rift Valley ecosystem (OR = 6.14, CI: 1.96, 19.28), total amount of rainfall of
      >405.4 mm (OR = 12.36, CI: 3.06, 49.88), soil texture (clay [OR = 8.76, CI: 2.52,
      30.50], and loam [OR = 8.79, CI: 2.04, 37.82]). CONCLUSION/SIGNIFICANCE: RVF
      outbreaks were found to be distributed heterogeneously and transmission dynamics
      appeared to vary between areas. The sequence of outbreak waves, continuously
      cover more parts of the country. Whenever infection has been introduced into an
      area, it is likely to be involved in future outbreaks. The cases were more likely
      to be reported from the eastern Rift Valley than from the western Rift Valley
      ecosystem and from areas with clay and loam rather than sandy soil texture.

PMID- 24586434
TI  - Effects of different tillage and straw return on soil organic carbon in a rice
      wheat rotation system.
AB  - Soil management practices, such as tillage method or straw return, could alter
      soil organic carbon (C) contents. However, the effects of tillage method or straw
      return on soil organic C (SOC) have showed inconsistent results in different
      soil/climate/cropping systems. The Yangtze River Delta of China is the main
      production region of rice and wheat, and rice-wheat rotation is the most
      important cropping system in this region. However, few studies in this region
      have been conducted to assess the effects of different tillage methods combined
      with straw return on soil labile C fractions in the rice-wheat rotation system.
      In this study, a field experiment was used to evaluate the effects of different
      tillage methods, straw return and their interaction on soil total organic C (TOC)
      and labile organic C fractions at three soil depths (0-7, 7-14 and 14-21 cm) for
      a rice-wheat rotation in Yangzhong of the Yangtze River Delta of China. Soil TOC,
      easily oxidizable C (EOC), dissolved organic C (DOC) and microbial biomass C
      (MBC) contents were measured in this study. Soil TOC and labile organic C
      fractions contents were significantly affected by straw returns, and were higher
      under straw return treatments than non-straw return at three depths. At 0-7 cm
      depth, soil MBC was significantly higher under plowing tillage than rotary
      tillage, but EOC was just opposite. Rotary tillage had significantly higher soil
      TOC than plowing tillage at 7-14 cm depth. However, at 14-21 cm depth, TOC, DOC
      and MBC were significantly higher under plowing tillage than rotary tillage
      except for EOC. Consequently, under short-term condition, rice and wheat straw
      both return in rice-wheat rotation system could increase SOC content and improve
      soil quality in the Yangtze River Delta. 

PMID- 24586435
TI  - QuickProbs--a fast multiple sequence alignment algorithm designed for graphics
      processors.
AB  - Multiple sequence alignment is a crucial task in a number of biological analyses
      like secondary structure prediction, domain searching, phylogeny, etc. MSAProbs
      is currently the most accurate alignment algorithm, but its effectiveness is
      obtained at the expense of computational time. In the paper we present
      QuickProbs, the variant of MSAProbs customised for graphics processors. We
      selected the two most time consuming stages of MSAProbs to be redesigned for GPU
      execution: the posterior matrices calculation and the consistency transformation.
      Experiments on three popular benchmarks (BAliBASE, PREFAB, OXBench-X) on quad
      core PC equipped with high-end graphics card show QuickProbs to be 5.7 to 9.7
      times faster than original CPU-parallel MSAProbs. Additional tests performed on
      several protein families from Pfam database give overall speed-up of 6.7.
      Compared to other algorithms like MAFFT, MUSCLE, or ClustalW, QuickProbs proved
      to be much more accurate at similar speed. Additionally we introduce a tuned
      variant of QuickProbs which is significantly more accurate on sets of distantly
      related sequences than MSAProbs without exceeding its computation time. The GPU
      part of QuickProbs was implemented in OpenCL, thus the package is suitable for
      graphics processors produced by all major vendors. 

PMID- 24586436
TI  - Evidence towards improved estimation of respiratory muscle effort from diaphragm
      mechanomyographic signals with cardiac vibration interference using sample
      entropy with fixed tolerance values.
AB  - The analysis of amplitude parameters of the diaphragm mechanomyographic (MMGdi)
      signal is a non-invasive technique to assess respiratory muscle effort and to
      detect and quantify the severity of respiratory muscle weakness. The amplitude of
      the MMGdi signal is usually evaluated using the average rectified value or the
      root mean square of the signal. However, these estimations are greatly affected
      by the presence of cardiac vibration or mechanocardiographic (MCG) noise. In this
      study, we present a method for improving the estimation of the respiratory muscle
      effort from MMGdi signals that is robust to the presence of MCG. This method is
      based on the calculation of the sample entropy using fixed tolerance values
      (fSampEn), that is, with tolerance values that are not normalized by the local
      standard deviation of the window analyzed. The behavior of the fSampEn parameter
      was tested in synthesized mechanomyographic signals, with different ratios
      between the amplitude of the MCG and clean mechanomyographic components. As an
      example of application of this technique, the use of fSampEn was explored also in
      recorded MMGdi signals, with different inspiratory loads. The results with both
      synthetic and recorded signals indicate that the entropy parameter is less
      affected by the MCG noise, especially at low signal-to-noise ratios. Therefore,
      we believe that the proposed fSampEn parameter could improve estimates of
      respiratory muscle effort from MMGdi signals with the presence of MCG
      interference. 

PMID- 24586437
TI  - Prognostic value of perineural invasion in gastric cancer: a systematic review
      and meta-analysis.
AB  - BACKGROUND: The prognostic role of perineural invasion in gastric cancer is
      controversial. Here, we present a systemic review and meta-analysis of the
      association between perineural invasion and survival in resectable gastric cancer
      patients. METHODS: A comprehensive literature search for relevant reports
      published up to April 2013 was performed using PubMed, Embase, Web of Science and
      Wanfang Data. Studies that investigated the role of perineural invasion with a
      sample size greater than 100 were included and analyzed. RESULTS: A total of
      30,590 gastric cancer patients who had undergone curative gastrectomy from twenty
      four studies were included. The median rate of perineural invasion positive was
      40.9% (6.8%-75.6%). Fourteen studies investigated overall survival unadjusted for
      other variables in 23,233 gastric cancer patients. The relative hazard estimates
      ranged from 0.568-7.901 with a combined random effects estimate of 2.261 (95% CI
      = 1.841-2.777, P = 0.000). The effect of perineural invasion on overall survival
      adjusted for other prognostic factors was reported in 17 studies incorporating
      8,551 cases. The hazard estimates ranged from 0.420-8.110 with a pooled random
      effects estimates of 1.484 (95% CI = 1.237-1.781, P = 0.000). There was
      heterogeneity between the studies (Q = 49.22, I-squared = 67.5%, P = 0.000).
      Disease-free survival was investigated adjusted in four studies incorporating
      9,083 cases and the pooled fixed hazard ratio estimate was 1.371(95% CI = 1.230
      1.527, P = 0.000). CONCLUSION: Perineural invasion is an independent prognostic
      factor affecting overall survival and disease-free survival of gastric cancer
      patients who had undergone the curative resection. This effect is independent of
      lymph node status, tumor size and the depth of invasion as well as a range of
      other biological variables on multivariate analysis. Large prospective studies
      are now needed to establish perineural invasion as an independent prognostic
      marker for gastric cancer.

PMID- 24586438
TI  - Identification of serum microRNA biomarkers for tuberculosis using RNA-seq.
AB  - Tuberculosis (TB) remains a significant human health issue. More effective
      biomarkers for use in tuberculosis prevention, diagnosis, and treatment,
      including markers that can discriminate between healthy individuals and those
      with latent infection, are urgently needed. To identify a set of such markers, we
      used Solexa sequencing to examine microRNA expression in the serum of patients
      with active disease, healthy individuals with latent TB, and those with or
      without prior BCG inoculation. We identified 24 microRNAs that are up-regulated
      (2.85-1285.93 fold) and 6 microRNAs that are down-regulated (0.003-0.11 fold)
      (P<0.05) in patients with active TB relative to the three groups of healthy
      controls. In addition, 75 microRNAs were up-regulated (2.05-2454.58 fold) and 11
      were down-regulated (0.001-0.42 fold) (P<0.05) in latent-TB infected individuals
      relative to BCG- inoculated individuals. Of interest, 134 microRNAs were
      differentially-expressed in BCG-inoculated relative to un-inoculated individuals
      (18 up-regulated 2.9-499.29 fold, 116 down-regulated 0.0002-0.5 fold), providing
      insights into the effects of BCG inoculation at the microRNA level. Target
      prediction of differentially-expressed microRNAs by microRNA-Gene Network
      analysis and analysis of pathways affected suggest that regulation of the host
      immune system by microRNAs is likely to be one of the main factors in the
      pathogenesis of tuberculosis. qRT-PCR validation indicated that hsa-miR-196b and
      hsa-miR-376c have potential as markers for active TB disease. The microRNA
      differential-expression profiles generated in this study provide a good
      foundation for the development of markers for TB diagnosis, and for
      investigations on the role of microRNAs in BCG-inoculated and latent-infected
      individuals. 

PMID- 24586439
TI  - Mitochondrial respiratory function induces endogenous hypoxia.
AB  - Hypoxia influences many key biological functions. In cancer, it is generally
      believed that hypoxic condition is generated deep inside the tumor because of the
      lack of oxygen supply. However, consumption of oxygen by cancer should be one of
      the key means of regulating oxygen concentration to induce hypoxia but has not
      been well studied. Here, we provide direct evidence of the mitochondrial role in
      the induction of intracellular hypoxia. We used Acetylacetonatobis [2-(2'
      benzothienyl) pyridinato-kN, kC3'] iridium (III) (BTP), a novel oxygen sensor, to
      detect intracellular hypoxia in living cells via microscopy. The well
      differentiated cancer cell lines, LNCaP and MCF-7, showed intracellular hypoxia
      without exogenous hypoxia in an open environment. This may be caused by high
      oxygen consumption, low oxygen diffusion in water, and low oxygen incorporation
      to the cells. In contrast, the poorly-differentiated cancer cell lines: PC-3 and
      MDAMB231 exhibited intracellular normoxia by low oxygen consumption. The specific
      complex I inhibitor, rotenone, and the reduction of mitochondrial DNA (mtDNA)
      content reduced intracellular hypoxia, indicating that intracellular oxygen
      concentration is regulated by the consumption of oxygen by mitochondria. HIF
      1alpha was activated in endogenously hypoxic LNCaP and the activation was
      dependent on mitochondrial respiratory function. Intracellular hypoxic status is
      regulated by glucose by parabolic dose response. The low concentration of glucose
      (0.045 mg/ml) induced strongest intracellular hypoxia possibly because of the
      Crabtree effect. Addition of FCS to the media induced intracellular hypoxia in
      LNCaP, and this effect was partially mimicked by an androgen analog, R1881, and
      inhibited by the anti-androgen, flutamide. These results indicate that
      mitochondrial respiratory function determines intracellular hypoxic status and
      may regulate oxygen-dependent biological functions. 

PMID- 24586441
TI  - The rise and fall of plankton: long-term changes in the vertical distribution of
      algae and grazers in Lake Baikal, Siberia.
AB  - Both surface water temperatures and the intensity of thermal stratification have
      increased recently in large lakes throughout the world. Such physical changes can
      be accompanied by shifts in plankton community structure, including changes in
      relative abundances and depth distributions. Here we analyzed 45 years of data
      from Lake Baikal, the world's oldest, deepest, and most voluminous lake, to
      assess long-term trends in the depth distribution of pelagic phytoplankton and
      zooplankton. Surface water temperatures in Lake Baikal increased steadily between
      1955 and 2000, resulting in a stronger thermal gradient within the top 50 m of
      the water column. In conjunction with these physical changes our analyses reveal
      significant shifts in the daytime depth distribution of important phytoplankton
      and zooplankton groups. The relatively heavy diatoms, which often rely on mixing
      to remain suspended in the photic zone, shifted downward in the water column by
      1.90 m y(-1), while the depths of other phytoplankton groups did not change
      significantly. Over the same time span the density-weighted average depth of most
      major zooplankton groups, including cladocerans, rotifers, and immature copepods,
      exhibited rapid shifts toward shallower positions (0.57-0.75 m y(-1)). As a
      result of these depth changes the vertical overlap between herbivorous copepods
      (Epischura baikalensis) and their algal food appears to have increased through
      time while that for cladocerans decreased. We hypothesize that warming surface
      waters and reduced mixing caused these ecological changes. Future studies should
      examine how changes in the vertical distribution of plankton might impact energy
      flow in this lake and others. 

PMID- 24586440
TI  - Toward a semi-self-paced EEG brain computer interface: decoding initiation state
      from non-initiation state in dedicated time slots.
AB  - Brain computer interfaces (BCIs) offer a broad class of neurologically impaired
      individuals an alternative means to interact with the environment. Many BCIs are
      "synchronous" systems, in which the system sets the timing of the interaction and
      tries to infer what control command the subject is issuing at each prompting. In
      contrast, in "asynchronous" BCIs subjects pace the interaction and the system
      must determine when the subject's control command occurs. In this paper we
      propose a new idea for BCI which draws upon the strengths of both approaches. The
      subjects are externally paced and the BCI is able to determine when control
      commands are issued by decoding the subject's intention for initiating control in
      dedicated time slots. A single task with randomly interleaved trials was designed
      to test whether it can be used as stimulus for inducing initiation and non
      initiation states when the sensory and motor requirements for the two types of
      trials are very nearly identical. Further, the essential problem on the
      discrimination between initiation state and non-initiation state was studied. We
      tested the ability of EEG spectral power to distinguish between these two states.
      Among the four standard EEG frequency bands, beta band power recorded over
      parietal-occipital cortices provided the best performance, achieving an average
      accuracy of 86% for the correct classification of initiation and non-initiation
      states. Moreover, delta band power recorded over parietal and motor areas yielded
      a good performance and thus could also be used as an alternative feature to
      discriminate these two mental states. The results demonstrate the viability of
      our proposed idea for a BCI design based on conventional EEG features. Our
      proposal offers the potential to mitigate the signal detection challenges of
      fully asynchronous BCIs, while providing greater flexibility to the subject than
      traditional synchronous BCIs. 

PMID- 24586442
TI  - Extremely low frequency magnetic field (50 Hz, 0.5 mT) reduces oxidative stress
      in the brain of gerbils submitted to global cerebral ischemia.
AB  - Magnetic field as ecological factor has influence on all living beings. The aim
      of this study was to determine if extremely low frequency magnetic field (ELF-MF,
      50 Hz, 0.5 mT) affects oxidative stress in the brain of gerbils submitted to 10
      min global cerebral ischemia. After occlusion of both carotid arteries, 3-month
      old gerbils were continuously exposed to ELF-MF for 7 days. Nitric oxide and
      superoxide anion production, superoxide dismutase activity and index of lipid
      peroxidation were examined in the forebrain cortex, striatum and hippocampus on
      the 7(th) (immediate effect of ELF-MF) and 14(th) day after reperfusion (delayed
      effect of ELF-MF). Ischemia per se increased oxidative stress in the brain on the
      7(th) and 14(th) day after reperfusion. ELF-MF also increased oxidative stress,
      but to a greater extent than ischemia, only immediately after cessation of
      exposure. Ischemic gerbils exposed to ELF-MF had increased oxidative stress
      parameters on the 7(th) day after reperfusion, but to a lesser extent than
      ischemic or ELF-MF-exposed animals. On the 14(th) day after reperfusion,
      oxidative stress parameters in the brain of these gerbils were mostly at the
      control levels. Applied ELF-MF decreases oxidative stress induced by global
      cerebral ischemia and thereby reduces possible negative consequences which free
      radical species could have in the brain. The results presented here indicate a
      beneficial effect of ELF-MF (50 Hz, 0.5 mT) in the model of global cerebral
      ischemia. 

PMID- 24586443
TI  - S100A9 knockout decreases the memory impairment and neuropathology in crossbreed
      mice of Tg2576 and S100A9 knockout mice model.
AB  - Our previous study presented evidence that the inflammation-related S100A9 gene
      is significantly upregulated in the brains of Alzheimer's disease (AD) animal
      models and human AD patients. In addition, experiments have shown that knockdown
      of S100A9 expression improves cognition function in AD model mice (Tg2576), and
      these animals exhibit reduced amyloid plaque burden. In this study, we
      established a new transgenic animal model of AD by crossbreeding the Tg2576 mouse
      with the S100A9 knockout (KO) mouse. We observed that S100A9KO/Tg2576 (KO/Tg)
      mice displayed an increased spatial reference memory in the Morris water maze
      task and Y-maze task as well as decreased amyloid beta peptide (Abeta)
      neuropathology because of reduced levels of Abeta, C-terminal fragments of
      amyloid precursor protein (APP-CT) and phosphorylated tau and increased
      expression of anti-inflammatory IL-10 and also decreased expression of
      inflammatory IL-6 and tumor neurosis factor (TNF)-alpha when compared with age
      matched S100A9WT/Tg2576 (WT/Tg) mice. Overall, these results suggest that S100A9
      is responsible for the neurodegeneration and cognitive deficits in Tg2576 mice.
      The mechanism of S100A9 is able to coincide with the inflammatory process. These
      findings indicate that knockout of S100A9 is a potential target for the
      pharmacological therapy of AD. 

PMID- 24586444
TI  - The clinical features of infantile hypertrophic pyloric stenosis in Chinese Han
      population: analysis from 1998 to 2010.
AB  - OBJECTIVE: To investigate clinical features of infantile hypertrophic pyloric
      stenosis (IHPS) in Chinese Han population. METHODS: Three hundred and sixteen
      hospitalized patients with IHPS from January 1998 to February 2010 were
      retrospectively reviewed, and data including patient's sex, onset age, other
      coexisting congenital defects, pyloric circular muscle thickness evaluated by
      ultrasonograph, serum electrolytes concentration, and results of arterial blood
      gas analysis on admission were collected. The patients were divided into two
      groups: the duration between first onset and admission less than or equal to 10
      days (early onset group), and more than 10 days (late onset group). The results
      of arterial blood gas and serum electrolyte concentration were compared between
      the two groups. RESULTS: There were 271 males and 45 females in 316 patients; the
      onset age ranged between 1 and 351 (26.5+/-26.6) days. The birth weight ranged
      between 1.6 and 4.5 (3.23+/-0.44) kilograms; coexisting congenital defects were
      found in 65 cases (20.6%). Pyloric circular muscle thickness was 4-8 (5.4+/-1.0)
      millimetres (mm). For the early onset group, the rates of hypokalemia,
      hypochloraemia and hypercapnia were significantly lower than those in the late
      onset group (18.67% VS 50%, P<0.0001; 46.03% VS 71.01%, P = 0.003; 56.58% VS
      83.44%, P = 2.17*10(-5); respectively). CONCLUSIONS: The symptom duration in
      Chinese Han population was longer than that in other populations. And as the
      prolongation of symptom duration, the incidence of acid-base imbalance increased
      significantly. Infants with persistent vomiting at the age of 3~5 weeks after
      birth should be considered IHPS, and go to hospital as soon as possible in order
      to reduce the incidence of hypokalemia, hypochloraemia and hypercapnia, and avoid
      deterioration.

PMID- 24586445
TI  - The pandemic influenza A (H1N1) 2009 vaccine does not increase the mortality rate
      of idiopathic interstitial pneumonia: a matched case-control study.
AB  - BACKGROUND: Evidence regarding the mortality rate after administration of the
      pandemic influenza A (H1N1) 2009 vaccine on patients with underlying diseases is
      currently scarce. We conducted a case-control study in Japan to compare the
      mortality rates of patients with idiopathic interstitial pneumonia after the
      vaccines were administered and were not administered. METHODS: Between October
      2009 and March 2010, we collected clinical records in Japan and conducted a 1:1
      matched case-control study. Patients with idiopathic interstitial pneumonia who
      died during this period were considered case patients, and those who survived
      were considered control patients. We determined and compared the proportion of
      each group that received the pandemic influenza A (H1N1) 2009 vaccine and
      estimated the odds ratio. Finally, we conducted simulations that compensated for
      the shortcomings of the study associated with adjusted severity of idiopathic
      interstitial pneumonia. RESULTS: The case and control groups each comprised of 75
      patients with idiopathic interstitial pneumonia. The proportion of patients who
      received the pandemic influenza A (H1N1) 2009 vaccine was 30.7% and 38.7% for the
      case and control groups, respectively. During that winter, the crude conditional
      odds ratio of mortality was 0.63 (95% confidence interval, 0.25-1.47) and the
      adjusted conditional odds ratio was 1.18 (95% confidence interval, 0.33-4.49);
      neither was significant. The simulation study showed more accurate conditional
      odds ratios of 0.63-0.71. CONCLUSIONS: In our study, we detected no evidence that
      the influenza A (H1N1) 2009 vaccine increased the mortality rate of patients with
      idiopathic interstitial pneumonia. The results, however, are limited by the small
      sample size and low statistical power. A larger-scale study is required.

PMID- 24586446
TI  - Myc and max genome-wide binding sites analysis links the Myc regulatory network
      with the polycomb and the core pluripotency networks in mouse embryonic stem
      cells.
AB  - Myc is a master transcription factor that has been demonstrated to be required
      for embryonic stem cell (ESC) pluripotency, self-renewal, and inhibition of
      differentiation. Although recent works have identified several Myc-targets in
      ESCs, the list of Myc binding sites is largely incomplete due to the low
      sensitivity and specificity of the antibodies available. To systematically
      identify Myc binding sites in mouse ESCs, we used a stringent streptavidin-based
      genome-wide chromatin immunoprecipitation (ChIP-Seq) approach with biotin-tagged
      Myc (Bio-Myc) as well as a ChIP-Seq of the Myc binding partner Max. This analysis
      identified 4325 Myc binding sites, of which 2885 were newly identified. The
      identified sites overlap with more than 85% of the Max binding sites and are
      enriched for H3K4me3-positive promoters and active enhancers. Remarkably, this
      analysis unveils that Myc/Max regulates chromatin modifiers and transcriptional
      regulators involved in stem cell self-renewal linking the Myc-centered network
      with the Polycomb and the Core networks. These results provide insights into the
      contribution of Myc and Max in maintaining stem cell self-renewal and keeping
      these cells in an undifferentiated state. 

PMID- 24586447
TI  - Diagnosis of whooping cough in Switzerland: differentiating Bordetella pertussis
      from Bordetella holmesii by polymerase chain reaction.
AB  - Bordetella holmesii, an emerging pathogen, can be misidentified as Bordetella
      pertussis by routine polymerase chain reaction (PCR). In some reports, up to 29%
      of the patients diagnosed with pertussis have in fact B. holmesii infection and
      invasive, non-respiratory B. holmesii infections have been reported worldwide.
      This misdiagnosis undermines the knowledge of pertussis' epidemiology, and may
      lead to misconceptions on pertussis vaccine's efficacy. Recently, the number of
      whooping cough cases has increased significantly in several countries. The aim of
      this retrospective study was to determine whether B. holmesii was contributing to
      the increase in laboratory-confirmed cases of B. pertussis in Switzerland. A
      multiplex species-specific quantitative PCR assay was performed on 196
      nasopharyngeal samples from Swiss patients with PCR-confirmed Bordetella
      infection (median age: 6 years-old, minimum 21 days-old, maximum 86 years-old),
      formerly diagnosed as Bordetella pertussis (IS481+). No B. holmesii (IS481+,
      IS1001-, hIS1001+) was identified. We discuss whether laboratories should
      implement specific PCR to recognize different Bordetella species. We conclude
      that in Switzerland B. holmesii seems to be circulating less than in neighboring
      countries and that specific diagnostic procedures are not necessary routinely.
      However, as the epidemiological situation may change rapidly, periodic
      reevaluation is suggested. 

PMID- 24586448
TI  - Node interference and robustness: performing virtual knock-out experiments on
      biological networks: the case of leukocyte integrin activation network.
AB  - The increasing availability of large network datasets derived from high
      throughput experiments requires the development of tools to extract relevant
      information from biological networks, and the development of computational
      methods capable of detecting qualitative and quantitative changes in the
      topological properties of biological networks is of critical relevance. We
      introduce the notions of node interference and robustness as measures of the
      reciprocal influence between nodes within a network. We examine the theoretical
      significance of these new, centrality-based, measures by characterizing the
      topological relationships between nodes and groups of nodes. Node interference
      analysis allows topologically determining the context of functional influence of
      single nodes. Conversely, the node robustness analysis allows topologically
      identifying the nodes having the highest functional influence on a specific node.
      A new Cytoscape plug-in calculating these measures was developed and applied to a
      protein-protein interaction network specifically regulating integrin activation
      in human primary leukocytes. Notably, the functional effects of compounds
      inhibiting important protein kinases, such as SRC, HCK, FGR and JAK2, are
      predicted by the interference and robustness analysis, are in agreement with
      previous studies and are confirmed by laboratory experiments. The interference
      and robustness notions can be applied to a variety of different contexts,
      including, for instance, the identification of potential side effects of drugs or
      the characterization of the consequences of genes deletion, duplication or of
      proteins degradation, opening new perspectives in biological network analysis.

PMID- 24586449
TI  - An evaluation framework and comparative analysis of the widely used first
      programming languages.
AB  - Computer programming is the core of computer science curriculum. Several
      programming languages have been used to teach the first course in computer
      programming, and such languages are referred to as first programming language
      (FPL). The pool of programming languages has been evolving with the development
      of new languages, and from this pool different languages have been used as FPL at
      different times. Though the selection of an appropriate FPL is very important,
      yet it has been a controversial issue in the presence of many choices. Many
      efforts have been made for designing a good FPL, however, there is no ample way
      to evaluate and compare the existing languages so as to find the most suitable
      FPL. In this article, we have proposed a framework to evaluate the existing
      imperative, and object oriented languages for their suitability as an appropriate
      FPL. Furthermore, based on the proposed framework we have devised a customizable
      scoring function to compute a quantitative suitability score for a language,
      which reflects its conformance to the proposed framework. Lastly, we have also
      evaluated the conformance of the widely used FPLs to the proposed framework, and
      have also computed their suitability scores. 

PMID- 24586450
TI  - Inferring domain-domain interactions from protein-protein interactions with
      formal concept analysis.
AB  - Identifying reliable domain-domain interactions will increase our ability to
      predict novel protein-protein interactions, to unravel interactions in protein
      complexes, and thus gain more information about the function and behavior of
      genes. One of the challenges of identifying reliable domain-domain interactions
      is domain promiscuity. Promiscuous domains are domains that can occur in many
      domain architectures and are therefore found in many proteins. This becomes a
      problem for a method where the score of a domain-pair is the ratio between
      observed and expected frequencies because the protein-protein interaction network
      is sparse. As such, many protein-pairs will be non-interacting and domain-pairs
      with promiscuous domains will be penalized. This domain promiscuity challenge to
      the problem of inferring reliable domain-domain interactions from protein-protein
      interactions has been recognized, and a number of work-arounds have been
      proposed. This paper reports on an application of Formal Concept Analysis to this
      problem. It is found that the relationship between formal concepts provides a
      natural way for rare domains to elevate the rank of promiscuous domain-pairs and
      enrich highly ranked domain-pairs with reliable domain-domain interactions. This
      piggybacking of promiscuous domain-pairs onto less promiscuous domain-pairs is
      possible only with concept lattices whose attribute-labels are not reduced and is
      enhanced by the presence of proteins that comprise both promiscuous and rare
      domains. 

PMID- 24586451
TI  - Prioritizing populations for conservation using phylogenetic networks.
AB  - In the face of inevitable future losses to biodiversity, ranking species by
      conservation priority seems more than prudent. Setting conservation priorities
      within species (i.e., at the population level) may be critical as species ranges
      become fragmented and connectivity declines. However, existing approaches to
      prioritization (e.g., scoring organisms by their expected genetic contribution)
      are based on phylogenetic trees, which may be poor representations of
      differentiation below the species level. In this paper we extend evolutionary
      isolation indices used in conservation planning from phylogenetic trees to
      phylogenetic networks. Such networks better represent population differentiation,
      and our extension allows populations to be ranked in order of their expected
      contribution to the set. We illustrate the approach using data from two imperiled
      species: the spotted owl Strix occidentalis in North America and the mountain
      pygmy-possum Burramys parvus in Australia. Using previously published
      mitochondrial and microsatellite data, we construct phylogenetic networks and
      score each population by its relative genetic distinctiveness. In both cases, our
      phylogenetic networks capture the geographic structure of each species:
      geographically peripheral populations harbor less-redundant genetic information,
      increasing their conservation rankings. We note that our approach can be used
      with all conservation-relevant distances (e.g., those based on whole-genome,
      ecological, or adaptive variation) and suggest it be added to the assortment of
      tools available to wildlife managers for allocating effort among threatened
      populations. 

PMID- 24586452
TI  - Genomic survey, gene expression analysis and structural modeling suggest diverse
      roles of DNA methyltransferases in legumes.
AB  - DNA methylation plays a crucial role in development through inheritable gene
      silencing. Plants possess three types of DNA methyltransferases (MTases), namely
      Methyltransferase (MET), Chromomethylase (CMT) and Domains Rearranged
      Methyltransferase (DRM), which maintain methylation at CG, CHG and CHH sites. DNA
      MTases have not been studied in legumes so far. Here, we report the
      identification and analysis of putative DNA MTases in five legumes, including
      chickpea, soybean, pigeonpea, Medicago and Lotus. MTases in legumes could be
      classified in known MET, CMT, DRM and DNA nucleotide methyltransferases (DNMT2)
      subfamilies based on their domain organization. First three MTases represent DNA
      MTases, whereas DNMT2 represents a transfer RNA (tRNA) MTase. Structural
      comparison of all the MTases in plants with known MTases in mammalian and plant
      systems have been reported to assign structural features in context of biological
      functions of these proteins. The structure analysis clearly specified regions
      crucial for protein-protein interactions and regions important for nucleosome
      binding in various domains of CMT and MET proteins. In addition, structural model
      of DRM suggested that circular permutation of motifs does not have any effect on
      overall structure of DNA methyltransferase domain. These results provide valuable
      insights into role of various domains in molecular recognition and should
      facilitate mechanistic understanding of their function in mediating specific
      methylation patterns. Further, the comprehensive gene expression analyses of
      MTases in legumes provided evidence of their role in various developmental
      processes throughout the plant life cycle and response to various abiotic
      stresses. Overall, our study will be very helpful in establishing the specific
      functions of DNA MTases in legumes. 

PMID- 24586453
TI  - The activated SA and JA signaling pathways have an influence on flg22-triggered
      oxidative burst and callose deposition.
AB  - The first line of defense in plants against pathogens is induced by the
      recognition of microbe-associated molecular patterns (MAMP). Perception of
      bacterial flagellin (flg22) by the pattern recognition receptor flagellin-sensing
      2 (FLS2) is the best characterized MAMP response, although the underlying
      molecular mechanisms are not fully understood. Here we studied the relationship
      between salicylic acid (SA) or jasmonic acid (JA) signaling and FLS2-mediated
      signaling by monitoring flg22-triggered responses in known SA or JA related
      mutants of Arabidopsis thaliana (L.) Heynh. The sid2 mutant, impaired in SA
      biosynthesis, had less basal FLS2 mRNA accumulation than the wild type, which
      correlated with suppression of early flg22 responses such as ROS production and
      induction of marker genes, WRKY29 and FRK1. The JA-signaling mutants, jar1 and
      coi1, exhibited an enhanced flg22-triggered oxidative burst and more callose
      accumulation than the wild type, and pretreatment with SA or coronatine (COR), a
      structural mimic of JA-isoleucine, altered these flg22-induced responses.
      Nonexpressor of pathogenesis-related genes 1 (NPR1) acted downstream of SID2 and
      required SA-dependent priming for the enhanced flg22-triggered oxidative burst
      and callose deposition. Activation of JA signaling by COR pretreatment suppressed
      the flg22-triggered oxidative burst and callose accumulation in a coronatine
      insensitive 1 (COI1) dependent manner. COR had a negative effect on flg22
      responses but only the flg22-triggered oxidative burst depended on SA-JA/COR
      signaling antagonism. Thus the activated SA and JA signaling pathways have an
      influence on flg22-triggered oxidative burst and callose deposition. These
      results may explain how SA and JA signaling are cross talked for regulation of
      flg22-triggered responses. 

PMID- 24586454
TI  - Monocyte chemotactic protein 1 (MCP-1) modulates pro-survival signaling to
      promote progression of head and neck squamous cell carcinoma.
AB  - BACKGROUND: Monocyte chemotactic protein-1 (MCP-1) recruits monocytes and
      macrophages to inflammation sites, and inflammatory infiltration correlates with
      the progression of head and neck squamous cell carcinoma (HNSCC). This study aims
      to determine whether MCP-1 expression is related to HNSCC malignancy and patient
      survival. We also investigated the relationship between MCP-1 expression and the
      phosphorylation state of the pro-survival pathway factors Akt, ERK, and STAT3.
      METHODS: Expression of MCP-1 and related proteins in HNSCC cell lines was
      investigated using western blotting. HNSCC patients (34) without distant
      metastasis at diagnosis were recruited for tissue specimen evaluation of MCP-1
      expression and clinical outcomes. The relationship between MCP-1 expression and
      survival was evaluated using the Cox proportional hazard model with stepwise
      selection. RESULTS: High-grade HNSCC cell lines were found to have higher levels
      of active Akt, ERK, and/or STAT3 than did lower grade cell lines under serum-free
      condition. OCSL, the most malignant cell line, had the highest level of
      endogenous MCP-1. Administration of exogenous recombinant MCP-1 increased
      phosphorylation of Akt, ERK, and STAT3 in a dose- and time-dependent manner and
      increased cellular resistance to serum starvation. Inhibition of Akt, ERK, or
      STAT3 reduced cell growth and caused cell death. Long-term survival of HNSCC
      patients was negatively associated with the histological intensity of MCP-1,
      implicating MCP-1 as a potential prognostic marker for HNSCC. CONCLUSIONS: These
      results suggest that overexpressed MCP-1 in cancer cells may promote HNSCC
      progression through upregulating pro-survival signaling pathways. High cellular
      MCP-1 expression is related to poor overall survival rate in HNSCC patients.

PMID- 24586455
TI  - Lymphatic involvement in the disappearance of steroidogenic cells from the corpus
      luteum during luteolysis.
AB  - In mammals, the corpus luteum (CL) is an essential endocrine gland for the
      establishment and maintenance of pregnancy. If pregnancy is not established, the
      CL regresses and disappears rapidly from the ovary. A possible explanation for
      the rapid disappearance of the CL is that luteal cells are transported from the
      ovary via lymphatic vessels. Here, we report the presence of cells positive for
      3beta-hydroxysteroid dehydrogenase (3beta-HSD), an enzyme involved in
      progesterone synthesis, in the lumen of lymphatic vessels at the regressing
      luteal stage and in the lymphatic fluid collected from the ovarian pedicle
      ipsilateral to the regressing CL. The 3beta-HSD positive cells were alive and
      contained lipid droplets. The 3beta-HSD positive cells in the lymphatic fluid
      were most abundant at days 22-24 after ovulation. These findings show that live
      steroidogenic cells are in the lymphatic vessels drained from the CL. The outflow
      of steroidogenic cells starts at the regressing luteal stage and continues after
      next ovulation. The overall findings suggest that the complete disappearance of
      the CL during luteolysis is involved in the outflow of luteal cells from the CL
      via ovarian lymphatic vessels. 

PMID- 24586456
TI  - Description and phylogeny of Tetrakeronopsis silvanetoi gen. nov., sp. nov.
      (Hypotricha, Pseudokeronopsidae), a new benthic marine ciliate from Brazil.
AB  - Pseudokeronopsidae Borror & Wicklow, 1983 are biotechnologically important
      ciliate protists which produce toxic defense substances; however, their diversity
      is still little known in Brazil. In the present study, Tetrakeronopsis
      silvanetoi, a new genus and species of marine pseudokeronopsid hypotrichs is
      described from samples of water with bottom sediment collected from the coast of
      Sao Paulo state. Its phylogenetic affinities to the "core urostyloids" are
      hypothesized based on analyses of the 18S-rDNA marker, and a new subfamily, the
      Nothoholostichinae subfam. nov., is erected to name the monophylum composed of
      pseudokeronopsids in which the anterior corona is usually formed by four frontal
      cirri. In addition, the new combination Monocoronella longissima comb. nov. is
      proposed for Nothoholosticha longissima (Dragesco & Dragesco-Kerneis, 1986) Li et
      al., 2009. 

PMID- 24586457
TI  - Diabetic nephropathy and its risk factors in a society with a type 2 diabetes
      epidemic: a Saudi National Diabetes Registry-based study.
AB  - AIMS: The prevalence of diabetic nephropathy and its risk factors have not been
      studied in a society known to have diabetes epidemic like Saudi Arabia. Using a
      large data base registry will provide a better understanding and accurate
      assessment of this chronic complication and its related risk factors.
      METHODOLOGY: A total of 54,670 patients with type 2 diabetes aged >= 25 years
      were selected from the Saudi National Diabetes Registry (SNDR) and analyzed for
      the presence of diabetic nephropathy. The American Diabetes Association (ADA)
      criterion was used to identify cases with microalbuminuria, macroalbuminuria and
      end stage renal disease (ESRD) for prevalence estimation and risk factor
      assessment. RESULTS: The overall prevalence of diabetic nephropathy was 10.8%,
      divided into 1.2% microalbuminuria, 8.1%macroalbuninuria and 1.5% ESRD. Age and
      diabetes duration as important risk factors have a strong impact on the
      prevalence of diabetic nephropathy, ranging from 3.7% in patients aged 25-44
      years and a duration of >5 years, to 21.8% in patients >= 65 years with a
      diabetes duration of >= 15 years. Diabetes duration, retinopathy, neuropathy,
      hypertension, age >45 years, hyperlipidemia, male gender, smoking, and
      chronologically, poor glycemic control has a significantly high risk for diabetic
      nephropathy. CONCLUSION: The prevalence of diabetic nephropathy is underestimated
      as a result of a shortage of screening programs. Risk factors related to diabetic
      nephropathy in this society are similar to other societies. There is thus an
      urgent need for screening and prevention programs for diabetic nephropathy among
      the Saudi population.

PMID- 24586458
TI  - Semiquantitative analysis of clinical heat stress in Clostridium difficile strain
      630 using a GeLC/MS workflow with emPAI quantitation.
AB  - Clostridium difficile is considered to be the most frequent cause of infectious
      bacterial diarrhoea in hospitals worldwide yet its adaptive ability remains
      relatively uncharacterised. Here, we used GeLC/MS and the exponentially modified
      protein abundance index (emPAI) calculation to determine proteomic changes in
      response to a clinically relevant heat stress. Reproducibility between both
      biological and technical replicates was good, and a 37 degrees C proteome of 224
      proteins was complemented by a 41 degrees C proteome of 202 proteins at a 1%
      false discovery rate. Overall, 236 C. difficile proteins were identified and
      functionally categorised, of which 178 were available for comparative purposes. A
      total of 65 proteins (37%) were modulated by 1.5-fold or more at 41 degrees C
      compared to 37 degrees C and we noted changes in the majority of proteins
      associated with amino acid metabolism, including upregulation of the reductive
      branch of the leucine fermentation pathway. Motility was reduced at 41 degrees C
      as evidenced by a 2.7 fold decrease in the flagellar filament protein, FliC, and
      a global increase in proteins associated with detoxification and adaptation to
      atypical conditions was observed, concomitant with decreases in proteins
      mediating transcriptional elongation and the initiation of protein synthesis.
      Trigger factor was down regulated by almost 5-fold. We propose that under heat
      stress, titration of the GroESL and dnaJK/grpE chaperones by misfolded proteins
      will, in the absence of trigger factor, prevent nascent chains from emerging
      efficiently from the ribosome causing translational stalling and also an increase
      in secretion. The current work has thus allowed development of a heat stress
      model for the key cellular processes of protein folding and export. 

PMID- 24586459
TI  - Xenoestrogens alter estrogen receptor (ER) alpha intracellular levels.
AB  - 17beta-estradiol (E2)-dependent estrogen receptor (ER) alpha intracellular
      concentration is a well recognized critical step in the pleiotropic effects
      elicited by E2 in several target tissues. Beside E2, a class of synthetic and
      plant-derived chemicals collectively named endocrine disruptors (EDs) or
      xenoestrogens bind to and modify both nuclear and extra-nuclear ERalpha
      activities. However, at the present no information is available on the ability of
      EDs to hamper ERalpha intracellular concentration. Here, the effects of bisphenol
      A (BPA) and naringenin (Nar), prototypes of synthetic and plant-derived ERalpha
      ligands, have been evaluated on ERalpha levels in MCF-7 cells. Both EDs mimic E2
      in triggering ERalpha Ser118 phosphorylation and gene transcription. However,
      only E2 or BPA induce an increase of cell proliferation; whereas 24 hrs after Nar
      stimulation a dose-dependent decrease in cell number is reported. E2 or BPA
      treatment reduces ERalpha protein and mRNA levels after 24 hrs. Contrarily, Nar
      stimulation does not alter ERalpha content but reduces ERalpha mRNA levels like
      other ligands. Co-stimulation experiments indicate that 48 hrs of Nar treatment
      prevents the E2-induced ERalpha degradation and hijacks the physiological ability
      of E2:ERalpha complex to regulate gene transcription. Mechanistically, Nar
      induces ERalpha protein accumulation by preventing proteasomal receptor
      degradation via persistent activation of p38/MAPK pathway. As a whole these data
      demonstrate that ERalpha intracellular concentration is an important target
      through which EDs hamper the hormonal milieu of E2 target cells driving cells to
      different outcomes or mimicking E2 even in the absence of the hormone.

PMID- 24586460
TI  - Synaptic elements for GABAergic feed-forward signaling between HII horizontal
      cells and blue cone bipolar cells are enriched beneath primate S-cones.
AB  - The functional roles and synaptic features of horizontal cells in the mammalian
      retina are still controversial. Evidence exists for feedback signaling from
      horizontal cells to cones and feed-forward signaling from horizontal cells to
      bipolar cells, but the details of the latter remain elusive. Here,
      immunohistochemistry and confocal microscopy were used to analyze the expression
      patterns of the SNARE protein syntaxin-4, the GABA receptor subunits alpha1 and
      rho, and the cation-chloride cotransporters NKCC and KCC2 in the outer plexiform
      layer of primate retina. In macaque retina, as observed previously in other
      species, syntaxin-4 was expressed on dendrites and axon terminals of horizontal
      cells at cone pedicles and rod spherules. At cones, syntaxin-4 appeared densely
      clustered in two bands, at horizontal cell dendritic tips and at the level of
      desmosome-like junctions. Interestingly, in the lower band where horizontal cells
      may synapse directly onto bipolar cells, syntaxin-4 was highly enriched beneath
      short-wavelength sensitive (S) cones and colocalized with calbindin, a marker for
      HII horizontal cells. The enrichment at S-cones was not observed in either mouse
      or ground squirrel. Furthermore, high amounts of both GABA receptor and cation
      chloride cotransporter subunits were found beneath primate S-cones. Finally,
      while syntaxin-4 was expressed by both HI and HII horizontal cell types, the
      intense clustering and colocalization with calbindin at S-cones indicated an
      enhanced expression in HII cells. Taken together, GABA receptors beneath cone
      pedicles, chloride transporters, and syntaxin-4 are putative constituents of a
      synaptic set of proteins which would be required for a GABA-mediated feed-forward
      pathway via horizontal cells carrying signals directly from cones to bipolar
      cells. 

PMID- 24586461
TI  - Improvement of chloride transport defect by gonadotropin-releasing hormone (GnRH)
      in cystic fibrosis epithelial cells.
AB  - Cystic fibrosis (CF), the most common autosomal recessive disease in Caucasians,
      is due to mutations in the CFTR gene. F508del, the most frequent mutation in
      patients, impairs CFTR protein folding and biosynthesis. The F508del-CFTR protein
      is retained in the endoplasmic reticulum (ER) and its traffic to the plasma
      membrane is altered. Nevertheless, if it reaches the cell surface, it exhibits a
      Cl(-) channel function despite a short half-life. Pharmacological treatments may
      target the F508del-CFTR defect directly by binding to the mutant protein or
      indirectly by altering cellular proteostasis, and promote its plasma membrane
      targeting and stability. We previously showed that annexine A5 (AnxA5) directly
      binds to F508del-CFTR and, when overexpressed, promotes its membrane stability,
      leading to the restoration of some Cl(-) channel function in cells. Because
      Gonadotropin-Releasing Hormone (GnRH) increases AnxA5 expression in some cells,
      we tested it in CF cells. We showed that human epithelial cells express GnRH
      receptors (GnRH-R) and that GnRH induces an AnxA5 overexpression and an increased
      Cl(-) channel function in F508del-CFTR cells, due to an increased stability of
      the protein in the membranes. Beside the numerous physiological implications of
      the GnRH-R expression in epithelial cells, we propose that a topical use of GnRH
      is a potential treatment in CF. 

PMID- 24586462
TI  - CMTM3 inhibits human testicular cancer cell growth through inducing cell-cycle
      arrest and apoptosis.
AB  - Human CMTM3 has been proposed as a putative tumor suppressor gene. The loss of
      CMTM3 has been found in several carcinomas. However, the regulation of CMTM3
      expression and its function in tumor progression remain largely unknown. Here, we
      investigated the regulation of CMTM3 expression, function and molecular mechanism
      in human testicular cancer cells. CMTM3 was frequently downregulated or silenced
      in testicular cancer cell lines and tumor tissues but highly expressed in normal
      testis tissues. The re-expression of CMTM3 significantly suppressed the colony
      formation, proliferation, and migration capacity of testicular cancer cells by
      inducing a G2 cell cycle arrest and apoptosis. Moreover, the re-expression of
      CMTM3 activated the transcription of p53, induced p53 accumulation, up-regulated
      the expression of p21, and increased the cleavage of caspase 9, 8, 3, and PARP.
      The downregulation of CMTM3 in clinical tumor tissues was associated with the
      methylation of a single CpG site located within the Sp1/Sp3-responsive region of
      the core promoter. These results indicate that CMTM3 can function as tumor
      suppressor through the induction of a G2 cell cycle arrest and apoptosis. CMTM3
      is thus involved in testicular cancer pathogenesis, and it is frequently at least
      partially silenced by the methylation of a single, specific CpG site in tumor
      tissues. 

PMID- 24586463
TI  - Acute lymphoid leukemia cells with greater stem cell antigen-1 (Ly6a/Sca-1)
      expression exhibit higher levels of metalloproteinase activity and are more
      aggressive in vivo.
AB  - Stem cell antigen-1 (Ly6a/Sca-1) is a gene that is expressed in activated
      lymphocytes, hematopoietic stem cells and stem cells of a variety of tissues in
      mice. Despite decades of study its functions remain poorly defined. These studies
      explored the impact of expression of this stem cell associated gene in acute
      lymphoid leukemia. Higher levels of Ly6a/Sca-1 expression led to more aggressive
      leukemia growth in vivo and earlier death of hosts. Leukemias expressing higher
      levels of Ly6a/Sca-1 exhibited higher levels of matrix metalloproteinases. The
      results suggest the hypothesis that the more aggressive behavior of Ly6a/Sca-1
      expressing leukemias is due at least in part to greater capacity to degrade
      microenvironmental stroma and invade tissues. 

PMID- 24586464
TI  - Epidemiological evidence that garden birds are a source of human salmonellosis in
      England and Wales.
AB  - The importance of wild bird populations as a reservoir of zoonotic pathogens is
      well established. Salmonellosis is a frequently diagnosed infectious cause of
      mortality of garden birds in England and Wales, predominantly caused by
      Salmonella enterica subspecies enterica serovar Typhimurium definitive phage
      types 40, 56(v) and 160. In Britain, these phage types are considered highly host
      adapted with a high degree of genetic similarity amongst isolates, and in some
      instances are clonal. Pulsed field gel electrophoresis, however, demonstrated
      minimal variation amongst matched DT40 and DT56(v) isolates derived from
      passerine and human incidents of salmonellosis across England in 2000-2007. Also,
      during the period 1993-2012, similar temporal and spatial trends of infection
      with these S. Typhimurium phage types occurred in both the British garden bird
      and human populations; 1.6% of all S. Typhimurium (0.2% of all Salmonella)
      isolates from humans in England and Wales over the period 2000-2010. These
      findings support the hypothesis that garden birds act as the primary reservoir of
      infection for these zoonotic bacteria. Most passerine salmonellosis outbreaks
      identified occurred at and around feeding stations, which are likely sites of
      public exposure to sick or dead garden birds and their faeces. We, therefore,
      advise the public to practise routine personal hygiene measures when feeding wild
      birds and especially when handling sick wild birds. 

PMID- 24586465
TI  - Pharmacist interventions for prophylactic antibiotic use in urological inpatients
      undergoing clean or clean-contaminated operations in a Chinese hospital.
AB  - OBJECTIVES: To evaluate the impact and cost-benefit value of pharmacist
      interventions for prophylactic antibiotic use in surgical patients undergoing
      clean or clean-contaminated operations. METHODS: A pre-to-post intervention study
      was performed in the Department of Urological Surgery of a tertiary hospital.
      Patients admitted from January through June 2011, undergoing clean or clean
      contaminated surgery, served as the pre-intervention group; patients admitted
      from January through June 2012 formed the post-intervention group. Pharmacist
      interventions were performed for the surgeries in the post-intervention group.
      The criteria for the rational use of antibiotic prophylaxis were established by
      the hospital administration. The pharmacist interventions included real-time
      monitoring of medical records and controlling of the prescriptions of
      prophylactic antibiotics against the criteria. The pre- and post-intervention
      groups were then compared to evaluate the outcomes of the pharmacist
      interventions. A cost-benefit analysis was performed to determine the economic
      effects of implementing the pharmacist intervention on preoperative antibiotic
      prophylaxis. RESULTS: After the pharmacist intervention, a significant decrease
      was found in the rate of no indications for prophylactic antibiotic use (p =
      0.004), the rate of broad-spectrum antibiotic use (p<0.001), the rate of drug
      replacement (p<0.001) and the rate of prolonged duration of prophylaxis
      (p<0.001). Significant reductions were observed in the mean antibiotic cost
      (p<0.001), the mean duration of antibiotic prophylaxis (p<0.001) and the mean
      number of antibiotics used (p<0.001). A significant increase was observed in the
      rate of correct choice of antibiotics (p<0.001). The ratio of the net mean cost
      savings for antibiotics to the mean cost of pharmacist time was approximately
      18.79:1. CONCLUSION: Real-time interventions provided by a clinical pharmacist
      promoted rational use of prophylactic antibiotics, with a significant reduction
      in antibiotic costs, thus leading to favorable economic outcomes.

PMID- 24586466
TI  - Anti-osteoclastogenic activity of praeruptorin A via inhibition of p38/Akt-c-Fos
      NFATc1 signaling and PLCgamma-independent Ca2+ oscillation.
AB  - BACKGROUND: A decrease of bone mass is a major risk factor for fracture. Several
      natural products have traditionally been used as herbal medicines to prevent
      and/or treat bone disorders including osteoporosis. Praeruptorin A is isolated
      from the dry root extract of Peucedanum praeruptorum Dunn and has several
      biological activities, but its anti-osteoporotic activity has not been studied
      yet. MATERIALS AND METHODS: The effect of praeruptorin A on the differentiation
      of bone marrow-derived macrophages into osteoclasts was examined by phenotype
      assay and confirmed by real-time PCR and immunoblotting. The involvement of
      NFATc1 in the anti-osteoclastogenic action of praeruptorin A was evaluated by its
      lentiviral ectopic expression. Intracellular Ca(2+) levels were also measured.
      RESULTS: Praeruptorin A inhibited the RANKL-stimulated osteoclast differentiation
      accompanied by inhibition of p38 and Akt signaling, which could be the reason for
      praeruptorin A-downregulated expression levels of c-Fos and NFATc1, transcription
      factors that regulate osteoclast-specific genes, as well as osteoclast fusion
      related molecules. The anti-osteoclastogenic effect of praeruptorin A was rescued
      by overexpression of NFATc1. Praeruptorin A strongly prevented the RANKL-induced
      Ca(2+) oscillation without any changes in the phosphorylation of PLCgamma.
      CONCLUSION: Praeruptorin A could exhibit its anti-osteoclastogenic activity by
      inhibiting p38/Akt-c-Fos-NFATc1 signaling and PLCgamma-independent Ca(2+)
      oscillation.

PMID- 24586467
TI  - Unsaturated glycerophospholipids mediate heme crystallization: biological
      implications for hemozoin formation in the kissing bug Rhodnius prolixus.
AB  - Hemozoin (Hz) is a heme crystal produced by some blood-feeding organisms, as an
      efficient way to detoxify heme derived from hemoglobin digestion. In the
      triatomine insect Rhodnius prolixus, Hz is essentially produced by midgut
      extracellular phospholipid membranes known as perimicrovillar membranes (PMVM).
      Here, we investigated the role of commercial glycerophospholipids containing
      serine, choline and ethanolamine as headgroups and R. prolixus midgut lipids
      (RML) in heme crystallization. All commercial unsaturated forms of phospholipids,
      as well as RML, mediated fast and efficient beta-hematin formation by means of
      two kinetically distinct mechanisms: an early and fast component, followed by a
      late and slow one. The fastest reactions observed were induced by unsaturated
      forms of phosphatidylethanolamine (uPE) and phosphatidylcholine (uPC), with half
      lives of 0.04 and 0.7 minutes, respectively. beta-hematin crystal morphologies
      were strikingly distinct among groups, with uPE producing homogeneous regular
      brick-shaped crystals. Interestingly, uPC-mediated reactions resulted in two
      morphologically distinct crystal populations: one less representative group of
      regular crystals, resembling those induced by uPE, and the other largely
      represented by crystals with numerous sharp edges and tapered ends. Heme
      crystallization reactions induced by RML were efficient, with a heme to beta
      hematin conversion rate higher than 70%, but clearly slower (t1/2 of 9.9-17.7
      minutes) than those induced by uPC and uPE. Interestingly, crystals produced by
      RML were homogeneous in shape and quite similar to those mediated by uPE. Thus,
      beta-hematin formation can be rapidly and efficiently induced by unsaturated
      glycerophospholipids, particularly uPE and uPC, and may play a role on biological
      heme crystallization in R. prolixus midgut. 

PMID- 24586468
TI  - OpenStage: a low-cost motorized microscope stage with sub-micron positioning
      accuracy.
AB  - Recent progress in intracellular calcium sensors and other fluorophores has
      promoted the widespread adoption of functional optical imaging in the life
      sciences. Home-built multiphoton microscopes are easy to build, highly
      customizable, and cost effective. For many imaging applications a 3-axis
      motorized stage is critical, but commercially available motorization hardware
      (motorized translators, controller boxes, etc) are often very expensive.
      Furthermore, the firmware on commercial motor controllers cannot easily be
      altered and is not usually designed with a microscope stage in mind. Here we
      describe an open-source motorization solution that is simple to construct, yet
      far cheaper and more customizable than commercial offerings. The cost of the
      controller and motorization hardware are under $1000. Hardware costs are kept low
      by replacing linear actuators with high quality stepper motors. Electronics are
      assembled from commonly available hobby components, which are easy to work with.
      Here we describe assembly of the system and quantify the positioning accuracy of
      all three axes. We obtain positioning repeatability of the order of 1 MUm in X/Y
      and 0.1 MUm in Z. A hand-held control-pad allows the user to direct stage motion
      precisely over a wide range of speeds (10(-1) to 10(2) MUm.s(-1)), rapidly store
      and return to different locations, and execute "jumps" of a fixed size. In
      addition, the system can be controlled from a PC serial port. Our "OpenStage"
      controller is sufficiently flexible that it could be used to drive other devices,
      such as micro-manipulators, with minimal modifications.

PMID- 24586469
TI  - Population structure and evolution of Rhinoviruses.
AB  - Rhinoviruses, formerly known as Human rhinoviruses, are the most common cause of
      air-borne upper respiratory tract infections in humans. Rhinoviruses belong to
      the family Picornaviridae and are divided into three species namely, Rhinovirus
      A, -B and -C, which are antigenically diverse. Genetic recombination is found to
      be one of the important causes for diversification of Rhinovirus species.
      Although emerging lineages within Rhinoviruses have been reported, their
      population structure has not been studied yet. The availability of complete
      genome sequences facilitates study of population structure, genetic diversity and
      underlying evolutionary forces, such as mutation, recombination and selection
      pressure. Analysis of complete genomes of Rhinoviruses using a model-based
      population genetics approach provided a strong evidence for existence of seven
      genetically distinct subpopulations. As a result of diversification, Rhinovirus A
      and -C populations are divided into four and two subpopulations, respectively.
      Genetically, the Rhinovirus B population was found to be homogeneous. Intra
      species recombination was observed to be prominent in Rhinovirus A and -C
      species. Significant evidence of episodic positive selection was obtained for
      several sites within coding sequences of structural and non-structural proteins.
      This corroborates well with known phenotypic properties such as antigenicity of
      structural proteins. Episodic positive selection appears to be responsible for
      emergence of new lineages especially in Rhinovirus A. In summary, the Rhinovirus
      population is an ensemble of seven distinct lineages. In case of Rhinovirus A,
      intra-species recombination and episodic positive selection contribute to its
      further diversification. In case of Rhinovirus C, intra- and inter-species
      recombinations are responsible for observed diversity. Population genetics
      approach was further useful to analyze phylogenetic tree topologies pertaining to
      recombinant strains, especially when trees are derived using complete genomes.
      Understanding of population structure serves as a foundation for designing new
      vaccines and drugs as well as to explain emergence of drug resistance amongst
      subpopulations. 

PMID- 24586470
TI  - The impact of different DNA extraction kits and laboratories upon the assessment
      of human gut microbiota composition by 16S rRNA gene sequencing.
AB  - INTRODUCTION: Determining bacterial community structure in fecal samples through
      DNA sequencing is an important facet of intestinal health research. The impact of
      different commercially available DNA extraction kits upon bacterial community
      structures has received relatively little attention. The aim of this study was to
      analyze bacterial communities in volunteer and inflammatory bowel disease (IBD)
      patient fecal samples extracted using widely used DNA extraction kits in
      established gastrointestinal research laboratories. METHODS: Fecal samples from
      two healthy volunteers (H3 and H4) and two relapsing IBD patients (I1 and I2)
      were investigated. DNA extraction was undertaken using MoBio Powersoil and MP
      Biomedicals FastDNA SPIN Kit for Soil DNA extraction kits. PCR amplification for
      pyrosequencing of bacterial 16S rRNA genes was performed in both laboratories on
      all samples. Hierarchical clustering of sequencing data was done using the Yue
      and Clayton similarity coefficient. RESULTS: DNA extracted using the FastDNA kit
      and the MoBio kit gave median DNA concentrations of 475 (interquartile range 228
      561) and 22 (IQR 9-36) ng/uL respectively (p<0.0001). Hierarchical clustering of
      sequence data by Yue and Clayton coefficient revealed four clusters. Samples from
      individuals H3 and I2 clustered by patient; however, samples from patient I1
      extracted with the MoBio kit clustered with samples from patient H4 rather than
      the other I1 samples. Linear modelling on relative abundance of common bacterial
      families revealed significant differences between kits; samples extracted with
      MoBio Powersoil showed significantly increased Bacteroidaceae, Ruminococcaceae
      and Porphyromonadaceae, and lower Enterobacteriaceae, Lachnospiraceae,
      Clostridiaceae, and Erysipelotrichaceae (p<0.05). CONCLUSION: This study
      demonstrates significant differences in DNA yield and bacterial DNA composition
      when comparing DNA extracted from the same fecal sample with different extraction
      kits. This highlights the importance of ensuring that samples in a study are
      prepared with the same method, and the need for caution when cross-comparing
      studies that use different methods.

PMID- 24586471
TI  - Circulating immunoglobulins are not associated with intraplaque mast cell number
      and other vulnerable plaque characteristics in patients with carotid artery
      stenosis.
AB  - BACKGROUND: Recently, we have shown that intraplaque mast cell numbers are
      associated with atherosclerotic plaque vulnerability and with future
      cardiovascular events, which renders inhibition of mast cell activation of
      interest for future therapeutic interventions. However, the endogenous triggers
      that activate mast cells during the progression and destabilization of
      atherosclerotic lesions remain unidentified. Mast cells can be activated by
      immunoglobulins and in the present study, we aimed to establish whether specific
      immunoglobulins in plasma of patients scheduled for carotid endarterectomy were
      related to (activated) intraplaque mast cell numbers and plasma tryptase levels.
      In addition, the levels were related to other vulnerable plaque characteristics
      and baseline clinical data. METHODS AND RESULTS: OxLDL-IgG, total IgG and total
      IgE levels were measured in 135 patients who underwent carotid endarterectomy. No
      associations were observed between the tested plasma immunoglobulin levels and
      total mast cell numbers in atherosclerotic plaques. Furthermore, no associations
      were found between IgG levels and the following plaque characteristics: lipid
      core size, degree of calcification, number of macrophages or smooth muscle cells,
      amount of collagen and number of microvessels. Interestingly, statin use was
      negatively associated with plasma IgE and oxLDL-IgG levels. CONCLUSIONS: In
      patients suffering from carotid artery disease, total IgE, total IgG and oxLDL
      IgG levels do not associate with plaque mast cell numbers or other vulnerable
      plaque histopathological characteristics. This study thus does not provide
      evidence that the immunoglobulins tested in our cohort play a role in intraplaque
      mast cell activation or grade of atherosclerosis.

PMID- 24586472
TI  - Contrasting spatial patterns in active-fire and fire-suppressed Mediterranean
      climate old-growth mixed conifer forests.
AB  - In Mediterranean environments in western North America, historic fire regimes in
      frequent-fire conifer forests are highly variable both temporally and spatially.
      This complexity influenced forest structure and spatial patterns, but some of
      this diversity has been lost due to anthropogenic disruption of ecosystem
      processes, including fire. Information from reference forest sites can help
      management efforts to restore forests conditions that may be more resilient to
      future changes in disturbance regimes and climate. In this study, we characterize
      tree spatial patterns using four-ha stem maps from four old-growth, Jeffrey pine
      mixed conifer forests, two with active-fire regimes in northwestern Mexico and
      two that experienced fire exclusion in the southern Sierra Nevada. Most of the
      trees were in patches, averaging six to 11 trees per patch at 0.007 to 0.014 ha(
      1), and occupied 27-46% of the study areas. Average canopy gap sizes (0.04 ha)
      covering 11-20% of the area were not significantly different among sites. The
      putative main effects of fire exclusion were higher densities of single trees in
      smaller size classes, larger proportion of trees (>= 56%) in large patches (>= 10
      trees), and decreases in spatial complexity. While a homogenization of forest
      structure has been a typical result from fire exclusion, some similarities in
      patch, single tree, and gap attributes were maintained at these sites. These
      within-stand descriptions provide spatially relevant benchmarks from which to
      manage for structural heterogeneity in frequent-fire forest types.

PMID- 24586473
TI  - Prevalence of external injuries in small cetaceans in Aruban waters, southern
      Caribbean.
AB  - Aruba, located close to the coasts of Colombia and Venezuela, is one of the most
      densely populated islands in the Caribbean and supports a wide range of marine
      related socio-economic activities. However, little is known about the impacts of
      human activities on the marine environment. Injuries in marine mammals can be
      used to examine interactions with human activities and identify potential threats
      to the survival of populations. The prevalence of external injuries and tooth
      rake marks were examined in Atlantic spotted dolphin (Stenella frontalis) (n =
      179), bottlenose dolphin (Tursiops truncatus) (n = 76) and false killer whale
      (Pseudorca crassidens) (n = 71) in Aruban waters using photo identification
      techniques. Eleven injury categories were defined and linked to either human
      related activities or natural causes. All injury categories were observed. In
      total, 18.7% of all individuals had at least one injury. Almost half (41.7%) of
      the injuries could be attributed to human interactions, of which fishing gear was
      the most common cause (53.3%) followed by propeller hits (13.3%). Major
      disfigurements were observed in all three species and could be attributed to
      interactions with fishing gear. The results of this study indicate that fishing
      gear and propeller hits may pose threats to small and medium-sized cetaceans in
      Aruban waters. Thus, long-term monitoring of population trends is warranted.
      Shark-inflicted bite wounds were observed in Atlantic spotted dolphin and
      bottlenose dolphin. Bite wounds of cookie cutter sharks (Isistius sp.) were
      recorded in all three species, and include the first documented record of a
      cookie cutter shark bite in Atlantic spotted dolphin. This is one of the few
      studies which investigates the prevalence of injuries in cetaceans in the
      Caribbean. Further study is necessary to determine to which extent the injuries
      observed in Aruba affect the health and survival of local populations. 

PMID- 24586474
TI  - A unified comparison of stimulus-driven, endogenous mandatory and 'free choice'
      saccades.
AB  - It has been claimed that saccades arising from the three saccade triggering modes
      stimulus-driven, endogenous mandatory and 'free choice'-are driven by distinct
      mechanisms. We tested this claim by instructing observers to saccade from a white
      or black fixation disc to a same polarity (white or black) disc flashed for 100
      or 200 ms presented either alone (Exo), or together with an opposite (Endo) or
      same (EndoFC) polarity disc (blocked and mixed sessions). Target(s) and
      distractor were presented at three inter-stimulus intervals (ISIs) relative to
      the fixation offset (ISI: -200, 0, +200 ms) and were displayed at random
      locations within a 4 degrees -to-6 degrees  eccentricity range. The statistical
      analysis showed a global saccade triggering mode effect on saccade reaction times
      (SRTs) with Endo and EndoFC SRTs longer by about 27 ms than Exo-triggered ones
      but no effect for the Endo-EndoFC comparison. SRTs depended on both ISI (the "gap
      effect"), and target duration. Bimodal best fits of the SRT-distributions were
      found in 65% of cases with their count not different across the three triggering
      modes. Percentages of saccades in the 'fast' and 'slow' ranges of bimodal fits
      did not depend on the triggering modes either. Bimodality tests failed to assert
      a significant difference between these modes. An analysis of the timing of a
      putative inhibition by the distractor (Endo) or by the duplicated target (EndoFC)
      yielded no significant difference between Endo and EndoFC saccades but showed a
      significant shortening with ISI similar to the SRT shortening suggesting that the
      distractor-target mutual inhibition is itself inhibited by 'fixation' neurons.
      While other experimental paradigms may well sustain claims of distinct mechanisms
      subtending the three saccade triggering modes, as here defined reflexive and
      voluntary saccades appear to differ primarily in the effectiveness with which
      inhibitory processes slow down the initial fast rise of the saccade triggering
      signal.

PMID- 24586475
TI  - A genome-wide survey of genetic instability by transposition in Drosophila
      hybrids.
AB  - Hybridization between species is a genomic instability factor involved in
      increasing mutation rate and new chromosomal rearrangements. Evidence of a
      relationship between interspecific hybridization and transposable element
      mobilization has been reported in different organisms, but most studies are
      usually performed with particular TEs and do not discuss the real effect of
      hybridization on the whole genome. We have therefore studied whole genome
      instability of Drosophila interspecific hybrids, looking for the presence of new
      AFLP markers in hybrids. A high percentage (27-90%) of the instability markers
      detected corresponds to TEs belonging to classes I and II. Moreover, three
      transposable elements (Osvaldo, Helena and Galileo) representative of different
      families, showed an overall increase of transposition rate in hybrids compared to
      parental species. This research confirms the hypothesis that hybridization
      induces genomic instability by transposition bursts and suggests that genomic
      stress by transposition could contribute to a relaxation of mechanisms
      controlling TEs in the Drosophila genome. 

PMID- 24586476
TI  - Culex tarsalis vitellogenin gene promoters investigated in silico and in vivo
      using transgenic Drosophila melanogaster.
AB  - INTRODUCTION: Genetic modification, or transgenesis, is a powerful technique to
      investigate the molecular interactions between vector-borne pathogens and their
      arthropod hosts, as well as a potential novel approach for vector-borne disease
      control. Transgenesis requires the use of specific regulatory regions, or
      promoters, to drive expression of genes of interest in desired target tissues. In
      mosquitoes, the vast majority of described promoters are from Anopheles and Aedes
      mosquitoes. RESULTS: Culex tarsalis is one of the most important vectors of
      arboviruses (including West Nile virus) in North America, yet it has not been the
      subject of molecular genetic study. In order to facilitate molecular genetic work
      in this important vector species, we isolated four fat body-specific promoter
      sequences located upstream of the Cx. tarsalis vitellogenin genes (Vg1a, Vg1b,
      Vg2a and Vg2b). Sequences were analyzed in silico to identify requisite cis
      acting elements. The ability for promoter sequences to drive expression of green
      fluorescent protein (GFP) in vivo was investigated using transgenic Drosophila
      melanogaster. All four promoters were able to drive GFP expression but there was
      dramatic variation between promoters and between individual Drosophila lines,
      indicating significant position effects. The highest expression was observed in
      line Vg2bL3, which was >300-fold higher than the lowest line Vg1aL2. CONCLUSIONS:
      These new promoters will be useful for driving expression of genes of interest in
      transgenic Cx. tarsalis and perhaps other insects.

PMID- 24586477
TI  - The German Version of the Manchester Triage System and its quality criteria-
      first assessment of validity and reliability.
AB  - BACKGROUND: The German Version of the Manchester Triage System (MTS) has found
      widespread use in EDs across German-speaking Europe. Studies about the quality
      criteria validity and reliability of the MTS currently only exist for the English
      language version. Most importantly, the content of the German version differs
      from the English version with respect to presentation diagrams and change
      indicators, which have a significant impact on the category assigned. This
      investigation offers a preliminary assessment in terms of validity and inter
      rater reliability of the German MTS. METHODS: Construct validity of assigned MTS
      level was assessed based on comparisons to hospitalization (general / intensive
      care), mortality, ED and hospital length of stay, level of prehospital care and
      number of invasive diagnostics. A sample of 45,469 patients was used. Inter-rater
      agreement between an expert and triage nurses (reliability) was calculated
      separately for a subset group of 167 emergency patients. RESULTS: For general
      hospital admission the area under the curve (AUC) of the receiver operating
      characteristic was 0.749; for admission to ICU it was 0.871. An examination of
      MTS-level and number of deceased patients showed that the higher the priority
      derived from MTS, the higher the number of deaths (p<0.0001 / chi2 Test). There
      was a substantial difference in the 30-day survival among the 5 MTS categories
      (p<0.0001 / log-rank test).The AUC for the predict 30-day mortality was 0.613.
      Categories orange and red had the highest numbers of heart catheter and
      endoscopy. Category red and orange were mostly accompanied by an emergency
      physician, whereas categories blue and green were walk-in patients. Inter-rater
      agreement between expert triage nurses was almost perfect (kappa = 0.954).
      CONCLUSION: The German version of the MTS is a reliable and valid instrument for
      a first assessment of emergency patients in the emergency department.

PMID- 24586478
TI  - Non-adherence in patients on peritoneal dialysis: a systematic review.
AB  - BACKGROUND: It has been increasingly recognized that non-adherence is an
      important factor that determines the outcome of peritoneal dialysis (PD) therapy.
      There is therefore a need to establish the levels of non-adherence to different
      aspects of the PD regimen (dialysis procedures, medications, and dietary/fluid
      restrictions). METHODS: A systematic review of peer-reviewed literature was
      performed in PubMed, PsycINFO and CINAHL databases using PRISMA guidelines in May
      2013. Publications on non-adherence in PD were selected by two reviewers
      independently according to predefined inclusion and exclusion criteria. Relevant
      data on patient characteristics, measures, rates and factors associated with non
      adherence were extracted. The quality of studies was also evaluated independently
      by two reviewers according to a revised version of the Effective Public Health
      Practice Project assessment tool. RESULTS: The search retrieved 204 studies, of
      which a total of 25 studies met inclusion criteria. Reported rates of non
      adherence varied across studies: 2.6-53% for dialysis exchanges, 3.9-85% for
      medication, and 14.4-67% for diet/fluid restrictions. Methodological differences
      in measurement and definition of non-adherence underlie the observed variation.
      Factors associated with non-adherence that showed a degree of consistency were
      mostly socio-demographical, such as age, employment status, ethnicity, sex, and
      time period on PD treatment. CONCLUSION: Non-adherence to different dimensions of
      the dialysis regimen appears to be prevalent in PD patients. There is a need for
      further, high-quality research to explore these factors in more detail, with the
      aim of informing intervention designs to facilitate adherence in this patient
      population.

PMID- 24586480
TI  - Adjective metaphors evoke negative meanings.
AB  - Previous metaphor studies have paid much attention to nominal metaphors and
      predicative metaphors, but little attention has been given to adjective
      metaphors. Although some studies have focused on adjective metaphors, they only
      examined differences in the acceptability of various types of adjective
      metaphors. This paper explores the cognitive effects evoked by adjective
      metaphors. Three psychological experiments revealed that (1) adjective metaphors,
      especially those modified by color adjectives, tend to evoke negative effect; (2)
      although the meanings of metaphors are basically affected by the meanings of
      their vehicles, when a vehicle has a neutral meaning, negative meanings are
      evoked most frequently for adjective metaphors compared to nominal and
      predicative metaphors; (3) negative meanings evoked by adjective metaphors are
      related to poeticness, and poetic metaphors evoke negative meanings more easily
      than less poetic metaphors. Our research sheds new light on studies of the use of
      metaphor, which is one of the most basic human cognitive abilities. 

PMID- 24586479
TI  - Stromal cells from human decidua exert a strong inhibitory effect on NK cell
      function and dendritic cell differentiation.
AB  - Stromal cells (SC) are an important component of decidual tissues where they are
      in strict proximity with both NK and CD14(+) myelomonocytic cells that play a
      role in the maintenance of pregnancy. In this study we analyzed whether decidual
      SC (DSC) could exert a regulatory role on NK and CD14(+) cells that migrate from
      peripheral blood (PB) to decidua during pregnancy. We show that DSCs inhibit the
      IL15-mediated up-regulation of major activating NK receptors in PB-derived NK
      cells. In addition, the IL15-induced NK cell proliferation, cytolytic activity
      and IFN-gamma production were severely impaired. DSCs sharply inhibited dendritic
      cells differentiation and their ability to induce allogeneic T cell
      proliferation. Indoleamine 2,3-dioxygenase (IDO) and prostaglandin E2 (PGE2)
      mediated the inhibitory effect of DSCs. Our results strongly suggest an important
      role of DSCs in preventing potentially dangerous immune response, thus
      contributing to maintenance of pregnancy. 

PMID- 24586481
TI  - Inflammation enhances IL-2 driven differentiation of cytolytic CD4 T cells.
AB  - Cytolytic CD4 T cells (CD4 CTL) have been identified in vivo in response to viral
      infections; however, the factors necessary for driving the cytolytic phenotype
      have not been fully elucidated. Our previously published work suggests IL-2 may
      be the master regulator of perforin-mediated cytotoxicity in CD4 effectors. To
      further dissect the role of IL-2 in CD4 CTL generation, T cell receptor
      transgenic mice deficient in the ability to produce IL-2 or the high affinity IL
      2 receptor (IL-2Ralpha, CD25) were used. Increasing concentrations of IL-2 were
      necessary to drive perforin (Prf) expression and maximal cytotoxicity. Granzyme B
      (GrB) expression and killing correlated with STAT5 activation and CD25 expression
      in vitro, suggesting that signaling through the high affinity IL-2R is critical
      for full cytotoxicity. IL-2 signaling was also necessary in vivo for inducing the
      Th1 phenotype and IFN-gamma expression in CD4 T cells during influenza A (IAV)
      infection. In addition, GrB expression, as measured by mean fluorescent
      intensity, was decreased in CD25 deficient cells; however, the frequency of CD4
      cells expressing GrB was unchanged. Similarly, analysis of cytolytic markers such
      as CD107a/b and Eomesodermin indicate high IL-2Ralpha expression is not necessary
      to drive the CD4 CTL phenotype during IAV infection. Thus, inflammatory signals
      induced by viral infection may overcome the need for strong IL-2 signals in
      driving cytotoxicity in CD4 cells.

PMID- 24586482
TI  - rtM204Q may serve as a novel lamivudine-resistance-associated mutation of
      hepatitis B virus.
AB  - BACKGROUND AND AIMS: Lamivudine (LAM) is still widely used for anti-HBV therapy
      in China. The study aimed to clarify whether a newly-found rtM204Q mutation from
      patients was associated with the drug resistance. METHODS: HBV complete reverse
      transcriptase region was screened by direct sequencing and verified by clonal
      sequencing. Replication-competent plasmids containing patient-derived 1.1mer
      mutant or wild-type viral genome were constructed and transfected into HepG2
      cells. After cultured with or without serially-diluted antiviral drugs,
      intracellular HBV replicative intermediates were quantitated for calculating the
      50% effective concentration of drug (EC50). RESULTS: A total of 12,000 serum
      samples of 9,830 patients with chronic HBV infection were screened. rtM204Q
      mutation was detected in seven LAM-refractory patients. By contrast,
      rtM204I/rtM204V mutations were detected in 2,502 patients' samples. The rtM204Q
      emerged either alone or in concomitance with rtM204I/rtM204V, and all were
      accompanied with virologic breakthrough in clinical course. Clonal sequencing
      verified that rtM204Q mutant was predominant in viral quasispecies of these
      samples. Phenotypic analysis showed that rtM204Q mutant had 89.9% of replication
      capacity and 76-fold increased LAM EC50 of the concomitant wild-type strain. By
      contrast, rtM204I mutant in the sample had lower replication capacity and higher
      LAM resistance (46.3% and 1396-fold increased LAM EC50 of the wild-type strain)
      compared to rtM204Q mutant. rtM204Q mutant was susceptible to adefovir dipivoxil
      (ADV) in vitro and ADV/ADV+LAM rescue therapy in clinic. CONCLUSION: rtM204Q is
      suggested to be a novel LAM-resistance-associated mutation. It conferred a
      moderate resistance with higher competent natural replication capacity compared
      to rtM204I mutation.

PMID- 24586483
TI  - A functional polymorphism in the promoter region of microRNA-146a is associated
      with the risk of Alzheimer disease and the rate of cognitive decline in patients.
AB  - miR146a is well known for its regulatory role in the immune response and
      inflammation. Recent studies have demonstrated the links between miR146a and
      Alzheimer disease (AD) and suggested that miR146a may be involved in
      neuroinflammation and the metabolism of amyloid-beta (Abeta), which are critical
      events in AD pathology. Although genetic studies have focused on the association
      between the miR146a gene and susceptibility to several diseases, no association
      study of miR146a variability with AD has been conducted. In this report, we
      performed a case-control association study to analyze the genotype and allele
      distributions of the miR146a, rs2910464 and rs57095329 polymorphisms in a Chinese
      population consisting of 292 AD cases and 300 healthy controls. We found a
      significant difference in the genotypes and allele frequencies of rs57095329
      between the AD cases and the controls (p = 0.0147 and p = 0.0184, respectively),
      where the AA genotype of rs57095329 was associated with an increased risk of AD
      as well the cognitive decline in AD patients. Additionally, the AA genotype of
      rs57095329 exhibited significantly higher miR146a expression than the GG+GA
      genotypes of rs2910164 in the peripheral blood cells (PBMCs) of healthy
      individuals and had a stronger effect on the production of IL-6 and IL-1beta when
      the cells were stimulated with LPS. Our data provide preliminary evidence that
      the rs57095329 polymorphism in the miR146a promoter is involved in the genetic
      susceptibility to AD, and this risk AA genotype may increase the expression of
      miR146a and influence certain proinflammatory cytokines, thus playing a role in
      the pathogenesis of AD.

PMID- 24586484
TI  - Neuronal-specific deficiency of the splicing factor Tra2b causes apoptosis in
      neurogenic areas of the developing mouse brain.
AB  - Alternative splicing (AS) increases the informational content of the genome and
      is more prevalent in the brain than in any other tissue. The splicing factor
      Tra2b (Sfrs10) can modulate splicing inclusion of exons by specifically detecting
      GAA-rich binding motifs and its absence causes early embryonic lethality in mice.
      TRA2B has been shown to be involved in splicing processes of Nasp (nuclear
      autoantigenic sperm protein), MAPT (microtubule associated protein tau) and SMN
      (survival motor neuron), and is therefore implicated in spermatogenesis and
      neurological diseases like Alzheimer's disease, dementia, Parkinson's disease and
      spinal muscular atrophy. Here we generated a neuronal-specific Tra2b knock-out
      mouse that lacks Tra2b expression in neuronal and glial precursor cells by using
      the Nestin-Cre. Neuronal-specific Tra2b knock-out mice die immediately after
      birth and show severe abnormalities in cortical development, which are caused by
      massive apoptotic events in the ventricular layers of the cortex, demonstrating a
      pivotal role of Tra2b for the developing central nervous system. Using whole
      brain RNA on exon arrays we identified differentially expressed alternative exons
      of Tubulindelta1 and Shugoshin-like2 as in vivo targets of Tra2b. Most
      interestingly, we found increased expression of the cyclin dependent kinase
      inhibitor 1a (p21) which we could functionally link to neuronal precursor cells
      in the affected brain regions. We provide further evidence that the absence of
      Tra2b causes p21 upregulation and ultimately cell death in NSC34 neuronal-like
      cells. These findings demonstrate that Tra2b regulates splicing events essential
      for maintaining neuronal viability during development. Apoptotic events triggered
      via p21 might not be restricted to the developing brain but could possibly be
      generalized to the whole organism and explain early embryonic lethality in Tra2b
      depleted mice. 

PMID- 24586485
TI  - Genomic characterization of novel Listeria monocytogenes serotype 4b variant
      strains.
AB  - Over 90% of the human listeriosis cases are caused by Listeria monocytogenes
      serotypes 1/2a, 1/2b and 4b strains. As an alternative to antigen-antibody based
      serotyping, a PCR-based method for serogrouping has been developed and validated.
      In this communication, we report an in-depth analysis of five 4b variant strains,
      four clinical isolates from Australia and one environmental isolate from USA.
      Although these five strains were serotype 4b by classical serotyping method, the
      serogrouping PCR profiles of these strains show the presence of a 1/2a-3a
      specific amplicon in addition to the standard 4b-4d-4e specific amplicons. These
      strains were further analyzed by pulsed field gel electrophoresis, binary gene
      typing, multi-locus variable-number-tandem-repeat analysis and a high density pan
      genomic Listeria microarray. Using these sub-typing results, the clinical
      isolates were grouped into two distinct genomic groups- one of which could be
      part of an unidentified outbreak. The microarray results when compared with our
      database of other 4b outbreak isolates indicated that the serotype 4b variant
      strains represent very different genotypic profiles than the known reported 4b
      outbreak strains representing major epidemic clones. The acquisition of serotype
      1/2a gene clusters by the 4b variant strains appears to be independent in origin,
      spanning large areas of geographical and temporal space and may indicate
      predisposition of some 4b strains towards accepting DNA from related organisms. 

PMID- 24586486
TI  - Amelioration of aspirin induced oxidative impairment and apoptotic cell death by
      a novel antioxidant protein molecule isolated from the herb Phyllanthus niruri.
AB  - Aspirin has been used for a long time as an analgesic and anti-pyretic drug.
      Limitations of its use, however, remain for the gastro-intestinal side effects
      and erosions. Although the role of aspirin on gastro-intestinal injury has been
      extensively studied, the molecular mechanisms underlying aspirin-induced liver
      and spleen pathophysiology are poorly defined. The present study has been
      conducted to investigate whether phyllanthus niruri protein (PNP) possesses any
      protective role against aspirin mediated liver and spleen tissue toxicity, and if
      so, what signaling pathways it utilizes to convey its protective action. Aspirin
      administration in mice enhanced serum marker (ALP) levels, reactive oxygen
      species (ROS) generation, reduced antioxidant power and altered oxidative stress
      related biochemical parameters in liver and spleen tissues. Moreover, we observed
      that aspirin intoxication activated both the extrinsic and intrinsic apoptotic
      pathways, as well as down regulated NF-kappaB activation and the phosphorylation
      of p38 and JNK MAPKs. Histological assessments and TUNEL assay also supported
      that aspirin induced tissue damages are apoptotic in nature. PNP treatment after
      aspirin exposure effectively neutralizes all these abnormalities via the
      activation of survival PI3k/Akt pathways. Combining all results suggest that PNP
      could be a potential protective agent to protect liver and spleen from the
      detrimental effects of aspirin. 

PMID- 24586487
TI  - Distinct structural features of the peroxide response regulator from group A
      Streptococcus drive DNA binding.
AB  - Group A streptococcus (GAS, Streptococcus pyogenes) is a strict human pathogen
      that causes severe, invasive diseases. GAS does not produce catalase, but has an
      ability to resist killing by reactive oxygen species (ROS) through novel
      mechanisms. The peroxide response regulator (PerR), a member of ferric uptake
      regulator (Fur) family, plays a key role for GAS to cope with oxidative stress by
      regulating the expression of multiple genes. Our previous studies have found that
      expression of an iron-binding protein, Dpr, is under the direct control of PerR.
      To elucidate the molecular interactions of PerR with its cognate promoter, we
      have carried out structural studies on PerR and PerR-DNA complex. By combining
      crystallography and small-angle X-ray scattering (SAXS), we confirmed that the
      determined PerR crystal structure reflects its conformation in solution. Through
      mutagenesis and biochemical analysis, we have identified DNA-binding residues
      suggesting that PerR binds to the dpr promoter at the per box through a winged
      helix motif. Furthermore, we have performed SAXS analysis and resolved the
      molecular architecture of PerR-DNA complex, in which two 30 bp DNA fragments wrap
      around two PerR homodimers by interacting with the adjacent positively-charged
      winged-helix motifs. Overall, we provide structural insights into molecular
      recognition of DNA by PerR and define the hollow structural arrangement of PerR
      30bpDNA complex, which displays a unique topology distinct from currently
      proposed DNA-binding models for Fur family regulators. 

PMID- 24586488
TI  - GmFT4, a homolog of FLOWERING LOCUS T, is positively regulated by E1 and
      functions as a flowering repressor in soybean.
AB  - The major maturity gene E1 has the most prominent effect on flowering time and
      photoperiod sensitivity of soybean, but the pathway mediated by E1 is largely
      unknown. Here, we found the expression of GmFT4, a homolog of Flowering Locus T,
      was strongly up-regulated in transgenic soybean overexpressing E1, whereas
      expression of flowering activators, GmFT2a and GmFT5a, was suppressed. GmFT4
      expression was strongly up-regulated by long days exhibiting a diurnal rhythm,
      but down-regulated by short days. Notably, the basal expression level of GmFT4
      was elevated when transferred to continous light, whereas repressed when
      transferred to continuous dark. GmFT4 was primarily expressed in fully expanded
      leaves. Transcript abundance of GmFT4 was significantly correlated with that of
      functional E1, as well as flowering time phenotype in different cultivars.
      Overexpression of GmFT4 delayed the flowering time in transgenic Arabidopsis.
      Taken together, we propose that GmFT4 acts downstream of E1 and functions as a
      flowering repressor, and the balance of two antagonistic factors (GmFT4 vs
      GmFT2a/5a) determines the flowering time of soybean. 

PMID- 24586489
TI  - Drug facilitated sexual assault: detection and stability of benzodiazepines in
      spiked drinks using gas chromatography-mass spectrometry.
AB  - Benzodiazepines are detected in a significant number of drug facilitated sexual
      assaults (DFSA). Whilst blood and urine from the victim are routinely analysed,
      due to the delay in reporting DFSA cases and the short half lives of most of
      these drugs in blood and urine, drug detection in such samples is problematic.
      Consideration of the drinks involved and analysis for drugs may start to address
      this. Here we have reconstructed the 'spiking' of three benzodiazepines
      (diazepam, flunitrazepam and temazepam) into five drinks, an alcopop (flavoured
      alcoholic drink), a beer, a white wine, a spirit, and a fruit based non-alcoholic
      drink (J2O) chosen as representative of those drinks commonly used by women in 16
      24 year old age group. Using a validated GC-MS method for the simultaneous
      detection of these drugs in the drinks we have studied the storage stability of
      the benzodiazepines under two different storage conditions, uncontrolled room
      temperature and refrigerator (4 degrees C) over a 25 day period. All drugs could
      be detected in all beverages over this time period. Diazepam was found to be
      stable in all of the beverages, except the J2O, under both storage conditions.
      Flunitrazepam and temazepam were found not to be stable but were detectable (97%
      loss of temazepam and 39% loss of flunitrazepam from J2O). The recommendations
      from this study are that there should be a policy change and that drinks thought
      to be involved in DFSA cases should be collected and analysed wherever possible
      to support other evidence types. 

PMID- 24586490
TI  - Effect of darapladib treatment on endarterectomy carotid plaque lipoprotein
      associated phospholipase A2 activity: a randomized, controlled trial.
AB  - BACKGROUND: The aim of this study was to assess the effects of darapladib, a
      selective oral investigational lipoprotein-associated phospholipase A2 inhibitor,
      on both plasma and plaque lipoprotein-associated phospholipase A2 activity.
      METHODS: Patients undergoing elective carotid endarterectomy were randomized to
      darapladib 40 mg (n = 34), 80 mg (n = 34), or placebo (n = 34) for 14 days,
      followed by carotid endarterectomy 24 hours after the last dose of study
      medication. RESULTS: Darapladib 40 mg and 80 mg reduced plasma lipoprotein
      associated phospholipase A2 activity by 52% and 81%, respectively, versus placebo
      (both P<0.001). Significant reductions in plaque lipoprotein-associated
      phospholipase A2 activity were also observed compared with placebo (P<0.0001),
      which equated to a 52% and 80% decrease compared with placebo. No significant
      differences were observed between groups in plaque lysophosphatidylcholine
      content or other biomarkers, although a dose-dependent decrease in plaque matrix
      metalloproteinase-9 mRNA expression was observed with darapladib 80 mg (P = 0.053
      vs placebo). In a post-hoc analysis, plaque caspase-3 (P<0.001) and caspase-8
      (P<0.05) activity were found to be significantly lower in the darapladib 80-mg
      group versus placebo. No major safety concerns were identified in the study.
      CONCLUSIONS: Short-term treatment (14 +/- 4 days) with darapladib produced a
      robust, dose-dependent reduction in plasma lipoprotein-associated phospholipase
      A2 activity. More importantly, darapladib demonstrated placebo-corrected
      reductions in carotid plaque lipoprotein-associated phospholipase A2 activity of
      similar magnitude. Darapladib was generally well tolerated and no safety concerns
      were identified. Additional studies of longer duration are needed to explore
      whether these pharmacodynamic effects are associated with improved clinical
      outcomes, as might be hypothesized.

PMID- 24586491
TI  - Gender-based screening for chlamydial infection and divergent infection trends in
      men and women.
AB  - OBJECTIVES: To assess the potential impact of chlamydial screening policy that
      recommends routine screening of women but not men. METHODS: Population surveys of
      probability samples of Baltimore adults aged 18 to 35 years in 1997-1998 and 2006
      2009 collected biospecimens to estimate trends in undiagnosed chlamydial
      infection. Survey estimates are compared to surveillance data on diagnosed
      chlamydial infections reported to the Health Department. RESULTS: Prevalence of
      undiagnosed chlamydial infection among men increased from 1.6% to 4.0%, but it
      declined from 4.3% to 3.1% among women (p = 0.028 for test of interaction). The
      annual (average) number of diagnosed infections was substantially higher among
      women than men in both time periods and increased among both men and women.
      Undiagnosed infection prevalence was substantially higher among black than non
      black adults (4.0% vs 1.2%, p = 0.042 in 1997-98 and 5.5% vs 0.7%, p<0.001 in
      2006-09). CONCLUSION: Divergent trends in undiagnosed chlamydial infection by
      gender parallel divergent screening recommendations that encourage chlamydial
      testing for women but not for men.

PMID- 24586492
TI  - Elaboration versus suppression of cued memories: influence of memory recall
      instruction and success on parietal lobe, default network, and hippocampal
      activity.
AB  - Functional imaging studies of episodic memory retrieval consistently report task
      evoked and memory-related activity in the medial temporal lobe, default network
      and parietal lobe subregions. Associated components of memory retrieval, such as
      attention-shifts, search, retrieval success, and post-retrieval processing also
      influence regional activity, but these influences remain ill-defined. To better
      understand how top-down control affects the neural bases of memory retrieval, we
      examined how regional activity responses were modulated by task goals during
      recall success or failure. Specifically, activity was examined during memory
      suppression, recall, and elaborative recall of paired-associates. Parietal lobe
      was subdivided into dorsal (BA 7), posterior ventral (BA 39), and anterior
      ventral (BA 40) regions, which were investigated separately to examine
      hypothesized distinctions in sub-regional functional responses related to
      differential attention-to-memory and memory strength. Top-down suppression of
      recall abolished memory strength effects in BA 39, which showed a task-negative
      response, and BA 40, which showed a task-positive response. The task-negative
      response in default network showed greater negatively-deflected signal for
      forgotten pairs when task goals required recall. Hippocampal activity was task
      positive and was influenced by memory strength only when task goals required
      recall. As in previous studies, we show a memory strength effect in parietal lobe
      and hippocampus, but we show that this effect is top-down controlled and
      sensitive to whether the subject is trying to suppress or retrieve a memory.
      These regions are all implicated in memory recall, but their individual activity
      patterns show distinct memory-strength-related responses when task goals are
      varied. In parietal lobe, default network, and hippocampus, top-down control can
      override the commonly identified effects of memory strength. 

PMID- 24586493
TI  - A scallop IGF binding protein gene: molecular characterization and association of
      variants with growth traits.
AB  - BACKGROUND: Scallops represent economically important aquaculture shellfish. The
      identification of genes and genetic variants related to scallop growth could
      benefit high-yielding scallop breeding. The insulin-like growth factor (IGF)
      system is essential for growth and development, with IGF binding proteins
      (IGFBPs) serving as the major regulators of IGF actions. Although an effect of
      IGF on growth was detected in bivalve, IGFBP has not been reported, and members
      of the IGF system have not been characterized in scallop. RESULTS: We cloned and
      characterized an IGFBP (PyIGFBP) gene from the aquaculture bivalve species, Yesso
      scallop (Patinopecten yessoensis, Jay, 1857). Its full-length cDNA sequence was
      1,445 bp, with an open reading frame of 378 bp, encoding 125 amino acids, and its
      genomic sequence was 10,193 bp, consisting of three exons and two introns. The
      amino acid sequence exhibited the characteristics of IGFBPs, including multiple
      cysteine residues and relatively conserved motifs in the N-terminal and C
      terminal domains. Expression analysis indicated that PyIGFBP was expressed in all
      the tissues and developmental stages examined, with a significantly higher level
      in the mantle than in other tissues and a significantly higher level in gastrulae
      and trochophore larvae than in other stages. Furthermore, three single nucleotide
      polymorphisms (SNPs) were identified in this gene. SNP c.1054A>G was
      significantly associated with both shell and soft body traits in two populations,
      with the highest trait values in GG type scallops and lowest in AG type ones.
      CONCLUSION: We cloned and characterized an IGFBP gene in a bivalve, and this
      report also represents the first characterizing an IGF system gene in scallops. A
      SNP associated with scallop growth for both the shell and soft body was
      identified in this gene. In addition to providing a candidate marker for scallop
      breeding, our results also suggest the role of PyIGFBP in scallop growth.

PMID- 24586494
TI  - A prospective cohort study of cutaneous leishmaniasis risk and opium addiction in
      south eastern Iran.
AB  - Opium addiction and cutaneous leishmaniasis (CL) are endemic in different parts
      of Iran, particularly in Bam, where a massive earthquake occurred. This study was
      designed to compare the incidence rate and severity of CL cases among opium
      addicted and non-addicted individuals in south-eastern Iran. This study was
      carried out as a prospective cohort by active house-to-house visits of 1,481
      habitants in Bam. CL cases were confirmed by smear and identification of
      Leishmania species was performed using nested-PCR. The data was analyzed by
      chi(2) and t-tests, using SPSS software and also Kaplan-Meier survival curve and
      long-rank test in Stata 11.2 and P<0.05 was considered as significant. A total of
      904 individuals consisting of 226 opium addicted and 678 non-addicted individuals
      were followed-up for a period of seven years. The two cohorts were similar in
      terms of age, sex and place of residency. A similar pattern of incidence was
      observed among the two cohort groups. In contrast, the severity of CL in terms of
      the number, duration and the size of the lesions in opium addicted individuals
      was significantly (P<0.001) higher than non-opium addicted individuals. In
      conclusion, the present findings indicate that there is no relationship between
      the incidence of CL and opium addiction. 

PMID- 24586495
TI  - Cystic fibrosis bronchial epithelial cells are lipointoxicated by membrane
      palmitate accumulation.
AB  - The F508del-CFTR mutation, responsible for Cystic Fibrosis (CF), leads to the
      retention of the protein in the endoplasmic reticulum (ER). The mistrafficking of
      this mutant form can be corrected by pharmacological chaperones, but these
      molecules showed limitations in clinical trials. We therefore hypothesized that
      important factors in CF patients may have not been considered in the in vitro
      assays. CF has also been associated with an altered lipid homeostasis, i. e. a
      decrease in polyunsaturated fatty acid levels in plasma and tissues. However, the
      precise fatty acyl content of membrane phospholipids from human CF bronchial
      epithelial cells had not been studied to date. Since the saturation level of
      phospholipids can modulate crucial membrane properties, with potential impacts on
      membrane protein folding/trafficking, we analyzed this parameter for freshly
      isolated bronchial epithelial cells from CF patients. Interestingly, we could
      show that Palmitate, a saturated fatty acid, accumulates within
      Phosphatidylcholine (PC) in CF freshly isolated cells, in a process that could
      result from hypoxia. The observed PC pattern can be recapitulated in the CFBE41o(
      ) cell line by incubation with 100 uM Palmitate. At this concentration, Palmitate
      induces an ER stress, impacts calcium homeostasis and leads to a decrease in the
      activity of the corrected F508del-CFTR. Overall, these data suggest that
      bronchial epithelial cells are lipointoxicated by hypoxia-related Palmitate
      accumulation in CF patients. We propose that this phenomenon could be an
      important bottleneck for F508del-CFTR trafficking correction by pharmacological
      agents in clinical trials. 

PMID- 24586496
TI  - Interleukin-6 in serum and in synovial fluid enhances the differentiation between
      periprosthetic joint infection and aseptic loosening.
AB  - The preoperative differentiation between septic and aseptic loosening after total
      hip or knee arthroplasty is essential for successful therapy and relies in part
      on biomarkers. The objective of this study was to assess synovial and serum
      levels of inflammatory proteins as diagnostic tool for periprosthetic joint
      infection and compare their accuracy with standard tests. 120 patients presenting
      with a painful knee or hip endoprosthesis for surgical revision were included in
      this prospective trial. Blood samples and samples of intraoperatively acquired
      joint fluid aspirate were collected. White blood cell count, C-reactive protein,
      procalcitonin and interleukin-6 were determined. The joint aspirate was analyzed
      for total leukocyte count and IL-6. The definite diagnosis of PJI was determined
      on the basis of purulent synovial fluid, histopathology and microbiology. IL-6 in
      serum showed significantly higher values in the PJI group as compared to aseptic
      loosening and control, with specificity at 58.3% and a sensitivity of 79.5% at a
      cut-off value of 2.6 pg/ml. With a cut-off >6.6 pg/ml, the specificity increased
      to 88.3%. IL-6 in joint aspirate had, at a cut-off of >2100 pg/ml, a specificity
      of 85.7% and sensitivity of 59.4%. At levels >9000 pg/ml, specificity was almost
      at 100% with sensitivity just below 50%, so PJI could be considered proven with
      IL-6 levels above this threshold. Our data supports the published results on IL-6
      as a biomarker in PJI. In our large prospective cohort of revision arthroplasty
      patients, the use of IL-6 in synovial fluid appears to be a more accurate marker
      than either the white blood cell count or the C-reactive protein level in serum
      for the detection of periprosthetic joint infection. On the basis of the results
      we recommend the use of the synovial fluid biomarker IL-6 for the diagnosis of
      periprosthetic joint infection following total hip and knee arthroplasty. 

PMID- 24586497
TI  - Quality of malaria case management in Malawi: results from a nationally
      representative health facility survey.
AB  - BACKGROUND: Malaria is endemic throughout Malawi, but little is known about
      quality of malaria case management at publicly-funded health facilities, which
      are the major source of care for febrile patients. METHODS: In April-May 2011, we
      conducted a nationwide, geographically-stratified health facility survey to
      assess the quality of outpatient malaria diagnosis and treatment. We enrolled
      patients presenting for care and conducted exit interviews and re-examinations,
      including reference blood smears. Moreover, we assessed health worker readiness
      (e.g., training, supervision) and health facility capacity (e.g. availability of
      diagnostics and antimalarials) to provide malaria case management. All analyses
      accounted for clustering and unequal selection probabilities. We also used survey
      weights to produce estimates of national caseloads. RESULTS: At the 107
      facilities surveyed, most of the 136 health workers interviewed (83%) had
      received training on malaria case management. However, only 24% of facilities had
      functional microscopy, 15% lacked a thermometer, and 19% did not have the first
      line artemisinin-based combination therapy (ACT), artemether-lumefantrine, in
      stock. Of 2,019 participating patients, 34% had clinical malaria (measured fever
      or self-reported history of fever plus a positive reference blood smear). Only
      67% (95% confidence interval (CI): 59%, 76%) of patients with malaria were
      correctly prescribed an ACT, primarily due to missed malaria diagnosis. Among
      patients without clinical malaria, 31% (95% CI: 24%, 39%) were prescribed an ACT.
      By our estimates, 1.5 million of the 4.4 million malaria patients seen in public
      facilities annually did not receive correct treatment, and 2.7 million patients
      without clinical malaria were inappropriately given an ACT. CONCLUSIONS: Malawi
      has a high burden of uncomplicated malaria but nearly one-third of all patients
      receive incorrect malaria treatment, including under- and over-treatment. To
      improve malaria case management, facilities must at minimum have basic case
      management tools, and health worker performance in diagnosing malaria must be
      improved.

PMID- 24586498
TI  - Major membrane protein TDE2508 regulates adhesive potency in Treponema denticola.
AB  - The cultivation and genetic manipulation of Treponema denticola, a Gram-negative
      oral spirochaeta associated with periodontal diseases, is still challenging. In
      this study, we formulated a simple medium based on a commercially available one,
      and established a transformation method with high efficiency. We then analyzed
      proteins in a membrane fraction in T. denticola and identified 16 major membrane
      associated proteins, and characterized one of them, TDE2508, whose biological
      function was not yet known. Although this protein, which exhibited a complex
      conformation, was presumably localized in the outer membrane, we did not find
      conclusive evidence that it was exposed on the cell surface. Intriguingly, a
      TDE2508-deficient mutant exhibited significantly increased biofilm formation and
      adherent activity on human gingival epithelial cells. However, the protein
      deficiency did not alter autoaggregation, coaggregation with Porphyromonas
      gingivalis, hemagglutination, cell surface hydrophobicity, motility, or
      expression of Msp which was reported to be an adherent molecule in this bacteria.
      In conclusion, the major membrane protein TDE2508 regulates biofilm formation and
      the adhesive potency of T. denticola, although the underlying mechanism remains
      unclear. 

PMID- 24586499
TI  - Contraction of online response to major events.
AB  - Quantifying regularities in behavioral dynamics is of crucial interest for
      understanding collective social events such as panics or political revolutions.
      With the widespread use of digital communication media it has become possible to
      study massive data streams of user-created content in which individuals express
      their sentiments, often towards a specific topic. Here we investigate messages
      from various online media created in response to major, collectively followed
      events such as sport tournaments, presidential elections, or a large snow storm.
      We relate content length and message rate, and find a systematic correlation
      during events which can be described by a power law relation--the higher the
      excitation, the shorter the messages. We show that on the one hand this effect
      can be observed in the behavior of most regular users, and on the other hand is
      accentuated by the engagement of additional user demographics who only post
      during phases of high collective activity. Further, we identify the distributions
      of content lengths as lognormals in line with statistical linguistics, and
      suggest a phenomenological law for the systematic dependence of the message rate
      to the lognormal mean parameter. Our measurements have practical implications for
      the design of micro-blogging and messaging services. In the case of the existing
      service Twitter, we show that the imposed limit of 140 characters per message
      currently leads to a substantial fraction of possibly dissatisfying to compose
      tweets that need to be truncated by their users.

PMID- 24586500
TI  - Reverse zoonotic disease transmission (zooanthroponosis): a systematic review of
      seldom-documented human biological threats to animals.
AB  - BACKGROUND: Research regarding zoonotic diseases often focuses on infectious
      diseases animals have given to humans. However, an increasing number of reports
      indicate that humans are transmitting pathogens to animals. Recent examples
      include methicillin-resistant Staphylococcus aureus, influenza A virus,
      Cryptosporidium parvum, and Ascaris lumbricoides. The aim of this review was to
      provide an overview of published literature regarding reverse zoonoses and
      highlight the need for future work in this area. METHODS: An initial broad
      literature review yielded 4763 titles, of which 4704 were excluded as not meeting
      inclusion criteria. After careful screening, 56 articles (from 56 countries over
      three decades) with documented human-to-animal disease transmission were included
      in this report. FINDINGS: In these publications, 21 (38%) pathogens studied were
      bacterial, 16 (29%) were viral, 12 (21%) were parasitic, and 7 (13%) were fungal,
      other, or involved multiple pathogens. Effected animals included wildlife (n =
      28, 50%), livestock (n = 24, 43%), companion animals (n = 13, 23%), and various
      other animals or animals not explicitly mentioned (n = 2, 4%). Published reports
      of reverse zoonoses transmission occurred in every continent except Antarctica
      therefore indicating a worldwide disease threat. INTERPRETATION: As we see a
      global increase in industrial animal production, the rapid movement of humans and
      animals, and the habitats of humans and wild animals intertwining with great
      complexity, the future promises more opportunities for humans to cause reverse
      zoonoses. Scientific research must be conducted in this area to provide a richer
      understanding of emerging and reemerging disease threats. As a result,
      multidisciplinary approaches such as One Health will be needed to mitigate these
      problems.

PMID- 24586501
TI  - CCR5 conformations are dynamic and modulated by localization, trafficking and G
      protein association.
AB  - CCR5 acts as the principal coreceptor during HIV-1 transmission and early stages
      of infection. Efficient HIV-1 entry requires a series of processes, many
      dependent on the conformational state of both viral envelope protein and cellular
      receptor. Monoclonal antibodies (MAbs) are able to identify different CCR5
      conformations, allowing for their use as probes to distinguish CCR5 populations.
      Not all CCR5 MAbs are able to reduce HIV-1 infection, suggesting the use of
      select CCR5 populations for entry. In the U87.CD4.CCR5-GFP cell line, we used
      such HIV-1-restricting MAbs to probe the relation between localization,
      trafficking and G protein association for individual CCR5 conformations. We find
      that CCR5 conformations not only exhibit different localization and abundance
      patterns throughout the cell, but that they also display distinct sensitivities
      to endocytosis inhibition. Using chemokine analogs that vary in their HIV-1
      inhibitory mechanisms, we also illustrate that responses to ligand engagement are
      conformation-specific. Additionally, we provide supporting evidence for the
      select sensitivity of conformations to G protein association. Characterizing the
      link between the function and dynamics of CCR5 populations has implications for
      understanding their selective targeting by HIV-1 and for the development of
      inhibitors that will block CCR5 utilization by the virus. 

PMID- 24586502
TI  - Comparison of efficacy of intensive versus mild pitavastatin therapy on lipid and
      inflammation biomarkers in hypertensive patients with dyslipidemia.
AB  - OBJECTIVE: Intensive as compared to mild statin therapy has been proven to be
      superior in improving cardiovascular outcome, whereas the effects of intensive
      statin therapy on inflammation and lipoprotein biomarkers are not well defined.
      METHODS: This study assigned essential hypertensive patients with dyslipidemia to
      6 months administration of mild (1 mg/day, n = 34) or intensive pitavastatin
      therapy (4 mg/day, n = 29), and various lipid and inflammation biomarkers were
      measured at baseline, and 3 and 6 months after the start of treatment. RESULTS:
      Both pitavastatin doses were well tolerated, and there were no serious treatment
      related adverse events. After 6 months, significant improvements in total
      cholesterol, triglycerides, low-density lipoprotein (LDL-) cholesterol, LDL/high
      density lipoprotein cholesterol (LDL/HDL), apolipoproteins B, C-II, and E,
      apolipoprotein-B/apolipoprotein-A-I (Apo B/Apo A-I), and malondialdehyde (MDA-)
      LDL were observed in both groups. Compared with the mild pitavastatin group, the
      intensive pitavastatin therapy showed significantly greater decreases in C
      reactive protein (F = 3.76, p<0.05), total cholesterol (F = 10.65), LDL
      cholesterol (F = 23.37), LDL/HDL (F = 12.34), apolipoproteins B (F = 19.07) and E
      (F = 6.49), Apo B/Apo A-I (F = 13.26), and MDA-LDL (F = 5.76) (p<0.01,
      respectively). CONCLUSION: Intensive pitavastatin therapy may have a more
      favorable effect not only in decreasing LDL-cholesterol but also in pleiotropic
      benefits in terms of improvement of apolipoproteins, inflammation, or oxidation.

PMID- 24586503
TI  - Ecological correlates of group-size variation in a resource-defense ungulate, the
      sedentary guanaco.
AB  - For large herbivores, predation-risk, habitat structure and population density
      are often reported as major determinants of group size variation within and
      between species. However, whether the underlying causes of these relationships
      imply an ecological adaptation or are the result of a purely mechanistic process
      in which fusion and fragmentation events only depend on the rate of group
      meeting, is still under debate. The aim of this study was to model guanaco family
      and bachelor group sizes in contrasting ecological settings in order to test
      hypotheses regarding the adaptive significance of group-size variation. We
      surveyed guanaco group sizes within three wildlife reserves located in eastern
      Patagonia where guanacos occupy a mosaic of grasslands and shrublands. Two of
      these reserves have been free from predators for decades while in the third,
      pumas often prey on guanacos. All locations have experienced important changes in
      guanaco abundance throughout the study offering the opportunity to test for
      density effects. We found that bachelor group size increased with increasing
      density, as expected by the mechanistic approach, but was independent of habitat
      structure or predation risk. In contrast, the smaller and territorial family
      groups were larger in the predator-exposed than in the predator-free locations,
      and were larger in open grasslands than in shrublands. However, the influence of
      population density on these social units was very weak. Therefore, family group
      data supported the adaptive significance of group-size variation but did not
      support the mechanistic idea. Yet, the magnitude of the effects was small and
      between-population variation in family group size after controlling for habitat
      and predation was negligible, suggesting that plasticity of these social units is
      considerably low. Our results showed that different social units might respond
      differentially to local ecological conditions, supporting two contrasting
      hypotheses in a single species, and highlight the importance of taking into
      account the proximate interests and constraints to which group members may be
      exposed to when deriving predictions about group-size variation. 

PMID- 24586504
TI  - Selective activation of hTRPV1 by N-geranyl cyclopropylcarboxamide, an amiloride
      insensitive salt taste enhancer.
AB  - TRPV1t, a variant of the transient receptor potential vanilloid-1 (TRPV1) has
      been proposed as a constitutively active, non-selective cation channel as a
      putative amiloride-insensitive salt taste receptor and shares many properties
      with TRPV1. Based on our previous chorda tympani taste nerve recordings in
      rodents and human sensory evaluations, we proposed that N
      geranylcyclopropylcarboxamide (NGCC), a novel synthetic compound, acts as a salt
      taste enhancer by modulating the amiloride/benzamil-insensitive Na(+) entry
      pathways. As an extension of this work, we investigated NGCC-induced human TRPV1
      (hTRPV1) activation using a Ca(2+)-flux signaling assay in cultured cells. NGCC
      enhanced Ca(2+) influx in hTRPV1-expressing cells in a dose-dependent manner
      (EC50 = 115 uM). NGCC-induced Ca(2+) influx was significantly attenuated by
      ruthenium red (RR; 30 uM), a non-specific blocker of TRP channels and capsazepine
      (CZP; 5 uM), a specific antagonist of TRPV1, implying that NGCC directly
      activates hTRPV1. TRPA1 is often co-expressed with TRPV1 in sensory neurons.
      Therefore, we also investigated the effects of NGCC on hTRPA1-expressing cells.
      Similar to hTRPV1, NGCC enhanced Ca(2+) influx in hTRPA1-expressing cells (EC50 =
      83.65 uM). The NGCC-induced Ca(2+) influx in hTRPA1-expressing cells was blocked
      by RR (30 uM) and HC-030031 (100 uM), a specific antagonist of TRPA1. These
      results suggested that NGCC selectively activates TRPV1 and TRPA1 in cultured
      cells. These data may provide additional support for our previous hypothesis that
      NGCC interacts with TRPV1 variant cation channel, a putative amiloride/benzamil
      insensitive salt taste pathway in the anterior taste receptive field.

PMID- 24586505
TI  - A comparison of the functional traits of common reed (Phragmites australis) in
      northern China: aquatic vs. terrestrial ecotypes.
AB  - Common reed (Phragmites australis (Cav.) Trin. ex Steud.) is distributed widely
      throughout the world with various ecotypes. This research compares the functional
      traits and biomass allocation patterns of two contrasting reed ecotypes. Twelve
      pairs of aquatic and terrestrial reed samples were collected in northern China.
      Significant differences in functional traits between the two reed ecotypes were
      observed, while biomass allocation patterns of reed organs did not differ
      significantly except for at the root. The dry matter content (DMC) in the whole
      of the reed plant, leaf, root, and rhizome was higher; while the specific leaf
      area (SLA) and specific root length (SRL) were lower in terrestrial versus
      aquatic reed. The biomass allocation in organs of the two forms of reed was
      isometric, only root in the terrestrial habitat increased faster with an increase
      in the whole plant biomass. It can be affirmed that aquatic and terrestrial reed
      that adapt to different environments generally has distinct leaf and root
      functional traits but isometric biomass allocation patterns. This suggests
      different resource acquisition strategies: (1) aquatic reed grows faster with
      high SLA and SRL and is more responsive to the environment, while (2) terrestrial
      reed with high DMC grows slower and is less responsive to the adverse environment
      (e.g. dry soil conditions). 

PMID- 24586507
TI  - Robustness of controllability for networks based on edge-attack.
AB  - We study the controllability of networks in the process of cascading failures
      under two different attacking strategies, random and intentional attack,
      respectively. For the highest-load edge attack, it is found that the
      controllability of Erdos-Renyi network, that with moderate average degree, is
      less robust, whereas the Scale-free network with moderate power-law exponent
      shows strong robustness of controllability under the same attack strategy. The
      vulnerability of controllability under random and intentional attacks behave
      differently with the increasing of removal fraction, especially, we find that the
      robustness of control has important role in cascades for large removal fraction.
      The simulation results show that for Scale-free networks with various power-law
      exponents, the network has larger scale of cascades do not mean that there will
      be more increments of driver nodes. Meanwhile, the number of driver nodes in
      cascading failures is also related to the edges amount in strongly connected
      components. 

PMID- 24586506
TI  - MicroRNA-206: a potential circulating biomarker candidate for amyotrophic lateral
      sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is a lethal motor neuron disease that
      progressively debilitates neuronal cells that control voluntary muscle activity.
      Biomarkers are urgently needed to facilitate ALS diagnosis and prognosis, and as
      indicators of therapeutic response in clinical trials. microRNAs (miRNAs), small
      posttranscriptional modifiers of gene expression, are frequently altered in
      disease conditions. Besides their important regulatory role in variety of
      biological processes, miRNAs can also be released into the circulation by
      pathologically affected tissues and display remarkable stability in body fluids.
      In a mouse model of ALS that expresses mutated human superoxide dismutase 1 (SOD1
      G93A) skeletal muscle is one of the tissues affected early by mutant SOD1
      toxicity. To find biomarkers for ALS, we studied miRNA alterations from skeletal
      muscle and plasma of SOD1-G93A mice, and subsequently tested the levels of the
      affected miRNAs in the serum from human ALS patients. Fast-twitch and slow-twitch
      muscles from symptomatic SOD1-G93A mice (age 90 days) and their control
      littermates were first studied using miRNA microarrays and then evaluated with
      quantitative PCR from five age groups from neonatal to the terminal disease stage
      (10-120 days). Among those miRNA changed in various age/gender/muscle groups (miR
      206, -1, -133a, -133b, -145, -21, -24), miR-206 was the only one consistently
      altered during the course of the disease pathology. In both sexes, mature miR-206
      was increased in fast-twitch muscles preferably affected in the SOD1-G93A model,
      with highest expression towards the most severely affected animals. Importantly,
      miR-206 was also increased in the circulation of symptomatic animals and in a
      group of 12 definite ALS patients tested. We conclude that miR-206 is elevated in
      the circulation of symptomatic SOD1-G93A mice and possibly in human ALS patients.
      Although larger scale studies on ALS patients are warranted, miR-206 is a
      promising candidate biomarker for this motor neuron disease. 

PMID- 24586508
TI  - Photoinhibition-like damage to the photosynthetic apparatus in plant leaves
      induced by submergence treatment in the dark.
AB  - Submergence is a common type of environmental stress for plants. It hampers
      survival and decreases crop yield, mainly by inhibiting plant photosynthesis. The
      inhibition of photosynthesis and photochemical efficiency by submergence is
      primarily due to leaf senescence and excess excitation energy, caused by signals
      from hypoxic roots and inhibition of gas exchange, respectively. However, the
      influence of mere leaf-submergence on the photosynthetic apparatus is currently
      unknown. Therefore, we studied the photosynthetic apparatus in detached leaves
      from four plant species under dark-submergence treatment (DST), without influence
      from roots and light. Results showed that the donor and acceptor sides, the
      reaction center of photosystem II (PSII) and photosystem I (PSI) in leaves were
      significantly damaged after 36 h of DST. This is a photoinhibition-like
      phenomenon similar to the photoinhibition induced by high light, as further
      indicated by the degradation of PsaA and D1, the core proteins of PSI and PSII.
      In contrast to previous research, the chlorophyll content remained unchanged and
      the H2O2 concentration did not increase in the leaves, implying that the damage
      to the photosynthetic apparatus was not caused by senescence or over-accumulation
      of reactive oxygen species (ROS). DST-induced damage to the photosynthetic
      apparatus was aggravated by increasing treatment temperature. This type of damage
      also occurred in the anaerobic environment (N2) without water, and could be
      eliminated or restored by supplying air to the water during or after DST. Our
      results demonstrate that DST-induced damage was caused by the hypoxic
      environment. The mechanism by which DST induces the photoinhibition-like damage
      is discussed below. 

PMID- 24586509
TI  - Role of CXCR3/CXCL10 axis in immune cell recruitment into the small intestine in
      celiac disease.
AB  - Lymphocytic infiltration in the lamina propria (LP), which is primarily composed
      of CD4(+) Th1 cells and plasma cells, and increased numbers of intraepithelial
      lymphocytes (IELs), is a characteristic finding in active celiac disease (CD).
      Signals for this selective cell recruitment have not been fully established.
      CXCR3 and its ligands, particularly CXCL10, have been suggested to be one of the
      most relevant pathways in the attraction of cells into inflamed tissues. In
      addition, CXCR3 is characteristically expressed by Th1 cells. The aim of this
      work was to investigate the participation of the chemokine CXCL10/CXCR3 axis in
      CD pathogenesis. A higher concentration of CXCL10 was found in the serum of
      untreated CD patients. The mRNA levels of CXCL10 and CXCL11 but not CXCL9 were
      significantly higher in duodenal biopsies from untreated CD patients compared
      with non-CD controls or treated patients. The results demonstrate that CXCL10 is
      abundantly produced in untreated CD and reduced in treated patients, and the
      expression of CXCL10 was found to be correlated with the IFNgamma levels in the
      tissue. Plasma cells and enterocytes were identified as CXCL10-producing cells.
      Moreover, the CXCL10 expression in intestinal tissues was upregulated by poly I:C
      and IL-15. IELs, LP T lymphocytes, and plasma cells, which infiltrate the
      intestinal mucosa in untreated CD, express CXCR3. The CXCR3/CXCL10 signalling
      axis is overactivated in the small intestinal mucosa in untreated patients, and
      this finding explains the specific recruitment of the major cell populations that
      infiltrate the epithelium and the LP in CD.

PMID- 24586510
TI  - The relationship between BCMO1 gene variants and macular pigment optical density
      in persons with and without age-related macular degeneration.
AB  - BACKGROUND: Recent evidence indicates that gene variants related to carotenoid
      metabolism play a role in the uptake of macular pigments lutein (L) and
      zeaxanthin (Z). Moreover, these pigments are proposed to reduce the risk for
      advanced age-related macular degeneration (AMD). This study provides the initial
      examination of the relationship between the gene variants related to carotenoid
      metabolism, macular pigment optical density (MPOD) and their combined expression
      in healthy humans and patients with AMD. PARTICIPANTS AND METHODS: Forty-four
      participants were enrolled from a general population and a private practice
      including 20 healthy participants and 24 patients with advanced (neovascular)
      AMD. Participants were genotyped for the three single nucleotide polymorphisms
      (SNPs) upstream from BCMO1, rs11645428, rs6420424 and rs6564851 that have been
      shown to either up or down regulate beta-carotene conversion efficiency in the
      plasma. MPOD was determined by heterochromatic flicker photometry. RESULTS:
      Healthy participants with the rs11645428 GG genotype, rs6420424 AA genotype and
      rs6564851 GG genotype all had on average significantly lower MPOD compared to
      those with the other genotypes (p<0.01 for all three comparisons). When combining
      BCMO1 genotypes reported to have "high" (rs11645428 AA/rs6420424 GG/rs6564851 TT)
      and "low" (rs11645428 GG/rs6420424 AA/rs6564851 GG) beta-carotene conversion
      efficiency, we demonstrate clear differences in MPOD values (p<0.01). In patients
      with AMD there were no significant differences in MPOD for any of the three BCMO1
      gene variants. CONCLUSION: In healthy participants MPOD levels can be related to
      high and low beta-carotene conversion BCMO1 genotypes. Such relationships were
      not found in patients with advanced neovascular AMD, indicative of additional
      processes influencing carotenoid uptake, possibly related to other AMD
      susceptibility genes. Our findings indicate that specific BCMO1 SNPs should be
      determined when assessing the effects of carotenoid supplementation on macular
      pigment and that their expression may be influenced by retinal disease.

PMID- 24586511
TI  - Fast, multi-dimensional and simultaneous kymograph-like particle dynamics
      (SkyPad) analysis.
AB  - BACKGROUND: Kymograph analysis is a method widely used by researchers to analyze
      particle dynamics in one dimensional (1D) trajectories. RESULTS: Here we provide
      a Visual Basic-coded algorithm to use as a Microsoft Excel add-in that
      automatically analyzes particles in 2D trajectories with all the advantages of
      kymograph analysis. CONCLUSIONS: This add-in, which we named SkyPad, leads to
      significant time saving and higher accuracy of particle analysis. Finally, SkyPad
      can also be used for 3D trajectories analysis.

PMID- 24586512
TI  - Zonisamide attenuates alpha-synuclein neurotoxicity by an aggregation-independent
      mechanism in a rat model of familial Parkinson's disease.
AB  - The anti-epileptic agent zonisamide (ZNS) has been shown to exert protective
      effects in neurotoxin-based mouse models of Parkinson disease. However, it is
      unknown whether ZNS can attenuate toxicity of familial Parkinson's disease
      causing gene products. In this study, we investigated the effects of ZNS on
      neurodegeneration induced by expression of A53T alpha-synuclein in the rat
      substantia nigra using a recombinant adeno-associated virus vector. Expression of
      A53T alpha-synuclein yielded severe loss of nigral dopamine neurons and striatal
      dopamine nerve terminals from 2 weeks to 4 weeks after viral injection. Oral
      administration of ZNS (40 mg/kg/day) significantly delayed the pace of
      degeneration at 4 weeks after viral injection as compared with the vehicle group.
      This effect lasted until 8 weeks after viral injection, the final point of
      observation. ZNS treatment had no impact on the survival of nigrostriatal
      dopamine neurons in rats expressing green fluorescent protein. Quantification of
      striatal Ser129-phosphorylated alpha-synuclein-positive aggregates showed that
      these aggregates rapidly formed from 2 weeks to 4 weeks after viral injection.
      This increase was closely correlated with loss of nigrostriatal dopamine neurons.
      However, ZNS treatment failed to alter the number of all striatal Ser129
      phosphorylated alpha-synuclein-positive aggregates, including small dot-like and
      large round structures. The number of these aggregates was almost constant at 4
      weeks and 8 weeks after viral injection, although ZNS persistently prevented loss
      of nigrostriatal dopamine neurons during this period. Also, ZNS treatment did not
      affect the number of striatal aggregates larger than 10 um in diameter. These
      data show that ZNS attenuates alpha-synuclein-induced toxicity in a manner that
      is independent of the formation and maturation of alpha-synuclein aggregates in
      an in vivo model of familial Parkinson's disease, suggesting that ZNS may protect
      nigrostriatal dopamine neurons by modulating cellular damage or a cell death
      pathway commonly caused by neurotoxins and alpha-synuclein.

PMID- 24586513
TI  - Factors associated with exclusive breastfeeding of preterm infants. Results from
      a prospective national cohort study.
AB  - BACKGROUND AND AIM: Evidence-based knowledge of how to guide the mothers of
      preterm infants in breastfeeding establishment is contradictive or sparse. The
      aim was to investigate the associations between pre-specified clinical practices
      for facilitating breastfeeding, and exclusive breastfeeding at discharge as well
      as adequate duration thereof. METHODS: A prospective survey based on
      questionnaires was conducted with a Danish national cohort, comprised of 1,221
      mothers and their 1,488 preterm infants with a gestational age of 24-36 weeks.
      Adjusted for covariates, the pre-specified clinical practices were analysed by
      multiple logistic regression analyses. RESULTS: At discharge 68% of the preterm
      infants were exclusively breastfed and 17% partially. Test-weighing the infant,
      and minimizing the use of a pacifier, showed a protective effect to exclusive
      breastfeeding at discharge (OR 0.6 (95% CI 0.4-0.8) and 0.4 (95% CI 0.3-0.6),
      respectively). The use of nipple shields (OR 2.3 (95% CI 1.6-3.2)) and the
      initiation of breast milk expression later than 48 hours postpartum (OR 4.9 (95%
      CI 1.9-12.6)) were associated with failure of exclusive breastfeeding at
      discharge. The clinical practices associated with an inadequate breastfeeding
      duration were the initiation of breast milk expression at 12-24 hours (OR 1.6
      (95% CI 1.0-2.4)) and 24-48 hours (OR 1.8 (95% CI 1.0-3.1)) vs. before six hours
      postpartum, and the use of nipple shields (OR 1.4 (95% CI 1.1-1.9)). CONCLUSION:
      Early initiation of breast milk pumping before 12 hours postpartum may increase
      breastfeeding rates, and it seems that the use of nipple shields should be
      restricted. The use of test-weighing and minimizing the use of a pacifier may
      promote the establishment of exclusive breastfeeding, but more research is needed
      regarding adequate support to the mother when test-weighing is ceased, as more of
      these mothers ceased exclusive breastfeeding at an early stage after discharge.

PMID- 24586514
TI  - Combining the ABL1 kinase inhibitor ponatinib and the histone deacetylase
      inhibitor vorinostat: a potential treatment for BCR-ABL-positive leukemia.
AB  - Resistance to imatinib (Gleevec(r)) in cancer cells is frequently because of
      acquired point mutations in the kinase domain of BCR-ABL. Ponatinib, also known
      as AP24534, is an oral multi-targeted tyrosine kinase inhibitor (TKI), and it has
      been investigated in a pivotal phase 2 clinical trial. The histone deacetylase
      inhibitor vorinostat (suberoylanilide hydroxamic acid) has been evaluated for its
      significant clinical activity in hematological malignancies. Thus, treatments
      combining ABL TKIs with additional drugs may be a promising strategy in the
      treatment of leukemia. In the current study, we analyzed the efficacy of
      ponatinib and vorinostat treatment by using BCR-ABL-positive cell lines.
      Treatment with ponatinib for 72 h inhibited cell growth and induced apoptosis in
      K562 cells in a dose-dependent manner. We found that ponatinib potently inhibited
      the growth of Ba/F3 cells ectopically expressing BCR-ABL T315I mutation. Upon BCR
      ABL phosphorylation, Crk-L was decreased, and poly (ADP-ribose) polymerase (PARP)
      was activated in a dose-dependent manner. Combined treatment of Ba/F3 T315I
      mutant cells with vorinostat and ponatinib resulted in significantly increased
      cytotoxicity. Additionally, the intracellular signaling of ponatinib and
      vorinostat was examined. Caspase 3 and PARP activation increased after
      combination treatment with ponatinib and vorinostat. Moreover, an increase in the
      phosphorylation levels of gammaH2A.X was observed. Previously established
      ponatinib-resistant Ba/F3 cells were also resistant to imatinib, nilotinib, and
      dasatinib. We investigated the difference in the efficacy of ponatinib and
      vorinostat by using ponatinib-resistant Ba/F3 cells. Combined treatment of
      ponatinib-resistant cells with ponatinib and vorinostat caused a significant
      increase in cytotoxicity. Thus, combined administration of ponatinib and
      vorinostat may be a powerful strategy against BCR-ABL mutant cells and could
      enhance the cytotoxic effects of ponatinib in those BCR-ABL mutant cells. 

PMID- 24586515
TI  - The efficacy of radiofrequency ablation combined with transcatheter arterial
      chemoembolization for primary hepatocellular carcinoma in a cohort of 487
      patients.
AB  - Although diagnostic methods, surgical techniques, and perioperative care have
      undergone significant advancement over the past decades, the prognosis of primary
      hepatocellular carcinoma (HCC) remains discouraged because of the high
      postoperative recurrence rate and high cancer mortality. Radiofrequency ablation
      (RFA) combined with transcatheter arterial chemoembolization (TACE) is a recently
      developed means for the treatment of HCC. In this study, we analyzed the efficacy
      of RFA plus TACE in 487 cases of HCC in our institution. We observed that the 1-,
      2-, 3-, 4- and 5-year rates of overall survival rates after RFA and TACE
      treatment were 97.5% (475/487), 89.4% (277/310), 84.2% (181/215), 80.4% (150/186)
      and 78.7% (141/177), respectively. We did not find that age or tumor location
      (the caudate group or non-caudate group) plays a role in this cohort. However, we
      have identified that tumor recurrent status, the number of tumors, albumin (ALB),
      prothrombin time (PT) and platelet count (PLT) were significantly associated with
      poor overall survival in HCC patients receiving RFA combined with TACE.
      Interestingly, tumor size did not significantly impact overall survival,
      indicating that RFA combined with TACE for HCC treatment has the same efficiency
      for different sizes of tumors. Our results provide evidence for the rationale for
      using combined RFA and TACE in the treatment of primary HCC. 

PMID- 24586516
TI  - Infrastructure and contamination of the physical environment in three Bangladeshi
      hospitals: putting infection control into context.
AB  - OBJECTIVE: This paper describes the physical structure and environmental
      contamination in selected hospital wards in three government hospitals in
      Bangladesh. METHODS: The qualitative research team conducted 48 hours of
      observation in six wards from three Bangladeshi tertiary hospitals in 2007. They
      recorded environmental contamination with body secretions and excretions and
      medical waste and observed ward occupant handwashing and use of personal
      protective equipment. They recorded number of persons, number of open doors and
      windows, and use of fans. They measured the ward area and informally observed
      waste disposal outside the wards. They conducted nine focus group discussions
      with doctors, nurses and support staff. RESULTS: A median of 3.7 persons were
      present per 10 m(2) of floor space in the wards. A median of 4.9 uncovered coughs
      or sneezes were recorded per 10 m(2) per hour per ward. Floors in the wards were
      soiled with saliva, spit, mucous, vomitus, feces and blood 125 times in 48 hours.
      Only two of the 12 patient handwashing stations had running water and none had
      soap. No disinfection was observed before or after using medical instruments.
      Used medical supplies were often discarded in open containers under the beds.
      Handwashing with soap was observed in only 32 of 3,373 handwashing opportunities
      noted during 48 hours. Mosquitoes and feral cats were commonly observed in the
      wards. CONCLUSIONS: The physical structure and environment of our study hospitals
      are conducive to the spread of infection to people in the wards. Low-cost
      interventions on hand hygiene and cleaning procedures for rooms and medical
      equipment should be developed and evaluated for their practicality and
      effectiveness.

PMID- 24586517
TI  - Exacerbation of celecoxib-induced renal injury by concomitant administration of
      misoprostol in rats.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) can produce adverse effects by
      inhibiting prostaglandin (PG) synthesis. A PGE1 analogue, misoprostol, is often
      utilized to alleviate NSAID-related gastrointestinal side effects. This study
      examined the effect of misoprostol on celecoxib renal toxicity. Additionally, the
      effects of these drugs on cardiovascular parameters were evaluated. Four
      randomized rat groups were orally gavaged for 9 days, two groups receiving
      vehicle and two groups receiving misoprostol (100 ug/kg) twice daily. Celecoxib
      (40 mg/kg) was co-administered once daily to one vehicle and one misoprostol
      group from days 3 to 9. Urine and blood samples were collected and blood pressure
      parameters were measured during the study period. Hearts and kidneys were
      harvested on final day. Day 2 urinary electrolyte samples revealed significant
      reductions in sodium excretion in misoprostol (0.12 +/- 0.05 umol/min/100 g) and
      misoprostol+celecoxib groups (0.07 +/- 0.02 umol/min/100 g). At day 3, all
      treatment groups showed significantly reduced sodium excretion. Potassium
      excretion diminished significantly in vehicle+celecoxib and misoprostol+celecoxib
      groups from day 3 onward. Urinary kidney injury molecule-1 levels were
      significantly increased in vehicle+celecoxib (0.65 +/- 0.02 vs. 0.35 +/- 0.07
      ng/mL, p = 0.0002) and misoprostol+celecoxib (0.61 +/- 0.06 vs. 0.37 +/- 0.06
      ng/mL, p = 0.0015) groups when compared to baseline; while plasma levels of
      cardiac troponin I increased significantly in vehicle+celecoxib (p = 0.0040) and
      misoprostol+misoprostol (p = 0.0078) groups when compared to vehicle+vehicle.
      Blood pressure parameters increased significantly in all misoprostol treated
      groups. Significant elevation in diastolic (p = 0.0071) and mean blood pressure
      (p = 0.0153) was noted in misoprostol+celecoxib compared to vehicle+celecoxib.
      All treatments produced significant tubular dilatation/necrosis compared to
      control. No significant myocardial changes were noticed; however, three animals
      presented with pericarditis. Kidney, heart, and plasma celecoxib levels revealed
      no significant change between vehicle+celecoxib and misoprostol+celecoxib.
      Concomitant misoprostol administration did not prevent celecoxib renal toxicity,
      and instead exacerbated renal side effects. Misoprostol did not alter plasma or
      tissue celecoxib concentrations suggesting no pharmacokinetic interaction between
      celecoxib and misoprostol.

PMID- 24586518
TI  - Effects of switching from stavudine to raltegravir on subcutaneous adipose tissue
      in HIV-infected patients with HIV/HAART-associated lipodystrophy syndrome (HALS).
      A clinical and molecular study.
AB  - HIV-1/HAART-associated lipodystrophy syndrome (HALS) has been associated with
      exposure to stavudine (d4T) through mitochondrial dysfunction. We performed a 48
      week study to assess the effects of switching from d4T to raltegravir (RAL) on
      metabolic and fat molecular parameters of patients with HALS. Forty-two patients
      with HALS and a median exposure to d4T > 7 years were switched to RAL and
      followed for 48 weeks. Fasting metabolic tests, HIV RNA, CD4 cell count, and fat
      measured by DEXA were obtained at baseline and week 48. mtDNA and gene
      transcripts for PPAR gamma, adiponectin, cytochrome b, Cox IV, TNF alpha, MCP-1
      and CD68 were assessed in paired subcutaneous fat tissue biopsies. Lipid
      parameters, fasting glucose, insulin, and HOMA-IR did not change significantly.
      Whole body fat (P = 0.0027) and limb fat mass (P<0.0001) increased from baseline.
      Trunk/limb fat ratio (P = 0.0022), fat mass ratio (P = 0.0020), fat mass index (P
      = 0.0011) and percent leg fat normalized to BMI (P<0.0001) improved after 48
      weeks. Relative abundance of mtDNA, expression of PPAR gamma, adiponectin, Cyt b,
      and MCP-1 genes increased, whereas Cox IV, TNF alpha, and CD68 did not change
      significantly from baseline. Switching from d4T to RAL in patients with HALS is
      associated with an increase in limb fat mass and an improvement in markers of
      adipocyte differentiation and mitochondrial function in SAT. 

PMID- 24586520
TI  - Quantification of health by scaling similarity judgments.
AB  - OBJECTIVE: A new methodology is introduced to scale health states on an interval
      scale based on similarity responses. It could be well suited for valuation of
      health states on specific regions of the health continuum that are problematic
      when applying conventional valuation techniques. These regions are the top-end,
      bottom-end, and states around 'dead'. METHODS: Three samples of approximately 500
      respondents were recruited via an online survey. Each sample received a different
      judgmental task in which similarity data were elicited for the top seven health
      states in the dementia quality of life instrument (DQI). These states were
      '111111' (no problems on any domain) and six others with some problems (level 2)
      on one domain. The tasks presented two (dyads), three (triads), or four (quads)
      DQI health states. Similarity data were transformed into interval-level scales
      with metric and non-metric multidimensional scaling algorithms. The three
      response tasks were assessed for their feasibility and comprehension. RESULTS: In
      total 532, 469, and 509 respondents participated in the dyads, triads, and quads
      tasks respectively. After the scaling procedure, in all three response tasks, the
      best health state '111111' was positioned at one end of the health-state
      continuum and state '111211' was positioned at the other. The correlation between
      the metric scales ranged from 0.73 to 0.95, while the non-metric scales ranged
      from 0.76 to 1.00, indicating strong to near perfect associations. There were no
      apparent differences in the reported difficulty of the response tasks, but the
      triads had the highest number of drop-outs. DISCUSSION: Multidimensional scaling
      proved to be a feasible method to scale health-state similarity data. The dyads
      and especially the quads response tasks warrant further investigation, as these
      tasks provided the best indications of respondent comprehension.

PMID- 24586519
TI  - Determinants of suicide and accidental or violent death in the Australian HIV
      Observational Database.
AB  - BACKGROUND: Rates of suicide and accidental or violent death remain high in HIV
      positive populations despite significantly improved prognosis since the
      introduction of cART. METHODS: We conducted a nested case-control study of
      suicide and accidental or violent death in the Australian HIV Observational
      Database (AHOD) between January 1999 and March 2012. For each case, 2 controls
      were matched by clinic, age, sex, mode of exposure and HIV-positive date to
      adjust for potential confounding by these covariates. Risk of suicide and
      accidental or violent death was estimated using conditional logistic regression.
      RESULTS: We included 27 cases (17 suicide and 10 violent/accidental death) and 54
      controls. All cases were men who have sex with men (MSM) or MSM/ injecting drug
      use (IDU) mode of exposure. Increased risk was associated with unemployment (Odds
      Ratio (OR) 5.86, 95% CI: 1.69-20.37), living alone (OR 3.26, 95% CI: 1.06-10.07),
      suicidal ideation (OR 6.55, 95% CI: 1.70-25.21), and >2 psychiatric/cognitive
      risk factors (OR 4.99, 95% CI: 1.17-30.65). CD4 cell count of >500 cells/uL (OR
      0.25, 95% CI: 0.07-0.87) and HIV-positive date >=1990 (1990-1999 (OR 0.31, 95%
      CI: 0.11-0.89), post-2000 (OR 0.08, 95% CI: 0.01-0.84)) were associated with
      decreased risk. CD4 cell count >=500 cells/uL remained a significant predictor of
      reduced risk (OR 0.15, 95% CI: 0.03-0.70) in a multivariate model adjusted for
      employment status, accommodation status and HIV-positive date. CONCLUSIONS: After
      adjustment for psychosocial factors, the immunological status of HIV-positive
      patients contributed to the risk of suicide and accidental or violent death. The
      number of psychiatric/cognitive diagnoses contributed to the level of risk but
      many psychosocial factors were not individually significant. These findings
      indicate a complex interplay of factors associated with risk of suicide and
      accidental or violent death.

PMID- 24586522
TI  - Could dromedary camels develop stereotypy? The first description of stereotypical
      behaviour in housed male dromedary camels and how it is affected by different
      management systems.
AB  - Dromedary camel husbandry has recently been evolving towards a semi-intensive
      system, due to the changes in use of the animal and the settlement of nomadic
      populations. Captivity could restrict its social activities, limiting the
      expression of various behavioural needs and causing the manifestation of
      stereotypy. The aims of this trial were, firstly, to identify and describe some
      stereotypical behaviours in captive male dromedary camels used for artificial
      insemination and, secondly, to study the effects on them of the following
      husbandry management systems: i) housing in single boxes for 24 hours (H24), ii)
      housing in single boxes for 23 hours with one hour free in the paddock (H23), and
      iii) housing in single boxes for 22 hours 30 min with 1 h of paddock time and 30
      min exposure to a female camel herd (ExF). Every day, the camels were filmed in
      their single box in the morning for 30 minutes to record their behavioural
      activities and a focal animal sampling ethogram was filled in. In this study,
      male camels showed both oral and locomotor stereotypy most frequently when the
      bulls were reared in H24. Overall, this preliminary study is a starting point in
      the identification of stereotypies in male camels, reporting the positive effects
      of spending one hour outdoor and of social interaction with females. 

PMID- 24586521
TI  - The dichotomous pattern of IL-12r and IL-23R expression elucidates the role of IL
      12 and IL-23 in inflammation.
AB  - IL-12 and IL-23 cytokines respectively drive Th1 and Th17 type responses. Yet,
      little is known regarding the biology of these receptors. As the IL-12 and IL-23
      receptors share a common subunit, it has been assumed that these receptors are co
      expressed. Surprisingly, we find that the expression of each of these receptors
      is restricted to specific cell types, in both mouse and human. Indeed, although
      IL-12Rbeta2 is expressed by NK cells and a subset of gammadelta T cells, the
      expression of IL-23R is restricted to specific T cell subsets, a small number of
      B cells and innate lymphoid cells. By exploiting an IL-12- and IL-23-dependent
      mouse model of innate inflammation, we demonstrate an intricate interplay between
      IL-12Rbeta2 NK cells and IL-23R innate lymphoid cells with respectively dominant
      roles in the regulation of systemic versus local inflammatory responses.
      Together, these findings support an unforeseen lineage-specific dichotomy in the
      in vivo role of both the IL-12 and IL-23 pathways in pathological inflammatory
      states, which may allow more accurate dissection of the roles of these receptors
      in chronic inflammatory diseases in humans. 

PMID- 24586523
TI  - CFTR mutations spectrum and the efficiency of molecular diagnostics in Polish
      cystic fibrosis patients.
AB  - Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane
      regulator gene (CFTR). In light of the strong allelic heterogeneity and regional
      specificity of the mutation spectrum, the strategy of molecular diagnostics and
      counseling in CF requires genetic tests to reflect the frequency profile
      characteristic for a given population. The goal of the study was to provide an
      updated comprehensive estimation of the distribution of CFTR mutations in Polish
      CF patients and to assess the effectiveness of INNOLiPA_CFTR tests in Polish
      population. The analyzed cohort consisted of 738 patients with the clinically
      confirmed CF diagnosis, prescreened for molecular defects using INNOLiPA_CFTR
      panels from Innogenetics. A combined efficiency of INNOLiPA CFTR_19 and
      CFTR_17_TnUpdate tests was 75.5%; both mutations were detected in 68.2%, and one
      mutation in 14.8% of the affected individuals. The group composed of all the
      patients with only one or with no mutation detected (109 and 126 individuals,
      respectively) was analyzed further using a mutation screening approach, i.e.
      SSCP/HD (single strand conformational polymorphism/heteroduplex) analysis of PCR
      products followed by sequencing of the coding sequence. As a result, 53 more
      mutations were found in 97 patients. The overall efficiency of the CF allele
      detection was 82.5% (7.0% increase compared to INNOLiPA tests alone). The
      distribution of the most frequent mutations in Poland was assessed. Most of the
      mutations repetitively found in Polish patients had been previously described in
      other European populations. The most frequent mutated allele, F508del,
      represented 54.5% of Polish CF chromosomes. Another eight mutations had
      frequencies over 1%, 24 had frequencies between 1 and 0.1%; c.2052-2053insA and
      c.3468+2_3468+3insT were the most frequent non-INNOLiPA mutations. Mutation
      distribution described herein is also relevant to the Polish diaspora. Our study
      also demonstrates that the reported efficiency of mutation detection strongly
      depends on the diagnostic experience of referring health centers. 

PMID- 24586524
TI  - Maternal bisphenol a exposure impacts the fetal heart transcriptome.
AB  - Conditions during fetal development influence health and disease in adulthood,
      especially during critical windows of organogenesis. Fetal exposure to the
      endocrine disrupting chemical, bisphenol A (BPA) affects the development of
      multiple organ systems in rodents and monkeys. However, effects of BPA exposure
      on cardiac development have not been assessed. With evidence that maternal BPA is
      transplacentally delivered to the developing fetus, it becomes imperative to
      examine the physiological consequences of gestational exposure during primate
      development. Herein, we evaluate the effects of daily, oral BPA exposure of
      pregnant rhesus monkeys (Macaca mulatta) on the fetal heart transcriptome.
      Pregnant monkeys were given daily oral doses (400 ug/kg body weight) of BPA
      during early (50-100 +/- 2 days post conception, dpc) or late (100 +/- 2 dpc-
      term), gestation. At the end of treatment, fetal heart tissues were collected and
      chamber specific transcriptome expression was assessed using genome-wide
      microarray. Quantitative real-time PCR was conducted on select genes and
      ventricular tissue glycogen content was quantified. Our results show that BPA
      exposure alters transcription of genes that are recognized for their role in
      cardiac pathophysiologies. Importantly, myosin heavy chain, cardiac isoform alpha
      (Myh6) was down-regulated in the left ventricle, and 'A Disintegrin and
      Metalloprotease 12', long isoform (Adam12-l) was up-regulated in both ventricles,
      and the right atrium of the heart in BPA exposed fetuses. BPA induced alteration
      of these genes supports the hypothesis that exposure to BPA during fetal
      development may impact cardiovascular fitness. Our results intensify concerns
      about the role of BPA in the genesis of human metabolic and cardiovascular
      diseases.

PMID- 24586525
TI  - The association of HMGB1 gene with the prognosis of HCC.
AB  - High-mobility group box 1 protein (HMGB1) is an evolutionarily ancient and
      critical regulator of cell death and survival. HMGB1 is a chromatin-associated
      nuclear protein molecule that triggers extracellular damage. The expression of
      HMGB1 has been reported in many types of cancers, but the role of HMGB1 in hepato
      cellular carcinoma (HCC) is unknown.The aim of this study was to analyze the
      roles of HMGB1 in HCC progression using HCC clinical samples. We also
      investigated the clinical outcomes of HCC samples with a special focus on HMBG1
      expression. In an immunohistochemical study conducted on 208 cases of HCC, HMGB1
      had high expression in 134 cases(64.4%).The HMGB1 expression level did not
      correlate with any clinicopathological parameters, except alpha fetoprotein (AFP)
      (p = 0.041) and CLIP stage (p = 0.007). However, survival analysis showed that
      the group with HMBG1 overexpression had a significantly shorter overall survival
      time than the group with a down-regulated expression of HMBG1 (HR = 0.568, CI
      (0.398, 0.811), p = 0.002). Multivariate analysis showed that HMGB1 expression
      was a significant and independent prognostic parameter (HR = 0.562, CI (0.388,
      0.815), p = 0.002) for HCC patients. The ability of proliferation, migration and
      invasion of HCC cells was suppressed with the disruption of endogenous HMGB1
      using small interfering RNAs. On the other hand, the ability of proliferation,
      migration and invasion of HCC cells was strengthened when the expression
      endogenous HMGB1 was enhanced using HMGB1 DNA. HMGB1 expression may be a novel
      and independent predictor for the prognosis of HCC patients. The overexpression
      of HMGB1 in HCC could be a novel, effective, and supplementary biomarker for HCC,
      since it plays a vital role in the progression of HCC.

PMID- 24586526
TI  - Image-derived input function derived from a supervised clustering algorithm:
      methodology and validation in a clinical protocol using [11C](R)-rolipram.
AB  - Image-derived input function (IDIF) obtained by manually drawing carotid arteries
      (manual-IDIF) can be reliably used in [(11)C](R)-rolipram positron emission
      tomography (PET) scans. However, manual-IDIF is time consuming and subject to
      inter- and intra-operator variability. To overcome this limitation, we developed
      a fully automated technique for deriving IDIF with a supervised clustering
      algorithm (SVCA). To validate this technique, 25 healthy controls and 26 patients
      with moderate to severe major depressive disorder (MDD) underwent T1-weighted
      brain magnetic resonance imaging (MRI) and a 90-minute [(11)C](R)-rolipram PET
      scan. For each subject, metabolite-corrected input function was measured from the
      radial artery. SVCA templates were obtained from 10 additional healthy subjects
      who underwent the same MRI and PET procedures. Cluster-IDIF was obtained as
      follows: 1) template mask images were created for carotid and surrounding tissue;
      2) parametric image of weights for blood were created using SVCA; 3) mask images
      to the individual PET image were inversely normalized; 4) carotid and surrounding
      tissue time activity curves (TACs) were obtained from weighted and unweighted
      averages of each voxel activity in each mask, respectively; 5) partial volume
      effects and radiometabolites were corrected using individual arterial data at
      four points. Logan-distribution volume (V T/f P) values obtained by cluster-IDIF
      were similar to reference results obtained using arterial data, as well as those
      obtained using manual-IDIF; 39 of 51 subjects had a V T/f P error of <5%, and
      only one had error >10%. With automatic voxel selection, cluster-IDIF curves were
      less noisy than manual-IDIF and free of operator-related variability. Cluster
      IDIF showed widespread decrease of about 20% [(11)C](R)-rolipram binding in the
      MDD group. Taken together, the results suggest that cluster-IDIF is a good
      alternative to full arterial input function for estimating Logan-V T/f P in
      [(11)C](R)-rolipram PET clinical scans. This technique enables fully automated
      extraction of IDIF and can be applied to other radiotracers with similar
      kinetics. 

PMID- 24586527
TI  - Pediatric malignancies, treatment outcomes and abandonment of pediatric cancer
      treatment in Zambia.
AB  - BACKGROUND: There exist significant challenges to the receipt of comprehensive
      oncologic treatment for children diagnosed with cancer in sub-Saharan Africa. To
      better define those challenges, we investigated treatment outcomes and risk
      factors for treatment abandonment in a cohort of children diagnosed with cancer
      at the University Teaching Hospital (UTH), the site of the only pediatric
      oncology ward in Zambia. METHODS: Using an established database, a retrospective
      cohort study was conducted of children aged 0-15 years admitted to the pediatric
      oncology ward between July 2008 and June 2010 with suspected cancer. Diagnosis,
      mode of diagnosis, treatment outcome, and risk factors for abandonment of
      treatment were abstracted from this database and clinical medical records.
      RESULTS: Among 162 children treated at the UTH during the study time period that
      met inclusion criteria, only 8.0% completed a treatment regimen with most of the
      patients dying during treatment or abandoning care. In multivariable analysis,
      shorter distance from home to the UTH was associated with a lower risk of
      treatment abandonment (Adjusted Odds Ratio [aOR]  = 0.48 (95% confidence interval
      [CI] 0.23-0.97). Conversely maternal education less than secondary school was
      associated with increased risk for abandonment (aOR = 1.65; 95% CI 1.05-2.58).
      CONCLUSIONS: Despite availability of dedicated pediatric oncology treatment,
      treatment completion rates are poor, due in part to the logistical challenges
      faced by families, low educational status, and significant distance from the
      hospital. Alternative treatment delivery strategies are required to bring
      effective pediatric oncology care to the patients in need, as their ability to
      come to and remain at a central tertiary care facility for treatment is limited.
      We suggest that the extensive system now in place in most of sub-Saharan Africa
      that sustains life-long antiretroviral therapy for children with human
      immunodeficiency virus (HIV) infection be adapted for pediatric cancer treatment
      to improve outcome.

PMID- 24586528
TI  - Functional polymorphisms in interleukin-23 receptor and susceptibility to
      esophageal squamous cell carcinoma in Chinese population.
AB  - BACKGROUND: As a key element in the T-helper 17 (Th17) cell-mediated inflammatory
      process, interleukin-23 receptor (IL-23R) plays a crucial role in the
      pathogenesis of cancer. Single nucleotide polymorphisms (SNPs) in IL-23R have
      been frequently studied in several previous case-control cancer studies, but its
      association with esophageal squamous cell carcinoma (ESCC) in Chinese population
      has not been investigated. This study examined whether genetic polymorphisms in
      IL-23R were associated with ESCC susceptibility. METHODS: A hospital-based case
      control study of 684 ESCC patients and 1064 healthy controls was performed to
      assess the association between four previous reported IL-23R genotypes
      (rs6682925, rs6683039, rs1884444 and rs10889677) and ESCC risk. The results
      revealed that the C allele of the rs10889677A>C polymorphism in the 3'UTR of IL
      23R gene was inversely associated with the risk of ESCC. RESULTS: The
      rs10889677AC genotype had significantly decreased cancer risk (odds ratio [OR]  =
      0.85, 95% confidence interval [CI]  = 0.69-1.01) compared to subjects homozygous
      carriers of rs10889677AA, the risk decreased even further in those carrying
      rs10889677CC genotype (OR = 0.64, 95% CI = 0.44-0.93). No significant association
      was found between the other three polymorphisms and the risk of ESCC. CONCLUSION:
      These findings indicated that rs10889677A>C polymorphism in IL-23R may play a
      protective role in mediating the risk of ESCC.

PMID- 24586530
TI  - Bone morphogenetic protein signaling protects against cerulein-induced pancreatic
      fibrosis.
AB  - Bone morphogenetic proteins (BMPs) have an anti-fibrogenic function in the
      kidney, lung, and liver. However, their role in chronic pancreatitis (CP) is
      unknown. The aim of this study was to define the anti-fibrogenic role of BMP
      signaling in the pancreas in vivo under CP induction. Mice with a deletion of BMP
      type II receptor (BMPR2(+/-)) were used in this study in comparison with wild
      type mice. CP was induced by repetitive cerulein injection intraperitoneally for
      4 weeks, and the severity of CP was evaluated. Pancreatic stellate cells (PSCs)
      were isolated from the mice and treated with BMP2 and TGF-beta in vitro, and
      extracellular matrix protein (ECM) production was measured. Smad and mitogen
      activated protein kinase (MAPK) signaling was also evaluated. BMPR2(+/-) mice
      revealed a greater pancreatic fibrosis, PSC activation and leukocyte infiltration
      after CP induction compared to wild-type mice (P<0.05). Under CP induction,
      phospho (p)Smad1/5/8 was elevated in wild-type mice and this effect was abolished
      in BMPR2(+/-) mice; pSmad2 and pp38(MAPK) were further enhanced in BMPR2(+/-)
      mice compared to wild-type mice (P<0.05). In vitro, BMP2 inhibited TGF-beta
      induced ECM protein fibronectin production in wild-type PSCs; this effect was
      abolished in BMPR2(+/-) PSCs (P<0.05). In BMPR2(+/-) PSCs, pSmad1/5/8 level was
      barely detectable upon BMP2 stimulation, while pSmad2 level was further enhanced
      by TGF-beta stimulation, compared to wild-type PSCs (P<0.05). BMPR2/Smad1/5/8
      signaling plays a protective role against cerulein-induced pancreatic fibrosis by
      inhibiting Smad2 and p38(MAPK) signaling pathways. 

PMID- 24586529
TI  - A compartmentalized mathematical model of the beta1-adrenergic signaling system
      in mouse ventricular myocytes.
AB  - The beta1-adrenergic signaling system plays an important role in the functioning
      of cardiac cells. Experimental data shows that the activation of this system
      produces inotropy, lusitropy, and chronotropy in the heart, such as increased
      magnitude and relaxation rates of [Ca(2+)]i transients and contraction force, and
      increased heart rhythm. However, excessive stimulation of beta1-adrenergic
      receptors leads to heart dysfunction and heart failure. In this paper, a
      comprehensive, experimentally based mathematical model of the beta1-adrenergic
      signaling system for mouse ventricular myocytes is developed, which includes
      major subcellular functional compartments (caveolae, extracaveolae, and cytosol).
      The model describes biochemical reactions that occur during stimulation of beta1
      adrenoceptors, changes in ionic currents, and modifications of Ca(2+) handling
      system. Simulations describe the dynamics of major signaling molecules, such as
      cyclic AMP and protein kinase A, in different subcellular compartments; the
      effects of inhibition of phosphodiesterases on cAMP production; kinetics and
      magnitudes of phosphorylation of ion channels, transporters, and Ca(2+) handling
      proteins; modifications of action potential shape and duration; magnitudes and
      relaxation rates of [Ca(2+)]i transients; changes in intracellular and
      transmembrane Ca(2+) fluxes; and [Na(+)]i fluxes and dynamics. The model
      elucidates complex interactions of ionic currents upon activation of beta1
      adrenoceptors at different stimulation frequencies, which ultimately lead to a
      relatively modest increase in action potential duration and significant increase
      in [Ca(2+)]i transients. In particular, the model includes two subpopulations of
      the L-type Ca(2+) channels, in caveolae and extracaveolae compartments, and their
      effects on the action potential and [Ca(2+)]i transients are investigated. The
      presented model can be used by researchers for the interpretation of experimental
      data and for the developments of mathematical models for other species or for
      pathological conditions. 

PMID- 24586531
TI  - Differential function of Themis CABIT domains during T cell development.
AB  - Themis (also named Gasp) is a newly identified Grb2-binding protein that is
      essential for thymocyte positive selection. Despite the possible involvement of
      Themis in TCR-mediated signal transduction, its function remains unresolved and
      controversial. Themis contains two functionally uncharacterized regions called
      CABIT (cysteine-containing, all-beta in Themis) domains, a nuclear localization
      signal (NLS), and a proline-rich sequence (PRS). To elucidate the role of these
      motifs in Themis's function in vivo, we established a series of mutant Themis
      transgenic mice on a Themis(-/-) background. Deletion of the highly conserved
      Core motif of CABIT1 or CABIT2 (Core1 or Core2, respectively), the NLS, or the
      PRS abolished Grb2-association, as well as TCR-dependent tyrosine-phosphorylation
      and the ability to induce positive selection in the thymus. The NLS and Core1
      motifs were required for the nuclear localization of Themis, whereas Core2 and
      PRS were not. Furthermore, expression of DeltaCore1- but not DeltaCore2-Themis
      conferred dominant negative-type inhibition on T cell development. Collectively,
      our current results indicate that PRS, NLS, CABIT1, and CABIT2 are all required
      for positive selection, and that each of the CABIT domains exerts distinct
      functions during positive selection. 

PMID- 24586532
TI  - Structural analysis of viral infectivity factor of HIV type 1 and its interaction
      with A3G, EloC and EloB.
AB  - BACKGROUND: The virion infectivity factor (Vif) is an accessory protein, which is
      essential for HIV replication in host cells. Vif neutralizes the antiviral host
      protein APOBEC3 through recruitment of the E3 ubiquitin ligase complex.
      METHODOLOGY: Fifty thousand Vif models were generated using the ab initio relax
      protocol of the Rosetta algorithm from sets of three- and nine-residue fragments
      using the fragment Monte Carlo insertion-simulated annealing strategy, which
      favors protein-like features, followed by an all-atom refinement. In the
      protocol, a constraints archive was used to define the spatial relationship
      between the side chains from Cys/His residues and zinc ions that formed the zinc
      finger motif that is essential for Vif function. We also performed centroids
      analysis and structural analysis with respect to the formation of the zinc
      finger, and the residue disposal in the protein binding domains. Additionally,
      molecular docking was used to explore details of Vif-A3G and Vif-EloBC
      interactions. Furthermore, molecular dynamics simulation was used to evaluate the
      stability of the complexes Vif-EloBC-A3G and Vif-EloC. PRINCIPAL FINDINGS: The
      zinc in the HCCH domain significantly alters the folding of Vif and changes the
      structural dynamics of the HCCH region. Ab initio modeling indicated that the Vif
      zinc-finger possibly displays tetrahedral geometry as suggested by Mehle et al.
      (2006). Our model also showed that the residues L146 and L149 of the BC-box motif
      bind to EloC by hydrophobic interactions, and the residue P162 of the PPLP motif
      is important to EloB binding. CONCLUSIONS/SIGNIFICANCE: The model presented here
      is the first complete three-dimensional structure of the Vif. The interaction of
      Vif with the A3G protein and the EloBC complex is in agreement with empirical
      data that is currently available in the literature and could therefore provide
      valuable structural information for advances in rational drug design.

PMID- 24586533
TI  - Topoisomerase inhibitors modulate gene expression of B-cell translocation gene 2
      and prostate specific antigen in prostate carcinoma cells.
AB  - Camptothecin (CPT) and doxorubicin (DOX) have been demonstrated to have potent
      anti-tumor activity. The B-cell translocation gene 2 (BTG2) is involved in the
      regulation of cell cycle progression. We evaluated the molecular mechanisms of
      CPT and DOX on cell proliferation and the expressions of BTG2 and prostate
      specific antigen (PSA) in prostate carcinoma cells. Our results indicated that
      CPT or DOX treatments induced Go/G1 cell cycle arrest in LNCaP cells and
      apoptosis at higher dosage. Immunoblot and transient gene expression assay
      indicated that CPT or DOX treatments induced p53 and BTG2 gene expression, with
      the later effect dependent on the p53 response element within BTG2 promoter area
      since mutation of the p53 response element from GGGAAAGTCC to GGAGTCC or from
      GGCAGAGCCC to GGCACC by site-directed mutagenesis abolished the stimulation of
      CPT or DOX on the BTG2 promoter activity, which is also supported by our results
      that cotreatments of pifithrin-alpha, an inhibitor of p53 dependent
      transcriptional activation, blocked the induction of CPT or DOX on BTG2 gene
      expression. CPT or DOX also downregulated the protein expressions of androgen
      receptor (AR) and PSA. Transient gene expression assays suggested that CPT or
      DOX's attenuation of PSA promoter activity is dependent on both the androgen and
      p53 response elements within of the PSA promoter. Our results indicated that CPT
      and DOX attenuate cell proliferation via upregulation of BTG2 gene expression
      through the p53-dependent pathway. The CPT and DOX block the PSA gene expression
      by upregulation of p53 activity and downregulation of androgen receptor activity.

PMID- 24586534
TI  - Women's experiences with oral and vaginal pre-exposure prophylaxis: the VOICE-C
      qualitative study in Johannesburg, South Africa.
AB  - BACKGROUND: In VOICE, a multisite HIV pre-exposure prophylaxis (PrEP) trial,
      plasma drug levels pointed to widespread product nonuse, despite high adherence
      estimated by self-reports and clinic product counts. Using a socio-ecological
      framework (SEF), we explored socio-cultural and contextual factors that
      influenced participants' experience of daily vaginal gel and oral tablet regimens
      in VOICE. METHODS: In Johannesburg, a qualitative ancillary study was
      concurrently conducted among randomly selected VOICE participants assigned to in
      depth interviews (n = 41), serial ethnographic interviews (n = 21), or focus
      group discussions (n = 40). Audiotaped interviews were transcribed, translated,
      and coded thematically for analysis. RESULTS: Of the 102 participants, the mean
      age was 27 years, and 96% had a primary sex partner with whom 43% cohabitated.
      Few women reported lasting nonuse, which they typically attributed to missed
      visits, lack of product replenishments, and family-related travel or work. Women
      acknowledged occasionally skipping or mistiming doses because they forgot, were
      busy, felt lazy or bored, feared or experienced side effects. However, nearly all
      knew or heard of other study participants who did not use products daily. Three
      overarching themes emerged from further analyses: ambivalence toward research,
      preserving a healthy status, and managing social relationships. These themes
      highlighted the profound and complex meanings associated with participating in a
      blinded HIV PrEP trial and taking antiretroviral-based products. The unknown
      efficacy of products, their connection with HIV infection, challenges with daily
      regimen given social risks, lack of support-from partners and significant others
      and the relationship tradeoffs entailed by using the products appear to
      discourage adequate product use. CONCLUSIONS: Personal acknowledgment of product
      nonuse was challenging. This qualitative inquiry highlighted key influences at
      all SEF levels that shaped women's perceptions of trial participation and
      experiences with investigational products. Whether these impacted women's
      behaviors and may have contributed to ineffective trial results warrants further
      investigation.

PMID- 24586535
TI  - Reducing insecticide use in broad-acre grains production: an Australian study.
AB  - Prophylactic use of broad-spectrum insecticides is a common feature of broad-acre
      grains production systems around the world. Efforts to reduce pesticide use in
      these systems have the potential to deliver environmental benefits to large areas
      of agricultural land. However, research and extension initiatives aimed at
      decoupling pest management decisions from the simple act of applying a cheap
      insecticide have languished. This places farmers in a vulnerable position of high
      reliance on a few products that may lose their efficacy due to pests developing
      resistance, or be lost from use due to regulatory changes. The first step towards
      developing Integrated Pest Management (IPM) strategies involves an increased
      efficiency of pesticide inputs. Especially challenging is an understanding of
      when and where an insecticide application can be withheld without risking yield
      loss. Here, we quantify the effect of different pest management strategies on the
      abundance of pest and beneficial arthropods, crop damage and yield, across five
      sites that span the diversity of contexts in which grains crops are grown in
      southern Australia. Our results show that while greater insecticide use did
      reduce the abundance of many pests, this was not coupled with higher yields.
      Feeding damage by arthropod pests was seen in plots with lower insecticide use
      but this did not translate into yield losses. For canola, we found that plots
      that used insecticide seed treatments were most likely to deliver a yield
      benefit; however other insecticides appear to be unnecessary and economically
      costly. When considering wheat, none of the insecticide inputs provided an
      economically justifiable yield gain. These results indicate that there are
      opportunities for Australian grain growers to reduce insecticide inputs without
      risking yield loss in some seasons. We see this as the critical first step
      towards developing IPM practices that will be widely adopted across intensive
      production systems. 

PMID- 24586536
TI  - Population structure of Staphylococcus aureus from Trinidad & Tobago.
AB  - It has been shown previously that high rates of methicillin- and mupirocin
      resistant Staphylococcus aureus exist in the Caribbean islands of Trinidad and
      Tobago, as well as a high prevalence of Panton-Valentine leukocidin-positive S.
      aureus. Beyond these studies, limited typing data have been published. In order
      to obtain insight into the population structure not only of MRSA but also of
      methicillin-susceptible S. aureus, 294 clinical isolates collected in 2012/2013
      were typed by microarray hybridisation. A total of 15.31% of the tested isolates
      were MRSA and 50.00% were PVL-positive. The most common MSSA strains were PVL
      positive CC8-MSSA (20.41% of all isolates tested), PVL-positive CC152-MSSA
      (9.52%) and PVL-positive CC30-MSSA (8.84%) while the most common MRSA were ST239
      MRSA-III&SCCmer (9.18%) and ST8-MRSA-IV, "USA300" (5.78%). 2.38% of characterised
      isolates belonged to distinct strains likely to be related to "Staphylococcus
      argenteus" lineages. The population structure of S. aureus isolates suggests an
      importation of strains from Africa, endemicity of PVL-positive MSSA (mainly CC8)
      and of ST239-MRSA-III, and a recent emergence of the PVL-positive CC8-MRSA-IV
      strain "USA300". 

PMID- 24586537
TI  - Extracellular vesicles modulate host-microbe responses by altering TLR2 activity
      and phagocytosis.
AB  - Oral delivery of Gram positive bacteria, often derived from the genera
      Lactobacillus or Bifidobacterium, can modulate immune function. Although the
      exact mechanisms remain unclear, immunomodulatory effects may be elicited through
      the direct interaction of these bacteria with the intestinal epithelium or
      resident dendritic cell (DC) populations. We analyzed the immune activation
      properties of Lactobacilli and Bifidobacterium species and made the surprising
      observation that cellular responses in vitro were differentially influenced by
      the presence of serum, specifically the extracellular vesicle (EV) fraction. In
      contrast to the tested Lactobacilli species, tested Bifidobacterium species
      induce TLR2/6 activity which is inhibited by the presence of EVs. Using specific
      TLR ligands, EVs were found to enhance cellular TLR2/1 and TLR4 responses while
      TLR2/6 responses were suppressed. No effect could be observed on cellular TLR5
      responses. We determined that EVs play a role in bacterial aggregation,
      suggesting that EVs interact with bacterial surfaces. EVs were found to slightly
      enhance DC phagocytosis of Bifidobacterium breve whereas phagocytosis of
      Lactobacillus rhamnosus was virtually absent upon serum EV depletion. DC uptake
      of a non-microbial substance (dextran) was not affected by the different serum
      fractions suggesting that EVs do not interfere with DC phagocytic capacity but
      rather modify the DC-microbe interaction. Depending on the microbe, combined
      effects of EVs on TLR activity and phagocytosis result in a differential
      proinflammatory DC cytokine release. Overall, these data suggest that EVs play a
      yet unrecognized role in host-microbe responses, not by interfering in recipient
      cellular responses but via attachment to, or scavenging of, microbe-associated
      molecular patterns. EVs can be found in any tissue or bodily fluid, therefore
      insights into EV-microbe interactions are important in understanding the
      mechanism of action of potential probiotics and gut immune homeostasis.

PMID- 24586538
TI  - A vanillin derivative causes mitochondrial dysfunction and triggers oxidative
      stress in Cryptococcus neoformans.
AB  - Vanillin is a well-known food and cosmetic additive and has antioxidant and
      antimutagenic properties. It has also been suggested to have antifungal activity
      against major human pathogenic fungi, although it is not very effective. In this
      study, the antifungal activities of vanillin and 33 vanillin derivatives against
      the human fungal pathogen Cryptococcus neoformans, the main pathogen of
      cryptococcal meningitis in immunocompromised patients, were investigated. We
      found a structural correlation between the vanillin derivatives and antifungal
      activity, showing that the hydroxyl or alkoxy group is more advantageous than the
      halogenated or nitrated group in benzaldehyde. Among the vanillin derivatives
      with a hydroxyl or alkoxy group, o-vanillin and o-ethyl vanillin showed the
      highest antifungal activity against C. neoformans. o-Vanillin was further studied
      to understand the mechanism of antifungal action. We compared the transcriptome
      of C. neoformans cells untreated or treated with o-vanillin by using RNA
      sequencing and found that the compound caused mitochondrial dysfunction and
      triggered oxidative stress. These antifungal mechanisms of o-vanillin were
      experimentally confirmed by the significantly reduced growth of the mutants
      lacking the genes involved in mitochondrial functions and oxidative stress
      response. 

PMID- 24586539
TI  - O-hexadecyl-dextran entrapped berberine nanoparticles abrogate high glucose
      stress induced apoptosis in primary rat hepatocytes.
AB  - Nanotized phytochemicals are being explored by researchers for promoting their
      uptake and effectiveness at lower concentrations. In this study, O-hexadecyl
      dextran entrapped berberine chloride nanoparticles (BC-HDD NPs) were prepared,
      and evaluated for their cytoprotective efficacy in high glucose stressed primary
      hepatocytes and the results obtained compared with bulk berberine chloride (BBR)
      treatment. The nanotized formulation treated primary hepatocytes that were
      exposed to high glucose (40 mM), showed increased viability compared to the bulk
      BBR treated cells. BC-HDD NPs reduced the ROS generation by ~ 3.5 fold during co
      treatment, prevented GSH depletion by ~ 1.6 fold, reduced NO formation by ~ 5
      fold and significantly prevented decline in SOD activity in stressed cells. Lipid
      peroxidation was also prevented by ~ 1.9 fold in the presence of these NPs
      confirming the antioxidant capacity of the formulation. High glucose stress
      increased Bax/Bcl2 ratio followed by mitochondrial depolarization and activation
      of caspase-9/-3 confirming involvement of mitochondrial pathway of apoptosis in
      the exposed cells. Co- and post-treatment of BC-HDD NPs prevented depolarization
      of mitochondrial membrane, reduced Bax/Bcl2 ratio and prevented externalization
      of phosphatidyl-serine confirming their anti-apoptotic capacity in those cells.
      Sub-G1 phase apparent in high glucose stressed cells was not seen in BC-HDD NPs
      treated cells. The present study reveals that BC-HDD NPs at ~ 20 fold lower
      concentration are as effective as BBR in preventing high glucose induced
      oxidative stress, mitochondrial depolarization and downstream events of apoptotic
      cell death.

PMID- 24586540
TI  - Motion of the esophagus due to cardiac motion.
AB  - When imaging studies (e.g. CT) are used to quantify morphological changes in an
      anatomical structure, it is necessary to understand the extent and source of
      motion which can give imaging artifacts (e.g. blurring or local distortion). The
      objective of this study was to assess the magnitude of esophageal motion due to
      cardiac motion. We used retrospective electrocardiogram-gated contrast-enhanced
      computed tomography angiography images for this study. The anatomic region from
      the carina to the bottom of the heart was taken at deep-inspiration breath hold
      with the patients' arms raised above their shoulders, in a position similar to
      that used for radiation therapy. The esophagus was delineated on the diastolic
      phase of cardiac motion, and deformable registration was used to sequentially
      deform the images in nearest-neighbor phases among the 10 cardiac phases,
      starting from the diastolic phase. Using the 10 deformation fields generated from
      the deformable registration, the magnitude of the extreme displacements was then
      calculated for each voxel, and the mean and maximum displacement was calculated
      for each computed tomography slice for each patient. The average maximum
      esophageal displacement due to cardiac motion for all patients was 5.8 mm
      (standard deviation: 1.6 mm, maximum: 10.0 mm) in the transverse direction. For
      21 of 26 patients, the largest esophageal motion was found in the inferior region
      of the heart; for the other patients, esophageal motion was approximately
      independent of superior-inferior position. The esophagus motion was larger at
      cardiac phases where the electrocardiogram R-wave occurs. In conclusion, the
      magnitude of esophageal motion near the heart due to cardiac motion is similar to
      that due to other sources of motion, including respiratory motion and intra
      fraction motion. A larger cardiac motion will result into larger esophagus motion
      in a cardiac cycle. 

PMID- 24586541
TI  - Impaired angiogenesis during fracture healing in GPCR kinase 2 interacting
      protein-1 (GIT1) knock out mice.
AB  - G protein coupled receptor kinase 2 (GRK2) interacting protein-1 (GIT1), is a
      scaffold protein that plays an important role in angiogenesis and osteoclast
      activity. We have previously demonstrated that GIT1 knockout (GIT1 KO) mice have
      impaired angiogenesis and dysregulated osteoclast podosome formation leading to a
      reduction in the bone resorbing ability of these cells. Since both angiogenesis
      and osteoclast-mediated bone remodeling are involved in the fracture healing
      process, we hypothesized that GIT1 participates in the normal progression of
      repair following bone injury. In the present study, comparison of fracture
      healing in wild type (WT) and GIT1 KO mice revealed altered healing in mice with
      loss of GIT1 function. Alcian blue staining of fracture callus indicated a
      persistence of cartilagenous matrix in day 21 callus samples from GIT1 KO mice
      which was temporally correlated with increased type 2 collagen immunostaining.
      GIT1 KO mice also showed a decrease in chondrocyte proliferation and apoptosis at
      days 7 and 14, as determined by PCNA and TUNEL staining. Vascular microcomputed
      tomography analysis of callus samples at days 7, 14 and 21 revealed decreased
      blood vessel volume, number, and connection density in GIT1 KO mice compared to
      WT controls. Correlating with this, VEGF-A, phospho-VEGFR2 and PECAM1 (CD31) were
      decreased in GIT1 KO mice, indicating reduced angiogenesis with loss of GIT1.
      Finally, calluses from GIT1 KO mice displayed a reduced number of tartrate
      resistant acid phosphatase-positive osteoclasts at days 14 and 21. Collectively,
      these results indicate that GIT1 is an important signaling participant in
      fracture healing, with gene ablation leading to reduced callus vascularity and
      reduced osteoclast number in the healing callus. 

PMID- 24586542
TI  - Male-specific association between dopamine receptor D4 gene methylation and
      schizophrenia.
AB  - OBJECTIVE: The goal of our study was to investigate whether DRD4 gene DNA
      methylation played an important role in the susceptibility of Han Chinese SCZ.
      METHODS: Using the bisulphite pyrosequencing technology, DNA methylation levels
      of 6 CpG dinucleotides in DRD4 CpG island were measured among 30 paranoid SCZ
      patients, 30 undifferentiated SCZ patients, and 30 age- and gender-matched
      healthy controls. RESULTS: Strong correlation was observed among the six CpG
      sites (r>0.5, P<0.01), thus average methylation levels were applied thereafter.
      Our results indicated that there was a significant association between DRD4
      methylation and the risk of SCZ (P = 0.003), although there was no significant
      difference in DRD4 methylation between the two SCZ subtypes (P = 0.670). A
      breakdown analysis by gender showed that the significant association of DRD4
      methylation and SCZ was driven by males (P<0.001) but not by females (P = 0.835).
      DRD4 methylation was significantly associated with p300 in male SCZ patients (r =
      -0.543, P = 0.005) but not in female SCZ patients (r = 0.110, P = 0.599).
      Moreover, receiver operating characteristic (ROC) curves showed DRD4 methylation
      was able to predict the status of SCZ in males [area under curve (AUC) = 0.832, P
      = 0.002] but not in females (AUC = 0.483, P = 0.876). Finally, a further
      expression experiment showed that DRD4 methylation in the gene body was
      positively associated with gene expression, although the exact mechanism of gene
      regulation remained unknown for this interesting DRD4 methylation. CONCLUSION:
      The gender disparity in the DRD4 DNA methylation provides novel insights into the
      pathogenesis of SCZ.

PMID- 24586544
TI  - High-level recombinant human lysozyme expressed in milk of transgenic pigs can
      inhibit the growth of Escherichia coli in the duodenum and influence intestinal
      morphology of sucking pigs.
AB  - Lysozyme is often used as a feed additive and acts as an antimicrobial protein
      that enhances immune function and defends against pathogenic bacteria in pigs. In
      this study, we genetically added recombinant human lysozyme (rhLZ) to sow milk by
      somatic cell nuclear transfer and investigated whether the presence of
      recombinant human lysozyme can influence intestinal microbiota and morphology in
      sucking pigs. We generated transgenic cloned pigs and the first-generation
      hybrids (F1) produced high levels of rhLZ in milk. The average concentration of
      rhLZ was 116.34 +/- 24.46 mg/L in the milk of F1 sows, which was 1500-fold higher
      than that of the native pig lysozyme. In vitro, it was demonstrated that rhLZ in
      milk of transgenic pigs had enzyme levels at 92,272 +/- 26,413 U/mL. In a feeding
      experiment, a total of 40 newborn piglets were nursed by four transgenic sows and
      four sibling non-transgenic sows (F1), with five piglets per gilt. The piglets
      were allowed to nurse for 21 days and the sow milk was the only source of
      nutrition for the piglets. All piglets were slaughtered on postnatal day 22. Six
      types of bacteria were cultured and analyzed to detect the impact of rhLZ on gut
      microbiota. The number of Escherichia coli in the duodenum of piglets reared by
      transgenic sows was significantly decreased (p<0.001) and their villus height to
      crypt depth ratio in the intestine were increased due to the significant decrease
      of crypt depth in the duodenum, jejunum, and ileum (p<0.001). Together, we
      successfully generated rhLZ transgenic cloned pigs and elevated lysozyme level in
      nuring piglets. The results of the feeding experiments demonstrated that rhLZ
      enhanced milk can inhibit the growth of E. coli in the duodenum and positively
      influence intestinal morphology without adversely affecting weight gain or piglet
      growth.

PMID- 24586545
TI  - A mixed modeling approach to predict the effect of environmental modification on
      species distributions.
AB  - Human infrastructures can modify ecosystems, thereby affecting the occurrence and
      spatial distribution of organisms, as well as ecosystem functionality.
      Sustainable development requires the ability to predict responses of species to
      anthropogenic pressures. We investigated the large scale, long term effect of
      important human alterations of benthic habitats with an integrated approach
      combining engineering and ecological modelling. We focused our analysis on the
      Oosterschelde basin (The Netherlands), which was partially embanked by a storm
      surge barrier (Oosterscheldekering, 1986). We made use of 1) a prognostic
      (numerical) environmental (hydrodynamic) model and 2) a novel application of
      quantile regression to Species Distribution Modeling (SDM) to simulate both the
      realized and potential (habitat suitability) abundance of four macrozoobenthic
      species: Scoloplos armiger, Peringia ulvae, Cerastoderma edule and Lanice
      conchilega. The analysis shows that part of the fluctuations in macrozoobenthic
      biomass stocks during the last decades is related to the effect of the coastal
      defense infrastructures on the basin morphology and hydrodynamics. The
      methodological framework we propose is particularly suitable for the analysis of
      large abundance datasets combined with high-resolution environmental data. Our
      analysis provides useful information on future changes in ecosystem functionality
      induced by human activities. 

PMID- 24586543
TI  - Abnormal striatal BOLD responses to reward anticipation and reward delivery in
      ADHD.
AB  - Altered reward processing has been proposed to contribute to the symptoms of
      attention deficit hyperactivity disorder (ADHD). The neurobiological mechanism
      underlying this alteration remains unclear. We hypothesize that the transfer of
      dopamine release from reward to reward-predicting cues, as normally observed in
      animal studies, may be deficient in ADHD. Functional magnetic resonance imaging
      (fMRI) was used to investigate striatal responses to reward-predicting cues and
      reward delivery in a classical conditioning paradigm. Data from 14 high
      functioning and stimulant-naive young adults with elevated lifetime symptoms of
      ADHD (8 males, 6 females) and 15 well-matched controls (8 males, 7 females) were
      included in the analyses. During reward anticipation, increased blood-oxygen
      level-dependent (BOLD) responses in the right ventral and left dorsal striatum
      were observed in controls, but not in the ADHD group. The opposite pattern was
      observed in response to reward delivery; the ADHD group demonstrated
      significantly greater BOLD responses in the ventral striatum bilaterally and the
      left dorsal striatum relative to controls. In the ADHD group, the number of
      current hyperactivity/impulsivity symptoms was inversely related to ventral
      striatal responses during reward anticipation and positively associated with
      responses to reward. The BOLD response patterns observed in the striatum are
      consistent with impaired predictive dopamine signaling in ADHD, which may explain
      altered reward-contingent behaviors and symptoms of ADHD. 

PMID- 24586546
TI  - Postsynaptic odorant concentration dependent inhibition controls temporal
      properties of spike responses of projection neurons in the moth antennal lobe.
AB  - Although odorant concentration-response characteristics of olfactory neurons have
      been widely investigated in a variety of animal species, the effect of odorant
      concentration on neural processing at circuit level is still poorly understood.
      Using calcium imaging in the silkmoth (Bombyx mori) pheromone processing circuit
      of the antennal lobe (AL), we studied the effect of odorant concentration on
      second-order projection neuron (PN) responses. While PN calcium responses of
      dendrites showed monotonic increases with odorant concentration, calcium
      responses of somata showed decreased responses at higher odorant concentrations
      due to postsynaptic inhibition. Simultaneous calcium imaging and
      electrophysiology revealed that calcium responses of PN somata but not dendrites
      reflect spiking activity. Inhibition shortened spike response duration rather
      than decreasing peak instantaneous spike frequency (ISF). Local interneurons
      (LNs) that were specifically activated at high odorant concentrations at which PN
      responses were suppressed are the putative source of inhibition. Our results
      imply the existence of an intraglomerular mechanism that preserves time
      resolution in olfactory processing over a wide odorant concentration range. 

PMID- 24586547
TI  - Imbalanced expression of Vcan mRNA splice form proteins alters heart morphology
      and cellular protein profiles.
AB  - The fundamental importance of the proteoglycan versican to early heart formation
      was clearly demonstrated by the Vcan null mouse called heart defect (hdf). Total
      absence of the Vcan gene halts heart development at a stage prior to the heart's
      pulmonary/aortic outlet segment growth. This creates a problem for determining
      the significance of versican's expression in the forming valve precursors and
      vascular wall of the pulmonary and aortic roots. This study presents data from a
      mouse model, Vcan ((tm1Zim)), of heart defects that results from deletion of exon
      7 in the Vcan gene. Loss of exon 7 prevents expression of two of the four
      alternative splice forms of the Vcan gene. Mice homozygous for the exon 7
      deletion survive into adulthood, however, the inability to express the V2 or V0
      forms of versican results in ventricular septal defects, smaller cushions/valve
      leaflets with diminished myocardialization and altered pulmonary and aortic
      outflow tracts. We correlate these phenotypic findings with a large-scale
      differential protein expression profiling to identify compensatory alterations in
      cardiac protein expression at E13.5 post coitus that result from the absence of
      Vcan exon 7. The Vcan ((tm1Zim)) hearts show significant changes in the relative
      abundance of several cytoskeletal and muscle contraction proteins including some
      previously associated with heart disease. These alterations define a protein
      fingerprint that provides insight to the observed deficiencies in pre
      valvular/septal cushion mesenchyme and the stability of the myocardial phenotype
      required for alignment of the outflow tract with the heart ventricles. 

PMID- 24586548
TI  - Twisted gastrulation, a BMP antagonist, exacerbates podocyte injury.
AB  - Podocyte injury is the first step in the progression of glomerulosclerosis.
      Previous studies have demonstrated the beneficial effect of bone morphogenetic
      protein 7 (Bmp7) in podocyte injury and the existence of native Bmp signaling in
      podocytes. Local activity of Bmp7 is controlled by cell-type specific Bmp
      antagonists, which inhibit the binding of Bmp7 to its receptors. Here we show
      that the product of Twisted gastrulation (Twsg1), a Bmp antagonist, is the
      central negative regulator of Bmp function in podocytes and that Twsg1 null mice
      are resistant to podocyte injury. Twsg1 was the most abundant Bmp antagonist in
      murine cultured podocytes. The administration of Bmp induced podocyte
      differentiation through Smad signaling, whereas the simultaneous administration
      of Twsg1 antagonized the effect. The administration of Bmp also inhibited
      podocyte proliferation, whereas simultaneous administration of Twsg1 antagonized
      the effect. Twsg1 was expressed in the glomerular parietal cells (PECs) and
      distal nephron of the healthy kidney, and additionally in damaged glomerular
      cells in a murine model of podocyte injury. Twsg1 null mice exhibited milder
      hypoalbuminemia and hyperlipidemia, and milder histological changes while
      maintaining the expression of podocyte markers during podocyte injury model.
      Taken together, our results show that Twsg1 plays a critical role in the
      modulation of protective action of Bmp7 on podocytes, and that inhibition of
      Twsg1 is a promising means of development of novel treatment for podocyte injury.

PMID- 24586549
TI  - Rac1 participates in thermally induced alterations of the cytoskeleton, cell
      morphology and lipid rafts, and regulates the expression of heat shock proteins
      in B16F10 melanoma cells.
AB  - Eukaryotic cells exhibit a characteristic response to hyperthermic treatment,
      involving morphological and cytoskeletal alterations and the induction of heat
      shock protein synthesis. Small GTPases of the Ras superfamily are known to serve
      as molecular switches which mediate responses to extracellular stimuli. We
      addressed here how small GTPase Rac1 integrates signals from heat stress and
      simultaneously induces various cellular changes in mammalian cells. As evidence
      that Rac1 is implicated in the heat shock response, we first demonstrated that
      both mild (41.5 degrees C) and severe (43 degrees C) heat shock induced membrane
      translocation of Rac1. Following inhibition of the activation or palmitoylation
      of Rac1, the size of its plasma membrane-bound pool was significantly decreased
      while the heat shock-induced alterations in the cytoskeleton and cell morphology
      were prevented. We earlier documented that the size distribution pattern of
      cholesterol-rich rafts is temperature dependent and hypothesized that this is
      coupled to the triggering mechanism of stress sensing and signaling.
      Interestingly, when plasma membrane localization of Rac1 was inhibited, a
      different and temperature independent average domain size was detected. In
      addition, inhibition of the activation or palmitoylation of Rac1 resulted in a
      strongly decreased expression of the genes of major heat shock proteins hsp25 and
      hsp70 under both mild and severe heat stress conditions. 

PMID- 24586550
TI  - A proteomic study on molecular mechanism of poor grain-filling of rice (Oryza
      sativa L.) inferior spikelets.
AB  - Cultivars of rice (Oryza sativa L.), especially of the type with large spikelets,
      often fail to reach the yield potential as expected due to the poor grain-filling
      on the later flowering inferior spikelets (in contrast to the earlier-flowering
      superior spikelets). The present study showed that the size and grain weight of
      superior spikelets (SS) was greater than those of inferior spikelets (IS), and
      the carbohydrate supply should not be the major problem for the poor grain
      filling because there was adequate amount of sucrose in IS at the initial grain
      filling stage. High resolution two-dimensional gel electrophoresis (2-DE) in
      combination with Coomassie-brilliant blue (CBB) and Pro-Q Diamond phosphoprotein
      fluorescence stain revealed that 123 proteins in abundance and 43 phosphoproteins
      generated from phosphorylation were significantly different between SS and IS.
      These proteins and phosphoproteins were involved in different cellular and
      metabolic processes with a prominently functional skew toward metabolism and
      protein synthesis/destination. Expression analyses of the proteins and
      phosphoproteins associated with different functional categories/subcategories
      indicated that the starch synthesis, central carbon metabolism, N metabolism and
      cell growth/division were closely related to the poor grain-filling of IS.
      Functional and expression pattern studies also suggested that 14-3-3 proteins
      played important roles in IS poor grain-filling by regulating the activity of
      starch synthesis enzymes. The proteome and phosphoproteome obtained from this
      study provided a better understanding of the molecular mechanism of the IS poor
      grain-filling. They were also expected to be highly useful for improving the
      grain filling of rice. 

PMID- 24586551
TI  - A system to automatically classify and name any individual genome-sequenced
      organism independently of current biological classification and nomenclature.
AB  - A broadly accepted and stable biological classification system is a prerequisite
      for biological sciences. It provides the means to describe and communicate about
      life without ambiguity. Current biological classification and nomenclature use
      the species as the basic unit and require lengthy and laborious species
      descriptions before newly discovered organisms can be assigned to a species and
      be named. The current system is thus inadequate to classify and name the immense
      genetic diversity within species that is now being revealed by genome sequencing
      on a daily basis. To address this lack of a general intra-species classification
      and naming system adequate for today's speed of discovery of new diversity, we
      propose a classification and naming system that is exclusively based on genome
      similarity and that is suitable for automatic assignment of codes to any genome
      sequenced organism without requiring any phenotypic or phylogenetic analysis. We
      provide examples demonstrating that genome similarity-based codes largely align
      with current taxonomic groups at many different levels in bacteria, animals,
      humans, plants, and viruses. Importantly, the proposed approach is only slightly
      affected by the order of code assignment and can thus provide codes that reflect
      similarity between organisms and that do not need to be revised upon discovery of
      new diversity. We envision genome similarity-based codes to complement current
      biological nomenclature and to provide a universal means to communicate
      unambiguously about any genome-sequenced organism in fields as diverse as
      biodiversity research, infectious disease control, human and microbial forensics,
      animal breed and plant cultivar certification, and human ancestry research. 

PMID- 24586552
TI  - Biochemical characterization of a haloalkane dehalogenase DadB from Alcanivorax
      dieselolei B-5.
AB  - Recently, we found that Alcanivorax bacteria from various marine environments
      were capable of degrading halogenated alkanes. Genome sequencing of A. dieselolei
      B-5 revealed two putative haloalkane dehalogenase (HLD) genes, which were
      supposed to be involved in degradation of halogenated compounds. In this report,
      we confirm for the first time that the Alcanivorax bacterium encodes a truly
      functional HLD named DadB. An activity assay with 46 halogenated substrates
      indicated that DadB possesses broad substrate range and has the highest overall
      activity among the identified HLDs. DadB prefers brominated substrates;
      chlorinated alkenes; and the C2-C3 substrates, including the persistent
      pollutants of 1,2-dichloroethane, 1,2-dichloropropane and 1,2,3-trichloropropane.
      As DadB displays no detectable activity toward long-chain haloalkanes such as 1
      chlorohexadecane and 1-chlorooctadecane, the degradation of them in A. dieselolei
      B-5 might be attributed to other enzymes. Kinetic constants were determined with
      6 substrates. DadB has highest affinity and largest k cat/K m value toward 1,3
      dibromopropane (K(m) = 0.82 mM, k(cat)/K(m) = 16.43 mM(-1) . s(-1)). DadB
      aggregates fast in the buffers with pH <= 7.0, while keeps stable in monomer form
      when pH >= 7.5. According to homology modeling, DadB has an open active cavity
      with a large access tunnel, which is supposed important for larger molecules as
      opposed to C2-C3 substrates. Combined with the results for other HLDs, we deduce
      that residue I247 plays an important role in substrate selection. These results
      suggest that DadB and its host, A. dieselolei B-5, are of potential use for
      biocatalysis and bioremediation applications.

PMID- 24586553
TI  - Angiopoietin1 inhibits mast cell activation and protects against anaphylaxis.
AB  - Since morbidity and mortality rates of anaphylaxis diseases have been increasing
      year by year, how to prevent and manage these diseases effectively has become an
      important issue. Mast cells play a central regulatory role in allergic diseases.
      Angiopoietin1 (Ang-1) exhibits anti-inflammatory properties by inhibiting
      vascular permeability, leukocyte migration and cytokine production. However, Ang
      1's function in mast cell activation and anaphylaxis diseases is unknown. The
      results of our study suggest that Ang-1 decreased lipopolysaccharide (LPS)
      induced pro-inflammatory cytokines production of mast cells by suppressing
      IkappaB phosphorylation and NF-kappaB nuclear translocation. Ang-1 also strongly
      inhibited compound 48/80 induced and FcepsilonRI-mediated mast cells
      degranulation by decreasing intracellular calcium levels in vitro. In vivo
      lentivirus-mediated delivery of Ang-1 in mice exhibited alleviated leakage in IgE
      dependent passive cutaneous anaphylaxis (PCA). Furthermore, exogenous Ang-1
      intervention treatment prevented mice from compound 48/80-induced mesentery mast
      cell degranulation, attenuated increases in pro-inflammatory cytokines, relieved
      lung injury, and improved survival in anaphylaxis shock. The results of our study
      reveal, for the first time, the important role of Ang-1 in the activation of mast
      cells, and identify a therapeutic effect of Ang-1 on anaphylaxis diseases. 

PMID- 24586555
TI  - Analogy, cognitive architecture and universal construction: a tale of two
      systematicities.
AB  - Cognitive science recognizes two kinds of systematicity: (1) as the property
      where certain cognitive capacities imply certain other related cognitive
      capacities (Fodor and Pylyshyn); and (2) as the principle that analogical
      mappings based on collections of connected relations are preferred over relations
      in isolation (Gentner). Whether these kinds of systematicity are two aspects of a
      deeper property of cognition is hitherto unknown. Here, it is shown that both
      derive from the formal, category-theoretic notion of universal construction. In
      conceptual/psychological terms, a universal construction is a form of
      optimization of cognitive resources: optimizing the re-utilization of common
      component processes for common task components. Systematic cognitive capacity and
      the capacity for analogy are hallmarks of human cognition, which suggests that
      universal constructions (in the category-theoretic sense) are a crucial component
      of human cognitive architecture.

PMID- 24586554
TI  - Pregnancy outcomes in liver and cardiothoracic transplant recipients: a UK
      national cohort study.
AB  - INTRODUCTION: There are an increasing number of reports of pregnancy in
      transplant recipients but many questions remain regarding the effect of the
      transplant on pregnancy outcome, the pregnancy on the graft and the medication on
      the fetus. The majority of studies reporting outcomes in transplant recipients
      have focused on women with kidney transplants, and have included retrospective,
      voluntary registries or single centre studies. METHODS: The UK Obstetric
      Surveillance System (UKOSS) was used to prospectively identify all pregnant women
      with a liver or cardiothoracic transplant in the United Kingdom, between January
      2007 and January 2012. Data were collected on demographics, transplant
      characteristics, immunosuppression regimens, antenatal care, maternal, graft and
      neonatal outcomes. In an exploratory analysis, we tested for associations between
      "poor fetal outcome" and medications used before or during pregnancy. RESULTS AND
      CONCLUSIONS: We report 62 pregnancies in 56 liver transplant recipients and 14
      pregnancies in 14 cardiothoracic transplant recipients (including 10 heart, three
      lung and one heart-lung recipient). Liver transplant recipients, in comparison to
      cardiothoracic, had similar livebirth rates (92% vs. 87%) but better fetal
      outcomes (median gestational age 38 weeks vs. 35 weeks; median birthweight 2698 g
      vs. 2365 g), fewer caesarean deliveries (47% vs. 62%), fewer maternal intensive
      care (ICU) admissions (19% vs. 29%) and fewer neonatal ICU admissions (25% vs.
      54%). Nine women (12%) were taking mycophenolate mofetil at conception, which was
      associated with adverse fetal outcomes. Pregnancy in transplant recipients may
      have successful outcomes, but complication rates are high, emphasising the role
      of pre-conception counselling and further research into the long-term effect on
      maternal and graft survival rates.

PMID- 24586556
TI  - Increased behavioral and neuronal responses to a hallucinogenic drug in PACAP
      heterozygous mutant mice.
AB  - Accumulating evidence from human genetic studies implicates the pituitary
      adenylate cyclase-activating polypeptide (PACAP) gene as a risk factor for
      psychiatric disorders, including schizophrenia and stress-related diseases. Mice
      with homozygous disruption of the PACAP gene display profound behavioral and
      neurological abnormalities that are ameliorated with the atypical antipsychotic
      and dopamine D2 and serotonin (5-HT)2 antagonist risperidone and the 5-HT2
      receptor antagonist ritanserin; however, the underlying mechanisms remain
      unknown. Here, we investigated if PACAP heterozygous mutant (PACAP(+/-)) mice,
      which appear behaviorally normal, are vulnerable to aversive stimuli. PACAP(+/-)
      mice were administered a 5-HT2 receptor agonist, (+/-)-2,5-dimethoxy-4
      iodoamphetamine (DOI), a hallucinogenic drug, and their responses were compared
      with the littermate wild-type mice. After DOI injection, PACAP(+/-) mice showed
      increased head-twitch responses, while their behavior was normal after saline.
      DOI induced deficits in sensorimotor gating, as determined by prepulse
      inhibition, specifically in PACAP(+/-) mice. However, other 5-HT2 receptor
      dependent responses, such as corticosterone release and hypothermia, were
      similarly observed in PACAP(+/-) and wild-type mice. c-Fos expression analysis,
      performed in various brain regions, revealed that the DOI-induced increase in the
      number of c-Fos-positive cells was more pronounced in 5-HT2A receptor-negative
      cells in the somatosensory cortex in PACAP(+/-) mice compared with wild-type
      mice. These results indicate that PACAP(+/-) mice exhibit specific vulnerability
      to DOI-induced deficits in cortical sensory function, such as exaggerated head
      twitch responses and sensorimotor gating deficits. Our findings provide insight
      into the neural mechanisms underlying impaired behavioral responses in which 5
      HT2 receptors are implicated.

PMID- 24586557
TI  - Mini-flank supra-12th rib incision for open partial nephrectomy compared with
      laparoscopic partial nephrectomy and traditional open partial nephrectomy.
AB  - PURPOSE: The purpose of this study was to report our approach of partial
      nephrectomy (PN) using a supra-12th rib mini-flank incision. We compared mini
      incision open partial nephrectomy (MI-OPN) with open partial nephrectomy (OPN)
      and laparoscopic partial nephrectomy (LPN) to verify whether MI-OPN can be an
      alternative to OPN and LPN. METHODS: This was a retrospective single-center study
      including 194 patients who underwent partial nephrectomy (PN) between February
      2005 and December 2010. Demographic, perioperative, and complication data were
      compared among the MI-OPN group, OPN group and LPN group. RESULTS: No statistical
      differences were reported in either group for age, sex, BMI, tumour side (right
      or left kidney), RENAL nephrometry scores, PADUA score and preoperative eGFR. The
      operative time was longer in LPN group when compared with MI-OPN and OPN group
      (all P<0.001). The warm ischemia time of LPN group was longer than MI-OPN group
      (P = 0.032) and OPN group (P = 0.005). The length of stay of LPN group was
      shorter than OPN group (P = 0.018), but was similar to MI-OPN group (P = 0.094).
      The incidence of renal artery clamping was lower in OPN group when compared with
      MI-OPN and LPN group (all P<0.001). More estimated blood loss was found in OPN
      group when compared with MI-OPN group (p = 0.003) and LPN group (P = 0.014). The
      overall incidence of postoperative complications was similar. CONCLUSIONS: The
      approach of MI-OPN can couple the benefits of both minimally invasive and open
      partial nephrectomy techniques with less estimated blood loss, shorter operative
      time, shorter length of stay, less postoperative complications, and a smaller
      incision. MI-OPN may be an effective alternative to laparoscopic or traditional
      open approaches, which maybe more suitable for the tumors with high RENAL
      nephrometry score or PADUA score.

PMID- 24586558
TI  - Perceptions of rule-breaking related to marine ecosystem health.
AB  - Finding effective solutions to manage marine resources is high on political and
      conservation agendas worldwide. This is made more urgent by the rate of increase
      in the human population and concomitant resource pressures in coastal areas. This
      paper links empirical socio-economic data about perceptions of marine resource
      health to the breaking of marine management rules, using fisheries as a case
      study. The relationship between perceived rule-breaking (non-compliance with
      regulations controlling fishing) and perceived health of inshore marine
      environments was investigated through face-to-face interviews with 299 heads of
      households in three Tanzanian coastal communities in November and December 2011.
      Awareness of rules controlling fishing activity was high among all respondents.
      Fishers were able to describe more specific rules controlling fishing practices
      than non-fishers (t = 3.5, df = 297, p<0.01). Perceived breaking of fishing
      regulations was reported by nearly half of all respondents, saying "some" (32% of
      responses) or "most" (15% of responses) people break fishing rules. Ordinal
      regression modelling revealed a significant linkage (z= -3.44, p<0.001) in the
      relationship between respondents' perceptions of deteriorating marine health and
      their perception of increased rule-breaking. In this paper, inferences from an
      empirical study are used to identify and argue the potential for using
      perceptions of ecosystem health and level of rule-breaking as a means to guide
      management measures. When considering different management options (e.g. Marine
      Protected Areas), policy makers are advised to take account of and utilise likely
      egoistic or altruistic decision-making factors used by fishers to determine their
      marine activities.

PMID- 24586559
TI  - Changes in voluntary activation assessed by transcranial magnetic stimulation
      during prolonged cycling exercise.
AB  - Maximal central motor drive is known to decrease during prolonged exercise
      although it remains to be determined whether a supraspinal deficit exists, and if
      so, when it appears. The purpose of this study was to evaluate corticospinal
      excitability and muscle voluntary activation before, during and after a 4-h
      cycling exercise. Ten healthy subjects performed three 80-min bouts on an
      ergocycle at 45% of their maximal aerobic power. Before exercise and immediately
      after each bout, neuromuscular function was evaluated in the quadriceps femoris
      muscles under isometric conditions. Transcranial magnetic stimulation was used to
      assess voluntary activation at the cortical level (VATMS), corticospinal
      excitability via motor-evoked potential (MEP) and intracortical inhibition by
      cortical silent period (CSP). Electrical stimulation of the femoral nerve was
      used to measure voluntary activation at the peripheral level (VAFNES) and muscle
      contractile properties. Maximal voluntary force was significantly reduced after
      the first bout (13 +/- 9%, P<0.01) and was further decreased (25 +/- 11%,
      P<0.001) at the end of exercise. CSP remained unchanged throughout the protocol.
      Rectus femoris and vastus lateralis but not vastus medialis MEP normalized to
      maximal M-wave amplitude significantly increased during cycling. Finally,
      significant decreases in both VATMS and VAFNES (~ 8%, P<0.05 and ~ 14%, P<0.001
      post-exercise, respectively) were observed. In conclusion, reductions in VAFNES
      after a prolonged cycling exercise are partly explained by a deficit at the
      cortical level accompanied by increased corticospinal excitability and unchanged
      intracortical inhibition. When comparing the present results with the literature,
      this study highlights that changes at the cortical and/or motoneuronal levels
      depend not only on the type of exercise (single-joint vs. whole-body) but also on
      exercise intensity and/or duration.

PMID- 24586560
TI  - Normalization of RNA-sequencing data from samples with varying mRNA levels.
AB  - Methods for normalization of RNA-sequencing gene expression data commonly assume
      equal total expression between compared samples. In contrast, scenarios of global
      gene expression shifts are many and increasing. Here we compare the performance
      of three normalization methods when polyA(+) RNA content fluctuates significantly
      during zebrafish early developmental stages. As a benchmark we have used reverse
      transcription-quantitative PCR. The results show that reads per kilobase per
      million (RPKM) and trimmed mean of M-values (TMM) normalization systematically
      leads to biased gene expression estimates. Biological scaling normalization
      (BSN), designed to handle differences in total expression, showed improved
      accuracy compared to the two other methods in estimating transcript level
      dynamics. The results have implications for past and future studies using RNA
      sequencing on samples with different levels of total or polyA(+) RNA. 

PMID- 24586561
TI  - Deletion of PREPl causes growth impairment and hypotonia in mice.
AB  - Genetic studies of rare diseases can identify genes of unknown function that
      strongly impact human physiology. Prolyl endopeptidase-like (PREPL) is an
      uncharacterized member of the prolyl peptidase family that was discovered because
      of its deletion in humans with hypotonia-cystinuria syndrome (HCS). HCS is
      characterized by a number of physiological changes including diminished growth
      and neonatal hypotonia or low muscle tone. HCS patients have deletions in other
      genes as well, making it difficult to tease apart the specific role of PREPL.
      Here, we develop a PREPL null (PREPL(-/-)) mouse model to address the
      physiological role of this enzyme. Deletion of exon 11 from the Prepl gene, which
      encodes key catalytic amino acids, leads to a loss of PREPL protein as well as
      lower Prepl mRNA levels. PREPL(-/-) mice have a pronounced growth phenotype,
      being significantly shorter and lighter than their wild type (PREPL(+/+))
      counterparts. A righting assay revealed that PREPL(-/-) pups took significantly
      longer than PREPL(+/+) pups to right themselves when placed on their backs. This
      deficit indicates that PREPL(-/-) mice suffer from neonatal hypotonia. According
      to these results, PREPL regulates growth and neonatal hypotonia in mice, which
      supports the idea that PREPL causes diminished growth and neonatal hypotonia in
      humans with HCS. These animals provide a valuable asset in deciphering the
      underlying biochemical, cellular and physiological pathways that link PREPL to
      HCS, and this may eventually lead to new insights in the treatment of this
      disease. 

PMID- 24586562
TI  - The ideal cardiovascular health metrics associated inversely with mortality from
      all causes and from cardiovascular diseases among adults in a Northern Chinese
      industrial city.
AB  - BACKGROUND AND AIMS: The American Heart Association has recently established
      seven ideal cardiovascular health metrics for cardiovascular health promotion and
      disease reduction (i.e., non-smoking, normal body mass index, physically active,
      healthy diet, and normal levels of cholesterol, blood pressure and fasting blood
      glucose). The present study seeks to evaluate how well these metrics predict
      mortality from all causes and cardiovascular diseases in adult Chinese living in
      a northern industrial city. METHODS AND RESULTS: Data of 95,429 adults who
      participated in the Kailuan cohort study from June 2006 to October 2007 was
      analyzed. All participants underwent questionnaire assessment, clinical
      examination, laboratory assessments and were followed up biannually. During a
      median follow-up of 4.02 years, 1,843 deaths occurred, with 597 deaths resulting
      from cardiovascular diseases. Lower mortality rates from all causes and
      cardiovascular diseases were observed among the subjects who met a higher number
      of the ideal health metrics. Compared to the participants who met none or one
      ideal health metric, those meeting >=5 ideal health metrics had a lower risk of
      all-cause mortality by 30% (adjusted hazard ratio, 0.70; 95% confidence interval,
      0.56-0.88) and a lower risk of mortality from cardiovascular diseases by 39%
      (adjusted hazard ratio, 0.61; 95% confidence interval, 0.41-0.89) . Four metrics
      (smoking status, physical activity, blood pressure and fasting blood glucose)
      were significantly associated with all-cause mortality. Three metrics (physical
      activity, blood pressure and fasting blood glucose) were significantly associated
      with mortality from cardiovascular diseases. CONCLUSION: The number of ideal
      health metrics is negatively associated with mortality rates from all causes and
      cardiovascular diseases among adults in a Northern Chinese industrial city. The
      data supports the AHA recommendation of ideal health metrics for adults from
      Northern China.

PMID- 24586563
TI  - ENZYMAP: exploiting protein annotation for modeling and predicting EC number
      changes in UniProt/Swiss-Prot.
AB  - The volume and diversity of biological data are increasing at very high rates.
      Vast amounts of protein sequences and structures, protein and genetic
      interactions and phenotype studies have been produced. The majority of data
      generated by high-throughput devices is automatically annotated because manually
      annotating them is not possible. Thus, efficient and precise automatic annotation
      methods are required to ensure the quality and reliability of both the biological
      data and associated annotations. We proposed ENZYMatic Annotation Predictor
      (ENZYMAP), a technique to characterize and predict EC number changes based on
      annotations from UniProt/Swiss-Prot using a supervised learning approach. We
      evaluated ENZYMAP experimentally, using test data sets from both UniProt/Swiss
      Prot and UniProt/TrEMBL, and showed that predicting EC changes using selected
      types of annotation is possible. Finally, we compared ENZYMAP and DETECT with
      respect to their predictions and checked both against the UniProt/Swiss-Prot
      annotations. ENZYMAP was shown to be more accurate than DETECT, coming closer to
      the actual changes in UniProt/Swiss-Prot. Our proposal is intended to be an
      automatic complementary method (that can be used together with other techniques
      like the ones based on protein sequence and structure) that helps to improve the
      quality and reliability of enzyme annotations over time, suggesting possible
      corrections, anticipating annotation changes and propagating the implicit
      knowledge for the whole dataset. 

PMID- 24586564
TI  - Prognostic relevance of urinary bladder cancer susceptibility loci.
AB  - In the last few years, susceptibility loci have been identified for urinary
      bladder cancer (UBC) through candidate-gene and genome-wide association studies.
      Prognostic relevance of most of these loci is yet unknown. In this study, we used
      data of the Nijmegen Bladder Cancer Study (NBCS) to perform a comprehensive
      evaluation of the prognostic relevance of all confirmed UBC susceptibility loci.
      Detailed clinical data concerning diagnosis, stage, treatment, and disease course
      of a population-based series of 1,602 UBC patients were collected retrospectively
      based on a medical file survey. Kaplan-Meier survival analyses and Cox
      proportional hazard regression were performed, and log-rank tests calculated, to
      evaluate the association between 12 confirmed UBC susceptibility variants and
      recurrence and progression in non-muscle invasive bladder cancer (NMIBC)
      patients. Among muscle-invasive or metastatic bladder cancer (MIBC) patients,
      association of these variants with overall survival was tested. Subgroup analyses
      by tumor aggressiveness and smoking status were performed in NMIBC patients. In
      the overall NMIBC group (n = 1,269), a statistically significant association
      between rs9642880 at 8q24 and risk of progression was observed (GT vs. TT: HR =
      1.08 (95% CI: 0.76-1.54), GG vs. TT: HR = 1.81 (95% CI: 1.23-2.66), P for trend =
      2.6 * 10(-3)). In subgroup analyses, several other variants showed suggestive,
      though non-significant, prognostic relevance for recurrence and progression in
      NMIBC and survival in MIBC. This study provides suggestive evidence that genetic
      loci involved in UBC etiology may influence disease prognosis. Elucidation of the
      causal variant(s) could further our understanding of the mechanism of disease,
      could point to new therapeutic targets, and might aid in improvement of
      prognostic tools.

PMID- 24586565
TI  - The origin and early evolution of Sauria: reassessing the permian Saurian fossil
      record and the timing of the crocodile-lizard divergence.
AB  - Sauria is the crown-group of Diapsida and is subdivided into Lepidosauromorpha
      and Archosauromorpha, comprising a high percentage of the diversity of living and
      fossil tetrapods. The split between lepidosauromorphs and archosauromorphs (the
      crocodile-lizard, or bird-lizard, divergence) is considered one of the key
      calibration points for molecular analyses of tetrapod phylogeny. Saurians have a
      very rich Mesozoic and Cenozoic fossil record, but their late Paleozoic (Permian)
      record is problematic. Several Permian specimens have been referred to Sauria,
      but the phylogenetic affinity of some of these records remains questionable. We
      reexamine and review all of these specimens here, providing new data on early
      saurian evolution including osteohistology, and present a new morphological
      phylogenetic dataset. We support previous studies that find that no valid Permian
      record for Lepidosauromorpha, and we also reject some of the previous referrals
      of Permian specimens to Archosauromorpha. The most informative Permian
      archosauromorph is Protorosaurus speneri from the middle Late Permian of Western
      Europe. A historically problematic specimen from the Late Permian of Tanzania is
      redescribed and reidentified as a new genus and species of basal archosauromorph:
      Aenigmastropheus parringtoni. The supposed protorosaur Eorasaurus olsoni from the
      Late Permian of Russia is recovered among Archosauriformes and may be the oldest
      known member of the group but the phylogenetic support for this position is low.
      The assignment of Archosaurus rossicus from the latest Permian of Russia to the
      archosauromorph clade Proterosuchidae is supported. Our revision suggests a
      minimum fossil calibration date for the crocodile-lizard split of 254.7 Ma. The
      occurrences of basal archosauromorphs in the northern (30 degrees N) and southern
      (55 degrees S) parts of Pangea imply a wider paleobiogeographic distribution for
      the group during the Late Permian than previously appreciated. Early
      archosauromorph growth strategies appear to be more diverse than previously
      suggested based on new data on the osteohistology of Aenigmastropheus. 

PMID- 24586566
TI  - Genetic polymorphism of apolipoprotein A5 gene and susceptibility to type 2
      diabetes mellitus: a meta-analysis of 15,137 subjects.
AB  - BACKGROUND: Several studies have investigated whether the polymorphism in the
      apolipoprotein A5 (APOA5) is associated with type 2 diabetes mellitus (T2DM)
      risk. However, those studies have produced inconsistent results. The purpose of
      this study was to investigate whether the APOA5 -1131T/C polymorphism (rs662799)
      confers significant susceptibility to T2DM using a meta-analysis. METHODS:
      PubMed, Embase, Web of Science, Cochrane database, CBMdisc, CNKI and Google
      Scholar were searched to get the genetic association studies. All statistical
      analyses were done with Stata 11.0. RESULTS: A total of 19 studies included 4,767
      T2DM cases and 10,370 controls (four studies involving 555 T2DM cases and 2958
      controls were performed among Europeans and 15 studies involving 4212 T2DM cases
      and 7412 controls were performed among Asians) were combined showing significant
      association between the APOA5 -1131T/C polymorphism and T2DM risk (for C allele
      vs. T allele: OR = 1.28, 95% CI = 1.17-1.40, p<0.00001; for C/C vs. T/T: OR =
      1.57, 95% CI = 1.35-1.83, p<0.00001; for C/C vs. T/C+T/T: OR = 1.36, 95% CI =
      1.18-1.57, p<0.0001; for C/C+T/C vs. T/T: OR = 1.32, 95% CI = 1.16-1.51,
      p<0.0001). In the subgroup analysis by ethnicity, significant association was
      also found among Asians (for C allele vs. T allele: OR = 1.31, 95% CI = 1.22
      1.40, p<0.00001; for C/C vs. T/T: OR = 1.61, 95% CI = 1.38-1.88, p<0.00001; for
      C/C vs. T/C+T/T: OR = 1.39, 95% CI = 1.20-1.61, p<0.0001; for C/C+T/C vs. T/T: OR
      = 1.42, 95% CI = 1.25-1.62, p<0.00001). However, no significant association was
      found between the APOA5 -1131T/C polymorphism and T2DM risk among Europeans.
      CONCLUSIONS: The present meta-analysis suggests that the APOA5 -1131T/C
      polymorphism is associated with an increased T2DM risk in Asian population.

PMID- 24586568
TI  - Adiponectin gene polymorphisms and acute respiratory distress syndrome
      susceptibility and mortality.
AB  - RATIONALE: Adiponectin is an anti-inflammatory adipokine that is the most
      abundant gene product of adipose tissue. Lower levels have been observed in
      obesity, insulin resistance, and in critical illness. However, elevated levels
      early in acute respiratory failure have been associated with mortality.
      Polymorphisms in adiponectin-related genes (ADIPOQ, ADIPOR1, ADIPOR2) have been
      examined for relationships with obesity, insulin resistance and diabetes,
      cardiovascular disease, and to circulating adipokine levels, but many gaps in
      knowledge remain. The current study aims to assess the association between
      potentially functional polymorphisms in adiponectin-related genes with acute
      respiratory distress syndrome (ARDS) risk and mortality. METHODS: Consecutive
      patients with risk factors for ARDS admitted to the ICU were enrolled and
      followed prospectively for development of ARDS. ARDS cases were followed through
      day 60 for all-cause mortality. 2067 patients were successfully genotyped using
      the Illumina CVD BeadChip high-density platform. Of these, 567 patients developed
      ARDS. Forty-four single nucleotide polymorphisms (SNPs) on ADIPOQ, ADIPOR1 and
      ADIPOR2 were successfully genotyped. Of these, 9 SNPs were hypothesized to be
      functional based on their location (promoter, exon, or 3' untranslated region).
      These 9 SNPs were analyzed for association with ARDS case status and mortality
      among ARDS cases. RESULTS: After multivariable analysis and adjustment for
      multiple comparisons, no SNPs were significantly associated with ARDS case
      status. Among ARDS cases, homozygotes for the minor allele of rs2082940 (ADIPOQ)
      had increased mortality (hazard ratio 2.61, 95% confidence interval 1.36-5.00, p
      = 0.0039) after adjustment for significant covariates. The significance of this
      association persisted after adjustment for multiple comparisons (FDR_q = 0.029).
      CONCLUSIONS: A common and potentially functional polymorphism in ADIPOQ may
      impact survival in ARDS. Further studies are required to replicate these results
      and to correlate genotype with circulating adiponectin levels.

PMID- 24586567
TI  - Novel CoQ10 antidiabetic mechanisms underlie its positive effect: modulation of
      insulin and adiponectine receptors, Tyrosine kinase, PI3K, glucose transporters,
      sRAGE and visfatin in insulin resistant/diabetic rats.
AB  - As a nutritional supplement, coenzyme Q10 (CoQ10) was tested previously in
      several models of diabetes and/or insulin resistance (IR); however, its exact
      mechanisms have not been profoundly explicated. Hence, the objective of this work
      is to verify some of the possible mechanisms that underlie its therapeutic
      efficacy. Moreover, the study aimed to assess the potential modulatory effect of
      CoQ10 on the antidiabetic action of glimebiride. An insulin resistance/type 2
      diabetic model was adopted, in which rats were fed high fat/high fructose diet
      (HFFD) for 6 weeks followed by a single sub-diabetogenic dose of streptozotocin
      (35 mg/kg, i.p.). At the end of the 7(th) week animals were treated with CoQ10
      (20 mg/kg, p.o) and/or glimebiride (0.5 mg/kg, p.o) for 2 weeks. CoQ10 alone
      opposed the HFFD effect and increased the hepatic/muscular content/activity of
      tyrosine kinase (TK), phosphatidylinositol kinase (PI3K), and adiponectin
      receptors. Conversely, it decreased the content/activity of insulin receptor
      isoforms, myeloperoxidase and glucose transporters (GLUT4; 2). Besides, it
      lowered significantly the serum levels of glucose, insulin, fructosamine and HOMA
      index, improved the serum lipid panel and elevated the levels of glutathione,
      sRAGE and adiponectin. On the other hand, CoQ10 lowered the serum levels of
      malondialdehyde, visfatin, ALT and AST. Surprisingly, CoQ10 effect surpassed that
      of glimepiride in almost all the assessed parameters, except for glucose,
      fructosamine, TK, PI3K, and GLUT4. Combining CoQ10 with glimepiride enhanced the
      effect of the latter on the aforementioned parameters. CONCLUSION: These results
      provided a new insight into the possible mechanisms by which CoQ10 improves
      insulin sensitivity and adjusts type 2 diabetic disorder. These mechanisms
      involve modulation of insulin and adiponectin receptors, as well as TK, PI3K,
      glucose transporters, besides improving lipid profile, redox system, sRAGE, and
      adipocytokines. The study also points to the potential positive effect of CoQ10
      as an adds- on to conventional antidiabetic therapies.

PMID- 24586570
TI  - Estrogen receptor-negative breast ductal carcinoma: clinicopathological features
      and MIB-1 (Ki-67) proliferative index association.
AB  - Breast cancer estrogen receptor (ER) status is one of the strong additional
      factors in predicting response of patients towards hormonal treatment. The main
      aim of this study was to assess the morphological characteristics and
      proliferative activity using MIB-1(Ki-67) of estrogen receptor negative invasive
      breast ductal carcinoma (NOS type) as well as to correlate these features with
      clinicopathological data. We also aim to study the expression of c-erbB2 in ER
      negative breast tumors. High proliferative rate (MIB-1 above 20%) was observed in
      63 (63.6%) of 99 ER negative tumors and that these tumors were associated with
      high expression of c-erbB2 (57.6%). We observed that MIB-1 is a reliable
      independent prognostic indicator for ER negative infiltrating ductal carcinoma in
      this study. 

PMID- 24586569
TI  - Transperineal ultrasound-guided 12-core prostate biopsy: an extended approach to
      diagnose transition zone prostate tumors.
AB  - OBJECTIVE: Transperineal ultrasound-guided (TPUS) 12-core prostate biopsy was
      evaluated as an initial strategy for the diagnosis of prostate cancer, The
      distribution of prostate cancer lesions was assessed with zone-specific biopsy.
      METHODS: From January 2010 to December 2012, 287 patients underwent TPUS-guided
      12-core prostate biopsy. Multiple cores were obtained from both the peripheral
      zone (PZ) and the transition zone (TZ) of the prostate. Participants' clinical
      data and the diagnostic yield of the cores were recorded and prospectively
      analyzed as a cross-sectional study. RESULTS: The diagnostic yield of the 12-core
      prostate biopsy was significantly higher compared to the 6-core scheme (42.16 vs.
      21.6%). The diagnostic yield of the 10-core prostate biopsy was significantly
      higher compared to the 6-core scheme (37.6 vs. 21.6%). The 12-core scheme
      improved the diagnostic yield in prostates >50 ml (12-core scheme: 28.1% vs. 10
      core scheme: 20.4%; p = 0.034). CONCLUSIONS: The 12-core biopsy scheme is a safe
      and effective approach for the diagnosis of prostate cancer. TZ biopsies in
      patients with larger prostates should be included in the initial biopsy strategy.

PMID- 24586571
TI  - Value assessment of ecosystem services in nature reserves in Ningxia, China: a
      response to ecological restoration.
AB  - Changes in land use can cause significant changes in the ecosystem structure and
      process variation of ecosystem services. This study presents a detailed spatial,
      quantitative assessment of the variation in the value of ecosystem services based
      on land use change in national nature reserves of the Ningxia autonomous region
      in China. We used areas of land use types calculated from the remote sensing data
      and the adjusted value coefficients to assess the value of ecosystem services for
      the years 2000, 2005, and 2010, analyzing the fluctuations in the valuation of
      ecosystem services in response to land use change. With increases in the areas of
      forest land and water bodies, the value of ecosystem services increased from
      182.3*10(7) to 223.8*10(7) US$ during 2000-2010. Grassland and forest land
      accounted for 90% of this increase. The values of all ecosystem services
      increased during this period, especially the value of ecosystem services for
      biodiversity protection and soil formation and protection. Ecological restoration
      in the reserves had a positive effect on the value of ecosystem services during
      2000-2010. 

PMID- 24586572
TI  - Effect of bodily fluids from honey bee (Apis mellifera) larvae on growth and
      genome-wide transcriptional response of the causal agent of American Foulbrood
      disease (Paenibacillus larvae).
AB  - Paenibacillus larvae, the causal agent of American Foulbrood disease (AFB),
      affects honey bee health worldwide. The present study investigates the effect of
      bodily fluids from honey bee larvae on growth velocity and transcription for this
      Gram-positive, endospore-forming bacterium. It was observed that larval fluids
      accelerate the growth and lead to higher bacterial densities during stationary
      phase. The genome-wide transcriptional response of in vitro cultures of P. larvae
      to larval fluids was studied by microarray technology. Early responses of P.
      larvae to larval fluids are characterized by a general down-regulation of
      oligopeptide and sugar transporter genes, as well as by amino acid and
      carbohydrate metabolic genes, among others. Late responses are dominated by
      general down-regulation of sporulation genes and up-regulation of phage-related
      genes. A theoretical mechanism of carbon catabolite repression is discussed. 

PMID- 24586574
TI  - The effects of anti-vaccine conspiracy theories on vaccination intentions.
AB  - The current studies investigated the potential impact of anti-vaccine conspiracy
      beliefs, and exposure to anti-vaccine conspiracy theories, on vaccination
      intentions. In Study 1, British parents completed a questionnaire measuring
      beliefs in anti-vaccine conspiracy theories and the likelihood that they would
      have a fictitious child vaccinated. Results revealed a significant negative
      relationship between anti-vaccine conspiracy beliefs and vaccination intentions.
      This effect was mediated by the perceived dangers of vaccines, and feelings of
      powerlessness, disillusionment and mistrust in authorities. In Study 2,
      participants were exposed to information that either supported or refuted anti
      vaccine conspiracy theories, or a control condition. Results revealed that
      participants who had been exposed to material supporting anti-vaccine conspiracy
      theories showed less intention to vaccinate than those in the anti-conspiracy
      condition or controls. This effect was mediated by the same variables as in Study
      1. These findings point to the potentially detrimental consequences of anti
      vaccine conspiracy theories, and highlight their potential role in shaping health
      related behaviors. 

PMID- 24586573
TI  - Synthesis and properties of a selective inhibitor of homeodomain-interacting
      protein kinase 2 (HIPK2).
AB  - Homeodomain-interacting protein kinase 2 (HIPK2) is a Ser/Thr kinase controlling
      cell proliferation and survival, whose investigation has been hampered by the
      lack of specific inhibitors able to dissect its cellular functions. SB203580, a
      p38 MAP kinase inhibitor, has been used as a tool to inhibit HIPK2 in cells, but
      here we show that its efficacy as HIPK2 inhibitor is negligible (IC50>40 uM). In
      contrast by altering the scaffold of the promiscuous CK2 inhibitor TBI a new
      class of HIPK2 inhibitors has been generated. One of these, TBID, displays toward
      HIPK2 unprecedented efficacy (IC50 = 0.33 uM) and selectivity (Gini coefficient
      0.592 out of a panel of 76 kinases). The two other members of the HIPK family,
      HIPK1 and HIPK3, are also inhibited by TBID albeit less efficiently than HIPK2.
      The mode of action of TBID is competitive with respect to ATP, consistent with
      modelling. We also provide evidence that TBID is cell permeable by showing that
      HIPK2 activity is reduced in cells treated with TBID, although with an IC50 two
      orders of magnitude higher (about 50 uM) than in vitro.

PMID- 24586575
TI  - Prediction of clinical factors associated with pandemic influenza A (H1N1) 2009
      in Pakistan.
AB  - BACKGROUND: Influenza is a viral infection that can lead to serious complications
      and death(s) in vulnerable groups if not diagnosed and managed in a timely
      manner. This study was conducted to improve the accuracy of predicting influenza
      through various clinical and statistical models. METHODOLOGY: A retrospective
      cross sectional analysis was done on demographic and epidemiological data
      collected from March 2009 to March 2010. Patients were classified as ILI or SARI
      using WHO case definitions. Respiratory specimens were tested by RT-PCR. Clinical
      symptoms and co-morbid conditions were analyzed using binary logistic regression
      models. RESULTS: In the first approach, analysis compared children (<=12) and
      adults (>12). Of 1,243 cases, 262 (21%) tested positive for A(H1N1)pdm09 and the
      proportion of children (<=12) and adults (>12) were 27% and 73% respectively.
      Four symptoms predicted influenza in children: fever (OR 2.849, 95% CI 1.931
      8.722), cough (OR 1.99, 95% CI 1.512-3.643), diarrhea (OR 2.100, 95% CI 2.040
      3.25) and respiratory disease (OR 3.269, 95% CI 2.128-12.624). In adults, the
      strongest clinical predictor was fever (OR 2.80, 95% CI 1.025-3.135) followed by
      cough (OR 1.431, 95% CI 1.032-2.815). In the second instance, patients were
      separated into two groups: SARI 326 (26%) and ILI 917 (74%) cases. Male to female
      ratio was 1.41?1.12 for SARI and 2?1.5 for ILI cases. Chi-square test showed that
      fever, cough and sore throat were significant factors for A(H1N1)pdm09 infections
      (p = 0.008). CONCLUSION: Studies in a primary care setting should be encouraged
      focused on patients with influenza-like illness to develop sensitive clinical
      case definition that will help to improve accuracy of detecting influenza
      infections. Formulation of a standard "one size fits all" case definition that
      best correlates with influenza infections can help guide decisions for additional
      diagnostic testing and also discourage unjustified antibiotic prescription and
      usage in clinical practice.

PMID- 24586576
TI  - TGF-beta prevents phosphate-induced osteogenesis through inhibition of BMP and
      Wnt/beta-catenin pathways.
AB  - BACKGROUND: Transforming growth factor-beta (TGF-beta) is a key cytokine during
      differentiation of mesenchymal stem cells (MSC) into vascular smooth muscle cells
      (VSMC). High phosphate induces a phenotypic transformation of vascular smooth
      muscle cells (VSMC) into osteogenic-like cells. This study was aimed to evaluate
      signaling pathways involved during VSMC differentiation of MSC in presence or not
      of high phosphate. RESULTS: Our results showed that TGF-beta induced nuclear
      translocation of Smad3 as well as the expression of vascular smooth muscle
      markers, such as smooth muscle alpha actin, SM22alpha, myocardin, and smooth
      muscle-myosin heavy chain. The addition of high phosphate to MSC promoted nuclear
      translocation of Smad1/5/8 and the activation of canonical Wnt/beta-catenin in
      addition to an increase in BMP-2 expression, calcium deposition and alkaline
      phosphatase activity. The administration of TGF-beta to MSC treated with high
      phosphate abolished all these effects by inhibiting canonical Wnt, BMP and TGF
      beta pathways. A similar outcome was observed in high phosphate-treated cells
      after the inhibition of canonical Wnt signaling with Dkk-1. Conversely, addition
      of both Wnt/beta-catenin activators CHIR98014 and lithium chloride enhanced the
      effect of high phosphate on BMP-2, calcium deposition and alkaline phosphatase
      activity. CONCLUSIONS: Full VSMC differentiation induced by TGF-beta may not be
      achieved when extracellular phosphate levels are high. Moreover, TGF-beta
      prevents high phosphate-induced osteogenesis by decreasing the nuclear
      translocation of Smad 1/5/8 and avoiding the activation of Wnt/beta-catenin
      pathway.

PMID- 24586577
TI  - Effects of physician-nurse substitution on clinical parameters: a systematic
      review and meta-analysis.
AB  - BACKGROUND: Physicians' shortage in many countries and demands of high-quality
      and affordable care make physician-nurse substitution an appealing workforce
      strategy. The objective of this study is to conduct a systematic review and meta
      analysis of randomised controlled trials (RCTs) assessing the impact of physician
      nurse substitution in primary care on clinical parameters. METHODS: We
      systematically searched OVID Medline and Embase, The Cochrane Library and CINAHL,
      up to August 2012; selected peer-reviewed RCTs comparing physician-led care with
      nurse-led care on changes in clinical parameters. Study selection and data
      extraction were performed in duplicate by independent reviewers. We assessed the
      individual study risk of bias; calculated the study-specific and pooled relative
      risks (RR) or weighted mean differences (WMD); and performed fixed-effects meta
      analyses. RESULTS: 11 RCTs (N = 30,247) were included; most were from Europe,
      generally small with higher risk of bias. In all studies, nurses provided care
      for complex conditions including HIV, hypertension, heart failure,
      cerebrovascular diseases, diabetes, asthma, Parkinson's disease and incontinence.
      Meta-analyses showed greater reductions in systolic blood pressure (SBP) in
      favour of nurse-led care (WMD -4.27 mmHg, 95% CI -6.31 to -2.23) but no
      statistically significant differences between groups in the reduction of
      diastolic blood pressure (DBP) (WMD -1.48 mmHg, 95%CI -3.05 to -0.09), total
      cholesterol (TC) (WMD -0.08 mmol/l, 95%CI -0.22 to 0.07) or glycosylated
      haemoglobin (WMD 0.12%HbAc1, 95%CI -0.13 to 0.37). Of other 32 clinical
      parameters identified, less than a fifth favoured nurse-led care while 25 showed
      no significant differences between groups. LIMITATIONS: disease-specific
      interventions from a small selection of healthcare systems, insufficient quantity
      and quality of studies, many different parameters. CONCLUSIONS: trained nurses
      appeared to be better than physicians at lowering SBP but similar at lowering
      DBP, TC or HbA1c. There is insufficient evidence that nurse-led care leads to
      better outcomes of other clinical parameters than physician-led care.

PMID- 24586578
TI  - Configuration of fibrous and adipose tissues in the cavernous sinus.
AB  - OBJECTIVE: Three-dimensional anatomical appreciation of the matrix of the
      cavernous sinus is one of the crucial necessities for a better understanding of
      tissue patterning and various disorders in the sinus. The purpose of this study
      was to reveal configuration of fibrous and adipose components in the cavernous
      sinus and their relationship with the cranial nerves and vessels in the sinus and
      meningeal sinus wall. MATERIALS AND METHODS: Nineteen cadavers (8 females and 11
      males; age range, 54-89 years; mean age, 75 years) were prepared as transverse (6
      sets), coronal (3 sets) and sagittal (10 sets) plastinated sections that were
      examined at both macroscopic and microscopic levels. RESULTS: Two types of the
      web-like fibrous networks were identified and localized in the cavernous sinus. A
      dural trabecular network constituted a skeleton-frame in the sinus and
      contributed to the sleeves of intracavernous cranial nerves III, IV, V1, V2 and
      VI. A fine trabecular network, or adipose tissue, was the matrix of the sinus and
      was mainly distributed along the medial side of the intracavernous cranial
      nerves, forming a dumbbell-shaped adipose zone in the sinus. CONCLUSIONS: This
      study revealed the nature, fine architecture and localization of the fine and
      dural trabecular networks in the cavernous sinus and their relationship with
      intracavernous cranial nerves and vessels. The results may be valuable for better
      understanding of tissue patterning in the cranial base and better evaluation of
      intracavernous disorders, e.g. the growth direction and extent of intracavernous
      tumors.

PMID- 24586580
TI  - Comparing distributions of color words: pitfalls and metric choices.
AB  - Computational methods have started playing a significant role in semantic
      analysis. One particularly accessible area for developing good computational
      methods for linguistic semantics is in color naming, where perceptual
      dissimilarity measures provide a geometric setting for the analyses. This setting
      has been studied first by Berlin & Kay in 1969, and then later on by a large data
      collection effort: the World Color Survey (WCS). From the WCS, a dataset on color
      naming by 2 616 speakers of 110 different languages is made available for further
      research. In the analysis of color naming from WCS, however, the choice of
      analysis method is an important factor of the analysis. We demonstrate concrete
      problems with the choice of metrics made in recent analyses of WCS data, and
      offer approaches for dealing with the problems we can identify. Picking a metric
      for the space of color naming distributions that ignores perceptual distances
      between colors assumes a decorrelated system, where strong spatial correlations
      in fact exist. We can demonstrate that the corresponding issues are significantly
      improved when using Earth Mover's Distance, or Quadratic [Formula: see text]
      square Distance, and we can approximate these solutions with a kernel-based
      analysis method. 

PMID- 24586579
TI  - Growth differentiation factor 6 as a putative risk factor in neuromuscular
      degeneration.
AB  - Mutation of Glass bottom boat, the Drosophila homologue of the bone morphogenetic
      protein or growth/differentiation factor (BMP/GDF) family of genes in
      vertebrates, has been shown to disrupt development of neuromuscular junctions
      (NMJ). Here we tested whether this same conclusion can be broadened to vertebrate
      BMP/GDF genes. This analysis was also extended to consider whether such genes are
      required for NMJ maintenance in post-larval stages, as this would argue that BMP
      genes are viable candidates for analysis in progressive neuromuscular disease.
      Zebrafish mutants harboring homozygous null mutations in the BMP-family gene
      gdf6a were raised to adulthood and assessed for neuromuscular deficits. Fish
      lacking gdf6a exhibited decreased endurance (~ 50%, p = 0.005) compared to wild
      type, and this deficit progressively worsened with age. These fish also presented
      with significantly disrupted NMJ morphology (p = 0.009), and a lower abundance of
      spinal motor neurons (~ 50%, p<0.001) compared to wild type. Noting the
      similarity of these symptoms to those of Amyotrophic Lateral Sclerosis (ALS)
      model mice and fish, we asked if mutations in gdf6a would enhance the phenotypes
      observed in the latter, i.e. in zebrafish over-expressing mutant Superoxide
      Dismutase 1 (SOD1). Amongst younger adult fish only bigenic fish harboring both
      the SOD1 transgene and gdf6a mutations, but not siblings with other combinations
      of these gene modifications, displayed significantly reduced endurance (75%,
      p<0.05) and strength/power (75%, p<0.05), as well as disrupted NMJ morphology
      (p<0.001) compared to wild type siblings. Bigenic fish also had lower survival
      rates compared to other genotypes. Thus conclusions regarding a role for BMP
      ligands in effecting NMJ can be extended to vertebrates, supporting conservation
      of mechanisms relevant to neuromuscular degenerative diseases. These conclusions
      synergize with past findings to argue for further analysis of GDF6 and other BMP
      genes as modifier loci, potentially affecting susceptibility to ALS and perhaps a
      broader suite of neurodegenerative diseases.

PMID- 24586581
TI  - Risk factors for hospital admission with RSV bronchiolitis in England: a
      population-based birth cohort study.
AB  - OBJECTIVE: To examine the timing and duration of RSV bronchiolitis hospital
      admission among term and preterm infants in England and to identify risk factors
      for bronchiolitis admission. DESIGN: A population-based birth cohort with follow
      up to age 1 year, using the Hospital Episode Statistics database. SETTING: 71
      hospitals across England. PARTICIPANTS: We identified 296618 individual birth
      records from 2007/08 and linked to subsequent hospital admission records during
      the first year of life. RESULTS: In our cohort there were 7189 hospital
      admissions with a diagnosis of bronchiolitis, 24.2 admissions per 1000 infants
      under 1 year (95%CI 23.7-24.8), of which 15% (1050/7189) were born preterm (47.3
      bronchiolitis admissions per 1000 preterm infants (95% CI 44.4-50.2)). The peak
      age group for bronchiolitis admissions was infants aged 1 month and the median
      was age 120 days (IQR = 61-209 days). The median length of stay was 1 day (IQR =
      0-3). The relative risk (RR) of a bronchiolitis admission was higher among
      infants with known risk factors for severe RSV infection, including those born
      preterm (RR = 1.9, 95% CI 1.8-2.0) compared with infants born at term. Other
      conditions also significantly increased risk of bronchiolitis admission,
      including Down's syndrome (RR = 2.5, 95% CI 1.7-3.7) and cerebral palsy (RR =
      2.4, 95% CI 1.5-4.0). CONCLUSIONS: Most (85%) of the infants who are admitted to
      hospital with bronchiolitis in England are born at term, with no known
      predisposing risk factors for severe RSV infection, although risk of admission is
      higher in known risk groups. The early age of bronchiolitis admissions has
      important implications for the potential impact and timing of future active and
      passive immunisations. More research is needed to explain why babies born with
      Down's syndrome and cerebral palsy are also at higher risk of hospital admission
      with RSV bronchiolitis.

PMID- 24586582
TI  - Miz1 deficiency in the mammary gland causes a lactation defect by attenuated
      Stat5 expression and phosphorylation.
AB  - Miz1 is a zinc finger transcription factor with an N-terminal POZ domain.
      Complexes with Myc, Bcl-6 or Gfi-1 repress expression of genes like Cdkn2b
      (p15(Ink4)) or Cdkn1a (p21(Cip1)). The role of Miz1 in normal mammary gland
      development has not been addressed so far. Conditional knockout of the Miz1 POZ
      domain in luminal cells during pregnancy caused a lactation defect with a
      transient reduction of glandular tissue, reduced proliferation and attenuated
      differentiation. This was recapitulated in vitro using mouse mammary gland
      derived HC11 cells. Further analysis revealed decreased Stat5 activity in
      Miz1DeltaPOZ mammary glands and an attenuated expression of Stat5 targets. Gene
      expression of the Prolactin receptor (PrlR) and ErbB4, both critical for Stat5
      phosphorylation (pStat5) or pStat5 nuclear translocation, was decreased in
      Miz1DeltaPOZ females. Microarray, ChIP-Seq and gene set enrichment analysis
      revealed a down-regulation of Miz1 target genes being involved in vesicular
      transport processes. Our data suggest that deranged intracellular transport and
      localization of PrlR and ErbB4 disrupt the Stat5 signalling pathway in mutant
      glands and cause the observed lactation phenotype. 

PMID- 24586583
TI  - Molecular genotyping of anisakis larvae in Middle Eastern Japan and endoscopic
      evidence for preferential penetration of normal over atrophic mucosa.
AB  - BACKGROUND: Anisakiasis is a parasitic disease caused primarily by Anisakis spp.
      larvae in Asia and in Western countries. The aim of this study was to investigate
      the genotype of Anisakis larvae endoscopically removed from Middle Eastern
      Japanese patients and to determine whether mucosal atrophy affects the risk of
      penetration in gastric anisakiasis. METHODS: In this study, 57 larvae collected
      from 44 patients with anisakiasis (42 gastric and 2 colonic anisakiasis) were
      analyzed retrospectively. Genotyping was confirmed by restriction fragment length
      polymorphism (RFLP) analysis of ITS regions and by sequencing the mitochondrial
      small subunit (SSU) region. In the cases of gastric anisakiasis, correlation
      analyses were conducted between the frequency of larval penetration in
      normal/atrophic area and the manifestation of clinical symptoms. RESULTS: Nearly
      all larvae were A. simplex seusu stricto (s.s.) (99%), and one larva displayed a
      hybrid genotype. The A. simplex larvae penetrated normal mucosa more frequently
      than atrophic area (p = 0.005). Finally, patients with normal mucosa infection
      were more likely to exhibit clinical symptoms than those with atrophic mucosa
      infection (odds ratio, 6.96; 95% confidence interval, 1.52-31.8). CONCLUSIONS: In
      Japan, A. simplex s.s. is the main etiological agent of human anisakiasis and
      tends to penetrate normal gastric mucosa. Careful endoscopic examination of
      normal gastric mucosa, particularly in the greater curvature of the stomach will
      improve the detection of Anisakis larvae.

PMID- 24586585
TI  - Influence of the sevoflurane concentration on the occurrence of epileptiform EEG
      patterns.
AB  - OBJECTIVES AND AIM: This study was performed to analyse the effects of different
      sevoflurane concentrations on the incidence of epileptiform EEG activity during
      induction of anaesthesia in children in the clinical routine. BACKGROUND: It was
      suggested in the literature to use sevoflurane concentrations lower than 8% to
      avoid epileptiform activity during induction of anaesthesia in children. METHODS:
      100 children (age: 4.6+/-3.0 years, ASA I-III, premedication with midazolam) were
      anaesthetized with 8% sevoflurane for 3 min or 6% sevoflurane for 5 min in 100%
      O2 via face mask followed by 4% sevoflurane until propofol and remifentanil were
      given for intubation. EEGs were recorded continuously and were analysed visually
      with regard to epileptiform EEG patterns. RESULTS: From start of sevoflurane
      until propofol/remifentanil administration, 38 patients (76%) with 8% sevoflurane
      had epileptiform EEG patterns compared to 26 patients (52%) with 6% (p = 0.0106).
      Epileptiform potentials tended to appear later in the course of the induction
      with 6% than with 8%. Up to an endtidal concentration of 6% sevoflurane, the
      number of children with epileptiform potentials was similar in both groups (p =
      0.3708). The cumulative number of children with epileptiform activity increased
      with increasing endtidal sevoflurane concentrations. The time from start of
      sevoflurane until loss of consciousness was similar in patients with 8% and 6%
      sevoflurane (42.2+/-17.5 s vs. 44.9 s +/-14.0 s; p = 0.4073). An EEG stage of
      deep anaesthesia with continuous delta waves <2.0 Hz appeared significantly
      earlier in the 8% than in the 6% group (64.0+/-22.2 s vs. 77.9+/-20.0 s, p =
      0.0022). CONCLUSION: The own analysis and data from the literature show that
      lower endtidal concentrations of sevoflurane and shorter administration times can
      be used to reduce epileptiform activity during induction of sevoflurane
      anaesthesia in children.

PMID- 24586584
TI  - Whole animal automated platform for drug discovery against multi-drug resistant
      Staphylococcus aureus.
AB  - Staphylococcus aureus, the leading cause of hospital-acquired infections in the
      United States, is also pathogenic to the model nematode Caenorhabditis elegans.
      The C. elegans-S. aureus infection model was previously carried out on solid agar
      plates where the bacteriovorous C. elegans feeds on a lawn of S. aureus. However,
      agar-based assays are not amenable to large scale screens for antibacterial
      compounds. We have developed a high throughput liquid screening assay that uses
      robotic instrumentation to dispense a precise amount of methicillin resistant S.
      aureus (MRSA) and worms in 384-well assay plates, followed by automated
      microscopy and image analysis. In validation of the liquid assay, an MRSA cell
      wall defective mutant, MW2DeltatarO, which is attenuated for killing in the agar
      based assay, was found to be less virulent in the liquid assay. This robust assay
      with a Z'-factor consistently greater than 0.5 was utilized to screen the Biomol
      4 compound library consisting of 640 small molecules with well characterized
      bioactivities. As proof of principle, 27 of the 30 clinically used antibiotics
      present in the library conferred increased C. elegans survival and were
      identified as hits in the screen. Surprisingly, the antihelminthic drug closantel
      was also identified as a hit in the screen. In further studies, we confirmed the
      anti-staphylococcal activity of closantel against vancomycin-resistant S. aureus
      isolates and other Gram-positive bacteria. The liquid C. elegans-S. aureus assay
      described here allows screening for anti-staphylococcal compounds that are not
      toxic to the host.

PMID- 24586586
TI  - Characterizing and modeling the dynamics of activity and popularity.
AB  - Social media, regarded as two-layer networks consisting of users and items, turn
      out to be the most important channels for access to massive information in the
      era of Web 2.0. The dynamics of human activity and item popularity is a crucial
      issue in social media networks. In this paper, by analyzing the growth of user
      activity and item popularity in four empirical social media networks, i.e.,
      Amazon, Flickr, Delicious and Wikipedia, it is found that cross links between
      users and items are more likely to be created by active users and to be acquired
      by popular items, where user activity and item popularity are measured by the
      number of cross links associated with users and items. This indicates that users
      generally trace popular items, overall. However, it is found that the inactive
      users more severely trace popular items than the active users. Inspired by
      empirical analysis, we propose an evolving model for such networks, in which the
      evolution is driven only by two-step random walk. Numerical experiments verified
      that the model can qualitatively reproduce the distributions of user activity and
      item popularity observed in empirical networks. These results might shed light on
      the understandings of micro dynamics of activity and popularity in social media
      networks. 

PMID- 24586587
TI  - Experience reverses the red effect among Chinese stockbrokers.
AB  - Recent research has shown that the color red influences psychological
      functioning. Red is hypothesized to be linked to aggression and danger in
      evolution, and these links are enhanced by culture-specific uses of red. Thus,
      color meanings are thought to be grounded in biologically based proclivities and
      learned associations. However, to date, there has been no direct evidence for the
      influence of experience on the red effect. This study focused on whether
      experience could change the psychological effects of the color red. In the
      context of the Chinese stock market, contrary to the meaning generally associated
      with red as negative and green as positive, red represents a rise in stock price
      and green stands for a decrease. An experiment using a 2*2 between subjects
      factorial design demonstrated that red (compared with green) impaired Chinese
      college students' performance on an IQ test (in accordance with the red effect),
      but the opposite effect was found among stockbrokers. These results provide
      direct evidence of learned color meanings, in support of the general model of
      color effect. 

PMID- 24586588
TI  - Lack of association of the caspase-12 long allele with community-acquired
      pneumonia in people of African descent.
AB  - Community-acquired pneumonia (CAP) is a common cause of sepsis. Active full
      length caspase-12 (CASP12L), confined to the people of African descent, has been
      associated with increased susceptibility to and mortality from severe sepsis. The
      objective of this study was to determine whether CASP12L was a marker for
      susceptibility and/or severity of CAP. We examined three CAP cohorts and two
      control populations: 241 adult Memphis African American CAP patients, 443
      pediatric African American CAP patients, 90 adult South African CAP patients, 120
      Memphis healthy adult African American controls and 405 adult Chicago African
      American controls. Clinical outcomes including mortality, acute respiratory
      distress syndrome (ARDS), septic shock or severe sepsis, need for mechanical
      ventilation, and S. pneumoniae bacteremia. Neither in the three individual CAP
      cohorts nor in the combined CAP cohorts, was mortality in CASP12L carriers
      significantly different from that in non-CASP12L carriers. No statistically
      significant association between genotype and any measures of CAP severity was
      found in any cohort. We conclude that the functional CASP12L allele is not a
      marker for susceptibility and/or severity of CAP. 

PMID- 24586589
TI  - Functional Fcgamma receptor polymorphisms are associated with human allergy.
AB  - OBJECTIVE: IgG Fc receptors (FcgammaRs) play important roles in immune responses.
      It is not clear whether FcgammaR receptors play a role in human asthma and
      allergy. The aim of current study was to investigate whether functional single
      nucleotide polymorphisms (SNPs) of FcgammaR genes (FCGR) are associated with
      human asthma and allergy. METHODS: Functional SNPs of FCGR2A (FcgammaRIIA
      131His>Arg, rs1801274), FCGR2B (FcgammaRIIB-187Ile>Thr, rs1050501), FCGR2C
      (FcgammaRIIC-13Gln>Stop, rs10917661), FCGR3A (FcgammaRIIIA-158Val>Phe, rs396991),
      and FCGR3B variants (FcgammaRIIIB NA1 and NA2) were genotyped in an asthma family
      cohort including 370 atopy positive, 239 atopy negative, and 169 asthma positive
      subjects. The genotype and phenotype data (asthma, bronchial hyper
      responsiveness, and atopy) of subjects were analyzed using family-based
      association tests (FBAT) and logistic regression adjusted for age and sex.
      RESULT: The FcgammaRIIA-131His>Arg SNP is significantly associated with atopy in
      a family-based association test (P = 0.00287) and in a logistic regression
      analysis (P = 0.0269, OR 0.732, 95% CI: 0.555-0.965). The FcgammaRIIA-131His (or
      rs1801274-A) allele capable of binding human IgG2 has a protective role against
      atopy. In addition, the rare FcgammaRIIB-187Thr (or rs1050501-C) allele defective
      for the receptor-mediated inhibitory signals is a risk factor for atopy (P =
      0.0031, OR 1.758, 95% CI: 1.209-2.556) and IgE production (P<0.001). However,
      variants of activating FcgammaRIIIA (rs396991), and FcgammaRIIIB (NA1 and NA2),
      and FcgammaRIIC (rs10917661) are not associated with asthma, BHR, and atopy
      (P>0.05). CONCLUSIONS: FcgammaRIIA and FcgammaRIIB functional polymorphisms may
      have a role in the pathogenesis of allergy.

PMID- 24586590
TI  - The core proteome and pan proteome of Salmonella Paratyphi A epidemic strains.
AB  - Comparative proteomics of the multiple strains within the same species can reveal
      the genetic variation and relationships among strains without the need to assess
      the genomic data. Similar to comparative genomics, core proteome and pan proteome
      can also be obtained within multiple strains under the same culture conditions.
      In this study we present the core proteome and pan proteome of four epidemic
      Salmonella Paratyphi A strains cultured under laboratory culture conditions. The
      proteomic information was obtained using a Two-dimensional gel electrophoresis (2
      DE) technique. The expression profiles of these strains were conservative,
      similar to the monomorphic genome of S. Paratyphi A. Few strain-specific proteins
      were found in these strains. Interestingly, non-core proteins were found in
      similar categories as core proteins. However, significant fluctuations in the
      abundance of some core proteins were also observed, suggesting that there is
      elaborate regulation of core proteins in the different strains even when they are
      cultured in the same environment. Therefore, core proteome and pan proteome
      analysis of the multiple strains can demonstrate the core pathways of metabolism
      of the species under specific culture conditions, and further the specific
      responses and adaptations of the strains to the growth environment. 

PMID- 24586591
TI  - Problem-based training improves recognition of patient hazards by advanced
      medical students during chart review: a randomized controlled crossover study.
AB  - BACKGROUND: Patient chart review is the gold standard for detection of potential
      patient hazards (i.e. medication errors or failure to follow up actionable
      results) in both routine clinical care and patient safety research. However,
      advanced medical students' ability to read patient charts and to identify patient
      hazards is rather poor. We therefore investigated whether it is possible to teach
      advanced medical students how to identify patient hazards independent of context
      (i.e. cancer versus cardiac failure) in patient charts. METHODS: All fifth-year
      medical students in one semester (n = 123) were randomized into two groups. One
      group (IC) received a patient chart review-training first and then a control
      intervention and the other group (CI) received the control-intervention first and
      then the patient chart review-training. Before and after the teaching sessions,
      students reviewed different scenarios with standardized fictional patient charts
      containing 12 common patient hazards. Two blinded raters rated the students'
      notes for any patient hazard addressed in the notes using a checklist. The
      students were blinded to the study question and design. There was no external
      funding and no harm for the participating students. RESULTS: A total of 35 data
      sets had to be excluded because of missing data. Overall, the students identified
      17% (IQR 8-29%) of the patient hazards before the training and 56% (IQR 41-66%)
      of the patient hazards after the training. At the second assessment students
      identified more patient hazards than at the first. They identified even more in
      the third. The effect was most pronounced after the patient chart review training
      (all p<.01). CONCLUSION: Patient chart review exercises and problem-based patient
      chart review training improve students' abilities to recognize patient hazards
      independent of context during patient chart review.

PMID- 24586592
TI  - The antidepressant trans-2-phenylcyclopropylamine protects mice from high-fat
      diet-induced obesity.
AB  - Mice treated with the antidepressant trans-2-phenylcyclopropylamine (2-PCPA) were
      protected against diet-induced-obesity, and adiposity was reversed in pre
      established diet-induced obese mice. Contrary to a recent report that inhibition
      of lysine-specific demethylase-1 by 2-PCPA results in increased energy
      expenditure, long-term 2-PCPA treatment had no such effect but its protection
      against obesity was associated with increased spontaneous locomotor activity,
      Moreover, pair feeding to assure equal caloric intake in wild type mice as well
      as in genetic hyperphagic mice (ob/ob) also resulted in weight reduction in 2
      PCPA treated mice that correlated with increased activity but no change in energy
      expenditure. Similarly, short-term intraperitoneal injections of 2-PCPA did not
      affect food intake but caused a substantial increase in locomotor activity in the
      light cycle that correlated with increased energy expenditure, whereas activity
      and energy expenditure were unchanged in the dark cycle. Lastly, 2-PCPA was also
      effective in reducing obesity in genetic UCP1 null mice. These data suggest that
      2-PCPA can reduce obesity by decreasing food intake in the long term while
      increasing activity in the short-term. However, the protective and weight loss
      effects of 2-PCPA are independent of UCP1-regulated thermogenesis or basal energy
      expenditure. 

PMID- 24586593
TI  - Atrial natriuretic peptide and type 2 diabetes development--biomarker and
      genotype association study.
AB  - BACKGROUND: We have recently shown that low plasma levels of mid-regional atrial
      natriuretic peptide (MR-ANP) predict development of diabetes and glucose
      progression over time, independently of known risk factors for diabetes
      development. However, since MR-ANP levels might be influenced by unknown factors
      causing diabetes, we cannot rule out that such relationship might be confounded.
      Previous studies have shown an association of a single nucleotide polymorphism
      rs5068 on the natriuretic peptide precursor A (NPPA) locus gene with higher
      levels of circulating ANP. Since gene variants are inherited randomly and not
      subject to confounding, we aimed to investigate whether the variant rs5068 within
      the NPPA locus is associated with incident type 2 diabetes. METHODS: We genotyped
      the variant rs5068 within the NPPA locus in 27,307 individuals without known
      diabetes from the Malmo Diet Cancer Study. Incident diabetes was retrieved
      through national and regional registers (median follow-up time of 14 years, 2,823
      incident diabetes cases). RESULTS: In Cox regression analysis adjusted for age,
      sex and BMI, we found that the carriers of at least one copy of the G allele of
      rs5068 had lower likelihood of incident diabetes within 14 years (HR = 0.88, 95%
      CI 0.78-0.99, p = 0.037). CONCLUSION: Our results indicate a role of the ANP
      system in the etiology of type 2 diabetes and might help provide insight in the
      metabolic actions of natriuretic peptides and the pathophysiology of type 2
      diabetes.

PMID- 24586594
TI  - The interaction effects of pri-let-7a-1 rs10739971 with PGC and ERCC6 gene
      polymorphisms in gastric cancer and atrophic gastritis.
AB  - BACKGROUND: The aim of this study was to investigate the interaction effects of
      pri-let-7a-1 rs10739971 with pepsinogen C (PGC) and excision repair cross
      complementing group 6 (ERCC6) gene polymorphisms and its association with the
      risks of gastric cancer and atrophic gastritis. We hoped to identify miRNA
      polymorphism or a combination of several polymorphisms that could serve as
      biomarkers for predicting the risk of gastric cancer and its precancerous
      diseases. METHODS: Sequenom MassARRAY platform method was used to detect
      polymorphisms of pri-let-7a-1 rs10739971 G -> A, PGC rs4711690 C -> G, PGC
      rs6458238 G -> A, PGC rs9471643 G -> C, and ERCC6 rs1917799 in 471 gastric cancer
      patients, 645 atrophic gastritis patients and 717 controls. RESULTS: An
      interaction effect of pri-let-7a-1 rs10739971 polymorphism with ERCC6 rs1917799
      polymorphism was observed for the risk of gastric cancer (P interaction = 0.026);
      and interaction effects of pri-let-7a-1 rs10739971 polymorphism with PGC
      rs6458238 polymorphism (P interaction = 0.012) and PGC rs9471643 polymorphism (P
      interaction = 0.039) were observed for the risk of atrophic gastritis.
      CONCLUSION: The combination of pri-let-7a-1 rs10739971 polymorphism and ERCC6 and
      PGC polymorphisms could provide a greater prediction potential than a single
      polymorphism on its own. Large-scale studies and molecular mechanism research are
      needed to confirm our findings.

PMID- 24586595
TI  - Predicting perioperative venous thromboembolism in Japanese gynecological
      patients.
AB  - OBJECTIVE: To develop a convenient screening method that can predict
      perioperative venous thromboembolism (VTE) and identify patients at risk of fatal
      perioperative pulmonary embolism (PE). METHODS: Patients hospitalized for
      gynecological abdominal surgery (n = 183) underwent hematology tests and
      multidetector computed tomography (MDCT) to detect VTE. All statistical analyses
      were carried out using the SPSS software program (PASWV19.0J). RESULTS: The
      following risk factors for VTE were identified by univariate analysis: plasmin
      alpha2-plasmin inhibitor complex (PIC), thrombin-antithrombin III complex (TAT),
      and prolonged immobility (all p<0.001); age, neoadjuvant chemotherapy (NAC),
      malignancy, hypertension, past history of VTE, and hormone therapy (all p<0.01);
      and hemoglobin, transverse tumor diameter, ovarian disease, and menopause (all
      p<0.05). Multivariate analysis using these factors revealed that PIC, age, and
      transverse tumor diameter were significant independent determinants of the risk
      of VTE. We then calculated the incidence rate of perioperative VTE using PIC and
      transverse tumor diameter in patient groups stratified by age. In patients aged
      <=40 years, PIC >=1.3 ug/mL and a transverse tumor diameter >=10 cm identified
      the high-risk group for VTE with an accuracy of 93.6%. For patients in their 50
      s, PIC >=1.3 ug/mL identified a high risk of VTE with an accuracy of 78.2%. In
      patients aged >=60 years, a transverse tumor diameter >=15 cm (irrespective of
      PIC) or PIC >=1.3 ug/mL identified the high-risk group with an accuracy of 82.4%.
      CONCLUSIONS: We propose new screening criteria for VTE risk that are based on
      PIC, transverse tumor diameter, and age. Our findings suggest the usefulness of
      these criteria for predicting the risk of perioperative VTE and for identifying
      patients with a high risk of fatal perioperative PE.

PMID- 24586596
TI  - Impact of phone call intervention on glycemic control in diabetes patients: a
      systematic review and meta-analysis of randomized, controlled trials.
AB  - BACKGROUND: Telephone-delivered intervention can provide many supports in
      diabetes self-management to improve glycemic control. Several trials showed that
      telephone intervention was positively associated with glycemic outcomes in
      diabetes. The objective of this meta-analysis was to assess the impact of
      telephone contact intervention (intervention group) on glycemic control compared
      with standard clinical care (control group). METHODS: Randomized control studies
      of telephone intervention in diabetes were searched on Medline (Pubmed), the
      Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and
      Allied Health Literature (CINAHL), Web of Science (ISI), and Scopus. Electronic
      search was done from inception to April 2013. The following MeSH terms were used:
      diabetes mellitus, randomized control trials and telemedicine, together with
      keywords including phone intervention, diabetes, and glycemic control. Historical
      search was also conducted on the references of relevant articles. The quality of
      the trials was assessed using Maastricht-Amsterdam scale. Treatment effect was
      estimated with mean difference in the change of hemoglobin A1c (HbA1c) from
      baseline between the intervention and control groups. RESULTS: A total of 203
      articles were examined. Five trials involving 953 patients met the inclusion
      criteria and contributed to the meta-analysis. Telephone contact intervention was
      no more effective than standard clinical care in improving glycemic control
      (pooled mean difference in HbA1c -0.38%, 95%CI -0.91 to 0.16%). CONCLUSIONS: This
      meta-analysis showed that the phone contact intervention was no more effective
      than standard clinical care in improving glycemic control in diabetes. However,
      telephone intervention may still have potential benefits especially for low-and
      middle-income countries; thus further large sample size and well-controlled
      studies are needed to evaluate the impact of the intervention.

PMID- 24586597
TI  - Decreased risk of stroke in patients with traumatic brain injury receiving
      acupuncture treatment: a population-based retrospective cohort study.
AB  - BACKGROUND: Patients with traumatic brain injury (TBI) face increased risk of
      stroke. Whether acupuncture can help to protect TBI patients from stroke has not
      previously been studied. METHODS: Taiwan's National Health Insurance Research
      Database was used to conduct a retrospective cohort study of 7409 TBI patients
      receiving acupuncture treatment and 29,636 propensity-score-matched TBI patients
      without acupuncture treatment in 2000-2008 as controls. Both TBI cohorts were
      followed until the end of 2010 and adjusted for immortal time to measure the
      incidence and adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) of
      new-onset stroke in the multivariable Cox proportional hazard models. RESULTS:
      TBI patients with acupuncture treatment (4.9 per 1000 person-years) had a lower
      incidence of stroke compared with those without acupuncture treatment (7.5 per
      1000 person-years), with a HR of 0.59 (95% CI = 0.50-0.69) after adjustment for
      sociodemographics, coexisting medical conditions and medications. The association
      between acupuncture treatment and stroke risk was investigated by sex and age
      group (20-44, 45-64, and >=65 years). The probability curve with log-rank test
      showed that TBI patients receiving acupuncture treatment had a lower probability
      of stroke than those without acupuncture treatment during the follow-up period
      (p<0.0001). CONCLUSION: Patients with TBI receiving acupuncture treatment show
      decreased risk of stroke compared with those without acupuncture treatment.
      However, this study was limited by lack of information regarding lifestyles,
      biochemical profiles, TBI severity, and acupuncture points used in treatments.

PMID- 24586598
TI  - An in vitro study on the effects of nisin on the antibacterial activities of 18
      antibiotics against Enterococcus faecalis.
AB  - Enterococcus faecalis rank among the leading causes of nosocomial infections
      worldwide and possesses both intrinsic and acquired resistance to a variety of
      antibiotics. Development of new antibiotics is limited, and pathogens continually
      generate new antibiotic resistance. Many researchers aim to identify strategies
      to effectively kill this drug-resistant pathogen. Here, we evaluated the effect
      of the antimicrobial peptide nisin on the antibacterial activities of 18
      antibiotics against E. faecalis. The MIC and MBC results showed that the
      antibacterial activities of 18 antibiotics against E. faecalis OG1RF, ATCC 29212,
      and strain E were significantly improved in the presence of 200 U/ml nisin.
      Statistically significant differences were observed between the results with and
      without 200 U/ml nisin at the same concentrations of penicillin or
      chloramphenicol (p<0.05). The checkerboard assay showed that the combination of
      nisin and penicillin or chloramphenicol had a synergetic effect against the three
      tested E. faecalis strains. The transmission electron microscope images showed
      that E. faecalis was not obviously destroyed by penicillin or chloramphenicol
      alone but was severely disrupted by either antibiotic in combination with nisin.
      Furthermore, assessing biofilms by a confocal laser scanning microscope showed
      that penicillin, ciprofloxacin, and chloramphenicol all showed stronger
      antibiofilm actions in combination with nisin than when these antibiotics were
      administered alone. Therefore, nisin can significantly improve the antibacterial
      and antibiofilm activities of many antibiotics, and certain antibiotics in
      combination with nisin have considerable potential for use as inhibitors of this
      drug-resistant pathogen. 

PMID- 24586599
TI  - Shale gas, wind and water: assessing the potential cumulative impacts of energy
      development on ecosystem services within the Marcellus play.
AB  - Global demand for energy has increased by more than 50 percent in the last half
      century, and a similar increase is projected by 2030. This demand will
      increasingly be met with alternative and unconventional energy sources.
      Development of these resources causes disturbances that strongly impact
      terrestrial and freshwater ecosystems. The Marcellus Shale gas play covers more
      than 160,934 km(2) in an area that provides drinking water for over 22 million
      people in several of the largest metropolitan areas in the United States (e.g.
      New York City, Washington DC, Philadelphia & Pittsburgh). Here we created
      probability surfaces representing development potential of wind and shale gas for
      portions of six states in the Central Appalachians. We used these predictions and
      published projections to model future energy build-out scenarios to quantify
      future potential impacts on surface drinking water. Our analysis predicts up to
      106,004 new wells and 10,798 new wind turbines resulting up to 535,023 ha of
      impervious surface (3% of the study area) and upwards of 447,134 ha of impacted
      forest (2% of the study area). In light of this new energy future, mitigating the
      impacts of energy development will be one of the major challenges in the coming
      decades. 

PMID- 24586600
TI  - Ant brood function as life preservers during floods.
AB  - Social organisms can surmount many ecological challenges by working collectively.
      An impressive example of such collective behavior occurs when ants physically
      link together into floating 'rafts' to escape from flooded habitat. However, raft
      formation may represent a social dilemma, with some positions posing greater
      individual risks than others. Here, we investigate the position and function of
      different colony members, and the costs and benefits of this functional geometry
      in rafts of the floodplain-dwelling ant Formica selysi. By causing groups of ants
      to raft in the laboratory, we observe that workers are distributed throughout the
      raft, queens are always in the center, and 100% of brood items are placed on the
      base. Through a series of experiments, we show that workers and brood are
      extremely resistant to submersion. Both workers and brood exhibit high survival
      rates after they have rafted, suggesting that occupying the base of the raft is
      not as costly as expected. The placement of all brood on the base of one cohesive
      raft confers several benefits: it preserves colony integrity, takes advantage of
      brood buoyancy, and increases the proportion of workers that immediately recover
      after rafting. 

PMID- 24586601
TI  - MCPerm: a Monte Carlo permutation method for accurately correcting the multiple
      testing in a meta-analysis of genetic association studies.
AB  - Traditional permutation (TradPerm) tests are usually considered the gold standard
      for multiple testing corrections. However, they can be difficult to complete for
      the meta-analyses of genetic association studies based on multiple single
      nucleotide polymorphism loci as they depend on individual-level genotype and
      phenotype data to perform random shuffles, which are not easy to obtain. Most
      meta-analyses have therefore been performed using summary statistics from
      previously published studies. To carry out a permutation using only genotype
      counts without changing the size of the TradPerm P-value, we developed a Monte
      Carlo permutation (MCPerm) method. First, for each study included in the meta
      analysis, we used a two-step hypergeometric distribution to generate a random
      number of genotypes in cases and controls. We then carried out a meta-analysis
      using these random genotype data. Finally, we obtained the corrected permutation
      P-value of the meta-analysis by repeating the entire process N times. We used
      five real datasets and five simulation datasets to evaluate the MCPerm method and
      our results showed the following: (1) MCPerm requires only the summary statistics
      of the genotype, without the need for individual-level data; (2) Genotype counts
      generated by our two-step hypergeometric distributions had the same distributions
      as genotype counts generated by shuffling; (3) MCPerm had almost exactly the same
      permutation P-values as TradPerm (r = 0.999; P<2.2e-16); (4) The calculation
      speed of MCPerm is much faster than that of TradPerm. In summary, MCPerm appears
      to be a viable alternative to TradPerm, and we have developed it as a freely
      available R package at CRAN: http://cran.r
      project.org/web/packages/MCPerm/index.html.

PMID- 24586602
TI  - Determinants of long-term care services among the elderly: a population-based
      study in Taiwan.
AB  - OBJECTIVES: The aim of the study was to investigate determinants of long-term
      care use and to clarify the differing characteristics of home/community-based and
      institution-based services users. DESIGN: Cross-sectional, population-based
      study. SETTING: Utilizing data from the 2005 National Health Interview Survey
      conducted in Taiwan. PARTICIPANTS: A national sample of 2,608 people (1,312 men,
      1,296 women) aged 65 and older. MEASUREMENTS: The utilization of long-term care
      services (both home/community- and institution-based services) was measured. A
      chi(2) analysis tested differences in baseline characteristics between
      home/community-based and institution-based long-term care users. The multiple
      logistic model was adopted with a hierarchical approach adding the Andersen
      model's predisposing, enabling, and need factors sequentially. Multiple logistic
      models further stratified data by gender and age. RESULTS: Compared with users of
      home/community-based care, those using institution-based care had less education
      (p = 0.019), greater likelihood of being single (p = 0.001), fewer family members
      (p = 0.002), higher prevalence of stool incontinence (p = 0.011) and dementia (P
      = .025), and greater disability (p = 0.016). After adjustment, age (compared with
      65-69 years; 75-79 years, odds ratio [OR] = 2.08, p = 0.044; age >=80, OR = 3.30,
      p = 0.002), being single (OR = 2.16, p = 0.006), urban living (OR = 1.68, p =
      0.037), stroke (OR = 2.08, p = 0.015), dementia (OR = 2.32, p = 0.007), 1-3 items
      of activities of daily living (ADL) disability (OR = 5.56, p<0.001), and 4-6
      items of ADL disability (OR = 21.57, p<0.001) were significantly associated with
      long-term care use. CONCLUSION: Age, single marital status, stroke, dementia, and
      ADL disability are predictive factors for long-term care use. The utilization was
      directly proportional to the level of disability.

PMID- 24586604
TI  - Sea ice biogeochemistry: a guide for modellers.
AB  - Sea ice is a fundamental component of the climate system and plays a key role in
      polar trophic food webs. Nonetheless sea ice biogeochemical dynamics at large
      temporal and spatial scales are still rarely described. Numerical models may
      potentially contribute integrating among sparse observations, but available
      models of sea ice biogeochemistry are still scarce, whether their relevance for
      properly describing the current and future state of the polar oceans has been
      recently addressed. A general methodology to develop a sea ice biogeochemical
      model is presented, deriving it from an existing validated model application by
      extension of generic pelagic biogeochemistry model parameterizations. The
      described methodology is flexible and considers different levels of ecosystem
      complexity and vertical representation, while adopting a strategy of coupling
      that ensures mass conservation. We show how to apply this methodology step by
      step by building an intermediate complexity model from a published realistic
      application and applying it to analyze theoretically a typical season of first
      year sea ice in the Arctic, the one currently needing the most urgent
      understanding. The aim is to (1) introduce sea ice biogeochemistry and address
      its relevance to ocean modelers of polar regions, supporting them in adding a new
      sea ice component to their modelling framework for a more adequate representation
      of the sea ice-covered ocean ecosystem as a whole, and (2) extend our knowledge
      on the relevant controlling factors of sea ice algal production, showing that
      beyond the light and nutrient availability, the duration of the sea ice season
      may play a key-role shaping the algal production during the on going and upcoming
      projected changes. 

PMID- 24586603
TI  - Cognitive and affective changes in mild to moderate Alzheimer's disease patients
      undergoing switch of cholinesterase inhibitors: a 6-month observational study.
AB  - Patients with Alzheimer's disease after an initial response to cholinesterase
      inhibitors may complain a later lack of efficacy. This, in association with
      incident neuropsychiatric symptoms, may worsen patient quality of life. Thus, the
      switch to another cholinesterase inhibitor could represent a valid therapeutic
      strategy. The aim of this study was to investigate the effectiveness of the
      switch from one to another cholinesterase inhibitor on cognitive and affective
      symptoms in mild to moderate Alzheimer disease patients. Four hundred twenty
      three subjects were included from the EVOLUTION study, an observational,
      longitudinal, multicentre study conducted on Alzheimer disease patients who
      switched to different cholinesterase inhibitor due either to lack/loss of
      efficacy or response, reduced tolerability or poor compliance. All patients
      underwent cognitive and neuropsychiatric assessments, carried out before the
      switch (baseline), and at 3 and 6-month follow-up. A significant effect of the
      different switch types was found on Mini-Mental State Examination score during
      time, with best effectiveness on mild Alzheimer's disease patients switching from
      oral cholinesterase inhibitors to rivastigmine patch. Depressive symptoms, when
      measured using continuous Neuropsychiatric Inventory values, decreased
      significantly, while apathy symptoms remained stable over the 6 months after the
      switch. However, frequency of both depression and apathy, when measured
      categorically using Neuropsychiatric Inventory cut-off scores, did not change
      significantly during time. In mild to moderate Alzheimer disease patients with
      loss of efficacy and tolerability during cholinesterase inhibitor treatment, the
      switch to another cholinesterase inhibitor may represent an important option for
      slowing cognitive deterioration. The evidence of apathy stabilization and the
      positive tendency of depressive symptom improvement should definitively be
      confirmed in double-blind controlled studies. 

PMID- 24586605
TI  - BRAF-V600 mutations have no prognostic impact in stage IV melanoma patients
      treated with monochemotherapy.
AB  - BACKGROUND: The impact of BRAF tumor mutations on the natural course of disease
      of melanoma patients is controversial. PATIENTS AND METHODS: We analyzed the
      mutational status and overall survival of 215 patients receiving treatment with
      dacarbazine or temozolomide. All patients who started first-line treatment at our
      institution between 2000 and 2010 were included to prevent selection and bias due
      to thereafter arising therapeutic options. RESULTS: No patient received BRAF- or
      MEK-inhibitors during follow-up. Survival was associated with the pattern of
      visceral involvement, the presence of brain metastases and the serum lactate
      dehydrogenase level (all p<0.001). The BRAF-V600 mutational status was not
      associated with survival and no differences in overall survival were detected
      according to age, gender or to the cytotoxic agent used for therapy. In Cox
      regression analysis the presence of brain metastases (hazard ratio 2.3; p<0.001)
      and an elevated serum LDH (hazard ratio 2.5; p<0.001) were the only factors,
      which independently predicted survival. CONCLUSIONS: No differences in prognosis
      were observed according to the BRAF mutational status in patients with distant
      metastasis treated with monochemotherapy.

PMID- 24586606
TI  - Over-expressed Testis-specific Protein Y-encoded 1 as a novel biomarker for male
      hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is a male-predominant cancer. Previous studies
      have focused on the sex-related disparity in HCC, but the underlying mechanism
      remains unclear. Here, we aimed to discover characteristic biomarkers for male
      HCC. Clinical samples were subjected to iTRAQ labeling followed by 2DLC-ESI-MS/MS
      analysis. Seventy-three differential proteins containing 16 up-regulated and 57
      down-regulated proteins were screened out in the male HCC group compared to that
      in female HCC group. Testis-specific Protein Y-encoded 1(TSPY1) is
      characteristically present in male HCC and was chosen for further investigation.
      The data from the functional effects of TSPY1 indicated that over-expression of
      TSPY1 could potentiate HCC cell proliferation, increase soft agar colonization,
      induce higher cell invasive ability and correlate with the metastatic potential
      of the HCC cell lines. In addition, TSPY1 and androgen receptor (AR) were co
      expressed simultaneously in HCC cell lines as well as in HCC tissue. TSPY1 up- or
      down-regulation could lead to a high or low level expression of AR. These results
      implied that TSPY1 may be included in the regulation of AR expression involved in
      male HCC and it may act as a novel biomarker for male HCC. 

PMID- 24586607
TI  - Measuring and valuing health-related quality of life among children and
      adolescents in mainland China--a pilot study.
AB  - BACKGROUND: The Child Health Utility 9D (CHU9D), a new generic preference-based
      health-related quality of life (HRQoL) instrument, has been validated for use in
      young people in both the UK and Australia. The main objectives of this study were
      to examine the feasibility of using a Chinese version of the CHU9D (CHU9D-CHN) to
      assess HRQoL and to investigate the association of physical activity, homework
      hours and sleep duration with HRQoL in children and adolescents in Mainland
      China. METHODS: Data were collected using a multi-stage sampling method from
      grades 4-12 students in May 2013 in Nanjing, China. Consenting participants (N =
      815) completed a self-administered questionnaire including the CHU9D-CHN
      instrument and information on physical activity, homework and sleep duration,
      self-reported health status, and socio-demographic characteristics. Descriptive
      and multivariate linear regression analyses were undertaken. CHU9D-CHN utility
      scores were generated by employing two scoring algorithms currently available for
      the instrument, the first derived from UK adults utilising the standard gamble
      (SG) valuation method and the second derived from Australian adolescents
      utilising the best-worst scaling (BWS) method. RESULTS: It was found that CHU9D
      utility scores discriminated well in relation to self-reported health status and
      that better health status was significantly associated with higher utility scores
      regardless of which scoring algorithm was employed (both p<0.001). The adjusted
      mean utilities were significantly higher for physically active than inactive
      students (0.023 by SG, 0.029 by BWS scoring methods, p<0.05). An additional hour
      of doing homework and sleep duration were, separately, associated with mean
      utilities of -0.019 and 0.032 based on SG, and -0.021 and 0.040 according to BWS
      scoring algorithms (p<0.01). CONCLUSION: The CHU9D-CHN shows promise for
      measuring and valuing the HRQoL of children and adolescents in China. Levels of
      self-reported physical activity, homework and sleep time were important
      influencers of utility scores.

PMID- 24586608
TI  - Elevated expression of miR-210 predicts poor survival of cancer patients: a
      systematic review and meta-analysis.
AB  - BACKGROUND: MiRNAs are important regulators of different biological processes,
      including tumorigenesis. MiR-210 is a potential prognostic factor for survival in
      patients with cancer according to previous clinical researches. We conducted a
      systematic review and meta-analysis to summarize the significance of increased
      miR-210 expression in the prognosis of indicated cancers. METHODOLOGY/PRINCIPAL
      FINDINGS: The present systematic review and meta-analysis of 16 researches
      included 1809 patients with 7 different types of cancers from 7 countries, and
      aimed to explore the association between miR-210 expression and the survival of
      cancer patients. Over-expression of miR-210 may predict poor overall survival
      (OS, HR = 1.33, 95% CI: 0.85-2.09, P = 0.210), but the effect was not
      significant. While the predictive effect on disease-free survival (DFS, HR =
      1.89, 95% CI: 1.30-2.74, P = 0.001), progression-free survival (PFS, HR = 1.20,
      95% CI: 1.05-1.38, P = 0.007) and relapse-free survival(RFS, HR = 4.42, 95% CI:
      2.14-9.15, P = 0.000) for patients with breast cancer, primary head and neck
      squamous cell carcinoma (HNSCC), renal cancer, soft-tissue sarcoma, pediatric
      osteosarcoma, bladder cancer or glioblastoma was certain. Subgroup analysis
      showed the limited predictive effect of over-expressed miR-210 on breast cancer
      OS (HR = 1.63, 95% CI: 0.47-5.67, P = 0.443), breast cancer DFS (HR = 2.03, 95%
      CI: 0.90-4.57, P = 0.088), sarcoma OS (HR = 1.24, 95% CI: 0.20-7.89, P = 0.818)
      and renal cancer OS (HR = 1.16, 95% CI: 0.27-4.94, P = 0.842).
      CONCLUSIONS/SIGNIFICANCE: This systematic review and meta-analysis suggests that
      miR-210 has a predictive effect on survival of patients with studied cancer types
      as indexed by disease-free survival, progression-free survival and relapse-free
      survival. While the predictive effect on overall survival, breast cancer overall
      survival, breast cancer disease-free survival, sarcoma overall survival and renal
      cancer overall survival was not statistically significant.

PMID- 24586609
TI  - The effect of virtual endoscopy simulator training on novices: a systematic
      review.
AB  - BACKGROUND: Advances in virtual endoscopy simulators have paralleled an interest
      in medical simulation for gastrointestinal endoscopy training. OBJECTIVE: The
      primary objective was to determine whether the virtual endoscopy simulator
      training could improve the performance of novices. DESIGN: A systematic review.
      SETTING: Randomized controlled trials (RCTs) that compared virtual endoscopy
      simulator training with bedside teaching or any other intervention for novices
      were collected. PATIENTS: Novice endoscopists. INTERVENTIONS: The PRISMA
      statement was followed during the course of the research. The Cochrane Central
      Register of Controlled Trials, MEDLINE, EMBASE, and ScienceDirect were searched
      (up to July 2013). Data extraction and assessment were independently performed.
      MAIN OUTCOME MEASUREMENTS: Independent procedure completion, total procedure time
      and required assistance. RESULTS: Fifteen studies (n = 354) were eligible for
      inclusion: 9 studies designed for colonoscopy training, 6 for gastroscopy
      training. For gastroscopy training, procedure completed independently was
      reported in 87.7% of participants in simulator training group compared to 70.0%
      of participants in control group (1 study; 22 participants; RR 1.25; 95% CI 1.13
      1.39; P<0.0001). For colonoscopy training, procedure completed independently was
      reported in 89.3% of participants in simulator training group compared to 88.9%
      of participants in control group (7 study; 163 participants; RR 1.10; 95% CI 0.88
      1.37; P = 0.41; I(2) = 85%). LIMITATIONS: The included studies are quite in
      homogeneous with respect to training schedule and procedure. CONCLUSIONS: Virtual
      endoscopy simulator training might be effective for gastroscopy, but so far no
      data is available to support this for colonoscopy.

PMID- 24586610
TI  - Non-Gaussian diffusion imaging for enhanced contrast of brain tissue affected by
      ischemic stroke.
AB  - Recent diffusion MRI studies of stroke in humans and animals have shown that the
      quantitative parameters characterising the degree of non-Gaussianity of the
      diffusion process are much more sensitive to ischemic changes than the apparent
      diffusion coefficient (ADC) considered so far as the "gold standard". The
      observed changes exceeded that of the ADC by a remarkable factor of 2 to 3. These
      studies were based on the novel non-Gaussian methods, such as diffusion kurtosis
      imaging (DKI) and log-normal distribution function imaging (LNDFI). As shown in
      our previous work investigating the animal stroke model, a combined analysis
      using two methods, DKI and LNDFI provides valuable complimentary information. In
      the present work, we report the application of three non-Gaussian diffusion
      models to quantify the deviations from the Gaussian behaviour in stroke induced
      by transient middle cerebral artery occlusion in rat brains: the gamma
      distribution function (GDF), the stretched exponential model (SEM), and the
      biexponential model. The main goal was to compare the sensitivity of various non
      Gaussian metrics to ischemic changes and to investigate if a combined application
      of several models will provide added value in the assessment of stroke. We have
      shown that two models, GDF and SEM, exhibit a better performance than the
      conventional method and allow for a significantly enhanced visualization of
      lesions. Furthermore, we showed that valuable information regarding spatial
      properties of stroke lesions can be obtained. In particular, we observed a
      stratified cortex structure in the lesions that were well visible in the maps of
      the GDF and SEM metrics, but poorly distinguishable in the ADC-maps. Our results
      provided evidence that cortical layers tend to be differently affected by
      ischemic processes. 

PMID- 24586611
TI  - Transcription factor binding sites prediction based on modified nucleosomes.
AB  - In computational methods, position weight matrices (PWMs) are commonly applied
      for transcription factor binding site (TFBS) prediction. Although these matrices
      are more accurate than simple consensus sequences to predict actual binding
      sites, they usually produce a large number of false positive (FP) predictions and
      so are impoverished sources of information. Several studies have employed
      additional sources of information such as sequence conservation or the vicinity
      to transcription start sites to distinguish true binding regions from random
      ones. Recently, the spatial distribution of modified nucleosomes has been shown
      to be associated with different promoter architectures. These aligned patterns
      can facilitate DNA accessibility for transcription factors. We hypothesize that
      using data from these aligned and periodic patterns can improve the performance
      of binding region prediction. In this study, we propose two effective features,
      "modified nucleosomes neighboring" and "modified nucleosomes occupancy", to
      decrease FP in binding site discovery. Based on these features, we designed a
      logistic regression classifier which estimates the probability of a region as a
      TFBS. Our model learned each feature based on Sp1 binding sites on Chromosome 1
      and was tested on the other chromosomes in human CD4+T cells. In this work, we
      investigated 21 histone modifications and found that only 8 out of 21 marks are
      strongly correlated with transcription factor binding regions. To prove that
      these features are not specific to Sp1, we combined the logistic regression
      classifier with the PWM, and created a new model to search TFBSs on the genome.
      We tested the model using transcription factors MAZ, PU.1 and ELF1 and compared
      the results to those using only the PWM. The results show that our model can
      predict Transcription factor binding regions more successfully. The relative
      simplicity of the model and capability of integrating other features make it a
      superior method for TFBS prediction. 

PMID- 24586612
TI  - Periadventitial application of rapamycin-loaded nanoparticles produces sustained
      inhibition of vascular restenosis.
AB  - Open vascular reconstructions frequently fail due to the development of recurrent
      disease or intimal hyperplasia (IH). This paper reports a novel drug delivery
      method using a rapamycin-loaded poly(lactide-co-glycolide) (PLGA) nanoparticles
      (NPs)/pluronic gel system that can be applied periadventitially around the
      carotid artery immediately following the open surgery. In vitro studies revealed
      that rapamycin dispersed in pluronic gel was rapidly released over 3 days whereas
      release of rapamycin from rapamycin-loaded PLGA NPs embedded in pluronic gel was
      more gradual over 4 weeks. In cultured rat vascular smooth muscle cells (SMCs),
      rapamycin-loaded NPs produced durable (14 days versus 3 days for free rapamycin)
      inhibition of phosphorylation of S6 kinase (S6K1), a downstream target in the
      mTOR pathway. In a rat balloon injury model, periadventitial delivery of
      rapamycin-loaded NPs produced inhibition of phospho-S6K1 14 days after balloon
      injury. Immunostaining revealed that rapamycin-loaded NPs reduced SMC
      proliferation at both 14 and 28 days whereas rapamycin alone suppressed
      proliferation at day 14 only. Moreover, rapamycin-loaded NPs sustainably
      suppressed IH for at least 28 days following treatment, whereas rapamycin alone
      produced suppression on day 14 with rebound of IH by day 28. Since rapamycin,
      PLGA, and pluronic gel have all been approved by the FDA for other human
      therapies, this drug delivery method could potentially be translated into human
      use quickly to prevent failure of open vascular reconstructions. 

PMID- 24586613
TI  - Inhibition of post-transcriptional RNA processing by CDK inhibitors and its
      implication in anti-viral therapy.
AB  - Cyclin-dependent kinases (CDKs) are key regulators of the cell cycle and RNA
      polymerase II mediated transcription. Several pharmacological CDK inhibitors are
      currently in clinical trials as potential cancer therapeutics and some of them
      also exhibit antiviral effects. Olomoucine II and roscovitine, purine-based
      inhibitors of CDKs, were described as effective antiviral agents that inhibit
      replication of a broad range of wild type human viruses. Olomoucine II and
      roscovitine show high selectivity for CDK7 and CDK9, with important functions in
      the regulation of RNA polymerase II transcription. RNA polymerase II is necessary
      for viral transcription and following replication in cells. We analyzed the
      effect of inhibition of CDKs by olomoucine II on gene expression from viral
      promoters and compared its effect to widely-used roscovitine. We found that both
      roscovitine and olomoucine II blocked the phosphorylation of RNA polymerase II C
      terminal domain. However the repression of genes regulated by viral promoters was
      strongly dependent on gene localization. Both roscovitine and olomoucine II
      inhibited expression only when the viral promoter was not integrated into
      chromosomal DNA. In contrast, treatment of cells with genome-integrated viral
      promoters increased their expression even though there was decreased
      phosphorylation of the C-terminal domain of RNA polymerase II. To define the
      mechanism responsible for decreased gene expression after pharmacological CDK
      inhibitor treatment, the level of mRNA transcription from extrachromosomal DNA
      was determined. Interestingly, our results showed that inhibition of RNA
      polymerase II C-terminal domain phosphorylation increased the number of
      transcribed mRNAs. However, some of these mRNAs were truncated and lacked
      polyadenylation, which resulted in decreased translation. These results suggest
      that phosphorylation of RNA polymerase II C-terminal domain is critical for
      linking transcription and posttrancriptional processing of mRNA expressed from
      extrachromosomal DNA. 

PMID- 24586614
TI  - Central proliferation and neurogenesis is impaired in type 2 diabetes and
      prediabetes animal models.
AB  - Type 2 diabetes (T2D) is an important risk factor to suffer dementia, including
      Alzheimer's disease (AD), and some neuropathological features observed in
      dementia could be mediated by T2D metabolic alterations. Since brain atrophy and
      impaired neurogenesis have been observed both T2D and AD we analyzed central
      nervous system (CNS) morphological alterations in the db/db mice (leptin receptor
      KO mice), as a model of long-term insulin resistance and T2D, and in C57Bl6 mice
      fed with high fat diet (HFD), as a model of diet induced insulin resistance and
      prediabetes. Db/db mice showed an age-dependent cortical and hippocampal atrophy,
      whereas in HFD mice cortex and hippocampus were preserved. We also detected
      increased neurogenesis and cell proliferation rates in young db/db mice when
      compared with control littermates. Our study shows that metabolic parameters
      serve as predictors of both atrophy and altered proliferation and neurogenesis in
      the CNS. Moreover in the cortex, atrophy, cell proliferation and neurogenesis
      were significantly correlated. Our data suggest that T2D may underline some of
      the pathological features observed in the dementia process. They also support
      that blood glucose control in elderly patients could help to slow down dementia
      evolution and maybe, improve its prognosis. 

PMID- 24586615
TI  - Serum 1H-NMR metabolomic fingerprints of acute-on-chronic liver failure in
      intensive care unit patients with alcoholic cirrhosis.
AB  - INTRODUCTION: Acute-on-chronic liver failure is characterized by acute
      deterioration of liver function in patients with compensated or decompensated,
      but stable, cirrhosis. However, there is no accurate definition of acute-on
      chronic liver failure and physicians often use this term to describe different
      clinical entities. Metabolomics investigates metabolic changes in biological
      systems and identifies the biomarkers or metabolic profiles. Our study assessed
      the metabolomic profile of serum using proton nuclear magnetic resonance ((1)H
      NMR) spectroscopy to identify metabolic changes related to acute-on-chronic liver
      failure. PATIENTS: Ninety-three patients with compensated or decompensated
      cirrhosis (CLF group) but stable liver function and 30 patients with cirrhosis
      and hospitalized for the management of an acute event who may be responsible of
      acute-on-chronic liver failure (ACLF group), were fully analyzed. Blood samples
      were drawn at admission, and sera were separated and stored at -80 degrees C
      until (1)H-NMR spectral analysis. Using orthogonal projection to latent-structure
      discriminant analyses, various metabolites contribute to the complete separation
      between these both groups. RESULTS: The predictability of the model was 0.73
      (Q(2) Y) and the explained variance was 0.63 (R(2) Y). The main metabolites that
      had increased signals related to acute-on-chronic liver failure were lactate,
      pyruvate, ketone bodies, glutamine, phenylalanine, tyrosine, and creatinine. High
      density lipids were lower in the ALCF group than in CLF group. CONCLUSION: A
      serum metabolite fingerprint for acute-on-chronic liver failure, obtained with
      (1)H-NMR, was identified. Metabolomic profiling may aid clinical evaluation of
      patients with cirrhosis admitted into intensive care units with acute-on-chronic
      liver failure, and provide new insights into the metabolic processes involved in
      acute impairment of hepatic function.

PMID- 24586616
TI  - Transportation network with fluctuating input/output designed by the bio-inspired
      Physarum algorithm.
AB  - In this paper, we propose designing transportation network topology and traffic
      distribution under fluctuating conditions using a bio-inspired algorithm. The
      algorithm is inspired by the adaptive behavior observed in an amoeba-like
      organism, plasmodial slime mold, more formally known as plasmodium of Physarum
      plycephalum. This organism forms a transportation network to distribute its
      protoplasm, the fluidic contents of its cell, throughout its large cell body. In
      this process, the diameter of the transportation tubes adapts to the flux of the
      protoplasm. The Physarum algorithm, which mimics this adaptive behavior, has been
      widely applied to complex problems, such as maze solving and designing the
      topology of railroad grids, under static conditions. However, in most situations,
      environmental conditions fluctuate; for example, in power grids, the consumption
      of electric power shows daily, weekly, and annual periodicity depending on the
      lifestyles or the business needs of the individual consumers. This paper studies
      the design of network topology and traffic distribution with oscillatory input
      and output traffic flows. The network topology proposed by the Physarum algorithm
      is controlled by a parameter of the adaptation process of the tubes. We observe
      various rich topologies such as complete mesh, partial mesh, Y-shaped, and V
      shaped networks depending on this adaptation parameter and evaluate them on the
      basis of three performance functions: loss, cost, and vulnerability. Our results
      indicate that consideration of the oscillatory conditions and the phase-lags in
      the multiple outputs of the network is important: The building and/or maintenance
      cost of the network can be reduced by introducing the oscillating condition, and
      when the phase-lag among the outputs is large, the transportation loss can also
      be reduced. We use stability analysis to reveal how the system exhibits various
      topologies depending on the parameter. 

PMID- 24586617
TI  - The redox function of APE1 is involved in the differentiation process of stem
      cells toward a neuronal cell fate.
AB  - Low-to-moderate levels of reactive oxygen species (ROS) govern different steps of
      neurogenesis via molecular pathways that have been decrypted only partially.
      Although it has been postulated that redox-sensitive molecules are involved in
      neuronal differentiation, the molecular bases for this process have not been
      elucidated yet. The aim of this work was therefore to study the role played by
      the redox-sensitive, multifunctional protein APE1/Ref-1 (APE1) in the
      differentiation process of human adipose tissue-derived multipotent adult stem
      cells (hAT-MASC) and embryonic carcinoma stem cells (EC) towards a neuronal
      phenotype. METHODS AND RESULTS: Applying a definite protocol, hAT-MASC can adopt
      a neural fate. During this maturation process, differentiating cells
      significantly increase their intracellular Reactive Oxygen Species (ROS) levels
      and increase the APE1 nuclear fraction bound to chromatin. This latter event is
      paralleled by the increase of nuclear NF-kappaB, a transcription factor regulated
      by APE1 in a redox-dependent fashion. Importantly, the addition of the
      antioxidant N-acetyl cysteine (NAC) to the differentiation medium partially
      prevents the nuclear accumulation of APE1, increasing the neuronal
      differentiation of hAT-MASC. To investigate the involvement of APE1 in the
      differentiation process, we employed E3330, a specific inhibitor of the APE1
      redox function. The addition of E3330, either to the neurogenic embryonic
      carcinoma cell line NT2-D1or to hAT-MASC, increases the differentiation of stem
      cells towards a neural phenotype, biasing the differentiation towards specific
      subtypes, such as dopaminergic cells. In conclusion, during the differentiation
      process of stem cells towards a neuroectodermic phenotype, APE1 is recruited, in
      a ROS-dependent manner, to the chromatin. This event is associated with an
      inhibitory effect of APE1 on neurogenesis that may be reversed by E3330.
      Therefore, E3330 may be employed both to boost neural differentiation and to bias
      the differentiation potential of stem cells towards specific neuronal subtypes.
      These findings provide a molecular basis for the redox-mediated hypothesis of
      neuronal differentiation program.

PMID- 24586618
TI  - Dissecting the molecular mechanism of ionizing radiation-induced tissue damage in
      the feather follicle.
AB  - Ionizing radiation (IR) is a common therapeutic agent in cancer therapy. It
      damages normal tissue and causes side effects including dermatitis and mucositis.
      Here we use the feather follicle as a model to investigate the mechanism of IR
      induced tissue damage, because any perturbation of feather growth will be clearly
      recorded in its regular yet complex morphology. We find that IR induces defects
      in feather formation in a dose-dependent manner. No abnormality was observed at 5
      Gy. A transient, reversible perturbation of feather growth was induced at 10 Gy,
      leading to defects in the feather structure. This perturbation became
      irreversible at 20 Gy. Molecular and cellular analysis revealed P53 activation,
      DNA damage and repair, cell cycle arrest and apoptosis in the pathobiology. IR
      also induces patterning defects in feather formation, with disrupted branching
      morphogenesis. This perturbation is mediated by cytokine production and Stat1
      activation, as manipulation of cytokine levels or ectopic Stat1 over-expression
      also led to irregular feather branching. Furthermore, AG-490, a chemical
      inhibitor of Stat1 signaling, can partially rescue IR-induced tissue damage. Our
      results suggest that the feather follicle could serve as a useful model to
      address the in vivo impact of the many mechanisms of IR-induced tissue damage. 

PMID- 24586619
TI  - Whole genome analysis of a community-associated methicillin-resistant
      Staphylococcus aureus ST59 isolate from a case of human sepsis and severe
      pneumonia in China.
AB  - We report a case of necrotizing pneumonia in a young patient caused by community
      acquired-methicillin resistant Staphylococcus aureus (CA-MRSA) in a teaching
      hospital in the People's Republic of China. The patient had a typical clinical
      presentation and was successfully treated with antibiotics and intravenous
      immunoglobulin. A CA-MRSA strain, named SA268, was isolated from the blood of the
      patient. The isolate was susceptible to most antimicrobial agents, except
      cephalosporins, penicillins, and beta-lactamase inhibitor combinations. Multi
      locus sequence typing (MLST) assigned SA268 to ST59, a clone widely spread in
      eastern Asia. The strain was positive for Panton Valentine Leukocidin (PVL)
      encoding genes and SCCmec type V. We sequenced the complete genome of the SA268
      isolate. The genome of SA268 was almost identical to that of the Taiwanese ST59
      CA-MRSA strains M013 and SA957. However, we observed several differences in gene
      composition, which included differences in the SCCmec element and several
      lipoprotein genes that were present in the Taiwanese strains but absent from
      SA268. 

PMID- 24586620
TI  - IL-10-producing B cells are induced early in HIV-1 infection and suppress HIV-1
      specific T cell responses.
AB  - A rare subset of IL-10-producing B cells, named regulatory B cells (Bregs),
      suppresses adaptive immune responses and inflammation in mice. In this study, we
      examined the role of IL-10-producing B cells in HIV-1 infection. Compared to
      uninfected controls, IL-10-producing B cell frequencies were elevated in both
      blood and sigmoid colon during the early and chronic phase of untreated HIV-1
      infection. Ex vivo IL-10-producing B cell frequency in early HIV-1 infection
      directly correlated with viral load. IL-10-producing B cells from HIV-1 infected
      individuals were enriched in CD19(+)TIM-1(+) B cells and were enriched for
      specificity to trimeric HIV-1 envelope protein. Anti-retroviral therapy was
      associated with reduced IL-10-producing B cell frequencies. Treatment of B cells
      from healthy donors with microbial metabolites and Toll-like receptor (TLR)
      agonists could induce an IL-10 producing phenotype, suggesting that the elevated
      bacterial translocation characteristic of HIV-1 infection may promote IL-10
      producing B cell development. Similar to regulatory B cells found in mice, IL-10
      producing B cells from HIV-1-infected individuals suppressed HIV-1-specific T
      cell responses in vitro, and this suppression is IL-10-dependent. Also, ex vivo
      IL-10-producing B cell frequency inversely correlated with contemporaneous ex
      vivo HIV-1-specific T cell responses. Our findings show that IL-10-producing B
      cells are induced early in HIV-1 infection, can be HIV-1 specific, and are able
      to inhibit effective anti-HIV-1 T cell responses. HIV-1 may dysregulate B cells
      toward Bregs as an immune evasion strategy. 

PMID- 24586621
TI  - Assessment of RT-qPCR normalization strategies for accurate quantification of
      extracellular microRNAs in murine serum.
AB  - Extracellular microRNAs (miRNAs) are under investigation as minimally-invasive
      biomarkers for a wide range of disease conditions. We have recently shown in a
      mouse model of the progressive muscle-wasting condition Duchenne muscular
      dystrophy (DMD) that a set of highly elevated serum miRNAs reflects the
      regenerative status of muscle. These miRNAs are promising biomarkers for
      monitoring DMD disease progression and the response to experimental therapies.
      The gold standard miRNA detection methodology is Reverse Transcriptase
      quantitative Polymerase Chain Reaction (RT-qPCR), which typically exhibits high
      sensitivity and wide dynamic range. Accurate determination of miRNA levels is
      affected by RT-qPCR normalization method and therefore selection of the optimal
      strategy is of critical importance. Serum miRNA abundance was measured by RT-qPCR
      array in 14 week old mice, and by individual RT-qPCR assays in a time course
      experiment spanning 48 weeks. Here we utilize these two datasets to assess the
      validity of three miRNA normalization strategies (a) normalization to the average
      of all Cq values from array experiments, (b) normalization to a stably expressed
      endogenous reference miRNA, and (c) normalization to an external spike-in
      synthetic oligonucleotide. Normalization approaches based on endogenous control
      miRNAs result in an under-estimation of miRNA levels by a factor of ~2. An
      increase in total RNA and total miRNA was observed in dystrophic serum which may
      account for this systematic bias. We conclude that the optimal strategy for this
      model system is to normalize to a synthetic spike-in control oligonucleotide. 

PMID- 24586622
TI  - Integration of 3D structure from disparity into biological motion perception
      independent of depth awareness.
AB  - Images projected onto the retinas of our two eyes come from slightly different
      directions in the real world, constituting binocular disparity that serves as an
      important source for depth perception - the ability to see the world in three
      dimensions. It remains unclear whether the integration of disparity cues into
      visual perception depends on the conscious representation of stereoscopic depth.
      Here we report evidence that, even without inducing discernible perceptual
      representations, the disparity-defined depth information could still modulate the
      visual processing of 3D objects in depth-irrelevant aspects. Specifically,
      observers who could not discriminate disparity-defined in-depth facing
      orientations of biological motions (i.e., approaching vs. receding) due to an
      excessive perceptual bias nevertheless exhibited a robust perceptual asymmetry in
      response to the indistinguishable facing orientations, similar to those who could
      consciously discriminate such 3D information. These results clearly demonstrate
      that the visual processing of biological motion engages the disparity cues
      independent of observers' depth awareness. The extraction and utilization of
      binocular depth signals thus can be dissociable from the conscious representation
      of 3D structure in high-level visual perception. 

PMID- 24586623
TI  - A novel mutation in the TECTA gene in a Chinese family with autosomal dominant
      nonsyndromic hearing loss.
AB  - TECTA-related deafness can be inherited as autosomal-dominant nonsyndromic
      deafness (designated DFNA) or as the autosomal-recessive version. The alpha
      tectorin protein, which is encoded by the TECTA gene, is one of the major
      components of the tectorial membrane in the inner ear. Using targeted DNA capture
      and massively parallel sequencing (MPS), we screened 42 genes known to be
      responsible for human deafness in a Chinese family (Family 3187) in which common
      deafness mutations had been ruled out as the cause, and identified a novel
      mutation, c.257-262CCTTTC>GCT (p. Ser86Cys; p. Pro88del) in exon 3 of the TECTA
      gene in the proband and his extended family. All affected individuals in this
      family had moderate down-sloping hearing loss across all frequencies. To our
      knowledge, this is the second TECTA mutation identified in Chinese population.
      This study demonstrates that targeted genomic capture, MPS, and barcode
      technology might broaden the availability of genetic testing for individuals with
      undiagnosed DFNA. 

PMID- 24586624
TI  - CLAVATA3 dodecapeptide modified CdTe nanoparticles: a biocompatible quantum dot
      probe for in vivo labeling of plant stem cells.
AB  - CLAVATA3 (CLV3) dodecapeptides function in plant stem cell maintenance, but CLV3
      function in cell-cell communication remains less clear. Here, we coupled CLV3
      dodecapeptides to synthesized CdTe nanoparticles to track their bioactivity on
      stem cells in the root apical meristem. To achieve this, we first synthesized
      CdTe quantum dots (QDs) using a one-pot method, and then evaluated the
      cytotoxicity of the QDs in BY-2 cells. The results showed that QDs in plant cells
      must be used at low concentrations and for short treatment time. To make
      biocompatible probes to track stem cell fate, we conjugated CLV3 dodecapeptides
      to the QDs by the zero-coupling method; this modification greatly reduced the
      cytotoxicity of the QDs. Furthermore, we detected CLV3-QDs localized on the cell
      membrane, consistent with the known localization of CLV3. Our results indicate
      that using surface-modified QDs at low concentrations and for short time
      treatment can improve their utility for plant cell imaging. 

PMID- 24586625
TI  - The plastered skulls from the Pre-Pottery Neolithic B site of Yiftahel (Israel)-
      a computed tomography-based analysis.
AB  - Three plastered skulls, dating to the Pre-Pottery Neolithic B, were found at the
      site of Yiftahel, in the Lower Galilee (Israel). The skulls underwent refitting
      and restoration processes, details of which are described herein. All three
      belong to adults, of which two appear to be males and one appears to be a female.
      Virtual cross-sections were studied and a density analysis of the plaster was
      performed using computed tomography scans. These were utilized to yield
      information regarding the modeling process. Similarities and differences between
      the Yiftahel and other plastered skulls from the Levant are examined. The
      possible role of skull plastering within a society undergoing a shift from a
      hunting-gathering way of life to a food producing strategy is discussed. 

PMID- 24586626
TI  - Inferring the temporal order of cancer gene mutations in individual tumor
      samples.
AB  - The temporal order of cancer gene mutations in tumors is essential for
      understanding and treating the disease. Existing methods are unable to infer the
      order of mutations that are identified at the same time in individual tumor
      samples, leaving the heterogeneity of the order unknown. Here, we show that
      through a complex network-based approach, which is based on the newly defined
      statistic -carcinogenesis information conductivity (CIC), the temporal order in
      individual samples can be effectively inferred. The results suggest that tumor
      suppressor genes might more frequently initiate the order of mutations than
      oncogenes, and every type of cancer might have its own unique order of mutations.
      The initial mutations appear to be dedicated to acquiring the function of evading
      apoptosis, and some order constraints might reflect potential regularities. Our
      approach is completely data-driven without any parameter settings and can be
      expected to become more effective as more data will become available. 

PMID- 24586627
TI  - Spatial variation as a tool for inferring temporal variation and diagnosing types
      of mechanisms in ecosystems.
AB  - Ecological processes, like the rise and fall of populations, leave an imprint of
      their dynamics as a pattern in space. Mining this spatial record for insight into
      temporal change underlies many applications, including using spatial snapshots to
      infer trends in communities, rates of species spread across boundaries,
      likelihood of chaotic dynamics, and proximity to regime shifts. However, these
      approaches rely on an inherent but undefined link between spatial and temporal
      variation. We present a quantitative link between a variable's spatial and
      temporal variation based on established variance-partitioning techniques, and
      test it for predictive and diagnostic applications. A strong link existed between
      spatial and regional temporal variation (estimated as Coefficients of Variation
      or CV's) in 136 variables from three aquatic ecosystems. This association
      suggests a basis for substituting one for the other, either quantitatively or
      qualitatively, when long time series are lacking. We further show that weak
      substitution of temporal for spatial CV results from distortion by specific
      spatiotemporal patterns (e.g., inter-patch synchrony). Where spatial and temporal
      CV's do not match, we pinpoint the spatiotemporal causes of deviation in the
      dynamics of variables and suggest ways that may control for them. In turn, we
      demonstrate the use of this framework for describing spatiotemporal patterns in
      multiple ecosystem variables and attributing them to types of mechanisms. Linking
      spatial and temporal variability makes quantitative the hitherto inexact practice
      of space-for-time substitution and may thus point to new opportunities for
      navigating the complex variation of ecosystems. 

PMID- 24586628
TI  - PalmPred: an SVM based palmitoylation prediction method using sequence profile
      information.
AB  - Protein palmitoylation is the covalent attachment of the 16-carbon fatty acid
      palmitate to a cysteine residue. It is the most common acylation of protein and
      occurs only in eukaryotes. Palmitoylation plays an important role in the
      regulation of protein subcellular localization, stability, translocation to lipid
      rafts and many other protein functions. Hence, the accurate prediction of
      palmitoylation site(s) can help in understanding the molecular mechanism of
      palmitoylation and also in designing various related experiments. Here we present
      a novel in silico predictor called 'PalmPred' to identify palmitoylation sites
      from protein sequence information using a support vector machine model. The best
      performance of PalmPred was obtained by incorporating sequence conservation
      features of peptide of window size 11 using a leave-one-out approach. It helped
      in achieving an accuracy of 91.98%, sensitivity of 79.23%, specificity of 94.30%,
      and Matthews Correlation Coefficient of 0.71. PalmPred outperformed existing
      palmitoylation site prediction methods - IFS-Palm and WAP-Palm on an independent
      dataset. Based on these measures it can be anticipated that PalmPred will be
      helpful in identifying candidate palmitoylation sites. All the source datasets,
      standalone and web-server are available at http://14.139.227.92/mkumar/palmpred/.

PMID- 24586629
TI  - Loss of Grainy head-like 1 is associated with disruption of the epidermal barrier
      and squamous cell carcinoma of the skin.
AB  - The Grainyhead-like 1 (GRHL1) transcription factor regulates the expression of
      desmosomal cadherin desmoglein 1 (Dsg1) in suprabasal layers of the epidermis. As
      a consequence, the epidermis of Grhl1-null mice displays fewer desmosomes that
      are abnormal in structure. These mice also exhibit mild chronic skin barrier
      defects as evidenced by altered keratinocyte terminal differentiation, increased
      expression of inflammatory markers and infiltration of the skin by immune cells.
      Exposure of Grhl1 (-/-) mice to a standard chemical skin carcinogenesis protocol
      results in development of fewer papillomas than in wild type control animals, but
      with a rate of conversion to squamous cell carcinoma (SCC) that is strikingly
      higher than in normal littermates. The underlying molecular mechanism differs
      from mice with conditional ablation of a closely related Grhl family member,
      Grhl3, in the skin, which develop SCC due to the loss of expression of
      phosphatase and tensin homolog (PTEN) and activation of the phosphatidylinositol
      3-kinase (PI3K)/AKT/mechanistic target of rapamycin (mTOR) signaling pathway. 

PMID- 24586630
TI  - Inhibitory effects of palm tocotrienol-rich fraction supplementation on bilirubin
      metabolizing enzymes in hyperbilirubinemic adult rats.
AB  - BACKGROUND: Phenylhydrazine, a hemolytic agent, is widely used as a model of
      experimental hyperbilirubinemia. Palm tocotrienol-rich fraction (TRF) was shown
      to exert beneficial effects in hyperbilirubinemic rat neonates. AIM: To
      investigate the effects of palm TRF supplementation on hepatic bilirubin
      metabolizing enzymes and oxidative stress status in rats administered
      phenylhydrazine. METHODS: Twenty-four male Wistar rats were divided into two
      groups; one group was intraperitoneally injected with palm TRF at the dose of 30
      mg/kg/day, while another group was only given vehicle (control) (vitamin E-free
      palm oil) for 14 days. Twenty-four hours after the last dose, each group was
      further subdivided into another two groups. One group was administered
      phenylhydrazine (100 mg/kg, intraperitoneally) and another group was administered
      normal saline. Twenty-four hours later, blood and liver were collected for
      biochemical parameter measurements. RESULTS: Phenylhydrazine increased plasma
      total bilirubin level and oxidative stress in the erythrocytes as well as in the
      liver, which were reduced by the pretreatment of palm TRF. Palm TRF also
      prevented the increases in hepatic heme oxygenase, biliverdin reductase and UDP
      glucuronyltransferase activities induced by phenylhydrazine. CONCLUSION: Palm
      tocotrienol-rich fraction was able to afford protection against phenylhydrazine
      induced hyperbilirubinemia, possibly by reducing oxidative stress and inhibiting
      bilirubin-metabolizing enzymes in the liver.

PMID- 24586631
TI  - Cryptococcus neoformans is internalized by receptor-mediated or 'triggered'
      phagocytosis, dependent on actin recruitment.
AB  - Cryptococcosis by the encapsulated yeast Cryptococcus neoformans affects mostly
      immunocompromised individuals and is a frequent neurological complication in AIDS
      patients. Recent studies support the idea that intracellular survival of
      Cryptococcus yeast cells is important for the pathogenesis of cryptococcosis.
      However, the initial steps of Cryptococcus internalization by host cells remain
      poorly understood. Here, we investigate the mechanism of Cryptococcus neoformans
      phagocytosis by peritoneal macrophages using confocal and electron microscopy
      techniques, as well as flow cytometry quantification, evaluating the importance
      of fungal capsule production and of host cell cytoskeletal elements for fungal
      phagocytosis. Electron microscopy analyses revealed that capsular and acapsular
      strains of C. neoformans are internalized by macrophages via both 'zipper'
      (receptor-mediated) and 'trigger' (membrane ruffle-dependent) phagocytosis
      mechanisms. Actin filaments surrounded phagosomes of capsular and acapsular
      yeasts, and the actin depolymerizing drugs cytochalasin D and latrunculin B
      inhibited yeast internalization and actin recruitment to the phagosome area. In
      contrast, nocodazole and paclitaxel, inhibitors of microtubule dynamics decreased
      internalization but did not prevent actin recruitment to the site of
      phagocytosis. Our results show that different uptake mechanisms, dependent on
      both actin and tubulin dynamics occur during yeast internalization by
      macrophages, and that capsule production does not affect the mode of Cryptococcus
      uptake by host cells. 

PMID- 24586632
TI  - Nuclear interaction between ADR-induced p65 and p53 mediates cardiac injury in
      iNOS (-/-) mice.
AB  - Adriamycin (ADR) treatment causes an imbalance in the levels of nitric oxide
      ((*)NO) and superoxide (O2(*-)) production leading to cardiac injury. Previously
      we demonstrated that mice lacking inducible nitric oxide synthase (iNOS) have
      increased oxidative stress and mitochondrial injury. The molecular events leading
      to increased mitochondrial injury in iNOS deficient mice is unknown. ADR in the
      absence of iNOS preferentially activates a proapoptotic pathway without a
      concurrent increase in prosurvival pathways. Treatment with ADR leads to an
      increase in DNA binding activity of nuclear factor kappa B (NFkappaB) and p53 in
      wildtype mice. Following ADR treatment, p53, but not NFkappaB DNA binding
      activity, as well as the level of Bax, a p53 target gene, was increased in iNOS (
      /-) mice. This apoptotic signaling effect in iNOS (-/-) is alleviated by
      overexpression of manganese superoxide dismutase (MnSOD). Increases in NFkappaB
      and p53 in ADR-treated wildtype mice did not lead to increases in target genes
      such as MnSOD, bcl-xL, or Bax. Moreover, co-immunoprecipitation analysis revealed
      that p65, a prominent member of the NFkappaB family, interacts with p53 in the
      nucleus. These results suggest that NFkappaB and p53 may counter act one
      another's actions in ADR-treated wildtype (WT) mice. Further, these results
      identify a novel mechanism by which oxidative stress may regulate transcription
      of proapoptotic genes.

PMID- 24586633
TI  - Genetic association analysis of ATP binding cassette protein family reveals a
      novel association of ABCB1 genetic variants with epilepsy risk, but not with drug
      resistance.
AB  - Epilepsy constitutes a heterogeneous group of disorders that is characterized by
      recurrent unprovoked seizures due to widely different etiologies. Multidrug
      resistance remains a major issue in clinical epileptology, where one third of
      patients with epilepsy continue to have seizures. Role of efflux transporters in
      multidrug resistant epilepsy has been attributed to drug-resistant epilepsy
      although, with discrepant observation in genetic studies. These discrepancies
      could be attributed to variety of factors such as variable definition of the anti
      epileptic drug (AED)-resistance, variable epilepsy phenotypes and ethnicities
      among the studies. In the present study we inquired the role of multidrug
      transporters ABCB1 and ABCG2 variants in determining AED-resistance and
      susceptibility to epilepsy in three well-characterized cohorts comprising of
      mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) (prototype for
      AED-resistant epilepsy); juvenile myoclonic epilepsy (JME) (prototype for AED
      responsive epilepsy); and healthy non-epileptic controls, in 738 subjects of
      Malayalam speaking south Indian ancestry. ABCB1 and ABCG2 variants were not found
      to be associated with drug resistance when AED-resistant and AED-responsive
      cohorts were compared. However, a significant association was observed between
      ABCB1 (C3435T) rs1045642 and risk of having epilepsy (MTLE-HS and JME pooled
      cohort; genotypic p-value = 0.0002; allelic p-value = 0.004). This association
      was seen persistent with MTLE-HS (genotypic p-value = 0.0008; allelic p-value =
      0.004) and also with JME (genotypic p-value = 0.01; allelic p-value = 0.05)
      cohort individually. In-silico functional prediction indicated that ABCB1
      rs1045642 has a deleterious impact on protein coding function and in splicing
      regulation. We conclude that the ABCB1 and ABCG2 variants do not confer to AED
      resistance in the study population. However, ABCB1 rs1045642 increases
      vulnerability to epilepsy with greater tendency for MTLE-HS in south Indian
      ancestry from Kerala.

PMID- 24586634
TI  - Geographic variation in sexual attraction of Spodoptera frugiperda corn- and rice
      strain males to pheromone lures.
AB  - The corn- and rice-strains of Spodoptera frugiperda exhibit several genetic and
      behavioral differences and appear to be undergoing ecological speciation in
      sympatry. Previous studies reported conflicting results when investigating male
      attraction to pheromone lures in different regions, but this could have been due
      to inter-strain and/or geographic differences. Therefore, we investigated whether
      corn- and rice-strain males differed in their response to different synthetic
      pheromone blends in different regions in North America, the Caribbean and South
      America. All trapped males were strain-typed by two strain-specific mitochondrial
      DNA markers. In the first experiment, we found a nearly similar response of corn-
      and rice-strain males to two different 4-component blends, resembling the corn-
      and rice-strain female blend we previously described from females in Florida.
      This response showed some geographic variation in fields in Canada, North
      Carolina, Florida, Puerto Rico, and South America (Peru, Argentina). In dose
      response experiments with the critical secondary sex pheromone component (Z)-7
      dodecenyl acetate (Z7-12:OAc), we found some strain-specific differences in male
      attraction. While the response to Z7-12:OAc varied geographically in the corn
      strain, rice-strain males showed almost no variation. We also found that the
      minor compound (Z)-11-hexadecenyl acetate (Z11-16:OAc) did not increase
      attraction of both strains in Florida and of corn-strain males in Peru. In a
      fourth experiment, where we added the stereo-isomer of the critical sex pheromone
      component, (E)-7-dodecenyl acetate, to the major pheromone component (Z)-9
      tetradecenyl acetate (Z9-14:OAc), we found that this compound was attractive to
      males in North Carolina, but not to males in Peru. Overall, our results suggest
      that both strains show rather geographic than strain-specific differences in
      their response to pheromone lures, and that regional sexual communication
      differences might cause geographic differentiation between populations. 

PMID- 24586635
TI  - Determinants of gastroesophageal reflux disease, including hookah smoking and
      opium use- a cross-sectional analysis of 50,000 individuals.
AB  - BACKGROUND: Gastroesophageal reflux disease (GERD) is a common cause of
      discomfort and morbidity worldwide. However, information on determinants of GERD
      from large-scale studies in low- to medium-income countries is limited. We
      investigated the factors associated with different measures of GERD symptoms,
      including frequency, patient-perceived severity, and onset time. METHODS: We
      performed a cross-sectional analysis of the baseline data from a population-based
      cohort study of ~ 50,000 individuals in in Golestan Province, Iran. GERD symptoms
      in this study included regurgitation and/or heartburn. RESULTS: Approximately 20%
      of participants reported at least weekly symptoms. Daily symptoms were less
      commonly reported by men, those of Turkmen ethnicity, and nass chewers. On the
      other hand, age, body mass index, alcohol drinking, cigarette smoking, opium use,
      lower socioeconomic status, and lower physical activity were associated with
      daily symptoms. Most of these factors showed similar associations with severe
      symptoms. Women with higher BMI and waist to hip ratio were more likely to report
      frequent and severe GERD symptoms. Hookah smoking (OR 1.34, 95% CI 1.02-1.75) and
      opium use (OR 1.70, 95% CI 1.55-1.87) were associated with severe symptoms,
      whereas nass chewing had an inverse association (OR 0.87, 95% CI 0.76-0.99).
      After exclusion of cigarette smokers, hookah smoking was still positively
      associated and nass chewing was inversely associated with GERD symptoms (all
      frequencies combined). CONCLUSION: GERD is common in this population. The
      associations of hookah and opium use and inverse association of nass use with
      GERD symptoms are reported for the first time. Further studies are required to
      investigate the nature of these associations. Other determinants of GERD were
      mostly comparable to those reported elsewhere.

PMID- 24586636
TI  - Enhanced neurogenesis in the hippocampal dentate gyrus during antigen-induced
      arthritis in adult rat--a crucial role of immunization.
AB  - Neurogenesis in the subgranular zone of the mammalian hippocampal dentate gyrus
      contributes significantly to brain neuroplasticity. There is evidence that
      inflammation of the central nervous system inhibits neurogenesis but peripheral
      inflammation such as antigen-induced arthritis may rather enhance neurogenesis.
      Manifest arthritis is associated with symptoms such as pain and altered
      locomotion indicating that peripheral inflammation is associated with changes of
      both the immune system and the nervous system. This raises the intriguing
      question whether immune or neuronal factors or both actually drive changes of
      neurogenesis. Here we explored hippocampal neurogenesis in the rat during chronic
      antigen-induced arthritis in the knee joint. We analyzed neurogenesis in control
      rats, and in rats which were immunized for the antigen producing arthritis but
      which did not show arthritis and neurological symptoms, and in rats in which
      antigen injection into the knee produced manifest local inflammation and symptoms
      such as pain at the inflamed knee and altered locomotor behavior. Neurogenesis
      was assessed by quantifying bromodeoxyuridine-positive cells in sections of the
      complete hippocampal dentate gyrus. Compared to control animals, rats with
      antigen-induced arthritis presenting manifest local inflammation, hyperalgesia at
      the inflamed knee and significantly altered locomotion exhibited a significant
      increase of bromodeoxyuridine-positive cells. However, a similar increase in the
      number of such cells was found in rats which were only immunized against the
      antigen, but in which no local inflammatory response was induced and which
      thereby neither showed hyperalgesia nor alterations of locomotion. Thus we
      conclude that in peripheral immune-mediated arthritis the activation of the
      immune system in the process of immunization is the causal factor driving
      enhanced neurogenesis, and neither the local enhancement of inflammation nor the
      activation of the nervous system leading to neurological symptoms such as pain
      and altered locomotion. It seems noteworthy to further explore the clinical
      importance of this neuroimmune interaction. 

PMID- 24586638
TI  - Synthetic LPETG-containing peptide incorporation in the Staphylococcus aureus
      cell-wall in a sortase A- and growth phase-dependent manner.
AB  - The majority of Staphylococcus aureus virulence- and colonization-associated
      surface proteins contain a pentapeptide recognition motif (LPXTG). This motif can
      be recognized and cleaved by sortase A (SrtA) which is a membrane-bound
      transpeptidase. After cleavage these proteins are covalently incorporated into
      the peptidoglycan. Therefore, SrtA plays a key role in S. aureus virulence. We
      aimed to generate a substrate mimicking this SrtA recognition motif for several
      purposes: to incorporate this substrate into the S. aureus cell-wall in a SrtA
      dependent manner, to characterize this incorporation and to determine the effect
      of substrate incorporation on the incorporation of native SrtA-dependent cell
      surface-associated proteins. We synthesized substrate containing the specific
      LPXTG motif, LPETG. As a negative control we used a scrambled version of this
      substrate, EGTLP and a S. aureus srtA knockout strain. Both substrates contained
      a fluorescence label for detection by FACScan and fluorescence microscope. A
      spreading assay and a competitive Luminex assay were used to determine the effect
      of substrate treatment on native LPXTG containing proteins deposition in the
      bacterial cell-wall. We demonstrate a SrtA-dependent covalent incorporation of
      the LPETG-containing substrate in wild type S. aureus strains and several other
      Gram-positive bacterial species. LPETG-containing substrate incorporation in S.
      aureus was growth phase-dependent and peaked at the stationary phase. This
      incorporation negatively correlated with srtA mRNA expression. Exogenous addition
      of the artificial substrate did not result in a decreased expression of native
      SrtA substrates (e.g. clumping factor A/B and protein A) nor induced a srtA
      knockout phenotype. 

PMID- 24586637
TI  - Prognostic significance of lymphovascular invasion in radical cystectomy on
      patients with bladder cancer: a systematic review and meta-analysis.
AB  - PURPOSE: The objective of the present study was to conduct a systematic review
      and meta-analysis of published literature to appraise the prognostic value of
      lymphovascular invasion (LVI) in radical cystectomy specimens. MATERIALS AND
      METHODS: Following the PRISMA statement, PubMed, Cochrane Library, and SCOPUS
      database were searched from the respective dates of inception until June 2013.
      RESULTS: A total of 21 articles met the eligibility criteria for this systematic
      review, which included a total of 12,527 patients ranging from 57 to 4,257 per
      study. LVI was detected in 34.6% in radical cystectomy specimens. LVI was
      associated with higher pathological T stage and tumor grade, as well as lymph
      node metastasis. The pooled hazard ratio (HR) was statistically significant for
      recurrence-free survival (pooled HR, 1.61; 95% confidence interval [CI], 1.26
      2.06), cancer-specific survival (pooled HR, 1.67; 95% CI, 1.38-2.01), and overall
      survival (pooled HR, 1.67; 95% CI, 1.38-2.01), despite the heterogeneity among
      included studies. On sensitivity analysis, the pooled HRs and 95% CIs were not
      significantly altered when any one study was omitted. The funnel plot for overall
      survival demonstrated a certain degree of asymmetry, which showed slight
      publication bias. CONCLUSIONS: This meta-analysis indicates that LVI is
      significantly associated with poor outcome in patients with bladder cancer who
      underwent radical cystectomy. Adequately designed prospective studies are
      required to provide the precise prognostic significance of LVI in bladder cancer.

PMID- 24586639
TI  - Highly prevalent LIPH founder mutations causing autosomal recessive woolly
      hair/hypotrichosis in Japan and the genotype/phenotype correlations.
AB  - Mutations in LIPH cause of autosomal recessive woolly hair/hypotrichosis (ARWH),
      and the 2 missense mutations c.736T>A (p.Cys246Ser) and c.742C>A (p.His248Asn)
      are considered prevalent founder mutations for ARWH in the Japanese population.
      To reveal genotype/phenotype correlations in ARWH cases in Japan and the
      haplotypes in 14 Japanese patients from 14 unrelated Japanese families. 13
      patients had woolly hair, and 1 patient had complete baldness since birth. An
      LIPH mutation search revealed homozygous c.736T>A mutations in 10 of the
      patients. Compound heterozygous c.736T>A and c.742C>A mutations were found in 3
      of the patients, and homozygous c.742C>A mutation in 1 patient. The phenotype of
      mild hypotrichosis with woolly hair was restricted to the patients with the
      homozygous c.736T>A mutation. The severe phenotype of complete baldness was seen
      in only 1 patient with homozygous c.742C>A. Haplotype analysis revealed that the
      alleles containing the LIPH c.736T>A mutation had a haplotype identical to that
      reported previously, although 4 alleles out of 5 chromosomes containing the LIPH
      c.742C>A mutation had a different haplotype from the previously reported founder
      allele. These alleles with c.742C>A are thought to be the third founder LIPH
      mutation causing ARWH. To accurately determine the prevalence of the founder
      mutations, we investigated allele frequencies of those mutations in 819 Japanese
      controls. Heterozygous c.736T>A mutations were found in 13 controls (allele
      frequency: 0.0079; carrier rate: 0.016), and heterozygous c.742C>A mutations were
      found in 2 controls (allele frequency: 0.0012; carrier rate: 0.0024). In
      conclusion, this study confirms the more accurate allele frequencies of the
      pathogenic founder mutations of LIPH and shows that there is a third founder
      mutation in Japan. In addition, the present findings suggest that the mutation
      patterns of LIPH might be associated with hypotrichosis severity in ARWH. 

PMID- 24586640
TI  - A core invasiveness gene signature reflects epithelial-to-mesenchymal transition
      but not metastatic potential in breast cancer cell lines and tissue samples.
AB  - INTRODUCTION: Metastases remain the primary cause of cancer-related death. The
      acquisition of invasive tumour cell behaviour is thought to be a cornerstone of
      the metastatic cascade. Therefore, gene signatures related to invasiveness could
      aid in stratifying patients according to their prognostic profile. In the present
      study we aimed at identifying an invasiveness gene signature and investigated its
      biological relevance in breast cancer. METHODS & RESULTS: We collected a set of
      published gene signatures related to cell motility and invasion. Using this
      collection, we identified 16 genes that were represented at a higher frequency
      than observed by coincidence, hereafter named the core invasiveness gene
      signature. Principal component analysis showed that these overrepresented genes
      were able to segregate invasive and non-invasive breast cancer cell lines,
      outperforming sets of 16 randomly selected genes (all P<0.001). When applied onto
      additional data sets, the expression of the core invasiveness gene signature was
      significantly elevated in cell lines forced to undergo epithelial-mesenchymal
      transition. The link between core invasiveness gene expression and epithelial
      mesenchymal transition was also confirmed in a dataset consisting of 2420 human
      breast cancer samples. Univariate and multivariate Cox regression analysis
      demonstrated that CIG expression is not associated with a shorter distant
      metastasis free survival interval (HR = 0.956, 95%C.I. = 0.896-1.019, P = 0.186).
      DISCUSSION: These data demonstrate that we have identified a set of core
      invasiveness genes, the expression of which is associated with epithelial
      mesenchymal transition in breast cancer cell lines and in human tissue samples.
      Despite the connection between epithelial-mesenchymal transition and invasive
      tumour cell behaviour, we were unable to demonstrate a link between the core
      invasiveness gene signature and enhanced metastatic potential.

PMID- 24586641
TI  - T cell receptor signaling can directly enhance the avidity of CD28 ligand
      binding.
AB  - T cell activation takes place in the context of a spatial and kinetic
      reorganization of cell surface proteins and signaling molecules at the contact
      site with an antigen presenting cell, termed the immunological synapse.
      Coordination of the activation, recruitment, and signaling from T cell receptor
      (TCR) in conjunction with adhesion and costimulatory receptors regulates both the
      initiation and duration of signaling that is required for T cell activation. The
      costimulatory receptor, CD28, is an essential signaling molecule that determines
      the quality and quantity of T cell immune responses. Although the functional
      consequences of CD28 engagement are well described, the molecular mechanisms that
      regulate CD28 function are largely unknown. Using a micropipet adhesion frequency
      assay, we show that TCR signaling enhances the direct binding between CD28 and
      its ligand, CD80. Although CD28 is expressed as a homodimer, soluble recombinant
      CD28 can only bind ligand monovalently. Our data suggest that the increase in
      CD28-CD28 binding is mediated through a change in CD28 valency. Molecular dynamic
      simulations and in vitro mutagenesis indicate that mutations at the base of the
      CD28 homodimer interface, distal to the ligand-binding site, can induce a change
      in the orientation of the dimer that allows for bivalent ligand binding. When
      expressed in T cells, this mutation allows for high avidity CD28-CD80
      interactions without TCR signaling. Molecular dynamic simulations also suggest
      that wild type CD28 can stably adopt a bivalent conformation. These results
      support a model whereby inside-out signaling from the TCR can enhance CD28 ligand
      interactions by inducing a change in the CD28 dimer interface to allow for
      bivalent ligand binding and ultimately the transduction of CD28 costimulatory
      signals that are required for T cell activation. 

PMID- 24586642
TI  - The expression and characterization of functionally active soluble CD83 by Pichia
      pastoris using high-density fermentation.
AB  - CD83 is a highly glycosylated type I transmembrane glycoprotein that belongs to
      the immunoglobulin superfamily. CD83 is upregulated during dendritic cell (DC)
      maturation, which is critical for the initiation of adaptive immune responses.
      The soluble isoform of CD83 (sCD83) is encoded by alternative splicing from full
      length CD83 mRNA and inhibits DC maturation, which suggests that sCD83 acts as a
      potential immune suppressor. In this study, we developed a sound strategy to
      express functional sCD83 from Pichia pastoris in extremely high-density
      fermentation. Purified sCD83 was expressed as a monomer at a yield of more than
      200 mg/L and contained N-linked glycosylation sites that were characterized by
      PNGase F digestion. In vitro tests indicated that recombinant sCD83 bound to its
      putative counterpart on monocytes and specifically blocked the binding of anti
      CD83 antibodies to cell surface CD83 on DCs. Moreover, sCD83 from yeast
      significantly suppressed ConA-stimulated PBMC proliferation. Therefore, sCD83
      that was expressed from the P. pastoris was functionally active and may be used
      for in vivo and in vitro studies as well as future clinical applications. 

PMID- 24586643
TI  - Duplicated female receptacle organs for traumatic insemination in the tropical
      bed bug Cimex hemipterus: adaptive variation or malformation?
AB  - During mating, male bed bugs (Cimicidae) pierce the female abdomen to inject
      sperm using their needle-like genitalia. Females evolved specialized paragenital
      organs (the spermalege and associated structures) to receive traumatically
      injected ejaculates. In Leptocimex duplicatus, the spermalege is duplicated, but
      the evolutionary significance of this is unclear. In Cimex hemipterus and C.
      lectularius, in which females normally develop a single spermalege on the right
      side of the abdomen, similar duplication sometimes occurs. Using these aberrant
      morphs (D-females) of C. hemipterus, we tested the hypothesis that both of the
      duplicated spermaleges are functionally competent. Scars on female abdominal
      exoskeletons indicated frequent misdirected piercing by male genitalia. However,
      the piercing sites showed a highly biased distribution towards the right side of
      the female body. A mating experiment showed that when the normal insemination
      site (the right-side spermalege) was artificially covered, females remained
      unfertilized. This was true even when females also had a spermalege on the left
      side (D-females). This result was attributed to handedness in male mating
      behavior. Irrespective of the observed disuse of the left-side spermalege by
      males for insemination, histological examination failed to detect any differences
      between the right-side and left-side spermaleges. Moreover, an artificial
      insemination experiment confirmed that spermatozoa injected into the left-side
      spermalege show apparently normal migration behavior to the female reproductive
      organs, indicating an evolutionary potential for functionally-competent
      duplicated spermaleges. We discuss possible mechanisms for the evolutionary
      maintenance of D-females and propose a plausible route to the functionally
      competent duplicated spermaleges observed in L. duplicatus. 

PMID- 24586644
TI  - Abrogation of Rbpj attenuates experimental autoimmune uveoretinitis by inhibiting
      IL-22-producing CD4+ T cells.
AB  - Experimental autoimmune uveoretinitis (EAU) is an organ-specific T cell-mediated
      disease induced by immunizing mice with interphotoreceptor retinoid binding
      protein (IRBP). Autoaggressive CD4(+) T cells are the major pathogenic population
      for EAU. We investigated the contribution of Notch signaling in T cells to EAU
      pathogenesis because Notch signaling regulates various aspects of CD4(+) T cell
      functions. Rbpj is required for Notch signaling, and Rbpj deficiency in T cells
      inhibited EAU disease severity. The amelioration of EAU in T cell-specific Rbpj
      deficient mice correlated with low levels of IL-22 production from CD4(+) T
      cells, although IRBP-specific CD4(+) T cell proliferation and Th17
      differentiation were unaffected. Administration of recombinant IL-22 during the
      late phase, but not the early phase, of EAU increased EAU clinical scores in T
      cell-specific Rbpj-deficient mice. Notch inhibition in mice immunized with IRBP
      with a gamma-secretase inhibitor (GSI) suppressed EAU progression, even when GSI
      was administered as late as 13 days after IRBP immunization. Our data demonstrate
      that Rbpj/Notch-mediated IL-22 production in T cells has a key pathological role
      in the late phase of EAU, and suggest that Notch blockade might be a useful
      therapeutic approach for treating EAU. 

PMID- 24586645
TI  - Clinical, molecular and functional investigation on an infant with neonatal
      intrahepatic cholestasis caused by citrin deficiency (NICCD).
AB  - BACKGROUND AND OBJECTIVE: SLC25A13 analysis has provided reliable evidences for
      the definitive diagnosis of citrin deficiency (CD) in the past decade. Meanwhile,
      these studies generated some issues yet to be resolved, including the
      pathogenicity of SLC25A13 missense mutations and the mRNA product from the
      mutation c.615+5G>A. This study aims to investigate the effect of a novel
      missense mutation on the aspartate/glutamate carrier (AGC) function of citrin
      protein, and to explore the aberrant transcript from c.615+5G>A in the same CD
      infant. METHODS AND RESULTS: By means of screening for prevalent SLC25A13
      mutations and exons sequencing, the patient proved a compound heterozygote of
      c.615+5G>A and a novel c.1064G>A (p.Arg355Gln) mutation. An aberrant transcript
      with retention of the entire intron 6, r.[615+1_615+1789ins; 615+5 g>a] (GenBank
      accession number KJ128074), which was resulted from c.615+5G>A, was detected by
      RT-PCR and cDNA sequencing. After bioinformatic analyses of the novel missense
      mutation c.1064G>A, the growth abilities of three agc1Delta yeast strains were
      tested, which had been transformed with recombinant or empty vectors,
      respectively. Besides the bioinformatically pathogenic evidences, the growth
      ability of the agc1Delta strains transformed with mutant recombinant was the same
      as with empty vector, but significantly lower than that with normal control in
      functional analysis. CONCLUSIONS: A CD infant was definitely diagnosed in this
      paper by a genetic, transcriptional and functional analysis of SLC25A13 gene.
      This study provided direct laboratory evidences supporting the splice-site nature
      of the c.615+5G>A mutation, and the novel c.1064G>A variation, which proved a
      pathogenic mutation bioinformatically and functionally, enriched the SLC25A13
      mutation spectrum.

PMID- 24586646
TI  - Mouse models for pseudoxanthoma elasticum: genetic and dietary modulation of the
      ectopic mineralization phenotypes.
AB  - Pseudoxanthoma elasticum (PXE), a heritable ectopic mineralization disorder, is
      caused by mutations in the ABCC6 gene. Null mice (Abcc6(-/-) ) recapitulate the
      genetic, histopathologic and ultrastructural features of PXE, and they
      demonstrate early and progressive mineralization of vibrissae dermal sheath,
      which serves as a biomarker of the overall mineralization process. Recently, as
      part of a mouse aging study at The Jackson Laboratory, 31 inbred mouse strains
      were necropsied, and two of them, KK/HlJ and 129S1/SvImJ, were noted to have
      vibrissae dermal mineralization similar to Abcc6(-/-) mice. These two strains
      were shown to harbor a single nucleotide polymorphism (rs32756904) in the Abcc6
      gene, which resulted in out-of-frame splicing and marked reduction in ABCC6
      protein expression in the liver of these mice. The same polymorphism is present
      in two additional mouse strains, DBA/2J and C3H/HeJ, with similar reduction in
      Abcc6 protein levels, yet these mice did not demonstrate tissue mineralization
      when kept on standard rodent diet. However, all four mouse strains, when placed
      on experimental diet enriched in phosphate and low in magnesium, developed
      extensive ectopic mineralization. These results indicate that the genetic
      background of mice and the mineral composition of their diet can profoundly
      modulate the ectopic mineralization process predicated on mutations in the Abcc6
      gene. These mice provide novel model systems to study the pathomechanisms and the
      reasons for strain background on phenotypic variability of PXE. 

PMID- 24586647
TI  - Plaque bacterial microbiome diversity in children younger than 30 months with or
      without caries prior to eruption of second primary molars.
AB  - OBJECTIVE: Our primary objective is to phylogenetically characterize the
      supragingival plaque bacterial microbiome of children prior to eruption of second
      primary molars by pyrosequencing method for studying etiology of early childhood
      caries. METHODS: Supragingival plaque samples were collected from 10 caries
      children and 9 caries-free children. Plaque DNA was extracted, used to generate
      DNA amplicons of the V1-V3 hypervariable region of the bacterial 16S rRNA gene,
      and subjected to 454-pyrosequencing. RESULTS: On average, over 22,000 sequences
      per sample were generated. High bacterial diversity was noted in the plaque of
      children with caries [170 operational taxonomical units (OTU) at 3% divergence]
      and caries-free children (201 OTU at 3% divergence) with no significant
      difference. A total of 8 phyla, 15 classes, 21 orders, 30 families, 41 genera and
      99 species were represented. In addition, five predominant phyla (Firmicute,
      Fusobacteria, Proteobacteria, Bacteroidetes and Actinobacteria) and seven genera
      (Leptotrichia, Streptococcus, Actinomyces, Prevotella, Porphyromonas, Neisseria,
      and Veillonella) constituted a majority of contents of the total microbiota,
      independent of the presence or absence of caries. Principal Component Analysis
      (PCA) presented that caries-related genera included Streptococcus and
      Veillonella; while Leptotrichia, Selenomonas, Fusobacterium, Capnocytophaga and
      Porphyromonas were more related to the caries-free samples. Neisseria and
      Prevotella presented approximately in between. In both groups, the degree of
      shared organism lineages (as defined by species-level OTUs) among individual
      supragingival plaque microbiomes was minimal. CONCLUSION: Our study represented
      for the first time using pyrosequencing to elucidate and monitor supragingival
      plaque bacterial diversity at such young age with second primary molar
      unerrupted. Distinctions were revealed between caries and caries-free microbiomes
      in terms of microbial community structure. We observed differences in abundance
      for several microbial groups between the caries and caries-free host populations,
      which were consistent with the ecological plaque hypothesis. Our approach and
      findings could be extended to correlating microbiomic changes after occlusion
      establishment and caries treatment.

PMID- 24586648
TI  - Conditional deletion of ferritin h in mice reduces B and T lymphocyte
      populations.
AB  - The immune system and iron availability are intimately linked as appropriate iron
      supply is needed for cell proliferation, while excess iron, as observed in
      hemochromatosis, may reduce subsets of lymphocytes. We have tested the effects of
      a ferritin H gene deletion on lymphocytes. Mx-Cre mediated conditional deletion
      of ferritin H in bone marrow reduced the number of mature B cells and peripheral
      T cells in all lymphoid organs. FACS analysis showed an increase in the labile
      iron pool, enhanced reactive oxygen species formation and mitochondrial
      depolarization. The findings were confirmed by a B-cell specific deletion using
      Fth(lox/lox) ; CD19-Cre mice. Mature B cells were strongly under-represented in
      bone marrow and spleen of the deleted mice, whereas pre-B and immature B cells
      were not affected. Bone marrow B cells showed increased proliferation as judged
      by the number of cells in S and G2/M phase as well as BrdU incorporation. Upon in
      vitro culture with B-cell activating factor of the tumor necrosis factor family
      (BAFF), ferritin H-deleted spleen B cells showed lower survival rates than wild
      type cells. This was partially reversed with iron-chelator deferiprone. The loss
      of T cells was also confirmed by a T cell-specific deletion in Fth(lox/lox) ;CD4
      Cre mice. Our data show that ferritin H is required for B and T cell survival by
      actively reducing the labile iron pool. They further suggest that natural B and T
      cell maturation is influenced by intracellular iron levels and possibly
      deregulated in iron excess or deprivation. 

PMID- 24586649
TI  - Socioeconomic status and stroke prevalence in Morocco: results from the Rabat
      Casablanca study.
AB  - BACKGROUND: Stroke is a growing public health concern in low- and middle- income
      countries. Improved knowledge about the association between socioeconomic status
      and stroke in these countries would enable the development of effective stroke
      prevention and management strategies. This study presents the association between
      socioeconomic status and the prevalence of stroke in Morocco, a lower middle
      income country. METHODS: Data on the prevalence of stroke and stroke-related risk
      factors were collected during a large population-based survey. The diagnosis of
      stroke in surviving patients was confirmed by neurologists while health,
      demographic, and socioeconomic characteristics of households were collected using
      structured questionnaires. We used Multiple Correspondence Analysis to develop a
      wealth index based on characteristics of the household dwelling as well as
      ownership of selected assets. We used logistic regressions controlling for
      multiple variables to assess the statistical association between socioeconomic
      status and stroke. FINDINGS: Our results showed a significant association between
      household socioeconomic status and the prevalence of stroke. This relationship
      was non-linear, with individuals from both the poorest (mainly rural) and richest
      (mainly urban) households having a lower prevalence of stroke as compared to
      individuals with medium wealth level. The latter belonged mainly to urban
      households with a lower socioeconomic status. When taking into account the urban
      population only, we observed that a third of poorest households experienced a
      significantly higher prevalence of stroke compared to the richest third (OR =
      2.06; CI 95%: 1.09; 3.89). CONCLUSION: We conclude that individuals from the most
      deprived urban households bear a higher risk of stroke than the rest of the
      population in Morocco. This result can be explained to a certain extent by the
      higher presence of behavioral risk factors in this specific category of the
      population, which leads in turn to metabolic and physiological risk factors of
      stroke, such as obesity, diabetes, and hypertension.

PMID- 24586651
TI  - Cross-modal matching of audio-visual German and French fluent speech in infancy.
AB  - The present study examined when and how the ability to cross-modally match audio
      visual fluent speech develops in 4.5-, 6- and 12-month-old German-learning
      infants. In Experiment 1, 4.5- and 6-month-old infants' audio-visual matching
      ability of native (German) and non-native (French) fluent speech was assessed by
      presenting auditory and visual speech information sequentially, that is, in the
      absence of temporal synchrony cues. The results showed that 4.5-month-old infants
      were capable of matching native as well as non-native audio and visual speech
      stimuli, whereas 6-month-olds perceived the audio-visual correspondence of native
      language stimuli only. This suggests that intersensory matching narrows for
      fluent speech between 4.5 and 6 months of age. In Experiment 2, auditory and
      visual speech information was presented simultaneously, therefore, providing
      temporal synchrony cues. Here, 6-month-olds were found to match native as well as
      non-native speech indicating facilitation of temporal synchrony cues on the
      intersensory perception of non-native fluent speech. Intriguingly, despite the
      fact that audio and visual stimuli cohered temporally, 12-month-olds matched the
      non-native language only. Results were discussed with regard to multisensory
      perceptual narrowing during the first year of life. 

PMID- 24586650
TI  - Transcription factor binding site analysis identifies FOXO transcription factors
      as regulators of the cutaneous wound healing process.
AB  - The search for significantly overrepresented and co-occurring transcription
      factor binding sites in the promoter regions of the most differentially expressed
      genes in microarray data sets could be a powerful approach for finding key
      regulators of complex biological processes. To test this concept, two previously
      published independent data sets on wounded human epidermis were re-analyzed. The
      presence of co-occurring transcription factor binding sites for FOXO1, FOXO3 and
      FOXO4 in the majority of the promoter regions of the most significantly
      differentially expressed genes between non-wounded and wounded epidermis implied
      an important role for FOXO transcription factors during wound healing. Expression
      levels of FOXO transcription factors during wound healing in vivo in both human
      and mouse skin were analyzed and a decrease for all FOXOs in human wounded skin
      was observed, with FOXO3 having the highest expression level in non wounded skin.
      Impaired re-epithelialization was found in cultures of primary human
      keratinocytes expressing a constitutively active variant of FOXO3. Conversely
      knockdown of FOXO3 in keratinocytes had the opposite effect and in an in vivo
      mouse model with FOXO3 knockout mice we detected significantly accelerated wound
      healing. This article illustrates that the proposed approach is a viable method
      for identifying important regulators of complex biological processes using in
      vivo samples. FOXO3 has not previously been implicated as an important regulator
      of wound healing and its exact function in this process calls for further
      investigation. 

PMID- 24586652
TI  - Verbal overshadowing of memories for fencing movements is mediated by expertise.
AB  - Does verbalizing a previously-seen complex visual stimulus influence its
      subsequent recollection? We investigated this question by examining the mediating
      role played by expertise level in fencing on the effects of verbalizing upon
      visual memory. Participants with three distinct levels of expertise in fencing
      (novices, intermediates, experts) performed seven trials. In each trial, they
      first watched four times a short video that displayed fencing movements. Then,
      half of them verbalized the previously-seen visual stimulus (i.e., the
      verbalization group), the other half carried out a hidden-word task (i.e., the
      non-verbalization group). Finally, all the participants were asked to recognize
      the previously-seen fencing movements amongst novel fencing movements. Overall,
      verbalizing improved recognition for novices, altered recognition for
      intermediates, and had no effect for experts. These findings replicated the
      classical verbal-overshadowing effect, while extending it to a more conceptual
      material. They also point out to some potential benefits and costs of verbalizing
      on visual memory, depending on the level of expertise. 

PMID- 24586653
TI  - Dystropathology increases energy expenditure and protein turnover in the mdx
      mouse model of duchenne muscular dystrophy.
AB  - The skeletal muscles in Duchenne muscular dystrophy and the mdx mouse model lack
      functional dystrophin and undergo repeated bouts of necrosis, regeneration, and
      growth. These processes have a high metabolic cost. However, the consequences for
      whole body energy and protein metabolism, and on the dietary requirements for
      these macronutrients at different stages of the disease, are not well-understood.
      This study used juvenile (4- to 5- wk-old) and adult (12- to 14-wk-old) male
      dystrophic C57BL/10ScSn-mdx/J and age-matched C57BL/10ScSn/J control male mice to
      measure total and resting energy expenditure, food intake, spontaneous activity,
      body composition, whole body protein turnover, and muscle protein synthesis
      rates. In juvenile mdx mice that have extensive muscle damage, energy
      expenditure, muscle protein synthesis, and whole body protein turnover rates were
      higher than in age-matched controls. Adaptations in food intake and decreased
      activity were insufficient to meet the increased energy and protein needs of
      juvenile mdx mice and resulted in stunted growth. In (non-growing) adult mdx mice
      with less severe dystropathology, energy expenditure, muscle protein synthesis,
      and whole body protein turnover rates were also higher than in age-matched
      controls. Food intake was sufficient to meet their protein and energy needs, but
      insufficient to result in fat deposition. These data show that dystropathology
      impacts the protein and energy needs of mdx mice and that tailored dietary
      interventions are necessary to redress this imbalance. If not met, the resultant
      imbalance blunts growth, and may limit the benefits of therapies designed to
      protect and repair dystrophic muscles. 

PMID- 24586654
TI  - Systems genetics of liver fibrosis: identification of fibrogenic and expression
      quantitative trait loci in the BXD murine reference population.
AB  - The progression of liver fibrosis in response to chronic injury varies
      considerably among individual patients. The underlying genetics is highly complex
      due to large numbers of potential genes, environmental factors and cell types
      involved. Here, we provide the first toxicogenomic analysis of liver fibrosis
      induced by carbon tetrachloride in the murine 'genetic reference panel' of
      recombinant inbred BXD lines. Our aim was to define the core of risk genes and
      gene interaction networks that control fibrosis progression. Liver fibrosis
      phenotypes and gene expression profiles were determined in 35 BXD lines.
      Quantitative trait locus (QTL) analysis identified seven genomic loci influencing
      fibrosis phenotypes (pQTLs) with genome-wide significance on chromosomes 4, 5, 7,
      12, and 17. Stepwise refinement was based on expression QTL mapping with
      stringent selection criteria, reducing the number of 1,351 candidate genes
      located in the pQTLs to a final list of 11 cis-regulated genes. Our findings
      demonstrate that the BXD reference population represents a powerful experimental
      resource for shortlisting the genes within a regulatory network that determine
      the liver's vulnerability to chronic injury. 

PMID- 24586655
TI  - A pilot study exploring the use of breath analysis to differentiate healthy
      cattle from cattle experimentally infected with Mycobacterium bovis.
AB  - Bovine tuberculosis, caused by Mycobacterium bovis, is a zoonotic disease of
      international public health importance. Ante-mortem surveillance is essential for
      control; however, current surveillance tests are hampered by limitations
      affecting ease of use or quality of results. There is an emerging interest in
      human and veterinary medicine in diagnosing disease via identification of
      volatile organic compounds produced by pathogens and host-pathogen interactions.
      The objective of this pilot study was to explore application of existing human
      breath collection and analysis methodologies to cattle as a means to identify M.
      bovis infection through detection of unique volatile organic compounds or changes
      in the volatile organic compound profiles present in breath. Breath samples from
      23 male Holstein calves (7 non-infected and 16 M. bovis-infected) were collected
      onto commercially available sorbent cartridges using a mask system at 90 days
      post-inoculation with M. bovis. Samples were analyzed using gas chromatography
      mass spectrometry, and chromatographic data were analyzed using standard
      analytical chemical and metabolomic analyses, principle components analysis, and
      a linear discriminant algorithm. The findings provide proof of concept that
      breath-derived volatile organic compound analysis can be used to differentiate
      between healthy and M. bovis-infected cattle. 

PMID- 24586656
TI  - Prevalence of premorbid metabolic syndrome in Spanish adult workers using IDF and
      ATPIII diagnostic criteria: relationship with cardiovascular risk factors.
AB  - BACKGROUND: Metabolic Syndrome (MetS) is a complex disorder defined as a cluster
      of interconnected risk factors such as hypertension, dyslipidemia, obesity and
      high blood glucose levels. Premorbid metabolic syndrome (PMetS) is defined by
      excluding patients with previously diagnosed cardiovascular disease or diabetes
      mellitus from those suffering MetS. We aimed to determine the prevalence of PMetS
      in a working population, and to analyse the relationship between the diagnostic
      criteria of the International Diabetes Federation (IDF) and of the National
      Cholesterol Education Program Adult Treatment Panel III (ATPIII). The
      relationship between the presence of PMetS and cardiovascular risk factors was
      also analysed. RESEARCH METHODOLOGY/FINDINGS: A cross-sectional study was
      conducted in 24,529 male and 18,736 female Spanish (white western European) adult
      workers (20-65 years) randomly selected during their work health periodic
      examinations. Anthropometrics, blood pressure and serum parameters were measured.
      The presence of MetS and PMetS was ascertained using ATPIII and IDF criteria.
      Cardiovascular risk was determined using the Framingham-REGICOR equation. The
      results showed MetS had an adjusted global prevalence of 12.39% using ATPIII
      criteria and 16.46% using IDF criteria. The prevalence of PMetS was slightly
      lower (11.21% using ATPIII criteria and 14.72% using IDF criteria). Prevalence in
      males was always higher than in females. Participants with PMetS displayed higher
      values of BMI, waist circumference, blood pressure, glucose and triglycerides,
      and lower HDL-cholesterol levels. Logistic regression models reported lower PMetS
      risk for females, non-obese subjects, non-smokers and younger participants.
      Cardiovascular risk determined with Framingham-REGICOR was higher in participants
      with PMetS. CONCLUSIONS: PMetS could be a reliable tool for the early
      identification of apparently healthy individuals who have a significant risk for
      developing cardiovascular events and type 2 diabetes.

PMID- 24586657
TI  - Dynamic positron emission tomography image restoration via a kinetics-induced
      bilateral filter.
AB  - Dynamic positron emission tomography (PET) imaging is a powerful tool that
      provides useful quantitative information on physiological and biochemical
      processes. However, low signal-to-noise ratio in short dynamic frames makes
      accurate kinetic parameter estimation from noisy voxel-wise time activity curves
      (TAC) a challenging task. To address this problem, several spatial filters have
      been investigated to reduce the noise of each frame with noticeable gains. These
      filters include the Gaussian filter, bilateral filter, and wavelet-based filter.
      These filters usually consider only the local properties of each frame without
      exploring potential kinetic information from entire frames. Thus, in this work,
      to improve PET parametric imaging accuracy, we present a kinetics-induced
      bilateral filter (KIBF) to reduce the noise of dynamic image frames by
      incorporating the similarity between the voxel-wise TACs using the framework of
      bilateral filter. The aim of the proposed KIBF algorithm is to reduce the noise
      in homogeneous areas while preserving the distinct kinetics of regions of
      interest. Experimental results on digital brain phantom and in vivo rat study
      with typical (18)F-FDG kinetics have shown that the present KIBF algorithm can
      achieve notable gains over other existing algorithms in terms of quantitative
      accuracy measures and visual inspection. 

PMID- 24586658
TI  - Global analysis of lysine acetylation suggests the involvement of protein
      acetylation in diverse biological processes in rice (Oryza sativa).
AB  - Lysine acetylation is a reversible, dynamic protein modification regulated by
      lysine acetyltransferases and deacetylases. Recent advances in high-throughput
      proteomics have greatly contributed to the success of global analysis of lysine
      acetylation. A large number of proteins of diverse biological functions have been
      shown to be acetylated in several reports in human cells, E.coli, and dicot
      plants. However, the extent of lysine acetylation in non-histone proteins remains
      largely unknown in monocots, particularly in the cereal crops. Here we report the
      mass spectrometric examination of lysine acetylation in rice (Oryza sativa). We
      identified 60 lysine acetylated sites on 44 proteins of diverse biological
      functions. Immunoblot studies further validated the presence of a large number of
      acetylated non-histone proteins. Examination of the amino acid composition
      revealed substantial amino acid bias around the acetylation sites and the amino
      acid preference is conserved among different organisms. Gene ontology analysis
      demonstrates that lysine acetylation occurs in diverse cytoplasmic, chloroplast
      and mitochondrial proteins in addition to the histone modifications. Our results
      suggest that lysine acetylation might constitute a regulatory mechanism for many
      proteins, including both histones and non-histone proteins of diverse biological
      functions. 

PMID- 24586659
TI  - Positive regulation of TRAF6-dependent innate immune responses by protein
      phosphatase PP1-gamma.
AB  - Innate immune sensors such as Toll-like receptors (TLRs) differentially utilize
      adaptor proteins and additional molecular mediators to ensure robust and precise
      immune responses to pathogen challenge. Through a gain-of-function genetic
      screen, we identified the gamma catalytic subunit of protein phosphatase 1 (PP1
      gamma) as a positive regulator of MyD88-dependent proinflammatory innate immune
      activation. PP1-gamma physically interacts with the E3 ubiquitin ligase TRAF6,
      and enhances the activity of TRAF6 towards itself and substrates such as
      IKKgamma, whereas enzymatically inactive PP1-gamma represses these events.
      Importantly, these activities were found to be critical for cellular innate
      responses to pathogen challenge and microbial clearance in both mouse macrophages
      and human monocyte lines. These data indicate that PP1-gamma phosphatase activity
      regulates overall TRAF6 E3 ubiquitin ligase function and promotes NF-kappaB
      mediated innate signaling responses. 

PMID- 24586660
TI  - Small molecule inhibitors target the tissue transglutaminase and fibronectin
      interaction.
AB  - Tissue transglutaminase (TG2) mediates protein crosslinking through generation of
      epsilon-(gamma-glutamyl) lysine isopeptide bonds and promotes cell adhesion
      through interaction with fibronectin (FN) and integrins. Cell adhesion to the
      peritoneal matrix regulated by TG2 facilitates ovarian cancer dissemination.
      Therefore, disruption of the TG2-FN complex by small molecules may inhibit cell
      adhesion and metastasis. A novel high throughput screening (HTS) assay based on
      AlphaLISATM technology was developed to measure the formation of a complex
      between His-TG2 and the biotinylated FN fragment that binds TG2 and to discover
      small molecules that inhibit this protein-protein interaction. Several hits were
      identified from 10,000 compounds screened. The top candidates selected based on
      >70% inhibition of the TG2/FN complex formation were confirmed by using ELISA and
      bioassays measuring cell adhesion, migration, invasion, and proliferation. In
      conclusion, the AlphaLISA bead format assay measuring the TG2-FN interaction is
      robust and suitable for HTS of small molecules. One compound identified from the
      screen (TG53) potently inhibited ovarian cancer cell adhesion to FN, cell
      migration, and invasion and could be further developed as a potential inhibitor
      for ovarian cancer dissemination. 

PMID- 24586661
TI  - Increasing prion propensity by hydrophobic insertion.
AB  - Prion formation involves the conversion of proteins from a soluble form into an
      infectious amyloid form. Most yeast prion proteins contain glutamine/asparagine
      rich regions that are responsible for prion aggregation. Prion formation by these
      domains is driven primarily by amino acid composition, not primary sequence, yet
      there is a surprising disconnect between the amino acids thought to have the
      highest aggregation propensity and those that are actually found in yeast prion
      domains. Specifically, a recent mutagenic screen suggested that both aromatic and
      non-aromatic hydrophobic residues strongly promote prion formation. However,
      while aromatic residues are common in yeast prion domains, non-aromatic
      hydrophobic residues are strongly under-represented. Here, we directly test the
      effects of hydrophobic and aromatic residues on prion formation. Remarkably, we
      found that insertion of as few as two hydrophobic residues resulted in a multiple
      orders-of-magnitude increase in prion formation, and significant acceleration of
      in vitro amyloid formation. Thus, insertion or deletion of hydrophobic residues
      provides a simple tool to control the prion activity of a protein. These data,
      combined with bioinformatics analysis, suggest a limit on the number of strongly
      prion-promoting residues tolerated in glutamine/asparagine-rich domains. This
      limit may explain the under-representation of non-aromatic hydrophobic residues
      in yeast prion domains. Prion activity requires not only that a protein be able
      to form prion fibers, but also that these fibers be cleaved to generate new
      independently-segregating aggregates to offset dilution by cell division. Recent
      studies suggest that aromatic residues, but not non-aromatic hydrophobic
      residues, support the fiber cleavage step. Therefore, we propose that while both
      aromatic and non-aromatic hydrophobic residues promote prion formation, aromatic
      residues are favored in yeast prion domains because they serve a dual function,
      promoting both prion formation and chaperone-dependent prion propagation. 

PMID- 24586662
TI  - Association between soy isoflavone intake and breast cancer risk for pre- and
      post-menopausal women: a meta-analysis of epidemiological studies.
AB  - BACKGROUND: Conclusions drawn from meta-analyses on the association between soy
      isoflavone intake and breast cancer risk for pre- and post-menopausal women are
      not fully consistent. These meta-analyses did not explore the influence of
      different study designs on the pooled results on the basis of distinguishing
      between pre- and post-menopausal women. METHODOLOGY AND PRINCIPAL FINDINGS: We
      performed a meta-analysis of 35 studies which reported results of association
      between soy isoflavone intake and breast cancer risk for pre- and/or post
      menopausal women, calculated pooled odds ratios and their 95% confidence
      intervals of pre- and post-menopausal women respectively, and further explored
      soy isoflavone-breast cancer association on the basis of considering different
      study regions and designs. Summary results suggested that soy isoflavone intake
      has a protective effect against breast cancer for both pre- and post-menopausal
      women. However, they are influenced by study design and region. Pooled ORs of
      studies carried out in Asian countries suggested that soy isoflavone's protective
      effect exist in both pre- and post-menopausal women (OR = 0.59, 95%CI: 0.48-0.69
      for premenopausal women; OR = 0.59, 95%CI: 0.44-0.74 for postmenopausal women).
      However, there are some differences between the results pooled from different
      study designs for women in Asian countries (test for consistency, P = 0.04).
      Pooled OR of studies on postmenopausal women in Western countries suggested that
      soy isoflavone intake has a marginally significant protective effect (OR = 0.92;
      95%CI: 0.83 ~ 1.00), but further analyses stratifying by study design found no
      statistically significant association. CONCLUSIONS: We meta-analyzed more and
      newer research results, and separated women according to menopausal status to
      explore soy isoflavone-breast cancer association. We founded that soy isoflavone
      intake could lower the risk of breast cancer for both pre- and post-menopausal
      women in Asian countries. However, for women in Western countries, pre- or post
      menopausal, there is no evidence to suggest an association between intake of soy
      isoflavone and breast cancer.

PMID- 24586663
TI  - Phylogeny and molecular evolution analysis of PIN-FORMED 1 in angiosperm.
AB  - PIN-FORMED 1 (PIN1) is an important secondary transporter and determines the
      direction of intercellular auxin flow. As PIN1 performs the conserved function of
      auxin transport, it is expected that the sequence and structure of PIN1 is
      conserved. Therefore, we hypothesized that PIN1 evolve under pervasive purifying
      selection in the protein-coding sequences in angiosperm. To test this hypothesis,
      we performed detailed evolutionary analyses of 67 PIN1 sequences from 35
      angiosperm species. We found that the PIN1 sequences are highly conserved within
      their transmembrane regions, part of their hydrophilic regions. We also found
      that there are two or more PIN1 copies in some of these angiosperm species. PIN1
      sequences from Poaceae and Brassicaceae are representative of the modern clade.
      We identified 12 highly conserved motifs and a significant number of family
      specific sites within these motifs. One family-specific site within Motif 11
      shows a different residue between monocots and dicots, and is functionally
      critical for the polarity of PIN1. Likewise, the function of PIN1 appears to be
      different between monocots and dicots since the phenotype associated with PIN1
      overexpression is opposite between Arabidopsis and rice. The evolution of
      angiosperm PIN1 protein-coding sequences appears to have been primarily driven by
      purifying selection, but traces of positive selection associated with sequences
      from certain families also seem to be present. We verified this observation by
      calculating the numbers of non-synonymous and synonymous changes on each branch
      of a phylogenetic tree. Our results indicate that the evolution of angiosperm
      PIN1 sequences involve strong purifying selection. In addition, our results
      suggest that the conserved sequences of PIN1 derive from a combination of the
      family-specific site variations and conserved motifs during their unique
      evolutionary processes, which is critical for the functional integrity and
      stability of these auxin transporters, especially in new species. Finally,
      functional difference of PIN1 is likely to be present in angiosperm because the
      positive selection is occurred in one branch of Poaceae. 

PMID- 24586664
TI  - Impact of a community based implementation of REACH II program for caregivers of
      Alzheimer's patients.
AB  - BACKGROUND: In 2009 an estimated 5.3 million people in the United States were
      afflicted with Alzheimer's disease, a degenerative form of dementia. The impact
      of this disease is not limited to the patient but also has significant impact on
      the lives and health of their family caregivers. The Resources for Enhancing
      Alzheimer's Caregiver Health (REACH II) program was developed and tested in
      clinical studies. The REACH II program is now being delivered by community
      agencies in several locations. This study examines the impact of the REACH II
      program on caregiver lives and health in a city in north Texas. STUDY DESIGN:
      Family caregivers of Alzheimer's patients were assessed using an instrument
      covering the multi-item domains of Caregiver Burden, Depression, Self-Care, and
      Social Support upon enrollment in the program and at the completion of the 6
      month intervention. The domain scores were analyzed using a multivariate paired t
      test and Bonferroni confidence interval for the differences in pre- and post
      service domain scores. RESULTS: A total of 494 families were enrolled in the
      program during the period January 1, 2011 through June 30, 2012. Of these
      families 177 completed the 6 month program and have pre - and post service domain
      scores. The median age for the caregivers was 62 years. The domain scores for
      Depression and Caregiver Burden demonstrated statistically significant
      improvements upon program completion. CONCLUSION: The REACH II intervention was
      successfully implemented by a community agency with comparable impacts to those
      of the clinical trial warranting wider scale implementation.

PMID- 24586665
TI  - Characteristics of HIV-1 natural drug resistance-associated mutations in former
      paid blood donors in Henan Province, China.
AB  - BACKGROUND: Natural drug resistance is a major cause of antiviral treatment
      failure. The characteristics of HIV-1 natural drug resistance-associated
      mutations in former paid blood donors in Henan Province remain unclear. METHODS:
      One hundred and fifty HIV-1-positive plasma samples were collected. Plasma viral
      RNA was extracted for pol gene amplification and sequencing. The sequencing
      results were submitted to the HIV-1 drug resistance database for drug-resistance
      analysis. RESULTS: The rates of natural drug resistance and resistance-associated
      mutations were 17.7% (19/107) and 40.2% (43/107), respectively. The rates of PI
      major, PI minor, NRTI, and NNRTI mutations were: 0, 30.8% (33/107), 10.3%
      (11/107), and 18.7% (20/107), respectively. Nine cases (8.4%) had both NRTI and
      NNRTI resistance-associated mutations. Seven cases (6.5%) had PI minor, NRTI and
      NNRTI resistance-associated mutations. NNRTI resistance was the most serious,
      followed by NRTI resistance and PI resistance. Polymorphism mutation sites with
      mutation rates in the protease region higher than 60.0% were: L63A/P/S/T 89.7%,
      V77I 82.2%, I72E/M/K/T/V 80.4%, I93L 75.7%, and E35D 72.9%. Polymorphism mutation
      sites with mutation rates in the RT region higher than 60.0% were:
      I135A/L/M/R/T/V 93.5%, T200A/E/I/P/V 89.7%, Q278E/K/N/T 88.8%, S162C/Y 82.2%, and
      K277R/S 66.4%. The distribution of 107 gene sequences was scattered, with some
      drug-resistant strains grouped in the same cluster. CONCLUSION: The natural drug
      resistance mutation rate of HIV-1 in former paid blood donors in Henan Province
      was 17.7%, with NNRTI resistance the most serious. The distribution of drug
      resistant strains was scattered, with some correlations found in certain
      resistance loci.

PMID- 24586666
TI  - Store-operated Ca2+ entry (SOCE) regulates melanoma proliferation and cell
      migration.
AB  - Store-operated Ca(2+) entry (SOCE) is a major mechanism of Ca(2) (+) import from
      extracellular to intracellular space, involving detection of Ca(2+) store
      depletion in endoplasmic reticulum (ER) by stromal interaction molecule (STIM)
      proteins, which then translocate to plasma membrane and activate Orai Ca(2+)
      channels there. We found that STIM1 and Orai1 isoforms were abundantly expressed
      in human melanoma tissues and multiple melanoma/melanocyte cell lines. We
      confirmed that these cell lines exhibited SOCE, which was inhibited by knockdown
      of STIM1 or Orai1, or by a pharmacological SOCE inhibitor. Inhibition of SOCE
      suppressed melanoma cell proliferation and migration/metastasis. Induction of
      SOCE was associated with activation of extracellular-signal-regulated kinase
      (ERK), and was inhibited by inhibitors of calmodulin kinase II (CaMKII) or Raf-1,
      suggesting that SOCE-mediated cellular functions are controlled via the
      CaMKII/Raf-1/ERK signaling pathway. Our findings indicate that SOCE contributes
      to melanoma progression, and therefore may be a new potential target for
      treatment of melanoma, irrespective of whether or not Braf mutation is present. 

PMID- 24586667
TI  - Real-time electrochemical recording of dopamine release under optogenetic
      stimulation.
AB  - Dopaminergic PC12 cells can synthesize and release dopamine, providing a good
      cellular model for investigating dopamine regulation. Optogenetic stimulation of
      channelrhodopsin-2 provides high spatial and temporal precision for selective
      stimulation as a powerful neuromodulation tool for neuroscience studies. The aim
      of this study is to measure dopamine release from dopaminergic PC12 cells under
      optogenetic stimulation using electrochemical recording of self-assembled
      monolayers modified microelectrode with amperometric measurement in real time.
      The activation of PC12 cells under various optogenetic stimulation schemes are
      characterized by measuring single-cell Ca(2+) imaging. After 10 seconds of
      optogenetic stimulation, the evoked intracellular Ca(2+) level and dopamine
      current of channelrhodopsin-2-transfected PC12 cells were 1.6- and 3.5-fold
      higher than those of the control cells. The optogenetic stimulation effects on
      Ca(2+) influx and dopamine release were 81% and 63% inhibition by using a Ca(2+)
      channel antagonist Nifedipine. The results indicate that optogenetic stimulation
      can evoke voltage-gated Ca(2+) channel-dependent dopamine exocytosis from PC12
      cells in a cell specific, temporally precise and dose-dependent manner. This
      proposed dopamine recording system can be developed to be a good cell model for
      dopamine regulation and drug screening in vitro, or dopaminergic cell
      implantation therapy in vivo using optogenetic stimulation in a precise and
      convenient way. 

PMID- 24586668
TI  - Diurnal and seasonal change in stem respiration of Larix principis-rupprechtii
      trees, northern China.
AB  - Stem respiration is a critical and uncertain component of ecosystem carbon cycle.
      Few studies reported diurnal change in stem respiration as well as its linkage
      with climate. In this study, we investigated the diurnal and seasonal change in
      stem respiration and its linkage with environmental factors, in larch plantations
      of northern China from 2010 to 2012. The stem respiration per unit surface area
      (RS) showed clear diurnal cycles, ranging from 1.65+/-0.10 to 2.69+/-0.15 umol m(
      2) s(-1), increased after 6?00, peaked at 15?00 and then decreased. Both stem
      temperature and air temperature show similar diurnal pattern, while the diurnal
      pattern of air relative humidity is just the opposite to Rs. Similar to the
      diurnal cycles, seasonal change in RS followed the pattern of stem temperature.
      RS increased from May (1.28+/-0.07 umol m(-2) s(-1)) when the stem temperature
      was relatively low and peaked in July (3.02+/-0.10 umol m(-2) s(-1)) when the
      stem temperature was also the highest. Further regression analyses show that RS
      exponentially increases with increasing temperature, and the Q10 of Rs at mid
      daytime (1.97+/-0.17 at 12?00 and 1.96+/-0.10 at 15?00) is significantly lower
      than that of mid nighttime (2.60+/-0.14 at 00?00 and 2.71+/-0.25 at 03?00) Q10.
      This result not only implies that Rs is more sensitive to night than day warming,
      but also highlights that temperature responses of Rs estimated by only daytime
      measurement can lead to underestimated stem respiration increase under global
      warming, especially considering that temperature increase is faster during
      nighttime. 

PMID- 24586669
TI  - Interactions between a sap beetle, sabal palm, scale insect, filamentous fungi
      and yeast, with discovery of potential antifungal compounds.
AB  - The multi-trophic relationship between insects, yeast, and filamentous fungi is
      reported on sabal palm (Sabal palmetto (Walter) Lodd. ex Schult. & Schult. f.).
      Gut content analyses and observations of adult and larval feeding of the sap
      beetle Brachypeplus glaber LeConte indicate that niche partitioning of fungal
      food substrata occurs between adults and larvae. This is the first report of
      specific mycophagous niche partitioning among beetle life stages based on gut
      content analyses. Fungi isolated from the beetle gut of adults, larvae, and pupae
      include species of Fusarium Link, Cladosporium Link, and Penicillium Link, which
      were differentially ingested by larvae and adults; Fusarium solani and
      Penicillium species in larvae, whereas F. oxysoproum, F. verticillioides, and
      Cladosporium in adults. These data indicate the first species-level host data for
      Brachypeplus Erichson species. Fusarium proliferatum (Matsush.) Nirenberg was the
      most commonly occurring fungal gut component, being isolated from the palm as
      well as gut of larvae, pupae, and adults; representing a commonly shared food
      resource. One species of yeast, Meyerozyma caribbica (Vaughan-Mart. et al.)
      Kurtzman & Suzuki (basionym = Pichia caribbica), was isolated from all life
      stages and is likely responsible for anti-fungal properties observed in the pupae
      and represents a promising source of antifungal compounds; rearing and diagnostic
      protocols are provided to aid biomedical researchers. Feeding and cleaning
      behaviors are documented using time-lapse video-micrography, and discussed in a
      behavioral and functional morphological context. Adults spent long periods
      feeding, often >1/3 of the two-hour observation period. A generic adult body
      posture was observed during feeding, and included substrate antennation before
      and after ingestion. Adult grooming behaviors were manifested in distinct
      antennal and tarsal cleaning mechanisms. Larval behaviors were different from
      adults, and larvae feeding on Fusarium fungi immediately ceased all subsequent
      feeding. This is the first ethogram for any adult or larval sap beetle.

PMID- 24586670
TI  - An assessment of the long-term effects of simulated microgravity on cranial
      neural crest cells in zebrafish embryos with a focus on the adult skeleton.
AB  - It is becoming increasingly important to address the long-term effects of
      exposure to simulated microgravity as the potential for space tourism and life in
      space become prominent topics amongst the World's governments. There are several
      studies examining the effects of exposure to simulated microgravity on various
      developmental systems and in various organisms; however, few examine the effects
      beyond the juvenile stages. In this study, we expose zebrafish embryos to
      simulated microgravity starting at key stages associated with cranial neural
      crest cell migration. We then analyzed the skeletons of adult fish. Gross
      observations and morphometric analyses show that exposure to simulated
      microgravity results in stunted growth, reduced ossification and severe
      distortion of some skeletal elements. Additionally, we investigated the effects
      on the juvenile skull and body pigmentation. This study determines for the first
      time the long-term effects of embryonic exposure to simulated microgravity on the
      developing skull and highlights the importance of studies investigating the
      effects of altered gravitational forces. 

PMID- 24586671
TI  - Meta-analysis of pathway enrichment: combining independent and dependent omics
      data sets.
AB  - A major challenge in current systems biology is the combination and integrative
      analysis of large data sets obtained from different high-throughput omics
      platforms, such as mass spectrometry based Metabolomics and Proteomics or DNA
      microarray or RNA-seq-based Transcriptomics. Especially in the case of non
      targeted Metabolomics experiments, where it is often impossible to unambiguously
      map ion features from mass spectrometry analysis to metabolites, the integration
      of more reliable omics technologies is highly desirable. A popular method for the
      knowledge-based interpretation of single data sets is the (Gene) Set Enrichment
      Analysis. In order to combine the results from different analyses, we introduce a
      methodical framework for the meta-analysis of p-values obtained from Pathway
      Enrichment Analysis (Set Enrichment Analysis based on pathways) of multiple
      dependent or independent data sets from different omics platforms. For dependent
      data sets, e.g. obtained from the same biological samples, the framework utilizes
      a covariance estimation procedure based on the nonsignificant pathways in single
      data set enrichment analysis. The framework is evaluated and applied in the joint
      analysis of Metabolomics mass spectrometry and Transcriptomics DNA microarray
      data in the context of plant wounding. In extensive studies of simulated data set
      dependence, the introduced correlation could be fully reconstructed by means of
      the covariance estimation based on pathway enrichment. By restricting the range
      of p-values of pathways considered in the estimation, the overestimation of
      correlation, which is introduced by the significant pathways, could be reduced.
      When applying the proposed methods to the real data sets, the meta-analysis was
      shown not only to be a powerful tool to investigate the correlation between
      different data sets and summarize the results of multiple analyses but also to
      distinguish experiment-specific key pathways. 

PMID- 24586672
TI  - Prevalence of and associated factors for adult attention deficit hyperactivity
      disorder in young Swiss men.
AB  - OBJECTIVE: The present study aimed to measure the prevalence of adult attention
      deficit hyperactivity disorder (ADHD) in a large, representative sample of young
      Swiss men and to assess factors associated with this disorder. METHODS: Our
      sample consisted of 5656 Swiss men (mean age 20 years) who participated in the
      Cohort Study on Substance Use Risk Factors (C-SURF). ADHD was assessed with the
      World Health Organization (WHO) adult ADHD Self Report Screener (ASRS). Logistic
      regression analyses were conducted to assess the association between ADHD and
      several socio-demographic, clinical and familial factors. RESULTS: The prevalence
      of ADHD was 4.0%, being higher in older and French-speaking conscripts. A higher
      prevalence also was identified among men whose mothers had completed primary or
      high school/university and those with a family history of alcohol or psychiatric
      problems. Additionally, adults with ADHD demonstrated impairment in their
      professional life, as well as considerable mental health impairment. CONCLUSION:
      Our results demonstrate that ADHD is common among young Swiss men. The
      impairments in function and mental health we observed highlight the need for
      further support and interventions to reduce burden in affected individuals.
      Interventions that incorporate the whole family also seem crucial.

PMID- 24586673
TI  - Absence of effect of menopause status at initiation of first-line antiretroviral
      therapy on immunologic or virologic responses: a cohort study from Rio de
      Janeiro, Brazil.
AB  - OBJECTIVE: To compare the effectiveness of first-line combination antiretroviral
      therapy (cART) between premenopausal and postmenopausal women. METHODS: ART-naive
      women initiating cART between January 2000/June 2010 at the Instituto de Pesquisa
      Clinica Evandro Chagas Cohort were studied. Women were defined as postmenopausal
      after 12 consecutive months of amenorrhea. CD4 cell counts and HIV-1 RNA viral
      load (VL) measurements were compared between pre- and postmenopausal at 6, 12 and
      24 months after cART initiation. Women who modified/discontinued a drug class or
      died due to an AIDS defining illness were classified as ART-failures. Variables
      were compared using Wilcoxon test, chi2 or Fisher's exact test. The odds of cART
      effectiveness (VL<400 copies/mL and/or no need to change cART) were compared
      using logistic regression. Linear model was used to access relationship between
      CD4 change and menopause. RESULTS: Among 383 women, 328 (85%) were premenopausal
      and 55 (15%) postmenopausal. Median pre cART CD4 counts were 231 and 208
      cells/mm(3) (p = 0.14) in pre- and postmenopausal women, respectively. No
      difference in the median pre cART VL was found (both 4.8 copies/mL). Median CD4
      changes were similar at 6 and 12 months. At 24 months after cART initiation, CD4
      changes among postmenopausal women were significantly lower among premenopausal
      women (p = 0.01). When the analysis was restricted to women with VL<400
      copies/mL, no statistical difference was observed. Overall, 63.7% achieved cART
      effectiveness at 24 months without differences between groups at 6, 12 and 24
      months. CONCLUSION: Menopause status at the time of first-line cART initiation
      does not impact CD4 cell changes at 24 months among women with a virologic
      response. No relationship between menopause status and virologic response was
      observed.

PMID- 24586674
TI  - Exposure to MIV-150 from a high-dose intravaginal ring results in limited
      emergence of drug resistance mutations in SHIV-RT infected rhesus macaques.
AB  - When microbicides used for HIV prevention contain antiretroviral drugs, there is
      concern for the potential emergence of drug-resistant HIV following use in
      infected individuals who are either unaware of their HIV infection status or who
      are aware but still choose to use the microbicide. Resistant virus could
      ultimately impact their responsiveness to treatment and/or result in subsequent
      transmission of drug-resistant virus. We tested whether drug resistance mutations
      (DRMs) would emerge in macaques infected with simian immunodeficiency virus
      expressing HIV reverse transcriptase (SHIV-RT) after sustained exposure to the
      potent non-nucleoside reverse transcriptase inhibitor (NNRTI) MIV-150 delivered
      via an intravaginal ring (IVR). We first treated 4 SHIV-RT-infected animals with
      daily intramuscular injections of MIV-150 over two 21 day (d) intervals separated
      by a 7 d drug hiatus. In all 4 animals, NNRTI DRMs (single and combinations) were
      detected within 14 d and expanded in proportion and diversity with time. Knowing
      that we could detect in vivo emergence of NNRTI DRMs in response to MIV-150, we
      then tested whether a high-dose MIV-150 IVR (loaded with >10 times the amount
      being used in a combination microbicide IVR in development) would select for
      resistance in 6 infected animals, modeling use of this prevention method by an
      HIV-infected woman. We previously demonstrated that this MIV-150 IVR provides
      significant protection against vaginal SHIV-RT challenge. Wearing the MIV-150 IVR
      for 56 d led to only 2 single DRMs in 2 of 6 animals (430 RT sequences analyzed
      total, 0.46%) from plasma and lymph nodes despite MIV-150 persisting in the
      plasma, vaginal fluids, and genital tissues. Only wild type virus sequences were
      detected in the genital tissues. These findings indicate a low probability for
      the emergence of DRMs after topical MIV-150 exposure and support the advancement
      of MIV-150-containing microbicides. 

PMID- 24586675
TI  - Feasibility of decentralised deployment of Xpert MTB/RIF test at lower level of
      health system in India.
AB  - BACKGROUND: Xpert MTB/RIF is an automated cartridge-based nucleic acid
      amplification test that has demonstrated its potential to detect tuberculosis and
      rifampicin resistance with high accuracy. To assist scale-up decisions in India,
      a feasibility assessment of Xpert MTB/RIF implementation was conducted within
      microscopy centres of 18 RNTCP TB units. METHODS: As part of programme-based
      demonstration of Xpert MTB/RIF implementation, we recorded and analysed
      association between key implementation factors and the ability of test to produce
      valid results. Factors contributing to test failures were analysed from GeneXpert
      software data which provides 'failure codes' and causes for test failures.
      RESULTS: From March'12 to January'13, total 40,035 suspects were tested by Xpert
      MTB/RIF, and 39,680 (99.1%) received valid results (Cumulative: 37157 (92.8%) on
      first attempt, 39410 (98.4%) on second attempt, 39637 (99.0%) on third attempt
      and 39680 (99.1%) on more attempts). Overall initial test failure was 2,878 (7.2%
      (4%-17%)); of these, 2,594 (90.1%) were re-tested and produced valid results.
      Most frequent reason of test failure was inadequate sample processing or
      equipment malfunction (3.9%). Other reasons included power failure (1.1%),
      cartridge integrity/component failure (0.8%), device-computer communication error
      (0.5%), and temperature-related errors (0.08%). Significant variation was
      observed in failure rates both across instruments and over time; furthermore,
      substantial variation was observed in failure rate in two cartridges lots.
      CONCLUSION: Installation required minimal infrastructure modifications and
      concerns about adequacy of human resources under public sector facilities and
      temperature extremes proved unfounded. Under routine conditions, Xpert MTB/RIF
      provided 99.1% valid results in TB suspects with low overall failure rates (7.2%
      initial failure, 0.9% final failure); devices provided valuable real-time
      feedback on reasons for test failure, which were used for rapid corrective
      action. High modular replacement (32%) and inter-lot cartridge performance
      variation remain sources of concern, and warrant close monitoring of failure
      rates as a key quality indicator.

PMID- 24586676
TI  - GSTT1 deletion is related to polycyclic aromatic hydrocarbons-induced DNA damage
      and lymphoma progression.
AB  - The interrelationship between genetic susceptibility and carcinogenic exposure is
      important in cancer development. Polymorphisms in detoxification enzymes of the
      glutathione-S-transferases (GST) family are associated with an increased
      incidence of lymphoma. Here we investigated the molecular connection of the
      genetic polymorphism of GSTT1 to the response of lymphocytes to polycyclic
      aromatic hydrocarbons (PAH). In neoplastic situation, GSTT1 deletions were more
      frequently observed in lymphoma patients (54.9%) than in normal controls (42.0%,
      P = 0.009), resulting in an increased risk for lymphoma in individuals with GSTT1
      null genotype (Odds ratio = 1.698, 95% confidence interval = 1.145-2.518). GSTT1
      gene and protein expression were accordingly decreased in GSTT1-deleting
      patients, consistent with activated profile of cell cycle regulation genes.
      Mimicking environmental exposure using long-term repeat culture with low-dose PAH
      metabolite Hydroquinone, malignant B- and T-lymphocytes presented increased DNA
      damage, pCHK1/MYC expression and cell proliferation, which were counteracted by
      ectopic expression of GSTT1. Moreover, GSTT1 expression retarded xenograft tumor
      formation of Hydroquinone-treated lymphoma cells in nude mice. In non-neoplastic
      situation, when zebrafish was exposed to PAH Benzo(a)pyrene, molecular silencing
      of gstt1 enhanced the proliferation of normal lymphocytes and upregulated myca
      expression. Collectively, these findings suggested that GSTT1 deletion is related
      to genetic predisposition to lymphoma, particularly interacting with
      environmental pollutants containing PAH.

PMID- 24586677
TI  - Massage therapy for fibromyalgia: a systematic review and meta-analysis of
      randomized controlled trials.
AB  - BACKGROUND: Although some studies evaluated the effectiveness of massage therapy
      for fibromyalgia (FM), the role of massage therapy in the management of FM
      remained controversial. OBJECTIVE: The purpose of this systematic review is to
      evaluate the evidence of massage therapy for patients with FM. METHODS:
      Electronic databases (up to June 2013) were searched to identify relevant
      studies. The main outcome measures were pain, anxiety, depression, and sleep
      disturbance. Two reviewers independently abstracted data and appraised risk of
      bias. The risk of bias of eligible studies was assessed based on Cochrane tools.
      Standardised mean difference (SMD) and 95% confidence intervals (CI) were
      calculated by more conservative random-effects model. And heterogeneity was
      assessed based on the I(2) statistic. RESULTS: Nine randomized controlled trials
      involving 404 patients met the inclusion criteria. The meta-analyses showed that
      massage therapy with duration >= 5 weeks significantly improved pain (SMD, 0.62;
      95% CI 0.05 to 1.20; p = 0.03), anxiety (SMD, 0.44; 95% CI 0.09 to 0.78; p =
      0.01), and depression (SMD, 0.49; 95% CI 0.15 to 0.84; p = 0.005) in patients
      with FM, but not on sleep disturbance (SMD, 0.19; 95% CI -0.38 to 0.75; p =
      0.52). CONCLUSION: Massage therapy with duration >= 5 weeks had beneficial
      immediate effects on improving pain, anxiety, and depression in patients with FM.
      Massage therapy should be one of the viable complementary and alternative
      treatments for FM. However, given fewer eligible studies in subgroup meta
      analyses and no evidence on follow-up effects, large-scale randomized controlled
      trials with long follow-up are warrant to confirm the current findings.

PMID- 24586678
TI  - Separately or combined, LukG/LukH is functionally unique compared to other
      staphylococcal bicomponent leukotoxins.
AB  - Staphylococcus aureus is a major human pathogen that elaborates several
      exotoxins. Among these are the bicomponent leukotoxins (BCLs), which include
      gamma-hemolysin, Panton-Valentine leukocidin (PVL), and LukDE. The toxin
      components are classified as either F or S proteins, which are secreted
      individually and assemble on cell surfaces to form hetero-oligomeric pores
      resulting in lysis of PMNs and/or erythrocytes. F and S proteins of gamma
      hemolysin, PVL and LukDE have ~ 70% sequence homology within the same class and
      several heterologous combinations of F and S members from these three bicomponent
      toxin groups are functional. Recently, an additional BCL pair, LukGH (also called
      LukAB) that has only 30% homology to gamma-hemolysin, PVL and LukDE, has been
      characterized from S. aureus. Our results showed that LukGH was more cytotoxic to
      human PMNs than PVL. However, LukGH-induced calcium ion influx in PMNs was
      markedly attenuated and slower than that induced by PVL and other staphylococcal
      BCLs. In contrast to other heterologous BCL combinations, LukG in combination
      with heterologous S components, and LukH in combination with heterologous F
      components did not induce calcium ion entry or cell lysis in human PMNs or rabbit
      erythrocytes. Like PVL, LukGH induced IL-8 production by PMNs. While individual
      components LukG and LukH had no cytolytic or calcium influx activity, they each
      induced high levels of IL-8 transcription and secretion. IL-8 production induced
      by LukG or LukH was dependent on NF-kappaB. Therefore, our results indicate LukGH
      differs functionally from other staphylococcal BCLs.

PMID- 24586679
TI  - Healthy animals, healthy people: zoonosis risk from animal contact in pet shops,
      a systematic review of the literature.
AB  - BACKGROUND: Around 67 million pets are owned by households in the United Kingdom,
      and an increasing number of these are exotic animals. Approximately a third of
      pets are purchased through retail outlets or direct from breeders. A wide range
      of infections can be associated with companion animals. OBJECTIVES: This study
      uses a systematic literature review to describe the transmission of zoonotic
      disease in humans associated with a pet shop or other location selling pets
      (incidents of rabies tracebacks and zoonoses from pet food were excluded). DATA
      SOURCES: PubMed and EMBASE. RESULTS: Fifty seven separate case reports or
      incidents were described in the 82 papers that were identified by the systematic
      review. Summary information on each incident is included in this manuscript. The
      infections include bacterial, viral and fungal diseases and range in severity
      from mild to life threatening. Infections associated with birds and rodents were
      the most commonly reported. Over half of the reports describe incidents in the
      Americas, and three of these were outbreaks involving more than 50 cases. Many of
      the incidents identified relate to infections in pet shop employees. LIMITATIONS:
      This review may have been subject to publication bias, where unusual and
      unexpected zoonotic infections may be over-represented in peer-reviewed
      publications. It was also restricted to English-language articles so that
      pathogens that are more common in non-Western countries, or in more exotic
      animals not common in Europe and the Americas, may have been under-represented.
      CONCLUSIONS/IMPLICATIONS: A wide spectrum of zoonotic infections are acquired
      from pet shops. Salmonellosis and psittacosis were the most commonly documented
      diseases, however more unusual infections such as tularemia also appeared in the
      review. Given their potential to spread zoonotic infection, it is important that
      pet shops act to minimise the risk as far as possible.

PMID- 24586680
TI  - Nuclear receptor 4a3 (nr4a3) regulates murine mast cell responses and granule
      content.
AB  - Nuclear receptor 4a3 (Nr4a3) is a transcription factor implicated in various
      settings such as vascular biology and inflammation. We have recently shown that
      mast cells dramatically upregulate Nuclear receptor 4a3 upon activation, and here
      we investigated the functional impact of Nuclear receptor 4a3 on mast cell
      responses. We show that Nuclear receptor 4a3 is involved in the regulation of
      cytokine/chemokine secretion in mast cells following activation via the high
      affinity IgE receptor. Moreover, Nuclear receptor 4a3 negatively affects the
      transcript and protein levels of mast cell tryptase as well as the mast cell's
      responsiveness to allergen. Together, these findings identify Nuclear receptor
      4a3 as a novel regulator of mast cell function. 

PMID- 24586681
TI  - WXG100 protein superfamily consists of three subfamilies and exhibits an alpha
      helical C-terminal conserved residue pattern.
AB  - Members of the WXG100 protein superfamily form homo- or heterodimeric complexes.
      The most studied proteins among them are the secreted T-cell antigens CFP-10 (10
      kDa culture filtrate protein, EsxB) and ESAT-6 (6 kDa early secreted antigen
      target, EsxA) from Mycobacterium tuberculosis. They are encoded on an operon
      within a gene cluster, named as ESX-1, that encodes for the Type VII secretion
      system (T7SS). WXG100 proteins are secreted in a full-length form and it is known
      that they adopt a four-helix bundle structure. In the current work we discuss the
      evolutionary relationship between the homo- and heterodimeric WXG100 proteins,
      the basis of the oligomeric state and the key structural features of the
      conserved sequence pattern of WXG100 proteins. We performed an iterative
      bioinformatics analysis of the WXG100 protein superfamily and correlated this
      with the atomic structures of the representative WXG100 proteins. We find,
      firstly, that the WXG100 protein superfamily consists of three subfamilies: CFP
      10-, ESAT-6- and sagEsxA-like proteins (EsxA proteins similar to that of
      Streptococcus agalactiae). Secondly, that the heterodimeric complexes probably
      evolved from a homodimeric precursor. Thirdly, that the genes of hetero-dimeric
      WXG100 proteins are always encoded in bi-cistronic operons and finally, by
      combining the sequence alignments with the X-ray data we identify a conserved C
      terminal sequence pattern. The side chains of these conserved residues decorate
      the same side of the C-terminal alpha-helix and therefore form a distinct
      surface. Our results lead to a putatively extended T7SS secretion signal which
      combines two reported T7SS recognition characteristics: Firstly that the T7SS
      secretion signal is localized at the C-terminus of T7SS substrates and secondly
      that the conserved residues YxxxD/E are essential for T7SS activity. Furthermore,
      we propose that the specific alpha-helical surface formed by the conserved
      sequence pattern including YxxxD/E motif is a key component of T7SS-substrate
      recognition. 

PMID- 24586682
TI  - Self-gated free-breathing 3D coronary CINE imaging with simultaneous water and
      fat visualization.
AB  - The aim of this study was to develop a novel technique for acquiring 3
      dimensional (3D) coronary CINE magnetic resonance images with both water and fat
      visualization during free breathing and without external respiratory or cardiac
      gating. The implemented multi-echo hybrid 3D radial balanced Steady-State Free
      Precession (SSFP) sequence has an efficient data acquisition and is robust
      against motion. The k-space center along the slice encoding direction was
      repeatedly acquired to derive both respiratory and cardiac self-gating signals
      without an increase in scan time, enabling a free-breathing acquisition. The
      multi-echo acquisition allowed image reconstruction with water-fat separation,
      providing improved visualization of the coronary artery lumen. Ten healthy
      subjects were imaged successfully at 1.5 T, achieving a spatial resolution of 1.0
      * 1.0 * 3.0 mm(3) and scan time of about 5 minutes. The proposed imaging
      technique provided coronary vessel depiction comparable to that obtained with
      conventional breath-hold imaging and navigator gated free-breathing imaging.

PMID- 24586683
TI  - Conservation of eelgrass (Zostera marina) genetic diversity in a mesocosm-based
      restoration experiment.
AB  - Eelgrass (Zostera marina) forms the foundation of an important shallow coastal
      community in protected estuaries and bays. Widespread population declines have
      stimulated restoration efforts, but these have often overlooked the importance of
      maintaining the evolutionary potential of restored populations by minimizing the
      reduction in genetic diversity that typically accompanies restoration. In an
      experiment simulating a small-scale restoration, we tested the effectiveness of a
      buoy-deployed seeding technique to maintain genetic diversity comparable to the
      seed source populations. Seeds from three extant source populations in San
      Francisco Bay were introduced into eighteen flow-through baywater mesocosms.
      Following seedling establishment, we used seven polymorphic microsatellite loci
      to compare genetic diversity indices from 128 shoots to those found in the source
      populations. Importantly, allelic richness and expected heterozygosity were not
      significantly reduced in the mesocosms, which also preserved the strong
      population differentiation present among source populations. However, the
      inbreeding coefficient F IS was elevated in two of the three sets of mesocosms
      when they were grouped according to their source population. This is probably a
      Wahlund effect from confining all half-siblings within each spathe to a single
      mesocosm, elevating F IS when the mesocosms were considered together. The
      conservation of most alleles and preservation of expected heterozygosity suggests
      that this seeding technique is an improvement over whole-shoot transplantation in
      the conservation of genetic diversity in eelgrass restoration efforts. 

PMID- 24586684
TI  - Global meta-analysis of transcriptomics studies.
AB  - Transcriptomics meta-analysis aims at re-using existing data to derive novel
      biological hypotheses, and is motivated by the public availability of a large
      number of independent studies. Current methods are based on breaking down studies
      into multiple comparisons between phenotypes (e.g. disease vs. healthy), based on
      the studies' experimental designs, followed by computing the overlap between the
      resulting differential expression signatures. While useful, in this methodology
      each study yields multiple independent phenotype comparisons, and connections are
      established not between studies, but rather between subsets of the studies
      corresponding to phenotype comparisons. We propose a rank-based statistical meta
      analysis framework that establishes global connections between transcriptomics
      studies without breaking down studies into sets of phenotype comparisons. By
      using a rank product method, our framework extracts global features from each
      study, corresponding to genes that are consistently among the most expressed or
      differentially expressed genes in that study. Those features are then
      statistically modelled via a term-frequency inverse-document frequency (TF-IDF)
      model, which is then used for connecting studies. Our framework is fast and
      parameter-free; when applied to large collections of Homo sapiens and
      Streptococcus pneumoniae transcriptomics studies, it performs better than
      similarity-based approaches in retrieving related studies, using a Medical
      Subject Headings gold standard. Finally, we highlight via case studies how the
      framework can be used to derive novel biological hypotheses regarding related
      studies and the genes that drive those connections. Our proposed statistical
      framework shows that it is possible to perform a meta-analysis of transcriptomics
      studies with arbitrary experimental designs by deriving global expression
      features rather than decomposing studies into multiple phenotype comparisons. 

PMID- 24586685
TI  - A conditioned response as a measure of impulsive-compulsive behaviours in
      Parkinson's disease.
AB  - OBJECTIVES: Parkinson's Disease patients wore a device on the wrist that gave
      reminders to take levodopa and also measured bradykinesia and dyskinesia.
      Consumption of medications was acknowledged by placing the thumb on the device.
      Some patients performed this acknowledgement repeatedly and unconsciously. This
      study examines whether this behaviour reflected increased impulsivity. METHODS
      AND RESULTS: Twenty five participants were selected because they had i) excess
      acknowledgements described above or ii) Impulsive-Compulsive Behaviours or iii)
      neither of these. A blinded assessor applied clinical scales to measure Impulsive
      Compulsive Behaviours, cognition, depression, anxiety and apathy. A Response
      Ratio, representing the number of acknowledgements/number of doses (expressed as
      a percentage) was tightly correlated with ratings of Impulsive-Compulsive
      Behaviours (r2 = 0.79) in 19/25 subjects. Some of these patients had dyskinesia,
      which was higher with extraneous responses than with response indicating
      medication consumption. Six of the 25 subjects had high Impulsive-Compulsive
      Behaviour Scores, higher apathy scores, low levels of dyskinesia and normal
      Response Ratios. Patients without ICB (low RR) also had low dyskinesia levels
      regardless of the relevance of the response. CONCLUSION: An elevated Response
      Ratio is a specific measure of a type of ICB where increased incentive salience
      is attributed to cues by the presence of high striatal dopamine levels,
      manifested by high levels of dyskinesia. This study also points to a second form
      of ICBs which occur in the absence of dyskinesia, has normal Response Ratios and
      higher apathy scores, and may represent prefrontal pathology.

PMID- 24586687
TI  - Gene expression alterations in the cerebellum and granule neurons of Cstb(-/-)
      mouse are associated with early synaptic changes and inflammation.
AB  - Progressive myoclonus epilepsy of Unverricht-Lundborg type (EPM1) is an autosomal
      recessively inherited neurodegenerative disease, manifesting with myoclonus,
      seizures and ataxia, caused by mutations in the cystatin B (CSTB) gene. With the
      aim of understanding the molecular basis of pathogenetic events in EPM1 we
      characterized gene expression changes in the cerebella of pre-symptomatic
      postnatal day 7 (P7) and symptomatic P30 cystatin B -deficient (Cstb(-/-) ) mice,
      a model for the disease, and in cultured Cstb(-/-) cerebellar granule cells using
      a pathway-based approach. Differentially expressed genes in P7 cerebella were
      connected to synaptic function and plasticity, and in cultured cerebellar granule
      cells, to cell cycle, cytoskeleton, and intracellular transport. In particular,
      the gene expression data pinpointed alterations in GABAergic pathway.
      Electrophysiological recordings from Cstb(-/-) cerebellar Purkinje cells revealed
      a shift of the balance towards decreased inhibition, yet the amount of inhibitory
      interneurons was not declined in young animals. Instead, we found diminished
      number of GABAergic terminals and reduced ligand binding to GABAA receptors in
      Cstb(-/-) cerebellum. These results suggest that alterations in GABAergic
      signaling could result in reduced inhibition in Cstb(-/-) cerebellum leading to
      the hyperexcitable phenotype of Cstb(-/-) mice. At P30, the microarray data
      revealed a marked upregulation of immune and defense response genes, compatible
      with the previously reported early glial activation that precedes neuronal
      degeneration. This further implies the role of early-onset neuroinflammation in
      the pathogenesis of EPM1. 

PMID- 24586686
TI  - Parental binge alcohol abuse alters F1 generation hypothalamic gene expression in
      the absence of direct fetal alcohol exposure.
AB  - Adolescent binge alcohol exposure has long-lasting effects on the expression of
      hypothalamic genes that regulate the stress response, even in the absence of
      subsequent adult alcohol exposure. This suggests that alcohol can induce
      permanent gene expression changes, potentially through epigenetic modifications
      to specific genes. Epigenetic modifications can be transmitted to future
      generations therefore, and in these studies we investigated the effects of
      adolescent binge alcohol exposure on hypothalamic gene expression patterns in the
      F1 generation offspring. It has been well documented that maternal alcohol
      exposure during fetal development can have devastating neurological consequences.
      However, less is known about the consequences of maternal and/or paternal alcohol
      exposure outside of the gestational time frame. Here, we exposed adolescent male
      and female rats to a repeated binge EtOH exposure paradigm and then mated them in
      adulthood. Hypothalamic samples were taken from the offspring of these animals at
      postnatal day (PND) 7 and subjected to a genome-wide microarray analysis followed
      by qRT-PCR for selected genes. Importantly, the parents were not intoxicated at
      the time of mating and were not exposed to EtOH at any time during gestation
      therefore the offspring were never directly exposed to EtOH. Our results showed
      that the offspring of alcohol-exposed parents had significant differences
      compared to offspring from alcohol-naive parents. Specifically, major differences
      were observed in the expression of genes that mediate neurogenesis and synaptic
      plasticity during neurodevelopment, genes important for directing chromatin
      remodeling, posttranslational modifications or transcription regulation, as well
      as genes involved in regulation of obesity and reproductive function. These data
      demonstrate that repeated binge alcohol exposure during pubertal development can
      potentially have detrimental effects on future offspring even in the absence of
      direct fetal alcohol exposure. 

PMID- 24586688
TI  - Sinks for inorganic nitrogen deposition in forest ecosystems with low and high
      nitrogen deposition in China.
AB  - We added the stable isotope (15)N in the form of ((15)NH4)2SO4 and K(15)NO3 to
      forest ecosystems in eastern China under two different N deposition levels to
      study the fate of the different forms of deposited N. Prior to the addition of
      the (15)N tracers, the natural (15)N abundance ranging from -3.40/00 to +10.90/00
      in the forest under heavy N deposition at Dinghushan (DHS), and from -3.920/00 to
      +7.250/00 in the forest under light N deposition at Daxinganling (DXAL). Four
      months after the tracer application, the total (15)N recovery from the major
      ecosystem compartments ranged from 55.3% to 90.5%. The total (15)N recoveries
      were similar under the ((15)NH4)2SO4 tracer treatment in both two forest
      ecosystems, whereas the total (15)N recovery was significantly lower in the
      subtropical forest ecosystem at DHS than in the boreal forest ecosystem at DXAL
      under the K(15)NO3 tracer treatment. The (15)N assimilated into the tree biomass
      represented only 8.8% to 33.7% of the (15)N added to the forest ecosystems. In
      both of the tracer application treatments, more (15)N was recovered from the tree
      biomass in the subtropical forest ecosystem at DHS than the boreal forest
      ecosystem at DXAL. The amount of (15)N assimilated into tree biomass was greater
      under the K(15)NO3 tracer treatment than that of the ((15)NH4)2SO4 treatment in
      both forest ecosystems. This study suggests that, although less N was immobilized
      in the forest ecosystems under more intensive N deposition conditions, forest
      ecosystems in China strongly retain N deposition, even in areas under heavy N
      deposition intensity or in ecosystems undergoing spring freezing and thawing
      melts. Compared to ammonium deposition, deposited nitrate is released from the
      forest ecosystem more easily. However, nitrate deposition could be retained
      mostly in the plant N pool, which might lead to more C sequestration in these
      ecosystems.

PMID- 24586689
TI  - Automated detection of off-label drug use.
AB  - Off-label drug use, defined as use of a drug in a manner that deviates from its
      approved use defined by the drug's FDA label, is problematic because such uses
      have not been evaluated for safety and efficacy. Studies estimate that 21% of
      prescriptions are off-label, and only 27% of those have evidence of safety and
      efficacy. We describe a data-mining approach for systematically identifying off
      label usages using features derived from free text clinical notes and features
      extracted from two databases on known usage (Medi-Span and DrugBank). We trained
      a highly accurate predictive model that detects novel off-label uses among 1,602
      unique drugs and 1,472 unique indications. We validated 403 predicted uses across
      independent data sources. Finally, we prioritize well-supported novel usages for
      further investigation on the basis of drug safety and cost. 

PMID- 24586690
TI  - Runx1t1 (Runt-related transcription factor 1; translocated to, 1) epigenetically
      regulates the proliferation and nitric oxide production of microglia.
AB  - BACKGROUND: Microglia, the resident immune cells of the brain, undergo rapid
      proliferation and produce several proinflammatory molecules and nitric oxide (NO)
      when activated in neuropathological conditions. Runx1t1 (Runt-related
      transcription factor 1, translocated to 1) has been implicated in recruiting
      histone deacetylases (HDACs) for transcriptional repression, thereby regulating
      cell proliferation. In the present study, Runx1t1 expression was shown to
      localize in amoeboid microglial cells of the postnatal rat brain, being hardly
      detectable in ramified microglia of the adult brain. Moreover, a marked
      expression of Runx1t1was induced and translocated to nuclei in activated
      microglia in vitro and in vivo. In view of these findings, it was hypothesized
      that Runx1t1 regulates microglial functions during development and in
      neuropathological conditions. METHODS AND FINDINGS: siRNA-mediated knockdown of
      Runx1t1 significantly decreased the expression level of cell cycle-related gene,
      cyclin-dependent kinase 4 (Cdk4) and proliferation index in activated BV2
      microglia. It was also shown that HDAC inhibitor (HDACi) treatment mimics the
      effects of Runx1t1 knockdown on microglial proliferation, confirming that
      microglial proliferation is associated with Runx1t1 expression and HDACs
      activity. Further, Runx1t1 and HDACs were shown to promote neurotoxic effect of
      microglia by repressing expression of LAT2, L-aminoacid transporter-2 (cationic
      amino acid transporter, y+ system), which normally inhibits NO production. This
      was confirmed by chromatin immunoprecipitation (ChIP) assay, which revealed that
      Runx1t1 binds to the promoter region of LAT2 and this binding increased upon
      microglial activation. However, the enhanced binding of Runx1t1 to the LAT2
      promoter could not repress the LAT2 expression when the BV2 microglia cells were
      treated with HDACi, indicating that Runx1t1 requires HDACs to transcriptionally
      repress the expression of LAT2. CONCLUSION/INTERPRETATION: In conclusion, it is
      suggested that Runx1t1 controls proliferation and the neurotoxic effect of
      microglia by epigenetically regulating Cdk4 and LAT2 via its interaction with
      HDACs.

PMID- 24586691
TI  - Differential expression of alpha-synuclein in hippocampal neurons.
AB  - alpha-Synuclein is the major pathological component of synucleinopathies
      including Parkinson's disease and dementia with Lewy bodies. Recent studies have
      demonstrated that alpha-synuclein also plays important roles in the release of
      synaptic vesicles and synaptic membrane recycling in healthy neurons. However,
      the precise relationship between the pathogenicity and physiological functions of
      alpha-synuclein remains to be elucidated. To address this issue, we investigated
      the subcellular localization of alpha-synuclein in normal and pathological
      conditions using primary mouse hippocampal neuronal cultures. While some neurons
      expressed high levels of alpha-synuclein in presynaptic boutons and cell bodies,
      other neurons either did not or only very weakly expressed the protein. These
      alpha-synuclein-negative cells were identified as inhibitory neurons by
      immunostaining with specific antibodies against glutamic acid decarboxylase
      (GAD), parvalbumin, and somatostatin. In contrast, alpha-synuclein-positive
      synapses were colocalized with the excitatory synapse marker vesicular glutamate
      transporter-1. This expression profile of alpha-synuclein was conserved in the
      hippocampus in vivo. In addition, we found that while presynaptic alpha-synuclein
      colocalizes with synapsin, a marker of presynaptic vesicles, it is not essential
      for activity-dependent membrane recycling induced by high potassium treatment.
      Exogenous supply of preformed fibrils generated by recombinant alpha-synuclein
      was shown to promote the formation of Lewy body (LB) -like intracellular
      aggregates involving endogenous alpha-synuclein. GAD-positive neurons did not
      form LB-like aggregates following treatment with preformed fibrils, however,
      exogenous expression of human alpha-synuclein allowed intracellular aggregate
      formation in these cells. These results suggest the presence of a different
      mechanism for regulation of the expression of alpha-synuclein between excitatory
      and inhibitory neurons. Furthermore, alpha-synuclein expression levels may
      determine the efficiency of intracellular aggregate formation in different
      neuronal subtypes. 

PMID- 24586692
TI  - Improved detection of paroxysmal atrial fibrillation utilizing a software
      assisted electrocardiogram approach.
AB  - BACKGROUND: Automated complexity-based statistical stroke risk analysis (SRA) of
      electrocardiogram (ECG) recordings can be used to estimate the risk of paroxysmal
      atrial fibrillation (pAF). We investigated whether this method could improve the
      reliability of detection of patients at risk for pAF. METHODS AND RESULTS: Data
      from 12-lead ECGs, 24-h Holter ECGs, and SRA based on separate 1-hour Holter ECG
      snips were collected from three groups: 70 patients with a history of pAF but who
      showed no AF episode in the 12-lead ECG at study entry; 19 patients with chronic
      AF (at study entry); and 100 young healthy individuals. AF episodes were detected
      by Holter ECG in 19 of the 70 non-chronic AF patients (27.1% overall, 18.6% in
      the first hour), and 37 of these 70 patients were classified as at risk for pAF
      by SRA (representing a sensitivity of 52.9% based on the first hour of analyzed
      recording). Fifty-four of the 70 patients also showed a sinus rhythm in the first
      hour. SRA detected pAF risk in 23 of these 54 patients (representing a
      sensitivity of 42.6%). The Holter data showed at least 1 AF episode and at least
      1 hour of sinus rhythm in nine of the patients with pAF. For these patients, SRA
      classified 77.8% as being at risk in the first hour after the end of the AF
      episode, and 71.4% and 42.9% as being at risk in the second and third hours,
      respectively. SRA detected almost all cardiologist-confirmed AF episodes that had
      been recorded in 1-hour ECG snips (sensitivity, 99.2%; specificity, 99.2%).
      CONCLUSIONS: This outpatient study confirms previous findings that routine use of
      SRA could improve AF detection rates and thus may shorten the time between AF
      onset and initiation of prevention measures for patients at high risk for stroke.

PMID- 24586693
TI  - Evidence of a critical role for cellodextrin transporte 2 (CDT-2) in both
      cellulose and hemicellulose degradation and utilization in Neurospora crassa.
AB  - CDT-1 and CDT-2 are two cellodextrin transporters discovered in the filamentous
      fungus Neurospora crassa. Previous studies focused on characterizing the role of
      these transporters in only a few conditions, including cellulose degradation, and
      the function of these two transporters is not yet completely understood. In this
      study, we show that deletion of cdt-2, but not cdt-1, results in growth defects
      not only on Avicel but also on xylan. cdt-2 can be highly induced by xylan, and
      this mutant has a xylodextrin consumption defect. Transcriptomic analysis of the
      cdt-2 deletion strain on Avicel and xylan showed that major cellulase and
      hemicellulase genes were significantly down-regulated in the cdt-2 deletion
      strain and artificial over expression of cdt-2 in N. crassa increased cellulase
      and hemicellulase production. Together, these data clearly show that CDT-2 plays
      a critical role in hemicellulose sensing and utilization. This is the first time
      a sugar transporter has been assigned a function in the hemicellulose degradation
      pathway. Furthermore, we found that the transcription factor XLR-1 is the major
      regulator of cdt-2, while cdt-1 is primarily regulated by CLR-1. These results
      deepen our understanding of the functions of both cellodextrin transporters,
      particularly for CDT-2. Our study also provides novel insight into the mechanisms
      for hemicellulose sensing and utilization in N. crassa, and may be applicable to
      other cellulolytic filamentous fungi. 

PMID- 24586694
TI  - Storage duration of red blood cell transfusion and Clostridium difficile
      infection: a within person comparison.
AB  - OBJECTIVE: Randomized controlled trials demonstrated that red blood cell (RBC)
      transfusion elevates the risk of infection, and trials are underway to evaluate
      whether RBC storage affects outcomes. We previously reported that transfusion
      predicts Clostridium difficile infection (CDI) and, therefore, planned an
      investigation to examine this further using a more robust design. DESIGN: Within
      person case-crossover study. Hospitalizations in which CDI developed (n = 406)
      were compared to hospitalizations for the same individuals in which CDI did not
      occur (n = 949). Transfusion volume and storage duration were assessed prior to
      the onset of CDI. SETTING: University of Michigan Health System. PATIENTS:
      Participants were individuals with a diagnosis of CDI from July 2009 through June
      2012. MEASUREMENTS AND MAIN RESULTS: During the hospitalizations when CDI
      occurred, 34.7% of the patients received allogeneic RBC transfusions (mean
      volume, 688 ml) compared to 19.0% of patients in hospitalizations without CDI
      (mean volume, 180 ml). The odds of healthcare-associated CDI increased by 76%
      (95% CI 1.39-2.23) for every liter of RBCs transfused and was elevated in both
      nonsurgical (OR = 1.90) and surgical (OR = 1.86) hospitalizations. In patients
      who received RBC transfusions, the odds of developing CDI increased by 6% for
      every additional day of RBC stored and by 53% for every week of additional
      storage (P = 0.002). CONCLUSIONS: Hospitalizations in which a patient received a
      greater volume of RBC transfusions were more likely to be associated with the
      development of CDI. RBC units stored for a longer duration were associated with
      the development of healthcare-associated CDI after adjustment for RBC volume.

PMID- 24586695
TI  - Decreased seizure threshold in an eclampsia-like model induced in pregnant rats
      with lipopolysaccharide and pentylenetetrazol treatments.
AB  - OBJECTIVE: Eclampsia is a poorly understood but potentially fatal complication of
      pregnancy. Research to date on this disorder has been hampered by the lack of a
      suitable animal model. To correct this deficiency, this report describes the
      generation of a rat eclampsia-like model using pentylenetetrazol (PTZ) in a
      previously established rat preeclampsia model. METHOD: Rats were administered
      lipopolysaccharide (1.0 ug/kg) by tail vein injection on gestational day 14 to
      establish preeclampsia (PE). PE and control rats (non-pregnant, NP; normal
      pregnant, P) were injected intraperitoneally (i.p.) with PTZ (40 mg/kg) to induce
      seizures. In separate experiments, MgSO4 (270 mg/kg IP) was injected in advance
      of PTZ into PE rats to observe its effect on PTZ-induced seizures. RESULTS: PE
      conditions were verified in rats after LPS administration by significantly higher
      blood pressure (P<0.01) and urinary albumin excretion (P<0.05), elevated sFlt-1
      (P<0.05) and decreased PlGF serum levels (P<0.05), and evidence of hepatic
      dysfunction compared to control groups. PTZ successfully induced seizure activity
      in all groups studied. Latency to seizure was significantly (P<0.01) less in the
      PE-PTZ group (73.2 +/- 6.6 sec.) than in PTZ-treated controls (107.0 +/- 7.4
      sec.). Pretreatment with MgSO4 prolonged (P<0.05) latency to seizure, shortened
      seizure duration and decreased seizure rates. Significant increased (P<0.05) in
      the serum levels of the inflammatory cytokines TNF-alpha and IL-1beta in PE and
      PE-PTZ groups, and decreased (P<0.05) in their levels following MgSO4
      administration. CONCLUSION: This PTZ-induced eclampsia-like rat model is
      comparable to the human condition of eclampsia and may serve as a useful research
      tool for future studies of this disease. The increased inflammatory cytokines in
      preeclampsia are coincident with a decreased threshold for PTZ-induced seizures,
      suggesting that an inflammatory mechanism may contribute to the susceptibility to
      seizure activity and inflammation might have an important role in eclampsia.

PMID- 24586696
TI  - A panel of diverse assays to interrogate the interaction between glucokinase and
      glucokinase regulatory protein, two vital proteins in human disease.
AB  - Recent genetic and clinical evidence has implicated glucokinase regulatory
      protein (GKRP) in the pathogenesis of type 2 diabetes and related traits. The
      primary role of GKRP is to bind and inhibit hepatic glucokinase (GCK), a
      critically important protein in human health and disease that exerts a
      significant degree of control over glucose metabolism. As activation of GCK has
      been associated with improved glucose tolerance, perturbation of the GCK-GKRP
      interaction represents a potential therapeutic target for pharmacological
      modulation. Recent structural and kinetic advances are beginning to provide
      insight into the interaction of these two proteins. However, tools to
      comprehensively assess the GCK-GKRP interaction, particularly in the context of
      small molecules, would be a valuable resource. We therefore developed three
      robust and miniaturized assays for assessing the interaction between recombinant
      human GCK and GKRP: an HTRF assay, a diaphorase-coupled assay, and a luciferase
      coupled assay. The assays are complementary, featuring distinct mechanisms of
      detection (luminescence, fluorescence, FRET). Two assays rely on GCK enzyme
      activity modulation by GKRP while the FRET-based assay measures the GCK-GKRP
      protein-protein interaction independent of GCK enzymatic substrates and activity.
      All three assays are scalable to low volumes in 1536-well plate format, with
      robust Z' factors (>0.7). Finally, as GKRP sequesters GCK in the hepatocyte
      nucleus at low glucose concentrations, we explored cellular models of GCK
      localization and translocation. Previous findings from freshly isolated rat
      hepatocytes were confirmed in cryopreserved rat hepatocytes, and we further
      extended this study to cryopreserved human hepatocytes. Consistent with previous
      reports, there were several key differences between the rat and human systems,
      with our results suggesting that human hepatocytes can be used to interrogate GCK
      translocation in response to small molecules. The assay panel developed here
      should help direct future investigation of the GCK-GKRP interaction in these or
      other physiologically relevant human systems. 

PMID- 24586697
TI  - Two non-target recessive genes confer resistance to the anti-oomycete microtubule
      inhibitor zoxamide in Phytophthora capsici.
AB  - This study characterized isolates of P. capsici that had developed a novel
      mechanism of resistance to zoxamide, which altered the minimum inhibition
      concentration (MIC) but not the EC50. Molecular analysis revealed that the beta
      tubulin gene of the resistant isolates contained no mutations and was expressed
      at the same level as in zoxamide-sensitive isolates. This suggested that P.
      capsici had developed a novel non-target-site-based resistance to zoxamide.
      Analysis of the segregation ratio of zoxamide-resistance in the sexual progeny of
      the sensitive isolates PCAS1 and PCAS2 indicated that the resistance to zoxamide
      was controlled by one or more recessive nuclear genes. Furthermore, the
      segregation of resistance in the F1, F2, and BC1 progeny was in accordance with
      the theoretical ratios of the chi(2) test (P>0.05), which suggested that the
      resistance to zoxamide was controlled by two recessive genes, and that resistance
      to zoxamide occurred when at least one pair of these alleles was homozygous. This
      implies that the risk of zoxamide-resistance in P. capsici is low to moderate.
      Nevertheless this potential for resistance should be monitored closely,
      especially if two compatible mating types co-exist in the same field. 

PMID- 24586698
TI  - A novel predictive equation for potential diagnosis of cholangiocarcinoma.
AB  - Cholangiocarcinoma (CCA) is the second most common-primary liver cancer. The
      difficulties in diagnosis limit successful treatment of CCA. At present,
      histological investigation is the standard diagnosis for CCA. However, there are
      some poor-defined tumor tissues which cannot be definitively diagnosed by general
      histopathology. As molecular signatures can define molecular phenotypes related
      to diagnosis, prognosis, or treatment outcome, and CCA is the second most common
      cancer found after hepatocellularcarcinoma (HCC), the aim of this study was to
      develop a predictive model which differentiates CCA from HCC and normal liver
      tissues. An in-house PCR array containing 176 putative CCA marker genes was
      tested with the training set tissues of 20 CCA and 10 HCC cases. The molecular
      signature of CCA revealed the prominent expression of genes involved in cell
      adhesion and cell movement, whereas HCC showed elevated expression of genes
      related to cell proliferation/differentiation and metabolisms. A total of 69
      genes differentially expressed in CCA and HCC were optimized statistically to
      formulate a diagnostic equation which distinguished CCA cases from HCC cases.
      Finally, a four-gene diagnostic equation (CLDN4, HOXB7, TMSB4 and TTR) was
      formulated and then successfully validated using real-time PCR in an independent
      testing set of 68 CCA samples and 77 non-CCA controls. Discrimination analysis
      showed that a combination of these genes could be used as a diagnostic marker for
      CCA with better diagnostic parameters with high sensitivity and specificity than
      using a single gene marker or the usual serum markers (CA19-9 and CEA). This new
      combination marker may help physicians to identify CCA in liver tissues when the
      histopathology is uncertain. 

PMID- 24586699
TI  - Suppressive effects of irbesartan on inflammation and apoptosis in
      atherosclerotic plaques of apoE-/- mice: molecular imaging with 14C-FDG and 99mTc
      annexin A5.
AB  - OBJECTIVES: To investigate the effects of irbesartan on inflammation and
      apoptosis in atherosclerotic plaques by histochemical examination and molecular
      imaging using (14)C-FDG and (99m)Tc-annexin A5. BACKGROUND: Irbesartan has a
      peroxisome proliferator-activated receptor gamma (PPARgamma) activation property
      in addition to its ability to block the AT1 receptor. Accordingly, irbesartan may
      exert further anti-inflammatory and anti-apoptotic effects in atherosclerotic
      plaques. However, such effects of irbesartan have not been fully investigated.
      Molecular imaging using (18)F-FDG and (99m)Tc-annexin A5 is useful for evaluating
      inflammation and apoptosis in atherosclerotic plaques. METHODS: Female apoE(-/-)
      mice were treated with irbesartan-mixed (50 mg/kg/day) or irbesartan-free
      (control) diet for 12 weeks (n = 11/group). One week after the treatment, the
      mice were co-injected with (14)C-FDG and (99m)Tc-annexin A5, and cryostat
      sections of the aortic root were prepared. Histochemical examination with Movat's
      pentachrome (plaque size), Oil Red O (lipid deposition), Mac-2 (macrophage
      infiltration), and TUNEL (apoptosis) stainings were performed. Dual-tracer
      autoradiography was carried out to evaluate the levels of (14)C-FDG and (99m)Tc
      annexin A5 in plaques (%ID*kg). In vitro experiments were performed to
      investigate the mechanism underlying the effects. RESULTS: Histological
      examination indicated that irbesartan treatment significantly reduced plaque size
      (to 56.4%+/-11.1% of control), intra-plaque lipid deposition (53.6%+/-20.2%) and
      macrophage infiltration (61.9%+/-20.8%) levels, and the number of apoptotic cells
      (14.5%+/-16.6%). (14)C-FDG (43.0%+/-18.6%) and (99m)Tc-annexin A5 levels (45.9%+/
      16.8%) were also significantly reduced by irbesartan treatment. Irbesartan
      significantly suppressed MCP-1 mRNA expression in TNF-alpha stimulated THP-1
      monocytes (64.8%+/-8.4% of un-treated cells). PPARgamma activation was observed
      in cells treated with irbesartan (134%+/-36% at 3 uM to 3329%+/-218% at 81 uM) by
      a PPARgamma reporter assay system. CONCLUSIONS: Remissions of inflammation and
      apoptosis as potential therapeutic effects of irbesartan on atherosclerosis were
      observed. The usefulness of molecular imaging using (18)F-FDG and (99m)Tc-annexin
      A5 for evaluating the therapeutic effects of irbesartan on atherosclerosis was
      also suggested.

PMID- 24586700
TI  - NOD2 polymorphisms associated with cancer risk: a meta-analysis.
AB  - BACKGROUND: Emerging evidence indicated that common polymorphisms of NOD2 might
      impact individual susceptibility to cancer. However, the results from published
      studies were inconclusive. The aim of this meta-analysis was to elucidate whether
      NOD2 polymorphisms were associated with cancer risk. METHODS: A systematically
      literature search was performed by using electronic databases including PubMed
      and Web of Science. ORs and their 95% CI were used to assess the strength of
      association between NOD2 gene polymorphisms and cancer risks. RESULTS: Thirty
      case-control studies were included in this meta-analysis. The pooled analysis
      indicated that NOD2 rs2066842 C/T polymorphism was not significantly associated
      with cancer risk; for NOD2 rs2066844 C/T polymorphism, (TT+CT) genotype was
      associated with increased cancer risk compared with wild-type CC genotype (OR =
      1.32, 95% CI = 1.01-1.72, P = 0.041); for NOD2 rs2066845 C/G polymorphism,
      individuals with (CC+CG) genotype were significantly associated with increased
      cancer risk compared with GG genotype (OR = 1.32, 95% CI = 1.01-1.72, P = 0.040);
      for NOD2 rs2066847 (3020insC) polymorphism, carriers of (insC/insC+insC/-)
      genotype were significantly associated with increased cancer risk compared with 
      /- carriers (OR = 1.23, 95% CI = 1.10-1.38, P<0.001). In the subgroup analysis of
      cancer type, (insC/insC+insC/-) genotype was significantly associated with
      increased risk of colorectal cancer, gastric cancer and MALT lymphoma, breast
      cancer, lung cancer, laryngeal cancer but not with urogenital cancer, pancreatic
      cancer, melanoma or non-Hodgkin lymphoma. CONCLUSION: NOD2 rs2066844 C/T,
      rs2066845 C/G and rs2066847 (3020insC) polymorphisms might be associated with
      increased cancer risk. No significant association was observed between NOD2
      rs2066842 C/T polymorphism and cancer risk. Further large-scale and well-designed
      studies are still needed to confirm the results of our meta-analysis.

PMID- 24586701
TI  - Plasma sCD14 as a biomarker to predict pulmonary exacerbations in cystic
      fibrosis.
AB  - BACKGROUND: One in four cystic fibrosis (CF) patients diagnosed with a pulmonary
      exacerbation will not recover their baseline lung function despite standard
      treatment. This highlights the importance of preventing such events. Clinical
      decision-making can be improved through a simple blood test that predicts
      individuals at elevated short-term risk of an exacerbation. METHODS: We obtained
      plasma samples from 30 stable CF patients from the St. Paul's Hospital Adult CF
      Clinic (Vancouver, Canada). For 15 patients, an additional plasma sample was
      obtained during an exacerbation. Soluble CD14 (sCD14) and C-reactive protein
      (CRP) were quantified using ELISA kits. Myeloperoxidase (MPO), interleukin(IL)-6,
      IL-1beta, monocyte chemoattractant protein-1 (MCP-1), vascular endothelial growth
      factor (VEGF), and granulocyte colony-stimulating factor (G-CSF) were quantified
      using LuminexTM immunoassays. Stable state biomarker levels were examined in
      their ability to predict individuals that would experience a pulmonary
      exacerbation requiring intravenous (IV) antibiotics within 4 months. Paired
      stable and exacerbation plasma biomarker levels were also compared. RESULTS:
      sCD14 levels were significantly higher in patients that experienced a pulmonary
      exacerbation requiring IV antibiotics within 4 months (p = 0.001). sCD14 cut-off
      value of 1450 ng/mL was associated with an area under the curve of 0.91 (95% CI
      0.83-0.99) for predicting an exacerbation within 4 months of a stable visit, with
      a sensitivity of 100% and specificity of 82%. Plasma sCD14 levels were
      significantly higher during exacerbations than during periods of clinical
      stability (p = 0.03). CONCLUSIONS: Plasma sCD14 is a promising biomarker for
      identifying CF patients who will exacerbate within 4 months of a stable visit but
      requires further study in larger, independent cohorts.

PMID- 24586702
TI  - Repair of microdamage in osteonal cortical bone adjacent to bone screw.
AB  - Up to date, little is known about the repair mode of microdamage in osteonal
      cortical bone resulting from bone screw implantation. In this study, self-tapping
      titanium cortical bone screws were inserted into the tibial diaphyses of 24 adult
      male rabbits. The animals were sacrificed at 1 day, 2 weeks, 1 month and 2 months
      after surgery. Histomorphometric measurement and confocal microscopy were
      performed on basic fuchsin stained bone sections to examine the morphological
      characteristics of microdamage, bone resorption activity and spatial relationship
      between microdamage and bone resorption. Diffuse and linear cracks were coexisted
      in peri-screw bone. Intracortical bone resorption was significantly increased 2
      weeks after screw installation and reach to the maximum at 1 month. There was no
      significant difference in bone resorption between 1-month and 2-months groups.
      Microdamage was significantly decreased within 1 month after surgery. Bone
      resorption was predisposed to occur in the region of <100 um from the bone-screw
      interface, where had extensive diffuse damage mixed with linear cracks. Different
      patterns of resorption cavities appeared in peri-screw bone. These data suggest
      that 1) the complex microdamage composed of diffuse damage and linear cracks is a
      strong stimulator for initiating targeted bone remodeling; 2) bone resorption
      activities taking place on the surfaces of differently oriented Haversian and
      Volkmann canals work in a team for the repair of extensive microdamage; 3)
      targeted bone remodeling is a short-term reaction to microdamage and thereby it
      may not be able to remove all microdamage resulting from bone screw insertion. 

PMID- 24586703
TI  - The characteristics of chronic inflammatory demyelinating polyneuropathy in
      patients with and without diabetes--an observational study.
AB  - INTRODUCTION: We aimed to determine whether the clinical characteristics and
      electrodiagnostic classification of nerve injury, and response to treatment
      differed in patients diagnosed with chronic inflammatory demyelinating
      polyneuropathy (CIDP) with and without diabetes. METHODS: CIDP patients with
      diabetes (CIDP+DM) (n = 67) and without diabetes (CIDP-DM) (n = 67) underwent
      clinical examination and nerve conduction studies (NCS). CIDP-DM patients were
      selected using age and gender matching with the existing CIDP+DM cohort. Patients
      treated with immunotherapies were classified as responders (R) (n = 46) or non
      responders (NR) (n = 54) based on clinical response to treatment. The groups were
      compared using analysis of variance, contingency tables and Kruskal-Wallis
      analyses. RESULTS: CIDP+DM subjects had more severe neuropathy based on higher
      lower limb vibration potential thresholds (VPT)(p = 0.004), higher Toronto
      Clinical Neuropathy Score (TCNS) (p = 0.0009), more proximal weakness (p = 0.03),
      more gait abnormality (p = 0.03) and more abnormal NCS. CIDP+DM subjects had more
      abnormal sural NCS with lower sural sensory nerve action potential amplitudes
      (2.4+/-3.0 uV, 6.6+/-6.0 uV, p<0.0001) and slower sural nerve conduction
      velocities (38.6+/-5.4 m/s, 41.0+/-5.3 m/s, p = 0.04). CIDP-DM subjects were more
      likely to receive immune therapies (93% vs 57%, p = <0.0001), despite no
      significant differences in treatment responder rates (p = 0.71). Patients who
      responded to therapy had shorter duration of CIDP than non-responders (8.0+/-6.0
      y vs 11.9+/-7.6 y, p = 0.004). DISCUSSION: The clinical phenotype and
      electrophysiological profile of CIDP patients differs according to the presence
      or absence of diabetes. Despite CIDP+DM patients having more severe clinical and
      electrophysiological neuropathy, they are less likely to receive disease
      modifying/specific therapy, yet have similar response rates to treatment as those
      without diabetes. Specifically, the duration of neuropathy - not diabetes status 
      was associated with treatment response.

PMID- 24586705
TI  - Contagious deposition of seeds in spider monkeys' sleeping trees limits effective
      seed dispersal in fragmented landscapes.
AB  - The repeated use of sleeping sites by frugivorous vertebrates promotes the
      deposition and aggregation of copious amounts of seeds in these sites. This
      spatially contagious pattern of seed deposition has key implications for seed
      dispersal, particularly because such patterns can persist through recruitment.
      Assessing the seed rain patterns in sleeping sites thus represents a fundamental
      step in understanding the spatial structure and regeneration of plant
      assemblages. We evaluated the seed rain produced by spider monkeys (Ateles
      geoffroyi) in latrines located beneath 60 sleeping trees in two continuous forest
      sites (CFS) and three forest fragments (FF) in the Lacandona rainforest, Mexico.
      We tested for differences among latrines, among sites, and between forest
      conditions in the abundance, diversity (alpha-, beta- and, gamma-components) and
      evenness of seed assemblages. We recorded 45,919 seeds >= 5 mm (in length) from
      68 species. The abundance of seeds was 1.7 times higher in FF than in CFS,
      particularly because of the dominance of a few plant species. As a consequence,
      community evenness tended to be lower within FF. beta-diversity of common and
      dominant species was two times greater among FF than between CFS. Although mean
      alpha-diversity per latrine did not differ among sites, the greater beta
      diversity among latrines in CFS increased gamma-diversity in these sites,
      particularly when considering common and dominant species. Our results support
      the hypothesis that fruit scarcity in FF can 'force' spider monkeys to deplete
      the available fruit patches more intensively than in CFS. This feeding strategy
      can limit the effectiveness of spider monkeys as seed dispersers in FF, because
      (i) it can limit the number of seed dispersers visiting such fruit patches; (ii)
      it increases seed dispersal limitation; and (iii) it can contribute to the
      floristic homogenization (i.e., reduced beta-diversity among latrines) in
      fragmented landscapes.

PMID- 24586704
TI  - Optimization of a one-step heat-inducible in vivo mini DNA vector production
      system.
AB  - While safer than their viral counterparts, conventional circular covalently
      closed (CCC) plasmid DNA vectors offer a limited safety profile. They often
      result in the transfer of unwanted prokaryotic sequences, antibiotic resistance
      genes, and bacterial origins of replication that may lead to unwanted
      immunostimulatory responses. Furthermore, such vectors may impart the potential
      for chromosomal integration, thus potentiating oncogenesis. Linear covalently
      closed (LCC), bacterial sequence free DNA vectors have shown promising clinical
      improvements in vitro and in vivo. However, the generation of such minivectors
      has been limited by in vitro enzymatic reactions hindering their downstream
      application in clinical trials. We previously characterized an in vivo
      temperature-inducible expression system, governed by the phage lambda pL promoter
      and regulated by the thermolabile lambda CI[Ts]857 repressor to produce
      recombinant protelomerase enzymes in E. coli. In this expression system,
      induction of recombinant protelomerase was achieved by increasing culture
      temperature above the 37 degrees C threshold temperature. Overexpression of
      protelomerase led to enzymatic reactions, acting on genetically engineered multi
      target sites called "Super Sequences" that serve to convert conventional CCC
      plasmid DNA into LCC DNA minivectors. Temperature up-shift, however, can result
      in intracellular stress responses and may alter plasmid replication rates; both
      of which may be detrimental to LCC minivector production. We sought to optimize
      our one-step in vivo DNA minivector production system under various induction
      schedules in combination with genetic modifications influencing plasmid
      replication, processing rates, and cellular heat stress responses. We assessed
      different culture growth techniques, growth media compositions, heat induction
      scheduling and temperature, induction duration, post-induction temperature, and
      E. coli genetic background to improve the productivity and scalability of our
      system, achieving an overall LCC DNA minivector production efficiency of ~ 90%.We
      optimized a robust technology conferring rapid, scalable, one-step in vivo
      production of LCC DNA minivectors with potential application to gene transfer
      mediated therapeutics.

PMID- 24586706
TI  - Arachidonic acid enhances turnover of the dermal skeleton: studies on zebrafish
      scales.
AB  - In fish nutrition, the ratio between omega-3 and omega-6 poly-unsaturated fatty
      acids influences skeletal development. Supplementation of fish oils with
      vegetable oils increases the content of omega-6 fatty acids, such as arachidonic
      acid in the diet. Arachidonic acid is metabolized by cyclooxygenases to
      prostaglandin E2, an eicosanoid with effects on bone formation and remodeling. To
      elucidate effects of poly-unsaturated fatty acids on developing and existing
      skeletal tissues, zebrafish (Danio rerio) were fed (micro-) diets low and high in
      arachidonic acid content. Elasmoid scales, dermal skeletal plates, are ideal to
      study skeletal metabolism in zebrafish and were exploited in the present study.
      The fatty acid profile resulting from a high arachidonic acid diet induced mild
      but significant increase in matrix resorption in ontogenetic scales of adult
      zebrafish. Arachidonic acid affected scale regeneration (following removal of
      ontogenetic scales): mineral deposition was altered and both gene expression and
      enzymatic matrix metalloproteinase activity changed towards enhanced osteoclastic
      activity. Arachidonic acid also clearly stimulates matrix metalloproteinase
      activity in vitro, which implies that resorptive effects of arachidonic acid are
      mediated by matrix metalloproteinases. The gene expression profile further
      suggests that arachidonic acid increases maturation rate of the regenerating
      scale; in other words, enhances turnover. The zebrafish scale is an excellent
      model to study how and which fatty acids affect skeletal formation. 

PMID- 24586707
TI  - Determination of acceptor concentration, depletion width, donor level movement
      and sensitivity factor of ZnO on diamond heterojunction under UV illumination.
AB  - The concentration of acceptor carriers, depletion width, magnitude of donor level
      movement as well as the sensitivity factor are determined from the UV response of
      a heterojunction consisting of ZnO on type IIb diamond. From the comparison of
      the I-V measurements in dark condition and under UV illumination we show that the
      acceptor concentration (~10(17) cm(-3)) can be estimated from p-n junction
      properties. The depletion width of the heterojunction is calculated and is shown
      to extend farther into the ZnO region in dark condition. Under UV illumination,
      the depletion width shrinks but penetrates both materials equally. The
      ultraviolet illumination causes the donor level to move closer to the conduction
      band by about 50 meV suggesting that band bending is reduced to allow more
      electrons to flow from the intrinsically n-type ZnO. The sensitivity factor of
      the device calculated from the change of threshold voltages, the ratio of dark
      and photocurrents and identity factor is consistent with experimental data. 

PMID- 24586708
TI  - High-throughput screening identifies idarubicin as a preferential inhibitor of
      smooth muscle versus endothelial cell proliferation.
AB  - Intimal hyperplasia is the cause of the recurrent occlusive vascular disease
      (restenosis). Drugs currently used to treat restenosis effectively inhibit smooth
      muscle cell (SMC) proliferation, but also inhibit the growth of the protective
      luminal endothelial cell (EC) lining, leading to thrombosis. To identify
      compounds that selectively inhibit SMC versus EC proliferation, we have developed
      a high-throughput screening (HTS) format using human cells and have employed this
      to screen a multiple compound collection (NIH Clinical Collection). We developed
      an automated, accurate proliferation assay in 96-well plates using human aortic
      SMCs and ECs. Using this HTS format we screened a 447-drug NIH Clinical Library.
      We identified 11 compounds that inhibited SMC proliferation greater than 50%,
      among which idarubicin exhibited a unique feature of preferentially inhibiting
      SMC versus EC proliferation. Concentration-response analysis revealed this
      differential effect most evident over an ~10 nM-5 uM window. In vivo testing of
      idarubicin in a rat carotid injury model at 14 days revealed an 80% reduction of
      intimal hyperplasia and a 45% increase of lumen size with no significant effect
      on re-endothelialization. Taken together, we have established a HTS assay of
      human vascular cell proliferation, and identified idarubicin as a selective
      inhibitor of SMC versus EC proliferation both in vitro and in vivo. Screening of
      larger and more diverse compound libraries may lead to the discovery of next
      generation therapeutics that can inhibit intima hyperplasia without impairing re
      endothelialization. 

PMID- 24586710
TI  - Using gastrocnemius sEMG and plasma alpha-synuclein for the prediction of
      freezing of gait in Parkinson's disease patients.
AB  - Freezing of gait (FOG) is a complicated gait disturbance in Parkinson's disease
      (PD) and a relevant subclinical predictor algorithm is lacking. The main purpose
      of this study is to explore the potential value of surface electromyograph (sEMG)
      and plasma alpha-synuclein levels as predictors of the FOG seen in PD. 21 PD
      patients and 15 normal controls were recruited. Motor function was evaluated
      using the Unified Parkinson's Disease Rating Scale (UPDRS) and Freezing of gait
      questionnaire (FOG-Q). Simultaneously, gait analysis was also performed using
      VICON capture system in PD patients and sEMG data was recorded as well. Total
      plasma alpha-synuclein was quantitatively assessed by Luminex assay in all
      participants. Recruited PD patients were classified into two groups: PD patients
      with FOG (PD+FOG) and without FOG (PD-FOG), based on clinical manifestation, the
      results of the FOG-Q and VICON capture system. PD+FOG patients displayed higher
      FOG-Q scores, decreased walking speed, smaller step length, smaller stride length
      and prolonged double support time compared to the PD-FOG in the gait trial. sEMG
      data indicated that gastrocnemius activity in PD+FOG patients was significantly
      reduced compared to PD-FOG patients. In addition, plasma alpha-synuclein levels
      were significantly decreased in the PD+FOG group compared to control group;
      however, no significant difference was found between the PD+FOG and PD-FOG
      groups. Our study revealed that gastrocnemius sEMG could be used to evaluate
      freezing gait in PD patients, while plasma alpha-synuclein might discriminate
      freezing of gait in PD patients from normal control, though no difference was
      found between the PD+FOG and PD-FOG groups. 

PMID- 24586709
TI  - PD-1 blockade and OX40 triggering synergistically protects against tumor growth
      in a murine model of ovarian cancer.
AB  - The co-inhibitory receptor Programmed Death-1 (PD-1) curtails immune responses
      and prevent autoimmunity, however, tumors exploit this pathway to escape from
      immune destruction. The co-stimulatory receptor OX40 is upregulated on T cells
      following activation and increases their clonal expansion, survival and cytokine
      production when engaged. Although antagonistic anti-PD-1 or agonistic anti-OX40
      antibodies can promote the rejection of several murine tumors, some poorly
      immunogenic tumors were refractory to this treatment. In the present study, we
      evaluated the antitumor effects and mechanisms of combinatorial PD-1 blockade and
      OX40 triggering in a murine ID8 ovarian cancer model. Although individual anti-PD
      1 or OX40 mAb treatment was ineffective in tumor protection against 10-day
      established ID8 tumor, combined anti-PD-1/OX40 mAb treatment markedly inhibited
      tumor outgrowth with 60% of mice tumor free 90 days after tumor inoculation.
      Tumor protection was associated with a systemic immune response with memory and
      antigen specificity and required CD4(+) cells and CD8(+) T cells. The anti-PD
      1/OX40 mAb treatment increased CD4(+) and CD8(+) cells and decreased
      immunosuppressive CD4(+)FoxP3(+) regulatory T (Treg) cells and CD11b(+)Gr-1(+)
      myeloid suppressor cells (MDSC), giving rise to significantly higher ratios of
      both effector CD4(+) and CD8(+) cells to Treg and MDSC in peritoneal cavity;
      Quantitative RT-PCR data further demonstrated the induction of a local
      immunostimulatory milieu by anti-PD-1/OX40 mAb treatment. The splenic CD8(+) T
      cells from combined mAb treated mice produced high levels of IFN-gamma upon tumor
      antigen stimulation and exhibited antigen-specific cytolytic activity. To our
      knowledge, this is the first study testing the antitumor effects of combined anti
      PD-1/OX40 mAb in a murine ovarian cancer model, and our results provide a
      rationale for clinical trials evaluating ovarian cancer immunotherapy using this
      combination of mAb. 

PMID- 24586711
TI  - Prevention of neural tube defects: a cross-sectional study of the uptake of folic
      acid supplementation in nearly half a million women.
AB  - BACKGROUND: Taking folic acid supplements before pregnancy to reduce the risk of
      a neural tube defect (NTD) is especially important in countries without universal
      folic acid fortification. The extent of folic acid supplementation among women
      who had antenatal screening for Down's syndrome and NTDs at the Wolfson Institute
      of Preventive Medicine, London between 1999 and 2012 was assessed. METHODS AND
      FINDINGS: 466,860 women screened provided details on folic acid supplementation.
      The proportion of women who took folic acid supplements before pregnancy was
      determined according to year and characteristics of the women. The proportion of
      women taking folic acid supplements before pregnancy declined from 35% (95% CI
      34%-35%) in 1999-2001 to 31% (30%-31%) in 2011-2012. 6% (5%-6%) of women aged
      under 20 took folic acid supplements before pregnancy compared with 40% of women
      aged between 35 and 39. Non-Caucasian women were less likely to take folic acid
      supplements before pregnancy than Caucasian women; Afro-Caribbean 17% (16%-17%),
      Oriental 25% (24%-25%) and South Asian 20% (20%-21%) compared with 35% (35%-35%)
      for Caucasian women. 51% (48%-55%) of women who previously had an NTD pregnancy
      took folic acid supplements before the current pregnancy. CONCLUSIONS: The policy
      of folic acid supplementation is failing and has led to health inequalities. This
      study demonstrates the need to fortify flour and other cereal grain with folic
      acid in all countries of the world.

PMID- 24586712
TI  - Iron chelation by deferoxamine prevents renal interstitial fibrosis in mice with
      unilateral ureteral obstruction.
AB  - Renal fibrosis plays an important role in the onset and progression of chronic
      kidney diseases (CKD). Although several mechanisms underlying renal fibrosis and
      candidate drugs for its treatment have been identified, the effect of iron
      chelator on renal fibrosis remains unclear. In the present study, we examined the
      effect of an iron chelator, deferoxamine (DFO), on renal fibrosis in mice with
      surgically induced unilateral ureter obstruction (UUO). Mice were divided into 4
      groups: UUO with vehicle, UUO with DFO, sham with vehicle, and sham with DFO. One
      week after surgery, augmented renal tubulointerstitial fibrosis and the
      expression of collagen I, III, and IV increased in mice with UUO; these changes
      were suppressed by DFO treatment. Similarly, UUO-induced macrophage infiltration
      of renal interstitial tubules was reduced in UUO mice treated with DFO. UUO
      induced expression of inflammatory cytokines and extracellular matrix proteins
      was abrogated by DFO treatment. DFO inhibited the activation of the transforming
      growth factor-beta1 (TGF-beta1)-Smad3 pathway in UUO mice. UUO-induced NADPH
      oxidase activity and p22(phox) expression were attenuated by DFO. In the kidneys
      of UUO mice, divalent metal transporter 1, ferroportin, and ferritin expression
      was higher and transferrin receptor expression was lower than in sham-operated
      mice. Increased renal iron content was observed in UUO mice, which was reduced by
      DFO treatment. These results suggest that iron reduction by DFO prevents renal
      tubulointerstitial fibrosis by regulating TGF-beta-Smad signaling, oxidative
      stress, and inflammatory responses. 

PMID- 24586713
TI  - Discovery of selective inhibitors of the Clostridium difficile dehydroquinate
      dehydratase.
AB  - A vibrant and healthy gut flora is essential for preventing the proliferation of
      Clostridium difficile, a pathogenic bacterium that causes severe gastrointestinal
      symptoms. In fact, most C. difficile infections (CDIs) occur after broad-spectrum
      antibiotic treatment, which, by eradicating the commensal gut bacteria, allows
      its spores to proliferate. Hence, a C. difficile specific antibiotic that spares
      the gut flora would be highly beneficial in treating CDI. Towards this goal, we
      set out to discover small molecule inhibitors of the C. difficile enzyme
      dehydroquinate dehydratase (DHQD). DHQD is the 3(rd) of seven enzymes that
      compose the shikimate pathway, a metabolic pathway absent in humans, and is
      present in bacteria as two phylogenetically and mechanistically distinct types.
      Using a high-throughput screen we identified three compounds that inhibited the
      type I C. difficile DHQD but not the type II DHQD from Bacteroides
      thetaiotaomicron, a highly represented commensal gut bacterial species. Kinetic
      analysis revealed that the compounds inhibit the C. difficile enzyme with Ki
      values ranging from 10 to 20 uM. Unexpectedly, kinetic and biophysical studies
      demonstrate that inhibitors also exhibit selectivity between type I DHQDs,
      inhibiting the C. difficile but not the highly homologous Salmonella enterica
      DHQD. Therefore, the three identified compounds seem to be promising lead
      compounds for the development of C. difficile specific antibiotics. 

PMID- 24586714
TI  - Measuring cytotoxicity by bioluminescence imaging outperforms the standard
      chromium-51 release assay.
AB  - The chromium-release assay developed in 1968 is still the most commonly used
      method to measure cytotoxicity by T cells and by natural killer cells. Target
      cells are loaded in vitro with radioactive chromium and lysis is determined by
      measuring chromium in the supernatant released by dying cells. Since then,
      alternative methods have been developed using different markers of target cell
      viability that do not involve radioactivity. Here, we compared and contrasted a
      bioluminescence (BLI)-based cytotoxicity assay to the standard radioactive
      chromium-release assay using an identical set of effector cells and tumor target
      cells. For this, we stably transduced several human and murine tumor cell lines
      to express luciferase. When co-cultured with cytotoxic effector cells, highly
      reproducible decreases in BLI were seen in an effector to target cell dose
      dependent manner. When compared to results obtained from the chromium release
      assay, the performance of the BLI-based assay was superior, because of its
      robustness, increased signal-to-noise ratio, and faster kinetics. The
      reduced/delayed detection of cytotoxicity by the chromium release method was
      attributable to the association of chromium with structural components of the
      cell, which are released quickly by detergent solubilization but not by hypotonic
      lysis. We conclude that the (BLI)-based measurement of cytotoxicity offers a
      superior non-radioactive alternative to the chromium-release assay that is more
      robust and quicker to perform. 

PMID- 24586715
TI  - School and community-based interventions for refugee and asylum seeking children:
      a systematic review.
AB  - BACKGROUND: Research for effective psychological interventions for refugee and
      asylum-seeking children has intensified. The need for interventions in
      environments more easily accessed by children and families is especially relevant
      for newly arrived populations. This paper reviews the literature on school and
      community-based interventions aimed at reducing psychological disorders in
      refugee and asylum-seeking children. METHODS AND FINDINGS: Comprehensive searches
      were conducted in seven databases and further information was obtained through
      searching reference lists, grey literature, and contacting experts in the field.
      Studies were included if they reported on the efficacy of a school or community
      based mental health intervention for refugee or asylum-seeking children. Two
      independent reviewers made the final study selection, extracted data, and reached
      consensus on study quality. Results were summarized descriptively. The marked
      heterogeneity of studies excluded conducting a meta-analysis but study effect
      sizes were calculated where possible. Twenty one studies met inclusion criteria
      for the review reporting on interventions for approximately 1800 refugee
      children. Fourteen studies were carried out in high-income countries in either a
      school (n = 11) or community (n = 3) setting and seven studies were carried out
      in refugee camps. Interventions were either primarily focused on the verbal
      processing of past experiences (n = 9), or on an array of creative art techniques
      (n = 7) and others used a combination of these interventions (n = 5). While both
      intervention types reported significant changes in symptomatology, effect sizes
      ranged from 0.31 to 0.93 and could mainly be calculated for interventions
      focusing on the verbal processing of past experiences. CONCLUSIONS: Only a small
      number of studies fulfilled inclusion criteria and the majority of these were in
      the school setting. The findings suggest that interventions delivered within the
      school setting can be successful in helping children overcome difficulties
      associated with forced migration.

PMID- 24586716
TI  - The impact of diabetes on the labour force participation and income poverty of
      workers aged 45-64 years in Australia.
AB  - OBJECTIVE: To quantify the poverty status and level of disadvantage experienced
      by Australians aged 45-64 years who have left the labour force due to diabetes in
      2010. RESEARCH DESIGN AND METHODS: A purpose-built microsimulation model,
      Health&WealthMOD2030, was used to estimate the poverty status and level of
      disadvantage of those aged 45-64 years who prematurely retire from the workforce
      due to diabetes. A multiple regression model was used to identify significant
      differences in rates of income poverty and the degree of disadvantage between
      those out of the labour force due to diabetes and those employed full- or part
      time with no diabetes. RESULTS: 63.9% of people aged 45-64 years who were out of
      the labour force due to diabetes were in poverty in 2010. The odds of being in
      poverty for those with no diabetes and employed full-time (OR of being in poverty
      0.02 95%CI: 0.01-0.04) or part-time (OR of being in poverty 0.10 95%CI: 0.05
      0.23) are significantly lower than those for persons not in the labour force due
      to diabetes. Amongst those with diabetes, those who were able to stay in either
      full- or part-time employment were as much as 97% less likely to be in poverty
      than those who had to retire early because of the condition. Sensitivity analysis
      was used to assess impacts of different poverty line thresholds and key
      socioeconomic predictors of poverty. CONCLUSIONS: This study has shown that
      having diabetes and not being in the labour force because of this condition
      significantly increases the chances of living in poverty. Intervening to prevent
      or delay the onset of diabetes is likely to improve their living standards.

PMID- 24586717
TI  - Difficulties in eliminating measles and controlling rubella and mumps: a cross
      sectional study of a first measles and rubella vaccination and a second measles,
      mumps, and rubella vaccination.
AB  - BACKGROUND: The reported coverage of the measles-rubella (MR) or measles-mumps
      rubella (MMR) vaccine is greater than 99.0% in Zhejiang province. However, the
      incidence of measles, mumps, and rubella remains high. In this study, we assessed
      MMR seropositivity and disease distribution by age on the basis of the current
      vaccination program, wherein the first dose of MR is administered at 8 months and
      the second dose of MMR is administered at 18-24 months. METHODS: Cross-sectional
      serological surveys of MMR antibodies were conducted by collecting
      epidemiological data in Zhejiang province, China in 2011. In total, 1015
      participants were randomly selected from two surveillance sites. Serum MMR
      specific immunoglobulin G levels were tested by enzyme-linked immunosorbent
      assay. The geometric mean titers and seroprevalence with 95% confidence intervals
      (CIs) were calculated by age and gender. Proportions of different dose of vaccine
      by age by vaccine were also identified. Statistically significant differences
      between categories were assessed by the Chi-square test. RESULTS: Over 95%
      seroprevalence rates of measles were seen in all age groups except <7 months
      infants. Children aged 5-9 years were shown lower seropositivity rates of mumps
      while elder adolescences and young adults were presented lower rubella
      seroprevalence. Especially, rubella seropositivity was significantly lower in
      female adults than in male. Nine measles cases were unvaccinated or unknown
      vaccination history. Among them, 66.67% (6/9) patients were aged 20-29 years
      while 33.33% (3/9) were infants aged 8-12 months. In addition, 57.75% (648/1122)
      patients with mumps were children aged 5-9 years, and 50.54% (94/186) rubella
      cases were aged 15-39 years. CONCLUSIONS: A timely two-dose MMR vaccination
      schedule is recommended, with the first dose at 8 months and the second dose at
      18-24 months. An MR vaccination speed-up campaign may be necessary for elder
      adolescents and young adults, particularly young females.

PMID- 24586719
TI  - Growth of Caiman crocodilus yacare in the Brazilian Pantanal.
AB  - We studied growth of the caiman, Caiman crocodilus yacare, in the Brazilian
      Pantanal for 27 years between 1987 and 2013.We recaptured 647 of 7769 C. c.
      yacare initially marked in an area of 50 km(2), in two ranches. We were able to
      determine size at age accurately for 24 male and17 female caimans that had been
      marked at hatching or less than 1 year old, and recaptured over periods of 5 to
      24 years. The other 606 caimans were used to evaluate short-term growth rates.
      Age-size relationships were estimated using growth models from the Richards
      family of curves (full model, von Bertalanffy and monomolecular). The form of the
      relationships differed between analyses based on caimans of known age and
      analyses based on integration of growth rate on size relationships for caimans
      whose ages were not known. Individuals showed large variation in short-term
      growth rates, but data on known-age animals indicated little between-individual
      variability in long-term growth rates. There was evidence of a small effect of
      rainfall, but not temperature, on short-term growth of small caimans, but most
      variation in growth rates was unexplained by variables other than age and sex.
      Data on known-age individuals indicated that female C. c. yacare generally reach
      sexual maturity between 10 and 15 years of age. Because of the asymptotic
      relationship between age and size, deviations of observations from the model for
      age are larger than for size, and estimates of age at a given size have greater
      errors than estimates of size at a given age. Integration of growth rate on size
      relationships may be adequate for estimating size from age in many cases, but
      accurate estimates of age from size require data on known-age individuals over
      the size range of the species. 

PMID- 24586718
TI  - Self-reported musculoskeletal disorders of the distal upper extremities and the
      neck in German veterinarians: a cross-sectional study.
AB  - BACKGROUND: Veterinary work is a physically demanding profession and entails the
      risk of injuries and diseases of the musculoskeletal system, particularly in the
      upper body. The prevalence of musculoskeletal disorders (MSD), the consequences
      and work-related accidents in German veterinarians were investigated. Work
      related and individual factors associated with MSD of upper extremities and the
      neck were analyzed. METHODS: In 2011, a self-reporting Standardized Nordic
      Questionnaire was mailed to registered veterinarians in seven federal medical
      associations in Germany. A total of 3174 (38.4%) veterinarians responded.
      Logistic regression analysis was used to determine the association between risk
      factors and MSD-related impairment of daily activities. RESULTS: MSD in the neck
      (66.6%) and shoulder (60.5%) were more prevalent than in the hand (34.5%) or
      elbow (24.5%). Normal activities were affected in 28.7% (neck), 29.5% (shoulder),
      19.4% (hand) and 14% (elbow) of the respondents. MSD in the upper body occurred
      significantly more often in large animal practitioners. Accidents that resulted
      in MSD were most frequently reported in the hand/wrist (14.3%) or in the shoulder
      (10.8%). The majority of all accidents in the distal upper extremities were
      caused by animals than by other factors (19% vs. 9.2%). For each area of the
      body, a specific set of individual and work-related factors contributed
      significantly to severe MSD: Older age, gender, previous injuries, BMI, practice
      type, veterinary procedures such as dentistry, rectal procedures and obstetric
      procedures as well as high demands and personal burnout. CONCLUSION: From the
      perspective of occupational health and safety, it seems to be necessary to
      improve accident prevention and to optimize the ergonomics of specific tasks. Our
      data suggest the need for target group-specific preventive measures that also
      focus on the psychological factors at work.

PMID- 24586720
TI  - Soil organic carbon and total nitrogen gains in an old growth deciduous forest in
      Germany.
AB  - Temperate forests are assumed to be organic carbon (OC) sinks, either because of
      biomass increases upon elevated CO2 in the atmosphere and large nitrogen
      deposition, or due to their age structure. Respective changes in soil OC and
      total nitrogen (TN) storage have rarely been proven. We analysed OC, TN, and bulk
      densities of 100 soil cores sampled along a regular grid in an old-growth
      deciduous forest at the Hainich National Park, Germany, in 2004 and again in
      2009. Concentrations of OC and TN increased significantly from 2004 to 2009,
      mostly in the upper 0-20 cm of the mineral soil. Changes in the fine earth masses
      per soil volume impeded the detection of OC changes based on fixed soil volumes.
      When calculated on average fine earth masses, OC stocks increased by 323 +/- 146
      g m(-2) and TN stocks by 39 +/- 10 g m(-2) at 0-20 cm soil depth from 2004 to
      2009, giving average annual accumulation rates of 65 +/- 29 g OC m(-2) yr(-1) and
      7.8 +/- 2 g N m(-2) yr(-1). Accumulation rates were largest in the upper part of
      the B horizon. Regional increases in forest biomass, either due to recovery of
      forest biomass from previous forest management or to fertilization by elevated
      CO2 and N deposition, are likely causes for the gains in soil OC and TN. As TN
      increased stronger (1.3% yr(-1) of existing stocks) than OC (0.9% yr(-1)), the OC
      to-TN ratios declined significantly. Results of regression analyses between
      changes in OC and TN stocks suggest that at no change in OC, still 3.8 g TN m(-2)
      yr(-1) accumulated. Potential causes for the increase in TN in excess to OC are
      fixation of inorganic N by the clay-rich soil or changes in microbial
      communities. The increase in soil OC corresponded on average to 6-13% of the
      estimated increase in net biome productivity.

PMID- 24586721
TI  - Dietary quercetin supplementation in mice increases skeletal muscle PGC1alpha
      expression, improves mitochondrial function and attenuates insulin resistance in
      a time-specific manner.
AB  - AIMS/HYPOTHESIS: High fat diet (HFD)-induced insulin resistance (IR) is partially
      characterized by reduced skeletal muscle mitochondrial function and peroxisome
      proliferator activated receptor gamma coactivator 1 alpha (PGC1alpha) expression.
      Our previous study showed that a high dose of the bioflavonoid quercetin
      exacerbated HFD-induced IR; yet, others have demonstrated that quercetin improves
      insulin sensitivity. The aim of this study was to investigate whether differing
      doses of quercetin act in a time-dependent manner to attenuate HFD-induced IR in
      association with improved skeletal muscle mitochondrial function and PGC1alpha
      expression. METHODS: C57BL/6J mice were fed HFD for 3 or 8 wks, with or without a
      low (50 ug/day; HF+50Q) or high (600 ug/day, HF+600Q) dose of quercetin. Whole
      body and metabolic phenotypes and insulin sensitivity were assessed. Skeletal
      muscle metabolomic analysis of acylcarnitines and PGC1alpha mRNA expression via
      qRT-PCR were measured. RESULTS: Quercetin at 50 ug/day for 8 wk attenuated HFD
      induced increases in fat mass, body weight and IR and increased PGC1alpha
      expression, whereas 600 ug/day of quercetin exacerbated fat mass accumulation
      without altering body weight, IR or PGC1alpha. PGC1alpha expression correlated
      with acylcarnitine levels similarly in HF and HF+600Q; these correlations were
      not present in HF+50Q. At both time points, energy expenditure increased in
      HF+50Q and decreased in HF+600Q, independent of PGC1alpha and IR.
      CONCLUSIONS/INTERPRETATION: Chronic dietary quercetin supplementation at low but
      not higher dose ameliorates the development of diet-induced IR while increasing
      PGC1alpha expression in muscle, suggesting that skeletal muscle may be an
      important target for the insulin-sensitizing effects of a low dose of quercetin.

PMID- 24586722
TI  - Tropheryma whipplei, the agent of Whipple's disease, affects the early to late
      phagosome transition and survives in a Rab5- and Rab7-positive compartment.
AB  - Tropheryma whipplei, the agent of Whipple's disease, inhibits phago-lysosome
      biogenesis to create a suitable niche for its survival and replication in
      macrophages. To understand the mechanism by which it subverts phagosome
      maturation, we used biochemical and cell biological approaches to purify and
      characterise the intracellular compartment where Tropheryma whipplei resides
      using mouse bone-marrow-derived macrophages. We showed that in addition to Lamp
      1, the Tropheryma whipplei phagosome is positive for Rab5 and Rab7, two GTPases
      required for the early to late phagosome transition. Unlike other pathogens,
      inhibition of PI(3)P production was not the mechanism for Rab5 stabilisation at
      the phagosome. Overexpression of the inactive, GDP-bound form of Rab5 bypassed
      the pathogen-induced blockade of phago-lysosome biogenesis. This suggests that
      Tropheryma whipplei blocks the switch from Rab5 to Rab7 by acting on the Rab5
      GTPase cycle. A bio-informatic analysis of the Tropheryma whipplei genome
      revealed a glyceraldehyde-3-phosphate dehydrogenase (GAPDH) homologous with the
      GAPDH of Listeria monocytogenes, and this may be the bacterial protein
      responsible for blocking Rab5 activity. To our knowledge, Tropheryma whipplei is
      the first pathogen described to induce a "chimeric" phagosome stably expressing
      both Rab5 and Rab7, suggesting a novel and specific mechanism for subverting
      phagosome maturation. 

PMID- 24586724
TI  - Aquatic respiration rate measurements at low oxygen concentrations.
AB  - Despite its huge ecological importance, microbial oxygen respiration in pelagic
      waters is little studied, primarily due to methodological difficulties.
      Respiration measurements are challenging because of the required high resolution
      of oxygen concentration measurements. Recent improvements in oxygen sensing
      techniques bear great potential to overcome these limitations. Here we compare 3
      different methods to measure oxygen consumption rates at low oxygen
      concentrations, utilizing amperometric Clark type sensors (STOX), optical sensors
      (optodes), and mass spectrometry in combination with (18-18)O2 labeling. Oxygen
      concentrations and consumption rates agreed well between the different methods
      when applied in the same experimental setting. Oxygen consumption rates between
      30 and 400 nmol L(-1) h(-1) were measured with high precision and relative
      standard errors of less than 3%. Rate detection limits in the range of 1 nmol L(
      1) h(-1) were suitable for rate determinations in open ocean water and were
      lowest at the lowest applied O2 concentration. 

PMID- 24586723
TI  - A prospective study on metabolic risk factors and gallbladder cancer in the
      metabolic syndrome and cancer (Me-Can) collaborative study.
AB  - OBJECTIVE: To investigate the association between metabolic risk factors
      (individually and in combination) and risk of gallbladder cancer (GBC). METHODS:
      The metabolic syndrome and cancer project (Me-Can) includes cohorts from Norway,
      Austria, and Sweden with data on 578,700 men and women. We used Cox proportional
      hazard regression models to calculate relative risks of GBC by body mass index
      (BMI), blood pressure, and plasma levels of glucose, cholesterol, and
      triglycerides as continuous standardised variables and their standardised sum of
      metabolic syndrome (MetS) z-score. The risk estimates were corrected for random
      error in measurements. RESULTS: During an average follow-up of 12.0 years (SD =
      7.8), 184 primary gallbladder cancers were diagnosed. Relative risk of
      gallbladder cancer per unit increment of z-score adjusted for age, smoking status
      and BMI (except for BMI itself) and stratified by birth year, sex and sub
      cohorts, was for BMI 1.31 (95% confidence interval 1.11, 1.57) and blood glucose
      1.76 (1.10, 2.85). Further analysis showed that the effect of BMI on GBC risk is
      larger among women in the premenopausal age group (1.84 (1.23, 2.78)) compared to
      those in the postmenopausal age group (1.29 (0.93, 1.79)). For the other
      metabolic factors no significant association was found (mid blood pressure 0.96
      (0.71, 1.31), cholesterol 0.84 (0.66, 1.06) and serum triglycerides 1.16 (0.82,
      1.64)). The relative risk per one unit increment of the MetS z-score was 1.37
      (1.07, 1.73). CONCLUSION: This study showed that increasing BMI and impaired
      glucose metabolism pose a possible risk for gallbladder cancer. Beyond the
      individual factors, the results also showed that the metabolic syndrome as an
      entity presents a risk constellation for the occurrence of gallbladder cancer.

PMID- 24586725
TI  - Ultraviolet light enhances the bovine serum albumin fixation for acid fast
      bacilli stain.
AB  - The use of a liquid culture system such as MGIT broth has greatly improved the
      sensitivity of isolating mycobacteria in clinical laboratories. Microscopic
      visualization of acid fast bacilli (AFB) in the culture positive MGIT broth
      remains the first routine step for rapidly indicating the presence of
      mycobacteria. We modified an ultraviolet (UV) light fixation process to increase
      AFB cells adherence to the slide. The retained haze proportion of a 1-cm circle
      marked area on the smear slide was quantified after the staining procedure
      indicating the adherence degree of AFB cells. More AFB cells were preserved on
      the slide after exposure to UV light of either germicidal lamp or UV crosslinker
      in a time-dependent manner. We demonstrated both the bovine serum albumin (BSA)
      in MGIT media and UV light exposure were required for enhancing fixation of AFB
      cells. While applying to AFB stains for 302 AFB positive MGIT broths in clinics,
      more AFB cells were retained and observed on smear slides prepared by the
      modified fixation procedure rather than by the conventional method. The modified
      fixation procedure was thus recommended for improving the sensitivity of
      microscopic diagnosis of AFB cells in culture positive MGIT broth. 

PMID- 24586727
TI  - Engineering Synechocystis PCC6803 for hydrogen production: influence on the
      tolerance to oxidative and sugar stresses.
AB  - In the prospect of engineering cyanobacteria for the biological photoproduction
      of hydrogen, we have studied the hydrogen production machine in the model
      unicellular strain Synechocystis PCC6803 through gene deletion, and
      overexpression (constitutive or controlled by the growth temperature). We
      demonstrate that the hydrogenase-encoding hoxEFUYH operon is dispensable to
      standard photoautotrophic growth in absence of stress, and it operates in cell
      defense against oxidative (H2O2) and sugar (glucose and glycerol) stresses.
      Furthermore, we showed that the simultaneous over-production of the proteins
      HoxEFUYH and HypABCDE (assembly of hydrogenase), combined to an increase in
      nickel availability, led to an approximately 20-fold increase in the level of
      active hydrogenase. These novel results and mutants have major implications for
      those interested in hydrogenase, hydrogen production and redox metabolism, and
      their connections with environmental conditions.

PMID- 24586726
TI  - Age-related weakness of proximal muscle studied with motor cortical mapping: a
      TMS study.
AB  - Aging-related weakness is due in part to degeneration within the central nervous
      system. However, it is unknown how changes to the representation of corticospinal
      output in the primary motor cortex (M1) relate to such weakness. Transcranial
      magnetic stimulation (TMS) is a noninvasive method of cortical stimulation that
      can map representation of corticospinal output devoted to a muscle. Using TMS, we
      examined age-related alterations in maps devoted to biceps brachii muscle to
      determine whether they predicted its age-induced weakness. Forty-seven right
      handed subjects participated: 20 young (22.6 +/- 0.90 years) and 27 old (74.96 +/
      1.35 years). We measured strength as force of elbow flexion and
      electromyographic activation of biceps brachii during maximum voluntary
      contraction. Mapping variables included: 1) center of gravity or weighted mean
      location of corticospinal output, 2) size of map, 3) volume or excitation of
      corticospinal output, and 4) response density or corticospinal excitation per
      unit area. Center of gravity was more anterior in old than in young (p<0.001),
      though there was no significant difference in strength between the age groups.
      Map size, volume, and response density showed no significant difference between
      groups. Regardless of age, center of gravity significantly predicted strength
      (beta = -0.34, p = 0.005), while volume adjacent to the core of map predicted
      voluntary activation of biceps (beta = 0.32, p = 0.008). Overall, the anterior
      shift of the map in older adults may reflect an adaptive change that allowed for
      the maintenance of strength. Laterally located center of gravity and higher
      excitation in the region adjacent to the core in weaker individuals could reflect
      compensatory recruitment of synergistic muscles. Thus, our study substantiates
      the role of M1 in adapting to aging-related weakness and subtending strength and
      muscle activation across age groups. Mapping from M1 may offer foundation for an
      examination of mechanisms that preserve strength in elderly.

PMID- 24586728
TI  - Decrypting cryptogenic hepatocellular carcinoma: clinical manifestations,
      prognostic factors and long-term survival by propensity score model.
AB  - BACKGROUND AND AIMS: The clinical aspects of cryptogenic hepatocellular carcinoma
      (HCC), defined as HCC in patients without hepatitis B, C or alcoholism, are not
      clear. We investigated its clinical presentations, long-term survival and
      prognostic predictors. METHODS: A total of 2645 HCC patients were studied. One-to
      one matched pairs between viral/alcoholic and cryptogenic HCC patients were
      generated by using the propensity model. The survival analysis was performed with
      the Kaplan-Meier method and log-rank test, and hazard ratios were calculated with
      Cox proportional hazards model. RESULTS: Among 366 (14%) patients with
      cryptogenic HCC, 34% of patients were presented with abdominal discomfort, and
      31% of patients were identified incidentally. Compared to patients with
      viral/alcoholic HCC, cryptogenic HCC patients were significantly older
      (p<0.0001), with poorer performance status (p = 0.0031) and less often underwent
      curative treatment (p = 0.0041). They also had larger tumor burden (p<0.0001),
      poorer renal function (p<0.0001), lower alpha-fetoprotein level (p<0.0001), and
      more advanced Barcelona Clinic Liver Cancer stages (p<0.0001). With propensity
      score model, 366 pairs of similar HCC patients were selected and similar long
      term survival between the two groups of patients was found (p = 0.1038). For
      cryptogenic HCC patients, alpha-fetoprotein ?49 ng/mL (hazard ratio [HR]: 1.955,
      p = 0.0002), Child-Turcotte-Pugh class B/C (HR: 2.798, p<0.0001), performance
      status ?1 (HR: 2.463, p<0.0001) and vascular invasion (HR: 1.608, p = 0.0257)
      were independent predictors of poor prognosis. CONCLUSIONS: Patients with
      cryptogenic HCC are usually diagnosed with poor general condition at late stages.
      However, cryptogenic HCC patients have similar prognostic predictors and long
      term survival compared with viral/alcoholic HCC patients. Diagnosis at an early
      stage may improve their clinical outcomes.

PMID- 24586729
TI  - Catalytic signature of a heat-stable, chimeric human alkaline phosphatase with
      therapeutic potential.
AB  - Recombinant alkaline phosphatases are becoming promising protein therapeutics to
      prevent skeletal mineralization defects, inflammatory bowel diseases, and treat
      acute kidney injury. By substituting the flexible crown domain of human
      intestinal alkaline phosphatase (IAP) with that of the human placental isozyme
      (PLAP) we generated a chimeric enzyme (ChimAP) that retains the structural
      folding of IAP, but displays greatly increased stability, active site Zn2+
      binding, increased transphosphorylation, a higher turnover number and narrower
      substrate specificity, with comparable selectivity for bacterial
      lipopolysaccharide (LPS), than the parent IAP isozyme. ChimAP shows promise as a
      protein therapeutic for indications such as inflammatory bowel diseases, gut
      dysbioses and acute kidney injury.

PMID- 24586730
TI  - Genome-wide methylation analyses in glioblastoma multiforme.
AB  - Few studies had investigated genome-wide methylation in glioblastoma multiforme
      (GBM). Our goals were to study differential methylation across the genome in gene
      promoters using an array-based method, as well as repetitive elements using
      surrogate global methylation markers. The discovery sample set for this study
      consisted of 54 GBM from Columbia University and Case Western Reserve University,
      and 24 brain controls from the New York Brain Bank. We assembled a validation
      dataset using methylation data of 162 TCGA GBM and 140 brain controls from dbGAP.
      HumanMethylation27 Analysis Bead-Chips (Illumina) were used to interrogate 26,486
      informative CpG sites in both the discovery and validation datasets. Global
      methylation levels were assessed by analysis of L1 retrotransposon (LINE1), 5
      methyl-deoxycytidine (5m-dC) and 5 hydroxylmethyl-deoxycytidine (5hm-dC) in the
      discovery dataset. We validated a total of 1548 CpG sites (1307 genes) that were
      differentially methylated in GBM compared to controls. There were more than twice
      as many hypomethylated genes as hypermethylated ones. Both the discovery and
      validation datasets found 5 tumor methylation classes. Pathway analyses showed
      that the top ten pathways in hypomethylated genes were all related to functions
      of innate and acquired immunities. Among hypermethylated pathways,
      transcriptional regulatory network in embryonic stem cells was the most
      significant. In the study of global methylation markers, 5m-dC level was the best
      discriminant among methylation classes, whereas in survival analyses, high level
      of LINE1 methylation was an independent, favorable prognostic factor in the
      discovery dataset. Based on a pathway approach, hypermethylation in genes that
      control stem cell differentiation were significant, poor prognostic factors of
      overall survival in both the discovery and validation datasets. Approaches that
      targeted these methylated genes may be a future therapeutic goal. 

PMID- 24586731
TI  - In vivo generation of immature inner hair cells in neonatal mouse cochleae by
      ectopic Atoh1 expression.
AB  - Regeneration of auditory hair cells (HCs) is a promising approach to restore
      hearing. Recent studies have demonstrated that induced pluripotent stem
      cells/embryonic stem cells or supporting cells (SCs) adjacent to HCs can be
      converted to adopt the HC fate. However, little is known about whether new HCs
      are characteristic of outer or inner HCs. Here, we showed in vivo conversion of 2
      subtypes of SCs, inner border cells (IBs) and inner phalangeal cells (IPhs), to
      the inner HC (IHC) fate. This was achieved by ectopically activating Atoh1, a
      transcription factor necessary for HC fate, in IBs/IPhs at birth. Atoh1+ IBs/IPhs
      first turned on Pou4f3, another HC transcription factor, before expressing 8 HC
      markers. The conversion rate gradually increased from ~ 2.4% at 1 week of age to
      ~ 17.8% in adult. Interestingly, new HCs exhibited IHC characteristics such as
      straight line-shaped stereociliary bundles, expression of Fgf8 and otoferlin, and
      presence of larger outward currents than those of outer HCs. However, new HCs
      lacked the terminal differentiation IHC marker vGlut3, exhibited reduced density
      of presynaptic Cbtp2 puncta that had little postsynaptic GluR2 specialization,
      and displayed immature IHC outward currents. Our results demonstrate that the
      conversion rate of IBs/IPhs in vivo by Atoh1 ectopic expression into the IHC fate
      was higher and faster and the conversion was more complete than that of the 2
      other SC subtypes underneath the outer HCs; however, these new IHCs are arrested
      before terminal differentiation. Thus, IBs/IPhs are good candidates to regenerate
      IHCs in vivo.

PMID- 24586732
TI  - Do the ticks of birds at an important migratory hotspot reflect the seasonal
      dynamics of Ixodes ricinus at the migration initiation site? A case study in the
      Danube Delta.
AB  - Migratory birds play important roles as distributors of ticks within and between
      continents. In the Old World, the most important migratory route of birds links
      Asia, Europe and Africa. During their migration, birds use various stopover
      sites, where they feed and rest and where ticks may attach or detach, creating
      new natural foci for vector-borne diseases. Danube Delta is one of the most
      important migration hotspots and so far no studies were focused on ticks of
      migratory birds herein. The aim of the present study was to assess the species
      diversity and seasonal dynamics of ticks parasitizing migratory birds in Danube
      Delta Biosphere Reserve. Migratory birds were trapped on Grindul Lupilor (44
      degrees 41'N; 28 degrees 56'E) using mist nets during 4 migratory seasons (2
      spring and 2 autumn) in 2011 and 2012. From each bird, all the ticks were
      collected and identified based on morphological features. Epidemiological
      parameters (prevalence, mean abundance, mean intensity) were calculated and all
      data were analysed statistically based on the season (spring and autumn),
      regional status of birds (migrants and breeding) and foraging behaviour (ground
      feeders, reed-bed feeders, foliage feeders). A total of 1434 birds (46 species)
      were captured. Ticks were found on 94 birds (10 species). Significantly more
      migratory birds hosted ticks, compared to resident birds. The 400 collected ticks
      belonged to four species: Ixodes ricinus (92.25%), I. arboricola (6.25%), I.
      redikorzevi (1.00%) and Haemaphysalis punctata (0.50%). A higher prevalence was
      found for I. ricinus in spring, with higher prevalence of nymphs in this season,
      while larvae occurred with the same prevalence in both seasons. Larval intensity
      was higher during spring and nymphs were more abundant during autumn. The
      seasonal differences in our study may be related not to the local seasonal
      dynamics of ticks, but on the seasonal dynamics at the site of migration
      initiation. 

PMID- 24586733
TI  - Premature CD4+ T cell aging and its contribution to lymphopenia-induced
      proliferation of memory cells in autoimmune-prone non-obese diabetic mice.
AB  - Lymphopenia-induced proliferation (LIP), a mechanism to maintain a constant
      number of T cells in circulation, occurs in both normal aging and autoimmune
      disease. The incidence of most autoimmune diseases increases with age, and
      premature CD4(+) T cell aging has been reported in several autoimmune diseases.
      In this study, we tested the hypothesis that premature CD4(+) T cell aging can
      cause autoimmune disease by examining whether premature CD4(+) T cell aging
      exists and causes LIP in our mouse model. Non-obese diabetic (NOD) mice were used
      because, in addition to Treg defects, the LIP of T cells has been shown to plays
      a causative role in the development of insulin-dependent diabetes mellitus (IDDM)
      in these mice. We found that with advancing age, NOD mice exhibited an
      accelerated decrease in the number of CD4(+) T cells due to the loss of naive
      cells. This was accompanied by an increase in the percentage of memory cells,
      leading to a reduced naive/memory ratio. In addition, both the percentage of
      CD28(+) cells in CD4(+) T cells and IL-2 production decreased, while the
      percentage of FAS(+)CD44(+) increased, suggesting that NOD mice exhibit premature
      CD4(+) T cell aging. This process preferentially contributed to LIP of memory
      cells. Therefore, our results suggest that premature CD4(+) T cell aging
      underlies the development of IDDM in NOD mice. Given that CD28 and IL-2 play
      important roles in Treg function, the relationships between premature CD4(+) T
      cell aging and lymphopenia as well as Treg defects in autoimmune-prone NOD mice
      are proposed. 

PMID- 24586734
TI  - Estimating dose painting effects in radiotherapy: a mathematical model.
AB  - Tumor heterogeneity is widely considered to be a determinant factor in tumor
      progression and in particular in its recurrence after therapy. Unfortunately,
      current medical techniques are unable to deduce clinically relevant information
      about tumor heterogeneity by means of non-invasive methods. As a consequence,
      when radiotherapy is used as a treatment of choice, radiation dosimetries are
      prescribed under the assumption that the malignancy targeted is of a homogeneous
      nature. In this work we discuss the effects of different radiation dose
      distributions on heterogeneous tumors by means of an individual cell-based model.
      To that end, a case is considered where two tumor cell phenotypes are present,
      which we assume to strongly differ in their respective cell cycle duration and
      radiosensitivity properties. We show herein that, as a result of such
      differences, the spatial distribution of the corresponding phenotypes, whence the
      resulting tumor heterogeneity can be predicted as growth proceeds. In particular,
      we show that if we start from a situation where a majority of ordinary cancer
      cells (CCs) and a minority of cancer stem cells (CSCs) are randomly distributed,
      and we assume that the length of CSC cycle is significantly longer than that of
      CCs, then CSCs become concentrated at an inner region as tumor grows. As a
      consequence we obtain that if CSCs are assumed to be more resistant to radiation
      than CCs, heterogeneous dosimetries can be selected to enhance tumor control by
      boosting radiation in the region occupied by the more radioresistant tumor cell
      phenotype. It is also shown that, when compared with homogeneous dose
      distributions as those being currently delivered in clinical practice, such
      heterogeneous radiation dosimetries fare always better than their homogeneous
      counterparts. Finally, limitations to our assumptions and their resulting
      clinical implications will be discussed. 

PMID- 24586736
TI  - Comparison of the 'chemical' and 'structural' approaches to the optimization of
      the thrombin-binding aptamer.
AB  - Noncanonically structured DNA aptamers to thrombin were examined. Two different
      approaches were used to improve stability, binding affinity and biological
      activity of a known thrombin-binding aptamer. These approaches are chemical
      modification and the addition of a duplex module to the aptamer core structure.
      Several chemically modified aptamers and the duplex-bearing ones were all studied
      under the same conditions by a set of widely known and some relatively new
      methods. A number of the thrombin-binding aptamer analogs have demonstrated
      improved characteristics. Most importantly, the study allowed us to compare
      directly the two approaches to aptamer optimization and to analyze their relative
      advantages and disadvantages as well as their potential in drug design and
      fundamental studies. 

PMID- 24586735
TI  - Event-related alpha suppression in response to facial motion.
AB  - While biological motion refers to both face and body movements, little is known
      about the visual perception of facial motion. We therefore examined alpha wave
      suppression as a reduction in power is thought to reflect visual activity, in
      addition to attentional reorienting and memory processes. Nineteen neurologically
      healthy adults were tested on their ability to discriminate between successive
      facial motion captures. These animations exhibited both rigid and non-rigid
      facial motion, as well as speech expressions. The structural and surface
      appearance of these facial animations did not differ, thus participants decisions
      were based solely on differences in facial movements. Upright, orientation
      inverted and luminance-inverted facial stimuli were compared. At occipital and
      parieto-occipital regions, upright facial motion evoked a transient increase in
      alpha which was then followed by a significant reduction. This finding is
      discussed in terms of neural efficiency, gating mechanisms and neural
      synchronization. Moreover, there was no difference in the amount of alpha
      suppression evoked by each facial stimulus at occipital regions, suggesting early
      visual processing remains unaffected by manipulation paradigms. However, upright
      facial motion evoked greater suppression at parieto-occipital sites, and did so
      in the shortest latency. Increased activity within this region may reflect higher
      attentional reorienting to natural facial motion but also involvement of areas
      associated with the visual control of body effectors. 

PMID- 24586738
TI  - Lethal fighting in nematodes is dependent on developmental pathway: male-male
      fighting in the entomopathogenic nematode Steinernema longicaudum.
AB  - Aggressive encounters occur between competitors (particularly males) throughout
      the animal kingdom, and in some species can result in severe injury and death.
      Here we describe for the first time lethal interactions between male nematodes
      and provide evidence that the expression of this behaviour is developmentally
      controlled. Males of the entomopathogenic nematode Steinernema longicaudum coil
      around each other, resulting in injuries, paralysis and frequently death. The
      probability of death occurring between pairs of males was affected by the
      developmental pathway followed, being much greater among males that had passed
      through the infective juvenile (IJ, or dauer) stage than among males that had
      not. Post-IJ males are found only in newly colonised hosts, typically with few
      competing males present. Killing those few competitors may secure valuable
      resources (both females and a host cadaver for nourishment of offspring). Non-IJ
      males develop in subsequent generations within a host cadaver, where the presence
      of many closely related male competitors increases the risk:benefit ratio of
      fighting. Thus, passage through the IJ stage primes males for enhanced aggression
      in circumstances where this is more likely to result in increased reproductive
      success. Fighting occurred between males developing in mixed-sex social groups,
      indicating that it is an evolved trait and not an abnormal response to absence of
      females. This is supported by finding high mortality of males, but not of
      females, across a range of population densities in insect cadavers. We propose
      that these nematodes, with their relatively simple organization, may be a useful
      model for studies of aggression. 

PMID- 24586737
TI  - Loss of genetic diversity among ocelots in the United States during the 20th
      century linked to human induced population reductions.
AB  - Ocelots (Leopardus pardalis) in the United States currently exhibit low levels of
      genetic diversity. One hypothesis for this observation is that habitat
      fragmentation, resulting from human induced changes in the landscape during the
      20(th) century, created island populations with highly reduced gene flow and
      increased genetic drift and inbreeding. In an effort to investigate this, we used
      a portion of the mitochondrial control region and 11 autosomal microsatellite
      loci to examine historical levels of genetic diversity and infer temporal changes
      in ocelot populations between 1853 and 2005. Levels of genetic diversity were
      higher in historical ocelot populations than in extant populations from Texas.
      The earliest documented loss of mitochondrial haplotype diversity occurred at
      Laguna Atascosa National Wildlife Refuge. The second extant population inhabiting
      private lands in Willacy County retained higher levels of genetic diversity
      through the 1990s, but subsequently lost diversity over the next decade. A
      similar pattern was observed for autosomal microsatellite loci. This supports the
      argument that low levels of genetic diversity in Texas are related to human
      induced population reductions and fragmentation, both of which threaten the
      remaining ocelots in the United States. At this time, the best means of
      mitigating the continued erosion of genetic variation are translocation of
      individuals either from larger populations in Mexico to Texas, or between the
      Texas populations. 

PMID- 24586739
TI  - Increased risk of stroke after septicaemia: a population-based longitudinal study
      in Taiwan.
AB  - Inflammation and infection have been noted to increase stroke risk. However, the
      association between septicaemia and increased risk of stroke remains unclear.
      This population-based cohort study, using a National Health Insurance database,
      aimed to investigate whether patients with septicaemia are predisposed to
      increased stroke risk. The study included all patients hospitalised for
      septicaemia for the first time between 2000 and 2003 without prior stroke.
      Patients were followed until the end of 2010 to evaluate incidence of stroke. An
      age-, gender- and co-morbidities-matched cohort without prior stroke served as
      the control. Cox's proportional hazards regressions were used to assess
      differences in stroke risk between groups. Based on hazard ratios (HRs), patients
      with septicaemia had greater stroke risk, especially in the younger age groups
      (age <45: HR = 4.16, 95% CI: 2.39-7.24, p<0.001; age 45-64: HR = 1.76, 95% CI:
      1.41-2.19, p<0.001; age >= 65: HR = 1.05, 95% CI: 0.91-1.22, p>0.05).
      Haemorrhagic stroke was the dominant type (ischaemic stroke: HR = 1.20, 95% CI:
      1.06-1.37, p<0.01; haemorrhagic stroke: HR = 1.82, 95% CI: 1.35-2.46, p<0.001)
      and patients without co-morbidities were at slightly higher risk (without co
      morbidities: HR = 1.49, 95% CI: 1.02-2.17, p<0.05; with co-morbidities: HR =
      1.24, 95% CI: 1.10-1.41, p<0.001). The impact of septicaemia on stroke risk was
      highest within 6 months of the event and gradually declined over time. Our
      results suggest that septicaemia is associated with an increase in stroke risk,
      which is greatest in haemorrhagic stroke. Closer attention to patients with
      history of septicaemia may be warranted for stroke preventive measures,
      especially for younger patients without co-morbidities.

PMID- 24586740
TI  - betanu integrin inhibits chronic and high level activation of JNK to repress
      senescence phenotypes in Drosophila adult midgut.
AB  - Proper control of adult stem cells including their proliferation and
      differentiation is crucial in maintaining homeostasis of well-organized
      tissues/organs throughout an organism's life. The Drosophila adult midgut has
      intestinal stem cells (ISCs), which have been exploited as a simple model system
      to investigate mechanisms controlling adult tissue homeostasis. Here, we found
      that a viable mutant of betanu integrin (betaint-nu), encoding one of two
      Drosophila integrin beta subunits, showed a short midgut and abnormal
      multilayered epithelia accompanied by an increase in ISC proliferation and
      misdifferentiation defects. The increase in ISC proliferation and
      misdifferentiation was due to frequent ISC duplication expanding a pool of ISCs,
      which was caused by depression of the Notch signalling, and up-regulation of
      unpaired (upd), a gene encoding an extracellular ligand in the JAK/STAT
      signalling pathway. In addition, we observed that abnormally high accumulation of
      filamentous actin (F-actin) was caused in the betaint-nu mutant enterocytes.
      Furthermore, the defects were rescued by suppressing c-Jun N-terminal kinase
      (JNK) signalling, which was up-regulated in a manner correlated with the defect
      levels in the above-mentioned betaint-nu mutant phenotype. These symptoms
      observed in young betaint-nu mutant midgut were very similar to those in the aged
      midgut in wild type. Our results suggested that betaint-nu has a novel function
      for the Drosophila adult midgut homeostasis under normal conditions and provided
      a new insight into possible age-related diseases caused by latent abnormality of
      an integrin function. 

PMID- 24586741
TI  - FBXW7 mutations in patients with advanced cancers: clinical and molecular
      characteristics and outcomes with mTOR inhibitors.
AB  - PURPOSE: FBXW7 is a tumor suppressor gene responsible for the degradation of
      several proto-oncogenes. Preclinical data suggest that FBXW7 mutations sensitize
      cells to mTOR inhibitors. Clinicopathologic characteristics of cancer patients
      with FBXW7 mutations and their responses to mTOR inhibitors remain unknown.
      METHODS: Using multiplex gene panels we evaluated how the FBXW7 mutation affected
      the cancer phenotype of patients referred to a phase I clinic starting January
      2012. Whenever possible patients positive for FBXW7 mutation were treated with
      regimens containing an mTOR inhibitors and their outcomes were reviewed. RESULTS:
      FBXW7 mutations were detected in 17 of 418 patients (4.0%). Among tumor types
      with more than 10 patients tested, FBXW7 mutations occurred in colorectal cancer
      (7/49; 14.3%), squamous cell cancer of head and neck (2/18; 11.1%), liver (1/13;
      7.7%), and ovarian cancers (1/40; 2.5%). No one clinical, pathological or
      demographic feature was characteristic of the FBXW7-mutated patient population.
      The mutation occurred in isolation in only 2/17 (12%) patients, and KRAS was
      frequently found as a concomitant mutation, especially in patients with
      colorectal cancer (6/7; 86%). Ten patients were treated on a protocol containing
      an mTOR inhibitor, with a median time to treatment failure of 2.8 months (range,
      1.3-6.8). One patient with liver cancer (fibrolamellar subtype) continues to have
      a prolonged stable disease for 6.8+ months. CONCLUSION: In patients with advanced
      cancers, somatic mutations in FBXW7 usually occur with other simultaneous
      molecular aberrations, which can contribute to limited therapeutic efficacy of
      mTOR inhibitors.

PMID- 24586742
TI  - Effect of age and biological subtype on the risk and timing of brain metastasis
      in breast cancer patients.
AB  - BACKGROUND: Brain metastasis is a major complication of breast cancer. This study
      aimed to analyze the effect of age and biological subtype on the risk and timing
      of brain metastasis in breast cancer patients. PATIENTS AND METHODS: We
      identified subtypes of invasive ductal carcinoma of the breast by determining
      estrogen receptor, progesterone receptor and HER2 status. Time to brain
      metastasis according to age and cancer subtype was analyzed by Cox proportional
      hazard analysis. RESULTS: Of the 2248 eligible patients, 164 (7.3%) developed
      brain metastasis over a median follow-up of 54.2 months. Age 35 or younger, HER2
      enriched subtype, and triple-negative breast cancer were significant risk factors
      of brain metastasis. Among patients aged 35 or younger, the risk of brain
      metastasis was independent of biological subtype (P = 0.507). Among patients aged
      36-59 or >60 years, those with triple-negative or HER2-enriched subtypes had
      consistently increased risk of brain metastasis, as compared with those with
      luminal A tumors. Patients with luminal B tumors had higher risk of brain
      metastasis than luminal A only in patients >60 years. CONCLUSIONS: Breast cancer
      subtypes are associated with differing risks of brain metastasis among different
      age groups. Patients age 35 or younger are particularly at risk of brain
      metastasis independent of biological subtype.

PMID- 24586743
TI  - HTLV-1 Tax oncoprotein inhibits the estrogen-induced-ER alpha-Mediated BRCA1
      expression by interaction with CBP/p300 cofactors.
AB  - BRCA1 is a multifunctional tumor suppressor, whose expression is activated by the
      estrogen (E2)-liganded ERalpha receptor and regulated by certain recruited
      transcriptional co-activators. Interference with BRCA1 expression and/or
      functions leads to high risk of breast or/and ovarian cancer. Another
      multifunctional protein, HTLV-1Tax oncoprotein, is widely regarded as crucial for
      developing adult T-cell leukemia and other clinical disorders. Tax profile
      reveals that it can antagonize BRCA1 expression and/or functionality. Therefore,
      we hypothesize that Tax expression in breast cells can sensitize them to
      malignant transformation by environmental carcinogens. Here we examined Tax
      effect on BRCA1 expression by testing its influence on E2-induced expression of
      BRCA1 promoter-driven luciferase reporter (BRCA1-Luc). We found that E2 strongly
      stimulated this reporter expression by liganding to ERalpha, which consequently
      associated with BRCA1 promoter, while ERalpha concomitantly recruited CBP/p300 to
      this complex for co-operative enhancement of BRCA1 expression. Introducing Tax
      into these cells strongly blocked this E2-ERalpha-mediated activation of BRCA1
      expression. We noted, also, that Tax exerted this inhibition by binding to
      CBP/p300 without releasing them from their complex with ERalpha. Chip assay
      revealed that the binding of Tax to the CBP/p300-ERalpha complex, prevented its
      link to AP1 site. Interestingly, we noted that elevating the intracellular pool
      of CBP or p300 to excessive levels dramatically reduced the Tax-mediated
      inhibition of BRCA1 expression. Exploring the mechanism of this reduction
      revealed that the excessive co-factors were sufficient to bind separately the
      free Tax molecules, thus lowering their amount in the CBP/p300-ERalpha complex
      and relieving, thereby, the inhibition of BRCA1 expression. 

PMID- 24586744
TI  - Krill excretion boosts microbial activity in the Southern Ocean.
AB  - Antarctic krill are known to release large amounts of inorganic and organic
      nutrients to the water column. Here we test the role of krill excretion of
      dissolved products in stimulating heterotrophic bacteria on the basis of three
      experiments where ammonium and organic excretory products released by krill were
      added to bacterial assemblages, free of grazers. Our results demonstrate that the
      addition of krill excretion products (but not of ammonium alone), at levels
      expected in krill swarms, greatly stimulates bacteria resulting in an order-of
      magnitude increase in growth and production. Furthermore, they suggest that
      bacterial growth rate in the Southern Ocean is suppressed well below their
      potential by resource limitation. Enhanced bacterial activity in the presence of
      krill, which are major sources of DOC in the Southern Ocean, would further
      increase recycling processes associated with krill activity, resulting in highly
      efficient krill-bacterial recycling that should be conducive to stimulating
      periods of high primary productivity in the Southern Ocean. 

PMID- 24586745
TI  - Interferon-gamma (IFN-gamma)-mediated retinal ganglion cell death in human
      tyrosinase T cell receptor transgenic mouse.
AB  - We have recently demonstrated the characterization of human tyrosinase TCR
      bearing h3T-A2 transgenic mouse model, which exhibits spontaneous autoimmune
      vitiligo and retinal dysfunction. The purpose of current study was to determine
      the role of T cells and IFN-gamma in retina dysfunction and retinal ganglion cell
      (RGC) death using this model. RGC function was measured by pattern
      electroretinograms (ERGs) in response to contrast reversal of patterned visual
      stimuli. RGCs were visualized by fluorogold retrograde-labeling. Expression of
      CD3, IFN-gamma, GFAP, and caspases was measured by immunohistochemistry and
      Western blotting. All functional and structural changes were measured in 12-month
      old h3T-A2 mice and compared with age-matched HLA-A2 wild-type mice. Both pattern
      ERGs (42%, p = 0.03) and RGC numbers (37%, p = 0.0001) were reduced in h3T-A2
      mice when compared with wild-type mice. The level of CD3 expression was increased
      in h3T-A2 mice (h3T-A2: 174 +/- 27% vs. HLA-A2: 100%; p = 0.04). The levels of
      effector cytokine IFN-gamma were also increased significantly in h3T-A2 mice (h3T
      A2: 189 +/- 11% vs. HLA-A2: 100%; p = 0.023). Both CD3 and IFN-gamma
      immunostaining were increased in nerve fiber (NF) and RGC layers of h3T-A2 mice.
      In addition, we have seen a robust increase in GFAP staining in h3T-A2 mice
      (mainly localized to NF layer), which was substantially reduced in IFN-gamma ((-/
      )) knockout h3T-A2 mice. We also have seen an up-regulation of caspase-3 and -9
      in h3T-A2 mice. Based on our data we conclude that h3T-A2 transgenic mice exhibit
      visual defects that are mostly associated with the inner retinal layers and RGC
      function. This novel h3T-A2 transgenic mouse model provides opportunity to
      understand RGC pathology and test neuroprotective strategies to rescue RGCs.

PMID- 24586746
TI  - Comparative study of sex differences in distal femur morphology in osteoarthritic
      knees in a Chinese population.
AB  - OBJECTIVES: The purpose of this study was to investigate sex differences in
      resected distal femoral morphology in Chinese osteoarthritic knees. METHODS: The
      study included 130 osteoarthritic knees in 65 men and 65 women in China. None had
      anterior femoral osteophyte or serious patellar femoral joint degeneration. The
      following were measured using computed tomography and analyzed to identify
      morphological differences according to sex in the resected distal femurs:
      anterior lateral condylar height (ALCH), anterior medial condylar height (AMCH),
      and mediolateral (ML) and anteroposterior (AP) dimensions. The ML/AP aspect ratio
      was calculated. RESULTS: The average ALCH and AMCH were 8.2+/-1.8 mm, 3.1+/-1.5
      mm for men and 7.4+/-1.7 mm, 3.6+/-1.5 mm for women. There were significant
      differences between men and women in ALCH values (P = 0.014) but not in AMCH
      values (P = 0.09). Women had smaller ML/AP aspect ratios than men for a given AP
      dimension. This indicated that the femoral ML dimension of a prosthesis with a
      given AP dimension may have overhang in women. CONCLUSIONS: This study suggested
      that sex differences should be taken into account in the design of femoral
      prosthesis for Chinese men and women.

PMID- 24586747
TI  - A multiplex two-color real-time PCR method for quality-controlled molecular
      diagnostic testing of FFPE samples.
AB  - BACKGROUND: Reverse transcription quantitative real-time PCR (RT-qPCR) tests
      support personalized cancer treatment through more clinically meaningful
      diagnosis. However, samples obtained through standard clinical pathology
      procedures are formalin-fixed, paraffin-embedded (FFPE) and yield small samples
      with low integrity RNA containing PCR interfering substances. RT-qPCR tests able
      to assess FFPE samples with quality control and inter-laboratory reproducibility
      are needed. METHODS: We developed an RT-qPCR method by which 1) each gene was
      measured relative to a known number of its respective competitive internal
      standard molecules to control for interfering substances, 2) two-color
      fluorometric hydrolysis probes enabled analysis on a real-time platform, 3)
      external standards controlled for variation in probe fluorescence intensity, and
      4) pre-amplification maximized signal from FFPE RNA samples. Reagents were
      developed for four genes comprised by a previously reported lung cancer
      diagnostic test (LCDT) then subjected to analytical validation using synthetic
      native templates as test articles to assess linearity, signal-to-analyte
      response, lower detection threshold, imprecision and accuracy. Fitness of this
      method and these reagents for clinical testing was assessed in FFPE normal (N =
      10) and malignant (N = 10) lung samples. RESULTS: Reagents for each of four
      genes, MYC, E2F1, CDKN1A and ACTB comprised by the LCDT had acceptable linearity
      (R(2)>0.99), signal-to-analyte response (slope 1.0 +/- 0.05), lower detection
      threshold (<10 molecules) and imprecision (CV <20%). Poisson analysis confirmed
      accuracy of internal standard concentrations. Internal standards controlled for
      experimentally introduced interference, prevented false-negatives and enabled pre
      amplification to increase signal without altering measured values. In the fitness
      for purpose testing of this two-color fluorometric LCDT using surgical FFPE
      samples, the diagnostic accuracy was 93% which was similar to that previously
      reported for analysis of fresh samples. CONCLUSIONS: This quality-controlled two
      color fluorometric RT-qPCR approach will facilitate the development of reliable,
      robust RT-qPCR-based molecular diagnostic tests in FFPE clinical samples.

PMID- 24586748
TI  - A nucleolus-predominant piggyBac transposase, NP-mPB, mediates elevated
      transposition efficiency in mammalian cells.
AB  - PiggyBac is a prevalent transposon system used to deliver transgenes and
      functionally explore the mammalian untouched genomic territory. The important
      features of piggyBac transposon are the relatively low insertion site preference
      and the ability of seamless removal from genome, which allow its potential uses
      in functional genomics and regenerative medicine. Efforts to increase its
      transposition efficiency in mammals were made through engineering the
      corresponding transposase (PBase) codon usage to enhance its expression level and
      through screening for mutant PBase variants with increased enzyme activity. To
      improve the safety for its potential use in regenerative medicine applications,
      site-specific transposition was achieved by using engineered zinc finger- and
      Gal4-fused PBases. An excision-prone PBase variant has also been successfully
      developed. Here we describe the construction of a nucleolus-predominant PBase, NP
      mPB, by adding a nucleolus-predominant (NP) signal peptide from HIV-1 TAT protein
      to a mammalian codon-optimized PBase (mPB). Although there is a predominant
      fraction of the NP-mPB-tGFP fusion proteins concentrated in the nucleoli, an
      insertion site preference toward nucleolar organizer regions is not detected.
      Instead a 3-4 fold increase in piggyBac transposition efficiency is reproducibly
      observed in mouse and human cells. 

PMID- 24586750
TI  - The association between smoking and ectopic pregnancy: why nicotine is BAD for
      your fallopian tube.
AB  - Epidemiological studies have shown that cigarette smoking is a major risk factor
      for tubal ectopic pregnancy but the reason for this remains unclear. Here, we set
      out to determine the effect of smoking on Fallopian tube gene expression. An
      oviductal epithelial cell line (OE-E6/E7) and explants of human Fallopian tubes
      from non-pregnant women (n = 6) were exposed to physiologically relevant
      concentrations of cotinine, the principle metabolite of nicotine, and changes in
      gene expression analyzed using the Illumina Human HT-12 array. Cotinine sensitive
      genes identified through this process were then localized and quantified in
      Fallopian tube biopsies from non-pregnant smokers (n = 10) and non-smokers (n =
      11) using immunohistochemistry and TaqMan RT-PCR. The principle cotinine induced
      change in gene expression detected by the array analysis in both explants and the
      cell line was significant down regulation (P<0.05) of the pro-apoptotic gene BAD.
      We therefore assessed the effect of smoking on cell turnover in retrospectively
      collected human samples. Consistent with the array data, smoking was associated
      with decreased levels of BAD transcript (P<0.01) and increased levels of BCL2
      transcript (P<0.05) in Fallopian tube biopsies. BAD and BCL2 specific
      immunolabelling was localized to Fallopian tube epithelium. Although no other
      significant differences in levels of apoptosis or cell cycle associated proteins
      were observed, smoking was associated with significant changes in the morphology
      of the Fallopian tube epithelium (P<0.05). These results suggest that smoking may
      alter tubal epithelial cell turnover and is associated with structural, as well
      as functional, changes that may contribute to the development of ectopic
      pregnancy.

PMID- 24586751
TI  - Traumatic severity and trait resilience as predictors of posttraumatic stress
      disorder and depressive symptoms among adolescent survivors of the Wenchuan
      earthquake.
AB  - PURPOSE: To examine the associations between trauma severity, trait resilience,
      and posttraumatic stress disorder (PTSD) and depressive symptoms among adolescent
      survivors of the Wenchuan earthquake, China. METHODS: 788 participants were
      randomly selected from secondary schools in the counties of Wenchuan and Maoxian,
      the two areas most severely affected by the earthquake. Participants completed
      four main questionnaires including the Child PTSD Symptom Scale, the Center for
      Epidemiologic Studies Depression Scale for Children, the Connor and Davidson's
      Resilience Scale, and the Severity of Exposure to Earthquake Scale. RESULTS:
      After adjusting for the effect of age and gender, four aspects of trauma severity
      (i.e., direct exposure, indirect exposure, worry about others, and house damage)
      were positively associated with the severity of PTSD and depressive symptoms,
      whereas trait resilience was negatively associated with PTSD and depressive
      symptoms and moderated the relationship between subjective experience (i.e.,
      worry about others) and PTSD and depressive symptoms. CONCLUSIONS: Several
      aspects (i.e., direct exposure, indirect exposure, worry about others, and house
      damage) of earthquake experiences may be important risk factors for the
      development and maintenance of PTSD and depression. Additionally, trait
      resilience exhibits the beneficial impact on PTSD and depressive symptoms and
      buffers the effect of subjective experience (i.e., worry about others) on PTSD
      and depressive symptoms.

PMID- 24586749
TI  - Mice carrying a hypomorphic Evi1 allele are embryonic viable but exhibit severe
      congenital heart defects.
AB  - The ecotropic viral integration site 1 (Evi1) oncogenic transcription factor is
      one of a number of alternative transcripts encoded by the Mds1 and Evi1 complex
      locus (Mecom). Overexpression of Evi1 has been observed in a number of myeloid
      disorders and is associated with poor patient survival. It is also amplified
      and/or overexpressed in many epithelial cancers including nasopharyngeal
      carcinoma, ovarian carcinoma, ependymomas, and lung and colorectal cancers. Two
      murine knockout models have also demonstrated Evi1's critical role in the
      maintenance of hematopoietic stem cell renewal with its absence resulting in the
      death of mutant embryos due to hematopoietic failure. Here we characterize a
      novel mouse model (designated Evi1(fl3)) in which Evi1 exon 3, which carries the
      ATG start, is flanked by loxP sites. Unexpectedly, we found that germline
      deletion of exon3 produces a hypomorphic allele due to the use of an alternative
      ATG start site located in exon 4, resulting in a minor Evi1 N-terminal truncation
      and a block in expression of the Mds1-Evi1 fusion transcript.
      Evi1(deltaex3/deltaex3) mutant embryos showed only a mild non-lethal
      hematopoietic phenotype and bone marrow failure was only observed in adult Vav
      iCre/+, Evi1(fl3/fl3) mice in which exon 3 was specifically deleted in the
      hematopoietic system. Evi1(deltaex3/deltaex3) knockout pups are born in normal
      numbers but die during the perinatal period from congenital heart defects.
      Database searches identified 143 genes with similar mutant heart phenotypes as
      those observed in Evi1(deltaex3/deltaex3) mutant pups. Interestingly, 42 of these
      congenital heart defect genes contain known Evi1-binding sites, and expression of
      18 of these genes are also effected by Evi1 siRNA knockdown. These results show a
      potential functional involvement of Evi1 target genes in heart development and
      indicate that Evi1 is part of a transcriptional program that regulates cardiac
      development in addition to the development of blood. 

PMID- 24586753
TI  - African elephant alarm calls distinguish between threats from humans and bees.
AB  - The Samburu pastoralists of Northern Kenya co-exist with African elephants,
      Loxodonta africana, and compete over resources such as watering holes. Audio
      playback experiments demonstrate that African elephants produce alarm calls in
      response to the voices of Samburu tribesmen. When exposed to adult male Samburu
      voices, listening elephants exhibited vigilance behavior, flight behavior, and
      produced vocalizations (rumbles, roars and trumpets). Rumble vocalizations were
      most common and were characterized by increased and more variable fundamental
      frequencies, and an upward shift in the first [F1] and second [F2] formant
      locations, compared to control rumbles. When exposed to a sequence of these
      recorded rumbles, roars and trumpets, listening elephants also exhibited
      vigilance and flight behavior. The same behavior was observed, in lesser degrees,
      both when the roars and trumpets were removed, and when the second formants were
      artificially lowered to levels typical of control rumbles. The "Samburu alarm
      rumble" is acoustically distinct from the previously described "bee alarm
      rumble." The bee alarm rumbles exhibited increased F2, while Samburu alarm
      rumbles exhibited increased F1 and F2, compared to controls. Moreover, the
      behavioral reactions to the two threats were different. Elephants exhibited
      vigilance and flight behavior in response to Samburu and bee stimuli and to both
      alarm calls, but headshaking behavior only occurred in response to bee sounds and
      bee alarm calls. In general, increasingly threatening stimuli elicited alarm
      calls with increases in F0 and in formant locations, and increasing numbers of
      these acoustic cues in vocal stimuli elicited increased vigilance and flight
      behavior in listening elephants. These results show that African elephant alarm
      calls differentiate between two types of threat and reflect the level of urgency
      of threats.

PMID- 24586752
TI  - Pseudomonas-derived ceramidase induces production of inflammatory mediators from
      human keratinocytes via sphingosine-1-phosphate.
AB  - Ceramide is important for water retention and permeability barrier functions in
      the stratum corneum, and plays a key role in the pathogenesis of atopic
      dermatitis (AD). A Pseudomonas aeruginosa-derived neutral ceramidase (PaCDase)
      isolated from a patient with AD was shown to effectively degrade ceramide in the
      presence of Staphylococcus aureus-derived lipids or neutral detergents. However,
      the effect of ceramide metabolites on the functions of differentiating
      keratinocytes is poorly understood. We found that the ceramide metabolite
      sphingosine-1-phosphate (S1P) stimulated the production of inflammatory mediators
      such as TNF-alpha and IL-8 from three-dimensionally cultured human primary
      keratinocytes (termed "3D keratinocytes"), which form a stratum corneum. PaCDase
      alone did not affect TNF-alpha gene expression in 3D keratinocytes. In the
      presence of the detergent Triton X-100, which damages stratum corneum structure,
      PaCDase, but not heat-inactivated PaCDase or PaCDase-inactive mutant, induced the
      production of TNF-alpha, endothelin-1, and IL-8, indicating that this production
      was dependent on ceramidase activity. Among various ceramide metabolites,
      sphingosine and S1P enhanced the gene expression of TNF-alpha, endothelin-1, and
      IL-8. The PaCDase-enhanced expression of these genes was inhibited by a
      sphingosine kinase inhibitor and by an S1P receptor antagonist VPC 23019. The TNF
      alpha-binding antibody infliximab suppressed the PaCDase-induced upregulation of
      IL-8, but not TNF-alpha, mRNA. PaCDase induced NF-kappaB p65 phosphorylation. The
      NF-kappaB inhibitor curcumin significantly inhibited PaCDase-induced expression
      of IL-8 and endothelin-1. VPC 23019 and infliximab inhibited PaCDase-induced NF
      kappaB p65 phosphorylation and reduction in the protein level of the NF-kappaB
      inhibitor IkappaBalpha. Collectively, these findings suggest that (i) 3D
      keratinocytes produce S1P from sphingosine, which is produced through the
      hydrolysis of ceramide by PaCDase, (ii) S1P induces the production of TNF-alpha
      via S1P receptors, and (iii) released TNF-alpha stimulates the production of
      inflammatory mediators such as IL-8. 

PMID- 24586754
TI  - JAK2-centered interactome hotspot identified by an integrative network algorithm
      in acute Stanford type A aortic dissection.
AB  - The precise mechanisms underlying dissections, especially those without
      connective tissue diseases or congenital vascular diseases, are incompletely
      understood. This study attempted to identify both the expression profile of the
      dissected ascending aorta and the interactome hotspots associated with the
      disease, using microarray technology and gene regulatory network analysis. There
      were 2,737 genes differentially expressed between patients with acute Stanford
      type A aortic dissection and controls. Eight interactome hotspots significantly
      associated with aortic dissection were identified by an integrative network
      algorithm. In particular, we identified a JAK2-centered expression module, which
      was validated in an independent gene expression microarray data set, and which
      was characterized by over-expressed cytokines and receptors in acute aortic
      dissection cases, indicating that JAK2 may play a key role in the inflammatory
      process, which potentially contributes to the occurrence of acute aortic
      dissection. Overall, the analytical strategy used in this study offered the
      possibility to identify functional relevant network modules and subsequently
      facilitated the biological interpretation in the complicated disease. 

PMID- 24586755
TI  - Multicenter external quality assessment program for PCR detection of
      Mycobacterium ulcerans in clinical and environmental specimens.
AB  - BACKGROUND: Mycobacterium ulcerans is the causative agent of Buruli ulcer (BU), a
      necrotizing disease of the skin, soft tissue and bone. PCR is increasingly used
      in the diagnosis of BU and in research on the mode of transmission and
      environmental reservoir of M. ulcerans. METHODOLOGY/PRINCIPAL FINDINGS: The aim
      of this study was to evaluate the performance of laboratories in detecting M.
      ulcerans using molecular tests in clinical and environmental samples by
      implementing sequential multicenter external quality assessment (EQA) programs.
      The second round of the clinical EQA program revealed somewhat improved
      performance. CONCLUSIONS/SIGNIFICANCE: Ongoing EQA programs remain essential and
      continued participation in future EQA programs by laboratories involved in the
      molecular testing of clinical and environmental samples for M. ulcerans for
      diagnostic and research purposes is strongly encouraged. Broad participation in
      such EQA programs also benefits the harmonization of quality in the BU research
      community and enhances the credibility of advances made in solving the
      transmission enigma of M. ulcerans.

PMID- 24586756
TI  - Suicidal behaviors among adolescents in juvenile detention: role of adverse life
      experiences.
AB  - PURPOSE: The purpose of this study was to assess the influence of multiple
      adverse life experiences (sexual abuse, homelessness, running away, and substance
      abuse in the family) on suicide ideation and suicide attempt among adolescents at
      an urban juvenile detention facility in the United States. MATERIALS AND METHODS:
      The study sample included a total of 3,156 adolescents processed at a juvenile
      detention facility in an urban area in Ohio between 2003 and 2007. The
      participants, interacting anonymously with a voice enabled computer, self
      administered a questionnaire with 100 items related to health risk behaviors.
      RESULTS: Overall 19.0% reported ever having thought about suicide (suicide
      ideation) and 11.9% reported ever having attempted suicide (suicide attempt). In
      the multivariable logistic regression analysis those reporting sexual abuse (Odds
      Ratio = 2.75; 95% confidence interval  = 2.08-3.63) and homelessness (1.51; 1.17
      1.94) were associated with increased odds of suicide ideation, while sexual abuse
      (3.01; 2.22-4.08), homelessness (1.49; 1.12-1.98), and running away from home
      (1.38; 1.06-1.81) were associated with increased odds of a suicide attempt. Those
      experiencing all four adverse events were 7.81 times more likely (2.41-25.37) to
      report having ever attempted suicide than those who experienced none of the
      adverse events. CONCLUSIONS: Considering the high prevalence of adverse life
      experiences and their association with suicidal behaviors in detained
      adolescents, these factors should not only be included in the suicide screening
      tools at the intake and during detention, but should also be used for the
      intervention programming for suicide prevention.

PMID- 24586757
TI  - Oocytes with a dark zona pellucida demonstrate lower fertilization, implantation
      and clinical pregnancy rates in IVF/ICSI cycles.
AB  - The morphological assessment of oocytes is important for embryologists to
      identify and select MII oocytes in IVF/ICSI cycles. Dysmorphism of oocytes
      decreases viability and the developmental potential of oocytes as well as the
      clinical pregnancy rate. Several reports have suggested that oocytes with a dark
      zona pellucida (DZP) correlate with the outcome of IVF treatment. However, the
      effect of DZP on oocyte quality, fertilization, implantation, and pregnancy
      outcome were not investigated in detail. In this study, a retrospective analysis
      was performed in 268 infertile patients with fallopian tube obstruction and/or
      male factor infertility. In 204 of these patients, all oocytes were surrounded by
      a normal zona pellucida (NZP, control group), whereas 46 patients were found to
      have part of their retrieved oocytes enclosed by NZP and the other by DZP (Group
      A). In addition, all oocytes enclosed by DZP were retrieved from 18 patients
      (Group B). No differences were detected between the control and group A. Compared
      to the control group, the rates of fertilization, good quality embryos,
      implantation and clinical pregnancy were significantly decreased in group B.
      Furthermore, mitochondria in oocytes with a DZP in both of the two study groups
      (A and B) were severely damaged with several ultrastructural alterations, which
      were associated with an increased density of the zona pellucida and
      vacuolization. Briefly, oocytes with a DZP affected the clinical outcome in
      IVF/ICSI cycles and appeared to contain more ultrastructural alterations. Thus,
      DZP could be used as a potential selective marker for embryologists during daily
      laboratory work. 

PMID- 24586758
TI  - Progression of brain atrophy in spinocerebellar ataxia type 2: a longitudinal
      tensor-based morphometry study.
AB  - Spinocerebellar ataxia type 2 (SCA2) is the second most frequent autosomal
      dominant inherited ataxia worldwide. We investigated the capability of magnetic
      resonance imaging (MRI) to track in vivo progression of brain atrophy in SCA2 by
      examining twice 10 SCA2 patients (mean interval 3.6 years) and 16 age- and gender
      matched healthy controls (mean interval 3.3 years) on the same 1.5 T MRI scanner.
      We used T1-weighted images and tensor-based morphometry (TBM) to investigate
      volume changes and the Inherited Ataxia Clinical Rating Scale to assess the
      clinical deficit. With respect to controls, SCA2 patients showed significant
      higher atrophy rates in the midbrain, including substantia nigra, basis pontis,
      middle cerebellar peduncles and posterior medulla corresponding to the gracilis
      and cuneatus tracts and nuclei, cerebellar white matter (WM) and cortical gray
      matter (GM) in the inferior portions of the cerebellar hemisphers. No differences
      in WM or GM volume loss were observed in the supratentorial compartment. TBM
      findings did not correlate with modifications of the neurological deficit. In
      conclusion, MRI volumetry using TBM is capable of demonstrating the progression
      of pontocerebellar atrophy in SCA2, supporting a possible role of MRI as
      biomarker in future trials. 

PMID- 24586759
TI  - Protein malnutrition impairs the immune response and influences the severity of
      infection in a hamster model of chronic visceral leishmaniasis.
AB  - Leishmaniasis remains one of the world's most devastating neglected tropical
      diseases. It mainly affects developing countries, where it often co-exists with
      chronic malnutrition, one of the main risk factors for developing the disease.
      Few studies have been published, however, on the relationship between
      leishmaniasis progression and malnutrition. The present paper reports the
      influence of protein malnutrition on the immune response and visceral disease
      development in adult hamsters infected with Leishmania infantum fed either
      standard or low protein diets. The low protein diet induced severe malnutrition
      in these animals, and upon infection with L. infantum 33% had severe visceral
      leishmaniasis compared to only 8% of animals fed the standard diet. The infected,
      malnourished animals showed notable leukocyte depletion, mild specific antibody
      responses, impairment of lymphoproliferation, presence of parasites in blood
      (16.67% of the hamsters) and significant increase of the splenic parasite burden.
      Animals fed standard diet suffered agranulocytosis and monocytopenia, but showed
      stronger specific immune responses and had lower parasite loads than their
      malnourished counterparts. The present results show that protein malnutrition
      promotes visceral leishmaniasis and provide clues regarding the mechanisms
      underlying the impairment of the immune system. 

PMID- 24586760
TI  - Effect of immunoglobin-like transcript 7 cross-linking on plasmacytoid dendritic
      cells differentiation into antigen-presenting cells.
AB  - Plasmacytoid dendritic cells (pDC) are innate immunity effector cells which play
      a critical role in the transition from innate to adaptive immune response.
      Circulating blood pDC present an immature phenotype and can differentiate into
      either antigen-presenting cells (APC) or type I interferon (IFN-I)-producing
      cells (IPC). The immunoglobulin-like transcript (ILT)7 is a surface receptor
      expressed by immature pDC, and ILT7 cross-linking (XL-ILT7) inhibits IFN-I
      production by pDC in response to toll-like receptor (TLR)7 and 9 stimulation. We
      used peripheral blood mononuclear cells (PBMC) from healthy donors to test the
      effect of XL-ILT7 on 1) TLR7/9-mediated regulation of gut mucosal (alpha4beta7
      integrin) and lymph node (CCR7) migration markers; and 2) the maturation of pDC
      into APC. We found that XL-ILT7 mitigated the upregulation of CCR7 and enhanced
      that of beta7 on TLR7/9-stimulated pDC. TLR7/9 stimulation induced upregulation
      of CD40, CD80 and CD86. CD40 expression was partially reduced by XL-ILT7, whereas
      CD86 was further enhanced. Plasmacytoid DC stimulated with TLR9 ligand in
      presence of XL-ILT7 retained the ability to induce T cell proliferation and
      activation in response to staphylococcal enterotoxin B (SEB) in pDC-T cell co
      cultures. Our results suggest that XL-ILT7 favours the differentiation of
      immature pDC into APC rather than IPC. 

PMID- 24586761
TI  - Conducting polymer electrodes for gel electrophoresis.
AB  - In nearly all cases, electrophoresis in gels is driven via the electrolysis of
      water at the electrodes, where the process consumes water and produces
      electrochemical by-products. We have previously demonstrated that pi-conjugated
      polymers such as poly(3,4-ethylenedioxythiophene) (PEDOT) can be placed between
      traditional metal electrodes and an electrolyte to mitigate electrolysis in
      liquid (capillary electroosmosis/electrophoresis) systems. In this report, we
      extend our previous result to gel electrophoresis, and show that electrodes
      containing PEDOT can be used with a commercial polyacrylamide gel electrophoresis
      system with minimal impact to the resulting gel image or the ionic transport
      measured during a separation. 

PMID- 24586762
TI  - Effects of beta-lactam antibiotics and fluoroquinolones on human gut microbiota
      in relation to Clostridium difficile associated diarrhea.
AB  - Clostridium difficile infections are an emerging health problem in the modern
      hospital environment. Severe alterations of the gut microbiome with loss of
      resistance to colonization against C. difficile are thought to be the major
      trigger, but there is no clear concept of how C. difficile infection evolves and
      which microbiological factors are involved. We sequenced 16S rRNA amplicons
      generated from DNA and RNA/cDNA of fecal samples from three groups of individuals
      by FLX technology: (i) healthy controls (no antibiotic therapy); (ii) individuals
      receiving antibiotic therapy (Ampicillin/Sulbactam, cephalosporins, and
      fluoroquinolones with subsequent development of C. difficile infection or (iii)
      individuals receiving antibiotic therapy without C. difficile infection. We
      compared the effects of the three different antibiotic classes on the intestinal
      microbiome and the effects of alterations of the gut microbiome on C. difficile
      infection at the DNA (total microbiota) and rRNA (potentially active) levels. A
      comparison of antibiotic classes showed significant differences at DNA level, but
      not at RNA level. Among individuals that developed or did not develop a C.
      difficile infection under antibiotics we found no significant differences. We
      identified single species that were up- or down regulated in individuals
      receiving antibiotics who developed the infection compared to non-infected
      individuals. We found no significant differences in the global composition of the
      transcriptionally active gut microbiome associated with C. difficile infections.
      We suggest that up- and down regulation of specific bacterial species may be
      involved in colonization resistance against C. difficile providing a potential
      therapeutic approach through specific manipulation of the intestinal microbiome. 

PMID- 24586763
TI  - Addressing the challenge of assessing physician-level screening performance:
      mammography as an example.
AB  - BACKGROUND: Motivated by the challenges in assessing physician-level cancer
      screening performance and the negative impact of misclassification, we propose a
      method (using mammography as an example) that enables confident assertion of
      adequate or inadequate performance or alternatively recognizes when more data is
      required. METHODS: Using established metrics for mammography screening
      performance-cancer detection rate (CDR) and recall rate (RR)-and observed
      benchmarks from the Breast Cancer Surveillance Consortium (BCSC), we calculate
      the minimum volume required to be 95% confident that a physician is performing at
      or above benchmark thresholds. We graphically display the minimum observed CDR
      and RR values required to confidently assert adequate performance over a range of
      interpretive volumes. We use a prospectively collected database of consecutive
      mammograms from a clinical screening program outside the BCSC to illustrate how
      this method classifies individual physician performance as volume accrues.
      RESULTS: Our analysis reveals that an annual interpretive volume of 2770
      screening mammograms, above the United States' (US) mandatory (480) and average
      (1777) annual volumes but below England's mandatory (5000) annual volume is
      necessary to confidently assert that a physician performed adequately. In our
      analyzed US practice, a single year of data uniformly allowed confident assertion
      of adequate performance in terms of RR but not CDR, which required aggregation of
      data across more than one year. CONCLUSION: For individual physician quality
      assessment in cancer screening programs that target low incidence populations,
      considering imprecision in observed performance metrics due to small numbers of
      patients with cancer is important.

PMID- 24586765
TI  - Improved lanthipeptide detection and prediction for antiSMASH.
AB  - Lanthipeptides are a class of ribosomally synthesised and post-translationally
      modified peptide (RiPP) natural products from the bacterial secondary metabolism.
      Their name is derived from the characteristic lanthionine or methyl-lanthionine
      residues contained in the processed peptide. Lanthipeptides that possess an
      antibacterial activity are called lantibiotics. Whereas multiple tools exist to
      identify lanthipeptide gene clusters from genomic data, no programs are available
      to predict the post-translational modifications of lanthipeptides, such as the
      proteolytic cleavage of the leader peptide part or tailoring modifications based
      on the analysis of the gene cluster sequence. antiSMASH is a software pipeline
      for the identification of secondary metabolite biosynthetic clusters from genomic
      input and the prediction of products produced by the identified clusters. Here we
      present a novel antiSMASH module using a rule-based approach to combine signature
      motifs for biosynthetic enzymes and lanthipeptide-specific cleavage site motifs
      to identify lanthipeptide clusters in genomic data, assign the specific
      lanthipeptide class, predict prepeptide cleavage, tailoring reactions, and the
      processed molecular weight of the mature peptide products. 

PMID- 24586764
TI  - Placental pathology, perinatal death, neonatal outcome, and neurological
      development: a systematic review.
AB  - BACKGROUND: The placenta plays a crucial role during pregnancy for growth and
      development of the fetus. Less than optimal placental performance may result in
      morbidity or even mortality of both mother and fetus. Awareness among
      pediatricians, however, of the benefit of placental findings for neonatal care,
      is limited. OBJECTIVES: To provide a systematic overview of the relation between
      placental lesions and neonatal outcome. DATA SOURCES: Pubmed database, reference
      lists of selected publications and important research groups in the field. STUDY
      APPRAISAL AND SYNTHESIS METHODS: We systematically searched the Pubmed database
      for literature on the relation between placental lesions and fetal and neonatal
      mortality, neonatal morbidity and neurological outcome. We conducted three
      separate searches starting with a search for placental pathology and fetal and
      neonatal mortality, followed by placental pathology and neonatal morbidity, and
      finally placental pathology and neurological development. We limited our search
      to full-text articles published in English from January 1995 to October 2013. We
      refined our search results by selecting the appropriate articles from the ones
      found during the initial searches. The first selection was based on the title,
      the second on the abstract, and the third on the full article. The quality of the
      selected articles was determined by using the Newcastle-Ottawa Quality Assessment
      Scale. RESULTS: Placental lesions are one of the main causes of fetal death,
      where placental lesions consistent with maternal vascular underperfusion are most
      important. Several neonatal problems are also associated with placental lesions,
      whereby ascending intrauterine infection (with a fetal component) and fetal
      thrombotic vasculopathy constitute the greatest problem. CONCLUSIONS: The
      placenta plays a key role in fetal and neonatal mortality, morbidity, and
      outcome. Pediatricians should make an effort to obtain the results of placental
      examinations.

PMID- 24586766
TI  - Regulation of 11beta-hydroxysteroid dehydrogenase type 1 and 7alpha-hydroxylase
      CYP7B1 during social stress.
AB  - 11beta-hydroxysteroid dehydrogenase type 1 (11HSD1) is an enzyme that amplifies
      intracellular glucocorticoid concentration by the conversion of inert
      glucocorticoids to active forms and is involved in the interconversion of 7-oxo-
      and 7-hydroxy-steroids, which can interfere with the activation of
      glucocorticoids. The presence of 11HSD1 in the structures of the hypothalamic
      pituitary-adrenal (HPA) axis suggests that this enzyme might play a role in the
      regulation of HPA output. Here we show that the exposure of Fisher 344 rats to
      mild social stress based on the resident-intruder paradigm increased the
      expression of 11HSD1 and CYP7B1, an enzyme that catalyzes 7-hydroxylation of
      steroids. We found that social behavioral profile of intruders was significantly
      decreased whereas their plasma levels of corticosterone were increased more than
      in residents. The stress did not modulate 11HSD1 in the HPA axis (paraventricular
      nucleus, pituitary, adrenal cortex) but selectively upregulated 11HSD1 in some
      regions of the hippocampus, amygdala and prelimbic cortex. In contrast, CYP7B1
      was upregulated not only in the hippocampus and amygdala but also in
      paraventricular nucleus and pituitary. Furthermore, the stress downregulated
      11HSD1 in the thymus and upregulated it in the spleen and mesenteric lymphatic
      nodes whereas CYP7B1 was upregulated in all of these lymphoid organs. The
      response of 11HSD1 to stress was more obvious in intruders than in residents and
      the response of CYP7B1 to stress predominated in residents. We conclude that
      social stress induces changes in enzymes of local metabolism of glucocorticoids
      in lymphoid organs and in brain structures associated with the regulation of the
      HPA axis. In addition, the presented data clearly suggest a role of 11HSD1 in
      modulation of glucocorticoid feedback of the HPA axis during stress. 

PMID- 24586767
TI  - RAGE controls activation and anti-inflammatory signalling of protein C.
AB  - AIMS: The receptor for advanced glycation endproducts, RAGE, is a multiligand
      receptor and NF-kappaB activator leading to perpetuation of inflammation. We
      investigated whether and how RAGE is involved in mediation of anti-inflammatory
      properties of protein C. METHODS AND RESULTS: We analyzed the effect of protein C
      on leukocyte adhesion and transmigration in WT- and RAGE-deficient mice using
      intravital microscopy of cremaster muscle venules during trauma- and TNFalpha
      induced inflammation. Both, protein C (PC, Ceprotin, 100 U/kg) and activated
      protein C (aPC, 24 ug/kg/h) treatment significantly inhibited leukocyte adhesion
      in WT mice in these inflammation models. The impaired leukocyte adhesion after
      trauma-induced inflammation in RAGE knockout mice could not be further reduced by
      PC and aPC. After TNFalpha-stimulation, however, aPC but not PC treatment
      effectively blocked leukocyte adhesion in these mice. Consequently, we asked
      whether RAGE is involved in PC activation. Since RAGE-deficient mice and
      endothelial cells showed insufficient PC activation, and since thrombomodulin
      (TM) and endothelial protein C receptor (EPCR) are reduced on the mRNA and
      protein level in RAGE deficient endothelial cells, an involvement of RAGE in TM
      EPCR-dependent PC activation is likely. Moreover, TNFalpha-induced activation of
      MAPK and upregulation of ICAM-1 and VCAM-1 are reduced both in response to aPC
      treatment and in the absence of RAGE. Thus, there seems to be interplay of the
      RAGE and the PC pathway in inflammation. CONCLUSION: RAGE controls anti
      inflammatory properties and activation of PC, which might involve EPCR and TM.

PMID- 24586768
TI  - Oligodendroglial p130Cas is a target of Fyn kinase involved in process formation,
      cell migration and survival.
AB  - Oligodendrocytes are the myelinating glial cells of the central nervous system.
      In the course of brain development, oligodendrocyte precursor cells migrate, scan
      the environment and differentiate into mature oligodendrocytes with multiple
      cellular processes which recognize and ensheath neuronal axons. During
      differentiation, oligodendrocytes undergo dramatic morphological changes
      requiring cytoskeletal rearrangements which need to be tightly regulated. The non
      receptor tyrosine kinase Fyn plays a central role in oligodendrocyte
      differentiation and myelination. In order to improve our understanding of the
      role of oligodendroglial Fyn kinase, we have identified Fyn targets in these
      cells. Purification and mass-spectrometric analysis of tyrosine-phosphorylated
      proteins in response to overexpressed active Fyn in the oligodendrocyte precursor
      cell line Oli-neu, yielded the adaptor molecule p130Cas. We analyzed the function
      of this Fyn target in oligodendroglial cells and observed that reduction of
      p130Cas levels by siRNA affects process outgrowth, the thickness of cellular
      processes and migration behavior of Oli-neu cells. Furthermore, long term p130Cas
      reduction results in decreased cell numbers as a result of increased apoptosis in
      cultured primary oligodendrocytes. Our data contribute to understanding the
      molecular events taking place during oligodendrocyte migration and morphological
      differentiation and have implications for myelin formation. 

PMID- 24586769
TI  - Disulfide linkages in Plasmodium falciparum plasmepsin-i are essential elements
      for its processing activity and multi-milligram recombinant production yield.
AB  - Plasmodium falciparum plasmepsin-I (PM-I) has been considered a potential drug
      target for the parasite that causes fatal malaria in human. Determination of PM-I
      structures for rational design of its inhibitors is hindered by the difficulty in
      obtaining large quantity of soluble enzyme. Nearly all attempts for its
      heterologous expression in Escherichia coli result in the production of insoluble
      proteins in both semi-pro-PM-I and its truncated form, and thus require protein
      refolding. Moreover, the yields of purified, soluble PM-I from all reported
      studies are very limited. Exclusion of truncated semi-pro-PM-I expression in E.
      coli C41(DE3) is herein reported. We also show that the low preparation yield of
      purified semi-pro-PM-I with autoprocessing ability is mainly a result of
      structural instability of the refolded enzyme in acidic conditions due to
      incomplete formation of disulfide linkages. Upon formation of at least one of the
      two natural disulfide bonds, nearly all of the refolded semi-pro-PM-I could be
      activated to its mature form. A significantly improved yield of 10 mg of semi-pro
      PM-I per liter of culture, which resulted in 6-8 mg of the mature PM-I, was
      routinely obtained using this strategy. 

PMID- 24586770
TI  - Subcortical correlates of individual differences in aptitude.
AB  - The study of individual differences encompasses broad constructs including
      intelligence, creativity, and personality. However, substantially less research
      is devoted to the study of specific aptitudes in spite of their importance to
      educational, occupational, and avocational success. We sought to determine
      subcortical brain structural correlates of several broad aptitudes including
      Math, Vocabulary, Foresight, Paper Folding, and Inductive Reasoning in a large (N
      = 107), healthy, young (age range  = 16-29) cohort. Subcortical volumes were
      measured using an automated technique (FreeSurfer) across structures including
      bilateral caudate, putamen, globus pallidus, thalamus, nucleus accumbens,
      hippocampus, amygdala, and five equal regions of the corpus callosum. We found
      that performance on measures of each aptitude was predicted by different
      subcortical structures: Math--higher right nucleus accumbens volume; Vocabulary-
      higher left hippocampus volume; Paper Folding--higher right thalamus volume;
      Foresight--lower right thalamus and higher mid anterior corpus callosum volume;
      Inductive Reasoning--higher mid anterior corpus callosum volume. Our results
      support general findings, within the cognitive neurosciences, showing
      lateralization of structure-function relationships, as well as more specific
      relationships between individual structures (e.g., left hippocampus) and
      functions relevant to particular aptitudes (e.g., Vocabulary).

PMID- 24586771
TI  - Small-cell lung cancer in England: trends in survival and chemotherapy using the
      National Lung Cancer Audit.
AB  - BACKGROUND: The purpose of this study was to identify trends in survival and
      chemotherapy use for individuals with small-cell lung cancer (SCLC) in England
      using the National Lung Cancer Audit (NLCA). METHODS: We used data from the NLCA
      database to identify people with histologically proven SCLC from 2004-2011. We
      calculated the median survival by stage and assessed whether patient
      characteristics changed over time. We also assessed whether the proportion of
      patients with records of chemotherapy and/or radiotherapy changed over time.
      RESULTS: 18,513 patients were diagnosed with SCLC in our cohort. The median
      survival was 6 months for all patients, 1 year for those with limited stage and 4
      months for extensive stage. 69% received chemotherapy and this proportion changed
      very slightly over time (test for trends p = 0.055). Age and performance status
      of patients remained stable over the study period, but the proportion of patients
      staged increased (p-value<0.001), mainly because of improved data completeness.
      There has been an increase in the proportion of patients that had a record of
      receiving both chemotherapy and radiotherapy each year (from 19% to 40% in
      limited and from 9% to 21% in extensive stage from 2004 to 2011). Patients who
      received chemotherapy with radiotherapy had better survival compared with any
      other treatment (HR 0.24, 95% CI 0.23-0.25). CONCLUSION: Since 2004, when the
      NLCA was established, the proportion of patients with SCLC having chemotherapy
      has remained static. We have found an upward trend in the proportion of patients
      receiving both chemotherapy and radiotherapy which corresponded to a better
      survival in this group, but as it only applied for a small proportion of
      patients, it was not enough to change the overall survival.

PMID- 24586772
TI  - Increased prolactin levels are associated with impaired processing speed in
      subjects with early psychosis.
AB  - Hyperprolactinaemia, a common side effect of some antipsychotic drugs, is also
      present in drug-naive psychotic patients and subjects at risk for psychosis.
      Recent studies in non-psychiatric populations suggest that increased prolactin
      may have negative effects on cognition. The aim of our study was to explore
      whether high plasma prolactin levels are associated with poorer cognitive
      functioning in subjects with early psychoses. We studied 107 participants: 29
      healthy subjects and 78 subjects with an early psychosis (55 psychotic disorders
      with <3 years of illness, 23 high-risk subjects). Cognitive assessment was
      performed with the MATRICS Cognitive Consensus Cognitive Battery, and prolactin
      levels were determined as well as total cortisol levels in plasma.
      Psychopathological status was assessed and the use of psychopharmacological
      treatments (antipsychotics, antidepressants, benzodiazepines) recorded. Prolactin
      levels were negatively associated with cognitive performance in processing speed,
      in patients with a psychotic disorder and high-risk subjects. In the latter
      group, increased prolactin levels were also associated with impaired reasoning
      and problem solving and poorer general cognition. In a multiple linear regression
      analysis conducted in both high-risk and psychotic patients, controlling for
      potential confounders, prolactin and benzodiazepines were independently related
      to poorer cognitive performance in the speed of processing domain. A mediation
      analysis showed that both prolactin and benzodiazepine treatment act as mediators
      of the relationship between risperidone/paliperidone treatment and speed of
      processing. These results suggest that increased prolactin levels are associated
      with impaired processing speed in early psychosis. If these results are confirmed
      in future studies, strategies targeting reduction of prolactin levels may improve
      cognition in this population. 

PMID- 24586773
TI  - The 2-pore domain potassium channel TREK-1 regulates stretch-induced detachment
      of alveolar epithelial cells.
AB  - Acute Respiratory Distress Syndrome remains challenging partially because the
      underlying mechanisms are poorly understood. While inflammation and loss of
      barrier function are associated with disease progression, our understanding of
      the biophysical mechanisms associated with ventilator-associated lung injury is
      incomplete. In this line of thinking, we recently showed that changes in the F
      actin content and deformability of AECs lead to cell detachment with mechanical
      stretch. Elsewhere, we discovered that cytokine secretion and proliferation were
      regulated in part by the stretch-activated 2-pore domain K(+) (K2P) channel TREK
      1 in alveolar epithelial cells (AECs). As such, the aim of the current study was
      to determine whether TREK-1 regulated the mechanobiology of AECs through
      cytoskeletal remodeling and cell detachment. Using a TREK-1-deficient human AEC
      line (A549), we examined the cytoskeleton by confocal microscopy and quantified
      differences in the F-actin content. We used nano-indentation with an atomic force
      microscope to measure the deformability of cells and detachment assays to
      quantify the level of injury in our monolayers. We found a decrease in F-actin
      and an increase in deformability in TREK-1 deficient cells compared to control
      cells. Although total vinculin and focal adhesion kinase (FAK) levels remained
      unchanged, focal adhesions appeared to be less prominent and phosphorylation of
      FAK at the Tyr(925) residue was greater in TREK-1 deficient cells. TREK-1
      deficient cells have less F-actin and are more deformable making them more
      resistant to stretch-induced injury. 

PMID- 24586774
TI  - Impact of the Spanish smoke-free legislation on adult, non-smoker exposure to
      secondhand smoke: cross-sectional surveys before (2004) and after (2012)
      legislation.
AB  - BACKGROUND: In 2006, Spain implemented a national smoke-free legislation that
      prohibited smoking in enclosed public places and workplaces (except in
      hospitality venues). In 2011, it was extended to all hospitality venues and
      selected outdoor areas (hospital campuses, educational centers, and playgrounds).
      The objective of the study is to evaluate changes in exposure to secondhand smoke
      among the adult non-smoking population before the first law (2004-05) and after
      the second law (2011-12). METHODS: Repeated cross-sectional survey (2004-2005 and
      2011-2012) of a representative sample of the adult (>= 16 years) non-smoking
      population in Barcelona, Spain. We assess self-reported exposure to secondhand
      smoke (at home, the workplace, during leisure time, and in public/private
      transportation vehicles) and salivary cotinine concentration. RESULTS: Overall,
      the self-reported exposure to secondhand smoke fell from 75.7% (95%CI: 72.6 to
      78.8) in 2004-05 to 56.7% (95%CI: 53.4 to 60.0) in 2011-12. Self-reported
      exposure decreased from 32.5% to 27.6% (-15.1%, p<0.05) in the home, from 42.9%
      to 37.5% (-12.6%, p=0.11) at work/education venues, from 61.3% to 38.9% (-36.5%,
      p<0.001) during leisure time, and from 12.3% to 3.7% (-69.9%, p<0.001) in public
      transportation vehicles. Overall, the geometric mean of the salivary cotinine
      concentration in adult non-smokers fell by 87.2%, from 0.93 ng/mL at baseline to
      0.12 ng/mL after legislation (p<0.001). CONCLUSIONS: Secondhand smoke exposure
      among non-smokers, assessed both by self-reported exposure and salivary cotinine
      concentration, decreased after the implementation of a stepwise, comprehensive
      smoke-free legislation. There was a high reduction in secondhand smoke exposure
      during leisure time and no displacement of secondhand smoke exposure at home.

PMID- 24586775
TI  - Acute post-exercise myofibrillar protein synthesis is not correlated with
      resistance training-induced muscle hypertrophy in young men.
AB  - Muscle hypertrophy following resistance training (RT) involves activation of
      myofibrillar protein synthesis (MPS) to expand the myofibrillar protein pool. The
      degree of hypertrophy following RT is, however, highly variable and thus we
      sought to determine the relationship between the acute activation of MPS and RT
      induced hypertrophy. We measured MPS and signalling protein activation after the
      first session of resistance exercise (RE) in untrained men (n = 23) and then
      examined the relation between MPS with magnetic resonance image determined
      hypertrophy. To measure MPS, young men (24+/-1 yr; body mass index  = 26.4+/-0.9
      kg*m2) underwent a primed constant infusion of L-[ring-13C6] phenylalanine to
      measure MPS at rest, and acutely following their first bout of RE prior to 16 wk
      of RT. Rates of MPS were increased 235+/-38% (P<0.001) above rest 60-180 min post
      exercise and 184+/-28% (P = 0.037) 180-360 min post exercise. Quadriceps volume
      increased 7.9+/-1.6% (-1.9-24.7%) (P<0.001) after training. There was no
      correlation between changes in quadriceps muscle volume and acute rates of MPS
      measured over 1-3 h (r = 0.02), 3-6 h (r = 0.16) or the aggregate 1-6 h post
      exercise period (r = 0.10). Hypertrophy after chronic RT was correlated (r =
      0.42, P = 0.05) with phosphorylation of 4E-BP1(Thr37/46) at 1 hour post RE. We
      conclude that acute measures of MPS following an initial exposure to RE in
      novices are not correlated with muscle hypertrophy following chronic RT.

PMID- 24586776
TI  - Multiple sleep alterations in mice lacking cannabinoid type 1 receptors.
AB  - Cannabinoid type 1 (CB1) receptors are highly expressed in the brain and play a
      role in behavior control. Endogenous cannabinoid signaling is modulated by high
      fat diet (HFD). We investigated the consequences of congenital lack of CB1
      receptors on sleep in mice fed standard diet (SD) and HFD. CB1 cannabinoid
      receptor knock-out (KO) and wild-type (WT) mice were fed SD or HFD for 4 months
      (n = 9-10 per group). Mice were instrumented with electroencephalographic (EEG)
      and electromyographic electrodes. Recordings were performed during baseline (48
      hours), sleep deprivation (gentle handling, 6 hours), sleep recovery (18 hours),
      and after cage switch (insomnia model paradigm, 6 hours). We found multiple
      significant effects of genotype on sleep. In particular, KO spent more time awake
      and less time in non-rapid-eye-movement sleep (NREMS) and rapid-eye-movement
      sleep (REMS) than WT during the dark (active) period but not during the light
      (rest) period, enhancing the day-night variation of wake-sleep amounts. KO had
      slower EEG theta rhythm during REMS. REMS homeostasis after sleep deprivation was
      less effective in KO than in WT. Finally, KO habituated more rapidly to the
      arousing effect of the cage-switch test than WT. We did not find any significant
      effects of diet or of diet x genotype interaction on sleep. The occurrence of
      multiple sleep alterations in KO indicates important roles of CB1 cannabinoid
      receptors in limiting arousal during the active period of the day, in sleep
      regulation, and in sleep EEG in mice.

PMID- 24586777
TI  - Involvement of iron-evoked oxidative stress in smoking-related endothelial
      dysfunction in healthy young men.
AB  - BACKGROUND: Oxidative stress and smoking contribute to endothelial dysfunction.
      Iron might also play a role in oxidative stress generation and endothelial
      dysfunction. However, the involvement of iron in smoking-induced endothelial
      dysfunction in healthy smokers remains unclear. Therefore, we examined here
      whether (1) intravenous iron infusion impaired endothelial function evaluated by
      flow-mediated vasodilatation (FMD) in non-smokers, and (2) deferoxamine, a potent
      iron chelator, ameliorated endothelial dysfunction in healthy smokers. METHODS:
      Eight healthy young male non-smokers (23 +/- 4 years old) received intravenous
      injection of saccharated ferric oxide (0.7 mg/kg body weight), while 10 age
      matched healthy male smokers received deferoxamine mesylate (8.3 mg/kg body
      weight). At baseline, 5 and 20 minutes after treatment with iron or deferoxamine,
      biochemical variables were measured, including serum iron and marondialdehyde
      (MDA), a marker of lipid oxidation, and endothelial function was simultaneously
      evaluated by FMD. RESULTS: Compared with non-smokers, FMD was significantly lower
      in smokers. Iron and MDA levels were significantly increased, whereas FMD was
      impaired by iron infusion in non-smokers. Conversely, deferoxamine treatment
      significantly decreased iron and MDA levels and restored the decreased FMD in
      smokers. Baseline serum iron and MDA levels in all 18 subjects (non-smokers and
      smokers) were correlated with each other. There was a significant inverse
      correlation between the changes in MDA values and FMD from baseline in 18 men.
      Endothelium-independent vasodilation by glyceryl trinitrate was unaltered by
      either treatment. CONCLUSIONS: Our present study suggests that iron-evoked
      oxidative stress might play a role in endothelial dysfunction in healthy smokers.

PMID- 24586779
TI  - Impairment of Drosophila orthologs of the human orphan protein C19orf12 induces
      bang sensitivity and neurodegeneration.
AB  - Mutations in the orphan gene C19orf12 were identified as a genetic cause in a
      subgroup of patients with NBIA, a neurodegenerative disorder characterized by
      deposits of iron in the basal ganglia. C19orf12 was shown to be localized in
      mitochondria, however, nothing is known about its activity and no functional link
      exists to the clinical phenotype of the patients. This situation led us to
      investigate the effects of C19orf12 down-regulation in the model organism
      Drosophila melanogaster. Two genes are present in D. melanogaster, which are
      orthologs of C19orf12, CG3740 and CG11671. Here we provide evidence that
      transgenic flies with impaired C19orf12 homologs reflect the neurodegenerative
      phenotype and represent a valid tool to further analyze the pathomechanism in
      C19orf12-associated NBIA. 

PMID- 24586778
TI  - Organic cation transporter-mediated ergothioneine uptake in mouse neural
      progenitor cells suppresses proliferation and promotes differentiation into
      neurons.
AB  - The aim of the present study is to clarify the functional expression and
      physiological role in neural progenitor cells (NPCs) of carnitine/organic cation
      transporter OCTN1/SLC22A4, which accepts the naturally occurring food-derived
      antioxidant ergothioneine (ERGO) as a substrate in vivo. Real-time PCR analysis
      revealed that mRNA expression of OCTN1 was much higher than that of other organic
      cation transporters in mouse cultured cortical NPCs. Immunocytochemical analysis
      showed colocalization of OCTN1 with the NPC marker nestin in cultured NPCs and
      mouse embryonic carcinoma P19 cells differentiated into neural progenitor-like
      cells (P19-NPCs). These cells exhibited time-dependent [(3)H]ERGO uptake. These
      results demonstrate that OCTN1 is functionally expressed in murine NPCs. Cultured
      NPCs and P19-NPCs formed neurospheres from clusters of proliferating cells in a
      culture time-dependent manner. Exposure of cultured NPCs to ERGO or other
      antioxidants (edaravone and ascorbic acid) led to a significant decrease in the
      area of neurospheres with concomitant elimination of intracellular reactive
      oxygen species. Transfection of P19-NPCs with small interfering RNA for OCTN1
      markedly promoted formation of neurospheres with a concomitant decrease of
      [(3)H]ERGO uptake. On the other hand, exposure of cultured NPCs to ERGO markedly
      increased the number of cells immunoreactive for the neuronal marker betaIII
      tubulin, but decreased the number immunoreactive for the astroglial marker glial
      fibrillary acidic protein (GFAP), with concomitant up-regulation of neuronal
      differentiation activator gene Math1. Interestingly, edaravone and ascorbic acid
      did not affect such differentiation of NPCs, in contrast to the case of
      proliferation. Knockdown of OCTN1 increased the number of cells immunoreactive
      for GFAP, but decreased the number immunoreactive for betaIII-tubulin, with
      concomitant down-regulation of Math1 in P19-NPCs. Thus, OCTN1-mediated uptake of
      ERGO in NPCs inhibits cellular proliferation via regulation of oxidative stress,
      and also promotes cellular differentiation by modulating the expression of basic
      helix-loop-helix transcription factors via an unidentified mechanism different
      from antioxidant action. 

PMID- 24586780
TI  - Dynamic spatiotemporal trends of dengue transmission in the Asia-Pacific region,
      1955-2004.
AB  - BACKGROUND: Dengue fever (DF) is one of the most important emerging arboviral
      human diseases. Globally, DF incidence has increased by 30-fold over the last
      fifty years, and the geographic range of the virus and its vectors has expanded.
      The disease is now endemic in more than 120 countries in tropical and subtropical
      parts of the world. This study examines the spatiotemporal trends of DF
      transmission in the Asia-Pacific region over a 50-year period, and identified the
      disease's cluster areas. METHODOLOGY AND FINDINGS: The World Health
      Organization's DengueNet provided the annual number of DF cases in 16 countries
      in the Asia-Pacific region for the period 1955 to 2004. This fifty-year dataset
      was divided into five ten-year periods as the basis for the investigation of DF
      transmission trends. Space-time cluster analyses were conducted using scan
      statistics to detect the disease clusters. This study shows an increasing trend
      in the spatiotemporal distribution of DF in the Asia-Pacific region over the
      study period. Thailand, Vietnam, Laos, Singapore and Malaysia are identified as
      the most likely clusters (relative risk = 13.02) of DF transmission in this
      region in the period studied (1995 to 2004). The study also indicates that, for
      the most part, DF transmission has expanded southwards in the region.
      CONCLUSIONS: This information will lead to the improvement of DF prevention and
      control strategies in the Asia-Pacific region by prioritizing control efforts and
      directing them where they are most needed.

PMID- 24586781
TI  - Pathway analyses implicate glial cells in schizophrenia.
AB  - BACKGROUND: The quest to understand the neurobiology of schizophrenia and bipolar
      disorder is ongoing with multiple lines of evidence indicating abnormalities of
      glia, mitochondria, and glutamate in both disorders. Despite high heritability
      estimates of 81% for schizophrenia and 75% for bipolar disorder, compelling links
      between findings from neurobiological studies, and findings from large-scale
      genetic analyses, are only beginning to emerge. METHOD: Ten publically available
      gene sets (pathways) related to glia, mitochondria, and glutamate were tested for
      association to schizophrenia and bipolar disorder using MAGENTA as the primary
      analysis method. To determine the robustness of associations, secondary analyses
      were performed with: ALIGATOR, INRICH, and Set Screen. Data from the Psychiatric
      Genomics Consortium (PGC) were used for all analyses. There were 1,068,286 SNP
      level p-values for schizophrenia (9,394 cases/12,462 controls), and 2,088,878 SNP
      level p-values for bipolar disorder (7,481 cases/9,250 controls). RESULTS: The
      Glia-Oligodendrocyte pathway was associated with schizophrenia, after correction
      for multiple tests, according to primary analysis (MAGENTA p = 0.0005, 75%
      requirement for individual gene significance) and also achieved nominal levels of
      significance with INRICH (p = 0.0057) and ALIGATOR (p = 0.022). For bipolar
      disorder, Set Screen yielded nominally and method-wide significant associations
      to all three glial pathways, with strongest association to the Glia-Astrocyte
      pathway (p = 0.002). CONCLUSIONS: Consistent with findings of white matter
      abnormalities in schizophrenia by other methods of study, the Glia
      Oligodendrocyte pathway was associated with schizophrenia in our genomic study.
      These findings suggest that the abnormalities of myelination observed in
      schizophrenia are at least in part due to inherited factors, contrasted with the
      alternative of purely environmental causes (e.g. medication effects or
      lifestyle). While not the primary purpose of our study, our results also
      highlight the consequential nature of alternative choices regarding pathway
      analysis, in that results varied somewhat across methods, despite application to
      identical datasets and pathways.

PMID- 24586782
TI  - The status of rheumatoid factor and anti-cyclic citrullinated peptide antibody
      are not associated with the effect of anti-TNFalpha agent treatment in patients
      with rheumatoid arthritis: a meta-analysis.
AB  - OBJECTIVES: This meta-analysis was conducted to investigate whether the status of
      rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibody
      are associated with the clinical response to anti-tumor necrosis factor (TNF)
      alpha treatment in rheumatoid arthritis (RA). METHODS: A systemic literature
      review was performed using the MEDLINE, SCOPUS, Cochrane Library, ISI Web of
      Knowledge, and Clinical Trials Register databases, and Hayden's criteria of
      quality assessment for prognostic studies were used to evaluate all of the
      studies. The correlation between the RF and anti-CCP antibody status with the
      treatment effect of anti-TNFalpha agents was analyzed separately using the Mantel
      Haenszel method. A fixed-effects model was used when there was no significant
      heterogeneity; otherwise, a random-effects model was applied. Publication bias
      was assessed using Egger's linear regression and a funnel plot. RESULTS: A total
      of 14 studies involving 5561 RA patients meeting the inclusion criteria were
      included. The overall analysis showed that the pooled relative risk for the
      predictive effects of the RF and anti-CCP antibody status on patient response to
      anti-TNFalpha agents was 0.98 (95% CI: 0.91-1.05, p=0.54) and 0.88 (95% CI: 0.76
      1.03, p=0.11), respectively, with I(2) values of 43% (p=0.05) and 67% (p<0.01),
      respectively. Subgroup analyses of different anti-TNFalpha treatments (infliximab
      vs. etanercept vs. adalimumab vs. golimumab), response criteria (DAS28 vs. ACR20
      vs. EULAR response), follow-up period (>= 6 vs. <6 months), and ethnic group did
      not reveal a significant association for the status of RF and anti-CCP.
      CONCLUSIONS: Neither the RF nor anti-CCP antibody status in RA patients is
      associated with a clinical response to anti-TNFalpha treatment.

PMID- 24586783
TI  - Impact of HIV on CD8+ T cell CD57 expression is distinct from that of CMV and
      aging.
AB  - BACKGROUND: Chronic antigenic stimulation by cytomegalovirus (CMV) is thought to
      increase "immunosenesence" of aging, characterized by accumulation of terminally
      differentiated CD28- CD8+ T cells and increased CD57, a marker of proliferative
      history. Whether chronic HIV infection causes similar effects is currently
      unclear. METHODS: We compared markers of CD8+ T cell differentiation (e.g., CD28,
      CD27, CCR7, CD45RA) and CD57 expression on CD28- CD8+ T cells in healthy HIV
      uninfected adults with and without CMV infection and in both untreated and
      antiretroviral therapy (ART)-suppressed HIV-infected adults with asymptomatic CMV
      infection. RESULTS: Compared to HIV-uninfected adults without CMV (n=12), those
      with asymptomatic CMV infection (n=31) had a higher proportion of CD28-CD8+ T
      cells expressing CD57 (P=0.005). Older age was also associated with greater
      proportions of CD28-CD8+ T cells expressing CD57 (rho: 0.47, P=0.007). In
      contrast, untreated HIV-infected CMV+ participants (n=55) had much lower
      proportions of CD28- CD8+ cells expressing CD57 than HIV-uninfected CMV+
      participants (P<0.0001) and were enriched for less well-differentiated CD28-
      transitional memory (TTR) CD8+ T cells (P<0.0001). Chronically HIV-infected
      adults maintaining ART-mediated viral suppression (n=96) had higher proportions
      of CD28-CD8+ T cells expressing CD57 than untreated patients (P<0.0001), but
      continued to have significantly lower levels than HIV-uninfected controls
      (P=0.001). Among 45 HIV-infected individuals initiating their first ART regimen,
      the proportion of CD28-CD8+ T cells expressing CD57 declined (P<0.0001), which
      correlated with a decline in percent of transitional memory CD8+ T cells, and
      appeared to be largely explained by a decline in CD28-CD57- CD8+ T cell counts
      rather than an expansion of CD28-CD57+ CD8+ T cell counts. CONCLUSIONS: Unlike
      CMV and aging, which are associated with terminal differentiation and
      proliferation of effector memory CD8+ T cells, HIV inhibits this process,
      expanding less well-differentiated CD28- CD8+ T cells and decreasing the
      proportion of CD28- CD8+ T cells that express CD57.

PMID- 24586784
TI  - RNA CoMPASS: a dual approach for pathogen and host transcriptome analysis of RNA
      seq datasets.
AB  - High-throughput RNA sequencing (RNA-seq) has become an instrumental assay for the
      analysis of multiple aspects of an organism's transcriptome. Further, the
      analysis of a biological specimen's associated microbiome can also be performed
      using RNA-seq data and this application is gaining interest in the scientific
      community. There are many existing bioinformatics tools designed for analysis and
      visualization of transcriptome data. Despite the availability of an array of next
      generation sequencing (NGS) analysis tools, the analysis of RNA-seq data sets
      poses a challenge for many biomedical researchers who are not familiar with
      command-line tools. Here we present RNA CoMPASS, a comprehensive RNA-seq analysis
      pipeline for the simultaneous analysis of transcriptomes and metatranscriptomes
      from diverse biological specimens. RNA CoMPASS leverages existing tools and
      parallel computing technology to facilitate the analysis of even very large
      datasets. RNA CoMPASS has a web-based graphical user interface with intrinsic
      queuing to control a distributed computational pipeline. RNA CoMPASS was
      evaluated by analyzing RNA-seq data sets from 45 B-cell samples. Twenty-two of
      these samples were derived from lymphoblastoid cell lines (LCLs) generated by the
      infection of naive B-cells with the Epstein Barr virus (EBV), while another 23
      samples were derived from Burkitt's lymphomas (BL), some of which arose in part
      through infection with EBV. Appropriately, RNA CoMPASS identified EBV in all LCLs
      and in a fraction of the BLs. Cluster analysis of the human transcriptome
      component of the RNA CoMPASS output clearly separated the BLs (which have a
      germinal center-like phenotype) from the LCLs (which have a blast-like phenotype)
      with evidence of activated MYC signaling and lower interferon and NF-kB signaling
      in the BLs. Together, this analysis illustrates the utility of RNA CoMPASS in the
      simultaneous analysis of transcriptome and metatranscriptome data. RNA CoMPASS is
      freely available at http://rnacompass.sourceforge.net/. 

PMID- 24586785
TI  - Up-regulation of microRNA-190b plays a role for decreased IGF-1 that induces
      insulin resistance in human hepatocellular carcinoma.
AB  - BACKGROUND & AIMS: Insulin-like growth factor, (IGF)-1, is produced mainly by the
      liver and plays important roles in promoting growth and regulating metabolism.
      Previous study reported that development of hepatocellular carcinoma (HCC) was
      accompanied by a significant reduction in serum IGF-1 levels. Here, we
      hypothesized that dysregulation of microRNAs (miRNA) in HCC can modulate IGF-1
      expression post-transcriptionally. METHODS: The miRNAs expression profiles in a
      dataset of 29 HCC patients were examined using illumina BeadArray. Specific miRNA
      (miR)-190b, which was significantly up-regulated in HCC tumor tissues when
      compared with paired non-tumor tissues, was among those predicted to interact
      with 3'-untranslated region (UTR) of IGF-1. In order to explore the regulatory
      effects of miR-190b on IGF-1 expression, luciferase reporter assay, quantitative
      real-time PCR, western blotting and immunofluorecence analysis were performed in
      HCC cells. RESULTS: Overexpression of miR-190b in Huh7 cells attenuated the
      expression of IGF-1, whereas inhibition of miR-190b resulted in up-regulation of
      IGF-1. Restoration of IGF-1 expression reversed miR-190b-mediated impaired
      insulin signaling in Huh7 cells, supporting that IGF-1 was a direct and
      functional target of miR-190b. Additionally, low serum IGF-1 level was associated
      with insulin resistance and poor overall survival in HCC patients. CONCLUSIONS:
      Increased expression of miR-190 may cause decreased IGF-1 in HCC development.
      Insulin resistance appears to be a part of the physiopathologic significance of
      decreased IGF-1 levels in HCC progression. This study provides a novel miRNA
      mediated regulatory mechanism for controlling IGF-1 expression in HCC and
      elucidates the biological relevance of this interaction in HCC.

PMID- 24586786
TI  - Potential therapeutic competition in community-living older adults in the U.S.:
      use of medications that may adversely affect a coexisting condition.
AB  - OBJECTIVE: The 75% of older adults with multiple chronic conditions are at risk
      of therapeutic competition (i.e. treatment for one condition may adversely affect
      a coexisting condition). The objective was to determine the prevalence of
      potential therapeutic competition in community-living older adults. METHODS:
      Cross-sectional descriptive study of a representative sample of 5,815 community
      living adults 65 and older in the U.S, enrolled 2007-2009. The 14 most common
      chronic conditions treated with at least one medication were ascertained from
      Medicare claims. Medication classes recommended in national disease guidelines
      for these conditions and used by >= 2% of participants were identified from in
      person interviews conducted 2008-2010. Criteria for potential therapeutic
      competition included: 1), well-acknowledged adverse medication effect; 2) mention
      in disease guidelines; or 3) report in a systematic review or two studies
      published since 2000. Outcomes included prevalence of situations of potential
      therapeutic competition and frequency of use of the medication in individuals
      with and without the competing condition. RESULTS: Of 27 medication classes, 15
      (55.5%) recommended for one study condition may adversely affect other study
      conditions. Among 91 possible pairs of study chronic conditions, 25 (27.5%) have
      at least one potential therapeutic competition. Among participants, 1,313 (22.6%)
      received at least one medication that may worsen a coexisting condition; 753
      (13%) had multiple pairs of such competing conditions. For example, among 846
      participants with hypertension and COPD, 16.2% used a nonselective beta-blocker.
      In only 6 of 37 cases (16.2%) of potential therapeutic competition were those
      with the competing condition less likely to receive the medication than those
      without the competing condition. CONCLUSIONS: One fifth of older Americans
      receive medications that may adversely affect coexisting conditions. Determining
      clinical outcomes in these situations is a research and clinical priority.
      Effects on coexisting conditions should be considered when prescribing
      medications.

PMID- 24586787
TI  - The teratogenic effects of prenatal ethanol exposure are exacerbated by Sonic
      Hedgehog or GLI2 haploinsufficiency in the mouse.
AB  - Disruption of the Hedgehog signaling pathway has been implicated as an important
      molecular mechanism in the pathogenesis of fetal alcohol syndrome. In severe
      cases, the abnormalities of the face and brain that result from prenatal ethanol
      exposure fall within the spectrum of holoprosencephaly. Single allele mutations
      in the Hh pathway genes Sonic Hedgehog (SHH) and GLI2 cause holoprosencephaly
      with extremely variable phenotypic penetrance in humans. Here, we tested whether
      mutations in these genes alter the frequency or severity of ethanol-induced
      dysmorphology in a mouse model. Timed pregnancies were established by mating
      Shh(+/-) or Gli2(+/-) male mice backcrossed to C57BL/6J strain, with wildtype
      females. On gestational day 7, dams were treated with two i.p. doses of 2.9 g/kg
      ethanol (or vehicle alone), administered four hrs apart. Fetuses were then
      genotyped and imaged, and the severity of facial dysmorphology was assessed.
      Following ethanol exposure, mean dysmorphology scores were increased by 3.2- and
      6.6-fold in Shh(+/-) and Gli2(+/-) groups, respectively, relative to their
      wildtype littermates. Importantly, a cohort of heterozygous fetuses exhibited
      phenotypes not typically produced in this model but associated with severe
      holoprosencephaly, including exencephaly, median cleft lip, otocephaly, and
      proboscis. As expected, a correlation between the severity of facial
      dysmorphology and medial forebrain deficiency was observed in affected animals.
      While Shh(+/-) and Gli2(+/-) mice have been described as phenotypically normal,
      these results illustrate a functional haploinsufficiency of both genes in
      combination with ethanol exposure. By demonstrating an interaction between
      specific genetic and environmental risk factors, this study provides important
      insights into the multifactorial etiology and complex pathogenesis of fetal
      alcohol syndrome and holoprosencephaly.

PMID- 24586789
TI  - Galantamine slows down plaque formation and behavioral decline in the 5XFAD mouse
      model of Alzheimer's disease.
AB  - The plant alkaloid galantamine is an established symptomatic drug treatment for
      Alzheimer's disease (AD), providing temporary cognitive and global relief in
      human patients. In this study, the 5X Familial Alzheimer's Disease (5XFAD) mouse
      model was used to investigate the effect of chronic galantamine treatment on
      behavior and amyloid beta (Abeta) plaque deposition in the mouse brain.
      Quantification of plaques in untreated 5XFAD mice showed a gender specific
      phenotype; the plaque density increased steadily reaching saturation in males
      after 10 months of age, whereas in females the density further increased until
      after 14 months of age. Moreover, females consistently displayed a higher plaque
      density in comparison to males of the same age. Chronic oral treatment with
      galantamine resulted in improved performance in behavioral tests, such as open
      field and light-dark avoidance, already at mildly affected stages compared to
      untreated controls. Treated animals of both sexes showed significantly lower
      plaque density in the brain, i.e., the entorhinal cortex and hippocampus, gliosis
      being always positively correlated to plaque load. A high dose treatment with a
      daily uptake of 26 mg/kg body weight was tolerated well and produced
      significantly larger positive effects than a lower dose treatment (14 mg/kg body
      weight) in terms of plaque density and behavior. These results strongly support
      that galantamine, in addition to improving cognitive and behavioral symptoms in
      AD, may have disease-modifying and neuroprotective properties, as is indicated by
      delayed Abeta plaque formation and reduced gliosis. 

PMID- 24586790
TI  - Decreased plasma brain-derived neurotrophic factor and vascular endothelial
      growth factor concentrations during military training.
AB  - Decreased concentrations of plasma brain-derived neurotrophic factor (BDNF) and
      serum BDNF have been proposed to be a state marker of depression and a biological
      indicator of loaded psychosocial stress. Stress evaluations of participants in
      military mission are critically important and appropriate objective biological
      parameters that evaluate stress are needed. In military circumstances, there are
      several problems to adopt plasma BDNF concentration as a stress biomarker. First,
      in addition to psychosocial stress, military missions inevitably involve physical
      exercise that increases plasma BDNF concentrations. Second, most participants in
      the mission do not have adequate quality or quantity of sleep, and sleep
      deprivation has also been reported to increase plasma BDNF concentration. We
      evaluated plasma BDNF concentrations in 52 participants on a 9-week military
      mission. The present study revealed that plasma BDNF concentration significantly
      decreased despite elevated serum enzymes that escaped from muscle and decreased
      quantity and quality of sleep, as detected by a wearable watch-type sensor. In
      addition, we observed a significant decrease in plasma vascular endothelial
      growth factor (VEGF) during the mission. VEGF is also neurotrophic and its
      expression in the brain has been reported to be up-regulated by antidepressive
      treatments and down-regulated by stress. This is the first report of decreased
      plasma VEGF concentrations by stress. We conclude that decreased plasma
      concentrations of neurotrophins can be candidates for mental stress indicators in
      actual stressful environments that include physical exercise and limited sleep. 

PMID- 24586788
TI  - The ubiquitin ligase ASB4 promotes trophoblast differentiation through the
      degradation of ID2.
AB  - Vascularization of the placenta is a critical developmental process that ensures
      fetal viability. Although the vascular health of the placenta affects both
      maternal and fetal well being, relatively little is known about the early stages
      of placental vascular development. The ubiquitin ligase Ankyrin repeat, SOCS box
      containing 4 (ASB4) promotes embryonic stem cell differentiation to vascular
      lineages and is highly expressed early in placental development. The
      transcriptional regulator Inhibitor of DNA binding 2 (ID2) negatively regulates
      vascular differentiation during development and is a target of many ubiquitin
      ligases. Due to their overlapping spatiotemporal expression pattern in the
      placenta and contrasting effects on vascular differentiation, we investigated
      whether ASB4 regulates ID2 through its ligase activity in the placenta and
      whether this activity mediates vascular differentiation. In mouse placentas, ASB4
      expression is restricted to a subset of cells that express both stem cell and
      endothelial markers. Placentas that lack Asb4 display immature vascular
      patterning and retain expression of placental progenitor markers, including ID2
      expression. Using JAR placental cells, we determined that ASB4 ubiquitinates and
      represses ID2 expression in a proteasome-dependent fashion. Expression of ASB4 in
      JAR cells and primary isolated trophoblast stem cells promotes the expression of
      differentiation markers. In functional endothelial co-culture assays, JAR cells
      ectopically expressing ASB4 increased endothelial cell turnover and stabilized
      endothelial tube formation, both of which are hallmarks of vascular
      differentiation within the placenta. Co-transfection of a degradation-resistant
      Id2 mutant with Asb4 inhibits both differentiation and functional responses.
      Lastly, deletion of Asb4 in mice induces a pathology that phenocopies human pre
      eclampsia, including hypertension and proteinuria in late-stage pregnant females.
      These results indicate that ASB4 mediates vascular differentiation in the
      placenta via its degradation of ID2. 

PMID- 24586791
TI  - A semi-automated pipeline for the segmentation of rhesus macaque hippocampus:
      validation across a wide age range.
AB  - This report outlines a neuroimaging pipeline that allows a robust, high
      throughput, semi-automated, template-based protocol for segmenting the
      hippocampus in rhesus macaque (Macaca mulatta) monkeys ranging from 1 week to 260
      weeks of age. The semiautomated component of this approach minimizes user effort
      while concurrently maximizing the benefit of human expertise by requiring as few
      as 10 landmarks to be placed on images of each hippocampus to guide registration.
      Any systematic errors in the normalization process are corrected using a machine
      learning algorithm that has been trained by comparing manual and automated
      segmentations to identify systematic errors. These methods result in high spatial
      overlap and reliability when compared with the results of manual tracing
      protocols. They also dramatically reduce the time to acquire data, an important
      consideration in large-scale neuroradiological studies involving hundreds of MRI
      scans. Importantly, other than the initial generation of the unbiased template,
      this approach requires only modest neuroanatomical training. It has been
      validated for high-throughput studies of rhesus macaque hippocampal anatomy
      across a broad age range. 

PMID- 24586792
TI  - Behavioral and socioeconomic risk factors associated with probable resistance to
      ceftriaxone and resistance to penicillin and tetracycline in Neisseria
      gonorrhoeae in Shanghai.
AB  - Globally, incidence of Neisseria gonorrhoeae infection is once again the highest
      of the bacterial sexually transmitted infections. The bacterium can produce
      serious complications in those infected, and emerging resistance to third
      generation cephalosporins could usher in an era of potentially untreatable
      gonorrhea. This research aimed to identify risk factors for antibiotic resistant
      gonorrhea infection among clients at a Shanghai sexually transmitted infection
      clinic over two time periods, 2004-2005 and 2008-2011. Demographic and risk
      factor behavior data, and biological samples for antimicrobial resistance
      analysis, were collected. Statistical models were built to identify risk factors
      associated with probable resistance to ceftriaxone and resistance to penicillin
      and tetracycline. High levels of ciprofloxacin resistance (98%) in our sample
      precluded examining its risk factors; all isolates were susceptible to
      spectinomycin. Overall (P<0.001), chromosomal (P<0.001), and plasmid-mediated (P
      = 0.01) penicillin resistance decreased from the first to second period of the
      study. For tetracycline, chromosomal resistance decreased (P = 0.01) and plasmid
      mediated resistance increased (P<0.001) between the first and second periods of
      study. In multi-level multivariable regression models, male gender (P = 0.03) and
      older age (P = 0.01) were associated with increased minimum inhibitory
      concentrations to ceftriaxone. Male gender (P = 0.03) and alcohol use (P = 0.02)
      were associated with increased odds of overall tetracycline resistance. Male
      gender was associated with increased odds of chromosomally-mediated tetracycline
      resistance (P = 0.04), and alcohol use was associated with increased odds of
      plasmid-mediated tetracycline resistance (P = 0.02). Additionally, individuals in
      middle-salary categories were found to have lower odds of plasmid-mediated
      resistance to tetracycline compared with those in the lowest salary category
      (P<=0.02). This study is one of the first to use multilevel analysis to consider
      the association between risk factors for gonorrhea infections and mechanisms of
      resistance to individual antibiotics. Such information is urgently needed to
      combat the growing threat of untreatable gonorrhea. 

PMID- 24586793
TI  - Molecular recognition in complexes of TRF proteins with telomeric DNA.
AB  - Telomeres are specialized nucleoprotein assemblies that protect the ends of
      linear chromosomes. In humans and many other species, telomeres consist of tandem
      TTAGGG repeats bound by a protein complex known as shelterin that remodels
      telomeric DNA into a protective loop structure and regulates telomere
      homeostasis. Shelterin recognizes telomeric repeats through its two major
      components known as Telomere Repeat-Binding Factors, TRF1 and TRF2. These two
      homologous proteins are therefore essential for the formation and normal function
      of telomeres. Indeed, TRF1 and TRF2 are implicated in a plethora of different
      cellular functions and their depletion leads to telomere dysfunction with
      chromosomal fusions, followed by apoptotic cell death. More specifically, it was
      found that TRF1 acts as a negative regulator of telomere length, and TRF2 is
      involved in stabilizing the loop structure. Consequently, these proteins are of
      great interest, not only because of their key role in telomere maintenance and
      stability, but also as potential drug targets. In the current study, we
      investigated the molecular basis of telomeric sequence recognition by TRF1 and
      TRF2 and their DNA binding mechanism. We used molecular dynamics (MD) to
      calculate the free energy profiles for binding of TRFs to telomeric DNA. We found
      that the predicted binding free energies were in good agreement with experimental
      data. Further, different molecular determinants of binding, such as binding
      enthalpies and entropies, the hydrogen bonding pattern and changes in surface
      area, were analyzed to decompose and examine the overall binding free energies at
      the structural level. With this approach, we were able to draw conclusions
      regarding the consecutive stages of sequence-specific association, and propose a
      novel aspartate-dependent mechanism of sequence recognition. Finally, our work
      demonstrates the applicability of computational MD-based methods to studying
      protein-DNA interactions. 

PMID- 24586794
TI  - A developmental approach to predicting neuronal connectivity from small
      biological datasets: a gradient-based neuron growth model.
AB  - Relating structure and function of neuronal circuits is a challenging problem. It
      requires demonstrating how dynamical patterns of spiking activity lead to
      functions like cognitive behaviour and identifying the neurons and connections
      that lead to appropriate activity of a circuit. We apply a "developmental
      approach" to define the connectome of a simple nervous system, where connections
      between neurons are not prescribed but appear as a result of neuron growth. A
      gradient based mathematical model of two-dimensional axon growth from rows of
      undifferentiated neurons is derived for the different types of neurons in the
      brainstem and spinal cord of young tadpoles of the frog Xenopus. Model parameters
      define a two-dimensional CNS growth environment with three gradient cues and the
      specific responsiveness of the axons of each neuron type to these cues. The model
      is described by a nonlinear system of three difference equations; it includes a
      random variable, and takes specific neuron characteristics into account.
      Anatomical measurements are first used to position cell bodies in rows and define
      axon origins. Then a generalization procedure allows information on the axons of
      individual neurons from small anatomical datasets to be used to generate larger
      artificial datasets. To specify parameters in the axon growth model we use a
      stochastic optimization procedure, derive a cost function and find the optimal
      parameters for each type of neuron. Our biologically realistic model of axon
      growth starts from axon outgrowth from the cell body and generates multiple axons
      for each different neuron type with statistical properties matching those of real
      axons. We illustrate how the axon growth model works for neurons with axons which
      grow to the same and the opposite side of the CNS. We then show how, by adding a
      simple specification for dendrite morphology, our model "developmental approach"
      allows us to generate biologically-realistic connectomes. 

PMID- 24586795
TI  - Evidence that HIV-1 CRF01_AE is associated with low CD4+T cell count and CXCR4 co
      receptor usage in recently infected young men who have sex with men (MSM) in
      Shanghai, China.
AB  - Men who have sex with men (MSM) have recently accounted for an alarmingly
      increasing proportion of HIV-1 transmission in China. In order to investigate the
      immune status as a result of CRF01_AE infection and CXCR4 co-receptor usage in a
      young Shanghai-based HIV-1-infected MSM population in Shanghai, 364 HIV-1
      infected MSM with average age of 22.7 years old, newly diagnosed between Jan 2009
      and Jul 2013 were analyzed for CD4+T cell count, subtyping using phylogenetic
      analysis, and viral co-receptor tropism using Geno2pheno and webPSSM in
      combination. A total of 276 individuals were identified as recently infected.
      Subtype assignment were as follows: 176 (63.8%) CRF01_AE, 77 (27.9%) CRF07_BC,
      and 23 (8.3%) subtype B. Besides, 24 second-generation recombinant strains were
      identified. A lower CD4+T cell count at baseline survey was observed among
      CRF01_AE strain-infected individuals, compared to those who were infected with
      CRF07_BC (P<0.01). The frequency of baseline CD4+T cell count <200 was higher and
      the frequency of CD4 T counts >500 lower in CRF01_AE infection than CRF07_BC
      infection. It is worth noting that 32.4%-40.9% of CRF01_AE strain-infected
      individuals were predicted to carry CXCR4-tropic viruses whereas none of CRF07_BC
      and subtype B were found to be as CXCR4-tropic viruses (P<0.001). As could be
      expected CXCR4 tropism was associated with lower CD4 T counts. This study
      revealed that CRF01_AE strains with high frequency of CXCR4 tropism are
      prevailing in the young MSM population in China and could potentially cause a
      severe loss of CD4+T cell count and rapid disease progression. A regular
      surveillance of HIV-1 subtypes, CD4+T cell count and viral co-receptor usage
      would be greatly beneficial for effectively monitoring disease progression,
      improvement of antiretroviral therapy strategy and prompt intervention of
      transmission. 

PMID- 24586796
TI  - Effect of age on complexity and causality of the cardiovascular control:
      comparison between model-based and model-free approaches.
AB  - The proposed approach evaluates complexity of the cardiovascular control and
      causality among cardiovascular regulatory mechanisms from spontaneous variability
      of heart period (HP), systolic arterial pressure (SAP) and respiration (RESP). It
      relies on construction of a multivariate embedding space, optimization of the
      embedding dimension and a procedure allowing the selection of the components most
      suitable to form the multivariate embedding space. Moreover, it allows the
      comparison between linear model-based (MB) and nonlinear model-free (MF)
      techniques and between MF approaches exploiting local predictability (LP) and
      conditional entropy (CE). The framework was applied to study age-related
      modifications of complexity and causality in healthy humans in supine resting
      (REST) and during standing (STAND). We found that: 1) MF approaches are more
      efficient than the MB method when nonlinear components are present, while the
      reverse situation holds in presence of high dimensional embedding spaces; 2) the
      CE method is the least powerful in detecting age-related trends; 3) the
      association of HP complexity on age suggests an impairment of cardiac regulation
      and response to STAND; 4) the relation of SAP complexity on age indicates a
      gradual increase of sympathetic activity and a reduced responsiveness of
      vasomotor control to STAND; 5) the association from SAP to HP on age during STAND
      reveals a progressive inefficiency of baroreflex; 6) the reduced connection from
      HP to SAP with age might be linked to the progressive exploitation of Frank
      Starling mechanism at REST and to the progressive increase of peripheral
      resistances during STAND; 7) at REST the diminished association from RESP to HP
      with age suggests a vagal withdrawal and a gradual uncoupling between respiratory
      activity and heart; 8) the weakened connection from RESP to SAP with age might be
      related to the progressive increase of left ventricular thickness and vascular
      stiffness and to the gradual decrease of respiratory sinus arrhythmia. 

PMID- 24586798
TI  - Inhibition of human and yeast 20S proteasome by analogues of trypsin inhibitor
      SFTI-1.
AB  - Starting from the primary structure of sunflower trypsin inhibitor SFTI-1, we
      designed novel non-covalent inhibitors of human and yeast 20S proteasomes.
      Peptides with Arg residue in P1 position and two basic amino acid residues (Lys
      or/and Arg) in P2' and P3' positions strongly inhibited chymotrypsin-like and
      caspase-like activities, while trypsin-like activity was poorly modified. We
      found that some SFTI-1 analogues up-regulated exclusively the chymotrypsin-like
      activity of latent yeast 20S proteasome. 

PMID- 24586797
TI  - PIAS1 regulates breast tumorigenesis through selective epigenetic gene silencing.
AB  - Epigenetic gene silencing by histone modifications and DNA methylation is
      essential for cancer development. The molecular mechanism that promotes selective
      epigenetic changes during tumorigenesis is not understood. We report here that
      the PIAS1 SUMO ligase is involved in the progression of breast tumorigenesis.
      Elevated PIAS1 expression was observed in breast tumor samples. PIAS1 knockdown
      in breast cancer cells reduced the subpopulation of tumor-initiating cells, and
      inhibited breast tumor growth in vivo. PIAS1 acts by delineating histone
      modifications and DNA methylation to silence the expression of a subset of
      clinically relevant genes, including breast cancer DNA methylation signature
      genes such as cyclin D2 and estrogen receptor, and breast tumor suppressor WNT5A.
      Our studies identify a novel epigenetic mechanism that regulates breast
      tumorigenesis through selective gene silencing. 

PMID- 24586799
TI  - DrugScorePPI knowledge-based potentials used as scoring and objective function in
      protein-protein docking.
AB  - The distance-dependent knowledge-based DrugScore(PPI) potentials, previously
      developed for in silico alanine scanning and hot spot prediction on given
      structures of protein-protein complexes, are evaluated as a scoring and objective
      function for the structure prediction of protein-protein complexes. When applied
      for ranking "unbound perturbation" ("unbound docking") decoys generated by Baker
      and coworkers a 4-fold (1.5-fold) enrichment of acceptable docking solutions in
      the top ranks compared to a random selection is found. When applied as an
      objective function in FRODOCK for bound protein-protein docking on 97 complexes
      of the ZDOCK benchmark 3.0, DrugScore(PPI)/FRODOCK finds up to 10% (15%) more
      high accuracy solutions in the top 1 (top 10) predictions than the original
      FRODOCK implementation. When used as an objective function for global unbound
      protein-protein docking, fair docking success rates are obtained, which improve
      by ~ 2-fold to 18% (58%) for an at least acceptable solution in the top 10 (top
      100) predictions when performing knowledge-driven unbound docking. This suggests
      that DrugScore(PPI) balances well several different types of interactions
      important for protein-protein recognition. The results are discussed in view of
      the influence of crystal packing and the type of protein-protein complex docked.
      Finally, a simple criterion is provided with which to estimate a priori if
      unbound docking with DrugScore(PPI)/FRODOCK will be successful.

PMID- 24586800
TI  - Biophysical controls on light response of net CO2 exchange in a winter wheat
      field in the North China Plain.
AB  - To investigate the impacts of biophysical factors on light response of net
      ecosystem exchange (NEE), CO2 flux was measured using the eddy covariance
      technique in a winter wheat field in the North China Plain from 2003 to 2006. A
      rectangular hyperbolic function was used to describe NEE light response. Maximum
      photosynthetic capacity (P max) was 46.6 +/- 4.0 umol CO2 m(-2) s(-1) and initial
      light use efficiency (alpha) 0.059 +/- 0.006 umol umol(-1) in April-May, two or
      three times as high as those in March. Stepwise multiple linear regressions
      showed that P max increased with the increase in leaf area index (LAI), canopy
      conductance (g c) and air temperature (T a) but declined with increasing vapor
      pressure deficit (VPD) (P<0.001). The factors influencing P max were sorted as
      LAI, g c, T a and VPD. alpha was proportional to ln(LAI), g c, T a and VPD
      (P<0.001). The effects of LAI, g c and T a on alpha were larger than that of VPD.
      When T a>25 degrees C or VPD>1.1-1.3 kPa, NEE residual increased with the
      increase in T a and VPD (P<0.001), indicating that temperature and water stress
      occurred. When g c was more than 14 mm s(-1) in March and May and 26 mm s(-1) in
      April, the NEE residuals decline disappeared, or even turned into an increase in
      g c (P<0.01), implying shifts from stomatal limitation to non-stomatal limitation
      on NEE. Although the differences between sunny and cloudy sky conditions were
      unremarkable for light response parameters, simulated net CO2 uptake under the
      same radiation intensity averaged 18% higher in cloudy days than in sunny days
      during the year 2003-2006. It is necessary to include these effects in relevant
      carbon cycle models to improve our estimation of carbon balance at regional and
      global scales.

PMID- 24586802
TI  - STK31/TDRD8, a germ cell-specific factor, is dispensable for reproduction in
      mice.
AB  - Tudor domain containing (Tdrd) proteins that are expressed in germ cells are
      divided into two groups. One group, consisting of TDRD1, TDRKH, TDRD9 and TDRD12,
      function in piRNA biogenesis and retrotransposon silencing, while the other group
      including RNF17/TDRD4 and TDRD5-7 are required for spermiogenesis. These Tdrd
      proteins play distinct roles during male germ cell development. Here, we report
      the characterization of STK31/TDRD8 in mice. STK31 contains a tudor domain and a
      serine/threonine kinase domain. We find that STK31 is a cytoplasmic protein in
      germ cells. STK31 is expressed in embryonic gonocytes of both sexes and postnatal
      spermatocytes and round spermatids in males. Disruption of the tudor domain and
      kinase domain of STK31 respectively does not affect fertility in mice. Our data
      suggest that the function of STK31 may be redundant with other Tdrd proteins in
      germ cell development. 

PMID- 24586801
TI  - Analytic programming with FMRI data: a quick-start guide for statisticians using
      R.
AB  - Functional magnetic resonance imaging (fMRI) is a thriving field that plays an
      important role in medical imaging analysis, biological and neuroscience research
      and practice. This manuscript gives a didactic introduction to the statistical
      analysis of fMRI data using the R project, along with the relevant R code. The
      goal is to give statisticians who would like to pursue research in this area a
      quick tutorial for programming with fMRI data. References of relevant packages
      and papers are provided for those interested in more advanced analysis. 

PMID- 24586803
TI  - Phosphorus metabolic disorder of Guizhou semi-fine wool sheep.
AB  - Guizhou semi-fine wool sheep are affected by a disease, characterized by
      emaciation, lameness, stiffness in the gait, enlargement of the costochondral
      junctions, and abnormal curvature in the long bones. The objective of this study
      was to determine possible relationships between the disease and mineral
      deficiencies. Samples of tissue and blood were collected from affected and
      unaffected sheep. Samples of soil and forage were collected from affected and
      unaffected areas. The samples were used for biochemical analyses and mineral
      nutrient measurements. Results showed that phosphorus (P) concentrations in
      forage samples from affected areas were significantly lower than those from
      unaffected areas (P < 0.01) and the mean ratio of calcium (Ca) to P in the
      affected forage was 12:1. Meanwhile, P concentrations of blood, bone, tooth, and
      wool from the affected sheep were also significantly lower than those from the
      unaffected group (P < 0.01). Serum P levels of the affected animals were much
      lower than those of the unaffected ones, whereas serum alkaline phosphatase
      levels from the affected were significantly higher than those from the unaffected
      (P < 0.01). Inorganic P levels of the affected sheep were about half of those in
      the control group. Oral administration of disodium hydrogen phosphate prevented
      and cured the disease. The study clearly demonstrated that the disease of Guizhou
      semi-fine wool sheep was mainly caused by the P deficiency in forage, as a result
      of fenced pasture and animal habitat fragmentation. 

PMID- 24586804
TI  - Modulation of Anopheles stephensi gene expression by nitroquine, an antimalarial
      drug against Plasmodium yoelii infection in the mosquito.
AB  - BACKGROUND: Antimalarial drugs may impact mosquito's defense against Plasmodium
      parasites. Our previous study showed nitroquine significantly reduced infection
      of Anopheles stephensi by Plasmodium yoelii, but the underlying mechanism remains
      unclear. In order to understand how transmission capacity of An. stephensi was
      affected by nitroquine, we explored the transcriptome of adult females after
      different treatments, examined changes in gene expression profiles, and
      identified transcripts affected by the drug and parasite. METHODOLOGY/PRINCIPAL
      FINDINGS: We extended massively parallel sequencing and data analysis (including
      gene discovery, expression profiling, and function prediction) to An. stephensi
      before and after Plasmodium infection with or without nitroquine treatment. Using
      numbers of reads assembled into specific contigs to calculate relative abundances
      (RAs), we categorized the assembled contigs into four groups according to the
      differences in RA values infection induced, infection suppressed, drug induced,
      and drug suppressed. We found both nitroquine in the blood meal and Plasmodium
      infection altered transcription of mosquito genes implicated in diverse
      processes, including pathogen recognition, signal transduction, prophenoloxidase
      activation, cytoskeleton assembling, cell adhesion, and oxidative stress. The
      differential gene expression may have promoted certain defense responses of An.
      stephensi against the parasite and decreased its infectivity.
      CONCLUSIONS/SIGNIFICANCE: Our study indicated that nitroquine may regulate
      several immune mechanisms at the level of gene transcription in the mosquito
      against Plasmodium infection. This highlights the need for better understanding
      of antimalarial drug's impact on parasite survival and transmission. In addition,
      our data largely enriched the existing sequence information of An. stephensi, an
      epidemiologically important vector species.

PMID- 24586806
TI  - Effect of bacteria on the wound healing behavior of oral epithelial cells.
AB  - Wounded tissue offers opportunity to microflora to adhere, colonize, invade and
      infect surrounding healthy tissue. The bacteria of the oral cavity have the
      potential to alter the wound healing process by interacting with keratinocytes.
      The aim of this study was to investigate mechanisms through which oral bacteria
      may influence re-epithelialization by interacting with gingival keratinocytes. By
      an in vitro scratch assay we demonstrate that primary gingival keratinocytes have
      impaired closure when exposed to two well characterized oral bacteria, P.
      gingivalis, and to a lesser extent, F. nucleatum. P. gingivalis reduced wound
      closure by ~ 40%, which was partially dependent on proteolytic activity, and
      bacteria was still present within infected cells 9 days later despite exposure to
      bacteria for only 24 h. Both oral bacteria caused keratinocyte apoptosis at the
      wound site with cell death being greatest at the wound edge. P. gingivalis and F.
      nucleatum adversely affected cell proliferation and the effect also had a spatial
      component being most striking at the edge. The impact of the bacteria was long
      lasting even when exposure was brief. Cell migration was compromised in bacteria
      challenged keratinocytes with P. gingivalis having more severe effect (p<0.05)
      than F. nucleatum. Quantitative real time PCR of bacteria challenged cells showed
      that P. gingivalis and to a lesser extent F. nucleatum significantly
      downregulated cell cycle genes cyclin1, CDK1, and CDK4 (p<0.05) that are critical
      for GI/S transition. Further, genes associated with cell migration such as
      integrin beta-3 and -6 were significantly downregulated by P. gingivalis
      (p<0.05).

PMID- 24586805
TI  - Circulating tumor cells as a biomarker of response to treatment in patient
      derived xenograft mouse models of pancreatic adenocarcinoma.
AB  - Circulating tumor cells (CTCs) are cells shed from solid tumors into circulation
      and have been shown to be prognostic in the setting of metastatic disease. These
      cells are obtained through a routine blood draw and may serve as an easily
      accessible marker for monitoring treatment effectiveness. Because of the rapid
      progression of pancreatic ductal adenocarcinoma (PDAC), early insight into
      treatment effectiveness may allow for necessary and timely changes in treatment
      regimens. The objective of this study was to evaluate CTC burden as a biomarker
      of response to treatment with a oral phosphatidylinositol-3-kinase inhibitor,
      BKM120, in patient-derived xenograft (PDX) mouse models of PDAC. PDX mice were
      randomized to receive vehicle or BKM120 treatment for 28 days and CTCs were
      enumerated from whole blood before and after treatment using a microfluidic chip
      that selected for EpCAM (epithelial cell adhesion molecule) positive cells. This
      microfluidic device allowed for the release of captured CTCs and enumeration of
      these cells via their electrical impedance signatures. Median CTC counts
      significantly decreased in the BKM120 group from pre- to post-treatment (26.61 to
      2.21 CTCs/250 uL, p = 0.0207) while no significant change was observed in the
      vehicle group (23.26 to 11.89 CTCs/250 uL, p = 0.8081). This reduction in CTC
      burden in the treatment group correlated with tumor growth inhibition indicating
      CTC burden is a promising biomarker of response to treatment in preclinical
      models. Mutant enriched sequencing of isolated CTCs confirmed that they harbored
      KRAS G12V mutations, identical to the matched tumors. In the long-term, PDX mice
      are a useful preclinical model for furthering our understanding of CTCs.
      Clinically, mutational analysis of CTCs and serial monitoring of CTC burden may
      be used as a minimally invasive approach to predict and monitor treatment
      response to guide therapeutic regimens. 

PMID- 24586807
TI  - The effects of fruiting positions on cellulose synthesis and sucrose metabolism
      during cotton (Gossypium hirsutum L.) fiber development.
AB  - Cotton (Gossypium hirsutum L.) boll positions on a fruiting branch vary in their
      contribution to yield and fiber quality. Fiber properties are dependent on
      deposition of cellulose in the fiber cell wall, but information about the
      enzymatic differences in sucrose metabolism between these fruiting positions is
      lacking. Therefore, two cotton cultivars with different sensitivities to low
      temperature were tested in 2010 and 2011 to quantify the effect of fruit
      positions (FPs) on fiber quality in relation to sucrose content, enzymatic
      activities and sucrose metabolism. The indices including sucrose content, sucrose
      transformation rate, cellulose content, and the activities of the key enzymes,
      sucrose phosphate synthase (SPS), acid invertase (AI) and sucrose synthase (SuSy)
      which inhibit cellulose synthesis and eventually affect fiber quality traits in
      cotton fiber, were determined. Results showed that as compared with those of FP1,
      cellulose content, sucrose content, and sucrose transformation rate of FP3 were
      all decreased, and the variations of cellulose content and sucrose transformation
      rate caused by FPs in Sumian 15 were larger than those in Kemian 1. Under FP
      effect, activities of SPS and AI in sucrose regulation were decreased, while SuSy
      activity in sucrose degradation was increased. The changes in activities of SuSy
      and SPS in response to FP effect displayed different and large change ranges
      between the two cultivars. These results indicate that restrained cellulose
      synthesis and sucrose metabolism in distal FPs are mainly attributed to the
      changes in the activities of these enzymes. The difference in fiber quality,
      cellulose synthesis and sucrose metabolism in response to FPs in fiber cells for
      the two cotton cultivars was mainly determined by the activities of both SuSy and
      SPS.

PMID- 24586808
TI  - Differential effects of furnidipines' metabolites on reperfusion-induced
      arrhythmias in rats in vivo.
AB  - We previously established that furnidipine (FUR) and oxy dihydropyridines prevent
      rats mortality by strong reduction of the lethal arrhythmias in reperfusion.
      Therefore we decided to study the influence of three main metabolites (M-2, M-3,
      M-8) of FUR on ischemia-and reperfusion- induced arrhythmias and hemodynamic
      parameters in rat model to examine their independent activity. The metabolites (M
      2, M-3, M-8) were given orally 20 mg/kg (24 and 1 h before ischemia). Mortality
      was significantly diminished in M-2 and M-3 treated groups with M-3 preventing
      animal mortality entirely. All three examined substances significantly reduced
      the duration and incidence of ventricular fibrillation (VF) with M-3, once again,
      completely preventing VF. Moreover, only M-3 significantly decreased the duration
      of ventricular tachycardia but had no influence on their incidence. Through the
      occlusion and reperfusion periods, M-2 and M-3 were markedly less hypotensive
      than M-8 and did not influence on heart rate. We conclude that two tested
      metabolites of FUR, M-3 and M-2 exhibited the most pronounced anti-arrhythmic
      effect being at the same time the most normotensive and therefore caused the most
      beneficial effects. 

PMID- 24586809
TI  - The relationship between BMI and glycated albumin to glycated hemoglobin (GA/A1c)
      ratio according to glucose tolerance status.
AB  - Glycated albumin to glycated hemoglobin (GA/A1c) ratio is known to be inversely
      related with body mass index (BMI) and insulin secretory capacity. However, the
      reasons for this association remain unknown. We aimed to investigate whether BMI
      directly or indirectly influences GA/A1c by exerting effects on insulin secretion
      or resistance and to confirm whether these associations differ according to
      glucose tolerance status. We analyzed a total of 807 subjects [242 drug-naive
      type 2 diabetes (T2D), 378 prediabetes, and 187 normal glucose tolerance (NGT)].
      To assess the direct and indirect effects of BMI on GA/A1c ratio, structural
      equation modeling (SEM) was performed. GA/A1c ratio was set as a dependent
      variable, BMI was used as the independent variable, and homeostasis model
      assessment-pancreatic beta-cell function (HOMA-beta), homeostasis model
      assessment-insulin resistance (HOMA-IR), glucose level were used as mediator
      variables. The estimates of a direct effect of BMI on GA/A1c to be the strongest
      in NGT and weakest in T2D (-0.375 in NGT, -0.244 in prediabetes, and -0.189 in
      T2D). Conversely, the indirect effect of BMI on GA/A1c exerted through HOMA-beta
      and HOMA-IR was not statistically significant in NGT group, but significant in
      prediabetes and T2D groups (0.089 in prediabetes, -0.003 in T2D). It was found
      that HOMA-beta or HOMA-IR indirectly influences GA/A1c in T2D and prediabetes
      group through affecting fasting and postprandial glucose level. The relationship
      between GA/A1c and BMI is due to the direct effect of BMI on GA/A1c in NGT group,
      while in T2D and prediabetes groups, this association is mostly a result of BMI
      influencing blood glucose through insulin resistance or secretion. 

PMID- 24586810
TI  - Loss of the HPV-infection resistance EVER2 protein impairs NF-kappaB signaling
      pathways in keratinocytes.
AB  - Homozygous mutations in EVER genes cause epidermodysplasia verruciformis (EV),
      characterized by an immune defect and the development of skin cancers associated
      with beta-human papillomavirus (HPV) infections. The effects of EVER protein loss
      on the keratinocyte immune response remain unknown. We show here that EVER2 plays
      a critical role in the interplay between the NF-kappaB and JNK/AP-1 signaling
      pathways. EVER2-deficient cells overproduce IL-6 following the upregulation of
      JNK activation. They respond poorly to phorbol ester and TNF via the NF-kappaB
      pathway. They have lower levels of IKKalpha subunit, potentially accounting for
      impairments of p100 processing and the alternative NF-kappaB pathway. The loss of
      EVER2 is associated with an unusual TRAF protein profile. We demonstrate that
      EVER2 deficiency sustains TRAF2 ubiquitination and decreases the pool of TRAF2
      available in the detergent-soluble fraction of the cell. Finally, we demonstrate
      that EVER2 loss induces constitutive PKCalpha-dependent c-jun phosphorylation and
      facilitates activation of the HPV5 long control region through a JNK-dependent
      pathway. These findings indicate that defects of the EVER2 gene may create an
      environment conducive to HPV replication and the persistence of lesions with the
      potential to develop into skin cancer.

PMID- 24586811
TI  - The role of Carboxydothermus hydrogenoformans in the conversion of calcium
      phosphate from amorphous to crystalline state.
AB  - Two previously unknown modes of biomineralization observed in the presence of
      Carboxydothermus hydrogenoformans are presented. Following the addition of NaHCO3
      and the formation of an amorphous calcium phosphate precipitate in a DSMZ medium
      inoculated with C. hydrogenoformans, two distinct crystalline solids were
      recovered after 15 and 30 days of incubation. The first of these solids occurred
      as micrometric clusters of blocky, angular crystals, which were associated with
      bacterial biofilm. The second solid occurred as 30-50 nm nanorods that were found
      scattered among the organic products of bacterial lysis. The biphasic mixture of
      solids was clearly dominated by the first phase. The X-ray diffractometry (XRD)
      peaks and Fourier transform infrared spectroscopy (FTIR) spectrum of this
      biphasic material consistently showed features characteristic of Mg-whitlockite.
      No organic content or protein could be identified by dissolving the solids. In
      both cases, the mode of biomineralization appears to be biologically induced
      rather than biologically controlled. Since Mg is known to be a strong inhibitor
      of the nucleation and growth of CaP, C. hydrogenoformans may act by providing
      sites that chelate Mg or form complexes with it, thus decreasing its activity as
      nucleation and crystal growth inhibitor. The synthesis of whitlockite and nano
      HAP-like material by C. hydrogenoformans demonstrates the versatility of this
      organism also known for its ability to perform the water-gas shift reaction, and
      may have applications in bacterially mediated synthesis of CaP materials, as an
      environmentally friendly alternative process. 

PMID- 24586812
TI  - Transcriptomic profiling of differential responses to drought in two freshwater
      mussel species, the giant floater Pyganodon grandis and the pondhorn Uniomerus
      tetralasmus.
AB  - The southeastern US has experienced recurrent drought during recent decades.
      Increasing demand for water, as precipitation decreases, exacerbates stress on
      the aquatic biota of the Southeast: a global hotspot for freshwater mussel,
      crayfish, and fish diversity. Freshwater unionid mussels are ideal candidates to
      study linkages between ecophysiological and behavioral responses to drought.
      Previous work on co-occurring mussel species suggests a coupling of physiology
      and behavior along a gradient ranging from intolerant species such as Pyganodon
      grandis (giant floater) that track receding waters and rarely burrow in the
      substrates to tolerant species such as Uniomerus tetralasmus (pondhorn) that
      rarely track receding waters, but readily burrow into the drying sediments. We
      utilized a next-generation sequencing-based RNA-Seq approach to examine
      heat/desiccation-induced transcriptomic profiles of these two species in order to
      identify linkages between patterns of gene expression, physiology and behavior.
      Sequencing produced over 425 million 100 bp reads. Using the de novo assembly
      package Trinity, we assembled the short reads into 321,250 contigs from giant
      floater (average length 835 bp) and 385,735 contigs from pondhorn (average length
      929 bp). BLAST-based annotation and gene expression analysis revealed 2,832
      differentially expressed genes in giant floater and 2,758 differentially
      expressed genes in pondhorn. Trancriptomic responses included changes in
      molecular chaperones, oxidative stress profiles, cell cycling, energy metabolism,
      immunity, and cytoskeletal rearrangements. Comparative analyses between species
      indicated significantly higher induction of molecular chaperones and cytoskeletal
      elements in the intolerant P. grandis as well as important differences in genes
      regulating apoptosis and immunity. 

PMID- 24586813
TI  - Low socioeconomic status is associated with worse survival in children with
      cancer: a systematic review.
AB  - BACKGROUND: While low socioeconomic status (SES) has been associated with
      inferior cancer outcome among adults, its impact in pediatric oncology is
      unclear. Our objective was therefore to conduct a systematic review to determine
      the impact of SES upon outcome in children with cancer. METHODS: We searched Ovid
      Medline, EMBASE and CINAHL from inception to December 2012. Studies for which
      survival-related outcomes were reported by socioeconomic subgroups were eligible
      for inclusion. Two reviewers independently assessed articles and extracted data.
      Given anticipated heterogeneity, no quantitative meta-analyses were planned a
      priori. RESULTS: Of 7,737 publications, 527 in ten languages met criteria for
      full review; 36 studies met final inclusion criteria. In low- and middle-income
      countries (LMIC), lower SES was uniformly associated with inferior survival,
      regardless of the measure chosen. The majority of associations were statistically
      significant. Of 52 associations between socioeconomic variables and outcome among
      high-income country (HIC) children, 38 (73.1%) found low SES to be associated
      with worse survival, 15 of which were statistically significant. Of the remaining
      14 (no association or high SES associated with worse survival), only one was
      statistically significant. Both HIC studies examining the effect of insurance
      found uninsured status to be statistically associated with inferior survival.
      CONCLUSIONS: Socioeconomic gradients in which low SES is associated with inferior
      childhood cancer survival are ubiquitous in LMIC and common in HIC. Future
      studies should elucidate mechanisms underlying these gradients, allowing the
      design of interventions mediating socioeconomic effects. Targeting the effect of
      low SES will allow for further improvements in childhood cancer survival.

PMID- 24586814
TI  - The pentachlorophenol metabolite tetrachlorohydroquinone induces massive ROS and
      prolonged p-ERK expression in splenocytes, leading to inhibition of apoptosis and
      necrotic cell death.
AB  - Pentachlorophenol (PCP) has been used extensively as a biocide and a wood
      preservative and has been reported to be immunosuppressive in rodents and humans.
      Tetrachlorohydroquinone (TCHQ) is a major metabolite of PCP. TCHQ has been
      identified as the main cause of PCP-induced genotoxicity due to reactive oxidant
      stress (ROS). However, the precise mechanisms associated with the immunotoxic
      effects of PCP and TCHQ remain unclear. The aim of this study was to examine the
      effects of PCP and TCHQ on the induction of ROS and injury to primary mouse
      splenocytes. Our results shown that TCHQ was more toxic than PCP and that a high
      dose of TCHQ led to necrotic cell death of the splenocytes through induction of
      massive and sudden ROS and prolonged ROS-triggered ERK activation. Inhibition of
      ROS production by N-acetyl-cysteine (NAC) partially restored the mitochondrial
      membrane potential, inhibited ERK activity, elevated caspase-3 activity and PARP
      cleavage, and, eventually, switched the TCHQ-induced necrosis to apoptosis. We
      suggest that prolonged ERK activation is essential for TCHQ-induced necrosis, and
      that ROS play a pivotal role in the different TCHQ-induced cell death mechanisms.

PMID- 24586815
TI  - Ultrasound can detect macroscopically undetectable changes in osteoarthritis
      reflecting the superficial histological and biochemical degeneration: ex vivo
      study of rabbit and human cartilage.
AB  - Recognizing subtle cartilage changes in the preclinical stage of osteoarthritis
      (OA) is essential for early diagnosis. To this end, the ability of the ultrasound
      signal intensity to detect macroscopically undetectable cartilage change was
      investigated. In this study, cartilage of rabbit OA model and human OA samples
      was examined by macroscopic evaluation, ultrasound signal intensity, histology
      with Mankin scores, and Fourier transform infrared imaging (FTIRI) analysis.
      Rabbit OA was induced by anterior cruciate ligament transection and evaluated at
      1, 2, 4 and 12 weeks. Twenty human samples were harvested during total knee
      arthroplasty from OA patients who had macroscopically normal human cartilage
      (ICRS grade 0) on the lateral femoral condyle. In the animal study, there was no
      macroscopic OA change at 2 weeks, but histology detected degenerative changes at
      this time point. Ultrasound signal intensity also detected degeneration at 2
      weeks. In human samples, all samples were obtained from macroscopically intact
      site, however nearly normal (0 <= Mankin score <2), early OA (2 <= Mankin score
      <6), and moderate OA (6 <= Mankin score <10) samples were actually intermixed.
      Ultrasound signal intensity was significantly different among these 3 stages and
      was well correlated with Mankin scores (R = -0.80) and FTIR parameters related to
      collagen and proteoglycan content in superficial zone. In conclusion, ultrasound
      can detect microscopic cartilage deterioration when such changes do not exist
      macroscopically, reflecting superficial histological and biochemical changes.

PMID- 24586817
TI  - Motor cortex-periaqueductal gray-spinal cord neuronal circuitry may involve in
      modulation of nociception: a virally mediated transsynaptic tracing study in
      spinally transected transgenic mouse model.
AB  - Several studies have shown that motor cortex stimulation provided pain relief by
      motor cortex plasticity and activating descending inhibitory pain control
      systems. Recent evidence indicated that the melanocortin-4 receptor (MC4R) in the
      periaqueductal gray played an important role in neuropathic pain. This study was
      designed to assess whether MC4R signaling existed in motor cortex-periaqueductal
      gray-spinal cord neuronal circuitry modulated the activity of sympathetic pathway
      by a virally mediated transsynaptic tracing study. Pseudorabies virus (PRV)-614
      was injected into the left gastrocnemius muscle in adult male MC4R-green
      fluorescent protein (GFP) transgenic mice (n = 15). After a survival time of 4-6
      days, the mice (n = 5) were randomly assigned to humanely sacrifice, and spinal
      cords and brains were removed and sectioned, and processed for PRV-614
      visualization. Neurons involved in the efferent control of the left gastrocnemius
      muscle were identified following visualization of PRV-614 retrograde tracing. The
      neurochemical phenotype of MC4R-GFP-positive neurons was identified using
      fluorescence immunocytochemical labeling. PRV-614/MC4R-GFP dual labeled neurons
      were detected in spinal IML, periaqueductal gray and motor cortex. Our findings
      support the hypothesis that MC4R signaling in motor cortex-periaqueductal gray
      spinal cord neural pathway may participate in the modulation of the melanocortin
      sympathetic signaling and contribute to the descending modulation of nociceptive
      transmission, suggesting that MC4R signaling in motor cortex-periaqueductal gray
      spinal cord neural pathway may modulate the activity of sympathetic outflow
      sensitive to nociceptive signals.

PMID- 24586816
TI  - Oncogenic H-Ras up-regulates acid beta-hexosaminidase by a mechanism dependent on
      the autophagy regulator TFEB.
AB  - The expression of constitutively active H-RasV12 oncogene has been described to
      induce proliferative arrest and premature senescence in many cell models. There
      are a number of studies indicating an association between senescence and
      lysosomal enzyme alterations, e.g. lysosomal beta-galactosidase is the most
      widely used biomarker to detect senescence in cultured cells and we previously
      reported that H-RasV12 up-regulates lysosomal glycohydrolases enzymatic activity
      in human fibroblasts. Here we investigated the molecular mechanisms underlying
      lysosomal glycohydrolase beta-hexosaminidase up-regulation in human fibroblasts
      expressing the constitutively active H-RasV12. We demonstrated that H-Ras
      activation increases beta-hexosaminidase expression and secretion by a
      Raf/extracellular signal-regulated protein kinase dependent pathway, through a
      mechanism that relies on the activity of the transcription factor EB (TFEB).
      Because of the pivotal role of TFEB in the regulation of lysosomal system
      biogenesis and function, our results suggest that this could be a general
      mechanism to enhance lysosomal enzymes activity during oncogene-induced
      senescence. 

PMID- 24586818
TI  - Assembly of the novel five-component apicomplexan multi-aminoacyl-tRNA synthetase
      complex is driven by the hybrid scaffold protein Tg-p43.
AB  - In Toxoplasma gondii, as in other eukaryotes, a subset of the amino-acyl-tRNA
      synthetases are arranged into an abundant cytoplasmic multi-aminoacyl-tRNA
      synthetase (MARS) complex. Through a series of genetic pull-down assays, we have
      identified the enzymes of this complex as: methionyl-, glutaminyl-, glutamyl-,
      and tyrosyl-tRNA synthetases, and we show that the N-terminal GST-like domain of
      a partially disordered hybrid scaffold protein, Tg-p43, is sufficient for
      assembly of the intact complex. Our gel filtration studies revealed significant
      heterogeneity in the size and composition of isolated MARS complexes. By
      targeting the tyrosyl-tRNA synthetases subunit, which was found exclusively in
      the complete 1 MDa complex, we were able to directly visualize MARS particles in
      the electron microscope. Image analyses of the negative stain data revealed the
      observed heterogeneity and instability of these complexes to be driven by the
      intrinsic flexibility of the domain arrangements within the MARS complex. These
      studies provide unique insights into the assembly of these ubiquitous but poorly
      understood eukaryotic complexes. 

PMID- 24586819
TI  - Generation and characterisation of Friedreich ataxia YG8R mouse fibroblast and
      neural stem cell models.
AB  - BACKGROUND: Friedreich ataxia (FRDA) is an autosomal recessive neurodegenerative
      disease caused by GAA repeat expansion in the first intron of the FXN gene, which
      encodes frataxin, an essential mitochondrial protein. To further characterise the
      molecular abnormalities associated with FRDA pathogenesis and to hasten drug
      screening, the development and use of animal and cellular models is considered
      essential. Studies of lower organisms have already contributed to understanding
      FRDA disease pathology, but mammalian cells are more related to FRDA patient
      cells in physiological terms. METHODOLOGY/PRINCIPAL FINDINGS: We have generated
      fibroblast cells and neural stem cells (NSCs) from control Y47R mice (9 GAA
      repeats) and GAA repeat expansion YG8R mice (190+120 GAA repeats). We then
      differentiated the NSCs in to neurons, oligodendrocytes and astrocytes as
      confirmed by immunocytochemical analysis of cell specific markers. The three YG8R
      mouse cell types (fibroblasts, NSCs and differentiated NSCs) exhibit GAA repeat
      stability, together with reduced expression of frataxin and reduced aconitase
      activity compared to control Y47R cells. Furthermore, YG8R cells also show
      increased sensitivity to oxidative stress and downregulation of Pgc-1alpha and
      antioxidant gene expression levels, especially Sod2. We also analysed various DNA
      mismatch repair (MMR) gene expression levels and found that YG8R cells displayed
      significant reduction in expression of several MMR genes, which may contribute to
      the GAA repeat stability. CONCLUSIONS/SIGNIFICANCE: We describe the first
      fibroblast and NSC models from YG8R FRDA mice and we confirm that the NSCs can be
      differentiated into neurons and glia. These novel FRDA mouse cell models, which
      exhibit a FRDA-like cellular and molecular phenotype, will be valuable resources
      to further study FRDA molecular pathogenesis. They will also provide very useful
      tools for preclinical testing of frataxin-increasing compounds for FRDA drug
      therapy, for gene therapy, and as a source of cells for cell therapy testing in
      FRDA mice.

PMID- 24586820
TI  - Evidence for an epistatic effect between TP53 R72P and MDM2 T309G SNPs in HIV
      infection: a cross-sectional study in women from South Brazil.
AB  - OBJECTIVE: To investigate the associations of TP53 R72P and MDM2 T309G SNPs with
      HPV infection status, HPV oncogenic risk and HIV infection status. DESIGN: Cross
      sectional study combining two groups (150 HIV-negative and 100 HIV-positive) of
      women. METHODS: Data was collected using a closed questionnaire. DNA was
      extracted from cervical samples. HPV infection status was determined by nested
      PCR, and HPV oncogenic risk group by Sanger sequencing. Both SNPS were genotyped
      by PCR-RFLP. Crude and adjusted associations involving each exposure (R72P and
      T309G SNPs, as well as 13 models of epistasis) and each outcome (HPV status, HPV
      oncogenic risk group and HIV infection) were assessed using logistic regression.
      RESULTS: R72P SNP was protectively associated with HPV status (overdominant
      model), as well as T309G SNP with HPV oncogenic risk (strongest in the
      overdominant model). No epistatic model was associated with HPV status, but a
      dominant (R72P over T309G) protective epistatic effect was observed for HPV
      oncogenic risk. HIV status was strongly associated (risk factor) with different
      epistatic models, especially in models based on a visual inspection of the
      results. Moreover, HIV status was evidenced to be an effect mediator of the
      associations involving HPV oncogenic risk. CONCLUSIONS: We found evidence for a
      role of R72P and T309G SNPs in HPV status and HPV oncogenic risk (respectively),
      and strong associations were found for an epistatic effect in HIV status.
      Prospective studies in larger samples are warranted to validate our findings,
      which point to a novel role of these SNPs in HIV infection.

PMID- 24586821
TI  - Macrophage/epithelium cross-talk regulates cell cycle progression and migration
      in pancreatic progenitors.
AB  - Macrophages populate the mesenchymal compartment of all organs during
      embryogenesis and have been shown to support tissue organogenesis and
      regeneration by regulating remodeling of the extracellular microenvironment.
      Whether this mesenchymal component can also dictate select developmental
      decisions in epithelia is unknown. Here, using the embryonic pancreatic
      epithelium as model system, we show that macrophages drive the epithelium to
      execute two developmentally important choices, i.e. the exit from cell cycle and
      the acquisition of a migratory phenotype. We demonstrate that these developmental
      decisions are effectively imparted by macrophages activated toward an M2 fetal
      like functional state, and involve modulation of the adhesion receptor NCAM and
      an uncommon "paired-less" isoform of the transcription factor PAX6 in the
      epithelium. Over-expression of this PAX6 variant in pancreatic epithelia controls
      both cell motility and cell cycle progression in a gene-dosage dependent fashion.
      Importantly, induction of these phenotypes in embryonic pancreatic transplants by
      M2 macrophages in vivo is associated with an increased frequency of endocrine
      committed cells emerging from ductal progenitor pools. These results identify M2
      macrophages as key effectors capable of coordinating epithelial cell cycle
      withdrawal and cell migration, two events critical to pancreatic progenitors'
      delamination and progression toward their differentiated fates. 

PMID- 24586822
TI  - Altered spontaneous brain activity in primary open angle glaucoma: a resting
      state functional magnetic resonance imaging study.
AB  - BACKGROUND: Previous studies demonstrated that primary open angle glaucoma (POAG)
      is associated with abnormal brain structure; however, little is known about the
      changes in the local synchronization of spontaneous activity. The main objective
      of this study was to investigate spontaneous brain activity in patients with POAG
      using regional homogeneity (ReHo) analysis based on resting state functional
      magnetic resonance imaging (rs-fMRI). METHODOLOGY/PRINCIPAL FINDINGS: Thirty-nine
      POAG patients and forty-one age- and gender- matched healthy controls were
      finally included in the study. ReHo values were used to evaluate spontaneous
      brain activity and whole brain voxel-wise analysis of ReHo was carried out to
      detect differences by region in spontaneous brain activity between groups.
      Compared to controls, POAG patients showed increased ReHo in the right dorsal
      anterior cingulated cortex, the bilateral medial frontal gyrus and the right
      cerebellar anterior lobe, and decreased ReHo in the bilateral calcarine,
      bilateral precuneus gryus, bilateral pre/postcentral gyrus, left inferior
      parietal lobule and left cerebellum posterior lobe. A multiple linear regression
      analysis was performed to explore the relationships between clinical measures and
      ReHo by region showed significant group differences in the POAG group. Negative
      correlations were found between age and the ReHo values of the superior frontal
      gyrus (r = -0.323, p = 0.045), left calcarine (r = -0.357, p = 0.026) and
      inferior parietal lobule (r = -0.362, p = 0.024). A negative correlation was
      found between the ReHo values of the left precuneus and the cumulative mean
      defect (r = -0.400, p = 0.012). CONCLUSIONS: POAG was associated with abnormal
      brain spontaneous activity in some brain regions and such changed regional
      activity may be associated with clinical parameters. Spontaneous brain activity
      may play a role in POAG initiation and progression.

PMID- 24586823
TI  - Value learning and arousal in the extinction of probabilistic rewards: the role
      of dopamine in a modified temporal difference model.
AB  - Because most rewarding events are probabilistic and changing, the extinction of
      probabilistic rewards is important for survival. It has been proposed that the
      extinction of probabilistic rewards depends on arousal and the amount of learning
      of reward values. Midbrain dopamine neurons were suggested to play a role in both
      arousal and learning reward values. Despite extensive research on modeling
      dopaminergic activity in reward learning (e.g. temporal difference models), few
      studies have been done on modeling its role in arousal. Although temporal
      difference models capture key characteristics of dopaminergic activity during the
      extinction of deterministic rewards, they have been less successful at simulating
      the extinction of probabilistic rewards. By adding an arousal signal to a
      temporal difference model, we were able to simulate the extinction of
      probabilistic rewards and its dependence on the amount of learning. Our
      simulations propose that arousal allows the probability of reward to have lasting
      effects on the updating of reward value, which slows the extinction of low
      probability rewards. Using this model, we predicted that, by signaling the
      prediction error, dopamine determines the learned reward value that has to be
      extinguished during extinction and participates in regulating the size of the
      arousal signal that controls the learning rate. These predictions were supported
      by pharmacological experiments in rats. 

PMID- 24586824
TI  - Transcriptome analysis reveals common and distinct mechanisms for sheepgrass
      (Leymus chinensis) responses to defoliation compared to mechanical wounding.
AB  - BACKGROUND: Herbivore grazing is a multiple-component process that includes
      wounding, defoliation, and saliva deposition. Despite the extensive published
      research on mechanical wounding and defoliation, no analysis to identify the
      genes that specify defoliation and mechanical wounding has been performed.
      Moreover, the influence of the expression of these genes on plant regrowth after
      defoliation remains poorly understood. RESULTS: Seven cDNA libraries for RNA
      samples collected from stubble tissues that had been mechanically wounded or
      defoliated at 2, 6 and 24 h along with the control were sequenced using the
      Illumina/Solexa platform. A comparative transcriptomic analysis of the sequencing
      data was conducted. In total, 1,836 and 3,238 genes were detected with
      significant differential expression levels after wounding and defoliation,
      respectively, during one day. GO, KOG and pathway-based enrichment analyses were
      performed to determine and further understand the biological functions of those
      differentially expressed genes (DEGs). The results demonstrated that both
      wounding and defoliation activated the systemic synthesis of jasmonate (JA).
      However, defoliation specifically reduced the expression levels of ribosomal
      protein genes, cell division or cell expansion-related genes, and lignin
      biosynthesis genes and may have negatively affected plant growth. Further
      analysis revealed that the regrowth of elongating leaves was significantly
      retarded after defoliation at 6 h through the following 7 days of measurement,
      suggesting that the gene expression pattern and phenotype are consistent. Fifteen
      genes were selected, and their expression levels were confirmed by quantitative
      RT-PCR (qRT-PCR). Thirteen of them exhibited expression patterns consistent with
      the digital gene expression (DGE) data. CONCLUSIONS: These sequencing datasets
      allowed us to elucidate the common and distinct mechanisms of plant responses to
      defoliation and wounding. Additionally, the distinct DEGs represent a valuable
      resource for novel gene discovery that may improve plant resistance to
      defoliation from various processes.

PMID- 24586825
TI  - High detection rates of enteropathogens in asymptomatic children attending day
      care.
AB  - BACKGROUND: Gastroenteritis morbidity is high among children under the age of
      four, especially amongst those who attend day care. OBJECTIVE: To determine the
      prevalence of a range of enteropathogens in the intestinal flora of children
      attending day care and to relate their occurrence with characteristics of the
      sampled child and the sampling season. METHODS: We performed three years of
      enteropathogen surveillance in a network of 29 child day care centers in the
      Netherlands. The centers were instructed to take one fecal sample from ten
      randomly chosen children each month, regardless of gastrointestinal symptoms at
      time of sampling. All samples were analyzed for the molecular detection of 16
      enteropathogenic bacteria, parasites and viruses by real-time multiplex PCR.
      RESULTS: Enteropathogens were detected in 78.0% of the 5197 fecal samples. Of the
      total, 95.4% of samples were obtained from children who had no gastroenteritis
      symptoms at time of sampling. Bacterial enteropathogens were detected most often
      (most prevalent EPEC, 19.9%), followed by parasitic enteropathogens (most
      prevalent: D. fragilis, 22.1%) and viral enteropathogens (most prevalent:
      norovirus, 9.5%). 4.6% of samples related to children that experienced symptoms
      of gastroenteritis at time of sampling. Only rotavirus and norovirus were
      significantly associated with gastroenteritis among day care attendees.
      CONCLUSIONS: Our study indicates that asymptomatic infections with
      enteropathogens in day care attendees are not a rare event and that
      gastroenteritis caused by infections with these enteropathogens is only one
      expression of their presence.

PMID- 24586827
TI  - Meta-analysis of pollen limitation reveals the relevance of pollination
      generalization in the Atlantic forest of Brazil.
AB  - Despite the extensive knowledge of pollen limitation in angiosperms, its
      assessment within tropical forests is still limited. Especially lacking are large
      scale comparisons of species within this biome - one that is highly diverse but
      also becoming increasingly threatened. In fact, many tropical plant species
      depend upon pollinators for reproduction but evaluation of the impact of this
      dependence via different levels of pollination specialization has yet to be made
      at the biome scale. We assessed the occurrence and magnitude of pollen limitation
      for species in the Brazilian Atlantic forest and tested the association of
      pollination specialization, breeding system, and life habit with pollination
      efficiency. We compiled data from studies published between 1985 and 2012. We
      calculated species' effect size (d) from data on fruit set after hand cross
      pollination and natural pollination and conducted standard and phylogenetically
      independent meta-analysis. Overall pollen limitation was moderate, with magnitude
      of 0.50, and 95% confidence interval [0.37, 0.62] for 126 species. Pollen
      limitation was observed in 39% of species. Pollination specialization was the
      factor that best explained the occurrence of pollen limitation. Specifically,
      phenotypic and ecological specialists (plants with zygomorphic flowers and
      pollinated by one species of pollinator, respectively) had higher pollen
      limitation than generalist plants (actinomorphic flowers and pollination by two
      or more species). Functional generalists (plants pollinated by three or more
      functional groups) were not pollen limited. On the other hand, breeding system
      and life habit were not associated to pollen limitation. Pollen limitation was
      observed in the Atlantic forest and its magnitude was comparable to that for
      angiosperms as a whole. The finding that pollination specialization was the
      strongest predictor of pollen limitation suggests that specialist plants in this
      biome may be most prone to the reproductive failure as a result of pollinator
      loss. 

PMID- 24586826
TI  - Neutrophil gelatinase-associated lipocalin increases HLA-G(+)/FoxP3(+) T
      regulatory cell population in an in vitro model of PBMC.
AB  - BACKGROUND: Neutrophil gelatinase-associated lipocalin (NGAL) is emerging as a
      mediator of various biological and pathological states. However, the specific
      biological role of this molecule remains unclear, as it serves as a biomarker for
      many conditions. The high sensitivity of NGAL as a biomarker coupled with
      relatively low specificity may hide important biological roles. Data point toward
      an acute compensatory, protective role for NGAL in response to adverse cellular
      stresses, including inflammatory and oxidative stress. The aim of this study was
      to understand whether NGAL modulates the T-cell response through regulation of
      the human leukocyte antigen G (HLA-G) complex, which is a mediator of tolerance.
      METHODOLOGY/PRINCIPAL FINDINGS: Peripheral blood mononuclear cells (PBMCs) were
      obtained from eight healthy donors and isolated by centrifugation on a Ficoll
      gradient. All donors gave informed consent. PBMCs were treated with four
      different concentrations of NGAL (40-320 ng/ml) in an iron-loaded or iron-free
      form. Changes in cell phenotype were analyzed by flow cytometry. NGAL stimulated
      expression of HLA-G on CD4+ T cells in a dose- and iron-dependent manner. Iron
      deficiency prevented NGAL-mediated effects, such that HLA-G expression was
      unaltered. Furthermore, NGAL treatment affected stimulation of regulatory T cells
      and in vitro expansion of CD4(+) CD25(+) FoxP3(+) cells. An NGAL neutralizing
      antibody limited HLA-G expression and significantly decreased the percentage of
      CD4(+) CD25(+) FoxP3(+) cells. CONCLUSIONS/SIGNIFICANCE: We provide in vitro
      evidence that NGAL is involved in cellular immunity. The potential role of NGAL
      as an immunomodulatory molecule is based on its ability to induce immune
      tolerance by upregulating HLA-G expression and expansion of T-regulatory cells in
      healthy donors. Future studies should further evaluate the role of NGAL in
      immunology and immunomodulation and its possible relationship to
      immunosuppressive therapy efficacy, tolerance induction in transplant patients,
      and other immunological disorders.

PMID- 24586828
TI  - QTL mapping in eggplant reveals clusters of yield-related loci and orthology with
      the tomato genome.
AB  - In spite of its widespread cultivation and nutritional and economic importance,
      the eggplant (Solanum melongena L.) genome has not been extensively explored. A
      lack of knowledge of the patterns of inheritance of key agronomic traits has
      hindered the exploitation of marker technologies to accelerate its genetic
      improvement. An already established F2 intraspecific population of eggplant bred
      from the cross '305E40' x '67/3' was phenotyped for 20 agronomically relevant
      traits at two sites. Up to seven quantitative trait loci (QTL) per trait were
      identified and the percentage of the phenotypic variance (PV) explained per QTL
      ranged from 4 to 93%. Not all the QTL were detectable at both sites, but for each
      trait at least one major QTL (PV explained >= 10%) was identified. Although no
      detectable QTL x environment interaction was found, some QTL identified were
      location-specific. Many of the fruit-related QTL clustered within specific
      chromosomal regions, reflecting either linkage and/or pleiotropy. Evidence for
      putative tomato orthologous QTL/genes was obtained for several of the eggplant
      QTL. Information regarding the inheritance of key agronomic traits was obtained.
      Some of the QTL, along with their respective linked markers, may be useful in the
      context of marker-assisted breeding.

PMID- 24586829
TI  - Real-time in vivo imaging of butterfly wing development: revealing the cellular
      dynamics of the pupal wing tissue.
AB  - Butterfly wings are covered with regularly arranged single-colored scales that
      are formed at the pupal stage. Understanding pupal wing development is therefore
      crucial to understand wing color pattern formation. Here, we successfully
      employed real-time in vivo imaging techniques to observe pupal hindwing
      development over time in the blue pansy butterfly, Junonia orithya. A transparent
      sheet of epithelial cells that were not yet regularly arranged was observed
      immediately after pupation. Bright-field imaging and autofluorescent imaging
      revealed free-moving hemocytes and tracheal branches of a crinoid-like structure
      underneath the epithelium. The wing tissue gradually became gray-white,
      epithelial cells were arranged regularly, and hemocytes disappeared, except in
      the bordering lacuna, after which scales grew. The dynamics of the epithelial
      cells and scale growth were also confirmed by fluorescent imaging. Fluorescent in
      vivo staining further revealed that these cells harbored many mitochondria at the
      surface of the epithelium. Organizing centers for the border symmetry system were
      apparent immediately after pupation, exhibiting a relatively dark optical
      character following treatment with fluorescent dyes, as well as in
      autofluorescent images. The wing tissue exhibited slow and low-frequency
      contraction pulses with a cycle of approximately 10 to 20 minutes, mainly
      occurring at 2 to 3 days postpupation. The pulses gradually became slower and
      weaker and eventually stopped. The wing tissue area became larger after
      contraction, which also coincided with an increase in the autofluorescence
      intensity that might have been caused by scale growth. Examination of the pattern
      of color development revealed that the black pigment was first deposited in
      patches in the central areas of an eyespot black ring and a parafocal element.
      These results of live in vivo imaging that covered wide wing area for a long time
      can serve as a foundation for studying the cellular dynamics of living wing
      tissues in butterflies. 

PMID- 24586831
TI  - Micronutrient intakes among women of reproductive age in Vietnam.
AB  - BACKGROUND: Micronutrient deficiencies are a public health concern worldwide
      negatively affecting maternal and child health outcomes. The primary underlying
      causes of micronutrient deficiencies are insufficient intake and poor
      bioavailability of micronutrients. However, reliable data on micronutrient
      intakes are sparse. The objectives of this study were to identify the key local
      food sources providing the majority of micronutrients and assess the adequacy and
      determinants of micronutrient intakes. METHODS: The study used data from a survey
      of 4,983 rural women of reproductive age (WRA) participating in a preconception
      micronutrient supplementation trial in Vietnam. Micronutrient intakes were
      assessed using a validated 107-item semi-quantitative food-frequency
      questionnaire. Multivariate linear and logistic regression analyses were used to
      examine the association between socioeconomic status and micronutrient intakes.
      RESULTS: Starchy staples were the main source of iron and zinc (37% and 54%,
      respectively) with only a small proportion from meat (10% and 18%, respectively).
      The primary source of folate and vitamin A were vegetables; vitamin B12 came from
      meat and eggs. The proportion of the population with intakes below the estimated
      average requirement was 25% for iron, 16% for zinc, 54% for folate, 64% for
      vitamin B12 and 27% for vitamin A. Socioeconomic status was the main determinant
      of micronutrient intakes. WRA in the highest quintile consumed 26% more iron, 19%
      more zinc, 36% more folate, 82% more vitamin B12 and 47% more vitamin A compared
      to those in the lowest quintile. Women in the upper quintiles of SES were more
      likely to obtain nutrients from more nutritious and higher bioavailable foods
      than those in the lowest quintile. CONCLUSIONS: Underprivileged women were at
      increased risk for insufficient micronutrient intakes due to poor diet quality.
      Targeted efforts to promote the consumption of local nutrient rich foods along
      with educational programs and social development are needed.

PMID- 24586830
TI  - Dynamic visualization of dendritic cell-antigen interactions in the skin
      following transcutaneous immunization.
AB  - Delivery of vaccines into the skin provides many advantages over traditional
      parenteral vaccination and is a promising approach due to the abundance of
      antigen presenting cells (APC) residing in the skin including Langerhans cells
      (LC) and dermal dendritic cells (DDC). However, the main obstacle for
      transcutaneous immunization (TCI) is the effective delivery of the vaccine
      through the stratum corneum (SC) barrier to the APC in the deeper skin layers.
      This study therefore utilized microneedles (MN) and a lipid-based colloidal
      delivery system (cubosomes) as a synergistic approach for the delivery of
      vaccines to APC in the skin. The process of vaccine uptake and recruitment by
      specific types of skin APC was investigated in real-time over 4 hours in B6.Cg-Tg
      (Itgax-EYFP) 1 Mnz/J mice by two-photon microscopy. Incorporation of the vaccine
      into a particulate delivery system and the use of MN preferentially increased
      vaccine antigen uptake by a highly motile subpopulation of skin APC known as
      CD207+ DC. No uptake of antigen or any response to immunisation by LC could be
      detected.

PMID- 24586833
TI  - Diagnosis of canine leptospirosis by a highly sensitive FRET-PCR targeting the
      lig genes.
AB  - Canine leptospirosis is underdiagnosed due to its wide spectrum of clinical
      presentations and the lack of a rapid and sensitive test for the accurate
      diagnosis of acute and chronic infections. In this study, we developed a highly
      sensitive and specific fluorescence resonance energy transfer (FRET)-PCR to
      detect common pathogenic leptospires in dogs, including Leptospira interrogans
      serovars Autumnalis, Canicola, Copenhageni (Icterohaemorrhagiae serogroup) and
      Pomona, and Leptospira kirschneri serovar Grippotyphosa. This PCR targets the lig
      genes, exclusively found in the pathogenic Leptospira species but not in
      saprophytic species (L. biflexa). A robust, high-stringency step-down real-time
      platform was coupled to the highly specific detection of leptospiral DNA by
      fluorescently labeled FRET probes. This enabled the detection of a single copy of
      the lig gene in a PCR containing DNA from up to 50 uL canine blood or 400 uL
      urine. Sensitivity determination by use of limiting serial dilutions of extracted
      leptospiral DNA indicated that the lig FRET-PCR we established was almost 100
      fold more sensitive than the widely accepted lipL32 SYBR assay and 10-fold more
      sensitive than a 16S rRNA TaqMan assay. Application of this method to 207 dogs
      with potential leptospiral infection enabled us to diagnose three cases of canine
      leptospirosis characterized by low amounts of leptospiral DNA in body fluids.
      Detection of canine leptospirosis with the lig FRET-PCR was more sensitive with
      the lig FRET-PCR than with the 16S rRNA TaqMan PCR, which detected only 2 of the
      3 cases, and the lipL32 SYBR PCR, which detected none of the 3 dogs with
      leptospirosis. 

PMID- 24586832
TI  - Sentrin/SUMO specific proteases as novel tissue-selective modulators of vitamin D
      receptor-mediated signaling.
AB  - Vitamin D receptor (VDR) is a substrate for modification with small ubiquitin
      like modifier (SUMO). To further assess the role of reversible SUMOylation within
      the vitamin D hormonal response, we evaluated the effects of sentrin/SUMO
      specific proteases (SENPs) that can function to remove small ubiquitin-like
      modifier (SUMO) from target proteins upon the activities of VDR and related
      receptors. We report that SENP1 and SENP2 strikingly potentiate ligand-mediated
      transactivation of VDR and also its heterodimeric partner, retinoid X receptor
      (RXRalpha) with depletion of cellular SENP1 significantly diminishing the
      hormonal responsiveness of the endogenous vitamin D target gene CYP24A1. We find
      that SENP-directed modulation of VDR activity is cell line-dependent, achieving
      potent modulatory effects in Caco-2 and HEK-293 cells, while in MCF-7 cells the
      vitamin D signal is unaffected by any tested SENP. In support of their function
      as novel modulators of the vitamin D hormonal pathway we demonstrate that both
      SENP1 and SENP2 can interact with VDR and reverse its modification with SUMO2. In
      a preliminary analysis we identify lysine 91, a residue known to be critical for
      formation and DNA binding of the VDR-RXR heterodimer, as a minor SUMO acceptor
      site within VDR. In combination, our results support a repressor function for
      SUMOylation of VDR and reveal SENPs as a novel class of VDR/RXR co-regulatory
      protein that significantly modulate the vitamin D response and which could also
      have important impact upon the functionality of both RXR-containing homo and
      heterodimers. 

PMID- 24586834
TI  - Assessing interactions of two loci (rs4242382 and rs10486567) in familial
      prostate cancer: statistical evaluation of epistasis.
AB  - Understanding the impact of multiple genetic variants and their interactions on
      the disease penetrance of familial multiple prostate cancer is very relevant to
      the overall understanding of carcinogenesis. We assessed the joint effect of two
      loci on rs4242382 at 8q24 and rs10486567 at 7p15.2 to this end. We analyzed the
      data from a Finnish family-based genetic study, which was composed of 947 men
      including 228 cases in 75 families, to evaluate the respective effects of the two
      loci on the disease penetrance; in particular, the occurrence and number of
      prostate cancer cases within a family were utilized to evaluate the interactions
      between the two loci under the additive and multiplicative Poisson regression
      models. The risk alleles A at rs4242382 (OR = 1.14, 95% CI 1.08-1.19, P<0.0001)
      and a risk allele A at rs10486567 (OR = 1.06, 96%CI 1.01-1.11, P = 0.0208) were
      found to be associated with an increased risk of familial PrCa, especially with
      four or more cases within a family. A multiplicative model fitted the joint
      effect better than an additive model (likelihood ratio test X(2) = 13.89,
      P<0.0001). The influence of the risk allele A at rs10486567 was higher in the
      presence of the risk allele A at rs4242382 (OR = 1.09 (1.01-1.18) vs. 1.01 (0.95
      1.07)). Similar findings were observed in non-aggressive PrCa, but not in
      aggressive PrCa. We demonstrated that two loci (rs4242382 and rs10486567) are
      highly associated with familial multiple PrCa, and the gene-gene interaction or
      statistical epistasis was consistent with the Fisher's multiplicative model.
      These loci's association and epistasis were observed for non-aggressive but not
      for aggressive tumors. The proposed statistical model can be further developed to
      accommodate multi-loci interactions to provide further insights into epistasis.

PMID- 24586835
TI  - Time since immigration and ethnicity as predictors of physical activity among
      Canadian youth: a cross-sectional study.
AB  - BACKGROUND: Little is known about patterns of physical activity engaged in by
      youth after they immigrate to a new country. This study aims to investigate
      relationships between immigrant generation and ethnicity with physical activity,
      and to determine if the relationship between immigrant generation and physical
      activity was modified by ethnicity. METHODS: The data sources were Cycle 6 (2009
      2010) of the Canadian Health Behaviour in School-Aged Children Study and the 2006
      Canada Census of Population. Participants (weighted n = 23,124) were young people
      from grades 6-10 in 436 schools. Students were asked where they were born, how
      long ago they moved to Canada, their ethnicity, and how many days a week they
      accumulated at least 60 minutes of moderate-to-vigorous physical activity (MVPA).
      RESULTS: Youth born outside of Canada were less likely to be active than peers
      born in Canada; 11% vs 15% reported 7 days/week of at least 60 minutes of MVPA (p
      = .001). MVPA increased with time since immigration. Compared to Canadian-born
      youth, youth who immigrated within the last 1-2 years were less likely to get
      sufficient MVPA on 4-6 days/week (odds ratio: 0.66, 95% confidence interval: 0.53
      0.82) and 7 days/week (0.62; 0.43-0.89). East and South-East Asian youth were
      less active, regardless of time since immigration: 4-6 days/week (0.67; 0.58
      0.79) and 7 days/week (0.37; 0.29-0.48). CONCLUSION: Time since immigration and
      ethnicity were associated with MVPA among Canadian youth. Mechanisms by which
      these differences occur need to be uncovered in order to identify barriers to
      physical activity participation among youth.

PMID- 24586836
TI  - Progress on the maternal mortality ratio reduction in Wuhan, China in 2001-2012.
AB  - BACKGROUND: Most maternal deaths occur in developing countries and most maternal
      deaths are avoidable. China has made a great effort to reduce MMR by three
      quarters to meet the fifth Millennium Development Goal (MDG5). METHODS: This
      retrospective study reviewed and analyzed maternal death data in Wuhan from 2001
      to 2012. Joinpoint regression and multivariate Poisson regression was conducted
      using the log-linear model to measure the association of the number of maternal
      deaths with time, cause of death, where the death occurred, and cognitive factors
      including knowledge, attitude, resource, and management stratified. RESULTS: The
      MMR declined from 33.41 per 100,000 live births in 2001 to 10.63 per 100,000 live
      births in 2012, with a total decline of 68.18% and an average annual decline of
      9.89%. From 2001-2012, the four major causes of maternal death were obstetric
      hemorrhage (35.16%), pregnancy complications (28.57%), amniotic fluid embolism
      (16.48%) and gestational hypertension (8.79%). Multivariate Poisson regression
      showed on average the MMR decreased by.17% each year from 2001-2006 and stayed
      stagnant since 2007-2012. CONCLUSIONS: With the reduction in MMR in obstetric
      death (e.g. obstetric hemorrhage), there had been a remarkable reduction in MMR
      in Wuhan in 2001-2012, which may be due to (1) the improvement in the obstetric
      quality of perinatal care service on prevention and treatment of obstetric
      hemorrhage and emergency care skills, and (2) the improvement in the maternal
      health management and quality of prenatal care. Interventions to further reduce
      the MMR include several efforts such as the following: (1) designing community
      based interventions, (2) providing subsidies to rural women and/hospitals for
      hospital delivery, (3) screening for pregnancy complications, and (4)
      establishing an emergency rescue system for critically ill pregnant women.

PMID- 24586837
TI  - Effect of radiographic contrast media on the spectrin/band3-network of the
      membrane skeleton of erythrocytes.
AB  - The membrane of red blood cells consists of a phospholipid bilayer with embedded
      membrane proteins and is associated on the cytoplasmatic side with a network of
      proteins, the membrane skeleton. Band3 has an important role as centre of the
      functional complexes e.g. gas exchange complex and as element of attachment for
      the membrane skeleton maintaining membrane stability and flexibility. Up to now
      it is unclear if band3 is involved in the morphology change of red blood cells
      after contact with radiographic contrast media. The study revealed for the first
      time that Iopromide induced markedly more severe alterations of the membrane
      skeleton compared to Iodixanol whose effects were similar to erythrocytes
      suspended in autologous plasma. A remarkable clustering of band3 was found
      associated with an accumulation of band3 in spicules and also a sequestration of
      band3 to the extracellular space. This was evidently accompanied by a gross
      reduction of functional band3 complexes combined with a dissociation of spectrin
      from band3 leading to a loss of homogeneity of the spectrin network. It could be
      demonstrated for the first time that RCM not only induced echinocyte formation
      but also exocytosis of particles at least coated with band3. 

PMID- 24586838
TI  - Association between socioeconomic factors and cancer risk: a population cohort
      study in Scotland (1991-2006).
AB  - BACKGROUND: Lung and upper aero-digestive tract (UADT) cancer risk are associated
      with low socioeconomic circumstances and routinely measured using area
      socioeconomic indices. We investigated effect of country of birth, marital
      status, one area deprivation measure and individual socioeconomic variables
      (economic activity, education, occupational social class, car ownership,
      household tenure) on risk associated with lung, UADT and all cancer combined
      (excluding non melanoma skin cancer). METHODS: We linked Scottish Longitudinal
      Study and Scottish Cancer Registry to follow 203,658 cohort members aged 15+
      years from 1991-2006. Relative risks (RR) were calculated using Poisson
      regression models by sex offset for person-years of follow-up. RESULTS: 21,832
      first primary tumours (including 3,505 lung, 1,206 UADT) were diagnosed.
      Regardless of cancer, economically inactivity (versus activity) was associated
      with increased risk (male: RR 1.14, 95% CI 1.10-1.18; female: RR 1.06, 95% CI
      1.02-1.11). For lung cancer, area deprivation remained significant after full
      adjustment suggesting the area deprivation cannot be fully explained by
      individual variables. No or non degree qualification (versus degree) was
      associated with increased lung risk; likewise for UADT risk (females only).
      Occupational social class associations were most pronounced and elevated for UADT
      risk. No car access (versus ownership) was associated with increased risk
      (excluding all cancer risk, males). Renting (versus home ownership) was
      associated with increased lung cancer risk, UADT cancer risk (males only) and all
      cancer risk (females only). Regardless of cancer group, elevated risk was
      associated with no education and living in deprived areas. CONCLUSIONS: Different
      and independent socioeconomic variables are inversely associated with different
      cancer risks in both sexes; no one socioeconomic variable captures all aspects of
      socioeconomic circumstances or life course. Association of multiple socioeconomic
      variables is likely to reflect the complexity and multifaceted nature of
      deprivation as well as the various roles of these dimensions over the life
      course.

PMID- 24586839
TI  - Physiological and molecular responses to variation of light intensity in rubber
      Tree (Hevea brasiliensis Muell. Arg.).
AB  - Light is one of most important factors to plants because it is necessary for
      photosynthesis. In this study, physiological and gene expression analyses under
      different light intensities were performed in the seedlings of rubber tree (Hevea
      brasiliensis) clone GT1. When light intensity increased from 20 to 1000 umol m(
      2) s(-1), there was no effect on the maximal quantum yield of photosystem II
      (PSII) photochemistry (Fv/Fm), indicating that high light intensity did not
      damage the structure and function of PSII reaction center. However, the effective
      photochemical quantum yield of PSII (Y(II)), photochemical quenching coefficient
      (qP), electron transfer rate (ETR), and coefficient of photochemical fluorescence
      quenching assuming interconnected PSII antennae (qL) were increased significantly
      as the light intensity increased, reached a maximum at 200 umol m(-2) s(-1), but
      decreased from 400 umol m(-2) s(-1). These results suggested that the PSII
      photochemistry showed an optimum performance at 200 umol m(-2) s(-1) light
      intensity. The chlorophyll content was increased along with the increase of light
      intensity when it was no more than 400 umol m(-2) s(-1). Since increasing light
      intensity caused significant increase in H2O2 content and decreases in the per
      unit activity of antioxidant enzymes SOD and POD, but the malondialdehyde (MDA)
      content was preserved at a low level even under high light intensity of 1000 umol
      m(-2) s(-1), suggesting that high light irradiation did not induce membrane lipid
      peroxidation in rubber tree. Moreover, expressions of antioxidant-related genes
      were significantly up-regulated with the increase of light intensity. They
      reached the maximum expression at 400 umol m(-2) s(-1), but decreased at 1000
      umol m(-2) s(-1). In conclusion, rubber tree could endure strong light
      irradiation via a specific mechanism. Adaptation to high light intensity is a
      complex process by regulating antioxidant enzymes activities, chloroplast
      formation, and related genes expressions in rubber tree. 

PMID- 24586840
TI  - V3-independent competitive resistance of a dual-X4 HIV-1 to the CXCR4 inhibitor
      AMD3100.
AB  - A CXCR4 inhibitor-resistant HIV-1 was isolated from a dual-X4 HIV-1 in vitro. The
      resistant variant displayed competitive resistance to the CXCR4 inhibitor
      AMD3100, indicating that the resistant variant had a higher affinity for CXCR4
      than that of the wild-type HIV-1. Amino acid sequence analyses revealed that the
      resistant variant harbored amino acid substitutions in the V2, C2, and C4
      regions, but no remarkable changes in the V3 loop. Site-directed mutagenesis
      confirmed that the changes in the C2 and C4 regions were principally involved in
      the reduced sensitivity to AMD3100. Furthermore, the change in the C4 region was
      associated with increased sensitivity to soluble CD4, and profoundly enhanced the
      entry efficiency of the virus. Therefore, it is likely that the resistant variant
      acquired the higher affinity for CD4/CXCR4 by the changes in non-V3 regions.
      Taken together, a CXCR4 inhibitor-resistant HIV-1 can evolve using a non-V3
      pathway. 

PMID- 24586841
TI  - Cilostazol add-on therapy in patients with mild dementia receiving donepezil: a
      retrospective study.
AB  - GOAL: Combinatorial therapy directed at both vascular and neurodegenerative
      aspects of dementia may offer a promising strategy for treatment of dementia,
      which often has a multifactorial basis in the elderly. We investigated whether
      the phosphodiesterase III inhibitor cilostazol, which is often used in the
      prevention of stroke and peripheral artery disease, may delay cognitive decline
      in the elderly receiving donepezil. METHODS: Medical records were retrospectively
      surveyed to identify patients who had received donepezil for more than one year
      and had undergone Mini-Mental State Examination (MMSE) at least at two time
      points. Those with an initial MMSE score of less than 27 points were subjected to
      analysis (n = 156), with a cut-point of 21/22 applied to assign them to mild (n =
      70) and moderate/severe (n = 86) dementia. The change of total MMSE score per
      year was compared between patients who had received donepezil and those given
      both donepezil and cilostazol. FINDINGS: In patients with mild dementia who had
      received donepezil and cilostazol (n = 34; 77.2+/-6.8 years old), the annual
      change in MMSE score was -0.5+/-1.6 during an observational period of 28.6+/-11.7
      months, with those receiving donepezil only (n = 36; 78.4+/-6.5 years old)
      scoring less (-2.2+/-4.1) during 30.4+/-12.8 months with a statistical intergroup
      difference (p = 0.022). Multivariate analysis showed that absence of cilostazol
      treatment was the only significant predictor of MMSE decline. A positive effect
      of cilostazol was found in three subscale scores of MMSE, orientation for time or
      place and delayed recall. By clear contrast, in patients with moderate/severe
      dementia, there were no intergroup differences in decrease of total or subscale
      MMSE scores between the two groups. CONCLUSIONS: These results suggest potential
      for cilostazol treatment in the suppression of cognitive decline in patients
      receiving donepezil with mild dementia but not in those with moderate/severe
      dementia.

PMID- 24586842
TI  - Clinical validation of a PCR assay for the detection of EGFR mutations in non
      small-cell lung cancer: retrospective testing of specimens from the EURTAC trial.
AB  - The EURTAC trial demonstrated that the tyrosine kinase inhibitor (TKI) erlotinib
      was superior to chemotherapy as first-line therapy for advanced non-small cell
      lung cancers (NSCLC) that harbor EGFR activating mutations in a predominantly
      Caucasian population. Based on EURTAC and several Asian trials, anti-EGFR TKIs
      are standard of care for EGFR mutation-positive NSCLC. We sought to validate a
      rapid multiplex EGFR mutation assay as a companion diagnostic assay to select
      patients for this therapy. Samples from the EURTAC trial were prospectively
      screened for EGFR mutations using a combination of laboratory-developed tests
      (LDTs), and tested retrospectively with the cobas EGFR mutation test (EGFR PCR
      test). The EGFR PCR test results were compared to the original LDT results and to
      Sanger sequencing, using a subset of specimens from patients screened for the
      trial. Residual tissue was available from 487 (47%) of the 1044 patients screened
      for the trial. The EGFR PCR test showed high concordance with LDT results with a
      96.3% overall agreement. The clinical outcome of patients who were EGFR-mutation
      detected by the EGFR PCR test was very similar to the entire EURTAC cohort. The
      concordance between the EGFR PCR test and Sanger sequencing was 90.6%. In 78.9%
      of the discordant samples, the EGFR PCR test result was confirmed by a sensitive
      deep sequencing assay. This retrospective study demonstrates the clinical utility
      of the EGFR PCR test in the accurate selection of patients for anti-EGFR TKI
      therapy. The EGFR PCR test demonstrated improved performance relative to Sanger
      sequencing. 

PMID- 24586843
TI  - Variation in the helical structure of native collagen.
AB  - The structure of collagen has been a matter of curiosity, investigation, and
      debate for the better part of a century. There has been a particularly productive
      period recently, during which much progress has been made in better describing
      all aspects of collagen structure. However, there remain some questions regarding
      its helical symmetry and its persistence within the triple-helix. Previous
      considerations of this symmetry have sometimes confused the picture by not fully
      recognizing that collagen structure is a highly complex and large hierarchical
      entity, and this affects and is effected by the super-coiled molecules that make
      it. Nevertheless, the symmetry question is not trite, but of some significance as
      it relates to extracellular matrix organization and cellular integration. The
      correlation between helical structure in the context of the molecular packing
      arrangement determines which parts of the amino acid sequence of the collagen
      fibril are buried or accessible to the extracellular matrix or the cell. In this
      study, we concentrate primarily on the triple-helical structure of fibrillar
      collagens I and II, the two most predominant types. By comparing X-ray
      diffraction data collected from type I and type II containing tissues, we point
      to evidence for a range of triple-helical symmetries being extant in the
      molecules native environment. The possible significance of helical instability,
      local helix dissociation and molecular packing of the triple-helices is discussed
      in the context of collagen's supramolecular organization, all of which must
      affect the symmetry of the collagen triple-helix. 

PMID- 24586844
TI  - Protective effect of quercetin on the development of preimplantation mouse
      embryos against hydrogen peroxide-induced oxidative injury.
AB  - Quercetin, a plant-derived flavonoid in Chinese herbs, fruits and wine, displays
      antioxidant properties in many pathological processes associated with oxidative
      stress. However, the effect of quercetin on the development of preimplantation
      embryos under oxidative stress is unclear. The present study sought to determine
      the protective effect and underlying mechanism of action of quercetin against
      hydrogen peroxide (H2O2)-induced oxidative injury in mouse zygotes. H2O2
      treatment impaired the development of mouse zygotes in vitro, decreasing the
      rates of blastocyst formation and hatched, and increasing the fragmentation,
      apoptosis and retardation in blastocysts. Quercetin strongly protected zygotes
      from H2O2-induced oxidative injury by decreasing the reactive oxygen species
      level, maintaining mitochondrial function and modulating total antioxidant
      capability, the activity of the enzymatic antioxidants, including glutathione
      peroxidase and catalase activity to keep the cellular redox environment.
      Additionally, quercetin had no effect on the level of glutathione, the main non
      enzymatic antioxidant in embryos. 

PMID- 24586845
TI  - Squirrelpox virus: assessing prevalence, transmission and environmental
      degradation.
AB  - Red squirrels (Sciurus vulgaris) declined in Great Britain and Ireland during the
      last century, due to habitat loss and the introduction of grey squirrels (Sciurus
      carolinensis), which competitively exclude the red squirrel and act as a
      reservoir for squirrelpox virus (SQPV). The disease is generally fatal to red
      squirrels and their ecological replacement by grey squirrels is up to 25 times
      faster where the virus is present. We aimed to determine: (1) the seropositivity
      and prevalence of SQPV DNA in the invasive and native species at a regional
      scale; (2) possible SQPV transmission routes; and, (3) virus degradation rates
      under differing environmental conditions. Grey (n = 208) and red (n = 40)
      squirrel blood and tissues were sampled. Enzyme-linked immunosorbent assay
      (ELISA) and quantitative real-time polymerase chain reaction (qPCR) techniques
      established seropositivity and viral DNA presence, respectively. Overall 8% of
      squirrels sampled (both species combined) had evidence of SQPV DNA in their
      tissues and 22% were in possession of antibodies. SQPV prevalence in sampled red
      squirrels was 2.5%. Viral loads were typically low in grey squirrels by
      comparison to red squirrels. There was a trend for a greater number of positive
      samples in spring and summer than in winter. Possible transmission routes were
      identified through the presence of viral DNA in faeces (red squirrels only),
      urine and ectoparasites (both species). Virus degradation analyses suggested
      that, after 30 days of exposure to six combinations of environments, there were
      more intact virus particles in scabs kept in warm (25  degrees C) and dry
      conditions than in cooler (5 and 15  degrees C) or wet conditions. We conclude
      that SQPV is present at low prevalence in invasive grey squirrel populations with
      a lower prevalence in native red squirrels. Virus transmission could occur
      through urine especially during warm dry summer conditions but, more notably, via
      ectoparasites, which are shared by both species.

PMID- 24586846
TI  - Dynamic monitoring of mechano-sensing of cells by gold nanoslit surface plasmon
      resonance sensor.
AB  - We demonstrated a real-time monitoring of live cells upon laminar shear stress
      stimulation via surface plasmon resonance (SPR) in gold nanoslit array. A large
      area gold nanostructure consisted of 500-nm-period nanoslits was fabricated on a
      plastic film using the thermal-annealed template-stripping method. The SPR in the
      gold nanoslit array provides high surface sensitivity to monitor cell adhesion
      changes near the sensor surface. The human non-small cell lung cancer (CL1-0),
      human lung fibroblast (MRC-5), and human dermal fibroblast (Hs68) were cultured
      on the gold nanoslits and their dynamic responses to laminar shear stress were
      measured under different stress magnitudes from 0 to 30 dyne/cm(2). Cell adhesion
      was increased in CL1-0 under shear flow stimulation. No adhesion recovery was
      observed after stopping the flow. On the other hand, MRC-5 and Hs68 decreased
      adhesion and recovered from the shear stress. The degree of recovery was around
      70% for MRC-5. This device provides dynamic study and early detection of cell
      adhesion changes under shear flow conditions. 

PMID- 24586848
TI  - Reconstructing the life of an unknown (ca. 500 years-old South American Inca)
      mummy--multidisciplinary study of a Peruvian Inca mummy suggests severe Chagas
      disease and ritual homicide.
AB  - The paleopathological, paleoradiological, histological, molecular and forensic
      investigation of a female mummy (radiocarbon dated 1451-1642 AD) provides
      circumstantial evidence for massive skull trauma affecting a young adult female
      individual shortly before death along with chronic infection by Trypanosoma cruzi
      (Chagas disease). The mummy (initially assumed to be a German bog body) was
      localized by stable isotope analysis to South America at/near the
      Peruvian/Northern Chilean coast line. This is further supported by New World
      camelid fibers attached to her plaits, typical Inca-type skull deformation and
      the type of Wormian bone at her occiput. Despite an only small transverse wound
      of the supraorbital region computed tomography scans show an almost complete
      destruction of face and frontal skull bones with terrace-like margins, but
      without evidence for tissue reaction. The type of destruction indicates massive
      blunt force applied to the center of the face. Stable isotope analysis indicates
      South American origin: Nitrogen and hydrogen isotope patterns indicate an
      extraordinarily high marine diet along with C4-plant alimentation which fits best
      to the coastal area of Pacific South America. A hair strand over the last ten
      months of her life indicates a shift to a more "terrestric" nutrition pattern
      suggesting either a move from the coast or a change in her nutrition.
      Paleoradiology further shows extensive hypertrophy of the heart muscle and a
      distended large bowel/rectum. Histologically, in the rectum wall massive fibrosis
      alternates with residual smooth muscle. The latter contains multiple inclusions
      of small intracellular parasites as confirmed by immunohistochemical and
      molecular ancient DNA analysis to represent a chronic Trypanosoma cruzi
      infection. This case shows a unique paleopathological setting with massive blunt
      force trauma to the skull nurturing the hypothesis of a ritual homicide as
      previously described in South American mummies in an individual that suffered
      from severe chronic Chagas disease. 

PMID- 24586847
TI  - Magnesium inhibits Wnt/beta-catenin activity and reverses the osteogenic
      transformation of vascular smooth muscle cells.
AB  - Magnesium reduces vascular smooth muscle cell (VSMC) calcification in vitro but
      the mechanism has not been revealed so far. This work used only slightly
      increased magnesium levels and aimed at determining: a) whether inhibition of
      magnesium transport into the cell influences VSMC calcification, b) whether
      Wnt/beta-catenin signaling, a key mediator of osteogenic differentiation, is
      modified by magnesium and c) whether magnesium can influence already established
      vascular calcification. Human VSMC incubated with high phosphate (3.3 mM) and
      moderately elevated magnesium (1.4 mM) significantly reduced VSMC calcification
      and expression of the osteogenic transcription factors Cbfa-1 and osterix, and up
      regulated expression of the natural calcification inhibitors matrix Gla protein
      (MGP) and osteoprotegerin (OPG). The protective effects of magnesium on
      calcification and expression of osteogenic markers were no longer observed in
      VSMC cultured with an inhibitor of cellular magnesium transport (2-aminoethoxy
      diphenylborate [2-APB]). High phosphate induced activation of Wnt/beta-catenin
      pathway as demonstrated by the translocation of beta-catenin into the nucleus,
      increased expression of the frizzled-3 gene, and downregulation of Dkk-1 gene, a
      specific antagonist of the Wnt/beta-catenin signaling pathway. The addition of
      magnesium however inhibited phosphate-induced activation of Wnt/beta-catenin
      signaling pathway. Furthermore, TRPM7 silencing using siRNA resulted in
      activation of Wnt/beta-catenin signaling pathway. Additional experiments were
      performed to test the ability of magnesium to halt the progression of already
      established VSMC calcification in vitro. The delayed addition of magnesium
      decreased calcium content, down-regulated Cbfa-1 and osterix and up-regulated MGP
      and OPG, when compared with a control group. This effect was not observed when 2
      APB was added. In conclusion, magnesium transport through the cell membrane is
      important to inhibit VSMC calcification in vitro. Inhibition of Wnt/beta-catenin
      by magnesium is one potential intracellular mechanism by which this anti
      calcifying effect is achieved. 

PMID- 24586849
TI  - Characterization of the sialic acid binding activity of influenza A viruses using
      soluble variants of the H7 and H9 hemagglutinins.
AB  - Binding of influenza viruses to target cells is mediated by the viral surface
      protein hemagglutinin. To determine the presence of binding sites for influenza A
      viruses on cells and tissues, soluble hemagglutinins of the H7 and H9 subtype
      were generated by connecting the hemagglutinin ectodomain to the Fc portion of
      human immunoglobulin G (H7Fc and H9Fc). Both chimeric proteins bound to different
      cells and tissues in a sialic acid-dependent manner. Pronounced differences were
      observed between H7Fc and H9Fc, in the binding both to different mammalian and
      avian cultured cells and to cryosections of the respiratory epithelium of
      different virus host species (turkey, chicken and pig). Binding of the soluble
      hemagglutinins was similar to the binding of virus particles, but showed
      differences in the binding pattern when compared to two sialic acid-specific
      plant lectins. These findings were substantiated by a comparative glycan array
      analysis revealing a very narrow recognition of sialoglycoconjugates by the plant
      lectins that does not reflect the glycan structures preferentially recognized by
      H7Fc and H9Fc. Thus, soluble hemagglutinins may serve as sialic acid-specific
      lectins and are a more reliable indicator of the presence of binding sites for
      influenza virus HA than the commonly used plant lectins. 

PMID- 24586850
TI  - Maternal haemoglobin and short-term neonatal outcome in preterm neonates.
AB  - OBJECTIVE: To determine whether there is a significant association between
      maternal haemoglobin measured before delivery and short-term neonatal outcome in
      very preterm neonates. STUDY DESIGN: We included prospectively all live births
      occurring from 25 to 32+6 weeks of gestation in a tertiary care centre between
      January 1(st) 2009 and December 31(st) 2011. Outborn infants and infants
      presenting with lethal malformations were excluded. Three hundred and thirty-nine
      mothers and 409 infants met the inclusion criteria. For each mother-infant pair a
      prospective record of epidemiologic data was performed and maternal haemoglobin
      concentration recorded within 24 hours before delivery was retrospectively
      researched. Maternal haemoglobin was divided into quartiles with the second and
      the third one regarded as reference as they were composed of normal haemoglobin
      values. Short-term outcome was defined as poor in case of death during hospital
      stay and/or grades III/IV intraventricular haemorrhage and/or periventricular
      leukomalacia and/or necessity of ventriculoperitoneal shunt. RESULTS: The global
      rate of poor short-term neonatal outcome was 11.4% and was significantly
      associated with low maternal haemoglobin values. This association remained
      significant after adjustment for antenatal corticosteroids therapy, gestational
      age, parity, mechanism of preterm birth, mode of delivery and birth weight (aOR =
      2.97 CI 95% [1.36-6.47]). There was no relation between short-term neonatal
      outcome and high maternal haemoglobin concentration values. CONCLUSION: We show
      that low maternal haemoglobin concentration at delivery is an independent risk
      factor for poor short-term neonatal outcome in very preterm neonates. This study
      is one of the first to show such an association within the preterm population.

PMID- 24586851
TI  - Single cell kinetics of phenotypic switching in the arabinose utilization system
      of E. coli.
AB  - Inducible switching between phenotypes is a common strategy of bacteria to adapt
      to fluctuating environments. Here, we analyze the switching kinetics of a
      paradigmatic inducible system, the arabinose utilization system in E. coli. Using
      time-lapse fluorescence microscopy of microcolonies in a microfluidic chamber,
      which permits sudden up- and down-shifts in the inducer arabinose, we
      characterize the single-cell gene expression dynamics of the araBAD operon
      responsible for arabinose degradation. While there is significant, inducer
      dependent cell-to-cell variation in the timing of the on-switching, the off
      switching triggered by sudden removal of arabinose is homogeneous and rapid. We
      find that rapid off-switching does not depend on internal arabinose degradation.
      Because the system is regulated via the internal arabinose level sensed by AraC,
      internal arabinose must be rapidly depleted by leakage or export from the cell,
      or by degradation via a non-canonical pathway. We explored whether the poorly
      characterized membrane protein AraJ, which is part of the arabinose regulon and
      has been annotated as a possible arabinose efflux protein, is responsible for
      rapid depletion. However, we find that AraJ is not essential for rapid switching
      to the off-state. We develop a mathematical model for the arabinose system, which
      quantitatively describes both the heterogeneous on-switching and the homogeneous
      off-switching. The model also predicts that mutations which disrupt the positive
      feedback of internal arabinose on the production of arabinose uptake proteins
      change the heterogeneous on-switching behavior into a homogeneous, graded
      response. We construct such a mutant and confirm the graded response
      experimentally. Taken together, our results indicate that the physiological
      switching behavior of this sugar utilization system is asymmetric, such that off
      switching is always rapid and homogeneous, while on-switching is slow and
      heterogeneously timed at sub-saturating inducer levels. 

PMID- 24586852
TI  - Brown adipose tissue in the buccal fat pad during infancy.
AB  - BACKGROUND: The buccal fat pad (BFP) is an encapsulated mass of adipose tissue
      thought to enhance the sucking capabilities of the masticatory muscles during
      infancy. To date, no conclusive evidence has been provided as to the composition
      of the BFP in early postnatal life. OBJECTIVE: The purpose of this study was to
      examine whether the BFP of neonates and infants is primarily composed of white
      adipose tissue (WAT) or brown adipose tissue (BAT). MATERIALS AND METHODS: The
      percentage of fat in the BFP in 32 full-term infants (16 boys and 16 girls), aged
      one day to 10.6 months, was measured using magnetic resonance imaging (MRI)
      determinations of fat fraction. RESULTS: BFP fat fraction increased with age (r =
      0.67; P<.0001) and neonates had significantly lower values when compared to older
      infants; 72.6 +/- 9.6 vs. 91.8 +/- 2.4, P<.0001. Multiple regression analysis
      indicated that the age-dependent relationship persisted after accounting for
      gender, gestational age, and weight percentile (P = .001). Two subjects (aged one
      and six days) depicted a change in the MRI characteristics of the BFP from
      primarily BAT to WAT at follow-up examinations two to six weeks later,
      respectively. Histological post-mortem studies of a 3 day and 1.1 month old
      revealed predominantly BAT and WAT in the BFP, respectively. CONCLUSION: The BFP
      is primarily composed of BAT during the first weeks of life, but of WAT
      thereafter. Studies are needed to investigate the contributions of BAT in the BFP
      to infant feeding and how it is altered by postnatal nutrition.

PMID- 24586853
TI  - Exosomes: decreased sensitivity of lung cancer A549 cells to cisplatin.
AB  - Exosomes are small extracellular membrane vesicles of endocytic origin released
      by many cells that could be found in most body fluids. The main functions of
      exosomes are cellular communication and cellular waste clean-up. This study was
      conducted to determine the involvement of exosomes in the regulation of
      sensitivity of the lung cancer cell line A549 to cisplatin (DDP). When DDP was
      added to A549 cells, exosomes secretion was strengthened. Addition of the
      secreted exosomes to other A549 cells increased the resistance of these A549
      cells to DDP. Upon exposure of A549 to DDP, the expression levels of several
      miRNAs and mRNAs reportedly associated with DDP sensitivity changed significantly
      in exosomes; these changes may mediate the resistance of A549 cells to DDP.
      Exosomes released by A549 cells during DDP exposure decreased the sensitivity of
      other A549 cells to DDP, which may be mediated by miRNAs and mRNAs exchange by
      exosomes via cell-to-cell communication. Although the detailed mechanism of
      resistance remains unclear, we believed that inhibition of exosomes formation and
      release might present a novel strategy for lung cancer treatment in the future. 

PMID- 24586855
TI  - A class of ratio estimators of a finite population mean using two auxiliary
      variables.
AB  - In sample surveys, it is usual to increase the efficiency of the estimators by
      the use of the auxiliary information. We propose a class of ratio estimators of a
      finite population mean using two auxiliary variables and obtain mean square error
      (MSE) equations for the class of proposed estimators. We find theoretical
      conditions that make proposed family estimators more efficient than the
      traditional ratio estimator and the estimators proposed by Abu-Dayeh et al. using
      two auxiliary variables. In addition, we support these theoretical results with
      the aid of a numerical example. 

PMID- 24586854
TI  - Subclinical atherosclerosis among HIV-infected adults attending HIV/AIDS care at
      two large ambulatory HIV clinics in Uganda.
AB  - BACKGROUND: The increased immune activation and inflammation of chronic HIV
      infection and the characteristic dyslipidemias associated with HIV infection and
      antiretroviral therapy (ART) contribute to an increased risk of atherosclerotic
      vascular disease among HIV-infected adults. There is an emerging need to
      understand determinants of cardiovascular disease (CVD) among individuals aging
      with HIV in sub-Saharan Africa. We determined the prevalence of subclinical
      atherosclerosis [carotid intima media thickness (CIMT) >= 0.78 mm] and its
      correlation with traditional CVD risk factors among HIV-infected adults. METHODS:
      In a cross-sectional study, HIV-infected adults (ART-naive and ART-treated) were
      consecutively selected from patients' enrollment registers at two large HIV
      clinics at Mulago Hospital, Kampala, Uganda. We measured traditional CVD risk
      factors including age, biophysical profile, fasting blood sugar and serum lipid
      profile as well as biomarkers of inflammation. High resolution ultrasound was
      used to measure common carotid CIMT. RESULTS: Of 245 patients, Median age
      [Interquartile range (IQR)] 37 years (31-43), 168 (69%) were females; and 100
      (41%) were ART-treated for at least 7 years. Overall, 34/186 (18%) had
      subclinical atherosclerosis; of whom 15/108 (14%) were ART-naive whereas 19/78
      (24%) were ART-treated. Independent predictors of subclinical atherosclerosis
      included age [odds ratio (OR) 1.83 per 5-year increase in age; 95% confidence
      interval (CI) 1.24-2.69; p = 0.002], body mass index (BMI); OR 1.15; CI 1.01
      1.31; p = 0.041 and high low density lipoprotein (LDL) [OR 2.99; CI 1.02-8.78, p
      = 0.046]. High sensitivity C-reactive protein (hsCRP) was positively correlated
      with traditional cardio-metabolic risk factors including waist circumference (r =
      0.127, p = 0.05), triglycerides (r = 0.19, p = 0.003) and Total Cholesterol: High
      Density Lipoprotein ratio (TC:LDL) (r = 0.225, p<0.001). CONCLUSION: The
      prevalence of subclinical atherosclerosis was 18% among HIV-infected adults in
      Uganda. Traditional CVD risk factors were associated with subclinical
      atherosclerosis. We recommend routine assessment of traditional CVD risk factors
      within HIV care and treatment programs in sub-Saharan Africa.

PMID- 24586856
TI  - Genome-wide identification of genes essential for the survival of Streptococcus
      pneumoniae in human saliva.
AB  - Since Streptococcus pneumoniae transmits through droplet spread, this respiratory
      tract pathogen may be able to survive in saliva. Here, we show that saliva
      supports survival of clinically relevant S. pneumoniae strains for more than 24 h
      in a capsule-independent manner. Moreover, saliva induced growth of S. pneumoniae
      in growth-permissive conditions, suggesting that S. pneumoniae is well adapted
      for uptake of nutrients from this bodily fluid. By using Tn-seq, a method for
      genome-wide negative selection screening, we identified 147 genes potentially
      required for growth and survival of S. pneumoniae in saliva, among which genes
      predicted to be involved in cell envelope biosynthesis, cell transport, amino
      acid metabolism, and stress response predominated. The Tn-seq findings were
      validated by testing a panel of directed gene deletion mutants for their ability
      to survive in saliva under two testing conditions: at room temperature without
      CO2, representing transmission, and at 37  degrees C with CO2, representing in
      host carriage. These validation experiments confirmed that the plsX gene and the
      amiACDEF and aroDEBC operons, involved in respectively fatty acid metabolism,
      oligopeptide transport, and biosynthesis of aromatic amino acids play an
      important role in the growth and survival of S. pneumoniae in saliva at 37 
      degrees C. In conclusion, this study shows that S. pneumoniae is well-adapted for
      growth and survival in human saliva and provides a genome-wide list of genes
      potentially involved in adaptation. This notion supports earlier evidence that S.
      pneumoniae can use human saliva as a vector for transmission.

PMID- 24586857
TI  - Dermal substitutes support the growth of human skin-derived mesenchymal stromal
      cells: potential tool for skin regeneration.
AB  - New strategies for skin regeneration are needed in order to provide effective
      treatment for cutaneous wounds and disease. Mesenchymal stem cells (MSCs) are an
      attractive source of cells for tissue engineering because of their prolonged self
      renewal capacity, multipotentiality, and ability to release active molecules
      important for tissue repair. In this paper, we show that human skin-derived
      mesenchymal stromal cells (SD-MSCs) display similar characteristics to the
      multipotent MSCs. We also evaluate their growth in a three-dimensional (3D)
      culture system with dermal substitutes (Integra and Pelnac). When cultured in
      monolayers, SD-MSCs expressed mesenchymal markers, such as CD105, Fibronectin,
      and alpha-SMA; and neural markers, such as Nestin and betaIII-Tubulin; at
      transcriptional and/or protein level. Integra and Pelnac equally supported the
      adhesion, spread and growth of human SD-MSCs in 3D culture, maintaining the MSC
      characteristics and the expression of multilineage markers. Therefore, dermal
      substitutes support the growth of mesenchymal stromal cells from human skin,
      promising an effective tool for tissue engineering and regenerative technology. 

PMID- 24586858
TI  - Automatic detection of key innovations, rate shifts, and diversity-dependence on
      phylogenetic trees.
AB  - A number of methods have been developed to infer differential rates of species
      diversification through time and among clades using time-calibrated phylogenetic
      trees. However, we lack a general framework that can delineate and quantify
      heterogeneous mixtures of dynamic processes within single phylogenies. I
      developed a method that can identify arbitrary numbers of time-varying
      diversification processes on phylogenies without specifying their locations in
      advance. The method uses reversible-jump Markov Chain Monte Carlo to move between
      model subspaces that vary in the number of distinct diversification regimes. The
      model assumes that changes in evolutionary regimes occur across the branches of
      phylogenetic trees under a compound Poisson process and explicitly accounts for
      rate variation through time and among lineages. Using simulated datasets, I
      demonstrate that the method can be used to quantify complex mixtures of time
      dependent, diversity-dependent, and constant-rate diversification processes. I
      compared the performance of the method to the MEDUSA model of rate variation
      among lineages. As an empirical example, I analyzed the history of speciation and
      extinction during the radiation of modern whales. The method described here will
      greatly facilitate the exploration of macroevolutionary dynamics across large
      phylogenetic trees, which may have been shaped by heterogeneous mixtures of
      distinct evolutionary processes. 

PMID- 24586859
TI  - Nonword repetition--a clinical marker for specific language impairment in Swedish
      associated with parents' language-related problems.
AB  - First, we explore the performance of nonword repetition (NWR) in children with
      specific language impairment (SLI) and typically developing children (TD) in
      order to investigate the accuracy of NWR as a clinical marker for SLI in Swedish
      speaking school-age children. Second, we examine the relationship between NWR,
      family aggregation, and parental level of education in children with SLI. A
      sample of 61 children with SLI, and 86 children with TD, aged 8-12 years, were
      administered an NWR test. Family aggregation, measured as the prevalence of
      language and/or literacy problems (LLP) in parents of the children with SLI, was
      based on family history interviews. The sensitivity and specificity of nonword
      repetition was analyzed in a binary logistic regression, cut-off values were
      established with ROC curves, and positive and negative likelihood ratios
      reported. Results from the present study show that NWR distinguishes well between
      Swedish-speaking school-children with and without SLI. We found 90.2% sensitivity
      and 97.7% specificity at a cut-off level of -2 standard deviations for binary
      scoring of nonwords. Differences between the SLI and TD groups showed large
      effect sizes for the two scoring measures binary (d = 2.11) and percent correct
      consonants (PCC) (d = 1.79). The children with SLI were split into two subgroups:
      those with no parents affected with LLP (n = 12), and those with one or both
      parents affected (n = 49). The subgroup consisting of affected parents had a
      significantly lower score on NWR binary (p = .037), and there was a great
      difference between the subgroups (d = 0.7). When compared to the TD group, the
      difference from the subgroup with affected parents was almost one standard
      deviation larger (d = 2.47) than the difference from the TD to the subgroup
      consisting of non-affected parents (d = 1.57). Our study calls for further
      exploration of the complex interaction between family aggregation, language
      input, and phenotypes of SLI. 

PMID- 24586860
TI  - Expression and differentiation between OCT4A and its Pseudogenes in human ESCs
      and differentiated adult somatic cells.
AB  - The POU5F1 gene codes for the OCT4 transcription factor, which is one of the key
      regulators of pluripotency. Its transcription, alternative splicing, and
      alternative translation leading to the synthesis of the active, nuclear localized
      OCT4A has been described in detail. Much less, however, is known about actively
      transcribed OCT4 pseudogenes, several of which display high homology to OCT4A and
      can be expressed and translated into proteins. Using RT-PCR followed by
      pseudogene-specific restriction digestion, cloning, and sequencing we
      discriminate between OCT4A and transcripts for pseudogenes 1, 3 and 4. We show
      that expression of OCT4 and its pseudogenes follows a developmentally-regulated
      pattern in differentiating hESCs, indicating a tight regulatory relationship
      between them. We further demonstrate that differentiated human cells from a
      variety of tissues express exclusively pseudogenes. Expression of OCT4A can,
      however be triggered in adult differentiated cells by oxygen and FGF2-dependent
      mechanisms. 

PMID- 24586861
TI  - The catalytic subunit of the system L1 amino acid transporter (slc7a5)
      facilitates nutrient signalling in mouse skeletal muscle.
AB  - The System L1-type amino acid transporter mediates transport of large neutral
      amino acids (LNAA) in many mammalian cell-types. LNAA such as leucine are
      required for full activation of the mTOR-S6K signalling pathway promoting protein
      synthesis and cell growth. The SLC7A5 (LAT1) catalytic subunit of high-affinity
      System L1 functions as a glycoprotein-associated heterodimer with the
      multifunctional protein SLC3A2 (CD98). We generated a floxed Slc7a5 mouse strain
      which, when crossed with mice expressing Cre driven by a global promoter,
      produced Slc7a5 heterozygous knockout (Slc7a5+/-) animals with no overt
      phenotype, although homozygous global knockout of Slc7a5 was embryonically
      lethal. Muscle-specific (MCK Cre-mediated) Slc7a5 knockout (MS-Slc7a5-KO) mice
      were used to study the role of intracellular LNAA delivery by the SLC7A5
      transporter for mTOR-S6K pathway activation in skeletal muscle. Activation of
      muscle mTOR-S6K (Thr389 phosphorylation) in vivo by intraperitoneal leucine
      injection was blunted in homozygous MS-Slc7a5-KO mice relative to wild-type
      animals. Dietary intake and growth rate were similar for MS-Slc7a5-KO mice and
      wild-type littermates fed for 10 weeks (to age 120 days) with diets containing
      10%, 20% or 30% of protein. In MS-Slc7a5-KO mice, Leu and Ile concentrations in
      gastrocnemius muscle were reduced by ~40% as dietary protein content was reduced
      from 30 to 10%. These changes were associated with >50% decrease in S6K Thr389
      phosphorylation in muscles from MS-Slc7a5-KO mice, indicating reduced mTOR-S6K
      pathway activation, despite no significant differences in lean tissue mass
      between groups on the same diet. MS-Slc7a5-KO mice on 30% protein diet exhibited
      mild insulin resistance (e.g. reduced glucose clearance, larger gonadal adipose
      depots) relative to control animals. Thus, SLC7A5 modulates LNAA-dependent muscle
      mTOR-S6K signalling in mice, although it appears non-essential (or is
      sufficiently compensated by e.g. SLC7A8 (LAT2)) for maintenance of normal muscle
      mass. 

PMID- 24586862
TI  - RAGE regulates immune cell infiltration and angiogenesis in choroidal
      neovascularization.
AB  - PURPOSE: RAGE regulates pro-inflammatory responses in diverse cells and tissues.
      This study has investigated if RAGE plays a role in immune cell mobilization and
      choroidal neovascular pathology that is associated with the neovascular form of
      age-related macular degeneration (nvAMD). METHODS: RAGE null (RAGE-/-) mice and
      age-matched wild type (WT) control mice underwent laser photocoagulation to
      generate choroidal neovascularization (CNV) lesions which were then analyzed for
      morphology, S100B immunoreactivity and inflammatory cell infiltration. The
      chemotactic ability of bone marrow derived macrophages (BMDMs) towards S100B was
      investigated. RESULTS: RAGE expression was significantly increased in the retina
      during CNV of WT mice (p<0.001). RAGE-/- mice exhibited significantly reduced CNV
      lesion size when compared to WT controls (p<0.05). S100B mRNA was upregulated in
      the lasered WT retina but not RAGE-/- retina and S100B immunoreactivity was
      present within CNV lesions although levels were less when RAGE-/- mice were
      compared to WT controls. Activated microglia in lesions were considerably less
      abundant in RAGE-/- mice when compared to WT counterparts (p<0.001). A dose
      dependent chemotactic migration was observed in BMDMs from WT mice (p<0.05-0.01)
      but this was not apparent in cells isolated from RAGE-/- mice. CONCLUSIONS: RAGE
      S100B interactions appear to play an important role in CNV lesion formation by
      regulating pro-inflammatory and angiogenic responses. This study highlights the
      role of RAGE in inflammation-mediated outer retinal pathology.

PMID- 24586864
TI  - Child feces disposal practices in rural Orissa: a cross sectional study.
AB  - BACKGROUND: An estimated 2.5 billion people worldwide lack access to improved
      sanitation facilities. While large-scale programs in some countries have
      increased latrine coverage, they sometimes fail to ensure optimal latrine use,
      including the safe disposal of child feces, a significant source of exposure to
      fecal pathogens. We undertook a cross-sectional study to explore fecal disposal
      practices among children in rural Orissa, India in villages where the Government
      of India's Total Sanitation Campaign had been implemented at least three years
      prior to the study. METHODS AND FINDINGS: We conducted surveys with heads of 136
      households with 145 children under 5 years of age in 20 villages. We describe
      defecation and feces disposal practices and explore associations between safe
      disposal and risk factors. Respondents reported that children commonly defecated
      on the ground, either inside the household (57.5%) for pre-ambulatory children or
      around the compound (55.2%) for ambulatory children. Twenty percent of pre
      ambulatory children used potties and nappies; the same percentage of ambulatory
      children defecated in a latrine. While 78.6% of study children came from 106
      households with a latrine, less than a quarter (22.8%) reported using them for
      disposal of child feces. Most child feces were deposited with other household
      waste, both for pre-ambulatory (67.5%) and ambulatory (58.1%) children. After
      restricting the analysis to households owning a latrine, the use of a nappy or
      potty was associated with safe disposal of feces (OR 6.72, 95%CI 1.02-44.38)
      though due to small sample size the regression could not adjust for confounders.
      CONCLUSIONS: In the area surveyed, the Total Sanitation Campaign has not led to
      high levels of safe disposal of child feces. Further research is needed to
      identify the actual scope of this potential gap in programming, the health risk
      presented and interventions to minimize any adverse effect.

PMID- 24586863
TI  - Functional tradeoffs underpin salinity-driven divergence in microbial community
      composition.
AB  - Bacterial community composition and functional potential change subtly across
      gradients in the surface ocean. In contrast, while there are significant
      phylogenetic divergences between communities from freshwater and marine habitats,
      the underlying mechanisms to this phylogenetic structuring yet remain unknown. We
      hypothesized that the functional potential of natural bacterial communities is
      linked to this striking divide between microbiomes. To test this hypothesis,
      metagenomic sequencing of microbial communities along a 1,800 km transect in the
      Baltic Sea area, encompassing a continuous natural salinity gradient from limnic
      to fully marine conditions, was explored. Multivariate statistical analyses
      showed that salinity is the main determinant of dramatic changes in microbial
      community composition, but also of large scale changes in core metabolic
      functions of bacteria. Strikingly, genetically and metabolically different
      pathways for key metabolic processes, such as respiration, biosynthesis of
      quinones and isoprenoids, glycolysis and osmolyte transport, were differentially
      abundant at high and low salinities. These shifts in functional capacities were
      observed at multiple taxonomic levels and within dominant bacterial phyla, while
      bacteria, such as SAR11, were able to adapt to the entire salinity gradient. We
      propose that the large differences in central metabolism required at high and low
      salinities dictate the striking divide between freshwater and marine microbiomes,
      and that the ability to inhabit different salinity regimes evolved early during
      bacterial phylogenetic differentiation. These findings significantly advance our
      understanding of microbial distributions and stress the need to incorporate
      salinity in future climate change models that predict increased levels of
      precipitation and a reduction in salinity. 

PMID- 24586865
TI  - Involvement of KLF11 in hepatic glucose metabolism in mice via suppressing of
      PEPCK-C expression.
AB  - BACKGROUND: Abnormal hepatic gluconeogenesis is related to hyperglycemia in
      mammals with insulin resistance. Despite the strong evidences linking Kruppel
      like factor 11 (KLF11) gene mutations to development of Type 2 diabetes, the
      precise physiological functions of KLF11 in vivo remain largely unknown. RESULTS:
      In current investigation, we showed that KLF11 is involved in modulating hepatic
      glucose metabolism in mice. Overexpression of KLF11 in primary mouse hepatocytes
      could inhibit the expression of gluconeogenic genes, including
      phosphoenolpyruvate carboxykinase (cytosolic isoform, PEPCK-C) and peroxisome
      proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha),
      subsequently decreasing the cellular glucose output. Diabetic mice with
      overexpression of KLF11 gene in livers significantly ameliorated hyperglycemia
      and glucose intolerance; in contrast, the knockdown of KLF11 expression in db/m
      and C57BL/6J mice livers impaired glucose tolerance. CONCLUSIONS: Our data
      strongly indicated the involvement of KLF11 in hepatic glucose homeostasis via
      modulating the expression of PEPCK-C.

PMID- 24586866
TI  - Mutation or loss of p53 differentially modifies TGFbeta action in ovarian cancer.
AB  - Ovarian cancer is the most lethal gynecological disease affecting women in the
      US. The Cancer Genome Atlas Network identified p53 mutations in 96% of high-grade
      serous ovarian carcinomas, demonstrating its critical role. Additionally, the
      Transforming Growth Factor Beta (TGFbeta) pathway is dysfunctional in various
      malignancies, including ovarian cancer. This study investigated how expression of
      wild-type, mutant, or the absence of p53 alters ovarian cancer cell response to
      TGFbeta signaling, as well as the response of the ovarian surface epithelium and
      the fallopian tube epithelium to TGFbeta. Only ovarian cancer cells expressing
      wild-type p53 were growth inhibited by TGFbeta, while ovarian cancer cells that
      were mutant or null p53 were not. TGFbeta induced migration in p53 null SKOV3
      cells, which was not observed in SKOV3 cells with stable expression of mutant p53
      R273H. Knockdown of wild-type p53 in the OVCA 420 ovarian cancer cells enhanced
      cell migration in response to TGFbeta. Increased protein expression of DKK1 and
      TMEPAI, two pro-invasive genes with enhanced expression in late stage metastatic
      ovarian cancer, was observed in p53 knockdown and null cells, while cells stably
      expressing mutant p53 demonstrated lower DKK1 and TMEPAI induction. Expression of
      mutant p53 or loss of p53 permit continued proliferation of ovarian cancer cell
      lines in the presence of TGFbeta; however, cells expressing mutant p53 exhibit
      reduced migration and decreased protein levels of DKK1 and TMEPAI. 

PMID- 24586867
TI  - Barriers and facilitators for the implementation of primary prevention and health
      promotion activities in primary care: a synthesis through meta-ethnography.
AB  - BACKGROUND: Evidence supports the implementation of primary prevention and health
      promotion (PP&HP) activities but primary care (PC) professionals show resistance
      to implementing these activities. The aim was to synthesize the available
      qualitative research on barriers and facilitators identified by PC physicians and
      nurses in the implementation of PP&HP in adults. METHODS AND FINDINGS: A
      systematic search of three databases was conducted and supported by manual
      searches. The 35 articles included were translated into each other and a new
      interpretation of the concepts extracted was generated. The factors affecting the
      implementation of PP&HP activities in PC according to professionals were fitted
      into a five-level ecological model: intrapersonal factors, interpersonal
      processes, institutional factors, community factors and public policy. At the
      intrapersonal level we find professionals' beliefs about PP&HP, experiences,
      skills and knowledge, and selfconcept. The attitudes and behavior towards PP&HP
      of patients, specialists, practice managers and colleagues (interpersonal
      factors) affect the feasibility of implementing PP&HP. Institutional level: PC is
      perceived as well-placed to implement PP&HP but workload, lack of time and
      referral resources, and the predominance of the biomedical model (which
      prioritizes disease treatment) hamper the implementation of PP&HP. The
      effectiveness of financial incentives and tools such as guidelines and
      alarms/reminders is conditioned by professionals' attitudes to them. Community
      factors include patients' social and cultural characteristics (religion,
      financial resources, etc.), local referral resources, mass-media messages and
      pharmaceutical industry campaigns, and the importance given to PP&HP in the
      curriculum in university. Finally, policies affect the distribution of resources,
      thus affecting the implementation of PP&HP. CONCLUSIONS: Research on barriers and
      facilitators in the implementation of PP&HP activities in multirisk management is
      scarce. The conceptual overview provided by this synthesis resulted in the
      development of practical recommendations for the design of PP&HP in PC. However,
      the effectiveness of these recommendations needs to be demonstrated.

PMID- 24586868
TI  - Early growth inhibition is followed by increased metastatic disease with vitamin
      D (calcitriol) treatment in the TRAMP model of prostate cancer.
AB  - The active metabolite of vitamin D3, 1,25-dihydroxyvitamin D3 (calcitriol) has
      antiproliferative effects in non-aggressive prostate cancer, however, its effects
      in more aggressive model systems are still unclear. In these studies, effects of
      calcitriol and a less-calcemic vitamin D analog, QW-1624F2-2 (QW), were tested in
      vivo, using the aggressive autochthonous transgenic adenocarcinoma of mouse
      prostate (TRAMP) model. To study prevention of androgen-stimulated prostate
      cancer, vehicle, calcitriol (20 ug/kg), or QW (50 ug/kg) were administered to 4
      week-old TRAMP mice intraperitoneal (i.p.) 3*/week on a MWF schedule for 14
      weeks. Calcitriol and QW slowed progression of prostate cancer as indicated by
      reduced urogenital tract (p = 0.0022, calcitriol; p = 0.0009, QW) and prostate
      weights (p = 0.0178, calcitriol; p = 0.0086, QW). However, only calcitriol
      increased expression of the pro-differentiation marker, cadherin 1 (p = 0.0086),
      and reduced tumor proliferation (p = 0.0467). By contrast, neither vitamin D
      analog had any effect on castration resistant prostate cancer in mice treated pre
      or post-castration. Interestingly, although vitamin D showed inhibitory activity
      against primary tumors in hormone-intact mice, distant organ metastases seemed to
      be enhanced following treatment (p = 0.0823). Therefore, TRAMP mice were treated
      long-term with calcitriol to further examine effects on metastasis. Calcitriol
      significantly increased the number of distant organ metastases when mice were
      treated from 4 weeks-of-age until development of palpable tumors (20-25 weeks-of
      age)(p = 0.0003). Overall, data suggest that early intervention with vitamin D in
      TRAMP slowed androgen-stimulated tumor progression, but prolonged treatment
      resulted in development of a resistant and more aggressive disease associated
      with increased distant organ metastasis. 

PMID- 24586869
TI  - Early effects of neutering on energy expenditure in adult male cats.
AB  - The initial cause of post-neutering weight gain in male cats is not entirely
      known. There is evidence that energy intake (EI) increases rapidly post
      neutering, but it is not clear if neutering also decreases energy expenditure
      (EE) prior to weight gain. Thus, the purpose of this study was to determine if a
      decrease in EE contributes to the initial shift toward positive energy balance in
      neutered male cats. To determine the influence of neutering on EE independent of
      changes in EI and body weight (BW), male cats were fed at their pre-neutering
      maintenance EI and EE was measured at 4 days pre-neutering, 3-4 days post
      neutering, and 9 days post- neutering. Ad libitum food access was then provided
      for 6 months. Body composition was measured and blood samples collected for serum
      chemistry at pre-neutering and 7 days, 13 days and 6 months post-neutering. Total
      energy expenditure (TEE) adjusted for lean body mass (LBM) did not change in cats
      from pre-neutering to 9 days post-neutering. However, TEE adjusted for BW and
      resting energy expenditure adjusted for either LBM or BW showed a small, but
      significant (P<0.05) increase from pre-neutering to 9 days post-neutering. When
      allowed free choice food access, cats showed significant increases of food intake
      (FI) and BW. Circulating concentrations of ghrelin increased, while adiponectin
      levels decreased following neutering. The results of this study indicate that
      initial post-neutering weight gain in male cats results from increased FI and not
      decreased EE. Long-term control of FI should be initiated after neutering to
      prevent hyperphagia and weight gain in male cats. 

PMID- 24586870
TI  - SAMHD1 restricts HIV-1 replication and regulates interferon production in mouse
      myeloid cells.
AB  - SAMHD1 restricts the replication of HIV-1 and other retroviruses in human myeloid
      and resting CD4(+) T cells and that is counteracted in SIV and HIV-2 by the Vpx
      accessory protein. The protein is a phosphohydrolase that lowers the
      concentration of deoxynucleoside triphosphates (dNTP), blocking reverse
      transcription of the viral RNA genome. Polymorphisms in the gene encoding SAMHD1
      are associated with Aicardi-Goutieres Syndrome, a neurological disorder
      characterized by increased type-I interferon production. SAMHD1 is conserved in
      mammals but its role in restricting virus replication and controlling interferon
      production in non-primate species is not well understood. We show that SAMHD1 is
      catalytically active and expressed at high levels in mouse spleen, lymph nodes,
      thymus and lung. siRNA knock-down of SAMHD1 in bone marrow-derived macrophages
      increased their susceptibility to HIV-1 infection. shRNA knock-down of SAMHD1 in
      the murine monocytic cell-line RAW264.7 increased its susceptibility to HIV-1 and
      murine leukemia virus and increased the levels of the dNTP pool. In addition,
      SAMHD1 knock-down in RAW264.7 cells induced the production of type-I interferon
      and several interferon-stimulated genes, modeling the situation in Aicardi
      Goutieres Syndrome. Our findings suggest that the role of SAMHD1 in restricting
      viruses is conserved in the mouse. The RAW264.7 cell-line serves as a useful tool
      to study the antiviral and innate immune response functions of SAMHD1. 

PMID- 24586871
TI  - Effect of transverse aortic constriction on cardiac structure, function and gene
      expression in pregnant rats.
AB  - BACKGROUND: There is an increased risk of heart failure and pulmonary edema in
      pregnancies complicated by hypertensive disorders. However, in a previous study
      we found that pregnancy protects against fibrosis and preserves angiogenesis in a
      rat model of angiotensin II induced cardiac hypertrophy. In this study we test
      the hypothesis that pregnancy protects against negative effects of increased
      afterload. METHODS: Pregnant (gestational day 5.5-8.5) and non-pregnant Wistar
      rats were randomized to transverse aortic constriction (TAC) or sham surgery.
      After 14.2 +/- 0.14 days echocardiography was performed. Aortic blood pressure
      and left ventricular (LV) pressure-volume loops were obtained using a conductance
      catheter. LV collagen content and cardiomyocyte circumference were measured.
      Myocardial gene expression was assessed by real-time polymerase chain reaction.
      RESULTS: Heart weight was increased by TAC (p<0.001) but not by pregnancy.
      Cardiac myocyte circumference was larger in pregnant compared to non-pregnant
      rats independent of TAC (p = 0.01), however TAC per se did not affect this
      parameter. Collagen content in LV myocardium was not affected by pregnancy or
      TAC. TAC increased stroke work more in pregnant rats (34.1 +/- 2.4 vs 17.5 +/-
      2.4 mmHg/mL, p<0.001) than in non-pregnant (28.2 +/- 1.7 vs 20.9 +/- 1.5 mmHg/mL,
      p = 0.06). However, it did not lead to overt heart failure in any group. In
      pregnant rats, alpha-MHC gene expression was reduced by TAC. Increased in the
      expression of beta-MHC gene was higher in pregnant (5-fold) compared to non
      pregnant rats (2-fold) after TAC (p = 0.001). Nine out of the 19 genes related to
      cardiac remodeling were affected by pregnancy independent of TAC. CONCLUSIONS:
      This study did not support the hypothesis that pregnancy is cardioprotective
      against the negative effects of increased afterload. Some differences in cardiac
      structure, function and gene expression between pregnant and non-pregnant rats
      following TAC indicated that afterload increase is less tolerated in pregnancy.

PMID- 24586872
TI  - Blockade of the programmed death-1 (PD1) pathway undermines potent genetic
      protection from type 1 diabetes.
AB  - AIMS/HYPOTHESIS: Inhibition of PD1-PDL1 signaling in NOD mice accelerates onset
      of type 1 diabetes implicating this pathway in suppressing the emergence of
      pancreatic beta cell reactive T-cells. However, the molecular mechanism by which
      PD1 signaling protects from type 1 diabetes is not clear. We hypothesized that
      differential susceptibility of Idd mouse strains to type 1 diabetes when
      challenged with anti PDL1 will identify genomic loci that collaborate with PD1
      signaling in suppressing type 1 diabetes. METHODS: Anti PDL1 was administered to
      NOD and various Idd mouse strains at 10 weeks of age and onset of disease was
      monitored by measuring blood glucose levels. Additionally, histological
      evaluation of the pancreas was performed to determine degree of insulitis.
      Statistical analysis of the data was performed using Log-Rank and Student's t
      test. RESULTS: Blockade of PDL1 rapidly precipitated type 1 diabetes in nearly
      all NOD Idd congenic strains tested, despite the fact that all are moderately
      (Idd5, Idd3 and Idd10/18) or highly (Idd3/10/18 and Idd9) protected from
      spontaneous type 1 diabetes by virtue of their protective Idd genes. Only the
      Idd3/5 strain, which is nearly 100% protected from spontaneous disease, remained
      normoglycemic following PDL1 blockade. CONCLUSIONS: These results indicate that
      multiple Idd loci collaborate with PD1 signaling. Anti PDL1 treatment undermines
      a large portion of the genetic protection mediated by Idd genes in the NOD model
      of type 1 diabetes. Basal insulitis correlated with higher susceptibility to type
      1 diabetes. These findings have important implications since the PD1 pathway is a
      target for immunotherapy.

PMID- 24586873
TI  - Apolipoprotein E plays a key role against cryptosporidial infection in transgenic
      undernourished mice.
AB  - Apolipoliprotein E (apoE), a critical targeting protein in lipid homeostasis, has
      been found to have immunoinflammatory effects on murine models of infection and
      malnutrition. The effects of apoE in undernourished and Cryptosporidium parvum
      infected mice have not been investigated. In order to study the role of apoE in a
      model of C. parvum infection, we used the following C57BL6J mouse genetic
      strains: APOE-deficient, wild-type controls, and APOE targeted replacement (TR)
      mice expressing human APOE genes (E3/3; E4/4). Experimental mice were orally
      infected with 10(7)-unexcysted-C. parvum oocysts between post-natal days 34-35
      followed by malnutrition induced with a low-protein diet. Mice were euthanized
      seven days after C. parvum-challenge to investigate ileal morphology, cytokines,
      and cationic arginine transporter (CAT-1), arginase 1, Toll-like receptor 9
      (TLR9), and inducible nitric oxide synthase (iNOS) expression. In addition, we
      analyzed stool oocyst shedding by qRT-PCR and serum lipids. APOE4/4-TR mice had
      better weight gains after infection plus malnutrition compared with APOE3/3-TR
      and wild-type mice. APOE4/4-TR and APOE knockout mice had lower oocyst shedding,
      however the latter exhibited with villus blunting and higher ileal pro
      inflammatory cytokines and iNOS transcripts. APOE4/4-TR mice had increased ileal
      CAT-1, arginase-1, and TLR9 transcripts relative to APOE knockout. Although with
      anti-parasitic effects, APOE deficiency exacerbates intestinal inflammatory
      responses and mucosal damage in undernourished and C. parvum-infected mice. In
      addition, the human APOE4 gene was found to be protective against the compounded
      insult of Cryptosporidium infection plus malnutrition, thus extending our
      previous findings of the protection against diarrhea in APOE4 children.
      Altogether our findings suggest that apoE plays a key role in the intestinal
      restitution and immunoinflammatory responses with Cryptosporidium infection and
      malnutrition. 

PMID- 24586874
TI  - Local anesthetics induce apoptosis in human thyroid cancer cells through the
      mitogen-activated protein kinase pathway.
AB  - Local anesthetics are frequently used in fine-needle aspiration of thyroid
      lesions and locoregional control of persistent or recurrent thyroid cancer.
      Recent evidence suggests that local anesthetics have a broad spectrum of effects
      including inhibition of cell proliferation and induction of apoptosis in neuronal
      and other types of cells. In this study, we demonstrated that treatment with
      lidocaine and bupivacaine resulted in decreased cell viability and colony
      formation of both 8505C and K1 cells in a dose-dependent manner. Lidocaine and
      bupivacaine induced apoptosis, and necrosis in high concentrations, as determined
      by flow cytometry. Lidocaine and bupivacaine caused disruption of mitochondrial
      membrane potential and release of cytochrome c, accompanied by activation of
      caspase 3 and 7, PARP cleavage, and induction of a higher ratio of Bax/Bcl-2.
      Based on microarray and pathway analysis, apoptosis is the prominent
      transcriptional change common to lidocaine and bupivacaine treatment.
      Furthermore, lidocaine and bupivacaine attenuated extracellular signal-regulated
      kinase 1/2 (ERK1/2) activity and induced activation of p38 mitogen-activated
      protein kinase (MAPK) and c-jun N-terminal kinase. Pharmacological inhibitors of
      MAPK/ERK kinase and p38 MAPK suppressed caspase 3 activation and PARP cleavage.
      Taken together, our results for the first time demonstrate the cytotoxic effects
      of local anesthetics on thyroid cancer cells and implicate the MAPK pathways as
      an important mechanism. Our findings have potential clinical relevance in that
      the use of local anesthetics may confer previously unrecognized benefits in the
      management of patients with thyroid cancer. 

PMID- 24586875
TI  - A systems biology approach to the characterization of stress response in
      Dermacentor reticulatus tick unfed larvae.
AB  - BACKGROUND: Dermacentor reticulatus (Fabricius, 1794) is distributed in Europe
      and Asia where it infests and transmits disease-causing pathogens to humans, pets
      and other domestic and wild animals. However, despite its role as a vector of
      emerging or re-emerging diseases, very little information is available on the
      genome, transcriptome and proteome of D. reticulatus. Tick larvae are the first
      developmental stage to infest hosts, acquire infection and transmit pathogens
      that are transovarially transmitted and are exposed to extremely stressing
      conditions. In this study, we used a systems biology approach to get an insight
      into the mechanisms active in D. reticulatus unfed larvae, with special emphasis
      on stress response. PRINCIPAL FINDINGS: The results support the use of paired end
      RNA sequencing and proteomics informed by transcriptomics (PIT) for the analysis
      of transcriptomics and proteomics data, particularly for organisms such as D.
      reticulatus with little sequence information available. The results showed that
      metabolic and cellular processes involved in protein synthesis were the most
      active in D. reticulatus unfed larvae, suggesting that ticks are very active
      during this life stage. The stress response was activated in D. reticulatus unfed
      larvae and a Rickettsia sp. similar to R. raoultii was identified in these ticks.
      SIGNIFICANCE: The activation of stress responses in D. reticulatus unfed larvae
      likely counteracts the negative effect of temperature and other stress conditions
      such as Rickettsia infection and favors tick adaptation to environmental
      conditions to increase tick survival. These results show mechanisms that have
      evolved in D. reticulatus ticks to survive under stress conditions and suggest
      that these mechanisms are conserved across hard tick species. Targeting some of
      these proteins by vaccination may increase tick susceptibility to natural stress
      conditions, which in turn reduce tick survival and reproduction, thus reducing
      tick populations and vector capacity for tick-borne pathogens.

PMID- 24586876
TI  - A critical evaluation of microRNA biomarkers in non-neoplastic disease.
AB  - BACKGROUND: MicroRNAs (miRNAs) are small (~22-nt), stable RNAs that critically
      modulate post-transcriptional gene regulation. MicroRNAs can be found in the
      blood as components of serum, plasma and peripheral blood mononuclear cells
      (PBMCs). Many microRNAs have been reported to be specific biomarkers in a variety
      of non-neoplastic diseases. To date, no one has globally evaluated these proposed
      clinical biomarkers for general quality or disease specificity. We hypothesized
      that the cellular source of circulating microRNAs should correlate with cells
      involved in specific non-neoplastic disease processes. Appropriate cell
      expression data would inform on the quality and usefulness of each microRNA as a
      biomarker for specific diseases. We further hypothesized a useful clinical
      microRNA biomarker would have specificity to a single disease. METHODS AND
      FINDINGS: We identified 416 microRNA biomarkers, of which 192 were unique, in 104
      publications covering 57 diseases. One hundred and thirty-nine microRNAs (33%)
      represented biologically plausible biomarkers, corresponding to non-ubiquitous
      microRNAs expressed in disease-appropriate cell types. However, at a global
      level, many of these microRNAs were reported as "specific" biomarkers for two or
      more unrelated diseases with 6 microRNAs (miR-21, miR-16, miR-146a, miR-155, miR
      126 and miR-223) being reported as biomarkers for 9 or more distinct diseases.
      Other biomarkers corresponded to common patterns of cellular injury, such as the
      liver-specific microRNA, miR-122, which was elevated in a disparate set of
      diseases that injure the liver primarily or secondarily including hepatitis B,
      hepatitis C, sepsis, and myocardial infarction. CONCLUSIONS: Only a subset of
      reported blood-based microRNA biomarkers have specificity for a particular
      disease. The remainder of the reported non-neoplastic biomarkers are either
      biologically implausible, non-specific, or uninterpretable due to limitations of
      our current understanding of microRNA expression.

PMID- 24586877
TI  - Fearful gaze cueing: gaze direction and facial expression independently influence
      overt orienting responses in 12-month-olds.
AB  - Gaze direction cues and facial expressions have been shown to influence object
      processing in infants. For example, infants around 12 months of age utilize
      others' gaze directions and facial expressions to regulate their own behaviour
      toward an ambiguous target (i.e., social referencing). However, the mechanism by
      which social signals influence overt orienting in infants is unclear. The present
      study examined the effects of static gaze direction cues and facial expressions
      (neutral vs. fearful) on overt orienting using a gaze-cueing paradigm in 6- and
      12-month-old infants. Two experiments were conducted: in Experiment 1, a face
      with a leftward or rightward gaze direction was used as a cue, and a face with a
      forward gaze direction was added in Experiment 2. In both experiments, an effect
      of facial expression was found in 12-month-olds; no effect was found in 6-month
      olds. Twelve-month-old infants exhibited more rapid overt orienting in response
      to fearful expressions than neutral expressions, irrespective of gaze direction.
      These findings suggest that gaze direction information and facial expressions
      independently influence overt orienting in infants, and the effect of facial
      expression emerges earlier than that of static gaze direction. Implications for
      the development of gaze direction and facial expression processing systems are
      discussed. 

PMID- 24586878
TI  - Impacts of edaphic factors on communities of ammonia-oxidizing archaea, ammonia
      oxidizing bacteria and nitrification in tropical soils.
AB  - Nitrification is a key process in soil nitrogen (N) dynamics, but relatively
      little is known about it in tropical soils. In this study, we examined soils from
      Trinidad to determine the edaphic drivers affecting nitrification levels and
      community structure of ammonia-oxidizing bacteria (AOB) and ammonia-oxidizing
      archaea (AOA) in non-managed soils. The soils were naturally vegetated, ranged in
      texture from sands to clays and spanned pH 4 to 8. The AOA were detected by qPCR
      in all soils (ca. 10(5) to 10(6) copies archaeal amoA g(-1) soil), but AOB levels
      were low and bacterial amoA was infrequently detected. AOA abundance showed a
      significant negative correlation (p<0.001) with levels of soil organic carbon,
      clay and ammonium, but was not correlated to pH. Structures of AOA and AOB
      communities, as determined by amoA terminal restriction fragment (TRF) analysis,
      differed significantly between soils (p<0.001). Variation in AOA TRF profiles was
      best explained by ammonium-N and either Kjeldahl N or total N (p<0.001) while
      variation in AOB TRF profiles was best explained by phosphorus, bulk density and
      iron (p<0.01). In clone libraries, phylotypes of archaeal amoA (predominantly
      Nitrososphaera) and bacterial amoA (predominanatly Nitrosospira) differed between
      soils, but variation was not correlated with pH. Nitrification potential was
      positively correlated with clay content and pH (p<0.001), but not to AOA or AOB
      abundance or community structure. Collectively, the study showed that AOA and AOB
      communities were affected by differing sets of edaphic factors, notably that soil
      N characteristics were significant for AOA, but not AOB, and that pH was not a
      major driver for either community. Thus, the effect of pH on nitrification
      appeared to mainly reflect impacts on AOA or AOB activity, rather than selection
      for AOA or AOB phylotypes differing in nitrifying capacity. 

PMID- 24586879
TI  - Involvement of MIF in basement membrane damage in chronically UVB-exposed skin in
      mice.
AB  - Solar ultraviolet (UV) B radiation is known to induce matrix metalloproteinases
      (MMPs) that degrade collagen in the basement membrane. Macrophage migration
      inhibitory factor (MIF) is a pluripotent cytokine that plays an essential role in
      the pathophysiology of skin inflammation induced by UV irradiation. This study
      examined the effects of MIF on basement membrane damage following chronic UVB
      irradiation in mice. The back skin of MIF transgenic (Tg) and wild-type (WT) mice
      was exposed to UVB three times a week for 10 weeks. There was a decrease in
      intact protein levels of type IV collagen and increased basement membrane damage
      in the exposed skin of the MIF Tg mice compared to that observed in the WT mice.
      Moreover, the skin of the MIF Tg mice exhibited higher MIF, MMP-2 and MMP-9
      expression and protein levels than those observed in the WT mice. We also found
      that chronic UVB exposure in MIF Tg mice resulted in higher levels of neutrophil
      infiltration in the dermis compared with that observed in the WT mice. In vitro
      experiments revealed that MIF induced increases in the MMPs expression, including
      that of MMP-9 in keratinocytes and MMP-2 in fibroblasts. Cultured neutrophils
      also secreted MMP-9 stimulated by MIF. Therefore, MIF-mediated basement membrane
      damage occurs primarily through MMPs activation and neutrophil influx in murine
      skin following chronic UVB irradiation. 

PMID- 24586881
TI  - Estimates of forest biomass carbon storage inLiaoning Province of Northeast
      China: a review and assessment.
AB  - Accurate estimates of forest carbon storage and changes in storage capacity are
      critical for scientific assessment of the effects of forest management on the
      role of forests as carbon sinks. Up to now, several studies reported forest
      biomass carbon (FBC) in Liaoning Province based on data from China's Continuous
      Forest Inventory, however, their accuracy were still not known. This study
      compared estimates of FBC in Liaoning Province derived from different methods. We
      found substantial variation in estimates of FBC storage for young and middle-age
      forests. For provincial forests with high proportions in these age classes, the
      continuous biomass expansion factor method (CBM) by forest type with age class is
      more accurate and therefore more appropriate for estimating forest biomass. Based
      on the above approach designed for this study, forests in Liaoning Province were
      found to be a carbon sink, with carbon stocks increasing from 63.0 TgC in 1980 to
      120.9 TgC in 2010, reflecting an annual increase of 1.9 TgC. The average carbon
      density of forest biomass in the province has increased from 26.2 Mg ha(-1) in
      1980 to 31.0 Mg ha(-1) in 2010. While the largest FBC occurred in middle-age
      forests, the average carbon density decreased in this age class during these
      three decades. The increase in forest carbon density resulted primarily from the
      increased area and carbon storage of mature forests. The relatively long age
      interval in each age class for slow-growing forest types increased the
      uncertainty of FBC estimates by CBM-forest type with age class, and further
      studies should devote more attention to the time span of age classes in
      establishing biomass expansion factors for use in CBM calculations. 

PMID- 24586880
TI  - Exon first nucleotide mutations in splicing: evaluation of in silico prediction
      tools.
AB  - Mutations in the first nucleotide of exons (E(+1)) mostly affect pre-mRNA
      splicing when found in AG-dependent 3' splice sites, whereas AG-independent
      splice sites are more resistant. The AG-dependency, however, may be difficult to
      assess just from primary sequence data as it depends on the quality of the
      polypyrimidine tract. For this reason, in silico prediction tools are commonly
      used to score 3' splice sites. In this study, we have assessed the ability of
      sequence features and in silico prediction tools to discriminate between the
      splicing-affecting and non-affecting E(+1) variants. For this purpose, we newly
      tested 16 substitutions in vitro and derived other variants from literature.
      Surprisingly, we found that in the presence of the substituting nucleotide, the
      quality of the polypyrimidine tract alone was not conclusive about its splicing
      fate. Rather, it was the identity of the substituting nucleotide that markedly
      influenced it. Among the computational tools tested, the best performance was
      achieved using the Maximum Entropy Model and Position-Specific Scoring Matrix. As
      a result of this study, we have now established preliminary discriminative cut
      off values showing sensitivity up to 95% and specificity up to 90%. This is
      expected to improve our ability to detect splicing-affecting variants in a
      clinical genetic setting. 

PMID- 24586882
TI  - Impact of antiretroviral therapy on renal function among HIV-infected Tanzanian
      adults: a retrospective cohort study.
AB  - BACKGROUND: Data regarding the outcomes of HIV-infected adults with baseline
      renal dysfunction who start antiretroviral therapy are conflicting. METHODS: We
      followed up a previously-published cohort of HIV-infected adult outpatients in
      northwest Tanzania who had high prevalence of renal dysfunction at the time of
      starting antiretroviral therapy (between November 2009 and February 2010).
      Patients had serum creatinine, proteinuria, microalbuminuria, and CD4(+) T-cell
      count measured at the time of antiretroviral therapy initiation and at follow-up.
      We used the adjusted Cockroft-Gault equation to calculate estimated glomerular
      filtration rates (eGFRs). RESULTS: In this cohort of 171 adults who had taken
      antiretroviral therapy for a median of two years, the prevalence of renal
      dysfunction (eGFR <90 mL/min/1.73 m(2)) decreased from 131/171 (76.6%) at the
      time of ART initiation to 50/171 (29.2%) at the time of follow-up (p<0.001).
      Moderate dysfunction (eGFR<60 mL/min/1.73 m(2)) decreased from 21.1% at
      antiretroviral therapy initiation to 1.1% at follow-up (p<0.001), as did the
      prevalence of microalbuminuria (72% to 44%, p<0.001). Use of tenofovir was not
      associated with renal dysfunction at follow-up. CONCLUSION: Mild and moderate
      renal dysfunction were common in this cohort of HIV-infected adults initiating
      antiretroviral therapy, and both significantly improved after a median follow-up
      time of 2 years. Our work supports the renal safety of antiretroviral therapy in
      African adults with mild-moderate renal dysfunction, suggesting that these
      regimens do not lead to renal damage in the majority of patients and that they
      may even improve renal function in patients with mild to moderate renal
      dysfunction.

PMID- 24586883
TI  - Actigraphic assessment of motor activity in acutely admitted inpatients with
      bipolar disorder.
AB  - INTRODUCTION: Mania is associated with increased activity, whereas psychomotor
      retardation is often found in bipolar depression. Actigraphy is a promising tool
      for monitoring phase shifts and changes following treatment in bipolar disorder.
      The aim of this study was to compare recordings of motor activity in mania,
      bipolar depression and healthy controls, using linear and nonlinear analytical
      methods. MATERIALS AND METHODS: Recordings from 18 acutely hospitalized
      inpatients with mania were compared to 12 recordings from bipolar depression
      inpatients and 28 healthy controls. 24-hour actigraphy recordings and 64-minute
      periods of continuous motor activity in the morning and evening were analyzed.
      Mean activity and several measures of variability and complexity were calculated.
      RESULTS: Patients with depression had a lower mean activity level compared to
      controls, but higher variability shown by increased standard deviation (SD) and
      root mean square successive difference (RMSSD) over 24 hours and in the active
      morning period. The patients with mania had lower first lag autocorrelation
      compared to controls, and Fourier analysis showed higher variance in the high
      frequency part of the spectrum corresponding to the period from 2-8 minutes. Both
      patient groups had a higher RMSSD/SD ratio compared to controls. In patients with
      mania we found an increased complexity of time series in the active morning
      period, compared to patients with depression. The findings in the patients with
      mania are similar to previous findings in patients with schizophrenia and healthy
      individuals treated with a glutamatergic antagonist. CONCLUSION: We have found
      distinctly different activity patterns in hospitalized patients with bipolar
      disorder in episodes of mania and depression, assessed by actigraphy and analyzed
      with linear and nonlinear mathematical methods, as well as clear differences
      between the patients and healthy comparison subjects.

PMID- 24586884
TI  - LAceP: lysine acetylation site prediction using logistic regression classifiers.
AB  - BACKGROUND: Lysine acetylation is a crucial type of protein post-translational
      modification, which is involved in many important cellular processes and serious
      diseases. However, identification of protein acetylated sites through traditional
      experiment methods is time-consuming and laborious. Those methods are not
      suitable to identify a large number of acetylated sites quickly. Therefore,
      computational methods are still very valuable to accelerate lysine acetylated
      site finding. RESULT: In this study, many biological characteristics of
      acetylated sites have been investigated, such as the amino acid sequence around
      the acetylated sites, the physicochemical property of the amino acids and the
      transition probability of adjacent amino acids. A logistic regression method was
      then utilized to integrate these information for generating a novel lysine
      acetylation prediction system named LAceP. When compared with existing methods,
      LAceP overwhelms most of state-of-the-art methods. Especially, LAceP has a more
      balanced prediction capability for positive and negative datasets. CONCLUSION:
      LAceP can integrate different biological features to predict lysine acetylation
      with high accuracy. An online web server is freely available at
      http://www.scbit.org/iPTM/.

PMID- 24586885
TI  - Oscillatory dynamics track motor performance improvement in human cortex.
AB  - Improving performance in motor skill acquisition is proposed to be supported by
      tuning of neural networks. To address this issue we investigated changes of phase
      amplitude cross-frequency coupling (paCFC) in neuronal networks during motor
      performance improvement. We recorded intracranially from subdural electrodes
      (electrocorticogram; ECoG) from 6 patients who learned 3 distinct motor tasks
      requiring coordination of finger movements with an external cue (serial response
      task, auditory motor coordination task, go/no-go). Performance improved in all
      subjects and all tasks during the first block and plateaued in subsequent blocks.
      Performance improvement was paralled by increasing neural changes in the trial-to
      trial paCFC between theta ([Formula: see text]; 4-8 Hz) phase and high gamma (HG;
      80-180 Hz) amplitude. Electrodes showing this covariation pattern (Pearson's r
      ranging up to .45) were located contralateral to the limb performing the task and
      were observed predominantly in motor brain regions. We observed stable paCFC when
      task performance asymptoted. Our results indicate that motor performance
      improvement is accompanied by adjustments in the dynamics and topology of
      neuronal network interactions in the [Formula: see text] and HG range. The
      location of the involved electrodes suggests that oscillatory dynamics in motor
      cortices support performance improvement with practice. 

PMID- 24586886
TI  - Ectopic expression of GsPPCK3 and SCMRP in Medicago sativa enhances plant
      alkaline stress tolerance and methionine content.
AB  - So far, it has been suggested that phosphoenolpyruvate carboxylases (PEPCs) and
      PEPC kinases (PPCKs) fulfill several important non-photosynthetic functions.
      However, the biological functions of soybean PPCKs, especially in alkali stress
      response, are not yet well known. In previous studies, we constructed a Glycine
      soja transcriptional profile, and identified three PPCK genes (GsPPCK1, GsPPCK2
      and GsPPCK3) as potential alkali stress responsive genes. In this study, we
      confirmed the induced expression of GsPPCK3 under alkali stress and investigated
      its tissue expression specificity by using quantitative real-time PCR analysis.
      Then we ectopically expressed GsPPCK3 in Medicago sativa and found that GsPPCK3
      overexpression improved plant alkali tolerance, as evidenced by lower levels of
      relative ion leakage and MDA content and higher levels of chlorophyll content and
      root activity. In this respect, we further co-transformed the GsPPCK3 and SCMRP
      genes into alfalfa, and demonstrated the increased alkali tolerance of GsPPCK3
      SCMRP transgenic lines. Further investigation revealed that GsPPCK3-SCMRP co
      overexpression promoted the PEPC activity, net photosynthetic rate and citric
      acid content of transgenic alfalfa under alkali stress. Moreover, we also
      observed the up-regulated expression of PEPC, CS (citrate synthase), H(+)-ATPase
      and NADP-ME genes in GsPPCK3-SCMRP transgenic alfalfa under alkali stress. As
      expected, we demonstrated that GsPPCK3-SCMRP transgenic lines displayed higher
      methionine content than wild type alfalfa. Taken together, results presented in
      this study supported the positive role of GsPPCK3 in plant response to alkali
      stress, and provided an effective way to simultaneously improve plant alkaline
      tolerance and methionine content, at least in legume crops. 

PMID- 24586887
TI  - Risk factors for methicillin resistant Staphylococcus aureus: a multi-laboratory
      study.
AB  - BACKGROUND: The present study aimed to investigate the dose response relationship
      between the prescriptions of antimicrobial agents and infection/colonization with
      methicillin resistant Staphylococcus aureus (MRSA) taking additional factors like
      stay in a health care facility into account. METHODS: Multi-centre retrospective
      study on a cohort of patients that underwent microbiological diagnostics in
      Belgium during 2005. The bacteriological results retrieved from 17 voluntary
      participating clinical laboratories were coupled with the individual
      antimicrobial consumption patterns (July 2004-December 2005) and other variables
      as provided by pooled data of health insurance funds. Multivariate analysis was
      used to identify risk factors for MRSA colonization/infection. RESULTS: A total
      of 6844 patients of which 17.5% died in the year 2005, were included in a
      logistic regression model. More than 97% of MRSA was associated with infection
      (clinical samples), and only a minority with screening/colonization (1.59%).
      Factors (95% CI) significantly (p<=<0.01) associated with MRSA in the final
      multivariate model were: admission to a long term care settings (2.79-4.46);
      prescription of antibiotics via a hospital pharmacy (1.30-2.01); age 55+ years
      (3.32-5.63); age 15-54 years (1.23-2.16); and consumption of antimicrobial agent
      per DDD (defined daily dose) (1.25-1.40). CONCLUSIONS: The data demonstrated a
      direct dose-response relationship between MRSA and consumption of antimicrobial
      agents at the individual patient level of 25-40% increased risk per every single
      day. In addition the study indicated an involvement of specific healthcare
      settings and age in MRSA status.

PMID- 24586888
TI  - Transcriptomic analysis of carboxylic acid challenge in Escherichia coli: beyond
      membrane damage.
AB  - Carboxylic acids are an attractive biorenewable chemical. Enormous progress has
      been made in engineering microbes for production of these compounds though titers
      remain lower than desired. Here we used transcriptome analysis of Escherichia
      coli during exogenous challenge with octanoic acid (C8) at pH 7.0 to probe
      mechanisms of toxicity. This analysis highlights the intracellular acidification
      and membrane damage caused by C8 challenge. Network component analysis identified
      transcription factors with altered activity including GadE, the activator of the
      glutamate-dependent acid resistance system (AR2) and Lrp, the amino acid
      biosynthesis regulator. The intracellular acidification was quantified during
      exogenous challenge, but was not observed in a carboxylic acid producing strain,
      though this may be due to lower titers than those used in our exogenous challenge
      studies. We developed a framework for predicting the proton motive force during
      adaptation to strong inorganic acids and carboxylic acids. This model predicts
      that inorganic acid challenge is mitigated by cation accumulation, but that
      carboxylic acid challenge inverts the proton motive force and requires anion
      accumulation. Utilization of native acid resistance systems was not useful in
      terms of supporting growth or alleviating intracellular acidification. AR2 was
      found to be non-functional, possibly due to membrane damage. We proposed that
      interaction of Lrp and C8 resulted in repression of amino acid biosynthesis.
      However, this hypothesis was not supported by perturbation of lrp expression or
      amino acid supplementation. E. coli strains were also engineered for altered
      cyclopropane fatty acid content in the membrane, which had a dramatic effect on
      membrane properties, though C8 tolerance was not increased. We conclude that
      achieving higher production titers requires circumventing the membrane damage. As
      higher titers are achieved, acidification may become problematic. 

PMID- 24586889
TI  - Spinal changes of a newly isolated neuropeptide endomorphin-2 concomitant with
      vincristine-induced allodynia.
AB  - Chemotherapy-induced neuropathic pain (CNP) is the major dose-limiting factor in
      cancer chemotherapy. However, the neural mechanisms underlying CNP remain
      unclear. There is increasing evidence implicating the involvement of spinal
      endomorphin-2 (EM2) in neuropathic pain. In this study, we used a vincristine
      evoked rat CNP model displaying mechanical allodynia and central sensitization,
      and observed a significant decrease in the expression of spinal EM2 in CNP. Also,
      while intrathecal administration of exogenous EM2 attenuated allodynia and
      central sensitization, the mu-opioid receptor antagonist beta-funaltrexamine
      facilitated these events. We found that the reduction in spinal EM2 was mediated
      by increased activity of dipeptidylpeptidase IV, possibly as a consequence of
      chemotherapy-induced oxidative stress. Taken together, our findings suggest that
      a decrease in spinal EM2 expression causes the loss of endogenous analgesia and
      leads to enhanced pain sensation in CNP. 

PMID- 24586890
TI  - Comprehensive behavioral analysis of cluster of differentiation 47 knockout mice.
AB  - Cluster of differentiation 47 (CD47) is a member of the immunoglobulin
      superfamily which functions as a ligand for the extracellular region of signal
      regulatory protein alpha (SIRPalpha), a protein which is abundantly expressed in
      the brain. Previous studies, including ours, have demonstrated that both CD47 and
      SIRPalpha fulfill various functions in the central nervous system (CNS), such as
      the modulation of synaptic transmission and neuronal cell survival. We previously
      reported that CD47 is involved in the regulation of depression-like behavior of
      mice in the forced swim test through its modulation of tyrosine phosphorylation
      of SIRPalpha. However, other potential behavioral functions of CD47 remain
      largely unknown. In this study, in an effort to further investigate functional
      roles of CD47 in the CNS, CD47 knockout (KO) mice and their wild-type littermates
      were subjected to a battery of behavioral tests. CD47 KO mice displayed decreased
      prepulse inhibition, while the startle response did not differ between genotypes.
      The mutants exhibited slightly but significantly decreased sociability and social
      novelty preference in Crawley's three-chamber social approach test, whereas in
      social interaction tests in which experimental and stimulus mice have direct
      contact with each other in a freely moving setting in a novel environment or home
      cage, there were no significant differences between the genotypes. While previous
      studies suggested that CD47 regulates fear memory in the inhibitory avoidance
      test in rodents, our CD47 KO mice exhibited normal fear and spatial memory in the
      fear conditioning and the Barnes maze tests, respectively. These findings suggest
      that CD47 is potentially involved in the regulation of sensorimotor gating and
      social behavior in mice. 

PMID- 24586891
TI  - Production and transfer of energy and information in Hamiltonian systems.
AB  - We present novel results that relate energy and information transfer with
      sensitivity to initial conditions in chaotic multi-dimensional Hamiltonian
      systems. We show the relation among Kolmogorov-Sinai entropy, Lyapunov exponents,
      and upper bounds for the Mutual Information Rate calculated in the Hamiltonian
      phase space and on bi-dimensional subspaces. Our main result is that the net
      amount of transfer from kinetic to potential energy per unit of time is a power
      law of the upper bound for the Mutual Information Rate between kinetic and
      potential energies, and also a power-law of the Kolmogorov-Sinai entropy.
      Therefore, transfer of energy is related with both transfer and production of
      information. However, the power-law nature of this relation means that a small
      increment of energy transferred leads to a relatively much larger increase of the
      information exchanged. Then, we propose an "experimental" implementation of a 1
      dimensional communication channel based on a Hamiltonian system, and calculate
      the actual rate with which information is exchanged between the first and last
      particle of the channel. Finally, a relation between our results and important
      quantities of thermodynamics is presented. 

PMID- 24586892
TI  - Noroviral p-particles as an in vitro model to assess the interactions of
      noroviruses with probiotics.
AB  - Noroviruses (NoVs) are the main etiologic agents of acute epidemic
      gastroenteritis and probiotic bacteria have been reported to exert a positive
      effect on viral diarrhea. The protruding (P) domain from NoVs VP1 capsid protein
      has the ability to assemble into the so-called P-particles, which retain the
      binding ability to host receptors. We purified the P-domains from NoVs genotypes
      GI.1 and GII.4 as 6X(His)-tagged proteins and determined that, similar to native
      domains, they were structured into P-particles that were functional in the
      recognition of the specific glycoconjugated receptors, as established by surface
      plasmon resonance experiments. We showed that several lactic acid bacteria
      (probiotic and non-probiotic) and a Gram-negative probiotic strain have the
      ability to bind P-particles on their surfaces irrespective of their probiotic
      status. The binding of P-particles (GI.1) to HT-29 cells in the presence of
      selected strains showed that bacteria can inhibit P-particle attachment in
      competitive exclusion experiments. However, pre-treatment of cells with bacteria
      or adding bacteria to cells with already attached P-particles enhanced the
      retention of the particles. Although direct viral binding and blocking of viral
      receptors have been postulated as mechanisms of protection against viral
      infection by probiotic bacteria, these results highlight the need for a careful
      evaluation of this hypothesis. The work presented here investigates for the first
      time the probiotic-NoVs-host interactions and points up the NoVs P-particles as
      useful tools to overcome the absence of in vitro cellular models to propagate
      these viruses. 

PMID- 24586894
TI  - Influence of different plant species on methane emissions from soil in a restored
      Swiss wetland.
AB  - Plants are a major factor influencing methane emissions from wetlands, along with
      environmental parameters such as water table, temperature, pH, nutrients and soil
      carbon substrate. We conducted a field experiment to study how different plant
      species influence methane emissions from a wetland in Switzerland. The top 0.5 m
      of soil at this site had been removed five years earlier, leaving a substrate
      with very low methanogenic activity. We found a sixfold difference among plant
      species in their effect on methane emission rates: Molinia caerulea and
      Lysimachia vulgaris caused low emission rates, whereas Senecio paludosus, Carex
      flava, Juncus effusus and Typha latifolia caused relatively high rates. Centaurea
      jacea, Iris sibirica, and Carex davalliana caused intermediate rates. However, we
      found no effect of either plant biomass or plant functional groups--based on life
      form or productivity of the habitat--upon methane emission. Emissions were much
      lower than those usually reported in temperate wetlands, which we attribute to
      reduced concentrations of labile carbon following topsoil removal. Thus, unlike
      most wetland sites, methane production in this site was probably fuelled chiefly
      by root exudation from living plants and from root decay. We conclude that in
      most wetlands, where concentrations of labile carbon are much higher, these
      sources account for only a small proportion of the methane emitted. Our study
      confirms that plant species composition does influence methane emission from
      wetlands, and should be considered when developing measures to mitigate the
      greenhouse gas emissions.

PMID- 24586893
TI  - Wat1/pop3, a conserved WD repeat containing protein acts synergistically with
      checkpoint kinase Chk1 to maintain genome ploidy in fission yeast S. pombe.
AB  - Aberrant chromosome segregation defects can lead to aneuploidy, a common
      characteristic of human solid tumors. Aneuploidy is generated due to defects in
      the mitotic spindle or due to inefficient mitotic checkpoint response. We have
      isolated a novel mutant allele of wat1, a WD repeat containing protein that
      exhibits conditional synthetic lethality with chk1 knock out. We observed only a
      marginal decrease in the level of alpha tubulin protein level in wat1-17 mutants
      after prolong exposure at semi permissive temperature. Interestingly the protein
      level of alpha-tubulin was reduced in the chk1Delta wat1-17 double mutant at 18
      degrees C with defective microtubule structure. Consistent with loss of
      microtubule structure in the chk1 deletion background, the double mutant of wat1
      17 chk1Delta was hypersensitive to the microtubule destabilizing agent TBZ
      suggesting severe defects in microtubule integrity in wat1-17 mutant in the
      absence of Chk1. Combination of wat1-17 with the chk1 deletion also aggravates
      the defects in the maintenance of genome ploidy. The mutation in wat1-17 was
      mapped to Cys 233 that was changed to tyrosine. Based on the molecular modeling
      studies, we hypothesize that the substitution of the bulky Tyr residue at Cys233
      position in wat1-17 mutant results in conformational changes. This in turn can
      affect its intercations with other interacting partners and perturb the overall
      functions of the Wat1 protein. 

PMID- 24586895
TI  - Adjustments of speed and path when avoiding collisions with another pedestrian.
AB  - When walking in open space, collision avoidance with other pedestrians is a
      process that successfully takes place many times. To pass another pedestrian (an
      interferer) walking direction, walking speed or both can be adjusted. Currently,
      the literature is not yet conclusive of how humans adjust these two parameters in
      the presence of an interferer. This impedes the development of models predicting
      general obstacle avoidance strategies in humans' walking behavior. The aim of
      this study was to investigate the adjustments of path and speed when a pedestrian
      is crossing a non-reactive human interferer at different angles and speeds, and
      to compare the results to general model predictions. To do so, we designed an
      experiment where a pedestrian walked a 12 m distance to reach a goal position.
      The task was designed in such a way that collision with an interferer would
      always occur if the pedestrian would not apply a correction of movement path or
      speed. Results revealed a strong dependence of path and speed adjustments on
      crossing angle and walking speed, suggesting local planning of the collision
      avoidance strategy. Crossing at acute angles (i.e. 45 degrees  and 90 degrees )
      seems to require more complex collision avoidance strategies involving both path
      and speed adjustments than crossing at obtuse angles, where only path adjustments
      were observed. Overall, the results were incompatible with predictions from
      existing models of locomotor collision avoidance. The observed initiations of
      both adjustments suggest a collision avoidance strategy that is temporally
      controlled. The present study provides a comprehensive picture of human collision
      avoidance strategies in walking, which can be used to evaluate and adjust
      existing pedestrian dynamics models, or serve as an empirical basis to develop
      new models. 

PMID- 24586896
TI  - Anthropometrics and body composition by dual energy X-ray in children of obese
      women: a follow-up of a randomized controlled trial (the Lifestyle in Pregnancy
      and Offspring [LiPO] study).
AB  - OBJECTIVE: In obese women, 1) to assess whether lower gestational weight gain
      (GWG) during pregnancy in the lifestyle intervention group of a randomized
      controlled trial (RCT) resulted in differences in offspring anthropometrics and
      body composition, and 2) to compare offspring outcomes to a reference group of
      children born to women with a normal Body Mass Index (BMI). RESEARCH DESIGN AND
      METHODS: The LiPO (Lifestyle in Pregnancy and Offspring) study was an offspring
      follow-up of a RCT with 360 obese pregnant women with a lifestyle intervention
      during pregnancy including dietary advice, coaching and exercise. The trial was
      completed by 301 women who were eligible for follow-up. In addition, to the
      children from the RCT, a group of children born to women with a normal BMI were
      included as a reference group. At 2.8 (range 2.5-3.2) years, anthropometrics were
      measured in 157 children of the RCT mothers and in 97 reference group children
      with Body Mass Index (BMI) Z-score as a primary outcome. Body composition was
      estimated by Dual Energy X-ray (DEXA) in 123 successful scans out of 147 (84%).
      RESULTS: No differences between randomized groups were seen in mean (95% C.I.)
      BMI Z-score (intervention group 0.06 [-0.17; 0.29] vs. controls -0.18 [-0.43;
      0.05]), in the percentage of overweight or obese children (10.9% vs. 6.7%), in
      other anthropometrics, or in body composition values by DEXA. Outcomes between
      children from the RCT and the reference group children were not significantly
      different. CONCLUSIONS: The RCT with lifestyle intervention in obese pregnant
      women did not result in any detectable effect on offspring anthropometrics or
      body composition by DEXA at 2.8 years of age. This may reflect the limited
      difference in GWG between intervention and control groups. Offspring of obese
      mothers from the RCT were comparable to offspring of mothers with a normal BMI.

PMID- 24586897
TI  - Improving adherence and clinical outcomes in self-guided internet treatment for
      anxiety and depression: a 12-month follow-up of a randomised controlled trial.
AB  - BACKGROUND: A recent paper reported the outcomes of a study examining a new self
      guided internet-delivered treatment, the Wellbeing Course, for symptoms of
      anxiety or depression. This study found the intervention resulted in significant
      symptom reductions. It also found that automated emails increased treatment
      completion and clinical improvements in a subsample with elevated anxiety and
      depression. AIMS: To examine the clinical outcomes and the effect of automated
      emails at 12 months post-treatment. METHOD: Participants, who were randomly
      allocated to a Treatment Plus Automated Emails Group (TEG; n = 100), a standard
      Treatment Group (TG; n = 106) or delayed-treatment Waitlist Control Group
      (Control; n = 51), were followed up at 12 months post-treatment. Eighty-one
      percent, 78% and 87% of participants in the TEG, TG and treated Waitlist Control
      Group provided symptom data at 12-month follow-up, respectively. The primary
      outcome measures were the Patient Health Questionnaire-9 Item Scale (PHQ-9) and
      the Generalized Anxiety Disorder-7 Item Scale (GAD-7). RESULTS: Significant
      improvements in symptoms of anxiety and depression were observed over time in
      both the TEG and TG (Fs >69, ps <.001) these were sustained from post-treatment
      to 12-month follow-up (ps >.05), and were associated with large effect sizes. No
      statistically significant differences in symptoms were found between the TEG and
      TG at post-treatment, 3-month or 12-month follow-up. Previously reported symptom
      differences between TEG and TG participants with comorbid symptoms were no longer
      present at 12-month follow-up (ps >.70). CONCLUSIONS: The overall benefits of the
      Wellbeing Course were sustained at 12-month follow-up. Although automated emails
      facilitated Course completion and reductions in symptoms for participants with
      comorbid anxiety and depression from pre-post treatment, these differences were
      no longer observed at 12-month follow-up. The results indicate that automated
      emails promote more rapid treatment response for people with elevated and
      comorbid symptoms, but may not improve longer term outcomes. TRIAL REGISTRATION:
      Australian and New Zealand Clinical Trials Registry ACTRN12610001058066.

PMID- 24586898
TI  - The direction of stretch-induced cell and stress fiber orientation depends on
      collagen matrix stress.
AB  - Cell structure depends on both matrix strain and stiffness, but their interactive
      effects are poorly understood. We investigated the interactive roles of matrix
      properties and stretching patterns on cell structure by uniaxially stretching
      U2OS cells expressing GFP-actin on silicone rubber sheets supporting either a
      surface-adsorbed coating or thick hydrogel of type-I collagen. Cells and their
      actin stress fibers oriented perpendicular to the direction of cyclic stretch on
      collagen-coated sheets, but oriented parallel to the stretch direction on
      collagen gels. There was significant alignment parallel to the direction of a
      steady increase in stretch for cells on collagen gels, while cells on collagen
      coated sheets did not align in any direction. The extent of alignment was
      dependent on both strain rate and duration. Stretch-induced alignment on collagen
      gels was blocked by the myosin light-chain kinase inhibitor ML7, but not by the
      Rho-kinase inhibitor Y27632. We propose that active orientation of the actin
      cytoskeleton perpendicular and parallel to direction of stretch on stiff and soft
      substrates, respectively, are responses that tend to maintain intracellular
      tension at an optimal level. Further, our results indicate that cells can align
      along directions of matrix stress without collagen fibril alignment, indicating
      that matrix stress can directly regulate cell morphology. 

PMID- 24586899
TI  - Monitoring what governments "give for" and "spend on" vaccine procurement:
      Vaccine Procurement Assistance and Vaccine Procurement Baseline.
AB  - BACKGROUND: The Global Vaccine Action Plan will require, inter alia, the
      mobilization of financial resources from donors and national governments - both
      rich and poor. Vaccine Procurement Assistance (VPA) and Vaccine Procurement
      Baseline (VPB) are two metrics that could measure government performance and
      track resources in this arena. VPA is proposed as a new subcategory of Official
      Development Assistance (ODA) given for the procurement of vaccines and VPB is a
      previously suggested measure of the share of Gross Domestic Product (GDP) that
      governments spend on their own vaccine procurement. OBJECTIVE: To determine
      realistic targets for VPA and VPB. METHODS: Organization for Economic Co
      Operation and Development (OECD) and World Bank data for 2009 were analyzed to
      determine the proportions of bilateral ODA from the 23 Development Assistance
      Committee (DAC) countries disbursed (as % of GDP in current US$) for infectious
      disease control. DAC country contributions to the GAVI Alliance for 2009 were
      assessed as a measure of multilateral donor support for vaccines and immunization
      programs. FINDINGS: In 2009, total DAC bilateral ODA was 0.16% of global GDP and
      0.25% of DAC GDP. As a percentage of GDP, Norway (0.013%) and United Kingdom
      (0.0085%) disbursed the greatest proportion of bilateral ODA for infectious
      disease control, and Norway (0.024%) and Canada (0.008%) made the greatest
      contributions to the GAVI Alliance. In 2009 0.02% of DAC GDP was US$7.61 billion
      and 0.02% of the GDP of the poorest 117 countries was US$2.88 billion.
      CONCLUSIONS: Adopting 0.02% GDP as minimum targets for both VPA and VPB is based
      on realistic estimates of what both developed and developing countries should
      spend, and can afford to spend, to jointly ensure procurement of vaccines
      recommended by national and global bodies. New OECD purpose codes are needed to
      specifically track ODA disbursed for a) vaccine procurement; and b) immunization
      programs.

PMID- 24586900
TI  - Human adipose tissue-derived stromal/stem cells promote migration and early
      metastasis of triple negative breast cancer xenografts.
AB  - BACKGROUND: Fat grafting is used to restore breast defects after surgical
      resection of breast tumors. Supplementing fat grafts with adipose tissue-derived
      stromal/stem cells (ASCs) is proposed to improve the regenerative/restorative
      ability of the graft and retention. However, long term safety for ASC grafting in
      proximity of residual breast cancer cells is unknown. The objective of this study
      was to determine the impact of human ASCs derived from abdominal lipoaspirates of
      three donors, on a human breast cancer model that exhibits early metastasis.
      METHODOLOGY/PRINCIPAL FINDINGS: Human MDA-MB-231 breast cancer cells represents
      "triple negative" breast cancer that exhibits early micrometastasis to multiple
      mouse organs [1]. Human ASCs were derived from abdominal adipose tissue from
      three healthy female donors. Indirect co-culture of MDA-MB-231 cells with ASCs,
      as well as direct co-culture demonstrated that ASCs had no effect on MDA-MB-231
      growth. Indirect co-culture, and ASC conditioned medium (CM) stimulated migration
      of MDA-MB-231 cells. ASC/RFP cells from two donors co-injected with MDA-MB
      231/GFP cells exhibited a donor effect for stimulation of primary tumor
      xenografts. Both ASC donors stimulated metastasis. ASC/RFP cells were viable, and
      integrated with MDA-MB-231/GFP cells in the tumor. Tumors from the co-injection
      group of one ASC donor exhibited elevated vimentin, matrix metalloproteinase-9
      (MMP-9), IL-8, VEGF and microvessel density. The co-injection group exhibited
      visible metastases to the lung/liver and enlarged spleen not evident in mice
      injected with MDA-MB-231/GFP alone. Quantitation of the total area of GFP
      fluorescence and human chromosome 17 DNA in mouse organs, H&E stained paraffin
      sections and fluorescent microscopy confirmed multi-focal metastases to
      lung/liver/spleen in the co-injection group without evidence of ASC/RFP cells.
      CONCLUSIONS: Human ASCs derived from abdominal lipoaspirates of two donors
      stimulated metastasis of MDA-MB-231 breast tumor xenografts to multiple mouse
      organs. MDA-MB-231 tumors co-injected with ASCs from one donor exhibited partial
      EMT, expression of MMP-9, and increased angiogenesis.

PMID- 24586902
TI  - Internet use and its impact on engagement in leisure activities in China.
AB  - INTRODUCTION: Internet use has become an increasingly common leisure time
      activity among Chinese citizens. The association between Internet use and
      engagement in leisure activities is especially unclear among China population.
      This study aims to investigate Internet usage and to determine whether active
      Internet use is a marker for low or high levels of leisure time activities.
      METHODS/PRINCIPAL FINDINGS: With the use of a face-to-face structured
      questionnaire interview, a total of 2,400 respondents who met all screening
      requirements were surveyed to answer the questions in eight major cities in
      China. 66.2% (n = 1,589) of all respondents were identified as Internet users. Of
      these Internet users, 30.0%, 24.1%, 26.4%, and 19.6% were clustered as
      "informative or instrumental users," "entertainment users," "communication
      users," and "advanced users," respectively. Regarding time spent on Internet use
      in leisure time, more than 96% reported going online in non-work situations, and
      26.2% (n = 416) were classified as "heavy Internet users." A logistic regression
      analysis revealed that there were significant differences in some leisure
      activities between non-Internet users and Internet users, with an observed one
      unit increase in the leisure time dependence category increasing the probability
      of engaging in mental or social activities. In contrast, Internet users were less
      engaged in physical exercise-related activities. In addition, advanced Internet
      users were generally more active in leisure time activities than non-Internet
      users and other types of users. CONCLUSION/SIGNIFICANCE: Internet use is one of
      very common leisure activities in Chinese citizens, and age, gender, income, and
      education are the key factors affecting Internet access. According to different
      types of leisure activities, Internet usage has different impacts on leisure
      activity engagement. High Internet dependence has no significant negative
      influence on engagement in mental or social leisure activities, but this group
      respondent tended to be less engaged in physical activities.

PMID- 24586901
TI  - Highly immunoreactive IgG antibodies directed against a set of twenty human
      proteins in the sera of patients with amyotrophic lateral sclerosis identified by
      protein array.
AB  - Amyotrophic lateral sclerosis (ALS), the most common adult-onset motor neuron
      disorder, is characterized by the progressive and selective loss of upper and
      lower motor neurons. Diagnosis of this disorder is based on clinical assessment,
      and the average survival time is less than 3 years. Injections of IgG from ALS
      patients into mice are known to specifically mark motor neurons. Moreover, IgG
      has been found in upper and lower motor neurons in ALS patients. These results
      led us to perform a case-control study using human protein microarrays to
      identify the antibody profiles of serum samples from 20 ALS patients and 20
      healthy controls. We demonstrated high levels of 20 IgG antibodies that
      distinguished the patients from the controls. These findings suggest that a panel
      of antibodies may serve as a potential diagnostic biomarker for ALS. 

PMID- 24586905
TI  - Personal traits underlying environmental preferences: a discrete choice
      experiment.
AB  - Personality plays a role in human behavior, and thus can influence consumer
      decisions on environmental goods and services. This paper analyses the influence
      of the big five personality dimensions (extraversion, agreeableness,
      conscientiousness, neuroticism and openness) in a discrete choice experiment
      dealing with preferences for the development of an environmental program for
      forest management in Spain. For this purpose, a reduced version of the Big Five
      Inventory survey (the BFI-10) is implemented. Results show a positive effect of
      openness and extraversion and a negative effect of agreeableness and neuroticism
      in consumers' preferences for this environmental program. Moreover, results from
      a latent class model show that personal traits help to explain preference
      heterogeneity. 

PMID- 24586903
TI  - Serum and glucocorticoid-inducible kinase1 increases plasma membrane wt-CFTR in
      human airway epithelial cells by inhibiting its endocytic retrieval.
AB  - BACKGROUND: Chloride (Cl) secretion by the Cystic Fibrosis Transmembrane
      Conductance Regulator (CFTR) located in the apical membrane of respiratory
      epithelial cells plays a critical role in maintenance of the airway surface
      liquid and mucociliary clearance of pathogens. Previously, we and others have
      shown that the serum and glucocorticoid-inducible kinase-1 (SGK1) increases wild
      type CFTR (wt-CFTR) mediated Cl transport in Xenopus oocytes by increasing the
      amount of wt-CFTR protein in the plasma membrane. However, the effect of SGK1 on
      the membrane abundance of wt-CFTR in airway epithelial cells has not been
      examined, and the mechanism whereby SGK1 increases membrane wt-CFTR has also not
      been examined. Thus, the goal of this study was to elucidate the mechanism
      whereby SGK1 regulates the membrane abundance of wt-CFTR in human airway
      epithelial cells. METHODS AND RESULTS: We report that elevated levels of SGK1,
      induced by dexamethasone, increase plasma membrane abundance of wt-CFTR.
      Reduction of SGK1 expression by siRNA (siSGK1) and inhibition of SGK1 activity by
      the SGK inhibitor GSK 650394 abrogated the ability of dexamethasone to increase
      plasma membrane wt-CFTR. Overexpression of a constitutively active SGK1 (SGK1
      S422D) increased plasma membrane abundance of wt-CFTR. To understand the
      mechanism whereby SGK1 increased plasma membrane wt-CFTR, we examined the effects
      of siSGK1 and SGK1-S442D on the endocytic retrieval of wt-CFTR. While siSGK1
      increased wt-CFTR endocytosis, SGK1-S442D inhibited CFTR endocytosis. Neither
      siSGK1 nor SGK1-S442D altered the recycling of endocytosed wt-CFTR back to the
      plasma membrane. By contrast, SGK1 increased the endocytosis of the epidermal
      growth factor receptor (EGFR). CONCLUSION: This study demonstrates for the first
      time that SGK1 selectively increases wt-CFTR in the plasma membrane of human
      airway epithelia cells by inhibiting its endocytic retrieval from the membrane.

PMID- 24586906
TI  - Disruption of Fyn SH3 domain interaction with a proline-rich motif in liver
      kinase B1 results in activation of AMP-activated protein kinase.
AB  - Fyn-deficient mice display increased AMP-activated Protein Kinase (AMPK) activity
      as a result of Fyn-dependent regulation of Liver Kinase B1 (LKB1) in skeletal
      muscle. Mutation of Fyn-specific tyrosine sites in LKB1 results in LKB1 export
      into the cytoplasm and increased AMPK activation site phosphorylation. This study
      characterizes the structural elements responsible for the physical interaction
      between Fyn and LKB1. Effects of point mutations in the Fyn SH2/SH3 domains and
      in the LKB1 proline-rich motif on 1) Fyn and LKB1 binding, 2) LKB1 subcellular
      localization and 3) AMPK phosphorylation were investigated in C2C12 muscle cells.
      Additionally, novel LKB1 proline-rich motif mimicking cell permeable peptides
      were generated to disrupt Fyn/LKB1 binding and investigate the consequences on
      AMPK activity in both C2C12 cells and mouse skeletal muscle. Mutation of either
      Fyn SH3 domain or the proline-rich motif of LKB1 resulted in the disruption of
      Fyn/LKB1 binding, re-localization of 70% of LKB1 signal in the cytoplasm and a 2
      fold increase in AMPK phosphorylation. In vivo disruption of the Fyn/LKB1
      interaction using LKB1 proline-rich motif mimicking cell permeable peptides
      recapitulated Fyn pharmacological inhibition. We have pinpointed the structural
      elements within Fyn and LKB1 that are responsible for their binding,
      demonstrating the functionality of this interaction in regulating AMPK activity. 

PMID- 24586904
TI  - Methods to quantify soft tissue-based cranial growth and treatment outcomes in
      children: a systematic review.
AB  - CONTEXT: Longitudinal assessment of cranial dimensions of growing children
      provides healthcare professionals with information about normal and deviating
      growth as well as treatment outcome. OBJECTIVE: To give an overview of soft
      tissue-based methods for quantitative longitudinal assessment of cranial
      dimensions in children until age 6 years and to assess the reliability of these
      methods in studies with good methodological quality. DATA SOURCE: PubMed, EMBASE,
      Cochrane Library, Web of Science, Scopus, and CINAHL were searched. A manual
      search was performed to check for additional relevant studies. STUDY SELECTION:
      Primary publications on facial growth and treatment outcomes in children younger
      than age 6 years were included. DATA EXTRACTION: Independent data extraction was
      performed by two observers. A quality assessment instrument was used to determine
      methodological quality. Methods used in studies with good methodological quality
      were assessed for reliability expressed as the magnitude of the measurement error
      and the correlation coefficient between repeated measurements. RESULTS: In total,
      165 studies were included, forming three groups of methods: head circumference
      anthropometry, direct anthropometry, and 2D photography and 3D imaging techniques
      (surface laser scanning and stereophotogrammetry). In general, the measurement
      error was below 2 mm, and correlation coefficients were very good. CONCLUSION:
      Various methods for measuring cranial dimensions have shown to be reliable.
      Stereophotogrammetry is the most versatile method for quantitative longitudinal
      assessment of cranial dimensions and shapes in children. However, direct
      anthropometry continues to be the best method for routine clinical assessments of
      linear cranial dimensions in growing children until age 6 years.

PMID- 24586907
TI  - Matrix metalloproteinase (MMP)-9 in cancer-associated fibroblasts (CAFs) is
      suppressed by omega-3 polyunsaturated fatty acids in vitro and in vivo.
AB  - Cancer associated fibroblasts (CAFs) are responsible for tumor growth,
      angiogenesis, invasion, and metastasis. Matrix metalloproteinase (MMP)-9 secreted
      from cancer stroma populated by CAFs is a prerequisite for cancer angiogenesis
      and metastasis. Omega-3 polyunsaturated fatty acids (omega-3 PUFA) have been
      reported to have anti-tumor effects on diverse types of malignancies. Fat-1 mice,
      which can convert omega-6 to omega-3 PUFA independent of diet, are useful to
      investigate the functions of endogenous omega-3 PUFA. To examine the effect of
      omega-3 PUFA on tumorigenesis, TC-1 cells, a murine epithelial cell line
      immortalized by human papillomavirus (HPV) oncogenes, were injected
      subcutaneously into fat-1 or wild type mice. Tumor growth and angiogenesis of the
      TC-1 tumor were significantly suppressed in fat-1 compared to wild type mice.
      cDNA microarray of the tumors derived from fat-1 and wild type mice revealed that
      MMP-9 is downregulated in fat-1 mice. Immunohistochemical study demonstrated
      immunoreactivity for MMP-9 in the tumor stromal fibroblasts was diffusely
      positive in wild type whereas focal in fat-1 mice. MMP-9 was expressed in primary
      cultured fibroblasts isolated from fat-1 and wild type mice but was not expressed
      in TC-1 cells. Co-culture of fibroblasts with TC-1 cells enhanced the expression
      and the proteinase activity of MMP-9, although the protease activity of MMP-9 in
      fat-1-derived fibroblasts was lower than that in wild type fibroblasts. Our data
      suggests that omega-3 PUFAs suppress MMP-9 induction and tumor angiogenesis.
      These findings may provide insight into mechanisms by which omega-3 PUFAs exert
      anti-tumor effects by modulating tumor microenvironment. 

PMID- 24586908
TI  - Comparative proteomics and expression analysis of five genes in Epicauta
      chinensis larvae from the first to fifth instar.
AB  - Blister beetle is an important insect model for both medicinal and pure research.
      Previous research has mainly focused on its biology and biochemistry, but very
      little data is yet available in the molecular biology. This study uses
      differential proteomics technology to analyze the soluble proteins extracted from
      each of the 5 instars larvae of Epicauta chinensis. 42 of the differentially
      expressed proteins were identified successfully by MALDI-TOF/TOF-MS. Some of
      these proteins' function and their expression profiles are analyzed. Our analysis
      revealed dynamics regulation of the following proteins: Axin-like protein pry-1
      (APR-1), dihydrolipoyl dehydrogenase (DLD), vitellogenin (Vg) and lysozyme C (Lmz
      S). APR-1 negatively regulates the Wnt signaling pathway. Its overexpression
      could result in embryo, leg, eye and ovary ectopica or malformation. DLD
      catalyzes the pyruvate into acetyl-CoA, the latter is the starting material of
      juvenile hormone (JH) and ipsdienol biosynthesis through the MVA pathway in
      insects. While Vg synthesis can be regulated by JH and stimulated by food
      factors. So DLD may affect the synthesis of JH, ipsdienol and Vg indirectly. The
      activity of lysozyme is an indicator of the immunity. Nutrition/food should be
      taken into account for its potential role during the development of larva in the
      future. Among the five genes and their corresponding proteins' expression, only
      hsc70 gene showed a good correspondence with the protein level. This reflects the
      fluctuating relationship between mRNA and protein levels. 

PMID- 24586909
TI  - The standard, intervention measures and health risk for high water iodine areas.
AB  - Our study aims to clarify the population nutrient status in locations with
      different levels of iodine in the water in China; to choose effective
      measurements of water improvement(finding other drinking water source of iodine
      not excess) or non-iodised salt supply or combinations thereof; to classify the
      areas of elevated water iodine levels and the areas with endemic goiter; and to
      evaluate the risk factors of water iodine excess on pregnant women, lactating
      women and the overall population of women. From Henan, Hebei, Shandong and Shanxi
      province of China, for each of 50 ~ 99 ug/L, 100 ~ 149 ug/L, 150 ~ 299 ug/L, and
      >= 300 ug/L water iodine level, three villages were selected respectively.
      Students of 6-12 years old and pregnant were sampled from villages of each water
      iodine level of each province, excluded iodized salt consumer. Then the
      children's goiter volume, the children and pregnant's urinary iodine and water
      iodine were tested. In addition, blood samples were collected from pregnant
      women, lactating women and other women of reproductive age for each water iodine
      level in the Shanxi Province for thyroid function tests. These indicators should
      be matched for each person. When the water iodine exceeds 100 ug/L; the iodine
      nutrient of children are iodine excessive, and are adequate or more than adequate
      for the pregnant women. It is reasonable to define elevated water iodine areas as
      locations where the water iodine levels exceed 100 ug/L. The supply of non
      iodised salt alone cannot ensure adequate iodine nutrition of the residents, and
      water improvement must be adopted, as well. Iodine excess increases the risk of
      certain thyroid diseases in women from one- to eightfold.

PMID- 24586910
TI  - Pre-treatment ferritin level and alveolar-arterial oxygen gradient can predict
      mortality rate due to acute/subacute interstitial pneumonia in dermatomyositis
      treated by cyclosporine a/glucocorticosteroid combination therapy: a case control
      study [corrected].
AB  - BACKGROUND: Acute/subacute interstitial pneumonia in dermatomyositis (DM-A/SIP)
      is a disease associated with a poor prognosis that resists treatment with
      glucocorticosteroids (GC) and progresses rapidly in a period of weeks to months
      to death. We retrospectively studied outcomes, prognostic factors, and their
      relations with survival rate in patients with DM-A/SIP treated with early
      cyclosporine A (CSA)/GC combination therapy and 2-hour postdose blood
      concentration monitoring. METHODS: This study comprised 32 DM-A/SIP patients who
      were simultaneously treated with CSA and prednisolone. Clinical and laboratory
      findings were compared between those who died due to DM-A/SIP and those surviving
      24 weeks after beginning of therapy. Prognostic factors were extracted, and their
      relations with the survival rate were evaluated. RESULTS: Of the 32 DM-A/SIP
      patients, 25 survived, 5 died of DM-A/SIP, and 2 died of infections. In those who
      died due to DM-A/SIP, ferritin level and the alveolar-arterial oxygen gradient
      were significantly increased compared with the survivors (P<0.001 and P = 0.002,
      respectively). Multivariate analyses showed that ferritin and alveolar-arterial
      oxygen gradient were independent prognostic factors of poor outcome. The survival
      rate 24 weeks after beginning of treatment was significantly lower in those with
      a ferritin level of >= 600 ng/ml and alveolar-arterial oxygen gradient of >= 45
      Torr (P<0.001 and P<0.001, respectively). All patients with both prognostic
      factors died, and the outcome was significantly poorer in these patients than in
      those with one or neither of the prognostic factors (P<0.001). CONCLUSIONS: We
      identified pre-treatment high serum ferritin level and high alveolar-arterial
      oxygen gradient as poor prognostic factors in DM-A/SIP patients undergoing early
      CSA/GC combination therapy and showed that the outcomes were poor in patients
      with both factors.

PMID- 24586912
TI  - Safety, tolerability, and immunogenicity of the novel antituberculous vaccine
      RUTI: randomized, placebo-controlled phase II clinical trial in patients with
      latent tuberculosis infection.
AB  - OBJECTIVES: To evaluate the safety, tolerability and immunogenicity of three
      different doses (5, 25 and 50 ug) of the novel antituberculous vaccine RUTI
      compared to placebo in subjects with latent tuberculosis infection. METHODS AND
      FINDINGS: Double-blind, randomized, placebo-controlled Phase II Clinical Trial
      (95 patients randomized). Three different RUTI doses and placebo were tested,
      randomized both in HIV-positive (n = 47) and HIV-negative subjects (n = 48),
      after completion of one month isoniazid (INH) pre-vaccination. Each subject
      received two vaccine administrations, 28 Days apart. Five patients withdrew and
      90 patients completed the study. Assessment of safety showed no deaths during
      study. Two subjects had serious adverse events one had a retinal detachment while
      taking INH and was not randomized and the other had a severe local injection site
      abscess on each arm and was hospitalized; causality was assessed as very likely
      and by the end of the study the outcome had resolved. All the patients except 5
      (21%) patients of the placebo group (3 HIV+ and 2 HIV-) reported at least one
      adverse event (AE) during the study. The most frequently occurring AEs among RUTI
      recipients were (% in HIV+/-): injection site reactions [erythema (91/92),
      induration (94/92), local nodules (46/25), local pain (66/75), sterile abscess
      (6/6), swelling (74/83), ulcer (20/11), headache (17/22) and nasopharyngitis
      (20/5)]. These events were mostly mild and well tolerated. Overall, a
      polyantigenic response was observed, which differed by HIV- status. The best
      polyantigenic response was obtained when administrating 25 ug RUTI, especially in
      HIV-positive subjects which was not increased after the second inoculation.
      CONCLUSION: This Phase II clinical trial demonstrates reasonable tolerability of
      RUTI. The immunogenicity profile of RUTI vaccine in LTBI subjects, even being
      variable among groups, allows us considering one single injection of one of the
      highest doses in future trials, preceded by an extended safety clinical phase.
      TRIAL REGISTRATION: ClinicalTrials.gov NCT01136161.

PMID- 24586913
TI  - MAP3K8 (TPL2/COT) affects obesity-induced adipose tissue inflammation without
      systemic effects in humans and in mice.
AB  - Chronic low-grade inflammation in adipose tissue often accompanies obesity,
      leading to insulin resistance and increasing the risk for metabolic diseases.
      MAP3K8 (TPL2/COT) is an important signal transductor and activator of pro
      inflammatory pathways that has been linked to obesity-induced adipose tissue
      inflammation. We used human adipose tissue biopsies to study the relationship of
      MAP3K8 expression with markers of obesity and expression of pro-inflammatory
      cytokines (IL-1beta, IL-6 and IL-8). Moreover, we evaluated obesity-induced
      adipose tissue inflammation and insulin resistance in mice lacking MAP3K8 and WT
      mice on a high-fat diet (HFD) for 16 weeks. Individuals with a BMI >30 displayed
      a higher mRNA expression of MAP3K8 in adipose tissue compared to individuals with
      a normal BMI. Additionally, high mRNA expression levels of IL-1beta, IL-6 and IL
      8, but not TNF -alpha, in human adipose tissue were associated with higher
      expression of MAP3K8. Moreover, high plasma SAA and CRP did not associate with
      increased MAP3K8 expression in adipose tissue. Similarly, no association was
      found for MAP3K8 expression with plasma insulin or glucose levels. Mice lacking
      MAP3K8 had similar bodyweight gain as WT mice, yet displayed lower mRNA
      expression levels of IL-1beta, IL-6 and CXCL1 in adipose tissue in response to
      the HFD as compared to WT animals. However, MAP3K8 deficient mice were not
      protected against HFD-induced adipose tissue macrophage infiltration or the
      development of insulin resistance. Together, the data in both human and mouse
      show that MAP3K8 is involved in local adipose tissue inflammation, specifically
      for IL-1beta and its responsive cytokines IL-6 and IL-8, but does not seem to
      have systemic effects on insulin resistance. 

PMID- 24586914
TI  - Antimicrobial susceptibility of Vibrio vulnificus and Vibrio parahaemolyticus
      recovered from recreational and commercial areas of Chesapeake Bay and Maryland
      Coastal Bays.
AB  - Vibrio vulnificus and V. parahaemolyticus in the estuarine-marine environment are
      of human health significance and may be increasing in pathogenicity and
      abundance. Vibrio illness originating from dermal contact with Vibrio laden
      waters or through ingestion of seafood originating from such waters can cause
      deleterious health effects, particularly if the strains involved are resistant to
      clinically important antibiotics. The purpose of this study was to evaluate
      antimicrobial susceptibility among these pathogens. Surface-water samples were
      collected from three sites of recreational and commercial importance from July to
      September 2009. Samples were plated onto species-specific media and resulting V.
      vulnificus and V. parahaemolyticus strains were confirmed using polymerase chain
      reaction assays and tested for antimicrobial susceptibility using the
      Sensititre(r) microbroth dilution system. Descriptive statistics, Friedman two
      way Analysis of Variance (ANOVA) and Kruskal-Wallis one-way ANOVA were used to
      analyze the data. Vibrio vulnificus (n = 120) and V. parahaemolyticus (n = 77)
      were isolated from all sampling sites. Most isolates were susceptible to
      antibiotics recommended for treating Vibrio infections, although the majority of
      isolates expressed intermediate resistance to chloramphenicol (78% of V.
      vulnificus, 96% of V. parahaemolyticus). Vibrio parahaemolyticus also
      demonstrated resistance to penicillin (68%). Sampling location or month did not
      significantly impact V. parahaemolyticus resistance patterns, but V. vulnificus
      isolates from St. Martin's River had lower overall intermediate resistance than
      that of the other two sampling sites during the month of July (p = 0.0166).
      Antibiotics recommended to treat adult Vibrio infections were effective in
      suppressing bacterial growth, while some antibiotics recommended for pediatric
      treatment were not effective against some of the recovered isolates. To our
      knowledge, these are the first antimicrobial susceptibility data of V. vulnificus
      and V. parahaemolyticus recovered from the Chesapeake Bay. These data can serve
      as a baseline against which future studies can be compared to evaluate whether
      susceptibilities change over time.

PMID- 24586911
TI  - HIV-1 transmission patterns in antiretroviral therapy-naive, HIV-infected North
      Americans based on phylogenetic analysis by population level and ultra-deep DNA
      sequencing.
AB  - Factors that contribute to the transmission of human immunodeficiency virus type
      1 (HIV-1), especially drug-resistant HIV-1 variants remain a significant public
      health concern. In-depth phylogenetic analyses of viral sequences obtained in the
      screening phase from antiretroviral-naive HIV-infected patients seeking
      enrollment in EPZ108859, a large open-label study in the USA, Canada and Puerto
      Rico (ClinicalTrials.gov NCT00440947) were examined for insights into the roles
      of drug resistance and epidemiological factors that could impact disease
      dissemination. Viral transmission clusters (VTCs) were initially predicted from a
      phylogenetic analysis of population level HIV-1 pol sequences obtained from 690
      antiretroviral-naive subjects in 2007. Subsequently, the predicted VTCs were
      tested for robustness by ultra deep sequencing (UDS) using pyrosequencing
      technology and further phylogenetic analyses. The demographic characteristics of
      clustered and non-clustered subjects were then compared. From 690 subjects, 69
      were assigned to 1 of 30 VTCs, each containing 2 to 5 subjects. Race composition
      of VTCs were significantly more likely to be white (72% vs. 60%; p = 0.04). VTCs
      had fewer reverse transcriptase and major PI resistance mutations (9% vs. 24%; p
      = 0.002) than non-clustered sequences. Both men-who-have-sex-with-men (MSM) (68%
      vs. 48%; p = 0.001) and Canadians (29% vs. 14%; p = 0.03) were significantly more
      frequent in VTCs than non-clustered sequences. Of the 515 subjects who initiated
      antiretroviral therapy, 33 experienced confirmed virologic failure through 144
      weeks while only 3/33 were from VTCs. Fewer VTCs subjects (as compared to those
      with non-clustering virus) had HIV-1 with resistance-associated mutations or
      experienced virologic failure during the course of the study. Our analysis shows
      specific geographical and drug resistance trends that correlate well with
      transmission clusters defined by HIV sequences of similarity. Furthermore, our
      study demonstrates the utility of molecular and epidemiological analysis of VTCs
      for identifying population-specific risks associated with HIV-1 transmission and
      developing effective local healthcare strategies. 

PMID- 24586915
TI  - Seasonal carbonate chemistry covariation with temperature, oxygen, and salinity
      in a fjord estuary: implications for the design of ocean acidification
      experiments.
AB  - Carbonate chemistry variability is often poorly characterized in coastal regions
      and patterns of covariation with other biologically important variables such as
      temperature, oxygen concentration, and salinity are rarely evaluated. This
      absence of information hampers the design and interpretation of ocean
      acidification experiments that aim to characterize biological responses to future
      pCO2 levels relative to contemporary conditions. Here, we analyzed a large
      carbonate chemistry data set from Puget Sound, a fjord estuary on the U.S. west
      coast, and included measurements from three seasons (winter, summer, and fall).
      pCO2 exceeded the 2008-2011 mean atmospheric level (392 uatm) at all depths and
      seasons sampled except for the near-surface waters (< 10 m) in the summer.
      Further, undersaturated conditions with respect to the biogenic carbonate mineral
      aragonite were widespread (Omegaar<1). We show that pCO2 values were relatively
      uniform throughout the water column and across regions in winter, enriched in
      subsurface waters in summer, and in the fall some values exceeded 2500 uatm in
      near-surface waters. Carbonate chemistry covaried to differing levels with
      temperature and oxygen depending primarily on season and secondarily on region.
      Salinity, which varied little (27 to 31), was weakly correlated with carbonate
      chemistry. We illustrate potential high-frequency changes in carbonate chemistry,
      temperature, and oxygen conditions experienced simultaneously by organisms in
      Puget Sound that undergo diel vertical migrations under present-day conditions.
      We used simple calculations to estimate future pCO2 and Omegaar values
      experienced by diel vertical migrators based on an increase in atmospheric CO2.
      Given the potential for non-linear interactions between pCO2 and other abiotic
      variables on physiological and ecological processes, our results provide a basis
      for identifying control conditions in ocean acidification experiments for this
      region, but also highlight the wide range of carbonate chemistry conditions
      organisms may currently experience in this and similar coastal ecosystems. 

PMID- 24586916
TI  - The wheat grain contains pectic domains exhibiting specific spatial and
      development-associated distribution.
AB  - Cell walls are complex structures surrounding plant cells with a composition that
      varies among species and even within a species between organs, cell types and
      development stages. For years, cell walls in wheat grains were described as
      simple walls consisting mostly of arabinoxylans and mixed-linked beta glucans.
      Proteomic and transcriptomic studies identified enzyme families involved in the
      synthesis of many more cell wall polysaccharides in the wheat grains. Here we
      describe the discovery of pectic domains in wheat grain using monoclonal
      antibodies and enzymatic treatment to degrade the major cell wall polymers.
      Distinct spatial distributions were observed for rhamnogalacturonan I present in
      the endosperm and mostly in the aleurone layer and homogalacturonan especially
      found in the outer layers, and tight developmental regulations were unveiled. We
      also uncovered a massive deposition of homogalacturonan via large vesicular
      bodies in the seed coat (testa) beneath a thick cuticle during development. Our
      findings raise questions about the function of pectin in wheat grain. 

PMID- 24586917
TI  - The functional influences of common ABCB1 genetic variants on the inhibition of P
      glycoprotein by Antrodia cinnamomea extracts.
AB  - Antrodia cinnamomea is a traditional healthy food that has been demonstrated to
      possess anti-inflammatory, antioxidative, and anticacer effects. The purpose of
      this study was to evaluate whether the ethanolic extract of A. cinnamomea (EEAC)
      can affect the efflux function of P-glycoprotein (P-gp) and the effect of ABCB1
      genetic variants on the interaction between EEAC and P-gp. To investigate the
      mechanism of this interaction, Flp-InTM-293 cells stably transfected with various
      genotypes of human P-gp were established and the expression of P-gp was confirmed
      by Western blot. The results of the rhodamine 123 efflux assay demonstrated that
      EEAC efficiently inhibited wild-type P-gp function at an IC50 concentration of
      1.51 +/- 0.08 ug/mL through non-competitive inhibition. The IC50 concentrations
      for variant-type 1236T-2677T-3435T P-gp and variant-type 1236T-2677A-3435T P-gp
      were 5.56 +/- 0.49 ug/mL and 3.33+/-0.67 ug/mL, respectively. In addition, the
      inhibition kinetics of EEAC also changed to uncompetitive inhibition in variant
      type 1236T-2677A-3435T P-gp. The ATPase assay revealed that EEAC was an ATPase
      stimulator and was capable of reducing verapamil-induced ATPase levels. These
      results indicate that EEAC may be a potent P-gp inhibitor and higher dosages may
      be required in subjects carrying variant-types P-gp. Further studies are required
      to translate this basic knowledge into clinical applications.

PMID- 24586918
TI  - The physiological and biochemical responses of a medicinal plant (Salvia
      miltiorrhiza L.) to stress caused by various concentrations of NaCl.
AB  - Salvia miltiorrhiza, which is commonly known as Danshen, is a traditional Chinese
      herbal medicine. To illustrate its physiological and biochemical responses to
      salt stress and to evaluate the feasibility of cultivating this plant in saline
      coastal soils, a factorial experiment under hydroponic conditions was arranged on
      the basis of a completely randomised design with three replications. Five
      salinity treatments (0, 25, 50, 75 and 100 mM NaCl) were employed in this
      experiment. The results showed that salinity treatments of <100 mM NaCl did not
      affect the growth of Salvia miltiorrhiza in a morphological sense, but
      significantly inhibit the accumulation of dry matter. Salinity treatments
      significantly decreased the Chl-b content but caused a negligible change in the
      Chl-a content, leading to a conspicuous overall decrease in the T-Chl content.
      The Na(+) content significantly increased with increasing hydroponic salinity but
      the K(+) and Ca(2+) contents were reversed, indicating that a high level of
      external Na(+) resulted in a decrease in both K(+) and Ca(2+) concentrations in
      the organs of Salvia miltiorrhiza. Salt stress significantly decreased the
      superoxide dismutase (SOD) activity of Salvia miltiorrhiza leaves in comparison
      with that of the control. On the contrary, the catalase (CAT) activity in the
      leaves markedly increased with the increasing salinity of the hydroponic
      solution. Moreover, the soluble sugar and protein contents in Salvia miltiorrhiza
      leaves dramatically increased with the increasing salinity of the hydroponic
      solution. These results suggested that antioxidant enzymes and osmolytes are
      partially involved in the adaptive response to salt stress in Salvia
      miltiorrhiza, thereby maintaining better plant growth under saline conditions. 

PMID- 24586920
TI  - A force-based, parallel assay for the quantification of protein-DNA interactions.
AB  - Analysis of transcription factor binding to DNA sequences is of utmost importance
      to understand the intricate regulatory mechanisms that underlie gene expression.
      Several techniques exist that quantify DNA-protein affinity, but they are either
      very time-consuming or suffer from possible misinterpretation due to complicated
      algorithms or approximations like many high-throughput techniques. We present a
      more direct method to quantify DNA-protein interaction in a force-based assay. In
      contrast to single-molecule force spectroscopy, our technique, the Molecular
      Force Assay (MFA), parallelizes force measurements so that it can test one or
      multiple proteins against several DNA sequences in a single experiment. The
      interaction strength is quantified by comparison to the well-defined rupture
      stability of different DNA duplexes. As a proof-of-principle, we measured the
      interaction of the zinc finger construct Zif268/NRE against six different DNA
      constructs. We could show the specificity of our approach and quantify the
      strength of the protein-DNA interaction. 

PMID- 24586919
TI  - Modulation by K+ Plus NH4+ of microsomal (Na+, K+)-ATPase activity in selected
      ontogenetic stages of the diadromous river shrimp Macrobrachium amazonicum
      (Decapoda, Palaemonidae).
AB  - We investigate the synergistic stimulation by K(+) plus NH4 (+) of (Na(+), K(+))
      ATPase activity in microsomal preparations of whole zoea I and decapodid III, and
      in juvenile and adult river shrimp gills. Modulation of (Na(+), K(+))-ATPase
      activity is ontogenetic stage-specific, and particularly distinct between
      juveniles and adults. Although both gill enzymes exhibit two different sites for
      K(+) and NH4 (+) binding, in the juvenile enzyme, these two sites are equivalent:
      binding by both ions results in slightly stimulated activity compared to that of
      a single ionic species. In the adult enzyme, the sites are not equivalent: when
      one ion occupies its specific binding site, (Na(+), K(+))-ATPase activity is
      stimulated synergistically by ~ 50% on binding of the complementary ion.
      Immunolocalization reveals the enzyme to be distributed predominantly throughout
      the intralamellar septum in the gill lamellae of juveniles and adults. Western
      blot analyses demonstrate a single immunoreactive band, suggesting a single
      (Na(+), K(+))-ATPase alpha-subunit isoform that is distributed into different
      density membrane fractions, independently of ontogenetic stage. We propose a
      model for the modulation by K(+) and NH4 (+) of gill (Na(+), K(+))-ATPase
      activity. These findings suggest that the gill enzyme may be regulated by NH4 (+)
      during ontogenetic development in M. amazonicum.

PMID- 24586921
TI  - The self-interaction of a nodavirus replicase is enhanced by mitochondrial
      membrane lipids.
AB  - RNA replication of positive-strand (+)RNA viruses requires the protein-protein
      interactions among viral replicases and the association of viral replicases with
      intracellular membranes. Protein A from Wuhan nodavirus (WhNV), which closely
      associate with mitochondrial membranes, is the sole replicase required for viral
      RNA replication. Here, we studied the direct effects of mitochondrial membrane
      lipids (MMLs) on WhNV protein A activity in vitro. Our investigations revealed
      the self-interaction of WhNV protein A is accomplished via two different patterns
      (i.e., homotypic and heterotypic self-interactions via different interfaces).
      MMLs stimulated the protein A self-interaction, and this stimulation exhibited
      selectivity for specific phospholipids. Moreover, we found that specific
      phospholipids differently favor the two self-interaction patterns. Furthermore,
      manipulating specific phospholipid metabolism affected protein A self-interaction
      and the activity of protein A to replicate RNA in cells. Taken together, our
      findings reveal the direct effects of membrane lipids on a nodaviral RNA
      replicase. 

PMID- 24586922
TI  - Mechanical stress triggers cardiomyocyte autophagy through angiotensin II type 1
      receptor-mediated p38MAP kinase independently of angiotensin II.
AB  - Angiotensin II (Ang II) type 1 (AT1) receptor is known to mediate a variety of
      physiological actions of Ang II including autophagy. However, the role of AT1
      receptor in cardiomyocyte autophagy triggered by mechanical stress still remains
      elusive. The aim of this study was therefore to examine whether and how AT1
      receptor participates in cardiomyocyte autophagy induced by mechanical stresses.
      A 48-hour mechanical stretch and a 4-week transverse aorta constriction (TAC)
      were imposed to cultured cardiomyocytes of neonatal rats and adult male C57B/L6
      mice, respectively, to induce cardiomyocyte hypertrophy prior to the assessment
      of cardiomyocyte autophagy using LC3b-II. Losartan, an AT1 receptor blocker, but
      not PD123319, the AT2 inhibitor, was found to significantly reduce mechanical
      stretch-induced LC3b-II upregulation. Moreover, inhibition of p38MAP kinase
      attenuated not only mechanical stretch-induced cardiomyocyte hypertrophy but also
      autophagy. To the contrary, inhibition of ERK and JNK suppressed cardiac
      hypertrophy but not autophagy. Intriguingly, mechanical stretch-induced autophagy
      was significantly inhibited by Losartan in the absence of Ang II. Taken together,
      our results indicate that mechanical stress triggers cardiomyocyte autophagy
      through AT1 receptor-mediated activation of p38MAP kinase independently of Ang
      II. 

PMID- 24586924
TI  - TALEN-mediated modification of the bovine genome for large-scale production of
      human serum albumin.
AB  - As an initial step towards creating genetically modified cattle as a biopharming
      source of recombinant human serum albumin (rHSA), we report modification of the
      bovine albumin (bA) locus by transcription activator-like effector nuclease
      (TALEN)-stimulated homology-directed repair (HDR). Pedigreed bovine fibroblasts
      were co-transfected with TALENs and an 11.5-kb human serum albumin (HSA) minigene
      donor construct, designed to simultaneously disrupt and replace bovine serum
      albumin (BSA) expression with controlled rHSA expression in both the liver and
      the milk. Targeted integration of the HSA minigene was confirmed in transfected
      fibroblasts at a frequency of approximately 11% and transgenic bovine embryos
      were produced from targeted fibroblasts using somatic cell nuclear transfer
      (SCNT). The research delineated here lays the foundation for the future
      generation of transgenic rHSA cattle with the potential to provide a large-scale,
      reliable, and quality-controlled source of rHSA. 

PMID- 24586923
TI  - Aeromonas hydrophila flagella glycosylation: involvement of a lipid carrier.
AB  - Polar flagellin proteins from Aeromonas hydrophila strain AH-3 (serotype O34)
      were found to be O-glycosylated with a heterogeneous glycan. Mutants unable to
      produce WecP or Gne enzymes showed altered motility, and the study of their polar
      flagellin glycosylation showed that the patterns of glycosylation differed from
      that observed with wild type polar flagellin. This suggested the involvement of a
      lipid carrier in glycosylation. A gene coding for an enzyme linking sugar to a
      lipid carrier was identified in strain AH-3 (WecX) and subsequent mutation
      abolished completely motility, flagella production by EM, and flagellin
      glycosylation. This is the first report of a lipid carrier involved in flagella O
      glycosylation. A molecular model has been proposed. The results obtained
      suggested that the N-acetylhexosamines are N-acetylgalactosamines and that the
      heptasaccharide is completely independent of the O34-antigen lipopolysaccharide.
      Furthermore, by comparing the mutants with differing degrees of polar flagellin
      glycosylation, we established their importance in A. hydrophila flagella
      formation and motility. 

PMID- 24586925
TI  - Seasonal variation and impact of waste-water lagoons as larval habitat on the
      population dynamics of Culicoides sonorensis (Diptera:Ceratpogonidae) at two
      dairy farms in northern California.
AB  - The Sacramento (northern Central) Valley of California (CA) has a hot
      Mediterranean climate and a diverse ecological landscape that is impacted
      extensively by human activities, which include the intensive farming of crops and
      livestock. Waste-water ponds, marshes, and irrigated fields associated with these
      agricultural activities provide abundant larval habitats for C. sonorensis
      midges, in addition to those sites that exist in the natural environment. Within
      this region, C. sonorensis is an important vector of bluetongue (BTV) and related
      viruses that adversely affect the international trade and movement of livestock,
      the economics of livestock production, and animal welfare. To characterize the
      seasonal dynamics of immature and adult C. sonorensis populations, abundance was
      monitored intensively on two dairy farms in the Sacramento Valley from August
      2012- to July 2013. Adults were sampled every two weeks for 52 weeks by trapping
      (CDC style traps without light and baited with dry-ice) along N-S and E-W
      transects on each farm. One farm had large operational waste-water lagoons,
      whereas the lagoon on the other farm was drained and remained dry during the
      study. Spring emergence and seasonal abundance of adult C. sonorensis on both
      farms coincided with rising vernal temperature. Paradoxically, the abundance of
      midges on the farm without a functioning waste-water lagoon was increased as
      compared to abundance on the farm with a waste-water lagoon system, indicating
      that this infrastructure may not serve as the sole, or even the primary larval
      habitat. Adult midges disappeared from both farms from late November until May;
      however, low numbers of parous female midges were detected in traps set during
      daylight in the inter-seasonal winter period. This latter finding is especially
      critical as it provides a potential mechanism for the "overwintering" of BTV in
      temperate regions such as northern CA. Precise documentation of temporal changes
      in the annual abundance and dispersal of Culicoides midges is essential for the
      creation of models to predict BTV infection of livestock and to develop sound
      abatement strategies. 

PMID- 24586926
TI  - Diversity of plasmids encoding virulence and resistance functions in Salmonella
      enterica subsp. enterica serovar Typhimurium monophasic variant 4,[5],12:i:-
      strains circulating in Europe.
AB  - Plasmids encoding resistance and virulence properties in multidrug resistant
      (MDR) Salmonella enterica (S.) serovar Typhimurium monophasic variant 4,[5],12:i:
      isolates recovered from pigs and humans (2006-2008) in Europe were
      characterised. The isolates were selected based on the detection by PCR
      amplification of S. Typhimurium virulence plasmid pSLT genes and were analysed by
      multi-locus sequence typing (MLST). The resistance genes present in the isolates
      and the association of these genes with integrons, transposons and insertion
      sequences were characterised by PCR-sequencing, and their plasmid location was
      determined by alkaline lysis and by S1-nuclease pulsed-field gel electrophoresis
      (PFGE) Southern-blot hybridisation. Plasmids were further analysed by replicon
      typing, plasmid MLST and conjugation experiments. The 10 S. 4,[5],12,i:- selected
      isolates belonged to ST19. Each isolate carried a large plasmid in which MDR with
      pSLT-associated virulence genes were located. After analysis, eight different
      plasmids of three incompatibility groups (IncA/C, IncR and IncF) were detected.
      Two IncA/C plasmids represented novel variants within the plasmid family of the
      S. 4,[5],12:i:- Spanish clone, and carried an empty class 1 integron with a
      conventional qacEDelta1-sul1 3' conserved segment or an In-sul3 type III with
      estX-psp-aadA2-cmlA1-aadA1-qacH variable region linked to tnpA440-sul3, part of
      Tn2, Tn21 and Tn1721 transposons, and ISCR2. Four newly described IncR plasmids
      contained the resistance genes within In-sul3 type I (dfrA12-orfF-aadA2-cmlA1
      aadA1-qacH/tnpA440-sul3) and part of Tn10 [tet(B)]. Two pSLT-derivatives with
      FIIs-ST1+FIB-ST17 replicons carried cmlA1-[aadA1-aadA2]-sul3-dfrA12 and blaTEM-1
      genes linked to an In-sul3 type I integron and to Tn2, respectively. In
      conclusion, three emerging European clones of S. 4,[5],12:i:- harboured MDR
      plasmids encoding additional virulence functions that could contribute
      significantly to their evolutionary success.

PMID- 24586927
TI  - Partial methylation at Am100 in 18S rRNA of baker's yeast reveals ribosome
      heterogeneity on the level of eukaryotic rRNA modification.
AB  - Ribosome heterogeneity is of increasing biological significance and several
      examples have been described for multicellular and single cells organisms. In
      here we show for the first time a variation in ribose methylation within the 18S
      rRNA of Saccharomyces cerevisiae. Using RNA-cleaving DNAzymes, we could
      specifically demonstrate that a significant amount of S. cerevisiae ribosomes are
      not methylated at 2'-O-ribose of A100 residue in the 18S rRNA. Furthermore, using
      LC-UV-MS/MS of a respective 18S rRNA fragment, we could not only corroborate the
      partial methylation at A100, but could also quantify the methylated versus non
      methylated A100 residue. Here, we exhibit that only 68% of A100 in the 18S rRNA
      of S.cerevisiae are methylated at 2'-O ribose sugar. Polysomes also contain a
      similar heterogeneity for methylated Am100, which shows that 40S ribosome
      subunits with and without Am100 participate in translation. Introduction of a
      multicopy plasmid containing the corresponding methylation guide snoRNA gene
      SNR51 led to an increased A100 methylation, suggesting the cellular snR51 level
      to limit the extent of this modification. Partial rRNA modification demonstrates
      a new level of ribosome heterogeneity in eukaryotic cells that might have
      substantial impact on regulation and fine-tuning of the translation process. 

PMID- 24586928
TI  - Serotonin receptors expressed in Drosophila mushroom bodies differentially
      modulate larval locomotion.
AB  - Drosophila melanogaster has been successfully used as a simple model to study the
      cellular and molecular mechanisms underlying behaviors, including the generation
      of motor programs. Thus, it has been shown that, as in vertebrates, CNS biogenic
      amines (BA) including serotonin (5HT) participate in motor control in Drosophila.
      Several evidence show that BA systems innervate an important association area in
      the insect brain previously associated to the planning and/or execution of motor
      programs, the Mushroom Bodies (MB). The main objective of this work is to
      evaluate the contribution of 5HT and its receptors expressed in MB to motor
      behavior in fly larva. Locomotion was evaluated using an automated tracking
      system, in Drosophila larvae (3(rd)-instar) exposed to drugs that affect the
      serotonergic neuronal transmission: alpha-methyl-L-dopa, MDMA and fluoxetine. In
      addition, animals expressing mutations in the 5HT biosynthetic enzymes or in any
      of the previously identified receptors for this amine (5HT1AR, 5HT1BR, 5HT2R and
      5HT7R) were evaluated in their locomotion. Finally, RNAi directed to the
      Drosophila 5HT receptor transcripts were expressed in MB and the effect of this
      manipulation on motor behavior was assessed. Data obtained in the mutants and in
      animals exposed to the serotonergic drugs, suggest that 5HT systems are important
      regulators of motor programs in fly larvae. Studies carried out in animals pan
      neuronally expressing the RNAi for each of the serotonergic receptors, support
      this idea and further suggest that CNS 5HT pathways play a role in motor control.
      Moreover, animals expressing an RNAi for 5HT1BR, 5HT2R and 5HT7R in MB show
      increased motor behavior, while no effect is observed when the RNAi for 5HT1AR is
      expressed in this region. Thus, our data suggest that CNS 5HT systems are
      involved in motor control, and that 5HT receptors expressed in MB differentially
      modulate motor programs in fly larvae. 

PMID- 24586929
TI  - The musicality of non-musicians: an index for assessing musical sophistication in
      the general population.
AB  - Musical skills and expertise vary greatly in Western societies. Individuals can
      differ in their repertoire of musical behaviours as well as in the level of skill
      they display for any single musical behaviour. The types of musical behaviours we
      refer to here are broad, ranging from performance on an instrument and listening
      expertise, to the ability to employ music in functional settings or to
      communicate about music. In this paper, we first describe the concept of 'musical
      sophistication' which can be used to describe the multi-faceted nature of musical
      expertise. Next, we develop a novel measurement instrument, the Goldsmiths
      Musical Sophistication Index (Gold-MSI) to assess self-reported musical skills
      and behaviours on multiple dimensions in the general population using a large
      Internet sample (n = 147,636). Thirdly, we report results from several lab
      studies, demonstrating that the Gold-MSI possesses good psychometric properties,
      and that self-reported musical sophistication is associated with performance on
      two listening tasks. Finally, we identify occupation, occupational status, age,
      gender, and wealth as the main socio-demographic factors associated with musical
      sophistication. Results are discussed in terms of theoretical accounts of
      implicit and statistical music learning and with regard to social conditions of
      sophisticated musical engagement. 

PMID- 24586930
TI  - A single-step method for rapid extraction of total lipids from green microalgae.
AB  - Microalgae produce a wide range of lipid compounds of potential commercial
      interest. Total lipid extraction performed by conventional extraction methods,
      relying on the chloroform-methanol solvent system are too laborious and time
      consuming for screening large numbers of samples. In this study, three previous
      extraction methods devised by Folch et al. (1957), Bligh and Dyer (1959) and
      Selstam and Oquist (1985) were compared and a faster single-step procedure was
      developed for extraction of total lipids from green microalgae. In the single
      step procedure, 8 ml of a 2?1 chloroform-methanol (v/v) mixture was added to
      fresh or frozen microalgal paste or pulverized dry algal biomass contained in a
      glass centrifuge tube. The biomass was manually suspended by vigorously shaking
      the tube for a few seconds and 2 ml of a 0.73% NaCl water solution was added.
      Phase separation was facilitated by 2 min of centrifugation at 350 g and the
      lower phase was recovered for analysis. An uncharacterized microalgal polyculture
      and the green microalgae Scenedesmus dimorphus, Selenastrum minutum, and
      Chlorella protothecoides were subjected to the different extraction methods and
      various techniques of biomass homogenization. The less labour intensive single
      step procedure presented here allowed simultaneous recovery of total lipid
      extracts from multiple samples of green microalgae with quantitative yields and
      fatty acid profiles comparable to those of the previous methods. While the single
      step procedure is highly correlated in lipid extractability (r2 = 0.985) to the
      previous method of Folch et al. (1957), it allowed at least five times higher
      sample throughput.

PMID- 24586931
TI  - The culture of cancer cell lines as tumorspheres does not systematically result
      in cancer stem cell enrichment.
AB  - Cancer stem cells (CSC) have raised great excitement during the last decade and
      are promising targets for an efficient treatment of tumors without relapses and
      metastases. Among the various methods that enable to enrich cancer cell lines in
      CSC, tumorspheres culture has been predominantly used. In this report, we
      attempted to generate tumorspheres from several murine and human cancer cell
      lines: B16-F10, HT-29, MCF-7 and MDA-MB-231 cells. Tumorspheres were obtained
      with variable efficiencies from all cell lines except from MDA-MB-231 cells.
      Then, we studied several CSC characteristics in both tumorspheres and adherent
      cultures of the B16-F10, HT-29 and MCF-7 cells. Unexpectedly, tumorspheres
      forming cells were less clonogenic and, in the case of B16-F10, less
      proliferative than attached cells. In addition, we did not observe any enrichment
      in the population expressing CSC surface markers in tumorspheres from B16-F10
      (CD133, CD44 and CD24 markers) or MCF-7 (CD44 and CD24 markers) cells. On the
      contrary, tumorspheres culture of HT-29 cells appeared to enrich in cells
      expressing colon CSC markers, i.e. CD133 and CD44 proteins. For the B16-F10 cell
      line, when 1 000 cells were injected in syngenic C57BL/6 mice, tumorspheres
      forming cells displayed a significantly lower tumorigenic potential than adherent
      cells. Finally, tumorspheres culture of B16-F10 cells induced a down-regulation
      of vimentin which could explain, at least partially, the lower tumorigenicity of
      tumorspheres-forming cells. All these results, along with the literature,
      indicate that tumorspheres culture of cancer cell lines can induce an enrichment
      in CSC but in a cell line-dependent manner. In conclusion, extensive
      characterization of CSC properties in tumorspheres derived from any cancer cell
      line or cancer tissue must be performed in order to ensure that the generated
      tumorspheres are actually enriched in CSC. 

PMID- 24586932
TI  - QTL analysis of Kernel-related traits in maize using an immortalized F2
      population.
AB  - Kernel size and weight are important determinants of grain yield in maize. In
      this study, multivariate conditional and unconditional quantitative trait loci
      (QTL), and digenic epistatic analyses were utilized in order to elucidate the
      genetic basis for these kernel-related traits. Five kernel-related traits,
      including kernel weight (KW), volume (KV), length (KL), thickness (KT), and width
      (KWI), were collected from an immortalized F2 (IF2) maize population comprising
      of 243 crosses performed at two separate locations over a span of two years. A
      total of 54 unconditional main QTL for these five kernel-related traits were
      identified, many of which were clustered in chromosomal bins 6.04-6.06, 7.02
      7.03, and 10.06-10.07. In addition, qKL3, qKWI6, qKV10a, qKV10b, qKW10a, and
      qKW7a were detected across multiple environments. Sixteen main QTL were
      identified for KW conditioned on the other four kernel traits (KL, KWI, KT, and
      KV). Thirteen main QTL were identified for KV conditioned on three kernel-shape
      traits. Conditional mapping analysis revealed that KWI and KV had the strongest
      influence on KW at the individual QTL level, followed by KT, and then KL; KV was
      mostly strongly influenced by KT, followed by KWI, and was least impacted by KL.
      Digenic epistatic analysis identified 18 digenic interactions involving 34 loci
      over the entire genome. However, only a small proportion of them were identical
      to the main QTL we detected. Additionally, conditional digenic epistatic analysis
      revealed that the digenic epistasis for KW and KV were entirely determined by
      their constituent traits. The main QTL identified in this study for determining
      kernel-related traits with high broad-sense heritability may play important roles
      during kernel development. Furthermore, digenic interactions were shown to exert
      relatively large effects on KL (the highest AA and DD effects were 4.6% and 6.7%,
      respectively) and KT (the highest AA effects were 4.3%). 

PMID- 24586933
TI  - Role of the ERK pathway for oxidant-induced parthanatos in human lymphocytes.
AB  - Reactive oxygen species (ROS) are formed by myeloid cells as a defense strategy
      against microorganisms. ROS however also trigger poly(ADP-ribose) polymerase 1-
      (PARP-1) dependent cell death (parthanatos) in adjacent lymphocytes, which has
      been forwarded as a mechanism of immune escape in several forms of cancer. The
      present study assessed the role of mitogen-activated protein kinases (MAPKs), in
      particular the extracellular signal-regulated kinase (ERK), in ROS-induced signal
      transduction leading to lymphocyte parthanatos. We report that inhibitors of
      ERK1/2 phosphorylation upheld natural killer (NK) cell-mediated cytotoxicity
      under conditions of oxidative stress and rescued NK cells and CD8(+) T
      lymphocytes from cell death induced by ROS-producing monocytes. ERK1/2
      phosphorylation inhibition also protected lymphocytes from cell death induced by
      exogenous hydrogen peroxide (H2O2) and from ROS generated by xanthine oxidase or
      glucose oxidase. Phosphorylation of ERK1/2 was observed in lymphocytes shortly
      after exposure to ROS. ROS-generating myeloid cells and exogenous H2O2 triggered
      PARP 1-dependent accumulation of poly ADP-ribose (PAR), which was prevented by
      ERK pathway inhibitors. ERK1/2 phosphorylation was induced by ROS independently
      of PARP-1. Our findings are suggestive of a role for ERK1/2 in ROS-induced
      lymphocyte parthanatos, and that the ERK axis may provide a therapeutic target
      for the protection of lymphocytes against oxidative stress. 

PMID- 24586934
TI  - Therapeutic administration of the chemokine CXCL1/KC abrogates autoimmune
      inflammatory heart disease.
AB  - Myocarditis, often due to an aberrant immune response to infection, is a major
      cause of dilated cardiomyopathy. Microbial pattern recognition receptors, such as
      TLRs, orchestrate the cytokine and chemokine responses that augment or limit the
      severity of myocarditis. Using the mouse model of experimental autoimmune
      myocarditis (EAM), in which disease is induced by immunization with a heart
      specific self peptide and the agonist to multiple TLRs, complete Freund's
      adjuvant, we found that increased serum concentrations of the chemokine CXCL1/KC
      correlated directly with decreased severity of myocarditis. To directly test
      whether CXCL1/KC caused the amelioration of myocarditis, we treated mice, after
      challenge with heart-specific self peptide, with exogenous recombinant CXCL1/KC.
      We found that the administration of recombinant mouse CXCL1/KC completely
      abrogated heart inflammatory infiltration and cardiomyocyte damage. Moreover, we
      show that TLR4 signaling is required to increase serum protein concentrations of
      CXCL1/KC in EAM, and we demonstrate that the administration of the TLR4 agonist
      LPS significantly decreased severity and prevalence of EAM and reduced the number
      of heart-specific self peptide reactive effector T cells. These findings reveal a
      novel function of CXCL1/KC in the context of organ-specific autoimmune disease
      that may prove useful for the treatment of inflammatory conditions that underlie
      human heart disease. 

PMID- 24586935
TI  - Ectopic TLX1 expression accelerates malignancies in mice deficient in DNA-PK.
AB  - The noncluster homeobox gene HOX11/TLX1 (TLX1) is detected at the breakpoint of
      the t(10;14)(q24;q11) chromosome translocation in patients with T cell acute
      lymphoblastic leukemia (T-ALL). This translocation results in the inappropriate
      expression of TLX1 in T cells. The oncogenic potential of TLX1 was demonstrated
      in IgHMU-TLX1(Tg) mice which develop mature B cell lymphoma after a long latency
      period, suggesting the requirement of additional mutations to initiate
      malignancy. To determine whether dysregulation of genes involved in the DNA
      damage response contributed to tumor progression, we crossed IgHMU-TLX1(Tg) mice
      with mice deficient in the DNA repair enzyme DNA-PK (Prkdc(Scid/Scid) mice). IgHu
      TLX1(Tg)Prkdc(Scid/Scid) mice developed T-ALL and acute myeloid leukemia (AML)
      with reduced latency relative to control Prkdc(Scid/Scid) mice. Further analysis
      of thymi from premalignant mice revealed greater thymic cellularity concomitant
      with increased thymocyte proliferation and decreased apoptotic index. Moreover,
      premalignant and malignant thymocytes exhibited impaired spindle checkpoint
      function, in association with aneuploid karyotypes. Gene expression profiling of
      premalignant IgHu-TLX1(Tg)Prkdc(Scid/Scid) thymocytes revealed dysregulated
      expression of cell cycle, apoptotic and mitotic spindle checkpoint genes in
      double negative 2 (DN2) and DN3 stage thymocytes. Collectively, these findings
      reveal a novel synergy between TLX1 and impaired DNA repair pathway in
      leukemogenesis. 

PMID- 24586937
TI  - Antiviral strategies for emerging influenza viruses in remote communities.
AB  - BACKGROUND: Due to the lack of timely access to resources for critical care,
      strategic use of antiviral drugs is crucial for mitigating the impact of novel
      influenza viruses with pandemic potential in remote and isolated communities. We
      sought to evaluate the effect of antiviral treatment and prophylaxis of close
      contacts in a Canadian remote northern community. METHODS: We used an agent
      based, discrete-time simulation model for disease spread in a remote community,
      which was developed as an in-silico population using population census data.
      Relative and cumulative age-specific attack rates, and the total number of
      infections in simulated model scenarios were obtained. RESULTS: We found that
      early initiation of antiviral treatment is more critical for lowering attack
      rates in a remote setting with a low population-average age compared to an urban
      population. Our results show that a significant reduction in the relative, age
      specific attack rates due to increasing treatment coverage does not necessarily
      translate to a significant reduction in the overall arrack rate. When treatment
      coverage varies from low to moderate, targeted prophylaxis has a very limited
      impact in reducing attack rates and should be offered at a low level (below 10%)
      to avoid excessive waste of drugs. CONCLUSIONS: In contrast to previous work, for
      conservative treatment coverages, our results do not provide any convincing
      evidence for the implementation of targeted prophylaxis. The findings suggest
      that public health strategies in remote communities should focus on the wider
      availability (higher coverage) and timely distribution of antiviral drugs for
      treatment of clinically ill individuals.

PMID- 24586936
TI  - Adverse lifestyle leads to an annual excess of 2 million deaths in China.
AB  - BACKGROUND: Adverse lifestyle factors have been associated with increased
      mortality, but data are lacking on their combined effect in developing
      populations, which we address in the present study. METHODS: In a death registry
      based, case-control study among Hong Kong Chinese aged 30+y, proxy-reported
      lifestyle factors 10 y ago were collected for 21,363 cases (81% of all deaths)
      and 12,048 living controls. Risks associated with poor diet, inactivity, heavy
      alcohol intake, and smoking for all-cause and cause-specific mortality, adjusting
      for potential confounders, were determined, and excess deaths for the Chinese
      population were calculated. RESULTS: Adjusted odds ratios for all-cause mortality
      were 1.15 (95% CI 1.09, 1.23), 1.34 (1.27, 1.43), 1.36 (1.21, 1.52), and 1.58
      (1.46, 1.70) for poor diet, inactivity, heavy alcohol intake and smoking,
      respectively. Increasing numbers of adverse lifestyle factors were associated
      with a dose-dependent increase in adjusted odds ratios of 1.30 (1.20, 1.40), 1.67
      (1.54, 1.81), 2.32 (2.08, 2.60), and 3.85 (3.12, 4.75) for 1, 2, 3, and 4 risk
      factors relative to those with none. The population attributable fraction for all
      cause, all-CVD and all-cancer mortality were 26.6%, 15.0%, and 32.1%, resulting
      in an excess of 2,017,541; 489,884; and 607,517 deaths annually, respectively.
      Although smoking was associated with the greatest excess loss of life (867,530),
      heavy drinking (680,466), and physical inactivity (678,317) were similarly
      important. CONCLUSION: Adverse lifestyle factors contribute to one quarter of all
      deaths in China. Improving lifestyle practices, particularly focussing on
      moderating alcohol intake and increasing activity, and smoking cessation are
      critical to reducing the lifestyle-associated health burden.

PMID- 24586938
TI  - Multiple renal cyst development but not situs abnormalities in transgenic RNAi
      mice against Inv::GFP rescue gene.
AB  - In this study we generated RNA interference (RNAi)-mediated gene knockdown
      transgenic mice (transgenic RNAi mice) against the functional Inv gene. Inv
      mutant mice show consistently reversed internal organs (situs inversus), multiple
      renal cysts and neonatal lethality. The Inv::GFP-rescue mice, which introduced
      the Inv::GFP fusion gene, can rescue inv mutant mice phenotypes. This indicates
      that the Inv::GFP gene is functional in vivo. To analyze the physiological
      functions of the Inv gene, and to demonstrate the availability of transgenic RNAi
      mice, we introduced a short hairpin RNA expression vector against GFP mRNA into
      Inv::GFP-rescue mice and analyzed the gene silencing effects and Inv functions by
      examining phenotypes. Transgenic RNAi mice with the Inv::GFP-rescue gene (Inv-KD
      mice) down-regulated Inv::GFP fusion protein and showed hypomorphic phenotypes of
      inv mutant mice, such as renal cyst development, but not situs abnormalities or
      postnatal lethality. This indicates that shRNAi-mediated gene silencing systems
      that target the tag sequence of the fusion gene work properly in vivo, and
      suggests that a relatively high level of Inv protein is required for kidney
      development in contrast to left/right axis determination. Inv::GFP protein was
      significantly down-regulated in the germ cells of Inv-KD mice testis compared
      with somatic cells, suggesting the existence of a testicular germ cell-specific
      enhanced RNAi system that regulates germ cell development. The Inv-KD mouse is
      useful for studying Inv gene functions in adult tissue that are unable to be
      analyzed in inv mutant mice showing postnatal lethality. In addition, the shRNA
      based gene silencing system against the tag sequence of the fusion gene can be
      utilized as a new technique to regulate gene expression in either in vitro or in
      vivo experiments. 

PMID- 24586939
TI  - The phzA2-G2 transcript exhibits direct RsmA-mediated activation in Pseudomonas
      aeruginosa M18.
AB  - In bacteria, RNA-binding proteins of the RsmA/CsrA family act as post
      transcriptional regulators that modulate translation initiation at target
      transcripts. The Pseudomonas aeruginosa genome contains two phenazine
      biosynthetic (phz) gene clusters, phzA1-G1 (phz1) and phzA2-G2 (phz2), each of
      which is responsible for phenazine-1-carboxylic acid (PCA) biosynthesis. In the
      present study, we show that RsmA exhibits differential gene regulation on two phz
      clusters in P. aeruginosa M18 at the post-transcriptional level. Based on the
      sequence analysis, four GGA motifs, the potential RsmA binding sites, are found
      on the 5'-untranslated region (UTR) of the phz2 transcript. Studies with a series
      of lacZ reporter fusions, and gel mobility shift assays suggest that the third
      GGA motif (S3), located 21 nucleotides upstream of the Shine-Dalgarno (SD)
      sequence, is involved in direct RsmA-mediated activation of phz2 expression. We
      therefore propose a novel model in which the binding of RsmA to the target S3
      results in the destabilization of the stem-loop structure and the enhancement of
      ribosome access. This model could be fully supported by RNA structure prediction,
      free energy calculations, and nucleotide replacement studies. In contrast,
      various RsmA-mediated translation repression mechanisms have been identified in
      which RsmA binds near the SD sequence of target transcripts, thereby blocking
      ribosome access. Similarly, RsmA is shown to negatively regulate phz1 expression.
      Our new findings suggest that the differential regulation exerted by RsmA on the
      two phz clusters may confer an advantage to P. aeruginosa over other pseudomonads
      containing only a single phz cluster in their genomes. 

PMID- 24586940
TI  - PPARgamma ligands decrease hydrostatic pressure-induced platelet aggregation and
      proinflammatory activity.
AB  - Hypertension is known to be associated with platelet overactivity, but the direct
      effects of hydrostatic pressure on platelet function remain unclear. The present
      study sought to investigate whether elevated hydrostatic pressure is responsible
      for platelet activation and to address the potential role of peroxisome
      proliferator-activated receptor-gamma (PPARgamma). We observed that hypertensive
      patients had significantly higher platelet volume and rate of ADP-induced
      platelets aggregation compared to the controls. In vitro, Primary human platelets
      were cultured under standard (0 mmHg) or increased (120, 180, 240 mmHg)
      hydrostatic pressure for 18 h. Exposure to elevated pressure was associated with
      morphological changes in platelets. Platelet aggregation and PAC-1 (the active
      confirmation of GPIIb/IIIa) binding were increased, CD40L was translocated from
      cytoplasm to the surface of platelet and soluble CD40L (sCD40L) was released into
      the medium in response to elevated hydrostatic pressure (180 and 240 mmHg). The
      PPARgamma activity was up-regulated as the pressure was increased from 120 mmHg
      to 180 mmHg. Pressure-induced platelet aggregation, PAC-1 binding, and
      translocation and release of CD40L were all attenuated by the PPARgamma agonist
      Thiazolidinediones (TZDs). These results demonstrate that platelet activation and
      aggregation are increased by exposure to elevated pressure and that PPARgamma may
      modulate platelet activation induced by high hydrostatic pressure. 

PMID- 24586941
TI  - The effect of individual and neighborhood socioeconomic status on gastric cancer
      survival.
AB  - PURPOSE: Gastric cancer is a leading cause of death, particularly in the
      developing world. The literature reports individual socioeconomic status (SES) or
      neighborhood SES as related to survival, but the effect of both has not been
      studied. This study investigated the effect of individual and neighborhood SES
      simultaneously on mortality in gastric cancer patients in Taiwan. MATERIALS AND
      METHODS: A study was conducted of 3,396 patients diagnosed with gastric cancer
      between 2002 and 2006. Each patient was followed for five years or until death.
      Individual SES was defined by income-related insurance premium (low, moderate,
      and high). Neighborhood SES was based on household income dichotomized into
      advantaged and disadvantaged areas. Multilevel logistic regression model was used
      to compare survival rates by SES group after adjusting for possible confounding
      factors. RESULTS: In patients younger than 65 years, 5-year overall survival
      rates were lowest for those with low individual SES. After adjusting for patient
      characteristics (age, gender, Charlson Comorbidity Index Score), gastric cancer
      patients with high individual SES had 68% risk reduction of mortality (adjusted
      odds ratio [OR] of mortality, 0.32; 95% confidence interval [CI], 0.17-0.61).
      Patients aged 65 and above had no statistically significant difference in
      mortality rates by individual SES group. Different neighborhood SES did not
      statistically differ in the survival rates. CONCLUSION: Gastric cancer patients
      aged less than 65 years old with low individual SES have higher risk of
      mortality, even under an universal healthcare system. Public health strategies,
      education and welfare policies should seek to correct the inequality in gastric
      cancer survival, especially in those with lower individual SES.

PMID- 24586942
TI  - Obstructive sleep apnea and the risk of atopic dermatitis: a population-based
      case control study.
AB  - BACKGROUND: Obstructive sleep apnea (OSA) is associated with systemic
      inflammation and induces various comorbid medical diseases. To date, no study has
      explored the relationship between OSA and atopic dermatitis (AD), an inflammatory
      and autoimmune skin disorder. This study investigated the longitudinal risk for
      AD in patients with OSA. METHODS: A random sample of 1,000,000 individuals from
      Taiwan's National Health Insurance database was collected. From this sample, 1222
      patients with newly-diagnosed OSA between 2000 and 2005 were identified and
      compared with a matched cohort of 18330 patients without OSA. All patients were
      tracked for 5.5 years from the index date in order to identify which patients
      subsequently developed AD. RESULTS: During the 5.5-year follow-up period, the
      incidence rates of AD in the OSA cohort and comparison groups were 9.81 and 6.21
      per 1000 person-years, respectively. After adjustment for age, gender, diabetes,
      hypertension, coronary heart disease, obesity, allergy, allergic rhinitis,
      asthma, monthly income, and geographic location, patients with OSA were 1.5-times
      more likely to develop AD than patients without OSA (95% CI = 1.15-1.95, p =
      0.0025). The hazard risk for AD was greater in male OSA patients and young OSA
      patients (0-18 and 19-34 years), adjusted HRs being 1.53 (95% CI = 1.14-2.06, p =
      0.005), 4.01(95% CI = 1.57-10.26, p = 0.0038) and 1.75(95% CI = 1.00-3.04, p =
      0.0483), respectively. The log-rank test indicated that OSA patients <35-years
      old had significantly higher cumulative incidence rates of AD than those patient
      of the same age in the comparison group (p = 0.0001). CONCLUSION: Patients with
      OSA, especially male patients and younger patients, are at an increased risk for
      AD later in life.

PMID- 24586943
TI  - Two polymorphisms facilitate differences in plasticity between two chicken major
      histocompatibility complex class I proteins.
AB  - Major histocompatibility complex class I molecules (MHC I) present peptides to
      cytotoxic T-cells at the surface of almost all nucleated cells. The function of
      MHC I molecules is to select high affinity peptides from a large intracellular
      pool and they are assisted in this process by co-factor molecules, notably
      tapasin. In contrast to mammals, MHC homozygous chickens express a single MHC I
      gene locus, termed BF2, which is hypothesised to have co-evolved with the highly
      polymorphic tapasin within stable haplotypes. The BF2 molecules of the B15 and
      B19 haplotypes have recently been shown to differ in their interactions with
      tapasin and in their peptide selection properties. This study investigated
      whether these observations might be explained by differences in the protein
      plasticity that is encoded into the MHC I structure by primary sequence
      polymorphisms. Furthermore, we aimed to demonstrate the utility of a
      complimentary modelling approach to the understanding of complex experimental
      data. Combining mechanistic molecular dynamics simulations and the primary
      sequence based technique of statistical coupling analysis, we show how two of the
      eight polymorphisms between BF2*15?01 and BF2*19?01 facilitate differences in
      plasticity. We show that BF2*15?01 is intrinsically more plastic than BF2*19?01,
      exploring more conformations in the absence of peptide. We identify a protein
      sector of contiguous residues connecting the membrane bound alpha3 domain and the
      heavy chain peptide binding site. This sector contains two of the eight
      polymorphic residues. One is residue 22 in the peptide binding domain and the
      other 220 is in the alpha3 domain, a putative tapasin binding site. These
      observations are in correspondence with the experimentally observed functional
      differences of these molecules and suggest a mechanism for how modulation of MHC
      I plasticity by tapasin catalyses peptide selection allosterically. 

PMID- 24586944
TI  - In vitro and in vivo activity of a novel locked nucleic acid (LNA)-inhibitor-miR
      221 against multiple myeloma cells.
AB  - BACKGROUND & AIM: The miR-221/222 cluster is upregulated in malignant plasma
      cells from multiple myeloma (MM) patients harboring the t(4;14) translocation. We
      previously reported that silencing of miR-221/222 by an antisense oligonucleotide
      induces anti-MM activity and upregulates canonical miR-221/222 targets. The in
      vivo anti-tumor activity occurred when miR-221/222 inhibitors were delivered
      directly into MM xenografts. The aim of the present study was to evaluate the
      anti-MM activity of a novel phosphorothioate modified backbone 13-mer locked
      nucleic acid (LNA)-Inhibitor-miR-221 (LNA-i-miR-221) specifically designed for
      systemic delivery. METHODS: In vitro anti-MM activity of LNA-i-miR-221 was
      evaluated by cell proliferation and BrdU uptake assays. In vivo studies were
      performed with non-obese diabetic/severe combined immunodeficient (NOD.SCID) mice
      bearing t(4;14) MM xenografts, which were intraperitoneally or intravenously
      treated with naked LNA-i-miR-221. RNA extracts from retrieved tumors were
      analyzed for miR-221 levels and modulation of canonical targets expression. H&E
      staining and immunohistochemistry were performed on retrieved tumors and mouse
      vital organs. RESULTS: In vitro, LNA-i-miR-221 exerted strong antagonistic
      activity against miR-221 and induced upregulation of the endogenous target
      p27Kip1. It had a marked anti-proliferative effect on t(4;14)-translocated MM
      cells but not on MM cells not carrying the translocation and not overexpressing
      miR-221. In vivo, systemic treatment with LNA-i-miR-221 triggered significant
      anti-tumor activity against t(4;14) MM xenografts; it also induced miR-221
      downregulation, upregulated p27Kip1 and reduced Ki-67. No behavioral changes or
      organ-related toxicity were observed in mice as a consequence of treatments.
      CONCLUSIONS: LNA-i-miR-221 is a highly stable, effective agent against t(4;14) MM
      cells, and is suitable for systemic use. These data provide the rationale for the
      clinical development of LNA-i-miR-221 for the treatment of MM.

PMID- 24586945
TI  - Area level deprivation is an independent determinant of prevalent type 2 diabetes
      and obesity at the national level in Germany. Results from the National Telephone
      Health Interview Surveys 'German Health Update' GEDA 2009 and 2010.
AB  - OBJECTIVE: There is increasing evidence that prevention programmes for type 2
      diabetes mellitus (T2DM) and obesity need to consider individual and regional
      risk factors. Our objective is to assess the independent association of area
      level deprivation with T2DM and obesity controlling for individual risk factors
      in a large study covering the whole of Germany. METHODS: We combined data from
      two consecutive waves of the national health interview survey 'GEDA' conducted by
      the Robert Koch Institute in 2009 and 2010. Data collection was based on computer
      assisted telephone interviews. After exclusion of participants <30 years of age
      and those with missing responses, we included n=33,690 participants in our
      analyses. The outcome variables were the 12-month prevalence of known T2DM and
      the prevalence of obesity (BMI >= 30 kg/m(2)). We also controlled for age, sex,
      BMI, smoking, sport, living with a partner and education. Area level deprivation
      of the districts was defined by the German Index of Multiple Deprivation.
      Logistic multilevel regression models were performed using the software SAS 9.2.
      RESULTS: Of all men and women living in the most deprived areas, 8.6% had T2DM
      and 16.9% were obese (least deprived areas: 5.8% for T2DM and 13.7% for obesity).
      For women, higher area level deprivation and lower educational level were both
      independently associated with higher T2DM and obesity prevalence [highest area
      level deprivation: OR 1.28 (95% CI: 1.05-1.55) for T2DM and OR 1.28 (95% CI: 1.10
      1.49) for obesity]. For men, a similar association was only found for obesity [OR
      1.20 (95% CI: 1.02-1.41)], but not for T2DM. CONCLUSION: Area level deprivation
      is an independent, important determinant of T2DM and obesity prevalence in
      Germany. Identifying and targeting specific area-based risk factors should be
      considered an essential public health issue relevant to increasing the
      effectiveness of diabetes and obesity prevention.

PMID- 24586947
TI  - Alien roadside species more easily invade alpine than lowland plant communities
      in a subarctic mountain ecosystem.
AB  - Effects of roads on plant communities are not well known in cold-climate mountain
      ecosystems, where road building and development are expected to increase in
      future decades. Knowledge of the sensitivity of mountain plant communities to
      disturbance by roads is however important for future conservation purposes. We
      investigate the effects of roads on species richness and composition, including
      the plant strategies that are most affected, along three elevational gradients in
      a subarctic mountain ecosystem. We also examine whether mountain roads promote
      the introduction and invasion of alien plant species from the lowlands to the
      alpine zone. Observations of plant community composition were made together with
      abiotic, biotic and anthropogenic factors in 60 T-shaped transects. Alpine plant
      communities reacted differently to road disturbances than their lowland
      counterparts. On high elevations, the roadside species composition was more
      similar to that of the local natural communities. Less competitive and ruderal
      species were present at high compared with lower elevation roadsides. While the
      effects of roads thus seem to be mitigated in the alpine environment for plant
      species in general, mountain plant communities are more invasible than lowland
      communities. More precisely, relatively more alien species present in the
      roadside were found to invade into the surrounding natural community at high
      compared to low elevations. We conclude that effects of roads and introduction of
      alien species in lowlands cannot simply be extrapolated to the alpine and
      subarctic environment. 

PMID- 24586946
TI  - 5-HT1A/1B receptors as targets for optimizing pigmentary responses in C57BL/6
      mouse skin to stress.
AB  - Stress has been reported to induce alterations of skin pigmentary response. Acute
      stress is associated with increased turnover of serotonin (5-hydroxytryptamine; 5
      HT) whereas chronic stress causes a decrease. 5-HT receptors have been detected
      in pigment cells, indicating their role in skin pigmentation. To ascertain the
      precise role of 5-HT in stress-induced pigmentary responses, C57BL/6 mice were
      subjected to chronic restraint stress and chronic unpredictable mild stress (CRS
      and CUMS, two models of chronic stress) for 21 days, finally resulting in
      abnormal pigmentary responses. Subsequently, stressed mice were characterized by
      the absence of a black pigment in dorsal coat. The down-regulation of tyrosinase
      (TYR) and tyrosinase-related proteins (TRP1 and TRP2) expression in stressed skin
      was accompanied by reduced levels of 5-HT and decreased expression of 5-HT
      receptor (5-HTR) system. In both murine B16F10 melanoma cells and normal human
      melanocytes (NHMCs), 5-HT had a stimulatory effect on melanin production,
      dendricity and migration. When treated with 5-HT in cultured hair follicles
      (HFs), the increased expression of melanogenesis-related genes and the activation
      of 5-HT1A, 1B and 7 receptors also occurred. The serum obtained from stressed
      mice showed significantly decreased tyrosinase activity in NHMCs compared to that
      from nonstressed mice. The decrease in tyrosinase activity was further augmented
      in the presence of 5-HTR1A, 1B and 7 antagonists, WAY100635, SB216641 and
      SB269970. In vivo, stressed mice received 5-HT precursor 5-hydroxy-l-tryptophan
      (5-HTP), a member of the class of selective serotonin reuptake inhibitors
      (fluoxetine; FX) and 5-HTR1A/1B agonists (8-OH-DPAT/CP94253), finally
      contributing to the normalization of pigmentary responses. Taken together, these
      data strongly suggest that the serotoninergic system plays an important role in
      the regulation of stress-induced depigmentation, which can be mediated by 5
      HT1A/1B receptors. 5-HT and 5-HTR1A/1B may constitute novel targets for therapy
      of skin hypopigmentation disorders, especially those worsened with stress. 

PMID- 24586948
TI  - Altered cortical swallowing processing in patients with functional dysphagia: a
      preliminary study.
AB  - OBJECTIVE: Current neuroimaging research on functional disturbances provides
      growing evidence for objective neuronal correlates of allegedly psychogenic
      symptoms, thereby shifting the disease concept from a psychological towards a
      neurobiological model. Functional dysphagia is such a rare condition, whose
      pathogenetic mechanism is largely unknown. In the absence of any organic reason
      for a patient's persistent swallowing complaints, sensorimotor processing
      abnormalities involving central neural pathways constitute a potential etiology.
      METHODS: In this pilot study we measured cortical swallow-related activation in 5
      patients diagnosed with functional dysphagia and a matched group of healthy
      subjects applying magnetoencephalography. Source localization of cortical
      activation was done with synthetic aperture magnetometry. To test for significant
      differences in cortical swallowing processing between groups, a non-parametric
      permutation test was afterwards performed on individual source localization maps.
      RESULTS: Swallowing task performance was comparable between groups. In relation
      to control subjects, in whom activation was symmetrically distributed in rostro
      medial parts of the sensorimotor cortices of both hemispheres, patients showed
      prominent activation of the right insula, dorsolateral prefrontal cortex and
      lateral premotor, motor as well as inferolateral parietal cortex. Furthermore,
      activation was markedly reduced in the left medial primary sensory cortex as well
      as right medial sensorimotor cortex and adjacent supplementary motor area
      (p<0.01). CONCLUSIONS: Functional dysphagia--a condition with assumed normal
      brain function--seems to be associated with distinctive changes of the swallow
      related cortical activation pattern. Alterations may reflect exaggerated
      activation of a widely distributed vigilance, self-monitoring and salience rating
      network that interferes with down-stream deglutition sensorimotor control.

PMID- 24586949
TI  - Nasal screening for Staphylococcus aureus--daily routine with improvement
      potentials.
AB  - OBJECTIVES: Staphylococcus aureus causes purulent bacterial infections with a
      considerable number of life-threatening complications and thus, is a serious cost
      factor in public health. Up to 50% of a given population could asymptomatically
      carry Staphylococcus aureus in their nares, thereby serving as a source for
      contact transmissions and endogenous infections. Nasal swab-based screening
      techniques are widely used to identify suchcarriers. This study investigated the
      skill of medical professionals in taking nasal swabs and the effect of teaching
      on improving bacterial recovery rates. METHODS: 364 persons with different
      medical educational background participated in this study. A novel anatomically
      correct artificial nose model was implemented and inoculated with a numerically
      defined mixture of Staphylococcus aureus and Staphylococcus epidermidis bacteria.
      Utilizing regular clinical swabs, participants performed screening of the
      inoculated nose models before and after standardized theoretical, visual, and
      practical teaching. Recovery of bacteria was measured by standard viable count
      techniques. Data were analyzed statistically by nonparametric tests. RESULTS: It
      could be demonstrated that combined theoretical and practical teaching improved
      bacterial recovery rates. Even experienced medical professionals increased their
      detection levels after training. Recovery rates of bacteria varied significantly
      between trained (158.1 CFU) and untrained (47.5 CFU) participants (Wilcoxon test,
      p<0.001; Kolmogorov-Smirnov test, p<0.001). CONCLUSIONS: Swabs are commonly used
      to detect nasal carriage of Staphylococcus aureus in patients. The present
      teaching algorithm combined with the novel nose model offers an excellent
      precondition to improve knowledge and performance of this technique. Increased
      detection rates may prevent from contact transmission due to suboptimum hygienic
      patient handling. Consecutively, this effect could reduce costs for patient care.
      This study highlights the tremendous potential of combined theoretical, visual,
      and practical teaching methods in this field--and uncovers its actual necessity.
      Therefore, this training method can be recommended for all medical institutions.

PMID- 24586950
TI  - Biosensor-based approach identifies four distinct calmodulin-binding domains in
      the G protein-coupled estrogen receptor 1.
AB  - The G protein-coupled estrogen receptor 1 (GPER) has been demonstrated to
      participate in many cellular functions, but its regulatory inputs are not clearly
      understood. Here we describe a new approach that identifies GPER as a calmodulin
      binding protein, locates interaction sites, and characterizes their binding
      properties. GPER coimmunoprecipitates with calmodulin in primary vascular smooth
      muscle cells under resting conditions, which is enhanced upon acute treatment
      with either specific ligands or a Ca(2+)-elevating agent. To confirm direct
      interaction and locate the calmodulin-binding domain(s), we designed a series of
      FRET biosensors that consist of enhanced cyan and yellow fluorescent proteins
      flanking each of GPER's submembrane domains (SMDs). Responses of these biosensors
      showed that all four submembrane domains directly bind calmodulin. Modifications
      of biosensor linker identified domains that display the strongest calmodulin
      binding affinities and largest biosensor dynamics, including a.a. 83-93, 150-175,
      242-259, 330-351, corresponding respectively to SMDs 1, 2, 3, and the juxta
      membranous section of SMD4. These biosensors bind calmodulin in a strictly Ca(2+)
      dependent fashion and with disparate affinities in the order SMD2>SMD4>SMD3>SMD1,
      apparent K d values being 0.44 +/- 0.03, 1.40 +/- 0.16, 8.01 +/- 0.29, and 136.62
      +/- 6.56 uM, respectively. Interestingly, simultaneous determinations of
      biosensor responses and suitable Ca(2+) indicators identified separate Ca(2+)
      sensitivities for their interactions with calmodulin. SMD1-CaM complexes display
      a biphasic Ca(2+) response, representing two distinct species (SMD1 sp1 and SMD1
      sp2) with drastically different Ca(2+) sensitivities. The Ca(2+) sensitivities of
      CaM-SMDs interactions follow the order SMD1sp1>SMD4>SMD2>SMD1sp2>SMD3,
      EC50(Ca(2+)) values being 0.13 +/- 0.02, 0.75 +/- 0.05, 2.38 +/- 0.13, 3.71 +/-
      0.13, and 5.15 +/- 0.25 uM, respectively. These data indicate that calmodulin may
      regulate GPER-dependent signaling at the receptor level through multiple
      interaction sites. FRET biosensors represent a simple method to identify unknown
      calmodulin-binding domains in G protein-coupled receptors and to quantitatively
      assess binding properties.

PMID- 24586951
TI  - Remote control of respiratory neural network by spinal locomotor generators.
AB  - During exercise and locomotion, breathing rate rapidly increases to meet the
      suddenly enhanced oxygen demand. The extent to which direct central interactions
      between the spinal networks controlling locomotion and the brainstem networks
      controlling breathing are involved in this rhythm modulation remains unknown.
      Here, we show that in isolated neonatal rat brainstem-spinal cord preparations,
      the increase in respiratory rate observed during fictive locomotion is associated
      with an increase in the excitability of pre-inspiratory neurons of the parafacial
      respiratory group (pFRG/Pre-I). In addition, this locomotion-induced respiratory
      rhythm modulation is prevented both by bilateral lesion of the pFRG region and by
      blockade of neurokinin 1 receptors in the brainstem. Thus, our results assign
      pFRG/Pre-I neurons a new role as elements of a previously undescribed pathway
      involved in the functional interaction between respiratory and locomotor
      networks, an interaction that also involves a substance P-dependent modulating
      mechanism requiring the activation of neurokinin 1 receptors. This neurogenic
      mechanism may take an active part in the increased respiratory rhythmicity
      produced at the onset and during episodes of locomotion in mammals. 

PMID- 24586952
TI  - Dynamics of an interactive network composed of a bacterial two-component system,
      a transporter and K+ as mediator.
AB  - KdpD and KdpE form a histidine kinase/response regulator system that senses K(+)
      limitation and induces the kdpFABC operon, which encodes a high-affinity K(+)
      uptake complex. To define the primary stimulus perceived by KdpD we focused in
      this study on the dynamics of the Kdp response. Escherichia coli cells were
      subjected to severe K(+) limitation, and all relevant parameters of the Kdp
      response, i.e., levels of kdpFABC transcripts and KdpFABC proteins, as well as
      extra- and intracellular K(+) concentrations, were quantitatively analysed over
      time (0 to 180 min). Unexpectedly, induction of kdpFABC was found to follow a non
      monotonic time-course. To interpret this unusual behaviour, a mathematical model
      that adequately captures the dynamics of the Kdp system was established and used
      for simulations. We found a strong correlation between KdpD/KdpE activation and
      the intracellular K(+) concentration, which is influenced by the uptake of K(+)
      via the KdpFABC complex. Based on these results a model is proposed in which
      KdpD/KdpE phosphorylation is inversely correlated with the intracellular K(+)
      concentration. To corroborate this hypothesis an isogenic mutant that produces a
      defective KdpFABC complex, and the trans-complemented mutant that expresses the
      KtrAB high-affinity K(+) uptake system of Vibrio alginolyticus were
      quantitatively analysed. Experimental data and simulations for the mutants
      consistently support the tight correlation between KdpD/KdpE activation and the
      intracellular K(+) concentration. This study presents a striking example of the
      non-intuitive dynamics of a functional unit comprising signalling proteins and a
      transporter with K(+) as mediator. 

PMID- 24586953
TI  - 3D visualization of the initial Yersinia ruckeri infection route in rainbow trout
      (Oncorhynchus mykiss) by optical projection tomography.
AB  - Despite the fact that enteric redmouth disease (ERM) in farmed rainbow trout is
      one of the most devastating disease problems, little is known about the initial
      route of infection and pathogenicity of the aetiological agent, Yersinia ruckeri.
      In order to determine the initially infected organs, optical projection
      tomography (OPT), a novel three-dimensional (3D) bio-imaging technique, was
      applied. OPT not only enables the visualization of Y. ruckeri on mucosal surfaces
      but also the 3D spatial distribution in whole organs, without sectioning. Rainbow
      trout were infected by bath challenge exposure to 1 * 10(8) CFU/ml of Y. ruckeri
      O1 for 1 hour. Three fish were sampled for OPT and immunohistochemistry (IHC) 1,
      10 and 30 minutes, 1, 3, 6, 12 and 24 hours, as well as 2, 3, 7 and 21 days after
      the start of the infection period. Y. ruckeri was re-isolated from the blood of
      infected fish as early as 1 minute post infection. Both OPT and IHC analysis
      confirmed that the secondary gill lamellae were the only tissues infected at this
      early time point, indicating that Y. ruckeri initially infects gill epithelial
      cells. The experimentally induced infection caused septicemia, and Y. ruckeri was
      found in all examined organs 7 days post infection including the brain, which
      correlated with the peak in mortality. To the best of our knowledge this is the
      first description of Y. ruckeri infection in the brain, which is likely to cause
      encephalitis. This in part could explain the lethality of ERM in rainbow trout.
      Using OPT scanning it was possible to visualize the initial route of entry, as
      well as secondary infection routes along with the proliferation and spread of Y.
      ruckeri, ultimately causing significant mortality in the exposed rainbow trout.
      These results demonstrate that OPT is a state-of-the-art technique capable of
      visualizing pathogenesis at high resolution.

PMID- 24586954
TI  - SnapShot-Seq: a method for extracting genome-wide, in vivo mRNA dynamics from a
      single total RNA sample.
AB  - mRNA synthesis, processing, and destruction involve a complex series of molecular
      steps that are incompletely understood. Because the RNA intermediates in each of
      these steps have finite lifetimes, extensive mechanistic and dynamical
      information is encoded in total cellular RNA. Here we report the development of
      SnapShot-Seq, a set of computational methods that allow the determination of in
      vivo rates of pre-mRNA synthesis, splicing, intron degradation, and mRNA decay
      from a single RNA-Seq snapshot of total cellular RNA. SnapShot-Seq can detect in
      vivo changes in the rates of specific steps of splicing, and it provides genome
      wide estimates of pre-mRNA synthesis rates comparable to those obtained via
      labeling of newly synthesized RNA. We used SnapShot-Seq to investigate the
      origins of the intrinsic bimodality of metazoan gene expression levels, and our
      results suggest that this bimodality is partly due to spillover of
      transcriptional activation from highly expressed genes to their poorly expressed
      neighbors. SnapShot-Seq dramatically expands the information obtainable from a
      standard RNA-Seq experiment. 

PMID- 24586955
TI  - Modulation of innate immune responses by influenza-specific ovine polyclonal
      antibodies used for prophylaxis.
AB  - In the event of a novel influenza A virus pandemic, prophylaxis mediated by
      antibodies provides an adjunct control option to vaccines and antivirals. This
      strategy is particularly pertinent to unvaccinated populations at risk during the
      lag time to produce and distribute an effective vaccine. Therefore, development
      of effective prophylactic therapies is of high importance. Although previous
      approaches have used systemic delivery of monoclonal antibodies or convalescent
      sera, available supply is a serious limitation. Here, we have investigated
      intranasal delivery of influenza-specific ovine polyclonal IgG antibodies for
      their efficacy against homologous influenza virus challenge in a mouse model.
      Both influenza-specific IgG and F(ab')2 reduced clinical scores, body weight loss
      and lung viral loads in mice treated 1 hour before virus exposure. Full
      protection from disease was also observed when antibody was delivered up to 3
      days prior to virus infection. Furthermore, effective prophylaxis was independent
      of a strong innate immune response. This strategy presents a further option for
      prophylactic intervention against influenza A virus using ruminants to generate a
      bulk supply that could potentially be used in a pandemic setting, to slow virus
      transmission and reduce morbidity associated with a high cytokine phenotype. 

PMID- 24586956
TI  - Culture of primary ciliary dyskinesia epithelial cells at air-liquid interface
      can alter ciliary phenotype but remains a robust and informative diagnostic aid.
AB  - BACKGROUND: The diagnosis of primary ciliary dyskinesia (PCD) requires the
      analysis of ciliary function and ultrastructure. Diagnosis can be complicated by
      secondary effects on cilia such as damage during sampling, local inflammation or
      recent infection. To differentiate primary from secondary abnormalities, re
      analysis of cilia following culture and re-differentiation of epithelial cells at
      an air-liquid interface (ALI) aids the diagnosis of PCD. However changes in
      ciliary beat pattern of cilia following epithelial cell culture has previously
      been described, which has brought the robustness of this method into question.
      This is the first systematic study to evaluate ALI culture as an aid to diagnosis
      of PCD in the light of these concerns. METHODS: We retrospectively studied
      changes associated with ALI-culture in 158 subjects referred for diagnostic
      testing at two PCD centres. Ciliated nasal epithelium (PCD n = 54; non-PCD n 
      111) was analysed by high-speed digital video microscopy and transmission
      electron microscopy before and after culture. RESULTS: Ciliary function was
      abnormal before and after culture in all subjects with PCD; 21 PCD subjects had a
      combination of static and uncoordinated twitching cilia, which became completely
      static following culture, a further 9 demonstrated a decreased ciliary beat
      frequency after culture. In subjects without PCD, secondary ciliary dyskinesia
      was reduced. CONCLUSIONS: The change to ciliary phenotype in PCD samples
      following cell culture does not affect the diagnosis, and in certain cases can
      assist the ability to identify PCD cilia.

PMID- 24586957
TI  - Molecular stress responses to nano-sized zero-valent iron (nZVI) particles in the
      soil bacterium Pseudomonas stutzeri.
AB  - Nanotoxicological studies were performed in vitro using the common soil bacterium
      Pseudomonas stutzeri to assess the potentially toxic impact of commercial nano
      sized zero-valent iron (nZVI) particles, which are currently used for
      environmental remediation projects. The phenotypic response of P. stutzeri to
      nZVI toxicity includes an initial insult to the cell wall, as evidenced by TEM
      micrographs. Transcriptional analyses using genes of particular relevance in
      cellular activity revealed that no significant changes occurred among the
      relative expression ratios of narG, nirS, pykA or gyrA following nZVI exposure;
      however, a significant increase in katB expression was indicative of nZVI-induced
      oxidative stress in P. stutzeri. A proteomic approach identified two major
      defence mechanisms that occurred in response to nZVI exposure: a downregulation
      of membrane proteins and an upregulation of proteins involved in reducing
      intracellular oxidative stress. These biomarkers served as early indicators of
      nZVI response in this soil bacterium, and may provide relevant information for
      environmental hazard assessment. 

PMID- 24586958
TI  - Inhibition of TGFbeta signaling increases direct conversion of fibroblasts to
      induced cardiomyocytes.
AB  - Recent studies have been successful at utilizing ectopic expression of
      transcription factors to generate induced cardiomyocytes (iCMs) from fibroblasts,
      albeit at a low frequency in vitro. This work investigates the influence of small
      molecules that have been previously reported to improve differentiation to
      cardiomyocytes as well as reprogramming to iPSCs in conjunction with ectopic
      expression of the transcription factors Hand2, Nkx2.5, Gata4, Mef2C, and Tbx5 on
      the conversion to functional iCMs. We utilized a reporter system in which the
      calcium indicator GCaMP is driven by the cardiac Troponin T promoter to quantify
      iCM yield. The TGFbeta inhibitor, SB431542 (SB), was identified as a small
      molecule capable of increasing the conversion of both mouse embryonic fibroblasts
      and adult cardiac fibroblasts to iCMs up to ~5 fold. Further characterization
      revealed that inhibition of TGFbeta by SB early in the reprogramming process led
      to the greatest increase in conversion of fibroblasts to iCMs in a dose
      responsive manner. Global transcriptional analysis at Day 3 post-induction of the
      transcription factors revealed an increased expression of genes associated with
      the development of cardiac muscle in the presence of SB compared to the vehicle
      control. Incorporation of SB in the reprogramming process increases the
      efficiency of iCM generation, one of the major goals necessary to enable the use
      of iCMs for discovery-based applications and for the clinic. 

PMID- 24586959
TI  - Adaptive optics-assisted identification of preferential erythrocyte aggregate
      pathways in the human retinal microvasculature.
AB  - PURPOSE: To characterize human parafoveal blood flow using adaptive optics
      scanning laser ophthalmoscopy (AO-SLO). METHODS: In 5 normal subjects,
      erythrocyte aggregate distributions were analyzed on 3 different days.
      Erythrocyte aggregates were described as a "dark tail" in AO-SLO. The
      characteristics of the pathways with dark tail flow in the parafovea were
      measured. Additionally, the tendency for dark tail flow before and after
      bifurcations was analyzed to study the blood flow in detail. RESULTS: Average
      velocity in parent vessels with dark tail flow was 1.30+/-0.27 mm/s. Average
      velocity in daughter vessels with dark tail flow was 1.12+/-0.25 mm/s, and the
      average velocity of plasma gaps in daughter vessels without dark tail flow was
      0.64+/-0.11 mm/s. Downstream from the bifurcations, the velocity in vessels with
      dark tail flow was higher than that in those without it (p<0.001), and the
      branching angles of vessels with dark tail flow were smaller than those of
      vessels without it (p<0.001). CONCLUSIONS: Images from the AO-SLO noninvasively
      revealed pathways with and without dark tail flow in the human parafovea.
      Pathways with dark tail flow in the daughter vessels generally had faster flow
      and smaller bifurcation angles than daughter vessels without dark tail flow.
      Thus, AO-SLO is an instructive tool for analyzing retinal microcirculatory
      hemodynamics.

PMID- 24586960
TI  - A selected core microbiome drives the early stages of three popular italian
      cheese manufactures.
AB  - Mozzarella (M), Grana Padano (GP) and Parmigiano Reggiano (PR) are three of the
      most important traditional Italian cheeses. In the three cheese manufactures the
      initial fermentation is carried out by adding natural whey cultures (NWCs)
      according to a back-slopping procedure. In this study, NWCs and the corresponding
      curds from M, GP and PR manufactures were analyzed by culture-independent
      pyrosequencing of the amplified V1-V3 regions of the 16S rRNA gene, in order to
      provide insights into the microbiota involved in the curd acidification.
      Moreover, culture-independent high-throughput sequencing of lacS gene amplicons
      was carried out to evaluate the biodiversity occurring within the S. thermophilus
      species. Beta diversity analysis showed a species-based differentiation between
      GP-PR and M manufactures indicating differences between the preparations.
      Nevertheless, all the samples shared a naturally-selected core microbiome, that
      is involved in the curd acidification. Type-level variability within S.
      thermophilus species was also found and twenty-eight lacS gene sequence types
      were identified. Although lacS gene did not prove variable enough within S.
      thermophilus species to be used for quantitative biotype monitoring, the
      possibility of using non rRNA targets for quantitative biotype identification in
      food was highlighted. 

PMID- 24586961
TI  - Diversity of rumen bacteria in canadian cervids.
AB  - Interest in the bacteria responsible for the breakdown of lignocellulosic
      feedstuffs within the rumen has increased due to their potential utility in
      industrial applications. To date, most studies have focused on bacteria from
      domesticated ruminants. We have expanded the knowledge of the microbial ecology
      of ruminants by examining the bacterial populations found in the rumen of non
      domesticated ruminants found in Canada. Next-generation sequencing of 16S rDNA
      was employed to characterize the liquid and solid-associated bacterial
      communities in the rumen of elk (Cervus canadensis), and white tailed deer
      (Odocoileus virginianus). Despite variability in the microbial populations
      between animals, principle component and weighted UniFrac analysis indicated that
      bacterial communities in the rumen of elk and white tail deer are distinct.
      Populations clustered according to individual host animal and not the association
      with liquid or solid phase of the rumen contents. In all instances, Bacteroidetes
      and Firmicutes were the dominant bacterial phyla, although the relative abundance
      of these differed among ruminant species and between phases of rumen digesta,
      respectively. In the elk samples Bacteroidetes were more predominant in the
      liquid phase whereas Firmicutes was the most prevalent phyla in the solid digesta
      (P = 1*10(-5)). There were also statistically significant differences in the
      abundance of OTUs classified as Fibrobacteres (P = 5*10(-3)) and Spirochaetes (P
      = 3*10(-4)) in the solid digesta of the elk samples. We identified a number of
      OTUs that were classified as phylotypes not previously observed in the rumen
      environment. Our results suggest that although the bacterial diversity in wild
      North American ruminants shows overall similarities to domesticated ruminants, we
      observed a number of OTUs not previously described. Previous studies primarily
      focusing on domesticated ruminants do not fully represent the microbial diversity
      of the rumen and studies focusing on non-domesticated ruminants should be
      expanded.

PMID- 24586962
TI  - Sensory arsenal on the stinger of the parasitoid jewel wasp and its possible role
      in identifying cockroach brains.
AB  - The parasitoid jewel wasp uses cockroaches as live food supply for its developing
      larva. To this end, the adult wasp stings a cockroach and injects venom directly
      inside its brain, turning the prey into a submissive 'zombie'. Here, we
      characterize the sensory arsenal on the wasp's stinger that enables the wasp to
      identify the brain target inside the cockroach's head. An electron microscopy
      study of the stinger reveals (a) cuticular depressions innervated by a single
      mechanosensory neuron, which are presumably campaniform sensilla; and (b) dome
      shaped structures innervated by a single mechanosensory neuron and 4-5
      chemosensory neurons, which are presumably contact-chemoreceptive sensilla.
      Extracellular electrophysiological recordings from stinger afferents show
      increased firing rate in response to mechanical stimulation with agarose. This
      response is direction-selective and depends upon the concentration (density) of
      the agarose, such that the most robust response is evoked when the stinger is
      stimulated in the distal-to-proximal direction (concomitant with the penetration
      during the natural stinging behavior) and penetrating into relatively hard (0.75%
      2.5%) agarose pellets. Accordingly, wasps demonstrate a normal stinging behavior
      when presented with cockroaches in which the brain was replaced with a hard
      (2.5%) agarose pellet. Conversely, wasps demonstrate a prolonged stinging
      behavior when the cockroach brain was either removed or replaced by a soft (0.5%)
      agarose pellet, or when stinger sensory organs were ablated prior to stinging. We
      conclude that the parasitoid jewel wasp uses at least mechanosensory inputs from
      its stinger to identify the brain within the head capsule of the cockroach prey. 

PMID- 24586964
TI  - Significant increase in ecosystem C can be achieved with sustainable forest
      management in subtropical plantation forests.
AB  - Subtropical planted forests are rapidly expanding. They are traditionally managed
      for intensive, short-term goals that often lead to long-term yield decline and
      reduced carbon sequestration capacity. Here we show how it is possible to
      increase and sustain carbon stored in subtropical forest plantations if
      management is switched towards more sustainable forestry. We first conducted a
      literature review to explore possible management factors that contribute to the
      potentials in ecosystem C in tropical and subtropical plantations. We found that
      broadleaves plantations have significantly higher ecosystem C than conifer
      plantations. In addition, ecosystem C increases with plantation age, and reaches
      a peak with intermediate stand densities of 1500-2500 trees ha-1. We then used
      the FORECAST model to simulate the regional implications of switching from
      traditional to sustainable management regimes, using Chinese fir (Cunninghamia
      lanceolata) plantations in subtropical China as a study case. We randomly
      simulated 200 traditional short-rotation pure stands and 200 sustainably-managed
      mixed Chinese fir--Phoebe bournei plantations, for 120 years. Our results showed
      that mixed, sustainably-managed plantations have on average 67.5% more ecosystem
      C than traditional pure conifer plantations. If all pure plantations were
      gradually transformed into mixed plantations during the next 10 years, carbon
      stocks could rise in 2050 by 260.22 TgC in east-central China. Assuming similar
      differences for temperate and boreal plantations, if sustainable forestry
      practices were applied to all new forest plantation types in China, stored carbon
      could increase by 1,482.80 TgC in 2050. Such an increase would be equivalent to a
      yearly sequestration rate of 40.08 TgC yr-1, offsetting 1.9% of China's annual
      emissions in 2010. More importantly, this C increase can be sustained in the long
      term through the maintenance of higher amounts of soil organic carbon and the
      production of timber products with longer life spans.

PMID- 24586963
TI  - Genome wide association mapping of grain arsenic, copper, molybdenum and zinc in
      rice (Oryza sativa L.) grown at four international field sites.
AB  - The mineral concentrations in cereals are important for human health, especially
      for individuals who consume a cereal subsistence diet. A number of elements, such
      as zinc, are required within the diet, while some elements are toxic to humans,
      for example arsenic. In this study we carry out genome-wide association (GWA)
      mapping of grain concentrations of arsenic, copper, molybdenum and zinc in brown
      rice using an established rice diversity panel of ~ 300 accessions and 36.9 k
      single nucleotide polymorphisms (SNPs). The study was performed across five
      environments: one field site in Bangladesh, one in China and two in the US, with
      one of the US sites repeated over two years. GWA mapping on the whole dataset and
      on separate subpopulations of rice revealed a large number of loci significantly
      associated with variation in grain arsenic, copper, molybdenum and zinc.
      Seventeen of these loci were detected in data obtained from grain cultivated in
      more than one field location, and six co-localise with previously identified
      quantitative trait loci. Additionally, a number of candidate genes for the uptake
      or transport of these elements were located near significantly associated SNPs
      (within 200 kb, the estimated global linkage disequilibrium previously employed
      in this rice panel). This analysis highlights a number of genomic regions and
      candidate genes for further analysis as well as the challenges faced when mapping
      environmentally-variable traits in a highly genetically structured diversity
      panel.

PMID- 24586965
TI  - Molecular cloning of a novel glucuronokinase/putative pyrophosphorylase from
      zebrafish acting in an UDP-glucuronic acid salvage pathway.
AB  - In animals, the main precursor for glycosaminoglycan and furthermore proteoglycan
      biosynthesis, like hyaluronic acid, is UDP-glucuronic acid, which is synthesized
      via the nucleotide sugar oxidation pathway. Mutations in this pathway cause
      severe developmental defects (deficiency in the initiation of heart valve
      formation). In plants, UDP-glucuronic acid is synthesized via two independent
      pathways. Beside the nucleotide sugar oxidation pathway, a second minor route to
      UDP-glucuronic acid exist termed the myo-inositol oxygenation pathway. Within
      this myo-inositol is ring cleaved into glucuronic acid, which is subsequently
      converted to UDP-glucuronic acid by glucuronokinase and UDP-sugar
      pyrophosphorylase. Here we report on a similar, but bifunctional enzyme from
      zebrafish (Danio rerio) which has glucuronokinase/putative pyrophosphorylase
      activity. The enzyme can convert glucuronic acid into UDP-glucuronic acid,
      required for completion of the alternative pathway to UDP-glucuronic acid via myo
      inositol and thus establishes a so far unknown second route to UDP-glucuronic
      acid in animals. Glucuronokinase from zebrafish is a member of the GHMP-kinase
      superfamily having unique substrate specificity for glucuronic acid with a Km of
      31 +/- 8 uM and accepting ATP as the only phosphate donor (Km: 59 +/- 9 uM). UDP
      glucuronic acid pyrophosphorylase from zebrafish has homology to bacterial
      nucleotidyltransferases and requires UTP as nucleosid diphosphate donor. Genes
      for bifunctional glucuronokinase and putative UDP-glucuronic acid
      pyrophosphorylase are conserved among some groups of lower animals, including
      fishes, frogs, tunicates, and polychaeta, but are absent from mammals. The
      existence of a second pathway for UDP-glucuronic acid biosynthesis in zebrafish
      likely explains some previous contradictory finding in jekyll/ugdh zebrafish
      developmental mutants, which showed residual glycosaminoglycans and proteoglycans
      in knockout mutants of UDP-glucose dehydrogenase.

PMID- 24586966
TI  - Assessing the exoproteome of marine bacteria, lesson from a RTX-toxin abundantly
      secreted by Phaeobacter strain DSM 17395.
AB  - Bacteria from the Roseobacter clade are abundant in surface marine ecosystems as
      over 10% of bacterial cells in the open ocean and 20% in coastal waters belong to
      this group. In order to document how these marine bacteria interact with their
      environment, we analyzed the exoproteome of Phaeobacter strain DSM 17395. We grew
      the strain in marine medium, collected the exoproteome and catalogued its content
      with high-throughput nanoLC-MS/MS shotgun proteomics. The major component
      represented 60% of the total protein content but was refractory to either
      classical proteomic identification or proteogenomics. We de novo sequenced this
      abundant protein with high-resolution tandem mass spectra which turned out being
      the 53 kDa RTX-toxin ZP_02147451. It comprised a peptidase M10 serralysin domain.
      We explained its recalcitrance to trypsin proteolysis and proteomic
      identification by its unusual low number of basic residues. We found this is a
      conserved trait in RTX-toxins from Roseobacter strains which probably explains
      their persistence in the harsh conditions around bacteria. Comprehensive analysis
      of exoproteomes from environmental bacteria should take into account this
      proteolytic recalcitrance. 

PMID- 24586967
TI  - The role of surgery in global health: analysis of United States inpatient
      procedure frequency by condition using the Global Burden of Disease 2010
      framework.
AB  - BACKGROUND: The role of surgical care in promoting global health is the subject
      of much debate. The Global Burden of Disease 2010 study (GBD 2010) offers a new
      opportunity to consider where surgery fits amongst global health priorities. The
      GBD 2010 reinforces the DALY as the preferred methodology for determining the
      relative contribution of disease categories to overall global burden of disease
      without reference to the likelihood of each category requiring surgery. As such,
      we hypothesize that the GBD framework underestimates the role of surgery in
      addressing the global burden of disease. METHODS AND FINDINGS: We compiled
      International Classification of Diseases, Version 9, codes from the United States
      Nationwide Inpatient Sample from 2010. Using the primary diagnosis code for each
      hospital admission, we aggregated admissions into GBD 2010 disease sub
      categories. We queried each hospitalization for a major operation to determine
      the frequency of admitted patients whose care required surgery. Major operation
      was defined according to the Agency for Healthcare Research and Quality (AHRQ).
      In 2010, 10 million major inpatient operations were performed in the United
      States, associated with 28.6% of all admissions. Major operations were performed
      in every GBD disease subcategory (range 0.2%-84.0%). The highest frequencies of
      operation were in the subcategories of Musculoskeletal (84.0%), Neoplasm (61.4%),
      and Transport Injuries (43.2%). There was no disease subcategory that always
      required an operation; nor was there any disease subcategory that never required
      an operation. CONCLUSIONS: Surgical care cuts across the entire spectrum of GBD
      disease categories, challenging dichotomous traditional classifications of
      'surgical' versus 'nonsurgical' diseases. Current methods of measuring global
      burden of disease do not reflect the fundamental role operative intervention
      plays in the delivery of healthcare services. Novel methodologies should be aimed
      at understanding the integration of surgical services into health systems to
      address the global burden of disease.

PMID- 24586968
TI  - Regulation of Drosophila eye development by the transcription factor Sine oculis.
AB  - Homeodomain transcription factors of the Sine oculis (SIX) family direct multiple
      regulatory processes throughout the metazoans. Sine oculis (So) was first
      characterized in the fruit fly Drosophila melanogaster, where it is both
      necessary and sufficient for eye development, regulating cell survival,
      proliferation, and differentiation. Despite its key role in development, only a
      few direct targets of So have been described previously. In the current study, we
      aim to expand our knowledge of So-mediated transcriptional regulation in the
      developing Drosophila eye using ChIP-seq to map So binding regions throughout the
      genome. We find 7,566 So enriched regions (peaks), estimated to map to 5,952
      genes. Using overlap between the So ChIP-seq peak set and genes that are
      differentially regulated in response to loss or gain of so, we identify putative
      direct targets of So. We find So binding enrichment in genes not previously known
      to be regulated by So, including genes that encode cell junction proteins and
      signaling pathway components. In addition, we analyze a subset of So-bound novel
      genes in the eye, and find eight genes that have previously uncharacterized eye
      phenotypes and may be novel direct targets of So. Our study presents a greatly
      expanded list of candidate So targets and serves as basis for future studies of
      So-mediated gene regulation in the eye. 

PMID- 24586969
TI  - Interspecific Competition between Aedes albopictus and A. sierrensis: potential
      for Competitive Displacement in the Western United States.
AB  - The Asian tiger mosquito, Aedes albopictus, was first detected in North America
      twenty five years ago. It utilizes water-holding container habitats as immature
      development sites, and has rapidly spread throughout the eastern United States.
      Aedes albopictus has occasionally been detected in the western United States, but
      until recently no established populations of A. albopictus were reported. The
      western tree-hole mosquito, Aedes sierrensis, is the most common tree-hole
      mosquito throughout the western United States, and is expected to more frequently
      encounter A. albopictus. In this study, competition between A. albopictus from
      the eastern United States and A. sierrensis from the western United States was
      tested in order to better understand the potential for either competitive
      displacement of A. sierrensis by A. albopictus or competitive resistance of A.
      sierrensis to A. albopictus. Varying densities of each species were reared with
      limited resources in a response surface design. Consistent with a prior study, we
      found that A. albopictus was clearly a superior larval competitor than A.
      sierrensis. Aedes sierrensis lambda' (finite rate of increase) decreased with
      increasing A. albopictus density, but in contrast, A. albopictus lambda' actually
      increased with increasing A. sierrensis density; a result that was not reflected
      by individual fitness parameters. These results indicate that A. sierrensis will
      not be an effective barrier to A. albopictus invasion into tree-holes in the
      western United States. 

PMID- 24586970
TI  - Opposite reactivity of meningeal versus cortical microvessels to the nitric oxide
      donor glyceryl trinitrate evaluated in vivo with two-photon imaging.
AB  - Vascular changes underlying headache in migraine patients induced by Glyceryl
      trinitrate (GTN) were previously studied with various imaging techniques. Despite
      the long history of medical and experimental use of GTN, its effects on the brain
      vasculature are still poorly understood presumably due to low spatial resolution
      of the imaging modalities used so far. We took advantage of the micrometer-scale
      vertical resolution of two-photon microscopy to differentiate between the
      vasodynamic effects of GTN on meningeal versus cortical vessels imaged
      simultaneously in anesthetized rats through either thinned skull or glass-sealed
      cranial window. Intermediate and small calibre vessels were visualized in vivo by
      imaging intravascular fluorescent dextran, and detection of blood flow direction
      allowed identification of individual arterioles and venules. We found that i.p.
      injected GTN induced a transient constriction of meningeal arterioles, while
      their cortical counterparts were, in contrast, dilated. These opposing effects of
      GTN were restricted to arterioles, whereas the effects on venules were
      insignificant. Interestingly, the NO synthase inhibitor L-NAME did not affect the
      diameter of meningeal vessels but induced a constriction of cortical vessels. The
      different cellular environment in cortex versus meninges as well as distinct
      vessel wall anatomical features probably play crucial role in the observed
      phenomena. These findings highlight differential region- and vessel-type-specific
      effects of GTN on cranial vessels, and may implicate new vascular mechanisms of
      NO-mediated primary headaches. 

PMID- 24586971
TI  - Using multivariate regression model with least absolute shrinkage and selection
      operator (LASSO) to predict the incidence of Xerostomia after intensity-modulated
      radiotherapy for head and neck cancer.
AB  - PURPOSE: The aim of this study was to develop a multivariate logistic regression
      model with least absolute shrinkage and selection operator (LASSO) to make valid
      predictions about the incidence of moderate-to-severe patient-rated xerostomia
      among head and neck cancer (HNC) patients treated with IMRT. METHODS AND
      MATERIALS: Quality of life questionnaire datasets from 206 patients with HNC were
      analyzed. The European Organization for Research and Treatment of Cancer QLQ
      H&N35 and QLQ-C30 questionnaires were used as the endpoint evaluation. The
      primary endpoint (grade 3(+) xerostomia) was defined as moderate-to-severe
      xerostomia at 3 (XER3m) and 12 months (XER12m) after the completion of IMRT.
      Normal tissue complication probability (NTCP) models were developed. The optimal
      and suboptimal numbers of prognostic factors for a multivariate logistic
      regression model were determined using the LASSO with bootstrapping technique.
      Statistical analysis was performed using the scaled Brier score, Nagelkerke R(2),
      chi-squared test, Omnibus, Hosmer-Lemeshow test, and the AUC. RESULTS: Eight
      prognostic factors were selected by LASSO for the 3-month time point: Dmean-c,
      Dmean-i, age, financial status, T stage, AJCC stage, smoking, and education. Nine
      prognostic factors were selected for the 12-month time point: Dmean-i, education,
      Dmean-c, smoking, T stage, baseline xerostomia, alcohol abuse, family history,
      and node classification. In the selection of the suboptimal number of prognostic
      factors by LASSO, three suboptimal prognostic factors were fine-tuned by Hosmer
      Lemeshow test and AUC, i.e., Dmean-c, Dmean-i, and age for the 3-month time
      point. Five suboptimal prognostic factors were also selected for the 12-month
      time point, i.e., Dmean-i, education, Dmean-c, smoking, and T stage. The overall
      performance for both time points of the NTCP model in terms of scaled Brier
      score, Omnibus, and Nagelkerke R(2) was satisfactory and corresponded well with
      the expected values. CONCLUSIONS: Multivariate NTCP models with LASSO can be used
      to predict patient-rated xerostomia after IMRT.

PMID- 24586972
TI  - Floral evolution of Philodendron subgenus Meconostigma (Araceae).
AB  - Elucidating the evolutionary patterns of flower and inflorescence structure is
      pivotal to understanding the phylogenetic relationships of Angiosperms as a
      whole. The inflorescence morphology and anatomy of Philodendron subgenus
      Meconostigma, belonging to the monocot family Araceae, has been widely studied
      but the evolutionary relationships of subgenus Meconostigma and the evolution of
      its flower characters have hitherto remained unclear. This study examines
      gynoecium evolution in subgenus Meconostigma in the context of an estimated
      molecular phylogeny for all extant species of subgenus Meconostigma and analysis
      of ancestral character reconstructions of some gynoecial structures. The
      phylogenetic reconstructions of all extant Meconostigma species were conducted
      under a maximum likelihood approach based on the sequences of two chloroplast
      (trnk and matK) and two nuclear (ETS and 18S) markers. This topology was used to
      reconstruct the ancestral states of seven floral characters and to elucidate
      their evolutionary pattern in the Meconostigma lineage. Our phylogeny shows that
      Meconostigma is composed of two major clades, one comprising two Amazonian
      species and the other all the species from the Atlantic Forest and Cerrado biomes
      with one Amazonian species. The common ancestor of the species of subgenus
      Meconostigma probably possessed short stylar lobes, long stylar canals, a stylar
      body, a vascular plexus in the gynoecium and druses in the stylar parenchyma but
      it is uncertain whether raphide inclusions were present in the parenchyma. The
      ancestral lineage also probably possessed up to 10 ovary locules. The evolution
      of these characters seems to have occurred independently in some lineages. We
      propose that the morphological and anatomical diversity observed in the gynoecial
      structures of subgenus Meconostigma is the result of an ongoing process of fusion
      of floral structures leading to a reduction of energy wastage and increase in
      stigmatic surface. 

PMID- 24586973
TI  - Prevalence, incidence and determinants of herpes simplex virus type 2 infection
      among HIV-seronegative women at high-risk of HIV infection: a prospective study
      in Beira, Mozambique.
AB  - OBJECTIVES: To estimate the prevalence, incidence and determinants of herpes
      simplex type 2 (HSV-2) infection, and associations between HSV-2 and incident HIV
      infection, among women at higher risk for HIV infection in Beira, Mozambique.
      METHODS: Between 2009 and 2012, 411 women aged 18-35 years at higher risk of HIV
      acquisition (defined as having had two or more sexual partners in the month prior
      to study enrollment) were enrolled and followed monthly for one year. At each
      study visit, they were counseled, interviewed, and tested for HSV-2 and HIV
      antibodies. RESULTS: The HSV-2 prevalence at baseline was 60.6% (95% CI: 55.7% 
      65.4%). Increasing age (aOR = 2.94, 95% CI: 1.74-4.97, P<0.001 and aOR = 3.39,
      95% CI: 1.58-7.29, P = 0.002 for age groups of 21-24 and 25-35 years old
      respectively), lower educational level (aOR = 1.81, 95% CI: 1.09-3.02, P =
      0.022), working full time (aOR = 8.56, 95% CI: 1.01-72.53, P = 0.049) and having
      practiced oral sex (aOR = 3.02, 95% CI: 1.16-7.89, P = 0.024) were strongly
      associated with prevalent HSV-2 infection. Thirty one participants seroconverted
      for HSV-2 (20.5%; 95% CI: 14.4% -27.9%) and 22 for HIV during the study period.
      The frequency of vaginal sex with a casual partner using a condom in the last 7
      days was independently associated with incident HSV-2 infection (aOR = 1.91, 95%
      CI: 1.05-3.47, P = 0.034). Positive HSV-2 serology at baseline was not
      significantly associated with risk of subsequent HIV seroconversion. CONCLUSIONS:
      Young women engaging in risky sexual behaviors in Beira had high prevalence and
      incidence of HSV-2 infection. Improved primary HSV-2 control strategies are
      urgently needed in Beira.

PMID- 24586974
TI  - Changes in nephritogenic serum galactose-deficient IgA1 in IgA nephropathy
      following tonsillectomy and steroid therapy.
AB  - BACKGROUND: Recent studies have shown that galactose-deficient IgA1 (GdIgA1) has
      an important role in the pathogenesis of IgA nephropathy (IgAN). Although
      emerging data suggest that serum GdIgA1 can be a useful non-invasive IgAN
      biomarker, the localization of nephritogenic GdIgA1-producing B cells remains
      unclear. Recent clinical and experimental studies indicate that immune activation
      tonsillar toll-like receptor (TLR) 9 may be involved in the pathogenesis of IgAN.
      Here we assessed the possibility of GdIgA1 production in the palatine tonsils in
      IgAN patients. METHODS: We assessed changes in serum GdIgA1 levels in IgAN
      patients with clinical remission of hematuria and proteinuria following combined
      tonsillectomy and steroid pulse therapy. Further, the association between
      clinical outcome and tonsillar TLR9 expression was evaluated. RESULTS: Patients
      (n = 37) were divided into two groups according to therapy response. In one
      group, serum GdIgA1 levels decreased after tonsillectomy (59%) alone, whereas in
      the other group most levels only decreased after the addition of steroid pulse
      therapy to tonsillectomy (41%). The former group showed significantly higher
      tonsillar TLR9 expression and better improvement in hematuria immediately after
      tonsillectomy than the latter group. CONCLUSIONS: The present study indicates
      that the palatine tonsils are probably a major sites of GdIgA1-producing cells.
      However, in some patients these cells may propagate to other lymphoid organs,
      which may partially explain the different responses observed to tonsillectomy
      alone. These findings help to clarify some of the clinical observations in the
      management of IgAN, and may highlight future directions for research.

PMID- 24586978
TI  - Imaging and identification of waterborne parasites using a chip-scale microscope.
AB  - We demonstrate a compact portable imaging system for the detection of waterborne
      parasites in resource-limited settings. The previously demonstrated sub-pixel
      sweeping microscopy (SPSM) technique is a lens-less imaging scheme that can
      achieve high-resolution (<1 um) bright-field imaging over a large field-of-view
      (5.7 mm*4.3 mm). A chip-scale microscope system, based on the SPSM technique, can
      be used for automated and high-throughput imaging of protozoan parasite cysts for
      the effective diagnosis of waterborne enteric parasite infection. We successfully
      imaged and identified three major types of enteric parasite cysts, Giardia,
      Cryptosporidium, and Entamoeba, which can be found in fecal samples from infected
      patients. We believe that this compact imaging system can serve well as a
      diagnostic device in challenging environments, such as rural settings or
      emergency outbreaks. 

PMID- 24586979
TI  - Growth development of French children born after in vitro maturation.
AB  - BACKGROUND: Several lines of evidence indicate that immature oocyte retrieval and
      subsequent in vitro maturation (IVM) without ovarian stimulation may be a
      reliable option in assisted reproductive technologies (ART). However, few outcome
      data are available for children born following this technique. OBJECTIVE: We
      assessed height and weight development of French children conceived after IVM.
      METHODS: All children conceived after IVM at Antoine Beclere Hospital (Clamart,
      France) and born between June 2003 and October 2008 (n = 38) were included in a
      prospective cohort study and compared with a control group of children conceived
      by ICSI without IVM, matched for maternal age, gestational age and singleton/twin
      pregnancies. Follow-up included clinical examination at one year and a
      questionnaire completed by parents when the children were two years old (97%
      follow-up rate). RESULTS: No statistical differences between IVM and control
      groups were found for boys. Mean weight, height and head circumference at birth
      were significantly greater for IVM than for ICSI girls (3.236 kg vs 2.701 kg (p =
      0.03); 49 cm vs 47 cm (p = 0.01) and 34 cm vs 33 cm (p = 0.04), respectively). At
      one year, IVM girls remained heavier (mean weight 10.2 kg vs 8.6 kg (p = 0.001))
      and taller (76 cm vs 73 cm (p = 0.03)), and there was a two-point difference in
      BMI between the two groups of girls (18 vs 16 (p = 0.01)). CONCLUSION: Our
      results in girls born after IVM should be interpreted with caution. It remains
      unclear whether the observed sexual dimorphism is due to IVM technology or to
      maternal characteristics such as underlying infertility in patients with
      polycystic ovary syndrome (PCOS). Further monitoring of the outcomes of these
      infants is required.

PMID- 24586981
TI  - Molecular epidemiology and antimicrobial susceptibility of clinical
      Staphylococcus aureus from healthcare institutions in Ghana.
AB  - The objective of this study was to determine the antimicrobial susceptibility
      patterns and clonal diversity of clinical Staphylococcus aureus isolates from
      Ghana. A total of 308 S. aureus isolates from six healthcare institutions located
      across Northern, Central and Southern Ghana were characterized by antibiotyping,
      spa typing and PCR detection of Panton Valentine leukocin (PVL) genes.
      Methicillin-resistant S. aureus (MRSA) were confirmed by PCR detection of mecA
      gene and further characterized by SCCmec and multi-locus sequence typing (MLST).
      The prevalence of antimicrobial resistance was below 5% for all agents tested
      except for penicillin (97%), tetracycline (42%) and erythromycin (6%). Ninety-one
      spa types were found, with t355 (ST152, 19%), t084 (ST15, 12%) and t314 (ST121,
      6%) being the most frequent types. Based on established associations between spa
      and MLST types, isolates were assigned to 16 clonal complexes (CCs): CC152 (n =
      78), CC15 (n = 57), CC121 (n = 39), CC8 (n = 36), CC5 (n = 33), CC1 (n = 29),
      CC45 (n = 9), CC88 (n = 8), CC30 (n = 4), CC9 (n = 3), CC25 (n = 2), CC97 (n = 2)
      CC20 (n = 2), CC707 (n = 2), CC7 (n = 3) and CC522 (n = 1). Most isolates (60%)
      were PVL-positive, especially those belonging to ST152, ST121, ST5, ST15, ST1,
      ST8, and ST88. Nine (3%) isolates were MRSA belonging to seven distinct clones:
      ST88-IV (n = 2), ST250-I (n = 2), ST8-IV (n = 1), ST72-V (n = 1), ST789-IV (n =
      1), ST2021-V (n = 1), and ST239-III (n = 1). The study confirmed a high frequency
      of PVL-positive S. aureus in Africa, low prevalence of antimicrobial resistance
      and high diversity of MRSA lineages in Ghana compared to developed countries and
      other African countries. The detection of known pandemic MRSA clones in the
      absence of routine MRSA identification in most Ghanaian clinical microbiology
      laboratories calls for capacity building to strengthen surveillance and prevent
      spread of these clones.

PMID- 24586980
TI  - IL-17A signaling in colonic epithelial cells inhibits pro-inflammatory cytokine
      production by enhancing the activity of ERK and PI3K.
AB  - Our previous data suggested that IL-17A contributes to the inhibition of Th1 cell
      function in the gut. However, the underlying mechanisms remain unclear. Here we
      demonstrate that IL-17A signaling in colonic epithelial cells (CECs) increases
      TNF-alpha-induced PI3K-AKT and ERK phosphorylation and inhibits TNF-alpha induced
      expression of IL-12P35 and of a Th1 cell chemokine, CXCL11 at mRNA level. In a co
      culture system using HT-29 cells and PBMCs, IL-17A inhibited TNF-alpha-induced IL
      12P35 expression by HT-29 cells and led to decreased expression of IFN-gamma and
      T-bet by PBMCs. Finally, adoptive transfer of CECs from mice with Crohn's Disease
      (CD) led to an enhanced Th1 cell response and exacerbated colitis in CD mouse
      recipients. The pathogenic effect of CECs derived from CD mice was reversed by co
      administration of recombinant IL-17A. Our data demonstrate a new IL-17A-mediated
      regulatory mechanism in CD. A better understanding of this pathway might shed new
      light on the pathogenesis of CD.

PMID- 24586982
TI  - Efficacy evaluation of fungus Syncephalastrum racemosum and nematicide avermectin
      against the root-knot nematode Meloidogyne incognita on cucumber.
AB  - The root-knot nematode (RKN) is one of the most damaging agricultural
      pests.Effective biological control is need for controlling this destructive
      pathogen in organic farming system. During October 2010 to 2011, the nematicidal
      effects of the Syncephalastrum racemosum fungus and the nematicide, avermectin,
      alone or combined were tested against the RKN (Meloidogyne incognita) on cucumber
      under pot and field condition in China. Under pot conditions, the application of
      S. racemosum alone or combined with avermectin significantly increased the plant
      vigor index by 31.4% and 10.9%, respectively compared to the M. incognita
      inoculated control. However, treatment with avermectin alone did not
      significantly affect the plant vigor index. All treatments reduced the number of
      root galls and juvenile nematodes compared to the untreated control. Under
      greenhouse conditions, all treatments reduced the disease severity and enhanced
      fruit yield compared to the untreated control. Fewer nematodes infecting plant
      roots were observed after treatment with avermectin alone, S. racemosum alone or
      their combination compared to the M. incognita-inoculated control. Among all the
      treatments, application of avermectin or S. racemosum combined with avermectin
      was more effective than the S. racemosum treatment. Our results showed that
      application of S. racemosum combined with avermectin not only reduced the
      nematode number and plant disease severity but also enhanced plant vigor and
      yield. The results indicated that the combination of S. racemosum with avermectin
      could be an effective biological component in integrated management of RKN on
      cucumber. 

PMID- 24586983
TI  - Identification of vital and dispensable sulfur utilization factors in the
      Plasmodium apicoplast.
AB  - Iron-sulfur [Fe-S] clusters are ubiquitous and critical cofactors in diverse
      biochemical processes. They are assembled by distinct [Fe-S] cluster biosynthesis
      pathways, typically in organelles of endosymbiotic origin. Apicomplexan
      parasites, including Plasmodium, the causative agent of malaria, harbor two
      separate [Fe-S] cluster biosynthesis pathways in the their mitochondrion and
      apicoplast. In this study, we systematically targeted the five nuclear-encoded
      sulfur utilization factors (SUF) of the apicoplast [Fe-S] cluster biosynthesis
      pathway by experimental genetics in the murine malaria model parasite Plasmodium
      berghei. We show that four SUFs, namely SUFC, D, E, and S are refractory to
      targeted gene deletion, validating them as potential targets for antimalarial
      drug development. We achieved targeted deletion of SUFA, which encodes a
      potential [Fe-S] transfer protein, indicative of a dispensable role during
      asexual blood stage growth in vivo. Furthermore, no abnormalities were observed
      during Plasmodium life cycle progression in the insect and mammalian hosts.
      Fusion of a fluorescent tag to the endogenous P. berghei SUFs demonstrated that
      all loci were accessible to genetic modification and that all five tagged SUFs
      localize to the apicoplast. Together, our experimental genetics analysis
      identifies the key components of the SUF [Fe-S] cluster biosynthesis pathway in
      the apicoplast of a malarial parasite and shows that absence of SUFC, D, E, or S
      is incompatible with Plasmodium blood infection in vivo. 

PMID- 24586984
TI  - Serum peroxiredoxin 4: a marker of oxidative stress associated with mortality in
      type 2 diabetes (ZODIAC-28).
AB  - BACKGROUND: Oxidative stress plays an underlying pathophysiologic role in the
      development of diabetes complications. The aim of this study was to investigate
      peroxiredoxin 4 (Prx4), a proposed novel biomarker of oxidative stress, and its
      association with and capability as a biomarker in predicting (cardiovascular)
      mortality in type 2 diabetes mellitus. METHODS: Prx4 was assessed in baseline
      serum samples of 1161 type 2 diabetes patients. Cox proportional hazard models
      were used to evaluate the relationship between Prx4 and (cardiovascular)
      mortality. Risk prediction capabilities of Prx4 for (cardiovascular) mortality
      were assessed with Harrell's C statistic, the integrated discrimination
      improvement and net reclassification improvement. RESULTS: Mean age was 67 and
      the median diabetes duration was 4.0 years. After a median follow-up period of
      5.8 years, 327 patients died; 137 cardiovascular deaths. Prx4 was associated with
      (cardiovascular) mortality. The Cox proportional hazard models added the
      variables: Prx4 (model 1); age and gender (model 2), and BMI, creatinine,
      smoking, diabetes duration, systolic blood pressure, cholesterol-HDL ratio,
      history of macrovascular complications, and albuminuria (model 3). Hazard ratios
      (HR) (95% CI) for cardiovascular mortality were 1.93 (1.57 - 2.38), 1.75 (1.39 -
      2.20), and 1.63 (1.28 - 2.09) for models 1, 2 and 3, respectively. HR for all
      cause mortality were 1.73 (1.50 - 1.99), 1.50 (1.29 - 1.75), and 1.44 (1.23 -
      1.67) for models 1, 2 and 3, respectively. Addition of Prx4 to the traditional
      risk factors slightly improved risk prediction of (cardiovascular) mortality.
      CONCLUSIONS: Prx4 is independently associated with (cardiovascular) mortality in
      type 2 diabetes patients. After addition of Prx4 to the traditional risk factors,
      there was a slightly improvement in risk prediction of (cardiovascular) mortality
      in this patient group.

PMID- 24586985
TI  - Understanding the distribution of marine megafauna in the English channel region:
      identifying key habitats for conservation within the busiest seaway on earth.
AB  - The temperate waters of the North-Eastern Atlantic have a long history of
      maritime resource richness and, as a result, the European Union is endeavouring
      to maintain regional productivity and biodiversity. At the intersection of these
      aims lies potential conflict, signalling the need for integrated, cross-border
      management approaches. This paper focuses on the marine megafauna of the region.
      This guild of consumers was formerly abundant, but is now depleted and protected
      under various national and international legislative structures. We present a
      meta-analysis of available megafauna datasets using presence-only distribution
      models to characterise suitable habitat and identify spatially-important regions
      within the English Channel and southern bight of the North Sea. The integration
      of studies from dedicated and opportunistic observer programmes in the United
      Kingdom and France provide a valuable perspective on the spatial and seasonal
      distribution of various taxonomic groups, including large pelagic fishes and
      sharks, marine mammals, seabirds and marine turtles. The Western English Channel
      emerged as a hotspot of biodiversity for megafauna, while species richness was
      low in the Eastern English Channel. Spatial conservation planning is complicated
      by the highly mobile nature of marine megafauna, however they are important
      components of the marine environment and understanding their distribution is a
      first crucial step toward their inclusion into marine ecosystem management. 

PMID- 24586986
TI  - Association between vitamin D status and risk of metabolic syndrome among Korean
      postmenopausal women.
AB  - This study aimed to investigate the association between serum levels of 25
      hydroxyvitamin D [25(OH)D] and metabolic syndrome along with its associated risk
      factors in Korean postmenopausal women. This study was performed using data from
      the KNHANES 2008-2010 study and included 4,364 postmenopausal Korean women.
      Clinical and other objective characteristics, seasonality, and presence of
      metabolic syndrome with its five components were evaluated and correlated with
      the serum levels of 25(OH)D. Although no statistically significant associations
      were observed between the levels of serum 25(OH)D and the prevalence of metabolic
      syndrome, the adjusted OR for elevated blood pressure, elevated triglycerides
      (TGs), and reduced high-density lipoprotein cholesterol (HDL-C) showed tendency
      to decrease sequentially as tertiles of serum 25(OH)D levels increased (p for
      trends  = 0.066, 0.043, and 0.010, respectively). Women in the highest tertile of
      serum 25(OH)D showed a significant decrease in the prevalence of elevated blood
      pressure, elevated TGs, and reduced HDL-C as compared with those in the lowest
      tertile of serum 25(OH)D (p = 0.020, 0.014, and 0.002, respectively). Based on
      these results, we consider that adequate serum levels of 25(OH)D in Korean
      postmenopausal women may not entirely indicate a lower risk of developing
      metabolic syndrome. However, adequate serum levels of 25(OH)D are significantly
      associated with a decrease in elevated blood pressure, elevated TGs, and reduced
      HDL-C levels in postmenopausal women.

PMID- 24586987
TI  - Prevalence and predictors of HIV among Chinese tuberculosis patients by provider
      initiated HIV testing and counselling (PITC): a multisite study in South Central
      of China.
AB  - BACKGROUND: Tuberculosis (TB) and HIV are two worldwide public health concerns.
      Co-infection of these two diseases has been considered to be a major obstacle for
      the global efforts in reaching the goals for the prevention of HIV and TB.
      METHOD: A comprehensive cross-sectional study was conducted to recruit TB
      patients in three provinces (Guangxi, Henan and Sichuan) of China between April 1
      and September 30, 2010. RESULTS: A total of 1,032 consenting TB patients attended
      this survey during the study period. Among the participants, 3.30% were HIV
      positive; about one quarter had opportunistic infections. Nearly half of the
      participants were 50 years or older, the majority were male and about one third
      were from minority ethnic groups. After adjusting for site, gender and areas of
      residence (using the partial/selective Model 1), former commercial plasma donors
      (adjusted OR [aOR] = 33.71) and injecting drug users(aOR = 15.86) were found to
      have significantly higher risk of being HIV-positivity. In addition, having
      extramarital sexual relationship (aOR = 307.16), being engaged in commercial sex
      (aOR = 252.37), suffering from opportunistic infections in the past six months
      (aOR = 2.79), losing 10% or more of the body weight in the past six months (aOR =
      5.90) and having abnormal chest X-ray findings (aOR = 20.40) were all
      significantly associated with HIV seropositivity (each p<0.05). CONCLUSIONS: HIV
      prevalence among TB patients was high in the study areas of China. To control the
      dual epidemic, intervention strategies targeting socio-demographic and behavioral
      factors associated with higher risk of TB-HIV co-infection are urgently called
      for.

PMID- 24586988
TI  - A phenological timetable of oak growth under experimental drought and air
      warming.
AB  - Climate change is expected to increase temperature and decrease summer
      precipitation in Central Europe. Little is known about how warming and drought
      will affect phenological patterns of oaks, which are considered to possess
      excellent adaptability to these climatic changes. Here, we investigated bud burst
      and intra-annual shoot growth of Quercus robur, Q. petraea and Q. pubescens grown
      on two different forest soils and exposed to air warming and drought.
      Phenological development was assessed over the course of three growing seasons.
      Warming advanced bud burst by 1-3 days  degrees C-1 and led to an earlier start
      of intra-annual shoot growth. Despite this phenological shift, total time span of
      annual growth and shoot biomass were not affected. Drought changed the frequency
      and intensity of intra-annual shoot growth and advanced bud burst in the
      subsequent spring of a severe summer drought by 1-2 days. After re-wetting, shoot
      growth recovered within a few days, demonstrating the superior drought tolerance
      of this tree genus. Our findings show that phenological patterns of oaks are
      modified by warming and drought but also suggest that ontogenetic factors and/or
      limitations of water and nutrients counteract warming effects on the biomass and
      the entire span of annual shoot growth.

PMID- 24586989
TI  - Development of a hierarchical variable-number tandem repeat typing scheme for
      Mycobacterium tuberculosis in China.
AB  - Molecular typing based on variable-number tandem repeats (VNTR) analysis is a
      promising tool for identifying transmission of Mycobacterium tuberculosis.
      However, the currently proposed 15- and 24-locus VNTR sets (VNTR-15/24) only have
      limited resolution and contain too many loci for large-scale typing in high
      burden countries. To develop an optimal typing scheme in China, we evaluated the
      resolution and robustness of 25 VNTR loci, using population-based collections of
      1362 clinical isolates from six provinces across the country. The resolution of
      most loci showed considerable variations among regions. By calculating the
      average resolution of all possible combinations of 20 robust loci, we identified
      an optimal locus set with a minimum of 9 loci (VNTR-9) that could achieve
      comparable resolution of the standard VNTR-15. The VNTR-9 had consistently high
      resolutions in all six regions, and it was highly concordant with VNTR-15 for
      defining both clustered and unique genotypes. Furthermore, VNTR-9 was
      phylogenetically informative for classifying lineages/sublineages of M.
      tuberculosis. Three hypervariable loci (HV-3), VNTR 3232, VNTR 3820 and VNTR
      4120, were proved important for further differentiating unrelated clustered
      strains based on VNTR-9. We propose the optimized VNTR-9 as first-line method and
      the HV-3 as second-line method for molecular typing of M. tuberculosis in China
      and surrounding countries. The development of hierarchical VNTR typing methods
      that can achieve high resolution with a small number of loci could be suitable
      for molecular epidemiology study in other high burden countries. 

PMID- 24586990
TI  - Dehydroepiandrosterone sulfate (DHEAS) stimulates the first step in the
      biosynthesis of steroid hormones.
AB  - Dehydroepiandrosterone sulfate (DHEAS) is the most abundant circulating steroid
      in human, with the highest concentrations between age 20 and 30, but displaying a
      significant decrease with age. Many beneficial functions are ascribed to DHEAS.
      Nevertheless, long-term studies are very scarce concerning the intake of DHEAS
      over several years, and molecular investigations on DHEAS action are missing so
      far. In this study, the role of DHEAS on the first and rate-limiting step of
      steroid hormone biosynthesis was analyzed in a reconstituted in vitro system,
      consisting of purified CYP11A1, adrenodoxin and adrenodoxin reductase. DHEAS
      enhances the conversion of cholesterol by 26%. Detailed analyses of the mechanism
      of DHEAS action revealed increased binding affinity of cholesterol to CYP11A1 and
      enforced interaction with the electron transfer partner, adrenodoxin. Difference
      spectroscopy showed K(d)-values of 40 +/- 2.7 uM and 24.8 +/- 0.5 uM for CYP11A1
      and cholesterol without and with addition of DHEAS, respectively. To determine
      the K(d)-value for CYP11A1 and adrenodoxin, surface plasmon resonance
      measurements were performed, demonstrating a K(d)-value of 3.0 +/- 0.35 nM (with
      cholesterol) and of 2.4 +/- 0.05 nM when cholesterol and DHEAS were added.
      Kinetic experiments showed a lower Km and a higher kcat value for CYP11A1 in the
      presence of DHEAS leading to an increase of the catalytic efficiency by 75%.
      These findings indicate that DHEAS affects steroid hormone biosynthesis on a
      molecular level resulting in an increased formation of pregnenolone.

PMID- 24586991
TI  - Targeted metabolomics identifies reliable and stable metabolites in human serum
      and plasma samples.
AB  - BACKGROUND: Information regarding the variability of metabolite levels over time
      in an individual is required to estimate the reproducibility of metabolite
      measurements. In intervention studies, it is critical to appropriately judge
      changes that are elicited by any kind of intervention. The pre-analytic phase
      (collection, transport and sample processing) is a particularly important
      component of data quality in multi-center studies. METHODS: Reliability of
      metabolites (within-and between-person variance, intraclass correlation
      coefficient) and stability (shipment simulation at different temperatures, use of
      gel-barrier collection tubes, freeze-thaw cycles) were analyzed in fasting serum
      and plasma samples of 22 healthy human subjects using a targeted LC-MS approach.
      RESULTS: Reliability of metabolite measurements was higher in serum compared to
      plasma samples and was good in most saturated short-and medium-chain
      acylcarnitines, amino acids, biogenic amines, glycerophospholipids, sphingolipids
      and hexose. The majority of metabolites were stable for 24 h on cool packs and at
      room temperature in non-centrifuged tubes. Plasma and serum metabolite stability
      showed good coherence. Serum metabolite concentrations were mostly unaffected by
      tube type and one or two freeze-thaw cycles. CONCLUSION: A single time point
      measurement is assumed to be sufficient for a targeted metabolomics analysis of
      most metabolites. For shipment, samples should ideally be separated and frozen
      immediately after collection, as some amino acids and biogenic amines become
      unstable within 3 h on cool packs. Serum gel-barrier tubes can be used safely for
      this process as they have no effect on concentration in most metabolites.
      Shipment of non-centrifuged samples on cool packs is a cost-efficient alternative
      for most metabolites.

PMID- 24586992
TI  - Inter-individual differences in the initial 80 minutes of motor learning of
      handrim wheelchair propulsion.
AB  - Handrim wheelchair propulsion is a cyclic skill that needs to be learned during
      rehabilitation. Yet it is unclear how inter-individual differences in motor
      learning impact wheelchair propulsion practice. Therefore we studied how early
      identified motor learning styles in novice able-bodied participants impact the
      outcome of a low-intensity wheelchair-practice intervention. Over a 12-minute pre
      test, 39 participants were split in two groups based on a relative 10% increase
      in mechanical efficiency. Following the pretest the participants continued one of
      four different low-intensity wheelchair practice interventions, yet all performed
      in the same trial-setup with a total 80-minute dose at 1.11 m/s at 0.20 W/kg.
      Instead of focusing on the effect of the different interventions, we focused on
      differences in motor learning between participants over the intervention. Twenty
      six participants started the pretest with a lower mechanical efficiency and a
      less optimal propulsion technique, but showed a fast improvement during the first
      12 minutes and this effect continued over the 80 minutes of practice. Eventually
      these initially fast improvers benefitted more from the given practice indicated
      by a better propulsion technique (like reduced frequency and increased stroke
      angle) and a higher mechanical efficiency. The initially fast improvers also had
      a higher intra-individual variability in the pre and posttest, which possibly
      relates to the increased motor learning of the initially fast improvers. Further
      exploration of the common characteristics of different types of learners will
      help to better tailor rehabilitation to the needs of wheelchair-dependent persons
      and improve our understanding of cyclic motor learning processes. 

PMID- 24586993
TI  - IgE-associated IGHV genes from venom and peanut allergic individuals lack
      mutational evidence of antigen selection.
AB  - Antigen selection of B cells within the germinal center reaction generally leads
      to the accumulation of replacement mutations in the complementarity-determining
      regions (CDRs) of immunoglobulin genes. Studies of mutations in IgE-associated
      VDJ gene sequences have cast doubt on the role of antigen selection in the
      evolution of the human IgE response, and it may be that selection for high
      affinity antibodies is a feature of some but not all allergic diseases. The
      severity of IgE-mediated anaphylaxis is such that it could result from higher
      affinity IgE antibodies. We therefore investigated IGHV mutations in IgE
      associated sequences derived from ten individuals with a history of anaphylactic
      reactions to bee or wasp venom or peanut allergens. IgG sequences, which more
      certainly experience antigen selection, served as a control dataset. A total of
      6025 unique IgE and 5396 unique IgG sequences were generated using high
      throughput 454 pyrosequencing. The proportion of replacement mutations seen in
      the CDRs of the IgG dataset was significantly higher than that of the IgE
      dataset, and the IgE sequences showed little evidence of antigen selection. To
      exclude the possibility that 454 errors had compromised analysis, rigorous
      filtering of the datasets led to datasets of 90 core IgE sequences and 411 IgG
      sequences. These sequences were present as both forward and reverse reads, and so
      were most unlikely to include sequencing errors. The filtered datasets confirmed
      that antigen selection plays a greater role in the evolution of IgG sequences
      than of IgE sequences derived from the study participants. 

PMID- 24586994
TI  - The effect of rosuvastatin on inflammation, matrix turnover and left ventricular
      remodeling in dilated cardiomyopathy: a randomized, controlled trial.
AB  - BACKGROUND: Dilated cardiomyopathy is characterized by left ventricular
      dilatation and dysfunction. Inflammation and adverse remodeling of the
      extracellular matrix may be involved in the pathogenesis. Statins reduce levels
      of low density lipoprotein cholesterol, but may also attenuate inflammation and
      affect matrix remodeling. We hypothesized that treatment with rosuvastatin would
      reduce or even reverse left ventricular remodeling in dilated cardiomyopathy.
      MATERIALS AND METHODS: In this multicenter, randomized, double blind, placebo
      controlled study, 71 patients were randomized to 10 mg of rosuvastatin or
      matching placebo. Physical examination, blood sampling, echocardiography and
      cardiac magnetic resonance imaging were performed at baseline and at six months'
      follow-up. The pre-specified primary end point was the change in left ventricular
      ejection fraction from baseline to six months. RESULTS: Over all, left
      ventricular ejection fraction improved 5 percentage points over the duration of
      the study, but there was no difference in the change in left ventricular ejection
      fraction between patients allocated to rosuvastatin and those allocated to
      placebo. Whereas serum low density lipoprotein cholesterol concentration fell
      significantly in the treatment arm, rosuvastatin did not affect plasma or serum
      levels of a wide range of inflammatory variables, including C-reactive protein.
      The effect on markers of extracellular matrix remodeling was modest. CONCLUSION:
      Treatment with rosuvastatin does not improve left ventricular ejection fraction
      in patients with dilated cardiomyopathy. TRIAL REGISTRATION: ClinicalTrials.gov
      NCT00505154.

PMID- 24586995
TI  - A tale of two reductases: extending the bacteriochlorophyll biosynthetic pathway
      in E. coli.
AB  - The creation of a synthetic microbe that can harvest energy from sunlight to
      drive its metabolic processes is an attractive approach to the economically
      viable biosynthetic production of target compounds. Our aim is to design and
      engineer a genetically tractable non-photosynthetic microbe to produce light
      harvesting molecules. Previously we created a modular, multienzyme system for the
      heterologous production of intermediates of the bacteriochlorophyll (BChl)
      pathway in E. coli. In this report we extend this pathway to include a substrate
      promiscuous 8-vinyl reductase that can accept multiple intermediates of BChl
      biosynthesis. We present an informative comparative analysis of homologues of 8
      vinyl reductase from the model photosynthetic organisms Rhodobacter sphaeroides
      and Chlorobaculum tepidum. The first purification of the enzymes leads to their
      detailed biochemical and biophysical characterization. The data obtained reveal
      that the two 8-vinyl reductases are substrate promiscuous, capable of reducing
      the C8-vinyl group of Mg protoporphyrin IX, Mg protoporphyrin IX methylester, and
      divinyl protochlorophyllide. However, activity is dependent upon the presence of
      chelated Mg(2+) in the porphyrin ring, with no activity against non-Mg(2+)
      chelated intermediates observed. Additionally, CD analyses reveal that the two 8
      vinyl reductases appear to bind the same substrate in a different fashion.
      Furthermore, we discover that the different rates of reaction of the two 8-vinyl
      reductases both in vitro, and in vivo as part of our engineered system, results
      in the suitability of only one of the homologues for our BChl pathway in E. coli.
      Our results offer the first insights into the different functionalities of
      homologous 8-vinyl reductases. This study also takes us one step closer to the
      creation of a nonphotosynthetic microbe that is capable of harvesting energy from
      sunlight for the biosynthesis of molecules of choice. 

PMID- 24586996
TI  - Toll-like receptor agonist augments virus-like particle-mediated protection from
      Ebola virus with transient immune activation.
AB  - Identifying safe and effective adjuvants is critical for the advanced development
      of protein-based vaccines. Pattern recognition receptor (PRR) agonists are
      increasingly being explored as potential adjuvants, but there is concern that the
      efficacy of these molecules may be dependent on potentially dangerous levels of
      non-specific immune activation. The filovirus virus-like particle (VLP) vaccine
      protects mice, guinea pigs, and nonhuman primates from viral challenge. In this
      study, we explored the impact of a stabilized dsRNA mimic, polyICLC, on VLP
      vaccination of C57BL/6 mice and Hartley guinea pigs. We show that at dose levels
      as low as 100 ng, the adjuvant increased the efficacy of the vaccine in mice.
      Antigen-specific, polyfunctional CD4 and CD8 T cell responses and antibody
      responses increased significantly upon inclusion of adjuvant. To determine
      whether the efficacy of polyICLC correlated with systemic immune activation, we
      examined serum cytokine levels and cellular activation in the draining lymph
      node. PolyICLC administration was associated with increases in TNFalpha, IL6,
      MCP1, MIP1alpha, KC, and MIP1beta levels in the periphery and with the activation
      of dendritic cells (DCs), NK cells, and B cells. However, this activation
      resolved within 24 to 72 hours at efficacious adjuvant dose levels. These studies
      are the first to examine the polyICLC-induced enhancement of antigen-specific
      immune responses in the context of non-specific immune activation, and they
      provide a framework from which to consider adjuvant dose levels. 

PMID- 24586997
TI  - Meta-analysis of the rs4779584 polymorphism and colorectal cancer risk.
AB  - PURPOSE: Several researchers have suggested that the rs4779584 (15q13.3)
      polymorphism is associated with an increased risk of developing colorectal cancer
      (CRC). However, past results remain inconclusive. We addressed this controversy
      by performing a meta-analysis of the relationship between rs4779584 of GREM1-SCG5
      and colorectal cancer. METHODS: We selected 12 case-control studies involving
      11,769 cases of CRC and 14,328 healthy controls. The association between the
      rs4779584 polymorphism and CRC was examined by the overall odds ratio (OR) with a
      95% confidence interval (CI). We used different genetic model analyses,
      sensitivity analyses, and assessments of bias in our meta-analysis. RESULTS:
      GREM1-SCG5 rs4779584 polymorphisms were associated with CRC in all of the genetic
      models that were examined in this meta-analysis of 12 case-control studies.
      CONCLUSION: GREM1-SCG5 rs4779584 polymorphisms may increase the risk of
      developing colorectal cancer.

PMID- 24586998
TI  - Ecology and caudal skeletal morphology in birds: the convergent evolution of
      pygostyle shape in underwater foraging taxa.
AB  - Birds exhibit a specialized tail that serves as an integral part of the flight
      apparatus, supplementing the role of the wings in facilitating high performance
      aerial locomotion. The evolution of this function for the tail contributed to the
      diversification of birds by allowing them to utilize a wider range of flight
      behaviors and thus exploit a greater range of ecological niches. The shape of the
      wings and the tail feathers influence the aerodynamic properties of a bird.
      Accordingly, taxa that habitually utilize different flight behaviors are
      characterized by different flight apparatus morphologies. This study explores
      whether differences in flight behavior are also associated with variation in
      caudal vertebra and pygostyle morphology. Details of the tail skeleton were
      characterized in 51 Aequornithes and Charadriiformes species. Free caudal
      vertebral morphology was measured using linear metrics. Variation in pygostyle
      morphology was characterized using Elliptical Fourier Analysis, a geometric
      morphometric method for the analysis of outline shapes. Each taxon was
      categorized based on flight style (flap, flap-glide, dynamic soar, etc.) and
      foraging style (aerial, terrestrial, plunge dive, etc.). Phylogenetic MANOVAs and
      Flexible Discriminant Analyses were used to test whether caudal skeletal
      morphology can be used to predict flight behavior. Foraging style groups differ
      significantly in pygostyle shape, and pygostyle shape predicts foraging style
      with less than 4% misclassification error. Four distinct lineages of underwater
      foraging birds exhibit an elongate, straight pygostyle, whereas aerial and
      terrestrial birds are characterized by a short, dorsally deflected pygostyle.
      Convergent evolution of a common pygostyle phenotype in diving birds suggests
      that this morphology is related to the mechanical demands of using the tail as a
      rudder during underwater foraging. Thus, distinct locomotor behaviors influence
      not only feather attributes but also the underlying caudal skeleton, reinforcing
      the importance of the entire caudal locomotor module in avian ecological
      diversification. 

PMID- 24586999
TI  - Genome re-sequencing and functional analysis places the Phytophthora sojae
      avirulence genes Avr1c and Avr1a in a tandem repeat at a single locus.
AB  - The aim of this work was to map and identify the Phytophthora sojae Avr1c gene.
      Progeny from a cross of P. sojae strains ACR10*P7076 were tested for virulence on
      plants carrying Rps1c. Results indicate that avirulence segregates as a dominant
      trait. We mapped the Avr1c locus by performing whole genome re-sequencing of
      composite libraries created from pooled samples. Sequence reads from avirulent
      (Pool1) and virulent (Pool2) samples were aligned to the reference genome and
      single nucleotide polymorphisms (SNP) were identified for each pool. High quality
      SNPs were filtered to select for positions where SNP frequency was close to
      expected values for each pool. Only three SNP positions fit all requirements, and
      these occurred in close proximity. Additional DNA markers were developed and
      scored in the F2 progeny, producing a fine genetic map that places Avr1c within
      the Avr1a gene cluster. Transient expression of Avr1c or Avr1a triggers cell
      death on Rps1c plants, but Avr1c does not trigger cell death on Rps1a plants.
      Sequence comparisons show that the RXLR effector genes Avr1c and Avr1a are
      closely related paralogs. Gain of virulence on Rps1c in P. sojae strain P7076 is
      achieved by gene deletion, but in most other strains this is accomplished by gene
      silencing. This work provides practical tools for crop breeding and diagnostics,
      as the Rps1c gene is widely deployed in commercial soybean cultivars.

PMID- 24587000
TI  - Ocepeia (Middle Paleocene of Morocco): the oldest skull of an afrotherian mammal.
AB  - While key early(iest) fossils were recently discovered for several crown
      afrotherian mammal orders, basal afrotherians, e.g., early Cenozoic species that
      comprise sister taxa to Paenungulata, Afroinsectiphilia or Afrotheria, are nearly
      unknown, especially in Africa. Possible stem condylarth-like relatives of the
      Paenungulata (hyraxes, sea-cows, elephants) include only Abdounodus hamdii and
      Ocepeia daouiensis from the Selandian of Ouled Abdoun Basin, Morocco, both
      previously only documented by lower teeth. Here, we describe new fossils of
      Ocepeia, including O.grandis n. sp., and a sub-complete skull of O. daouiensis,
      the first known before the Eocene for African placentals. O.daouiensis skull
      displays a remarkable mosaic of autapomophic, ungulate-like and generalized
      eutherian-like characters. Autapomorphies include striking anthropoid-like
      characters of the rostrum and dentition. Besides having a basically eutherian
      like skull construction, Ocepeia daouiensis is characterized by ungulate-like,
      and especially paenungulate-like characters of skull and dentition (e.g.,
      selenodonty). However, some plesiomorphies such as absence of hypocone exclude
      Ocepeia from crown Paenungulata. Such a combination of plesiomorphic and derived
      characters best fits with a stem position of Ocepeia relative to Paenungulata. In
      our cladistic analyses Ocepeia is included in Afrotheria, but its shared derived
      characters with paenungulates are not optimized as exclusive synapomorphies.
      Rather, within Afrotheria Ocepeia is reconstructed as more closely related to
      insectivore-like afroinsectiphilians (i.e., aardvarks, sengis, tenrecs, and
      golden moles) than to paenungulates. This results from conflict with undetected
      convergences of Paenungulata and Perissodactyla in our cladistic analysis, such
      as the shared bilophodonty. The selenodont pattern best supports the stem
      paenungulate position of Ocepeia; that, however, needs further support. The
      remarkable character mosaic of Ocepeia makes it the first known "transitional
      fossil" between insectivore-like and ungulate-like afrotherians. In addition, the
      autapomorphic family Ocepeiidae supports the old--earliest Tertiary or Cretaceous
      -endemic evolution of placentals in Africa, in contrast to hypotheses rooting
      afrotherians in Paleogene Laurasian "condylarths".

PMID- 24587001
TI  - Clinical study of critical patients with hemorrhagic fever with renal syndrome
      complicated by acute respiratory distress syndrome.
AB  - OBJECTIVES: The aim of this study was to investigate the clinical characteristics
      and outcomes of critical patients with hemorrhagic fever with renal syndrome
      (HFRS) complicated by acute respiratory distress syndrome (ARDS). MATERIALS AND
      METHODS: To observe the demographic, epidemiological and clinical
      characteristics, and to explore the predictive effects for prognosis in
      laboratory findings, we conducted a detailed retrospective analysis of clinical
      records for critical patients with HFRS complicated by ARDS, treated at the
      center for infectious diseases, Tangdu Hospital, between January 2008 and
      December 2012. RESULTS: A total of 48 critical patients with laboratory confirmed
      HFRS accompanied by ARDS were enrolled in the study, including 27 survivors and
      21 non-survivors, with a fatality rate of 43.75%. Thirty-one individuals (64.6%)
      contracted HFRS between the months of September and December. The non-survivors
      tended to have lower incidence of overlapping phase (P = 0.025). There were no
      obvious differences in the needs for mechanical ventilation (MV) and renal
      replacement therapy (RRT), except for the need for vasoactive drugs between the
      survivors and non-survivors (P = 0.001). The non-survivors were found to have
      higher frequencies of encephalopathy, refractory shock and multiple organ
      dysfunction syndrome (MODS), lower incidences of acute renal failure (ARF) and
      secondary hypertension (P<0.05). The non-survivors tended to have lower levels of
      serum creatinine (Scr) (P<0.001) and fibrinogen (Fib) (P = 0.003), higher
      incidences of prolonged prothrombin time (PT) (P = 0.006) and activated partial
      thromboplastin time (APTT) (P = 0.020) and higher levels of aspartate
      aminotransferase (AST) (P = 0.015), and the laboratory parameters mentioned above
      reached statistical significance for predicting prognosis (P<0.05). CONCLUSION:
      The high mortality rate of critical patients with HFRS complicated by ARDS
      emphasizes the importance of clinicians' alertness and timely initiation of
      systemic supportive therapy.

PMID- 24587002
TI  - Neurodegenerative disorder risk in idiopathic REM sleep behavior disorder: study
      in 174 patients.
AB  - OBJECTIVE: To estimate the risk for developing a defined neurodegenerative
      syndrome in a large cohort of idiopathic REM sleep behavior disorder (IRBD)
      patients with long follow-up. METHODS: Using the Kaplan-Meier method, we
      estimated the disease-free survival rate from defined neurodegenerative syndromes
      in all the consecutive IRBD patients diagnosed and followed-up in our tertiary
      referal sleep center between November 1991 and July 2013. RESULTS: The cohort
      comprises 174 patients with a median age at diagnosis of IRBD of 69 years and a
      median follow-up of four years. The risk of a defined neurodegenerative syndrome
      from the time of IRBD diagnosis was 33.1% at five years, 75.7% at ten years, and
      90.9% at 14 years. The median conversion time was 7.5 years. Emerging diagnoses
      (37.4%) were dementia with Lewy bodies (DLB) in 29 subjects, Parkinson disease
      (PD) in 22, multiple system atrophy (MSA) in two, and mild cognitive impairment
      (MCI) in 12. In six cases, in whom postmortem was performed, neuropathological
      examination disclosed neuronal loss and widespread Lewy-type pathology in the
      brain in each case. CONCLUSIONS: In a large IRBD cohort diagnosed in a tertiary
      referal sleep center, prolonged follow-up indicated that the majority of patients
      are eventually diagnosed with the synucleinopathies PD, DLB and less frequently
      MSA. IRBD represented the prodromal period of these conditions. Our findings in
      IRBD have important implications in clinical practice, in the investigation of
      the early pathological events occurring in the synucleinopathies, and for the
      design of interventions with potential disease-modifying agents.

PMID- 24587003
TI  - Lipoxin A4 prevents the progression of de novo and established endometriosis in a
      mouse model by attenuating prostaglandin E2 production and estrogen signaling.
AB  - Endometriosis, a leading cause of pelvic pain and infertility, is characterized
      by ectopic growth of endometrial-like tissue and affects approximately 176
      million women worldwide. The pathophysiology involves inflammatory and angiogenic
      mediators as well as estrogen-mediated signaling and novel, improved therapeutics
      targeting these pathways are necessary. The aim of this study was to investigate
      mechanisms leading to the establishment and progression of endometriosis as well
      as the effect of local treatment with Lipoxin A4 (LXA4), an anti-inflammatory and
      pro-resolving lipid mediator that we have recently characterized as an estrogen
      receptor agonist. LXA4 treatment significantly reduced endometriotic lesion size
      and downregulated the pro-inflammatory cytokines IL-1beta and IL-6, as well as
      the angiogenic factor VEGF. LXA4 also inhibited COX-2 expression in both
      endometriotic lesions and peritoneal fluid cells, resulting in attenuated
      peritoneal fluid Prostaglandin E2 (PGE2) levels. Besides its anti-inflammatory
      effects, LXA4 differentially regulated the expression and activity of the matrix
      remodeling enzyme matrix metalloproteinase (MMP)-9 as well as modulating
      transforming growth factor (TGF)-beta isoform expression within endometriotic
      lesions and in peritoneal fluid cells. We also report for first time that LXA4
      attenuated aromatase expression, estrogen signaling and estrogen-regulated genes
      implicated in cellular proliferation in a mouse model of disease. These effects
      were observed both when LXA4 was administered prior to disease induction and
      during established disease. Collectively, our findings highlight potential
      targets for the treatment of endometriosis and suggest a pleotropic effect of
      LXA4 on disease progression, by attenuating pro-inflammatory and angiogenic
      mediators, matrix remodeling enzymes, estrogen metabolism and signaling, as well
      as downstream proliferative pathways.

PMID- 24587004
TI  - Microvesicle shedding and lysosomal repair fulfill divergent cellular needs
      during the repair of streptolysin O-induced plasmalemmal damage.
AB  - Pathogenic bacteria secrete pore-forming toxins that permeabilize the plasma
      membrane of host cells. Nucleated cells possess protective mechanisms that repair
      toxin-damaged plasmalemma. Currently two putative repair scenarios are debated:
      either the isolation of the damaged membrane regions and their subsequent
      expulsion as microvesicles (shedding) or lysosome-dependent repair might allow
      the cell to rid itself of its toxic cargo and prevent lysis. Here we provide
      evidence that both mechanisms operate in tandem but fulfill diverse cellular
      needs. The prevalence of the repair strategy varies between cell types and is
      guided by the severity and the localization of the initial toxin-induced damage,
      by the morphology of a cell and, most important, by the incidence of the
      secondary mechanical damage. The surgically precise action of microvesicle
      shedding is best suited for the instant elimination of individual toxin pores,
      whereas lysosomal repair is indispensable for mending of self-inflicted
      mechanical injuries following initial plasmalemmal permeabilization by bacterial
      toxins. Our study provides new insights into the functioning of non-immune
      cellular defenses against bacterial pathogens. 

PMID- 24587005
TI  - Nitric oxide dysregulation in platelets from patients with advanced Huntington
      disease.
AB  - Nitric oxide (NO) is a biologically active inorganic molecule involved in the
      regulation of many physiological processes, such as control of blood flow,
      platelet adhesion, endocrine function, neurotransmission and neuromodulation. In
      the present study, for the first time, we investigated the modulation of NO
      signaling in platelets of HD patients. We recruited 55 patients with manifest HD
      and 28 gender- and age-matched healthy controls. Our data demonstrated that NO
      mediated vasorelaxation, when evoked by supernatant from insulin-stimulated HD
      platelets, gradually worsens along disease course. The defective vasorelaxation
      seems to stem from a faulty release of NO from platelets of HD patients and, it
      is associated with impairment of eNOS phosphorylation (Ser(1177)) and activity.
      This study provides important insights about NO metabolism in HD and raises the
      hypothesis that the decrease of NO in platelets of HD individuals could be a good
      tool for monitoring advanced stages of the disease. 

PMID- 24587006
TI  - Randomized pharmacokinetic study comparing subcutaneous and intravenous
      palonosetron in cancer patients treated with platinum based chemotherapy.
AB  - BACKGROUND: Palonosetron is a potent second generation 5- hydroxytryptamine-3
      selective antagonist which can be administered by either intravenous (IV) or oral
      routes, but subcutaneous (SC) administration of palonosetron has never been
      studied, even though it could have useful clinical applications. In this study,
      we evaluate the bioavailability of SC palonosetron. PATIENTS AND METHODS:
      Patients treated with platinum-based chemotherapy were randomized to receive SC
      or IV palonosetron, followed by the alternative route in a crossover manner,
      during the first two cycles of chemotherapy. Blood samples were collected at
      baseline and 10, 15, 30, 45, 60, 90 minutes and 2, 3, 4, 6, 8, 12 and 24 h after
      palonosetron administration. Urine was collected during 12 hours following
      palonosetron. We compared pharmacokinetic parameters including AUC0-24h, t1/2,
      and Cmax observed with each route of administration by analysis of variance
      (ANOVA). RESULTS: From October 2009 to July 2010, 25 evaluable patients were
      included. AUC0-24h for IV and SC palonosetron were respectively 14.1 and 12.7 ng
      * h/ml (p=0.160). Bioavalability of SC palonosetron was 118% (95% IC: 69-168).
      Cmax was lower with SC than with IV route and was reached 15 minutes following SC
      administration. CONCLUSIONS: Palonosetron bioavailability was similar when
      administered by either SC or IV route. This new route of administration might be
      specially useful for outpatient management of emesis and for administration of
      oral chemotherapy. TRIAL REGISTRATION: ClinicalTrials.gov NCT01046240.

PMID- 24587007
TI  - Sutherlandia frutescens ethanol extracts inhibit oxidative stress and
      inflammatory responses in neurons and microglial cells.
AB  - Sutherlandia frutescens (L.) R.Br. (SF) is a medicinal plant indigenous to
      southern Africa and used in folk and contemporary remedies for stress, chronic
      diseases, cancer, and HIV/AIDS. While previous studies have focused on
      physiological effects of SF on cellular and systemic abnormalities associated
      with these diseases, little is known about its effects in the brain and immune
      cells in the central nervous system. Results of this study indicate that ethanol
      extracts of SF (SF-E) suppress NMDA-induced reactive oxygen species (ROS)
      production in neurons, and LPS- and IFNgamma-induced ROS and nitric oxide (NO)
      production in microglial cells. SF-E's action on microglial cells appears to be
      mediated through inhibition of the IFNgamma-induced p-ERK1/2 signaling pathway
      which is central to regulating a number of intracellular metabolic processes
      including enhancing STAT1alpha phosphorylation and filopodia formation. The
      involvement of SF in these pathways suggests the potential for novel therapeutics
      for stress and prevention, and/or treatment of HIV/AIDS as well as other
      inflammatory diseases in the brain. 

PMID- 24587008
TI  - Absence of cardiovascular manifestations in a haploinsufficient Tgfbr1 mouse
      model.
AB  - Loeys-Dietz syndrome (LDS) is an autosomal dominant arterial aneurysm disease
      belonging to the spectrum of transforming growth factor beta (TGFbeta)-associated
      vasculopathies. In its most typical form it is characterized by the presence of
      hypertelorism, bifid uvula/cleft palate and aortic aneurysm and/or arterial
      tortuosity. LDS is caused by heterozygous loss of function mutations in the genes
      encoding TGFbeta receptor 1 and 2 (TGFBR1 and -2), which lead to a paradoxical
      increase in TGFbeta signaling. To address this apparent paradox and to gain more
      insight into the pathophysiology of aneurysmal disease, we characterized a new
      Tgfbr1 mouse model carrying a p.Y378* nonsense mutation. Study of the natural
      history in this model showed that homozygous mutant mice die during embryonic
      development due to defective vascularization. Heterozygous mutant mice aged 6 and
      12 months were morphologically and (immuno)histochemically indistinguishable from
      wild-type mice. We show that the mutant allele is degraded by nonsense mediated
      mRNA decay, expected to result in haploinsufficiency of the mutant allele. Since
      this haploinsufficiency model does not result in cardiovascular malformations, it
      does not allow further study of the process of aneurysm formation. In addition to
      providing a comprehensive method for cardiovascular phenotyping in mice, the
      results of this study confirm that haploinsuffciency is not the underlying
      genetic mechanism in human LDS. 

PMID- 24587009
TI  - Biomarkers of histone deacetylase inhibitor activity in a phase 1 combined
      modality study with radiotherapy.
AB  - BACKGROUND: Following the demonstration that histone deacetylase inhibitors
      enhanced experimental radiation-induced clonogenic suppression, the Pelvic
      Radiation and Vorinostat (PRAVO) phase 1 study, combining fractionated
      radiotherapy with daily vorinostat for pelvic carcinoma, was designed to evaluate
      both clinical and novel biomarker endpoints, the latter relating to
      pharmacodynamic indicators of vorinostat action in clinical radiotherapy.
      PATIENTS AND METHODS: Potential biomarkers of vorinostat radiosensitizing action,
      not simultaneously manifesting molecular perturbations elicited by the radiation
      itself, were explored by gene expression array analysis of study patients'
      peripheral blood mononuclear cells (PBMC), sampled at baseline (T0) and on
      treatment two and 24 hours (T2 and T24) after the patients had received
      vorinostat. RESULTS: This strategy revealed 1,600 array probes that were common
      for the comparisons T2 versus T0 and T24 versus T2 across all of the patients,
      and furthermore, that no significantly differential expression was observed
      between the T0 and T24 groups. Functional annotation analysis of the array data
      showed that a significant number of identified genes were implicated in gene
      regulation, the cell cycle, and chromatin biology. Gene expression was validated
      both in patients' PBMC and in vorinostat-treated human carcinoma xenograft
      models, and transient repression of MYC was consistently observed. CONCLUSION:
      Within the design of the PRAVO study, all of the identified genes showed rapid
      and transient induction or repression and therefore, in principle, fulfilled the
      requirement of being pharmacodynamic biomarkers of vorinostat action in
      fractionated radiotherapy, possibly underscoring the role of MYC in this
      therapeutic setting.

PMID- 24587010
TI  - Cucurbitacin IIb exhibits anti-inflammatory activity through modulating multiple
      cellular behaviors of mouse lymphocytes.
AB  - Cucurbitacin IIb (CuIIb) is one of the major active compounds in Hemsleyadine
      tablets which have been used for clinical treatment of bacillary dysentery,
      enteritis and acute tonsilitis. However, its action mechanism has not been
      completely understood. This study aimed to explore the anti-inflammatory activity
      of CuIIb and its underlying mechanism in mitogen-activated lymphocytes isolated
      from mouse mesenteric lymph nodes. The results showed that CuIIb inhibited the
      proliferation of concanavalin A (Con A)-activated lymphocytes in a time- and dose
      dependent manner. CuIIb treatment arrested their cell cycle in S and G2/M phases
      probably due to the disruption of the actin cytoskeleton and the modulation of
      p27(Kip1) and cyclin levels. Moreover, the surface expression of activation
      markers CD69 and CD25 on Con A-activated CD3(+) T lymphocytes was suppressed by
      CuIIb treatment. Both Con A- and phorbol ester plus ionomycin-induced expression
      of TNF-alpha, IFN-gamma and IL-6 proteins was attenuated upon exposure to CuIIb.
      Mechanistically, CuIIb treatment suppressed the phosphorylation of JNK and Erk1/2
      but not p38 in Con A-activated lymphocytes. Although CuIIb unexpectedly enhanced
      the phosphorylation of IkappaB and NF-kappaB (p65), it blocked the nuclear
      translocation of NF-kappaB (p65). In support of this, CuIIb significantly
      decreased the mRNA levels of IkappaBalpha and TNF-alpha, two target genes of NF
      kappaB, in Con A-activated lymphocytes. In addition, CuIIb downregulated Con A
      induced STAT3 phosphorylation and increased cell apoptosis. Collectively, these
      results suggest that CuIIb exhibits its anti-inflammatory activity through
      modulating multiple cellular behaviors and signaling pathways, leading to the
      suppression of the adaptive immune response. 

PMID- 24587011
TI  - Inhibition of baicalin on metabolism of phenacetin, a probe of CYP1A2, in human
      liver microsomes and in rats.
AB  - Baicalin has been used as mainly bioactive constituent of about 100 kinds of
      traditional Chinese medicines in Chinese pharmacopoeia. The effect of baicalin on
      cytochrome P450 should be paid more attention because baicalin was used widely.
      The aim of this study was to investigate whether baicalin could inhibit CYP1A2 in
      pooled human liver microsomes (HLMs) and in rats in vivo and the gene
      polymorphisms could affect inter-individual variation in IC50 in 28 human livers.
      Phenacetin was used as probe of CYP1A2. Kinetic parameter of CYP1A2 and IC50 of
      baicalin on CYP1A2 to each sample were measured and the common CYP1A2
      polymorphisms (-3860G>A and -163C>A) were genotyped. The results showed that
      baicalin exhibited a mixed-type inhibition in pooled HLMs, with a Ki value of
      25.4 uM. There was substantial variation in Km, Vmax, CLint of CYP1A2 and IC50 of
      baicalin on CYP1A2 (3~10-fold). The range was from 26.6 to 114.8 uM for Km, from
      333 to 1330 pmol.min(-1).mg(-1)protein for Vmax and from 3.8 to 45.3 uL.min(
      1).mg(-1) protein for CLint in HLMs (n = 28). The Mean (range) value of IC50 in
      28 HLMs was 36.3 (18.9 to 56.1) uM. The genotypes of -3860G>A and -163C>A had no
      significant effect on the inhibition of baicalin on CYP1A2. The animal experiment
      results showed that baicalin (450 mg/kg, i.v.) significantly decreased the Cmax
      and CL of phenacetin, and increased C(60 min), t1/2, Vd and AUC (P<0.05). There
      were significant correlations between percentage of control in C(60 min), t1/2,
      CL, AUC of phenacetin and Cmax of baicalin in 11 rats (P<0.05). Protein binding
      experiments in vitro showed that baicalin (0-2000 mg/L) increased the unbound
      phenacetin from 14.5% to 28.3%. In conclusion, baicalin can inhibit the activity
      of CYP1A2 in HLMs and exhibit large inter-individual variation that has no
      relationship with gene polymorphism. Baicalin can change the pharmacokinetics of
      phenacetin in rats.

PMID- 24587012
TI  - Identification of transforming hepatitis B virus S gene nonsense mutations
      derived from freely replicative viruses in hepatocellular carcinoma.
AB  - BACKGROUND & AIMS: The correlation between chronic hepatitis B virus (HBV)
      infection and hepatocellular carcinoma (HCC) has been well-established. But the
      roles of viral factor remain uncertain. Only HBV X gene and nonsense mutations of
      S gene (C-terminal truncation of HBV surface protein) have been demonstrated to
      have transforming activity. Whether they play a significant role in
      hepatocarcinogenesis is still uncertain. METHODS: Twenty-five HBV-related HCC
      patients were positive for hepatitis B core antigen (HBcAg) in the cancerous
      parts of their HCC liver tissues by immunohistochemistry studies, and had
      available tissue for whole HBV genome sequence analysis. The results were
      compared with 25 gender and age-matched HBcAg negative HCCs. Plasmids encoding
      HBV S gene nonsense mutations identified from HBcAg (+) HCC tissue were
      constructed to investigate their cell proliferation, transformation activity and
      the oncogenic potentials by xenograft study and in vivo migration assay. RESULTS:
      HBcAg (+) HCC patients were significantly associated with cirrhosis and small
      tumor size (?2 cm) when compared with HBcAg (-) HCC patients. Southern blot
      analyses revealed freely replicative forms of HBV in the cancerous parts of
      HBcAg(+) HCC. Three nonsense mutations of S gene (sL95*, sW182*, and sL216*) were
      identified in the HBcAg(+) HCC tumor tissues. sW182* and sL216* were recurrently
      found in the 25 HBcAg (-) HCC tumor tissue, too. Functional studies of the above
      3 non-sense mutations all demonstrated higher cell proliferation activities and
      transformation abilities than wild type S, especially sW182*. Tumorigenicity
      analysis by xenograft experiments and in vitro migration assay showed potent
      oncogenic activity of sW182* mutant. CONCLUSIONS: This study has demonstrated
      potent oncogenic activity of nonsense mutations of HBV S gene, suggesting they
      may play an important role in hepatocarcinogenesis.

PMID- 24587013
TI  - Plasma D-dimer predicts short-term poor outcome after acute ischemic stroke.
AB  - OBJECTIVE: Haemostatic biomarkers associated with poor outcome in acute ischemic
      stroke (AIS). The objective of the study was to evaluate the predictive value of
      plasma D-dimer (D-D) on functional outcome at 90-day follow-up from stroke onset.
      METHODS: We conducted a prospective, observational cohort study in the emergency
      department and enrolled 220 patients with AIS. Plasma D-D concentrations,
      determined by a particle-enhanced, immunoturbidimetric assay, were measured. Each
      patient's medical record was reviewed, and demographic, clinical, laboratory and
      neuroimaging information was abstracted. RESULTS: There was a positive
      correlation between levels of D-D and the NIHSS (r = 0.361, p<0.001), and the
      infarct volume (r = 0.449, p<0.001). In the 69 patients with an unfavorable
      functional outcome, D-D levels were higher compared with those in patients with a
      favorable outcome [3.24(IQR, 2.18-4.60)mg/L vs 0.88(IQR, 0.35-1.77) mg/L;
      p<0.001]. After adjusting for all other significant outcome predictors, D-D level
      remained an independent predictor for unfavorable functional outcome and
      mortality with an odds ratio of 2.18 (95% CI, 1.55-2.83), 3.22 (95% CI, 2.05
      6.43); respectively. CONCLUSIONS: D-D levels are a useful tool to predict outcome
      and mortality 90-day after acute ischemic stroke and have a potential to assist
      clinicians.

PMID- 24587014
TI  - Structure and biomechanics of the endothelial transcellular circumferential
      invasion array in tumor invasion.
AB  - Cancer cells breach the endothelium not only through cell-cell junctions but also
      via individual endothelial cells (ECs), or transcellular invasion. The underlying
      EC forms a circular structure around the transcellular invasion pore that is
      dependent on myosin light chain kinase (MLCK) and myosin II regulatory light
      chain (RLC) phosphorylation. Here we offer mechanistic insights into
      transcellular invasive array formation amid persistent tensile force from
      activated EC myosin. Fluorescence recovery after photobleaching (FRAP)
      experiments, sarcomeric distance measurements using super-resolution microscopy
      and electron microscopy provide details about the nature of the myosin II
      invasion array. To probe the relationship between biomechanical forces and the
      tension required to maintain the curvature of contractile filaments, we targeted
      individual actin-myosin fibers at the invasion site for photoablation. We showed
      that adjacent filaments rapidly replace the ablat11ed structures. We propose that
      the transcellular circumferential invasion array (TCIA) provides the necessary
      constraint within the EC to blunt the radial compression from the invading cancer
      cell. 

PMID- 24587015
TI  - Expression of a subset of heat stress induced genes of mycobacterium tuberculosis
      is regulated by 3',5'-cyclic AMP.
AB  - Mycobacterium tuberculosis (Mtb) secretes excess of a second messenger molecule,
      3',5'-cyclic AMP (cAMP), which plays a critical role in the survival of Mtb in
      host macrophages. Although Mtb produces cAMP in abundance, its exact role in the
      physiology of mycobacteria is elusive. In this study we have analyzed the
      expression of 16 adenylate cyclases (ACs) and kinetics of intracellular cAMP
      levels in Mtb during in vitro growth under the regular culture conditions, and
      after exposure to different stress agents. We observed a distinct expression
      pattern of these ACs which is correlated with intracellular cAMP levels.
      Interestingly cAMP levels are significantly elevated in Mtb following heat
      stress, whereas other stress conditions such as oxidative, nitrosative or low pH
      do not affect intracellular cAMP pool in vitro. A significant increase in
      expression by >2-fold of five ACs namely Rv1647, Rv2212, Rv1625c, Rv2488c and
      Rv0386 after heat stress further suggested that cAMP plays an important role in
      controlling Mtb response to heat stress. In the light of these observations,
      effect of exogenous cAMP on global gene expression profile was examined by using
      microarrays. The microarray gene expression analysis demonstrated that cAMP
      regulates expression of a subset of heat stress-induced genes comprising of dnaK,
      grpE, dnaJ, and Rv2025c. Further we performed electrophoretic mobility shift
      assay by using cAMP-receptor protein of Mtb (CRP(M)), which demonstrated that
      CRP(M) specifically recognizes a sequence -301AGCGACCGTCAGCACG-286 in 5'
      untranslated region of dnaK.

PMID- 24587016
TI  - A heritable antiviral RNAi response limits Orsay virus infection in
      Caenorhabditis elegans N2.
AB  - Orsay virus (OrV) is the first virus known to be able to complete a full
      infection cycle in the model nematode species Caenorhabditis elegans. OrV is
      transmitted horizontally and its infection is limited by antiviral RNA
      interference (RNAi). However, we have no insight into the kinetics of OrV
      replication in C. elegans. We developed an assay that infects worms in liquid,
      allowing precise monitoring of the infection. The assay revealed a dual role for
      the RNAi response in limiting Orsay virus infection in C. elegans. Firstly, it
      limits the progression of the initial infection at the step of recognition of
      dsRNA. Secondly, it provides an inherited protection against infection in the
      offspring. This establishes the heritable RNAi response as anti-viral mechanism
      during OrV infections in C. elegans. Our results further illustrate that the
      inheritance of the anti-viral response is important in controlling the infection
      in the canonical wild type Bristol N2. The OrV replication kinetics were
      established throughout the worm life-cycle, setting a standard for further
      quantitative assays with the OrV-C. elegans infection model. 

PMID- 24587017
TI  - Monitoring fibrous scaffold guidance of three-dimensional collagen organisation
      using minimally-invasive second harmonic generation.
AB  - The biological and mechanical function of connective tissues is largely
      determined by controlled cellular alignment and therefore it seems appropriate
      that tissue-engineered constructs should be architecturally similar to the in
      vivo tissue targeted for repair or replacement. Collagen organisation dictates
      the tensile properties of most tissues and so monitoring the deposition of cell
      secreted collagen as the construct develops is essential for understanding tissue
      formation. In this study, electrospun fibres with a random or high degree of
      orientation, mimicking two types of tissue architecture found in the body, were
      used to culture human fibroblasts for controlling cell alignment. The minimally
      invasive technique of second harmonic generation was used with the aim of
      monitoring and profiling the deposition and organisation of collagen at different
      construct depths over time while construct mechanical properties were also
      determined over the culture period. It was seen that scaffold fibre organisation
      affected cell migration and orientation up to 21 days which in turn had an effect
      on collagen organisation. Collagen in random fibrous constructs was deposited in
      alternating configurations at different depths however a high degree of
      organisation was observed throughout aligned fibrous constructs orientated in the
      scaffold fibre direction. Three-dimensional second harmonic generation images
      showed that deposited collagen was more uniformly distributed in random
      constructs but aligned constructs were more organised and had higher intensities.
      The tensile properties of all constructs increased with increasing collagen
      deposition and were ultimately dictated by collagen organisation. This study
      highlights the importance of scaffold architecture for controlling the
      development of well-organised tissue engineered constructs and the usefulness of
      second harmonic generation imaging for monitoring collagen maturation in a
      minimally invasive manner. 

PMID- 24587018
TI  - Afadin regulates puncta adherentia junction formation and presynaptic
      differentiation in hippocampal neurons.
AB  - The formation and remodeling of mossy fiber-CA3 pyramidal cell synapses in the
      stratum lucidum of the hippocampus are implicated in the cellular basis of
      learning and memory. Afadin and its binding cell adhesion molecules, nectin-1 and
      nectin-3, together with N-cadherin, are concentrated at puncta adherentia
      junctions (PAJs) in these synapses. Here, we investigated the roles of afadin in
      PAJ formation and presynaptic differentiation in mossy fiber-CA3 pyramidal cell
      synapses. At these synapses in the mice in which the afadin gene was
      conditionally inactivated before synaptogenesis by using nestin-Cre mice, the
      immunofluorescence signals for the PAJ components, nectin-1, nectin-3 and N
      cadherin, disappeared almost completely, while those for the presynaptic
      components, VGLUT1 and bassoon, were markedly decreased. In addition, these
      signals were significantly decreased in cultured afadin-deficient hippocampal
      neurons. Furthermore, the interevent interval of miniature excitatory
      postsynaptic currents was prolonged in the cultured afadin-deficient hippocampal
      neurons compared with control neurons, indicating that presynaptic functions were
      suppressed or a number of synapse was reduced in the afadin-deficient neurons.
      Analyses of presynaptic vesicle recycling and paired recordings revealed that the
      cultured afadin-deficient neurons showed impaired presynaptic functions. These
      results indicate that afadin regulates both PAJ formation and presynaptic
      differentiation in most mossy fiber-CA3 pyramidal cell synapses, while in a
      considerable population of these neurons, afadin regulates only PAJ formation but
      not presynaptic differentiation. 

PMID- 24587019
TI  - Causality and cointegration analysis between macroeconomic variables and the
      Bovespa.
AB  - The aim of this study is to analyze the causality relationship among a set of
      macroeconomic variables, represented by the exchange rate, interest rate,
      inflation (CPI), industrial production index as a proxy for gross domestic
      product in relation to the index of the Sao Paulo Stock Exchange (Bovespa). The
      period of analysis corresponded to the months from January 1995 to December 2010,
      making a total of 192 observations for each variable. Johansen tests, through the
      statistics of the trace and of the maximum eigenvalue, indicated the existence of
      at least one cointegration vector. In the analysis of Granger (1988) causality
      tests via error correction, it was found that a short-term causality existed
      between the CPI and the Bovespa. Regarding the Granger (1988) long-term
      causality, the results indicated a long-term behaviour among the macroeconomic
      variables with the BOVESPA. The results of the long-term normalized vector for
      the Bovespa variable showed that most signals of the cointegration equation
      parameters are in accordance with what is suggested by the economic theory. In
      other words, there was a positive behaviour of the GDP and a negative behaviour
      of the inflation and of the exchange rate (expected to be a positive
      relationship) in relation to the Bovespa, with the exception of the Selic rate,
      which was not significant with that index. The variance of the Bovespa was
      explained by itself in over 90% at the twelfth month, followed by the country
      risk, with less than 5%.

PMID- 24587020
TI  - Molecular epidemiology of human enterovirus associated with aseptic meningitis in
      Shandong Province, China, 2006-2012.
AB  - BACKGROUND: Human enteroviruses (HEVs) are common causes of acute meningitis.
      However, there is limited information about HEV associated with aseptic
      meningitis in mainland China because it has not been classified as a notifiable
      disease. OBJECTIVES: To characterize the HEVs associated with sporadic aseptic
      meningitis in China and to analyze their genetic features. STUDY DESIGN:
      Cerebrospinal fluid, throat swab and feces specimens were collected from patients
      with aseptic meningitis in 5 sentinel hospitals in Shandong Province, China
      between 2006 and 2012. Virological investigation (viral isolation and molecular
      identification) and phylogenetic analysis were performed. RESULTS: A total of 437
      hospitalized patients were reported, and enteroviruses were detected in the
      specimens from 84 patients (19.2%) and were identified into 17 serotypes. The
      nine main serotypes were echovirus (E) 30 (27.4%), EV71 (13.1%), coxsackievirus
      (CV) B1 (9.5%), CVB3 (7.1%), CVB5 (7.1%), E6 (7.1%), E9 (7.1%), CVA9 (6.0%), and
      CVA10 (3.6%). Monthly distribution of isolated enteroviruses revealed a major
      peak in summer-fall season and a small second peak in winter constituted totally
      by EV71. Sequence analysis on VP1 coding region suggested Shandong strains had
      great genetic divergence with isolates from other countries. CONCLUSIONS:
      Multiple serotypes were responsible for enterovirus meningitis in mainland China.
      Aseptic meningitis caused by EV71 and coxsackie A viruses-the predominant
      pathogens for the hand, foot, and mouth disease-is currently an important concern
      in mainland China.

PMID- 24587021
TI  - Substrate stiffness regulates filopodial activities in lung cancer cells.
AB  - Microenvironment stiffening plays a crucial role in tumorigenesis. While
      filopodia are generally thought to be one of the cellular mechanosensors for
      probing environmental stiffness, the effects of environmental stiffness on
      filopodial activities of cancer cells remain unclear. In this work, we
      investigated the filopodial activities of human lung adenocarcinoma cells CL1-5
      cultured on substrates of tunable stiffness using a novel platform. The platform
      consists of an optical system called structured illumination nano-profilometry,
      which allows time-lapsed visualization of filopodial activities without
      fluorescence labeling. The culturing substrates were composed of polyvinyl
      chloride mixed with an environmentally friendly plasticizer to yield Young's
      modulus ranging from 20 to 60 kPa. Cell viability studies showed that the
      viability of cells cultured on the substrates was similar to those cultured on
      commonly used elastomers such as polydimethylsiloxane. Time-lapsed live cell
      images were acquired and the filopodial activities in response to substrates with
      varying degrees of stiffness were analyzed. Statistical analyses revealed that
      lung cancer cells cultured on softer substrates appeared to have longer
      filopodia, higher filopodial densities with respect to the cellular perimeter,
      and slower filopodial retraction rates. Nonetheless, the temporal analysis of
      filopodial activities revealed that whether a filopodium decides to extend or
      retract is purely a stochastic process without dependency on substrate stiffness.
      The discrepancy of the filopodial activities between lung cancer cells cultured
      on substrates with different degrees of stiffness vanished when the myosin II
      activities were inhibited by treating the cells with blebbistatin, which suggests
      that the filopodial activities are closely modulated by the adhesion strength of
      the cells. Our data quantitatively relate filopodial activities of lung cancer
      cells with environmental stiffness and should shed light on the understanding and
      treatment of cancer progression and metastasis. 

PMID- 24587022
TI  - Perceptual simulation in gender categorization: associations between gender,
      vertical height, and spatial size.
AB  - The current studies extend perceptual symbol systems theory to the processing of
      gender categorization by revealing that gender categorization recruits perceptual
      simulations of spatial height and size dimensions. In study 1, categorization of
      male faces were faster when the faces were in the "up" (i.e., higher on the
      vertical axis) rather than the "down" (i.e., lower on the vertical axis) position
      and vice versa for female face categorization. Study 2 found that responses to
      male names depicted in larger font were faster than male names depicted in
      smaller font, whereas opposite response patterns were given for female names.
      Study 3 confirmed that the effect in Study 2 was not due to metaphoric
      relationships between gender and social power. Together, these findings suggest
      that representation of gender (social categorization) also involves processes of
      perceptual simulation. 

PMID- 24587023
TI  - Multiple ITS copies reveal extensive hybridization within Rheum (Polygonaceae), a
      genus that has undergone rapid radiation.
AB  - BACKGROUND: During adaptive radiation events, characters can arise multiple times
      due to parallel evolution, but transfer of traits through hybridization provides
      an alternative explanation for the same character appearing in apparently non
      sister lineages. The signature of hybridization can be detected in incongruence
      between phylogenies derived from different markers, or from the presence of two
      divergent versions of a nuclear marker such as ITS within one individual.
      METHODOLOGY/PRINCIPAL FINDINGS: In this study, we cloned and sequenced ITS
      regions for 30 species of the genus Rheum, and compared them with a cpDNA
      phylogeny. Seven species contained two divergent copies of ITS that resolved in
      different clades from one another in each case, indicating hybridization events
      too recent for concerted evolution to have homogenised the ITS sequences.
      Hybridization was also indicated in at least two further species via incongruence
      in their position between ITS and cpDNA phylogenies. None of the ITS sequences
      present in these nine species matched those detected in any other species, which
      provides tentative evidence against recent introgression as an explanation. Rheum
      globulosum, previously indicated by cpDNA to represent an independent origin of
      decumbent habit, is indicated by ITS to be part of clade of decumbent species,
      which acquired cpDNA of another clade via hybridization. However decumbent and
      glasshouse morphology are confirmed to have arisen three and two times,
      respectively. CONCLUSIONS: These findings suggested that hybridization among QTP
      species of Rheum has been extensive, and that a role of hybridization in
      diversification of Rheum requires investigation.

PMID- 24587024
TI  - Murine experimental autoimmune encephalomyelitis is diminished by treatment with
      the angiogenesis inhibitors B20-4.1.1 and angiostatin (K1-3).
AB  - Angiogenesis is the formation of new blood vessels form pre-existing vasculature
      whose contribution to inflammatory conditions of the Central Nervous System is
      being studied in order to generate novel therapeutic targets. This study is the
      first to investigate the impact of two particular angiogenesis inhibitors on
      murine Experimental Autoimmune Encephalomyelitis (EAE), an inflammatory disease
      that mimics aspects of the human disease Multiple Sclerosis. The inhibitors were
      chosen to reduce angiogenesis by complimentary means. Extrinsic factors were
      targeted with B20-4.1.1 through its ability to bind to murine Vascular
      Endothelial Growth Factor (VEGF). Vascular processes connected to angiogenesis
      were targeted directly with K(1-3), the first three kringle domains of
      angiostatin. Mice treated with B20-4.1.1 and K(1-3) from onset of signs had
      reduced clinical scores 18-21 days after EAE induction. Both agents suppressed
      spinal cord angiogenesis without effect on local VEGF expression. B20-4.1.1
      reduced spinal cord vascular permeability while K(1-3) had no effect. T cell
      infiltration into the spinal cord at day 21 was unaffected by either treatment.
      B20-4.1.1 reduced peripheral T cell proliferation while K(1-3) had no effect.
      Lymphoid cells from treated mice produced reduced levels of the T helper-17 (Th
      17) cell cytokine interleukin (IL)-17 with no effect on the Th-1 cytokine
      interferon (IFN)-gamma or Th-2 cytokine IL-4. However, when both drugs were added
      in vitro to naive T cells or to antigen stimulated T cells from mice with
      untreated EAE they had no effect on proliferation or levels of IL-17 or IFN
      gamma. We conclude that these angiogenesis inhibitors mitigate EAE by both
      suppressing spinal cord angiogenesis and reducing peripheral T cell activation. 

PMID- 24587026
TI  - Recognizing induced emotions of happiness and sadness from dance movement.
AB  - Recent research revealed that emotional content can be successfully decoded from
      human dance movement. Most previous studies made use of videos of actors or
      dancers portraying emotions through choreography. The current study applies
      emotion induction techniques and free movement in order to examine the
      recognition of emotional content from dance. Observers (N = 30) watched a set of
      silent videos showing depersonalized avatars of dancers moving to an emotionally
      neutral musical stimulus after emotions of either sadness or happiness had been
      induced. Each of the video clips consisted of two dance performances which were
      presented side-by-side and were played simultaneously; one of a dancer in the
      happy condition and one of the same individual in the sad condition. After every
      film clip, the observers were asked to make forced-choices concerning the
      emotional state of the dancer. Results revealed that observers were able to
      identify the emotional state of the dancers with a high degree of accuracy.
      Moreover, emotions were more often recognized for female dancers than for their
      male counterparts. In addition, the results of eye tracking measurements unveiled
      that observers primarily focus on movements of the chest when decoding emotional
      information from dance movement. The findings of our study show that not merely
      portrayed emotions, but also induced emotions can be successfully recognized from
      free dance movement. 

PMID- 24587027
TI  - Divergent distribution of the sensor kinase CosS in non-thermotolerant
      campylobacter species and its functional incompatibility with the response
      regulator CosR of Campylobacter jejuni.
AB  - Two-component signal transduction systems are commonly composed of a sensor
      histidine kinase and a cognate response regulator, modulating gene expression in
      response to environmental changes through a phosphorylation-dependent process.
      CosR is an OmpR-type response regulator essential for the viability of
      Campylobacter jejuni, a major foodborne pathogenic species causing human
      gastroenteritis. Although CosR is a response regulator, its cognate sensor kinase
      has not been identified in C. jejuni. In this study, DNA sequence analysis of the
      cosR flanking regions revealed that a gene encoding a putative sensor kinase,
      which we named cosS, is prevalent in non-thermotolerant Campylobacter spp., but
      not in thermotolerant campylobacters. Phosphorylation assays indicated that C.
      fetus CosS rapidly autophosphorylates and then phosphorylates C. fetus CosR,
      suggesting that the CosRS system constitutes a paired two-component signal
      transduction system in C. fetus. However, C. fetus CosS does not phosphorylate C.
      jejuni CosR, suggesting that CosR may have different regulatory cascades between
      thermotolerant and non-thermotolerant Campylobacter species. Comparison of CosR
      homolog amino acid sequences showed that the conserved phosphorylation residue
      (D51), which is present in all non-thermotolerant Campylobacter spp., is absent
      from the CosR homologs of thermotolerant Campylobacter species. However, C.
      jejuni CosR was not phosphorylated by C. fetus CosS even after site-directed
      mutagenesis of N51D, implying that C. jejuni CosR may possibly function
      phosphorylation-independently. In addition, the results of cosS mutational
      analysis indicated that CosS is not associated with the temperature dependence of
      the Campylobacter spp. despite its unique divergent distribution only in non
      thermotolerant campylobacters. The findings in this study strongly suggest that
      thermotolerant and non-thermotolerant Campylobacter spp. have different signal
      sensing mechanisms associated with the CosR regulation. 

PMID- 24587025
TI  - Evidence for a Golgi-to-endosome protein sorting pathway in Plasmodium
      falciparum.
AB  - During the asexual intraerythrocytic stage, the malaria parasite Plasmodium
      falciparum must traffic newly-synthesized proteins to a broad array of
      destinations within and beyond the parasite's plasma membrane. In this study, we
      have localized two well-conserved protein components of eukaryotic endosomes, the
      retromer complex and the small GTPase Rab7, to define a previously-undescribed
      endosomal compartment in P. falciparum. Retromer and Rab7 co-localized to a small
      number of punctate structures within parasites. These structures, which we refer
      to as endosomes, lie in close proximity to the Golgi apparatus and, like the
      Golgi apparatus, are inherited by daughter merozoites. However, the endosome is
      clearly distinct from the Golgi apparatus as neither retromer nor Rab7
      redistributed to the endoplasmic reticulum upon brefeldin A treatment. Nascent
      rhoptries (specialized secretory organelles required for invasion) developed
      adjacent to endosomes, an observation that suggests a role for the endosome in
      rhoptry biogenesis. A P. falciparum homolog of the sortilin family of protein
      sorting receptors (PfSortilin) was localized to the Golgi apparatus. Together,
      these results elaborate a putative Golgi-to-endosome protein sorting pathway in
      asexual blood stage parasites and suggest that one role of retromer is to mediate
      the retrograde transport of PfSortilin from the endosome to the Golgi apparatus. 

PMID- 24587028
TI  - Infective endocarditis with antineutrophil cytoplasmic antibody: report of 13
      cases and literature review.
AB  - OBJECTIVE: Chronic infections tend to induce the production of antineutrophil
      cytoplasmic antibody (ANCA). Infective endocarditis (IE) has been reported to
      exhibit positive ANCA tests and to mimic ANCA-associated vasculitis, which may
      lead to a misdiagnosis and inappropriate treatment. The aim of this study was to
      clarify whether there is any difference in the clinical features between ANCA
      positive IE and ANCA-negative IE. METHODS: A retrospective study was carried out
      on 39 IE patients whose proteinase 3 (PR3)-ANCA and myeloperoxidase (MPO)-ANCA
      levels were measured. After dividing the patients into ANCA-positive and ANCA
      negative IE, we compared their clinical features. RESULTS: we compared 13 ANCA
      positive IE patients with 26 ANCA-negative IE patients. All 13 ANCA-positive IE
      patients were proteinase-3-ANCA positive. Compared with the ANCA-negative IE
      group, the prevalence of edema of the lower extremities, the serum lactate
      dehydrogenase (LDH) level and positive blood cultures rate were higher in ANCA
      positive IE group, but there was no significant difference in other clinical
      features. CONCLUSION: Therefore, if a patient presents with fever, arthralgia,
      skin rash and is ANCA-positive, appropriate steps should be taken to exclude
      infection (especially IE) before confirming the diagnosis of ANCA-associated
      vasculitis and embarking on long-term immunosuppressive therapy.

PMID- 24587029
TI  - Outcomes of sentinel lymph node dissection alone vs. axillary lymph node
      dissection in early stage invasive lobular carcinoma: a retrospective study of
      the surveillance, epidemiology and end results (SEER) database.
AB  - BACKGROUND: The American College of Surgeons Oncology Group (ACOSOG) Z0011 trial
      demonstrated no difference in local-regional recurrence (LRR), disease-specific
      survival (DSS) or overall survival (OS) for sentinel lymph node dissection (SLND)
      and completion axillary lymph node dissection (ALND) among patients undergoing
      breast-conserving therapy for clinical T1-T2, N0 breast cancer with 1 or 2
      positive SLNs. However, Only 7% of study participants had invasive lobular
      carcinoma (ILC). Because ILC has a different pattern of metastases, frequently
      presenting as small foci requiring immunohistochemistry for detection, the
      applicability of ACOSOG Z0011 trial data to ILC patients is unclear. STUDY
      DESIGN: We identified all ILC patients in the Surveillance, Epidemiology, and End
      Results (SEER) database (1998-2009) who met the ACOSOG Z0011 eligibility
      criteria. Patients were evaluated on the basis of the extent of axillary surgery
      (SLND alone or ALND), and the clinical outcomes of these 2 groups were compared.
      RESULTS: 1269 patients (393 SLND and 876 ALND) were identified from the SEER
      database. At a median follow-up time of 71 months, there were no differences in
      OS or disease-specific survival between the two groups. CONCLUSION: SLND alone
      may result in outcomes comparable to those achieved with ALND for patients with
      early-stage ILC who meet the ACOSOG Z0011 eligibility criteria.

PMID- 24587030
TI  - New integrated strategy emphasizing infection source control to curb
      Schistosomiasis japonica in a marshland area of Hubei Province, China: findings
      from an eight-year longitudinal survey.
AB  - BACKGROUND: Schistosomiasis remains a major public health problem in China. The
      major endemic foci are the lake and marshland regions of southern China,
      particularly the regions along the middle and lower reach of the Yangtze River in
      four provinces (Hubei, Hunan, Jiangxi, and Anhui). The purpose of our study is to
      assess the effect of a new integrated strategy emphasizing infection source
      control to curb schistosomiasis in marshland regions. METHODS: In a longitudinal
      study, we implemented an integrated control strategy emphasizing infection source
      control in 16 villages from 2005 through 2012 in marshland regions of Hubei
      province. The interventions included removing cattle from snail-infested
      grasslands, providing farmers with mechanized farm equipment, improving
      sanitation by supplying tap water, building lavatories and latrines, praziquantel
      chemotherapy, controlling snails, and environmental modification. RESULTS:
      Following the integrated control strategy designed to reduce the role of bovines
      and humans as sources of Schistosoma japonicum infection, the prevalence of human
      S. japonicum infection declined from 1.7% in 2005 to 0.4% in 2012 (P<0.001).
      Reductions were also observed in both sexes, across all age groups, and among
      high risk occupations. Moreover, the prevalence of bovine S. japonicum infection
      decreased from 11.7% in 2005 to 0.6% in 2012 (P<0.001). In addition, all the 16
      villages achieved the national criteria of infection control in 2008. CONCLUSION:
      Our findings indicate that the integrated strategy was likely effective in
      controlling the transmission of S. japonicum in marshland regions in China.

PMID- 24587031
TI  - Socio-ecological risk factors for prime-age adult death in two coastal areas of
      Vietnam.
AB  - BACKGROUND: Hierarchical spatial models enable the geographic and ecological
      analysis of health data thereby providing useful information for designing
      effective health interventions. In this study, we used a Bayesian hierarchical
      spatial model to evaluate mortality data in Vietnam. The model enabled
      identification of socio-ecological risk factors and generation of risk maps to
      better understand the causes and geographic implications of prime-age (15 to less
      than 45 years) adult death. METHODS AND FINDINGS: The study was conducted in two
      sites: Nha Trang and Hue in Vietnam. The study areas were split into 500*500
      meter cells to define neighborhoods. We first extracted socio-demographic data
      from population databases of the two sites, and then aggregated the data by
      neighborhood. We used spatial hierarchical model that borrows strength from
      neighbors for evaluating risk factors and for creating spatially smoothed risk
      map after adjusting for neighborhood level covariates. The Markov chain Monte
      Carlo procedure was used to estimate the parameters. Male mortality was more than
      twice the female mortality. The rates also varied by age and sex. The most
      frequent cause of mortality was traffic accidents and drowning for men and
      traffic accidents and suicide for women. Lower education of household heads in
      the neighborhood was an important risk factor for increased mortality. The
      mortality was highly variable in space and the socio-ecological risk factors are
      sensitive to study site and sex. CONCLUSION: Our study suggests that lower
      education of the household head is an important predictor for prime age adult
      mortality. Variability in socio-ecological risk factors and in risk areas by sex
      make it challenging to design appropriate intervention strategies aimed at
      decreasing prime-age adult deaths in Vietnam.

PMID- 24587032
TI  - Rab27a was identified as a prognostic biomaker by mRNA profiling, correlated with
      malignant progression and subtype preference in gliomas.
AB  - PURPOSE: Rab27a belongs to the Rab small GTPase superfamily. The protein is
      membrane-bound and may be involved in protein transport and small GTPase-mediated
      signal transduction. Mutations in this gene are associated with Griscelli
      syndrome type 2. However, the prognostic and molecular features of gliomas with
      Rab27a expression are still unclear. EXPERIMENTAL DESIGN: We used a whole-genome
      mRNA expression microarray dataset of 220 glioma samples from the Chinese Glioma
      Genome Atlas (CGGA) database (http://www.cgga.org.cn) as a discovery set. In this
      set, 220 gliomas, consisting of 97 WHO Grade II gliomas, 34 WHO Grade III
      gliomas, and 89 WHO Grade IV gliomas, were analyzed using the Kaplan-Meier
      method. To validate the protein expression of Rab27a, we assayed another 162
      glioma samples by immunohistochemistry. Three additional datasets were obtained
      as validation sets. Gene ontology (GO) analysis and gene set variation analysis
      (GSVA) were used for the functional annotation of Rab27a in 89 WHO Grade IV
      gliomas. RESULTS: Rab27a was significantly associated with grade progression and
      high mortality in all grades of glioma in the discovery set. Rab27a also showed a
      mesenchymal subtype, G3 subtype and isocitrate dehydrogenase 1 (IDH1) wild-type
      preference and association with migration. The 3 validation datasets revealed
      similar findings. Rab27a was more highly expressed in gliomas than in normal
      brain tissues, and its expression increased with glioma grade progression.
      CONCLUSIONS: Rab27a expression was significantly associated with grade
      progression and worse prognosis in all grades of gliomas, suggesting Rab27a as a
      novel biomarker with potentially important therapeutic implications.

PMID- 24587033
TI  - An improved single cell ultrahigh throughput screening method based on in vitro
      compartmentalization.
AB  - High-throughput screening is a key technique in discovery and engineering of
      enzymes. In vitro compartmentalization based fluorescence-activated cell sorting
      (IVC-FACS) has recently emerged as a powerful tool for ultrahigh-throughput
      screening of biocatalysts. However, the accuracy of current IVC-FACS assays is
      severely limited by the wide polydispersity of micro-reactors generated by
      homogenizing. Here, an improved protocol based on membrane-extrusion technique
      was reported to generate the micro-reactors in a more uniform manner. This
      crucial improvement enables ultrahigh-throughput screening of enzymatic activity
      at a speed of >108 clones/day with an accuracy that could discriminate as low as
      two-fold differences in enzymatic activity inside the micro-reactors, which is
      higher than similar IVC-FACS systems ever have reported. The enzymatic reaction
      in the micro-reactors has very similar kinetic behavior compared to the bulk
      reaction system and shows wide dynamic range. By using the modified IVC-FACS, E.
      coli cells with esterase activity could be enriched 330-fold from large excesses
      of background cells through a single round of sorting. The utility of this new
      IVC-FACS system was further illustrated by the directed evolution of thermophilic
      esterase AFEST. The catalytic activity of the very efficient esterase was further
      improved by ~2-fold, resulting in several improved mutants with k(cat)/K(M)
      values approaching the diffusion-limited efficiency of ~108 M-1s-1.

PMID- 24587034
TI  - Lost in transition: HIV prevalence and correlates of infection among young people
      living in post-emergency phase transit camps in Gulu District, Northern Uganda.
AB  - OBJECTIVE: Little is known about HIV infection and the related vulnerabilities of
      young people living in resource-scarce, post-emergency transit camps that are now
      home to thousands of Internally Displaced Persons (IDPs) following two decades of
      war in northern Uganda. The objective of this analysis was to assess the
      prevalence and correlates of HIV infection among young people living in post
      conflict transition in Gulu District, northern Uganda. METHODS: In 2010, a cross
      sectional demographic and behavioural survey was conducted in two of Gulu
      District's sub-counties with 384 purposively selected transit camp residents aged
      15 to 29 years. Biological specimens were collected for rapid HIV testing in the
      field and confirmatory laboratory testing. Multivariable logistic regression
      identified independent determinants of HIV infection. RESULTS: HIV prevalence was
      alarmingly high at 12.8% (95% CI: 9.6%, 16.5%). The strongest determinant of HIV
      infection among young people was a non-consensual sexual debut (adjusted odds
      ratio [AOR], 9.88; 95% CI: 1.70-18.06). Residing in Awach sub-county (AOR, 2.93;
      95% CI: 1.28-6.68), experiencing STI symptoms in the previous 12 months (AOR,
      2.36; 95% CI: 1.43-6.17), and practicing dry sex (AOR, 2.31; 95% CI: 1.04-5.13)
      were other key determinants of HIV infection. CONCLUSIONS: Study findings
      contribute to filling an important gap in epidemiological evidence and are useful
      for planning public health interventions in northern Uganda that effectively
      target young people in post-conflict transition and support them in the
      resettlement process. Findings serve to recommend reaching beyond traditional
      prevention programming in a way more effectively beneficial to young people in
      post-conflict settings by developing population-specific responses sensitive to
      local contexts and sufficient to address the underlying causes of the complex
      risk factors influencing the spread of HIV.

PMID- 24587035
TI  - Prevalence and costs of multimorbidity by deprivation levels in the basque
      country: a population based study using health administrative databases.
AB  - BACKGROUND: Multimorbidity is a major challenge for healthcare systems. However,
      currently, its magnitude and impact in healthcare expenditures is still mostly
      unknown. OBJECTIVE: To present an overview of the prevalence and costs of
      multimorbidity by socioeconomic levels in the whole Basque population. METHODS:
      We develop a cross-sectional analysis that includes all the inhabitants of the
      Basque Country (N=2,262,698). We utilize data from primary health care electronic
      medical records, hospital admissions, and outpatient care databases,
      corresponding to a 4 year period. Multimorbidity was defined as the presence of
      two or more chronic diseases out of a list of 52 of the most important and common
      chronic conditions given in the literature. We also use socioeconomic and
      demographic variables such as age, sex, individual healthcare cost, and
      deprivation level. Predicted adjusted costs were obtained by log-gamma regression
      models. RESULTS: Multimorbidity of chronic diseases was found among 23.61% of the
      total Basque population and among 66.13% of those older than 65 years.
      Multimorbid patients account for 63.55% of total healthcare expenditures.
      Prevalence of multimorbidity is higher in the most deprived areas for all age and
      sex groups. The annual cost of healthcare per patient generated for any chronic
      disease depends on the number of coexisting comorbidities, and varies from 637 ?
      for the first pathology in average to 1,657 ? for the ninth one. CONCLUSION:
      Multimorbidity is very common for the Basque population and its prevalence rises
      in age, and unfavourable socioeconomic environment. The costs of care for chronic
      patients with several conditions cannot be described as the sum of their
      individual pathologies in average. They usually increase dramatically according
      to the number of comorbidities. Given the ageing population, multimorbidity and
      its consequences should be taken into account in healthcare policy, the
      organization of care and medical research.

PMID- 24587037
TI  - Association between time of pay-for-performance for patients and community health
      services use by chronic patients.
AB  - BACKGROUND: Pay-for-performance for patients is a cost-effective means of
      improving health behaviours. This study examined the association between the pay
      time for performance for patients and CHS use by chronic patients. METHODS: A
      cross-sectional study was undertaken to estimate distribution characteristics of
      CHS use in 2011 and collect data of socio-demographic characteristics (sex, age,
      education level, occupation, disposable personal income in 2011, distance between
      home and community health agency), chronic disease number, and time of pay-for
      performance for patients. Participants were 889 rural adults with hypertension or
      type II diabetes aged 35 and above. Standardized CHS use means chronic patients
      use CHS at least once per quarter. RESULTS: Patients who received incentives
      prior to services had 2.724 times greater odds of using standardized CHS than
      those who received incentives after services (95%CI, 1.986-3.736, P<0.001). For
      all subgroups (socio-demographic characteristics and chronic disease number),
      patients who received incentives prior to services were more likely to use
      standardized CHS than those receiving incentives after services. CONCLUSIONS: Pay
      time for performance for patients was associated with CHS use by chronic
      patients. Patients receiving incentive prior to services were more likely to use
      standardized CHS. And pay time should not be ignored when the policy on pay-for
      performance for patients is designed.

PMID- 24587036
TI  - Insight into buffalo (Bubalus bubalis) RIG1 and MDA5 receptors: a comparative
      study on dsRNA recognition and in-vitro antiviral response.
AB  - RIG1 and MDA5 have emerged as important intracellular innate pattern recognition
      receptors that recognize viral RNA and mediate cellular signals controlling Type
      I interferon (IFN-I) response. Buffalo RIG1 and MDA5 genes were investigated to
      understand the mechanism of receptor induced antiviral response. Sequence
      analysis revealed that RIG1 and MDA5 maintain a domain arrangement that is common
      in mammals. Critical binding site residues of the receptors are evolutionary
      conserved among mammals. Molecular dynamics simulations suggested that RIG1 and
      MDA5 follow a similar, if not identical, dsRNA binding pattern that has been
      previously reported in human. Moreover, binding free energy calculation revealed
      that MDA5 had a greater affinity towards dsRNA compared to RIG1. Constitutive
      expressions of RLR genes were ubiquitous in different tissues without being
      specific to immune organs. Poly I:C stimulation induced elevated expressions of
      IFN-beta and IFN-stimulated genes (ISGs) through interferon regulatory factors
      (IRFs) mediated pathway in buffalo foetal fibroblast cells. The present study
      provides crucial insights into the structure and function of RIG1 and MDA5
      receptors in buffalo. 

PMID- 24587038
TI  - Detecting potential adverse reactions of sulpiride in schizophrenic patients by
      prescription sequence symmetry analysis.
AB  - PURPOSE: Previous studies have demonstrated sulpiride to be significantly more
      effective than haloperidol, risperidone and olanzapine in schizophrenic
      treatment; however, only limited information is available on the potential risks
      associated with sulpiride treatment. This study attempts to provide information
      on the potential risks of sulpiride treatment of schizophrenia, especially with
      regard to unexpected adverse effects. MATERIALS AND METHODS: Patients with
      schizophrenia aged 18 and older, newly prescribed with a single antipsychotic
      medication from the National Health Insurance Research Database of Taiwan in the
      period from 2003 to 2010 were included. A within-subject comparison method,
      prescription sequence symmetry analysis (PSSA) was employed to efficiently
      identify potential causal relationships while controlling for potential selection
      bias. RESULTS: A total of 5,750 patients, with a mean age of 39, approximately
      half of whom were male, constituted the study cohort. The PSSA found that
      sulpiride was associated with EPS (adjusted SR, 1.73; 95% CI, 1.46-2.06) and
      hyperprolactinemia (12.04; 1.59-91.2). In comparison, EPS caused by haloperidol
      has a magnitude of 1.99 when analyzed with PSSA, and hyperprolactinemia caused by
      amisulpride has a magnitude of 8.05, respectively. Another finding was the
      unexpected increase in the use of stomatological corticosteroids, emollient
      laxatives, dermatological preparations of corticosteroids, quinolone
      antibacterials, and topical products for joint and muscular pain, after
      initiation of sulpiride treatment. CONCLUSIONS: We found sulpiride to be
      associated with an increased risk of EPS and hyperprolactinemia, and the
      potential risk could be as high as that induced by haloperidol and amisulpride,
      respectively. Additionally, our study provides grounds for future investigations
      into the associations between sulpiride and the increased use of additional drugs
      for managing adverse effects, including stomatological, dermatological, and
      musculoskeletal or joint side effects, constipation, and pneumonia.

PMID- 24587039
TI  - The homologous carboxyl-terminal domains of microtubule-associated protein 2 and
      TAU induce neuronal dysfunction and have differential fates in the evolution of
      neurofibrillary tangles.
AB  - Microtubule-associated protein 2 (MAP2) and Tau are abundant neuronal microtubule
      associated proteins. Both proteins have highly homologous carboxyl-terminal
      sequences that function as microtubule-binding domains. Whereas Tau is widely
      accepted as a pathoetiological factor in human tauopathies, including Alzheimer's
      disease (AD), it is not known whether there is a relationship between MAP2 and
      tauopathy. To better understand the pathological roles of MAP2 and Tau, we
      compared their behaviors in transgenic Caenorhabditis elegans in which MAP2 or
      Tau was expressed pan-neuronally. Both MAP2 and Tau elicited severe neuronal
      dysfunction and neuritic abnormalities, despite the absence of detergent
      insoluble aggregates in worm neurons. Biochemical analysis revealed that the
      expressed MAP2 or Tau in worms was highly phosphorylated and did not bind to
      microtubules. Newly raised antibodies to MAP2 that effectively distinguished
      between the highly homologous carboxyl-terminal sequences of MAP2 and Tau showed
      that MAP2 was not involved in the growth process of neurofibrillary tangles in
      the AD brain. These results indicate that Tau and MAP2 have different fates in
      the inclusion formation and raise the possibility that MAP2 plays a significant
      role in neurotoxicity in the AD brain despite the absence of MAP2-aggregates. 

PMID- 24587040
TI  - Reproducibility of magnetic resonance perfusion imaging.
AB  - Dynamic MR biomarkers (T2*-weighted or susceptibility-based and T1-weighted or
      relaxivity-enhanced) have been applied to assess tumor perfusion and its response
      to therapies. A significant challenge in the development of reliable biomarkers
      is a rigorous assessment and optimization of reproducibility. The purpose of this
      study was to determine the measurement reproducibility of T1-weighted dynamic
      contrast-enhanced (DCE)-MRI and T2*-weighted dynamic susceptibility contrast
      (DSC)-MRI with two contrast agents (CA) of different molecular weight (MW):
      gadopentetate (Gd-DTPA, 0.5 kDa) and Gadomelitol (P792, 6.5 kDa). Each contrast
      agent was tested with eight mice that had subcutaneous MDA-MB-231 breast
      xenograft tumors. Each mouse was imaged with a combined DSC-DCE protocol three
      times within one week to achieve measures of reproducibility. DSC-MRI results
      were evaluated with a contrast to noise ratio (CNR) efficiency threshold. There
      was a clear signal drop (>95% probability threshold) in the DSC of normal tissue,
      while signal changes were minimal or non-existent (<95% probability threshold) in
      tumors. Mean within-subject coefficient of variation (wCV) of relative blood
      volume (rBV) in normal tissue was 11.78% for Gd-DTPA and 6.64% for P792. The
      intra-class correlation coefficient (ICC) of rBV in normal tissue was 0.940 for
      Gd-DTPA and 0.978 for P792. The inter-subject correlation coefficient was 0.092.
      Calculated K(trans) from DCE-MRI showed comparable reproducibility (mean wCV,
      5.13% for Gd-DTPA, 8.06% for P792). ICC of K(trans) showed high intra-subject
      reproducibility (ICC = 0.999/0.995) and inter-subject heterogeneity (ICC =
      0.774). Histograms of K(trans) distributions for three measurements had high
      degrees of overlap (sum of difference of the normalized histograms <0.01). These
      results represent homogeneous intra-subject measurement and heterogeneous inter
      subject character of biological population, suggesting that perfusion MRI could
      be an imaging biomarker to monitor or predict response of disease.

PMID- 24587041
TI  - Use of antithrombotics after hemorrhagic transformation in acute ischemic stroke.
AB  - BACKGROUNDS: There have been neither appropriate guidelines nor clinical studies
      about the use of antithrombotics after hemorrhagic transformation (HT). We sought
      to find whether the use of antithrombotics after hemorrhagic infarction might be
      associated with aggravation of HT and neurological deterioration. METHODS: This
      retrospective study included prospectively registered consecutive patients with
      acute ischemic stroke and HT in our tertiary stroke center. We focused on the
      hemorrhagic infarction. Aggravation of HT was defined as either enlargement of
      the original HT or newly developed HT within the infarcted area by visual
      analysis. We analyzed relationships between antithrombotics and HT, and
      neurological deterioration after HT in patients with hemorrhagic infarction. In
      addition, we assessed composite outcomes including neurological deterioration,
      vascular events, and death at 1 month after HT. We analyzed relationships between
      antithrombotics after discharge and composite outcomes within 1 month after HT.
      RESULTS: 222 patients were finally analyzed. Of the 150 patients with hemorrhagic
      infarction, 75 (50.0%) were type 1. The use of warfarin after detection of
      hemorrhagic infarction more frequently increased aggravation of HT than did the
      use of antiplatelets (4 of 24 vs 3 of 69; p = 0.094), but neither warfarin nor
      antiplatelets caused more HT than no medication. In addition, the use of
      antithrombotics after hemorrhagic infarction was not significantly associated
      with neurological deterioration after HT. The frequency of composite events at 1
      months was significantly lower in patients treated with antithrombotics than
      those treated without (p = 0.041). CONCLUSION: In conclusion, the results of this
      study suggest that antithrombotics can safely be used after hemorrhagic
      infarction and may not be associated with neurological deterioration and
      aggravation of HT. Further studies are needed to confirm our results.

PMID- 24587042
TI  - Elevated levels of MYB30 in the phloem accelerate flowering in Arabidopsis
      through the regulation of FLOWERING LOCUS T.
AB  - In Arabidopsis thaliana, the R2R3 MYB-like transcription factor MYB30 is a
      positive regulator of the pathogen-induced hypersensitive response and of
      brassinosteroid and abscisic acid signaling. Here, we show that MYB30 expressed
      under the control of the strong phloem-specific SUC2 promoter accelerates
      flowering both in long and short days. Early flowering is mediated by elevated
      expression of flowering locus T (FT), which can be observed in the absence and
      presence of CONSTANS (CO), the main activator of FT. CO-independent activation by
      high MYB30 expression results in FT levels that remain below those observed in
      the wild-type plants, which show an additive CO-dependent activation. In
      contrast, twin sister of FT (TSF) is repressed in plants expressing high levels
      of MYB30 in the phloem. In transient assays, MYB30 and CO additively increase the
      activity of a reporter construct driven by a 1 kb FT promoter. Acceleration of
      flowering by MYB30 does not require the presence of salicylic acid and is
      independent of FLC. Taken together, increased levels of MYB30, which was reported
      to be induced in response to the perception of pathogens, can accelerate
      flowering and MYB30 may thus be a candidate to mediate cross-talk between gene
      networks involved in biotic stress perception and flowering time.

PMID- 24587043
TI  - Myopia and digit ratio in medical college students.
AB  - Myopia is amongst the most common refractive errors in the world. Both
      environmental and genetic factors are attributed to its causation, however all
      factors contributing to the development of myopia is yet to be found. Recent
      studies show presence of sex hormone receptor in the eyes. This has been shown to
      have a role in the development of various ocular pathologies. The second to
      fourth finger length ratio (2D:4D) has been hypothesised to be determined by
      exposure to sex steroids prenatally and thus considered a crude measure for
      prenatal androgen exposure. Hence this study was initiated to assess the
      association between myopia and 2D:4D ratio (a proxy marker to prenatal sex
      steroid exposure) among 100 medical college students of either sex and explore
      the possibility of role of prenatal sex steroids in causation of myopia. This
      study showed significant negative associations between myopia and digit ratio
      favouring a probable causal role of sex steroids on eye growth and development of
      myopia. 

PMID- 24587044
TI  - Attracting STEM talent: do STEM students prefer traditional or work/life
      interaction labs?
AB  - The demand for employees trained in science, technology, engineering, and
      mathematics (STEM) fields continues to increase, yet the number of Millennial
      students pursuing STEM is not keeping pace. We evaluated whether this shortfall
      is associated with Millennials' preference for flexibility and work/life
      interaction in their careers-a preference that may be inconsistent with the
      traditional idea of a science career endorsed by many lab directors. Two
      contrasting approaches to running STEM labs and training students were explored,
      and we created a lab recruitment video depicting each. The work-focused video
      emphasized the traditional notions of a science lab, characterized by long work
      hours and a focus on individual achievement and conducting research above all
      else. In contrast, the work/life-interaction-focused video emphasized a more
      progressive view - lack of demarcation between work and non-work lives, flexible
      hours, and group achievement. In Study 1, 40 professors rated the videos, and the
      results confirmed that the two lab types reflected meaningful real-world
      differences in training approaches. In Study 2, we recruited 53 current and
      prospective graduate students in STEM fields who displayed high math
      identification and a commitment to science careers. In a between-subjects design,
      they watched one of the two lab-recruitment videos, and then reported their
      anticipated sense of belonging to and desire to participate in the lab depicted
      in the video. Very large effects were observed on both primary measures:
      Participants who watched the work/life-interaction-focused video reported a
      greater sense of belonging to (d = 1.49) and desire to participate in (d = 1.33)
      the lab, relative to participants who watched the work-focused video. These
      results suggest Millennials possess a strong desire for work/life-interaction,
      which runs counter to the traditional lab-training model endorsed by many lab
      directors. We discuss implications of these findings for STEM recruitment. 

PMID- 24587045
TI  - Hysteresis as an implicit prior in tactile spatial decision making.
AB  - Perceptual decisions not only depend on the incoming information from sensory
      systems but constitute a combination of current sensory evidence and internally
      accumulated information from past encounters. Although recent evidence emphasizes
      the fundamental role of prior knowledge for perceptual decision making, only few
      studies have quantified the relevance of such priors on perceptual decisions and
      examined their interplay with other decision-relevant factors, such as the
      stimulus properties. In the present study we asked whether hysteresis, describing
      the stability of a percept despite a change in stimulus property and known to
      occur at perceptual thresholds, also acts as a form of an implicit prior in
      tactile spatial decision making, supporting the stability of a decision across
      successively presented random stimuli (i.e., decision hysteresis). We applied a
      variant of the classical 2-point discrimination task and found that hysteresis
      influenced perceptual decision making: Participants were more likely to decide
      'same' rather than 'different' on successively presented pin distances. In a
      direct comparison between the influence of applied pin distances (explicit
      stimulus property) and hysteresis, we found that on average, stimulus property
      explained significantly more variance of participants' decisions than hysteresis.
      However, when focusing on pin distances at threshold, we found a trend for
      hysteresis to explain more variance. Furthermore, the less variance was explained
      by the pin distance on a given decision, the more variance was explained by
      hysteresis, and vice versa. Our findings suggest that hysteresis acts as an
      implicit prior in tactile spatial decision making that becomes increasingly
      important when explicit stimulus properties provide decreasing evidence. 

PMID- 24587046
TI  - Insight into highly conserved H1 subtype-specific epitopes in influenza virus
      hemagglutinin.
AB  - Influenza viruses continuously undergo antigenic changes with gradual
      accumulation of mutations in hemagglutinin (HA) that is a major determinant in
      subtype specificity. The identification of conserved epitopes within specific HA
      subtypes gives an important clue for developing new vaccines and diagnostics. We
      produced and characterized nine monoclonal antibodies that showed significant
      neutralizing activities against H1 subtype influenza viruses, and determined the
      complex structure of HA derived from a 2009 pandemic virus A/Korea/01/2009 (KR01)
      and the Fab fragment from H1-specific monoclonal antibody GC0587. The overall
      structure of the complex was essentially identical to the previously determined
      KR01 HA-Fab0757 complex structure. Both Fab0587 and Fab0757 recognize readily
      accessible head regions of HA, revealing broadly shared and conserved antigenic
      determinants among H1 subtypes. The beta-strands constituted by Ser110-Glu115 and
      Lys169-Lys170 form H1 epitopes with distinct conformations from those of H1 and
      H3 HA sites. In particular, Glu112, Glu115, Lys169, and Lys171 that are highly
      conserved among H1 subtype HAs have close contacts with HCDR3 and LCDR3. The
      differences between Fab0587 and Fab0757 complexes reside mainly in HCDR3 and
      LCDR3, providing distinct antigenic determinants specific for 1918 pdm influenza
      strain. Our results demonstrate a potential key neutralizing epitope important
      for H1 subtype specificity in influenza virus. 

PMID- 24587047
TI  - Features on MDCT that predict surgery in patients with adhesive-related small
      bowel obstruction.
AB  - PURPOSE: The purpose of this study was to determine the contribution of
      multidetector-row computed tomography (MDCT) in the management of adhesion
      related small bowel obstruction (SBO) and to identify its predictive value for
      surgery. METHODS: We conducted a retrospective review of 151 patients over a 5
      year period with the diagnosis of SBO caused by adhesion. These patients were
      divided into two groups: surgery (n =  63) and observation group (n =  88). Two
      radiologists blinded to the outcome of the patients evaluated MDCT images
      retrospectively, recording the bowel diameter, bowel wall thickness, degree of
      obstruction, air-fluid level, mesenteric fatty stranding, transitional zone,
      intraperitoneal fluid, close loop, whirl sign, and faeces sign. Statistical
      analyses were performed using univariate and multivariable analyses. RESULTS:
      Multivariable analysis showed that MDCT demonstrated presence of intraperitoneal
      fluid (Odds ratio, OR, 4.38), high-grade or complete obstruction (OR, 3.19) and
      mesenteric fatty stranding (OR, 2.81), and absence of faeces sign (OR, 2.11) were
      the most significant predictors. When all of the four criteria were used in
      combination, high sensitivity of 98.4% and specificity of 90.9% were achieved for
      the prediction for surgery. CONCLUSION: MDCT is useful to evaluate adhesion
      related SBO and to predict accurately patients who require surgery. Use of the
      four MDCT features in combination is highly suggestive of the need for early
      surgical intervention.

PMID- 24587048
TI  - Variations in lead isotopic abundances in Sprague-Dawley rat tissues: possible
      reason of formation.
AB  - It has been reported in previous research that the lead isotopic composition of
      blood, urine and feces samples statistically differed from the given lead sources
      in Sprague-Dawley (SD) rats. However, the reason for this phenomenon is still
      unclear. An animal experiment was performed to investigate the lead isotope
      fractionation in diverse biological samples (i.e., lungs, liver, kidneys, bone)
      and to explore the possible reasons. SD rats were intratracheally instilled with
      lead acetate at the concentrations of 0, 0.02, 0.2, and 2 mg/kg body weight.
      Biological samples were collected for lead isotope analysis using an inductively
      coupled plasma mass spectrometry (ICP-MS). Significant differences are observed
      in lead isotope abundances among the diverse biological samples. The lead isotope
      abundances ((206)Pb, (207)Pb and (208)Pb) in diverse biological samples show
      different degrees and directions of departure from the given lead source. The
      results suggest that differences in enrichment or depletion capacity for each
      lead isotope in the various tissues might lead to the variation in lead isotopic
      abundances in tissues. Moreover, a nonlinear relationship between the blood lead
      level and the lead isotope abundances in liver and bone is observed. When the
      whole-blood level is higher than 50 ng/mL, the lead isotopic compositions of
      biological samples tend to be the same. Thus, the data support the speculation of
      a fractionation functional threshold. 

PMID- 24587049
TI  - Short-term resveratrol exposure causes in vitro and in vivo growth inhibition and
      apoptosis of bladder cancer cells.
AB  - Conventional adjuvant chemotherapies for bladder transitional cell carcinomas
      (TCCs) may cause strong systemic toxicity and local irritation. Non-toxic
      resveratrol inhibits TCC cell growth but its feasibility in clinical management
      of TCCs remains obscure. This study aimed to evaluate the safety and anti-TCC
      efficacy of resveratrol, using the experimental models closer to the clinical
      treatment condition. Human TCC EJ cells were exposed to 100 uM, 150 uM and 200 uM
      resveratrol respectively for 1 hour and 2 hours to mimic intravesical drug
      instillation and the cell responses were analyzed by multiple experimental
      approaches. An orthotopic TCC nude mouse model was established by injecting EJ
      cells into the sub-urothelial layer and used for short-term intravesical
      resveratrol instillation. The safety of resveratrol instillation was evaluated
      and compared with that of MCC. The results revealed that 2 h 150 uM or 200 uM
      resveratrol treatment leaded to remarkable S phase arrest and apoptosis at 72 h
      time-point, accompanied with attenuated phosphorylation, nuclear translocation
      and transcription of STAT3, down-regulation of STAT3 downstream genes (survivin,
      cyclinD1, c-Myc and VEGF) and nuclear translocations of Sirt1 and p53. The
      importance of STAT3 signaling in cell growth was confirmed by treating EJ cells
      with JAK2 inhibitor tyrphostin AG490. The efficacy and safety of resveratrol
      instillation were proved by the findings from nude mouse orthotopic xenograft
      models, because this treatment caused growth suppression, distinctive apoptosis
      and STAT3 inactivation of the transplanted tumors without affecting normal
      urothelium. Our results thus suggest for the first time the practical values of
      resveratrol as a safe and effective agent in the post-operative treatment of
      TCCs. 

PMID- 24587050
TI  - An empirical assessment and comparison of species-based and habitat-based
      surrogates: a case study of forest vertebrates and large old trees.
AB  - A holy grail of conservation is to find simple but reliable measures of
      environmental change to guide management. For example, particular species or
      particular habitat attributes are often used as proxies for the abundance or
      diversity of a subset of other taxa. However, the efficacy of such kinds of
      species-based surrogates and habitat-based surrogates is rarely assessed, nor are
      different kinds of surrogates compared in terms of their relative effectiveness.
      We use 30-year datasets on arboreal marsupials and vegetation structure to
      quantify the effectiveness of: (1) the abundance of a particular species of
      arboreal marsupial as a species-based surrogate for other arboreal marsupial
      taxa, (2) hollow-bearing tree abundance as a habitat-based surrogate for arboreal
      marsupial abundance, and (3) a combination of species- and habitat-based
      surrogates. We also quantify the robustness of species-based and habitat-based
      surrogates over time. We then use the same approach to model overall species
      richness of arboreal marsupials. We show that a species-based surrogate can
      appear to be a valid surrogate until a habitat-based surrogate is co-examined,
      after which the effectiveness of the former is lost. The addition of a species
      based surrogate to a habitat-based surrogate made little difference in explaining
      arboreal marsupial abundance, but altered the co-occurrence relationship between
      species. Hence, there was limited value in simultaneously using a combination of
      kinds of surrogates. The habitat-based surrogate also generally performed
      significantly better and was easier and less costly to gather than the species
      based surrogate. We found that over 30 years of study, the relationships which
      underpinned the habitat-based surrogate generally remained positive but variable
      over time. Our work highlights why it is important to compare the effectiveness
      of different broad classes of surrogates and identify situations when either
      species- or habitat-based surrogates are likely to be superior. 

PMID- 24587051
TI  - Breeding experience, alternative reproductive strategies and reproductive success
      in a captive colony of zebra finches (Taeniopygia guttata).
AB  - Birds exhibit a remarkable diversity of different reproductive strategies both
      between and within species. Species such as the zebra finch (Taeniopygia guttata)
      may evolve the flexible use of alternative reproductive strategies, as well as
      benefit from prior breeding experience, which allows them to adaptively respond
      to unpredictable environments. In birds, the flexible use of alternative
      reproductive strategies, such as extra-pair mating, has been reported to be
      associated with fast reproduction, high mortality and environmental variability.
      However, little is known about the role of previous breeding experience in the
      adaptive use of alternative reproductive strategies. Here we performed an in
      depth study of reproductive outcomes in a population of domesticated zebra
      finches, testing the impact of prior breeding experience on the use of
      alternative reproductive strategies and reproductive success. We provide evidence
      that older females with prior breeding experience are quicker to initiate a
      clutch with a new partner and have increased success in chick rearing, even in a
      captive colony of zebra finches with minimal foraging demands. We also find
      evidence that the breeding experience of other females in the same social group
      influences reproductive investment by female zebra finches. Furthermore, we
      demonstrate that the use of alternative reproductive strategies in female zebra
      finches is associated with previous failed breeding attempts with the same pair
      partner. The results provide evidence that age and breeding experience play
      important roles in the flexible use of both facultative and adaptive reproductive
      strategies in female zebra finches. 

PMID- 24587052
TI  - CXCR4 inhibition ameliorates severe obliterative pulmonary hypertension and
      accumulation of C-kit+ cells in rats.
AB  - Successful curative treatment of severe pulmonary arterial hypertension with
      luminal obliteration will require a thorough understanding of the mechanism
      underlying the development and progression of pulmonary vascular lesions. But the
      cells that obliterate the pulmonary arterial lumen in severe pulmonary arterial
      hypertension are incompletely characterized. The goal of our study was to
      evaluate whether inhibition of CXC chemokine receptor 4 will prevent the
      accumulation of c-kit+ cells and severe pulmonary arterial hypertension. We
      detected c-kit+- cells expressing endothelial (von Willebrand Factor) or smooth
      muscle cell/myofibroblast (alpha-smooth muscle actin) markers in pulmonary
      arterial lesions of SU5416/chronic hypoxia rats. We found increased expression of
      CXC chemokine ligand 12 in the lung tissue of SU5416/chronic hypoxia rats. In our
      prevention study, AMD3100, an inhibitor of the CXC chemokine ligand 12 receptor,
      CXC chemokine receptor 4, only moderately decreased pulmonary arterial
      obliteration and pulmonary hypertension in SU5416/chronic hypoxia animals.
      AMD3100 treatment reduced the number of proliferating c-kit+ alpha-smooth muscle
      actin+ cells and pulmonary arterial muscularization and did not affect c-kit+ von
      Willebrand Factor+ cell numbers. Both c-kit+ cell types expressed CXC chemokine
      receptor 4. In conclusion, our data demonstrate that in the SU5416/chronic
      hypoxia model of severe pulmonary hypertension, the CXC chemokine receptor 4
      expressing c-kit+ alpha-smooth muscle actin+ cells contribute to pulmonary
      arterial muscularization. In contrast, vascular lumen obliteration by c-kit+ von
      Willebrand Factor+ cells is largely independent of CXC chemokine receptor 4.

PMID- 24587053
TI  - 2, 3, 7, 8-Tetrachlorodibenzo-P-dioxin (TCDD) induces premature senescence in
      human and rodent neuronal cells via ROS-dependent mechanisms.
AB  - The widespread environmental pollutant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)
      is a potent toxicant that causes significant neurotoxicity. However, the
      biological events that participate in this process remain largely elusive. In the
      present study, we demonstrated that TCDD exposure triggered apparent premature
      senescence in rat pheochromocytoma (PC12) and human neuroblastoma SH-SY5Y cells.
      Senescence-associated beta-galactosidase (SA-beta-Gal) assay revealed that TCDD
      induced senescence in PC12 neuronal cells at doses as low as 10 nM. TCDD led to F
      actin reorganization and the appearance of an alternative senescence marker,
      gamma-H2AX foci, both of which are important features of cellular senescence. In
      addition, TCDD exposure altered the expression of senescence marker proteins,
      such as p16, p21 and p-Rb, in both dose- and time-dependent manners. Furthermore,
      we demonstrated that TCDD promotes mitochondrial dysfunction and the accumulation
      of cellular reactive oxygen species (ROS) in PC12 cells, leading to the
      activation of signaling pathways that are involved in ROS metabolism and
      senescence. TCDD-induced ROS generation promoted significant oxidative DNA damage
      and lipid peroxidation. Notably, treatment with the ROS scavenger N
      acetylcysteine (NAC) markedly attenuated TCDD-induced ROS production, cellular
      oxidative damage and neuronal senescence. Moreover, we found that TCDD induced a
      similar ROS-mediated senescence response in human neuroblastoma SH-SY5Y cells. In
      sum, these results demonstrate for the first time that TCDD induces premature
      senescence in neuronal cells by promoting intracellular ROS production,
      supporting the idea that accelerating the onset of neuronal senescence may be an
      important mechanism underlying TCDD-induced neurotoxic effects. 

PMID- 24587054
TI  - Attention deficit associated with early life interictal spikes in a rat model is
      improved with ACTH.
AB  - Children with epilepsy often present with pervasive cognitive and behavioral
      comorbidities including working memory impairments, attention deficit
      hyperactivity disorder (ADHD) and autism spectrum disorder. These non-seizure
      characteristics are severely detrimental to overall quality of life. Some of
      these children, particularly those with epilepsies classified as Landau-Kleffner
      Syndrome or continuous spike and wave during sleep, have infrequent seizure
      activity but frequent focal epileptiform activity. This frequent epileptiform
      activity is thought to be detrimental to cognitive development; however, it is
      also possible that these IIS events initiate pathophysiological pathways in the
      developing brain that may be independently associated with cognitive deficits.
      These hypotheses are difficult to address due to the previous lack of an
      appropriate animal model. To this end, we have recently developed a rat model to
      test the role of frequent focal epileptiform activity in the prefrontal cortex.
      Using microinjections of a GABA(A) antagonist (bicuculline methiodine) delivered
      multiple times per day from postnatal day (p) 21 to p25, we showed that rat pups
      experiencing frequent, focal, recurrent epileptiform activity in the form of
      interictal spikes during neurodevelopment have significant long-term deficits in
      attention and sociability that persist into adulthood. To determine if treatment
      with ACTH, a drug widely used to treat early-life seizures, altered outcome we
      administered ACTH once per day subcutaneously during the time of the induced
      interictal spike activity. We show a modest amelioration of the attention deficit
      seen in animals with a history of early life interictal spikes with ACTH, in the
      absence of alteration of interictal spike activity. These results suggest that
      pharmacological intervention that is not targeted to the interictal spike
      activity is worthy of future study as it may be beneficial for preventing or
      ameliorating adverse cognitive outcomes.

PMID- 24587055
TI  - Identification of a fungi-specific lineage of protein kinases closely related to
      tyrosine kinases.
AB  - Tyrosine kinases (TKs) specifically catalyze the phosphorylation of tyrosine
      residues in proteins and play essential roles in many cellular processes.
      Although TKs mainly exist in animals, recent studies revealed that some organisms
      outside the Opisthokont clade also contain TKs. The fungi, as the sister group to
      animals, are thought to lack TKs. To better understand the origin and evolution
      of TKs, it is important to investigate if fungi have TK or TK-related genes. We
      therefore systematically identified possible TKs across the fungal kingdom by
      using the profile hidden Markov Models searches and phylogenetic analyses. Our
      results confirmed that fungi lack the orthologs of animal TKs. We identified a
      fungi-specific lineage of protein kinases (FslK) that appears to be a sister
      group closely related to TKs. Sequence analysis revealed that members of the FslK
      clade contain all the conserved protein kinase sub-domains and thus are likely
      enzymatically active. However, they lack key amino acid residues that determine
      TK-specific activities, indicating that they are not true TKs. Phylogenetic
      analysis indicated that the last common ancestor of fungi may have possessed
      numerous members of FslK. The ancestral FslK genes were lost in Ascomycota and
      Ustilaginomycotina and Pucciniomycotina of Basidiomycota during evolution. Most
      of these ancestral genes, however, were retained and expanded in Agaricomycetes.
      The discovery of the fungi-specific lineage of protein kinases closely related to
      TKs helps shed light on the origin and evolution of TKs and also has potential
      implications for the importance of these kinases in mushroom fungi. 

PMID- 24587056
TI  - Evaluation of in-hospital management for febrile illness in Northern Tanzania
      before and after 2010 World Health Organization Guidelines for the treatment of
      malaria.
AB  - OBJECTIVE: In 2010, the World Health Organization (WHO) published updated
      guidelines emphasizing and expanding recommendations for a parasitological
      confirmation of malaria before treating with antimalarials. This study aimed to
      assess differences in historic (2007-2008) (cohort 1) and recent (2011-2012)
      (cohort 2) hospital cohorts in the diagnosis and treatment of febrile illness in
      a low malaria prevalence area of northern Tanzania. MATERIALS AND METHODS: We
      analyzed data from two prospective cohort studies that enrolled febrile
      adolescents and adults aged >=13 years. All patients received quality-controlled
      aerobic blood cultures and malaria smears. We compared patients' discharge
      diagnoses, treatments, and outcomes to assess changes in the treatment of malaria
      and bacterial infections. RESULTS: In total, 595 febrile inpatients were enrolled
      from two referral hospitals in Moshi, Tanzania. Laboratory-confirmed malaria was
      detected in 13 (3.2%) of 402 patients in cohort 1 and 1 (0.5%) of 193 patients in
      cohort 2 (p = 0.041). Antimalarials were prescribed to 201 (51.7%) of 389 smear
      negative patients in cohort 1 and 97 (50.5%) of 192 smear-negative patients in
      cohort 2 (p = 0.794). Bacteremia was diagnosed from standard blood culture in 58
      (14.5%) of 401 patients in cohort 1 compared to 18 (9.5%) of 190 patients in
      cohort 2 (p = 0.091). In cohort 1, 40 (69.0%) of 58 patients with a positive
      blood culture received antibacterials compared to 16 (88.9%) of 18 patients in
      cohort 2 (p = 0.094). In cohort 1, 43 (10.8%) of the 399 patients with known
      outcomes died during hospitalization compared with 12 (6.2%) deaths among 193
      patients in cohort 2 (p = 0.073). DISCUSSION: In a setting of low malaria
      transmission, a high proportion of smear-negative patients were diagnosed with
      malaria and treated with antimalarials despite updated WHO guidelines on malaria
      treatment. Improved laboratory diagnostics for non-malaria febrile illness might
      help to curb this practice.

PMID- 24587057
TI  - Stability indicators in network reconstruction.
AB  - The number of available algorithms to infer a biological network from a dataset
      of high-throughput measurements is overwhelming and keeps growing. However,
      evaluating their performance is unfeasible unless a 'gold standard' is available
      to measure how close the reconstructed network is to the ground truth. One
      measure of this is the stability of these predictions to data resampling
      approaches. We introduce NetSI, a family of Network Stability Indicators, to
      assess quantitatively the stability of a reconstructed network in terms of
      inference variability due to data subsampling. In order to evaluate network
      stability, the main NetSI methods use a global/local network metric in
      combination with a resampling (bootstrap or cross-validation) procedure. In
      addition, we provide two normalized variability scores over data resampling to
      measure edge weight stability and node degree stability, and then introduce a
      stability ranking for edges and nodes. A complete implementation of the NetSI
      indicators, including the Hamming-Ipsen-Mikhailov (HIM) network distance adopted
      in this paper is available with the R package nettools. We demonstrate the use of
      the NetSI family by measuring network stability on four datasets against
      alternative network reconstruction methods. First, the effect of sample size on
      stability of inferred networks is studied in a gold standard framework on yeast
      like data from the Gene Net Weaver simulator. We also consider the impact of
      varying modularity on a set of structurally different networks (50 nodes, from 2
      to 10 modules), and then of complex feature covariance structure, showing the
      different behaviours of standard reconstruction methods based on Pearson
      correlation, Maximum Information Coefficient (MIC) and False Discovery Rate (FDR)
      strategy. Finally, we demonstrate a strong combined effect of different
      reconstruction methods and phenotype subgroups on a hepatocellular carcinoma
      miRNA microarray dataset (240 subjects), and we validate the analysis on a second
      dataset (166 subjects) with good reproducibility. 

PMID- 24587058
TI  - Analysis of differential gene expression and novel transcript units of ovine
      muscle transcriptomes.
AB  - In this study, we characterized differentially expressed genes (DEGs) between the
      muscle transcriptomes of Small-tailed Han sheep and Dorper sheep and predicted
      novel transcript units using high-throughput RNA sequencing technology. Gene
      Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses showed
      that 1,300 DEGs were involved in cellular processes, metabolic pathways, and the
      actin cytoskeleton pathway. Importantly, we identified 34 DEGs related to muscle
      cell development and differentiation. Additionally, we were able to optimize the
      gene structure and predict the untranslated regions (UTRs) for some of the DEGs.
      Among the 123,678 novel predicted transcript units (TUs), 15,015 units were
      predicted protein sequences. The reliability of the sequencing data was verified
      through qRT-PCR analysis of 12 genes. These results will provide useful
      information for functional genetic research in the future. 

PMID- 24587060
TI  - Genistein partly eases aging and estropause-induced primary cortical neuronal
      changes in rats.
AB  - Gonadal hormones can modulate brain morphology and behavior. Recent studies have
      shown that hypogonadism could result in cortical function deficits. To this end,
      hormone therapy has been used to ease associated symptoms but the risk may
      outweigh the benefits. Here we explored whether genistein, a phytoestrogen, is
      effective in restoring the cognitive and central neuronal changes in late middle
      age and surgically estropause female rats. Both animal groups showed poorer
      spatial learning than young adults. The dendritic arbors and spines of the
      somatosensory cortical and CA1 hippocampal pyramidal neurons were revealed with
      intracellular dye injection and analyzed. The results showed that dendritic
      spines on these neurons were significantly decreased. Remarkably, genistein
      treatment rescued spatial learning deficits and restored the spine density on all
      neurons in the surgically estropause young females. In late middle age females,
      genistein was as effective as estradiol in restoring spines; however, the
      recovery was less thorough than on young OHE rats. Neither genistein nor
      estradiol rectified the shortened dendritic arbors of the aging cortical
      pyramidal neurons suggesting that dendritic arbors and spines are differently
      modulated. Thus, genistein could work at central level to restore excitatory
      connectivity and appears to be potent alternative to estradiol for easing aging
      and menopausal syndromes. 

PMID- 24587059
TI  - Development and assessment of plant-based synthetic odor baits for surveillance
      and control of malaria vectors.
AB  - BACKGROUND: Recent malaria vector control measures have considerably reduced
      indoor biting mosquito populations. However, reducing the outdoor biting
      populations remains a challenge because of the unavailability of appropriate
      lures to achieve this. This study sought to test the efficacy of plant-based
      synthetic odor baits in trapping outdoor populations of malaria vectors.
      METHODOLOGY AND PRINCIPAL FINDING: Three plant-based lures ((E)-linalool oxide
      [LO], (E)-linalool oxide and (E)-beta-ocimene [LO + OC], and a six-component
      blend comprising (E)-linalool oxide, (E)-beta-ocimene, hexanal, beta-pinene,
      limonene, and (E)-beta-farnesene [Blend C]), were tested alongside an
      animal/human-based synthetic lure (comprising heptanal, octanal, nonanal, and
      decanal [Blend F]) and worn socks in a malaria endemic zone in the western part
      of Kenya. Mosquito Magnet-X (MM-X) and lightless Centre for Disease Control (CDC)
      light traps were used. Odor-baited traps were compared with traps baited with
      either solvent alone or solvent + carbon dioxide (controls) for 18 days in a
      series of randomized incomplete-block designs of days * sites * treatments. The
      interactive effect of plant and animal/human odor was also tested by combining LO
      with either Blend F or worn socks. Our results show that irrespective of trap
      type, traps baited with synthetic plant odors compared favorably to the same
      traps baited with synthetic animal odors and worn socks in trapping malaria
      vectors, relative to the controls. Combining LO and worn socks enhanced trap
      captures of Anopheles species while LO + Blend F recorded reduced trap capture.
      Carbon dioxide enhanced total trap capture of both plant- and animal/human
      derived odors. However, significantly higher proportions of male and engorged
      female Anopheles gambiae s.l. were caught when the odor treatments did not
      include carbon dioxide. CONCLUSION AND SIGNIFICANCE: The results highlight the
      potential of plant-based odors and specifically linalool oxide, with or without
      carbon dioxide, for surveillance and mass trapping of malaria vectors.

PMID- 24587061
TI  - Striking discrepancy of anomalous body experiences with normal interoceptive
      accuracy in depersonalization-derealization disorder.
AB  - BACKGROUND: Disembodiment is a core feature of depersonalization disorder (DPD).
      Given the narratives of DPD patients about their disembodiment and emotional
      numbing and neurobiological findings of an inhibition of insular activity, DPD
      may be considered as a mental disorder with specific impairments of interoceptive
      awareness and body perception. METHODS: We investigated cardioceptive accuracy
      (CA) of DPD patients (n=24) as compared to healthy controls (n=26) with two
      different heartbeat detection tasks ("Schandry heartbeat counting task" and
      "Whitehead heartbeat discrimination task"). Self-rated clearness of body
      perception was measured by questionnaire. RESULTS: Contrary to our hypothesis,
      DPD patients performed similarly to healthy controls on the two different
      heartbeat detection tasks, and they had equal scores regarding their self-rated
      clearness of body perception. There was no correlation of the severity of
      "anomalous body experiences" and depersonalization with measures of interoceptive
      accuracy. Only among healthy controls CA in the Schandry task was positively
      correlated with self-rated clearness of body perception. Depersonalization was
      unrelated to severity of depression or anxiety, while depression and anxiety were
      highly correlated. Anxiety and depression did not modify the associations of
      depersonalization with interoceptive accuracy. CONCLUSIONS: Our main findings
      highlight a striking discrepancy of normal interoception with overwhelming
      experiences of disembodiment in DPD. This may reflect difficulties of DPD
      patients to integrate their visceral and bodily perceptions into a sense of their
      selves. This problem may be considered an important target for psychotherapeutic
      treatment approaches.

PMID- 24587062
TI  - Syndecan-1 regulates vascular smooth muscle cell phenotype.
AB  - OBJECTIVE: We examined the role of syndecan-1 in modulating the phenotype of
      vascular smooth muscle cells in the context of endogenous inflammatory factors
      and altered microenvironments that occur in disease or injury-induced vascular
      remodeling. METHODS AND RESULTS: Vascular smooth muscle cells (vSMCs) display a
      continuum of phenotypes that can be altered during vascular remodeling. While the
      syndecans have emerged as powerful and complex regulators of cell function, their
      role in controlling vSMC phenotype is unknown. Here, we isolated vSMCs from wild
      type (WT) and syndecan-1 knockout (S1KO) mice. Gene expression and western
      blotting studies indicated decreased levels of alpha-smooth muscle actin (alpha
      SMA), calponin, and other vSMC-specific differentiation markers in S1KO relative
      to WT cells. The spread area of the S1KO cells was found to be greater than WT
      cells, with a corresponding increase in focal adhesion formation, Src
      phosphorylation, and alterations in actin cytoskeletal arrangement. In addition,
      S1KO led to increased S6RP phosphorylation and decreased AKT and PKC-alpha
      phosphorylation. To examine whether these changes were present in vivo, isolated
      aortae from aged WT and S1KO mice were stained for calponin. Consistent with our
      in-vitro findings, the WT mice aortae stained higher for calponin relative to
      S1KO. When exposed to the inflammatory cytokine TNF-alpha, WT vSMCs had an 80%
      reduction in syndecan-1 expression. Further, with TNF-alpha, S1KO vSMCs produced
      increased pro-inflammatory cytokines relative to WT. Finally, inhibition of
      interactions between syndecan-1 and integrins alphavbeta3 and alphavbeta5 using
      the inhibitory peptide synstatin appeared to have similar effects on vSMCs as
      knocking out syndecan-1, with decreased expression of vSMC differentiation
      markers and increased expression of inflammatory cytokines, receptors, and
      osteopontin. CONCLUSIONS: Taken together, our results support that syndecan-1
      promotes vSMC differentiation and quiescence. Thus, the presence of syndecan-1
      would have a protective effect against vSMC dedifferentiation and this activity
      is linked to interactions with integrins alphavbeta3 and alphavbeta5.

PMID- 24587063
TI  - Model-observer similarity, error modeling and social learning in rhesus macaques.
AB  - Monkeys readily learn to discriminate between rewarded and unrewarded items or
      actions by observing their conspecifics. However, they do not systematically
      learn from humans. Understanding what makes human-to-monkey transmission of
      knowledge work or fail could help identify mediators and moderators of social
      learning that operate regardless of language or culture, and transcend inter
      species differences. Do monkeys fail to learn when human models show a behavior
      too dissimilar from the animals' own, or when they show a faultless performance
      devoid of error? To address this question, six rhesus macaques trained to find
      which object within a pair concealed a food reward were successively tested with
      three models: a familiar conspecific, a 'stimulus-enhancing' human actively
      drawing the animal's attention to one object of the pair without actually
      performing the task, and a 'monkey-like' human performing the task in the same
      way as the monkey model did. Reward was manipulated to ensure that all models
      showed equal proportions of errors and successes. The 'monkey-like' human model
      improved the animals' subsequent object discrimination learning as much as a
      conspecific did, whereas the 'stimulus-enhancing' human model tended on the
      contrary to retard learning. Modeling errors rather than successes optimized
      learning from the monkey and 'monkey-like' models, while exacerbating the adverse
      effect of the 'stimulus-enhancing' model. These findings identify error modeling
      as a moderator of social learning in monkeys that amplifies the models'
      influence, whether beneficial or detrimental. By contrast, model-observer
      similarity in behavior emerged as a mediator of social learning, that is, a
      prerequisite for a model to work in the first place. The latter finding suggests
      that, as preverbal infants, macaques need to perceive the model as 'like-me' and
      that, once this condition is fulfilled, any agent can become an effective model. 

PMID- 24587064
TI  - Altered lipid levels in untreated patients with early polymyositis.
AB  - BACKGROUND: Little is known so far on the lipid profile in polymyositis (PM)
      patients. Our aim is to identify lipid profiles in untreated patients with early
      PM, to assess the association between lipid profiles and C-reactive protein (a
      sensitive marker of inflammation) in these patients. METHODS AND FINDINGS: This
      work was conducted as a case-control study. Sixty untreated patients with PM and
      60 age- and sex-matched healthy controls were included. The duration of PM was
      less than six months, and none of them had received intermittent or regular
      corticosteroids or disease-modifying antirheumatic drugs or biological agents
      prior to the study. Triglyceride (TG), total cholesterol (TC), LDL-cholesterol
      (LDL-C), and HDL-cholesterol (HDL-C), and C-reactive protein (CRP) were assessed
      using standard techniques. Thirty patients (50%) had a decreased level of HDL-C
      and 47% had an increased level of TG. The levels of HDL-C, LDL-C, and TC in PM
      were significantly lower than in controls (P<0.001, P<0.01, P<0.001,
      respectively). The level of TG was significantly higher in PM than in controls
      (P<0.001). The level of very low LDL-cholesterol (VLDL-C), and the ratios of VLDL
      C/LDL-C, TC/HDL-C, and LDL-C/HDL-C were significantly higher than in controls
      (all P<0.001). Serum CRP levels correlated negatively with HDL-C (r = -0.352, P =
      0.006) and TC (r = -0.262, P = 0.043). After adjustment for age, gender, smoking,
      drinking, body mass index, and pulmonary fibrosis/infection, linear regression
      model demonstrated that CRP is associated with HDL-C among PM patients (P =
      0.028). CONCLUSIONS: Dyslipidemia is a common feature in patients with PM that is
      characterized by a decrease in HDL-C and an increase in TG, suggesting a high
      risk of atherosclerosis. The Inflammatory condition in PM may account for the
      metabolism of HDL-C.

PMID- 24587066
TI  - Adverse drug reactions of spontaneous reports in Shanghai pediatric population.
AB  - BACKGROUND: Knowledge of drug safety in the pediatric population of China is
      limited. This study was designed to evaluate ADRs in children reported to the
      spontaneous reporting system (SRS) of Shanghai in 2009. METHODOLOGY AND PRINCIPAL
      FINDINGS: Crude ADR reports submitted to Shanghai SRS in 2009 for individuals
      aged from birth to 17 years (including 17 years) were included. Data were
      analyzed with respect to age, gender, category of ADR (System Organ Class [SOC]),
      the severity of reports and type of reporter. RESULTS: A male overrepresentation
      was observed regarding the total number of reports. The most frequently reported
      group of drugs were vaccines (42.15%). Skin rash and fever were the commonest
      symptoms reported in the total pediatric dataset. The proportion of children that
      suffered from a serious ADR was 2.16% and that for drug related deaths was 0.34%.
      And we found that the multiple drug exposure experienced a high proportion of
      serious ADRs compared with the single drug use (chi2 = 15.99, P<0.0001). Sixty
      five percent of ADRs were for children less than 6 years of age. And more than
      half of reports were from doctors. CONCLUSIONS: In our study, consumers were more
      likely to report new ADRs though they appear to contribute a relatively small
      percentage of total reports. We propose that patients would take an active role
      in reporting ADRs. More researches are needed in order to achieve better
      understanding the characteristics of ADRs in pediatric population of China.

PMID- 24587065
TI  - Telomere length as a biomarker for adiposity changes after a multidisciplinary
      intervention in overweight/obese adolescents: the EVASYON study.
AB  - CONTEXT: Telomeres are biomarkers of biological aging. Shorter telomeres have
      been associated with increased adiposity in adults. However, this relationship
      remains unclear in children and adolescents. OBJECTIVE: To evaluate the
      association between telomere length (TL) and adiposity markers in
      overweight/obese adolescents after an intensive program. We hypothesize that
      greater TL at baseline would predict a better response to a weight loss
      treatment. DESIGN SETTING PATIENTS AND INTERVENTION: The EVASYON is a
      multidisciplinary treatment program for adolescents with overweight and obesity
      that is aimed at applying the intervention to all possibly involved areas of the
      individual, such as dietary habits, physical activity and cognitive and
      psychological profiles. Seventy-four participants (36 males, 38 females, 12-16
      yr) were enrolled in the intervention program: 2 months of an energy-restricted
      diet and a follow-up period (6 months). MAIN OUTCOME: TL was measured by
      quantitative real-time polymerase chain reaction at baseline and after 2 months;
      meanwhile, anthropometric variables were also assessed after 6 months of follow
      up. RESULTS: TL lengthened in participants during the intensive period (+1.9+/
      1.0, p<0.001) being greater in overweight/obese adolescents with the shortest
      telomeres at baseline (r = -0.962, p<0.001). Multivariable linear regression
      analysis showed that higher baseline TL significantly predicted a higher decrease
      in body weight (B = -1.53, p = 0.005; B = -2.25, p = 0.047) and in standard
      deviation score for body mass index (BMI-SDS) (B = -0.22, p = 0.010; B = -0.47, p
      = 0.005) after the intensive and extensive period treatment respectively, in
      boys. CONCLUSION: Our study shows that a weight loss intervention is accompanied
      by a significant increase in TL in overweight/obese adolescents. Moreover, we
      suggest that initial longer TL could be a potential predictor for a better weight
      loss response.

PMID- 24587067
TI  - Clonogenicity: holoclones and meroclones contain stem cells.
AB  - When primary cultures of normal cells are cloned, three types of colony grow,
      called holoclones, meroclones and paraclones. These colonies are believed to be
      derived from stem cells, transit-amplifying cells and differentiated cells
      respectively. More recently, this approach has been extended to cancer cell
      lines. However, we observed that meroclones from the prostate cancer cell line
      DU145 produce holoclones, a paradoxical observation as meroclones are thought to
      be derived from transit-amplifying cells. The purpose of this study was to
      confirm this observation and determine if both holoclones and meroclones from
      cancer cell lines contain stem cells. We demonstrated that both holoclones and
      meroclones can be serially passaged indefinitely, are highly proliferative, can
      self-renew to form spheres, are serially tumorigenic and express stem cell
      markers. This study demonstrates that the major difference between holoclones and
      meroclones derived from a cancer cell line is the proportion of stem cells within
      each colony, not the presence or absence of stem cells. These findings may
      reflect the properties of cancer as opposed to normal cells, perhaps indicating
      that the hierarchy of stem cells is more extensive in cancer. 

PMID- 24587068
TI  - A psycho-educational HIV/STI prevention intervention for internally displaced
      women in Leogane, Haiti: results from a non-randomized cohort pilot study.
AB  - BACKGROUND: Little evidence exists regarding efficacious HIV and sexually
      transmitted infections (STI) prevention interventions with internally displaced
      populations. Internally displaced women are at elevated risk for HIV/STI due to
      limited access to health services, heightened poverty and social network
      breakdown. The FASY (Famn an Aksyon Pou Sante' Yo) (Women Taking Action For Their
      Health) study examined the effectiveness of a peer health worker (PHW) delivered
      psycho-educational HIV/STI pilot study with internally displaced women in
      Leogane, Haiti. METHOD: This was a non-randomized cohort pilot study.
      Participants completed a computer-assisted pre-test programmed on Android tablet
      PCs followed by an HIV/STI educational video-based session and a 6-week psycho
      educational group program of weekly meetings. Participants completed a post-test
      upon completion of group sessions. The primary outcome was HIV knowledge; our pre
      specified index of clinically significant change was an effect size of 0.30.
      Secondary outcomes included: STI knowledge, condom use, social support, resilient
      coping, depression and relationship control. We used mixed-effects regression to
      calculate mean outcome pre-post score change. This study was registered
      (clinicaltrials.gov, NCT01492829). RESULTS: Between January 1-April 30, 2012 we
      assigned 200 participants to the study. The majority of participants (n = 176,
      88%) completed the study and were followed up at 8 weeks, finishing April 30,
      2012. Adjusted for socio-demographic characteristics, HIV knowledge (beta = 4.81;
      95% CI 4.36-5.26), STI knowledge (beta = 0.84; 95% CI 0.70-0.99), condom use (AOR
      = 4.05, 95% CI 1.86-8.83), and depression (beta = -0.63, 95% CI -0.88--0.39)
      scores showed statistically significant change post-intervention (p<0.05).
      CONCLUSIONS: This pilot study evaluated a PHW psycho-educational HIV/STI
      prevention intervention among internally displaced women in post-earthquake
      Haiti. Pilot studies are an important approach to understand feasibility and
      scientific impacts of HIV prevention strategies in disaster contexts. Study
      results may inform HIV prevention interventions among internally displaced women
      in Haiti and can be tested for applicability with internally displaced women
      globally. ClinicalTrials.gov: Identifier NCT01492829, URL:
      http://clinicaltrials.gov/ct2/show/NCT01492829?term=logie&rank=1.

PMID- 24587069
TI  - Macro-invertebrate decline in surface water polluted with imidacloprid: a
      rebuttal and some new analyses.
AB  - Imidacloprid, the largest selling insecticide in the world, has received
      particular attention from scientists, policymakers and industries due to its
      potential toxicity to bees and aquatic organisms. The decline of aquatic macro
      invertebrates due to imidacloprid concentrations in the Dutch surface waters was
      hypothesised in a recent paper by Van Dijk, Van Staalduinen and Van der Sluijs
      (PLOS ONE, May 2013). Although we do not disagree with imidacloprid's inherent
      toxicity to aquatic organisms, we have fundamental concerns regarding the way the
      data were analysed and interpreted. Here, we demonstrate that the underlying
      toxicity of imidacloprid in the field situation cannot be understood except in
      the context of other co-occurring pesticides. Although we agree with Van Dijk and
      co-workers that effects of imidacloprid can emerge between 13 and 67 ng/L we use
      a different line of evidence. We present an alternative approach to link
      imidacloprid concentrations and biological data. We analysed the national set of
      chemical monitoring data of the year 2009 to estimate the relative contribution
      of imidacloprid compared to other pesticides in relation to environmental quality
      target and chronic ecotoxicity threshold exceedances. Moreover, we assessed the
      relative impact of imidacloprid on the pesticide-induced potential affected
      fractions of the aquatic communities. We conclude that by choosing to test a
      starting hypothesis using insufficient data on chemistry and biology that are
      difficult to link, and by ignoring potential collinear effects of other
      pesticides present in Dutch surface waters Van Dijk and co-workers do not provide
      direct evidence that reduced taxon richness and abundance of macroinvertebrates
      can be attributed to the presence of imidacloprid only. Using a different line of
      evidence we expect ecological effects of imidacloprid at some of the exposure
      profiles measured in 2009 in the surface waters of the Netherlands. 

PMID- 24587071
TI  - Consumption of lean fish reduces the risk of type 2 diabetes mellitus: a
      prospective population based cohort study of Norwegian women.
AB  - BACKGROUND: The effects of fish consumption and n-3 fatty acids on type 2
      diabetes mellitus (T2DM) have recently been debated. OBJECTIVE: We explored the
      risk of T2DM in relation to consumption of lean fish, fatty fish, fish products
      and total fish as well as cod liver oil supplements in a representative sample of
      Norwegian women. DESIGN: This was a prospective population based cohort study in
      33740 women free of T2DM, stroke, angina or heart attack and with detailed
      information on important co-variates and dietary intake at baseline. Risk ratios
      and corresponding 95% CI were estimated using Poisson regression with log-person
      time as offset. RESULTS: Lean fish consumption was inversely associated with T2DM
      compared to zero intake. Risk ratios and 95% CI for intake of 75 and 100 g lean
      fish per day were 0.71 (0.51, 0.98) and 0.67 (0.46, 0.98), respectively. There
      was no effect of intake of fatty fish, fish products, total fish or use of cod
      liver oil supplements on the risk of T2DM. CONCLUSION: Lean fish consumption of
      75-100 g/d had a beneficial effect on T2DM. It remains unclear whether lean fish
      in itself has a protective effect on T2DM or that lean fish consumers have a
      protective life-style that we were not able to take into account in this study.
      Unfavorable effects of fatty fish consumption or use of cod liver oil supplements
      on T2DM were not observed.

PMID- 24587070
TI  - Negative mood state enhances the susceptibility to unpleasant events: neural
      correlates from a music-primed emotion classification task.
AB  - BACKGROUND: Various affective disorders are linked with enhanced processing of
      unpleasant stimuli. However, this link is likely a result of the dominant
      negative mood derived from the disorder, rather than a result of the disorder
      itself. Additionally, little is currently known about the influence of mood on
      the susceptibility to emotional events in healthy populations. METHOD: Event
      Related Potentials (ERP) were recorded for pleasant, neutral and unpleasant
      pictures while subjects performed an emotional/neutral picture classification
      task during positive, neutral, or negative mood induced by instrumental Chinese
      music. RESULTS: Late Positive Potential (LPP) amplitudes were positively related
      to the affective arousal of pictures. The emotional responding to unpleasant
      pictures, indicated by the unpleasant-neutral differences in LPPs, was enhanced
      during negative compared to neutral and positive moods in the entire LPP time
      window (600-1000 ms). The magnitude of this enhancement was larger with
      increasing self-reported negative mood. In contrast, this responding was reduced
      during positive compared to neutral mood in the 800-1000 ms interval.
      Additionally, LPP reactions to pleasant stimuli were similar across positive,
      neutral and negative moods except those in the 800-900 ms interval. IMPLICATIONS:
      Negative mood intensifies the humans' susceptibility to unpleasant events in
      healthy individuals. In contrast, music-induced happy mood is effective in
      reducing the susceptibility to these events. Practical implications of these
      findings were discussed.

PMID- 24587072
TI  - Increased actin polymerization and stabilization interferes with neuronal
      function and survival in the AMPKgamma mutant Loechrig.
AB  - loechrig (loe) mutant flies are characterized by progressive neuronal
      degeneration, behavioral deficits, and early death. The mutation is due to a P
      element insertion in the gene for the gamma-subunit of the trimeric AMP-activated
      protein kinase (AMPK) complex, whereby the insertion affects only one of several
      alternative transcripts encoding a unique neuronal isoform. AMPK is a cellular
      energy sensor that regulates a plethora of signaling pathways, including
      cholesterol and isoprenoid synthesis via its downstream target hydroxy
      methylglutaryl (HMG)-CoA reductase. We recently showed that loe interferes with
      isoprenoid synthesis and increases the prenylation and thereby activation of
      RhoA. During development, RhoA plays an important role in neuronal outgrowth by
      activating a signaling cascade that regulates actin dynamics. Here we show that
      the effect of loe/AMPKgamma on RhoA prenylation leads to a hyperactivation of
      this signaling pathway, causing increased phosphorylation of the actin
      depolymerizating factor cofilin and accumulation of filamentous actin.
      Furthermore, our results show that the resulting cytoskeletal changes in loe
      interfere with neuronal growth and disrupt axonal integrity. Surprisingly, these
      phenotypes were enhanced by expressing the Slingshot (SSH) phosphatase, which
      during development promotes actin depolymerization by dephosphorylating cofilin.
      However, our studies suggest that in the adult SSH promotes actin polymerization,
      supporting in vitro studies using human SSH1 that suggested that SSH can also
      stabilize and bundle filamentous actin. Together with the observed increase in
      SSH levels in the loe mutant, our experiments suggest that in mature neurons SSH
      may function as a stabilization factor for filamentous actin instead of promoting
      actin depolymerization. 

PMID- 24587073
TI  - Selective REM-sleep deprivation does not diminish emotional memory consolidation
      in young healthy subjects.
AB  - Sleep enhances memory consolidation and it has been hypothesized that rapid eye
      movement (REM) sleep in particular facilitates the consolidation of emotional
      memory. The aim of this study was to investigate this hypothesis using selective
      REM-sleep deprivation. We used a recognition memory task in which participants
      were shown negative and neutral pictures. Participants (N=29 healthy medical
      students) were separated into two groups (undisturbed sleep and selective REM
      sleep deprived). Both groups also worked on the memory task in a wake condition.
      Recognition accuracy was significantly better for negative than for neutral
      stimuli and better after the sleep than the wake condition. There was, however,
      no difference in the recognition accuracy (neutral and emotional) between the
      groups. In summary, our data suggest that REM-sleep deprivation was successful
      and that the resulting reduction of REM-sleep had no influence on memory
      consolidation whatsoever.

PMID- 24587074
TI  - PrediQt-Cx: post treatment health related quality of life prediction model for
      cervical cancer patients.
AB  - BACKGROUND: Cervical cancer is the third largest cause of cancer mortality in
      India. The objectives of the study were to compare the pre and the post treatment
      quality of life in cervical cancer patients and to develop a prediction model to
      provide an insight into the possibilities in the treatment modules.
      METHODOLOGY/PRINCIPAL FINDINGS: A total of 198 patients were assessed with two
      structured questionnaires of Health Related Quality of Life (The European
      Organisation for Research and Treatment of Cancer, EORTC QLQ C-30 and CX-24). The
      baseline observations were recorded when the patients first reported (T1) and
      second evaluation was done at 6 months post treatment (T2). The mean age of
      detection was 50.9 years with the literacy level being non-educated or less than
      high school. Majority of them were married/cohabiting 179 (90.4%). On
      histopathological examination (HPE) squamous cell carcinoma was found to be the
      most common cell type carcinoma 147 (74.2%) followed by Adenocarcinoma 31
      (15.7%). Radical hysterectomy was the most common treatment modality 76 (38.4%),
      followed by Wertheims Hysterectomy 46 (23.2%) and Radiochemotherapy 59 (29.8%).
      The mean score of global health of cervical cancer patients post treatment was
      77.90, which was significantly higher than the pre - treatment score (54.32).
      Mean "symptoms score" post treatment was 21.69 with an aggravation of 7.32
      compared to pre treatment scores. Patients experienced substantial decrease in
      sexual activity post treatment. CONCLUSIONS/SIGNIFICANCE: The prediction
      model(PrediQt-Cx), based on Support Vector Machine(SVM) for predicting post
      treatment HRQoL in cervical cancer patients was developed and internally cross
      validated. After external validation PrediQt-Cx can be easily employed to support
      decision making by clinicians and patients from north India region, through
      openly made available for access at http://prediqt.org.

PMID- 24587075
TI  - The prevalence and molecular spectrum of alpha- and beta-globin gene mutations in
      14,332 families of Guangdong Province, China.
AB  - OBJECTIVE: To reveal the familial prevalence and molecular variation of alpha-
      and beta-globin gene mutations in Guangdong Province. METHODS: A total of 40,808
      blood samples from 14,332 families were obtained and analyzed for both
      hematological and molecular parameters. RESULTS: A high prevalence of alpha- and
      beta-globin gene mutations was found. Overall, 17.70% of pregnant women, 15.94%
      of their husbands, 16.03% of neonates, and 16.83% of couples (pregnant women and
      their husbands) were heterozygous carriers of alpha- or beta-thalassemia. The
      regions with the highest prevalence were the mountainous and western regions,
      followed by the Pearl River Delta; the region with the lowest prevalence was
      Chaoshan. The total familial carrier rate (both spouses were alpha- or beta
      thalassemia carriers) was 1.87%, and the individual carrier rates of alpha- and
      beta-thalassemia were 1.68% and 0.20%, respectively. The total rate of moderate
      to-severe fetal thalassemia was 12.78% among couples in which both parents were
      carriers. CONCLUSIONS: There was a high prevalence of alpha- and beta-thalassemia
      in Guangdong Province. This study will contribute to the development of
      thalassemia prevention and control strategies in Guangdong Province.

PMID- 24587076
TI  - Hydrogen sulfide inhibits formaldehyde-induced endoplasmic reticulum stress in
      PC12 cells by upregulation of SIRT-1.
AB  - BACKGROUND: Formaldehyde (FA), a well-known environmental pollutant, has been
      classified as a neurotoxic molecule. Our recent data demonstrate that hydrogen
      sulfide (H2S), the third gaseous transmitter, has a protective effect on the
      neurotoxicity of FA. However, the exact mechanisms underlying this protection
      remain largely unknown. Endoplasmic reticulum (ER) stress has been implicated in
      the neurotoxicity of FA. Silent mating type information regulator 2 homolog 1
      (SIRT-1), a histone deacetylases, has various biological activities, including
      the extension of lifespan, the modulation of ER stress, and the neuroprotective
      action. OBJECTIVE: We hypothesize that the protection of H2S against FA-induced
      neurotoxicity involves in inhibiting ER stress by upregulation of SIRT-1. The
      present study attempted to investigate the protective effect of H2S on FA-induced
      ER stress in PC12 cells and the contribution of SIRT-1 to the protection of H2S
      against FA-induced injuries, including ER stress, cytotoxicity and apoptosis.
      PRINCIPAL FINDINGS: We found that exogenous application of sodium hydrosulfide
      (NaHS; an H2S donor) significantly attenuated FA-induced ER stress responses,
      including the upregulated levels of glucose-regulated protein 78, C/EBP
      homologous protein, and cleaved caspase-12 expression. We showed that NaHS
      upregulates the expression of SIRT-1 in PC12 cells. Moreover, the protective
      effects of H2S on FA-elicited ER stress, cytotoxicity and apoptosis were reversed
      by Sirtinol, a specific inhibitor of SIRT-1. CONCLUSION/SIGNIFICANCE: These data
      indicate that H2S exerts its protection against the neurotoxicity of FA through
      overcoming ER stress via upregulation of SIRT-1. Our findings provide novel
      insights into the protective mechanisms of H2S against FA-induced neurotoxicity.

PMID- 24587077
TI  - Predictive factors of cytomegalovirus seropositivity among pregnant women in
      Paris, France.
AB  - BACKGROUND: Cytomegalovirus (CMV) is the most frequent cause of congenital
      infection. The objective of this study was to evaluate predictive factors for CMV
      seronegativity in a cohort of pregnant women in Paris, France. METHODS: Pregnant
      women enrolled in a prospective cohort during the 2009 A/H1N1 pandemic were
      tested for CMV IgG antibodies. Variables collected were age, geographic origin,
      lifestyle, work characteristics, socioeconomic status, gravidity, parity and
      number of children at home. A multivariate logistic regression model was used to
      identify independent predictive factors for CMV seropositivity. RESULTS: Among
      the 826 women enrolled, 389 (47.1%) were primiparous, and 552 (67.1%) had
      Metropolitan France as a geographic origin. Out of these, 355 (i.e. 57.0%, 95%
      confidence interval (CI): [53.6%-60.4%]) were CMV seropositive: 43.7% (95%
      CI:[39.5%-47.9%]) in those whose geographic origin was Metropolitan France and
      84.1% in those with other origins (95% CI:[79.2%-88.3%]). Determinants associated
      with CMV seropositivity in a multivariate logistic regression model were: (i)
      geographic origin (p<0.001(compared with Metropolitan France, geographic origins
      of Africa adjusted odds ratio (aOR) 21.2, 95% CI:[9.7-46.5], French overseas
      departments and territories and other origin, aOR 7.5, 95% CI:[3.9-14.6], and
      Europe or Asia, aOR 2.2, 95% CI: [1.3-3.7]); and (ii) gravidity (p = 0.019),
      (compared with gravidity = 1, if gravidity>=3, aOR = 1.5, 95% CI: [1.1-2.2]; if
      gravidity = 2, aOR = 1.0, 95% CI: [0.7-1.4]). Work characteristics and
      socioeconomic status were not independently associated with CMV seropositivity.
      CONCLUSIONS: In this cohort of pregnant women, a geographic origin of
      Metropolitan France and a low gravidity were predictive factors for CMV low
      seropositivity. Such women are therefore the likely target population for
      prevention of CMV infection during pregnancy in France.

PMID- 24587078
TI  - Crossmodal interactions during affective picture processing.
AB  - "Natural" crossmodal correspondences, such as the spontaneous tendency to
      associate high pitches with high spatial locations, are often hypothesized to
      occur preattentively and independently of task instructions (top-down attention).
      Here, we investigate bottom-up attentional engagement by using emotional scenes
      that are known to naturally and reflexively engage attentional resources. We
      presented emotional (pleasant and unpleasant) or neutral pictures either below or
      above a fixation cross, while participants were required to discriminate between
      a high or a low pitch tone (experiment 1). Results showed that despite a robust
      crossmodal attentional capture of task-irrelevant emotional pictures, the general
      advantage in classifying the tones for congruent over incongruent visual-auditory
      stimuli was similar for emotional and neutral pictures. On the other hand, when
      picture position was task-relevant (experiment 2), task-irrelevant tones did not
      interact with pictures with regard to their combination of pitch and visual
      vertical spatial position, but instead they were effective in minimizing the
      interference effect of emotional picture processing on the ongoing task. These
      results provide constraints on our current understanding of natural crossmodal
      correspondences. 

PMID- 24587079
TI  - Anxiety symptoms in 74+ community-dwelling elderly: associations with physical
      morbidity, depression and alcohol consumption.
AB  - OBJECTIVE: Anxiety among community-dwelling older adults has not been studied
      sufficiently. The aims of this cross-sectional population-based study were to
      estimate the point prevalence of clinically relevant anxiety symptoms and to
      describe their socio-demographic and clinical features, with particular focus on
      the association with somatic illnesses. METHODS: Three-hundred-sixty-six non
      demented older adults (mean age 83.7+/-6.2, range 74-99 years) from the Faenza
      Project (Northern Italy) were assessed using the Cambridge Mental Disorders of
      the Elderly Examination-Revised (CAMDEX-R) and the Geriatric Anxiety Inventory
      short form (GAI-sf). Multi-adjusted regression analyses were used to estimate
      Odds Ratio (OR) and 95% Confidence Intervals (95% CI). RESULTS: Clinically
      relevant anxiety symptoms occurred in one out of five participants (point
      prevalence 21.0%) and were significantly associated with depression (OR 5.6 per
      rank; 95% CI: 3.1-10.1), physical morbidity (OR 3.5 per illness; 95% CI: 1.0
      11.9) and female gender (OR 2.8; 95% CI: 1.4-5.5). Further, there were
      significant associations with a consumption of alcohol exceeding 1 alcoholic
      unit/day. CONCLUSIONS: Anxiety symptoms are very common in older subjects,
      especially when medically ill. Depression and alcohol consumption often co-occur
      with late-life anxiety symptoms, thus requiring special attention in daily
      clinical practice.

PMID- 24587080
TI  - A data-driven algorithm integrating clinical and laboratory features for the
      diagnosis and prognosis of necrotizing enterocolitis.
AB  - BACKGROUND: Necrotizing enterocolitis (NEC) is a major source of neonatal
      morbidity and mortality. Since there is no specific diagnostic test or risk of
      progression model available for NEC, the diagnosis and outcome prediction of NEC
      is made on clinical grounds. The objective in this study was to develop and
      validate new NEC scoring systems for automated staging and prognostic
      forecasting. STUDY DESIGN: A six-center consortium of university based pediatric
      teaching hospitals prospectively collected data on infants under suspicion of
      having NEC over a 7-year period. A database comprised of 520 infants was utilized
      to develop the NEC diagnostic and prognostic models by dividing the entire
      dataset into training and testing cohorts of demographically matched subjects.
      Developed on the training cohort and validated on the blind testing cohort, our
      multivariate analyses led to NEC scoring metrics integrating clinical data.
      RESULTS: Machine learning using clinical and laboratory results at the time of
      clinical presentation led to two nec models: (1) an automated diagnostic
      classification scheme; (2) a dynamic prognostic method for risk-stratifying
      patients into low, intermediate and high NEC scores to determine the risk for
      disease progression. We submit that dynamic risk stratification of infants with
      NEC will assist clinicians in determining the need for additional diagnostic
      testing and guide potential therapies in a dynamic manner. ALGORITHM
      AVAILABILITY: http://translationalmedicine.stanford.edu/cgi-bin/NEC/index.pl and
      smartphone application upon request.

PMID- 24587081
TI  - Timing of antiretroviral therapy initiation after a first AIDS-defining event:
      temporal changes in clinical attitudes in the ICONA cohort.
AB  - BACKGROUND: Time of starting antiretroviral therapy (ART) after diagnosis of
      specific AIDS-defining event (ADE) is a crucial aspect. Objectives of this study
      were to evaluate if in patients diagnosed with ADE the time to ART initiation may
      vary according to year of diagnosis and type of ADE. METHODS: All HIV+ persons
      diagnosed with an ADE over the 6 months prior to or after enrolment in the Icona
      Foundation study cohort and while ART-naive were grouped according to type of
      diagnosis: Those with ADE requiring medications interacting with ART [group A],
      those with ADE treatable only with ART [B] and other ADE [C]. Survival analysis
      by Kaplan-Meier was used to estimate the percentage of people starting ART,
      overall and after stratification for calendar period and ADE group. Multivariable
      Cox regression model was used to investigate association between calendar year of
      specific ADE and time to ART initiation. RESULTS: 720 persons with first ADE were
      observed over 1996-2013 (group A, n=171; B, n=115; C, n=434). By 30 days from
      diagnosis, 27% (95% CI: 22-32) of those diagnosed in 1996-2000 had started ART
      vs. 32% (95% CI: 24-40) in 2001-2008 and 43% (95% CI: 33-47) after 2008 (log-rank
      p=0.001). The proportion of patients starting ART by 30 days was 13% (95% CI 7
      19), 40% (95% CI: 30-50) and 38% (95% CI 33-43) in ADE groups A, B and C (log
      rank p=0.0001). After adjustment for potential confounders, people diagnosed
      after 2008 remained at increased probability of starting ART more promptly than
      those diagnosed in 1996-1999 (AHR 1.72 (95% CI 1.16-2.56). CONCLUSIONS: In our
      "real-life" setting, the time from ADE to ART initiation was significantly
      shorter in people diagnosed in more recent years, although perhaps less prompt
      than expected.

PMID- 24587082
TI  - Escherichia coli response to uranyl exposure at low pH and associated protein
      regulations.
AB  - Better understanding of uranyl toxicity in bacteria is necessary to optimize
      strains for bioremediation purposes or for using bacteria as biodetectors for
      bioavailable uranyl. In this study, after different steps of optimization,
      Escherichia coli cells were exposed to uranyl at low pH to minimize uranyl
      precipitation and to increase its bioavailability. Bacteria were adapted to mid
      acidic pH before exposure to 50 or 80 uM uranyl acetate for two hours at pH~3. To
      evaluate the impact of uranium, growth in these conditions were compared and the
      same rates of cells survival were observed in control and uranyl exposed
      cultures. Additionally, this impact was analyzed by two-dimensional differential
      gel electrophoresis proteomics to discover protein actors specifically present or
      accumulated in contact with uranium.Exposure to uranium resulted in differential
      accumulation of proteins associated with oxidative stress and in the accumulation
      of the NADH/quinone oxidoreductase WrbA. This FMN dependent protein performs
      obligate two-electron reduction of quinones, and may be involved in cells
      response to oxidative stress. Interestingly, this WrbA protein presents
      similarities with the chromate reductase from E. coli, which was shown to reduce
      uranyl in vitro.

PMID- 24587083
TI  - Logopenic and nonfluent variants of primary progressive aphasia are
      differentiated by acoustic measures of speech production.
AB  - Differentiation of logopenic (lvPPA) and nonfluent/agrammatic (nfvPPA) variants
      of Primary Progressive Aphasia is important yet remains challenging since it
      hinges on expert based evaluation of speech and language production. In this
      study acoustic measures of speech in conjunction with voxel-based morphometry
      were used to determine the success of the measures as an adjunct to diagnosis and
      to explore the neural basis of apraxia of speech in nfvPPA. Forty-one patients
      (21 lvPPA, 20 nfvPPA) were recruited from a consecutive sample with suspected
      frontotemporal dementia. Patients were diagnosed using the current gold-standard
      of expert perceptual judgment, based on presence/absence of particular speech
      features during speaking tasks. Seventeen healthy age-matched adults served as
      controls. MRI scans were available for 11 control and 37 PPA cases; 23 of the PPA
      cases underwent amyloid ligand PET imaging. Measures, corresponding to perceptual
      features of apraxia of speech, were periods of silence during reading and
      relative vowel duration and intensity in polysyllable word repetition.
      Discriminant function analyses revealed that a measure of relative vowel duration
      differentiated nfvPPA cases from both control and lvPPA cases (r(2) = 0.47) with
      88% agreement with expert judgment of presence of apraxia of speech in nfvPPA
      cases. VBM analysis showed that relative vowel duration covaried with grey matter
      intensity in areas critical for speech motor planning and programming: precentral
      gyrus, supplementary motor area and inferior frontal gyrus bilaterally, only
      affected in the nfvPPA group. This bilateral involvement of frontal speech
      networks in nfvPPA potentially affects access to compensatory mechanisms
      involving right hemisphere homologues. Measures of silences during reading also
      discriminated the PPA and control groups, but did not increase predictive
      accuracy. Findings suggest that a measure of relative vowel duration from of a
      polysyllable word repetition task may be sufficient for detecting most cases of
      apraxia of speech and distinguishing between nfvPPA and lvPPA.

PMID- 24587084
TI  - Neurobiological degeneracy and affordance perception support functional intra
      individual variability of inter-limb coordination during ice climbing.
AB  - This study investigated the functional intra-individual movement variability of
      ice climbers differing in skill level to understand how icefall properties were
      used by participants as affordances to adapt inter-limb coordination patterns
      during performance. Seven expert climbers and seven beginners were observed as
      they climbed a 30 m icefall. Movement and positioning of the left and right hand
      ice tools, crampons and the climber's pelvis over the first 20 m of the climb
      were recorded and digitized using video footage from a camera (25 Hz) located
      perpendicular to the plane of the icefall. Inter-limb coordination, frequency and
      types of action and vertical axis pelvis displacement exhibited by each climber
      were analysed for the first five minutes of ascent. Participant perception of
      climbing affordances was assessed through: (i) calculating the ratio between
      exploratory movements and performed actions, and (ii), identifying, by self
      confrontation interviews, the perceptual variables of environmental properties,
      which were significant to climbers for their actions. Data revealed that experts
      used a wider range of upper and lower limb coordination patterns, resulting in
      the emergence of different types of action and fewer exploratory movements,
      suggesting that effective holes in the icefall provided affordances to regulate
      performance. In contrast, beginners displayed lower levels of functional intra
      individual variability of motor organization, due to repetitive swinging of ice
      tools and kicking of crampons to achieve and maintain a deep anchorage,
      suggesting lack of perceptual attunement and calibration to environmental
      properties to support climbing performance. 

PMID- 24587085
TI  - Finding the best thresholds of FEV1 and dyspnea to predict 5-year survival in
      COPD patients: the COCOMICS study.
AB  - BACKGROUND: FEV1 is universally used as a measure of severity in COPD. Current
      thresholds are based on expert opinion and not on evidence. OBJECTIVES: We aimed
      to identify the best FEV1 (% predicted) and dyspnea (mMRC) thresholds to predict
      5-yr survival in COPD patients. DESIGN AND METHODS: We conducted a patient-based
      pooled analysis of eleven COPD Spanish cohorts (COCOMICS). Survival analysis, ROC
      curves, and C-statistics were used to identify and compare the best FEV1 (%) and
      mMRC scale thresholds that predict 5-yr survival. RESULTS: A total of 3,633
      patients (93% men), totaling 15,878 person-yrs. were included, with a mean age
      66.4 +/- 9.7, and predicted FEV1 of 53.8% (+/- 19.4%). Overall 975 (28.1%)
      patients died at 5 years. The best thresholds that spirometrically split the COPD
      population were: mild >= 70%, moderate 56-69%, severe 36-55%, and very severe <=
      35%. Survival at 5 years was 0.89 for patients with FEV1 >= 70 vs. 0.46 in
      patients with FEV1 <= 35% (H.R: 6; 95% C.I.: 4.69-7.74). The new classification
      predicts mortality significantly better than dyspnea (mMRC) or FEV1 GOLD and BODE
      cutoffs (all p<0.001). Prognostic reliability is maintained at 1, 3, 5, and 10
      years. In younger patients, survival was similar for FEV1 (%) values between 70%
      and 100%, whereas in the elderly the relationship between FEV1 (%) and mortality
      was inversely linear. CONCLUSIONS: The best thresholds for 5-yr survival were
      obtained stratifying FEV1 (%) by >= 70%, 56-69%, 36-55%, and <= 35%. These
      cutoffs significantly better predict mortality than mMRC or FEV1 (%) GOLD and
      BODE cutoffs.

PMID- 24587086
TI  - Critical role of interferon-alpha constitutively produced in human hepatocytes in
      response to RNA virus infection.
AB  - Several viruses are known to infect human liver and cause the hepatitis, but the
      interferon (IFN) response, a first-line defense against viral infection, of virus
      infected hepatocytes is not clearly defined yet. We investigated innate immune
      system against RNA viral infection in immortalized human hepatocytes (HuS-E/2
      cells), as the cells showed similar early innate immune responses to primary
      human hepatocytes (PHH). The low-level constitutive expression of IFN-alpha1
      gene, but not IFN-beta and IFN-lambda, was observed in both PHH and HuS-E/2 cells
      in the absence of viral infection, suggesting a particular subtype(s) of IFN
      alpha is constitutively produced in human hepatocytes. To examine the functional
      role of such IFN-alpha in the antiviral response, the expression profiles of
      innate immune-related genes were studied in the cells with the treatment of
      neutralization against type I IFN receptor 2 (IFNAR2) or IFN-alpha itself to
      inhibit the constitutive IFN-alpha signaling before and after virus infection. As
      the results, a clear reduction of basal level expression of IFN-inducible genes
      was observed in uninfected cells. When the effect of the inhibition on the cells
      infected with hepatitis C virus (HCV) was examined, the significant decrease of
      IFN stimulated gene expression and the enhancement of initial HCV replication
      were observed, suggesting that the steady-state production of IFN-alpha plays a
      role in amplification of antiviral responses to control the spread of RNA viral
      infection in human hepatocytes. 

PMID- 24587087
TI  - Investigating the role of state permitting and agriculture agencies in addressing
      public health concerns related to industrial food animal production.
AB  - OBJECTIVES: Industrial food animal production (IFAP) operations adversely impact
      environmental public health through air, water, and soil contamination. We sought
      to determine how state permitting and agriculture agencies respond to these
      public health concerns. METHODS: We conducted semi-structured qualitative
      interviews with staff at 12 state agencies in seven states, which were chosen
      based on high numbers or rapid increase of IFAP operations. The interviews served
      to gather information regarding agency involvement in regulating IFAP operations,
      the frequency and type of contacts received about public health concerns, how the
      agency responds to such contacts, and barriers to additional involvement.
      RESULTS: Permitting and agriculture agencies' responses to health-based IFAP
      concerns are constrained by significant barriers including narrow regulations, a
      lack of public health expertise within the agencies, and limited resources.
      CONCLUSIONS: State agencies with jurisdiction over IFAP operations are unable to
      adequately address relevant public health concerns due to multiple factors.
      Combining these results with previously published findings on barriers facing
      local and state health departments in the same states reveals significant gaps
      between these agencies regarding public health and IFAP. There is a clear need
      for regulations to protect public health and for public health professionals to
      provide complementary expertise to agencies responsible for regulating IFAP
      operations.

PMID- 24587088
TI  - Regulatory specialization of xyloglucan (XG) and glucuronoarabinoxylan (GAX) in
      pericarp cell walls during fruit ripening in tomato (Solanum lycopersicum).
AB  - Disassembly of cell wall polysaccharides by various cell wall hydrolases during
      fruit softening causes structural changes in hemicellulose and pectin that affect
      the physical properties and softening of tomato fruit. In a previous study, we
      showed that the changes in pectin during tomato fruit ripening were unique in
      each fruit tissue. In this study, to clarify the changes in hemicellulose in
      tissues during tomato fruit ripening, we focused on glucuronoarabinoxylan (GAX)
      and xyloglucan (XG). GAX was detected only in the skin and inner epidermis of the
      pericarp using LM11 antibodies, whereas a large increase in XG was detected in
      all fruit tissues using LM15 antibodies. The activity of hemicellulose
      degradation enzymes, such as beta-xylosidase and alpha-arabinofuranosidase,
      decreased gradually during fruit ripening, although the tomato fruits continued
      to soften. In contrast, GAX and XG biosynthesis-related genes were expressed in
      all tomato fruit tissues even during ripening, indicating that XG was synthesized
      throughout the fruit and that GAX may be synthesized only in the vascular bundles
      and the inner epidermis. Our results suggest that changes in the cell wall
      architecture and tissue-specific distribution of XG and GAX might be required for
      the regulation of fruit softening and the maintenance of fruit shape. 

PMID- 24587089
TI  - Estimating oxygen needs for childhood pneumonia in developing country health
      systems: a new model for expecting the unexpected.
AB  - BACKGROUND: Planning for the reliable and cost-effective supply of a health
      service commodity such as medical oxygen requires an understanding of the dynamic
      need or 'demand' for the commodity over time. In developing country health
      systems, however, collecting longitudinal clinical data for forecasting purposes
      is very difficult. Furthermore, approaches to estimating demand for supplies
      based on annual averages can underestimate demand some of the time by missing
      temporal variability. METHODS: A discrete event simulation model was developed to
      estimate variable demand for a health service commodity using the important
      example of medical oxygen for childhood pneumonia. The model is based on five key
      factors affecting oxygen demand: annual pneumonia admission rate, hypoxaemia
      prevalence, degree of seasonality, treatment duration, and oxygen flow rate.
      These parameters were varied over a wide range of values to generate simulation
      results for different settings. Total oxygen volume, peak patient load, and hours
      spent above average-based demand estimates were computed for both low and high
      seasons. FINDINGS: Oxygen demand estimates based on annual average values of
      demand factors can often severely underestimate actual demand. For scenarios with
      high hypoxaemia prevalence and degree of seasonality, demand can exceed average
      levels up to 68% of the time. Even for typical scenarios, demand may exceed three
      times the average level for several hours per day. Peak patient load is sensitive
      to hypoxaemia prevalence, whereas time spent at such peak loads is strongly
      influenced by degree of seasonality. CONCLUSION: A theoretical study is presented
      whereby a simulation approach to estimating oxygen demand is used to better
      capture temporal variability compared to standard average-based approaches. This
      approach provides better grounds for health service planning, including decision
      making around technologies for oxygen delivery. Beyond oxygen, this approach is
      widely applicable to other areas of resource and technology planning in
      developing country health systems.

PMID- 24587090
TI  - Hypoxia exerts dualistic effects on inflammatory and proliferative responses of
      healthy and asthmatic primary human bronchial smooth muscle cells.
AB  - BACKGROUND: For oxygen supply, airway wall cells depend on diffusion though the
      basement membrane, as well as on delivery by micro-vessels. In the asthmatic
      lung, local hypoxic conditions may occur due to increased thickness and altered
      composition of the basement membrane, as well as due to edema of the inflamed
      airway wall. OBJECTIVE: In our study we investigated the effect of hypoxia on
      proliferation and pro-inflammatory and pro-angiogenic parameter production by
      human bronchial smooth muscle cells (BSMC). Furthermore, conditioned media of
      hypoxia-exposed BSMC was tested for its ability to induce sprout outgrowth from
      endothelial cells spheroids. METHODS: BSMC were cultured in RPMI1640 (5% FCS)
      under normoxic (21% O2) and hypoxic (1% and 5% O2) conditions. Proliferation was
      determined by cell count and Western blot analysis for cyclin E and Proliferating
      Cell Nuclear Antigen (PCNA). Secretion of IL-6, IL-8, ENA-78 and VEGF-A was
      analyzed by ELISA. BSMC conditioned medium was tested for its angiogenic capacity
      by endothelial cell (EC)-spheroid in vitro angiogenesis assay. RESULTS:
      Proliferation of BSMC obtained from asthmatic and non-asthmatic patients was
      significantly reduced in the presence of 1% O2, whereas 5% O2 reduced
      proliferation of asthmatic BSMC only. Hypoxia induced HIF-1alpha expression in
      asthmatic and non-asthmatic BSMC, which coincided with significantly increased
      release of IL-6, IL-8 and VEGF-A, but not ENA-78. Finally, endothelial sprout
      outgrowth from EC spheroids was increased when exposed to hypoxia conditioned
      BSMC medium. CONCLUSION: Hypoxia had dualistic effects on proliferative and
      inflammatory responses of asthmatic and non-asthmatic BSMC. First, hypoxia
      reduced BSMC proliferation. Second, hypoxia induced a pro-inflammatory, pro
      angiogenic response. BSMC and EC may thus be promising new targets to counteract
      and/or alleviate airway wall remodeling.

PMID- 24587091
TI  - Do photobiont switch and cephalodia emancipation act as evolutionary drivers in
      the lichen symbiosis? A case study in the Pannariaceae (Peltigerales).
AB  - Lichen symbioses in the Pannariaceae associate an ascomycete and either
      cyanobacteria alone (usually Nostoc; bipartite thalli) or green algae and
      cyanobacteria (cyanobacteria being located in dedicated structures called
      cephalodia; tripartite thalli) as photosynthetic partners (photobionts). In
      bipartite thalli, cyanobacteria can either be restricted to a well-delimited
      layer within the thallus ('pannarioid' thalli) or spread over the thallus that
      becomes gelatinous when wet ('collematoid' thalli). We studied the collematoid
      genera Kroswia and Physma and an undescribed tripartite species along with
      representatives of the pannarioid genera Fuscopannaria, Pannaria and Parmeliella.
      Molecular inferences from 4 loci for the fungus and 1 locus for the photobiont
      and statistical analyses within a phylogenetic framework support the following:
      (a) several switches from pannarioid to collematoid thalli occured and are
      correlated with photobiont switches; the collematoid genus Kroswia is nested
      within the pannarioid genus Fuscopannaria and the collematoid genus Physma is
      sister to the pannarioid Parmeliella mariana group; (b) Nostoc associated with
      collematoid thalli in the Pannariaceae are related to that of the Collemataceae
      (which contains only collematoid thalli), and never associated with pannarioid
      thalli; Nostoc associated with pannarioid thalli also associate in other families
      with similar morphology; (c) ancestors of several lineages in the Pannariaceae
      developed tripartite thalli, bipartite thalli probably resulting from cephalodia
      emancipation from tripartite thalli which eventually evolved and diverged, as
      suggested by the same Nostoc present in the collematoid genus Physma and in the
      cephalodia of a closely related tripartite species; Photobiont switches and
      cephalodia emancipation followed by divergence are thus suspected to act as
      evolutionary drivers in the family Pannariaceae. 

PMID- 24587092
TI  - Tuberculosis epidemiology and selection in an autochthonous Siberian population
      from the 16th-19th century.
AB  - Tuberculosis is one of most ancient diseases affecting human populations.
      Although numerous studies have tried to detect pathogenic DNA in ancient
      skeletons, the successful identification of ancient tuberculosis strains remains
      rare. Here, we describe a study of 140 ancient subjects inhumed in Yakutia
      (Eastern Siberia) during a tuberculosis outbreak, dating from the 16(th)-19(th)
      century. For a long time, Yakut populations had remained isolated from European
      populations, and it was not until the beginning of the 17(th) century that first
      contacts were made with European settlers. Subsequently, tuberculosis spread
      throughout Yakutia, and the evolution of tuberculosis frequencies can be tracked
      until the 19(th) century. This study took a multidisciplinary approach, examining
      historical and paleo-epidemiological data to understand the impact of
      tuberculosis on ancient Yakut population. In addition, molecular identification
      of the ancient tuberculosis strain was realized to elucidate the natural history
      and host-pathogen co-evolution of human tuberculosis that was present in this
      population. This was achieved by the molecular detection of the IS6110 sequence
      and SNP genotyping by the SNaPshot technique. Results demonstrated that the
      strain belongs to cluster PGG2-SCG-5, evocating a European origin. Our study
      suggests that the Yakut population may have been shaped by selection pressures,
      exerted by several illnesses, including tuberculosis, over several centuries.
      This confirms the validity and necessity of using a multidisciplinary approach to
      understand the natural history of Mycobacterium tuberculosis infection and
      disease. 

PMID- 24587093
TI  - Targeted recombinant fusion proteins of IFNgamma and mimetic IFNgamma with
      PDGFbetaR bicyclic peptide inhibits liver fibrogenesis in vivo.
AB  - Hepatic stellate cells (HSCs), following transdifferentiation to myofibroblasts
      plays a key role in liver fibrosis. Therefore, attempts to attenuate this
      myofibroblastic phenotype would be a promising therapeutic approach. Interferon
      gamma (IFNgamma) is a potent anti-fibrotic cytokine, but its pleiotropic receptor
      expression leading to severe adverse effects has limited its clinical
      application. Since, activated HSC express high-level of platelet derived growth
      factor beta receptor (PDGFbetaR), we investigated the potential of PDGFbetaR
      specific targeting of IFNgamma and its signaling peptide that lacks IFNgammaR
      binding site (mimetic IFNgamma or mimIFNgamma) in liver fibrosis. We prepared DNA
      constructs expressing IFNgamma, mimIFNgamma or BiPPB (PDGFbetaR-specific bicyclic
      peptide)-IFNgamma, BiPPB-mimIFNgamma fusion proteins. Both chimeric proteins
      alongwith IFNgamma and mimIFNgamma were produced in E.coli. The expressed
      proteins were purified and analyzed for PDGFbetaR-specific binding and in vitro
      effects. Subsequently, these recombinant proteins were investigated for the liver
      uptake (pSTAT1alpha signaling pathway), for anti-fibrotic effects and adverse
      effects (platelet counts) in CCl4-induced liver fibrogenesis in mice. The
      purified HSC-targeted IFNgamma and mimIFNgamma fusion proteins showed PDGFbetaR
      specific binding and significantly reduced TGFbeta-induced collagen-I expression
      in human HSC (LX2 cells), while mouse IFNgamma and mimIFNgamma did not show any
      effect. Conversely, mouse IFNgamma and BiPPB-IFNgamma induced activation and dose
      dependent nitric oxide release in mouse macrophages (express IFNgammaR while lack
      PDGFbetaR), which was not observed with mimIFNgamma and BiPPB-mimIFNgamma, due to
      the lack of IFNgammaR binding sites. In vivo, targeted BiPPB-IFNgamma and BiPPB
      mimIFNgamma significantly activated intrahepatic IFNgamma-signaling pathway
      compared to IFNgamma and mimIFNgamma suggesting increased liver accumulation.
      Furthermore, the targeted fusion proteins ameliorated liver fibrogenesis in mice
      by significantly reducing collagen and alpha-SMA expression and potentiating
      collagen degradation. IFNgamma also induced reduction in fibrogenesis but showed
      significant decrease in platelet counts, which was restored with targeted
      proteins. These results suggest that these rationally designed proteins can be
      further developed as novel anti-fibrotic therapeutics. 

PMID- 24587094
TI  - Frequency of vital signs monitoring and its association with mortality among
      adults with severe sepsis admitted to a general medical ward in Uganda.
AB  - INTRODUCTION: Optimal vital signs monitoring of patients with severe sepsis in
      resource-limited settings may improve outcomes. The objective of this study was
      to determine the frequency of vital signs monitoring of patients with severe
      sepsis and its association with mortality in a regional referral hospital in
      Uganda. METHODS: We reviewed medical records of patients admitted to Mbarara
      Regional Referral Hospital in Southwestern Uganda with severe sepsis defined by
      the presence of infection plus >= 2 of the systemic inflammatory response
      syndrome criteria, and >= 1 organ dysfunction (altered mental state, hypotension,
      jaundice, or thrombocytopenia). We recorded frequency of vital signs monitoring
      in addition to socio-demographic, clinical, and outcome data. We analyzed the
      data using logistic regression. RESULTS: We identified 202 patients with severe
      sepsis. The median age was 35 years (IQR, 25-47) and 98 (48%) were female. HIV
      infection and anemia was present in 115 (57%) and 83 (41%) patients respectively.
      There were 67 (33%) in-hospital deaths. The median monitoring frequency per day
      was 1.1 (IQR 0.9-1.5) for blood pressure, 1.0 (IQR, 0.8-1.3) for temperature and
      pulse, and 0.5 (IQR, 0.3-1.0) for respiratory rate. The frequency of vital signs
      monitoring decreased during the course of hospitalization. Patients who died had
      a higher frequency of vital signs monitoring (p<0.05). The admission respiratory
      rate was associated with both frequency of monitoring (coefficient of linear
      regression 0.6, 95% CI 0.5-0.8, p<0.001) and mortality (AOR 2.5, 95% CI 1.3-5.3,
      p = 0.01). Other predictors of mortality included severity of illness, HIV
      infection, and anemia (p<0.05). CONCLUSIONS: More research is needed to determine
      the optimal frequency of vital signs monitoring for severely septic patients in
      resource-limited settings such as Uganda.

PMID- 24587095
TI  - Cadherin-11 in renal cell carcinoma bone metastasis.
AB  - Bone is one of the common sites of metastases from renal cell carcinoma (RCC),
      however the mechanism by which RCC preferentially metastasize to bone is poorly
      understood. Homing/retention of RCC cells to bone and subsequent proliferation
      are necessary steps for RCC cells to colonize bone. To explore possible
      mechanisms by which these processes occur, we used an in vivo metastasis model in
      which 786-O RCC cells were injected into SCID mice intracardially, and
      organotropic cell lines from bone, liver, and lymph node were selected. The
      expression of molecules affecting cell adhesion, angiogenesis, and osteolysis
      were then examined in these selected cells. Cadherin-11, a mesenchymal cadherin
      mainly expressed in osteoblasts, was significantly increased on the cell surface
      in bone metastasis-derived 786-O cells (Bo-786-O) compared to parental, liver, or
      lymph node-derived cells. In contrast, the homing receptor CXCR4 was equivalently
      expressed in cells derived from all organs. No significant difference was
      observed in the expression of angiogenic factors, including HIF-1alpha, VEGF,
      angiopoeitin-1, Tie2, c-MET, and osteolytic factors, including PTHrP, IL-6 and
      RANKL. While the parental and Bo-786-O cells have similar proliferation rates, Bo
      786-O cells showed an increase in migration compared to the parental 786-O cells.
      Knockdown of Cadherin-11 using shRNA reduced the rate of migration in Bo-786-O
      cells, suggesting that Cadherin-11 contributes to the increased migration
      observed in bone-derived cells. Immunohistochemical analysis of cadherin-11
      expression in a human renal carcinoma tissue array showed that the number of
      human specimens with positive cadherin-11 activity was significantly higher in
      tumors that metastasized to bone than that in primary tumors. Together, these
      results suggest that Cadherin-11 may play a role in RCC bone metastasis. 

PMID- 24587096
TI  - An enteroendocrine cell-enteric glia connection revealed by 3D electron
      microscopy.
AB  - The enteroendocrine cell is the cornerstone of gastrointestinal chemosensation.
      In the intestine and colon, this cell is stimulated by nutrients, tastants that
      elicit the perception of flavor, and bacterial by-products; and in response, the
      cell secretes hormones like cholecystokinin and peptide YY--both potent
      regulators of appetite. The development of transgenic mice with enteroendocrine
      cells expressing green fluorescent protein has allowed for the elucidation of the
      apical nutrient sensing mechanisms of the cell. However, the basal secretory
      aspects of the enteroendocrine cell remain largely unexplored, particularly
      because a complete account of the enteroendocrine cell ultrastructure does not
      exist. Today, the fine ultrastructure of a specific cell can be revealed in the
      third dimension thanks to the invention of serial block face scanning electron
      microscopy (SBEM). Here, we bridged confocal microscopy with SBEM to identify the
      enteroendocrine cell of the mouse and study its ultrastructure in the third
      dimension. The results demonstrated that 73.5% of the peptide-secreting vesicles
      in the enteroendocrine cell are contained within an axon-like basal process. We
      called this process a neuropod. This neuropod contains neurofilaments, which are
      typical structural proteins of axons. Surprisingly, the SBEM data also
      demonstrated that the enteroendocrine cell neuropod is escorted by enteric glia-
      the cells that nurture enteric neurons. We extended these structural findings
      into an in vitro intestinal organoid system, in which the addition of glial
      derived neurotrophic factors enhanced the development of neuropods in
      enteroendocrine cells. These findings open a new avenue of exploration in
      gastrointestinal chemosensation by unveiling an unforeseen physical relationship
      between enteric glia and enteroendocrine cells.

PMID- 24587097
TI  - Pharmacokinetics of natural and engineered secreted factors delivered by
      mesenchymal stromal cells.
AB  - Transient cell therapy is an emerging drug class that requires new approaches for
      pharmacological monitoring during use. Human mesenchymal stem cells (MSCs) are a
      clinically-tested transient cell therapeutic that naturally secrete anti
      inflammatory factors to attenuate immune-mediated diseases. MSCs were used as a
      proof-of-concept with the hypothesis that measuring the release of secreted
      factors after cell transplantation, rather than the biodistribution of the cells
      alone, would be an alternative monitoring tool to understand the exposure of a
      subject to MSCs. By comparing cellular engraftment and the associated serum
      concentration of secreted factors released from the graft, we observed clear
      differences between the pharmacokinetics of MSCs and their secreted factors.
      Exploration of the effects of natural or engineered secreted proteins, active
      cellular secretion pathways, and clearance mechanisms revealed novel aspects that
      affect the systemic exposure of the host to secreted factors from a cellular
      therapeutic. We assert that a combined consideration of cell delivery strategies
      and molecular pharmacokinetics can provide a more predictive model for outcomes
      of MSC transplantation and potentially other transient cell therapeutics. 

PMID- 24587098
TI  - VelC positively controls sexual development in Aspergillus nidulans.
AB  - Fungal development and secondary metabolism is intimately associated via
      activities of the fungi-specific velvet family proteins including VeA, VosA, VelB
      and VelC. Among these, VelC has not been characterized in Aspergillus nidulans.
      In this study, we characterize the role of VelC in asexual and sexual development
      in A. nidulans. The velC mRNA specifically accumulates during the early phase of
      sexual development. The deletion of velC leads to increased number of conidia and
      reduced production of sexual fruiting bodies (cleistothecia). In the velC
      deletion mutant, mRNA levels of the brlA, abaA, wetA and vosA genes that control
      sequential activation of asexual sporulation increase. Overexpression of velC
      causes increased formation of cleistothecia. These results suggest that VelC
      functions as a positive regulator of sexual development. VelC is one of the five
      proteins that physically interact with VosA in yeast two-hybrid and GST pull down
      analyses. The DeltavelC DeltavosA double mutant produced fewer cleistothecia and
      behaved similar to the DeltavosA mutant, suggesting that VosA is epistatic to
      VelC in sexual development, and that VelC might mediate control of sex through
      interacting with VosA at specific life stages for sexual fruiting. 

PMID- 24587099
TI  - Does animal-mediated seed dispersal facilitate the formation of Pinus armandii
      Quercus aliena var. acuteserrata forests?
AB  - The Pinus armandii and Quercus aliena var. acuteserrata mixed forest is one of
      the major forest types in the Qinling Mountains, China. P. armandii is considered
      to be a pioneer species during succession and it is usually invaded by late
      successional Q. aliena var. acuteserrata. However, the mechanism that underlies
      its invasion remains unclear. In the present study, we tracked seed dispersal of
      P. armandii and Q. aliena var. acuteserrata using coded plastic tags in the
      western, middle and eastern Qinling Mountains to elucidate the invasion process
      in the mixed forests. Our results indicated that the seeds of both P. armandii
      and Q. aliena var. acuteserrata were removed rapidly in the Qinling Mountains,
      and there were no differences in the seed removal rates between the two species.
      There were significant differences in rodent seed-eating and caching strategies
      between the two tree species. For P. armandii, seeds were more likely to be eaten
      in situ than those of Q. aliena var. acuteserrata in all plots. By contrast, the
      acorns of Q. aliena var. acuteserrata were less frequently eaten in situ, but
      more likely to be removed and cached. Q. aliena var. acuteserrata acorns had
      significantly longer dispersal distances than P. armandii seeds in all plots.
      Although P. armandii seeds were less likely to be dispersed into the Q. aliena
      var. acuteserrata stands, over 30% of the released acorns were transported into
      the P. armandii stands where they established five seedlings. Based on the
      coupled recruitment patterns of P. armandii and Q. aliena var. acuteserrata, we
      suggest that the animal-mediated seed dispersal contributes to the formation of
      Pinus armandii-Quercus aliena var. acuteserrata forests. 

PMID- 24587100
TI  - Quantitative field testing Heterodera glycines from metagenomic DNA samples
      isolated directly from soil under agronomic production.
AB  - A quantitative PCR procedure targeting the Heterodera glycines ortholog of the
      Caenorhabditis elegans uncoordinated-78 gene was developed. The procedure
      estimated the quantity of H. glycines from metagenomic DNA samples isolated
      directly from field soil under agronomic production. The estimation of H.
      glycines quantity was determined in soil samples having other soil dwelling plant
      parasitic nematodes including Hoplolaimus, predatory nematodes including
      Mononchus, free-living nematodes and biomass. The methodology provides a
      framework for molecular diagnostics of nematodes from metagenomic DNA isolated
      directly from field soil. 

PMID- 24587101
TI  - Assessment of iron deposition and white matter maturation in infant brains by
      using enhanced T2 star weighted angiography (ESWAN): R2* versus phase values.
AB  - BACKGROUND AND PURPOSE: Iron deposition and white matter (WM) maturation are very
      important for brain development in infants. It has been reported that the R2* and
      phase values originating from the gradient-echo sequence could both reflect the
      iron and myelination. The aim of this study was to investigate age-related
      changes of R2* and phase value, and compare their performances for monitoring
      iron deposition and WM maturation in infant brains. METHODS: 56 infants were
      examined by enhanced T2 star weighted angiography (ESWAN) and diffusion tensor
      imaging in the 1.5T MRI system. The R2* and phase values were measured from the
      deep gray nuclei and WM. Fractional anisotropy (FA) values were measured only in
      the WM regions. Correlation analyses were performed to explore the relation among
      the two parameters (R2* and phase values) and postmenstrual age (PMA), previously
      published iron concentrations as well as FA values. RESULTS: We found
      significantly positive correlations between the R2* values and PMA in both of the
      gray nuclei and WM. Moreover, R2* values had a positive correlation with the iron
      reference concentrations in the deep gray nuclei and the FA in the WM. However,
      phase values only had the positive correlation with PMA and FA in the internal
      capsule, and no significant correlation with PMA and iron content in the deep
      gray nuclei. CONCLUSIONS: Compared with the phase values, R2* may be a preferable
      method to estimate the iron deposition and WM maturation in infant brains.

PMID- 24587102
TI  - A porphodimethene chemical inhibitor of uroporphyrinogen decarboxylase.
AB  - Uroporphyrinogen decarboxylase (UROD) catalyzes the conversion of
      uroporphyrinogen to coproporphyrinogen during heme biosynthesis. This enzyme was
      recently identified as a potential anticancer target; its inhibition leads to an
      increase in reactive oxygen species, likely mediated by the Fenton reaction,
      thereby decreasing cancer cell viability and working in cooperation with
      radiation and/or cisplatin. Because there is no known chemical UROD inhibitor
      suitable for use in translational studies, we aimed to design, synthesize, and
      characterize such a compound. Initial in silico-based design and docking analyses
      identified a potential porphyrin analogue that was subsequently synthesized. This
      species, a porphodimethene (named PI-16), was found to inhibit UROD in an
      enzymatic assay (IC50 = 9.9 uM), but did not affect porphobilinogen deaminase (at
      62.5 uM), thereby exhibiting specificity. In cellular assays, PI-16 reduced the
      viability of FaDu and ME-180 cancer cells with half maximal effective
      concentrations of 22.7 uM and 26.9 uM, respectively, and only minimally affected
      normal oral epithelial (NOE) cells. PI-16 also combined effectively with
      radiation and cisplatin, with potent synergy being observed in the case of
      cisplatin in FaDu cells (Chou-Talalay combination index <1). This work presents
      the first known synthetic UROD inhibitor, and sets the foundation for the design,
      synthesis, and characterization of higher affinity and more effective UROD
      inhibitors.

PMID- 24587103
TI  - Evaluation of sequence features from intrinsically disordered regions for the
      estimation of protein function.
AB  - With the exponential increase in the number of sequenced organisms, automated
      annotation of proteins is becoming increasingly important. Intrinsically
      disordered regions are known to play a significant role in protein function.
      Despite their abundance, especially in eukaryotes, they are rarely used to inform
      function prediction systems. In this study, we extracted seven sequence features
      in intrinsically disordered regions and developed a scheme to use them to predict
      Gene Ontology Slim terms associated with proteins. We evaluated the function
      prediction performance of each feature. Our results indicate that the residue
      composition based features have the highest precision while bigram probabilities,
      based on sequence profiles of intrinsically disordered regions obtained from
      PSIBlast, have the highest recall. Amino acid bigrams and features based on
      secondary structure show an intermediate level of precision and recall. Almost
      all features showed a high prediction performance for GO Slim terms related to
      extracellular matrix, nucleus, RNA and DNA binding. However, feature performance
      varied significantly for different GO Slim terms emphasizing the need for a
      unique classifier optimized for the prediction of each functional term. These
      findings provide a first comprehensive and quantitative evaluation of sequence
      features in intrinsically disordered regions and will help in the development of
      a more informative protein function predictor. 

PMID- 24587104
TI  - A functional imaging study of self-regulatory capacities in persons who stutter.
AB  - Developmental stuttering is a disorder of speech fluency with an unknown
      pathogenesis. The similarity of its phenotype and natural history with other
      childhood neuropsychiatric disorders of frontostriatal pathology suggests that
      stuttering may have a closely related pathogenesis. We investigated in this study
      the potential involvement of frontostriatal circuits in developmental stuttering.
      We collected functional magnetic resonance imaging data from 46 persons with
      stuttering and 52 fluent controls during performance of the Simon Spatial
      Incompatibility Task. We examined differences between the two groups of blood
      oxygen-level-dependent activation associated with two neural processes, the
      resolution of cognitive conflict and the context-dependent adaptation to changes
      in conflict. Stuttering speakers and controls did not differ on behavioral
      performance on the task. In the presence of conflict-laden stimuli, however,
      stuttering speakers activated more strongly the cingulate cortex, left anterior
      prefrontal cortex, right medial frontal cortex, left supplementary motor area,
      right caudate nucleus, and left parietal cortex. The magnitude of activation in
      the anterior cingulate cortex correlated inversely in stuttering speakers with
      symptom severity. Stuttering speakers also showed blunted activation during
      context-dependent adaptation in the left dorsolateral prefrontal cortex, a brain
      region that mediates cross-temporal contingencies. Frontostriatal hyper
      responsivity to conflict resembles prior findings in other disorders of
      frontostriatal pathology, and therefore likely represents a general mechanism
      supporting functional compensation for an underlying inefficiency of neural
      processing in these circuits. The reduced activation of dorsolateral prefrontal
      cortex likely represents the inadequate readiness of stuttering speakers to
      execute a sequence of motor responses. 

PMID- 24587105
TI  - Use of synthetic isoprenoids to target protein prenylation and Rho GTPases in
      breast cancer invasion.
AB  - Dysregulation of Ras and Rho family small GTPases drives the invasion and
      metastasis of multiple cancers. For their biological functions, these GTPases
      require proper subcellular localization to cellular membranes, which is regulated
      by a series of post-translational modifications that result in either
      farnesylation or geranylgeranylation of the C-terminal CAAX motif. This concept
      provided the rationale for targeting farnesyltransferase (FTase) and
      geranylgeranyltransferases (GGTase) for cancer treatment. However, the resulting
      prenyl transferase inhibitors have not performed well in the clinic due to issues
      with alternative prenylation and toxicity. As an alternative, we have developed a
      unique class of potential anti-cancer therapeutics called Prenyl Function
      Inhibitors (PFIs), which are farnesol or geranyl-geraniol analogs that act as
      alternate substrates for FTase or GGTase. Here, we test the ability of our lead
      PFIs, anilinogeraniol (AGOH) and anilinofarnesol (AFOH), to block the invasion of
      breast cancer cells. We found that AGOH treatment effectively decreased invasion
      of MDA-MB-231 cells in a two-dimensional (2D) invasion assay at 100 uM while it
      blocked invasive growth in three-dimensional (3D) culture model at as little as
      20 uM. Notably, the effect of AGOH on 3D invasive growth was phenocopied by
      electroporation of cells with C3 exotransferase. To determine if RhoA and RhoC
      were direct targets of AGOH, we performed Rho activity assays in MDA-MB-231 and
      MDA-MB-468 cells and found that AGOH blocked RhoA and RhoC activation in response
      to LPA and EGF stimulation. Notably, the geranylgeraniol analog AFOH was more
      potent than AGOH in inhibiting RhoA and RhoC activation and invasive growth.
      Interestingly, neither AGOH nor AFOH impacted 3D growth of MCF10A cells.
      Collectively, this study demonstrates that AGOH and AFOH dramatically inhibit
      breast cancer invasion, at least in part by blocking Rho function, thus,
      suggesting that targeting prenylation by using PFIs may offer a promising
      mechanism for treatment of invasive breast cancer. 

PMID- 24587106
TI  - The anti-tumor activity of a neutralizing nanobody targeting leptin receptor in a
      mouse model of melanoma.
AB  - Environmental and genetic activation of a brain-adipocyte axis inhibits cancer
      progression. Leptin is the primary peripheral mediator of this anticancer effect
      in a mouse model of melanoma. In this study we assessed the effect of a leptin
      receptor antagonist on melanoma progression. Local administration of a
      neutralizing nanobody targeting the leptin receptor at low dose adjacent to tumor
      decreased tumor mass with no effects on body weight or food intake. In contrast,
      systemic administration of the nanobody failed to suppress tumor growth. Daily
      intraperitoneal injection of high-dose nanobody led to weight gain, hyperphagia,
      increased adiposity, hyperleptinemia, and hyperinsulinemia, and central effects
      mimicking leptin deficiency. The blockade of central actions of leptin by
      systemic delivery of nanobody may compromise its anticancer effect, underscoring
      the need to develop peripherally acting leptin antagonists coupled with efficient
      cancer-targeting delivery. 

PMID- 24587107
TI  - Co-circulation of multiple hemorrhagic fever diseases with distinct clinical
      characteristics in Dandong, China.
AB  - Hemorrhagic fevers (HF) caused by viruses and bacteria are a major public health
      problem in China and characterized by variable clinical manifestations, such that
      it is often difficult to achieve accurate diagnosis and treatment. The causes of
      HF in 85 patients admitted to Dandong hospital, China, between 2011-2012 were
      determined by serological and PCR tests. Of these, 34 patients were diagnosed
      with Huaiyangshan hemorrhagic fever (HYSHF), 34 with Hemorrhagic Fever with Renal
      Syndrome (HFRS), one with murine typhus, and one with scrub typhus. Etiologic
      agents could not be determined in the 15 remaining patients. Phylogenetic
      analyses of recovered bacterial and viral sequences revealed that the causative
      infectious agents were closely related to those described in other geographical
      regions. As these diseases have no distinctive clinical features in their early
      stage, only 13 patients were initially accurately diagnosed. The distinctive
      clinical features of HFRS and HYSHF developed during disease progression.
      Enlarged lymph nodes, cough, sputum, and diarrhea were more common in HYSHF
      patients, while more HFRS cases presented with headache, sore throat, oliguria,
      percussion pain kidney area, and petechiae. Additionally, HYSHF patients
      displayed significantly lower levels of white blood cells (WBC), higher levels of
      creations kinase (CK) and alanine aminotransferase (ALT), while HFRS patients
      presented with an elevation of blood urea nitrogen (BUN) and creatinine (CREA).
      These clinical features will assist in the accurate diagnosis of both HYSHF and
      HFRS. Overall, our data reveal the complexity of pathogens causing HFs in a
      single Chinese hospital, and highlight the need for accurate early diagnosis and
      a better understanding of their distinctive clinical features. 

PMID- 24587108
TI  - Cross-presentation of synthetic long peptides by human dendritic cells: a process
      dependent on ERAD component p97/VCP but Not sec61 and/or Derlin-1.
AB  - Antitumor vaccination using synthetic long peptides (SLP) is an additional
      therapeutic strategy currently under development. It aims to activate tumor
      specific CD8(+) CTL by professional APCs such as DCs. DCs can activate T
      lymphocytes by MHC class I presentation of exogenous antigens - a process
      referred to as "cross-presentation". Until recently, the intracellular mechanisms
      involved in cross-presentation of soluble antigens have been unclear. Here, we
      characterize the cross-presentation pathway of SLP Melan-A16-40 containing the
      HLA-A2-restricted epitope26-35 (A27L) in human DCs. Using confocal microscopy and
      specific inhibitors, we show that SLP16-40 is rapidly taken up by DC and follows
      a classical TAP- and proteasome-dependent cross-presentation pathway. Our data
      support a role for the ER-associated degradation machinery (ERAD)-related protein
      p97/VCP in the transport of SLP16-40 from early endosomes to the cytoplasm but
      formally exclude both sec61 and Derlin-1 as possible retro-translocation channels
      for cross-presentation. In addition, we show that generation of the Melan-A26-35
      peptide from the SLP16-40 was absolutely not influenced by the proteasome subunit
      composition in DC. Altogether, our findings propose a model for cross
      presentation of SLP which tends to enlarge the repertoire of potential candidates
      for retro-translocation of exogenous antigens to the cytosol. 

PMID- 24587110
TI  - Effectiveness of treatment approaches for children and adolescents with reading
      disabilities: a meta-analysis of randomized controlled trials.
AB  - Children and adolescents with reading disabilities experience a significant
      impairment in the acquisition of reading and spelling skills. Given the emotional
      and academic consequences for children with persistent reading disorders,
      evidence-based interventions are critically needed. The present meta-analysis
      extracts the results of all available randomized controlled trials. The aims were
      to determine the effectiveness of different treatment approaches and the impact
      of various factors on the efficacy of interventions. The literature search for
      published randomized-controlled trials comprised an electronic search in the
      databases ERIC, PsycINFO, PubMed, and Cochrane, and an examination of
      bibliographical references. To check for unpublished trials, we searched the
      websites clinicaltrials.com and ProQuest, and contacted experts in the field.
      Twenty-two randomized controlled trials with a total of 49 comparisons of
      experimental and control groups could be included. The comparisons evaluated five
      reading fluency trainings, three phonemic awareness instructions, three reading
      comprehension trainings, 29 phonics instructions, three auditory trainings, two
      medical treatments, and four interventions with coloured overlays or lenses. One
      trial evaluated the effectiveness of sunflower therapy and another investigated
      the effectiveness of motor exercises. The results revealed that phonics
      instruction is not only the most frequently investigated treatment approach, but
      also the only approach whose efficacy on reading and spelling performance in
      children and adolescents with reading disabilities is statistically confirmed.
      The mean effect sizes of the remaining treatment approaches did not reach
      statistical significance. The present meta-analysis demonstrates that severe
      reading and spelling difficulties can be ameliorated with appropriate treatment.
      In order to be better able to provide evidence-based interventions to children
      and adolescent with reading disabilities, research should intensify the
      application of blinded randomized controlled trials. 

PMID- 24587109
TI  - Progressive brain damage, synaptic reorganization and NMDA activation in a model
      of epileptogenic cortical dysplasia.
AB  - Whether severe epilepsy could be a progressive disorder remains as yet
      unresolved. We previously demonstrated in a rat model of acquired focal cortical
      dysplasia, the methylazoxymethanol/pilocarpine - MAM/pilocarpine - rats, that the
      occurrence of status epilepticus (SE) and subsequent seizures fostered a
      pathologic process capable of modifying the morphology of cortical pyramidal
      neurons and NMDA receptor expression/localization. We have here extended our
      analysis by evaluating neocortical and hippocampal changes in MAM/pilocarpine
      rats at different epilepsy stages, from few days after onset up to six months of
      chronic epilepsy. Our findings indicate that the process triggered by SE and
      subsequent seizures in the malformed brain i) is steadily progressive, deeply
      altering neocortical and hippocampal morphology, with atrophy of neocortex and CA
      regions and progressive increase of granule cell layer dispersion; ii) changes
      dramatically the fine morphology of neurons in neocortex and hippocampus, by
      increasing cell size and decreasing both dendrite arborization and spine density;
      iii) induces reorganization of glutamatergic and GABAergic networks in both
      neocortex and hippocampus, favoring excitatory vs inhibitory input; iv) activates
      NMDA regulatory subunits. Taken together, our data indicate that, at least in
      experimental models of brain malformations, severe seizure activity, i.e., SE
      plus recurrent seizures, may lead to a widespread, steadily progressive
      architectural, neuronal and synaptic reorganization in the brain. They also
      suggest the mechanistic relevance of glutamate/NMDA hyper-activation in the
      seizure-related brain pathologic plasticity. 

PMID- 24587111
TI  - RNA aptamer probes as optical imaging agents for the detection of amyloid
      plaques.
AB  - Optical imaging using multiphoton microscopy and whole body near infrared imaging
      has become a routine part of biomedical research. However, optical imaging
      methods rely on the availability of either small molecule reporters or
      genetically encoded fluorescent proteins, which are challenging and time
      consuming to develop. While directly labeled antibodies can also be used as
      imaging agents, antibodies are species specific, can typically not be tagged with
      multiple fluorescent reporters without interfering with target binding, and are
      bioactive, almost always eliciting a biological response and thereby influencing
      the process that is being studied. We examined the possibility of developing
      highly specific and sensitive optical imaging agents using aptamer technology. We
      developed a fluorescently tagged anti-Abeta RNA aptamer, beta55, which binds
      amyloid plaques in both ex vivo human Alzheimer's disease brain tissue and in
      vivo APP/PS1 transgenic mice. Diffuse beta55 positive halos, attributed to
      oligomeric Abeta, were observed surrounding the methoxy-XO4 positive plaque
      cores. Dot blots of synthetic Abeta aggregates provide further evidence that
      beta55 binds both fibrillar and non-fibrillar Abeta. The high binding affinity,
      the ease of probe development, and the ability to incorporate multiple and
      multimodal imaging reporters suggest that RNA aptamers may have complementary and
      perhaps advantageous properties compared to conventional optical imaging probes
      and reporters. 

PMID- 24587112
TI  - Autonomous device for application in late-phase hemorrhagic shock prevention.
AB  - Hemorrhagic shock (HS) is the leading cause of death for people with traumatic
      injuries. The onset of HS is correlated with marked changes in the plasma
      vasopressin levels and some studies indicate that administrating vasopressin in
      the bloodstream can help stabilize the situation. This situation calls naturally
      for the use of implantable devices for both the monitoring and treatment of HS.
      In this work, we present a self-powered hemorrhagic-shock autonomous integrated
      device (hemoAID) that continuously monitors vasopressin levels and releases
      vasopressin automatically when levels drop below a certain threshold. We
      demonstrate that the device can operate at physiological concentrations of
      vasopressin, in sheep serum, thus paving the way towards the development of an
      autonomous implantable device for HS prevention. 

PMID- 24587113
TI  - Combining transcranial direct current stimulation and tailor-made notched music
      training to decrease tinnitus-related distress--a pilot study.
AB  - The central auditory system has a crucial role in tinnitus generation and
      maintenance. Curative treatments for tinnitus do not yet exist. However, recent
      attempts in the therapeutic application of both acoustic stimulation/training
      procedures and electric/magnetic brain stimulation techniques have yielded
      promising results. Here, for the first time we combined tailor-made notched music
      training (TMNMT) with transcranial direct current stimulation (tDCS) in an effort
      to modulate TMNMT efficacy in the treatment of 32 patients with tonal tinnitus
      and without severe hearing loss. TMNMT is characterized by regular listening to
      so-called notched music, which is generated by digitally removing the frequency
      band of one octave width centered at the individual tinnitus frequency. TMNMT was
      applied for 10 subsequent days (2.5 hours of daily treatment). During the initial
      5 days of treatment and the initial 30 minutes of TMNMT sessions, tDCS (current
      strength: 2 mA; anodal (N = 10) vs. cathodal (N = 11) vs. sham (N = 11) groups)
      was applied simultaneously. The active electrode was placed on the head surface
      over left auditory cortex; the reference electrode was put over right supra
      orbital cortex. To evaluate treatment outcome, tinnitus-related distress and
      perceived tinnitus loudness were assessed using standardized tinnitus
      questionnaires and a visual analogue scale. The results showed a significant
      treatment effect reflected in the Tinnitus Handicap Questionnaire that was
      largest after 5 days of treatment. This effect remained significant at the end of
      follow-up 31 days after treatment cessation. Crucially, tDCS did not
      significantly modulate treatment efficacy--it did not make a difference whether
      anodal, cathodal, or sham tDCS was applied. Possible explanations for the
      findings and functional modifications of the experimental design for future
      studies (e.g. the selection of control conditions) are discussed.

PMID- 24587114
TI  - Whole body vibration training--improving balance control and muscle endurance.
AB  - Exercise combined with whole body vibration (WBV) is becoming increasingly
      popular, although additional effects of WBV in comparison to conventional
      exercises are still discussed controversially in literature. Heterogeneous
      findings are attributed to large differences in the training designs between WBV
      and "control" groups in regard to training volume, load and type. In order to
      separate the additional effects of WBV from the overall adaptations due to the
      intervention, in this study, a four-week WBV training setup was compared to a
      matched intervention program with identical training parameters in both training
      settings except for the exposure to WBV. In a repeated-measures matched-subject
      design, 38 participants were assigned to either the WBV group (VIB) or the
      equivalent training group (CON). Training duration, number of sets, rest periods
      and task-specific instructions were matched between the groups. Balance, jump
      height and local static muscle endurance were assessed before and after the
      training period. The statistical analysis revealed significant interaction
      effects of group*time for balance and local static muscle endurance (p<0.05).
      Hence, WBV caused an additional effect on balance control (pre vs. post VIB +13%,
      p<0.05 and CON +6%, p = 0.33) and local static muscle endurance (pre vs. post VIB
      +36%, p<0.05 and CON +11%, p = 0.49). The effect on jump height remained
      insignificant (pre vs. post VIB +3%, p = 0.25 and CON +/-0%, p = 0.82). This
      study provides evidence for the additional effects of WBV above conventional
      exercise alone. As far as balance and muscle endurance of the lower leg are
      concerned, a training program that includes WBV can provide supplementary
      benefits in young and well-trained adults compared to an equivalent program that
      does not include WBV. 

PMID- 24587115
TI  - Common variants in CYP2R1 and GC genes predict vitamin D concentrations in
      healthy Danish children and adults.
AB  - Environmental factors such as diet, intake of vitamin D supplements and exposure
      to sunlight are known to influence serum vitamin D concentrations. Genetic
      epidemiology of vitamin D is in its infancy and a better understanding on how
      genetic variation influences vitamin D concentration is needed. We aimed to
      analyse previously reported vitamin D-related polymorphisms in relation to serum
      25(OH)D concentrations in 201 healthy Danish families with dependent children in
      late summer in Denmark. Serum 25(OH)D concentrations and a total of 25 SNPs in
      GC, VDR, CYP2R1, CYP24A1, CYP27B1, C10or88 and DHCR7/NADSYN1 genes were analysed
      in 758 participants. Genotype distributions were in Hardy-Weinberg equilibrium
      for the adult population for all the studied polymorphisms. Four SNPs in CYP2R1
      (rs1562902, rs7116978, rs10741657 and rs10766197) and six SNPs in GC (rs4588,
      rs842999, rs2282679, rs12512631, rs16846876 and rs17467825) were statistically
      significantly associated with serum 25(OH)D concentrations in children, adults
      and all combined. Several of the SNPs were in strong linkage disequilibrium, and
      the associations were driven by CYP2R1-rs10741657 and rs10766197, and by GC
      rs4588 and rs842999. Genetic risk score analysis showed that carriers with no
      risk alleles of CYP2R1-rs10741657 and rs10766197, and/or GC rs4588 and rs842999
      had significantly higher serum 25(OH)D concentrations compared to carriers of all
      risk alleles. To conclude, our results provide supporting evidence that common
      polymorphisms in GC and CYP2R1 are associated with serum 25(OH)D concentrations
      in the Caucasian population and that certain haplotypes may predispose to lower
      25(OH)D concentrations in late summer in Denmark. 

PMID- 24587116
TI  - A novel dried blood spot-LCMS method for the quantification of methotrexate
      polyglutamates as a potential marker for methotrexate use in children.
AB  - OBJECTIVE: Development and validation of a selective and sensitive LCMS method
      for the determination of methotrexate polyglutamates in dried blood spots (DBS).
      METHODS: DBS samples [spiked or patient samples] were prepared by applying blood
      to Guthrie cards which was then dried at room temperature. The method utilised 6
      mm disks punched from the DBS samples (equivalent to approximately 12 ul of whole
      blood). The simple treatment procedure was based on protein precipitation using
      perchloric acid followed by solid phase extraction using MAX cartridges. The
      extracted sample was chromatographed using a reversed phase system involving an
      Atlantis T3-C18 column (3 um, 2.1 * 150 mm) preceded by Atlantis guard column of
      matching chemistry. Analytes were subjected to LCMS analysis using positive
      electrospray ionization. KEY RESULTS: The method was linear over the range 5-400
      nmol/L. The limits of detection and quantification were 1.6 and 5 nmol/L for
      individual polyglutamates and 1.5 and 4.5 nmol/L for total polyglutamates,
      respectively. The method has been applied successfully to the determination of
      DBS finger-prick samples from 47 paediatric patients and results confirmed with
      concentrations measured in matched RBC samples using conventional HPLC-UV
      technique. CONCLUSIONS AND CLINICAL RELEVANCE: The methodology has a potential
      for application in a range of clinical studies (e.g. pharmacokinetic evaluations
      or medication adherence assessment) since it is minimally invasive and easy to
      perform, potentially allowing parents to take blood samples at home. The
      feasibility of using DBS sampling can be of major value for future clinical
      trials or clinical care in paediatric rheumatology.

PMID- 24587117
TI  - Origin and loss of nested LRRTM/alpha-catenin genes during vertebrate evolution.
AB  - Leucine-rich repeat transmembrane neuronal proteins (LRRTMs) form in mammals a
      family of four postsynaptic adhesion proteins, which have been shown to bind
      neurexins and heparan sulphate proteoglycan (HSPG) glypican on the presynaptic
      side. Mutations in the genes encoding LRRTMs and neurexins are implicated in
      human cognitive disorders such as schizophrenia and autism. Our analysis shows
      that in most jawed vertebrates, lrrtm1, lrrtm2, and lrrtm3 genes are nested on
      opposite strands of large conserved intron of alpha-catenin genes ctnna2, ctnna1,
      and ctnna3, respectively. No lrrtm genes could be found in tunicates or
      lancelets, while two lrrtm genes are found in the lamprey genome, one of which is
      adjacent to a single ctnna homolog. Based on similar highly positive net charge
      of lamprey LRRTMs and the HSPG-binding LRRTM3 and LRRTM4 proteins, we speculate
      that the ancestral LRRTM might have bound HSPG before acquiring neurexins as
      binding partners. Our model suggests that lrrtm gene translocated into the large
      ctnna intron in early vertebrates, and that subsequent duplications resulted in
      three lrrtm/ctnna gene pairs present in most jawed vertebrates. However, we
      detected three prominent exceptions: (1) the lrrtm3/ctnna3 gene structure is
      absent in the ray-finned fish genomes, (2) the genomes of clawed frogs contain
      ctnna1 but lack the corresponding nested (lrrtm2) gene, and (3) contain lrrtm3
      gene in the syntenic position but lack the corresponding host (ctnna3) gene. We
      identified several other protein-coding nested gene structures of which either
      the host or the nested gene has presumably been lost in the frog or chicken
      lineages. Interestingly, majority of these nested genes comprise LRR domains. 

PMID- 24587118
TI  - Using stochastic gradient boosting to infer stopover habitat selection and
      distribution of Hooded Cranes Grus monacha during spring migration in Lindian,
      Northeast China.
AB  - The Hooded Crane (Grus monacha) is a globally vulnerable species, and habitat
      loss is the primary cause of its decline. To date, little is known regarding the
      specific habitat needs, and stopover habitat selection in particular, of the
      Hooded Crane. In this study we used stochastic gradient boosting (TreeNet) to
      develop three specific habitat selection models for roosting, daytime resting,
      and feeding site selection. In addition, we used a geographic information system
      (GIS) combined with TreeNet to develop a species distribution model. We also
      generated a digital map of the relative occurrence index (ROI) of this species at
      daytime resting sites in the study area. Our study indicated that the water
      depth, distance to village, coverage of deciduous leaves, open water area, and
      density of plants were the major predictors of roosting site selection. For
      daytime resting site selection, the distance to wetland, distance to farmland,
      and distance to road were the primary predictors. For feeding site selection, the
      distance to road, quantity of food, plant coverage, distance to village, plant
      density, distance to wetland, and distance to river were contributing factors,
      and the distance to road and quantity of food were the most important predictors.
      The predictive map showed that there were two consistent multi-year daytime
      resting sites in our study area. Our field work in 2013 using systematic ground
      truthing confirmed that this prediction was accurate. Based on this study, we
      suggest that Lindian plays an important role for migratory birds and that
      cultivation practices should be adjusted locally. Furthermore, public education
      programs to promote the concept of the harmonious coexistence of humans and
      cranes can help successfully protect this species in the long term and eventually
      lead to its delisting by the IUCN. 

PMID- 24587119
TI  - Achilles' ear? Inferior human short-term and recognition memory in the auditory
      modality.
AB  - Studies of the memory capabilities of nonhuman primates have consistently
      revealed a relative weakness for auditory compared to visual or tactile stimuli:
      extensive training is required to learn auditory memory tasks, and subjects are
      only capable of retaining acoustic information for a brief period of time.
      Whether a parallel deficit exists in human auditory memory remains an outstanding
      question. In the current study, a short-term memory paradigm was used to test
      human subjects' retention of simple auditory, visual, and tactile stimuli that
      were carefully equated in terms of discriminability, stimulus exposure time, and
      temporal dynamics. Mean accuracy did not differ significantly among sensory
      modalities at very short retention intervals (1-4 s). However, at longer
      retention intervals (8-32 s), accuracy for auditory stimuli fell substantially
      below that observed for visual and tactile stimuli. In the interest of extending
      the ecological validity of these findings, a second experiment tested recognition
      memory for complex, naturalistic stimuli that would likely be encountered in
      everyday life. Subjects were able to identify all stimuli when retention was not
      required, however, recognition accuracy following a delay period was again
      inferior for auditory compared to visual and tactile stimuli. Thus, the outcomes
      of both experiments provide a human parallel to the pattern of results observed
      in nonhuman primates. The results are interpreted in light of neuropsychological
      data from nonhuman primates, which suggest a difference in the degree to which
      auditory, visual, and tactile memory are mediated by the perirhinal and
      entorhinal cortices.

PMID- 24587120
TI  - A latent class analysis of stigmatizing attitudes and knowledge of HIV risk among
      youth in South Africa.
AB  - BACKGROUND: The current study aims to investigate how the ability to accurately
      gauge risk factors associated with contracting HIV while taking into
      consideration various individual and community level socio-demographic
      characteristics (e.g., race and poverty) predicts the nature of stigmatizing
      attitudes toward persons with HIV. METHODS: Data from a sample of 1,347 Cape Town
      area youth who participated in the Cape Area Panel Study (CAPS) Wave 2a were
      used. Latent Class Analysis was conducted to ascertain whether response patterns
      regarding knowledge of HIV contraction suggest the presence of subgroups within
      the sample. RESULTS: Findings indicate that there are four latent classes
      representing unique response pattern profiles regarding knowledge of HIV
      contraction. Additionally, our results suggest that those in South Africa who are
      classified as "white," live in more affluent communities, and have more phobic
      perceptions of HIV risk are also more likely to have the most stigmatizing
      attitudes toward those who are HIV positive. CONCLUSION: Implications of these
      findings include extending HIV knowledge, education, and awareness programs to
      those who are not traditionally targeted in an attempt to increase levels of
      knowledge about HIV and, consequently, decrease stigma.

PMID- 24587121
TI  - Differential expression of adenine nucleotide converting enzymes in mitochondrial
      intermembrane space: a potential role of adenylate kinase isozyme 2 in neutrophil
      differentiation.
AB  - Adenine nucleotide dynamics in the mitochondrial intermembrane space (IMS) play a
      key role in oxidative phosphorylation. In a previous study, Drosophila adenylate
      kinase isozyme 2 (Dak2) knockout was reported to cause developmental lethality at
      the larval stage in Drosophila melanogaster. In addition, two other studies
      reported that AK2 is a responsible gene for reticular dysgenesis (RD), a human
      disease that is characterized by severe combined immunodeficiency and deafness.
      Therefore, mitochondrial AK2 may play an important role in hematopoietic
      differentiation and ontogenesis. Three additional adenine nucleotide metabolizing
      enzymes, including mitochondrial creatine kinases (CKMT1 and CKMT2) and
      nucleoside diphosphate kinase isoform D (NDPK-D), have been found in IMS.
      Although these kinases generate ADP for ATP synthesis, their involvement in RD
      remains unclear and still an open question. In this study, mRNA and protein
      expressions of these mitochondrial kinases were firstly examined in mouse ES
      cells, day 8 embryos, and 7-week-old adult mice. It was found that their
      expressions are spatiotemporally regulated, and Ak2 is exclusively expressed in
      bone marrow, which is a major hematopoietic tissue in adults. In subsequent
      experiments, we identified increased expression of both AK2 and CKMT1 during
      macrophage differentiation and exclusive production of AK2 during neutrophil
      differentiation using HL-60 cells as an in vitro model of hematopoietic
      differentiation. Furthermore, AK2 knockdown specifically inhibited neutrophil
      differentiation without affecting macrophage differentiation. These data suggest
      that AK2 is indispensable for neutrophil differentiation and indicate a possible
      causative link between AK2 deficiency and neutropenia in RD. 

PMID- 24587122
TI  - Establishment of a bacterial infection model using the European honeybee, Apis
      mellifera L.
AB  - Injection of human pathogenic bacteria (Pseudomonas aeruginosa, Serratia
      marcescens, Salmonella enterica, Staphylococcus aureus, and Listeria
      monocytogenes) into the hemocoel of honeybee (Apis mellifera L.) workers kills
      the infected bees. The bee-killing effects of the pathogens were affected by
      temperature, and the LD50 values at 37 degrees C were more than 100-fold lower
      than those at 15 degrees C. Gene-disrupted S. aureus mutants of virulence genes
      such as agrA, saeS, arlR, srtA, hla, and hlb had attenuated bee-killing ability.
      Nurse bees were less susceptible than foragers and drones to S. aureus infection.
      Injection of antibiotics clinically used for humans had therapeutic effects
      against S. aureus infections of bees, and the ED50 values of these antibiotics
      were comparable with those determined in mammalian models. Moreover, the
      effectiveness of orally administered antibiotics was consistent between honeybees
      and mammals. These findings suggest that the honeybee could be a useful model for
      assessing the pathogenesis of human-infecting bacteria and the effectiveness of
      antibiotics.

PMID- 24587123
TI  - Real-time measurements of the redox states of c-type cytochromes in electroactive
      biofilms: a confocal resonance Raman Microscopy study.
AB  - Confocal Resonance Raman Microscopy (CRRM) was used to probe variations of redox
      state of c-type cytochromes embedded in living mixed-culture electroactive
      biofilms exposed to different electrode polarizations, under potentiostatic and
      potentiodynamic conditions. In the absence of the metabolic substrate acetate,
      the redox state of cytochromes followed the application of reducing and oxidizing
      electrode potentials. Real-time monitoring of the redox state of cytochromes
      during cyclic voltammetry (CV) in a potential window where cytochromes reduction
      occurs, evidenced a measurable time delay between the oxidation of redox
      cofactors probed by CV at the electrode interface, and oxidation of distal
      cytochromes probed by CRRM. This delay was used to tentatively estimate the
      diffusivity of electrons through the biofilm. In the presence of acetate, the
      resonance Raman spectra of young (10 days, j = 208 +/- 49 uA cm(-2)) and mature
      (57 days, j = 267 +/- 73 uA cm(-2)) biofilms show that cytochromes remained
      oxidized homogeneously even at layers as far as 70 um from the electrode,
      implying the existence of slow metabolic kinetics that do not result in the
      formation of a redox gradient inside the biofilm during anode respiration.
      However, old biofilms (80 days, j = 190 +/- 37 uA cm(-2)) with thickness above
      100 um were characterized by reduced catalytic activity compared to the previous
      developing stages. The cytochromes in these biofilm were mainly in the reduced
      redox state, showing that only aged mixed-culture biofilms accumulate electrons
      during anode respiration. These results differ substantially from recent
      observations in pure Geobacter sulfurreducens electroactive biofilms, in which
      accumulation of reduced cytochromes is already observed in thinner biofilms, thus
      suggesting different bottlenecks in current production for mixed-culture and G.
      sulfurreducens biofilms.

PMID- 24587124
TI  - Murine model for Fusarium oxysporum invasive fusariosis reveals organ-specific
      structures for dissemination and long-term persistence.
AB  - The soil-borne plant pathogen Fusarium oxysporum causes life-threatening invasive
      fusariosis in immunocompromised individuals. The mechanism of infection in
      mammalian hosts is largely unknown. In the present study we show that the
      symptoms of disseminated fusariosis caused by F. oxysporum in immunosuppressed
      mice are remarkably similar to those reported in humans. Distinct fungal
      structures were observed inside the host, depending on the infected organ.
      Invasive hyphae developed in the heart and kidney, causing massive colonization
      of the organs. By contrast, chlamydospore-like survival structures were found in
      lung, spleen and liver. Systemically infected mice also developed skin and eye
      infections, as well as thrombosis and necrosis in the tail. We further show that
      F. oxysporum can disseminate and persist in the organs of immunocompetent
      animals, and that these latent infections can lead to lethal systemic fusariosis
      if the host is later subjected to immunosuppressive treatment. 

PMID- 24587125
TI  - Genotypic analysis of meningococcal factor h-binding protein from non-culture
      clinical specimens.
AB  - Factor H-Binding Protein (fHbp) is an outer membrane protein antigen included in
      two novel meningococcal group B vaccines and, as such, is an important typing
      target. Approximately 50% of meningococcal disease cases in England and Wales are
      confirmed using real-time PCR on non-culture clinical specimens only. Protocols
      for typing fHbp from this subset of cases have not yet been established. Here we
      present a nested PCR-based assay designed to amplify and sequence fHbp from non
      culture clinical specimens. From analytical sensitivity experiments carried out
      using diluted DNA extracts, an estimated analytical sensitivity limit of 6 fg/uL
      of DNA (<3 genome copies/uL) was calculated. The sensitivity of the assay was
      shown to be comparable to the ctrA-directed real-time PCR assay currently used to
      confirm invasive disease diagnoses from submitted clinical specimens. A panel of
      96 diverse, patient-matched clinical specimen/isolate pairs from invasive disease
      cases was used to illustrate the breadth of strain coverage for the assay. All
      fHbp alleles sequenced from the isolates matched those derived from previous
      whole genome analyses. The first-round PCR primer binding sites are highly
      conserved, however an exceptional second-round PCR primer site mismatch in one
      validation isolate prevented amplification. In this case, amplification from the
      corresponding clinical specimen was achieved, suggesting that the use of a nested
      PCR procedure may compensate for any minor mismatches in round-two primer sites.
      The assay was successful at typing 91/96 (94.8%) of the non-culture clinical
      specimens in this study and exhibits sufficient sensitivity to type fHbp from the
      vast majority of non-culture clinical specimens received by the Meningococcal
      Reference Unit, Public Health England. 

PMID- 24587126
TI  - Cultivation-independent screening revealed hot spots of IncP-1, IncP-7 and IncP-9
      plasmid occurrence in different environmental habitats.
AB  - IncP-1, IncP-7 and IncP-9 plasmids often carry genes encoding enzymes involved in
      the degradation of man-made and natural contaminants, thus contributing to
      bacterial survival in polluted environments. However, the lack of suitable
      molecular tools often limits the detection of these plasmids in the environment.
      In this study, PCR followed by Southern blot hybridization detected the presence
      of plasmid-specific sequences in total community (TC-) DNA or fosmid DNA from
      samples originating from different environments and geographic regions. A novel
      primer system targeting IncP-9 plasmids was developed and applied along with
      established primers for IncP-1 and IncP-7. Screening TC-DNA from biopurification
      systems (BPS) which are used on farms for the purification of pesticide
      contaminated water revealed high abundances of IncP-1 plasmids belonging to
      different subgroups as well as IncP-7 and IncP-9. The novel IncP-9 primer-system
      targeting the rep gene of nine IncP-9 subgroups allowed the detection of a high
      diversity of IncP-9 plasmid specific sequences in environments with different
      sources of pollution. Thus polluted sites are "hot spots" of plasmids potentially
      carrying catabolic genes. 

PMID- 24587127
TI  - Body mass index and risk of age-related cataract: a meta-analysis of prospective
      cohort studies.
AB  - BACKGROUND: Age-related cataract (ARC) is the leading cause of blindness in the
      world. The relationship between body mass index (BMI) and risk of ARC is
      controversial across observational studies. We therefore performed this meta
      analysis to evaluate the association between BMI and risk of ARC. METHODS:
      Eligible studies were identified through an electronic search of PubMed, Embase
      and the Cochrane Library. We pooled study-specific relative risks (RRs) and 95%
      confidence intervals (CIs) to determine the risk of ARC associated with BMI
      categories and per 1 kg/m2 increase in BMI. RESULTS: A total of 17 prospective
      cohort studies were included in the meta-analysis. The pooled RRs of ARC were
      1.08 (95% CI, 1.01-1.16) for overweight and 1.19 (95% CI, 1.10-1.28) for obesity
      compared with normal weight. These findings were robust when stratified by sex,
      sample source, outcome types and confounders, while significantly differed by
      assessment of BMI and ARC, and duration of follow-up. The summary RR suggested
      that per 1 kg/m2 increase in BMI was associated with a 2% increased risk of ARC
      (RR 1.02, 95% CI 1.01-1.03). Pooled estimates of RRs consistently indicated a
      trend for subjects with a high BMI to develop posterior subcapsular cataracts (RR
      1.19, 95% CI 1.06-1.35, for overweight; RR 1.50, 95% CI 1.24-1.81, for obesity;
      RR 1.04, 95% CI 1.01-1.06, per 1 kg/m2 increase in BMI) other than nuclear or
      cortical cataracts. CONCLUSIONS: The overall findings suggest that elevated BMI
      may increase the risk of ARC, especially posterior subcapsular cataracts. Further
      trials are needed to investigate the effect of weight reduction in obese
      populations on the risk of ARC.

PMID- 24587128
TI  - Identification of a 251 gene expression signature that can accurately detect M.
      tuberculosis in patients with and without HIV co-infection.
AB  - BACKGROUND: Co-infection with tuberculosis (TB) is the leading cause of death in
      HIV-infected individuals. However, diagnosis of TB, especially in the presence of
      an HIV co-infection, can be limiting due to the high inaccuracy associated with
      the use of conventional diagnostic methods. Here we report a gene signature that
      can identify a tuberculosis infection in patients co-infected with HIV as well as
      in the absence of HIV. METHODS: We analyzed global gene expression data from
      peripheral blood mononuclear cell (PBMC) samples of patients that were either
      mono-infected with HIV or co-infected with HIV/TB and used support vector
      machines to identify a gene signature that can distinguish between the two
      classes. We then validated our results using publically available gene expression
      data from patients mono-infected with TB. RESULTS: Our analysis successfully
      identified a 251-gene signature that accurately distinguishes patients co
      infected with HIV/TB from those infected with HIV only, with an overall accuracy
      of 81.4% (sensitivity = 76.2%, specificity = 86.4%). Furthermore, we show that
      our 251-gene signature can also accurately distinguish patients with active TB in
      the absence of an HIV infection from both patients with a latent TB infection and
      healthy controls (88.9-94.7% accuracy; 69.2-90% sensitivity and 90.3-100%
      specificity). We also demonstrate that the expression levels of the 251-gene
      signature diminish as a correlate of the length of TB treatment. CONCLUSIONS: A
      251-gene signature is described to (a) detect TB in the presence or absence of an
      HIV co-infection, and (b) assess response to treatment following anti-TB therapy.

PMID- 24587129
TI  - Two pear glutathione S-transferases genes are regulated during fruit development
      and involved in response to salicylic acid, auxin, and glucose signaling.
AB  - Two genes encoding putative glutathione S-transferase proteins were isolated from
      pear (Pyrus pyrifolia) and designated PpGST1 and PpGST2. The deduced PpGST1 and
      PpGST2 proteins contain conserved Glutathione S-transferase N-terminal domain
      (GST_N) and Glutathione S-transferase, C-terminal domain (GST_C). Using PCR
      amplification technique, the genomic clones corresponding to PpGST1 and PpGST2
      were isolated and shown to contain two introns and a singal intron respectively
      with typical GT/AG boundaries defining the splice junctions. Phylogenetic
      analysis clearly demonstrated that PpGST1 belonged to Phi class of GST
      superfamilies and had high homology with apple MdGST, while PpGST2 was classified
      into the Tau class of GST superfamilies. The expression of PpGST1 and PpGST2
      genes was developmentally regulated in fruit. Further study demonstrated that
      PpGST1 and PpGST2 expression was remarkably induced by glucose, salicylic acid
      (SA) and indole-3-aceticacid (IAA) treatments in pear fruit, and in diseased
      fruit. These data suggested that PpGST1 and PpGST2 might be involved in response
      to sugar, SA, and IAA signaling during fruit development of pear. 

PMID- 24587130
TI  - Circulating angiogenic cell dysfunction in patients with hereditary hemorrhagic
      telangiectasia.
AB  - Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant vascular
      disorder. Circulating angiogenic cells (CACs) play an important role in vascular
      repair and regeneration. This study was designed to examine the function of CACs
      derived from patients with HHT. Peripheral blood mononuclear cells (PBMNCs)
      isolated from patients with HHT and age- and gender-matched healthy volunteers
      were assessed for expression of CD34, CD133 and VEGF receptor 2 by flow
      cytometry. PBMNCs were cultured to procure early outgrowth CACs. Development of
      endothelial cell (EC) phenotype in CACs was analyzed by fluorescence microscopy.
      CAC apoptosis was assayed with Annexin V staining, and CAC migration assessed by
      a modified Boyden chamber assay. mRNA expression of endoglin (ENG), activin
      receptor-like kinase-1 (ACVLR1 or ALK1) and endothelial nitric oxide synthase
      (eNOS) in CACs was measured by real time RT-PCR. The percentage of CD34+ cells in
      PBMNCs from HHT patients was significantly higher than in PBMNCs of healthy
      controls. CACs derived from patients with HHT not only showed a significant
      reduction in EC-selective surface markers following 7-day culture, but also a
      significant increase in the rate of basal apoptosis and blunted migration in
      response to vascular endothelial growth factor and stromal cell-derived factor-1.
      CACs from HHT patients expressed significantly lower levels of ENG, ALK1 and eNOS
      mRNAs. In conclusion, CACs from patients with HHT exhibited various functional
      impairments, suggesting a reduced regenerative capacity of CACs to repair the
      vascular lesions seen in HHT patients. 

PMID- 24587131
TI  - Cardiac function and architecture are maintained in a model of cardiorestricted
      overexpression of the prorenin-renin receptor.
AB  - The (pro)renin-renin receptor, (P)RR has been claimed to be a novel element of
      the renin-angiotensin system (RAS). The function of (P)RR has been widely studied
      in renal and vascular pathology but the cardio-specific function of (P)RR has not
      been studied in detail. We therefore generated a transgenic mouse (Tg) with
      cardio-restricted (P)RR overexpression driven by the alpha-MHC promotor. The mRNA
      expression of (P)RR was ~ 170-fold higher (P<0.001) and protein expression ~ 5
      fold higher (P<0.001) in hearts of Tg mice as compared to non-transgenic (wild
      type, Wt) littermates. This level of overexpression was not associated with
      spontaneous cardiac morphological or functional abnormalities in Tg mice. To
      assess whether (P)RR could play a role in cardiac hypertrophy, we infused ISO for
      28 days, but this caused an equal degree of cardiac hypertrophy and fibrosis in
      Wt and Tg mice. In addition, ischemia-reperfusion injury was performed in
      Langendorff perfused isolated mouse hearts. We did not observe differences in
      parameters of cardiac function or damage between Wt and Tg mouse hearts under
      these conditions. Finally, we explored whether the hypoxia sensing response would
      be modulated by (P)RR using HeLa cells with and without (P)RR overexpression. We
      did not establish any effect of (P)RR on expression of genes associated with the
      hypoxic response. These results demonstrate that cardio-specific overexpression
      of (P)RR does not provoke phenotypical differences in the heart, and does not
      affect the hearts' response to stress and injury. It is concluded that increased
      myocardial (P)RR expression is unlikely to have a major role in pathological
      cardiac remodeling.

PMID- 24587132
TI  - MicroRNA gene polymorphisms and environmental factors increase patient
      susceptibility to hepatocellular carcinoma.
AB  - BACKGROUND: Micro RNAs (miRNAs) are small RNA fragments that naturally exist in
      the human body. Through various physiological mechanisms, miRNAs can generate
      different functions for regulating RNA protein levels and balancing
      abnormalities. Abnormal miRNA expression has been reported to be highly related
      to several diseases and cancers. Single-nucleotide polymorphisms (SNPs) in miRNAs
      have been reported to increase patient susceptibility and affect patient
      prognosis and survival. We adopted a case-control research design to verify the
      relationship between miRNAs and hepatocellular carcinoma. METHODOLOGY/PRINCIPAL
      FINDINGS: A total of 525 subjects, including 377 controls and 188 hepatocellular
      carcinoma patients, were selected. Polymerase chain reaction-restriction fragment
      length polymorphism (PCR-RFLP) and real-time PCR were used to analyze miRNA146a
      (rs2910164), miRNA149 (rs2292832), miRNA196 (rs11614913), and miRNA499
      (rs3746444) genetic polymorphisms between the control group and the case group.
      The results indicate that people who carry the rs3746444 CT or CC genotypes may
      have a significantly increased susceptibility to hepatocellular carcinoma
      (adjusted odds ratio [AOR] = 2.84, 95% confidence interval [CI] = 1.88-4.30). In
      addition, when combined with environmental risk factors, such as smoking and
      alcohol consumption, interaction effects were observed between gene polymorphisms
      and environmental factors (odds ratio [OR] = 4.69, 95% CI = 2.52-8.70; AOR =
      3.38, 95% CI = 1.68-6.80). CONCLUSIONS: These results suggest that a significant
      association exists between miRNA499 SNPs and hepatocellular carcinoma. Gene
      environment interactions of miRNA499 polymorphisms, smoking, and alcohol
      consumption might alter hepatocellular carcinoma susceptibility.

PMID- 24587134
TI  - Water filtration using plant xylem.
AB  - Effective point-of-use devices for providing safe drinking water are urgently
      needed to reduce the global burden of waterborne disease. Here we show that plant
      xylem from the sapwood of coniferous trees--a readily available, inexpensive,
      biodegradable, and disposable material--can remove bacteria from water by simple
      pressure-driven filtration. Approximately 3 cm(3) of sapwood can filter water at
      the rate of several liters per day, sufficient to meet the clean drinking water
      needs of one person. The results demonstrate the potential of plant xylem to
      address the need for pathogen-free drinking water in developing countries and
      resource-limited settings.

PMID- 24587133
TI  - Comparative study of somatostatin-human serum albumin fusion proteins and natural
      somatostatin on receptor binding, internalization and activation.
AB  - Albumin fusion technology, the combination of small molecular proteins or
      peptides with human serum albumin (HSA), is an effective method for improving the
      medicinal values of natural small molecular proteins or peptides. However,
      comparative studies between HSA-fusion proteins or peptides and the parent small
      molecules in biological and molecular mechanisms are less reported. In this
      study, we examined the binding property of two novel somatostatin-HSA fusion
      proteins, (SST14)2-HSA and (SST28)2-HSA, to human SSTRs in stably expressing
      SSTR1-5 HEK 293 cells; observed the regulation of receptor internalization and
      internalized receptor recycling; and detected the receptors activation of HSA
      fusion proteins in stably expressing SSTR2- and SSTR3-EGFP cells. We showed that
      both somatostatin-HSA fusion proteins had high affinity to all five SSTRs,
      stimulated the ERK1/2 phosphorylation and persistently inhibited the accumulation
      of forskolin-stimulated cAMP in SSTR2- and SSTR3-expressing cells; but were less
      potent than the synthetic somatostatin-14 (SST-14). Our experiments also showed
      that somatostatin-HSA fusion proteins did not induce the receptors
      internalization; rather, they accelerated the recycling of the internalized
      receptors induced by SST-14 to the plasma membrane. Our results indicated that
      somatostatin-HSA fusion proteins, different from SST-14, exhibit some particular
      properties in binding, regulating, and activating somatostatin receptors. 

PMID- 24587135
TI  - Improvement in low-homology template-based modeling by employing a model
      evaluation method with focus on topology.
AB  - Many template-based modeling (TBM) methods have been developed over the recent
      years that allow for protein structure prediction and for the study of structure
      function relationships for proteins. One major problem all TBM algorithms face,
      however, is their unsatisfactory performance when proteins under consideration
      are low-homology. To improve the performance of TBM methods for such targets, a
      novel model evaluation method was developed here, and named MEFTop. Our novel
      method focuses on evaluating the topology by using two novel groups of features.
      These novel features included secondary structure element (SSE) contact
      information and 3-dimensional topology information. By combining MEFTop algorithm
      with FR-t5, a threading program developed by our group, we found that this
      modified TBM program, which was named FR-t5-M, exhibited significant improvements
      in predictive abilities for low-homology protein targets. We further showed that
      the MEFTop could be a generalized method to improve threading programs for low
      homology protein targets. The softwares (FR-t5-M and MEFTop) are available to non
      commercial users at our website: http://jianglab.ibp.ac.cn/lims/FRt5M/FRt5M.html.

PMID- 24587136
TI  - The oxidative stress responsive transcription factor Pap1 confers DNA damage
      resistance on checkpoint-deficient fission yeast cells.
AB  - Eukaryotic cells invoke mechanisms to promote survival when confronted with
      cellular stress or damage to the genome. The protein kinase Chk1 is an integral
      and conserved component of the DNA damage response pathway. Mutation or
      inhibition of Chk1 results in mitotic death when cells are exposed to DNA damage.
      Oxidative stress activates a pathway that results in nuclear accumulation of the
      bZIP transcription factor Pap1. We report the novel finding that fission yeast
      Pap1 confers resistance to drug- and non-drug-induced DNA damage even when the
      DNA damage checkpoint is compromised. Multi-copy expression of Pap1 restores
      growth to chk1-deficient cells exposed to camptothecin or hydroxyurea.
      Unexpectedly, increased Pap1 expression also promotes survival of chk1-deficient
      cells with mutations in genes encoding DNA ligase (cdc17) or DNA polymerase delta
      (cdc6), but not DNA replication initiation mutants. The ability of Pap1 to confer
      resistance to DNA damage was not specific to chk1 mutants, as it also improved
      survival of rad1- and rad9-deficient cells in the presence of CPT. To confer
      resistance to DNA damage Pap1 must localize to the nucleus and be
      transcriptionally active. 

PMID- 24587137
TI  - Novel inhibitors of mitochondrial sn-glycerol 3-phosphate dehydrogenase.
AB  - Mitochondrial sn-glycerol 3-phosphate dehydrogenase (mGPDH) is a ubiquinone
      linked enzyme in the mitochondrial inner membrane best characterized as part of
      the glycerol phosphate shuttle that transfers reducing equivalents from cytosolic
      NADH into the mitochondrial electron transport chain. Despite the widespread
      expression of mGPDH and the availability of mGPDH-null mice, the physiological
      role of this enzyme remains poorly defined in many tissues, likely because of
      compensatory pathways for cytosolic regeneration of NAD+ and mechanisms for
      glycerol phosphate metabolism. Here we describe a novel class of cell-permeant
      small-molecule inhibitors of mGPDH (iGP) discovered through small-molecule
      screening. Structure-activity analysis identified a core benzimidazole-phenyl
      succinamide structure as being essential to inhibition of mGPDH while
      modifications to the benzimidazole ring system modulated both potency and off
      target effects. Live-cell imaging provided evidence that iGPs penetrate cellular
      membranes. Two compounds (iGP-1 and iGP-5) were characterized further to
      determine potency and selectivity and found to be mixed inhibitors with IC50 and
      K(i) values between ~1-15 uM. These novel mGPDH inhibitors are unique tools to
      investigate the role of glycerol 3-phosphate metabolism in both isolated and
      intact systems.

PMID- 24587138
TI  - Anterior gradient protein-2 is a regulator of cellular adhesion in prostate
      cancer.
AB  - Anterior Gradient Protein (AGR-2) is reported to be over-expressed in many
      epithelial cancers and promotes metastasis. A clear-cut mechanism for its
      observed function(s) has not been previously identified. We found significant
      upregulation of AGR-2 expression in a bone metastatic prostate cancer cell line,
      PC3, following culturing in bone marrow-conditioned medium. Substantial AGR-2
      expression was also confirmed in prostate cancer tissue specimens in patients
      with bone lesions. By developing stable clones of PC3 cells with varying levels
      of AGR-2 expression, we identified that abrogation of AGR-2 significantly reduced
      cellular attachment to fibronectin, collagen I, collagen IV, laminin I and
      fibrinogen. Loss of cellular adhesion was associated with sharp decrease in the
      expression of alpha4, alpha5, alphaV, beta3 and beta4 integrins. Failure to
      undergo apoptosis following detachment is a hallmark of epithelial cancer
      metastasis. The AGR-2-silenced PC3 cells showed higher resistance to Tumor
      necrosis factor-related apoptosis- inducing ligand (TRAIL) induced apoptosis in
      vitro. This observation was also supported by significantly reduced Caspase-3
      expression in AGR-2-silenced PC3 cells, which is a key effector of both extrinsic
      and intrinsic death signaling pathways. These data suggest that AGR-2 influence
      prostate cancer metastasis by regulation of cellular adhesion and apoptosis. 

PMID- 24587139
TI  - From the environment to the host: re-wiring of the transcriptome of Pseudomonas
      aeruginosa from 22 degrees C to 37 degrees C.
AB  - Pseudomonas aeruginosa is a highly versatile opportunistic pathogen capable of
      colonizing multiple ecological niches. This bacterium is responsible for a wide
      range of both acute and chronic infections in a variety of hosts. The success of
      this microorganism relies on its ability to adapt to environmental changes and re
      program its regulatory and metabolic networks. The study of P. aeruginosa
      adaptation to temperature is crucial to understanding the pathogenesis upon
      infection of its mammalian host. We examined the effects of growth temperature on
      the transcriptome of the P. aeruginosa PAO1. Microarray analysis of PAO1 grown in
      Lysogeny broth at mid-exponential phase at 22 degrees C and 37 degrees C revealed
      that temperature changes are responsible for the differential transcriptional
      regulation of 6.4% of the genome. Major alterations were observed in bacterial
      metabolism, replication, and nutrient acquisition. Quorum-sensing and exoproteins
      secreted by type I, II, and III secretion systems, involved in the adaptation of
      P. aeruginosa to the mammalian host during infection, were up-regulated at 37
      degrees C compared to 22 degrees C. Genes encoding arginine degradation enzymes
      were highly up-regulated at 22 degrees C, together with the genes involved in the
      synthesis of pyoverdine. However, genes involved in pyochelin biosynthesis were
      up-regulated at 37 degrees C. We observed that the changes in expression of P.
      aeruginosa siderophores correlated to an overall increase in Fe2+ extracellular
      concentration at 37 degrees C and a peak in Fe3+ extracellular concentration at
      22 degrees C. This suggests a distinct change in iron acquisition strategies when
      the bacterium switches from the external environment to the host. Our work
      identifies global changes in bacterial metabolism and nutrient acquisition
      induced by growth at different temperatures. Overall, this study identifies
      factors that are regulated in genome-wide adaptation processes and discusses how
      this life-threatening pathogen responds to temperature.

PMID- 24587140
TI  - Metronidazole or Cotrimoxazole therapy is associated with a decrease in
      intestinal bioavailability of common antiretroviral drugs.
AB  - Metronidazole (MTZ) and Cotrimoxazole (CTX) are used in HIV/AIDS patients
      eligible for antiretroviral treatment. The objective of this animal study was to
      determine whether pre-treatment with antibiotics affects the intestinal
      bioavailability of Atazanavir (ATV) and Ritonavir (RTV). After oral
      administration of 1 mg MTZ and CTX for 7 days, the rat colonic mucosa were
      analyzed for mucus thickness or placed in Ussing chambers to measure ATV and RTV
      net transepithelial fluxes (Jnet). 1. In control rats, the mucus thickness was
      43.3+/-7.6 um and 40.7+/-6.9 um, in proximal and distal colon, respectively. In
      proximal colon, the thickness was 57.2+/-8.8 and 58.2+/-6.9 um after MTZ and CTX,
      respectively whereas in distal colon, the thickness was 121.1+/-38.4 and 170.5+/
      35.0 um (P<0.05) respectively. 2. Transepithelial conductance was reduced after
      MTZ or CTX in the proximal and distal colon. 3. In control, net ATV secretion was
      observed both in proximal (-0.36+/-0.02 ug.hr(-1) cm(-2)) and distal colon (
      0.30+/-0.08 ug.hr(-1) cm(-2)). After MTZ and CTX, it was increased in the
      proximal colon by two 2 fold and 4 fold, respectively and in the distal colon by
      3 fold and 5 fold, respectively. 4. In control, there was no net active RTV
      transport either in proximal (+0.01+/-0.01 ug.hr(-1) cm(-2)) or distal colon
      (+0.04+/-0.01 ug.hr(-1) cm(-2)). After MTZ and CTX, secretion was increased 5
      fold and 10 fold, respectively, in the proximal colon and two fold and 5 fold,
      respectively in the distal colon (p<0.001). In conclusion, after MTZ and CTX
      therapy, the mucus layer was enlarged, passive permeability was decreased and ATV
      and RTV were actively secreted by the colonic epithelium suggesting that, in rat,
      the intestinal bioavailability of ATV and RTV is impaired after antibiotic
      therapy. 

PMID- 24587141
TI  - Hospital presenting self-harm and risk of fatal and non-fatal repetition:
      systematic review and meta-analysis.
AB  - BACKGROUND: Non-fatal self-harm is one of the most frequent reasons for emergency
      hospital admission and the strongest risk factor for subsequent suicide. Repeat
      self-harm and suicide are key clinical outcomes of the hospital management of
      self-harm. We have undertaken a comprehensive review of the international
      literature on the incidence of fatal and non-fatal repeat self-harm and
      investigated factors influencing variation in these estimates as well as changes
      in the incidence of repeat self-harm and suicide over the last 30 years. METHODS
      AND FINDINGS: Medline, EMBASE, PsycINFO, Google Scholar, article reference lists
      and personal paper collections of the authors were searched for studies
      describing rates of fatal and non-fatal self-harm amongst people who presented to
      health care services for deliberate self-harm. Heterogeneity in pooled estimates
      of repeat self-harm incidence was investigated using stratified meta-analysis and
      meta-regression. The search identified 177 relevant papers. The risk of suicide
      in the 12 months after an index attempt was 1.6% (CI 1.2-2.4) and 3.9% (CI 3.2
      4.8) after 5 years. The estimated 1 year rate of non-fatal repeat self-harm was
      16.3% (CI 15.1-17.7). This proportion was considerably lower in Asian countries
      (10.0%, CI 7.3-13.6%) and varies between studies identifying repeat episodes
      using hospital admission data (13.7%, CI 12.3-15.3) and studies using patient
      report (21.9%, CI 14.3-32.2). There was no evidence that the incidence of repeat
      self-harm was lower in more recent (post 2000) studies compared to those from the
      1980s and 1990s. CONCLUSIONS: One in 25 patients presenting to hospital for self
      harm will kill themselves in the next 5 years. The incidence of repeat self-harm
      and suicide in this population has not changed in over 10 years. Different
      methods of identifying repeat episodes of self-harm produce varying estimates of
      incidence and this heterogeneity should be considered when evaluating
      interventions aimed at reducing non-fatal repeat self-harm.

PMID- 24587142
TI  - Malignant pleural effusion supernatants are substitutes for metastatic pleural
      tumor tissues in EGFR mutation test in patients with advanced lung
      adenocarcinoma.
AB  - BACKGROUND: Though the possibility of using malignant pleural effusions (MPEs) as
      alternatives for metastatic pleural tumor tissues (MPTTs) in epidermal growth
      factor receptor (EGFR) mutation test has been examined, due to the lack of
      studies comparing the results in matching MPEs and MPTTs, the clinical value of
      MPEs for advanced adenocarcinoma patients with pleural effusions is not
      confirmed. METHODS: EGFR mutation statuses in matching MPTTs, MPE supernatants
      and cell blocks, of 41 patients with advanced lung adenocarcinoma as diagnosed by
      thoracoscopy were analyzed using amplification refractory mutation system (ARMS).
      RESULTS: EGFR mutations were detected in 46.3% (19/41) of MPTTs, 43.9% (18/41) of
      MPE supernatants and 56.3% (18/32) of MPE cell blocks by ARMS analysis.
      Generally, the same EGFR statuses were identified in both MPTTs and matching MPE
      cell blocks of 81.3% patients (26/32), whereas MPTTs and matching MPE
      supernatants of 87.8% (36/41) patients shared the same EGFR status. Compared with
      EGFR mutation detection in MPTTs, the sensitivity of EGFR mutation detection in
      MPE-cell blocks was 87.5% (14/16), specificity was 75.0% (12/16), while the
      sensitivity of EGFR mutation detection in MPE-supernatants was 84.2% (16/19),
      specificity was 90.9% (20/22). CONCLUSIONS: The high concordance of EGFR mutation
      statuses between MPEs and MPTTs in lung adenocarcinoma patients with pleural
      metastasis as determined by ARMS analysis suggests that MPEs, particularly MPE
      supernatants, may be substitutes for MPTTs in EGFR mutation test.

PMID- 24587143
TI  - Introduction of a microsurgical in-vivo embolization-model in rats: the aorta
      filter model.
AB  - Vascular thrombosis with subsequent distal embolization remains a critical event
      for patients. Prevention of this life-threatening event can be achieved
      pharmacologically or mechanically with intravascular filter systems. The ability
      to evaluate the risk of embolization of certain techniques and procedures in
      vascular and microvascular surgery, such as, tissue glue or fibrin based
      haemostatic agents lacks convincing models. We performed 64 microvascular
      anastomoses in 44 rats, including 44 micro-pore polyurethane filter-anastomoses
      and 20 non-filter anastomoses. The rats were re-anesthetized and the aorta was re
      exposed and removed four hours, three, seven, fourteen, thirty-one days, and six
      months postoperatively. The specimens were examined macro- and microscopically
      with regard to the appearance of the vessel wall, condition of the filter and the
      amount of thrombembolic material. Typical postoperative histopathological changes
      in vessel architecture were observed. Media necrosis was the first significant
      change three days postoperatively. Localized intimal hyperplasia, media necrosis,
      increase of media fibromyocytes and adventitial hypercellularity were seen to a
      significant extent at day seven postoperatively. Significant neovascularization
      of adventitia adjacent to the filter was seen after 14 days. A significant amount
      of thrombotic material was seen after four hours, three and 14 days interval.
      Only three intravascular filters became completely occluded (6.82%). The aorta
      filter-anastomosis model appeared to be a valid in-vivo model in situations at
      risk for thrombembolic events, for microsurgical research and allowed sensitive
      analysis of surgical procedures and protection of the vascularized tissue. It may
      be suitable for a wide range of in-vivo microvascular experiments particularly in
      the rat model. 

PMID- 24587144
TI  - Rodent scope: a user-configurable digital wireless telemetry system for freely
      behaving animals.
AB  - This paper describes the design and implementation of a wireless neural telemetry
      system that enables new experimental paradigms, such as neural recordings during
      rodent navigation in large outdoor environments. RoSco, short for Rodent Scope,
      is a small lightweight user-configurable module suitable for digital wireless
      recording from freely behaving small animals. Due to the digital transmission
      technology, RoSco has advantages over most other wireless modules of noise
      immunity and online user-configurable settings. RoSco digitally transmits entire
      neural waveforms for 14 of 16 channels at 20 kHz with 8-bit encoding which are
      streamed to the PC as standard USB audio packets. Up to 31 RoSco wireless modules
      can coexist in the same environment on non-overlapping independent channels. The
      design has spatial diversity reception via two antennas, which makes wireless
      communication resilient to fading and obstacles. In comparison with most existing
      wireless systems, this system has online user-selectable independent gain control
      of each channel in 8 factors from 500 to 32,000 times, two selectable ground
      references from a subset of channels, selectable channel grounding to disable
      noisy electrodes, and selectable bandwidth suitable for action potentials (300 Hz
      3 kHz) and low frequency field potentials (4 Hz-3 kHz). Indoor and outdoor
      recordings taken from freely behaving rodents are shown to be comparable to a
      commercial wired system in sorting for neural populations. The module has low
      input referred noise, battery life of 1.5 hours and transmission losses of 0.1%
      up to a range of 10 m. 

PMID- 24587145
TI  - Poor thermal care practices among home births in Nepal: further analysis of Nepal
      Demographic and Health Survey 2011.
AB  - INTRODUCTION: Hypothermia is a major factor associated with neonatal mortality in
      low and middle income countries. Thermal care protection of newborn through a
      series of measures taken at birth and during the initial days of life is
      recommended to reduce the hypothermia and associated neonatal mortality. This
      study aimed to identify the prevalence of and the factors associated with
      receiving 'optimum thermal care' among home born newborns of Nepal. METHODS: Data
      from the Nepal Demographic and Health Surveys (NDHS) 2011 were used for this
      study. Women who reported a home birth for their most recent childbirth was
      included in the study. Factors associated with optimum thermal care were examined
      using Chi-square test followed by logistic regression. RESULTS: A total of 2464
      newborns were included in the study. A total of 57.6 % were dried before the
      placenta was delivered; 60.3% were wrapped; 24.5% had not bathing during the
      first 24 hours, and 63.9% were breastfed within one hour of birth. Overall, only
      248 (10.7%; 95% CI (8.8 %, 12.9%)) newborns received optimum thermal care.
      Newborns whose mothers had achieved higher education (OR 2.810; 95% CI (1.132,
      6.976)), attended four or more antenatal care visits (OR 2.563; 95% CI (1.309,
      5.017)), and those whose birth were attended by skilled attendants (OR 2.178; 95%
      CI (1.428, 3.323)) were likely to receive optimum thermal care. CONCLUSION: The
      current study showed that only one in ten newborns in Nepal received optimum
      thermal care. Future newborn survival programs should focus on those mothers who
      are uneducated; who do not attend the recommended four or more attend antenatal
      care visits; and those who deliver without the assistance of skilled birth
      attendants to reduce the risk of neonatal hypothermia in Nepal.

PMID- 24587146
TI  - Transcriptomics of the interaction between the monopartite phloem-limited
      geminivirus tomato yellow leaf curl Sardinia virus and Solanum lycopersicum
      highlights a role for plant hormones, autophagy and plant immune system fine
      tuning during infection.
AB  - Tomato yellow leaf curl Sardinia virus (TYLCSV), a DNA virus belonging to the
      genus Begomovirus, causes severe losses in tomato crops. It infects only a
      limited number of cells in the vascular tissues, making difficult to detect
      changes in host gene expression linked to its presence. Here we present the first
      microarray study of transcriptional changes induced by the phloem-limited
      geminivirus TYLCSV infecting tomato, its natural host. The analysis was performed
      on the midrib of mature leaves, a material naturally enriched in vascular
      tissues. A total of 2206 genes were up-regulated and 1398 were down-regulated in
      infected plants, with an overrepresentation of genes involved in hormone
      metabolism and responses, nucleic acid metabolism, regulation of transcription,
      ubiquitin-proteasome pathway and autophagy among those up-regulated, and in
      primary and secondary metabolism, phosphorylation, transcription and methylation
      dependent chromatin silencing among those down-regulated. Our analysis showed a
      series of responses, such as the induction of GA- and ABA-responsive genes, the
      activation of the autophagic process and the fine tuning of the plant immune
      system, observed only in TYLCSV-tomato compatible interaction so far. On the
      other hand, comparisons with transcriptional changes observed in other
      geminivirus-plant interactions highlighted common host responses consisting in
      the deregulation of biotic stress responsive genes, key enzymes in the ethylene
      biosynthesis and methylation cycle, components of the ubiquitin proteasome system
      and DNA polymerases II. The involvement of conserved miRNAs and of solanaceous-
      and tomato-specific miRNAs in geminivirus infection, investigated by integrating
      differential gene expression data with miRNA targeting data, is discussed. 

PMID- 24587147
TI  - Acute neuromuscular adaptation at the spinal level following middle cerebral
      artery occlusion-reperfusion in the rat.
AB  - The purpose of the study was to highlight the acute motor reflex adaptation and
      to deepen functional deficits following a middle cerebral artery occlusion
      reperfusion (MCAO-r). Thirty-six Sprague-Dawley rats were included in this study.
      The middle cerebral artery occlusion (MCAO; 120 min) was performed on 16 rats
      studied at 1 and 7 days, respectively (MCAO-D1 and MCAO-D7, n = 8 for each
      group). The other animals were divided into 3 groups: SHAM-D1 (n = 6), SHAM-D7 (n
      = 6) and Control (n = 8). Rats performed 4 behavioral tests (the elevated body
      swing test, the beam balance test, the ladder-climbing test and the forelimb grip
      force) before the surgery and daily after MCAO-r. H-reflex on triceps brachii was
      measured before and after isometric exercise. Infarction size and cerebral edema
      were respectively assessed by histological (Cresyl violet) and MRI measurements
      at the same time points than H-reflex recordings. Animals with cerebral ischemia
      showed persistent functional deficits during the first week post-MCAO-r. H-reflex
      was not decreased in response to isometric exercise one day after the cerebral
      ischemia contrary to the other groups. The motor reflex regulation was recovered
      7 days post-MCAO-r. This result reflects an acute sensorimotor adaptation at the
      spinal level after MCAO-r.

PMID- 24587148
TI  - A genetic polymorphism of the endogenous opioid dynorphin modulates monetary
      reward anticipation in the corticostriatal loop.
AB  - The dynorphin/kappa-opioid receptor (KOP-R) system has been shown to play a role
      in different types of behavior regulation, including reward-related behavior and
      drug craving. It has been shown that alleles with 3 or 4 repeats (HH genotype) of
      the variable nucleotide tandem repeat (68-bp VNTR) functional polymorphism of the
      prodynorphin (PDYN) gene are associated with higher levels of dynorphin peptides
      than alleles with 1 or 2 repeats (LL genotype). We used fMRI on N = 71
      prescreened healthy participants to investigate the effect of this polymorphism
      on cerebral activation in the limbic-corticostriatal loop during reward
      anticipation. Individuals with the HH genotype showed higher activation than
      those with the LL genotype in the medial orbitofrontal cortex (mOFC) when
      anticipating a possible monetary reward. In addition, the HH genotype showed
      stronger functional coupling (as assessed by effective connectivity analyses) of
      mOFC with VMPFC, subgenual anterior cingulate cortex, and ventral striatum during
      reward anticipation. This hints at a larger sensitivity for upcoming rewards in
      individuals with the HH genotype, resulting in a higher motivation to attain
      these rewards. These findings provide first evidence in humans that the PDYN
      polymorphism modulates neural processes associated with the anticipation of
      rewards, which ultimately may help to explain differences between genotypes with
      respect to addiction and drug abuse.

PMID- 24587149
TI  - Patterns of research effort in birds.
AB  - Between species differences in research effort can lead to biases in our global
      view of evolution, ecology and conservation. The increase in meta-taxonomic
      comparative analyses on birds underlines the need to better address how research
      effort is distributed in this class. Methods have been developed to choose which
      species should be studied to obtain unbiased comparative data sets, but a precise
      and global knowledge of research effort is required to be able to properly apply
      them. We address this issue by providing a data set of research effort (number of
      papers from 1978 to 2008 in the Zoological Record database) estimates for the
      10,064 species of birds. We then test whether research effort is associated with
      phylogeny, geography and eleven different life history and ecological traits. We
      show that phylogeny accounts for a large proportion of the variance, while
      geographic range and all the tested traits are also significant contributors to
      research effort variance. We identify avian taxa that are under- and overstudied
      and address the importance of research effort biases in evaluating vulnerability
      to extinction, with non-threatened species studied twice as much as threatened
      ones. Our research effort data set covering the entire class Aves provides a tool
      for researchers to incorporate this potential confounding variable in comparative
      analyses.

PMID- 24587150
TI  - Genetic determinants of chronic obstructive pulmonary disease in South Indian
      male smokers.
AB  - The development of chronic obstructive pulmonary disease, upon exposure to
      tobacco smoke, is the cumulative effect of defects in several genes. With the aim
      of understanding the genetic structure that is characteristic of our patient
      population, we selected forty two single nucleotide polymorphisms of twenty genes
      based on previous studies and genotyped a total of 382 samples, which included
      236 patients and 146 controls using Sequenom MassARRAY system. Allele frequencies
      of rs2276109 (MMP12) and rs1800925 (IL13) differed significantly between patients
      and controls (p = 0.013 and 0.044 respectively). Genotype analysis showed
      association of rs2276109 (MMP12) under additive and dominant models (p = 0.017, p
      = 0.012 respectively), rs1800925 (IL13) under additive model (p = 0.047) and
      under recessive model, rs1695 (GSTP1; p = 0.034), rs729631, rs975278, rs7583463
      (SERPINE2; p = 0.024, 0.024 and 0.012 respectively), rs2568494, rs10851906
      (IREB2; p = 0.026 and 0.041 respectively) and rs7671167 (FAM13A; p = 0.029). The
      minor alleles of rs1695 (G), rs7671167 (T), rs729631 (G), rs975278 (A) and
      rs7583463 (A) showed significant negative association whereas those of rs2276109
      (G), rs2568494 (A), rs10851906 (G) and rs1800469 (T; TGF-beta) showed significant
      positive association with lung function under different genetic models.
      Haplotypes carrying A allele of rs2276109, G allele of rs1695 showed negative
      correlation with lung function. Haplotypes carrying major alleles of rs7671167
      (C) of FAM13A and rs729631 (C), rs975278 (G), rs7583463 (C) of SERPINE2 had
      protective effect on lung function. Haplotypes of IREB2 carrying major alleles of
      rs2568494 (G), rs2656069 (A), rs10851906 (A), rs965604 (C) and minor alleles of
      rs1964678 (T), rs12593229 (T) showed negative correlation with lung function. In
      conclusion, our study replicated the results of most of the previous studies.
      However, the positive correlation between the minor alleles of rs2568494 (A) and
      rs10851906 (G) of IREB2 and lung function needs further investigation. 

PMID- 24587151
TI  - Transcriptomic analysis of (group I) Clostridium botulinum ATCC 3502 cold shock
      response.
AB  - Profound understanding of the mechanisms foodborne pathogenic bacteria utilize in
      adaptation to the environmental stress they encounter during food processing and
      storage is of paramount importance in design of control measures. Chill
      temperature is a central control measure applied in minimally processed foods;
      however, data on the mechanisms the foodborne pathogen Clostridium botulinum
      activates upon cold stress are scarce. Transcriptomic analysis on the C.
      botulinum ATCC 3502 strain upon temperature downshift from 37 degrees C to 15
      degrees C was performed to identify the cold-responsive gene set of this
      organism. Significant up- or down-regulation of 16 and 11 genes, respectively,
      was observed 1 h after the cold shock. At 5 h after the temperature downshift,
      199 and 210 genes were up- or down-regulated, respectively. Thus, the relatively
      small gene set affected initially indicated a targeted acute response to cold
      shock, whereas extensive metabolic remodeling appeared to take place after
      prolonged exposure to cold. Genes related to fatty acid biosynthesis, oxidative
      stress response, and iron uptake and storage were induced, in addition to
      mechanisms previously characterized as cold-tolerance related in bacteria.
      Furthermore, several uncharacterized DNA-binding transcriptional regulator
      encoding genes were induced, suggesting involvement of novel regulatory
      mechanisms in the cold shock response of C. botulinum. The role of such
      regulators, CBO0477 and CBO0558A, in cold tolerance of C. botulinum ATCC 3502 was
      demonstrated by deteriorated growth of related mutants at 17 degrees C. 

PMID- 24587152
TI  - Disparities and risks of sexually transmissible infections among men who have sex
      with men in China: a meta-analysis and data synthesis.
AB  - BACKGROUND: Sexually transmitted infections (STIs), including Hepatitis B and C
      virus, are emerging public health risks in China, especially among men who have
      sex with men (MSM). This study aims to assess the magnitude and risks of STIs
      among Chinese MSM. METHODS: Chinese and English peer-reviewed articles were
      searched in five electronic databases from January 2000 to February 2013. Pooled
      prevalence estimates for each STI infection were calculated using meta-analysis.
      Infection risks of STIs in MSM, HIV-positive MSM and male sex workers (MSW) were
      obtained. This review followed the PRISMA guidelines and was registered in
      PROSPERO. RESULTS: Eighty-eight articles (11 in English and 77 in Chinese)
      investigating 35,203 MSM in 28 provinces were included in this review. The
      prevalence levels of STIs among MSM were 6.3% (95% CI: 3.5-11.0%) for chlamydia,
      1.5% (0.7-2.9%) for genital wart, 1.9% (1.3-2.7%) for gonorrhoea, 8.9% (7.8
      10.2%) for hepatitis B (HBV), 1.2% (1.0-1.6%) for hepatitis C (HCV), 66.3% (57.4
      74.1%) for human papillomavirus (HPV), 10.6% (6.2-17.6%) for herpes simplex virus
      (HSV-2) and 4.3% (3.2-5.8%) for Ureaplasma urealyticum. HIV-positive MSM have
      consistently higher odds of all these infections than the broader MSM population.
      As a subgroup of MSM, MSW were 2.5 (1.4-4.7), 5.7 (2.7-12.3), and 2.2 (1.4-3.7)
      times more likely to be infected with chlamydia, gonorrhoea and HCV than the
      broader MSM population, respectively. CONCLUSION: Prevalence levels of STIs among
      MSW were significantly higher than the broader MSM population. Co-infection of
      HIV and STIs were prevalent among Chinese MSM. Integration of HIV and STIs
      healthcare and surveillance systems is essential in providing effective HIV/STIs
      preventive measures and treatments. TRIAL REGISTRATION: PROSPERO NO:
      CRD42013003721.

PMID- 24587153
TI  - Luteoloside suppresses proliferation and metastasis of hepatocellular carcinoma
      cells by inhibition of NLRP3 inflammasome.
AB  - The inflammasome is a multi-protein complex which when activated regulates
      caspase-1 activation and IL-1beta secretion. Inflammasome activation is mediated
      by NLR proteins that respond to stimuli. Among NLRs, NLRP3 senses the widest
      array of stimuli. NLRP3 inflammasome plays an important role in the development
      of many cancer types. However, Whether NLRP3 inflammasome plays an important role
      in the process of hepatocellular carcinoma (HCC) is still unknown. Here, the
      anticancer effect of luteoloside, a naturally occurring flavonoid isolated from
      the medicinal plant Gentiana macrophylla, against HCC cells and the underlying
      mechanisms were investigated. Luteoloside significantly inhibited the
      proliferation of HCC cells in vitro and in vivo. Live-cell imaging and transwell
      assays showed that the migration and invasive capacities of HCC cells, which were
      treated with luteoloside, were significantly inhibited compared with the control
      cells. The inhibitory effect of luteoloside on metastasis was also observed in
      vivo in male BALB/c-nu/nu mouse lung metastasis model. Further studies showed
      that luteoloside could significantly reduce the intracellular reactive oxygen
      species (ROS) accumulation. The decreased levels of ROS induced by luteoloside
      was accompanied by decrease in expression of NLRP3 inflammasome resulting in
      decrease in proteolytic cleavage of caspase-1. Inactivation of caspase-1 by
      luteoloside resulted in inhibition of IL-1beta. Thus, luteoloside exerts its
      inhibitory effect on proliferation, invasion and metastasis of HCC cells through
      inhibition of NLRP3 inflammasome. Our results indicate that luteoloside can be a
      potential therapeutic agent not only as an adjuvant therapy for HCC, but also, in
      the control and prevention of metastatic HCC. 

PMID- 24587154
TI  - Proteomic analysis of differentially expressed proteins in Fenneropenaeus
      chinensis hemocytes upon white spot syndrome virus infection.
AB  - To elucidate molecular responses of shrimp hemocytes to white spot syndrome virus
      (WSSV) infection, two-dimensional gel electrophoresis was applied to investigate
      differentially expressed proteins in hemocytes of Chinese shrimp (Fenneropenaeus
      chinensis) at 24 h post infection (hpi). Approximately 580 protein spots were
      detected in hemocytes of healthy and WSSV-infected shrimps. Quantitative
      intensity analysis revealed 26 protein spots were significantly up-regulated, and
      19 spots were significantly down-regulated. By mass spectrometry, small ubiquitin
      like modifier (SUMO) 1, cytosolic MnSOD, triosephosphate isomerase, tubulin alpha
      1 chain, microtubule-actin cross-linking factor 1, nuclear receptor E75 protein,
      vacuolar ATP synthase subunit B L form, inositol 1,4,5-trisphosphate receptor,
      arginine kinase, etc., amounting to 33 differentially modulated proteins were
      identified successfully. According to Gene Ontology annotation, the identified
      proteins were classified into nine categories, consisting of immune related
      proteins, stimulus response proteins, proteins involved in glucose metabolic
      process, cytoskeleton proteins, DNA or protein binding proteins, proteins
      involved in steroid hormone mediated signal pathway, ATP synthases, proteins
      involved in transmembrane transport and ungrouped proteins. Meanwhile, the
      expression profiles of three up-regulated proteins (SUMO, heat shock protein 70,
      and arginine kinase) and one down-regulated protein (prophenoloxidase) were
      further analyzed by real-time RT-PCR at the transcription level after WSSV
      infection. The results showed that SUMO and heat shock protein 70 were
      significantly up-regulated at each sampling time point, while arginine kinase was
      significantly up-regulated at 12 and 24 hpi. In contrast, prophenoloxidase was
      significantly down-regulated at each sampling time point. The results of this
      work provided preliminary data on proteins in shrimp hemocytes involved in WSSV
      infection. 

PMID- 24587155
TI  - Genome sequencing of Listeria monocytogenes "Quargel" listeriosis outbreak
      strains reveals two different strains with distinct in vitro virulence potential.
AB  - A large listeriosis outbreak occurred in Austria, Germany and the Czech Republic
      in 2009 and 2010. The outbreak was traced back to a traditional Austrian curd
      cheese called "Quargel" which was contaminated with two distinct serovar 1/2a
      Listeria monocytogenes strains (QOC1 and QOC2). In this study we sequenced and
      analysed the genomes of both outbreak strains in order to investigate the extent
      of genetic diversity between the two strains belonging to MLST sequence types 398
      (QOC2) and 403 (QOC1). Both genomes are highly similar, but also display distinct
      properties: The QOC1 genome is approximately 74 kbp larger than the QOC2 genome.
      In addition, the strains harbour 93 (QOC1) and 45 (QOC2) genes encoding strain
      specific proteins. A 21 kbp region showing highest similarity to plasmid pLMIV
      encoding three putative internalins is integrated in the QOC1 genome. In contrast
      to QOC1, strain QOC2 harbours a vip homologue, which encodes a LPXTG surface
      protein involved in cell invasion. In accordance, in vitro virulence assays
      revealed distinct differences in invasion efficiency and intracellular
      proliferation within different cell types. The higher virulence potential of QOC1
      in non-phagocytic cells may be explained by the presence of additional
      internalins in the pLMIV-like region, whereas the higher invasion capability of
      QOC2 into phagocytic cells may be due to the presence of a vip homologue. In
      addition, both strains show differences in stress-related gene content. Strain
      QOC1 encodes a so-called stress survival islet 1, whereas strain QOC2 harbours a
      homologue of the uncharacterized LMOf2365_0481 gene. Consistently, QOC1 shows
      higher resistance to acidic, alkaline and gastric stress. In conclusion, our
      results show that strain QOC1 and QOC2 are distinct and did not recently evolve
      from a common ancestor. 

PMID- 24587156
TI  - A microfluidic-based multi-shear device for investigating the effects of low
      fluid-induced stresses on osteoblasts.
AB  - Interstitial fluid flow (IFF) within the extracellular matrix (ECM) produces low
      magnitude shear stresses on cells. Fluid flow-induced stress (FSS) plays an
      important role during tissue morphogenesis. To investigate the effect of low FSS
      generated by IFF on cells, we developed a microfluidic-based cell culture device
      that can generate multiple low shear stresses. By changing the length and width
      of the flow-in channels, different continuous low level shear stresses could be
      generated in individual cell culture chambers. Numerical calculations demonstrate
      uniform shear stress distributions of the major cell culture area of each
      chamber. This calculation is further confirmed by the wall shear stress curves.
      The effects of low FSS on MC3T3-E1 proliferation and differentiation were studied
      using this device. It was found that FSS ranging from 1.5 to 52.6 uPa promoted
      MC3T3-E1 proliferation and differentiation, but FSS over 412 uPa inhibited the
      proliferation and differentiation of MC3T3-E1 cells. FSS ranging from 1.5 to 52.6
      uPa also increased the expression of Runx2, a key transcription factor regulating
      osteoblast differentiation. It is suggested that Runx2 might be an important
      regulator in low FSS-induced MC3T3-E1 differentiation. This device allows for
      detailed study of the effect of low FSS on the behaviors of cells; thus, it would
      be a useful tool for analysis of the effects of IFF-induced shear stresses on
      cells. 

PMID- 24587157
TI  - Polymeric micelles for apoptosis-targeted optical imaging of cancer and
      intraoperative surgical guidance.
AB  - In a two-step strategy, an intraperitoneal (IP) injection of poly(ethylene
      glycol)-block-poly(epsilon-caprolactone) (PEG-b-PCL) micelles containing
      paclitaxel (PTX), cyclopamine (CYP), and gossypol (GSP) at 30, 30, and 30 mg/kg,
      respectively, debulked tumor tissues by 1.3-fold, based on loss of
      bioluminescence with <10% body weight change, and induced apoptosis in peritoneal
      tumors when used as neoadjuvant chemotherapy (NACT) in an ES-2-luc-bearing
      xenograft model for ovarian cancer. In a second step, a single intravenous (i.v.)
      injection of apoptosis-targeting GFNFRLKAGAKIRFGS-PEG-b-PCL micelles containing a
      near-infrared (NIR) fluorescence probe, DiR (1,1'-dioctadecyltetramethyl
      indotricarbocyanine iodide), resulted in increased peritoneal DiR accumulation in
      apoptosis-induced ES-2-luc tumor tissues (ex vivo) by 1.5-fold compared with DiR
      molecules delivered by methoxy PEG-b-PCL micelles (non-targeted) at 48 h after
      i.v. injection in a second step. As a result, a tandem of PEG-b-PCL micelles
      enabled high-resolution detection of ca. 1 mm diameter tumors, resulting in
      resection of approximately 90% of tumors, and a low peritoneal cancer index (PCI)
      of ca. 7. Thus, a tandem of PEG-b-PCL micelles used for NCAT and NIR fluorescence
      imaging of therapy-induced apoptosis for intraoperative surgical guidance may be
      a promising treatment strategy for metastatic ovarian cancer.

PMID- 24587160
TI  - Encouraging family forest owners to create early successional wildlife habitat in
      Southern New England.
AB  - Encouraging family forest owners to create early successional habitat is a high
      priority for wildlife conservation agencies in the northeastern USA, where most
      forest land is privately owned. Many studies have linked regional declines in
      wildlife populations to the loss of early successional habitat. The government
      provides financial incentives to create early successional habitat, but the
      number of family forest owners who actively manage their forests remains low.
      Several studies have analyzed participation of family forest owners in federal
      forestry programs, but no study to date has focused specifically on creation of
      wildlife habitat. The objective of our study was to analyze the experience of a
      group of wildlife-oriented family forest owners who were trained to create early
      successional habitat. This type of family forest owners represents a small
      portion of the total population of family forest owners, but we believe they can
      play an important role in creating wildlife habitat, so it is important to
      understand how outreach programs can best reach them. The respondents shared some
      characteristics but differed in terms of forest holdings, forestry experience and
      interest in earning forestry income. Despite their strong interest in wildlife,
      awareness about the importance of early successional habitat was low. Financial
      support from the federal government appeared to be important in motivating
      respondents to follow up after the training with activities on their own
      properties: 84% of respondents who had implemented activities received federal
      financial support and 47% would not have implemented the activities without
      financial assistance. In order to mobilize greater numbers of wildlife-oriented
      family forest owners to create early successional habitat we recommend focusing
      outreach efforts on increasing awareness about the importance of early
      successional habitat and the availability of technical and financial assistance. 

PMID- 24587158
TI  - Impact of age on the cerebrovascular proteomes of wild-type and Tg-SwDI mice.
AB  - The structural integrity of cerebral vessels is compromised during ageing.
      Abnormal amyloid (Abeta) deposition in the vasculature can accelerate age-related
      pathologies. The cerebrovascular response associated with ageing and
      microvascular Abeta deposition was defined using quantitative label-free shotgun
      proteomic analysis. Over 650 proteins were quantified in vessel-enriched
      fractions from the brains of 3 and 9 month-old wild-type (WT) and Tg-SwDI mice.
      Sixty-five proteins were significantly increased in older WT animals and included
      several basement membrane proteins (nidogen-1, basement membrane-specific heparan
      sulfate proteoglycan core protein, laminin subunit gamma-1 precursor and collagen
      alpha-2(IV) chain preproprotein). Twenty-four proteins were increased and twenty
      one decreased in older Tg-SwDI mice. Of these, increases in Apolipoprotein E
      (APOE) and high temperature requirement serine protease-1 (HTRA1) and decreases
      in spliceosome and RNA-binding proteins were the most prominent. Only six shared
      proteins were altered in both 9-month old WT and Tg-SwDI animals. The age-related
      proteomic response in the cerebrovasculature was distinctly different in the
      presence of microvascular Abeta deposition. Proteins found differentially
      expressed within the WT and Tg-SwDI animals give greater insight to the
      mechanisms behind age-related cerebrovascular dysfunction and pathologies and may
      provide novel therapeutic targets. 

PMID- 24587159
TI  - Transient replication of Hepatitis C Virus sub-genomic RNA in murine cell lines
      is enabled by miR-122 and varies with cell passage.
AB  - Hepatitis C Virus (HCV) is a serious global health problem, infecting almost 3%
      of the world's population. The lack of model systems for studying this virus
      limit research options in vaccine and therapeutic development, as well as for
      studying the pathogenesis of chronic HCV infection. Herein we make use of the
      liver-specific microRNA miR-122 to render mouse cell lines permissive to HCV
      replication in an attempt to develop additional model systems for the
      identification of new features of the virus and its life cycle. We have
      determined that some wild-type and knockout mouse cell lines--NCoA6 and PKR
      knockout embryonic fibroblasts--can be rendered permissive to transient HCV sub
      genomic RNA replication upon addition of miR-122, but we did not observe
      replication of full-length HCV RNA in these cells. However, other wild-type and
      knockout cell lines cannot be rendered permissive to HCV replication by addition
      of miR-122, and in fact, different NCoA6 and PKR knockout cell line passages and
      isolates from the same mice demonstrated varying permissiveness phenotypes and
      eventually complete loss of permissiveness. When we tested knockdown of NCoA6 and
      PKR in Huh7.5 cells, we saw no substantial impact in sub-genomic HCV replication,
      which we would expect if these genes were inhibitory to the virus' life cycle.
      This leads us to conclude that along with the influence of specific gene
      knockouts there are additional factors within the cell lines that affect their
      permissiveness for HCV replication; we suggest that these may be epigenetically
      regulated, or modulated by cell line immortalization and transformation.

PMID- 24587161
TI  - DNA damage induces down-regulation of Prp19 via impairing Prp19 stability in
      hepatocellular carcinoma cells.
AB  - Pre-mRNA processing factor 19 (Prp19) activates pre-mRNA spliceosome and also
      mediates DNA damage response. Prp19 overexpression in cells with functional p53
      leads to decreased apoptosis and increases cell survival after DNA damage. Here
      we showed that in hepatocellular carcinoma (HCC) cells with inactive p53 or
      functional p53, Prp19 was down-regulated due to the impaired stability under
      chemotherapeutic drug treatment. Silencing Prp19 expression enhanced apoptosis of
      HCC cells with or without chemotherapeutic drug treatment. Furthermore high level
      of Prp19 may inhibit chemotherapeutic drugs induced apoptosis in hepatocellular
      carcinoma cells through modulating myeloid leukemia cell differentiation 1
      expression. These results indicated that targeting Prp19 may potentiate pro
      apoptotic effect of chemotherapeutic agents on HCC. 

PMID- 24587162
TI  - The role of SGLT1 and GLUT2 in intestinal glucose transport and sensing.
AB  - Intestinal glucose absorption is mediated by SGLT1 whereas GLUT2 is considered to
      provide basolateral exit. Recently, it was proposed that GLUT2 can be recruited
      into the apical membrane after a high luminal glucose bolus allowing bulk
      absorption of glucose by facilitated diffusion. Moreover, SGLT1 and GLUT2 are
      suggested to play an important role in intestinal glucose sensing and incretin
      secretion. In mice that lack either SGLT1 or GLUT2 we re-assessed the role of
      these transporters in intestinal glucose uptake after radiotracer glucose gavage
      and performed Western blot analysis for transporter abundance in apical membrane
      fractions in a comparative approach. Moreover, we examined the contribution of
      these transporters to glucose-induced changes in plasma GIP, GLP-1 and insulin
      levels. In mice lacking SGLT1, tissue retention of tracer glucose was drastically
      reduced throughout the entire small intestine whereas GLUT2-deficient animals
      exhibited higher tracer contents in tissue samples than wild type animals.
      Deletion of SGLT1 resulted also in reduced blood glucose elevations and abolished
      GIP and GLP-1 secretion in response to glucose. In mice lacking GLUT2, glucose
      induced insulin but not incretin secretion was impaired. Western blot analysis
      revealed unchanged protein levels of SGLT1 after glucose gavage. GLUT2 detected
      in apical membrane fractions mainly resulted from contamination with basolateral
      membranes but did not change in density after glucose administration. SGLT1 is
      unequivocally the prime intestinal glucose transporter even at high luminal
      glucose concentrations. Moreover, SGLT1 mediates glucose-induced incretin
      secretion. Our studies do not provide evidence for GLUT2 playing any role in
      either apical glucose influx or incretin secretion. 

PMID- 24587163
TI  - Population-based incidence of severe acute respiratory virus infections among
      children aged <5 years in rural Bangladesh, June-October 2010.
AB  - BACKGROUND: Better understanding the etiology-specific incidence of severe acute
      respiratory infections (SARIs) in resource-poor, rural settings will help further
      develop and prioritize prevention strategies. To address this gap in knowledge,
      we conducted a longitudinal study to estimate the incidence of SARIs among
      children in rural Bangladesh. METHODS: During June through October 2010, we
      followed children aged <5 years in 67 villages to identify those with cough,
      difficulty breathing, age-specific tachypnea and/or danger signs in the community
      or admitted to the local hospital. A study physician collected clinical
      information and obtained nasopharyngeal swabs from all SARI cases and blood for
      bacterial culture from those hospitalized. We tested swabs for respiratory
      syncytial virus (RSV), influenza viruses, human metapneumoviruses, adenoviruses
      and human parainfluenza viruses 1-3 (HPIV) by real-time reverse transcription
      polymerase chain reaction. We calculated virus-specific SARI incidence by
      dividing the number of new illnesses by the person-time each child contributed to
      the study. RESULTS: We followed 12,850 children for 279,029 person-weeks (pw) and
      identified 141 SARI cases; 76 (54%) at their homes and 65 (46%) at the hospital.
      RSV was associated with 7.9 SARI hospitalizations per 100,000 pw, HPIV3 2.2
      hospitalizations/100,000 pw, and influenza 1.1 hospitalizations/100,000 pw. Among
      non-hospitalized SARI cases, RSV was associated with 10.8 illnesses/100,000 pw,
      HPIV3 1.8/100,000 pw, influenza 1.4/100,000 pw, and adenoviruses 0.4/100,000 pw.
      CONCLUSION: Respiratory viruses, particularly RSV, were commonly associated with
      SARI among children. It may be useful to explore the value of investing in
      prevention strategies, such as handwashing and respiratory hygiene, to reduce
      respiratory infections among young children in such settings.

PMID- 24587164
TI  - Epigenetic upregulation of endogenous VEGF-A reduces myocardial infarct size in
      mice.
AB  - "Epigenetherapy" alters epigenetic status of the targeted chromatin and modifies
      expression of the endogenous therapeutic gene. In this study we used lentiviral
      in vivo delivery of small hairpin RNA (shRNA) into hearts in a murine infarction
      model. shRNA complementary to the promoter of vascular endothelial growth factor
      (VEGF-A) was able to upregulate endogenous VEGF-A expression. Histological and
      multiphoton microscope analysis confirmed the therapeutic effect in the
      transduced hearts. Magnetic resonance imaging (MRI) showed in vivo that the
      infarct size was significantly reduced in the treatment group 14 days after the
      epigenetherapy. Importantly, we show that promoter-targeted shRNA upregulates all
      isoforms of endogenous VEGF-A and that an intact hairpin structure is required
      for the shRNA activity. In conclusion, regulation of gene expression at the
      promoter level is a promising new treatment strategy for myocardial infarction
      and also potentially useful for the upregulation of other endogenous genes. 

PMID- 24587165
TI  - Deciphering the stromal and hematopoietic cell network of the adventitia from non
      aneurysmal and aneurysmal human aorta.
AB  - Aneurysm is associated to a complex remodeling of arteries that affects all their
      layers. Although events taking place in the intima and the media have received a
      particular attention, molecular and cellular events taking place in the
      adventitia have started to be deciphered only recently. In this study, we have
      precisely described the composition and distribution of stromal and hematopoietic
      cells in human arterial adventitia, both at steady state and in the setting of
      aortic aneurysm. Using polychromatic immunofluorescent and flow cytometry
      analyses, we observed that unlike the medial layer (which comprises mostly
      macrophages and T cells among leukocytes), the adventitia comprises a much
      greater variety of leukocytes. We observed an altered balance in macrophages
      subsets in favor of M2-like macrophages, an increased proliferation of
      macrophages, a greater number of all stromal cells in aneurysmal aortas. We also
      confirmed that in this pathological setting, adventitia comprised blood vessels
      and arterial tertiary lymphoid organs (ATLOs), which contained also M-DC8(+)
      dendritic cells (slanDCs) that could participate in the induction of T-cell
      responses. Finally, we showed that lymphatic vessels can be detected in
      aneurysmal adventitia, the functionality of which will have to be evaluated in
      future studies. All together, these observations provide an integrative outlook
      of the stromal and hematopoietic cell network of the human adventitia both at
      steady state and in the context of aneurysm. 

PMID- 24587166
TI  - The impact of antimicrobial resistance and aging in VAP outcomes: experience from
      a large tertiary care center.
AB  - BACKGROUND: Ventilator associated pneumonia (VAP) is a serious infection among
      patients in the intensive care unit (ICU). METHODS: We reviewed the medical
      charts of all patients admitted to the adult intensive care units of the
      Massachusetts General Hospital that went on to develop VAP during a five year
      period. RESULTS: 200 patients were included in the study of which 50 (25%) were
      infected with a multidrug resistant pathogen. Increased age, dialysis and late
      onset (>= 5 days from admission) VAP were associated with increased incidence of
      resistance. Multidrug resistant bacteria (MDRB) isolation was associated with a
      significant increase in median length of ICU stay (19 vs. 16 days, p=0.02) and
      prolonged duration of mechanical ventilation (18 vs. 14 days, p=0.03), but did
      not impact overall mortality (HR 1.12, 95% CI 0.51-2.46, p=0.77). However, age
      (HR 1.04 95% CI 1.01-1.07, p=0.003) was an independent risk factor for mortality
      and age >= 65 years was associated with increased incidence of methicillin
      resistant Staphylococcus aureus (MRSA) infections (OR 2.83, 95% CI 1.27-6.32,
      p=0.01). CONCLUSIONS: MDRB-related VAP is associated with prolonged ICU stay and
      mechanical ventilation. Interestingly, age >= 65 years is associated with MRSA
      VAP.

PMID- 24587167
TI  - Involvement of sigma-1 receptors in the antidepressant-like effects of
      dextromethorphan.
AB  - Dextromethorphan is an antitussive with a high margin of safety that has been
      hypothesized to display rapid-acting antidepressant activity based on
      pharmacodynamic similarities to the N-methyl-D-aspartate (NMDA) receptor
      antagonist ketamine. In addition to binding to NMDA receptors, dextromethorphan
      binds to sigma-1 (sigma1) receptors, which are believed to be protein targets for
      a potential new class of antidepressant medications. The purpose of this study
      was to determine whether dextromethorphan elicits antidepressant-like effects and
      the involvement of sigma1 receptors in mediating its antidepressant-like actions.
      The antidepressant-like effects of dextromethorphan were assessed in male, Swiss
      Webster mice using the forced swim test. Next, sigma1 receptor antagonists
      (BD1063 and BD1047) were evaluated in conjunction with dextromethorphan to
      determine the involvement of sigma receptors in its antidepressant-like effects.
      Quinidine, a cytochrome P450 (CYP) 2D6 inhibitor, was also evaluated in
      conjunction with dextromethorphan to increase the bioavailability of
      dextromethorphan and reduce exposure to additional metabolites. Finally,
      saturation binding assays were performed to assess the manner in which
      dextromethorphan interacts at the sigma1 receptor. Our results revealed
      dextromethorphan displays antidepressant-like effects in the forced swim test
      that can be attenuated by pretreatment with sigma1 receptor antagonists, with
      BD1063 causing a shift to the right in the dextromethorphan dose response curve.
      Concomitant administration of quinidine potentiated the antidepressant-like
      effects of dextromethorphan. Saturation binding assays revealed that a Ki
      concentration of dextromethorphan reduces both the Kd and the Bmax of [(3)H](+)
      pentazocine binding to sigma1 receptors. Taken together, these data suggest that
      dextromethorphan exerts some of its antidepressant actions through sigma1
      receptors. 

PMID- 24587168
TI  - Computational prediction of neutralization epitopes targeted by human anti-V3 HIV
      monoclonal antibodies.
AB  - The extreme diversity of HIV-1 strains presents a formidable challenge for HIV-1
      vaccine design. Although antibodies (Abs) can neutralize HIV-1 and potentially
      protect against infection, antibodies that target the immunogenic viral surface
      protein gp120 have widely variable and poorly predictable cross-strain
      reactivity. Here, we developed a novel computational approach, the Method of
      Dynamic Epitopes, for identification of neutralization epitopes targeted by anti
      HIV-1 monoclonal antibodies (mAbs). Our data demonstrate that this approach,
      based purely on calculated energetics and 3D structural information, accurately
      predicts the presence of neutralization epitopes targeted by V3-specific mAbs
      2219 and 447-52D in any HIV-1 strain. The method was used to calculate the range
      of conservation of these specific epitopes across all circulating HIV-1 viruses.
      Accurately identifying an Ab-targeted neutralization epitope in a virus by
      computational means enables easy prediction of the breadth of reactivity of
      specific mAbs across the diversity of thousands of different circulating HIV-1
      variants and facilitates rational design and selection of immunogens mimicking
      specific mAb-targeted epitopes in a multivalent HIV-1 vaccine. The defined
      epitopes can also be used for the purpose of epitope-specific analyses of
      breakthrough sequences recorded in vaccine clinical trials. Thus, our study is a
      prototype for a valuable tool for rational HIV-1 vaccine design. 

PMID- 24587169
TI  - Implicit self-esteem decreases in adolescence: a cross-sectional study.
AB  - Implicit self-esteem has remained an active research topic in both the areas of
      implicit social cognition and self-esteem in recent decades. The purpose of this
      study is to explore the development of implicit self-esteem in adolescents. A
      total of 599 adolescents from junior and senior high schools in East China
      participated in the study. They ranged in age from 11 to 18 years with a mean age
      of 14.10 (SD = 2.16). The degree of implicit self-esteem was assessed using the
      Implicit Association Test (IAT) with the improved D score as the index.
      Participants also completed the Rosenberg Self-Esteem Scale (alpha = 0.77). For
      all surveyed ages, implicit self-esteem was positively biased, all ts>8.59, all
      ps<0.001. The simple correlation between implicit self-esteem and age was
      significant, r =  -.25, p = 1. 10(-10). A regression with implicit self-esteem as
      the criterion variable, and age, gender, and age * gender interaction as
      predictors further revealed the significant negative linear relationship between
      age and implicit self-esteem, beta = -0.19, t = -3.20, p = 0.001. However,
      explicit self-esteem manifested a reverse "U" shape throughout adolescence.
      Implicit self-esteem in adolescence manifests a declining trend with increasing
      age, suggesting that it is sensitive to developmental or age-related changes.
      This finding enriches our understanding of the development of implicit social
      cognition.

PMID- 24587170
TI  - Effects of visual working memory on brain information processing of irrelevant
      auditory stimuli.
AB  - Selective attention has traditionally been viewed as a sensory processing
      modulator that promotes cognitive processing efficiency by favoring relevant
      stimuli while inhibiting irrelevant stimuli. However, the cross-modal processing
      of irrelevant information during working memory (WM) has been rarely
      investigated. In this study, the modulation of irrelevant auditory information by
      the brain during a visual WM task was investigated. The N100 auditory evoked
      potential (N100-AEP) following an auditory click was used to evaluate the
      selective attention to auditory stimulus during WM processing and at rest. N100
      AEP amplitudes were found to be significantly affected in the left-prefrontal,
      mid-prefrontal, right-prefrontal, left-frontal, and mid-frontal regions while
      performing a high WM load task. In contrast, no significant differences were
      found between N100-AEP amplitudes in WM states and rest states under a low WM
      load task in all recorded brain regions. Furthermore, no differences were found
      between the time latencies of N100-AEP troughs in WM states and rest states while
      performing either the high or low WM load task. These findings suggested that the
      prefrontal cortex (PFC) may integrate information from different sensory channels
      to protect perceptual integrity during cognitive processing. 

PMID- 24587171
TI  - Neutrophils infiltration in the tongue squamous cell carcinoma and its
      correlation with CEACAM1 expression on tumor cells.
AB  - OBJECTIVE: The present study aimed to explore the clinical significance of
      neutrophils infiltration and carcinoembryonic antigen related cell adhesion
      molecule 1 (CEACAM1) expression in the tongue squamous cell carcinoma (TSCC), and
      to probe the possible relationship between them. MATERIALS AND METHODS: Tissue
      microarray and immunohistochemistry were used to detect neutrophils density and
      CEACAM1 expression in 74 cases of primary TSCC specimens and 17 cases of
      corresponding peritumoral tissues. The relationship of CEACAM1 expression and
      neutrophils density with clinicopathologic parameters and cancer-related survival
      of TSCC patients were evaluated. The correlation between CEACAM1 expression and
      neutrophils density was also evaluated. Real-time quantitative transcription
      polymerase chain reaction (qRT-PCR) was used to explore the possible molecular
      mechanisms between CEACAM1 expression and neutrophils infiltration. RESULTS:
      Immunohistochemistry evaluation revealed that there was more neutrophils
      infiltration in TSCC tissues than in peritumoral tissues. High neutrophil density
      was associated with LN metastasis (P=0.01), higher clinical stage (P=0.037) and
      tumor recurrence (P=0.024). CEACAM1 overexpression was also associated with lymph
      node metastasis (P=0.000) and higher clinical stage (P=0.001). Survival analysis
      revealed that both neutrophils infiltration and CEACAM1 overexpression were
      associated with poorer cancer-related survival of TSCC patients (P<0.05), and
      neutrophils infiltration was an independent prognostic factor for TSCC (P<0.05).
      Furthermore, overexpression of CEACAM1 was correlated with more neutrophils
      infiltration in TSCC tissues (P<0.01). qRT-PCR results showed that CEACAM1-4L can
      upregulate the mRNA expression of IL-8 and CXCL-6, which were strong chemotactic
      factors of neutrophils. CONCLUSION: Our results demonstrated that more
      neutrophils infiltration and overexpression of CEACAM1 were associated with poor
      clinical outcomes in TSCC tissues. Overexpression of CEACAM1 on tumor cells
      correlated with more neutrophils infiltration to some extent through upregulating
      mRNA expression of IL-8 and CXCL-6.

PMID- 24587172
TI  - Selectivity and sparseness in randomly connected balanced networks.
AB  - Neurons in sensory cortex show stimulus selectivity and sparse population
      response, even in cases where no strong functionally specific structure in
      connectivity can be detected. This raises the question whether selectivity and
      sparseness can be generated and maintained in randomly connected networks. We
      consider a recurrent network of excitatory and inhibitory spiking neurons with
      random connectivity, driven by random projections from an input layer of stimulus
      selective neurons. In this architecture, the stimulus-to-stimulus and neuron-to
      neuron modulation of total synaptic input is weak compared to the mean input.
      Surprisingly, we show that in the balanced state the network can still support
      high stimulus selectivity and sparse population response. In the balanced state,
      strong synapses amplify the variation in synaptic input and recurrent inhibition
      cancels the mean. Functional specificity in connectivity emerges due to the
      inhomogeneity caused by the generative statistical rule used to build the
      network. We further elucidate the mechanism behind and evaluate the effects of
      model parameters on population sparseness and stimulus selectivity. Network
      response to mixtures of stimuli is investigated. It is shown that a balanced
      state with unselective inhibition can be achieved with densely connected input to
      inhibitory population. Balanced networks exhibit the "paradoxical" effect: an
      increase in excitatory drive to inhibition leads to decreased inhibitory
      population firing rate. We compare and contrast selectivity and sparseness
      generated by the balanced network to randomly connected unbalanced networks.
      Finally, we discuss our results in light of experiments. 

PMID- 24587173
TI  - A systems biological approach reveals multiple crosstalk mechanism between gram
      positive and negative bacterial infections: an insight into core mechanism and
      unique molecular signatures.
AB  - BACKGROUND: Bacterial infections remain a major threat and a leading cause of
      death worldwide. Most of the bacterial infections are caused by gram-positive and
      negative bacteria, which are recognized by Toll-like receptor (TLR) 2 and 4,
      respectively. Activation of these TLRs initiates multiple pathways that
      subsequently lead to effective immune response. Although, both the TLRs share
      common signaling mechanism yet they may exhibit specificity as well, resulting in
      the release of diverse range of inflammatory mediators which could be used as
      candidate biomolecules for bacterial infections. RESULTS: We adopted systems
      biological approach to identify signaling pathways mediated by TLRs to determine
      candidate molecules associated with bacterial infections. We used bioinformatics
      concepts, including literature mining to construct protein-protein interaction
      network, prioritization of TLRs specific nodes using microarray data and pathway
      analysis. Our constructed PPI network for TLR 2 (nodes: 4091 and edges: 66068)
      and TLR 4 (node: 4076 and edges: 67898) showed 3207 common nodes, indicating that
      both the TLRs might share similar signaling events that are attributed to cell
      migration, MAPK pathway and several inflammatory cascades. Our results propose
      the potential collaboration between the shared signaling pathways of both the
      receptors may enhance the immune response against invading pathogens. Further, to
      identify candidate molecules, the TLRs specific nodes were prioritized using
      microarray differential expressed genes. Of the top prioritized TLR 2 molecules,
      70% were co-expressed. A similar trend was also observed within TLR 4 nodes.
      Further, most of these molecules were preferentially found in blood plasma for
      feasible diagnosis. CONCLUSIONS: The analysis reveals the common and unique
      mechanism regulated by both the TLRs that provide a broad perspective of
      signaling events in bacterial infections. Further, the identified candidate
      biomolecules could potentially aid future research efforts concerning the
      possibility in differential diagnosis of gram-positive and negative bacterial
      infections.

PMID- 24587174
TI  - Sign language ability in young deaf signers predicts comprehension of written
      sentences in English.
AB  - We investigated the robust correlation between American Sign Language (ASL) and
      English reading ability in 51 young deaf signers ages 7;3 to 19;0. Signers were
      divided into 'skilled' and 'less-skilled' signer groups based on their
      performance on three measures of ASL. We next assessed reading comprehension of
      four English sentence structures (actives, passives, pronouns, reflexive
      pronouns) using a sentence-to-picture-matching task. Of interest was the extent
      to which ASL proficiency provided a foundation for lexical and syntactic
      processes of English. Skilled signers outperformed less-skilled signers overall.
      Error analyses further indicated greater single-word recognition difficulties in
      less-skilled signers marked by a higher rate of errors reflecting an inability to
      identify the actors and actions described in the sentence. Our findings provide
      evidence that increased ASL ability supports English sentence comprehension both
      at the levels of individual words and syntax. This is consistent with the theory
      that first language learning promotes second language through transference of
      linguistic elements irrespective of the transparency of mapping of grammatical
      structures between the two languages. 

PMID- 24587175
TI  - Autaptic connections and synaptic depression constrain and promote gamma
      oscillations.
AB  - Computational models of gamma oscillations have helped increase our understanding
      of the mechanisms that shape these 40-80 Hz cortical rhythms. Evidence suggests
      that interneurons known as basket cells are responsible for the generation of
      gamma oscillations. However, current models of gamma oscillations lack the
      dynamic short term synaptic plasticity seen at basket cell-basket cell synapses
      as well as the large autaptic synapses basket cells are known to express. Hence,
      I sought to extend the Wang-Buzsaki model of gamma oscillations to include these
      features. I found that autapses increased the synchrony of basket cell membrane
      potentials across the network during neocortical gamma oscillations as well as
      allowed the network to oscillate over a broader range of depolarizing drive. I
      also found that including realistic synaptic depression filtered the output of
      the network. Depression restricted the network to oscillate in the 60-80 Hz range
      rather than the 40-120 Hz range seen in the standard model. This work shows the
      importance of including accurate synapses in any future model of gamma
      oscillations. 

PMID- 24587176
TI  - RNF8-independent Lys63 poly-ubiquitylation prevents genomic instability in
      response to replication-associated DNA damage.
AB  - The cellular response to DNA double strand breaks (DSBs) involves the ordered
      assembly of repair proteins at or near sites of damage. This process is mediated
      through post-translational protein modifications that include both
      phosphorylation and ubiquitylation. Recent data have demonstrated that
      recruitment of the repair proteins BRCA1, 53BP1, and RAD18 to ionizing
      irradiation (IR) induced DSBs is dependent on formation of non-canonical K63
      linked polyubiquitin chains by the RNF8 and RNF168 ubiquitin ligases. Here we
      report a novel role for K63-ubiquitylation in response to replication-associated
      DSBs that contributes to both cell survival and maintenance of genome stability.
      Suppression of K63-ubiquitylation markedly increases large-scale mutations and
      chromosomal aberrations in response to endogenous or exogenous replication
      associated DSBs. These effects are associated with an S-phase specific defect in
      DNA repair as revealed by an increase in residual 53BP1 foci. Use of both
      knockdown and knockout cell lines indicates that unlike the case for IR-induced
      DSBs, the requirement for K63-ubiquitylation for the repair of replication
      associated DSBs was found to be RNF8-independent. Our findings reveal the
      existence of a novel K63-ubiquitylation dependent repair pathway that contributes
      to the maintenance of genome integrity in response to replication-associated
      DSBs. 

PMID- 24587177
TI  - Serotonin, dopamine and noradrenaline adjust actions of myelinated afferents via
      modulation of presynaptic inhibition in the mouse spinal cord.
AB  - Gain control of primary afferent neurotransmission at their intraspinal terminals
      occurs by several mechanisms including primary afferent depolarization (PAD). PAD
      produces presynaptic inhibition via a reduction in transmitter release. While it
      is known that descending monoaminergic pathways complexly regulate sensory
      processing, the extent these actions include modulation of afferent-evoked PAD
      remains uncertain. We investigated the effects of serotonin (5HT), dopamine (DA)
      and noradrenaline (NA) on afferent transmission and PAD. Responses were evoked by
      stimulation of myelinated hindlimb cutaneous and muscle afferents in the isolated
      neonatal mouse spinal cord. Monosynaptic responses were examined in the deep
      dorsal horn either as population excitatory synaptic responses (recorded as
      extracellular field potentials; EFPs) or intracellular excitatory postsynaptic
      currents (EPSCs). The magnitude of PAD generated intraspinally was estimated from
      electrotonically back-propagating dorsal root potentials (DRPs) recorded on
      lumbar dorsal roots. 5HT depressed the DRP by 76%. Monosynaptic actions were
      similarly depressed by 5HT (EFPs 54%; EPSCs 75%) but with a slower time course.
      This suggests that depression of monosynaptic EFPs and DRPs occurs by independent
      mechanisms. DA and NA had similar depressant actions on DRPs but weaker effects
      on EFPs. IC50 values for DRP depression were 0.6, 0.8 and 1.0 uM for 5HT, DA and
      NA, respectively. Depression of DRPs by monoamines was nearly-identical in both
      muscle and cutaneous afferent-evoked responses, supporting a global modulation of
      the multimodal afferents stimulated. 5HT, DA and NA produced no change in the
      compound antidromic potentials evoked by intraspinal microstimulation indicating
      that depression of the DRP is unrelated to direct changes in the excitability of
      intraspinal afferent fibers, but due to metabotropic receptor activation. In
      summary, both myelinated afferent-evoked DRPs and monosynaptic transmission in
      the dorsal horn are broadly reduced by descending monoamine transmitters. These
      actions likely integrate with modulatory actions elsewhere to reconfigure spinal
      circuits during motor behaviors. 

PMID- 24587178
TI  - Electroacupuncture promotes post-stroke functional recovery via enhancing
      endogenous neurogenesis in mouse focal cerebral ischemia.
AB  - To investigate the question of whether electroacupuncture (EA) promotes
      functional recovery via enhancement of proliferation and differentiation of
      neuronal stem cells (NSCs) in ischemic stroke, EA stimulation with 2 Hz was
      applied at bilateral acupoints to Baihui (GV20) and Dazhui (GV14) in middle
      cerebral artery occlusion (MCAO) mice. EA stimulation improved neuromotor
      function and cognitive ability after ischemic stroke. EA stimulation resulted in
      an increase in the number of proliferated cells, especially in the subventricular
      zone (SVZ) of the ipsilateral hemisphere. Although a very limited number of NSCs
      survived and differentiated into neurons or astrocytes, EA treatment resulted in
      a significant increase in the number of proliferative cells and differentiated
      cells in the hippocampus and SVZ of the ipsilateral hemisphere compared to MCAO
      mice. EA stimulation resulted in significantly increased mRNA expression of brain
      derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF).
      Protein levels of these factors were confirmed in the ipsilateral hippocampus and
      SVZ by immunohistochemical and Western blotting analyses. Expression of
      phosphorylated phosphatidylinositol-3-kinase, BDNF, and VEGF-mediated down-stream
      were enhanced by EA stimulation in newly formed neuroblasts. These results
      indicate that EA treatment after ischemic stroke may promote post-stroke
      functional recovery by enhancement of proliferation and differentiation of NSCs
      via the BDNF and VEGF signaling pathway. 

PMID- 24587179
TI  - Comparative genomic and transcriptomic analyses of LNCaP and C4-2B prostate
      cancer cell lines.
AB  - The LNCaP and C4-2B cell lines form an excellent preclinical model to study the
      development of metastatic castration-resistant prostate cancer, since C4-2B cells
      were derived from a bone metastasis that grew in nude mice after inoculation with
      the LNCaP-derived, castration-resistant C4-2 cells. Exome sequencing detected
      2188 and 3840 mutations in LNCaP and C4-2B cells, respectively, of which 1784
      were found in both cell lines. Surprisingly, the parental LNCaP cells have over
      400 mutations that were not found in the C4-2B genome. More than half of the
      mutations found in the exomes were confirmed by analyzing the RNA-seq data, and
      we observed that the expressed genes are more prone to mutations than non
      expressed genes. The transcriptomes also revealed that 457 genes show increased
      expression and 246 genes show decreased expression in C4-2B compared to LNCaP
      cells. By combining the list of C4-2B-specific mutations with the list of
      differentially expressed genes, we detected important changes in the focal
      adhesion and ECM-receptor interaction pathways. Integration of these pathways
      converges on the myosin light chain kinase gene (MLCK) which might contribute to
      the metastatic potential of C4-2B cells. In conclusion, we provide extensive
      databases for mutated genes and differentially expressed genes in the LNCaP and
      C4-2B prostate cancer cell lines. These can be useful for other researchers using
      these cell models. 

PMID- 24587180
TI  - Evolution and structural organization of the C proteins of paramyxovirinae.
AB  - The phosphoprotein (P) gene of most Paramyxovirinae encodes several proteins in
      overlapping frames: P and V, which share a common N-terminus (PNT), and C, which
      overlaps PNT. Overlapping genes are of particular interest because they encode
      proteins originated de novo, some of which have unknown structural folds,
      challenging the notion that nature utilizes only a limited, well-mapped area of
      fold space. The C proteins cluster in three groups, comprising measles, Nipah,
      and Sendai virus. We predicted that all C proteins have a similar organization: a
      variable, disordered N-terminus and a conserved, alpha-helical C-terminus. We
      confirmed this predicted organization by biophysically characterizing recombinant
      C proteins from Tupaia paramyxovirus (measles group) and human parainfluenza
      virus 1 (Sendai group). We also found that the C of the measles and Nipah groups
      have statistically significant sequence similarity, indicating a common origin.
      Although the C of the Sendai group lack sequence similarity with them, we
      speculate that they also have a common origin, given their similar genomic
      location and structural organization. Since C is dispensable for viral
      replication, unlike PNT, we hypothesize that C may have originated de novo by
      overprinting PNT in the ancestor of Paramyxovirinae. Intriguingly, in measles
      virus and Nipah virus, PNT encodes STAT1-binding sites that overlap different
      regions of the C-terminus of C, indicating they have probably originated
      independently. This arrangement, in which the same genetic region encodes
      simultaneously a crucial functional motif (a STAT1-binding site) and a highly
      constrained region (the C-terminus of C), seems paradoxical, since it should
      severely reduce the ability of the virus to adapt. The fact that it originated
      twice suggests that it must be balanced by an evolutionary advantage, perhaps
      from reducing the size of the genetic region vulnerable to mutations. 

PMID- 24587181
TI  - Syntaxin 1B, but not syntaxin 1A, is necessary for the regulation of synaptic
      vesicle exocytosis and of the readily releasable pool at central synapses.
AB  - Two syntaxin 1 (STX1) isoforms, HPC-1/STX1A and STX1B, are coexpressed in neurons
      and function as neuronal target membrane (t)-SNAREs. However, little is known
      about their functional differences in synaptic transmission. STX1A null mutant
      mice develop normally and do not show abnormalities in fast synaptic
      transmission, but monoaminergic transmissions are impaired. In the present study,
      we found that STX1B null mutant mice died within 2 weeks of birth. To examine
      functional differences between STX1A and 1B, we analyzed the presynaptic
      properties of glutamatergic and GABAergic synapses in STX1B null mutant and
      STX1A/1B double null mutant mice. We found that the frequency of spontaneous
      quantal release was lower and the paired-pulse ratio of evoked postsynaptic
      currents was significantly greater in glutamatergic and GABAergic synapses of
      STX1B null neurons. Deletion of STX1B also accelerated synaptic vesicle turnover
      in glutamatergic synapses and decreased the size of the readily releasable pool
      in glutamatergic and GABAergic synapses. Moreover, STX1A/1B double null neurons
      showed reduced and asynchronous evoked synaptic vesicle release in glutamatergic
      and GABAergic synapses. Our results suggest that although STX1A and 1B share a
      basic function as neuronal t-SNAREs, STX1B but not STX1A is necessary for the
      regulation of spontaneous and evoked synaptic vesicle exocytosis in fast
      transmission. 

PMID- 24587182
TI  - In vivo activity of miR-34a mimics delivered by stable nucleic acid lipid
      particles (SNALPs) against multiple myeloma.
AB  - Multiple myeloma (MM) is a disease with an adverse outcome and new therapeutic
      strategies are urgently awaited. A rising body of evidence supports the notion
      that microRNAs (miRNAs), master regulators of eukaryotic gene expression, may
      exert anti-MM activity. Here, we evaluated the activity of synthetic miR-34a in
      MM cells. We found that transfection of miR-34a mimics in MM cells induces a
      significant change of gene expression with relevant effects on multiple signal
      transduction pathways. We detected early inactivation of pro-survival and
      proliferative kinases Erk-2 and Akt followed at later time points by caspase-6
      and -3 activation and apoptosis induction. To improve the in vivo delivery, we
      encapsulated miR-34a mimics in stable nucleic acid lipid particles (SNALPs). We
      found that SNALPs miR-34a were highly efficient in vitro in inhibiting growth of
      MM cells. Then, we investigated the activity of the SNALPs miR-34a against MM
      xenografts in SCID mice. We observed significant tumor growth inhibition (p<0.05)
      which translated in mice survival benefits (p=0.0047). Analysis of miR-34a and
      NOTCH1 expression in tumor retrieved from animal demonstrated efficient delivery
      and gene modulation induced by SNALPs miR-34a in the absence of systemic
      toxicity. We here therefore provide evidence that SNALPs miR-34a may represent a
      promising tool for miRNA-therapeutics in MM.

PMID- 24587183
TI  - Clonal, self-renewing and differentiating human and porcine urothelial cells, a
      novel stem cell population.
AB  - Although urothelial progenitor-like cells have been described in the human
      urinary tract, the existence of stem cells remains to be proven. Using a culture
      system that favors clonogenic epithelial cell growth, we evaluated and
      characterized clonal human urothelial cells. We isolated human urothelial cells
      that were clonogenic, capable of self-renewal and could develop into fully
      differentiated urothelium once re-implanted into the subcapsular space of nude
      mice. In addition to final urothelial cell differentiation, spontaneous formation
      of bladder-like microstructures was observed. By examining an epithelial stem
      cell signature marker, we found p63 to correlate with the self-renewal capacity
      of the isolated human urothelial clonal populations. Since a clinically relevant,
      long-term model for functional reconstitution of human cells does not exist, we
      sought to establish a culture method for porcine urothelial cells in a clinically
      relevant porcine model. We isolated cells from porcine ureter, urethra and
      bladder that were clonogenic and capable of self-renewal and differentiation into
      fully mature urothelium. In conclusion, we could isolate human and porcine cell
      populations, behaving as urothelial stem cells and showing clonogenicity, self
      renewal and, once re-implanted, morphological differentiation. 

PMID- 24587184
TI  - Evaluation of the dosimetric feasibility of hippocampal sparing intensity
      modulated radiotherapy in patients with locally advanced nasopharyngeal
      carcinoma.
AB  - PURPOSE: The objective of this study was to evaluate the dosimetric feasibility
      of using hippocampus (HPC) sparing intensity-modulated radiotherapy (IMRT) in
      patients with locally advanced nasopharyngeal carcinoma (NPC). MATERIALS/METHODS:
      Eight cases of either T3 or T4 NPC were selected for this study. Standard IMRT
      treatment plans were constructed using the volume and dose constraints for the
      targets and organs at risk (OAR) per Radiation Therapy Oncology Group (RTOG) 0615
      protocol. Experimental plans were constructed using the same criteria, with the
      addition of the HPC as an OAR. The two dose-volume histograms for each case were
      compared for the targets and OARs. RESULTS: All plans achieved the protocol dose
      criteria. The homogeneity index, conformity index, and coverage index for the
      planning target volumes (PTVs) were not significantly compromised by the
      avoidance of the HPC. The doses to all OARs, excluding the HPC, were similar.
      Both the dose (Dmax, D2%, D40%, D mean, D median, D98% and D min) and volume (V5,
      V10, V15, V20, V30, V40 and V50) parameters for the HPC were significantly lower
      in the HPC sparing plans (p<0.05), except for D min (P = 0.06) and V5 (P = 0.12).
      CONCLUSIONS: IMRT for patients with locally advanced NPC exposes the HPC to a
      significant radiation dose. HPC sparing IMRT planning significantly decreases
      this dose, with minimal impact on the therapeutic targets and other OARs.

PMID- 24587185
TI  - Circulating Ang-2 mRNA expression levels: looking ahead to a new prognostic
      factor for NSCLC [corrected].
AB  - Non-small cell lung cancer (NSCLC) is the most common cancer and the leading
      cause of death from cancer worldwide. Antiangiogenic strategies directed towards
      tumor stroma are becoming gold standard in NSCLC treatment and researchers have
      been searching for biomarkers to identify patients for whom therapy with
      antiangiogenic inhibitors may be most beneficial and the importance of these as
      prognostic factors in NSCLC. The purpose of this study was to evaluate the
      prognostic value of circulating Ang-2 mRNA levels prior to treatment in NSCLC
      patients. The mRNA levels were determined by quantitative real-time PCR in the
      peripheral blood of 92 NSCLC patients. Our results demonstrate that patients with
      high circulating Ang-2 mRNA levels have diminished overall survival when compared
      to those with low mRNA levels (20.3 months vs 34.3 months, respectively; Log Rank
      Test, p = 0.016), when considering all NSCLC stages and this difference is even
      bigger when considering only patients with stage IV (15.9 months vs 31.3 months,
      respectively; Log Rank Test, p = 0.036). Moreover, circulating Ang-2 mRNA levels
      independently determine overall survival, and the concordance (c) index analysis
      showed that the definition of a nomogram that contains information regarding
      tumor stage, patients' smoking status and circulating Ang-2 mRNA levels present
      an increased capacity to predict overall survival in NSCLC patients (c-index
      0.798). These results suggest that this nomogram could serve as a unique and
      practical tool to determine prognosis in NSCLC, not relying on the availability
      of adequate surgical or biopsy specimens of NSCLC. Attending to our results, the
      circulating Ang-2 mRNA levels should also be included in the design of
      preclinical studies and clinical trials involving antiangiogenic drugs targeting
      Ang-2, to guide adequate patient stratification and dose selection and increasing
      the likelihood of benefit to a level that is acceptable to patients and
      clinicians.

PMID- 24587186
TI  - Changes in selection regime cause loss of phenotypic plasticity in planktonic
      freshwater copepods.
AB  - Rapid phenotypic adaptation is critical for populations facing environmental
      changes and can be facilitated by phenotypic plasticity in the selected traits.
      Whereas recurrent environmental fluctuations can favour the maintenance or de
      novo evolution of plasticity, strong selection is hypothesized to decrease
      plasticity or even fix the trait (genetic assimilation). Despite advances in the
      theoretical understanding of the impact of plasticity on diversification
      processes, comparatively little empirical data of populations undergoing
      diversification mediated by plasticity are available. Here we use the planktonic
      freshwater copepod Acanthodiaptomus denticornis from two lakes as model system to
      study UV stress responses of two phenotypically different populations under
      laboratory conditions. Our study reveals heritable lake- and sex-specific
      differences of behaviour, physiological plasticity, and mortality. We discuss
      specific selective scenarios causing these differences and argue that phenotypic
      plasticity will be higher when selection pressure is moderate, but will decrease
      or even be lost under stronger pressure. 

PMID- 24587187
TI  - A retrospective study of chronic post-surgical pain following thoracic surgery:
      prevalence, risk factors, incidence of neuropathic component, and impact on
      qualify of life.
AB  - BACKGROUND: Thoracic surgeries including thoracotomy and VATS are some of the
      highest risk procedures that often lead to CPSP, with or without a neuropathic
      component. This retrospective study aims to determine retrospectively the
      prevalence of CPSP following thoracic surgery, its predicting risk factors, the
      incidence of neuropathic component, and its impact on quality of life. METHODS:
      Patients who underwent thoracic surgeries including thoracotomy and VATS between
      01/2010 and 12/2011 at the First Affiliated Hospital, School of Medicine,
      Zhejiang University were first contacted and screened for CPSP following thoracic
      surgery via phone interview. Patients who developed CPSP were then mailed with a
      battery of questionnaires, including a questionnaire referenced to Maguire's
      research, a validated Chinese version of the ID pain questionnaire, and a SF-36
      Health Survey. Logistic regression analyses were subsequently performed to
      identify risk factors for CPSP following thoracic surgery and its neuropathic
      component. RESULTS: The point prevalence of CPSP following thoracic surgery was
      24.9% (320/1284 patients), and the point prevalence of neuropathic component of
      CPSP was 32.5% (86/265 patients). CPSP following thoracic surgery did not improve
      significantly with time. Multiple predictive factors were identified for CPSP
      following thoracic surgery, including age<60 years old, female gender, prolonged
      duration of post-operative chest tube drainage (>= 4 days), options of post
      operative pain management, and pre-existing hypertension. Furthermore, patients
      who experienced CPSP following thoracic surgery were found to have significantly
      decreased physical function and worse quality of life, especially those with
      neuropathic component. CONCLUSIONS: Our study demonstrated that nearly 1 out of 4
      patients underwent thoracic surgery might develop CPSP, and one third of them
      accompanied with a neuropathic component. Early prevention as well as aggressive
      treatment is important for patients with CPSP following thoracic surgery to
      achieve a high quality of life.

PMID- 24587188
TI  - Impact of different creatinine measurement methods on liver transplant
      allocation.
AB  - INTRODUCTION: The model for end-stage liver disease (MELD) score is used in many
      countries to prioritize organ allocation for the majority of patients who require
      orthotopic liver transplantation. This score is calculated based on the following
      laboratory parameters: creatinine, bilirubin and the international normalized
      ratio (INR). Consequently, high measurement accuracy is essential for equitable
      and fair organ allocation. For serum creatinine measurements, the Jaffe method
      and enzymatic detection are well-established routine diagnostic tests. METHODS: A
      total of 1,013 samples from 445 patients on the waiting list or in evaluation for
      liver transplantation were measured using both creatinine methods from November
      2012 to September 2013 at the university hospital Leipzig, Germany. The
      measurements were performed in parallel according to the manufacturer's
      instructions after the samples arrived at the institute of laboratory medicine.
      Patients who had required renal replacement therapy twice in the previous week
      were excluded from analyses. RESULTS: Despite the good correlation between the
      results of both creatinine quantification methods, relevant differences were
      observed, which led to different MELD scores. The Jaffe measurement led to
      greater MELD score in 163/1,013 (16.1%) samples with differences of up to 4
      points in one patient, whereas differences of up to 2 points were identified in
      15/1,013 (1.5%) samples using the enzymatic assay. Overall, 50/152 (32.9%)
      patients with MELD scores >20 had higher scores when the Jaffe method was used.
      DISCUSSION: Using the Jaffe method to measure creatinine levels in samples from
      patients who require liver transplantation may lead to a systematic preference in
      organ allocation. In this study, the differences were particularly pronounced in
      samples with MELD scores >20, which has clinical relevance in the context of
      urgency of transplantation. These data suggest that official recommendations are
      needed to determine which laboratory diagnostic methods should be used when
      calculating MELD scores.

PMID- 24587189
TI  - CB1 blockade potentiates down-regulation of lipogenic gene expression in
      perirenal adipose tissue in high carbohydrate diet-induced obesity.
AB  - De novo lipogenesis and hypercaloric diets are thought to contribute to increased
      fat mass, particularly in abdominal fat depots. CB1 is highly expressed in
      adipose tissue, and CB1-mediated signalling is associated with stimulation of
      lipogenesis and diet-induced obesity, though its contribution to increasing fat
      deposition in adipose tissue is controversial. Lipogenesis is regulated by
      transcription factors such as liver X receptor (LXR), sterol-response element
      binding protein (SREBP) and carbohydrate-responsive-element-binding protein
      (ChREBP). We evaluated the role of CB1 in the gene expression of these factors
      and their target genes in relation to lipogenesis in the perirenal adipose tissue
      (PrAT) of rats fed a high-carbohydrate diet (HCHD) or a high-fat diet (HFD). Both
      obesity models showed an up-regulated gene expression of CB1 and Lxralpha in this
      adipose pad. The Srebf-1 and ChREBP gene expressions were down-regulated in HFD
      but not in HCHD. The expression of their target genes encoding for lipogenic
      enzymes showed a decrease in diet-induced obesity and was particularly dramatic
      in HFD. In HCHD, CB1 blockade by AM251 reduced the Srebf-1 and ChREBP expression
      and totally abrogated the remnant gene expression of their target lipogenic
      enzymes. The phosphorylated form of the extracellular signal-regulated kinase
      (ERK-p), which participates in the CB1-mediated signalling pathway, was markedly
      present in the PrAT of obese rats. ERK-p was drastically repressed by AM251
      indicating that CB1 is actually functional in PrAT of obese animals, though its
      activation loses the ability to stimulate lipogenesis in PrAT of obese rats. Even
      so, the remnant expression levels of lipogenic transcription factors found in
      HCHD-fed rats are still dependent on CB1 activity. Hence, in HCHD-induced
      obesity, CB1 blockade may help to further potentiate the reduction of lipogenesis
      in PrAT by means of inducing down-regulation of the ChREBP and Srebf-1 gene
      expression, and consequently in the expression of lipogenic enzymes. 

PMID- 24587190
TI  - Non-invasive optical imaging of eosinophilia during the course of an experimental
      allergic airways disease model and in response to therapy.
AB  - BACKGROUND: Molecular imaging of lung diseases, including asthma, is limited and
      either invasive or non-specific. Central to the inflammatory process in asthma is
      the recruitment of eosinophils to the airways, which release proteases and
      proinflammatory factors and contribute to airway remodeling. The aim of this
      study was to establish a new approach to non-invasively assess lung eosinophilia
      during the course of experimental asthma by combining non-invasive near-infrared
      fluorescence (NIRF) imaging with the specific detection of Siglec-F, a lectin
      found predominantly on eosinophils. METHODOLOGY/PRINCIPAL FINDINGS: An ovalbumin
      (OVA)-based model was used to induce asthma-like experimental allergic airway
      disease (EAAD) in BALB/c mice. By means of a NIRF imager, we demonstrate that 48
      h-72 h after intravenous (i.v.) application of a NIRF-labeled anti-Siglec-F
      antibody, mice with EAAD exhibited up to 2 times higher fluorescence intensities
      compared to lungs of control mice. Furthermore, average lung intensities of
      dexamethasone-treated as well as beta-escin-treated mice were 1.8 and 2 times
      lower than those of untreated, EAAD mice, respectively and correlated with the
      reduction of cell infiltration in the lung. Average fluorescence intensities
      measured in explanted lungs confirmed the in vivo findings of significantly
      higher values in inflamed lungs as compared to controls. Fluorescence microscopy
      of lung cryosections localized the i.v. applied NIRF-labeled anti-Siglec-F
      antibody predominantly to eosinophils in the peribronchial areas of EAAD lungs as
      opposed to control lungs. CONCLUSION/SIGNIFICANCE: We show that monitoring the
      occurrence of eosinophils, a prominent feature of allergic asthma, by means of a
      NIRF-labeled antibody directed against Siglec-F is a novel and powerful non
      invasive optical imaging approach to assess EAAD and therapeutic response in mice
      over time.

PMID- 24587191
TI  - Elevated exhaled nitric oxide in allergen-provoked asthma is associated with
      airway epithelial iNOS.
AB  - BACKGROUND: Fractional exhaled nitric oxide is elevated in allergen-provoked
      asthma. The cellular and molecular source of the elevated fractional exhaled
      nitric oxide is, however, uncertain. OBJECTIVE: To investigate whether fractional
      exhaled nitric oxide is associated with increased airway epithelial inducible
      nitric oxide synthase (iNOS) in allergen-provoked asthma. METHODS: Fractional
      exhaled nitric oxide was measured in healthy controls (n = 14) and allergic
      asthmatics (n = 12), before and after bronchial provocation to birch pollen out
      of season. Bronchoscopy was performed before and 24 hours after allergen
      provocation. Bronchial biopsies and brush biopsies were processed for nitric
      oxide synthase activity staining with nicotinamide adenine dinucleotide phosphate
      diaphorase (NADPH-d), iNOS immunostaining, or gene expression analysis of iNOS by
      real-time PCR. NADPH-d and iNOS staining were quantified using automated
      morphometric analysis. RESULTS: Fractional exhaled nitric oxide and expression of
      iNOS mRNA were significantly higher in un-provoked asthmatics, compared to
      healthy controls. Allergic asthmatics exhibited a significant elevation of
      fractional exhaled nitric oxide after allergen provocation, as well as an
      accumulation of airway eosinophils. Moreover, nitric oxide synthase activity and
      expression of iNOS was significantly increased in the bronchial epithelium of
      asthmatics following allergen provocation. Fractional exhaled nitric oxide
      correlated with eosinophils and iNOS expression. CONCLUSION: Higher fractional
      exhaled nitric oxide concentration among asthmatics is associated with elevated
      iNOS mRNA in the bronchial epithelium. Furthermore, our data demonstrates for the
      first time increased expression and activity of iNOS in the bronchial epithelium
      after allergen provocation, and thus provide a mechanistic explanation for
      elevated fractional exhaled nitric oxide in allergen-provoked asthma.

PMID- 24587192
TI  - Syncytiotrophoblast vesicles show altered micro-RNA and haemoglobin content after
      ex-vivo perfusion of placentas with haemoglobin to mimic preeclampsia.
AB  - BACKGROUND: Cell-free foetal haemoglobin (HbF) has been shown to play a role in
      the pathology of preeclampsia (PE). In the present study, we aimed to further
      characterize the harmful effects of extracellular free haemoglobin (Hb) on the
      placenta. In particular, we investigated whether cell-free Hb affects the release
      of placental syncytiotrophoblast vesicles (STBMs) and their micro-RNA content.
      METHODS: The dual ex-vivo perfusion system was used to perfuse isolated
      cotyledons from human placenta, with medium alone (control) or supplemented with
      cell-free Hb. Perfusion medium from the maternal side of the placenta was
      collected at the end of all perfusion phases. The STBMs were isolated using ultra
      centrifugation, at 10,000*g and 150,000*g (referred to as 10K and 150K STBMs).
      The STBMs were characterized using the nanoparticle tracking analysis,
      identification of surface markers and transmission electron microscopy. RNA was
      extracted and nine different micro-RNAs, related to hypoxia, PE and Hb synthesis,
      were selected for analysis by quantitative PCR. RESULTS: All micro-RNAs
      investigated were present in the STBMs. Mir-517a, mir-141 and mir-517b were down
      regulated after Hb perfusion in the 10K STBMs. Furthermore, Hb was shown to be
      carried by the STBMs. CONCLUSION: This study showed that Hb perfusion can alter
      the micro-RNA content of released STBMs. Of particular interest is the alteration
      of two placenta specific micro-RNAs; mir-517a and mir-517b. We have also seen
      that STBMs may function as carriers of Hb into the maternal circulation.

PMID- 24587193
TI  - Triage of HR-HPV positive women with minor cytological abnormalities: a
      comparison of mRNA testing, HPV DNA testing, and repeat cytology using a 4-year
      follow-up of a population-based study.
AB  - OBJECTIVE: Expression of the viral E6/E7 oncogenes of high-risk human
      papillomaviruses (HR-HPV) is necessary for malignant conversion and maintenance
      in cervical tissue. In order to determine whether HR-HPV E6/E7 mRNA testing more
      effectively predicts precancerous lesions and invasive cervical cancer than HR
      HPV DNA testing, we aimed to compare triage using HR-HPV E6/E7 mRNA testing by
      APTIMA HPV Assay (APTIMA) to HPV16 DNA testing, HPV16/18 DNA testing, and repeat
      cytology. METHODS: Liquid-based (PreservCyt) cell samples were obtained from HR
      HPV-positive women diagnosed with atypical squamous cells of undetermined
      significance (ASCUS) and low-grade squamous intraepithelial lesions (LSIL) within
      the framework of the population-based cervical cancer screening program in
      Stockholm, Sweden. Samples were tested for HR-HPV E6/E7 mRNA by APTIMA (Gene
      Probe Inc., San Diego, CA, USA). Women were followed up for 4 years after the
      index cytology via medical and laboratory records, and the Stockholm Oncology
      Center. RESULTS: Nine of 25 (36%) women in the ASCUS group, and 64 of 180 (36%)
      women in the LSIL group developed cervical intraepithelial neoplasia (CIN) grade
      2 or worse during 4 years of follow-up. 162 (74%) women were APTIMA-positive, and
      APTIMA had the highest sensitivity to predict CIN2 or worse and CIN3 or worse in
      the ASCUS (77.8% and 100%) and LSIL (78.1 and 75.8%) groups, although specificity
      was insufficient (<50%). HPV16 DNA testing and repeat cytology were more specific
      than APTIMA. CONCLUSION: The results of this population-based study with
      comprehensive follow-up support the use of APTIMA as a triage test for women with
      ASCUS. More focused investigation is required for women with LSIL.

PMID- 24587195
TI  - Identification of the protein kinases Pyk3 and Phg2 as regulators of the STATc
      mediated response to hyperosmolarity.
AB  - Cellular adaptation to changes in environmental osmolarity is crucial for cell
      survival. In Dictyostelium, STATc is a key regulator of the transcriptional
      response to hyperosmotic stress. Its phosphorylation and consequent activation is
      controlled by two signaling branches, one cGMP- and the other Ca(2+)-dependent,
      of which many signaling components have yet to be identified. The STATc stress
      signalling pathway feeds back on itself by upregulating the expression of STATc
      and STATc-regulated genes. Based on microarray studies we chose two tyrosine
      kinase like proteins, Pyk3 and Phg2, as possible modulators of STATc
      phosphorylation and generated single and double knock-out mutants to them.
      Transcriptional regulation of STATc and STATc dependent genes was disturbed in
      pyk3(-), phg2(-), and pyk3(-)/phg2(-) cells. The absence of Pyk3 and/or Phg2
      resulted in diminished or completely abolished increased transcription of STATc
      dependent genes in response to sorbitol, 8-Br-cGMP and the Ca(2+) liberator BHQ.
      Also, phospho-STATc levels were significantly reduced in pyk3(-) and phg2(-)
      cells and even further decreased in pyk3(-)/phg2(-) cells. The reduced
      phosphorylation was mirrored by a significant delay in nuclear translocation of
      GFP-STATc. The protein tyrosine phosphatase 3 (PTP3), which dephosphorylates and
      inhibits STATc, is inhibited by stress-induced phosphorylation on S448 and S747.
      Use of phosphoserine specific antibodies showed that Phg2 but not Pyk3 is
      involved in the phosphorylation of PTP3 on S747. In pull-down assays Phg2 and
      PTP3 interact directly, suggesting that Phg2 phosphorylates PTP3 on S747 in vivo.
      Phosphorylation of S448 was unchanged in phg2(-) cells. We show that Phg2 and an,
      as yet unknown, S448 protein kinase are responsible for PTP3 phosphorylation and
      hence its inhibition, and that Pyk3 is involved in the regulation of STATc by
      either directly or indirectly activating it. Our results add further complexities
      to the regulation of STATc, which presumably ensure its optimal activation in
      response to different environmental cues. 

PMID- 24587194
TI  - Regulation of hERG and hEAG channels by Src and by SHP-1 tyrosine phosphatase via
      an ITIM region in the cyclic nucleotide binding domain.
AB  - Members of the EAG K(+) channel superfamily (EAG/Kv10.x, ERG/Kv11.x, ELK/Kv12.x
      subfamilies) are expressed in many cells and tissues. In particular, two
      prototypes, EAG1/Kv10.1/KCNH1 and ERG1/Kv11.1/KCNH2 contribute to both normal and
      pathological functions. Proliferation of numerous cancer cells depends on hEAG1,
      and in some cases, hERG. hERG is best known for contributing to the cardiac
      action potential, and for numerous channel mutations that underlie 'long-QT
      syndrome'. Many cells, particularly cancer cells, express Src-family tyrosine
      kinases and SHP tyrosine phosphatases; and an imbalance in tyrosine
      phosphorylation can lead to malignancies, autoimmune diseases, and inflammatory
      disorders. Ion channel contributions to cell functions are governed, to a large
      degree, by post-translational modulation, especially phosphorylation. However,
      almost nothing is known about roles of specific tyrosine kinases and phosphatases
      in regulating K(+) channels in the EAG superfamily. First, we show that tyrosine
      kinase inhibitor, PP1, and the selective Src inhibitory peptide, Src40-58, reduce
      the hERG current amplitude, without altering its voltage dependence or kinetics.
      PP1 similarly reduces the hEAG1 current. Surprisingly, an 'immuno-receptor
      tyrosine inhibitory motif' (ITIM) is present within the cyclic nucleotide binding
      domain of all EAG-superfamily members, and is conserved in the human, rat and
      mouse sequences. When tyrosine phosphorylated, this ITIM directly bound to and
      activated SHP-1 tyrosine phosphatase (PTP-1C/PTPN6/HCP); the first report that a
      portion of an ion channel is a binding site and activator of a tyrosine
      phosphatase. Both hERG and hEAG1 currents were decreased by applying active
      recombinant SHP-1, and increased by the inhibitory substrate-trapping SHP-1
      mutant. Thus, hERG and hEAG1 currents are regulated by activated SHP-1, in a
      manner opposite to their regulation by Src. Given the widespread distribution of
      these channels, Src and SHP-1, this work has broad implications in cell signaling
      that controls survival, proliferation, differentiation, and other ERG1 and EAG1
      functions in many cell types. 

PMID- 24587196
TI  - Fitness costs of thermal reaction norms for wing melanisation in the large white
      butterfly (Pieris brassicae).
AB  - The large white butterfly, Pieris brassicae, shows a seasonal polyphenism of wing
      melanisation, spring individuals being darker than summer individuals. This
      phenotypic plasticity is supposed to be an adaptive response for thermoregulation
      in natural populations. However, the variation in individuals' response, the
      cause of this variation (genetic, non genetic but inheritable or environmental)
      and its relationship with fitness remain poorly known. We tested the
      relationships between thermal reaction norm of wing melanisation and adult
      lifespan as well as female fecundity. Butterflies were reared in cold (18 degrees
      C), moderate (22 degrees C), and hot (26 degrees C) temperatures over three
      generations to investigate variation in adult pigmentation and the effects of
      maternal thermal environment on offspring reaction norms. We found a low
      heritability in wing melanisation (h(2) =0.18). Rearing families had contrasted
      thermal reaction norms. Adult lifespan of males and females from highly plastic
      families was shorter in individuals exposed to hot developmental temperature.
      Also, females from plastic families exhibited lower fecundity. We did not find
      any effect of maternal or grand-maternal developmental temperature on fitness.
      This study provides new evidence on the influence of phenotypic plasticity on
      life history-traits' evolution, a crucial issue in the context of global change.

PMID- 24587197
TI  - Global transcriptome profiles of Italian Mediterranean buffalo embryos with
      normal and retarded growth.
AB  - The transcriptome profiles were compared for buffalo embryos with normal growth
      and embryos with retarded growth on Day 25 after mating. Embryos with retarded
      growth on Day 25 after mating have a reduced likelihood of undergoing attachment
      to the uterine endometrium and establishing a pregnancy. Italian Mediterranean
      buffaloes were mated by AI and on Day 25 underwent trans-rectal ultrasonography
      to ascertain embryo development. Embryos with an embryonic width (EW)>2.7 mm were
      classed as normal embryos and embryos with an EW<2.7 mm were classed as retarded
      embryos. Three buffaloes with embryos of the largest EW (3.7, 3.7 and 3.9 mm) and
      three buffaloes with embryos of the smallest EW (1.5, 1.6 and 1.9 mm) were
      slaughtered on Day 27 to recover embryos for transcriptome analysis using a
      bovine custom designed oligo array. A total of 1,047 transcripts were
      differentially expressed between embryos with normal growth and embryos with
      retarded growth. Retarded embryos showed 773/1,047 (74%) transcripts that were
      down-regulated and 274/1,047 (26%) transcripts that were up-regulated relative to
      normal embryos; in silico analyses focused on 680/1,047 (65%) of the
      differentially expressed transcripts. The most altered transcripts observed in
      retarded embryos were associated with membrane structure and function and with
      metabolic and homeostasis maintenance functions. Other notable functions altered
      in retarded embryos were developmental processes and in particular nervous system
      differentiation and function. Specific biochemical pathways such as the
      complement cascade and coagulation were also altered in retarded embryos. It was
      concluded from the findings that buffalo embryos with retarded growth on Day 25
      after mating show altered gene expression compared with normal embryos, and some
      de-regulated functions are associated with attachment to the uterine endometrium.

PMID- 24587198
TI  - Establishment of real time allele specific locked nucleic acid quantitative PCR
      for detection of HBV YIDD (ATT) mutation and evaluation of its application.
AB  - BACKGROUND: Long-term use of nucleos(t)ide analogues can increase risk of HBV
      drug-resistance mutations. The rtM204I (ATT coding for isoleucine) is one of the
      most important resistance mutation sites. Establishing a simple, rapid, reliable
      and highly sensitive assay to detect the resistant mutants as early as possible
      is of great clinical significance. METHODS: Recombinant plasmids for HBV YMDD
      (tyrosine-methionine-aspartate-aspartate) and YIDD (tyrosine-isoleucine-aspartate
      aspartate) were constructed by TA cloning. Real time allele specific locked
      nucleic acid quantitative PCR (RT-AS-LNA-qPCR) with SYBR Green I was established
      by LNA-modified primers and evaluated with standard recombinant plasmids,
      clinical templates (the clinical wild type and mutant HBV DNA mixture) and 102
      serum samples from nucleos(t)ide analogues-experienced patients. The serum
      samples from a chronic hepatitis B (CHB) patient firstly received LMV mono
      therapy and then switched to LMV + ADV combined therapy were also dynamically
      analyzed for 10 times. RESULTS: The linear range of the assay was between 1*10(9)
      copies/MUl and 1 * 10(2) copies/MUl. The low detection limit was 1 * 10(1)
      copies/MUl. Sensitivity of the assay were 10(-6), 10(-4) and 10(-2) in the wild
      type background of 1 * 10(9) copies/MUl, 1 * 10(7) copies/MUl and 1 * 10(5)
      copies/MUl, respectively. The sensitivity of the assay in detection of clinical
      samples was 0.03%. The complete coincidence rate between RT-AS-LNA-qPCR and
      direct sequencing was 91.2% (93/102), partial coincidence rate was 8.8% (9/102),
      and no complete discordance was observed. The two assays showed a high
      concordance (Kappa = 0.676, P = 0.000). Minor variants can be detected 18 weeks
      earlier than the rebound of HBV DNA load and alanine aminotransferase level.
      CONCLUSIONS: A rapid, cost-effective, high sensitive, specific and reliable
      method of RT-AS-LNA-qPCR with SYBR Green I for early and absolute quantification
      of HBV YIDD (ATT coding for isoleucine) variants was established, which can
      provide valuable information for clinical antiretroviral regimens.

PMID- 24587199
TI  - Post-translational modifications modulate ligand recognition by the third PDZ
      domain of the MAGUK protein PSD-95.
AB  - The relative promiscuity of hub proteins such as postsynaptic density protein-95
      (PSD-95) can be achieved by alternative splicing, allosteric regulation, and post
      translational modifications, the latter of which is the most efficient method of
      accelerating cellular responses to environmental changes in vivo. Here, a
      mutational approach was used to determine the impact of phosphorylation and
      succinimidation post-translational modifications on the binding affinity of the
      postsynaptic density protein-95/discs large/zonula occludens-1 (PDZ3) domain of
      PSD-95. Molecular dynamics simulations revealed that the binding affinity of this
      domain is influenced by an interplay between salt-bridges linking the alpha3
      helix, the beta2-beta3 loop and the positively charged Lys residues in its high
      affinity hexapeptide ligand KKETAV. The alpha3 helix is an extra structural
      element that is not present in other PDZ domains, which links PDZ3 with the
      following SH3 domain in the PSD-95 protein. This regulatory mechanism was
      confirmed experimentally via thermodynamic and NMR chemical shift perturbation
      analyses, discarding intra-domain long-range effects. Taken together, the results
      presented here reveal the molecular basis of the regulatory role of the alpha3
      extra-element and the effects of post-translational modifications of PDZ3 on its
      binding affinity, both energetically and dynamically. 

PMID- 24587200
TI  - Meglumine exerts protective effects against features of metabolic syndrome and
      type II diabetes.
AB  - Metabolic syndrome, diabetes and diabetes complications pose a growing medical
      challenge worldwide, accentuating the need of safe and effective strategies for
      their clinical management. Here we present preclinical evidence that the sorbitol
      derivative meglumine (N-methyl-D-glucamine) can safely protect against several
      features of metabolic syndrome and diabetes, as well as elicit enhancement in
      muscle stamina. Meglumine is a compound routinely used as an approved excipient
      to improve drug absorption that has not been ascribed any direct biological
      effects in vivo. Normal mice (SV129) administered 18 mM meglumine orally for six
      weeks did not display any gastrointestinal or other observable adverse effects,
      but had a marked effect on enhancing muscle stamina and at longer times in
      limiting weight gain. In the established KK.Cg-Ay/J model of non-insulin
      dependent diabetes, oral administration of meglumine significantly improved
      glycemic control and significantly lowered levels of plasma and liver
      triglycerides. Compared to untreated control animals, meglumine reduced apparent
      diabetic nephropathy. Sorbitol can improve blood glucose uptake by liver and
      muscle in a manner associated with upregulation of the AMPK-related enzyme SNARK,
      but with undesirable gastrointestinal side effects not seen with meglumine. In
      murine myoblasts, we found that meglumine increased steady-state SNARK levels in
      a dose-dependent manner more potently than sorbitol. Taken together, these
      findings provide support for the clinical evaluation of meglumine as a low-cost,
      safe supplement offering the potential to improve muscle function, limit
      metabolic syndrome and reduce diabetic complications. 

PMID- 24587201
TI  - Infectious diseases and their outbreaks in Asia-Pacific: biodiversity and its
      regulation loss matter.
AB  - Despite increasing control measures, numerous parasitic and infectious diseases
      are emerging, re-emerging or causing recurrent outbreaks particularly in Asia and
      the Pacific region, a hot spot of both infectious disease emergence and
      biodiversity at risk. We investigate how biodiversity affects the distribution of
      infectious diseases and their outbreaks in this region, taking into account socio
      economics (population size, GDP, public health expenditure), geography (latitude
      and nation size), climate (precipitation, temperature) and biodiversity (bird and
      mammal species richness, forest cover, mammal and bird species at threat). We
      show, among countries, that the overall richness of infectious diseases is
      positively correlated with the richness of birds and mammals, but the number of
      zoonotic disease outbreaks is positively correlated with the number of threatened
      mammal and bird species and the number of vector-borne disease outbreaks is
      negatively correlated with forest cover. These results suggest that, among
      countries, biodiversity is a source of pathogens, but also that the loss of
      biodiversity or its regulation, as measured by forest cover or threatened
      species, seems to be associated with an increase in zoonotic and vector-borne
      disease outbreaks. 

PMID- 24587202
TI  - Early stage biomineralization in the periostracum of the 'living fossil' bivalve
      Neotrigonia.
AB  - A detailed investigation of the shell formation of the palaeoheterodont 'living
      fossil' Neotrigonia concentrated on the timing and manufacture of the calcified
      'bosses' which stud the outside of all trigonioid bivalves (extant and fossil)
      has been conducted. Electron microscopy and optical microscopy revealed that
      Neotrigonia spp. have a spiral-shaped periostracal groove. The periostracum
      itself is secreted by the basal cell, as a thin dark pellicle, becoming
      progressively transformed into a thin dark layer by additions of secretions from
      the internal outer mantle fold. Later, intense secretion of the internal surface
      of the outer mantle fold forms a translucent layer, which becomes transformed by
      tanning into a dark layer. The initiation of calcified bosses occurred at a very
      early stage of periostracum formation, deep within the periostracal groove
      immediately below the initialmost dark layer. At this stage, they consist of a
      series of polycyclically twinned crystals. The bosses grow as the periostracum
      traverse through the periostracal groove, in coordination with the thickening of
      the dark periostracal layer and until, upon reaching the mantle edge, they
      impinge upon each other and become transformed into large prisms separated by
      dark periostracal walls. In conclusion, the initial bosses and the external part
      of the prismatic layer are fully intraperiostracal. With later growth, the prisms
      transform into fibrous aggregates, although the details of the process are
      unknown. This reinforces the relationships with other groups that have the
      ability to form intraperiostracal calcifications, for example the unionoids with
      which the trigonioids form the clade Paleoheterodonta. The presence of similar
      structures in anomalodesmatans and other euheterodonts raises the question of
      whether this indicates a relationship or represents a convergence. The
      identification of very early calcification within an organic sheet has
      interesting implications for our understanding of how shells may have evolved. 

PMID- 24587203
TI  - Using mitogenomic and nuclear ribosomal sequence data to investigate the
      phylogeny of the Xiphinema americanum species complex.
AB  - Nematodes within the Xiphinema americanum species complex are economically
      important because they vector nepoviruses which cause considerable damage to a
      variety of agricultural crops. The taxonomy of X. americanum species complex is
      controversial, with the number of putative species being the subject of debate.
      Accurate phylogenetic knowledge of this group is highly desirable as it may
      ultimately reveal genetic differences between species. For this study, nematodes
      belonging to the X. americanum species complex, including potentially mixed
      species populations, were collected from 12 geographically disparate locations
      across the U.S. from different crops and in varying association with nepoviruses.
      At least four individuals from each population were analyzed. A portion of the
      18S nuclear ribosomal DNA (rDNA) gene was sequenced for all individuals while the
      internal transcribed spacer region 1 (ITS1) of rDNA was cloned and 2 to 6 clones
      per individual were sequenced. Mitochondrial genomes for numerous individuals
      were sequenced in parallel using high-throughput DNA sequencing (HTS) technology.
      Phylogenetic analysis of the 18S rDNA revealed virtually identical sequences
      across all populations. Analysis of ITS1 rDNA sequences revealed several well
      supported clades, with some degree of congruence with geographic location and
      viral transmission, but also numerous presumably paralogous sequences that failed
      to form clades with other sequences from the same population. Analysis of
      mitochondrial DNA (mtDNA) indicated the presence of three distinct monophyletic
      clades of X. americanum species complex nematodes. Two clades contained nematodes
      found in association with nepovirus and the third contained divergent mtDNA
      sequences from three nematode populations from the western U.S. where nepovirus
      was absent. The inherent heterogeneity in ITS1 rDNA sequence data and lack of
      informative sites in 18S rDNA analysis suggests that mtDNA may be more useful in
      sorting out the taxonomic confusion of the X. americanum species complex. 

PMID- 24587204
TI  - Fast segmentation of stained nuclei in terabyte-scale, time resolved 3D
      microscopy image stacks.
AB  - Automated analysis of multi-dimensional microscopy images has become an integral
      part of modern research in life science. Most available algorithms that provide
      sufficient segmentation quality, however, are infeasible for a large amount of
      data due to their high complexity. In this contribution we present a fast
      parallelized segmentation method that is especially suited for the extraction of
      stained nuclei from microscopy images, e.g., of developing zebrafish embryos. The
      idea is to transform the input image based on gradient and normal directions in
      the proximity of detected seed points such that it can be handled by
      straightforward global thresholding like Otsu's method. We evaluate the quality
      of the obtained segmentation results on a set of real and simulated benchmark
      images in 2D and 3D and show the algorithm's superior performance compared to
      other state-of-the-art algorithms. We achieve an up to ten-fold decrease in
      processing times, allowing us to process large data sets while still providing
      reasonable segmentation results. 

PMID- 24587205
TI  - Effect of lung volume on airway luminal area assessed by computed tomography in
      chronic obstructive pulmonary disease.
AB  - BACKGROUND: Although airway luminal area (Ai) is affected by lung volume (LV),
      how is not precisely understood. We hypothesized that the effect of LV on Ai
      would differ by airway generation, lung lobe, and chronic obstructive pulmonary
      disease (COPD) severity. METHODS: Sixty-seven subjects (15 at risk, 18, 20, and
      14 for COPD stages 1, 2, and 3) underwent pulmonary function tests and computed
      tomography scans at full inspiration and expiration (at functional residual
      capacity). LV and eight selected identical airways were measured in the right
      lung. Ai was measured at the mid-portion of the 3(rd), the segmental bronchus, to
      6(th) generation of the airways, leading to 32 measurements per subject. RESULTS:
      The ratio of expiratory to inspiratory LV (LV E/I ratio) and Ai (Ai E/I ratio)
      was defined for evaluation of changes. The LV E/I ratio increased as COPD
      severity progressed. As the LV E/I ratio was smaller, the Ai E/I ratio was
      smaller at any generation among the subjects. Overall, the Ai E/I ratios were
      significantly smaller at the 5(th) (61.5%) and 6(th) generations (63.4%) and than
      at the 3(rd) generation (73.6%, p<0.001 for each), and also significantly lower
      in the lower lobe than in the upper or middle lobe (p<0.001 for each). And, the
      Ai E/I ratio decreased as COPD severity progressed only when the ratio was
      corrected by the LV E/I ratio (at risk v.s. stage 3 p<0.001, stage 1 v.s. stage 3
      p<0.05). CONCLUSIONS: From full inspiration to expiration, the airway luminal
      area shrinks more at the distal airways compared with the proximal airways and in
      the lower lobe compared with the other lobes. Generally, the airways shrink more
      as COPD severity progresses, but this phenomenon becomes apparent only when lung
      volume change from inspiration to expiration is taken into account.

PMID- 24587206
TI  - Escherichia coli and Candida albicans induced macrophage extracellular trap-like
      structures with limited microbicidal activity.
AB  - The formation of extracellular traps (ETs) has recently been recognized as a
      novel defense mechanism in several types of innate immune cells. It has been
      suggested that these structures are toxic to microbes and contribute
      significantly to killing several pathogens. However, the role of ETs formed by
      macrophages (METs) in defense against microbes remains little known. In this
      study, we demonstrated that a subset of murine J774A.1 macrophage cell line (8%
      to 17%) and peritoneal macrophages (8.5% to 15%) form METs-like structures (METs
      LS) in response to Escherichia coli and Candida albicans challenge. We found only
      a portion of murine METs-LS, which are released by dying macrophages, showed
      detectable killing effects on trapped E. coli but not C. albicans. Fluorescence
      and scanning electron microscopy analyses revealed that, in vitro, both
      microorganisms were entrapped in J774A.1 METs-LS composed of DNA and microbicidal
      proteins such as histone, myeloperoxidase and lysozyme. DNA components of both
      nucleus and mitochondrion origins were detectable in these structures.
      Additionally, METs-LS formation occurred independently of ROS produced by NADPH
      oxidase, and this process did not result in cell lysis. In summary, our results
      emphasized that microbes induced METs-LS in murine macrophage cells and that the
      microbicidal activity of these METs-LS differs greatly. We propose the function
      of METs-LS is to contain invading microbes at the infection site, thereby
      preventing the systemic diffusion of them, rather than significantly killing
      them. 

PMID- 24587207
TI  - Regenerating 1 and 3b gene expression in the pancreas of type 2 diabetic Goto
      Kakizaki (GK) rats.
AB  - Regenerating (REG) proteins are associated with islet development, beta-cell
      damage, diabetes and pancreatitis. Particularly, REG-1 and REG-3-beta are
      involved in cell growth/survival and/or inflammation and the Reg1 promoter
      contains interleukin-6 (IL-6)-responsive elements. We showed by transcriptome
      analysis that islets of Goto-Kakizaki (GK) rats, a model of spontaneous type 2
      diabetes, overexpress Reg1, 3alpha, 3beta and 3gamma, vs Wistar islets. Goto
      Kakizaki rat islets also exhibit increased cytokine/chemokine expression/release,
      particularly IL-6. Here we analyzed Reg1 and Reg3beta expression and REG-1 immuno
      localization in the GK rat pancreas in relationship with inflammation. Isolated
      pancreatic islets and acinar tissue from male adult Wistar and diabetic GK rats
      were used for quantitative RT-PCR analysis. REG-1 immunohistochemistry was
      performed on paraffin sections with a monoclonal anti-rat REG-1 antibody. Islet
      cytokine/chemokine release was measured after 48 h-culture. Islet macrophage
      positive area was quantified on cryostat sections using anti-CD68 and major
      histocompatibility complex (MHC) class II antibodies. Pancreatic exocrine-to
      endocrine Reg1 and Reg3beta mRNA ratios were markedly increased in Wistar vs GK
      rats. Conversely, both genes were upregulated in isolated GK rat islets. These
      findings were unexpected, because Reg genes are expressed in the pancreatic
      acinar tissue. However, we observed REG-1 protein labeling in acinar peri-ductal
      tissue close to islets and around large, often disorganized, GK rat islets, which
      may retain acinar cells due to their irregular shape. These large islets also
      showed peri-islet macrophage infiltration and increased release of various
      cytokines/chemokines, particularly IL-6. Thus, IL-6 might potentially trigger
      acinar REG-1 expression and secretion in the vicinity of large diabetic GK rat
      islets. This increased acinar REG-1 expression might reflect an adaptive though
      unsuccessful response to deleterious microenvironment. 

PMID- 24587208
TI  - The complex genetic context of blaPER-1 flanked by miniature inverted-repeat
      transposable elements in Acinetobacter johnsonii.
AB  - On a large plasmid of Acinetobacter johnsonii strain XBB1 from hospital sewage,
      blaPER-1 and ISCR1 were found in a complex Tn402-like integron carrying an arr3
      aacA4 cassette array. The integron was truncated by the same 439-bp miniature
      inverted-repeat transposable element (MITE) at both ends. blaPER-1 and its
      complex surroundings might have been mobilized by the MITEst into an orf of
      unknown function, evidenced by the presence of the characteristic 5-bp direct
      target repeats. The same 439-bp MITEs have also been found flanking class 1
      integrons carrying metallo-beta-lactamases genes bla IMP-1, bla IMP-5 and bla VIM
      2 before but without ISCR1. Although the cassette arrays are different, integrons
      have always been truncated by the 439-bp MITEs at the exact same locations. The
      results suggested that MITEs might be able to mobilize class 1 integrons via
      transposition or homologous recombination and therefore represent a possible
      common mechanism for mobilizing antimicrobial resistance determinants.

PMID- 24587209
TI  - Therapeutic benefit of bone marrow-derived endothelial progenitor cell
      transplantation after experimental aneurysm embolization with coil in rats.
AB  - Aneurysm embolization with coil is now widely used clinically. However, the
      recurrence of aneurysms after embolization has always plagued neurosurgeons
      because the endothelial layer of the aneurysm neck loses its integrity after
      being embolized by coil. Bone marrow-derived endothelial progenitor cells (BM
      EPCs) could be incorporated into injured endothelium and differentiate into
      mature endothelial cells during vascular repairing processes. The aim of our
      study is to explore the effects of BM-EPCs on aneurysm repairing and remodeling
      in a rat embolization model of abdominal aortic aneurysm. BM-EPC proliferation,
      migration and tube formation were not affected by super-paramagnetic iron oxide
      nanoparticle (SPIO) labeling compared to the controls (p>0.05). The number of
      SPIO-labeled cells greatly increased in EPC transplanted rats compared to that of
      phosphate buffered saline treated rats. SPIO-labeled EPC (SPIO-EPC) are mainly
      located in the aneurysm neck and surrounded by fibrous tissue. A histology study
      showed that the aneurysm orifice was closed with neointima and the aneurysm was
      filled with newly formed fibrous tissue. The SPIO-EPC accumulated in the aneurysm
      neck, which accelerated focal fibrous tissue remodeling, suggesting that BM-EPCs
      play a crucial role in repairing and remodeling the aneurysm neck orifice. 

PMID- 24587211
TI  - Habitat-mediated variation in the importance of ecosystem engineers for secondary
      cavity nesters in a nest web.
AB  - Through physical state changes in biotic or abiotic materials, ecosystem
      engineers modulate resource availability to other organisms and are major drivers
      of evolutionary and ecological dynamics. Understanding whether and how ecosystem
      engineers are interchangeable for resource users in different habitats is a
      largely neglected topic in ecosystem engineering research that can improve our
      understanding of the structure of communities. We addressed this issue in a
      cavity-nest web (1999-2011). In aspen groves, the presence of mountain bluebird
      (Sialia currucoides) and tree swallow (Tachycineta bicolour) nests was positively
      related to the density of cavities supplied by northern flickers (Colaptes
      auratus), which provided the most abundant cavities (1.61 cavities/ha). Flickers
      in aspen groves provided numerous nesting cavities to bluebirds (66%) and
      swallows (46%), despite previous research showing that flicker cavities are
      avoided by swallows. In continuous mixed forests, however, the presence of
      nesting swallows was mainly related to cavity density of red-naped sapsuckers
      (Sphyrapicus nuchalis), which provided the most abundant cavities (0.52
      cavities/ha), and to cavity density of hairy woodpeckers (Picoides villosus),
      which provided few (0.14 cavities/ha) but high-quality cavities. Overall,
      sapsuckers and hairy woodpeckers provided 86% of nesting cavities to swallows in
      continuous forests. In contrast, the presence of nesting bluebirds in continuous
      forests was associated with the density of cavities supplied by all the ecosystem
      engineers. These results suggest that (i) habitat type may mediate the
      associations between ecosystem engineers and resource users, and (ii) different
      ecosystem engineers may be interchangeable for resource users depending on the
      quantity and quality of resources that each engineer supplies in each habitat
      type. We, therefore, urge the incorporation of the variation in the quantity and
      quality of resources provided by ecosystem engineers across habitats into models
      that assess community dynamics to improve our understanding of the importance of
      ecosystem engineers in shaping ecological communities. 

PMID- 24587210
TI  - Neuroprotective copper bis(thiosemicarbazonato) complexes promote neurite
      elongation.
AB  - Abnormal biometal homeostasis is a central feature of many neurodegenerative
      disorders including Alzheimer's disease (AD), Parkinson's disease (PD), and motor
      neuron disease. Recent studies have shown that metal complexing compounds
      behaving as ionophores such as clioquinol and PBT2 have robust therapeutic
      activity in animal models of neurodegenerative disease; however, the mechanism of
      neuroprotective action remains unclear. These neuroprotective or neurogenerative
      processes may be related to the delivery or redistribution of biometals, such as
      copper and zinc, by metal ionophores. To investigate this further, we examined
      the effect of the bis(thiosemicarbazonato)-copper complex, Cu(II)(gtsm) on
      neuritogenesis and neurite elongation (neurogenerative outcomes) in PC12 neuronal
      related cultures. We found that Cu(II)(gtsm) induced robust neurite elongation in
      PC12 cells when delivered at concentrations of 25 or 50 nM overnight. Analogous
      effects were observed with an alternative copper bis(thiosemicarbazonato)
      complex, Cu(II)(atsm), but at a higher concentration. Induction of neurite
      elongation by Cu(II)(gtsm) was restricted to neurites within the length range of
      75-99 um with a 2.3-fold increase in numbers of neurites in this length range
      with 50 nM Cu(II)(gtsm) treatment. The mechanism of neurogenerative action was
      investigated and revealed that Cu(II)(gtsm) inhibited cellular phosphatase
      activity. Treatment of cultures with 5 nM FK506 (calcineurin phosphatase
      inhibitor) resulted in analogous elongation of neurites compared to 50 nM
      Cu(II)(gtsm), suggesting a potential link between Cu(II)(gtsm)-mediated
      phosphatase inhibition and neurogenerative outcomes.

PMID- 24587212
TI  - Study of the plant COPII vesicle coat subunits by functional complementation of
      yeast Saccharomyces cerevisiae mutants.
AB  - The formation and budding of endoplasmic reticulum ER-derived vesicles depends on
      the COPII coat protein complex that was first identified in yeast Saccharomyces
      cerevisiae. The ER-associated Sec12 and the Sar1 GTPase initiate the COPII coat
      formation by recruiting the Sec23-Sec24 heterodimer following the subsequent
      recruitment of the Sec13-Sec31 heterotetramer. In yeast, there is usually one
      gene encoding each COPII protein and these proteins are essential for yeast
      viability, whereas the plant genome encodes multiple isoforms of all COPII
      subunits. Here, we used a systematic yeast complementation assay to assess the
      functionality of Arabidopsis thaliana COPII proteins. In this study, the
      different plant COPII subunits were expressed in their corresponding temperature
      sensitive yeast mutant strain to complement their thermosensitivity and secretion
      phenotypes. Secretion was assessed using two different yeast cargos: the soluble
      alpha-factor pheromone and the membranous v-SNARE (vesicle-soluble NSF (N
      ethylmaleimide-sensitive factor) attachment protein receptor) Snc1 involved in
      the fusion of the secretory vesicles with the plasma membrane. This
      complementation study allowed the identification of functional A. thaliana COPII
      proteins for the Sec12, Sar1, Sec24 and Sec13 subunits that could represent an
      active COPII complex in plant cells. Moreover, we found that AtSec12 and AtSec23
      were co-immunoprecipitated with AtSar1 in total cell extract of 15 day-old
      seedlings of A. thaliana. This demonstrates that AtSar1, AtSec12 and AtSec23 can
      form a protein complex that might represent an active COPII complex in plant
      cells. 

PMID- 24587213
TI  - Mutations of the Drosophila myosin regulatory light chain affect courtship song
      and reduce reproductive success.
AB  - The Drosophila indirect flight muscles (IFM) rely on an enhanced stretch
      activation response to generate high power output for flight. The IFM is neurally
      activated during the male courtship song, but its role, if any, in generating the
      small amplitude wing vibrations that produce the song is not known. Here, we
      examined the courtship song properties and mating behavior of three mutant
      strains of the myosin regulatory light chain (DMLC2) that are known to affect IFM
      contractile properties and impair flight: (i) Dmlc2(Delta2-46) (Ext), an N
      terminal extension truncation; (ii) Dmlc2(S66A,S67A) (Phos), a disruption of two
      MLC kinase phosphorylation sites; and (iii) Dmlc2(Delta2-46;S66A,S67A) (Dual),
      expressing both mutations. Our results show that the Dmlc2 gene is pleiotropic
      and that mutations that have a profound effect on flight mechanics (Phos and
      Dual) have minimal effects on courtship song. None of the mutations affect
      interpulse interval (IPI), a determinant of species-specific song, and intrapulse
      frequency (IPF) compared to Control (Dmlc2 (+) rescued null strain). However,
      abnormalities in the sine song (increased frequency) and the pulse song
      (increased cycles per pulse and pulse length) evident in Ext males are not
      apparent in Dual males suggesting that Ext and Phos interact differently in song
      and flight mechanics, given their known additive effect on the latter. All three
      mutant males produce a less vigorous pulse song and exhibit impaired mating
      behavior compared to Control males. As a result, females are less receptive to
      Ext, Phos, and Dual males when a Control male is present. These results open the
      possibility that DMLC2, and perhaps contractile protein genes in general, are
      partly under sexual selection. That mutations in DMLC2 manifest differently in
      song and flight suggest that this protein fulfills different roles in song and
      flight and that stretch activation plays a smaller role in song production than
      in flight. 

PMID- 24587214
TI  - The Association between walking and perceived environment in Chinese community
      residents: a cross-sectional study.
AB  - BACKGROUND: The neighborhood environment, as a determinant of walking, has been
      assessed in several developed countries. However, few studies have investigated
      these associations in Chinese populations. OBJECTIVE: To examine the association
      between the perceived neighborhood environment and walking for recreation or
      transportation purposes among Chinese community residents. METHODS: We used a
      multi-stage stratified random sampling design to conduct a cross-sectional study
      of 1528 Chinese adults in Shanghai. Environmental and walking variables were
      assessed using a revised Abbreviated Neighborhood Environment Walkability Scale
      for Chinese subjects and a long version of International Physical Activity
      Questionnaire. Self-reported demographic variables including gender, age,
      employment status, and location of community were also collected. Multiple
      logistic regression analysis was applied to examine the association between the
      neighborhood environment and walking. RESULTS: Based on the results of IPAQ,
      13.7% of the overall subjects were physical inactive, which was considered to be
      lowly active. For all participants, accessibility to services was significantly
      associated with walking for both recreation and transportation (odds ratio=1.062,
      95% confidence interval: 1.016, 1.110; odds ratio=1.053; 95% confidence interval:
      1.008, 1.100, respectively). In males, accessibility to services was
      significantly associated both with walking for recreation and walking for
      transportation. However, a significantly negative association was found between
      the neighborhood surroundings and walking for recreation. In contrast, females
      who perceived good traffic safety tended to walk for recreation. Data also
      revealed a difference between working and retired individuals. Among working
      participants, perceived environmental variables were not significantly associated
      with walking for recreation and transportation. CONCLUSIONS: The association
      between neighborhood environment and walking varied depending on the reason for
      walking and the characteristics of the participants. Our findings suggest that
      interventions to promote walking in community residents should include improving
      the neighborhood environment, particularly accessibility to services such as
      building more stores, parks, and public transit facilities.

PMID- 24587215
TI  - Pollination and plant resources change the nutritional quality of almonds for
      human health.
AB  - Insect-pollinated crops provide important nutrients for human health.
      Pollination, water and nutrients available to crops can influence yield, but it
      is not known if the nutritional value of the crop is also influenced. Almonds are
      an important source of critical nutrients for human health such as unsaturated
      fat and vitamin E. We manipulated the pollination of almond trees and the
      resources available to the trees, to investigate the impact on the nutritional
      composition of the crop. The pollination treatments were: (a) exclusion of
      pollinators to initiate self-pollination and (b) hand cross-pollination; the
      plant resource treatments were: (c) reduced water and (d) no fertilizer. In an
      orchard in northern California, trees were exposed to a single treatment or a
      combination of two (one pollination and one resource). Both the fat and vitamin E
      composition of the nuts were highly influenced by pollination. Lower proportions
      of oleic to linoleic acid, which are less desirable from both a health and
      commercial perspective, were produced by the self-pollinated trees. However,
      higher levels of vitamin E were found in the self-pollinated nuts. In some cases,
      combined changes in pollination and plant resources sharpened the pollination
      effects, even when plant resources were not influencing the nutrients as an
      individual treatment. This study highlights the importance of insects as
      providers of cross-pollination for fruit quality that can affect human health,
      and, for the first time, shows that other environmental factors can sharpen the
      effect of pollination. This contributes to an emerging field of research
      investigating the complexity of interactions of ecosystem services affecting the
      nutritional value and commercial quality of crops. 

PMID- 24587216
TI  - Diminution of hepatic response to 7, 12-dimethylbenz(alpha)anthracene by ethyl
      acetate fraction of Acacia catechu willd. through modulation of xenobiotic and
      anti-oxidative enzymes in rats.
AB  - BACKGROUND: Liver is the primary metabolizing site of body and is prone to damage
      by exogenous as well as endogenous intoxicants. Polycyclic aromatic hydrocarbons
      such as 7, 12- dimethylbenz(alpha)anthracene (DMBA) is an exogenous hepatotoxin,
      which is well known for modulating phase I, II and anti-oxidative enzymes of
      liver. Plants contain plethora of polyphenolic compounds which can reverse the
      damaging effect of various xenobiotics. The present study investigated protective
      role of the ethyl acetate fraction of Acacia catechu Willd. (EAF) against DMBA
      induced alteration in hepatic metabolizing and anti-oxidative enzymes in rats.
      METHODOLOGY AND PRINCIPAL FINDINGS: The rats were subjected to hepatic damage by
      treating with DMBA for 7 weeks on alternative days and treatment schedule was
      terminated at the end of 14 weeks. The rats were euthanized at the end of
      protocol and livers were homogenized. The liver homogenates were used to analyse
      phase I (NADPH-cytochrome P450 reducatse, NADH-cytochrome b5 reductase,
      cytochrome P420, cytochrome b5), phase II (glutathione-S-transferase, DT
      diaphorase and gamma-Glutamyl transpeptidase) and antioxidative enzymes
      (catalase, superoxide dismutase, ascorbate peroxidase, glutathione reductase,
      guiacol peroxidase and lactate dehydrogenase). Furthermore, other oxidative
      stress parameters (thiobarbituric acid reactive substances, lipid hydroperoxides
      and conjugated dienes and reduced glutathione) and liver marker enzymes (serum
      glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase and
      alkaline phosphatase) were also studied. The DMBA induced significant changes in
      activity of hepatic enzymes that was reversed by treatment with three dose levels
      of EAF. CONCLUSION: It is concluded that EAF affords hepato-protection against
      DMBA in rats through modulation of phase I, II and anti-oxidative enzymes.

PMID- 24587217
TI  - Factors influencing germination of a functionally important grassland plant, Iris
      tenax.
AB  - Grassland prairies of western Oregon and Washington are among the most endangered
      ecosystems in the United States. Active management and restoration are needed to
      promote biodiversity in the region. To support plant production for use in
      habitat restoration, we developed germination protocols for greenhouse
      propagation of Iris tenax (Oregon iris). Dormancy was most effectively overcome
      (63% germination) by four weeks of warm stratification at 20/30 degrees C
      followed by 6-12 weeks of cold stratification at 5 degrees C suggesting that I.
      tenax may have morphophysiological dormancy. This result was consistent across
      multiple source populations. 

PMID- 24587218
TI  - NAC, tiron and trolox impair survival of cell cultures containing glioblastoma
      tumorigenic initiating cells by inhibition of cell cycle progression.
AB  - Reactive oxygen species (ROS) are metabolism by-products that may act as
      signaling molecules to sustain tumor growth. Antioxidants have been used to
      impair cancer cell survival. Our goal was to determine the mechanisms involved in
      the response to antioxidants of a human cell culture (PT4) containing
      glioblastoma (GBM) tumorigenic initiating cells (TICs). ROS production in the
      absence or presence of N-acetyl-L-cysteine (NAC), tiron, and trolox was evaluated
      by flow cytometry (FCM). The effects of these antioxidants on cell survival and
      apoptosis were evaluated by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
      bromide assay (MTT) and FCM. The biological processes modulated by these drugs
      were determined by oligonucleotide microarray gene expression profiling. Our
      results showed that NAC, tiron and trolox impaired PT4 cell survival, had minor
      effects on ROS levels and caused wide deregulation of cell cycle genes.
      Furthermore, tiron and trolox caused inhibition of cell survival in two
      additional cell cultures containing TICs, FO-1 and MM1, established from a
      melanoma and a mesothelioma patient, respectively. NAC, instead, impaired
      survival of the MM1 cells but not of the FO-1 cells. However, when used in
      combination, NAC enhanced the inhibitory effect of PLX4032 (BRAF V600E inhibitor)
      and Gefitinib (EGFR inhibitor), on FO-1 and PT4 cell survival. Collectively, NAC,
      tiron and trolox modulated gene expression and impaired the growth of cultures
      containing TICs primarily by inhibiting cell cycle progression. 

PMID- 24587219
TI  - Genetic structure and diversity of the endangered fir tree of Lebanon (Abies
      cilicica Carr.): implications for conservation.
AB  - The threatened conifer Abies cilicica currently persists in Lebanon in
      geographically isolated forest patches. The impact of demographic and
      evolutionary processes on population genetic diversity and structure were
      assessed using 10 nuclear microsatellite loci. All remnant 15 local populations
      revealed a low genetic variation but a high recent effective population size. FST
      -based measures of population genetic differentiation revealed a low spatial
      genetic structure, but Bayesian analysis of population structure identified a
      significant Northeast-Southwest population structure. Populations showed
      significant but weak isolation-by-distance, indicating non-equilibrium conditions
      between dispersal and genetic drift. Bayesian assignment tests detected an
      asymmetric Northeast-Southwest migration involving some long-distance dispersal
      events. We suggest that the persistence and Northeast-Southwest geographic
      structure of Abies cilicica in Lebanon is the result of at least two demographic
      processes during its recent evolutionary history: (1) recent migration to
      currently marginal populations and (2) local persistence through altitudinal
      shifts along a mountainous topography. These results might help us better
      understand the mechanisms involved in the species response to expected climate
      change. 

PMID- 24587220
TI  - New hydrocarbon degradation pathways in the microbial metagenome from Brazilian
      petroleum reservoirs.
AB  - Current knowledge of the microbial diversity and metabolic pathways involved in
      hydrocarbon degradation in petroleum reservoirs is still limited, mostly due to
      the difficulty in recovering the complex community from such an extreme
      environment. Metagenomics is a valuable tool to investigate the genetic and
      functional diversity of previously uncultured microorganisms in natural
      environments. Using a function-driven metagenomic approach, we investigated the
      metabolic abilities of microbial communities in oil reservoirs. Here, we describe
      novel functional metabolic pathways involved in the biodegradation of aromatic
      compounds in a metagenomic library obtained from an oil reservoir. Although many
      of the deduced proteins shared homology with known enzymes of different well
      described aerobic and anaerobic catabolic pathways, the metagenomic fragments did
      not contain the complete clusters known to be involved in hydrocarbon
      degradation. Instead, the metagenomic fragments comprised genes belonging to
      different pathways, showing novel gene arrangements. These results reinforce the
      potential of the metagenomic approach for the identification and elucidation of
      new genes and pathways in poorly studied environments and contribute to a broader
      perspective on the hydrocarbon degradation processes in petroleum reservoirs. 

PMID- 24587221
TI  - Chronic exposure to GLP-1 increases GLP-1 synthesis and release in a pancreatic
      alpha cell line (alpha-TC1): evidence of a direct effect of GLP-1 on pancreatic
      alpha cells.
AB  - AIMS/HYPOTHESIS: Incretin therapies, which are used to treat diabetic patients,
      cause a chronic supra-physiological increase in GLP-1 circulating levels. It is
      still unclear how the resulting high hormone concentrations may affect pancreatic
      alpha cells. The present study was designed to investigate the effects of chronic
      exposure to high GLP-1 levels on a cultured pancreatic alpha cell line. METHODS:
      alpha-TC1-6 cell line was cultured in the presence or absence of GLP-1 (100
      nmol/l) for up to 72 h. In our model GLP-1 receptor (GLP-1R) was measured. After
      the cells were exposed to GLP-1 the levels of glucagon secretion were measured.
      Because GLP-1 acts on intracellular cAMP production, the function of GLP-1R was
      studied. We also investigated the effects of chronic GLP-1 exposure on the
      cAMP/MAPK pathway, Pax6 levels, the expression of prohormone convertases (PCs),
      glucagon gene (Gcg) and protein expression, glucagon and GLP-1 production.
      RESULTS: In our model, we were able to detect GLP-1R. After GLP-1 exposure we
      found a reduction in glucagon secretion. During further investigation of the
      function of GLP-1R, we found an activation of the cAMP/MAPK/Pax6 pathway and an
      increase of Gcg gene and protein expression. Furthermore we observed a
      significant increase in PC1/3 protein expression, GLP-1 intracellular content and
      GLP-1 secretion. CONCLUSIONS/INTERPRETATION: Our data indicate that the chronic
      exposure of pancreatic alpha cells to GLP-1 increases the ability of these cells
      to produce and release GLP-1. This phenomenon occurs through the stimulation of
      the transcription factor Pax6 and the increased expression of the protein
      convertase PC1/3.

PMID- 24587222
TI  - Using mathematical transmission modelling to investigate drivers of respiratory
      syncytial virus seasonality in children in the Philippines.
AB  - We used a mathematical transmission model to estimate when ecological drivers of
      respiratory syncytial virus (RSV) transmissibility would need to act in order to
      produce the observed seasonality of RSV in the Philippines. We estimated that a
      seasonal peak in transmissibility would need to occur approximately 51 days prior
      to the observed peak in RSV cases (range 49 to 67 days). We then compared this
      estimated seasonal pattern of transmissibility to the seasonal patterns of
      possible ecological drivers of transmissibility: rainfall, humidity and
      temperature patterns, nutritional status, and school holidays. The timing of the
      seasonal patterns of nutritional status and rainfall were both consistent with
      the estimated seasonal pattern of transmissibility and these are both plausible
      drivers of the seasonality of RSV in this setting. 

PMID- 24587223
TI  - De novo peptide design and experimental validation of histone methyltransferase
      inhibitors.
AB  - Histones are small proteins critical to the efficient packaging of DNA in the
      nucleus. DNA-protein complexes, known as nucleosomes, are formed when the DNA
      winds itself around the surface of the histones. The methylation of histone
      residues by enhancer of zeste homolog 2 (EZH2) maintains gene repression over
      successive cell generations. Overexpression of EZH2 can silence important tumor
      suppressor genes leading to increased invasiveness of many types of cancers. This
      makes the inhibition of EZH2 an important target in the development of cancer
      therapeutics. We employed a three-stage computational de novo peptide design
      method to design inhibitory peptides of EZH2. The method consists of a sequence
      selection stage and two validation stages for fold specificity and approximate
      binding affinity. The sequence selection stage consists of an integer linear
      optimization model that was solved to produce a rank-ordered list of amino acid
      sequences with increased stability in the bound peptide-EZH2 structure. These
      sequences were validated through the calculation of the fold specificity and
      approximate binding affinity of the designed peptides. Here we report the
      discovery of novel EZH2 inhibitory peptides using the de novo peptide design
      method. The computationally discovered peptides were experimentally validated in
      vitro using dose titrations and mechanism of action enzymatic assays. The peptide
      with the highest in vitro response, SQ037, was validated in nucleo using
      quantitative mass spectrometry-based proteomics. This peptide had an IC50 of 13.5
      [Formula: see text]M, demonstrated greater potency as an inhibitor when compared
      to the native and K27A mutant control peptides, and demonstrated competitive
      inhibition versus the peptide substrate. Additionally, this peptide demonstrated
      high specificity to the EZH2 target in comparison to other histone
      methyltransferases. The validated peptides are the first computationally designed
      peptides that directly inhibit EZH2. These inhibitors should prove useful for
      further chromatin biology investigations. 

PMID- 24587224
TI  - The effect of paternal age on offspring intelligence and personality when
      controlling for paternal trait level.
AB  - Paternal age at conception has been found to predict the number of new genetic
      mutations. We examined the effect of father's age at birth on offspring
      intelligence, head circumference and personality traits. Using the Minnesota Twin
      Family Study sample we tested paternal age effects while controlling for parents'
      trait levels measured with the same precision as offspring's. From evolutionary
      genetic considerations we predicted a negative effect of paternal age on
      offspring intelligence, but not on other traits. Controlling for parental
      intelligence (IQ) had the effect of turning an initially positive association non
      significantly negative. We found paternal age effects on offspring IQ and
      Multidimensional Personality Questionnaire Absorption, but they were not robustly
      significant, nor replicable with additional covariates. No other noteworthy
      effects were found. Parents' intelligence and personality correlated with their
      ages at twin birth, which may have obscured a small negative effect of advanced
      paternal age (<1% of variance explained) on intelligence. We discuss future
      avenues for studies of paternal age effects and suggest that stronger research
      designs are needed to rule out confounding factors involving birth order and the
      Flynn effect. 

PMID- 24587225
TI  - HIV-1 adenoviral vector vaccines expressing multi-trimeric BAFF and 4-1BBL
      enhance T cell mediated anti-viral immunity.
AB  - Adenoviral vectored vaccines have shown considerable promise but could be
      improved by molecular adjuvants. Ligands in the TNF superfamily (TNFSF) are
      potential adjuvants for adenoviral vector (Ad5) vaccines based on their central
      role in adaptive immunity. Many TNFSF ligands require aggregation beyond the
      trimeric state (multi-trimerization) for optimal biological function. Here we
      describe Ad5 vaccines for HIV-1 Gag antigen (Ad5-Gag) adjuvanted with the TNFSF
      ligands 4-1BBL, BAFF, GITRL and CD27L constructed as soluble multi-trimeric
      proteins via fusion to Surfactant Protein D (SP-D) as a multimerization scaffold.
      Mice were vaccinated with Ad5-Gag combined with Ad5 expressing one of the SP-D
      TNFSF constructs or single-chain IL-12p70 as adjuvant. To evaluate vaccine
      induced protection, mice were challenged with vaccinia virus expressing Gag
      (vaccinia-Gag) which is known to target the female genital tract, a major route
      of sexually acquired HIV-1 infection. In this system, SP-D-4-1BBL or SP-D-BAFF
      led to significantly reduced vaccinia-Gag replication when compared to Ad5-Gag
      alone. In contrast, IL-12p70, SP-D-CD27L and SP-D-GITRL were not protective.
      Histological examination following vaccinia-Gag challenge showed a dramatic
      lymphocytic infiltration into the uterus and ovaries of SP-D-4-1BBL and SP-D-BAFF
      treated animals. By day 5 post challenge, proinflammatory cytokines in the tissue
      were reduced, consistent with the enhanced control over viral replication.
      Splenocytes had no specific immune markers that correlated with protection
      induced by SP-D-4-1BBL and SP-D-BAFF versus other groups. IL-12p70, despite lack
      of anti-viral efficacy, increased the total numbers of splenic dextramer positive
      CD8+ T cells, effector memory T cells, and effector Gag-specific CD8+ T cells,
      suggesting that these markers are poor predictors of anti-viral immunity in this
      model. In conclusion, soluble multi-trimeric 4-1BBL and BAFF adjuvants led to
      strong protection from vaccinia-Gag challenge, but the protection was independent
      of standard immune markers. Soluble multi-trimeric SP-D-4-1BBL and SP-D-BAFF
      provide a novel technology to enhance adenoviral vector vaccines against HIV-1. 

PMID- 24587226
TI  - Relationship between serum ferritin levels and sarcopenia in Korean females aged
      60 years and older using the fourth Korea National Health and Nutrition
      Examination Survey (KNHANES IV-2, 3), 2008-2009.
AB  - CONTEXT: It has been suggested that elevated serum ferritin is associated with
      several metabolic disorders. However, there is no reported study assessing any
      association between serum ferritin and sarcopenia despite the close relationship
      between sarcopenia and metabolic disorders. OBJECTIVE: We investigated whether
      serum ferritin was associated with sarcopenia in older Koreans. DESIGN AND
      SETTING: We conducted a cross-sectional study based on data acquired in the
      second and third years (2008-9) of the fourth Korean National Health and
      Nutrition Examination Survey. PARTICIPANTS: In total, 952 men (mean age 69.0
      years) and 1,380 women (mean age 69.3 years) aged 60 years and older completed a
      body composition study using dual energy X-ray absorptiometry. MEASUREMENTS:
      Serum ferritin levels were measured. Sarcopenia was defined as an appendicular
      skeletal mass as a percentage of body weight that was less than two standard
      deviations below the gender-specific mean for young adults. RESULTS: Serum
      ferritin levels were lower in women than in men. Women with sarcopenia showed a
      higher level of serum ferritin than women without sarcopenia (men: without
      sarcopenia 115.7 ng/mL and with sarcopenia 134.4 ng/mL vs. women: without
      sarcopenia 70.7 ng/mL and with sarcopenia 85.4 ng/mL). The prevalence of
      sarcopenia increased as the tertile of serum ferritin increased. However,
      statistical significance was only seen in elderly women (1(st) tertile 6.3%,
      2(nd) tertile 8.0%, 3(rd) tertile 12.0%; p = 0.008). Without adjustment, compared
      with those in the lowest tertile of serum ferritin level, participants in the
      highest tertile had an odds ratio of 2.02 (95% confidence interval = 1.26-3.23)
      for sarcopenia in women. After adjusting for known risk factors, the OR for
      sarcopenia was 1.74 (95% CI = 1.02-2.97) in women. There was no statistically
      significant association between sarcopenia and serum ferritin tertiles in men.
      CONCLUSIONS: Elevated serum ferritin levels were associated with an increased
      prevalence of sarcopenia in women but not in men from a representative sample of
      elderly Koreans.

PMID- 24587227
TI  - Association between hypoxia and perinatal arterial ischemic stroke: a meta
      analysis.
AB  - BACKGROUND: Perinatal arterial ischemic stroke (AIS) occurs in an estimated 17 to
      93 per 100000 live births, yet the etiology is poorly understood. Although
      investigators have implicated hypoxia as a potential cause of AIS, the role of
      hypoxia in AIS remains controversial. The aim of this study was to estimate the
      association between perinatal hypoxia factors and perinatal arterial ischemic
      stroke through a meta-analysis of published observational studies. PATIENTS AND
      METHODS: A systematic search of electronically available studies published
      through July 2013 was conducted. Publication bias and heterogeneity across
      studies were evaluated and summary odds ratios (ORs) and 95% confidence intervals
      (CIs) were calculated with fixed-effects or random-effects models. RESULTS: A
      total of 8 studies describing the association between perinatal hypoxia factors
      and neonatal arterial ischemic stroke (AIS) met inclusion criteria, and 550
      newborns with AIS were enrolled. The associations were found for AIS:
      preeclampsia (OR 2.14; 95% CI, 1.25 to 3.66), ventouse delivery (OR 2.23; 95% CI,
      1.26 to 3.97), fetal heart rate abnormalities (OR 6.30; 95% CI, 3.84 to 10.34),
      reduced fetal movement (OR 5.35; 95% CI, 2.17 to 13.23), meconium-stained liquor
      (OR 3.05; 95% CI, 2.02 to 4.60), low Apgar score (OR 5.77; 95% CI, 1.66 to 20.04)
      and resuscitation at birth (OR 4.59; 95% CI, 3.23 to 6.52). Our data did not show
      any significant change of the mean risk estimate for oxytocin induction (OR 1.33;
      95% CI, 0.84 to 2.11) and low arterial umbilical cord ph (OR 4.63; 95% CI 2.14 to
      9.98). CONCLUSIONS: There is a significant association between perinatal hypoxia
      factors and AIS. The result indicates that perinatal hypoxia maybe one of causes
      of AIS. Large scale prospective clinical studies are still warranted.

PMID- 24587228
TI  - Targeted delivery of erythropoietin by transcranial focused ultrasound for
      neuroprotection against ischemia/reperfusion-induced neuronal injury: a long-term
      and short-term study.
AB  - Erythropoietin (EPO) is a neuroprotective agent against cerebral
      ischemia/reperfusion (I/R)-induced brain injury. However, its crossing of blood
      brain barrier is limited. Focused ultrasound (FUS) sonication with microbubbles
      (MBs) can effectively open blood-brain barrier to boost the vascular
      permeability. In this study, we investigated the effects of MBs/FUS on extending
      the therapeutic time window of EPO and its neuroprotective effects in both acute
      and chronic phases. Male Wistar rats were firstly subjected to two common carotid
      arteries and right middle cerebral artery occlusion (three vessels occlusion,
      3VO) for 50 min, and then the rats were treated with hEPO (human recombinant EPO,
      5000 IU/kg) with or without MBs/FUS at 5 h after occlusion/reperfusion. Acute
      phase investigation (I/R, I/R+MBs/FUS, I/R+hEPO, and I/R+hEPO+MBs/FUS) was
      performed 24 h after I/R; chronic tests including cylinder test and gait analysis
      were performed one month after I/R. The experimental results showed that MBs/FUS
      significantly increased the cerebral content of EPO by bettering vascular
      permeability. In acute phase, both significant improvement of neurological score
      and reduction of infarct volume were found in the I/R+hEPO+MBs/FUS group, as
      compared with I/R and I/R+hEPO groups. In chronic phase, long-term behavioral
      recovery and neuronal loss in brain cortex after I/R injury was significantly
      improved in the I/R+hEPO+MBs/FUS group. This study indicates that hEPO
      administration with MBs/FUS sonication even at 5 h after occlusion/reperfusion
      can produce a significant neuroprotection. 

PMID- 24587229
TI  - Population of computational rabbit-specific ventricular action potential models
      for investigating sources of variability in cellular repolarisation.
AB  - Variability is observed at all levels of cardiac electrophysiology. Yet, the
      underlying causes and importance of this variability are generally unknown, and
      difficult to investigate with current experimental techniques. The aim of the
      present study was to generate populations of computational ventricular action
      potential models that reproduce experimentally observed intercellular variability
      of repolarisation (represented by action potential duration) and to identify its
      potential causes. A systematic exploration of the effects of simultaneously
      varying the magnitude of six transmembrane current conductances (transient
      outward, rapid and slow delayed rectifier K(+), inward rectifying K(+), L-type
      Ca(2+), and Na(+)/K(+) pump currents) in two rabbit-specific ventricular action
      potential models (Shannon et al. and Mahajan et al.) at multiple cycle lengths
      (400, 600, 1,000 ms) was performed. This was accomplished with distributed
      computing software specialised for multi-dimensional parameter sweeps and grid
      execution. An initial population of 15,625 parameter sets was generated for both
      models at each cycle length. Action potential durations of these populations were
      compared to experimentally derived ranges for rabbit ventricular myocytes. 1,352
      parameter sets for the Shannon model and 779 parameter sets for the Mahajan model
      yielded action potential duration within the experimental range, demonstrating
      that a wide array of ionic conductance values can be used to simulate a
      physiological rabbit ventricular action potential. Furthermore, by using clutter
      based dimension reordering, a technique that allows visualisation of multi
      dimensional spaces in two dimensions, the interaction of current conductances and
      their relative importance to the ventricular action potential at different cycle
      lengths were revealed. Overall, this work represents an important step towards a
      better understanding of the role that variability in current conductances may
      play in experimentally observed intercellular variability of rabbit ventricular
      action potential repolarisation. 

PMID- 24587230
TI  - Microbial successions and metabolite changes during fermentation of salted shrimp
      (saeu-jeot) with different salt concentrations.
AB  - To investigate the effects of salt concentration on saeu-jeot (salted shrimp)
      fermentation, four sets of saeu-jeot samples with 20%, 24%, 28%, and 32% salt
      concentrations were prepared, and the pH, bacterial and archaeal abundances,
      bacterial communities, and metabolites were monitored during the entire
      fermentation period. Quantitative PCR showed that Bacteria were much more
      abundant than Archaea in all saeu-jeot samples, suggesting that bacterial
      populations play more important roles than archaeal populations even in highly
      salted samples. Community analysis indicated that Vibrio, Photobacterium,
      Psychrobacter, Pseudoalteromonas, and Enterovibrio were identified as the
      initially dominant genera, and the bacterial successions were significantly
      different depending on the salt concentration. During the early fermentation
      period, Salinivibrio predominated in the 20% salted samples, whereas
      Staphylococcus, Halomonas, and Salimicrobium predominated in the 24% salted
      samples; eventually, Halanaerobium predominated in the 20% and 24% salted
      samples. The initially dominant genera gradually decreased as the fermentation
      progressed in the 28% and 32% salted samples, and eventually Salimicrobium became
      predominant in the 28% salted samples. However, the initially dominant genera
      still remained until the end of fermentation in the 32% salted samples.
      Metabolite analysis showed that the amino acid profile and the initial glycerol
      increase were similar in all saeu-jeot samples regardless of the salt
      concentration. After 30-80 days of fermentation, the levels of acetate, butyrate,
      and methylamines in the 20% and 24% salted samples increased with the growth of
      Halanaerobium, even though the amino acid concentrations steadily increased until
      approximately 80-107 days of fermentation. This study suggests that a range of 24
      28% salt concentration in saeu-jeot fermentation is appropriate for the
      production of safe and tasty saeu-jeot. 

PMID- 24587231
TI  - Abrogation of TNFalpha production during cancer immunotherapy is crucial for
      suppressing side effects due to the systemic expression of IL-12.
AB  - For more than a decade, the cytokine interleukin-12 (IL-12) has been utilized,
      either alone or in combination with other drugs, as a treatment for cancer. The
      numerous anti-tumor properties of IL-12 still generate interest in the clinical
      use of this cytokine, even though it has demonstrated toxicity when administrated
      systemically. As an approach to overcome this toxicity, numerous laboratories
      have attempted to induce IL-12 expression at the site of the tumor. However for
      tumors that are difficult to remove surgically or for the treatment of
      disseminated metastases, systemic expression of this cytokine still remains as
      the most efficient method of administration. Nevertheless, finding alternative
      approaches for the use of IL-12 in the treatment of cancer and unraveling the
      basis of IL-12-side effects remain a challenge. In the present work we
      demonstrate that systemic expression of IL-12 through hydrodynamic injection of
      IL-12 cDNA is able to induce different types of liver lesions associated with a
      toxic pathology. However we report here that hepatic toxicity is diminished and
      survival of mice enhanced in the absence of tumor necrosis factor alpha
      (TNFalpha). This observation is in contrast to several murine models and clinical
      trials that postulate interferon gamma (IFNgamma) as the main cytokine
      responsible for IL-12 toxicity. Moreover, our work demonstrates that when IL-12
      cDNA is co-injected with IL-18 cDNA or when mice are pre-treated with a low dose
      of IL-12 cDNA prior to receiving a high dose of IL-12 cDNA, systemic levels of
      TNFalpha are almost completely abrogated, resulting in improved survival and less
      hepatic damage. Importantly, abrogation of TNFalpha signaling does not affect the
      strong anti-tumor activity of IL-12. Thus, neutralizing TNFalpha with antagonists
      already approved for human use offers a promising approach to abrogate IL-12 side
      effects during the use of this cytokine for the treatment of cancer.

PMID- 24587232
TI  - Antibody-mediated inhibition of TNFR1 attenuates disease in a mouse model of
      multiple sclerosis.
AB  - Tumour necrosis factor (TNF) is a proinflammatory cytokine that is known to
      regulate inflammation in a number of autoimmune diseases, including multiple
      sclerosis (MS). Although targeting of TNF in models of MS has been successful,
      the pathological role of TNF in MS remains unclear due to clinical trials where
      the non-selective inhibition of TNF resulted in exacerbated disease. Subsequent
      experiments have indicated that this may have resulted from the divergent effects
      of the two TNF receptors, TNFR1 and TNFR2. Here we show that the selective
      targeting of TNFR1 with an antagonistic antibody ameliorates symptoms of the most
      common animal model of MS, experimental autoimmune encephalomyelitis (EAE), when
      given following both a prophylactic and therapeutic treatment regime. Our results
      demonstrate that antagonistic TNFR1-specific antibodies may represent a
      therapeutic approach for the treatment of MS in the future. 

PMID- 24587233
TI  - Effectiveness of online self-help for suicidal thoughts: results of a randomised
      controlled trial.
AB  - BACKGROUND: Many people with suicidal thoughts do not receive treatment. The
      Internet can be used to reach more people in need of support. OBJECTIVE: To test
      the effectiveness of unguided online self-help to reduce suicidal thoughts.
      METHOD: 236 adults with mild to moderate suicidal thoughts were randomised to the
      intervention (n=116) or a waitlist control group (n=120). Assessments took place
      at baseline, and 2, 4 and 6 weeks later. Primary outcome was suicidal thoughts.
      Secondary outcomes were depressive symptoms, anxiety, hopelessness, worry, and
      health status. RESULTS: The intervention group showed a small significant effect
      in reducing suicidal thoughts (d=0.28). Effects were more pronounced for those
      with a history of repeated suicide attempts. There was also a significant
      reduction in worry (d=0.33). All other secondary outcomes showed small but non
      significant improvements. CONCLUSIONS: Although effect sizes were small, the
      reach of the internet could enable this intervention to help many people reduce
      their suicidal thoughts. TRIAL REGISTRATION: Netherlands Trial Register NTR1689.

PMID- 24587234
TI  - Niche overlap of congeneric invaders supports a single-species hypothesis and
      provides insight into future invasion risk: implications for global management of
      the Bactrocera dorsalis complex.
AB  - BACKGROUND: The invasive fruit fly, Bactrocera invadens, has expanded its range
      rapidly over the past 10 years. Here we aimed to determine if the recent range
      expansion of Bactrocera invadens into southern Africa can be better understood
      through niche exploration tools, ecological niche models (ENMs), and through
      incorporating information about Bactrocera dorsalis s.s., a putative conspecific
      species from Asia. We test for niche overlap of environmental variables between
      Bactrocera invadens and Bactrocera dorsalis s.s. as well as two other putative
      conspecific species, Bactrocera philippinensis and B. papayae. We examine overlap
      and similarity in the geographical expression of each species' realised niche
      through reciprocal distribution models between Africa and Asia. We explore
      different geographical backgrounds, environmental variables and model complexity
      with multiple and single Bactrocera species hypotheses in an attempt to predict
      the recent range expansion of B. invadens into northern parts of South Africa.
      PRINCIPAL FINDINGS: Bactrocera invadens has a high degree of niche overlap with
      B. dorsalis s.s. (and B. philippinensis and B. papayae). Ecological niche models
      built for Bactrocera dorsalis s.s. have high transferability to describe the
      range of B. invadens, and B. invadens is able to project to the core range of B.
      dorsalis s.s. The ENMs of both Bactrocera dorsalis and B. dorsalis combined with
      B. philipenesis and B. papayae have significantly higher predictive ability to
      capture the distribution points in South Africa than for B. invadens alone.
      CONCLUSIONS/SIGNIFICANCE: Consistent with other studies proposing these
      Bactrocera species as conspecific, niche similarity and overlap between these
      species is high. Considering these other Bactrocera dorsalis complex species
      simultaneously better describes the range expansion and invasion potential of B.
      invadens in South Africa. We suggest that these species should be considered the
      same-at least functionally-and global quarantine and management strategies
      applied equally to these Bactrocera species.

PMID- 24587235
TI  - Modulation of basophils' degranulation and allergy-related enzymes by monomeric
      and dimeric naphthoquinones.
AB  - Allergic disorders are characterized by an abnormal immune response towards non
      infectious substances, being associated with life quality reduction and potential
      life-threatening reactions. The increasing prevalence of allergic disorders
      demands for new and effective anti-allergic treatments. Here we test the anti
      allergic potential of monomeric (juglone, menadione, naphthazarin, plumbagin) and
      dimeric (diospyrin and diosquinone) naphthoquinones. Inhibition of RBL-2H3 rat
      basophils' degranulation by naphthoquinones was assessed using two complementary
      stimuli: IgE/antigen and calcium ionophore A23187. Additionally, we tested for
      the inhibition of leukotrienes production in IgE/antigen-stimulated cells, and
      studied hyaluronidase and lipoxidase inhibition by naphthoquinones in cell-free
      assays. Naphthazarin (0.1 uM) decreased degranulation induced by IgE/antigen but
      not A23187, suggesting a mechanism upstream of the calcium increase, unlike
      diospyrin (10 uM) that reduced degranulation in A23187-stimulated cells.
      Naphthoquinones were weak hyaluronidase inhibitors, but all inhibited soybean
      lipoxidase with the most lipophilic diospyrin, diosquinone and menadione being
      the most potent, thus suggesting a mechanism of competition with natural
      lipophilic substrates. Menadione was the only naphthoquinone reducing leukotriene
      C4 production, with a maximal effect at 5 uM. This work expands the current
      knowledge on the biological properties of naphthoquinones, highlighting
      naphthazarin, diospyrin and menadione as potential lead compounds for structural
      modification in the process of improving and developing novel anti-allergic
      drugs. 

PMID- 24587236
TI  - Metabotyping of docosahexaenoic acid - treated Alzheimer's disease cell model.
AB  - BACKGROUND: Despite the significant amount of work being carried out to
      investigate the therapeutic potential of docosahexaenoic acid (DHA) in
      Alzheimer's disease (AD), the mechanism by which DHA affects amyloid-beta
      precursor protein (AbetaPP)-induced metabolic changes has not been studied.
      OBJECTIVE: To elucidate the metabolic phenotypes (metabotypes) associated with
      DHA therapy via metabonomic profiling of an AD cell model using gas
      chromatography time-of-flight mass spectrometry (GC/TOFMS). METHODS: The lysate
      and supernatant samples of CHO-wt and CHO-AbetaPP695 cells treated with DHA and
      vehicle control were collected and prepared for GC/TOFMS metabonomics profiling.
      The metabolic profiles were analyzed by multivariate data analysis techniques
      using SIMCA-P+ software. RESULTS: Both principal component analysis and
      subsequent partial least squares discriminant analysis revealed distinct
      metabolites associated with the DHA-treated and control groups. A list of
      statistically significant marker metabolites that characterized the metabotypes
      associated with DHA treatment was further identified. Increased levels of
      succinic acid, citric acid, malic acid and glycine and decreased levels of
      zymosterol, cholestadiene and arachidonic acid correlated with DHA treatment
      effect. DHA levels were also found to be increased upon treatment. CONCLUSION:
      Our study shows that DHA plays a role in mitigating AbetaPP-induced impairment in
      energy metabolism and inflammation by acting on tricarboxylic acid cycle,
      cholesterol biosynthesis pathway and fatty acid metabolism. The perturbations of
      these metabolic pathways by DHA in CHO-wt and CHO-AbetaPP695 cells shed further
      mechanistic insights on its neuroprotective actions.

PMID- 24587237
TI  - Intraoperative cardiac arrest and mortality in trauma patients. A 14-yr survey
      from a Brazilian tertiary teaching hospital.
AB  - BACKGROUND: Little information on the factors influencing intraoperative cardiac
      arrest and its outcomes in trauma patients is available. This survey evaluated
      the associated factors and outcomes of intraoperative cardiac arrest in trauma
      patients in a Brazilian teaching hospital between 1996 and 2009. METHODS: Cardiac
      arrest during anesthesia in trauma patients was identified from an anesthesia
      database. The data collected included patient demographics, ASA physical status
      classification, anesthesia provider information, type of surgery, surgical areas
      and outcome. All intraoperative cardiac arrests and deaths in trauma patients
      were reviewed and grouped by associated factors and also analyzed as totally
      anesthesia-related, partially anesthesia-related, totally surgery-related or
      totally trauma patient condition-related. FINDINGS: Fifty-one cardiac arrests and
      42 deaths occurred during anesthesia in trauma patients. They were associated
      with male patients (P<0.001) and young adults (18-35 years) (P=0.04) with ASA
      physical status IV or V (P<0.001) undergoing gastroenterological or multiclinical
      surgeries (P<0.001). Motor vehicle crashes and violence were the main causes of
      trauma (P<0.001). Uncontrolled hemorrhage or head injury were the most
      significant associated factors of intraoperative cardiac arrest and mortality
      (P<0.001). All cardiac arrests and deaths reported were totally related to trauma
      patient condition. CONCLUSIONS: Intraoperative cardiac arrest and mortality
      incidence was highest in male trauma patients at a younger age with poor clinical
      condition, mainly related to uncontrolled hemorrhage and head injury, resulted
      from motor vehicle accidents and violence.

PMID- 24587238
TI  - Peripapillary retinoschisis in glaucomatous eyes.
AB  - PURPOSE: To investigate the structural and clinical characteristics of
      peripapillary retinoschisis observed in glaucomatous eyes using spectral-domain
      optical coherence tomography (SD-OCT). METHODS: Circumpapillary retinal nerve
      fiber layer (cpRNFL) and macular cross-hair SD-OCT scans and infrared fundus
      images of the glaucoma patients from the Investigating Glaucoma Progression Study
      (IGPS) and healthy volunteers were reviewed. Optic disc images obtained using
      enhanced depth imaging (EDI) SD-OCT were also evaluated. The structural
      characteristics and clinical course of the retinoschisis associated with glaucoma
      were investigated. RESULTS: Twenty-five retinoschisis areas were found in 22 of
      the 372 patients (5.9%) included in the IGPS, and in 1 area in 1 of 187 healthy
      control subjects (0.5%). In the 22 glaucomatous eyes with retinoschisis, the
      schisis was attached to the optic disc and overlapped with the retinal nerve
      fiber layer (RNFL) defect. The RNFL was the layer most commonly affected by the
      retinoschisis, either alone or together with other deeper layers. Acquired optic
      disc pit was identified in 8 eyes on disc photography and/or B-scan images
      obtained by EDI SD-OCT. Spontaneous resolution of this condition was observed in
      nine eyes. No retinal detachment or macular involvement of the retinoschisis was
      observed in any of the eyes. Multivariate analysis showed a significant influence
      of a higher intraocular pressure at SD-OCT scanning on the presence of
      retinoschisis (Odds ratio  = 1.418, P = 0.001). CONCLUSIONS: The present study
      investigated 22 cases of peripapillary retinoschisis in glaucomatous eyes. The
      retinoschisis was attached to the optic nerve and topographically correlated with
      RNFL defect. It often resolved spontaneously without causing severe visual
      disturbance. Care should be taken not to overestimate the RNFL thickness in eyes
      with retinoschisis, and also not to misinterpret the resolution of retinoschisis
      as a rapid glaucomatous RNFL deterioration.

PMID- 24587239
TI  - Is financial hardship associated with reduced health in disability? The case of
      spinal cord injury in Switzerland.
AB  - OBJECTIVE: To investigate socioeconomic inequalities in a comprehensive set of
      health indicators among persons with spinal cord injury in a wealthy country,
      Switzerland. METHODS: Observational cross-sectional data from 1549 participants
      of the Swiss Spinal Cord Injury Cohort Study (SwiSCI), aged over 16 years, and
      living in Switzerland were analyzed. Socioeconomic circumstances were
      operationalized by years of formal education, net equivalent household income and
      financial hardship. Health indicators including secondary conditions,
      comorbidities, pain, mental health, participation and quality of life were used
      as outcomes. Associations between socioeconomic circumstances and health
      indicators were evaluated using ordinal regressions. RESULTS: Financial hardship
      was consistently associated with more secondary conditions (OR 3.37, 95% CI 2.18
      5.21), comorbidities (OR 2.88, 95% CI 1.83-4.53) and pain (OR 3.32, 95% CI 2.21
      4.99), whereas mental health (OR 0.23, 95% CI 0.15-0.36), participation (OR 0.30,
      95% CI 0.21-0.43) and quality of life (OR 0.22, 95% CI 0.15-0.33) were reduced.
      Persons with higher education reported better mental health (OR 1.04, 95% CI 1.00
      1.07) and higher quality of life (OR 1.06, 95% CI 1.02-1.09); other health
      indicators were not associated with education. Household income was not related
      to any of the studied health indicators when models were controlled for financial
      hardship. CONCLUSIONS: Suffering from financial hardship goes along with
      significant reductions in physical health, functioning and quality of life, even
      in a wealthy country with comprehensive social and health policies.

PMID- 24587240
TI  - Development of a lozenge for oral transmucosal delivery of trans-resveratrol in
      humans: proof of concept.
AB  - Resveratrol provides multiple physiologic benefits which promote healthspan in
      various model species and clinical trials support continued exploration of
      resveratrol treatment in humans. However, there remains concern regarding low
      bioavailability and wide inter-individual differences in absorption and
      metabolism in humans, which suggests a great need to develop novel methods for
      resveratrol delivery. We hypothesized that oral transmucosal delivery, using a
      lozenge composed of a resveratrol-excipient matrix, would allow resveratrol to be
      absorbed rapidly into the bloodstream. We pursued proof of concept through two
      experiments. In the first experiment, the solubility of trans-resveratrol (tRES)
      in water and 2.0 M solutions of dextrose, fructose, ribose, sucrose, and xylitol
      was determined using HPLC. Independent t-tests with a Bonferroni correction were
      used to compare the solubility of tRES in each of the solutions to that in water.
      tRES was significantly more soluble in the ribose solution (p = 0.0013) than in
      the other four solutions. Given the enhanced solubility of tRES in a ribose
      solution, a resveratrol-ribose matrix was developed into a lozenge suitable for
      human consumption. Lozenges were prepared, each containing 146+/-5.5 mg tRES per
      2000 mg of lozenge mass. Two healthy human participants consumed one of the
      prepared lozenges following an overnight fast. Venipuncture was performed
      immediately before and 15, 30, 45, and 60 minutes following lozenge
      administration. Maximal plasma concentrations (Cmax) for tRES alone (i.e.,
      resveratrol metabolites not included) were 325 and 332 ng?mL(-1) for the two
      participants at 15 minute post-administration for both individuals. These results
      suggest a resveratrol-ribose matrix lozenge can achieve greater Cmax and enter
      the bloodstream faster than previously reported dosage forms for gastrointestinal
      absorption. While this study is limited by small sample size and only one method
      of resveratrol delivery, it does provide proof of concept to support further
      exploration of novel delivery methods for resveratrol administration.

PMID- 24587241
TI  - Anatomical transcriptome of G protein-coupled receptors leads to the
      identification of a novel therapeutic candidate GPR52 for psychiatric disorders.
AB  - Many drugs of abuse and most neuropharmacological agents regulate G protein
      coupled receptors (GPCRs) in the central nervous system (CNS)_ENREF_1. The
      striatum, in which dopamine D1 and D2 receptors are enriched, is strongly
      innervated by the ventral tegmental area (VTA), which is the origin of
      dopaminergic cell bodies of the mesocorticolimbic dopamine system_ENREF_3 and
      plays a central role in the development of psychiatric disorders_ENREF_4. Here we
      report the comprehensive and anatomical transcript profiling of 322 non-odorant
      GPCRs in mouse tissue by quantitative real-time PCR (qPCR), leading to the
      identification of neurotherapeutic receptors exclusively expressed in the CNS,
      especially in the striatum. Among them, GPR6, GPR52, and GPR88, known as orphan
      GPCRs, were shown to co-localize either with a D2 receptor alone or with both D1
      and D2 receptors in neurons of the basal ganglia. Intriguingly, we found that
      GPR52 was well conserved among vertebrates, is Gs-coupled and responsive to the
      antipsychotic drug, reserpine. We used three types of transgenic (Tg) mice
      employing a Cre-lox system under the control of the GPR52 promoter, namely, GPR52
      LacZ Tg, human GPR52 (hGPR52) Tg, and hGPR52-GFP Tg mice. Detailed histological
      investigation suggests that GPR52 may modulate dopaminergic and glutamatergic
      transmission in neuronal circuits responsible for cognitive function and emotion.
      In support of our prediction, GPR52 knockout and transgenic mice exhibited
      psychosis-related and antipsychotic-like behaviors, respectively. Therefore, we
      propose that GPR52 has the potential of being a therapeutic psychiatric receptor.
      This approach may help identify potential therapeutic targets for CNS diseases. 

PMID- 24587242
TI  - High glucose level promotes migration behavior of breast cancer cells through
      zinc and its transporters.
AB  - BACKGROUND: The diabetes patients have been associated with an increased risk of
      mortality by breast cancer and there are difference between the breast cancer
      patients with diabetes, and their nondiabetic counterparts in the regimen choice
      and effects of breast cancer treatment. However, the pathophysiological
      relationships of diabetes and breast cancer have not yet been elucidated in
      detail. In this study, we investigate the breast cancer cell line, MCF-7
      motility, which linked to invasion and metastasis, in high glucose level
      corresponding to hyperglycemia and the role of Zn and its transporter.
      METHODOLOGY/PRINCIPAL FINDINGS: We demonstrated the significant motility of MCF-7
      cultured in hyperglycemic level (25 mM glucose) in comparison to normal
      physiological glucose level (5.5 mM glucose). The other hand, the osmotic control
      medium, 5.5 mM glucose with 19.5 mM mannitol or fructose had no effect on
      migratory, suggesting that high glucose level promotes the migration of MCF-7.
      Moreover, the activity of intracellular Zn(2+) uptake significantly increased in
      high glucose-treated cells in comparison to 5.5 mM glucose, and the mRNA
      expression of zinc transporters, ZIP6 and ZIP10, was upregulated in 25 mM glucose
      treated cells. The deficiency of ZIP6 or ZIP10 and intracellular Zn(2+)
      significantly inhibited the high migration activity in 25 mM glucose medium,
      indicating that Zn(2+) transported via ZIP6 and ZIP10 play an essential role in
      the promotion of cell motility by high glucose stimulation.
      CONCLUSION/SIGNIFICANCE: Zinc and its transporters, ZIP6 and ZIP10, are required
      for the motility stimulated with high glucose level. These findings provide the
      first evidence proposing the novel strategies for the diagnosis and therapy of
      breast cancer with hyperglycemia.

PMID- 24587243
TI  - Intertemporal choice as discounted value accumulation.
AB  - Two separate cognitive processes are involved in choosing between rewards
      available at different points in time. The first is temporal discounting, which
      consists of combining information about the size and delay of prospective rewards
      to represent subjective values. The second involves a comparison of available
      rewards to enable an eventual choice on the basis of these subjective values.
      While several mathematical models of temporal discounting have been developed,
      the reward selection process has been largely unexplored. To address this
      limitation, we evaluated the applicability of the Linear Ballistic Accumulator
      (LBA) model as a theory of the selection process in intertemporal choice. The LBA
      model formalizes the selection process as a sequential sampling algorithm in
      which information about different choice options is integrated until a decision
      criterion is reached. We compared several versions of the LBA model to
      demonstrate that choice outcomes and response times in intertemporal choice are
      well captured by the LBA process. The relationship between choice outcomes and
      response times that derives from the LBA model cannot be explained by temporal
      discounting alone. Moreover, the drift rates that drive evidence accumulation in
      the best-fitting LBA model are related to independently estimated subjective
      values derived from various temporal discounting models. These findings provide a
      quantitative framework for predicting dynamics of choice-related activity during
      the reward selection process in intertemporal choice and link intertemporal
      choice to other classes of decisions in which the LBA model has been applied. 

PMID- 24587244
TI  - A novel growing device inspired by plant root soil penetration behaviors.
AB  - Moving in an unstructured environment such as soil requires approaches that are
      constrained by the physics of this complex medium and can ensure energy
      efficiency and minimize friction while exploring and searching. Among living
      organisms, plants are the most efficient at soil exploration, and their roots
      show remarkable abilities that can be exploited in artificial systems. Energy
      efficiency and friction reduction are assured by a growth process wherein new
      cells are added at the root apex by mitosis while mature cells of the root remain
      stationary and in contact with the soil. We propose a new concept of root-like
      growing robots that is inspired by these plant root features. The device
      penetrates soil and develops its own structure using an additive layering
      technique: each layer of new material is deposited adjacent to the tip of the
      device. This deposition produces both a motive force at the tip and a hollow
      tubular structure that extends to the surface of the soil and is strongly
      anchored to the soil. The addition of material at the tip area facilitates soil
      penetration by omitting peripheral friction and thus decreasing the energy
      consumption down to 70% comparing with penetration by pushing into the soil from
      the base of the penetration system. The tubular structure provides a path for
      delivering materials and energy to the tip of the system and for collecting
      information for exploratory tasks. 

PMID- 24587246
TI  - Genetic inheritance of female and male morphotypes in giant freshwater prawn
      Macrobrachium rosenbergii.
AB  - Giant freshwater prawn (GFP) Macrobrachium rosenbergii is unique with males
      categorized in five different morphotypes (small claw, orange claw, blue claw,
      old blue claw and no claw males) and females in three reproductive statuses
      (mature ovary, berried and spawned females). In the present study we examined
      genetic inheritance of female and male morphotypes, their body weights and
      genetic associations between morphotypes and body traits. Restricted maximum
      likelihood fitting a multi-trait animal model was performed on a total of 21,459
      body records collected over five generations in a GFP population selected for
      high growth rate. The estimates of variance components showed that there were
      substantial differences in additive genetic variance in body weight between male
      morphotypes. The low and significantly different from one genetic correlations
      between the expressions of body weight in male morphotypes also suggest that
      these traits should be treated as genetically different traits in selective
      breeding programs. By contrast, body weights of female types are essentially the
      same characters as indicated by the high genetic correlations between homologous
      trait expressions. In addition to body weight, male morphotypes and female
      reproductive statuses were treated as traits in themselves and were analysed as
      binary observations using animal and sire linear mixed models, and logit and
      probit threshold models. The estimates of heritability back-transformed from the
      liability scale were in good agreement with those obtained from linear mixed
      models, ranging from 0.02 to 0.43 for male morphotypes and 0.06 to 0.10 for
      female types. The genetic correlations among male morphoptypes were generally
      favourable. Body weight showed negative genetic associations with SM (-0.96),
      whereas those of body weight with other male morphotypes were positive (0.25 to
      0.76). Our results showed that there is existence of heritable (additive genetic)
      component for male morphotypes, giving prospects for genetic selection to change
      population structure of GFP. 

PMID- 24587245
TI  - Stathmin protein level, a potential predictive marker for taxane treatment
      response in endometrial cancer.
AB  - Stathmin is a prognostic marker in many cancers, including endometrial cancer.
      Preclinical studies, predominantly in breast cancer, have suggested that stathmin
      may additionally be a predictive marker for response to paclitaxel. We first
      evaluated the response to paclitaxel in endometrial cancer cell lines before and
      after stathmin knock-down. Subsequently we investigated the clinical response to
      paclitaxel containing chemotherapy in metastatic endometrial cancer in relation
      to stathmin protein level in tumors. Stathmin level was also determined in
      metastatic lesions, analyzing changes in biomarker status on disease progression.
      Knock-down of stathmin improved sensitivity to paclitaxel in endometrial
      carcinoma cell lines with both naturally higher and lower sensitivity to
      paclitaxel. In clinical samples, high stathmin level was demonstrated to be
      associated with poor response to paclitaxel containing chemotherapy and to
      reduced disease specific survival only in patients treated with such combination.
      Stathmin level increased significantly from primary to metastatic lesions. This
      study suggests, supported by both preclinical and clinical data, that stathmin
      could be a predictive biomarker for response to paclitaxel treatment in
      endometrial cancer. Re-assessment of stathmin level in metastatic lesions prior
      to treatment start may be relevant. Also, validation in a randomized clinical
      trial will be important. 

PMID- 24587247
TI  - A new QTL for plant height in barley (Hordeum vulgare L.) showing no negative
      effects on grain yield.
AB  - INTRODUCTION: Reducing plant height has played an important role in improving
      crop yields. The success of a breeding program relies on the source of dwarfing
      genes. For a dwarfing or semi-dwarfing gene to be successfully used in a breeding
      program, the gene should have minimal negative effects on yield and perform
      consistently in different environments. METHODS: In this study, 182 doubled
      haploid lines, generated from a cross between TX9425 and Naso Nijo, were grown in
      six different environments to identify quantitative trait loci (QTL) controlling
      plant height and investigate QTL * environments interaction. RESULTS: A QTL for
      plant was identified on 7H. This QTL showed no significant effects on other
      agronomic traits and yield components and consistently expressed in the six
      environments. A sufficient allelic effect makes it possible for this QTL to be
      successfully used in breeding programs.

PMID- 24587248
TI  - Mebendazole reduces vascular smooth muscle cell proliferation and neointimal
      formation following vascular injury in mice.
AB  - Mebendazole is an antihelminthic drug that exerts its effects via interference
      with microtubule function in parasites. To determine the utility of mebendazole
      as a potential treatment for vascular diseases involving proliferation of
      vascular smooth muscle cells, the effects of mebendazole on vascular smooth
      muscle cell proliferation were tested in vitro and in a mouse model of arterial
      injury. In vitro, mebendazole inhibited proliferation and migration of murine
      vascular smooth muscle cells and this was associated with altered intracellular
      microtubule organization. To determine in vivo effects of mebendazole following
      vascular injury, femoral arterial wire injury was induced in wild-type mice
      treated with either mebendazole or placebo control. Compared with placebo-treated
      mice, mebendazole-treated mice formed less neointima at the site of injury.
      Mebendazole is effective at inhibiting vascular smooth muscle cell proliferation
      and migration, and neointimal formation following arterial injury in mice. 

PMID- 24587249
TI  - Impact of Campylobacter jejuni cj0268c knockout mutation on intestinal
      colonization, translocation, and induction of immunopathology in gnotobiotic IL
      10 deficient mice.
AB  - BACKGROUND: Although Campylobacter jejuni infections have a high prevalence
      worldwide and represent a significant socioeconomic burden, the underlying
      molecular mechanisms of induced intestinal immunopathology are still not well
      understood. We have recently generated a C. jejuni mutant strain
      NCTC11168::cj0268c, which has been shown to be involved in cellular adhesion and
      invasion. The immunopathological impact of this gene, however, has not been
      investigated in vivo so far. METHODOLOGY/PRINCIPAL FINDINGS: Gnotobiotic IL-10
      deficient mice were generated by quintuple antibiotic treatment and perorally
      infected with C. jejuni mutant strain NCTC11168::cj0268c, its complemented
      version (NCTC11168::cj0268c-comp-cj0268c), or the parental strain NCTC11168.
      Kinetic analyses of fecal pathogen loads until day 6 post infection (p.i.)
      revealed that knockout of cj0268c did not compromise intestinal C. jejuni
      colonization capacities. Whereas animals irrespective of the analysed C. jejuni
      strain developed similar clinical symptoms of campylobacteriosis (i.e.
      enteritis), mice infected with the NCTC11168::cj0268c mutant strain displayed
      significant longer small as well as large intestinal lengths indicative for less
      distinct C. jejuni induced pathology when compared to infected control groups at
      day 6 p.i. This was further supported by significantly lower apoptotic and T cell
      numbers in the colonic mucosa and lamina propria, which were paralleled by lower
      intestinal IFN-gamma and IL-6 concentrations at day 6 following knockout mutant
      NCTC11168::cj0268c as compared to parental strain infection. Remarkably, less
      intestinal immunopathology was accompanied by lower IFN-gamma secretion in ex
      vivo biopsies taken from mesenteric lymphnodes of NCTC11168::cj0268c infected
      mice versus controls. CONCLUSION/SIGNIFICANCE: We here for the first time show
      that the cj0268c gene is involved in mediating C. jejuni induced
      immunopathogenesis in vivo. Future studies will provide further deep insights
      into the immunological and molecular interplays between C. jejuni and innate
      immunity in human campylobacteriosis.

PMID- 24587250
TI  - The correlation between pro- and anti-inflammatory cytokines in chronic subdural
      hematoma patients assessed with factor analysis.
AB  - Chronic subdural hematoma (CSDH) is a relatively common disorder in neurosurgery
      on elderly patients, though the mechanism that causes the disease remains
      unclear. Studies have suggested that local anticoagulation and inflammatory
      changes may be important in its pathogenesis. Most studies have used a basic
      bivariate statistical analysis to assess complex immunological responses in
      patients with this disorder, hence a more sophisticated multivariate statistical
      approach might be warranted. Our objective was to assess the association and
      correlation between the pro- and anti-inflammatory responses in a cohort of
      patients with chronic subdural hematoma (n=57) using an exploratory and
      confirmatory factor analysis. Thirteen assigned pro-inflammatory (TNF-alpha, IL
      1beta, IL-2, IL-2R, IL-6, IL-7, IL-12, IL-15, IL-17, CCL2, CXCL8, CXCL9 and
      CXCL10) and five assigned anti-inflammatory (IL-1RA, IL-4, IL-5, IL-10 and IL-13)
      cytokines from blood and hematoma fluid samples were examined. Exploratory factor
      analysis indicated two major underlying immunological processes expressed by the
      cytokines in both blood and hematoma fluid, but with a different pattern and
      particularly regarding the cytokines IL-13, IL-6, IL-4 and TNF-alpha. Scores from
      confirmatory factor analysis models exhibited a higher correlation between pro-
      and anti-inflammatory activities in blood (r=0.98) than in hematoma fluid samples
      (r=0.92). However, correlations of inflammatory processes between blood and
      hematoma fluid samples were lower and non-significant. A structural equation
      model showed a significant association between increased anti-inflammatory
      activity in hematoma fluid samples and a lower risk of recurrence, but this
      relationship was not statistically significant in venous blood samples. Moreover,
      these findings indicate that anti-inflammatory activities in the hematoma may
      play a role in the risk of a recurrence of CSDH.

PMID- 24587251
TI  - The muscle oxidative regulatory response to acute exercise is not impaired in
      less advanced COPD despite a decreased oxidative phenotype.
AB  - Already in an early disease stage, patients with chronic obstructive pulmonary
      disease (COPD) are confronted with impaired skeletal muscle function and physical
      performance due to a loss of oxidative type I muscle fibers and oxidative
      capacity (i.e. oxidative phenotype; Oxphen). Physical activity is a well-known
      stimulus of muscle Oxphen and crucial for its maintenance. We hypothesized that a
      blunted response of Oxphen genes to an acute bout of exercise could contribute to
      decreased Oxphen in COPD. For this, 28 patients with less advanced COPD (age 65
      +/- 7 yrs, FEV1 59 +/- 16% predicted) and 15 age- and gender-matched healthy
      controls performed an incremental cycle ergometry test. The Oxphen response to
      exercise was determined by the measurement of gene expression levels of Oxphen
      markers in pre and 4h-post exercise quadriceps biopsies. Because exercise-induced
      hypoxia and oxidative stress may interfere with Oxphen response, oxygen
      saturation and oxidative stress markers were assessed as well. Regardless of
      oxygen desaturation and absolute exercise intensities, the Oxphen regulatory
      response to exercise was comparable between COPD patients and controls with no
      evidence of increased oxidative stress. In conclusion, the muscle Oxphen
      regulatory response to acute exercise is not blunted in less advanced COPD,
      regardless of exercise-induced hypoxia. Hence, this study provides further
      rationale for incorporation of exercise training as integrated part of disease
      management to prevent or slow down loss of muscle Oxphen and related functional
      impairment in COPD.

PMID- 24587252
TI  - Ambra1 is an essential regulator of autophagy and apoptosis in SW620 cells: pro
      survival role of Ambra1.
AB  - Recent research has revealed a role for Ambra1, an autophagy-related gene-related
      (ATG) protein, in the autophagic pro-survival response, and Ambra1 has been shown
      to regulate Beclin1 and Beclin1-dependent autophagy in embryonic stem cells.
      However, whether Ambra1 plays an important role in the autophagy pathway in
      colorectal cancer cells is unknown. In this study, we hypothesized that Ambra1 is
      an important regulator of autophagy and apoptosis in CRC cell lines. To test this
      hypothesis, we confirmed autophagic activity in serum-starved SW620 CRC cells by
      assessing endogenous microtubule-associated protein 1 light chain 3 (LC3)
      localization, the presence of autophagosomes (transmission electron microscopy)
      and LC3 protein levels (Western blotting). Ambra1 expression was detected by
      Western blot in SW620 cells treated with staurosporine or etoposide. Calpain and
      caspase inhibitors were employed to verify whether calpains and caspases were
      responsible for Ambra1 cleavage. To examine the role of Ambra1 in apoptosis,
      Ambra1 knockdown cells were treated with staurosporine and etoposide. Cell
      apoptosis and viability were measured by annexin-V and PI staining and MTT
      assays. We determined that serum deprivation-induced autophagy was associated
      with Ambra1 upregulation in colorectal cancer cell lines. Ambra1 expression
      decreased during staurosporine- or etoposide-induced apoptosis. Calpains and
      caspases may be responsible for Ambra1 degradation. When Ambra1 expression was
      reduced by siRNA, SW620 cells were more sensitive to staurosporine- or etoposide
      induced apoptosis. In addition, starvation-induced autophagy decreased. Finally,
      Co-immunoprecipitation of Ambra1 and Beclin1 demonstrated that Ambra1 and Beclin1
      interact in serum-starved or rapamycin-treated SW620 cells, suggesting that
      Ambra1 regulates autophagy in CRC cells by interacting with Beclin1. In
      conclusion, Ambra1 is a crucial regulator of autophagy and apoptosis in CRC cells
      that maintains the balance between autophagy and apoptosis. 

PMID- 24587253
TI  - Natural diet of coral-excavating sponges consists mainly of dissolved organic
      carbon (DOC).
AB  - Coral-excavating sponges are the most important bioeroders on Caribbean reefs and
      increase in abundance throughout the region. This increase is commonly attributed
      to a concomitant increase in food availability due to eutrophication and
      pollution. We therefore investigated the uptake of organic matter by the two
      coral-excavating sponges Siphonodictyon sp. and Cliona delitrix and tested
      whether they are capable of consuming dissolved organic carbon (DOC) as part of
      their diet. A device for simultaneous sampling of water inhaled and exhaled by
      the sponges was used to directly measure the removal of DOC and bacteria in situ.
      During a single passage through their filtration system 14% and 13% respectively
      of the total organic carbon (TOC) in the inhaled water was removed by the
      sponges. 82% (Siphonodictyon sp.; mean +/- SD; 13 +/- 17 MUmol L(-1)) and 76% (C.
      delitrix; 10 +/- 12 MUmol L(-1)) of the carbon removed was taken up in form of
      DOC, whereas the remainder was taken up in the form of particulate organic carbon
      (POC; bacteria and phytoplankton) despite high bacteria retention efficiency (72
      +/- 15% and 87 +/- 10%). Siphonodictyon sp. and C. delitrix removed DOC at a rate
      of 461 +/- 773 and 354 +/- 562 MUmol C h(-1) respectively. Bacteria removal was
      1.8 +/- 0.9 * 10(10) and 1.7 +/- 0.6 * 10(10) cells h(-1), which equals a carbon
      uptake of 46.0 +/- 21.2 and 42.5 +/- 14.0 MUmol C h(-1) respectively. Therefore,
      DOC represents 83 and 81% of the TOC taken up by Siphonodictyon sp. and C.
      delitrix per hour. These findings suggest that similar to various reef sponges
      coral-excavating sponges also mainly rely on DOC to meet their carbon demand. We
      hypothesize that excavating sponges may also benefit from an increasing
      production of more labile algal-derived DOC (as compared to coral-derived DOC) on
      reefs as a result of the ongoing coral-algal phase shift.

PMID- 24587254
TI  - Regulation of p53 level by UBE4B in breast cancer.
AB  - p53 is possibly the most important mammalian tumor suppressor and it is mutated
      or lost in more than half of all human cancers. The stability of p53 is primarily
      determined by the RING domain E3 ubiquitin ligase Hdm2, which targets p53 for
      proteasomal degradation, restraining the potent activity of p53 and enabling cell
      survival and proliferation. UBE4B has been shown to physically interact with p53
      and Hdm2 and to negatively regulate p53 stability and function. However, no one
      has determined whether UBE4B promotes p53 degradation in breast cancer. In this
      study, UBE4B promoted the degradation and ubiquitination of p53 to inhibit the
      apoptosis of cancer cells and promote tumorigenesis. Our results indicate that
      UBE4B regulates p53 in breast cancer and could be a viable target for developing
      new therapeutic strategies for breast cancer treatment. 

PMID- 24587255
TI  - A compensatory role of NF-kappaB to p53 in response to 5-FU-based chemotherapy
      for gastric cancer cell lines.
AB  - Despite of remarkable improvement of postoperative 5-FU-based adjuvant
      chemotherapy, the relapse rate of gastric cancer patients who undergo curative
      resection followed by the adjuvant chemotherapy remains substantial. Therefore,
      it is important to identify prediction markers for the chemotherapeutic efficacy
      of 5-FU. We recently identified NF-kappaB as a candidate relapse prediction
      biomarker in gastric cancer. To evaluate the biological significance of NF-kappaB
      in the context of 5-FU-based chemotherapy, we analyzed the NF-kappaB-dependent
      biological response upon 5-FU treatment in gastric cancer cell lines. Seven genes
      induced by 5-FU treatment in an NF-kappaB-dependent manner were identified, five
      of which are known p53 targets. Knockdown of RELA, which encodes the p65 subunit
      of NF-kappaB, decreased both p53 and p53 target protein levels. In contrast, NF
      kappaB was not affected by TP53 knockdown. We also demonstrated that cell lines
      bearing Pro/Pro homozygosity in codon72 of p53 exon4, which is important for NF
      kappaB binding to p53, are more resistant to 5-FU than those with Arg/Arg
      homozygosity. We conclude that NF-kappaB plays an important role in the response
      to 5-FU treatment in gastric cancer cell lines, with a possible compensatory
      function of p53. These results suggest that NF-kappaB is a potential 5-FU
      chemosensitivity prediction marker that may reflect 5-FU-induced stress-response
      pathways, including p53. 

PMID- 24587256
TI  - Advances toward the elucidation of hypertonic saline effects on Pseudomonas
      aeruginosa from cystic fibrosis patients.
AB  - OBJECTIVES: Nebulized hypertonic saline (HTS) has beneficial effects including
      reducing pulmonary exacerbations in Cystic Fibrosis (CF) patients. Several
      mechanisms may explain these effects but antimicrobial activity of NaCl remains
      largely unexplored. We aimed to measure the antimicrobial effect of NaCl on
      Pseudomonas aeruginosa isolated from the respiratory tract in CF patients.
      METHODS: NaCl minimal inhibitory concentration (MIC) and minimal bactericidal
      concentration (MBC) were determined for strains characterized for mucoidy,
      antimicrobial resistance, and ability to form biofilm using 0,9% to 15% NaCl
      solutions. NaCl effects on biofilm formation, preformed biofilm, and mobility
      were evaluated. Kinetics of antimicrobial effects was studied. RESULTS: The
      growth of all isolates (n = 85) from 34 patients was inhibited by 6% NaCl
      solution. A 10% concentration had a bactericidal activity on 90% of the isolates.
      Mucoid and multidrug resistant (MDR) isolates displayed lower MICs compared to
      non-mucoid and to non-MDR isolates, respectively. Time-kill kinetics showed that
      NaCl exhibited a rapid, dose and growth phase dependent bactericidal effect.
      Three percent or more of NaCl inhibited biofilm formation for 69% of strongly
      adherent isolates. A dose-dependent decrease of preformed biofilm viability and
      an inhibitory activity on bacterial motility were observed. CONCLUSIONS: NaCl
      inhibited the growth of all isolates and killed 38% of tested isolates within
      concentration range currently used in therapeutics. Our results suggest that anti
      pseudomonal activity is another mechanism of action of HTS to add to those
      already established. Clinical trials are needed to compare diverse HTS conditions
      of use (rhythm, dose and mode of delivery) to obtain efficient and optimized anti
      P. aeruginosa effects. More generally, NaCl effect on other opportunistic
      pathogens as well as on global microbiotae recovered during polymicrobial
      diseases warrants further investigations.

PMID- 24587257
TI  - The role of mutation rate variation and genetic diversity in the architecture of
      human disease.
AB  - BACKGROUND: We have investigated the role that the mutation rate and the
      structure of genetic variation at a locus play in determining whether a gene is
      involved in disease. We predict that the mutation rate and its genetic diversity
      should be higher in genes associated with disease, unless all genes that could
      cause disease have already been identified. RESULTS: Consistent with our
      predictions we find that genes associated with Mendelian and complex disease are
      substantially longer than non-disease genes. However, we find that both Mendelian
      and complex disease genes are found in regions of the genome with relatively low
      mutation rates, as inferred from intron divergence between humans and
      chimpanzees, and they are predicted to have similar rates of non-synonymous
      mutation as other genes. Finally, we find that disease genes are in regions of
      significantly elevated genetic diversity, even when variation in the rate of
      mutation is controlled for. The effect is small nevertheless. CONCLUSIONS: Our
      results suggest that gene length contributes to whether a gene is associated with
      disease. However, the mutation rate and the genetic architecture of the locus
      appear to play only a minor role in determining whether a gene is associated with
      disease.

PMID- 24587258
TI  - Overweight, obesity and meningioma risk: a meta-analysis.
AB  - BACKGROUND AND OBJECTIVES: Studies of the association between excess body weight
      and risk of meningioma have produced inconsistent results. Therefore, a meta
      analysis of published studies was performed to better assess the association
      between meningioma and excess body weight. METHODS: A literature search was
      conducted in the PubMed and EMBASE databases without any limitations. The
      reference lists of identified articles were also screened for additional studies.
      The summary relative risks (RRs) and 95% confidence intervals (CI) were
      calculated using fixed- or random-effects models. RESULTS: A total of 6 studies
      provided risk estimates for overweight or obesity. Overall, the combined RRs were
      1.12 (95% CI = 0.98-1.28) for overweight and 1.45 (95% CI = 1.26-1.67) for
      obesity. After stratification by gender, no significant association was observed
      for obese men (RR = 1.30, 95% CI = 0.64-2.62), while significant association was
      detected for obese women (RR = 1.46, 95% CI = 1.26-1.69). No substantial
      differences emerged across strata of study design and geographic areas.
      CONCLUSION: The results of this meta-analysis suggest that obesity but not
      overweight is associated with an increased risk of meningioma. Due to the limited
      number of studies, further research is needed to confirm the association.

PMID- 24587259
TI  - Road salts as environmental constraints in urban pond food webs.
AB  - Freshwater salinization is an emerging environmental filter in urban aquatic
      ecosystems that receive chloride road salt runoff from vast expanses of
      impervious surface cover. Our study was designed to evaluate the effects of
      chloride contamination on urban stormwater pond food webs through changes in
      zooplankton community composition as well as density and biomass of primary
      producers and consumers. From May - July 2009, we employed a 2*2*2 full-factorial
      design to manipulate chloride concentration (low = 177 mg L(-1) Cl(-/)high = 1067
      mg L(-1) Cl(-)), gray treefrog (Hyla versicolor) tadpoles (presence/absence) and
      source of stormwater pond algae and zooplankton inoculum (low conductance/high
      conductance urban ponds) in 40, 600-L mesocosms. Road salt did serve as a
      constraint on zooplankton community structure, driving community divergence
      between the low and high chloride treatments. Phytoplankton biomass (chlorophyll
      [a] ug L(-1)) in the mesocosms was significantly greater for the high conductance
      inoculum (P<0.001) and in the high chloride treatment (P = 0.046), whereas
      periphyton biomass was significantly lower in the high chloride treatment (P =
      0.049). Gray treefrog tadpole time to metamorphosis did not vary significantly
      between treatments. However, mass at metamorphosis was greater among tadpoles
      that experienced a faster than average time to metamorphosis and exposure to high
      chloride concentrations (P = 0.039). Our results indicate differential
      susceptibility to chloride salts among algal resources and zooplankton taxa, and
      further suggest that road salts can act as a significant environmental constraint
      on urban stormwater pond communities. 

PMID- 24587260
TI  - Efficiency of lift production in flapping and gliding flight of swifts.
AB  - Many flying animals use both flapping and gliding flight as part of their routine
      behaviour. These two kinematic patterns impose conflicting requirements on wing
      design for aerodynamic efficiency and, in the absence of extreme morphing, wings
      cannot be optimised for both flight modes. In gliding flight, the wing
      experiences uniform incident flow and the optimal shape is a high aspect ratio
      wing with an elliptical planform. In flapping flight, on the other hand, the wing
      tip travels faster than the root, creating a spanwise velocity gradient. To
      compensate, the optimal wing shape should taper towards the tip (reducing the
      local chord) and/or twist from root to tip (reducing local angle of attack). We
      hypothesised that, if a bird is limited in its ability to morph its wings and
      adapt its wing shape to suit both flight modes, then a preference towards
      flapping flight optimization will be expected since this is the most
      energetically demanding flight mode. We tested this by studying a well-known flap
      gliding species, the common swift, by measuring the wakes generated by two birds,
      one in gliding and one in flapping flight in a wind tunnel. We calculated span
      efficiency, the efficiency of lift production, and found that the flapping swift
      had consistently higher span efficiency than the gliding swift. This supports our
      hypothesis and suggests that even though swifts have been shown previously to
      increase their lift-to-drag ratio substantially when gliding, the wing morphology
      is tuned to be more aerodynamically efficient in generating lift during flapping.
      Since body drag can be assumed to be similar for both flapping and gliding, it
      follows that the higher total drag in flapping flight compared with gliding
      flight is primarily a consequence of an increase in wing profile drag due to the
      flapping motion, exceeding the reduction in induced drag. 

PMID- 24587261
TI  - Molecular characterization and mapping of Fgf21 gene in a foodfish species asian
      seabass.
AB  - Fgf21 is a newly discovered fibroblast growth factor. It is typically induced by
      fasting and plays important roles in the regulation of glucose and lipid
      metabolisms and energy balance in mammals, whereas potential functions of this
      gene in teleosts are still unknown. We identified the Fgf21 gene and studied its
      functions in Asian seabass (Lates calcarifer). The cDNA of the Fgf21 encoded a
      protein with 206 amino acids. Analysis of DNA and amino acid sequences of Fgf21
      genes revealed that the sequences and structure of the Fgf21 genes were highly
      conserved in vertebrates. Real-time PCR revealed that Fgf21 was exclusively
      expressed in the intestine and kidney, which was different from the expression
      profiles of mammals. Fgf21 was down-regulated under fasting, whereas it was
      significantly increased during the LPS challenge. Exogenous recombinant FGF21
      significantly suppressed the appetite of Asian seabass. Our data suggest that
      Fgf21 plays a role in energy regulation and acute phase response in Asian
      seabass, and may have different functions in fish and mammals. In addition, we
      identified one SNP in Fgf21. By using this SNP, the gene was mapped on the
      linkage group 23, where a suggestive QTL for growth was mapped previously.
      Association mapping identified significant associations between Fgf21 genotypes
      at the SNP and growth traits. These results not only provide important
      information of the functions of Fgf21, but also suggest that the SNP in this gene
      can be used as a marker in selecting fast-growing individuals of Asian seabass. 

PMID- 24587262
TI  - Voriconazole or amphotericin B as primary therapy yields distinct early serum
      galactomannan trends related to outcomes in invasive aspergillosis.
AB  - An improved number of anti-fungal drugs are currently available for the treatment
      of invasive aspergillosis (IA). While serial galactomannan index (GMI)
      measurement can be used to monitor response to treatment, the extent to which
      different anti-fungal regimens can affect galactomannan levels is unknown. In 147
      IA patients receiving either voriconazole (VCZ) or conventional amphotericin B
      (CAB) in a multicentre clinical trial, we performed post-hoc analyses of GMI
      trends in relation to outcomes. The generalized estimation equations approach was
      used to estimate changes in the effect size for GMI over time within patients.
      Patients who received VCZ primary therapy and had good treatment response 12
      weeks later showed earlier decreases in GMI values at Week 1 and Week 2 (p =
      0.001 and 0.046 respectively) as compared to patients who only received CAB. At
      end-of-randomized therapy (EORT), which was a pre-set secondary assessment point
      for all patients who switched from randomized primary (CAB or VCZ) to an
      alternative anti-fungal drug, treatment failure was associated with increasing
      GMI at Weeks 1 and 2 in CAB-primary treated patients (p = 0.022 and 0.046
      respectively). These distinct trends highlight the variations in GMI kinetics
      with the use of different anti-fungal drugs and their implications in relation to
      IA treatment response.

PMID- 24587263
TI  - An integrative analysis of the dynamics of landscape- and local-scale
      colonization of Mediterranean woodlands by Pinus halepensis.
AB  - Afforestation efforts have resulted in extensive plantations of either native or
      non-native conifers, which in many regions has led to the spread of those
      conifers into surrounding natural vegetation. This process of species
      colonization can trigger profound changes in both community dynamics and
      ecosystem processes. Our study disentangled the complexity of a process of
      colonization in a heterogeneous landscape into a simple set of rules. We analyzed
      the factors that control the colonization of natural woodland ecosystems by Pinus
      halepensis dispersing from plantations in the Mediterranean region of Israel. We
      developed maximum-likelihood models to explain the densities of P. halepensis
      colonizing natural woodlands. Our models unravel how P. halepensis colonization
      is controlled by factors that determine colonization pressure by dispersing seeds
      and by factors that control resistance to colonization of the natural ecosystems.
      Our models show that the combination of different seed arrival processes from
      local, landscape, and regional scales determine pine establishment potential, but
      the relative importance of each component varied according to seed source
      distribution. Habitat resistance, determined by abiotic and biotic conditions,
      was as important as propagule input in determining the density of pine
      colonization. Thus, despite the fact that pine propagules disperse throughout the
      landscape, habitat heterogeneity within the natural ecosystems generates
      significant variation in the actual densities of colonized pine. Our approach
      provides quantitative measures of how processes at different spatial scales
      affect the distribution and densities of colonizing species, and a basis for
      projection of expected distributions. Variation in colonization rates, due to
      landscape-scale heterogeneity in both colonization pressure and resistance to
      colonization, can be expected to produce a diversity of new ecosystems. This work
      provides a template for understanding species colonization processes, especially
      in light of anthropogenic impacts, and predicting future transformation of
      natural ecosystems by species invasion. 

PMID- 24587264
TI  - Correlates of inappropriate prescribing of antibiotics to patients with malaria
      in Uganda.
AB  - BACKGROUND: In many rural areas of Uganda, febrile patients presenting to health
      facilities are prescribed both antimalarials and antibiotics, contributing to the
      overuse of antibiotics. We identified the prevalence and correlates of
      inappropriate antibiotic management of patients with confirmed malaria. METHODS:
      We utilized individual outpatient data from 36 health centers from January to
      September 2011. We identified patients who were prescribed antibiotics without an
      appropriate clinical indication, as well as patients who were not prescribed
      antibiotics when treatment was clinically indicated. Multivariate logistic
      regression models were used to identify clinical and operational factors
      associated with inappropriate case management. FINDINGS: Of the 45,591 patients
      with parasitological diagnosis of malaria, 40,870 (90%) did not have a clinical
      indication for antibiotic treatment. Within this group, 17,152 (42%) were
      inappropriately prescribed antibiotics. The odds of inappropriate prescribing
      were higher if the patient was less than five years old (aOR 1.96, 95% CI 1.75
      2.19) and if the health provider had the fewest years of training (aOR 1.86, 95%
      CI 1.05-3.29). The odds of inappropriate prescribing were lower if patients had
      emergency triage status (aOR 0.75, 95% CI 0.59-0.96) or were HIV positive (aOR
      0.31, 95% CI 0.20-0.45). Of the 4,721 (10%) patients with clinical indications
      for antibiotic treatment, 521 (11%) were inappropriately not prescribed
      antibiotics. Clinical officers were less likely than medical officers to
      inappropriately withhold antibiotics (aOR 0.54, 95% CI 0.29-0.98). CONCLUSION:
      Over 40% of the antibiotic treatment in malaria positive patients is prescribed
      despite a lack of documented clinical indication. In addition, over 10% of
      patients with malaria and a clinical indication for antibiotics do not receive
      them. These findings should inform facility-level trainings and interventions to
      optimize patient care and slow trends of rising antibiotic resistance.

PMID- 24587265
TI  - Quantitative proteomics approach to screening of potential diagnostic and
      therapeutic targets for laryngeal carcinoma.
AB  - To discover candidate biomarkers for diagnosis and detection of human laryngeal
      carcinoma and explore possible mechanisms of this cancer carcinogenesis, two
      dimensional strong cation-exchange/reversed-phase nano-scale liquid
      chromatography/mass spectrometry analysis was used to identify differentially
      expressed proteins between the laryngeal carcinoma tissue and the adjacent normal
      tissue. As a result, 281 proteins with significant difference in expression were
      identified, and four differential proteins, Profilin-1 (PFN1), Nucleolin (NCL),
      Cytosolic non-specific dipeptidase (CNDP2) and Mimecan (OGN) with different
      subcellular localization were selectively validated. Semiquantitative RT-PCR and
      Western blotting were performed to detect the expression of the four proteins
      employing a large collection of human laryngeal carcinoma tissues, and the
      results validated the differentially expressed proteins identified by the
      proteomics. Furthermore, we knocked down PFN1 in immortalized human laryngeal
      squamous cell line Hep-2 cells and then the proliferation and metastasis of these
      transfected cells were measured. The results showed that PFN1 silencing inhibited
      the proliferation and affected the migration ability of Hep-2 cells, providing
      some new insights into the pathogenesis of PFN1 in laryngeal carcinoma.
      Altogether, our present data first time show that PFN1, NCL, CNDP2 and OGN are
      novel potential biomarkers for diagnosis and therapeutic targets for laryngeal
      carcinoma, and PFN1 is involved in the metastasis of laryngeal carcinoma. 

PMID- 24587266
TI  - BMI, a performance parameter for speed improvement.
AB  - The purpose of this study is to investigate the association between
      anthropometric characteristics and performance in all track and field running
      events and assess Body Mass Index (BMI) as a relevant performance indicator. Data
      of mass, height, BMI and speed were collected for the top 100 international men
      athletes in track events from 100 m to marathon for the 1996-2011 seasons, and
      analyzed by decile of performance. Speed is significantly associated with mass (r
      = 0.71) and BMI (r = 0.71) in world-class runners and moderately with height (r =
      0.39). Athletes, on average were continuously lighter and smaller with distance
      increments. In track and field, speed continuously increases with BMI. In each
      event, performances are organized through physique gradients. " Lighter and
      smaller is better " in endurance events but " heavier and taller is better " for
      sprints. When performance increases, BMI variability progressively tightens, but
      it is always centered around a distance-specific optimum. Running speed is
      organized through biometric gradients, which both drives and are driven by
      performance optimization. The highest performance level is associated with
      narrower biometric intervals. Through BMI indicators, diversity is possible for
      sprints whereas for long distance events, there is a more restrictive aspect in
      terms of physique. BMI is a relevant indicator, which allows for a clear
      differentiation of athletes' capacities between each discipline and level of
      performance in the fields of human possibilities.

PMID- 24587267
TI  - Occlusal enamel complexity in middle miocene to holocene equids (Equidae:
      Perissodactyla) of North America.
AB  - Four groups of equids, "Anchitheriinae," Merychippine-grade Equinae,
      Hipparionini, and Equini, coexisted in the middle Miocene, but only the Equini
      remains after 16 Myr of evolution and extinction. Each group is distinct in its
      occlusal enamel pattern. These patterns have been compared qualitatively but
      rarely quantitatively. The processes influencing the evolution of these occlusal
      patterns have not been thoroughly investigated with respect to phylogeny, tooth
      position, and climate through geologic time. We investigated Occlusal Enamel
      Index, a quantitative method for the analysis of the complexity of occlusal
      patterns. We used analyses of variance and an analysis of co-variance to test
      whether equid teeth increase resistive cutting area for food processing during
      mastication, as expressed in occlusal enamel complexity, in response to increased
      abrasion in their diet. Results suggest that occlusal enamel complexity was
      influenced by climate, phylogeny, and tooth position through time. Occlusal
      enamel complexity in middle Miocene to Modern horses increased as the animals
      experienced increased tooth abrasion and a cooling climate. 

PMID- 24587268
TI  - Conditioned pain modulation and situational pain catastrophizing as preoperative
      predictors of pain following chest wall surgery: a prospective observational
      cohort study.
AB  - BACKGROUND: Variability in patients' postoperative pain experience and response
      to treatment challenges effective pain management. Variability in pain reflects
      individual differences in inhibitory pain modulation and psychological
      sensitivity, which in turn may be clinically relevant for the disposition to
      acquire pain. The aim of this study was to investigate the effects of conditioned
      pain modulation and situational pain catastrophizing on postoperative pain and
      pain persistency. METHODS: Preoperatively, 42 healthy males undergoing funnel
      chest surgery completed the Spielberger's State-Trait Anxiety Inventory and
      Beck's Depression Inventory before undergoing a sequential conditioned pain
      modulation paradigm. Subsequently, the Pain Catastrophizing Scale was introduced
      and patients were instructed to reference the conditioning pain while answering.
      Ratings of movement-evoked pain and consumption of morphine equivalents were
      obtained during postoperative days 2-5. Pain was reevaluated at six months
      postoperatively. RESULTS: Patients reporting persistent pain at six months follow
      up (n = 15) were not significantly different from pain-free patients (n = 16)
      concerning preoperative conditioned pain modulation response (Z = 1.0, P = 0.3)
      or level of catastrophizing (Z = 0.4, P = 1.0). In the acute postoperative phase,
      situational pain catastrophizing predicted movement-evoked pain, independently of
      anxiety and depression (beta = 1.0, P = 0.007) whereas conditioned pain
      modulation predicted morphine consumption (beta = -0.005, P = 0.001).
      CONCLUSIONS: Preoperative conditioned pain modulation and situational pain
      catastrophizing were not associated with the development of persistent
      postoperative pain following funnel chest repair. Secondary outcome analyses
      indicated that conditioned pain modulation predicted morphine consumption and
      situational pain catastrophizing predicted movement-evoked pain intensity in the
      acute postoperative phase. These findings may have important implications for
      developing strategies to treat or prevent acute postoperative pain in selected
      patients. Pain may be predicted and the malfunctioning pain inhibition mechanism
      as tested with CPM may be treated with suitable drugs augmenting descending
      inhibition.

PMID- 24587269
TI  - Pronounced fixation, strong population differentiation and complex population
      history in the Canary Islands blue tit subspecies complex.
AB  - Evolutionary molecular studies of island radiations may lead to insights in the
      role of vicariance, founder events, population size and drift in the processes of
      population differentiation. We evaluate the degree of population genetic
      differentiation and fixation of the Canary Islands blue tit subspecies complex
      using microsatellite markers and aim to get insights in the population history
      using coalescence based methods. The Canary Island populations were strongly
      genetically differentiated and had reduced diversity with pronounced fixation
      including many private alleles. In population structure models, the relationship
      between the central island populations (La Gomera, Tenerife and Gran Canaria) and
      El Hierro was difficult to disentangle whereas the two European populations
      showed consistent clustering, the two eastern islands (Fuerteventura and
      Lanzarote) and Morocco weak clustering, and La Palma a consistent unique lineage.
      Coalescence based models suggested that the European mainland forms an outgroup
      to the Afrocanarian population, a split between the western island group (La
      Palma and El Hierro) and the central island group, and recent splits between the
      three central islands, and between the two eastern islands and Morocco,
      respectively. It is clear that strong genetic drift and low level of concurrent
      gene flow among populations have shaped complex allelic patterns of fixation and
      skewed frequencies over the archipelago. However, understanding the population
      history remains challenging; in particular, the pattern of extreme divergence
      with low genetic diversity and yet unique genetic material in the Canary Island
      system requires an explanation. A potential scenario is population contractions
      of a historically large and genetically variable Afrocanarian population, with
      vicariance and drift following in the wake. The suggestion from sequence-based
      analyses of a Pleistocene extinction of a substantial part of North Africa and a
      Pleistocene/Holocene eastward re-colonisation of western North Africa from the
      Canaries remains possible. 

PMID- 24587270
TI  - Crosslinking-induced endocytosis of acetylcholine receptors by quantum dots.
AB  - In a majority of patients with myasthenia gravis (MG), anti-acetylcholine
      receptor (AChR) antibodies target postsynaptic AChR clusters and thus compromise
      the membrane integrity of neuromuscular junctions (NMJs) and lead to muscle
      weakness. Antibody-induced endocytosis of AChRs in the postsynaptic membrane
      represents the initial step in the pathogenesis of MG; however, the molecular
      mechanisms underlying AChR endocytosis remain largely unknown. Here, we developed
      an approach to mimic the pathogenic antibodies for inducing the crosslinking and
      internalization of AChRs from the postsynaptic membrane. Using biotin-alpha
      bungarotoxin and quantum dot (QD)-streptavidin, cell-surface and internalized
      AChRs could be readily distinguished by comparing the size, fluorescence
      intensity, trajectory, and subcellular localization of the QD signals. QD-induced
      AChR endocytosis was mediated by clathrin-dependent and caveolin-independent
      mechanisms, and the trafficking of internalized AChRs in the early endosomes
      required the integrity of microtubule structures. Furthermore, activation of the
      agrin/MuSK (muscle-specific kinase) signaling pathway strongly suppressed QD
      induced internalization of AChRs. Lastly, QD-induced AChR crosslinking
      potentiated the dispersal of aneural AChR clusters upon synaptic induction. Taken
      together, our results identify a novel approach to study the mechanisms of AChR
      trafficking upon receptor crosslinking and endocytosis, and demonstrate that
      agrin-MuSK signaling pathways protect against crosslinking-induced endocytosis of
      AChRs. 

PMID- 24587271
TI  - Evaluation of silicon nitride as a substrate for culture of PC12 cells: an
      interfacial model for functional studies in neurons.
AB  - Silicon nitride is a biocompatible material that is currently used as an
      interfacial surface between cells and large-scale integration devices
      incorporating ion-sensitive field-effect transistor technology. Here, we
      investigated whether a poly-L-lysine coated silicon nitride surface is suitable
      for the culture of PC12 cells, which are widely used as a model for neural
      differentiation, and we characterized their interaction based on cell behavior
      when seeded on the tested material. The coated surface was first examined in
      terms of wettability and topography using contact angle measurements and atomic
      force microscopy and then, conditioned silicon nitride surface was used as the
      substrate for the study of PC12 cell culture properties. We found that coating
      silicon nitride with poly-L-lysine increased surface hydrophilicity and that
      exposing this coated surface to an extracellular aqueous environment gradually
      decreased its roughness. When PC12 cells were cultured on a coated silicon
      nitride surface, adhesion and spreading were facilitated, and the cells showed
      enhanced morphological differentiation compared to those cultured on a plastic
      culture dish. A bromodeoxyuridine assay demonstrated that, on the coated silicon
      nitride surface, higher proportions of cells left the cell cycle, remained in a
      quiescent state and had longer survival times. Therefore, our study of the
      interaction of the silicon nitride surface with PC12 cells provides important
      information for the production of devices that need to have optimal cell culture
      supporting properties in order to be used in the study of neuronal functions. 

PMID- 24587272
TI  - Functional abstraction as a method to discover knowledge in gene ontologies.
AB  - Computational analyses of functions of gene sets obtained in microarray analyses
      or by topical database searches are increasingly important in biology. To
      understand their functions, the sets are usually mapped to Gene Ontology
      knowledge bases by means of over-representation analysis (ORA). Its result
      represents the specific knowledge of the functionality of the gene set. However,
      the specific ontology typically consists of many terms and relationships,
      hindering the understanding of the 'main story'. We developed a methodology to
      identify a comprehensibly small number of GO terms as "headlines" of the specific
      ontology allowing to understand all central aspects of the roles of the involved
      genes. The Functional Abstraction method finds a set of headlines that is
      specific enough to cover all details of a specific ontology and is abstract
      enough for human comprehension. This method exceeds the classical approaches at
      ORA abstraction and by focusing on information rather than decorrelation of GO
      terms, it directly targets human comprehension. Functional abstraction provides,
      with a maximum of certainty, information value, coverage and conciseness, a
      representation of the biological functions in a gene set plays a role. This is
      the necessary means to interpret complex Gene Ontology results thus strengthening
      the role of functional genomics in biomarker and drug discovery. 

PMID- 24587273
TI  - Insulin production hampered by intermittent hypoxia via impaired zinc
      homeostasis.
AB  - Without zinc, pancreatic beta cells cannot either assemble insulin molecules or
      precipitate insulin crystals; thus, a lack of zinc concentration in the beta
      cells would result in a decreased insulin production. ZIP8 is one of the zinc
      uptake transporters involved in zinc influx into the cytosol of beta cells. Thus,
      if ZIP8 is down-regulated, a decreased insulin production would result. We
      assumed that intermittent hypoxic exposure to the beta cells may result in a
      decreased production of insulin due to a lack of zinc. To test this hypothesis we
      harvested pancreatic islets from the rats conditioned under intermittent hypoxia
      (IH) (fluctuating between 20.5% and 10% every 4 min for 1 h) and compared the
      results with those from control animals and islets. We also compared their
      insulin and glucose homeostasis using glucose tolerance tests (GTT) after 3
      weeks. GTT results show a significant delay (P<0.05) in recovery of the blood
      glucose level in IH treated pups. ZIP8 expression in the beta cell membrane was
      down-regulated. The zinc concentration in the cell as well as insulin production
      was significantly decreased in the islets harvested from IH animals. However,
      mRNA for insulin and C-peptide/insulin protein levels in the total cell lysates
      remained the same as those of controls. When we treated the beta cells using
      siRNA mediated ZIP8, we observed the commensurate results from the IH-treated
      islets. We conclude that a transient IH exposure could knockdown ZIP8
      transporters at mRNA as well as protein levels in the beta cells, which would
      decrease the level of blood insulin. However, the transcriptional activity of
      insulin remains the same. We conclude that the precipitation process of insulin
      crystal may be disturbed by a lack of zinc in the cytosol that is modulated by
      mainly ZIP8 after IH exposure. 

PMID- 24587274
TI  - Physical activity and constipation in Hong Kong adolescents.
AB  - OBJECTIVE: To examine the association of constipation with exercise, non-exercise
      physical activity, and sedentary behaviours in Hong Kong adolescents. METHODS: In
      2006-2007, 42 secondary schools were randomly selected to participate in the Hong
      Kong Student Obesity Surveillance (HKSOS) project. A total of 33692 Form 1-7
      students (44.9% boys; mean age 14.8, SD 1.9 years) completed an anonymous
      questionnaire on lifestyle behaviours. Constipation was defined as a frequency of
      evacuation of less than once every two days. Exercise (moderate-to-vigorous
      levels) and non-exercise physical activity (NEPA) were each considered
      insufficient when less than 1 hour per day, and sedentary behaviours were
      considered excessive when over 4 hours per day. Logistic regression was used to
      calculate adjusted odds ratio (AOR) for constipation in relation to exercise,
      NEPA, and sedentary behaviours, adjusting for potential confounders. RESULTS:
      Constipation was identified in 15.6% (95% CI 15.2% - 16.0%) of adolescents
      overall, 14.0% in those with sufficient exercise and 19.6% in those without.
      Constipation was associated with insufficient exercise (AOR 1.26, 95% CI 1.16 -
      1.36), insufficient NEPA 1.21 (1.10 - 1.33) and excessive sedentary behaviours
      (1.25, 1.17 - 1.34). Compared with having none of the above 3 inactive
      behaviours, increasing AORs of constipation were observed for having 1 (AOR
      1.23), 2 (AOR 1.57) and 3 (AOR 1.88) inactive behaviours (p for trend <0.001).
      CONCLUSIONS: Constipation was associated with insufficient physical activity and
      excessive sedentary behaviours among Chinese adolescents with a dose-response
      relation. If the association is causal, constipation could be prevented by
      promotion of physical activity.

PMID- 24587275
TI  - Seroprevalence of hepatitis B virus among adults at high risk for HIV
      transmission two decades after implementation of nationwide hepatitis B virus
      vaccination program in Taiwan.
AB  - BACKGROUND: Seroprevalence of hepatitis B virus (HBV) after implementation of
      universal neonatal HBV vaccination and catch-up vaccination programs remains
      rarely investigated among the adults who were born in the vaccination era (in or
      after 1986) and engaged in high-risk sexual behaviors. MATERIALS AND METHODS:
      Between 2006 and 2012, we determined HBV surface antigen ([HBsAg), anti-HBs, and
      HBV core antibody (anti-HBc), hepatitis C virus antibody (anti-HCV) and rapid
      plasma reagin titers among HIV-infected men who have sex with men (MSM) born
      during 1984-1985 (Group I: 244 persons) and those born in or after 1986 (Group
      II: 523), and HIV-uninfected MSM (Group III: 377) and heterosexuals (Group IV:
      217) born in or after 1986. Prevalence and incidence of HBV infection were
      estimated and multivariate analysis was performed to identify factors associated
      with HBsAg positivity. RESULTS: Compared with Group I, Groups II-IV had a
      significantly lower prevalence of HBsAg positivity (7.8% vs 3.7%, 2.4%, and 3.2%,
      respectively); and the prevalence of anti-HBc positivity was also lower for
      Groups III and IV (30.3% vs. 19.6%, and 18.0%, respectively), but no difference
      was observed between Groups I and II (30.3% vs. 26.3%). In multivariate analysis,
      HBsAg positivity was significantly associated with syphilis (adjusted odds ratio,
      2.990; 95% confidence interval, 1.502-5.953) and anti-HCV positivity (adjusted
      odds ratio, 3.402; 95% confidence interval, 1.091-10.614). In subjects of Group
      II with all-negative HBV markers at baseline, the incidence rate of HBsAg
      seroconversion was 0.486 episodes per 100 person-years; and for those who
      received combination antiretroviral therapy containing lamivudine and/or
      tenofovir, none developed HBsAg seroconversion during the follow-up. CONCLUSIONS:
      Among the adults who were born in or after 1986 and engaged in high-risk sexual
      behaviors in Taiwan, neonatal HBV vaccination and catch-up vaccination programs
      conferred long-term protection against HBsAg seroconversion and HBsAg positivity
      was associated with syphilis and anti-HCV positivity.

PMID- 24587277
TI  - Endobiotic rugosan symbionts in stromatoporoids from the Sheinwoodian (Silurian)
      of Baltica.
AB  - A paleoecological study of stromatoporoid endobionts was carried out to discern
      the relationships between symbiotic rugosans and their stromatoporoid hosts. The
      earliest endobiotic rugosan symbiont Palaeophyllum sp. in Baltica has only been
      found in the stromatoporoid Ecclimadictyon astrolaxum from Saaremaa, Estonia. The
      rugosans are vertically oriented inside the stromatoporoid skeleton. Numerous
      rugosans have their corallites open at the upper, external surface of
      stromatoporoids, but many are completely embedded within the stromatoporoids.
      Stromatoporoid hosts were presumably beneficial for rugosans as elevated
      substrates on a sea floor that offered a higher tier for feeding. Relative
      substrate stability in the hydrodynamically active shallow waters may have also
      been beneficial for the rugosans. 

PMID- 24587276
TI  - Enhanced response of T cells from murine gammaherpesvirus 68-infected mice
      lacking the suppressor of T cell receptor signaling molecules Sts-1 and Sts-2.
AB  - The human gammaherpesviruses establish life-long infections that are associated
      with the development of lymphomas and neoplasms, especially in immunocompromised
      individuals. T cells play a crucial role in the control of gammaherpesvirus
      infection through multiple functions, including the direct killing of infected
      cells, production of cytokines such as interferon-gamma (IFN-gamma), and
      costimulation of B cells. Impaired T cell function in mice infected with murine
      gammaherpesvirus 68 (MHV68) leads to increased reactivation and pathologies,
      including a higher incidence of lymphoid hyperplasia. Here we report that the
      absence of Suppressor of TCR signaling -1 and -2 (Sts-1(-/-)/2(-/-)) during MHV68
      infection leads to the generation of T cells with significantly heightened
      responses. Transient differences in the T and B cell response of infected Sts-1(
      /-)/2(-/-) (Sts dKO) mice were also observed when compared to WT mice. However,
      these alterations in the immune response and the overall absence of Sts-1 and Sts
      2 did not impact viral pathogenesis or lead to pathology. Acute lytic replication
      in the lungs, establishment of latency in the spleen and reactivation from
      latency in the spleen in the Sts dKO mice were comparable to WT mice. Our studies
      indicate that Sts-1 and Sts-2 are not required for the immune control of MHV68 in
      a normal course of gammaherpesvirus infection, but suggest that interference with
      negative regulators of T cell responses might be further explored as a safe and
      efficacious strategy to improve adoptive T cell therapy. 

PMID- 24587278
TI  - Revisiting Russell's viper (Daboia russelii) bite in Sri Lanka: is abdominal pain
      an early feature of systemic envenoming?
AB  - The Russell's viper (Daboia russelii) is responsible for 30-40% of all snakebites
      and the most number of life-threatening bites of any snake in Sri Lanka. The
      clinical profile of Russell's viper bite includes local swelling, coagulopathy,
      renal dysfunction and neuromuscular paralysis, based on which the syndromic
      diagnostic tools have been developed. The currently available Indian polyvalent
      antivenom is not very effective in treating Russell's viper bite patients in Sri
      Lanka and the decision regarding antivenom therapy is primarily driven by
      clinical and laboratory evidence of envenoming. The non-availability of early
      predictors of Russell's viper systemic envenoming is responsible for considerable
      delay in commencing antivenom. The objective of this study is to evaluate
      abdominal pain as an early feature of systemic envenoming following Russell's
      viper bites. We evaluated the clinical profile of Russell's viper bite patients
      admitted to a tertiary care centre in Sri Lanka. Fifty-five patients were proven
      Russell's viper bite victims who produced the biting snake, while one hundred and
      fifty-four were suspected to have been bitten by the same snake species.
      Coagulopathy (159, 76.1%), renal dysfunction (39, 18.7%), neuromuscular paralysis
      (146, 69.9%) and local envenoming (192, 91.9%) were seen in the victims, ranging
      from mono-systemic involvement to various combinations. Abdominal pain was
      present in 79.5% of these patients, appearing 5 minutes to 4 hours after the
      bite. The severity of the abdominal pain, assessed using a scoring system,
      correlated well with the severity of the coagulopathy (p<0.001) and the
      neurotoxicity (p<0.001). Its diagnostic validity to predict systemic envenoming
      is - Sensitivity 81.6%, Specificity 82.4%, Positive predictive value 91.2%. Thus,
      abdominal pain is an early clinical feature of systemic Russell's viper bite
      envenoming in Sri Lanka. However, it is best to judge abdominal pain together
      with other clinical manifestations on decision making. 

PMID- 24587279
TI  - Association of lower extremity arterial calcification with amputation and
      mortality in patients with symptomatic peripheral artery disease.
AB  - OBJECTIVE: The clinical implication of the coronary artery calcium score (CS) is
      well demonstrated. However, little is known about the association between lower
      extremity arterial calcification and clinical outcomes. METHODS AND RESULTS:
      Eighty-two patients with symptomatic peripheral artery disease (age 61.0+/-12.4
      years) were followed for 21+/-11 months. CSs, ranging from the common iliac
      artery bifurcation to the ankle area, were analyzed through noncontrast
      multidetector computed tomography images retrospectively. The primary endpoints
      of this study were amputation and mortality. Old age, diabetes, hyperlipidemia,
      and end-stage renal disease were associated with higher CSs. Patients with more
      advanced Fontaine stages also tended to have significantly higher CSs (p = 0.03).
      During the follow-up period (21+/-11 months), 29 (35%) patients underwent
      amputation, and 24 (29%) patients died. Among the patients who underwent
      amputation, there were no significant differences in CSs between the amputated
      legs and the non-amputated legs. In the Cox proportional hazard model with CS
      divided into quartiles, patients with CS in the highest quartile had a 2.88-fold
      (95% confidence interval [CI] 1.18-12.72, p = 0.03) and a 5.16-fold (95% CI 1.13
      21.61, p = 0.04) higher risk for amputation and all-cause mortality,
      respectively, than those with CS in the lowest quartile. These predictive effects
      remained after conventional risk factor adjustment. CONCLUSION: Lower extremity
      arterial CSs are associated with disease severity and outcomes, including
      amputation and all-cause mortality, in patients with symptomatic peripheral
      artery disease. However, the independent predictive value needs further
      investigation in large scale, prospective studies.

PMID- 24587280
TI  - Trehalose reverses cell malfunction in fibroblasts from normal and Huntington's
      disease patients caused by proteosome inhibition.
AB  - Huntington's disease (HD) is a neurodegenerative disorder characterized by
      progressive motor, cognitive and psychiatric deficits, associated with
      predominant loss of striatal neurons and is caused by polyglutamine expansion in
      the huntingtin protein. Mutant huntingtin protein and its fragments are resistant
      to protein degradation and produce a blockade of the ubiquitin proteasome system
      (UPS). In HD models, the proteasome inhibitor epoxomicin aggravates protein
      accumulation and the inductor of autophagy, trehalose, diminishes it. We have
      investigated the effects of epoxomicin and trehalose in skin fibroblasts of
      control and HD patients. Untreated HD fibroblasts have increased the levels of
      ubiquitinized proteins and higher levels of reactive oxygen species (ROS),
      huntingtin and the autophagy marker LAMP2A. Baseline replication rates were
      higher in HD than in controls fibroblasts but that was reverted after 12
      passages. Epoxomicin increases the activated caspase-3, HSP70, huntingtin,
      ubiquitinated proteins and ROS levels in both HD and controls. Treatment with
      trehalose counteracts the increase in ROS, ubiquitinated proteins, huntingtin and
      activated caspase-3 levels induced by epoxomicin, and also increases the LC3
      levels more in HD fibroblast than controls. These results suggest that trehalose
      could revert protein processing abnormalities in patients with Huntington's
      Disease. 

PMID- 24587281
TI  - Social housing improves dairy calves' performance in two cognitive tests.
AB  - Early social housing is known to benefit cognitive development in laboratory
      animals. Pre-weaned dairy calves are typically separated from their dam
      immediately after birth and housed alone, but no work to date has addressed the
      effect of individual housing on cognitive performance of these animals. The aim
      of this study was to determine the effects of individual versus social housing on
      two measures of cognitive performance: reversal learning and novel object
      recognition. Holstein calves were either housed individually in a standard calf
      pen (n = 8) or kept in pairs using a double pen (n = 10). Calves were tested
      twice daily in a Y-maze starting at 3 weeks of age. Calves were initially trained
      to discriminate two colours (black and white) until they reached a learning
      criterion of 80% correct over three consecutive sessions. Training stimuli were
      then reversed (i.e. the previously rewarded colour was now unrewarded, and vice
      versa). Calves from the two treatments showed similar rates of learning in the
      initial discrimination task, but the individually housed calves showed poorer
      performance in the reversal task. At 7 weeks of age, calves were tested for their
      response to a novel object in eight tests over a two-day period. Pair-housed
      calves showed declining exploration with repeated testing but individually reared
      calves did not. The results of these experiments provide the first direct
      evidence that individual housing impairs cognitive performance in dairy calves. 

PMID- 24587282
TI  - eEF1A is an S-RNase binding factor in self-incompatible Solanum chacoense.
AB  - Self-incompatibility (SI) is a genetic mechanism that allows flowering plants to
      identify and block fertilization by self-pollen. In the Solanaceae, SI is
      controlled by a multiallelic S-locus encoding both S-RNases and F-box proteins as
      female and male determinants, respectively. S-RNase activity is essential for
      pollen rejection, and a minimum threshold value of S-RNases in the style is also
      required. Here we present biochemical evidence that eEF1A is a novel S-RNase
      binding partner in vitro. We further show that the normal actin binding activity
      of eEF1A is enhanced by the presence of S-RNase. Lastly, we find that there is a
      co-localization of S-RNase and actin in the incompatible pollen tubes in
      structures reminiscent of the actin bundles formed by eEF1A. We propose that
      increased binding of eEF1A to actin in the presence of S-RNase could help explain
      the disruption of the actin cytoskeleton observed during SI reactions. 

PMID- 24587283
TI  - Remating and sperm competition in replicate populations of Drosophila
      melanogaster adapted to alternative environments.
AB  - The prevalence of sexual conflict in nature, as well as the supposedly arbitrary
      direction of the resulting coevolutionary trajectories, suggests that it may be
      an important driver of phenotypic divergence even in a constant environment.
      However, natural selection has long been central to the operation of sexual
      conflict within populations and may therefore constrain or otherwise direct
      divergence among populations. Ecological context may therefore matter with
      respect to the diversification of traits involved in sexual conflict, and if
      natural selection is sufficiently strong, such traits may evolve in correlation
      with environment, generating a pattern of ecologically-dependent parallel
      evolution. In this study we assess among-population divergence both within and
      between environments for several traits involved in sexual conflict. Using eight
      replicate populations of Drosophila melanogaster from a long-term evolution
      experiment, we measured remating rates and subsequent offspring production of
      females when housed with two separate males in sequence. We found no evidence of
      any variation in male reproductive traits (offense or defense). However, the
      propensity of females to remate diverged significantly among the eight
      populations with no evidence of any environmental effect, consistent with sexual
      conflict promoting diversification even in the absence of ecological differences.
      On the other hand, females adapted to one environment (ethanol) tended to produce
      a higher proportion of offspring sired by their first mate as compared to those
      adapted to the other (cadmium) environment, suggesting ecologically-based
      divergence of this conflict phenotype. Because we find evidence for both
      stochastic population divergence operating outside of an ecological context and
      environment-dependent divergence of traits under sexual conflict, the interaction
      of these two processes is an important topic for future work. 

PMID- 24587284
TI  - Development of a strain-specific real-time PCR assay for enumeration of a
      probiotic Lactobacillus reuteri in chicken feed and intestine.
AB  - A strain-specific real-time PCR assay was developed for quantification of a
      probiotic Lactobacillus reuteri (DSM 16350) in poultry feed and intestine. The
      specific primers were designed based on a genomic sequence of the strain derived
      from suppression subtractive hybridization with the type strain L. reuteri DSM
      20016. Specificity was tested using a set of non-target strains from several
      sources. Applicability of the real-time PCR assay was evaluated in a controlled
      broiler feeding trial by using standard curves specific for feed and intestinal
      matrices. The amount of the probiotic L. reuteri was determined in feed from
      three feeding phases and in intestinal samples of the jejunum, ileum, and caecum
      of three, 14, and 39 day old birds. L. reuteri DSM 16350 cells were enumerated in
      all feeds supplemented with the probiotic close to the inclusion rate of 7.0 *
      10(3) cfu/g, however, were not detected in L. reuteri DSM 16350 free feed. In
      three day old birds L. reuteri DSM 16350 was only detected in intestinal samples
      from probiotic fed animals ranging from 8.2 +/- 7.8 * 10(5) cfu/g in the jejunum,
      1.0 +/- 1.1*10(7) cfu/g in the ileum, and 2.5 +/- 5.7 * 10(5) cfu/g in the
      caecum. Similar results were obtained for intestinal samples of older birds (14
      and 39 days). With increasing age of the animals the amount of L. reuteri signals
      in the control animals, however, also increased, indicating the appearance of
      highly similar bacterial genomes in the gut microbiota. The L. reuteri DSM 16350
      qPCR assay could be used in future for feeding trials to assure the accurate
      inclusion of the supplement to the feed and to monitor it's uptake into the GIT
      of young chicken.

PMID- 24587285
TI  - Differential regulation of hepatic transcription factors in the Wistar rat
      offspring born to dams fed folic acid, vitamin B12 deficient diets and
      supplemented with omega-3 fatty acids.
AB  - Nutritional status of the mother is known to influence various metabolic
      adaptations required for optimal fetal development. These may be mediated by
      transcription factors like peroxisome proliferator activated receptors (PPARs),
      which are activated by long chain polyunsaturated fatty acids. The objective of
      the current study was to examine the expression of different hepatic
      transcription factors and the levels of global methylation in the liver of the
      offspring born to dams fed micronutrient deficient (folic acid and vitamin B12)
      diets and supplemented with omega-3 fatty acids. Female rats were divided into
      five groups (n = 8/group) as follows; control, folic acid deficient (FD), vitamin
      B12 deficient (BD) and omega-3 fatty acid supplemented groups (FDO and BDO).
      Diets were given starting from pre-conception and continued throughout pregnancy
      and lactation. Pups were dissected at the end of lactation. Liver tissues were
      removed; snap frozen and stored at -80 degrees C. Maternal micronutrients
      deficiency resulted in lower (p<0.05) levels of pup liver docosahexaenoic acid
      (DHA) and arachidonic acid (ARA) as compared to the control group. Pup liver
      PPARalpha and PPARgamma expression was lower (p<0.05) in the BD group although
      there were no differences in the expression of SREBP-1c, LXRalpha and RXRalpha
      expression. Omega-3 fatty acids supplementation to this group normalized (p<0.05)
      levels of both PPARalpha and PPARgamma but reduced (p<0.05) SREBP-1c, LXRalpha
      and RXRalpha expression. There was no change in any of the transcription factors
      in the pup liver in the FD group. Omega-3 fatty acids supplementation to this
      group reduced (p<0.05) PPARalpha, SREBP-1c and RXRalpha expression. Pup liver
      global methylation levels were higher (p<0.01) in both the micronutrients
      deficient groups and could be normalized (p<0.05) by omega-3 fatty acid
      supplementation. Our novel findings suggest a role for omega-3 fatty acids in the
      one carbon cycle in influencing the hepatic expression of transcription factors
      in the offspring.

PMID- 24587286
TI  - The transcervical approach for parapharyngeal space pleomorphic adenomas:
      indications and technique.
AB  - BACKGROUND: Head and Neck Parapharyngeal space tumors are rare. Pleomorphic
      Adenomas are the most common Parapharyngeal space tumors. The purpose of this
      study was to define preoperative criteria for enabling full extirpation of
      parapharyngeal space pleomorphic adenomas via the transcervical approach while
      minimizing functional and cosmetic morbidity. METHODS: The surgical records and
      medical charts of 19 females and 10 males with parapharyngeal space pleomorphic
      adenomas operated between 1993 and 2012 were reviewed. RESULTS: Fifteen patients
      were operated by a simple transcervical approach, 13 by a transparotid
      transcervical approach, and one by a transmandibular transcervical approach.
      Complications included facial nerve paralysis, infection, hemorrhage and first
      bite syndrome. There were three recurrences, but neither recurrence nor
      complications were associated with the type of surgical approach. CONCLUSION: A
      simple transcervical approach is preferred for parapharyngeal space pleomorphic
      adenomas with narrow attachments to the deep lobe of the parotid gland and for
      pleomorphic adenomas originating in a minor salivary gland within the
      parapharyngeal space.

PMID- 24587287
TI  - Vascular injury post stent implantation: different gene expression modulation in
      human umbilical vein endothelial cells (HUVECs) model.
AB  - To explore whether stent procedure may influence transcriptional response of
      endothelium, we applied different physical (flow changes) and/or mechanical
      (stent application) stimuli to human endothelial cells in a laminar flow
      bioreactor (LFB) system. Gene expression analysis was then evaluated in each
      experimental condition. Human umbilical vein endothelial cells (HUVECs) were
      submitted to low and physiological (1 and 10 dyne/cm(2)) shear stress in absence
      (AS) or presence (PS) of stent positioning in a LFB system for 24 h. Different
      expressed genes, coming from Affymetrix results, were identified based on one-way
      ANOVA analysis with p values <0.01 and a fold changed >3 in modulus. Low shear
      stress was compared with physiological one in AS and PS conditions. Two major
      groups include 32 probes commonly expressed in both 1AS versus 10AS and 1PS
      versus 10PS comparison, and 115 probes consisting of 83 in addition to the
      previous 32, expressed only in 1PS versus 10PS comparison. Genes related to
      cytoskeleton, extracellular matrix, and cholesterol transport/metabolism are
      differently regulated in 1PS versus 10PS condition. Inflammatory and apoptotic
      mediators seems to be, instead, closely modulated by changes in flow (1 versus
      10), independently of stent application. Low shear stress together with stent
      procedure are the experimental conditions that mainly modulate the highest number
      of genes in our human endothelial model. Those genes belong to pathways
      specifically involved in the endothelial dysfunction. 

PMID- 24587288
TI  - B chromosomes of Aegilops speltoides are enriched in organelle genome-derived
      sequences.
AB  - B chromosomes (Bs) are dispensable components of the genome exhibiting non
      Mendelian inheritance. Chromosome counts and flow cytometric analysis of the
      grass species Aegilops speltoides revealed a tissue-type specific distribution of
      the roughly 570 Mbp large B chromosomes. To address the question whether
      organelle-to-nucleus DNA transfer is a mechanism that drives the evolution of Bs,
      in situ hybridization was performed with labelled organellar DNA. The observed B
      specific accumulation of chloroplast- and mitochondria-derived sequences suggests
      a reduced selection against the insertion of organellar DNA in supernumerary
      chromosomes. The distribution of B-localised organellar-derived sequences and
      other sequences differs between genotypes of different geographical origins. 

PMID- 24587289
TI  - Uncovering the rare variants of DLC1 isoform 1 and their functional effects in a
      Chinese sporadic congenital heart disease cohort.
AB  - Congenital heart disease (CHD) is the most common birth defect affecting the
      structure and function of fetal hearts. Despite decades of extensive studies, the
      genetic mechanism of sporadic CHD remains obscure. Deleted in liver cancer 1
      (DLC1) gene, encoding a GTPase-activating protein, is highly expressed in heart
      and essential for heart development according to the knowledge of Dlc1-deficient
      mice. To determine whether DLC1 is a susceptibility gene for sporadic CHD, we
      sequenced the coding region of DLC1 isoform 1 in 151 sporadic CHD patients and
      identified 13 non-synonymous rare variants (including 6 private variants) in the
      case cohort. Importantly, these rare variants (8/13) were enriched in the N
      terminal region of the DLC1 isoform 1 protein. Seven of eight amino acids at the
      N-terminal variant positions were conserved among the primates. Among the 9 rare
      variants that were predicted as "damaging", five were located at the N-terminal
      region. Ensuing in vitro functional assays showed that three private variants
      (Met360Lys, Glu418Lys and Asp554Val) impaired the ability of DLC1 to inhibit cell
      migration or altered the subcellular location of the protein compared to wild
      type DLC1 isoform 1. These data suggest that DLC1 might act as a CHD-associated
      gene in addition to its role as a tumor suppressor in cancer. 

PMID- 24587290
TI  - Evaluating group housing strategies for the ex-situ conservation of harlequin
      frogs (Atelopus spp.) using behavioral and physiological indicators.
AB  - We have established ex situ assurance colonies of two endangered Panamanian
      harlequin frogs, Atelopus certus and Atelopus glyphus, but observed that males
      fought with each other when housed as a group. Housing frogs individually
      eliminated this problem, but created space constraints. To evaluate the potential
      stress effects from aggressive interactions when grouping frogs, we housed male
      frogs in replicated groups of one, two, and eight. We measured aggressive
      behavioral interactions and fecal glucocorticoid metabolite (GC) concentrations
      as indicators of stress in each tank. In both small and large groups, frogs
      initially interacted aggressively, but aggressive interactions and fecal GCs
      declined significantly after the first 2 weeks of being housed together, reaching
      the lowest levels by week 4. We conclude that aggressive interactions in same-sex
      groups of captive Atelopus may initially cause stress, but the frogs become
      habituated within a few weeks and they can safely be housed in same-sex groups
      for longer periods of time. 

PMID- 24587291
TI  - Independent expansion of zincin metalloproteinases in Onygenales fungi may be
      associated with their pathogenicity.
AB  - To get a comprehensive view of fungal M35 family (deuterolysin) and M36 family
      (fungalysin) genes, we conducted genome-wide investigations and phylogenetic
      analyses of genes in these two families from 50 sequenced Ascomycota fungi with
      different life styles. Large variations in the number of M35 family and M36
      family genes were found among different fungal genomes, indicating that these two
      gene families have been highly dynamic through fungal evolution. Moreover, we
      found obvious expansions of Meps in two families of Onygenales: Onygenaceae and
      Arthodermataceae, whereas species in family Ajellomycetace did not show expansion
      of these genes. The strikingly different gene duplication and loss patterns in
      Onygenales may be associated with the different pathogenicity of these species.
      Interestingly, likelihood ratio tests (LRT) of both M35 family and M36 family
      genes suggested that several branches leading to the duplicated genes in
      dermatophytic and Coccidioides fungi had signatures of positive selection,
      indicating that the duplicated Mep genes have likely diverged functionally to
      play important roles during the evolution of pathogenicity of dermatophytic and
      Coccidioides fungi. The potentially positively selected residues discovered by
      our analysis may have contributed to the development of new physiological
      functions of the duplicated Mep genes in dermatophytic fungi and Coccidioides
      species. Our study adds to the current knowledge of the evolution of Meps in
      fungi and also establishes a theoretical foundation for future experimental
      investigations. 

PMID- 24587293
TI  - Sequence depth, not PCR replication, improves ecological inference from next
      generation DNA sequencing.
AB  - Recent advances in molecular approaches and DNA sequencing have greatly
      progressed the field of ecology and allowed for the study of complex communities
      in unprecedented detail. Next generation sequencing (NGS) can reveal powerful
      insights into the diversity, composition, and dynamics of cryptic organisms, but
      results may be sensitive to a number of technical factors, including molecular
      practices used to generate amplicons, sequencing technology, and data processing.
      Despite the popularity of some techniques over others, explicit tests of the
      relative benefits they convey in molecular ecology studies remain scarce. Here we
      tested the effects of PCR replication, sequencing depth, and sequencing platform
      on ecological inference drawn from environmental samples of soil fungi. We
      sequenced replicates of three soil samples taken from pine biomes in North
      America represented by pools of either one, two, four, eight, or sixteen PCR
      replicates with both 454 pyrosequencing and Illumina MiSeq. Increasing the number
      of pooled PCR replicates had no detectable effect on measures of alpha- and beta
      diversity. Pseudo-beta-diversity - which we define as dissimilarity between re
      sequenced replicates of the same sample - decreased markedly with increasing
      sampling depth. The total richness recovered with Illumina was significantly
      higher than with 454, but measures of alpha- and beta-diversity between a larger
      set of fungal samples sequenced on both platforms were highly correlated. Our
      results suggest that molecular ecology studies will benefit more from investing
      in robust sequencing technologies than from replicating PCRs. This study also
      demonstrates the potential for continuous integration of older datasets with
      newer technology. 

PMID- 24587292
TI  - Polar localization of PhoN2, a periplasmic virulence-associated factor of
      Shigella flexneri, is required for proper IcsA exposition at the old bacterial
      pole.
AB  - Proper protein localization is critical for bacterial virulence. PhoN2 is a
      virulence-associated ATP-diphosphohydrolase (apyrase) involved in IcsA-mediated
      actin-based motility of S. flexneri. Herein, by analyzing a DeltaphoN2 mutant of
      the S. flexneri strain M90T and by generating phoN2::HA fusions, we show that
      PhoN2, is a periplasmic protein that strictly localizes at the bacterial poles,
      with a strong preference for the old pole, the pole where IcsA is exposed, and
      that it is required for proper IcsA exposition. PhoN2-HA was found to be polarly
      localized both when phoN2::HA was ectopically expressed in a Escherichia coli K
      12 strain and in a S. flexneri virulence plasmid-cured mutant, indicating a
      conserved mechanism of PhoN2 polar delivery across species and that neither IcsA
      nor the expression of other virulence-plasmid encoded genes are involved in this
      process. To assess whether PhoN2 and IcsA may interact, two-hybrid and cross
      linking experiments were performed. While no evidence was found of a PhoN2-IcsA
      interaction, unexpectedly the outer membrane protein A (OmpA) was shown to bind
      PhoN2-HA through its periplasmic-exposed C-terminal domain. Therefore, to
      identify PhoN2 domains involved in its periplasmic polar delivery as well as in
      the interaction with OmpA, a deletion and a set of specific amino acid
      substitutions were generated. Analysis of these mutants indicated that neither
      the (183)PAPAP(187) motif of OmpA, nor the N-terminal polyproline (43)PPPP(46)
      motif and the Y155 residue of PhoN2 are involved in this interaction while P45,
      P46 and Y155 residues were found to be critical for the correct folding and
      stability of the protein. The relative rapid degradation of these amino acid
      substituted recombinant proteins was found to be due to unknown S. flexneri
      specific protease(s). A model depicting how the PhoN2-OmpA interaction may
      contribute to proper polar IcsA exposition in S. flexneri is presented. 

PMID- 24587294
TI  - The heritability of mating behaviour in a fly and its plasticity in response to
      the threat of sperm competition.
AB  - Phenotypic plasticity is a key mechanism by which animals can cope with rapidly
      changeable environments, but the evolutionary lability of such plasticity remains
      unclear. The socio-sexual environment can fluctuate very rapidly, affecting both
      the frequency of mating opportunities and the level of competition males may
      face. Males of many species show plastic behavioural responses to changes in
      social environment, in particular the presence of rival males. For example,
      Drosophila pseudoobscura males respond to rivals by extending mating duration and
      increasing ejaculate size. Whilst such responses are predicted to be adaptive,
      the extent to which the magnitude of response is heritable, and hence selectable,
      is unknown. We investigated this using isofemale lines of the fruit fly D.
      pseudoobscura, estimating heritability of mating duration in males exposed or not
      to a rival, and any genetic basis to the change in this trait between these
      environments (i.e. degree of plasticity). The two populations differed in
      population sex ratio, and the presence of a sex ratio distorting selfish
      chromosome. We find that mating duration is heritable, but no evidence of
      population differences. We find no significant heritability of plasticity in
      mating duration in one population, but borderline significant heritability of
      plasticity in the second. This difference between populations might be related to
      the presence of the sex ratio distorting selfish gene in the latter population,
      but this will require investigation in additional populations to draw any
      conclusions. We suggest that there is scope for selection to produce an
      evolutionary response in the plasticity of mating duration in response to rivals
      in D. pseudoobscura, at least in some populations. 

PMID- 24587295
TI  - Overlapping Toxoplasma gondii genotypes circulating in domestic animals and
      humans in Southeastern Brazil.
AB  - Although several Toxoplasma gondii genotyping studies have been performed in
      Brazil, studies of isolates from animals in the state of Minas Gerais are rare.
      The objective of this study was to conduct a genotypic characterization of T.
      gondii isolates obtained from dogs, free-range chickens, and humans in Minas
      Gerais and to verify whether the T. gondii genotypes circulating in domestic
      animals correspond to the genotypes detected in humans. Genetic variability was
      assessed by restricted fragment length polymorphism at 11 loci (SAG1, 5'+3'SAG2,
      SAG2 alt, SAG3, BTUB, GRA6, c22-8, c29-2, L358, PK1, and Apico). Twelve different
      genotypes were identified among the 24 isolates studied, including 8 previously
      identified genotypes and 4 new genotypes. The genetic relationship of the 24 T.
      gondii isolates, together with the genotypes previously described from 24 human
      newborns with congenital toxoplasmosis, revealed a high degree of similarity
      among the genotypes circulating in humans and animals in Minas Gerais. The most
      common genotypes among these species were BrII, BrIII, ToxoDB #108, and ToxoDB
      #206. Restricted fragment length polymorphism at the CS3 locus of these 48
      isolates showed that the majority of isolates presented alleles I (50%) or II
      (27%). Isolates harboring allele III at the CS3 locus presented low virulence for
      mice, whereas those harboring alleles I or II presented higher virulence. These
      results confirm the utility of marker CS3 for predicting the virulence of
      Brazilian isolates of T. gondii in mice. No association was found between the
      allele type and clinical manifestations of human congenital toxoplasmosis. This
      is the first report of T. gondii genotyping that verifies the overlapping
      genotypes of T. gondii from humans and animals in the same geographic region of
      Brazil. Our results suggest that there is a common source of infection to the
      species studied, most likely oocysts contaminating the environment. 

PMID- 24587296
TI  - Endogenous methanol regulates mammalian gene activity.
AB  - We recently showed that methanol emitted by wounded plants might function as a
      signaling molecule for plant-to-plant and plant-to-animal communications. In
      mammals, methanol is considered a poison because the enzyme alcohol dehydrogenase
      (ADH) converts methanol into toxic formaldehyde. However, the detection of
      methanol in the blood and exhaled air of healthy volunteers suggests that
      methanol may be a chemical with specific functions rather than a metabolic waste
      product. Using a genome-wide analysis of the mouse brain, we demonstrated that an
      increase in blood methanol concentration led to a change in the accumulation of
      mRNAs from genes primarily involved in detoxification processes and regulation of
      the alcohol/aldehyde dehydrogenases gene cluster. To test the role of ADH in the
      maintenance of low methanol concentration in the plasma, we used the specific ADH
      inhibitor 4-methylpyrazole (4-MP) and showed that intraperitoneal administration
      of 4-MP resulted in a significant increase in the plasma methanol, ethanol and
      formaldehyde concentrations. Removal of the intestine significantly decreased the
      rate of methanol addition to the plasma and suggested that the gut flora may be
      involved in the endogenous production of methanol. ADH in the liver was
      identified as the main enzyme for metabolizing methanol because an increase in
      the methanol and ethanol contents in the liver homogenate was observed after 4-MP
      administration into the portal vein. Liver mRNA quantification showed changes in
      the accumulation of mRNAs from genes involved in cell signalling and
      detoxification processes. We hypothesized that endogenous methanol acts as a
      regulator of homeostasis by controlling the mRNA synthesis. 

PMID- 24587297
TI  - The expression profile of phosphatidylinositol in high spatial resolution imaging
      mass spectrometry as a potential biomarker for prostate cancer.
AB  - High-resolution matrix-assisted laser desorption/ionization imaging mass
      spectrometry (HR-MALDI-IMS) is an emerging application for the comprehensive and
      detailed analysis of the spatial distribution of ionized molecules in situ on
      tissue slides. HR-MALDI-IMS in negative mode in a mass range of m/z 500-1000 was
      performed on optimal cutting temperature (OCT) compound-embedded human prostate
      tissue samples obtained from patients with prostate cancer at the time of radical
      prostatectomy. HR-MALDI-IMS analysis of the 14 samples in the discovery set
      identified 26 molecules as highly expressed in the prostate. Tandem mass
      spectrometry (MS/MS) showed that these molecules included 14
      phosphatidylinositols (PIs), 3 phosphatidylethanolamines (PEs) and 3 phosphatidic
      acids (PAs). Among the PIs, the expression of PI(18:0/18:1), PI(18:0/20:3) and
      PI(18:0/20:2) were significantly higher in cancer tissue than in benign
      epithelium. A biomarker algorithm for prostate cancer was formulated by analyzing
      the expression profiles of PIs in cancer tissue and benign epithelium of the
      discovery set using orthogonal partial least squares discriminant analysis (OPLS
      DA). The sensitivity and specificity of this algorithm for prostate cancer
      diagnosis in the 24 validation set samples were 87.5 and 91.7%, respectively. In
      conclusion, HR-MALDI-IMS identified several PIs as being more highly expressed in
      prostate cancer than benign prostate epithelium. These differences in PI
      expression profiles may serve as a novel diagnostic tool for prostate cancer. 

PMID- 24587298
TI  - Discovery of novel and differentially expressed microRNAs between fetal and adult
      backfat in cattle.
AB  - The posttranscriptional gene regulation mediated by microRNAs (miRNAs) plays an
      important role in various species. Recently, a large number of miRNAs and their
      expression patterns have been identified. However, to date, limited miRNAs have
      been reported to modulate adipogenesis and lipid deposition in beef cattle. Total
      RNAs from Chinese Qinchuan bovine backfat at fetal and adult stages were used to
      construct small RNA libraries for Illumina next-generation sequencing. A total of
      13,915,411 clean reads were obtained from a fetal library and 14,244,946 clean
      reads from an adult library. In total, 475 known and 36 novel miRNA candidates
      from backfat were identified. The nucleotide bias, base editing, and family of
      the known miRNAs were also analyzed. Based on stem-loop qPCR, 15 specific miRNAs
      were detected, and the results showed that bta-miRNAn25 and miRNAn26 were highly
      expressed in backfat tissue, suggesting these small RNAs play a role in the
      development and maintenance of bovine subcutaneous fat tissue. Putative targets
      for miRNAn25 and miRNAn26 were predicted, and the 61 most significant target
      transcripts were related to lipid and fatty acid metabolism. Of interest, the
      canonical pathway and gene networks analyses revealed that PPARalpha/RXRalpha
      activation and LXR/RXR activation were important components of the gene
      interaction hierarchy results. In the present study, we explored the backfat
      miRNAome differences between cattle of different developmental stages, expanding
      the expression repertoire of bovine miRNAs that could contribute to further
      studies on the fat development of cattle. Predication of target genes analysis of
      miRNA25 and miRNA26 also showed potential gene networks that affect lipid and
      fatty acid metabolism. These results may help in the design of new intervention
      strategies to improve beef quality. 

PMID- 24587299
TI  - High expression of protein tyrosine kinase 7 significantly associates with
      invasiveness and poor prognosis in intrahepatic cholangiocarcinoma.
AB  - BACKGROUND: The incidence, prevalence, and mortality of intrahepatic
      cholangiocarcinoma (ICC) are increasing worldwide. Protein tyrosine kinase-7
      (PTK7) is upregulated in many common human cancers. However, its expression in
      ICC has not been studied. The present study aimed to explore the underlying
      mechanism of PTK7 in ICC. MATERIALS AND METHODS: The role of PTK7 was studied in
      vitro by suppressing PTK7 expression in ICC cell lines. The in vivo effect of
      PTK7 was evaluated using a nude mouse model inoculated with a human ICC cell
      line. We also examined the role of PTK7 in human ICC samples. RESULTS: Cells with
      high PTK7 expression exhibited higher proliferation, DNA synthesis, invasion, and
      migration abilities than did cells with low PTK7 expression. The knockdown of
      PTK7 with small interfering RNA (siRNA) in high PTK7 expressing cells resulted in
      impairment of invasion, migration, and DNA synthesis through the regulation of
      several cell-cycle-related proteins. It also induced cell apoptosis and decreased
      phospho-RhoA expression. In a xenograft nude mouse model, PTK7 siRNA resulted in
      a reduction of the tumor size, compared with scrambled siRNA injection. PTK7
      expression was higher in human ICC than in the normal bile duct. Patients with
      low expression of PTK7 had a longer disease-free survival and overall survival
      than those with high expression. CONCLUSIONS: PTK7 expression plays an important
      role in the invasiveness of ICC cells and leads to a poor prognosis in ICC
      patients. Thus, PTK7 can be used as a prognostic indicator, and the inhibition of
      PTK7 expression could be a new therapeutic target for ICC.

PMID- 24587300
TI  - Serum bilirubin concentration in healthy adult North-Europeans is strictly
      controlled by the UGT1A1 TA-repeat variants.
AB  - The major enzyme responsible for the glucuronidation of bilirubin is the uridine
      5'-diphosphoglucose glucuronosyltransferase A1 (UGT1A1) enzyme, and genetic
      variation in the UGT1A1 gene is reported to influence the bilirubin concentration
      in the blood. In this study, we have investigated which gene-/haplotype variants
      may be useful for genetic testing of Gilbert's syndrome. Two groups of samples
      based on serum bilirubin concentrations were obtained from the Nordic Reference
      Interval Project Bio-bank and Database (NOBIDA): the 150 individuals with the
      highest bilirubin (>17.5 umol/L) and the 150 individuals with normal bilirubin
      concentrations (<17.5 umol/L). The individuals were examined for the TA6>TA7
      variant in the UGT1A1 promoter and 7 tag-SNPs in an extended promoter region of
      UGT1A1 (haplotype analysis) and in selected SNPs in candidate genes (SLCO1B3,
      ABCC2 and NUP153). We found significant odds ratios for high bilirubin level for
      all the selected UGT1A1 variants. However, in stepwise multivariate logistic
      regression analysis of all genetic variants together with age, sex, country of
      origin and fasting time, the repeat variants of UGT1A1 TA6>TA7 and SLCO1B3
      rs2117032 T>C were the only variants significantly associated with higher
      bilirubin concentrations. Most individuals with high bilirubin levels were
      homozygous for the TA7-repeat (74%) while only 3% were homozygous for the TA7
      repeat in individuals with normal bilirubin levels. Among individuals
      heterozygous for the TA7-repeat, a low frequent UGT1A1-diplotype harboring the
      rs7564935 G-variant was associated with higher bilirubin levels. In conclusion,
      our results demonstrate that in testing for Gilbert's syndrome, analyzing for the
      homozygous TA7/TA7-genotype would be appropriate. 

PMID- 24587301
TI  - Persistence of botulinum neurotoxin a subtypes 1-5 in primary rat spinal cord
      cells.
AB  - Botulinum neurotoxins (BoNTs) are the most poisonous substances known and cause
      the severe disease botulism. BoNTs have also been remarkably effective as
      therapeutics in treating many neuronal and neuromuscular disorders. One of the
      hallmarks of BoNTs, particularly serotype A, is its long persistence of 2-6
      months in patients at concentrations as low as fM or pM. The mechanisms for this
      persistence are currently unclear. In this study we determined the persistence of
      the BoNT/A subtypes 1 through 5 in primary rat spinal neurons. Remarkably, the
      duration of intracellular enzymatic activity of BoNT/A1, /A2, /A4 and /A5 was
      shown to be at least 10 months. Conversely, the effects of BoNT/A3 were observed
      for up to ~5 months. An intermittent dosing with BoNT/E showed intracellular
      activity of the shorter acting BoNT/E for 2-3 weeks, followed by reoccurrence and
      persistence of BoNT/A-induced SNAP-25 cleavage products. 

PMID- 24587302
TI  - Regularity and predictability of human mobility in personal space.
AB  - Fundamental laws governing human mobility have many important applications such
      as forecasting and controlling epidemics or optimizing transportation systems.
      These mobility patterns, studied in the context of out of home activity during
      travel or social interactions with observations recorded from cell phone use or
      diffusion of money, suggest that in extra-personal space humans follow a high
      degree of temporal and spatial regularity - most often in the form of time
      independent universal scaling laws. Here we show that mobility patterns of older
      individuals in their home also show a high degree of predictability and
      regularity, although in a different way than has been reported for out-of-home
      mobility. Studying a data set of almost 15 million observations from 19 adults
      spanning up to 5 years of unobtrusive longitudinal home activity monitoring, we
      find that in-home mobility is not well represented by a universal scaling law,
      but that significant structure (predictability and regularity) is uncovered when
      explicitly accounting for contextual data in a model of in-home mobility. These
      results suggest that human mobility in personal space is highly stereotyped, and
      that monitoring discontinuities in routine room-level mobility patterns may
      provide an opportunity to predict individual human health and functional status
      or detect adverse events and trends. 

PMID- 24587303
TI  - Delayed remote ischemic postconditioning improves long term sensory motor
      deficits in a neonatal hypoxic ischemic rat model.
AB  - OBJECTIVE: Remote Ischemic Postconditioning (RIPC) is a promising therapeutic
      intervention wherein a sub-lethal ischemic insult induced in one organ (limb)
      improves ischemia in an organ distant to it (brain). The main objective of this
      study was to investigate the long-term functional effects of delayed RIPC in a
      neonatal hypoxia-ischemia (HI) rat model. METHOD: 10 day old rat pups were
      subjected to delayed RIPC treatment and randomized into four groups: 1) Sham, 2)
      HI induced, 3) HI +24 hr delayed RIPC, and 4) HI +24 hr delayed RIPC with three
      consecutive daily treatments. Neurobehavioral tests, brain weights, gross and
      microscopic brain tissue morphologies, and systemic organ weights were evaluated
      at five weeks post surgery. RESULTS: HI induced rats performed significantly
      worse than sham but both groups of delayed RIPC treatment showed improvement of
      sensory motor functions. Furthermore, compared to the HI induced group, the
      delayed RIPC treatment groups showed no further detrimental changes on brain
      tissue, both grossly and morphologically, and no changes on the systemic organ
      weights. CONCLUSION: Delayed RIPC significantly improves long term sensory motor
      deficits in a neonatal HI rat model. A 24 hr delayed treatment does not
      significantly attenuate morphological brain injury but does attenuate sensory
      motor deficits. Sensory motor deficits improve with both a single treatment and
      with three consecutive daily treatments, and the consecutive treatments are
      possibly being more beneficial.

PMID- 24587304
TI  - Overweight and obesity among low-income Muslim Uyghur women in far western China:
      correlations of body mass index with blood lipids and implications in preventive
      public health.
AB  - BACKGROUND: The pandemic of obesity is a global public health concern. Most
      studies on obesity are skewed toward high-income and urban settings and few
      covers low-income populations. This study focused on the prevalence of overweight
      and obesity and their correlations with blood lipids/metabolites/enzymes (bio
      indicators) in a rural community typical of low-income in remote western China.
      METHODS: This study was performed in a Muslim ethnic Uyghur rural community in
      Kashi Prefecture of Xinjiang, about 4,407 km (2,739 miles) away from Beijing.
      Body mass index (BMI) and major blood bio-indicators (25 total items) were
      measured and demographic information was collected from 1,733 eligible healthy
      women aged 21 to 71 yrs, of whom 1,452 had complete data for analysis. More than
      92% of the women lived on US$1.00/day or less. According to the Chinese criteria,
      overweight and obesity were defined as BMI at 24 to <28 kg/m(2) and at >= 28
      kg/m(2), respectively. RESULTS: The average BMI among these low-income women was
      24.0 +/- 4.0 (95% CI, 17.5-33.7) kg/m(2). The prevalence of obesity and
      overweight was high at 15.1% and 28.9%, respectively. Among 25 bio-indicators,
      BMI correlated positively with the levels of 11 bio-indicators including
      triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), total
      cholesterol (TCHOL), glucose (GLU), and uric acid (UA); but negatively with the
      levels of 5 bio-indicators including high-density lipoprotein cholesterol (HDL-C)
      and apolipoprotein A/B (APO A/B). CONCLUSIONS: This is the first investigation
      reporting overweight and obesity being common in low-income Muslim Uyghur women,
      whose BMI correlates with several important blood bio-indicators which are risk
      factors for diabetes and cardiovascular diseases. These findings may help make
      preventive public health policies in Uyghur communities. To prevent diabetes and
      cardiovascular diseases in low-income settings, we therefore propose a cost
      effective, two-step strategy first to screen for obesity and then to screen
      persons with obesity for diabetes and cardiovascular diseases.

PMID- 24587305
TI  - T helper cell subsets specific for Pseudomonas aeruginosa in healthy individuals
      and patients with cystic fibrosis.
AB  - BACKGROUND: We set out to determine the magnitude of antigen-specific memory T
      helper cell responses to Pseudomonas aeruginosa in healthy humans and patients
      with cystic fibrosis. METHODS: Peripheral blood human memory CD4(+) T cells were
      co-cultured with dendritic cells that had been infected with different strains of
      Pseudomonas aeruginosa. The T helper response was determined by measuring
      proliferation, immunoassay of cytokine output, and immunostaining of
      intracellular cytokines. RESULTS: Healthy individuals and patients with cystic
      fibrosis had robust antigen-specific memory CD4(+) T cell responses to
      Pseudomonas aeruginosa that not only contained a Th1 and Th17 component but also
      Th22 cells. In contrast to previous descriptions of human Th22 cells, these
      Pseudomonal-specific Th22 cells lacked the skin homing markers CCR4 or CCR10,
      although were CCR6(+). Healthy individuals and patients with cystic fibrosis had
      similar levels of Th22 cells, but the patient group had significantly fewer Th17
      cells in peripheral blood. CONCLUSIONS: Th22 cells specific to Pseudomonas
      aeruginosa are induced in both healthy individuals and patients with cystic
      fibrosis. Along with Th17 cells, they may play an important role in the pulmonary
      response to this microbe in patients with cystic fibrosis and other conditions.

PMID- 24587306
TI  - Death receptor (DR4) haplotypes are associated with increased susceptibility of
      gallbladder carcinoma in north Indian population.
AB  - BACKGROUND AND AIM: Defective apoptosis is a hallmark of cancer development and
      progression. Death receptors (DR4, FAS) and their ligands (TRAIL, FASL) are
      thought to mediate the major extrinsic apoptotic pathway in the cell. SNPs in
      these genes may lead to defective apoptosis. Hence, the present study aimed to
      investigate the association of functional SNPs of DR4 (rs20575, rs20576 and
      rs6557634), FAS (rs2234767) and FASL (rs763110) with gallbladder cancer (GBC)
      risk. METHODS: This case-control study included 400 GBC and 246 healthy controls
      (HC). Genotyping was carried out by Taqman genotyping assays. Statistical
      analysis was performed by using SPSS ver16. Meta-analysis was performed using
      Comprehensive Meta-analysis software (Version 2.0, BIOSTAT, Englewood, NJ) to
      systematically summarize the possible association of SNP with cancer risk.
      Functional prediction of these variants was carried out using Bioinformatics
      tools (FAST-SNP, F-SNP). False discovery rate (FDR test) was used in multiple
      comparisons. RESULTS: The DR4 C rs20575 A rs20576 A rs6557634, G rs20575 A
      rs20576 G rs6557634 and G rs20575 C rs20576 G rs6557634 haplotypes conferred two
      fold increased risk for GBC. Among these, the DR4 C rs20575 A rs20576 A rs6557634
      haplotype emerged as main factor influencing GBC susceptibility as the risk was
      not modulated by gender or gallstone stratification. Our meta-analysis results
      showed significant association of DR4 rs6557634 with overall cancer risk, GI
      cancers as well as in Caucasians. We didn't find any association of FAS and FASL
      SNPs with GBC susceptibility. CONCLUSIONS: The DR4 haplotype C rs20575 A rs20576
      A rs6557634 represents an important factor accounting the patients susceptibility
      to GBC probably due to decreased apoptosis. However, additional well-designed
      studies with larger sample size focusing on different ethnicities are required to
      further validate the results.

PMID- 24587307
TI  - Characterisation of connexin expression and electrophysiological properties in
      stable clones of the HL-1 myocyte cell line.
AB  - The HL-1 atrial line contains cells blocked at various developmental stages. To
      obtain homogeneous sub-clones and correlate changes in gene expression with
      functional alterations, individual clones were obtained and characterised for
      parameters involved in conduction and excitation-contraction coupling. Northern
      blots for mRNAs coding for connexins 40, 43 and 45 and calcium handling proteins
      (sodium/calcium exchanger, L- and T-type calcium channels, ryanodine receptor 2
      and sarco-endoplasmic reticulum calcium ATPase 2) were performed. Connexin
      expression was further characterised by western blots and immunofluorescence.
      Inward currents were characterised by voltage clamp and conduction velocities
      measured using microelectrode arrays. The HL-1 clones had similar sodium and
      calcium inward currents with the exception of clone 2 which had a significantly
      smaller calcium current density. All the clones displayed homogenous propagation
      of electrical activity across the monolayer correlating with the levels of
      connexin expression. Conduction velocities were also more sensitive to inhibition
      of junctional coupling by carbenoxolone (~ 80%) compared to inhibition of the
      sodium current by lidocaine (~ 20%). Electrical coupling by gap junctions was the
      major determinant of conduction velocities in HL-1 cell lines. In summary we have
      isolated homogenous and stable HL-1 clones that display characteristics distinct
      from the heterogeneous properties of the original cell line.

PMID- 24587308
TI  - Intracellular Acid-extruding regulators and the effect of lipopolysaccharide in
      cultured human renal artery smooth muscle cells.
AB  - Homeostasis of the intracellular pH (pHi) in mammalian cells plays a pivotal role
      in maintaining cell function. Thus far, the housekeeping Na(+)-H(+) exchanger
      (NHE) and the Na(+)-HCO3(-) co-transporter (NBC) have been confirmed in many
      mammalian cells as major acid extruders. However, the role of acid-extruding
      regulators in human renal artery smooth muscle cells (HRASMCs) remains unclear.
      It has been demonstrated that lipopolysaccharide (LPS)-induced vascular occlusion
      is associated with the apoptosis, activating calpain and increased [Ca(2+)]i that
      are related to NHE1 activity in endothelia cells. This study determines the acid
      extruding mechanisms and the effect of LPS on the resting pHi and active acid
      extruders in cultured HRASMCs. The mechanism of pHi recovery from intracellular
      acidosis (induced by NH4Cl-prepulse) is determined using BCECF-fluorescence in
      cultured HRASMCs. It is seen that (a) the resting pHi is 7.19 +/- 0.03 and 7.10
      +/- 0.02 for HEPES- and CO2/HCO3(-)- buffered solution, respectively; (b) apart
      from the housekeeping NHE1, another Na(+)-coupled HCO3(-) transporter i.e. NBC,
      functionally co-exists to achieve acid-equivalent extrusion; (c) three different
      isoforms of NBC: NBCn1 (SLC4A7; electroneutral), NBCe1 (SLC4A4; electrogenic) and
      NBCe2 (SLC4A5), are detected in protein/mRNA level; and (d) pHi and NHE protein
      expression/activity are significantly increased by LPS, in both a dose- and time-
      dependent manner, but NBCs protein expression is not. In conclusion, it is
      demonstrated, for the first time, that four pHi acid-extruding regulators: NHE1,
      NBCn1, NBCe1 and NBCe2, co-exist in cultured HRASMCs. LPS also increases cellular
      growth, pHi and NHE in a dose- and time-dependent manner.

PMID- 24587310
TI  - Twelve years of change in coastal upwelling along the central-northern coast of
      Chile: spatially heterogeneous responses to climatic variability.
AB  - We use time-series analyses to characterize the effects of recent climate
      variability upon the local physical conditions at 11 study sites along the
      northern-central coast of Chile (29-34 degrees S). Environmental indices show
      that the 1 degrees  Bakun upwelling index in this coastal region has fluctuated
      in time, starting from a stable period around the 1980's, peaking during the mid
      90s, decreasing during the next ten years and increasing at a steep rate since
      2010. Upwelling intensity decreased with increasing latitude, showing also a
      negative correlation with climate patterns (El Nino3 sea surface temperature-SST
      anomalies and the Multivariate El Nino Index). We hypothesize that the impacts of
      climate variability on upwelling events seem to be spatially heterogeneous along
      the region. Non-sheltered locations and, particularly, sites on prominent
      headlands show an immediate (lag = 0) and negative correlation between local SST,
      upwelling events and wind stress. We suggest that near-shore thermal conditions
      are closely coupled to large-scale forcing of upwelling variability and that this
      influence is modulated through local topographic factors.

PMID- 24587309
TI  - Morphological divergence driven by predation environment within and between
      species of Brachyrhaphis fishes.
AB  - Natural selection often results in profound differences in body shape among
      populations from divergent selective environments. Predation is a well-studied
      driver of divergence, with predators having a strong effect on the evolution of
      prey body shape, especially for traits related to escape behavior. Comparative
      studies, both at the population level and between species, show that the presence
      or absence of predators can alter prey morphology. Although this pattern is well
      documented in various species or population pairs, few studies have tested for
      similar patterns of body shape evolution at multiple stages of divergence within
      a taxonomic group. Here, we examine morphological divergence associated with
      predation environment in the livebearing fish genus Brachyrhaphis. We compare
      differences in body shape between populations of B. rhabdophora from different
      predation environments to differences in body shape between B. roseni and B.
      terrabensis (sister species) from predator and predator free habitats,
      respectively. We found that in each lineage, shape differed between predation
      environments, consistent with the hypothesis that locomotor function is optimized
      for either steady swimming (predator free) or escape behavior (predator).
      Although differences in body shape were greatest between B. roseni and B.
      terrabensis, we found that much of the total morphological diversification
      between these species had already been achieved within B. rhabdophora (29% in
      females and 47% in males). Interestingly, at both levels of divergence we found
      that early in ontogenetic development, females differed in shape between
      predation environments; however, as females matured, their body shapes converged
      on a similar phenotype, likely due to the constraints of pregnancy. Finally, we
      found that body shape varies with body size in a similar way, regardless of
      predation environment, in each lineage. Our findings are important because they
      provide evidence that the same source of selection can drive similar phenotypic
      divergence independently at multiple divergence levels. 

PMID- 24587311
TI  - Urotensin II induces interleukin 8 expression in human umbilical vein endothelial
      cells.
AB  - BACKGROUND: Urotensin II (U-II), an 11-amino acid peptide, exerts a wide range of
      actions in cardiovascular systems. Interleukin-8 (IL-8) is secreted by
      endothelial cells, thereby enhancing endothelial cell survival, proliferation,
      and angiogenesis. However, the interrelationship between U-II and IL-8 as well as
      the detailed intracellular mechanism of U-II in vascular endothelial cells remain
      unclear. The aim of this study was to investigate the effect of U-II on IL-8
      expression and to explore its intracellular mechanism in human umbilical vein
      endothelial cells. METHODS/PRINCIPAL FINDINGS: Primary human umbilical vein
      endothelial cells were used. Expression of IL-8 was determined by real-time
      quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, and
      luciferase reporter assay. Western blot analyses and experiments with specific
      inhibitors were performed to reveal the downstream signaling pathways as
      concerned. U-II increased the mRNA/protein levels of IL-8 in human umbilical vein
      endothelial cells. The U-II effects were significantly inhibited by its receptor
      antagonist [Orn(5)]-URP. Western blot analyses and experiments with specific
      inhibitors indicated the involvement of phosphorylation of p38 mitogen-activated
      protein kinase and extracellular signal-regulated kinase in U-II-induced IL-8
      expression. Luciferase reporter assay further revealed that U-II induces the
      transcriptional activity of IL-8. The site-directed mutagenesis indicated that
      the mutation of AP-1 and NF-kB binding sites reduced U-II-increased IL-8 promoter
      activities. Proliferation of human umbilical vein endothelial cells induced by U
      II could be inhibited significantly by IL-8 RNA interference.
      CONCLUSION/SIGNIFICANCE: The results show that U-II induces IL-8 expression in
      human umbilical vein endothelial cells via p38 mitogen-activated protein kinase
      and extracellular signal-regulated kinase signaling pathways and IL-8 is involved
      in the U-II-induced proliferation of human umbilical vein endothelial cells.

PMID- 24587312
TI  - Gene expression changes for antioxidants pathways in the mouse cochlea: relations
      to age-related hearing deficits.
AB  - Age-related hearing loss - presbycusis - is the number one neurodegenerative
      disorder and top communication deficit of our aged population. Like many aging
      disorders of the nervous system, damage from free radicals linked to production
      of reactive oxygen and/or nitrogen species (ROS and RNS, respectively) may play
      key roles in disease progression. The efficacy of the antioxidant systems, e.g.,
      glutathione and thioredoxin, is an important factor in pathophysiology of the
      aging nervous system. In this investigation, relations between the expression of
      antioxidant-related genes in the auditory portion of the inner ear - cochlea, and
      age-related hearing loss was explored for CBA/CaJ mice. Forty mice were
      classified into four groups according to age and degree of hearing loss. Cochlear
      mRNA samples were collected and cDNA generated. Using Affymetrix(r) GeneChip, the
      expressions of 56 antioxidant-related gene probes were analyzed to estimate the
      differences in gene expression between the four subject groups. The expression of
      Glutathione peroxidase 6, Gpx6; Thioredoxin reductase 1, Txnrd1; Isocitrate
      dehydrogenase 1, Idh1; and Heat shock protein 1, Hspb1; were significantly
      different, or showed large fold-change differences between subject groups. The
      Gpx6, Txnrd1 and Hspb1 gene expression changes were validated using qPCR. The
      Gpx6 gene was upregulated while the Txnrd1 gene was downregulated with
      age/hearing loss. The Hspb1 gene was found to be downregulated in middle-aged
      animals as well as those with mild presbycusis, whereas it was upregulated in
      those with severe presbycusis. These results facilitate development of future
      interventions to predict, prevent or slow down the progression of presbycusis. 

PMID- 24587313
TI  - IL-17 induces an expanded range of downstream genes in reconstituted human
      epidermis model.
AB  - BACKGROUND: IL-17 is the defining cytokine of the Th17, Tc17, and gammadelta T
      cell populations that plays a critical role in mediating inflammation and
      autoimmunity. Psoriasis vulgaris is an inflammatory skin disease mediated by Th1
      and Th17 cytokines with relevant contributions of IFN-gamma, TNF-alpha, and IL
      17. Despite the pivotal role IL-17 plays in psoriasis, and in contrast to the
      other key mediators involved in the psoriasis cytokine cascade that are capable
      of inducing broad effects on keratinocytes, IL-17 was demonstrated to regulate
      the expression of a limited number of genes in monolayer keratinocytes cultured
      in vitro. METHODOLOGY/PRINCIPAL FINDINGS: Given the clinical efficacy of anti-IL
      17 agents is associated with an impressive reduction in a large set of
      inflammatory genes, we sought a full-thickness skin model that more closely
      resemble in vivo epidermal architecture. Using a reconstructed human epidermis
      (RHE), IL-17 was able to upregulate 419 gene probes and downregulate 216 gene
      probes. As possible explanation for the increased gene induction in the RHE model
      is that C/CAAT-enhancer-binding proteins (C/EBP) -beta, the transcription factor
      regulating IL-17-responsive genes, is expressed preferentially in differentiated
      keratinocytes. CONCLUSIONS/SIGNIFICANCE: The genes identified in IL-17-treated
      RHE are likely relevant to the IL-17 effects in psoriasis, since ixekizumab (anti
      IL-17A agent) strongly suppressed the "RHE" genes in psoriasis patients treated
      in vivo with this IL-17 antagonist.

PMID- 24587314
TI  - Prenatal influences on size, velocity and tempo of infant growth: findings from
      three contemporary cohorts.
AB  - BACKGROUND: Studying prenatal influences of early life growth is relevant to life
      course epidemiology as some of its features have been linked to the onset of
      later diseases. METHODS: We studied the association between prenatal maternal
      characteristics (height, age, parity, education, pre-pregnancy body mass index
      (BMI), smoking, gestational diabetes and hypertension) and offspring weight
      trajectories in infancy using SuperImposition by Translation And Rotation (SITAR)
      models, which parameterize growth in terms of three biologically interpretable
      parameters: size, velocity and tempo. We used data from three contemporary
      cohorts based in Portugal (GXXI, n=738), Italy (NINFEA, n=2,925), and Chile
      (GOCS, n=959). RESULTS: Estimates were generally consistent across the cohorts
      for maternal height, age, parity and pre-pregnancy overweight/obesity. Some
      exposures only affected one growth parameter (e.g. maternal height (per cm): 0.4%
      increase in size (95% confidence interval (CI):0.3; 0.5)), others were either
      found to affect size and velocity (e.g. pre-pregnancy underweight vs normal
      weight: smaller size (-4.9%, 95% CI:-6.5; -3.3), greater velocity (5.9%, 95%
      CI:1.9;10.0)), or to additionally influence tempo (e.g. pre-pregnancy
      overweight/obesity vs normal weight: increased size (7.9%, 95% CI:4.9;10.8),
      delayed tempo (0.26 months, 95% CI:0.11;0.41), decreased velocity (-4.9%, 95% CI:
      -10.8;0.9)). CONCLUSIONS: By disentangling the growth parameters of size,
      velocity and tempo, we found that prenatal maternal characteristics, especially
      maternal smoking, pre-pregnancy overweight and underweight, parity and
      gestational hypertension, are associated with different aspects of infant weight
      growth. These results may offer insights into the mechanisms governing infant
      growth.

PMID- 24587315
TI  - Generalized drivers in the mammalian endangerment process.
AB  - An important challenge for conservation today is to understand the endangerment
      process and identify any generalized patterns in how threats occur and aggregate
      across taxa. Here we use a global database describing main current external
      threats in mammals to evaluate the prevalence of distinct threatening processes,
      primarily of anthropogenic origin, and to identify generalized drivers of
      extinction and their association with vulnerability status and intrinsic species'
      traits. We detect several primary threat combinations that are generally
      associated with distinct species. In particular, large and widely distributed
      mammals are affected by combinations of direct exploitation and threats
      associated with increasing landscape modification that go from logging to intense
      human land-use. Meanwhile, small, narrowly distributed species are affected by
      intensifying levels of landscape modification but are not directly exploited. In
      general more vulnerable species are affected by a greater number of threats,
      suggesting increased extinction risk is associated with the accumulation of
      external threats. Overall, our findings show that endangerment in mammals is
      strongly associated with increasing habitat loss and degradation caused by human
      land-use intensification. For large and widely distributed mammals there is the
      additional risk of being hunted. 

PMID- 24587316
TI  - Tumour necrosis factor-alpha regulates human eosinophil apoptosis via ligation of
      TNF-receptor 1 and balance between NF-kappaB and AP-1.
AB  - Eosinophils play a central role in asthma. The present study was performed to
      investigate the effect of tumour necrosis factor-alpha (TNF-alpha) on longevity
      of isolated human eosinophils. In contrast to Fas, TNF-alpha inhibited eosinophil
      apoptosis as evidenced by a combination of flow cytometry, DNA fragmentation
      assay and morphological analyses. The effect of TNF-alpha on eosinophil apoptosis
      was reversed by a TNF-alpha neutralising antibody. The anti-apoptotic effect of
      TNF-alpha was not due to autocrine release of known survival-prolonging cytokines
      interleukins 3 and 5 or granulocyte-macrophage-colony-stimulating factor as their
      neutralisation did not affect the effect of TNF-alpha. The anti-apoptotic signal
      was mediated mainly by the TNF-receptor 1. TNF-alpha induced phosphorylation and
      degradation of IkappaB and an increase in NF-kappaB DNA-binding activity. The
      survival-prolonging effect of TNF-alpha was reversed by inhibitors of NF-kappaB
      pyrrolidinedithiocarbamate and gliotoxin and by an inhibitor of IkappaB kinase,
      BMS-345541. TNF-alpha induced also an increase in AP-1 DNA-binding activity and
      the antiapoptotic effect of TNF-alpha was potentiated by inhibitors of AP-1, SR
      11302 and tanshinone IIA and by an inhibitor of c-jun-N-terminal kinase,
      SP600125, which is an upstream kinase activating AP-1. Our results thus suggest
      that TNF-alpha delays human eosinophil apoptosis via TNF-receptor 1 and the
      resulting changes in longevity depend on yin-yang balance between activation of
      NF-kappaB and AP-1. 

PMID- 24587317
TI  - Both 25-hydroxyvitamin-D3 and 1,25-dihydroxyvitamin-D3 reduces inflammatory
      response in human periodontal ligament cells.
AB  - Periodontitis is an inflammatory disease leading to the destruction of
      periodontal tissue. Vitamin D3 is an important hormone involved in the
      preservation of serum calcium and phosphate levels, regulation of bone metabolism
      and inflammatory response. Recent studies suggest that vitamin D3 metabolism
      might play a role in the progression of periodontitis. The aim of the present
      study was to examine the effects of 25(OH)D3, which is stable form of vitamin D3
      in blood, and biologically active form 1,25(OH)2D3 on the production of
      interleukin-6 (IL-6), interleukin-8 (IL-8), and monocyte chemotactic protein-1
      (MCP-1) by cells of periodontal ligament. Commercially available human
      periodontal ligament fibroblasts (hPdLF) and primary human periodontal ligament
      cells (hPdLC) were used. Cells were stimulated with either Porphyromonas
      gingivalis lipopolysaccharide (LPS) or heat-killed P. ginigvalis in the presence
      or in the absence of 25(OH)D3 or 1,25(OH)2D3 at concentrations of 10-100 nM.
      Stimulation of cells with either P. gingivalis LPS or heat-killed P. gingivalis
      resulted in a significant increase of the expression levels of IL-6, IL-8, and
      MCP-1 in gene as well as in protein levels, measured by qPCR and ELISA,
      respectively. The production of these pro-inflammatory mediators in hPdLF was
      significantly inhibited by both 25(OH)D3 and 1,25(OH)2D3 in a dose-dependent
      manner. In primary hPdLCs, both 25(OH)D3 and 1,25(OH)2D3 inhibited the production
      of IL-8 and MCP-1 but have no significant effect on the IL-6 production. The
      effect of both 25(OH)D3 and 1,25(OH)2D3 was abolished by specific knockdown of
      vitamin D3 receptor by siRNA. Our data suggest that vitamin D3 might play an
      important role in the modulation of periodontal inflammation via regulation of
      cytokine production by cells of periodontal ligament. Further studies are
      required for better understanding of the extents of this anti-inflammatory effect
      and its involvement in the progression of periodontal disease. 

PMID- 24587318
TI  - The impact of individual depressive symptoms on impairment of psychosocial
      functioning.
AB  - Previous studies have established that scores on Major Depressive Disorder scales
      are correlated with measures of impairment of psychosocial functioning. It
      remains unclear, however, whether individual depressive symptoms vary in their
      effect on impairment, and if so, what the magnitude of these differences might
      be. We analyzed data from 3,703 depressed outpatients in the first treatment
      stage of the Sequenced Treatment Alternatives to Relieve Depression (STAR*D)
      study. Participants reported on the severity of 14 depressive symptoms, and
      stated to what degree their depression impaired psychosocial functioning (in
      general, and in the five domains work, home management, social activities,
      private activities, and close relationships). We tested whether symptoms differed
      in their associations with impairment, estimated unique shared variances of each
      symptom with impairment to assess the degree of difference, and examined whether
      symptoms had variable impacts across impairment domains. Our results show that
      symptoms varied substantially in their associations with impairment, and
      contributed to the total explained variance in a range from 0.7% (hypersomnia) to
      20.9% (sad mood). Furthermore, symptoms had significantly different impacts on
      the five impairment domains. Overall, sad mood and concentration problems had the
      highest unique associations with impairment and were among the most debilitating
      symptoms in all five domains. Our findings are in line with a growing chorus of
      voices suggesting that symptom sum-scores obfuscate relevant differences between
      depressed patients and that substantial rewards will come from close attention to
      individual depression symptoms. 

PMID- 24587319
TI  - The efficacy and safety of different kinds of laparoscopic cholecystectomy: a
      network meta analysis of 43 randomized controlled trials.
AB  - BACKGROUND AND OBJECTIVE: We conducted a network meta analysis (NMA) to compare
      different kinds of laparoscopic cholecystectomy [LC] (single port [SPLC], two
      ports [2PLC], three ports [3PLC], and four ports laparoscopic cholecystectomy
      [4PLC], and four ports mini-laparoscopic cholecystectomy [mini-4PLC]). METHODS:
      PubMed, the Cochrane library, EMBASE, and ISI Web of Knowledge were searched to
      find randomized controlled trials [RCTs]. Direct pair-wise meta analysis (DMA),
      indirect treatment comparison meta analysis (ITC) and NMA were conducted to
      compare different kinds of LC. RESULTS: We included 43 RCTs. The risk of bias of
      included studies was high. DMA showed that SPLC was associated with more
      postoperative complications, longer operative time, and higher cosmetic score
      than 4PLC, longer operative time and higher cosmetic score than 3PLC, more
      postoperative complications than mini-4PLC. Mini-4PLC was associated with longer
      operative time than 4PLC. ITC showed that 3PLC was associated with shorter
      operative time than mini-4PLC, and lower postoperative pain level than 2PLC. 2PLC
      was associated with fewer postoperative complications and longer hospital stay
      than SPLC. NMA showed that SPLC was associated with more postoperative
      complications than mini-4PLC, and longer operative time than 4PLC. CONCLUSION:
      The rank probability plot suggested 4PLC might be the worst due to the highest
      level of postoperative pain, longest hospital stay, and lowest level of cosmetic
      score. The best one might be mini-4PLC because of highest level of cosmetic
      score, and fewest postoperative complications, or SPLC because of lowest level of
      postoperative pain and shortest hospital stay. But more studies are needed to
      determine which will be better between mini-4PLC and SPLC.

PMID- 24587320
TI  - The effects of smoking on levels of endothelial progenitor cells and
      microparticles in the blood of healthy volunteers.
AB  - BACKGROUND: Cigarette smoking, both active and passive, is one of the leading
      causes of morbidity and mortality in cardiovascular disease. To assess the impact
      of brief smoking on the vasculature, we determined levels of circulating
      endothelial progenitor cells (EPCs) and circulating microparticles (MPs)
      following the smoking of one cigarette by young, healthy intermittent smokers.
      MATERIALS AND METHODS: 12 healthy volunteers were randomized to either smoking or
      not smoking in a crossover fashion. Blood sampling was performed at baseline, 1,
      4 and 24 hours following smoking/not smoking. The numbers of EPCs and MPs were
      determined by flow cytometry. MPs were measured from platelets, leukocytes and
      endothelial cells. Moreover, MPs were also labelled with anti-HMGB1 and SYTO 13
      to assess the content of nuclear molecules. RESULTS: Active smoking of one
      cigarette caused an immediate and significant increase in the numbers of
      circulating EPCs and MPs of platelet-, endothelial- and leukocyte origin. Levels
      of MPs containing nuclear molecules were increased, of which the majority were
      positive for CD41 and CD45 (platelet- and leukocyte origin). CD144 (VE-cadherin)
      or HMGB1 release did not significantly change during active smoking. CONCLUSION:
      Brief active smoking of one cigarette generated an acute release of EPC and MPs,
      of which the latter contained nuclear matter. Together, these results demonstrate
      acute effects of cigarette smoke on endothelial, platelet and leukocyte function
      as well as injury to the vascular wall.

PMID- 24587321
TI  - Baicalein reduces the invasion of glioma cells via reducing the activity of p38
      signaling pathway.
AB  - Baicalein, one of the major flavonids in Scutellaria baicalensis, has
      historically been used in anti-inflammatory and anti-cancer therapies. However,
      the anti-metastatic effect and related mechanism(s) in glioma are still unclear.
      In this study, we thus utilized glioma cell lines U87MG and U251MG to explore the
      effect of baicalein. We found that administration of baicalein significantly
      inhibited migration and invasion of glioma cells. In addition, after treating
      with baicalein for 24 h, there was a decrease in the levels of matrix
      metalloproteinase-2 (MMP-2) and MMP-9 expression as well as proteinase activity
      in glioma cells. Conversely, the expression of tissue inhibitor of
      metalloproteinase-1 (TIMP-1) and TIMP-2 was increased in a dose-dependent manner.
      Moreover, baicalein treatment significantly decreased the phosphorylated level of
      p38, but not ERK1/2, JNK1/2 and PI3K/Akt. Combined treatment with a p38 inhibitor
      (SB203580) and baicalein resulted in the synergistic reduction of MMP-2 and MMP-9
      expression and then increase of TIMP-1 and TIMP-2 expression; and the invasive
      capabilities of U87MG cells were also inhibited. However, p38 chemical activator
      (anisomycin) could block these effects produced by baicalein, suggesting
      baicalein directly downregulate the p38 signaling pathway. In conclusion,
      baicalein inhibits glioma cells invasion and metastasis by reducing cell motility
      and migration via suppression of p38 signaling pathway, suggesting that baicalein
      is a potential therapeutic agent for glioma.

PMID- 24587322
TI  - Biomechanics of forearm rotation: force and efficiency of pronator teres.
AB  - Biomechanical models are useful to assess the effect of muscular forces on bone
      structure. Using skeletal remains, we analyze pronator teres rotational
      efficiency and its force components throughout the entire flexion-extension and
      pronation-supination ranges by means of a new biomechanical model and 3D imaging
      techniques, and we explore the relationship between these parameters and skeletal
      structure. The results show that maximal efficiency is the highest in full elbow
      flexion and is close to forearm neutral position for each elbow angle. The
      vertical component of pronator teres force is the highest among all components
      and is greater in pronation and elbow extension. The radial component becomes
      negative in pronation and reaches lower values as the elbow flexes. Both
      components could enhance radial curvature, especially in pronation. The model
      also enables to calculate efficiency and force components simulating changes in
      osteometric parameters. An increase of radial curvature improves efficiency and
      displaces the position where the radial component becomes negative towards the
      end of pronation. A more proximal location of pronator teres radial enthesis and
      a larger humeral medial epicondyle increase efficiency and displace the position
      where this component becomes negative towards forearm neutral position, which
      enhances radial curvature. Efficiency is also affected by medial epicondylar
      orientation and carrying angle. Moreover, reaching an object and bringing it
      close to the face in a close-to-neutral position improve efficiency and entail an
      equilibrium between the forces affecting the elbow joint stability. When the
      upper-limb skeleton is used in positions of low efficiency, implying unbalanced
      force components, it undergoes plastic changes, which improve these parameters.
      These findings are useful for studies on ergonomics and orthopaedics, and the
      model could also be applied to fossil primates in order to infer their locomotor
      form. Moreover, activity patterns in human ancient populations could be deduced
      from parameters reported here. 

PMID- 24587324
TI  - Is cryoballoon ablation preferable to radiofrequency ablation for treatment of
      atrial fibrillation by pulmonary vein isolation? A meta-analysis.
AB  - OBJECTIVE: Currently radiofrequency and cryoballoon ablations are the two
      standard ablation systems used for catheter ablation of atrial fibrillation;
      however, there is no universal consensus on which ablation is the optimal choice.
      We therefore sought to undertake a meta-analysis with special emphases on
      comparing the efficacy and safety between cryoballoon and radiofrequency
      ablations by synthesizing published clinical trials. METHODS AND RESULTS:
      Articles were identified by searching the MEDLINE and EMBASE databases before
      September 2013, by reviewing the bibliographies of eligible reports, and by
      consulting with experts in this field. Data were extracted independently and in
      duplicate. There were respectively 469 and 635 patients referred for cryoballoon
      and radiofrequency ablations from 14 qualified clinical trials. Overall analyses
      indicated that cryoballoon ablation significantly reduced fluoroscopic time and
      total procedure time by a weighted mean of 14.13 (95% confidence interval [95%
      CI]: 2.82 to 25.45; P = 0.014) minutes and 29.65 (95% CI: 8.54 to 50.77; P =
      0.006) minutes compared with radiofrequency ablation, respectively, whereas
      ablation time in cryoballoon ablation was nonsignificantly elongated by a
      weighted mean of 11.66 (95% CI: -10.71 to 34.04; P = 0.307) minutes. Patients
      referred for cryoballoon ablation had a high yet nonsignificant success rate of
      catheter ablation compared with cryoballoon ablation (odds ratio; 95% CI; P:
      1.34; 0.53 to 3.36; 0.538), and cryoballoon ablation was also found to be
      associated with the relatively low risk of having recurrent atrial fibrillation
      (0.75; 0.3 to 1.88; 0.538) and major complications (0.46; 0.11 to 1.83; 0.269).
      There was strong evidence of heterogeneity and low probability of publication
      bias. CONCLUSION: Our findings demonstrate greater improvement in fluoroscopic
      time and total procedure duration for atrial fibrillation patients referred for
      cryoballoon ablation than those for radiofrequency ablation.

PMID- 24587323
TI  - Poly(ADP-ribose)polymerase activity controls plant growth by promoting leaf cell
      number.
AB  - A changing global environment, rising population and increasing demand for
      biofuels are challenging agriculture and creating a need for technologies to
      increase biomass production. Here we demonstrate that the inhibition of poly (ADP
      ribose) polymerase activity is a promising technology to achieve this under non
      stress conditions. Furthermore, we investigate the basis of this growth
      enhancement via leaf series and kinematic cell analysis as well as single leaf
      transcriptomics and plant metabolomics under non-stress conditions. These data
      indicate a regulatory function of PARP within cell growth and potentially
      development. PARP inhibition enhances growth of Arabidopsis thaliana by enhancing
      the cell number. Time course single leaf transcriptomics shows that PARP
      inhibition regulates a small subset of genes which are related to growth
      promotion, cell cycle and the control of metabolism. This is supported by
      metabolite analysis showing overall changes in primary and particularly secondary
      metabolism. Taken together the results indicate a versatile function of PARP
      beyond its previously reported roles in controlling plant stress tolerance and
      thus can be a useful target for enhancing biomass production. 

PMID- 24587325
TI  - Intracellular Propionibacterium acnes infection in glandular epithelium and
      stromal macrophages of the prostate with or without cancer.
AB  - BACKGROUND: Recent reports on Propionibacterium acnes (P. acnes) suggest that
      this bacterium is prevalent in the prostate, is associated with acute and chronic
      prostatic inflammation, and might have a role in prostate carcinogenesis.
      METHODS: To evaluate the pathogenic role of this indigenous bacterium, we
      screened for the bacterium in radical prostatectomy specimens using enzyme
      immunohistochemistry with a novel P. acnes-specific monoclonal antibody (PAL
      antibody), together with an anti-nuclear factor-kappa B (NF-kappaB) antibody. We
      examined formalin-fixed and paraffin-embedded tissue sections of radical
      prostatectomy specimens from 28 patients with prostate cancer and 18 age-matched
      control patients with bladder cancer, but without prostate cancer. RESULTS:
      Immunohistochemistry with the PAL antibody revealed small round bodies within
      some non-cancerous glandular epithelium and stromal macrophages in most prostate
      samples. Prostate cancer samples had higher frequencies of either cytoplasmic P.
      acnes or nuclear NF-kappaB expression of glandular epithelium and higher numbers
      of stromal macrophages with P. acnes than control samples. These parameters were
      also higher in the peripheral zone than in the transitional zone of the prostate,
      especially in prostate cancer samples. Nuclear NF-kappaB expression was more
      frequent in glands with P. acnes than in glands without P. acnes. The number of
      stromal macrophages with the bacterium correlated with the grade of chronic
      inflammation in both the PZ and TZ areas and with the grade of acute inflammation
      in the TZ area. CONCLUSIONS: Immunohistochemical analysis with a novel monoclonal
      antibody for detecting P. acnes in the prostate suggested that intraepithelial P.
      acnes infection in non-cancerous prostate glands and inflammation caused by the
      bacterium may contribute to the development of prostate cancer.

PMID- 24587327
TI  - Stomach temperature records reveal nursing behaviour and transition to solid food
      consumption in an unweaned mammal, the harbour seal pup (Phoca vitulina).
AB  - Knowledge of milk transfer from mother to offspring and early solid food
      ingestions in mammals allows for a greater understanding of the factors affecting
      transition to nutritional independence and pre-weaning growth and survival. Yet
      studies monitoring suckling behaviour have often relied on visual observations,
      which might not accurately represent milk intake. We assessed the use of stomach
      temperature telemetry to monitor suckling and foraging behaviour in free-ranging
      harbour seal (Phoca vitulina) pups during lactation. Stomach temperature declines
      were analysed using principal component and cluster analyses, as well as trials
      using simulated stomachs resulting in a precise classification of stomach
      temperature drops into milk, seawater and solid food ingestions. Seawater and
      solid food ingestions represented on average 15.3+/-1.6% [0-40.0%] and 0.7+/-0.2%
      [0-13.0%], respectively, of individual ingestions. Overall, 63.7% of milk
      ingestions occurred while the pups were in the water, of which 13.9% were
      preceded by seawater ingestion. The average time between subsequent ingestions
      was significantly less for seawater than for milk ingestions. These results
      suggest that seawater ingestion might represent collateral ingestion during
      aquatic suckling attempts. Alternatively, as solid food ingestions (n = 19) were
      observed among 7 pups, seawater ingestion could result from missed prey capture
      attempts. This study shows that some harbour seals start ingesting prey while
      still being nursed, indicating that weaning occurs more gradually than previously
      thought in this species. Stomach temperature telemetry represents a promising
      method to study suckling behaviour in wild mammals and transition to nutritional
      independence in various endotherm species. 

PMID- 24587326
TI  - Stereotactic body radiotherapy-induced arterial hypervascularity of non-tumorous
      hepatic parenchyma in patients with hepatocellular carcinoma: potential pitfalls
      in tumor response evaluation on multiphase computed tomography.
AB  - PURPOSE: To evaluate temporal changes in contrast enhancement patterns of non
      tumorous hepatic parenchyma with a focus on arterial hypervascularity on
      multiphase computed tomography (CT) in patients with hepatocellular carcinoma
      (HCC) treated with stereotactic body radiotherapy (SBRT). METHODS: We
      retrospectively identified 61 patients who had undergone multiphase contrast
      enhanced CT at one, three, and six months after SBRT. Irradiated versus non
      irradiated liver parenchyma was delineated by cross-correlation with the dose
      volume histogram of SBRT plan. Serial changes in the contrast enhancement
      patterns of the irradiated versus non-irradiated liver parenchyma were evaluated
      by two abdominal radiologists in consensus. We compared the frequency of the
      contrast enhancement patterns according to the follow-up period using the Fisher
      Freeman-Halton exact test. RESULTS: The irradiated non-tumorous hepatic
      parenchyma showed that the prevalence of arterial hypervascularity increased
      during the follow-up period (P<.01): 11.5% (7/61) in one, 45.9% (28/61) in three,
      and 54.1% (33/61) in six months. Contrast wash-out on the delayed phase was
      uncommon: 1.6% (1/61) in one, 3.3% (2/61) in three, and 0% in six months.
      CONCLUSION: The incidence of arterial hypervascularity of the irradiated hepatic
      parenchyma gradually increased until six months after SBRT, which could interfere
      with the accurate evaluation of treatment response. The lack of wash-out on the
      delayed phase in the hypervascular area would distinguish SBRT-related change
      from residual/recurred HCC.

PMID- 24587328
TI  - Monocytes expand with immune dysregulation and is associated with insulin
      resistance in older individuals with chronic HIV.
AB  - BACKGROUND: Rates of insulin resistance are increased in HIV-infected patients on
      stable antiretroviral therapy (ART). Such increase may partially be due to HIV
      induced immune dysregulation involving monocytes (MO) and its subsets. MATERIALS
      AND METHODS: Cross-sectional analysis of 141 HIV-infected subjects age >= 40
      years on stable ART. Homeostatic model assessment-insulin resistance (HOMA-IR)
      and rates of metabolic syndrome were calculated. Subjects were classified by
      fasting glucose and oral glucose tolerance test (OGTT) into clinical diabetes
      categories. Multi-parametric flow cytometry was used to determine MO subset
      percentages: [classical (CD14(++)CD16(-)), intermediate (CD14(++)CD16(+)), non
      classical (CD14(low/+)CD16(++)), and a recently identified fourth
      (CD14(low/+)CD16(-)) 'transitional' MO subset] and percentage of activated
      (CD38(+)HLA-DR(+)) CD8 T cells. Absolute levels of cells were calculated using
      clinical CBC and T cell subset data. Multiple plasma soluble biomarkers were
      assessed by Luminex technology. RESULTS: Median age 50 years, CD4 count (percent)
      505 cells/uL (29%), and 89% male. Total MO (r=-0.23, p=0.006) and classical and
      non-classical MO subsets correlated negatively with CD4 percent. No correlations
      were seen with CD4 count as absolute values. Log-total MO and log-classical MO
      predicted HOMA-IR independently of HIV immuno-virologic and diabetes risk factors
      (beta=0.42, p=0.02 and beta=0.35, p=0.02, respectively) and were increased in
      subjects with metabolic syndrome (p=0.03 and p=0.05 respectively). Total and/or
      subset MO levels correlated with multiple soluble plasma biomarkers including
      CRP, IL-6, MMP-9, MPO, SAA, SAP and tPAI-1, with tPAI-1 independently predicting
      HOMA-IR (beta=0.74, p<0.001). CONCLUSIONS: MO levels increase with worsening HIV
      immune dysregulation as assessed by CD4 percent. CD4 percent may provide
      additional information about MO and metabolic risk in this population beyond
      absolute values. MO, and specifically classical MO, may contribute to insulin
      resistance and metabolic syndrome during chronic HIV infection. Multiple soluble
      plasma biomarkers including tPAI-1 increase with increase in MO. Levels of tPAI-1
      independently predict the development of insulin resistance.

PMID- 24587329
TI  - Inhibition of hepatitis C virus infection by DNA aptamer against NS2 protein.
AB  - NS2 protein is essential for hepatitis C virus (HCV) replication. NS2 protein was
      expressed and purified. Aptamers against NS2 protein were raised and antiviral
      effects of the aptamers were examined. The molecular mechanism through which the
      aptamers exert their anti-HCV activity was investigated. The data showed that
      aptamer NS2-3 inhibited HCV RNA replication in replicon cell line and infectious
      HCV cell culture system. NS2-3 and another aptamer NS2-2 were demonstrated to
      inhibit infectious virus production without cytotoxicity in vitro. They did not
      affect hepatitis B virus replication. Interferon beta (IFN-beta) and interferon
      stimulated genes (ISGs) were not induced by the aptamers in HCV-infected
      hepatocytes. Furthermore, our study showed that N-terminal region of NS2 protein
      is involved in the inhibition of HCV infection by NS2-2. I861T within NS2 is the
      major resistance mutation identified. Aptamer NS2-2 disrupts the interaction of
      NS2 with NS5A protein. The data suggest that NS2-2 aptamer against NS2 protein
      exerts its antiviral effects through binding to the N-terminal of NS2 and
      disrupting the interaction of NS2 with NS5A protein. NS2-specific aptamer is the
      first NS2 inhibitor and can be used to understand the mechanisms of virus
      replication and assembly. It may be served as attractive candidates for inclusion
      in the future HCV direct-acting antiviral combination therapies. 

PMID- 24587330
TI  - Silencing of miR-34a attenuates cardiac dysfunction in a setting of moderate, but
      not severe, hypertrophic cardiomyopathy.
AB  - Therapeutic inhibition of the miR-34 family (miR-34a,-b,-c), or miR-34a alone,
      have emerged as promising strategies for the treatment of cardiac pathology.
      However, before advancing these approaches further for potential entry into the
      clinic, a more comprehensive assessment of the therapeutic potential of
      inhibiting miR-34a is required for two key reasons. First, miR-34a has ~40% fewer
      predicted targets than the miR-34 family. Hence, in cardiac stress settings in
      which inhibition of miR-34a provides adequate protection, this approach is likely
      to result in less potential off-target effects. Secondly, silencing of miR-34a
      alone may be insufficient in settings of established cardiac pathology. We
      recently demonstrated that inhibition of the miR-34 family, but not miR-34a
      alone, provided benefit in a chronic model of myocardial infarction. Inhibition
      of miR-34 also attenuated cardiac remodeling and improved heart function
      following pressure overload, however, silencing of miR-34a alone was not
      examined. The aim of this study was to assess whether inhibition of miR-34a could
      attenuate cardiac remodeling in a mouse model with pre-existing pathological
      hypertrophy. Mice were subjected to pressure overload via constriction of the
      transverse aorta for four weeks and echocardiography was performed to confirm
      left ventricular hypertrophy and systolic dysfunction. After four weeks of
      pressure overload (before treatment), two distinct groups of animals became
      apparent: (1) mice with moderate pathology (fractional shortening decreased ~20%)
      and (2) mice with severe pathology (fractional shortening decreased ~37%). Mice
      were administered locked nucleic acid (LNA)-antimiR-34a or LNA-control with an
      eight week follow-up. Inhibition of miR-34a in mice with moderate cardiac
      pathology attenuated atrial enlargement and maintained cardiac function, but had
      no significant effect on fetal gene expression or cardiac fibrosis. Inhibition of
      miR-34a in mice with severe pathology provided no therapeutic benefit. Thus,
      therapies that inhibit miR-34a alone may have limited potential in settings of
      established cardiac pathology. 

PMID- 24587331
TI  - Development of pre-clinical models for evaluating the therapeutic potential of
      candidate siRNA targeting STAT6.
AB  - Developing siRNA therapeutics poses technical challenges including appropriate
      molecular design and testing in suitable pre-clinical models. We previously
      detailed sequence-selection and modification strategies for siRNA candidates
      targeting STAT6. Here, we describe methodology that evaluates the suitability of
      candidate siRNA for respiratory administration. Chemically-modified siRNA
      exhibited similar inhibitory activity (IC50) against STAT6 in vitro compared to
      unmodified siRNA and apical exposure testing with Caco-2 cell monolayers showed
      modification was not associated with cellular toxicity. Use of a modified RNA
      extraction protocol improved the sensitivity of a PCR-based bio-analytical assay
      (lower limit of siRNA strand quantification  =  0.01 pg/ul) which was used to
      demonstrate that lung distribution profiles for both siRNAs were similar
      following intra-tracheal administration. However, after 6 hours, modified siRNA
      was detected in lung tissue at concentrations >1000-fold higher than unmodified
      siRNA. Evaluation in a rat model of allergic inflammation confirmed the
      persistence of modified siRNA in vivo, which was detectable in broncho-alveolar
      lavage (BAL) fluid, BAL cells and lung tissue samples, 72 hours after dosing.
      Based upon the concept of respiratory allergy as a single airway disease, we
      considered nasal delivery as a route for respiratory targeting, evaluating an
      intra-nasal exposure model that involved simple dosing followed by fine
      dissection of the nasal cavity. Notably, endogenous STAT6 expression was
      invariant throughout the nasal cavities and modified siRNA persisted for at least
      3 days after administration. Coupled with our previous findings showing
      upregulated expression of inflammatory markers in nasal samples from asthmatics,
      these findings support the potential of intranasal siRNA delivery. In summary, we
      demonstrate the successful chemical modification of STAT6 targeting siRNA, which
      enhanced bio-availability without cellular toxicity or reduced efficacy. We have
      established a robust, sensitive method for determining siRNA bio-distribution in
      vivo, and developed a nasal model to aid evaluation. Further work is warranted. 

PMID- 24587332
TI  - Reduced L-carnitine transport in aortic endothelial cells from spontaneously
      hypertensive rats.
AB  - Impaired L-carnitine uptake correlates with higher blood pressure in adult men,
      and L-carnitine restores endothelial function in aortic rings from spontaneously
      hypertensive rat (SHR). Thus, endothelial dysfunction in hypertension could
      result from lower L-carnitine transport in this cell type. L-Carnitine transport
      is mainly mediated by novel organic cation transporters 1 (Octn1, Na(+)
      independent) and 2 (Octn2, Na(+)-dependent); however, their kinetic properties
      and potential consequences in hypertension are unknown. We hypothesize that L
      carnitine transport kinetic properties will be altered in aortic endothelium from
      spontaneously hypertensive rats (SHR). L-Carnitine transport was measured at
      different extracellular pH (pHo 5.5-8.5) in the absence or presence of sodium in
      rat aortic endothelial cells (RAECs) from non-hypertensive Wistar-Kyoto (WKY)
      rats and SHR. Octn1 and Octn2 mRNA relative expression was also determined.
      Dilation of endothelium-intact or denuded aortic rings in response to calcitonine
      gene related peptide (CGRP, 0.1-100 nmol/L) was measured (myography) in the
      absence or presence of L-carnitine. Total L-carnitine transport was lower in
      cells from SHR compared with WKY rats, an effect due to reduced Na(+)-dependent
      (Na(+) dep ) compared with Na(+)-independent (Na(+) indep ) transport components.
      Saturable L-carnitine transport kinetics show maximal velocity (V max), without
      changes in apparent K m for Na(+) indep transport in SHR compared with WKY rats.
      Total and Na(+) dep component of transport were increased, but Na(+) indep
      transport was reduced by extracellular alkalization in WKY rats. However,
      alkalization reduced total and Na(+) indep transport in cells from SHR. Octn2
      mRNA was higher than Octn-1 mRNA expression in cells from both conditions.
      Dilation of artery rings in response to CGRP was reduced in vessels from SHR
      compared with WKY rats. CGRP effect was endothelium-dependent and restored by L
      carnitine. All together these results suggest that reduced L-carnitine transport
      (likely via Na(+)-dependent Octn2) could limit this compound's potential
      beneficial effects in RAECs from SHR. 

PMID- 24587333
TI  - In site bioimaging of hydrogen sulfide uncovers its pivotal role in regulating
      nitric oxide-induced lateral root formation.
AB  - Hydrogen sulfide (H2S) is an important gasotransmitter in mammals. Despite
      physiological changes induced by exogenous H2S donor NaHS to plants, whether and
      how H2S works as a true cellular signal in plants need to be examined. A self
      developed specific fluorescent probe (WSP-1) was applied to track endogenous H2S
      in tomato (Solanum lycopersicum) roots in site. Bioimaging combined with
      pharmacological and biochemical approaches were used to investigate the cross
      talk among H2S, nitric oxide (NO), and Ca(2+) in regulating lateral root
      formation. Endogenous H2S accumulation was clearly associated with primordium
      initiation and lateral root emergence. NO donor SNP stimulated the generation of
      endogenous H2S and the expression of the gene coding for the enzyme responsible
      for endogenous H2S synthesis. Scavenging H2S or inhibiting H2S synthesis
      partially blocked SNP-induced lateral root formation and the expression of
      lateral root-related genes. The stimulatory effect of SNP on Ca(2+) accumulation
      and CaM1 (calmodulin 1) expression could be abolished by inhibiting H2S
      synthesis. Ca(2+) chelator or Ca(2+) channel blocker attenuated NaHS-induced
      lateral root formation. Our study confirmed the role of H2S as a cellular signal
      in plants being a mediator between NO and Ca(2+) in regulating lateral root
      formation. 

PMID- 24587334
TI  - Protein tyrosine phosphatase-1B modulates pancreatic beta-cell mass.
AB  - Protein tyrosine phosphatase 1B (PTP1B) is a negative regulator of the insulin
      signalling pathway. It has been demonstrated that PTP1B deletion protects against
      the development of obesity and Type 2 Diabetes, mainly through its action on
      peripheral tissues. However, little attention has been paid to the role of PTP1B
      in beta-cells. Therefore, our aim was to study the role of PTP1B in pancreatic
      beta-cells. Silencing of PTP1B expression in a pancreatic beta-cell line (MIN6
      cells) reveals the significance of this endoplasmic reticulum bound phosphatase
      in the regulation of cell proliferation and apoptosis. Furthermore, the ablation
      of PTP1B is able to regulate key proteins involved in the proliferation and/or
      apoptosis pathways, such as STAT3, AKT, ERK1/2 and p53 in isolated islets from
      PTP1B knockout (PTP1B (-)/(-)) mice. Morphometric analysis of pancreatic islets
      from PTP1B (-)/(-) mice showed a higher beta-cell area, concomitantly with higher
      beta-cell proliferation and a lower beta-cell apoptosis when compared to islets
      from their respective wild type (WT) littermates. At a functional level, isolated
      islets from 8 weeks old PTP1B (-)/(-) mice exhibit enhanced glucose-stimulated
      insulin secretion. Moreover, PTP1B (-)/(-) mice were able to partially reverse
      streptozotocin-induced beta-cell loss. Together, our data highlight for the first
      time the involvement of PTP1B in beta-cell physiology, reinforcing the potential
      of this phosphatase as a therapeutical target for the treatment of beta-cell
      failure, a central aspect in the pathogenesis of Type 2 Diabetes. 

PMID- 24587336
TI  - Systematic analysis of a xenograft mice model for KSHV+ primary effusion lymphoma
      (PEL).
AB  - Kaposi's sarcoma-associated herpesvirus is the causative agent of primary
      effusion lymphoma (PEL), which arises preferentially in the setting of infection
      with human immunodeficiency virus (HIV). Even with standard cytotoxic
      chemotherapy, PEL continues to cause high mortality rates, requiring the
      development of novel therapeutic strategies. PEL xenograft models employing
      immunodeficient mice have been used to study the in vivo effects of a variety of
      therapeutic approaches. However, it remains unclear whether these xenograft
      models entirely reflect clinical presentations of KSHV(+) PEL, especially given
      the recent description of extracavitary solid tumor variants arising in patients.
      In addition, effusion and solid tumor cells propagated in vivo exhibit unique
      biology, differing from one another or from their parental cell lines propagated
      through in vitro culture. Therefore, we used a KSHV(+) PEL/BCBL-1 xenograft model
      involving non-obese diabetic/severe-combined immunodeficient (NOD/SCID) mice, and
      compared characteristics of effusion and solid tumors with their parent cell
      culture-derived counterparts. Our results indicate that although this xenograft
      model can be used for study of effusion and solid lymphoma observed in patients,
      tumor cells in vivo display unique features to those passed in vitro, including
      viral lytic gene expression profile, rate of solid tumor development, the host
      proteins and the complex of tumor microenvironment. These items should be
      carefully considered when the xenograft model is used for testing novel
      therapeutic strategies against KSHV-related lymphoma. 

PMID- 24587335
TI  - TASSEL-GBS: a high capacity genotyping by sequencing analysis pipeline.
AB  - Genotyping by sequencing (GBS) is a next generation sequencing based method that
      takes advantage of reduced representation to enable high throughput genotyping of
      large numbers of individuals at a large number of SNP markers. The relatively
      straightforward, robust, and cost-effective GBS protocol is currently being
      applied in numerous species by a large number of researchers. Herein we describe
      a bioinformatics pipeline, TASSEL-GBS, designed for the efficient processing of
      raw GBS sequence data into SNP genotypes. The TASSEL-GBS pipeline successfully
      fulfills the following key design criteria: (1) Ability to run on the modest
      computing resources that are typically available to small breeding or ecological
      research programs, including desktop or laptop machines with only 8-16 GB of RAM,
      (2) Scalability from small to extremely large studies, where hundreds of
      thousands or even millions of SNPs can be scored in up to 100,000 individuals
      (e.g., for large breeding programs or genetic surveys), and (3) Applicability in
      an accelerated breeding context, requiring rapid turnover from tissue collection
      to genotypes. Although a reference genome is required, the pipeline can also be
      run with an unfinished "pseudo-reference" consisting of numerous contigs. We
      describe the TASSEL-GBS pipeline in detail and benchmark it based upon a large
      scale, species wide analysis in maize (Zea mays), where the average error rate
      was reduced to 0.0042 through application of population genetic-based SNP
      filters. Overall, the GBS assay and the TASSEL-GBS pipeline provide robust tools
      for studying genomic diversity.

PMID- 24587337
TI  - Effects of whole grain, fish and bilberries on serum metabolic profile and lipid
      transfer protein activities: a randomized trial (Sysdimet).
AB  - OBJECTIVE: We studied the combined effects of wholegrain, fish and bilberries on
      serum metabolic profile and lipid transfer protein activities in subjects with
      the metabolic syndrome. METHODS: Altogether 131 subjects (40-70 y, BMI 26-39
      kg/m(2)) with impaired glucose metabolism and features of the metabolic syndrome
      were randomized into three groups with 12-week periods according to a parallel
      study design. They consumed either: a) wholegrain and low postprandial insulin
      response grain products, fatty fish 3 times a week, and bilberries 3 portions per
      day (HealthyDiet), b) wholegrain and low postprandial insulin response grain
      products (WGED), or c) refined wheat breads as cereal products (Control).
      Altogether 106 subjects completed the study. Serum metabolic profile was studied
      using an NMR-based platform providing information on lipoprotein subclasses and
      lipids as well as low-molecular-weight metabolites. RESULTS: There were no
      significant differences in clinical characteristics between the groups at
      baseline or at the end of the intervention. Mixed model analyses revealed
      significant changes in lipid metabolites in the HealthyDiet group during the
      intervention compared to the Control group. All changes reflected increased
      polyunsaturation in plasma fatty acids, especially in n-3 PUFAs, while n-6 and n
      7 fatty acids decreased. According to tertiles of changes in fish intake, a
      greater increase of fish intake was associated with increased concentration of
      large HDL particles, larger average diameter of HDL particles, and increased
      concentrations of large HDL lipid components, even though total levels of HDL
      cholesterol remained stable. CONCLUSIONS: The results suggest that consumption of
      diet rich in whole grain, bilberries and especially fatty fish causes changes in
      HDL particles shifting their subclass distribution toward larger particles. These
      changes may be related to known protective functions of HDL such as reverse
      cholesterol transport and could partly explain the known protective effects of
      fish consumption against atherosclerosis. TRIAL REGISTRATION: The study was
      registered at ClinicalTrials.gov NCT00573781.

PMID- 24587338
TI  - Severity of depressive symptoms and accuracy of dietary reporting among obese
      women with major depressive disorder seeking weight loss treatment.
AB  - An elevation in symptoms of depression has previously been associated with
      greater accuracy of reported dietary intake, however this association has not
      been investigated among individuals with a diagnosis of major depressive
      disorder. The purpose of this study was to investigate reporting accuracy of
      dietary intake among a group of women with major depressive disorder in order to
      determine if reporting accuracy is similarly associated with depressive symptoms
      among depressed women. Reporting accuracy of dietary intake was calculated based
      on three 24-hour phone-delivered dietary recalls from the baseline phase of a
      randomized trial of weight loss treatment for 161 obese women with major
      depressive disorder. Regression models indicated that higher severity of
      depressive symptoms was associated with greater reporting accuracy, even when
      controlling for other factors traditionally associated with reporting accuracy
      (coefficient  =  0.01 95% CI = 0.01 - 0.02). Seventeen percent of the sample was
      classified as low energy reporters. Reporting accuracy of dietary intake
      increases along with depressive symptoms, even among individuals with major
      depressive disorder. These results suggest that any study investigating
      associations between diet quality and depression should also include an index of
      reporting accuracy of dietary intake as accuracy varies with the severity of
      depressive symptoms.

PMID- 24587339
TI  - Sphingosine kinase 1 and cancer: a systematic review and meta-analysis.
AB  - BACKGROUND: Sphingosine kinase 1 (SK1) is a key regulator of the dynamic
      ceramide/sphingosine 1-phosphate rheostat balance and important in the
      pathological cancer genesis, progression, and metastasis processes. Many studies
      have demonstrated SK1 overexpressed in various cancers, but no meta-analysis has
      evaluated the relationship between SK1 and various cancers. METHODS: We retrieved
      relevant articles from the PubMed, EBSCO, ISI, and OVID databases. A pooled odds
      ratio (OR) was used to assess the associations between SK1 expression and cancer;
      hazard ratios (HR) were used for 5-year and overall survival. Review Manager 5.0
      was used for the meta-analysis, and publication bias was evaluated with STATA
      12.0 (Egger's test). RESULTS: Thirty-four eligible studies (n=4,673 patients)
      were identified. SK1 positivity and high expression were significantly different
      between cancer, non-cancer, and benign tissues. SK1 mRNA and protein expression
      levels were elevated in the cancer tissues, compared with the normal tissues. SK1
      positivity rates differed between various cancer types (lowest [27.3%] in
      estrogen receptor-positive breast cancer and highest [82.2%] in tongue squamous
      cell carcinoma). SK1 positivity and high expression were associated with 5-year
      survival; the HR was 1.86 (95% confidence interval [CI], 1.18-2.94) for breast
      cancer, 1.58 (1.08-2.31) for gastric cancer, and 2.68 (2.10-3.44) for other
      cancers; the total cancer HR was 2.21 (95% CI, 1.83-2.67; P < 0.00001). The
      overall survival HRs were 2.09 (95% CI, 1.35-3.22), 1.56 (1.08-2.25), and 2.62
      (2.05-3.35) in breast, gastric, and other cancers, respectively. The total effect
      HR was 2.21 (95% CI, 1.83-2.66; P < 0.00001). CONCLUSIONS: SK1 positivity and
      high expression were significantly associated with cancer and a shorter 5-year
      and overall survival. SK1 positivity rates vary tremendously among the cancer
      types. It is necessary to further explore whether SK1 might be a predictive
      biomarker of outcomes in cancer patients.

PMID- 24587340
TI  - Complex chemosensory control of female reproductive behaviors.
AB  - Olfaction exerts a profound influence on reproductive physiology and behavior in
      many animals, including rodents. Odors are recognized by sensory neurons residing
      in the main olfactory epithelium (MOE) and the vomeronasal organ (VNO) in mice
      and many other vertebrates. The relative contributions of the MOE and VNO in the
      display of female behaviors are not well understood. Mice null for Cnga2 or Trpc2
      essentially lack odor-evoked activity in the MOE and VNO, respectively. Using
      females mutant for one or both of Cnga2 and Trpc2, we find that maternal care is
      differentially regulated by the MOE and VNO: retrieval of wandering pups requires
      the MOE and is regulated redundantly by the VNO whereas maternal aggression
      requires both sensory epithelia to be functional. Female sexual receptivity
      appears to be regulated by both the MOE and VNO. Trpc2 null females have
      previously been shown to display male-type mounting towards other males.
      Remarkably, we find that females double mutant for Cnga2 and Trpc2 continue to
      mount other males, indicating that the disinhibition of male-type sexual displays
      observed in Trpc2 null females does not require chemosensory input from a
      functional MOE. Taken together, our findings reveal a previously unappreciated
      complexity in the chemosensory control of reproductive behaviors in the female
      mouse. 

PMID- 24587341
TI  - Assessing the impact of deforestation of the Atlantic rainforest on ant-fruit
      interactions: a field experiment using synthetic fruits.
AB  - Ants frequently interact with fleshy fruits on the ground of tropical forests.
      This interaction is regarded as mutualistic because seeds benefit from enhanced
      germination and dispersal to nutrient-rich microsites, whereas ants benefit from
      consuming the nutritious pulp/aril. Considering that the process of deforestation
      affects many attributes of the ecosystem such as species abundance and
      composition, and interspecific interactions, we asked whether the interaction
      between ants and fallen fleshy fruits in the Brazilian Atlantic forest differs
      between human-created fragments and undisturbed forests. We controlled diaspore
      type and quantity by using synthetic fruits (a plastic 'seed' covered by a lipid
      rich 'pulp'), which were comparable to lipid-rich fruits. Eight independent areas
      (four undisturbed forests, and four disturbed forest fragments) were used in the
      field experiment, in which we recorded the attracted ant species, ant behaviour,
      and fruit removal distance. Fruits in undisturbed forest sites attracted a higher
      number of species than those in disturbed forests. Moreover, the occurrence of
      large, fruit-carrying ponerine ants (Pachycondyla, Odontomachus; 1.1 to 1.4 cm)
      was higher in undisturbed forests. Large species (>=3 mm) of Pheidole
      (Myrmicinae), also able to remove fruits, did not differ between forest types.
      Following these changes in species occurrence, fruit displacement was more
      frequent in undisturbed than in disturbed forests. Moreover, displacement
      distances were also greater in the undisturbed forests. Our data suggest that
      fallen fleshy fruits interacting with ants face different fates depending on the
      conservation status of the forest. Together with the severe loss of their primary
      dispersers in human-disturbed tropical forest sites, vertebrate-dispersed fruits
      may also be deprived of potential ant-derived benefits in these habitats due to
      shifts in the composition of interacting ant species. Our data illustrate the use
      of synthetic fruits to better understand the ecology of ant-fruit interactions in
      variable ecological settings, including human-disturbed landscapes. 

PMID- 24587342
TI  - FRA2 is a STAT5 target gene regulated by IL-2 in human CD4 T cells.
AB  - Signal transducers and activators of transcription 5(STAT5) are cytokine induced
      signaling proteins, which regulate key immunological processes, such as tolerance
      induction, maintenance of homeostasis, and CD4 T-effector cell differentiation.
      In this study, transcriptional targets of STAT5 in CD4 T cells were studied by
      Chromatin Immunoprecipitation (ChIP). Genomic mapping of the sites cloned and
      identified in this study revealed the striking observation that the majority of
      STAT5-binding sites mapped to intergenic (>50 kb upstream) or intronic, rather
      than promoter proximal regions. Of the 105 STAT5 responsive binding sites
      identified, 94% contained the canonical (IFN-gamma activation site) GAS motifs. A
      number of putative target genes identified here are associated with tumor
      biology. Here, we identified Fos-related antigen 2 (FRA2) as a transcriptional
      target of IL-2 regulated STAT5. FRA2 is a basic -leucine zipper (bZIP) motif
      'Fos' family transcription factor that is part of the AP-1 transcription factor
      complex and is also known to play a critical role in the progression of human
      tumours and more recently as a determinant of T cell plasticity. The binding site
      mapped to an internal intron within the FRA2 gene. The epigenetic architecture of
      FRA2, characterizes a transcriptionally active promoter as indicated by
      enrichment for histone methylation marks H3K4me1, H3K4me2, H3K4me3, and
      transcription/elongation associated marks H2BK5me1 and H4K20me1. FRA2 is
      regulated by IL-2 in activated CD4 T cells. Consistently, STAT5 bound to GAS
      sequence in the internal intron of FRA2 and reporter gene assays confirmed IL-2
      induced STAT5 binding and transcriptional activation. Furthermore, addition of
      JAK3 inhibitor (R333) or Daclizumab inhibited the induction in TCR stimulated
      cells. Taken together, our data suggest that FRA2 is a novel STAT5 target gene,
      regulated by IL-2 in activated CD4 T cells. 

PMID- 24587343
TI  - An mDia2/ROCK signaling axis regulates invasive egress from epithelial ovarian
      cancer spheroids.
AB  - Multi-cellular spheroids are enriched in ascites of epithelial ovarian cancer
      (OvCa) patients. They represent an invasive and chemoresistant cellular
      population fundamental to metastatic dissemination. The molecular mechanisms
      triggering single cell invasive egress from spheroids remain enigmatic. mDia
      formins are Rho GTPase effectors that are key regulators of F-actin cytoskeletal
      dynamics. We hypothesized that mDia2-driven F-actin dynamics promote single cell
      invasive transitions in clinically relevant three-dimensional (3D) OvCa
      spheroids. The current study is a dissection of the contribution of the F-actin
      assembly factor mDia2 formin in invasive transitions and using a clinically
      relevant ovarian cancer spheroid model. We show that RhoA-directed mDia2 activity
      is required for tight spheroid organization, and enrichment of mDia2 in the
      invasive cellular protrusions of collagen-embedded OVCA429 spheroids. Depleting
      mDia2 in ES-2 spheroids enhanced invasive dissemination of single amoeboid-shaped
      cells. This contrasts with spheroids treated with control siRNA, where a
      mesenchymal invasion program predominated. Inhibition of another RhoA effector,
      ROCK, had no impact on ES-2 spheroid formation but dramatically inhibited
      spheroid invasion through induction of a highly elongated morphology. Concurrent
      inhibition of ROCK and mDia2 blocked single cell invasion from ES-2 spheroids
      more effectively than inhibition of either protein alone, indicating that
      invasive egress of amoeboid cells from mDia2-depleted spheroids is ROCK
      dependent. Our findings indicate that multiple GTPase effectors must be
      suppressed in order to fully block invasive egress from ovarian cancer spheroids.
      Furthermore, tightly regulated interplay between ROCK and mDia2 signaling
      pathways dictates the invasive capacities and the type of invasion program
      utilized by motile spheroid-derived ovarian cancer cells. As loss of the gene
      encoding mDia2, DRF3, has been linked to cancer progression and metastasis, our
      results set the stage for understanding molecular mechanisms involved in mDia2
      dependent egress of invasive cells from primary epithelial tumors.

PMID- 24587344
TI  - Quantitative magnetic resonance imaging in limb-girdle muscular dystrophy 2I: a
      multinational cross-sectional study.
AB  - We conducted a prospective multinational study of muscle pathology using magnetic
      resonance imaging (MRI) in patients with limb-girdle muscular dystrophy 2I
      (LGMD2I). Thirty eight adult ambulant LGMD2I patients (19 male; 19 female) with
      genetically identical mutations (c.826C>A) in the fukutin-related protein (FKRP)
      gene were recruited. In each patient, T1-weighted (T1w) imaging was assessed by
      qualitative grading for 15 individual lower limb muscles and quantitative Dixon
      imaging was analysed on 14 individual lower limb muscles by region of interest
      analysis. We described the pattern and appearance of muscle pathology and gender
      differences, not previously reported for LGMD2I. Diffuse fat infiltration of the
      gastrocnemii muscles was demonstrated in females, whereas in males fat
      infiltration was more prominent in the medial than the lateral gastrocnemius (p =
      0.05). In the anterior thigh of males, in contrast to females, median fat
      infiltration in the vastus medialis muscle (45.7%) exceeded that in the vastus
      lateralis muscle (11.2%) (p<0.005). MRI is non-invasive, objective and does not
      rely on patient effort compared to clinical and physical measures that are
      currently employed. We demonstrated (i) that the quantitative Dixon technique is
      an objective quantitative marker of disease and (ii) new observations of gender
      specific patterns of muscle involvement in LGMD2I.

PMID- 24587345
TI  - Rab5 isoforms orchestrate a "division of labor" in the endocytic network; Rab5C
      modulates Rac-mediated cell motility.
AB  - Rab5, the prototypical Rab GTPase and master regulator of the endocytic pathway,
      is encoded as three differentially expressed isoforms, Rab5A, Rab5B and Rab5C.
      Here, we examined the differential effects of Rab5 isoform silencing on cell
      motility and report that Rab5C, but neither Rab5A nor Rab5B, is selectively
      associated with the growth factor-activation of Rac1 and with enhanced cell
      motility. Initial observations revealed that silencing of Rab5C expression, but
      neither Rab5A nor Rab5C, led to spindle-shaped cells that displayed reduced
      formation of membrane ruffles. When subjected to a scratch wound assay, cells
      depleted of Rab5C, but not Rab5A or Rab5B, demonstrated reduced cell migration.
      U937 cells depleted of Rab5C also displayed reduced cell motility in a Transwell
      plate migration assay. To examine activation of Rac, HeLa cells stably expressing
      GFP-Rac1 were independently depleted of Rab5A, Rab5B or Rab5C and seeded onto
      coverslips imprinted with a crossbow pattern. 3-D GFP-Rac1 images of micro
      patterned cells show that GFP-Rac1 was less localized to the cell periphery in
      the absence of Rab5C. To confirm the connection between Rab5C and Rac activation,
      HeLa cells depleted of Rab5 isoforms were starved and then stimulated with EGF.
      Rac1 pull-down assays revealed that EGF-stimulated Rac1 activity was
      significantly suppressed in Rab5C-suppressed cells. To determine whether events
      upstream of Rac activation were affected by Rab5C, we observed that EGF
      stimulated Akt phosphorylation was suppressed in cells depleted of Rab5C.
      Finally, since spatio-temporal assembly/disassembly of adhesion complexes are
      essential components of cell migration, we examined the effect of Rab5 isoform
      depletion on the formation of focal adhesion complexes. Rab5C-depleted HeLa cells
      have significantly fewer focal adhesion foci, in accordance with the lack of
      persistent lamellipodial protrusions and reduced directional migration. We
      conclude that Rab5 isoforms selectively oversee the multiple signaling and
      trafficking events associated with the endocytic network. 

PMID- 24587346
TI  - On the formation of lipid droplets in human adipocytes: the organization of the
      perilipin-vimentin cortex.
AB  - We report on the heterogeneity and diversity of lipid droplets (LDs) in early
      stages of adipogenesis by elucidating the cell and molecular biology of
      amphiphilic and cytoskeletal proteins regulating and stabilizing the generation
      of LDs in human adipose cells. A plethora of distinct and differently sized LDs
      was detected by a brief application of adipocyte differentiation medium and
      additional short treatment with oleic acid. Using these cells and highly specific
      antibodies for LD-binding proteins of the perilipin (PLIN) family, we could
      distinguish between endogenously derived LDs (endogenous LDs) positive for
      perilipin from exogenously induced LDs (exogenous LDs) positive for adipophilin,
      TIP47 and S3-12. Having optimized these stimulation conditions, we used early
      adipogenic differentiation stages to investigate small-sized LDs and concentrated
      on LD-protein associations with the intermediate-sized filament (IF) vimentin.
      This IF protein was described earlier to surround lipid globules, showing
      spherical, cage-like structures. Consequently - by biochemical methods, by
      immunofluorescence microscopy and by electron- and immunoelectron microscopy -
      various stages of emerging lipid globules were revealed with perilipin as linking
      protein between LDs and vimentin. For this LD-PLIN-Vimentin connection, a model
      is now proposed, suggesting an interaction of proteins via opposed charged amino
      acid domains respectively. In addition, multiple sheaths of smooth endoplasmic
      reticulum cisternae surrounding concentrically nascent LDs are shown. Based on
      our comprehensive localization studies we present and discuss a novel pathway for
      the LD formation. 

PMID- 24587347
TI  - JNK contributes to the tumorigenic potential of human cholangiocarcinoma cells
      through the mTOR pathway regulated GRP78 induction.
AB  - Less is known about the roles of c-Jun N-terminal kinase (JNK) in
      cholangiocarcinoma (CCA). Here, we report that JNK exerts its oncogenic action in
      human CCA cells, partially due to the mammalian target of rapamycin (mTOR)
      pathway regulated glucose-regulated protein 78 (GRP78) induction. In human CCA
      cells, the phosphorylation of eukaryotic initiation factor alpha (eIF2alpha)
      results in the accumulation of activating transcription factor 4 (ATF4) and GRP78
      independent of unfolded protein response (UPR). Suppression of GRP78 expression
      decreases the proliferation and invasion of human CCA cells. It's notable that
      mTOR is required for eIF2alpha phosphorylation-induced ATF4 and GRP78 expression.
      Importantly, JNK promotes eIF2alpha/ATF4-mediated GRP78 induction through
      regulating the activity of mTOR. Thus, our study implicates JNK/mTOR signaling
      plays an important role in cholangiocarcinogenesis, partially through promoting
      the eIF2alpha/ATF4/GRP78 pathway. 

PMID- 24587348
TI  - Copy number variations burden on miRNA genes reveals layers of complexities
      involved in the regulation of pathways and phenotypic expression.
AB  - MicroRNAs are involved in post-transcriptional down-regulation of gene
      expression. Variations in miRNA genes can severely affect downstream-regulated
      genes and their pathways. However, population-specific burden of CNVs on miRNA
      genes and the complexities created towards the phenotype is not known. From a
      total of 44109 CNVs investigated from 1715 individuals across 12 populations
      using high-throughput arrays, 4007 miRNA-CNVs (~ 9%) consisting 6542 (~ 5%) miRNA
      genes with a total of 333 (~ 5%) singleton miRNA genes were identified. We found
      miRNA-CNVs across the genomes of individuals showing multiple hits in many
      targets, co-regulated under the same pathway. This study proposes four mechanisms
      unraveling the many complexities in miRNA genes, targets and co-regulated miRNA
      genes towards establishment of phenotypic diversity.

PMID- 24587349
TI  - Optimization and in vivo toxicity evaluation of G4.5 PAMAM dendrimer-risperidone
      complexes.
AB  - Risperidone is an approved antipsychotic drug belonging to the chemical class of
      benzisoxazole. This drug has low solubility in aqueous medium and poor
      bioavailability due to extensive first-pass metabolism and high protein binding
      (>90%). Since new strategies to improve efficient treatments are needed, we
      studied the efficiency of anionic G4.5 PAMAM dendrimers as nanocarriers for this
      therapeutic drug. To this end, we explored dendrimer-risperidone complexation
      dependence on solvent concentration, pH and molar relationship. The best
      dendrimer-risperidone incorporation (46 risperidone molecules per dendrimer) was
      achieved with a mixture of chloroform:methanol 50?50 v/v solution pH 3. In
      addition, to explore the possible effects of this complex, in vivo studies were
      carried out in the zebrafish model. Changes in the development of dopaminergic
      neurons and motoneurons were studied using tyrosine hydroxylase and calretinin,
      respectively. Physiological changes were studied through histological sections
      stained with hematoxylin-eosin to observe possible morphological brain changes.
      The most significant changes were observed when larvae were treated with free
      risperidone, and no changes were observed when larvae were treated with the
      complex. 

PMID- 24587350
TI  - Learning from host-defense peptides: cationic, amphipathic peptoids with potent
      anticancer activity.
AB  - Cationic, amphipathic host defense peptides represent a promising group of agents
      to be developed for anticancer applications. Poly-N-substituted glycines, or
      peptoids, are a class of biostable, peptidomimetic scaffold that can display a
      great diversity of side chains in highly tunable sequences via facile solid-phase
      synthesis. Herein, we present a library of anti-proliferative peptoids that
      mimics the cationic, amphipathic structural feature of the host defense peptides
      and explore the relationships between the structure, anticancer activity and
      selectivity of these peptoids. Several peptoids are found to be potent against a
      broad range of cancer cell lines at low-micromolar concentrations including
      cancer cells with multidrug resistance (MDR), causing cytotoxicity in a
      concentration-dependent manner. They can penetrate into cells, but their
      cytotoxicity primarily involves plasma membrane perturbations. Furthermore,
      peptoid 1, the most potent peptoid synthesized, significantly inhibited tumor
      growth in a human breast cancer xenotransplantation model without any noticeable
      acute adverse effects in mice. Taken together, our work provided important
      structural information for designing host defense peptides or their mimics for
      anticancer applications. Several cationic, amphipathic peptoids are very
      attractive for further development due to their high solubility, stability
      against protease degradation, their broad, potent cytotoxicity against cancer
      cells and their ability to overcome multidrug resistance. 

PMID- 24587352
TI  - Bacterial antagonists of fungal pathogens also control root-knot nematodes by
      induced systemic resistance of tomato plants.
AB  - The potential of bacterial antagonists of fungal pathogens to control the root
      knot nematode Meloidogyne incognita was investigated under greenhouse conditions.
      Treatment of tomato seeds with several strains significantly reduced the numbers
      of galls and egg masses compared with the untreated control. Best performed
      Bacillus subtilis isolates Sb4-23, Mc5-Re2, and Mc2-Re2, which were further
      studied for their mode of action with regard to direct effects by bacterial
      metabolites or repellents, and plant mediated effects. Drenching of soil with
      culture supernatants significantly reduced the number of egg masses produced by
      M. incognita on tomato by up to 62% compared to the control without culture
      supernatant. Repellence of juveniles by the antagonists was shown in a linked
      twin-pot set-up, where a majority of juveniles penetrated roots on the side
      without inoculated antagonists. All tested biocontrol strains induced systemic
      resistance against M. incognita in tomato, as revealed in a split-root system
      where the bacteria and the nematodes were inoculated at spatially separated roots
      of the same plant. This reduced the production of egg masses by up to 51%, while
      inoculation of bacteria and nematodes in the same pot had only a minor additive
      effect on suppression of M. incognita compared to induced systemic resistance
      alone. Therefore, the plant mediated effect was the major reason for antagonism
      rather than direct mechanisms. In conclusion, the bacteria known for their
      antagonistic potential against fungal pathogens also suppressed M. incognita.
      Such "multi-purpose" bacteria might provide new options for control strategies,
      especially with respect to nematode-fungus disease complexes that cause
      synergistic yield losses. 

PMID- 24587351
TI  - Human and mouse skeletal muscle stem cells: convergent and divergent mechanisms
      of myogenesis.
AB  - Satellite cells are the chief contributor to skeletal muscle growth and
      regeneration. The study of mouse satellite cells has accelerated in recent years
      due to technical advancements in the isolation of these cells. The study of human
      satellite cells has lagged and thus little is known about how the biology of
      mouse and human satellite cells compare. We developed a flow cytometry-based
      method to prospectively isolate human skeletal muscle progenitors from the
      satellite cell pool using positive and negative selection markers. Results show
      that this pool is enriched in PAX7 expressing cells that possess robust myogenic
      potential including the ability to give rise to de novo muscle in vivo. We
      compared mouse and human satellite cells in culture and identify differences in
      the elaboration of the myogenic genetic program and in the sensitivity of the
      cells to cytokine stimulation. These results indicate that not all mechanisms
      regulating mouse satellite cell activation are conserved in human satellite cells
      and that such differences may impact the clinical translation of therapeutics
      validated in mouse models. Thus, the findings of this study are relevant to
      developing therapies to combat muscle disease. 

PMID- 24587353
TI  - Benchmarking successional progress in a quantitative food web.
AB  - Central to ecology and ecosystem management, succession theory aims to
      mechanistically explain and predict the assembly and development of ecological
      communities. Yet processes at lower hierarchical levels, e.g. at the species and
      functional group level, are rarely mechanistically linked to the under
      investigated system-level processes which drive changes in ecosystem properties
      and functioning and are comparable across ecosystems. As a model system for
      secondary succession, seasonal plankton succession during the growing season is
      readily observable and largely driven autogenically. We used a long-term dataset
      from large, deep Lake Constance comprising biomasses, auto- and heterotrophic
      production, food quality, functional diversity, and mass-balanced food webs of
      the energy and nutrient flows between functional guilds of plankton and partly
      fish. Extracting population- and system-level indices from this dataset, we
      tested current hypotheses about the directionality of successional progress which
      are rooted in ecosystem theory, the metabolic theory of ecology, quantitative
      food web theory, thermodynamics, and information theory. Our results indicate
      that successional progress in Lake Constance is quantifiable, passing through
      predictable stages. Mean body mass, functional diversity, predator-prey weight
      ratios, trophic positions, system residence times of carbon and nutrients, and
      the complexity of the energy flow patterns increased during succession. In
      contrast, both the mass-specific metabolic activity and the system export
      decreased, while the succession rate exhibited a bimodal pattern. The weighted
      connectance introduced here represents a suitable index for assessing the
      evenness and interconnectedness of energy flows during succession. Diverging from
      earlier predictions, ascendency and eco-exergy did not increase during
      succession. Linking aspects of functional diversity to metabolic theory and food
      web complexity, we reconcile previously disjoint bodies of ecological theory to
      form a complete picture of successional progress within a pelagic food web. This
      comprehensive synthesis may be used as a benchmark for quantifying successional
      progress in other ecosystems. 

PMID- 24587354
TI  - Optimizing recellularization of whole decellularized heart extracellular matrix.
AB  - RATIONALE: Perfusion decellularization of cadaveric hearts removes cells and
      generates a cell-free extracellular matrix scaffold containing acellular vascular
      conduits, which are theoretically sufficient to perfuse and support tissue
      engineered heart constructs. However, after transplantation, these acellular
      vascular conduits clot, even with anti-coagulation. Here, our objective was to
      create a less thrombogenic scaffold and improve recellularized-left ventricular
      contractility by re-lining vascular conduits of a decellularized rat heart with
      rat aortic endothelial cells (RAECs). METHODS AND RESULTS: We used three
      strategies to recellularize perfusion-decellularized rat heart vasculature with
      RAECs: retrograde aortic infusion, brachiocephalic artery (BA) infusion, or a
      combination of inferior vena cava (IVC) plus BA infusion. The re-endothelialized
      scaffolds were maintained under vascular flow in vitro for 7 days, and then cell
      morphology, location, and viability were examined. Thrombogenicity of the
      scaffold was assessed in vitro and in vivo. Both BA and IVC+BA cell delivery
      resulted in a whole heart distribution of RAECs that proliferated, retained an
      endothelial phenotype, and expressed endothelial nitric oxide synthase and von
      Willebrand factor. Infusing RAECs via the combination IVC+BA method increased
      scaffold cellularity and the number of vessels that were lined with endothelial
      cells; re-endothelialization by using BA or IVC+BA cell delivery significantly
      reduced in vitro thrombogenicity. In vivo, both acellular and re-endothelialized
      scaffolds recruited non-immune host cells into the organ parenchyma and
      vasculature. Finally, re-endothelialization before recellularization of the left
      ventricular wall with neonatal cardiac cells enhanced construct contractility.
      CONCLUSIONS: This is the first study to re-endothelialize whole decellularized
      hearts throughout both arterial and venous beds and cavities by using arterial
      and venous delivery. The combination (IVC+BA) delivery strategy results in
      enhanced scaffold vessel re-endothelialization compared to single-route
      strategies. Re-endothelialization reduced scaffold thrombogencity and improved
      contractility of left ventricular-recellularized constructs. Thus, vessel and
      cavity re-endothelialization creates superior vascularized scaffolds for use in
      whole-organ recellularization applications.

PMID- 24587355
TI  - Amphetamine fails to alter cued recollection of emotional images: study of
      encoding, retrieval, and state-dependency.
AB  - Stimulant drugs facilitate both encoding and retrieval of salient information in
      laboratory animals, but less is known about their effects on memory for
      emotionally salient visual images in humans. The current study investigated
      dextroamphetamine (AMP) effects on memory for emotional pictures in healthy
      humans, by administering the drug only at encoding, only at retrieval, or at both
      encoding and retrieval. During the encoding session, all participants viewed
      standardized positive, neutral, and negative pictures from the International
      Affective Picture System (IAPS). 48 hours later they attended a retrieval session
      testing their cued recollection of these stimuli. Participants were randomly
      assigned to one of four conditions (N=20 each): condition AP (20 mg AMP at
      encoding and placebo (PL) at retrieval); condition PA (PL at encoding and AMP at
      retrieval); condition AA (AMP at encoding and retrieval); or condition PP (PL at
      encoding and retrieval). Amphetamine produced its expected effects on
      physiological and subjective measures, and negative pictures were recollected
      more frequently than neutral pictures. However, contrary to hypotheses, AMP did
      not affect recollection for positive, negative, or neutral stimuli, whether it
      was administered at encoding, retrieval, or at both encoding and retrieval.
      Moreover, recollection accuracy was not state-dependent. Considered in light of
      other recent drug studies in humans, this study highlights the sensitivity of
      drug effects to memory testing conditions and suggests future strategies for
      translating preclinical findings to human behavioral laboratories.

PMID- 24587356
TI  - Autoreactive IgE is prevalent in systemic lupus erythematosus and is associated
      with increased disease activity and nephritis.
AB  - The presence of autoantibodies in systemic lupus erythematosus, particularly
      those of the IgG subclass, have long been associated with disease onset and
      activity. Here we explored the prevalence of autoreactive IgE in SLE and its
      relevance to disease in French (n = 79) and United States (US) (n = 117) cohorts
      with a mean age of 41.5 +/- 12.7 and 43.6 +/- 15.3 years and disease duration of
      13.5 +/- 8.5 and 16.6 +/- 11.9 years, respectively. Our findings show that
      approximately 65% of all SLE subjects studied produced IgE antibodies to the
      seven autoantigens tested. This positivity was increased to almost 83% when only
      those subjects with active disease were considered. SLE subjects who were
      positive for anti-dsDNA, -Sm, and -SSB/La -specific IgE showed a highly
      significant association in the levels of these antibodies with disease activity
      similar to that of the corresponding IgG's. A strong association of IgE
      autoantibodies with active nephritis was also found in the combined cohort
      analysis. A test of the predictive value of autoreactive IgE's and IgGs for
      disease activity (SLE Disease Activity Index (SLEDAI) >= 4) revealed that the
      best predictors were dsDNA-specific IgE and IgG, and that the age of an SLE
      subject influenced this predictive model. The finding argue that the overall
      levels of IgE autoantibodies, independently or in combination with IgG
      autoantibodies, may serve as indicators of active disease.

PMID- 24587357
TI  - Risk of acute lung injury/acute respiratory distress syndrome in critically ill
      adult patients with pre-existing diabetes: a meta-analysis.
AB  - BACKGROUND: The impact of pre-existing diabetes on the development of acute lung
      injury/acute respiratory distress syndrome (ALI/ARDS) in critically ill patients
      remains unclear. We performed a meta-analysis of cohort studies to evaluate the
      risk of ALI/ARDS in critically ill patients with and without pre-existing
      diabetes. MATERIALS AND METHODS: We searched PubMed and Embase from the inception
      to September 2013 for cohort studies assessing the effect of pre-existing
      diabetes on ALI/ARDS occurrence. Pooled odds ratio (OR) with 95% confidence
      interval (CI) was calculated using random- or fixed-effect models when
      appropriate. RESULTS: Seven cohort studies with a total of 12,794 participants
      and 2,937 cases of pre-existing diabetes, and 2,457 cases of ALI/ARDS were
      included in the meta-analysis. A fixed-effects model meta-analysis showed that
      pre-existing diabetes was associated with a reduced risk of ALI/ARDS (OR 0.66;
      95% CI, 0.55-0.80; p<0.001), with low heterogeneity among the studies
      (I(2)=18.9%; p=0.286). However, the asymmetric funnel plot and Egger's test
      (p=0.007) suggested publication bias may exist. CONCLUSIONS: Our meta-analysis
      suggests that pre-existing diabetes was associated with a decreased risk of
      ALI/ARDS in critically ill adult patients. However, the result should be
      interpreted with caution because of the potential bias and confounding in the
      included studies.

PMID- 24587358
TI  - SIRT1 gene polymorphisms affect the protein expression in cardiovascular
      diseases.
AB  - Cardiovascular disease (CVD), the leading cause of death worldwide, is related to
      gene-environment interactions due to epigenetic factors. SIRT1 protein and its
      downstream pathways are critical for both normal homeostasis and protection from
      CVD-induced defects. The aim of this study was to investigate the association
      between SIRT1 single nucleotide polymorphisms (SNPs) (rs7895833 A>G in the
      promoter region, rs7069102 C>G in intron 4 and rs2273773 C>T in exon 5 silent
      mutation) and SIRT1 and eNOS (endothelial nitric oxide synthase) protein
      expression as well as total antioxidant status (TAS), total oxidant status (TOS)
      and oxidative stress index (OSI) in CVD patients as compared to controls. The
      frequencies of mutant genotypes and alleles for rs7069102 and rs2273773 were
      significantly higher in patients with CVD compared to control group. The risk for
      CVD was increased by 2.4 times for rs7069102 and 1.9 times for rs2273773 in
      carriers of mutant allele compared with carriers of wild-type allele pointing the
      protective role of C allele for both SNPs against CVD. For rs7895833, there was
      no significant difference in genotype and allele distributions between groups.
      SIRT1 protein, TAS, TOS and OSI levels significantly increased in patients as
      compared to control group. In contrast, level of eNOS protein was considerably
      low in the CVD patients. An increase in the SIRT1 expression in the CVD patients
      carrying mutant genotype for rs7069102 and heterozygote genotype for all three
      SNPs was observed. This is the first study reporting an association between SIRT1
      gene polymorphisms and the levels of SIRT1 and eNOS expressions as well as TAS,
      TOS and OSI. 

PMID- 24587359
TI  - Predicting the development of diabetes using the product of triglycerides and
      glucose: the Chungju Metabolic Disease Cohort (CMC) study.
AB  - BACKGROUND: To determine whether the TyG index, a product of the levels of
      triglycerides and fasting plasma glucose (FPG) might be a valuable marker for
      predicting future diabetes. METHODS: A total of 5,354 nondiabetic subjects who
      had completed their follow-up visit for evaluating diabetes status were selected
      from a large cohort of middle-aged Koreans in the Chungju Metabolic Disease
      Cohort study. The risk of diabetes was assessed according to the baseline TyG
      index, calculated as ln[fasting triglycerides (mg/dL) * FPG (mg/dL)/2]. The
      median follow-up period was 4.6 years. RESULTS: During the follow-up period, 420
      subjects (7.8%) developed diabetes. The baseline values of the TyG index were
      significantly higher in these subjects compared with nondiabetic subjects (8.9 +/
      0.6 vs. 8.6 +/- 0.6; P<0.0001) and the incidence of diabetes increased in
      proportion to TyG index quartiles. After adjusting for age, gender, body mass
      index, waist circumference, systolic blood pressure, high-density lipoprotein
      (HDL)-cholesterol level, a family history of diabetes, smoking, alcohol drinking,
      education level and serum insulin level, the risk of diabetes onset was more than
      fourfold higher in the highest vs. the lowest quartile of the TyG index (relative
      risk, 4.095; 95% CI, 2.701-6.207). The predictive power of the TyG index was
      better than the triglyceride/HDL-cholesterol ratio or the homeostasis model
      assessment of insulin resistance. CONCLUSIONS: The TyG index, a simple measure
      reflecting insulin resistance, might be useful in identifying individuals at high
      risk of developing diabetes.

PMID- 24587360
TI  - Molecular characterization of HBV strains circulating among the treatment-naive
      HIV/HBV co-infected patients of eastern India.
AB  - Previously we reported that the exposure to hepatitis B virus (HBV) infection
      serves as a major threat among the treatment naive HIV infected population of
      eastern India. Hence, molecular characterization of these strains is of utmost
      importance in order to identify clinically significant HBV mutations. A total of
      85 treatment naive HIV/HBV co-infected participants were included of whom the
      complete basal core promoter/precore region, the core and the whole envelope gene
      could be successfully sequenced for 59, 57 and 39 isolates respectively.
      Following phylogenetic analysis, it was found that HBV/D was the predominant
      genotype with HBV/D2 (38.5%) being the most prevalent subgenotype followed by
      HBV/A1. The major mutations affecting HBeAg expression includes the A1762T/G1764A
      (13.6%), G1896A (22%) and G1862T mutation (33.9%) which was predominantly
      associated with HBV/A1. Moreover, the prevalence of G1896A was considerably high
      among the HBeAg negative HIV/HBV co-infected subjects compared to HBV mono
      infection. The main amino acid substitutions within the MHC class II restricted T
      cell epitope of HBcAg includes the T12S (15.8%) and T67N (12.3%) mutation and the
      V27I (10.5%) mutation in the MHC class I restricted T-cell epitope. PreS1/S2
      deletion was detected in 3 isolates with all harboring the BCP double mutation.
      Furthermore, the frequently occurring mutations in the major hydrophilic loop of
      the S gene include the T125M, A128V and M133I/L. Therefore, this study is the
      first from India to report useful information on the molecular heterogeneity of
      the HBV strains circulating among the treatment naive HIV/HBV co-infected
      population and is thus clinically relevant.

PMID- 24587362
TI  - Functional responses and resilience of boreal forest ecosystem after reduction of
      deer density.
AB  - The functional trait-based approach is increasingly used to predict responses of
      ecological communities to disturbances, but most studies target a single
      taxonomic group. Here, we assessed the resilience of a forest ecosystem to an
      overabundant herbivore population by assessing changes in 19 functional traits
      for plant, 13 traits for ground beetle and 16 traits for songbird communities
      after six years of controlled browsing on Anticosti Island (Quebec, Canada). Our
      results indicated that plants were more responsive to 6 years of reduced browsing
      pressure than ground beetles and songbirds. However, co-inertia analysis revealed
      that ground beetle communities responded in a similar way than plant communities
      with stronger relationships between plant and ground beetle traits at reduced
      deer density, a pattern not detected between plant and songbird. High deer
      density favored plants species that reproduce vegetatively and with abiotic
      pollination and seed dispersal, traits implying little interaction with animal.
      On the other hand, traits found at reduced deer density mostly involved trophic
      interaction. For example, plants in this treatment had fleshy fruits and large
      seeds dispersed by birds or other animals whereas ground beetle species were
      carnivorous. Overall, our results suggest that plant communities recovered some
      functional components to overabundant herbivore populations, since most traits
      associated with undisturbed forests were reestablished after six years of deer
      reduction. The re-establishment of functional plant communities with traits
      involving trophic interaction induces changes in the ground-beetle trait
      community, but forest structure remains likely insufficiently heterogeneous to
      shift the songbird trait community within six years. 

PMID- 24587361
TI  - Spatiotemporal expression of MANF in the developing rat brain.
AB  - Mesencephalic astrocyte-derived neurotrophic factor (MANF) is an evolutionarily
      conserved neurotrophic factor which exhibited neuroprotective properties. Recent
      studies suggested that MANF may play a role in the neural development of
      Drosophila and zebra fishes. In this study, we investigated the spatiotemporal
      expression of MANF in the brain of postnatal and adult rats. MANF expression
      appeared wide spread and mainly localized in neurons. In the cerebral cortex,
      neurons in layer IV and VI displayed particularly strong MANF immunoreactivity.
      In the hippocampus, intensive MANF expression was observed throughout the
      subfields of Cornu Amonis (CA1, CA2, and CA3) and the granular layer of the
      dentate gyrus (DG). In the substantia nigra, high MANF expression was shown in
      the substantia nigra pars compacta (SNpc). In the thalamus, the anterodorsal
      thalamic nucleus (ADTN) exhibited the highest MANF immunoreactivity. In the
      hypothalamus, intensive MANF immunoreactivity was shown in the supraoptic nucleus
      (SON) and tuberomammillary nucleus (TMN). In the cerebellum, MANF was localized
      in the external germinal layer (EGL), Purkinje cell layer (PCL), internal granule
      layer (IGL) and the deep cerebellar nuclei (DCN). We examined the developmental
      expression of MANF on postnatal day (PD) 3, 5, 7, 9, 15, 21, 30 and adulthood. In
      general, the levels of MANF were high in the early PDs (PD3 and PD5), and
      declined gradually as the brain matured; MANF expression in the adult brain was
      the lowest among all time points examined. However, in some structures, such as
      PCL, IGL, SON, TMN and locus coeruleus (LC), high expression of MANF sustained
      throughout the postnatal period and persisted into adulthood. Our results
      indicated that MANF was developmentally regulated and may play a role in the
      maturation of the central nervous system (CNS). 

PMID- 24587364
TI  - Dynamics of potassium release and adsorption on rice straw residue.
AB  - Straw application can not only increase crop yields, improve soil structure and
      enrich soil fertility, but can also enhance water and nutrient retention. The aim
      of this study was to ascertain the relationships between straw decomposition and
      the release-adsorption processes of K(+). This study increases the understanding
      of the roles played by agricultural crop residues in the soil environment,
      informs more effective straw recycling and provides a method for reducing
      potassium loss. The influence of straw decomposition on the K(+) release rate in
      paddy soil under flooded condition was studied using incubation experiments,
      which indicated the decomposition process of rice straw could be divided into two
      main stages: (a) a rapid decomposition stage from 0 to 60 d and (b) a slow
      decomposition stage from 60 to 110 d. However, the characteristics of the straw
      potassium release were different from those of the overall straw decomposition,
      as 90% of total K was released by the third day of the study. The batches of the
      K sorption experiments showed that crop residues could adsorb K(+) from the
      ambient environment, which was subject to decomposition periods and extra K(+)
      concentration. In addition, a number of materials or binding sites were observed
      on straw residues using IR analysis, indicating possible coupling sites for K(+)
      ions. The aqueous solution experiments indicated that raw straw could absorb
      water at 3.88 g g(-1), and this rate rose to its maximum 15 d after incubation.
      All of the experiments demonstrated that crop residues could absorb large amount
      of aqueous solution to preserve K(+) indirectly during the initial decomposition
      period. These crop residues could also directly adsorb K(+) via physical and
      chemical adsorption in the later period, allowing part of this K(+) to be
      absorbed by plants for the next growing season. 

PMID- 24587363
TI  - Suppression of immunodominant antitumor and antiviral CD8+ T cell responses by
      indoleamine 2,3-dioxygenase.
AB  - Indoleamine 2,3-dioxygenase (IDO) is a tryptophan-degrading enzyme known to
      suppress antitumor CD8(+) T cells (TCD8). The role of IDO in regulation of
      antiviral TCD8 responses is far less clear. In addition, whether IDO controls
      both immunodominant and subdominant TCD8 is not fully understood. This is an
      important question because the dominance status of tumor- and virus-specific TCD8
      may determine their significance in protective immunity and in vaccine design. We
      evaluated the magnitude and breadth of cross-primed TCD8 responses to simian
      virus 40 (SV40) large T antigen as well as primary and recall TCD8 responses to
      influenza A virus (IAV) in the absence or presence of IDO. IDO(-/-) mice and wild
      type mice treated with 1-methyl-D-tryptophan, a pharmacological inhibitor of IDO,
      exhibited augmented responses to immunodominant epitopes encoded by T antigen and
      IAV. IDO-mediated suppression of these responses was independent of
      CD4(+)CD25(+)FoxP3(+) regulatory T cells, which remained numerically and
      functionally intact in IDO(-/-) mice. Treatment with L-kynurenine failed to
      inhibit TCD8 responses, indicating that tryptophan metabolites are not
      responsible for the suppressive effect of IDO in our models. Immunodominant T
      antigen-specific TCD8 from IDO(-/-) mice showed increased Ki-67 expression,
      suggesting that they may have acquired a more vigorous proliferative capacity in
      vivo. In conclusion, IDO suppresses immunodominant TCD8 responses to tumor and
      viral antigens. Our work also demonstrates that systemic primary and recall TCD8
      responses to IAV are controlled by IDO. Inhibition of IDO thus represents an
      attractive adjuvant strategy in boosting anticancer and antiviral TCD8 targeting
      highly immunogenic antigens. 

PMID- 24587365
TI  - Beneficial antimicrobial effect of the addition of an aminoglycoside to a beta
      lactam antibiotic in an E. coli porcine intensive care severe sepsis model.
AB  - This study aimed to determine whether the addition of an aminoglycoside to a beta
      lactam antibiotic increases the antimicrobial effect during the early phase of
      Gram-negative severe sepsis/septic shock. A porcine model was selected that
      considered each animal's individual blood bactericidal capacity. Escherichia
      coli, susceptible to both antibiotics, was given to healthy pigs intravenously
      during 3 h. At 2 h, the animals were randomized to a 20-min infusion with either
      cefuroxime alone (n = 9), a combination of cefuroxime+tobramycin (n = 9), or
      saline (control, n = 9). Blood samples were collected hourly for cultures and
      quantitative polymerase chain reaction (PCR). Bacterial growth in the organs
      after 6 h was chosen as the primary endpoint. A blood sample was obtained at
      baseline before start of bacterial infusion for ex vivo investigation of the
      blood bactericidal capacity. At 1 h after the administration of the antibiotics,
      a second blood sample was taken for ex vivo investigation of the antibiotic
      induced blood killing activity. All animals developed severe sepsis/septic shock.
      Blood cultures and PCR rapidly became negative after completed bacterial
      infusion. Antibiotic-induced blood killing activity was significantly greater in
      the combination group than in the cefuroxime group (p<0.001). Growth of bacteria
      in the spleen was reduced in the two antibiotic groups compared with the controls
      (p<0.01); no difference was noted between the two antibiotic groups. Bacterial
      growth in the liver was significantly less in the combination group than in the
      cefuroxime group (p<0.05). High blood bactericidal capacity at baseline was
      associated with decreased growth in the blood and spleen (p<0.05). The addition
      of tobramycin to cefuroxime results in increased antibiotic-induced blood killing
      activity and less bacteria in the liver than cefuroxime alone. Individual blood
      bactericidal capacity may have a significant effect on antimicrobial outcome.

PMID- 24587366
TI  - Prospective associations between plasma saturated, monounsaturated and
      polyunsaturated fatty acids and overall and breast cancer risk - modulation by
      antioxidants: a nested case-control study.
AB  - BACKGROUND: Mechanistic data suggest that different types of fatty acids play a
      role in carcinogenesis and that antioxidants may modulate this relationship but
      epidemiologic evidence is lacking. Our aim was to investigate the association
      between plasma saturated, monounsaturated and polyunsaturated fatty acids (SFAs,
      MUFAs and PUFAs) and overall and breast cancer risk and to evaluate the potential
      modulatory effect of an antioxidant supplementation on these relationships.
      METHODS: A nested case-control study included all first incident cancer cases
      diagnosed in the SU.VI.MAX study between 1994 and 2002 (n=250 cases, one matched
      control/case). Participants to the SU.VI.MAX randomized controlled trial received
      either vitamin/mineral antioxidants or placebo during this intervention period.
      Baseline fatty acid composition of plasma total lipids was measured by gas
      chromatography. Conditional logistic regression was performed overall and
      stratified by intervention group. RESULTS: Dihomo-gamma-linolenic acid
      (Ptrend=0.002), the dihomo-gamma-linolenic/linoleic acids ratio (Ptrend=0.001),
      mead acid (Ptrend=0.0004), and palmitoleic acid (Ptrend=0.02) were inversely
      associated with overall cancer risk. The arachidonic/dihomo-gamma-linolenic acids
      ratio (Ptrend=0.02) and linoleic acid (Ptrend=0.02) were directly associated with
      overall cancer risk. Similar results were observed for breast cancer
      specifically. In stratified analyses, associations were only observed in the
      placebo group. Notably, total PUFAs were directly associated with overall
      (Ptrend=0.02) and breast cancer risk in the placebo group only. CONCLUSION:
      Specific SFAs, MUFAs and PUFAs were prospectively differentially associated with
      cancer risk. In addition, this study suggests that antioxidants may modulate
      these associations by counteracting the potential effects of these fatty acids on
      carcinogenesis.

PMID- 24587367
TI  - Early-life exposure to bisphenol a induces liver injury in rats involvement of
      mitochondria-mediated apoptosis.
AB  - Exposure to bisphenol A (BPA), a monomer widely used to manufacture polycarbonate
      plastics, has been reported to be associated with abnormalities of liver function
      and hepatic damage. However, the molecular mechanism under the pathogenesis of
      hepatic injury is unclear. In this study, the effect of perinatal exposure to BPA
      at the reference dose of 50 ug/kg/day on the apoptotic index in the liver of rat
      offspring was investigated. Increased levels of ALT and enhanced cell apoptosis
      were observed in the liver of rat offspring at 15 and 21 weeks, and significantly
      increased activity of caspase-3 and caspase-9 and elevated levels of cytochrome c
      were also confirmed. In addition, significant change in the expression levels of
      Bcl-2 and Bax were found in BPA-treated offspring at 21 weeks. For in vitro
      experiments, liver mitochondria were isolated from neonatal rats and were treated
      with BPA. BPA treatment led to a significant increase in mitochondrial
      permeability transition. Moreover, the supernatant from BPA-treated mitochondria
      significantly increased apoptotic changes in nuclei isolated from liver tissue.
      In conclusion, the study demonstrates that BPA induces mitochondria-mediated
      apoptosis in hepatic cells, which may contribute to long-term hepatotoxicity
      induced by early-life exposure to BPA. 

PMID- 24587368
TI  - Hemokinin-1(4-11)-induced analgesia selectively up-regulates delta-opioid
      receptor expression in mice.
AB  - Our previous studies have shown that an active fragment of human tachykinins (hHK
      1(4-11)) produced an opioid-independent analgesia after intracerebroventricular
      (i.c.v.) injection in mice, which has been markedly enhanced by a delta OR
      antagonist, naltrindole hydrochloride (NTI). In this study, we have further
      characterized the in vivo analgesia after i.c.v. injection of hHK-1(4-11) in
      mouse model. Our qRT-PCR results showed that the mRNA levels of several ligands
      and receptors (e.g. PPT-A, PPT-C, KOR, PDYN and PENK) have not changed
      significantly. Furthermore, neither transcription nor expression of NK1 receptor,
      MOR and POMC have changed noticeably. In contrast, both mRNA and protein levels
      of DOR have been up-regulated significantly, indicating that the enhanced
      expression of delta opioid receptor negatively modulates the analgesia induced by
      i.c.v. injection of hHK-1(4-11). Additionally, the combinatorial data from our
      previous and present experiments strongly suggest that the discriminable
      distribution sites in the central nervous system between hHK-1(4-11) and r/mHK-1
      may be attributed to their discriminable analgesic effects. Altogether, our
      findings will not only contribute to the understanding of the complicated
      mechanisms regarding the nociceptive modulation of hemokinin-1 as well as its
      active fragments at supraspinal level, but may also lead to novel pharmacological
      interventions. 

PMID- 24587369
TI  - Ciprofloxacin enhances stress erythropoiesis in spleen and increases survival
      after whole-body irradiation combined with skin-wound trauma.
AB  - Severe hematopoietic loss is one of the major therapeutic targets after radiation
      combined injury (CI), a kind of injury resulting from radiation exposure combined
      with other traumas. In this study, we tested the use of ciprofloxacin (CIP) as a
      treatment, because of recently reported immunomodulatory effects against CI that
      may improve hematopoiesis. The CIP regimen was a daily, oral dose for 3 weeks,
      with the first dose 2 h after CI. CIP treatment improved 30-day survival in mice
      at 80% compared to 35% for untreated controls. Study of early changes in
      hematological parameters identified CI-induced progressive anemia by 10 days that
      CIP significantly ameliorated. CI induced erythropoietin (EPO) mRNA in kidney and
      protein in kidney and serum; CIP stimulated EPO mRNA expression. In spleens of CI
      mice, CIP induced bone morphogenetic protein 4 (BMP4) in macrophages with EPO
      receptors. Splenocytes from CIP-treated CI mice formed CD71+ colony-forming unit
      erythroid significantly better than those from controls. Thus, CIP-mediated BMP4
      dependent stress erythropoiesis may play a role in improving survival after CI.

PMID- 24587370
TI  - tauFCS: multi-method global analysis enhances resolution and sensitivity in
      fluorescence fluctuation measurements.
AB  - Fluorescence fluctuation methods have become invaluable research tools for
      characterizing the molecular-level physical and chemical properties of complex
      systems, such as molecular concentrations, dynamics, and the stoichiometry of
      molecular interactions. However, information recovery via curve fitting analysis
      of fluctuation data is complicated by limited resolution and challenges
      associated with identifying accurate fit models. We introduce a new approach to
      fluorescence fluctuation spectroscopy that couples multi-modal fluorescence
      measurements with multi-modal global curve fitting analysis. This approach yields
      dramatically enhanced resolution and fitting model discrimination capabilities in
      fluctuation measurements. The resolution enhancement allows the concentration of
      a secondary species to be accurately measured even when it constitutes only a few
      percent of the molecules within a sample mixture, an important new capability
      that will allow accurate measurements of molecular concentrations and interaction
      stoichiometry of minor sample species that can be functionally important but
      difficult to measure experimentally. We demonstrate this capability using tauFCS,
      a new fluctuation method which uses simultaneous global analysis of fluorescence
      correlation spectroscopy and fluorescence lifetime data, and show that tauFCS can
      accurately recover the concentrations, diffusion coefficients, lifetimes, and
      molecular brightness values for a two component mixture over a wide range of
      relative concentrations. 

PMID- 24587372
TI  - Accounting for subgroup structure in line-transect abundance estimates of false
      killer whales (Pseudorca crassidens) in Hawaiian waters.
AB  - For biological populations that form aggregations (or clusters) of individuals,
      cluster size is an important parameter in line-transect abundance estimation and
      should be accurately measured. Cluster size in cetaceans has traditionally been
      represented as the total number of individuals in a group, but group size may be
      underestimated if group members are spatially diffuse. Groups of false killer
      whales (Pseudorca crassidens) can comprise numerous subgroups that are dispersed
      over tens of kilometers, leading to a spatial mismatch between a detected group
      and the theoretical framework of line-transect analysis. Three stocks of false
      killer whales are found within the U.S. Exclusive Economic Zone of the Hawaiian
      Islands (Hawaiian EEZ): an insular main Hawaiian Islands stock, a pelagic stock,
      and a Northwestern Hawaiian Islands (NWHI) stock. A ship-based line-transect
      survey of the Hawaiian EEZ was conducted in the summer and fall of 2010,
      resulting in six systematic-effort visual sightings of pelagic (n = 5) and NWHI
      (n = 1) false killer whale groups. The maximum number and spatial extent of
      subgroups per sighting was 18 subgroups and 35 km, respectively. These sightings
      were combined with data from similar previous surveys and analyzed within the
      conventional line-transect estimation framework. The detection function, mean
      cluster size, and encounter rate were estimated separately to appropriately
      incorporate data collected using different methods. Unlike previous line-transect
      analyses of cetaceans, subgroups were treated as the analytical cluster instead
      of groups because subgroups better conform to the specifications of line-transect
      theory. Bootstrap values (n = 5,000) of the line-transect parameters were
      randomly combined to estimate the variance of stock-specific abundance estimates.
      Hawai'i pelagic and NWHI false killer whales were estimated to number 1,552 (CV =
      0.66; 95% CI = 479-5,030) and 552 (CV = 1.09; 95% CI = 97-3,123) individuals,
      respectively. Subgroup structure is an important factor to consider in line
      transect analyses of false killer whales and other species with complex grouping
      patterns. 

PMID- 24587371
TI  - Complexity of central processing in simple and choice multilimb reaction-time
      tasks.
AB  - The default mode of the motor system is a coupling between limbs. However, in
      some movements, a decoupling is required and thus calls for selection and
      facilitation/inhibition processes. Here, we investigate the relative contribution
      of recruitment versus selection processes to the overall processing complexity.
      To this aim we proposed a new multilimb reaction-time task (MUL-RT). Simple,
      choice and normalized (choice minus simple) RT were analysed together with error
      rates in thirty-six young adults for 15 coordination modes including all possible
      configuration of limb recruitment. Simple and normalized RTs were respectively
      assumed to be indicative of the recruitment and selection processes. Results
      supported a model of coupling/decoupling interactions respectively reporting
      weak, intermediate and strong interaction for selecting diagonal, ipsilateral and
      homologous limbs. Movement laterality (left vs. right) had no effect on selection
      complexity, whereas selecting upper limbs was less challenging than selecting
      lower limbs. Results in the different coordination modes suggested that
      recruitment complexity decreased as follows: 3 limbs = 4 limbs>2 limbs
      (homologous, ipsilateral and diagonal)>1 limb, and selection complexity as
      follows: 2 diagonal limbs>3 limbs>2 ipsilateral limbs>1 limb = 2 homologous
      limbs>4 limbs. Based on these ordinal scales of recruitment and selection
      complexity, we extrapolated the overall processing complexity of the simple and
      choice MUL-RT. This method was efficient in reproducing the absolute results we
      obtained on a ratio scale (ms) and demonstrated that processing complexity in
      simple RT was mainly governed by the 'recruitment principle' (the more limbs
      recruited the lower the performance), whereas contributions of recruitment and
      'selection principle' (nature of the coordination determines performance) to
      overall processing complexity were similar in choice RT. 

PMID- 24587373
TI  - Higher levels of multiple paternities increase seedling survival in the long
      lived tree Eucalyptus gracilis.
AB  - Studying associations between mating system parameters and fitness in natural
      populations of trees advances our understanding of how local environments affect
      seed quality, and thereby helps to predict when inbreeding or multiple
      paternities should impact on fitness. Indeed, for species that demonstrate
      inbreeding avoidance, multiple paternities (i.e. the number of male parents per
      half-sib family) should still vary and regulate fitness more than inbreeding-
      named here as the 'constrained inbreeding hypothesis'. We test this hypothesis in
      Eucalyptus gracilis, a predominantly insect-pollinated tree. Fifty-eight open
      pollinated progeny arrays were collected from trees in three populations. Progeny
      were planted in a reciprocal transplant trial. Fitness was measured by family
      establishment rates. We genotyped all trees and their progeny at eight
      microsatellite loci. Planting site had a strong effect on fitness, but seed
      provenance and seed provenance * planting site did not. Populations had
      comparable mating system parameters and were generally outcrossed, experienced
      low biparental inbreeding and high levels of multiple paternity. As predicted,
      seed families that had more multiple paternities also had higher fitness, and no
      fitness-inbreeding correlations were detected. Demonstrating that fitness was
      most affected by multiple paternities rather than inbreeding, we provide evidence
      supporting the constrained inbreeding hypothesis; i.e. that multiple paternity
      may impact on fitness over and above that of inbreeding, particularly for
      preferentially outcrossing trees at life stages beyond seed development.

PMID- 24587374
TI  - Transcriptomic profile reveals gender-specific molecular mechanisms driving
      multiple sclerosis progression.
AB  - BACKGROUND: Although the most common clinical presentation of multiple sclerosis
      (MS) is the so called Relapsing-Remitting MS (RRMS), the molecular mechanisms
      responsible for its progression are currently unknown. To tackle this problem, a
      whole-genome gene expression analysis has been performed on RRMS patients.
      RESULTS: The comparative analysis of the Affymetrix Human Gene 1.0 ST microarray
      data from peripheral blood leucocytes obtained from 25 patients in remission and
      relapse and 25 healthy subjects has revealed 174 genes altered in both remission
      and relapse, a high proportion of them showing what we have called "mirror
      pattern": they are upregulated in remission and downregulated in relapse or vice
      versa. The coexpression analysis of these genes has shown that they are organized
      in three female-specific and one male-specific modules. CONCLUSIONS: The
      interpretation of the modules of the coexpression network suggests that Epstein
      Barr virus (EBV) reactivation of B cells happens in MS relapses; however, qPCR
      expression data of the viral genes supports that hypothesis only in female
      patients, reinforcing the notion that different molecular processes drive disease
      progression in females and males. Besides, we propose that the "primed" state
      showed by neutrophils in women is an endogenous control mechanism triggered to
      keep EBV reactivation under control through vitamin B12 physiology. Finally, our
      results also point towards an important sex-specific role of non-coding RNA in
      MS.

PMID- 24587375
TI  - Clinical, functional and health-related quality of life correlates of clinically
      significant symptoms of anxiety and depression in patients with systemic
      sclerosis: a cross-sectional survey.
AB  - OBJECTIVES: To identify clinical, functional and health-related quality of life
      (HRQoL) correlates of clinically significant symptoms of anxiety and depression
      in patients with systemic sclerosis (SSc). METHODS: Three-hundred-and-eighty-one
      patients fulfilling the American College of Rheumatology and/or the Leroy and
      Medsger criteria for SSc were assessed for visceral involvement, disability and
      HRQoL (assessed by SF-36). Clinically significant symptoms of anxiety and
      depression were evaluated with the Hospital Anxiety Depression Scale (HAD)
      (defined cut-off>=8). RESULTS: 9.2% the patients had limited SSc, 50.5% limited
      cutaneous SSc (lcSSc), and 40.3% diffuse cutaneous SSc (dcSSc). Overall, 40.4%
      and 58.8% of the patients had clinically significant symptoms of depression and
      anxiety, respectively. Compared to patients without clinically significant
      symptoms of depression, patients with clinically significant symptoms of
      depression had poorer health status, HRQoL mental and physical component, and
      greater global disability, hand disability and aesthetic impairment. Compared to
      patients without clinically significant symptoms of anxiety, patients with
      clinically significant symptoms of anxiety had poorer SF-36 mental and physical
      component scores. On multivariable analysis, excluding mental component score of
      SF-36, variables independently associated with clinically significant symptoms of
      depression and anxiety were global disability and physical component of SF-36,
      plus female gender for clinically significant symptoms of anxiety only.
      Remarkably, patients with and without clinically significant psychiatric symptoms
      were comparable for all disease-related clinical features assessed. CONCLUSION:
      High levels of clinically significant symptoms of anxiety and depression are
      observed among SSc patients. Clinically significant psychiatric symptoms are
      rather associated with increased disability and altered HRQoL, than with disease
      specific organ manifestations.

PMID- 24587377
TI  - SNP-associations and phenotype predictions from hundreds of microbial genomes
      without genome alignments.
AB  - SNP-association studies are a starting point for identifying genes that may be
      responsible for specific phenotypes, such as disease traits. The vast bulk of
      tools for SNP-association studies are directed toward SNPs in the human genome,
      and I am unaware of any tools designed specifically for such studies in bacterial
      or viral genomes. The PPFS (Predict Phenotypes From SNPs) package described here
      is an add-on to kSNP , a program that can identify SNPs in a data set of hundreds
      of microbial genomes. PPFS identifies those SNPs that are non-randomly associated
      with a phenotype based on the chi2 probability, then uses those diagnostic SNPs
      for two distinct, but related, purposes: (1) to predict the phenotypes of strains
      whose phenotypes are unknown, and (2) to identify those diagnostic SNPs that are
      most likely to be causally related to the phenotype. In the example illustrated
      here, from a set of 68 E. coli genomes, for 67 of which the pathogenicity
      phenotype was known, there were 418,500 SNPs. Using the phenotypes of 36 of those
      strains, PPFS identified 207 diagnostic SNPs. The diagnostic SNPs predicted the
      phenotypes of all of the genomes with 97% accuracy. It then identified 97 SNPs
      whose probability of being causally related to the pathogenic phenotype was
      >0.999. In a second example, from a set of 116 E. coli genome sequences, using
      the phenotypes of 65 strains PPFS identified 101 SNPs that predicted the source
      host (human or non-human) with 90% accuracy.

PMID- 24587376
TI  - Reducing ppGpp level rescues an extreme growth defect caused by mutant EF-Tu.
AB  - Transcription and translation of mRNA's are coordinated processes in bacteria. We
      have previously shown that a mutant form of EF-Tu (Gln125Arg) in Salmonella
      Typhimurium with a reduced affinity for aa-tRNA, causes ribosome pausing,
      resulting in an increased rate of RNase E-mediated mRNA cleavage, causing
      extremely slow growth, even on rich medium. The slow growth phenotype is reversed
      by mutations that reduce RNase E activity. Here we asked whether the slow growth
      phenotype could be reversed by overexpression of a wild-type gene. We identified
      spoT (encoding ppGpp synthetase/hydrolase) as a gene that partially reversed the
      slow growth rate when overexpressed. We found that the slow-growing mutant had an
      abnormally high basal level of ppGpp that was reduced when spoT was
      overexpressed. Inactivating relA (encoding the ribosome-associated ppGpp
      synthetase) also reduced ppGpp levels and significantly increased growth rate.
      Because RelA responds specifically to deacylated tRNA in the ribosomal A-site
      this suggested that the tuf mutant had an increased level of deacylated tRNA
      relative to the wild-type. To test this hypothesis we measured the relative
      acylation levels of 4 families of tRNAs and found that proline isoacceptors were
      acylated at a lower level in the mutant strain relative to the wild-type. In
      addition, the level of the proS tRNA synthetase mRNA was significantly lower in
      the mutant strain. We suggest that an increased level of deacylated tRNA in the
      mutant strain stimulates RelA-mediated ppGpp production, causing changes in
      transcription pattern that are inappropriate for rich media conditions, and
      contributing to slow growth rate. Reducing ppGpp levels, by altering the activity
      of either SpoT or RelA, removes one cause of the slow growth and reveals the
      interconnectedness of intracellular regulatory mechanisms. 

PMID- 24587378
TI  - Integrated data management for clinical studies: automatic transformation of data
      models with semantic annotations for principal investigators, data managers and
      statisticians.
AB  - Design, execution and analysis of clinical studies involves several stakeholders
      with different professional backgrounds. Typically, principle investigators are
      familiar with standard office tools, data managers apply electronic data capture
      (EDC) systems and statisticians work with statistics software. Case report forms
      (CRFs) specify the data model of study subjects, evolve over time and consist of
      hundreds to thousands of data items per study. To avoid erroneous manual
      transformation work, a converting tool for different representations of study
      data models was designed. It can convert between office format, EDC and
      statistics format. In addition, it supports semantic annotations, which enable
      precise definitions for data items. A reference implementation is available as
      open source package ODMconverter at http://cran.r-project.org. 

PMID- 24587379
TI  - Negative pressure wound therapy decreases mortality in a murine model of burn
      wound sepsis involving Pseudomonas aeruginosa infection.
AB  - BACKGROUND: The colonization of burn wounds by Pseudomonas aeruginosa can lead to
      septic shock, organ injuries, and high mortality rates. We hypothesized that
      negative pressure wound therapy (NPWT) would decrease invasion and proliferation
      of P. aeruginosa within the burn wound and reduce mortality. METHODS: Thermal
      injuries were induced in anesthetized mice, and P. aeruginosa was applied to the
      wound surface for 24 h. After removing the burn eschar and debridement, the
      animals were subjected to either NPWT or wet-to-dry (WTD) treatment protocols.
      The bacterial loads on the wound surface were assessed during 7 d of treatment,
      as were the concentrations of inflammatory cytokines in the peripheral blood
      samples. Survival was monitored daily for 14 d after burn induction. Finally,
      samples of wounded skin, lung, liver, and kidney were collected and subjected to
      histopathological examination. RESULTS: Applying P. aeruginosa to the burn wound
      surface led to sepsis. During early stages of treatment, NPWT reduced the
      mortality of the septic animals and levels of P. aeruginosa within the burn wound
      compared with WTD-treated animals. Circulating levels of cytokines and
      cytoarchitectural abnormalities were also significantly reduced via NPWT.
      CONCLUSIONS: Our data indicate that NPWT inhibits the invasion and proliferation
      of P. aeruginosa in burn-wounded tissue and decreases early mortality in a murine
      model of burn-wound sepsis. These therapeutic benefits likely result from the
      ability of NPWT to decrease bacterial proliferation on the wound surface, reduce
      cytokine serum concentrations, and prevent damage to internal organs.

PMID- 24587380
TI  - PRB1 is required for clipping of the histone H3 N terminal tail in Saccharomyces
      cerevisiae.
AB  - Cathepsin L, a lysosomal protein in mouse embryonic stem cells has been shown to
      clip the histone H3 N- terminus, an activity associated with gene activity during
      mouse cell development. Glutamate dehydrogenase (GDH) was also identified as
      histone H3 specific protease in chicken liver, which has been connected to gene
      expression during aging. In baker's yeast, Saccharomyces cerevisiae, clipping the
      histone H3 N-terminus has been associated with gene activation in stationary
      phase but the protease responsible for the yeast histone H3 endopeptidase
      activity had not been identified. In searching for a yeast histone H3
      endopeptidase, we found that yeast vacuolar protein Prb1 is present in the
      cellular fraction enriched for the H3 N-terminus endopeptidase activity and this
      endopeptidase activity is lost in the PRB1 deletion mutant (prb1Delta). In
      addition, like Cathepsin L and GDH, purified Prb1 from yeast cleaves H3 between
      Lys23 and Ala24 in the N-terminus in vitro as shown by Edman degradation. In
      conclusion, our data argue that PRB1 is required for clipping of the histone H3 N
      terminal tail in Saccharomyces cerevisiae. 

PMID- 24587381
TI  - Enhancement of visual motion detection thresholds in early deaf people.
AB  - In deaf people, the auditory cortex can reorganize to support visual motion
      processing. Although this cross-modal reorganization has long been thought to
      subserve enhanced visual abilities, previous research has been unsuccessful at
      identifying behavioural enhancements specific to motion processing. Recently,
      research with congenitally deaf cats has uncovered an enhancement for visual
      motion detection. Our goal was to test for a similar difference between deaf and
      hearing people. We tested 16 early and profoundly deaf participants and 20
      hearing controls. Participants completed a visual motion detection task, in which
      they were asked to determine which of two sinusoidal gratings was moving. The
      speed of the moving grating varied according to an adaptive staircase procedure,
      allowing us to determine the lowest speed necessary for participants to detect
      motion. Consistent with previous research in deaf cats, the deaf group had lower
      motion detection thresholds than the hearing. This finding supports the proposal
      that cross-modal reorganization after sensory deprivation will occur for
      supramodal sensory features and preserve the output functions. 

PMID- 24587382
TI  - A model of proteostatic energy cost and its use in analysis of proteome trends
      and sequence evolution.
AB  - A model of proteome-associated chemical energetic costs of cells is derived from
      protein-turnover kinetics and protein folding. Minimization of the proteostatic
      maintenance cost can explain a range of trends of proteomes and combines both
      protein function, stability, size, proteostatic cost, temperature, resource
      availability, and turnover rates in one simple framework. We then explore the
      ansatz that the chemical energy remaining after proteostatic maintenance is
      available for reproduction (or cell division) and thus, proportional to organism
      fitness. Selection for lower proteostatic costs is then shown to be significant
      vs. typical effective population sizes of yeast. The model explains and
      quantifies evolutionary conservation of highly abundant proteins as arising both
      from functional mutations and from changes in other properties such as stability,
      cost, or turnover rates. We show that typical hypomorphic mutations can be
      selected against due to increased cost of compensatory protein expression (both
      in the mutated gene and in related genes, i.e. epistasis) rather than compromised
      function itself, although this compensation depends on the protein's importance.
      Such mutations exhibit larger selective disadvantage in abundant, large,
      synthetically costly, and/or short-lived proteins. Selection against increased
      turnover costs of less stable proteins rather than misfolding toxicity per se can
      explain equilibrium protein stability distributions, in agreement with recent
      findings in E. coli. The proteostatic selection pressure is stronger at low
      metabolic rates (i.e. scarce environments) and in hot habitats, explaining
      proteome adaptations towards rough environments as a question of energy. The
      model may also explain several trade-offs observed in protein evolution and
      suggests how protein properties can coevolve to maintain low proteostatic cost. 

PMID- 24587383
TI  - Selection for phase variation of LOS biosynthetic genes frequently occurs in
      progression of non-typeable Haemophilus influenzae infection from the nasopharynx
      to the middle ear of human patients.
AB  - Surface structures in Haemophilus influenzae are subject to rapid ON/OFF
      switching of expression, a process termed phase variation. We analyse
      tetranucleotide repeats controlling phase variation in lipo-oligosaccharide (LOS)
      genes of H. influenzae in paired isolates from both the nasopharynx and middle
      ears of paediatric patients with chronic or recurrent otitis media. A change in
      expression of at least one of the seven phase variable LOS biosynthesis genes was
      seen in 12 of the 21 strain pairs. Several strains showed switching of expression
      in multiple LOS genes, consistent with a key role for phase variable LOS
      biosynthetic genes in human infection. 

PMID- 24587384
TI  - Biophysical interactions control the size and abundance of large phytoplankton
      chains at the Ushant tidal front.
AB  - Phytoplankton blooms are usually dominated by chain-forming diatom species that
      can alter food pathways from primary producers to predators by reducing the
      interactions between intermediate trophic levels. The food-web modifications are
      determined by the length of the chains; however, the estimation is biased because
      traditional sampling strategies damage the chains and, therefore, change the
      phytoplankton size structure. Sedimentological studies around oceanic fronts have
      shown high concentrations of giant diatom mats (>1 cm in length), suggesting that
      the size of diatom chains is underestimated in the pelagic realm. Here, we
      investigate the variability in size and abundance of phytoplankton chains at the
      Ushant tidal front (NW France) using the Video Fluorescence Analyzer (VFA), a
      novel and non-invasive system. CTD and Scanfish profiling characterized a strong
      temperature and chlorophyll front, separating mixed coastal waters from the
      oceanic-stratified domain. In order to elucidate spring-neap variations in the
      front, vertical microstructure profiler was used to estimate the turbulence and
      vertical nitrate flux. Key findings were: (1) the VFA system recorded large
      diatom chains up to 10.7 mm in length; (2) chains were mainly distributed in the
      frontal region, with maximum values above the pycnocline in coincidence with the
      maximum chlorophyll; (3) the diapycnal fluxes of nitrate enabled the maintenance
      of the bloom in the frontal area throughout the spring-neap tidal cycle; (4) from
      spring to neap tide the chains length was significantly reduced; (5) during neap
      tide, the less intense vertical diffusion of nutrients, as well as the lower
      turbulence around the chains, intensified nutrient-depleted conditions and, thus,
      very large chains became disadvantageous. To explain this pattern, we suggest
      that size plasticity is an important ecological trait driving phytoplankton
      species competition. Although this plasticity behavior is well known from
      experiments in the laboratory, it has never been reported from observations in
      the field. 

PMID- 24587386
TI  - Association of meteorological factors with pediatric intussusception in
      subtropical china: a 5-year analysis.
AB  - PURPOSE: The aim of this study was to determine whether climate factors correlate
      with variations in the rate of pediatric intussusception cases presenting to the
      Children's Hospital in Suzhou, China. MATERIAL AND METHODS: The hospital records
      of 5,994 pediatric cases of intussusception who had presented between Aug 2006
      and Dec 2011 were retrospectively analyzed. Demographic data and air enema
      reduction data were collected for each case. RESULTS: The monthly rate of new
      intussusception cases fluctuated throughout the year generally rising from April
      to September with a peak from May to July. This annual cycling of intussusception
      incidence was highly significant over the 5 year observation period. Poisson
      regression analysis showed that the monthly number of intussusception cases was
      associated with an increase in mean temperature per month (P = 0.0001), sum of
      sunshine per month (P<0.0001), precipitation per month (P<0.0001), and was
      marginally associated with increased mean wind speed per month (P = 0.0709).
      CONCLUSION: The incidence of intussusception in Suzhou was seasonally variable
      with a peak in cases presenting during hotter, sunnier, and wetter months
      demonstrating a positive association with certain climatic factors.

PMID- 24587385
TI  - Sulforaphane inhibits invasion via activating ERK1/2 signaling in human
      glioblastoma U87MG and U373MG cells.
AB  - BACKGROUND: Glioblastoma has highly invasive potential, which might result in
      poor prognosis and therapeutic failure. Hence, the key we study is to find
      effective therapies to repress migration and invasion. Sulforaphane (SFN) was
      demonstrated to inhibit cell growth in a variety of tumors. Here, we will further
      investigate whether SFN inhibits migration and invasion and find the possible
      mechanisms in human glioblastoma U87MG and U373MG cells. METHODS: First, the
      optimal time and dose of SFN for migration and invasion study were determined via
      cell viability and cell morphological assay. Further, scratch assay and transwell
      invasion assay were employed to investigate the effect of SFN on migration and
      invasion. Meanwhile, Western blots were used to detect the molecular linkage
      among invasion related proteins phosphorylated ERK1/2, matrix metalloproteinase-2
      (MMP-2) and CD44v6. Furthermore, Gelatin zymography was performed to detect the
      inhibition of MMP-2 activation. In addition, ERK1/2 blocker PD98059 (25 uM) was
      integrated to find the link between activated ERK1/2 and invasion, MMP-2 and
      CD44v6. RESULTS: The results showed that SFN (20 uM) remarkably reduced the
      formation of cell pseudopodia, indicating that SFN might inhibit cell motility.
      As expected, scratch assay and transwell invasion assay showed that SFN inhibited
      glioblastoma cell migration and invasion. Western blot and Gelatin zymography
      showed that SFN phosphorylated ERK1/2 in a sustained way, which contributed to
      the downregulated MMP-2 expression and activity, and the upregulated CD44v6
      expression. These molecular interactions resulted in the inhibition of cell
      invasion. CONCLUSIONS: SFN inhibited migration and invasion processes.
      Furthermore, SFN inhibited invasion via activating ERK1/2 in a sustained way. The
      accumulated ERK1/2 activation downregulated MMP-2 expression and decreased its
      activity and upregulated CD44v6. SFN might be a potential therapeutic agent by
      activating ERK1/2 signaling against human glioblastoma.

PMID- 24587387
TI  - Diversifying selection on the thrombospondin-related adhesive protein (TRAP) gene
      of Plasmodium falciparum in Thailand.
AB  - Sporozoites of Plasmodium falciparum are transmitted to human hosts by Anopheles
      mosquitoes. Thrombospondin-related adhesive protein (TRAP) is expressed in
      sporozoites and plays a crucial role in sporozoite gliding and invasion of human
      hepatocytes. A previous study showed that the TRAP gene has been subjected to
      balancing selection in the Gambian P. falciparum population. To further study the
      molecular evolution of the TRAP gene in Plasmodium falciparum, we investigated
      TRAP polymorphisms in P. falciparum isolates from Suan Phueng District in
      Ratchaburi Province, Thailand. The analysis of the entire TRAP coding sequences
      in 32 isolates identified a total of 39 single nucleotide polymorphisms (SNPs),
      which comprised 37 nonsynonymous and two synonymous SNPs. McDonald-Kreitman test
      showed that the ratio of the number of nonsynonymous to synonymous polymorphic
      sites within P. falciparum was significantly higher than that of the number of
      nonsynonymous to synonymous fixed sites between P. falciparum and P. reichenowi.
      Furthermore, the rate of nonsynonymous substitution was significantly higher than
      that of synonymous substitution within Thai P. falciparum. These results indicate
      that the TRAP gene has been subject to diversifying selection in the Thai P.
      falciparum population as well as the Gambian P. falciparum population. Comparison
      of our P. falciparum isolates with those from another region of Thailand (Tak
      province, Thailand) revealed that TRAP was highly differentiated between
      geographically close regions. This rapid diversification seems to reflect strong
      recent positive selection on TRAP. Our results suggest that the TRAP molecule is
      a major target of the human immune response to pre-erythrocytic stages of P.
      falciparum. 

PMID- 24587390
TI  - From trap to nursery. Mitigating the impact of an artisanal fishery on cuttlefish
      offspring.
AB  - BACKGROUND: Overexploitation and the impact of several types of human activities
      have caused declines of marine resources. The direct and active involvement of
      fishermen in the management of marine resources is effective not only for
      resource conservation, but also for changing fishermen's attitudes. In this
      study, we proposed and tested the efficacy and suitability of a measure for
      mitigating the impact of a trap fishery on cuttlefish eggs in the North Adriatic
      Sea. This measure directly involves fishermen in promoting the conservation of
      the early, and more vulnerable, stages of the cuttlefish life cycle.
      METHODOLOGY/PRINCIPAL FINDINGS: Through surveys on fishing boats and interviews
      with fishermen, we found that traps placed in coastal areas during the cuttlefish
      breeding season have a high impact on cuttlefish eggs, with over 3 million eggs
      likely being destroyed by 3750 traps of 15 fishermen in less than 3 miles of
      coast. The use of removable ropes attached inside traps as an additional
      substrate for egg deposition allowed the recovery of 23.7% of the eggs deposited
      on the traps on average, without affecting the catch rate of adults. Experiments
      examining hatching success in the field highlighted the need for a careful choice
      of hatching sites to maximise the efficacy of the mitigation measure.
      CONCLUSIONS/SIGNIFICANCE: The proposed mitigation measure reduced the impact of
      fishing on cuttlefish eggs, with no significant effect on the commercial catch.
      Fishermen showed a positive attitude towards the application of this measure,
      which is inexpensive and easy to employ. The direct involvement of fishermen in
      the management of this resource and the maintenance of traditional fishing
      methods are a novel aspect of the proposed measure and represent the basis for
      its success.

PMID- 24587388
TI  - Blood platelets in the progression of Alzheimer's disease.
AB  - Alzheimer's disease (AD) is characterized by neurotoxic amyloid-beta plaque
      formation in brain parenchyma and cerebral blood vessels known as cerebral
      amyloid angiopathy (CAA). Besides CAA, AD is strongly related to vascular
      diseases such as stroke and atherosclerosis. Cerebrovascular dysfunction occurs
      in AD patients leading to alterations in blood flow that might play an important
      role in AD pathology with neuronal loss and memory deficits. Platelets are the
      major players in hemostasis and thrombosis, but are also involved in
      neuroinflammatory diseases like AD. For many years, platelets were accepted as
      peripheral model to study the pathophysiology of AD because platelets display the
      enzymatic activities to generate amyloid-beta (Abeta) peptides. In addition,
      platelets are considered to be a biomarker for early diagnosis of AD. Effects of
      Abeta peptides on platelets and the impact of platelets in the progression of AD
      remained, however, ill-defined. The present study explored the cellular
      mechanisms triggered by Abeta in platelets. Treatment of platelets with Abeta led
      to platelet activation and enhanced generation of reactive oxygen species (ROS)
      and membrane scrambling, suggesting enhanced platelet apoptosis. More important,
      platelets modulate soluble Abeta into fibrillar structures that were absorbed by
      apoptotic but not vital platelets. This together with enhanced platelet adhesion
      under flow ex vivo and in vivo and platelet accumulation at amyloid deposits of
      cerebral vessels of AD transgenic mice suggested that platelets are major
      contributors of CAA inducing platelet thrombus formation at vascular amyloid
      plaques leading to vessel occlusion critical for cerebrovascular events like
      stroke. 

PMID- 24587389
TI  - Platelet-rich plasma (PRP) for acute muscle injury: a systematic review.
AB  - INTRODUCTION: Acute muscle injury is one of the commonest injuries that often
      result in loss of training and competition time. The best management for muscle
      injury has not been identified. Sports medicine practitioners used several
      approaches in attempt to accelerate time to recovery from muscle injury. More
      recently growing interest focussed on autologous blood product injection.
      METHODS: A literature search was conducted systematically using OvidMEDLINE,
      PubMed, EMBASE, SPORTDiscus and CINAHL databases to retrieve articles published
      until December 2012. Controlled trials and controlled laboratory studies
      comparing different strategies to promote early recovery of muscle injury were
      included. The methodological quality of studies was assessed. RESULTS: There are
      limited studies on the effects of PRP therapy for muscle injury. Three in vivo
      laboratory studies and one pilot human study were reviewed. The laboratory
      studies reported histological evidence on significant acceleration of muscle
      healing in animals treated with autologous conditioned serum (ACS), platelet-rich
      plasma (PRP) and platelet rich fibrin matrix (PRFM). A pilot human study found
      athletes treated with repeated ACS injection recovers significantly faster than
      retrospective controls. CONCLUSION: Several in vivo laboratory studies suggest
      beneficial effects of ACS, PRP and PRFM in accelerating muscle recovery. Evidence
      to suggest similar effects on humans is however limited, as valuable information
      from robust human controlled trials is still not available at this moment. Hence,
      more studies of satisfactory methodological quality with platelet-rich plasma
      interventions on muscle injury are justified.

PMID- 24587391
TI  - NMR characterization of the near native and unfolded states of the PTB domain of
      Dok1: alternate conformations and residual clusters.
AB  - BACKGROUND: Phosphotyrosine binding (PTB) domains are critically involved in
      cellular signaling and diseases. PTB domains are categorized into three distinct
      structural classes namely IRS-like, Shc-like and Dab-like. All PTB domains
      consist of a core pleckstrin homology (PH) domain with additional structural
      elements in Shc and Dab groups. The core PH fold of the PTB domain contains a
      seven stranded beta-sheet and a long C-terminal helix. PRINCIPAL FINDINGS: In
      this work, the PTB domain of Dok1 protein has been characterized, by use of NMR
      spectroscopy, in solutions containing sub-denaturing and denaturing
      concentrations of urea. We find that the Dok1 PTB domain displays, at sub
      denaturing concentrations of urea, alternate conformational states for residues
      located in the C-terminal helix and in the beta5 strand of the beta-sheet region.
      The beta5 strand of PTB domain has been found to be experiencing significant
      chemical shift perturbations in the presence of urea. Notably, many of these
      residues in the helix and in the beta5 strand are also involved in ligand
      binding. Structural and dynamical analyses at 7 M urea showed that the PTB domain
      is unfolded with islands of motionally restricted regions in the polypeptide
      chain. Further, the C-terminal helix appears to be persisted in the unfolded
      state of the PTB domain. By contrast, residues encompassing beta-sheets, loops,
      and the short N-terminal helix lack any preferred secondary structures. Moreover,
      these residues demonstrated an intimate contact with the denaturant.
      SIGNIFICANCE: This study implicates existence of alternate conformational states
      around the ligand binding pocket of the PTB domain either in the native or in the
      near native conditions. Further, the current study demonstrates that the C
      terminal helical region of PTB domain may be considered as a potential site for
      the initiation of folding.

PMID- 24587392
TI  - Dietary zinc is a key environmental modifier in the progression of IgA
      nephropathy.
AB  - IgA nephropathy (IgAN) shows diverse epidemiological characteristics, resulting
      from both genetic and acquired (e.g., environmental) causes. Environmental
      factors, such as diet or exposure to exogenous antigens, may prescribe the
      progression or prognosis of IgAN. It remains unclear as to how diet and infection
      influence susceptibility to IgAN. A relationship, such as Toll-like receptors
      (TLRs), especially TLR9 and TLR4, was demonstrated between IgAN and pathogen
      recognition molecules. Recently, zinc (Zn) was discovered to be involved in
      various immune-related diseases, affecting B, T, and dendritic cells (DCs). This
      study investigates the relationship between dietary Zn and IgAN development in
      IgAN-prone mice. Seven-week-old IgAN-prone mice were divided into low, normal,
      and high Zn diet groups. To assess exogenous pathogen-mediated immune responses,
      lipopolysaccharide (LPS) was nasally administered. The activity of IgAN was
      biochemically and pathologically evaluated during the disease course. We also
      examined in vitro IgA production in spleen cells or in combinations of cocultured
      B, T, and DCs under various Zn conditions with or without LPS. Dietary
      conditioning with Zn affected serum immunoglobulins and urinary albumin levels,
      and mesangial deposition of IgA and IgG. Zn deficiency is associated with IgAN
      progression through the activation of the TLR4/TIR-domain-containing adapter
      inducing interferon-beta (TRIF), but not the TLR9, in DCs. Zn supplementation
      prevented disease aggravation. Our findings indicate that immune conditioning
      with dietary Zn alters nephritogenic IgA production after mucosal infection. 

PMID- 24587393
TI  - Evaluation of hydrodynamic chromatography coupled with UV-visible, fluorescence
      and inductively coupled plasma mass spectrometry detectors for sizing and
      quantifying colloids in environmental media.
AB  - In this study, we evaluated hydrodynamic chromatography (HDC) coupled with
      inductively coupled plasma mass spectrometry (ICP-MS) for the analysis of
      nanoparticles in environmental samples. Using two commercially available columns
      (Polymer Labs-PDSA type 1 and 2), a set of well characterised calibrants and a
      new external time marking method, we showed that flow rate and eluent composition
      have few influence on the size resolution and, therefore, can be adapted to the
      sample particularity. Monitoring the agglomeration of polystyrene nanoparticles
      over time succeeded without observable disagglomeration suggesting that even weak
      agglomerates can be measured using HDC. Simultaneous determination of gold
      colloid concentration and size using ICP-MS detection was validated for elemental
      concentrations in the ppb range. HDC-ICP-MS was successfully applied to samples
      containing a high organic and ionic background. Indeed, online combination of UV
      visible, fluorescence and ICP-MS detectors allowed distinguishing between organic
      molecules and inorganic colloids during the analysis of Ag nanoparticles in
      synthetic surface waters and TiO2 and ZnO nanoparticles in commercial sunscreens.
      Taken together, our results demonstrate that HDC-ICP-MS is a flexible, sensitive
      and reliable method to measure the size and the concentration of inorganic
      colloids in complex media and suggest that there may be a promising future for
      the application of HDC in environmental science. Nonetheless the rigorous
      measurements of agglomerates and of matrices containing natural colloids still
      need to be studied in detail.

PMID- 24587394
TI  - Incidence of hepatitis C infection among prisoners by routine laboratory values
      during a 20-year period.
AB  - BACKGROUND: To estimate the incidence of Hepatitis C virus (HCV) and the
      predictive factors through repeated routine laboratory analyses. METHODS: An
      observational cohort study was carried out in Quatre Camins Prison, Barcelona.
      The study included subjects with an initial negative HCV result and routine
      laboratory analyses containing HCV serology from 1992 to 2011. The incidence of
      infection was calculated for the study population and for sub-groups by 100
      person-years of follow-up (100 py). The predictive factors were determined
      through Kaplan-Meier curves and a Cox regression. Hazard ratios (HR) and 95%
      confidence intervals (CI) were calculated. RESULTS: A total of 2,377 prisoners
      were included with a median follow-up time of 1,540.9 days per patient. Among the
      total population, 117 HCV seroconversions were detected (incidence of 1.17/100
      py). The incidence was higher between 1992 and 1995 (2.57/100 py), among cases
      with HIV co-infection (8.34/100 py) and among intravenous drug users (IDU)
      without methadone treatment (MT) during follow-up (6.66/100 py). The incidence
      rate of HCV seroconversion among cases with a history of IDU and current MT was
      1.35/100 py, which is close to that of the total study population. The following
      variables had a positive predictive value for HCV infection: IDU (p<0.001; HR =
      7,30; CI: 4.83-11.04), Spanish ethnicity (p = 0.009; HR = 2,03; CI: 1.93-3.44)
      and HIV infection (p = 0.015; HR = 1.97; CI: 1.14-3.39). CONCLUSION: The
      incidence of HCV infection among prisoners was higher during the first part of
      the study and among IDU during the entire study period. Preventative programs
      should be directed toward this sub-group of the prison population.

PMID- 24587396
TI  - Risky business: do native rodents use habitat and odor cues to manage predation
      risk in Australian deserts?
AB  - In open, arid environments with limited shelter there may be strong selection on
      small prey species to develop behaviors that facilitate predator avoidance. Here,
      we predicted that rodents should avoid predator odor and open habitats to reduce
      their probability of encounter with potential predators, and tested our
      predictions using a native Australian desert rodent, the spinifex hopping-mouse
      (Notomys alexis). We tested the foraging and movement responses of N. alexis to
      non-native predator (fox and cat) odor, in sheltered and open macro- and
      microhabitats. Rodents did not respond to predator odor, perhaps reflecting the
      inconsistent selection pressure that is imposed on prey species in the desert
      environment due to the transience of predator-presence. However, they foraged
      primarily in the open and moved preferentially across open sand. The results
      suggest that N. alexis relies on escape rather than avoidance behavior when
      managing predation risk, with its bipedal movement probably allowing it to
      exploit open environments most effectively. 

PMID- 24587395
TI  - Extra-cellular matrix proteins induce matrix metalloproteinase-1 (MMP-1) activity
      and increase airway smooth muscle contraction in asthma.
AB  - Airway remodelling describes the histopathological changes leading to fixed
      airway obstruction in patients with asthma and includes extra-cellular matrix
      (ECM) deposition. Matrix metalloproteinase-1 (MMP-1) is present in remodelled
      airways but its relationship with ECM proteins and the resulting functional
      consequences are unknown. We used airway smooth muscle cells (ASM) and bronchial
      biopsies from control donors and patients with asthma to examine the regulation
      of MMP-1 by ECM in ASM cells and the effect of MMP-1 on ASM contraction. Collagen
      I and tenascin-C induced MMP-1 protein expression, which for tenascin-C, was
      greater in asthma derived ASM cells. Tenascin-C induced MMP-1 expression was
      dependent on ERK1/2, JNK and p38 MAPK activation and attenuated by function
      blocking antibodies against the beta1 and beta3 integrin subunits. Tenascin-C and
      MMP-1 were not expressed in normal airways but co-localised in the ASM bundles
      and reticular basement membrane of patients with asthma. Further, ECM from asthma
      derived ASM cells stimulated MMP-1 expression to a greater degree than ECM from
      normal ASM. Bradykinin induced contraction of ASM cells seeded in 3D collagen
      gels was reduced by the MMP inhibitor ilomastat and by siRNA knockdown of MMP-1.
      In summary, the induction of MMP-1 in ASM cells by tenascin-C occurs in part via
      integrin mediated MAPK signalling. MMP-1 and tenascin-C are co-localised in the
      smooth muscle bundles of patients with asthma where this interaction may
      contribute to enhanced airway contraction. Our findings suggest that ECM changes
      in airway remodelling via MMP-1 could contribute to an environment promoting
      greater airway narrowing in response to broncho-constrictor stimuli and worsening
      asthma symptoms. 

PMID- 24587397
TI  - Respiratory syncytial virus infections enhance cigarette smoke induced COPD in
      mice.
AB  - Respiratory syncytial viral (RSV) infections are a frequent cause of chronic
      obstructive pulmonary disease (COPD) exacerbations, which are a major factor in
      disease progression and mortality. RSV is able to evade antiviral defenses to
      persist in the lungs of COPD patients. Though RSV infection has been identified
      in COPD, its contribution to cigarette smoke-induced airway inflammation and lung
      tissue destruction has not been established. Here we examine the long-term
      effects of cigarette smoke exposure, in combination with monthly RSV infections,
      on pulmonary inflammation, protease production and remodeling in mice. RSV
      exposures enhanced the influx of macrophages, neutrophils and lymphocytes to the
      airways of cigarette smoke exposed C57BL/6J mice. This infiltration of cells was
      most pronounced around the vasculature and bronchial airways. By itself, RSV
      caused significant airspace enlargement and fibrosis in mice and these effects
      were accentuated with concomitant smoke exposure. Combined stimulation with both
      smoke and RSV synergistically induced cytokine (IL-1alpha, IL-17, IFN-gamma, KC,
      IL-13, CXCL9, RANTES, MIF and GM-CSF) and protease (MMP-2, -8, -12, -13, -16 and
      cathepsins E, S, W and Z) expression. In addition, RSV exposure caused marked
      apoptosis within the airways of infected mice, which was augmented by cigarette
      smoke exposure. RSV and smoke exposure also reduced protein phosphatase 2A (PP2A)
      and protein tyrosine phosphates (PTP1B) expression and activity. This is
      significant as these phosphatases counter smoke-induced inflammation and protease
      expression. Together, these findings show for the first time that recurrent RSV
      infection markedly enhances inflammation, apoptosis and tissue destruction in
      smoke-exposed mice. Indeed, these results indicate that preventing RSV
      transmission and infection has the potential to significantly impact on COPD
      severity and progression. 

PMID- 24587398
TI  - Imaging neuroinflammation in vivo in a neuropathic pain rat model with near
      infrared fluorescence and 19F magnetic resonance.
AB  - Chronic neuropathic pain following surgery represents a serious worldwide health
      problem leading to life-long treatment and the possibility of significant
      disability. In this study, neuropathic pain was modeled using the chronic
      constriction injury (CCI). The CCI rats exhibit mechanical hypersensitivity
      (typical neuropathic pain symptom) to mechanical stimulation of the affected paw
      11 days post surgery, at a time when sham surgery animals do not exhibit
      hypersensitivity. Following a similar time course, TRPV1 gene expression appears
      to rise with the hypersensitivity to mechanical stimulation. Recent studies have
      shown that immune cells play a role in the development of neuropathic pain. To
      further explore the relationship between neuropathic pain and immune cells, we
      hypothesize that the infiltration of immune cells into the affected sciatic nerve
      can be monitored in vivo by molecular imaging. To test this hypothesis, an
      intravenous injection of a novel perfluorocarbon (PFC) nanoemulsion, which is
      phagocytosed by inflammatory cells (e.g. monocytes and macrophages), was used in
      a rat CCI model. The nanoemulsion carries two distinct imaging agents, a near
      infrared (NIR) lipophilic fluorescence reporter (DiR) and a 19F MRI (magnetic
      resonance imaging) tracer, PFC. We demonstrate that in live rats, NIR
      fluorescence is concentrated in the area of the affected sciatic nerve.
      Furthermore, the 19FF MRI signal was observed on the sciatic nerve. Histological
      examination of the CCI sciatic nerve reveals significant infiltration of CD68
      positive macrophages. These results demonstrate that the infiltration of immune
      cells into the sciatic nerve can be visualized in live animals using these
      methods.

PMID- 24587399
TI  - Plasticity in the macromolecular-scale causal networks of cell migration.
AB  - Heterogeneous and dynamic single cell migration behaviours arise from a complex
      multi-scale signalling network comprising both molecular components and
      macromolecular modules, among which cell-matrix adhesions and F-actin directly
      mediate migration. To date, the global wiring architecture characterizing this
      network remains poorly defined. It is also unclear whether such a wiring pattern
      may be stable and generalizable to different conditions, or plastic and context
      dependent. Here, synchronous imaging-based quantification of migration system
      organization, represented by 87 morphological and dynamic macromolecular module
      features, and migration system behaviour, i.e., migration speed, facilitated
      Granger causality analysis. We thereby leveraged natural cellular heterogeneity
      to begin mapping the directionally specific causal wiring between organizational
      and behavioural features of the cell migration system. This represents an
      important advance on commonly used correlative analyses that do not resolve
      causal directionality. We identified organizational features such as adhesion
      stability and adhesion F-actin content that, as anticipated, causally influenced
      cell migration speed. Strikingly, we also found that cell speed can exert causal
      influence over organizational features, including cell shape and adhesion complex
      location, thus revealing causality in directions contradictory to previous
      expectations. Importantly, by comparing unperturbed and signalling-modulated
      cells, we provide proof-of-principle that causal interaction patterns are in fact
      plastic and context dependent, rather than stable and generalizable. 

PMID- 24587400
TI  - Cross-modal re-organization in adults with early stage hearing loss.
AB  - Cortical cross-modal re-organization, or recruitment of auditory cortical areas
      for visual processing, has been well-documented in deafness. However, the degree
      of sensory deprivation necessary to induce such cortical plasticity remains
      unclear. We recorded visual evoked potentials (VEP) using high-density
      electroencephalography in nine persons with adult-onset mild-moderate hearing
      loss and eight normal hearing control subjects. Behavioral auditory performance
      was quantified using a clinical measure of speech perception-in-noise. Relative
      to normal hearing controls, adults with hearing loss showed significantly larger
      P1, N1, and P2 VEP amplitudes, decreased N1 latency, and a novel positive
      component (P2') following the P2 VEP. Current source density reconstruction of
      VEPs revealed a shift toward ventral stream processing including activation of
      auditory temporal cortex in hearing-impaired adults. The hearing loss group
      showed worse than normal speech perception performance in noise, which was
      strongly correlated with a decrease in the N1 VEP latency. Overall, our findings
      provide the first evidence that visual cross-modal re-organization not only
      begins in the early stages of hearing impairment, but may also be an important
      factor in determining behavioral outcomes for listeners with hearing loss, a
      finding which demands further investigation. 

PMID- 24587401
TI  - Validation and comparison of two methods to assess human energy expenditure
      during free-living activities.
AB  - BACKGROUND: The measurement of activity energy expenditure (AEE) via
      accelerometry is the most commonly used objective method for assessing human
      daily physical activity and has gained increasing importance in the medical,
      sports and psychological science research in recent years. OBJECTIVE: The purpose
      of this study was to determine which of the following procedures is more accurate
      to determine the energy cost during the most common everyday life activities; a
      single regression or an activity based approach. For this we used a device that
      utilizes single regression models (GT3X, ActiGraph Manufacturing Technology Inc.,
      FL., USA) and a device using activity-dependent calculation models (move II,
      movisens GmbH, Karlsruhe, Germany). MATERIAL AND METHODS: Nineteen adults (11
      male, 8 female; 30.4+/-9.0 years) wore the activity monitors attached to the
      waist and a portable indirect calorimeter (IC) as reference measure for AEE while
      performing several typical daily activities. The accuracy of the two devices for
      estimating AEE was assessed as the mean differences between their output and the
      reference and evaluated using Bland-Altman analysis. RESULTS: The GT3X
      overestimated the AEE of walking (GT3X minus reference, 1.26 kcal/min), walking
      fast (1.72 kcal/min), walking up-/downhill (1.45 kcal/min) and walking upstairs
      (1.92 kcal/min) and underestimated the AEE of jogging (-1.30 kcal/min) and
      walking upstairs (-2.46 kcal/min). The errors for move II were smaller than those
      for GT3X for all activities. The move II overestimated AEE of walking (move II
      minus reference, 0.21 kcal/min), walking up-/downhill (0.06 kcal/min) and stair
      walking (upstairs: 0.13 kcal/min; downstairs: 0.29 kcal/min) and underestimated
      AEE of walking fast (-0.11 kcal/min) and jogging (-0.93 kcal/min). CONCLUSIONS:
      Our data suggest that the activity monitor using activity-dependent calculation
      models is more appropriate for predicting AEE in daily life than the activity
      monitor using a single regression model.

PMID- 24587402
TI  - The concentration of iron in real-world geogenic PM10 is associated with
      increased inflammation and deficits in lung function in mice.
AB  - BACKGROUND: There are many communities around the world that are exposed to high
      levels of particulate matter <10 um (PM10) of geogenic (earth derived) origin.
      Mineral dusts in the occupational setting are associated with poor lung health,
      however very little is known about the impact of heterogeneous community derived
      particles. We have preliminary evidence to suggest that the concentration of iron
      (Fe) may be associated with the lung inflammatory response to geogenic PM10. We
      aimed to determine which physico-chemical characteristics of community sampled
      geogenic PM10 are associated with adverse lung responses. METHODS: We collected
      geogenic PM10 from four towns in the arid regions of Western Australia. Adult
      female BALB/c mice were exposed to 100 ug of particles and assessed for
      inflammatory and lung function responses 6 hours, 24 hours and 7 days post
      exposure. We assessed the physico-chemical characteristics of the particles and
      correlated these with lung outcomes in the mice using principal components
      analysis and multivariate linear regression. RESULTS: Geogenic particles induced
      an acute inflammatory response that peaked 6 hours post-exposure and a deficit in
      lung mechanics 7 days post-exposure. This deficit in lung mechanics was
      positively associated with the concentration of Fe and particle size variability
      and inversely associated with the concentration of Si. CONCLUSIONS: The lung
      response to geogenic PM10 is complex and highly dependent on the physico-chemical
      characteristics of the particles. In particular, the concentration of Fe in the
      particles may be a key indicator of the potential population health consequences
      for inhaling geogenic PM10.

PMID- 24587403
TI  - Identification of suitable reference genes for gene expression normalization in
      qRT-PCR analysis in watermelon.
AB  - Watermelon is one of the major Cucurbitaceae crops and the recent availability of
      genome sequence greatly facilitates the fundamental researches on it.
      Quantitative real-time reverse transcriptase PCR (qRT-PCR) is the preferred
      method for gene expression analyses, and using validated reference genes for
      normalization is crucial to ensure the accuracy of this method. However, a
      systematic validation of reference genes has not been conducted on watermelon. In
      this study, transcripts of 15 candidate reference genes were quantified in
      watermelon using qRT-PCR, and the stability of these genes was compared using
      geNorm and NormFinder. geNorm identified ClTUA and ClACT, ClEF1alpha and ClACT,
      and ClCAC and ClTUA as the best pairs of reference genes in watermelon organs and
      tissues under normal growth conditions, abiotic stress, and biotic stress,
      respectively. NormFinder identified ClYLS8, ClUBCP, and ClCAC as the best single
      reference genes under the above experimental conditions, respectively. ClYLS8 and
      ClPP2A were identified as the best reference genes across all samples. Two to
      nine reference genes were required for more reliable normalization depending on
      the experimental conditions. The widely used watermelon reference gene 18SrRNA
      was less stable than the other reference genes under the experimental conditions.
      Catalase family genes were identified in watermelon genome, and used to validate
      the reliability of the identified reference genes. ClCAT1and ClCAT2 were induced
      and upregulated in the first 24 h, whereas ClCAT3 was downregulated in the leaves
      under low temperature stress. However, the expression levels of these genes were
      significantly overestimated and misinterpreted when 18SrRNA was used as a
      reference gene. These results provide a good starting point for reference gene
      selection in qRT-PCR analyses involving watermelon. 

PMID- 24587404
TI  - HIV-1 entry and trans-infection of astrocytes involves CD81 vesicles.
AB  - Astrocytes are extensively infected with HIV-1 in vivo and play a significant
      role in the development of HIV-1-associated neurocognitive disorders. Despite
      their extensive infection, little is known about how astrocytes become infected,
      since they lack cell surface CD4 expression. In the present study, we
      investigated the fate of HIV-1 upon infection of astrocytes. Astrocytes were
      found to bind and harbor virus followed by biphasic decay, with HIV-1 detectable
      out to 72 hours. HIV-1 was observed to associate with CD81-lined vesicle
      structures. shRNA silencing of CD81 resulted in less cell-associated virus but no
      loss of co-localization between HIV-1 and CD81. Astrocytes supported trans
      infection of HIV-1 to T-cells without de novo virus production, and the virus
      containing compartment required 37 degrees C to form, and was trypsin-resistant.
      The CD81 compartment observed herein, has been shown in other cell types to be a
      relatively protective compartment. Within astrocytes, this compartment may be
      actively involved in virus entry and/or spread. The ability of astrocytes to
      transfer virus, without de novo viral synthesis suggests they are capable of
      sequestering and protecting virus and thus, they could potentially facilitate
      viral dissemination in the CNS. 

PMID- 24587405
TI  - Electrophysiological assessment of the effects of obstructive sleep apnea on
      cognition.
AB  - We used electrophysiological measures to investigate the effects of obstructive
      sleep apnea on attention, learning, and memory. Thirty subjects (OSA group, n =
      15, control group n = 15) participated in n-back tests, accompanied by P300
      recordings, to investigate working memory and attention. The mirror-drawing test
      was used to study procedural memory, and the trail-making test (TMT) was used to
      evaluate divided attention and executive function. No significant group
      difference in reaction time was found in the 0-back and 1-back tests. In the 2
      back test, reaction times of patients were longer than those of the control
      group. No P300 wave was obtained in the OSA group in any (0-, 1-, or 2-back) n
      back test. In contrast, in the control group, significant P300 waves were
      recorded except for the 2-back test. The mirror-drawing scores were unaffected by
      sleep apnea. There was no difference between groups in the TMT-A test on any of
      the trials. Although no group difference was found in the first or second trials
      of the TMT-B test, OSA patients were less successful in learning on the third
      trial. According to our study results, OSA affects attention and executive
      function adversely however, we could not detect a significant effect on working
      or procedural memory. 

PMID- 24587406
TI  - Interspecific, spatial and temporal variability of self-recruitment in
      anemonefishes.
AB  - Polymorphic microsatellite DNA parentage analysis was used to investigate the
      spatio-temporal variability of self-recruitment in populations of two
      anemonefishes: Amphiprion ocellaris and A. perideraion. Tissue samples of A.
      ocellaris (n = 364) and A. perideraion (n = 105) were collected from fringing
      reefs around two small islands (Barrang Lompo and Samalona) in Spermonde
      Archipelago, Indonesia. Specimens were genotyped based on seven microsatellite
      loci for A. ocellaris and five microsatellite loci for A. perideraion, and
      parentage assignment as well as site fidelity were calculated. Both species
      showed high levels of self-recruitment: 65.2% of juvenile A. ocellaris in
      Samalona were the progeny of parents from the same island, while on Barrang Lompo
      47.4% of A. ocellaris and 46.9% of A. perideraion juveniles had parents from that
      island. Self-recruitment of A. ocellaris in Barrang Lompo varied from 44% to 52%
      between the two sampling periods. The site fidelity of A. ocellaris juveniles
      that returned to their reef site in Barang Lompo was up to 44%, while for A.
      perideraion up to 19%. In Samalona, the percentage of juveniles that returned to
      their natal reef site ranged from 8% to 11%. Exchange of progeny between the two
      study islands, located 7.5 km apart, was also detected via parentage assignments.
      The larger Samalona adult population of A. ocellaris was identified as the
      parents of 21% of Barrang Lompo juveniles, while the smaller adult population on
      Barrang Lompo were the parents of only 4% of Samalona juveniles. High self
      recruitment and recruitment to nearby island reefs have important implications
      for management and conservation of anemonefishes. Small MPAs, preferably on every
      island/reef, should ensure that a part of the population is protected to enable
      replenishment by the highly localised recruitment behaviour observed in these
      species. 

PMID- 24587407
TI  - Silencing alpha-fetoprotein inhibits VEGF and MMP-2/9 production in human
      hepatocellular carcinoma cell.
AB  - Alpha-fetoprotein not only serves as a diagnostic marker for liver cancer, but
      also posses a variety of biological functions. However, the role of Alpha
      fetoprotein on tumor angiogenesis and cell invasion remains incompletely
      understood. In this study, we aimed to evaluate if Alpha-fetoprotein can regulate
      the major angiogenic factors and matrix metalloproteinases in human liver cancer
      cells. Alpha-fetoprotein silencing was achieved by Stealth RNAi. Expression of
      Alpha-fetoprotein was examined by a full-automatic electrochemistry luminescence
      immunity analyzer. Expression of VEGF, VEGFR-2, MMP-9, and MMP-2 was examined by
      Western blot and immunocytochemistry. Apoptosis was detected by TUNEL assay.
      Angiogenesis was detected by in vitro angiogenesis assay kit. Silencing of Alpha
      fetoprotein led to an increased apoptosis, which was associated with a decreased
      expression of vascular endothelial growth factor, vascular endothelial growth
      factor receptor 2, matrix metalloproteinases-2/9. These results suggest that
      Alpha-fetoprotein may play a regulatory role on angiogenesis and cell invasion
      during liver cancer development. 

PMID- 24587408
TI  - Pupil response and the subliminal mere exposure effect.
AB  - The subliminal mere exposure effect (SMEE) is the phenomenon wherein people tend
      to prefer patterns they have repeatedly observed without consciously identifying
      them. One popular explanation for the SMEE is that perceptual fluency within
      exposed patterns is misattributed to a feeling of preference for those patterns.
      Assuming that perceptual fluency is negatively correlated with the amount of
      mental effort needed to analyze perceptual aspects of incoming stimuli, pupil
      diameter should associate with SMEE strength since the former is known to reflect
      mental effort. To examine this hypothesis, we measured participants' pupil
      diameter during exposure to subthreshold stimuli. Following exposure, a
      preference test was administered. Average pupil diameter throughout exposure was
      smaller when the SMEE was induced than when the SMEE was not induced. This
      supports the hypothesis that increasing perceptual fluency during mere exposure
      modulates autonomic nervous responses, such as pupil diameter, and eventually
      leads to preference. 

PMID- 24587409
TI  - The potential therapeutic effect of guanosine after cortical focal ischemia in
      rats.
AB  - BACKGROUND AND PURPOSE: Stroke is a devastating disease. Both excitotoxicity and
      oxidative stress play important roles in ischemic brain injury, along with
      harmful impacts on ischemic cerebral tissue. As guanosine plays an important
      neuroprotective role in the central nervous system, the purpose of this study was
      to evaluate the neuroprotective effects of guanosine and putative cerebral events
      following the onset of permanent focal cerebral ischemia. METHODS: Permanent
      focal cerebral ischemia was induced in rats by thermocoagulation. Guanosine was
      administered immediately, 1 h, 3 h and 6 h after surgery. Behavioral performance
      was evaluated by cylinder testing for a period of 15 days after surgery. Brain
      oxidative stress parameters, including levels of ROS/RNS, lipid peroxidation,
      antioxidant non-enzymatic levels (GSH, vitamin C) and enzymatic parameters (SOD
      expression and activity and CAT activity), as well as glutamatergic parameters
      (EAAC1, GLAST and GLT1, glutamine synthetase) were analyzed. RESULTS: After 24 h,
      ischemic injury resulted in impaired function of the forelimb, caused brain
      infarct and increased lipid peroxidation. Treatment with guanosine restored these
      parameters. Oxidative stress markers were affected by ischemic insult,
      demonstrated by increased ROS/RNS levels, increased SOD expression with reduced
      SOD activity and decreased non-enzymatic (GSH and vitamin C) antioxidant
      defenses. Guanosine prevented increased ROS/RNS levels, decreased SOD activity,
      further increased SOD expression, increased CAT activity and restored vitamin C
      levels. Ischemia also affected glutamatergic parameters, illustrated by increased
      EAAC1 levels and decreased GLT1 levels; guanosine reversed the decreased GLT1
      levels and did not affect the EAAC1 levels. CONCLUSION: The effects of brain
      ischemia were strongly attenuated by guanosine administration. The cellular
      mechanisms involved in redox and glutamatergic homeostasis, which were both
      affected by the ischemic insult, were also modulated by guanosine. These
      observations reveal that guanosine may represent a potential therapeutic agent in
      cerebral ischemia by preventing oxidative stress and excitotoxicity.

PMID- 24587410
TI  - Astrocytic mitochondrial membrane hyperpolarization following extended oxygen and
      glucose deprivation.
AB  - Astrocytes can tolerate longer periods of oxygen and glucose deprivation (OGD) as
      compared to neurons. The reasons for this reduced vulnerability are not well
      understood. Particularly, changes in mitochondrial membrane potential
      (Deltapsi(m)) in astrocytes, an indicator of the cellular redox state, have not
      been investigated during reperfusion after extended OGD exposure. Here, we
      subjected primary mouse astrocytes to glucose deprivation (GD), OGD and
      combinations of both conditions varying in duration and sequence. Changes in
      Deltapsi(m), visualized by change in the fluorescence of JC-1, were investigated
      within one hour after reconstitution of oxygen and glucose supply, intended to
      model in vivo reperfusion. In all experiments, astrocytes showed resilience to
      extended periods of OGD, which had little effect on Deltapsi(m) during
      reperfusion, whereas GD caused a robust Deltapsi(m) negativation. In case no
      Deltapsi(m) negativation was observed after OGD, subsequent chemical oxygen
      deprivation (OD) induced by sodium azide caused depolarization, which, however,
      was significantly delayed as compared to normoxic group. When GD preceded OD for
      12 h, Deltapsi(m) hyperpolarization was induced by both GD and subsequent OD, but
      significant interaction between these conditions was not detected. However, when
      GD was extended to 48 h preceding OGD, hyperpolarization enhanced during
      reperfusion. This implicates synergistic effects of both conditions in that
      sequence. These findings provide novel information regarding the role of the two
      main substrates of electron transport chain (glucose and oxygen) and their
      hyperpolarizing effect on Deltapsi(m) during substrate deprivation, thus shedding
      new light on mechanisms of astrocyte resilience to prolonged ischemic injury.

PMID- 24587411
TI  - Luteolin inhibits human keratinocyte activation and decreases NF-kappaB induction
      that is increased in psoriatic skin.
AB  - Psoriasis (Ps) is an autoimmune disease characterized by keratinocyte
      hyperproliferation and chronic inflammation, with increased expression of tumor
      necrosis factor (TNF) and vascular endothelial growth factor (VEGF). Anti-TNF
      biologic agents are effective in treating Ps, but are associated with increased
      risk of infections and blood malignancies. Moreover, keratinocyte
      hyperproliferation and activation have yet to be addressed. Flavonoids, such as
      luteolin, are natural compounds with potent anti-inflammatory properties, but
      their actions on keratinocytes remain unknown. We show that TNF (50 ng/mL)
      triggers significant production of inflammatory mediators interleukin-6,
      interleukin-8 and VEGF from both human HaCaT and primary keratinocytes.
      Pretreatment with the flavonoid luteolin (10-100 uM) significantly inhibits mRNA
      expression and release of all three mediators in a concentration-dependent
      manner. More importantly, luteolin decreases TNF-induced phosphorylation, nuclear
      translocation and DNA binding of the nuclear factor-kappa B (NF-kappaB) typically
      involved in inflammatory mediator transcription. We also report that luteolin
      reduces TNF-induced mRNA expression of two genes (NFKB1 and RELA) encoding two NF
      kappaB subunits (NF-kappaB p50 and NF-kappaB p65, respectively). Interestingly,
      we show that gene expression of RELA is increased in human psoriatic skin.
      Keratinocyte proliferation, which is a characteristic feature of psoriatic skin,
      is effectively reduced by luteolin in HaCaT cells, but not in primary
      keratinocytes. Finally, luteolin does not affect intracellular ATP production or
      viability. Appropriate formulations of luteolin and related flavones may be
      promising candidates to be developed into local and systemic treatments for Ps
      and other inflammatory skin diseases. 

PMID- 24587452
TI  - Indonesia: an emerging market economy beset by neglected tropical diseases
      (NTDs).

PMID- 24587412
TI  - Good vibrations--effects of whole body vibration on attention in healthy
      individuals and individuals with ADHD.
AB  - OBJECTIVES: Most of the current treatment strategies of ADHD are associated with
      a number of disadvantages which strengthen the need for alternative or additional
      approaches for the treatment of ADHD. In this respect, Whole Body Vibration (WBV)
      might be interesting as it was found to have beneficial effects on a variety of
      physiological measures. The present study explored the effects of WBV on
      attention of healthy individuals and adults diagnosed with ADHD. METHODS: Eighty
      three healthy individuals and seventeen adults diagnosed with ADHD participated
      in the study. WBV treatment was applied passively, while participants were
      sitting on a chair which was mounted on a vibrating platform. A repeated measure
      design was employed in order to explore potential effects of WBV treatment on
      attention within subjects. Attention (i.e. inhibitory control) was measured with
      a color-word interference paradigm. RESULTS: A period of two minutes of WBV
      treatment had significant beneficial effects of small to medium size on attention
      of both healthy individuals and adults with ADHD. The effect of WBV treatment on
      attention did not differ significantly between groups. CONCLUSIONS: WBV was
      demonstrated to improve cognitive performance of healthy individuals as well as
      of individuals with ADHD. WBV treatment is relatively inexpensive and easy to
      apply and might therefore be of potential relevance for clinical use. The
      application of WBV treatment as a cognitive enhancement strategy and as a
      potential treatment of cognitive impairments is discussed.

PMID- 24587453
TI  - Resource planning for neglected tropical disease (NTD) control programs:
      feasibility study of the Tool for Integrated Planning and Costing (TIPAC).

PMID- 24587454
TI  - Detection of four dengue serotypes suggests rise in hyperendemicity in urban
      centers of Brazil.

PMID- 24587455
TI  - A polarized cell model for Chikungunya virus infection: entry and egress of virus
      occurs at the apical domain of polarized cells.
AB  - Chikungunya virus (CHIKV) has resulted in several outbreaks in the past six
      decades. The clinical symptoms of Chikungunya infection include fever, skin rash,
      arthralgia, and an increasing incidence of encephalitis. The re-emergence of
      CHIKV with more severe pathogenesis highlights its potential threat on our human
      health. In this study, polarized HBMEC, polarized Vero C1008 and non-polarized
      Vero cells grown on cell culture inserts were infected with CHIKV apically or
      basolaterally. Plaque assays, viral binding assays and immunofluorescence assays
      demonstrated apical entry and release of CHIKV in polarized HBMEC and Vero C1008.
      Drug treatment studies were performed to elucidate both host cell and viral
      factors involved in the sorting and release of CHIKV at the apical domain of
      polarized cells. Disruption of host cell myosin II, microtubule and microfilament
      networks did not disrupt the polarized release of CHIKV. However, treatment with
      tunicamycin resulted in a bi-directional release of CHIKV, suggesting that N
      glycans of CHIKV envelope glycoproteins could serve as apical sorting signals. 

PMID- 24587456
TI  - Significantly lower anti-Leishmania IgG responses in Sudanese versus Indian
      visceral leishmaniasis.
AB  - BACKGROUND: Visceral leishmaniasis (VL), a widely distributed systemic disease
      caused by infection with the Leishmania donovani complex (L. donovani and L.
      infantum), is almost always fatal if symptomatic and untreated. A rapid point-of
      care diagnostic test for anti-Leishmania antibodies, the rK39
      immunochromatographic test (rK39-ICT), has high sensitivity and specificity in
      South Asia but is less sensitive in East Africa. One of the underlying reasons
      may be continent-specific molecular diversity in the rK39 antigen within the L.
      donovani complex. However, a second reason may be differences in specific IgG
      anti-Leishmania levels in patients from different geographical regions, either
      due to variable antigenicity or immunological response. METHODOLOGY/PRINCIPAL
      FINDINGS: We determined IgG titres of Indian and Sudanese VL patients against
      whole cell lysates of Indian and Sudanese L. donovani strains. Indian VL patients
      had significantly higher IgG titres against both L. donovani strains compared to
      Sudanese VL patients (p<0.0001). Mean reciprocal log10 50% end-point titres
      (1/log10t50) were i) 3.80 and 3.88 for Indian plasma and ii) 2.13 and 2.09 for
      Sudanese plasma against Indian and Sudanese antigen respectively (p<0.0001).
      Overall, the Indian VL patients therefore showed a 46.8-61.7 -fold higher mean
      ELISA titre than the Sudanese VL patients. The higher IgG titres occurred in
      children (<16 years old) and adults of either sex from India (mean 1/log10t50:
      3.60-4.15) versus Sudan (mean 1/log10t50: 1.88-2.54). The greatest difference in
      IgG responses was between male Indian and Sudanese VL patients of >= 16 years old
      (mean 1/log10t50: 4.15 versus 1.99 = 144-fold (p<0.0001).
      CONCLUSIONS/SIGNIFICANCE: Anti-Leishmania IgG responses among VL patients in
      Sudan were significantly lower than in India; this may be due to chronic
      malnutrition with Zn(2+) deficiency, or variable antigenicity and capacity to
      generate IgG responses to Leishmania antigens. Such differential anti-Leishmania
      IgG levels may contribute to lower sensitivity of the rK39-ICT in East Africa.

PMID- 24587457
TI  - A multi-species bait for Chagas disease vectors.
AB  - BACKGROUND: Triatomine bugs are the insect vectors of Trypanosoma cruzi, the
      etiological agent of Chagas disease. These insects are known to aggregate inside
      shelters during daylight hours and it has been demonstrated that within shelters,
      the aggregation is induced by volatiles emitted from bug feces. These signals
      promote inter-species aggregation among most species studied, but the chemical
      composition is unknown. METHODOLOGY/PRINCIPAL FINDINGS: In the present work,
      feces from larvae of the three species were obtained and volatile compounds were
      identified by solid phase microextraction-gas chromatography-mass spectrometry
      (SPME-GC-MS). We identified five compounds, all present in feces of all of the
      three species: Triatoma infestans, Panstrongylus megistus and Triatoma
      brasiliensis. These substances were tested for attractivity and ability to
      recruit insects into shelters. Behaviorally active doses of the five substances
      were obtained for all three triatomine species. The bugs were significantly
      attracted to shelters baited with blends of 160 ng or 1.6 ug of each substance.
      CONCLUSIONS/SIGNIFICANCE: Common compounds were found in the feces of vectors of
      Chagas disease that actively recruited insects into shelters, which suggests that
      this blend of compounds could be used for the development of baits for early
      detection of reinfestation with triatomine bugs.

PMID- 24587458
TI  - Immunoepidemiological profiling of onchocerciasis patients reveals associations
      with microfilaria loads and ivermectin intake on both individual and community
      levels.
AB  - Mass drug administration (MDA) programmes against Onchocerca volvulus use
      ivermectin (IVM) which targets microfilariae (MF), the worm's offspring. Most
      infected individuals are hyporesponsive and present regulated immune responses
      despite high parasite burden. Recently, with MDA programmes, the existence of
      amicrofilaridermic (a-MF) individuals has become apparent but little is known
      about their immune responses. Within this immunoepidemiological study, we
      compared parasitology, pathology and immune profiles in infection-free volunteers
      and infected individuals that were MF(+) or a-MF. The latter stemmed from
      villages in either Central or Ashanti regions of Ghana which, at the time of the
      study, had received up to eight or only one round of MDA respectively.
      Interestingly, a-MF patients had fewer nodules and decreased IL-10 responses to
      all tested stimuli. On the other hand, this patient group displayed contrary IL-5
      profiles following in vitro stimulation or in plasma and the dampened response in
      the latter correlated to reduced eosinophils and associated factors but elevated
      neutrophils. Furthermore, multivariable regression analysis with covariates MF,
      IVM or the region (Central vs. Ashanti) revealed that immune responses were
      associated with different covariates: whereas O. volvulus-specific IL-5 responses
      were primarily associated with MF, IL-10 secretion had a negative correlation
      with times of individual IVM therapy (IIT). All plasma parameters (eosinophil
      cationic protein, IL-5, eosinophils and neutrophils) were highly associated with
      MF. With regards to IL-17 secretion, although no differences were observed
      between the groups to filarial-specific or bystander stimuli, these responses
      were highly associated with the region. These data indicate that immune responses
      are affected by both, IIT and the rounds of IVM MDA within the community.
      Consequently, it appears that a lowered infection pressure due to IVM MDA may
      affect the immune profile of community members even if they have not regularly
      participated in the programmes.

PMID- 24587459
TI  - Limited dengue virus replication in field-collected Aedes aegypti mosquitoes
      infected with Wolbachia.
AB  - INTRODUCTION: Dengue is one of the most widespread mosquito-borne diseases in the
      world. The causative agent, dengue virus (DENV), is primarily transmitted by the
      mosquito Aedes aegypti, a species that has proved difficult to control using
      conventional methods. The discovery that A. aegypti transinfected with the wMel
      strain of Wolbachia showed limited DENV replication led to trial field releases
      of these mosquitoes in Cairns, Australia as a biocontrol strategy for the virus.
      METHODOLOGY/PRINCIPAL FINDINGS: Field collected wMel mosquitoes that were
      challenged with three DENV serotypes displayed limited rates of body infection,
      viral replication and dissemination to the head compared to uninfected controls.
      Rates of dengue infection, replication and dissemination in field wMel mosquitoes
      were similar to those observed in the original transinfected wMel line that had
      been maintained in the laboratory. We found that wMel was distributed in similar
      body tissues in field mosquitoes as in laboratory ones, but, at seven days
      following blood-feeding, wMel densities increased to a greater extent in field
      mosquitoes. CONCLUSIONS/SIGNIFICANCE: Our results indicate that virus-blocking is
      likely to persist in Wolbachia-infected mosquitoes after their release and
      establishment in wild populations, suggesting that Wolbachia biocontrol may be a
      successful strategy for reducing dengue transmission in the field.

PMID- 24587460
TI  - Efficacy of cyclooctadepsipeptides and aminophenylamidines against larval,
      immature and mature adult stages of a parasitologically characterized trichurosis
      model in mice.
AB  - BACKGROUND: The genus Trichuris includes parasites of major relevance in
      veterinary and human medicine. Despite serious economic losses and enormous
      impact on public health, treatment options against whipworms are very limited.
      Additionally, there is an obvious lack of appropriately characterized
      experimental infection models. Therefore, a detailed parasitological
      characterization of a Trichuris muris isolate was performed in C57BL/10 mice.
      Subsequently, the in vivo efficacies of the aminophenylamidines amidantel,
      deacylated amidantel (dAMD) and tribendimidine as well as the
      cyclooctadepsipeptides emodepside and in particular PF1022A were analyzed. This
      was performed using various administration routes and treatment schemes targeting
      histotropic and further developed larval as well as immature and mature adult
      stages. METHODOLOGY/PRINCIPAL FINDINGS: Duration of prepatent period, time
      dependent localization of larvae during period of prepatency as well as the
      duration of patency of the infection were determined before drugs were tested in
      the characterized trichurosis model. Amidantel showed no effect against mature
      adult T. muris. Tribendimidine showed significantly higher potency than dAMD
      after oral treatments (ED50 values of 6.5 vs. 15.1 mg/kg). However, the opposite
      was found for intraperitoneal treatments (ED50 values of 15.3 vs. 8.3 mg/kg).
      When emodepside and PF1022A were compared, the latter was significantly less
      effective against mature adults following intraperitoneal (ED50 values of 6.1 vs.
      55.7 mg/kg) or subcutaneous (ED50 values of 15.2 vs. 225.7 mg/kg) administration.
      Only minimal differences were observed following oral administration (ED50 values
      of 2.7 vs. 5.2 mg/kg). Triple and most single oral doses with moderate to high
      dosages of PF1022A showed complete efficacy against histotropic second stage
      larvae (3 * 100 mg/kg or 1 * 250 mg/kg), further developed larvae (3 * 10 mg/kg
      or 1 * 100 mg/kg) and immature adults (3 * 10 mg/kg or 1*100 mg/kg). Histotropic
      first stage larvae were only eliminated after three doses of PF1022A (3 * 100
      mg/kg) but not after a single dose. CONCLUSIONS/SIGNIFICANCE: These results
      indicate that the cyclooctadepsipeptides are a drug class with promising
      candidates for further evaluation for the treatment of trichurosis of humans and
      livestock animals in single dose regimens.

PMID- 24587462
TI  - Deletion of ubiquitin fold modifier protein Ufm1 processing peptidase Ufsp in L.
      donovani abolishes Ufm1 processing and alters pathogenesis.
AB  - Previously, we showed Leishmania donovani Ufm1 has a Gly residue conserved at the
      C-terminal region with a unique 17 amino acid residue extension that must be
      processed prior to conjugation to target proteins. In this report, we describe
      for the first time the isolation and characterization of the Leishmania Ufm1
      specific protease Ufsp. Biochemical analysis of L. donovani Ufsp showed that this
      protein possesses the Ufm1 processing activity using sensitive FRET based
      activity probes. The Ufm1 cleavage activity was absent in a mutant Ufsp in which
      the active site cysteine is altered to a serine. To examine the effects of
      abolition of Ufm1 processing activity, we generated a L. donovani null mutant of
      Ufsp (LdUfsp(-/-)). Ufm1 processing activity was abolished in LdUfsp(-/-) mutant,
      and the processing defect was reversed by re-expression of wild type but not the
      cys>ser mutant in the LdUfsp(-/-) parasites. Further LdUfsp(-/-) mutants showed
      reduced survival as amastigotes in infected human macrophages but not as
      promastigotes. This growth defect in the amastigotes was reversed by re
      expression of wild type but not the cys>ser mutant in the Ufsp(-/-) indicating
      the essential nature of this protease for Leishmania pathogenesis. Further, mouse
      infection experiments showed deletion of Ufsp results in reduced virulence of the
      parasites. Additionally, Ufsp activity was inhibited by an anti-leishmanial drug
      Amphotericin B. These studies provide an opportunity to test LdUfsp(-/-)
      parasites as drug and vaccine targets. 

PMID- 24587461
TI  - Parasite-derived microRNAs in host serum as novel biomarkers of helminth
      infection.
AB  - BACKGROUND: MicroRNAs (miRNAs) are a class of short non-coding RNA that play
      important roles in disease processes in animals and are present in a highly
      stable cell-free form in body fluids. Here, we examine the capacity of host and
      parasite miRNAs to serve as tissue or serum biomarkers of Schistosoma mansoni
      infection. METHODS/PRINCIPAL FINDINGS: We used Exiqon miRNA microarrays to
      profile miRNA expression in the livers of mice infected with S. mansoni at 7
      weeks post-infection. Thirty-three mouse miRNAs were differentially expressed in
      infected compared to naive mice (>2 fold change, p<0.05) including miR-199a-3p,
      miR-199a-5p, miR-214 and miR-21, which have previously been associated with liver
      fibrosis in other settings. Five of the mouse miRNAs were also significantly
      elevated in serum by twelve weeks post-infection. Sequencing of small RNAs from
      serum confirmed the presence of these miRNAs and further revealed eleven parasite
      derived miRNAs that were detectable by eight weeks post infection. Analysis of
      host and parasite miRNA abundance by qRT-PCR was extended to serum of patients
      from low and high infection sites in Zimbabwe and Uganda. The host-derived miRNAs
      failed to distinguish uninfected from infected individuals. However, analysis of
      three of the parasite-derived miRNAs (miR-277, miR-3479-3p and bantam) could
      detect infected individuals from low and high infection intensity sites with
      specificity/sensitivity values of 89%/80% and 80%/90%, respectively. CONCLUSIONS:
      This work identifies parasite-derived miRNAs as novel markers of S. mansoni
      infection in both mice and humans, with the potential to be used with existing
      techniques to improve S. mansoni diagnosis. In contrast, although host miRNAs are
      differentially expressed in the liver during infection their abundance levels in
      serum are variable in human patients and may be useful in cases of extreme
      pathology but likely hold limited value for detecting prevalence of infection.

PMID- 24587464
TI  - Predictive value of proteinuria in adult dengue severity.
AB  - BACKGROUND: Dengue is an important viral infection with different presentations.
      Predicting disease severity is important in triaging patients requiring hospital
      care. We aim to study the value of proteinuria in predicting the development of
      dengue hemorrhagic fever (DHF), utility of urine dipstick test as a rapid
      prognostic tool. METHODOLOGY AND PRINCIPAL FINDINGS: Adult patients with
      undifferentiated fever (n = 293) were prospectively enrolled at the Infectious
      Disease Research Clinic at Tan Tock Seng Hospital, Singapore from January to
      August 2012. Dengue infection was confirmed in 168 (57%) by dengue RT-PCR or NS1
      antigen detection. Dengue cases had median fever duration of 6 days at
      enrollment. DHF was diagnosed in 34 cases according to the WHO 1997 guideline.
      Dengue fever (DF) patients were predominantly younger and were mostly seen in the
      outpatient setting with higher platelet level. Compared to DF, DHF cases had
      significantly higher peak urine protein creatinine ratio (UPCR) during clinical
      course (26 vs. 40 mg/mmol; p<0.001). We obtained a UPCR cut-off value of 29
      mg/mmol based on maximum AUC in ROC curves of peak UPCR for DF versus DHF,
      corresponding to 76% sensitivity and 60% specificity. Multivariate analysis with
      other readily available clinical and laboratory variables increased the AUC to
      0.91 with 92% sensitivity and 80% specificity. Neither urine dipstick at initial
      presentation nor peak urine dipstick value during the entire illness was able to
      discriminate between DF and DHF. CONCLUSIONS: Proteinuria measured by a
      laboratory-based UPCR test may be sensitive and specific in prognosticating adult
      dengue patients.

PMID- 24587465
TI  - Evaluation of Internet-based dengue query data: Google Dengue Trends.
AB  - Dengue is a common and growing problem worldwide, with an estimated 70-140
      million cases per year. Traditional, healthcare-based, government-implemented
      dengue surveillance is resource intensive and slow. As global Internet use has
      increased, novel, Internet-based disease monitoring tools have emerged. Google
      Dengue Trends (GDT) uses near real-time search query data to create an index of
      dengue incidence that is a linear proxy for traditional surveillance. Studies
      have shown that GDT correlates highly with dengue incidence in multiple countries
      on a large spatial scale. This study addresses the heterogeneity of GDT at
      smaller spatial scales, assessing its accuracy at the state-level in Mexico and
      identifying factors that are associated with its accuracy. We used Pearson
      correlation to estimate the association between GDT and traditional dengue
      surveillance data for Mexico at the national level and for 17 Mexican states.
      Nationally, GDT captured approximately 83% of the variability in reported cases
      over the 9 study years. The correlation between GDT and reported cases varied
      from state to state, capturing anywhere from 1% of the variability in Baja
      California to 88% in Chiapas, with higher accuracy in states with higher dengue
      average annual incidence. A model including annual average maximum temperature,
      precipitation, and their interaction accounted for 81% of the variability in GDT
      accuracy between states. This climate model was the best indicator of GDT
      accuracy, suggesting that GDT works best in areas with intense transmission,
      particularly where local climate is well suited for transmission. Internet
      accessibility (average ~ 36%) did not appear to affect GDT accuracy. While GDT
      seems to be a less robust indicator of local transmission in areas of low
      incidence and unfavorable climate, it may indicate cases among travelers in those
      areas. Identifying the strengths and limitations of novel surveillance is
      critical for these types of data to be used to make public health decisions and
      forecasting models.

PMID- 24587463
TI  - Comparative analysis of salivary gland transcriptomes of Phlebotomus orientalis
      sand flies from endemic and non-endemic foci of visceral leishmaniasis.
AB  - BACKGROUND: In East Africa, Phlebotomus orientalis serves as the main vector of
      Leishmania donovani, the causative agent of visceral leishmaniasis (VL).
      Phlebotomus orientalis is present at two distant localities in Ethiopia; Addis
      Zemen where VL is endemic and Melka Werer where transmission of VL does not
      occur. To find out whether the difference in epidemiology of VL is due to distant
      compositions of P. orientalis saliva we established colonies from Addis Zemen and
      Melka Werer, analyzed and compared the transcriptomes, proteomes and enzymatic
      activity of the salivary glands. METHODOLOGY/PRINCIPAL FINDINGS: Two cDNA
      libraries were constructed from the female salivary glands of P. orientalis from
      Addis Zemen and Melka Werer. Clones of each P. orientalis library were randomly
      selected, sequenced and analyzed. In P. orientalis transcriptomes, we identified
      members of 13 main protein families. Phylogenetic analysis and multiple sequence
      alignments were performed to evaluate differences between the P. orientalis
      colonies and to show the relationship with other sand fly species from the
      subgenus Larroussius. To further compare both colonies, we investigated the
      humoral antigenicity and cross-reactivity of the salivary proteins and the
      activity of salivary apyrase and hyaluronidase. CONCLUSIONS: This is the first
      report of the salivary components of P. orientalis, an important vector sand fly.
      Our study expanded the knowledge of salivary gland compounds of sand fly species
      in the subgenus Larroussius. Based on the phylogenetic analysis, we showed that
      P. orientalis is closely related to Phlebotomus tobbi and Phlebotomus
      perniciosus, whereas Phlebotomus ariasi is evolutionarily more distinct species.
      We also demonstrated that there is no significant difference between the
      transcriptomes, proteomes or enzymatic properties of the salivary components of
      Addis Zemen (endemic area) and Melka Werer (non-endemic area) P. orientalis
      colonies. Thus, the different epidemiology of VL in these Ethiopian foci cannot
      be attributed to the salivary gland composition.

PMID- 24587466
TI  - Mapping the geographical distribution of lymphatic filariasis in Zambia.
AB  - BACKGROUND: Past case reports have indicated that lymphatic filariasis (LF)
      occurs in Zambia, but knowledge about its geographical distribution and
      prevalence pattern, and the underlying potential environmental drivers, has been
      limited. As a background for planning and implementation of control, a country
      wide mapping survey was undertaken between 2003 and 2011. Here the mapping
      activities are outlined, the findings across the numerous survey sites are
      presented, and the ecological requirements of the LF distribution are explored.
      METHODOLOGY/PRINCIPAL FINDINGS: Approximately 10,000 adult volunteers from 108
      geo-referenced survey sites across Zambia were examined for circulating filarial
      antigens (CFA) with rapid format ICT cards, and a map indicating the distribution
      of CFA prevalences in Zambia was prepared. 78% of survey sites had CFA positive
      cases, with prevalences ranging between 1% and 54%. Most positive survey sites
      had low prevalence, but six foci with more than 15% prevalence were identified.
      The observed geographical variation in prevalence pattern was examined in more
      detail using a species distribution modeling approach to explore environmental
      requirements for parasite presence, and to predict potential suitable habitats
      over unsurveyed areas. Of note, areas associated with human modification of the
      landscape appeared to play an important role for the general presence of LF,
      whereas temperature (measured as averaged seasonal land surface temperature)
      seemed to be an important determinant of medium-high prevalence levels.
      CONCLUSIONS/SIGNIFICANCE: LF was found to be surprisingly widespread in Zambia,
      although in most places with low prevalence. The produced maps and the identified
      environmental correlates of LF infection will provide useful guidance for
      planning and start-up of geographically targeted and cost-effective LF control in
      Zambia.

PMID- 24587467
TI  - Comparison of three quality of life instruments in lymphatic filariasis: DLQI,
      WHODAS 2.0, and LFSQQ.
AB  - BACKGROUND: The Global Program to Eliminate Lymphatic Filariasis aims to
      interrupt transmission of lymphatic filariasis and manage morbidity in people
      currently living with the disease. A component of morbidity management is
      improving health-related quality of life (HRQoL) in patients. Measurement of
      HRQoL in current management programs is varied because of the lack of a standard
      HRQoL tool for use in the lymphatic filariasis population. METHODOLOGY/PRINCIPAL
      FINDINGS: In this study, the psychometric properties of three health status
      measures were compared when used in a group of lymphatic filariasis patients and
      healthy controls. The World Health Organization Disability Assessment Schedule
      2.0 (WHODAS 2.0), the Dermatology Life Quality Index (DLQI), and the Lymphatic
      Filariasis Quality of Life Questionnaire (LFSQQ) were administered to 36 stage II
      and stage III lymphatic filariasis subjects and 36 age and sex matched controls
      in Kerala, India. All three tools yielded missing value rates lower than 10%,
      suggesting high feasibility. Highest internal consistency was seen in the LFSQQ
      (alpha = 0.97). Discriminant validity analysis demonstrated that HRQoL was
      significantly lower in the LF group than in controls for the WHODAS 2.0, DLQI,
      and LFSQQ, but total HRQoL scores did not differ between stage II and stage III
      lymphedema subjects. The LFSQQ total score correlated most strongly with the
      WHODAS 2.0 (r = 0.91, p<0.001) and DLQI (r = 0.81, p<0.001).
      CONCLUSIONS/SIGNIFICANCE: The WHODAS 2.0, DLQI, and LFSQQ demonstrate acceptable
      feasibility, internal consistency, discriminate validity, and construct validity.
      Based on our psychometric analyses, the LFSQQ performs the best and is
      recommended for use in the lymphatic filariasis population.

PMID- 24587468
TI  - Memantine, an antagonist of the NMDA glutamate receptor, affects cell
      proliferation, differentiation and the intracellular cycle and induces apoptosis
      in Trypanosoma cruzi.
AB  - Chagas' disease is caused by the protozoan parasite Trypanosoma cruzi and affects
      approximately 10 million people in endemic areas of Mexico and Central and South
      America. Currently available chemotherapies are limited to two compounds:
      Nifurtimox and Benznidazole. Both drugs reduce the symptoms of the disease and
      mortality among infected individuals when used during the acute phase, but their
      efficacy during the chronic phase (during which the majority of cases are
      diagnosed) remains controversial. Moreover, these drugs have several side
      effects. The aim of this study was to evaluate the effect of Memantine, an
      antagonist of the glutamate receptor in the CNS of mammals, on the life cycle of
      T. cruzi. Memantine exhibited a trypanocidal effect, inhibiting the proliferation
      of epimastigotes (IC50 172.6 uM). Furthermore, this compound interfered with
      metacyclogenesis (approximately 30% reduction) and affected the energy metabolism
      of the parasite. In addition, Memantine triggered mechanisms that led to the
      apoptosis-like cell death of epimastigotes, with extracellular exposure of
      phosphatidylserine, increased production of reactive oxygen species, decreased
      ATP levels, increased intracellular Ca(2+) and morphological changes. Moreover,
      Memantine interfered with the intracellular cycle of the parasite, specifically
      the amastigote stage (IC50 31 uM). Interestingly, the stages of the parasite life
      cycle that require more energy (epimastigote and amastigote) were more affected
      as were the processes of differentiation and cell invasion. 

PMID- 24587469
TI  - Risk factors for soil-transmitted helminth infections during the first 3 years of
      life in the tropics; findings from a birth cohort.
AB  - BACKGROUND: Soil-transmitted helminths (STH) infect more than 2 billion humans
      worldwide, causing significant morbidity in children. There are few data on the
      epidemiology and risk factors for infection in pre-school children. To
      investigate risk factors for infection in early childhood, we analysed data
      prospectively collected in the ECUAVIDA birth cohort in Ecuador. METHODS AND
      FINDINGS: Children were recruited at birth and followed up to 3 years of age with
      periodic collection of stool samples that were examined microscopically for STH
      parasites. Data on social, demographic, and environmental risk factors were
      collected from the mother at time of enrollment. Associations between exposures
      and detection of STH infections were analysed by multivariable logistic
      regression. Data were analysed from 1,697 children for whom a stool sample was
      obtained at 3 years. 42.3% had at least one STH infection in the first 3 years of
      life and the most common infections were caused by A. lumbricoides (33.2% of
      children) and T. trichiura (21.2%). Hookworm infection was detected in 0.9% of
      children. Risk of STH infection was associated with factors indicative of poverty
      in our study population such as Afro-Ecuadorian ethnicity and low maternal
      educational level. Maternal STH infections during pregnancy were strong risk
      factors for any childhood STH infection, infections with either A. lumbricoides
      or T. trichiura, and early age of first STH infection. Children of mothers with
      moderate to high infections intensities with A. lumbricoides were most at risk.
      CONCLUSIONS: Our data show high rates of infection with STH parasites during the
      first 3 years of life in an Ecuadorian birth cohort, an observation that was
      strongly associated with maternal STH infections during pregnancy. The targeted
      treatment of women of childbearing age, in particular before pregnancy, with
      anthelmintic drugs could offer a novel approach to the prevention of STH
      infections in pre-school children.

PMID- 24587471
TI  - Costs analysis of a population level rabies control programme in Tamil Nadu,
      India.
AB  - The study aimed to determine costs to the state government of implementing
      different interventions for controlling rabies among the entire human and animal
      populations of Tamil Nadu. This built upon an earlier assessment of Tamil Nadu's
      efforts to control rabies. Anti-rabies vaccines were made available at all health
      facilities. Costs were estimated for five different combinations of animal and
      human interventions using an activity-based costing approach from the provider
      perspective. Disease and population data were sourced from the state surveillance
      data, human census and livestock census. Program costs were extrapolated from
      official documents. All capital costs were depreciated to estimate annualized
      costs. All costs were inflated to 2012 Rupees. Sensitivity analysis was conducted
      across all major cost centres to assess their relative impact on program costs.
      It was found that the annual costs of providing Anti-rabies vaccine alone and in
      combination with Immunoglobulins was $0.7 million (Rs 36 million) and $2.2
      million (Rs 119 million), respectively. For animal sector interventions, the
      annualised costs of rolling out surgical sterilisation-immunization, injectable
      immunization and oral immunizations were estimated to be $ 44 million (Rs 2,350
      million), $23 million (Rs 1,230 million) and $ 11 million (Rs 590 million),
      respectively. Dog bite incidence, health systems coverage and cost of rabies
      biologicals were found to be important drivers of costs for human interventions.
      For the animal sector interventions, the size of dog catching team, dog
      population and vaccine costs were found to be driving the costs. Rabies control
      in Tamil Nadu seems a costly proposition the way it is currently structured.
      Policy makers in Tamil Nadu and other similar settings should consider the long
      term financial sustainability before embarking upon a state or nation-wide rabies
      control programme. 

PMID- 24587470
TI  - Deliberate attenuation of chikungunya virus by adaptation to heparan sulfate
      dependent infectivity: a model for rational arboviral vaccine design.
AB  - Mosquito-borne chikungunya virus (CHIKV) is a positive-sense, single-stranded RNA
      virus from the genus Alphavirus, family Togaviridae, which causes fever, rash and
      severe persistent polyarthralgia in humans. Since there are currently no FDA
      licensed vaccines or antiviral therapies for CHIKV, the development of vaccine
      candidates is of critical importance. Historically, live-attenuated vaccines
      (LAVs) for protection against arthropod-borne viruses have been created by blind
      cell culture passage leading to attenuation of disease, while maintaining
      immunogenicity. Attenuation may occur via multiple mechanisms. However, all
      examined arbovirus LAVs have in common the acquisition of positively charged
      amino acid substitutions in cell-surface attachment proteins that render virus
      infection partially dependent upon heparan sulfate (HS), a ubiquitously expressed
      sulfated polysaccharide, and appear to attenuate by retarding dissemination of
      virus particles in vivo. We previously reported that, like other wild-type Old
      World alphaviruses, CHIKV strain, La Reunion, (CHIKV-LR), does not depend upon HS
      for infectivity. To deliberately identify CHIKV attachment protein mutations that
      could be combined with other attenuating processes in a LAV candidate, we
      passaged CHIKV-LR on evolutionarily divergent cell-types. A panel of single amino
      acid substitutions was identified in the E2 glycoprotein of passaged virus
      populations that were predicted to increase electrostatic potential. Each of
      these substitutions was made in the CHIKV-LR cDNA clone and comparisons of the
      mutant viruses revealed surface exposure of the mutated residue on the spike and
      sensitivity to competition with the HS analog, heparin, to be primary correlates
      of attenuation in vivo. Furthermore, we have identified a mutation at E2 position
      79 as a promising candidate for inclusion in a CHIKV LAV. 

PMID- 24587472
TI  - Pharmacological approaches that slow lymphatic flow as a snakebite first aid.
AB  - BACKGROUND: This study examines the use of topical pharmacological agents as a
      snakebite first aid where slowing venom reaching the circulation prevents
      systemic toxicity. It is based on the fact that toxin molecules in most snake
      venoms are large molecules and generally first enter and traverse the lymphatic
      system before accessing the circulation. It follows on from a previous study
      where it was shown that topical application of a nitric oxide donor slowed lymph
      flow to a similar extent in humans and rats as well as increased the time to
      respiratory arrest for subcutaneous injection of an elapid venom (Pseudonaja
      textilis, Ptx; Eastern brown snake) into the hind feet of anaesthetized rats.
      METHODOLOGY/PRINCIPAL FINDINGS: The effects of topical application of the L-type
      Ca(2+) channel antagonist nifedipine and the local anesthetic lignocaine in
      inhibiting lymph flow and protecting against envenomation was examined in an
      anaesthetized rat model. The agents significantly increased dye-measured lymph
      transit times by 500% and 390% compared to controls and increased the time to
      respiratory arrest to foot injection of a lethal dose of Ptx venom by 60% and 40%
      respectively. The study also examined the effect of Ptx venom dose over the
      lethal range of 0.4 to 1.5 mg/kg finding a negative linear relationship between
      increase in venom dose and time to respiratory arrest. CONCLUSIONS/SIGNIFICANCE:
      The findings suggest that a range of agents that inhibit lymphatic flow could
      potentially be used as an adjunct treatment to pressure bandaging with
      immobilization (PBI) in snakebite first aid. This is important given that PBI (a
      snakebite first aid recommended by the Australian National Health and Medical
      research Council) is often incorrectly applied. The use of a local anesthetic
      would have the added advantage of reducing pain.

PMID- 24587474
TI  - Free fatty acids to predict recurrent ischemic stroke.

PMID- 24587473
TI  - The association of parasitic infections in pregnancy and maternal and fetal
      anemia: a cohort study in coastal Kenya.
AB  - BACKGROUND: Relative contribution of these infections on anemia in pregnancy is
      not certain. While measures to protect pregnant women against malaria have been
      scaling up, interventions against helminthes have received much less attention.
      In this study, we determine the relative impact of helminthes and malaria on
      maternal anemia. METHODS: A prospective observational study was conducted in
      coastal Kenya among a cohort of pregnant women who were recruited at their first
      antenatal care (ANC) visit and tested for malaria, hookworm, and other parasitic
      infections and anemia at enrollment. All women enrolled in the study received
      presumptive treatment with sulfadoxine-pyrimethamine, iron and multi-vitamins and
      women diagnosed with helminthic infections were treated with albendazole. Women
      delivering a live, term birth, were also tested for maternal anemia, fetal anemia
      and presence of infection at delivery. PRINCIPAL FINDINGS: Of the 706 women
      studied, at the first ANC visit, 27% had moderate/severe anemia and 71% of women
      were anemic overall. The infections with highest prevalence were hookworm (24%),
      urogenital schistosomiasis (17%), trichuria (10%), and malaria (9%). In adjusted
      and unadjusted analyses, moderate/severe anemia at first ANC visit was associated
      with the higher intensities of hookworm and P. falciparum microscopy-malaria
      infections. At delivery, 34% of women had moderate/severe anemia and 18% of
      infants' cord hemoglobin was consistent with fetal anemia. While none of the
      maternal infections were significantly associated with fetal anemia,
      moderate/severe maternal anemia was associated with fetal anemia. CONCLUSIONS:
      More than one quarter of women receiving standard ANC with IPTp for malaria had
      moderate/severe anemia in pregnancy and high rates of parasitic infection. Thus,
      addressing the role of co-infections, such as hookworm, as well as under
      nutrition, and their contribution to anemia is needed.

PMID- 24587475
TI  - Untargeted 1H-NMR metabolomics in CSF: toward a diagnostic biomarker for motor
      neuron disease.
AB  - OBJECTIVES: To develop a CSF metabolomics signature for motor neuron disease
      (MND) using (1)H-NMR spectroscopy and to evaluate the predictive value of the
      profile in a separate cohort. METHODS: We collected CSF from patients with MND
      and controls and analyzed the samples using (1)H-NMR spectroscopy. We divided the
      total patient sample in a 4:1 ratio into a training cohort and a test cohort.
      First, a metabolomics signature was created by statistical modeling in the
      training cohort, and then the analyses tested the predictive value of the
      signature in the test cohort. We conducted 10 independent trials for each step.
      Finally, we identified the compounds that contributed most consistently to the
      metabolome profile. RESULTS: Analysis of CSF from 95 patients and 86 controls
      identified a diagnostic profile for MND (R(2)X > 22%, R(2)Y > 93%, Q(2) > 66%).
      The best model selected the correct diagnosis with mean probability of 99.31% in
      the training cohort. The profile discriminated between diagnostic groups with
      78.9% sensitivity and 76.5% specificity in the test cohort. Metabolites linked to
      pathophysiologic pathways in MND (i.e., threonine, histidine, and molecules
      related to the metabolism of branched amino acids) were among the discriminant
      compounds. CONCLUSION: CSF metabolomics using (1)H-NMR spectroscopy can detect a
      reproducible metabolic signature for MND with reasonable performance. To our
      knowledge, this is the first metabolomics study that shows that a validation in
      separate cohorts is feasible. These data should be considered in future biomarker
      studies. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that
      CSF metabolomics accurately distinguishes MNDs from other neurologic diseases.

PMID- 24587476
TI  - Hypoglossal nerve dysfunction and sleep-disordered breathing after stroke.
AB  - OBJECTIVE: This cross-sectional study of acute ischemic stroke patients examined
      relationships between hypoglossal nerve conduction, sleep-disordered breathing
      (SDB), and its severity. METHODS: Patients within 7 days of stroke underwent
      nocturnal respiratory monitoring with the ApneaLink device and hypoglossal nerve
      conduction studies. RESULTS: Eighteen of 52 subjects (35% [95% confidence
      interval: 22%, 49%]) had an abnormal hypoglossal amplitude and 23 (44% [95%
      confidence interval: 30%, 59%]) had an abnormal hypoglossal latency. No
      differences were identified in hypoglossal nerve latency or amplitude between
      those with (n = 26) and without (n = 26) significant SDB, defined by an apnea
      hypopnea index >= 15. However, hypoglossal nerve conduction latency was
      associated (linear regression p < 0.05) with SDB severity as reflected by the
      apnea-hypopnea index. CONCLUSIONS: Acute ischemic stroke patients have a high
      prevalence of hypoglossal nerve dysfunction. Further studies are needed to
      explore whether hypoglossal nerve dysfunction may be a cause or consequence of
      SDB in stroke patients and whether this association can provide further insight
      into the pathophysiology of SDB in this population.

PMID- 24587477
TI  - High free fatty acid level is associated with recurrent stroke in cardioembolic
      stroke patients.
AB  - OBJECTIVE: To determine whether the plasma level of free fatty acid (FFA) could
      be associated with recurrent stroke in cardioembolic (CE) stroke patients.
      METHODS: We analyzed data from 669 acute ischemic stroke patients and examined
      the association between FFA concentration and recurrent stroke in CE stroke
      patients compared with non-CE stroke patients. RESULTS: The baseline plasma FFA
      concentration (mEq/L) was approximately 1.5-fold higher in CE stroke patients
      (1.01 +/- 0.63) than in non-CE stroke patients (0.72 +/- 0.51). Multivariate
      logistic analysis showed that an increased level of FFA was significantly
      associated with CE stroke (hazard ratio [HR] 2.124, confidence interval [CI]
      1.492-3.024). During the mean follow-up period of 25.4 months, a total of 56
      (8.4%) patients experienced a stroke recurrence. The recurrence rate did not
      differ between patients with CE (10.5%) and non-CE (8.0%) stroke (p = 0.396). In
      CE stroke patients, an elevated baseline FFA concentration was independently
      associated with stroke recurrence (HR 2.711, CI 1.056-6.959). However, there was
      no association between FFA and stroke recurrence in non-CE stroke patients.
      CONCLUSION: In this retrospective registry-based observational study, CE stroke
      seemed to be associated with elevated plasma level of FFA. In addition, the
      present study suggested that an elevated FFA concentration could be a useful
      indicator for predicting recurrent stroke in CE stroke patients.

PMID- 24587478
TI  - Poststroke atrial fibrillation: cause or consequence? Critical review of current
      views.
AB  - Poststroke atrial fibrillation (AF) represents up to 1 of 4 overall AF cases in
      acute ischemic stroke. Current guidelines recommend oral anticoagulation for
      every ischemic stroke patient in whom AF is diagnosed. However, in some cases, AF
      detected after acute ischemic stroke may be short-lasting and perhaps a
      nonrecurrent autonomic and inflammatory epiphenomena of stroke. The autonomic
      regulation of cardiac rhythm constitutes an integrated relay system. The highest
      level of control is exerted by the cerebral cortex, particularly the insula. The
      onset of AF may be associated with an imbalance of sympathetic and
      parasympathetic activity, a common consequence of insular infarctions. This
      autonomic imbalance and an interruption in the cerebral regulation of the
      intrinsic cardiac autonomic system constitute the most likely mechanisms
      responsible for the autonomic pathway. The role of inflammation in the genesis of
      AF within the first few days after ischemic stroke may occur through inflammatory
      mediators stimulating the intrinsic autonomic system and by direct damage to
      atrial myocardium. To what extent poststroke AF is the cause or a consequence
      remains uncertain. 

PMID- 24587479
TI  - CNS inflammation other than multiple sclerosis: how likely is diagnosis?

PMID- 24587481
TI  - The order of the factors affects a product!

PMID- 24587482
TI  - Aerosol administration during nasal CPAP in newborns can be optimized.

PMID- 24587483
TI  - Pediatric extubation readiness: faith-based practice or amenable to
      standardization?

PMID- 24587484
TI  - Furosemide Nebulization in Patients With COPD Exacerbation.

PMID- 24587485
TI  - Furosemide nebulization in patients with COPD exacerbation--reply.

PMID- 24587486
TI  - Enhanced p62 expression through impaired  proteasomal degradation is involved in
      caspase-1  activation in monosodium urate crystal-induced  interleukin-1b
      expression.
AB  - OBJECTIVE: Evidence for the role of autophagy in the regulation of inflammation,
      especially IL-1b expression in response to monosodium urate (MSU) crystals, is
      presented. This study investigated the role of p62, a selective autophagy
      receptor in autophagy, in IL-1b production in MSU crystal-induced inflammation.
      METHODS: IL-1b, TNF-a and IL-6 mRNA expression was measured by quantitative real
      time PCR (qRTPCR). Autophagy-related molecules such as p62, Cullin-3, microtubule
      associated protein 1 light-chain 3 (LC3) I/II, ubiquitin, caspase-1 and mitogen
      activated protein kinase (MAPK)-related proteins were measured by immunoblotting.
      Small interfering RNAs (siRNAs) for Atg16L1, IL-1b and p62 were used to silence
      each target gene. RESULTS: MSU crystals accelerate the process of autophagosome
      formation and also induce impairment of proteasomal degradation, resulting in p62
      accumulation in autophagy. Enhanced p62 accumulation by MSU crystals leads to IL
      1b expression through activation of extracellular signal-regulated kinase (ERK)
      and c-Jun N-terminal kinase (JNK), but not p38, of the MAPK pathway and is also
      involved in activation of caspase-1 in inflammasomes. Impaired autophagosome
      formation by Atg16L1 siRNA significantly amplified p62 levels, thereby producing
      enhanced inflammatory responses, including overexpression of IL-1b under
      stimulation of MSU crystals. IL-1b also induces p62 protein, and blocking IL-1b
      under stimulation of MSU crystals greatly reduced p62 levels. CONCLUSION: This
      study demonstrates that enhanced p62 expression through impaired proteasomal
      degradation by MSU crystals plays a crucial role in caspase-1 activation in MSU
      crystal-induced IL-1b production. p62 is required for activation of inflammasomes
      during acute inflammation in gout.

PMID- 24587487
TI  - Measurement of radioactivity levels and assessment of radioactivity hazards of
      soil samples in Karaman, Turkey.
AB  - In this study, the levels of the natural and artificial radioactivity in soil
      samples collected from surrounding of Karaman in Turkey were measured. Activity
      concentrations of the concerned radionuclides were determined by gamma-ray
      spectrometry using a high-purity germanium detector with a relative efficiency of
      40 % at 1.332 MeV. The results obtained for the (238)U series ((226)Ra, (214)Pb
      and (214)Bi), (232)Th series ((228)Ac), (40)K and fission product (137)Cs are
      discussed. To evaluate the radiological hazard of radioactivity in samples, the
      radium equivalent activity (Raeq), the absorbed dose rate (D), the annual
      effective dose and the external (Hex) and internal hazard index (Hin) were
      calculated and presented in comparison with the data collected from different
      areas in the world and Turkey. 

PMID- 24587489
TI  - An International Comparison of Adolescent and Young Adult Mortality.
AB  - This paper analyzes mortality rates for 3 of the main causes of deaths between
      the ages of 15 and 34 (motor vehicle injuries, homicide, and suicide) from 1950
      to 1996, and across 26 countries. Average sex ratios and age patterns and the
      trends in age- and sex-standardized mortality rates are analyzed for each cause.
      Overall, youth violent mortality levels have been remarkably stable since the
      1950s. As mortality due to other causes has receded, the contribution of these
      three causes has increased from 25 to 40 percent between the 1950s and the mid
      1970s, and has remained above 40 percent since. Last, a principal component
      analysis is performed to summarize the variance in age-, sex-, and cause-specific
      rates over time and across countries. This summary representation of
      international differences displays regional clusters and emphasizes the
      "outlying" position of the United States among industrialized nations.

PMID- 24587490
TI  - Real-time Space-time Integration in GIScience and Geography.
AB  - Space-time integration has long been the topic of study and speculation in
      geography. However, in recent years an entirely new form of space-time
      integration has become possible in GIS and GIScience: real-time space-time
      integration and interaction. While real-time spatiotemporal data is now being
      generated almost ubiquitously, and its applications in research and commerce are
      widespread and rapidly accelerating, the ability to continuously create and
      interact with fused space-time data in geography and GIScience is a recent
      phenomenon, made possible by the invention and development of real-time
      interactive (RTI) GPS/GIS technology and functionality in the late 1980s and
      early 1990s. This innovation has since functioned as a core change agent in
      geography, cartography, GIScience and many related fields, profoundly realigning
      traditional relationships and structures, expanding research horizons, and
      transforming the ways geographic data is now collected, mapped, modeled, and
      used, both in geography and in science and society more broadly. Real-time space
      time interactive functionality remains today the underlying process generating
      the current explosion of fused spatiotemporal data, new geographic research
      initiatives, and myriad geospatial applications in governments, businesses, and
      society. This essay addresses briefly the development of these real-time space
      time functions and capabilities; their impact on geography, cartography, and
      GIScience; and some implications for how discovery and change can occur in
      geography and GIScience, and how we might foster continued innovation in these
      fields.

PMID- 24587491
TI  - Evidence-based case reports.

PMID- 24587488
TI  - Classes of phosphoinositide 3-kinases at a glance.
AB  - The phosphoinositide 3-kinase (PI3K) family is important to nearly all aspects of
      cell and tissue biology and central to human cancer, diabetes and aging. PI3Ks
      are spatially regulated and multifunctional, and together, act at nearly all
      membranes in the cell to regulate a wide range of signaling, membrane trafficking
      and metabolic processes. There is a broadening recognition of the importance of
      distinct roles for each of the three different PI3K classes (I, II and III), as
      well as for the different isoforms within each class. Ongoing issues include the
      need for a better understanding of the in vivo complexity of PI3K regulation and
      cellular functions. This Cell Science at a Glance article and the accompanying
      poster summarize the biochemical activities, cellular roles and functional
      requirements for the three classes of PI3Ks. In doing so, we aim to provide an
      overview of the parallels, the key differences and crucial interplays between the
      regulation and roles of the three PI3K classes.

PMID- 24587492
TI  - Creating a Chiropractic Practice-Based Research Network (PBRN): Enhancing the
      management of musculoskeletal care.

PMID- 24587493
TI  - Detection of syringomyelia in a pediatric patient with mild scoliosis: a case
      report.
AB  - It can be challenging to detect syringomyelia in patients with scoliosis, as some
      cases are mildly symptomatic with little to no neurological deficits. However, a
      timely diagnosis of syringomyelia is needed to facilitate important treatment
      considerations. This case report details an 11-year-old female with mild
      scoliosis and a two-year history of spinal pain that had short-term symptomatic
      relief from chiropractic treatment. Subtle neurological signs were detected only
      at re-evaluation, which prompted further investigation with radiographs and
      subsequent magnetic resonance imaging (MRI). MRI revealed a non-expansile syrinx
      measuring 3 mm at its widest diameter that extended from C5 to the conus
      medullaris. The aim of this case is to heighten awareness of the potential
      diagnostic challenges in patients with syringomyelia and scoliosis. The
      incidence, pathogenesis, clinical presentation, and management of syringomyelia
      will be presented to help primary contact providers with appropriate referral and
      co-management of these patients. 

PMID- 24587494
TI  - A comparison of quality and satisfaction experiences of patients attending
      chiropractic and physician offices in Ontario.
AB  - INTRODUCTION: Improving the quality of healthcare is a common goal of consumers,
      providers, payer groups, and governments. There is evidence that patient
      satisfaction influences the perceptions of the quality of care received. METHODS:
      This exploratory, qualitative study described and analyzed, the similarities and
      differences in satisfaction and dissatisfaction experiences of patients attending
      physicians (social justice) and chiropractors (market justice) for healthcare
      services in Niagara Region, Ontario. Using inductive content analysis the
      satisfaction and dissatisfaction experiences were themed to develop groups,
      categories, and sub-categories of quality judgments of care experiences. RESULTS:
      Study participants experienced both satisfying and dissatisfying critical
      incidents in the areas of standards of practice, professional and practice
      attributes, time management, and treatment outcomes. Cost was not a marked source
      of satisfaction or dissatisfaction. CONCLUSION: Patients may be more capable of
      generating quality judgments on the technical aspects of medical and chiropractic
      care, particularly treatment outcomes and standards of practice, than previously
      thought.

PMID- 24587495
TI  - Duplicated right crus of the diaphragm: a cadaveric case report.
AB  - The lumbar part of the diaphragm arises from the lumbar vertebrae by right and
      left crura. The duplication of crura of the diaphragm is rarely reported in the
      past. During regular dissection classes to the medical students, we came across a
      case of duplicated right crus of the diaphragm. The right crus of the diaphragm
      was duplicated completely and presented two separate crura; medial right crus &
      lateral right crus. The medial right crus was attached to the anterolateral
      surfaces of the superior three lumbar vertebral bodies and intervertebral discs
      and merged with the anterior longitudinal ligament. The lateral right crus
      attached only to the intervertebral disc between the third and fourth lumbar
      vertebrae. These two crura bordered a retrocrural space in the inferior posterior
      mediastinum. The greater and lesser splanchnic nerves entered the abdomen by
      passing through this space. No duplication was observed in the left crus. The
      muscle fibres of medial right crus contributed to the formation of the esophageal
      opening. Knowledge of variations in the diaphragmatic crural anatomy is useful in
      the diagnosis of disease processes in the retrocrural space and also might help
      while performing the surgical repair of gastroesophageal reflux disease. 

PMID- 24587496
TI  - A delayed diagnosis of bilateral facet dislocation of the cervical spine: a case
      report.
AB  - OBJECTIVE: To review the case of a patient suffering from bilateral facet
      dislocation of the cervical spine. CLINICAL FEATURES: A 53-year-old male was
      involved in a car accident and was transported to the hospital. Cervical
      radiographs were taken at the emergency department and interpreted as normal.
      Four days later, he consulted a chiropractor where radiographs of the cervical
      spine were repeated. The examination revealed bilateral cervical facet joint
      dislocation at C5-C6 as well as a fracture involving the spinous process and
      laminae of C6. INTERVENTION AND OUTCOME: The patient was referred to the hospital
      and underwent surgery. CONCLUSION: Patients involved in motor vehicle accidents
      often consult chiropractors for neck pain treatment. A high index of suspicion
      due to significant history and physical examination findings should guide the
      clinician in determining the need for reviewing the initial radiographs (if taken
      and available) or request repeat studies, regardless of the initial imaging
      status.

PMID- 24587497
TI  - Chiropractic management of elbow tendinopathy following a sports related trauma.
AB  - OBJECTIVE: This report describes chiropractic management of a case of sub-acute
      elbow pain and swelling with Active Release Technique(r) and acupuncture. CASE
      PRESENTATION: A 41-year-old male presented to a chiropractic clinic with a
      primary complaint of elbow pain and swelling following a fall while playing
      basketball five weeks prior. INTERVENTION AND OUTCOME: Treatment consisted of two
      sessions of needle acupuncture and one treatment of Active Release Techniques(r)
      (ART) applied to the left elbow region. CONCLUSIONS: The patient's outcomes
      indicated a quick resolution of subjective complaints and objective findings with
      the chosen treatment. Further research is needed to demonstrate safety, clinical
      effectiveness, and cost effectiveness when compared to other treatments.

PMID- 24587498
TI  - Financial attitudes, knowledge, and habits of chiropractic students: A
      descriptive survey.
AB  - OBJECTIVE: Our purpose was to describe the financial knowledge, habits and
      attitudes of chiropractic students. METHODS: We designed a cross-sectional survey
      to measure basic financial knowledge, current financial habits, risk tolerance,
      and beliefs about future income among 250 students enrolled in business courses
      at one US chiropractic college. Descriptive statistical analyses were performed.
      RESULTS: We received 57 questionnaires (23% response rate). Most respondents
      would accumulate over $125,000 in student loan debt by graduation. Financial
      knowledge was low (mean 77%). Most respondents (72%) scored as average financial
      risk takers. Chiropractic students reported recommended short-term habits such as
      having checking accounts (90%) and health insurance (63%) or paying monthly bills
      (88%) and credit cards (60%). Few saved money for unplanned expenses (39%) or
      long-term goals (26%), kept written budgets (32%), or had retirement accounts
      (19%). CONCLUSION: These chiropractic students demonstrated inadequate financial
      literacy and did not engage in many recommended financial habits.

PMID- 24587499
TI  - Ross E. Baker, DC: A Canadian chiropractic survivor.
AB  - This paper is an historical biography of a fortunate man. It begins with a
      glimpse of Ross E. Baker's origins in south-western Ontario, watches him going to
      school and working in Hamilton before joining the Canadian Army and shipping off
      to Europe to fight in the Second World War. At War's end, the article picks up
      Dr. Baker as he comes home, starts a family, becomes a chiropractor and sustains
      a viable practice. Now in the twilight of life, the good doctor is last seen
      content with his retirement, spending days at his cottage property, reviewing his
      memoirs and reflecting on the tumult, terror and eventual triumph of the D-Day
      landing at Normandy. 

PMID- 24587500
TI  - Conservative management of idiopathic anterior atlantoaxial subluxation without
      neurological deficits in an 83-year-old female: A case report.
AB  - Atlantoaxial subluxation that is not related to traumatic, congenital, or
      rheumatological conditions is rare and can be a diagnostic challenge. This case
      report details a case of anterior atlantoaxial subluxation in an 83-year-old
      female without history of trauma, congenital, or rheumatological conditions. She
      presented to the chiropractor with insidious neck pain and headaches, without
      neurological deficits. Radiographs revealed a widened atlantodental space
      (measuring 6 mm) indicating anterior atlantoaxial subluxation and potential
      sagittal atlantoaxial instability. Prompt detection and appropriate conservative
      management resulted in favourable long-term outcome at 13-months follow-up.
      Conservative management included education, mobilizations, soft tissue therapy,
      monitoring for neurological progression, and co-management with the family
      physician. The purpose of this case report is to heighten awareness of the
      clinical presentation of idiopathic anterior atlantoaxial subluxation without
      neurological deficits. Discussion will focus on the incidence, mechanism,
      clinical presentation, and conservative management of a complex case of anterior
      atlantoaxial subluxation. 

PMID- 24587501
TI  - Pilot study of the impact that bilateral sacroiliac joint manipulation using a
      drop table technique has on gait parameters in asymptomatic individuals with a
      leg length inequality.
AB  - PURPOSE: The purpose of this study was to pilot test our study procedures and
      estimate parameters for sample size calculations for a randomized controlled
      trial to determine if bilateral sacroiliac (SI) joint manipulation affects
      specific gait parameters in asymptomatic individuals with a leg length inequality
      (LLI). METHODS: Twenty-one asymptomatic chiropractic students engaged in a
      baseline 90-second walking kinematic analysis using infrared Vicon(r) cameras.
      Following this, participants underwent a functional LLI test. Upon examination
      participants were classified as: left short leg, right short leg, or no short
      leg. Half of the participants in each short leg group were then randomized to
      receive bilateral corrective SI joint chiropractic manipulative therapy (CMT).
      All participants then underwent another 90-second gait analysis. Pre- versus post
      intervention gait data were then analyzed within treatment groups by an
      individual who was blinded to participant group status. For the primary analysis,
      all p-values were corrected for multiple comparisons using the Bonferroni method.
      RESULTS: Within groups, no differences in measured gait parameters were
      statistically significant after correcting for multiple comparisons. CONCLUSIONS:
      The protocol of this study was acceptable to all subjects who were invited to
      participate. No participants refused randomization. Based on the data collected,
      we estimated that a larger main study would require 34 participants in each
      comparison group to detect a moderate effect size.

PMID- 24587502
TI  - Letters to the editor.

PMID- 24587503
TI  - Ethical question on food animal practitioner treating mange--a comment.

PMID- 24587504
TI  - Animal welfare....What is the veterinarian's role?

PMID- 24587505
TI  - An ethicist's commentary on compensation for emergency calls.

PMID- 24587506
TI  - Determination of the normal arthroscopic anatomy of the femoropatellar and
      cranial femorotibial joints of cattle.
AB  - The arthroscopic approach and anatomy of the bovine femoropatellar and
      femorotibial joints are described. A 4-mm diameter, 15-cm long arthroscope with a
      30 degrees  forward angle view was used. The structures viewed were recorded
      according to the position of the arthroscope within the joint. The femoropatellar
      joint was best accessed via a lateral approach, between the middle and lateral
      patellar ligaments. The axial portion of the medial femorotibial joint was viewed
      from a medial approach between the middle and medial patellar ligaments and the
      abaxial portion was viewed from a lateral approach between the middle and the
      lateral patellar ligaments. The axial portion of the lateral femorotibial joint
      was viewed from a lateral approach between the middle and the lateral patellar
      ligaments and the abaxial portion was viewed from a medial approach between the
      middle and medial patellar ligaments. The results of this study provide
      guidelines regarding the location of arthroscopic portals to evaluate precisely
      different areas of the stifle in cattle. 

PMID- 24587507
TI  - Detection of Leptospira spp. in wildlife reservoir hosts in Ontario through
      comparison of immunohistochemical and polymerase chain reaction genotyping
      methods.
AB  - A total of 460 kidney samples from wildlife (beavers, coyotes, deer, foxes,
      opossums, otters, raccoons, skunks) were obtained from road-kill and
      hunter/trapper donations in Ontario between January 2010 and November 2012. The
      objectives of the study were to detect Leptospira spp. by immunohistochemistry
      and polymerase chain reaction (PCR), to map presence of leptospires in wildlife
      relative to livestock and human populations, and to characterize positive samples
      by sequencing and comparison to leptospires known to affect domestic animals and
      humans. The proportion of samples that tested positive ranged from 0% to 42%,
      with the highest rates in skunks and raccoons. Leptospira spp. were present in
      kidneys of wildlife across Ontario, particularly in areas of high human density,
      and areas in which livestock populations are abundant. The PCR was too weak in
      most samples to permit genotyping and examination of the relationship between the
      leptospires found in this study and those affecting domestic animals and humans. 

PMID- 24587508
TI  - Complications associated with tibial plateau leveling osteotomy: a retrospective
      of 1519 procedures.
AB  - This retrospective study identified complications associated with tibial plateau
      leveling osteotomy (TPLO) and predisposing factors for these complications in a
      large population of dogs from a metropolitan area with cruciate ligament
      deficiency. There were 943 dogs that underwent unilateral TPLO and 288 with
      staged bilateral TPLO for a total of 1519 procedures. There were 47 cases with at
      least 1 major complication and 126 cases with at least 1 minor complication but
      no major complications. The total complication rate (major or minor) was 11.4%
      [95% confidence interval (CI) estimate: 9.8%, 13.2%]; the major complication rate
      was 3.1% (95% CI: 2.3%, 4.1%); and the minor complication rate was 8.3% (95% CI:
      7.0%, 9.8%). Factors associated with development of complications included being
      a German shepherd dog [odds ratio (OR): 3.2], tibial plateau angle > 30 degrees 
      (OR: 1.6), and heavier weights (for every 4.5 kg increase in body weight the OR
      increased by 1.10). Tibial plateau leveling osteotomy is a common treatment for
      dogs with cruciate ligament deficiency and has a low complication rate. 

PMID- 24587509
TI  - Comparison of 3 methods of onychectomy.
AB  - The frequency of claw regrowth, bony remnants, and complications in cats that
      underwent forelimb onychectomy using laser, scalpel, or guillotine techniques
      were evaluated. Eighty-seven client-owned cats were recruited from 27 veterinary
      clinics in the Canadian Atlantic provinces. At least 1 year after onychectomy the
      cats underwent a physical examination, gait analysis, and radiographic evaluation
      by 1 of 2 authors. There was no significant difference in the frequency of claw
      regrowth among the 3 methods (P = 0.283). Significantly more cats had bony
      remnants following guillotine onychectomy (P < 0.001). Bony remnants were
      significantly associated with claw regrowth (P = 0.001). Cats that underwent
      laser onychectomy had significantly less post-operative complications (P =
      0.023). The long-term outcome was not significantly different among the 3
      methods. We conclude that leaving remnants of the third phalanx in situ is
      associated with an increased frequency of claw regrowth. Laser onychectomy may be
      preferred to reduce the risk of post-operative complications, bony remnants, and
      claw regrowth. 

PMID- 24587510
TI  - Management and long-term outcome of partial glossectomy in 2 horses.
AB  - Records were reviewed for 2 horses with partial glossectomy, 1 traumatic and 1
      elective. According to long-term follow-up by telephone, both horses had
      recovered well, experiencing only temporary difficulty while eating, and went on
      to be ridden successfully using mouth bits. Partial glossectomy, therefore, had a
      favorable prognosis in 2 performance horses. 

PMID- 24587511
TI  - Infrared thermography to evaluate lameness in pregnant sows.
AB  - Early detection of lameness in sows is important to reduce losses and improve
      animal welfare. Mild-to-moderate lameness is difficult to diagnose in sows.
      Infrared thermography (IRT) was evaluated as a method of detecting signs of
      inflammation in the lower limbs as an aid in lameness detection. 

PMID- 24587512
TI  - Stewardship of antimicrobial drugs in animals in Canada: how are we doing?

PMID- 24587513
TI  - Provincial fees.

PMID- 24587514
TI  - Diagnostic ophthalmology.

PMID- 24587515
TI  - Guar gum: processing, properties and food applications-A Review.
AB  - Guar gum is a novel agrochemical processed from endosperm of cluster bean. It is
      largely used in the form of guar gum powder as an additive in food,
      pharmaceuticals, paper, textile, explosive, oil well drilling and cosmetics
      industry. Industrial applications of guar gum are possible because of its ability
      to form hydrogen bonding with water molecule. Thus, it is chiefly used as
      thickener and stabilizer. It is also beneficial in the control of many health
      problems like diabetes, bowel movements, heart disease and colon cancer. This
      article focuses on production, processing, composition, properties, food
      applications and health benefits of guar gum. 

PMID- 24587516
TI  - Starch accumulation, activities of key enzyme and gene expression in starch
      synthesis of wheat endosperm with different starch contents.
AB  - In order to investigate starch accumulation, and the enzymes activity changes and
      the expression levels of genes and their relationships among them at different
      developmental stages of wheat grain. We choose Annong9912 and E28 were used in
      the study. During starch accumulating rate and grain filling rate, and there were
      obvious genotype difference between Annong9912 and E28. Whether low or high
      starch content of starch content, the accumulation courses of amylopectin,
      amylose and total starch were well fitted to the logistic equation by relating
      starch contents against DAP. The simulation parameters revealed that the higher
      contents of amylopectin and amylose resulted from earlier initiating accumulation
      time and greater accumulation rate. And amylose, amylopectin and total starch
      accumulation rate of two wheat cultures were significantly and positively
      correlated with activities of SBE, SSS and GBSS, but amylose accumulation rate of
      E28 had no correlation with the activities of SBE. In addition, there were
      significant correlations among activities of SBE, SSS and GBSS in two wheat
      cultivars. We speculated that these enzymes proteins may have a coordinating
      action in starch biosynthesis within the amyloplast, operating as functional
      multiprotein complexes. And expression levels of enzyme genes demonstrated a
      single-peak curve, and 12-18 DAP reached their peaks and then began to drop, and
      all had high expression level in earlier stage of endosperm development, but in
      E28 were higher than in Annong9912. The GBSS-I transcripts on average were
      expressed over 60 times more than GBSS-II transcript in E28. SBE, SSS, DBE may
      control starch synthesis at the transcriptional level, and GBSS-I may control
      starch synthesis at the post transcriptional level. The expression level of DBE
      on average was lower than SS-1 and SBE-IIa genes, and similar to SS-III and SBE
      IIb genes, but higher than GBSS-I and GBSS-II genes. 

PMID- 24587517
TI  - Evaluation of some qualitative variations in frozen fillets of beluga (Huso huso)
      fed by different carbohydrate to lipid ratios.
AB  - In this study, juvenile beluga (Huso huso) was fed by the diets containing
      different carbohydrate to lipid ratios for 5 months. At the end of culture
      period, proximate compositions of the fish carcasses (moisture, protein, lipid,
      and ash) were measured. Then, qualitative changes in the fishes were evaluated
      during 6 months frozen storage (-20  degrees C) along with recording changes in
      their Total Volatile Bases Nitrogen (TVN), Thiobarbituric Acid (TBA), Free Fatty
      Acids (FFA), pH, and muscle texture profile analysis. The results of proximate
      analysis of the carcasses showed that moisture, protein, and ash of the carcasses
      increased significantly (p < 0.05) with higher carbohydrate to lipid ratio, but
      lipid content of the carcasses decreased significantly (p < 0.05). Also, during
      frozen storage, TVN, TBA, and FFA increased significantly in all the samples (p <
      0.05). Significant differences were detected in pH of the treatments (p < 0.05),
      but these changes didn't follow a regular pattern in all the treatments. The
      results of muscle texture profile analysis showed lower chewiness, hardness, and
      gumminess during the first 3 months of frozen storage; however, after 6 month,
      the values increased significantly compared to those in 3 months. Different
      characteristics of texture showed significant differences in the treatments
      during frozen storage (p < 0.05), although these changes didn't follow an
      identical pattern in all the treatments. It can be concluded that carbohydrate
      higher than 27% in diet has had adverse effect on quality of fillets during
      frozen storage. However, lipid levels used in the present study haven't had
      significant influence on quality of the fillets during the preservation. 

PMID- 24587518
TI  - Investigation of different parameters on acrylamide production in the fried beef
      burger using Taguchi experimental design.
AB  - Acrylamide is a carcinogenic compound which is produced as a result of thermal
      processing of food materials such as French fries, cereals and meat products. In
      this study the effects of four different parameters on the level of produced
      acrylamide in two types of beef burgers during the frying was investigated. Each
      parameter was used in three levels (temperature at 170, 190, and 210  degrees C;
      frying time at 5, 6, and 7 min and meat level at 30, 60, and 85%, and also three
      types of oil, corn, canola and sunflower). Taguchi's L9 design was applied to
      carry out the experiments. While temperature and meat level indicated more effect
      on the production of acrylamide in the studied samples, type of oil did not show
      any significant effects at all. Frying time (within the range studied here)
      showed minor contribution on the acrylamide level produced during the frying. 

PMID- 24587519
TI  - Antioxidative activity of protein hydrolysate produced by alcalase hydrolysis
      from shrimp waste (Penaeus monodon and Penaeus indicus).
AB  - Protein hydrolysates prepared by hydrolysis of shrimp waste (Penaeus monodon and
      Penaeus indicus) for 90 min. using Alcalase enzyme following pH-stat method.
      Antioxidative activities of SWPH were assessed determining FRAP, ABTS and DPPH
      radical scavenging activities, which increased linearly with increasing
      concentration of protein hydrolysate upto 5 mg/ml maintaining good correlation.
      SWPH showed high stability over wide ranges of pH (2-11) and temperature (up to
      100  degrees C for 150 min), in which the activity of more than 80% was retained.
      Protein hydrolysate solution with a concentration of 5 mg/ml significantly
      lowered TBA values of Croaker fish fillet and maintained yellowishness of skin
      colour compared to untreated control sample during 10 days of refrigerated
      storage at 4  degrees C. SWPH also restricted the increase of PV and FFA values
      in Croaker fish fillet within acceptable limit. 

PMID- 24587520
TI  - Pesticide residue analysis in parsley, lettuce and spinach by LC-MS/MS.
AB  - In this study, pesticide residues in parsley, lettuce and spinach (120 samples)
      were analyzed by the application of liquid chromatography-tandem mass
      spectrometry (LC-MS/MS). All samples of spinach, parsley or lettuce contained
      residues of three or more active substances. In parsley, carbendazim (100.0%),
      dichlorvos (100.0%), fenarimol (40.0%), pendimethalin (95.0%), in lettuce,
      diazinon (30.0%), dichlorvos (100.0%), pendimethalin (92.5%) phenthoate (12.5%),
      and in spinach, carbendazim (45.0%), cymoxanil (85.0%), dichlorvos (100.0%) and
      fenarimol (85.0%) were the significant active compounds. The maximum residue
      limits were exceeded in 28, 20 and 40 samples of parsley, lettuce and spinach,
      respectively. The results showed that there was a high occurrence of pesticide
      residues in parsley, lettuce and spinach samples from Hatay province, in which
      most of them were prohibited from use in Turkey for these vegetables. The
      contamination levels of these residues may be considered a serious public health
      problem according to the maximum residue limits (MRLs) of Turkey and the European
      Union (EU). 

PMID- 24587521
TI  - Kinetic characterization of Channa striatus muscle sarcoplasmic and myofibrillar
      protein hydrolysates.
AB  - This study was conducted to evaluate the kinetic characteristics of proteolytic
      activity of proteases on Channa striatus protein fractions. Degree of hydrolysis
      (DH), amino acid composition and kinetic parameters of sarcoplasmic and
      myofibrillar proteins were investigated when incubated with proteinase K and
      thermolysin, separately. After 30 min incubation with proteases, a decrease in DH
      of sarcoplasmic protein was observed whereas, hydrolysis of myofibrillar protein
      with proteases took 2 h with an increase in DH. The major amino acids were
      glutamic acid (16.6%) in thermolysin- myofibrillar hydrolysate followed by
      aspartic acid (11.1%) in sarcoplasmic protein fraction with no enzyme treatment
      and lysine (10%) in thermolysin-myofibrillar hydrolysate. The apparent Michaelis
      constant of proteinase K was lower than thermolysin for both sarcoplasmic and
      myofibrillar proteins. However, rate of turnover and enzyme efficiency suggested
      that sarcoplasmic and myofibrillar proteins are suitable substrates for
      proteinase K and thermolysin hydrolytic reaction, respectively. 

PMID- 24587522
TI  - Rapid determination of main constituents of packed juices by reverse phase-high
      performance liquid chromatography: an insight in to commercial fruit drinks.
AB  - The present work reports the compositional analysis of thirteen different packed
      fruit juices using high performance liquid chromatography (HPLC). Vitamin C,
      organic acids (citric and malic) and sugars (fructose, glucose and sucrose) were
      separated, analyzed and quantified using different reverse phase methods. A new
      rapid reverse phase HPLC method was developed for routine analysis of vitamin C
      in fruit juices. The precision results of the methods showed that the relative
      standard deviations of the repeatability and reproducibility were <0.05 and <0.1
      respectively. Correlation coefficient of the calibration models developed was
      found to be higher than 0.99 in each case. It has been found that the content of
      Vitamin C was less variable amongst different varieties involved in the study. It
      is also observed that in comparison to fresh juices, the packed juices contain
      lesser amounts of vitamin C. Citric acid was found as the major organic acids
      present in packed juices while maximum portion of sugars was of sucrose.
      Comparison of the amount of vitamin C, organic acids and sugars in same fruit
      juice of different commercial brands is also reported. 

PMID- 24587523
TI  - Effects of oxidative modification on thermal aggregation and gel properties of
      soy protein by malondialdehyde.
AB  - Malondialdehyde (MDA) was selected as a representative of lipid peroxidation
      products to investigate the effects of oxidative modification on thermal
      aggregation and gel properties of soy protein by lipid peroxidation products.
      Incubation of soy protein with increasing concentration of MDA resulted in
      gradual decrease of particle size and content of thermal aggregates during heat
      denaturation. Oxidative modification by MDA resulted in a decrease in water
      holding capacity, gel hardness, and gel strength of soy protein gel. An increase
      in coarseness and interstice of MDA modified protein gel network was accompanied
      by uneven distribution of interstice as MDA concentration increased. The results
      showed that degree of thermal aggregation of MDA-modified soy protein gradually
      decreased as MDA concentration increased, which contributed to a decrease in
      water holding capacity, gel hardness, and gel strength of MDA-modified soy
      protein gel. 

PMID- 24587524
TI  - Effect of processing on the microstructure of finger millet by X-ray diffraction
      and scanning electron microscopy.
AB  - Finger millet is one of the important minor cereals, and carbohydrates form its
      major chemical constituent. Recently, the millet is processed to prepare
      hydrothermally treated (HM), decorticated (DM), expanded (EM) and popped (PM)
      products. The present research aims to study the changes in the microstructure of
      carbohydrates using X-ray diffraction and scanning electron microscopy.
      Processing the millet brought in significant changes in the carbohydrates. The
      native millet exhibited A-type pattern of X-ray diffraction with major peaks at
      2theta values of 15.3, 17.86 and 23.15 degrees , whereas, all other products
      showed V-type pattern with single major peak at 2theta values ranging from 19.39
      to 19.81 degrees . The corresponding lattice spacing and the number of unit cells
      in a particular direction of reflection also reduced revealing that crystallinity
      of starch has been decreased depending upon the processing conditions. Scanning
      electron microscopic studies also revealed that the orderly pattern of starch
      granules changed into a coherent mass due to hydrothermal treatment, while high
      temperature short time treatment rendered a honey-comb like structure to the
      product. However, the total carbohydrates and non-starch polysaccharide contents
      almost remained the same in all the products except for DM and EM, but the
      individual carbohydrate components changed significantly depending on the type of
      processing. 

PMID- 24587525
TI  - Quality characteristics and stability of Moringa oleifera seed oil of Indian
      origin.
AB  - Cold pressed and hexane extracted moringa seed oils (CPMSO and HEMSO) were
      evaluated for their physico-chemical and stability characteristics. The iodine
      value, saponification value and unsaponifiable matter of CPMSO and HEMSO were
      found to be 67.8 and 68.5 g I2 / 100 g oil, 190.4 and 191.2 mg KOH / g oil and
      0.59 and 0.65%, respectively. The total tocopherols of CPMSO and HEMSO were found
      to be 95.5 and 90.2 mg/Kg. The fatty acid composition of CPMSO and HEMSO showed
      oleic acid as the major fatty acid (78-79%). The oxidative, thermal and frying
      stabilities of the CPMSO were compared with commercial raw and refined groundnut
      oil (GNO and RGNO). The CPMSO was of adequate thermal stability and better
      oxidative stability as it showed 79% lesser peroxide formation than GNO. The
      frying stability of CPMSO was better as it showed lower increase in free fatty
      acid (28%), peroxide value (10 meq O2/Kg) and color (25%) than RGNO (48%, 22 meq
      O2/kg and 52%, respectively) after frying. 

PMID- 24587526
TI  - Evaluation of quality characteristics of chicken meat emulsion/nuggets prepared
      by using different equipment.
AB  - Chicken meat emulsions prepared using food processor (FP), an indigenous meat
      cutter (MC) and bowl chopper (BC) were evaluated for physicochemical, texture and
      electron microscopic studies (SEM). Product yield, emulsion stability, hydration
      properties and gel strength (N) were significantly (P < 0.05) higher in BC. Total
      fluid release (TFR), water release (WR) and fat release (FR) was lowest in BC.
      Significantly (P < 0.05) higher lightness (L) in BC and redness (a) in FP
      emulsion were observed. Higher firmness, gumminess, chewiness and cohesiveness
      were observed in BC emulsion. SEM studies revealed a dense and compact protein
      matrix characteristic of heat induced protein gels. All micrographs showed
      structures that are compatible with fat globules, muscle fiber, meat protein
      matrix and heat induced gel/protein matrix. Sensory evaluation showed no
      significant difference between three treatments for colour, flavour, texture and
      acceptability scores. Thus, food processor and indigenously developed meat cutter
      found suitable for producing a stable chicken meat emulsion required for
      indigenous meat products. 

PMID- 24587527
TI  - Soy whey based medium for optimized phytase activity in Saccharomyces cerevisiae
      MTCC 5421 and alpha-D-galactosidase and antibacterial activities in Lactobacillus
      plantarum MTCC 5422 by response surface methodology.
AB  - Soy whey based growth medium for yeast enabled the native isolate of
      Saccharomyces cerevisiae MTCC 5421 to produce 198 U/ml of phytase activity
      against that of 135 U/ml in potato dextrose broth. In the same medium for lactic
      acid bacteria, the isolate of Lactobacillus plantarum MTCC 5422 was able to
      elaborate alpha-D-galactosidase activity of 10.6 U/ml in comparison to 6 U/ml in
      Lactobacillus MRS broth. Using this formulated medium, a central composite
      experimental design based on 5 variables of 3 factors namely incubation
      temperature, pH level and incubation period showed that S. cerevisiae could
      produce 200 U/ml of phytase in 36 h at 30  degrees C and pH 3.5. Similarly, L.
      plantarum in 33 h at 37  degrees C and pH 6.6 exhibited 14.2 U/ml of alpha-D
      galactosidase activity, whereas the antibacterial activity of 14.4 AU/ml against
      Bacillus cereus was evident in 42 h at 42  degrees C and pH 6.0. The phytase and
      antibacterial activity units visualized in response surface plots were more or
      less close to those obtained with the experimental design treatments. 

PMID- 24587528
TI  - Evaluation of finger millet incorporated noodles for nutritive value and glycemic
      index.
AB  - The present study was undertaken to develop finger millet incorporated noodles
      for diabetic patients. Finger millet variety VL-149 was taken. The finger millet
      flour and refined wheat flour (RWF) were evaluated for nutrient composition. The
      finger millet flour (FMF) was blended in various proportions (30 to 50%) in
      refined wheat flour and used for the preparation of noodles. Control consisted of
      RWF noodles. Sensory quality and nutrient composition of finger millet noodles
      was evaluated. The 30% finger millet incorporated noodles were selected best on
      the basis of sensory evaluation. Noodles in that proportion along with control
      were evaluated for glycemic response. Nutrient composition of noodles showed that
      50% finger millet incorporated noodles contained highest amount of crude fat
      (1.15%), total ash (1.40%), crude fiber (1.28%), carbohydrate (78.54%),
      physiological energy (351.36 kcal), insoluble dietary fiber (5.45%), soluble
      dietary fiber (3.71%), iron (5.58%) and calcium (88.39%), respectively. However,
      control RWF noodles contained highest amount of starch (63.02%), amylose (8.72%)
      and amylopectin (54.29%). The glycemic index (GI) of 30% finger millet
      incorporated noodles (best selected by sensory evaluation) was observed
      significantly lower (45.13) than control noodles (62.59). It was found that
      finger millet flour incorporated noodles were found nutritious and showed
      hypoglycemic effect. 

PMID- 24587529
TI  - Evaluation of wheat gluten hydrolysates as taste-active compounds with
      antioxidant activity.
AB  - Wheat gluten was subjected to enzymatic hydrolysis with various proteases
      (Alcalase, Flavourzyme, Protamex) and the taste-enhancing properties and
      antioxidant activities of the resulting wheat gluten hydrolysates (WGHs) were
      characterized. The contents of the hydrophobic amino acid of the WGHs were highly
      correlated with the degree of hydrolysis by Flavourzyme and Protamex, except
      Alcalase. The taste profiles of the Alcalase-treated WGHs showed decreased
      bitterness while umami and overall acceptability increased. On the other hand,
      the WGHs produced by Flavourzyme and Protamex showed increased bitterness with
      increasing hydrolysis duration. However, taste profiles, such as umami, kokumi,
      and overall acceptability of the WGHs by Flavourzyme and Protamex were unaffected
      by the degree of hydrolysis. The WGH treated by Alcalase for 24 h (A24h)
      exhibited taste-enhancing property and its antioxidant effects were concentration
      dependent. As a result, the A24h may be used as a multi-functional seasoning
      ingredient having potential antioxidant activity. 

PMID- 24587530
TI  - Effect of storage conditions of egg on rheological properties of liquid whole
      egg.
AB  - In the present work the effect of storage conditions of egg on rheological
      properties of Liquid Whole Egg (LWE) prepared from stored eggs were evaluated
      using a Brookfield. Newtonian model and Ostwald-of-Waele (Power Law) model were
      fitted to the rheological data obtained by experiments, both represented a good
      adjustment to the rheological data. The Newtonian model has shown an R(2)value
      between 0.984 and 0.993 (P < 0.05) and 0.991 and 0.995 (P < 0.05) for LWE samples
      prepared from eggs stored at room temperatures and refrigerated temperatures. The
      Ostwald-of-Waele (Power Law) resulted in the best adjustment, presenting an
      average R(2) values higher than 0.99 in all the cases and further statistical
      analysis showed that power law model was appropriate to explain the correct
      rheological behaviour of LWE prepared from stored eggs. All the LWE samples
      showed pseudoplastic and thixiotropic behaviour in the experimental conditions. 

PMID- 24587531
TI  - Physical characteristics and nutritional composition of some new soybean (Glycine
      max (L.) Merrill) genotypes.
AB  - Soybean is a major source of high quality protein and oil and soybean seed
      quality is often determined by seed nutritional and antinutritional parameters.
      The objective of this study was to investigate the physical characteristics and
      nutritional composition of some new soybean genotypes. Hundred seed weight and
      volume of soybean genotypes ranged from 8.7 to 11.1 g and 8.1 to 12.0 ml
      respectively, whereas, percent water absorption and percent volume expansion
      values ranged from 94.3 to 119.5% and 70.8 to 159.5% respectively. The genotypes
      contained % crude protein (39.4-44.4), oil (14.0-18.7), starch (4.3-6.7), total
      soluble sugars (5.6-7.9), reducing sugars (0.21-0.33) and sucrose (5.6-11.8). The
      free fatty acid and triglyceride content ranged from 31-71 mg 100 g(-1) oil and
      90.1-93.9 g 100 g(-1) oil respectively. The antinutritional components determined
      include: mg g(-1) TIA (41.5-85.0), phytate (2.3-5.6), total phenols (1.0-1.5),
      flavonols (0.20-0.34) and ortho-dihydroxy phenols (0.10-0.21). A significant
      variation for the 11S/7S ratio was observed among the 8 soybean genotypes and the
      values ranged from 0.70 ('SL 768' and 'SL 869') to 2.4 ('SL 794'). 

PMID- 24587532
TI  - Sensory characterization of doda burfi (Indian milk cake) using Principal
      Component Analysis.
AB  - Traditional sweetmeats of various countries hold a great and promising scope in
      their improvement and in order to tap the potential of the same, several
      companies and co-operative federations have started their organized production.
      Doda burfi, a heat desiccated and popular sweetmeat of northern India, is one of
      the regional specific, unfamiliarized products of India. The typical sweetmeat is
      characterized by caramelized and nutty flavour and granular texture. The purpose
      of this study was to determine the close relationship among various sensory
      attributes of the product collected from renowned manufacturers located in four
      different cities and to characterize an overall acceptable product. Individuals
      from academia participated in a round table discussion to generate descriptive
      terms related to colour and appearance, flavour and texture. Prior to sensory
      evaluation, sensory panel was trained and briefed about the terminology used to
      judge the product involving a descriptive intensity scale of 100 points for
      describing major sensory attributes. Results were analyzed using ANOVA and
      principal component analysis. Correlation table indicated a good degree of
      positive association between the attributes such as glossy appearance, dark
      colour, caramelized and nutty flavour and cohesive and chewy texture with the
      overall acceptability of the product. 

PMID- 24587533
TI  - Effect of different coagulants at varying strengths on the quality of paneer made
      from reconstituted milk.
AB  - A study was conducted to determine the effect of different types of acids viz.,
      citric acid, tartaric acid and malic acid each at 2, 3 and 5% concentrations on
      the quality of paneer made using reconstituted milk. The moisture, total solid
      recovery and yield and sensory scores for flavour, body and texture and overall
      acceptability of paneer decreased with the increasing strength of acid. However,
      these parameters for paneer made using coagulants at 2 and 3% levels were
      statistically comparable (P > 0.05). Fat and protein per cent increased with the
      increase in the concentration of the acid. No difference was observed in the
      levels of ash and fat on dry matter basis and pH and appearance scores at all the
      three concentrations of the coagulants. The type of coagulant also elicited
      variations in most of the constituents of paneer. The paneer samples made with
      citric acid and tartaric acid had significantly higher (P <= 0.05) values for
      fat, protein, ash, total solids recovery, fat on dry matter basis, body and
      texture and overall acceptability scores than paneer made with malic acid at all
      concentrations. No significant difference was seen in appearance and flavour
      scores among all the samples. In order to produce paneer with the most desirable
      characteristics from reconstituted milk, it is suggested citric acid and tartaric
      acid at 2% concentration can be utilized as coagulants. 

PMID- 24587534
TI  - Influence of defatted soy flour addition on the quality and stability of pretzel
      type product.
AB  - Effect of soya flour addition to 70% extraction bread wheat flour (PBW-343) at
      (0, 5, 10, 20 & 30%) was investigated for physico-chemical, dough handling and
      pretzel making properties. Results revealed that with increasing DSF addition,
      farinogram characteristics; water absorption, arrival time, dough development
      time and dough stability increased while mixing tolerance index and degree of
      softening decreased. Amylogram characteristics gelatinization temperature, peak
      viscosity, peak temperature and viscosity at 95  degrees C decreased with
      extended rate of DSF addition. Pretzels developed with different levels of DSF
      addition observed decrease in moisture, fat, non reducing sugars and starch where
      as ash, protein, reducing and total sugars increased compared to control.
      Calories calculated from proximate composition showed lower values than control
      due to high protein and low fat soy flour addition. Minerals increased
      significantly with increased levels of defatted soy flour addition. Organoleptic
      evaluation revealed that 5% level of soy flour blended pretzels were found best
      with respect to texture, colour and flavor on the basis of mean acceptability
      scores. Pretzels recorded shelf life of 90 days in laminated pouches irrespective
      of the level of DSF addition. 

PMID- 24587535
TI  - Effects of brine concentration on lipid oxidation and fatty acids profile of hot
      smoked tuna ( Thunnus albacares ) stored at refrigerated temperature.
AB  - This work evaluated the lipid oxidation and the changes in fatty acids in hot
      smoked tuna (Thunnus albacares) as a function of brine concentration. Fresh,
      commercially harvested tuna fish samples were purchased from a local supermarket.
      The fish were first immersed for 30 min in a brine solution at 5, 10, or 15%
      sodium chloride concentration and were then smoked at 50  degrees C for 3 h
      followed by 1 h at 60  degrees C and 3 h at 105  degrees C. The fish were then
      dried for 17 h, cooled and stored at 4  degrees C. Oxidative rancidity was
      measured by the peroxide value (PV), and thiobarbituric acid number (TBA) and
      fatty acids profile by GC-MS. Oxidative rancidity increased with storage time.
      The PV and TBARS values were more pronounced for samples immersed in 10% brine
      solution during the first 27 days of storage, whereas the lowest increase was
      observed for samples treated with 15% salt. Fatty acid concentration exhibited
      changes after smoking, and this was varied with salt concentration. The palmitic
      acid and stearic acid, the two main saturated fatty acids in tuna, increased
      after smoking at all brine concentration, whereas the contents of oleic acid,
      eicosapentaenoic acid and docosahexaenoic acid decreased. In conclusion, 15% NaCl
      treated tuna gave smoked product with less lipid oxidation and a fatty acid
      profile comparable to that for 5 and 10% NaCl-treated samples. 

PMID- 24587536
TI  - Storage stability and quality assessment of processed cereal brans.
AB  - Quality improvement of cereal brans, a health promoting ingredient for functional
      foods is the emerging research concept due to their low shelf stability and
      presence of non-nutrient components. A study was conducted to evaluate the
      storage quality of processed milling industry byproducts so that these can be
      potentially utilized as a dietary fibre source. Different cereal brans (wheat,
      rice, barley and oat) were processed by dry, wet, microwave heating, extrusion
      cooking and chemical methods at variable conditions. Processed brans were stored
      in high density polyethylene (HDPE) pouches at ambient and refrigeration
      temperature. Quality assessments (moisture, free fatty acids, water activity and
      physical quality) of brans were done up to six months, at one month intervals.
      Free fatty acid content, moisture and water activity of the cereal brans remained
      stable during the entire storage period. Among treatments, extrusion processing
      is the most effective for stability. Processing treatments and storage
      temperature have the positive effect on extending the shelf life of all cereal
      brans. Therefore, processed cereal brans can be used as a dietary fortificant for
      the development of value added food products. 

PMID- 24587537
TI  - Evaluation of the content and bioaccessibility of iron, zinc, calcium and
      magnesium from groats, rice, leguminous grains and nuts.
AB  - The objective of this study was to determine the content and the bioaccessibility
      of minerals (Fe, Zn, Ca and Mg) in commonly consumed food products, such as
      cereal groats, rice, leguminous grains and nuts purchased from the local market.
      The contents of Fe, Zn, Ca and Mg in foods were assayed after dry ashing of
      samples, while the bioaccessibility of these minerals after enzymatic in vitro
      digestion, was determined by flame atomic absorption spectrometry. A relatively
      high content of Fe was found in cashew nuts and green lentils, while cashew nuts
      and buckwheat groats had the highest concentration of Zn. It was found that the
      highest amount of macro-elements was generally in nuts, in particular: brazil
      nuts (Ca and Mg), cashews (Mg) and hazelnuts (Ca and Mg). Concerning the mineral
      bioaccessibility, the highest values for Fe were obtained in cashew nuts and
      green lentils (2.8 and 1.7 mg/100 g), for Zn in green lentils (2.1 mg/100 g), for
      Ca in brazil nuts and shelled pea (32.6 and 29.1 mg/100 g), while for Mg in
      shelled peas and green lentils (43.4 and 33.9 mg/100 g). Generally, the best
      sources of bioaccessible minerals seem to be leguminous grains and nuts. 

PMID- 24587538
TI  - Development and quality evaluation of quick cooking dhal-A convenience product.
AB  - Owing to rapid urbanization and more women joining the workforce, use of ready-to
      eat and ready-to-use convenience foods is gaining increasing popularity. Women
      require dhal that cooks fast and increases in volume when cooked. In an attempt
      to prepare quick cooking dhal from pigeon pea, variety UPAS 120 was milled, pre
      treated with sodium chloride solution (1%), flaked and dried. The quick cooking
      dhal was packed in three packaging materials, namely, high molecular weight high
      density polyethylene (HMHDPE), high density polyethylene (HDPE) and laminated
      pouches. The quality evaluation of the prepared flakes with respect to the
      cooking quality attributes, changes in proximate composition, free fatty acid
      (FFA) and peroxide value (PV) were carried out during storage at ambient
      temperature (8-36 degrees C) at regular intervals for a period of 10 months.
      During storage, quick cooking dhal packed in laminated pouches performed better
      than samples stored in other pouches with respect to the changes in the overall
      quality and acceptability of the product. 

PMID- 24587539
TI  - Preparation of cold water-soluble potato starch and its characterization.
AB  - Alcoholic-alkaline treatment of starch results in granular cold water-soluble
      starch. The nature of structural alterations occurred in starch due to the
      treatment is however relatively vague. Potato starch was treated at various
      alcoholic-alkali conditions and subjected to light microscopy, Fourier transform
      infrared (FTIR) spectroscopy and X-ray diffractometry. Alcoholic-alkaline
      treatment increased the solubility of starch in a temperature-dependant manner.
      The treated starch suspension was also more turbid than that of native
      counterpart at all concentrations, due probably to either the presence of higher
      number of water-soluble granules or leaching of amylose during alkalization.
      Alcoholic-alkali treating of starch did not disintegrate the granular assembly;
      albeit, decreased the crystalinity. Both native and treated starches showed the B
      type pattern in X-ray diffractometry. FTIR spectroscopy revealed that
      characteristic peaks of hydroxyl groups were of low transmittance in spectrum of
      treated starch compared with that of native counterpart implying in participation
      of hydroxyl groups in interactions with modifying agents. 

PMID- 24587540
TI  - Application of osmometry in quality analysis of milk.
AB  - The aim of this study was to evaluate osmometry as a tool in quality analysis of
      milk. The osmolality of raw milk, sterilized milk, skimmed UHT (ultra-high
      temperature-treated) milk, pasteurized milk, standardized UHT milk and fermented
      milk (Lactococcus lactis culture) was determined by freezing point osmometry. The
      relationship between osmolality and pH of fermented milk was further investigated
      during spontaneous fermentation of UHT milk at 37  degrees C for 48 h. Average
      osmolality values (mean +/- SD) were raw milk-290.2 +/- 7.98, sterilized milk
      290.2 +/- 5.84, skimmed UHT milk-290.8 +/- 3.31, pasteurized milk-283.6 +/- 2.28,
      standardized UHT milk-281 +/- 4.59 and fermented milk-466.0 +/- 17.30 mOsmoles
      kg(-1). For fresh milk samples, 88 % showed normal osmolality, 8 % were hypo
      osmotic and 4 % hyper-osmotic. Fermentation studies revealed a high negative
      correlation between osmolality and pH, with a correlation coefficient of -97.49
      %. Hypo-osmotic milk shows mixing of milk with water along the production chain.
      Hyper-osmotic milk indicates fermentation of milk at high ambient temperatures or
      with prolonged storage. It may also reveal adulteration of fresh milk with a
      soluble substance. Osmolality was highest for fermented milk owing to production
      of lactic acid during fermentation. This was confirmed by the high negative
      correlation between osmolality and pH of milk in fermentation studies. Hence the
      osmolality of fermented milks may be used as an index of the extent of
      fermentation. 

PMID- 24587541
TI  - Coral architecture affects the habitat choice and form of associated gobiid
      fishes.
AB  - Gobiid fishes of the genus Gobiodon live in strong association with certain reef
      building corals that vary considerably in size and architecture. These fishes
      hence are excellent model systems for studying evolutionary adaption to specific
      microhabitats. Using a sample of Gobiodon histrio and G. rivulatus and their most
      important host corals (Acropora digitifera and A. gemmifera) from the northern
      Red Sea, we assess (1) how corals that are occupied by gobies differ in their
      architecture from colonies that are not occupied and (2) how fish body shape is
      associated with the architecture of their host coral. Fish body shape was
      assessed by geometric morphometric techniques. Coral measurements included colony
      size, branch length (BL), and interbranch as well as branch tip distance of
      adjacent branches, for which we applied a new and non-destructive measurement
      technique based on casts of two-component epoxy resin. The most important factor
      influencing the occupation of corals was a BL of more than 5 cm. The distance
      between coral branches was clearly related to the width of the fishes and hence
      constrained overall fish size. G. histrio and G.rivulatus differ in adult body
      shape as well in their allometric development of lateral body compression,
      resulting in different maximum body sizes attainable in the restricted
      interbranch space of corals. The strong dependence of coral-associated fishes on
      large coral colonies with specific architectures increases the extinction risk of
      fishes within deteriorating coral reefs.

PMID- 24587542
TI  - A message from the editor.

PMID- 24587543
TI  - Surgeon general's perspectives.

PMID- 24587545
TI  - On the hard and soft sciences in public health.

PMID- 24587544
TI  - Recommendations from the National Vaccine Advisory committee: standards for adult
      immunization practice.

PMID- 24587546
TI  - Faith-based partnerships for population health: challenges, initiatives, and
      prospects.

PMID- 24587547
TI  - Infectious disease surveillance in the 21st century: an integrated web-based
      surveillance and case management system.
AB  - The Massachusetts Virtual Epidemiologic Network (MAVEN) was deployed in 2006 by
      the Massachusetts Department of Public Health, Bureau of Infectious Disease to
      serve as an integrated, Web-based disease surveillance and case management
      system. MAVEN replaced program-specific, siloed databases, which were
      inaccessible to local public health and unable to integrate electronic reporting.
      Disease events are automatically created without human intervention when a case
      or laboratory report is received and triaged in real time to state and local
      public health personnel. Events move through workflows for initial notification,
      case investigation, and case management. Initial development was completed within
      12 months and recent state regulations mandate the use of MAVEN by all 351
      jurisdictions. More than 300 local boards of health are using MAVEN, there are
      approximately one million events, and 70 laboratories report electronically.
      MAVEN has demonstrated responsiveness and flexibility to emerging diseases while
      also streamlining routine surveillance processes and improving timeliness of
      notifications and data completeness, although the long-term resource requirements
      are significant. 

PMID- 24587548
TI  - Prescription drug monitoring and dispensing of prescription opioids.
AB  - OBJECTIVE: In the United States, per-capita opioid dispensing has increased
      concurrently with analgesic-related mortality and morbidity since the 1990s. To
      deter diversion and abuse of controlled substances, most states have implemented
      electronic prescription drug monitoring programs (PDMPs). We evaluated the impact
      of state PDMPs on opioid dispensing. METHODS: We acquired data on opioids
      dispensed in a given quarter of the year for each state and the District of
      Columbia from 1999 to 2008 from the Automation of Reports and Consolidated Orders
      System and converted them to morphine milligram equivalents (MMEs). We used
      multivariable linear regression modeling with generalized estimating equations to
      assess the effect of state PDMPs on per-capita dispensing of MMEs. RESULTS: The
      annual MMEs dispensed per capita increased progressively until 2007 before
      stabilizing. Adjusting for temporal trends and demographic characteristics,
      implementation of state PDMPs was associated with a 3% decrease in MMEs dispensed
      per capita (p=0.68). The impact of PDMPs on MMEs dispensed per capita varied
      markedly by state, from a 66% decrease in Colorado to a 61% increase in
      Connecticut. CONCLUSIONS: Implementation of state PDMPs up to 2008 did not show a
      significant impact on per-capita opioids dispensed. To control the diversion and
      abuse of prescription drugs, state PDMPs may need to improve their usability,
      implement requirements for committee oversight of the PDMP, and increase data
      sharing with neighboring states.

PMID- 24587549
TI  - Assessment of state- and territorial-level preparedness capacity for serving deaf
      and hard-of-hearing populations in disasters.
AB  - OBJECTIVES: Substantial evidence exists that emergency preparedness and response
      efforts are not effectively reaching populations with functional and access
      needs, especially barriers related to literacy, language, culture, or
      disabilities. More than 36 million Americans are Deaf or hard of hearing
      (Deaf/HH). These groups experienced higher risks of injury, death, and property
      loss in recent disasters than the general public. We conducted a participatory
      research study to examine national recommendations on preparedness communication
      for the Deaf/HH. METHODS: We assessed whether previous recommendations regarding
      the Deaf/HH have been incorporated into state- and territorial-level emergency
      operations plans (EOPs), interviewed state- and territorial-level preparedness
      directors about capacity to serve the Deaf/HH, and proposed strategies to benefit
      Deaf/HH populations during emergencies. We analyzed 55 EOPs and 50 key informant
      (KI) interviews with state directors. RESULTS: Fifty-five percent of EOPs
      mentioned vulnerable populations; however, only 31% specifically mentioned
      Deaf/HH populations in their plan. Study findings indicated significant
      relationships among the following factors: a state-level KI's familiarity with
      communication issues for the Deaf/HH, making relay calls (i.e., calls to services
      to relay communication between Deaf and hearing people), and whether the KI's
      department provides trainings about serving Deaf/HH populations in emergencies.
      We found significant associations between a state's percentage of Deaf/HH
      individuals and a KI's familiarity with Deaf/HH communication issues and
      provision by government of any disability services to Deaf/HH populations in
      emergencies. Further, we found significant relationships between KIs attending
      training on serving the Deaf/HH and familiarity with Deaf/HH communication
      issues, including how to make relay calls. CONCLUSION: This study provides new
      knowledge that can help emergency agencies improve their preparedness training,
      planning, and capacity to serve Deaf/HH populations in emergencies.

PMID- 24587550
TI  - Rates of substance use of American Indian students in 8th, 10th, and 12th grades
      living on or near reservations: update, 2009-2012.
AB  - OBJECTIVES: Understanding the similarities and differences between substance use
      rates for American Indian (AI) young people and young people nationally can
      better inform prevention and treatment efforts. We compared substance use rates
      for a large sample of AI students living on or near reservations for the years
      2009-2012 with national prevalence rates from Monitoring the Future (MTF).
      METHODS: We identified and sampled schools on or near AI reservations by region;
      1,399 students in sampled schools were administered the American Drug and Alcohol
      Survey. We computed lifetime, annual, and last-month prevalence measures by grade
      and compared them with MTF results for the same time period. RESULTS: Prevalence
      rates for AI students were significantly higher than national rates for nearly
      all substances, especially for 8th graders. Rates of marijuana use were very
      high, with lifetime use higher than 50% for all grade groups. Other findings of
      interest included higher binge drinking rates and OxyContin((r)) use for AI
      students. CONCLUSIONS: The results from this study demonstrate that adolescent
      substance use is still a major problem among reservation-based AI adolescent
      students, especially 8th graders, where prevalence rates were sometimes
      dramatically higher than MTF rates. Given the high rates of substance use-related
      problems on reservations, such as academic failure, delinquency, violent criminal
      behavior, suicidality, and alcohol-related mortality, the costs to members of
      this population and to society will continue to be much too high until a
      comprehensive understanding of the root causes of substance use are established.

PMID- 24587551
TI  - High risk for HIV following syphilis diagnosis among men in Florida, 2000-2011.
AB  - OBJECTIVE: Multiple interventions have been shown to reduce the risk of HIV
      acquisition, including preexposure prophylaxis with antiretroviral medications,
      but high costs require targeting interventions to people at the highest risk. We
      identified the risk of HIV following a syphilis diagnosis for men in Florida.
      METHODS: We analyzed surveillance records of 13- to 59-year-old men in Florida
      who were reported as having syphilis from January 1, 2000, to December 31, 2009.
      We excluded men who had HIV infection reported before their syphilis diagnosis
      (and within 60 days after), then searched the database to see if the remaining
      men were reported as having HIV infection by December 31, 2011. RESULTS: Of the
      9,512 men with syphilis we followed, 1,323 were subsequently diagnosed as having
      HIV infection 60-3,753 days after their syphilis diagnosis. The risk of a
      subsequent diagnosis of HIV infection was 3.6% in the first year after syphilis
      was diagnosed and reached 17.5% 10 years after a syphilis diagnosis. The risk of
      HIV was higher for non-Hispanic white men (3.4% per year) than for non-Hispanic
      black men (1.8% per year). The likelihood of developing HIV was slightly lower
      for men diagnosed with syphilis in 2000 and 2001 compared with subsequent years.
      Of men diagnosed with syphilis in 2003, 21.5% were reported as having a new HIV
      diagnosis by December 31, 2011. CONCLUSION: Men who acquire syphilis are at very
      high risk of HIV infection.

PMID- 24587552
TI  - Timely HIV diagnosis and HIV/TB comanagement among California patients in 2008.
AB  - OBJECTIVE: National guidelines highlight the roles of early HIV diagnosis and
      effective comanagement for HIV and tuberculosis (TB) to prevent mortality and
      morbidity from HIV-related TB. We assessed HIV diagnosis timing and HIV/TB
      comanagement for California HIV/TB patients. METHODS: We reviewed and analyzed
      public health charts for California HIV/TB patients reported during 2008. HIV
      diagnoses fewer than three months before TB diagnosis were considered new HIV
      diagnoses. We determined the proportion of patients with new HIV diagnoses, risk
      factors for new HIV diagnoses, and proportion of patients receiving recommended
      CD4 cell count measurements, supervised TB therapy, and antiretroviral therapy
      (ART). RESULTS: Of 130 HIV/TB patients, 51% had new HIV diagnoses. Foreign-born
      patients were more likely than U.S.-born patients to have new HIV diagnoses.
      Supervised TB therapy and CD4 cell count measurements followed national
      recommendations for 91% and 74% of patients, respectively. At least 73% of
      patients started ART before completing TB therapy. Compared with patients who had
      previous HIV diagnoses, patients with new HIV diagnoses started ART later and had
      lower CD4 cell counts and higher viral loads at TB diagnosis. CONCLUSIONS:
      Although most HIV/TB patients received the recommended treatment, half had new
      HIV diagnoses. Compared with patients who had previous HIV diagnoses, patients
      with new HIV diagnoses had greater immunosuppression at TB diagnosis. A new
      diagnosis indicates that HIV could have been diagnosed earlier and ART or
      treatment for latent TB infection could have been initiated to prevent TB
      development.

PMID- 24587553
TI  - Hospitalization rates of people living with HIV in the United States, 2009.
AB  - OBJECTIVES: We determined hospitalization rates and disparities among people with
      HIV, which may have been underestimated in previous studies, as only those in
      medical care were included. METHODS: We estimated the hospitalization rate of
      people with diagnosed HIV infection in the U.S. in 2009 using two nationally
      representative datasets. We took the number of hospitalizations from the
      Nationwide Inpatient Sample and searched each discharge for International
      Classification of Diseases, Ninth Revision codes for HIV infection and
      opportunistic infections (OIs). We divided the number of hospitalizations by the
      number of prevalent diagnosed HIV cases estimated by CDC to produce
      hospitalization rates, and then compared those rates using Z-tests. RESULTS: The
      estimated nationwide hospitalization rate was 26.6 per 100 population. Women had
      a 51% higher rate than men (35.5 vs. 23.5 per 100 population, p=0.002). Black
      people (31.2 per 100 population, p=0.01) had a 42% higher rate, and Hispanic
      people (18.2 per 100 population, p=0.23) had an 18% lower rate than white people
      (22.1 per 100 population) of hospitalization for any illness. Of hospitalizations
      with an OI, females with HIV had a 50% higher rate than males with HIV (5.0 vs.
      3.4 per 100 population, p=0.003). Black people with HIV (4.7 per 100 population,
      p<0.001) had a 72% higher rate and Hispanic people with HIV (2.9 per 100
      population, p=0.78) had a similar rate of hospitalization with an OI compared
      with white people with HIV (2.7 per 100 population). CONCLUSIONS: Hospitalization
      rates among people living with HIV in the U.S. are higher than have been
      previously estimated. Substantial gender and racial/ethnic disparities in
      hospitalization rates exist, suggesting that the benefits of antiretroviral
      therapy have not been realized across all groups equally.

PMID- 24587554
TI  - Hepatitis C seroprevalence among prison inmates since 2001: still high but
      declining.
AB  - OBJECTIVES: Although the hepatitis C epidemic in the United States
      disproportionately affects correctional populations, the last national estimates
      of seroprevalence and disease burden among these populations are more than a
      decade old. We investigated routine hepatitis C surveillance conducted in state
      prison systems and updated previous estimates. METHODS: We surveyed all U.S.
      state correctional departments to determine which state prison systems had
      performed routine hepatitis C screening since 2001. Using seroprevalence data for
      these prison systems, we estimated the national hepatitis C seroprevalence among
      prisoners in 2006 and the share of the epidemic borne by correctional
      populations. RESULTS: Of at least 12 states performing routine testing from 2001
      to 2012, seroprevalences of hepatitis C ranged from 9.6% to 41.1%. All but one
      state with multiple measurements demonstrated declining seroprevalence. We
      estimated the national state prisoner seroprevalence at 17.4% in 2006. Based on
      the estimated total U.S. correctional population size, we projected that
      1,857,629 people with hepatitis C antibody were incarcerated that year. We
      estimated that correctional populations represented 28.5%-32.8% of the total U.S.
      hepatitis C cases in 2006, down from 39% in 2003. CONCLUSIONS: Our results
      provide an important updated estimate of hepatitis C seroprevalence and suggest
      that correctional populations bear a declining but still sizable share of the
      epidemic. Correctional facilities remain important sites for hepatitis C case
      finding and therapy implementation. These results may also assist future studies
      in projecting the societal costs and benefits of providing new treatment options
      in prison systems.

PMID- 24587558
TI  - Incorporating global health competencies into the public health curriculum.

PMID- 24587561
TI  - Characterization of oscillatory instability in lid driven cavity flows using
      lattice Boltzmann method.
AB  - In the present work, lattice Boltzmann method (LBM) is applied for simulating
      flow in a three-dimensional lid driven cubic and deep cavities. The developed
      code is first validated by simulating flow in a cubic lid driven cavity at 1000
      and 12000 Reynolds numbers following which we study the effect of cavity depth on
      the steady-oscillatory transition Reynolds number in cavities with depth aspect
      ratio equal to 1, 2 and 3. Turbulence modeling is performed through large eddy
      simulation (LES) using the classical Smagorinsky sub-grid scale model to arrive
      at an optimum mesh size for all the simulations. The simulation results indicate
      that the first Hopf bifurcation Reynolds number correlates negatively with the
      cavity depth which is consistent with the observations from two-dimensional deep
      cavity flow data available in the literature. Cubic cavity displays a steady flow
      field up to a Reynolds number of 2100, a delayed anti-symmetry breaking
      oscillatory field at a Reynolds number of 2300, which further gets restored to a
      symmetry preserving oscillatory flow field at 2350. Deep cavities on the other
      hand only attain an anti-symmetry breaking flow field from a steady flow field
      upon increase of the Reynolds number in the range explored. As the present work
      involved performing a set of time-dependent calculations for several Reynolds
      numbers and cavity depths, the parallel performance of the code is evaluated a
      priori by running the code on up to 4096 cores. The computational time required
      for these runs shows a close to linear speed up over a wide range of processor
      counts depending on the problem size, which establishes the feasibility of
      performing a thorough search process such as the one presently undertaken.

PMID- 24587559
TI  - Demographic disparities in the tobacco retail environment in Boston: a citywide
      spatial analysis.

PMID- 24587562
TI  - Use of Historical Pump-and-Treat Data to Enhance Site Characterization and
      Remediation Performance Assessment.
AB  - Groundwater withdrawal and contaminant concentration data are routinely collected
      for pump-and-treat operations conducted at hazardous waste sites. These data sets
      can be mined to produce a wealth of information to support enhanced site
      characterization, optimization of remedial system operations, and improved
      decision making regarding long-term site management and closure. Methods that may
      be used to analyze and interpret pump-and-treat data to produce such assessments
      are presented, along with a brief illustration of their application to a site.
      The results presented herein illustrate that comprehensive analysis of pump-and
      treat data is a powerful, cost-effective method for providing higher-resolution,
      value-added characterization of contaminated sites.

PMID- 24587563
TI  - Tradeoffs between global warming and day length on the start of the carbon uptake
      period in seasonally cold ecosystems.
AB  - It is well established that warming leads to longer growing seasons in seasonally
      cold ecosystems. Whether this goes along with an increase in the net ecosystem
      carbon dioxide (CO2) uptake is much more controversial. We studied the effects of
      warming on the start of the carbon uptake period (CUP) of three mountain
      grasslands situated along an elevational gradient in the Alps. To this end we
      used a simple empirical model of the net ecosystem CO2 exchange, calibrated and
      forced with multi-year empirical data from each site. We show that reductions in
      the quantity and duration of daylight associated with earlier snowmelts were
      responsible for diminishing returns, in terms of carbon gain, from longer growing
      seasons caused by reductions in daytime photosynthetic uptake and increases in
      nighttime losses of CO2. This effect was less pronounced at high, compared to
      low, elevations, where the start of the CUP occurred closer to the summer
      solstice when changes in day length and incident radiation are minimal.

PMID- 24587564
TI  - Rapid eye movement sleep behavioral events: a new marker for neurodegeneration in
      early Parkinson disease?
AB  - OBJECTIVE: To analyze potential markers in sleep for early recognition of
      neurodegenerative disease in newly diagnosed, unmedicated patients with Parkinson
      disease (PD) compared to controls. METHODS: Videopolysomnography (vPSG) was
      available in 158 newly diagnosed, unmedicated patients with PD and 110 age-, sex
      , and education-matched healthy controls (HC). Rapid eye movement (REM) sleep was
      analyzed for REM without atonia (RWA) and studied by review of time-synchronized
      video. Motor behaviors and/or vocalizations in REM sleep with a purposeful
      component other than comfort moves were identified as REM sleep behavioral events
      (RBE). Two or more events had to be present to be classified as "RBE positive."
      RBE subjects included rapid eye movement sleep behavior disorder (RBD) and non
      RBD subjects based on the presence or absence of RWA > 18.2%. RESULTS: RBE were
      detected in 81 of 158 patients with de novo PD (51%) and 17 of 110 HC (15%) (P <
      0.001). RBD was identified in 40/81 RBE-positive patients with PD (25% of all PD
      patients) and 2 of 17 RBE-positive HC (2% of all controls). RBE-positive patients
      showed no specific motor or neuropsychological features compared to RBE-negative
      patients. Patients with PD and HC with RBE had more REM sleep (P = 0.002) and a
      higher periodic leg movements in sleep index (P = 0.022) compared to subjects
      without RBE. CONCLUSION: This first description of REM sleep behavioral events
      (RBE) shows it occurs more frequently in patients with de novo Parkinson disease
      (PD) than in healthy controls and may be an early sign of neurodegeneration and
      precede rapid eye movement sleep behavior disorder (RBD). There is no specific
      phenotype of PD associated with newly defined RBE or RBD at this early stage.

PMID- 24587565
TI  - Increased mortality in narcolepsy.
AB  - OBJECTIVE: To evaluate the mortality rate in patients with narcolepsy. DESIGN:
      Data were derived from a large database representative of the US population,
      which contains anonymized patient-linked longitudinal claims for 173 million
      individuals. SETTING: Symphony Health Solutions (SHS) Source Lx, an anonymized
      longitudinal patient dataset. PATIENTS/PARTICIPANTS: All records of patients
      registered in the SHS database between 2008 and 2010. INTERVENTIONS: None.
      MEASUREMENTS AND RESULTS: Identification of patients with narcolepsy was based on
      >= 1 medical claim with the diagnosis of narcolepsy (ICD-9 347.xx) from 2002 to
      2012. Dates of death were acquired from the Social Security Administration via a
      third party; the third party information was encrypted in the same manner as the
      claims data such that anonymity is ensured prior to receipt by SHS. Annual all
      cause mortality rates for 2008, 2009, and 2010 were calculated retrospectively
      for patients with narcolepsy and patients without narcolepsy in the database, and
      standardized mortality ratios (SMR) were calculated. Mortality rates were also
      compared with the general US population (Centers for Disease Control data). SMRs
      of the narcolepsy population were consistent over the 3-year period and showed an
      approximate 1.5-fold excess mortality relative to those without narcolepsy. The
      narcolepsy population had consistently higher mortality rates relative to those
      without narcolepsy across all age groups, stratified by age decile, from 25-34
      years to 75+ years of age. The SMR for females with narcolepsy was lower than for
      males with narcolepsy. CONCLUSIONS: Narcolepsy was associated with approximately
      1.5-fold excess mortality relative to those without narcolepsy. While the cause
      of this increased mortality is unknown, these findings warrant further
      investigation.

PMID- 24587566
TI  - Associations between subjective sleep quality and brain volume in Gulf War
      veterans.
AB  - STUDY OBJECTIVES: To investigate whether subjective sleep quality is associated
      with brain volume independent of comorbid psychiatric conditions. DESIGN: Cross
      sectional. SETTING: Department of Veterans Affairs (VA) Medical Center.
      PARTICIPANTS: One hundred forty-four Gulf War Veterans (mean age 45 years; range:
      31-70 years; 14% female). INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Total
      cortical, lobar gray matter, and hippocampal volumes were quantified from 1.5
      Tesla magnetic resonance images using Freesurfer version 4.5. Subjective sleep
      quality was assessed with the Pittsburgh Sleep Quality Index (PSQI). Multiple
      linear regressions were used to determine the association of sleep quality with
      total and regional brain volumes. The global PSQI score was positively correlated
      with lifetime and current posttraumatic stress disorder (PTSD) and current
      depressive symptoms (P < 0.001) and was higher in veterans with Gulf War Illness,
      trauma exposure, and those using psychotropic medication (P <= 0.03). After
      adjusting for these comorbid variables, age, intracranial volume, and multiple
      comparisons, global PSQI was inversely associated with total cortical and frontal
      gray matter volume (adjusted P <= 0.03). Within the frontal lobe, total PSQI was
      inversely associated with the superior and middle frontal, orbitofrontal,
      anterior cingulate, and frontal pole volumes (adjusted P <= 0.02). Examination of
      the 3-factor structure of the PSQI revealed that the associations were driven by
      perceived sleep quality. CONCLUSIONS: Poorer subjective sleep quality was
      associated with reduced total cortical and regional frontal lobe volumes
      independent of comorbid psychiatric conditions. Future work will be needed to
      examine if effective treatment of disturbed sleep leads to improved structural
      and functional integrity of the frontal lobes.

PMID- 24587567
TI  - Cytokine polymorphisms are associated with poor sleep maintenance in adults
      living with human immunodeficiency virus/acquired immunodeficiency syndrome.
AB  - STUDY OBJECTIVES: Cytokine activity and polymorphisms have been associated with
      sleep outcomes in prior animal and human research. The purpose of this study was
      to determine whether circulating plasma cytokines and cytokine polymorphisms are
      associated with the poor sleep maintenance commonly experienced by adults living
      with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS).
      DESIGN: Cross-sectional descriptive study. SETTING: HIV clinics and community
      sites in the San Francisco Bay area. PARTICIPANTS: A convenience sample of 289
      adults (193 men, 73 women, and 23 transgender) living with HIV/AIDS.
      INTERVENTIONS: None. MEASUREMENTS AND RESULTS: A wrist actigraph was worn for 72
      h to estimate the percentage of wake after sleep onset (WASO%) and total sleep
      time (TST), plasma cytokines were analyzed, and genotyping was conducted for 15
      candidate genes involved in cytokine signaling: interferon-gamma (IFNG), IFNG
      receptor 1 (IFNGR1), interleukins (IL1B, IL1R2, IL1R2, IL2, IL4, IL6, IL8, IL10,
      IL13, IL17A), nuclear factor of kappa light polypeptide gene enhancer in B cells
      (NFKB1 and NFKB2), and tumor necrosis factor-alpha (TNFA). Controlling for
      demographic variables such as race and sex, and clinical variables such as CD4+
      count and medications, higher WASO% was associated with single nucleotide
      polymorphisms (SNPs) of IL1R2 rs11674595 and TNFA rs1041981 and less WASO% was
      associated with IL2 rs2069776. IL1R2 rs11674595 and TNFA rs1041981 were also
      associated with short sleep duration. CONCLUSIONS: This study strengthens the
      evidence for an association between inflammation and sleep maintenance problems.
      In this chronic illness population, cytokine polymorphisms associated with wake
      after sleep onset provide direction for intervention research aimed at comparing
      anti-inflammatory mechanisms with hypnotic agents for improving sleep maintenance
      and total sleep time.

PMID- 24587568
TI  - Total sleep deprivation alters endothelial function in rats: a nonsympathetic
      mechanism.
AB  - STUDY OBJECTIVES: Sleep loss is suspected to induce endothelial dysfunction, a
      key factor in cardiovascular risk. We examined whether sympathetic activity is
      involved in the endothelial dysfunction caused by total sleep deprivation (TSD).
      DESIGN: TWO GROUPS: TSD (24-h wakefulness), using slowly rotating wheels, and
      wheel control (WC). PARTICIPANTS: Seven-month-old male Wistar rats.
      INTERVENTIONS: Pharmacological sympathectomy (reserpine, 5 mg/kg,
      intraperitoneal), nitric oxide synthase (NOS) inhibition (N (G)-nitro-L-arginine,
      20 mg/kg, intraperitoneally 30 min before experiment) and cyclooxygenase (COX)
      inhibition (indomethacin, 5 mg/kg, intraperitoneally 30 min before experiment).
      MEASUREMENTS AND RESULTS: In protocol 1, changes in heart rate (HR) and blood
      pressure were continuously recorded in the sympathectomized and non
      sympathectomized rats. Blood pressure and HR increased during TSD in non
      sympathectomized rats. In protocol 2, changes in skin blood flow (vasodilation)
      were assessed in the sympathectomized and non-sympathectomized rats using laser
      Doppler flowmetry coupled with iontophoretic delivery of acetylcholine (ACh),
      sodium nitroprusside (SNP), and anodal and cathodal currents. ACh- and cathodal
      current-induced vasodilations were significantly attenuated after TSD in non
      sympathectomized and sympathectomized rats (51% and 60%, respectively). In
      protocol 3, ACh-induced vasodilation was attenuated after NOS and COX inhibition
      (66% and 49%, respectively). Cathodal current-induced vasodilation decreased by
      40% after COX inhibition. In TSD compared to WC a decrease in ACh-induced
      vasodilation was still observed after COX inhibition. No changes in SNP- and
      anodal current-induced vasodilation were detected. CONCLUSION: These results
      demonstrate that total sleep deprivation induces a reduction in endothelial
      dependent vasodilation. This endothelial dysfunction is independent of blood
      pressure and sympathetic activity but associated with nitric oxide synthase and
      cyclooxygenase pathway alterations.

PMID- 24587569
TI  - Childhood parasomnias and psychotic experiences at age 12 years in a United
      Kingdom birth cohort.
AB  - STUDY OBJECTIVES: To examine associations between specific parasomnias and
      psychotic experiences in childhood. DESIGN: Birth cohort study. Information on
      the presence of frequent nightmares in children was obtained prospectively from
      mothers during multiple assessments conducted when children were aged between 2.5
      and 9 y. Children were interviewed at age 12 y about nightmares, night terrors,
      sleepwalking, and psychotic experiences (delusions, hallucinations, and thought
      interference) occurring in the previous 6 mo. SETTING: Assessments were completed
      in participants' homes or a University clinic within the UK. PATIENTS OR
      PARTICIPANTS: There were 6,796 children (3,462 girls, 50.9%) who completed the
      psychotic experiences interview. MEASUREMENTS AND RESULTS: Children who were
      reported by their mothers as experiencing frequent nightmares between 2.5 and 9 y
      of age were more likely to report psychotic experiences at age 12 y, regardless
      of sex, family adversity, emotional or behavioral problems, IQ and potential
      neurological problems (odds ratio (OR) = 1.16, [95% confidence intervals (CI) =
      1.00, 1.35], P = 0.049). Children reporting any of the parasomnias at age 12 y
      also had higher rates of concurrent psychotic experiences than those without such
      sleeping problems, when adjusting for all confounders (OR = 3.62 [95% CI = 2.57,
      5.11], P < 0.001). Difficulty getting to sleep and night waking were not found to
      be associated with psychotic experiences at age 12 y when controlling for
      confounders. CONCLUSION: Nightmares and night terrors, but not other sleeping
      problems, in childhood were associated with psychotic experiences at age 12
      years. These findings tentatively suggest that arousal and rapid eye movement
      forms of sleep disorder might be early indicators of susceptibility to psychotic
      experiences.

PMID- 24587570
TI  - Modafinil improves real driving performance in patients with hypersomnia: a
      randomized double-blind placebo-controlled crossover clinical trial.
AB  - STUDY OBJECTIVE: Patients with excessive daytime sleepiness (EDS) are at high
      risk for driving accidents, and physicians are concerned by the effect of
      alerting drugs on driving skills of sleepy patients. No study has up to now
      investigated the effect of modafinil (a reference drug to treat EDS in patients
      with hypersomnia) on on-road driving performance of patients suffering from
      central hypersomnia. The objective is to evaluate in patients with central
      hypersomnia the effect of a wake-promoting drug on real driving performance and
      to assess the relationship between objective sleepiness and driving performance.
      DESIGN AND PARTICIPANTS: Randomized, crossover, double-blind placebo-controlled
      trial conducted among 13 patients with narcolepsy and 14 patients with idiopathic
      hypersomnia. Patients were randomly assigned to receive modafinil (400 mg) or
      placebo for 5 days prior to the driving test. Each condition was separated by at
      least 3 weeks of washout. MEASUREMENTS: Mean number of Inappropriate Line
      Crossings, Standard Deviation of Lateral Position of the vehicle and mean sleep
      latency in the Maintenance of Wakefulness Test were assessed. RESULTS: Modafinil
      reduced the mean number of Inappropriate Line Crossings and Standard Deviation of
      Lateral Position of the vehicle compared to placebo (F(1,25) = 4.88, P < 0.05 and
      F(1,25) = 3.87, P = 0.06 tendency). Mean sleep latency at the Maintenance of
      Wakefulness Test significantly correlated with the mean number of Inappropriate
      Line Crossings (r = -0.41, P < 0.001). CONCLUSIONS: Modafinil improves driving
      performance in patients with narcolepsy and idiopathic hypersomnia. The
      Maintenance of Wakefulness Test is a suitable clinical tool to assess fitness to
      drive in this population.

PMID- 24587571
TI  - Residual effects of low-dose sublingual zolpidem on highway driving performance
      the morning after middle-of-the-night use.
AB  - STUDY OBJECTIVE: To evaluate next-morning driving performance after middle-of-the
      night use of zolpidem 3.5 mg in a buffered sublingual formulation (ZST). DESIGN:
      Single-center, four-period, randomized, double-blind, placebo-controlled,
      crossover study. SETTING: Maastricht University, The Netherlands. PARTICIPANTS:
      Forty healthy volunteers (20 females). INTERVENTIONS: Single dose of ZST
      administered in the middle of the night at 3 and 4 h before driving, zopiclone
      7.5 mg at bedtime 9 h before driving, and placebo. MEASUREMENTS: Performance in a
      100-km standardized highway driving test in normal traffic measuring standard
      deviation of lateral position (SDLP) - an index of weaving. Drug-placebo changes
      in SDLP > 2.5 cm were considered to reflect clinically relevant driving
      impairment. RESULT: For ZST, Max McNemar symmetry analyses showed that the
      proportion of drivers classified as impaired was increased 3 h after dosing (P <
      0.012), but not 4 h after dosing. Mean increases in SDLP from placebo, although
      statistically significant, were small (1.46 cm [P < 0.0001] at 3 h and 0.83 cm [P
      = 0.0174] at 4 h). The morning after zopiclone, 45% of the drivers were
      classified as impaired with a mean increase in SDLP of 2.46 cm (P < 0.0001).
      There were no significant sex differences in effects of ZST and zopiclone.
      CONCLUSION: Zolpidem 3.5 mg in a buffered sublingual formulation has a minimal
      risk of impairing driving performance in the morning >= 4 hours after middle-of
      the night use. When taken 3 hours before driving, the drug may have impairing
      effects so caution should be exercised if medication is taken other than as
      indicated. CLINICAL TRIAL INFORMATION: ClinicalTrials.gov Identifier:
      NCT01106859; Trial Name: Driving Performance After Middle of the Night
      Administration of 3.5 mg Zolpidem Tartrate Sublingual Tablet;
      http://clinicaltrials.gov/ct2/show/NCT01106859.

PMID- 24587572
TI  - Respiratory-related leg movements and their relationship with periodic leg
      movements during sleep.
AB  - STUDY OBJECTIVES: To describe the time structure of leg movements (LM) in
      obstructive sleep apnea (OSA) syndrome, in order to advance understanding of
      their clinical significance. LOCATION: Sleep Research Centre, Oasi Institute
      (IRCCS), Troina, Italy. SETTING: Sleep laboratory. PATIENTS: Eighty-four patients
      (16 females, 68 males, mean age 55.1 y, range 29-74 y). METHODS: Respiratory
      related leg movements (RRLM) and those unrelated to respiratory events (NRLM)
      were examined within diagnostic polysomnograms alone and together for their
      distributions within the sleep period and for their periodicity. MEASUREMENTS AND
      RESULTS: Patients with OSA and RRLM exhibited more periodic leg movements in
      sleep (PLMS), particularly in NREM sleep. A gradual decrease in number of NRLM
      across the sleep period was observed in patients with RRLM. This pattern was less
      clear for RRLM. Frequency histograms of intermovement intervals of all LMs in
      patients with RRLM showed a prominent first peak at 4 sec, and a second peak at
      approximately 24 sec coincident with that of PLMS occurring in the absence of
      OSA. A third peak of lowest amplitude was the broadest with a maximum at
      approximately 42 sec. In patients lacking RRLM, NRLM were evident with a single
      peak at 2-4 sec. A stepwise linear regression analysis showed that, after
      controlling for a diagnosis of restless legs syndrome and apnea-hypopnea index,
      PLMS remained significantly associated with RRLM. CONCLUSION: The time structure
      of leg movements occurring in conjunction with respiratory events exhibit
      features of periodic leg movements in sleep occurring alone, only with a
      different and longer period. This brings into question the validity, both
      biologic and clinical, of scoring conventions with their a priori exclusion from
      consideration as periodic leg movements in sleep.

PMID- 24587573
TI  - Musculoskeletal sensitization and sleep: chronic muscle pain fragments sleep of
      mice without altering its duration.
AB  - STUDY OBJECTIVES: Musculoskeletal pain in humans is often associated with poor
      sleep quality. We used a model in which mechanical hypersensitivity was induced
      by injection of acidified saline into muscle to study the impact of
      musculoskeletal sensitization on sleep of mice. DESIGN: A one month pre-clinical
      study was designed to determine the impact of musculoskeletal sensitization on
      sleep of C57BL/6J mice. METHODS: We instrumented mice with telemeters to record
      the electroencephalogram (EEG) and body temperature. We used an established model
      of musculoskeletal sensitization in which mechanical hypersensitivity was induced
      using two unilateral injections of acidified saline (pH 4.0). The injections were
      given into the gastrocnemius muscle and spaced five days apart. EEG and body
      temperature recordings started prior to injections (baseline) and continued for
      three weeks after musculoskeletal sensitization was induced by the second
      injection. Mechanical hypersensitivity was assessed using von Frey filaments at
      baseline (before any injections) and on days 1, 3, 7, 14, and 21 after the second
      injection. RESULTS: Mice injected with acidified saline developed bilateral
      mechanical hypersensitivity at the hind paws as measured by von Frey testing and
      as compared to control mice and baseline data. Sleep during the light period was
      fragmented in experimental mice injected with acidified saline, and EEG spectra
      altered. Musculoskeletal sensitization did not alter the duration of time spent
      in wakefulness, non-rapid eye movement sleep, or rapid eye movement sleep.
      CONCLUSIONS: Musculoskeletal sensitization in this model results in a distinct
      sleep phenotype in which sleep is fragmented during the light period, but the
      overall duration of sleep is not changed. This study suggests the consequences of
      musculoskeletal pain include sleep disruption, an observation that has been made
      in the clinical literature but has yet to be studied using preclinical models.

PMID- 24587574
TI  - Sleep fragmentation exacerbates mechanical hypersensitivity and alters subsequent
      sleep-wake behavior in a mouse model of musculoskeletal sensitization.
AB  - STUDY OBJECTIVES: Sleep deprivation, or sleep disruption, enhances pain in human
      subjects. Chronic musculoskeletal pain is prevalent in our society, and
      constitutes a tremendous public health burden. Although preclinical models of
      neuropathic and inflammatory pain demonstrate effects on sleep, few studies focus
      on musculoskeletal pain. We reported elsewhere in this issue of SLEEP that
      musculoskeletal sensitization alters sleep of mice. In this study we hypothesize
      that sleep fragmentation during the development of musculoskeletal sensitization
      will exacerbate subsequent pain responses and alter sleep-wake behavior of mice.
      DESIGN: This is a preclinical study using C57BL/6J mice to determine the effect
      on behavioral outcomes of sleep fragmentation combined with musculoskeletal
      sensitization. METHODS: Musculoskeletal sensitization, a model of chronic muscle
      pain, was induced using two unilateral injections of acidified saline (pH 4.0)
      into the gastrocnemius muscle, spaced 5 days apart. Musculoskeletal sensitization
      manifests as mechanical hypersensitivity determined by von Frey filament testing
      at the hindpaws. Sleep fragmentation took place during the consecutive 12-h light
      periods of the 5 days between intramuscular injections. Electroencephalogram
      (EEG) and body temperature were recorded from some mice at baseline and for 3
      weeks after musculoskeletal sensitization. Mechanical hypersensitivity was
      determined at preinjection baseline and on days 1, 3, 7, 14, and 21 after
      sensitization. Two additional experiments were conducted to determine the
      independent effects of sleep fragmentation or musculoskeletal sensitization on
      mechanical hypersensitivity. RESULTS: Five days of sleep fragmentation alone did
      not induce mechanical hypersensitivity, whereas sleep fragmentation combined with
      musculoskeletal sensitization resulted in prolonged and exacerbated mechanical
      hypersensitivity. Sleep fragmentation combined with musculoskeletal sensitization
      had an effect on subsequent sleep of mice as demonstrated by increased numbers of
      sleep-wake state transitions during the light and dark periods; changes in
      nonrapid eye movement (NREM) sleep, rapid eye movement sleep, and wakefulness;
      and altered delta power during NREM sleep. These effects persisted for at least 3
      weeks postsensitization. CONCLUSIONS: Our data demonstrate that sleep
      fragmentation combined with musculoskeletal sensitization exacerbates the
      physiological and behavioral responses of mice to musculoskeletal sensitization,
      including mechanical hypersensitivity and sleep-wake behavior. These data
      contribute to increasing literature demonstrating bidirectional relationships
      between sleep and pain. The prevalence and incidence of insufficient sleep and
      pathologies characterized by chronic musculoskeletal pain are increasing in the
      United States. These demographic data underscore the need for research focused on
      insufficient sleep and chronic pain so that the quality of life for the millions
      of individuals with these conditions may be improved.

PMID- 24587575
TI  - Role of adenosine and the orexinergic perifornical hypothalamus in sleep
      promoting effects of ethanol.
AB  - STUDY OBJECTIVES: Strong clinical and preclinical evidence suggests that acute
      ethanol promotes sleep. However, very little is known about how and where ethanol
      acts to promote sleep. We hypothesized that ethanol may induce sleep by
      increasing extracellular levels of adenosine and inhibiting orexin neurons in the
      perifornical hypothalamus. DESIGN: Experiments 1 and 2: Within-Subject Design;
      Experiment 3: Between-Subject Design. SETTING: N/A. PATIENTS OR PARTICIPANTS:
      N/A. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Using adult male Sprague
      Dawley rats as our animal model, we performed three experiments to test our
      hypothesis. Our first experiment examined the effect of A1 receptor blockade in
      the orexinergic perifornical hypothalamus on sleep- promoting effects of ethanol.
      Bilateral microinjection of the selective A1 receptor antagonist 1,3-dipropyl-8
      phenylxanthine (500 MUM; 250 nL/side) into orexinergic perifornical hypothalamus
      significantly reduced nonrapid eye movement sleep with a concomitant increase in
      wakefulness, suggesting that blockade of adenosine A1 receptor attenuates ethanol
      induced sleep promotion. Our second experiment examined adenosine release in the
      orexinergic perifornical hypothalamus during local ethanol infusion. Local
      infusion of pharmacologically relevant doses of ethanol significantly and dose
      dependently increased adenosine release. Our final experiment used c-Fos
      immunohistochemistry to examine the effects of ethanol on the activation of
      orexin neurons. Acute ethanol exposure significantly reduced the number of orexin
      neurons containing c-Fos, suggesting an inhibition of orexin neurons after
      ethanol intake. CONCLUSIONS: Based on our results, we believe that ethanol
      promotes sleep by increasing adenosine in the orexinergic perifornical
      hypothalamus, resulting in A1 receptor-mediated inhibition of orexin neurons.

PMID- 24587578
TI  - Sleep cyclic alternating pattern in otherwise healthy overweight school-age
      children.
AB  - STUDY OBJECTIVES: To compare sleep microstructure (cyclic alternating pattern,
      CAP) characteristics in otherwise healthy overweight (OW) and normal weight (NW)
      children. DESIGN: Polysomnographic cross-sectional study. SETTING: Sleep
      laboratory. PARTICIPANTS: Fifty-eight (26 NW and 32 OW) 10-year-old children.
      INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Participants were part of a
      longitudinal study beginning in infancy and free of sleep disorders. Groups were
      based on body-mass index (BMI) z-score. From polysomnographic overnight
      recordings, sleep-waking states were scored according to international criteria.
      CAP analysis was performed visually during NREM sleep. Conventional sleep
      parameters were similar between groups. BMI was positively related to CAP rate
      and CAP sequences but inversely related to CAP B phase duration. Differences
      between groups were confined to slow-wave sleep (SWS), with OW children showing
      higher CAP rate, CAP cycles, and CAP A1 number and index and shorter CAP cycles
      and B phase duration. They also showed more CAP class intervals shorter than 30
      s, and a suggestive trend for fewer intervals longer than 30 s. CONCLUSIONS:
      Cyclic alternating pattern characteristics in children related to nutritional
      status and were altered in overweight subjects during slow-wave sleep. We suggest
      that the more frequent oscillatory pattern of electroencephalographic slow
      activity in overweight subjects might reflect less stable slow-wave sleep
      episodes.

PMID- 24587576
TI  - Increased use-dependent plasticity in chronic insomnia.
AB  - STUDY OBJECTIVES: During normal sleep several neuroplasticity changes occur, some
      of which are considered to be fundamental to strengthen memories. Given the
      evidence linking sleep to neuroplasticity, it is conceivable that individuals
      with chronic sleep disruption, such as patients with chronic insomnia (CI), would
      experience abnormalities in neuroplastic processes during daytime. Protocols
      testing use-dependent plasticity (UDP), one of the mechanisms underlying
      formation of motor memories traces, provide a sensitive measure to assess
      neuroplasticity in the context of motor training. DESIGN AND PARTICIPANTS: A well
      established transcranial magnetic stimulation (TMS) paradigm was used to evaluate
      the ability of patients with CI and age-matched good sleeper controls to undergo
      UDP. We also investigated the effect of insomnia on intracortical motor
      excitability measures reflecting GABAergic and glutamatergic mechanisms. SETTING:
      Human Brain Physiology Laboratory, Johns Hopkins Medical Institutions.
      MEASUREMENTS AND RESULTS: We found that patients with CI experienced increased
      UDP changes relative to controls. This effect was not due to differences in motor
      training. In addition, patients with CI showed enhanced intracortical
      facilitation relative to controls, in the absence of changes in intracortical
      inhibitory measures. CONCLUSION: This study provides the first evidence that
      patients with chronic insomnia have an increased plasticity response to physical
      exercise, possibly due to larger activation of glutamatergic mechanisms. This
      suggests a heightened state of neuroplasticity, which may reflect a form of
      maladaptive plasticity, similar to what has been described in dystonia patients
      and chronic phantom pain after amputation. These results could lead to
      development of novel treatments for chronic insomnia.

PMID- 24587579
TI  - Physiological mechanisms of upper airway hypotonia during REM sleep.
AB  - STUDY OBJECTIVES: Rapid eye movement (REM)-induced hypotonia of the major upper
      airway dilating muscle (genioglossus) potentially contributes to the worsening of
      obstructive sleep apnea that occurs during this stage. No prior human single
      motor unit (SMU) study of genioglossus has examined this possibility to our
      knowledge. We hypothesized that genioglossus SMUs would reduce their activity
      during stable breathing in both tonic and phasic REM compared to stage N2 sleep.
      Further, we hypothesized that hypopneas occurring in REM would be associated with
      coincident reductions in genioglossus SMU activity. DESIGN: The activity of
      genioglossus SMUs was studied in (1) neighboring epochs of stage N2, and tonic
      and phasic REM; and (2) during hypopneas occurring in REM. SETTING: Sleep
      laboratory. PARTICIPANTS: 29 subjects (38 +/- 13 y) (17 male). INTERVENTION:
      Natural sleep, including REM sleep and REM hypopneas. MEASUREMENT AND RESULTS:
      Subjects slept overnight with genioglossus fine-wire intramuscular electrodes and
      full polysomnography. Forty-two SMUs firing during one or more of stage N2, tonic
      REM, or phasic REM were sorted. Twenty inspiratory phasic (IP), 17 inspiratory
      tonic (IT), and five expiratory tonic (ET) SMUs were characterized. Fewer units
      were active during phasic REM (23) compared to tonic REM (30) and stage N2 (33).
      During phasic REM sleep, genioglossus IP and IT SMUs discharged at slower rates
      and for shorter durations than during stage N2. For example, the SMU peak
      frequency during phasic REM 5.7 +/- 6.6 Hz (mean +/- standard deviation) was less
      than both tonic REM 12.3 +/- 9.7 Hz and stage N2 16.1 +/- 10.0 Hz (P < 0.001).
      The peak firing frequencies of IP/IT SMUs decreased from the last breath before
      to the first breath of a REM hypopnea (11.8 +/- 10.9 Hz versus 5.7 +/- 9.4 Hz; P
      = 0.001). CONCLUSION: Genioglossus single motor unit activity is significantly
      reduced in REM sleep, particularly phasic REM. Single motor unit activity
      decreases abruptly at the onset of REM hypopneas.

PMID- 24587577
TI  - Sleep loss, circadian mismatch, and abnormalities in reorienting of attention in
      night workers with shift work disorder.
AB  - STUDY OBJECTIVES: Permanent night-shift workers may develop shift-work disorder
      (SWD). In the current study, we evaluated neurophysiological and behavioral
      indices of distractibility across times prior to the night shift (T1), during
      night hours (T2), and after acute sleep deprivation (T3) in permanent hospital
      night workers with and without SWD. METHODS: Ten asymptomatic night workers (NW)
      and 18 NW with SWD participated in a 25-h sleep deprivation study. Circadian
      phase was evaluated by dim-light salivary melatonin onset (DLMO). Objective
      sleepiness was evaluated using the Multiple Sleep Latency Test (MSLT).
      Electrophysiological distractibility was evaluated by brain event-related
      potentials (ERP), whereas behavioral distractibility was evaluated by performance
      on a visual task in an auditory-visual distraction paradigm. STATISTICAL
      ANALYSES: Comparisons of ERP results were performed by repeated-measures analysis
      of variance, and t-tests were used where appropriate. A Mann-Whitney U test was
      used for comparison of variables (MLST, Stanford Sleepiness Scale, and DLMO) that
      deviated from normal. RESULTS: First, in the SWD group, the reorienting
      negativity ERP amplitude was significantly attenuated compared to that in the NW
      group. Second, the SWD group had shorter MSLT during night shift hours (4.8 +/-
      4.9 min) compared to that in NW (7.8 +/- 3.7 min; U = 47; z = -2.1; P < 0.03).
      Third, NW with SWD had a DLMO at 20:27 +/- 5.0 h, whereas healthy NW had a DLMO
      at 05:00 +/- 3.4 h (U = 43.5; z = -2.22, P < 0.03). Finally, acute sleep
      deprivation impaired behavioral performance and the P3a ERP in both groups.
      CONCLUSIONS: Our results demonstrate specific deficits in neurophysiological
      activity in the attentional domain among the shift-work disorder group relative
      to night workers.

PMID- 24587580
TI  - The relationship between functional health literacy and obstructive sleep apnea
      and its related risk factors and comorbidities in a population cohort of men.
AB  - STUDY OBJECTIVES: To examine the relationship between functional health literacy
      (FHL) and obstructive sleep apnea (OSA), its diagnosis, related risk factors, and
      comorbidities. DESIGN: Population cohort study. SETTING: Adelaide, South
      Australia, 2011-12. PARTICIPANTS: 1,021 Men Androgen Inflammation Lifestyle
      Environment and Stress Study participants aged >= 40 years, of whom 627 were
      identified with OSA by self-report (n = 184 previously diagnosed) or with in-home
      polysomnography in 837 randomly selected participants without self-reported OSA
      (n = 443 previously undiagnosed). INTERVENTIONS: The Newest Vital Sign assessed
      FHL in 88% of participants. Full in-home unattended polysomnography (Embletta
      X100) was scored by 2007 AASM (alternative) criteria. MEASUREMENTS AND RESULTS:
      FHL was adequate in 75.3% (n = 122) of previously diagnosed and 68.3% (n = 261)
      of previously undiagnosed OSA. Not having a previous diagnosis was independently
      associated with inadequate FHL (odds ratio [OR]:2.84, 95% confidence interval
      [CI]:1.25-6.45) and workforce participation (OR = 2.04, 95% CI = 1.01-4.00), and
      inversely associated with previous snoring (OR = 0.48, 95% CI = 0.29-0.81),
      obesity (OR = 0.35, 95% CI = 0.15-0.81), and cardiovascular disease (OR = 0.45,
      95% CI = 0.24-0.85). In polysomnography participants, inadequate FHL was
      independently associated with previously undiagnosed OSA (OR = 2.43, 95% CI =
      1.40-4.20). In undiagnosed men, less than adequate FHL was independently
      associated with sedentary lifestyle (OR = 2.42, 95% CI = 1.36-4.29), and
      depression (OR = 2.50, 95% CI = 1.23-5.09) and inadequate FHL was associated with
      current smoking (OR = 2.87, 95% CI = 1.21-6.84). The depression association was
      attenuated after additional adjustment for comorbidities and general health (OR =
      2.04, 95% CI = 0.93-4.49, P = 0.076). In previously diagnosed OSA, less than
      adequate FHL was independently associated with cardiovascular disease (OR = 2.76,
      95% CI = 1.09-7.01). CONCLUSIONS: Limited functional health literacy was
      independently associated with obstructive sleep apnea (OSA), OSA diagnosis,
      lifestyle factors and comorbidities, highlighting the importance of developing
      and promoting national disease-specific health literacy policies.

PMID- 24587581
TI  - Sleep problems and hospitalization for self-harm: a 15-year follow-up of 9,000
      Norwegian adolescents. The Young-HUNT Study.
AB  - OBJECTIVES: To investigate the association between sleeping problems in
      adolescence and subsequent hospital admission for self-harm (SH). DESIGN:
      Prospective cohort study, linking health survey information on sleep problems to
      hospital-based patient records. SETTING: Residents of Nord-Trondelag County,
      Norway, aged 13-19 years in 1995-97. PATIENTS OR PARTICIPANTS: 10,202 adolescents
      were invited to participate in the Young-HUNT study; 8,983 (88%) completed the
      health survey. MEASUREMENTS AND RESULTS: 10% of participants reported
      difficulties initiating sleep, 4% reported early morning wakening. Ninety-eight
      participants (27% male) were hospitalized following SH over a mean 12 years
      follow-up. Difficulties initiating sleep/early morning wakening were associated
      with increased risk of SH (HR 2.11, 95% CI 1.29-3.46, sex- and age-adjusted)
      compared with no problems, yet coexistent symptoms of combined anxiety/depression
      explained most of the association with sleep problems (fully adjusted HR 1.19,
      95% CI 0.66-2.16). The HR of combined difficulties initiating sleep/early morning
      wakening differed in those with and without anxiety/depression at baseline (P
      interaction = 0.03); among those without caseness symptoms of anxiety/depression
      it was 5.58 (95% CI 2.02-15.40), while in those with caseness symptoms of
      anxiety/ depression it was 0.82 (95% CI 0.19-3.44). CONCLUSIONS: Sleep problems
      are common among Norwegian adolescents. The strong association between sleep
      problems and subsequent hospitalization for self-harm could mainly be related to
      coexistent symptoms of anxiety and depression. Prevention of adolescent sleep
      problems, anxiety and depression should be targeted when seeking to reduce and
      prevent self-harm.

PMID- 24587582
TI  - Preliminary functional MRI neural correlates of executive functioning and empathy
      in children with obstructive sleep apnea.
AB  - BACKGROUND: Pediatric obstructive sleep apnea (OSA) is associated with
      neurocognitive deficits. However, the neural substrates underlying such deficits
      remain unknown. METHODS: To examine executive control and emotional processing in
      OSA, 10 children age 7 to 11 y with polysomnographically diagnosed OSA and 7 age-
      and sex-matched controls underwent a color-word Stroop task and an empathy task
      consisting of dynamic visual scenarios depicting interpersonal harm or neutral
      actions in a magnetic resonance imaging (MRI) scanner. Functional MRI data were
      processed using MATLAB 7.12 with SPM8 for region of interest (ROI) analyses, and
      a general linear model was used with regressors for each trial type in each task.
      RESULTS: For the Stroop task, accuracy was similar in the two groups, with no
      differences in the effect of incongruency on success rates. OSA showed greater
      neural activity than controls in eight ROI clusters for incongruent versus
      congruent trials (P < 0.001). Within the a priori ROIs, the anterior cingulate
      cortex was significantly different between groups (P < 0.05). For perceiving harm
      versus neutral actions, ROI analysis revealed a significant correlation between
      apnea-hypopnea index and left amygdala activity in harm versus neutral actions (r
      = -0.71, P < 0.05). CONCLUSIONS: These results provide the first functional MRI
      evidence that cognitive and empathetic processing is influenced by obstructive
      sleep apnea (OSA) in children. Children with OSA show greater neural recruitment
      of regions implicated in cognitive control, conflict monitoring, and attentional
      allocation in order to perform at the same level as children without OSA. When
      viewing empathy-eliciting scenarios, the severity of OSA predicted less
      sensitivity to harm in the left amygdala.

PMID- 24587583
TI  - Traditional and nontraditional cardiovascular risk factors in comorbid insomnia
      and sleep apnea.
AB  - OBJECTIVES: Insomnia and sleep apnea frequently co-occur and are independently
      associated with an increased risk of cardiovascular disease, but little is known
      about cardiovascular disease risk among individuals with comorbid insomnia and
      sleep apnea. The current study examined traditional risk factors and a
      physiologic biomarker of cardiovascular risk in comorbid insomnia and sleep
      apnea. DESIGN: Community-based participatory research study. PARTICIPANTS: The
      sample comprised 795 participants without preexisting cardiovascular disease from
      the Heart Strategies Concentrating On Risk Evaluation (Heart SCORE) study.
      MEASUREMENTS AND RESULTS: Participants were assessed for symptoms of insomnia and
      sleep apnea risk, as well as for presence of obesity, smoking, a sedentary
      lifestyle, hypertension, dyslipidemia, and diabetes. Baseline resting brachial
      artery diameter was measured by B-mode ultrasonography. A total of 138
      participants (17.4%) met criteria for insomnia syndrome alone, 179 (22.5%) were
      at high risk for sleep apnea alone, 95 (11.9%) reported both insomnia syndrome
      and high sleep apnea risk, and 383 (48.2%) reported having neither insomnia nor
      sleep apnea symptoms Both high sleep apnea risk alone and comorbid insomnia and
      high sleep apnea risk groups had greater frequencies of obesity, sedentary
      lifestyle, hypertension, and three or more traditional cardiovascular risk
      factors and significantly larger brachial artery diameters than the insomnia
      alone group and those without insomnia or sleep apnea symptoms. No differences in
      traditional cardiovascular risk factors or brachial artery diameter were found
      between the high sleep apnea risk and comorbid groups. CONCLUSIONS: These
      findings suggest that sleep apnea is a major contributor to cardiovascular risk
      and co-occurring insomnia does not appear to add to this risk.

PMID- 24587584
TI  - Short and long sleep duration associated with race/ethnicity, sociodemographics,
      and socioeconomic position.
AB  - STUDY OBJECTIVES: Short and/or long sleep duration are associated with
      cardiometabolic disease risk and may be differentially experienced among
      minorities and the socioeconomically disadvantaged. The present study examined
      nationally representative data along multiple dimensions of race/ ethnicity and
      socioeconomic status. DESIGN: Cross-sectional. SETTING: Survey. PATIENTS OR
      PARTICIPANTS: 2007-2008 NHANES (N = 4,850). INTERVENTIONS: None. MEASUREMENTS AND
      RESULTS: Self-reported sleep duration was classified as very short (< 5 h), short
      (5-6 h), normative (7-8 h) and long (>= 9 h). Population-weighted multinomial
      logistic regression analyses examined race/ ethnicity, country of origin,
      language, income, education, health insurance, and food security, controlling for
      all others as well as age, sex, marital-status, and overall self-rated health.
      Outcome was self-reported sleep duration, relative to normative sleep duration.
      Blacks/African Americans were more likely than whites to report very short (OR =
      2.34, P < 0.001) and short (OR = 1.85, P < 0.001) sleep. Mexican Americans
      reported less long sleep (OR = 0.36, P = 0.032). Other Hispanics/ Latinos
      reported more very short sleep (OR = 2.69, P = 0.025). Asians/ Others reported
      more very short (OR = 3.99, P = 0.002) and short (OR = 2.08, P = 0.002) sleep.
      Mexico-born adults reported less short sleep (OR = 0.63, P = 0.042). Spanish-only
      speakers reported less very short sleep (OR = 0.32, P = 0.030). Lower income
      groups reported more very short sleep versus > $75,000. Compared to college
      graduates, increased very short sleep was seen among all lower education levels.
      Those with public insurance reported more very short (OR = 1.67, P = 0.31) and
      long (OR = 1.83, P = 0.011) sleep versus uninsured. Very low food security was
      associated with very short (OR = 1.86, P = 0.036) and short (OR = 1.44, P =
      0.047) sleep. CONCLUSIONS: Minority status and lower socioeconomic position were
      associated with shorter self-reported sleep durations.

PMID- 24587585
TI  - Childhood sleep duration and quality in relation to leptin concentration in two
      cohort studies.
AB  - STUDY OBJECTIVES: Poor sleep in childhood is associated with increased obesity
      risk, possibly by affecting appetite-regulating hormones such as leptin. We
      examined short- and long-term sleep duration and quality in relation to leptin in
      two US pediatric cohorts. DESIGN: Analysis of data from two prospective cohort
      studies. SETTING: Population-based. Adolescent polysomnography assessments
      performed in a clinical research unit. PATIENTS OR PARTICIPANTS: Children in
      Project Viva (n = 655) and adolescents in the Cleveland Children's Sleep & Health
      Study (n = 502). INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: In Project Viva,
      mothers reported average child sleep duration annually from infancy through age
      7, and we measured leptin at ages 3 and 7. In the Cleveland Children's Sleep &
      Health Study, we collected self-reported sleep duration, polysomnography-derived
      measures of sleep quality, and fasting leptin at ages 16-19. In sex-stratified
      linear regression analyses adjusted for sociodemographic characteristics and
      adiposity, chronic curtailed sleep was associated with lower leptin at age 7 in
      girls; a one-unit decrease in sleep score was associated with a 0.08 decrease in
      log leptin (95% CI: 0.01,0.15). The association was stronger in girls with
      greater adiposity (P = 0.01). Among adolescents, shorter sleep was associated
      with lower leptin in males; each one-hour decrease in sleep duration was
      associated with a 0.06 decrease in log leptin (95% CI: 0.00, 0.11). Sleep
      duration was not associated with leptin at other ages. Sleep quality indices were
      not associated with leptin. CONCLUSIONS: Our results suggest possible age
      specific sexual dimorphism in the influence of sleep on leptin, which may partly
      explain inconsistencies in the literature.

PMID- 24587586
TI  - Integrating the review of Gottlieb et al. with the SAS-CARE Study.

PMID- 24587587
TI  - Plasmode simulation for the evaluation of pharmacoepidemiologic methods in
      complex healthcare databases.
AB  - Longitudinal healthcare claims databases are frequently used for studying the
      comparative safety and effectiveness of medications, but results from these
      studies may be biased due to residual confounding. It is unclear whether methods
      for confounding adjustment that have been shown to perform well in small, simple
      nonrandomized studies are applicable to the large, complex pharmacoepidemiologic
      studies created from secondary healthcare data. Ordinary simulation approaches
      for evaluating the performance of statistical methods do not capture important
      features of healthcare claims. A statistical framework for creating replicated
      simulation datasets from an empirical cohort study in electronic healthcare
      claims data is developed and validated. The approach relies on resampling from
      the observed covariate and exposure data without modification in all simulated
      datasets to preserve the associations among these variables. Repeated outcomes
      are simulated using a true treatment effect of the investigator's choice and the
      baseline hazard function estimated from the empirical data. As an example, this
      framework is applied to a study of high versus low-intensity statin use and
      cardiovascular outcomes. Simulated data is based on real data drawn from Medicare
      Parts A and B linked with a prescription drug insurance claims database
      maintained by Caremark. Properties of the data simulated using this framework are
      compared with the empirical data on which the simulations were based. In
      addition, the simulated datasets are used to compare variable selection
      strategies for confounder adjustmentvia the propensity score, including high
      dimensional approaches that could not be evaluated with ordinary simulation
      methods. The simulated datasets are found to closely resemble the observed
      complex data structure but have the advantage of an investigator-specified
      exposure effect.

PMID- 24587588
TI  - The Effects of Self-Regulation and Self-Efficacy on Substance Use Abstinence.
AB  - Previous research found that self-regulation and self-efficacy were linked to
      substance use abstinence. The present study examined the relationships between
      changes in self-regulation and self-efficacy as predictors of substance use
      abstinence. A total of 150 adult individuals (62% female; M age = 37.1 SD = 8.1;
      38% male) in substance abuse recovery participated in a randomized, longitudinal
      study comparing a communal housing model versus usual aftercare. Both the change
      in self-regulation (p = .014) and the change in self-efficacy (p = .032) were
      significantly predictive of the likelihood of abstinence. Additionally, changes
      in self-regulation and self-efficacy were largely independent. These findings
      suggest future research for examining change in self-regulation and self-efficacy
      substance abuse research.

PMID- 24587590
TI  - The Composition and Drawdown of Wealth in Retirement.

PMID- 24587589
TI  - The Associations of Eating-related Attitudinal Balance with Psychological Well
      being and Eating Behaviors.
AB  - This study used balance theory to illuminate the relations of eating-related
      attitudinal consistency between self and friends to psychological well-being and
      eating behaviors. It was hypothesized that attitudinal inconsistency, relative to
      consistency, would predict lower well-being and poorer eating habits. A
      population-based sample of 2287 young adults participating in Project EAT-III
      (Eating Among Teens and Young Adults) completed measures of psychological well
      being, eating behaviors, and eating-related attitudes from the standpoint of self
      and friends. Of participants who cared about healthy eating, those who perceived
      that their friends did not care about healthy eating had lower well-being and
      less-healthy eating behaviors (fewer fruits and vegetables and more sugary
      beverages per day) than those who perceived that their friends cared about
      healthy eating. Conversely, among participants who did not care about healthy
      eating, those who perceived that their friends cared about healthy eating had
      lower well-being and less-healthy eating behaviors (more snacks per day) than
      those who perceived that their friends did not care about healthy eating. In
      accord with balance theory, young adults who perceived inconsistent eating
      attitudes between themselves and their friends had lower psychological well-being
      and generally less-healthy eating behaviors than people who perceived consistent
      eating attitudes.

PMID- 24587591
TI  - Methane Decomposition and Carbon Growth on Y2O3, Yttria-Stabilized Zirconia, and
      ZrO2.
AB  - Carbon deposition following thermal methane decomposition under dry and steam
      reforming conditions has been studied on yttria-stabilized zirconia (YSZ), Y2O3,
      and ZrO2 by a range of different chemical, structural, and spectroscopic
      characterization techniques, including aberration-corrected electron microscopy,
      Raman spectroscopy, electric impedance spectroscopy, and volumetric adsorption
      techniques. Concordantly, all experimental techniques reveal the formation of a
      conducting layer of disordered nanocrystalline graphite covering the individual
      grains of the respective pure oxides after treatment in dry methane at
      temperatures T >= 1000 K. In addition, treatment under moist methane conditions
      causes additional formation of carbon-nanotube-like architectures by partial
      detachment of the graphite layers. All experiments show that during carbon
      growth, no substantial reduction of any of the oxides takes place. Our results,
      therefore, indicate that these pure oxides can act as efficient nonmetallic
      substrates for methane-induced growth of different carbon species with
      potentially important implications regarding their use in solid oxide fuel cells.
      Moreover, by comparing the three oxides, we could elucidate differences in the
      methane reactivities of the respective SOFC-relevant purely oxidic surfaces under
      typical SOFC operation conditions without the presence of metallic constituents.

PMID- 24587592
TI  - Comparison of milk oligosaccharides between goats with and without the genetic
      ability to synthesize alphas1-casein.
AB  - Milk oligosaccharides (OS)-free complex carbohydrates-confer unique health
      benefits to the nursing neonate. Though human digestive enzymes cannot degrade
      these sugars, they provide nourishment to specific commensal microbes and act as
      decoys to prevent the adhesion of pathogenic micro-organisms to gastrointestinal
      cells. At present, the limited quantities of human milk oligosaccharides (HMO)
      impede research on these molecules and their potential applications in functional
      food formulations. Considerable progress has been made in the study of OS
      structures; however, the synthetic pathways leading to their synthesis in the
      mammary gland are poorly understood. Recent studies show that complex OS with
      fucose and N-acetyl neuraminic acid (key structural elements of HMO bioactivity)
      exist in goat milk. Polymorphisms in the CSN1S1 locus, which is responsible for
      synthesis of alphas1-casein, affect lipid and casein micelle structure in goat
      milk. The present study sought to determine whether CSN1S1 polymorphisms also
      influence goat milk oligosaccharide (GMO) production and secretion. The GMO
      compositions of thirty-two goat milk samples, half of which were from genotype
      A/A (alphas1-casein producers) and half from genotype O/O (alphas1-casein non
      producers), were determined with nanoflow liquid chromatography high-accuracy
      mass spectrometry. This study represents the most exhaustive characterization of
      GMO to date. A systematic and comprehensive GMO library was created,
      consolidating information available in the literature with the new findings.
      Nearly 30 GMO, 11 of which were novel, were confirmed via tandem mass
      spectrometric analyses. Six fucosylated OS were identified; 4 of these matched
      HMO compositions and three were identified for the first time in goat milk.
      Importantly, multivariate statistical analysis demonstrated that the OS profiles
      of the A/A and O/O genotype milks could be discriminated by the fucosylated OS.
      Quantitative analysis revealed that the goat milk samples contained 1.17 g/L of
      OS; however, their concentration in milks from A/A and O/O genotypes was not
      different. This study provides evidence of a genetic influence on specific OS
      biosynthesis but not total OS production. The presence of fucosylated GMO
      suggests that goat milk represents a potential source of bioactive milk OS
      suitable as a functional food ingredient.

PMID- 24587593
TI  - Comparison of gluten recovery in gluten-incurred buckwheat flour using different
      commercial test kits.
AB  - Recovery of gluten in buckwheat flour was evaluated as part of an effort to
      produce wheat-contaminated buckwheat flours that could be used as reference
      materials (RMs) for testing the presence of gluten in buckwheat. RMs of buckwheat
      containing 0, 20, 100 and 1000 ppm gluten were created and tested by ELISA. The
      Gluten-Check kit detected gluten accurately at all levels; RIDASCREEN and Biokits
      tests were accurate at 20 and 100 ppm levels, but at 1000 ppm both suffered from
      extraction saturation effect; Veratox kit read 60% higher for the 20 ppm RM
      (i.e., 31.9 ppm), but close to the target at 100 ppm RM; Veratox R5 kit showed
      low accuracy with around 30% recovery at 20 and 100 ppm and some 60% at 1000 ppm
      level. Overall, the results showed variations in recovery among different test
      kits which could have important implications in the accurate detection of gluten
      in buckwheat.

PMID- 24587594
TI  - Portable system for the detection of micromolar concentrations of glucose.
AB  - Glucose in non-invasively collected biofluids is generally in the micromolar
      range and thus, requires sensing methodologies capable of measuring glucose at
      these levels. Here, we present a small fluorometer system that can quantify
      glucose in the range of 0-5 MUM with resolution of ~0.07 MUM. It relies on the
      glucose binding protein (GBP) fluorescently labeled with two fluorophores.
      Fluorescence signals from the dual-labeled GBP are utilized in a ratiometric
      mode, making the measurements insensitive to variations in protein concentration
      and other systematic errors. Fluorescence is quantified by a miniature, dedicated
      ratiometric fluorometer that is powered via USB. Concentration is calculated
      using an ultra-mobile personal computer (UMPC). The whole system is designed to
      be pocket sized suitable for point-of-care or bedside applications. Test results
      suggest that the system is a promising tool for accurate measurements of low
      glucose concentrations (0.1-10 MUM) in biological samples.

PMID- 24587597
TI  - From the Editor's Desk.

PMID- 24587598
TI  - The Best is Yet to Come.

PMID- 24587599
TI  - Preeclampsia-eclampsia.
AB  - Preeclampsia and eclampsia are grave complications of pregnancy responsible for
      morbidity and mortality. National Eclampsia Registry of the FOGSI has helped in
      quantifying the magnanimity and also the clinical relevant pointers which can
      help in improving the health care delivery. Many complex pathogenic mechanisms
      are now implicated to be responsible for this disease rightfully called the
      GESTOSIS which means pregnancy going abnormal. Many preventive strategies have
      been suggested but only a few are scientifically proved to be useful. Early
      antenatal care, clinical risk assessment, biomarkers, close vigilance, calcium
      and nutritional supplementation are useful. 

PMID- 24587600
TI  - Comparison of Efficacy of Three Suture Materials, i.e., Poliglecaprone 25,
      Polyglactin 910, Polyamide, as Subcuticular Skin Stitches in Post-Cesarean Women:
      A Randomized Clinical Trial.
AB  - OBJECTIVES: To compare the efficacy of three suture materials, i.e.,
      poliglecaprone 25, polyglactin 910, and polyamide, as subcuticular skin stitches
      in post-cesarean women. STUDY DESIGN: This was a randomized clinical trial.
      POPULATION: The study was conducted in the department of obstetrics and
      gynecology of a tertiary institute, LTMMC, Sion, Mumbai, India. Only those women
      undergoing emergency cesarean section were included. METHODS: The study was
      conducted in the department of obstetrics and gynecology of a tertiary institute,
      LTMMC, Sion, Mumbai, India. 90 women undergoing emergency cesarean section were
      included and divided into three groups. In group 1, poliglecaprone 25 was used as
      subcuticular skin stitches; in group 2, polyglactin 910 was used as subcuticular
      skin stitches; and in group 3, polyamide was used as subcuticular skin stitches.
      RESULTS: Thirty percentage of the patients in group 3 had discomfort on day 10,
      while it was only 3.3 % in group 1. In group 1, 6.6 % patients had swelling and
      indurations, while it was 33.3 % in group 2 on day 4. Wound dehiscence was
      present in 3.3 % patients in group 1, 26.6 % in group 2, and 6.6 % in group 3.
      Regarding wound healing, 93.3 % patients had excellent wound healing in group 1,
      66.6 % in group 2, and 86.6 % in group 3. CONCLUSIONS: The results were almost
      similar with poliglecaprone and polyamide, except for discomfort which was
      present more in patients in group 3.

PMID- 24587596
TI  - Rapamycin attenuates endothelial apoptosis induced by low shear stress via mTOR
      and sestrin1 related redox regulation.
AB  - BACKGROUND: Studies indicate the dramatic reduction of shear stress (SS) within
      the rapamycin eluting stent (RES) segment of coronary arteries. It remains
      unclear about the role of rapamycin in endothelialization of stented arteries
      where SS becomes low. Since mTOR (mammalian target of rapamycin) pathway is
      involved in the antioxidative sestrins expression, we hypothesized that rapamycin
      attenuated low SS (LSS) induced endothelial dysfunction through mTOR and sestrin1
      associated redox regulation. METHODS AND RESULTS: To mimic the effect of LSS on
      the stented arteries, a parallel plate flow chamber was used to observe the
      interplay of LSS and rapamycin on endothelial cells (ECs). The results showed LSS
      significantly induced EC apoptosis which was mitigated by pretreatment of
      rapamycin. Rapamycin attenuated LSS induced reactive oxygen species (ROS) and
      reactive nitrogen species (RNS) production via prohibition of sestrin1
      downregulation. Activities of mTORC1 and mTORC2 were detected contradictorily
      modulated by LSS. Inhibition of rictor expression by target small interfering RNA
      (siRNA) transfection prohibited sestrin1 downregulation induced by LSS, but
      inhibition of raptor did not. CONCLUSIONS: Rapamycin may prohibit sestrin1
      downregulation through targeting mTORC2 in appeasing LSS induced EC oxidative
      apoptosis. Our results provide the in vitro evidence to explain the
      pathophysiology of RES stented arteries.

PMID- 24587595
TI  - H. pylori virulence factors: influence on immune system and pathology.
AB  - Helicobacter pylori is the most widespread chronic bacterial agent in humans and
      is well recognized for its association with ulcer disease and gastric cancer,
      with both representing major global health and socioeconomic issues. Given the
      high level of adaptation and the coevolution of this bacterium with its human
      host, a thorough and multidirectional view of the specific microbiological
      characteristics of this infection as well as the host physiology is needed in
      order to develop novel means of prevention of therapy. This review aims to
      pinpoint some of these potentially important angles, which have to be considered
      mutually when studying H. pylori's pathogenicity. The host's biological changes
      due to the virulence factors are a valuable pillar of H. pylori research as are
      the mechanisms by which bacteria provoke these changes. In this context,
      necessary adhesion molecules and significant virulence factors of H. pylori are
      discussed. Moreover, metabolism of the bacteria, one of the most important
      aspects for a better understanding of bacterial physiology and consequently
      possible therapeutic and prophylactic strategies, is addressed. On the other
      hand, we discuss the recent experimental proofs of the "hygiene hypothesis" in
      correlation with Helicobacter's infection, which adds another aspect of
      complexity to this infection. 

PMID- 24587601
TI  - Assessment of Frequency of Twin Pregnancy and Neonatal Outcome in Deliveries of
      Mo'tazedi Hospital, Kermanshah in 2004-2007.
AB  - INTRODUCTION: Twin pregnancy is a high-risk pregnancy with different prevalences
      in different regions of the world which is on the rise due to growing use of
      assisted reproductive technology. The objective of this study is to determine the
      frequency of twin pregnancy and the neonatal outcome of these pregnancies.
      MATERIALS AND METHODS: This is a descriptive-analytic study conducted in 2004
      2007 in Mo'tazedi Hospital, Kermanshah on 142 twin deliveries as well as the
      singleton deliveries before and after twin pregnancy as the control group. The
      required information, including maternal age, gestational age, newborn's gender,
      presentation of twins, birth weight, Apgar score, fetal anomalies, and neonatal
      mortality were extracted from medical files and analyzed statistically. FINDINGS:
      After assessment of 29,438 deliveries performed from 2004 to 2007, the frequency
      of twin pregnancy was found out to be 1 in 208 cases (48 %). The mean age of
      mothers was higher in twin pregnancies. The mean gestational age of twin
      pregnancy was 34.3 weeks. Apgar score and neonatal weight were significantly
      lower in twin pregnancy compared to singleton pregnancy (p < 0.001). Furthermore,
      visible anomalies and mortality were significantly higher in neonates born to
      twin pregnancies compared to singleton pregnancies (p < 0.0001 and p = 0.009,
      respectively). The ratio of male to female neonates was 1. CONCLUSION: This study
      indicated that twin pregnancy is a high-risk condition and entails greater
      neonatal complications compared to singleton pregnancy. Therefore, it is
      recommendable to have greater perinatal care and perform deliveries in well
      equipped centers under supervision of an obstetrician.

PMID- 24587602
TI  - A study to review sex ratio at birth and analyze preferences for the sex of the
      unborn.
AB  - OBJECTIVES: (1) To study the status of sex ratio at birth with increasing birth
      order, (2) To ascertain the relationship of declining sex ratio with respect to
      socio demographic factors. (3) To study outlook of patient towards sex
      preference, willingness to determine sex of the fetus, wish to terminate the
      pregnancy in case of unwanted sex of the baby. METHODS: This is the retrospective
      study done in the Department of Obstetrics and Gynaecology, Nowrosjee Wadia
      Maternity Hospital, Parel, Mumbai. The data was collected from the records
      maintained in Medical Record Department from January 2007 to December 2012 and
      were studied to determine the sex ratio as well as its relationship with the
      increasing parity. 95 % confidence interval for the sex ratios was calculated.
      RESULTS: Average sex ratio of 6 years was 908 females per 1,000 males. Sex ratio
      was 972 females per 1,000 males in primi para, which decreased to 879 females per
      1,000 males in second para, further reduced to 784 females per 1,000 males in
      third para and 864 females per 1,000 males in fourth para. CONCLUSION: The 'sex
      ratio at birth', defined as the number of girls born for every 1,000 boys born,
      is a more accurate and refined indicator of the extent of prenatal sex selection.

PMID- 24587603
TI  - Mutational Screening and Prenatal Diagnosis in Cornelia de Lange syndrome.
AB  - Phenotypic variability and the lack of a diagnostic marker have complicated the
      rapid diagnosis and genetic counseling for Cornelia de Lange syndrome (CdLS). The
      clinical features of CdLS are striking and easily recognizable by characteristic
      facial dysmorphism, upper-extremity malformations, hirsutism, cardiac defects,
      growth and cognitive retardation, and gastrointestinal abnormalities with severe
      mental retardation. The molecular diagnosis is essential for predicting prognosis
      and genetic counseling in the affected family, especially while planning the next
      pregnancy. We report here from India six cases of CdLS and how precise mutational
      screening in two cases helped in prenatal diagnosis and proved significant in
      prevention of recurrence in the affected family. 

PMID- 24587604
TI  - Correlation of amniotic fluid index with perinatal outcome.
AB  - OBJECTIVES: We aimed to evaluate the predictive value of amniotic fluid index
      (AFI) (<5) for adverse perinatal outcome in terms of cesarean section for fetal
      distress, birth weight, meconium staining, Apgar scores, and cord pH at birth.
      METHODS: This was a prospective study of 200 antenatal women booked at Ram
      Manohar Lohia (RML) Hospital during the years 2009-2011 with gestational age
      between 34 and 41 weeks. The women's history, clinical examination recorded, and
      AFI were measured and the perinatal outcome was compared between two groups,
      i.e., AFI < 5 and >5. RESULTS: The cesarean section rate for fetal distress and
      low birth weight babies, <2.5 kg, was higher in patients with oligohydramnios (p
      = 0.048, 0.001, respectively). There was no significant difference in meconium
      staining, Apgar score at 5 min <7, and cord pH at birth between the two groups (p
      = 0.881, 0.884, 0.764, respectively). CONCLUSIONS: Oligohydramnios has a
      significant correlation with cesarean section for fetal distress and low birth
      weight babies.

PMID- 24587605
TI  - Laparoscopic Gynae-oncological Procedures: Lessons Learnt After a Single
      Institution Audit of Complications and Their Management in 567 Consecutive
      Patients.
AB  - STUDY OBJECTIVE: To retrospectively evaluate the complications of the
      laparoscopic pelvic surgeries and to formulate the guidelines to avoid them.
      DESIGN: Retrospective study (Canadian Classification). SETTING: Advanced
      Laparoscopic Institute. PATIENTS: Nine hundred and seven operated for
      gynecological malignancies. INTERVENTION: Laparoscopic surgeries. MEASUREMENTS
      AND MAIN RESULTS: 567 women suffering from different pelvic conditions were
      studied in a period of 60 months. The median age of the patient was 35 (11-80).
      Complications occurred in 32 patients (32/567, 5.5 %). The overall incidence of
      urinary tract injury in all the advanced cases at our institute was 2.1 %
      (12/567). The incidence of bowel injury at our center was 1.76 %. The incidence
      of vascular injury at our institute was 1.76 % (10/567). CONCLUSION: Laparoscopic
      complications are different than those seen following open surgeries.
      Anticipation, early recognition, and timely intervention help to reduce
      morbidity. Laparoscopic management of complications is possible. Formulating
      standard guidelines can help to avoid many such complications.

PMID- 24587606
TI  - Clinical scoring system to detect malignant and premalignant vulval lesions.
AB  - OBJECTIVE: To construct a simple clinical scoring system for evaluation of vulval
      lesions that will be helpful in clinically detecting the premalignant or
      malignant lesions of vulva. METHODS: Seventy women referred for vulval
      examination at a tertiary care centre in north India were examined over a period
      of 2 years. Biopsy was performed in 66 consenting women. Association of high
      grade vulval lesion with various clinical parameters such as age, duration of
      symptoms, presenting complaints, the presence of depigmentation, ulceration,
      hyperkeratosis, acetowhite changes on acetic acid application, asymmetrical
      distribution of the lesion, surface elevation on naked eye or colposcopy,
      induration on palpation and toluidine blue stain retention was studied. The
      significantly associated factors were assigned a value of 0 or 1 depending on
      whether they were present or absent. Score was then formulated for detection of
      high-grade lesion defined as moderate to severe dysplasia and early malignancy.
      MAIN OUTCOME MEASURES: Histopathology. RESULTS: Out of the various parameters
      that were studied, duration of symptoms more than 6 months, hyperkeratosis,
      asymmetrical distribution of the lesion, surface elevation on naked eye or
      colposcopy, induration on palpation and positive toluidine blue stain retention
      of the lesion were found to be significantly associated with a malignant or
      premalignant lesion. It was found that a score of equal to or greater than 3/6
      was significantly associated with a malignant or premalignant lesion. CONCLUSION:
      This simple scoring system has a potential to identify the high-grade lesions and
      can be used to identify the vulval lesion requiring a biopsy or further referral
      to higher centre.

PMID- 24587607
TI  - Serum Levels of Anti-histone and Anti-double-Strand DNA Antibodies Before and
      After Laparoscopic Ovarian Drilling in Women with Polycystic Ovarian Syndrome.
AB  - OBJECTIVES: To determine the serum levels of anti-dsDNA, anti-histone, and anti
      nucleosome antibodies after laparoscopic ovarian electrocauterization in patients
      with polycystic ovarian syndrome (PCOS). METHODS: Our study was performed on 35
      patients with PCOS resistant to medical therapy, 35 patients with unexplained
      infertility, and 35 healthy fertile individuals. Patients with PCOS underwent
      laparoscopic electrocauterization while those with unexplained infertility
      underwent diagnostic laparoscopy. Serum levels of anti-dsDNA, anti-histone, and
      anti-nucleosome antibodies were measured at baseline and 1 month after operation
      and were compared between groups. RESULT: Baseline characteristics were similar
      between groups. Patients with PCOS had significantly higher levels of anti-dsDNA
      compared to unexplained infertility (p < 0.001) and control groups (p = 0.001).
      Anti-histone antibodies were higher in PCOS group compared to control group (p =
      0.001). In those patients suffering from PCOS, anti-histone antibody increased
      significantly 1 month after ovarian electrocauterization (p = 0.017). Similarly,
      serum levels of anti-nucleosome antibodies increased significantly 1 month after
      operation (p < 0.001). CONCLUSION: Laparoscopic ovarian electrocauterization in
      patients with PCOS results in increased levels of anti-histone and anti
      nucleosome antibodies. Anti-dsDNA, anti-histone, and anti-nucleosome antibodies
      also increase after diagnostic laparoscopy in those with unexplained infertility.
      Patients with PCOS have higher levels of anti-dsDNA and anti-histone antibodies
      compared to those with unexplained infertility and healthy fertile subjects.

PMID- 24587608
TI  - Gynecological morbidities in a population of rural postmenopausal women in
      pondicherry: uncovering the hidden base of the iceberg.
AB  - RESEARCH QUESTIONS: (1) What is the prevalence of common gynecological
      morbidities and gynecological symptoms among postmenopausal women in rural
      Pondicherry? (2) What are the determinants of postmenopausal gynecological
      morbidities? METHODS:  STUDY DESIGN: Community-based cross-sectional study.
      SETTING: Two villages in Pondicherry, India. PARTICIPANTS: All postmenopausal
      women aged 50 years and above in the two villages. The participants were
      interviewed in their households and motivated for examination. By adopting social
      mobilization strategies coupled with a "Geriatric-friendly" camp approach, 239
      eligible women completed gynecological examination. Bivariate analysis of
      association between gynecological morbidities and its determinants was done using
      Chi square test. RESULTS: Among the study population, the prevalence of at least
      one gynecological morbidity was 44.4 % (CI 38.0-50.8), whereas the prevalence of
      at least one gynecological symptom was only 25.9 % (CI 20.3-31.5). Genital
      prolapse was the most common morbidity which was present in 18.8 % of women. On
      bivariate analysis, the prevalence of gynecological morbidity was significantly
      associated with a lower socio-economic status and associated chronic co
      morbidities. CONCLUSIONS: Postmenopausal women harbor a considerable magnitude of
      gynecological morbidities, and approaches such as geriatric-friendly camps can
      help in uncovering the full spectrum of gynecological morbidities.

PMID- 24587610
TI  - A Pregnant Woman with Lactococcus lactis Meningitis: To Treat or Not to Treat?

PMID- 24587609
TI  - No Superiority of Granisetron Over Metoclopramide in Prevention of Post-operative
      Nausea and Vomiting: A Randomized Clinical Trial.
AB  - PURPOSE: Post-operative nausea and vomiting (PONV) is considered as one of the
      most disturbing sequels of surgeries under general anesthesia, which if not
      controlled appropriately increases post-operative morbidity, nursing burden, and
      general healthcare costs. In this study, we compared granisetron with its brand
      Kytril((r)) and also with metoclopramide regarding PONV management. METHODS: A
      total of 180 obstetrics and gynecology patients who underwent surgeries under
      general anesthesia participated in this prospective study at the Dr. Shariati
      Teaching Hospital, Tehran, Iran. The patients were randomly assigned to single
      dose generic granisetron (40 mcg/kg), Kytril((r)) (40 mcg/kg), or metoclopramide
      (0.2 mg/kg) at the end of the surgery. Two episodes of emetic symptoms (nausea
      and vomiting) were recorded by a gynecologist who had no knowledge of which
      treatment each patient had received. This gynecologist observed the patients at
      three different intervals: 0-6, 6-12, and 12-18 h post-surgery. RESULTS: One
      hundred and thirty-seven patients (76.1 %) underwent hysterectomy and 40 patients
      (22.2 %) underwent myomectomy. Each group consisted of 60 patients (33 %). The
      incidence of vomiting in the first 6, 12, and 18 h post-surgery was 22, 15.2, and
      13.3 % for granisetron; 18.6, 10, and 8.3 % for Kytril; and 22, 11.9, and 5 % for
      generic metoclopramide, respectively. There was no significant difference in the
      incidence of PONV with any of these agents. CONCLUSIONS: All three anti-nausea
      and vomiting agents, granisetron, its brand (Kytril), and generic metoclopramide,
      have a similar effect to manage PONV in obstetrics and gynecological surgeries.
      Trial registration This trial is registered with www.irct.ir, number
      IRCT201010134927N1.

PMID- 24587611
TI  - Primary ovarian lymphoma: a case report and review of literature.

PMID- 24587612
TI  - Malignant transformation of leiomyoma of uterus to leiomyosarcoma with metastasis
      to ovary.

PMID- 24587613
TI  - Primary endometrioid carcinoma of the broad ligament: a rare case report.

PMID- 24587614
TI  - Unruptured Ampullary Ectopic Pregnancy at 16-week Period of Gestation with Live
      Fetus.

PMID- 24587615
TI  - OptiSpec((r)): Manufacturer: Utah Medical Products, INC, USA/Model No: LITE
      WS/OptiSpec((r)) Disposable Clip-On Gynecology Light, Sterile 25/BOX.

PMID- 24587616
TI  - Multifunctional to multistage delivery systems: The evolution of nanoparticles
      for biomedical applications.
AB  - Nanomaterials are advancing in several directions with significant progress being
      achieved with respect to their synthesis, functionalization and biomedical
      application. In this review, we will describe several classes of prototypical
      nanocarriers, such as liposomes, silicon particles, and gold nanoshells, in terms
      of their individual function as well as their synergistic use. Active and passive
      targeting, photothermal ablation, and drug controlled release constitute some of
      the crucial functions identified to achieve a medical purpose. Current
      limitations in targeting, slow clearance, and systemic as well as local toxicity
      are addressed in reference to the recent studies that attempted to comprehend and
      solve these issues. The demand for a more sophisticated understanding of the
      impact of nanomaterialson the body and of their potential immune response
      underlies this discussion. Combined components are then discussed in the setting
      of multifunctional nanocarriers, a class of drug delivery systems we envisioned,
      proposed, and evolved in the last 5 years. In particular, our third generation of
      nanocarriers, the multistage vectors, usher in the new field of nanomedicine by
      combining several components onto multifunctional nanocarriers characterized by
      emerging properties and able to achieve synergistic effects.

PMID- 24587617
TI  - Helicobacter pylori infection and extragastric disorders in children: a critical
      update.
AB  - Helicobacter pylori (H. pylori) is a highly prevalent, serious and chronic
      infection that has been associated causally with a diverse spectrum of
      extragastric disorders including iron deficiency anemia, chronic idiopathic
      thrombocytopenic purpura, growth retardation, and diabetes mellitus. The inverse
      relation of H. pylori prevalence and the increase in allergies, as reported from
      epidemiological studies, has stimulated research for elucidating potential
      underlying pathophysiological mechanisms. Although H. pylori is most frequently
      acquired during childhood in both developed and developing countries, clinicians
      are less familiar with the pediatric literature in the field. A better
      understanding of the H. pylori disease spectrum in childhood should lead to
      clearer recommendations about testing for and treating H. pylori infection in
      children who are more likely to develop clinical sequelae. A further clinical
      challenge is whether the progressive decrease of H. pylori in the last decades,
      abetted by modern clinical practices, may have other health consequences. 

PMID- 24587618
TI  - Structural and functional aspects of the Helicobacter pylori secretome.
AB  - Proteins secreted by Helicobacter pylori (H. pylori), an important human pathogen
      responsible for severe gastric diseases, are reviewed from the point of view of
      their biochemical characterization, both functional and structural. Despite the
      vast amount of experimental data available on the proteins secreted by this
      bacterium, the precise size of the secretome remains unknown. In this review, we
      consider as secreted both proteins that contain a secretion signal for the
      periplasm and proteins that have been detected in the external medium in in vitro
      experiments. In this way, H. pylori's secretome appears to be composed of
      slightly more than 160 proteins, but this number must be considered very
      cautiously, not only because the definition of secretome itself is ambiguous but
      also because the included proteins were observed as secreted in in vitro
      experiments that were not representative of the environmental situation in vivo.
      The proteins that appear to be secreted can be grouped into different classes:
      enzymes (48 proteins), outer membrane proteins (43), components of flagella (11),
      members of the cytotoxic-associated genes pathogenicity island or other toxins (8
      and 5, respectively), binding and transport proteins (9), and others (11). A
      final group, which includes 28 members, is represented by hypothetical
      uncharacterized proteins. Despite the large amount of data accumulated on the H.
      pylori secretome, a considerable amount of work remains to reach a full
      comprehension of the system at the molecular level. 

PMID- 24587619
TI  - Helicobacter pylori infection: host immune response, implications on gene
      expression and microRNAs.
AB  - Helicobacter pylori (H. pylori) infection is the most common bacterial infection
      worldwide. Persistent infection of the gastric mucosa leads to inflammatory
      processes and may remain silent for decades or progress causing more severe
      diseases, such as gastric adenocarcinoma. The clinical consequences of H. pylori
      infection are determined by multiple factors, including host genetic
      predisposition, gene regulation, environmental factors and heterogeneity of H.
      pylori virulence factors. After decades of studies of this successful
      relationship between pathogen and human host, various mechanisms have been
      elucidated. In this review, we have made an introduction on H. pylori infection
      and its virulence factors, and focused mainly on modulation of host immune
      response triggered by bacteria, changes in the pattern of gene expression in H.
      pylori-infected gastric mucosa, with activation of gene transcription involved in
      defense mechanisms, inflammatory and immunological response, cell proliferation
      and apoptosis. We also highlighted the role of bacteria eradication on gene
      expression levels. In addition, we addressed the recent involvement of different
      microRNAs in precancerous lesions, gastric cancer, and inflammatory processes
      induced by bacteria. New discoveries in this field may allow a better
      understanding of the role of major factors involved in the pathogenic mechanisms
      of H. pylori. 

PMID- 24587620
TI  - A review of Helicobacter pylori diagnosis, treatment, and methods to detect
      eradication.
AB  - Helicobacter pylori (H. pylori) affects nearly half of the world's population
      and, thus, is one of the most frequent and persistent bacterial infections
      worldwide. H. pylori is associated with peptic ulcer disease, gastric ulcers,
      mucosa-associated lymphoid tissue lymphoma, and gastric cancer. Various
      diagnostic methods exist to detect infection, and the choice of one method or
      another depends on several factors, such as accessibility, advantages and
      disadvantages of each method, cost, and the age of patients. Once H. pylori
      infection is diagnosed, the clinician decides whether treatment is necessity,
      according to the patient's clinical condition. Typically, eradication of H.
      pylori is recommended for treatment and prevention of the infection. Cure rates
      with the standard triple therapy are acceptable, and effective quadruple
      therapies, sequential therapies, and concomitant therapies have been introduced
      as key alternatives to treat H. pylori infection. In this work, we review the
      main diagnostic methods used to identify H. pylori infection and to confirm
      eradication of infection. In addition, key factors related to treatment are
      reviewed. 

PMID- 24587623
TI  - Helicobacter pylori-related chronic gastritis as a risk factor for colonic
      neoplasms.
AB  - To summarize the current views and insights on associations between Helicobacter
      pylori (H. pylori)-related chronic gastritis and colorectal neoplasm, we reviewed
      recent studies to clarify whether H. pylori infection/H. pylori-related chronic
      gastritis is associated with an elevated risk of colorectal neoplasm. Recent
      studies based on large databases with careful control for confounding variables
      have clearly demonstrated an increased risk of colorectal neoplasm associated
      with H. pylori infection. The correlation between H. pylori-related chronic
      atrophic gastritis (CAG) and colorectal neoplasm has only been examined in a
      limited number of studies. A recent large study using a national
      histopathological database, and our study based on the stage of H. pylori-related
      chronic gastritis as determined by serum levels of H. pylori antibody titer and
      pepsinogen, indicated that H. pylori-related CAG confers an increased risk of
      colorectal neoplasm, and more extensive atrophic gastritis will probably be
      associated with even higher risk of neoplasm. In addition, our study suggested
      that the activity of H. pylori-related chronic gastritis is correlated with
      colorectal neoplasm risk. H. pylori-related chronic gastritis could be involved
      in an increased risk of colorectal neoplasm that appears to be enhanced by the
      progression of gastric atrophy and the presence of active inflammation. 

PMID- 24587621
TI  - Exploring alternative treatments for Helicobacter pylori infection.
AB  - Helicobacter pylori (H. pylori) is a successful pathogen that can persist in the
      stomach of an infected person for their entire life. It provokes chronic gastric
      inflammation that leads to the development of serious gastric diseases such as
      peptic ulcers, gastric cancer and Mucosa associated lymphoid tissue lymphoma. It
      is known that these ailments can be avoided if the infection by the bacteria can
      be prevented or eradicated. Currently, numerous antibiotic-based therapies are
      available. However, these therapies have several inherent problems, including the
      appearance of resistance to the antibiotics used and associated adverse effects,
      the risk of re-infection and the high cost of antibiotic therapy. The delay in
      developing a vaccine to prevent or eradicate the infection has furthered research
      into new therapeutic approaches. This review summarises the most relevant recent
      studies on vaccine development and new treatments using natural resources such as
      plants, probiotics and nutraceuticals. In addition, novel alternatives based on
      microorganisms, peptides, polysaccharides, and intragastric violet light
      irradiation are presented. Alternative therapies have not been effective in
      eradicating the bacteria but have been shown to maintain low bacterial levels.
      Nevertheless, some of them are useful in preventing the adverse effects of
      antibiotics, modulating the immune response, gastroprotection, and the general
      promotion of health. Therefore, those agents can be used as adjuvants of
      allopathic anti-H. pylori eradication therapy. 

PMID- 24587624
TI  - Current progress toward eradicating Helicobacter pylori in East Asian countries:
      differences in the 2013 revised guidelines between China, Japan, and South Korea.
AB  - New 2013 guidelines on Helicobacter pylori (H. pylori) infection have been
      published in China, Japan, and South Korea. Like the previous ones, these new
      guidelines differ between the three countries with regard to the indications for
      H. pylori eradication, diagnostic methods, and treatment regimens. The most
      profound change among all of the guidelines is that the Japanese national health
      insurance system now covers the expenses for all infected subjects up to second
      line treatment. This makes the Japanese indications for eradication much wider
      than those in China and South Korea. With regard to the diagnosis, a serum H.
      pylori antibody test is not recommended in China, whereas it is considered to be
      the most reliable method in Japan. A decrease relative to the initial antibody
      titer of more than 50% after 6-12 mo is considered to be the most accurate method
      for determining successful eradication in Japan. In contrast, only the urea
      breath test is recommended after eradication in China, while either noninvasive
      or invasive methods (except the bacterial culture) are recommended in South
      Korea. Due to the increased rate of antibiotics resistance, first-line treatment
      is omitted in China and South Korea in cases of clarithromycin resistance.
      Notably, the Japanese regimen consists of a lower dose of antibiotics for a
      shorter duration (7 d) than in the other countries. There is neither 14 d nor
      bismuth-based regimen in the first-line and second-line treatment in Japan. Such
      differences among countries might be due to differences in the approvals granted
      by the governments and national health insurance system in each country. Further
      studies are required to achieve the best results in the diagnosis and treatment
      of H. pylori infection based on cost-effectiveness in East Asian countries. 

PMID- 24587625
TI  - Helicobacter pylori and gastric cancer: Indian enigma.
AB  - Helicobacter pylori (H. pylori) is a gram negative microaerophilic bacterium
      which resides in the mucous linings of the stomach. It has been implicated in the
      causation of various gastric disorders including gastric cancer. The geographical
      distribution and etiology of gastric cancer differ widely in different
      geographical regions and H. pylori, despite being labeled as a grade I
      carcinogen, has not been found to be associated with gastric cancer in many
      areas. Studies in Asian countries such as Thailand, India, Bangladesh, Pakistan,
      Iran, Saudi Arabian countries, Israel and Malaysia, have reported a high
      frequency of H. pylori infection co-existing with a low incidence of gastric
      cancer. In India, a difference in the prevalence of H. pylori infection and
      gastric cancer has been noted even in different regions of the country leading to
      a puzzle when attempting to find the causes of these variations. This puzzle of
      H. pylori distribution and gastric cancer epidemiology is known as the Indian
      enigma. In this review we have attempted to explain the Indian enigma using
      evidence from various Indian studies and from around the globe. This review
      covers aspects of epidemiology, the various biological strains present in
      different parts of the country and within individuals, the status of different H.
      pylori-related diseases and the molecular pathogenesis of the bacterium. 

PMID- 24587622
TI  - An association between Helicobacter pylori and upper respiratory tract disease:
      fact or fiction?
AB  - Helicobacter pylori (H. pylori) is a major cause of chronic gastritis and gastric
      ulcers and considerable evidence supports the notion that infection with this
      bacterium is also associated with gastric malignancy in addition to various other
      conditions including pulmonary, vascular and autoimmune disorders. Gastric juice
      infected with H. pylori might play an important role in upper respiratory tract
      infection. Although direct and/or indirect mechanisms might be involved in the
      association between H. pylori and upper respiratory tract diseases, the
      etiological role of H. pylori in upper respiratory tract disorders has not yet
      been fully elucidated. Although various studies over the past two decades have
      suggested a relationship between H. pylori and upper respiratory tract diseases,
      the findings are inconsistent. The present overview describes the outcomes of
      recent investigations into the impact of H. pylori on upper respiratory tract and
      adjacent lesions. 

PMID- 24587626
TI  - Helicobacter pylori and skin autoimmune diseases.
AB  - Autoimmune skin diseases are characterized by dysregulation of the immune system
      resulting in a loss of tolerance to skin self-antigen(s). The prolonged
      interaction between the bacterium and host immune mechanisms makes Helicobacter
      pylori (H. pylori) a plausible infectious agent for triggering autoimmunity.
      Epidemiological and experimental data now point to a strong relation of H. pylori
      infection on the development of many extragastric diseases, including several
      allergic and autoimmune diseases. H. pylori antigens activate cross-reactive T
      cells and induce autoantibodies production. Microbial heat shock proteins (HSP)
      play an important role of in the pathogenesis of autoimmune diseases because of
      the high level of sequence homology with human HSP. Eradication of H. pylori
      infection has been shown to be effective in some patients with chronic autoimmune
      urticaria, psoriasis, alopecia areata and Schoenlein-Henoch purpura. There is
      conflicting and controversial data regarding the association of H. pylori
      infection with Behcet's disease, scleroderma and autoimmune bullous diseases. No
      data are available evaluating the association of H. pylori infection with other
      skin autoimmune diseases, such as vitiligo, cutaneous lupus erythematosus and
      dermatomyositis. The epidemiological and experimental evidence for a possible
      role of H. pylori infection in skin autoimmune diseases are the subject of this
      review. 

PMID- 24587627
TI  - Second and third line treatment options for Helicobacter pylori eradication.
AB  - Helicobacter pylori is a highly successful bacterium with a high global
      prevalence and the infection carries significant disease burden. It is also
      becoming increasingly difficult to eradicate and the main reason for this is
      growing primary antibiotic resistance rates in a world where antibiotics are
      frequently prescribed and readily available. Despite knowing much more about the
      bacterium since its discovery, such as its genomic makeup and pathogenesis, we
      have seen declining treatment success. Therefore, clinicians today must be
      prepared to face one, two or even multiple treatment failures, and should be
      equipped with sufficient knowledge to decide on the appropriate salvage therapy
      when this happens. This article discusses the factors contributing to treatment
      failure and reviews the second and third-line treatment strategies that have been
      investigated. Established empiric second line treatment options include both
      bismuth based quadruple therapy and levofloxacin based triple therapy. Antibiotic
      testing is recommended prior to initiating third line treatment. In the event
      that antibiotic susceptibility testing is unavailable, third line treatment
      options include rifabutin, rifaximin and sitafloxacin based therapies. 

PMID- 24587628
TI  - Clinical proteomics identifies potential biomarkers in Helicobacter pylori for
      gastrointestinal diseases.
AB  - The development of gastrointestinal diseases has been found to be associated with
      Helicobacter pylori (H. pylori) infection and various biochemical stresses in
      stomach and intestine. These stresses, such as oxidative, osmotic and acid
      stresses, may bring about bi-directional effects on both hosts and H. pylori,
      leading to changes of protein expression in their proteomes. Therefore, proteins
      differentially expressed in H. pylori under various stresses not only reflect
      gastrointestinal environment but also provide useful biomarkers for disease
      diagnosis and prognosis. In this regard, proteomic technology is an ideal tool to
      identify potential biomarkers as it can systematically monitor proteins and
      protein variation on a large scale of cell's translational landscape, permitting
      in-depth analyses of host and pathogen interactions. By performing two
      dimensional polyacrylamide gel electrophoresis (2-DE) followed by liquid
      chromatography-nanoESI-mass spectrometry (nanoLC-MS/MS), we have successfully
      pinpointed alkylhydroperoxide reductase (AhpC), neutrophil-activating protein and
      non-heme iron-binding ferritin as three prospective biomarkers showing up
      regulation in H. pylori under oxidative, osmotic and acid stresses, respectively.
      Further biochemical characterization reveals that various environmental stresses
      can induce protein structure change and functional conversion in the identified
      biomarkers. Especially salient is the antioxidant enzyme AhpC, an abundant
      antioxidant protein present in H. pylori. It switches from a peroxide reductase
      of low-molecular-weight (LMW) oligomers to a molecular chaperone of high
      molecular-weight (HMW) complexes under oxidative stress. Different seropositivy
      responses against LMW or HMW AhpC in H. pylori-infected patients faithfully match
      the disease progression from disease-free healthy persons to patients with
      gastric ulcer and cancer. These results has established AhpC of H. pylori as a
      promising diagnostic marker for gastrointestinal maladies, and highlight the
      utility of clinical proteomics for identifying disease biomarkers that can be
      uniquely applied to disease-oriented translational medicine. 

PMID- 24587629
TI  - Endoscopic papillectomy: indications, techniques, and results.
AB  - Endoscopic papillectomy (EP) is currently accepted as a viable alternative
      therapy to surgery in sporadic ampullary adenoma and has been reported to have
      high success and low recurrence rates. At present, the indications for EP are not
      yet fully established. The accepted criteria for EP include size (up to 5 cm), no
      evidence of intraductal growth, and no evidence of malignancy on endoscopic
      findings (ulceration, friability, and spontaneous bleeding). Endoscopic
      ultrasound (EUS) is the imaging modality of choice for local T staging in
      ampullary neoplasms. Data reported in the literature have revealed that linear
      EUS is superior to helical computed tomography in the preoperative assessment of
      tumor size, detection of regional nodal metastases and detection of major
      vascular invasion. Endoscopic ampullectomy is performed using a standard
      duodenoscope in a similar manner to snare polypectomy of a mucosal lesion. There
      is no standardization of the equipment or technique and broad EP methods are
      described. Endoscopic ampullectomy is considered a ''high-risk'' procedure due to
      complications. Complications of endoscopic papillectomy can be classified as
      early (pancreatitis, bleeding, perforation, and cholangitis) and late (papillary
      stenosis) complications. The appropriate use of stenting after ampullectomy may
      prevent post-procedural pancreatitis and papillary stenosis. Tumor recurrence of
      benign lesions occurs in up to 20% of patients and depends on tumor size, final
      histology, presence of intraductal tumor, coexisting familial adenomatous
      polyposis (FAP), and the expertise of the endoscopist. Recurrent lesions are
      usually benign and most can be retreated endoscopically. 

PMID- 24587630
TI  - Incidence and mortality of primary liver cancer in England and Wales: changing
      patterns and ethnic variations.
AB  - AIM: To explore recent trends, modes of diagnosis, ethnic distribution and the
      mortality to incidence ratio of primary liver cancer by subtypes in England and
      Wales. METHODS: We obtained incidence (1979-2008) and mortality (1968-2008) data
      for primary liver cancer for England and Wales and calculated age-standardised
      incidence and mortality rates. Trends in age-standardised mortality (ASMR) and
      incidence (ASIR) rates and basis of diagnosis of primary liver cancer and
      subcategories: hepatocellular carcinoma, intrahepatic bile duct and unspecified
      liver tumours, were analysed over the study period. Changes in guidelines for the
      diagnosis of primary liver cancer (PLC) may impact changing trends in the rates
      that may be obtained. We thus explored changes in the mode of diagnosis as
      reported to cancer registries. Furthermore, we examined the distribution of these
      tumours by ethnicity. Most of the statistical manipulations of these data was
      carried out in Microsoft excel(r) (Seattle, Washington, United Sttaes).
      Additional epidemiological statistics were done in Epi Info software (Atlanta,
      GA, United Sttaes). To define patterns of change over time, we evaluated trends
      in ASMR and ASIR of PLC and intrahepatic bile duct carcinoma (IHBD) using a least
      squares regression line fitted to the natural logarithm of the mortality and
      incidence rates. We estimated the patterns of survival over subsequent 5 and 10
      years using complement of mortality to incidence ratio (1-MIR). RESULTS: Age
      standardised mortality rate of primary liver cancer increased in both sexes: from
      2.56 and 1.29/100000 in 1968 to 5.10 and 2.63/100000 in 2008 for men and women
      respectively. The use of histology for diagnostic confirmation of primary liver
      cancer increased from 35.7% of registered cases in 1993 to plateau at about 50%
      during 2005 to 2008. Reliance on cytology as a basis of diagnosis has maintained
      a downward trend throughout the study period. Although approximately 30% of the
      PLC registrations had information on ethnicity, there was a relatively higher
      registration of the major tumour subtypes in patients whose ethnic backgrounds
      were from high incident regions of the world. Survival from PLC is estimated to
      get poorer in 10 years (2018) relative to 2008, particularly as a result of IHBD.
      CONCLUSION: Incidence and mortality of PLC, and particularly IHBD, have continued
      to rise in England and Wales. Changes in the modes of diagnosis may be
      contributing.

PMID- 24587631
TI  - Regulation of hepatic EAAT-2 glutamate transporter expression in human liver
      cholestasis.
AB  - AIM: To investigate the activity and expression of EAAT2 glutamate transporter in
      both in vitro and in vivo models of cholestasis. METHODS: This study was
      conducted on human hepatoblastoma HepG2 cell cultures, the liver of bile duct
      ligated rats and human specimens from cholestatic patients. EAAT2 glutamate
      transporter activity and expression were analyzed using a substrate uptake assay,
      immunofluorescence, reverse transcription-polymerase chain reaction, and
      immunohistochemistry, respectively. RESULTS: In HepG2 cells, cholestasis was
      mimicked by treating cells with the protein kinase C activator, phorbol 12
      myristate 13-acetate. Under such conditions, EAAT2 transporter activity was
      decreased both at the level of substrate affinity and maximal transport velocity.
      The decreased uptake was correlated with intracellular translocation of EAAT2
      molecules as demonstrated using immunofluorescence. In the liver of bile duct
      ligated rats, an increase in EAAT2 transporter protein expression in hepatocytes
      was demonstrated using immunohistochemistry. The same findings were observed in
      human liver specimens of cholestasis in which high levels of gamma-glutamyl
      transpeptidase were documented in patients with biliary atresia and progressive
      familial intrahepatic cholestasis type 3. CONCLUSION: This study demonstrates the
      alteration in glutamate handling by hepatocytes in liver cholestasis and suggests
      a potential cross-talk between glutamatergic and bile systems.

PMID- 24587632
TI  - Prognostic value of chemotherapy-induced hematological toxicity in metastatic
      colorectal cancer patients.
AB  - AIM: To establish whether chemotherapy-induced neutropenia is predictive of
      better outcome in patients with metastatic colorectal cancer (mCRC). METHODS:
      Survival and patient characteristics from consecutive mCRC patients treated in
      the Centre Georges Francois Leclerc, Dijon, France between January 2001 and
      December 2011 were analyzed. Patient and tumor characteristics, hematological
      toxicity (neutropenia, anemia, and thrombocytopenia), and type of chemotherapy
      received were recorded. RESULTS: We retrospectively analyzed data from 399
      consecutive patients with mCRC who received at least one line of chemotherapy.
      Median follow up was 6.3 years. Eighty-eight percent of the patients received
      more than two lines of chemotherapy. By univariate analysis, whatever their
      grade, neutropenia and thrombocytopenia occurring during the first two lines of
      chemotherapy were significantly associated with better overall survival (HR =
      0.55, 95%CI: 0.43-0.70, P < 0.0001 and HR = 0.70, 95%CI: 0.56-0.88, P = 0.025
      respectively). In contrast, anemia during chemotherapy was significantly
      associated with poorer overall survival (HR = 1.9, 95%CI: 1.22-2.97, P = 0.005).
      Multivariate analysis revealed that both neutropenia and thrombocytopenia were
      significantly associated with better overall survival: HR = 0.43, 95%CI: 0.29
      0.64, P < 0.0001 and HR = 0.69, 95%CI: 0.49-0.98, P = 0.036, respectively.
      CONCLUSION: These data suggest that occurrence of neutropenia or thrombocytopenia
      during first- or second-line chemotherapy for mCRC is associated with better
      survival.

PMID- 24587634
TI  - Is the severity of gastroesophageal reflux dependent on hiatus hernia size?
AB  - AIM: To determine if the severity of gastroesophageal reflux disease is dependent
      on the size of a hiatus hernia. METHODS: Seventy-five patients with either a
      small (n = 25), medium (n = 25) or large (n = 25) hiatus hernia (assessed by high
      resolution esophageal manometry) were investigated using 24-h esophageal
      monitoring and a self-assessed symptom questionnaire. The questionnaire comprised
      the following items, each graded from 0 to 3 according to severity: heartburn;
      pharyngeal burning sensation; acid regurgitation; and chest pain. RESULTS: The
      percentage total reflux time was significantly longer in the group with hernia of
      5 cm or more compared with the group with a hernia of < 3 cm (P < 0.002), and the
      group with a hernia of 3 to < 5 cm (P < 0.04). Pharyngeal burning sensation,
      heartburn and acid regurgitation were more common with large hernias than small
      hernias, but the frequency of chest pain was similar in all three hernia groups.
      CONCLUSION: Patients with a large hiatus hernia are more prone to have
      pathological gastroesophageal reflux and to have more acid symptoms than patients
      with a small hiatus hernia. However, it is unlikely that patients with an absence
      of acid symptoms will have pathological reflux regardless of hernia size.

PMID- 24587633
TI  - Does training and experience influence the accuracy of computed tomography
      colonography interpretation?
AB  - AIM: To evaluate the effect of experience on the accuracy rate of computed
      tomography colonography (CTC) interpretation and patient preferences/satisfaction
      for CTC and colonoscopy. METHODS: A prospective, non-randomized, observational
      study performed in a single, tertiary care center involving 90 adults who
      underwent CTC followed by colonoscopy on the same day. CTC was interpreted by an
      abdominal imaging radiologist and then a colonoscopy was performed utilizing
      segmental un-blinding and re-examination as required. A radiology resident and
      two gastroenterology (GI) fellows blinded to the results also interpreted the CTC
      datasets independently. Accuracy rates and trend changes were determined for each
      reader to assess for a learning curve. RESULTS: Among 90 patients (57% male) aged
      55 +/- 8.9 years, 39 polyps >= 6 mm were detected in 20 patients and 13 polyps >
      9 mm in 10 patients. Accuracy rates were 88.9% (>= 6 mm) and 93.3% (> 9 mm) for
      the GI Radiologist, 89.8% (>= 6 mm) and 98.9% (> 9 mm) for the Radiology Resident
      and 86.7% and 95.6% (>= 6 mm) and 87.8% and 94.4% (> 9 mm) for each of the GI
      fellows respectively. The reader's accuracy rate did not change significantly
      with the percentage change rate ranging between -1.7 to 0.9 (P = 0.12 to 0.56).
      Patients considered colonoscopy more satisfactory than CTC (30% vs 4%, P <
      0.0001), they felt less anxiety during colonoscopy (36% vs 7%, P < 0.0001), they
      experienced less pain or discomfort during colonoscopy compared to CTC (69% vs
      4%, P < 0.0001) and colonoscopy was preferred by 77% of the participants as a
      repeat screening test for the future. CONCLUSION: No statistically significant
      learning curve was identified in CTC interpretation suggesting that further study
      is required to identify the necessary training to adequately interpret CTC scans.

PMID- 24587635
TI  - Percutaneous radiofrequency ablation for early hepatocellular carcinoma: risk
      factors for survival.
AB  - AIM: To evaluate outcomes of radiofrequency ablation (RFA) therapy for early
      hepatocellular carcinoma (HCC) and identify survival- and recurrence-related
      factors. METHODS: Consecutive patients diagnosed with early HCC by computed
      tomography (CT) or magnetic resonance imaging (MRI) (single nodule of <= 5 cm, or
      multi- (up to 3) nodules of <= 3 cm each) and who underwent RFA treatment with
      curative intent between January 2010 and August 2011 at the Instituto do Cancer
      do Estado de Sao Paulo, Brazil were enrolled in the study. RFA of the liver
      tumors (with 1.0 cm ablative margin) was carried out under CT-fluoro scan and
      ultrasonic image guidance of the percutaneous ablation probes. Procedure-related
      complications were recorded. At 1-mo post-RFA and 3-mo intervals thereafter, CT
      and MRI were performed to assess outcomes of complete response (absence of
      enhancing tissue at the tumor site) or incomplete response (enhancing tissue
      remaining at the tumor site). Overall survival and disease-free survival rates
      were estimated by the Kaplan-Meier method and compared by the log rank test or
      simple Cox regression. The effect of risk factors on survival was assessed by the
      Cox proportional hazard model. RESULTS: A total of 38 RFA sessions were performed
      during the study period on 34 patients (age in years: mean, 63 and range, 49-84).
      The mean follow-up time was 22 mo (range, 1-33). The study population showed
      predominance of male sex (76%), less severe liver disease (Child-Pugh A, n = 26;
      Child-Pugh B, n = 8), and single tumor (65%). The maximum tumor diameters ranged
      from 10 to 50 mm (median, 26 mm). The initial (immediately post-procedure) rate
      of RFA-induced complete tumor necrosis was 90%. The probability of achieving
      complete response was significantly greater in patients with a single nodule (vs
      patients with multi-nodules, P = 0.04). Two patients experienced major
      complications, including acute pulmonary edema (resolved with intervention) and
      intestinal perforation (led to death). The 1- and 2-year overall survival rates
      were 82% and 71%, respectively. Sex, tumor size, initial response, and recurrence
      status influenced survival, but did not reach the threshold of statistical
      significance. Child-Pugh class and the model for end-stage liver disease score
      were identified as predictors of survival by simple Cox regression, but only
      Child-Pugh class showed a statistically significant association to survival in
      multiple Cox regression analysis (HR = 15; 95%CI: 3-76 mo; P = 0.001). The 1- and
      2-year cumulative disease-free survival rates were 65% and 36%, respectively.
      CONCLUSION: RFA is an effective therapy for local tumor control of early HCC, and
      patients with preserved liver function are the best candidates.

PMID- 24587636
TI  - Recombinant streptokinase vs phenylephrine-based suppositories in acute
      hemorrhoids, randomized, controlled trial (THERESA-3).
AB  - AIM: To compare the efficacy and safety of recombinant streptokinase (rSK) and
      phenylephrine-based suppositories in acute hemorrhoidal disease. METHODS: A
      multicenter (14 sites), randomized (1:1), open, parallel groups, active
      controlled trial was done. After inclusion, subjects with acute symptoms of
      hemorrhoids, who gave their written, informed consent to participate, were
      centrally randomized to receive, as outpatients, rSK (200000 IU) or 0.25%
      phenylephrine suppositories, which had different organoleptic characteristics.
      Treatment was administered by the rectal route, one unit every 6 h during 48 h
      for rSK, and up to a maximum of 5 d (20 suppositories) for phenylephrine.
      Evaluations were performed at 3, 5 and 10 d post-inclusion. The main end-point
      was the 5(th)-day complete clinical response (disappearance of pain and edema,
      and >= 70% reduction of the lesion size). Time to response and need for
      thrombectomy were secondary efficacy variables. Adverse events were evaluated
      too. RESULTS: 5(th) day complete response rates were 83/110 (75.5%) and 36/110
      (32.7%) with rSK and phenylephrine suppositories, respectively. This 42.7%
      difference (95%CI: 30.5-54.2) was highly significant (P < 0.001). The advantage
      was detected since the early 3(rd) day evaluation (37.3% vs 6.4% for the rSK and
      active control groups, respectively; P < 0.001) and was kept even at the late
      10(th) day assessment (83.6% vs 58.2% for rSK and phenylephrine, respectively; P
      < 0.001). Time for complete response was significantly shorter (P = 0.031; log
      rank test) in the rSK group (median: 4.9 d; 95%CI: 4.8-5.0) with respect to the
      active control (median: 9.8 d; 95%CI: 9.8-10.0). Thrombectomy was necessary in
      1/59 and 8/57 patients with baseline thrombosis in the rSK and phenylephrine
      groups, respectively (P = 0.016). There were no adverse events attributable to
      the experimental treatment. CONCLUSION: rSK suppositories showed a significant
      advantage over a widely used over-the-counter phenylephrine preparation for the
      treatment of acute hemorrhoidal illness, with an adequate safety profile.

PMID- 24587637
TI  - Transjugular intrahepatic portosystemic shunt with covered stents for
      hepatocellular carcinoma with portal vein tumor thrombosis.
AB  - AIM: To evaluate transjugular intrahepatic portosystemic shunt (TIPS) with
      covered stents for hepatocellular carcinoma (HCC) with main portal vein tumor
      thrombus (PVTT). METHODS: Eleven advanced HCC patients (all male, aged 37-78
      years, mean: 54.3 +/- 12.7 years) presented with acute massive upper
      gastrointestinal bleeding (n = 9) or refractory ascites (n = 2) due to tumor
      thrombus in the main portal vein. The diagnosis of PVTT was based on contrast
      enhanced computed tomography and color Doppler sonography. The patients underwent
      TIPS with covered stents. Clinical characteristics and average survival time of
      11 patients were analyzed. Portal vein pressure was assessed before and after
      TIPS. The follow-up period was 2-18 mo. RESULTS: TIPS with covered stents was
      successfully completed in all 11 patients. The mean portal vein pressure was
      reduced from 32.0 to 11.8 mmHg (t = 10.756, P = 0.000). Gastrointestinal bleeding
      was stopped in nine patients. Refractory ascites completely disappeared in one
      patient and was alleviated in another. Hepatic encephalopathy was observed in six
      patients and was resolved with drug therapy. During the follow-up, ultrasound
      indicated the patency of the shunt and there was no recurrence of symptoms. Death
      occurred 2-14 mo (mean: 5.67 mo) after TIPS in nine cases, which were all due to
      multiple organ failure. In the remaining two cases, the patients were still alive
      at the 16- and 18-mo follow-up, respectively. CONCLUSION: TIPS with covered
      stents for HCC patients with tumor thrombus in the main portal vein is
      technically feasible, and short-term efficacy is favorable.

PMID- 24587638
TI  - Possible roles of insulin, IGF-1 and IGFBPs in initiation and progression of
      colorectal cancer.
AB  - AIM: To investigate the roles of serum insulin, insulin-like growth factor-1 (IGF
      1), and insulin-like growth factor binding proteins (IGFBPs) in the initiation
      and progression of colorectal cancer. METHODS: We determined serum insulin, IGF-1
      and IGFBPs levels in 615 colorectal cancer patients and 650 control healthy
      donors by enzyme-linked immunosorbent assay (ELISA). In the meantime, their body
      mass index (BMI) and waist-to-hip ratio (WHR) were measured. RESULTS: Serum
      levels of insulin and IGF-1 as well as IGF-1/IGFBP-3 ratio in pre-operation
      patients were significantly elevated, but the level of IGFBP-3 was significantly
      decreased compared with normal controls and post-operation patients (P < 0.05 and
      P < 0.001, respectively). There is no significant difference (P > 0.05) in the
      levels of insulin, IGF-1, IGFBP-1, IGFBP-3 and IGF-1/IGFBP-3 between the patients
      with and without hepatic as well as distal abdominal metastases. WHR and BMI of
      colon cancer patients were positively and significantly correlated with the
      levels of insulin and IGF-1/IGFBP-3. In contrast, WHR and BMI were negatively
      correlated with IGFBP-3 level. CONCLUSION: The elevation of insulin, IGF-1 as
      well as IGF-1/IGFBP-3 ratio and the reduction of IGFBP-3 may be related to the
      initiation of colorectal cancer, but they are not related to the progression and
      outcome of the disease.

PMID- 24587640
TI  - An effective and safe gastric endoscopic submucosal dissection in the right
      lateral position using an inverted overtube.
AB  - Previously, we reported the efficacy of a newly developed inverted overtube in
      shortening the hemostatic time and obtaining a clear endoscopic view in emergency
      endoscopic hemostasis. This device also helped us to perform gastric endoscopic
      submucosal dissection (ESD) more safely by changing the direction of gravity in
      the right lateral position. To perform a safe ESD, it is important to make an
      appropriate angle and distance between the electric knife and the gastric mucosa.
      In this position, the distance to gastric mucosa is reduced, and the angle of the
      electric knife changes from vertical to somewhat oblique, facilitating safer
      cutting. 

PMID- 24587639
TI  - Protective role of hydrogen-rich water on aspirin-induced gastric mucosal damage
      in rats.
AB  - AIM: To investigate the role of the hydrogen-rich water (HRW) in the prevention
      of aspirin-induced gastric mucosal injury in rats. METHODS: Forty male rats were
      allocated into four groups: normal control group, HRW group, aspirin group, and
      HRW plus aspirin group. The protective efficacy was tested by determining the
      gastric mucosal damage score. Malondialdehyde (MDA), superoxide dismutase (SOD),
      myeloperoxidase (MPO), interleukin (IL)-06 and tumor necrosis factor (TNF)-alpha
      in gastric tissues were evaluated. The serum levels of IL-1beta and TNF-alpha
      were also detected. Histopathology of gastric tissues and localization of
      Cyclooxygenase 2 (COX-2) were detected using hematoxylin and eosin staining and
      immunohistochemistry, respectively. RESULTS: Pretreatment with HRW obviously
      reduced aspirin-induced gastric damage scores (4.04 +/- 0.492 vs 2.10 +/- 0.437,
      P < 0.05). The oxidative stress levels of MDA and MPO in the gastric tissues
      increased significantly in the aspirin-treated group compared with the HRW group
      (2.43 +/- 0.145 vs 1.79 +/- 0.116 nmol/mg prot, P < 0.05 and 2.53 +/- 0.238 vs
      1.40 +/- 0.208 U/g tissue, P < 0.05, respectively). HRW could obviously elevated
      the SOD levels in the gastric tissues (37.94 +/- 8.44 vs 59.55 +/- 9.02 nmol/mg
      prot, P < 0.05). Pretreatment with HRW significantly reduced IL-06 and TNF-alpha
      in the gastric tissues (46.65 +/- 5.50 vs 32.15 +/- 4.83 pg/mg, P < 0.05 and
      1305.08 +/- 101.23 vs 855.96 +/- 93.22 pg/mg, P < 0.05), and IL-1beta and TNF
      alpha in the serum (505.38 +/- 32.97 vs 343.37 +/- 25.09 pg/mL, P < 0.05 and
      264.53 +/- 28.63 vs 114.96 +/- 21.79 pg/mL, P < 0.05) compared to treatment with
      aspirin alone. HRW could significantly decrease the COX-2 expression in the
      gastric tissues (staining score: 8.4 +/- 2.1 vs 2.9 +/- 1.5, P < 0.05).
      CONCLUSION: HRW pretreatment alleviated the aspirin-induced gastric lesions by
      inhibiting the oxidative stress, inflammatory reaction and reducing the COX-2 in
      the gastric tissues.

PMID- 24587641
TI  - Peritonitis with small bowel perforation caused by a fish bone in a healthy
      patient.
AB  - Perforation of the gastrointestinal tract by ingested foreign bodies is extremely
      rare in otherwise healthy patients, accounting for < 1% of cases. Accidentally
      ingested foreign bodies could cause small bowel perforation through a hernia sac,
      Meckel's diverticulum, or the appendix, all of which are uncommon. Despite their
      sharp ends and elongated shape, bowel perforation caused by ingested fish bones
      is rarely reported, particularly in patients without intestinal disease. We
      report a case of 57-year-old female who visited the emergency room with
      periumbilical pain and no history of underlying intestinal disease or intra
      abdominal surgery. Abdominal computed tomography and exploratory laparotomy
      revealed a small bowel micro-perforation with a 2.7-cm fish bone penetrating the
      jejunal wall. 

PMID- 24587642
TI  - Characterization of primary hepatic carcinosarcoma by contrast-enhanced
      ultrasonography: a case report.
AB  - Primary hepatic carcinosarcoma is a rare tumor and is comprised of a mixture of
      carcinomatous and sarcomatous elements. We present a case of primary
      carcinosarcoma of the liver in a 59-year-old woman, which was confirmed by
      pathology following surgical resection. Using contrast-enhanced ultrasonography,
      the tumor showed peripheral nodular hyperenhancement in the arterial phase with
      two feeding arterial vessels and a large internal non-enhancing portion in the
      center. The peripheral nodular portion of the tumor showed hypoenhancement in the
      later phase. 

PMID- 24587644
TI  - Role of imaging in predicting response to neoadjuvant chemotherapy in gastric
      cancer.
AB  - With the proven overall benefit of neoadjuvant chemotherapy in patients with
      locally advanced gastric cancer, there has come a need to discriminate responders
      from non-responders. In this article, the current role of anatomical and
      molecular imaging in the prediction of response to neoadjuvant therapy in gastric
      cancer is outlined and future prospects are discussed. 

PMID- 24587643
TI  - Treatment of gastric cancer.
AB  - The authors focused on the current surgical treatment of resectable gastric
      cancer, and significance of peri- and post-operative chemo or chemoradiation.
      Gastric cancer is the 4(th) most commonly diagnosed cancer and the second leading
      cause of cancer death worldwide. Surgery remains the only curative therapy, while
      perioperative and adjuvant chemotherapy, as well as chemoradiation, can improve
      outcome of resectable gastric cancer with extended lymph node dissection. More
      than half of radically resected gastric cancer patients relapse locally or with
      distant metastases, or receive the diagnosis of gastric cancer when tumor is
      disseminated; therefore, median survival rarely exceeds 12 mo, and 5-years
      survival is less than 10%. Cisplatin and fluoropyrimidine-based chemotherapy,
      with addition of trastuzumab in human epidermal growth factor receptor 2 positive
      patients, is the widely used treatment in stage IV patients fit for chemotherapy.
      Recent evidence supports the use of second-line chemotherapy after progression in
      patients with good performance status. 

PMID- 24587645
TI  - Immunotherapy in gastric cancer.
AB  - Gastric cancer is the second most common of cancer-related deaths worldwide. In
      the majority of cases gastric cancer is advanced at diagnosis and although
      medical and surgical treatments have improved, survival rates remain poor. Cancer
      immunotherapy has emerged as a powerful and promising clinical approach for
      treatment of cancer and has shown major success in breast cancer, prostate cancer
      and melanoma. Here, we provide an overview of concepts of modern cancer
      immunotherapy including the theory, current approaches, remaining hurdles to be
      overcome, and the future prospect of cancer immunotherapy in the treatment of
      gastric cancer. Adaptive cell therapies, cancer vaccines, gene therapies,
      monoclonal antibody therapies have all been used with some initial successes in
      gastric cancer. However, to date the results in gastric cancer have been
      disappointing as current approaches often do not stimulate immunity efficiently
      allowing tumors continue to grow despite the presence of a measurable immune
      response. Here, we discuss the identification of targets for immunotherapy and
      the role of biomarkers in prospectively identifying appropriate subjects or
      immunotherapy. We also discuss the molecular mechanisms by which tumor cells
      escape host immunosurveillance and produce an immunosuppressive tumor
      microenvironment. We show how advances have provided tools for overcoming the
      mechanisms of immunosuppression including the use of monoclonal antibodies to
      block negative regulators normally expressed on the surface of T cells which
      limit activation and proliferation of cytotoxic T cells. Immunotherapy has
      greatly improved and is becoming an important factor in such fields as medical
      care and welfare for human being. Progress has been rapid ensuring that the
      future of immunotherapy for gastric cancer is bright. 

PMID- 24587646
TI  - Role of the tumor microenvironment in the pathogenesis of gastric carcinoma.
AB  - Gastric carcinoma (GC) is the 4(th) most prevalent cancer and has the 2(nd)
      highest cancer-related mortality rate worldwide. Despite the incidence of GC has
      decreased over the past few decades, it is still a serious health problem.
      Chronic inflammatory status of the stomach, caused by the infection of
      Helicobacter pylori (H. pylori) and through the production of inflammatory
      mediators within the parenchyma is suspected to play an important role in the
      initiation and progression of GC. In this review, the correlation between chronic
      inflammation and H. pylori infection as an important factor for the development
      of GC will be discussed. Major components, including tumor-associated
      macrophages, lymphocytes, cancer-associated fibroblasts, angiogenic factors,
      cytokines, and chemokines of GC microenvironment and their mechanism of action on
      signaling pathways will also be discussed. Increasing our understanding of how
      the components of the tumor microenvironment interact with GC cells and the
      signaling pathways involved could help identify new therapeutic and
      chemopreventive targets.

PMID- 24587648
TI  - Cyr61/CTGF/Nov family proteins in gastric carcinogenesis.
AB  - Gastric cancer (GC) is the second leading cause of cancer-related death. The poor
      survival rate may reflect the relatively aggressive tumor biology of GC.
      Recently, the importance of the tumor microenvironment in carcinogenesis has
      emerged. In the tumor microenvironment, tumor cells and the surrounding stromal
      cells aberrantly secrete matricellular proteins capable of modulating
      carcinogenesis and regulating metastasis. The Cyr61/CTGF/Nov (CCN) proteins are a
      family of matricellular proteins with variable roles in many physiological and
      pathological processes. The evidence suggests that CCN family proteins contribute
      to GC carcinogenic processes. Here, we briefly review recent research on the
      effects of CCN family proteins in GC carcinogenesis and the development of new
      targeted agents in this field. 

PMID- 24587647
TI  - CXC chemokines and chemokine receptors in gastric cancer: from basic findings
      towards therapeutic targeting.
AB  - Gastric cancer is the fourth most common cancer, and the second-highest cause of
      cancer-related deaths worldwide. Despite extensive research to identify novel
      diagnostic and therapeutic agents, patients with advanced gastric cancer suffer
      from a poor quality of life and poor prognosis, and treatment is dependent mainly
      on conventional cytotoxic chemotherapy. To improve the quality of life and
      survival of gastric cancer patients, a better understanding of the underlying
      molecular pathologies, and their application towards the development of novel
      targeted therapies, is urgently needed. Chemokines are a group of small proteins
      associated with cytoskeletal rearrangements, the directional migration of several
      cell types during development and physiology, and the host immune response via
      interactions with G-protein coupled receptors. There is also growing evidence to
      suggest that chemokines not only play a role in the immune system, but are also
      involved in the development and progression of tumors. In gastric cancer, CXC
      chemokines and chemokine receptors regulate the trafficking of cells in and out
      of the tumor microenvironment. CXC chemokines and their receptors can also
      directly influence tumorigenesis by modulating tumor transformation, survival,
      growth, invasion and metastasis, as well as indirectly by regulating
      angiogenesis, and tumor-leukocyte interactions. In this review, we will focus on
      the roles of CXC chemokines and their receptors in the development, progression,
      and metastasis of gastric tumors, and discuss their therapeutic potential for
      gastric cancer. 

PMID- 24587649
TI  - Diabetes and gastric cancer: the potential links.
AB  - This article reviews the epidemiological evidence linking diabetes and gastric
      cancer and discusses some of the potential mechanisms, confounders and biases in
      the evaluation of such an association. Findings from four meta-analyses published
      from 2011 to 2013 suggest a positive link, which may be more remarkable in
      females and in the Asian populations. Putative mechanisms may involve shared risk
      factors, hyperglycemia, Helicobacter pylori (H. pylori) infection, high salt
      intake, medications and comorbidities. Diabetes may increase the risk of gastric
      cancer through shared risk factors including obesity, insulin resistance,
      hyperinsulinemia and smoking. Hyperglycemia, even before the clinical diagnosis
      of diabetes, may predict gastric cancer in some epidemiological studies, which is
      supported by in vitro, and in vivo studies. Patients with diabetes may also have
      a higher risk of gastric cancer through the higher infection rate, lower
      eradication rate and higher reinfection rate of H. pylori. High salt intake can
      act synergistically with H. pylori infection in the induction of gastric cancer.
      Whether a higher risk of gastric cancer in patients with diabetes may be ascribed
      to a higher intake of salt due to the loss of taste sensation awaits further
      investigation. The use of medications such as insulin, metformin, sulfonylureas,
      aspirin, statins and antibiotics may also influence the risk of gastric cancer,
      but most of them have not been extensively studied. Comorbidities may affect the
      development of gastric cancer through the use of medications and changes in
      lifestyle, dietary intake, and the metabolism of drugs. Finally, a potential
      detection bias related to gastrointestinal symptoms more commonly seen in
      patients with diabetes and with multiple comorbidities should be pointed out.
      Taking into account the inconsistent findings and the potential confounders and
      detection bias in previous epidemiological studies, it is expected that there are
      still more to be explored for the clarification of the association between
      diabetes and gastric cancer. 

PMID- 24587650
TI  - Clinical approaches to non-alcoholic fatty liver disease.
AB  - Non-alcoholic fatty liver disease (NAFLD) ranges from simple steatosis to
      nonalcoholic steatohepatitis (NASH), leading to fibrosis and potentially
      cirrhosis, and it is one of the most common causes of liver disease worldwide.
      NAFLD is associated with other medical conditions such as metabolic syndrome,
      obesity, cardiovascular disease and diabetes. NASH can only be diagnosed through
      liver biopsy, but noninvasive techniques have been developed to identify patients
      who are most likely to have NASH or fibrosis, reducing the need for liver biopsy
      and risk to patients. Disease progression varies between individuals and is
      linked to a number of risk factors. Mechanisms involved in the pathogenesis are
      associated with diet and lifestyle, influx of free fatty acids to the liver from
      adipose tissue due to insulin resistance, hepatic oxidative stress, cytokines
      production, reduced very low-density lipoprotein secretion and intestinal
      microbiome. Weight loss through improved diet and increased physical activity has
      been the cornerstone therapy of NAFLD. Recent therapies such as pioglitazone and
      vitamin E have been shown to be beneficial. Omega 3 polyunsaturated fatty acids
      and statins may offer additional benefits. Bariatric surgery should be considered
      in morbidly obese patients. More research is needed to assess the impact of these
      treatments on a long-term basis. The objective of this article is to briefly
      review the diagnosis, management and treatment of this disease in order to aid
      clinicians in managing these patients. 

PMID- 24587652
TI  - Modulation of hepatic steatosis by dietary fatty acids.
AB  - Non-alcoholic fatty liver disease (NAFLD) describes a range of conditions caused
      by fat deposition within liver cells. Liver fat content reflects the equilibrium
      between several metabolic pathways involved in triglyceride synthesis and
      disposal, such as lipolysis in adipose tissue and de novo lipogenesis,
      triglyceride esterification, fatty acid oxidation and very-low-density
      lipoprotein synthesis/secretion in hepatic tissue. In particular, it has been
      demonstrated that hepatic de novo lipogenesis plays a significant role in NAFLD
      pathogenesis. It is widely known that the fatty acid composition of the diet
      influences hepatic lipogenesis along with other metabolic pathways. Therefore,
      dietary fat may not only be involved in the pathogenesis of hepatic steatosis,
      but may also prevent and/or reverse hepatic fat accumulation. In this review,
      major data from the literature about the role of some dietary fats as a potential
      cause of hepatic fat accumulation or as a potential treatment for NAFLD are
      described. Moreover, biochemical mechanisms responsible for an increase or
      decrease in hepatic lipid content are critically analyzed. It is noteworthy that
      both quantitative and qualitative aspects of dietary fat influence triglyceride
      deposition in the liver. A high-fat diet or the dietary administration of
      conjugated linoleic acids induced hepatic steatosis. In contrast, supplementation
      of the diet with krill oil or pine nut oil helped in the prevention and/or in the
      treatment of steatotic liver. Quite interesting is the "case" of olive oil, since
      several studies have often provided different and/or conflicting results in
      animal models.

PMID- 24587651
TI  - Risk of cardiovascular, cardiac and arrhythmic complications in patients with non
      alcoholic fatty liver disease.
AB  - Non-alcoholic fatty liver disease (NAFLD) has emerged as a public health problem
      of epidemic proportions worldwide. Accumulating clinical and epidemiological
      evidence indicates that NAFLD is not only associated with liver-related morbidity
      and mortality but also with an increased risk of coronary heart disease (CHD),
      abnormalities of cardiac function and structure (e.g., left ventricular
      dysfunction and hypertrophy, and heart failure), valvular heart disease (e.g.,
      aortic valve sclerosis) and arrhythmias (e.g., atrial fibrillation). Experimental
      evidence suggests that NAFLD itself, especially in its more severe forms,
      exacerbates systemic/hepatic insulin resistance, causes atherogenic dyslipidemia,
      and releases a variety of pro-inflammatory, pro-coagulant and pro-fibrogenic
      mediators that may play important roles in the pathophysiology of cardiac and
      arrhythmic complications. Collectively, these findings suggest that patients with
      NAFLD may benefit from more intensive surveillance and early treatment
      interventions to decrease the risk for CHD and other cardiac/arrhythmic
      complications. The purpose of this clinical review is to summarize the rapidly
      expanding body of evidence that supports a strong association between NAFLD and
      cardiovascular, cardiac and arrhythmic complications, to briefly examine the
      putative biological mechanisms underlying this association, and to discuss some
      of the current treatment options that may influence both NAFLD and its related
      cardiac and arrhythmic complications. 

PMID- 24587654
TI  - Role of endoplasmic reticulum stress in the pathogenesis of nonalcoholic fatty
      liver disease.
AB  - Nonalcoholic fatty liver disease (NAFLD) has emerged as a common public health
      problem in recent decades. However, the underlying mechanisms leading to the
      development of NAFLD are not fully understood. The endoplasmic reticulum (ER)
      stress response has recently been proposed to play a crucial role in both the
      development of steatosis and progression to nonalcoholic steatohepatitis. ER
      stress is activated to regulate protein synthesis and restore homeostatic
      equilibrium when the cell is stressed due to the accumulation of unfolded or
      misfolded proteins. However, delayed or insufficient responses to ER stress may
      turn physiological mechanisms into pathological consequences, including fat
      accumulation, insulin resistance, inflammation, and apoptosis, all of which play
      important roles in the pathogenesis of NAFLD. Therefore, understanding the role
      of ER stress in the pathogenesis of NAFLD has become a topic of intense
      investigation. This review highlights the recent findings linking ER stress
      signaling pathways to the pathogenesis of NAFLD. 

PMID- 24587653
TI  - Dietary habits and behaviors associated with nonalcoholic fatty liver disease.
AB  - Nonalcoholic fatty liver disease (NAFLD) is one of the most frequent causes of
      health problems in Western (industrialized) countries. Moreover, the incidence of
      infantile NAFLD is increasing, with some of these patients progressing to
      nonalcoholic steatohepatitis. These trends depend on dietary habits and life
      style. In particular, overeating and its associated obesity affect the
      development of NAFLD. Nutritional problems in patients with NAFLD include excess
      intake of energy, carbohydrates, and lipids, and shortages of polyunsaturated
      fatty acids, vitamins, and minerals. Although nutritional therapeutic approaches
      are required for prophylaxis and treatment of NAFLD, continuous nutrition therapy
      is difficult for many patients because of their dietary habits and lifestyle, and
      because the motivation for treatment differs among patients. Thus, it is
      necessary to assess the nutritional background and to identify nutritional
      problems in each patient with NAFLD. When assessing dietary habits, it is
      important to individually evaluate those that are consumed excessively or
      insufficiently, as well as inappropriate eating behaviors. Successful nutrition
      therapy requires patient education, based on assessments of individual nutrients,
      and continuing the treatment. In this article, we update knowledge about NAFLD,
      review the important aspects of nutritional assessment targeting treatment
      success, and present some concrete nutritional care plans which can be applied
      generally. 

PMID- 24587656
TI  - Role of prophylactic antibiotics in cirrhotic patients with variceal bleeding.
AB  - Bacterial infections are common in cirrhotic patients with acute variceal
      bleeding, occurring in 20% within 48 h. Outcomes including early rebleeding and
      failure to control bleeding are strongly associated with bacterial infection.
      However, mortality from variceal bleeding is largely determined by the severity
      of liver disease. Besides a higher Child-Pugh score, patients with hepatocellular
      carcinoma are particularly susceptible to infections. Despite several hypotheses
      that include increased use of instruments, greater risk of aspiration pneumonia
      and higher bacterial translocation, it remains debatable whether variceal
      bleeding results in infection or vice versa but studies suggest that antibiotic
      prophylaxis prior to endoscopy and up to 8 h is useful in reducing bacteremia and
      spontaneous bacterial peritonitis. Aerobic gram negative bacilli of enteric
      origin are most commonly isolated from cultures, but more recently, gram
      positives and quinolone-resistant organisms are increasingly seen, even though
      their clinical significance is unclear. Fluoroquinolones (including ciprofloxacin
      and norfloxacin) used for short term (7 d) have the most robust evidence and are
      recommended in most expert guidelines. Short term intravenous cephalosporin
      (especially ceftriaxone), given in a hospital setting with prevalent quinolone
      resistant organisms, has been shown in studies to be beneficial, particularly in
      high risk patients with advanced cirrhosis. 

PMID- 24587657
TI  - Increased susceptibility to Trichuris muris infection and exacerbation of colitis
      in Mdr1a-/- mice.
AB  - AIM: To investigate the influence of Trichuris muris (T. muris) infection in a
      mouse model of genetic susceptibility to inflammatory bowel disease, Mdr1a-/-.
      METHODS: Mdr1a-/- mice were housed under specific pathogen free conditions to
      slow the development of colitis and compared to congenic FVB controls. Mice were
      infected with approximately 200 embryonated ova from T. muris and assessed for
      worm burden and histological and functional markers of gut inflammation on day 19
      post infection. RESULTS: Mdr1a-/- mice exhibited a marked increase in
      susceptibility to T. muris infection with a 10-fold increase in colonic worm
      count by day 19 pi compared to FVB controls. Prior to infection, Mdr1a-/-
      exhibited low-level mucosal inflammation with evidence of an enhanced Th1
      environment. T. muris infection accelerated the progression of colitis in Mdr1a-/
      as evidenced by marked increases in several indicators including histological
      damage score, mucosal CD+ T-cell and DC infiltration and dramatically increased
      production of pro-inflammatory cytokines. CONCLUSION: These data provide further
      evidence of the complex interaction between T. muris and an inflammatory bowel
      disease (IBD)-susceptible host which may have relevance to the application of
      helminth therapy in the treatment of human IBD.

PMID- 24587655
TI  - Laparoscopic approach to gastrointestinal malignancies: toward the future with
      caution.
AB  - After the rapid acceptance of laparoscopy to manage multiple benign diseases
      arising from gastrointestinal districts, some surgeons started to treat
      malignancies by the same way. However, if the limits of laparoscopy for benign
      diseases are mainly represented by technical issues, oncologic outcomes remain
      the foundation of any procedures to cure malignancies. Cancerous patients
      represent an important group with peculiar aspects including reduced survival
      expectancy, worsened quality of life due to surgery itself and adjuvant
      therapies, and challenging psychological impact. All these issues could,
      potentially, receive a better management with a laparoscopic surgical approach.
      In order to confirm such aspects, similarly to testing the newest weapons
      (surgical or pharmacologic) against cancer, long-term follow-up is always
      recommendable to assess the real benefits in terms of overall survival, cancer
      free survival and quality of life. Furthermore, it seems of crucial importance
      that surgeons will be correctly trained in specific oncologic principles of
      surgical oncology as well as in modern miniinvasive technologies. Therefore,
      laparoscopic treatment of gastrointestinal malignancies requires more caution and
      deep analysis of published evidences, as compared to those achieved for
      inflammatory bowel diseases, gastroesophageal reflux disease or diverticular
      disease. This review tries to examine the evidence available to date for the use
      of laparoscopy and robotics in malignancies arising from the gastrointestinal
      district. 

PMID- 24587658
TI  - Diet high in fructose leads to an overexpression of lipocalin-2 in rat fatty
      liver.
AB  - AIM: To explore lipocalin-2 (LCN-2) expression and its possible role and
      mechanism(s) of production in rat models of diet-inducible fatty liver. METHODS:
      Fatty liver was triggered in male Sprague-Dawley rats fed either with liquid
      Lieber-DeCarli (LDC) or LDC + 70% cal fructose (L-HFr) diet for 4 or 8 wk. Chow
      nourished animals served as controls. Hepatic expression of LCN-2 and other
      metabolic and inflammatory mediators was assessed by quantitative reverse
      transcription polymerase chain reaction and Western blotting. Serum LCN-2,
      fasting leptin, and lipid profile were evaluated via Enzyme-Linked Immunosorbent
      Assay, Radioimmunoassay, and colorimetric assays, respectively. The localization
      of LCN-2 in the liver was detected by using immunofluorescence staining.
      Furthermore, HE stain was used to evaluate hepatic fat degeneration and
      inflammation. RESULTS: Both LDC-fed and L-HFr-fed rat histologically featured
      fatty liver. In the liver, mRNA transcriptions of Mcp-1, a2-m, Il-8 and Glut5
      were increased in the L-HFr group at both time points (P < 0.001), while the
      transcription of Tlr4, Inos, and Tnf-alpha was significantly up-regulated at week
      4. Interestingly, hepatic Lcn-2 expression was 90-fold at week 4 and 507-fold at
      week 8 higher in L-HFr-subjected rats vs control (P < 0.001). In contrast to HDL
      cholesterol, systemic levels of LCN-2, fasting leptin and triglycerides were
      elevated in the L-HFr regimen (P < 0.001). Moreover, protein expression of
      hepatic LCN-2, CD14, phospho-MAPK, caspase-9, cytochrome c and 4-hydroxynonenal
      was increased in the L-HFr group. Conversely, the hepatic expression of PGC
      1alpha (a mitochondrial-biogenic protein) was reduced in the L-HFr category at
      week 8. The localization of LCN-2 in the liver was predominantly restricted to
      MPO+ granulocytes. CONCLUSION: Fructose diet up-regulates hepatic LCN-2
      expression, which correlates with the increased indicators of oxidative stress
      and mitochondrial dysfunction. The LCN-2 may be involved in liver protection.

PMID- 24587659
TI  - Sophocarpine attenuates liver fibrosis by inhibiting the TLR4 signaling pathway
      in rats.
AB  - AIM: To explore the effect of sophocarpine on experimental liver fibrosis and the
      potential mechanism involved. METHODS: Sophocarpine was injected
      intraperitoneally in two distinct rat hepatic fibrosis models induced either by
      dimethylnitrosamine or bile duct ligation. Masson's trichrome staining, Sirius
      red staining and hepatic hydroxyproline level were used for collagen
      determination. Primary hepatic stellate cells (HSCs) were isolated and treated
      with different concentrations of sophocarpine. Real-time reverse transcription
      polymerase chain reaction was used to detect the mRNA levels of fibrotic markers
      and cytokines. The expression of pathway proteins was measured by Western blot.
      The Cell Counting Kit-8 test was used to detect the proliferation rate of
      activated HSCs treated with a gradient concentration of sophocarpine. RESULTS:
      Sophocarpine decreased serum levels of aminotransferases and total bilirubin in
      rats under chronic insult. Moreover, administration of sophocarpine suppressed
      extracellular matrix deposition and prevented the development of hepatic
      fibrosis. Furthermore, sophocarpine inhibited the expression of alpha-smooth
      muscle actin (SMA), interleukin (IL)-6, transforming growth factor-beta1 (TGF
      beta1), Toll-like receptor 4 (TLR4), and extracellular-related kinase (ERK) in
      rats. Sophocarpine also down-regulated the mRNA expression of alpha-SMA, collagen
      I, collagen III, TGF-beta1, IL-6, tumor necrosis factor-alpha and monocyte
      chemoattractant protein-1, and decreased protein levels of TLR4, p-ERK, p-JNK, p
      P38 and p-IKK in vitro after Lipopolysaccharide induction. In addition,
      sophocarpine inhibited the proliferation of HSCs accompanied by a decrease in the
      expression of Cyclin D1. The protein level of proliferating cell nuclear antigen
      was decreased in activated HSCs following a gradient concentration of
      sophocarpine. CONCLUSION: Sophocarpine can alleviate liver fibrosis mainly by
      inhibiting the TLR4 pathway. Sophocarpine may be a potential chemotherapeutic
      agent for chronic liver diseases.

PMID- 24587660
TI  - Colonic manifestations of PTEN hamartoma tumor syndrome: case series and
      systematic review.
AB  - AIM: To investigate our clinical experience with the colonic manifestations of
      phosphatase and tensin homolog on chromosome ten (PTEN) hamartoma tumor syndrome
      (PHTS) and to perform a systematic literature review regarding the same. METHODS:
      This study was approved by the appropriate institutional review board prior to
      initiation. A clinical genetics database was searched for patients with PHTS or a
      component syndrome that received gastrointestinal endoscopy or pathology
      interpretation at our center. These patient's records were retrospectively
      reviewed for clinical characteristics (including family history and genetic
      testing), endoscopy results and pathology findings. We also performed a
      systematic review of the literature for case series of PHTS or component
      syndromes that reported gastrointestinal manifestations and investigations
      published after consensus diagnostic criteria were established in 1996. These
      results were compiled and reported. RESULTS: Eight patients from our institution
      met initial inclusion criteria. Of these, 5 patients underwent 4.2 colonoscopies
      at mean age 45.8 +/- 10.8 years. All were found to have colon polyps during their
      clinical course and polyp histology included adenoma, hyperplastic,
      ganglioneuroma and juvenile. No malignant lesions were identified. Two had
      multiple histologic types. One patient underwent colectomy due to innumerable
      polyps and concern for future malignant potential. Systematic literature review
      of PHTS patients undergoing endoscopy revealed 107 patients receiving colonoscopy
      at mean age 37.4 years. Colon polyps were noted in 92.5% and multiple colon polyp
      histologies were reported in 53.6%. Common polyp histologies included
      hyperplastic (43.6%), adenoma (40.4%), hamartoma (38.3%), ganglioneuroma (33%)
      and inflammatory (24.5%) polyps. Twelve (11.2%) patients had colorectal cancer at
      mean age 46.7 years (range 35-62). Clinical outcomes secondary to colon polyposis
      and malignancy were not commonly reported. CONCLUSION: PHTS has a high prevalence
      of colon polyposis with multiple histologic types. It should be considered a
      mixed polyposis syndrome. Systematic review found an increased prevalence of
      colorectal cancer and we recommend initiating colonoscopy for colorectal cancer
      surveillance at age 35 years.

PMID- 24587661
TI  - Risk factors for bleeding after endoscopic submucosal dissection of colorectal
      neoplasms.
AB  - AIM: To investigate the risk factors for delayed bleeding following endoscopic
      submucosal dissection (ESD) treatment for colorectal neoplasms. METHODS: We
      retrospectively reviewed the medical records of 317 consecutive patients with 325
      lesions who underwent ESD for superficial colorectal neoplasms at our hospital
      from January 2009 to June 2013. Delayed post-ESD bleeding was defined as bleeding
      that resulted in overt hematochezia 6 h to 30 d after ESD and the observation of
      bleeding spots as confirmed by repeat colonoscopy or a required blood
      transfusion. We analyzed the relationship between risk factors for delayed
      bleeding following ESD and the following factors using univariate and
      multivariate analyses: age, gender, presence of comorbidities, use of
      antithrombotic drugs, use of intravenous heparin, resected specimen size, lesion
      size, lesion location, lesion morphology, lesion histology, the device used,
      procedure time, and the presence of significant bleeding during ESD. RESULTS:
      Delayed post-ESD bleeding was found in 14 lesions from 14 patients (4.3% of all
      specimens, 4.4% patients). Patients with episodes of delayed post-ESD bleeding
      had a mean hemoglobin decrease of 2.35 g/dL. All episodes were treated
      successfully using endoscopic hemostatic clips. Emergency surgery was not
      required in any of the cases. Blood transfusion was needed in 1 patient (0.3%).
      Univariate analysis revealed that lesions located in the cecum (P = 0.012) and
      the presence of significant bleeding during ESD (P = 0.024) were significantly
      associated with delayed post-ESD bleeding. The risk of delayed bleeding was
      higher for larger lesion sizes, but this trend was not statistically significant.
      Multivariate analysis revealed that lesions located in the cecum (OR = 7.26,
      95%CI: 1.99-26.55, P = 0.003) and the presence of significant bleeding during ESD
      (OR = 16.41, 95%CI: 2.60-103.68, P = 0.003) were independent risk factors for
      delayed post-ESD bleeding. CONCLUSION: Location in the cecum and significant
      bleeding during ESD predispose patients to delayed post-procedural bleeding.
      Therefore, careful and additional management is recommended for these patients.

PMID- 24587662
TI  - Is the AIMS65 score useful in predicting outcomes in peptic ulcer bleeding?
AB  - AIM: To evaluate the applicability of AIMS65 scores in predicting outcomes of
      peptic ulcer bleeding. METHODS: This was a retrospective study in a single center
      between January 2006 and December 2011. We enrolled 522 patients with upper
      gastrointestinal haemorrhage who visited the emergency room. High-risk patients
      were regarded as those who had re-bleeding within 30 d from the first endoscopy
      as well as those who died within 30 d of visiting the Emergency room. A total of
      149 patients with peptic ulcer bleeding were analysed, and the AIMS65 score was
      used to retrospectively predict the high-risk patients. RESULTS: A total of 149
      patients with peptic ulcer bleeding were analysed. The poor outcome group
      comprised 28 patients [male: 23 (82.1%) vs female: 5 (10.7%)] while the good
      outcome group included 121 patients [male: 93 (76.9%) vs female: 28 (23.1%)]. The
      mean age in each group was not significantly different. The mean serum albumin
      levels in the poor outcome group were slightly lower than those in the good
      outcome group (P = 0.072). For the prediction of poor outcome, the AIMS65 score
      had a sensitivity of 35.5% (95%CI: 27.0-44.8) and a specificity of 82.1% (95%CI:
      63.1-93.9) at a score of 0. The AIMS65 score was insufficient for predicting
      outcomes in peptic ulcer bleeding (area under curve = 0.571; 95%CI: 0.49-0.65).
      CONCLUSION: The AIMS65 score may therefore not be suitable for predicting
      clinical outcomes in peptic ulcer bleeding. Low albumin levels may be a risk
      factor associated with high mortality in peptic ulcer bleeding.

PMID- 24587663
TI  - Intravenous iron supplementation may be superior to observation in acute
      isovolemic anemia after gastrectomy for cancer.
AB  - AIM: To determine whether the application of post-operative intravenous (IV)-iron
      for acute isovolemic anemia after gastrectomy for cancer may be effective.
      METHODS: Among 2078 gastric cancer patients who underwent surgery between
      February 2007 and August 2009 at the National Cancer Center Korea, 368 patients
      developed post-operative anemia [hemoglobin-(Hb)-level < 9 g/dL] within the first
      postoperative week. Patients requiring transfusions were excluded. IV-iron was
      administered to 63 patients (iron group). Sixty patients were observed without
      treatment (observation group). The clinical outcomes of the groups were compared
      concerning clinicopathologic data, morbidity, and changes in Hb levels using
      Fisher's exact test, Student's t-test and the Z-test. RESULTS: The initial Hb
      level was higher in the iron group than in the observation group (7.3 +/- 1.0
      g/dL vs 8.4 +/- 0.5 g/dL, P < 0.001). The slope of the changes in the Hb level
      was significantly higher in the iron group than in the observation group (0.648
      +/- 0.054 vs 0.349 +/- 0.038, P < 0.001). The Hb level 1 and 3 mo post
      operatively increased from 10.7 +/- 1.3 to 11.9 +/- 1.3 g/dL in the iron group (P
      = 0.033) and from 10.1 +/- 1.0 to 10.8 +/- 1.4 g/dL in the observation group (P <
      0.001). The postoperative hospital stay was significantly longer in the iron
      group than in the observation group (10.5 +/- 6.8 d vs 7.6 +/- 5.5 d, P = 0.011).
      There were no significant differences in the major and surgical complications
      between the groups (6.3% vs 13.3%, P = 0.192; 9.5% vs 3.3%, P = 0.164).
      CONCLUSION: IV-iron supplementation may be an effective treatment for post
      operative isovolemic post-gastrectomy anemia and may be a better alternative than
      observation.

PMID- 24587664
TI  - Statins and the risk of colorectal cancer: an updated systematic review and meta
      analysis of 40 studies.
AB  - AIM: To investigate the association between statin use and colorectal cancer
      risk, we conducted an updated meta-analysis of published studies. METHODS: We
      performed a comprehensive search for studies published up to July 2013. Eligible
      studies for this meta-analysis were either randomized controlled trials (RCTs) or
      observational studies (case-control or cohort) evaluating any exposure to statins
      and the risk of colorectal cancer. Two reviewers selected studies based on
      predefined inclusion criteria, and abstracted the data. Pooled relative risk (RR)
      estimates with their 95%CI were calculated using fixed- and random-effects
      models. Then, we assessed the potential presence of publication bias and between
      studies heterogeneity. To evaluate the results, we also performed a "leave-one
      out" sensitivity analysis. RESULTS: A total of 40 studies, involving more than
      eight million subjects, contributed to the analysis. They were grouped on the
      basis of study design and, consequently, three separate meta-analyses were
      conducted. A similar modest reduction in the risk of colorectal cancer with
      statin use was observed, which was not statistically significant among RCTs (RR =
      0.89, 95%CI: 0.74-1.07; n = 8), but reached statistical significance among cohort
      studies (RR = 0.91, 95%CI: 0.83-1.00; n = 13) and case-control studies (RR =
      0.92, 95%CI: 0.87-0.98; n = 19). While we did not find significant evidence of
      selective outcome reporting or publication bias, substantial heterogeneity was
      detected, mainly among the observational studies. The sensitivity analysis
      confirmed the stability of our results. CONCLUSION: A modest reduction in risk of
      colorectal cancer among statin users cannot be disproved. Further targeted
      research is warranted.

PMID- 24587665
TI  - Effectiveness of acupuncture to treat irritable bowel syndrome: a meta-analysis.
AB  - AIM: To evaluate the efficacy of acupuncture for treatment of irritable bowel
      syndrome (IBS) through meta-analysis of randomized controlled trials. METHODS: We
      searched MEDLIINE, PubMed, Scopus, Web of Science, and Cochrane Central Register
      of Controlled Trials from 1966 to February 2013 for double-blind, placebo
      controlled trials investigating the efficacy of acupuncture in the management of
      IBS. Studies were screened for inclusion based on randomization, controls, and
      measurable outcomes reported. We used the modified Jadad score for assessing the
      quality of the articles. STATA 11.0 and Revman 5.0 were used for meta-analysis.
      Publication bias was assessed by Begg's and Egger's tests. RESULTS: Six
      randomized, placebo-controlled clinical trials met the criteria and were included
      in the meta-analysis. The modified Jadad score of the articles was > 3, and five
      articles were of high quality. We analyzed the heterogeneity and found that these
      studies did not cause heterogeneity in our meta-analysis. Begg's test showed P =
      0.707 and Egger's test showed P = 0.334. There was no publication bias in our
      meta-analysis (Begg's test, P = 0.707; Egger's test, P = 0.334). From the forest
      plot, the diamond was on the right side of the vertical line and did not
      intersect with the line. The pooled relative risk for clinical improvement with
      acupuncture was 1.75 (95%CI: 1.24-2.46, P = 0.001). Using the two different
      systems of STATA 11.0 and Revman 5.0, we confirmed the significant efficacy of
      acupuncture for treating IBS. CONCLUSION: Acupuncture exhibits clinically and
      statistically significant control of IBS symptoms.

PMID- 24587666
TI  - Recurrent gastrointestinal bleeding and hepatic infarction after liver biopsy.
AB  - Hepatic artery pseudoaneurysms (HAP) are rare events, particularly after liver
      biopsy, but can be associated with serious complications. Therefore a high
      suspicion is necessary for timely diagnosis and appropriate treatment. We report
      on a case of HAP that potentially formed after a liver biopsy in a patient with
      sarcoidosis. The HAP in our case was virtually undetectable initially by
      angiography but resulted in several complications including recurrent
      gastrointestinal bleeding, hemorrhagic cholecystitis and finally hepatic
      infarction with abscess formation until it became detectable at a size of 5-mm.
      The patient remains asymptomatic over a year after endovascular embolization of
      the HAP. In this report, we demonstrate that a small HAP can avoid detection by
      angiography at an early stage while being symptomatic for a prolonged course. A
      high clinical suspicion with a close clinical/radiological follow-up is needed in
      symptomatic patients with history of liver biopsy despite initial negative work
      up. Once diagnosed, HAP can be safely and effectively treated by endovascular
      embolization. 

PMID- 24587667
TI  - Pancreatic pseudocystocolonic fistula treated without surgical or endoscopic
      intervention.
AB  - We report here a case of pancreatic pseudocystocolic fistula that was treated
      without surgical or endoscopic intervention. A 76-year-old woman, presenting with
      a fever and epigastric pain, was referred to our institution. Three months prior
      to this admission, the patient had been admitted to the hospital for acute
      pancreatitis. Abdominal computerized tomography (CT) revealed a 9 cm pseudocyst
      containing air, and a fistular opening was observed via colonoscopy. After
      colonoscopy, the abdominal pain was slightly improved, the fever subsided and
      laboratory results showed decreased C-reactive protein levels. The observed
      improvement was likely due to the cleansing of the bowel, which induced
      spontaneous drainage from the pseudocyst into the colon. Antibiotic therapy was
      administered and daily bowel cleansing was performed using a polyethylene glycol
      solution. After three weeks, a follow-up CT revealed that the size of the
      pseudocyst had decreased significantly from 9 to 5.3 cm. In addition, laboratory
      tests were improved. The patient was able to resume a normal diet and was
      discharged in good overall health from the hospital, without aggravation of the
      symptoms. A colonoscopy performed 3 mo later and a follow-up CT performed 6 mo
      later confirmed that both the fistula and pseudocyst had completely disappeared. 

PMID- 24587668
TI  - Colorectal cancer surveillance: what's new and what's next.
AB  - The accumulated evidence from two decades of randomized controlled trials has not
      yet resolved the question of how best to monitor colorectal cancer (CRC)
      survivors for early detection of recurrent and metachronous disease or even
      whether doing so has its intended effect. A new wave of trial data in the coming
      years and an evolving knowledge of relevant biomarkers may bring us closer to
      understanding what surveillance strategies are most effective for a given subset
      of patients. To best apply these insights, a number of important research
      questions need to be addressed, and new decision making tools must be developed.
      In this review, we summarize available randomized controlled trial evidence
      comparing alternative surveillance testing strategies, describe ongoing trials in
      the area, and compare professional society recommendations for surveillance. In
      addition, we discuss innovations relevant to CRC surveillance and outline a
      research agenda which will inform a more risk-stratified and personalized
      approach to follow-up. 

PMID- 24587669
TI  - Intestinal stem cells and the colorectal cancer microenvironment.
AB  - Colorectal cancer (CRC) remains a highly fatal condition in part due to its
      resilience to treatment and its propensity to spread beyond the site of primary
      occurrence. One possible avenue for cancer to escape eradication is via stem-like
      cancer cells that, through phenotypic heterogeneity, are more resilient than
      other tumor constituents and are key contributors to cancer growth and
      metastasis. These proliferative tumor cells are theorized to possess many
      properties akin to normal intestinal stem cells. Not only do these CRC "stem"
      cells demonstrate similar restorative ability, they also share many cell pathways
      and surface markers in common, as well as respond to the same key niche stimuli.
      With the improvement of techniques for epithelial stem cell identification, our
      understanding of CRC behavior is also evolving. Emerging evidence about cellular
      plasticity and epithelial mesenchymal transition are shedding light onto
      metastatic CRC processes and are also challenging fundamental concepts about
      unidirectional epithelial proliferation. This review aims to reappraise evidence
      supporting the existence and behavior of CRC stem cells, their relationship to
      normal stem cells, and their possible dependence on the stem cell niche. 

PMID- 24587670
TI  - Targeting cell death signaling in colorectal cancer: current strategies and
      future perspectives.
AB  - The evasion from controlled cell death induction has been considered as one of
      the hallmarks of cancer cells. Defects in cell death signaling are a fundamental
      phenomenon in colorectal cancer. Nearly any non-invasive cancer treatment finally
      aims to induce cell death. However, apoptosis resistance is the major cause for
      insufficient therapeutic success and disease relapse in gastrointestinal
      oncology. Various compounds have been developed and evaluated with the aim to
      meet with this obstacle by triggering cell death in cancer cells. The aim of this
      review is to illustrate current approaches and future directions in targeting
      cell death signaling in colorectal cancer. The complex signaling network of
      apoptosis will be demonstrated and the "druggability" of targets will be
      identified. In detail, proteins regulating mitochondrial cell death in colorectal
      cancer, such as Bcl-2 and survivin, will be discussed with respect to potential
      therapeutic exploitation. Death receptor signaling and targeting in colorectal
      cancer will be outlined. Encouraging clinical trials including cell death based
      targeted therapies for colorectal cancer are under way and will be demonstrated.
      Our conceptual understanding of cell death in cancer is rapidly emerging and new
      types of controlled cellular death have been identified. To meet this progress in
      cell death research, the implication of autophagy and necroptosis for colorectal
      carcinogenesis and therapeutic approaches will also be depicted. The main focus
      of this topic highlight will be on the revelation of the complex cell death
      concepts in colorectal cancer and the bridging from basic research to clinical
      use. 

PMID- 24587671
TI  - Colorectal cancer and lymph nodes: the obsession with the number 12.
AB  - Lymphadenectomy of colorectal cancer is a decisive factor for the prognostic and
      therapeutic staging of the patient. For over 15 years, we have asked ourselves if
      the minimum number of 12 examined lymph nodes (LNs) was sufficient for the
      prevention of understaging. The debate is certainly still open if we consider
      that a limit of 12 LNs is still not the gold standard mainly because the research
      methodology of the first studies has been criticized. Moreover many authors
      report that to date both in the United States and Europe the number "12" target
      is uncommon, not adequate, or accessible only in highly specialised centres. It
      should however be noted that both the pressing nature of the debate and the
      dissemination of guidelines have been responsible for a trend that has allowed
      for a general increase in the number of LNs examined. There are different
      variables that can affect the retrieval of LNs. Some, like the surgeon, the
      surgery, and the pathology exam, are without question modifiable; however, other
      both patient and disease-related variables are non-modifiable and pose the
      question of whether the minimum number of examined LNs must be individually
      assigned. The lymph nodal ratio, the sentinel LNs and the study of the biological
      aspects of the tumor could find valid application in this field in the near
      future.

PMID- 24587672
TI  - New genes emerging for colorectal cancer predisposition.
AB  - Colorectal cancer (CRC) is one of the most frequent neoplasms and an important
      cause of mortality in the developed world. This cancer is caused by both genetic
      and environmental factors although 35% of the variation in CRC susceptibility
      involves inherited genetic differences. Mendelian syndromes account for about 5%
      of the total burden of CRC, with Lynch syndrome and familial adenomatous
      polyposis the most common forms. Excluding hereditary forms, there is an
      important fraction of CRC cases that present familial aggregation for the disease
      with an unknown germline genetic cause. CRC can be also considered as a complex
      disease taking into account the common disease-commom variant hypothesis with a
      polygenic model of inheritance where the genetic components of common complex
      diseases correspond mostly to variants of low/moderate effect. So far, 30 common,
      low-penetrance susceptibility variants have been identified for CRC. Recently,
      new sequencing technologies including exome- and whole-genome sequencing have
      permitted to add a new approach to facilitate the identification of new genes
      responsible for human disease predisposition. By using whole-genome sequencing,
      germline mutations in the POLE and POLD1 genes have been found to be responsible
      for a new form of CRC genetic predisposition called polymerase proofreading
      associated polyposis.

PMID- 24587673
TI  - Perioperative anemia management in colorectal cancer patients: a pragmatic
      approach.
AB  - Anemia, usually due to iron deficiency, is highly prevalent among patients with
      colorectal cancer. Inflammatory cytokines lead to iron restricted erythropoiesis
      further decreasing iron availability and impairing iron utilization. Preoperative
      anemia predicts for decreased survival. Allogeneic blood transfusion is widely
      used to correct anemia and is associated with poorer surgical outcomes, increased
      post-operative nosocomial infections, longer hospital stays, increased rates of
      cancer recurrence and perioperative venous thromboembolism. Infections are more
      likely to occur in those with low preoperative serum ferritin level compared to
      those with normal levels. A multidisciplinary, multimodal, individualized
      strategy, collectively termed Patient Blood Management, minimizes or eliminates
      allogeneic blood transfusion. This includes restrictive transfusion policy,
      thromboprophylaxis and anemia management to improve outcomes. Normalization of
      preoperative hemoglobin levels is a World Health Organization recommendation.
      Iron repletion should be routinely ordered when indicated. Oral iron is poorly
      tolerated with low adherence based on published evidence. Intravenous iron is
      safe and effective but is frequently avoided due to misinformation and
      misinterpretation concerning the incidence and clinical nature of minor infusion
      reactions. Serious adverse events with intravenous iron are extremely rare. Newer
      formulations allow complete replacement dosing in 15-60 min markedly facilitating
      care. Erythropoiesis stimulating agents may improve response rates. A
      multidisciplinary, multimodal, individualized strategy, collectively termed
      Patient Blood Management used to minimize or eliminate allogeneic blood
      transfusion is indicated to improve outcomes. 

PMID- 24587674
TI  - Clock genes: their role in colorectal cancer.
AB  - Clock genes create a complicated molecular time-keeping system consisting of
      multiple positive and negative feedback loops at transcriptional and
      translational levels. This circadian system coordinates and regulates multiple
      cellular procedures implicated in cancer development such as metabolism, cell
      cycle and DNA damage response. Recent data support that molecules such as CLOCK1,
      BMAL1 and PER and CRY proteins have various effects on c-Myc/p21 and Wnt/beta
      catenin pathways and influence multiple steps of DNA damage response playing a
      critical role in the preservation of genomic integrity in normal and cancer
      cells. Notably, all these events have already been related to the development and
      progression of colorectal cancer (CRC). Recent data highlight critical
      correlations between clock genes' expression and pathogenesis, progression,
      aggressiveness and prognosis of CRC. Increased expression of positive regulators
      of this circadian system such as BMAL1 has been related to decrease overall
      survival while decreased expression of negative regulators such as PER2 and PER3
      is connected with poorer differentiation, increased aggressiveness and worse
      prognosis. The implications of these molecules in DNA repair systems explain
      their involvement in the development of CRC but at the same time provide us with
      novel targets for modern therapeutic approaches for patients with advanced CRC.

PMID- 24587675
TI  - Stereotactic body radiotherapy for oligo-recurrence within the nodal area from
      colorectal cancer.
AB  - Recurrence of colorectal cancer (CRC) often presents as solitary metastases,
      oligometastases or oligo-recurrence. Surgical resection became the preferred
      treatment for patients with CRC lung and hepatic metastases. However, surgical
      treatment for oligo-recurrence within nodal area is not a widely accepted
      treatment due to due to their relative rarity and high postoperative morbidity.
      Stereotactic body radiotherapy (SBRT) is one of the emerging radiation treatment
      techniques in which a high radiation dose can be delivered to the tumor. High
      dose SBRT can ablate the tumor with an efficacy similar to that achieved with
      surgery, especially for small tumors. However, there have been very few studies
      on SBRT for oligo-recurrence within nodal area, although several studies have
      evaluated the role of SBRT in the treatment of liver and lung metastases from
      CRC. This article reviews the current clinical status of and treatment methods
      for oligo-recurrence within nodal area from CRC, with particular emphasis on
      SBRT.

PMID- 24587677
TI  - Current issues in locally advanced colorectal cancer treated by preoperative
      chemoradiotherapy.
AB  - In patients with locally advanced rectal cancer, preoperative chemoradiotherapy
      has proven to significantly improve local control and cause lower treatment
      related toxicity compared with postoperative adjuvant treatment. Preoperative
      chemoradiotherapy followed by total mesorectal excision or tumor specific
      mesorectal excision has evolved as the standard treatment for locally advanced
      rectal cancer. The paradigm shift from postoperative to preoperative therapy has
      raised a series of concerns however that have practical clinical implications.
      These include the method used to predict patients who will show good response,
      sphincter preservation, the application of conservative management such as local
      excision or "wait-and-watch" in patients obtaining a good response following
      preoperative chemoradiotherapy, and the role of adjuvant chemotherapy. This
      review addresses these current issues in patients with locally advanced rectal
      cancer treated by preoperative chemoradiotherapy. 

PMID- 24587676
TI  - CT colonography in the diagnosis and management of colorectal cancer: emphasis on
      pre- and post-surgical evaluation.
AB  - This article addresses the use of computed tomographic colonography (CTC) for the
      diagnosis and management of colorectal cancer, focusing on presurgical evaluation
      of the colon proximal to an occlusive cancer and surveillance after cancer
      resection surgery. The key evidences accumulated in the literature and future
      work needed are summarized. CTC is a technically robust and the most practical
      method to evaluate the colon proximal to an occlusive cancer, which prevents
      colonoscopic examination past the occlusion, either before or after metallic
      stent placement. The high sensitivity of CTC for detecting cancers and advanced
      adenomas in the proximal colon can help prevent additional surgical procedures in
      patients showing negative results. However, the accuracy of CTC for
      distinguishing intramural cancers from adenomas is low, and the technique is
      limited in guiding management when a medium-sized lesion that do not show
      invasive features such as pericolic extension or nodal metastasis is found in the
      proximal colon. A maximal diameter >= 15 mm has been proposed as a criterion for
      surgical removal of proximal lesions. However, this needs to be verified in a
      larger cohort. In addition, the influence of presurgical CTC results on the
      current post-cancer resection colonic surveillance timeline remains to be
      determined. CTC can be readily added to the routine abdominopelvic CT in the form
      of contrast-enhanced CTC, which can serve as an effective stand-alone tool for
      post-cancer resection surveillance of both the colorectum and extracolonic
      organs. Although the accuracy of CTC has been demonstrated, its role in the
      current colonoscopy-based postoperative colonic surveillance protocols remains to
      be determined. Readers of CTC also need to be knowledgeable on the colonic
      lesions that are unique to the postoperative colon. 

PMID- 24587678
TI  - Targeted therapy in gastric cancer: personalizing cancer treatment based on
      patient genome.
AB  - Gastric cancer is the second leading cause of cancer-related deaths worldwide.
      Conventional cytotoxic chemotherapy has limited efficacy for metastatic gastric
      cancer, with an overall survival of approximately ten months. Recent advances in
      high-throughput technologies have enabled the implementation of personalized
      cancer therapy for high-risk patients. The use of such high-throughput
      technologies, including microarray and next generation sequencing, have promoted
      the discovery of novel targets that offer new treatment strategies for patients
      lacking other therapeutic options. Many molecular pathways are currently under
      investigation as therapeutic targets in gastric cancer, including those related
      to the epidermal growth factor receptor family, the mesenchymal-epithelial
      transition factor axis, and the phosphatidylinositol 3-kinase-AKT-mammalian
      target of rapamycin factors. Advances in molecular diagnostic tools further
      support the discovery of new molecular targets. Limitations exist, however; not
      all patients can be tested for biomarkers, and numerous challenges hamper
      implementation of targeted therapy in clinical settings. Indeed, the scale of
      tumor genomic profiling is rapidly outpacing our ability to appropriately
      synthesize all the information in order to optimally refine patient care.
      Therefore, clinicians must continue to educate themselves regarding new tools and
      frameworks, and to utilize multidisciplinary team science, comprised of
      oncologists, geneticists, pathologists, biologists and bioinformaticians, to
      successfully implement this genomic approach therapeutically. 

PMID- 24587679
TI  - Longitudinal analysis of inflammation and microbiota dynamics in a model of mild
      chronic dextran sulfate sodium-induced colitis in mice.
AB  - AIM: To characterize longitudinally the inflammation and the gut microbiota
      dynamics in a mouse model of dextran sulfate sodium (DSS)-induced colitis.
      METHODS: In animal models, the most common method used to trigger colitis is
      based on the oral administration of the sulfated polysaccharides DSS. The murine
      DSS colitis model has been widely adopted to induce severe acute, chronic or semi
      chronic colitis, and has been validated as an important model for the translation
      of mice data to human inflammatory bowel disease (IBD). However, it is now clear
      that models characterized by mild intestinal damage are more accurate for
      studying the effects of therapeutic agents. For this reason, we have developed a
      murine model of mild colitis to study longitudinally the inflammation and
      microbiota dynamics during the intestinal repair processes, and to obtain data
      suitable to support the recovery of gut microbiota-host homeostasis. RESULTS: All
      plasma cytokines evaluated, except IL-17, began to increase (P < 0.05), after 7 d
      of DSS administration. IL-17 only began to increase 4 d after DSS withdrawal. IL
      1beta and IL-17 continue to increase during the recovery phase, even when
      clinical signs of colitis had disappeared. IL-6, IL-10 and IFN-gamma reached
      their maxima 4 d after DSS withdrawal and decreased during the late recovery
      phase. TNFalpha reached a peak (a three- fold increase, P < 0.05), after which it
      slightly decreased, only to increase again close to the end of the recovery
      phase. DSS administration induced profound and rapid changes in the mice gut
      microbiota. After 3 d of DSS administration, we observed a major reduction in
      Bacteroidetes/Prevotella and a corresponding increase in Bacillaceae, with
      respect to control mice. In particular, Bacteroidetes/Prevotella decreased from a
      relative abundance of 59.42%-33.05%, while Bacillaceae showed a concomitant
      increase from 2.77% to 10.52%. Gut microbiota rapidly shifted toward a healthy
      profile during the recovery phase and returned normal 4 d after DSS withdrawal.
      Cyclooxygenase 2 expression started to increase 4 d after DSS withdrawal (P <
      0.05), when dysbiosis had recovered, and continued to increase during the
      recovery phase. Taken together, these data indicated that a chronic phase of
      intestinal inflammation, characterized by the absence of dysbiosis, could be
      obtained in mice using a single DSS cycle. CONCLUSION: Dysbiosis contributes to
      the local and systemic inflammation that occurs in the DSS model of colitis;
      however, chronic bowel inflammation is maintained even after recovery from
      dysbiosis.

PMID- 24587680
TI  - Chloride intracellular channel 1 regulates colon cancer cell migration and
      invasion through ROS/ERK pathway.
AB  - AIM: To investigate the mechanisms of chloride intracellular channel 1 (CLIC1) in
      the metastasis of colon cancer under hypoxia-reoxygenation (H-R) conditions.
      METHODS: Fluorescent probes were used to detect reactive oxygen species (ROS) in
      LOVO cells. Wound healing assay and transwell assay were performed to examine the
      migration and invasion of LOVO cells. Expression of CLIC1 mRNA and protein, p
      ERK, MMP-2 and MMP-9 proteins was analyzed by reverse transcription-polymerase
      chain reaction and Western blot. METHODS: H-R treatment increased the
      intracellular ROS level in LOVO cells. The mRNA and protein expression of CLIC1
      was elevated under H-R conditions. Functional inhibition of CLIC1 markedly
      decreased the H-R-enhanced ROS generation, cell migration, invasion and
      phosphorylation of ERK in treated LOVO cells. Additionally, the expression of MMP
      2 and MMP-9 could be regulated by CLIC1-mediated ROS/ERK pathway. CONCLUSION: Our
      results suggest that CLIC1 protein is involved in the metastasis of colon cancer
      LOVO cells via regulating the ROS/ERK pathway in the H-R process.

PMID- 24587681
TI  - Protective effects of D-002 on experimentally induced gastroesophageal reflux in
      rats.
AB  - AIM: To investigate the effects of beeswax alcohols (D-002) on the esophageal
      damage induced by gastroesophageal reflux (GER) in rats. METHODS: Sixty male rats
      were randomized into six groups (10 rats/group): a negative control and five
      groups with experimentally induced GER: a positive vehicle control, three treated
      with D-002 (25, 100 and 200 mg/kg, respectively), and one with omeprazole 10
      mg/kg. All treatments were given by gastric gavage. One hour after dosing, GER
      was produced by simultaneous ligation of the pyloric end and the forestomach.
      Esophageal lesions index (ELI), gastric secretion volume and acidity, and
      esophageal malondialdehyde (MDA) and sulfhydryl (SH) group concentrations were
      measured. Statistical significance was considered at P < 0.05. RESULTS: As
      compared to the negative control, the positive control group exhibited increased
      ELI (5.2 +/- 0.33 vs 0 +/- 0, P = 0.0003), gastric secretion volume (2.69 +/-
      0.09 vs 0.1 +/- 0.0, P = 0.0003) and acidity (238 +/- 19.37 vs 120.0 +/- 5.77, P
      = 0.001), and esophageal concentrations of MDA (2.56 +/- 0.1 vs 1.76 +/- 0.28, P
      = 0.001) and SH groups (1.02 +/- 0.05 vs 0.56 +/- 0.08, P = 0.0003). D-002 (25,
      100 and 200 mg/kg) reduced ELI (3.36 +/- 0.31, 2.90 +/- 0.46 and 2.8 +/- 0.23,
      respectively) vs the positive control (5.2 +/- 0.33) (P = 0.004; P = 0.002; P =
      0.001, respectively). There were no significant changes in acidity with D-002
      treatment, and only the highest dose reduced the volume of the gastric secretion
      (1.92 +/- 0.25) vs the positive control (2.69 +/- 0.09, P = 0.013). D-002 (25,
      100 and 200 mg/kg) lowered the esophageal MDA (2.05 +/- 0.16, 1.98 +/- 0.22 and
      1.93 +/- 0.22, respectively) (P = 0.01; P = 0.03; P = 0.03, respectively) and SH
      group concentration (0.87 +/- 0.06, 0.79 +/- 0.08 and 0.77 +/- 0.06,
      respectively) (P = 0.04; P = 0.04; P = 0.02) vs the positive control (2.56 +/-
      0.10 and 1.02 +/- 0.05, respectively). Omeprazole decreased ELI (2.54 +/- 0.47),
      gastric secretion volume (1.97 +/- 0.14) and acidity (158.5 +/- 22.79),
      esophageal MDA (1.87 +/- 0.13) and SH group (0.72 +/- 0.05) concentrations vs the
      positive control (P = 0.002; P = 0.001; P = 0.02; P = 0.003; P = 0.002,
      respectively). CONCLUSION: Acute oral administration of D-002 decreased
      macroscopic esophageal lesions and oxidative stress in rats with experimentally
      induced GER, without modifying gastric secretion acidity.

PMID- 24587682
TI  - ZD 7288, an HCN channel blocker, attenuates chronic visceral pain in irritable
      bowel syndrome-like rats.
AB  - AIM: To investigate the effects of ZD 7288, a hyperpolarization-activated cyclic
      nucleotide-gated (HCN) channel blocker, on rats with chronic visceral pain.
      METHODS: Rats with visceral hypersensitivity were generated using neonatal colon
      irritation during postnatal days 8-15 as described previously. Visceral
      hypersensitivity was evaluated using electromyographic (EMG) responses of
      abdominal external oblique muscles to 20-80 mmHg colorectal distentions (CRD).
      Abdominal withdrawal reflex (AWR) scores and pain thresholds were also detected
      in adult rats. Different doses of ZD 7288 (25, 50, and 100 nmol/L) were
      intrathecally administered in rats to study the role of spinal HCN channel in
      chronic visceral hypersensitivity. RESULTS: EMG responses to 20-80 mmHg CRD and
      AWR scores under 20-60 mmHg CRD significantly increased in rats with visceral
      hypersensitivity compared to control rats (P < 0.05). The pain threshold in rats
      with visceral hypersensitivity significantly decreased compared to control rats
      (P < 0.05). Treatment with 50-100 nmol/L ZD 7288 significantly inhibited EMG
      responses (16%-62%, 80-20 mmHg CRD, P < 0.05) and AWR scores (24%-37%, 40-20 mmHg
      CRD, P < 0.05; 12%-61%, 80-20 mmHg CRD, P < 0.05, respectively), and
      significantly increased pain thresholds (32%-77%, P < 0.05). CONCLUSION: Spinal
      HCN channels may play an important role in chronic visceral hypersensitivity.

PMID- 24587683
TI  - 3.0T 31P MR spectroscopy in assessment of response to antiviral therapy for
      chronic hepatitis C.
AB  - AIM: To investigate the utility of phosphorus-31 (31P) magnetic resonance
      spectroscopy (MRS) as a noninvasive test for assessment of response to interferon
      and ribavirin treatment in patients with different severities of hepatitis C
      virus infection. METHODS: Sixty chronic hepatitis C patients undergoing antiviral
      therapy with interferon and ribavirin underwent 31P MRS at 3.0T before treatment,
      6 mo after the start of treatment, and 1 year after the start of treatment.
      RESULTS: The phosphomonoester (PME)/phosphodiester (PDE) ratio at 6 mo after the
      start of antiviral therapy in the Child-Pugh B and C groups were significantly
      higher than those before therapy, but this was not seen in the Child-Pugh A
      group. In the antiviral therapy group, the PME/PDE ratios had decreased on follow
      up MR spectroscopy. However, in the virological nonresponder group, the PME/PDE
      ratios on follow-up imaging were similar to the baseline values. CONCLUSION: 31P
      MRS can be used to provide biochemical information on hepatic metabolic
      processes. This study indicates that the PME/PDE ratio can be used as an
      indicator of response to antiviral treatment in chronic hepatitis C patients.

PMID- 24587684
TI  - Pleomorphic hepatocellular carcinoma following consumption of hypericum
      perforatum in alcoholic cirrhosis.
AB  - Hepatocellular carcinoma (HCC) often develops in patients with underlying liver
      disease, yet HCC with syncytial giant cells (SGCs) is extremely rare. Herein, we
      report a 55-year-old man with a 6-year history of alcoholic cirrhosis who during
      his regular checkup presented with marked elevation of alpha-fetoprotein.
      Clinical examination and imaging analyses revealed a tumor-like lesion in segment
      4 of the liver, which was removed by limited wedge resection. Histological
      analysis by hematoxylin and eosin staining indicated pleomorphic and atypical
      nodules, with some SGCs, embedded within the boundaries of the neoplastic lesion.
      The adjacent liver parenchyma showed microvesicular steatosis, pericellular
      fibrosis, and moderate hemosiderin accumulation (grade 2, as determined by
      Prussian blue iron stain) in hepatocytes and Kupffer cells but no copper
      accumulation (as determined by orcein stain). Immunohistochemical analysis showed
      hepatocyte antigen-positive staining for the neoplastic cells and SGCs. The
      diagnosis was made for cirrhosis-related HCC with SGCs. The previous reports of
      pleomorphic HCC have featured osteoclast-like (i.e., mesenchymal type) giant
      cells, making this case of epithelial type giant cells very rare. The patient's 6
      month history of hypericum perforatum/St John's wort self-medication may have
      prompted the cirrhosis or HCC progression or the unusual SGC manifestation.

PMID- 24587685
TI  - Ileo-colonic intussusception secondary to small-bowel lipomatosis: a case report.
AB  - Intestinal lipomatosis is a rare disease with an incidence at autopsy ranging
      from 0.04% to 4.5%. Because the lipomas are diffusely distributed in the
      intestine, most patients are symptom-free, and invasive intervention is not
      advised by most doctors. Here, we describe a case with intussusception due to
      small-bowel lipomatosis. Partial small bowel resection and anastomosis were
      performed because the intestinal wall was on the verge of perforation. This case
      indicates that regular follow-up is necessary and endoscopic treatment should be
      considered to avoid surgical procedures if the lipoma is large enough to cause
      intestinal obstruction. 

PMID- 24587687
TI  - Wave-Breaking Extended Coherent Fiber: Supercontinuum Pulse Compression.

PMID- 24587686
TI  - Leptomeningeal carcinomatosis as the initial manifestation of gastric
      adenocarcinoma: a case report.
AB  - Leptomeningeal involvement is usually reported as a secondary event in advanced
      gastric carcinoma. Leptomeningeal carcinomatosis (LMC), as the initial
      manifestation of asymptomatic gastric cancer, is exceedingly rare with only a few
      cases reported in recent years. The presenting neurologic symptoms include
      headache, vomiting and seizures and are usually clinically atypical. The
      diagnosis of LMC is made via identification of malignant cells that originate
      from epithelial cells in the cerebrospinal fluid by cytological examination and
      provides cues to track the primary tumor. Endoscopic examinations are crucial to
      confirm the presence of gastric cancer, and imaging studies, especially
      gadolinium-enhanced magnetic resonance imaging of the brain, are sometimes
      helpful in diagnosis. Thus far, there is no standard therapy for LMC, and despite
      all measures, the prognosis of the condition is extremely poor. Here, we report
      on the clinical features and diagnostic procedures for a patient with occult
      gastric cancer with Bormann type I macroscopic appearance and poor
      differentiation in pathology, who presented with LMC-induced neurological
      symptoms as the initial clinical manifestation. Additionally, we review the
      similar cases reported over the past years, making comparison among cases in
      order to provide more information for the future diagnosis.

PMID- 24587688
TI  - Multicomponent synthesis and anticonvulsant activity of monocyclic 2,6
      diketopiperazine derivatives.
AB  - In this study, a series of diastereomerically pure monocyclic 2,6
      diketopiperazine (2,6-DKP) derivatives were synthesized. The key synthetic step
      involved a multicomponent Ugi five-center, four-component reaction which was used
      to generate the convertible tert-butylamidoesters with both good yields and high
      diastereoselectivity toward the desired bioactive (S,S) absolute configuration.
      In subsequent steps, selective tertbutyl cleavage by use of BF3.CH3COOH and base
      induced intramolecular cyclocondensation gave the final 2,6-DKP derivatives. The
      relative stereochemistry of the target molecules was confirmed by 1H NMR
      experiments. The compounds obtained were submitted to in vivo screening in animal
      models of epilepsy. Some of them displayed good activity in maximal electroshock
      seizure and 6 Hz tests.

PMID- 24587689
TI  - Stimulating Music: The Pleasures and Dangers of "Electric Music," 1750-1900.
AB  - Far from being a purely modern idea, the notion of "electric music" was already
      common in the eighteenth and nineteenth centuries. The shift in thinking about
      music from cosmic harmony to nervous stimulation made metaphors and speculative
      theories relating music and electricity irresistible. This essay considers the
      development of the idea of electric music, looking at its associations with a
      sexual "body electric." It will then examine how this conception of music went
      from being the subject of sympathy to becoming part of a medical critique of
      music as a dangerous stimulant, with echoes in music criticism and beyond.

PMID- 24587690
TI  - Assessing Risks to Sea Otters and the Exxon Valdez Oil Spill: New Scenarios,
      Attributable Risk, and Recovery.
AB  - The Exxon Valdez oil spill occurred more than two decades ago, and the Prince
      William Sound ecosystem has essentially recovered. Nevertheless, discussion
      continues on whether or not localized effects persist on sea otters (Enhydra
      lutris) at northern Knight Island (NKI) and, if so, what are the associated
      attributable risks. A recent study estimated new rates of sea otter encounters
      with subsurface oil residues (SSOR) from the oil spill. We previously
      demonstrated that a potential pathway existed for exposures to polycyclic
      aromatic hydrocarbons (PAHs) and conducted a quantitative ecological risk
      assessment using an individual-based model that simulated this and other
      plausible exposure pathways. Here we quantitatively update the potential for this
      exposure pathway to constitute an ongoing risk to sea otters using the new
      estimates of SSOR encounters. Our conservative model predicted that the
      assimilated doses of PAHs to the 1-in-1000th most-exposed sea otters would remain
      1-2 orders of magnitude below the chronic effects thresholds. We re-examine the
      baseline estimates, post-spill surveys, recovery status, and attributable risks
      for this subpopulation. We conclude that the new estimated frequencies of
      encountering SSOR do not constitute a plausible risk for sea otters at NKI and
      these sea otters have fully recovered from the oil spill.

PMID- 24587691
TI  - Dysfunctional Mitochondrial Dynamics in the Pathophysiology of Neurodegenerative
      Diseases.
AB  - Mitochondrial dysfunction occurs in neurodegenerative diseases, however molecular
      mechanisms underlying this process remain elusive. Emerging evidence suggests
      that nitrosative stress, mediated by reactive nitrogen species (RNS), may play a
      role in mitochondrial pathology. Here, we review findings that highlight the
      abnormal mitochondrial morphology observed in many neurode-generative disorders
      including Alzheimer's, Parkinson's, and Huntington's diseases. One mechanism
      whereby RNS can affect mitochondrial function and thus neuronal survival occurs
      via protein S-nitrosylation, representing chemical reaction of a nitric oxide
      (NO) group with a critical cysteine thiol. In this review, we focus on the
      signaling pathway whereby S-nitrosylation of the mitochondrial fission protein
      Drp1 (dynamin-related protein 1; forming S-nitrosothiol (SNO)-Drp1) precipitates
      excessive mitochondrial fission or fragmentation and consequent bioenergetic
      compromise. Subsequently, the formation of SNO-Drp1 leads to synaptic damage and
      neuronal death. Thus, intervention in the SNO-Drp1 pathway may provide
      therapeutic benefit in neurodegenerative diseases.

PMID- 24587692
TI  - Motion tracking in infrared imaging for quantitative medical diagnostic
      applications.
AB  - In medical applications, infrared (IR) thermography is used to detect and examine
      the thermal signature of skin abnormalities by quantitatively analyzing skin
      temperature in steady state conditions or its evolution over time, captured in an
      image sequence. However, during the image acquisition period, the involuntary
      movements of the patient are unavoidable, and such movements will undermine the
      accuracy of temperature measurement for any particular location on the skin. In
      this study, a tracking approach using a template-based algorithm is proposed, to
      follow the involuntary motion of the subject in the IR image sequence. The motion
      tacking will allow to associate a temperature evolution to each spatial location
      on the body while the body moves relative to the image frame. The affine
      transformation model is adopted to estimate the motion parameters of the template
      image. The Lucas-Kanade algorithm is applied to search for the optimized
      parameters of the affine transformation. A weighting mask is incorporated into
      the algorithm to ensure its tracking robustness. To evaluate the feasibility of
      the tracking approach, two sets of IR image sequences with random in-plane motion
      were tested in our experiments. A steady-state (no heating or cooling) IR image
      sequence in which the skin temperature is in equilibrium with the environment was
      considered first. The thermal recovery IR image sequence, acquired when the skin
      is recovering from 60-s cooling, was the second case analyzed. By proper
      selection of the template image along with template update, satisfactory tracking
      results were obtained for both IR image sequences. The achieved tracking
      accuracies are promising in terms of satisfying the demands imposed by clinical
      applications of IR thermography.

PMID- 24587693
TI  - Orthographic influences on division of labor in learning to read Chinese and
      English: Insights from computational modeling.
AB  - Learning to read any language requires learning to map among print, sound and
      meaning. Writing systems differ in a number of factors that influence both the
      ease and rate with which reading skill can be acquired, as well as the eventual
      division of labor between phonological and semantic processes. Further,
      developmental reading disability manifests differently across writing systems,
      and may be related to different deficits in constitutive processes. Here we
      simulate some aspects of reading acquisition in Chinese and English using the
      same model architecture for both writing systems. The contribution of semantic
      and phonological processing to literacy acquisition in the two languages is
      simulated, including specific effects of phonological and semantic deficits.
      Further, we demonstrate that similar patterns of performance are observed when
      the same model is trained on both Chinese and English as an "early bilingual."
      The results are consistent with the view that reading skill is acquired by the
      application of statistical learning rules to mappings among print, sound and
      meaning, and that differences in the typical and disordered acquisition of
      reading skill between writing systems are driven by differences in the
      statistical patterns of the writing systems themselves, rather than differences
      in cognitive architecture of the learner.

PMID- 24587694
TI  - The ecological basis of morphogenesis: branching patterns in swarming colonies of
      bacteria.
AB  - Understanding how large-scale shapes in tissues, organs and bacterial colonies
      emerge from local interactions among cells and how these shapes remain stable
      over time are two fundamental problems in biology. Here we investigate branching
      morphogenesis in an experimental model system, swarming colonies of the bacterium
      Pseudomonas aeruginosa. We combine experiments and computer simulation to show
      that a simple ecological model of population dispersal can describe the emergence
      of branching patterns. In our system, morphogenesis depends on two counteracting
      processes that act on different length-scales: (1) colony expansion, which
      increases the likelihood of colonizing a patch at a close distance and (2) colony
      repulsion, which decreases the colonization likelihood over a longer distance.
      The two processes are included in a kernel based mathematical model using an
      integro-differential approach borrowed from ecological theory. Computer
      simulations show that the model can indeed reproduce branching, but only for a
      narrow range of parameter values, suggesting that P. aeruginosa has a fine-tuned
      physiology for branching. Simulations further show that hyperswarming, a process
      where highly dispersive mutants reproducibly arise within the colony and disrupt
      branching patterns, can be interpreted as a change in the spatial kernel.

PMID- 24587696
TI  - Jeffery M. Nelson, MD, FACS, FASCRS.

PMID- 24587695
TI  - An Iron(II)(1,3-bis(2'-pyridylimino)isoindoline) Complex as a Catalyst for
      Substrate Oxidation with H2O2. Evidence for a Transient Peroxodiiron(III)
      Species.
AB  - The complex [Fe(indH)(solvent)3](ClO4)2 (1) has been isolated from the reaction
      of equimolar amounts of 1,3-bis(2'-pyridylimino)isoindoline (indH) and Fe(ClO4)2
      in acetonitrile and characterized by X-ray crystallography and several
      spectroscopic techniques. It is a suitable catalyst for the oxidation of
      thioanisoles and benzyl alcohols with H2O2 as the oxidant. Hammett correlations
      and kinetic isotope effect experiments support the involvement of an
      electrophilic metal-based oxidant. A metastable green species (2) is observed
      when 1 is reacted with H2O2 at -40  degrees C, which has been characterized to
      have a FeIII(MU-O)(MU-O2)FeIII core on the basis of UV-Vis, electron paramagnetic
      resonance, resonance Raman, and X-ray absorption spectroscopic data.

PMID- 24587697
TI  - Quality measurement and improvement in colon and rectal surgery.

PMID- 24587698
TI  - History and background of quality measurement.
AB  - Health care quality measurement has become increasingly emphasized, as providers
      and administrators respond to public and government demands for improved patient
      care. This article will review the evolution of surgical quality measurement and
      improvement from its infancy in the 1850s to the vast efforts being undertaken
      today. 

PMID- 24587699
TI  - Current status of quality measurement in colon and rectal surgery.
AB  - There is increasing pressure from the public and insurance payors for
      transparency and accountability in ensuring the quality of health care. In
      response to this, hospitals are now mandated to participate in quality
      improvement initiatives, and to report on their performance. This article
      describes three programs related to the measurement of quality that impact colon
      and rectal surgery: the Surgical Care Improvement Project, the National Surgical
      Quality Improvement Program, and the Surgical Care and Outcomes Assessment
      Program. 

PMID- 24587700
TI  - Participation in quality measurement nationwide.
AB  - In the interest of improving patient care quality and reducing costs, many
      hospitals across the nation participate in quality measurements. The three
      programs most applicable to colon and rectal surgery are the National Surgical
      Quality Improvement Project, the Surgical Care Improvement Project (SCIP), and
      the Surgical Care and Outcomes Assessment Program. Participation in each is
      variable, although many hospitals are eligible and welcome to participate.
      Currently, SCIP is the only one with a financial incentive to participate. This
      article will focus on participation; however, the motivation for such is elusive
      in the literature. It is likely that a combination of resource utilization and
      faith in the concept that participation results in improvements in patient care
      actually drive participation. 

PMID- 24587701
TI  - Controversies surrounding quality measurement in colon and rectal surgery.
AB  - Quality improvement in health care has become a major topic of discussion among
      health care providers, patients, insurance companies, and the government.
      National Surgical Quality Improvement Project (NSQIP), along with a multitude of
      other programs, exists in an attempt to create objective data that can be used to
      compare hospitals and providers against a national average. Studies have shown
      that despite good patient care and proper surgical technique, patients who
      undergo procedures such as colectomy have a higher incidence of surgical site
      infection (SSI) and other morbidities. Therefore, hospitals with a large volume
      of colon and rectal surgery cases are routinely identified as "high outliers" in
      these quality improvement programs. Programs, such as NSQIP, may not be the best
      way to measure quality in specific subspecialties such as colon and rectal
      surgery. 

PMID- 24587702
TI  - The future of quality measurement in the United States.
AB  - The need to practice cost efficient medicine and provide it in the safest way
      possible is paving the way for quality improvement (QI) programs to take off.
      American College of Surgeons National Surgical QI Project and Surgical Care and
      Outcomes Assessment Program are some of the leading examples and have provided
      useful data to evaluate our systems and decrease morbidity and mortality. With
      proven outcomes driving morbidity and mortality rates down, we have to wonder how
      to refine these measures to make them more relevant to specialty surgeries such
      as colorectal. On the contrary, participation in programs like these has placed
      extended requirements on hospitals and physicians. In addition, some of the
      quality measures may be inaccurately identifying low and high performing
      hospitals and individuals because of inherent flaws in the database. This could
      potentially be in conflict with the mission of these programs. What will be
      presented are some alternatives and different directions QI is moving toward. 

PMID- 24587703
TI  - Anomaly monitoring method for key components of satellite.
AB  - This paper presented a fault diagnosis method for key components of satellite,
      called Anomaly Monitoring Method (AMM), which is made up of state estimation
      based on Multivariate State Estimation Techniques (MSET) and anomaly detection
      based on Sequential Probability Ratio Test (SPRT). On the basis of analysis
      failure of lithium-ion batteries (LIBs), we divided the failure of LIBs into
      internal failure, external failure, and thermal runaway and selected electrolyte
      resistance (R(e)) and the charge transfer resistance (R(ct)) as the key
      parameters of state estimation. Then, through the actual in-orbit telemetry data
      of the key parameters of LIBs, we obtained the actual residual value (R(X)) and
      healthy residual value (R(L)) of LIBs based on the state estimation of MSET, and
      then, through the residual values (R(X) and R(L)) of LIBs, we detected the
      anomaly states based on the anomaly detection of SPRT. Lastly, we conducted an
      example of AMM for LIBs, and, according to the results of AMM, we validated the
      feasibility and effectiveness of AMM by comparing it with the results of
      threshold detective method (TDM).

PMID- 24587704
TI  - Carbyne polysulfide as a novel cathode material for rechargeable magnesium
      batteries.
AB  - We report the formation of carbyne polysulfide by coheating carbon containing
      carbyne moieties and elemental sulfur. The product is proved to have a sp2 hybrid
      carbon skeleton with polysulfide attached on it. The electrochemical performance
      of carbyne polysulfide as a novel cathode material for rechargeable magnesium
      batteries is firstly investigated. The material exhibits a high discharge
      capacity of 327.7 mAh g(-1) at 3.9 mA g(-1). These studies show that carbyne
      polysulfide is a promising candidate as cathode material for rechargeable Mg
      batteries if the capacity retention can be significantly improved.

PMID- 24587705
TI  - C-reactive protein and cognition are unrelated to leukoaraiosis.
AB  - Elevated serum levels of C-reactive protein (CRP) have been associated with
      leukoaraiosis in elderly brain. However, several studies indicate that
      leukoaraiosis is associated with an increased risk of cognitive impairment. It is
      unknown how the effect of CRP on cognition is mediated by leukoaraiosis. The
      purpose of this study is to assess the relationship between serum levels of CRP,
      the presence of leukoaraiosis, and cognitive impairment in a population of
      coronary patients over 50 years old. CRP levels explained 7.18% (P: 0.002) of the
      variance of the MMSE. The adjustment for the presence of leukoaraiosis little
      changed this variance (5.98%, P: 0.005), indicating that only a small portion of
      the CRP influence on cognition was mediated via leukoaraiosis. Patients with CRP
      levels >= 5.0 had 2.9 (95% CI: 1.26-6.44) times more chance to present cognitive
      impairment (P: 0.012). We found that elevated serum levels of CRP were associated
      with increased risk of cognitive impairment in elderly and it was not mediated by
      presence of leukoaraiosis.

PMID- 24587706
TI  - Comparison of the chromosome banding pattern in the 2n = 56 cytotypes of
      Nannospalax leucodon and N. xanthodon from Turkey.
AB  - We present the karyotype characteristics of five cytotypes of mole rats
      (Nannospalax) with 56 chromosomes revealed by the C-banding and AgNOR staining
      analyses. We attempt to investigate if the specific distinction between the
      populations from Thrace (N. leucodon) and Anatolia (N. xanthodon) is reflected
      also in their karyotypic differentiation. The specimens from each of the five
      populations studied revealed a distinct karyotype which was different from those
      found in other populations. The fundamental number of autosomal arms varied from
      68 to 72. The amount of C-heterochromatin was larger in the Thrace sample of N.
      leucodon compared to the Anatolian population of N. xanthodon. The active NOR
      sites were recorded on five autosomal pairs in N. leucodon, whereas only three or
      four pairs bearing NOR were observed in N. xanthodon. Differences between the
      studied populations were quantified in the analysis of the distribution pattern
      of the C-positive bands and the AgNOR sites in individual chromosomes which
      indicated a basal position of the Thrace sample of N. leucodon and its divergence
      from other studied populations. The karyotypes of the 56-chromosome populations
      of N. leucodon and N. xanthodon are thus distinctly different. 

PMID- 24587708
TI  - Response of nitrogen and potassium fertigation to "Waris" almond (Prunus dulcis)
      under northwestern Himalayan Region of India.
AB  - A field experiment was conducted on almond (Prunus dulcis) to study the effect of
      N&K fertigation on growth, yields and leaf nutrient status over two seasons (2011
      and 2012) in Srinagar, Jammu and Kashmir, India. There were six treatments,
      namely, T1--100% recommended dose of fertilizers as soil application, T2--100%
      RDF through fertigations, T3--75% RDF through fertigation, T4--75% RDF through
      fertigation (split application), T5--50% RDF through fertigation and T6--50% RDF
      through fertigation (split application) with three replications under randomized
      block design. The results indicated that the maximum tree height (3.21 m and 3.56
      m), nut weight (2.73 g and 1.94 g), nut yield (2.41 kg/tree and 5.98 kg/tree;
      2.67 t/ha and 6.64 t/ha), and leaf nutrient content (2.34 and 2.38% N; 0.14 and
      0.17% P; 1.37 and 1.41% K) were recorded in T4 treatment, whereas the highest
      TCSA of main trunk, primary, secondary, and tertiary branches (72.67 and 90.28
      cm(2); 16.75 and 24.26 cm(2); 3.83 and 7.49 cm(2); 0.47 and 1.23 cm(2)), canopy
      volume (7.15 and 8.11 m(3)), and fruit number (990 and 3083/tree) were recorded
      in T2 in almond variety Waris.

PMID- 24587707
TI  - Prognostic value of C-reactive protein, leukocytes, and vitamin d in severe
      chronic obstructive pulmonary disease.
AB  - Inflammatory biomarkers predict mortality and hospitalisation in chronic
      obstructive pulmonary disease (COPD). Yet, it remains uncertain if biomarkers in
      addition to reflecting disease severity add new prognostic information on severe
      COPD. We investigated if leukocytes, C-reactive protein (CRP), and vitamin D were
      independent predictors of mortality and hospitalisation after adjusting for
      disease severity with an integrative index, the i-BODE index. In total, 423
      patients participating in a pulmonary rehabilitation programme, with a mean value
      of FEV1 of 38% of predicted, were included. Mean followup was 45 months. During
      the follow-up period, 149 deaths (35%) were observed and 330 patients (78.0%) had
      at least one acute hospitalisation; 244 patients (57.7%) had at least one
      hospitalisation due to an exacerbation of COPD. In the analysis (Cox proportional
      hazards model) fully adjusted for age, sex, and i-BODE index, the hazard ratio
      for 1 mg/L increase in CRP was 1.02 (P=0.003) and for 1*10(9)/L increase in
      leukocytes was 1.43 (P=0.03). Only leukocyte count was significantly associated
      with hospitalisation. Vitamin D was neither associated with mortality nor
      hospitalisation. Leukocytes and CRP add little information on prognosis and
      vitamin D does not seem to be a useful biomarker in severe COPD in a clinical
      setting.

PMID- 24587709
TI  - Use of Landsat land surface temperature and vegetation indices for monitoring
      drought in the Salt Lake Basin Area, Turkey.
AB  - The main purpose of this paper is to investigate multitemporal land surface
      temperature (LST) changes by using satellite remote sensing data. The study
      included a real-time field work performed during the overpass of Landsat-5
      satellite on 21/08/2011 over Salt Lake, Turkey. Normalized vegetation index
      (NDVI), vegetation condition index (VCI), and temperature vegetation index (TVX)
      were used for evaluating drought impact over the region between 1984 and 2011. In
      the image processing step, geometric and radiometric correction procedures were
      conducted to make satellite remote sensing data comparable with in situ
      measurements carried out using thermal infrared thermometer supported by hand
      held GPS. The results showed that real-time ground and satellite remote sensing
      data were in good agreement with correlation coefficient (R2) values of 0.90. The
      remotely sensed and treated satellite images and resulting thematic indices maps
      showed that dramatic land surface temperature changes occurred (about 2 degrees
      C) in the Salt Lake Basin area during the 28-year period (1984-2011). Analysis of
      air temperature data also showed increases at a rate of 1.5-2 degrees C during
      the same period. Intensification of irrigated agriculture particularly in the
      southern basin was also detected. The use of water supplies, especially
      groundwater, should be controlled considering particularly summer drought impacts
      on the basin.

PMID- 24587710
TI  - Noncovalent interactions of tiopronin-protected gold nanoparticles with DNA: two
      methods to quantify free energy of binding.
AB  - The binding of gold nanoparticles capped with N-(2-mercaptopropionyl)glycine
      (Au@tiopronin) with double-stranded DNA has been investigated and quantified in
      terms of free energies by using two different approaches. The first approach
      follows the DNA conformational changes induced by gold nanoparticles using the CD
      technique. The second methodology consists in the use of pyrene-1-carboxaldehyde
      as a fluorescent probe. This second procedure implies the determination of the
      "true" free energy of binding of the probe with DNA, after corrections through
      solubility measurements. Working at different salt concentrations, the
      nonelectrostatic and electrostatic components of the binding free energy have
      been separated. The results obtained revealed that the binding is of
      nonelectrostatic character, fundamentally. The procedure used in this work could
      be extended to quantify the binding affinity of other AuNPs/DNA systems. 

PMID- 24587711
TI  - Improved BDF relaying scheme using time diversity over atmospheric turbulence and
      misalignment fading channels.
AB  - A novel bit-detect-and-forward (BDF) relaying scheme based on repetition coding
      with the relay is proposed, significantly improving the robustness to impairments
      proper to free-space optical (FSO) communications such as unsuitable alignment
      between transmitter and receiver as well as fluctuations in the irradiance of the
      transmitted optical beam due to the atmospheric turbulence. Closed-form
      asymptotic bit-error-rate (BER) expressions are derived for a 3-way FSO
      communication setup. Fully exploiting the potential time-diversity available in
      the relay turbulent channel, a relevant better performance is achieved, showing a
      greater robustness to the relay location since a high diversity gain is provided
      regardless of the source-destination link distance. 

PMID- 24587712
TI  - Vocal emotion of humanoid robots: a study from brain mechanism.
AB  - Driven by rapid ongoing advances in humanoid robot, increasing attention has been
      shifted into the issue of emotion intelligence of AI robots to facilitate the
      communication between man-machines and human beings, especially for the vocal
      emotion in interactive system of future humanoid robots. This paper explored the
      brain mechanism of vocal emotion by studying previous researches and developed an
      experiment to observe the brain response by fMRI, to analyze vocal emotion of
      human beings. Findings in this paper provided a new approach to design and
      evaluate the vocal emotion of humanoid robots based on brain mechanism of human
      beings. 

PMID- 24587713
TI  - Tunable first-order resistorless all-pass filter with low output impedance.
AB  - This paper presents a voltage mode cascadable single active element tunable first
      order all-pass filter with a single passive component. The active element used to
      realise the filter is a new building block termed as differential difference dual
      X current conveyor with a buffered output (DD-DXCCII). The filter is thus
      realized with the help of a DD-DXCCII, a capacitor, and a MOS transistor. By
      exploiting the low output impedance, a higher order filter is also realized.
      Nonideal and parasitic study is also carried out on the realised filters. The
      proposed DD-DXCCII filters are simulated using TSMC the 0.25 um technology.

PMID- 24587714
TI  - A stochastic restricted principal components regression estimator in the linear
      model.
AB  - We propose a new estimator to combat the multicollinearity in the linear model
      when there are stochastic linear restrictions on the regression coefficients. The
      new estimator is constructed by combining the ordinary mixed estimator (OME) and
      the principal components regression (PCR) estimator, which is called the
      stochastic restricted principal components (SRPC) regression estimator. Necessary
      and sufficient conditions for the superiority of the SRPC estimator over the OME
      and the PCR estimator are derived in the sense of the mean squared error matrix
      criterion. Finally, we give a numerical example and a Monte Carlo study to
      illustrate the performance of the proposed estimator. 

PMID- 24587715
TI  - Impact of endophytic microorganisms on plants, environment and humans.
AB  - Endophytes are microorganisms (bacteria or fungi or actinomycetes) that dwell
      within robust plant tissues by having a symbiotic association. They are
      ubiquitously associated with almost all plants studied till date. Some commonly
      found endophytes are those belonging to the genera Enterobacter sp.,
      Colletotrichum sp., Phomopsis sp., Phyllosticta sp., Cladosporium sp., and so
      forth. Endophytic population is greatly affected by climatic conditions and
      location where the host plant grows. They produce a wide range of compounds
      useful for plants for their growth, protection to environmental conditions, and
      sustainability, in favour of a good dwelling place within the hosts. They protect
      plants from herbivory by producing certain compounds which will prevent animals
      from further grazing on the same plant and sometimes act as biocontrol agents. A
      large amount of bioactive compounds produced by them not only are useful for
      plants but also are of economical importance to humans. They serve as
      antibiotics, drugs or medicines, or the compounds of high relevance in research
      or as compounds useful to food industry. They are also found to have some
      important role in nutrient cycling, biodegradation, and bioremediation. In this
      review, we have tried to comprehend different roles of endophytes in plants and
      their significance and impacts on man and environment. 

PMID- 24587716
TI  - Growth of ZnO nanorods on stainless steel wire using chemical vapour deposition
      and their photocatalytic activity.
AB  - The photodegradation efficiency of ZnO nanoparticles in removal of organic
      pollutants deteriorates over time as a high percentage of the nanoparticles can
      be drained away by water during the wastewater treatment. This problem can be
      solved by growing the ZnO nanorods on stainless steel wire. In this work, ZnO
      nanorods were successfully grown on stainless steel wire by chemical vapour
      deposition. The SAED analysis indicates that ZnO nanorod is a single crystal and
      is preferentially grown in [0001] direction. The deconvoluted O 1s peak at 531.5
      eV in XPS analysis is associated with oxygen deficient, revealing that the ZnO
      nanorods contain many oxygen vacancies. This observation is further supported by
      the finding of the small I(uv)/I(vis) ratio, that is, ~1 in the photoluminescence
      analysis. The growth of ZnO nanorods on stainless steel wire was governed by
      vapour-solid mechanism as there were no Fe particles observed at the tips of the
      nanorods. The photodegradation of Rhodamine B solution by ZnO nanorods followed
      the first-order kinetics.

PMID- 24587717
TI  - Production of prodigiosin using tannery fleshing and evaluating its
      pharmacological effects.
AB  - AIM: The focal theme of present investigation includes isolation of prodigiosin
      producing fish gut bacteria, enhancing its production using tannery solid waste
      fleshing, and evaluation of its pharmacological effect. METHODS: Optimization of
      fermentation conditions to yield maximum prodigiosin, and instrumental analysis
      using FTIR, NMR, ESI-MS, TGA, and DSC. RESULTS: The optimum conditions required
      for the maximum prodigiosin concentration were achieved at time 30 h, temperature
      30 degrees C, pH 8, and 3% substrate concentration. The secondary metabolite was
      analyzed using ESI-MS, FTIR, and NMR. Therapeutic efficacy was assessed by in
      vitro anticancer studies. Among the pathogenic bacteria Pseudomonas aeruginosa
      was most susceptible at the lowest concentration followed by Salmonella typhi.
      IC50 concentration was cell line specific (HeLa cells: 4.3 uM, HEp2: 5.2 uM, and
      KB cells: 4.8 uM) and remains nontoxic up to the concentration of 25 uM on normal
      Vero cells suggesting that cancerous cells are more susceptible to the
      prodigiosin at lower concentration. CONCLUSION: Maximum prodigiosin production
      was obtained with tannery fleshing. The potency of the fish gut bacterial
      secondary metabolite prodigiosin as a therapeutic agent was confirmed through in
      vitro antimicrobial and anticancer studies.

PMID- 24587718
TI  - The potential for dams to impact lowland meandering river floodplain
      geomorphology.
AB  - The majority of the world's floodplains are dammed. Although some implications of
      dams for riverine ecology and for river channel morphology are well understood,
      there is less research on the impacts of dams on floodplain geomorphology. We
      review studies from dammed and undammed rivers and include influences on vertical
      and lateral accretion, meander migration and cutoff formation, avulsion, and
      interactions with floodplain vegetation. The results are synthesized into a
      conceptual model of the effects of dams on the major geomorphic influences on
      floodplain development. This model is used to assess the likely consequences of
      eight dam and flow regulation scenarios for floodplain geomorphology. Sediment
      starvation downstream of dams has perhaps the greatest potential to impact on
      floodplain development. Such effects will persist further downstream where
      tributary sediment inputs are relatively low and there is minimal buffering by
      alluvial sediment stores. We can identify several ways in which floodplains might
      potentially be affected by dams, with varying degrees of confidence, including a
      distinction between passive impacts (floodplain disconnection) and active impacts
      (changes in geomorphological processes and functioning). These active processes
      are likely to have more serious implications for floodplain function and
      emphasize both the need for future research and the need for an "environmental
      sediment regime" to operate alongside environmental flows. 

PMID- 24587719
TI  - Network-aware HEFT scheduling for grid.
AB  - We present a network-aware HEFT. The original HEFT does not take care of parallel
      network flows while designing its schedule for a computational environment where
      computing nodes are physically at distant locations. In the proposed mechanism,
      such data transfers are stretched to their realistic completion time. A HEFT
      schedule with stretched data transfers exhibits the realistic makespan of the
      schedule. It is shown how misleading a schedule can be if the impact of parallel
      data transfers that share a bottleneck is ignored. A network-aware HEFT can be
      used to yield a benefit for Grid applications. 

PMID- 24587720
TI  - Thermal behaviour of beams with slant end-plate connection subjected to
      nonsymmetric gravity load.
AB  - Research on the steel structures with confining of axial expansion in fixed beams
      has been quite intensive in the past decade. It is well established that the
      thermal behaviour has a key influence on steel structural behaviours. This paper
      describes mechanical behaviour of beams with bolted slant end-plate connection
      with nonsymmetric gravity load, subjected to temperature increase. Furthermore,
      the performance of slant connections of beams in steel moment frame structures in
      the elastic field is investigated. The proposed model proved that this flexible
      connection system could successfully decrease the extra thermal induced axial
      force by both of the friction force dissipation among two faces of slant
      connection and a small upward movement on the slant plane. The applicability of
      primary assumption is illustrated. The results from the proposed model are
      examined within various slant angles, thermal and friction factors. It can be
      concluded that higher thermal conditions are tolerable when slanting connection
      is used. 

PMID- 24587721
TI  - The modification of polyurethane foams using new boroorganic polyols (II)
      polyurethane foams from boron-modified hydroxypropyl urea derivatives.
AB  - The work focuses on research related to determination of application possibility
      of new, ecofriendly boroorganic polyols in rigid polyurethane foams production.
      Polyols were obtained from hydroxypropyl urea derivatives esterified with boric
      acid and propylene carbonate. The influence of esterification type on properties
      of polyols and next on polyurethane foams properties was determined. Nitrogen and
      boron impacts on the foams' properties were discussed, for instance, on their
      physical, mechanical, and electric properties. Boron presence causes improvement
      of dimensional stability and thermal stability of polyurethane foams. They can be
      applied even at temperature 150  degrees C. Unfortunately, introducing boron in
      polyurethanes foams affects deterioration of their water absorption, which
      increases as compared to the foams that do not contain boron. However, presence
      of both boron and nitrogen determines the decrease of the foams combustibility.
      Main impact on the decrease combustibility of the obtained foams has nitrogen
      presence, but in case of proper boron and nitrogen ratio their synergic activity
      on the combustibility decrease can be easily seen.

PMID- 24587722
TI  - Preparation and characterization of chitosan/feldspar biohybrid as an adsorbent:
      optimization of adsorption process via response surface modeling.
AB  - Chitosan/feldspar biobased beads were synthesized, characterized, and tested for
      the removal of Acid Black 1 dye from aquatic phases. A four-factor central
      composite design (CCD) accompanied by response surface modeling (RSM) and
      optimization was used to optimize the dye adsorption by the adsorbent
      (chitosan/feldspar composite) in 31 different batch experiments. Independent
      variables of temperature, pH, initial dye concentration, and adsorbent dose were
      used to change to coded values. To anticipate the responses, a quadratic model
      was applied. Analysis of variance (ANOVA) tested the significance of the process
      factors and their interactions. The adequacy of the model was investigated by the
      correlation between experimental and predicted data of the adsorption and the
      calculation of prediction errors. The results showed that the predicted maximum
      adsorption amount of 21.63 mg/g under the optimum conditions (pH 3, temperature
      15 degrees C, initial dye concentration 125 mg/L, and dose 0.2 g/50 mL) was close
      to the experimental value of 19.85 mg/g. In addition, the results of adsorption
      behaviors of the dye illustrated that the adsorption process followed the
      Langmuir isotherm model and the pseudo-second-order kinetic model. Langmuir
      sorption capacity was found to be 17.86 mg/g. Besides, thermodynamic parameters
      were evaluated and revealed that the adsorption process was exothermic and
      favourable. 

PMID- 24587723
TI  - Toluene removal from sandy soils via in situ technologies with an emphasis on
      factors influencing soil vapor extraction.
AB  - The integration of bioventing (BV) and soil vapor extraction (SVE) appears to be
      an effective combination method for soil decontamination. This paper serves two
      main purposes: it evaluates the effects of soil water content (SWC) and air flow
      rate on SVE and it investigates the transition regime between BV and SVE for
      toluene removal from sandy soils. 96 hours after air injection, more than 97%
      removal efficiency was achieved in all five experiments (carried out for SVE)
      including 5, 10, and 15% for SWC and 250 and 500 mL/min for air flow rate on SVE.
      The highest removal efficiency (>99.5%) of toluene was obtained by the
      combination of BV and SVE (AIBV: Air Injection Bioventing) after 96 h of air
      injection at a constant flow rate of 250 mL/min. It was found that AIBV has the
      highest efficiency for toluene removal from sandy soils and can remediate the
      vadose zone effectively to meet the soil guideline values for protection of
      groundwater. 

PMID- 24587724
TI  - Influence of the feed moisture, rotor speed, and blades gap on the performances
      of a biomass pulverization technology.
AB  - Recently, a novel biomass pulverization technology was proposed by our group. In
      this paper, further detailed studies of this technology were carried out. The
      effects of feed moisture and crusher operational parameters (rotor speed and
      blades gap) on product particle size distribution and energy consumption were
      investigated. The results showed that higher rotor speed and smaller blades gap
      could improve the hit probability between blades and materials and enhance the
      impacting and grinding effects to generate finer products, however, resulting in
      the increase of energy consumption. Under dry conditions finer particles were
      much more easily achieved, and there was a tendency for the specific energy to
      increase with increasing feed moisture. Therefore, it is necessary for the raw
      biomass material to be dried before pulverization. 

PMID- 24587725
TI  - Validation of simultaneous quantitative method of HIV protease inhibitors
      atazanavir, darunavir and ritonavir in human plasma by UPLC-MS/MS.
AB  - OBJECTIVES: HIV protease inhibitors are used in the treatment of patients
      suffering from AIDS and they act at the final stage of viral replication by
      interfering with the HIV protease enzyme. The paper describes a selective,
      sensitive, and robust method for simultaneous determination of three protease
      inhibitors atazanavir, darunavir and ritonavir in human plasma by ultra
      performance liquid chromatography-tandem mass spectrometry. MATERIALS AND
      METHODS: The sample pretreatment consisted of solid phase extraction of analytes
      and their deuterated analogs as internal standards from 50 MUL human plasma.
      Chromatographic separation of analytes was performed on Waters Acquity UPLC C18
      (50 * 2.1 mm, 1.7 MUm) column under gradient conditions using 10 mM ammonium
      formate, pH 4.0, and acetonitrile as the mobile phase. RESULTS: The method was
      established over a concentration range of 5.0-6000 ng/mL for atazanavir, 5.0-5000
      ng/mL for darunavir and 1.0-500 ng/mL for ritonavir. Accuracy, precision, matrix
      effect, recovery, and stability of the analytes were evaluated as per US FDA
      guidelines. CONCLUSIONS: The efficiency of sample preparation, short analysis
      time, and high selectivity permit simultaneous estimation of these inhibitors.
      The validated method can be useful in determining plasma concentration of these
      protease inhibitors for therapeutic drug monitoring and in high throughput
      clinical studies.

PMID- 24587726
TI  - Using data crawlers and semantic Web to build financial XBRL data generators: the
      SONAR extension approach.
AB  - Precise, reliable and real-time financial information is critical for added-value
      financial services after the economic turmoil from which markets are still
      struggling to recover. Since the Web has become the most significant data source,
      intelligent crawlers based on Semantic Technologies have become trailblazers in
      the search of knowledge combining natural language processing and ontology
      engineering techniques. In this paper, we present the SONAR extension approach,
      which will leverage the potential of knowledge representation by extracting,
      managing, and turning scarce and disperse financial information into well
      classified, structured, and widely used XBRL format-oriented knowledge, strongly
      supported by a proof-of-concept implementation and a thorough evaluation of the
      benefits of the approach. 

PMID- 24587727
TI  - A new automated way to measure polyethylene wear in THA using a high resolution
      CT scanner: method and analysis.
AB  - As the most advantageous total hip arthroplasty (THA) operation is the first,
      timely replacement of only the liner is socially and economically important
      because the utilization of THA is increasing as younger and more active patients
      are receiving implants and they are living longer. Automatic algorithms were
      developed to infer liner wear by estimating the separation between the acetabular
      cup and femoral component head given a computed tomography (CT) volume. Two
      series of CT volumes of a hip phantom were acquired with the femoral component
      head placed at 14 different positions relative to the acetabular cup. The mean
      and standard deviation (SD) of the diameter of the acetabular cup and femoral
      component head, in addition to the range of error in the expected wear values and
      the repeatability of all the measurements, were calculated. The algorithms
      resulted in a mean (+/- SD) for the diameter of the acetabular cup of 54.21 (+/-
      0.011) mm and for the femoral component head of 22.09 (+/- 0.02) mm. The wear
      error was +/- 0.1 mm and the repeatability was 0.077 mm. This approach is
      applicable clinically as it utilizes readily available computed tomography
      imaging systems and requires only five minutes of human interaction.

PMID- 24587728
TI  - Some inequalities for the q-analogue of the classical Riemann zeta functions and
      the q-polygamma functions.
AB  - We present the generalizations on some inequalities for the q-analogue of the
      classical Riemann zeta functions and the q-polygamma functions. 

PMID- 24587729
TI  - Effects of herbal essential oil mixture as a dietary supplement on egg production
      in quail.
AB  - One hundred and eighty 7-week-old laying quail were fed various diets over a 12
      week period. The diets included a control diet (without essential oil mixture
      (EOM) or antibiotics (ANTs)), a basal diet including EOM (24 mg/kg feed), and a
      basal diet including an ANT (avilamycin, 10 mg/kg feed). Each treatment comprised
      4 replications with 4 cages (15 quail per cage), amounting to 60 quail per
      treatment group. Diets (in mash form) and water were provided for ad libitum
      consumption. EOM consisted of 6 different essential oils derived from the
      following herbs: oregano (Origanum sp.), laurel leaf (Laurus nobilis L.), sage
      leaf (Salvia triloba L.), myrtle leaf (Myrtus communis), fennel seeds (Foeniculum
      vulgare), and citrus peel (Citrus sp.). In comparison with the control diet,
      adding supplements such as EOM and ANTs to the basal diet increased egg
      production in quail (P < 0.001). However, egg production was similar between EOM
      and ANT treatment groups. Moreover, there were no differences between the
      treatment groups with regard to egg weight. Feed intake was not affected by EOM
      or ANT supplementation, whereas feed conversion ratio was significantly improved
      by EOM and ANT supplementation. Thus, we concluded that EOM has beneficial
      effects as a dietary supplement on egg production and feed conversion ratio. 

PMID- 24587730
TI  - Sperm cryopreservation before testicular cancer treatment and its subsequent
      utilization for the treatment of infertility.
AB  - AIMS: In this study we report our results with storage of cryopreserved semen
      intended for preservation and subsequent infertility treatment in men with
      testicular cancer during the last 18 years. METHODS: Cryopreserved semen of 523
      men with testicular cancer was collected between October 1995 and the end of
      December 2012. Semen of 34 men (6.5%) was used for fertilization of their
      partners. They underwent 57 treatment cycles with cryopreserved, fresh, and/or
      donor sperm. RESULTS: A total of 557 men have decided to freeze their semen
      before cancer treatment. Azoospermia was diagnosed in 34 men (6.1%), and semen
      was cryopreserved in 532 patients. Seminoma was diagnosed in 283 men (54.1%) and
      nonseminomatous germ cell tumors in 240 men (45.9%). 34 patients who returned for
      infertility treatment underwent 46 treatment cycles with cryopreserved sperm.
      Totally 16 pregnancies were achieved, that is, 34.8% pregnancy rate. CONCLUSION:
      The testicular cancer survivors have a good chance of fathering a child by using
      sperm cryopreserved prior to the oncology treatment, even when it contains only
      limited number of spermatozoa.

PMID- 24587731
TI  - Designing a ring-VCO for RFID transponders in 0.18 MUm CMOS process.
AB  - In radio frequency identification (RFID) systems, performance degradation of
      phase locked loops (PLLs) mainly occurs due to high phase noise of voltage
      controlled oscillators (VCOs). This paper proposes a low power, low phase noise
      ring-VCO developed for 2.42 GHz operated active RFID transponders compatible with
      IEEE 802.11 b/g, Bluetooth, and Zigbee protocols. For ease of integration and
      implementation of the module in tiny die area, a novel pseudodifferential delay
      cell based 3-stage ring oscillator has been introduced to fabricate the ring-VCO.
      In CMOS technology, 0.18 MUm process is adopted for designing the circuit with
      1.5 V power supply. The postlayout simulated results show that the proposed
      oscillator works in the tuning range of 0.5-2.54 GHz and dissipates 2.47 mW of
      power. It exhibits a phase noise of -126.62 dBc/Hz at 25 MHz offset from 2.42 GHz
      carrier frequency.

PMID- 24587732
TI  - Dengue outbreak in a hilly state of Arunachal Pradesh in Northeast India.
AB  - Dengue has been reported from plains as well as hilly regions of India including
      some parts of Northeast India. In July-August 2012, outbreak of fever with
      unknown origin (FUO) indicative of Dengue was reported in Pasighat, East Siang
      district of Arunachal Pradesh (AP) state. Serum samples (n = 164) collected from
      patients from Health Training and Research Centre General Hospital, Pasighat,
      were tested for NS1 antigen and IgM antibodies. NS1-positive samples were
      analyzed by RT-PCR assay and entomological surveys were carried out. The majority
      of suspected cases reported NS1 antigen positivity. Females and young adults were
      mostly affected. The majority of the amplified NS1-positive samples showed Dengue
      serotype 3 infection. Aedes (Stegomyia) albopictus, known as semiurban breeding
      mosquitoes, was the only potential vector species identified from the affected
      areas of Pasighat which single handedly contributed to the outbreak. Thus, the
      present work identifies Dengue as an emerging arboviral infection in hilly state
      of AP along with a looming risk of its spread to neighbouring areas. 

PMID- 24587733
TI  - Effect of probiotics supplementation on bone mineral content and bone mass
      density.
AB  - A few studies in animals and a study in humans showed a positive effect of
      probiotic on bone metabolism and bone mass density. Most of the investigated
      bacteria were Lactobacillus and Bifidobacterium. The positive results of the
      probiotics were supported by the high content of dietary calcium and the high
      amounts of supplemented probiotics. Some of the principal mechanisms include (1)
      increasing mineral solubility due to production of short chain fatty acids; (2)
      producing phytase enzyme by bacteria to overcome the effect of mineral depressed
      by phytate; (3) reducing intestinal inflammation followed by increasing bone mass
      density; (4) hydrolysing glycoside bond food in the intestines by Lactobacillus
      and Bifidobacteria. These mechanisms lead to increase bioavailability of the
      minerals. In conclusion, probiotics showed potential effects on bone metabolism
      through different mechanisms with outstanding results in the animal model. The
      results also showed that postmenopausal women who suffered from low bone mass
      density are potential targets to consume probiotics for increasing mineral
      bioavailability including calcium and consequently increasing bone mass density.

PMID- 24587734
TI  - Integrating energy and environmental management in wood furniture industry.
AB  - As energy costs continue to rise, industrial plants (even those of energy
      nonintensive industries such as furniture industry) need effective way to reduce
      the amount of energy they consume. Besides, there are a number of economic and
      environmental reasons why a company should consider environmental management
      initiatives. This paper provides a detailed guideline for implementing joint
      energy and environmental management system in wood furniture industrial company.
      It covers in detail all essential aspects of the system: initial system
      assessment, organization, policy development, energy and environmental auditing,
      action plan development, system promotion, checking system performance, and
      management review. 

PMID- 24587735
TI  - Modelling socio-environmental sensitivities: how public responses to low carbon
      energy technologies could shape the UK energy system.
AB  - Low carbon energy technologies are not deployed in a social vacuum; there are a
      variety of complex ways in which people understand and engage with these
      technologies and the changing energy system overall. However, the role of the
      public's socio-environmental sensitivities to low carbon energy technologies and
      their responses to energy deployments does not receive much serious attention in
      planning decarbonisation pathways to 2050. Resistance to certain resources and
      technologies based on particular socio-environmental sensitivities would alter
      the portfolio of options available which could shape how the energy system
      achieves decarbonisation (the decarbonisation pathway) as well as affecting the
      cost and achievability of decarbonisation. Thus, this paper presents a series of
      three modelled scenarios which illustrate the way that a variety of socio
      environmental sensitivities could impact the development of the energy system and
      the decarbonisation pathway. The scenarios represent risk aversion (DREAD) which
      avoids deployment of potentially unsafe large-scale technology, local
      protectionism (NIMBY) that constrains systems to their existing spatial
      footprint, and environmental awareness (ECO) where protection of natural
      resources is paramount. Very different solutions for all three sets of
      constraints are identified; some seem slightly implausible (DREAD) and all show
      increased cost (especially in ECO). 

PMID- 24587736
TI  - Blood transfusions in total hip and knee arthroplasty: an analysis of outcomes.
AB  - BACKGROUND: Various studies have raised concern of worse outcomes in patients
      receiving blood transfusions perioperatively compared to those who do not. In
      this study we attempted to determine the proportion of perioperative
      complications in the orthopedic population attributable to the use of a blood
      transfusion. METHODS: Data from 400 hospitals in the United States were used to
      identify patients undergoing total hip or knee arthroplasty (THA and TKA) from
      2006 to 2010. Patient and health care demographics, as well as comorbidities and
      perioperative outcomes were compared. Multivariable logistic regression models
      were fitted to determine associations between transfusion, age, and comorbidities
      and various perioperative outcomes. Population attributable fraction (PAF) was
      determined to measure the proportion of outcome attributable to transfusion and
      other risk factors. RESULTS: Of 530,089 patients, 18.93% received a blood
      transfusion during their hospitalization. Patients requiring blood transfusion
      were significantly older and showed a higher comorbidity burden. In addition,
      these patients had significantly higher rates of major complications and a longer
      length of hospitalization. The logistic regression models showed that transfused
      patients were more likely to have adverse health outcomes than nontransfused
      patients. However, patients who were older or had preexisting diseases carried a
      higher risk than use of a transfusion for these outcomes. The need for a blood
      transfusion explained 9.51% (95% CI 9.12-9.90) of all major complications.
      CONCLUSIONS: Advanced age and high comorbidity may be responsible for a higher
      proportion of adverse outcomes in THA and TKA patients than blood transfusions.

PMID- 24587737
TI  - Effects of blended-cement paste chemical composition changes on some strength
      gains of blended-mortars.
AB  - Effects of chemical compositions changes of blended-cement pastes (BCPCCC) on
      some strength gains of blended cement mortars (BCMSG) were monitored in order to
      gain a better understanding for developments of hydration and strength of blended
      cements. Blended cements (BC) were prepared by blending of 5% gypsum and 6%, 20%,
      21%, and 35% marble powder (MP) or 6%, 20%, 21%, and 35% brick powder (BP) for
      CEMI42.5N cement clinker and grinding these portions in ball mill at 30 (min).
      Pastes and mortars, containing the MP-BC and the BP-BC and the reference cement
      (RC) and tap water and standard mortar sand, were also mixed and they were cured
      within water until testing. Experiments included chemical compositions of pastes
      and compressive strengths (CS) and flexural strengths (FS) of mortars were
      determined at 7th-day, 28th-day, and 90th-day according to TS EN 196-2 and TS EN
      196-1 present standards. Experimental results indicated that ups and downs of
      silica oxide (SiO2), sodium oxide (Na2O), and alkali at MP-BCPCC and continuously
      rising movement of silica oxide (SiO2) at BP-BCPCC positively influenced CS and
      FS of blended cement mortars (BCM) in comparison with reference mortars (RM) at
      whole cure days as MP up to 6% or BP up to 35% was blended for cement. 

PMID- 24587738
TI  - Voice quality modelling for expressive speech synthesis.
AB  - This paper presents the perceptual experiments that were carried out in order to
      validate the methodology of transforming expressive speech styles using voice
      quality (VoQ) parameters modelling, along with the well-known prosody (F 0,
      duration, and energy), from a neutral style into a number of expressive ones. The
      main goal was to validate the usefulness of VoQ in the enhancement of expressive
      synthetic speech in terms of speech quality and style identification. A harmonic
      plus noise model (HNM) was used to modify VoQ and prosodic parameters that were
      extracted from an expressive speech corpus. Perception test results indicated the
      improvement of obtained expressive speech styles using VoQ modelling along with
      prosodic characteristics. 

PMID- 24587739
TI  - Topologies on superspaces of TVS-cone metric spaces.
AB  - This paper investigates superspaces ??0(X) and ??0(X) of a tvs-cone metric space
      (X, d), where ??0(X) and ??0(X) are the space consisting of nonempty subsets of X
      and the space consisting of nonempty compact subsets of X, respectively. The
      purpose of this paper is to establish some relationships between the lower
      topology and the lower tvs-cone hemimetric topology (resp., the upper topology
      and the upper tvs-cone hemimetric topology to the Vietoris topology and the
      Hausdorff tvs-cone hemimetric topology) on ??0(X) and ??0(X), which makes it
      possible to generalize some results of superspaces from metric spaces to tvs-cone
      metric spaces.

PMID- 24587740
TI  - Thermodynamic, kinetic, and equilibrium parameters for the removal of lead and
      cadmium from aqueous solutions with calcium alginate beads.
AB  - The sorption of cadmium (Cd) and lead (Pb) by calcium alginate beads (CAB) from
      aqueous solutions in batch systems was investigated. The kinetic and
      thermodynamic parameters, as well as the sorption capacities of CAB in each
      system at different temperatures, were evaluated. The rate of sorption for both
      metals was rapid in the first 10 minutes and reached a maximum in 50 minutes.
      Sorption kinetic data were fitted to Lagergren, pseudo-second-order and Elovich
      models and it was found that the second-order kinetic model describes these data
      for the two metals; comparing kinetic parameters for Cd and Pb sorption a higher
      kinetic rate (K2) for Pb was observed, indicating that the interaction between
      lead cations and alginate beads was faster than for cadmium. Similarly, isotherm
      data were fitted to different models reported in literature and it was found that
      the Langmuir-Freundlich (L-F) and Dubinin-Radushkevich (D-R) models describe the
      isotherms in all cases. CAB sorption capacity for cadmium was 27.4 mg/g and 150.4
      mg/g for lead, at 25  degrees C. Sorption capacities of Cd and Pb increase as
      temperature rises. According to the thermodynamic parameters, the cadmium and
      lead adsorption process was spontaneous and endothermic. It was also found that
      pH has an important effect on the adsorption of these metals by CAB, as more were
      removed at pH values between 6 and 7.

PMID- 24587741
TI  - Perinatal stress, fatigue, depressive symptoms, and immune modulation in late
      pregnancy and one month postpartum.
AB  - Stress and fatigue are common complaints of pregnant and postpartum women as is
      depression. These symptoms may be related to immunomodulation. However, few
      studies have examined these relationships. The aim of this study was to examine
      the relationships among stress, fatigue, depression, and cytokines as markers of
      immune modulation in prenatal and postpartum women. Women completed
      questionnaires and gave blood samples during late pregnancy and again at 4-6
      weeks postpartum. Blood was analyzed for cytokines as measures of immune
      modulation. Stress, fatigue, and depression were experienced at moderately high
      levels, with higher levels of fatigue and depression in the postpartum but higher
      stress in the prenatal period. Levels of several cytokines were increased in the
      postpartum over the prenatal period. Stress and depression were related in the
      prenatal period and stress, depression, and fatigue were related in the
      postpartum. While various cytokines were related to each other in both periods,
      only stress was related to MIP-1beta, a cytokine that may be important for
      childbirth processes. More studies, especially longitudinal and interventional
      studies, are needed to increase our knowledge about etiology, patterns, symptoms,
      factors, and management of maternal distress. The search for reliable biomarkers
      for at-risk mothers remains a priority.

PMID- 24587742
TI  - The relationship between climbing ability and physiological responses to rock
      climbing.
AB  - AIM: The aim of this study was to examine the relationship between submaximal and
      maximal physiological responses to rock climbing for climbers of differing
      abilities. METHODS: Twenty-six male climbers performed a submaximal climbing test
      on a known circuit at 90 degrees  (vertical) and 105 degrees  (15 degrees 
      overhanging) inclination and speed 25 movements . min(-1). A maximal test was
      undertaken on a similar circuit at the same speed with inclination increasing by
      10 degrees  for each successive 3 min stage. RESULTS: Mean oxygen consumption and
      heart rate (HR) increased with wall inclination and climbers reached a mean (+/-
      SD) peak VO2 of 40.3 +/- 3.5 mL . kg(-1) . min(-1) during the maximal test. Self
      reported climbing ability was negatively correlated with VO2 and HR during the
      submaximal test at 90 degrees  (VO2, r = -0.82; HR, and r = -0.66) and at 105
      degrees  (VO2, r = -0.84; HR, and r = -0.78) suggesting an increased exercise
      economy for climbers with a higher ability level. CONCLUSION: Findings from this
      study indicate that there is a relationship between wall inclination and the
      physiological demand of a climb. However, the increased technical ability and
      fitness of higher level climbers appears to an extent to offset the increased
      demand through improved exercise economy which in turn leads to an increased time
      to exhaustion and an improvement in performance.

PMID- 24587743
TI  - The enzymatic decolorization of textile dyes by the immobilized polyphenol
      oxidase from quince leaves.
AB  - Water pollution due to release of industrial wastewater has already become a
      serious problem in almost every industry using dyes to color its products. In
      this work, polyphenol oxidase enzyme from quince (Cydonia Oblonga) leaves
      immobilized on calcium alginate beads was used for the successful and effective
      decolorization of textile industrial effluent. Polyphenol oxidase (PPO) enzyme
      was extracted from quince (Cydonia Oblonga) leaves and immobilized on calcium
      alginate beads. The kinetic properties of free and immobilized PPO were
      determined. Quince leaf PPO enzyme stability was increased after immobilization.
      The immobilized and free enzymes were employed for the decolorization of textile
      dyes. The dye solutions were prepared in the concentration of 100 mg/L in
      distilled water and incubated with free and immobilized quince (Cydonia Oblonga)
      leaf PPO for one hour. The percent decolorization was calculated by taking
      untreated dye solution. Immobilized PPO was significantly more effective in
      decolorizing the dyes as compared to free enzyme. Our results showed that the
      immobilized quince leaf PPO enzyme could be efficiently used for the removal of
      synthetic dyes from industrial effluents. 

PMID- 24587744
TI  - Antioxidant property of aerial parts and root of Phyllanthus fraternus Webster,
      an important medicinal plant.
AB  - In present study free radical scavenging potential of aerial parts and root of
      Phyllanthus fraternus was investigated. Extraction was done in water and ethanol.
      Total antioxidant capacity was measured by DPPH free radical scavenging method;
      ethanolic extract of aerial part was most potent in activity with 50% inhibition
      at 258 MUg/mL concentration. Lipid peroxidation (LPO) was measured in terms of
      thiobarbituric acid-reactive substances (TBARS) by using egg-yolk homogenates as
      lipid-rich media with EC50 of aerial part (ethanolic) 1522 MUg/mL which was found
      to be most active. Superoxide (SO) radical scavenging activity was measured using
      riboflavin-light-nitroblue tetrazolium assay. Ethanolic and aqueous extract of
      both aerial part and root was almost similar in superoxide radical scavenging
      activity. Reducing power was determined on the basis of Fe3+-Fe+ transformation
      in the presence of extract. Total phenolic and flavonoid contents were also
      measured by spectroscopic method. Results showed that the ethanolic fraction of
      aerial part is most active towards antioxidant potential and this activity is
      related to its polyphenolic content and reducing potential. Thus, P. fraternus
      extract can be used as potent natural antioxidant.

PMID- 24587745
TI  - Differential evolutionary constraints in the evolution of chemoreceptors: a
      murine and human case study.
AB  - Chemoreception is among the most important sensory modalities in animals.
      Organisms use the ability to perceive chemical compounds in all major ecological
      activities. Recent studies have allowed the characterization of chemoreceptor
      gene families. These genes present strikingly high variability in copy numbers
      and pseudogenization degrees among different species, but the mechanisms
      underlying their evolution are not fully understood. We have analyzed the
      functional networks of these genes, their orthologs distribution, and performed
      phylogenetic analyses in order to investigate their evolutionary dynamics. We
      have modeled the chemosensory networks and compared the evolutionary constraints
      of their genes in Mus musculus, Homo sapiens, and Rattus norvegicus. We have
      observed significant differences regarding the constraints on the orthologous
      groups and network topologies of chemoreceptors and signal transduction
      machinery. Our findings suggest that chemosensory receptor genes are less
      constrained than their signal transducing machinery, resulting in greater
      receptor diversity and conservation of information processing pathways. More
      importantly, we have observed significant differences among the receptors
      themselves, suggesting that olfactory and bitter taste receptors are more
      conserved than vomeronasal receptors. 

PMID- 24587746
TI  - A particle swarm optimization variant with an inner variable learning strategy.
AB  - Although Particle Swarm Optimization (PSO) has demonstrated competitive
      performance in solving global optimization problems, it exhibits some limitations
      when dealing with optimization problems with high dimensionality and complex
      landscape. In this paper, we integrate some problem-oriented knowledge into the
      design of a certain PSO variant. The resulting novel PSO algorithm with an inner
      variable learning strategy (PSO-IVL) is particularly efficient for optimizing
      functions with symmetric variables. Symmetric variables of the optimized function
      have to satisfy a certain quantitative relation. Based on this knowledge, the
      inner variable learning (IVL) strategy helps the particle to inspect the relation
      among its inner variables, determine the exemplar variable for all other
      variables, and then make each variable learn from the exemplar variable in terms
      of their quantitative relations. In addition, we design a new trap detection and
      jumping out strategy to help particles escape from local optima. The trap
      detection operation is employed at the level of individual particles whereas the
      trap jumping out strategy is adaptive in its nature. Experimental simulations
      completed for some representative optimization functions demonstrate the
      excellent performance of PSO-IVL. The effectiveness of the PSO-IVL stresses a
      usefulness of augmenting evolutionary algorithms by problem-oriented domain
      knowledge. 

PMID- 24587747
TI  - Strongly localized image states of spherical graphitic particles.
AB  - We investigate the localization of charged particles by the image potential of
      spherical shells, such as fullerene buckyballs. These spherical image states
      exist within surface potentials formed by the competition between the attractive
      image potential and the repulsive centripetal force arising from the angular
      motion. The image potential has a power law rather than a logarithmic behavior.
      This leads to fundamental differences in the nature of the effective potential
      for the two geometries. Our calculations have shown that the captured charge is
      more strongly localized closest to the surface for fullerenes than for
      cylindrical nanotube. 

PMID- 24587748
TI  - Frequency selective properties of coaxial transmission lines loaded with combined
      artificial inclusions.
AB  - The properties of a modified coaxial transmission line by periodic inclusions
      will be discussed. The introduction of split ring resonators, conductor stubs,
      air gaps, and combination of these gives rise to new frequency selective
      properties, such as stopband or passband behavior, observable in planar as well
      as volumetric metamaterial structures. These results envisage new potential
      applications and implementation of devices in coaxial transmission line
      technology. 

PMID- 24587749
TI  - A group based key sharing and management algorithm for vehicular ad hoc networks.
AB  - Vehicular ad hoc networks (VANETs) are one special type of ad hoc networks that
      involves vehicles on roads. Typically like ad hoc networks, broadcast approach is
      used for data dissemination. Blind broadcast to each and every node results in
      exchange of useless and irrelevant messages and hence creates an overhead.
      Unicasting is not preferred in ad-hoc networks due to the dynamic topology and
      the resource requirements as compared to broadcasting. Simple broadcasting
      techniques create several problems on privacy, disturbance, and resource
      utilization. In this paper, we propose media mixing algorithm to decide what
      information should be provided to each user and how to provide such information.
      Results obtained through simulation show that fewer number of keys are needed to
      share compared to simple broadcasting. Privacy is also enhanced through this
      approach. 

PMID- 24587750
TI  - Stability of a quartic functional equation.
AB  - We obtain the general solution of the generalized quartic functional equation f(x
      + my) + f(x - my) = 2(7m - 9)(m - 1)f(x) + 2m2(m2 - 1)f(y)-(m - 1)2 f(2x) +
      m2{f(x + y) + f(x - y)} for a fixed positive integer m. We prove the Hyers-Ulam
      stability for this quartic functional equation by the directed method and the
      fixed point method on real Banach spaces. We also investigate the Hyers-Ulam
      stability for the mentioned quartic functional equation in non-Archimedean
      spaces.

PMID- 24587751
TI  - Chemoenzymatic epoxidation of alkenes and reusability study of the phenylacetic
      acid.
AB  - Here, we focused on a simple enzymatic epoxidation of alkenes using lipase and
      phenylacetic acid. The immobilised Candida antarctica lipase B, Novozym 435 was
      used to catalyse the formation of peroxy acid instantly from hydrogen peroxide
      (H2O2) and phenylacetic acid. The peroxy phenylacetic acid generated was then
      utilised directly for in situ oxidation of alkenes. A variety of alkenes were
      oxidised with this system, resulting in 75-99% yield of the respective epoxides.
      On the other hand, the phenylacetic acid was recovered from the reaction media
      and reused for more epoxidation. Interestingly, the waste phenylacetic acid had
      the ability to be reused for epoxidation of the 1-nonene to 1-nonene oxide,
      giving an excellent yield of 90%. 

PMID- 24587752
TI  - Molecular divergence and species delimitation of the cultivated oyster mushrooms:
      integration of IGS1 and ITS.
AB  - Identification of edible mushrooms particularly Pleurotus genus has been
      restricted due to various obstacles. The present study attempted to use the
      combination of two variable regions of IGS1 and ITS for classifying the
      economically cultivated Pleurotus species. Integration of the two regions proved
      a high ability that not only could clearly distinguish the species but also
      served sufficient intraspecies variation. Phylogenetic tree (IGS1+ITS) showed
      seven distinct clades, each clade belonging to a separate species group.
      Moreover, the species differentiation was tested by AMOVA and the results were
      reconfirmed by presenting appropriate amounts of divergence (91.82% among and
      8.18% within the species). In spite of achieving a proper classification of
      species by combination of IGS1 and ITS sequences, the phylogenetic tree showed
      the misclassification of the species of P. nebrodensis and P. eryngii var.
      ferulae with other strains of P. eryngii. However, the constructed median joining
      (MJ) network could not only differentiate between these species but also offer a
      profound perception of the species' evolutionary process. Eventually, due to the
      sufficient variation among and within species, distinct sequences, simple
      amplification, and location between ideal conserved ribosomal genes, the
      integration of IGS1 and ITS sequences is recommended as a desirable DNA barcode.

PMID- 24587753
TI  - Carbonaceous aerosols in fine particulate matter of Santiago Metropolitan Area,
      Chile.
AB  - Measurements of carbonaceous aerosols in South American cities are limited, and
      most existing data are of short term and limited to only a few locations. For 6
      years (2002-2007), concentrations of fine particulate matter and organic and
      elemental carbon were measured continuously in the capital of Chile. The
      contribution of carbonaceous aerosols to the primary and secondary fractions was
      estimated at three different sampling sites and in the warm and cool seasons. The
      results demonstrate that there are significant differences in the levels in both
      the cold (March to August) and warm (September to February) seasons at all sites
      studied. The percent contribution of total carbonaceous aerosol fine particulate
      matter was greater in the cool season (53 +/- 41%) than in the warm season (44 +/
      18%). On average, the secondary organic carbon in the city corresponded to 29%
      of the total organic carbon. In cold periods, this proportion may reach an
      average of 38%. A comparison of the results with the air quality standards for
      fine particulate matter indicates that the total carbonaceous fraction alone
      exceeds the World Health Organization standard (10 ug/m(3)) and the United States
      Environmental Protection Agency standard (15 ug/m(3)) for fine particulate
      matter.

PMID- 24587754
TI  - Effect of storage on the physicochemical and flavour attributes of two cultivars
      of strawberry cultivated in Northern India.
AB  - An attempt was made to understand the changes in physicochemical quality (total
      soluble solids, titratable acidity, ascorbic acid, total sugars, total phenolics,
      anthocyanin content, and cupric reducing antioxidant capacity assay) and total
      volatile/aroma compounds of two cultivars of strawberry (Camarosa and Chandler)
      during storage at 5 degrees C for 9 days at an interval of three days.
      Observations indicated a significant quantitative difference both in the
      physicochemical and in total volatile content among the cultivars indicating the
      importance of cultivar for determining the postharvest quality and shelf life. At
      the end of 9 days of storage significant changes in the physicochemical and total
      volatile/aroma compounds were observed. Total antioxidants and total phenols were
      found to increase significantly, whereas total soluble solids and total sugars
      decreased with the advent of storage period for both cultivars. Total anthocyanin
      contents however remained almost constant throughout the storage period.
      Titratable acidity in Camarosa reduced with the increase in the storage period
      whereas it remained almost constant in Chandler. Ascorbic acid increased in
      Camarosa whereas the same decreased significantly in Chandler. Significantly
      higher contents of esters and terpenoids in Camarosa indicated a better retention
      of the typical fruits flavour of strawberry compared to that of Chandler.

PMID- 24587755
TI  - Comparison of three methods for wind turbine capacity factor estimation.
AB  - Three approaches to calculating capacity factor of fixed speed wind turbines are
      reviewed and compared using a case study. The first "quasiexact" approach
      utilizes discrete wind raw data (in the histogram form) and manufacturer-provided
      turbine power curve (also in discrete form) to numerically calculate the capacity
      factor. On the other hand, the second "analytic" approach employs a continuous
      probability distribution function, fitted to the wind data as well as continuous
      turbine power curve, resulting from double polynomial fitting of manufacturer
      provided power curve data. The latter approach, while being an approximation, can
      be solved analytically thus providing a valuable insight into aspects, affecting
      the capacity factor. Moreover, several other merits of wind turbine performance
      may be derived based on the analytical approach. The third "approximate"
      approach, valid in case of Rayleigh winds only, employs a nonlinear approximation
      of the capacity factor versus average wind speed curve, only requiring rated
      power and rotor diameter of the turbine. It is shown that the results obtained by
      employing the three approaches are very close, enforcing the validity of the
      analytically derived approximations, which may be used for wind turbine
      performance evaluation. 

PMID- 24587756
TI  - Applying of factor analyses for determination of trace elements distribution in
      water from Vardar and its tributaries, Macedonia/Greece.
AB  - A systematic study was carried out to investigate the distribution of fifty-six
      elements in the water samples from river Vardar (Republic of Macedonia and
      Greece) and its major tributaries. The samples were collected from 27 sampling
      sites. Analyses were performed by mass spectrometry with inductively coupled
      plasma (ICP-MS) and atomic emission spectrometry with inductively coupled plasma
      (ICP-AES). Cluster and R mode factor analysis (FA) was used to identify and
      characterise element associations and four associations of elements were
      determined by the method of multivariate statistics. Three factors represent the
      associations of elements that occur in the river water naturally while Factor 3
      represents an anthropogenic association of the elements (Cd, Ga, In, Pb, Re, Tl,
      Cu, and Zn) introduced in the river waters from the waste waters from the mining
      and metallurgical activities in the country. 

PMID- 24587757
TI  - Effect of temporal relationships in associative rule mining for web log data.
AB  - The advent of web-based applications and services has created such diverse and
      voluminous web log data stored in web servers, proxy servers, client machines, or
      organizational databases. This paper attempts to investigate the effect of
      temporal attribute in relational rule mining for web log data. We incorporated
      the characteristics of time in the rule mining process and analysed the effect of
      various temporal parameters. The rules generated from temporal relational rule
      mining are then compared against the rules generated from the classical rule
      mining approach such as the Apriori and FP-Growth algorithms. The results showed
      that by incorporating the temporal attribute via time, the number of rules
      generated is subsequently smaller but is comparable in terms of quality. 

PMID- 24587758
TI  - The dependence of global ocean modeling on background diapycnal mixing.
AB  - The Argo-derived background diapycnal mixing (BDM) proposed by Deng et al. (in
      publish) is introduced to and applied in Hybrid Coordinate Ocean Model (HYCOM).
      Sensitive experiments are carried out using HYCOM to detect the responses of
      ocean surface temperature and Meridional Overturning Circulation (MOC) to BDM in
      a global context. Preliminary results show that utilizing a constant BDM, with
      the same order of magnitude as the realistic one, may cause significant deviation
      in temperature and MOC. It is found that the dependence of surface temperature
      and MOC on BDM is prominent. Surface temperature is decreased with the increase
      of BDM, because diapycnal mixing can promote the deep cold water return to the
      upper ocean. Comparing to the control run, more striking MOC changes can be
      caused by the larger variation in BDM. 

PMID- 24587759
TI  - Successful external cephalic version: factors predicting vaginal birth.
AB  - PURPOSE: To determine the maternal and fetal outcomes of successful external
      cephalic version (ECV) as well as factors predicting vaginal birth. METHODS: The
      ECV data over a period of three years at Universiti Kebangsaan Malaysia Medical
      Centre (UKMMC) between 1 September 2008 and 30 September 2010 was reviewed. Sixty
      seven patients who had successful ECV were studied and reviewed for maternal,
      fetal, and labour outcomes. The control group comprised patients with cephalic
      singletons of matching parity who delivered following the index cases. RESULTS:
      The mean gestational age at ECV was 263 +/- 6.52 days (37.5 weeks +/- 6.52 days).
      Spontaneous labour and transient cardiotocographic (CTG) changes were the
      commonest early adverse effects following ECV. The reversion rate was 7.46%. The
      mean gestational age at delivery of the two groups was significantly different (P
      = 0.000) with 277.9 +/- 8.91 days and 269.9 +/- 9.68 days in the study group and
      control groups, respectively. The study group needed significantly more
      inductions of labour. They required more operative deliveries, had more blood
      loss at delivery, a higher incidence of meconium-stained liquor, and more cord
      around the neck. Previous flexed breeches had a threefold increase in caesarean
      section rate compared to previous extended breeches (44.1% versus 15.2%, P =
      0.010). On the contrary, an amniotic fluid index (AFI) of 13 or more is
      significantly associated with a higher rate of vaginal birth (86.8% versus 48.3%,
      P = 0.001). CONCLUSIONS: Patients with successful ECV were at higher risk of
      carrying the pregnancy beyond 40 weeks and needing induction of labour, with a
      higher rate of caesarean section and higher rates of obstetrics complications.
      Extended breech and AFI 13 or more were significantly more likely to deliver
      vaginally postsuccessful ECV. This additional information may be useful to
      caution a patient with breech that ECV does not bring them to behave exactly like
      a normal cephalic, so that they have more realistic expectations. However, these
      predictive factors needed further confirmation and hopefully, in the future, they
      would be able to further enhance counselling prior to ECV.

PMID- 24587760
TI  - Two-step single slope/SAR ADC with error correction for CMOS image sensor.
AB  - Conventional two-step ADC for CMOS image sensor requires full resolution noise
      performance in the first stage single slope ADC, leading to high power
      consumption and large chip area. This paper presents an 11-bit two-step single
      slope/successive approximation register (SAR) ADC scheme for CMOS image sensor
      applications. The first stage single slope ADC generates a 3-bit data and 1
      redundant bit. The redundant bit is combined with the following 8-bit SAR ADC
      output code using a proposed error correction algorithm. Instead of requiring
      full resolution noise performance, the first stage single slope circuit of the
      proposed ADC can tolerate up to 3.125% quantization noise. With the proposed
      error correction mechanism, the power consumption and chip area of the single
      slope ADC are significantly reduced. The prototype ADC is fabricated using 0.18
      MU m CMOS technology. The chip area of the proposed ADC is 7 MU m * 500 MU m. The
      measurement results show that the energy efficiency figure-of-merit (FOM) of the
      proposed ADC core is only 125 pJ/sample under 1.4 V power supply and the chip
      area efficiency is 84 k  MU m(2) . cycles/sample.

PMID- 24587761
TI  - Lipophilicity assessment of ruthenium(II)-arene complexes by the means of
      reversed-phase thin-layer chromatography and DFT calculations.
AB  - The lipophilicity of ten ruthenium(II)-arene complexes was assessed by reversed
      phase thin-layer chromatography (RP-TLC) on octadecyl silica stationary phase.
      The binary solvent systems composed of water and acetonitrile were used as mobile
      phase in order to determine chromatographic descriptors for lipophilicity
      estimation. Octanol-water partition coefficient, logK(OW), of tested complexes
      was experimentally determined using twenty-eight standard solutes which were
      analyzed under the same chromatographic conditions as target substances. In
      addition, ab initio density functional theory (DFT) computational approach was
      employed to calculate logK(OW) values from the differences in Gibbs' free
      solvation energies of the solute transfer from n-octanol to water. A good overall
      agreement between DFT calculated and experimentally determined logK(OW) values
      was established (R(2) = 0.8024-0.9658).

PMID- 24587762
TI  - Cardiometabolic risk factors in patients with erectile dysfunction.
AB  - INTRODUCTION: There is an increasing interest in the association between erectile
      dysfunction (ED) and cardiovascular risk factor. Epicardial adipose tissue (EAT)
      is associated with insulin resistance, increased cardiometabolic risk, and
      coronary artery disease. Our aim was to investigate relationships between
      epicardial fat thickness (EFT) as a cardiometabolic risk factor and erectile
      dysfunction. METHOD: We selected 30 erectile dysfunction patients without
      comorbidities and 30 healthy individuals. IIEF-5 score was applied to all
      patients, and IIEF-5 score below 22 was considered as erectile dysfunction. EFT
      was measured by echocardiography. RESULTS: Body mass index (BMI) was higher in ED
      patients than those without ED (28.19 +/- 4.45 kg/m(2) versus 23.84 +/- 2.36
      kg/m(2), P = 0.001, resp.). Waist circumstance (WC) was higher in ED patients
      than those without ED (106.60 +/- 5.90 versus 87.86 +/- 14.51, P = 0.001, resp.).
      EFT was higher in ED patients compared to non-ED patients (0.49 +/- 0.09 cm
      versus 0.45 +/- 0.03 cm, P = 0.016, resp.). There was positive correlation among
      BMI, WC, and EFT. There was negative correlation between EFT and IIEF-5 score (r
      : - 0.632, P = 0.001). CONCLUSION: EAT, BMI, and WC as cardiometabolic risk
      factors were higher in erectile dysfunction patients.

PMID- 24587763
TI  - Prediction of tetraoxygen reaction mechanism with sulfur atom on the singlet
      potential energy surface.
AB  - The mechanism of S+O4 (D(2h)) reaction has been investigated at the B3LYP/6
      311+G(3df) and CCSD levels on the singlet potential energy surface. One stable
      complex has been found for the S+O4 (D(2h)) reaction, IN1, on the singlet
      potential energy surface. For the title reaction, we obtained four kinds of
      products at the B3LYP level, which have enough thermodynamic stability. The
      results reveal that the product P3 is spontaneous and exothermic with -188.042
      and -179.147 kcal/mol in Gibbs free energy and enthalpy of reaction,
      respectively. Because P1 adduct is produced after passing two low energy level
      transition states, kinetically, it is the most favorable adduct in the 1S+1O4
      (D(2h)) atmospheric reactions.

PMID- 24587764
TI  - The comparison of pain caused by suprapubic aspiration and transurethral
      catheterization methods for sterile urine collection in neonates: a randomized
      controlled study.
AB  - This study was performed to compare the levels of pain experienced by young
      infants undergoing either suprapubic aspiration (SPA) or transurethral
      catheterization (TUC) for the collection of sterile urine samples. This
      prospective randomized clinical trial was conducted in hospitalized neonates in a
      university-affiliated hospital. Patients who required urine cultures were
      randomly assigned into one of two groups, the SPA or TUC group. The infants'
      faces were videotaped, and the changes in the facial expression and physiological
      parameters during the procedure were scored using the Premature Infant Pain
      Profile (PIPP) in a blind manner. The primary outcome was the severity of the
      pain experienced during each procedure, and the secondary outcomes were the
      success rate, the duration, and the complications of each procedure. Ninety-four
      percent of male infants in the TUC group and 77.3% in the SPA group were
      uncircumcised (P = 0.1). The mean (SD) of the PIPP pain scores did not differ
      between groups (9.95 +/- 3.7 in SPA and 9.64 +/- 3.2 in TUC, P = 0.6). The
      duration of TUC was longer. Both methods can be used to collect urine from
      neonates, but the difficulty of performing TUC on females and uncircumcised males
      should be considered. 

PMID- 24587765
TI  - Discovery of novel inhibitors for Nek6 protein through homology model assisted
      structure based virtual screening and molecular docking approaches.
AB  - Nek6 is a member of the NIMA (never in mitosis, gene A)-related serine/threonine
      kinase family that plays an important role in the initiation of mitotic cell
      cycle progression. This work is an attempt to emphasize the structural and
      functional relationship of Nek6 protein based on homology modeling and binding
      pocket analysis. The three-dimensional structure of Nek6 was constructed by
      molecular modeling studies and the best model was further assessed by PROCHECK,
      ProSA, and ERRAT plot in order to analyze the quality and consistency of
      generated model. The overall quality of computed model showed 87.4% amino acid
      residues under the favored region. A 3 ns molecular dynamics simulation confirmed
      that the structure was reliable and stable. Two lead compounds (Binding database
      ID: 15666, 18602) were retrieved through structure-based virtual screening and
      induced fit docking approaches as novel Nek6 inhibitors. Hence, we concluded that
      the potential compounds may act as new leads for Nek6 inhibitors designing.

PMID- 24587766
TI  - Verification and optimal control of context-sensitive probabilistic Boolean
      networks using model checking and polynomial optimization.
AB  - One of the significant topics in systems biology is to develop control theory of
      gene regulatory networks (GRNs). In typical control of GRNs, expression of some
      genes is inhibited (activated) by manipulating external stimuli and expression of
      other genes. It is expected to apply control theory of GRNs to gene therapy
      technologies in the future. In this paper, a control method using a Boolean
      network (BN) is studied. A BN is widely used as a model of GRNs, and gene
      expression is expressed by a binary value (ON or OFF). In particular, a context
      sensitive probabilistic Boolean network (CS-PBN), which is one of the extended
      models of BNs, is used. For CS-PBNs, the verification problem and the optimal
      control problem are considered. For the verification problem, a solution method
      using the probabilistic model checker PRISM is proposed. For the optimal control
      problem, a solution method using polynomial optimization is proposed. Finally, a
      numerical example on the WNT5A network, which is related to melanoma, is
      presented. The proposed methods provide us useful tools in control theory of
      GRNs. 

PMID- 24587767
TI  - Estrogen-responsive genes overlap with triiodothyronine-responsive genes in a
      breast carcinoma cell line.
AB  - It has been well established that estrogen plays an important role in the
      progression and treatment of breast cancer. However, the role of triiodothyronine
      (T3) remains controversial. We have previously shown its capacity to stimulate
      the development of positive estrogen receptor breast carcinoma, induce the
      expression of genes (PR, TGF-alpha) normally stimulated by estradiol (E2), and
      suppress genes (TGF-beta) normally inhibited by E2. Since T3 regulates growth
      hormones, metabolism, and differentiation, it is important to verify its action
      on other genes normally induced by E2. Therefore, we used DNA microarrays to
      compare gene expression patterns in MCF-7 breast adenocarcinoma cells treated
      with E2 and T3. Several genes were modulated by both E2 and T3 in MCF-7 cells
      (Student's t-test, P < 0.05). Specifically, we found eight genes that were
      differentially expressed after treatment with both E2 and T3, including
      amphiregulin, fibulin 1, claudin 6, pericentriolar material 1, premature ovarian
      failure 1B, factor for adipocyte differentiation-104, sterile alpha motif domain
      containing 9, and likely ortholog of rat vacuole membrane protein 1 (fold change
      > 2.0, pFDR < 0.05). We confirmed our microarray results by real-time PCR. Our
      findings reveal that certain genes in MCF-7 cells can be regulated by both E2 and
      T3.

PMID- 24587768
TI  - In vitro culture conditions and OeARF and OeH3 expressions modulate adventitious
      root formation from oleaster (Olea europaea L. subsp. europaea var. sylvestris)
      cuttings.
AB  - Olea europaea L. subsp. europaea var. sylvestris, also named oleaster, is the
      wild form of olive and it is used as rootstock and pollen donor for many
      cultivated varieties. An efficient procedure for in vitro propagation of oleaster
      was established in this study. A zeatin concentration of 2.5 mg/L was effective
      to induce an appreciable vegetative growth. Also high rooting efficiency was
      obtained by using a short IBA pulse, followed by two different IBA concentrations
      in the culture medium. With the aim to enlarge knowledge on the molecular aspects
      of adventitious rooting, we also evaluated the transcriptional modulation of an
      ARFs member and HISTONE H3 genes, involved in auxin signaling and cell
      replication, respectively, during the root induction phase of cuttings. The
      obtained results suggest that the selected genes, as markers of the induction
      phase, could be very useful for setting up efficient culture conditions along the
      rooting process, thus increasing micropropagation efficiency. 

PMID- 24587769
TI  - Reducing the Excess Burden of Cervical Cancer Among Latinas: Translating Science
      into Health Promotion Initiatives.
AB  - PURPOSE: Although deaths from cervical cancer are declining, Latinas are not
      benefiting equally in this decline. Incidence of invasive cervical cancer among
      Los Angeles', California Latinas is much higher than among non-Latina Whites
      (14.7 versus 8.02 per 100,000). This paper examines cervical cancer screening
      among Latinas. METHODS: Ninety-seven women of Mexican origin participated in 12
      focus groups exploring barriers to screening. Saturation was reached. RESULTS:
      All participants knew what a Pap test was and most knew its purpose. More
      acculturated participants understood the link between HPV and cervical cancer.
      More recent immigrants did not. There was confusion whether women who were not
      sexually active need to be screened. Most frequently mentioned barriers were lack
      of time and concern over missing work. Lower income and less acculturated women
      were less likely to be aware of free/low-cost clinics. Older and less
      acculturated participants held more fatalistic beliefs, were more embarrassed
      about getting a Pap test, were more fearful of being perceived as sexually
      promiscuous, and were more fearful of receiving disapproval from their husbands.
      CONCLUSIONS: Latinas are informed regarding cervical cancer screening; rather
      they encounter barriers such as a lack of time, money and support. Health
      promotion interventions can be enhanced via peer-to-peer education, by addressing
      barriers to cervical cancer screening with in-language, culturally tailored
      interventions, and working with clinics on systemic changes, such as extended
      clinic hours.

PMID- 24587770
TI  - Improving the Resistance Profile of Hepatitis C NS3/4A Inhibitors: Dynamic
      Substrate Envelope Guided Design.
AB  - Drug resistance is a principal concern in the treatment of quickly evolving
      diseases. The viral protease NS3/4A is a primary drug target for the hepatitis C
      virus (HCV) and is known to evolve resistance mutations in response to drug
      therapy. At the molecular level, drug resistance reflects a subtle change in the
      balance of molecular recognition by NS3/4A; the drug resistant protease variants
      are no longer effectively inhibited by the competitive active site inhibitors but
      can still process the natural substrates with enough efficiency for viral
      survival. In previous works we have developed the "substrate envelope"
      hypothesis, which posits that inhibitors should be less susceptible to drug
      resistance if they better mimic the natural substrate molecular recognition
      features. In this work, we perform molecular dynamics simulations on four native
      substrates bound to NS3/4A and discover a clearly conserved dynamic substrate
      envelope. We show that the most severe drug resistance mutations in NS3/4A occur
      at residues that are outside the substrate envelope. Comparative analysis of
      three NS3/4A inhibitors reveals structural and dynamic characteristics of
      inhibitors that could lead to resistance. We also suggest inhibitor modifications
      to improve resistance profiles based on the dynamic substrate envelope. This
      study provides a general framework for guiding the development of novel
      inhibitors that will be more robust against resistance by mimicking the static
      and dynamic binding characteristics of natural substrates.

PMID- 24587771
TI  - Sonochemical synthesis of silver nanoparticles using starch: a comparison.
AB  - A novel approach was applied to synthesize silver nanoparticles using starch
      under sonication. Colloidal silver nanoparticles solution exhibited an increase
      of absorption from 420 to 440 nm with increase starch quantity. Transmission
      electron microscopy followed by selected area electron diffraction pattern
      analysis indicated the formation of spherical, polydispersed, amorphous, silver
      nanoparticles of diameter ranging from 23 to 97 nm with mean particle size of
      45.6 nm. Selected area electron diffraction (SAED) confirmed partial crystalline
      and amorphous nature of silver nanoparticles. Silver nanoparticles synthesized in
      this manner can be used for synthesis of 2-aryl substituted benzimidazoles which
      have numerous biomedical applications. The optimized reaction conditions include
      10 ml of 1 mM AgNO3, 25 mg starch, 11 pH range, and sonication for 20 min at room
      temperature. 

PMID- 24587772
TI  - DNA Vaccines for Prostate Cancer.
AB  - Delivery of plasmid DNA encoding an antigen of interest has been demonstrated to
      be an effective means of immunization, capable of eliciting antigen-specific T
      cells. Plasmid DNA vaccines offer advantages over other anti-tumor vaccine
      approaches in terms of simplicity, manufacturing, and possibly safety. The
      primary disadvantage is their poor transfection efficiency and subsequent lower
      immunogenicity relative to other genetic vaccine approaches. However, multiple
      preclinical models demonstrate anti-tumor efficacy, and many efforts are underway
      to improve the immunogenicity and anti-tumor effect of these vaccines. Clinical
      trials using DNA vaccines as treatments for prostate cancer have begun, and to
      date have demonstrated safety and immunological effect. This review will focus on
      DNA vaccines as a specific means of antigen delivery, advantages and
      disadvantages of this type of immunization, previous experience in preclinical
      models and human trials specifically conducted for the treatment of prostate
      cancer, and future directions for the application of DNA vaccines to prostate
      cancer immunotherapy.

PMID- 24587773
TI  - Oral cavity and oropharyngeal squamous cell carcinoma in young adults: a review
      of the literature.
AB  - BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is a disease of middle
      aged to elderly adults. However, an increased incidence of HNSCC in young people
      under 45 years of age has been reported recently. In the present review, we
      focused on the epidemiology and aetiology of HNSCC in adults under 45 years of
      age. METHODS: We reviewed literature related to HNSCC in adult patients less than
      45 years of age and discussed current treatment options and prognosis. RESULTS:
      HNSCC in young adults is associated with a higher incidence rate in nonsmokers,
      lower female-to-male ratio, a higher percentage of oral cavity and oropharynx
      tumours, and fewer second primary tumours. However, aside from traditional risk
      factors of tobacco and alcohol exposure, the causes of these cancers in young
      adults remain unclear. Agents that might contribute to risk include infection
      with high-risk human papillomavirus subtypes as well as genetic factors or
      immunodeficiency status. The expected increase in incidence and mortality of the
      young with HNSCC may become a major public health concern if current trends
      persist, particularly lifestyle habits that may contribute to this disease.
      CONCLUSIONS: Given the younger age and potential long-term adverse sequelae of
      traditional HNSCC treatments, young adults should be treated on a case-by-case
      basis and post-therapy quality of life must be considered in any treatment
      decision making process.

PMID- 24587774
TI  - Pancreatic involvement in small cell lung cancer.
AB  - BACKGROUND: Few data are available concerning incidence, clinical picture, and
      prognosis for pancreatic metastases of small cell lung carcinoma. In this paper
      we review the related literature available in English language. CONCLUSIONS:
      Although pancreatic metastases are generally asymptomatic, they can rarely
      produce clinical symptoms or functional abnormalities. The widespread use of
      multi-detector computerised tomography (CT) in contemporary medical practice has
      led to an increased detection of pancreatic metastases in oncology patients.
      Tissue diagnosis is imperative because radiological techniques alone are
      incapable of differentiating them from primary pancreatic tumours. Pancreatic
      metastases occur in the relative end stage of small cell lung cancer. The main
      complications of these lesions, although rare, are acute pancreatitis and
      obstructive jaundice. Early chemotherapy can provide a survival benefit even in
      patients with mild acute pancreatitis or extrahepatic biliary obstruction.

PMID- 24587776
TI  - The role of ultrasound and ultrasound-guided fine needle aspiration biopsy of
      lymph nodes in patients with skin tumours.
AB  - BACKGROUND: The primary aim of this study was to evaluate the diagnostic accuracy
      of ultrasound (US) in the study of superficial lymph nodes during the follow-up
      of patients surgically treated for skin tumours. The secondary objective was to
      compare positive cytological results with histological reports. PATIENTS AND
      METHODS: From 2004 to 2011, 480 patients (male/female: 285/195; median age 57
      years; prevalent skin tumour: melanoma) underwent US-guided fine-needle
      aspiration biopsy (FNAB) of suspicious recurrent lymph nodes. An expert
      radiologist first performed US testing of the lymph nodes, expressing either a
      negative or positive outcome of the test. Subsequently, US-guided FNAB was
      performed. FNAB positive patients were subjected to lymphadenectomy; the patients
      who tested negative underwent the follow-up. RESULTS: The size of lymph nodes was
      <= 2 cm in 90% of cases. Out of the 336 (70%) US "positive" patients, 231 (68.8%)
      were FNAB positives. Out of the 144 (30%) US "negatives", 132 (91.7%) were FNAB
      negatives. The sensitivity and specificity of the US were 95% and 55.7%,
      respectively; the negative predictive value was 91.7% and the positive predictive
      value was 68.8%. Definitive histological results confirmed FNAB positivity in
      97.5% of lymphadenectomies. CONCLUSIONS: US is a sensitive method in the
      evaluation of superficial lymph nodes during the follow-up of patients with skin
      tumours. High positive predictive value of cytology was confirmed.

PMID- 24587775
TI  - Consequence of the introduction of routine FCH PET/CT imaging for patients with
      prostate cancer: a dual centre survey.
AB  - BACKGROUND: Fluorocholine(18F) (FCH) was introduced at the beginning of April
      2010 in France, Slovenia and three other EU member states for the localisation of
      bone metastases of prostate cancer with PET. The aim of the study was to compare
      the evolution of diagnostic imaging in patients with prostate cancer using a new
      radiopharmaceutical FCH, observed in France and in Slovenia, and to quantify the
      consequence of the results of new imaging modality on the detection rate of
      abnormal metastases and recurrences of prostate cancer. PATIENTS AND METHODS: In
      two centres (France/Slovenia), a survey of the number of nuclear medicine
      examinations in patients with prostate cancer was performed, covering 5 quarters
      of the year since the introduction of FCH. For each examination, the clinical and
      biological circumstances were recorded, as well as the detection of bone or soft
      tissue foci. RESULTS: Six hundred and eighty-eight nuclear medicine examinations
      were performed impatients with prostate cancer. Nuclear medicine examinations
      were performed for therapy monitoring and follow-up in 23% of cases. The number
      of FCH PET/CT grew rapidly between the 1(st) and 5(th) period of the observation
      (+220%), while the number of bone scintigraphies (BS) and fluoride(18F) PET/CTs
      decreased (-42% and -23% respectively). Fluorodeoxyglucose(18F) (FDG) PET/CT
      remained limited to few cases of castrate-resistant or metastatic prostate cancer
      in Paris. The proportion of negative results was significantly lower with FCH
      PET/CT (14%) than with BS (49%) or fluoride(18F) PET/CT (54%). For bone
      metastases, the detection rate was similar, but FCH PET/CT was performed on
      average at lower prostate-specific antigen (PSA) levels and was less frequently
      doubtful (4% vs. 28% for BS). FCH PET/CT also showed foci in prostatic bed (53%
      of cases) or in soft tissue (35% of cases). CONCLUSIONS: A rapid development of
      FCH PET/CT was observed in both centres and led to a higher detection rate of
      prostate cancer lesions.

PMID- 24587777
TI  - Minimally invasive CT guided treatment of intraspinal synovial cyst.
AB  - BACKGROUND: Intraspinal synovial cysts of vertebral facet joints are uncommon
      cause of radicular pain as well as neurological deficits. They can be managed
      both conservatively and surgically. CASE REPORT: A 77-year old polymorbid patient
      presented with bilateral low back pain which worsened during the course of time
      and did not respond to the conservative treatment. A diagnosis of intraspinal
      synovial cyst was made using the magnetic resonance imaging (MRI). Percutaneous
      computed tomography (CT) guided injection with installation of local anesthetic
      together with corticosteroid and rupture of the cyst was successfully used. A
      month after the procedure his pain improved, the usage of analgesics diminished
      and his over-all quality of life improved. CONCLUSIONS: Percutaneous CT guided
      lumbar synovial cyst treatment is safe and reliable alternative to the surgical
      treatment in polymorbid patients with radiculopathy who are not able to tolerate
      general anesthesia and operation.

PMID- 24587778
TI  - Increased expression of SHP-1 is associated with local recurrence after
      radiotherapy in patients with nasopharyngeal carcinoma.
AB  - BACKGROUND: Nasopharyngeal carcinoma (NPC) is a major cancer in southern China.
      Src homology phosphatase-1 (SHP-1) is a tyrosine phosphatase that regulates
      growth, differentiation, cell cycle progression, and oncogenesis. We determined
      the clinical significance of SHP-1 expression in the tumours of NPC patients from
      southern China who were treated with radiotherapy. PATIENTS AND METHODS: SHP-1
      expression was determined by real-time polymerase chain reaction (PCR) and
      western blotting of NPC tissue samples of 50 patients and nasopharyngeal tissues
      of 50 non-NPC patients who had chronic nasopharyngeal inflammation. SHP-1
      expression was measured in NPC tissue samples of 206 patients by
      immunohistochemistry and survival analysis was performed. RESULTS: The tumours of
      NPC patients had significantly increased expression of SHP-1 at mRNA and protein
      levels relative to patients with chronic nasopharyngeal inflammation. Survival
      analysis of NPC patients indicated that SHP-1 expression was significantly
      associated with poor local recurrence-free survival (p = 0.008), but not with
      nodal recurrence-free survival, distant metastasis-free survival, or overall
      survival. CONCLUSIONS: SHP-1 appears to be associated with radiation resistance
      of NPC cells and can be considered as a candidate marker for prognosis and/or
      therapeutic target in patients with this type of cancer.

PMID- 24587779
TI  - Evaluation of undiagnosed solitary lung nodules according to the probability of
      malignancy in the American College of Chest Physicians (ACCP) evidence-based
      clinical practice guidelines.
AB  - BACKGROUND: This study retrospectively investigated the clinical significance of
      undiagnosed solitary lung nodules removed by surgical resection. PATIENTS AND
      METHODS: We retrospectively collected data on the age, smoking, cancer history,
      nodule size, location and spiculation of 241 patients who had nodules measuring 7
      mm to 30 mm and a final diagnosis established by histopathology. We compared the
      final diagnosis of each patient with the probability of malignancy (POM) which
      was proposed by the American College of Chest Physicians (ACCP) guidelines.
      RESULTS: Of the 241 patients, 203 patients were diagnosed to have a malignant
      lung tumor, while 38 patients were diagnosed with benign disease. There were
      significant differences in the patients with malignant and benign disease in
      terms of their age, smoking history, nodule size and spiculation. The mean value
      and the standard deviation of the POM in patients with malignant tumors were 51.7
      + 26.1%, and that of patients with benign lesions was 34.6 + 26.7%. The area
      under the receiver operating characteristic (ROC) curve (AUC) was 0.67. The best
      cut-off value provided from the ROC curve was 22.6. When the cut-off value was
      set at 22.6, the sensitivity was 83%, specificity 52%, positive predictive value
      90%, negative predictive value 36% and accuracy 77%, respectively. CONCLUSIONS:
      The clinical prediction model proposed in the ACCP guidelines showed
      unsatisfactory results in terms of the differential diagnosis between malignant
      disease and benign disease of solitary lung nodules in our study, because the
      specificity, negative predictive value and AUC were relatively low.

PMID- 24587780
TI  - Results of photon radiotherapy for unresectable salivary gland tumors: is neutron
      radiotherapy's local control superior?
AB  - BACKGROUND: The results of RTOG-MRC randomized trial of photon (n=15) versus
      neutron (n=17) therapy in the 1980's reported an improved local control (LC) with
      neutron radiotherapy for unresectable salivary gland tumors. Due to increased
      severe toxicity with neutron radiotherapy and the paucity of neutron-therapy
      centers, we analyzed our institution's results of photon radiotherapy for
      unresectable salivary gland tumors. PATIENTS AND METHODS: From 1990 to 2009, 27
      patients with unresectable salivary gland cancer underwent definitive photon
      radiotherapy at our institution. Nodal involvement on presentation was found in 9
      patients. Median dose of radiotherapy was 70 Gy. Chemotherapy was given to 18
      patients, most being platinum-based regimens. Local control (LC), locoregional
      control (LRC), distant metastasis-free survival (DMFS), overall survival (OS),
      and toxicity outcomes were assessed. RESULTS: With a median follow-up of 52.4
      months, the 2/5-year actuarial LC was 69% (95%CI +/- 21.0%)/55% (+/- 24.2%), LRC
      was 65% (+/- 21.4%)/47% (+/- 21.6%), and DMFS was 71% (+/- 21.8%)/51% (+/-
      22.8%), respectively using competing risk analysis. The median OS was 25.7
      months, and the 2/5-year OS rates were 50% (+/- 19.0%)/29% (+/- 16.6%),
      respectively. Higher histologic grade was significant for an increased rate of DM
      (intermediate grade vs. low grade, p=0.04, HR 7.93; high grade vs. low grade,
      p=0.01, HR 13.50). Thirteen (48%) patient's experienced acute grade 3 toxicity.
      Late grade 3 toxicity occurred in three (11%) patients. CONCLUSIONS: Our data
      compares favorably to neutron radiotherapy with fewer late complications. Photon
      radiotherapy is an acceptable alternative to neutron radiotherapy in patients who
      present with unresectable salivary gland tumors.

PMID- 24587781
TI  - Balloon aortic valvuloplasty (BAV) as a bridge to aortic valve replacement in
      cancer patients who require urgent non-cardiac surgery.
AB  - BACKGROUND: Balloon aortic valvuloplasty (BAV) is a percutaneous treatment option
      for severe, symptomatic aortic stenosis. Due to early restenosis and failure to
      improve long term survival, BAV is considered a palliative measure in patients
      who are not suitable for open heart surgery due to increased perioperative risk.
      BAV can be used also as a bridge to surgical or transcatheter aortic valve
      implantation (TAVI) in haemodinamically unstable patients or in patients who
      require urgent major non-cardiac surgery. PATIENTS AND METHODS: We reported on 6
      oncologic patients with severe aortic stenosis that required a major abdominal
      and gynaecological surgery. In 5 cases we performed BAV procedure alone; in one
      patient with concomitant coronary artery disease we combined BAV and percutaneous
      coronary intervention (PCI). RESULTS: With angioplasty and BAV we achieved a good
      coronary artery flow and an increase in aortic valve area without any
      periprocedural complications. After the successful procedure, we observed a
      hemodynamic and symptomatic improvement. As a consequence the operative risk for
      non-cardiac surgery decreased and the surgical treatment of cancer was done
      without complications in all the 6 cases. CONCLUSIONS: BAV can be utilized as a
      part of a complex therapy in severe aortic stenosis aimed to improve the quality
      of life, decrease the surgical risk for major non-cardiac surgery or as a bridge
      to surgical or transcatheter aortic valve implantation.

PMID- 24587782
TI  - Semirigid thoracoscopy: an effective method for diagnosing pleural malignancies.
AB  - BACKGROUND: Thoracoscopy with a semirigid instrument is a recent technique for
      diagnosing pleural diseases. The purpose of this study was to report diagnostic
      yield and complications of the method. PATIENTS AND METHODS: Patients with
      pleural effusion of unknown origin and/or pleural irregularities suspicious for
      pleural malignancy were included after less invasive means of diagnosis had
      failed. All procedures were performed under local anaesthesia with intravenous
      sedation/analgesia with a single point of entry with a semirigid thoracoscope
      (Olympus LTF-160). Data were collected prospectively between 2008 and 2012.
      RESULTS: One hundred fifteen thoracoscopies were performed on 111 patients. The
      median age was 65 years (range 28-86 years), 14.4% were female and 85.6% male.
      Seventy-three (65.8%) patients had malignant pleural disease (malignant
      mesothelioma, metastatic cancer) and 38 (34.2%) had benign disease. The
      sensitivity, negative predictive value, and accuracy of the procedure for
      malignancy were 96.0%, 93.0%, and 97.4% respectively. Pleurodesis was carried out
      in 34 patients; in 32 (94.1%) it was assessed as successful after 1 month. There
      were 24 adverse events: three empyemas/pleural infections, three bronchopleural
      fistulae after chest tube placement and lung re-expansion, five patients had
      excessive pain after pleurodesis, six patients had sedation-associated
      hypotension, and seven patients had self-limited fever after plerodesis. One
      patient died 11 days after a procedure for advanced carcinoma. CONCLUSIONS:
      Semirigid thoracoscopy is an accurate and safe method for evaluation of pleural
      diseases and useful for therapeutic talc pleurodesis.

PMID- 24587783
TI  - Glioblastoma patients in Slovenia from 1997 to 2008.
AB  - BACKGROUND: Glioblastoma is the most common primary brain tumour. It has a poor
      prognosis despite some advances in treatment that have been achieved over the
      last ten years. In Slovenia, 50 to 60 glioblastoma patients are diagnosed each
      year. In order to establish whether the current treatment options have any
      influence on the survival of the Slovenian glioblastoma patients, their data in
      the period from the beginning of the year 1997 to the end of the year 2008 have
      been analysed. PATIENTS AND METHODS: All patients treated at the Institute of
      Oncology Ljubljana from 1997 to 2008 were included in the retrospective study.
      Demographics, treatment details, and survival time after the diagnosis were
      collected and statistically analysed for the group as a whole and for subgroups.
      RESULTS: From 1997 to 2008, 527 adult patients were diagnosed with glioblastoma
      and referred to the Institute of Oncology for further treatment. Their median age
      was 59 years (from 20 to 85) and all but one had the diagnosis confirmed by a
      pathologist. Gross total resection was reported by surgeons in 261 (49.5%)
      patients; good functional status (WHO 0 or 1) after surgery was observed in 336
      (63.7%) patients, radiotherapy was performed in 422 (80.1%) patients, in 317
      (75.1%) of them with radical intent, and 198 (62.5 %) of those received some form
      of systemic treatment (usually temozolomide). The median survival of all patients
      amounted to 9.7 months. There was no difference in median survival of all
      patients or of all treated patients before or after the chemo-radiotherapy era.
      However, the overall survival of patients treated with radical intent was
      significantly better (11.4 months; p < 0.05). A better survival was also noticed
      in radically treated patients who received additional temozolomide therapy (11.4
      vs. 13.1 months; p = 0.014). The longer survival was associated with a younger
      age and a good performance status as well as with a more extensive tumour
      resection. In patients treated with radical intent, having a good performance
      status, and receiving radiotherapy and additional temozolomide therapy, the
      survival was significantly longer, based on multivariate analysis. CONCLUSIONS:
      We observed a gradual increase in the survival of glioblastoma patients who were
      treated with radical intent over the last ten years. Good functional surgery,
      advances in radiotherapy and addition of temozolomide all contributed to this
      increase. Though the increased survival seems to be more pronounced in certain
      subgroups, we have still not been able to exactly define them. Further research,
      especially in tumour biology and genetics is needed.

PMID- 24587784
TI  - Individual radiosensitivity in a breast cancer collective is changed with the
      patients' age.
AB  - BACKGROUND: Individual radiosensitivity has a crucial impact on radiotherapy
      related side effects. Our aim was to study a breast cancer collective for its
      variation of individual radiosensitivity depending on the patients' age.
      MATERIALS AND METHODS: Peripheral blood samples were obtained from 129
      individuals. Individual radiosensitivity in 67 breast cancer patients and 62
      healthy individuals was estimated by 3-color fluorescence in situ hybridization.
      RESULTS: Breast cancer patients were distinctly more radiosensitive compared to
      healthy controls. A subgroup of 9 rather radiosensitive and 9 rather radio
      resistant patients was identified. A subgroup of patients aged between 40 and 50
      was distinctly more radiosensitive than younger or older patients. CONCLUSIONS:
      In the breast cancer collective a distinct resistant and sensitive subgroup is
      identified, which could be subject for treatment adjustment. Preliminary results
      indicate that especially in the range of age 40 to 50 patients with an increased
      radiosensitivity are more frequent and may have an increased risk to suffer from
      therapy related side effects.

PMID- 24587785
TI  - Evaluation of a software system for estimating planned dose error in patients,
      based on planar IMRT QA measurements.
AB  - BACKGROUND: Intensity modulated radiation therapy (IMRT) dosimetry verification
      is routinely conducted via integrated or individual field dosimetry using film or
      a matrix of detectors. Techniques and software systems are commercially available
      which use individual field dosimetry measurements as input into algorithms that
      estimate 3D patient dose distributions on CT scan derived target volumes and
      organs at risk (OARs), thus allowing direct dose-volume histogram (DVH) analysis
      vs. treatment planning system (TPS) DVH. The purpose of this work is to present a
      systematic benchmarking technique to evaluate the accuracy and consistency of
      such a software system. METHODS: A MapCheck2 diode array and 3DVHTM software from
      Sun Nuclear were used for this study. Delivered planar dose was measured with the
      diode array as an input to 3DVHTM software that was used to estimate the 3D dose
      matrix. Accuracy of the output of 3DVHTM is tested by comparing measured planar
      doses over a range of depths to the same planes reconstructed by 3DVHTM.
      Different fields from complex IMRT cases were selected and examined in this
      study. The sensitivity to depth of measurement was evaluated. RESULTS: The Gamma
      Index analysis, comparing calculated 3D dose with measured 3D dose with 2% and
      2mm distance-to-agreement (DTA) criteria returned a pass rate of > 90% for all
      patient cases calculated by the treatment planning system and it returned a pass
      rate of > 96% in 9 out of 10 cases calculated by 3DVHTM. Extracted computed dose
      planes with 3DVHTM software at different depths in the flat phantom passed all
      gamma evaluation analyses when compared to measured planes at different depths
      using MapCheck2. CONCLUSIONS: Studying complex head and neck IMRT fields, it was
      shown that the 3D dose distribution predicted by the planned dose perturbation
      (PDP) algorithm is both accurate and consistent.

PMID- 24587786
TI  - Impact of respiratory motion on breast tangential radiotherapy using the field-in
      field technique compared to irradiation using physical wedges.
AB  - BACKGROUND: This study aimed to evaluate whether the field-in-field (FIF)
      technique was more vulnerable to the impact of respiratory motion than
      irradiation using physical wedges (PWs). PATIENTS AND METHODS: Ten patients with
      early stage breast cancer were enrolled. Computed tomography (CT) was performed
      during free breathing (FB). After the FB-CT data set acquisition, 2 additional CT
      scans were obtained during a held breath after light inhalation (IN) and light
      exhalation (EX). Based on the FB-CT images, 2 different treatment plans were
      created for the entire breast for each patient and copied to the IN-CT and EX-CT
      images. The amount of change in the volume of the target receiving 107%, 95%, and
      90% of the prescription dose (V107%, V95%, and V90%, respectively), on the IN
      plan and EX-plan compared with the FB-plan were evaluated. RESULTS: The V107%,
      V95%, and V90% were significantly larger for the IN-plan than for the FB-plan in
      both the FIF technique and PW technique. While the amount of change in the V107%
      was significantly smaller in the FIF than in the PW plan, the amount of change in
      the V95% and V90% was significantly larger in the FIF plan. Thus, the increase in
      the V107% was smaller while the increases in the V95% and V90% were larger in the
      FIF than in the PW plan. CONCLUSIONS: During respiratory motion, the dose
      parameters stay within acceptable range irrespective of irradiation technique
      used although the amount of change in dose parameters was smaller with FIF
      technique.

PMID- 24587787
TI  - Global small-angle X-ray scattering data analysis for multilamellar vesicles: the
      evolution of the scattering density profile model.
AB  - The highly successful scattering density profile (SDP) model, used to jointly
      analyze small-angle X-ray and neutron scattering data from unilamellar vesicles,
      has been adapted for use with data from fully hydrated, liquid crystalline
      multilamellar vesicles (MLVs). Using a genetic algorithm, this new method is
      capable of providing high-resolution structural information, as well as
      determining bilayer elastic bending fluctuations from standalone X-ray data.
      Structural parameters such as bilayer thickness and area per lipid were
      determined for a series of saturated and unsaturated lipids, as well as binary
      mixtures with cholesterol. The results are in good agreement with previously
      reported SDP data, which used both neutron and X-ray data. The inclusion of
      deuterated and non-deuterated MLV neutron data in the analysis improved the lipid
      backbone information but did not improve, within experimental error, the
      structural data regarding bilayer thickness and area per lipid.

PMID- 24587788
TI  - Refinement of macromolecular structures against neutron data with SHELXL2013.
AB  - Some of the improvements in SHELX2013 make SHELXL convenient to use for
      refinement of macromolecular structures against neutron data without the support
      of X-ray data. The new NEUT instruction adjusts the behaviour of the SFAC
      instruction as well as the default bond lengths of the AFIX instructions. This
      work presents a protocol on how to use SHELXL for refinement of protein
      structures against neutron data. It includes restraints extending the Engh &
      Huber [Acta Cryst. (1991), A47, 392-400] restraints to H atoms and discusses
      several of the features of SHELXL that make the program particularly useful for
      the investigation of H atoms with neutron diffraction. SHELXL2013 is already
      adequate for the refinement of small molecules against neutron data, but there is
      still room for improvement, like the introduction of chain IDs for the refinement
      of macromolecular structures.

PMID- 24587789
TI  - The geometry of Niggli reduction: BGAOL -embedding Niggli reduction and analysis
      of boundaries.
AB  - Niggli reduction can be viewed as a series of operations in a six-dimensional
      space derived from the metric tensor. An implicit embedding of the space of
      Niggli-reduced cells in a higher-dimensional space to facilitate calculation of
      distances between cells is described. This distance metric is used to create a
      program, BGAOL, for Bravais lattice determination. Results from BGAOL are
      compared with results from other metric based Bravais lattice determination
      algorithms. This embedding depends on understanding the boundary polytopes of the
      Niggli-reduced cone N in the six-dimensional space G6. This article describes an
      investigation of the boundary polytopes of the Niggli-reduced cone N in the six
      dimensional space G6 by algebraic analysis and organized random probing of
      regions near one-, two-, three-, four-, five-, six-, seven- and eightfold
      boundary polytope intersections. The discussion of valid boundary polytopes is
      limited to those avoiding the mathematically interesting but crystallographically
      impossible cases of zero-length cell edges. Combinations of boundary polytopes
      without a valid intersection in the closure of the Niggli cone or with an
      intersection that would force a cell edge to zero or without neighboring probe
      points are eliminated. In all, 216 boundary polytopes are found. There are 15
      five-dimensional boundary polytopes of the full G6 Niggli cone N .

PMID- 24587790
TI  - The geometry of Niggli reduction: SAUC - search of alternative unit cells.
AB  - A database of lattices using the G6 representation of the Niggli-reduced cell as
      the search key provides a more robust and complete search than older techniques.
      Searching is implemented by finding the distance from the probe cell to other
      cells using a topological embedding of the Niggli reduction in G6, so that all
      cells representing similar lattices will be found. The embedding provides the
      first fully linear measure of distances between unit cells. Comparison of results
      with those from older cell-based search algorithms suggests significant value in
      the new approach.

PMID- 24587791
TI  - The impact of the declining extended family support system on the education of
      orphans in Lesotho.
AB  - This paper examines the impact of the weakening of the extended family on the
      education of double orphans in Lesotho through in-depth interviews with
      participants from 3 of the 10 districts in Lesotho. The findings reveal that in
      Lesotho the extended family has not yet disintegrated as the literature suggests.
      However, it shows signs of rupturing, as many orphans reported that they are
      being taken into extended family households, the incentive for these households
      being, presumably, the financial and other material assistance that they receive
      from the government and non-governmental organisations (NGOs) which supplements
      household income and material wellbeing. The findings show that financial and
      other assistance given by the government and NGOs have resulted in conflict
      between the orphans and caregivers. This has also prompted many extended families
      to shift responsibilities to the government and NGOs. Most of the extended
      households provided the orphans with poor living conditions, such as unhygienic
      houses, poor nutrition, and little or no provision of school materials, which has
      had a negative impact on the education of the orphans. The combined effects of
      economic crisis and HIV and AIDS have resulted in extended families not being
      able to care for the needs of the orphans adequately, whilst continuing to accept
      them into their households. It is recommended that although extended families are
      still accepting orphans, the government should strengthen and recognise the
      important role played by families and the communities in caring for these
      vulnerable children. The government should also introduce social grants for
      orphans and other vulnerable children and review the current meagre public
      assistance (R100) it provides for orphans and vulnerable children in Lesotho.
      Other stakeholders should concentrate on strengthening the capacity of families
      and communities through programmes and projects which could be more sustainable
      than the current handouts given by many NGOs.

PMID- 24587792
TI  - Multigene phylogeny, taxonomy and reclassification of Hyaloperonospora on
      Cardamine.
AB  - Based on sequence data from cox1, cox2, ITS and LSU rDNA, it is shown that at
      least six species of Hyaloperonospora occur on the genus Cardamine, most of which
      were commonly classified under Peronospora dentariae. Based on sequences from
      their type hosts, Peronospora dentariae, Peronospora cardamines-laciniatae,
      Peronospora dentariae-macrophyllae, Peronospora malyi and Peronospora nasturtii
      aquatici are combined into Hyaloperonospora, and their circumscription is
      clarified. Hyaloperonospora cardamines-enneaphyllos is described as a new species
      from Cardamine enneaphyllos. The host range of Hyaloperonospora nasturtii
      aquatici, described from Nasturtium officinale, is shown to extend to various
      Cardamine species. Host range of species is shown to be highly diagnostic, with
      no overlap in their host range, but species commonly cannot be distinguished by
      morphology alone. Both cox1 and cox2 are confirmed to be good markers for
      phylogenetic species delimitation of closely related Hyaloperonospora species on
      Cardamine.

PMID- 24587793
TI  - The Proatherogenic Effect of Chronic Nitric Oxide Synthesis Inhibition in ApoE
      Null Mice Is Dependent on the Presence of PPAR alpha.
AB  - Inhibition of endothelial nitric oxide synthase (eNOS) accelerates
      atherosclerosis in ApoE-null mice by impairing the balance between angiotensin II
      (AII) and NO. Our previous data suggested a role for PPAR alpha in the
      deleterious effect of the renin-angiotensin system (RAS). We tested the
      hypothesis that ApoE-null mice lacking PPAR alpha (DKO mice) would be resistant
      to the proatherogenic effect of NOS inhibition. DKO mice fed a Western diet were
      immune to the 23% worsening in aortic sinus plaque area seen in the ApoE-null
      animals under 12 weeks of NOS inhibition with a subpressor dose of L-NAME, P =
      0.002. This was accompanied by a doubling of reactive oxygen species (ROS-)
      generating aortic NADPH oxidase activity (a target of AII, which paralleled Nox1
      expression) and by a 10-fold excess of the proatherogenic iNOS, P < 0.01. L-NAME
      also caused a doubling of aortic renin and angiotensinogen mRNA level in the ApoE
      null mice but not in the DKO, and it upregulated eNOS in the DKO mice only. These
      data suggest that, in the ApoE-null mouse, PPAR alpha contributes to the
      proatherogenic effect of unopposed RAS/AII action induced by L-NAME, an effect
      which is associated with Nox1 and iNOS induction, and is independent of blood
      pressure and serum lipids. 

PMID- 24587794
TI  - The Rate of Decline of Glomerular Filtration Rate May Not Be Associated with
      Polymorphism of the PPARgamma2 Gene in Patients with Type 1 Diabetes and
      Nephropathy.
AB  - The aim of the study was to investigate whether a Pro12Ala polymorphism in the
      peroxisome proliferator-activated receptor gamma 2 (PPAR gamma 2) gene is
      associated with the progress of diabetic nephropathy in patients with type 1
      diabetes. 197 Caucasian patients with type 1 diabetes and ethnically matched 151
      normal healthy controls were genotyped for this polymorphism. Results showed that
      there were no significant differences in the frequencies of the genotypes and
      alleles of the polymorphism between groups. Multiple regression analysis in 77
      patients demonstrated that the rate of decline in renal function in terms of
      glomerular filtration rate was significantly correlated to the baseline level of
      cholesterol (P = 0.0014), mean diastolic blood pressure during follow-up period
      (P = 0.019), and baseline level of HbA1c (P = 0.022) adjusting for the effect of
      diabetes duration and gender, but no significant association was found between
      the polymorphism and the progression of diabetic nephropathy in our studied
      population. In summary, our results show that the PPAR gamma 2 polymorphism is
      unlikely to be associated with the development and progression of the diabetic
      nephropathy in patients with type 1 diabetes. Further studies in different
      populations may be warranted to confirm our findings as the sample size in our
      study was relatively small. 

PMID- 24587795
TI  - Impact of rechallenge with imatinib in patients with advanced gastrointestinal
      stromal tumor after failure of imatinib and sunitinib.
AB  - Purpose. This retrospective, nonrandomized study investigated the effect of
      imatinib rechallenge plus best supportive care (BSC) on overall survival after
      imatinib and sunitinib treatment for patients with locally advanced or metastatic
      gastrointestinal stromal tumor (GIST). Methods. Twenty-six patients who had
      previously been exposed to both imatinib and sunitinib were enrolled in this
      study. The treatment regimen was BSC with or without imatinib, based on the
      patient's choice after discussion with his or her physician. The primary endpoint
      was overall survival, and secondary endpoints were time to treatment failure,
      clinical response rate assessed by Choi criteria, and safety. Results. Fourteen
      patients were treated with imatinib plus BSC and 12 received BSC alone. Median
      overall survival was greatly improved for the imatinib group, although
      differences were not significant (22 months for imatinib plus BSC versus 4 months
      for BSC; P = 0.058). Three patients (21%) had a clinical response in the imatinib
      group, and one had a clinical response in the BSC alone group. Imatinib was well
      tolerated. Conclusions. Rechallenge with imatinib may be associated with
      improvement in overall survival without deteriorating performance status in
      patients who failed imatinib and sunitinib. A prospective study should be
      considered to confirm the efficacy of rechallenge with imatinib. 

PMID- 24587796
TI  - Nested variant of urothelial carcinoma.
AB  - Background. Nested variant of urothelial carcinoma was added to the WHO's
      classification in 2004. Aims. To review the literature on nested variant of
      urothelial carcinoma. Results. About 200 cases of the tumour have been reported
      so far and it has the ensuing morphological features: large numbers of small
      confluent irregular nests of bland-appearing, closely packed, haphazardly
      arranged, and poorly defined urothelial cells infiltrating the lamina propria and
      the muscularis propria. The tumour has a bland histomorphologic appearance, has
      an aggressive biological behaviour, and has at times been misdiagnosed as a
      benign lesion which had led to a significant delay in the establishment of the
      correct diagnosis and contributing to the advanced stage of the disease.
      Immunohistochemically, the tumour shares some characteristic features with high
      risk conventional urothelial carcinomas such as high proliferation index and loss
      of p27 expression. However, p53, bcl-2, or EGF-r immunoreactivity is not
      frequently seen. The tumour must be differentiated from a number of proliferative
      lesions of the urothelium. Conclusions. Correct and early diagnosis of this
      tumour is essential to provide early curative treatment to avoid diagnosis at an
      advanced stage. A multicentre trial is required to identify treatment options
      that would improve the outcome of this tumour. 

PMID- 24587797
TI  - Is metabolic syndrome truly a risk factor for male lower urinary tract symptoms
      or just an epiphenomenon?
AB  - To define whether the association of male lower urinary tract symptoms (LUTS) and
      metabolic syndrome (MS) is real or simply an epiphenomenon, 490 male adults (mean
      age 58 +/- 9 years) underwent International Prostate Symptom Score (IPSS),
      physical and prostate digital examinations, blood analysis, and urinary tract
      transabdominal ultrasound with prostate volume measurement. Mild, moderate, and
      severe LUTS were found in 350 (71.4%), 116 (23.7%), and 24 (4.9%) patients,
      respectively. MS was present in 198 (40.4%) patients, representing 37.4% (131 of
      350) of those with mild LUTS, 46.5% (54 of 116) of those with moderate, and 54.1%
      (13 of 24) of those with severe. The odds ratio of MS having moderate or severe
      LUTS was 2.1. MS was more common in older age, higher body mass index, and larger
      prostate size. Moderate and severe LUTS were more frequent in older age, lower
      levels of high density cholesterol, and higher blood pressure. Older age and body
      mass index had significant relative risk for lower urinary tract symptoms and
      only age remained independent factor for LUTS on multivariate analysis. Our
      results suggest that the association of male LUTS, prostate volume, and MS might
      be coincidental and related to older age. 

PMID- 24587798
TI  - Surgical Approaches to Supradiaphragmatic Segment of IVC and Right Atrium through
      Abdominal Cavity during Intravenous Tumor Thrombus Removal.
AB  - Objective. The purpose of this study was to investigate safety and feasibility of
      some surgical approaches to the supradiaphragmatic inferior vena cava (IVC) and
      the right atrium through the diaphragm from the abdominal cavity. Materials and
      Methods. The material of the anatomical study included 35 fresh cadavers. Several
      options of surgical access to the supradiaphragmatic IVC were successively
      performed. Feasibility and risk level of each of the approaches were evaluated
      with the use of a special scale. Results. The isolation of the supradiaphragmatic
      IVC and cavoatrial junction was most easily performed via T-shaped or circular
      diaphragmotomy (grade "easy" was registered in 74.3% and 80% of patients, resp.,
      compared to 31.4% for transverse diaphragmotomy and 40% for isolation of the IVC
      in the pericardial cavity). The risk analysis has demonstrated the highest safety
      level for T-shaped diaphragmotomy (grade "safe" was registered in 60% of cases).
      The intervention via transverse diaphragmotomy, circular diaphragmotomy, and IVC
      isolation in the pericardial cavity was graded as "risky" in 80%, 62.9%, and
      82.9% of cases, respectively. Conclusions. In our opinion, T-shaped
      diaphragmotomy is the most safe and easy-to-perform access for mobilization of
      the supradiaphragmatic IVC through the abdominal cavity. 

PMID- 24587799
TI  - The Relationship between ALA16VAL Single Gene Polymorphism and Renal Cell
      Carcinoma.
AB  - Objectives. The aim of this study was to investigate the association of RCC and
      Ala16Val polymorphism in Turkish patients with RCC. Materials and Methods. A
      total of 41 patients with RCC who underwent radical or partial nephrectomy in our
      clinic and 50 healthy volunteers living in the same geographic area were included
      in this study. DNA samples from serum of RCC patients and controls were genotyped
      for MnSOD polymorphism analysis. Genotype ratios and allele frequencies were
      compared between two groups and odd ratios with 95% confidence intervals were
      calculated statistically. A P value of <0.05 was considered statistically
      significant. Results. There was a significant difference in the MnSOD genotype
      distributions between the RCC patients and the controls in terms of
      Ala/Ala+Ala/Val and Val/Val genotypes (P = 0.039). The Ala/Ala+Ala/Val genotypes
      were found significantly suspicious for RCC with an OR of 2.64 (95% CI = 1.06
      6.69, P = 0.039). In addition, Ala allele was found significantly suspicious for
      RCC with an OR of 2.26 (95% CI = 1.24-4.12, P = 0.009). Conclusion. Our study
      indicated that MnSOD Ala16Val polymorphism may be one of the many genetic factors
      for renal cancer susceptibility in Turkish patients. 

PMID- 24587800
TI  - Level of CD8 T Lymphocytes Activation in HIV-Infected Pregnant Women: In the
      Context of CD38 and HLA-DR Activation Markers.
AB  - Background. To date the effect of pregnancy on the immune activation of CD8 T
      cells that may affect HIV disease progression has not been well studied and
      remains unclear. Objective. To determine the effect of pregnancy on CD8 T
      lymphocyte activation and its relationship with CD4 count in HIV infected
      pregnant women. Study Design. Case control. Study Site. AMPATH and MTRH in
      Eldoret, Kenya. Study Subjects. Newly diagnosed asymptomatic HIV positive
      pregnant and nonpregnant women with no prior receipt of antiretroviral
      medications. Study Methods. Blood samples were collected from the study
      participants and levels of activated CD8 T lymphocytes (CD38 and HLA-DR) were
      determined using flow cytometer and correlated with CD4 counts of the study
      participants. The descriptive data focusing on frequencies, correlation, and
      cross-tabulations was statistically determined. Significance of the results was
      set at P < 0.05. Results. HIV positive pregnant women had lower activated CD8 T
      lymphocyte counts than nonpregnant HIV positive women. Activated CD8 T lymphocyte
      counts were also noted to decrease in the second and third trimesters of
      pregnancy. Conclusion. Pregnancy has a significant suppression on CD8+ T
      lymphocyte immune activation during HIV infections. Follow-up studies with more
      control arms could confirm the present study results. 

PMID- 24587801
TI  - Diabetes mellitus.

PMID- 24587802
TI  - Incidence of mast cells in oral squamous cell carcinoma: a short study.
AB  - Mast cells are regarded as complex and multifunctional cells, playing a
      significant role in immunopathology and a substantial role in tumor angiogenesis.
      Angiogenesis is a complex process that is tightly regulated by various growth
      factors in which mast cells act directly by releasing angiogenic factors and
      henceforth promoting tumor growth and metastasis. The aim of this study is to
      evaluate the number of mast cells in tissue sections of oral squamous cell
      carcinoma (OSCC) in comparison with normal mucosa. A total of 40 cases (20 OSCC
      and 20 normal mucosa) were stained with 1% toluidine blue and the quantitative
      analysis was done by using light microscope under 400x magnification. A
      significant increase in the mast cell count was observed in the sections of OSCC
      when compared to normal mucosa suggesting their contributing role in tumor growth
      and progression. 

PMID- 24587803
TI  - A model for community-based pediatric oral heath: implementation of an infant
      oral care program.
AB  - The Affordable Care Act (ACA) mandates risk assessments, preventive care, and
      evaluations based on outcomes. ACA compliance will require easily accessible,
      cost-effective care models that are flexible and simple to establish. UCLA has
      developed an Infant Oral Care Program (IOCP) in partnership with community-based
      organizations that is an intervention model providing culturally competent
      perinatal and infant oral care for underserved, low-income, and/or minority
      children aged 0-5 and their caregivers. In collaboration with the Venice Family
      Clinic's Simms/Mann Health and Wellness Center, UCLA Pediatrics, Women, Infants,
      and Children (WIC), and Early Head Start and Head Start programs, the IOCP
      increases family-centered care access and promotes early utilization of dental
      services in nontraditional, primary care settings. Emphasizing disease
      prevention, management, and care that is sensitive to cultural, language, and
      oral health literacy challenges, IOCP patients achieve better oral health
      maintenance "in health" not in "disease modality". IOCP uses interprofessional
      education to promote pediatric oral health across multiple disciplines and
      highlights the necessity for the "age-one visit". This innovative clinical model
      facilitates early intervention and disease management. It sets a new standard of
      minimally invasive dental care that is widely available and prevention focused,
      with high retention rates due to strong collaborations with the community-based
      organizations serving these vulnerable, high-risk children. 

PMID- 24587805
TI  - Necroptosis: molecular signalling and translational implications.
AB  - Necroptosis is a form of programmed necrosis whose molecular players are
      partially shared with apoptotic cell death. Here we summarize what is known about
      molecular signalling of necroptosis, particularly focusing on fine tuning of FLIP
      and IAP proteins in the apoptosis/necroptosis balance. We also emphasize
      necroptosis involvement in physiological and pathological conditions,
      particularly in the regulation of immune homeostasis. 

PMID- 24587806
TI  - Bipartite Medial Cuneiform: Case Report and Retrospective Review of 1000 Magnetic
      Resonance (MR) Imaging Studies.
AB  - Objective. To present a unique case report of a Lisfranc fracture in a patient
      with a bipartite medial cuneiform and to evaluate the prevalence of the bipartite
      medial cuneiform in a retrospective review of 1000 magnetic resonance (MR)
      imaging studies of the foot. Materials and Methods. Case report followed by a
      retrospective review of 1000 MR imaging studies of the foot for the presence or
      absence of a bipartite medial cuneiform. Results. The incidence of the bipartite
      medial cuneiform is 0.1%. Conclusion. A bipartite medial cuneiform is a rare
      finding but one with both clinical and surgical implications. 

PMID- 24587804
TI  - Mitochondrial stress signaling promotes cellular adaptations.
AB  - Mitochondrial dysfunction has been implicated in the aetiology of many complex
      diseases, as well as the ageing process. Much of the research on mitochondrial
      dysfunction has focused on how mitochondrial damage may potentiate pathological
      phenotypes. The purpose of this review is to draw attention to the less well
      studied mechanisms by which the cell adapts to mitochondrial perturbations. This
      involves communication of stress to the cell and successful induction of quality
      control responses, which include mitophagy, unfolded protein response,
      upregulation of antioxidant and DNA repair enzymes, morphological changes, and if
      all else fails apoptosis. The mitochondrion is an inherently stressful
      environment and we speculate that dysregulation of stress signaling or an
      inability to switch on these adaptations during times of mitochondrial stress may
      underpin mitochondrial dysfunction and hence amount to pathological states over
      time. 

PMID- 24587807
TI  - Evaluation of the Effects of Vaccinium arctostaphylos L. Fruit Extract on Serum
      Lipids and hs-CRP Levels and Oxidative Stress in Adult Patients with
      Hyperlipidemia: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.
AB  - Background. Dyslipidemia produces atherosclerosis, which in turn results in
      coronary artery disease (CAD). Atherosclerosis is being considered as an
      inflammatory disease. Vaccinium arctostaphylos L. is a plant with fruits rich in
      anthocyanins. The aim of this study was to evaluate the effects of fruit extract
      of this plant on serum levels of lipids, hs-CRP, and malondialdehyde (MDA) as a
      marker of oxidative stress, in hyperlipidemic adult patients. Methods. In this
      randomized, double-blind, placebo-controlled clinical trial, 50 hyperlipidemic
      adult patients were randomly and equally assigned to receive either medicinal (V.
      arctostaphylos fruit extract) or placebo capsules twice daily for 4 weeks. Each
      medicinal capsule contained 45 +/- 2 mg of anthocyanins. Fasting serum levels of
      total cholesterol, TG, LDL-C, HDL-C, hs-CRP, and MDA were obtained before and
      after the intervention and compared. Results. V. arctostaphylos fruit extract
      significantly reduced total cholesterol (P < 0.001), LDL-C (P = 0.004), TG (P <
      0.001), and MDA (P = 0.013) compared to placebo but did not have any significant
      effect on HDL-C (P = 0.631) and hs-CRP (P = 0.190). Conclusion. Fruit extract of
      Vaccinium arctostaphylos has beneficial effects on serum lipid profile and
      oxidative stress in hyperlipidemic adult patients. Therefore, it could be
      considered as a supplement for treatment of dyslipidemia and prevention of
      atherosclerosis development. 

PMID- 24587808
TI  - Application of complementary and alternative medicine on neurodegenerative
      disorders 2013.

PMID- 24587809
TI  - Preparation of the Branch Bark Ethanol Extract in Mulberry Morus alba, Its
      Antioxidation, and Antihyperglycemic Activity In Vivo.
AB  - The biological activities of the branch bark ethanol extract (BBEE) in the
      mulberry Morus alba L. were investigated. The determination of active component
      showed that the flavonoids, phenols, and saccharides are the major components of
      the ethanol extract. The BBEE had a good scavenging activity of the 1,1-diphenyl
      2-picrylhydrazyl (DPPH) radical with around 100  MU g/mL of IC50 value. In vitro
      assay revealed that the BBEE strongly inhibited both alpha -glucosidase and
      sucrase activities whose IC50 values were 8.0 and 0.24  MU g/mL, respectively.
      The kinetic analysis showed that the BBEE as a kind of alpha -glucosidase
      inhibitor characterized a competitive inhibition activity. Furthermore, the
      carbohydrate tolerance of the normal mice was obviously enhanced at 0.5 h (P <
      0.05) and 1.0 h (P < 0.05) after the BBEE intragastric administration as compared
      to negative control. At 0.5, 1.0, 1.5, and 2.0 h after the intragastric
      administration with starch, the postprandial hyperglycemia of the type 2 diabetic
      mice can be significantly decreased (P < 0.01) by supplying various
      concentrations of the BBEE (10-40 mg/kg body weight). Therefore, the BBEE could
      effectively inhibit the postprandial hyperglycemia as a novel alpha -glucosidase
      activity inhibitor for the diabetic therapy. 

PMID- 24587810
TI  - Medical ethnobiology and ethnopharmacology in latin america 2013.

PMID- 24587811
TI  - Anticancer effect of fucoidan in combination with tyrosine kinase inhibitor
      lapatinib.
AB  - Background. Despite a number of in vitro and in vivo studies reporting the
      efficacy of fucoidan in treating various cancers, few studies have measured the
      efficacy of dietary fucoidan (DF) in combination with cancer drugs. Thus, we
      examined the sensitivity of DF in combination with the EGFR/ERBB2-targeting
      reagent lapatinib on cancer cells. Method. We selected six EGFR/ERBB2-amplified
      cancer cell lines (OE19, NCI-N87, OE33, ESO26, MKN7, and BT474) as an in vitro
      model and tested their sensitivity to DF alone and to DF in combination with the
      well-known EGFR/ERBB2-targeting reagent lapatinib. Result. Overall, in drug
      independent sensitivity test, DF alone did not significantly inhibit the growth
      of EGFR/ERBB2-amplified cancer cells in vitro. When DF was given in combination
      with lapatinib, however, it tended to synergistically inhibit cell growth in OE33
      but antagonized the action of lapatinib in ESO26, NCI-N87, and OE19. Conclusion.
      This study suggests that DF has the potential to increase or decrease the effects
      of certain anticancer drugs on certain cancer cell types. Further study is needed
      to explore the mechanism of interaction and synergistic antitumor activity of DF
      in combination with chemotherapy and targeted therapy. 

PMID- 24587812
TI  - Neuro-immune-endocrine functions of the skin: an overview.

PMID- 24587813
TI  - IL-15 Agonists: The Cancer Cure Cytokine.
AB  - The immune stimulatory cytokine interleukin-15 was recognized as one of the most
      promising cancer cure drug in an NIH guided review and is currently in clinical
      trial alone or as an adjuvant for certain types of metastatic solid tumors. IL-15
      is an essential survival factor for natural killer (NK), natural killer-like T
      (NKT), and CD44hi memory CD8 T cells. The bioactivity of IL-15 in vivo is
      conferred mainly through a trans-presentation mechanism in which IL-15 is
      presented in complex with the alpha-subunit of soluble IL-15 receptor (IL-15R) to
      NK, NKT or T cells rather than directly interacts with membrane-bound IL-15R.
      With these understandings, recent studies have been focused on generating IL-15
      agonists which consist of IL-15 and partial or whole of soluble IL-15R to improve
      its in vivo bioactivity. This minireview will summarize the key features of IL-15
      as a potential cancer treatment cytokine and the most recent development of IL-15
      agonists and preclinical studies. Critical milestones to translate the pre
      clinical development to in-patients treatment are emphasized.

PMID- 24587814
TI  - Left ventricular endocardium tracking by fusion of biomechanical and deformable
      models.
AB  - This paper presents a framework for tracking left ventricular (LV) endocardium
      through 2D echocardiography image sequence. The framework is based on fusion of
      biomechanical (BM) model of the heart with the parametric deformable model. The
      BM model constitutive equation consists of passive and active strain energy
      functions. The deformations of the LV are obtained by solving the constitutive
      equations using ABAQUS FEM in each frame in the cardiac cycle. The strain energy
      functions are defined in two user subroutines for active and passive phases.
      Average fusion technique is used to fuse the BM and deformable model contours.
      Experimental results are conducted to verify the detected contours and the
      results are evaluated by comparing them to a created gold standard. The results
      and the evaluation proved that the framework has the tremendous potential to
      track and segment the LV through the whole cardiac cycle.

PMID- 24587815
TI  - Differentiating small (<=1 cm) focal liver lesions as metastases or cysts by
      means of computed tomography: a case-study to illustrate a fuzzy logic-based
      method to assess the impact of diagnostic confidence on radiological diagnosis.
AB  - PURPOSE: To quantify the impact of diagnostic confidence on radiological
      diagnosis with a fuzzy logic-based method. MATERIALS AND METHODS: Twenty-two
      oncologic patients with 20 cysts and 30 metastases <=1 cm in size found at 64-row
      computed tomography were included. Two readers (R1/R2) expressed diagnoses as a
      subjective level of confidence P(d) in malignancy within the interval [0,1]
      rather than on a "crisp" basis (malignant/benign); confidence in benignancy was 1
      - p(d). When cross-tabulating data according to the standard of reference, 2 * 2
      table cells resulted from the aggregation between p(d)/1 - p(d) and final
      diagnosis. We then assessed (i) readers diagnostic performance on a fuzzy and
      crisp basis; (ii) the "divergence" delta(F, C) (%) as a measure of how confidence
      impacted on crisp diagnosis. RESULTS: Diagnoses expressed with lower confidence
      increased fuzzy false positives compared to crisp ones (from 0 to 0.2 for R1;
      from 1 to 2.4 for R2). Crisp/fuzzy accuracy was 94.0%/93.6% (R1) and 94.0/91.6%
      (R2). delta(F, C) (%) was larger in the case of the less experienced reader (R2)
      (up to +7.95% for specificity). According to simulations, delta(F, C) (%) was
      negative/positive depending on the level of confidence in incorrect diagnoses.
      CONCLUSION: Fuzzy evaluation shows a measurable effect of uncertainty on
      radiological diagnoses.

PMID- 24587816
TI  - Integrative approaches in computational biomedical imaging 2013.

PMID- 24587817
TI  - On multilabel classification methods of incompletely labeled biomedical text
      data.
AB  - Multilabel classification is often hindered by incompletely labeled training
      datasets; for some items of such dataset (or even for all of them) some labels
      may be omitted. In this case, we cannot know if any item is labeled fully and
      correctly. When we train a classifier directly on incompletely labeled dataset,
      it performs ineffectively. To overcome the problem, we added an extra step,
      training set modification, before training a classifier. In this paper, we try
      two algorithms for training set modification: weighted k-nearest neighbor (WkNN)
      and soft supervised learning (SoftSL). Both of these approaches are based on
      similarity measurements between data vectors. We performed the experiments on
      AgingPortfolio (text dataset) and then rechecked on the Yeast (nontext genetic
      data). We tried SVM and RF classifiers for the original datasets and then for the
      modified ones. For each dataset, our experiments demonstrated that both
      classification algorithms performed considerably better when preceded by the
      training set modification step. 

PMID- 24587818
TI  - Antibiotic use as a tragedy of the commons: a cross-sectional survey.
AB  - BACKGROUND: Many believe antibiotic use results in a tragedy of the commons,
      since overuse may lead to antibiotic resistance and limiting use would benefit
      society. In contrast, mass antibiotic treatment programs are thought to result in
      community-wide benefits. A survey was conducted to learn the views of infectious
      disease experts on the individual- and societal-level consequences of antibiotic
      use. METHODS: The survey instrument was designed to elicit opinions on antibiotic
      use and resistance. It was sent via SurveyMonkey to infectious disease
      professionals identified through literature searches. Descriptive statistics were
      used to analyze the data. RESULTS: A total of 1,530 responses were received for a
      response rate of 9.9%. Nearly all participants believed antibiotic use could
      result in a tragedy of the commons, at least in certain circumstances (96.0%).
      Most participants did not believe mass antibiotic treatment programs could
      produce societal benefits in an antibiotic-free society (91.4%) or in the United
      States (94.2%), though more believed such programs would benefit antibiotic-free
      societies compared to the United States (P < 0.001). CONCLUSIONS: The experts
      surveyed believe that antibiotic use can result in a tragedy of the commons and
      do not believe that mass treatment programs benefit individuals or society.

PMID- 24587819
TI  - A randomized trial of a fully covered self-expandable metallic stent versus
      plastic stents in anastomotic biliary strictures after liver transplantation.
AB  - BACKGROUND: Post-liver-transplant biliary anastomotic strictures (ASs) are
      currently managed with repeated endoscopic retrograde cholangiopancreatographies
      (ERCPs) inserting multiple plastic stents. Fully covered self-expanding metal
      stents (FCSEMSs) are being increasingly reported in the management of this
      condition, however no prospective randomized trials have been performed to date.
      AIM: The aim of this study was to determine whether FCSEMSs decrease overall
      numbers of ERCPs needed to achieve stricture resolution and to establish the
      safety, efficacy and cost-effectiveness in this setting. METHODS: Two tertiary
      referral centres performed this open-label prospective randomized trial. A total
      of 32 patients consented and subsequently 20 were randomized with 10 in the
      FCSEMS arm and 10 in the plastic arm. The FCSEMS arm had the stent in situ for 12
      weeks with the plastic stent arm undergoing 3-monthly multiple plastic stenting
      with or without dilatation over a year. RESULTS: The median number of ERCPs
      performed per patient in the FCSEMS was 2 versus 4.5 (p = 0.0001) in the plastic
      stenting arm. Stricture resolution was achieved in all 10 patients with FCSEMSs
      compared with 8/10 in the plastic arm [p = not significant (NS)]. Complications
      occurred in 1/10 patients in the FCSEMS arm versus 5/10 in the plastic arm (p =
      0.051). Days in hospital for complications was 6 in the FCSEMS versus 56 in the
      plastic arm (p = 0.11). Cost analysis shows that the FCSEMS arm was more cost
      effective. No cases of FCSEMS migration were seen. CONCLUSIONS: FCSEMSs reduced
      the number of ERCPs needed to achieve stricture resolution with similar
      recurrence rates between arms. The FCSEMSs may do so with fewer complications
      making it cost effective.

PMID- 24587821
TI  - The role of capsule endoscopy in acute gastrointestinal bleeding.
AB  - Acute gastrointestinal (GI) bleeding is a common cause of hospitalization,
      resulting in about 400,000 hospital admissions annually, with a mortality rate of
      5-10%. It is estimated that 5% of acute GI bleedings are of obscure origin with a
      normal esophagogastroduodenoscopy and ileocolonoscopy. Capsule endoscopy is the
      state-of-the-art procedure for inspection of the entire small bowel with a high
      sensitivity for the detection of causes of bleeding. In recent years, many
      studies have addressed the sensitivity and outcome of capsule-endoscopy
      procedures in patients with acute GI bleeding. This review looks at the role of
      capsule endoscopy in the evaluation of patients with acute GI bleeding from
      either the upper GI tract or small bowel. 

PMID- 24587822
TI  - Endoscopic ultrasound-guided hepatic and perihepatic abscess drainage: an
      evolving technique.
AB  - Interventional radiology-guided percutaneous drainage of liver abscesses with
      concomitant use of antibiotics has been the conventional approach for the
      treatment of liver abscesses. Hepatic abscesses refractory or not amenable to
      percutaneous drainage have been treated with surgical drainage, either via
      laparoscopic or open laparotomy techniques. The aim of this review was to
      evaluate the technical feasibility and efficacy of endoscopic ultrasound (EUS)
      guided drainage of liver abscesses. A literature review was performed to identify
      the studies describing the technique. In this review article we have summarized
      case series or reports describing EUS-guided liver abscess drainage. The
      indications, techniques, endoprostheses, limitations and complications reported
      are discussed. A total of seven cases have been described so far in the
      literature which included patients with failed conventional treatment modalities.
      The EUS-guided drainage technique involves puncturing the abscess using
      endosonography to gain access, passing a guidewire followed by tract dilation and
      placement of an endoprosthesis for drainage. Studies have reported 100% technical
      and clinical success rates in selected cases. No complications were reported. EUS
      guided drainage of liver abscesses can be a safe and effective alternative
      approach in the management of liver abscesses in selected patients. 

PMID- 24587820
TI  - Clostridium difficile infection: management strategies for a difficult disease.
AB  - Clostridium difficile was first described as a cause of diarrhea in 1978 and in
      the last three decades has reached an epidemic state with increasing incidence
      and severity in both healthcare and community settings. There also has been a
      rise in severe outcomes from C. difficile infection (CDI). There have been
      tremendous advancements in the field of CDI with the identification of newer risk
      factors, recognition of CDI in populations previously thought not at risk and
      development of better diagnostic modalities. Several treatment options are
      available for CDI apart from metronidazole and vancomycin, and include new drugs
      such as fidaxomicin and other options such as fecal microbiota transplantation.
      This review discusses the epidemiology, risk factors and outcomes from CDI, and
      focuses primarily on existing and evolving treatment modalities. 

PMID- 24587823
TI  - Immunoglobulin therapy for refractory Crohn's disease.

PMID- 24587824
TI  - Tolcapone addition improves Parkinson's disease associated nonmotor symptoms.
AB  - BACKGROUND: Addition of catechol-O-methyltransferase inhibitors to a conventional
      levodopa/dopadecarboxylase inhibitor regimen improves motor symptoms in patients
      with Parkinson's disease. Optimizing dopamine substitution is also beneficial for
      nonmotor features. OBJECTIVES: To investigate the efficacy of supplemental
      tolcapone intake on nonmotor symptoms. DESIGN/METHODS: A total of 125 levodopa
      treated patients additionally took tolcapone in this observational trial.
      Initially and following 4 weeks of tolcapone intake, the neurologist scored with
      Unified Parkinson's Disease Rating Scale parts I, II, IV, the nonmotor symptoms
      scale for Parkinson's disease and recorded the off time. The patients rated
      themselves with the EuroQuol, its visual analogue scale and the nonmotor
      screening questionnaire. Caregivers reported the daily duration of care giving.
      RESULTS: All scores improved except for Unified Parkinson's Disease Rating Scale
      part IV and domains 4, 5 and 8 of the nonmotor symptoms scale for Parkinson's
      disease. CONCLUSION: This trial demonstrates that tolcapone addition may improve
      nonmotor features.

PMID- 24587825
TI  - Mechanisms of action of ACTH in the management of relapsing forms of multiple
      sclerosis.
AB  - Acute and subacute inflammation, the mechanisms by which demyelination and axonal
      loss occur in multiple sclerosis (MS), result from the migration of activated
      immune cells into the central nervous system parenchyma. The triggering antigen
      is unknown, but the process involves deregulated immune response of T and B
      lymphocytes, macrophages, and mediators with expansion of autoreactive T cells
      creating a shift in the balance of pro- and anti-inflammatory cytokines favoring
      inflammation. Ongoing disease activity and exacerbations early in the course of
      relapsing-remitting MS may prevent full remission and propagate future
      progressive disability. A key strategy of immune therapy is timely initiation of
      treatment to achieve remission, followed by maintenance of remission. In this
      context, treatment with high-dose methylprednisolone (MP) is currently
      recommended to induce a faster recovery from a clinical exacerbation that results
      from an acute inflammatory attack. Adrenocorticotropic hormone (ACTH or
      corticotropin) gel is an alternative for patients who do not respond to or do not
      tolerate corticosteroids. ACTH is a universal agonist in the melanocortin (MC)
      system and, as such, among other functions, stimulates the adrenal cortex to
      produce cortisol. MCs are a family of peptides that includes ACTH and other MC
      peptides. This system has five classes of receptors, all of which show a strong
      affinity for ACTH, suggesting a more complex and dynamic mechanism than only
      inducing endogenous corticosteroid production. ACTH and MCs regulate processes
      relevant to MS, including anti-inflammatory and immunomodulatory functions
      involving lymphocytes, macrophages, the sympathetic nervous system involved in
      inflammatory processes, and reduction of pro-inflammatory cytokines. The clinical
      implications of the mechanistic differences between corticosteroid and ACTH gel
      treatment remain to be elucidated. Recent data show that patients experiencing an
      acute exacerbation, who previously had suboptimal response to or were unable to
      tolerate MP treatment, showed positive clinical outcomes with fewer adverse
      events with ACTH gel. 

PMID- 24587826
TI  - 4-Aminopyridine for symptomatic treatment of multiple sclerosis: a systematic
      review.
AB  - This systematic review summarizes the existing evidence on the effect of 4
      aminopyridine (4-AP) as a symptomatic treatment of decreased walking capacity in
      patients with multiple sclerosis (MS) when administered as an immediate release
      compound and a slow release compound. It summarizes existing evidence on the
      basic mechanisms of 4-AP from experimental studies and evidence on the clinical
      use of the compound. A systematic literature search was conducted of the
      following databases: PubMed and EMBASE. Thirty-five studies were included in the
      review divided into 16 experimental studies, two clinical studies with
      paraclinical endpoints and 17 clinical studies with clinical endpoints. Animal
      studies show that 4-AP can improve impulse conduction through demyelinated
      lesions. In patients with MS this translates into improved walking speed and
      muscle strength of the lower extremities in a subset of patients at a level that
      is often of clinical relevance. Phase III trials demonstrate approximately 25%
      increase in walking speed in roughly 40% and improved muscle strength in the
      lower extremities. Furthermore, 4-AP might have an effect on other domains such
      as cognition, upper extremity function and bowel and bladder, but this warrants
      further investigation. Side effects are mainly mild to moderate, consisting
      primarily of paraesthesia, dizziness, nausea/vomiting, falls/balance disorders,
      insomnia, urinary tract infections and asthenia. Side effects are worse when
      administered intravenously and when administered as an immediate release
      compound. Serious adverse events are rarely seen in the marketed clinical
      dosages. In conclusion, 4-AP is easy and safe to use. Slow release 4-AP shows
      more robust clinical effects and a more beneficial side-effect profile than
      immediate release 4-AP. 

PMID- 24587827
TI  - Chronic cerebrospinal venous insufficiency and multiple sclerosis: a
      comprehensive meta-analysis of case-control studies.
AB  - OBJECTIVES: Chronic cerebrospinal venous insufficiency (CCSVI) has recently been
      implicated in the pathogenesis of multiple sclerosis (MS). This comprehensive
      meta-analysis of case-control studies investigates the association of CCSVI with
      MS. METHODS: Through Medline, EMBASE and Cochrane database searches, case-control
      ultrasound studies comparing CCSVI frequency among patients with MS and healthy
      controls were identified. RESULTS: We identified 19 eligible studies including
      1250 patients with MS and 899 healthy controls. The pooled analysis showed that
      CCSVI was associated with MS [odds ratio (OR) 8.35; 95% confidence interval (CI)
      3.44-20.31; p < 0.001) with considerable heterogeneity across studies (I (2) =
      80.1%). This association was substantially attenuated in sensitivity analyses
      excluding studies that were carried out by the group that originally described
      CCSVI, included investigators who had also been involved in publications
      advocating endovascular procedures for CCSVI treatment, or were conducted in
      Italy. Our most conservative sensitivity analysis combining different exclusion
      criteria yielded no association of CCSVI with MS (OR 1.35; 95% CI 0.62-2.93; p =
      0.453) without any heterogeneity (I (2) = 0%). CONCLUSION: There is considerable
      heterogeneity across different case-control studies evaluating the association of
      CCSVI and MS. The greatest factor contributing to this heterogeneity appears to
      be the involvement of investigators in other publications supporting endovascular
      procedures as a novel MS treatment.

PMID- 24587829
TI  - The efficacy of second-line hormone therapy for recurrence during adjuvant
      hormone therapy for breast cancer.
AB  - OBJECTIVES: The recurrence of breast cancer during adjuvant hormone therapy is
      often targeted by second-line hormone therapy. However, there has been a lack of
      prior success with such treatments. We retrospectively investigated the efficacy
      of subsequent hormone therapy. METHODS: Patients who underwent breast cancer
      surgery between 2006 and 2012 at our institution were investigated. RESULTS: A
      total of 20 patients developed recurrence during adjuvant hormone therapy. There
      were four patients with luminal A, seven with luminal B and six with luminal HER2
      tumors, respectively. Twelve patients received subsequent hormone therapy, and
      eight patients received chemotherapy. Subsequent hormone therapy produced one
      partial response (PR), two long stable disease (SD), one SD and five progressive
      disease (PD). A clinical benefit (CB) was obtained by 33%. Subsequent
      chemotherapy produced one complete response (CR), two PRs, one long SD and two
      PD, resulting in a CB in 66%. Among those who received any hormone therapy, the
      best responses were two PR, three long SD and one SD. A CB was obtained by 38%,
      while seven patients did not have any CB from hormone therapy. Meanwhile, the
      best responses to chemotherapy were two CRs, four PRs, three SD and two PD, thus
      resulting in a CB in 72%. All luminal A cases obtained a long SD or SD with
      hormone therapy. However, the CB of hormone therapy for non-luminal A cases was
      only 30%. CONCLUSIONS: The efficacy of hormone therapy for recurrence during
      adjuvant hormone therapy is poor, and when selecting therapy for such patients,
      the breast cancer subtype should be taken into account.

PMID- 24587828
TI  - Specific aspects of modern life for people with multiple sclerosis:
      considerations for the practitioner.
AB  - Multiple sclerosis (MS) is a chronic, debilitating, neurodegenerative disease
      that has a high impact on patients' quality of life. Individuals are often
      diagnosed in early adulthood and are faced with the difficulty of managing their
      lifestyle within the context of this chronic illness. Here we review factors that
      influence the disease course and the challenges that might be encountered when
      managing patients with MS. The majority of diagnosed patients are women of
      childbearing age, making pregnancy-related issues a key concern. MS typically
      stabilizes during pregnancy and evidence suggests that the disease has no impact
      on the risk of complications or outcomes. However, the effect of disease
      modifying therapies on outcomes is less clear, and discontinuation of treatment
      prior to pregnancy or when breastfeeding is recommended. Awareness of genetic
      risk factors is important for patients planning a family, as several genes
      increase the risk of MS. Further aspects that require consideration include
      infections, vaccinations, environmental factors, surgery and the emergence of
      osteoporosis. Vaccinations are generally not a risk factor for MS and may be
      beneficial in terms of protection against infection and reducing the number of
      relapses. Environmental factors such as vitamin D deficiency, low exposure to
      sunlight, smoking and Epstein-Barr virus infection can all negatively influence
      the disease course. Furthermore, osteoporosis is generally higher in patients
      with MS than the general population, and the risk is increased by the
      environmental and genetic factors associated with the disease; bone mineral
      density should be assessed and smoking cessation and correction of serum vitamin
      D levels are recommended. Finally, as patients with MS are typically young, they
      are at low risk of surgery-related complications, although they should be
      carefully monitored postoperatively. Awareness of, and planning around, these
      factors may minimize the impact of the disease on patients' lifestyle. 

PMID- 24587830
TI  - Tumor heterogeneity in the clinic: is it a real problem?
AB  - Tumor heterogeneity is one of the major problems limiting the efficacy of
      targeted therapies and compromising treatment outcomes. A better understanding of
      tumor biology has advanced our knowledge of the molecular landscape of cancer to
      an unprecedented level. However, most patients with advanced cancers treated with
      appropriately selected targeted therapies become resistant to the therapy,
      ultimately developing disease progression and succumbing to metastatic disease.
      Multiple factors account for therapeutic failures, which include cancer cells
      accumulating new molecular aberrations as a consequence of tumor progression and
      selection pressure of cancer therapies. Therefore, single agent targeted
      therapies, often administered in advanced stages, are unlikely to have a
      sufficiently lethal effect in most cancers. Finally, the molecular profile of
      cancer can change over time, which we are not able to monitor with existing
      strategies using tumor tissue biopsies as the gold standard for molecular
      diagnostics. Novel technologies focusing on testing low-risk, easily obtainable
      material, such as molecular cell-free DNA from plasma, can fill that gap and
      allow personalized therapy to be delivered in real time. 

PMID- 24587831
TI  - Anti-inflammatory/antioxidant use in long-term maintenance cancer therapy: a new
      therapeutic approach to disease progression and recurrence.
AB  - The chronic, progressive clinical characteristics of many adult solid tumor
      malignancies suggest that a more effective therapeutic approach to cancer
      management may require long-term intervention using nontoxic systemic agents that
      block critical components of abnormal tumor physiology. Two highly promising
      systemic targets common to the development, progression and recurrence of many
      common cancers are dysregulated inflammatory and oxidation/reduction (redox)
      pathways. Compelling clinical data support the use of anti-inflammatory and
      antioxidant agents as a therapeutic modality for long-term use in patients
      diagnosed with several common cancers, including colon cancer and breast cancer.
      The therapeutic paradigm presented in this paper is the product of a synthesis of
      what is currently understood about the biological effects of inflammation and
      oxidative stress that contribute to tumorigenesis, disease progression and
      recurrence as well as results obtained from research on the use of prophylactics
      with anti-inflammatory or antioxidant properties in cancer prevention and
      treatment. 

PMID- 24587833
TI  - New perspectives on duality of patterning: Introduction to the special issue.

PMID- 24587832
TI  - Relapsed small cell lung cancer: treatment options and latest developments.
AB  - According to recent analyses, there was a modest yet significant improvement in
      median survival time and 5-year survival rate of limited stage small cell lung
      cancer (SCLC) in North America, Europe, Japan and other countries over the last
      30 years. The median survival time of limited stage SCLC is 15-20 months and 5
      year survival rate is 15% or less. In terms of extensive stage SCLC, a median
      survival time of 9.4-12.8 months and 2-year survival of 5.2-19.5% are still
      disappointing. Despite being highly sensitive to first-line chemotherapy and
      radiotherapy treatments, most patients with SCLC experience relapse within 2
      years and die from systemic metastasis. While several clinical trials of
      cytotoxic chemotherapies and molecular targeting agents have been investigated in
      the treatment of relapsed SCLC, none showed a significant clinical activity to be
      able to exceed topotecan as second-line chemotherapy. There are problematic
      issues to address for relapsed SCLC, such as standardizing the treatment for
      third-line chemotherapy. Topotecan alone was the first approved therapy for
      second-line treatment for relapsed SCLC. Amrubicin is a promising drug and a
      variety of trials evaluating its efficacy have been carried out. Amrubicin has
      shown superiority to topotecan in a Japanese population, but was not superior in
      a study of western patients. There are some controversial issues for relapsed
      SCLC, such as treatment for older patients, third-line chemotherapy and efficacy
      of molecular targeting therapy. This article reviews current standard treatment,
      recent clinical trials and other topics on relapsed SCLC. 

PMID- 24587834
TI  - Continuous heliox breathing and the extent of anatomic zone of noreflow and
      necrosis following ischemia/reperfusion in the rabbit heart.
AB  - BACKGROUND: Nitrogen may contribute to reperfusion injury. Some studies have
      shown that helium as a replacement for nitrogen in breathing gas (heliox) reduces
      cell necrosis after ischemia/reperfusion when used in a preconditioning fashion
      (intermittent heliox exposure). Our aim was to test whether heliox, breathed
      continuously throughout the ischemic and reperfusion periods, reduced necrosis
      and a marker of reperfusion injury, the no-reflow phenomenon. METHODS AND
      RESULTS: Anesthetized, open-chest rabbits received 30 min coronary artery
      occlusion/3 hrs reperfusion. Before CAO rabbits were randomized to heliox (30%
      oxygen + 70% helium, n=8) or air supplemented with oxygen to achieve blood gas
      values within physiologic range (n = 8). Rabbits received the appropriate mix
      during ischemic and reperfusion periods. Infarct size (% risk zone) and no-reflow
      defect were measured at the end of the reperfusion period. The ischemic risk zone
      was similar in both groups (28% of left ventricle in heliox and 29% in control).
      Heliox breathing did not reduce necrosis; infarct size, expressed as a percentage
      of the risk region was 44+/-4% in the heliox group and 49+/-5% in controls, p =
      0.68. The extent of the no-reflow defect was not altered by heliox, either
      expressed as a percent of the risk region (29+/-4% in heliox and 28+/-3% in
      control) or as a percent of the necrotic zone (65+/-5% in heliox and 59+/-8% in
      control).Heliox treatment had no effect on hemodynamic parameters or arterial
      blood gas values. CONCLUSION: Continuous heliox breathing does not appear to be
      cardioprotective in the setting of acute myocardial infarction in the rabbit
      model. Heliox respiration administered during 30 minutes of ischemia and 180
      minutes of reperfusion did not alter infarct size or the extent of no-reflow.

PMID- 24587835
TI  - Analysis of auto-aligned and auto-segmented oral discourse by speakers with
      aphasia: A preliminary study on the acoustic parameter of duration.

PMID- 24587837
TI  - Evaluation of transient osteoporosis of the hip in magnetic resonance imaging.
AB  - Transient osteoporosis is a relatively rare condition of unknown etiology that
      causes temporary bone loss. The syndrome is characterized by self-limited course
      and spontaneous resolution after 6 to 12 months. The pathogenesis of transient
      osteoporosis is not fully understood but several hypotheses that have been
      proposed include trauma, neurovascular dysfunction and transient hyperemia.
      Clinical manifestations include sudden onset of pain in the hip that usually
      worsens with weight bearing and leads to functional disability involving the
      affected extremity. Radiographs are frequently unremarkable, but may reveal
      periarticular osteopenia 3-6 weeks after the onset of clinical symptoms. There is
      no radiographic evidence of demineralization during the early phase of syndrome,
      as a result advanced imaging is required. Magnetic resonance imaging is the most
      sensitive and predictable test for an early diagnosis and monitoring of disease
      progression. 

PMID- 24587836
TI  - beta-Defensin Genomic Copy Number Does Not Influence the Age of Onset in
      Huntington's Disease.
AB  - BACKGROUND: Huntington's disease (HD) is an autosomal dominant neurodegenerative
      disorder caused by the abnormal expansion of a CAG triplet repeat tract in the
      huntingtin gene. While the length of this CAG expansion is the major determinant
      of the age of onset (AO), other genetic factors have also been shown to play a
      modulatory role. Recent evidence suggests that neuroinflammation is a pivotal
      factor in the pathogenesis of HD, and that targeting this process may have
      important therapeutic ramifications. The human beta-defensin 2 (hBD2) - encoded
      by DEFB4 - is an antimicrobial peptide that exhibits inducible expression in
      astrocytes during inflammation and is an important regulator of innate and
      adaptive immune response. Therefore, DEFB4 may contribute to the
      neuroinflammatory processes observed in HD. OBJECTIVE: In this study we tested
      the hypothesis that copy number variation (CNV) of the beta-defensin region,
      including DEFB4, modifies the AO in HD. METHODS AND RESULTS: We genotyped beta
      defensin CNV in 490 HD individuals using the paralogue ratio test and found no
      association between beta-defensin CNV and onset of HD. CONCLUSIONS: We conclude
      that it is unlikely that DEFB4 plays a role in HD pathogenesis.

PMID- 24587838
TI  - RANKING RELATIONS USING ANALOGIES IN BIOLOGICAL AND INFORMATION NETWORKS.
AB  - Analogical reasoning depends fundamentally on the ability to learn and generalize
      about relations between objects. We develop an approach to relational learning
      which, given a set of pairs of objects S = {A(1) : B(1), A(2) : B(2), ..., A(N) :
      B(N)}, measures how well other pairs A : B fit in with the set S. Our work
      addresses the following question: is the relation between objects A and B
      analogous to those relations found in S? Such questions are particularly relevant
      in information retrieval, where an investigator might want to search for
      analogous pairs of objects that match the query set of interest. There are many
      ways in which objects can be related, making the task of measuring analogies very
      challenging. Our approach combines a similarity measure on function spaces with
      Bayesian analysis to produce a ranking. It requires data containing features of
      the objects of interest and a link matrix specifying which relationships exist;
      no further attributes of such relationships are necessary. We illustrate the
      potential of our method on text analysis and information networks. An application
      on discovering functional interactions between pairs of proteins is discussed in
      detail, where we show that our approach can work in practice even if a small set
      of protein pairs is provided.

PMID- 24587839
TI  - SPARSE INTEGRATIVE CLUSTERING OF MULTIPLE OMICS DATA SETS.
AB  - High resolution microarrays and second-generation sequencing platforms are
      powerful tools to investigate genome-wide alterations in DNA copy number,
      methylation, and gene expression associated with a disease. An integrated genomic
      profiling approach measuring multiple omics data types simultaneously in the same
      set of biological samples would render an integrated data resolution that would
      not be available with any single data type. In this study, we use penalized
      latent variable regression methods for joint modeling of multiple omics data
      types to identify common latent variables that can be used to cluster patient
      samples into biologically and clinically relevant disease subtypes. We consider
      lasso (Tibshirani, 1996), elastic net (Zou and Hastie, 2005), and fused lasso
      (Tibshirani et al., 2005) methods to induce sparsity in the coefficient vectors,
      revealing important genomic features that have significant contributions to the
      latent variables. An iterative ridge regression is used to compute the sparse
      coefficient vectors. In model selection, a uniform design (Fang and Wang, 1994)
      is used to seek "experimental" points that scattered uniformly across the search
      domain for efficient sampling of tuning parameter combinations. We compared our
      method to sparse singular value decomposition (SVD) and penalized Gaussian
      mixture model (GMM) using both real and simulated data sets. The proposed method
      is applied to integrate genomic, epigenomic, and transcriptomic data for subtype
      analysis in breast and lung cancer data sets.

PMID- 24587840
TI  - BAYESIAN SEMIPARAMETRIC ANALYSIS FOR TWO-PHASE STUDIES OF GENE-ENVIRONMENT
      INTERACTION.
AB  - The two-phase sampling design is a cost-efficient way of collecting expensive
      covariate information on a judiciously selected sub-sample. It is natural to
      apply such a strategy for collecting genetic data in a sub-sample enriched for
      exposure to environmental factors for gene-environment interaction (G * E)
      analysis. In this paper, we consider two-phase studies of G * E interaction where
      phase I data are available on exposure, covariates and disease status. Stratified
      sampling is done to prioritize individuals for genotyping at phase II conditional
      on disease and exposure. We consider a Bayesian analysis based on the joint
      retrospective likelihood of phase I and phase II data. We address several
      important statistical issues: (i) we consider a model with multiple genes,
      environmental factors and their pairwise interactions. We employ a Bayesian
      variable selection algorithm to reduce the dimensionality of this potentially
      high-dimensional model; (ii) we use the assumption of gene-gene and gene
      environment independence to trade-off between bias and efficiency for estimating
      the interaction parameters through use of hierarchical priors reflecting this
      assumption; (iii) we posit a flexible model for the joint distribution of the
      phase I categorical variables using the non-parametric Bayes construction of
      Dunson and Xing (2009). We carry out a small-scale simulation study to compare
      the proposed Bayesian method with weighted likelihood and pseudo likelihood
      methods that are standard choices for analyzing two-phase data. The motivating
      example originates from an ongoing case-control study of colorectal cancer, where
      the goal is to explore the interaction between the use of statins (a drug used
      for lowering lipid levels) and 294 genetic markers in the lipid
      metabolism/cholesterol synthesis pathway. The sub-sample of cases and controls on
      which these genetic markers were measured is enriched in terms of statin users.
      The example and simulation results illustrate that the proposed Bayesian approach
      has a number of advantages for characterizing joint effects of genotype and
      exposure over existing alternatives and makes efficient use of all available data
      in both phases.

PMID- 24587841
TI  - REFINING GENETICALLY INFERRED RELATIONSHIPS USING TREELET COVARIANCE SMOOTHING.
AB  - Recent technological advances coupled with large sample sets have uncovered many
      factors underlying the genetic basis of traits and the predisposition to complex
      disease, but much is left to discover. A common thread to most genetic
      investigations is familial relationships. Close relatives can be identified from
      family records, and more distant relatives can be inferred from large panels of
      genetic markers. Unfortunately these empirical estimates can be noisy, especially
      regarding distant relatives. We propose a new method for denoising genetically
      inferred relationship matrices by exploiting the underlying structure due to
      hierarchical groupings of correlated individuals. The approach, which we call
      Treelet Covariance Smoothing, employs a multiscale decomposition of covariance
      matrices to improve estimates of pairwise relationships. On both simulated and
      real data, we show that smoothing leads to better estimates of the relatedness
      amongst distantly related individuals. We illustrate our method with a large
      genome-wide association study and estimate the "heritability" of body mass index
      quite accurately. Traditionally heritability, defined as the fraction of the
      total trait variance attributable to additive genetic effects, is estimated from
      samples of closely related individuals using random effects models. We show that
      by using smoothed relationship matrices we can estimate heritability using
      population-based samples. Finally, while our methods have been developed for
      refining genetic relationship matrices and improving estimates of heritability,
      they have much broader potential application in statistics. Most notably, for
      error-in-variables random effects models and settings that require regularization
      of matrices with block or hierarchical structure.

PMID- 24587842
TI  - Extreme value analysis for evaluating ozone control strategies.
AB  - Tropospheric ozone is one of six criteria pollutants regulated by the US EPA, and
      has been linked to respiratory and cardiovascular endpoints and adverse effects
      on vegetation and ecosystems. Regional photochemical models have been developed
      to study the impacts of emission reductions on ozone levels. The standard
      approach is to run the deterministic model under new emission levels and
      attribute the change in ozone concentration to the emission control strategy.
      However, running the deterministic model requires substantial computing time, and
      this approach does not provide a measure of uncertainty for the change in ozone
      levels. Recently, a reduced form model (RFM) has been proposed to approximate the
      complex model as a simple function of a few relevant inputs. In this paper, we
      develop a new statistical approach to make full use of the RFM to study the
      effects of various control strategies on the probability and magnitude of extreme
      ozone events. We fuse the model output with monitoring data to calibrate the RFM
      by modeling the conditional distribution of monitoring data given the RFM using a
      combination of flexible semiparametric quantile regression for the center of the
      distribution where data are abundant and a parametric extreme value distribution
      for the tail where data are sparse. Selected parameters in the conditional
      distribution are allowed to vary by the RFM value and the spatial location. Also,
      due to the simplicity of the RFM, we are able to embed the RFM in our Bayesian
      hierarchical framework to obtain a full posterior for the model input parameters,
      and propagate this uncertainty to the estimation of the effects of the control
      strategies. We use the new framework to evaluate three potential control
      strategies, and find that reducing mobile-source emissions has a larger impact
      than reducing point-source emissions or a combination of several emission
      sources.

PMID- 24587843
TI  - Macroeconomic effects on mortality revealed by panel analysis with nonlinear
      trends.
AB  - Many investigations have used panel methods to study the relationships between
      fluctuations in economic activity and mortality. A broad consensus has emerged on
      the overall procyclical nature of mortality: perhaps counter-intuitively,
      mortality typically rises above its trend during expansions. This consensus has
      been tarnished by inconsistent reports on the specific age groups and mortality
      causes involved. We show that these inconsistencies result, in part, from the
      trend specifications used in previous panel models. Standard econometric panel
      analysis involves fitting regression models using ordinary least squares,
      employing standard errors which are robust to temporal autocorrelation. The model
      specifications include a fixed effect, and possibly a linear trend, for each time
      series in the panel. We propose alternative methodology based on nonlinear
      detrending. Applying our methodology on data for the 50 US states from 1980 to
      2006, we obtain more precise and consistent results than previous studies. We
      find procyclical mortality in all age groups. We find clear procyclical mortality
      due to respiratory disease and traffic injuries. Predominantly procyclical
      cardiovascular disease mortality and countercyclical suicide are subject to
      substantial state-to-state variation. Neither cancer nor homicide have
      significant macroeconomic association.

PMID- 24587844
TI  - EVALUATING COSTS WITH UNMEASURED CONFOUNDING: A SENSITIVITY ANALYSIS FOR THE
      TREATMENT EFFECT.
AB  - Estimates of the effects of treatment on cost from observational studies are
      subject to bias if there are unmeasured confounders. It is therefore advisable in
      practice to assess the potential magnitude of such biases. We derive a general
      adjustment formula for loglinear models of mean cost and explore special cases
      under plausible assumptions about the distribution of the unmeasured confounder.
      We assess the performance of the adjustment by simulation, in particular,
      examining robustness to a key assumption of conditional independence between the
      unmeasured and measured covariates given the treatment indicator. We apply our
      method to SEER-Medicare cost data for a stage II/III muscle-invasive bladder
      cancer cohort. We evaluate the costs for radical cystectomy vs. combined
      radiation/chemotherapy, and find that the significance of the treatment effect is
      sensitive to plausible unmeasured Bernoulli, Poisson and Gamma confounders.

PMID- 24587845
TI  - FLEXIBLE COVARIATE-ADJUSTED EXACT TESTS OF RANDOMIZED TREATMENT EFFECTS WITH
      APPLICATION TO A TRIAL OF HIV EDUCATION.
AB  - The primary goal of randomized trials is to compare the effects of different
      interventions on some outcome of interest. In addition to the treatment
      assignment and outcome, data on baseline covariates, such as demographic
      characteristics or biomarker measurements, are typically collected. Incorporating
      such auxiliary co-variates in the analysis of randomized trials can increase
      power, but questions remain about how to preserve type I error when incorporating
      such covariates in a flexible way, particularly when the number of randomized
      units is small. Using the Young Citizens study, a cluster randomized trial of an
      educational intervention to promote HIV awareness, we compare several methods to
      evaluate intervention effects when baseline covariates are incorporated
      adaptively. To ascertain the validity of the methods shown in small samples,
      extensive simulation studies were conducted. We demonstrate that randomization
      inference preserves type I error under model selection while tests based on
      asymptotic theory may yield invalid results. We also demonstrate that covariate
      adjustment generally increases power, except at extremely small sample sizes
      using liberal selection procedures. Although shown within the context of HIV
      prevention research, our conclusions have important implications for maximizing
      efficiency and robustness in randomized trials with small samples across
      disciplines.

PMID- 24587846
TI  - MULTI-WAY BLOCKMODELS FOR ANALYZING COORDINATED HIGH-DIMENSIONAL RESPONSES.
AB  - We consider the problem of quantifying temporal coordination between multiple
      high-dimensional responses. We introduce a family of multi-way stochastic
      blockmodels suited for this problem, which avoids pre-processing steps such as
      binning and thresholding commonly adopted for this type of problems, in biology.
      We develop two inference procedures based on collapsed Gibbs sampling and
      variational methods. We provide a thorough evaluation of the proposed methods on
      simulated data, in terms of membership and blockmodel estimation, predictions out
      of-sample, and run-time. We also quantify the effects of censoring procedures
      such as binning and thresholding on the estimation tasks. We use these models to
      carry out an empirical analysis of the functional mechanisms driving the
      coordination between gene expression and metabolite concentrations during carbon
      and nitrogen starvation, in S. cerevisiae.

PMID- 24587847
TI  - Immune and inflammatory pathways in NASH.
AB  - Immune and inflammatory pathways have a central role in the pathogenesis of non
      alcoholic fatty liver disease (NAFLD). Both the innate and adaptive immune
      systems contribute to the development of NAFLD. Pathogen-associated molecular
      patterns and danger-associated molecular patterns are known to activate a variety
      of pattern-recognition receptors that result in inflammation. The key features of
      the immune system and inflammatory pathways in the development of NAFLD are
      discussed in this review. 

PMID- 24587848
TI  - Insulin resistance, steatosis and hepatitis C virus.
AB  - Epidemiological studies have shown an increased occurrence of metabolic disorders
      such as insulin resistance (IR) and steatosis in patients with hepatitis C virus
      (HCV) infection. IR is believed to represent one of the central clinical features
      of the "metabolic syndrome" and the major pathogenetic factor for type 2 diabetes
      mellitus. In patients with chronic HCV hepatitis, IR may have several dangerous
      consequences such as accelerated progression of liver fibrosis, resistance to
      antiviral therapy and development of hepatocellular carcinoma. According to
      recent evidence, the global epidemic of metabolic disorders related to incorrect
      diets will lead physicians to deal with 1.2 billion patients with diabetes in the
      world in 2025. Given the high prevalence of HCV infection in several countries,
      metabolic manifestations will contribute to increasing morbidity and mortality in
      patients with HCV chronic infection in the near future. HCV treatment, shown able
      to decrease both the occurrence of HCV-related IR and diabetes, may reduce the
      risk of the associated morbidities. 

PMID- 24587850
TI  - Comparison and overview of currently available neurotoxins.
AB  - BACKGROUND: Botulinum toxin has been in use since the 1970s. Over the last few
      years, the indications for botulinum toxin use have extended for cosmetic and
      noncosmetic applications. Three preparations of botulinum toxin type A and one
      preparation of botulinum toxin type B are commercially available and approved for
      use in the United States by the United States Food and Drug Administration.
      OBJECTIVE: To review the most recent literature on all commercially available
      botulinum toxins in the United States, their indications, Food and Drug
      Administration approvals, and handling (reconstitution, storage, and dilution).
      METHODS: A literature review (not Cochrane type analysis) using several databases
      (PubMed, MEDLINE, textbooks, Food and Drug Administration homepage, and
      manufacturer information) was performed. CONCLUSION: Several different
      preparations of botulinum toxins exist worldwide, none of which are identical or
      interchangeable. Manufacturer recommendations on all available botulinum
      neurotoxins advise the use of unpreserved saline for reconstitution. Side effects
      are mostly mild and always self-limited. More serious complications are
      associated with higher doses, improper injection techniques, and occur in
      patients with underlying comorbidities.

PMID- 24587849
TI  - Parallel and convergent processing in grid cell, head-direction cell, boundary
      cell, and place cell networks.
AB  - The brain is able to construct internal representations that correspond to
      external spatial coordinates. Such brain maps of the external spatial topography
      may support a number of cognitive functions, including navigation and memory. The
      neuronal building block of brain maps are place cells, which are found throughout
      the hippocampus of rodents and, in a lower proportion, primates. Place cells
      typically fire in one or few restricted areas of space, and each area where a
      cell fires can range, along the dorsoventral axis of the hippocampus, from 30 cm
      to at least several meters. The sensory processing streams that give rise to
      hippocampal place cells are not fully understood, but substantial progress has
      been made in characterizing the entorhinal cortex, which is the gateway between
      neocortical areas and the hippocampus. Entorhinal neurons have diverse spatial
      firing characteristics, and the different entorhinal cell types converge in the
      hippocampus to give rise to a single, spatially modulated cell type-the place
      cell. We therefore suggest that parallel information processing in different
      classes of cells-as is typically observed at lower levels of sensory processing
      continues up into higher level association cortices, including those that provide
      the inputs to hippocampus. WIREs Cogn Sci 2014, 5:207-219. doi: 10.1002/wcs.1272
      Conflict of interest: The authors have declared no conflicts of interest for this
      article. For further resources related to this article, please visit the WIREs
      website.

PMID- 24587851
TI  - Adult bile acid amino transferase deficiency.
AB  - PATIENT: Female, 70 FINAL DIAGNOSIS: Bile acid amino transferase deficiency
      Symptoms: Headache * indigestion * itching skin * nausea * vomiting MEDICATION: -
      Clinical Procedure: - Specialty: Gastroenterology and Hepatology. OBJECTIVE:
      Challenging differential diagnosis. BACKGROUND: Bile acid synthesis impairments
      are difficult to diagnose due to non-specific manifestations related to
      progressive failure to absorb essential fatty acids and fat soluble vitamins and
      failure to maintain normal intestinal microbiota. CASE REPORT: A 70-year-old
      female presented with long-standing history of recurrent headaches, indigestion,
      dry, scaly, itching skin, and fluid around knee joints. Quantitative
      Electroencephalography (QEEG) revealed widespread excess theta maximum in the
      temporal regions. A rare pattern of elevated plasma glycine and taurine led to
      suspicion of BAATD. A stool profile employing molecular probes for commensal
      bacteria revealed elevation of Fusobacteria spp. Implementation of bile acid
      replacement therapy (BART) produced rapid remission of headache and other
      symptoms and a three-month follow up stool profile revealed normalization of
      fecal Fusobacteria populations that remained normal after one year of BART. QEEG
      analyses 4 weeks following BART showed evidence of significant improvement in CNS
      functioning. CONCLUSIONS: This case illustrates the potential for diagnosis of
      latent, adult BAATD by finding a unique pattern of plasma amino acids and
      monitoring of therapy by observing normalization of fecal commensal bacteria and
      functional brain assessments.

PMID- 24587852
TI  - A rare symptom in posttraumatic stress disorder: Spontaneous ejaculation.
AB  - PATIENT: Male, 25 FINAL DIAGNOSIS: Post Traumatic Stress Disorder Symptoms:
      Insomnia * nightmares * spontaneous ejaculation MEDICATION: Paroxentine Clinical
      Procedure: - Specialty: Psychiatry. OBJECTIVE: Unusual clinical course.
      BACKGROUND: Sexual dysfunction is reported to occur more frequently in
      posttraumatic stress disorder (PTSD) patients than in the general population.
      Herein, we present the case of a patient with spontaneous ejaculation that
      developed when severity of PTSD symptoms increased. CASE REPORT: Our patient was
      a 25-year-old single man admitted to a psychiatric polyclinic because of PTSD
      symptoms and concurrent spontaneous ejaculations. He was diagnosed with PTSD
      after clinical interviews. Organic pathology to explain spontaneous ejaculations
      was not detected. Paroxetine treatment was initiated and PTSD symptoms and
      frequency of spontaneous ejaculations were decreased at the clinical follow-up.
      CONCLUSIONS: Assessment of the presented case in the light of the literature
      indicates that his re-experiencing (flashbacks, nightmare) and hyperarousal
      (symptoms of anxiety specific to PTSD) led to an increase in adrenergic system
      activation and, consequently, spontaneous ejaculation without sexual stimulus.
      The effect of Paroxetine in decreasing the frequency of spontaneous erection and
      ejaculation in the presented case is thought to have occurred via control of PTSD
      symptoms and their adverse effects on ejaculation. Treatment based on a
      consideration of PTSD symptoms and autonomic instability might increase the
      positive outcome rate in such patients.

PMID- 24587853
TI  - Mucormycosis in an HIV-infected renal transplant patient: A case report and
      review of the literature.
AB  - PATIENT: Female, 15 FINAL DIAGNOSIS: Mucormycosis Symptoms: Lower extremity
      swelling * respiratory failure * short of breath MEDICATION: - Clinical
      Procedure: - Specialty: Infectious Diseases. OBJECTIVE: Rare disease. BACKGROUND:
      Mucormycosis is an uncommonly encountered clinical syndrome in Human
      Immunodeficiency Virus (HIV)-infected patients. The syndrome is well described in
      solid organ transplant (SOT) patients, in whom it mainly causes pulmonary or
      rhinocerebral disease. Mucormycosis in HIV-infected patients who underwent SOT
      has rarely been described. CASE REPORT: In this article, we describe an HIV
      infected patient with a renal transplant who developed mucormycosis, and we
      review the literature. A 45-year-old African-American female with a history of
      HIV controlled by anti-retrovirals was admitted with shortness of breath, lower
      extremity swelling, and respiratory failure. Bronchoscopic results confirmed
      Mucor on pathology. She was treated with posaconazole and caspofungin, but her
      condition deteriorated. Computed axial tomography (CT) scan of the head without
      contrast showed multiple low attenuation lesions throughout the brain parenchyma,
      with the largest lesion centered in the left basal ganglia with extensive mass
      effect with subfalcine herniation and early transtentorial herniation with acute
      hydrocephalus. Even though we did not have brain tissue to make a precise
      diagnosis, it is likely that the central nervous system involvement in this
      patient was due to mucormycosis. CONCLUSIONS: In summary, we describe the case of
      an HIV-infected patient with renal transplant who died of disseminated
      mucormycosis. As the number of renal transplants in the HIV-infected population
      is increasing, clinicians should be aware of the possibility of disseminated
      mucormycosis. Early diagnosis and effective prophylaxis may alter the course of
      this devastating syndrome.

PMID- 24587854
TI  - Neurofibromatosis induced hip arthritis. An unusual presentation.
AB  - PATIENT: Male, 43 FINAL DIAGNOSIS: Neurofibromatosis Symptoms: Hip pain
      Medication: - Clinical Procedure: - Specialty: Orthopedics and Traumatology.
      OBJECTIVE: Rare disease. BACKGROUND: Neurofibromatosis type 1 is a disease known
      for orthopedic manifestations such as spine deformities, congenital
      pseudarthrosis of the tibia and other bony dysplasias; joint dislocations are
      rare. Joint arthritis caused by neurofibromatosis, with a stable hip, has never
      been reported in the English literature before. CASE REPORT: A 43-year-old man
      diagnosed with neurofibromatosis type 1 (NF-1) presented with hip pain of 5 years
      duration, with no history of trauma and no clinical or radiological signs of
      dislocation. He had classical clinical and radiological signs of hip arthritis,
      with acetabular erosions and femoral head arthritis. The patient was treated with
      total hip arthroplasty metal-on-metal (MoM). CONCLUSIONS: Hip arthritis alone
      without subluxation or dislocation due to NF-1 is an extremely rare presentation.
      This is the first reported presentation and provisional treatment with total hip
      arthroplasty.

PMID- 24587855
TI  - Myopericarditis as a complication of nonspecific colitis.
AB  - PATIENT: Male, 31 FINAL DIAGNOSIS: Myopericarditis Symptoms: Abdominal pain *
      diarrhea MEDICATION: - Clinical Procedure: - Specialty: Cardiology. OBJECTIVE:
      Unusual setting of medical care. BACKGROUND: Myopericarditis is a condition
      involving inflammation of the pericardium and myocardium. It has been reported in
      conjunction with inflammatory bowel disease as well as infectious colitis caused
      by a cardiotropic organism. The etiology of myopericarditis includes a long list
      of infectious causes (especially viral), toxic causes, autoimmune disorders, and
      vasculitides. CASE REPORT: A 31-year-old previously healthy Hispanic man
      complained of sudden onset of watery, non-bloody diarrhea associated with mucus
      and crampy abdominal pain. ECG showed ST-segment elevation in the infero-lateral
      leads, with elevated troponin I level. Urgent cardiac catheterization revealed
      normal coronary arteries and the patient was diagnosed with myopericarditis. The
      echocardiogram results were within normal limits, with 65% ejection fraction and
      no evidence of wall motion abnormalities. Colonoscopy showed macroscopically
      congested mucosa in the descending colon, sigmoid colon, and rectum, with
      scattered petechiae indicative of nonspecific colitis. Microscopic examination of
      obtained biopsies revealed evidence of acute mucosal inflammation without
      ulceration, granulomas or ischemia. The patient was started on Naproxen 250 mg
      twice daily and chest pain started to improve gradually. The patient was
      discharged on Naproxen and was followed up in clinic 2 weeks after discharge,
      where he was found to be completely asymptomatic, with troponin level <0.015
      ng/ml. CONCLUSIONS: Myopericarditis is a challenging diagnosis that has been
      reported in association with colitis, either as an extraintestinal manifestation
      of IBD or due to infectious colitis with a cardiotropic organism.

PMID- 24587856
TI  - Long-term complete remission of metastatic breast cancer, induced by a steroidal
      aromatase inhibitor after failure of a non-steroidal aromatase inhibitor.
AB  - PATIENT: Female, 56 FINAL DIAGNOSIS: Breast cancer Symptoms: Solid mass in the
      right breast Medication: Exemestane Clinical Procedure: - Specialty: Oncology.
      OBJECTIVE: Unusual clinical course. BACKGROUND: The efficacy of third-generation
      aromatase inhibitors for hormone receptor-positive postmenopausal metastatic
      breast cancer is well established. Although several clinical trials have reported
      incomplete cross-resistance between different aromatase inhibitors, few cases of
      complete responses of recurrent metastatic breast cancer occurring after
      substituting a second aromatase inhibitor have been reported. We here present a
      rare case of non-steroidal aromatase inhibitor-tolerant metastatic breast cancer
      with long-term complete remission following substitution of a steroidal aromatase
      inhibitor. CASE REPORT: We present the case of a 56-year-old Japanese woman who
      underwent right breast-conserving surgery for breast cancer, TNM staging T1, N0,
      M0, Stage I. She received adjuvant chemotherapy with 6 cycles of FEC100 and
      radiation therapy, and then began hormonal therapy with anastrozole. Twelve
      months postoperatively, computed tomography (CT) revealed multiple lung
      metastases. Exemestane was substituted for anastrozole. After 3 months of
      exemestane, CT showed that all lung metastases had completely resolved. Her
      complete response was maintained for 5 years: she died during a tsunami 6 years
      after the initial surgery. CONCLUSIONS: Substitution of a steroidal for a non
      steroidal aromatase inhibitor produced a sustained complete remission in a
      patient with hormonal receptor-positive postmenopausal recurrent breast cancer.
      Achieving complete response after switching from a non-steroidal to a steroidal
      aromatase inhibitor in a hormonal receptor-positive postmenopausal recurrent
      breast cancer contributed to a higher quality of life for the patient. Further
      investigation is needed to identify the predictors of long-term remission
      following such a switch.

PMID- 24587857
TI  - Childhood challenges.

PMID- 24587858
TI  - The hip bone is connected to the thigh bone!

PMID- 24587860
TI  - Effect of active versus passive recovery on performance during intrameet swimming
      competition.
AB  - BACKGROUND: During competition, high-performance swimmers are subject to repeated
      physical demands that affect their final performance. Measurement of lactate
      concentration in blood seeks to indirectly gauge physiologic responses to the
      increase in physical exercise. Swimmers face multiple maximal-exertion events
      during competition. Strenuous physical exercise leads to fatigue and, thus, a
      decrease in sports performance. HYPOTHESIS: Regeneration exercises in swimming
      increase the clearance of blood lactate and therefore improve athletic
      performance within a single day of competition. STUDY DESIGN: Crossover study.
      LEVEL OF EVIDENCE: Level 1. METHODS: Of 25 swimmers, 21 were included, with a
      mean age of 17 years. They performed exercises that increased blood lactate on 2
      days. The protocol was a warm-up, followed by a 100-m freestyle workout at full
      speed. Swimming exercises followed that were increasingly demanding, during which
      serial lactatemia measurements were taken. On the first day, regeneration
      exercises were performed; on the second day, the swimmers rested. Next,
      lactatemia was measured, and a timed 100-m freestyle workout was performed at
      maximum speed. RESULTS: The stress exercises increased the mean lactate
      concentration by 4.6 mmol/L, which corresponds to 78% of the initial basal level.
      The postregeneration lactatemia level was lower than that after resting (mean,
      2.76 vs 6.51 mmol/L). The time to swim 100 m after regeneration was 68.11
      seconds, while that after rest was 69.31 seconds. CONCLUSION: Blood lactate
      levels rose by up to 78% after the intensity of the training sessions was
      progressively increased. Regeneration exercises increased the rate in which blood
      lactate dissipated, in comparison with passive recuperation. The rate of lactate
      dissipation for regeneration exercises was 68%. This factor may have improved the
      physical performance of swimmers. CLINICAL RELEVANCE: Regeneration exercises
      improved the performance of swimmers in maximal-exertion competition in a single
      day. The blood lactate level correlated with physical exercise load.

PMID- 24587859
TI  - The recognition and evaluation of patterns of compensatory injury in patients
      with mechanical hip pain.
AB  - CONTEXT: In active individuals with femoroacetabular impingement (FAI), the
      resultant reduction in functional range of motion leads to high impaction loads
      at terminal ranges. These increased forces result in compensatory effects on bony
      and soft tissue structures within the hip joint and hemipelvis. An algorithm is
      useful in evaluating athletes with pre-arthritic, mechanical hip pain and
      associated compensatory disorders. EVIDENCE ACQUISITION: A literature search was
      performed by a review of PubMed articles published from 1976 to 2013. LEVEL OF
      EVIDENCE: Level 4. RESULTS: Increased stresses across the bony hemipelvis result
      when athletes with FAI attempt to achieve supraphysiologic, terminal ranges of
      motion (ROM) through the hip joint required for athletic competition. This can
      manifest as pain within the pubic joint (osteitis pubis), sacroiliac joint, and
      lumbosacral spine. Subclinical posterior hip instability may result when attempts
      to increase hip flexion and internal rotation are not compensated for by
      increased motion through the hemipelvis. Prominence of the anterior inferior
      iliac spine (AIIS) at the level of the acetabular rim can result in impingement
      of the anterior hip joint capsule or iliocapsularis muscle origin against the
      femoral head-neck junction, resulting in a distinct form of mechanical hip
      impingement (AIIS subspine impingement). Iliopsoas impingement (IPI) has also
      been described as an etiology for anterior hip pain. IPI results in a typical 3
      o'clock labral tear as well as an inflamed capsule in close proximity to the
      overlying iliopsoas tendon. Injury in athletic pubalgia occurs during high-energy
      twisting activities in which abnormal hip ROM and resultant pelvic motion lead to
      shearing across the pubic symphysis. CONCLUSION: Failure to recognize and address
      concomitant compensatory injury patterns associated with intra-articular hip
      pathology can result in significant disability and persistent symptoms in
      athletes with pre-arthritic, mechanical hip pain. STRENGTH-OF-RECOMMENDATION
      TAXONOMY SORT: B.

PMID- 24587861
TI  - The running athlete: stress fractures, osteitis pubis, and snapping hips.
AB  - CONTEXT: Pelvic stress fractures, osteitis pubis, and snapping hip syndrome
      account for a portion of the overuse injuries that can occur in the running
      athlete. EVIDENCE ACQUISITION: PUBMED SEARCHES WERE PERFORMED FOR EACH ENTITY
      USING THE FOLLOWING KEYWORDS: snapping hip syndrome, coxa sultans, pelvic stress
      fracture, and osteitis pubis from 2008 to 2013. Topic reviews, case reports, case
      series, and randomized trials were included for review. STUDY DESIGN: Clinical
      review. LEVEL OF EVIDENCE: Level 4. RESULTS: Collectively, 188 articles were
      identified. Of these, 58 were included in this review. CONCLUSION: Based on the
      available evidence, the majority of these overuse injuries can be managed non
      operatively. Primary treatment should include removal from offending activity,
      normalizing regional muscle strength/length imbalances and nutritional
      deficiencies, and mitigating training errors through proper education of the
      athlete and training staff. STRENGTH OF RECOMMENDATION TAXONOMY: C.

PMID- 24587862
TI  - Changes in drop-jump landing biomechanics during prolonged intermittent exercise.
AB  - BACKGROUND: As injury rates rise in the later stages of sporting activities, a
      better understanding of lower extremity biomechanics in the later phases of
      gamelike situations may improve training and injury prevention programs.
      HYPOTHESIS: Lower extremity biomechanics of a drop-jump task (extracted from a
      principal components analysis) would reveal factors associated with risk of
      anterior cruciate ligament injury during a 90-minute individualized intermittent
      exercise protocol (IEP) and for 1 hour following the IEP. STUDY DESIGN:
      Controlled laboratory study. LEVEL OF EVIDENCE: Level 4. METHODS: Fifty-nine
      athletes (29 women, 30 men) completed 3 sessions. The first session assessed
      fitness for an IEP designed to simulate the demands of a soccer match. An
      experimental session assessed drop-jump biomechanics, after a dynamic warm-up,
      every 15 minutes during the 90-minute IEP, and for 1 hour following the IEP. A
      control session with no exercise assessed drop-jump performance at the same
      intervals. RESULTS: Two biomechanical factors early in the first half (hip
      flexion at initial contact and hip loading; ankle loading and knee shear force)
      decreased at the end of the IEP and into the 60-minute recovery period, while a
      third factor (knee loading) decreased only during the recovery period (P <=
      0.05). CONCLUSION: The individualized sport-specific IEP may have more subtle
      effects on landing biomechanics when compared with short-term, exhaustive fatigue
      protocols. CLINICAL RELEVANCE: Potentially injurious landing biomechanics may not
      occur until the later stages of soccer activity.

PMID- 24587863
TI  - Concussion history and knowledge base in competitive equestrian athletes.
AB  - BACKGROUND: Head injuries are responsible for the majority of serious equestrian
      sports injuries and deaths. Because of significant health risks to equestrians,
      education regarding the prevention of head and brain injuries is essential.
      HYPOTHESIS: A significant number of riders have experienced a concussion, and few
      have knowledge of concussion. STUDY DESIGN: Cross-sectional study. LEVEL OF
      EVIDENCE: Level 2. METHODS: Ninety-four riders competing, riding, or attending
      equestrian events at the Palm Beach International Equestrian Center in
      Wellington, Florida, from January to April 2010 were surveyed. Measures of
      central tendency were utilized to evaluate response patterns. RESULTS: Almost
      half of equestrian riders (44%) experienced concussions during their careers.
      Those riders who suffered a brain injury were likely to return to riding without
      seeking medical clearance. Almost 40% of riders were never educated regarding
      concussions, while 15% received education from their trainers. CONCLUSION:
      Education of riders, parents, and horse trainers is needed to raise awareness of
      concussions and reduce the likelihood of subsequent injuries.

PMID- 24587864
TI  - Sports hernia/athletic pubalgia: evaluation and management.
AB  - CONTEXT: Sports hernia/athletic pubalgia has received increasing attention as a
      source of disability and time lost from athletics. Studies are limited, however,
      lacking consistent objective criteria for making the diagnosis and assessing
      outcomes. EVIDENCE ACQUISITION: PubMed database through January 2013 and hand
      searches of the reference lists of pertinent articles. STUDY DESIGN: Review
      article. LEVEL OF EVIDENCE: Level 5. RESULTS: Nonsurgical outcomes have not been
      well reported. Various surgical approaches have return-to-athletic activity rates
      of >80% regardless of the approach. The variety of procedures and lack of
      outcomes measures in these studies make it difficult to compare one surgical
      approach to another. There is increasing evidence that there is an association
      between range of motion-limiting hip disorders (femoroacetabular impingement) and
      sports hernia/athletic pubalgia in a subset of athletes. This has added increased
      complexity to the decision-making process regarding treatment. CONCLUSION: An
      association between femoroacetabular impingement and athletic pubalgia has been
      recognized, with better outcomes reported when both are managed concurrently or
      in a staged manner.

PMID- 24587865
TI  - Case report: pelvic congestion syndrome as an unusual etiology for chronic hip
      pain in 2 active, middle-age women.
AB  - CONTEXT: The past 2 decades have shown a dramatic increase in the number of
      pelvic and hip injuries in female athletes. Accurate diagnosis of hip pain in
      active women has proven to be a challenge, as there is an extensive differential
      including both musculoskeletal and visceral problems. While the incidence of
      pelvic congestion syndrome (PCS) is not known, this condition may manifest as
      chronic hip pain in this patient population. EVIDENCE ACQUISITION: A PubMed
      search was undertaken for articles published in English from 1980 to 2012.
      Additional references were accrued from reference lists of research articles.
      STUDY DESIGN: Case series. LEVEL OF EVIDENCE: Level 3. RESULTS: Diagnosis was
      established using magnetic resonance imaging. Both women were evaluated and
      treated by interventional radiology with gonadal vein embolization. Initial
      evaluation and subsequent follow-up was completed in the Sports Medicine Clinic
      to monitor chronic hip pain symptoms. Both patients experienced significant
      alleviation of chronic hip pain symptoms within several months after gonadal vein
      embolization, allowing for a return to the previous level of activity.
      CONCLUSION: Although PCS most commonly presents as pelvic pain, it is important
      to consider this condition in athletes with persistent hip pain. PCS may also
      present with the primary symptom of hip pain as in the 2 case reports described.
      With more awareness of this condition and appropriate diagnosis, PCS as an
      unusual etiology of chronic hip pain may be effectively treated with gonadal vein
      embolization.

PMID- 24587866
TI  - Attention deficit hyperactivity disorder and athletes.
AB  - CONTEXT: Attention deficit hyperactivity disorder (ADHD) is common in the general
      population, and many individuals with this condition participate in sports
      activity at all competition levels. EVIDENCE ACQUISITION: Related studies were
      selected through literature searches of PubMed, MEDLINE, and Cochrane databases
      for the years 1991 to 2011. Key search terms were ADD, ADHD, sports, athletes,
      athletics, guidelines, NCAA, WADA, IOC, college, concussion, diagnosis,
      management, treatment, evaluation, return-to-play, pharmacotherapy, adult,
      adolescent, student, screening, injury, risk, neuropsychiatry, TBI, traumatic
      brain injury, and epidemiology. STUDY DESIGN: Literature review. LEVEL OF
      EVIDENCE: Level 4. RESULTS: ADHD usually has an early onset, with delayed
      diagnosis in some patients due to heterogeneous presentations. Suspected cases
      can be evaluated with available diagnostic tools and confirmed clinically.
      Athletes with ADHD may participate at all competition levels. CONCLUSION:
      Athletes with ADHD are able to participate at all competition levels by following
      published guidelines and requirements. Exercise benefits many athletes with ADHD.
      The relationship between ADHD and concussion syndromes is currently under
      investigation.

PMID- 24587867
TI  - The etiology of femoroacetabular impingement: what we know and what we don't.
AB  - CONTEXT: Several risk factors may cause femoroacetabular impingement (FAI).
      Knowledge of causation would identify patients for early intervention, prior to
      the development of painful intra-articular damage. DATA SOURCES: PubMed, MEDLINE,
      EMBASE, and related article reference lists were screened for relevant studies
      published between January 2000 and December 2013. STUDY SELECTION: Inclusion
      criteria were (1) etiology of FAI, (2) original FAI clinical data, and (3)
      English language. Case reports of fewer than 3 patients were excluded. STUDY
      DESIGN: Systematic review. LEVEL OF EVIDENCE: Level 4. RESULTS: In all, 754
      studies were screened, with 18 meeting the eligibility criteria. There were 13
      comparative observational studies and 5 case series. The studies pertained to
      intrinsic patient factors (n = 2), activity/developmental factors (n = 8), hip
      disease (n = 5), postsurgical changes (n = 2), and malunion after hip fracture (n
      = 1). CONCLUSION: A combination of intrinsic patient and developmental factors,
      activities involving repetitive hip motion, pediatric hip disease, and hip
      related surgical procedures may contribute to the development of FAI.

PMID- 24587868
TI  - What's New in Femoroacetabular Impingement Surgery: Will We Be Better in 2023?
AB  - CONTEXT: Femoroacetabular impingement (FAI) has been described as a common cause
      of hip pain in young adults. This leads to abnormal hip joint mechanics and
      contact pressures. The associated pathomechanics can lead to the development of
      early osteoarthritis. Better understanding of the anatomy and pathophysiology,
      biomechanics, and diagnostic and therapeutic advances has led to improved
      clinical outcomes. A growing body of evidence has set the foundation for future
      progress in the treatment of this commonly encountered condition. EVIDENCE
      ACQUISITION: The PubMed database was searched for English-language articles
      pertaining to FAI over the past 15 years (1998-2013). STUDY DESIGN: Retrospective
      literature review. LEVEL OF EVIDENCE: Level 4. RESULTS: The authors evaluated and
      discussed the current evidence regarding the anatomy, physiology, biomechanics,
      imaging, and clinical outcomes of surgical intervention for FAI. Based on this
      information, future directions for improving the diagnosis and management of FAI
      are proposed. CONCLUSION: There remains a diverse approach to the diagnosis and
      management of cam- and/or pincer-type FAI. Recent advances in clinical diagnosis,
      imaging, indications, and arthroscopic techniques have led to improved outcomes
      and have set the foundation for future progress in the management of this
      condition. STRENGTH OF RECOMMENDATION TAXONOMY SORT: B.

PMID- 24587869
TI  - Radiographic evidence of femoroacetabular impingement in athletes with athletic
      pubalgia.
AB  - BACKGROUND: Two of the most common causes of groin pain in athletes are
      femoroacetabular impingement (FAI) and athletic pubalgia. An association between
      the 2 is apparent, but the prevalence of radiographic signs of FAI in patients
      undergoing athletic pubalgia surgery remains unknown. The purpose of this study
      was to determine the prevalence of radiologic signs of FAI in patients with
      athletic pubalgia. HYPOTHESIS: We hypothesized that patients with athletic
      pubalgia would have a high prevalence of underlying FAI. STUDY DESIGN: Case
      series. LEVEL OF EVIDENCE: Level 4. METHODS: A retrospective review of all
      patients evaluated at our institution with athletic pubalgia who underwent
      surgical treatment (ie, for sports hernia) from 1999 to 2011 was performed. The
      radiographs of patients with athletic pubalgia were reviewed for radiographic
      signs of FAI. Alpha angles were measured using frog-leg lateral radiographs.
      Pincer lesions were identified by measuring the lateral center-edge angle and
      identifying the presence of a "crossover" sign on anteroposterior radiographs.
      Phone follow-up was performed 2 years or more after the initial sports hernia
      surgery to evaluate recurrent symptoms. RESULTS: Forty-three patients underwent
      56 athletic pubalgia surgeries. Radiographic evidence of FAI was identified in at
      least 1 hip in 37 of 43 patients (86%). Cam lesions were identified in 83.7% of
      the population; the alpha angle averaged 66.7 degrees  +/- 17.9 degrees  for all
      hips. Pincer lesions were present in 28% of the hips. Eight patients had
      recurrent groin pain, 3 patients had revision athletic pubalgia surgery, and 1
      had hip arthroscopy. CONCLUSION: The study demonstrates a high prevalence of
      radiographic FAI in patients with athletic pubalgia. CLINICAL RELEVANCE:
      Underlying FAI may be a cause of continued groin pain after athletic pubalgia
      surgery. Patients with athletic pubalgia should be evaluated closely for FAI.

PMID- 24587871
TI  - Modeling the Relationship between Trauma and Psychological Distress among HIV
      Positive and HIV-Negative Women.
AB  - This study investigated the association between cumulative exposure to multiple
      traumatic events and psychological distress, as mediated by problematic substance
      use and impaired psychosocial resources. A sample of HIV-positive and HIV
      negative women were assessed for a history of childhood and adult sexual abuse
      and non-sexual trauma as predictors of psychological distress (i.e., depression,
      non-specific anxiety, and posttraumatic stress), as mediated by problematic
      alcohol and drug use and psychosocial resources (i.e., social support, self
      esteem and optimism). Structural equation modeling confirmed that cumulative
      trauma exposure is positively associated with greater psychological distress, and
      that this association is partially mediated through impaired psychosocial
      resources. However, although cumulative trauma was associated with greater
      problematic substance use, substance use did not mediate the relationship between
      trauma and psychological distress.

PMID- 24587872
TI  - Risk of Ipsilateral and Contralateral Cancer in BRCA Mutation Carriers with
      Breast Cancer.
AB  - BRCA1 and BRCA2 mutation carriers with breast cancer have a high risk of
      ipsilateral breast cancer tumor recurrence (IBTR) and a high lifetime risk of
      contralateral breast cancer (CBC). The IBTR risk is significantly higher in women
      who elect breast conservation. Oophorectomy has a protective effect for both
      ipsilateral breast tumor recurrence and CBC. Patients with younger age of breast
      cancer onset have a significantly greater risk of CBC. Given the higher risk of
      IBTR and CBC, when indicated, patients with breast cancer should undergo genetic
      counseling early in their treatment course to assist them in their surgical
      decision-making. Knowledge of expected outcomes for BRCA1/2 mutation carriers
      following breast cancer treatment can help appropriately council patients and
      personalize cancer therapy.

PMID- 24587873
TI  - Expression profile of fas-fas ligand in spiral ganglion cells during apoptosis.
AB  - OBJECTIVES: To examine the expression profile of Fas-Fas ligand (FasL) during
      glutamate (Glu)-induced spiral ganglion cell (SGC) apoptosis. METHODS: Cultured
      SGCs were treated with 10-mM, 25-mM, and 50-mM concentrations of Glu and
      incubated for 24 or 48 hours. The expression intensity of FasL, Fas, caspase 3,
      and morphology of single SGC were evaluated using immunofluorescence staining.
      RESULTS: In semiquantitative analysis of the Glu-treated SGC, FasL, and caspase 3
      expression intensity were increased with concentration- and time-dependent
      manner. Fas expression intensity did not change with different concentration at
      48 hours. In morphologic analysis of the Glu-treated SGC, number of apoptotic
      cells were increased with concentration- and time-dependent manner. CONCLUSION:
      FasL was expressed in apoptotic SGCs, suggesting that the Fas-FasL signaling
      pathway may be involved in the Glu-induced apoptosis of dissociated SGCs.

PMID- 24587874
TI  - Decreased pattern-recognition receptor-mediated cytokine mRNA expression in obese
      children with otitis media with effusion.
AB  - OBJECTIVES: To assess innate and humoral immune responses in middle ear effusion
      of obese pediatric patients with otitis media with effusion (OME). METHODS: We
      evaluated 219 children with OME, of whom 21 were obese and 198 were non-obese. We
      compared the expression in middle ear effusion of mRNAs encoding toll-like
      receptors (TLR) 2, 4, 5, and 9; nucleotide-binding oligomerization domains (NOD)
      1 and 2; retinoic acid-inducible gene (RIG)-I; interleukins (IL)-6, -10, and -12;
      interferon (IFN)-gamma; and tumor necrosis factor (TNF)-alpha mRNAs. We also
      compared the expression of immunoglobulins IgG, IgA, and IgM and the bacterial
      detection rate in the two groups. RESULTS: TLR2-mediated expression of IL-6 mRNA,
      TLR4-mediated expression of IL-6 and IL-10 mRNA, TLR5-mediated expression of IL
      6, IL-10, and TNF-alpha mRNA, TLR9-mediated expression of IL-6 mRNA, and NOD2
      mediated expression of IL-6, IL-12, and TNF-alpha mRNA were significantly lower
      in obese than in non-obese children (P<0.05). However, concentrations of IgG,
      IgA, and IgM in middle ear effusion were lower in obese than in non-obese
      children, but none of these differences was significant (P>0.05). CONCLUSION:
      Mean body mass index was higher and pattern-recognition receptor-mediated
      cytokine mRNA expression was lower in obese than in non-obese children with OME.

PMID- 24587875
TI  - Protective effect of hexane and ethanol extract of piper longum L. On gentamicin
      induced hair cell loss in neonatal cultures.
AB  - OBJECTIVES: Gentamicin (GM) is a commonly used aminoglycoside antibiotic that
      generates free oxygen radicals within the inner ear, which can cause vestibulo
      cochlear toxicity and permanent damage to the sensory hair cells and neurons.
      Piper longum L. (PL) is a well-known spice and traditional medicine in Asia and
      Pacific islands, which has been reported to exhibit a wide spectrum of activity,
      including antioxidant activity. In this study, we evaluated the effect of
      hexane:ethanol (2:8) PL extract (subfraction of PL [SPL] extract) on GM-induced
      hair cell loss in basal, middle and apical regions in a neonatal cochlea
      cultures. METHODS: The protective effects of SPL extract were measured by
      phalloidin staining of cultures from postnatal day 2-3 mice with GM-induced hair
      cell loss. The anti-apoptosis activity of SPL extract was measured using double
      labeling by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)
      and myosin-7a staining. The radical-scavenging activity of SPL extract was
      assessed using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. RESULTS: SPL
      extract at a concentration of 1 ug/mL significantly inhibited GM-induced hair
      cell loss at basal and middle region of cochlea, while 5 ug/mL was effective
      against apical region hair cell loss. The protective effect of SPL extract was
      concentration dependent and hair cells retained their stereocilia in explants
      treated with SPL extract prior to treatment with 0.3 mM GM. SPL extract decreased
      GM-induced apoptosis of hair cells as assessed by TUNEL staining. The outer hair
      and inner hair counts were not decreased in SPL extract treated groups in compare
      to GM treated explants. Additionally, SPL extract showed concentration dependent
      radical scavenging activity in a DPPH assay. CONCLUSION: An anti-apoptosis effect
      and potent radical scavenger activity of SPL extract protects from GM-induced
      hair cell loss at basal, middle and apical regions in neonatal cochlea cultures.

PMID- 24587876
TI  - Olfactory identification test using familiar distracters for koreans.
AB  - OBJECTIVES: Odors used in an odor identification test should be familiar to the
      subject, but there are some unfamiliar distracters in Korean version of Sniffin'
      stick (KVSS) II identification test. In this study, we used the results of the
      original version of KVSS II identification to modify the KVSS II identification
      test. METHODS: Eighty-three participants took an original version of KVSS II
      identification test and a visual analogue scale of subjective odor function. KVSS
      II identification which has 16 items was performed to choose one out of four
      odors items. And visual analogue scale was checked from 0 to 10 points of their
      subjective olfactory function. Two weeks later they took the modified version of
      KVSS II identification test. Hyposmic or anosmic patients were excluded. RESULTS:
      The mean score of the original version of KVSS II identification and modified
      version of KVSS II identification were 11.3 and 12.5, respectively (P<0.05). The
      KVSS II identification test and subjective olfactory function were positively
      correlated (r=0.247, P<0.05), as were the modified KVSS II identification test
      and subjective olfactory function (r=0.329, P<0.05). CONCLUSION: After
      modification of distracters, KVSS II identification test appears to be suited for
      assessment of olfactory function.

PMID- 24587877
TI  - Development of the korean version of the sleep apnea quality of life index.
AB  - OBJECTIVES: Obstructive sleep apnea (OSA) is a disorder characterized by
      repetitive partial or complete occlusion of the upper airway during sleep that
      affects quality of life. The aim of this study was to develop the Korean version
      of the sleep apnea quality of life index (K-SAQLI) and apply it in Korean
      patients with OSA. METHODS: Ninety-three patients with OSA completed the K-SAQLI.
      Its construct validity and responsiveness were tested by comparing the baseline
      and change scores obtained in each domain (i.e., daily functioning, social
      interactions, emotional functioning, and symptoms) using the medical outcome
      survey-short form 36 (SF-36). RESULTS: The Cronbach alpha coefficients of
      internal reliability exceeded 0.60 in all the domains (daily functioning, 0.89;
      social interactions, 0.88; emotional functioning, 0.92; symptoms, 0.67; and
      total, 0.94). The K-SAQLI had a high test-retest correlation coefficient of 0.73
      in the 20 randomized selected patients. The construct validity was confirmed by
      significant correlations with SF-36 subscale scores. CONCLUSION: The results of
      this study demonstrate that the K-SAQLI may be applicable for clinical purposes.

PMID- 24587878
TI  - A Randomized, Multi-Center, Single Blind, Active-Controlled, Matched Pairs
      Clinical Study to Evaluate Prevention of Adhesion Formation and Safety of HyFence
      in Patients After Endoscopic Sinus Surgery.
AB  - OBJECTIVES: Recurrent mucosal disease and anatomic obstruction are commonly cited
      causes of failed endoscopic sinus surgery (ESS). Hyaluronic acid (HA) has been
      reported to reduce scarring and to promote wound healing in sinonasal surgery.
      HyFence is HA stabilized by 1, 4-butandiol diglycidyl ether, which makes it less
      water-soluble and highly viscoelastic. The purpose of this study is to examine
      the anti-adhesion effect of HyFence after ESS compared to that of HA-CMC (Guardix
      Sol). METHODS: Seventy-four patients with chronic rhinosinusitis who underwent
      ESS were included in the study. After the ESS procedure, Merocel was placed in
      the ethmoidectomized areas of the both sides. Five milliliters of Guardix-Sol was
      then applied to the Merocel of one side and HyFence LV was applied to the other
      side. The effect of the agents was evaluated at one, two, and four weeks after
      surgery by endoscopic examination. The severity of adhesion, edema, infection and
      complications were evaluated. RESULTS: There was no significant difference in the
      incidence of postoperative adhesion between the HyFence group and the Guardix-Sol
      group (P>0.05). Mean postoperative grades of edema and infection showed no
      significant difference between groups (P>0.05). There was no significant
      postoperative complications associated with either anti-adhesion agent (P>0.05).
      CONCLUSION: HyFence has equivalent anti-adhesion effect compared to Guardix-Sol
      following ESS.

PMID- 24587879
TI  - Risk factors and survival outcomes for patients with anastomotic leakage after
      surgery for head and neck squamous cell carcinoma.
AB  - OBJECTIVES: This study evaluated the risk factors for anastomotic leakage (AL)
      and survival outcomes in patients with head and neck squamous cell carcinoma
      (HNSCC). METHODS: Patients with HNSCC who underwent surgery carrying potential AL
      from 2003 through 2009 were included in this study. Univariate and multivariate
      analyses were performed and patient survival was calculated by the Kaplan-Meier
      method. RESULTS: Of 232 eligible patients, 25 (10.8%) developed AL. Univariate
      analyses revealed that primary tumor site, salvage surgery, perineural invasion,
      radiotherapy, chemotherapy, and blood transfusion were significantly associated
      with the occurrence of AL (P<0.05). Independent risk factors for AL were salvage
      surgery and blood transfusion (P<0.01). On univariate analysis, AL was
      significantly associated with overall (OS) and disease-free survivals (DFS;
      P<0.05) but not with decreased locoregional control (LRC) rate (P=0.07). The 5
      year DFS rate was significantly different between the non-leakage and leakage
      groups (70.9% vs. 27.7%, P<0.001). Multivariate analysis showed, however, that AL
      was not an independent variable of LRC, DFS, or OS (P>0.1). CONCLUSION: Patients
      who received salvage surgery and blood transfusion may require careful
      surveillance for development of AL, which has a tendency toward decreased
      survival.

PMID- 24587880
TI  - Association Study of FOS-Like Antigen-2 Promoter Polymorphisms With Papillary
      Thyroid Cancer in Korean Population.
AB  - OBJECTIVES: FOS-like antigen-2 (FOSL-2), a member of the FOS gene family, encode
      leucine zipper proteins that can heterodimerize with proteins of Jun family.
      Thus, activating protein (AP)-1 transcription factor is formed, has a crucial
      role in proliferation, differentiation and apoptosis of normal tissue as well as
      oncogenic transformation and progression. We performed an association study of
      single nucleotide polymorphisms (SNPs) in the FOSL-2 with papillary thyroid
      cancer (PTC). We also estimated the relationships between the SNPs and the
      clinicopathologic characteristics of PTC. METHODS: One promoter SNPs (rs925255)
      of FOSL-2 gene were genotyped with direct sequencing method in 94 PTC and 213
      controls. PTC patients were dichotomized and compared with respect to clinical
      parameters of PTC. Genetic data were analyzed using Helixtree, SNPAnalyzer,
      SNPStats. Multivariate logistic regression analysis was fulfilled to evaluate the
      genetic effect with adjustment for age and sex. RESULTS: SNP (rs925255) in FOSL-2
      showed a significant association (codominant 1 model [G/G vs. A/G]: odds ratio
      [OR], 0.531, 95% confidence interval [CI], 0.293 to 0.96, P=0.036; dominant
      model: OR, 0.50, 95% CI, 0.28 to 0.89, P=0.015) with PTC. The frequency of allele
      G in rs925255 was also significantly associated with PTC (OR, 0.59; 95% CI, 0.34
      to 0.91; P=0.02). But we fail to prove significant association between this
      polymorphism (rs925255) and clinico-pathological parameters. CONCLUSION: Our
      findings suggest that the rs925255 SNP and its allele G show significant
      association with the PTC in Korean population.

PMID- 24587881
TI  - Favorable vocal fold wound healing induced by platelet-rich plasma injection.
AB  - OBJECTIVES: To introduce a new injection material for vocal fold diseases, which
      could be readily translated to clinical practice, we investigated the
      effectiveness of platelet-rich plasma (PRP) injection on the injured vocal fold
      in terms of histological recovery. METHODS: Blood samples were drawn from New
      Zealand White rabbits and PRP was isolated through centrifugation and separation
      of the samples. Using a CO2 laser, we made a linear wound in the 24 vocal fold
      sides of 12 rabbits and injected each wound with PRP on one vocal fold side and
      normal saline (NS) on the other. Morphologic analyses were conducted at 2, 4, and
      12 weeks after injection, and inflammatory response, collagen deposit, and
      changes in growth factors were assessed using H&E and masson trichrome (MT)
      staining and western blot assay. RESULTS: PRP was prepared in approximately 40
      minutes. The mean platelet concentration was 1,315,000 platelets/mm(3). In
      morphological analyses, decreased granulation was observed in the PRP-injected
      vocal folds (P<0.05). However, the irregular surface and atrophic change were not
      difference. Histological findings revealed significant inflammation and collagen
      deposition in NS-injected vocal folds, whereas the PRP-injected vocal folds
      exhibited less (P<0.05). However, the inflammatory reaction and fibrosis were not
      difference. In western blot assay, increased amounts of growth factors were
      observed in PRP-injected vocal folds. CONCLUSION: Injection of injured rabbit
      vocal folds with PRP led to improved wound healing and fewer signs of scarring as
      demonstrated by decreased inflammation and collagen deposition. The increased
      vocal fold regeneration may be due to the growth factors associated with PRP.

PMID- 24587882
TI  - Loss of Heterozygosities in Five Tumor Suppressor Genes (FHIT Gene, p16, pRb, E
      Cadherin and p53) in Thyroid Tumors.
AB  - OBJECTIVES: To evaluate the loss of heterozygosities (LOH) of chromosomes 3p14
      (FHIT gene), 9p21 (p16), 13q21 (pRb), 6q22 (E-cadherin) and 17p13 (p53) in
      various thyroid tumors. METHODS: Eighty thyroid tumor cases (20 follicular
      adenomas, 10 follicular carcinomas, and 50 papillary carcinomas) have been
      analyzed for the presence of LOH in chromosomes 3p14, 9p21, 13q21, 6q22, and
      17p13 allelic loss, using microsatellite markers and DNA obtained from formalin
      fixed paraffin-embedded archival tissues. RESULTS: LOH on 3p14 was found in
      10.5%, 33.3%, and 30.4% of follicular adenomas, follicular carcinomas, and
      papillary carcinomas, respectively. LOH on 9p21 was detected in 6%, 44.4%, and
      47.8%, respectively. LOH on pRb gene was found in 5.3%, 20.0%, and 35.4%,
      respectively. LOH on E-cadherin gene was found in 5.3%, 22.2%, and 43.8%,
      respectively. LOH on 17p13 was detected in 0%, 40%, and 45.8%, respectively. LOH
      in FHIT gene, p16, pRb, E-cadherin, and p53 genes were more frequently identified
      in follicular carcinoma and papillary carcinoma than in follicular adenoma.
      CONCLUSION: LOH results of the five tumor suppressor genes (FHIT gene, p16, pRb,
      E-cadherin, and p53) showed statistical differences between benign tumor and
      malignant tumor. Among papillary carcinoma, LOH in p16, E-cadherin and p53 genes
      well correlated with poorly differentiated grade, and LOH of E-cadherin was
      associated with lymph node metastasis.

PMID- 24587883
TI  - Petrositis With Bilateral Abducens Nerve Palsies complicated by Acute Otitis
      Media.
AB  - Petrous apicitis is a rare but fatal complication of otitis media. An infection
      within the middle ear can extend within the temporal bone into the air cells of
      the petrous apex. With only the thin dura mater separating the trigeminal
      ganglion and the 6th cranial nerve from the bony petrous apex, they are
      vulnerable to inflammatory processes, resulting in deep facial pain, lateral
      rectus muscle paralysis, and diplopia. In 1904, Gradenigo described a triad of
      symptoms related to petrous apicitis, including acute suppurative otitis media,
      deep facial pain resulting from trigeminal involvement, and abducens nerve palsy.
      It has traditionally been treated with surgery, but recent advances in imaging,
      with improved antibiotic treatment, allow conservative management. In this case
      report, we describe a clinical and neuroradiological evolution of a child with a
      petrous apicitis after acute otitis media, which was managed medically with a
      positive outcome. 

PMID- 24587884
TI  - Aggravation of Relapsing Polychondritis due to the Infection and Its
      Manifestation on a Nasal Tip Graft.
AB  - Relapsing polychondritis (RP) is an uncommon systemic disease that is
      characterized by episodic and progressive inflammation of the cartilaginous
      structures, which can be very debilitating and in some instances life
      threatening. The pathogenic pathways of RP are largely unknown. However, several
      hypothesis have been suggested. We had an interesting case of aggravation of RP
      due to the infection. Graft cartilage on the nasal tip was affected by RP also.
      This case can give a clue of revealing the pathogenesis of RP. We introduce a
      case with a review of the literature. 

PMID- 24587885
TI  - Palatal implants for persistent snoring and mild obstructive sleep apnea after
      laser-assisted uvulopalatoplasty.
AB  - Laser-assisted uvulopalatoplasty (LAUP) was widely performed in 1990s as a
      surgical therapeutic procedure to improve snoring or mild obstructive sleep apnea
      (OSA). However, LAUP is not currently recommended as a treatment for OSA because
      the evidence for its efficacy is insufficient. Little is known about alternative
      minimally invasive surgery in patients who refuse continuous positive airway
      pressure or oral appliance after failed LAUP. We present a case of successful
      surgical treatment of persistent snoring and mild OSA with palatal implants after
      LAUP. This case suggests that palatal implants may be offered as an alternative
      surgical procedure for selective patients with persistent or recurrent snoring or
      mild OSA after LAUP. 

PMID- 24587886
TI  - Coexistence of a carotid body tumor and thyroglossal duct carcinoma with cervical
      lymph node metastasis.
AB  - Thyroglossal duct carcinoma is uncommon, occurring in approximately 1% of all
      thyroglossal duct remnants. This rare neoplasm is characterized by relatively
      nonaggressive behavior with infrequent lymph nodal spread. Another rare neoplasm
      of the head and neck region is a carotid body tumor. A 78-year-old woman with a 3
      year history of midline and bilateral neck masses was referred to us. Fine needle
      aspiration biopsies and a computed tomography scan suggested the diagnosis of
      thyroglossal duct carcinoma with cervical lymph node metastasis. Interestingly,
      the left-side neck mass was found to be splaying the carotid bifurcation, on
      computed tomography imaging. Carotid arteriography demonstrated a highly vascular
      mass in the bifurcation of the carotid artery that was compressing the internal
      and external carotid arteries. To our knowledge, this is the first reported
      instance of a thyroglossal duct carcinoma with neck metastasis accompanied by a
      carotid body tumor. In addition, the carotid body tumor in this case mimicked
      neck metastasis from the thyroglossal duct carcinoma. 

PMID- 24587887
TI  - Atypical fibroxanthoma in head and neck.
AB  - Atypical fibroxanthoma is a pleomorphic spindle cell tumor of the dermis and it's
      been known to be a benign lesion clinically in spite of malignant histologic
      features. But recurrence is estimated at between 2%-20% and metastasis has been
      reported. We are about to describe a 70-year-old man with the lesion developed on
      the left infra-auricular area. The lesion was located superficially and is
      composed of compact pleomorphic spindle cells and several bizarre multinucleated
      giant cells. The patient was treated with wide excision. We would like to discuss
      about this case with a review of literatures. 

PMID- 24587888
TI  - A hypopharyngeal ductal cyst masquerading as a laryngopharyngeal reflux disease.
AB  - The ductal cyst of the hypopharynx is a very rare tumor. We report a case of
      hypopharyngeal ductal cyst in a 63-year-old man presenting with globus sensation.
      It was removed by a laryngomicrosurgical technique, using a microdissection
      electrode. Masses of the hypopharynx may not always be easily visible on routine
      examination of the hypopharynx with flexible fiberoptic laryngoscopes.
      Particularly in cases of benign tumors, the diagnosis may be delayed due to a
      prolonged history of mild and subtle symptoms. We missed the hypopharyngeal mass
      at the initial presentation, but could detect the mass in the pyriform sinus with
      a double contrast barium swallow study. We describe the diagnostic method to
      detect hypopharyngeal tumors and the treatment of benign hypopharyngeal masses. 

PMID- 24587890
TI  - Achieving appropriate regulations for electronic cigarettes.
AB  - A growing body of scientific studies show that e-cigarettes may serve as an
      acceptable substitute for smoking tobacco cigarettes, thereby reducing or
      eliminating exposure to harmful elements in smoke. The success of e-cigarettes is
      such that sales of these products are rapidly gaining on traditional cigarettes.
      The rapidly evolving phenomenon is raising concerns for the health community,
      pharmaceutical industry, health regulators and state governments. Obviously,
      these products need to be adequately regulated, primarily to protect users.
      Depending on the form and intended scope, certain regulatory decisions may have
      diverse unintended consequences on public health and may face many different
      challenges. Ideally, before any regulations are enacted, the regulatory body will
      require sufficient scientific research to verify that a problem does exist,
      quantify the problem, explore all potential solutions including making no change
      at all, determine the possible consequences of each, and then select the solution
      that is best for public health. Here we present an overview on the existing and
      deeming regulatory decisions for electronic cigarettes. We challenge them, based
      on the mounting scientific evidence with the ultimate goal of proposing
      appropriate recommendations while minimizing potential unintended consequences of
      ill-informed regulation. 

PMID- 24587891
TI  - First-line natalizumab in multiple sclerosis: rationale, patient selection,
      benefits and risks.
AB  - Natalizumab (NTZ) is a highly effective disease modifying therapy for the
      treatment of relapsing forms of multiple sclerosis (MS). Despite evidence to
      support its use as first-line therapy, risk of NTZ-associated progressive
      multifocal leukoencephalopathy (PML) has largely contributed to it being
      relegated to a second-line position. Recent preliminary data may allow for a more
      accurate analysis of JC virus (JCV) risk stratification of a given patient's PML
      risk. Herein we propose an algorithm to help guide clinicians through this
      decision-making process. We recommend that NTZ be considered for first-line use
      in JCV antibody negative MS patients, JCV 'low positive' MS patients without
      prior exposure to immunosuppression and for a limited period (12-24 months) in
      JCV 'high positive' MS patients with an aggressive disease course . We caution
      against first-line use in JCV antibody 'high positive' patients beyond 12-24
      months and any JCV antibody positive patient with a history of prior
      immunosuppression. 

PMID- 24587892
TI  - Fidaxomicin in Clostridium difficile infection: latest evidence and clinical
      guidance.
AB  - The incidence of Clostridium difficile infection (CDI) has risen 400% in the last
      decade. It currently ranks as the third most common nosocomial infection. CDI has
      now crossed over as a community-acquired infection. The major failing of current
      therapeutic options for the management of CDI is recurrence of disease after the
      completion of treatment. Fidaxomicin has been proven to be superior to vancomycin
      in successful sustained clinical response to therapy. Improved outcomes may be
      due to reduced collateral damage to the gut microflora by fidaxomicin,
      bactericidal activity, inhibition of Clostridial toxin formation and inhibition
      of new sporulation. This superiority is maintained in groups previously reported
      as being at high risk for CDI recurrence including those: with relapsed infection
      after a single treatment course; on concomitant antibiotic therapy; aged >65
      years; with cancer; and with chronic renal insufficiency. Because the acquisition
      cost of fidaxomicin far exceeds that of metronidazole or vancomycin, in order to
      rationally utilize this agent, it should be targeted to those populations who are
      at high risk for relapse and in whom the drug has demonstrated superiority. In
      this manuscript is reviewed the changing epidemiology of CDI, current treatment
      options for this infection, proposed benefits of fidaxomicin over currently
      available antimicrobial options, available analysis of cost effectiveness of the
      drug, and is given recommendations for judicious use of the drug based upon the
      available published literature. 

PMID- 24587893
TI  - Long-acting muscarinic receptor antagonists for the treatment of chronic airway
      diseases.
AB  - Acetylcholine (neuronal and non-neuronal origin) regulates bronchoconstriction,
      and mucus secretion. It has an inflammatory effect by inducing attraction,
      survival and cytokine release from inflammatory cells. Muscarinic receptors
      throughout the bronchial tree are mainly restricted to muscarinic M1, M2 and M3
      receptors. Three long-acting muscarinic receptor antagonists (LAMAs) were
      approved for the treatment of chronic obstructive pulmonary disease (COPD) in
      Europe: once-daily tiotropium bromide; once-daily glycopyrronium bromide; and
      twice-daily aclidinium bromide. All have higher selectivity for M3 receptors than
      for M2 receptors, and dissociate more slowly from the M3 receptors than they do
      from the M2 receptors. Some LAMAs showed anti-inflammatory effects [inhibition of
      neutrophil chemotactic activity and migration of alveolar neutrophils, decrease
      of several cytokines in the bronchoalveolar lavage (BAL) including interleukin
      (IL)-6, tumor necrosis factor (TNF)-alpha and leukotriene (LT)B4] and
      antiremodeling effects (inhibition of mucus gland hypertrophy and decrease in
      MUC5AC-positive goblet cell number, decrease in MUC5AC overexpression). In the
      clinic, LAMAs showed a significant improvement of forced expiratory volume in 1
      second (FEV1), quality of life, dyspnea and reduced the number of exacerbations
      in COPD and more recently in asthma. This review will focus on the three LAMAs
      approved in Europe in the treatment of chronic airway diseases. 

PMID- 24587894
TI  - Extending single molecule fluorescence observation time by amplitude-modulated
      excitation.
AB  - We present a hardware-based method that can improve single molecule fluorophore
      observation time by up to 1500% and super-localization by 47% for the
      experimental conditions used. The excitation was modulated using an acousto-optic
      modulator (AOM) synchronized to the data acquisition and inherent data conversion
      time of the detector. The observation time and precision in super-localization of
      four commonly used fluorophores were compared under modulated and traditional
      continuous excitation, including direct total internal reflectance excitation of
      Alexa 555 and Cy3, non-radiative Forster resonance energy transfer (FRET) excited
      Cy5, and direct epi-fluorescence wide field excitation of Rhodamine 6G. The
      proposed amplitude-modulated excitation does not perturb the chemical makeup of
      the system or sacrifice signal and is compatible with multiple types of
      fluorophores. Amplitude-modulated excitation has practical applications for any
      fluorescent study utilizing an instrumental setup with time-delayed detectors.

PMID- 24587896
TI  - Prevalence and diversity of avian haematozoan parasites in wetlands of
      bangladesh.
AB  - The parasites of genera Haemoproteus, Plasmodium, and Leucocytozoon are well
      known avian haematozoa and can cause declined productivity and high mortality in
      wild birds. The objective of the study was to record the prevalence of
      haematozoan parasites in a wide range of wetland birds in Bangladesh. Six species
      of Haemoproteus, seven species of Plasmodium, one unidentified species of
      Leucocytozoon, and one unidentified microfilaria of the genus Paronchocerca were
      found. Data on the morphology, size, hosts, prevalence, and infection intensity
      of the parasites are provided. The overall prevalence among the birds was 29.5%
      (95 out of 322 birds). Of those, 13.2% (42 of 319) of birds were infected with
      Haemoproteus spp., 15.1% with Plasmodium spp. (48 of 319) and 0.6% with
      Leucocytozoon spp. (2 of 319). Two birds were positive for both Haemoproteus sp.
      and Plasmodium sp. A single resident bird, Ardeola grayii, was found positive for
      an unidentified microfilaria. Prevalence of infection varied significantly among
      different bird families. Wild birds of Bangladesh carry several types of
      haematozoan parasites. Further investigation with a larger sample size is
      necessary to estimate more accurately the prevalence of haematozoan parasites
      among wild birds as well as domestic ducks for better understanding of the
      disease ecology. 

PMID- 24587895
TI  - Drug-Induced Apoptosis: Mechanism by which Alcohol and Many Other Drugs Can
      Disrupt Brain Development.
AB  - Maternal ingestion of alcohol during pregnancy can cause a disability syndrome
      termed Fetal Alcohol Spectrum Disorder (FASD), which may include craniofacial
      malformations, structural pathology in the brain, and a variety of long-term
      neuropsychiatric disturbances. There is compelling evidence that exposure to
      alcohol during early embryogenesis (4th week of gestation) can cause excessive
      death of cell populations that are essential for normal development of the face
      and brain. While this can explain craniofacial malformations and certain
      structural brain anomalies that sometimes accompany FASD, in many cases these
      features are absent, and the FASD syndrome manifests primarily as neurobehavioral
      disorders. It is not clear from the literature how alcohol causes these latter
      manifestations. In this review we will describe a growing body of evidence
      documenting that alcohol triggers widespread apoptotic death of neurons and
      oligodendroglia (OLs) in the developing brain when administered to animals,
      including non-human primates, during a period equivalent to the human third
      trimester of gestation. This cell death reaction is associated with brain
      changes, including overall or regional reductions in brain mass, and long-term
      neurobehavioral disturbances. We will also review evidence that many drugs used
      in pediatric and obstetric medicine, including general anesthetics (GAs) and anti
      epileptics (AEDs), mimic alcohol in triggering widespread apoptotic death of
      neurons and OLs in the third trimester-equivalent animal brain, and that human
      children exposed to GAs during early infancy, or to AEDs during the third
      trimester of gestation, have a significantly increased incidence of FASD-like
      neurobehavioral disturbances. These findings provide evidence that exposure of
      the developing human brain to GAs in early infancy, or to alcohol or AEDs in late
      gestation, can cause FASD-like neurodevelopmental disability syndromes. We
      propose that the mechanism by which alcohol, GAs and AEDs produce neurobehavioral
      deficit syndromes is by triggering apoptotic death and deletion of neurons and
      OLs (or their precursors) from the developing brain. Therefore, there is a need
      for research aimed at deciphering mechanisms by which these agents trip the
      apoptosis trigger, the ultimate goal being to learn how to prevent these agents
      from causing neurodevelopmental disabilities. 

PMID- 24587897
TI  - Comparative study of the prevalence of intestinal parasites in low socioeconomic
      areas from South chennai, India.
AB  - Intestinal parasites cause one of the most important health problems through
      their effects in causing undernourishment morbidity and incapacitation due to
      their behavior particularly in children compared to adults. This study was
      intended to state the prevalence of intestinal parasites between the slum
      dwellers of different areas in south Chennai. Among the total of 256 samples
      collected between the ages of 0-50 yrs, 194 samples were positive. Standard
      laboratory techniques for parasitological diagnosis were carried out for each
      sample. Entamoeba coli (23%), Cyclospora sp. (22.2%), Entamoeba histolytica
      (21.8%), Giardia intestinalis (14.4%), Ascaris lumbricoides (6.2%), Trichuris
      trichiura (1.1%), and Hymenolepis nana (2.7%) were found in the dwellers of low
      socioeconomic areas. The data on the prevalence of parasites with respect to sex
      and age showed that the females harbored more numbers of parasites when compared
      to males. Further, with respect to age, children and teenagers had surplus
      parasites compared to old age groups. The percentage of educational status showed
      a reduction in the number of parasites in the higher education dwellers. These
      parasites could be prevented by possible grouping of better ecological design and
      hygiene. Conclusively, the examination of personal hygiene as well as routine
      medical examination and treatment is strongly recommended in the low socio
      economic areas. 

PMID- 24587898
TI  - In Vitro Effect of Aqueous Extract and Fraction IV Portion of Ximenia americana
      Stem Bark on Trypanosoma congolense DNA.
AB  - Trypanosomosis is a debilitating disease affecting mainly livestock and humans in
      tropical Africa. Chemically synthesized drugs and medicinal plants have been used
      in the treatment and control of this disease. In this study, the in vitro effect
      of aqueous extracts and fraction IV extract of Ximenia americana stem bark on
      Trypanosoma congolense DNA was investigated. The extracts were incubated with the
      parasites in vitro at 300 mg/mL aqueous extract and 25 mg/mL fraction IV portion
      for 30, 60, and 120 mins. The DNA of the trypanosomes was isolated and digested
      using ECOR1 enzyme and subsequently PCR was carried out. Results showed that
      aqueous extract and fraction IV portion immobilized 55% and 90% of the
      trypanosomes after 30-minute incubation. Subsequent isolation of the parasite DNA
      and agarose gel electrophoresis did not reveal that cell death was as a result of
      DNA fragmentation. This suggests that cell death was by another mechanism of
      action. 

PMID- 24587900
TI  - Remission from Depression among Adults with Arthritis: A 12-Year Followup of a
      Population-Based Study.
AB  - Individuals with arthritis are vulnerable to depression. In this study, we
      calculated time to remission from depression in a representative community-based
      sample of depressed Canadians with arthritis who were followed for 12 years. We
      conducted secondary analysis of a longitudinal panel study, the National
      Population Health Survey, which was begun in 1994/95 and has included biennial
      assessment of depression since that time. Our analysis focused on a total of 216
      respondents with arthritis who were depressed at baseline. The mean time to
      remission from depression was calculated using the Kaplan-Meier procedure and
      compared across categories of each of the potential predictors. The percentage of
      those no longer screening positive for depression was calculated at two years
      after baseline. At two years after baseline, 71% of the sample had achieved
      remission from depression. Time to remission was significantly longer for those
      depressed adults who were under the age of 55, those who reported more chronic
      pain at baseline, those with comorbid migraine, and those who experienced
      childhood physical abuse or parental addictions. These findings highlight the
      importance of screening for these factors to improve the targeting of
      interventions to depressed patients with arthritis. 

PMID- 24587899
TI  - Genes associated with SLE are targets of recent positive selection.
AB  - The reasons for the ethnic disparities in the prevalence of systemic lupus
      erythematosus (SLE) and the relative high frequency of SLE risk alleles in the
      population are not fully understood. Population genetic factors such as natural
      selection alter allele frequencies over generations and may help explain the
      persistence of such common risk variants in the population and the differential
      risk of SLE. In order to better understand the genetic basis of SLE that might be
      due to natural selection, a total of 74 genomic regions with compelling evidence
      for association with SLE were tested for evidence of recent positive selection in
      the HapMap and HGDP populations, using population differentiation, allele
      frequency, and haplotype-based tests. Consistent signs of positive selection
      across different studies and statistical methods were observed at several SLE
      associated loci, including PTPN22, TNFSF4, TET3-DGUOK, TNIP1, UHRF1BP1, BLK, and
      ITGAM genes. This study is the first to evaluate and report that several SLE
      associated regions show signs of positive natural selection. These results
      provide corroborating evidence in support of recent positive selection as one
      mechanism underlying the elevated population frequency of SLE risk loci and
      supports future research that integrates signals of natural selection to help
      identify functional SLE risk alleles. 

PMID- 24587901
TI  - The Association between KIF6 Single Nucleotide Polymorphism rs20455 and Serum
      Lipids in Filipino-American Women.
AB  - The Trp719Arg allele of KIF6 rs20455, a putative risk factor for CHD especially
      in those with elevated low-density lipoprotein cholesterol (LDL-C), was
      investigated in Filipino-American women (FAW, n = 235) participating in health
      screenings in four cities. The rs20455 genotype of each subject was determined by
      a multiplex assay using a Luminex-OLA procedure. The risk allele Trp719Arg was
      present in 77% of the subjects. The genotype distribution was 23% Trp/Trp, 51%
      Arg/Trp, and 26% Arg/Arg. Genotype did not predict the presence of CHD risk
      factors. Moreover, LDL-C, HDL-C, and triglycerides mean values did not vary as a
      function of genotype. However, those with the Arg/Arg genotype on statin
      medication exhibited a significantly higher mean triglycerides level (P < 0.01).
      Approximately 60% of participants regardless of genotype exhibited LDL-C levels
      >=100 mg/dL but were not taking medication. Approximately 43% of those with the
      Trp719Arg risk allele on statins exhibited elevated LDL-C levels. Our study
      suggests that the Trp719Arg allele of KIF 6 rs20455 is common among Filipino
      American women; thus, even with borderline LDL-C levels would benefit from statin
      treatment. Secondly, many participants did not exhibit guideline recommended LDL
      C levels including many who were on statin drugs. 

PMID- 24587902
TI  - Second generation self-inflating tissue expanders: a two-year experience.
AB  - Background. Tissue expansion is a well-established surgical technique that
      produces an additional amount of normal skin to cover a defect. This technique is
      appealing because the skin quality and color are from the patient's own. The
      widely used injectable expanders are of great reliability but carry the
      disadvantage of being painful during injection and most of the time require
      multiple clinic visits. So the idea of self-inflation became attractive and
      hydrogel expanders were developed and became widely known for being painless
      during clinic visit and decrease number of visits. The first generation expanders
      were modified by adding an enclosing plastic shell to decrease the unopposed
      expansion that occurred in the first generation expanders, which lead to pressure
      necrosis of the skin flaps. This made it an attractive option for tissue
      expansion in children and some adult patients. Patients, Materials, and Methods.
      Charts of 17 patients were retrospectively reviewed, all of them had second
      generation self-inflating expanders implanted over a 2-year period for one of two
      purposes, the treatment of giant nevi or burn scars. Results. Fifteen patients
      were females and 2 were males. The indication was large burn scar in 14 cases
      (14/17), in which 47/55 expanders were implanted, and giant nevus in 3/17 cases
      in which 8/55 expanders were implanted. Extrusion of the expander occurred in
      8/55 expanders (14.5%), which occurred in 6/14 patients. The highest percentage
      of extrusion occurred in the neck in which two out of three expanders extruded;
      otherwise this complication does not seem to be related to the indication,
      gender, nor age of the patients. It seems to be that it is technical in nature.
      The patients did not have to get any injections to fill the tissue expanders,
      which made the expansion process less painful and more convenient. Conclusion.
      This seems to be currently the largest published review in which second
      generation expanders were used. Those expanders seem to offer a desirable
      advantage of being painless for children, also they do not require repeated
      visits to the surgeon's clinic, which is of great value for patients living in
      the periphery. 

PMID- 24587903
TI  - Coronary spasm in neurosurgical patients and role of trigeminocardiac reflex.
AB  - Background. Coronary artery spasm (CAS) is a rarely reported complication in
      neurosurgical patients and its main causative mechanism was attributed to vagal
      mediated responses. However, these may be the unusual manifestations of
      trigeminal cardiac reflex (TCR) which is a well established brain stem reflex
      observed in various neurosurgical patients. Methods and Results. In this review,
      we have searched for the case reports/papers related to intraoperative coronary
      spasm in neurosurgical patients and described the role of TCR in this regard. TCR
      is a possible mechanism in producing CAS in most of the cases in which
      stimulation occurred at or near the vicinity of trigeminal nerve. It is likely
      that TCR mediated coronary spasm may be a physiological mechanism and not related
      to actual myocardial insult apparent by cardiac enzymes or echocardiography
      studies in most of the cases. Some common risk factors may also exist related to
      occurrence of CAS as well as TCR. Conclusions. In conclusion, neurosurgical
      procedures occurring at the vicinity of trigeminal nerve may produce CAS even in
      previously healthy patients and may produce catastrophic consequences. There is a
      need for future reports and experimental studies on the interaction of TCR and
      pathophysiological mechanisms related to CAS. 

PMID- 24587904
TI  - Antibiogram for haemodialysis catheter-related bloodstream infections.
AB  - Background. Haemodialysis (HD) catheter-related bloodstream infections (CRBSIs)
      are a major complication of long-term catheter use in HD. This study identified
      the epidemiology of HD CRBSIs and to aid in the choice of empiric antibiotics
      therapy given to patients with HD CRBSIs. Methods. Patients with HD CRBSIs were
      identified. Their blood cultures were performed according to standard sterile
      technique. Specimens were sent to the microbiology lab for culture and
      sensitivity testing. Results were tabulated in antibiograms. Results. 18 patients
      with a median age of 61.0 years (IQR: 51.5-73.25) were confirmed to have HD
      CRBSIs based on our study criteria. Eight (44.4%) patients had gram-negative
      infections, 7 (38.9%) patients gram-positive infections, and 3 (16.7%) patients
      had polymicrobial infections. We noted that most of the gram-negative bacteria
      were sensitive to ceftazidime. Unfortunately, cloxacillin resistance was high
      among gram-positive organisms. Coagulase-negative Staphylococcus and Bacillus sp.
      were the most common gram-positive organisms and they were sensitive to
      vancomycin. Conclusion. Our study revealed the increased incidence of gram
      negative organism in HD CRBSIs. Antibiogram is an important tool in deciding
      empirical antibiotics for HD CRBSIs. Tailoring your antibiotics accordingly to
      the antibiogram can increase the chance of successful treatment and prevent the
      emergence of bacterial resistance. 

PMID- 24587906
TI  - Is Repeat PTA of a Failing Hemodialysis Fistula Durable?
AB  - Purpose. Our objective was to evaluate the outcome of percutaneous transluminal
      angioplasty (PTA) and particularly rePTA in a failing arteriovenous fistula (AV
      fistula). Are multiple redilations worthwhile? Patients and Methods. All 159
      stenoses of AV fistulas that were treated with PTA, with or without stenting,
      during 2008 and 2009, were included. Occluded fistulas that were dilated after
      successful thrombolysis were also included. Median age was 68 (interquartile
      range 61.5-78.5) years and 75% were male. Results. Seventy-nine (50%) of the
      primary PTAs required no further reintervention. The primary patency was 61% at 6
      months and 42% at 12 months. Eighty (50%) of the stenoses needed at least one
      reintervention. Primary assisted patency (defined as patency after subsequent
      reinterventions) was 89% at 6 months and 85% at 12 months. The durability of
      repeated PTAs was similar to the durability of the primary PTA. However, an early
      primary PTA carried a higher risk for subsequent reinterventions. Successful
      dialysis was achieved after 98% of treatments. Nine percent of the stenoses
      eventually required surgical revision and 13% of the fistulas failed permanently.
      Conclusion. The present study suggests that most failing AV-fistulas can be
      salvaged endovascularly. Repeated PTA seems similarly durable as the primary PTA.

PMID- 24587905
TI  - Gray matters in multiple sclerosis: cognitive impairment and structural MRI.
AB  - Multiple sclerosis (MS) is an immune-mediated disease affecting central nervous
      system (CNS). Although MS is classically considered a white matter (WM) disease,
      the involvement of gray matter (GM) in the pathogenic process has been confirmed
      by pathology studies and MRI studies. Impairment of cognitive domains such as
      memory, mental processing speed, attention, and executive function can occur from
      the early stage of the disease and tends to worsen over time, despite stable
      physical symptoms. WM demyelination is moderately correlated with CI, suggesting
      that probably WM abnormalities alone cannot fully explain the extent of clinical
      symptoms in MS, including CI. Several MRI techniques have shown the involvement
      of GM in MS and the association between GM damage, physical disability, and CI.
      The aim of this review is to provide an overview of CI and GM damage assessed by
      structural brain MRI. 

PMID- 24587907
TI  - Myelonecrosis: A Clinicopathological Study from a Tertiary Care Center in South
      India over a Twelve-Year Period.
AB  - Aims. To study the etiology, diagnostic features, and clinical significance of
      myelonecrosis. Methods. A retrospective review of all trephine biopsies done over
      12 years (January 2000 to December 2012) in Department of pathology was done and
      all trephine biopsies showing MN were identified and studied. Results. Twenty
      five cases accounting for 0.4% were identified. Fever and generalized weakness
      were the common presenting symptoms. Anemia was seen in all cases followed by
      thrombocytopaenia. Malignancy was the underlying cause in 64% of cases;
      hematolymphoid malignancy was seen in two-thirds and solid malignancies in one
      third of the cases. Tuberculosis accounted for 16% of the cases and the etiology
      was unknown in 12%. Conclusions. The causes of MN are varied and hematological
      malignancy and solid malignancies are the most common causes. Presence of
      myelonecrosis is associated with a poor prognosis. Myelonecrosis may obscure the
      underlying disorder and hence a thorough search in the bone marrow biopsy itself
      with the help of immunohistochemistry may prove worthwhile in identifying the
      underlying disease. 

PMID- 24587908
TI  - Primary Zonal High Intensity Focused Ultrasound for Prostate Cancer: Results of a
      Prospective Phase IIa Feasibility Study.
AB  - OBJECTIVES: To present the results of a prospective phase IIa study assessing the
      role of primary zonal High Intensity Focused Ultrasound (HIFU) for prostate
      cancer treatment. METHODS: 31 consecutive patients with unilateral organ confined
      prostate cancer primarily treated by zonal HIFU (from February 2007 to June 2011)
      were recruited into a single centre prospective phase IIa feasibility study.
      Complications were prospectively recorded and graded according to the Clavien
      Dindo score. Postoperatively, patients were followed with serial serum PSA
      determinations and digital rectal examinations. An individual PSA nadir was
      identified in each patient. Followup also included whole gland biopsies performed
      in the event of a PSA rising>2.0 ng/mL above nadir value (Phoenix criteria).
      RESULTS: At a median followup of 38 months, biochemical recurrence free survival
      was 100%, 89%, and 82.7% at 1, 2, and 3 years, respectively, with overall and
      cancer specific survival of 100%. The procedure was safe and well tolerated with
      no major adverse events. All patients were continent at their last followup and
      55.2% (16/29) had erectile function sufficient for penetration. CONCLUSION:
      Primary zonal HIFU is a valid focal therapy strategy, safe and feasible in day to
      day practice with good promising results [corrected].

PMID- 24587909
TI  - Solid State Fermentation of a Raw Starch Digesting Alkaline Alpha-Amylase from
      Bacillus licheniformis RT7PE1 and Its Characteristics.
AB  - The thermodynamic and kinetic properties of solids state raw starch digesting
      alpha amylase from newly isolated Bacillus licheniformis RT7PE1 strain were
      studied. The kinetic values Q p , Y p/s , Y p/X , and q p were proved to be best
      with 15% wheat bran. The molecular weight of purified enzyme was 112 kDa. The
      apparent K m and V max values for starch were 3.4 mg mL(-1) and 19.5 IU mg(-1)
      protein, respectively. The optimum temperature and pH for alpha -amylase were 55
      degrees C, 9.8. The half-life of enzyme at 95 degrees C was 17h. The activation
      and denaturation activation energies were 45.2 and 41.2 kJ mol(-1), respectively.
      Both enthalpies (DeltaH (*)) and entropies of activation (DeltaS (*)) for
      denaturation of alpha -amylase were lower than those reported for other
      thermostable alpha -amylases. 

PMID- 24587910
TI  - A New Diagnostic Way for Behcet's Disease: Skin Prick with Self-Saliva.
AB  - Behcet's disease (BD) is a mysterious multisystemic disorder characterized by
      recurrent involvement of mucocutaneous (including recurrent aphthous stomatitis;
      RAS), ocular, intestinal, vascular, and/or nervous system organs. Previously, the
      positivity of "pathergy test", which is one of the diagnostic examinations, was
      reported to be related to the possession of HLA-B51 gene in BD patients, even
      though the positivity is low and different from the countries. Here, instead of
      the ordinal pathergy test, we would like to propose the prick with self-saliva as
      a new diagnostic way for patients with RAS of BD based on the genetic intrinsic
      factors including HLA-B51 and extrinsic triggering factors. BD patients are
      considered to acquire the hypersensitivity against oral streptococci through the
      innate immune mechanism in the oral cavity. Bes-1 gene and 65 kD of heat shock
      protein (HSP-65) derived from oral S. sanguinis are supposed to play important
      roles as extrinsic factors in BD pathogenesis. Although the prick positivity was
      not related to the possession of HLA-B51 gene, the method is suggested to be a
      significant way for BD diagnosis. The results also suggest that BD symptoms are
      due to the vascular immune responses by monocytes expressed oral streptococcal
      agents of the patients. 

PMID- 24587911
TI  - Sleep Quality and Quality of Life in COPD Patients with and without Suspected
      Obstructive Sleep Apnea.
AB  - Present study was designed to obtain association between sleep apnea with sleep
      quality and quality of life in COPD patients. This cross-sectional descriptive
      study was conducted on 139 patients with COPD in a chest clinic of a university
      hospital. All patients were evaluated by pulmonary function test for
      determination of severity of their disease. Also, Berlin questionnaire, Epworth
      sleepiness scale, Pittsburgh Sleep Quality Index, and St. George Respiratory
      questionnaires (SGRQ) were employed for assessment of patients. Analysis of data
      showed that quality of sleep was significantly correlated with quality of life (P
      < 0.001). About half of the patients were at high risk for sleep apnea. The
      patients were divided into two groups according to the result of Berlin
      questionnaire. Significant differences were found between the groups for total
      score and each of three subscores of SGRQ suggesting worse quality of life in
      overlap syndrome (P < 0.001). Also, patients with overlap syndrome had worse
      quality of sleep compared to patients without it (8.1 +/- 1.7 versus 6.2 +/- 2.3;
      P < 0.001). Stepwise multiple regression analysis showed that severity of COPD,
      coexisting obstructive sleep apnea, and sleep quality accounted for the SGRQ
      significantly (r (2) (coefficient of determination) = 0.08, 0.21, and 0.18,
      resp.). It is recommended that patient with COPD be evaluated for sleep apnea and
      sleep disorders during routine examinations and followups. 

PMID- 24587912
TI  - Daytime sleepiness in Parkinson's disease: perception, influence of drugs, and
      mood disorder.
AB  - Parkinson's disease (PD) is associated with sleep complaints as excessive daytime
      sleepiness (EDS) and several factors have been implicated in the genesis of these
      complaints. Objective. To correlate the subjective perception of EDS with
      variables as the severity of the motor symptoms, medications, and the presence of
      depressive symptoms. Materials and Methods. A cross-sectional study, using
      specific scales as Epworth sleepiness scale (ESS), Beck depression inventory
      (iBeck) and Hoehn and Yahr (HY), in 42 patients with PD. Results. The patients
      had a mean age of 61.2 +/- 11.3 years and mean disease duration of 4.96 +/- 3.3
      years. The mean ESS was 7.5 +/- 4.7 and 28.6% of patients reached a score of
      abnormally high value (>10). There was no association with gender, disease
      duration, and dopamine agonists. Patients with EDS used larger amounts of
      levodopa (366.7 +/- 228.0 versus 460.4 +/- 332.25 mg, P = 0.038), but those who
      had an iBeck >20 reached lower values of ESS than the others (5.9 +/- 4.1 versus
      9.3 +/- 4.8, P = 0.03). Conclusions. EDS was common in PD patients, being related
      to levodopa intake. Presence of depressed mood may influence the final results of
      self-assessment scales for sleep disorders. 

PMID- 24587913
TI  - The prevalence of tonsilloliths and other soft tissue calcifications in patients
      attending oral and maxillofacial radiology clinic of the university of iowa.
AB  - Objective. The purpose of this study was to determine the prevalence of
      tonsiliths in patients attending the oral and maxillofacial radiology clinic of
      The University of Iowa and to determine if there is any correlation between the
      presence of tonsiliths and the presence of stones in other body tissues, ducts,
      or organs. Study Design. This was a two-part study. The first part was a
      prevalence study whereas the second was a matched pair case-control study. The
      matched pair case-control study commenced after the prevalence study was
      concluded. No new or unusual radiographs were made in this study. The study only
      reviewed radiographs that were made for clinical purposes. Results. A total of
      1524 pantomographs were reviewed and 124 subjects (53 males and 71 females) aged
      9 years and 2 months to 87 years (mean age 52.6 years) were included for data
      analysis. Thirty-eight subjects had single tonsiliths whereas 86 subjects had
      multiple tonsiliths. The prevalence of tonsiliths in the study population was
      8.14%. A total of 20 subjects were included in the second part of the study,
      comprising 10 each for matched pair case-control groups. The observations did not
      indicate any correlation between the presence of tonsiliths and the presence of
      stones in other body tissues, ducts, or organs. Conclusion. The prevalence of
      tonsiliths in our study population was 8.14%. The observations in our study do
      not support any correlations between tonsiliths and calcifications in other body
      tissues, organs, or ducts. 

PMID- 24587914
TI  - p16 Expression Is Lost in Severely Atypical Cellular Blue Nevi and Melanoma
      Compared to Conventional, Mildly, and Moderately Atypical Cellular Blue Nevi.
AB  - Background. Significant decreases in p16 expression have been shown to occur in
      melanoma compared to Spitz tumors, and loss of p16 staining has been found to
      correlate with melanoma tumor progression. However, comparison of p16 between
      atypical cellular blue nevi (CBN) and melanoma has not been reported previously.
      Methods. p16 immunohistochemical staining was evaluated in 14 atypical CBN, 8
      conventional and atypical melanocytic nevi, and 16 melanomas, including 4
      malignant CBN. p16 staining intensity was graded on a scale of 0-3 and the
      percentage of melanocytes stained with p16 was determined. Results. p16 staining
      was significantly higher in all CBN as a group when compared to melanomas (P =
      0.001) and malignant CBN (P = 0.00008). Higher p16 expression was also seen in
      mildly (P = 0.0002) and moderately atypical (P = 0.02), but not severely
      atypical, CBN compared to melanomas. Conclusions. p16 immunohistochemical
      expression is higher in mildly and moderately atypical CBN compared to severely
      atypical CBN and melanomas. In conjunction with additional markers and histology,
      p16 staining may be useful in confirming the benign nature of these tumors, but
      is not useful in distinguishing severely atypical CBN from malignant cases,
      consistent with the overlapping histologic features between these tumors. 

PMID- 24587916
TI  - Antioxidant effects of bovine lactoferrin on dexamethasone-induced hypertension
      in rat.
AB  - Dexamethasone- (Dex-) induced hypertension is associated with enhanced oxidative
      stress. Lactoferrin (LF) is an iron-binding glycoprotein with antihypertensive
      properties. In this study, we investigated the effect of chronic administration
      of LF on oxidative stress and hypertension upon Dex administration. Male Wistar
      rats were treated by Dex (30  MU g/kg/day subcutaneously) or saline for 14 days.
      Oral bovine LF (30, 100, 300 mg/kg) was given from day 8 to 14 in a reversal
      study. In a prevention study, rats received 4 days of LF treatment followed by
      Dex and continued during the test period. Systolic blood pressure (SBP) was
      measured using tail-cuff method. Thymus weight was used as a marker of
      glucocorticoid activity. Plasma hydrogen peroxide (H2O2) concentration and ferric
      reducing antioxidant power (FRAP) value were determined. Dexamethasone
      significantly increased SBP and plasma H2O2 level and decreased thymus and body
      weights. LF lowered (P < 0.01) and dose dependently prevented (P < 0.001) Dex
      induced hypertension. LF prevented body weight loss and significantly reduced the
      elevated plasma H2O2 and increased FRAP values. Chronic administration of LF
      strongly reduced the blood pressure and production of ROS and improved
      antioxidant capacity in Dex-induced hypertension, suggesting the role of
      inhibition of oxidative stress as another mechanism of antihypertensive action of
      LF. 

PMID- 24587917
TI  - Prevalence of Anti-JC Virus Antibody in Multiple Sclerosis Patients in Kuwait.
AB  - Background. Multiple sclerosis (MS) therapeutics entered a new era after the
      development of anti-JC virus (anti-JCV) antibody assay that assesses the risk of
      development of progressive multifocal leukoencephalopathy (PML) in patients
      treated with natalizumab. Objective. To determine the prevalence of anti-JCV
      antibody among MS patients in Kuwait. Methods. Using the national MS registry,
      demographics and disease characteristics of MS patients who were screened for
      anti-JC virus antibody were collected. The prevalence of anti-JCV antibody
      seropositivity and its association with demographic and disease characteristics
      were evaluated. Results. Out of 110 screened MS patients for anti-JCV antibodies,
      65.5% were females. Mean age and disease duration were 29.23 +/- 8.55 and 5.39 +/
      5.04 years, respectively. 47.3% of patients were already on natalizumab and
      52.7% of patients were screened for stratification to either natalizumab or a
      different Disease Modifying Therapy (DMT). The overall prevalence of anti-JC
      virus antibody was 40%. Gender (P = 0.69), disease duration (P = 0.11), and
      number of natalizumab infusions (P = 0.64) were not associated with
      seropositivity. Patients aged >=30 years were more likely to be seropositive (P =
      0.01). Conclusion. The prevalence of anti-JCV antibody is slightly lower than
      what is reported in published studies. Seropositivity was associated with an
      increasing age of MS patients. 

PMID- 24587915
TI  - Vitamin D and the Immune System from the Nephrologist's Viewpoint.
AB  - Vitamin D and its analogues are widely used as treatments by clinical
      nephrologists, especially when treating chronic kidney disease (CKD) patients
      with secondary hyperparathyroidism. As CKD progresses, the ability to compensate
      for elevations in parathyroid hormone (PTH) and fibroblast growth factor-23 and
      for decreases in 1,25(OH)2D3 becomes inadequate, which results in
      hyperphosphatemia, abnormal bone disorders, and extra-skeletal calcification. In
      addition to its calciotropic effect on the regulation of calcium, phosphate, and
      parathyroid hormone, vitamin D has many other noncalciotropic effects, including
      controlling cell differentiation/proliferation and having immunomodulatory
      effects. There are several immune dysregulations that can be noted when renal
      function declines. Physicians need to know well both the classical and
      nonclassical functions of vitamin D. This review is an analysis from the
      nephrologist's viewpoint and focuses on the relationship between the vitamin D
      and the immune system, together with vitamin's clinical use to treat kidney
      diseases. 

PMID- 24587918
TI  - Dopamine D2R Agonist-Induced Cardiovascular Effects in Healthy Male Subjects:
      Potential Implications in Clinical Settings.
AB  - Dopamine D2 receptor agonists represent a first line treatment option in young
      patients with signs and symptoms of idiopathic Parkinson's disease. An
      association between the use of D2 receptor agonists in Parkinson's disease
      patients and heart failure has been reported. The identification of the
      underlying mechanism is needed to minimize the resultant cardiovascular
      morbidity. In a phase I clinical trial, a D2 receptor agonist (pramipexole) was
      administered to 52 healthy male subjects following a dose escalation scheme.
      Serial measurements of resting blood pressure, heart rate, and derived parameters
      including pulse pressure, pulsatile stress, and rate pressure product were
      analysed. Statistically significant and clinically relevant increases in most of
      the assessed parameters were found. Ten subjects were removed prematurely from
      the trial because of clinically significant increases in blood pressure and/or
      heart rate requiring immediate intervention with IV rescue medications including
      a selective beta -1 blocker. The observed drug-related changes in vital signs
      were of clinical relevance and might explain some of the cardiovascular morbidity
      reported in patients receiving D2 receptor agonist in clinical settings. We
      suggest that the additional use of a beta -1 blocking agent might mitigate the
      risk of cardiovascular morbidity among patients receiving long-term D2 receptor
      agonists. 

PMID- 24587919
TI  - Treatment planning methods in high dose rate interstitial brachytherapy of
      carcinoma cervix: a dosimetric and radiobiological analysis.
AB  - Treatment planning is a trial and error process that determines optimal dwell
      times, dose distribution, and loading pattern for high dose rate brachytherapy.
      Planning systems offer a number of dose calculation methods to either normalize
      or optimize the radiation dose. Each method has its own characteristics for
      achieving therapeutic dose to mitigate cancer growth without harming contiguous
      normal tissues. Our aim is to propose the best suited method for planning
      interstitial brachytherapy. 40 cervical cancer patients were randomly selected
      and 5 planning methods were iterated. Graphical optimization was compared with
      implant geometry and dose point normalization/optimization techniques using
      dosimetrical and radiobiological plan quality indices retrospectively. Mean tumor
      control probability was similar in all the methods with no statistical
      significance. Mean normal tissue complication probability for bladder and rectum
      is 0.3252 and 0.3126 (P = 0.0001), respectively, in graphical optimized plans
      compared to other methods. There was no significant correlation found between
      Conformity Index and tumor control probability when the plans were ranked
      according to Pearson product moment method (r = -0.120). Graphical optimization
      can result in maximum sparing of normal tissues. 

PMID- 24587920
TI  - Maxillofacial fractures in the province of pescara, Italy: a retrospective study.
AB  - The aim of the present study was to assess the etiology and pattern of
      maxillofacial fractures in the Province of Pescara, Abruzzo, Central Italy. Was
      performed a retrospective review of patients treated at the Department of
      Maxillofacial Surgery of Spirito Santo Hospital from January 2010 to December
      2012. Data collected and analyzed included sex, age, cause of injury, site of
      fracture, monthly distribution, and alcohol misuse. A total of 306 patients
      sustaining 401 maxillofacial fractures were treated. There were 173 males (56.5%)
      and 133 females (43.5%). Most of the patients (36.9%) were in the age group of 18
      44 years. The most common causes of injuries were road traffic accidents (26.4%);
      the second leading cause was interpersonal violence (23.2%), followed by injuries
      associated with falls (19.2%). Fractures of the mandible (31%) and zygoma (23%)
      were the most common maxillofacial fractures in our study. The monthly
      distribution peaked in the summer (July and August, 30.4%) and in October
      (13.1%). In conclusion, this study confirms the close correlation between the
      incidence and etiology of facial fractures and the geographical, cultural, and
      socioeconomic features of a population. The data obtained provide important
      information for the design of future plans for injury prevention and for
      education of citizens. 

PMID- 24587921
TI  - Cytoreductive nephrectomy for metastatic renal cell carcinoma: a review of the
      historical literature and its role in the era of targeted molecular therapy.
AB  - Renal cell carcinoma presents with metastatic disease in approximately 30% cases.
      While surgical intervention remains the standard of care for organ confined
      disease, its role is limited in the management of metastatic disease. Over the
      last decade, cytoreductive nephrectomy prior to immunotherapy has demonstrated
      significant improvement in overall survival for appropriately selected patients.
      This review summarizes the evidence for the role of cytoreductive nephrectomy in
      combination with immunotherapy and discusses its potential role in the current
      era of targeted molecular therapy. 

PMID- 24587922
TI  - Sarcomatoid variant of urothelial carcinoma (carcinosarcoma, spindle cell
      carcinoma): a review of the literature.
AB  - Background. Sarcomatoid variant of urothelial carcinoma (SVUC) was added to the
      WHO classification in 2004. Aims. To review the literature. Materials and Method.
      Various internet databases were used. Result. SVUCs are rare biphasic malignant
      neoplasms exhibiting morphologic/immunohistochemical evidence of epithelial and
      mesenchymal differentiation with the presence or absence of heterologous
      elements. Some cases of SVUC have been associated with radiation therapy and
      cyclophosphamide treatment. Patients' ages range from 50 to 77 years (mean age
      66). Patients tend to be younger and they more commonly presented with high-grade
      histology and advanced stage disease, in comparison with patients who had
      conventional urothelial carcinoma (CUC). Results of molecular/genetic studies
      strongly argue for a common monoclonal cell origin of both the epithelial and
      mesenchymal components in SUVC. The cancer specific survival of SVUC is poor in
      comparison with CUC. Radical surgical excision and chemoradiation may be
      associated with improved prognosis; chemoradiation as an organ preserving
      alternative to radical excision may be associated with improved outcome. There is
      no consensus opinion on the best treatment modalities for SUVC. Conclusions. SVUC
      is rare and is associated with inferior outcome compared with CUC. A multicentre
      trial of various treatment options is required. Cases of SVUC should be reported.

PMID- 24587923
TI  - Ultrasound-guided multiple peripheral nerve blocks in a superobese patient.
AB  - The number of obese patients has increased dramatically worldwide. Morbid obesity
      is associated with an increased incidence of medical comorbidities and restricts
      the application choices in anesthesiology. We report a successfully performed
      combined ultrasound-guided blockade of the femoral, tibial, and common peroneal
      nerve in a superobese patient. We present a case report of a 31-year-old, ASA-PS
      II, super obese man (190 kg, 180 cm, BMI: 58 kg/m(2)) admitted to the emergency
      department with a type II segmental tibia shaft fracture and ankle dislocation
      after a vehicle accident. After two failed spinal anesthesia attempts, we decided
      to apply a femoral block combined with a sciatic block. Femoral blocks were
      successfully performed with US guided in-plane technique. Separate blocks of the
      tibial and common peroneal nerves were planned after the sciatic nerve could not
      be located due to the thick subcutaneous tissue. We performed a tibial nerve
      block at 2 cm above the popliteal crease and common peroneal nerve at the level
      of the fibular head with US guided in-plane technique. The blocks were successful
      and no block-related complications were noted. Ultrasound guidance allows new
      approaches for multiple peripheral nerve blocks with low local anesthetic doses
      in obese patients. 

PMID- 24587924
TI  - Unusual length of pedicle: pedunculated squamous papilloma of uvula causing
      unusual Dysphagia of long duration in a child of 10 years.
AB  - Benign oropharyngeal tumors are far less common compared to malignant tumors.
      Oropharyngeal papilloma is present in adults. Squamous papillomas are exophytic
      masses of oral cavity. When they occur on the palate they are most often
      asymptomatic and benign. Pedunculated squamous papillomas usually arise from the
      soft palate, tonsil, or the epiglottis. These lesions can sometimes prove to be
      fatal. A case of pedunculated squamous papilloma, arising from the
      laryngopharynx, the clinical presentation, the site of origin, and the size of
      the lesion were quite unusual. The narrow base of the pedicle made the intraoral
      excision possible. But here, we present a case of a 10-year-old boy who had
      history of dysphagia of 3-year duration for solid food and he was comfortable
      only in squatting position the reason being squamous papilloma of uvula (unusual
      site) atypically because of astonishing length of pedicle (2.3 inches). 

PMID- 24587925
TI  - First Birth after Sperm Selection through Discontinuous Gradient Centrifugation
      and Artificial Insemination from a Chromosomal Translocation Carrier.
AB  - Introduction. Balanced chromosomal carriers, though usually healthy, are
      confronted with recurrent spontaneous abortions and malformations in the
      offspring. Those are related to the transmission of an abnormal, chromosomally
      unbalanced genotype. We evidenced that the proportion of unbalanced spermatozoa
      can be significantly decreased through a sperm preparation process called
      discontinuous gradient centrifugation (DGC). We therefore started offering
      intrauterine inseminations with this procedure to couples with a male
      translocation carriers. Case Presentation. We report the case of a 37-year-old
      man carrying a t(3;10)(q25;p13) reciprocal translocation. He and his partner had
      had trouble conceiving for ten years and had four spontaneous abortions. DGC in
      this patient decreased the proportion of unbalanced spermatozoa from 63.6% to
      52.3%. They were therefore offered intrauterine insemination with DGC, which
      eventually led to the birth of a healthy female child carrying the paternal
      translocation. Conclusion. We showed that translocation carriers could be offered
      intrauterine inseminations with DGC. Before this, the only two options were
      natural conception with prenatal diagnosis and termination of chromosomally
      unbalanced fetuses or preimplantation genetic diagnosis, which is a much heavier
      and costly procedure. We are currently offering this option through a
      multicentric program in France, and this is the first birth originating from it. 

PMID- 24587926
TI  - Recurrent and progressive abdominal pain and enteritis in a Japanese patient with
      paroxysmal nocturnal hemoglobinuria.
AB  - This case report describes a young male patient with recurrent abdominal pain
      persisting for more than 16 months. Clinical investigations showed signs of
      inflammation and pancytopenia. A diagnosis of paroxysmal nocturnal hemoglobinuria
      (PNH) was made 9 months after the onset of the abdominal pain, following
      endoscopic examinations that revealed evidence of a previously unknown
      hemorrhage. Regular monitoring indicated that the abdominal pain was associated
      with elevations in lactate dehydrogenase, C-reactive proteins, and D-dimer
      levels. The patient started treatment with the complement inhibitor eculizumab
      shortly after it was approved for use in Japanese PNH patients with hemolysis.
      Resolution of the abdominal pain and normalization of clinical parameters were
      noted within 3 weeks from treatment initiation. 

PMID- 24587928
TI  - Nontraumatic fracture of the femoral condylar prosthesis in a total knee
      arthroplasty leading to mechanical failure.
AB  - This paper reports a case of fatigue fracture of the femoral component in a
      cruciate-retaining cemented total knee arthroplasty (TKA). A 64-year-old man had
      undergone a primary TKA for osteoarthritis 10 years previously at another
      institution using the PFC-Sigma prosthesis. The patient recovered fully and was
      back to his regular activities. He presented with a history of sudden onset pain
      and locking of the left knee since the preceding three months. There was no
      history of trauma, and the patient was mobilizing with difficulty using crutches.
      Radiographs revealed fracture of the posterior condyle of the femoral prosthesis.
      Revision surgery was performed as an elective procedure revealing the broken
      prosthesis. The TC3RP-PFC revision prosthesis was used with a medial parapatellar
      approach. The patient recovered fully without any squeal. Mechanical failure of
      the knee arthroplasty prosthesis is rare, and nontraumatic fracture of the
      femoral metallic component has not been reported before. 

PMID- 24587927
TI  - Five cases of non-hodgkin B-cell lymphoma of the ovary.
AB  - The involvement of the ovary in lymphomatous process is rare. Such an involvement
      may occur in 2 ways, primary or secondary. We report 5 cases of ovarian non
      Hodgkin's lymphoma, with 3 of which primarily arising in the ovaries. Ovarian
      lymphoma can mimic more frequently occurring tumors including advanced epithelial
      carcinoma and radical surgery may be performed instead of a biopsy. The
      immunophenotypic and clinicopathologic features exhibited in this small series
      are described to call attention to early diagnosis and treatment of ovarian
      lymphoma. All patients were diagnosed as having DLBCL after ovary biopsy.
      Different treatment modalities were used and prognosis of the patients was
      reported. 

PMID- 24587929
TI  - Brooke-spiegler syndrome: a rare entity.
AB  - Brooke-Spiegler syndrome is a rare entity. It is an autosomal dominant syndrome
      in which multiple trichoepitheliomas, cylindromas, or other adnexal tumors are
      seen. Very few cases of Brooke-Spiegler syndrome are reported in the literature.
      We came across a 40 -year-old female in which multiple trichoepitheliomas and
      cylindromas were seen on scalp. In view of clinical history and histopathological
      examination it was diagnosed as Brooke-Spiegler syndrome. We report this case
      because of its rarity. 

PMID- 24587930
TI  - Rhabdomyosarcoma with pseudolipoblasts arising in ovarian carcinosarcoma: a
      distinctive postchemotherapy morphologic variant mimicking pleomorphic
      liposarcoma.
AB  - We describe a case of ovarian carcinosarcoma occurring in a 60-year-old female.
      The neoplasm was excised after neoadjuvant chemotherapy and contained a
      predominant heterologous pleomorphic rhabdomyosarcomatous component in which
      there were numerous multivacuolated rhabdomyoblasts that strongly mimicked
      lipoblasts. The clear cell variant of rhabdomyosarcoma is rarely documented, but
      this case shows a highly unusual finding in which the rhabdomyoblasts show the
      prominent multivacuolation with nuclear indentation characteristic of and
      indistinguishable from pleomorphic lipoblasts. This appears to represent a
      posttreatment phenomenon. As this finding might conceivably occur in other
      rhabdomyosarcomas after chemotherapy, we highlight the potential for diagnostic
      confusion with pleomorphic liposarcoma, which is usually diagnosed by morphology
      so that immunohistochemistry for muscle markers might not be performed. 

PMID- 24587931
TI  - Role of fine needle aspiration in the diagnosis of the rare disease of langerhans
      cell histiocytosis in a child.
AB  - Langerhan's cell histiocytosis (LCH) results from the proliferation of
      immunophenotypically and functionally immature, morphologically rounded
      Langerhan's cells along with eosinophils, macrophages, lymphocytes, and,
      commonly, multinucleated giant cells. Here we report a case in a 6-year-old boy
      of differential diagnoses including dermatopathic lymphadenitis (DL), parasitic
      infection, Kimura's disease, hypersensitivity reactions, cat-scratch disease,
      sinus histiocytosis with massive lymphadenopathy (SHML), hyperplasic lymph nodes,
      and lymphoma. 

PMID- 24587932
TI  - A treatable neurometabolic disorder: glutaric aciduria type 1.
AB  - Glutaric aciduria type 1 (GA-1) is an autosomal recessive disorder of lysine,
      hydroxylysine, and tryptophan metabolism caused by deficiency of glutaryl-CoA
      dehydrogenase. It results in the accumulation of 3-hydroxyglutaric and glutaric
      acid. Affected patients can present with brain atrophy and macrocephaly and with
      acute dystonia secondary to striatal degeneration in most cases triggered by an
      intercurrent childhood infection with fever between 6 and 18 months of age. We
      report two such cases with macrocephaly, typical MRI pictures, and tandem mass
      spectrometry suggestive of glutaric aciduria type 1. 

PMID- 24587933
TI  - Clozapine-induced myocarditis: is mandatory monitoring warranted for its early
      recognition?
AB  - Clozapine is an atypical antipsychotic used for treatment resistant
      schizophrenia. Its potential to induce agranulocytosis is well known but it can
      also cause myocarditis. Clozapine is the only antipsychotic known to induce this
      side effect, typically early in the treatment, and literature is scarce on this
      condition. We are presenting a case report of a 21-year-old schizophrenic male
      who developed myocarditis within 3 weeks of starting on clozapine for his
      treatment resistant psychosis. We then aim to review some of the available
      literature and raise awareness among physicians as this condition can potentially
      be fatal if not detected early. 

PMID- 24587934
TI  - Effectiveness of saikokaryukotsuboreito (herbal medicine) for antipsychotic
      induced sexual dysfunction in male patients with schizophrenia: a description of
      two cases.
AB  - Antipsychotics sometimes cause sexual dysfunction in people with schizophrenia.
      The authors report the effectiveness of Saikokaryukotsuboreito (Japanese
      traditional herbal medicine, Chai-Hu-Jia-Long-Gu-Mu-Li-Tang in Chinese) for
      antipsychotic-induced sexual dysfunction in two male patients with schizophrenia.
      The first patient was a 28-year-old man with schizophrenia who suffered erectile
      dysfunction induced by olanzapine 10 mg/day; the erectile dysfunction
      significantly improved following the treatment of Saikokaryukotsuboreito 7.5
      g/day. The other case was a 43-year-old man with schizophrenia who was receiving
      fluphenazine decanoate at 50 mg/month and had difficulties in ejaculation; add-on
      of Saikokaryukotsuboreito 7.5 g/day recovered his ejaculatory function. There has
      been no report on the effectiveness of Japanese herbal medicine formulations for
      antipsychotic-induced sexual dysfunction. Although the effectiveness of
      Saikokaryukotsuboreito needs to be tested in systematic clinical trials, this
      herbal medicine may be a treatment option to consider for this annoying side
      effect. 

PMID- 24587935
TI  - Ultrasound of primary aneurysmal bone cyst.
AB  - Aneurysmal bone cysts (ABC) are rare, benign, expansile lesions of bone often
      found in the metaphyses of long bones in pediatric and young adult population.
      Multiple fluid levels are typically seen on imaging with magnetic resonance
      imaging (MRI) or computed tomography (CT). We describe a case of a primary ABC in
      the fibula of a 34-year-old man diagnosed on ultrasound with a mobile fluid level
      demonstrated sonographically. 

PMID- 24587936
TI  - Histopathological Changes of the Thyroid and Parathyroid Glands in HIV-Infected
      Patients.
AB  - Objective. To study histopathology of the thyroid and parathyroid glands in HIV
      infected African Americans in the United States. Methods. A retrospective review
      of 102 autopsy cases done by the Department of Pathology at Howard University
      Hospital from 1980 through 2007 was conducted. The histopathological findings of
      the thyroid and parathyroid glands were reviewed, both macroscopically and
      microscopically. A control group of autopsy patients with chronic non-HIV
      diseases was examined. Results. There were 71 males (70%) and 31 females (30%)
      with an average age of 38 years (range: 20-71 y). Thirteen patients with abnormal
      thyroid findings were identified. Interstitial fibrosis was the most common
      histological finding (4.9%), followed by thyroid hyperplasia (1.9%). Infectious
      disease affecting the thyroid gland was limited to 2.9% and consisted of
      mycobacterium tuberculosis, Cryptococcus neoformans, and cytomegalovirus. Kaposi
      sarcoma of the thyroid gland was present in only one case (0.9%). Parathyroid
      hyperplasia was the most common histological change noted in the parathyroid
      glands. Comparing the histological findings of cases and controls, we found a
      similar involvement of the thyroid, with a greater prevalence of parathyroid
      hyperplasia in HIV patients. Conclusion. Thyroid and parathyroid abnormalities
      are uncommon findings in the HIV-infected African American population. 

PMID- 24587937
TI  - Influence of hypertension on neurocognitive domains in nondemented Parkinson's
      disease patients.
AB  - Objective. Health comorbidities, particularly cardiovascular risk factors, are
      well known to pose risks for cognitive decline in older adults. To date, little
      attention has focused on the impact of these comorbidities on Parkinson's disease
      (PD). This study examined the prevalence and contribution of comorbidities on
      cognitive status in PD patients, above and beyond the effects of disease
      severity. Methods. A cross sectional design was used, including
      neuropsychological data on 341 PD patients without severe cognitive decline.
      Comorbidity data were collected via medical chart review. Data were analyzed
      using a series of multiple hierarchical regressions, controlling for PD-related
      disease variables. Results. Overall sample characteristics are 69% male, disease
      duration 9.7 years, Unified Parkinson's Disease Rating Scale 26.4, and age 64.7
      years. Hypercholesterolemia (41.6%), hypertension (38.1%), and hypotension
      (30.2%) were the most reported comorbidities. The presence of hypertension
      significantly contributed to domains of executive function and verbal memory. The
      cooccurrence of orthostatic hypotension moderated the relationship between
      hypertension and executive function. Conclusions. This study on a large cohort of
      PD patients provides evidence for a detrimental influence of health
      comorbidities, particularly hypertension, on cognitive domains that have
      traditionally been conceptualized as being frontally and/or temporally mediated. 

PMID- 24587938
TI  - Effect of Intermittent Positive Pressure Ventilation on Depth of Anaesthesia
      during and after Isoflurane Anaesthesia in Sulphur-Crested Cockatoos (Cacatua
      galerita galerita).
AB  - This study aimed to determine the effect of intermittent positive pressure
      ventilation (IPPV) on the depth of inhalation anaesthesia in parrots. Anaesthesia
      was induced with 3.0% isoflurane in six Sulphur-crested Cockatoos (Cacatua
      galerita galerita) and maintained using either 1.5% or 3.0% during spontaneous
      ventilation (SV) or IPPV at 6 (IPPV-6) or 12 (IPPV-12) breaths per minute. The
      time taken for the appearance of somatic reflexes and the return of SV after IPPV
      was recorded. During recovery, the body jerk, beak, eye, and shivering reflexes
      appeared after 126 +/- 27 s, 133 +/- 26 s, 165 +/- 34 s, and 165 +/- 44 s,
      respectively. All cockatoos developed apnoea after IPPV-12 and only some did
      after IPPV-6. Return of SV after IPPV-12 was delayed compared to IPPV-6. Recovery
      times after the SV runs were significantly different between 1.5% and 3.0%
      isoflurane anaesthesia. Similarly, after IPPV, the recovery times were
      significantly different between 1.5% and 3.0% isoflurane anaesthesia. Recovery
      times after 3.0% inhaled isoflurane were longer than those of 1.5% inhaled
      isoflurane. In conclusion, cockatoos recovering from isoflurane anaesthesia are
      likely to exhibit body jerk, beak, eye, and shivering reflexes in that order.
      IPPV increases the depth of anaesthesia in a rate and dose-related manner and
      prolongs recovery. 

PMID- 24587940
TI  - The effect of different types of physical exercise on the behavioural and
      physiological parameters of standardbred horses housed in single stalls.
AB  - The aim of this study was to investigate the impacts of three different physical
      exercises on the physiological and behavioural patterns of Standardbred trotters
      housed in single stalls. Twelve racing mares were observed twice during each
      different exercise: daily training (DT) consisted of forty minutes at slow trot
      (4-5 m/s) in a small track; maximal exercise (ME) consisted of 1600 m run at
      maximal velocity; race (R) was a real race of 1600 m. The mares were examined at
      rest in their stall (Time I), soon after the completion of the exercise (Time
      II), one hour (Time III), and two hours (Time IV) after the exercise. Their heart
      rate, respiratory rate, and rectal temperature were recorded and they were
      videotaped in order to complete a focal animal sampling ethogram. All
      physiological parameters increased after exercise, in accordance with its
      intensity. After R and ME horses spent more time drinking, eating, and standing.
      The incidence of abnormal behaviours was very low and it was not affected by the
      different types of exercise. Overall, the assessment of horse behaviour after
      physical exercise by means of a focal animal sampling ethogram represents a
      useful tool to monitor equine welfare. 

PMID- 24587939
TI  - Peritoneal response to abdominal surgery: the role of equine abdominal adhesions
      and current prophylactic strategies.
AB  - Intra-abdominal adhesions constitute a significant clinical and surgical problem
      that can lead to complications such as pain and bowel occlusion or subocclusion.
      These adhesions are frustrating and potentially fatal, representing a major
      postoperative complication in abdominal surgery. It is estimated that 32% of
      horses undergoing laparotomy will present clinical symptoms due to adhesions, but
      the true prevalence is not known because a large proportion of animals with
      postoperative recurrent colics are medically treated or submitted to euthanasia
      without necropsy. Adhesions are highly cellular, vascularized, dynamic structures
      that are influenced by complex signaling mechanisms. Understanding their
      pathogenesis could assist in applying better therapeutic strategies and in
      developing more effective antiadhesion products. Currently, there are no
      definitive strategies that prevent adhesion formation, and it is difficult to
      interpret the results of existing studies due to nonstandardization of an
      induction model and evaluation of their severity. The best clinical results have
      been obtained from using minimally traumatic surgical techniques, anti
      inflammatory agents, antimicrobials, anticoagulants, and mechanical separation of
      serosal surfaces by viscous intraperitoneal solutions or physical barriers. This
      paper aims to review adhesion formation pathogenesis, guide the understanding of
      major products and drugs used to inhibit adhesion formation, and address their
      effectiveness in the equine species. 

PMID- 24587941
TI  - Spectrophotometric determination of gemifloxacin mesylate, moxifloxacin
      hydrochloride, and enrofloxacin in pharmaceutical formulations using Acid dyes.
AB  - SIMPLE, RAPID, AND EXTRACTIVE SPECTROPHOTOMETRIC METHODS WERE DEVELOPED FOR THE
      DETERMINATION OF SOME FLUOROQUINOLONES ANTIBIOTICS: gemifloxacin mesylate (GMF),
      moxifloxacin hydrochloride (MXF), and enrofloxacin (ENF) in pure forms and
      pharmaceutical formulations. These methods are based on the formation of ion-pair
      complexes between the basic drugs and acid dyes, namely, bromocresol green (BCG),
      bromocresol purple (BCP), bromophenol blue (BPB), bromothymol blue (BTB), and
      methyl orange (MO) in acidic buffer solutions. The formed complexes were
      extracted with chloroform and measured at 420, 408, 416, 415, and 422 nm for BCG,
      BCP, BPB, BTB, and MO, respectively, for GMF; at 410, 415, 416, and 420 nm for
      BCP, BTB, BPB, and MO, respectively, for MXF; and at 419 and 414 nm for BCG and
      BTB, respectively, in case of ENF. The analytical parameters and their effects
      are investigated. Beer's law was obeyed in the ranges 1.0-30, 1.0-20, and 2.0-24 
      MU g mL(-1) for GMF, MXF, and ENF, respectively. The proposed methods have been
      applied successfully for the analysis of the studied drugs in pure forms and
      pharmaceutical formulations. Statistical comparison of the results with the
      reference methods showed excellent agreement and indicated no significant
      difference in accuracy and precision. 

PMID- 24587942
TI  - Body adiposity index: its relevance and validity in assessing body fatness of
      adults.
AB  - Background. One of the limitations of body mass index is its accuracy to assess
      body fatness. To address this limitation, a new index, body adiposity index, has
      been developed. However its validity needs to ascertained. Objective. Our aim was
      to investigate sex-specific relationship between BAI, BMI, and percent body fat
      in an endogamous population of Delhi, India. Method. Data was collected from 578
      adults on bodyweight, height, skinfold thicknesses, hip circumference, waist
      circumference, and systolic and diastolic blood pressure. Pearson's correlations
      were calculated for BAI and BMI with PBF. Differences in the correlation
      coefficients were examined using Fisher's z tests. Receiver operating
      characteristic analysis was used to compare the predictive validity and to
      determine optimal cut-off values. Odds ratios were calculated to assess the risk
      of having hypertension using the proposed cut-off points. Results. The
      correlations of PBF with BMI (men: r = 0.83; women: r = 0.71) were stronger than
      those with BAI (men: r = 0.66; women: r = 0.58). In men, the sensitivity and
      specificity of BAI to predict hypertension were higher than other anthropometric
      markers but lower than BMI. In women, the sensitivity of BAI was higher than BMI
      and WC. Conclusions. BAI can be used as an additional marker for screening
      population; however its validity needs to be demonstrated on other populations
      too. 

PMID- 24587943
TI  - Downregulation of RelA (p65) by Rapamycin Inhibits Murine Adipocyte
      Differentiation and Reduces Fat Mass of C57BL/6J Mice despite High Fat Diet.
AB  - Rapamycin (RAPA) is a clinical immunosuppressive agent first reported in the
      literature in 1975 after its discovery in a soil sample from the island of Rapa
      Nui. Aside from the well-documented effects of RAPA on cell division and
      immunologic response, the literature reveals it to have negative effects on
      adipocyte and osteocyte differentiation as well. Understanding of the molecular
      effects of RAPA on cell differentiation is fragmentary in regard to these cell
      lineages. In this paper, we examined a potential mechanism for RAPA's effects on
      adipocyte differentiation in vitro and in vivo. The data point to a unique role
      of Rel A (p65)-a component of the NF-kappaB system-in mediating this event. In
      murine adipose derived stem cell cultures (muADSCs) from C57BL/6J mice, RAPA was
      found to selectively downregulate RelA/p65, mammalian target of rapamycin (mTOR),
      and do so in a dose-dependent manner. This implies a novel role for RelA in
      adipocyte biology. Intracellular lipid accumulation-as subjectively observed-was
      also decreased in muADSCs treated with RAPA. Mice treated with RAPA had reduced
      overall body weight and reduced size of both intraabdominal and subcutaneous fat
      pads. When treated with RAPA, mice fed a high fat diet did not develop obesity
      and were not different from their regular diet controls in terms of body weight.
      These results suggested that RAPA inhibits adipogenesis and lipogenesis of
      muADSCs resulting in a prevention of obesity in C57BL/6J mice. This inhibition is
      strong enough to negate the effects of a high fat diet and seems to act by
      downregulating the RelA/p65 mTOR signaling pathway-a key component of the NF
      kappaB family. 

PMID- 24587944
TI  - The usefulness of component-resolved diagnostics in food allergy.

PMID- 24587945
TI  - Prevalence of allergic rhinitis in china.
AB  - Allergic rhinitis (AR) is a serious systemic allergic disease, which together
      with comorbid asthma causes major illness and disability worldwide. Recent
      epidemiological studies have revealed wide variations in the increasing
      prevalence of AR and allergies globally, including in China. Despite a markedly
      higher population than western countries, and a landmass close to Europe in area,
      little epidemiological data is available on AR in China. Thus, the present study
      reviewed the prevalence, comorbid allergic diseases, trends and pattern of
      sensitizing allergens in adults and children suffering from AR in China.
      Available data indicated that despite variations in the prevalence of AR in
      different regions of the country, the prevalence of AR has increased in both
      adults and children over the last 2 decades. Similarly, there has been an
      increase in a "western"-type lifestyle, industrialization and air pollution over
      this period, which may have contributed to the increased prevalence of AR
      observed in China. 

PMID- 24587946
TI  - Integrating evidence for managing asthma in patients who smoke.
AB  - Cigarette smoking among asthma patients is associated with worsening symptoms and
      accelerated decline in lung function. Smoking asthma is also characterized by
      increased levels of neutrophils and macrophages, and greater small airway
      remodeling, resulting in increased airflow obstruction and impaired response to
      corticosteroid therapy. As a result, smokers are typically excluded from asthma
      randomized controlled trials (RCTs). The strict inclusion/exclusion criteria used
      by asthma RCTs limits the extent to which their findings can be extrapolated to
      the routine care asthma population and to reflect the likely effectiveness of
      therapies in subgroups of particular clinical interest, such as smoking
      asthmatics. The inclusion of smokers in observational asthma studies and
      pragmatic trials in asthma provides a way of assessing the relative effectiveness
      of different treatment options for the management of this interesting clinical
      subgroup. Exploratory studies of possible treatment options for smoking asthma
      suggest potential utility in: prescribing higher-dose ICS; targeting the small
      airways of the lungs with extra-fine particle ICS formulations; targeting
      leukotreines, and possibly also combinations of these options. However, further
      studies are required. With the paucity of RCT data available, complementary
      streams of evidence (those from RCTs, pragmatic trials and observational studies)
      need to be combined to help guide judicious prescribing decisions in smokers with
      asthma. 

PMID- 24587947
TI  - Usefulness of nBos d 4, 5 and nBos d 8 Specific IgE Antibodies in Cow's Milk
      Allergic Children.
AB  - PURPOSE: The aim of study was to assess the value of recombinants in predicting
      the degree of symptoms in children with and without anaphylaxis to cow's milk.
      METHODS: The study included 79 children (70+/-40 months) referred to the
      Allergological Unit of the Pediatric Department between the years 2008-2012.
      Group A was composed of 17 children (78+/-49.6 months) with anaphylaxis after
      ingestion of milk. Group B was composed of 62 children (73.1+/-38.6 months)
      without a history of anaphylaxis, but with less severe symptoms (gastrointestinal
      and/or skin symptoms). All patients from Group B had a positive open challenge
      with cow's milk. All patients underwent an allergic evaluation and blood samples
      were collected to test for IgE to recombinans of milk (nBos d 4, 5, 8). RESULTS:
      A significant difference in nBos d 8 emerged with higher levels in Group A
      (median [IQR]=2.80 [0.91-16.1]) than B (0.65 [0.24-1.67]; P=0.006), whereas there
      were no statistically significant differences for nBos d 4 and 5. The
      recombinants' sum was higher in Group A than B: 8.39 [2.72-41.39] vs 3.04 [1.85
      7.31] kUA/L; P=0.044. The recombinant nBos d 8 was superior to the other
      recombinants in identifying children at risk for anaphylaxis, with an area under
      the curve of 0.718 (95% CI, 0.57-0.86, P=0.006). Considering a cutoff of 1.8
      kUA/L, nBos d 8 had the most favorable sensitivity and specificity ratio
      (sensitivity=0.65, specificity=0.77) with an odd ratio of 6.02 (95% C.I: 1.89
      19.23). CONCLUSIONS: This study suggested 2 phenotypes of allergic children,
      "high-anaphylaxis-risk" and "milder-risk". These types can be differentiated
      through measuring the level of IgE to nBos d 8.

PMID- 24587948
TI  - The effects of inhaled albuterol in transient tachypnea of the newborn.
AB  - PURPOSE: Transient tachypnea of the newborn (TTN) is a disorder caused by the
      delayed clearance of fetal alveolar fluid. beta-adrenergic agonists such as
      albuterol (salbutamol) are known to catalyze lung fluid absorption. This study
      examined whether inhalational salbutamol therapy could improve clinical symptoms
      in TTN. Additional endpoints included the diagnostic and therapeutic efficacy of
      salbutamol as well as its overall safety. METHODS: From January 2010 through
      December 2010, we conducted a prospective study of 40 newborns hospitalized with
      TTN in the neonatal intensive care unit. Patients were given either inhalational
      salbutamol (28 patients) or placebo (12 patients), and clinical indices were
      compared. RESULTS: The duration of tachypnea was shorter in patients receiving
      inhalational salbutamol therapy, although this difference was not statistically
      significant. The duration of supplemental oxygen therapy and the duration of
      empiric antibiotic treatment were significantly shorter in the salbutamol-treated
      group. No adverse effects were observed in either treatment group. CONCLUSIONS:
      Inhalational salbutamol therapy reduced the duration of supplemental oxygen
      therapy and the duration of empiric antibiotic treatment, with no adverse
      effects. However, the time between salbutamol therapy and clinical improvement
      was too long to allow definitive conclusions to be drawn. Further studies
      examining a larger number of patients with strict control over dosage and
      frequency of salbutamol inhalations are necessary to better direct the treatment
      of TTN.

PMID- 24587949
TI  - Prevalence of immediate-type food allergy in early childhood in seoul.
AB  - PURPOSE: There are scanty epidemiologic data on the prevalence of food allergy
      (FA) among preschool children in Asia. We performed this study to determine the
      prevalence and causative foods of immediate-type FA in early childhood in Korea.
      METHODS: A questionnaire-based, cross-sectional study was performed between
      September and October 2011. Children aged 0-6 years were recruited from 301
      public child care centers in Seoul. Parents were asked to complete a
      questionnaire on FA. Children with FA were classified into "perceived FA, ever,"
      "immediate-type FA, ever," and "immediate-type FA, current" according to the
      algorithm. RESULTS: A total of 16,749 children were included in this study. The
      prevalence of "perceived FA, ever," "immediate-type FA, ever," and "immediate
      type FA, current" was 15.1%, 7.0%, and 3.7%, respectively. "Immediate-type FA,
      current" was reported by 182 (4.9%) out of 3,738 children aged <=2 years, 262
      (3.4%) of 7,648 children aged 3-4 years, and 177 (3.3%) of 5,363 children aged 5
      6 years. Hen's egg (126/621) was the most frequent cause as the individual food
      item, followed by cow's milk (82/621) and peanut (58/621). Among the food groups,
      fruits (114/621), tree nuts (90/621) and crustaceans (85/621) were the most
      common offending foods. The three leading causes of food-induced anaphylaxis were
      hen's egg (22/47), cow's milk (15/47), and peanut (14/47). CONCLUSIONS: The
      prevalence of immediate-type FA in early childhood is 3.7%, and is higher in
      younger children. The most common offending foods differed with age.

PMID- 24587950
TI  - The Interaction Between Allelic Variants of CD86 and CD40LG: A Common Risk Factor
      of Allergic Asthma and Rheumatoid Arthritis.
AB  - PURPOSE: Allergic asthma (AA) and rheumatoid arthritis (RA) are immune tolerance
      related diseases, and immune tolerance is known to be influenced by costimulatory
      molecules. In this study, we sought to identify common genetic susceptibility in
      AA and RA. METHODS: Two hundred cases of AA, 184 cases of RA, and 182 healthy
      controls were recruited at the Seoul National University Hospital, Seoul, Korea.
      Eight single nucleotide polymorphisms (SNPs) in five genes coding costimulatory
      molecules, namely, -318C>T, +49A>G, and 6230G>A in CTLA4, IVS3+17T>C in CD28, 
      3479T>G and I179V in CD86, -1C>T in CD40, and -3458A>G in CD40LG were scored, and
      genetic interactions were evaluated by multifactor dimensionality reduction (MDR)
      analysis. RESULTS: MDR analysis revealed a significant gene-gene interaction
      between -3479T>G CD86 and -3458A>G CD40LG for AA. Subjects with the T/T genotype
      of -3479T>G CD86 and the A/A genotype of -3458A>G CD40LG were found to be
      significantly more likely to develop AA than those with the T/T genotype of 
      3479T>G CD86 and A/- genotype of -3458A>G CD40LG (adjusted OR, 6.09; 95% CI, 2.89
      12.98; logistic regression analysis controlled by age). Similarly those subjects
      showed a significant risk of developing RA (adjusted OR, 39.35; 95% CI, 15.01
      107.00, logistic regression analysis controlled by age). CONCLUSIONS: Our
      findings suggest that a genetic interaction between CD86 and CD40LG favors the
      development of both AA and RA.

PMID- 24587951
TI  - Polymorphisms of ATF6B Are Potentially Associated With FEV1 Decline by Aspirin
      Provocation in Asthmatics.
AB  - PURPOSE: Endoplasmic reticulum (ER) stress has recently been observed to activate
      NF-kappaB and induce inflammatory responses such as asthma. Activating
      transcription factor 6beta (ATF6B) is known to regulate ATFalpha-mediated ER
      stress response. The aim of this study is to investigate the associations of
      ATF6B genetic variants with aspirin-exacerbated respiratory disease (AERD) and
      its major phenotype, % decline of FEV1 by aspirin provocation. METHODS: Four
      common single nucleotide polymorphisms (SNPs) of ATF6B were genotyped and
      statistically analyzed in 93 AERD patients and 96 aspirin-tolerant asthma (ATA)
      as controls. RESULTS: Logistic analysis revealed that 2 SNPs (rs2228628 and
      rs8111, P=0.008; corrected P=0.03) and 1 haplotype (ATF6B-ht4, P=0.005; corrected
      P=0.02) were significantly associated with % decline of FEV1 by aspirin
      provocation, whereas ATF6B polymorphisms and haplotypes were not associated with
      the risk of AERD. CONCLUSIONS: Although further functional and replication
      studies are needed, our preliminary findings suggest that ATF6B may be related to
      obstructive phenotypes in response to aspirin exposure in adult asthmatics.

PMID- 24587952
TI  - Effects of fungi and eosinophils on mucin gene expression in rhinovirus-infected
      nasal epithelial cells.
AB  - PURPOSE: Fungi, rhinoviruses (RVs), and eosinophils are associated with upper
      respiratory diseases. We evaluated the effects of fungal stimulation and
      eosinophil co-culture on the expression of mucin genes in RV-infected nasal polyp
      epithelial cells. METHODS: Nasal polyp epithelial cells were obtained from
      chronic rhinosinusitis patients. Cultured epithelial cells were stimulated with
      Alternaria and Aspergillus with or without RV-16 infection. The epithelial cells
      were co-cultured with eosinophils for 16 h. MUC4, MUC5AC, MUC5B, and MUC8 mRNA
      expressions in the epithelial cells were quantified using real-time RT-PCR. To
      determine the underlying mechanism, nuclear factor-kappaB (NF-kappaB), activator
      protein-1 (AP-1), and mitogen-activated protein kinase (MAPK) inhibitors were
      used to inhibit mucin gene expression. RESULTS: Fungi and RV-16 induced mucin
      gene expression in nasal polyp epithelial cells. However, there was no
      synergistic increase in mucin gene expression, with the exception of MUC4 mRNA
      expression stimulated by 25 ug/mL Aspergillus. When RV-16-infected epithelial
      cells were stimulated with fungi and then co-cultured with eosinophils, MUC4,
      MUC5B, and MUC8 mRNA expressions increased. Mucin gene expression was inhibited
      by NF-kappaB inhibitors. CONCLUSIONS: RV-16, airborne fungi, and eosinophils may
      exacerbate the inflammatory process in nasal mucosal diseases by enhancing mucin
      gene expression.

PMID- 24587953
TI  - Cross-reactivity to Acetaminophen and Celecoxib According to the Type of
      Nonsteroidal Anti-inflammatory Drug Hypersensitivity.
AB  - PURPOSE: Identification of tolerable alternative analgesics is crucial for
      management in nonsteroidal anti-inflammatory drug (NSAID)-sensitive patients. We
      investigated cross-reactivity of acetaminophen and celecoxib according to the
      type of aspirin/NSAID hypersensitivity and aimed to determine the risk factors
      for cross-intolerance. METHODS: We retrospectively reviewed the medical records
      of patients intolerant to aspirin and NSAIDs who had undergone an acetaminophen
      and/or celecoxib oral provocation test. Aspirin/NSAID hypersensitivity was
      classified into 4 types according to a recently proposed classification: aspirin
      exacerbated respiratory disease (AERD), aspirin-exacerbated chronic urticaria
      (AECU), aspirin-induced acute urticaria/angioedema (AIAU), and NSAID-induced
      blended reaction (NIRD). RESULTS: A total of 180 patients with hypersensitivity
      to aspirin and NSAIDs were enrolled; 149 acetaminophen provocation test results
      and 145 celecoxib provocation test results were analyzed. The overall cross
      reaction rates to acetaminophen and celecoxib were 24.8% and 10.3%, respectively.
      There was a significant difference in the cross-reactivity to acetaminophen
      according to the type of NSAID hypersensitivity. Cross-reactivity to
      acetaminophen was highest in the AECU group (43.9%), followed by the AERD
      (33.3%), NIBR (16.7%), and AIAU (12.5%) groups. Underlying chronic urticaria was
      more prevalent in patients with cross-intolerance to both acetaminophen (P=0.001)
      and celecoxib (P=0.033). Intolerance to acetaminophen was associated with
      intolerance to celecoxib (P<0.001). CONCLUSIONS: Acetaminophen and celecoxib may
      induce adverse reactions in a non-negligible portion of aspirin/NSAID-sensitive
      patients. Physicians should be aware of the possible cross-reactions of these
      alternative drugs and consider an oral challenge test to confirm their
      tolerability.

PMID- 24587954
TI  - Receptor Interacting Protein 2 (RIP2) Is Dispensable for OVA-Induced Airway
      Inflammation in Mice.
AB  - PURPOSE: Asthma is a pulmonary chronic inflammatory disease characterized by
      airway obstruction and hyperresponsiveness. Pattern recognition receptors are
      known to play a key role in the development of allergic diseases as well as host
      defenses against microbial infection. Receptor interacting protein 2 (RIP2), a
      serine/threonine kinase, is an adaptor molecule of NOD1 and NOD2, and genetic
      variation in this receptor is known to be associated with the severity of
      allergic asthma in children. In this study, we examined the role of RIP2 in the
      development of allergic airway inflammation in a mouse model. METHODS: Airway
      inflammation was induced in mice through intranasal administration of ovalbumin
      (OVA) after 2 intraperitoneal immunizations with OVA. Lung inflammation and mucus
      hypersecretion were examined histologically and total cell infiltration in
      bronchoalveolar (BAL) fluids was determined. Levels of the Th2-related cytokines,
      IL-5 and IL-13, in lung extracts were measured by ELISA. Serum antigen-specific
      IgE and IgG1 levels were also assessed. RESULTS: OVA-induced lung inflammation
      and mucus hypersecretion were not different between WT and RIP2-deficient mice.
      The IL-5 and IL-13 levels in the bronchoalveolar (BAL) fluids were also not
      impaired in RIP2-deficient mice compared to WT mice. Moreover, RIP2 deficiency
      did not affect serum OVA-specific IgG1 and IgE levels. CONCLUSIONS: Our results
      suggest that RIP2 is not associated with the development of allergic airway
      inflammation.

PMID- 24587955
TI  - Reference values and determinants of fractional concentration of exhaled nitric
      oxide in healthy children.
AB  - PURPOSE: Measurement of the fractional concentration of exhaled nitric oxide
      (FeNO) is a quantitative, noninvasive, simple, safe method of assessing airway
      inflammation. While FeNO measurement has been standardized, reference values for
      elementary school children are scarce. The aim of this study was to establish
      reference values for FeNO in children. METHODS: FeNO was measured in elementary
      school children at 6-12 years of age in Seoul, Korea, following American Thoracic
      Society guidelines and using a chemiluminescence analyzer (NIOX Exhaled Nitric
      Oxide Monitoring System, Aerocrine, Sweden). A total of 1,252 children completed
      a modified International Study of Asthma and Allergy in Children (ISAAC)
      questionnaire; FeNO was measured in 1,063 children according to the protocol and
      in 808 children defined as healthy controls. RESULTS: Mean FeNO were 10.32 ppb,
      16.58 ppb, and 12.36 ppb in non-atopic, atopic, and all 808 healthy controls,
      respectively. FeNO was not associated with age and gender. The FeNO reference
      equations were determined by multiple linear regression analysis, taking into
      account the variables of age, height, weight, total IgE, eosinophil percent, and
      bronchial hyper-responsiveness (methacholine PC20). FeNO=0.776+0.003*total
      IgE+0.340*eosinophil percent; coefficient of determination (R2)=0.084 in the 501
      healthy non-atopic controls. FeNO=-18.365+1.536*eosinophil percent, R2=0.183 in
      the 307 healthy atopic controls; and FeNO=-7.888+0.130*Height+0.004*total
      IgE+1.233*eosinophil percent, R2=0.209 in the 808 all healthy controls.
      Eosinophil percent was correlated with FeNO in all healthy controls. FeNO was not
      associated with BMI. CONCLUSION: This study provides reference values for FeNO
      that can be used to evaluate airway inflammation in elementary school children.
      Determinants that could most accurately predict FeNO in healthy school-age
      children were assessed.

PMID- 24587956
TI  - Potential masking of airway eosinophilic inflammation by combination therapy in
      asthma.
AB  - PURPOSE: Long-acting beta2 agonists (LABA) may mask ongoing bronchial
      inflammation, leaving asthmatic patients at greater risk of severe complications.
      The aim of this study was to compare the effect of combination therapy using low
      dose inhaled corticosteroids (ICS) plus LABA on airway inflammation in asthma to
      the effect of medium-dose ICS alone. METHODS: Twenty-four patients with asthma
      not controlled by low-dose (400 ug per day) budesonide alone were enrolled in
      this prospective crossover study. Patients were randomized into 2 treatment
      phases: one receiving medium-dose (800 ug per day) budesonide (ICS phase), and
      the other receiving a combination therapy of low-dose budesonide/formoterol (360
      ug/9 ug per day) delivered by a single inhaler (LABA phase). Each treatment phase
      lasted for 6 week, after which patients were crossed over. Asthma symptoms, lung
      function, and airway inflammation were compared between the 2 phases. RESULTS:
      Twenty-three patients completed the study; adequate sputum samples were collected
      from 17 patients. Asthma symptoms and lung function remained similar between the
      2 phases. However, the mean sputum eosinophil percentage was higher in the LABA
      phase than in the ICS phase (5.07+/-3.82% vs. 1.02+/-1.70%; P<0.01). Sputum
      eosinophilia (>=3%) was more frequently observed in the LABA phase than in the
      ICS phase (six vs. two). CONCLUSION: Addition of LABA may mask airway
      eosinophilic inflammation in asthmatic patients whose symptoms are not controlled
      with low-dose ICS.

PMID- 24587957
TI  - A case of eosinophilic fasciitis presenting as pitting edema of the lower
      extremities.
AB  - Eosinophilic fasciitis is a rare disease characterized by diffuse fasciitis with
      peripheral eosinophilia and progressive induration and thickening of the skin and
      soft tissues. We report a 19-year-old female who presented with pitting edema in
      both lower extremities. She had a history of excessive physical activity before
      her symptoms developed. Physical examination revealed 2+ pitting edema in both
      lower legs. She complained of mild pain in both knee joints and feet, with no
      tenderness or heating sensations. Laboratory results were unremarkable except for
      severe eosinophilia. Parasite infection, venous thrombosis, and cardiac and renal
      problems were excluded. A magnetic resonance imaging study of both lower
      extremities revealed increased signal intensity in the subcutaneous lesions,
      consistent with superficial inflammation of the fascia. Mixed perivenular
      lymphoplasmacytic and eosinophilic infiltration in the subcutaneous lesion were
      observed on biopsy. The patient was treated with corticosteroids, resulting in
      remarkable improvement in both edema and eosinophilia. 

PMID- 24587958
TI  - A case of serum sickness-like reaction and anaphylaxis - induced simultaneously
      by rifampin.
AB  - Rifampin is commonly used as a first-line anti-tuberculosis drug, but it can
      induce a serum sickness-like reaction or anaphylaxis. However, it is possible for
      1 drug antigen to induce 2 or more simultaneous immunologic reactions. Here, we
      report a case of a serum-sickness-like reaction and anaphylaxis induced
      concurrently by rifampin. A 25-year-old male presented with high fever and a
      maculopapular rash with vesicles on the hands, which developed 2 weeks following
      regular administration of anti-tuberculosis drugs for tuberculous meningitis,
      including rifampin. Elevated liver enzymes, peripheral neuropathy, and decreased
      serum C3 and C4 levels were found. Interestingly, these symptoms were accompanied
      by severe hypotension. A serum-sickness-like reaction was considered after
      excluding other potential causes for the fever. A drug provocation test showed
      that the fever developed after oral administration of rifampin, suggesting that
      rifampin was the cause of the allergic reaction. However, hypotension, epigastric
      discomfort, and diarrhea also accompanied these symptoms, indicating that IgE
      mediated type I hypersensitivity could be part of the serum sickness-like
      reaction. An intradermal skin test clearly showed an immediate positive reaction
      to rifampin. This case was diagnosed as concurrent serum-sickness-like reaction
      and anaphylaxis induced by rifampin. One drug may therefore induce combined
      allergic reactions via 2 or more simultaneous hypersensitivity responses. 

PMID- 24587959
TI  - Tricarballylic ester formation during biosynthesis of fumonisin mycotoxins in
      Fusarium verticillioides.
AB  - Fumonisins are agriculturally important mycotoxins produced by the maize pathogen
      Fusarium verticillioides. The chemical structure of fumonisins contains two
      tricarballylic esters, which are rare structural moieties and important for
      toxicity. The mechanism for the tricarballylic ester formation is not well
      understood. FUM7 gene of F. verticillioides was predicted to encode a
      dehydrogenase/reductase, and when it was deleted, the mutant produced
      tetradehydro fumonisins (DH4-FB). MS and NMR analysis of DH4-FB1 indicated that
      the esters consist of aconitate with a 3'-alkene function, rather than a 2'
      alkene function. Interestingly, the purified DH4-FB1 eventually yielded three
      chromatographic peaks in HPLC. However, MS revealed that the metabolites of the
      three peaks all had the same mass as the initial single-peak DH4-FB1. The results
      suggest that DH4-FB1 can undergo spontaneous isomerization, probably including
      both cis-trans stereoisomerization and 3'- to 2'-ene regioisomerization. In
      addition, when FUM7 was expressed in Escherichia coli and the resulting enzyme,
      Fum7p, was incubated with DH4-FB, no fumonisin with typical tricarballylic esters
      was formed. Instead, new fumonisin analogs that probably contained isocitrate
      and/or oxalosuccinate esters were formed, which reveals new insight into
      fumonisin biosynthesis. Together, the data provided both genetic and biochemical
      evidence for the mechanism of tricarballylic ester formation in fumonisin
      biosynthesis.

PMID- 24587961
TI  - New records of Cantharellus species from the northwestern Himalayas of India.
AB  - This study investigated several collections of the genus Cantharellus
      (Cantharellaceae) from the northwestern Himalayas, India, on the basis of
      morphology and molecular data. Phylogenetic relationships and species limits were
      investigated by using nuclear ribosomal large subunit sequences (LSU). We
      recognized 13 species: Cantharellus appalachiensis Petersen, C. cibarius Fries,
      C. lateritius (Berk) Singer, C. miniatescens Heinem, C. minor Peck, C.
      pseudoformosus and seven species, C. applanatus sp. nov., C. elongatipes sp.
      nov., C. fibrillosus sp. nov., C. himalayensis sp. nov., C. indicus sp. nov., C.
      natarajanii sp. nov., and C. umbonatus sp. nov., as new to science. All these
      species are described and their taxonomy and ecology are discussed. In addition,
      a key is provided to all the recognized species. The phylogenetic analysis
      recovered 10 major supported clades of Cantharellus species.

PMID- 24587960
TI  - Muscodor kashayum sp. nov. - a new volatile anti-microbial producing endophytic
      fungus.
AB  - Muscodor kashayum (MycoBank no.: MB 803800; GenBank no.: KC481680) is a newly
      described endophytic fungus of a medicinal plant Aegle marmelos (Bael tree),
      growing in the tropical conserved rainforest in the Western Ghats of India.
      Muscodor kashayum possesses distinct morphological, molecular and physiological
      features from the earlier reported Muscodor species. The fungus forms
      characteristic rings of the ropy mycelium on potato dextrose agar medium. This
      sterile fungus is characterised by the presence of a pungent smell which is
      attributable to a blend of more than 23 volatile organic constituents,
      predominantly 3-cyclohexen-1-ol,1-(1,5-dimethyl-4-hexenyl)-4-methyl; 1,6
      dioxacyclododecane-7,12-dione; 2,6-bis(1,1-dimethylethyl)-4-(1-oxopropyl) phenol;
      2,4-di-tert-butylthiophenol and 4-octadecylmorpholine. In the in vitro anti
      microbial assay using M. kashayum, growth of 75% of test fungi/yeasts and 72% of
      the test bacteria were completely inhibited. Therefore, M. Kashayum holds
      potential for future application to be used as a myco-fumigation agent.

PMID- 24587962
TI  - Brave New Love: The Threat of High-Tech "Conversion" Therapy and the Bio
      Oppression of Sexual Minorities.
AB  - Our understanding of the neurochemical bases of human love and attachment, as
      well as of the genetic, epigenetic, hormonal, and experiential factors that
      conspire to shape an individual's sexual orientation, is increasing
      exponentially. This research raises the vexing possibility that we may one day be
      equipped to modify such variables directly, allowing for the creation of "high
      tech" conversion therapies or other suspect interventions. In this article, we
      discuss the ethics surrounding such a possibility, and call for the development
      of legal and procedural safeguards for protecting vulnerable children from the
      application of such technology. We also consider the more difficult case of
      voluntary, adult "conversion" and argue that in rare cases, such attempts might
      be permissible under strict conditions.

PMID- 24587963
TI  - Thinking Ahead on Deep Brain Stimulation: An Analysis of the Ethical Implications
      of a Developing Technology.
AB  - Deep brain stimulation (DBS) is a developing technology. New generations of DBS
      technology are already in the pipeline, yet this particular fact has been largely
      ignored among ethicists interested in DBS. Focusing only on ethical concerns
      raised by the current DBS technology is, albeit necessary, not sufficient. Since
      current bioethical concerns raised by a specific technology could be quite
      different from the concerns it will raise a couple of years ahead, an ethical
      analysis should be sensitive to such alterations, or it could end up with results
      that soon become dated. The goal of this analysis is to address these changing
      bioethical concerns, to think ahead on upcoming and future DBS concerns both in
      terms of a changing technology and changing moral attitudes. By employing the
      distinction between inherent and noninherent bioethical concerns we identify and
      make explicit the particular limits and potentials for change within each
      category, respectively, including how present and upcoming bioethical concerns
      regarding DBS emerge and become obsolete. Many of the currently identified
      ethical problems with DBS, such as stimulation-induced mania, are a result of
      suboptimal technology. These challenges could be addressed by technical advances,
      while for instance perceptions of an altered body image caused by the mere
      awareness of having an implant may not. Other concerns will not emerge until the
      technology has become sophisticated enough for new uses to be realized, such as
      concerns on DBS for enhancement purposes. As a part of the present analysis,
      concerns regarding authenticity are used as an example.

PMID- 24587964
TI  - Catalytic Radical Domino Reactions in Organic Synthesis.
AB  - Catalytic radical-based domino reactions represent important advances in
      synthetic organic chemistry. Their development benefits synthesis by providing
      atom- and step-economical methods to complex molecules. Intricate combinations of
      radical, cationic, anionic, oxidative/reductive, and transition metal mechanistic
      steps result in cyclizations, additions, fragmentations, ring-expansions, and
      rearrangements. This Perspective summarizes recent developments in the field of
      catalytic domino processes.

PMID- 24587965
TI  - A Review of Magnetic Resonance Spectroscopy Studies in Marijuana using
      Adolescents and Adults.
AB  - Marijuana (MJ) remains the most widely used illicit drug of abuse, and
      accordingly, is associated with adverse effects on mental and physical health,
      and neurocognitive decline. Studies investigating the neurobiology of underlying
      MJ effects have demonstrated structural and functional alterations in brain areas
      that contain moderate to high concentrations of cannabinoid (CB1) receptors and
      that are implicated in MJ-related cognitive decrements. Proton magnetic resonance
      spectroscopy (1H MRS), a non-invasive imaging technique used to assess
      neurochemistry, has been widely applied to probe a variety of substance-abusing
      populations. To date, however, there is a relative paucity of MRS published
      studies characterizing changes in neurometabolite concentrations in MJ users.
      Thus, the current review provides a summary of data from the eight existing MRS
      studies of MJ use in adolescents and adults, as well as interpretations and
      implications of study findings. Future MRS studies that address additional
      factors such as sex differences, onset and duration of use, abstinence and age,
      are warranted, and would lead to a more thorough characterization of potential
      neurochemical correlates of chronic MJ use, which would fill critical gaps in the
      existing literature.

PMID- 24587966
TI  - Astrocyte Dysfunctions and HIV-1 Neurotoxicity.
AB  - Astrocytes play an important role in maintaining an optically suited milieu for
      neuronal functionality, and are involved in the progression and outcome of many
      neuropathological conditions. It becomes increasingly evident that astrocytes are
      significant contributors to HIV-1 associated neurological disorders by modulating
      the microenvironment in the central nervous system and releasing proinflammatory
      cytokines. Recent studies have revealed direct metabolic interactions between
      neurons and astrocytes observed particularly in HIV-1-associated neurological
      disorders by which astrocytic dysfunctions disregulate extracellular K+
      homeostasis, intracellular calcium concentration, glutamate clearance, and blood
      brain barrier integrity and permeability. Such dysfunctions are amplified via gap
      junctions, directly or indirectly impacting surrounding neurons and significantly
      contributing to the pathogenesis of HIV-1-associated neuropathology. In this
      review, we tentatively address recent progresses on the roles astrocytes may play
      in HIV-1-associated neurotoxicity.

PMID- 24587968
TI  - Treatment of essential tremor with long-chain alcohols: still experimental or
      ready for prime time?
AB  - AIM: To review current literature on long-chain alcohols and their derivatives as
      novel pharmacotherapy for the treatment of essential tremor (ET). BACKGROUND:
      Currently available and recommended pharmacotherapies for ET are often limited by
      suboptimal treatment effects, frequent adverse effects, and drug interactions.
      While ethanol is reported to profoundly decrease tremor severity in the majority
      of patients with ET, preclinical experience suggests that long-chain alcohols
      such as 1-octanol might lead to a comparable tremor reduction without ethanol's
      typical side effects of sedation and intoxication. Here, we review the literature
      on the first clinical trials on 1-octanol and its metabolite octanoic acid (OA)
      for the treatment of ET. METHODS: The literature on preclinical and clinical
      trials on long-chain alcohols as well as OA was reviewed and summarized, and an
      outlook given on next phases of development. DISCUSSION: 1-octanol was
      demonstrated to be safe and effective in a double-blind, placebo-controlled low
      dose trial, and open-label data showed excellent tolerability and dose-dependent
      efficacy up to 128 mg/kg. Despite 1-octanol's efficacy, its future viability as
      an effective therapy is limited by its pharmacological properties that require
      large volumes to be orally administered. Pharmacokinetic data indicate that OA is
      the active metabolite of 1-octanol. Preclinical efficacy data for OA are
      positive, and human pilot data demonstrated excellent safety as well as efficacy
      in secondary outcome measures of tremor amplitudes. OA also has more favorable
      pharmacological properties for drug delivery; hence, OA may be worth developing
      as a pharmaceutical.

PMID- 24587967
TI  - Eradication of Human Ovarian Cancer Cells by Transgenic Expression of Recombinant
      DNASE1, DNASE1L3, DNASE2, and DFFB Controlled by EGFR Promoter: Novel Strategy
      for Targeted Therapy of Cancer.
AB  - INTRODUCTION: Ovarian cancer is the most deadly among all gynecological cancers.
      Patients undergoing systemic therapies of advanced ovarian cancers suffer from
      horrendous side effects. Cancer survivors and their offspring suffer from
      iatrogenic consequences of systemic therapies: genetic mutations. The ultimate
      goal of our work is development of therapies, which selectively and completely
      eliminate cancer cells, but do not harm healthy cells. An important consideration
      for attaining this goal is the fact that ovarian cancer cells over-express EGFR
      or its mutants, what becomes the factor discriminating them from healthy cells -
      a potential facilitator of personalized therapy. SPECIFIC AIM: The specific aim
      of this project was threefold: (1) to bioengineer suicide genes' carrying vectors
      guided by synthetic antibodies for EGFRvIII and EGFR; (2) to genetically engineer
      DNA constructs for the human, recombinant DNASE1, DNASE1L3, DNASE2, and DFFB
      controlled by the EGFR promoter; (3) to selectively eradicate ovarian cancer
      cells by intranuclear targeting of the transgenically expressed recombinant
      DNases. METHODS: Synthetic antibodies for EGFR and EGFRvIII were selected from
      the human library and used to bioengineer biotag-guided transgenes' vectors.
      Coding sequences for the human DNASE1, DNASE1L3, DNASE2, DFFB controlled by the
      EGFR promoter were amplified from the human cDNA and genetically engineered into
      the plasmid constructs also coding for the fusions with NLS and GFP. The vectors
      carrying transgenes for the DNases were delivered in vitro into human ovarian
      cancer cells from ascites and cultures. RESULTS: Synthetic antibody guided
      vectors delivered the transgenes for the recombinant DNases efficiently into the
      ovarian cancer cells. Transgenic expression and nuclear targeting of the DNases
      in those cells resulted in destruction of their genomes and led to their death,
      as validated by labeling with the molecular death tags. In healthy cells, which
      did not over-express EGFR, no changes were recorded. CONCLUSION: Targeted
      expression of the recombinant DNASE1, DNASE1L3, DNASE2, DFFB in the ovarian
      cancers in vitro resulted in their complete eradication, but had no effects upon
      the healthy cells. This novel therapeutic strategy has a potential for
      streamlining it into in vivo trials, as personalized, targeted therapy of ovarian
      and other cancers.

PMID- 24587969
TI  - Inter-Rater Agreement in the Clinical Diagnosis of Essential Tremor: Data from
      the NEDICES-2 Pilot Study.
AB  - BACKGROUND: Our aim was to assess the diagnostic agreement among the neurologists
      in the Neurological Disorders in Central Spain 2 (NEDICES-2) study; these
      neurologists were assigning diagnoses of essential tremor (ET) vs. no ET.
      METHODS: Clinical histories and standardized video-taped neurological
      examinations of 26 individuals (11 ET, seven Parkinson's disease, three
      diagnostically unclear, four normal, one with a tremor disorder other than ET)
      were provided to seven consultant neurologists, six neurology residents, and five
      neurology research fellows (18 neurologists total). For each of the 26
      individuals, neurologists were asked to assign a diagnosis of "ET" or "no ET"
      using diagnostic criteria proposed by the Movement Disorders Society (MDS). Inter
      rater agreement was assessed both with percent concordance and non-weighted kappa
      statistics. RESULTS: Overall kappa was 0.61 (substantial agreement), with no
      differences between consultant neurologists (kappa = 0.60), neurology residents
      (kappa = 0.61), and neurology research fellows (kappa = 0.66) in subgroup
      analyses. Subanalyses of agreement only among those 15 subjects with a previous
      diagnosis of ET (11 patients) and those with a previous diagnosis of being normal
      (four individuals) showed an overall kappa of 0.51 (moderate agreement).
      DISCUSSION: In a population-based epidemiological study, substantial agreement
      was demonstrated for the diagnosis of ET among neurologists of different levels
      of expertise. However, agreement was lower than that previously reported using
      the Washington Heights-Inwood Genetic Study of Essential Tremor criteria, and a
      head-to-head comparison is needed to assess which is the tool of choice in
      epidemiological research in ET.

PMID- 24587970
TI  - Rescue GPi-DBS for a Stroke-associated Hemiballism in a Patient with STN-DBS.
AB  - BACKGROUND: Hemiballism/hemichorea commonly occurs as a result of a lesion in the
      subthalamic region. CASE REPORT: A 38-year-old male with Parkinson's disease
      developed intractable hemiballism in his left extremities due to a small lesion
      that was located adjacent to the right deep brain stimulation (DBS) lead, 10
      months after bilateral subthalamic nucleus (STN)-DBS placement. He underwent a
      right globus pallidus internus (GPi)-DBS lead implantation. GPi-DBS
      satisfactorily addressed his hemiballism. DISCUSSION: This case offered a unique
      look at basal ganglia physiology in human hemiballism. GPi-DBS is a reasonable
      therapeutic option for the treatment of medication refractory hemiballism in the
      setting of Parkinson's disease.

PMID- 24587972
TI  - Clinical Impact Upon Wound Healing and Inflammation in Moist, Wet, and Dry
      Environments.
AB  - SIGNIFICANCE: Successful treatment of wounds relies on precise control and
      continuous monitoring of the wound-healing process. Wet or moist treatment of
      wounds has been shown to promote re-epithelialization and result in reduced scar
      formation, as compared to treatment in a dry environment. RECENT ADVANCES: By
      treating wounds in a controlled wet environment, delivery of antimicrobials,
      analgesics, other bioactive molecules such as growth factors, as well as cells
      and micrografts, is allowed. The addition of growth factors or transplantation of
      cells yields the possibility of creating a regenerative wound microenvironment
      that favors healing, as opposed to excessive scar formation. CRITICAL ISSUES:
      Although several manufacturers have conceived products implementing the concept
      of moist wound healing, there remains a lack of commercial translation of wet
      wound-healing principles into clinically available products. This can only be
      mitigated by further research on the topic. FUTURE DIRECTIONS: The strong
      evidence pointing to the favorable healing of wounds in a wet or moist
      environment compared to dry treatment will extend the clinical indications for
      this treatment. Further advances are required to elucidate by which means this
      microenvironment can be optimized to improve the healing outcome.

PMID- 24587973
TI  - Disclosure of the Culprits: Macrophages-Versatile Regulators of Wound Healing.
AB  - SIGNIFICANCE: Macrophages are invariably present and tightly regulate all phases
      of adult wound healing, including inflammation, granulation tissue formation, and
      matrix deposition with the unavoidable outcome of scar formation. In response to
      environmental cues, macrophages mount a "classical" pro-inflammatory M1
      activation as opposed to the "alternative" M2 phenotype, with wound macrophages
      having long been viewed as M2 macrophages. RECENT ADVANCES: Recent studies rather
      point to large temporal and phenotypic variations of wound macrophages subsets.
      Therefore, a functional classification of macrophages according to wound-healing
      phases appears to better meet the in vivo complexity. In an ideal but simplistic
      scenario grossly reflecting normal wound healing, initial tissue injury induces
      inflammatory M1-like macrophages, which, upon engulfment of apoptotic neutrophils
      or in response to other inflammation dampening stimuli, switch toward anti
      inflammatory M2-like macrophages and further toward growth factor-producing pro
      fibrotic M2a-like macrophages. Although not yet documented for skin wounds, a
      subset of metalloproteinase-producing fibrolytic M2c-like macrophages may
      contribute to fibrosis resolution. Recent work identified a diversity of novel
      macrophage phenotypes associated with normal and pathologic wound healing, most
      of them ranging out of the M1/M2 paradigm. Iron-overloaded M1-like macrophages
      represent such a novel phenotypic subset driving the non-healing state of chronic
      venous leg ulcers. CRITICAL ISSUES: Despite growing evidence that macrophage
      dysfunctions are, at least in part, responsible for pathologic wound healing,
      including nonhealing wounds and excessive scar formation, these are hardly
      specifically addressed even by modern therapeutic strategies. FUTURE DIRECTIONS:
      If characterized in sufficient detail, distinct macrophage subsets and their
      impaired functions provide ideal targets for improving wound healing.

PMID- 24587971
TI  - Chemokines and Their Receptors Are Key Players in the Orchestra That Regulates
      Wound Healing.
AB  - SIGNIFICANCE: Normal wound healing progresses through a series of overlapping
      phases, all of which are coordinated and regulated by a variety of molecules,
      including chemokines. Because these regulatory molecules play roles during the
      various stages of healing, alterations in their presence or function can lead to
      dysregulation of the wound-healing process, potentially leading to the
      development of chronic, nonhealing wounds. RECENT ADVANCES: A discovery that
      chemokines participate in a variety of disease conditions has propelled the study
      of these proteins to a level that potentially could lead to new avenues to treat
      disease. Their small size, exposed termini, and the fact that their only
      modifications are two disulfide bonds make them excellent targets for
      manipulation. In addition, because they bind to G-protein-coupled receptors
      (GPCRs), they are highly amenable to pharmacological modulation. CRITICAL ISSUES:
      Chemokines are multifunctional, and in many situations, their functions are
      highly dependent on the microenvironment. Moreover, each specific chemokine can
      bind to several GPCRs to stimulate the function, and both can function as
      monomers, homodimers, heterodimers, and even oligomers. Activation of one
      receptor by any single chemokine can lead to desensitization of other chemokine
      receptors, or even other GPCRs in the same cell, with implications for how these
      proteins or their receptors could be used to manipulate function. FUTURE
      DIRECTIONS: Investment in better understanding of the functions of chemokines and
      their receptors in a local context can reveal new ways for therapeutic
      intervention. Understanding how different chemokines can activate the same
      receptor and vice versa could identify new possibilities for drug development
      based on their heterotypic interactions.

PMID- 24587974
TI  - Stem Cells and Healing: Impact on Inflammation.
AB  - SIGNIFICANCE: The number of patients with nonhealing wounds has rapidly
      accelerated over the past 10 years in both the United States and worldwide. Some
      causative factors at the macro level include an aging population, epidemic
      numbers of obese and diabetic patients, and an increasing number of surgical
      procedures. At the micro level, chronic inflammation is a consistent finding.
      RECENT ADVANCES: A number of treatment modalities are currently used to
      accelerate wound healing, including energy-based modalities, scaffoldings, the
      use of mechano-transduction, cytokines/growth factors, and cell-based therapies.
      The use of stem cell therapy has been hypothesized as a potentially useful
      adjunct for nonhealing wounds. Specifically, mesenchymal stem cells (MSCs) have
      been shown to improve wound healing in several studies. Immune modulating
      properties of MSCs have made them attractive treatment options. CRITICAL ISSUES:
      Current limitations of stem cell therapy include the potentially large number of
      cells required for an effect, complex preparation and delivery methods, and poor
      cell retention in targeted tissues. Comparisons of published in-vitro and
      clinical trials are difficult due to cell preparation techniques, passage number,
      and the impact of the micro-environment on cell behavior. FUTURE DIRECTIONS: MSCs
      may be more useful if they are preactivated with inflammatory cytokines such as
      tumor necrosis factor alpha or interferon gamma. This article will review the
      current literature with regard to the use of stem cells for wound healing. In
      addition the anti-inflammatory effects of MSCs will be discussed along with the
      potential benefits of stem cell preactivation.

PMID- 24587976
TI  - Advanced Basal Cell Carcinoma: Epidemiology and Therapeutic Innovations.
AB  - Advanced basal cell carcinomas are a subset of basal cell carcinomas that can be
      difficult to treat either due to their local invasiveness, proximity to vital
      structures, or metastasis. The incidence of all basal cell carcinoma is
      increasing in the United States, although it is not known whether advanced basal
      cell carcinomas (aBCCs) are also increasing. Recently, highly targeted therapy
      based on knowledge of the basal cell carcinoma pathogenesis has become available
      either commercially or through human clinical trials. These orally available
      drugs inhibit the Hedgehog signaling pathway, and lead to advanced basal cell
      carcinoma shrinkage that can enable preservation of adjacent vital organs. In
      this review, we outline the role of Hedgehog pathway inhibitors as well as other
      treatment modalities such as excision, radiotherapy and more traditional
      chemotherapy in treating advanced basal cell carcinomas. We also highlight
      current gaps in knowledge regarding the use and side effects of this targeted
      therapy.

PMID- 24587975
TI  - The Skin-Resident Immune Network.
AB  - The skin provides an effective physical and biological barrier against
      environmental and pathogenic insults whilst ensuring tolerance against commensal
      microbes. This protection is afforded by the unique anatomy and cellular
      composition of the skin, particularly the vast network of skin-associated immune
      cells. These include the long-appreciated tissue-resident macrophages, dendritic
      cells, and mast cells, as well as the more recently described dermal gammadelta T
      cells and innate lymphoid cells. Collectively, these cells orchestrate the
      defense against a wide range of pathogens and environmental challenges, but also
      perform a number of homeostatic functions. Here, we review recent developments in
      our understanding of the various roles that leukocyte subsets play in cutaneous
      immunobiology, and introduce the newer members of the skin immune system.
      Implications for human disease are discussed.

PMID- 24587977
TI  - Merkel Cell Carcinoma: Epidemiology, Target, and Therapy.
AB  - Merkel cell carcinoma (MCC) is an aggressive neuroendocrine tumor of the skin
      with a rising incidence. MCC has metastatic potential regardless the size of the
      primary tumor and a 5-year disease associated mortality rate is 46 %. Surgery and
      radiation are the mainstays of management for primary MCC. There is no evidence
      based effective chemotherapy for recurrent or metastatic diseases to date. In
      depth mechanistic studies in MCC have uncovered important cellular events and the
      association with a polyomavirus, which has provided direct evidence for molecular
      targeted and immunotherapy. Further perspective studies and clinical trials are
      warranted to provide reliable evidence of possible pitfalls and effectiveness of
      molecular targeted immunotherapy alone or in combination with chemotherapy in
      MCC.

PMID- 24587978
TI  - Paradoxes in Carcinogenesis: There Is Light at the End of That Tunnel!
AB  - The exchange of opinions motivated by Dr. Baker's article "Paradoxes in
      carcinogenesis should spur new avenues of research: An historical perspective"
      illustrates the reasons why the field of cancer research is stuck in a dead end.
      This paralysis presents a rich opportunity for philosophers, historians and
      sociologists of science to decipher the whys of this impasse. On the strictly
      biological front, we suggest to reinstate in cancer research the time proven
      practice so productive in the physical sciences of discarding wrong hypotheses
      and theories. We share the suggestion by Dr. Baker to stop trying to unify the
      two main theories of carcinogenesis, i.e., the Somatic Mutation Theory (SMT) and
      the Tissue Organization Field Theory (TOFT) because they are incompatible. Dr.
      Baker suggests breaching the impasse by investing in paradox-driven research. We
      discuss the barriers to the implementation of this novel strategy, and the
      significant impact that this strategy will have on knowledge at large and its
      application for the prevention and cure of cancer.

PMID- 24587979
TI  - Cancer Stem Cells under Hypoxia as a Chemoresistance Factor in Breast and Brain.
AB  - Over the last fifteen years, basic science and clinical studies have aimed to
      identify cancer stem cells (CSCs) in multiple types of cancer in order to unravel
      their mechanistic roles in cancer recurrence for therapeutic exploitation.
      Exposure of cells and tissues to hypoxia, or sub-atmospheric concentrations of
      oxygen (< 21% O2), stimulates various stress response pathways that bias the
      cells towards a self-preserving, anti-apoptotic phenotype. Despite major advances
      in our understanding of hypoxia, CSCs, and their interrelated nature, some of the
      most promising cancer therapies have shown limited efficacy in clinic for the
      past few years, in part due to the inherently hypoxic nature of growing tumors.
      In the present article, we discuss recent findings regarding the behavior of
      breast and brain CSCs under hypoxia, as well as the mechanisms that have been
      shown to drive their chemo-/radioresistance and metastatic potential.

PMID- 24587980
TI  - A review of the recycling of non-metallic fractions of printed circuit boards.
AB  - There is a big waste generation nowadays due to the growing demand for innovation
      and the fact that more and more products have a reduced lifetime, increasing the
      volume of dumps and landfills. Currently, one of the segments of large volume is
      the technology waste, which reflects on the printed circuit boards (PCBs) that
      are the basis of the electronics industry. This type of waste disposal is
      difficult, given that recycling is complex and expensive, because of the
      diversity of existing materials and components, and their difficult separation
      process. Regarding the material involved in PCBs, there are metal fractions (MFs)
      and non-metallic fractions (NMFs), of which the recycling of NMFs is one of the
      most important and difficult processes, because they amount to about 70% of the
      weight of the PCB's waste. In the present paper, a literature review of the
      recycling of non-metallic fractions (NMFs) has been carried out, showing
      different studies and guidelines regarding this type of recycling, emphasizing
      that this type of waste still lacks for further application. 

PMID- 24587982
TI  - Human Tonic and Phasic Smooth Muscle Myosin Isoforms Are Unresponsive to the Loop
      1 Insert.
AB  - Smooth muscle myosin gene products include two isoforms, SMA and SMB, differing
      by a 7-residue peptide in loop 1 (i7) at the myosin active site where ATP is
      hydrolyzed. Using chicken isoforms, previous work indicated that the i7 deletion
      in SMA prolongs strong actin binding by inhibiting active site ingress and egress
      of nucleotide when compared to i7 inserted SMB. Additionally, i7 deletion
      inhibits Pi release associated with the switch 2 closed -> open transition in
      actin-activated ATPase. Switch 2 is far from loop 1 indicating i7 deletion has an
      allosteric effect on Pi release. Chicken SMA and SMB have unknown and robust
      nucleotide-sensitive tryptophan (NST) fluorescence increments, respectively.
      Human SMA and SMB both lack NST increments while Pi release in Ca2+ ATPase is not
      impacted by i7 deletion. The NST reports relay helix movement following
      conformation change in switch 2 but in the open -> closed transition. The NST is
      common to all known myosin isoforms except human smooth muscle. Other independent
      works on human SMA and SMB motility indicate no functional effect of i7 deletion.
      Smooth muscle myosin is a stunning example of species-specific myosin
      structure/function divergence underscoring the danger in extrapolating disease
      linked mutant effects on myosin across species.

PMID- 24587981
TI  - Oxidative stress-mediated effects of angiotensin II in the cardiovascular system.
AB  - Angiotensin II (Ang II), an endogenous peptide hormone, plays critical roles in
      the pathophysiological modulation of cardiovascular functions. Ang II is the
      principle effector of the renin-angiotensin system for maintaining homeostasis in
      the cardiovascular system, as well as a potent stimulator of NAD(P)H oxidase,
      which is the major source and primary trigger for reactive oxygen species (ROS)
      generation in various tissues. Recent accumulating evidence has demonstrated the
      importance of oxidative stress in Ang II-induced heart diseases. Here, we review
      the recent progress in the study on oxidative stress-mediated effects of Ang II
      in the cardiovascular system. In particular, the involvement of Ang II-induced
      ROS generation in arrhythmias, cell death/heart failure, ischemia/reperfusion
      injury, cardiac hypertrophy and hypertension are discussed. Ca2+/calmodulin
      dependent protein kinase II is an important molecule linking Ang II, ROS and
      cardiovascular pathological conditions.

PMID- 24587983
TI  - Comparison of diagnostic accuracy between Octopus 900 and Goldmann kinetic visual
      fields.
AB  - PURPOSE: To determine diagnostic accuracy of kinetic visual field assessment by
      Octopus 900 perimetry compared with Goldmann perimetry. METHODS: Prospective
      cross section evaluation of 40 control subjects with full visual fields and 50
      patients with known visual field loss. Comparison of test duration and area
      measurement of isopters for Octopus 3, 5, and 10 degrees /sec stimulus speeds.
      Comparison of test duration and type of visual field classification for Octopus
      versus Goldmann perimetry. Results were independently graded for presence/absence
      of field defect and for type and location of defect. Statistical evaluation
      comprised of ANOVA and paired t test for evaluation of parametric data with
      Bonferroni adjustment. Bland Altman and Kappa tests were used for measurement of
      agreement between data. RESULTS: Octopus 5 degrees /sec perimetry had comparable
      test duration to Goldmann perimetry. Octopus perimetry reliably detected type and
      location of visual field loss with visual fields matched to Goldmann results in
      88.8% of results (K = 0.775). CONCLUSIONS: Kinetic perimetry requires individual
      tailoring to ensure accuracy. Octopus perimetry was reproducible for
      presence/absence of visual field defect. Our screening protocol when using
      Octopus perimetry is 5 degrees /sec for determining boundaries of peripheral
      isopters and 3 degrees /sec for blind spot mapping with further evaluation of
      area of field loss for defect depth and size.

PMID- 24587984
TI  - Infliximab reverses suppression of cholesterol efflux proteins by TNF-alpha: a
      possible mechanism for modulation of atherogenesis.
AB  - Tumor necrosis factor- (TNF-) alpha is a proinflammatory proatherogenic cytokine.
      Infliximab, an anti-TNF-alpha monoclonal antibody, is effective in treating
      rheumatoid arthritis. However, its impact on cardiovascular burden and lipid
      transport is unclear. The present study investigates the effect of TNF-alpha and
      infliximab on reverse cholesterol transport (RCT) proteins. Uptake of modified
      lipoproteins by macrophages in the vasculature leads to atherogenic foam cell
      formation. RCT is mediated by proteins including ATP binding cassette
      transporters A1 (ABCA1), G1 (ABCG1), liver X receptor- (LXR-) alpha, and 27
      hydroxylase. RCT counteracts lipid overload by ridding cells of excess
      cholesterol. THP-1 human monocytes were incubated with either TNF-alpha alone or
      TNF-alpha with infliximab. Expression of proteins involved in cholesterol efflux
      was analyzed. TNF-alpha significantly reduced both ABCA1 and LXR-alpha mRNA (to
      68.5 +/- 1.59%, P < 0.05, and 41.2 +/- 0.25%, P < 0.01, versus control set as
      100%, resp.). Infliximab nullified the TNF-alpha effect. Results were confirmed
      by Western blot. Infliximab abolished the increase in foam cells induced by TNF
      alpha. TNF-alpha treatment significantly reduces ABCA1 and LXR-alpha expression
      in monocytes, thus bringing about a proatherogenic state. The anti-TNF drug
      infliximab, commonly used in rheumatology, restored RCT proteins. This is the
      first report of an atheroprotective effect of infliximab on RCT in monocytes.

PMID- 24587985
TI  - Assessment of the BD MGIT TBc identification test for the detection of
      Mycobacterium tuberculosis complex in a network of mycobacteriology laboratories.
AB  - We evaluate the performance of the TBcID assay in a panel of 100 acid-fast
      bacilli cultures. Sixty-four isolates were TBcID positive for Mycobacterium
      tuberculosis complex (MTBC), whereas 36 gave negative results. These included 28
      nontuberculous mycobacteria, one nonmycobacterial isolate, one M. tuberculosis,
      and six M. bovis BCG strains. This corresponds to a sensitivity of 90.14%,
      specificity of 100%, and positive and negative predictive values of 100% and
      80.55%, respectively. The test is rapid, easy to perform and interpret, and does
      not require sample preparation or instrumentation. However, a negative result
      does not exclude the presence of a strain belonging to MTBC, especially when
      mutations in mpb64 gene are present or some M. bovis BCG strains are isolated.
      The TBcID showed potential to assist in the identification of MTBC when the
      implementation and usage of molecular methods are often not possible, principally
      in resource-limited countries. 

PMID- 24587986
TI  - Development of a stereotaxic device for low impact implantation of neural
      constructs or pieces of neural tissues into the mammalian brain.
AB  - Implanting pieces of tissue or scaffolding material into the mammalian central
      nervous system (CNS) is wrought with difficulties surrounding the size of tools
      needed to conduct such implants and the ability to maintain the orientation and
      integrity of the constructs during and after their transplantation. Here, novel
      technology has been developed that allows for the implantation of neural
      constructs or intact pieces of neural tissue into the CNS with low trauma. By
      "laying out" (instead of forcibly expelling) the implantable material from a thin
      walled glass capillary, this technology has the potential to enhance neural
      transplantation procedures by reducing trauma to the host brain during
      implantation and allowing for the implantation of engineered/dissected tissues or
      constructs in such a way that their orientation and integrity are maintained in
      the host. Such technology may be useful for treating various CNS disorders which
      require the reestablishment of point-to-point contacts (e.g., Parkinson's
      disease) across the adult CNS, an environment which is not normally permissive to
      axonal growth. 

PMID- 24587987
TI  - Induction of apoptosis in human multiple myeloma cell lines by ebselen via
      enhancing the endogenous reactive oxygen species production.
AB  - Ebselen a selenoorganic compound showing glutathione peroxidase like activity is
      an anti-inflammatory and antioxidative agent. Its cytoprotective activity has
      been investigated in recent years. However, experimental evidence also shows that
      ebselen causes cell death in several cancer cell types whose mechanism has not
      yet been elucidated. In this study, we examined the effect of ebselen on multiple
      myeloma (MM) cell lines in vitro. The results showed that ebselen significantly
      enhanced the production of reactive oxygen species (ROS) accompanied by cell
      viability decrease and apoptosis rate increase. Further studies revealed that
      ebselen can induce Bax redistribution from the cytosol to mitochondria leading to
      mitochondrial membrane potential DeltaPsim changes and cytochrome C release from
      the mitochondria to cytosol. Furtherly, we found that exogenous addition of N
      acetyl cysteine (NAC) completely diminished the cell damage induced by ebselen.
      This result suggests that relatively high concentration of ebselen can induce MM
      cells apoptosis in culture by enhancing the production of endogenous ROS and
      triggering mitochondria mediated apoptotic pathway. 

PMID- 24587988
TI  - mAb CZP-315.D9: an antirecombinant cruzipain monoclonal antibody that
      specifically labels the reservosomes of Trypanosoma cruzi epimastigotes.
AB  - Reservosomes are large round vesicles located at the posterior end of
      epimastigote forms of the protozoan Trypanosoma cruzi, the etiological agent of
      Chagas disease. They are the specific end organelles of the endocytosis pathway
      of T. cruzi, and they play key roles in nutrient uptake and cell differentiation.
      These lysosome-like organelles accumulate ingested macromolecules and contain
      large amounts of a major cysteine proteinase (cruzipain or GP57/51 protein). Aim
      of this study was to produce a monoclonal antibody (mAb) against a recombinant T.
      cruzi cruzipain (TcCruzipain) that specifically labels the reservosomes. BALB/c
      mice were immunized with purified recombinant TcCruzipain to obtain the mAb.
      After fusion of isolated splenocytes with myeloma cells and screening, a mAb was
      obtained by limiting dilution and characterized by capture ELISA. We report here
      the production of a kappa-positive monoclonal IgG antibody (mAb CZP-315.D9) that
      recognizes recombinant TcCruzipain. This mAb binds preferentially to a protein
      with a molecular weight of about 50 kDa on western blots and specifically labels
      reservosomes by immunofluorescence and transmission electron microscopy. The
      monoclonal CZP-315.D9 constitutes a potentially powerful marker for use in
      studies on the function of reservosomes of T. cruzi. 

PMID- 24587989
TI  - Change in anthropometric parameters of the posture of students of physiotherapy
      after three years of professional training.
AB  - INTRODUCTION AND AIM: A physiotherapist's occupation requires high physical
      fitness and a properly functioning neuromuscular system. Working with patients is
      not always performed in accordance with the rules of work ergonomics. The aim of
      this paper was to verify the possible changes in the posture of students of
      physiotherapy after three years of professional training. MATERIAL AND METHODS:
      The sample group consisted of 30 randomly chosen students of physiotherapy. Each
      person was examined twice (at the age of 20 and at the age of 23). Both
      examinations were performed by the same researcher. The ultrasound system ZEBRIS
      Pointer was used for the examination; 17 parameters were analyzed in sagittal
      projection, frontal projection, and transversal projection. RESULTS: Statistical
      analysis revealed positive correlations between the 10 parameters in examination
      1 and examination 2 which means that a person with a relatively higher level of
      obliquity in examination number 1 also had slightly different values in an
      examination conducted three years later. CONCLUSION: Studying physiotherapy and
      physical work with patients resulted in a considerable worsening of the students'
      posture. It is advisable to educate students on ergonomics and the rules of
      safety and hygiene while working as a physiotherapist in order to protect the
      therapists' health.

PMID- 24587991
TI  - Primary headache disorders at a tertiary health facility in Lagos, Nigeria:
      prevalence and consultation patterns.
AB  - BACKGROUND: Primary headaches are underdiagnosed and undertreated, with a
      significant impact on social activities and work. AIM: To determine the last-year
      prevalence and health care utilization pattern of primary headaches at a tertiary
      centre. METHODS: A cross-sectional study was carried out amongst staff of the
      Lagos State University Teaching Hospital in Lagos, Nigeria. 402 staff members
      were selected by simple random sampling and administered a detailed structured
      headache assessment questionnaire. Migraine and tension-type headache were
      diagnosed according to the criteria of the International Headache Society (2004).
      RESULTS: The participants comprised 168 males and 234 females. The mean age was
      36.9 +/- 7.9 years. The overall headache prevalence was 39.3% with female
      predominance (P < 0.0001). Tension-type headache was the most prevalent at 72.8%
      and migraine at 18.9%. Unclassifiable headache constituted 8.2%. Migraine
      headache showed female preponderance (P = 0.000). 80.4% of participants did not
      seek medical consultation compared with 19.6% who did (P = 0.000). Of the latter,
      83.9% consulted the general practitioner (GP), whilst 16.1% consulted the
      neurologist. CONCLUSIONS: Primary headache prevalence is high in our population.
      It is not recognised as that requiring care by most of the staff of this tertiary
      health facility; thus education is required to increase health care utilization.

PMID- 24587992
TI  - Potential activity of 3-(2-chlorophenyl)-1-phenyl-propenonein accelerating wound
      healing in rats.
AB  - Wound healing involves inflammation followed by granular tissue development and
      scar formation. In this study, synthetic chalcone 3-(2-Chlorophenyl)-1-phenyl
      propenone (CPPP) was investigated for a potential role in enhancing wound healing
      and closure. Twenty-four male rats were divided randomly into 4 groups:
      carboxymethyl cellulose (CMC) (0.2 mL), Intrasite gel, and CPPP (25 or 50 mg/mL).
      Gross morphology, wounds treatment with the CPPP, and Intrasite gel accelerate
      the rate of wound healing compared to CMC group. Ten days after surgery, the
      animals were sacrificed. Histological assessment revealed that the wounds treated
      with CPPP showed that wound closure site contained little amount of scar and the
      granulation tissue contained more collagen and less inflammatory cells than wound
      treated with CMC. This finding was confirmed with Masson's trichrome staining.
      The antioxidant defence enzymes catalase (CAT) and superoxide dismutase (SOD)
      were significantly increased in the wound homogenates treated with CPPP (P <
      0.05) compared to CMC treated group. However, in the CPPP treatment group, lipid
      peroxidation (MDA) was significantly decreased (P < 0.05), suggesting that the
      CPPP also has an important role in protection against lipid peroxidation-induced
      skin injury after ten days of treatment with CPPP, which is similar to the values
      of cytokines TGF-beta and TNF-alpha in tissue homogenate. Finally the
      administration of CPPP at a dosage of 25 and 50 mg/kg was suitable for the
      stimulation of wound healing.

PMID- 24587990
TI  - Oxidative stress, prooxidants, and antioxidants: the interplay.
AB  - Oxidative stress is a normal phenomenon in the body. Under normal conditions, the
      physiologically important intracellular levels of reactive oxygen species (ROS)
      are maintained at low levels by various enzyme systems participating in the in
      vivo redox homeostasis. Therefore, oxidative stress can also be viewed as an
      imbalance between the prooxidants and antioxidants in the body. For the last two
      decades, oxidative stress has been one of the most burning topics among the
      biological researchers all over the world. Several reasons can be assigned to
      justify its importance: knowledge about reactive oxygen and nitrogen species
      production and metabolism; identification of biomarkers for oxidative damage;
      evidence relating manifestation of chronic and some acute health problems to
      oxidative stress; identification of various dietary antioxidants present in plant
      foods as bioactive molecules; and so on. This review discusses the importance of
      oxidative stress in the body growth and development as well as proteomic and
      genomic evidences of its relationship with disease development, incidence of
      malignancies and autoimmune disorders, increased susceptibility to bacterial,
      viral, and parasitic diseases, and an interplay with prooxidants and antioxidants
      for maintaining a sound health, which would be helpful in enhancing the knowledge
      of any biochemist, pathophysiologist, or medical personnel regarding this
      important issue. 

PMID- 24587994
TI  - Microbial diversity for biotechnology.

PMID- 24587993
TI  - Carbon nanotubes hybrid hydrogels in drug delivery: a perspective review.
AB  - The use of biologics, polymers, silicon materials, carbon materials, and metals
      has been proposed for the preparation of innovative drug delivery devices. One of
      the most promising materials in this field are the carbon-nanotubes composites
      and hybrid materials coupling the advantages of polymers (biocompatibility and
      biodegradability) with those of carbon nanotubes (cellular uptake, stability,
      electromagnatic, and magnetic behavior). The applicability of polymer-carbon
      nanotubes composites in drug delivery, with particular attention to the
      controlled release by composites hydrogel, is being extensively investigated in
      the present review. 

PMID- 24587995
TI  - Protective effect of alpha-tocopherol isomer from vitamin E against the H2O2
      induced toxicity on dental pulp cells.
AB  - The aim of this study was to evaluate the protective effects of different
      concentrations of vitamin E alpha-tocopherol (alpha-T) isomer against the
      toxicity of hydrogen peroxide (H2O2) on dental pulp cells. The cells (MDPC-23)
      were seeded in 96-well plates for 72 hours, followed by treatment with 1, 3, 5,
      or 10 mM alpha-T for 60 minutes. They were then exposed or not to H2O2 for 30
      minutes. In positive and negative control groups, the cells were exposed to
      culture medium with or without H2O2 (0.018%), respectively. Cell viability was
      evaluated by MTT assay (Kruskal-Wallis and Mann-Whitney tests; alpha = 5%).
      Significant reduction of cell viability (58.5%) was observed in positive control
      compared with the negative control. Cells pretreated with alpha-T at 1, 3, 5, and
      10 mM concentrations and exposed to H2O2 had their viability decreased by 43%,
      32%, 25%, and 27.5%, respectively. These values were significantly lower than
      those observed in the positive control, thereby showing a protective effect of
      alpha-T against the H2O2 toxicity. Overall, the vitamin E alpha-T isomer
      protected the immortalized MDPC-23 pulp cells against the toxic effects of H2O2.
      The most effective cell protection was provided by 5 and 10 mM concentrations of
      alpha-T.

PMID- 24587997
TI  - Contrast media: are there differences in nephrotoxicity among contrast media?
AB  - Iodinated contrast agents are usually classified based upon their osmolality-
      high, low, and isosmolar. Iodinated contrast agents are also nephrotoxic in some
      but not all patients resulting in loss of glomerular filtration rate. Over the
      past 30 years, nephrotoxicity has been linked to osmolality although the precise
      mechanism underlying such a link has been elusive. Improvements in our
      understanding of the pathogenesis of nephrotoxicity and prospective randomized
      clinical trials have attempted to further explore the relationship between
      osmolality and nephrotoxicity. In this review, the basis for our current
      understanding that there are little if any differences in nephrotoxic potential
      between low and isosmolar contrast media will be detailed using data from
      clinical studies.

PMID- 24587996
TI  - Molecular mechanism underlying lymphatic metastasis in pancreatic cancer.
AB  - As the most challenging human malignancies, pancreatic cancer is characterized by
      its insidious symptoms, low rate of surgical resection, high risk of local
      invasion, metastasis and recurrence, and overall dismal prognosis. Lymphatic
      metastasis, above all, is recognized as an early adverse event in progression of
      pancreatic cancer and has been described to be an independent poor prognostic
      factor. It should be noted that the occurrence of lymphatic metastasis is not a
      casual or stochastic but an ineluctable and designed event. Increasing evidences
      suggest that metastasis-initiating cells (MICs) and the microenvironments may act
      as a double-reed style in this crime. However, the exact mechanisms on how they
      function synergistically for this dismal clinical course remain largely elusive.
      Therefore, a better understanding of its molecular and cellular mechanisms
      involved in pancreatic lymphatic metastasis is urgently required. In this review,
      we will summarize the latest advances on lymphatic metastasis in pancreatic
      cancer. 

PMID- 24587998
TI  - Heterogeneous downregulation of angiotensin II AT1-A and AT1-B receptors in
      arterioles in STZ-induced diabetic rat kidneys.
AB  - INTRODUCTION: The renin granulation of kidney arterioles is enhanced in diabetes
      despite the fact that the level of angiotensin II in the diabetic kidney is
      elevated. Therefore, the number of angiotensin II AT1-A and AT1-B receptors in
      afferent and efferent arteriole's renin-positive and renin-negative smooth muscle
      cells (SMC) was estimated. METHOD: Immunohistochemistry at the electron
      microscopic level was combined with 3D stereological sampling techniques.
      RESULTS: In diabetes the enhanced downregulation of AT1-B receptors in the renin
      positive than in the renin-negative SMCs in both arterioles was resulted: the
      significant difference in the number of AT1 (AT1-A + AT1-B) receptors between the
      two types of SMCs in the normal rats was further increased in diabetes and in
      contrast with the significant difference observed between the afferent and
      efferent arterioles in the normal animals, there was no such difference in
      diabetes. CONCLUSIONS: The enhanced downregulation of the AT1-B receptors in the
      renin-negative SMCs in the efferent arterioles demonstrates that the regulation
      of the glomerular filtration rate by the pre- and postglomerular arterioles is
      changed in diabetes. The enhanced downregulation of the AT1-B receptors in the
      renin-positive SMCs in the arterioles may result in an enhanced level of renin
      granulation in the arterioles.

PMID- 24587999
TI  - Immunomodulation in human dendritic cells leads to induction of interferon-gamma
      production by Leishmania donovani derived KMP-11 antigen via activation of NF
      kappaB in Indian kala-azar patients.
AB  - Dendritic cells (DCs) and macrophages (MPhis) are well-known antigen presenting
      cells with an ability to produce IL-12 which indicates that they have potential
      of directing acquired immunity toward a Th1-biased response. The aim of this
      study was to examine the effect of Leishmania specific KMP-11 antigen through
      comparison of immune responses after presentation by DCs and MPhis to T cells in
      Indian patients with VL. Patients with DCS and MPhis were directed against a
      purified Leishmania donovani antigen (KMP-11) and phytohaemagglutinin (PHA). The
      cytokines (IL-12, IL-10, and TGF-beta) producing abilities of the DCs and MPhis
      against these antigens were determined by flow cytometry. The transcription
      factor (NF-kappaB) and T-cell cytokine support (IFN-gamma, IL-10), which could be
      significant in effector immune function, were also determined. Severe hindrance
      in the immune protection due to Leishmania parasites, as revealed by decreased
      expression of IL-12 and upregulation of IL-10 and TGF-beta expression in the
      MPhis compared to DCs, occurred in VL patients. The production of IL-12 in
      response to L. donovani KMP-11 antigen was increased in DCs which was reduced in
      MPhis of VL patients. In contrast, the presentation of KMP-11 antigen by DCs to T
      lymphocytes in VL patients significantly increased the IFN-gamma produced by
      these immune cells, whereas the levels of IL-10 were significantly elevated after
      presentation of KMP-11 antigen by MPhis. The VL patients were observed with
      severely dysfunctional MPhis in terms of NF-kappaB activity that could be
      recovered only after stimulation of DCs with L. donovani KMP-11 antigen.
      Immunologically the better competitiveness of KMP-11 antigen through a dendritic
      cell delivery system may be used to revert T-cell anergy, and control strategy
      can be designed accordingly against kala-azar.

PMID- 24588000
TI  - Assessment of Mycobacterium bovis deleted in p27-p55 virulence operon as
      candidate vaccine against tuberculosis in animal models.
AB  - A Mycobacterium bovis knockout in p27-p55 operon was tested as an
      antituberculosis experimental vaccine in animal models. The mutant MbDeltap27-p55
      was significantly more attenuated in nude mice than its parental strain but more
      virulent than BCG Pasteur. Challenge experiments in mice and guinea pigs using M.
      bovis or M. tuberculosis strains showed similar protection conferred by
      MbDeltap27-p55 mutant than BCG in terms of pathology and bacterial loads in
      spleen but lower protection than BCG in lungs. When tested in cattle, MbDeltap27
      p55 did not induce IL-2 expression and induced a very low production of IFNgamma,
      suggesting that the lack of P27/P55 reduces the capacity of M. bovis of
      triggering an adequate Th1 response. 

PMID- 24588002
TI  - Principal Components Analysis of Scalar, Vector, and Mesh Vertex Data.
AB  - This document describes a contribution to the Insight Toolkit intended to support
      the analysis of the principal components of data sets, optionally point data
      associated with the vertices of a mesh. This paper is accompanied with the source
      code, input data, parameters and output data that we used for validating the
      implementation described in this paper. This adheres to the fundamental principle
      that scientific publications must facilitate reproducibility of the reported
      results.

PMID- 24588001
TI  - Modulation of wolframin expression in human placenta during pregnancy: comparison
      among physiological and pathological states.
AB  - The WFS1 gene, encoding a transmembrane glycoprotein of the endoplasmic reticulum
      called wolframin, is mutated in Wolfram syndrome, an autosomal recessive disorder
      defined by the association of diabetes mellitus, optic atrophy, and further organ
      abnormalities. Disruption of the WFS1 gene in mice causes progressive beta-cell
      loss in the pancreas and impaired stimulus-secretion coupling in insulin
      secretion. However, little is known about the physiological functions of this
      protein. We investigated the immunohistochemical expression of wolframin in human
      placenta throughout pregnancy in normal women and diabetic pregnant women. In
      normal placenta, there was a modulation of wolframin throughout pregnancy with a
      strong level of expression during the first trimester and a moderate level in the
      third trimester of gestation. In diabetic women, wolframin expression was
      strongly reduced in the third trimester of gestation. The pattern of expression
      of wolframin in normal placenta suggests that this protein may be required to
      sustain normal rates of cytotrophoblast cell proliferation during the first
      trimester of gestation. The decrease in wolframin expression in diabetic placenta
      suggests that this protein may participate in maintaining the physiologic glucose
      homeostasis in this organ.

PMID- 24588003
TI  - Trace vapour detection at room temperature using Raman spectroscopy.
AB  - A miniaturized flow-through system consisting of a gold coated silicon substrate
      based on enhanced Raman spectroscopy has been used to study the detection of
      vapour from model explosive compounds. The measurements show that the
      detectability of the vapour molecules at room temperature depends sensitively on
      the interaction between the molecule and the substrate. The results highlight the
      capability of a flow system combined with Raman spectroscopy for detecting low
      vapour pressure compounds with a limit of detection of 0.2 ppb as demonstrated by
      the detection of bis(2-ethylhexyl)phthalate, a common polymer additive emitted
      from a commercial polyvinyl chloride (PVC) tubing at room temperature. 

PMID- 24588004
TI  - Methanol-induced conformation transition of gland fibroin monitored by FTIR
      spectroscopy and terahertz spectroscopy.
AB  - Silk fibroin extracted from the gland of Bombyx mori silkworm is employed as an
      ideal system to investigate its conformation transition in methanol/D2O solution.
      The transition process was monitored by Fourier transform infrared (FTIR)
      spectroscopy coupled with terahertz time domain spectroscopy (THz-TDS). Analysis
      of FTIR spectra suggests that, with increasing time of treatment, an increasing
      band at 1634 cm(-1) is observed indicating the formation of beta-pleated sheets
      coincident with the loss of intensity of a band at 1673 cm(-1) indicating
      decrease of the random coil structure. In addition, there is a burst phase of 33%
      occurring during the first 2 minutes when the gland fibroin membranes are
      immersed into methanol/D2O solution. THz spectra present distinct features for
      conformations of silk fibroin, in combination with the results obtained from
      FTIR; the peaks observed at 1.54 THz (51 cm(-1)), 1.67 THz (55 cm(-1)), and 1.84
      THz (61 cm(-1)) can be attributed to a beta-pleated sheet, alpha-helix, and
      random coil, respectively. Intensity change of bands centered at 1.54 THz and
      1.84 THz confirms the formation of the beta-pleated sheet and the disappearance
      of the random coil. Kinetic curves obtained from THz spectra indicate that the
      methanol-induced conformation transition from the random coil to the beta-pleated
      sheet is fitted with an exponential function. The results suggest that THz-TDS
      presents great potential as a complementary approach in studying the secondary
      structure of a protein, providing significant insight into the silk-spinning
      process in vivo. 

PMID- 24588005
TI  - [Does the surgeon need the history of his specialization?].

PMID- 24588006
TI  - [Flebology in the ancient world].

PMID- 24588007
TI  - [The diagnostic and treatment of visceral and renal arterial aneurisms].

PMID- 24588008
TI  - The authors reply.

PMID- 24588009
TI  - [Amosov N. M. (to the 100th anniversary of birth)].

PMID- 24588010
TI  - [The contribution of V. F. Voino-Iasenetskii (Archbishop Luka) to the military
      surgery].

PMID- 24588011
TI  - [Science of life and life in science (on the occasion of 90th anniversary of
      professor N.N. Bazhanov].

PMID- 24588012
TI  - Durable HIV RNA resuppression after virologic failure while  remaining on a first
      line regimen: a cohort study.
AB  - Adherence interventions are a recommended strategy to salvage failing
      antiretroviral therapy without regimen change. We assessed the durability of
      resuppression when using this approach. Of 300 patients who resuppressed on the
      same regimen (41% of all those with virologic failure), 148 (45%) remained
      suppressed during follow-up for a median of 2.4 years (interquartile range [IQR]:
      1.1, 4.0). Resuppression can be durable following viraemia without a switch in
      antiretroviral therapy regimen.

PMID- 24588013
TI  - Emergence of FGFR family gene fusions as therapeutic targets in a wide spectrum
      of solid tumours.
AB  - The emergence of fibroblast growth factor receptor (FGFR) family fusions across
      diverse cancers has brought attention to FGFR-derived cancer therapies. The
      discovery of the first recurrent FGFR fusion in glioblastoma was followed by
      discoveries of FGFR fusions in bladder, lung, breast, thyroid, oral, and prostate
      cancers. Drug targeting of FGFR fusions has shown promising results and should
      soon be translating into clinical trials. FGFR fusions form as a result of
      various mechanisms - predominantly deletion for FGFR1, translocation for FGFR2,
      and tandem duplication for FGFR3. The ability to exploit the unique targetability
      of FGFR fusions proves that FGFR-derived therapies could have a promising future
      in cancer therapeutics. Drug targeting of fusion genes has proven to be an
      extremely effective therapeutic approach for cancers such as the recurrent BCR
      ABL1 fusion in chronic myeloid leukaemia. The recent discovery of recurrent FGFR
      family fusions in several cancer types has brought to attention the unique
      therapeutic potential for FGFR-positive patients. Understanding the diverse
      mechanisms of FGFR fusion formation and their oncogenic potential will shed light
      on the impact of FGFR-derived therapy in the future.

PMID- 24588014
TI  - Diffuse alopecia in an adolescent female: tinea capitis.
AB  - "Black dot" tinea capitis is a common cause of alopecia in young patients. It is
      most commonly caused by a dermatophyte infection with Trichophyton tonsurans.
      This entity can be easily distinguished from alopecia areata with the use of
      hair/scalp dermoscopy. The use of oral terbinafine is effective in resolving the
      infection.

PMID- 24588016
TI  - [Sentinel lymph node in pulmonary carcinoma. Molecular study after radioisotope
      detection].
AB  - INTRODUCTION: Metastatic lymph node affectation is the main prognostic factor in
      localized lung cancer. Pathological study of the obtained samples even after an
      adequate lymphadenectomy, present tumoral relapses of 40% of stage I patients
      after oncological curative surgery. In this paper we have studied micrometastasis
      in the sentinel lymph node by molecular methods in patients with stage I lung
      cancer. MATERIAL AND METHODS: The sentinel node was marked by injecting
      peritumorally performed just after performing the thoracotomy with 2 mCi of
      nanocoloid of albumin (Nanocol(r)) marked with 99mTc in 0.3 ml. Guided with a
      Navigator(r) gammagraphic sensor, we proceeded to its resection. RNA of the
      tissue was extracted and the presence of genes CEACAM5, PLUNC and CK7 in mRNA was
      studied. RESULTS: Twenty nine 29 patients were included. Of the tested genes,
      CEACAM5 and PLUNC were the ones that showed a high expression in lung tissue. Of
      the 29 analyzed sentinel lymph nodes, 7 (24%) were positive in the molecular
      study. A positive sentinel lymph node was found in 4/7 adenocarcinomas and 3/12
      squamous-cell tumors. Affected lymph nodes were: station 5 (1/3), station 7
      (0/6), station 9 (0/1); station 10 (5/11); station 11 (1/1). CONCLUSIONS:
      Detection of sentinel node in patients with stage I lung cancer by marking with
      radioisotope is a feasible technique. The application of molecular techniques
      shows the tumoral affectation in cases staged as stage I.

PMID- 24588017
TI  - Response.

PMID- 24588015
TI  - Shifting paradigms on the role of connexin43 in the skeletal response to
      mechanical load.
AB  - Gap junctions (GJs) are membrane-spanning channels that allow for the movement of
      small molecules across cell membranes. Connexin43 (Cx43) is the predominant GJ
      protein in bone. In vitro studies suggest that gap junctional intercellular
      communication (GJIC) sensitizes bone cells to mechanical signals. Additionally,
      mechanical signals detected by osteocytes are communicated to osteoblasts via
      GJIC, and osteocytic Cx43 hemichannels release anabolic factors, such as PGE2 and
      ATP, in response to mechanical load. These findings and others have led to near
      consensus among researchers in the field that GJIC, hemichannels or connexins
      facilitate the anabolic response of bone to mechanical load and, in their
      absence, bone would be less sensitive to load. However, recent in vivo evidence
      suggests the opposite is true. Studies from our laboratory and others demonstrate
      that Cx43-deficient mice have an increased anabolic response to mechanical load
      and are protected against the catabolic effects of mechanical unloading. These
      developments suggest a paradigm shift in our understanding of connexins, GJIC,
      and mechanotransduction in bone. That is, inhibiting bone cell Cx43 expression or
      GJIC has a beneficial effect on bone's response to its mechanical environment,
      preserving bone during unloading and enhancing its formation during loading.
      Here, we review literature in support of this hypothesis and suggest a mechanism
      by which Cx43, through interaction with WNT/beta-catenin signaling, moderates
      both arms of bone remodeling.

PMID- 24588020
TI  - Myelination: switching modes of myelination.

PMID- 24588019
TI  - Functional MRI-based lie detection: scientific and societal challenges.
AB  - Functional MRI (fMRI)-based lie detection has been marketed as a tool for
      enhancing personnel selection, strengthening national security and protecting
      personal reputations, and at least three US courts have been asked to admit the
      results of lie detection scans as evidence during trials. How well does fMRI
      based lie detection perform, and how should the courts, and society more
      generally, respond? Here, we address various questions - some of which are based
      on a meta-analysis of published studies - concerning the scientific state of the
      art in fMRI-based lie detection and its legal status, and discuss broader ethical
      and societal implications. We close with three general policy recommendations.

PMID- 24588021
TI  - Anticipating the effect of the Patient Protection and Affordable Care Act for
      patients with urologic cancer.
AB  - The Affordable Care Act seeks to overhaul the US health care system by providing
      insurance for more Americans, improving the quality of health care delivery, and
      reducing health care expenditures. Although the law's intent is clear, its
      implementation and effect on patient care remains largely undefined. Herein, we
      discuss major components of the Affordable Care Act, including the proposed
      insurance expansion, payment and delivery system reforms (e.g., bundled payments
      and Accountable Care Organizations), and other reforms relevant to the field of
      urologic oncology. We also discuss how these proposed reforms may affect patients
      with urologic cancers.

PMID- 24588022
TI  - Big Data-and its contributions to peri-operative medicine.

PMID- 24588018
TI  - Synaptic changes induced by melanocortin signalling.
AB  - The melanocortin system has a well-established role in the regulation of energy
      homeostasis, but there is growing evidence of its involvement in memory,
      nociception, mood disorders and addiction. In this Review, we focus on the role
      of the melanocortin 4 receptor and provide an integrative view of the molecular
      mechanisms that lead to melanocortin-induced changes in synaptic plasticity
      within these diverse physiological systems. We also highlight the importance of
      melanocortin peptides and receptors in chronic pain syndromes, memory
      impairments, depression and drug abuse, and the possibility of targeting them for
      therapeutic purposes.

PMID- 24588023
TI  - The association between tranexamic acid and convulsive seizures after cardiac
      surgery: a multivariate analysis in 11 529 patients.
AB  - Because of a lack of contemporary data regarding seizures after cardiac surgery,
      we undertook a retrospective analysis of prospectively collected data from 11 529
      patients in whom cardiopulmonary bypass was used from January 2004 to December
      2010. A convulsive seizure was defined as a transient episode of disturbed brain
      function characterised by abnormal involuntary motor movements. Multivariate
      regression analysis was performed to identify independent predictors of
      postoperative seizures. A total of 100 (0.9%) patients developed postoperative
      convulsive seizures. Generalised and focal seizures were identified in 68 and 32
      patients, respectively. The median (IQR [range]) time after surgery when the
      seizure occurred was 7 (6-12 [1-216]) h and 8 (6-11 [4-18]) h, respectively.
      Epileptiform findings on electroencephalography were seen in 19 patients.
      Independent predictors of postoperative seizures included age, female sex, redo
      cardiac surgery, calcification of ascending aorta, congestive heart failure, deep
      hypothermic circulatory arrest, duration of aortic cross-clamp and tranexamic
      acid. When tested in a multivariate regression analysis, tranexamic acid was a
      strong independent predictor of seizures (OR 14.3, 95% CI 5.5-36.7; p < 0.001).
      Patients with convulsive seizures had 2.5 times higher in-hospital mortality
      rates and twice the length of hospital stay compared with patients without
      convulsive seizures. Mean (IQR [range]) length of stay in the intensive care unit
      was 115 (49-228 [32-481]) h in patients with convulsive seizures compared with 26
      (22-69 [14-1080]) h in patients without seizures (p < 0.001). Convulsive seizures
      are a serious postoperative complication after cardiac surgery. As tranexamic
      acid is the only modifiable factor, its administration, particularly in doses
      exceeding 80 mg.kg(-1), should be weighed against the risk of postoperative
      seizures.

PMID- 24588024
TI  - Prophylactic phenylephrine for caesarean section under spinal anaesthesia:
      systematic review and meta-analysis.
AB  - We conducted a systematic review to determine the harm and benefit associated
      with prophylactic phenylephrine for caesarean section under spinal anaesthesia.
      We included 21 randomised controlled trials with 1504 women. The relative risk
      (95% CI) of hypotension with phenylephrine infusion - as defined by authors -
      before delivery was 0.36 (0.18-0.73) vs placebo, p = 0.004; 0.58 (0.39-0.88) vs
      an ephedrine infusion, p = 0.009; and 0.73 (0.55-0.96) when added to an ephedrine
      infusion, p = 0.02. After delivery, the relative risks of hypotension and nausea
      and vomiting with phenylephrine compared with placebo were 0.37 (0.19-0.71), p =
      0.003, and 0.39 (0.17-0.91), p = 0.03, respectively. There was no evidence that
      hypertension, bradycardia or neonatal endpoints were affected. Phenylephrine
      reduced the risk for hypotension and nausea and vomiting after spinal doses of
      bupivacaine generally exceeding 8 mg, but there was no evidence that it reduced
      other maternal or neonatal morbidities.

PMID- 24588025
TI  - Omnia praeclara rara. The quest for ingenol heats up.

PMID- 24588026
TI  - Self-host blue-emitting iridium dendrimer with carbazole dendrons: nondoped
      phosphorescent organic light-emitting diodes.
AB  - A blue-emitting iridium dendrimer, namely B-G2, has been successfully designed
      and synthesized with a secondgeneration oligocarbazole as the dendron, which is
      covalently attached to the emissive tris[2-(2,4-difluorophenyl)
      pyridyl]iridium(III) core through a nonconjugated link to form an efficient self
      host system in one dendrimer. Unlike small molecular phosphors and other
      phosphorescent dendrimers, B-G2 shows a continuous enhancement in the device
      efficiency with increasing doping concentration. When using neat B-G2 as the
      emitting layer, the nondoped device is achieved without loss in efficiency, thus
      giving a state-of-art EQE as high as 15.3% (31.3 cdA1, 28.9 lmW1) along with CIE
      coordinates of (0.16, 0.29).

PMID- 24588027
TI  - Interferons in the central nervous system: a few instruments play many tunes.
AB  - Interferons (IFNs) are implicated as an important component of the innate immune
      system influencing viral infections, inflammation, and immune surveillance. We
      review here the complex biological activity of IFNs in the central nervous system
      (CNS) and associated glial-immune interactions, with focus specifically on the
      Type I IFNs in physiological and pathological conditions. IFN-alpha and IFN-beta
      are the predominant Type I IFNs in the CNS. They are produced in the CNS by glial
      cells, mostly microglia and astrocytes, as well as by neurons. A variety of
      mechanisms stimulate IFN production in glial cells, including innate stimuli from
      Toll-like and other receptors, which can recognize endogenous entities, as well
      as pathogens. We will review evidence that differential signaling by IFN-alpha
      versus IFN-beta through the common heterodimeric receptor IFNAR is the basis for
      CNS-selective Type I IFN response, and the capacity of CNS glial cells to produce
      and respond to Type I IFN. Differential signaling outcomes of IFN-alpha and IFN
      beta, which have been ascribed to differential affinity for IFNAR1 and IFNAR2,
      determine whether Type I IFN exert pathogenic or protective roles in the CNS.
      These points will be discussed with reference to selected neurological diseases,
      and effects of Type I IFN on the integrity of the blood-brain barrier.

PMID- 24588028
TI  - Retraction: "Jagged1 regulates the activation of astrocytes via modulation of
      NFkappaB and JAK/STAT/SOCS pathways" by Eleonora Morga, Laila Mouad-Amazzal, Paul
      Felten, Tony Heurtaux, Mike Moro, Alessandro Michelucci, Sebastien Gabel, Luc
      Grandbarbe, and Paul Heuschling.

PMID- 24588029
TI  - [Injuries of the upper extremities].

PMID- 24588030
TI  - [Foveoschisis in highly myopic eyes: clinical and tomographic features].
AB  - INTRODUCTION: Foveoschisis is a rare condition in highly myopic eyes,
      characterized by intra-retinal cleavage associated with abnormalities of the
      vitreous cortex and occasionally cortical retraction. The natural history of
      foveoschisis is unpredictable. The functional prognosis is often favorable after
      surgical treatment. MATERIALS AND METHODS: We report 7 cases of macular
      retinoschisis in highly myopic eyes. We describe the optical coherence
      tomographic features as well as associated signs. The correlation with visual
      acuity was assessed. RESULTS: Foveoschisis was undetected on clinical exam and
      visualized only on optical coherence tomography (OCT) in 4 cases. Mean central
      foveal thickness was 540 , mean visual acuity was 1/10-P10. The thicker the
      macula was, the worse was the visual acuity. The presenceor absence of serous
      retinal detachment did not affect visual acuity, whereas an epiretinal membrane
      or retraction of the vitreous cortex appeared to induce visual loss. CONCLUSION:
      OCT has been demonstrated to be particularly useful for the diagnosis of visual
      loss in the high myope, notably in the case of foveoschisis. Anatomic-functional
      correlations in high myopic foveoschisis are not yet well clarified. Posterior
      pole retinal detachment and macular hole are the most serious complications.

PMID- 24588031
TI  - [Effect of acupuncture intervention on learning-memory ability and cerebral
      superoxide dismutase activity and malonaldehyde concentration in chronic fatigue
      syndrome rats].
AB  - OBJECTIVE: To observe the effect of acupuncture intervention on learning-memory
      ability and cerebral superoxide dismutase (SOD) activity and malonaldehyde (MDA)
      content in chronic fatigure syndrome (CFS) rats so as to reveal its mechanism
      underlying improvement of clinical CFS. METHODS: Thirty-six male SD rats were
      randomly divided into control group, model group and acupuncture group (n = 12 in
      each group). CFS model was established by double stress stimulation of suspending
      (1.0 - 2.5 h increasing gradually) and forced swimming [Morris water maze tasks,
      7 min in (10 +/- 1) degrees C water], once daily for 12 days. Manual acupuncture
      stimulation was applied to "Baihui" (CV 20), bilateral "Zusanli" (ST 36) and
      "Sanyinjiao" (SP 6), once daily for 21 days (with 3 days' interval between every
      two weeks). Learning-memory ability was determined by Morris water maze tests,
      and SOD activity and MDA concentration in the brain tissues were detected by
      xanthine oxidase method and thiobarbiturif acid method, respectively. RESULTS:
      Compared with the control group, the escape latencies at time-points of day 1, 2,
      3, 4 and 5 of Morris water maze tests were significantly longer, the target
      platform crossing times were markedly fewer and the target platform quadrant
      staying time obviously shorter, cerebral SOD activity was considerably decreased,
      and cerebral MDA content remarkably increased in the model group (P < 0.05, P <
      0.01). Following acupuncture intervention, the escape latencies at time-points of
      day 1, 2, 3, 4 and 5 were significantly decreased, both target platform crossing
      times and staying time, and cerebral SOD activity were apparently increased, as
      well as cerebral MDA level was markedly lowered in comparison with the model
      group (P<0.05, P<0.01). CONCLUSION: Acupuncture intervention can improve the
      learning-memory ability in CFS rats, which may be related to its effect in
      regulating metabolism of free radicals in the brain tissues.

PMID- 24588032
TI  - War on Carcinogens: industry disputes human relevance of chemicals causing cancer
      in laboratory animals based on unproven hypotheses, using kidney tumors as an
      example.
AB  - Evidence from studies in animals is essential for identifying chemicals likely to
      cause or contribute to many diseases in humans, including cancers. Yet, to avoid
      or delay the implementation of protective public health standards, the chemical
      industry typically denies cancer causation by agents they produce. The spurious
      arguments put forward to discount human relevance are often based on inadequately
      tested hypotheses or modes of action that fail to meet Bradford Hill criteria for
      causation. We term the industry attacks on the relevance of animal cancer
      findings as the "War on Carcinogens." Unfortunately, this tactic has been
      effective in preventing timely and appropriate health protective actions on many
      economically important yet carcinogenic chemicals, including: arsenic, asbestos,
      benzene, 1,3-butadiene, formaldehyde, methylene chloride, phthalates, tobacco
      usage, trichloroethylene [TCE], and others. Recent examples of the "War on
      Carcinogens" are chemicals causing kidney cancer in animals. Industry consultants
      argue that kidney tumor findings in rats with exacerbated chronic progressive
      nephropathy (CPN) are not relevant to humans exposed to these chemicals. We
      dispute and dismiss this unsubstantiated claim with data and facts, and divulge
      unprofessional actions from a leading toxicology journal.

PMID- 24588033
TI  - Health issues of female foreign domestic workers: a systematic review of the
      scientific and gray literature.
AB  - BACKGROUND: Although the number of female foreign domestic workers (FDWs) is
      increasing worldwide, little is known about their health issues. OBJECTIVE: To
      systematically review the literature on health issues of female FDWs to ascertain
      the problems studied, identify limitations, and suggest future research and
      policy implications. METHODS: A systematic database (PubMed, EBSCO Host, and
      Google Scholar) and bibliographic search identified the English-language
      scientific and gray literature published during 1990-2012 addressing health
      issues of female FDWs living with the family of the employer, using qualitative
      and/or quantitative research methods. Studies in which female FDWs constituted
      less than half of the participants were excluded. RESULTS: The health issues
      studied and identified were adverse work conditions and associated health
      problems (such as physical, verbal, and sexual abuse at the workplace, caregiving
      tasks associated with musculoskeletal strain, and chemical exposure associated
      with respiratory difficulty), mental health (psychotic, neurotic, and mood
      disorders), infectious diseases (most of the studies were on intestinal parasitic
      infections), and health knowledge/attitudes/practices (most of the studies were
      in context of sexual and reproductive health). Most of the studies were medical
      record reviews or questionnaire-based surveys utilizing convenience sampling or
      qualitative interviews/focus group discussions. CONCLUSION: Female FDWs face
      numerous health problems. Studies on representative, possibly longitudinal,
      samples of female FDWs focusing on specific health conditions are needed to
      better understand the epidemiology of such conditions. Concerted efforts through
      the governments of both labor-sending and host countries are required to improve
      the health, work conditions, and safety of this vulnerable group of women.

PMID- 24588034
TI  - Working conditions and environmental exposures among electronic waste workers in
      Ghana.
AB  - OBJECTIVE: To investigate and describe informal e-waste recycling and working
      conditions at Agbogbloshie, Accra, Ghana. METHODS: We conducted in-depth
      interviews which were qualitatively analysed from a grounded theory perspective.
      RESULTS: Workers obtained e-waste from the various residential areas in Accra,
      then dismantled and burned them in open air to recover copper, aluminum, steel,
      and other products for sale to customers on-site or at the nearby Agbogbloshie
      market. The processers worked under unhealthy conditions often surrounded by
      refuse and human excreta without any form of protective gear and were thus
      exposed to frequent burns, cuts, and inhalation of highly contaminated fumes. We
      observed no form of social security/support system for the workers, who formed
      informal associations to support one another in times of difficulty. CONCLUSIONS:
      e-waste recycling working conditions were very challenging and presented serious
      hazards to worker health and wellbeing. Formalizing the e-waste processing
      activities requires developing a framework of sustainable financial and social
      security for the e-waste workers, including adoption of low-cost, socially
      acceptable, easy-to-operate, and cleaner technologies that would safeguard the
      health of the workers and the general public.

PMID- 24588035
TI  - MetLife and its corporate allies: dust diseases and the manipulation of science.
AB  - BACKGROUND: The dust diseases silicosis and asbestosis were the first
      occupational diseases to have widespread impact on workers. Knowledge that
      asbestos and silica were hazardous to health became public long after the
      industry knew of the health concerns. This delay was largely influenced by the
      interests of Metropolitan Life Insurance Company (MetLife). OBJECTIVES: To
      understand how MetLife influenced the science and politics of asbestos and silica
      exposure in the first half of the twentieth century. METHODS: We examined
      previously secret corporate documents produced in litigation, deposition, and
      trial testimony, as well as published scholarship. RESULTS: MetLife established
      itself as an authority in public and industrial health in the early part of the
      twentieth century, gaining the trust of the public and government. They were able
      to use this trust and authority to avoid financial loss, including the firing of
      sick workers, and avoid legal liability by organizing a network of experts to
      testify on their behalf in silica- and asbestos-related damage suits. They
      further manipulated the results of scientific findings from major research
      institutions, delaying important knowledge about the asbestos-cancer
      relationship. They also influenced law and public policy through writing and
      implementing worker compensation laws in numerous states and concocting an
      arbitrary "protective" standard to monitor asbestos exposure. This standard was
      known by MetLife to not protect against disease. CONCLUSIONS: The actions of
      MetLife and its allies had real human and scientific consequences and an effect
      on the industry lasting until now.

PMID- 24588036
TI  - Urinary levoglucosan as a biomarker for woodsmoke exposure in wildland
      firefighters.
AB  - BACKGROUND: Levoglucosan, a sugar anhydride and a combustion breakdown product of
      cellulose is a dominant organic constituent of particles in woodsmoke. After
      exposure, levoglucosan is excreted unmetabolized in urine. OBJECTIVE: Urinary
      levoglucosan was assessed as a biomarker of occupational woodsmoke exposure among
      wildland firefighters. METHODS: Urine samples were collected from wildland
      firefighters before and after their work-shifts on days when they worked at
      prescribed burns. A total of 97 pairs of pre- and post-shift urine samples were
      collected from 19 firefighters over 10 prescribed burn shifts. The urine samples
      were analyzed to determine whether there was an increase in the concentration of
      levoglucosan from pre- to post-shift after the firefighters had worked at the
      prescribed burns. RESULTS: Overall, there was an increase in both the urinary
      volume-based and creatinine corrected levoglucosan concentrations from pre- to
      post-shift (P < 0.05). However, the direction of change in the concentrations was
      not consistent. There were increases in urinary levoglucosan concentration from
      pre- to post-shift in 63% of the person-day samples, and in only 58% of the
      person-day samples for the creatinine corrected concentrations. CONCLUSION:
      Although there was an overall increase in urinary concentrations of levoglucosan,
      results suggest that other sources apart from woodsmoke affected the urinary
      levels of this biomarker in wildland firefighters. Therefore, urinary
      levoglucosan may not be effective as a biomarker of woodsmoke exposure in this
      setting.

PMID- 24588037
TI  - Airborne bacteria and fungi associated with waste-handling work.
AB  - BACKGROUND: Municipal workers handling household waste are potentially exposed to
      a variety of toxic and pathogenic substances, in particular airborne bacteria,
      gram-negative bacteria (GNB), and fungi. However, relatively little is known
      about the conditions under which exposure is facilitated. METHODS: This study
      assessed levels of airborne bacteria, GNB, and fungi, and examined these in
      relation to the type of waste-handling activity (collection, transfer, transport,
      and sorting at the waste preprocessing plant), as well as a variety of other
      environmental and occupational factors. Airborne microorganisms were sampled
      using an Andersen single-stage sampler equipped with agar plates containing the
      appropriate nutritional medium and then cultured to determine airborne levels.
      Samples were taken during collection, transfer, transport, and sorting of
      household waste. Multiple regression analysis was used to identify environmental
      and occupational factors that significantly affect airborne microorganism levels
      during waste-handling activities. RESULTS: The "type of waste-handling activity"
      was the only factor that significantly affected airborne levels of bacteria and
      GNB, accounting for 38% (P = 0.029) and 50% (P = 0.0002) of the variation
      observed in bacteria and GNB levels, respectively. In terms of fungi, the type of
      waste-handling activity (R2 = 0.76) and whether collection had also occurred on
      the day prior to sampling (P < 0.0001, R2 = 0.78) explained most of the observed
      variation. Given that the type of waste-handling activity was significantly
      correlated with levels of bacteria, GNB, and fungi, we suggest that various
      engineering, administrative, and regulatory measures should be considered to
      reduce the occupational exposure to airborne microorganisms in the waste-handling
      industry.

PMID- 24588039
TI  - Using exhaled carbon monoxide and carboxyhemoglobin to evaluate the effectiveness
      of a chimney stove model in Peru.
AB  - BACKGROUND: Measurement of biological indicators of physiological change may be
      useful in evaluating the effectiveness of stove models, which are intended to
      reduce indoor smoke exposure and potential health effects. OBJECTIVES: We
      examined changes in exhaled carbon monoxide (CO), percentage carboxy-hemoglobin,
      and total hemoglobin in response to the installation of a chimney stove model by
      the Juntos National Program in Huayatan, Peru in 2008. METHODS: Biomarkers were
      measured in a convenience sample comprising 35 women who met requirements for
      participation, and were measured before and three weeks after installation of a
      chimney stove. The relationships between exposure to indoor smoke and biomarker
      measurements were also analyzed using simple linear regression models. RESULTS:
      Exhaled CO reduced from 6.71 ppm (95% CI 5.84-7.71) to 3.14 ppm (95% CI 2.77
      3.66) three weeks after stove installation (P < 0.001) while % COHb reduced from
      1.76% (95% CI 1.62-1.91) to 1.18% (95% CI 1.12-1.25; P < 0.001). Changes in
      exhaled CO and % COHb from pre- to post-chimney stove installation were not
      correlated with corresponding changes in exposure to CO and PM2.5 even though the
      exposures also reduced after stove installation. CONCLUSION: Exhaled CO and %
      COHb both showed improvement with reduction in concentration after the
      installation of the chimney cook stoves, indicating a positive physiological
      response subsequent to the intervention.

PMID- 24588040
TI  - Framing and blaming: construction of workplace injuries by legislators in
      Alberta, Canada.
AB  - BACKGROUND: Legislators in the Canadian province of Alberta have successfully
      resisted pressure to increase state injury-prevention efforts. OBJECTIVES: This
      study seeks to identify the narratives used by legislators to manage political
      pressure for increased injury-prevention efforts. METHODS: Narrative analysis of
      legislative transcripts from 2000 to 2012. RESULTS: Three narratives are
      identified in the data: (1) injuries are caused by ignorance and inattention, (2)
      workplaces are safe and getting safer, and (3) risk is inevitable and mitigation
      is (too) expensive. Each narrative has 2-4 subcomponents. CONCLUSIONS: The
      consistency of the messages delivered by legislators over time suggests an
      intentional effort to frame workplace injury in ways that manage political
      pressure for greater state efforts to prevent workplace injuries while
      maintaining the government's legitimacy. The narratives used by legislators draw
      on widely held beliefs about workplace injuries, including the careless worker
      myth and the notion that safety pays.

PMID- 24588038
TI  - Acceptability of interferon-gamma release assays among healthcare workers who
      receive routine employee tuberculosis testing.
AB  - BACKGROUND: Healthcare workers (HCWs) undergo annual testing for latent
      tuberculosis infection (LTBI). OBJECTIVE: Compare acceptability of tuberculin
      skin test (TST) and interferon-gamma release assay (IGRA) among HCWs. METHODS:
      HCWs at four medical centers in the US were administered an acceptability
      questionnaire including a brief objective description of both tests and eliciting
      attitudes regarding TST and IGRAs, confidence in results, and likelihood of
      taking LTBI treatment. RESULTS: Of 406 participants, 75% had never heard of
      IGRAs. IGRAs were preferred to TST. Belief in accuracy of hypothetical positive
      results of TST or IGRA and willingness to accept LTBI treatment were similar
      across tests. When presented with hypothetical discordant results, HCWs expressed
      more confidence in IGRAs. Perceived accuracy of results was the most important
      factor in test preferences. CONCLUSIONS: Although HCWs preferred and indicated
      more confidence in IGRAs, the likelihood that HCWs would believe LTBI diagnosis
      and initiate treatment based on positive results was similar for TST and IGRAs.

PMID- 24588041
TI  - Work-related infectious diseases among Korean workers compensated under the
      Industrial Accident Compensation Insurance Law, 2006-2011.
AB  - BACKGROUND: Korea has no surveillance system for work-related infectious disease.
      However, these diseases are compensated by the Korea Workers' Compensation &
      Welfare Service (KCOMWEL). OBJECTIVES: To understand the nature and distribution
      of compensated occupational infectious diseases in Korea. METHODS: We used the
      KCOMWEL electronic database to analyze compensated cases of work-related
      occupational infectious disease. We reviewed and confirmed diagnoses excluding
      denied claims, secondary infections, dermatoid diseases, duplicated cases and
      those with missing information. We calculated the distribution of work-related
      infectious disease in Korea by occupation, calendar year, gender, age, and
      employment duration, as well as the annual compensated claim rates (per million).
      RESULTS: We included 1,062 compensated cases of work-related infectious disease.
      The most common was scrub typhus (n = 567, 53.4%), followed by tuberculosis (n =
      227, 21.4%), viral hepatitis (n = 55, 5.2%), and viral influenza (n = 53, 5.0%).
      A sudden increase in scrub typhus was observed in 2009. Unskilled laborers,
      including short-term contract workers in public sectors, were most commonly
      affected by these diseases, followed by health care professionals. CONCLUSIONS:
      Workers employed in forestry care in the public sectors and in hospitals were
      most vulnerable to infections. Proper surveillance systems to monitor infectious
      diseases among vulnerable working groups and improved prevention measures are
      needed.

PMID- 24588042
TI  - The impact of occupational health service network and reporting system in Taiwan.
AB  - BACKGROUND: Underreporting occupational disease cases has been a long-standing
      problem in Taiwan, which hinders the progress in occupational health and safety.
      To address this problem, the government has founded the Network of Occupational
      Diseases and Injuries Service (NODIS) for occupational disease and injury
      services and established a new Internet-based reporting system. OBJECTIVES: The
      aims of this study are to analyze the possible influence of the NODIS, comprised
      of Center for Occupational Disease and Injury Services and their local network
      hospitals, on compensable occupational diseases and describe the distribution of
      occupational diseases across occupations and industries from 2005 to 2010 in
      Taiwan. METHODS: We conducted a secondary analysis of two datasets, including the
      NODIS reporting dataset and the National Labor Insurance scheme's dataset of
      compensated cases. For the NODIS dataset, demographics, disease distribution, and
      the time trends of occupational diseases were analyzed. The data of the Labor
      Insurance dataset was used to calculate the annual incidence of compensated
      cases. Furthermore, the annual incidence of reported occupational diseases from
      the NODIS was further compared with the annual incidence of compensable
      occupational diseases from the compensated dataset during the same period.
      RESULTS: After the establishment of the NODIS, the two annual incidence rates of
      reported and compensable occupational disease cases have increased by 1.2 and 2.0
      folds from 2007 to 2010, respectively. The reason for this increased reporting
      may be the implementation of the new government-funded Internet-based system. The
      reason for the increased compensable cases may be the increasing availability of
      hospitals and clinics to provide occupational health services. During the 2008
      2010 period, the most frequently reported occupational diseases were carpal
      tunnel syndrome, lumbar disc disorder, upper limb musculoskeletal disorders, and
      contact dermatitis. CONCLUSIONS: The new network and reporting system was
      successful in providing more occupational health services, providing more workers
      with compensation for occupational diseases, and reducing underreporting of
      occupational diseases. Therefore, the experience in Taiwan could serve as an
      example for other newly developed countries in a similar situation.

PMID- 24588043
TI  - A comparison of owner and expert evaluation of health and safety in small
      collision repair shops: a pilot study.
AB  - BACKGROUND: Workplace evaluation is one of the first steps in reducing the risk
      of injuries and illnesses, and is part of several programs that promote a
      participatory approach to occupational health among small business owners. The
      usefulness of written safety evaluations is contingent upon non-safety
      professionals obtaining accurate and reliable results. OBJECTIVES: The purpose of
      this study was to better understand auto body shop owners' ability to correctly
      identify occupational health and safety issues within their businesses. METHODS:
      In this study, 11 auto body shop owners used a 25-question checklist, developed
      specifically for this industry, to identify key safety and health problems. Owner
      results were compared with those of an industrial hygienist (IH) experienced in
      using the assessment form. RESULTS: The average number of safety problems
      identified by the IH was twice as large as the number identified by business
      owners (P = 0.02). The average percentage agreement of answers between owners and
      the IH was 81% (SD = 21%). Shop owners were more accurate in assessing the
      presence of written safety programs and records than the presence of unsafe work
      conditions. Overall, owners' sensitivity (ability to correctly identify a safety
      deficient item) was low (0.22). CONCLUSIONS: Collision shop owners had some
      difficulty correctly identifying many unsafe/non-compliant items or situations in
      their facility. Naive users' ability to correctly identify potentially hazardous
      situations--sensitivity--should be the metric of concern for the validity of
      safety assessments, and efforts should be directed at bringing this number as
      close to one as feasible.

PMID- 24588044
TI  - [Endoscopic sinus surgery for chronic rhinosinusitis].

PMID- 24588045
TI  - [Advice for elder patients with hearing loss].

PMID- 24588046
TI  - [Purpose of nerve preservation and reconstruction for neck dissection].

PMID- 24588047
TI  - [Radiation exposure- introduction-].

PMID- 24588049
TI  - [Radiation exposure- effect to human body caused by Fukushima nuclear power plant
      accident-].

PMID- 24588048
TI  - [Radiation exposure- basic knowledge, including occupational exposure-].

PMID- 24588050
TI  - [Radiation exposure- protection from internal exposure-].

PMID- 24588051
TI  - [Radiation exposure- risk of development of head and neck cancer caused by
      radiation exposure-].

PMID- 24588052
TI  - Reply from the Author.

PMID- 24588053
TI  - In reply.

PMID- 24588054
TI  - [My technique. Excision of the right S2 section].

PMID- 24588055
TI  - Interactive oxidation-reduction reaction for the in situ synthesis of graphene
      phenol formaldehyde composites with enhanced properties.
AB  - We report a facile in situ synthesis of reduced graphene oxide (RGO)-phenol
      formaldehyde (PF) composites with an interactive oxidation-reduction reaction. In
      this interactive chemical reaction, graphene oxide (GO) was reduced to RGO by
      phenol, and simultaneously phenol was oxidized to benzoquinone. The noncovalently
      adsorbed phenol on the RGO surface can not only serve as an effective reductant
      but also participate in the in situ polymerization and guide the formation of PF
      on the RGO surface. RGO-PF composites with different RGO contents were prepared
      successfully and further characterized with fluorescent spectroscopy, scanning
      electron microscopy, and transmission electron microscopy. The mechanical
      strength, electrical conductivity, thermal conductivity, and thermal resistance
      of the created RGO-PF were investigated. The results indicated that the
      dispersity of RGO in the PF matrix and the interfacial interaction between RGO
      and PF were improved greatly because of formation of the RGO-PF hybrid in the in
      situ synthesis. The homogeneous dispersion and in situ polymerization of RGO
      sheets help to enhance the thermal conductivity of RGO-PF composites from 0.1477
      to 0.3769 W m(-1) K(-1) and endow the composites with a good electrical
      conductivity. In addition, the well-dispersed RGO-PF composites are much more
      effective in improving their mechanical property and heat resistance. 

PMID- 24588056
TI  - Middle-down analysis of monoclonal antibodies with electron transfer dissociation
      orbitrap fourier transform mass spectrometry.
AB  - The rapid growth of approved biotherapeutics, e.g., monoclonal antibodies or
      immunoglobulins G (IgGs), demands improved techniques for their quality control.
      Traditionally, proteolysis-based bottom-up mass spectrometry (MS) has been
      employed. However, the long, multistep sample preparation protocols required for
      bottom-up MS are known to potentially introduce artifacts in the original sample.
      For this reason, a top-down MS approach would be preferable. The current
      performance of top-down MS of intact monoclonal IgGs, though, enables reaching
      only up to ~30% sequence coverage, with incomplete sequencing of the
      complementarity determining regions which are fundamental for IgG's antigen
      binding. Here, we describe a middle-down MS protocol based on the use of
      immunoglobulin G-degrading enzyme of Streptococcus pyogenes (IdeS), which is
      capable of digesting IgGs in only 30 min. After chemical reduction, the obtained
      ~25 kDa proteolytic fragments were analyzed by reversed phase liquid
      chromatography (LC) coupled online with an electron transfer dissociation (ETD)
      enabled hybrid Orbitrap Fourier transform mass spectrometer (Orbitrap Elite
      FTMS). Upon optimization of ETD and product ion transfer parameters, results show
      that up to ~50% sequence coverage for selected IgG fragments is reached in a
      single LC run and up to ~70% when data obtained by distinct LC-MS runs are
      averaged. Importantly, we demonstrate the potential of this middle-down approach
      in the identification of oxidized methionine residues. The described approach
      shows a particular potential for the analysis of IgG mixtures. 

PMID- 24588057
TI  - Direct solvation of glycoproteins by salts in spider silk glues enhances adhesion
      and helps to explain the evolution of modern spider orb webs.
AB  - The evolutionary origin of modern viscid silk orb webs from ancient cribellate
      silk ancestors is associated with a 95% increase in diversity of orb-weaving
      spiders, and their dominance as predators of flying insects, yet the transition's
      mechanistic basis is an evolutionary puzzle. Ancient cribellate silk is a dry
      adhesive that functions through van der Waals interactions. Viscid threads adhere
      more effectively than cribellate threads because of the high extensibility of
      their axial silk fibers, recruitment of multiple glue droplets, and firm adhesion
      of the viscid glue droplets. Viscid silk's extensibility is permitted by the
      glue's high water content, so that organic and inorganic salts present in viscid
      glue droplets play an essential role in contributing to adhesion by sequestering
      the atmospheric water that plasticizes the axial silk fibers. Here, we provide
      direct molecular and macro-scale evidence to show that salts also cause adhesion
      by directly solvating the glycoproteins, regardless of water content, thus
      imparting viscoelasticity and allowing the glue droplets to establish good
      contact. This "dual role" of salts, plasticizing the axial silk indirectly
      through water sequestration and directly solvating the glycoproteins, provides a
      crucial link to the evolutionary transition from cribellate silk to viscid silk.
      In addition, salts also provide a simple mechanism for adhering even at the
      extremes of relative humidity, a feat eluding most synthetic adhesives. 

PMID- 24588058
TI  - Use of pharmacokinetic modeling to assess antimicrobial pressure on enteric
      bacteria of beef cattle fed chlortetracycline for growth promotion, disease
      control, or treatment.
AB  - Antimicrobial use in food animals may increase antimicrobial resistance in their
      enteric bacteria that can be transferred to human microbiome. Over 70% of U.S.
      beef feedlots use non-ionophore in-feed antimicrobials for animal disease
      control, treatment, or growth promotion. The fraction of feedlots feeding
      chlortetracycline (CTC), mostly for disease control but also for treatment, has
      increased since the mid-1990s to present. Quantitative information on the
      antimicrobial selective pressure on the enteric bacteria of cattle fed CTC is
      lacking. Hence, the purpose of this study was to develop a deterministic
      mathematical model of the pharmacokinetics of ingested CTC in a beef steer and
      estimate the concentration of antimicrobially active (undegraded) CTC in the
      animal's large intestine. To evaluate the fit of the model to existing data, we
      also estimated the CTC concentrations in the central circulation, and fresh and
      aging manure from the steer. The model accounted for CTC abiotic degradation
      while in the gastrointestinal tract, absorption into the central circulation and
      tissues, biliary and renal excretion, and removal from the intestine by
      defecation. The model included an increase in the large intestine volume as the
      steer grew. We estimated that during CTC feeding to a 300-kg steer for growth
      promotion, the maximal drug concentration in the large intestine was 0.3 MUg/mL;
      during disease control it was 1.7 MUg/mL; and during treatment it was 31.5
      MUg/mL. The estimated CTC concentrations in the central circulation and the
      steer's manure agreed reasonably well with published data.

PMID- 24588060
TI  - Introduction to the special series featuring selected papers from the inaugural
      meeting of the North American Society for the Study of Personality Disorders.
AB  - In this article the inaugural meeting of the North American Society for the Study
      of Personality Disorders (NASSPD) is described against the backdrop of some
      exciting themes in contemporary personality disorder theory, research, and
      treatment. Commentary is provided for 7 papers included in this issue as
      representative of the talks delivered at the NASSPD meeting which highlight these
      broad themes.

PMID- 24588059
TI  - Macrocytosis, macrocytic anemia, and genetic polymorphisms of alcohol
      dehydrogenase-1B and aldehyde dehydrogenase-2 in Japanese alcoholic men.
AB  - BACKGROUND: Oxidation of ethanol by alcohol dehydrogenase (ADH) generates
      acetaldehyde (AcH), which is converted to acetate by aldehyde dehydrogenase-2
      (ALDH2). Roughly 40% of East Asians are ALDH2-deficient due to an inactive enzyme
      encoded by the ALDH2*2 allele. ALDH2-deficient individuals have a dramatically
      elevated risk of esophageal cancer from alcohol consumption. METHODS: We
      investigated the relationship between ALDH2*2, ADH1B*2 (encoding a highly active
      ADH) and erythrocyte abnormalities, in a population of Japanese alcoholic men (N
      = 1,238). RESULTS: Macrocytosis (mean corpuscular volume [MCV] >=100 fl) and
      macrocytic anemia (MCV >=100 fl and hemoglobin <13.5 g/dl) were found in 62.4 and
      24.1% of the subjects, respectively. Age-adjusted daily alcohol consumption did
      not differ according to ADH1B and ALDH2 genotypes. However, macrocytosis and
      macrocytic anemia were strongly associated with the ALDH2*1/*2 genotype
      multivariate odds ratios (ORs; 95% confidence interval [CI] = 2.85 [1.95 to 4.18]
      and 3.68 [2.64 to 5.15], respectively, versus ALDH2*1/*1). In comparison with the
      ADH1B*1/*1 and ALDH2*1/*1 genotype combination, the ADH1B*1/*1 and ALDH2*1/*2
      genotype combination and the ADH1B*2 allele and ALDH2*1/*2 genotype combination
      increased stepwise the ORs (95% CI) for macrocytosis (1.65 [0.92 to 2.94] and
      4.07 [2.33 to 7.11], respectively, p for difference in OR = 0.015) and macrocytic
      anemia (2.80 [1.52 to 5.15] and 5.32 [3.29 to 8.62], respectively, p for
      difference in OR = 0.045). Genotype effects were more prominent on the risks of
      the more advanced erythrocyte abnormalities. Older age, cigarette smoking, and
      low body mass index independently increased the risks of the erythrocyte
      abnormalities. Consumption of beer, which contains folate, decreased the risks,
      whereas consumption of alcoholic beverages lacking folate did not. CONCLUSIONS:
      These results suggest that the erythrocyte abnormalities in alcoholics are
      attributable to high AcH exposure as well as to nutritional deficiencies and may
      be prevented by folate.

PMID- 24588063
TI  - An 11-item measure to assess borderline traits in adolescents: refinement of the
      BPFSC using IRT.
AB  - Despite historical concerns about the validity of the construct of borderline
      personality disorder (BPD) in adolescence, there is now general consensus that
      BPD in adolescence constitutes a valid and reliable diagnosis. Yet the
      development and refinement of measures to assess borderline traits in adolescents
      is in its infancy. Moreover, brief and easy-to-administer measures of borderline
      traits for use in large-scale studies do not exist. The aim of the current study
      was to evaluate the Borderline Personality Features Scale for Children (BPFSC;
      Crick, Murray-Close, & Woods, 2005) and develop a short version of the BPFSC
      through the use of item response theory (IRT) methods. BPFSC data from a
      community sample of 964 adolescents (mean age = 15.1 years, SD = .79; 55.9%
      female) were used to examine the factor structure of the BPFSC. The hypothesized
      4-factor structure was not supported. The unidimensional IRT analysis showed
      instances of local dependence among item pairs and item responses that were not
      strongly related to the underlying construct. As a consequence, items were
      eliminated, creating a unidimensional 11-item brief BPFSC (the BPFSC-11). Next,
      evidence of construct validity of scores based on the shortened version was
      evaluated using a different sample of 371 inpatient adolescents. We demonstrated
      similar indices of construct validity as observed for the BPFSC total score with
      the BPFSC-11 scores and found evidence for good criterion validity. Use of the
      BPFSC-11 in clinical settings will reduce the burden on respondents without loss
      of information.

PMID- 24588061
TI  - On the structure of personality disorder traits: conjoint analyses of the CAT-PD,
      PID-5, and NEO-PI-3 trait models.
AB  - The current study examines the relations among contemporary models of
      pathological and normal range personality traits. Specifically, we report on (a)
      conjoint exploratory factor analyses of the Computerized Adaptive Test of
      Personality Disorder static form (CAT-PD-SF) with the Personality Inventory for
      the Diagnostic and Statistical Manual of Mental Disorders, fifth edition and NEO
      Personality Inventory-3 First Half, and (b) unfolding hierarchical analyses of
      the three measures in a large general psychiatric outpatient sample (n = 628; 64%
      Female). A five-factor solution provided conceptually coherent alignment among
      the CAT-PD-SF, PID-5, and NEO-PI-3FH scales. Hierarchical solutions suggested
      that higher-order factors bear strong resemblance to dimensions that emerge from
      structural models of psychopathology (e.g., Internalizing and Externalizing
      spectra). These results demonstrate that the CAT-PD-SF adheres to the consensual
      structure of broad trait domains at the five-factor level. Additionally, patterns
      of scale loadings further inform questions of structure and bipolarity of facet
      and domain level constructs. Finally, hierarchical analyses strengthen the
      argument for using broad dimensions that span normative and pathological
      functioning to scaffold a quantitatively derived phenotypic structure of
      psychopathology to orient future research on explanatory, etiological, and
      maintenance mechanisms.

PMID- 24588062
TI  - Three-pronged assessment and diagnosis of personality disorder and its
      consequences: personality functioning, pathological traits, and psychosocial
      disability.
AB  - The alternative dimensional model of personality disorder (PD) in the Diagnostic
      and Statistical Manual of Mental Disorders, 5th edition (DSM-5; American
      Psychiatric Association, 2013), Section III, has two main criteria: impairment in
      personality functioning and one or more pathological personality traits. The
      former is defined as disturbances in self-functioning (viz., identity, self
      direction), and/or interpersonal functioning (viz., empathy, intimacy).
      Distinguishing personality functioning and traits is important conceptually,
      because simply having extreme traits is not necessarily pathological. However,
      adding personality functioning to PD diagnosis represents an empirical challenge,
      because the constructs overlap conceptually. Further, there is debate regarding
      whether diagnosis of mental disorder requires either distress or disability,
      concepts that also overlap with maladaptive-range personality traits and
      personality dysfunction. We investigated interrelations among these constructs
      using multiple self-report measures of each domain in a mixed community-patient
      sample (N = 402). We examined the structures of functioning (psychosocial
      disability and personality) and personality traits, first independently, then
      jointly. The disability/functioning measures yielded the 3 dimensions we have
      found previously (Ro & Clark, 2013). Trait measures had a hierarchical structure
      which, at the 5-factor level, reflected neuroticism/negative affectivity (N/NA),
      (low) sociability, disinhibition, (dis)agreeableness, and rigid goal engagement.
      When all measures were cofactored, a hierarchical structure again emerged which,
      at the 5-factor level, included (a) internalizing (N/NA and self-pathology vs.
      quality-of-life/satisfaction); (b) externalizing (social/interpersonal
      dysfunction, low sociability, and disagreeableness); (c) disinhibition; (d) poor
      basic functioning; and (e) rigid goal engagement. Results are discussed in terms
      of developing an integrated PD diagnostic model.

PMID- 24588064
TI  - Perceptual biases in facial emotion recognition in borderline personality
      disorder.
AB  - Individuals with borderline personality disorder (BPD) have biases in facial
      emotion recognition, which may underlie many of the core features of this
      disorder. Although they are known to misperceive specific prototypic expressions
      of emotion (i.e., those displayed at full emotional intensity), patients with
      this disorder may also show biases in their perceptions of emotions that are
      expressed at lower levels of emotional intensity. Females with BPD (n = 31) and
      IQ- and demographically matched nonpsychiatric controls (n = 28) completed a task
      assessing the recognition of neutral as well as happy and sad facial expressions
      at mild, moderate, and prototypic emotional intensities. Whereas patients with
      BPD were more likely than controls to ascribe an emotion to a neutral facial
      expression, they did not consistently attribute a more negative or positive
      valence to these faces as compared with controls. Patients were also more likely
      to perceive mildly sad facial expressions as more intensely sad, and this finding
      could not be attributed to depressed mood. The results of this study suggest that
      perceptions of even subtle expressions of negative affect in faces may be
      subjectively magnified by individuals with BPD, although there was no consistent
      evidence for a negative perceptual bias for faces displaying a neutral
      expression. These biases in facial emotion perception for patients with BPD may
      contribute to difficulties understanding others' emotional states and to problems
      engaging effectively in social interactions.

PMID- 24588065
TI  - Affective behavior during mother-daughter conflict and borderline personality
      disorder severity across adolescence.
AB  - Developmental theories of borderline personality disorder (BPD) posit that
      transactions between child characteristics and adverse environments, especially
      those in the context of the parent-child relationship, shape and maintain
      symptoms of the disorder over time. However, very little empirical work has
      investigated the role of parenting and parent-child transactions that may predict
      BPD severity over time. We examined maternal and dyadic affective behaviors
      during a mother-adolescent conflict discussion task as predictors of the course
      of BPD severity scores across 3 years in a diverse, at-risk sample of girls (N =
      74) oversampled for affective instability and their biological mothers.
      Adolescent girls completed a structured conflict discussion task with their
      mothers at age 16. Girls' self-reported BPD severity scores were assessed
      annually from ages 15 to 17. Mother-adolescent interactions were coded using a
      global rating system of maternal and dyadic affective behaviors. Results from
      multilevel linear mixed models indicated that positive maternal affective
      behavior (i.e., supportive/validating behavior, communication skills, autonomy
      promoting behavior, and positive affect) and positive dyadic affective behaviors
      (i.e., satisfaction and positive escalation) were associated with decreases in
      girls' BPD severity scores over time. Dyadic negative escalation was associated
      with higher overall levels of BPD severity scores, but negative maternal
      affective behavior (i.e., negative affect, dominance, conflict, and denial) was
      not. These findings suggest that the mother-daughter context is an important
      protective factor in shaping the course of BPD severity scores during adolescence
      and may be valuable in assessment, intervention, and prevention efforts.

PMID- 24588067
TI  - Approaches to psychotherapy for borderline personality: demonstrations by four
      master clinicians.
AB  - Several efficacious therapies for borderline personality disorder (BPD) now exist
      despite longstanding skepticism in the field regarding amenability to treatment.
      In this article, 4 master clinicians describe a brief interaction with an actress
      playing the part of a patient with BPD that occurred at the First Annual Meeting
      of the North American Society for the Study of Personality Disorders in Boston,
      April 2013. The approaches include dialectical behavior therapy, transference
      focused psychotherapy, mentalization based therapy, and good psychiatric
      management. The paper concludes with a discussion of what these approaches have
      in common, how they differ, and future directions for the treatment of BPD.

PMID- 24588066
TI  - Predictors of treatment response to an adjunctive emotion regulation group
      therapy for deliberate self-harm among women with borderline personality
      disorder.
AB  - Despite evidence for the efficacy of several treatments for deliberate self-harm
      (DSH) within borderline personality disorder (BPD), predictors of response to
      these treatments remain unknown. This study examined baseline demographic,
      clinical, and diagnostic predictors of treatment response to an adjunctive
      emotion regulation group therapy (ERGT) for DSH among women with BPD. A recent
      RCT provided evidence for the efficacy of this ERGT (relative to a treatment-as
      usual only waitlist condition). Participants in this study include the full
      intent-to-treat sample who began ERGT (across treatment and waitlist conditions;
      n = 51). Baseline diagnostic and clinical data were collected at the initial
      assessment, and outcome measures of DSH and self-destructive behaviors, emotion
      dysregulation/avoidance, and BPD symptoms (among others) were administered at
      pretreatment, posttreatment, and 3- and 9-months posttreatment. Notably, both
      demographic variables and characteristics of participants' ongoing therapy in the
      community had minimal impact on treatment response. However, several indicators
      of greater severity in domains relevant to this ERGT (i.e., baseline emotion
      dysregulation and BPD criteria, lifetime and recent DSH, and past-year
      hospitalization and suicide attempts) predicted better responses during treatment
      and follow-up across the primary targets of treatment. Likewise, several co
      occurring disorders (i.e., social phobia, panic disorder, and a cluster B
      personality disorder) predicted greater improvements in BPD symptoms during
      treatment or follow-up. Finally, although co-occurring generalized anxiety
      disorder, posttraumatic stress disorder, and cluster A and C personality
      disorders were associated with poorer treatment response during follow-up, most
      of these effects reflected a lack of continued improvements during this period
      (vs. worsening of symptoms).

PMID- 24588068
TI  - Stable Ni nanoparticle-reduced graphene oxide composites for the reduction of
      highly toxic aqueous Cr(VI) at room temperature.
AB  - Inherent properties of graphene can be experienced by integrating it with
      different nanomaterials to form unique composite materials. Decorating the
      surface of graphene sheets with nanoparticles (NPs) is one of the recent
      approaches taken up by scientists all over the world. This article describes a
      simple synthesis route to preparing stable Ni NP-reduced graphene oxide (Ni-RGO)
      composite material. The otherwise unstable bare Ni NPs are stabilized when
      embedded in the RGO sheets. This synthesized composite material has a potential
      application in the formic acid-induced reduction of highly toxic aqueous Cr(VI)
      at room temperature (25  degrees C). The reduction of dichromate using formic
      acid as a reducing agent is a well-known redox reaction. However, the rate of the
      reaction is very slow at room temperature, which can be enhanced very
      significantly in the presence of Ni-RGO by introducing an intermediate redox step
      with formic acid. The Ni-RGO composite material is an easy to prepare, cheap,
      stable, reusable material that has the potential to replace costly Pd NPs used in
      this context. Ni-RGO is also found to be very active in enhancing the rate of
      reduction of other metal ions in the presence of formic acid at room temperature.

PMID- 24588069
TI  - Referrer and service provider beliefs and attitudes towards rehabilitation in the
      home; factors related to utilisation of Early Supported Discharge.
AB  - PURPOSE: To investigate the attitudes and beliefs held by referrers and service
      providers of an Australian Early Supported Discharge (ESD) service called
      "Rehabilitation in the Home" (RITH); with particular consideration of factors
      that may influence referral to RITH. METHODS: A cross-sectional online survey
      based on the Theory of Planned Behaviour was undertaken. RESULTS: There were 113
      respondents; 90 referrers and 23 service providers. Referrers and RITH staff had
      a moderately favourable attitude towards RITH. The majority of referrers, and, to
      a greater degree, RITH staff members, understood and appreciated the advantages
      ascribed to ESD. However, views varied with regard to some of the factors upon
      which the decision to refer to RITH rests. Two-fifths of referrers did not think
      that RITH provided hospital equivalent therapy intensity and over one-fifth of
      referrers had concerns about the capability of the RITH service to provide
      specialist stroke rehabilitation. Opinion of RITH staff was also varied on these
      topics. CONCLUSIONS: This study provides evidence that there was a level of
      uncertainty amongst referrers and RITH service providers regarding issues
      directly and indirectly related to patient eligibility and RITH service
      capability. This uncertainty needs to be explored in future research.
      IMPLICATIONS FOR REHABILITATION: Differences in views held by referrers and ESD
      service providers were identified in this study that could lead to
      inconsistencies in patient selection for, and under-utilization of, ESD services.
      Improved communication between referrers and ESD service providers, for instance
      attendance of RITH staff at inpatient team meetings, could ameliorate some of
      these misconceptions. On-going education of referrers about service capability is
      essential to ensure timely transfer of appropriate clients to ESD services.

PMID- 24588070
TI  - Strategies that facilitate participation in family activities of children and
      adolescents with profound intellectual and multiple disabilities: parents' and
      personal assistants' experiences.
AB  - PURPOSE: Participation throughout one's life plays a significant role for
      development and emotional well-being. For this reason, there is a need to
      identify ways to facilitate participation in family activities for children and
      adolescents with profound intellectual and multiple disabilities (PIMD). METHODS:
      The study design was qualitative and explorative, based on semi structured
      interviews with 11 parents and 9 personal assistants of children with PIMD.
      RESULTS: The interviews revealed participation-facilitating strategies relating
      to the children's/adolescent's proximal environment, such as "Availability and
      acceptability of the activity", "Good knowledge about the child" and a "A
      positive attitude of people close to the child", as well as strategies related to
      the children/adolescents themselves: "Sense of belonging", "Possible for the
      child/adolescent to understand", "Opportunities to influence" and "Feeling of
      being needed". CONCLUSIONS: Children and adolescents with PIMD are dependent on
      support obtained through their environment. The identified strategies,
      individually adapted through awareness and knowledge by the parents and the
      personal assistants, provide important evidence to assist our understanding in
      gaining understanding about how to improve participation in family activities of
      children and adolescents with PIMD. IMPLICATIONS FOR REHABILITATION:
      Participation-facilitating strategies related to the child/adolescent and his or
      her proximal environments are identified to improve participation in children and
      adolescents with profound intellectual and multiple disabilities (PIMD). Examples
      of strategies for the child's/adolescents' proximal environment include "good
      knowledge about the child/adolescent", and, for the child/adolescent, include
      creating "sense of belonging" and "opportunities to influence". Identifying and
      making these strategies explicit may assist in enhancing the participation of
      children and adolescents with PIMD in family activities. People in the
      child's/adolescent's proximal environment need to set the scene for
      participation.

PMID- 24588071
TI  - Domestic accidents and multiple sclerosis: an exploratory study of occurrence and
      possible causes.
AB  - PURPOSE: Domestic accidents are widespread, but no data are available on their
      occurrence in pathological populations such as patients with multiple sclerosis
      (MS). Aim was to investigate domestic habits and occurrence of different types of
      domestic accidents and near falls in a sample of MS patients compared with
      healthy controls and to determine whether patients' domestic accidents are linked
      to any disease characteristics. METHOD: Descriptive survey of 50 patients and 50
      healthy controls. Participants were administered an ad-hoc questionnaire to
      collect data on domestic habits and accidents they had in the past 2 months.
      Their physical and neuropsychological functioning, mood and fatigue were also
      assessed. RESULTS: Results showed that patients spend most of their time at home
      with caregivers. No differences emerged for total number of domestic accident
      types, but there were differences in bumps and near falls. The latter seem to be
      linked to patients' walking ability and to bowel/bladder functioning and the
      former to reasoning ability and fatigue. CONCLUSIONS: This study provides the
      first data on the occurrence of domestic accidents and possible causes in MS
      patients. It encourages further studies on the topic, with the final goal of
      designing preventive and rehabilitation strategies.

PMID- 24588072
TI  - Does water content or flow rate control colloid transport in unsaturated porous
      media?
AB  - Mobile colloids can play an important role in contaminant transport in soils:
      many contaminants exist in colloidal form, and colloids can facilitate transport
      of otherwise immobile contaminants. In unsaturated soils, colloid transport is,
      among other factors, affected by water content and flow rate. Our objective was
      to determine whether water content or flow rate is more important for colloid
      transport. We passed negatively charged polystyrene colloids (220 nm diameter)
      through unsaturated sand-filled columns under steady-state flow at different
      water contents (effective water saturations Se ranging from 0.1 to 1.0, with Se =
      (theta - thetar)/(thetas - thetar)) and flow rates (pore water velocities v of 5
      and 10 cm/min). Water content was the dominant factor in our experiments. Colloid
      transport decreased with decreasing water content, and below a critical water
      content (Se < 0.1), colloid transport was inhibited, and colloids were strained
      in water films. Pendular ring and water film thickness calculations indicated
      that colloids can move only when pendular rings are interconnected. The flow rate
      affected retention of colloids in the secondary energy minimum, with less
      colloids being trapped when the flow rate increased. These results confirm the
      importance of both water content and flow rate for colloid transport in
      unsaturated porous media and highlight the dominant role of water content. 

PMID- 24588073
TI  - Identification and optimization of new dual inhibitors of B-Raf and epidermal
      growth factor receptor kinases for overcoming resistance against vemurafenib.
AB  - Epidermal growth factor receptor (EGFR) amplification has been demonstrated to be
      critical for the inherent and/or acquired resistance against current B-Raf(V600E)
      inhibitor therapy for melanoma and colorectal cancer patients. We describe the
      discovery and structure-activity relationship study of a series of 1H
      pyrazolo[3,4-b]pyridine-5-carboxamide analogues as novel dual inhibitors of EGFR
      and B-Raf(V600E) mutant. One of the most promising compounds, 6a, potently
      inhibited both of the kinases with IC50 values of 8.0 and 51 nM, respectively.
      The compound also strongly suppressed the proliferation of a panel of intrinsic
      and acquired resistant melanoma and/or colorectal cancer cells harboring
      overexpressed EGFR with submicromolar IC50 values. Further mechanism
      investigation revealed that 6a could sustainably inhibit the activation of the
      MAPK path way in the resistant SK-MEL-28 PR30 melanoma cancer cells and WiDr
      colorectal cancer cells with EGFR amplification. Our results support the
      hypothesis that the EGFR/B-Raf(V600E) dual inhibition might be a tractable
      strategy to overcome the intrinsic and acquired resistance of melanoma and/or
      colorectal cancers against the current B-Raf(V600E) inhibitor therapy. 

PMID- 24588074
TI  - Prescribing of psychiatric medication to bereaved parents following
      perinatal/neonatal death: an observational study.
AB  - To examine psychiatric prescribing in response to perinatal/neonatal death, we
      analyzed data from a cross-sectional survey of 235 bereaved parents participating
      in an online support community. Of the 88 respondents prescribed medication,
      antidepressants were most common (n = 70, 79.5%) followed by
      benzodiazepines/sleep aids (n = 18, 20.5%). Many prescriptions were written
      shortly after the death (32.2% within 48 hr, 43.7% within a week, and 74.7%
      within a month). Obstetrician/gynecologists wrote most prescriptions given
      shortly after loss. Most respondents prescribed antidepressants took them long
      term. This sample is select, but these data raise disturbing questions about
      prescribing practices for grieving parents.

PMID- 24588075
TI  - Diagnostic accuracy of noninvasive markers of liver fibrosis in patients with
      psoriasis taking methotrexate: a systematic review and meta-analysis.
AB  - People with psoriasis taking methotrexate may be at increased risk of developing
      liver fibrosis compared with the general population. Noninvasive methods of
      detecting fibrosis have been widely adopted but their clinical utility is
      uncertain. To evaluate the diagnostic accuracy of noninvasive methods to detect
      fibrosis compared with liver biopsy (reference standard) in people with psoriasis
      taking methotrexate. A systematic search using Ovid/Medline, Embase, Cumulative
      Index to Nursing and Allied Health Literature, the Cochrane Library and Clinical
      Trials Register was performed. Diagnostic cohorts or case-control studies of
      adults taking or being considered for methotrexate therapy were considered. Study
      quality was evaluated using the Quality Assessment tool for Diagnostic Accuracy
      Studies (QUADAS-2). Pooled data analysis was performed using RevMan 5.1. Bayesian
      meta-analysis was conducted using Markov chain Monte Carlo simulation. Seventeen
      studies were included. Sensitivity and specificity were 38% and 83% for standard
      liver function tests (LFTs), 74% and 77% for procollagen-3 N-terminal peptide
      (P3NP), 60% and 80% for Fibroscan((r)) (Echosens, France, www.echosens.com), and
      55% and 49% for ultrasound. Confidence in these results is limited owing to low
      quality data; old, small studies displayed significant selection bias and
      significant variation in the prevalence of fibrosis. No studies were identified
      evaluating recently developed markers. The clinical utility of LFTs, P3NP and
      liver ultrasound is poor. Therefore if these tests are used in isolation, a
      significant proportion of patients with liver fibrosis may remain unidentified.
      Larger prospective studies are required in this population to validate newer non
      invasive methods. 

PMID- 24588077
TI  - C12 helices in long hybrid (alphagamma)n peptides composed entirely of
      unconstrained residues with proteinogenic side chains.
AB  - Unconstrained gamma(4) amino acid residues derived by homologation of
      proteinogenic amino acids facilitate helical folding in hybrid (alphagamma)n
      sequences. The C12 helical conformation for the decapeptide, Boc-[Leu
      gamma(4)(R)Val]5-OMe, is established in crystals by X-ray diffraction. A regular
      C12 helix is demonstrated by NMR studies of the 18 residue peptide, Boc-[Leu
      gamma(4)(R)Val]9-OMe, and a designed 16 residue (alphagamma)n peptide,
      incorporating variable side chains. Unconstrained (alphagamma)n peptides show an
      unexpectedly high propensity for helical folding in long polypeptide sequences. 

PMID- 24588078
TI  - Perspectives on condom breakage: a qualitative study of female sex workers in
      Bangalore, India.
AB  - A qualitative study was conducted to obtain a detailed understanding of two key
      determinants of condom breakage - 'rough sex' and poor condom fit - identified in
      a recent telephone survey of female sex workers, in Bangalore, India. Transcripts
      from six focus-group discussions involving 35 female sex workers who reported
      condom breakage during the telephone survey were analysed. Rough sex in different
      forms, from over-exuberance to violence, was often described by sex workers as a
      result of clients' inebriation and use of sexual stimulants, which, they report,
      cause tumescence, excessive thrusting and sex that lasts longer than usual,
      thereby increasing the risk of condom breakage. Condom breakage in this setting
      is the result of a complex set of social situations involving client behaviours
      and power dynamics that has the potential to put the health and personal lives of
      sex workers at risk. These findings and their implications for programme
      development are discussed. 

PMID- 24588076
TI  - Knockout mice reveal key roles for claudin 18 in alveolar barrier properties and
      fluid homeostasis.
AB  - Claudin proteins are major constituents of epithelial and endothelial tight
      junctions (TJs) that regulate paracellular permeability to ions and solutes.
      Claudin 18, a member of the large claudin family, is highly expressed in lung
      alveolar epithelium. To elucidate the role of claudin 18 in alveolar epithelial
      barrier function, we generated claudin 18 knockout (C18 KO) mice. C18 KO mice
      exhibited increased solute permeability and alveolar fluid clearance (AFC)
      compared with wild-type control mice. Increased AFC in C18 KO mice was associated
      with increased beta-adrenergic receptor signaling together with activation of
      cystic fibrosis transmembrane conductance regulator, higher epithelial sodium
      channel, and Na-K-ATPase (Na pump) activity and increased Na-K-ATPase beta1
      subunit expression. Consistent with in vivo findings, C18 KO alveolar epithelial
      cell (AEC) monolayers exhibited lower transepithelial electrical resistance and
      increased solute and ion permeability with unchanged ion selectivity. Claudin 3
      and claudin 4 expression was markedly increased in C18 KO mice, whereas claudin 5
      expression was unchanged and occludin significantly decreased. Microarray
      analysis revealed changes in cytoskeleton-associated gene expression in C18 KO
      mice, consistent with observed F-actin cytoskeletal rearrangement in AEC
      monolayers. These findings demonstrate a crucial nonredundant role for claudin 18
      in the regulation of alveolar epithelial TJ composition and permeability
      properties. Increased AFC in C18 KO mice identifies a role for claudin 18 in
      alveolar fluid homeostasis beyond its direct contributions to barrier properties
      that may, at least in part, compensate for increased permeability. 

PMID- 24588079
TI  - Clinical examination and pulse oximetry as screening for congenital heart disease
      in low-risk newborn.
AB  - OBJECTIVE: To assess sensitivity, specificity, positive predictive value and
      negative predictive value of the cardiovascular physical examination (CPE) and of
      pulse oximetry in screening for congenital heart diseases (CHD) in asymptomatic
      newborn when prenatal ultrasound evaluation is negative for structural cardiac
      abnormalities. METHODS: In this observational cohort study, 5750 asymptomatic
      newborns, admitted to nursery in a period of 2 years, underwent to CPE and
      determination of arterial oxygen saturation by pulse oxymetry between 48th and
      72nd h of life. RESULTS: Two hundred and ninty-eight newborns presented a
      suspected CPE; in 70% of cases, we found a transitional alteration and in only
      17% of cases, the echocardiography examination performed for suspected CPE were
      completely negative. Three newborns were positive to pulse oximetry screening
      test but negative at CPE. After discharge, one case of critical CHD was
      diagnosed. CONCLUSIONS: An accurate CPE performed by trained and experienced
      pediatricians is indicative of important cardiac structural alteration in more
      than 25%. The association of CPE and pulse oximetry allows to further improve the
      diagnostic accuracy.

PMID- 24588080
TI  - Metabolic syndrome and subclinical carotid atherosclerosis among Chinese elderly
      people living in a rural community.
AB  - BACKGROUND: The relationship between the metabolic syndrome and subclinical
      atherosclerosis among elderly people remains controversial. We seek to
      investigate the associations of metabolic syndrome and its components with
      subclinical carotid atherosclerosis in older people living in rural China.
      METHODS: This cross-sectional study included 911 participants (age >=60 years,
      59.4% women) of the community-based Confucius Hometown Aging Project in Shandong,
      China, who were free of clinical cardiovascular disease. In 2010-2011, data were
      collected through interviews, clinical examinations, and laboratory tests.
      Carotid intima media thickness (cIMT) and carotid artery plaque were assessed
      using ultrasonography. Metabolic syndrome was defined by four sets of criteria.
      Data were analyzed with multiple general linear and logistic regression models.
      RESULTS: Carotid plaque was detected in 514 (56.4%) persons. Depending on the
      defining criteria, prevalence of metabolic syndrome ranged from 30.6% to 56.9%.
      Hypertension, elevated blood pressure (>=130/85 mmHg), diabetes/prediabetes, and
      high fasting plasma glucose (>=5.6 mmol/L) were significantly associated with an
      increased likelihood of carotid plaque, whereas an increased cIMT was associated
      with elevated blood pressure and hypertension (P<0.05). Obesity, high
      triglycerides, and dyslipidemia were not associated with carotid artery plaque or
      cIMT. The significant association of metabolic syndrome with an increased
      likelihood of carotid plaque disappeared when elevated blood pressure and high
      plasma glucose were added to the models. Metabolic syndrome was not associated
      with cIMT. CONCLUSIONS: Metabolic syndrome is associated with subclinical carotid
      plaque among Chinese elderly people, driven primarily by elevated blood pressure
      and hyperglycemia. Older adults with metabolic syndrome, especially those with
      high blood pressure and hyperglycemia, may benefit from evaluation for
      subclinical atherosclerosis.

PMID- 24588083
TI  - Identification of a novel Kmod -1 allele encoded by 977C>T (Pro326Leu).

PMID- 24588081
TI  - Collagen-induced arthritis: severity and immune response attenuation using
      multivalent N-acetyl glucosamine.
AB  - Rheumatoid arthritis is an autoimmunity leading to considerable impairment of
      quality of life. N-acetyl glucosamine (GlcNAc) has been described previously as a
      potent modulator of experimental arthritis in animal models and is used for
      osteoarthritis treatment in humans, praised for its lack of adverse effects. In
      this study we present a comprehensive immunological analysis of multivalent
      GlcNAc-terminated glycoconjugate (GC) application in the treatment of collagen
      induced arthritis (CIA) and its clinical outcome. We used immunohistochemistry
      and FACS to describe conditions on the inflammation site. Systemic and clinical
      effects were evaluated by FACS, cytotoxicity assay, ELISA, cytometric bead array
      (CBA), RT-PCR and clinical scoring. We found reduced inflammatory infiltration,
      NKG2D expression on NK and suppression of T, B and antigen-presenting cells (APC)
      in the synovia. On the systemic level, GCs prevented the activation of monocyte-
      and B cell-derived APCs, the rise of TNF-alpha and IFN-gamma levels, and
      subsequent type II collagen (CII)-specific IgG2a formation. Moreover, we detected
      an increase of anti-inflammatory IL-4 mRNA in the spleen. Similar to the synovia,
      the GCs caused a significant reduction of NKG2D-expressing NK cells in the spleen
      without influencing their lytic function. GCs effectively postponed the onset of
      arthritic symptoms, reduced their severity and in 18% (GN8P) and 31% (GN4C) of
      the cases completely prevented their appearance. Our data prove that GlcNAc
      glycoconjugates prevent the inflammatory response, involving proinflammatory
      cytokine rise, APC activation and NKG2D expression, leading to the attenuation of
      clinical symptoms. These results support the glycobiological approach to the
      treatment of collagen-induced arthritis/rheumatoid arthritis (CIA/RA) as a way of
      bringing new prospects for more effective therapeutic interventions. 

PMID- 24588082
TI  - TLR4 contributes to the host response to Klebsiella intraocular infection.
AB  - PURPOSE/AIM: Klebsiella pneumoniae causes a blinding infection called endogenous
      endophthalmitis. The role of innate immune recognition of K. pneumoniae in the
      eye during infection is not known. We hypothesized that intraocular recognition
      of K. pneumoniae was mediated by Toll-like receptor (TLR)-4 and may be dependent
      on MagA-regulated hypermucoviscosity. MATERIALS AND METHODS: Experimental
      endophthalmitis was induced in C57BL/6J or TLR4(-/-) mice by intravitreal
      injection of 100 CFU of wild type or DeltamagA K. pneumoniae. Infection and
      inflammation were quantified by determining viable K. pneumoniae per eye, retinal
      responses via electroretinography, myeloperoxidase activity of infiltrating
      neutrophils and the proinflammatory cytokine and chemokine response. RESULTS:
      C57BL/6J and TLR4(-/-) mice could not control intraocular wild-type K. pneumoniae
      growth. TLR4(-/-) mice were less able than C57BL/6J to control the intraocular
      growth of DeltamagA K. pneumoniae. Retinal function testing suggested that
      infection with DeltamagA K. pneumoniae resulted in less retinal function loss.
      There was a TLR4-dependent delay in initial neutrophil recruitment, regardless of
      the infecting organism. The proinflammatory cytokine/chemokine data supported
      these results. These findings were not due to an inability of TLR4(-/-)
      neutrophils to recognize or kill K. pneumoniae. CONCLUSIONS: These studies
      suggest that TLR4 is important in the early intraocular recognition and host
      response to K. pneumoniae. However, the role of MagA in TLR4-mediated intraocular
      recognition and subsequent inflammation is less clear.

PMID- 24588084
TI  - Multisystemic Langerhans cell histiocytosis mimicking diffuse neonatal
      hemangiomatosis.
AB  - We report the first case of multisystemic Langerhans cell histiocytes mimicking
      diffuse neonatal hemangiomatosis clinically. This has been described in patients
      with congenital self-healing reticulohistiocytosis but not in patients with
      acute, disseminated, and multisystemic disease. In our experience, dermoscopic
      findings did not help to diagnose the condition. 

PMID- 24588085
TI  - Two-year-olds' understanding of self-symbols.
AB  - This study investigated 48 2.5-year-olds' ability to map from their own body to a
      two-dimensional self-representation and also examined relations between parents'
      talk about body representations and their children's understanding of self
      symbols. Children participated in two dual-representation tasks in which they
      were asked to match body parts between a symbol and its referent. In one task,
      they used a self-symbol and in the other they used a symbol for a doll.
      Participants were also read a book about body parts by a parent. As a group,
      children found the self-symbol task more difficult than the doll-task; however,
      those whose parents explicitly pointed out the relation between their children's
      bodies and the symbols in the book performed better on the self-symbol task. The
      findings demonstrate that 2-year-old children have difficulty comprehending a
      self-symbol, even when it is two-dimensional and approximately the same size as
      them, and suggest that parents' talk about self-symbols may facilitate their
      understanding. 

PMID- 24588086
TI  - Interleukin-6, but not C-reactive protein, predicts the occurrence of
      cardiovascular events after drug-eluting stent for unstable angina.
AB  - BACKGROUND: Evidences concerning the predictive value of baseline inflammatory
      biomarkers after drug-eluting stent (DES) placement are controversial, mainly
      because the use of statin was not precisely defined. OBJECTIVES: The aim was to
      compare the differences between interleukin (IL)-6 and high-sensitivity C
      reactive protein (hs-CRP) in predicting cardiovascular events 2 years after
      stenting in patients with unstable angina (UA) who had not received statin
      pretreatment. METHODS: There were 1,896 patients included in this study. The
      primary end-point was the occurrence of cardiac death or myocardial infarction
      (MI). Secondary endpoints included all-cause death, stent thrombosis (ST), target
      lesion revascularization (TLR), target vessel revascularization (TVR), or a
      composite of major adverse cardiac events (MACE) at 2 years after the procedure.
      RESULTS: During the median follow-up of 2.77 years, 96 patients experienced
      cardiac death (n = 37, 1.95%) or MIs (n = 70, 3.69%), 94 TLRs, 123 TVRs, 215
      MACEs, and 21 definite or probable STs. In multivariable Cox proportional-hazards
      models and discrimination analysis, elevated IL-6 levels were superior to hs-CRP
      in predicting the occurrence not only of cardiac death or MI (HR 1.337, 95% CI
      1.234-1.449, P < 0.001), but also of MACE and late-occurring definite/probable
      ST. Incorporation of IL-6 into conventional variables resulted in significantly
      increased c statistic for the prediction of end-points, with the exception of TLR
      and TVR. CONCLUSION: Elevated IL-6 levels were independent predictors of cardiac
      death or MI, MACE, and late ST in patients with UA who had not received statin
      pretreatment, suggesting a role for IL-6 in the inflammatory risk assessment.
      Pathological studies have confirmed that atherosclerosis is a chronic
      inflammatory disease. Serum levels of high-sensitivity C-reactive protein (hs
      CRP), matrix metalloproteinase, plasminogen activator inhibitor-1, the complement
      components C3a or C5a, and interleukin(IL)-6 were reported to provide strong and
      independent indications of the risk for future cardiovascular (CV) events, even
      among individuals who are thought to be free of vascular disease.

PMID- 24588087
TI  - Therapeutic potential and mechanisms of action of mesenchymal stromal cells for
      Acute Respiratory Distress Syndrome.
AB  - Mesenchymal stem/stromal cells (MSCs) have become the focus of intense research
      effort over the past 10 years, in an effort to harness their regenerative and
      immune-modulating capacity for a variety of clinical conditions. In Acute
      Respiratory Distress Syndrome (ARDS), pre-clinical studies point towards a
      therapy that modulates multiple aspects of a complex disease process. Almost
      universally, these cells have demonstrated an immune modulating phenotype,
      balancing protective host responses with a reduction in damaging inflammation,
      while enhancing bacterial killing. MSCs also lead to more efficient tissue
      repair, and MSC-mediated lung tissue repair and regeneration after ARDS are some
      of the exciting clinical prospects. Recent investigation into the role of
      endogenous MSCs has led to new insights into MSC physiology and its role in
      regulating the immune system. However, significant deficits remain in our
      knowledge regarding the mechanisms of action of MSCs, their efficacy in relevant
      pre-clinical models, and their safety in critically ill patients. These gaps need
      to be addressed before the enormous therapeutic potential of stem cells for
      ALI/ARDS can be realized. 

PMID- 24588088
TI  - Nanofiber scaffolds support bone regeneration associated with pulp stem cells.
AB  - Currently, there are a number of alternatives for bone grafting, though when used
      correctly they present physical, chemical or biological limitations, which
      justifies the pursuit for new alternatives for bone regeneration. This study
      gives a report on the potential for bone regeneration in the use of biodegradable
      nanofibers from poly (lactic-co-glycolic acid) (PLGA) in association with human
      mesenchymal stem cells from dental pulp of deciduous teeth (SCDT). Five samples
      of SCDT were seeded with scaffolds (test) or without scaffolds (control) for cell
      adhesion and viability assay. To evaluate the ability of the association in
      promoting bone formation, critical defects were made in the calvarium of rats
      (n=20), which were then divided into the following groups: I--sham group; II-
      implant of scaffolds; III--scaffolds/ SCDT; and IV--scaffolds/SCDT. They were
      kept for 13 days in osteogenic media. After 60 days, the histomorphometric
      analysis was performed. It was observed that the adherence and viability of SCDT
      in the control and test group were similar throughout the experiment (p>0.05).
      The association of scaffolds/SCDT maintained in osteogenic media, showed greater
      bone formation than the other groups (p<0.05). The study demonstrated that the
      association of SCDT seeded in biodegradable PLGA scaffolds has the ability to
      promote bone regeneration in rats, which is a promising alternative for
      application in regenerative medicine.

PMID- 24588089
TI  - If he can do it, so can they: exposure to counterstereotypically successful
      exemplars prompts automatic inferences.
AB  - After incidental exposure to Blacks who succeeded in counterstereotypical domains
      (e.g., Brown University President Ruth Simmons, Nobel Laureate Toni Morrison),
      participants drew an automatic inference that race was not a success-inhibiting
      factor in modern society. Of note, participants' automatic inferences were not
      simply guided by their explicit reasoning (i.e., their beliefs about what these
      exemplars signify about the state of race relations). Studies 1-3 demonstrated
      the basic automatic inference effect and provided evidence that such effects
      unfolded automatically, without intention or awareness. Study 4 replicated the
      effect in non-race-related domains. Subsequent studies examined what features of
      exemplars (Studies 5 and 6) and inference makers (Studies 7 and 8) prompt
      automatic inferences. Study 5 suggested that counterstereotypically successful
      exemplars prompt racism-denying inferences because they signal what is possible,
      even if not typical. Study 6 demonstrated that when these exemplars succeed in a
      stereotypical domain (e.g., Blacks in athletics), similar automatic inferences
      are not drawn. Those most likely to draw automatic inferences are people
      predisposed to approach the world with inferential thinking: participants
      dispositionally high in need for cognition (Study 7) or experimentally primed to
      think inferentially (Study 8).

PMID- 24588090
TI  - Is a meta-analysis a foundation, or just another brick? Comment on Meltzer,
      McNulty, Jackson, and Karney (2014).
AB  - In a longitudinal data set of married couples, Meltzer, McNulty, Jackson, and
      Karney (2014) reported that partner physical attractiveness is more strongly
      associated with relationship satisfaction for men than for women. Although a
      recent meta-analysis (Eastwick, Luchies, Finkel, & Hunt, in press) provided no
      support for this sex difference across 97 samples and ~30,000 participants,
      Meltzer et al. (2014) responded by outlining 7 criteria required for an
      appropriate test of the sex difference; these criteria eliminate all but 1 study
      from the meta-analysis. In this commentary, we raise 3 concerns about Meltzer et
      al.'s contribution. First, there is weak theoretical and empirical support for
      the criteria they used to dismiss the relevance of the meta-analysis studies.
      Second, if one adds Meltzer et al.'s data to the meta-analysis, all the sex
      differences remain extremely small and nonsignificant, even if one focuses only
      on studies that best conform to Meltzer et al.'s criteria (i.e., married samples,
      objective attractiveness measures). Third, a new data set meeting all 7 criteria
      fails to replicate the Meltzer et al. sex difference; in contrast, data revealed
      that physical attractiveness is, if anything, more strongly associated with the
      trajectory of relationship satisfaction for women than for men. As noted by
      Eastwick, Luchies, et al. (in press), in paradigms where participants evaluate
      partners they have (at a minimum) met face-to-face, the sex difference in the
      association of physical attractiveness with romantic evaluations is (a) extremely
      small on average and (b) unlinked to all cross-study characteristics identified
      to date.

PMID- 24588091
TI  - Men still value physical attractiveness in a long-term mate more than women:
      rejoinder to Eastwick, Neff, Finkel, Luchies, and Hunt (2014).
AB  - Sexual selection theory and parental investment theory suggest that partner
      physical attractiveness should more strongly affect men's relationship outcomes
      than women's relationship outcomes. Nevertheless, the contextual nature of this
      prediction makes serious methodological demands on studies designed to evaluate
      it. Given these theories suggest that men value observable aspects of partner
      attractiveness more than women do only in the context of long-term and
      reproductively viable relationships, they require that studies testing this sex
      difference involve (a) participants in long-term relationships, (b) women of
      child-bearing age, and (c) measures of physical attractiveness that assess
      observable aspects of appearance. In our original article (Meltzer, McNulty,
      Jackson, & Karney, 2014), we applied 7 methodological standards that allowed us
      to meet these 3 criteria and demonstrated that partner physical attractiveness is
      more strongly associated with men's long-term relationship satisfaction than
      women's long-term relationship satisfaction. Eastwick, Neff, Finkel, Luchies, and
      Hunt (2014), in contrast, described an unfocused meta-analysis, a refocused meta
      analysis, and new data that all failed to meet these criteria and, not
      surprisingly, failed to demonstrate such a sex difference. We continue to believe
      that men value physical attractiveness more than women do, that such preferences
      have implications for their evaluations of long-term relationships, and that
      studies properly calibrated to detect such differences will do so.

PMID- 24588092
TI  - Boasts are a boost: achievement prime self-reactivity predicts subsequent
      academic performance.
AB  - The present research tests the hypothesis that self-reactivity following an
      achievement prime reflects the strength of achievement goals and is a predictor
      of future goal-relevant performance. In Studies 1-3, undergraduates reported
      their grade-point averages (GPAs) following either an achievement goal prime or a
      control prime. Academic exaggeration (higher self-reported than official GPA) was
      the indicator of self-reactivity to the prime. Study 1 involved a direct
      achievement goal prime, whereas Studies 2 and 3 involved indirect priming
      techniques. In all 3 experiments, greater academic exaggeration following the
      achievement goal prime (but not the control prime) predicted better academic
      performance a semester later (based on official records). Study 4 demonstrated
      that the magnitude of students' GPA goals mediated the association between
      academic exaggeration and subsequent performance (1 year later). The fact that
      self-reactivity to a single achievement goal prime in the lab predicted later
      performance in "real life" suggests that individual differences in reactivity to
      a specific prime can signal much broader motivational orientations related to the
      primed goal.

PMID- 24588095
TI  - Thermosensitive ionic microgels via surfactant-free emulsion copolymerization and
      in situ quaternization cross-linking.
AB  - A type of thermosensitive ionic microgel was successfully prepared via the
      simultaneous quaternized cross-linking reaction during the surfactant-free
      emulsion copolymerization of N-isopropylacrylamide (NIPAm) as the main monomer
      and 1-vinylimidazole or 4-vinylpyridine as the comonomer. 1,4-Dibromobutane and
      1,6-dibromohexane were used as the halogenated compounds to quaternize the
      tertiary amine in the comonomer, leading to the formation of a cross-linking
      network and thermosensitive ionic microgels. The sizes, morphologies, and
      properties of the obtained ionic microgels were systematically investigated by
      using transmission electron microscopy (TEM), dynamic and static light scattering
      (DLS and SLS), electrophoretic light scattering (ELS), thermogravimetric analyses
      (TGA), and UV-visible spectroscopy. The obtained ionic microgels were spherical
      in shape with narrow size distribution. These ionic microgels exhibited
      thermosensitive behavior and a unique feature of poly(ionic liquid) in aqueous
      solutions, of which the counteranions of the microgels could be changed by anion
      exchange reaction with BF4K or lithium trifluoromethyl sulfonate (PFM-Li). After
      the anion exchange reaction, the ionic microgels were stable in aqueous solution
      and could be well dispersed in the solvents with different polarities, depending
      on the type of counteranion. The sizes and thermosensitive behavior of the ionic
      microgels could be well tuned by controlling the quaternization extent, the type
      of comonomer, halogenated compounds, and counteranions. The ionic microgels
      showed superior swelling properties in aqueous solution. Furthermore, these ionic
      microgels also showed capabilities to encapsulate and release the anionic dyes,
      like methyl orange, in aqueous solutions. 

PMID- 24588096
TI  - Surface-mediated protein disaggregation.
AB  - Preventing protein aggregation is of both biological and industrial importance.
      Interprotein interactions between the hydrophobic residues of the protein are
      known to be the major driving force for protein aggregation. In this article, we
      show how surface chemistry and curvature can be tuned to mitigate these
      interprotein interactions. Our results calculated in the framework of the
      Hydrophobic-Polar (HP) lattice model show that interprotein interactions can be
      drastically reduced by increasing the surface hydrophobicity to a critical value
      corresponding to the adsorption transition of the protein. At this value of
      surface hydrophobicity, proteins lose interprotein contacts to gain surface
      contacts, and thus the surface helps to reduce the interprotein interactions.
      Furthermore, we show that the adsorption of the proteins inside hydrophobic pores
      of optimal sizes are most efficient at both reducing interprotein contacts and
      simultaneously retaining most of the native contacts probably as a result of
      confinement-induced stabilization. 

PMID- 24588093
TI  - Translating personality psychology to help personalize preventive medicine for
      young adult patients.
AB  - The rising number of newly insured young adults brought on by health care reform
      will soon increase demands on primary care physicians. Physicians will face more
      young adult patients, which presents an opportunity for more prevention-oriented
      care. In the present study, we evaluated whether brief observer reports of young
      adults' personality traits could predict which individuals would be at greater
      risk for poor health as they entered midlife. Following the cohort of 1,000
      individuals from the Dunedin Multidisciplinary Health and Development Study
      (Moffitt, Caspi, Rutter, & Silva, 2001), we show that very brief measures of
      young adults' personalities predicted their midlife physical health across
      multiple domains (metabolic abnormalities, cardiorespiratory fitness, pulmonary
      function, periodontal disease, and systemic inflammation). Individuals scoring
      low on the traits of Conscientiousness and Openness to Experience went on to
      develop poorer health even after accounting for preexisting differences in
      education, socioeconomic status, smoking, obesity, self-reported health, medical
      conditions, and family medical history. Moreover, personality ratings from peer
      informants who knew participants well, and from a nurse and receptionist who had
      just met participants for the first time, predicted health decline from young
      adulthood to midlife despite striking differences in level of acquaintance.
      Personality effect sizes were on par with other well-established health risk
      factors such as socioeconomic status, smoking, and self-reported health. We
      discuss the potential utility of personality measurement to function as an
      inexpensive and accessible tool for health care professionals to personalize
      preventive medicine. Adding personality information to existing health care
      electronic infrastructures could also advance personality theory by generating
      opportunities to examine how personality processes influence doctor-patient
      communication, health service use, and patient outcomes.

PMID- 24588097
TI  - Temperature-dependent kinetics of charge transfer, hydrogen-atom transfer, and
      hydrogen-atom expulsion in the reaction of CO+ with CH4 and CD4.
AB  - We have determined the rate constants and branching ratios for the reactions of
      CO(+) with CH4 and CD4 in a variable-temperature selected ion flow tube. We find
      that the rate constants are collisional for all temperatures measured (193-700 K
      for CH4 and 193-500 K for CD4). For the CH4 reaction, three product channels are
      identified, which include charge transfer (CH4(+) + CO), H-atom transfer (HCO(+)
      + CH3), and H-atom expulsion (CH3CO(+) + H). H-atom transfer is slightly
      preferred to charge transfer at low temperature, with the charge-transfer product
      increasing in contribution as the temperature is increased (H-atom expulsion is a
      minor product for all temperatures). Analogous products are identified for the
      CD4 reaction. Density functional calculations on the CO(+) + CH4 reaction were
      also conducted, revealing that the relative temperature dependences of the charge
      transfer and H-atom transfer pathways are consistent with an initial charge
      transfer followed by proton transfer. 

PMID- 24588099
TI  - A new approach to an old hypothesis; phototherapy does not affect ductal patency
      via PGE2 and PGI2.
AB  - OBJECTIVE: Numerous investigations have demonstrated that phototherapy (PT)
      directly or indirectly causes ductal patency by photorelaxation effect. In this
      observational study, we aimed to assess the effect of PT on the incidence of
      patent ductus arteriosus (PDA) together with prostaglandins (PGE2) and (PGI2)
      levels in preterm infants. METHODS: Preterm infants whose gestational age<34
      weeks and who required PT in the first 3 d of life were enrolled in this
      prospective study. The clinical signs of PDA, the data of detailed
      echocardiographic study were recorded and plasma PGE2 and PGI2 levels were
      measured before and after PT. The outcome measures were the status of ductus
      arteriosus and alterations of PGE2 and PGI2 levels under the effect of PT.
      RESULTS: A total of 44 preterm infants were enrolled in the study, of these 21
      (47.7%) were in Group 1 (Non-PDA Group) and 23 (52.3%) were in Group 2 (PDA
      Group). After PT, ductal reopening occurred in three infants (14.3%) in Group 1,
      while ductus closed in four infants in Group 2 (17.3%). PT does not seem to
      effect ductal patency for both groups (p=0.250 and p=0.125, respectively). PGE2
      levels were not different before and after PT for both groups (p=0.087, p=0.408,
      respectively). However, PGI2 levels were significantly decreased after PT in both
      groups (p=0.006, and p=0.003, respectively). CONCLUSION: There was no effect of
      PT on ductal patency. We can conclude that PGs were eliminated simultaneously
      with ductal closure and photorelaxation effect did not influence PG levels.

PMID- 24588100
TI  - Substate federalism and fracking policies: does state regulatory authority trump
      local land use autonomy?
AB  - State officials responsible for the regulation of hydraulic fracturing (fracking)
      operations used in the production of oil and gas resources will inevitably
      confront a key policy issue; that is, to what extent can statewide regulations be
      developed without reducing land use autonomy typically exercised by local
      officials? Most state regulators have historically recognized the economic
      importance of industry jobs and favor the adoption of uniform regulatory
      requirements even if these rules preempt local policymaking authority.
      Conversely, many local officials seek to preserve land use autonomy to provide a
      greater measure of protection for public health and environmental quality goals.
      This paper examines how public officials in three states-Colorado, Pennsylvania,
      and Texas-address the question of state control versus local autonomy through
      their efforts to shape fracking policy decisions. While local officials within
      Texas have succeeded in developing fracking ordinances with relatively little
      interference from state regulators, Colorado and Pennsylvania have adopted a
      tougher policy stance favoring the retention of preemptive oil and gas statutes.
      Key factors that account for between state differences in fracking policy
      decisions include the strength of home rule provisions, gubernatorial
      involvement, and the degree of local experience with industrial economic
      activities. 

PMID- 24588101
TI  - Nicotinamide phosphoribosyltransferase inhibitor is a novel therapeutic candidate
      in murine models of inflammatory lung injury.
AB  - We previously identified the intracellular nicotinamide phosphoribosyltransferase
      (iNAMPT, aka pre-B-cell colony enhancing factor) as a candidate gene promoting
      acute respiratory distress syndrome (ARDS) and ventilator-induced lung injury
      (VILI) with circulating nicotinamide phosphoribosyltransferase potently inducing
      NF-kappaB signaling in lung endothelium. iNAMPT also synthesizes intracellular
      nicotinamide adenine dinucleotide (iNAD) in response to extracellular oxidative
      stress, contributing to the inhibition of apoptosis via ill-defined mechanisms.
      We now further define the role of iNAMPT activity in the pathogenesis of
      ARDS/VILI using the selective iNAMPT inhibitor FK-866. C57/B6 mice were exposed
      to VILI (40 ml/kg, 4 h) or LPS (1.5 mg/kg, 18 h) after osmotic pump delivery of
      FK-866 (100 mg/kg/d, intraperitoneally). Assessment of total bronchoalveolar
      lavage (BAL) protein, polymorphonuclear neutrophil (PMN) levels, cytokine levels
      (TNF-alpha, IL-6, IL-1alpha), lung iNAD levels, and injury scores revealed that
      FK-866-mediated iNAMPT inhibition successfully reduced lung tissue iNAD levels,
      BAL injury indices, inflammatory cell infiltration, and lung injury scores in LPS
      and VILI-exposed mice. FK-866 further increased lung PMN apoptosis, as reflected
      by caspase-3 activation in BAL PMNs. These findings support iNAMPT inhibition via
      FK-866 as a novel therapeutic agent for ARDS via enhanced apoptosis in
      inflammatory PMNs. 

PMID- 24588103
TI  - Filter-free image sensor pixels comprising silicon nanowires with selective color
      absorption.
AB  - The organic dye filters of conventional color image sensors achieve the
      red/green/blue response needed for color imaging, but have disadvantages related
      to durability, low absorption coefficient, and fabrication complexity. Here, we
      report a new paradigm for color imaging based on all-silicon nanowire devices and
      no filters. We fabricate pixels consisting of vertical silicon nanowires with
      integrated photodetectors, demonstrate that their spectral sensitivities are
      governed by nanowire radius, and perform color imaging. Our approach is
      conceptually different from filter-based methods, as absorbed light is converted
      to photocurrent, ultimately presenting the opportunity for very high photon
      efficiency. 

PMID- 24588102
TI  - In search of novel drug target sites on estrogen receptors using RNA aptamers.
AB  - Estrogen receptor alpha (ERalpha) is a well-validated drug target for a majority
      of breast cancers. But the target sites on this receptor are far from
      exhaustively defined. Almost all ER antagonists in clinical use function by
      binding to the ligand-binding pocket to occlude agonist access. Resistance to
      this type of drugs may develop over time, not caused by the change of ERalpha
      itself, but by changes in ER associated proteins. This observation is fueling the
      development of reagents that downregulate ER activity through novel binding
      sites. However, it is challenging to find general ER antagonists that act
      independently from other known ER ligands. In this report, we describe the
      utility of RNA aptamers in the search for new drug target sites on ERalpha. We
      have identified three high affinity aptamers and characterized one of them in
      detail. This aptamer interacted with ERalpha in a way not affected by the
      presence or absence of either the steroidal ligands or the estrogen response DNA
      elements, and effectively inhibited ER-mediated transcriptional activation in a
      breast cancer cell line. Serving as a novel drug lead, it may also be used to
      guide the rational chemical synthesis of small molecule drugs or to perform
      screens of small molecule libraries for those that are able to displace the
      aptamer from its binding site. 

PMID- 24588104
TI  - Chronic ocular hypertensive rat model using microbead injection: comparison of
      polyurethane, polymethylmethacrylate, silica and polystyene microbeads.
AB  - PURPOSE: To establish and assess an ocular hypertensive rat model using
      intracameral injection with various microbeads of different sizes and materials.
      METHODS: Chronic elevation of intraocular pressure (IOP) was induced by the
      injection of various microbeads into the anterior chamber of Sprague-Dawley rat
      eyes. We compared the IOPs induced by the injection of different microbeads [7-
      and 17-um polyurethane (PU), 7- and 15-um polymethylmethacrylate (PMMA), 13-um
      silica, and 15-um polystyrene (PS)] and selected the appropriate microbeads for a
      chronic ocular hypertensive model in terms of IOP elevation and adverse events.
      IOP changes were observed for 4 weeks after microbead injections. Axonal
      degeneration was assessed with transmission electron microscopic photographs and
      RGC loss was assessed with retrograde labeling. RESULTS: Seventy-eight rats were
      included. Three days after a single injection of microbeads, IOPs were increased
      by 24.0% by 7-um PU microbeads, 101.8% by 17-um PU microbeads, 56.6% by 7-um PMMA
      microbeads, 22.0% by 15-um PMMA microbeads, 153.0% by 13-um silica microbeads,
      and 34.7% by 15-um PS microbeads. 17-um PU microbeads produced constant IOP
      elevation with good reproducibility (standard deviation of <6.5 mmHg). Silica
      injected eyes showed severe inflammation. Sustained IOP elevation by two
      injections of 17-um PU microbeads resulted in a 42% axon loss and 36.5% RGC loss
      (p < 0.05, Mann-Whitney U test). CONCLUSIONS: PU microbead injections offer an
      applicable and versatile model for a chronic ocular hypertensive model in rats.
      Among several biomaterials, PU microbeads produced a more stable IOP elevation
      without adverse events.

PMID- 24588105
TI  - Synthesis and evaluation of new Hsp90 inhibitors based on a 1,4,5-trisubstituted
      1,2,3-triazole scaffold.
AB  - Ruthenium catalyzed 1,3-cycloaddition (click chemistry) of an azido moiety
      installed on dihydroxycumene scaffold with differently substituted aryl
      propiolates gave a new family of 1,4,5-trisubstituted triazole carboxylic acid
      derivatives that showed high affinity toward Hsp90 associated with cell
      proliferation inhibition, both in nanomolar range. The 1,5 arrangement of the
      resorcinol, the aryl moieties, and the presence of an alkyl (secondary) amide in
      position 4 of the triazole ring were essential to get high activity. Docking
      simulations suggested that the triazoles penetrate the Hsp90 ATP binding site.
      Some 1,4,5-trisubstituted triazole carboxamides induced dramatic depletion of the
      examined client proteins and a very strong increase in the expression levels of
      the chaperone Hsp70. In vitro metabolic stability and in vivo preliminary studies
      on selected compounds have shown promising results comparable to the potent Hsp90
      inhibitor NVP-AUY922. One of them, (compound 18, SST0287CL1) was selected for
      further investigation as the most promising drug candidate. 

PMID- 24588106
TI  - Preliminary findings for a brief posttraumatic stress intervention in primary
      mental health care.
AB  - A team of clinicians at a small rural Veterans' Health Administration (VHA)
      medical center piloted a brief psychological intervention for posttraumatic
      stress in a primary mental health care setting. Symptom measures were completed
      by veterans before and after receiving the brief trauma treatment (BTT), and were
      then analyzed using paired t tests. In our uncontrolled study, we found a
      statistically insignificant improvement in symptoms of posttraumatic stress
      disorder, though there were statistically significant, but not clinically
      significant, improvements in depression and general anxiety. The intervention may
      enhance subsequent specialty mental health engagement. Fifty-one veterans
      (62.20%) went on to receive psychotherapy in a specialty mental health setting,
      which represents a substantial increase in specialty psychotherapy engagement
      compared to reports elsewhere in the literature. Lack of controlled comparison
      precludes definitive conclusions, but the current preliminary results support
      future studies of brief psychological interventions in primary care settings,
      including randomized controlled comparisons.

PMID- 24588107
TI  - Communication between VA providers and sexual and gender minority veterans: a
      pilot study.
AB  - Approximately one million gay and lesbian Americans are veterans, and rates of
      engagement in the Veterans Affairs (VA) health care system may be increasing for
      both sexual and gender minority veterans. Very little research has examined the
      experience of these veterans when receiving care at VA health care facilities.
      The purpose of this study was to explore the experiences, beliefs, and
      preferences of lesbian, gay, bisexual, or transgender (LGBT) veterans in their
      communication with VA health care providers. LGBT veterans (n = 58) participated
      in focus groups or individual interviews and completed self-report measures at
      two southern VA hospitals. Approximately 2/3 of veterans report that none of
      their VA providers have specifically asked about their sexual orientation, and
      24% of the veterans indicate that they have not disclosed their orientation to
      any VA provider. Although some veterans want providers to initiate these
      discussions, veterans also expressed fears about disclosure and its possible
      negative consequences. Similarly, LGBT veterans report varied opinions about the
      appropriateness of routine assessment of minority status. Only 28% of these
      veterans experience VA as welcoming to them as LGBT veterans. Systematic training
      is needed for all VA providers about the rationale for assessing sexual and
      gender orientation. Staff education should include specific skills for initiating
      these assessments, and ways of responding to veteran concerns about discussing
      this topic in the VA health care system.

PMID- 24588108
TI  - Bronsted acid catalyzed cascade reactions of 2-[(2
      aminophenyl)ethynyl]phenylamine derivatives with aldehydes: a new approach to the
      synthesis of 2,2'-disubstituted 1H,1'H-3,3'-biindoles.
AB  - An unusual Bronsted acid catalyzed cascade reaction of 2-[(2
      aminophenyl)ethynyl]phenylamine derivatives with aryl(heteroaryl)aldehydes to
      afford an efficient alternative entry into 2,2'-disubstituted-1H,1'H-3,3'
      biindoles under metal-free conditions is reported. 

PMID- 24588109
TI  - Electron transfer in pnicogen bonds.
AB  - As a new type of noncovalent interactions, pnicogen bond between a VA group
      element (N, P, and As) and an electron donor (Lewis base) has grabbed attention
      in recent several years. Here we employ the block-localized wave function (BLW)
      based energy decomposition scheme to probe the bonding nature in a series of
      substituted phosphines X(n)PH(3-n) complexed with ammonia. As the BLW method can
      derive the optimal monomer orbitals in a complex with the electron transfer among
      monomers quenched, we can effectively examine the HOMO-LUMO interaction in these
      pnicogen bonding systems. Among various energy components, electron transfer
      energy together with the polarization energy dominates the pnicogen bonding
      energy. Although usually it is assumed that the electron transfer from ammonia to
      substituted phosphines occurs in the form of n -> sigma*(XP) hyperconjugative
      interaction, we identify a kind of new pathway when X = NO2 and CN, i.e., n ->
      dpi*, which results from the interaction between the pi orbital of cyano or nitro
      substituent and d orbitals on P. But still this picture of electron transfer
      using a single pair of orbitals is greatly simplified, as the electron density
      difference (EDD) maps corresponding to the overall electron transfer processes
      show the accumulation of electron density on the P side opposite to the X-P bond,
      with insignificant or even negligible gain of electron density on the substituent
      group side. Thus, the EDD maps tend to support the concept of sigma-hole in
      pnicogen bonds.

PMID- 24588110
TI  - Update on B-cell targeted therapies for systemic lupus erythematosus.
AB  - INTRODUCTION: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease
      characterized by flares and remission, leading to accrual of organ damage over
      time as a result of persistent tissue inflammation and treatment-related
      complications. Novel therapies aiming at better treatment response and fewer
      adverse effects are being tested in the pipeline. AREAS COVERED: This review
      summarizes the B-cell abnormalities observed in patients with SLE, and updates
      recent data on the efficacy and safety of B-cell targeted therapies in the
      treatment of SLE. The pitfalls of clinical trial design and future directions of
      the development of SLE therapeutics are discussed. EXPERT OPINION: The
      variability of clinical response to treatment in SLE reflects the clinical and
      immunological heterogeneity of the disease. The treatment plan for patients with
      SLE should be individualized with the aim of eradicating disease activity,
      preventing flares and minimizing treatment-related complications. Despite the
      disappointment of recent clinical trials, B-cell remains the promising target of
      future SLE therapies. Results from ongoing clinical trials on B-cell targeted
      biological agents are eagerly awaited.

PMID- 24588111
TI  - Antibody against immunoglobulin E contained in blood components as causative
      factor for anaphylactic transfusion reactions.
AB  - BACKGROUND: Determining the mechanism underlying the development of transfusion
      reactions is important in transfusion therapy. Two bags of fresh-frozen plasma
      obtained from a donor (index donor) were implicated in two cases of anaphylactic
      transfusion reactions. STUDY DESIGN AND METHODS: The serum prepared from the
      index donor plasma transfused into the second patient (Patient 2) was evaluated
      using cord blood-derived mast cells (CBMCs) incubated with Patient 2 plasma. The
      component in the serum required for the degranulation was determined and
      quantified by chromatography in combination with degranulation assay, Western
      blot analysis, and enzyme-linked immunosorbent assay. The component in the plasma
      required for CBMC sensitization was determined using human immunoglobulin (Ig)E
      or normal plasma in place of Patient 2 plasma in the assay. Sera collected from
      the index donor between 2001 and 2008 were examined for the CBMC degranulation
      factor. RESULTS: The donor serum activated CBMCs incubated with Patient 2 plasma.
      The IgG fraction of the donor serum induced degranulation of CBMCs sensitized
      with IgE or plasma containing a normal IgE concentration. The IgG anti-IgE at a
      concentration higher than 2200 ng/mL, which showed CBMC degranulation activity,
      was detected in the donor sera for at least 7 years. CONCLUSION: Transfusion of a
      high concentration of the anti-IgE in the donor plasma was suggested to induce
      mast cell degranulation in the patients leading to the development of
      anaphylactic transfusion reactions. Antibodies existing in not only the patient
      circulation but also the transfused blood might cause transfusion-induced
      anaphylaxis.

PMID- 24588112
TI  - Pitfalls in comparing modern hair and fossil bone collagen C and N isotopic data
      to reconstruct ancient diets: a case study with cave bears (Ursus spelaeus).
AB  - Stable isotope analyses provide one of the few means to evaluate diet of extinct
      taxa. However, interpreting isotope data from bone collagen of extinct animals
      based on isotopic patterns in different tissues of modern animal proxies is
      precarious. For example, three corrections are needed before making comparisons
      of recent hair and ancient bone collagen: calibration of carbon-13 variations in
      atmospheric CO2, different isotopic discrimination between diet-hair keratin and
      diet-bone collagen, and time averaging of bone collagen versus short-term record
      in hair keratin. Recently, Robu et al. [Isotopic evidence for dietary flexibility
      among European Late Pleistocene cave bears (Ursus spelaeus). Can J Zool.
      2013;91:227-234] published an article comparing extant carbon (delta(13)C) and
      nitrogen (delta(15)N) stable isotopic data of European cave bear bone collagen
      with those of Yellowstone Park grizzly bear hair in order to test the prevailing
      assumption of a largely vegetarian diet among cave bears. The authors concluded
      that cave bears were carnivores. This work is unfortunately unfounded as the
      authors failed to consider the necessary corrections listed above. When these
      corrections are applied to the Romanian cave bears, these individuals can be then
      interpreted without involving consumption of high trophic-level food, and
      environmental changes are probably the reason for the unusual isotopic
      composition of these cave bears in comparison with other European cave bears,
      rather than a change of diet. We caution researchers to pay careful attention to
      these factors when interpreting feeding ecology of extinct fauna using stable
      isotope techniques.

PMID- 24588114
TI  - Expectant management of a herniated amniotic sac presenting as silent uterine
      rupture: a case report and literature review.
AB  - Foetal membranes bulging into the abdominal cavity is a unique initial
      manifestation of silent or complete uterine rupture during pregnancy. Since
      silent uterine rupture has potential risk for complete uterine rupture, which
      leads to acute life-threatening complications for both the mother and baby, it is
      difficult to determine whether to manage expectantly or surgically, including
      repair of the uterine wall or termination of the pregnancy, especially in the
      early second trimester. We present here a case of a herniated amniotic sac with
      overstretched uterine wall of the fundus presenting as silent uterine rupture,
      which was incidentally detected on routine ultrasonography at 18 weeks' gestation
      in a 38-year-old primigravida with a history of myomectomy for diffuse uterine
      leiomyomatosis. Magnetic resonance imaging examination revealed that the
      myometrium thickness was fully maintained at the site of the foetal membranes
      ballooning. The pregnancy was therefore managed expectantly and continued to
      successful delivery at 30 weeks' gestation. The precise assessment of the uterine
      wall may be essential to manage a herniated amniotic sac presenting as silent
      uterine rupture and to optimise the outcome of the pregnancy. We review all cases
      of a herniated amniotic sac out of focally overstretched uterine wall before 34
      weeks' gestation.

PMID- 24588115
TI  - Melanoma prognosis in Europe: far from equal.
AB  - BACKGROUND: Comprehensive, population-based analysis of melanoma survival
      throughout Europe is hindered by the uneven coverage and quality of European
      cancer registries, and by logistical and financial shortcomings. Mortality-to
      incidence ratios (MIRs) have been used as a proxy for estimating survival for
      multiple cancers and to model melanoma prognosis, higher MIR values reflecting
      poorer prognosis. Updated and improved pan-European estimates of mortality and
      incidence rates for melanoma have become available through the International
      Agency for Research of Cancer project Globocan 2008, showing marked differences
      among European countries. OBJECTIVES: To analyse MIRs for melanoma across Europe
      and their relationship with national health expenditures, aiming to identify
      countries and regions with disproportionately poor prognosis. METHODS: Estimated
      age-standardized rates of melanoma incidence and mortality provided by Globocan
      2008 were used to calculate the MIR for each European country and region. Total
      health expenditures per capita in European countries for 2008 were provided by
      the World Health Organization/Global Health Observatory. The potential
      correlation between MIR and total health expenditure per capita was analysed
      through Pearson's correlation. RESULTS: Mortality-to-incidence ratios for
      melanoma ranged between 0.09 in Switzerland and 0.44 in Latvia. The regional
      average MIR was the highest in Central and Eastern Europe at 0.35; the lowest was
      in Western Europe, at 0.13. We found a strong inverse correlation between the
      individual nation's total health expenditure per capita and the calculated
      melanoma MIR (r = -0.76, P < 0.05). CONCLUSIONS: While further improvement of
      melanoma registration is necessary, our findings reveal sharp disparities in the
      prognosis of melanoma across the Continent, correlated with significant
      differences in health care expenditures.

PMID- 24588116
TI  - Thermo-sensitive polymer-grafted carbon nanotubes with temperature-controlled
      phase transfer behavior between water and a hydrophobic ionic liquid.
AB  - Thermo-sensitive polymer-grafted carbon nanotubes were prepared by surface
      initiated atom transfer radical polymerization and carefully characterized. A
      reversible, temperature-induced phase transfer behavior of these organic
      inorganic hybrids between water (with a decrease in temperature to 20  degrees C)
      and a hydrophobic ionic liquid, 1-ethyl-3-methylimidazolium
      bis(trifluoromethylsulfonyl)imide ([Emim]NTf2) (with an increase in temperature
      to 90  degrees C), was observed. Mechanism analysis suggests that this reversible
      phase transfer between water and [Emim]NTf2 is due to the relative affinity of
      the two solvents for the poly(ethylene oxide) units grafted on the carbon
      nanotubes. Our results pave the way for further design of carbon nanotube-based,
      recyclable phase transfer vehicles as well as heterogeneous catalysts suited for
      a water-hydrophobic ionic liquid biphasic system. 

PMID- 24588117
TI  - C-reactive protein levels in hereditary angioedema.
AB  - Hereditary angioedema (HAE) patients experience recurrent episodes of angioedema
      attacks that can be painful, disfiguring and even life-threatening. The disorder
      results from a mutation in the gene that controls the synthesis of C1-inhibitor
      (C1INH). C1INH is a major regulator of activation of the contact system. It is
      often assumed that attacks results from uncontrolled local activation of the
      contact system with subsequent formation of bradykinin. To evaluate the
      involvement of inflammatory reactions in HAE, we analysed C-reactive protein
      (CRP) levels. HAE patients included in a clinical database of recombinant human
      C1-inhibitor (rhC1INH) studies were evaluated. For the current study we analysed
      CRP levels when patients were asymptomatic, during a clinical attack and in a
      follow-up period, and correlated these with the clinical manifestations of the
      attack. Data from 68 HAE patients were analysed and included CRP levels on 273
      occasions. While asymptomatic, 20% of the patients analysed had increased CRP. At
      the onset of the attack (P = 0.049) and during the next 24 h CRP rose
      significantly (P = 0.002) in patients with an abdominal location, and post-attack
      levels were significantly higher in these patients than in patients with attacks
      at other locations (P = 0.034). In conclusion, CRP levels are elevated in a
      substantial proportion of asymptomatic HAE patients. Levels of CRP increase
      significantly during an abdominal attack. These data suggest low-grade systemic
      inflammatory reactions in HAE patients as well as a triggering event for attacks
      that starts prior to symptom onset. 

PMID- 24588118
TI  - Inhibition of interleukin-1beta-induced matrix metalloproteinase expression in
      human corneal fibroblasts by tranilast.
AB  - PURPOSE: Matrix metalloproteinases (MMPs) mediate the degradation of
      extracellular matrix proteins and are implicated in the pathogenesis of corneal
      ulceration. Tranilast, a clinically approved antiallergy drug, has been found to
      exert various anti-inflammatory effects. We examined the effects of this agent on
      MMP expression in cultured corneal fibroblasts. METHODS: Human corneal
      fibroblasts were cultured in the absence or presence of interleukin-1beta (IL
      1beta) or tranilast. The release of MMPs into culture supernatants was assessed
      by immunoblot analysis and gelatin zymography, and the cellular abundance of MMP
      mRNAs was determined by reverse transcription and real-time polymerase chain
      reaction analysis. The phosphorylation of mitogen-activated protein kinases
      (MAPKs) and the nuclear factor-kappaB (NF-kappaB) inhibitor IkappaB-alpha was
      examined by immunoblot analysis. RESULTS: The IL-1beta-induced expression of MMP
      1, -2, and -3 in corneal fibroblasts was inhibited by tranilast in a
      concentration- and time-dependent manner. It was also attenuated by synthetic
      inhibitors of MAPK or NF-kappaB signaling pathways. Tranilast inhibited the IL
      1beta-induced phosphorylation of the MAPKs extracellular signal-regulated kinase
      (ERK), p38, and c-Jun NH(2)-terminal kinase (JNK) as well as the phosphorylation
      and degradation of IkappaB-alpha. Tranilast did not exhibit cytotoxicity for
      corneal fibroblasts. CONCLUSIONS: Tranilast inhibits the IL-1beta-induced
      production of MMP-1, -2, and -3 by human corneal fibroblasts, with this action
      likely being mediated through suppression of MAPK and NF-kappaB signaling
      pathways. Tranilast thus warrants further investigation as a potential treatment
      for corneal ulceration on the basis of its inhibition of MMP expression in
      corneal fibroblasts.

PMID- 24588119
TI  - Renal sympathetic denervation in patients with aortic dissection.
AB  - BACKGROUND: We report on feasibility, safety, and mid-term outcomes of renal
      sympathetic denervation (RSD) in hypertensive patients after endovascular
      treatment for aortic dissection. METHODS: Six patients were subjected to RSD
      after receiving endovascular treatment for complicated aortic dissection. Between
      April 2011 and May 2012, RSD procedure was applied for persistent hypertension
      despite maximized antihypertensive drug therapy using the Symplicity(r) catheter
      system. Endovascular aortic treatment was performed for malperfusion or rapid
      expansion by virtue of a stent-graft system (Valiant(r), n = 5) or an open cell
      stent (Smart(r); n = 1). RESULTS: Systolic blood pressure (BP) was 189.8 +/- 32.2
      mmHg and diastolic BP 96.2 +/- 11.1 mmHg at baseline on 24 hours readings; after
      RSD, a successful reduction to 129.5 +/- 11.8 mmHg (P = 0.004) for systolic and
      to 77.7 +/- 10.7 (P = 0.004) for diastolic BP at 3-month follow-up was documented
      on ambulatory 24-hour BP readings with sustained reduction at 1-year follow-up
      (127.2 +/- 11.8 mmHg [P = 0.002] and 77.7 +/- 7.7 [P = 0.011]). CONCLUSION: RSD
      using the Symplicity(r) catheter system is feasible and safe in hypertensive
      patients previously subjected to endovascular repair for complicated aortic
      dissection.

PMID- 24588120
TI  - Synthesis and biological evaluation of sulfonilamidothienopyrimidinone
      derivatives as novel anti-inflammatory agents.
AB  - Eight new sulfonilamidothienopyrimidinone derivatives (1-8) were synthesized and
      evaluated for their antiinflammatory activity on the human keratinocyte line NCTC
      2544. The potential anti-inflammatory activity of the derivatives (1-8) was
      evaluated by determining, through Western blot, the expression of cyclooxygenase
      (COX)-2, inducible NO synthase (iNOS), intercellular adhesion molecule-1 (ICAM
      1), and the release of prostaglandins (PG)E2 and interleukin- 8 (IL-8). Moreover,
      through ELISA assay, the release of monocyte chemoattractant protein-1 (MCP-1),
      and interleukin- 8 (IL-8) was analyzed. Our results demonstrated that the
      derivatives 3, 5, 6 and 8 act as excellent inhibitors of inflammatory markers:
      iNOS, COX-2, ICAM-1, MCP-1, and IL-8. These findings could be useful for the
      development of new drugs for the treatment of various inflammatory pathologies. 

PMID- 24588121
TI  - Hapten-grafted graphene as a transducer for homogeneous competitive immunoassay
      of small molecules.
AB  - A hapten-grafted graphene-based biosensor by integrating both the graphene
      nanosheets and immunoassay sensing technologies was developed for ultrasensitive
      homogeneous competitive immunoassay of small molecules. The structure of hapten
      grafted graphene avoids the activity loss of biomolecules immobilized onto the
      graphene surface and is beneficial to preserve the binding affinity between small
      molecule and its specific antibody. The sandwich structure formed between hapten
      grafted graphene nanosheets and fluorescence-labeled antibody increases the
      quenching efficiency of the organic dye, thereby resulting in high signal-to
      background ratios and improved sensitivity for Bisphenol A (BPA) detection. On
      the basis of fluorescence resonance energy transfer (FRET) and homogeneous
      competitive immunoassay mechanism, high BPA concentrations in the sample reduce
      the amount of fluorescence-labeled anti-BPA antibody bound to graphene-BPA
      nanosheets, thus resulting in remarkable fluorescence signals. The linear
      quantification of BPA over concentration ranges from 0.5 to 50 nM with a
      detection limit determined as 0.12 nM. These findings show that the proposed
      method provides a powerful tool for the rapid and sensitive detection of small
      molecules in biological and environmental samples. 

PMID- 24588123
TI  - Adalimumab in the treatment of rheumatoid arthritis.
AB  - Introduction: Rheumatoid arthritis (RA) is a systemic inflammatory disease that
      causes increased morbidity and mortality. The treatment of the disease has
      considerably advanced with the addition of biological agents targeting pro
      inflammatory cytokines such as tumor necrosis factor (TNF). Adalimumab (ADA) is
      one of the currently available five TNF inhibitors for clinical use in RA. It is
      a fully humanized monoclonal antibody which may be prescribed as monotherapy or
      in combination with methotrexate or other disease-modifying antirheumatic drugs.
      Areas covered: This review summarizes the recent available data on efficacy and
      safety of ADA in patients with early and established RA as well as improvement of
      quality of life and finally we provide data on biologic drug comparison. Expert
      opinion: ADA has been evaluated in various randomized placebo-controlled trials
      in RA, prospective observational studies as well as open-label extensions of the
      original double-blind trials providing experience and data about the long-term
      efficacy and safety of the drug. Effectiveness of the drug is sustained, while in
      most cases RA patients treated with ADA experienced a slower radiographic
      progression and consequently less disability and improved health-related quality
      of life outcomes. Clinical trials demonstrated no new safety signals and a safety
      profile consistent with that of the anti-TNF class.

PMID- 24588122
TI  - Dietary cholesterol protects against alcohol-induced cerebral artery
      constriction.
AB  - BACKGROUND: Binge drinking represents the major form of excessive alcohol
      (ethanol [EtOH]) consumption in the United States. Episodic (such as binge)
      drinking results in blood alcohol levels (BAL) of 18 to 80 mM and leads to
      alcohol-induced cerebral artery constriction (AICAC). AICAC was shown to arise
      from EtOH-induced inhibition of large-conductance, calcium/voltage-gated
      potassium (BK) channels in the vascular smooth muscle. Factors that modulate BK
      channel-mediated AICAC remain largely unknown. METHODS: Male Sprague Dawley rats
      were placed on high-cholesterol (2% of cholesterol) diet for 18 to 23 weeks.
      Their littermates were placed on control iso-caloric diet. AICAC was evaluated
      both in vivo and in vitro, by means of pial arteriole diameter monitoring through
      a closed cranial window and diameter measurements of isolated, pressurized
      cerebral arteries. Cholesterol level in the cerebral artery tissue was
      manipulated by methyl-beta-cyclodextrin to reverse dietary-induced accumulation
      of cholesterol. BK channel surface presence on the plasma membrane of cerebral
      artery myocytes was evaluated by immunofluorescence staining. BK channel function
      in pressurized cerebral artery was assessed using selective BK channel blocker
      paxilline. RESULTS: Within 5 minutes of 50 mM EtOH injection into carotid artery
      in vivo, arteriole diameter decreased by 20% in control group. Pial arteriole
      constriction was significantly reduced in rats on high-cholesterol diet,
      resulting in only 10% reduction in diameter. BAL in both groups, however,
      remained the same. Significant reduction in AICAC in group on high-cholesterol
      diet compared to control was also observed after middle cerebral artery
      dissection and in vitro pressurization at 60 mmHg, this reduction remaining after
      endothelium removal. Cholesterol level in de-endothelialized cerebral arteries
      was significantly increased in rats on high-cholesterol diet. Removal of
      excessive cholesterol content restored AICAC to the level observed in cerebral
      arteries of rats on normal diet. Immunofluorescence staining of BK channel
      forming and accessory, smooth muscle-specific beta1 subunit in freshly isolated
      cerebral artery myocyte showed that high-cholesterol diet did not down-regulate
      surface presence of BK protein. However, paxilline-induced cerebral artery
      constriction was diminished in arteries from rats on high-cholesterol diet.
      CONCLUSIONS: Our data indicate that dietary cholesterol protects against AICAC.
      This protection is caused by cholesterol buildup in the arterial tissue and
      diminished function (but not surface presence) of EtOH target-BK channel.

PMID- 24588124
TI  - Amine-tethered adsorbents based on three-dimensional macroporous silica for CO(2)
      capture from simulated flue gas and air.
AB  - New covalently tethered CO2 adsorbents are synthesized through the in situ
      polymerization of N-carboxyanhydride (NCA) of l-alanine from amine-functionalized
      three-dimensional (3D) interconnected macroporous silica (MPS). The
      interconnected macropores provide low-resistant pathways for the diffusion of CO2
      molecules, while the abundant mesopores ensure the high pore volume. The
      adsorbents exhibit high molecular weight (of up to 13058 Da), high amine loading
      (more than 10.98 mmol N g(-1)), fast CO2 capture kinetics (t1/2 < 1 min), high
      adsorption capacity (of up to 3.86 mmol CO2 g(-1) in simulated flue gas and 2.65
      mmol CO2 g(-1) in simulated ambient air under 1 atm of dry CO2), as well as good
      stability over 120 adsorption-desorption cycles, which allows the overall CO2
      capture process to be promising and sustainable. 

PMID- 24588125
TI  - Real-time visualization of nanocrystal solid-solid transformation pathways.
AB  - Measurement and understanding of the microscopic pathways materials follow as
      they transform is crucial for the design and synthesis of new metastable phases
      of matter. Here we employ femtosecond single-shot X-ray diffraction techniques to
      measure the pathways underlying solid-solid phase transitions in cadmium sulfide
      nanorods, a model system for a general class of martensitic transformations.
      Using picosecond rise-time laser-generated shocks to trigger the transformation,
      we directly observe the transition state dynamics associated with the wurtzite-to
      rocksalt structural phase transformation in cadmium sulfide with atomic-scale
      resolution. A stress-dependent transition path is observed. At high peak
      stresses, the majority of the sample is converted directly into the rocksalt
      phase with no evidence of an intermediate prior to rocksalt formation. At lower
      peak stresses, a transient five-coordinated intermediate structure is observed
      consistent with previous first principles modeling. 

PMID- 24588126
TI  - Copper-catalyzed carboxamide-directed ortho amination of anilines with
      alkylamines at room temperature.
AB  - In this report, a highly efficient method for the room temperature installation
      of alkyl amino motifs onto the ortho position of anilines via Cu-catalyzed
      carboxamide-directed amination with alkylamines is described. This method offers
      a practical solution for the rapid synthesis of complex arylamines from simple
      starting materials and enables new planning strategies for the construction of
      arylamine-containing pharmacophores. A single electron transfer (SET)-mediated
      mechanism is proposed. 

PMID- 24588127
TI  - A human rights approach: the work of public health nurses.

PMID- 24588128
TI  - Administrators' perspectives on changing practice in end-of-life care in a state
      prison system.
AB  - OBJECTIVE: Sentencing trends have created a demographic shift in prison
      populations. Greater numbers of inmates are aging and dying in prison, creating a
      demand for enhanced end-of-life (EOL) care. Changing practice to meet escalating
      care demands in correction settings is complicated by economic constraints,
      attitudinal barriers, and organizational features. This study explored
      perspectives of EOL care held by administrators in a state prison system to
      reveal challenges to changing practice to meet the needs of inmates suffering
      advanced illness and dying in prison. DESIGN AND SAMPLE: Qualitative interviews
      were conducted with 12 administrators from the central office of a state
      department of corrections. MEASURES: Semi-structured discussion guide. RESULTS:
      Key influences impacting EOL care services included: local prison culture,
      treatment versus security focus, case-by-case consideration, public sentiment,
      budget neutral approaches, and conflicting views of service targets. CONCLUSIONS:
      These findings revealed the organizational structures, attitudes, and beliefs
      held by the administrative echelon of a state prison system and were used to
      guide the derivation of discrete approaches to changing practice in this complex
      system. Contextual evaluation permitted a much deeper understanding of the
      influences on changing practice in this hierarchical bureaucracy. This type of
      preliminary evaluation is crucial to infusing new practice initiatives in complex
      organizations caring for stigmatized, at-risk populations.

PMID- 24588129
TI  - Recidivism after release from a prison nursery program.
AB  - OBJECTIVE: To analyze 3-year recidivism after release from a prison nursery, a
      secure unit that allows imprisoned women to care for their infants. DESIGN AND
      SAMPLE: Descriptive study of 139 women who co-resided with their infants between
      2001 and 2007 in a New York State prison nursery. MEASURES: Administrative
      criminal justice data were analyzed along with prospective study data on
      demographic, mental health, and prison nursery policy-related factors. RESULTS:
      Results reflect a sample of young women of color with histories of clinically
      significant depressive symptoms and substance dependence, who were convicted of
      nonviolent crimes and had multiple prior arrests. Three years after release 86.3%
      remained in the community. Only 4% of women returned to prison for new crimes.
      Survival modeling indicated that women who had previously violated parole had a
      significantly shorter mean return to prison time than those who were in the
      nursery for a new crime. CONCLUSION: Women released from a prison nursery have a
      low likelihood of recidivism. Innovative interventions are needed to address
      incarceration's public health effects. Nurses can partner with criminal justice
      organizations to develop, implement, and evaluate programs to ensure the health
      needs of criminal justice involved people and their families are met.

PMID- 24588131
TI  - Making basic health care accessible to rural communities: a case study of Kiang
      West district in rural Gambia.
AB  - This study focuses on lack of access to basic health care, which is one of the
      hindrances to the development of the poor, and subjects them to the poverty
      penalty. It also focuses on contributing to the Bottom of the Pyramid in a
      general sense, in addition to meeting the health needs of communities where
      people live on less than $1 a day. Strengthened multistakeholder responses and
      better-targeted, low-cost prevention, and care strategies within health systems
      are suggested to address the health burdens of poverty-stricken communities. In
      this study, a multistakeholder model which includes the government, World Health
      Organization, United Nations Children Emergency Fund, and the Medical Research
      Council was created to highlight the collaborative approach in rural Gambia. The
      result shows infant immunization and antenatal care coverage were greatly
      improved which contributes to the reduction in mortality. This case study also
      finds that strategies addressing health problems in rural communities are
      required to achieve 'Millennium Development Goals'. In particular, actual
      community visits to satellite villages within a district (area of study) are
      extremely vital to making health care accessible. 

PMID- 24588098
TI  - Copper active sites in biology.

PMID- 24588132
TI  - Adaptation of a best practice guideline to strengthen client-centered care in
      public health.
AB  - Best practice guidelines (BPGs) were developed by the Registered Nurses
      Association of Ontario (RNAO) to support evidence-based nursing practice. One
      Ontario public health unit chose to implement the BPG on client-centered care
      (CCC). A critical review of this BPG revealed issues that would hinder successful
      implementation within a public health setting. These included a focus on the
      client as an individual, the predominance of acute care exemplars and training
      resources that were not representative of public health nursing practice, and the
      need to reconcile the enforcement roles of public health with the BPG principles.
      The purpose of this article is to describe the process of adapting the CCC BPG to
      more accurately reflect the broad scope of public health nursing practice. A
      model for CCC in public health nursing context is presented and processes for
      implementing, evaluating, and sustaining CCC are described. 

PMID- 24588130
TI  - A syndemic model of women incarcerated in community jails.
AB  - OBJECTIVE: The purpose of this study was to test whether variations in substance
      abuse, mental health diagnoses, individual experiences of violence, community
      experiences of violence, and incarceration history may be reduced to a single
      underlying syndemic factor for a sample of women incarcerated in three Midwestern
      U.S. jails. DESIGN AND SAMPLE: Secondary data analysis of a cross-sectional study
      of a medical utilization survey; initial confirmatory factor analysis tested fit
      of model; modification indexes provided confirmatory fit. 290 women incarcerated
      in three urban Midwestern U.S. jails. MEASURES: Demographics and variables
      associated with women's criminal justice experience and sexual health risk were
      assessed. The analysis included women's mental health, drug dependence, childhood
      sexual and physical abuse, and partner violence. RESULTS: The final model had
      four variables with significant pathways: childhood sexual abuse, childhood
      physical abuse, domestic violence, and mental health diagnoses. The fit of this
      model was very good (chi(2) (1) = 0.6; CFI = 1.00; standardized RMR = 0.0147),
      strongly suggesting the intertwined nature of the variables. CONCLUSION:
      Clarification of the specific components in a syndemic model for this population
      will allow for the implementation of interventions with the appropriate inclusion
      of content. In interventions and clinical practice, public health nurses should
      consider these interrelationships.

PMID- 24588133
TI  - Immersive simulation education: a novel approach to pandemic preparedness and
      response.
AB  - Pandemic management involves strategic and tactical concepts rarely experienced
      with other disasters. To comprehend the enormity of these tasks and experience
      the critical decision-making required, local public health and other stakeholders
      participate in tabletop and functional exercises. Students in Master of Public
      Health (MPH) programs not only rarely experience this educational format, but
      also are seldom afforded substantive time to appreciate the critical decision
      making that is unique to pandemics. An immersive semester-long simulation
      exercise was created to educate graduate public health students about pandemics.
      Students in a MPH course were divided into groups representing county health
      departments. During the semester, students collaborated and completed incident
      command training, received audio lectures, and materials concerning an imminent
      pandemic. The students then participated in the 2.5-hr facilitated tabletop
      exercises in the classroom. A survey was developed to assess their perceptions of
      the experience. Most students felt more knowledgeable afterward and thought that
      this training style was innovative, entertaining, educational, and recommended it
      to fellow students and colleagues. The students believed that delivering a
      tabletop exercise in this fashion was educational and entertaining. It gave the
      students a better appreciation of the role of public health in managing the
      complexities associated with pandemics. 

PMID- 24588134
TI  - Measurements of the foramen magnum and mandible in relation to sex using CBCT.
AB  - The purpose of this study was to evaluate pre-existing CBCT images of a large
      sample of adult females and males to provide data on foramen magnum and
      mandibular measures of sexual dimorphism for use as a reference sample in cases
      of establishing identity in unknown fragmentary skulls. The study group consisted
      of 161 adult patients. 3D images of the patients were assessed retrospectively.
      FM measurements were obtained from reformatted axial sections. Six mandibular
      measurements were taken. According to the results, the study identified four
      mandibular measurements as final predictors of sex which are as follows: the
      gonial angle (G-angle) and ramus length (Ramus-L), gonion-gnathion length (G-G-L)
      and bigonial breadth (BG-Br). It was found that the cross-validated grouped
      overall predictive accuracy was 83.2% for FM and mandible measurements. It could
      correctly identify males in 77.3% and females in 87.4% of the cases. To assess
      sexual dimorphism, the gonial angle and ramus, gonion-gnathion lengths, and
      bigonial breadth of the mandible and sagittal diameter of the FM may be used on
      CBCT images.

PMID- 24588135
TI  - Cephalochromin induces G0/G1 cell cycle arrest and apoptosis in A549 human non
      small-cell lung cancer cells by inflicting mitochondrial disruption.
AB  - The fungus-derived compound cephalochromin, isolated from the fermented broth of
      Cosmospora vilior YMJ89051501, shows growth-inhibitory and apoptotic activity
      against human lung cancer A549 cells in a concentration-dependent manner with an
      IC50 value of 2.8 MUM at 48 h. Cephalochromin induced cell cycle arrest at the
      G0/G1 phase through down-regulation of cyclin D1, cyclin E, Cdk 2, and Cdk 4
      expressions. Cephalochromin markedly increased the hypodiploid sub-G1 phase
      (apoptosis) of the cell cycle at 48 h as measured by flow cytometric analysis.
      Reactive oxygen species generation and loss of the mitochondrial membrane
      potential (MMP) were also markedly induced by cephalochromin. Moreover, the
      immunoblotting assays showed that cephalochromin reduced survivin and Bcl-xL
      expression and induced the activation of caspase-8, -9, and -3 and the cleavage
      of poly(ADP-ribose) polymerase, indicating the involvement of a caspase signaling
      cascade. The caspase inhibitor Z-VAD-fmk significantly suppressed cephalochromin
      induced apoptosis. Cephalochromin also triggered LC3 II, autophagic marker,
      expression. Taken together, this is the first report that cephalochromin induced
      an antiproliferative effect on human lung cancer cells through mitochondrial
      disruption and down-regulation of survivin, leading to cell cycle arrest at the
      G0/G1 phase, loss of MMP, and subsequently apoptotic cell death. 

PMID- 24588136
TI  - Cytotoxic and genotoxic activity of some Helleborus species.
AB  - Despite their known toxic properties, various Helleborus species are used as
      medicaments in folk medicine to treat some diseases and health conditions. As the
      main mechanism of many cytostatic drugs is based on their cytotoxic activity,
      there is potential for the toxicity of hellebore to be used in anticancer
      therapy. This study tested the geno- and cytotoxic effects of extracts of three
      hellebore taxa (Helleborus odorus, Helleborus multifidus and Helleborus
      hercegovinus) on meristemic onion (Alliumcepa L.) cells and human lymphocytes.
      Treatments with Helleborus extracts induced cytotoxic and cytostatic effects in
      meristemic onion cells as well as in cultivated cytokinesis-blocked human
      lymphocytes. Cytokinesis-block micronucleus cytome assay indicated that
      treatments with hellebore extracts induce genotoxic effects in human lymphocytes,
      and that the significant mechanism of their antiproliferative activity is
      apoptosis induction. 

PMID- 24588138
TI  - Forms of Safety and Their Impact on Health: An Exploration of HIV/AIDS-Related
      Risk and Resilience Among Trans Women in Lebanon.
AB  - Using minority stress theory, the authors investigated risk behaviors of
      transgender women (trans women) in Lebanon. Using semistructured interviews, the
      authors explored six areas: relationships with family and friends; openness about
      gender and sexuality; experiences with stigma; sexual behavior; attitudes and
      behaviors regarding HIV testing; and perceived HIV-related norms among
      transgender peers. Participants voiced the importance of different forms of
      safety: social/emotional, physical, sexual, and financial. Strategies for
      obtaining safety were negotiated differently depending on social, behavioral, and
      structural factors in the environment. In this article, we provide study findings
      from the perspectives of trans women, their exposure to stigma, and the necessary
      navigation of environments characterized by transphobia.

PMID- 24588139
TI  - Involvement of mGlu5 receptor in 3-nitropropionic acid-induced oxidative stress
      in rat striatum.
AB  - OBJECTIVES: The excitotoxin 3-nitropropionic acid (3-NP) induces a suitable
      experimental model of Huntington's disease (HD). This compound induces
      neurodegeneration via glutamatergic activation and oxidative stress, suggesting
      that the metabotropic glutamate receptor blockage and free radical scavenging are
      potential therapeutic targets in HD. In this study, we evaluated the role of 3
      [(2-methyl-1,3-thiazol-4-yl) ethynyl]-pyridine (MTEP), a selective mGlu5 receptor
      antagonist, in a 3-NP model of HD. METHODS: We administered 3-NP (20 mg/kg,
      intraperitoneal) to rats for 4 days. MTEP at doses of 2.5 and 5 mg/kg was
      administered 30 min before 3-NP. Behavioral tests and biochemical experiments
      were performed to assess the effects of 3-NP and the ability of MTEP to
      ameliorate these changes. RESULTS: 3-NP administration induced body weight loss,
      decreased locomotor activity, and inhibition of succinate dehydrogenase and Na(+)
      K(+) adenosine triphosphate (ATP)ase activities in rat striatum. We also observed
      increases in reactive species (RS) levels and glutathione reductase activity,
      decreased non-protein thiol levels, and an inhibition of glutathione peroxidase
      activity in the striatum of rats treated with 3-NP. Notably, all of these effects
      were attenuated by MTEP treatment. DISCUSSION: Our results demonstrate the
      neuroprotective effect of MTEP and reinforce the involvement of mGluR5 in 3-NP
      induced oxidative stress in rat striatum.

PMID- 24588140
TI  - Communication: from rods to helices: evidence of a screw-like nematic phase.
AB  - Evidence of a special chiral nematic phase is provided using numerical simulation
      and Onsager theory for systems of hard helical particles. This phase appears at
      the high density end of the nematic phase, when helices are well aligned, and is
      characterized by the C2 symmetry axes of the helices spiraling around the nematic
      director with periodicity equal to the particle pitch. This coupling between
      translational and rotational degrees of freedom allows a more efficient packing
      and hence an increase of translational entropy. Suitable order parameters and
      correlation functions are introduced to identify this screw-like phase, whose
      main features are then studied as a function of radius and pitch of the helical
      particles. Our study highlights the physical mechanism underlying a similar
      ordering observed in colloidal helical flagella [E. Barry, Z. Hensel, Z. Dogic,
      M. Shribak, and R. Oldenbourg, Phys. Rev. Lett. 96, 018305 (2006)] and raises the
      question of whether it could be observed in other helical particle systems, such
      as DNA, at sufficiently high densities. 

PMID- 24588141
TI  - Communication: multireference equation of motion coupled cluster: a transform and
      diagonalize approach to electronic structure.
AB  - The novel multireference equation-of-motion coupled-cluster (MREOM-CC) approaches
      provide versatile and accurate access to a large number of electronic states. The
      methods proceed by a sequence of many-body similarity transformations and a
      subsequent diagonalization of the transformed Hamiltonian over a compact
      subspace. The transformed Hamiltonian is a connected entity and preserves spin-
      and spatial symmetry properties of the original Hamiltonian, but is no longer
      Hermitean. The final diagonalization spaces are defined in terms of a complete
      active space (CAS) and limited excitations (1h, 1p, 2h, ...) out of the CAS. The
      methods are invariant to rotations of orbitals within their respective subspaces
      (inactive, active, external). Applications to first row transition metal atoms
      (Cr, Mn, and Fe) are presented yielding results for up to 524 electronic states
      (for Cr) with an rms error compared to experiment of about 0.05 eV. The accuracy
      of the MREOM family of methods is closely related to its favorable extensivity
      properties as illustrated by calculations on the O2-O2 dimer. The computational
      costs of the transformation steps in MREOM are comparable to those of closed
      shell Coupled Cluster Singles and Doubles (CCSD) approach. 

PMID- 24588142
TI  - Rationalization of the Hubbard U parameter in CeO(x) from first principles:
      unveiling the role of local structure in screening.
AB  - The density functional theory (DFT)+U method has been widely employed in
      theoretical studies on various ceria systems to correct the delocalization bias
      in local and semi-local DFT functionals with moderate computational cost. We
      present a systematic and quantitative study, aiming to gain better understanding
      of the dependence of Hubbard U on the local atomic arrangement. To rationalize
      the Hubbard U of Ce 4f, we employed the first principles linear response method
      to compute Hubbard U for Ce in ceria clusters, bulks, and surfaces. We found that
      the Hubbard U varies in a wide range from 4.3 eV to 6.7 eV, and exhibits a strong
      correlation with the Ce coordination number and Ce-O bond lengths, rather than
      the Ce 4f valence state. The variation of the Hubbard U can be explained by the
      changes in the strength of local screening due to O -> Ce intersite transitions. 

PMID- 24588143
TI  - A stochastic model for kinesin bidirectional stepping.
AB  - In this paper, a hand-over-hand stochastic model for the dynamics of the
      conventional kinesin is constructed. In the model, both forward and backward
      motions are taken into consideration. First passage time distributions, average
      velocities, dwell times, and forward/backward step ratios are investigated based
      on the model. A good agreement between the results of the model and experimental
      data is achieved under a variety of external loads. 

PMID- 24588144
TI  - A bridge-functional-based classical mapping method for predicting the correlation
      functions of uniform electron gases at finite temperature.
AB  - Efficient and accurate prediction of the correlation functions of uniform
      electron gases is of great importance for both practical and theoretical
      applications. This paper presents a bridge-functional-based classical mapping
      method for calculating the correlation functions of uniform spin-unpolarized
      electron gases at finite temperature. The bridge functional is formulated by
      following Rosenfeld's universality ansatz in combination with the modified
      fundamental measure theory. The theoretical predictions are in good agreement
      with recent quantum Monte Carlo results but with negligible computational cost,
      and the accuracy is better than a previous attempt based on the hypernetted-chain
      approximation. We find that the classical mapping method is most accurate if the
      effective mass of electrons increases as the density falls. 

PMID- 24588145
TI  - Analysis of geometric phase effects in the quantum-classical Liouville formalism.
AB  - We analyze two approaches to the quantum-classical Liouville (QCL) formalism that
      differ in the order of two operations: Wigner transformation and projection onto
      adiabatic electronic states. The analysis is carried out on a two-dimensional
      linear vibronic model where geometric phase (GP) effects arising from a conical
      intersection profoundly affect nuclear dynamics. We find that the Wigner-then
      Adiabatic (WA) QCL approach captures GP effects, whereas the Adiabatic-then
      Wigner (AW) QCL approach does not. Moreover, the Wigner transform in AW-QCL leads
      to an ill-defined Fourier transform of double-valued functions. The double-valued
      character of these functions stems from the nontrivial GP of adiabatic electronic
      states in the presence of a conical intersection. In contrast, WA-QCL avoids this
      issue by starting with the Wigner transform of single-valued quantities of the
      full problem. As a consequence, GP effects in WA-QCL can be associated with a
      dynamical term in the corresponding equation of motion. Since the WA-QCL approach
      uses solely the adiabatic potentials and non-adiabatic derivative couplings as an
      input, our results indicate that WA-QCL can capture GP effects in two-state
      crossing problems using first-principles electronic structure calculations
      without prior diabatization or introduction of explicit phase factors. 

PMID- 24588147
TI  - Implicit solvation model for density-functional study of nanocrystal surfaces and
      reaction pathways.
AB  - Solid-liquid interfaces are at the heart of many modern-day technologies and
      provide a challenge to many materials simulation methods. A realistic first
      principles computational study of such systems entails the inclusion of solvent
      effects. In this work, we implement an implicit solvation model that has a firm
      theoretical foundation into the widely used density-functional code Vienna ab
      initio Software Package. The implicit solvation model follows the framework of
      joint density functional theory. We describe the framework, our algorithm and
      implementation, and benchmarks for small molecular systems. We apply the
      solvation model to study the surface energies of different facets of
      semiconducting and metallic nanocrystals and the SN2 reaction pathway. We find
      that solvation reduces the surface energies of the nanocrystals, especially for
      the semiconducting ones and increases the energy barrier of the SN2 reaction. 

PMID- 24588146
TI  - Calculation of absorption spectra involving multiple excited states: approximate
      methods based on the mixed quantum classical Liouville equation.
AB  - We investigate the calculation of absorption spectra based on the mixed quantum
      classical Liouville equation (MQCL) methods. It has been shown previously that,
      for a single excited state, the averaged classical dynamics approach to calculate
      the linear and nonlinear spectroscopy can be derived using the MQCL formalism.
      This work focuses on problems involving multiple coupled excited state surfaces,
      such as in molecular aggregates and in the cases of coupled electronic states. A
      new equation of motion to calculate the dipole-dipole correlation functions
      within the MQCL formalism is first presented. Two approximate methods are then
      proposed to solve the resulted equations of motion. The first approximation
      results in a mean field approach, where the nuclear dynamics is governed by
      averaged forces depending on the instantaneous electronic states. A modification
      to the mean field approach based on first order moment expansion is also
      proposed. Numerical examples including calculation of the absorption spectra of
      Frenkel exciton models of molecular aggregates, and the pyrazine molecule are
      presented. 

PMID- 24588148
TI  - Double-hybrid density-functional theory with meta-generalized-gradient
      approximations.
AB  - We extend the previously proposed one-parameter double-hybrid density-functional
      theory [K. Sharkas, J. Toulouse, and A. Savin, J. Chem. Phys. 134, 064113 (2011)]
      to meta-generalized-gradient-approximation (meta-GGA) exchange-correlation
      density functionals. We construct several variants of one-parameter double-hybrid
      approximations using the Tao-Perdew-Staroverov-Scuseria (TPSS) meta-GGA
      functional and test them on test sets of atomization energies and reaction
      barrier heights. The most accurate variant uses the uniform coordinate scaling of
      the density and of the kinetic energy density in the correlation functional, and
      improves over both standard Kohn-Sham TPSS and second-order Moller-Plesset
      calculations. 

PMID- 24588137
TI  - Fluorescent sensors for measuring metal ions in living systems.

PMID- 24588149
TI  - The relativistic polarization propagator for the calculation of electronic
      excitations in heavy systems.
AB  - In this work, we present a new four-component implementation of the polarization
      propagator for accurate calculations of excited states in heavy systems.
      Differences to existing nonrelativistic realizations are detailed and the
      energetically lowest final states of the ns(2)np(6) -> ns(2)np(5)(n + 1)s(1) and
      ns(2)np(6) -> ns(2)np(5)(n + 1)p(1) transitions in noble gases are calculated and
      compared with experimental data. Already for the light atoms Ne and Ar spin-orbit
      coupling leads to noticeable zero field splitting that gradually increases in the
      heavier homologues and eventually invalidates the LS-based description of singlet
      and triplet excited states. For all four noble gases Ne through Xe, we observe a
      very good agreement with experimental transition energies in the considered
      energetic range where the extended version of the propagator implementation in
      general yields better excitation energy differences than the strict variant. In
      the extended version, off-diagonal first-order contributions in the two-particle
      two-hole block are included that are not present in the strict variant. In case
      of Kr and Xe, nonrelativistic approaches already exhibit unacceptable deviations
      in the reproduction of transition energies and the spectral structure. The
      obtained excited final states are analyzed in terms of atomic contributions to
      the donor and acceptor orbitals constituting the corresponding wave functions.
      The relativistic polarization propagator provides a consistent description of
      electron correlation and relativistic effects especially relevant for the heavier
      systems where these two contributions are no longer separable. 

PMID- 24588150
TI  - Recovering position-dependent diffusion from biased molecular dynamics
      simulations.
AB  - All atom molecular dynamics (MD) models provide valuable insight into the
      dynamics of biophysical systems, but are limited in size or length by the high
      computational demands. The latter can be reduced by simulating long term
      diffusive dynamics (also known as Langevin dynamics or Brownian motion) of the
      most interesting and important user-defined parts of the studied system, termed
      collective variables (colvars). A few hundred nanosecond-long biased MD
      trajectory can therefore be extended to millisecond lengths in the colvars
      subspace at a very small additional computational cost. In this work, we develop
      a method for determining multidimensional anisotropic position- and timescale
      dependent diffusion coefficients (D) by analysing the changes of colvars in an
      existing MD trajectory. As a test case, we obtained D for dihedral angles of the
      alanine dipeptide. An open source Mathematica((r)) package, capable of
      determining and visualizing D in one or two dimensions, is available at
      https://github.com/lbf-ijs/DiffusiveDynamics. Given known free energy and D, the
      package can also generate diffusive trajectories. 

PMID- 24588151
TI  - Monte Carlo simulations for the free energies of C60 and C70 fullerene crystals
      by acceptance ratio method and expanded ensemble method.
AB  - Accurate values of the free energies of C60 and C70 fullerene crystals are
      obtained using expanded ensemble method and acceptance ratio method combined with
      the Einstein-molecule approach. Both simulation methods, when tested for Lennard
      Jones crystals, give accurate results of the free energy differing from each
      other in the fifth significant digit. The solid-solid phase transition
      temperature of C60 crystal is determined from free energy profiles, and found to
      be 260 K, which is in good agreement with experiment. For C70 crystal, using the
      potential model of Sprik et al. [Phys. Rev. Lett. 69, 1660 (1992)], low
      temperature solid-solid phase transition temperature is found to be 160 K
      determined from the free energy profiles. Whereas this is somewhat lower than the
      experimental value, it is in agreement with conventional molecular simulations,
      which validates the methodological consistency of the present simulation method.
      From the calculations of the free energies of C60 and C70 crystals, we note the
      significance of symmetry number for crystal phase needed to properly account for
      the indistinguishability of orientationally disordered states. 

PMID- 24588152
TI  - Nucleation near the eutectic point in a Potts-lattice gas model.
AB  - We use the Potts-lattice gas model to study nucleation at and near the eutectic
      composition. We use rare-event methods to compute the free energy landscape for
      the competing nucleation products, and short trajectories at the barrier top to
      obtain prefactors. We introduce a procedure to tune the frequency of semigrand
      Monte Carlo moves so that the dynamics of a small closed system roughly resemble
      those of an infinite system. The non-dimensionalized nucleation rates follow
      trends as predicted by the classical nucleation theory. Finally, we develop
      corrections that convert free energy surfaces from closed (canonical) simulations
      into free energy surfaces from open (semigrand) simulations. The new corrections
      extend earlier corrections to now address situations like nucleation at the
      eutectic point where two products nucleate competitively. 

PMID- 24588153
TI  - The virial theorem for the Polarizable Continuum Model.
AB  - The electronic virial theorem is extended to molecular systems within the
      framework of the Polarizable Continuum Model (PCM) to describe solvation effects.
      The theorem is given in the form of a relation involving the components of the
      energy (kinetic and potential) of a molecular solute and its electrostatic
      properties (potential and field) at the boundary of the cavity in the continuum
      medium. The virial theorem is also derived in the presence of the Pauli repulsion
      component of the solute-solvent interaction. Furthermore, it is shown that these
      forms of the PCM virial theorem may be related to the virial theorem of more
      simple systems as a molecule in the presence of fixed point charges, and as an
      atom in a spherical box with confining potential. 

PMID- 24588154
TI  - Vibrational quasi-degenerate perturbation theory with optimized coordinates:
      applications to ethylene and trans-1,3-butadiene.
AB  - A perturbative extension to optimized coordinate vibrational self-consistent
      field (oc-VSCF) is proposed based on the quasi-degenerate perturbation theory
      (QDPT). A scheme to construct the degenerate space (P space) is developed, which
      incorporates degenerate configurations and alleviates the divergence of
      perturbative expansion due to localized coordinates in oc-VSCF (e.g., local O-H
      stretching modes of water). An efficient configuration selection scheme is also
      implemented, which screens out the Hamiltonian matrix element between the P space
      configuration (p) and the complementary Q space configuration (q) based on a
      difference in their quantum numbers (lambdapq = ?s|ps - qs|). It is demonstrated
      that the second-order vibrational QDPT based on optimized coordinates (oc-VQDPT2)
      smoothly converges with respect to the order of the mode coupling, and
      outperforms the conventional one based on normal coordinates. Furthermore, an
      improved, fast algorithm is developed for optimizing the coordinates. First, the
      minimization of the VSCF energy is conducted in a restricted parameter space, in
      which only a portion of pairs of coordinates is selectively transformed. A
      rational index is devised for this purpose, which identifies the important
      coordinate pairs to mix from others that may remain unchanged based on the
      magnitude of harmonic coupling induced by the transformation. Second, a cubic
      force field (CFF) is employed in place of a quartic force field, which bypasses
      intensive procedures that arise due to the presence of the fourth-order force
      constants. It is found that oc-VSCF based on CFF together with the pair selection
      scheme yields the coordinates similar in character to the conventional ones such
      that the final vibrational energy is affected very little while gaining an order
      of magnitude acceleration. The proposed method is applied to ethylene and trans
      1,3-butadiene. An accurate, multi-resolution potential, which combines the MP2
      and coupled-cluster with singles, doubles, and perturbative triples level of
      electronic structure theory, is generated and employed in the oc-VQDPT2
      calculation to obtain the fundamental tones as well as selected
      overtones/combination tones coupled to the fundamentals through the Fermi
      resonance. The calculated frequencies of ethylene and trans-1,3-butadiene are
      found to be in excellent agreement with the experimental values with a mean
      absolute error of 8 and 9 cm(-1), respectively. 

PMID- 24588155
TI  - Monte Carlo configuration interaction with perturbation corrections for
      dissociation energies of first row diatomic molecules: C2, N2, O2, CO, and NO.
AB  - Dissociation energies for the diatomic molecules C2, N2, O2, CO, and NO are
      estimated using the Monte Carlo configuration interaction (MCCI) and augmented by
      a second order perturbation theory correction. The calculations are performed
      using the correlation consistent polarized valence "triple zeta" atomic orbital
      basis and resulting dissociation energies are compared to coupled cluster
      calculations including up to triple excitations (CCSDT) and Full Configuration
      Interaction Quantum Monte Carlo (FCIQMC) estimates. It is found that the MCCI
      method readily describes the correct behavior for dissociation for the diatomics
      even when capturing only a relatively small fraction (~80%) of the correlation
      energy. At this level only a small number of configurations, typically O(10(3))
      from a FCI space of dimension O(10(14)), are required to describe dissociation.
      Including the perturbation correction to the MCCI estimates, the difference in
      dissociation energies with respect to CCSDT ranges between 1.2 and 3.1 kcal/mol,
      and the difference when comparing to FCIQMC estimates narrows to between 0.5 and
      1.9 kcal/mol. Discussions on MCCI's ability to recover static and dynamic
      correlations and on the form of correlations in the electronic configuration
      space are presented. 

PMID- 24588156
TI  - Gradient of molecular Hartree-Fock-Bogoliubov energy with a linear combination of
      atomic orbital quasiparticle wave functions.
AB  - The analytical gradient for the atomic-orbital-based Hartree-Fock-Bogoliubov
      (HFB) energy functional, the modified form of which was proposed by Staroverov
      and Scuseria to account for the static electron correlation [J. Chem. Phys. 117,
      11107 (2002)], is derived. Interestingly, the Pulay force for the HFB energy is
      expressed with the same formula as that for the Hartree-Fock method. The
      efficiency of the present HFB energy gradient is demonstrated in the geometry
      optimizations of conjugated and biradical systems. The geometries optimized by
      using the HFB method with the appropriate factor zeta, which controls the degree
      of static correlation included, are found to show good agreement with those
      obtained by using a complete active-space self-consistent field method, although
      they are significantly dependent on zeta. 

PMID- 24588157
TI  - Multiple time step integrators in ab initio molecular dynamics.
AB  - Multiple time-scale algorithms exploit the natural separation of time-scales in
      chemical systems to greatly accelerate the efficiency of molecular dynamics
      simulations. Although the utility of these methods in systems where the
      interactions are described by empirical potentials is now well established, their
      application to ab initio molecular dynamics calculations has been limited by
      difficulties associated with splitting the ab initio potential into fast and
      slowly varying components. Here we present two schemes that enable efficient time
      scale separation in ab initio calculations: one based on fragment decomposition
      and the other on range separation of the Coulomb operator in the electronic
      Hamiltonian. We demonstrate for both water clusters and a solvated hydroxide ion
      that multiple time-scale molecular dynamics allows for outer time steps of 2.5
      fs, which are as large as those obtained when such schemes are applied to
      empirical potentials, while still allowing for bonds to be broken and reformed
      throughout the dynamics. This permits computational speedups of up to 4.4x,
      compared to standard Born-Oppenheimer ab initio molecular dynamics with a 0.5 fs
      time step, while maintaining the same energy conservation and accuracy. 

PMID- 24588158
TI  - Hyperspectral imaging with in-line interferometric femtosecond stimulated Raman
      scattering spectroscopy.
AB  - We present the hyperspectral imaging capabilities of in-line interferometric
      femtosecond stimulated Raman scattering. The beneficial features of this method,
      namely, the improved signal-to-background ratio compared to other applicable
      broadband stimulated Raman scattering methods and the simple experimental
      implementation, allow for a rather fast acquisition of three-dimensional raster
      scanned hyperspectral data-sets, which is shown for PMMA beads and a lipid
      droplet in water as a demonstration. A subsequent application of a principle
      component analysis displays the chemical selectivity of the method. 

PMID- 24588159
TI  - How to measure a complete set of polarization-dependent differential cross
      sections in a scattering experiment with aligned reagents?
AB  - Polarization-dependent differential cross section (PDDCS) is one of the three
      vector correlations (k, k('), j) in molecular collisions, which provides the most
      detailed insights into the steric requirements of chemical reactions, i.e., how
      the reactivity depends on the polarization of reagents. Only quite recently has
      such quantity been fully realized experimentally in the study of the reaction of
      the aligned CHD3(v1 = 1, |jK? = |10?) molecules with Cl((2)P3/2) atoms.
      Theoretically, PDDCS is a relatively new concept; experimental realization of the
      theoretical construct requires some careful considerations that are not readily
      available in the literature. Here, we present the "know-how" behind the full
      PDDCS measurements to fill the gaps and to provide a clear roadmap for future
      applications. To make the connection apparent between the methodology presented
      here and the stereodynamics revealed in previous reports, the same Cl + aligned
      CHD3 reaction is used for illustration. 

PMID- 24588160
TI  - Observing and preventing rubidium runaway in a direct-infusion xenon-spin
      hyperpolarizer optimized for high-resolution hyper-CEST (chemical exchange
      saturation transfer using hyperpolarized nuclei) NMR.
AB  - Xenon is well known to undergo host-guest interactions with proteins and
      synthetic molecules. As xenon can also be hyperpolarized by spin exchange optical
      pumping, allowing the investigation of highly dilute systems, it makes an ideal
      nuclear magnetic resonance probe for such host molecules. The utility of xenon as
      a probe can be further improved using Chemical Exchange Saturation Transfer using
      hyperpolarized nuclei (Hyper-CEST), but for highly accurate experiments requires
      a polarizer and xenon infusion system optimized for such measurements. We present
      the design of a hyperpolarizer and xenon infusion system specifically designed to
      meet the requirements of Hyper-CEST measurements. One key element of this design
      is preventing rubidium runaway, a chain reaction induced by laser heating that
      prevents efficient utilization of high photon densities. Using thermocouples
      positioned along the pumping cell we identify the sources of heating and
      conditions for rubidium runaway to occur. We then demonstrate the effectiveness
      of actively cooling the optical cell to prevent rubidium runaway in a compact
      setup. This results in a 2-3-fold higher polarization than without cooling,
      allowing us to achieve a polarization of 25% at continuous flow rates of 9 ml/min
      of (129)Xe. The simplicity of this design also allows it to be retrofitted to
      many existing polarizers. Combined with a direction infusion system that reduces
      shot-to-shot noise down to 0.56% we have captured Hyper-CEST spectra in
      unprecedented detail, allowing us to completely resolve peaks separated by just
      1.62 ppm. Due to its high polarization and excellent stability, our design allows
      the comparison of underlying theories of host-guest systems with experiment at
      low concentrations, something extremely difficult with previous polarizers. 

PMID- 24588161
TI  - Observation of separate cation and anion electrophoretic mobilities in pure ionic
      liquids.
AB  - Ionic liquids (ILs) continue to show relevance in many fields, from battery
      electrolytes, to carbon capture, to advanced separations. These highly ion-dense
      fluids present unique challenges in understanding their electrochemical
      properties due to deviations in behavior from existing electrolyte theories. Here
      we present a novel characterization of ILs using electrophoretic NMR (ENMR) to
      determine separate cation and anion mobilities. This method uses an applied
      electric field coincident with a pulsed magnetic field gradient to encode the E
      field driven flow into NMR signals for cations ((1)H) and anions ((19)F). We
      describe the detailed design of these experiments, including quantitative
      analysis of artifact mitigation and necessary control experiments. We then
      explore mobilities and diffusion coefficients for two representative ILs: 1-ethyl
      3-methyl imidazolium tetrafluoroborate ([C2mim][BF4]) and 1-ethyl-3-methyl
      imidazolium trifluoromethanesulfonate ([C2mim][TfO]). We further use the
      individual ion mobilities to calculate the bulk net conductivity, which closely
      agrees with bulk conductivity measurements obtained using impedance spectroscopy.
      These observations represent the first reliable measurements of cation and anion
      mobilities in pure ILs, with errors of +/-7%. We discuss this advanced
      experimental methodology in detail, as well as implications of these sensitive
      measurements for understanding conduction mechanisms in ion-dense electrolytes. 

PMID- 24588162
TI  - Diffusion-assisted selective dynamical recoupling: a new approach to measure
      background gradients in magnetic resonance.
AB  - Dynamical decoupling, a generalization of the original NMR spin-echo sequence, is
      becoming increasingly relevant as a tool for reducing decoherence in quantum
      systems. Such sequences apply non-equidistant refocusing pulses for optimizing
      the coupling between systems, and environmental fluctuations characterized by a
      given noise spectrum. One such sequence, dubbed Selective Dynamical Recoupling
      (SDR) [P. E. S. Smith, G. Bensky, G. A. Alvarez, G. Kurizki, and L. Frydman,
      Proc. Natl. Acad. Sci. 109, 5958 (2012)], allows one to coherently reintroduce
      diffusion decoherence effects driven by fluctuations arising from restricted
      molecular diffusion [G. A. Alvarez, N. Shemesh, and L. Frydman, Phys. Rev. Lett.
      111, 080404 (2013)]. The fully-refocused, constant-time, and constant-number-of
      pulses nature of SDR also allows one to filter out "intrinsic" T1 and T2
      weightings, as well as pulse errors acting as additional sources of decoherence.
      This article explores such features when the fluctuations are now driven by
      unrestricted molecular diffusion. In particular, we show that diffusion-driven
      SDR can be exploited to investigate the decoherence arising from the frequency
      fluctuations imposed by internal gradients. As a result, SDR presents a unique
      way of probing and characterizing these internal magnetic fields, given an a
      priori known free diffusion coefficient. This has important implications in
      studies of structured systems, including porous media and live tissues, where the
      internal gradients may serve as fingerprints for the system's composition or
      structure. The principles of this method, along with full analytical solutions
      for the unrestricted diffusion-driven modulation of the SDR signal, are
      presented. The potential of this approach is demonstrated with the generation of
      a novel source of MRI contrast, based on the background gradients active in an ex
      vivo mouse brain. Additional features and limitations of this new method are
      discussed. 

PMID- 24588163
TI  - Effect of chemical substitutions on photo-switching properties of 3-hydroxy
      picolinic acid studied by ab initio methods.
AB  - Effect of chemical substitutions to the molecular structure of 3-hydroxy
      picolinic acid on photo-switching properties of the system operating on excited
      state intramolecular double proton transfer (d-ESIPT) process [M. F. Rode and A.
      L. Sobolewski, Chem. Phys. 409, 41 (2012)] was studied with the aid of electronic
      structure theory methods. It was shown that simultaneous application of electron
      donating and electron-withdrawing substitutions at certain positions of the
      molecular frame increases the height of the S0-state tautomerization barrier
      (ensuring thermal stability of isomers) and facilitates a barrierless access to
      the S1/S0 conical intersection from the Franck-Condon region of the S1 potential
      energy surface. Results of study point to the conclusion that the most
      challenging issue for practical design of a fast molecular photoswitch based on d
      ESIPT phenomenon are to ensure a selectivity of optical excitation of a given
      tautomeric form of the system. 

PMID- 24588164
TI  - Spin-symmetry conversion in methyl rotors induced by tunnel resonance at low
      temperature.
AB  - Field-cycling NMR in the solid state at low temperature (4.2 K) has been employed
      to measure the tunneling spectra of methyl (CH3) rotors in phenylacetone and
      toluene. The phenomenon of tunnel resonance reveals anomalies in (1)H
      magnetization from which the following tunnel frequencies have been determined:
      phenylacetone, nut = 6.58 +/- 0.08 MHz; toluene, nut(1) = 6.45 +/- 0.06 GHz and
      nut(2) = 7.07 +/- 0.06 GHz. The tunnel frequencies in the two samples differ by
      three orders of magnitude, meaning different experimental approaches are
      required. In phenylacetone the magnetization anomalies are observed when the
      tunnel frequency matches one or two times the (1)H Larmor frequency. In toluene,
      doping with free radicals enables magnetization anomalies to be observed when the
      tunnel frequency is equal to the electron spin Larmor frequency. Cross
      polarization processes between the tunneling and Zeeman systems are proposed and
      form the basis of a thermodynamic model to simulate the tunnel resonance spectra.
      These invoke space-spin interactions to drive the changes in nuclear spin
      symmetry. The tunnel resonance lineshapes are explained, showing good
      quantitative agreement between experiment and simulations. 

PMID- 24588165
TI  - Probing the electronic structure and Au-C chemical bonding in AuC2(-) and AuC2
      using high-resolution photoelectron spectroscopy.
AB  - We report photoelectron spectroscopy (PES) and high-resolution PE imaging of
      AuC2(-) at a wide range of photon energies. The ground state of AuC2(-) is found
      to be linear (Cinfinityv, (1)Sigma(+)) with a
      ...8pi(4)4delta(4)17sigma(2)9pi(4)18sigma(2) valence configuration. Detachments
      from all the five valence orbitals of the ground state of AuC2(-) are observed at
      193 nm. High-resolution PE images are obtained in the energy range from 830 to
      330 nm, revealing complicated vibronic structures from electron detachment of the
      18sigma, 9pi, and 17sigma orbitals. Detachment from the 18sigma orbital results
      in the (2)Sigma(+) ground state of neutral AuC2, which, however, is bent due to
      strong vibronic coupling with the nearby (2)Pi state from detachment of a 9pi
      electron. The (2)Sigma(+)-(2)Pi vibronic and spin-orbit coupling results in
      complicated vibronic structures for the (2)Sigma(+) and (2)Pi3/2 states with
      extensive bending excitations. The electron affinity of AuC2 is measured
      accurately to be 3.2192(7) eV with a ground state bending frequency of 195(6) cm(
      1). The first excited state ((2)A') of AuC2, corresponding to the (2)Pi3/2 state
      at the linear geometry, is only 0.0021 eV above the ground state ((2)A') and has
      a bending frequency of 207(6) cm(-1). The (2)Pi1/2 state, 0.2291 eV above the
      ground state, is linear with little geometry change relative to the anion ground
      state. The detachment of the 17sigma orbital also results in complicated vibronic
      structures, suggesting again a bent state due to possible vibronic coupling with
      the lower (2)Pi state. The spectrum at 193 nm shows the presence of a minor
      species with less than 2% intensity relative to the ground state of AuC2(-). High
      resolution data of the minor species reveal several vibrational progressions in
      the Au-C stretching mode, which are assigned to be from the metastable (3)Pi2,1,0
      spin-orbit excited states of AuC2(-) to the (2)Pi3/2,1/2 spin-orbit states of
      neutral AuC2. The spin-orbit splittings of the (3)Pi and (2)Pi states are
      accurately measured at the linear geometry. The current study provides a wealth
      of electronic structure information about AuC2(-) and AuC2, which are ideal
      systems to investigate the strong Sigma-Pi and spin-orbit vibronic couplings.

PMID- 24588166
TI  - Comparison of the interactions in the rare gas hydride and Group 2 metal hydride
      anions.
AB  - We study both the rare gas hydride anions, RG-H(-) (RG = He-Rn) and Group 2
      (Group IIa) metal hydride anions, MIIaH(-) (MIIa = Be-Ra), calculating potential
      energy curves at the CCSD(T) level with augmented quadruple and quintuple basis
      sets, and extrapolating the results to the basis set limit. We report
      spectroscopic parameters obtained from these curves; additionally, we study the
      Be-He complex. While the RG-H(-) and Be-He species are weakly bound, we show
      that, as with the previously studied BeH(-) and MgH(-) species, the other MIIaH(
      ) species are strongly bound, despite the interactions nominally also being
      between two closed shell species: M(ns(2)) and H(-)(1s(2)). We gain insight into
      the interactions using contour plots of the electron density changes and
      population analyses. For both series, the calculated dissociation energy is
      significantly less than the ion/induced-dipole attraction term, confirming that
      electron repulsion is important in these species; this effect is more dramatic
      for the MIIaH(-) species than for RG-H(-). Our analyses lead us to conclude that
      the stronger interaction in the case of the MIIaH(-) species arises from sp and
      spd hybridization, which allows electron density on the MIIa atom to move away
      from the incoming H(-). 

PMID- 24588167
TI  - Quantum optimal control pathways of ozone isomerization dynamics subject to
      competing dissociation: a two-state one-dimensional model.
AB  - We construct a two-state one-dimensional reaction-path model for ozone open ->
      cyclic isomerization dynamics. The model is based on the intrinsic reaction
      coordinate connecting the cyclic and open isomers with the O2 + O asymptote on
      the ground-state (1)A(') potential energy surface obtained with the high-level ab
      initio method. Using this two-state model time-dependent wave packet optimal
      control simulations are carried out. Two possible pathways are identified along
      with their respective band-limited optimal control fields; for pathway 1 the wave
      packet initially associated with the open isomer is first pumped into a shallow
      well on the excited electronic state potential curve and then driven back to the
      ground electronic state to form the cyclic isomer, whereas for pathway 2 the
      corresponding wave packet is excited directly to the primary well of the excited
      state potential curve. The simulations reveal that the optimal field for pathway
      1 produces a final yield of nearly 100% with substantially smaller intensity than
      that obtained in a previous study [Y. Kurosaki, M. Artamonov, T.-S. Ho, and H.
      Rabitz, J. Chem. Phys. 131, 044306 (2009)] using a single-state one-dimensional
      model. Pathway 2, due to its strong coupling to the dissociation channel, is less
      effective than pathway 1. The simulations also show that nonlinear field effects
      due to molecular polarizability and hyperpolarizability are small for pathway 1
      but could become significant for pathway 2 because much higher field intensity is
      involved in the latter. The results suggest that a practical control may be
      feasible with the aid of a few lowly excited electronic states for ozone
      isomerization. 

PMID- 24588168
TI  - Quantum theory of atoms in molecules/charge-charge flux-dipole flux models for
      fundamental vibrational intensity changes on H-bond formation of water and
      hydrogen fluoride.
AB  - The Quantum Theory of Atoms In Molecules/Charge-Charge Flux-Dipole Flux
      (QTAIM/CCFDF) model has been used to investigate the electronic structure
      variations associated with intensity changes on dimerization for the vibrations
      of the water and hydrogen fluoride dimers as well as in the water-hydrogen
      fluoride complex. QCISD/cc-pVTZ wave functions applied in the QTAIM/CCFDF model
      accurately provide the fundamental band intensities of water and its dimer
      predicting symmetric and antisymmetric stretching intensity increases for the
      donor unit of 159 and 47 km mol(-1) on H-bond formation compared with the
      experimental values of 141 and 53 km mol(-1). The symmetric stretching of the
      proton donor water in the dimer has intensity contributions parallel and
      perpendicular to its C2v axis. The largest calculated increase of 107 km mol(-1)
      is perpendicular to this axis and owes to equilibrium atomic charge displacements
      on vibration. Charge flux decreases occurring parallel and perpendicular to this
      axis result in 42 and 40 km mol(-1) total intensity increases for the symmetric
      and antisymmetric stretches, respectively. These decreases in charge flux result
      in intensity enhancements because of the interaction contributions to the
      intensities between charge flux and the other quantities. Even though dipole flux
      contributions are much smaller than the charge and charge flux ones in both
      monomer and dimer water they are important for calculating the total intensity
      values for their stretching vibrations since the charge-charge flux interaction
      term cancels the charge and charge flux contributions. The QTAIM/CCFDF hydrogen
      bonded stretching intensity strengthening of 321 km mol(-1) on HF dimerization
      and 592 km mol(-1) on HF:H2O complexation can essentially be explained by charge,
      charge flux and their interaction cross term. Atomic contributions to the
      intensities are also calculated. The bridge hydrogen atomic contributions alone
      explain 145, 237, and 574 km mol(-1) of the H-bond stretching intensity
      enhancements for the water and HF dimers and their heterodimer compared with
      total increments of 149, 321, and 592 km mol(-1), respectively. 

PMID- 24588169
TI  - Effects of reactant rotation on the dynamics of the OH + CH4 -> H2O + CH3
      reaction: a six-dimensional study.
AB  - The dynamics of the hydrogen abstraction reaction between methane and hydroxyl
      radical is investigated using an initial state selected time-dependent wave
      packet method within a six-dimensional model. The ab initio calibrated global
      potential energy surface of Espinosa-Garcia and Corchado was used. Integral cross
      sections from several low-lying rotational states of both reactants have been
      obtained using the centrifugal sudden and J-shifting approximations. On the
      empirical potential energy surface, the rotational excitation of methane has
      little effect on the reaction cross section, but excited rotational states of OH
      inhibit the reactivity slightly. These results are rationalized with the newly
      proposed sudden vector projection model. 

PMID- 24588170
TI  - CO2 isolated line shapes by classical molecular dynamics simulations: influence
      of the intermolecular potential and comparison with new measurements.
AB  - Room temperature absorption spectra of various transitions of pure CO2 have been
      measured in a broad pressure range using a tunable diode-laser and a cavity ring
      down spectrometer, respectively, in the 1.6 MUm and 0.8 MUm regions. Their
      spectral shapes have been calculated by requantized classical molecular dynamics
      simulations. From the time-dependent auto-correlation function of the molecular
      dipole, including Doppler and collisional effects, spectral shapes are directly
      computed without the use of any adjusted parameter. Analysis of the spectra
      calculated using three different anisotropic intermolecular potentials shows that
      the shapes of pure CO2 lines, in terms of both the Lorentz widths and non-Voigt
      effects, slightly depend on the used potential. Comparisons between these ab
      initio calculations and the measured spectra show satisfactory agreement for all
      considered transitions (from J = 6 to J = 46). They also show that non-Voigt
      effects on the shape of CO2 transitions are almost independent of the rotational
      quantum number of the considered lines. 

PMID- 24588171
TI  - Theoretical study on the gas phase reaction of allyl chloride with hydroxyl
      radical.
AB  - The reaction of allyl chloride with the hydroxyl radical has been investigated on
      a sound theoretical basis. This is the first time to gain a conclusive insight
      into the reaction mechanism and kinetics for important pathways in detail. The
      reaction mechanism confirms that OH addition to the C=C double bond forms the
      chemically activated adducts, IM1 (CH2CHOHCH2Cl) and IM2 (CH2OHCHCH2Cl) via low
      barriers, and direct H-abstraction paths may also occur. Variational transition
      state model and multichannel RRKM theory are employed to calculate the
      temperature-, pressure-dependent rate constants. The calculated rate constants
      are in good agreement with the experimental data. At 100 Torr with He as bath
      gas, IM6 formed by collisional stabilization is the major products in the
      temperature range 200-600 K; the production of CH2CHCHCl via hydrogen
      abstractions becomes dominant at high temperatures (600-3000 K). 

PMID- 24588172
TI  - Line interference effects using a refined Robert-Bonamy formalism: the test case
      of the isotropic Raman spectra of autoperturbed N2.
AB  - A symmetrized version of the recently developed refined Robert-Bonamy formalism
      [Q. Ma, C. Boulet, and R. H. Tipping, J. Chem. Phys. 139, 034305 (2013)] is
      proposed. This model takes into account line coupling effects and hence allows
      the calculation of the off-diagonal elements of the relaxation matrix, without
      neglecting the rotational structure of the perturbing molecule. The formalism is
      applied to the isotropic Raman spectra of autoperturbed N2 for which a benchmark
      quantum relaxation matrix has recently been proposed. The consequences of the
      classical path approximation are carefully analyzed. Methods correcting for
      effects of inelasticity are considered. While in the right direction, these
      corrections appear to be too crude to provide off diagonal elements which would
      yield, via the sum rule, diagonal elements in good agreement with the quantum
      results. In order to overcome this difficulty, a re-normalization procedure is
      applied, which ensures that the off-diagonal elements do lead to the exact
      quantum diagonal elements. The agreement between the (re-normalized) semi
      classical and quantum relaxation matrices is excellent, at least for the Raman
      spectra of N2, opening the way to the analysis of more complex molecular systems.

PMID- 24588173
TI  - Theoretical study of photodetachment processes of anionic boron cluster. III.
      B(7)(-).
AB  - Photodetachment spectroscopy of B(7)(-) is theoretically studied in this paper.
      Calculated photodetachment bands are compared with the available experimental
      results and assigned to the vibronic structure of the electronic ground and
      excited states of the neutral B7 cluster. The complex structure of
      photodetachment bands is found to arise from many stable isomers of B(7)(-) of
      different symmetry point group. In this study we focus on three most stable
      isomers of B(7)(-) and examine their photodetachment bands. Extensive quantum
      chemistry calculations are carried out to establish the potential energy surfaces
      and the coupling surfaces of the electronic states of neutral B7 originating from
      each of the three isomers. A diabatic electronic ansatz is employed and the
      nuclear dynamics is studied both by time-independent and time-dependent quantum
      mechanical methods. Both agreements and discrepancies of the theoretical results
      with the experimental findings are discussed.

PMID- 24588174
TI  - Effect of laser spectral bandwidth on coherent control of resonance-enhanced
      multiphoton-ionization photoelectron spectroscopy.
AB  - The high-resolution (2 + 1) resonance-enhanced multiphoton-ionization
      photoelectron spectroscopy (REMPI-PS) can be obtained by measuring the
      photoelectron intensity at a given kinetic energy and scanning the single pi
      phase step position. In this paper, we further demonstrate that the high
      resolution (2 + 1) REMPI-PS cannot be achieved at any measured position of the
      kinetic energy by this measurement method, which is affected by the laser
      spectral bandwidth. We propose a double pi phase step modulation to eliminate the
      effect of the laser spectral bandwidth, and show the advantage of the double pi
      phase step modulation on achieving the high-resolution (2 + 1) REMPI-PS by
      considering the contributions involving on- and near-resonant three-photon
      excitation pathways. 

PMID- 24588175
TI  - Hydrogen migration dynamics in hydrated Al clusters: the Al17(-).H2O system as an
      example.
AB  - The Alm((-)).(H2O)n systems are known to undergo water splitting processes in the
      gas phase giving HkAlm(OH)k((-)).(H2O)n-k systems, which can generate H2. The
      migration of H atoms from one Al atom to another on the cluster's surface is of
      critical importance to the mechanism of the complete H2 production process. We
      have applied a combination of Molecular Dynamics and Rice-Ramsperger-Kassel
      Marcus theory including tunneling effects to study the gas-phase evolution of
      HAl17(OH)((-)), which can be considered a model system. First, we have performed
      an extensive search for local minima and the connecting saddle points using a
      density functional theory method. It is found that in the water-splitting process
      Al17((-)).(H2O) -> HAl17(OH)((-)), the H atom which bonds to the Al cluster
      losses rather quickly its excess energy, which is easily "absorbed" by the
      cluster because of its flexibility. This fact ultimately determines that long
      range hydrogen migration is not a very fast process and that, probably, tunneling
      only plays a secondary role in the migration dynamics, at least for moderate
      energies. Reduction of the total energy results in the process being very much
      slowed down. The consequences on the possible mechanisms of H2 generation from
      the interaction of Al clusters and water molecules are discussed.

PMID- 24588176
TI  - First-principles insights into interaction of CO, NO, and HCN with Ag8.
AB  - We use static as well as time-dependent first-principles computations to study
      interaction of the CO, NO, and HCN molecules with the Ag8 nanocluster. The many
      body based GW correction is applied for accurate description of the highest
      occupied (HOMO) and the lowest unoccupied (LUMO) molecular orbital levels. It is
      argued that the adsorption of these molecules changes the stable structure of Ag8
      from Td to the more chemically active D(2d) symmetry. We discuss that the CO, NO,
      and HCN molecules prefer to adsorb on the atom of the cluster with significant
      contribution to both HOMO and LUMO, for the accomplishment of the required charge
      transfers in the systems. The charge back donation is found to leave an excess
      energy of about 110 meV on the NO molecular bond, evidencing potential
      application of silver clusters for NO reduction. It is argued that CO and
      specially NO exhibit strong physical interaction with the silver cluster and
      hence significantly modify the electronic and optical properties of the system,
      while HCN makes very week physical bonds with the cluster. The optical absorption
      spectra of the Ag8 cluster before and after molecule adsorption are computed and
      a nontrivial red shift is observed in the NO and HCN adsorbed clusters.

PMID- 24588177
TI  - Accurate determination of the binding energy of the formic acid dimer: the
      importance of geometry relaxation.
AB  - The formic acid dimer in its C2h-symmetrical cyclic form is stabilized by two
      equivalent H-bonds. The currently accepted interaction energy is 18.75 kcal/mol
      whereas the experimental binding energy D0 value is only 14.22 +/-0.12 kcal/mol
      [F. Kollipost, R. W. Larsen, A. V. Domanskaya, M. Norenberg, and M. A. Suhm, J.
      Chem. Phys. 136, 151101 (2012)]. Calculation of the binding energies De and D0 at
      the CCSD(T) (Coupled Cluster with Single and Double excitations and perturbative
      Triple excitations)/CBS (Complete Basis Set) level of theory, utilizing
      CCSD(T)/CBS geometries and the frequencies of the dimer and monomer, reveals that
      there is a 3.2 kcal/mol difference between interaction energy and binding energy
      De, which results from (i) not relaxing the geometry of the monomers upon
      dissociation of the dimer and (ii) approximating CCSD(T) correlation effects with
      MP2. The most accurate CCSD(T)/CBS values obtained in this work are De = 15.55
      and D0 = 14.32 kcal/mol where the latter binding energy differs from the
      experimental value by 0.1 kcal/mol. The necessity of employing augmented VQZ and
      VPZ calculations and relaxing monomer geometries of H-bonded complexes upon
      dissociation to obtain reliable binding energies is emphasized. 

PMID- 24588178
TI  - Rovibrational energy transfer in the He-C3 collision: potential energy surface
      and bound states.
AB  - We present a four-dimensional potential energy surface (PES) for the collision of
      C3 with He. Ab initio calculations were carried out at the coupled-cluster level
      with single and double excitations and a perturbative treatment of triple
      excitations, using a quadruple-zeta basis set and mid-bond functions. The global
      minimum of the potential energy is found to be -26.9 cm(-1) and corresponds to an
      almost T-shaped structure of the van der Waals complex along with a slightly bent
      configuration of C3. This PES is used to determine the rovibrational energy
      levels of the He-C3 complex using the rigid monomer approximation (RMA) and the
      recently developed atom-rigid bender approach at the Close Coupling level (RB
      CC). The calculated dissociation energies are -9.56 cm(-1) and -9.73 cm(-1),
      respectively at the RMA and RB-CC levels. This is the first theoretical
      prediction of the bound levels of the He-C3 complex with the bending motion. 

PMID- 24588179
TI  - Reactive cluster model of metallic glasses.
AB  - Though discovered more than a half century ago metallic glasses remain a
      scientific enigma. Unlike crystalline metals, characterized by short, medium, and
      long-range order, in metallic glasses short and medium-range order persist,
      though long-range order is absent. This fact has prompted research to develop
      structural descriptions of metallic glasses. Among these are cluster-based models
      that attribute amorphous structure to the existence of clusters that are
      incommensurate with crystalline periodicity. Not addressed, however, are the
      chemical factors stabilizing these clusters and promoting their interconnections.
      We have found that glass formers are characterized by a rich cluster chemistry
      that above the glass transformation temperature promotes exchange as well as
      static and vibronic sharing of atoms between clusters. The vibronic mechanism
      induces correlated motions between neighboring clusters and we hypothesize that
      the distance over which these motions are correlated mediates metallic glass
      stability and influences critical cooling rates. 

PMID- 24588180
TI  - The random phase approximation applied to ice.
AB  - Standard density functionals without van der Waals interactions yield an
      unsatisfactory description of ice phases, specifically, high density phases
      occurring under pressure are too unstable compared to the common low density
      phase Ih observed at ambient conditions. Although the description is improved by
      using functionals that include van der Waals interactions, the errors in relative
      volumes remain sizable. Here we assess the random phase approximation (RPA) for
      the correlation energy and compare our results to experimental data as well as
      diffusion Monte Carlo data for ice. The RPA yields a very balanced description
      for all considered phases, approaching the accuracy of diffusion Monte Carlo in
      relative energies and volumes. This opens a route towards a concise description
      of molecular water phases on surfaces and in cavities. 

PMID- 24588181
TI  - Mass effect on the Soret coefficient in n-alkane mixtures.
AB  - We have determined the Soret coefficient of different equimolar and non equimolar
      n-alkane mixtures from measurements of the molecular diffusion and thermal
      diffusion coefficients. It is shown that equimolar mixtures behave as isotopic
      like mixtures in which only the mass effect contributes to the Soret effect. In
      non equimolar mixtures, a small linear dependence with the molar fraction is
      observed. Finally, we have obtained a new correlation, which allows the
      determination of the Soret coefficient of n-alkane mixtures using the data of
      viscosity, the thermal expansion coefficient of the pure components, and the
      density of the equimolar mixture. 

PMID- 24588182
TI  - Computer simulation of epitaxial nucleation of a crystal on a crystalline
      surface.
AB  - We present results of computer simulations of crystal nucleation on a crystalline
      surface, in the Lennard-Jones model. Motivated by the pioneering work of Turnbull
      and Vonnegut [Ind. Eng. Chem. 44, 1292 (1952)], we investigate the effects of a
      mismatch between the surface lattice constant and that of the bulk nucleating
      crystal. We find that the nucleation rate is maximum close to, but not exactly
      at, zero mismatch. The offset is due to the finite size of the nucleus. In
      agreement with a number of experiments, we find that even for large mismatches of
      10% or more, the formation of the crystal can be epitaxial, meaning that the
      crystals that nucleate have a fixed orientation with respect to the surface
      lattice. However, nucleation is not always epitaxial, and loss of epitaxy does
      affect how the rate varies with mismatch. The surface lattice strongly influences
      the nucleation rate. We show that the epitaxy observed in our simulations can be
      predicted using calculations of the potential energy between the surface and the
      first layer of the nucleating crystal, in the spirit of simple approaches such as
      that of Hillier and Ward [Phys. Rev. B 54, 14037 (1996)]. 

PMID- 24588183
TI  - Investigating vibrational anharmonic couplings in cyanide-bridged transition
      metal mixed valence complexes using two-dimensional infrared spectroscopy.
AB  - Using polarization-selective two-dimensional infrared (2D IR) spectroscopy, we
      measure anharmonic couplings and angles between the transition dipole moments of
      the four cyanide stretching (nuCN) vibrations found in
      [(NH3)5Ru(III)NCFe(II)(CN)5](-) (FeRu) dissolved in D2O and formamide and
      [(NC)5Fe(II)CNPt(IV)(NH3)4NCFe(II)(CN)5](4-) (FePtFe) dissolved in D2O. These
      cyanide-bridged transition metal complexes serve as model systems for studying
      the role of high frequency vibrational modes in ultrafast photoinduced charge
      transfer reactions. Here, we focus on the spectroscopy of the nuCN modes in the
      electronic ground state. The FTIR spectra of the nuCN modes of the bimetallic and
      trimetallic systems are strikingly different in terms of frequencies, amplitudes,
      and lineshapes. The experimental 2D IR spectra of FeRu and FePtFe and their fits
      reveal a set of weakly coupled anharmonic nuCN modes. The vibrational mode
      anharmonicities of the individual nuCN modes range from 14 to 28 cm(-1). The
      mixed-mode anharmonicities range from 2 to 14 cm(-1). In general, the bridging
      nuCN mode is most weakly coupled to the radial nuCN mode, which involves the
      terminal CN ligands. Measurement of the relative transition dipole moments of the
      four nuCN modes reveal that the FeRu molecule is almost linear in solution when
      dissolved in formamide, but it assumes a bent geometry when dissolved in D2O. The
      nuCN modes are modelled as bilinearly coupled anharmonic oscillators with an
      average coupling constant of 6 cm(-1). This study elucidates the role of the
      solvent in modulating the molecular geometry and the anharmonic vibrational
      couplings between the nuCN modes in cyanide-bridged transition metal mixed
      valence complexes. 

PMID- 24588184
TI  - Cross-nucleation between clathrate hydrate polymorphs: assessing the role of
      stability, growth rate, and structure matching.
AB  - Cross-nucleation is a phenomenon where a new crystal nucleates and grows upon the
      surface of a different polymorph. Previous studies indicate that faster growth
      rate of the new crystal is a necessary but not sufficient condition for cross
      nucleation. The thermodynamic stability of the different polymorphs can also
      affect cross-nucleation by modulating the rates of crystal growth. The interplay
      between thermodynamic stability of the polymorphs involved, the growth rate of
      the crystals, and the need for creation of an interfacial transition layer that
      seamlessly connects the two structures has not yet been fully elucidated.
      Predicting cross-nucleation is particularly challenging for clathrate hydrates,
      for which there are sometimes several polymorphs with similar stability and for
      which growth rates are not known. In this work, we use molecular dynamics
      simulations to investigate which factor (stability, growth rate, or formation of
      interfacial transition layer) controls cross-nucleation between the four known
      Frank-Kasper clathrate hydrate polymorphs: sI, sII, TS, and HS-I. We investigate
      the growth and cross-nucleation of these four hydrates filled with a set of guest
      molecules that produce different order of stabilities for the four crystal
      structures. We determine that the growth rate of sII clathrate is the fastest,
      followed by TS, HS-I, and sI. We find that cross-nucleation into or from sII
      clathrates is preceded by the formation of an interfacial transition layer at the
      seed crystal/liquid interface because sII does not share a crystal plane with sI,
      HS-I, or TS. Cross-nucleation between the latter three can occur seamlessly and
      is determined only by their growth rates. Our results indicate that nucleation of
      an interfacial transition layer between non-matching polymorphs can control cross
      nucleation or lack thereof under conditions of small driving force. Under
      conditions of sufficient supercooling clathrate hydrate polymorphs cross-nucleate
      into the fastest growing phase even if that new phase is less stable and does not
      share a common crystal plane with the initial polymorph. 

PMID- 24588186
TI  - The effect of the exchange-correlation functional on H2 dissociation on Ru(0001).
AB  - The specific reaction parameter (SRP) approach to density functional theory (DFT)
      has enabled a chemically accurate description of reactive scattering experiments
      for activated H2-metal systems (H2 + Cu(111) and Cu(100)), but its application
      has not yet resulted in a similarly accurate description of non-activated or
      weakly activated H2-metal systems. In this study, the effect of the choice of the
      exchange-correlation functional in DFT on the potential energy surface and
      dynamics of H2 dissociation on Ru(0001), a weakly activated system, is
      investigated. In total, full potential energy surfaces were calculated for over
      20 different functionals. The functionals investigated include functionals
      incorporating an approximate description of the van der Waals dispersion in the
      correlation functional (vdW-DF and vdW-DF2 functionals), as well as the revTPSS
      meta-GGA. With two of the functionals investigated here, which include vdW-DF and
      vdW-DF2 correlation, it has been possible to accurately reproduce molecular beam
      experiments on sticking of H2 and D2, as these functionals yield a reaction
      probability curve with an appropriate energy width. Diffraction probabilities
      computed with these two functionals are however too high compared to experimental
      diffraction probabilities, which are extrapolated from surface temperatures (Ts)
      ? 500 K to 0 K using a Debye-Waller model. Further research is needed to
      establish whether this constitutes a failure of the two candidate SRP functionals
      or a failure of the Debye-Waller model, the use of which can perhaps in future be
      avoided by performing calculations that include the effect of surface atom
      displacement or motion, and thereby of the experimental Ts. 

PMID- 24588187
TI  - Two charged states of hydrogen on the SrTiO3(001) surface.
AB  - The effects of hydrogen exposure on the electronic structure of two types of
      SrTiO3(001) surfaces, oxygen-deficient (OD) and nearly-vacancy-free (NVF)
      surfaces, were investigated with ultraviolet photoemission spectroscopy and
      nuclear reaction analysis. Upon molecular hydrogen exposure to the OD surface
      which reveals in-gap states at 1.3 eV below the Fermi level, the in-gap state
      intensity was reduced to half the initial value at a hydrogen coverage of 0.9 +/-
      0.7 * 10(14) cm(-2). On the NVF surface which has no in-gap state, on the other
      hand, atomic-hydrogen exposure induced in-gap states, and the hydrogen saturation
      coverage was evaluated to be 3.1 +/- 0.8 * 10(14) cm(-2). We argue that H is
      positively charged as H(~0.3 +) on the NVF surface by being coordinated to the O
      atom, whereas H is negatively charged as H(-) on the OD surface by occupying the
      oxygen vacancy site. The stability of H(-) at the oxygen vacancy site is
      discussed. 

PMID- 24588185
TI  - Exploring size and state dynamics in CdSe quantum dots using two-dimensional
      electronic spectroscopy.
AB  - Development of optoelectronic technologies based on quantum dots depends on
      measuring, optimizing, and ultimately predicting charge carrier dynamics in the
      nanocrystal. In such systems, size inhomogeneity and the photoexcited population
      distribution among various excitonic states have distinct effects on electron and
      hole relaxation, which are difficult to distinguish spectroscopically. Two
      dimensional electronic spectroscopy can help to untangle these effects by
      resolving excitation energy and subsequent nonlinear response in a single
      experiment. Using a filament-generated continuum as a pump and probe source, we
      collect two-dimensional spectra with sufficient spectral bandwidth to follow
      dynamics upon excitation of the lowest three optical transitions in a
      polydisperse ensemble of colloidal CdSe quantum dots. We first compare to prior
      transient absorption studies to confirm excitation-state-dependent dynamics such
      as increased surface-trapping upon excitation of hot electrons. Second, we
      demonstrate fast band-edge electron-hole pair solvation by ligand and phonon
      modes, as the ensemble relaxes to the photoluminescent state on a sub-picosecond
      time-scale. Third, we find that static disorder due to size polydispersity
      dominates the nonlinear response upon excitation into the hot electron manifold;
      this broadening mechanism stands in contrast to that of the band-edge exciton.
      Finally, we demonstrate excitation-energy dependent hot-carrier relaxation rates,
      and we describe how two-dimensional electronic spectroscopy can complement other
      transient nonlinear techniques. 

PMID- 24588188
TI  - Insight into the description of van der Waals forces for benzene adsorption on
      transition metal (111) surfaces.
AB  - Exploring the role of van der Waals (vdW) forces on the adsorption of molecules
      on extended metal surfaces has become possible in recent years thanks to exciting
      developments in density functional theory (DFT). Among these newly developed vdW
      inclusive methods, interatomic vdW approaches that account for the nonlocal
      screening within the bulk [V. G. Ruiz, W. Liu, E. Zojer, M. Scheffler, and A.
      Tkatchenko, Phys. Rev. Lett. 108, 146103 (2012)] and improved nonlocal
      functionals [J. Klimes, D. R. Bowler, and A. Michaelides, J. Phys.: Condens.
      Matter 22, 022201 (2010)] have emerged as promising candidates to account
      efficiently and accurately for the lack of long-range vdW forces in most popular
      DFT exchange-correlation functionals. Here we have used these two approaches to
      compute benzene adsorption on a range of close-packed (111) surfaces upon which
      it either physisorbs (Cu, Ag, and Au) or chemisorbs (Rh, Pd, Ir, and Pt). We have
      thoroughly compared the performance between the two classes of vdW-inclusive
      methods and when available compared the results obtained with experimental data.
      By examining the computed adsorption energies, equilibrium distances, and binding
      curves we conclude that both methods allow for an accurate treatment of
      adsorption at equilibrium adsorbate-substrate distances. To this end, explicit
      inclusion of electrodynamic screening in the interatomic vdW scheme and optimized
      exchange functionals in the case of nonlocal vdW density functionals is
      mandatory. Nevertheless, some discrepancies are found between these two classes
      of methods at large adsorbate-substrate separations. 

PMID- 24588189
TI  - Adsorption of CO2, N2, and CH4 in Cs-exchanged chabazite: a combination of van
      der Waals density functional theory calculations and experiment study.
AB  - The crucial role of dispersion force in correctly describing the adsorption of
      some typical small-size gas molecules (e.g., CO2, N2, and CH4) in ion-exchanged
      chabazites has been investigated at different levels of theory, including the
      standard density functional theory calculation using the Perdew, Burke, and
      Ernzerhof (PBE) exchange-correlation functional and van der Waals density
      functional theory (vdWDFT) calculations using different exchange-correlation
      models - vdW_DF2, optB86b, optB88, and optPBE. Our results show that the usage of
      different vdWDFT functionals does not significantly change the adsorption
      configuration or the profile of static charge rearrangement of the gas-chabazite
      complexes, in comparison with the results obtained using the PBE. The calculated
      values of adsorption enthalpy using different functionals are compared with our
      experimental results. We conclude that the incorporation of dispersion
      interaction is imperative to correctly predict the trend of adsorption enthalpy
      values, in terms of different gas molecules and Cs(+) cation densities in the
      adsorbents, even though the absolute values of adsorption enthalpy are
      overestimated by approximate 10 kJ/mol compared with experiments. 

PMID- 24588190
TI  - Yttrium-dispersed C60 fullerenes as high-capacity hydrogen storage medium.
AB  - Interaction between hydrogen molecules and functionalized C60 is investigated
      using density functional theory method. Unlike transition metal atoms that tend
      to cluster on the surface, C60 decorated with 12 Yttrium atoms on each of its 12
      pentagons is extremely stable and remarkably enhances the hydrogen adsorption
      capacity. Four H2 molecules can be chemisorbed on a single Y atom through well
      known Dewar-Chatt-Duncanson interaction. The nature of bonding is a weak
      physisorption for the fifth adsorbed H2 molecule. Consequently, the C60Y12
      complex with 60 hydrogen molecules has been demonstrated to lead to a hydrogen
      storage capacity of ~6.30 wt. %. 

PMID- 24588191
TI  - Ion transport in sub-5-nm graphene nanopores.
AB  - Graphene nanopore is a promising device for single molecule sensing, including
      DNA bases, as its single atom thickness provides high spatial resolution. To
      attain high sensitivity, the size of the molecule should be comparable to the
      pore diameter. However, when the pore diameter approaches the size of the
      molecule, ion properties and dynamics may deviate from the bulk values and
      continuum analysis may not be accurate. In this paper, we investigate the static
      and dynamic properties of ions with and without an external voltage drop in sub-5
      nm graphene nanopores using molecular dynamics simulations. Ion concentration in
      graphene nanopores sharply drops from the bulk concentration when the pore radius
      is smaller than 0.9 nm. Ion mobility in the pore is also smaller than bulk ion
      mobility due to the layered liquid structure in the pore-axial direction. Our
      results show that a continuum analysis can be appropriate when the pore radius is
      larger than 0.9 nm if pore conductivity is properly defined. Since many
      applications of graphene nanopores, such as DNA and protein sensing, involve ion
      transport, the results presented here will be useful not only in understanding
      the behavior of ion transport but also in designing bio-molecular sensors. 

PMID- 24588192
TI  - Modeling the construction of polymeric adsorbent media: effects of counter-ions
      on ligand immobilization and pore structure.
AB  - Molecular dynamics modeling and simulations are employed to study the effects of
      counter-ions on the dynamic spatial density distribution and total loading of
      immobilized ligands as well as on the pore structure of the resultant ion
      exchange chromatography adsorbent media. The results show that the porous
      adsorbent media formed by polymeric chain molecules involve transport mechanisms
      and steric resistances which cause the charged ligands and counter-ions not to
      follow stoichiometric distributions so that (i) a gradient in the local
      nonelectroneutrality occurs, (ii) non-uniform spatial density distributions of
      immobilized ligands and counter-ions are formed, and (iii) clouds of counter-ions
      outside the porous structure could be formed. The magnitude of these counter-ion
      effects depends on several characteristics associated with the size, structure,
      and valence of the counter-ions. Small spherical counter-ions with large valence
      encounter the least resistance to enter a porous structure and their effects
      result in the formation of small gradients in the local nonelectroneutrality,
      higher ligand loadings, and more uniform spatial density distributions of
      immobilized ligands, while the formation of exterior counter-ion clouds by these
      types of counter-ions is minimized. Counter-ions with lower valence charges,
      significantly larger sizes, and elongated shapes, encounter substantially greater
      steric resistances in entering a porous structure and lead to the formation of
      larger gradients in the local nonelectroneutrality, lower ligand loadings, and
      less uniform spatial density distributions of immobilized ligands, as well as
      substantial in size exterior counter-ion clouds. The effects of lower counter-ion
      valence on pore structure, local nonelectroneutrality, spatial ligand density
      distribution, and exterior counter-ion cloud formation are further enhanced by
      the increased size and structure of the counter-ion. Thus, the design,
      construction, and functionality of polymeric porous adsorbent media will
      significantly depend, for a given desirable ligand to be immobilized and
      represent the adsorption active sites, on the type of counter-ion that is used
      during the ligand immobilization process. Therefore, the molecular dynamics
      modeling and simulation approach presented in this work could contribute
      positively by representing an engineering science methodology to the design and
      construction of polymeric porous adsorbent media which could provide high
      intraparticle mass transfer and adsorption rates for the adsorbate biomolecules
      of interest which are desired to be separated by an adsorption process. 

PMID- 24588193
TI  - Dynamics of polymers: a mean-field theory.
AB  - We derive a general mean-field theory of inhomogeneous polymer dynamics; a theory
      whose form has been speculated and widely applied, but not heretofore derived.
      Our approach involves a functional integral representation of a Martin-Siggia
      Rose (MSR) type description of the exact many-chain dynamics. A saddle point
      approximation to the generating functional, involving conditions where the MSR
      action is stationary with respect to a collective density field rho and a
      conjugate MSR response field phi, produces the desired dynamical mean-field
      theory. Besides clarifying the proper structure of mean-field theory out of
      equilibrium, our results have implications for numerical studies of polymer
      dynamics involving hybrid particle-field simulation techniques such as the single
      chain in mean-field method. 

PMID- 24588194
TI  - Impacts of side chain and excess energy on the charge photogeneration dynamics of
      low-bandgap copolymer-fullerene blends.
AB  - Primary charge photogeneration dynamics in neat and fullerene-blended films of a
      pair of alternating benzo[1,2-b:4,5-b(')]dithiophene (BDT) and thieno[3,4
      b]thiophene (TT) copolymers are comparatively studied by using near-infrared,
      time-resolved absorption (TA) spectroscopy under low excitation photon fluence.
      PBDTTT-E and PBDTTT-C, differed merely in the respective TT-substituents of ester
      (-E) and carbonyl (-C), show distinctly different charge photogeneration
      dynamics. The pair of neat PBDTTT films show exciton lifetimes of ~0.1 ns and
      fluorescence quantum yields below 0.2%, as well as prominent excess-energy
      enhanced exciton dissociation. In addition, PBDTTT-C gives rise to >50% higher
      P(*+) yield than PBDTTT-E does irrespective to the excitation photon energy. Both
      PBDTTT-E:PC61BM and PBDTTT-C:PC61BM blends show subpicosecond exciton lifetimes
      and nearly unitary fluorescence quenching efficiency and, with respect to the
      former blend, the latter one shows substantially higher branching ratio of charge
      separated (CS) state over interfacial charge transfer (ICT) state, and hence more
      efficient exciton-to-CS conversion. For PBDTTT-C:PC61BM, the ultrafast charge
      dynamics clearly show the processes of ICT-CS interconversion and P(*+)
      migration, which are possibly influenced by the ICT excess energy. However, such
      processes are relatively indistinctive in the case of PBDTTT-E:PC61BM. The
      results strongly prove the importance of ICT dissociation in yielding free
      charges, and are discussed in terms of the film morphology and the precursory
      solution-phase macromolecular conformation. 

PMID- 24588195
TI  - Screening properties of four mesoscale smoothed charge models, with application
      to dissipative particle dynamics.
AB  - We extend our previous study [J. Chem. Phys. 138, 204907 (2013)] to quantify the
      screening properties of four mesoscale smoothed charge models used in dissipative
      particle dynamics. Using a combination of the hypernetted chain integral equation
      closure and the random phase approximation, we identify regions where the models
      exhibit a real-valued screening length, and the extent to which this agrees with
      the Debye length in the physical system. We find that the second moment of the
      smoothed charge distribution is a good predictor of this behaviour. We are thus
      able to recommend a consistent set of parameters for the models. 

PMID- 24588197
TI  - Twofold reentrant melting in a double-Gaussian fluid.
AB  - Isotropic pair potentials that are bounded at the origin have been proposed from
      time to time as models of the effective interaction between macromolecules of
      interest in the chemical physics of soft matter. We present a thorough study of
      the phase behavior of point particles interacting through a potential which
      combines a bounded short-range repulsion with a much weaker attraction at
      moderate distances, both of Gaussian shape. Notwithstanding the fact that the
      attraction acts as a small perturbation of the Gaussian-core model potential, the
      phase diagram of the double-Gaussian model (DGM) is far richer, showing two fluid
      phases and four distinct solid phases in the case that we have studied. Using
      free-energy calculations, the various regions of confluence of three distinct
      phases in the DGM system have all been characterized in detail. Moreover, two
      distinct lines of reentrant melting are found, and for each of them a rationale
      is provided in terms of the elastic properties of the solid phases. 

PMID- 24588196
TI  - Interplay between chain stiffness and excluded volume of semiflexible polymers
      confined in nanochannels.
AB  - The properties of channel-confined semiflexible polymers are determined by a
      complicated interplay of chain stiffness and excluded volume effects. Using
      Pruned-Enriched Rosenbluth Method (PERM) simulations, we study the equilibrium
      properties of channel-confined polymers by systematically controlling chain
      stiffness and excluded volume. Our calculations of chain extension and
      confinement free energy for freely jointed chains with and without excluded
      volume show excellent agreement with theoretical predictions. For ideal wormlike
      chains, the extension is seen to crossover from Odijk behavior in strong
      confinement to zero-stretching, bulk-like behavior in weak confinement. In
      contrast, for self-avoiding wormlike chains, we always observe that the linear
      scaling of the extension with the contour length is valid in the long-chain limit
      irrespective of the regime of confinement, owing to the coexistence of stiffness
      and excluded volume effects. We further propose that the long-chain limit for the
      extension corresponds to chain lengths wherein the projection of the end-to-end
      distance along the axis of the channel is nearly equal to the mean span parallel
      to the axis. For DNA in nanochannels, this limit was identified using PERM
      simulations out to molecular weights of more than 1 megabase pairs; the molecular
      weight of lambda-DNA is found to exhibit nearly asymptotic fractional extension
      for channels sizes used commonly in experiments. 

PMID- 24588198
TI  - Activation and deactivation of vibronic channels in intact phycocyanin rods.
AB  - We investigated the excitation modes of the light-harvesting protein phycocyanin
      (PC) from Thermosynechococcus vulcanus in the crystalline state using UV and near
      infrared Raman spectroscopy. The spectra revealed the absence of a hydrogen out
      of-plane wagging (HOOP) mode in the PC trimer, which suggests that the HOOP mode
      is activated in the intact PC rod, while it is not active in the PC trimer.
      Furthermore, in the PC trimer an intense mode at 984 cm(-1) is assigned to the C
      C stretching vibration while the mode at 454 cm(-1) is likely due to ethyl group
      torsion. In contrast, in the similar chromophore phytochromobilin the C5,10,15-D
      wag mode at 622 cm(-1) does not come from a downshift of the HOOP. Additionally,
      the absence of modes between 1200 and 1300 cm(-1) rules out functional
      monomerization. A correlation between phycocyanobilin (PCB) and phycoerythrobilin
      (PEB) suggests that the PCB cofactors of the PC trimer appear in a conformation
      similar to that of PEB. The conformation of the PC rod is consistent with that of
      the allophycocyanin (APC) trimer, and thus excitonic flow is facilitated between
      these two independent light-harvesting compounds. This excitonic flow from the PC
      rod to APC appears to be modulated by the vibration channels during HOOP wagging,
      C = C stretching, and the N-H rocking in-plan vibration. 

PMID- 24588199
TI  - Development of morphogen gradient: the role of dimension and discreteness.
AB  - The fundamental processes of biological development are governed by multiple
      signaling molecules that create non-uniform concentration profiles known as
      morphogen gradients. It is widely believed that the establishment of morphogen
      gradients is a result of complex processes that involve diffusion and degradation
      of locally produced signaling molecules. We developed a multi-dimensional
      discrete-state stochastic approach for investigating the corresponding reaction
      diffusion models. It provided a full analytical description for stationary
      profiles and for important dynamic properties such as local accumulation times,
      variances, and mean first-passage times. The role of discreteness in developing
      of morphogen gradients is analyzed by comparing with available continuum
      descriptions. It is found that the continuum models prediction about multiple
      time scales near the source region in two-dimensional and three-dimensional
      systems is not supported in our analysis. Using ideas that view the degradation
      process as an effective potential, the effect of dimensionality on establishment
      of morphogen gradients is also discussed. In addition, we investigated how these
      reaction-diffusion processes are modified with changing the size of the source
      region. 

PMID- 24588200
TI  - Ab initio investigation of the first hydration shell of protonated glycine.
AB  - The first hydration shell of the protonated glycine is built up using Monte Carlo
      multiple minimum conformational search analysis with the MMFFs force field. The
      potential energy surfaces of the protonated glycine and its hydration complexes
      with up to eight water molecules have been scanned and the energy-minimized
      structures are predicted using the ab initio calculations. First, three favorable
      structures of protonated glycine were determined, and the micro-hydration
      processes showed that water can significantly stabilize the unstable conformers,
      and then their first hydration shells were established. Finally, we found that
      seven water molecules are required to fully hydrate the first hydration shell for
      the most stable conformer of protonated glycine. In order to analyse the
      hydration process, the dominant hydration sites located around the ammonium and
      carboxyl groups are studied carefully and systemically. The results indicate
      that, water molecules hydrate the protonated glycine in an alternative dynamic
      hydration process which is driven by the competition between different hydration
      sites. The first three water molecules are strongly attached by the ammonium
      group, while only the fourth water molecule is attached by the carboxyl group in
      the ultimate first hydration shell of the protonated glycine. In addition, the
      first hydration shell model has predicted most identical structures and a
      reasonable accord in hydration energy and vibrational frequencies of the most
      stable conformer with the conductor-like polarizable continuum model. 

PMID- 24588201
TI  - The relation of maternal serum eNOS, NOSTRIN and ADMA levels with
      aetiopathogenesis of preeclampsia and/or intrauterine fetal growth restriction.
AB  - OBJECTIVE: The aim of present study was to assess the maternal serum endothelial
      nitric oxide synthase (eNOS), NOSTRIN (eNOS-trafficking inducer) and asymmetric
      dimethylarginine (ADMA) levels in pregnancies with intrauterine growth
      restriction (IUGR) in the presence or absence of preeclampsia and to compare the
      results with preeclamptic pregnant women with appropriate-for-gestational-age
      weight infants. PATIENTS AND METHODS: The study was performed on 65 normotensive
      pregnant women with isolated IUGR, 64 preeclamptic women with IUGR, 51
      preeclamptic women with normal intrauterine fetal growth and 65 healthy
      normotensive pregnant women with singleton uncomplicated pregnancies. Severe
      preeclampsia was defined as blood pressure> 160/110 mmHg with proteinuria> 5 g in
      a 24-h urinary protein excretion. IUGR were classified when the weight of the
      fetus was below the 10th centiles with disturbed placental function and abnormal
      ultrasonographic examination. The diagnosis was confirmed by the infant's weight
      at birth. The maternal serum eNOS, NOSTRIN and ADMA concentrations were
      determined using a sandwich enzyme-linked immunosorbent assays. RESULTS: There
      were no statistically significant differences in the eNOS and NOSTRIN levels
      between studied groups of women. Increased levels of ADMA in both preeclamptic
      groups and in women with pregnancies complicated by isolated IUGR were observed.
      CONCLUSIONS: Our results allow the conclusion that impaired NO bioavailability in
      pregnancies complicated by severe preeclampsia and/or IUGR result not from a
      reduced level or activity of eNOS or from its disturbed intracellular transport,
      but from increased ADMA levels, an endogenous inhibitor of the enzyme eNOS.

PMID- 24588202
TI  - Regioselective hydroacylation of 1,3-dienes by cobalt catalysis.
AB  - We describe a cobalt-catalyzed hydroacylation of 1,3-dienes with non-chelating
      aldehydes. Aromatic aldehydes provide 1,4-addition products as the major isomer,
      while aliphatic aldehydes favor 1,2-hydroacylation products. The kinetic profile
      supports an oxidative cyclization mechanism involving a cobaltacycle intermediate
      that undergoes transformation with high regio- and stereoselectivity. 

PMID- 24588203
TI  - Clinical and immunological profiles in 17 Japanese patients with drug-induced
      pemphigus studied at Kurume University.
AB  - BACKGROUND: Drug-induced pemphigus (DIP) shows clinical, histopathological and
      immunological features of pemphigus. However, little is known about immunological
      profiles in DIP. OBJECTIVES: To characterize clinical and immunological profiles
      in patients with DIP. METHODS: We studied 17 Japanese patients with DIP who were
      treated at Kurume University Hospital or who consulted from other hospitals
      between 1997 and 2012. Complicated diseases, clinical and histopathological
      manifestations, responsible drugs and findings in immunofluorescence, enzyme
      linked immunosorbent assays (ELISAs), immunoblotting (IB) and prognosis were
      analysed. RESULTS: Eight of the 17 patients with DIP showed pemphigus foliaceus
      like appearance, three showed pemphigus herpetiformis-like appearance, and six
      showed atypical bullous lesions. Responsible drugs were thiol-containing drugs in
      16 patients (bucillamine in nine cases, d-penicillamine in four cases, and
      cetapril, thiopronine and captopril in one patient each), and a nonthiol drug,
      sulfasalazine, in one patient. By ELISAs and/or IB analyses, nine patients
      reacted only with desmoglein 1 (Dsg1), four reacted with Dsg1 and Dsg3, and four
      showed no specific reactivity. By IB of normal human epidermal extracts, in
      addition to positive reactivity with Dsg1, four patients with no detectable
      malignancy showed paraneoplastic pemphigus-like reactivity with the 210-kDa
      envoplakin and the 190-kDa periplakin. Four cases showed anti-Dsg3 antibodies
      without mucosal lesions. While 11 cases recovered after discontinuation of the
      causative drugs, six patients had a very protracted or intractable disease
      course, and might develop true pemphigus. CONCLUSIONS: The present study
      indicated that the majority of the patients with DIP studied showed a pemphigus
      foliaceus-type phenotype with anti-Dsg1 autoantibodies, caused by thiol
      containing drugs.

PMID- 24588204
TI  - Viscous nature of the bond between adhering bacteria and substratum surfaces
      probed by atomic force microscopy.
AB  - Here we report on the viscous nature of the bond between adhering bacteria and a
      substratum surface. A tailor-made script was written for an atomic force
      microscope, that enabled a constant loading force of 1 or 5 nN to act for 30 s
      upon a bacterium compressed between a cantilever and a glass surface, while
      measuring its deformation. Time-dependent deformation was fitted to a one element
      Kelvin-Voigt analogue of the bond to yield a characteristic relaxation time and
      viscosity of the bond. Viscosities of streptococcal bonds were smaller (<20 kPa
      s) than those of staphylococcal bonds (>31 kPa s). Since staphylococci are
      relatively rich in extracellular polymeric substances, it can be inferred that
      the presence of extracellular polymeric substances yields the major contribution
      to the viscous response. The viscous nature of the bond between adhering bacteria
      and substratum surfaces provides the bacteria with more time to respond and
      protect themselves against external stresses. 

PMID- 24588205
TI  - Dawning of the epigenetic era in hereditary cancer.

PMID- 24588207
TI  - Imaging and quantification of endothelial cell loss in eye bank prepared DMEK
      grafts using trainable segmentation software.
AB  - PURPOSE: To improve accuracy and efficiency in quantifying the endothelial cell
      loss (ECL) in eye bank preparation of corneal endothelial grafts. METHODS: Eight
      cadaveric corneas were subjected to Descemet Membrane Endothelial Keratoplasty
      (DMEK) preparation. The endothelial surfaces were stained with a viability stain,
      calcein AM dye (CAM) and then captured by a digital camera. The ECL rates were
      quantified in these images by three separate readers using trainable
      segmentation, a plug-in feature from the imaging software, Fiji. Images were also
      analyzed by Adobe Photoshop for comparison. Mean times required to process the
      images were measured between the two modalities. RESULTS: The mean ECL (with
      standard deviation) as analyzed by Fiji was 22.5% (6.5%) and Adobe was 18.7%
      (7.0%; p = 0.04). The mean time required to process the images through the two
      different imaging methods was 19.9 min (7.5) for Fiji and 23.4 min (12.9) for
      Adobe (p = 0.17). CONCLUSIONS: Establishing an accurate, efficient and
      reproducible means of quantifying ECL in graft preparation and surgical
      techniques can provide insight to the safety, long-term potential of the graft
      tissues as well as provide a quality control measure for eye banks and surgeons.
      Trainable segmentation in Fiji software using CAM is a novel approach to
      measuring ECL that captured a statistically significantly higher percentage of
      ECL comparable to Adobe and was more accurate in standardized testing.
      Interestingly, ECL as determined using both methods in eye bank-prepared DMEK
      grafts exceeded 18% on average.

PMID- 24588206
TI  - Actions and interactions of alcohol and transforming growth factor beta1 on
      prepubertal hypothalamic gonadotropin-releasing hormone.
AB  - BACKGROUND: Alcohol (ALC) diminishes gonadotropin-releasing hormone (GnRH)
      secretion and delays puberty. Glial transforming growth factor beta1 (TGFbeta1)
      plays a role in glial-neuronal communications facilitating prepubertal GnRH
      secretion. We assessed the effects of acute ALC administration on TGFbeta1
      induced GnRH gene expression in the brain preoptic area (POA) and release of the
      peptide from the medial basal hypothalamus (MBH). Furthermore, we assessed
      actions and interactions of TGFbeta1 and ALC on an adhesion/signaling gene family
      involved in glial-neuronal communications. METHODS: Prepubertal female rats were
      administered ALC or water via gastric gavage at 7:30 am. At 9:00 am, saline or
      TGFbeta1 (100 ng/3 MUl) was administered into the third ventricle. At 3:00 pm,
      the POA was removed and frozen for gene expression analysis and repeated for
      protein assessments. In another experiment, the MBH was removed from ALC-free
      rats. After equilibration, tissues were incubated in Locke's medium only or
      medium containing TGFbeta1 with or without 50 mM ALC for measurement of GnRH
      peptide released in vitro. RESULTS: TGFbeta1 induced GnRH gene expression in the
      POA, and this effect was blocked by ALC. We also described the presence and
      responsiveness of the TGFbeta1 receptor in the POA and showed that acute ALC
      exposure not only altered the TGFbeta1-induced increase in TGFbeta-R1 protein
      expression but also the activation of receptor-associated proteins, Smad2 and
      Smad3, key downstream components of the TGFbeta1 signaling pathway. Assessment of
      an adhesion/signaling family consisting of glial receptor protein tyrosine
      phosphatase beta and neuronal contactin-associated protein-1 (Caspr1) and
      contactin showed that the neuronal components were induced by TGFbeta1 and that
      ALC blocked these effects. Finally, TGFbeta1 was shown to induce release of the
      GnRH peptide in vitro, an action that was blocked by ALC. CONCLUSIONS: We have
      demonstrated glial-derived TGFbeta1 induces GnRH gene expression in the POA and
      stimulates release of the peptide from the MBH, actions necessary for driving the
      pubertal process. Importantly, ALC acted at both brain regions to block
      stimulatory effects of TGFbeta1. Furthermore, ALC altered neuronal components of
      an adhesion/signaling family previously shown to be expressed on GnRH neurons and
      implicated in glial-GnRH neuronal communications. These results further
      demonstrate detrimental effects of ALC at puberty.

PMID- 24588208
TI  - Development of a method to extract and purify target compounds from medicinal
      plants in a single step: online hyphenation of expanded bed adsorption
      chromatography and countercurrent chromatography.
AB  - Pure compounds extracted and purified from natural sources are crucial to lead
      discovery and drug screening. This study presents a novel two-dimensional
      hyphenation of expanded bed adsorption chromatography (EBAC) and high-speed
      countercurrent chromatography (HSCCC) for extraction and purification of target
      compounds from medicinal plants in a single step. The EBAC and HSCCC were
      hyphenated via a six-port injection valve as an interface. Fractionation of
      ingredients of Salvia miltiorrhiza and Rhizoma coptidis was performed on the
      hyphenated system to verify its efficacy. Two compounds were harvested from
      Salvia miltiorrhiza, one was 52.9 mg of salvianolic acid B with an over 95%
      purity and the other was 2.1 mg of rosmarinic acid with a 74% purity. Another two
      components were purified from Rhizoma coptidis, one was 4.6 mg of coptisine with
      a 98% purity and one was 4.1 mg of berberine with a 82% purity. The processing
      time was nearly 50% that of the multistep method. The results indicate that the
      present method is a rapid and green way to harvest targets from medicinal plants
      in a single step. 

PMID- 24588209
TI  - Evaluation of adrenal function in critically ill children.
AB  - OBJECTIVE: There is no consensus on adequate adrenal response to critical
      illness. We aimed to evaluate adrenal function in critically ill children and its
      association with clinical outcome. We hypothesized that salivary cortisol would
      be a more appropriate tool to evaluate adrenal function in critically ill
      children. METHODS: This was a prospective cohort study. The concentrations of
      serum total and salivary cortisol were measured in 34 critically ill children
      before and after stimulation with 250 MUg adrenocorticotropic hormone (ACTH), and
      values were compared to a control group of healthy children (n = 15). Association
      between outcome and adrenal insufficiency defined by an increment in serum
      cortisol <=250 nm (9 MUg/dl) post-ACTH was assessed. RESULTS: Serum total and
      salivary cortisol concentrations pre- and post-ACTH were significantly higher in
      patients, and they were correlated at baseline (r = 0.67; P < 0.0001) and after
      ACTH (r = 0.41; P = 0.02). The incidence of adrenal insufficiency was 32.3%. This
      group had higher Paediatric Risk of Mortality III score (P = 0.04) but Paediatric
      Logistic Organ Dysfunction and vasoactive inotropic scores, duration of
      mechanical ventilation and length of paediatric intensive care unit and hospital
      stay were not significantly different compared with those with an increment >250
      nm (9 MUg/dl) post-ACTH. An inverse correlation between salivary cortisol post
      ACTH and vasoactive inotropic score (r = -0.56; P = 0.0008) was observed. A
      salivary cortisol concentration post-ACTH of <=226 nm (8.2 MUg/dl) had a
      sensitivity of 79% and a specificity of 62% to discriminate need for vasoactive
      or inotropic support (area under receiver operating characteristic (ROC) curve
      0.74). CONCLUSION: Adrenal insufficiency defined by the 'delta criterion' was not
      associated with outcome. A post-ACTH salivary cortisol of <=226 nm (8.2 MUg/dl)
      may be suggestive of an insufficient adrenal response to critical illness.

PMID- 24588211
TI  - Semivolatile organic compounds in indoor air and settled dust in 30 French
      dwellings.
AB  - Semivolatile organic compounds (SVOCs) are ubiquitous contaminants in indoor
      environments, emanating from different sources and partitioning among several
      compartments, including the gas phase, airborne particles, and settled dust.
      Nevertheless, simultaneous measurements in the three compartments are rarely
      reported. In this study, we investigated indoor concentrations of a wide range of
      SVOCs in 30 French dwellings. In settled dust, 40 out of 57 target compounds were
      detected. The highest median concentrations were measured for phthalates and to a
      lesser extent for bisphenol A, synthetic musks, some pesticides, and PAHs. Di(2
      ethylhexyl)phthalate (DEHP) and diisononyl phthalate (DINP) were the most
      abundant compounds. A total of 34 target compounds were detected both in the gas
      phase and airborne particles. The highest concentrations were measured for
      diisobutyl phthalate (DiBP), diethyl phthalate (DEP), dibutyl phthalate (DBP),
      and synthetic musks in the gas phase and for DEHP, DiBP, DBP, and DINP in the
      airborne particles. This is the first study on the indoor concentrations of a
      wide range of SVOCs in settled dust, gas phase, and airborne particles collected
      simultaneously in each dwelling. 

PMID- 24588210
TI  - Transfusion of older stored blood worsens outcomes in canines depending on the
      presence and severity of pneumonia.
AB  - BACKGROUND: In experimental pneumonia we found that transfused older blood
      increased mortality and lung injury that was associated with increased in vivo
      hemolysis and elevated plasma cell-free hemoglobin (CFH), non-transferrin-bound
      iron (NTBI), and plasma labile iron (PLI) levels. In this study, we additionally
      analyze identically treated animals that received lower or higher bacterial
      doses. STUDY DESIGN AND METHODS: Two-year-old purpose-bred beagles (n = 48)
      challenged intrabronchially with Staphylococcus aureus (0 [n = 8], 1.0 * 10(9) [n
      = 8], 1.25 * 10(9) [n = 24], and >=1.5 * 10(9) [n = 8] colony-forming units/kg)
      were exchange transfused with either 7- or 42-day-old canine universal donor
      blood (80 mL/kg in four divided doses). RESULTS: The greater increases in CFH
      with older blood over days after exchange proved relatively independent of
      bacterial dose. The lesser increases in CFH observed with fresher blood were
      bacterial dose dependent potentially related to bacterial hemolysins. Without
      bacterial challenge, levels of CFH, NTBI, and PLI were significantly higher with
      older versus fresher blood transfusion but there was no significant measurable
      injury. With higher-dose bacterial challenge, the elevated NTBI and PLI levels
      declined more rapidly and to a greater extent after transfusion with older versus
      fresher blood, and older blood was associated with significantly worse shock,
      lung injury, and mortality. CONCLUSION: The augmented in vivo hemolysis of
      transfused older red blood cells (RBCs) appears to result in excess plasma CFH
      and iron release, which requires the presence of established infection to worsen
      outcome. These data suggest that transfused older RBCs increase the risks from
      infection in septic subjects.

PMID- 24588212
TI  - Reply: hormonally targeted therapy for women with lymphangioleiomyomatosis.

PMID- 24588213
TI  - Is there still a role for hormonal blockade in lymphangioleiomyomatosis?

PMID- 24588215
TI  - Phenotypic modulation of smooth muscle cells by chemical and mechanical cues of
      electrospun tecophilic/gelatin nanofibers.
AB  - The ability of mature smooth muscle cells (SMCs) to modulate their phenotype in
      response to environmental cues is a critical issue related to vascular diseases.
      A tissue engineered vascular graft shall promote the contractile phenotype of
      vascular SMCs. To this aim, Tecophilic/gelatin (TP/gel) was electrospun at
      different weight ratios of TP/gelatin (100:0, 70:30, 50:50, 30:70), leading to
      differences in biochemical and mechanical properties of the nanofibers which in
      turn influenced the phenotype of SMCs. Results indicated that both the substrate
      with higher ligand density and lower stiffness could enhance SMC contractility
      and reduce cell proliferation. However, observing the highest SMCs contractility
      on electrospun TP(70)/gel(30) among the composite scaffolds demonstrated
      stiffness as the most critical parameter. Due to conflicting effects of softness
      versus minor fraction of gelatin (reduced ligand density) within TP(70)/gel(30)
      fibers, a relatively high proliferation of SMCs was still observed on
      TP(70)/gel(30) scaffold. The surface of TP(70)/gel(30) scaffold was further
      modified through physical adsorption of gelatin molecules so as to increase the
      ligand density on its surface, whereby a functional vascular construct that
      promotes the contractile behavior of SMCs with low cell proliferation was
      developed. 

PMID- 24588216
TI  - Collaboration changes both the content and the structure of memory: Building the
      architecture of shared representations.
AB  - Memory research has primarily focused on how individuals form and maintain
      memories across time. However, less is known about how groups of people working
      together can create and maintain shared memories of the past. Recent studies have
      focused on understanding the processes behind the formation of such shared
      memories, but none has investigated the structure of shared memory. This study
      investigated the circumstances under which collaboration would influence the
      likelihood that participants come to share both a similar content and a similar
      organization of the past by aligning their individual representations into a
      shared rendering. We tested how the frequency and the timing of collaboration
      affect participants' retrieval organization, and how this in turn influences the
      formation of shared memory and its persistence over time. Across numerous
      foundational and novel analyses, we observed that as the size of the
      collaborative inhibition effect-a counterintuitive finding that collaboration
      reduces group recall-increased, so did the amount of shared memory and the shared
      organization of memories. These findings reveal the interconnected relationship
      between collaborative inhibition, retrieval disruption, shared memory, and shared
      organization. Together, these relationships have intriguing implications for
      research across a wide variety of domains, including the formation of collective
      memory, beliefs and attitudes, parent-child narratives and the development of
      autobiographical memory, and the emergence of shared representations in
      educational settings.

PMID- 24588217
TI  - In doubt and disorderly: Ambivalence promotes compensatory perceptions of order.
AB  - Ambivalence is a presumably unpleasant experience, and coming to terms with it is
      an intricate part of human existence. It is argued that ambivalent attitude
      holders cope with their ambivalence through compensatory perceptions of order. We
      first show that ambivalence leads to an increase in (visual) perceptions of order
      (Study 1). In Study 2 we conceptually replicate this finding by showing that
      ambivalence also increases belief in conspiracy theories, a cognitive form of
      order perception. Furthermore, this effect is mediated by the negative emotions
      that are elicited by ambivalence. In Study 3 we show that increased need for
      order is driving these effects: Affirmations of order cancel out the effect of
      ambivalence on perceptions of order. Theoretical as well as societal implications
      are discussed.

PMID- 24588218
TI  - Chemical communication of fear: A case of male-female asymmetry.
AB  - Previous research has documented sex differences in nonverbal communication. What
      has remained unknown is whether similar sex differences would exist with regard
      to olfactory communication via chemosignals, a relatively neglected nonverbal
      communication medium. Because women generally have a better sense of smell and
      greater sensitivity to emotional signals, we hypothesized that compared with male
      participants and relative to a neutral control condition, female participants
      would emulate the fearful state of the sender producing the chemosignals. Facial
      electromyography was used in a double-blind experiment to measure in the receiver
      a partial reproduction of the state of the sender, controlling for the moderating
      influence of the sex of the sender and receiver. The results indicated that only
      female participants emulated the fearful state of the sender. The present study
      revealed a boundary condition for effective chemosignaling by reporting
      behavioral evidence of sexual asymmetry in olfactory communication via
      chemosignals.

PMID- 24588220
TI  - Formation of self-assembled nanoplates via hydrogenation of epitaxial Pd film.
AB  - Understanding the relationship between the uptake of hydrogen gas and hydride
      phase formation and evolution in metal solids is a phenomenon of significant
      technological importance due to current development of hydrogen storage devices,
      sensors, and membranes. The performance of these devices is degraded by
      structural defect formation during incoherent metal-hydride phase transformation.
      In this work, atomic force and scanning electron microscopy reveal formation of
      nanoplates along the ?111? directions in a (111) epitaxial Pd film. These
      nanostructures are observed after high temperature and high pressure gas phase
      hydrogenation and cooling in ambient temperature. Transmission electron
      microsocpy (TEM) analysis of a posthydrogenated film did not show considerable
      plastic deformation. The size of the nanoplates increased with increasing Pd film
      thickness. A formation mechanism of nanoplates is proposed: cooling the sample
      reactor in ambient temperature after hydrogen loading induced formation of
      coherent or partially coherent beta-phase plates along {100} planes corresponding
      to minimum elastic energy of interaction between metal and hydride phases. 

PMID- 24588219
TI  - Human P450-like oxidation of diverse proton pump inhibitor drugs by 'gatekeeper'
      mutants of flavocytochrome P450 BM3.
AB  - Production of drug metabolites is one area where enzymatic conversion has
      significant advantages over synthetic chemistry. These high value products are
      complex to synthesize, but are increasingly important in drug safety testing. The
      vast majority of drugs are metabolized by cytochromes P450 (P450s), with
      oxidative transformations usually being highly regio- and stereo-selective. The
      PPIs (proton pump inhibitors) are drugs that are extensively metabolized by human
      P450s, producing diverse metabolites dependent on the specific substrate. In the
      present paper we show that single mutations (A82F and F87V) in the
      biotechnologically important Bacillus megaterium P450 BM3 enzyme cause major
      alterations in its substrate selectivity such that a set of PPI molecules become
      good substrates in these point mutants and in the F87V/A82F double mutant. The
      substrate specificity switch is analysed by drug binding, enzyme kinetics and
      organic product analysis to confirm new activities, and X-ray crystallography
      provides a structural basis for the binding of esomeprazole to the F87V/A82F
      enzyme. These studies confirm that such 'gatekeeper' mutations in P450 BM3
      produce major perturbations to its conformation and substrate selectivity,
      enabling novel P450 BM3 reactions typical of those performed by human P450s.
      Efficient transformation of several PPI drugs to human-like products by BM3
      variants provides new routes to production of these metabolites. 

PMID- 24588221
TI  - Ionic liquids at electrified interfaces.

PMID- 24588222
TI  - White matter involvement beyond the optic nerves in CRION as assessed by
      diffusion tensor imaging.
AB  - BACKGROUND: Chronic relapsing inflammatory optic neuropathy (CRION) is an
      inflammatory optic neuropathy, characterized by relapses and remissions in
      patients with normal brain and spinal magnetic resonance imaging (MRI).
      Discrepancy from other demyelinating diseases is important, and it is still
      uncertain whether CRION is restricted to the optic pathways or it affects other
      brain white matter (WM) structures. OBJECTIVE: To assess WM structure in patients
      with CRION by using diffusion tensor imaging (DTI). METHODS: DTI was performed in
      six CRION patients and six age- and sex-matched healthy controls on a 3 T
      scanner. Tract-based spatial statistics (TBSS) was used for voxelwise statistical
      analysis of DTI data. Fractional anisotropy (FA), mean diffusivity (MD), axial
      diffusivity (AD), radial diffusivity (RD) measures were obtained. RESULTS: TBSS
      analysis revealed two different patterns of WM alterations in patients with
      CRION. The optic chiasm and connected structures had significantly higher FA and
      lower RD, AD and MD in the patients than in the healthy controls. On the other
      hand, anterior frontal bundles of inferior fronto-occipital tracts, left uncinate
      fascicule and internal capsule showed decreased FA and increased RD. No
      correlation was found between the clinical variables and diffusion measures.
      CONCLUSION: WM appearing normal on brain MRI shows widespread abnormalities in a
      cohort of CRION patients as assessed by DTI.

PMID- 24588223
TI  - Combined GSTP1 and NQO1 germline polymorphisms in the susceptibility to Multiple
      Sclerosis.
AB  - Germline polymorphisms of detoxification genes could influence susceptibility to
      Multiple Sclerosis (MS). Glutathione-S-transferases (GSTs) and NAD(P)H: quinone
      oxidoreductase 1 (NQO1) are detoxifying enzymes involved in biotransformation of
      metabolites preventing cells from oxidative damage. In order to evaluate the
      possible contribution of the A313G GSTP1 inactivating polymorphism, alone and in
      combination with the C609T NQO1 genetic variant in MS susceptibility, we
      performed a case-control study consisting of 254 MS patients and 370 healthy
      donors. Genotypes were investigated using a new Real-Time PCR and PCR-RFLP
      assays. The GSTP1 polymorphism was evaluated in relation to patients'
      characteristics (clinical subtypes, age and gender) and the NQO1 gene status.
      GSTP1 genotype distribution was similar between cases and controls. Higher
      frequency of GSTP1 heterozygotes was observed in patients with relapsing
      remitting disease (RRMS) (p = 0.019), especially in those presenting a benign
      form (EDSS <= 2 after 10-15 years from the disease onset). Interestingly,
      genotype distribution analysis of combined GSTP1 and NQO1 polymorphisms revealed
      significantly higher frequency of GSTP1 heterozygous (A/G) and NQO1 variant
      genotypes (C/T and T/T) in patients as compared to the controls (p = 0.031). The
      increased incidence of combined GSTP1 and NQO1 variant genotypes in MS patients
      may suggest that defective function of detoxification enzymes might be an
      important determinant of susceptibility and clinical manifestation of the
      disease. Moreover, the results suggest a possible role for the GSTP1 heterozygous
      background in the development of RRMS.

PMID- 24588224
TI  - In utero and lactational exposure to a mixture of environmental contaminants
      detected in Canadian Arctic human populations alters retinoid levels in rat
      offspring with low margins of exposure.
AB  - Arctic inhabitants are highly exposed to persistent organic pollutants (POP),
      which may produce adverse health effects. This study characterized alterations in
      tissue retinoid (vitamin A) levels in rat offspring and their dams following in
      utero and lactational exposure to the Northern Contaminant Mixture (NCM), a
      mixture of 27 contaminants including polychlorinated biphenyls (PCB),
      organochlorine (OC) pesticides, and methylmercury (MeHg), present in maternal
      blood of the Canadian Arctic Inuit population. Further, effect levels for
      retinoid system alterations and other endpoints were compared to the Arctic Inuit
      population exposure and their interrelationships were assessed. Sprague-Dawley
      rat dams were dosed with NCM from gestational day 1 to postnatal day (PND) 23.
      Livers, kidneys and serum were obtained from offspring on PND35, PND77, and
      PND350 and their dams on PND30 for analysis of tissue retinoid levels, hepatic
      cytochrome P-450 (CYP) enzymes, and serum thyroid hormones. Benchmark doses were
      established for all endpoints, and a partial least-squares regression analysis
      was performed for NCM treatment, hepatic retinoid levels, CYP enzyme induction,
      and thyroid hormone levels, as well as body and liver weights. Hepatic retinoid
      levels were sensitive endpoints, with the most pronounced effects at PND35 though
      still apparent at PND350. The effects on tissue retinoid levels and changes in
      CYP enzyme activities, body and liver weights, and thyroid hormone levels were
      associated and likely driven by dioxin-like compounds in the mixture. Low margins
      of exposure were observed for all retinoid endpoints at PND35. These findings are
      important for health risk assessment of Canadian Arctic populations and further
      support the use of retinoid system analyses in testing of endocrine-system
      modulating compounds. 

PMID- 24588225
TI  - Toxic effects of lead on biochemical and histological alterations in green mussel
      (Perna viridis) induced by environmentally relevant concentrations.
AB  - Acute and chronic toxicity tests were conducted on green mussel (Perna viridis)
      to determine the adverse effects of lead (Pb). Exposure of organisms to acute
      toxicity test for 96 h and lethal concentration (LC(50)) was the endpoint of the
      test. Acute toxicity for 96-h LC(50) and 95% confidence intervals of P. viridis
      was 2.62 +/- 0.12 (2.62-3.24) mg/L Pb. Chronic toxicity tests revealed that
      survival of exposed organisms decreased with elevated exposure concentrations. No
      observed-effect concentration (NOEC) and lowest-observed-effect concentration
      (LOEC) were calculated based on survival of test organisms. Results of this study
      demonstrated an increase in toxicity in test organisms with rise in exposure time
      and concentration. In this study, histology and biochemical enzymes, namely,
      catalase, reduced glutathione, glutathione S-transferase, and lipid peroxides,
      were correlated with chronic value and survival endpoints of P. viridis after
      chronic exposure to Pb. Biochemical and histological responses to different
      concentrations of Pb were assessed and significant differences were observed
      between control and increasing exposure concentrations. Biomarker studies in
      internal organs confirmed that the observed changes are due to adverse effects of
      Pb. This assessment of toxicity was the first step to determining the seawater
      quality criteria for marine organisms.

PMID- 24588226
TI  - Exposure to low levels of jet-propulsion fuel impairs brainstem encoding of
      stimulus intensity.
AB  - Jet propulsion fuel-8 (JP-8) is a kerosene-based fuel that is used in military
      jets. The U.S. Armed Services and North Atlantic Treaty Organization countries
      adopted JP-8 as a standard fuel source and the U.S. military alone consumes more
      than 2.5 billion gallons annually. Preliminary epidemiologic data suggested that
      JP-8 may interact with noise to induce hearing loss, and animal studies revealed
      damage to presynaptic sensory cells in the cochlea. In the current study, Long
      Evans rats were divided into four experimental groups: control, noise only, JP-8
      only, and JP-8 + noise. A subototoxic level of JP-8 was used alone or in
      combination with a nondamaging level of noise. Functional and structural assays
      of the presynaptic sensory cells combined with neurophysiologic studies of the
      cochlear nerve revealed that peripheral auditory function was not affected by
      individual exposures and there was no effect when the exposures were combined.
      However, the central auditory nervous system exhibited impaired brainstem
      encoding of stimulus intensity. These findings may represent important and major
      shifts in the theoretical framework that governs current understanding of jet
      fuel and/or jet fuel + noise-induced ototoxicity. From an epidemiologic
      perspective, results indicate that jet fuel exposure may exert consequences on
      auditory function that may be more widespread and insidious than what was
      previously shown. It is possible that a large population of military personnel
      who are suffering from the effects of jet fuel exposure may be misidentified
      because they would exhibit normal hearing thresholds but harbor a "hidden"
      brainstem dysfunction. 

PMID- 24588227
TI  - Particles influence allergic responses in mice--role of gender and particle size.
AB  - Epidemiological evidence suggesting that exposure to traffic air pollution may
      enhance sensitization to common allergens in children is increasing, and animal
      studies support biological plausibility and causality. The effect of air
      pollution on respiratory symptoms was suggested to be gender dependent. Previous
      studies showed that allergy-promoting activity of polystyrene particles (PSP)
      increased with decreasing particle size after footpad injection of mice. The
      primary aim of this study was to confirm the influence of particle size on the
      immunoglobulin E (IgE)-promoting capacity of particles in an airway allergy
      model. A second aim was to examine whether the allergy-promoting capacity of
      particles was influenced by gender. Female and male mice were intranasally
      exposed to the allergen ovalbumin (OVA) with or without ultrafine, fine, or
      coarse PSP modeling the core of ambient air particles. After intranasal booster
      immunizations with OVA, serum levels of OVA-specific IgE antibodies, and also
      markers of airway inflammation and cellular responses in the lung-draining
      mediastinal lymph nodes (MLN), were determined. PSP of all sizes promoted
      allergic responses, measured as increased serum concentrations of OVA-specific
      IgE antibodies. Further, PSP produced eosinophilic airway inflammation and
      elevated MLN cell numbers as well as numerically reducing the percentage of
      regulatory T cells. Ultrafine PSP produced stronger allergic responses to OVA
      than fine and coarse PSP. Although PSP enhanced sensitization in both female and
      male mice, significantly higher IgE levels and numbers of eosinophils were
      observed in females than males. However, the allergy-promoting effect of PSP was
      apparently independent of gender. Thus, our data support the notion that ambient
      air particle pollution may affect development of allergy in both female and male
      individuals. 

PMID- 24588228
TI  - Learning effect and repeatability of automated kinetic perimetry in healthy
      participants.
AB  - PURPOSE: To evaluate the learning effect and repeatability of automated kinetic
      perimetry in inexperienced and experienced healthy young participants. METHODS:
      Forty-six eyes of 46 healthy participants (23 eyes of 23 participants in the
      inexperienced group and 23 eyes of 23 participants in the experienced group; mean
      age, 25.9 years) were enrolled in this prospective study. Automated kinetic
      perimetry was performed using the Octopus 900 perimeter with Goldmann stimuli
      III4e, I4e, I3e, I2e and I1e. The participants underwent testing at 14
      predetermined meridians for each stimulus with a stimulus velocity of 3 degrees
      /s. The learning effect was evaluated for kinetic sensitivity and test duration
      using three measurements. Repeatability was evaluated by calculating the mean
      square (MS) and coefficient of variance (CoV) of the kinetic sensitivity between
      the second and third measurements. RESULTS: A learning effect was seen only in
      the inexperienced group between the first and second measurements. The kinetic
      sensitivity for III4e and I4e increased by 1.5 degrees  (p < 0.01) and 1.1
      degrees  (p = 0.02), respectively, and the test duration decreased to 20.1
      seconds (p = 0.02). There was no demonstrated learning effect in the
      inexperienced and experienced groups between the second and third measurements.
      Regarding the repeatability in the inexperienced and experienced groups, the MS
      and CoV values of the kinetic sensitivity for I3e, I2e and I1e increased by a
      median of 1.2-2.7 degrees  (p < 0.01) and 1.6-13.6% (p < 0.01), respectively,
      compared with those of III4e and I4e. CONCLUSION: The results of the first
      measurement in the inexperienced participants require careful evaluation,
      especially for III4e and I4e measured in the peripheral areas. However, because
      III4e and I4e both showed good repeatability in inexperienced and experienced
      participants, automated kinetic perimetry may be suitable for measuring the
      peripheral area using higher stimulus intensities such as III4e and I4e.

PMID- 24588229
TI  - Influenced but unaware: social influence on alcohol drinking among social
      acquaintances.
AB  - BACKGROUND: Drinking partners may be influenced by each other's alcohol
      consumption. However, these effects have only been shown in artificially created
      social pairings and typically among same-sex young adults. Here, we test whether
      similarly strong influence effects occur among "real" pairs of social
      acquaintances (friends and partners) and whether people are aware of this
      influence on their alcohol consumption. METHODS: Forty-six pairs of social
      acquaintances aged between 19 and 60 years old participated in a between-subjects
      experiment, in a semi-naturalistic bar laboratory setting. One member of each
      pair (the confederate) was randomly selected and asked to consume only alcoholic
      (alcohol condition) or soft drinks (nonalcohol condition), while the pair
      completed a game together in a bar setting. The other participant (naive) was
      unaware of these drinking instructions. Postconsumption, we measured the extent
      to which naive participants believed that their partner had influenced their own
      drinking behavior. RESULTS: A large effect of condition on alcohol consumption
      was observed, chi2 (2) = 15.8, p < 0.001, Cramer's V = 0.59, whereby the number
      of alcoholic drinks selected by naive participants in the alcohol confederate
      condition was significantly greater than in the nonalcohol confederate condition.
      The majority of naive participants (81%) also tended to be unaware that their
      partner had influenced their alcohol consumption. CONCLUSIONS: Social
      acquaintances are influenced by each other's alcohol consumption and may not be
      aware of this influence on their behavior.

PMID- 24588230
TI  - Nodavirus-based biological container for targeted delivery system.
AB  - Biological containers such as virus-like particles (VLPs) have gained increasing
      interest in the fields of gene therapy and vaccine development. Several virus
      based materials have been studied, but the toxicity, biodistribution, and
      immunology of these systems still require extensive investigation. The specific
      goal of this review is to provide information about nodaviruses, which are
      causative infectious agents of insects and aquatic animals, but not humans. By
      understanding the structure and biophysical properties of such viruses, further
      chemical or genetic modification for novel nanocarriers could be developed.
      Therefore, their application for therapeutic purposes, particularly in humans, is
      of great interest.

PMID- 24588231
TI  - Biogenic gold nanoparticles: As a potential candidate for brain tumor directed
      drug delivery.
AB  - Gold nanoparticles have tremendous application in the area of nanotechnology that
      raises new possibility in the treatment of brain tumor. These nanoparticles can
      be used for selectively gaining access to tumor due to their small size and
      modifiability. Gold nanoparticles are functionalized with various molecules such
      as anticancer drug, transferrin and monoclonal antibody to produce nanocarriers.
      These nanocarriers have ability to deliver the drug at targeted site. Transferrin
      crosses the blood-brain barrier because of the receptor-mediated endocytosis. The
      monoclonal antibody facilitates the release of anticancer drug at targeted sites.
      This approach of delivery saves the normal cells surrounding the tumor. 

PMID- 24588232
TI  - Ready, aim, act.

PMID- 24588233
TI  - Needs assessment: collecting the evidence.
AB  - How nurse planners collect needs assessment data has an impact on the success of
      educational activities. Instead of traditional approaches, such as an annual
      needs assessment, the focus needs to shift to the desired outcomes of the
      activity and the evidence that exists to demonstrate learner need.

PMID- 24588234
TI  - End-of-life experiential learning for newly licensed nurses.
AB  - Many newly licensed nurses begin their careers with limited knowledge and
      experience in end-of-life care. Findings from a literature review and a learning
      needs assessment of newly licensed nurses at a comprehensive cancer center guided
      the development of an 8-hour educational program on end-of-life care. An
      experiential learning approach was used to foster confidence and develop
      knowledge and skills in delivery of end-of-life care by newly licensed nurses.

PMID- 24588235
TI  - Rankism in nursing and health care.
AB  - Professional development educators can frame their practice by understanding
      rankism from an organizational development framework. Forms and functions of
      rankism are presented with reference to the work of Robert Fuller.

PMID- 24588236
TI  - Using a board game to reinforce learning.
AB  - Experiential gaming strategies offer a variation on traditional learning. A board
      game was used to present synthesized content of fundamental catheter care
      concepts and reinforce evidence-based practices relevant to nursing. Board games
      are innovative educational tools that can enhance active learning.

PMID- 24588238
TI  - Shape control of electrodeposited copper films and nanostructures through
      additive effects.
AB  - The use of electrolyte additives to affect nanocrystallite shape and film
      morphology in electrodeposited copper films is presented. Linear sweep and cyclic
      voltammetry, atomic force microscopy (AFM), scanning electron microscopy (SEM),
      and X-ray diffraction (XRD) methods are employed to investigate the effects of
      alcohol additives and the organic additive malachite green (MG), on copper
      electrodeposited onto polycrystalline gold electrodes. The use of additives
      affects the deposition process by increasing cathodic peak potentials and
      decreasing corresponding peak currents. Copper films deposited from electrolyte
      solutions with additives show additive-specific nanostructure and crystallite
      morphology. Film analysis reveals a greater than five times reduction in both
      film roughness and grain size in the presence of even small concentrations of the
      additive MG. Use of MG results in the preferential electrodeposition of oriented,
      square pyramidal crystallites, while alcohol additives result in tetrahedral
      crystallite textures. These shape-controlled additive effects are supported by
      additive adsorption energy calculations, which indicate preferential
      interactions, and differential growth kinetics on different facets of the film's
      growing nanostructures during electrodeposition. This approach offers a new and
      cost-effective route to achieve shape-controlled surface nanostructure. 

PMID- 24588239
TI  - [Long-term outcomes at not-penetrating glaucoma surgery].
AB  - OBJECTIVE: To evaluate the long-term compensation and efficacy after non
      penetrating deep sclerectomy using different types of implants. METHODS: Patients
      were divided in 3 groups: deep sclerectomy without implant (DS): 34 eyes, deep
      sclerectomy with Staar implant (DS+STAAR): 31 eyes, deep sclerectomy with T-flux
      implant (DS+T): 27 eyes. Postoperatively was evaluated: IOP, therapy and
      efficacy. RESULTS: The data are described by the relative quantity, continuous
      data by median, 5th and 95th percentile, always in order of groups: DS; DS+STAAR;
      DS+T, resp. Age at the time of surgery was 65.6 (44.9; 77.9); 64.5 (44.8; 85.0);
      72.1 (51.8; 77.0) years. Follow-up period was 84 (36; 145); 96 (36; 141); 81 (36;
      134) months. IOP was 26 (20; 32); 26 (20; 34); 26 (21,34) mmHg postoperatively.
      IOP was 14 (4; 18); 14 (4; 22); 8 (2; 16) mmHg at 1 month postoperatively. IOP
      was 17 (13; 23); 17 (12; 21); 14 (12; 18) mmHg at 96 months. IOP was 18 (1; 20);
      18 (10; 22); 15 (13; 16) mmHg at 132 months. Completely without therapy were 0;
      7.1; 42.9 % of eyes at 120 months. Complete success rate was 0; 7.1; 18.2 % at 96
      months. Qualified success rate was 87.5; 89.5; 100 % at 96 months. CONCLUSION:
      Deep sclerectomy is a good surgical technique to reduce the IOP in patients with
      glaucoma. Use of T-flux implant provides the best results in our groups.

PMID- 24588240
TI  - [Management of uncontrolled secondary glaucoma with ExPRESS glaucoma minishunt
      implantation].
AB  - The aim of the study was to evaluate the decrease of intraocular pressure and
      reduction of local as well as total therapy by patients with uncontrolled
      secondary glaucoma after antiglaucomatous surgery with mini implant ExPRESS. From
      the total of 61 eyes with this implant, operated in our clinic between years 2009
      2012, were 20 patients (22 eyes) with secondary glaucoma. Of which 7 eyes with
      neovascular glaucoma, 4 eyes with posttraumatic, 6 eyes with postuveitic, 4 with
      postoperative and 1 patient with pseudo-exfoliative glaucoma. 10 patients were
      after pars plana vitrectomy. In our group of patients was proven significant
      reduction of IOP and reduction of local and total therapy after surgery with the
      implant ExPRESS.

PMID- 24588241
TI  - [Functional results of cryosurgical procedures in rhegmatogenous retinal
      detachment including macula region - our experience].
AB  - AIM: Aim of this study is to evaluate retrospectively functional results of
      cryosurgical treatment of uncomplicated, idiopathic rhegmatogenous retinal
      detachment including macula region in phakic patients operated on at the
      Department of Ophthalmology, Faculty Hospital, Palacky University, Olomouc, Czech
      Republic, E.U., during the period 2002 -2013, and to evaluate the significance of
      the macula detachment duration for the final visual acuity. METHODS: In the study
      group were included 56 eyes of 56 patients operated in the years 2003 - 2012 at
      the Department of Ophthalmology, Faculty Hospital, Palacky University, Olomouc.
      All patients were phakic and in all of them, the retinal detachment including the
      macula region was diagnosed. The mean follow-up period of the patients was 8,75
      months. The initial and final visual acuity testing were performed. Comparing the
      initial and final visual acuity we rated the level of the visual acuity change.
      The result was stated as improved, if the visual acuity improved by 1 or more
      lines on the ETDRS chart. The result was rated as stabilized, if the visual
      acuity remained the same or it changed by 1 line of the ETDRS chart only. The
      result was evaluated as worsened, if the visual acuity decreased by 1 or more
      lines of the ETDRS chart. In the followed-up group, the authors compared visual
      acuity levels in patients with the macula detachment duration 10 days and 11
      days. For the statistical evaluation of achieved results, the Mann - Whitney U
      test was used. RESULTS: The visual acuity improved in 49 (87 %), did not changed
      in 5 (9 %) and worsened in 2 (4 %) patients. The patients with macula detachment
      duration 10 days achieved statistically significant better visual acuity than
      patients with macula detachment duration 11 days. CONCLUSION: Patients with
      macula detachment duration 10 days have better prognosis for functional result
      than patients with macula detachment duration 11 days.

PMID- 24588242
TI  - [The relations of morphological and functional changes in children with retinal
      dystrophy disease].
AB  - PURPOSE: To characterize the correlation between functional and morphological
      changes in the retina in the retinal dystrophies in children. METHODS: In the
      group of six patients with selected types of retinal dystrophies was analysed the
      morphological findings obtained by the Optical coherence tomography (OCT) and
      their correlation with the electrophysiological findings. RESULTS: Typical
      morphological retinal changes visualised by OCT were confirmed in all examined
      patients and were in correlation with progressive loss of visual function
      (decrease of visual acuity, constriction of visual field or scotomas in visual
      field, colour vision defect, nyctalopia) and abnormal values of the
      electrophysiological findings. CONCLUSION: Optical coherence tomography and
      electrophysiological methods are essential in approaching patient with
      tapetoretinal dystrophies. Correlation of these findings enables us to make
      diagnose easier, to understand better the dynamic of the morfological and
      functional changes in these patients. It can also be implicated as prognostic
      indicators for visual progression in patients with retinal dystrophy and also in
      prevention by means of genetic methods.

PMID- 24588243
TI  - [Development of number of endothelial cells after cataract surgery performed by
      femtolaser in comparison to conventional phacoemulsification].
AB  - PURPOSE: Compare the effect of cataract surgery with conventional
      phacoemulsification and cataract surgery performed on the cornea assisted by
      femtolaser with the help of contactless endothelial microscope. THE GROUP OF
      PATIENTS AND METHODS: In each group there were 25 eyes (25 patients) after the
      cataract surgery with conventional phacoemulsification and 25 eyes (25 patients)
      after cataract surgery performed on the cornea assisted by femtolaser with the
      help of contactless endothelial microscope. The number of endothelial cells was
      measured preoperatively, 1 day, 1 week and 1 month after the surgery. RESULTS: We
      compared the loss of endothelial cells during 3 various periods. The first day
      after the surgery we noticed an average decrease in number of endothelial cells
      by 1, 1% in the group with femtosecond laser, in the group with conventional
      phacoemulsification we noticed an average decrease of 3, 8 %. The first week
      after the surgery we noticed an average decrease in number of endothelial cells
      by 4, 5 % in the group with femtosecond laser, in the group with conventional
      phacoemulsification we noticed on average decrease of 6, 2 %. One month after
      surgery we noticed on average decrease in number of endothelial cells by 5, 1 %
      in the group with femtosecond laser, in the group with conventional
      phacoemulsification we noticed on average decrease of 9, 3 %. The difference
      between the average values in both groups was not at any point statistically
      significant (indication of statistically significance was value of P < 0. 05).
      CONCLUSION: Cataract surgery performed on the cornea assisted by femtolaser
      reduces trauma of the cornea and it reduces the lost of endothelial cells in
      comparison to conventional phacoemulsification.

PMID- 24588244
TI  - [Conservative management options for thyroid disease induced diplopia].
AB  - AIM: To focus on the conservative management options for diplopia in patients
      with thyroid ophthalmopathy in the active and in the "wait-for-operation" stage
      of the disease. To evaluate the degree of patient knowledge about the treatment
      options for diplopia and about different types of occlusion. To identify patient
      preferences when selecting from various management options. MATERIALS AND
      METHODS: This prospective study included patients with thyroid ophthalmopathy and
      disturbing diplopia in the primary gaze position who were referred for further
      treatment at the Department of Ophthalmology from January 2010 to June 2012.
      Twenty five patients (16 women and 9 men) were included for this study during the
      observation period. At the beginning, the degree of patient knowledge about the
      treatment options for diplopia and about different types of occlusion was
      assessed. Subsequently, all patients were informed in detail about different
      types of black and semi-translucent occlusion. After stabilization of diplopia,
      Fresnel prism and prism spectacle glasses were tested. At follow-up visits,
      patient preferences were evaluated. RESULTS: Twenty patients were initially
      informed about monocular patching options by their doctor. Only twelve patients
      received more specific recommendations on how to cover the eye; in all cases non
      translucent plastic or tape patch was recommended. Only one patient used non
      translucent occlusion in daily life; ten patients used it occasionally during
      static activities. None of the patients was informed about semi-translucent
      occlusion possibilities. At follow-up after two to four months, 19 patients used
      semi-translucent occlusion in daily life (18 used semi-translucent tape, one used
      frosted lens). Only one patient continued to use non-translucent occlusion. Five
      patients used no occlusion and closed one eye when necessary. CONCLUSION:
      Strabismus surgery in patients with thyroid ophthalmopathy is recommended in the
      inactive phase of the disease. For patients with diplopia it could be very
      difficult to overcome the active phase of the disease. In our study, the vast
      majority of patients in this phase preferred semi-translucent occlusion to non
      translucent one.

PMID- 24588245
TI  - Lipopeptides from the tropical marine cyanobacterium Symploca sp.
AB  - A collection of the tropical marine cyanobacterium Symploca sp., collected near
      Kimbe Bay, Papua New Guinea, previously yielded several new metabolites including
      kimbeamides A-C, kimbelactone A, and tasihalide C. Investigations into a more
      polar cytotoxic fraction yielded three new lipopeptides, tasiamides C-E (1-3).
      The planar structures were deduced by 2D NMR spectroscopy and tandem mass
      spectrometry, and their absolute configurations were determined by a combination
      of Marfey's and chiral-phase GC-MS analysis. These new metabolites are similar to
      several previously isolated compounds, including tasiamide (4), grassystatins (5,
      6), and symplocin A, all of which were isolated from similar filamentous marine
      cyanobacteria. 

PMID- 24588246
TI  - Editorial: coeliac disease - pathogenesis, prognosis and management.

PMID- 24588247
TI  - Commentary: refractory coeliac disease - rigorous management revealing, or
      resulting in, rarity?

PMID- 24588248
TI  - Commentary: refractory coeliac disease - rigorous management revealing, or
      resulting in, rarity? Authors' reply.

PMID- 24588249
TI  - Commentary: assessing remission in coeliac disease - are deamidated gliadin
      peptide antibodies the answer?

PMID- 24588250
TI  - Letter: diet and relapse in Crohn's disease.

PMID- 24588251
TI  - Letter: metabolite monitoring for thiopurines in Crohn's disease - still not
      fully understood.

PMID- 24588252
TI  - Letter: coffee and chronic liver damage.

PMID- 24588253
TI  - Hospital wet mount examination for the presence of sperm in sexual assault cases
      is of questionable value.
AB  - Many protocols for the examination of sexual assault victims include the
      preparation of vaginal wet mount slides to determine whether sperm are present
      and if so, whether the sperm are motile. We have reviewed findings in 501 case
      reports to compare the efficiency of sperm detection on wet mounts to subsequent
      crime laboratory results of sperm searches on vaginal swabs. Sperm were detected
      on wet mounts in only 41% of cases in which sperm were detected in the crime
      laboratory. Motile sperm were observed in only 12% of cases reporting a 0-9 h
      postcoital interval; in three cases, motile sperm were seen at 15 h and beyond,
      indicating that motile sperm are not reliable evidence of a short postcoital
      interval. These findings demonstrate that wet mount examinations are of little
      value in guiding subsequent analyses in the crime laboratory or in corroborating
      other investigative aspects of the case.

PMID- 24588255
TI  - Attenuated total reflectance-FT-IR imaging for rapid and automated detection of
      gunshot residue.
AB  - An alternative approach for the nondestructive, rapid and selective detection of
      gunshot residue (GSR) was investigated. A cloth substrate containing GSR
      particles expelled during a firearm discharge was used as an analog for the
      clothing of a shooting victim or a suspect discharging a firearm. An established
      and efficient procedure for GSR collection (tape lifting) was utilized to recover
      GSR particles from the cloth substrate. Microscopic-attenuated total reflectance
      (ATR) Fourier transform (FT) infrared (IR) spectroscopic imaging rapidly and
      automatically scanned large areas of the tape collection substrate and detected
      varying morphologies (microscopic and macroscopic) and chemical compositions
      (organic and inorganic) of GSR. The "spectroscopic fingerprint" of each GSR type
      provided unique virbrational modes, which were not characteristic of the tape
      collection substrate or the cloth debris which was also recovered. ATR images
      (maps) targeted the detection of these unique chemical markers over the mapped
      area. The hues of the ATR images were determined by the intensity of the signal
      for the chemical marker of each analyte. The spatial resolution of the technique
      was determined to be 4.7 MUm. Therefore, all GSR particles sized 4.7 MUm or
      larger will be resolved and detected on the tape substrate using micro-ATR
      imaging. 

PMID- 24588256
TI  - Near-surface strain in icosahedra of binary metallic alloys: segregational versus
      intrinsic effects.
AB  - A systematic structural analysis of FePt, CuAu, and Au icosahedral nanoparticles
      is presented. The uncovered particles are prepared by inert gas condensation and
      thermally equilibrated through in-flight optical annealing. Aberration-corrected
      high-resolution transmission electron microscopy reveals that the crystal lattice
      is significantly expanded near the particle surface. These experimental findings
      are corroborated by molecular statics simulations that show that this near
      surface strain originates from both intrinsic strain due to the icosahedral
      structure and a partial segregation of the larger of the two alloy constituents
      to the particle surface. 

PMID- 24588254
TI  - Biobanks and personalized medicine.
AB  - We provide a mini-review of how biobanks can support clinical genetics in the era
      of personalized medicine. We discuss types of biobanks, including disease
      specific and general biobanks not focused on one disease. We present
      considerations in setting up a biobank, including consenting and governance,
      biospecimens, risk factor and related data, informatics, and linkage to
      electronic health records for phenotyping. We also discuss the uses of biobanks
      and ongoing considerations, including genotype-driven recruitment, investigations
      of gene-environment associations, and the re-use of data generated from studies.
      Finally, we present a brief discussion of some of the unresolved issues, such as
      return of research results and sustaining biobanks over time. In summary,
      carefully designed biobanks can provide critical research and infrastructure
      support for clinical genetics in the era of personalized medicine.

PMID- 24588257
TI  - Mycobacterium fortuitum infection in continuous subcutaneous insulin infusion
      sites.

PMID- 24588258
TI  - Flavonoids from the halophyte Apocynum venetum and their antifouling activities
      against marine biofilm-derived bacteria.
AB  - Eleven flavonoids were isolated from the leaves of the halophyte Apocynum
      venetum. Among them, the isolation of plumbocatechin A (1), 8-O-methylretusin (2)
      and kaempferol 3-O-(6"-O-acetyl)-beta-D-galactopyranoside (7) was reported for
      the first time from this plant. Their structures were identified by using
      spectral methods, including 2D NMR experiments, and confirmed by comparing with
      the literature data. In addition, the antifouling activities of these compounds
      against the marine fouling bacteria, Bacillus thuringiensis, Pseudoalteromonas
      elyakovii and Pseudomonas aeruginosa, have been evaluated in this article.

PMID- 24588259
TI  - Air impacts of increased natural gas acquisition, processing, and use: a critical
      review.
AB  - During the past decade, technological advancements in the United States and
      Canada have led to rapid and intensive development of many unconventional natural
      gas plays (e.g., shale gas, tight sand gas, coal-bed methane), raising concerns
      about environmental impacts. Here, we summarize the current understanding of
      local and regional air quality impacts of natural gas extraction, production, and
      use. Air emissions from the natural gas life cycle include greenhouse gases,
      ozone precursors (volatile organic compounds and nitrogen oxides), air toxics,
      and particulates. National and state regulators primarily use generic emission
      inventories to assess the climate, air quality, and health impacts of natural gas
      systems. These inventories rely on limited, incomplete, and sometimes outdated
      emission factors and activity data, based on few measurements. We discuss case
      studies for specific air impacts grouped by natural gas life cycle segment,
      summarize the potential benefits of using natural gas over other fossil fuels,
      and examine national and state emission regulations pertaining to natural gas
      systems. Finally, we highlight specific gaps in scientific knowledge and suggest
      that substantial additional measurements of air emissions from the natural gas
      life cycle are essential to understanding the impacts and benefits of this
      resource. 

PMID- 24588260
TI  - Monoamniotic twins discordant for body stalk anomaly.
AB  - Body stalk anomaly is a rare malformation. This anomaly in monozygotic twins is
      extremely unusual. We describe a case of monoamniotic pregnancy discordant for
      body stalk anomaly diagnosed at 11 weeks. Ultrasound showed a fetus with a large
      anterior abdominal wall defect, anomaly of the spine and no evidence of lower
      extremities and other with a normal morphology. As far as our concern, only three
      monoamniotic pregnancies discordant for this malformation were reported. Our case
      represents the fourth reported monoamniotic pregnancy discordant for body stalk
      anomaly with diagnosis made by ultrasound and the second diagnosed in the first
      trimester.

PMID- 24588262
TI  - Fresh approaches to antidepressant drug discovery.
AB  - INTRODUCTION: The success of antidepressant research has long been challenged by
      a limited mechanistic understanding of depression pathogenesis and antidepressant
      treatment response. Progress in this field has thereby consistently been hindered
      by a lack of novel conceptual approaches and sophisticated experimental
      techniques to dissect the highly intricate neurobiology of depression. Using
      fresh approaches to investigate the cellular and molecular mechanisms underlying
      depression will thus be vital for discovery of novel antidepressant targets.
      AREAS COVERED: This article provides an overview of some fundamental problems
      that depression research is currently facing and critically evaluates how these
      issues could be addressed by future research. It also discusses novel conceptual
      and technological advances in the field of neuroscience, particularly in regard
      to how they may help in providing unprecedented insight into the molecular
      mechanisms of depression pathogenesis. EXPERT OPINION: Although progress in
      antidepressant drug discovery has been limited over recent years, modern
      innovations in neuroscience, molecular biology, genetics and bioinformatics are
      just beginning to revolutionize depression research and to reveal novel and
      promising treatment targets. Integrating findings from a range of relevant
      experimental models and using the most advanced technology will be vital for the
      future success of antidepressant drug discovery.

PMID- 24588261
TI  - Becoming a Lunari or Taiyo expert: learned attention to parts drives holistic
      processing of faces.
AB  - Faces are processed holistically, but the locus of holistic processing remains
      unclear. We created two novel races of faces (Lunaris and Taiyos) to study how
      experience with face parts influences holistic processing. In Experiment 1,
      subjects individuated Lunaris wherein the top, bottom, or both face halves
      contained diagnostic information. Subjects who learned to attend to face parts
      exhibited no holistic processing. This suggests that individuation only leads to
      holistic processing when the whole face is attended. In Experiment 2, subjects
      individuated both Lunaris and Taiyos, with diagnostic information in
      complementary face halves of the two races. Holistic processing was measured with
      composites made of either diagnostic or nondiagnostic face parts. Holistic
      processing was only observed for composites made from diagnostic face parts,
      demonstrating that holistic processing can occur for diagnostic face parts that
      were never seen together. These results suggest that holistic processing is an
      expression of learned attention to diagnostic face parts.

PMID- 24588263
TI  - Physical and biochemical insights on DNA structures in artificial and living
      systems.
AB  - CONSPECTUS: Highly specific DNA base-pairing is the basis for both fulfilling its
      genetic role and constructing novel nanostructures and hybrid conjugates with
      inorganic nanomaterials (NMs). There exist many remarkable differences in the
      physical properties of single-stranded (ss) and double-stranded (ds) DNA, which
      play important roles in regulation of biological processes in nature. Rapid
      advances in nanoscience and nanotechnology pose new questions on how DNA and DNA
      structures interact with inorganic nanomaterials or cells and animals, which
      should be important for their biological and biomedical applications. In this
      Account, we intend to provide an overview on many facets of DNA and DNA
      structures in artificial and living systems, with the focus on their properties
      and functions at the interfaces of inorganic nanomaterials and biological
      systems. ssDNA, dsDNA, and DNA nanostructures interact with NMs in different
      ways. In particular, gold nanoparticles and graphene oxide exhibit strikingly
      different affinity toward ssDNA and dsDNA. Such binding differences can be
      coupled with optical properties of NMs. For example, DNA hybridization can
      effectively modulate the plasmonic and catalytic properties of gold
      nanoparticles. By exploitation of these interactions, there have been many ways
      for sensitive transduction of biomolecular recognition for various sensing
      applications. Alternatively, modulation of the properties of DNA and DNA
      structures with NMs has led to new tools for genetic analysis including
      genotyping and haplotyping. Self-assembled DNA nanostructures have emerged as a
      new type of NMs with pure biomolecules. These nanostructures can be designed in
      one, two, or three dimensions with various sizes, shapes, and geometries. They
      also have characteristics of uniform size, precise addressability, excellent
      water solubility, and biocompatibility. These nanostructures provide a new
      toolbox for biophysical studies with unparalleled advantages, for example, NMR
      based protein structure determination and single-molecule studies. Also
      importantly, DNA nanostructures have proven highly useful in various applications
      including biological detection, bioreactors, and nanomedicine. In particular, DNA
      nanostructures exhibit high cellular permeability, a property that is not
      available for ssDNA and dsDNA, which is required for their drug delivery
      applications. DNA and DNA structures can also form hybrids with inorganic NMs.
      Notably, DNA anchored at the interface of inorganic NMs behaves differently from
      that at the macroscopic interface. Several types of DNA-NM conjugates have
      exerted beneficial effects for bioassays and in vitro translation of proteins.
      Even more interestingly, hybrid nanoconjugates demonstrate distinct properties
      under the context of biological systems such as cultured cells or animal models.
      These unprecedented properties not only arouse great interest in studying such
      interfaces but also open new opportunities for numerous applications in
      artificial and living systems.

PMID- 24588264
TI  - The Ang-(1-7)/Mas-1 axis attenuates the expression and signalling of TGF-beta1
      induced by AngII in mouse skeletal muscle.
AB  - AngII (angiotensin II) induces pathological conditions such as fibrosis in
      skeletal muscle. In this process, AngII increases ROS (reactive oxygen species)
      and induces a biphasic phosphorylation of p38 MAPK (mitogen-activated protein
      kinase). In addition, AngII stimulates the expression and production of TGF
      (transforming growth factor)-beta1 via a mechanism dependent on ROS production
      mediated by NADPH oxidase (NOX) and p38 MAPK activation. In the present study, we
      investigated whether Ang-(1-7) [angiotensin-(1-7)], through the Mas-1 receptor,
      can counteract the signalling induced by AngII in mouse skeletal muscle and cause
      a decrease in the expression and further activity of TGF-beta1 in skeletal muscle
      cells. Our results show that Ang-(1-7) decreased the expression of TGF-beta1
      induced by AngII in a dose-dependent manner. In addition, we observed that Ang-(1
      7) prevented the increase in TGF-beta1 expression induced by AngII, ROS
      production dependent on NOX and the early phase of p38 MAPK phosphorylation.
      Interestingly, Ang-(1-7) also prevented the late phase of p38 MAPK
      phosphorylation, Smad-2 phosphorylation and Smad-4 nuclear translocation, an
      increase in transcriptional activity, as determined using the p3TP-lux reporter,
      and fibronectin levels, all of which are dependent on the TGF-beta1 levels
      induced by AngII. We also demonstrated that Ang-(1-7) prevented the increase in
      TGF-beta1, fibronectin and collagen content in the diaphragm of mice infused with
      AngII. All of these effects were reversed by the administration of A779,
      indicating the participation of Mas-1. In conclusion, our findings support the
      hypothesis that Ang-(1-7) decreases the expression and further biological
      activity of TGF-beta1 induced by AngII in vitro and in vivo. 

PMID- 24588265
TI  - Identification of hematopoietic progenitor cell donor characteristics predicting
      successful mobilization: results of an Italian multicenter study.
AB  - BACKGROUND: Peripheral blood (PB) hematopoietic progenitor cells (HPC) collected
      by apheresis are the first-choice source for allogeneic stem cell
      transplantation. The target HPC dose is usually considered to be 4 * 10(6) CD34+
      cells/kg of the recipient, but higher doses are required in reduced-intensity
      conditioning and haploidentical transplants. Thus, prolonged stimulation and
      repeated collections or failure to reach HPC target may occur, increasing risks
      for donors and recipients. We carried out a retrospective multicenter study on
      healthy donors, to identify donor variables which may correlate with HPC
      mobilization. STUDY DESIGN AND METHODS: HPC allogeneic donations from sibling and
      unrelated donors performed in two centers from 1995 to 2012 were analyzed. We
      defined a mobilization cutoff of 50 * 10(6) CD34+ cells/L and tested somatic
      variables, blood counts, and granulocyte-colony-stimulating factor (G-CSF) dose
      and molecular form. RESULTS: A total of 360 donors were analyzed (male, 201;
      female, 159; sibling, 348; unrelated, 12; median [range] age, 44.8 [13-80]
      years). Median peak CD34+ in PB was 54.4 * 10(6) /L (range, 5 * 10(6) -299 *
      10(6) ). By multivariate analysis, we identified the following variables to
      correlate with good mobilization: 1) male sex (p<0.0005); 2) younger age
      (p=0.007); 3) higher baseline (premobilization) white blood cell (WBC) count
      (p<0.0005); 4) higher G-CSF dosage (p<0.0005); and 5) use of lenograstim rather
      than filgrastim (p<0.002). CONCLUSION: In healthy donors it is possible to
      predict successful HPC mobilization by donor sex, age, WBC count, and G-CSF form
      and dose. Furthermore, based on these data, it may be possible, at least in
      parental setting, to modulate G-CSF dosage on the basis of donor characteristics.

PMID- 24588266
TI  - Tonometry in corneal edema after cataract surgery: rebound versus goldmann
      applanation tonometry.
AB  - PURPOSE: Goldmann applanation tonometry (GAT) is known to be influenced by
      corneal properties, whereas the effect of corneal edema on intraocular pressure
      (IOP) measurement using Rebound tonometry (RT) is not clear. In this study, IOP
      was measured before and after cataract surgery using GAT and RT to investigate
      differences between methods and the effect of postsurgical corneal edema.
      METHODS: Thirty patients with cataract were included in a prospective study. IOP
      was measured using GAT and RT (Icare PRO, Tiolat Oy, Finland) before and after
      one day of phacoemulsification. Central corneal thickness (CCT) was determined
      before and after surgery (Pentacam, Oculus, Germany). RESULTS: CCT increased
      significantly after surgery by 52.2 +/- 35.1 um (p < 0.0001). IOP values of GAT
      and RT were significantly correlated before surgery (r = 0.65, p < 0.0001) and
      after surgery (r = 0.94, p < 0.0001). No significant correlation of GAT and RT to
      CCT before surgery (GAT: r = 0.18, p = 0.36; RT: r = 0.03, p = 0.87) or after
      surgery (GAT: r = -0.08, p = 0.69; RT: r = 0.17, p = 0.37) was found. The mean
      difference between GAT and RT (GAT-RT) was -1.0 +/- 2.9 mmHg (range -6.2 to 6.4
      mmHg, p = 0.08) before surgery and -1.1 +/- 2.2 mmHg (range -5.1 to 4.8 mmHg, p =
      0.01) after surgery. Before surgery, a positive correlation of GAT-RT with mean
      IOP of both methods is apparent (r = 0.45, p = 0.01). After surgery, no such
      correlation was found (r = -0.08, p = 0.69). CONCLUSIONS: RT underestimates IOP
      in higher values and overestimates IOP in lower values compared to GAT before
      surgery. This is not apparent in eyes with corneal edema. Large differences
      between methods may be present in individual patients with and without corneal
      edema.

PMID- 24588267
TI  - A simulation study on OH-containing polyimide (HPI) and thermally rearranged
      polybenzoxazoles (TR-PBO): relationship between gas transport properties and free
      volume morphology.
AB  - Recently, high free volume polymer materials have been regarded as high potential
      candidates for gas transport/separation membranes, since the amount of free
      volume in polymeric membrane can improve the diffusivity and solubility of gas
      molecules. In this study, we focused on how local changes in polymer structure
      can affect the performance of a membrane at the molecular level. The transport
      behavior was theoretically analyzed, and then the differences in the amount and
      morphology of free volume were characterized. Finally, we suggested how the
      "evolution of microcavities" affects the gas transport properties of hydroxyl
      containing polyimide (HPI) and thermally rearranged (TR) polymers. In particular,
      using image analysis, we intuitively demonstrate the morphological difference
      between HPI and TR polymers that have been indirectly explained by experimental
      analyses using a wide-angle X-ray diffractometer (WAXD) and positron annihilation
      laser spectroscopy (PALS). Solubility results using the grand canonical Monte
      Carlo (GCMC) method showed marginal improvement in thermally rearranged
      polybenzoxazoles (TR-PBOs) from its precursor HPI, which is in good agreement
      with the experimental tendency. Moreover, higher diffusivities but lower
      selectivities of TR-PBO models compared with those of HPI models were observed,
      as reported experimentally. The difference in gas transport abilities between
      HPIs and TR-PBOs originates from the difference in their diffusion behavior, and
      this is strongly related to the free volume amount and morphology of polymeric
      materials. In addition to the higher amount of total free volume in TR-PBO, our
      image analysis revealed that TR-PBO has a higher amount of interconnected
      "hourglass-shaped free volume elements", which consist of larger and more
      elongated cavities with bottlenecks than the HPI model. In particular, the
      bottleneck diameters in the TR-PBO models are wider than those in the HPI models,
      enabling the larger gas molecules to diffuse through the cavities faster.
      However, the narrower and smaller bottleneck diameters in the HPI model can
      induce better selectivity for large gas molecules. 

PMID- 24588268
TI  - Gas-flow-induced reorientation to centimeter-sized two-dimensional colloidal
      single crystal of polystyrene particle.
AB  - Centimeter-sized two-dimensional (2D) colloidal single crystals of polystyrene
      (PS) particles were fabricated at the water/air interface by capillary-modulated
      self-assembly. Different from previous reports, in this work, emulsifier was used
      to facilitate the stress release during 2D colloidal crystal formation by
      adjusting the interparticle lateral interactions. With the assistance of
      compressed nitrogen flow, 2D hexagonal colloidal single crystals of centimeter
      size were obtained under appropriate emulsifier concentrations. A new method was
      also developed to transfer the 2D colloidal crystals from the air/water interface
      to the desired substrate without obvious disturbance. This new transferring
      method was proven not to be sensitive to surface wettability nor curvature, thus
      2D colloidal single crystals with large areas could be obtained on different
      kinds of substrate. 

PMID- 24588269
TI  - Biologically active eremophilane-type sesquiterpenes from Camarops sp., an
      endophytic fungus isolated from Alibertia macrophylla.
AB  - Two new eremophilane-type sesquiterpenes, xylarenones F (3) and G (4), have been
      isolated from solid substrate cultures of a Camarops sp. endophytic fungus
      isolated from Alibertia macrophylla, together with the known compounds
      xylarenones C (1) and D (2). The structures and relative configurations of 1-4
      were elucidated by extensive NMR and HRESIMS spectroscopic analysis. Due to their
      effects on the respiratory burst of neutrophils, which included inhibition of the
      reactive oxygen species production, these sesquiterpenes exhibited potential anti
      inflammatory and antioxidant properties. 

PMID- 24588271
TI  - A case of bacillary angiomatosis in a patient with pancreatic adenocarcinoma.

PMID- 24588272
TI  - The shape of basal cell carcinoma.

PMID- 24588270
TI  - Sleep quality and alcohol risk in college students: examining the moderating
      effects of drinking motives.
AB  - OBJECTIVE: Sleep problems and alcohol misuse are common issues experienced by
      college students that can have detrimental effects on overall health. Previous
      work indicates a strong relationship between poor sleep quality and alcohol risk
      in this population. This study explored the moderating effect of drinking motives
      in the relationship between global sleep quality and experience of alcohol
      related negative consequences. PARTICIPANTS: College students (N = 1,878) who
      reported past-month drinking. METHODS: Participants completed online surveys
      assessing sleep and alcohol-related behaviors. RESULTS: Poorer sleep quality and
      higher drinking motives (coping, conformity, and enhancement) predicted greater
      alcohol-related consequences, controlling for drinking. Further, coping motives
      moderated the relationship between sleep quality and consequences such that
      participants reporting poor sleep and high coping motives experienced heightened
      levels of consequences. CONCLUSIONS: These findings advance the understanding of
      the relationship between sleep problems and alcohol-related risk and provide
      implications for targeted campus-based health promotion interventions.

PMID- 24588273
TI  - Use of hair testing to determine methadone exposure in pediatric deaths.
AB  - A case of death attributed to methadone acute poisoning in an infant aged 11
      months is reported. A sudden infant death syndrome (SIDS) was suspected, whereas
      a traumatic cause of death was excluded regarding autopsy findings. Specimens
      were submitted to a large toxicological analysis, which included ethanol
      measurement by HS-GC-FID, a targeted screening for drugs of abuse and various
      prescription drug classes followed by quantification using UPLC-MS/MS methods.
      Methadone and its metabolite (EDDP) were detected in all the tested fluids, as
      well as in hair, with a blood concentration of methadone considered as lethal for
      children (73 ng/mL). The cause of death was determined to be acute "methadone
      poisoning", and the manner of death was "accidental". A discussion of the case
      circumstances, the difficulties with the interpretation of toxicological findings
      in children (blood concentration and hair testing), and the origin of exposure
      are discussed. 

PMID- 24588276
TI  - To tweet or not to tweet.

PMID- 24588274
TI  - Maternal and neonatal plasma microRNA biomarkers for fetal alcohol exposure in an
      ovine model.
AB  - BACKGROUND: Plasma or circulating miRNAs (cir miRNAs) have potential diagnostic
      value as biomarkers for a range of diseases. Based on observations that ethanol
      (EtOH) altered intracellular miRNAs during development, we tested the hypothesis
      that plasma miRNAs were biomarkers for maternal alcohol exposure, and for past in
      utero exposure, in the neonate. METHODS: Pregnant sheep were exposed to a binge
      model of EtOH consumption resulting in an average peak blood alcohol content of
      243 mg/dl, for a third-trimester-equivalent period from gestational day 4 (GD4)
      to GD132. MiRNA profiles were assessed by quantitative PCR analysis in plasma,
      erythrocyte, and leukocytes obtained from nonpregnant ewes, and plasma from
      pregnant ewes 24 hours following the last binge EtOH episode, and from newborn
      lambs, at birth on ~GD147. RESULTS: Pregnant ewe and newborn lamb cir miRNA
      profiles were similar to each other and different from nonpregnant female plasma,
      erythrocyte, or leukocyte miRNAs. Significant changes in cir miRNA profiles were
      observed in the EtOH-exposed ewe and, at birth, in the in utero, EtOH-exposed
      lamb. Cir miRNAs including miR-9, -15b, -19b, and -20a were sensitive and
      specific measures of EtOH exposure in both pregnant ewe and newborn lamb.
      Additionally, EtOH exposure altered guide-to-passenger strand cir miRNA ratios in
      the pregnant ewe, but not in the lamb. CONCLUSIONS: Shared profiles between
      pregnant dam and neonate suggest possible maternal-fetal miRNA transfer. Cir
      miRNAs are biomarkers for alcohol exposure during pregnancy, in both mother and
      neonate, and may constitute an important shared endocrine biomarker that is
      vulnerable to the maternal environment.

PMID- 24588275
TI  - Concordance between gambling disorder diagnoses in the DSM-IV and DSM-5: Results
      from the National Epidemiological Survey of Alcohol and Related Disorders.
AB  - The fifth edition of the Diagnostic and Statistic Manual for Mental Disorders
      (DSM-5) eliminates the committing illegal acts criterion and reduces the
      threshold for a diagnosis of gambling disorder to 4 of 9 criteria. This study
      compared the DSM-5 "4 of 9" classification system to the "5 of 10" DSM-IV system,
      as well as other permutations (i.e., just lowing the threshold to 4 criteria or
      just eliminating the illegal acts criterion) in 43,093 respondents to the
      National Epidemiological Survey of Alcohol and Related Conditions. Subgroups were
      analyzed to ascertain whether changes will impact differentially diagnoses based
      on gender, age, or race/ethnicity. In the full sample and each subpopulation,
      prevalence rates were higher when the DSM-5 classification system was employed
      relative to the DSM-IV system, but the hit rate between the two systems ranged
      from 99.80% to 99.96%. Across all gender, age, and racial/ethnic subgroups,
      specificity was greater than 99% when the DSM-5 system was employed relative to
      the DSM-IV system, and sensitivity was 100%. Results from this study suggest that
      eliminating the illegal acts criterion has little impact on diagnosis of gambling
      disorder, but lowering the threshold for diagnosis does increase the base rate in
      the general population and each subgroup, even though overall rates remain low
      and sensitivity and specificity are high.

PMID- 24588277
TI  - The effect of topical ointment on neonatal sepsis in preterm infants.
AB  - OBJECTIVE: To investigate the effects of topical ointment therapy on neonatal
      sepsis in premature infants. METHODS: A total of 197 premature infants<=34 weeks
      gestation were randomized to receive topical ointment (Aquaphor Original
      Emollient) or routine skin care group. Skin cultures were obtained on 3th, 7th
      and 14th day and blood cultures were obtained if sepsis was suspected clinically.
      Data included the maternal and neonatal characteristics, factors affecting the
      risk of sepsis and neonatal outcomes of both groups were collected. RESULTS:
      There were no significant differences in terms of gestational age, birth weight,
      gender, mode of delivery, multiple pregnancy and receiving antenatal
      corticosteroids between the study and control group. No statistically significant
      difference was found in the prevalence of sepsis, in the positive skin culture
      rates at any follow-up and in terms of the neonatal morbidities including patent
      ductus arteriosus and necrotizing enterocolitis between the groups. Although the
      rate of death was higher in the topical ointment group, no statistically
      significant difference was found between the groups. CONCLUSIONS: Our data
      suggests that applying topical ointment during the first 2 postnatal weeks did
      not affect the risk of neonatal sepsis in preterm infants, although it changed
      the bacterial flora on the skin compare to the routine care group.

PMID- 24588279
TI  - Chirality in thiolate-protected gold clusters.
AB  - Over recent years, research on thiolate-protected gold clusters Au(m)(SR)n has
      gained significant interest. Milestones were the successful determination of a
      series of crystal structures (Au102(SR)44, Au25(SR)18, Au38(SR)24, Au36(SR)24,
      and Au28(SR)20). For Au102(SR)44, Au38(SR)24, and Au28(SR)20, intrinsic chirality
      was found. Strong Cotton effects (circular dichroism, CD) of gold clusters
      protected by chiral ligands have been reported a long time ago, indicating the
      transfer of chiral information from the ligand into the cluster core. Our lab has
      done extensive studies on chiral thiolate-protected gold clusters, including
      those protected with chiral ligands. We demonstrated that vibrational circular
      dichroism can serve as a useful tool for the determination of conformation of the
      ligand on the surface of the cluster. The first reports on crystal structures of
      Au102(SR)44 and Au38(SR)24 revealed the intrinsic chirality of these clusters.
      Their chirality mainly arises from the arrangement of the ligands on the surface
      of the cluster cores. As achiral ligands are used to stabilize the clusters,
      racemic mixtures are obtained. However, the separation of the enantiomers by HPLC
      was demonstrated which enabled the measurement of their CD spectra. Thermally
      induced inversion allows determination of the activation parameters for their
      racemization. The inversion demonstrates that the gold-thiolate interface is
      anything but fixed; in contrast, it is rather flexible. This result is of
      fundamental interest and needs to be considered in future applications. A second
      line of our research is the selective introduction of chiral, bidentate ligands
      into the ligand layer of intrinsically chiral gold clusters. The ligand exchange
      reaction is highly diastereoselective. The bidentate ligand connects two of the
      protecting units on the cluster surface and thus effectively stabilizes the
      cluster against thermally induced inversion. A minor (but significant) influence
      of chiral ligands to the CD spectra of the clusters is observed. The studied
      system represents the first example of an intrinsically chiral gold cluster with
      a defined number of exchanged ligands, full control over their regio- and
      stereochemistry. The methodology allows for the selective preparation of mixed
      ligand cluster compounds and a thorough investigation of the influence of single
      ligands on the cluster's properties. Overall, the method enables even more
      detailed tailoring of properties. Still, central questions remain unanswered: (1)
      Is intrinsic chirality a ubiquitous feature of thiolate-protected gold clusters?
      (2) How does chirality transfer work? (3) What are the applications for chiral
      thiolate-protected gold clusters? In this Account, we summarize the main findings
      on chirality in thiolate-protected gold cluster of the past half decade. Emphasis
      is put on intrinsically chiral clusters and their structures, optical activity,
      and reactivity.

PMID- 24588278
TI  - Anomalous capacitive behaviors of graphene oxide based solid-state
      supercapacitors.
AB  - Substantial differences in charge storage mechanisms exist between dielectric
      capacitors (DCs) and electrochemical capacitors (ECs), resulting in orders of
      magnitude difference of stored charge density in them. However, if ionic
      diffusion, the major charge transport mechanism in ECs, is confined within
      nanoscale dimensions, the Helmholtz layers and diffusion layers will overlap,
      resulting in dismissible ionic diffusion. An interesting contradiction between
      appreciable energy density and unrecognizable ionic diffusion is observed in
      solid-state capacitors made from reduced graphene oxide films that challenge the
      fundamental charge storage mechanisms proposed in such devices. A new capacitive
      model is proposed, which combines the two distinct charge storage mechanisms of
      DCs and ECs, to explain the contradiction, of high storage capacity yet
      undetectable ionic diffusion, seen in graphene oxide based supercapacitors. 

PMID- 24588280
TI  - Letter: European Medicines Agency recommendations for allergic reactions to
      intravenous iron-containing medicines.

PMID- 24588281
TI  - Blockade of gap junction hemichannel protects secondary spinal cord injury from
      activated microglia-mediated glutamate exitoneurotoxicity.
AB  - We previously demonstrated that activated microglia release excessive glutamate
      through gap junction hemichannels and identified a novel gap junction hemichannel
      blocker, INI-0602, that was proven to penetrate the blood-brain barrier and be an
      effective treatment in mouse models of amyotrophic lateral sclerosis and
      Alzheimer disease. Spinal cord injury causes tissue damage in two successive
      waves. The initial injury is mechanical and directly causes primary tissue
      damage, which induces subsequent ischemia, inflammation, and neurotoxic factor
      release resulting in the secondary tissue damage. These lead to activation of
      glial cells. Activated glial cells such as microglia and astrocytes are common
      pathological observations in the damaged lesion. Activated microglia release
      glutamate, the major neurotoxic factor released into the extracellular space
      after neural injury, which causes neuronal death at high concentration. In the
      present study, we demonstrate that reduction of glutamate-mediated exitotoxicity
      via intraperitoneal administration of INI-0602 in the microenvironment of the
      injured spinal cord elicited neurobehavioral recovery and extensive suppression
      of glial scar formation by reducing secondary tissue damage. Further, this
      intervention stimulated anti-inflammatory cytokines, and subsequently elevated
      brain-derived neurotrophic factor. Thus, preventing microglial activation by a
      gap junction hemichannel blocker, INI-0602, may be a promising therapeutic
      strategy in spinal cord injury.

PMID- 24588282
TI  - Cytotoxic activity of two natural sesquiterpene lactones, isobutyroylplenolin and
      arnicolide D, on human colon cancer cell line HT-29.
AB  - In this study, we found that two sesquiterpene lactones, isobutyroylplenolin and
      arnicolide D, from Centipeda minima L. (Compositae) exerted stronger cytotoxic
      activity than cisplatin on the human colon carcinoma HT-29 cell line.
      Furthermore, the cytotoxicity of these two compounds on normal cells was weaker
      than that of cisplatin. Treatment with isobutyroylplenolin and arnicolide D
      increased the levels of intracellular reactive oxygen species and decreased the
      levels of nuclear factor-kappaB protein, resulting in cell cycle arrest in G1
      phase and apoptosis. We also discuss the difference in structure and activity
      between these two compounds. 

PMID- 24588283
TI  - The ageing Australian firefighter: an argument for age-based recruitment and
      fitness standards for urban fire services.
AB  - Currently, there is no enforcement of physical standards within Australian fire
      services post-recruitment, possibly leading to inappropriate fitness and body
      composition. This study evaluated the impacts of ageing on physical standards of
      Australian firefighters. Seventy-three firefighters from three different 10-year
      age groups [25-34 years (n = 27), 35-44 years (n = 27), 45-54 years (n = 19)]
      volunteered for physical testing using dual-energy X-ray analysis and existing
      fitness tests used for recruitment by an Australian fire service. Older (45-54
      years) participants demonstrated significantly poorer physical standards compared
      with younger participants including cardiovascular fitness (p < 0.05), strength
      (p = 0.001) and simulated operational power testing tasks (p < 0.001). Age
      related body composition changes were also observed independent of body mass
      index. Minimum recruitment standards and fitness programs need to account for age
      related declines in physical capabilities to ensure that the minimum standard is
      maintained regardless of age.

PMID- 24588284
TI  - Do not stop publishing case reports.

PMID- 24588285
TI  - Maternal and neonatal morbidity: dual harms associated with addiction in
      pregnancy.

PMID- 24588286
TI  - Association between addiction treatment staff professional and educational levels
      and perceptions of organizational climate and resources.
AB  - BACKGROUND: Research studies have identified addiction treatment staff who have
      higher levels of education as having more positive attitudes about evidence-based
      treatment practices, science-based training, and the usefulness of evidence-based
      practices. This study examined associations between addiction treatment staff
      level of education and their perceptions of 3 measures of organizational change:
      organizational stress, training resources and staffing resources in their
      treatment unit. METHODS: The sample included 588 clinical staff from community
      based substance abuse treatment organizations who received Substance Abuse and
      Mental Health Services Administration (SAMHSA) funding (2003-2008) to implement
      evidence-based practices (EBPs). Bivariate analysis and regression modeling
      methods examined the relationship between staff education level (no high school
      education, high school education, some college, associate's degree, bachelor's
      degree, master's degree, doctoral degree, and other type of degree such as
      medical assistant, registered nurse [RN], or postdoctoral) and attitudes about
      organizational climate (stress), training resources, and staffing resources while
      controlling for staff and treatment unit characteristics. RESULTS: Multivariable
      models identified staff with lower levels of education as having significantly
      more positive attitudes about their unit's organizational capacity. These results
      contradict findings that addiction treatment staff with higher levels of
      education work in units with greater levels of organizational readiness for
      change. CONCLUSION: It cannot be inferred that higher levels of education among
      treatment staff is necessarily associated with high levels of organizational
      readiness for change.

PMID- 24588287
TI  - Pilot test of 12-step linkage for alcohol-abusing women in leaving jail.
AB  - BACKGROUND: More than a million US women are detained in jails each year; many
      have alcohol use disorders (AUDs). AUD intervention with pretrial jail detainees
      presents a logistical challenge due to limited jail stays and lack of resources
      for postrelease treatment. The availability, no-cost entry, and promise of
      anonymity of Alcoholics Anonymous (AA) make it a highly accessible resource for
      underserved populations. However, the outreach of AA volunteers into jails (as
      opposed to prisons) has been limited, and incarcerated women are unlikely to seek
      out strangers for help after release. This study pilot tested an enhanced
      referral approach introducing a 12-step volunteer to a woman in jail who would
      attend a meeting with her after release. METHODS: Participants were 14
      unsentenced female pretrial jail detainees with AUD. Intervention consisted of
      introducing participants detained in jail to female AA volunteers who could
      accompany them to an AA meeting after release. Assessments took place at baseline
      and 1 month after release. This uncontrolled pilot study evaluated the
      feasibility and acceptability of this enhanced referral approach. Pre-post
      alcohol use, drug use, alcohol problems, and AA attendance are also reported.
      RESULTS: Enhanced referral was feasible and acceptable. Many (57%) of the 14
      participants who met with AA volunteers in jail were in contact with those
      volunteers after release from jail. Participants had significantly fewer drinking
      days, heavy drinking days, alcohol problems, and drug-using days during the
      postrelease follow-up than they did before jail detention. CONCLUSIONS: Providing
      linkage between women in jail and female AA volunteers who can accompany them to
      a postrelease meeting is achievable, and may be a disseminable and low-cost
      method to improve alcohol outcomes in this vulnerable population.

PMID- 24588288
TI  - How patients understand the term "nonmedical use" of prescription drugs: insights
      from cognitive interviews.
AB  - BACKGROUND: With rising rates of prescription drug abuse and associated overdose
      deaths, there is great interest in having accurate and efficient screening tools
      that identify nonmedical use of prescription drugs in health care settings. The
      authors sought to gain a better understanding of how patients interpret questions
      about misuse of prescription drugs, with the goal of improving the accuracy and
      acceptability of instruments intended for use in primary care. METHODS: A total
      of 27 English-speaking adult patients were recruited from an urban safety net
      primary care clinic to complete a cognitive interview about a 4-item screening
      questionnaire for tobacco, alcohol, illicit drugs, and misuse of prescription
      drugs. Detailed field notes were analyzed for overall comprehension of the
      screening items on illicit drug use and prescription drug misuse, the accuracy
      with which participants classified drugs into these categories, and whether the
      screening response correctly captured the participant's substance use behavior.
      RESULTS: Based on initial responses to the screening items, 6 (22%) participants
      screened positive for past-year prescription drug misuse, and 8 (30%) for illicit
      drug use. The majority (26/27) of participants correctly interpreted the item on
      illicit drug use, and appropriately classified drugs in this category. Eleven
      (41%) participants had errors in their understanding of the prescription drug
      misuse item. The most common error was classifying use of medications without
      abuse potential as nonmedical use. All cases of misunderstanding the prescription
      drug misuse item occurred among participants who screened negative for illicit
      drug use. CONCLUSIONS: The results suggest that terminology used to describe
      misuse of prescription medications may be misunderstood by many primary care
      patients, particularly those who do not use illicit drugs. Failure to improve
      upon the language used to describe prescription drug misuse in screening
      questionnaires intended for use in medical settings could potentially lead to
      high rates of false-positive results.

PMID- 24588289
TI  - The feasibility of telephone follow-up interviews for monitoring treatment
      outcomes of Australian residential drug and alcohol treatment programs.
AB  - BACKGROUND: Telephone follow-up interviewing is one method of monitoring
      treatment outcomes of individuals involved in drug and alcohol treatment
      programs. The present study is the first to examine the feasibility and
      generalizability of data obtained from telephone follow-up interviews after drug
      and alcohol treatment in Australia. METHODS: Participants attended 1 of 8
      Salvation Army Recovery Service Centres where staff administered outcome measures
      at intake. Three-month postdischarge telephone follow-up interviews were
      conducted by researchers from the Illawarra Institute for Mental Health,
      University of Wollongong. RESULTS: A sample of 700 clients was obtained for
      follow-up (582 males; 118 females). A 51% follow-up rate was achieved at a cost
      of US$82 per completed interview. No significant differences in baseline
      characteristics between responding and nonresponding participants were found.
      CONCLUSIONS: Overall, the telephone methodology was shown to be feasible and
      relatively inexpensive. However, the introduction of outcome measures at the
      service level in parallel with follow-up data collection procedures complicated
      the collection of response data. The burden of introducing outcome measures in
      residential services may be reduced by utilizing a phased implementation
      strategy.

PMID- 24588290
TI  - Training addiction professionals in empirically supported treatments:
      perspectives from the treatment community.
AB  - BACKGROUND: Large-scale dissemination efforts seek to expand opportunities for
      the addiction treatment community to receive training in empirically supported
      treatments (ESTs). Prospective consumers of such training are valuable sources of
      input about content of interest, preferences for how training events are
      structured, and obstacles that deter receipt of training. METHODS: In this mixed
      method study, data were collected in 64 semistructured individual interviews with
      personnel during site visits to 16 community opioid treatment programs (OTPs). At
      each OTP, interviews were completed with the executive director, a clinical
      supervisor, and 2 direct-service clinicians. Topical interests were analyzed
      qualitatively in a cultural domain analysis. Likert ratings of training event
      preferences were analyzed via generalized linear mixed models (GLMMs), and
      unstructured interviewee comments were analyzed via narrative analysis. Obstacles
      to training receipt were analyzed qualitatively with both content coding and
      narrative analysis. RESULTS: Based on topics of reported interest, cultural
      domain analysis suggests as ESTs of note: Multidimensional Family Therapy,
      Motivational Enhancement Therapy, Relapse Prevention Therapy, "Seeking Safety,"
      and broad addiction-focused pharmacotherapy. Regarding training event
      preferences, GLMMs and narrative analysis revealed clear preferences for time
      distributed trainings and use of participatory activities (e.g., trainer
      demonstrations, role plays, small group exercises). Content coding identified
      cost as the primary obstacle to receipt of EST trainings, followed by lack of
      time, logistical challenges, and disinterest, and narrative analysis elaborated
      on contextual issues underlying these obstacles. CONCLUSIONS: As primary
      consumers of EST technologies, the treatment community has valuable input to
      offer. Dissemination efforts may be enhanced by greater consideration of their
      preferences for training content and event structure, as well as practical
      obstacles that challenge their receipt of training.

PMID- 24588291
TI  - Does change in alliance impact alcohol treatment outcomes?
AB  - BACKGROUND: Although both researchers and practitioners widely recognize
      therapeutic alliance's importance in general psychotherapy, studies specific to
      alcohol use treatments have produced mixed results and generally do not
      investigate if and how alliance changes over course of treatment. METHODS: Using
      parallel process latent growth curve modeling, the authors examined if increase
      in alliance was associated with reduced drinking behaviors and a statistical
      mediator in the relationship between treatment modality and outcome. The authors
      used data from Project MATCH (J Stud Alcohol. 1997;58:7-29; Addiction.
      1997;92:1671-1698), which investigated client-treatment matching effects for
      alcohol treatment among outpatient (n = 952) and aftercare (n = 774) participants
      randomized to cognitive behavioral treatment (CBT), 12-step facilitation (TSF),
      or motivational enhancement therapy (MET). RESULTS: Results indicate therapist
      rated alliance increased significantly for CBT and TSF participants, but not MET.
      Participants across modalities in both samples evidenced the largest decrease in
      drinking behaviors from baseline to midtreatment and a slight deterioration in
      treatment gains from midtreatment to 15 months posttreatment. Alliance did not
      mediate the relationship between treatment modality and outcome, but increase in
      alliance was significantly related to decrease in drinking frequency.
      CONCLUSIONS: These findings provide further justification for researchers to
      specifically design studies to examine change in alliance as a mechanism of
      change in alcohol treatments.

PMID- 24588292
TI  - Harm reduction behaviors among young polysubstance users at raves.
AB  - BACKGROUND: Raves may be considered recreational settings in which drug use and
      health risks related to polydrug use are higher than in others. Harm reduction
      behaviors implemented by ravers are of particular relevance in reducing such
      risks. This study analyzes harm reduction behaviors and their relationship to
      raver polysubstance use patterns. METHODS: Cross-sectional study of 248 ravers
      recruited at underground raves in Andalusia (Spain). A questionnaire was
      developed to collect information about their sociodemographics, drug use, and
      harm reduction behaviors. RESULTS: The results show that ravers employ harm
      reduction behaviors for minimizing drug-related harm. Nevertheless, only a small
      minority of the participants frequently employed harm reduction behavior for
      polysubstance use as well. Ravers identified as high polysubstance users
      protected themselves significantly less than those identified as low
      polysubstance users. CONCLUSIONS: This study provides empirical information that
      may be useful for harm reduction intervention in a hidden and hard-to-reach
      population like rave attendees. The results point to the need to inform and
      increase harm reduction behavior specifically aimed at polysubstance use by
      ravers, especially among more frequent users. Future directions for research are
      also suggested.

PMID- 24588293
TI  - The prevalence of positive drug and alcohol screens in elderly trauma patients.
AB  - BACKGROUND: Alcohol and drug abuse are recognized to be significantly prevalent
      in trauma patients, and are frequent harbingers of injury. The incidence of
      substance abuse in elderly trauma patients has, however, been limitedly examined.
      The authors sought to identify the spectrum of positive alcohol and drug
      toxicology screens in patients >=65 years admitted to a Level I trauma center.
      METHODS: Patients >=65 years old admitted to an American College of Surgeons
      (ACS) Level I trauma center over a 60--month period were identified from the
      trauma registry. Demographic data, blood alcohol content (BAC), and urine drug
      screen (UDS) results at admission were obtained and analyzed. The positive
      results were compared with individuals below 65 years in different substance
      categories using Fisher's exact test. RESULTS: In the 5-year period studied, of
      the 4139 patients >=65 years, 1302 (31.5%) underwent toxicological substance
      screening. A positive BAC was present in 11.1% of these patients and a positive
      UDS in 48.3%. The mean BAC level in those tested was 163 mg/dL and 69% of
      patients had a level >80 mg/dL. CONCLUSIONS: These data show that alcohol and
      drug abuse are an issue in patients >=65 years in our institution, though not as
      pervasive a problem as in younger populations. Admission toxicology screens,
      however, are important as an aid to identify geriatric individuals who may
      require intervention.

PMID- 24588294
TI  - The continued care of pregnant women receiving opiate substitution treatment by
      midwives.
AB  - BACKGROUND: The care of pregnant women receiving opiate substitution treatment
      (OST) is generally provided by a variety of health care professionals. Midwives
      working in prenatal consultations take part in this continued care and may meet
      with their patients several times throughout the pregnancy, which can have a
      tremendous impact on monitoring. The purpose of the study was to determine
      whether midwives are used to accompanying women taking OST and to determine their
      level of knowledge and investment in this area. METHODS: One hundred fifty-nine
      midwives working in prenatal consultations in Lille, Roubaix, and Tourcoing
      received a questionnaire with 21 questions. RESULTS: One hundred ten surveys were
      collected and analyzed. The majority (103) of the midwives were attending
      pregnant women taking OST. They were familiar with the effects of heroin on
      pregnancy but were not familiar with the management of OST. CONCLUSIONS: The
      training of these professionals is important in risk reduction, and they should
      know the management of OST. All of the midwives requested specific training.

PMID- 24588295
TI  - Alcohol, tobacco, cocaine, and marijuana use: relative contributions to preterm
      delivery and fetal growth restriction.
AB  - BACKGROUND: Pregnancy substance use is linked to low birth weight. However, less
      is known about relative contributions of various substances and whether effects
      are due to decreased gestational duration, restriction of fetal growth, or both.
      The study goal was to use causal modeling to evaluate the individual impact of
      alcohol, tobacco, cocaine, and marijuana on gestational duration and fetal
      growth. METHODS: Participants were 3164 urban black women recruited at entry to
      prenatal care and followed to delivery, with all gestational dating ultrasound
      supported. Pregnancy substance use was assessed via self-report (alcohol,
      tobacco, cocaine, and marijuana). RESULTS: Alcohol, cigarette, and cocaine use
      were all individually and negatively related to gestational age at delivery.
      However, only alcohol, cigarette, and marijuana use predicted fetal growth, with
      effects for alcohol and cigarette greater and more discrepant for older women.
      Overall, heavy cigarette smoking had the greatest individual impact on birth
      weight (up to 431 g). Heavy levels of use of all 4 substances by older women
      decreased birth weight by 26% (806 g). CONCLUSIONS: For perhaps the first time,
      reduced birth weight is apportioned both by type of substance and mechanism of
      effect. The use of alcohol and/or cigarettes was clearly more harmful to fetal
      growth than cocaine use. Findings demonstrate the need for continued emphasis on
      intervention efforts to address legal and illicit pregnancy substance use.

PMID- 24588296
TI  - Prenatal methamphetamine exposure and neonatal and infant neurobehavioral
      outcome: results from the IDEAL study.
AB  - BACKGROUND: Methamphetamine (MA) use among pregnant women is an increasing
      problem in the United States. How MA use during pregnancy affects neonatal and
      infant neurobehavior is unknown. METHODS: The Infant Development, Environment,
      and Lifestyle (IDEAL) study screened 34,833 subjects at 4 clinical centers. Of
      the subjects, 17,961 were eligible and 3705 were consented, among which 412 were
      enrolled for longitudinal follow-up. Exposed subjects were identified by self
      report and/or gas chromatography/mass spectroscopy (GC/MS) confirmation of
      amphetamine and metabolites in meconium. Comparison subjects were matched (race,
      birth weight, maternal education, insurance), denied amphetamine use, and had a
      negative meconium screen. Both groups included prenatal alcohol, tobacco, and
      marijuana use, but excluded use of opiates, lysergic acid diethylamide, or
      phencyclidine. The Neonatal Intensive Care Unit (NICU) Network Neurobehavioral
      Scale (NNNS) was administered within the first 5 days of life and again at 1
      month to 380 enrollees (185 exposed, 195 comparison). Analysis of variance
      (ANOVA) tested exposure effects on NNNS summary scores at birth and 1 month.
      General linear model (GLM) repeated-measures analysis assessed the effect of MA
      exposure over time on the NNNS scores with and without covariates. RESULTS: By 1
      month of age, both groups demonstrated higher quality of movement (P = .029),
      less lethargy (P = .001), and fewer asymmetric reflexes (P = .012), with no
      significant differences in NNNS scores between the exposed and comparison groups.
      Over the first month of life, arousal increased in exposed infants but decreased
      in comparison infants (P = .031) and total stress was decreased in exposed
      infants, with no change in comparison infants (P = .026). CONCLUSIONS:
      Improvement in total stress and arousal were observed in MA-exposed newborns by 1
      month of age relative to the newborn period.

PMID- 24588297
TI  - I heard about it from a friend: assessing interest in buprenorphine treatment.
AB  - BACKGROUND: In the United States, opioid abuse and dependence continue to be a
      growing problem, whereas treatment for opioid abuse and dependence remains fairly
      static. Buprenorphine treatment for opioid dependence is safe and effective but
      underutilized. Prior research has demonstrated low awareness and use of
      buprenorphine among marginalized groups. This study investigates syringe exchange
      participants' awareness of, exposure to, and interest in buprenorphine treatment.
      METHODS: Syringe exchange participants were recruited from a mobile unit
      performing outreach to 9 street-side sites in New York City. Computer-based
      interviews were conducted to determine (1) opioid users' awareness of, exposure
      to, and interest in buprenorphine treatment; and (2) the association between
      awareness or exposure and interest in buprenorphine treatment. Logistic
      regression models were used to examine the associations between awareness of,
      direct exposure (i.e., having taken buprenorphine) or indirect exposure (i.e.,
      knowing someone who had taken buprenorphine)S to, and interest in buprenorphine
      treatment. RESULTS: Of 158 opioid users, 70% were aware of, 32% had direct
      exposure to, and 31% had indirect exposure to buprenorphine; 12% had been
      prescribed buprenorphine. Of 138 opioid users who had never been prescribed
      buprenorphine, 57% were interested in buprenorphine treatment. In multivariate
      models, indirect exposure was associated with interest in buprenorphine treatment
      (adjusted odds ratio [AOR] = 2.65, 95% confidence interval [CI]: 1.22-5.77), but
      awareness and direct exposure were not. CONCLUSIONS: Syringe exchange
      participants were mostly aware of buprenorphine and interested in treatment, but
      few had actually been prescribed buprenorphine. Because indirect exposure to
      buprenorphine was associated with interest in treatment, future interventions
      could capitalize on indirect exposure, such as through peer mentorship, to
      address underutilization of buprenorphine treatment.

PMID- 24588299
TI  - Cytomorphometric analysis of oral buccal mucosal smears in tobacco and arecanut
      chewers who abused with and without betel leaf.
AB  - BACKGROUND: Tobacco in any form (smoking or chewing), arecanut chewing, and
      alcohol are considered to be the major extrinsic etiological factors for
      potentially malignant disorders of the oral cavity and for squamous cell
      carcinoma, the most common oral malignancy in India. An increase in nuclear
      diameter (ND) and nucleus-cell ratio (NCR) with a reduction in cell diameter (CD)
      are early cytological indicators of dysplastic change. The authors sought to
      identify cytomorphometric changes in ND, CD, and NCR of oral buccal cells in
      tobacco and arecanut chewers who chewed with or without betel leaf. METHODS:
      Participants represented 3 groups. Group I consisted of 30 individuals who chewed
      tobacco and arecanut with betel leaf (BQT chewers). Group II consisted of 30
      individuals who chewed tobacco and arecanut without betel leaf (Gutka chewers).
      Group III comprised 30 apparently healthy nonabusers. Cytological smears were
      prepared and stained with modified-Papanicolaou stain. RESULTS: Comparisons
      between Groups I and II and Groups II and III showed that ND was increased, with
      P values of .054 and .008, respectively, whereas a comparison of Groups I and III
      showed no statistical significance. Comparisons between Groups I and II and
      Groups II and III showed that CD was statistically reduced, with P values of .037
      and <.000, respectively, whereas comparison of Groups I and III showed no
      statistical significance. Comparisons between Groups I and II and groups II and
      III showed that NCR was statistically increased, with P values of <.000, whereas
      a comparison of Groups I and III showed no statistical significance. CONCLUSIONS:
      CD, ND, and NCR showed statistically significant changes in Group II in
      comparison with Group I, which could indicate larger and earlier risk of
      carcinoma for Gutka chewers than in BQT chewers.

PMID- 24588298
TI  - Expressive writing as a therapeutic process for drug-dependent women.
AB  - BACKGROUND: Although women with substance use disorders (SUDs) have high rates of
      trauma and posttraumatic stress, many addiction programs do not offer trauma
      specific treatments. One promising intervention is Pennebaker's expressive
      writing, which involves daily, 20-minute writing sessions to facilitate
      disclosure of stressful experiences. METHODS: Women (N = 149) in residential
      treatment completed a randomized clinical trial comparing expressive writing with
      control writing. Repeated-measures analysis of variance was used to document
      change in psychological and physical distress from baseline to 2-week and 1-month
      follow-ups. Analyses also examined immediate levels of negative affect following
      expressive writing. RESULTS: Expressive writing participants showed greater
      reductions in posttraumatic symptom severity, depression, and anxiety scores,
      when compared with control writing participants at the 2-week follow-up. No group
      differences were found at the 1-month follow-up. Safety data were encouraging:
      although expressive writing participants showed increased negative affect
      immediately after each writing session, there were no differences in pre-writing
      negative affect scores between conditions the following day. By the final writing
      session, participants were able to write about traumatic/stressful events without
      having a spike in negative affect. CONCLUSIONS: Results suggest that expressive
      writing may be a brief, safe, low-cost, adjunct to SUD treatment that warrants
      further study as a strategy for addressing posttraumatic distress in substance
      abusing women.

PMID- 24588300
TI  - Frequency of energy drink use predicts illicit prescription stimulant use.
AB  - BACKGROUND: The purpose of this study was to examine energy drink (ED) usage
      patterns and to investigate the illicit use of prescription stimulants among
      college students. METHODS: A sample of 267 undergraduate and graduate students
      (mean age of 22.48 among stimulant users) from a large midwestern university and
      its branch campus locations voluntarily participated in the study. RESULTS: Among
      prescription stimulant users without a valid medical prescription, Mann-Whitney U
      tests and logistic regression analysis revealed that the frequency of ED use was
      a significant predictor of the illicit use of prescription stimulants. Moreover,
      frequency of ED consumption was a significant predictor of the illicit use of
      prescription stimulant medications, with the odds for using increasing by .06
      with each additional day of ED use past 0 day (odds for use = 1.06, P =.008).
      CONCLUSIONS: Results indicate that the frequency of ED use is a significant
      predictor of the illicit use of prescription stimulants. All prescription
      stimulant users with or without a valid script also used EDs. This finding is
      important to practitioners because of the harmful interactions (eg, serotonin
      syndrome) that can occur when ED ingredients (eg, ginseng, yohimbine, evodamine,
      etc) are mixed with prescription stimulants.

PMID- 24588301
TI  - Relationship between COPD and lower socioeconomic status in farmers from South
      Eastern Poland (Lublin region).
AB  - INTRODUCTION: Lower socioeconomic status is considered to be an independent risk
      factor of chronic conditions, such as chronic obstructive pulmonary disease
      (COPD). COPD, one of the major public health problems worldwide, is a chronic
      inflammatory lung disease of a multifactorial background. COPD morbidity in rural
      areas has been higher than in urban settings, as apart from the major causative
      factor, tobacco smoking, the burden of this disease in rural environments is also
      connected to additional occupational factors (organic dusts). The management of
      chronic diseases seems to be particularly difficult in rural areas. The aim of
      the study was to analyze the socioeconomic status of farmers suffering from COPD
      in comparison to healthy farmers. METHODS: Thirty farmers with COPD and 34
      healthy farmers from the Lublin region (Poland) were investigated based on the
      area of land they possessed (an indicator used in the health insurance system in
      Poland to classify farmers). The farmers from five rural communes were selected
      by general practitioners. Statistical analysis was performed by non-parametric
      Mann-Whitney U-test for the differences between area of farms. The p < 0.05 level
      was considered as significant. RESULTS: Area of land (median: 1.5 ha, 25th-75th
      percentile: 1.0-4.0) owned by farmers with COPD was significantly lower than area
      of farms belonging to healthy farmers (median: 7.0 ha, 25th-75th percentile: 3.0
      10.0) (p < 0001, Mann-Whitney U-test). CONCLUSIONS: In rural areas individuals
      with COPD are characterized by significantly lower socioeconomic status than
      healthy persons. COPD is a major health problem, especially in rural areas, which
      may indicate that policy-makers should consider addressing equity in COPD
      management in rural areas.

PMID- 24588302
TI  - Podoplanin expression in cancer-associated fibroblasts predicts aggressive
      behavior in melanoma.
AB  - BACKGROUND: Recent studies have showed podoplanin expression in several tumors,
      which has been associated with lymph node metastasis and poor prognosis.
      Podoplanin expression in cancer-associated fibroblasts also correlates with tumor
      progression. However, the association of podoplanin expression with melanomas
      remains unclear. METHODS: To clarify the prognostic significance of podoplanin in
      melanoma, podoplanin expression in tumor cells and cancer-associated fibroblasts
      was examined by immunohistochemistry in tissue samples collected from 55 melanoma
      patients. RESULTS: Podoplanin expression in tumor cells was identified in 38
      patients (69.1%) but did not show correlation with characteristics of tumor
      progression such as tumor thickness (p = 0.52) and sentinel lymph node (SLN)
      metastasis (p = 0.79). Podoplanin expression in cancer-associated fibroblasts was
      observed in 25 patients (45.5%), 11 of whom (44.0%) had SLN metastasis. In
      contrast, only 4 of 30 patients (13.3%) with podoplanin-negative cancer
      associated fibroblasts exhibited SLN metastasis. Podoplanin-positive cancer
      associated fibroblasts were associated with increased tumor thickness and SLN
      metastasis. Furthermore, patients with podoplanin-positive cancer-associated
      fibroblasts had poorer survival than those with podoplanin-negative cancer
      associated fibroblasts (p = 0.0148). CONCLUSION: The presence of podoplanin
      expression in cancer-associated fibroblasts correlates with aggressive behavior
      in melanoma and might therefore serve as a useful prognostic factor for patients
      with melanoma.

PMID- 24588303
TI  - Isolation and biosynthesis of preussin B, a pyrrolidine alkaloid from
      Simplicillium lanosoniveum.
AB  - A new pyrrolidine alkaloid, preussin B (1), was isolated from the culture extract
      of the fungus Simplicillium lanosoniveum TAMA 173 along with the known congener
      preussin (2). The structure and absolute configuration of 1 were determined by
      spectroscopic analysis and spectral comparison with 2. Feeding experiments with
      13C-labeled precursors revealed that the pyrrolidine ring of 1 was assembled from
      acetate and l-phenylalanine by a PKS-NRPS hybrid biosynthetic pathway.

PMID- 24588304
TI  - Do anti-angiogenic cancer therapies increase risk of significant weight loss?
AB  - INTRODUCTION: Angiogenesis is important in many disease states such as cancer.
      Anti-angiogenic cancer drugs are in broad use for the treatment of cancers.
      However, currently most of these anticancer drugs result in some adverse effects
      in the patient. AREAS COVERED: In this paper, we review evidence on the
      association between anti-angiogenic therapies and weight loss. We report on basic
      experiments and clinical trials that measure weight loss with anti-angiogenic
      cancer therapies. EXPERT OPINION: Few strong associations are found between anti
      angiogenic cancer therapies and weight loss, with the exception of some
      multikinase inhibitors in clinical trials. Anti-angiogenic cancer therapies
      appear safe in relation to weight loss, but the result needs to be established by
      further clinical trials.

PMID- 24588305
TI  - Oxidation rate of magnesium sulfite catalyzed by cobalt ions.
AB  - Oxidation of magnesium sulfite is important for recycle of byproduct in the
      magnesium desulfurization. The oxidation rate of magnesium sulfite, prepared by
      vacuum evaporation method, was investigated in a bubbling tank in presence of
      transition metal catalysts, which shows cobalt is the most effective. The general
      reaction orders with respect to cobalt, magnesium sulfite, and oxygen are 0.44,
      0, and 0.46, respectively, and the apparent activity energy is 17.43 KJ.mol. The
      catalytic performance of cobalt compared with other metals was also analyzed
      employing the ion potential theory. Integrated with the three-phase reaction
      model, we inferred that the general oxidation rate of magnesium sulfite is
      controlled by mass transfer of oxygen. Further, the intrinsic kinetics was
      predicted, indicating that the reaction orders with respect to cobalt and oxygen
      are 1.0 and 0, respectively. The results are helpful for the recycle of magnesium
      sulfite in magnesia desulfurization. 

PMID- 24588306
TI  - A novel technique of detecting MRI-negative lesion in focal symptomatic epilepsy:
      intraoperative ShearWave elastography.
AB  - Focal symptomatic epilepsy is the most common form of epilepsy that can often be
      cured with surgery. A small proportion of patients with focal symptomatic
      epilepsy do not have identifiable lesions on magnetic resonance imaging (MRI).
      The most common pathology in this group is type II focal cortical dysplasia
      (FCD), which is a subtype of malformative brain lesion associated with medication
      resistant epilepsy. We present a patient with MRI-negative focal symptomatic
      epilepsy who underwent invasive electrode recordings. At the time of surgery, a
      novel ultrasound-based technique called ShearWave Elastography (SWE) was
      performed. A 0.5 cc lesion was demonstrated on SWE but was absent on B-mode
      ultrasound and 3-T MRI. Electroencephalography (EEG), positron emission
      tomography (PET), and magnetoencephalography (MEG) scans demonstrated an
      abnormality in the right frontal region. On the basis of this finding, a depth
      electrode was implanted into the lesion. Surgical resection and histology
      confirmed the lesion to be type IIb FCD. A PowerPoint slide summarizing this
      article is available for download in the Supporting Information section here. 

PMID- 24588307
TI  - Water adsorption in porous metal-organic frameworks and related materials.
AB  - Water adsorption in porous materials is important for many applications such as
      dehumidification, thermal batteries, and delivery of drinking water in remote
      areas. In this study, we have identified three criteria for achieving high
      performing porous materials for water adsorption. These criteria deal with
      condensation pressure of water in the pores, uptake capacity, and recyclability
      and water stability of the material. In search of an excellently performing
      porous material, we have studied and compared the water adsorption properties of
      23 materials, 20 of which are metal-organic frameworks (MOFs). Among the MOFs are
      10 zirconium(IV) MOFs with a subset of these, MOF-801-SC (single crystal form), 
      802, -805, -806, -808, -812, and -841 reported for the first time. MOF-801-P
      (microcrystalline powder form) was reported earlier and studied here for its
      water adsorption properties. MOF-812 was only made and structurally characterized
      but not examined for water adsorption because it is a byproduct of MOF-841
      synthesis. All the new zirconium MOFs are made from the Zr6O4(OH)4(-CO2)n
      secondary building units (n = 6, 8, 10, or 12) and variously shaped carboxyl
      organic linkers to make extended porous frameworks. The permanent porosity of all
      23 materials was confirmed and their water adsorption measured to reveal that MOF
      801-P and MOF-841 are the highest performers based on the three criteria stated
      above; they are water stable, do not lose capacity after five
      adsorption/desorption cycles, and are easily regenerated at room temperature. An
      X-ray single-crystal study and a powder neutron diffraction study reveal the
      position of the water adsorption sites in MOF-801 and highlight the importance of
      the intermolecular interaction between adsorbed water molecules within the pores.

PMID- 24588308
TI  - Toward vibrational dynamics at liquid-liquid and nano-interfaces: time-resolved
      sum-frequency scattering.
AB  - Interfacial molecular dynamics are key to understanding many phenomena in
      technology and life sciences. We demonstrate a first step toward accessing
      vibrational dynamics at liquid-liquid and nanoscopic (bio)-interfaces using time
      resolved sum-frequency scattering to probe the interfaces of a nanodroplet
      platform. The free induction decay of the vibrational modes of dodecylsulfate
      amphiphiles from the interface of dispersed nanoscopic oil droplets was measured.
      We probed the vibrational response of both the functional headgroup and the alkyl
      tail of the amphiphiles. In the molecular fingerprint region, a beating of
      vibrational modes was observed. Simultaneous modeling of the time- and frequency
      resolved response revealed modes at ~995 and ~1065 cm(-1) that can be assigned to
      C-O-S and SO3 stretch vibrations. 

PMID- 24588309
TI  - Is amalgam ready to be buried?

PMID- 24588310
TI  - Current perspectives on the role of ridge (socket) preservation procedures in
      dental implant treatment in the aesthetic zone.
AB  - Augmentation of the extraction socket (ridge preservation) is increasingly being
      advocated in anticipation of implant placement. The aim of this article is to
      review the available evidence with regards to ridge preservation procedures,
      investigating whether these techniques improve dental implant treatment outcomes.
      Evidence is examined to compare these techniques to other treatment alternatives
      such as implant placement with simultaneous lateral augmentation. An electronic
      PubMed search was conducted using search terms relevant to assessing treatment
      outcomes in association with ridge preservation. Titles were screened and full
      text obtained where relevant. Further full text articles were obtained from
      analysis of those papers yielded from the original search. Twenty-two papers were
      finally selected for analysis. Ridge preservation techniques are effective in
      minimizing post-extraction alveolar ridge contraction. However, there is
      insufficient evidence to suggest that the use of these techniques in conjunction
      with dental implant treatment improves implant treatment outcomes. Furthermore,
      ridge preservation does not necessarily eliminate the need for further
      simultaneous augmentation at the time of implant placement. The delayed healing
      associated with ridge preservation using socket grafting necessitates a
      commitment to a delayed placement protocol. The extended treatment time,
      compromised healing and expense related to ridge preservation suggests a more
      cautious approach with regards to the indication of such techniques. 

PMID- 24588311
TI  - Simultaneous adenomatoid odontogenic and keratocystic odontogenic tumours in a
      patient with Gorlin-Goltz syndrome.
AB  - Gorlin and Goltz described a syndrome in which multiple basal cell carcinomas,
      odontogenic keratocysts and bifid ribs occurred in combination. The jaw
      keratocysts are a consistent feature of 'Gorlin-Goltz' or naevoid basal cell
      carcinoma syndrome. Central nervous system and ocular involvement occurred
      together with the fairly typical facial features of frontal bossing and
      hypertelorism. This case report documents the pathology associated with an
      impacted maxillary canine tooth in a boy with Gorlin-Goltz syndrome. The patient
      presented for investigation of the failure of eruption of the right permanent
      maxillary canine tooth. Radiographic investigation showed the presence of a well
      circumscribed radiolucency located around the crown of an impacted right
      maxillary canine tooth. The patient's medical history revealed a medulloblastoma
      that was treated 13 years ago. The right maxillary canine tooth and associated
      peri-coronal tissue were removed under general anaesthetic. A diagnosis of a
      keratocystic odontogenic tumour with an associated adenomatoid odontogenic tumour
      was made. The common differential diagnoses for a peri-coronal radiolucency in
      the maxilla that need to be considered by dentists include a dentigerous cyst,
      follicular keratocystic odontogenic tumour and adenomatoid odontogenic tumour. A
      rare case of both keratocystic odontogenic tumour and associated follicular
      adenomatoid odontogenic tumour is described in a patient with naevoid basal cell
      carcinoma syndrome.

PMID- 24588314
TI  - Short-term effects of intravitreal bevacizumab on cornea and anterior chamber.
AB  - PURPOSE: To determine the short-term effects of single-dose intravitreal
      bevacizumab injection on central corneal thickness (CCT), simulated keratometry
      (Sim K), anterior chamber depth (ACD), iridocorneal angle (ICA) and intraocular
      pressure (IOP) measurements. DESIGN: Prospective, nonrandomized, interventional
      clinical trial. MATERIALS AND METHODS: Forty-three eyes of 43 patients aged
      between 41 and 78 years (average 62 +/- 13 years) received an intravitreal
      injection of 2.5 mg/0.1 mL bevacizumab. Patients who had not undergone additional
      intravitreal anti-vascular endothelial growth factor therapy within 6 months were
      included in the study. CCT, Sim K, ACD and ICA measurements were obtained with
      Sirius Topographer. IOP measurements were taken after topographic measurements
      with Goldmann applanation tonometer. The CCT, ACD, ICA and IOP measurements were
      taken before and after 3rd, 15th days and 1st month of intravitreal bevacizumab
      injection. RESULTS: Pre- and postinjection of 3rd, 15th days and 1st month CCT (p
      = 0.999), Sim K (p = 0.746), ACD (p = 0.996), ICA (p = 0.632) and IOP (p = 0.707)
      measurements were not statistically different. Mean CCT (p = 1.000), Sim K
      (0.972), ACD (p = 0.998), ICA (0.667) and IOP (0.951) values were similar before
      and after 3rd day of bevacizumab injection. Mean CCT (p = 0.999), Sim K (p =
      0.994), ACD (p = 1.000), ICA (p = 0.999) and IOP (p = 1.000) measurements were
      also similar before and after 15th day of injection. Preinjection and 1st month
      of postinjection CCT (p = 0.999), Sim K (p = 0.932), ACD (p = 0.998), ICA (p =
      1.000) and IOP (p = 0.741) measurements did not change significantly.
      CONCLUSIONS: Single-dose intravitreal bevacizumab injection does not affect CCT,
      Sim K, ACD, ICA and IOP in short-term period.

PMID- 24588315
TI  - Psychologists in medical schools and academic medical centers: over 100 years of
      growth, influence, and partnership.
AB  - Psychologists have served on the faculties of medical schools for over 100 years.
      Psychologists serve in a number of different roles and make substantive
      contributions to medical schools' tripartite mission of research, education, and
      clinical service. This article provides an overview of the history of
      psychologists' involvement in medical schools, including their growing presence
      in and integration with diverse departments over time. We also report findings
      from a survey of medical school psychologists that explored their efforts in
      nonclinical areas (i.e., research, education, administration) as well as clinical
      endeavors (i.e., assessment, psychotherapy, consultation). As understanding of
      the linkage between behavioral and psychological factors and health status and
      treatment outcomes increases, the roles of psychologists in health care are
      likely to expand beyond mental health. An increasing focus on accountability
      related to treatment outcomes and interprofessional research, education, and
      models of care delivery-will likely provide additional opportunities for
      psychologists within health care and professional education. The well-established
      alignment of psychologists' expertise and skills with the mission and complex
      organizational needs of medical schools augurs a partnership on course to grow
      stronger. (PsycINFO Database Record (c) 2014 APA, all rights reserved). 

PMID- 24588316
TI  - Traumatic brain injury among Indiana state prisoners.
AB  - Research on traumatic brain injury among inmates has focused on comparing the
      rate of traumatic brain injury among offenders to the general population, but
      also how best to screen for traumatic brain injury among this population. This
      study administered the short version of the Ohio State University Traumatic Brain
      Injury Identification Method to all male inmates admitted into Indiana state
      prisons were screened for a month (N = 831). Results indicate that 35.7% of the
      inmates reported experiencing a traumatic brain injury during their lifetime and
      that these inmates were more likely to have a psychiatric disorder and a prior
      period of incarceration than those without. Logistic regression analysis finds
      that a traumatic brain injury predicts the likelihood of prior incarceration net
      of age, race, education, and psychiatric disorder. This study suggests that brief
      instruments can be successfully implemented into prison screenings to help divert
      inmates into needed treatment. 

PMID- 24588317
TI  - Learn to lead in the boardroom.
AB  - Nurses, positioned as members of one of the most highly trusted professions, are
      called to meet the health needs of patients and communities in a variety of ways.
      The Institute of Medicine calls nurses to partner with physicians and other
      professionals to redesign health care in the United States. One way that nurses
      can answer the call is by serving in the boardroom, where decisions regarding
      health and health care are made. Identified competencies for board leadership
      include (a) open communication, (b) planning, (c) active engagement, (d)
      collaboration, (e) decision-making skills, (f) financial stewardship, (g)
      organizational skills, (h) advocacy, and (i) visionary skills. Board competency
      development begins in nursing school and continues throughout one's professional
      career. A board leadership self-assessment tool is provided as a guide for
      personal and professional growth. Continuing education professionals play an
      important role in development of boardroom competency.

PMID- 24588318
TI  - Extended defects formation in nanosecond laser-annealed ion implanted silicon.
AB  - Damage evolution and dopant distribution during nanosecond laser thermal
      annealing of ion implanted silicon have been investigated by means of
      transmission electron microscopy, secondary ion mass spectrometry, and atom probe
      tomography. Different melting front positions were realized and studied: nonmelt,
      partial melt, and full melt with respect to the as-implanted dopant profile. In
      both boron and silicon implanted silicon samples, the most stable form among the
      observed defects is that of dislocation loops lying close to (001) and with
      Burgers vector parallel to the [001] direction, instead of conventional {111}
      dislocation loops or {311} rod-like defects, which are known to be more
      energetically favorable and are typically observed in ion implanted silicon. The
      observed results are explained in terms of a possible modification of the defect
      formation energy induced by the compressive stress developed in the nonmelted
      regions during laser annealing. 

PMID- 24588319
TI  - New and recurrent AAGAB mutations in punctate palmoplantar keratoderma.

PMID- 24588320
TI  - Engineering DNA self-assemblies as templates for functional nanostructures.
AB  - CONSPECTUS: DNA is a well-known natural molecule that carries genetic
      information. In recent decades, DNA has been used beyond its genetic role as a
      building block for the construction of engineering materials. Many strategies,
      such as tile assembly, scaffolded origami and DNA bricks, have been developed to
      design and produce 1D, 2D, and 3D architectures with sophisticated morphologies.
      Moreover, the spatial addressability of DNA nanostructures and sequence-dependent
      recognition enable functional elements to be precisely positioned and allow for
      the control of chemical and biochemical processes. The spatial arrangement of
      heterogeneous components using DNA nanostructures as the templates will aid in
      the fabrication of functional materials that are difficult to produce using other
      methods and can address scientific and technical challenges in interdisciplinary
      research. For example, plasmonic nanoparticles can be assembled into well-defined
      configurations with high resolution limit while exhibiting desirable collective
      behaviors, such as near-field enhancement. Conducting metallic or polymer
      patterns can be synthesized site-specifically on DNA nanostructures to form
      various controllable geometries, which could be used for electronic nanodevices.
      Biomolecules can be arranged into organized networks to perform programmable
      biological functionalities, such as distance-dependent enzyme-cascade activities.
      DNA nanostructures can carry multiple cytoactive molecules and cell-targeting
      groups simultaneously to address medical issues such as targeted therapy and
      combined administration. In this Account, we describe recent advances in the
      functionalization of DNA nanostructures in different fashions based on our
      research efforts in nanophotonics, nanoelectronics, and nanomedicine. We show
      that DNA origami nanostructures can guide the assembly of achiral, spherical,
      metallic nanoparticles into nature-mimicking chiral geometries through
      hybridization between complementary DNA strands on the surface of nanoparticles
      and DNA scaffolds, to generate circular dichroism (CD) response in the visible
      light region. We also show that DNA nanostructures, on which a HRP-mimicking
      DNAzyme acts as the catalyst, can direct the site-selective growth of conductive
      polymer nanomaterials with template configuration-dependent doping behaviors. We
      demonstrate that DNA origami nanostructures can act as an anticancer-drug
      carrier, loading drug through intercalation, and can effectively circumvent the
      drug resistance of cultured cancer cells. Finally, we show a label-free strategy
      for probing the location and stability of DNA origami nanocarriers in cellular
      environments by docking turn-off fluorescence dyes in DNA double helices. These
      functionalizations require further improvement and expansion for realistic
      applications. We discuss the future opportunities and challenges of DNA based
      assemblies. We expect that DNA nanostructures as engineering materials will
      stimulate the development of multidisciplinary and interdisciplinary research.

PMID- 24588321
TI  - Antioxidant and antiangiogenic activity of Astronium graveolens Jacq. leaves.
AB  - Angiogenesis is involved in many physiological and pathological conditions.
      Natural compounds with antioxidant activity have also been reported to possess
      potent antiangiogenic properties by regulating angiogenesis modulators such as
      vascular endothelial growth factor (VEGF). Based on this, we screened the
      antioxidant and antiangiogenic activities of Astronium graveolens leaf extracts
      by a DPPH test and a competitive enzyme-linked immunosorbent assay, respectively.
      MeOH extract expressed a significant free radical-scavenging activity (EC50 =
      37.65 MUg/mL) and it was able to inhibit the interaction between placental growth
      factor (PlGF) (placental growth factor), a VEGF family member, and its receptor
      Flt-1 by more than 50% at 1 mg/mL. 1,2,3,4,6-Penta-O-galloyl-d-glucopyranose, 6
      is the most active compound of the extract. It exhibited a high potency in
      scavenging DPPH (EC50 = 2.16 MUg/mL) and reduced by 58% the PlGF/Flt-1
      interaction at a concentration of 50 MUM. Moreover, the known compounds (1-6)
      have been isolated for the first time in A. graveolens.

PMID- 24588322
TI  - Nitric oxide and antioxidant enzyme levels in blood of respiratory distress
      syndrome--Egyptian preterms and their mothers.
AB  - BACKGROUND: The mechanisms of tissue injury in respiratory distress syndrome
      (RDS) have not been completely elucidated but the involvement of oxidative damage
      due to reactive oxygen species (ROS) is important in the pathogenesis of preterm
      labor and RDS. OBJECTIVES: To assess the oxidative status in preterms with and
      without RDS and in their mothers. PATIENTS AND METHODS: Measuring and comparing
      concentrations of serum nitric oxide (NO), and erythrocytic activities of some
      antioxidant enzymes in blood of 20 preterms with RDS and 20 preterms without and
      their mothers, respectively. RESULTS: Our results confirm significant elevation
      of mean levels of serum NO and reduced mean levels of erythrocytic activities of
      antioxidant enzymes, superoxide dismutase (SOD), glutathione peroxidase (GPx) and
      catalase (CAT), in RDS preterms and their mothers compared with controls and
      their mothers. A significant positive correlations were found between maternal
      and preterm serum NO (r=0.3 & 0.6) and erythrocytic activity of SOD (r=0.5 & 0.4)
      for RDS and control groups, respectively. In addition, a significant negative
      correlations were found between NO and SOD in all groups. CONCLUSIONS: The
      existence of oxygen metabolites and lipid peroxidation was significantly more
      obvious in RDS preterms and in their mothers than those without.

PMID- 24588323
TI  - The incidence and risk factors for developing depression after being diagnosed
      with inflammatory bowel disease: a cohort study.
AB  - BACKGROUND: Studies have found that depression is more frequent in patients with
      inflammatory bowel disease (IBD) than the general population. Clinicians are now
      trying to pinpoint risk factors for psychological impairment in the IBD
      population. AIMS: To examine the demographic and phenotypic variables associated
      with the development of depression among a diverse cohort of IBD patients. We
      also sought to describe psychotropic therapy prescribed to IBD patients. METHODS:
      We conducted a retrospective cohort study including patients with Crohn's disease
      (CD) and ulcerative colitis (UC) without a prior psychiatric diagnosis and
      followed in the gastroenterology clinics of the private university hospital and
      public safety net hospital at a large academic centre in Miami (Florida).
      Predictive variables included demographic characteristics, IBD phenotype,
      exposure to IBD medications, history of a surgical stoma or seton placement,
      extra-intestinal manifestations, laboratory indices, aggressive disease and
      disease activity (based on imaging and endoscopic parameters). Proportional
      hazard regression models and stepwise Cox regression analysis were used for
      statistical analysis. RESULTS: Independent predictors of depression were female
      gender [HR: 1.3 (95% CI: 1.1-1.7), P = 0.01], aggressive disease [HR: 1.4 (95%
      CI: 1.02-1.9), P = 0.03] and active disease [HR: 1.5 (95% CI: 1.1-2.0), P =
      0.04]. In the group that did develop a depressive disorder, 65% received
      pharmacologic therapy with one or more psychotropic agents. CONCLUSIONS: We found
      female gender, aggressive disease and increased endoscopic/radiological activity
      to be independently associated with the development of depression in inflammatory
      bowel disease.

PMID- 24588324
TI  - TERT promoter mutation is uncommon in acral lentiginous melanoma.
AB  - BACKGROUND: Melanoma is a heterogeneous group of diseases with distinct sets of
      genetic changes. Recurrent and mutually exclusive C>T or CC>TT transition
      mutations were identified in the promoter region of the reverse transcriptase
      catalytic subunit of the telomerase gene (TERT) in melanoma recently, and it was
      suggested that they enhanced the expression of TERT gene and played important
      roles in the melanoma pathogenesis. These mono or di-nucleotide transitions were
      ultraviolet (UV)-signature mutations. METHODS: In this study, polymerase chain
      reaction and direct sequencing of TERT promoter using formalin-fixed and paraffin
      embedded tissue was performed to investigate whether these UV-signature mutations
      were also present in acral lentiginous melanoma. RESULTS: TERT promoter mutation
      was identified in only 2 of the 32 cases (6%) of acral lentiginous melanomas
      while it was identified in 3 of the 9 cases (33%) of non-acral cutaneous
      melanomas. The difference was statistically significant (p = 0.028). CONCLUSIONS:
      The rarity of TERT promoter mutation in the acral lentiginous melanoma was
      consistent with the supposed role of UV light in the melanoma pathogenesis and
      also corroborated the view that acral lentiginous melanomas have a different
      pathogenesis with the melanomas from sun-exposed sites.

PMID- 24588325
TI  - Dopamine-assisted deposition of dextran for nonfouling applications.
AB  - Nonfouling surfaces are essential for many biomedical applications, such as
      diagnostic biosensors and blood- or tissue-contacting implants. In this study, we
      demonstrate a simple one-step method to introduce dextran onto various substrates
      based on dopamine polymerization. It has been shown for the first time that
      dextran molecules could be incorporated into a dopamine polymerization product
      via mixing dextran with dopamine in a slightly alkaline solution. The codeposited
      film was characterized by X-ray photoelectron spectroscopy (XPS), the water
      contact angle, ellipsometry, and atomic force microscopy (AFM). Results reveal
      that it is possible to control the thickness and surface roughness via the
      deposition time and deposition repeat cycles. Furthermore, quartz crystal
      microbalance (QCM) measurements show that the dextran-modified surface inhibits
      protein adhesion. In addition, cell attachment has been significantly inhibited
      on dextran-modified surfaces even after exposure to water for as long as 2
      months. The described dopamine-assisted dextran modification represents a simple
      and universal method for nonfouling surface preparation and can be potentially
      applied to improve the performance of various medical devices and materials. 

PMID- 24588327
TI  - Involvement of myeloperoxidase and NADPH oxidase in the covalent binding of
      amodiaquine and clozapine to neutrophils: implications for drug-induced
      agranulocytosis.
AB  - Amodiaquine (AQ) and clozapine (CLZ) are associated with a relatively high
      incidence of idiosyncratic agranulocytosis, a reaction that is suspected to
      involve covalent binding of reactive metabolites to neutrophils. Previous studies
      have shown that both AQ and CLZ are oxidized to reactive intermediates in vitro
      by activated neutrophils or by the combination of hydrogen peroxide and
      myeloperoxidase (MPO). Neutrophil activation leads to an oxidative burst with
      activation of NADPH oxidase and the production of hydrogen peroxide. However, the
      importance of this pathway in covalent binding in vivo has not been examined. In
      this study, we found that the binding of both AQ and CLZ to neutrophils from MPO
      knockout mice ex vivo decreased approximately 2-fold compared to neutrophils from
      wild-type mice, whereas binding to activated neutrophils from gp91 knockout
      (NADPH oxidase null) mice decreased 6-7-fold. When the AQ studies were performed
      in vivo, again the binding was decreased in MPO knockout mice to about 50% of the
      binding in wild-type mice; however, covalent binding was significant in the
      absence of MPO. Surprisingly, there was no significant decrease in covalent
      binding of AQ to neutrophils in vivo in gp91 knockout mice. In addition, there
      was extensive binding of AQ to many types of bone marrow cells and to peripheral
      lymphocytes. These results indicate that MPO is not the only neutrophil enzyme
      involved in the oxidation of AQ and that NADPH oxidase is not the major source of
      peroxide. There was also no decrease in AQ binding to neutrophils in COX-1 or COX
      2 knockout mice. We were not able to readily reproduce the AQ in vivo studies
      with CLZ because of its acute toxicity in mice. These are the first studies to
      examine the enzymes involved in the bioactivation of AQ by neutrophils in vivo.

PMID- 24588326
TI  - Episodic heavy drinking and 20-year total mortality among late-life moderate
      drinkers.
AB  - BACKGROUND: Analyses of moderate drinking have focused overwhelmingly on average
      consumption, which masks diverse underlying drinking patterns. This study
      examined the association between episodic heavy drinking and total mortality
      among moderate-drinking older adults. METHODS: At baseline, the sample was
      comprised of 446 adults aged 55 to 65; 74 moderate drinkers who engaged in
      episodic heavy drinking and 372 regular moderate drinkers. The database at
      baseline also included a broad set of sociodemographic, behavioral, and health
      status covariates. Death across a 20-year follow-up period was confirmed
      primarily by death certificate. RESULTS: In multiple logistic regression
      analyses, after adjusting for all covariates, as well as overall alcohol
      consumption, moderate drinkers who engaged in episodic heavy drinking had more
      than 2 times higher odds of 20-year mortality in comparison with regular moderate
      drinkers. CONCLUSIONS: Among older moderate drinkers, those who engage in
      episodic heavy drinking show significantly increased total mortality risk
      compared to regular moderate drinkers. Episodic heavy drinking-even when average
      consumption remains moderate-is a significant public health concern.

PMID- 24588328
TI  - Chain-length-dependent autocatalytic hydrolysis of fatty acid anhydrides in
      polyethylene glycol.
AB  - Autocatalytic hydrolysis of fatty acid anhydrides induced by the spontaneously
      formed vesicles has been studied for years. However, whether the reaction
      autocatalyzed by vesicles formed in diluted solutions applies also to
      macromolecular crowded conditions remains unknown. The aim of this study is to
      characterize hydrolysis behavior of fatty acid anhydrides and formation of
      vesicles in crowded media. Inert macromolecular crowding agents such as
      polyethylene glycol (PEG) and Dextran were used to probe the impact of external
      crowding on the autocatalytic hydrolysis of fatty acid anhydrides with varied
      hydrophobic chain length. Under stringent conditions of crowding, hydrolysis
      rates of octanoic anhydride, nonanoic anhydride, and decanoic anhydride were
      found to decrease, but the rates of lauric anhydride and oleic anhydride
      increased. These results suggest that the effect of the crowding agent on the
      hydrolysis of fatty acid anhydrides was chain-length-dependent. Characterization
      of the size and polydispersity of vesicles formed from hydrolyzed fatty acid
      anhydrides in crowding revealed that long-chain fatty acids formed monodisperse
      vesicles easier at lower concentrations of PEG. Measurement of the critical
      aggregation concentration of ionized fatty acid in the presence of PEG showed
      that crowding media promoted vesicle formation from long-chain fatty acids but
      inhibited those from fatty acids with fewer carbon atoms. Further investigation
      of the diffusion property of ionized fatty acids in crowding agents suggested
      that PEG might create more hydrophobic areas for long-chain fatty acids
      anhydrides, which subsequently promoted the unreacted anhydride in the aqueous
      phase to be solubilized in the formed vesicles. This research provides
      information for understanding the autocatalytic reaction accompanied by self
      producing aggregates and the behavior of fatty acids in crowding media. 

PMID- 24588329
TI  - Working conditions of Iranian hand-sewn shoe workers and associations with
      musculoskeletal symptoms.
AB  - The working conditions and the prevalence of self-reported musculoskeletal
      symptoms among 180 Iranian hand-sewn shoe workers were evaluated in this cross
      sectional study. Data were collected using both questionnaire (for assessing
      musculoskeletal symptoms and associated risk factors) and direct observations of
      posture (by the Rapid Upper Limb Assessment [RULA] method). The prevalence and
      severity of symptoms was very high among the study population. The mean RULA
      grand score of 6.2 indicates that in most cases the workers' postures at their
      workstations need to be investigated and some changes are required immediately.
      Multiple logistic regression models indicated that the job experience, daily
      working hours, duration of continuous work without breaks, feeling pressure due
      to work and working postures were significantly associated with musculoskeletal
      symptoms of different body regions. The results are discussed in terms of their
      implications for hand-sewing tasks. These findings can help to better understand
      the working conditions of those jobs involving hand-sewing operation and
      highlight the potential for ergonomic interventions to reduce musculoskeletal
      symptoms among these working groups.

PMID- 24588330
TI  - A new method of securing the airway for differential lung ventilation in
      intensive care.
AB  - Differential lung ventilation to achieve optimised ventilation for each lung is a
      procedure rarely used in the intensive care unit, to treat select cases of severe
      unilateral lung disease in intensive care. However, existing techniques both for
      securing the airway and ventilating the lungs are challenging and have
      complications. We present the use of differential lung ventilation in the
      intensive care setting, securing the airway with a technique not previously
      described, using endotracheal tubes inserted through a tracheotomy and orally. In
      the course of 1 month, we treated three patients with unilateral atelectatic and
      consolidated lungs by differential lung ventilation. The left lung was ventilated
      through an endotracheal tube inserted into the left main stem bronchus through a
      tracheotomy. The right lung was ventilated through an endotracheal tube with the
      cuff positioned immediately under the vocal cord. In patient 1, the diseased lung
      remained consolidated after 24 h of differential lung ventilation. In the two
      other patients, the diseased lungs responded to differential lung ventilation by
      increased compliance and radiographic increased aeration. Differential
      ventilation of the lungs with this novel technique is feasible and may increase
      the likelihood of successful treatment of atelectatic lungs refractory to
      conventional ventilator strategies.

PMID- 24588331
TI  - Alkoxyboration: ring-closing addition of B-O sigma bonds across alkynes.
AB  - For nearly 70 years, the addition of boron-X sigma bonds to carbon-carbon
      multiple bonds has been employed in the preparation of organoboron reagents.
      However, the significantly higher strength of boron-oxygen bonds has thus far
      precluded their activation for addition, preventing a direct route to access a
      potentially valuable class of oxygen-containing organoboron reagents for
      divergent synthesis. We herein report the realization of an alkoxyboration
      reaction, the addition of boron-oxygen sigma bonds to alkynes. Functionalized O
      heterocyclic boronic acid derivatives are produced using this transformation,
      which is mild and exhibits broad functional group compatibility. Our results
      demonstrate activation of this boron-O sigma bond using a gold catalysis strategy
      that is fundamentally different from that used previously for other boron
      addition reactions. 

PMID- 24588332
TI  - Impact of socio-economic status on breast cancer screening in women with
      diabetes: a population-based study.
AB  - AIMS: There is evidence to suggest that mammography rates are decreased in women
      with diabetes and in women of lower socio-economic status. Given the strong
      association between low socio-economic status and diabetes, we explored the
      extent to which differences in socio-economic status explain lower mammography
      rates in women with diabetes. METHODS: A population-based retrospective cohort
      study in Ontario, Canada, of women aged 50 to 69 years with diabetes between 1999
      and 2010 age matched 1:2 to women without diabetes. Main outcome measure is the
      likelihood of at least one screening mammogram in women with diabetes within a 36
      month period, starting as of either 1 January 1999, their 50th birthday, or 2
      years after diabetes diagnosis--whichever came last. Outcomes were compared with
      those in women without diabetes during the same period as their matched
      counterparts, adjusting for socio-economic status based on neighbourhood income
      and other demographic and clinical variables. RESULTS: Of 504,288 women studied
      (188,759 with diabetes, 315,529 with no diabetes), 63.8% had a screening
      mammogram. Women with diabetes were significantly less likely to have a mammogram
      after adjustment for socio-economic status and other factors (odds ratio 0.79,
      95% CI 0.78-0.80). Diabetes was associated with lower mammogram use even in women
      from the highest socio-economic status quintile (odds ratio 0.79, 95% CI 0.75
      0.83). CONCLUSIONS: The presence of diabetes was an independent barrier to breast
      cancer screening, which was not explained by differences in socio-economic
      status. Interventions that target patient, provider, and health system factors
      are needed to improve cancer screening in this population.

PMID- 24588333
TI  - Development of the Nursing Community Apgar Questionnaire (NCAQ): a rural nurse
      recruitment and retention tool.
AB  - INTRODUCTION: Health professional shortages are a significant issue throughout
      the USA, particularly in rural communities. Filling nurse vacancies is a costly
      concern for many critical access hospitals (CAH), which serve as the primary
      source of health care for rural communities. CAHs and rural communities have
      strengths and weaknesses that affect their recruitment and retention of rural
      nurses. The purpose of this study was to develop a tool that rural communities
      and CAHs can utilize to assess their strengths and weaknesses related to nurse
      recruitment and retention. METHODS: The Nursing Community Apgar Questionnaire
      (NCAQ) was developed based on an extensive literature review, visits to multiple
      rural sites, and consultations with rural nurses, rural nurse administrators and
      content experts. RESULTS: A quantitative interview tool consisting of 50 factors
      that affect rural nurse recruitment and retention was developed. The tool allows
      participants to rate each factor in terms of advantage and importance level. The
      tool also includes three open-ended questions for qualitative analysis.
      CONCLUSIONS: The NCAQ was designed to identify rural communities' and CAHs'
      strengths and challenges related to rural nurse recruitment and retention. The
      NCAQ will be piloted and a database developed for CAHs to compare their results
      with those in the database. Furthermore, the NCAQ results may be utilized to
      prioritize resource allocation and tailor rural nurse recruitment and retention
      efforts to highlight a community's strengths. The NCAQ will function as a useful
      real-time tool for CAHs looking to assess and improve their rural nurse
      recruitment and retention practices and compare their results with those of their
      peers. Longitudinal results will allow CAHs and their communities to evaluate
      their progress over time. As the database grows in size, state, regional, and
      national results can be compared, trends may be discovered and best practices
      identified.

PMID- 24588335
TI  - Band mapping across a pn-junction in a nanorod by scanning tunneling microscopy.
AB  - We map band-edges across a pn-junction that was formed in a nanorod. We form a
      single junction between p-type Cu2S and n-type CdS through a controlled cationic
      exchange process of CdS nanorods. We characterize nanorods of the individual
      materials and the single junction in a nanorod with an ultrahigh vacuum scanning
      tunneling microscope (UHV-STM) at 77 K. From scanning tunneling spectroscopy and
      correspondingly the density of states (DOS) spectra, we determine the conduction
      and valence band-edges at different points across the junction and the individual
      nanorods. We could map the band-diagram of nanorod-junctions to bring out the
      salient features of a diode, such as p- and n-sections, band-bending, depletion
      region, albeit interestingly in the nanoscale. 

PMID- 24588336
TI  - The role of risk propensity in predicting self-employment.
AB  - This study aims to untangle the role of risk propensity as a predictor of self
      employment entry and self-employment survival. More specifically, it examines
      whether the potentially positive effect of risk propensity on the decision to
      become self-employed turns curvilinear when it comes to the survival of the
      business. Building on a longitudinal sample of 4,973 individuals from the German
      Socio-Economic Panel, we used event history analyses to evaluate the influence of
      risk propensity on self-employment over a 7-year time period. Results indicated
      that whereas high levels of risk propensity positively predicted the decision to
      become self-employed, the relationship between risk propensity and self
      employment survival followed an inverted U-shaped curve.

PMID- 24588337
TI  - Improvement in lung fibrosis using intravenous immunoglobulin in systemic
      sclerosis with myositis.

PMID- 24588338
TI  - EGFR-blockade with erlotinib reduces EGF and TGF-beta2 expression and the actin
      cytoskeleton which influences different aspects of cellular migration in lens
      epithelial cells.
AB  - INTRODUCTION: After cataract surgery, residual lens epithelial cells migrate and
      proliferate within the capsular bag resulting in posterior capsule opacification
      (PCO). The up-regulation of TGF-beta2, EGF and FGF-2 has been identified as a key
      factor in PCO pathogenesis leading to actin fiber assembly and alterations in the
      migration pattern. In this in vitro study, the influence of Erlotinib as a
      selective EGFR inhibitor is investigated on the cellular features indicated,
      which might promote a future clinical application. METHODS: Expression of EGF,
      FGF-2 and TGF-beta2 was measured using RT-PCR and ELISA in human lens epithelial
      cells (HLEC). Computational data of an in vitro time lapse microscopy assay were
      used for statistical analysis of single cell migration with a particular focus on
      cell-cell interaction; cell velocity distribution; and displacement before,
      during and after mitosis. The effect of Erlotinib on the actin-cytoskeleton was
      evaluated using Alexa Fluor 488 Phalloidin and epifluorescence microscopy.
      RESULTS: EGF and TGF-beta2 mRNA expression and protein levels are reduced by
      Erlotinib, while FGF-2 expression remained stable. Overall fluidity of cell-cell
      interaction is less in the presence of Erlotinib compared to the control and the
      velocity distribution across all cells becomes less uniform within the cell
      cluster. After mitosis, HLEC move significantly faster without EGFR inhibition,
      which can be completely blocked by Erlotinib. Furthermore, Erlotinib diminishes
      the amount of actin stress fibers and the stress fiber diameter. CONCLUSION: As a
      novel effect of Erlotinib on HLEC, we describe the down-regulation of EGF and TGF
      beta2 expression, both are crucial factors for PCO development. Cellular movement
      displays complex alterations under EGFR inhibition, which is partly explained by
      actin fiber depletion. These findings further underline the role of Erlotinib in
      pharmacologic PCO prophylaxis.

PMID- 24588339
TI  - Determinants of medication use in a multi-ethnic population of pregnant women: a
      cross-sectional study.
AB  - OBJECTIVES: To investigate determinants of medication use among multi-ethnic
      pregnant women. METHODS: A total of 641 pregnant women participated in this cross
      sectional study in a Brussels university hospital. A questionnaire was used to
      obtain data on socio-demographic characteristics and medication use. Chi-squared
      tests and binary logistic regression analyses were performed using SPSS 19.
      RESULTS: Medication use during pregnancy (37%) was positively associated with age
      older than 35 years, Western origin, being born in Belgium, high education and
      employment status. Highly educated Western women had a greater exposure to drugs
      with an unknown safety profile than Arab/Turkish and 'Other (non-Western)
      origins' women. In the latter two groups, low education and nulliparity were the
      most important determinants of lower drug use. Nulliparous Arab/Turkish women
      used significantly less medications (17%) during pregnancy than parous women with
      the same ethnic background (34%; p = 0.024). CONCLUSIONS: Medication use during
      pregnancy is considerable but differs according to ethnicity. Age, parity,
      educational level, occupational status and duration of stay in Belgium are
      important determinants that should be taken into account for risk assessment and
      preventive measures targeting pregnant women.

PMID- 24588341
TI  - Maternal and fetal IL1RN polymorphisms and the risk of preterm delivery: a meta
      analysis.
AB  - OBJECTIVE: The aim of this study is to assess the relationship between IL1RN*2
      variants and preterm delivery (PTD) risk. METHODS: Eligible studies were searched
      in Embase and PubMed databases from inception to November 2013. Two investigators
      identified relevant studies and extracted data of maternal and fetal genotype
      independently. Based on the evidence of functional studies, we used the dominant
      model to all compared studies. RESULTS: To maternal genotype, 269 PTDs and 688
      controls were included in meta-analysis. The overall combined odds ratio for the
      IL1RN*2 variant and PTD was 1.91 (95% CI, 1.41-2.58). To fetal genotype, five
      studies of 322 PTDs and 858 term controls were included. The result for fetal
      genotype analysis showed increased risk of PTD, but not significantly (OR 1.33,
      95% CI 0.99-1.78). Subgroup analysis indicated that both maternal and fetal
      carriage of IL1RN*2 increased the risk of PTD only in studies including preterm
      premature rupture of membranes (PPROM), with a pooled OR 2.02 (95% CI 1.44-2.85)
      and 1.42 (1.02-1.99), respectively. CONCLUSIONS: This meta-analysis suggests that
      maternal carriage of IL1RN*2 were associated with increased risk in PTD. PPROM
      may be an important confounding factor that should be taken into consideration
      for study of IL1RN polymorphism and PTD.

PMID- 24588340
TI  - Problem gamblers are hyposensitive to wins: an analysis of skin conductance
      responses during actual gambling on electronic gaming machines.
AB  - Physiological arousal is purportedly a key determinant in the development and
      maintenance of gambling behaviors, with problem gambling conceptualized in terms
      of abnormal autonomic responses. Theoretical conceptualizations of problem
      gambling are discordant regarding the nature of deficit in this disorder; some
      accounts posit that problem gamblers are hypersensitive to reward, and others
      that they are hyposensitive to reward and/or punishment. Previous research
      examining phasic electrodermal responses in gamblers has been limited to
      laboratory settings, and reactions to real gaming situations need to be examined.
      Skin conductance responses (SCRs) to losses, wins, and losses disguised as wins
      (LDWs) were recorded from 15 problem gamblers (PGs) and 15 nonproblem gamblers
      (NPGs) while they wagered their own money during electronic gaming machine play.
      PGs demonstrated significantly reduced SCRs to reward. SCRs to losses and LDWs
      did not differ for either PGs or NPGs. This hyposensitivity to wins may reflect
      abnormalities in incentive processing, and may represent a potential biological
      marker for problem gambling. 

PMID- 24588342
TI  - Systematic review with meta-analysis: meat consumption and the risk of
      hepatocellular carcinoma.
AB  - BACKGROUND: The association between meat consumption and the risk of
      hepatocellular carcinoma (HCC) is still inconclusive. AIM: To conduct a
      systematic review and meta-analysis to quantitatively assess the relationship
      between meat intake and the risk of HCC. METHODS: We searched the PubMed, Web of
      Science and EMBASE databases for relevant studies published before July 2013. The
      summary relative risks were pooled using the fixed-effects model when no
      substantial heterogeneity was detected, otherwise, the random-effects model was
      used. Heterogeneity and publication bias were also analysed. RESULTS: Finally,
      seven cohort studies and 10 case-control studies were included. The pooled
      relative risks (RRs) of HCC for the highest vs. lowest consumption levels were
      1.10 (95% confidence interval, CI: 0.85-1.42) for red meat, 1.01 (95% CI: 0.79
      1.28) for processed meat and 0.97 (95% CI: 0.85-1.11) for total meat. Moreover,
      white meat and fish consumption were found to be inversely associated with HCC
      risk, the summary RRs were 0.69 (95% CI: 0.58-0.81) and 0.78 (95% CI: 0.67-0.90)
      respectively, and the results remained quite stable after stratification by the
      confounding factors. CONCLUSIONS: The present meta-analysis indicates that a high
      level of white meat or fish consumption can reduce the risk of HCC significantly,
      while intake of red meat, processed meat or total meat is not associated with HCC
      risk. Our findings suggest that dietary intervention may be a promising approach
      for prevention of HCC, which still need to be confirmed by further well-designed
      prospective studies and experimental research.

PMID- 24588343
TI  - Pharmacokinetics and metabolism studies on the glucagon-like peptide-1 (GLP-1)
      derived metabolite GLP-1(9-36)amide in male Beagle dogs.
AB  - Glucagon-like peptide-1 (GLP-1)(7-36)amide is a 30-amino acid peptide hormone
      that is secreted from intestinal enteroendocrine L-cells in response to
      nutrients. GLP-1(7-36)amide possesses potent insulinotropic actions in the
      augmentation of glucose-dependent insulin secretion. GLP-1(7-36)amide is rapidly
      metabolized by dipeptidyl peptidase-IV to yield GLP-1(9-36)amide as the principal
      metabolite. Contrary to the earlier notion that peptide cleavage products of
      native GLP-1(7-36)amide [including GLP-1(9-36)amide] are pharmacologically
      inactive, recent studies have demonstrated cardioprotective and insulinomimetic
      effects with GLP-1(9-36)amide in mice, dogs and humans. In the present work, in
      vitro metabolism and pharmacokinetic properties of GLP-1(9-36)amide have been
      characterized in dogs, since this preclinical species has been used as an animal
      model to demonstrate the in vivo vasodilatory and cardioprotective effects of GLP
      1(9-36)amide. A liquid chromatography tandem mass spectrometry assay was
      developed for the quantitation of the intact peptide in hepatocyte incubations as
      opposed to a previously reported enzyme-linked immunosorbent assay. Although GLP
      1(9-36)amide was resistant to proteolytic cleavage in dog plasma and bovine serum
      albumin (t1/2>240 min), the peptide was rapidly metabolized in dog hepatocytes
      with a t1/2 of 110 min. Metabolite identification studies in dog hepatocytes
      revealed a variety of N-terminus cleavage products, most of which, have also been
      observed in human and mouse hepatocytes. Proteolysis at the C-terminus was not
      observed in GLP-1(9-36)amide. Following the administration of a single
      intravenous bolus dose (20 ug/kg) to male Beagle dogs, GLP-1(9-36)amide exhibited
      a mean plasma clearance of 15 ml/min/kg and a low steady state distribution
      volume of 0.05 l/kg, which translated into a short elimination half life of 0.05
      h. Following subcutaneous administration of GLP-1(9-36)amide at 50 ug/kg,
      systemic exposure of GLP-1(9-36)amide as ascertained from maximal plasma
      concentrations and area under the plasma concentration-time curve from zero to
      infinity was 44 ng/ml and 32 ng h/ml, respectively. The subcutaneous
      bioavailability of GLP-1(9-36)amide in dogs was 57%. Our findings raise the
      possibility that the cardioprotective effects of GLP-1(9-36)amide in the
      conscious dog model of pacing-induced heart failure might be due, at least in
      part, to the actions of additional downstream metabolites, which are obtained
      from proteolytic cleavage of the peptide backbone in the parent compound in the
      liver.

PMID- 24588344
TI  - Liquid chromatography mass spectrometry determination of mocetinostat (MGCD0103)
      in rat plasma and its application to a pharmacokinetic study.
AB  - Mocetinostat (MGCD0103) is a benzamide histone deacetylase inhibitor undergoing
      clinical trials for treatment of various cancers including Hodgkin's lymphoma,
      follicular lymphoma and acute myelogenous leukemia. A sensitive and selective
      liquid chromatography mass spectrometry method for determination of MGCD0103 in
      rat plasma was developed. After addition of midazolam as internal standard (IS),
      protein precipitation by acetonitrile was used as sample preparation.
      Chromatographic separation was achieved on a C18 (2.1 mm*50 mm, 3.5 um) column
      with acetonitrile-0.1% formic acid in water as mobile phase with gradient
      elution. An electrospray ionization source was applied and operated in positive
      ion mode; selective ion monitoring (SIM) mode was used for quantification using
      target fragment ions m/z 397 for MGCD0103 and m/z 326 for the IS. Calibration
      plots were linear over the range of 5-5000 ng/mL for MGCD0103 in rat plasma. Mean
      recoveries of MGCD0103 in rat plasma were in the range of 89.7-96.1%. RSD of
      intra-day and inter-day precision were both<11%. The accuracy of the method
      ranged from 96.5% to 109.7%. The matrix effects for MGCD0103 were between 94.5%
      and 97.4%. The method was successfully applied to pharmacokinetic study of
      MGCD0103 after oral (15 mg/kg) and intravenous (3 mg/kg) administration in rats.
      The bioavailability of MGCD0103 was 29.3% in rats.

PMID- 24588345
TI  - Illness representations predict adherence in adolescents and young adults with
      type 1 diabetes.
AB  - OBJECTIVE: Most adolescents and young adults (AYAs) with type 1 diabetes struggle
      with diabetes self-management and exhibit suboptimal glycemic control. This study
      examined two models of association between illness representations, a modifiable
      predictor of suboptimal outcomes, and adherence and glycemic control in AYAs with
      type 1 diabetes. DESIGN AND MAIN OUTCOME MEASURES: Ninety-nine AYAs (ages 15-20
      years) completed measures of illness representations and adherence at two visits.
      Blood glucose monitoring frequency and haemoglobin A1c were obtained via chart
      review. Relationships were examined using structural equation modelling. RESULTS:
      Illness representations accounted for a significant proportion of the variance in
      blood glucose monitoring frequency (DeltaR2 = .23, p < .01) and adherence to
      emergency precautions at Time 1 (DeltaR2 = .07, p = .03). Illness representations
      also accounted for significant variance in blood glucose monitoring frequency
      (DeltaR2 = .08, p = .01), adherence to recommendations for insulin and food
      (DeltaR2 = .08, p = .02) and exercise (DeltaR2 = .10, p < .01), and adherence to
      emergency precautions (DeltaR2)= .16, p < .01) at Time 2. CONCLUSION: Illness
      representations are salient predictors of adherence in this population.
      Interventions targeting adherence promotion and glycemic control in AYAs with
      type 1 diabetes may be enhanced by efforts to modify illness representations.

PMID- 24588347
TI  - Genetic variation and the evolution of epigenetic regulation.
AB  - Epigenetic variation has been observed in a range of organisms, leading to
      questions of the adaptive significance of this variation. In this study, we
      present a model to explore the ecological and genetic conditions that select for
      epigenetic regulation. We find that the rate of temporal environmental change is
      a key factor controlling the features of this evolution. When the environment
      fluctuates rapidly between states with different phenotypic optima, epigenetic
      regulation may evolve but we expect to observe low transgenerational inheritance
      of epigenetic states, whereas when this fluctuation occurs over longer time
      scales, regulation may evolve to generate epigenetic states that are inherited
      faithfully for many generations. In all cases, the underlying genetic variation
      at the epigenetically regulated locus is a crucial factor determining the range
      of conditions that allow for evolution of epigenetic mechanisms. 

PMID- 24588346
TI  - Blind prediction of binding affinities for charged supramolecular host-guest
      systems: achievements and shortcomings of DFT-D3.
AB  - Association free energies DeltaGa are calculated for two different types of host
      guest systems, the rigid cucurbit[7]uril (CB7) and the basket shaped octa-acid
      (OA), and a number of charged guest molecules each by quantum chemical methods
      from first principles in the context of a recent blind test challenge (SAMPL4).
      For CB7, the overall agreement between theory and experiment is excellent. In
      comparison with all other submitted calculated relative DeltaGa,rel values for
      this part of the blind test, our results ranked on top. Modeling the binding free
      energy in the case of the OA host mainly suffers from the problem that the
      binding situation is undefined with respect to the charge state and due to its
      intrinsic flexibility the host-guest complex is not represented well by a single
      configuration, but qualitative features of the binding process such as the proper
      binding orientation and the order of magnitude of DeltaGa are represented in
      accord with the experimental expectations even though an accurate ranking is not
      possible. 

PMID- 24588348
TI  - Cranial size variation and lineage diversity in early Pleistocene Homo.
AB  - A recent article in this journal concluded that a sample of early Pleistocene
      hominin crania assigned to genus Homo exhibits a pattern of size variation that
      is time dependent, with specimens from different time periods being more
      different from each other, on average, than are specimens from the same time
      period. The authors of this study argued that such a pattern is not consistent
      with the presence of multiple lineages within the sample, but rather supports the
      hypothesis that the fossils represent an anagenetically evolving lineage (i.e.,
      an evolutionary species). However, the multiple-lineage models considered in that
      study do not reflect the multiple-species alternatives that have been proposed
      for early Pleistocene Homo. Using simulated data sets, I show that fossil
      assemblages that contain multiple lineages can exhibit the time-dependent pattern
      of variation specified for the single-lineage model under certain conditions,
      particularly when temporal overlap among fossil specimens attributed to the
      lineages is limited. These results do not reject the single-lineage hypothesis,
      but they do indicate that rejection of multiple lineages in the early Pleistocene
      Homo fossil record is premature, and that other sources of variation, such as
      differences in cranial shape, should be considered. 

PMID- 24588349
TI  - Method for cellular imaging of palmitoylated proteins with clickable probes and
      proximity ligation applied to Hedgehog, tubulin, and Ras.
AB  - Hedgehog protein undergoes post-translational palmitoylation, which is critical
      for its signaling activity during embryonic development and in adult tissues. Due
      to a lack of suitable imaging methods, the trafficking route of palmitoylated
      Hedgehog has remained unclear in secretory cells. Here, we report a novel method
      for imaging the subcellular distribution of palmitoylated forms of cellular
      proteins with high resolution. The method utilizes clickable chemical reporters
      to label the entire palmitoylated proteome, followed by proximity ligation on
      antibodies to the click-conjugated dye and the protein of interest to reveal the
      spatial localization of specific palmitoylated proteins, as exemplified by sonic
      Hedgehog, tubulin, and Ras. Palmitoylated sonic Hedgehog is found in the
      endoplasmic reticulum, the Golgi apparatus, and at the plasma membrane but not
      the endosomal system in Hedgehog-secreting cells. Palmitoylated tubulin is found
      along microtubule tracks and also partially associated with the plasma membrane,
      while palmitoylated H-Ras is visualized at various cellular locations including
      the plasma membrane, Golgi apparatus and endoplasmic reticulum. Our method is
      broadly applicable to imaging the palmitoylation of cellular proteins as well as
      other protein post-translational modifications that are detectable by clickable
      chemical reporters. 

PMID- 24588351
TI  - Child Rights and Health Care: International Society for Social Pediatrics and
      Child Health (ISSOP) Position Statement.

PMID- 24588350
TI  - Consequences of adolescent or adult ethanol exposure on tone and context fear
      retention: effects of an acute ethanol challenge during conditioning.
AB  - BACKGROUND: An acute ethanol (EtOH) challenge prior to fear conditioning
      typically disrupts fear retention to contextual cues to a greater degree than
      fear retention to a discrete tone cue, and adolescent rats are less sensitive
      than adults to these EtOH-induced disruptions of context fear memory. Given that
      some research suggests that repeated EtOH exposure during adolescence may "lock
      in" adolescent-typical EtOH sensitivity into adulthood, the purpose of this study
      was to determine whether adults exposed to EtOH as adolescents would be less
      sensitive to EtOH-induced disruptions of context fear. METHODS: Male Sprague
      Dawley rats were given 4 g/kg intragastric EtOH (25% v/v) or water every 48 hours
      for a total of 11 exposures during adolescence (postnatal day [P] 28 to 48) or
      adulthood (P70-90). After a 22-day non-EtOH period, animals were acutely
      challenged with 1 g/kg intraperitoneal EtOH or saline 10 minutes prior to tone or
      context (noncued) fear conditioning. Tone and context fear retention was
      subsequently examined. RESULTS: Regardless of age or exposure history, typical
      deficits in context fear retention were evident after EtOH challenge during
      conditioning. Similarly, tone fear retention was disrupted in all animals that
      were trained in the presence of EtOH, which was somewhat surprising given the
      relative resistance of tone fear retention to an acute EtOH challenge.
      CONCLUSIONS: These results do not support the notion of a "lock-in" of adolescent
      typical EtOH sensitivity as there was no influence of exposure age on sensitivity
      to the disruptive effects of an acute EtOH challenge. Thus, it appears that not
      all adolescent-like EtOH sensitivities persist into adulthood after prior EtOH
      exposure during adolescence.

PMID- 24588352
TI  - Commentary on the ISSOP policy statement on the UNCRC and health.

PMID- 24588353
TI  - Coherent optical transitions in implanted nitrogen vacancy centers.
AB  - We report the observation of stable optical transitions in nitrogen-vacancy (NV)
      centers created by ion implantation. Using a combination of high temperature
      annealing and subsequent surface treatment, we reproducibly create NV centers
      with zero-phonon lines (ZPL) exhibiting spectral diffusion that is close to the
      lifetime-limited optical line width. The residual spectral diffusion is further
      reduced by using resonant optical pumping to maintain the NV(-) charge state.
      This approach allows for placement of NV centers with excellent optical coherence
      in a well-defined device layer, which is a crucial step in the development of
      diamond-based devices for quantum optics, nanophotonics, and quantum information
      science. 

PMID- 24588355
TI  - Is red the colour of danger? Testing an implicit red-danger association.
AB  - Research using participant's self-reports has documented a link between red and
      danger. In this research, we used two different variants of a Stroop word
      evaluation task to test for the possibility of an implicit red-danger association
      using carefully controlled colour stimuli (equated on lightness and chroma).
      Experiment 1, using words as stimuli, yielded strong evidence of a link between
      red and danger, and weaker evidence of a green-safety association. Experiment 2,
      using symbols as stimuli, again yielded strong evidence of a link between red and
      danger; no green effects were observed. The findings were discussed in terms of
      the power and promise of red in signal communication. 

PMID- 24588356
TI  - Infant abusive head trauma prevention: acceptability of the Period of PURPLE
      Crying(r) program in far North Queensland, Australia.
AB  - INTRODUCTION: A study examined the appropriateness and likelihood of usage of the
      north American Period of PURPLE Crying(r) intervention program in far north
      Queensland, to educate families about the risk of infant abusive head trauma
      (AHT)/shaken baby syndrome. METHODS: A mixed-method cross-sectional study with a
      questionnaire and semi-structured interview was conducted with 33 health
      professionals in far north Queensland (FNQ) to gauge their opinions of the Period
      of PURPLE Crying program's educational materials. RESULTS: Seventy per cent of
      participants were aware of infant AHT; 87.8% agreed the program would be
      appropriate for far north Queensland populations; 90% agreed that new
      parents/carers could learn new strategies to deal with inconsolable crying, and
      that men would be particularly advantaged. CONCLUSIONS: In their present form,
      the educational materials of the Period of PURPLE Crying are appropriate for use.
      As such, the researchers intend to undertake a pilot implementation in FNQ.

PMID- 24588354
TI  - Secrets of platelet exocytosis - what do we really know about platelet secretion
      mechanisms?
AB  - Upon activation by extracellular matrix components or soluble agonists, platelets
      release in excess of 300 active molecules from intracellular granules. Those
      factors can both activate further platelets and mediate a range of responses in
      other cells. The complex microenvironment of a growing thrombus, as well as
      platelets' roles in both physiological and pathological processes, require
      platelet secretion to be highly spatially and temporally regulated to ensure
      appropriate responses to a range of stimuli. However, how this regulation is
      achieved remains incompletely understood. In this review we outline the
      importance of regulated secretion in thrombosis as well as in 'novel' scenarios
      beyond haemostasis and give a detailed summary of what is known about the
      molecular mechanisms of platelet exocytosis. We also discuss a number of theories
      of how different cargoes could be released in a tightly orchestrated manner,
      allowing complex interactions between platelets and their environment.

PMID- 24588357
TI  - Contact angle hysteresis of non-flattened-top micro/nanostructures.
AB  - A two-dimensional (2D) thermodynamic model is proposed to predict the contact
      angle (CA) and contact angle hysteresis (CAH) of different types of surface
      geometries, particularly those with asperities having nonflattened tops. The
      model is evaluated by micro/nano sinusoidal and parabolic patterns fabricated by
      laser ablation. These microstructures are analyzed thermodynamically through the
      use of the Gibbs free energy to obtain the equilibrium contact angle (CA) and
      contact angle hysteresis (CAH). The effects of the geometrical details of two
      types of microstructures on maximizing the superhydrophobicity of the
      nanopatterned surface are also discussed in an attempt to design surfaces with
      desired and/or optimum wetting characteristics. The analysis of the various
      surfaces reveals the important geometrical parameters that may lead to the lotus
      effect (high CA > 150 degrees  and low CAH < 10 degrees ) or petal effect (high
      CA > 150 degrees  and high CAH ? 10 degrees ). 

PMID- 24588358
TI  - Sulfonyl fluorides as alternative to sulfonyl chlorides in parallel synthesis of
      aliphatic sulfonamides.
AB  - Two types of aliphatic sulfonyl halides (Cl versus F) were compared in parallel
      synthesis of sulfonamides derived from aliphatic amines. Aliphatic sulfonyl
      fluorides showed good results with amines bearing an additional functionality,
      while the corresponding chlorides failed. Both sulfonyl halides were effective in
      the reactions with amines having an easily accessible amino group. Aliphatic
      sulfonyl chlorides reacted efficiently with amines bearing sterically hindered
      amino group while the corresponding fluorides showed low activity.

PMID- 24588359
TI  - Etomidate--a review of robust evidence for its use in various clinical scenarios.
AB  - Etomidate is an intravenous hypnotic with a favourable clinical profile in
      haemodynamic high-risk scenarios. Currently, there is an active debate about the
      clinical significance of the drug's side effects and its overall risk-benefit
      ratio. Etomidate-induced transient adrenocortical suppression is well documented
      and has been associated with increased mortality in sepsis. In surgical patients
      at risk of hypotensive complications, however, a review of current literature
      provides no robust evidence to contraindicate a single-bolus etomidate induction.
      Large randomised controlled trials as well as additional observational data are
      required to compare safety of etomidate and its alternatives. 

PMID- 24588360
TI  - Comparison of morphology of bulbar conjunctival cells assessed by impression
      cytology versus scrape and smear methods.
AB  - PURPOSE: To assess the morphology of superficial bulbar conjunctival cells
      collected by impression cytology or by scraping. METHODS: Freshly procured sheep
      eyes from a slaughterhouse were washed and then conjunctival impression cytology
      (CIC) samples taken from the nasal aspect of the bulbar conjunctiva on a Biopore
      Millicell filter unit, or cells scraped from the same location and smeared onto
      glass slides. After alcohol fixation, all samples were stained with Giemsa. Cell
      images were obtained by light microscopy at 200* magnification, and subjected to
      morphometry. RESULTS: Cells obtained by scrape/smear processing appeared larger
      and less densely staining than cells procured by CIC. This appearance was
      confirmed by morphometry with measures of cell longest dimension LONG being 27.7
      +/- 1.3 MUm and 21.7 +/- 1.5 MUm, respectively, while cell AREAC measures
      averaged 543 +/- 42 MUm(2) and 333 +/- 51 MUm(2); these differences were
      significant (p < 0.001). Similarly, cell nucleus length (NUCLONG) and nucleus
      area (AREANUC) were also larger in smeared cells (p < 0.001). Various
      calculations of nucleo-cytoplasmic ratios as based on dimensions or area were
      only slightly different when comparing cells obtained by the two methods,
      indicating that the glass slide-smeared cells simply spread out more than cells
      on the CIC filters. CONCLUSIONS: Differences in cell and nucleus size can result
      from use of different processing methods. Therefore, in making comparisons
      between sets of conjunctival cells, it is important that cell collection and
      processing methods be considered.

PMID- 24588361
TI  - Severe macrophage activation syndrome and central nervous system involvement in
      juvenile dermatomyositis.

PMID- 24588362
TI  - Effect of peripheral cholinergic stimulation on autonomic modulation in Type 2
      diabetes with autonomic neuropathy: a randomized controlled trial.

PMID- 24588363
TI  - Influenza-like illness among Hong Kong Chinese pregnant women.
AB  - We assessed the self-reported prevalence of influenza-like illness (ILI) during
      pregnancy in two samples of 546 and 2764 new mothers who were pregnant during the
      2009-10 and 2010-11 peak influenza seasons. During pregnancy, 11% of participants
      experienced an ILI. Cough, sore throat and nasal congestion were the most common
      reported symptoms. Only 4.6% and 9% of the participants in sample 1 and 2 had an
      underlying chronic illness, respectively, and 3.3% of mothers in both groups were
      smokers. Conducting regular surveillance on influenza prevalence during pregnancy
      is essential to evaluate the costs and benefits of influenza vaccination
      programmes.

PMID- 24588364
TI  - KR-62980 suppresses lipid metabolism through inhibition of cytosolic NADP
      isocitrate dehydrogenase in zebrafish.
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma) is a target of
      antidiabetic drugs. However, many PPARgamma activators, including rosiglitazone,
      show unwanted side effects, such as weight gain. The KR-62980 [1-(trans
      methylimino-N-oxy)-3-phenyl-6-(3-phenylpropoxy)-1H-indene-2-carboxylic acid ethyl
      ester], a novel partial agonist of PPARgamma, is a new compound for diabetes with
      antihyperglycemic activity and weak antiadipogenic activity. This study was
      performed to elucidate the mechanism of the weak adipogenesis induced by KR-62980
      despite its being a PPARgamma agonist in zebrafish. We elucidated the mechanism
      of KR-62980 in lipid metabolism using adipocytes and zebrafish. Since NADPH is a
      critical cofactor in fat metabolism, we investigated effect of KR-62980 on NADPH
      producing enzymes such as cytosolic NADP(+) isocitrate dehydrogenase (cICDH). We
      found that the mRNA expression of cICDH was significantly decreased by KR-62980
      in 3T3-L1 cells. KR-62980 inhibited lipase activity and lipid metabolism in
      zebrafish. Further, KR-62980 substantially suppressed cICDH in adipocytes and
      zebrafish. These results suggest that cICDH may be one of the targets of KR-62980
      responsible for weight gain and adipogenesis.

PMID- 24588365
TI  - Effectiveness of job search interventions: a meta-analytic review.
AB  - The current meta-analytic review examined the effectiveness of job search
      interventions in facilitating job search success (i.e., obtaining employment).
      Major theoretical perspectives on job search interventions, including behavioral
      learning theory, theory of planned behavior, social cognitive theory, and coping
      theory, were reviewed and integrated to derive a taxonomy of critical job search
      intervention components. Summarizing the data from 47 experimentally or quasi
      experimentally evaluated job search interventions, we found that the odds of
      obtaining employment were 2.67 times higher for job seekers participating in job
      search interventions compared to job seekers in the control group, who did not
      participate in such intervention programs. Our moderator analysis also suggested
      that job search interventions that contained certain components, including
      teaching job search skills, improving self-presentation, boosting self-efficacy,
      encouraging proactivity, promoting goal setting, and enlisting social support,
      were more effective than interventions that did not include such components. More
      important, job search interventions effectively promoted employment only when
      both skill development and motivation enhancement were included. In addition, we
      found that job search interventions were more effective in helping younger and
      older (vs. middle-aged) job seekers, short-term (vs. long-term) unemployed job
      seekers, and job seekers with special needs and conditions (vs. job seekers in
      general) to find employment. Furthermore, meta-analytic path analysis revealed
      that increased job search skills, job search self-efficacy, and job search
      behaviors partially mediated the positive effect of job search interventions on
      obtaining employment. Theoretical and practical implications and future research
      directions are discussed.

PMID- 24588367
TI  - Air-oxidized linalool elicits eczema in allergic patients - a repeated open
      application test study.
AB  - BACKGROUND: Linalool is a commonly used fragrance terpene that forms potent
      sensitizers upon oxidation. In a recent multicentre study, we found that 7% of
      2900 patients showed positive patch test reactions to oxidized linalool at 6.0%.
      No elicitation studies have been performed. OBJECTIVE: To identify threshold
      concentrations for elicitation of allergic contact dermatitis caused by oxidized
      linalool in allergic individuals with repeated exposures. METHODS: Repeated open
      application tests were performed in 6 participants previously diagnosed with
      contact allergy to oxidized linalool. Creams containing 3.0%, 1.0% and 0.30%
      oxidized linalool (corresponding to 0.56%, 0.19% and 0.056% linalool
      hydroperoxides, respectively) and 'fine fragrance' containing 1.0%, 0.30% and
      0.10% oxidized linalool (corresponding to 0.19%, 0.056% and 0.019% linalool
      hydroperoxides, respectively) were used twice daily for up to 3 weeks. Patch
      testing with a dilution series of oxidized linalool was performed. RESULTS: Five
      of 6 participants reacted to the cream containing 3% oxidized linalool. With 1%
      oxidized linalool, a reaction was seen in 3 (cream) and 4 (fine fragrance)
      participants, respectively. With 0.3% oxidized linalool, 2 (cream) and 1 (fine
      fragrance) participants reacted. CONCLUSION: Repeated exposure to low
      concentrations of oxidized linalool can elicit allergic contact dermatitis in
      previously sensitized individuals.

PMID- 24588366
TI  - The integration of behavioral health interventions in children's health care:
      services, science, and suggestions.
AB  - Because the integration of mental or behavioral health services in pediatric
      primary care is a national priority, a description and evaluation of the
      interventions applied in the healthcare setting is warranted. This article
      examines several intervention research studies based on alternative models for
      delivering behavioral health care in conjunction with comprehensive pediatric
      care. This review describes the diverse methods applied to different clinical
      problems, such as brief mental health skills, clinical guidelines, and evidence
      based practices, and the empirical outcomes of this research literature. Next,
      several key treatment considerations are discussed to maximize the efficiency and
      effectiveness of these interventions. Some practical suggestions for overcoming
      key service barriers are provided to enhance the capacity of the practice to
      deliver behavioral health care. There is moderate empirical support for the
      feasibility, acceptability, and clinical utility of these interventions for
      treating internalizing and externalizing behavior problems. Practical strategies
      to extend this work and address methodological limitations are provided that draw
      upon recent frameworks designed to simplify the treatment enterprise (e.g.,
      common elements). Pediatric primary care has become an important venue for
      providing mental health services to children and adolescents due, in part, to its
      many desirable features (e.g., no stigma, local setting, familiar providers).
      Further adaptation of existing delivery models may promote the delivery of
      effective integrated interventions with primary care providers as partners
      designed to address mental health problems in pediatric healthcare. 

PMID- 24588368
TI  - Development of a standardized testing procedure for assessing the irritation
      potential of occupational skin cleansers.
AB  - BACKGROUND: Frequent skin cleaning fulfils the definition of occupational 'wet
      work'. Standardized methods are required to assess the irritation potential of
      workplace cleansers. OBJECTIVES: To develop a standardized procedure for testing
      the irritation potential of occupational skin cleansers. METHODS: In this single
      blind, single-centre trial in 25 healthy volunteers, the irritation potential of
      five generic reference cleansers was tested by three-times-daily washing with an
      automated skin cleaning device for 4 days, and quantification of cumulative skin
      barrier damage was performed by visual scoring, chromametry, transepidermal water
      loss TEWL, and corneometry. For two cleansers, reproducibility of the irritancy
      assessment was assessed. Furthermore, the irritation induced by four commercial
      workplace skin cleansers was studied. RESULTS: Whereas no significant changes
      were observed for any of the tested cleansers by either visual scoring or
      chromametry, significant increases in TEWL and significant decreases in stratum
      corneum hydration were found for all cleansers. Cleansers differed significantly
      in their irritation potential. On retesting of two cleansers, the first results
      were confirmed. Among the four commercial cleansers, one that was claimed to be
      mild was found to be disproportionally irritant. CONCLUSIONS: The presented model
      for testing cleansing preparations allows a highly controlled, practically
      relevant and reproducible irritancy assessment of occupational skin cleansers.

PMID- 24588369
TI  - Occupational allergic contact dermatitis caused by coconut fatty acids
      diethanolamide.
AB  - BACKGROUND: Coconut fatty acids diethanolamide [cocamide diethanolamine (cocamide
      DEA)] is a surface-active derivative of coconut oil that is used in industrial,
      household and cosmetic products. Cocamide DEA contact allergy has been reported
      relatively seldom. OBJECTIVES: To describe cocamide DEA-positive patients in an
      occupational dermatology clinic. METHODS: We retrieved allergic reactions to
      cocamide DEA from test files, and studied the occupation, exposure, concomitant
      allergic reactions and diagnoses of the positive patients. RESULTS: Of the 2572
      patients tested, 25 (1%) had an allergic reaction to cocamide DEA. Nineteen
      patients were occupational cases, and 11 worked in the metal industry. Hand
      cleansers constituted the main source of sensitization (n = 17). Other sources
      included two dishwashing liquids, one barrier cream, and one metalworking fluid.
      Three patients reacted to monoethanolamine and 2 to diethanolamine.
      Diethanolamine is an impurity of cocamide DEA, and can be found in cocamide DEA
      containing products and in commercial patch test substances, which may explain
      some concomitant reactions. CONCLUSIONS: Cocamide DEA allergy is relatively
      common in patients with occupational hand dermatitis, and mainly derives from
      hand cleansers. However, exposure to detergents, metalworking fluids and barrier
      creams must also be taken into account. Concomitant reactions to ethanolamines
      are possible.

PMID- 24588370
TI  - Allergic contact dermatitis caused by alkyl glucosides.
AB  - BACKGROUND: Alkyl glucosides were not expected to have a sensitizing potential at
      the concentrations to be used in finished consumer products; however, several
      contact allergy cases have been published. OBJECTIVES: To report on the patients
      suffering from allergic contact dermatitis caused by alkyl glucosides observed in
      our department. PATIENTS/METHODS: During a 19-year period (1993-2012), 11 842
      patients with suspected contact dermatitis were patch tested with the European
      baseline series and, if relevant, also with other series and individual
      allergens. For this study, the clinical data and the sensitization sources in the
      alkyl glucoside-positive patients were analysed. RESULTS: In total, 30 patients
      (24 women and 6 men) presented with a positive reaction to one or more alkyl
      glucosides. The causal products were shampoos (in 12), skin-cleansing products
      (in 12, among which were wipes for intimate hygiene), sunscreen products (in 5),
      skin-care products (in 4), and a deodorant (in 1). Sixteen patients showed
      multiple sensitivities (defined as three or more contact allergies), not only to
      other glucosides, but also to non-related chemicals. CONCLUSIONS: Allergic
      contact dermatitis caused by alkyl glucosides in cosmetics does occur, and might
      be more frequent than suspected. In view of their common use, their
      identification as allergenic culprits is important.

PMID- 24588371
TI  - Airborne allergic contact dermatitis caused by methylisothiazolinone in a child
      sensitized from wet wipes.

PMID- 24588372
TI  - An epidemic of contact allergy to methylisothiazolinone in Finland.

PMID- 24588373
TI  - Allergic chromium dermatitis from wearing 'chromium-free' footwear.

PMID- 24588374
TI  - Multicentre patch testing with fragrance mix II and hydroxyisohexyl 3-cyclohexene
      carboxaldehyde by the Swedish Contact Dermatitis Research Group.

PMID- 24588375
TI  - Sodium metabisulfite in blue jeans: an unexpected cause of textile contact
      dermatitis.

PMID- 24588376
TI  - New therapeutic options for advanced forms of thyroid cancer.
AB  - INTRODUCTION: While the vast majority of patients with thyroid cancer have an
      excellent prognosis, those with more aggressive courses experience significant
      morbidity and mortality. Advanced forms of thyroid cancer are typically
      refractory to standard therapy. Numerous agents with potential usefulness in the
      treatment of advanced thyroid cancer have recently come under study. AREAS
      COVERED: This article reviews agents identified through a systematic review of
      the scientific literature as being under investigation for treatment of advanced
      thyroid cancer. A search of both PubMed and the NCI Clinical Trials website was
      performed to identify such agents having reached Phase II or III testing.
      Improved understanding of cancer cell signaling pathways has led to the
      identification of > 500 kinases as potential therapeutic targets. Additional
      agents of interest include those that inhibit neoangiogenesis, alter epigenetic
      factors or stimulate antitumor immune reactions. While presently available agents
      have shown promise in improving progression-free survival (PFS), complete
      responses are not seen and significant adverse side effects are encountered.
      EXPERT OPINION: The development of numerous new anticancer agents holds the
      promise of treatment regimens that will extend PFS and ultimately overall
      survival in patients with advanced thyroid cancer. Anticipated future
      developments include individualized, multimodal treatment regimens based on
      specific tumor cell biology and driver mutations.

PMID- 24588378
TI  - Discrete-storm water-table fluctuation method to estimate episodic recharge.
AB  - We have developed a method to identify and quantify recharge episodes, along with
      their associated infiltration-related inputs, by a consistent, systematic
      procedure. Our algorithm partitions a time series of water levels into discrete
      recharge episodes and intervals of no episodic recharge. It correlates each
      recharge episode with a specific interval of rainfall, so storm characteristics
      such as intensity and duration can be associated with the amount of recharge that
      results. To be useful in humid climates, the algorithm evaluates the separability
      of events, so that those whose recharge cannot be associated with a single storm
      can be appropriately lumped together. Elements of this method that are subject to
      subjectivity in the application of hydrologic judgment are values of lag time,
      fluctuation tolerance, and master recession parameters. Because these are
      determined once for a given site, they do not contribute subjective influences
      affecting episode-to-episode comparisons. By centralizing the elements requiring
      scientific judgment, our method facilitates such comparisons by keeping the most
      subjective elements openly apparent, making it easy to maintain consistency. If
      applied to a period of data long enough to include recharge episodes with broadly
      diverse characteristics, the method has value for predicting how climatic
      alterations in the distribution of storm intensities and seasonal duration may
      affect recharge. 

PMID- 24588377
TI  - Does hangover influence the time to next drink? An investigation using ecological
      momentary assessment.
AB  - BACKGROUND: Measures of hangover are associated with current and future
      problematic alcohol use. At present, it is not known whether these associations
      reflect any direct influence of hangover events on near-term drinking behaviors.
      The current study aimed to determine whether hangover following a drinking
      episode influences time to next drink (TTND) and, if so, to determine the
      direction of this effect and identify any moderating personal or contextual
      factors. METHODS: Community-recruited, frequent drinkers oversampled for current
      smoking (N = 386) carried electronic diaries for 21 days, reporting on drinking
      behaviors and other experiences. Survival analysis was used to model data from
      2,276 drinking episodes, including 463 episodes that were followed by self
      reported hangover in morning diary entries. RESULTS: When tested as the sole
      predictor in a survival model, hangover was associated with increased TTND. The
      median survival time was approximately 6 hours longer after episodes with
      hangovers compared to those without. In a multivariate model, hangover was only
      significant in the presence of interaction effects involving craving at the end
      of the index drinking episode and the occurrence of financial stressors.
      Additional predictors of TTND in the final multivariate model included age,
      lifetime alcohol use disorder diagnosis, typical drinking frequency, day of the
      week, and morning reports of craving, negative affect, and stressors after the
      index episode. There was no association between morning reports of hangover and
      contemporaneous diary ratings of likelihood of drinking later the same day.
      CONCLUSIONS: The findings suggest that hangover has, at best, a modest or
      inconsistent influence on the timing of subsequent alcohol use among frequent
      drinkers.

PMID- 24588380
TI  - Efficient domino strategy for the synthesis of polyfunctionalized benzofuran
      4(5H)-ones and cinnoline-4-carboxamides.
AB  - An efficient, three-component strategy for the improved synthesis of
      multifunctionalized 6,7-dihydrobenzofuran-4(5H)-ones under microwave irradiation
      in ethyl alcohol within short periods has been established. The synthesized
      benzofuran-4(5H)-ones have been readily converted into polyfunctionalized
      cinnoline-4-carboxamides by treating with hydrazine hydratein in the same solvent
      through a regioselective ring-opening of the furan. Tedious workup procedures can
      be avoided because of the direct precipitation of products from the reaction
      solution by water addition, thus rendering the two-steps process ecofriendly. 

PMID- 24588381
TI  - Abstracts of the Annual Meeting of the Danish Pathology Society, 13-15 March
      2014, Herlev, Denmark.

PMID- 24588379
TI  - Pd-catalyzed alpha-arylation of alpha,alpha-difluoroketones with aryl bromides
      and chlorides. A route to difluoromethylarenes.
AB  - We report the Pd-catalyzed alpha-arylation of alpha,alpha-difluoroketones with
      aryl and heteroaryl bromides and chlorides catalyzed by an air- and moisture
      stable palladacyclic complex containing P(t-Bu)Cy2 as ligand. The combination of
      this Pd-catalyzed arylation and base-induced cleavage of the acyl-aryl C-C bond
      within the alpha-aryl-alpha,alpha-difluoroketone constitutes a one-pot, two-step
      procedure to synthesize difluoromethylarenes from aryl halides. A broad range of
      electronically varied aryl and heteroaryl bromides and chlorides underwent these
      two transformations, providing alpha-aryl-alpha,alpha-difluoroketones,
      difluoromethylarenes, and difluoromethylheteroarenes in high yields. 

PMID- 24588382
TI  - Aqueous poly(amidoamine) dendrimer G3 and G4 generations with several interior
      cores at pHs 5 and 7: a molecular dynamics simulation study.
AB  - Poly(amidoamine) (PAMAM) dendrimers play an important role in drug delivery
      systems, because the dendrimers are susceptible to gain unique features with
      modification of their structure such as changing their terminals or improving
      their interior core. To investigate the core improvement and the effect of core
      nature on PAMAM dendrimers, we studied two generations G3 and G4 PAMAM dendrimers
      with the interior cores of commonly used ethylendiamine (EDA), 1,5-diaminohexane
      (DAH), and bis(3-aminopropyl) ether (BAPE) solvated in water, as an aqueous
      dendrimer system, by using molecular dynamics simulation and applying a coarse
      grained (CG) dendrimer force field. To consider the electrostatic interactions,
      the simulations were performed at two protonation states, pHs 5 and 7. The
      results indicated that the core improvement of PAMAM dendrimers with DAH produces
      the largest size for G3 and G4 dendrimers at both pHs 5 and 7. The increase in
      the size was also observed for BAPE core but it was not so significant as that
      for DAH core. By considering the internal structure of dendrimers, it was found
      that PAMAM dendrimer shell with DAH core had more cavities than with BAPE core at
      both pHs 5 and 7. Also the moment of inertia calculations showed that the
      generation G3 is more open-shaped and has higher structural asymmetry than the
      generation G4. Possessing these properties by G3, specially due to its structural
      asymmetry, make penetration of water beads into the dendrimer feasible. But for
      higher generation G4 with its relatively structural symmetry, the encapsulation
      efficiency for water molecules can be enhanced by changing its core to DAH or
      BAPE. It is also observed that for the higher generation G4 the effect of core
      modification is more profound than G3 because the core modification promotes the
      structural asymmetry development of G4 more significantly. Comparing the number
      of water beads that penetrate into the PAMAM dendrimers for EDA, DAH, and BAPE
      cores indicates a significant increase when their cores have been modified with
      DAH or BAPE and substantiates the effective influence of the core nature in the
      dendrimer encapsulation efficiency. 

PMID- 24588383
TI  - Detectable CD8 cells correlate with improved overall survival in adult B
      lymphoblastic leukaemia patients.

PMID- 24588384
TI  - Recombinant expression of antimicrobial peptides using a novel self-cleaving
      aggregation tag in Escherichia coli.
AB  - Antimicrobial peptides (AMPs) are part of the innate immune system of complex
      multicellular organisms. Despite the fact that AMPs show great potential as a
      novel class of antibiotics, the lack of a cost-effective means for their mass
      production limits both basic research and clinical use. In this work, we describe
      a novel expression system for the production of antimicrobial peptides in
      Escherichia coli by combining DeltaI-CM mini-intein with the self-assembling
      amphipathic peptide 18A to drive the formation of active aggregates. Two AMPs,
      human beta-defensin 2 and LL-37, were fused to the self-cleaving tag and
      expressed as active protein aggregates. The active aggregates were recovered by
      centrifugation and the intact antimicrobial peptides were released into solution
      by an intein-mediated cleavage reaction in cleaving buffer (phosphate-buffered
      saline supplemented with 40 mmol/L Bis-Tris, 2 mmol/L EDTA, pH 6.2). The peptides
      were further purified by cation-exchange chromatography. Peptides yields of 0.82
      +/- 0.24 and 0.59 +/- 0.11 mg/L were achieved for human beta-defensin 2 and LL
      37, respectively, with demonstrated antimicrobial activity. Using our expression
      system, intact antimicrobial peptides were recovered by simple centrifugation
      from active protein aggregates after the intein-mediated cleavage reaction. Thus,
      we provide an economical and efficient way to produce intact antimicrobial
      peptides in E. coli. 

PMID- 24588385
TI  - Changes in the proteome of the cadmium-tolerant bacteria Cupriavidus taiwanensis
      KKU2500-3 in response to cadmium toxicity.
AB  - Cupriavidus taiwanensis KKU2500-3 is a cadmium (Cd)-tolerant bacterial strain
      that was previously isolated from rice fields contaminated with high levels of
      Cd. In 500 MUmol/L CdCl2, the KKU2500-3 strain grew slower and with a more
      prolonged lag-phase than when grown in the absence of Cd. A proteomic approach
      was used to characterize the protein expression in the Cd-tolerant bacteria C.
      taiwanensis KKU2500-3 during growth under Cd stress. When compared with the
      untreated cells, a total of 982 differentially expressed protein spots were
      observed in the CdCl2-treated cells, and 59 and 10 spots exhibited >2- and >4
      fold changes, respectively. The level of up- and downregulation varied from 2.01-
      to 11.26-fold and from 2.01- to 5.34-fold, respectively. Of the 33 differentially
      expressed protein spots analyzed by MALDI TOF MS/MS, 19 spots were successfully
      identified, many of which were involved in stress responses. The most highly
      upregulated protein (+7.95-fold) identified was the chaperone GroEL, which
      indicated that this factor likely contributed to the bacterial survival and
      growth in response to Cd toxicity. Detection of the downregulated protein
      flagellin (-3.52-fold) was consistent with the less effective ATP-mediated and
      flagella-driven motility. The flagella-losing cells were also observed in the Cd
      treated bacteria when analyzed by scanning electron microscopy. Thus, the Cd
      stressed cells may downregulate pathways involving ATP utilization in favor of
      other mechanisms in response to Cd toxicity. When the KKU2500-3 strain was grown
      in the presence of Cd, H2S was not detected, suggesting a possible role of the
      sulfur in precipitation with Cd. Apart from a general response, no specific
      process could be determined using the present proteomic approach. However, the
      potential role of protein folding-mediated GroEL, flagella-mediated motility and
      CdS biotransformation in Cd toxicity response observed in this study as well as
      the extent of Cd-tolerant mechanisms using other methods could facilitate the
      future application of this strain in addressing Cd environmental contamination. 

PMID- 24588386
TI  - The global regulator GacS regulates biofilm formation in Pseudomonas chlororaphis
      O6 differently with carbon source.
AB  - An aggressive root colonizer, Pseudomonas chlororaphis O6 produces various
      secondary metabolites that impact plant health. The sensor kinase GacS is a key
      regulator of the expression of biocontrol-related traits. Biofilm formation is
      one such trait because of its role in root surface colonization. This paper
      focuses on the effects of carbon source on biofilm formation. In comparison with
      the wild type, a gacS mutant formed biofilms at a reduced level with sucrose as
      the major carbon source but at much higher level with mannitol in the defined
      medium. Biofilm formation by the gacS mutant occurred without phenazine
      production and in the absence of normal levels of acyl homoserine lactones, which
      promote biofilms with other pseudomonads. Colonization of tomato roots was
      similar for the wild type and gacS mutant, showing that any differences in
      biofilm formation in the rhizosphere were not of consequence under the tested
      conditions. The reduced ability of the gacS mutant to induce systemic resistance
      against tomato leaf mold and tomato gray mold was consistent with a lack of
      production of effectors, such as phenazines. These results demonstrated
      plasticity in biofilm formation and root colonization in the rhizosphere by a
      beneficial pseudomonad. 

PMID- 24588387
TI  - Growth and bile tolerance of Lactobacillus brevis strains isolated from Japanese
      pickles in artificial digestive juices and contribution of cell-bound
      exopolysaccharide to cell aggregation.
AB  - Cell-bound exopolysaccharide (EPS) of the aggregable strain Lactobacillus brevis
      KB290 isolated from traditional Japanese pickles has been reported to protect
      against the effects of bile. However, there are no reports of bile tolerance
      mechanisms for other L. brevis strains that have aggregability. To elucidate the
      mechanism of bile tolerance of L. brevis KB290, we found 8 aggregable L. brevis
      strains out of 121 L. brevis strains isolated from traditional Japanese fermented
      pickles. We estimated their growth in artificial digestive juice and the amount
      of cell-bound EPS. We found 3 types of aggregation for these strains: filiform
      (<1 mm), medium floc (1-5 mm), or large floc (>5 mm). There was no significant
      difference in growth between nonaggregable and aggregable strains in the
      artificial digestive juice. The large floc strains selected from the aggregation
      strains showed significantly higher growth in the artificial digestive juice than
      nonaggregable strains. In medium and large floc strains, cell-bound EPS, mainly
      consisting of glucose, N-acetylglucosamine, and N-acetylmannosamine, were
      observed. The amount of EPS and each strain's growth index showed a positive
      correlation. We conclude that aggregable L. brevis strains were also protected by
      cell-bound EPS. 

PMID- 24588388
TI  - Something old, something new: revisiting natural products in antibiotic drug
      discovery.
AB  - Antibiotic discovery is in crisis. Despite a growing need for new drugs resulting
      from the increasing number of multi-antibiotic-resistant pathogens, there have
      been only a handful of new antibiotics approved for clinical use in the past 2
      decades. Faced with scientific, economic, and regulatory challenges, the
      pharmaceutical sector seems unable to respond to what has been called an
      "apocalyptic" threat. Natural products produced by bacteria and fungi are
      genetically encoded products of natural selection that have been the mainstay
      sources of the antibiotics in current clinical use. The pharmaceutical industry
      has largely abandoned these compounds in favor of large libraries of synthetic
      molecules because of difficulties in identifying new natural product antibiotics
      scaffolds. Advances in next-generation genome sequencing, bioinformatics, and
      analytical chemistry are combining to overcome barriers to natural products.
      Coupled with new strategies in antibiotic discovery, including inhibition of
      resistance, novel drug combinations, and new targets, natural products are poised
      for a renaissance to address what is a pressing health care crisis. 

PMID- 24588389
TI  - Mucin inhibits Pseudomonas aeruginosa biofilm formation by significantly
      enhancing twitching motility.
AB  - In Pseudomonas aeruginosa, type IV pili (TFP)-dependent twitching motility is
      required for development of surface-attached biofilm (SABF), yet excessive
      twitching motility is detrimental once SABF is established. In this study, we
      show that mucin significantly enhanced twitching motility and decreased SABF
      formation in strain PAO1 and other P. aeruginosa strains in a concentration
      dependent manner. Mucin also disrupted partially established SABF. Our analyses
      revealed that mucin increased the amount of surface pilin and enhanced
      transcription of the pilin structural gene pilA. Mucin failed to enhance
      twitching motility in P. aeruginosa mutants defective in genes within the pilin
      biogenesis operons pilGHI/pilJK-chpA-E. Furthermore, mucin did not enhance
      twitching motility nor reduce biofilm development by chelating iron. We also
      examined the role of the virulence factor regulator Vfr in the effect of mucin.
      In the presence or absence of mucin, PAODeltavfr produced a significantly reduced
      SABF. However, mucin partially complemented the twitching motility defect of
      PAODeltavfr. These results suggest that mucin interferes with SABF formation at
      specific concentrations by enhancing TFP synthesis and twitching motility, that
      this effect, which is iron-independent, requires functional Vfr, and only part of
      the Vfr-dependent effect of mucin on SABF development occurs through twitching
      motility. 

PMID- 24588391
TI  - Cyclic enterobacterial common antigens from Escherichia coli O157 as microbe
      associated molecular patterns.
AB  - In a previous study, we described 2 forms of cyclic enterobacterial common
      antigen (ECACYC), a tetramer and a pentamer, from Escherichia coli O157. ECACYC
      is present in several representatives of the Enterobacteriaceae. To date,
      functional studies on ECACYC are sparse. Cyclic oligosaccharides in other
      bacteria, like the cyclic beta-glucans in Rhizobiaceae, represent microbe
      associated molecular patterns involved in host-bacteria interaction. This
      observation determined the aim of the present study: to test whether the
      tetrameric and pentameric ECACYC from E. coli O157 can be recognised by host
      humoral and cellular mechanisms. ELISA tests designed to compare the 2 ECACYC
      with the O157 lipopolysaccharide showed that both ECACYC were not recognised by
      polyclonal anti-O157 serum but were good ligands for mannan-binding lectin. The
      lectin had a higher affinity for the tetramer than the pentamer. ECACYC deposited
      more C3b than did the lipopolysaccharide. To examine the interactions with human
      circulating neutrophils, the antigens were loaded onto fluorescent latex beads
      and applied in a phagocytosis experiment. Spheres coated with the 2 ECACYC
      occasionally adhered to phagocyte surfaces but, unlike O157-loaded spheres,
      failed to induce free-radical release. The results show that the 2 ECACYC
      represent microbe-associated molecular patterns recognised by host humoral non
      self-recognition mechanisms. 

PMID- 24588390
TI  - Recovery of novel alkaline phosphatase-encoding genes (phoX) from eutrophic Lake
      Taihu.
AB  - To expand current knowledge on the molecular aspects of alkaline phosphatase PhoX
      in shallow eutrophic freshwaters, we investigated the genetic diversity and
      abundance of the PhoX-encoding gene (phoX) in 4 ecological regions in Lake Taihu,
      China, following a gradient in total phosphorus concentrations ranging from
      hypereutrophic to mesotrophic. Bacterial phoX was heterogeneously distributed
      with the highest diversity in the eutrophic regions and the highest abundance in
      the mesotrophic Xukou Bay. The concentrations of total phosphorus and
      enzymatically hydrolyzable phosphorus determined the distribution of bacterial
      phoX in Lake Taihu. Most (70.8%) of the phoX-translated proteins had <90%
      similarity to the PhoX proteins in the GenBank database, suggesting the presence
      of novel phoX genotypes in Lake Taihu. The low overlap in phoX genotypes (15.8%)
      between Lake Taihu and some marine ecosystems, and the dominance of the
      translated proteins most similar to the Alphaproteobacteria-affiliated PhoX,
      demonstrate the uniqueness of PhoX in eutrophic freshwaters. 

PMID- 24588392
TI  - Serotype-associated polymorphisms in a partial rpoB gene sequence of Salmonella
      enterica.
AB  - Salmonella enterica is a zoonotic bacterium with more than 2500 serotypes, which
      affect a wide range of hosts and produce diverse clinical outcomes. Strain
      identification usually involves costly and time-demanding procedures. This paper
      describes the sequencing of a rpoB hypervariable gene segment (847 bp) that
      allows identification of serotypes in S. enterica strains isolated from several
      hosts. The nucleotide similarity values among S. enterica serotypes ranged from
      98.23% to 99.88%, with potential usefulness for devising a simple one-step
      sequencing as a first approach for identification of S. enterica strains. In
      conclusion, the analysis of polymorphisms in the partial rpoB sequence can
      discriminate S. enterica strains at the subspecies level. 

PMID- 24588393
TI  - Dexmedetomidine for preventing sevoflurane-related emergence agitation in
      children: a meta-analysis of randomized controlled trials.
AB  - Emergence agitation (EA) is a common problem after sevoflurane anesthesia in
      children. Prophylactic dexmedetomidine has been directed at this issue; however,
      the efficacy remains controversial. We therefore conducted a meta-analysis of
      randomized controlled trials (RCTs) to evaluate the effectiveness of
      dexmedetomidine on the incidence of sevoflurane-related EA. A comprehensive
      literature search was performed to identify RCTs that compared dexmedetomidine
      with placebo about the reduction in the incidence of sevoflurane-related EA for
      children. Heterogeneity between studies was anticipated; therefore, random
      effects models were chosen to calculate the pooled risk ratio (RR) and 95%
      confidence interval (CI), and I(2) statistics were used to assess statistical
      heterogeneity. The funnel plot and Egger test were used to assess potential
      publication bias. Subgroup analysis was run to explore the possible effects of
      age, surgical procedure, regional block/local anesthetics, supplemental
      analgesic, propofol, N2O, pre-medication and methodological quality on the
      incidence of EA using dexemedetomidine. Totally, 15 RCTs were included (518
      patients received dexmedetomidine and 413 had placebo). Dexmedetomidine reduced
      the incidence of sevofurane-related EA (pooled RR = 0.351; 95% CI: 0.275-0.449; P
      = 0.965; heterogeneity test, I(2) = 0.0%), and it also resulted in a lower
      incidence of severe EA (pooled RR = 0.119; 95% CI: 0.033-0.422; P = 0.962;
      heterogeneity test, I(2) = 0.0%). All subgroup analyses for potential sources of
      heterogeneity showed a lower incidence of sevoflurane-related EA after
      dexmedetomidine administration. This meta-analysis demonstrated that
      dexemedetomidine was effective in reducing the incidence of sevoflurane-induced
      EA in children as compared with placebo.

PMID- 24588394
TI  - Rhodium(III)-catalyzed redox-neutral C-H arylation via rearomatization.
AB  - Rhodium(III)-catalyzed arylation of arenes bearing a chelating group has been
      realized via a redox-economy process using 4-hydroxycyclohexa-2,5-dienones as the
      arylating reagents, leading to the synthesis of 3-arylated phenols. This redox
      neutral process proceeds via a C-H activation pathway with rearomatization being
      the driving force. 

PMID- 24588395
TI  - Graphene-based nanowire supercapacitors.
AB  - We present a new type of electrochemical supercapacitors based on graphene
      nanowires. Graphene oxide (GO)/polypyrrole (PPy) nanowires are prepared via
      electrodepostion of GO/PPy composite into a micoroporous Al2O3 template, followed
      by the removal of template. PPy is electrochemically doped by oxygen-containing
      functional groups of the GO to enhance the charging/discharging rates of the
      supercapacitor. A high capacitance 960 F g(-1) of the GO/PPy nanowires is
      obtained due to the large surface area of the vertically aligned nanowires and
      the intimate contact between the nanowires and the substrate electrode. The
      capacitive performance remains stable after charging and discharging for 300
      cycles. To improve the thermal stability and long-term charge storage, GO is
      further electrochemically reduced into graphene and PPy is subsequently thermally
      carbonized, leading to a high capacitance of 200 F g(-1) for the resultant pure
      reduced graphene oxide/carbon based nanowire supercapacitor. This value of
      capacitance (200 F g(-1)) is higher than that of conventional porous carbon
      materials while the reduced graphene oxide/carbon nanowires show a lower Faraday
      resistance and higher thermal stability than the GO/PPy nanowires. 

PMID- 24588396
TI  - Effect of embryonic development on the chicken egg yolk plasma proteome after 12
      days of incubation.
AB  - To better appreciate the dynamics of yolk proteins during embryonic development,
      we analyzed the protein quantitative changes occurring in the yolk plasma at the
      day of lay and after 12 days of incubation, by comparing unfertilized and
      fertilized chicken eggs. Of the 127 identified proteins, 69 showed relative
      abundance differences among conditions. Alpha-fetoprotein and two uncharacterized
      proteins (F1NHB8 and F1NMM2) were identified for the first time in the egg. After
      12 days of incubation, five proteins (vitronectin, alpha-fetoprotein, similar to
      thrombin, apolipoprotein B, and apovitellenin-1) showed a major increase in
      relative abundance, whereas 15 proteins showed a significant decrease in the
      yolks of fertilized eggs. In unfertilized/table eggs, we observed an accumulation
      of proteins likely to originate from other egg compartments during incubation.
      This study provides basic knowledge on the utilization of egg yolk proteins by
      the embryo and gives some insight into how storage can affect egg quality. 

PMID- 24588397
TI  - Circadian clock mediates light/dark preference in zebrafish (Danio rerio).
AB  - Zebrafish (Danio rerio) has been a widely used vertebrate animal model in
      developmental biology and behavioral neuroscience, but knowledge about some of
      its basic behaviors, for example, light/dark preference, is still controversial.
      Appropriate preference for light or dark environments can be crucial for an
      animal's survival, so we hypothesize that zebrafish may have its light/dark
      preference varied with the circadian clock. In this present work, we tested the
      hypothesis by recording the light/dark preference in a two-compartment tank
      continuously for over 60 h. We found that the light avoidance of fish generally
      increases with time from morning (8:00am) to midnight (2:00am), and then
      decreases with time from midnight (2:00am) to morning (8:00am), exhibiting a
      clear circadian-like trend in the light/dark preference. As melatonin can mediate
      circadian clock output and promote sleep in zebrafish, by adding extra melatonin
      at around 9:00am on the third day, the mean proportion of time fish spent in the
      dark area was increased significantly. Our results demonstrate that the circadian
      clock plays a significant role in regulating the light/dark preference in
      zebrafish, which provides valuable insights into understanding the metabolism
      mechanism underlying the neurobehavior, and facilitate further studies related to
      the neurobiology of normal and pathological behavior.

PMID- 24588398
TI  - Emerging biological therapies for systemic lupus erythematosus.
AB  - INTRODUCTION: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease
      with unpredictable disease course, intermingled with periods of remission and
      exacerbation. Current therapies for SLE are not ideal in terms of efficacy and
      toxicity. Although the prognosis of the disease has improved in the past decades,
      further improvement is hindered by the occurrence of organ damage as a result of
      persistent disease activity and treatment-related complications. Novel biological
      therapies targeting at higher treatment efficacy and fewer adverse effects are
      being developed. AREAS COVERED: This review summarizes recent data on novel
      biological therapies for SLE. The pitfalls of clinical trial design and future
      directions of the development of SLE therapeutics are discussed. EXPERT OPINION:
      The variable therapeutic response observed in SLE reflects the clinical and
      immunological heterogeneity of the disease. The treatment plan of SLE patients
      should be individualized, with the target of quenching out disease activity,
      minimizing disease flares, and treatment related morbidities. Despite the
      disappointment of recent clinical trials, avenues are being opened for novel
      agents that intervene at different levels of the pathophysiological cascade of
      SLE. With the availability of a new treatment armamentarium, it is hoped that the
      survival rate and quality of life of SLE patients can continue to improve.

PMID- 24588400
TI  - Mental health and parenting in rural areas: an exploration of parental
      experiences and current needs.
AB  - BACKGROUND: Research on parental mental health problems (MHPs) has predominantly
      used urban samples and focused on the risks for children. AIMS: The purpose of
      this study was to explore rural parents' lived experiences of parenting with a
      MHP. METHOD: Six semi-structured interviews were conducted with mothers who were
      using a mental health service in rural Ireland. Interpretative phenomenological
      analysis (IPA) was employed. RESULTS: Themes identified were: "Being Observed and
      Negatively Judged by Others"; "Overshadowed by the Duality of Parenting and
      MHPs"; "Dominance of Medication Over Other Treatment Options"; "Uncertainty (of
      Impact on Parenting Ability and Children)" and "Need for Inclusion". Although
      parents' experienced a variety of concerns generic to parenting and mental
      health, living in a small, rural community was related to pronounced concerns
      regarding the stigma, devaluation and uncertainty associated with MHPs and
      service use. CONCLUSION: Further investigation into and consideration for the
      specific needs and experiences of parent service-users could benefit both parents
      and their families and inform service development.

PMID- 24588401
TI  - Clarifying the measurement and the role of the behavioral inhibition system in
      alcohol misuse.
AB  - BACKGROUND: In response to conflicting reward (Behavioral Approach System [BAS])
      and/or punishment cues (Fight-Flight-Freeze System [FFFS]) the Behavioral
      Inhibition System (BIS) inhibits behavior, leading to increased attention to
      threat, high anxiety, and behavioral ambivalence. The role of BIS in alcohol
      misuse is complex, as anxiety promotes self-medication drinking, while attention
      to threat (e.g., negative outcomes of heavy drinking) may reduce risk. Theory
      suggests that a concurrent strong BAS may bias BIS-conflict in favor of alcohol
      approach, while a concurrent strong FFFS may increase the likelihood of alcohol
      avoidance. However, few studies measure BIS as a conflict system, and no studies
      incorporate such a measure into examinations of alcohol misuse. Our study goals
      were to (i) test the Motivational Flanker Task (MFT) as a new laboratory measure
      of the BIS, BAS, and FFFS; and (ii) use the MFT, in conjunction with self-report
      measures, to test BAS and FFFS as moderators of the BIS-alcohol misuse relation.
      We hypothesized that an elevated BIS would predict heavy drinking and alcohol
      related problems, but only when BAS was high. Further, we expected an elevated
      BIS to be associated with reduced alcohol misuse, but only when FFFS was high.
      METHODS: Students (N = 198) completed self-reports of BIS/BAS/FFFS and drinking
      behavior, and 2 reaction time tasks: MFT and Point Scoring Reaction Time Task
      (PSRTT). The PSRTT is a published measure of the revised BIS. RESULTS: MFT BIS
      conflict was associated with self-report and PSRTT measures. MFT BAS, but not
      FFFS, was associated with self-reports. As expected, elevated BIS was associated
      with heavy drinking, but only when BAS-Drive and BAS-Fun Seeking was also high.
      FFFS was not supported as a moderator of the BIS-alcohol misuse association.
      CONCLUSIONS: Results support the MFT as a promising measure of the revised BIS.
      Considering the joint effects of BIS and BAS clarified risk for alcohol misuse.

PMID- 24588399
TI  - Highly efficient macromolecule-sized poration of lipid bilayers by a
      synthetically evolved peptide.
AB  - Peptides that self-assemble, at low concentration, into bilayer-spanning pores
      which allow the passage of macromolecules would be beneficial in multiple areas
      of biotechnology. However, there are few, if any, natural or designed peptides
      that have this property. Here we show that the 26-residue peptide "MelP5", a
      synthetically evolved gain-of-function variant of the bee venom lytic peptide
      melittin identified in a high-throughput screen for small molecule leakage,
      enables the passage of macromolecules across bilayers under conditions where
      melittin and other pore-forming peptides do not. In surface-supported bilayers,
      MelP5 forms unusually high conductance, equilibrium pores at peptide:lipid ratios
      as low as 1:25000. The increase in bilayer conductance due to MelP5 is
      dramatically higher, per peptide, than the increase due to the parent sequence of
      melittin or other peptide pore formers. Here we also develop two novel assays for
      macromolecule leakage from vesicles, and we use them to characterize MelP5 pores
      in bilayers. We show that MelP5 allows the passage of macromolecules across
      vesicle membranes at peptide:lipid ratios as low as 1:500, and under conditions
      where neither osmotic lysis nor gross vesicle destabilization occur. The
      macromolecule-sized, equilibrium pores formed by MelP5 are unique as neither
      melittin nor other pore-forming peptides release macromolecules significantly
      under the same conditions. MelP5 thus appears to belong to a novel functional
      class of peptide that could form the foundation of multiple potential
      biotechnological applications. 

PMID- 24588402
TI  - Alterations in STriatal-Enriched protein tyrosine Phosphatase expression,
      activation, and downstream signaling in early and late stages of the YAC128
      Huntington's disease mouse model.
AB  - Striatal neurodegeneration and synaptic dysfunction in Huntington's disease are
      mediated by the mutant huntingtin (mHtt) protein. MHtt disrupts calcium
      homeostasis and facilitates excitotoxicity, in part by altering NMDA receptor
      (NMDAR) trafficking and function. Pre-symptomatic (excitotoxin-sensitive)
      transgenic mice expressing full-length human mHtt with 128 polyglutamine repeats
      (YAC128 Huntington's disease mice) show increased calpain activity and
      extrasynaptic NMDAR (Ex-NMDAR) localization and signaling. Furthermore, Ex-NMDAR
      stimulation facilitates excitotoxicity in wild-type cortical neurons via calpain
      mediated cleavage of STriatal-Enriched protein tyrosine Phosphatase 61 (STEP61).
      The cleavage product, STEP33, cannot dephosphorylate p38 mitogen-activated
      protein kinase (MAPK), thereby augmenting apoptotic signaling. Here, we show
      elevated extrasynaptic calpain-mediated cleavage of STEP61 and p38
      phosphorylation, as well as STEP61 inactivation and reduced extracellular signal
      regulated protein kinase 1/2 phosphorylation (ERK1/2) in the striatum of 6-week
      old, excitotoxin-sensitive YAC128 mice. Calpain inhibition reduced basal and NMDA
      induced STEP61 cleavage. However, basal p38 phosphorylation was normalized by a
      peptide disrupting NMDAR-post-synaptic density protein-95 (PSD-95) binding but
      not by calpain inhibition. In 1-year-old excitotoxin-resistant YAC128 mice,
      STEP33 levels were not elevated, but STEP61 inactivation and p38 and ERK 1/2
      phosphorylation levels were increased. These results show that in YAC128 striatal
      tissue, enhanced NMDAR-PSD-95 interactions contributes to elevated p38 signaling
      in early, excitotoxin-sensitive stages, and suggest that STEP61 inactivation
      enhances MAPK signaling at late, excitotoxin-resistant stages. The YAC128
      Huntington's disease mouse model shows early, enhanced susceptibility to NMDA
      receptor-mediated striatal apoptosis, progressing to late-stage excitotoxicity
      resistance. This study shows that elevated NMDA receptor-PSD-95 interactions as
      well as decreased extrasynaptic STriatal-Enriched protein tyrosine Phosphatase 61
      (STEP61) activation may contribute to early enhanced apoptotic signaling. In late
      stage YAC128 mice, reduced STEP61 levels and activity correlate with elevated
      MAPK signaling, consistent with excitotoxicity resistance. Solid and dotted
      arrows indicate conclusions drawn from the current study and other literature,
      respectively. 

PMID- 24588404
TI  - Data mining in psychological treatment research: a primer on classification and
      regression trees.
AB  - Data mining of treatment study results can reveal unforeseen but critical
      insights, such as who receives the most benefit from treatment and under what
      circumstances. The usefulness and legitimacy of exploratory data analysis have
      received relatively little recognition, however, and analytic methods well suited
      to the task are not widely known in psychology. With roots in computer science
      and statistics, statistical learning approaches offer a credible option: These
      methods take a more inductive approach to building a model than is done in
      traditional regression, allowing the data greater role in suggesting the correct
      relationships between variables rather than imposing them a priori.
      Classification and regression trees are presented as a powerful, flexible
      exemplar of statistical learning methods. Trees allow researchers to efficiently
      identify useful predictors of an outcome and discover interactions between
      predictors without the need to anticipate and specify these in advance, making
      them ideal for revealing patterns that inform hypotheses about treatment effects.
      Trees can also provide a predictive model for forecasting outcomes as an aid to
      clinical decision making. This primer describes how tree models are constructed,
      how the results are interpreted and evaluated, and how trees overcome some of the
      complexities of traditional regression. Examples are drawn from randomized
      clinical trial data and highlight some interpretations of particular interest to
      treatment researchers. The limitations of tree models are discussed, and
      suggestions for further reading and choices in software are offered.

PMID- 24588403
TI  - Mediated and moderated effects of neurocognitive impairment on outcomes of
      treatment for substance dependence and major depression.
AB  - OBJECTIVE: Neurocognitive impairment has not consistently predicted substance use
      treatment outcomes but has been linked to proximal mediators of outcome. These
      indirect effects have not been examined in adults with substance dependence and
      co-occurring psychiatric disorders. We examined mediators and moderators of the
      effects of neurocognitive impairment on substance use among adults in treatment
      for alcohol or drug dependence and major depression (MDD). METHOD: Participants
      were veterans (N = 197, mean age = 49.3 years, 90% male, 75% Caucasian) in a
      trial of 2 group interventions for alcohol/drug dependence and MDD. Measures
      examined here included intake neurocognitive assessments and percent days
      drinking (PDD), percent days using drugs (PDDRG), self-efficacy, 12-step
      affiliation, and depressive symptoms measured every 3 months from intake to the
      18-month follow-up. RESULTS: Greater intake neurocognitive impairment predicted
      lower self-efficacy, lower 12-step affiliation, and greater depression severity,
      and these time-varying variables mediated the effects of impairment on future PDD
      and PDDRG. The prospective effects of 12-step affiliation on future PDD were
      greater for those with greater neurocognitive impairment. Impairment also
      interacted with depression to moderate the effects of 12-step affiliation and
      self-efficacy on PDD. Adults with greater impairment and currently severe
      depression had the strongest associations between 12-step affiliation/self
      efficacy and future drinking. CONCLUSIONS: Greater neurocognitive impairment may
      lead to poorer outcomes from group therapy for alcohol/drug dependence and MDD
      due to compromised change in therapeutic processes. Distal factors such as
      neurocognitive impairment can interact with dynamic risk factors to modulate the
      association between therapeutic processes and future drinking outcomes.

PMID- 24588405
TI  - Evaluating therapist adherence in motivational interviewing by comparing
      performance with standardized and real patients.
AB  - OBJECTIVE: The goal of measuring therapist adherence is to determine whether a
      therapist can perform a given treatment. Yet, the evaluation of therapist
      behaviors in most clinical trials is limited. Typically, randomized trials have
      few therapists and minimize therapist variability through training and
      supervision. Furthermore, therapist adherence is confounded with uncontrolled
      differences in patients across therapists. Consequently, the extent to which
      adherence measures capture differences in actual therapist adherence versus other
      sources of variance is unclear. METHOD: We estimated intra-class correlations
      (ICCs) for therapist adherence in sessions with real and standardized patients
      (RPs and SPs), using ratings from a motivational interviewing (MI) dissemination
      trial (Baer et al., 2009) in which 189 therapists recorded 826 sessions with both
      patient types. We also examined the correlations of therapist adherence between
      SP and RP sessions, and the reliability of therapist level adherence scores with
      generalizability coefficients (GCs). RESULTS: ICCs for therapist adherence were
      generally large (average ICC for SPs = .44; average ICC for RPs = .40), meaning
      that a given therapist's adherence scores were quite similar across sessions.
      Both ICCs and GCs were larger for SP sessions compared to RPs on global measures
      of MI adherence, such as Empathy and MI Spirit. Correlations between therapist
      adherence with real and standardized patients were moderate to large on 3 of 5
      adherence measures. CONCLUSION: Differences in therapist-level adherence ratings
      were substantial, and standardized patients have promise as tools to evaluate
      therapist behavior.

PMID- 24588406
TI  - Reaching new heights: comparing interpretation bias modification to exposure
      therapy for extreme height fear.
AB  - OBJECTIVE: Cognitive models of anxiety disorders posit that biases in
      interpretation maintain, and potentially cause, anxiety. This study tested
      whether it is possible to decrease height fear symptoms through cognitive bias
      modification for interpretations (CBM-I). Additionally, the clinical utility of
      CBM-I was tested by comparing it to an already established treatment: exposure
      therapy. METHOD: Extremely height fearful individuals (N = 110) participated in
      the study. Acrophobic symptoms were measured before and after 2 sessions of CBM-I
      and were compared to the standard treatment for acrophobia (exposure therapy), a
      combination of CBM-I and exposure therapy, and a Control condition. RESULTS: In
      line with hypotheses, participants in the 3 active conditions showed greater
      response to treatment than the Control condition in height-relevant
      interpretation bias, symptoms, and behavioral avoidance on a height stressor,
      with few differences between the active conditions. Further, symptom change was
      mediated by change in interpretation bias. CONCLUSIONS: Overall, findings suggest
      that different pathways to fear reduction (exposure vs. shifting interpretations)
      can lead to similar reductions in height fear. This study provides the first
      evidence that directly shifting cognitive processing, even with no therapist
      involvement, can reduce symptoms as effectively as the gold standard, therapist
      directed exposure therapy.

PMID- 24588407
TI  - Multisystemic therapy for high-risk African American adolescents with asthma: a
      randomized clinical trial.
AB  - OBJECTIVE: The primary purpose of the study was to determine whether
      Multisystemic Therapy adapted for health care settings (MST-HC) improved asthma
      management and health outcomes in high-risk African American adolescents with
      asthma. METHOD: Eligibility included self-reported African American ethnicity,
      ages 12 to 16, moderate to severe asthma, and an inpatient hospitalization or at
      least 2 emergency department visits for asthma in the last 12 months. Adolescents
      and their families (N = 170) were randomized to MST-HC or in-home family support.
      Data were collected at baseline and posttreatment (7 months) based on an asthma
      management interview, medication adherence phone diary, and lung function
      biomarker (forced expiratory volume in 1 s [FEV1]). Analyses were conducted using
      linear mixed modeling for continuous outcomes and generalized linear mixed
      modeling for binary outcomes. RESULTS: In intent-to-treat analyses, adolescents
      randomized to MST-HC were more likely to improve on 2 of the measures of
      medication adherence and FEV1. Per-protocol analysis demonstrated that MST-HC had
      a medium effect on adherence measures and had a small to medium effect on lung
      function and the adolescent's response to asthma exacerbations. CONCLUSION: There
      are few interventions that have been shown to successfully improve asthma
      management in minority youth at highest risk for poor morbidity and mortality.
      MST, a home-based psychotherapy originally developed to target behavior problems
      in youth, improved asthma management and lung function compared to a strong
      comparison condition. Further follow-up is necessary to determine whether MST-HC
      reduces health care utilization accounting for seasonal variability. A limitation
      to the study is that a greater number of participants in the control group came
      from single-parent families than in the MST group.

PMID- 24588408
TI  - Feasibility, acceptability, and initial efficacy of an online sexual health
      promotion program for LGBT youth: the Queer Sex Ed intervention.
AB  - Lesbian, gay, bisexual, and transgender (LGBT) youth experience multiple sexual
      health inequities driven, in part, by deficits in parental and peer support,
      school-based sex education programs, and community services. Research suggests
      that the Internet may be an important resource in the development of sexual
      health among LGBT youth. We examined the feasibility of recruiting youth in same
      sex relationships into an online sexual health intervention, evaluated
      intervention acceptability, and obtained initial estimates of intervention
      efficacy. LGBT youth (16 to 20 years old) completed Queer Sex Ed (QSE), an
      online, multimedia sexual health intervention consisting of five modules. The
      final sample (N = 202) completed the pretest, intervention, and posttest
      assessments. The primary study outcomes were sexual orientation identity and self
      acceptance (e.g., coming-out self-efficacy), sexual health knowledge (e.g.,
      sexual functioning), relationship variables (e.g., communication skills), and
      safer sex (e.g., sexual assertiveness). Analyses indicated that 15 of the 17
      outcomes were found to be significant (p < .05). Effect sizes ranged from small
      for sexual orientation (e.g., internalized homophobia) and relationship variables
      (e.g., communication skills) to moderate for safer sex (e.g., contraceptive
      knowledge) outcomes. This study demonstrated the feasibility, acceptability, and
      initial efficacy of QSE, an innovative online comprehensive sexual health program
      for LGBT youth. 

PMID- 24588409
TI  - Hydralazine-induced toxic epidermal necrolysis in a patient on continuous
      ambulatory peritoneal dialysis.
AB  - WHAT IS KNOWN AND OBJECTIVE: Hydralazine is an effective antihypertensive drug
      which acts by vasodilatation. It is well known to cause drug-induced lupus
      erythematosus. Nevertheless, the overall safety profile is good and cutaneous
      adverse effects are uncommon. To the best of our knowledge, hydralazine has never
      been reported to cause Stevens-Johnson syndrome (SJS) or toxic epidermal
      necrolysis (TEN). CASE SUMMARY: We herein report the first case of hydralazine
      induced TEN in a patient with end-staged renal failure. Despite meticulous wound
      management and intensive medical care, the patient died of a sudden cardiac
      arrest on day 10 of admission. WHAT IS NEW AND CONCLUSION: We speculate that
      patients with renal failure may be predisposed to a higher risk of allergy to
      drug entities that are rarely associated. Physicians should be aware that
      hydralazine can be a potential cause for severe allergic reaction such as SJS or
      TEN, particularly in the setting of poor renal excretory function. Patient
      education and cautious monitoring by physicians are essential for early diagnosis
      and hence successful management of the life-threatening condition.

PMID- 24588410
TI  - Atopic dermatitis revisited.

PMID- 24588411
TI  - Clinical characteristics of 15 children with juvenile myelomonocytic leukaemia
      who developed blast crisis: MDS Committee of Japanese Society of Paediatric
      Haematology/Oncology.
AB  - Juvenile myelomonocytic leukaemia (JMML) is a rare haematopoietic stem cell
      disease of early childhood, which can progress to blast crisis in some children.
      A total of 153 children diagnosed with JMML were reported to the Myelodysplastic
      Syndrome Committee in Japan between 1989 and 2007; 15 of them (9.8%) had 20% or
      more blasts in the bone marrow (blast crisis) during the disease course. Blast
      crisis occurred during observation without therapy (n = 3) or with oral 6
      mercaptopurine treatment (n = 9) and in relapse after haematopoietic stem cell
      transplantation (HSCT; n = 3). Six patients had a complex karyotype (5 including
      monosomy 7) and an additional three patients had isolated monosomy 7 at blast
      crisis. Seven patients received HSCT after blast crisis and four of them achieved
      remission. Eleven out of the 15 patients died; the cause of death was disease
      progression in 10 patients and transplant-related complication in one patient. In
      summary, patients with blast crisis have poor prognosis and can be cured only by
      HSCT. The emergence of monosomy 7 and complex karyotype may be characteristic of
      blast crisis in a substantial subset of children. 

PMID- 24588412
TI  - Prevalence and prognostic impact of comorbidity in soft tissue sarcoma: a
      population-based cohort study.
AB  - BACKGROUND: Comorbidity is an important prognostic factor for survival in other
      cancers, but the importance in soft tissue sarcoma has not yet been clarified.
      The aims of this study were to examine the prevalence of comorbidity in soft
      tissue sarcoma patients, and estimate the impact of comorbidity on overall and
      disease-specific mortality. MATERIAL AND METHODS: Overall, 1210 adult patients
      with soft tissue sarcoma in the extremities or trunk wall were identified through
      the Aarhus Sarcoma Registry, a validated population-based database. Information
      on comorbidity was obtained through the National Patient Registry, and a
      Charlson's Comorbidity score was calculated for each patient. The prevalence of
      comorbidity was assessed overall, as well as according to age and year of
      diagnosis. Overall and disease-specific mortality rates according to level of
      comorbidity were computed. The prognostic value of comorbidity was estimated
      using crude and adjusted Cox proportional hazard models. RESULTS: The overall
      prevalence of comorbidity was 25%. The prevalence increased with increasing age,
      and patients with comorbidity had a larger proportion of adverse prognostic
      factors when compared to patients without comorbidity. The five-year disease
      specific mortality was 26% (95% CI 24-29) for patients without comorbidity,
      compared to 33% (95% CI 24-42), 41% (95% CI 32-50), and 44% (95% CI 33-55) for
      patients with mild, moderate, and severe comorbidity, respectively. After
      adjusting for age, sex, stage, tumor size, depth, grade, surgical margin,
      radiotherapy, and chemotherapy, comorbidity was independently associated with an
      increased overall and disease-specific mortality. CONCLUSION: Patients with
      comorbidity had significantly increased overall and disease-specific mortality
      compared to patients without comorbidity, even when adjusting for important
      prognostic factors including age.

PMID- 24588414
TI  - The mystifying nomenclature of cardiac troponin immunoassays.
AB  - The laboratory assessment of cardiospecific troponins(s) represents the
      cornerstone for the diagnosis of acute coronary syndrome (ACS). Although troponin
      immunoassays are classified according to either analytical imprecision or
      percentage of measurable values in a presumably healthy population, it is rather
      clear that the nomenclature of commercial methods according to these systems of
      classification carries several drawbacks. The leading problems in classification
      according to imprecision are represented by the arbitrarity of optimal
      imprecision threshold, the uncertain correspondence between analytical
      performance and clinical outcomes and the improper use of terms, which has also
      been magnified by the lack of specific focus on this topic by regulating bodies
      such as the US Food and Drug Administration (FDA) and the European Union.
      Additional issues emerging from classification according to percentage of
      measurable values include the characterization of healthy population, the
      variation of values according to age, gender and race, as well as the influence
      of comorbidities. Considering that what really matters from a clinical standpoint
      is the clinical performance of the assay rather than the claimed analytical
      characteristics, it seems reasonable at this point in time to introduce a
      paradigm shift and gradually abandon the former analytical classification in
      favour of a different approach, preferable based on clinical outcomes.

PMID- 24588413
TI  - Template matching for auditing hospital cost and quality.
AB  - OBJECTIVE: Develop an improved method for auditing hospital cost and quality.
      DATA SOURCES/SETTING: Medicare claims in general, gynecologic and urologic
      surgery, and orthopedics from Illinois, Texas, and New York between 2004 and
      2006. STUDY DESIGN: A template of 300 representative patients was constructed and
      then used to match 300 patients at hospitals that had a minimum of 500 patients
      over a 3-year study period. DATA COLLECTION/EXTRACTION METHODS: From each of 217
      hospitals we chose 300 patients most resembling the template using multivariate
      matching. PRINCIPAL FINDINGS: The matching algorithm found close matches on
      procedures and patient characteristics, far more balanced than measured
      covariates would be in a randomized clinical trial. These matched samples
      displayed little to no differences across hospitals in common patient
      characteristics yet found large and statistically significant hospital variation
      in mortality, complications, failure-to-rescue, readmissions, length of stay, ICU
      days, cost, and surgical procedure length. Similar patients at different
      hospitals had substantially different outcomes. CONCLUSION: The template-matched
      sample can produce fair, directly standardized audits that evaluate hospitals on
      patients with similar characteristics, thereby making benchmarking more
      believable. Through examining matched samples of individual patients,
      administrators can better detect poor performance at their hospitals and better
      understand why these problems are occurring.

PMID- 24588415
TI  - Veno-venous extracorporeal membrane oxygenation in obese surgical patients with
      hypercapnic lung failure.
AB  - BACKGROUND: In patients with a body mass index (BMI) > 35 kg/m(2) , or in extreme
      cases weighting > 250 kg, we are faced with special challenges in therapy and
      logistics. The aim was to analyze the feasibility of the extracorporeal membrane
      oxygenation (ECMO) in these patients. METHODS: We report 12 adult patients [10
      male, 2 female; mean age 56.7 (34-74) years; mean BMI 47.9 (35-88.6) kg/m(2) ]
      with acute lung failure treated with veno-venous ECMO from 1 January 2009 to 30
      June 2013. All patients were cannulated percutaneously into the right internal
      jugular vein and one of the femoral veins at the bedside. RESULTS: The mean time
      to ECMO after admission to the intensive care unit (ICU) was 2 days (0-10), and
      the mean ECMO run time was 9 days (4 h-20 days). Lung failure occurred in the
      contexts of wound infection (two patients), anaphylactic shock (one patient),
      major trauma (one patients) and pneumonia after surgery (four patients), and
      respiratory failure in abdominal sepsis (four patients). The mean time in the ICU
      was 31 days (0-89), and the mean time at the hospital was 38 days (0-101). Three
      patients died on the system because of multiorgan failure; nine patients were
      weaned from ECMO (75%); and six were patients discharged from the ICU and from
      the hospital (survival rate 50%). CONCLUSIONS: ECMO in obese patients is feasible
      and life saving. Therefore, a percutaneous cannulation remains feasible. The
      goals of the ECMO therapy include early spontaneous breathing, tracheotomy, rapid
      reduction of sedation and adequate analgesia. Rehabilitation includes nutritional
      therapy, as well as psychiatric therapy and bariatric surgery, as perspectives
      for the future.

PMID- 24588416
TI  - Some pregnant women still don't believe drinking is dangerous.

PMID- 24588418
TI  - Outcomes for older trauma patients in the emergency department screening positive
      for alcohol, cocaine, or marijuana use.
AB  - BACKGROUND: Substance use among older adults is an increasing concern, with the
      prevalence of substance use in older populations expected to double in the next
      decade. Drug and alcohol use is associated with trauma risk and outcomes, but
      little is known about the specific risk for older trauma patients. OBJECTIVES: To
      evaluate the association between drug and alcohol use and trauma outcomes among
      adults aged 55 years and older. METHODS: This retrospective observational study
      included older adults from the Illinois Trauma Registry between 1999 and 2009.
      Exclusion criteria were age younger than 55 years or absent date of birth,
      ethanol level, or urine drug screen (UDS). Alcohol intoxication was defined as
      ethanol level greater than 80 mg/dL. UDS was used to screen cocaine and marijuana
      use. Analyses, for both the alcohol and the marijuana/cocaine groups, compared
      outcomes for patients with negative vs. positive screens. RESULTS: 21 320
      patients were included in the alcohol analysis and 17 077 in the drug analysis.
      Compared to non-intoxicated patients, alcohol-intoxicated patients had
      significantly (p < 0.001) lower in-hospital mortality, decreased ICU admission,
      decreased intubation rate, and shorter hospital length of stay. Patients
      screening positive for cocaine or marijuana had significantly longer lengths of
      stay with increased ICU admission compared with those who screened negative.
      CONCLUSION: Among older trauma patients, this study shows significant
      associations with multiple trauma outcomes, including one between elevated
      ethanol concentrations and improved outcomes. Future research into the causes of
      these findings could inform the care of older trauma patients and aid in
      prevention of injuries.

PMID- 24588419
TI  - Alcohol use and alcohol-related consequences: associations with emotion
      regulation difficulties.
AB  - BACKGROUND: Understanding factors associated with alcohol-related consequences is
      an important area of research. Emotional functioning has been associated with
      alcohol-related consequences but there is less research examining a comprehensive
      underlying model of emotional regulation. The Difficulties in Emotion Regulation
      Scale (DERS) is a recent measure developed to assess six facets of emotion
      regulation difficulties that contribute to overall emotional functioning.
      OBJECTIVES: The current study examines associations between these six facets of
      emotion regulation difficulties and problematic alcohol use. METHODS:
      Participants (n = 1758 college students) were recruited as part of a larger study
      and were asked to complete online questionnaires assessing demographics, alcohol
      use and problems, and emotion regulation difficulties. RESULTS: Negative binomial
      hurdle models for alcohol use and alcohol-related consequences were estimated.
      Impulse control difficulties were positively related to the number of drinks
      consumed during the week among active drinkers. Non-acceptance of emotional
      responses, impulse control difficulties, lack of emotional clarity, and
      difficulties engaging in goal-directed behavior were all positively associated
      with number of consequences endorsed. Difficulty engaging in goal-directed
      behavior was also positively associated with the likelihood of experiencing any
      alcohol-related consequences. CONCLUSIONS: The findings support previous research
      indicating that emotion-regulation difficulties are broadly associated with
      alcohol-related consequences. Results suggest exposure and/or mindfulness based
      prevention/interventions with emotion focused psychoeducation may offer one path
      to reducing alcohol-related consequences among college students.

PMID- 24588417
TI  - Beliefs about fetal alcohol spectrum disorder among men and women at alcohol
      serving establishments in South Africa.
AB  - BACKGROUND: South Africa has one of the highest rates of fetal alcohol spectrum
      disorder (FASD) in the world. However, little is known about what men and women
      who attend alcohol serving establishments believe about alcohol use during
      pregnancy and how these beliefs may be related to alcohol use. OBJECTIVES: To
      understand FASD beliefs and related behaviors among men and women attending
      alcohol-serving establishments. METHODS: We surveyed 1047 men (n = 565) and women
      (n = 482) -including pregnant women and men with pregnant partners- attending
      alcohol serving establishments in a township located in Cape Town, South Africa.
      RESULTS: Among both pregnant (n = 53) and non-pregnant (n = 429) women, 54%
      reported drinking alcohol at least 2-4 times per month, and 57% reported having
      at least 3-4 alcohol drinks during a typical drinking session. Pregnant women
      were less likely to believe that they should not drink alcohol and that alcohol
      can harm a fetus when compared to non-pregnant women. Similar findings were
      observed between men with pregnant partners compared to men without pregnant
      partners. Among women, beliefs about how much alcohol pregnant women can safely
      drink were associated with self-reported alcohol use. CONCLUSIONS: Efforts to
      address FASD need to focus on understanding how men and women perceive alcohol
      use during pregnancy and situational factors that contribute to alcohol
      consumption among pregnant women attending alcohol serving establishments.
      Structural and individual-level interventions targeting women at alcohol serving
      establishments should be prioritized to mitigate alcohol use during pregnancy.

PMID- 24588420
TI  - A validation study of the English version of the AlQol 9 to measure quality of
      life.
AB  - BACKGROUND: Quality of life (QoL) is an important clinical and research outcome
      within the drug and alcohol abuse context. The AlQoL 9 is a specific
      questionnaire designed to assess health- and non-health-related consequences of
      alcoholism. The English version of the AlQoL 9 has not been validated using a
      larger sample. OBJECTIVES: The aim of this study was to assess the psychometric
      properties of the English version of AlQoL 9 in a sample of treatment-seeking
      individuals in Australia. METHODS: A sample of 138 participants from inpatient
      and outpatient treatments facilities completed the AlQoL 9 test and the World
      Health Organisation Quality of Life Assessment-BREF (WHOQOL-BREF). The study's
      investigative parameters included the demographic characteristics of the sample,
      internal structure, and convergent validity. Furthermore, correlations between
      the AlQoL 9 scale scores and the scores obtained from the WHOQOL-BREF test were
      investigated using Pearson product-moment correlation analyses. RESULTS: The
      English version of the AlQoL 9 attained a significant Cronbach's alpha of 0.825.
      The mean score obtained in the test was 21.92 (SD = 6.79). Using Varimax
      rotation, the AlQoL 9 yielded one principal factor that had accounted for 37.85%
      of variance. Convergent validity analysis demonstrated significant correlations
      (p < 0.001) between the AlQoL 9 scores and the scores of all four dimensions of
      the WHOQOL-BREF questionnaire. CONCLUSION: The present study demonstrated that
      the English version of the AlQoL 9 constitutes a valid and reliable research
      instrument for evaluating quality of life among alcohol-dependent individuals.

PMID- 24588421
TI  - Memory for drug-related visual stimuli in young adult, cocaine-dependent polydrug
      users.
AB  - BACKGROUND AND OBJECTIVES: Implicit (unconscious) and explicit (conscious) memory
      associations with drugs have been examined primarily using verbal cues. However,
      drug seeking, drug use behaviors, and relapse in chronic cocaine and other drug
      users are frequently triggered by viewing substance-related visual cues in the
      environment. We thus examined implicit and explicit memory for drug picture cues
      to understand the relative extent to which conscious and unconscious memory
      facilitation of visual drug cues occurs during cocaine dependence. METHODS:
      Memory for drug-related and neutral picture cues was assessed in 14 inpatient
      cocaine-dependent polydrug users and a comparison group of 21 young adults with
      limited drug experience (n = 35). Participants completed picture cue exposure,
      free recall and recognition tasks to assess explicit memory, and a repetition
      priming task to assess implicit memory. RESULTS: Drug cues, compared to neutral
      cues, were better explicitly recalled and implicitly primed, and especially so in
      the cocaine group. In contrast, neutral cues were better explicitly recognized,
      and especially in the control group. CONCLUSION: Certain forms of explicit and
      implicit memory for drug cues were enhanced in cocaine users compared to controls
      when memory was tested a short time following cue exposure. Enhanced unconscious
      memory processing of drug cues in chronic cocaine users may be a behavioral
      manifestation of heightened drug cue salience that supports drug seeking and
      taking. There may be value in expanding intervention techniques to utilize
      cocaine users' implicit memory system.

PMID- 24588424
TI  - C-H activation of methyl arenes in the MnO2-mediated aroylation of N
      chlorosulfoximines.
AB  - An investigation into the reactivity profile of N-halogenated sulfoximines has
      led to the development of a new method for the synthesis of N-aroylated
      sulfoximines. This protocol involves the manganese oxide promoted C-H activation
      of methyl arenes to form an aroyl intermediate which then reacts readily with N
      chlorosulfoximines to form a series of valuable aroyl sulfoximine derivatives in
      high yields. 

PMID- 24588423
TI  - Susceptibility of Stenotrophomonas maltophilia clinical strains in China to
      antimicrobial combinations.
AB  - We aimed to investigate the activity levels of several combinations of
      antimicrobials against Stenotrophomonas maltophilia. In this study, the
      antimicrobial susceptibility of S. maltophilia clinical isolates was determined,
      and the synergistic activity of three pairs of antimicrobial combinations was
      evaluated by the fractional inhibitory concentration index (FICI). The
      antimicrobial susceptibility in vitro against 83 S. maltophilia strains was
      greater for minocycline (80.7%) than for trimethoprim-sulfamethoxazole (51.8%),
      and levofloxacin (50.6%). The rate of resistance was highest for ticarcillin
      clavulanate and ceftazidime (63.8%) and resistance to trimethoprim
      sulfamethoxazole (TMP-SMX) was 48.2%. All three combinations were tested against
      susceptible isolates. Two of the combinations, TMP-SMX+ceftazidime and
      levofloxacin+ceftazidime were more effective than the combination of TMP
      SMX+levofloxacin. We recommend acquiring more clinical data in order to explore
      combination therapy, which is a promising treatment of S. maltophilia infections.

PMID- 24588425
TI  - Editors' report, November 2013.

PMID- 24588426
TI  - Colesevelam for Type 2 diabetes mellitus: an abridged Cochrane review.

PMID- 24588428
TI  - Acylammonium salts as dienophiles in Diels-Alder/lactonization organocascades.
AB  - alpha,beta-Unsaturated acylammonium salts, generated in situ from commodity acid
      chlorides and a chiral isothiourea organocatalyst, comprise a new and versatile
      family of chiral dienophiles for the venerable Diels-Alder (DA) cycloaddition.
      Their reactivity is unveiled through a highly diastereo- and enantioselective
      Diels-Alder/lactonization organocascade that generates cis- and trans-fused
      bicyclic gamma- and delta-lactones bearing up to four contiguous stereocenters.
      Moreover, the first examples of DA-initiated, stereodivergent organocascades are
      described delivering complex scaffolds found in bioactive compounds. The origins
      of stereoselectivity are rationalized through computational studies. In addition,
      the utility of this methodology is demonstrated through a concise approach to the
      core structure of glaciolide and formal syntheses of fraxinellone, trisporic
      acids, and trisporols. 

PMID- 24588429
TI  - The Australian and New Zealand Risk of Death (ANZROD) model: getting mortality
      prediction right for intensive care units.

PMID- 24588427
TI  - Inhibition of striatal-enriched tyrosine phosphatase 61 in the dorsomedial
      striatum is sufficient to increased ethanol consumption.
AB  - The STriatal-Enriched protein tyrosine Phosphatase 61 (STEP61 ) inhibits the
      activity of the tyrosine kinase Fyn and dephosphorylates the GluN2B subunit of
      the NMDA receptor, whereas the protein kinase A phosphorylation of STEP61
      inhibits the activity of the phosphatase (Pharmacol. Rev., 64, , p. 65).
      Previously, we found that ethanol activates Fyn in the dorsomedial striatum (DMS)
      leading to GluN2B phosphorylation, which, in turn, underlies the development of
      ethanol intake (J. Neurosci., 30, , p. 10187). Here, we tested the hypothesis
      that inhibition of STEP61 by ethanol is upstream of Fyn/GluN2B. We show that
      exposure of mice to ethanol increased STEP61 phosphorylation in the DMS, which
      was maintained after withdrawal and was not observed in other striatal regions.
      Specific knockdown of STEP61 in the DMS of mice enhanced ethanol-mediated Fyn
      activation and GluN2B phosphorylation, and increased ethanol intake without
      altering the level of water, saccharine, quinine consumption or spontaneous
      locomotor activity. Together, our data suggest that blockade of STEP61 activity
      in response to ethanol is sufficient for the activation of the Fyn/GluN2B pathway
      in the DMS. Being upstream of Fyn and GluN2B, inactive STEP61 in the DMS primes
      the induction of ethanol intake. We show that ethanol-mediated inhibition of
      STEP61 in the DMS leads to Fyn activation and GluN2B phosphorylation. (a) Under
      basal conditions, active STEP61 inhibits Fyn activity and dephosphorylates
      GluN2B. (b) Ethanol leads to the phosphorylation of STEP61 on a specific
      inhibitory site. The inhibition of STEP61 activity contributes to the activation
      of Fyn in response to ethanol, which, in turn, phosphorylates GluN2B. These
      molecular adaptations in the DMS promote ethanol drinking. 

PMID- 24588430
TI  - High-stakes assessment of the non-technical skills of critical care trainees
      using simulation: feasibility, acceptability and reliability.
AB  - OBJECTIVE: To evaluate the use of high-fidelity simulation for summative high
      stakes assessment of intensive care trainees, focusing on non-technical skills
      (NTS), testing feasibility and acceptability of simulation assessment, and the
      reliability of two NTS rating scales. DESIGN, SETTING AND PARTICIPANTS:
      Prospective observational study of senior intensive care trainees in a simulated
      specialist examination. METHODS: Participants undertook a simulated patient
      management scenario and were assessed using two rating scales: the Anaesthesia
      Non-technical Skills (ANTS) scale and the Ottawa Global Rating Scale (GRS).
      Assessors were trained, currently active, high-stakes examiners. Participants
      also completed a survey on simulation-based summative assessment. OUTCOME
      MEASURES: The inter-rater reliability of two rating scales for NTS assessment. We
      evaluated the feasibility of simulation-based assessment, and used survey results
      to assess acceptability to participants. RESULTS: Simulation assessment was
      feasible. Participants considered simulation-based high-stakes assessment to be
      acceptable and felt their scenario performance was reflective of real-world
      performance. Participants identified a need for debriefing following scenario
      based assessment. Inter-rater reliability was fair for the ANTS and Ottawa GRS
      scores (intra-class correlation coefficient, 0.39 and 0.42, respectively). There
      was only fair agreement between raters for an NTS pass or fail (weighted kappa,
      0.32) and for a technical skills pass or fail (weighted kappa, 0.36).
      CONCLUSIONS: Summative high-stakes assessment using a single simulated scenario
      was feasible and acceptable to senior intensive care trainees. The low inter
      rater reliability for the ANTS and Ottawa GRS rating scales and for pass or fail
      discrimination may limit its incorporation into an existing examination format.

PMID- 24588431
TI  - Glycaemic variability, infections and mortality in a medical-surgical intensive
      care unit.
AB  - OBJECTIVE: In critically ill patients, glycaemic variability (GV) was reported as
      a better predictor of mortality than mean blood glucose level (BGL). We compared
      the ability of different GV indices and mean BGLs to predict mortality and
      intensive care unit-acquired infections in a population of ICU patients. DESIGN,
      SETTING AND PARTICIPANTS: Retrospective study on adult ICU patients with >= three
      BGL measurements. GV was assessed by SD, coefficient of variation (CV) and mean
      amplitude of glycaemic excursion (MAGE), and by one timeweighted index, the
      glycaemic lability index (GLI), and compared with mean BGL. We studied 2782
      patients admitted to the 12-bed medical-surgical ICU of a teaching hospital from
      January 2004 until December 2010. MAIN OUTCOME MEASURES: Logistic regression
      analyses were performed to assess the association between GV and ICU mortality
      and ICU-acquired infections. The areas under receiver operating characteristic
      curves were calculated to compare the discriminatory ability of GV and mean BGL
      for infections and mortality. RESULTS: Mortality was 16.6%, and 30% of patients
      had at least one infection. Patients with infections or diabetes or who were
      treated with insulin had a higher mean BGL and GV than other patients. GLI, SD,
      CV and MAGE were significantly associated with infections and mortality; mean BGL
      was not. Quartiles of increasing GLI were independently associated with higher
      mortality and an increased infection rate. Patients in the upper quartile of mean
      BGL and GLI had the strongest association with infections (odds ratio, 5.044 [95%
      CI, 1.695-15.007]; P = 0.004). CONCLUSION: High GV is associated with higher risk
      of ICUCrit acquired infection and mortality.

PMID- 24588432
TI  - A brief review of recent trends in Victorian intensive care, 2000-2011.
AB  - BACKGROUND: Review of resource use and patient outcomes of intensive care unit
      services over time provides insights into service delivery and safety. OBJECTIVE:
      To examine temporal trends in resource consumption and risk-adjusted mortality of
      adult ICU patients in Victoria. DESIGN, PARTICIPANTS AND SETTING: Retrospective
      cohort study of 214 619 adult ICU admissions recorded from 23 major hospitals
      over 12 years from 1 July 1999 to 30 June 2011. OUTCOMES: Primary outcomes were
      population rates of ICU admission and mechanical ventilation (MV), ICU and
      hospital length of stay, and hospital survival. Secondary outcomes included
      average ICU and MV bed numbers. Administrative data were derived from the
      Victorian Admitted Episodes Dataset and the Australian Bureau of Statistics. The
      Critical Care Outcome Prediction Equation informed estimates for risk-adjusted
      mortality. Temporal mortality trends were evaluated for outcome estimates and
      hierarchical logisticregression trends were evaluated for risk-adjusted
      mortality. RESULTS: Of ICU admissions, 104 103 (48.5%) were patients who received
      MV, and 87.6% ICU admissions were adults who survived to hospital discharge.
      There was a decline in the risk-adjusted mortality (odds ratio, 0.967 per year;
      95% CI, 0.963-0.971; P<0.001). Similar results were found in 17 hospitals (74%)
      and in nine of 10 major diagnostic subgroups. There was an increase of 5.2
      occupied ICU beds per year (range, ?4.2 ICU beds per year; P=0.002). Despite ICU
      admissions being a minority cohort (2.5% of public hospital admissions) this
      group used 8.6% of hospital bed-days and attracted 19.5% of funding. CONCLUSIONS:
      There was an increase in ICU resource availability and evidence of improvement in
      hospital survival, suggesting improved quality of care. These evaluation methods
      may be useful in monitoring statewide capacity, service delivery and patient
      safety.

PMID- 24588433
TI  - Systemic and renal haemodynamic effects of fluid bolus therapy: sodium chloride
      versus sodium octanoate-balanced solution.
AB  - BACKGROUND: Solutions with high chloride concentrations, like normal saline (NS),
      may adversely affect renal blood flow (RBF). We compared the systemic and renal
      haemodynamic effects of a bolus of NS with those of a novel isotonic solution
      containing a physiological concentration of chloride and sodium octanoate (SOct)
      in healthy conscious sheep. METHODS: We performed an experimental double-blind
      cross-over animal study. After chronic pulmonary and renal artery flow probe
      insertion, animals were randomly assigned to receive rapid intravenous infusion
      (1 L over 30 minutes) of either NS or SOct. Haemodynamic parameters were recorded
      continuously before and after treatment. RESULTS: NS and SOct had similar
      dilutional effects on the haematocrit. Both induced a short-lived increase in
      cardiac output (CO) and total peripheral conductance which dissipated by 60
      minutes. However, SOct increased RBF more than NS (peak values, 213.4+/
      34.3mL/min v 179.3+/-35.6mL/min; P < 0.001) with a greater RBF/CO ratio (peak
      values, 12.2%+/-3.7% v 10.6%+/-3.6%; P < 0.001). CONCLUSIONS: NS and SOct appear
      to have similar systemic haemodynamic effects. However, OS significantly
      increases RBF compared with normal saline.

PMID- 24588434
TI  - The relationship between hypophosphataemia and outcomes during low-intensity and
      high-intensity continuous renal replacement therapy.
AB  - AIM: To identify risk factors for development of hypophosphataemia in patients
      treated with two different intensities of continuous renal replacement therapy
      (CRRT) and to assess the independent association of hypophosphataemia with major
      clinical outcomes. MATERIALS AND METHODS: We performed secondary analysis of data
      collected from 1441 patients during a large, multicentre randomised controlled
      trial of CRRT intensity. We allocated patients to two different intensities of
      CRRT (25mL/kg/hour vs 40 mL/kg/hour of effluent generation) and obtained daily
      measurement of serum phosphate levels. RESULTS: We obtained 14 115 phosphate
      measurements and identified 462 patients (32.1%) with hypophosphataemia, with
      peak incidence on Day 2 and Day 3. With lower intensity CRRT, there were 58
      episodes of hypophosphataemia/1000 patient days, compared with 112 episodes/1000
      patient days with higher intensity CRRT (P < 0.001). On multivariable logistic
      regression analysis, higher intensity CRRT, female sex, higher Acute Physiology
      and Chronic Health Evaluation score and hypokalaemia were independently
      associated with an increased odds ratio (OR) for hypophosphataemia. On
      multivariable models, hypophosphataemia was associated with better clinical
      outcomes, but when analysis was confined to patients alive at 96 hours,
      hypophosphataemia was not independently associated with clinical outcomes.
      CONCLUSIONS: Hypophosphataemia is common during CRRT and its incidence increases
      with greater CRRT intensity. Hypophosphataemia is not a robust independent
      predictor of mortality. Its greater incidence in the higher intensity CRRT arm of
      the Randomised Evaluation of Normal vs Augmented Level trial does not explain the
      lack of improved outcomes with such treatment.

PMID- 24588435
TI  - Measuring visceral fat, subcutaneous fat and skeletal muscle area changes by
      computed tomography in acute pancreatitis: a retrospective, single-centre study.
AB  - OBJECTIVE: To show that body composition of intensive care unit patients can be
      analysed with existing computed tomography (CT) images. We planned to describe
      changes in visceral fat area (VFA), subcutaneous fat area (SFA) and muscle area
      (MA) on analysis of specific CT images during acute pancreatitis requiring an ICU
      admission. DESIGN, SETTING AND PARTICIPANTS: Retrospective analysis of body
      composition using existing CT images, in an ICU of a tertiary university
      affiliated hospital 2005-2010, examining 21 patients with acute pancreatitis and
      CT imaging on two separate occasions within their hospital admission. MAIN
      OUTCOME MEASURES: VFA, SFA, VFA:SFA ratio and MA. Medical records were hand
      searched to identify ICU and hospital mortalities and other clinical outcomes.
      RESULTS: Three women and 18 men had 84 CT scans analysed, from the level of the
      right renal hilum and L3 vertebra. The median patient age was 52 years. The
      median time between CT scans was 9.4 days and the mean Acute Physiology and
      Chronic Health Evaluation II score was 20.2. ICU mortality was 9%. Analysis
      showed a decrease in VFA from a median of 229.2 cm2 to 202.1 cm2 (P < 0.01) and a
      decrease in VFA:SFA ratio from a median of 1.20 to 1.05 (P < 0.01) during the
      acute illness. MA did not change significantly. CONCLUSIONS: The body composition
      of ICU patients can be analysed through existing CT images. Pancreatitis
      requiring ICU admission causes a 12% decrease in VFA.

PMID- 24588436
TI  - Improved consistency in interpretation and management of cardiovascular variables
      by intensive care staff using a computerised decision-support system.
AB  - OBJECTIVE: To investigate the potential of a computerised decision-support system
      (CDSS) to improve consistency of haemodynamic evaluation and treatment
      suggestions by intensive care unit clinical staff with different levels of
      expertise and experience. DESIGN, SETTING AND PARTICIPANTS: Prospective
      observational study in a tertiary general ICU, of 20 patients admitted after
      elective cardiac surgery and assessed by staff specialists, senior registrars,
      registrars and nurses. MAIN OUTCOME MEASURES: A CDSS was used to display key
      cardiovascular variables, including mean systemic filling pressure analogue
      (Pmsa), heart efficiency (Eh) and vascular resistance (SVR). Staff were asked to
      score Pmsa, Eh and SVR ranging from -5 (grossly subnormal) through 0 (normal) to
      5 (grossly supranormal), first without and then with access to the CDSS.
      Recommendations for therapeutic interventions were recorded. Maximal differences
      (diffmax) and the proportion of minimal disagreement (diffmin) between staff were
      evaluated. RESULTS: Without use of the CDSS, Pmsa was commonly underestimated, Eh
      was overestimated, and there was no clear trend for SVR, compared with
      estimations using the CDSS. Diffmax was reduced and diffmin was increased after
      access to the CDSS. Agreement between all categories of staff on therapeutic
      interventions increased from four to 18 patients after access to the CDSS.
      CONCLUSION: Use of a CDSS significantly improved the consistency between
      categories of clinical ICU staff in assessing the cardiovascular status and
      making management decisions in postoperative cardiac surgery patients.

PMID- 24588438
TI  - Medical emergency teams and end-of-life care: a systematic review.
AB  - BACKGROUND: The medical emergency team (MET) is now common in many hospitals.
      Apart from early identification and management of patients who are potentially
      unwell on the ward, the MET may also be involved in end-of-life (EOL) care. It is
      not known how often METs perform EOL interventions. METHODS: We performed a
      systematic review to identify the frequency of EOL interventions in comparison
      with other commonly performed interventions during MET calls. We searched PubMed,
      Embase and bibliographies of retrieved articles. Studies which reported METs that
      delivered EOL care were included. We assessed the validity of all included
      studies. RESULTS: Thirty-five studies met our inclusion criteria. We assessed the
      frequency of MET interventions and EOL care in 16 studies. Limitations of Medical
      Therapy (LOMT) were instituted in 1.7% to 30.8% of MET calls. Discussions
      regarding LOMT were frequently performed more commonly than resuscitation
      interventions such as endotracheal intubation. None of the included studies
      reported palliative care interventions after MET calls. CONCLUSIONS: We show that
      EOL care is commonly delivered during MET calls, and should be emphasised in
      training for MET members.

PMID- 24588437
TI  - Continuous intra-arterial blood glucose monitoring using quenched fluorescence
      sensing: a product development study.
AB  - BACKGROUND: Continuous glucose monitoring (CGM) has the potential to improve the
      management of blood glucose (BG) and so improve patient safety and outcomes in
      intensive care units. The GluCath Intravascular CGM (IV-CGM) System (GluMetrics)
      uses a novel quenched chemical fluorescence sensing mechanism to measure BG.
      OBJECTIVE: We aimed to assess the safety and performance of the GluCath IV-CGM
      for a 24-hour period in 20 patients admitted to an ICU after cardiac surgery.
      METHODS: Heparin-bonded sensors were deployed via a standard 20-gauge radial
      arterial catheter inserted for routine care in 21 participants after cardiac
      surgery. Sensors were inserted shortly after ICU admission and BG was monitored
      for up to 24 hours. After an in vivo calibration, the system recorded BG every
      minute. Ultrasound examinations checked for sensor position and the presence of
      thrombus. Outcome measures were qualitative (ease of use, interference with
      clinical care, blood pressure monitoring and blood sampling) and quantitative
      (accuracy in comparison with hourly measurements from a reference analyser). BG
      was managed according to usual protocols. RESULTS: Of 21 sensors deployed, one
      failed and one was malpositioned due to operator error. A total of 488 reference
      samples were collected, with BG concentrations ranging from 4.7mmol/L to 13.4
      mmol/L. Calibration samples, samples from the malpositioned sensor and six
      samples affected by technical errors were excluded. Of 437 paired sensor and
      reference measurements used to assess accuracy, 353 (80.8%) met International
      Organization for Standardization standard 15197: 2003 criteria (within 20% of
      reference when BG>=4.2mmol/L). The aggregate mean absolute relative difference
      (MARD) was 13.0%, with the MARD for individual sensors ranging from 4.7% to
      33.5%. Preremoval ultrasounds detected clinically insignificant intravascular
      thrombus in five of 21 patients (23.8%). No sensor interfered with clinical care,
      haemodynamic monitoring or blood sampling. There were no device related serious
      adverse events. CONCLUSIONS: In this product development study, use of the
      GluCath system for 24 hours after cardiac surgery had no adverse effect on
      haemodynamic monitoring, arterial blood sampling or clinical care. Overall
      accuracy was acceptable in the context of the first phase of a product
      development study.

PMID- 24588439
TI  - Prolonged venovenous extracorporeal membrane oxygenation without anticoagulation:
      a case of Goodpasture syndrome-related pulmonary haemorrhage.
AB  - We present a 16-year-old male with severe acute respiratory and renal failure as
      a result of Goodpasture syndrome, requiring venovenous extracorporeal membrane
      oxygenation (VV-ECMO) for pulmonary haemorrhage. The patient received no systemic
      anticoagulation for 25 of 26 ECMO days (20 days consecutively) and suffered no
      coagulation-related adverse events. The patient had a subtherapeutic
      anticoagulation profile according to recommended ECMO guidelines during most of
      this time. The patient made a full recovery without respiratory compromise, ECMO
      circuit failure, thrombotic events or the need for ongoing haemodialysis. 

PMID- 24588440
TI  - Invasive blood pressure recording comparing nursing charts with an electronic
      monitor: a technical report.
AB  - BACKGROUND: Blood pressure management (assessed using nursing charts) in the
      early phase of septic shock may have an effect on renal outcomes. Assessment of
      mean arterial pressure (MAP) values as recorded on nursing charts may be
      inaccurate. AIM: To determine the difference between hourly blood pressure values
      as recorded on the nursing charts and hourly average blood pressure values over
      the corresponding period obtained electronically from the bedside monitor.
      METHODS: We studied 20 patients with shock requiring vasopressor support and
      invasive blood pressure monitoring. Hourly blood pressure measurements were
      recorded on the nursing charts over a 12-hour period. Blood pressure values
      recorded every 10 minutes were downloaded from electronic patient monitors over
      the corresponding period. The hourly average of the 10-minute blood pressure
      values was compared with the measurements recorded on the nursing charts.
      RESULTS: We assessed 240 chart readings and 1440 electronic recordings. Average
      chart MAP was 72.54 mmHg and average electronic monitor MAP was 71.54 mmHg. MAP
      data from the two sources showed a strong correlation (rho0.71, P < 0.005). Bland
      Altman assessment revealed acceptable agreement, with a mean bias of 1mmHg and
      95% limits of agreement of -11.76 mmHg and 13.76 mmHg. Using average data over 6
      hours, 95% limits of agreement narrowed to -6.79mmHg and 8.79mmHg. CONCLUSION:
      With multiple measurements over time, mean blood pressure as recorded on nursing
      charts reasonably approximates mean blood pressure recorded on the monitor.

PMID- 24588441
TI  - Critical care statistical analysis plans.

PMID- 24588442
TI  - Critical care statistical analysis plans. In reply.

PMID- 24588443
TI  - Critical care statistical analysis plans. In reply.

PMID- 24588444
TI  - Identification of antihyperuricemic peptides in the proteolytic digest of shark
      cartilage water extract using in vivo activity-guided fractionation.
AB  - A peptide that exerts antihyperuricemic activity after oral administration was
      identified from a microbial protease (alcalase) digest of the water extract of
      shark cartilage by in vivo activity-guided fractionation, using oxonate-induced
      hyperuricemic rats. Water extract of shark cartilage was first fractionated by
      preparative ampholine-free isoelectric focusing, followed by preparative reversed
      phase liquid chromatography. The antihyperuricemic activity of the alcalse
      digests of the obtained fractions was evaluated using an animal model. Alcalase
      digests of the basic and hydrophobic fractions exerted antihyperuricemic
      activity. A total of 18 peptides were identified in the alcalase digest of the
      final active fraction. These peptides were chemically synthesized and evaluated
      for antihyperuricemic activity. Tyr-Leu-Asp-Asn-Tyr and Ser-Pro-Pro-Tyr-Trp-Pro
      Tyr lowered the serum uric acid level via intravenous injection at 5 mg/kg of
      body weight. Furthermore, orally administered Tyr-Leu-Asp-Asn-Tyr showed
      antihyperuricemic activity. Therefore, these peptides are at least partially
      responsible for the antihyperuricemic activity of the alcalase digest of shark
      cartilage.

PMID- 24588445
TI  - Gender similarities and differences in sexual arousal, desire, and orgasmic
      pleasure in the laboratory.
AB  - Relatively little is known about gender differences in the orgasm experience. The
      objectives of this study were to compare men's and women's patterns of sexual
      arousal and desire before and after orgasm, and the predictors of their orgasmic
      pleasure. Using their typical technique, where masturbation enjoyment was similar
      to that experienced at home, 38 men and 38 women masturbated to orgasm in the
      laboratory. Physiological sexual arousal (genital temperature) and subjective
      sexual arousal and desire measurements were taken at baseline, after masturbation
      almost to orgasm, and immediately and 15 minutes after orgasm. In both genders,
      all measures increased significantly during masturbation, with a greater buildup
      leading to a more pleasurable orgasm. After orgasm, however, sexual arousal and
      desire decreased more quickly and consistently in men than in women, thereby
      replicating Masters and Johnson's (1966) observations. More men than women
      exhibited resolution of subjective sexual arousal and sexual satiation; their
      genital temperature also decreased more than women's but did not return to
      baseline. Women's orgasmic pleasure was related to a postorgasmic decrease in
      genital temperature but, unexpectedly, the maintenance of subjective sexual
      arousal and desire. Future studies should explore whether this pattern explains
      gender differences in the pursuit of additional orgasms.

PMID- 24588446
TI  - Authors' reply.

PMID- 24588447
TI  - Farewell to Drs. Ivan Diamond and T.-K. Li.

PMID- 24588448
TI  - Cytochrome P450 pharmacogenetics in African populations: implications for public
      health.
AB  - INTRODUCTION: Africa harbors a disproportionate burden of disease when taking
      into account the triple challenge caused by HIV/AIDS, tuberculosis (TB) and
      malaria, against a backdrop of an increasing burden of noncommunicable diseases.
      More than 80% of therapeutic drugs used in the management of these
      diseases/conditions are metabolized by CYP enzymes that exhibit genetic
      polymorphisms. AREAS COVERED: There is variability in the expression and
      activities of CYPs resulting in interindividual differences in the response to
      standard doses of therapeutic drugs, due to genetic polymorphisms, which exhibit
      both quantitative and qualitative differences between racial and between ethnic
      groups. The review aims to evaluate the implications of the genetic variation in
      CYPs on the public health of Africans. The CYPs reviewed here metabolize most of
      the commonly used therapeutic drugs and include CYP1A2, 2A6, 2B6, 2C8, 2C9, 2C19,
      2D6, 3A4 and 3A5. Allele frequencies are compared between African ethnic groups
      and among populations of African, Asian and European origin. Data are obtained
      from our own studies and literature. EXPERT OPINION: The variability in the
      pattern of genetic variation between populations translates into differences in
      drug response. Understanding CYP variability improves rational drug use and has
      public health significance.

PMID- 24588449
TI  - 2014 International Bioethics Forum between UK and China and the professional
      development of bioethics in China.

PMID- 24588450
TI  - Investigation of the aggregation process of amyloid-beta-(16-22) peptides and the
      dissolution of intermediate aggregates.
AB  - The aggregation processes of amyloid-beta-(16-22) peptides (Abeta16-22) are
      investigated by atomic force microscopy (AFM). It is found that Abeta16-22
      peptides quickly aggregate from monomers to oligomers and flakelike structures
      and finally to fibrils. In particular, unusual morphology change is observed in
      an early stage of aggregation; that is, the originally formed flakelike
      structures would disappear in the following aggregation processes. To determine
      the evolution of the flakelike structures, in situ AFM imaging is carried out in
      liquid to reveal the real-time morphology change of Abeta16-22. The results
      provide clear evidence that the flakelike structures are in an unstable
      intermediate state, which would be dissolved into oligomers or short protofibrils
      for reorganization. Further fluorescence and attenuated total reflectance Fourier
      transform infrared (ATR-FTIR) experiments on thioflavin T(ThT) suggest that those
      flakelike structures contain beta-sheet components. 

PMID- 24588451
TI  - Phototherapy for vulvar lichen simplex chronicus: an 'off-label use' of a comb
      light device.

PMID- 24588453
TI  - The current practices of speech-language pathologists in providing information to
      clients with traumatic brain injury.
AB  - The provision of information about cognitive-communication disorders (CCDs)
      following traumatic brain injury (TBI) is important given the impact these
      communication impairments can have on the rehabilitation of people with TBI. This
      study describes the results of an online survey which investigated the current
      practices of 74 Australian speech-language pathologists (SLPs) working with
      adults with TBI. Thirty-seven SLPs outlined their practices in information
      provision. SLPs reported they provide information to adults with TBI about CCDs,
      the impact of CCDs on participation in life activities, and rehabilitation from
      CCDs. In addition, SLPs identified barriers and facilitators to information
      provision. Barriers identified included time, impairments resulting from TBI, and
      personal characteristics of the client. Facilitators included family functioning
      and support and the multidisciplinary team. Findings of this research indicate a
      need for some changes in the format and content of information that SLPs provide
      to adults with TBI, to ensure they can achieve fundamental levels of health
      literacy and better health outcomes.

PMID- 24588452
TI  - Intranasal delivery of central nervous system-retargeted human mesenchymal
      stromal cells prolongs treatment efficacy of experimental autoimmune
      encephalomyelitis.
AB  - Treatment with mesenchymal stromal cells (MSCs) is currently of interest for a
      number of diseases including multiple sclerosis. MSCs are known to target
      inflamed tissues, but in a therapeutic setting their systemic administration will
      lead to few cells reaching the brain. We hypothesized that MSCs may target the
      brain upon intranasal administration and persist in central nervous system (CNS)
      tissue if expressing a CNS-targeting receptor. To demonstrate proof of concept,
      MSCs were genetically engineered to express a myelin oligodendrocyte glycoprotein
      specific receptor. Engineered MSCs retained their immunosuppressive capacity,
      infiltrated into the brain upon intranasal cell administration, and were able to
      significantly reduce disease symptoms of experimental autoimmune
      encephalomyelitis (EAE). Mice treated with CNS-targeting MSCs were resistant to
      further EAE induction whereas non-targeted MSCs did not give such persistent
      effects. Histological analysis revealed increased brain restoration in engineered
      MSC-treated mice. In conclusion, MSCs can be genetically engineered to target the
      brain and prolong therapeutic efficacy in an EAE model. 

PMID- 24588454
TI  - Exploration of the structural and convergent validity of the Social Problem
      Solving Inventory-Revised with Native American youth.
AB  - The structural invariance and concurrent validity of the Social Problem-Solving
      Inventory-Revised (SPSI-R) (D'Zurilla, Nezu, & Maydeu-Olivares, 2002) were
      explored with a sample of 699 rural Native American youth (mean age 15.9 years;
      51.7% female) from the south central United States. Using confirmatory factor
      analysis, it was concluded that the structural integrity of the SPSI-R was
      largely upheld; however, differences with prior research emerged in response to
      one item, which may reflect cultural influences. Construct validity of the SPSI-R
      scales was supported through correlations with the Hope Scale (Snyder, Harris,
      Anderson, Holleran, Irving, Sigmon,... Harney, 1991) in directions consistent
      with problem-solving theory and prior empirical research. Relationships between
      SPSI-R scales and acculturation also were examined. Implications are discussed
      regarding further research on social problem solving with diverse cultural
      groups.

PMID- 24588455
TI  - Cultural adaptation and health literacy refinement of a brief depression
      intervention for Latinos in a low-resource setting.
AB  - Few studies addressing the mental health needs of Latinos describe how
      interventions are tailored or culturally adapted to address the needs of their
      target population. Without reference to this process, efforts to replicate
      results and provide working models of the adaptation process for other
      researchers are thwarted. The purpose of this article is to describe the process
      of a cultural adaptation that included accommodations for health literacy of a
      brief telephone cognitive-behavioral depression intervention for Latinos in low
      resource settings. We followed a five-stage approach (i.e., information
      gathering, preliminary adaptation, preliminary testing, adaptation, and
      refinement) as described by Barrera, Castro, Strycker, and Toobert (2013) to
      structure our process. Cultural adaptations included condensation of the
      sessions, review, and modifications of materials presented to participants
      including the addition of visual aids, culturally relevant metaphors, values, and
      proverbs. Feedback from key stakeholders, including clinician and study
      participants, was fundamental to the adaptation process. Areas for further
      inquiry and adaptation identified in our process include revisions to the
      presentation of "cognitive restructuring" to participants and the inclusion of
      participant beliefs about the cause of their depression. Cultural adaptation is a
      dynamic process, requiring numerous refinements to ensure that an intervention is
      tailored and relevant to the target population.

PMID- 24588456
TI  - Ultrasonography-guided radial artery catheterization is superior compared with
      the traditional palpation technique: a prospective, randomized, blinded,
      crossover study.
AB  - BACKGROUND: Radial artery catheterization is gaining popularity for diagnostic
      and interventional procedures. Palpation technique is widely used for the
      procedure, but ultrasonography has been shown to increase catheterization
      success. A recently described ultrasonography technique is termed 'dynamic needle
      tip positioning'. We aimed to compare the traditional palpation technique and
      dynamic needle tip positioning technique in regard to clinically relevant end
      points. METHODS: The study was conducted as a randomized, patient-blinded,
      crossover study. Patients underwent bilateral radial artery catheterization using
      both techniques. The primary end point of the study was needle manipulation time.
      Additional end points were (1) the number of skin perforations, (2) the number of
      attempts targeting the vessel, (3) the number of catheters placed in first
      attempt and (4) the number of catheters used. RESULTS: Forty patients were
      analyzed. There was no significant difference in median needle manipulation time
      [32 s (range 11-96 s) vs. 39 s (range 9-575 s), P = 0.525], although the variance
      was lower in the dynamic needle tip positioning group (P < 0.001). In the
      traditional palpation technique group, a higher number of skin perforations (57
      vs. 40, P = 0.003), catheters (46 vs. 40, P = 0.025) and attempts targeting the
      vessel (104 vs. 43, P < 0.001) were necessary compared with the ultrasonography
      dynamic needle tip positioning group. First attempt success rate was
      significantly higher in the ultrasonography dynamic needle tip positioning group
      (23/40 vs. 38/40, P < 0.001). CONCLUSION: Ultrasonography guidance using the
      dynamic needle tip positioning technique for radial artery catheterization
      significantly improves clinically relevant aspects of the procedure.

PMID- 24588457
TI  - Gaucher disease: haematological presentations and complications.
AB  - Gaucher disease (GD) is an autosomal recessive lysosomal storage disease, caused
      by deficiency of the enzyme glucocerebrosidase, required for the degradation of
      glycosphingolipids. Clinical manifestations include hepatosplenomegaly,
      thrombocytopenia, bone disease and a bleeding diathesis, frequently resulting in
      presentation to haematologists. Historically managed by splenectomy, transfusions
      and orthopaedic surgery, the development of specific therapy in the form of
      intravenous enzyme replacement therapy in the 1990s has resulted in dramatic
      improvements in haematological and visceral disease. Recognition of
      complications, including multiple myeloma and Parkinson disease, has challenged
      the traditional macrophage-centric view of the pathophysiology of this disorder.
      The pathways by which enzyme deficiency results in the clinical manifestations of
      this disorder are poorly understood; altered inflammatory cytokine profiles,
      bioactive sphingolipid derivatives and alterations in the bone marrow
      microenvironment have been implicated. Further elucidating these pathways will
      serve to advance our understanding not only of GD, but of associated disorders. 

PMID- 24588458
TI  - Pd(OAc)2-catalyzed macrocyclization of 1,2-diazonaphthoquinones with cyclic
      ethers.
AB  - Pd(OAc)2 was found to be an efficient catalyst for the macrocyclization of 1,2
      diazonaphthoquinones and cyclic ethers. This transformation serves as an
      efficient method for the synthesis of protected 1,2-naphthalenediols. 

PMID- 24588459
TI  - Kinetic modeling of inherent mineral catalyzed NO reduction by biomass char.
AB  - The evolution of rice straw char reactivity during reaction with NO was examined
      in differential reactor at 900 and 1000  degrees C. Original and acid-washed rice
      straw chars were used. Surface area and mineral content of char samples with
      different conversion were analyzed. The reactivity of the acid-washed char
      increased until conversion Xchar = 20%, remained constant, and then decreased
      continuously to zero. The reactivity of the original char decreased continuously
      to zero throughout the reaction, with a faster decrease at 1000  degrees C.
      Mineral transformation during original char reaction was obvious. Concentration
      of acid-soluble K decreased about 56% and 90% at 900 and 1000  degrees C. Ca and
      Mg released little to gas phase, but reacted with SiO2 in a small amount. The
      evolution of the acid-washed char reactivity correlated well with the development
      of surface area and was well predicted by random pore model. The reactivity of
      the original char depended not only on the development of surface area, but also
      on transformation of inherent minerals, mainly K. A two-reaction model was built
      which well predicted inherent K transformation. A modified random pore model was
      developed, which successfully simulated inherent mineral catalyzed char-NO
      reaction. 

PMID- 24588460
TI  - Predicting success: optimizing phase II ALS trials for the transition to phase
      III.
AB  - Amyotrophic lateral sclerosis (ALS) research is advancing quickly, but the
      transition from phase II to phase III trials remains particularly challenging. In
      part, this is because of the paradox of phase II ALS trials - they are expected
      to inform researchers about safety, tolerability, dosage selection, and efficacy
      using a small number of patients, and relying on essentially the same outcome
      measures used in phase III trials. We examined pharmacokinetics in the
      cerebrospinal fluid and pharmacodynamic markers to demonstrate target engagement.
      In addition, primary outcome measures are often not specified or do not reach pre
      specified goals for significance. We conclude that future trials should include
      pharmacokinetic (preferably in CSF) and pharmacodynamic markers of target
      engagement when possible. Primary endpoints should be pre-specified. Inclusion
      criteria should be used to reduce heterogeneity and target a relevant
      subpopulation of people with ALS when possible. Multiple phase II trials might be
      required before moving to a large phase III trial.

PMID- 24588461
TI  - Non-invasive ventilation in amyotrophic lateral sclerosis. Hypoventilation and
      oxygen desaturation: two faces of the same coin?

PMID- 24588463
TI  - RETENTIVENESS OF VARIOUS LUTING AGENTS USED WITH IMPLANT SUPPORTED- PROSTHESIS:
      AN INVITRO STUDY.
AB  - Abstract ABSTRACT:Purpose: Desired retrievability of cemented implant-supported
      fixed prosthesis makes the retentive strength of cementing agents an important
      consideration. The aim of the study was to evaluate the retentiveness of
      purposely-designed implant cement and to compare its retentiveness with dental
      cements that are commonly used with implant systems.Materials and method: Ten
      implant analogs were embedded in auto-polymerizing acrylic resin blocks and
      titanium abutments were attached to them. 50 standardized copings were waxed
      directly on the abutment and casted. The cements used were: 1. resin-bonded zinc
      oxide eugenol cement (Kalzinol, DPI), 2. purposely-designed implant cement
      (Premier implant cement), 3. zinc phosphate cement (DeTrey Zinc, Dentsply), 4.
      zinc polycarboxylate cement (Poly-F, Dentsply) and 5. glass ionomer cement (GC
      Gold Label, GC corporation, Japan). After cementation, each sample was subjected
      to a pull-out test using universal testing machine and loads required to remove
      the crowns were recorded. The mean values and standard deviations of cement
      failure loads were analyzed using ANOVA and Bonferroni test.Results: The mean
      values (+/-SD) of loads at failure (n = 10) for various cements were as follows
      (N): resin-bonded zinc oxide eugenol cement 394.62 (+/-9.76), Premier implant
      cement 333.86 (+/-18.91), zinc phosphate cement 629.30 (+/-20.65), zinc
      polycarboxylate cement 810.08 (+/-11.52) and glass ionomer cement 750.17 (+/
      13.78).Conclusions: The results do not suggest that one cement type is better
      than another, but they do provide a ranking order of the cements in their ability
      to retain the prosthesis and to facilitate its easy retrievability.

PMID- 24588462
TI  - 3D Electrospun scaffolds promote a cytotrophic phenotype of cultured primary
      astrocytes.
AB  - Astrocytes are a target for regenerative neurobiology because in brain injury
      their phenotype arbitrates brain integrity, neuronal death and subsequent repair
      and reconstruction. We explored the ability of 3D scaffolds to direct astrocytes
      into phenotypes with the potential to support neuronal survival. Poly-epsilon
      caprolactone scaffolds were electrospun with random and aligned fibre
      orientations on which murine astrocytes were sub-cultured and analysed at 4 and
      12 DIV. Astrocytes survived, proliferated and migrated into scaffolds adopting 3D
      morphologies, mimicking in vivo stellated phenotypes. Cells on random poly
      epsilon-caprolactone scaffolds grew as circular colonies extending processes deep
      within sub-micron fibres, whereas astrocytes on aligned scaffolds exhibited
      rectangular colonies with processes following not only the direction of fibre
      alignment but also penetrating the scaffold. Cell viability was maintained over
      12 DIV, and cytochemistry for F-/G-actin showed fewer stress fibres on
      bioscaffolds relative to 2D astrocytes. Reduced cytoskeletal stress was confirmed
      by the decreased expression of glial fibrillary acidic protein. PCR demonstrated
      up-regulation of genes (excitatory amino acid transporter 2, brain-derived
      neurotrophic factor and anti-oxidant) reflecting healthy biologies of mature
      astrocytes in our extended culture protocol. This study illustrates the
      therapeutic potential of bioengineering strategies using 3D electrospun scaffolds
      which direct astrocytes into phenotypes supporting brain repair. Astrocytes exist
      in phenotypes with pro-survival and destructive components, and their biology can
      be modulated by changing phenotype. Our findings demonstrate murine astrocytes
      adopt a healthy phenotype when cultured in 3D. Astrocytes proliferate and extend
      into poly-epsilon-caprolactone scaffolds displaying 3D stellated morphologies
      with reduced GFAP expression and actin stress fibres, plus a cytotrophic gene
      profile. Bioengineered 3D scaffolds have potential to direct inflammation to aid
      regenerative neurobiology. 

PMID- 24588464
TI  - Effects of amlodipine and perindoprilate on the structure and function of
      mitochondria in ventricular cardiomyocytes during ischemia-reperfusion in the
      pig.
AB  - The aim of this study was to determine whether amlodipine and/or perindoprilate
      injected intravenously (iv) prior to ischemia exerted protective effects on
      mitochondria structural and functional alterations induced by ischemia and
      aggravated by reperfusion. Heart rate, the duration of monophasic action
      potentials (dMAP), peak of the time derivative of left ventricular pressure (LV
      dP/dt max), mitochondria structural and functional parameters in the left
      ventricle ischemic area were measured after 45-min ischemia and 1-min reperfusion
      in domestic pigs either untreated or pretreated with amlodipine, perindoprilate
      or amlodipine + perindoprilate. Ischemia-reperfusion (I/R) induced tachycardia,
      reduced dMAP and LV dP/dt max, and causes alterations of mitochondria structural
      and functional parameters with decreased oxygen consumption, increased reactive
      oxygen species production and reduced calcium retention capacity (CRC) with
      opening of mitochondrial permeability transition pores. This opening is mainly
      due to oxidative stress and calcium overload and seems to be the pivotal event in
      cell death after I/R. No drug treatment changed haemodynamic and
      electrophysiological parameters, but amlodipine and perindoprilate, either alone
      or combined, prevented mitochondrial alterations but only partially. The
      preservation of mitochondrial structure and functions reported in our study
      probably plays an important role in preventing calcium overload and mPTP opening
      during myocardial I/R by a specially increased CRC, which can explain their
      cardioprotective effects. 

PMID- 24588465
TI  - Vestibular involvement in peripheral neuropathy: a review.
AB  - OBJECTIVE: This paper reviews the current literature on involvement of the
      vestibular division of the eighth cranial nerve in peripheral neuropathies. The
      literature abounds with references to auditory neuropathy, which is frequently
      related to more generalized neuropathies, but there is a marked paucity of work
      regarding vestibular neuropathy. A brief overview of neuropathies and the anatomy
      of the vestibulocochlear nerve provide the background for a review of the
      literature of vestibular nerve involvement in a range of neuropathies. DESIGN: A
      literature search including textbooks, and peer-reviewed published journal
      articles in online bibliographic databases was conducted. STUDY SAMPLE: Two
      databases for medical research were included in this review. RESULTS: The review
      of the literature indicates that vestibular involvement is a common and
      consistent finding in many peripheral neuropathies of different aetiologies.
      Specifically, if patients present unsteadiness/ataxia out of proportion to
      objective signs of somatosensory loss or muscle weakness. CONCLUSION: This review
      concludes that vestibular neuropathy, is common in peripheral neuropathy and
      should be identified to optimize patient management and rehabilitation.

PMID- 24588466
TI  - Bone conduction hearing sensitivity in normal-hearing subjects: transcutaneous
      stimulation at BAHA vs BCI position.
AB  - OBJECTIVE: Bone conduction (BC) stimulation closer to the cochlea has previously
      been shown to give higher cochlear promontory acceleration measured by laser
      Doppler vibrometry (LDV). This study is investigating whether stimulation closer
      to the cochlea also gives improved hearing sensitivity. Furthermore, the study
      compares shifts in hearing sensitivity (BC thresholds) and ear-canal sound
      pressure (ECSP). DESIGN: BC hearing thresholds and ECSP have been measured for
      stimulation at two positions: the existing bone-anchored hearing aid (BAHA)
      position, and a new bone conduction implant (BCI) position that is located closer
      to the cochlea. STUDY SAMPLE: The measurements were made on 20 normal-hearing
      subjects. RESULTS: Depending on frequency, the ipsilateral hearing threshold was
      3-14 dB better, and the ipsilateral ECSP was 2-12 dB higher for the BCI than for
      the BAHA position, with no significant differences between threshold and ECSP
      shifts at group level for most frequencies, and individually only for some
      subjects. CONCLUSIONS: It was found that both the objective ECSP and the
      subjective hearing threshold measurements gave similar improvement as previous
      LDV measurements for stimulation closer to the cochlea. One exception was that
      the LDV measurements did not show the improved sensitivity for frequencies below
      500 Hz found here.

PMID- 24588467
TI  - Anti-infective use in children and pregnancy: current deficiencies and future
      challenges.
AB  - There are a number of challenges to using anti-infective agents in children and
      pregnant women. There is limited understanding of the altered pharmacokinetics of
      anti-infectives in these populations and as a result, optimized dosing regimens
      are yet to be established. The potential adverse effects of the drug on pregnancy
      outcome and the developing foetus is a major consideration, and the long term
      implications of drug side effects must be taken into account when drug exposure
      occurs early in life. These factors hinder research and licensing of new anti
      infective drugs in these populations. We describe the current deficiencies and
      future challenges of anti-infective use in children and pregnant women, providing
      specific examples. 

PMID- 24588469
TI  - Linguistic markers of specific language impairment in bilingual children: the
      case of verb morphology.
AB  - This study investigates verbal morphology in Specific Language Impairment (SLI)
      in German, focusing on past participle inflection. Longitudinal data from 12
      German-speaking children with SLI, six monolingual and six Turkish-German
      sequential bilingual children, were examined, plus an additional group of six
      typically developing Turkish-German sequential bilingual children. In a recent
      study (Rothweiler, M., Chilla, S., & H. Clahsen. (2012). Subject verb agreement
      in Specific Language Impairment: A study of monolingual and bilingual German
      speaking children. Bilingualism: Language and Cognition, 15, 39-57), the same
      children with SLI were found to be severely impaired in reliably producing
      correct agreement-marked verb forms. By contrast, the new results reported in
      this study show that both the monolingual and the bilingual children with SLI
      produce participle inflection according to their language age. Our results
      strengthen the case of difficulties with agreement as a linguistic marker of SLI
      in German and show that it is possible to identify SLI from an early sequential
      bilingual child's performance in one of her two languages.

PMID- 24588468
TI  - The use of negative inflections by Finnish-speaking children with and without
      specific language impairment.
AB  - Children with specific language impairment (SLI) have difficulty expressing
      subject-verb agreement. However, in many languages, tense is fused with
      agreement, making it difficult to attribute the problem to agreement in
      particular. In Finnish, negative markers are function words that agree with the
      subject in person and number but do not express tense, providing an opportunity
      to assess the status of agreement in a more straightforward way. Fifteen Finnish
      speaking preschoolers with SLI, 15 age controls and 15 younger controls responded
      to items requiring negative markers in first person singular and plural, and
      third person singular and plural. The children with SLI were less accurate than
      both typically developing groups. However, their problems were limited to
      particular person-number combinations. Furthermore, the children with SLI
      appeared to have difficulty selecting the form of the lexical verb that should
      accompany the negative marker, suggesting that agreement was not the sole
      difficulty.

PMID- 24588470
TI  - The role of language familiarity in bilingual stuttering assessment.
AB  - The aim of this study was to evaluate the ability of English-speaking speech
      language pathologists (SLPs) to evaluate stuttering behaviour in two Spanish
      English bilingual adults who stutter (AWS1 and AWS2). The English-speaking SLPs
      were asked to judge the frequency, severity, type, duration, and physical
      concomitants of stuttering in both languages of the two AWS. The combined results
      from the English-speaking SLPs were then compared to the judgements of three
      Spanish-English bilingual SLPs. Results indicated that English-speaking SLPs (1)
      judged stuttering frequency to be greater in Spanish than English for AWS1, and
      equal in Spanish and English for AWS2, (2) were more accurate at evaluating
      individual moments of stuttering for the English samples compared to the Spanish
      samples, (3) identified fewer and less severe stuttering behaviours than the
      bilingual SLPs in both languages, and (4) were accurate judges of overall
      stuttering severity in both languages. The results correspond to past research
      examining the accuracy of stuttering evaluations in unfamiliar languages.
      Possible explanations for the findings, clinical implications, and future
      research directions are discussed.

PMID- 24588471
TI  - A multidimensional view of gradient change in velar acquisition in three-year
      olds receiving phonological treatment.
AB  - The acquisition of phonemes does not occur in an "all or nothing" manner;
      instead, children gradually acquire dimensions of phonological knowledge. This
      gradual acquisition of phonemes is explored in the present study by comparing
      three types of measures taken from speech samples of three preschool-aged girls
      with a Speech Sound Disorder. The process of acquisition of velar stops was
      measured during 16 weeks of Cycles based speech treatment. Three types of
      measures were used to study the gradual acquisition of velar stops: acoustic
      analyses using voice onset time (VOT) for initial consonants and vowel duration
      for final consonants, speech adaptability using the Glaspey Dynamic Assessment of
      Phonology, and phonetic accuracy based on phonetic transcription. The children
      were assessed prior-to, after 8, and after 16 sessions of treatment based on a
      modified Cycles approach. At the onset of the study, the children had begun the
      process of acquiring velar stops. Differences on acoustic measures and speech
      adaptability measures were observed for velars that were not reflected in the
      phonetic transcription. The acoustic analyses and the speech adaptability
      measures were more sensitive and incremental in showing change over time when
      compared to phonetic transcription, with fewer ceiling and floor effects across
      the children. Although the individual profiles of gradient change were not
      simple, the acoustic and adaptability measures provided additional information
      regarding gradient change, and support our argument that a necessary approach is
      one that describes multiple dimensions of a child's phonological knowledge.

PMID- 24588472
TI  - Memorial of V. Gene Erwin 1937-2013.

PMID- 24588473
TI  - Comparative analysis of flavonoids and polar metabolite profiling of Tanno
      original and Tanno-high rutin buckwheat.
AB  - Rutin is an important indicator for evaluating the quality of buckwheat. In this
      study, flavonoid biosynthesis was compared between two common cultivars (an
      original and a high-rutin line) of buckwheat, Fagopyrum esculentum Moench.
      Transcriptional levels of the main flavonoid biosynthetic genes were analyzed by
      real-time PCR, and main flavonoid metabolites were detected by high-performance
      liquid chromatography (HPLC); levels of gene expression varied among organs of
      the two cultivars. Significantly higher transcription levels of most flavonoid
      biosynthetic genes, except FeFLS1, were detected in stems of the high-rutin line
      than in stems of the original line. FeCHI and FeFLS2 genes also showed higher
      expression levels in seeds of the high-rutin cultivar. In contrast, FePAL, FeC4H,
      Fe4CL1, FeCHS, FeF3H, FeF3'H, FeFLS2, and FeDFR were highly detected in the roots
      of the original line. The HPLC results indicated 1.73-, 1.62-, and 1.77-fold
      higher accumulation of rutin (the primary flavonoid compound) in leaves, stems,
      and mature seeds of the high-rutin cultivar (24.86, 1.46, and 1.36 MUg/mg,
      respectively) compared with the original cultivar (14.40, 0.90, and 0.77 MUg/mg,
      respectively). A total of 46 metabolites were identified from seeds by gas
      chromatography-time-of-flight mass spectrometry. The metabolite profiles were
      subjected to principal component analysis (PCA). PCA could clearly differentiate
      the original and high-rutin cultivars. Our results indicate that the high-rutin
      cultivar could be an excellent alternative for buckwheat culture, and we provide
      useful information for obtaining this cultivar. 

PMID- 24588474
TI  - Making contact with the primitive mind: the contact-barrier, beta-elements and
      the drives.
AB  - A clinical vignette is used as the starting point for an exploration of Bion's
      notion of a contact-barrier, which "separates mental phenomena into two groups
      one of which performs the functions of consciousness and the other the functions
      of unconsciousness" (Bion, 1962a, p. 22), and its relation to Freud's drive
      theory. Bion's concept is compared to Freud's (1950[1895]) description of the
      'contact-barrier' in the Project for a scientific psychology. Through this
      comparison, light is shed on various aspects of Bion's metapsychology, especially
      on the notion of 'beta-elements', described by Bion in quantitative/energetic
      terms as 'accretions of stimuli'. The processing of beta-elements through the
      function of the contact-barrier is understood as an elaboration of Freud's notion
      of the 'binding' of the drives, with the difference that beta-elements encompass
      'unprocessed' external stimuli as well as impulses arising from within. The 'beta
      element' and the 'drives' are both understood as concepts that delimit what is
      knowable in the psyche. Further clinical material is presented to illustrate the
      author's argument that Bion's contact-barrier and related concepts (alpha
      function, containment) should be understood with reference to the
      economic/energetic aspect of Freud's metapsychology. 

PMID- 24588476
TI  - The life of PAI.

PMID- 24588477
TI  - Pediatric Allergy Research--are we on the right track?

PMID- 24588478
TI  - Fetal and early-life origins of allergy.

PMID- 24588479
TI  - Will we be able to reverse the epidemiological trend?

PMID- 24588480
TI  - Prevention--what is the most promising approach?

PMID- 24588481
TI  - Allergen-specific immunoprophylaxis: toward secondary prevention of allergic
      rhinitis?

PMID- 24588482
TI  - Pediatric Asthma--do we need more innovation for treatment?

PMID- 24588483
TI  - What is needed for allergic children?

PMID- 24588484
TI  - Food allergy: a winding road to the present.

PMID- 24588485
TI  - Primary immunodeficiences--options for the future.

PMID- 24588487
TI  - An electrochemical quartz crystal microbalance study of a prospective alkaline
      anion exchange membrane material for fuel cells: anion exchange dynamics and
      membrane swelling.
AB  - A strategy has been devised to study the incorporation and exchange of anions in
      a candidate alkaline anion exchange membrane (AAEM) material for alkaline fuel
      cells using the electrochemical quartz crystal microbalance (EQCM) technique. It
      involves the electro-oxidation of methanol (CH3OH) under alkaline conditions to
      generate carbonate (CO3(2-)) and formate (HCOO(-)) ions at the electrode of a
      quartz crystal resonator coated with an AAEM film, while simultaneously
      monitoring changes in the frequency (Deltaf) and the motional resistance
      (DeltaR(m)) of the resonator. A decrease in Deltaf, indicating an apparent mass
      increase in the film, and a decrease in DeltaR(m), signifying a deswelling of the
      film, were observed during methanol oxidation. A series of additional QCM
      experiments, in which the effects of CH3OH, CO3(2-), and HCOO(-) were
      individually examined by changing the solution concentration of these species,
      confirmed the changes to be due to the incorporation of electrogenerated CO3(2
      )/HCOO(-) into the film. Furthermore, the AAEM films were found to have finite
      anion uptake, validating the expected tolerance of the material to salt
      precipitation in the AAEM. The EQCM results obtained indicated that HCOO(-) and
      CO3(2-), in particular, interact strongly with the AAEM film and readily displace
      OH(-) from the film. Notwithstanding, the anion exchange between CO3(2-)/HCOO(-)
      and OH(-) was found to be reversible. It is also inferred that the film exhibits
      increased swelling in the OH(-) form versus the CO3(2-)/HCOO(-) form. Acoustic
      impedance analysis of the AAEM-film coated quartz resonators immersed in water
      showed that the hydrated AAEM material exhibits significant viscoelastic effects
      due to solvent plasticization.

PMID- 24588489
TI  - Impact of oral diseases and disorders on oral-health-related quality of life of
      children with cerebral palsy.
AB  - The aim of this study was to investigate the impact of oral diseases and
      disorders on the oral-health-related quality of life (OHRQoL) of children with
      CP, adjusting this impact by socioeconomic factors. Data were collected from 60
      pairs of parents-children with CP. Parents answered the child oral health quality
      of life questionnaire (parental-caregivers perception questionnaire and family
      impact scale) and a socioeconomic questionnaire. Dental caries experience,
      traumatic dental injuries, malocclusions, bruxism, and dental fluorosis were also
      evaluated. The multivariate adjusted model showed that dental caries experience
      (p < 0.001) and the presence of bruxism had a negative impact (p = 0.046) on the
      OHRQoL. A greater family income had a positive impact on it (p < 0.001). Dental
      caries experience and bruxism are conditions strongly associated with a negative
      impact on OHRQoL of children with CP and their parents, but a higher family
      income can improve this negative impact. 

PMID- 24588490
TI  - Long-term effects of using oral care aides at a nursing home for elderly
      dependent residents--a pilot study.
AB  - The oral health status of elderly dependent residents is reported to be poor, as
      well as difficult to describe. Analysis of oral microbial flora has been
      suggested as a suitable measurement method. Oral care aides have been shown to
      have a positive influence on oral health care in nursing. The outcome of an
      intervention with oral care aides was followed during a two-year period by
      recording: (a) the proportion of opportunistic microorganisms and bacteria
      associated with caries (b) whether oral hygiene assistance were given to the
      residents or not, and (c) individual experiences concerning oral health care
      among the staff involved. The oral flora and the amount of oral hygiene
      assistance improved throughout the entire study period, but staff interviews
      revealed that it took two years for good cooperation and prophylactic routines to
      be established. An unexpected finding was the positive correlation (p = .0005)
      between a high proportion of the opportunistic microorganisms and death within
      one year. 

PMID- 24588491
TI  - Oral health care provided by Greek dentists to persons with physical and/or
      intellectual impairment.
AB  - PURPOSE: The study aimed to register information about the oral health care
      provided to persons with physical and intellectual impairment (PPII) in Greece
      and to report the dentists' attitudes towards the provision of oral health care.
      METHODS: A well-designed questionnaire was used to select information on
      dentists' socioeconomic data, their office characteristics, the performed oral
      health care and their views about oral health care delivery for PPII. The final
      sample consisted of 534 dentists. Descriptive statistics and Analysis of Variance
      (ANOVA) has been used for the statistical analysis of the data. RESULTS: Most
      respondents were general practitioners (79.3%) providing oral health care to
      PPII, but seven out of ten dentists have not been trained to treat them.
      According to their opinion, oral health care for PPII demands a lot of time and
      is hard to accomplish. CONCLUSIONS: Continuing education and training of dentists
      to treat PPII is essential in Greece.

PMID- 24588492
TI  - The effect of speech therapy on acoustic speech characteristics of cleft lip and
      palate patients: a preliminary study.
AB  - PURPOSE: To assess the effects of speech therapy on the acoustic characteristics
      of speech in a group of cleft lip and palate patients. MATERIALS AND METHODS: In
      this experimental pilot study, eight patients with unilateral cleft lip and
      palate participated in the 13-month period of speech therapy. They had some
      exercises in the class and at home to reduce the hypernasality of speech. Using
      an acoustic software named Praat, three formants (F1, F2, F3) of speech sounds /b
      /, /p /, /f /, /v /, /k /, and /g / were obtained pre and post speech therapy. We
      used paired samples t-test to compare the acoustic variables of each consonant
      before and after the therapy. RESULTS: No significant differences were found
      between the pre- and posttherapy acoustic measures for fricative consonants /f /,
      /v / and stop consonants /k / and /g/. However, a statistically significant
      improvement in hypernasality of labial consonants /b / and /p / was observed
      after the speech therapy. CONCLUSIONS: The present study underlines the role of a
      speech therapist in a complete cleft care team, in order to take care of the
      speech improvement of the patient and to motivate the parents to help the speech
      development of their child.

PMID- 24588493
TI  - Addressing the oral healthcare needs of special needs children: pediatric nurses'
      self-perceived effectiveness.
AB  - OBJECTIVES: To examine the oral health knowledge and practices of pediatric
      nurses who coordinate healthcare services for special needs children and to
      identify those factors that influenced their perceived effectiveness in managing
      their patients' oral health needs. METHODS: Self-reported data were collected
      from 376 nurses employed at Children's Medical Services who responded to an
      online survey. Likert scale scores were used to specifically assess the nurses'
      perceived effectiveness in addressing the oral health needs of special needs
      children. RESULTS: Characteristics significantly associated with special needs
      pediatric nurses who described themselves as "effective or very effective"
      included: the self-perception of being very knowledgeable about basic oral
      health, receiving four or more hours of continuing education training, and
      securing dental appointments for the majority of their pediatric special needs
      patients with minimal waiting times. CONCLUSION: Findings reveal that oral health
      knowledge significantly influenced nurses' perceived effectiveness in addressing
      the oral health needs of special needs children, as well as their ability to
      secure timely dental appointments. These results support the need to incorporate
      oral health education into nursing curricula and expand upon the dental workforce
      available and willing to treat disabled patients.

PMID- 24588494
TI  - A rare presentation of multiple primary squamous cell carcinoma of the tongue in
      a patient with recurrent hepatitis C infection.
AB  - Hepatitis C virus (HCV) infection has been implicated as a risk factor for
      development of oral squamous cell carcinoma (SCC). Multiple primary sites of oral
      SCC associated with HCV infection occurs infrequently. This case report describes
      a rare presentation of multiple primary SCCs of the tongue in a patient with
      recurrent HCV cirrhosis status post liver transplant that required
      interdisciplinary medical and surgical management. It is important for oral
      health care providers to understand the local and systemic implications of HCV
      infection and perform routine clinical examinations to monitor for development of
      oral lesions and associated complications. 

PMID- 24588495
TI  - Oral health of a child being treated for subtype I Gaucher's disease.
AB  - Gaucher disease (GD) is an autosomal recessive disorder characterized by the
      absence of glucosylceramidase. The accumulation of substrates of this enzyme in
      the cytoplasm of cells of the phagocytary system causes skeletal and hematologic
      disorders, and has oral repercussions. This report describes the findings of the
      oral cavity of an 8-year-old diagnosed with subtype I GD who has been receiving
      enzyme replacement therapy for the past 6 years without interruption. The report
      highlights that the child had none of the most common oral disease signs and
      symptoms, which demonstrates the importance of early diagnosis and continuous
      treatment. The article also emphasizes that it is important for dentists to
      recognize oral manifestations of GD (in order to assist in early diagnosis) and
      understand how to treat the likely oral health conditions of GD patients. 

PMID- 24588496
TI  - Data mining for potential adverse drug-drug interactions.
AB  - INTRODUCTION: Patients, in particular elderly ones, frequently receive more than
      one drug at a time. With each drug added to a regime, the number of potential
      drug-drug interactions (DDIs) increases by a power law. Early prediction of
      relevant interactions by computerized tools greatly aids clinicians and can guide
      their prescribing choices. AREAS COVERED: In this article, we discuss different
      types of DDIs, on which levels they can arise and what efforts have been made in
      the past to detect and predict them. The emphasis is on data mining technology
      and network analysis, but overlaps with traditional pharmacovigilance are also
      discussed. Finally, we discuss strategies to focus and simplify mining efforts to
      get meaningful results with less effort. EXPERT OPINION: The necessary technology
      for detecting adverse DDIs exists and is quite refined, although it is more often
      implied in lower risk scenarios (such as syntactic analysis in web searches and
      online libraries). Data mining for DDIs, on the other hand, still requires a
      great deal of human intervention, not only to validate the results but also, more
      importantly, to separate the relevant from the spurious. The fields of network
      analysis and graph theory show great promise but have not yet shown much beyond
      descriptive analyses.

PMID- 24588497
TI  - Microscale mapping of alteration conditions and potential biosignatures in
      basaltic-ultramafic rocks on early Earth and beyond.
AB  - Subseafloor environments preserved in Archean greenstone belts provide an
      analogue for investigating potential subsurface habitats on Mars. The c. 3.5-3.4
      Ga pillow lava metabasalts of the mid-Archean Barberton greenstone belt, South
      Africa, have been argued to contain the earliest evidence for microbial
      subseafloor life. This includes candidate trace fossils in the form of titanite
      microtextures, and sulfur isotopic signatures of pyrite preserved in metabasaltic
      glass of the c. 3.472 Ga Hooggenoeg Formation. It has been contended that similar
      microtextures in altered martian basalts may represent potential extraterrestrial
      biosignatures of microbe-fluid-rock interaction. But despite numerous studies
      describing these putative early traces of life, a detailed metamorphic
      characterization of the microtextures and their host alteration conditions in the
      ancient pillow lava metabasites is lacking. Here, we present a new nondestructive
      technique with which to study the in situ metamorphic alteration conditions
      associated with potential biosignatures in mafic-ultramafic rocks of the
      Hooggenoeg Formation. Our approach combines quantitative microscale compositional
      mapping by electron microprobe with inverse thermodynamic modeling to derive low
      temperature chlorite crystallization conditions. We found that the titanite
      microtextures formed under subgreenschist to greenschist facies conditions. Two
      chlorite temperature groups were identified in the maps surrounding the titanite
      microtextures and record peak metamorphic conditions at 315 +/- 40 degrees C
      (XFe3+(chlorite) = 25-34%) and lower-temperature chlorite veins/microdomains at T
      = 210 +/- 40 degrees C (lower XFe3+(chlorite) = 40-45%). These results provide
      the first metamorphic constraints in textural context on the Barberton titanite
      microtextures and thereby improve our understanding of the local preservation
      conditions of these potential biosignatures. We suggest that this approach may
      prove to be an important tool in future studies to assess the biogenicity of
      these earliest candidate traces of life on Earth. Furthermore, we propose that
      this mapping approach could also be used to investigate altered mafic-ultramafic
      extraterrestrial samples containing candidate biosignatures.

PMID- 24588498
TI  - Paramagnetic iron-doped hydroxyapatite nanoparticles with improved metal sorption
      properties. A bioorganic substrates-mediated synthesis.
AB  - This paper describes the synthesis of paramegnetic iron-containing hydroxyapatite
      nanoparticles and their increased Cu(2+) sorbent capacity when using Ca(2+)
      complexes of soluble bioorganic substrates from urban wastes as synthesis
      precursors. A thorough characterization of the particles by TEM, XRD, FTIR
      spectroscopy, specific surface area, TGA, XPS, and DLS indicates that loss of
      crystallinity, a higher specific area, an increased surface oxygen content, and
      formation of surface iron phases strongly enhance Cu(2+) adsorption capacity of
      hydroxyapatite-based materials. However, the major effect of the surface and
      morphologycal modifications is the size diminution of the aggregates formed in
      aqueous solutions leading to an increased effective surface available for Cu(2+)
      adsorption. Maximum sorption values of 550-850 mg Cu(2+) per gram of particles
      suspended in an aqueous solution at pH 7 were determined, almost 10 times the
      maximum values observed for hydroxyapatite nanoparticles suspensions under the
      same conditions. 

PMID- 24588499
TI  - Neurological disorders in the Global Burden of Disease 2010 study.
AB  - BACKGROUND: The Global Burden of Disease study (GBD) is a large international
      initiative to collect and systematize data on disease burden expressed in non
      economic terms, to allow comparisons across different disease conditions and
      countries. OBJECTIVES: To use data from the large GBD 2010 database to determine
      the importance of neurological disorders in Norway, and to compare it with global
      data on the same disorders. MATERIALS AND METHODS: Relevant data were extracted
      from the Lancet publication from December 2012, and from the interactive website
      of the Institute of Health Metrics and Evaluation on GBD. RESULTS: Neurological
      disorders (Alzheimer's disease, Parkinson's disease, multiple sclerosis,
      epilepsy, migraine and tension-type headache, other neurological disorders)
      account for 5-6% of the disease burden in Norway, which is more than it does
      globally. When also stroke, low back pain and neck pain are included, 10% of the
      disease burden in Norway is represented by neurological disorders. CONCLUSIONS:
      Neurological disorders are of great public health importance. This knowledge is
      useful in dimensioning and organizing healthcare systems and necessary when
      planning education of health personnel on all levels.

PMID- 24588500
TI  - Clinical and genetic studies in a family with a novel mutation in the sepiapterin
      reductase gene.
AB  - OBJECTIVES: Sepiapterin reductase deficiency is a rare, but treatable inherited
      disorder of tetrahydrobiopterin and neurotransmitter metabolism. This disorder is
      most probably underdiagnosed. To date, only 44 cases have been described in the
      literature. We present the clinical and genetic investigations in a family with a
      complex movement disorder. MATERIALS AND METHODS: We examined two affected
      sisters and three healthy family members. The cerebrospinal fluid was analyzed
      for neurotransmitter and pterins, and the sepiapterin reductase gene (SPR) was
      sequenced. RESULTS: The sisters had a complex movement disorders with dystonia
      and diurnal fluctuations. Both had oculogyric crises, and the older sister also
      hypersomnia. Both sisters had raised prolactin levels twice above the reference
      level. One sister had a dramatic response to levodopa, the other responded, but
      developed dyskinesia despite low doses. Both patients improved dramatically over
      time with levodopa (2.3 and 1.5 mg/kg/day). Very low levels of homovanillic acid
      and 5-hydroxyindoleacetic acid and increased levels of sepiapterin and
      dihydrobiopterin were measured in the cerebrospinal fluid before treatment. DNA
      analyses revealed a novel homozygous mutation in exon 2 in the SPR gene,
      c.364A>G/p.(Tyr123Cys), located in a highly conserved region in the gene. Both
      parents and the healthy sister were carriers for the same mutation. CONCLUSIONS:
      A new homozygous mutation in the SPR gene was found in two sisters with dopa
      responsive dystonia. This important and treatable neurotransmitter disorder must
      be considered in patients with a complex movement disorder with diurnal
      fluctuations with or without intellectual impairment. Patients with these
      symptoms should undergo levodopa trial, cerebrospinal fluid investigations, and
      genetic analyses.

PMID- 24588501
TI  - Dystonia--new advances in classification, genetics, pathophysiology and
      treatment.
AB  - Dystonia is a heterogeneous movement disorder and has been defined as 'a syndrome
      of sustained muscle contractions, frequently causing twisted and repetitive
      movements, or abnormal postures'. The classification of dystonia has developed
      along with increasing knowledge, and different schemes have been suggested,
      including age at onset, body distribution, and etiology as the main
      differentiating factors. A revised definition and a new classification of
      dystonia have now been proposed by a group of leading dystonia experts and will
      be referred here. The discovery of the first two gene mutations causing primary
      generalized dystonia (DYT1-TOR1A and DYT6-THAP1) has facilitated studies on
      pathogenesis and pathophysiology of primary dystonias, by comparing
      neurophysiology between manifesting and non-manifesting carriers, and by studying
      the molecular biology of the mutant gene products. During recent years, several
      other gene mutations causing primary dystonia, dystonia-plus, and paroxysmal
      dystonia disorders have been discovered. Only during the last year, by the use of
      whole-exome sequencing techniques, mutations in three different genes in families
      with predominantly cervical dystonia were found, which may lead to improved
      insight into the pathogenesis also of the more frequent focal dystonias.
      Botulinum neurotoxin (BoNT) and deep brain stimulation (DBS) have revolutionized
      the symptomatic treatment for dystonia during the last two decades and continue
      to be refined to improve efficacy and expand their indications. Unfortunately, no
      progress has been made in the oral medication of dystonia. Current and future new
      insights into pathogenetic and pathophysiological mechanisms of dystonia will
      hopefully lead to improvement also in this area soon. 

PMID- 24588502
TI  - Advances in genetic diagnosis of neurological disorders.
AB  - Neurogenetics has developed enormously in recent years, and the genetic basis of
      human disorders is being unravelled rapidly. Many neurological disorders are
      Mendelian disorders, caused by mutations in genes involved in normal function of
      the brain, spinal cord, peripheral nerves or muscles. Due to high costs and time
      consuming procedures, genetic tests have normally been performed late in the
      diagnostic process, when clinical examination and other tests have indicated a
      specific gene as the likely disease cause. Many neurological phenotypes are
      genetically very heterogeneous, and testing of all possible disease genes has
      been impossible. As a result, many patients with genetic neurological disorders
      have remained without a specific diagnosis, even when the disease is caused by
      mutations in known disease genes. Recent technological advances, in particular
      next-generation DNA sequencing techniques, have resulted in rapid identification
      of genes involved in Mendelian disorders and provided new possibilities for
      diagnostic genetic testing. The development of methods for coupling targeted
      capture and massively parallel DNA sequencing has made it possible to examine a
      large number of genes in a single reaction. Diagnostic genetic testing can today
      be performed by the use of gene panels and exome sequencing. This allows a more
      precise diagnosis of many neurological disorders, and genetic testing should now
      be considered earlier in the diagnostic procedure. 

PMID- 24588503
TI  - Myasthenia gravis epidemiology in a national cohort; combining multiple disease
      registries.
AB  - OBJECTIVES: There is a wide variation in reported prevalence and incidence of
      myasthenia gravis (MG). In this study, we aimed to evaluate the validity of two
      nationwide databases by comparing prevalence and incidence rates reported from
      three recent studies using the two databases as case-finding method. MATERIALS
      AND METHODS: Two different Norwegian nationwide databases were used: the
      acetylcholine receptor antibody database (reference cohort) and the Norwegian
      Prescription Database (NorPD) (study cohort). Presence of acetylcholine receptor
      antibodies (AChR) is specific for MG. Up to 85% of MG patients are AChR antibody
      positive. All samples from the whole country were tested at one laboratory. NorPD
      contains patient information on all prescriptions of pyridostigmine. RESULTS:
      Prevalence was 131 per million in the study cohort and 145 per million estimated
      from the reference cohort (Jan 1, 2008). No significant difference in prevalence
      between the study cohort and the reference cohort was found (SIR 1.1, 95% CI 1.0
      1.2). The annual incidence rate was 16.0 per million in the study cohort and 8.8
      per million estimated from the reference cohort, twofold more new MG patients
      were found in the study cohort compared to estimated figures from the reference
      cohort (SIR 1.8; 1.4-2.3). CONCLUSIONS: This study confirms an optimal and
      unbiased case finding in both databases. Our calculated prevalence and incidence
      rates are in line with previous population-based studies. There was good
      agreement in prevalence reported from the two databases. The discrepancy in
      incidence is expected to diminish as years of study are increasing in NorPD.

PMID- 24588504
TI  - MRI evaluation of grey matter atrophy and disease course in multiple sclerosis:
      an overview of current knowledge.
AB  - Multiple sclerosis (MS) is characterized by chronic inflammation of the central
      nervous system, and magnetic resonance imaging (MRI) is used as both a diagnostic
      tool and a parameter in the clinical evaluation. Multiple sclerosis was long
      regarded as a disease of the white matter (WM) in the brain, which can be
      visualized by the standard MRI used in daily practice. There is an increasing
      amount of evidence that grey matter (GM) pathology plays a role from the start of
      the MS disease and throughout the clinical course. Grey matter atrophy, both
      cortical and central, is present in the early course of MS and is also related
      above all to cognitive decline, but also to the development of physical
      disability as measured by EDSS. In this article, we give an overview of GM
      atrophy in MS evaluated by MRI and the relation to the clinical course in MS. 

PMID- 24588505
TI  - Mild stroke: safety and outcome in patients receiving thrombolysis.
AB  - OBJECTIVES: The aim of this study was to compare the short-term clinical outcome
      of patients with acute cerebral ischemia and mild symptoms receiving rt-PA with
      that of patients with acute cerebral ischemia and mild symptoms not treated with
      rt-PA, and to investigate the frequency of symptomatic intracranial hemorrhage
      (sICH) in these patients. MATERIALS AND METHODS: All patients with confirmed
      ischemic stroke/TIA and mild symptoms were included. Mild symptoms were defined
      as NIHSS score<=5 on admission. Functional outcome was assessed with modified
      Rankin Scale (mRS) at day 7 or at earlier discharge. Excellent outcome was
      defined as mRS=0. sICH was defined according to both NINDS and ECASS III
      criteria. RESULTS: Of 2753 patients with confirmed ischemic stroke/TIA admitted
      between February 2006 and February 2013, 966 (35.3%) were excluded because of
      having admission NIHSS>5. A total of 1791 patients presented with mild symptoms
      on admission (NIHSS<=5), of which 158 (8.8%) patients received rt-PA. Treatment
      with rt-PA and early admission were independently associated with excellent
      outcome. Higher NIHSS score on admission and prior ischemic stroke were
      independently associated with poor outcome. Three (1.9%) sICH were diagnosed in
      rt-PA-treated patients and one (0.1%) in patients not receiving rt-PA.
      CONCLUSIONS: This study highlights the efficacy of rt-PA in patients with acute
      cerebral ischemia presenting with mild symptoms and confirms the low-risk profile
      of this treatment.

PMID- 24588506
TI  - Diffusion-weighted lesions in acute ischaemic stroke patients with migraine.
AB  - OBJECTIVES: There is increasing knowledge about an association between migraine
      and ischaemic stroke. Cortical spreading depression (CSD) is the probable
      biological substrate of migrainous aura. To investigate the influence of CSD on
      the apparent stroke - migraine association, we hypothesized that magnetic
      resonance (MR) diffusion weighted images of acute ischaemic stroke patients would
      reveal an association between small cortical infarctions and migraine. METHODS:
      We included all patients admitted to the Bergen stroke unit between 2006 and 2012
      with verified acute ischaemic stroke by MR imaging. Patients were grouped in a
      migraine and a no-migraine group. Baseline data and clinical characteristics were
      analysed between the groups. Imaging data were analysed with respect to infarct
      location and size. Multivariate analyses were performed to adjust for confounders
      and provide risk estimates for observed associations. RESULTS: A total of 1703
      subjects were enrolled, 787 subjects were excluded due to uncertain or
      unobtainable migraine diagnosis, leaving 196 and 720 subjects in the migraine and
      no-migraine group, respectively. The migraine group was younger and included a
      higher proportion of females. There were more infarctions due to cardio-embolism
      (P=0.015) and fewer due to small vessel disease (P=0.018) in the migraine group.
      A higher rate of patients in the migraine group presented symptoms from the
      posterior circulation (P=0.008). Migraine was associated with cortical
      infarctions (OR 1.8 CI: 1.3-2.5, P=0.001). Migraine was also associated with
      small infarctions (OR 1.9 CI: 1.04-3.5, P=0.038). CONCLUSIONS: Migraine was
      associated with small cortical infarctions. This association may be due to
      cortical spreading depression.

PMID- 24588507
TI  - Sleep quality and arousal in migraine and tension-type headache: the headache
      sleep study.
AB  - OBJECTIVES: The present paper summarizes and compares data from our studies on
      subjective and objective sleep quality and pain thresholds in tension-type
      headache (TTH), migraine, and controls. MATERIAL AND METHODS: In a blinded
      controlled explorative study, we recorded polysomnography (PSG) and pressure,
      heat, and cold pain thresholds in 34 controls, 20 TTH, and 53 migraine patients.
      Sleep quality was assessed by questionnaires, sleep diaries, and PSG. Migraineurs
      who had their recordings more than 2 days from an attack were classified as
      interictal while the rest were classified as either preictal or postictal.
      Interictal migraineurs (n=33) were also divided into two groups if their headache
      onsets mainly were during sleep and awakening (sleep migraine, SM), or during
      daytime and no regular onset pattern (non-sleep migraine, NSM). TTH patients were
      divided into a chronic or episodic group according to headache days per month.
      RESULTS: Compared to controls, all headache groups reported more anxiety and
      sleep-related symptoms. TTH and NSM patients reported more daytime tiredness and
      tended to have lower pain thresholds. Despite normal sleep times in diary, TTH
      and NSM had increased slow-wave sleep as seen after sleep deprivation.
      Migraineurs in the preictal phase had shorter latency to sleep onset than
      controls. Except for a slight but significantly increased awakening index SM,
      patients differed little from controls in objective measurements. CONCLUSIONS: We
      hypothesize that TTH and NSM patients on the average need more sleep than healthy
      controls. SM patients seem more susceptible to sleep disturbances. Inadequate
      rest might be an attack-precipitating- and hyperalgesia-inducing factor.

PMID- 24588508
TI  - Prevalence of the invasive Rhizocephalan parasite Loxothylacus panopaei in
      Eurypanopeus depressus in South Carolina and genetic relationships of the
      parasite in North and South Carolina.
AB  - The rhizocephalan barnacle Loxothylacus panopaei is a parasitic castrator of
      xanthid crabs that has invaded the U.S. Atlantic coast. It was transported to the
      Chesapeake Bay in the mid-1960s with mud crabs associated with Gulf coast oysters
      and has since spread north to Long Island Sound, New York, and south to Cape
      Canaveral, Florida. Here we report parasite prevalence at 3 South Carolina sites-
      2 from which the parasite had not been previously reported--and examine the
      genetic relationships of North and South Carolina L. panopaei populations
      relative to Gulf of Mexico and other Atlantic coast parasite populations. Total
      L. panopaei prevalence was 24.2% among all 3 sites, with monthly prevalence as
      high as 51.6% at Waties Island, South Carolina. Sequence analyses of North and
      South Carolina specimens revealed the presence of 4 cytochrome c oxidase subunit
      I haplotypes--3 commonly found in other invasive populations and 1 new haplotype
      found in a single specimen from the Rachel Carson Reserve in Carteret County,
      North Carolina--and indicate that the Carolina populations are a result of range
      expansion from the original Atlantic coast invasion.

PMID- 24588509
TI  - Comment on "An evaluation of water quality in private drinking water wells near
      natural gas extraction sites in the barnett shale formation".

PMID- 24588511
TI  - Gender differences in the relationship between serum zinc concentration and
      metabolic syndrome.
AB  - BACKGROUND: Zinc, a co-factor of antioxidant enzymes, may be involved in the
      pathophysiology of metabolic syndrome (MetS). AIM: To determine the association
      between serum zinc concentration and MetS in a population-based study. SUBJECTS
      AND METHODS: In the Tehran Lipid and Glucose Study, serum zinc concentration was
      measured by flame atomic absorption spectrometry in 2626 adult participants.
      After removal of outliers, usable data was available for 2401 participants.
      Dietary zinc was assessed by a validated semi-quantitative food frequency
      questionnaire. RESULTS: Compared to those without the MetS, serum zinc
      concentration was significantly higher in men with syndrome (17.1 +/- 4.9 vs 16.5
      +/- 4.6 MUmol/L, p = 0.035); however, values were comparable in females (16.1 +/-
      4.8 vs 15.8 +/- 4.4, p = 0.460). Men in tertile 3 of serum zinc had significantly
      higher chances of having MetS, even after multivariate adjustment (OR = 1.48, 95%
      confidence interval (CI) = 1.07-2.06, p = 0.020). Women in tertile 2 of serum
      zinc had significantly lower chances of having MetS, which remained significant
      after multivariate adjustment (OR = 0.68, 95% CI = 0.47-0.99, p = 0.046).
      CONCLUSION: This study observed a gender difference between serum zinc and MetS,
      with higher levels being positively associated with MetS in men and having a
      protective effect in women. Further studies are needed to elucidate the role of
      zinc status in the development of MetS.

PMID- 24588510
TI  - Localization of BDNF expression in the developing brain of zebrafish.
AB  - The brain-derived neurotrophic factor (BDNF) gene is expressed in differentiating
      and post-mitotic neurons of the zebrafish embryo, where it has been implicated in
      Huntington's disease. Little is known, however, about the full complement of
      neuronal cell types that express BDNF in this important vertebrate model. Here,
      we further explored the transcriptional profiles during the first week of
      development using real-time quantitative polymerase chain reaction (RT-qPCR) and
      whole-mount in situ hybridization (WISH). RT-qPCR results revealed a high level
      of maternal contribution followed by a steady increase of zygotic transcription,
      consistent with the notion of a prominent role of BDNF in neuronal maturation and
      maintenance. Based on WISH, we demonstrate for the first time that BDNF
      expression in the developing brain of zebrafish is structure specific. Anatomical
      criteria and co-staining with genetic markers (shh, pax2a, emx1, krox20, lhx2b
      and lhx9) visualized major topological domains of BDNF-positive cells in the
      pallium, hypothalamus, posterior tuberculum and optic tectum. Moreover, the
      relative timing of BDNF transcription in the eye and tectum may illustrate a
      mechanism for coordinated development of the retinotectal system. Taken together,
      our results are compatible with a local delivery and early role of BDNF in the
      developing brain of zebrafish, adding basic knowledge to the study of
      neurotrophin functions in neural development and disease. 

PMID- 24588512
TI  - Janet Rowley 1925-2013: a rock star of haematology and genetics.

PMID- 24588514
TI  - Authors' reply.

PMID- 24588515
TI  - SPE-LC-FD determination of polycyclic aromatic hydrocarbon monohydroxy
      derivatives in cephalopods.
AB  - A new analytical methodology, based on liquid chromatography with fluorescence
      detection (LC-FD), after extraction, enzymatic hydrolysis, and solid-phase
      extraction (SPE) through Oasis HLB cartridges, was developed and validated for
      the simultaneous determination of three monohydroxy derivatives of polycyclic
      aromatic hydrocarbons (PAHs). The optimized analytical method is sensitive,
      accurate, and precise, with recoveries between 62 and 110% and limits of
      detection of 227, 9, and 45 ng/g for 1-hydroxynaphthalene, 2-hydroxyfluorene, and
      1-hydroxypyrene, respectively. Their levels were estimated in different
      cephalopod matrices (edible tissues and hemolymph). The methodology was applied
      to samples of the major cephalopod species consumed worldwide. Of the 18 samples
      analyzed, 39% were contaminated with 1-hydroxynaphthalene, which was the only PAH
      metabolite detected. Its concentration ranged from 786 to 1145 ng/g. This highly
      sensitive and specific method allows the identification and quantitation of PAH
      metabolites in forthcoming food safety and environmental monitoring programs. 

PMID- 24588513
TI  - On the need and speed of regulating triclosan and triclocarban in the United
      States.
AB  - The polychlorinated aromatic antimicrobials triclosan and triclocarban are in
      widespread use for killing microorganisms indiscriminately, rapidly, and by
      nonspecific action. While their utility in healthcare settings is undisputed,
      benefits to users of antimicrobial personal care products are few to none. Yet,
      these latter, high-volume uses have caused widespread contamination of the
      environment, wildlife, and human populations. This feature article presents a
      timeline of scientific evidence and regulatory actions in the U.S. concerning
      persistent polychlorinated biocides, showing a potential path forward to
      judicious and sustainable uses of synthetic antimicrobials, including the design
      of greener and safer next-generation alternatives. 

PMID- 24588516
TI  - Cetuximab increases concentrations of irinotecan and of its active metabolite SN
      38 in plasma and tumour of human colorectal carcinoma-bearing mice.
AB  - In a previous study, we showed that cetuximab, a monoclonal antibody directed
      towards epidermal growth factor receptor, could inhibit P-glycoprotein (P-gp), an
      efflux protein of ATP-binding cassette family, and lead to an increased P-gp
      substrate intracellular concentration. Cetuximab is given with irinotecan to
      patients with metastasis colorectal cancer who did not respond to irinotecan
      based therapy. The mechanism of this successful clinical reversion remains
      unknown. As irinotecan is a P-gp substrate, we tested here whether cetuximab
      could modify irinotecan concentration in mice. Therefore, concentrations of
      irinotecan and of its active metabolite SN-38 were measured by HPLC in plasma and
      tumour of mice bearing a human colorectal carcinoma xenograft when irinotecan is
      given orally alone or after a pretreatment with cetuximab. Pharmacokinetic
      analysis showed no significant modification of irinotecan concentrations but a
      significant increase (1.7-fold) in SN-38 AUCs in plasma and in tumour after a
      pretreatment with cetuximab. Those results suggest that cetuximab influence
      irinotecan distribution into tissues probably due to inhibition of P-gp. As SN-38
      is 200-fold more potent than irinotecan, cetuximab could reverse irinotecan
      resistance by an effect on its active metabolite. Inhibiting SN-38 efflux by P-gp
      drug transporters in biliary system and tumour can lead to pharmacokinetic
      modification and a higher anticancer efficacy. 

PMID- 24588517
TI  - Pointing and naming are not redundant: children use gesture to modify nouns
      before they modify nouns in speech.
AB  - Nouns form the first building blocks of children's language but are not
      consistently modified by other words until around 2.5 years of age. Before then,
      children often combine their nouns with gestures that indicate the object labeled
      by the noun, for example, pointing at a bottle while saying "bottle." These
      gestures are typically assumed to be redundant with speech. Here we present data
      challenging this assumption, suggesting that these early pointing gestures serve
      a determiner-like function (i.e., point at bottle + "bottle" = that bottle).
      Using longitudinal data from 18 children (8 girls), we analyzed all utterances
      containing nouns and focused on (a) utterances containing an unmodified noun
      combined with a pointing gesture and (b) utterances containing a noun modified by
      a determiner. We found that the age at which children first produced point + noun
      combinations predicted the onset age for determiner + noun combinations.
      Moreover, point + noun combinations decreased following the onset of determiner +
      noun constructions. Importantly, combinations of pointing gestures with other
      types of speech (e.g., point at bottle + "gimme" = gimme that) did not relate to
      the onset or offset of determiner + noun constructions. Point + noun combinations
      thus appear to selectively predict the development of a new construction in
      speech. When children point to an object and simultaneously label it, they are
      beginning to develop their understanding of nouns as a modifiable unit of speech.

PMID- 24588518
TI  - Your earliest memory may be earlier than you think: prospective studies of
      children's dating of earliest childhood memories.
AB  - Theories of childhood amnesia and autobiographical memory development have been
      based on the assumption that the age estimates of earliest childhood memories are
      generally accurate, with an average age of 3.5 years among adults. It is also
      commonly believed that early memories will by default become inaccessible later
      on and this eventually results in childhood amnesia. These assumptions were
      examined in 2 prospective studies, in which children recalled and dated their
      earliest memories at an initial interview and did it again 1 year (Study 1) and 2
      years later (Study 2). Systematic telescoping errors emerged: Children
      substantially postdated their memories for the same events at the follow-up
      interview, particularly for memories initially dated from earlier ages. These
      findings have critical methodological and theoretical implications for research
      on childhood amnesia and autobiographical memory development.

PMID- 24588519
TI  - Individual differences and age-related changes in divergent thinking in toddlers
      and preschoolers.
AB  - Divergent thinking shows the ability to search for new ideas, which is an
      important factor contributing to innovation and problem solving. Current
      divergent thinking tests allow researchers to study children's divergent thinking
      from the age of 3 years on. This article presents the first measure of divergent
      thinking that can be used with children as young as 2 years. The Unusual Box test
      is a nonverbal and nonimitative test in which children play individually with a
      novel toy and novel objects. Divergent thinking is scored as the number of
      different actions performed. Study 1 shows that the Unusual Box test is a valid
      measure of divergent thinking as it correlates with standard measures of
      divergent thinking in 3- and 4-year-olds. Study 2 indicates that the test can be
      used with 2-year-olds, as it shows high test-retest reliability, demonstrating
      that 2-year-olds can think divergently. Across both studies, individual
      differences and age-related changes were found, indicating that some children are
      better at divergent thinking than others and that children's divergent thinking
      increases with age. This test will allow researchers to gain insight into the
      early emergence of divergent thinking.

PMID- 24588520
TI  - Japanese and American children's moral evaluations of reporting on
      transgressions.
AB  - American and Japanese children's evaluations of the reporting of peers'
      transgressions to authority figures were investigated. Seven-, 9-, and 11-year
      old children (N = 160) and adults (N = 62) were presented with vignettes and were
      asked to evaluate the decisions of child observers who reported their friend's
      either major or relatively minor transgression to a teacher. The results showed
      that, in both countries, participants across all age groups considered it
      appropriate to report major transgressions. However, compared with older
      participants, the youngest children thought it was appropriate to tattle (i.e.,
      to report more minor transgressions). The results also showed a cross-cultural
      difference: Japanese compared with American participants considered it
      appropriate to report minor transgressions. The age-related findings are
      discussed with reference to children's social experience and improving cognition.
      The cross-cultural findings are discussed with reference to potential differences
      in the emphases placed on respecting authority relationships, empathy, and social
      interdependence by the 2 cultures.

PMID- 24588521
TI  - Adaptation to the birth of a child with a congenital anomaly: a prospective
      longitudinal study of maternal well-being and psychological distress.
AB  - This study explores the stability and change in maternal life satisfaction and
      psychological distress following the birth of a child with a congenital anomaly
      using 5 assessments from the Norwegian Mother and Child Cohort Study collected
      from Pregnancy Week 17 to 36 months postpartum. Participating mothers were
      divided into those having infants with (a) Down syndrome (DS; n = 114), (b) cleft
      lip/palate (CLP; n = 179), and (c) no disability (ND; n = 99,122). Responses on
      the Satisfaction With Life Scale and a short version of the Hopkins Symptom
      Checklist were analyzed using structural equation modeling, including latent
      growth curves. Satisfaction and distress levels were highly diverse in the
      sample, but fairly stable over time (retest correlations: .47-.68). However, the
      birth of a child with DS was associated with a rapid decrease in maternal life
      satisfaction and a corresponding increase in psychological distress observed
      between pregnancy and 6 months postpartum. The unique effects from DS on changes
      in satisfaction (Cohen's d = -.66) and distress (Cohen's d = .60) remained
      stable. Higher distress and lower life satisfaction at later assessments appeared
      to reflect a persistent burden that was already experienced 6 months after birth.
      CLP had a temporary impact (Cohen's d = .29) on maternal distress at 6 months.
      However, the overall trajectories did not differ between CLP and ND mothers. In
      sum, the birth of a child with DS influences maternal psychological distress and
      life satisfaction throughout the toddler period, whereas a curable condition like
      CLP has only a minor temporary effect on maternal psychological distress.

PMID- 24588522
TI  - Pubertal timing and adolescent sexual behavior in girls.
AB  - Girls who experience earlier pubertal timing relative to peers also exhibit
      earlier timing of sexual intercourse and more unstable sexual relationships.
      Although pubertal development initiates feelings of physical desire, the
      transition into romantic and sexual relationships involves complex biological and
      social processes contributing both to physical maturation and to individual
      interpretations of pubertal experiences. Using a sample of female sibling pairs
      (n = 923 pairs) from the National Longitudinal Study of Adolescent Health, the
      present study investigated associations among menarche and perceived pubertal
      timing, age of first sexual intercourse (AFI), and adolescent dating and sexual
      behavior using a behavioral genetic approach. Genetic factors influencing age at
      menarche and perceived pubertal timing predicted AFI through shared genetic
      pathways, whereas genetic factors related only to perceived pubertal timing
      predicted engagement in dating, romantic sex, and nonromantic sex in the previous
      18 months. These results suggest that a girl's interpretation of her pubertal
      timing beyond objective timing is important to consider for the timing and the
      contexts of romantic and reproductive behavior.

PMID- 24588523
TI  - AAP centennial commentary: theme 3: Evolution and application of classification
      systems for periodontal diseases--a retrospective commentary*.

PMID- 24588524
TI  - Letter to the editor: Authors' response.

PMID- 24588525
TI  - Letter to the editor: Re: Periodontal condition of patients with autoimmune
      diseases and the effect of anti-tumor necrosis factor-alpha therapy.

PMID- 24588526
TI  - Letter to the editor: Re: The clinical effect of scaling and root planing and the
      concomitant administration of systemic amoxicillin and metronidazole: a
      systematic review; Re: Effectiveness of systemic amoxicillin/metronidazole as
      adjunctive therapy to scaling and root planing in the treatment of chronic
      periodontitis: a systematic review and meta-analysis; Re: Effectiveness of
      systemic amoxicillin/metronidazole as an adjunctive therapy to full-mouth scaling
      and root planing in the treatment of aggressive periodontitis: a systematic
      review and meta-analysis.

PMID- 24588527
TI  - Letter to the editor: Authors' response.

PMID- 24588528
TI  - Comorbidity in adults with hearing difficulties: which chronic medical conditions
      are related to hearing impairment?
AB  - OBJECTIVES: To investigate the occurrence of 27 chronic medical conditions in a
      cohort of adults with and without hearing impairment, and to examine the
      association between these conditions and hearing ability. DESIGN: The National
      Longitudinal Study on Hearing (NL-SH study) is a large prospective study among
      adults aged 18 to 70 years, conducted via the internet in the Netherlands.
      Hearing ability was measured with a digits-in-noise test and comorbidity was
      assessed through self-report. STUDY SAMPLE: Cross-sectional data of 890 hearing
      impaired and 975 normally-hearing adults were analyzed. Both descriptive
      statistics and multinomial logistic regression analyses were conducted. RESULTS:
      Of the NL-SH participants with insufficient or poor hearing ability, 78.5%
      reported to suffer from at least one additional chronic condition. This
      proportion was larger than in the normally-hearing group (68.6% with one or more
      chronic conditions and 37.7% with two or more). After adjustment for age and
      gender, 'dizziness causing falling', 'diabetes' and 'arthritis types other than
      osteoarthritis and rheumatic arthritis' were significantly associated with poor
      hearing ability. CONCLUSIONS: Our results show that some previously reported
      associations do not only occur in older age groups, but also in younger cohorts.
      Comorbidity is relevant in the rehabilitation (multi-disciplinary care) and the
      clinical encounter.

PMID- 24588529
TI  - Nitroepoxides as versatile precursors to 1,4-diamino heterocycles.
AB  - Nitroepoxides are easily transformed into 1,4-diamino heterocycles such as
      quinoxalines and pyrazines by treatment with 1,2-benzenediamines and ammonia,
      respectively. Additionally, related saturated heterocycles, such as piperazines
      and tetrahydroquinoxalines, can be accessed by treatment with 1,2-diamines and a
      reducing agent. These transformations are efficient, provide access privileged,
      bioactive structures, and produce minimal waste. 

PMID- 24588530
TI  - Linking binocular vision neuroscience with clinical practice.

PMID- 24588531
TI  - The case from animal studies for balanced binocular treatment strategies for
      human amblyopia.
AB  - Although amblyopia typically manifests itself as a monocular condition, its
      origin has long been linked to unbalanced neural signals from the two eyes during
      early postnatal development, a view confirmed by studies conducted on animal
      models in the last 50 years. Despite recognition of its binocular origin,
      treatment of amblyopia continues to be dominated by a period of patching of the
      non-amblyopic eye that necessarily hinders binocular co-operation. This review
      summarizes evidence from three lines of investigation conducted on an animal
      model of deprivation amblyopia to support the thesis that treatment of amblyopia
      should instead focus upon procedures that promote and enhance binocular co
      operation. First, experiments with mixed daily visual experience in which
      episodes of abnormal visual input were pitted against normal binocular exposure
      revealed that short exposures of the latter offset much longer periods of
      abnormal input to allow normal development of visual acuity in both eyes. Second,
      experiments on the use of part-time patching revealed that purposeful
      introduction of episodes of binocular vision each day could be very beneficial.
      Periods of binocular exposure that represented 30-50% of the daily visual
      exposure included with daily occlusion of the non-amblyopic could allow recovery
      of normal vision in the amblyopic eye. Third, very recent experiments demonstrate
      that a short 10 day period of total darkness can promote very fast and complete
      recovery of visual acuity in the amblyopic eye of kittens and may represent an
      example of a class of artificial environments that have similar beneficial
      effects. Finally, an approach is described to allow timing of events in kitten
      and human visual system development to be scaled to optimize the ages for
      therapeutic interventions.

PMID- 24588532
TI  - Binocular vision in amblyopia: structure, suppression and plasticity.
AB  - The amblyopic visual system was once considered to be structurally monocular.
      However, it now evident that the capacity for binocular vision is present in many
      observers with amblyopia. This has led to new techniques for quantifying
      suppression that have provided insights into the relationship between suppression
      and the monocular and binocular visual deficits experienced by amblyopes.
      Furthermore, new treatments are emerging that directly target suppressive
      interactions within the visual cortex and, on the basis of initial data, appear
      to improve both binocular and monocular visual function, even in adults with
      amblyopia. The aim of this review is to provide an overview of recent studies
      that have investigated the structure, measurement and treatment of binocular
      vision in observers with strabismic, anisometropic and mixed amblyopia.

PMID- 24588534
TI  - Should amblyopia be treated?

PMID- 24588533
TI  - Responses to interocular disparity correlation in the human cerebral cortex.
AB  - PURPOSE: Perceiving binocular depth relies on the ability of our visual system to
      precisely match corresponding features in the left and right eyes. Yet how the
      human brain extracts interocular disparity correlation is poorly understood.
      METHODS: We used functional magnetic resonance imaging (fMRI) to characterize
      brain regions involved in processing interocular disparity correlation. By
      varying the amount of interocular correlation of a disparity-defined random-dot
      stereogram, we concomitantly controlled the perception of binocular depth and
      measured the percent Blood-Oxygenation-Level-Dependent (%BOLD)-signal in multiple
      regions-of-interest in the human occipital cortex and along the intra-parietal
      sulcus. RESULTS: A linear support vector machine classification analysis applied
      to cortical responses showed patterns of activation that represented different
      disparity correlation levels within regions-of-interest in the visual cortex.
      These also revealed a positive trend between the difference in disparity
      correlation and classification accuracy in V1, V3 and lateral occipital cortex.
      Classifier performance was significantly related to behavioural performance in
      dorsal visual area V3. Cortical responses to random-dot-stereogram stimuli were
      greater in the right compared to the left hemisphere. CONCLUSIONS: Our results
      show that multiple regions in the cerebral cortex are sensitive to changes in
      interocular disparity correlation, and that dorsal area V3 may play an important
      role in the early transformation of binocular disparity to depth perception.

PMID- 24588535
TI  - Bitemporal hemianopia; its unique binocular complexities and a novel remedy.
AB  - Bitemporal hemianopic visual field impairment frequently leads to binocular
      vision difficulties. Patients with bitemporal hemianopia with pre-existing
      exophoria complain of horizontal diplopia, sometimes combined with vertical
      deviation (with pre-existing hyperphoria). The symptoms are a result of the
      phoria decompensating into a tropia (hemi-slide) due to the lack of retinal
      correspondence between the remaining nasal fields of both eyes. We measured these
      effects using a dichoptic perimeter. We showed that aligning the eyes with prisms
      could prevent diplopia if the bitemporal hemianopia is incomplete. We also
      describe the successful use of a novel fusion aid - the 'stereo-typoscope' - that
      utilizes midline stereopsis to prevent diplopia resulting from hemi-sliding in
      patients with complete bitemporal hemianopia.

PMID- 24588536
TI  - Identification of avian malaria (Plasmodium sp.) and canine heartworm
      (Dirofilaria immitis) in the mosquitoes of Tennessee.
AB  - Plasmodium reticulum, the causative agent for avian malaria (a protozoan), and
      Dirofilaria immitis, the causative agent for canine heartworm (a filarial
      nematode), are 2 obligate parasites transmitted by mosquitoes. The objective of
      this project was to identify whether either parasite was present in Tennessee
      mosquitoes and to illustrate the need for collecting spatial and temporal vector
      parasite data. During 2012, mosquitoes were collected from the East Tennessee
      Research and Education Center (ETREC) in eastern Tennessee and the Ames
      Plantation Research and Education Center (AMES) in western Tennessee using CO(2)
      traps and gravid traps. Once mosquitoes were identified to species, their heads
      and thoraces were pooled in groups of <=10, and the entire pool underwent DNA
      extraction and parasite amplification via polymerase chain reaction (PCR) for
      Plasmodium and Haemoproteus parasite DNA (cytochrome b) and for Dirofilaria
      species DNA (internal transcribed spacer-2 ribosomal DNA). All positive PCR
      amplicons were bidirectionally sequenced to confirm positivity and to identify
      the potential parasite genotype. This approach resulted in 762 mosquito pools,
      150 pools from AMES and 612 pools from ETREC. In total, 3,260 mosquitoes were
      collected, representing 28 mosquito species. The 3 abundant genera were Culex
      (2,440 specimens, 74.8%), Aedes (720, 22.1%), and Anopheles (85, 2.6%). The
      remaining specimens included 13 Psorophora, 1 Orthopodomyia signiferia, and 1
      Coquillettidia perturbans. Of the 150 pools from AMES, 1 pool (0.7%) was positive
      for avian malaria and 12 pools (8.0%) were positive for canine heartworm. Of the
      612 pools from ETREC, 61 pools (10.0%) were positive for avian malaria and 8
      pools (1.3%) were positive for canine heartworm. Positive pools for both
      Plasmodium and Dirofilaria were primarily Culex pipiens and occurred later in the
      season. The confirmation of the agents for avian malaria and canine heartworm
      illustrates the need for concurrent spatial and temporal studies using different
      trapping methods. The confirmation of avian malaria and canine heartworm in
      Tennessee illustrates the need for concurrent spatial and temporal studies.
      Future studies incriminating the potential vector populations will begin to
      unravel the complex relationships that intimately tie together hosts, vectors,
      and parasites. Results provide a significant contribution to the knowledge of the
      diversity of mosquito parasites present in Tennessee, and the presence of
      positive field populations warrants additional research exploring the
      environmental factors contributing to transmission.

PMID- 24588537
TI  - Hepatobiliary transporters in drug-induced cholestasis: a perspective on the
      current identifying tools.
AB  - INTRODUCTION: Impaired bile formation leads to the accumulation of cytotoxic bile
      salts in hepatocytes and, consequently, cholestasis and severe liver disease.
      Knowledge of the role of hepatobiliary transporters, especially the bile salt
      export pump (BSEP), in the pathogenesis of cholestasis is continuously
      increasing. AREAS COVERED: This review provides an introduction into the role of
      these transport proteins in bile formation. It addresses the clinical relevance
      and pathophysiologic consequences of altered functions of these transporters by
      genetic mutations and drugs. In particular, the current practical aspects of
      identification and mitigation of drug candidates with liver liabilities employed
      during drug development, with an emphasis on preclinical screening for BSEP
      interaction, are discussed. EXPERT OPINION: Within the potential pathogenetic
      mechanisms of acquired cholestasis, the inhibition of BSEP by drugs is well
      established. Interference of a new compound with BSEP transport activity should
      raise a warning sign to conduct follow-up experiments and to monitor liver
      function during clinical development. A combination of in vitro screening for
      transport interaction, in silico predicting models, and consideration of
      physicochemical and metabolic properties should lead to a more efficient
      screening of potential liver liability.

PMID- 24588538
TI  - Chemical and structural indicators for large redox potentials in Fe-based
      positive electrode materials.
AB  - Li-ion batteries have enabled a revolution in the way portable consumer
      electronics are powered and will play an important role as large-scale
      electrochemical storage applications like electric vehicles and grid-storage are
      developed. The ability to identify and design promising new positive insertion
      electrodes will be vital in continuing to push Li-ion technology to its fullest
      potential. Utilizing a combination of computational tools and structural
      analysis, we report new indicators which will facilitate the recognition of
      phases with the desired redox potential. Most importantly of these, we find there
      is a strong correlation between the presence of Li ions sitting in close
      proximity to the redox center of polyanionic phases and the open circuit voltage
      in Fe-based cathodes. This common structural feature suggests that the bonding
      associated with Li may have a secondary inductive effect which increases the
      ionic character of Fe bonds beyond what is typically expected based purely on
      arguments of electronegativity associated with the polyanionic group. This
      correlation is supported by ab initio calculations which show the Bader charge
      increases (reflecting an increased ionicity) in a nearly linear fashion with the
      experimental cell potentials. These features are demonstrated to be consistent
      across a wide variety of compositions and structures and should help to
      facilitate the design of new, high-potential, and environmentally sustainable
      insertion electrodes. 

PMID- 24588539
TI  - Microbial community structures of novel Icelandic hot spring systems revealed by
      PhyloChip G3 analysis.
AB  - Microbial community profiles of recently formed hot spring systems ranging in
      temperatures from 57 degrees C to 100 degrees C and pH values from 2 to 4 in
      Hveragerdi (Iceland) were analyzed with PhyloChip G3 technology. In total, 1173
      bacterial operational taxonomic units (OTUs) spanning 576 subfamilies and 38
      archaeal OTUs covering 32 subfamilies were observed. As expected, the
      hyperthermophilic (~100 degrees C) spring system exhibited both low microbial
      biomass and diversity when compared to thermophilic (~ 60 degrees C) springs.
      Ordination analysis revealed distinct bacterial and archaeal diversity in
      geographically distinct hot springs. Slight variations in temperature (from 57
      degrees C to 64 degrees C) within the interconnected pools led to a marked
      fluctuation in microbial abundance and diversity. Correlation and PERMANOVA tests
      provided evidence that temperature was the key environmental factor responsible
      for microbial community dynamics, while pH, H2S, and SO2 influenced the abundance
      of specific microbial groups. When archaeal community composition was analyzed,
      the majority of detected OTUs correlated negatively with temperature, and few
      correlated positively with pH.

PMID- 24588541
TI  - Cobalt-catalyzed C-H borylation.
AB  - A family of pincer-ligated cobalt complexes has been synthesized and are active
      for the catalytic C-H borylation of heterocycles and arenes. The cobalt catalysts
      operate with high activity and under mild conditions and do not require excess
      borane reagents. Up to 5000 turnovers for methyl furan-2-carboxylate have been
      observed at ambient temperature with 0.02 mol % catalyst loadings. A catalytic
      cycle that relies on a cobalt(I)-(III) redox couple is proposed. 

PMID- 24588540
TI  - Transplantation of CD3/CD19 depleted allografts from haploidentical family donors
      in paediatric leukaemia.
AB  - Transplantation of T- and B-cell depleted allografts from haploidentical family
      donors was evaluated within a prospective phase II trial in children with acute
      lymphoblastic leukaemia, acute myeloid leukaemia and advanced myelodysplastic
      syndrome (n = 46). 20 patients had active disease; 19 patients received a second
      or third stem cell transplantation (SCT). Toxicity-reduced conditioning regimens
      consisted of fludarabine or clofarabine (in active disease only), thiotepa,
      melphalan and serotherapy. Graft manipulation was carried out with immunomagnetic
      microbeads. Primary engraftment occurred in 88%, with a median time to reach >1.0
      * 109/l leucocytes, >20 * 109/l platelets and >0.1 * 109/l T-cells of 10, 11 and
      50 days, respectively. After retransplantation, engraftment occurred in 100%.
      Acute graft-versus-host disease (GvHD) grade II and III-IV occurred in 20% and
      7%, chronic GvHD occurred in 21%. Both conditioning regimens had comparable
      toxicity. Transplant-related mortality (TRM) was 8% at one year and 20% at 5
      years. Event-free survival at 3 years was: 25% (whole group), 46% (first, second
      or third complete remission [CR], first SCT) vs. 8% (active disease, first SCT)
      and 20% (second or third SCT, any disease status). This approach allows first or
      subsequent haploidentical SCTs to be performed with low TRM. Patients in CR may
      benefit from SCT, whereas the results in patients with active disease were poor.

PMID- 24588542
TI  - Response to comment on "An evaluation of water quality in private drinking water
      wells near natural gas extraction sites in the barnett shale formation".

PMID- 24588543
TI  - Effect of kangaroo mother care on growth and development of low birthweight
      babies up to 12 months of age: a controlled clinical trial.
AB  - AIM: Kangaroo mother care (KMC) is a nonconventional low-cost method of newborn
      care. Our aim was to assess the effect of sustained KMC on the growth and
      development of low birthweight Indian babies up to the age of 12 months. METHODS:
      We enrolled 500 mother and baby pairs, in groups of five, in a parallel group
      controlled clinical trial. The three infants with the lowest birthweight in each
      group received KMC, while the other two received conventional care. All babies
      were exclusively breastfed for 6 months. Babies in the intervention group were
      provided KMC until the infant was 40 weeks of corrected gestation or weighed 2500
      g. Weight, length and head, chest and arm circumferences were evaluated at birth
      and at the corrected ages of 0, 3, 6, 9 and 12 months. Development was assessed
      using the Developmental Assessment Scales for Indian Infants (DASII) at 12
      months. RESULTS: The KMC babies rapidly achieved physical growth parameters
      similar to the control babies at 40 weeks of corrected age. But after that, they
      surpassed them, despite being smaller at birth. DASII motor and mental
      development quotients were also significantly better for KMC babies. CONCLUSION:
      The infants in the KMC group showed better physical growth and development than
      the conventional control group.

PMID- 24588544
TI  - Risk of choriocarcinoma from postpartum placental remnants staying for extended
      times in the uterus.

PMID- 24588545
TI  - Absence of chromosomal abnormalities in herniated orbital fat.
AB  - AIMS: Lipomatous tumours of the orbit are rare, and can sometimes be difficult to
      characterize. Herniated orbital fat is thought to be a reactive process, but its
      presentation can mimic a lipomatous tumour such as an atypical lipomatous tumour
      or spindle cell/pleomorphic lipoma. Genetic studies to determine if it is indeed
      a reactive process rather than an adipocytic neoplasm have not been performed.
      METHODS AND RESULTS: Four samples of herniated orbital fat were reviewed
      clinically, histopathologically and immunohistochemically. Array comparative
      genomic hybridization (aCGH) was used to search for genome-wide copy number
      alterations within the tumours. Histological evaluation revealed that all four
      tumours contained collections of adipocytes surrounded by fibrous septae.
      Lochkern cells and floret-like multinucleated giant cells were present,
      consistent with herniated orbital fat. CD34 was positive in all tumours. Staining
      for MDM2 and CDK4 was negative. ACGH analysis demonstrated no copy number
      alterations. CONCLUSIONS: Herniated orbital fat may share some histopathological
      features with lipoma and atypical lipomatous tumour, but the absence of copy
      number gains or losses is consistent with the impression that herniated orbital
      fat is a reactive process. Genetic analysis may be another method to help
      differentiate herniated orbital fat from a lipomatous orbital tumour when the
      diagnosis is in question.

PMID- 24588546
TI  - Relax and refill: xylem rehydration prior to hydraulic measurements favours
      embolism repair in stems and generates artificially low PLC values.
AB  - Diurnal changes in percentage loss of hydraulic conductivity (PLC), with recorded
      values being higher at midday than on the following morning, have been
      interpreted as evidence for the occurrence of cycles of xylem conduits' embolism
      and repair. Recent reports have suggested that diurnal PLC changes might arise as
      a consequence of an experimental artefact, that is, air entry into xylem conduits
      upon cutting stems, even if under water, while under substantial tension
      generated by transpiration. Rehydration procedures prior to hydraulic
      measurements have been recommended to avoid this artefact. In the present study,
      we show that xylem rehydration prior to hydraulic measurements might favour xylem
      refilling and embolism repair, thus leading to PLC values erroneously lower than
      those actually experienced by transpiring plants. When xylem tension relaxation
      procedures were performed on stems where refilling mechanisms had been previously
      inhibited by mechanical (girdling) or chemical (orthovanadate) treatment, PLC
      values measured in stems cut under native tension were the same as those measured
      after sample rehydration/relaxation. Our data call for renewed attention to the
      procedures of sample collection in the field and transport to the laboratory, and
      suggest that girdling might be a recommendable treatment prior to sample
      collection for PLC measurements. 

PMID- 24588547
TI  - The marine diversity spectrum.
AB  - Distributions of species body sizes within a taxonomic group, for example,
      mammals, are widely studied and important because they help illuminate the
      evolutionary processes that produced these distributions. Distributions of the
      sizes of species within an assemblage delineated by geography instead of taxonomy
      (all the species in a region regardless of clade) are much less studied but are
      equally important and will illuminate a different set of ecological and
      evolutionary processes. We develop and test a mechanistic model of how diversity
      varies with body mass in marine ecosystems. The model predicts the form of the
      'diversity spectrum', which quantifies the distribution of species' asymptotic
      body masses, is a species analogue of the classic size spectrum of individuals,
      and which we have found to be a new and widely applicable description of
      diversity patterns. The marine diversity spectrum is predicted to be
      approximately linear across an asymptotic mass range spanning seven orders of
      magnitude. Slope -0.5 is predicted for the global marine diversity spectrum for
      all combined pelagic zones of continental shelf seas, and slopes for large
      regions are predicted to lie between -0.5 and -0.1. Slopes of -0.5 and -0.1
      represent markedly different communities: a slope of -0.5 depicts a 10-fold
      reduction in diversity for every 100-fold increase in asymptotic mass; a slope of
      -0.1 depicts a 1.6-fold reduction. Steeper slopes are predicted for larger or
      colder regions, meaning fewer large species per small species for such regions.
      Predictions were largely validated by a global empirical analysis. Results
      explain for the first time a new and widespread phenomenon of biodiversity.
      Results have implications for estimating numbers of species of small asymptotic
      mass, where taxonomic inventories are far from complete. Results show that the
      relationship between diversity and body mass can be explained from the dependence
      of predation behaviour, dispersal, and life history on body mass, and a neutral
      assumption about speciation and extinction.

PMID- 24588548
TI  - Evidence of the biochemical basis of host virulence in the greenbug aphid,
      Schizaphis graminum (Homoptera: Aphididae).
AB  - Biotypes of aphids and many other insect pests are defined based on the
      phenotypic response of host plants to the insect pest without considering their
      intrinsic characteristics and genotypes. Plant breeders have spent considerable
      effort developing aphid-resistant, small-grain varieties to limit insecticide
      control of the greenbug, Schizaphis graminum. However, new S. graminum biotypes
      frequently emerge that break resistance. Mechanisms of virulence on the aphid
      side of the plant-insect interaction are not well understood. S. graminum biotype
      H is highly virulent on most small grain varieties. This characteristic makes
      biotype H ideal for comparative proteomics to investigate the basis of biotype
      virulence in aphids. In this study, we used comparative proteomics to identify
      protein expression differences associated with virulence. Aphid proteins involved
      in the tricarboxylic acid cycle, immune system, cell division, and antiapoptosis
      pathways were found to be up-regulated in biotype H relative to other biotypes.
      Proteins from the bacterial endosymbiont of aphids were also differentially
      expressed in biotype H. Guided by the proteome results, we tested whether biotype
      H had a fitness advantage compared with other S. graminum biotypes and found that
      biotype H had a higher reproductive fitness as compared with two other biotypes
      on a range of different wheat germplasms. Finally, we tested whether aphid
      genetics can be used to further dissect the genetic mechanisms of biotype
      virulence in aphids. The genetic data showed that sexual reproduction is a source
      of biotypic variation observed in S. graminum. 

PMID- 24588549
TI  - Interaction between gastrocnemius muscle weakness and moderate exercise
      deteriorates joint integrity in rat knee.
AB  - The aim of this study was to determine the effect on the knee joint of the
      interaction between ankle muscle weakness and moderate exercise. Gastrocnemius
      muscle weakness was induced by intramuscular injection of botulinum toxin type A
      (BTX) in rats. Low-speed treadmill running (12 m/min for 60 min) was applied for
      6 weeks in rats with and without BTX. Untreated animals were used as controls.
      After BTX injection, the gastrocnemius muscle weakness was confirmed by 3-D
      motion analysis in kinematic features of the hindlimb during locomotion as an
      increased maximal dorsiflexion angle during the stance phase. Serum biomarker
      analysis by enzyme-linked immunosorbent assay revealed that low-speed running
      decreased the catabolic effect on type II collagen. However, the inhibition of
      catabolism induced by running exercise was significantly counteracted by BTX
      injection. In addition, thinning of the cartilage layer and a reduction in the
      chondrocyte density was also found in the tibial plateau of the knee in the BTX
      injected rats after running for 6 weeks. These data suggest that moderate
      exercise have a positive effect on joint homeostasis. However, ankle muscle
      weakness may alter the mechanical environment of the knee and impair the
      integrity of joint cartilage with moderate exercise.

PMID- 24588550
TI  - The impact on utilities of differences in body weight among Canadian patients
      with type 2 diabetes.
AB  - OBJECTIVE: The objective of this study was to estimate utility values for
      hypothetical health states that describe differences in weight and quality of
      life associated with type 2 diabetes mellitus (DM) from Canadians with type 2 DM.
      The impact on utility values was examined separately for participants with a body
      mass index (BMI) of 18 to less than 25 kg/m(2) ('healthy'), 25 to less than 30
      ('overweight'), and 30 or more ('obese'). METHODS: The health state descriptions
      were modified from a published diabetes utility study. Health states included a
      base-case type 2 DM health state (at participants' current weight), and six
      health states where the weight and attendant quality of life impact varied (base
      case +/-3%, +/-5%, and +/-7% weight). Utilities were elicited using the time
      trade-off technique. Linear regression modeling was used to estimate the utility
      increment or decrement associated with a one unit difference in BMI. RESULTS:
      Among 96 participants, the mean age was 55 years and 51% were men. The mean BMI
      was 32 kg/m(2) and 84% wanted to lose weight. The mean (SD) utility for the base
      case state was 0.911 (0.013). Mean utilities (utility decrements) were 0.907 (
      0.004), 0.865 (-0.046) and 0.806 (-0.105) for the health states describing an
      increased weight of 3%, 5% and 7%, respectively; and 0.923 (+0.012), 0.940
      (+0.029) and 0.949 (+0.038) for the health states describing a decreased weight
      of 3%, 5% and 7%, respectively. For every increase of 1 kg/m(2) BMI there was an
      associated decrease in utility of 0.0472 (95% CI: 0.0375, 0.0569) and for every
      decrease of 1 kg/m(2) BMI there was an associated increase in utility of 0.0171
      (95% CI: 0.0103, 0.0238). CONCLUSIONS: The preferences of Canadian patients with
      type 2 DM for diabetes-related health states varied according to the weight, and
      quality of life impact, associated with that health state. Increased weight had a
      greater effect on utilities than decreased weight.

PMID- 24588551
TI  - Mechanistic insights on the stereoselective nucleophilic 1,2-addition to sulfinyl
      imines.
AB  - The asymmetric nucleophilic 1,2-addition of (S)-N-benzylidene-2-methylpropane-2
      sulfinamide with methylmagnesium bromide and methyllithium has been investigated
      using DFT(B3LYP) computations. The calculated ratio of the two diastereomers
      agrees with experimental observations, and the factors that determine the
      diastereomeric ratio are discussed. The preference for the E isomer and the rapid
      equilibrium between the E and Z isomers of N-tert-butanesulfinyl imine are two
      key features for understanding the mechanism of this reaction. Methylmagnesium
      bromide and methyllithium have bifunctional roles, acting as both Lewis acid and
      nucleophile, and the Lewis acid character plays a determining role in the
      stereoselectivity of the reaction. 

PMID- 24588553
TI  - A retrospective examination of paleoparasitology and its establishment in the
      Journal of Parasitology.
AB  - Volume 95 (2009) of the Journal of Parasitology represented a significant
      benchmark in the history of paleoparasitology when it received on the cover
      formal recognition as a topical area for publication. This retrospective
      examination chronicles the emergence of paleoparasitology, from its origins as an
      adjunct contribution to the study of prehistoric human populations to its modern
      expression as a sub-disciplinary interest. The aim of paleoparasitology is to
      elucidate the temporal and spatial dimensions of parasitism from the fossil
      record of human and non-human host populations.

PMID- 24588552
TI  - Impact of contact lens zone geometry and ocular optics on bifocal retinal image
      quality.
AB  - PURPOSE: To examine the separate and combined influences of zone geometry, pupil
      size, diffraction, apodisation and spherical aberration on the optical
      performance of concentric zonal bifocals. METHODS: Zonal bifocal pupil functions
      representing eye + ophthalmic correction were defined by interleaving wavefronts
      from separate optical zones of the bifocal. A two-zone design (a central circular
      inner zone surrounded by an annular outer-zone which is bounded by the pupil) and
      a five-zone design (a central small circular zone surrounded by four concentric
      annuli) were configured with programmable zone geometry, wavefront phase and
      pupil transmission characteristics. Using computational methods, we examined the
      effects of diffraction, Stiles Crawford apodisation, pupil size and spherical
      aberration on optical transfer functions for different target distances. RESULTS:
      Apodisation alters the relative weighting of each zone, and thus the balance of
      near and distance optical quality. When spherical aberration is included, the
      effective distance correction, add power and image quality depend on zone
      geometry and Stiles Crawford Effect apodisation. When the outer zone width is
      narrow, diffraction limits the available image contrast when focused, but as
      pupil dilates and outer zone width increases, aberrations will limit the best
      achievable image quality. With two-zone designs, balancing near and distance
      image quality is not achieved with equal area inner and outer zones. With
      significant levels of spherical aberration, multi-zone designs effectively become
      multifocals. CONCLUSION: Wave optics and pupil varying ocular optics
      significantly affect the imaging capabilities of different optical zones of
      concentric bifocals. With two-zone bifocal designs, diffraction, pupil
      apodisation spherical aberration, and zone size influence both the effective add
      power and the pupil size required to balance near and distance image quality.
      Five-zone bifocal designs achieve a high degree of pupil size independence, and
      thus will provide more consistent performance as pupil size varies with light
      level and convergence amplitude.

PMID- 24588554
TI  - Metabolism of flavonoids in human: a comprehensive review.
AB  - Flavonoids are naturally occurring polyphenols, which are widely taken in diets,
      supplements and herbal medicines. Epidemiological studies have shown a flavonoid
      rich diet is associated with the decrease in incidence of a range of diseases.
      Pharmacological evidences also reveal flavonoids display anti-oxidant, anti
      allergic, anti-cancer, anti-inflammatory, anti-microbial and anti-diarrheal
      activities. Therefore, it is critical to study the biotransformation and
      disposition of flavonoids in human. This review summarizes the major metabolism
      pathways of flavonoids in human. First, lactase-phlorizin hydrolase (LPH) and
      human intestinal microflora mediate the hydrolysis of flavonoid glycosides, which
      is recognized as the first and determinant step in the absorption of flavonoids.
      Second, phase II metabolic enzymes (UGTs, SULTs and COMT) dominate the metabolism
      of flavonoids in vivo. UGTs are the most major contributors, followed by SULTs
      and COMT. By contrast, phase I metabolism pathway mediated by CYPs only plays a
      minor role. Third, the coupling of transporters (such as BCRP and MRPs) and phase
      II enzymes (UGTs and SULTs) plays an important role in the disposition of
      flavonoids, especially in the enteroenteric and enterohepatic circulations. Thus,
      all the above factors should be taken into consideration when studying
      pharmacokinetics of flavonoids. Here we describe a comprehensive metabolism
      profile of flavonoids, which will enhance our understanding of the mechanisms
      underlying the disposition and pharmacological effects of flavonoids in vivo. 

PMID- 24588555
TI  - If one plant toxin is harmful to livestock, what about two?
AB  - When livestock are poisoned by plants in a range setting, there is normally more
      than one poisonous plant in that area. Additionally, many plants contain more
      than one compound that is toxic to livestock. Frequently, much is known regarding
      the toxicity of the individual plants and their individual toxins; however,
      little is known regarding the effect of coexposure to multiple toxic plants or
      even the effect of multiple toxins from an individual plant. This review
      discusses some basic principles of mixture toxicology with a focus on recent
      research that examined the effect of co-administering multiple plant toxins from
      the same plant and the effect of co-administration of two different poisonous
      plants, each with different types of toxins. As combined intoxications are likely
      common, this information will be useful in further developing management
      recommendations for ranchers and in designing additional experiments to study the
      toxicity of multiple poisonous plants to livestock. 

PMID- 24588556
TI  - Evaluation of a novel trocar-site closure and comparison with a standard Carter
      Thomason closure device.
AB  - PURPOSE: The aim of this study was to evaluate and compare a novel trocars-site
      closure device, the WECK EFxTM Endo Fascial Closure System (EFx) with the Carter
      Thomason CloseSure System(r) (CT) for the closure of laparoscopic trocar site
      defects created by a 12-mm dilating trocar. METHODS: We created standardized
      laparoscopic trocars-site abdominal wall defects in cadaver models using a
      standard 12-mm laparoscopic dilating trocar. Trocar defects were closed in a
      randomized fashion using one of the two closure systems. We recorded time and
      number of attempts needed for complete defect closure. In addition, we recorded
      the ability to maintain pneumoperitoneum, endoscopic visualization, safety,
      security, and facility based on the surgeon's subjective evaluations. We compared
      outcomes for the EFx and CT closure systems. RESULTS: We created 72 standardized
      laparoscopic trocars-site abdominal wall defects. The mean time needed for
      complete defect closure was 98.53 seconds (+/-28.9) for the EFx compared with
      133.61 seconds (+/-54.61) for the CT (P<0.001). The mean number of attempts
      needed to achieve complete defect closure were 1.19 (1-3) for the EFx and 1.19 (1
      2) for the CT (P=0.50). Mean scores for safety were 2.92 for EFx vs 2.19 for CT
      (P<0.001). Mean scores for facility were 2.97 vs 1.83 for EFx and CT,
      respectively (P<0.001). Mean scores for maintenance of pneumoperitoneum were 1.97
      for EFx vs 2.33 for CT (P=0.022). No significant difference was observed between
      the EFx and the CT systems for endoscopic visualization (2.28 vs 2.50, P=0.080).
      CONCLUSIONS: In this in vitro cadaver trial, the EFx was superior in terms of
      time needed to complete defect closure, safety, and facility. CT was superior in
      terms of maintenance of pneumoperitoneum. Both systems were equal in the number
      of attempts needed to complete the defect closure and endoscopic visualization.

PMID- 24588557
TI  - Health related quality of life and perceptions of child vulnerability among
      parents of children with a history of Kawasaki disease.
AB  - AIM: Kawasaki disease (KD) is an acute paediatric vasculitis. The psychosocial
      consequences of this sudden illness for parents are unknown. This study aimed to
      evaluate health related quality of life (HRQOL) and parental perceptions of child
      vulnerability (PPCV) in parents of children with KD, and to identify variables
      associated with PPCV. METHODS: This cross-sectional study included 288 parents
      (83% mothers) of KD patients (mean age 8.7 years). HRQOL was assessed using the
      TNO-AZL Questionnaire for Adult's HRQOL (TAAQOL) and PPCV using the Child
      Vulnerability Scale (CVS). Scores of KD parents were compared with reference
      groups of Dutch parents. Logistic regression analyses were performed to examine
      associated variables. RESULTS: The HRQOL of KD parents was comparable to the
      HRQOL of parents of healthy children. However, KD parents showed significantly
      higher PPCV, regarding both the median CVS total score and the percentage in the
      clinical range. No differences were found in CVS outcomes between KD parents and
      parents of a chronically ill child. None of the studied parental, child and
      disease characteristics were significantly associated with PPCV. CONCLUSION:
      Parents perceived their KD child more vulnerable to illness than healthy
      children, while in reality the majority had fully recovered from KD.

PMID- 24588558
TI  - Identification by a proteomic approach of a plasma protein as a possible
      biomarker of illicit dexamethasone treatment in veal calves.
AB  - Corticosteroids have become the most widespread illegal growth promoters in veal
      calves and beef cattle. Testing for corticosteroids relies on either direct
      detection of compounds or their metabolites or indirect detection to identify
      changes in biological pathways. We used a comparative proteomic approach, based
      on two-dimensional electrophoresis (2DE), to identify plasma protein markers
      after short-term dexamethasone administration in veal calves. Twenty-three male
      Friesian veal calves were treated experimentally with dexamethasone sodium
      phosphate: 10 received low-dose administration of the drug (0.4 mg day-1 per os)
      for 20 consecutive days (treatment group); 10 received the drug at therapeutic
      dosage (2-4 mg kg-1 i.m.) for 3 consecutive days (comparison group). Three
      animals were not treated (control group). Plasma samples were collected from each
      animal at six time points (T1-T6; treatment and control group) and at four time
      points (T1-T4; comparison group) and stored at -80 degrees C until analysis.
      Plasma proteins were quantified and analysed in triplicate by 2DE. The images
      were analysed with Bionumerics(r) software. Comparison of 2DE maps obtained from
      blood samples at T1 (before treatment) and at T6 (final sampling) showed a
      significant disappearance (p < 0.001) of two protein spots at T6 in the treatment
      group. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis and
      immunoblotting identified these isoforms as serum paraoxonase/arylesterase 1
      precursor (PON1). Synthesised in the liver and released into the blood, PON1 has
      an important role in lipid metabolism. The absence of variation of this protein
      in the comparison group suggests that the marker has good specificity for
      detecting illicit corticosteroid treatment.

PMID- 24588559
TI  - Cannabinoids: clearing the smoke on pain, inflammation and neurodegeneration.
AB  - LINKED ARTICLES: This article is part of a themed section on Cannabinoids 2013.
      To view the other articles in this section, see Fagan and Campbell (2014) DOI:
      10.1111/bph.12492, Ignatowska-Jankowska et al. (2014) DOI: 10.1111/bph.12298,
      Ligresti et al. (2014) DOI: 10.1111/bph.12410, Lopez-Rodriguez et al. (2014) DOI:
      10.1111/bph.12519, Murataeva et al. (2014) DOI: 10.1111/bph.12411, Okine et al.
      (2014) DOI: 10.1111/bph.12540, Rodriguez-Cueto et al. (2014) DOI:
      10.1111/bph.12283, Stanley and O'Sullivan (2014) DOI: 10.1111/bph.12560, Toguri
      et al. (2014) DOI: 10.1111/bph.12545, Wu et al. (2014) DOI: 10.1111/bph.12500.
      Linked articles are: Avraham et al. (2014) DOI: 10.1111/bph.12478, Machado et al.
      (2014) DOI: 10.1111/bph.12488, Ward et al. (2014) DOI: 10.1111/bph.12439.

PMID- 24588560
TI  - Managed ventricular pacing below the lower rate limit during DDD to AAI
      transition: what is the mechanism?

PMID- 24588561
TI  - An exclusively human milk diet reduces necrotizing enterocolitis.
AB  - OBJECTIVE: This study tested the hypothesis that feeding an exclusively human
      milk (EHM) diet to premature infants reduces the incidence of necrotizing
      enterocolitis (NEC) associated with enteral feeding. STUDY DESIGN: An
      observational study for infants born at less than 33 weeks of gestational age was
      performed in a single neonatal intensive care unit. An EHM diet prospectively
      eliminated bovine-based artificial milk, including bovine-based fortifier,
      through 33 weeks postmenstrual age (PMA). The clinical data from a 2.5-year
      interval of the EHM diet were compared with data from the previous 6.5 years for
      similar infants who received bovine-based milk products before 33 weeks PMA.
      RESULTS: In the EHM diet cohort, 148 of 162 infants (91%) received EHM through 33
      weeks PMA. In order to achieve an EHM diet, 140 of 162 infants (86%) received
      their own mother's milk, and 98 of 162 infants (60%) received donor human milk.
      The EHM cohort was also fed a human milk-based fortifier to truly eliminate
      bovine products. The distribution of NEC onset in the EHM cohort was
      significantly different from that in the control cohort for the day of onset
      (p=0.042) and the PMA at onset (p=0.011). In the control cohort, NEC onset after
      Day 7 of life occurred in 15 of 443 infants (3.4%), significantly more than in
      the EHM cohort where NEC occurred in two of 199 infants (1%) (p=0.009).
      CONCLUSIONS: Changing to an EHM milk diet through 33 weeks PMA reduced the
      incidence of NEC associated with enteral feeding.

PMID- 24588562
TI  - Preparing disabled students for professional practice: managing risk through a
      principles-based approach.
AB  - AIM: A discussion exploring the ways disabled students are managed in practice
      settings. It proposes and argues for morally and legally viable principles to
      guide risk assessment and inclusive decision-making in practice. BACKGROUND:
      Equality law means that universities are bound not to discriminate against
      students on the basis, amongst other things, of disability. As a consequence in
      the UK, there is a perceived increase in numbers of disabled people applying for
      and succeeding as health professionals. Whilst placement providers are equally
      obliged by the law to have inclusive policies, competing needs including patient
      safety, public confidence and professional regulations mean that adjustments that
      can be made in an educational environment to appropriately support student
      learning may prove to be more difficult in placements that provide direct care to
      the public. DATA SOURCES: This discussion is an outcome of recommendations from
      published research by the authors and their research partners. It is supported by
      related literature, critical debate amongst academics, disabled students and
      disabled and non-disabled practitioners. IMPLICATIONS FOR NURSING: Ensuring a
      nursing workforce that mirrors the diversity of the population it serves is of
      universal importance. Effective management of disabled students can contribute to
      achieving this goal and to promoting a positive view of disabled practitioners.
      CONCLUSION: Legislation is necessary to protect disabled people from
      discrimination. To respect this legislation, when preparing nurses and other
      health professions, a clear understanding of the law and a principles-based
      approach to guiding risk is important.

PMID- 24588563
TI  - Quantitative label-free phosphoproteomics of six different life stages of the
      late blight pathogen Phytophthora infestans reveals abundant phosphorylation of
      members of the CRN effector family.
AB  - The oomycete Phytophthora infestans is the causal agent of late blight in potato
      and tomato. Since the underlying processes that govern pathogenicity and
      development in P. infestans are largely unknown, we have performed a large-scale
      phosphoproteomics study of six different P. infestans life stages. We have
      obtained quantitative data for 2922 phosphopeptides and compared their abundance.
      Life-stage-specific phosphopeptides include ATP-binding cassette transporters and
      a kinase that only occurs in appressoria. In an extended data set, we identified
      2179 phosphorylation sites and deduced 22 phosphomotifs. Several of the
      phosphomotifs matched consensus sequences of kinases that occur in P. infestans
      but not Arabidopsis. In addition, we detected tyrosine phosphopeptides that are
      potential targets of kinases resembling mammalian tyrosine kinases. Among the
      phosphorylated proteins are members of the RXLR and Crinkler effector families.
      The latter are phosphorylated in several life stages and at multiple positions,
      in sites that are conserved between different members of the Crinkler family.
      This indicates that proteins in the Crinkler family have functions beyond their
      putative role as (necrosis-inducing) effectors. This phosphoproteomics data will
      be instrumental for studies on oomycetes and host-oomycete interactions. The data
      sets have been deposited to ProteomeXchange (identifier PXD000433). 

PMID- 24588564
TI  - Chiral plasmonic films formed by gold nanorods and cellulose nanocrystals.
AB  - Chiral plasmonic films have been prepared by incorporating gold nanorods (NRs) in
      a macroscopic cholesteric film formed by self-assembled cellulose nanocrystals
      (CNCs). Composite NR-CNC films revealed strong plasmonic chiroptical activity,
      dependent on the photonic properties of the CNC host and plasmonic properties of
      the NRs. The plasmonic chiroptical properties of the composite films were tuned
      by changing the conditions of film preparation. The strategy presented herein
      paves the way for the scalable and cost-efficient preparation of plasmonic chiral
      materials. 

PMID- 24588565
TI  - Parenteral nutrition-associated bloodstream infection in an Australian teaching
      hospital--an 8-year retrospective study of over 11,000 PN-days.
AB  - BACKGROUND: Bloodstream infections (BSIs) are a well-recognized complication of
      parenteral nutrition (PN). However, their epidemiology and clinical consequences
      are incompletely described. METHODS: A retrospective cohort study was performed,
      from 2002 to 2009, of all hospital inpatients who were administered PN, outside
      the intensive care setting, at a major tertiary hospital in Queensland,
      Australia. RESULTS: In 780 episodes of PN administration, 120 BSIs occurred,
      giving an incidence of 10.0/1000 PN-days. The majority of PN-associated BSIs were
      classified as central line-associated (n = 98, 81.7%). Candida spp. were the most
      frequent pathogens. Observed BSI management revealed that over 8% of
      intravascular devices were inappropriately retained, over 30% of empirical
      antibiotic therapy was inappropriate, and 62% of antifungal therapy was delayed
      >= 48 h. All-cause hospital mortality was over 2-fold greater in patients with a
      PN-associated BSI compared to those without (17.9% vs 8.3%, crude odds ratio (OR)
      2.4, 95% confidence interval (CI) 1.29-4.35, p = 0.002). BSI was identified as an
      independent risk factor for mortality (adjusted OR 3.54, 95% CI 1.76-7.12, p <
      0.001). Low baseline albumin levels and a requirement for intravenous insulin
      infusion (a marker of sustained hyperglycaemia) were independent risk factors for
      the development of PN-associated BSIs. CONCLUSIONS: PN-associated BSI in hospital
      inpatients is common and is associated with mortality. The implementation of
      standardized evidence-based infection prevention strategies, particularly
      targeting IVD maintenance, is a priority. PN-associated BSI management pathways
      require optimization, with timely IVD removal and appropriate antimicrobial
      therapy. Depending on local epidemiology patterns, empirical antifungal therapy
      should be considered.

PMID- 24588566
TI  - Using Rh(III)-catalyzed C-H activation as a tool for the selective
      functionalization of ketone-containing molecules.
AB  - Due to the strong potential of C-H activation in many areas of organic chemistry,
      the use of a pre-existing carbonyl group for the installation of a directing
      group to enable selective and predictable alpha-alkenylation with activated
      olefins as coupling partners is described. This Heck-type reaction would then
      lead either to beta,gamma-unsaturated ketones or to variously substituted 1,4
      butadienes depending on the conditions used for the cleavage of the directing
      group. 

PMID- 24588567
TI  - Floral volatiles: from biosynthesis to function.
AB  - Floral volatiles have attracted humans' attention since antiquity and have since
      then permeated many aspects of our lives. Indeed, they are heavily used in
      perfumes, cosmetics, flavourings and medicinal applications. However, their
      primary function is to mediate ecological interactions between flowers and a
      diverse array of visitors, including pollinators, florivores and pathogens. As
      such, they ultimately ensure the plants' reproductive and evolutionary success.
      To date, over 1700 floral volatile organic compounds (VOCs) have been identified.
      Interestingly, they are derived from only a few biochemical networks, which
      include the terpenoid, phenylpropanoid/benzenoid and fatty acid biosynthetic
      pathways. These pathways are intricately regulated by endogenous and external
      factors to enable spatially and temporally controlled emission of floral
      volatiles, thereby fine-tuning the ecological interactions facilitated by floral
      volatiles. In this review, we will focus on describing the biosynthetic pathways
      leading to floral VOCs, the regulation of floral volatile emission, as well as
      biological functions of emitted volatiles. 

PMID- 24588568
TI  - Comparing unmet needs between community-based palliative care patients with heart
      failure and patients with cancer.
AB  - BACKGROUND: As the role of palliative care (PC) has yet to be clearly defined in
      patients with heart failure (HF), such patients may face barriers regarding PC
      referral. In order to maximally meet the needs of HF patients, it is necessary to
      understand how they compare to the classic PC population: patients with cancer.
      OBJECTIVE: To characterize the unresolved symptom and treatment needs with which
      patients with HF and those with cancer present to PC. METHODS: We used data from
      the Palliative Care Research Registry (PCRR), a repository of quality improvement
      data from three community-based PC organizations. We abstracted first PC visit
      data from the PCRR for patients with primary diagnoses of HF or cancer seen
      between 2008 and 2012. We assessed the association of primary diagnosis (i.e., HF
      or cancer) on three outcomes: unresolved symptoms, treatment gaps, and a
      composite indicator of symptom control and quality of life. Analyses included
      descriptive statistics and multivariate Poisson regression. RESULTS: Our analytic
      sample comprised 334 patients with HF and 697 patients with cancer, the majority
      of whom were white and male. Compared to patients with cancer, patients with HF
      presented with fewer unresolved symptoms, both overall and at moderate/severe
      distress levels. Patients with HF more commonly reported moderately/severely
      distressful dyspnea (25% versus 18%, p=0.02), and more commonly experienced
      dyspnea-related treatment gaps (17% versus 8%, p<0.001). CONCLUSIONS: Patients
      with HF possess care needs that are squarely within the purview of PC. Future
      work is needed to delineate how PC referral policies should be refined to
      optimize PC access for patients with HF.

PMID- 24588569
TI  - Octakis(tert-butoxo)dicerium(IV) [Ce2(O(t)Bu)8]: synthesis, characterization,
      decomposition, and reactivity.
AB  - An advanced synthesis for the homometallic derivative [Ce2(O(t)Bu)8] (1) starting
      from [Ce(O(t)Bu)2{N(SiMe3)2}2] was developed. Structural characterization of a
      cerium(IV) complex and its decomposition products confirmed the coexistence of
      both ether elimination and Ce-O bond cleavage processes, which lead to the
      formation of [Ce3O(O(t)Bu)10] and [Ce3(O(t)Bu)11] (2) derivatives, respectively.
      Variable-temperature NMR spectroscopy under strict exclusion of moisture enabled
      insight into the decomposition processes in noncoordinating solvents and at
      elevated temperature. In addition, structural analysis of the heterovalent 2 and
      of two new complexes of the general formula [Ce2(O(t)Bu)8(L)] [L = HO(t)Bu (3),
      OCPh2 (4)] is described. 

PMID- 24588570
TI  - Clarification of methods for hematologic reference intervals in adult alpacas.

PMID- 24588571
TI  - Combined assessment of serum free and total T4 in a general clinical setting
      seemingly has limited potential in improving diagnostic accuracy of thyroid
      dysfunction in dogs and cats.

PMID- 24588572
TI  - Chasing rainbows. Color reactions of analyses performed on a Siemens Dimension
      EXL.

PMID- 24588573
TI  - Hematologic and biochemical variables of hedgehogs (Erinaceus europaeus) after
      overwintering in rehabilitation centers.
AB  - BACKGROUND: Information about laboratory reference intervals (RIs) of European
      Hedgehog (Erinaceus europaeus) hospitalized at rehabilitation centers is scarce.
      OBJECTIVE: The purpose of this study was to establish hematologic and biochemical
      RIs for rehabilitated hedgehogs before the release into the wild, and to assess
      whether sex and management of the center influence laboratory results. METHODS:
      Blood was collected from 50 hedgehogs at 3 centers. Thirty-eight animals were
      included in the study based on normal body weight, absence of clinical signs of
      disease, Bunnell index > 0.80, and absence of hibernation during overwintering.
      CBCs were performed using an automated laser cell counter followed by morphologic
      analysis of blood smears. Clinical biochemistry was performed using an automated
      spectrophotometer. RIs were determined as recommended by the ASVCP guidelines.
      RESULTS: Hematology profiles revealed a prevalence of lymphocytes, a constant
      presence of nucleated RBCs, Howell-Jolly bodies and basophils, and bilobed nuclei
      in neutrophils and eosinophils. Biochemistry profiles were characterized by
      higher creatinine and urea concentrations, and higher ALP and GGT activities
      compared with other domestic species. The sex did not influence the results.
      Conversely, numbers of eosinophils, activated and large granular lymphocytes, and
      concentrations of total protein, glucose and cholesterol were different among the
      centers, likely due to different management practices (eg, antiparasitic
      treatments, environmental exposure to microorganisms, diet). CONCLUSION: The RIs
      established in this study can be used to monitor the health status of hedgehogs
      in rehabilitation centers. As management practices appeared to influence some
      variables, it is recommended to standardize the management protocols to minimize
      their influence on laboratory data.

PMID- 24588575
TI  - Detecting the simian immunodeficiency virus reservoir as viral DNA and RNA in
      situ simultaneously as a model to monitor viral latency.

PMID- 24588576
TI  - Entry of HIV in primary human resting CD4(+) T cells pretreated with the
      chemokine CCL19.

PMID- 24588577
TI  - Unraveling the gymnastics of reverse transcription through single molecule
      spectroscopy.

PMID- 24588578
TI  - Stable microtubule subsets facilitate early HIV-1 infection.

PMID- 24588579
TI  - Spelling Processes of Children With Nonsyndromic Cleft Lip and/or Palate: A
      Preliminary Study.
AB  - Objective :  To compare the cognitive-linguistic processes underlying spelling
      performance of children with cleft lip and/or palate with those of typically
      developing children. Design :  An assessment battery including tests of hearing,
      articulation, verbal short-term and working memory, and phonological awareness,
      as well as word and nonword spelling, was administered to both groups.
      Participants :  A total of 15 children with nonsyndromic cleft lip and/or palate
      were case-matched by age and sex to 15 typically developing children. The
      children were aged between 6 and 8 years and were bilingual, with English the
      dominant language. Results :  Wilcoxon signed-rank tests revealed that the
      performance of children with cleft lip and/or palate was significantly poorer on
      phoneme deletion and nonword spelling (P < .05) compared with typically
      developing children. Spearman correlation analyses revealed different
      relationships between the cognitive-linguistic and spelling measures for the
      cleft lip and/or palate and typically developing groups. Conclusions :  Children
      with cleft lip and/or palate underachieve in phonological awareness and spelling
      skills. To facilitate early intervention for literacy problems, speech-language
      pathologists should routinely assess the cognitive-linguistic processing of
      children with cleft lip and/or palate, especially phonological awareness, as part
      of their case management protocols. 

PMID- 24588580
TI  - The role of screening audiometry in the management of otitis media with effusion
      in children with cleft palate in northern ireland.
AB  - OBJECTIVE: To determine uptake and outcome of hearing screening in the cleft
      palate population in Northern Ireland (NI) and the rate of ventilation tube (VT)
      insertion over a 3-year period. DESIGN: In NI, hearing screening is offered in
      the neonatal period, at 9 months in the community, and at 2.5 years in the joint
      cleft clinic. Patients : Eighty-five children with cleft palate born between 2006
      and 2008 in NI were eligible for all three screenings. METHODS: A retrospective
      case note review was performed of tympanograms, audiometry, and VT insertion
      rates at each of the three time points. Results : In the neonatal period, all
      patients eligible were screened; 66 (77.6%) patients passed the screening, with
      19 patients (22.4%) failing, resulting in direct referral to ENT for
      consideration of VT. Results of the 9-month community screening were not made
      routinely available to the regional cleft service. At the 2.5-year clinic
      screening, all attending patients (n = 80) had documented screening. Fifty-two
      (65%) patients passed screening, with 28 patients (35%) failing screening. Forty
      six patients (57.5%) had documented VT, and 9 (11.25%) were awaiting ENT review
      for consideration of VT. CONCLUSION: Ventilation tubes are not routinely inserted
      at the time of cleft repair in the NI population, and 57.5% of our cleft
      population has ventilation tubes inserted by 2.5 years. Cleft patients in NI have
      regular routine hearing assessments, and our current practice avoids universal
      ventilation tube insertion while identifying those who need further hearing
      management. Further research is needed to reach an international consensus on the
      insertion of VT in cleft patients.

PMID- 24588581
TI  - Copper-catalyzed oxidative coupling of formamides with salicylaldehydes:
      synthesis of carbamates in the presence of a sensitive aldehyde group.
AB  - A diverse library of novel carbamates was synthesized utilizing copper-catalyzed
      oxidative C-O coupling of formamides and salicylaldehydes. Sensitive aldehyde
      groups remained intact in the presence of an oxidant and a transition-metal salt.
      Salicylaldehydes bearing electron-donating, electron-withdrawing, and halogen
      groups as well as 1-hydroxy-2-naphthaldehydes provided the desired carbamates in
      good to excellent yields. 

PMID- 24588582
TI  - Negative differential electrolyte resistance in a solid-state nanopore resulting
      from electroosmotic flow bistability.
AB  - A solid-state nanopore separating two aqueous solutions containing different
      concentrations of KCl is demonstrated to exhibit negative differential resistance
      (NDR) when a constant pressure is applied across the nanopore. NDR refers to a
      decrease in electrical current when the voltage applied across the nanopore is
      increased. NDR results from the interdependence of solution flow (electroosmotic
      and pressure-engendered) with the distributions of K+ and Cl- within the
      nanopore. A switch from a high-conductivity state to a low-conductivity state
      occurs over a very narrow voltage window (<2 mV) that depends on the nanopore
      geometry, electrolyte concentration, and nanopore surface charge density. Finite
      element simulations based on a simultaneous solution of the Navier-Stokes,
      Poisson, and Nernst-Planck equations demonstrate that NDR results from a positive
      feedback mechanism between the ion distributions and electroosmotic flow,
      yielding a true bistability in fluid flow and electrical current at a critical
      applied voltage, i.e., the NDR "switching potential". Solution pH and Ca2+ were
      separately employed as chemical stimuli to investigate the dependence of the NDR
      on the surface charge density. The NDR switching potential is remarkably
      sensitive to the surface charge density, and thus to pH and the presence of Ca2+,
      suggesting possible applications in chemical sensing.

PMID- 24588583
TI  - Prediction of time-to-attainment of recovery for borderline patients followed
      prospectively for 16 years.
AB  - OBJECTIVE: The purpose of this study was to determine the most clinically
      relevant baseline predictors of time-to-recovery from borderline personality
      disorder. METHOD: Two hundred and ninety in-patients meeting rigorous criteria
      for borderline personality disorder were assessed during their index admission
      using a series of semistructured interviews and self-report measures. Recovery
      status, which was defined as concurrent symptomatic remission and good social and
      full-time vocational functioning, was reassessed at eight contiguous 2-year time
      periods. Survival analytic methods (Cox regression), which controlled for overall
      baseline severity, were used to estimate hazard ratios and their confidence
      intervals. RESULTS: All told, 60% of the borderline patients studied achieved a 2
      year recovery. In bivariate analyses, seventeen variables were found to be
      significant predictors of earlier time-to-recovery. Six of these predictors
      remained significant in multivariate analyses: no prior psychiatric
      hospitalizations, higher IQ, good full-time vocational record in 2 years prior to
      index admission, absence of an anxious cluster personality disorder, high
      extraversion, and high agreeableness. CONCLUSION: Taken together, the results of
      this study suggest that prediction of time-to-recovery for borderline patients is
      multifactorial in nature, involving factors related to lack of chronicity,
      competence, and more adaptive aspects of temperament.

PMID- 24588585
TI  - The Indian Supreme Court's judgment in the case of Glivec((r)) - the uncertain
      future of pharmaceutical patents in India.

PMID- 24588586
TI  - Regulatory exclusivity in the EU: the impact of new active substance status.

PMID- 24588584
TI  - Conformational activation of poly(ADP-ribose) polymerase-1 upon DNA binding
      revealed by small-angle X-ray scattering.
AB  - Poly(ADP-ribose) polymerase-1 (PARP-1) is a nuclear protein that plays key roles
      in several fundamental cellular processes. PARP-1 catalyzes the polymerization of
      nicotinamide adenine dinucleotide on itself and other acceptor proteins, forming
      long branched poly(ADP-ribose) polymers. The catalytic activity of PARP-1 is
      stimulated upon binding to damaged DNA, but how this signal is transmitted from
      the N-terminal DNA binding domain to the C-terminal catalytic domain in the
      context of the full-length enzyme is unknown. In this paper, small-angle X-ray
      scattering experiments and molecular dynamics simulations were used to gain
      insight into the conformational changes that occur during the catalytic
      activation of PARP-1 by an 8-mer DNA ligand. The data are consistent with a model
      in which binding of the DNA ligand establishes interdomain interactions between
      the DNA binding and catalytic domains, which induces an allosteric change in the
      active site that promotes catalysis. Moreover, the PARP-1-8-mer complex is seen
      to adopt a conformation that is poised to recruit DNA repair factors to the site
      of DNA damage. This study provides the first structural information about the DNA
      induced conformational activation of full-length PARP-1. 

PMID- 24588587
TI  - Inter partes review: considerations for abbreviated new drug application cases.

PMID- 24588589
TI  - Changes in global pharmaceutical patent strategy due to intergovernmental
      cooperation.

PMID- 24588592
TI  - Crystalline forms of nonprotein drugs filed in Brazil from 1995-2005.
AB  - In the present study, we evaluated 457 patent applications filed for crystalline
      forms of nonprotein drugs during the period 1995-2005 in Brazil. Online searches
      were conducted using the Instituto Nacional da Propriedade Industrial patent
      database and the Derwent Innovations Index((r)). It was found that no patent
      applications in this area were filed by Brazilian applicants. It was also noted
      that only 61% of patent applications included the characterization of three or
      more crystalline phase techniques. In most applications, no determination of
      purity was provided for chemical and/or crystalline phases. In a subset of patent
      applications, those for blockbuster drugs, we found that approximately 90% did
      not meet Instituto Nacional da Propriedade Industrial acceptance criteria nor the
      criteria developed in this study. These results reveal that appropriate and
      thorough characterization of the crystalline forms of drugs is, indeed, lacking
      in patent applications. 

PMID- 24588593
TI  - Patenting personalized medicines in the UK, Europe and USA.
AB  - In this review, we take a look at the patentability issues surrounding
      personalized medicine patent claims. We examine how the USA and European Patent
      Office have dealt with such patent claims, and then review the UK 'inherency' and
      'selection' decisions to take a view as to how the UK courts will deal with
      personalized medicine patent claims in the future. We conclude that the UK courts
      will likely be willing to uphold patent protection for personalized medicines in
      the right circumstances. 

PMID- 24588594
TI  - Ca(2+) release-activated Ca(2+) channel inhibitors.
AB  - Ca(2+) release-activated Ca(2+) (CRAC) channels are becoming important targets
      for therapeutic intervention in several areas of disease, including immunology,
      allergy and cancer. In parallel to the progression towards reliable methods for
      measuring CRAC currents and their inhibition, patents have been generated by
      several companies. In this Patent Review, an analysis of the patents in the CRAC
      channel inhibition filed is presented. A discussion of the biological methods
      used in the patents is included. The general interest in this area is growing
      fast with almost 80% of the patents issued after 2010. 

PMID- 24588595
TI  - Tecfidera((r)): an approach for repurposing.
AB  - As a case study of patent coverage for a repurposed drug, Biogen Idec's approach
      for Tecfidera((r)), an oral formulation of dimethyl fumarate, was analyzed. While
      mixtures of fumarates have been used for over 50 years to treat psoriasis,
      Tecifidera is approved for the treatment of relapsing-remitting multiple
      sclerosis. Biogen pursued claims to pharmaceutical formulations and useful doses
      for treating multiple sclerosis, an approach that is relevant to pharmaceutical
      lifecycle management in general. A survey of recent US, EP, and PCT patent
      applications indicate other companies are developing competing fumarate
      formulations. While it is possible to pursue secondary patents for compounds
      without composition of matter coverage, regulatory data exclusivity provides
      additional protection to delay competitors. 

PMID- 24588596
TI  - Pharmaceutical and biomedical applications of lipid-based nanocarriers.
AB  - Increasing attention is being given to lipid nanocarriers (LNs) as drug delivery
      systems, due to the advantages offered of a higher biocompatibility and lower
      toxicity compared with polymeric nanoparticles. Many administration routes are
      being investigated for LNs, including topical, oral and parenteral ones. LNs are
      also proposed for specific applications such as cancer treatment, gene therapy,
      diagnosis and medical devices production. However, the high number of published
      research articles does not match an equal amount of patents. A recent Review of
      ours, published in Pharmaceutical Patent Analyst, reported the patents proposing
      novel methods for the production of LNs. This review work discusses recent
      patents, filed in 2007-2013 and dealing with the industrial applications of lipid
      based nanocarriers for the vectorization of therapeutically relevant molecules,
      as well as biotech products such as proteins, gene material and vaccines, in the
      pharmaceutical, diagnostic and biomedical areas. 

PMID- 24588597
TI  - Comment on "Toxicity and mutagenicity of Gulf of Mexico waters during and after
      the deepwater horizon oil spill".

PMID- 24588598
TI  - Histological and immunohistochemical studies of the structure of lymph nodes in
      Kilis goats.
AB  - Ten healthy adult Kilis goat mesenteric lymph nodes were used to examine the
      general structure of lymph nodes, lymphocytes, plasma cells, reticular cells and
      reticular fibers using histological methods. We also detected T lymphocytes using
      anti-CD3 [SP7], anti-CD4 [74-12-4], mouse anti-bovine CD4 [CC30] and mouse anti
      bovine CD8 [CC63] monoclonal antibodies (mAb); and B lymphocytes using anti-CD79a
      [HM57] mAb, macrophages using anti-macrophage [MAC387] mAb and follicular
      dendritic cells using anti-S100 polyclonal antibody (pAb). The distribution of
      these cells also was studied. Although the primer antibodies we used for CD3,
      CD8, CD79a, MAC387 and S100 worked well, the primer antibodies for CD4 were
      ineffective for paraffin embedded goat lymph nodes.

PMID- 24588599
TI  - PCR based detection of HPV 16 and 18 genotypes in normal oral mucosa of tobacco
      users and non-users.
AB  - There is increasing evidence of a causal association between human papillomavirus
      (HPV) and oral squamous cell carcinoma (OSCC). Several studies have shown that
      HPV is associated with increased risk of oral cancer independent of exposure to
      tobacco and alcohol. The association is valid for HPVs 16 and 18, which generally
      are considered high risk types, because they have been detected in oral
      dysplastic lesions and cancers. We determined the baseline prevalence of HPVs 16
      and 18 in normal oral mucosa of individuals with and without tobacco habit. PCR
      was used for DNA collected by oral smears to detect HPV 16/18 DNA in normal oral
      mucosa of 60 healthy individuals who were assigned to two groups of 30 subjects
      each. One group had a tobacco habit, the other did not. The tobacco user group
      comprised individuals who were tobacco chewers only. Sixty-five percent of
      individuals were positive for HPV 16/18 DNA, but HPV 16/18 positivity was less in
      individuals with tobacco habit than in those without tobacco habit. No
      significant association was found between the presence of HPVs and gender, age or
      duration of chewing habit, or between groups with and without a tobacco habit. We
      propose that HPVs16 and 18 commonly are present in normal oral mucosa and
      emphasize the importance of distinguishing clinical, subclinical and latent HPV
      infections when investigating HPVs and OSCC.

PMID- 24588600
TI  - Expression and localization of trefoil factor family genes in rat submandibular
      glands.
AB  - The trefoil factor (TFF) family, which comprises TFF1, TFF2 and TFF3, plays an
      essential role in epithelial regeneration within the gastrointestinal tract. All
      three TFFs are present in human saliva; TFF3 is the predominant trefoil peptide.
      Little is known about the expression and tissue distribution of TFFs in rats,
      which are commonly used as a model system for human studies. We investigated the
      localization of the TFF genes that encode secretory peptides in rat submandibular
      glands (SMG). All three TFFs were expressed in rat SMG, although their location
      varied. Substantial amounts of TFF1 were detected only in the cytoplasm of
      epithelial cells in the SMG granular convoluted tubules (GCT), while TFF2 and
      TFF3 were widely distributed in the cytoplasm of epithelial cells of intercalated
      ducts (ID), striated ducts (SD) and interlobular ducts (ILD). The three TFFs also
      were detected especially in the lumens of the SD and ILD. Semi-quantitative RT
      PCR and in situ hybridization experiments confirmed TFF1, TFF2 and TFF3 mRNA
      expressions in the SMG. Greater expression of TFF peptides and mRNA was observed
      in male rats than in females. The broad expression of TFFs in rat SMG cells and
      lumens suggests that TFFs function in this organ by their secretion into the duct
      lumens. We also found differences in TFF expression profiles between rat and
      human SMG; therefore, caution should be exercised when using rats as a model for
      human TFF studies.

PMID- 24588601
TI  - Association of serum uric acid and metabolic syndrome in type 2 diabetes.
AB  - AIM: The relationship between elevated serum uric acid level and metabolic
      syndrome (MS) has been debated. There is no data concerning this relation in
      Iranian population-based studies. The aim of this study was to determine the
      prevalence of hyperuricamia and its association with MS in type 2 diabetes
      mellitus (DM). PATIENTS AND METHODS: This was a cross- sectional study in 1978
      diabetic patients. Hyperuricamia was defined as uric acid >= 7 and >= 5.5 mg/dl
      for men and women respectively. Diagnosis of metabolic syndrome was based on
      ATPIII criteria. Clinical and biochemical parameters in hyperuricaemic and
      normouricaemic patients compared with other. RESULTS: The prevalence of
      hyperuricaemia and metabolic syndrome was 12.7% and 65.5% respectively. The
      prevalence of MS significantly increased in the highest quartile of uric acid
      levels compared with lowest quartile (74.4% vs 55.9%, p<0.001). Serum uric acid
      had positive association with cholesterol, triglyceride, non-HDL cholesterol and
      a negative association with fasting blood sugar (FBS), glycosylated hemoglobin
      (HbA1C) and HDL cholesterol. Possible independent biochemical predictors of
      hyperuricamia were cholesterol, triglyceride, creatnine and FBS. CONCLUSION: The
      prevalence of MS and its components increases with increasing levels of uric acid
      in type 2 diabetes. Regular assessment of uric acid could give information for
      predicting of MS and prevention of atherosclerosis in type 2 diabetes.

PMID- 24588602
TI  - Measurement equivalence of the language-brokering scale for Chinese American
      adolescents and their parents.
AB  - Language brokering occurs frequently in immigrant families. Using data from 279
      Chinese American families with adolescents who function as language brokers for
      their parents, the current study developed a comprehensive scale to assess
      adolescents' and their parents' perceptions of language brokering. Both versions,
      parent and adolescent, showed stable factor structures. We also examined
      measurement equivalence, including factorial and construct-validity invariance,
      for each subscale across parent gender, adolescent gender, adolescent nativity,
      and translation frequency. In general, metric factorial invariance was observed
      for most subscales across the different groups; these subscales can thus be used
      in future studies examining the relations between language brokering and other
      variables. Further, two adolescent subscales (i.e., adolescent-focused burden,
      positive relations with parents) and three parent subscales (i.e., parent-focused
      burden, negative feelings, positive relations with child) demonstrated strong
      factorial invariance consistently across different groups, and can thus be used
      in future studies examining mean group differences in language-brokering
      experiences. In terms of construct-validity equivalence, most subscales were
      associated with parent-child conflict and adolescent depressive symptoms to a
      similar degree across parent gender, adolescent gender, and nativity.
      Implications of the current findings and recommendations for future use are
      discussed.

PMID- 24588603
TI  - Depression and anger across 25 years: changing vulnerabilities in the VSA model.
AB  - Guided by the vulnerability-stress adaptation (VSA) model of marriage and a
      developmental systems perspective, the current study examined the association of
      mental health trajectories (depressive symptoms and expressed anger) across the
      transition to adulthood (ages 18 to 25) with perceived life stress in young
      adulthood (age 32) and adaptive interaction with a romantic partner and
      relationship risk at midlife (age 43), accounting for concurrent age 43 mental
      health. Data from a 25-year prospective, longitudinal study of 341 Canadians (178
      women and 163 men) show age 18 levels of both mental health variables predicted
      perceived life stress and intimate relationship outcomes. The slopes for
      expressed anger and depressive symptoms were associated with perceived life
      stress, and relationship risk was also predicted by the slope of expressed anger.
      Higher perceived life stress at age 32 was associated with less adaptive
      interaction and increased relationship risk at age 43. Evidence for mediating
      effects was also found. Implications for theory development, future research, and
      clinical intervention are discussed.

PMID- 24588604
TI  - What explains violated expectations of parent-child relationship in transition to
      parenthood?
AB  - Parent-child relationship is created already in prenatal fantasies and
      expectations of the child-to-be. Negative violation of these expectations after
      the child is born is known to be harmful for the parent-child relationship. Yet,
      research is scarce about the medical and psychological factors contributing to
      violated expectations (VE). This study models the role of parent-, delivery- and
      infant-related underlying mechanisms for VE. It further compares parents with
      assisted reproductive treatment (ART) and spontaneous conception (SC), and primi-
      and multiparous couples. The couples (n = 743) separately filled in
      questionnaires concerning their prenatal expectations (T1) and 2 months postnatal
      representations (T2) of intimacy and autonomy in the relationship with their
      child, measured with Subjective Family Picture Test. A negative or positive
      discrepancy indicated violated expectations. The parent-related (mental health
      and marital quality), delivery-related (maternal and paternal birth experience,
      unplanned Caesarean, and amount of analgesia) and infant-related (infant health
      problems, difficult infant characteristics, and parental worry) factors were
      assessed at T2. Results show that among mothers, the associations were mostly
      indirect and mediated via mental health problems. Among fathers, the associations
      were direct, marital problems most crucially predicting VE. ART fathers were less
      susceptible to VE resulting from infant-related problems than SC fathers, but
      more susceptible to VE resulting from delivery problems. Delivery- and infant
      related factors also predicted VE differently among primi- and multiparous
      mothers. Considering factors that contribute to VE is important when working with
      couples in transition to parenthood.

PMID- 24588605
TI  - Characteristics of mother-child conflict and child sex predicting resolution.
AB  - Data from 190 mothers and their 5- to 7-year-old children were used to evaluate
      how characteristics of mother-child conflict discussions contribute to the
      likelihood of reaching a compromise, a win-loss resolution, or a standoff. Dyads
      discussed 2 topics they reported having disagreements about that were emotionally
      arousing. Coders rated global measurements of mothers' emotional responsiveness,
      intrusiveness, and negativity; children's negativity; and the frequency of
      mothers' and children's constructive and oppositional comments. Child sex was
      examined as a moderator of the relation between discussion characteristics and
      resolution reached. Results indicated that more constructive comments by mothers
      and children increased the likelihood of reaching a resolution versus a standoff,
      but only children's constructive comments differentiated between a compromise and
      a win-loss resolution favoring mothers. Dyads with more emotionally responsive
      mothers who made fewer oppositional comments were also more likely to reach a
      compromise versus a win-loss resolution. A significant interaction with child sex
      revealed that, for boys, the use of more child oppositional comments was
      associated with a higher likelihood of reaching a standoff versus a compromise.
      Girls' oppositional comments did not predict resolution type. These results are
      discussed in terms of the children's developmental level and parents'
      socialization goals.

PMID- 24588606
TI  - Does adding an emotion component enhance the Triple P-Positive Parenting Program?
AB  - This pilot study aimed to compare the efficacy of a regular offering of the group
      delivered Triple P-Positive Parenting Program for child behavior problems with an
      enhanced version tailored to promote child emotion competence. Families of
      children between ages 3 and 6 years displaying early-onset conduct problems were
      randomly assigned to Group Triple P (GTP; final n = 18) or Emotion Enhanced
      Triple P (EETP; final n = 18), in which parents were encouraged to incorporate
      emotion labels and causes and to coach emotion competence during discussions of
      everyday emotional experiences with their child. Compared with parents who
      received GTP, parents who received EETP increased their discussion of emotion
      labels and emotion causes in conversations with their child at postintervention,
      but this advantage was lost by the 4-month follow-up. Parents in the EETP
      condition also used more emotion coaching postintervention and at follow-up.
      There were no differences at postintervention or follow-up in children's emotion
      knowledge skills. Postintervention improvement in disruptive child behavior was
      greater for GTP, but the groups converged at follow-up. Parents were similarly
      satisfied with both interventions. Overall, EETP showed little advantage over
      regular GTP delivery.

PMID- 24588607
TI  - The boundaries of optometric practice.

PMID- 24588608
TI  - Limited blinking could also be involved in watchmakers' glaucoma.

PMID- 24588609
TI  - Re: Leber's hereditary optic neuropathy masquerading as optic neuritis with
      spontaneous visual recovery.

PMID- 24588610
TI  - Response to Re: Blinking abnormalities in watchmaker's glaucoma pathogenesis.

PMID- 24588613
TI  - An ethnographic study of nurses' experience with nursing research and its
      integration in practice.
AB  - AIM: To report from a study aimed at illuminating how French Registered Nurses
      experience and engage in nursing research in clinical practice. BACKGROUND:
      Nursing research in France is mainly conducted by nurses working at clinical
      research units rather than by dedicated nurse researchers. Education, i.e.
      advanced degrees, in the field of nursing research is still in its infancy and
      not yet consistent with the international context. Outside France, the general
      perception is that nursing research is a unified part of professional nursing.
      Consequently, in-depth knowledge about how nurses in a French clinical context
      might experience and engage in nursing research is still lacking. DESIGN: The
      design of this study was influenced by an ethnographic approach as described by
      the French anthropologists Beaud and Weber. METHOD: Data, participatory
      observations, field notes and interviews (n = 6) were collected in a teaching
      hospital between April-August 2012. The field consisted of a wound-care unit and
      clinical research units. Collected data were analysed based on Beaud and Weber's
      description of analysis. RESULTS: Three beliefs were identified: being a unified
      part of a research team, being an integral part of 'crosswise - across'
      activities and being part of research activities. CONCLUSION/IMPLICATION FOR
      RESEARCH: Commitment to nursing research was strengthened by patient-related
      issues. Based on this context, nursing research would likely benefit from the
      support of a naturalized reciprocity between clinical practice and research.

PMID- 24588615
TI  - Cytostatic conditioning in experimental allogeneic bone marrow transplantation:
      Busulfan causes less early gastrointestinal toxicity but Treosulfan results in
      improved immune reconstitution.
AB  - BACKGROUND: Acute graft versus host disease (aGVHD) after allogeneic bone marrow
      transplantation (allo-BMT) is associated with significant morbidity and
      mortality. We evaluated the impact of the conditioning regimen on aGVHD comparing
      Treosulfan (Treo) and Busulfan (Bu) with total body irradiation (TBI). METHODS:
      Using a haploidentical murine model, B6D2F1 mice conditioned with Bu (100
      mg/kg)/Fludarabine (Flu, 500 mg/kg) or Treo (6000 mg/kg)/Flu (500 mg/kg) or TBI
      with 14 Gy received bone marrow cells and splenocytes (20 * 10(6)) from either
      syngeneic (B6D2F1) or allogeneic (C57BL/6N) donors in order to analyze aGVHD
      outcome. RESULTS: Conditioning with Bu/Flu or Treo/Flu resulted in significantly
      reduced aGVHD severity and improved survival (p < 0.05) after allo-BMT compared
      to TBI. On day 5 after allo-BMT, the organ damages of Bu/Flu conditioned animals
      were significantly reduced in association with diminished expression of tumor
      necrosis factor in serum compared to Treo/Flu. Interestingly, the early toxicity
      of Treo/Flu did not result in significantly higher aGVHD severity; furthermore, a
      significantly improved immune reconstitution of B220-positive B cells was
      observed at day 42 after Treo/Flu conditioning compared to Bu/Flu. CONCLUSION:
      Conditioning with Treo/Flu or Bu/Flu results in decreased aGVHD severity compared
      to TBI. Moreover, Treo/Flu was associated with improved immune reconstitution
      despite the early toxicity.

PMID- 24588614
TI  - Alanine analogues of [D-Trp]CJ-15,208: novel opioid activity profiles and
      prevention of drug- and stress-induced reinstatement of cocaine-seeking
      behaviour.
AB  - BACKGROUND AND PURPOSE: The novel macrocyclic peptide cyclo[Phe-D-Pro-Phe-D-Trp]
      ([D-Trp]CJ-15,208) exhibits kappa opioid (KOP) receptor antagonist activity in
      both in vitro and in vivo assays. The four alanine analogues of this peptide were
      synthesized and characterized both in vitro and in vivo to assess the
      contribution of different amino acid residues to the activity of [D-Trp]CJ
      15,208. EXPERIMENTAL APPROACH: The peptides were synthesized by a combination of
      solid phase peptide synthesis and cyclization in solution. The analogues were
      evaluated in vitro in receptor binding and functional assays, and in vivo with
      mice using a tail-withdrawal assay for antinociceptive and opioid antagonist
      activity. Mice demonstrating extinction of cocaine conditioned-place preference
      (CPP) were pretreated with selected analogues to evaluate prevention of stress or
      cocaine-induced reinstatement of CPP. KEY RESULTS: The alanine analogues
      displayed pharmacological profiles in vivo distinctly different from [D-Trp]CJ
      15,208. While the analogues exhibited varying opioid receptor affinities and
      kappa and MU opioid receptor antagonist activity in vitro, they produced potent
      opioid receptor-mediated antinociception (ED50 = 0.28-4.19 nmol, i.c.v.) in vivo.
      Three of the analogues also displayed KOP receptor antagonist activity in vivo.
      Pretreatment with an analogue exhibiting both KOP receptor agonist and antagonist
      activity in vivo prevented both cocaine- and stress-induced reinstatement of
      cocaine-seeking behaviour in the CPP assay in a time-dependent manner.
      CONCLUSIONS AND IMPLICATIONS: These unusual macrocyclic peptides exhibit in vivo
      opioid activity profiles different from the parent compound and represent novel
      compounds for potential development as therapeutics for drug abuse and possibly
      as analgesics.

PMID- 24588616
TI  - In vitro immunomodulatory effects of 5-amino-3-methyl-4-isoxazolecarboxylic acid
      hydrazide on the cellular immune response.
AB  - The aim of this study was to determine the immunomodulatory activity of 5-amino-3
      methyl-4-isoxazolecarboxylic acid hydrazide in vitro. This compound was used for
      the synthesis of a series of 5-amino-3-methyl-4-isoxazolecarboxylic acid
      semicarbazides and thiosemicarbazides with documented immunotropic activity. The
      performed measurements assessed the cytotoxic effect of 5-amino-3-methyl-4
      isoxazolecarboxylic acid hydrazide on the murine macrophages (cell line J774E.1)
      and lymphoblasts (cell line D10.G4.1), the influence of this compound on the
      proliferation of murine lymphocytes isolated from peripheral lymphatic organs and
      murine peritoneal macrophages stimulated with mitogens (concanavalin A(ConA),
      lipopolysaccharide (LPS), phytohemagglutinin A (PHA)). Moreover, the production
      of tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta by the murine
      peritoneal macrophages stimulated with LPS from Escherichia coli was assessed. It
      was found that 5-amino-3-methyl-4-isoxazolecarboxylic acid hydrazide displayed no
      cytotoxic effects in the murine J774E.1 and D10.G4.1 cell lines in a wide range
      of concentrations (0.5-200 MUg/ml). Furthermore, the compound stimulated
      proliferation of lymphocytes isolated from the spleen and mesenteric lymph nodes
      when used alone and in combination with mitogens (ConA and PHA). This effect was
      stronger in the nonstimulated cells, and it followed a dose-response
      relationship. The same phenomenon was observed for the proliferation of the
      murine peritoneal macrophages. The investigated hydrazide, at the highest used
      concentration of 150 MUg/ml, increased the LPS-induced production of IL-1beta and
      did not affect the level of TNF-alpha. These results confirmed the
      immunomodulatory properties of 5-amino-3-methyl-4-isoxazolecarboxylic acid
      hydrazide and indicated that this compound could be useful in further research
      aimed at finding novel functional drugs.

PMID- 24588617
TI  - Forced to align: flow-induced long-range alignment of hierarchical molecular
      assemblies from 2D to 3D.
AB  - Nanostructured molecular thin films adsorbed on solid surfaces form the basis of
      numerous applications. Long-range order within adsorbed molecules is very often a
      desirable property for such systems. In this contribution, we report a simple and
      efficient method to fabricate well-aligned thin films of organic molecules over a
      few millimeter squares. The strategy involves use of capillary force in a two
      step flow method to induce large-area alignment of multilayers of molecules at
      the organic liquid-solid interface. Furthermore, we also demonstrate the
      influence of alignment on the electron transport through these well-aligned thin
      films using scanning tunneling spectroscopy. 

PMID- 24588618
TI  - Quantitation of physiological and biochemical barriers to siRNA liver delivery
      via lipid nanoparticle platform.
AB  - Effective delivery of small interfering RNA (siRNA) requires efficient cellular
      uptake and release into cytosol where it forms an active complex with RNAi
      induced silencing complex (RISC). Despite rapid developments in RNAi
      therapeutics, improvements in delivery efficiency of siRNA are needed to realize
      the full potential of this modality in broad therapeutic applications. We
      evaluated potential physiological and biochemical barrier(s) to the effective
      liver delivery of siRNA formulated in lipid nanoparticle (LNP) delivery vehicles.
      The comparative siRNA delivery performance of three LNPs was investigated in
      rats. They were assembled with either C14- or C18-anchored PEG-lipid(s), cationic
      lipid(s), and various helper lipid(s) and contained the same siRNA duplex. These
      LNPs demonstrated differentiated potency with ED50's ranging from 0.02 to 0.25
      mg/kg. The two C14-PEG-LNPs had comparable siRNA exposure in plasma and liver,
      while the C18-PEG-LNP demonstrated a higher plasma siRNA exposure and a slower
      but sustained liver uptake. RISC bound siRNA within the liver, a more proximal
      measure of the pharmacologically active siRNA species, displayed loading kinetics
      that paralleled the target mRNA knockdown profile, with greater RISC loading
      associated with more potent LNPs. Liver perfusion and hepatocyte isolation
      experiments were performed following treatment of rats with LNPs containing
      VivoTag-fluorescently labeled siRNA. One hour after dosing a majority of the
      siRNA within the liver was associated with hepatocytes and was internalized
      (within small subcellular vesicles) with no significant cell surface association,
      indicating good liver tissue penetration, hepatocellular distribution, and
      internalization. Comparison of siRNA amounts in hepatocytes and subcellular
      fractions of the three LNPs suggests that endosomal escape is a significant
      barrier to siRNA delivery where cationic lipid seems to have a great impact.
      Quantitation of Ago-2 associated siRNA revealed that after endosomal escape
      further loss of siRNA occurs prior to RISC loading. This quantitative assessment
      of LNP-mediated siRNA delivery has highlighted potential barriers with respect to
      endosomal escape and incomplete RISC loading for delivery optimization efforts. 

PMID- 24588619
TI  - Dietary exposure assessment of Spanish citizens to hexabromocyclododecane through
      the diet.
AB  - A study was performed to assess exposure of the Spanish population to
      hexabromocyclododecane (HBCD). Based on consumption data statistics, food items
      from six food groups, i.e., fish and seafood, meat, animal fat, dairy products,
      eggs, and vegetable oils, were sampled and analyzed for HBCD followed by per
      capita intake calculations. The highest levels of HBCD were found in the fish and
      seafood samples (mean value of 11.6 ng/g lw), followed by meat samples (mean
      value of 2.68 ng/g lw), eggs (mean value of 1.75 ng/g lw), dairy products (mean
      value of 0.78 ng/g lw), animal fat (mean value of 0.74 ng/g lw), and vegetable
      oils (mean value of 0.45 ng/g lw). The daily ingestion rate of HBCD was estimated
      at 2.58 ng (kg of body weight)(-1) day(-1). HBCD mainly came from fish and
      seafood (56%), but also dairy products (14%) and meat (12%) contributed. 

PMID- 24588620
TI  - Phase separation of a hexacyanoferrate-bridged coordination framework under
      electrochemical na-ion insertion.
AB  - Phase separation and transformation induced by electrochemical ion insertion are
      key processes in achieving efficient energy storage. Exploration of novel
      insertion electrode materials/reactions is particularly important to unravel the
      atomic/molecular-level mechanism and improve the electrochemical properties.
      Here, we report the unconventional phase separation of a cyanide-bridged
      coordination polymer, Eu[Fe(CN)6].4H2O, under electrochemical Na-ion insertion.
      Detailed structural analyses performed during the electrochemical reaction
      revealed that, in contrast to conventional electrochemical phase separation
      induced by the elastic interaction between nearest neighbors, the phase
      separation of NaxEu[Fe(CN)6].4H2O is due to a long-range interaction, namely,
      cooperative rotation ordering of hexacyanoferrates. Kolmogorov-Johnson-Mehl
      Avrami analysis showed that the activation energy for the phase boundary
      migration in NaxEu[Fe(CN)6].4H2O is lower than that in other conventional
      electrode materials such as Li(1-x)FePO4.

PMID- 24588621
TI  - Determination of the aflatoxin AFB1 from corn by direct analysis in real time
      mass spectrometry (DART-MS).
AB  - Direct analysis in real time (DART) ionisation coupled to a high-resolution mass
      spectrometer (MS) was used for screening of aflatoxins from a variety of surfaces
      and the rapid quantitative analysis of a common form of aflatoxin, AFB1,
      extracted from corn. Sample preparation procedure and instrument parameter
      settings were optimised to obtain sensitive and accurate determination of
      aflatoxin AFB1. 84:16 acetonitrile water extracts of corn were analysed by DART
      MS. The lowest calibration level (LCL) for aflatoxin AFB1 was 4 MUg kg-1.
      Quantitative analysis was performed with the use of matrix-matched standards
      employing the 13C-labelled internal standard for AFB1. DART-MS of spiked corn
      extracts gave linear response in the range 4-1000 MUg kg-1. Good recoveries (94
      110%) and repeatabilities (RSD = 0.7-6.9%) were obtained at spiking levels of 20
      and 100 MUg kg-1 with the use of an isotope dilution technique. Trueness of data
      obtained for AFB1 in maize by DART-MS was demonstrated by analysis of corn
      certified reference materials.

PMID- 24588622
TI  - Analytical performance of a dry chemistry analyzer designed for in-clinic use.
AB  - BACKGROUND: The Heska Dri-Chem 4000 uses dry slide technology to evaluate serum
      or plasma. No previous independent performance evaluation is published to the
      authors' knowledge. OBJECTIVES: The objectives were to (1) characterize
      analytical performance of a Dri-Chem 4000 by measuring precision and bias, (2)
      compare analytical performance of that Dri-Chem 4000 unit with a predetermined
      quality requirement, and (3) determine whether statistical QC of the Dri-Chem
      4000 is possible using the 13s control rule. METHODS: Sixteen analytes were
      measured using plasma from dogs, cats, and horses. Coefficient of variation (CV),
      bias, and observed total error (TEobs ) were calculated. TEobs was compared with
      allowable total error (TEa ). Sigma metric and quality goal index were calculated
      where relevant. QC validation was performed. RESULTS: Bias and TEobs calculated
      using quality control material (QCM) data were smaller than those calculated
      using method comparison data. Using TEobs calculated from species-specific CV and
      QCM-based bias, 100% of analytes in each species met ASVCP-recommended TEa .
      Desired error detection and false rejection rates were achievable using the 13s
      control rule and ASVCP-recommended TEa values for 9/16 (56%) of analytes in dogs,
      9/14 (64%) of analytes in cats, and 8/13 (62%) of analytes in horses.
      CONCLUSIONS: Analytical performance of the Dri-Chem 4000 is comparable to that
      reported by other authors for other small benchtop biochemistry analyzers.
      Statistical QC using a simple control rule is possible for most analytes in dogs,
      cats, and horses.

PMID- 24588623
TI  - Alternative sites for right ventricular pacing in Chagas disease: a comparative
      study of the mid-septum and inflow tract.
AB  - BACKGROUND: The right ventricular mid-septum and inflow tract are alternative
      pacing sites that are potentially less harmful to cardiac function. OBJECTIVE:
      This study aimed to analyze the influence of these two alternative pacing sites
      on the clinical course of patients with chronic Chagas disease, who underwent
      definitive pacemaker implantation. METHODS: A total of 80 patients with Chagas
      disease and classical indications for definitive pacemaker implantation were
      randomized into two groups between October 2008 and August 2010: 40 received
      inflow tract implantation and 40 patients received mid-septum implantation. The
      analyzed parameters included: (1) progression stage of chronic chagasic
      cardiomyopathy (CCC), (2) electrocardiographic analysis, (3) left ventricular
      remodeling, and (4) electromechanical dyssynchrony. The assessment was performed
      24-48 hours after implantation and a follow-up period of 18 months. RESULTS:
      Compared with inflow tract implantation, mid-septum implantation was associated
      with slower CCC progression and the generation of narrower QRS complexes (131.8
      +/- 8.4 milliseconds vs 150.5 +/- 10.5 milliseconds; P < 0.01). No left
      ventricular remodeling was detected. Intraventricular dyssynchrony was more
      frequent in the inflow tract group than in the mid-septum group (85% vs 32.5%,
      respectively; odds ratio [OR], 9.15; P = 0.02) as was interventricular
      dyssynchrony (37.5% vs 17.5%, respectively; OR, 2.83; P < 0.01). CONCLUSIONS: Mid
      septum implantation was associated with slower CCC progression, generation of
      narrower QRS complexes, and lower electromechanical dyssynchrony, suggesting that
      this pacing site could be less harmful to cardiac function than the inflow tract
      site in patients with CCC.

PMID- 24588624
TI  - iTRAQ protein profile analysis of tomato green-ripe mutant reveals new aspects
      critical for fruit ripening.
AB  - Green-ripe (Gr) tomato carries a dominant mutation and yields a nonripening fruit
      phenotype. The mutation results from a 334 bp deletion in a gene of unknown
      function at the Gr locus. The putative influence of Gr gene-deletion mutation on
      biochemical changes underlying the nonripening phenotype remains largely unknown.
      Respiration of Gr fruit was found to be reduced at mature green and breaker stage
      of ripening, while the fruit softening was dramatically prolonged. We studied the
      proteome of Gr mutant fruit using high-throughput iTRAQ and high-resolution mass
      spectrometry and identified 43 proteins representing 43 individual genes as
      potential influence-targets of Gr mutated fruit. The identified proteins are
      involved in several ripening-related pathways including cell-wall metabolism,
      photosynthesis, oxidative phosphorylation, carbohydrate and fatty acid
      metabolism, protein synthesis, and processing. Affected protein levels are
      correlated with the corresponding gene transcript levels. The modulation in the
      accumulation levels of PI(U1)P, PGIP, and PG2 supported the delayed softening
      phenotype of the Gr fruit. Further investigation in GR gene-silencing fruit
      ascertained the doubtless modulation of these targets by the deletion mutation of
      GR gene. 

PMID- 24588625
TI  - Asymmetric design of bipolar host materials with novel 1,2,4-oxadiazole unit in
      blue phosphorescent device.
AB  - The intrinsic asymmetry of 1,2,4-oxadiazole was utilized to synthesize three
      isomers, DCzmOXD-1, DCzmOXD-2, and mCzmOXD, and high triplet energies over 2.80
      eV made them good candidates for host materials in blue OLEDs. The best
      efficiencies of 23.0 cd A(-1)/20.5 lm W(1-)/11.2% in CE/PE/EQE were achieved by
      DCzmOXD-1 with derivation at the beta-carbon position of 1,2,4-oxadiazole. 

PMID- 24588626
TI  - When open-ended questions don't work: the role of palliative paternalism in
      difficult medical decisions.
AB  - Abstract The balance between patient autonomy and medical paternalism must be
      reexamined. The tension between autonomy and paternalism is both an ethical and
      practical issue. Autonomy is the current gold standard approach to patient
      communication and has grown to the point that patient preference dictates care,
      even when their choices are not possible or are medically nonbeneficial.
      Furthermore, we have observed a trend among physicians to avoid making difficult
      medical decisions by hiding behind a shield of patient autonomy. Paternalism,
      characterized as the antithesis of autonomy, is widely dismissed as having any
      role in medicine. We disagree and believe that paternalism still has an important
      role in medical decision making. 

PMID- 24588627
TI  - The P450 system and mTORC1 signalling in acne.
AB  - In this issue, Hellmann-Regen et al. suggested that anti-acne effects of
      erythromycin and tetracyclines may be related to their inhibitory effect of
      cytochrome P450-mediated degradation of all-trans-retinoic acid (ATRA). We have
      recently proposed that all anti-acne agents function by attenuation of increased
      mTORC1 signalling. This commentary links the P450 system to mTORC1 regulation in
      acne. Drug-mediated induction of P450 activity or P450 mutants with increased
      catabolic activity may reduce cellular ATRA levels and FoxO1 expression, thus
      reducing FoxO-mediated mTORC1 inhibition. In contrast, agents blocking ATRA
      degradation such as erythromycin and tetracyclines may improve acne by increasing
      FoxO1 expression with consecutive inhibition of mTORC1 signalling. 

PMID- 24588628
TI  - Childhood sleep duration and lifelong mortality risk.
AB  - OBJECTIVE: Sleep duration is known to significantly affect health in adults and
      children, but little is understood about long-term associations. This prospective
      cohort study is the first to examine whether childhood sleep duration is
      associated with lifelong mortality risk. METHOD: Data from childhood were refined
      and mortality data collected for 1,145 participants from the Terman Life Cycle
      Study. Participants were born between 1904 and 1915, lived to at least 1940, and
      had complete age, bedtime, and waketime data at initial data collection (1917
      1926). Homogeneity of the cohort sample (intelligent, mostly White) limits
      generality but provides natural control of common confounds. Through 2009, 1,039
      participants had confirmed deaths. Sleep duration was calculated as the
      difference between each child's bed and wake times. Age-adjusted sleep (deviation
      from that predicted by age) was computed. Cox proportional hazards survival
      models evaluated childhood sleep duration as a predictor of mortality separately
      by sex, controlling for baseline age. RESULTS: For males, a quadratic relation
      emerged: Male children who underslept or overslept compared with peers were at
      increased risk of lifelong all-cause mortality (HR = 1.15, CIs [1.05, 1.27]).
      Effect sizes were smaller and nonsignificant in females (HR = 1.02, CIs [0.91,
      1.14]). CONCLUSIONS: Male children with shorter or longer sleep durations than
      expected for their age were at increased risk of death at any given age in
      adulthood. The findings suggest that sleep may be a core biobehavioral trait,
      with implications for new models of sleep and health throughout the entire life
      span.

PMID- 24588629
TI  - Precancer risk perceptions predict postcancer subjective well-being.
AB  - OBJECTIVE: The present study used longitudinal data to explore whether subjective
      well-being in cancer survivors was related to predisease judgments of their
      likelihood of getting cancer. METHOD: Subjective well-being was assessed in terms
      of affective well-being (frequency of positive and negative affective states) and
      satisfaction with one's life overall. The sample consisted of 158 participants in
      the National Survey of Midlife Development in the U.S. (MIDUS) who developed
      cancer during the 8-10 years between the first and second waves of the survey
      (average time since diagnosis = 3.37 years; SD = 2.48), and 3,243 control
      participants who reported no history of cancer at either wave. RESULTS:
      Controlling for demographic variables and well-being at Wave 1, the effect of
      cancer on well-being depended on whether, prior to being diagnosed, people judged
      themselves to be at low or high risk of cancer. For those perceiving a high risk,
      a cancer diagnosis had a modest but significant negative impact on affect and
      life satisfaction, whereas no negative impact emerged for those perceiving a low
      risk. Similar effects were not observed for heart attack risk perceptions, or for
      measures of trait optimism or depression, suggesting that the effect was domain
      specific. CONCLUSIONS: Low precancer risk perceptions were associated with long
      term benefits for subjective well-being in people who developed cancer.

PMID- 24588631
TI  - Prevention moderates associations between family risks and youth catecholamine
      levels.
AB  - OBJECTIVE: The purpose of this study was to establish, using a quasi-experimental
      design, whether 2 family risk factors, parental psychological dysfunction and
      nonsupportive parenting, during preadolescence could longitudinally predict
      elevated sympathetic nervous system (SNS) activity 9 years later, and to
      determine whether participation in an efficacious family centered prevention
      program could moderate these associations if they emerged. METHOD: Rural African
      American preadolescents (N = 476) were assigned randomly to the Strong African
      American Families (SAAF) program or to a control condition. When youths were 11
      years of age (M = 11.2 years), primary caregivers provided data on their own
      depressive symptoms and self-esteem, and youths provided data on their receipt of
      nonsupportive parenting. When the youths were 20 years of age, indicators of SNS
      activity, the catecholamines epinephrine and norepinephrine, were assayed from
      their overnight urine voids. RESULTS: Parental psychological dysfunction and
      nonsupportive parenting forecast elevated catecholamine levels for youths in the
      control condition, but not for those in the SAAF condition. CONCLUSIONS: The
      demonstration that a prevention program can induce reduction of catecholamine
      levels is important from both theoretical and public health perspectives, because
      it shows that the developmental progression from family risk factors to
      heightened sympathetic nervous system activity is not immutable.

PMID- 24588630
TI  - Chronic weight dissatisfaction predicts type 2 diabetes risk: aerobic center
      longitudinal study.
AB  - OBJECTIVE: Weight dissatisfaction, defined as discordance between actual and goal
      weight, may be associated with increased risk for several obesity-related
      comorbidities. The purpose of the study was to examine the association between
      weight dissatisfaction and risk of developing Type 2 diabetes. METHOD: This
      longitudinal study used data from 9,584 adults enrolled in the Aerobics Center
      Longitudinal Study. Key variables included multiple measures of measured weight,
      self-reported goal weight, and incident diabetes. Weight dissatisfaction was
      defined as being above the median of measured weight minus goal weight. Cox
      proportional hazards regression estimated hazard ratios (HRs) and 95% confidence
      intervals (CIs) for diabetes incidence by weight dissatisfaction. RESULTS: HRs
      for time until diabetes diagnosis revealed that family history of diabetes (HR =
      1.46, 95% CI [1.13, 1.90]), age (HR = 1.03, 95% CI [1.02, 1.04]), and weight
      dissatisfaction (HR = 1.83, 95% CI [1.50, 2.25]) at baseline were statistically
      significant predictors. Longitudinally, higher risk was observed in individuals
      who either stayed dissatisfied (HR = 2.98, 95% CI [1.98, 4.48]) or became
      dissatisfied (HR = 1.51, 95% CI [0.79, 2.89]), compared with those who stayed
      satisfied. After additional adjustment for BMI, the elevated HR for those who
      remained dissatisfied compared with those who remained satisfied persisted (HR =
      2.85, 95% CI [1.89, 4.31]). CONCLUSIONS: Weight dissatisfaction, regardless of
      BMI, represents a potentially important psychophysiological modifier of the
      relationships between BMI and risk of Type 2 diabetes, and warrants greater
      attention in future studies of chronic disease risk.

PMID- 24588632
TI  - What parents and their adolescent sons suggest for male HPV vaccine messaging.
AB  - OBJECTIVE: The purpose of this article was to identify the information parents
      and their adolescent sons deem important when making the decision to get
      vaccinated against human papillomavirus (HPV). METHOD: Twenty-one adolescent
      males (ages 13 to 17), with no previous HPV vaccination, and their parents were
      recruited from adolescent primary care clinics serving low- to middle-income
      families in a large Midwestern city. Dyad members participated in separate
      semistructured interviews eliciting the information participants felt would
      increase vaccine uptake and series completion via media and clinic-based sources.
      Interviews were recorded, transcribed, and coded using inductive content
      analysis. RESULTS: Overall, participants felt fear-based messages would be most
      effective for increasing vaccination uptake through commercials. When describing
      clinic messages, parents and sons felt the most important component was a
      recommendation for vaccination from the health care provider (HCP). Additionally,
      parents desired more information about the vaccine from the HCP than the sons,
      including cost, number of shots, and time since the approval of the vaccine for
      males. Compared with the clinic message, the commercial message was a vector for
      vaccine awareness, whereas the clinic message was a source of vaccine
      information. Vaccine initiation messages should provide vaccine information and
      come from an HCP, whereas completion messages should remind the patient why they
      initiated the vaccine and can come from any medical staff. CONCLUSIONS:
      Family/individual-focused interventions should be tailored to message source,
      timing, and target audience. This information can be used to guide public health
      professionals in the development of interventions to increase vaccine uptake.

PMID- 24588633
TI  - Family disruption increases functional somatic symptoms in late adolescence: the
      TRAILS study.
AB  - OBJECTIVE: Functional somatic symptoms (FSSs) are physical symptoms that cannot
      be (fully) explained by organic pathology. FSSs are very common among children
      and adolescents, yet their etiology is largely unknown. We hypothesize that (a)
      the experience of family disruption due to parental divorce or parental death
      increases FSSs in adolescents; (b) symptoms of depression and anxiety contribute
      to the relationship between family disruption and FSSs; (c) girls are more
      vulnerable to these effects than boys. METHOD: Data were obtained from the
      prospective population cohort of Dutch adolescents of the Tracking Adolescents'
      Individual Lives Survey (N = 2,230), aged 10 to 12 years at baseline. FSSs were
      assessed using the Somatic Complaints subscale of the Youth Self-Report. Parental
      divorce and parental death were assessed with self-reports. Both outcome and
      predictors were assessed during 3 assessment waves over the course of 5 years.
      Linear mixed models were used to investigate associations between both types of
      family disruption and FSSs. RESULTS: An interaction with age was found for
      parental divorce (B = 0.01, p = .02) and parental death (B = 0.03, p = .04),
      indicating that the influence of family disruption on FSSs increases during
      adolescence. This relationship seems to be partly explained by symptoms of
      depression and anxiety. No gender differences were found with regard to the
      effects of family disruption on FSSs. CONCLUSIONS: Family disruption is
      associated with an increased level of FSSs in late adolescence in both genders.
      This relationship is partly explained by symptoms of depression and/or anxiety.

PMID- 24588634
TI  - The effect of photodynamic action on leakage of ions through liposomal membranes
      that contain oxidatively modified lipids.
AB  - Singlet oxygen, created in photosensitization, peroxidizes unsaturated fatty
      acids of the membrane's lipids. This generates alcoholic or aldehyde groups at
      double bonds' breakage points. In a previous study, we examined the leakage of a
      K(+) -induced cross-membrane electric potential of liposomes that undergo
      photosensitization. The question remains to what extent peroxidized lipids can
      compromise the stability of the membrane. In this study, we studied the effect of
      the oxidatively modified lipids PGPC and ALDOPC in the membrane on its stability,
      by monitoring the membrane electric potential with the potentiometric dye
      DiSC(2)(5). As the content of the modified lipids increases the membrane becomes
      less stable, and even at just 2% of the modified lipids the membrane's integrity
      is affected, in respect to the leakage of ions through it. When the liposomes
      that contain the modified lipids undergo photosensitization by hematoporphyrin,
      the lipid bilayer becomes even more unstable and passage of ions is accelerated.
      We conclude that the existence of lipids with a shortened fatty acid that is
      terminated by a carboxylic acid or an aldehyde and more so when photosensitized
      damage occurs to unsaturated fatty acids in lecithin, add up to a critical
      alteration of the membrane, which becomes leaky to ions.

PMID- 24588635
TI  - Water relations of Robinia pseudoacacia L.: do vessels cavitate and refill
      diurnally or are R-shaped curves invalid in Robinia?
AB  - Since 2005, an unresolved debate has questioned whether R-shaped vulnerability
      curves (VCs) might be an artefact of the centrifuge method of measuring VCs. VCs
      with R-shape show loss of stem conductivity from approximately zero tension, and
      if true, this suggests that some plants either refill embolized vessels every
      night or function well with a high percentage of vessels permanently embolized.
      The R-shaped curves occur more in species with vessels greater than half the
      length of the segments spun in a centrifuge. Many have hypothesized that the
      embolism is seeded by agents (bubbles or particles) entering the stem end and
      travelling towards the axis of rotation in long vessels, causing premature
      cavitation. VCs were measured on Robinia pseudoacacia L. by three different
      techniques to yield three different VCs; R-shaped: Cavitron P50  = 0.30 MPa and S
      shaped: air injection P50  = 1.48 MPa and bench top dehydration P50  = 3.57 MPa.
      Stem conductivity measured in the Cavitron was unstable and is a function of
      vessel length when measured repeatedly with constant tension, and this
      observation is discussed in terms of stability of air bubbles drawn into cut-open
      vessels during repeated Cavitron measurement of conductivity; hence, R-shaped
      curves measured in a Cavitron are probably invalid.

PMID- 24588636
TI  - Reply to Dr. Gordon Parker's critique of DSM-5 mood disorders.

PMID- 24588637
TI  - Dectin-2 promotes house dust mite-induced T helper type 2 and type 17 cell
      differentiation and allergic airway inflammation in mice.
AB  - The fact that sensitization against fungi is closely related to the severity of
      asthma suggests that immune systems recognizing fungi are involved in the
      pathogenesis of severe asthma. Recently, Dectin-2 (gene symbol, Clec4n), a C-type
      lectin receptor, has been shown to function as not only a major pattern
      recognition receptor for fungi, but also a receptor for some components of house
      dust mite (HDM) extract, a major allergen for asthma. However, the roles of
      Dectin-2 in the induction of HDM-induced allergic airway inflammation remain
      largely unknown. Our objective was to determine the roles of Dectin-2 in HDM
      induced allergic airway inflammation. We examined the roles of Dectin-2 in the
      induction of HDM-induced T helper (Th) 2 and Th17 cell differentiation and
      subsequent allergic airway inflammation by using Clec4n-deficient (Clec4n(-/-))
      mice. We also investigated Dectin-2-expressing cells in the lung and their roles
      in HDM-induced allergic airway inflammation. Clec4n(-/-) mice showed
      significantly attenuated HDM-induced allergic airway inflammation and decreased
      Th2 and Th17 cell differentiation. Dectin-2 mRNA, together with Dectin-3 and Fc
      receptor-gamma mRNAs, was expressed in CD11b(+) dendritic cells (DCs), but not in
      CD4(+) T cells or epithelial cells in the lung. CD11b(+) DCs isolated from
      Clec4n(-/-) mice expressed lower amounts of proinflammatory cytokines and
      costimulatory molecules, which could lead to Th2 and Th17 cell differentiation
      than those from wild-type mice. HDM-pulsed Clec4n(-/-) DCs were less efficient
      for the induction of allergic airway inflammation than HDM-pulsed wild-type DCs.
      In conclusion, Dectin-2 expressed on CD11b(+) DCs promotes HDM-induced Th2 and
      Th17 cell differentiation and allergic airway inflammation. 

PMID- 24588638
TI  - Response to comment on "Toxicity and mutagenicity of Gulf of Mexico waters during
      and after the deepwater horizon oil spill".

PMID- 24588639
TI  - Age, gender, kinship and caregiver burden in amyotrophic lateral sclerosis.
AB  - Amyotrophic lateral sclerosis is a neurodegenerative disease that affects the
      motor neurons and causes progressive physical impairment. Also, other functions,
      such as breathing, swallowing and speech are compromised, and the loss of
      independence makes caregiver burden extremely high. The present study aimed at
      evaluating the differences in the caregiver burden due to age, gender and
      kinship. Women reported a higher physical and social burden than men, and
      partners scored higher in several dimensions of the caregiver burden when
      compared to sons and daughters. With respect to adult child caregivers, daughters
      reported higher levels of developmental burden than sons. Age has a significant
      impact on the caregiver burden, especially for the time dedicated to assistance
      and physical burden; disease severity is significantly related to the physical
      burden as well, and also with the developmental burden.

PMID- 24588640
TI  - Air-breathing fishes.

PMID- 24588641
TI  - Metabolic and embryonic responses to terrestrial incubation of Fundulus grandis
      embryos across a temperature gradient.
AB  - This study simulated terrestrial incubation and measured rates of embryogenesis,
      nitrogen elimination, heart rate, lactate production, maximum length of time a
      hatch could be delayed and developmental responses of terrestrially incubated
      Gulf killifish Fundulus grandis embryos at temperatures ranging from 20 to 30
      degrees  C. Temperature had a positive relationship with rate of embryogenesis,
      but a negative relationship with extent of extended incubation. The 30 degrees  C
      treatment reached embryonic maturity 6 days before the 20 degrees  C treatment.
      Embryos hatched between intervals of 240 and 336, 144 and 288, 96 and 240 and 96
      and 192 h after reaching developmental maturity for the 20, 23, 26 and 30 degrees
      C treatments. Significantly higher concentrations of total nitrogen, in the form
      of ammonia and urea, were recorded in the 20 and 30 degrees  C treatments. While
      temperature significantly influenced lactate and ATP concentrations, no
      significant influence of time of incubation was detected. Terrestrial embryos
      displayed an ability to develop quickly during embryogenesis and prolong
      incubation for an extended period of time after reaching embryonic maturity. This
      adaptation may be a life-history trait used to minimize asynchronous hatching,
      cannibalism and cohort size heterogeneity. 

PMID- 24588642
TI  - Roles of air stored in burrows of the mudskipper Boleophthalmus pectinirostris
      for adult respiration and embryonic development.
AB  - Air was stored in 90% of Boleophthalmus pectinirostris burrows in summer breeding
      months when fish were active on the mudflat surface during low tide but only in
      50% of burrows in overwintering months when the fish confined themselves to
      burrows. The volume of gas recovered from the burrows ranged from 30 to > 400 ml.
      The partial pressure of oxygen (PO2) of the gas varied from 5 to 20 kPa and was
      inversely related to the partial pressure of carbon dioxide (PCO2) in all but the
      wintering periods. Sampling in July demonstrated that gas was stored in both male
      and female burrows with no difference in volume, PO2 or PCO2 between them. Adult
      fish were able to survive total submersion in hypoxic (PO2 = 1.96 kPa) water for
      8 h, but no embryos survived to hatch in the hypoxic aquatic environment. Thus,
      the deposited air appears to be a crucial source of oxygen for the embryos
      developing in the egg chamber of the burrow, but may play only a subsidiary role
      for adult respiration during presumed high-tide confinement.

PMID- 24588643
TI  - The effect of sustained hypoxia on the cardio-respiratory response of bowfin Amia
      calva: implications for changes in the oxygen transport system.
AB  - This study examined mechanisms underlying cardio-respiratory acclimation to
      moderate sustained hypoxia (6.0 kPa for 7 days at 22 degrees  C) in the bowfin
      Amia calva, a facultative air-breathing fish. This level of hypoxia is slightly
      below the critical oxygen tension (pcrit ) of A. calva denied access to air (mean
      +/- s.e. = 9.3 +/- 1.0 kPa). Before exposure to sustained hypoxia, A. calva with
      access to air increased air-breathing frequency on exposure to acute progressive
      hypoxia while A. calva without access to air increased gill-breathing frequency.
      Exposure to sustained hypoxia increased the gill ventilation response to acute
      progressive hypoxia in A. calva without access to air, regardless of whether they
      had access to air or not during the sustained hypoxia. Additionally, there was a
      decrease in Hb-O2 binding affinity in these fish. This suggests that, in A.
      calva, acclimation to hypoxia elicits changes that increase oxygen delivery to
      the gas exchange surface for oxygen uptake and reduce haemoglobin affinity to
      enhance oxygen delivery to the tissues.

PMID- 24588644
TI  - Interactions of phosphatase and tensin homologue (PTEN) proteins with
      phosphatidylinositol phosphates: insights from molecular dynamics simulations of
      PTEN and voltage sensitive phosphatase.
AB  - The phosphatase and tensin homologue (PTEN) and the Ciona intestinalis voltage
      sensitive phosphatase (Ci-VSP) are both phosphatidylinositol phosphate (PIP)
      phosphatases that contain a C2 domain. PTEN is a tumor suppressor protein that
      acts as a phosphatase on PIP3 in mammalian cell membranes. It contains two
      principal domains: a phosphatase domain (PD) and a C2 domain. Despite detailed
      structural and functional characterization, less is known about its mechanism of
      interaction with PIP-containing lipid bilayers. Ci-VSP consists of an N-terminal
      transmembrane voltage sensor domain and a C-terminal PTEN domain, which in turn
      contains a PD and a C2 domain. The nature of the interaction of the PTEN domain
      of Ci-VSP with membranes has not been well established. We have used multiscale
      molecular dynamics simulations to define the interaction mechanisms of PTEN and
      of the Ci-VSP PTEN domains with PIP-containing lipid bilayers. Our results
      suggest a novel mechanism of association of the PTEN with such bilayers, in which
      an initial electrostatics-driven encounter of the protein and bilayer is followed
      by reorientation of the protein to optimize its interactions with PIP molecules
      in the membrane. Although a PIP3 molecule binds close to the active site of PTEN,
      our simulations suggest a further conformational change of the protein may be
      required for catalytically productive binding to occur. Ci-VSP interacted with
      membranes in an orientation comparable to that of PTEN but bound directly to PIP
      containing membranes without a subsequent reorientation step. Again, PIP3 bound
      close to the active site of the Ci-VSP PD, but not in a catalytically productive
      manner. Interactions of Ci-VSP with the bilayer induced clustering of PIP
      molecules around the protein. 

PMID- 24588645
TI  - Renal hemosiderosis and rapidly progressive glomerulonephritis associated with
      primary hemochromatosis.
AB  - Hereditary hemochromatosis leads to the accumulation of iron in many organs
      including the liver, spleen and heart and results in injury and dysfunction of
      these organs. On the other hand, iron accumulation and functional impairment in
      kidney is extremely rare. We report a 61-year-old male patient with hereditary
      hemochromatosis, in whom the renal function was deteriorated rapidly. Renal
      biopsy revealed crescentic glomeruli and hemosiderin accumulation in tubular
      epithelial cells.

PMID- 24588646
TI  - What are the latest pharmacotherapy options for small bowel adenocarcinoma?
AB  - Incidence of small bowel adenocarcinoma is slowly but steadily increasing. As we
      gain more knowledge of the molecular basis of this disease, we may be able to
      approach it via using novel biologic or targeted therapies with or without
      traditional chemotherapy agents. In the meantime, early diagnosis is still best
      as it prompts early surgical resection and offers potential cure. The role of
      adjuvant and neoadjuvant therapy is currently being explored in clinical trials.
      Several clinical trials have suggested that first-line chemotherapy for patients
      with metastatic disease should consist of either 5-fluorouracil-leucovorin
      oxalipatin or capecitabine-oxaliplatin, while 5-fluorouracil-leucovorin
      irinotecan can be reserved for second-line treatment. However, we realize the
      limitations of these studies, given their small sample size and/or retrospective
      nature. Single-agent 5-fluorouracil/capecitabine should be considered in patients
      who are either intolerant to or experience significant side effects with
      oxaliplatin or irinotecan. We believe that cancers originating in the ampulla of
      Vater probably deserve a prospective randomized trial of cisplatin-gemcitabine,
      the current standard of therapy for advanced biliary malignancies.

PMID- 24588647
TI  - Investigating cataract referral practices used by Australian optometrists.
AB  - BACKGROUND: The patient pathway to cataract surgery in Australia generally begins
      with optometric services; however, little is known about the cataract surgery
      referral criteria used by optometrists in Australia. METHODS: Members of
      Optometrists Association Australia were invited to complete an online survey in
      April 2013. The survey elicited information on practice demographics,
      professional characteristics of optometrists and cataract surgery referral
      considerations. RESULTS: We received responses from 533 of 4272 (13 per cent)
      practising optometrists. Over three-quarters (407 of 528, 77 per cent) indicated
      a visual acuity (VA) cataract referral benchmark of 6/9 to 6/12. Almost all
      respondents (499 out of 532, 94 per cent) stated they included glare sensitivity
      as part of their referral criteria, whereas a considerably lower proportion (40
      of 528, eight per cent) used contrast sensitivity testing. Patient-centred
      factors such as hobbies (94 per cent) and driving (73 per cent) featured in the
      decision to refer patients sooner, while a patient not wanting surgery (79 per
      cent) was the most frequent reason cited for delaying referral. Respondents
      practising in more advantaged socioeconomic areas were 2.4 times more likely to
      refer privately (95% CI 1.6-3.6) and less likely to consider surgical costs as an
      important consideration (p < 0.001). Almost all respondents (97 per cent) who
      referred publicly discussed public hospital waiting times with their patients
      (median minimum wait estimate of 12 to 18 months), compared to the smaller
      proportion (64 per cent) of respondents discussing private waiting times (median
      minimum wait estimate of one to two months). CONCLUSION: While modest reductions
      in VA were sufficient to prompt referral for cataract surgery by Australian
      optometrists, patient-reported visual disability guided the optometrist's overall
      referral decision. Socioeconomic status of practice location influenced the
      choice to refer publicly versus privately and surgical costs were also
      considered.

PMID- 24588648
TI  - Effects of video-feedback on the communication, clinical competence and
      motivational interviewing skills of practice nurses: a pre-test posttest control
      group study.
AB  - AIMS: To examine the effects of individual video-feedback on the generic
      communication skills, clinical competence (i.e. adherence to practice guidelines)
      and motivational interviewing skills of experienced practice nurses working in
      primary care. BACKGROUND: Continuing professional education may be necessary to
      refresh and reflect on the communication and motivational interviewing skills of
      experienced primary care practice nurses. A video-feedback method was designed to
      improve these skills. DESIGN: Pre-test/posttest control group design. METHODS:
      Seventeen Dutch practice nurses and 325 patients participated between June 2010
      June 2011. Nurse-patient consultations were videotaped at two moments (T0 and
      T1), with an interval of 3-6 months. The videotaped consultations were rated
      using two protocols: the Maastrichtse Anamnese en Advies Scorelijst met globale
      items (MAAS-global) and the Behaviour Change Counselling Index. Before the
      recordings, nurses were allocated to a control or video-feedback group. Nurses
      allocated to the video-feedback group received video-feedback between T0 and T1.
      Data were analysed using multilevel linear or logistic regression. RESULTS:
      Nurses who received video-feedback appeared to pay significantly more attention
      to patients' request for help, their physical examination and gave significantly
      more understandable information. With respect to motivational interviewing,
      nurses who received video-feedback appeared to pay more attention to 'agenda
      setting and permission seeking' during their consultations. CONCLUSION: Video
      feedback is a potentially effective method to improve practice nurses' generic
      communication skills. Although a single video-feedback session does not seem
      sufficient to increase all motivational interviewing skills, significant
      improvement in some specific skills was found. Nurses' clinical competences were
      not altered after feedback due to already high standards.

PMID- 24588649
TI  - Uses and misuses of treatments for ADHD. The second Birgit Olsson lecture.
AB  - BACKGROUND: Medication in attention deficit/hyperactivity disorder (ADHD) is so
      controversial that in some countries many children go untreated, while in others
      the prevalence of medication has become very high, and possibly even higher than
      the rate of ADHD. AIMS: This lecture addresses the reasons for overuse and the
      obstacles to adequate use. METHODS: Clinical and scientific literature is
      reviewed, with emphasis on published meta-analyses and national guidelines.
      RESULTS AND CONCLUSIONS: The lecture suggests that overuse is associated with
      economic forces affecting prescribers, while underuse may come about in some
      European countries because we have overestimated the hazards of drugs,
      overestimated the value of non-pharmaceutical interventions or underestimated the
      severity of disorder.

PMID- 24588650
TI  - Enzyme architecture: remarkably similar transition states for triosephosphate
      isomerase-catalyzed reactions of the whole substrate and the substrate in pieces.
AB  - Values of (k(cat)/K(m))GAP for triosephosphate isomerase-catalyzed reactions of
      (R)-glyceraldehyde 3-phosphate and k(cat)/K(HPi)K(GA) for reactions of the
      substrate pieces glycolaldehyde and HPO3(2-) have been determined for wild-type
      and the following TIM mutants: I172V, I172A, L232A, and P168A (TIM from
      Trypanosoma brucei brucei); a 208-TGAG for 208-YGGS loop 7 replacement mutant
      (L7RM, TIM from chicken muscle); and, Y208T, Y208S, Y208A, Y208F and S211A (yeast
      TIM). A superb linear logarithmic correlation, with slope of 1.04 +/- 0.03, is
      observed between the kinetic parameters for wild-type and most mutant enzymes,
      with positive deviations for L232A and L7RM. The unit slope shows that most
      mutations result in an identical change in the activation barriers for the
      catalyzed reactions of whole substrate and substrate pieces, so that the two
      transition states are stabilized by similar interactions with the protein
      catalyst. This is consistent with a role for dianions as active spectators, which
      hold TIM in a catalytically active caged form.

PMID- 24588651
TI  - Oxygen-sulfur exchange and the gas-phase reactivity of cobalt sulfide cluster
      anions with molecular oxygen.
AB  - We present here a study of gas-phase reactivity of cobalt sulfide cluster anions
      Co(m)S(n)(-) with molecular oxygen. Nascent Co(m)S(n)(-) clusters were prepared
      via a laser ablation source and reacted with oxygen in a fast flow reactor under
      thermal collision conditions. We chose (18)O2 in place of (16)O2 to avoid mass
      degeneration with sulfur, and a time-of-flight (TOF) mass spectrometer was used
      to detect the cluster distributions in the absence and presence of the reactant.
      It was found that oxygen-sulfur exchange occurs in the reactions for those with
      specific compositions (CoS)(n)(-) and (CoS)(n)S(-) (n = 2-5) according to a
      consistent pathway, "Co(m)S(n)(-) + (18)O2 -> Co(m)S(n-1)(18)O(-) + S(18)O".
      Typically, for "Co2S2(-) + (18)O2" we have calculated the reaction coordinates by
      employing the density functional theory (DFT), where both the oxygen-sulfur
      exchange and SO molecule release are thermodynamically and kinetically favorable.
      It is noteworthy that the reaction with molecular oxygen (triplet ground state)
      needs to overcome a spin excitation as well as a large O-O activation energy.
      This study sheds light on the activation of molecular oxygen by cobalt sulfides
      on one hand and also provides insight into the regeneration mechanism of cobalt
      oxides from the counterpart sulfides in the presence of oxygen gas on the other
      hand.

PMID- 24588653
TI  - Surgical site infections in standard neurosurgery procedures- a study of
      incidence, impact and potential risk factors.
AB  - OBJECTIVES. Surgical site infections (SSIs) may be devastating for the patient
      and they carry high economic costs. Studies of SSI after neurosurgery report an
      incidence of 1-11%. However, patient material, follow-up time and definition of
      SSI have varied. In the present study we prospectively recorded the prevalence of
      SSI 3 months after standard intracranial neurosurgical procedures. The incidence,
      impact and risk factors of SSI were analysed. METHODS. We included patients
      admitted during 2010 to our unit for postoperative care after standard
      neurosurgical procedures. SSI was defined as evident with positive cultures from
      surgical samples or CSF, and/or purulent discharge during reoperation. Follow-up
      was done after 3 and 12 months and statistics was obtained after 3 months. The
      predictive values on the outcome of demographic and clinical factors describing
      the surgical procedure were evaluated using linear regression. RESULTS. A total
      of 448 patients were included in the study and underwent a total of 466
      procedures. Within 3 and 12 months, 33 and 88 patients, respectively, had died.
      Of the surviving patients, 20 (4.3% of procedures) developed infections within 3
      months and another 3 (4.9% of procedures) within 12 months. Risk factors for SSI
      were meningioma, longer operation time, craniotomy, dural substitute, and staples
      in wound closure. Patients with SSI had significantly longer hospital stay.
      Multivariate analysis showed that factors found significant in univariate
      analysis frequently occur together. DISCUSSION. We studied the prevalence of SSI
      after 3 and 12 months in a prospective 1-year material with standard
      neurosurgical procedures and found it to be 4.3% and 4.9%, respectively. The
      analysis of the results showed that a combination of parameters indicating a
      longer and more complicated procedure predicted the development of SSI. Our
      conclusion is that the prevention of SSI has to be done at many levels,
      especially with patients undergoing long surgical procedures.

PMID- 24588654
TI  - Z-Ligustilide inhibits benzo(a)pyrene-induced CYP1A1 upregulation in cultured
      human keratinocytes via ROS-dependent Nrf2 activation.
AB  - Benzo(a)pyrene (BaP), a polycyclic aromatic hydrocarbon (PAH), is an
      environmental contaminant that can induce cytochrome P4501A1 (CYP1A1)
      upregulation via aryl hydrocarbon receptor (AhR) activation and provoke
      inflammation. Here, we investigated the effect of Z-Ligustilide, an active
      ingredient isolated from the medicinal plants Cnidium officinale and Angelica
      acutiloba, on BaP-induced CYP1A1 upregulation in normal human epidermal
      keratinocytes (NHEKs) as well as its underlying mechanisms. Z-Ligustilide
      significantly inhibited BaP-induced CYP1A1 upregulation in NHEKs. Treatment of
      NHEKs with Z-Ligustilide induced Nuclear factor-E2-related factor 2 (Nrf2)
      nuclear translocation and expression of the Nrf2-regulated genes for haeme
      oxygenase-1 (HO-1) and NAD(P)H: quinine oxidoreductase-1 (NQO1). AhR silencing,
      SB203580 (a p38 inhibitor), SP600125 (a JNK inhibitor), U0126 (a MEK inhibitor)
      and LY294002 (a PI3K inhibitor) did not suppress Z-Ligustilide-induced Nrf2
      activation. Moreover, treatment of NHEKs with Z-Ligustilide increased reactive
      oxygen species (ROS) and L-N-acetylcysteine (L-NAC, an antioxidant) attenuated Z
      ligustilide-induced Nrf2 nuclear translocation and HO-1 expression. L-NAC or
      knock-down of Nrf2 significantly attenuated the inhibitory effects of Z
      Ligustilide on BaP-induced CYP1A1 upregulation in NHEKs. Taken together, these
      findings suggest that Z-Ligustilide can suppress BaP-induced CYP1A1 upregulation
      through ROS-dependent Nrf2 pathway activation and may be beneficial in preventing
      or treating BaP-induced skin damage.

PMID- 24588655
TI  - C1-symmetrical titanium(IV) complexes of salan ligands with differently
      substituted aromatic rings: enhanced cytotoxic activity.
AB  - Diaminobis(phenolato) ("salan") titanium(IV) complexes of differently substituted
      aromatic rings were synthesized, and their hydrolytic stability and cytotoxicity
      were analyzed and compared to those of the C2-symmertrical analogues and their
      equimolar mixtures. The hydrolytic stability of the asymmetrical complexes was in
      between those of the symmetrical analogues, implying an additive influence of the
      ligand structural parameters. Most mixed halogenated/nitrated complexes showed a
      marked improvement of cytotoxic activity relative to the symmetrical analogues
      and their mixtures, with IC50 values as low as <1 MUM corresponding to activity
      exceeding that of cisplatin by up to 30-fold. In contrast, asymmetrical complexes
      with substitutions of similar properties revealed an added influence of both,
      with cytotoxicity in between those of the symmetrical analogues. With the
      presumption that the active species is generally a polynuclear hydrolysis product
      kept in mind, it is overall evident that particular ligand design and fine-tuning
      of the parameters of influence including hydrophilicity and hydrophobicity are
      essential for maximizing biological efficiency. 

PMID- 24588656
TI  - Emotional distress and compassionate responses in palliative care decision-making
      consultations.
AB  - BACKGROUND: Seriously ill hospitalized patients and their loved ones are
      frequently faced with complex treatment decisions laden with expressions of
      emotional distress during palliative care (PC) consultations. Little is known
      about these emotional expressions or the compassionate responses providers make
      and how common these are in PC decision-making conversations. OBJECTIVES: To
      describe the types and frequency of emotional distress that patients and loved
      ones express and how providers respond to these emotions during PC decision
      making consultations with seriously ill hospitalized patients. METHODS: We used a
      quantitative descriptive approach to analyze 71 audio-recorded inpatient PC
      decision-making consultations for emotional distress and clinicians' responses to
      those emotions using reliable and established methods. RESULTS: A total of 69% of
      conversations contained at least one expression of emotional distress. The per
      conversation frequency of expressions of emotional distress ranged from 1 to 10.
      Anxiety/fear were the most frequently encountered emotions (48.4%) followed by
      sadness (35.5%) and anger/frustration (16.1%). More than half of the emotions
      related to the patient's feelings (53.6%) and 41.9% were related to the loved
      ones' own emotions. The majority of emotions were moderate in intensity (65.8%)
      followed by strong (20.7%) and mild (13.5%). Clinicians responded to a majority
      of emotions with a compassionate response (75.7%) followed by those with medical
      content (21.9%) and very few were ignored (1.3%). CONCLUSIONS: Expressions of
      emotional distress are common during PC consultations and are usually met with
      compassionate responses by the clinician.

PMID- 24588657
TI  - An automated turbidimetric method for fibrinogen determination in dogs.
AB  - BACKGROUND: Several methods have been used for fibrinogen determination in dogs,
      but to the authors' knowledge, methods based on ammonium sulfate precipitation
      have not yet been reported in this species. OBJECTIVES: The aim of this study was
      to develop and validate an automated method based on ammonium sulfate
      precipitation for canine fibrinogen determination. METHODS: A reagent containing
      ammonium sulfate, sodium chloride, and K2 EDTA was used to precipitate fibrinogen
      at a final ammonium sulfate concentration of 0.57 M and final turbidity was
      measured on a Cobas Mira Plus autoanalyzer. Analytic validation included
      imprecision, accuracy, comparison with reference method (Clauss), limits of
      detection and quantification, and the evaluation of the influence of different
      anticoagulants. For diagnostic validation, fibrinogen was determined in a group
      of Beagle dogs before and after neutering, and in dogs affected by diseases known
      to produce low fibrinogen plasma concentration, such as liver insufficiency,
      disseminated intravascular coagulation, and protein-losing enteropathy. RESULTS:
      Low imprecison (<4%), excellent recovery (>90%), and low bias (0.092 g/L) with
      respect to Clauss method indicated a high reproducibility and accuracy. Limits of
      detection and quantification were 0.01 and 0.22 g/L, respectively. The method was
      applicable in plasma samples anticoagulated with EDTA, heparin, or sodium
      citrate. The fibrinogen concentration in Beagle dogs after neutering was
      increased, and decreased in animals with disseminated intravascular coagulation,
      liver insufficiency, or gastrointestinal protein loss. CONCLUSIONS: The automated
      method validated in this study represents a rapid, cheap, and easy protocol to
      quantify canine fibrinogen in routine practice.

PMID- 24588658
TI  - Silylethynyl substituents as porphyrin protecting groups for solubilization and
      selectivity control.
AB  - Silylethynyl substituents are proposed as protecting groups for porphyrin
      derivatives to enhance their solubility and enable regioselective
      functionalization. After usage as protecting groups, silylethynyl groups at the
      meso-positions can be efficiently removed upon heating with aqueous H2SO4 in the
      presence of a surfactant. This approach was applied to the preparation of
      unsymmetrically beta-substituted porphyrins and porphin-porphyrin oligomers,
      which were inaccessible by conventional methods. 

PMID- 24588652
TI  - Update on leukotriene, lipoxin and oxoeicosanoid receptors: IUPHAR Review 7.
AB  - The endogenous ligands for the LT, lipoxin (LX) and oxoeicosanoid receptors are
      bioactive products produced by the action of the lipoxygenase family of enzymes.
      The LT receptors BLT1 and BLT2 , are activated by LTB4 and the CysLT1 and CysLT2
      receptors are activated by the cysteinyl-LTs, whereas oxoeicosanoids exert their
      action through the OXE receptor. In contrast to these pro-inflammatory mediators,
      LXA4 transduces responses associated with the resolution of inflammation through
      the receptor FPR2/ALX (ALX/FPR2). The aim of the present review is to give a
      state of the field on these receptors, with focus on recent important findings.
      For example, BLT1 receptor signalling in cancer and the dual role of the BLT2
      receptor in pro- and anti-inflammatory actions have added more complexity to
      lipid mediator signalling. Furthermore, a cross-talk between the CysLT and P2Y
      receptor systems has been described, and also the presence of novel receptors for
      cysteinyl-LTs, such as GPR17 and GPR99. Finally, lipoxygenase metabolites derived
      from omega-3 essential polyunsaturated acids, the resolvins, activate the
      receptors GPR32 and ChemR23. In conclusion, the receptors for the lipoxygenase
      products make up a sophisticated and tightly controlled system of endogenous pro-
      and anti-inflammatory signalling in physiology and pathology. 

PMID- 24588659
TI  - Screening methods to identify indole derivatives that protect against reactive
      oxygen species induced tryptophan oxidation in proteins.
AB  - Oxidative damage to proteins is one of the most prominent chemical degradation
      pathways that are of concern for drug product development in the biotechnology
      industry. Especially susceptible to oxidation are the Met and Trp residues in
      proteins. While L-Met and L-Trp have been shown to act as antioxidants typically
      protecting proteins against Met and Trp oxidation, respectively, l-Trp has been
      shown to be particularly sensitive to light, thereby producing various reactive
      oxygen species (ROS), including H2O2. There is hence a need to identify
      nonphotosensitive molecules that can protect Trp oxidation in proteins so that
      they can be easily handled under drug product manufacturing conditions. A
      combination of screening methods, namely, cyclic voltammetry (CV) and hydrogen
      peroxide generation upon photoirradiation, was used to screen several molecules
      to identify compounds that can act as antioxidants. Specifically, indole and
      tryptophan with hydroxy groups on the six-membered aromatic ring were found to
      have lower oxidation potentials than the parent compounds and produced the least
      amount of H2O2 upon light exposure. These derivatives were also found to
      sufficiently protect tryptophan oxidation in mAb1 against a variety of reactive
      oxygen species such as alkyl peroxides, hydroxyl radicals, and singlet oxygen and
      may be useful as part of the formulation toolkit to protect against protein
      degradation via oxidation.

PMID- 24588660
TI  - Nanoparticle organization through photoinduced bulk mass transfer.
AB  - A series of dipolar triphenylaminoazo derivatives, with largely distinct charge
      transfer and glass transition temperatures, has been synthesized. Their
      photomigration capability in the solid state to form surface relief gratings
      (SRGs) under interferential illumination has been investigated with respect to
      their photochromic properties and showed a prevailing influence of the bulkiness
      of the azo substituent. The azo mass transfer was utilized to efficiently
      photoalign 200 nm polystyrene nanoparticles along the SRG crests, which were
      initially deposited on nonirradiated azo surfaces. In contrast, nanoparticles
      spin cast on prestructured surface relief gratings were localized in the troughs
      of the periodic structures. These distinct locations point out the ability of
      isotropic and amorphous photochromic thin films to collectively move and organize
      nano-objects in an ordered fashion through the use of polarized illumination.
      This versatile approach opens the path to optically aligned ensembles of
      individual nano-objects over large areas, which can be further combined with
      metallic conductive or magnetic coating to create novel functional
      nanostructures. 

PMID- 24588661
TI  - A novel benzenediamine derivate rescued mice from experimental sepsis by
      attenuating proinflammatory mediators via IRAK4.
AB  - We designed and synthesized a novel benzenediamine derivate, FC-99, that was
      tested for its ability to protect mice from experimental sepsis. Moreover, we
      sought to determine whether FC-99 could control a bacterial infection and to
      clarify the mechanism by which FC-99 inhibited LPS-activated macrophages. The
      effects of FC-99 on inflammation were evaluated in two experimental sepsis models
      and in cultured macrophages. Microarrays and docking and molecular dynamics
      simulations were used to determine the target of FC-99. Surface plasmon resonance
      and molecular detection were performed to confirm the direct interaction of FC-99
      with its target. FC-99 protected mice from experimental sepsis. The mice that
      received FC-99 exhibited a diminished inflammatory response, had a lower local
      bacterial burden, and experienced a significantly improved survival rate. Genome
      wide transcriptional profiling of FC-99-treated macrophages identified IRAK4 as a
      drug-regulated gene involved in LPS/TLR4 signaling. A computer search and
      calculations indicated that IRAK4 directly interacted with FC-99. Surface plasmon
      resonance, IRAK4-regulated signaling pathway analysis, and gene expression
      profiling of proinflammatory mediators confirmed the direct interaction between
      FC-99 and IRAK4. FC-99 is a potential therapeutic molecule for sepsis that
      alleviated experimental sepsis by directly inhibiting IRAK4 activation, which
      represents a novel target for sepsis therapy. 

PMID- 24588662
TI  - A comparison of progestogens or oral contraceptives and gonadotropin-releasing
      hormone agonists for the treatment of endometriosis: a systematic review.
AB  - OBJECTIVE: This systematic review examined the use of progestogens or oral
      contraceptives and gonadotropin-releasing hormone (GnRH) agonists for the
      treatment of endometriosis. RESEARCH DESIGN AND METHODS: Inclusion criteria were:
      i) randomized controlled trials (RCTs); ii) comparison of progestogens with GnRH
      agonists for treatment of endometriosis; and iii) endometriosis diagnosed by
      laparoscopy or laparotomy. MAIN OUTCOME MEASURES: Pelvic pain, bone mineral
      density, serum estradiol level, and side effects. RESULTS: Of 128 articles
      identified, there were four RCTs comparing the use of progestogens and GnRH
      agonists. In three studies a progestogen (gestrinone, lynestrenol, or dienogest)
      was compared with leuprolide. In one study, ethinyl estradiol/norethindrone was
      compared with leuprolide/norethindrone. A meta-analysis was not possible as the
      studies varied markedly in their protocols, inclusion criteria, and the drugs and
      doses administered. Leuprolide was as effective as gestrinone, dienogest, and
      continuous oral contraceptives (OCs) for the relief of endometriosis-related
      pain, whereas it was superior to lynestrenol. Leuprolide was associated with a
      significant reduction in bone mineral density and estradiol levels and a higher
      incidence of hot flushes, headaches, mood changes, and vaginal dryness, whereas
      progestogens were associated with higher incidences of weight gain and acne.
      CONCLUSIONS: These results suggest that progestogens or OCs may be used as first
      line therapy for endometriosis.

PMID- 24588663
TI  - Dynamics of MutS-mismatched DNA complexes are predictive of their repair
      phenotypes.
AB  - MutS recognizes base-base mismatches and base insertions/deletions (IDLs) in
      newly replicated DNA. Specific interactions between MutS and these errors trigger
      a cascade of protein-protein interactions that ultimately lead to their repair.
      The inability to explain why different DNA errors are repaired with widely
      varying efficiencies in vivo remains an outstanding example of our limited
      knowledge of this process. Here, we present single-molecule Forster resonance
      energy transfer measurements of the DNA bending dynamics induced by Thermus
      aquaticus MutS and the E41A mutant of MutS, which is known to have error specific
      deficiencies in signaling repair. We compared three DNA mismatches/IDLs (T-bulge,
      GT, and CC) with repair efficiencies ranging from high to low. We identify three
      dominant DNA bending states [slightly bent/unbent (U), intermediately bent (I),
      and significantly bent (B)] and find that the kinetics of interconverting among
      states varies widely for different complexes. The increased stability of MutS
      mismatch/IDL complexes is associated with stabilization of U and lowering of the
      B to U transition barrier. Destabilization of U is always accompanied by a
      destabilization of B, supporting the suggestion that B is a "required" precursor
      to U. Comparison of MutS and MutS-E41A dynamics on GT and the T-bulge suggests
      that hydrogen bonding to MutS facilitates the changes in base-base hydrogen
      bonding that are required to achieve the U state, which has been implicated in
      repair signaling. Taken together with repair propensities, our data suggest that
      the bending kinetics of MutS-mismatched DNA complexes may control the entry into
      functional pathways for downstream signaling of repair. 

PMID- 24588664
TI  - Differentiation of benign from malignant thyroid nodules with acoustic radiation
      force impulse technique.
AB  - OBJECTIVE: The aim of our study was to assess the performance of acoustic
      radiation force impulse (ARFI) imaging to differentiate benign from malignant
      thyroid nodules. METHODS: 182 patients who needed thyroid surgery were examined.
      All patients and 50 healthy volunteers underwent ARFI sonoelastography, which
      quantitatively analysed the elasticity and hardness of the nodule's centre and
      periphery. RESULTS: ARFI values showed a statistical significance between
      malignant nodules and benign nodules and common thyroid parenchyma, in both the
      centre and periphery of nodules (p < 0.01). There was no significant difference
      between benign nodules and common thyroid parenchyma in either the nodule's
      centre or periphery (p > 0.05). There was no significant difference between the
      nodule's centre and periphery of the elastic parameters in both the benign and
      malignant nodules. There was a statistically significant difference among the two
      areas (the central group and the peripheral group) under the receiver operating
      characteristic curve, and the optimal model was the peripheral group. For
      differentiation of malignant from benign nodules, the sensitivity and specificity
      were 96.3% and 96.2%, respectively, when 2.545 m s(-1) was chosen as a cut-off
      value in the peripheral group. CONCLUSION: ARFI imaging may be helpful to
      differentiate benign nodules from malignant thyroid nodules. The selecting
      measurement position is important in ARFI imaging, and it has good diagnostic
      value in clinical applications. ADVANCES IN KNOWLEDGE: This study shows the
      diagnostic contribution of ARFI imaging in thyroid lesions.

PMID- 24588665
TI  - A comparative MRI study for white matter hyperintensities detection: 2D-FLAIR,
      FSE PD 2D, 3D-FLAIR and FLAIR MIP.
AB  - OBJECTIVE: The main objective of this study was to not only determine the most
      appropriate sequence for the analysis of white matter hyperintensities (WMH) on
      MRI but also to confirm the advantage of three-dimensional (3D) acquisition, as
      it has been suggested in previous studies, and to test the convenience of using
      maximum intensity projection (MIP) algorithms on 3D-fluid-attenuated inversion
      recovery (FLAIR) images for a quicker evaluation of brain MR studies. METHODS:
      The number of WMH was compared in 40 patients and a control group of 10
      volunteers using 4 different imaging modalities: two dimensional (2D)-FLAIR, 2D
      fast spin echo proton density (FSE PD), 3D-FLAIR and FLAIR MIP. Four experienced
      radiologists took part in the imaging analysis. All studies were performed on a
      1.5-T whole-body MR unit. RESULTS: A statistically significant difference between
      the number of lesions detected on 3D acquisitions (FLAIR CUBE(r) or FLAIR MIP
      sequences) compared with those on 2D-FLAIR or 2D FSE PD was demonstrated. There
      is no significant difference between 3D-FLAIR and FLAIR MIP, therefore both of
      them can be used with similar results. CONCLUSION: 3D-FLAIR sequences should
      replace conventional 2D-FLAIR and/or FSE PD sequences in the MR acquisition
      protocol when WMH are suspected. MIP reformat algorithms are less time consuming,
      therefore these can also be used to simplify the detection. ADVANCES IN
      KNOWLEDGE: 3D sequences are superior for WMH depiction. Moreover, MIP algorithms
      allow easier analyses with similar results.

PMID- 24588667
TI  - Towards transparency in cardiac radiology: should CT coronary angiography
      radiation doses be published?
AB  - This is a commentary on the use of radiation dose as a quality marker in CT
      coronary angiography. 

PMID- 24588666
TI  - Vascular anomalies: classification, imaging characteristics and implications for
      interventional radiology treatment approaches.
AB  - The term vascular anomaly represents a broad spectrum of vascular pathology,
      including proliferating vascular tumours and vascular malformations. While the
      treatment of most vascular anomalies is multifactorial, interventional radiology
      procedures, including embolic therapy, sclerotherapy and laser coagulation among
      others, are playing an increasingly important role in vascular anomaly
      management. This review discusses the diagnosis and treatment of common vascular
      malformations, with emphasis on the technique, efficacy and complications of
      different interventional radiology procedures. 

PMID- 24588668
TI  - Simultaneous integrated boost intensity-modulated radiotherapy for treatment of
      locally advanced non-small-cell lung cancer: a retrospective clinical study.
AB  - OBJECTIVE: To evaluate the clinical efficacy and safety of simultaneous
      integrated boost intensity-modulated radiotherapy (SIB-IMRT) for patients with
      locally advanced non-small-cell lung cancer (LANSCLC). METHODS: 48 patients with
      LANSCLC treated with SIB-IMRT from January 2010 to April 2012 were
      retrospectively analysed. A radiation dose of 45-63 Gy (median dose, 51.58 Gy)
      was delivered to the planning target volume (1.8-2.0 Gy daily fractions)
      simultaneously with 55.0-74.2 Gy (median dose, 63 Gy) to the planning gross
      tumour volume (2.00-2.25 Gy daily fractions). 45 patients received
      concurrent/sequential chemotherapy. The overall survival (OS), locoregional
      recurrence-free survival (LRFS) and progression-free survival (PFS) were
      estimated using the Kaplan-Meier method. Treatment-related pneumonitis and
      oesophagitis were graded according to the Common Terminology Criteria for Adverse
      Events v. 4.0. RESULTS: By 1 July 2013, 29 of the 48 patients were dead. The
      median follow-up time for the survivors was 28 months (19-44 months). The median
      OS and PFS were 21 and 14 months, respectively. The median LRFS time was not
      reached. The 2-year LRFS, OS and PFS were 62.5%, 45.1% and 28.0%, respectively.
      Two patients experienced Grade 3 treatment-related pneumonitis, two patients
      experienced Grade 5 treatment-related pneumonitis and two patients had >=Grade 3
      oesophagitis. CONCLUSION: SIB-IMRT appears to be an effective therapeutic option
      in patients with LANSCLC and warrants further evaluation with increased number of
      patients in prospective clinical trials. ADVANCES IN KNOWLEDGE: This study
      explores the feasibility of delivering tumoricidal doses of radiation to primary
      lesions in non-small-cell lung cancer.

PMID- 24588669
TI  - Defining normoxia, physoxia and hypoxia in tumours-implications for treatment
      response.
AB  - Tumour hypoxia is increasingly recognized as a major deleterious factor in cancer
      therapies, as it compromises treatment and drives malignant progression. This
      review seeks to clarify the oxygen levels that are pertinent to this issue. It is
      argued that normoxia (20% oxygen) is an extremely poor comparator for "physoxia",
      i.e. the much lower levels of oxygen universally found in normal tissues, which
      averages about 5% oxygen, and ranges from about 3% to 7.4%. Importantly, it
      should be recognized that the median oxygenation in untreated tumours is
      significantly much lower, falling between approximately 0.3% and 4.2% oxygen,
      with most tumours exhibiting median oxygen levels <2%. This is partially
      dependent on the tissue of origin, and it is notable that many prostate and
      pancreatic tumours are profoundly hypoxic. In addition, therapy can induce even
      further, often unrecognized, changes in tumour oxygenation that may vary
      longitudinally, increasing or decreasing during treatment in ways that are not
      always predictable. Studies that fail to take cognizance of the actual
      physiological levels of oxygen in tissues (approximately 5%) and tumours
      (approximately 1%) may fail to identify the real circumstances driving tumour
      response to treatment and/or malignant progression. This can be of particular
      importance in genetic studies in vitro when comparison to human tumours is
      required.

PMID- 24588670
TI  - An arranged marriage for precision medicine: hypoxia and genomic assays in
      localized prostate cancer radiotherapy.
AB  - Prostate cancer (CaP) is the most commonly diagnosed malignancy in males in the
      Western world with one in six males diagnosed in their lifetime. Current clinical
      prognostication groupings use pathologic Gleason score, pre-treatment prostatic
      specific antigen and Union for International Cancer Control-TNM staging to place
      patients with localized CaP into low-, intermediate- and high-risk categories.
      These categories represent an increasing risk of biochemical failure and CaP
      specific mortality rates, they also reflect the need for increasing treatment
      intensity and justification for increased side effects. In this article, we point
      out that 30-50% of patients will still fail image-guided radiotherapy or surgery
      despite the judicious use of clinical risk categories owing to interpatient
      heterogeneity in treatment response. To improve treatment individualization,
      better predictors of prognosis and radiotherapy treatment response are needed to
      triage patients to bespoke and intensified CaP treatment protocols. These should
      include the use of pre-treatment genomic tests based on DNA or RNA indices and/or
      assays that reflect cancer metabolism, such as hypoxia assays, to define patient
      specific CaP progression and aggression. More importantly, it is argued that
      these novel prognostic assays could be even more useful if combined together to
      drive forward precision cancer medicine for localized CaP.

PMID- 24588671
TI  - Evaluation of a synthetic single-crystal diamond detector for relative dosimetry
      measurements on a CyberKnife.
AB  - OBJECTIVE: To evaluate a new commercial PTW-60019 microDiamond (PTW, Freiburg,
      Germany) synthetic single-crystal diamond detector for relative dosimetry
      measurements on a clinical CyberKnifeTM VSI (Accuray Inc., Sunnyvale, CA) system.
      METHODS: Relative output factors (ROFs) were measured for collimator diameters
      from 5 to 60 mm, and compared with diode [PTW-60017, PTW-60018 and IBA Dosimetry
      (Schwarzenbruck, Germany) SFD] and ionization chamber (PTW-31014 PinPoint and PTW
      31010 Semiflex) measurements. Beam profiles were measured at a range of depths,
      and collimator sizes, with the detector stem oriented both parallel and
      perpendicular to the central axis (CAX). Percentage depth-dose (PDD) curves were
      obtained for the 60-mm collimator and compared with natural Diamond Detector (PTW
      60003) and ionization chamber curves to evaluate energy dependence. RESULTS:
      Penumbral broadening was noted on profile measurements made with the microDiamond
      oriented with the stem parallel to the CAX, in comparison with diodes. Oriented
      perpendicular to the CAX, the profile penumbra was sharper, but stem effects
      could not be ruled out. The PDD measurements were within 0.5% of ionization
      chamber measurements, indicating insignificant dose-rate dependence. The ROF for
      the microDiamond fell between diode and ionization chamber results. Published
      Monte Carlo-derived CyberKnife-specific factors were applied to the PTW-60017,
      PTW-60018 and PTW-31014 ROFs, and the microDiamond factors agreed within 2.0% of
      the mean of these. CONCLUSION: Over a range of small field relative dosimetry
      measurements, the microDiamond detector shows excellent spatial resolution, dose
      rate independence and water equivalence. ADVANCES IN KNOWLEDGE: The microDiamond
      is a suitable tool for commissioning stereotactic systems.

PMID- 24588672
TI  - BJR radiobiology special feature.

PMID- 24588675
TI  - Phase-contrast CT: qualitative and quantitative evaluation of atherosclerotic
      carotid artery plaque.
AB  - PURPOSE: To evaluate the potential of phase-contrast computed tomography (CT) for
      atherosclerotic plaque imaging in human carotid arteries in an experimental ex
      vivo study. MATERIALS AND METHODS: The study was approved by the institutional
      review board, and informed consent was obtained from the patients' relatives.
      Seven postmortem human carotid artery specimens were imaged at a laboratory setup
      by using a conventional x-ray tube and grating interferometer. After histologic
      processing, phase-contrast imaging and histopathologic data were matched.
      Characteristics of the necrotic core (NC) covered by a fibrous cap (FC),
      intraplaque hemorrhage (IPH), and calcifications (CAs) were established, and
      sensitivity, specificity, and accuracy of phase-contrast CT for plaque detection
      and the potential for accurate quantification were assessed. The Cohen kappa and
      Pearson correlation coefficient R were used to determine the agreement between
      phase-contrast imaging and histopathologic findings for plaque characterization
      and correlation of quantitative plaque measurements, respectively. A difference
      with a P value of less than .05 was considered significant. RESULTS:
      Characteristic criteria were found in all analyzed plaque components. Applying
      these criteria, phase-contrast CT had a good sensitivity for the detection of the
      FC and NC, IPH, and CAs (all, >80%) and excellent specificity and accuracy (all,
      >90%), with good interreader agreement (kappa >= 0.72, P < .0001). There were
      excellent correlations for quantitative measurements of FC, NC, and CAs between
      phase-contrast imaging and histopathologic findings (R >= 0.92). Interreader
      reproducibility was excellent, with an intraclass correlation coefficient of 0.98
      or higher for all measurements. CONCLUSION: The results of this study indicate
      that ex vivo phase-contrast CT can help identify and quantify atherosclerotic
      plaque components, with excellent correlation to histopathologic findings.
      Although not yet applicable in vivo, phase-contrast CT may become a valuable tool
      to monitor atherosclerotic disease process noninvasively.

PMID- 24588676
TI  - Generalized tonic-clonic seizures: aberrant interhemispheric functional and
      anatomical connectivity.
AB  - PURPOSE: To characterize interhemispheric functional and anatomic connectivity in
      patients with idiopathic generalized epilepsy and generalized tonic-clonic
      seizures (GTCS). MATERIALS AND METHODS: This retrospective study was approved by
      the local institutional review board and was HIPAA compliant. All participants
      provided written informed consent. Resting-state functional and structural
      magnetic resonance images were acquired in 52 patients with GTCS and 65 healthy
      control subjects. The functional connectivity between bilateral homotopic voxels
      was calculated. Homotopic regions showing abnormal functional connectivity in
      patients were adopted as regions of interest for an analysis of diffusion-tensor
      imaging tractography. The fractional anisotropy and fiber length were compared
      between groups. Two-sample t test and nonparametric correlation analysis were
      used. RESULTS: Compared with control subjects, patients showed increased
      interhemispheric functional connectivity between the bilateral cuneus (P = .0008,
      corrected) and anterior cingulate cortex (P = .0003, corrected) and decreased
      functional connectivity between the bilateral olfactory cortex (P = .00005,
      corrected), inferior frontal gyrus (P = .00005, corrected), supramarginal gyrus
      (P = .0002, corrected), and temporal pole (P = .0003, corrected). Furthermore,
      the fiber length of the commissural fiber bundles connecting the bilateral
      anterior cingulate cortex (t = -2.30; P = .03, uncorrected) and the bilateral
      cuneus was shorter in patients than in control subjects (t = -3.19; P = .002,
      uncorrected). CONCLUSION: Our findings show that the bilateral anterior cingulate
      cortex may be critical to the pathophysiology of patients with GTCS and suggest
      that the corresponding commissural fiber bundle in the genu of the corpus
      callosum is a potential target for future surgical treatment in patients with
      intractable GTCS.

PMID- 24588677
TI  - Small (<=1-cm) hepatocellular carcinoma: diagnostic performance and imaging
      features at gadoxetic acid-enhanced MR imaging.
AB  - PURPOSE: To assess diagnostic performance and imaging features of gadoxetic acid
      enhanced magnetic resonance (MR) imaging in small (<=1-cm) hepatocellular
      carcinoma (HCC) detection in patients with chronic liver disease. MATERIALS AND
      METHODS: The institutional review board approved this retrospective study and
      waived informed consent. Sixty patients (56 men, four women; mean age, 60.1
      years) with HCC (146 lesions; 70 > 1 cm, 76 <= 1 cm) underwent gadoxetic acid
      enhanced MR imaging. HCC was confirmed at surgical resection (72 lesions; 30 > 1
      cm, 42 <= 1 cm) or by showing interval growth with typical enhancement patterns
      at follow-up dynamic computed tomography or MR imaging (74 lesions; 40 > 1 cm, 34
      <= 1 cm). Two radiologists assessed MR imaging features and graded likelihood of
      HCC with a five-point confidence scale. Jackknife alternative free-response
      receiver operating characteristic (JAFROC) method was used. RESULTS: Mean JAFROC
      figure of merit for small HCC was 0.717; that for large (>1-cm) HCC was 0.973
      with substantial agreement (kappa = 0.676). Mean sensitivity and positive
      predictive value (PPV) were 46.0% (70 of 152) and 48.3% (70 of 145) for small HCC
      versus 95.0% (133 of 140) and 78.2% (133 of 170) for large HCC, respectively.
      Eleven of 76 small HCCs (14%) were not seen on MR images, even after careful
      investigation. MR imaging features of small HCC included arterial enhancement
      (79%, 60 of 76), hypointensity on hepatobiliary phase (HBP) images (68%, 52 of
      76), washout on 3-minute delayed phase images (50%, 38 of 76), hyperintensity on
      T2-weighted images (43%, 33 of 76), hypointensity on T1-weighted images (32%, 24
      of 76), and restriction on diffusion-weighted images (28%, 20 of 72). Arterial
      enhancement and washout on 3-minute delayed phase images or hypointensity on HBP
      images occurred in 66% of small HCCs (50 of 76). CONCLUSION: Diagnostic
      performance of gadoxetic acid-enhanced MR imaging for small HCC detection is
      still low, with mean sensitivity of 46.0% (70 of 152) and mean PPV of 48.3% (70
      of 145). By adding hypointensity on HBP images as washout, diagnostic performance
      for small HCC detection can be improved.

PMID- 24588674
TI  - Uncoupling protein-2 mediates the protective action of berberine against
      oxidative stress in rat insulinoma INS-1E cells and in diabetic mouse islets.
AB  - BACKGROUND AND PURPOSE: Uncoupling protein-2 (UCP2) may regulate glucose
      stimulated insulin secretion. The current study investigated the effects of
      berberine, an alkaloid found in many medicinal plants, on oxidative stress and
      insulin secretion through restoration of UCP2 expression in high glucose (HG)
      treated INS-1E cells and rat islets or in db/db mouse islets. EXPERIMENTAL
      APPROACH: Mouse and rat pancreatic islets were isolated. Nitrotyrosine,
      superoxide dismutase (SOD)-1 and UCP2 expression and AMPK phosphorylation were
      examined by Western blotting. Insulin secretion was measured by ELISA.
      Mitochondrial reactive oxygen species (ROS) production was detected by confocal
      microscopy. KEY RESULTS: Incubation of INS-1E cells and rat islets with HG (30
      mmol.L(-1); 8 h) elevated nitrotyrosine level, reduced SOD-1 and UCP2 expression
      and AMPK phosphorylation, and inhibited glucose-stimulated insulin secretion. HG
      also increased mitochondrial ROS in INS-1E cells. Co-treatment with berberine
      inhibited such effects. The AMPK inhibitor compound C, the UCP2 inhibitor genipin
      and adenovirus ucp2 shRNA inhibited these protective effects of berberine.
      Furthermore, compound C normalized berberine-stimulated UCP2 expression but
      genipin did not affect AMPK phosphorylation. Islets from db/db mice exhibited
      elevated nitrotyrosine levels, reduced expression of SOD-1 and UCP2 and AMPK
      phosphorylation, and decreased insulin secretion compared with those from db/m(+)
      mice. Berberine also improved these defects in diabetic islets and genipin
      blocked the effects of berberine. CONCLUSIONS AND IMPLICATIONS: Berberine
      inhibited oxidative stress and restored insulin secretion in HG-treated INS-IE
      cells and diabetic mouse islets by activating AMPK and UCP2. UCP2 is an important
      signalling molecule in mediating anti-diabetic effects of berberine.

PMID- 24588678
TI  - SVM classification and CoMSIA modeling of UGT1A6 interacting molecules.
AB  - The human UDP-glucuronosyltransferase 1A6 (UGT1A6) plays important roles in
      elimination of many xenobiotics, including drugs. We have experimentally assessed
      inhibitory properties of 46 compounds toward UGT1A6 catalyzing the
      glucuronidation of 1-naphthol and built models for predicting compounds
      interactions with the enzyme. The tested compounds were divided into a training
      set (n = 31; evaluated by 10-fold cross-validation) and an external test set (n =
      15), both of which yielded similar accuracies (80-81%) and Matthews correlation
      coefficients (0.61-0.63) when classified using support vector machines.
      Comparative molecular similarity index analysis (CoMSIA) modeling was conducted
      for nine methods of compound alignment. The most predictive CoMSIA model was
      analyzed in the light of a homology modeled UGT1A6 structure, with leave-one-out
      cross-validation, yielding a q2 of 0.62 and r2 of 0.91 on the training set and a
      r2(pred) of 0.82 on the test set. The CoMSIA contour plots highlighted the
      importance of H-bond donors and electrostatic field interactions, accounting for
      28% and 25% contribution of the model, respectively.

PMID- 24588679
TI  - Using structured telephone follow-up assessments to improve suicide-related
      adverse event detection.
AB  - Adverse event (AE) detection and reporting practices were compared during the
      first phase of the Emergency Department Safety Assessment and Follow-up
      Evaluation (ED-SAFE), a suicide intervention study. Data were collected using a
      combination of chart reviews and structured telephone follow-up assessments
      postenrollment. Beyond chart reviews, structured telephone follow-up assessments
      identified 45% of the total AEs in our study. Notably, detection of suicide
      attempts significantly varied by approach with 53 (18%) detected by chart review,
      173 (59%) by structured telephone follow-up assessments, and 69 (23%) marked as
      duplicates. Findings provide support for utilizing multiple methods for more
      robust AE detection in suicide research. 

PMID- 24588680
TI  - Metabolic engineering of volatile isoprenoids in plants and microbes.
AB  - The chemical properties and diversity of volatile isoprenoids lends them to a
      broad variety of biological roles. It also lends them to a host of
      biotechnological applications, both by taking advantage of their natural
      functions and by using them as industrial chemicals/chemical feedstocks. Natural
      functions include roles as insect attractants and repellents, abiotic stress
      protectants in pathogen defense, etc. Industrial applications include use as
      pharmaceuticals, flavours, fragrances, fuels, fuel additives, etc. Here we will
      examine the ways in which researchers have so far found to exploit volatile
      isoprenoids using biotechnology. Production and/or modification of volatiles
      using metabolic engineering in both plants and microorganisms are reviewed,
      including engineering through both mevalonate and methylerythritol diphosphate
      pathways. Recent advances are illustrated using several case studies (herbivores
      and bodyguards, isoprene, and monoterpene production in microbes). Systems and
      synthetic biology tools with particular utility for metabolic engineering are
      also reviewed. Finally, we discuss the practical realities of various
      applications in modern biotechnology, explore possible future applications, and
      examine the challenges of moving these technologies forward so that they can
      deliver tangible benefits. While this review focuses on volatile isoprenoids,
      many of the engineering approaches described here are also applicable to non
      isoprenoid volatiles and to non-volatile isoprenoids. 

PMID- 24588681
TI  - In vitro hypercoagulability on whole blood thromboelastometry associated with in
      vivo reduction of circulating red cell mass in dogs.
AB  - BACKGROUND: Previous studies have reported a strong correlation between
      indicators of red cell mass (RCM) and thromboelastometry results (TEM) in several
      species, specifically an association of apparent hypercoagulability with
      decreased RCM. OBJECTIVES: The objectives of the study were to (1) evaluate the
      effect of decreased circulating RCM on TEM results in dogs, and (2) determine the
      relative contributions of citrate dilution vs in vivo reduction of RCM to
      hemostatic potential. MATERIALS AND METHODS: Thirteen healthy dogs had one unit
      of blood removed on day 0. Whole blood, EDTA, and citrated blood samples for
      evaluation of TEM variables and PT, APTT, platelet count, fibrinogen, thrombin
      antithrombin (TAT), and thrombin generation were collected at baseline, and 3 and
      21 days after blood removal. Blood samples were also corrected to a PCV of 45% by
      adding citrate or removing plasma. RESULTS: On day 3 after blood removal, the PCV
      was significantly decreased (45 +/- 6%) compared with baseline (52 +/- 6%) and
      day 21 (50 +/- 4%, P < .001), accompanied by TEM variables indicating
      hypercoagulability, which returned to baseline values by day 21. Other
      coagulation variables such as PT, APTT, platelet count, TAT, or plasma thrombin
      generation remained unchanged, with the exception of fibrinogen that was
      significantly higher on day 3. No changes were related to citrate dilution.
      CONCLUSIONS: Transiently decreased RCM in vivo was accompanied by TEM variables
      indicating hypercoagulability, which was not confirmed by other coagulation
      variables. This suggests an artifact of TEM, which presents a potential
      limitation of this technology in patient populations with abnormal RCM.

PMID- 24588682
TI  - Synthesis and characterization of iron trisphenolate complexes with hydrogen
      bonding cavities.
AB  - A new family of C3-symmetric ligands, featuring phenolate donors and a secondary
      coordination sphere, have been synthesized. We report the synthesis and
      subsequent coordination chemistry of these new tripodal N-anchored
      tris(phenolate) chelates, [tris(5-tert-butyl-3-N-carboxamide-2
      hydroxybenzyl)amines] (H3(R)SalAmi), to iron(II), iron(III), and zinc(II). These
      electron-rich complexes have intramolecular hydrogen bonds, and therefore the
      potential to stabilize biologically relevant substrates in small-molecule
      activation chemistry. 

PMID- 24588683
TI  - Characteristics of asthmatic patients with and without repeat emergency
      department visits at an inner city hospital.
AB  - Abstract Objective: The objective of this study was to document the frequency and
      clinical characteristics associated with repeat emergency department (ED) visits
      for asthma in an inner city population with a high burden of asthma. METHODS:
      During an ED visit for asthma in an inner city hospital ('index visit'), patients
      completed a valid survey addressing disease and behavioral factors. Hospital
      records were reviewed for information about ED visits and hospitalizations for
      asthma during the 12 months before and the 90 days after the index visit.
      RESULTS: One hundred and ninety-two patients were enrolled; the mean age was 42
      years, 69% were women, 36% were black, 54% were Latino, 69% had Medicaid, and 17%
      were uninsured. 100 patients (52%) were treated and released from the ED, 88
      patients (46%) were hospitalized, and 4 patients (2%) left against medical
      advice. During the subsequent 90 days, 64 patients (33%) had at least one repeat
      ED visit for asthma and 27 (14%) were hospitalized for asthma. In a multivariate
      model, more past ED visits (OR 1.7, 95% CI 1.4, 2.1; p < 0.0001) and male gender
      (OR 2.5, 95% CI 1.2, 5.4; p = 0.02) remained associated with having a repeat ED
      visit. Most patients had the first repeat ED visit within 30 days and 18 returned
      within only 7 days. Among all patients with a repeat visit, those who were not
      hospitalized for the index visit were more likely to have a repeat visit within 7
      days (37%) compared to those who were hospitalized (17%) (p = 0.05 in
      multivariate analysis). CONCLUSIONS: Repeat ED visits were prevalent among inner
      city asthma patients and most occurred shortly after the index visit. The
      strongest predictors of repeat visits were male gender and more ED visits in the
      12 months before the index visit.

PMID- 24588684
TI  - Publication date and author spelling for the hidden angelshark Squatina occulta.
AB  - Two dates of publication have been associated with the hidden angelshark Squatina
      occulta. Additionally, the name of the second author of this species has been
      cited with different spellings in different publications. Both inconsistencies
      are addressed in this study. It is suggested that the hidden angelshark be
      consistently cited as Squatina occulta Vooren & da Silva 1991. 

PMID- 24588685
TI  - Acceptability of early integration of palliative care in patients with incurable
      lung cancer.
AB  - BACKGROUND: Lung cancer remains the leading cause of cancer death, and it is
      known many affected will have significant palliative care needs. Evidence
      suggests that early involvement of palliative care can translate into
      improvements in quality of care, quality of life, and survival. However, routine
      early integration is yet to be embraced as standard of care for the majority of
      patients, and it is unclear what lung cancer clinicians continue to perceive as
      the barriers to this model of care. METHODS: We performed a qualitative
      exploration of lung cancer clinicians' perceptions, focusing on current
      experiences of engaging with palliative care, perceptions of palliative care for
      patients with lung cancer, and views of barriers and benefits of referring to
      palliative care. RESULTS: Focus group and targeted interviews were conducted with
      28 clinicians, with four key emergent themes: 1) Competence/skill--with referrers
      needing to be confident in the quality and capability of palliative care
      provision; 2) Care Coordination--the need to ensure integrated care, with defined
      lines of responsibility and clear team communication; 3) Ease of referral--the
      need for ready access to a palliative care provider in the lung cancer clinic;
      and 4) Perceptions--concerns about loss of hope and fears of negative patient
      reaction. CONCLUSIONS: Early and routine involvement of palliative care in
      patients with incurable lung cancer is acceptable to the majority of treating
      clinicians. To facilitate early integration of palliative care, palliative care
      providers need to become front-line team members who provide a high-quality
      service. Lung cancer clinicians need further education as to the role and
      benefits of early palliative care, and how best to introduce this.

PMID- 24588686
TI  - Unique lead adsorption behavior of activated hydroxyl group in two-dimensional
      titanium carbide.
AB  - The functional groups and site interactions on the surfaces of two-dimensional
      (2D) layered titanium carbide can be tailored to attain some extraordinary
      physical properties. Herein a 2D alk-MXene (Ti3C2(OH/ONa)(x)F(2-x)) material,
      prepared by chemical exfoliation followed by alkalization intercalation, exhibits
      preferential Pb(II) sorption behavior when competing cations (Ca(II)/Mg(II))
      coexisted at high levels. Kinetic tests show that the sorption equilibrium is
      achieved in as short a time as 120 s. Attractively, the alk-MXene presents
      efficient Pb(II) uptake performance with the applied sorption capacities of 4500
      kg water per alk-MXene, and the effluent Pb(II) contents are below the drinking
      water standard recommended by the World Health Organization (10 MUg/L).
      Experimental and computational studies suggest that the sorption behavior is
      related to the hydroxyl groups in activated Ti sites, where Pb(II) ion exchange
      is facilitated by the formation of a hexagonal potential trap.

PMID- 24588688
TI  - Activation of toll-like receptors alters the microRNA expression profile of
      keratinocytes.
AB  - Keratinocytes recognize invading pathogens by various receptors, among them Toll
      like receptors (TLRs), and provide the first line of defense in skin immunity.
      The role of microRNAs in this important defense mechanism has not been explored
      yet. Our aim was to identify microRNAs involved in the innate immune response of
      keratinocytes. MicroRNA expression profiling revealed that the TLR2 ligand
      zymosan, the TLR3 ligand poly(I:C) or the TLR5 ligand flagellin significantly
      altered the microRNA expression in keratinocytes. The regulation of microRNAs was
      concentration-dependent and it could be neutralized by siRNAs specific for TLR2,
      TLR3 and TLR5, respectively, confirming the specificity of the TLR response.
      Interestingly, one microRNA, miR-146a, was strongly induced by all studied TLR
      ligands, while other microRNAs were regulated in a TLR- or time point-specific
      manner. These findings suggest an important role for microRNAs in the innate
      immune response of keratinocytes and provide a basis for further investigations. 

PMID- 24588687
TI  - Dietary exposure of Hong Kong adults to pesticide residues: results of the first
      Hong Kong Total Diet Study.
AB  - The use of pesticides and other chemicals has become a common practice in modern
      agriculture to enhance and stabilise crop yield, protect the nutritional
      integrity of food, facilitate food storage to assure year-round supplies, and
      provide attractive and appealing food products. With the adoption of strict good
      agricultural practice (GAP), only minimal amounts of pesticide residues should
      remain on the crops or in connected foods of animal origin up the food chain. To
      assess their associated health risk to local people, the dietary exposure of Hong
      Kong adults to residues of four groups of pesticides or their metabolites -
      organophosphorus pesticides (OPPs), carbamates, pyrethrins and pyrethroids, and
      dithiocarbamate (DTC) metabolites - is estimated in the first Hong Kong Total
      Diet Study (TDS). A total of 150 commonly consumed food items were collected and
      prepared "as consumed". A total of 600 composite food samples were analysed for
      85 pesticides or their metabolites by liquid chromatography-tandem mass
      spectrometry (LC-MS/MS). These pesticides were primarily found at low levels
      (highest mean = 350 MUg kg-1) in food samples of plant origin such as vegetables
      and fruits. Dietary exposures to pesticide residues were estimated based on the
      analytical results and the food consumption data of the local residents. The
      estimated dietary exposures of Hong Kong adults to all individual pesticides were
      well below their respective acceptable daily intakes (ADIs). The percentage
      contributions of the estimated mean and 95th percentile dietary exposures to the
      ADIs of individual pesticides were <6% and <24% for the OPPs, <1% for the
      carbamates and pyrethrins and pyrethroids, and <1% and <4% for the DTC
      metabolites, respectively. The findings indicate that dietary exposures to all
      the pesticide residues analysed in this study were unlikely to pose unacceptable
      health risks to the Hong Kong population.

PMID- 24588689
TI  - Quantification of ocular biologically effective UV exposure for different
      rotation angle ranges based on data from a manikin.
AB  - Human outdoor activities are randomly orientated at different angles to the sun.
      To quantify the ocular UV and biologically effective UV (UVBE; i.e. the ocular UV
      irradiance exposure for photokeratitis (UVpker), photoconjunctivitis (UVpcon),
      and cataract (UVcat)) exposure for different rotation angle ranges, a rotating
      manikin was used to monitor the ocular UV exposure at different rotation angles
      in clear skies during July 2010 in Sanya, China. As a result, the ocular UV and
      UVBE irradiance was directly influenced by the rotation angle variations,
      primarily for the 120 degrees  rotation angle ranges facing the morning and
      afternoon sun when the solar elevation was lower than 60 degrees ; during these
      times, the UV and UVBE spectral irradiance decreased as the rotation angle
      increased. When compared to the 360 degrees  rotation angle ranges (which were
      considered to be the average exposure situation), the cumulative ocular UVBE for
      60 degrees , 120 degrees  and 180 degrees  rotation angle ranges were maximally
      91% (UVcat), 94% (UVpker) and 121% (UVpcon); 71% (UVcat), 74% (UVpker) and 95%
      (UVpcon); 42%(UVcat), 45%(UVpker) and 55% (UVpcon) higher respectively.
      Meanwhile, the cumulative ocular UVBE for the 180 degrees  rotation angle ranges
      facing away from the sun were 46% (UVpker), 59% (UVpcon) and 45% (UVcat) lower. 

PMID- 24588690
TI  - Highly elevated serum concentrations of perfluoroalkyl substances in fishery
      employees from Tangxun lake, china.
AB  - Increasing production and use of per- and polyfluoroalkyl substances (PFASs) has
      been reported from China, and a few studies have shown there are subpopulations
      in China with high and increasing exposure to these chemicals. In this paper, we
      present a comprehensive exposure assessment of PFASs in fishery employees from
      Tangxun Lake, China. Exceptionally high serum concentrations of C4 to C12 PFASs
      were observed in fishery employees (n = 39, median perfluorooctanesulfonic acid
      (PFOS) 10 400 ng/mL) compared to a reference group from the same city (n = 9,
      median PFOS 18.7 ng/mL). On the basis of the comparison of different exposure
      pathways, it was concluded that contaminated fish from Tangxun Lake was the
      primary source of PFAS exposure to fishery employees, and there was a positive
      association between serum PFAS concentrations and time of employment in the
      fishery. PFOS isomer profiles in fishery employees showed a significantly higher
      proportion of linear PFOS (78.4%) compared to the background-exposed reference
      group (66.8%), reflecting the highly linear PFOS isomer profile (>90%) of lake
      fish. Median renal clearance rates (CLrenal) of C4 to C10 perfluoroalkyl
      carboxylic acids (PFCAs) and perfluoroalkanesulfonic acids (PFSAs) ranged from
      0.020 to 16.5 mL/day/kg and 0.013 to 9.43 mL/day/kg, respectively. PFCAs with
      less than eight perfluoroalkyl carbons were primarily eliminated via urine,
      whereas other routes of excretion may have contributed to the elimination for
      long-chain PFCAs and PFSAs. Calculated daily PFOS exposures of fishery employees
      significantly exceeded tolerable daily intake limits, but clinical blood
      chemistry parameters were mostly within normal reference ranges. However,
      additional epidemiological studies are needed to address potential associations
      between PFAS exposure and health effects in the Tangxun Lake area. 

PMID- 24588691
TI  - Evaluation of anti-Mullerian hormone in the first trimester as a predictor for
      hypertensive disorders of pregnancy and other adverse pregnancy outcomes.
AB  - BACKGROUND: Prediction of pre-eclampsia and adverse pregnancy outcomes with
      biomarkers has been proposed. AMH is an ovary-specific growth factor, used to
      predict ovarian reserve, which changes with age similar to the change in age
      related fertility. AIMS: The aim of the study was to determine whether AMH tested
      in the first trimester of pregnancy was associated with pregnancy hypertension or
      adverse pregnancy outcomes. MATERIALS AND METHODS: Retrospective cohort study of
      women who delivered singleton fetuses >=20 weeks' gestation at Royal Hospital for
      Women, Sydney, Australia (n = 331). AMH was tested in 2011 via Beckman-Coulter
      Gen II ELISA method on frozen serum collected at the time of first trimester
      aneuploidy screening (10-13 + 6 weeks' gestation). Outcome data were obtained
      from the hospital database (ObstetriX). Main outcome measures were pregnancy
      hypertension (pre-eclampsia and gestational hypertension) and composite adverse
      pregnancy outcome. RESULTS: The median AMH level was 9.7 pmol/L (interquartile
      range (IQR) 3.9-17.3). There was a trend towards women with pregnancy
      hypertension having lower AMH levels than women without pregnancy hypertension
      (median 5.1 pmol/L, IQR 1.5-13.2 vs 9.4 IQR 3.9-17.3; P = 0.06). After adjusting
      for BMI >=25, parity >=1 and age >=35, women with an AMH less than the 10th
      centile had a 3.3-fold increased risk of pregnancy hypertension (OR 3.3, 95% CI
      1.2-8.7, P = 0.01). There were no other associations between low AMH
      concentration and adverse maternal or neonatal outcomes. CONCLUSIONS: Women with
      a very low AMH (1.5 pmol/L) in early pregnancy may have an increased risk of
      pregnancy hypertension. No other adverse pregnancy outcomes were identified.

PMID- 24588693
TI  - Effect of quercetin on cadmium fluoride-induced alterations in
      hydroxyproline/collagen content in mice liver.
AB  - PURPOSE/AIM OF THE STUDY: To study the effect of quercetin, a flavanoid on
      cadmium fluoride-induced alterations in hydroxyproline and collagen content in
      mice liver. MATERIALS AND METHODS: Following experimental groups were studied:
      Group 1, normal mice; Group 2, CdF2-treated mice administered single
      intraperitoneal (i.p.) injections of CdF2 1 mg/kg bw (body weight); Group 3, CdF2
      treated mice administered single i.p. injections of CdF2 2 mg/kg bw; Group 4,
      mice-injected i.p. with 100 mg quercetin/kg bw; and Group 5, mice-injected i.p.
      with 100 mg quercetin/kg bw followed by 2 mg CdF2/kg bw after 2 h. Mice were
      sacrificed 24 h after CdF injection by asphyxiation with carbon dioxide. RESULTS:
      1 mg/kg and 2 mg/kg body weight (bw) of CdF2 caused a significant increase in
      hepatic total Hyp and collagen when compared with the liver of control mice. This
      was associated with significant changes in free, peptide bound, and protein bound
      Hyp fraction in the livers of treated mice. Quercetin treatment alone and with
      CdF2 also caused a significant increase in total Hyp and total collagen in mice
      liver. CONCLUSION: We conclude that quercetin has a synergestic effect with CdF2
      on the total Hyp and collagen content in mice liver.

PMID- 24588692
TI  - Correlates of psychological distress in study partners of older people with and
      without mild cognitive impairment (MCI) - the Sydney Memory and Ageing Study.
AB  - OBJECTIVES: Psychological effects of supporting someone with mild cognitive
      impairment (MCI) are often overlooked. We aimed to establish correlates of
      psychological distress in study partners of individuals with and without
      nonclinical MCI. METHODS: Demographic, psychosocial and health measures were
      obtained cross-sectionally from 714 participants (39% MCI) and study partners of
      a longitudinal community-based study on cognitive aging. Study partners (i.e.
      family members/friends) were categorized as providing support with instrumental
      everyday activities or not. Psychological distress was measured by the Kessler
      psychological distress scale. Multiple hierarchical regressions examined
      determinants of psychological distress within Pearlin's stress process model.
      RESULTS: Psychological distress was generally low and not associated with MCI or
      whether study partners provided support or not. Instead, distress was greater if
      participants were male irrespective of study partners' sex and if study partners
      reported negative reactions to participants' behavioral symptoms, felt burdened
      by providing support and showed worse coping abilities; overall explaining 37%
      variance. Self-rated disability and aspects of health-related quality of life
      explained additional 7%. CONCLUSION: Objective impairment measures were not
      associated with distress in partners or supporters. However, study partners'
      appraisals of functional and behavioral symptoms were linked to increased
      distress even in this very mildly affected community cohort.

PMID- 24588694
TI  - Using risk model judgements to better understand perceptions of synergistic
      risks.
AB  - Numerous scientific studies show that risk factors can interact to
      synergistically increase the likelihood of certain adverse and life-threatening
      outcomes. Yet, the extent to which individuals know that specific risk factor
      combinations present 'synergistic risks' is unclear and little is known about the
      determinants of such knowledge. This is largely because epistemological progress
      concerning this topic has been frustrated by a reliance on metrics that have
      latterly been judged to be of questionable validity. To address this issue, this
      paper presents two studies that assess an alternative approach (i.e., risk model
      judgements) which requires respondents to judge the risk for a factor combination
      relative to, rather than in isolation from, the risk attributable to each
      constituent factor. Results from both studies indicate that risk model judgements
      overcome the drawbacks of traditional metrics. More importantly, the results
      provide epistemological insights into what can determine whether an individual
      understands that a factor combination presents a synergistic risk; these
      determinants include experiential and intuitive insights into the effects of
      combining specific risk factors, domain-specific judgemental experience and
      exposure to effective learning opportunities. These findings can be utilized in
      interventions aimed at helping individuals to make better decisions concerning
      multiple risk factors. 

PMID- 24588695
TI  - Icotinib: activity and clinical application in Chinese patients with lung cancer.
AB  - INTRODUCTION: Icotinib (BPI-2009H, Conmana) is a novel oral quinazoline compound
      that has proven survival benefit in Chinese patients with lung cancer, for which
      several therapies are currently available often with unsatisfactory results.
      Icotinib is the first self-developed small molecular drug in China for targeted
      therapy of lung cancer. AREAS COVERED: The authors' experience in the clinical
      application of icotinib is reviewed in combination with related publications in
      the literature. Antitumor activities were observed in non-small-cell lung cancer
      and others in several recent studies. On 7 June 2011, icotinib was approved by
      the State Food and Drug Administration of China for the treatment of local
      advanced or metastatic non-small-cell lung cancer based on the results of a
      nationwide, of 27 centers, randomized, double-blind, double-modulated, parallel
      controlled, Phase III trial with single agent icotinib in lung cancer patients
      after failure of chemotherapy. EXPERT OPINION: Icotinib is a generic drug.
      Compared to the other two commercially available EGFR tyrosine kinase inhibitors,
      gefitinib and erlotinib, icotinib is similar to them in chemical structure,
      mechanism of activity and therapeutic effects but less expensive. Better safety
      as well as a wider therapeutic window has also been proven in several Chinese
      studies. Future studies on cost effectiveness are warranted.

PMID- 24588696
TI  - Unusual stacking variations in liquid-phase exfoliated transition metal
      dichalcogenides.
AB  - Liquid-phase exfoliation of layered materials offers a large-scale approach
      toward the synthesis of 2D nanostructures. Structural properties of materials can
      however change during transition from bulk to the 2D state. Any such changes must
      be examined and understood for successful implementation of 2D nanostructures. In
      this work, we demonstrate nonbulk stacking sequences in the few-layer MoS2 and
      WS2 nanoflakes produced by liquid-phase exfoliation. Our analysis shows that
      nonbulk stacking sequences can be derived from its bulk counterparts by
      translational shifts of the layers. No structural changes within the layers were
      observed. Twenty-seven MoS2 and five WS2 nanoflakes were imaged and analyzed.
      Nine MoS2 and four WS2 nanoflakes displayed nonbulk stacking. Such dominance of
      the nonbulk stacking suggests high possibility of unusual stacking sequences in
      other 2D nanostructures. Notably, the electronic structure of some non bulk
      stacked bilayers presents characteristics which are uncommon to either the bulk
      phase or the single monolayer, for instance, a spin-split conduction band bottom.
      Our main characterization technique was annular dark-field scanning transmission
      electron microscopy, which offers direct and reliable imaging of atomic columns.
      The stacking characterization approach employed here can be readily applied
      toward other few-layer transition metal chalcogenides and oxides. 

PMID- 24588697
TI  - What is your diagnosis? Fecal smear stained with Lugol's solution and Giemsa from
      a cynomolgus macaque (Macaca fascicularis) presenting with liquid diarrhea.

PMID- 24588698
TI  - Working memory and intraindividual variability as neurocognitive indicators in
      ADHD: examining competing model predictions.
AB  - OBJECTIVE: The current study examined competing predictions of the default mode,
      cognitive neuroenergetic, and functional working memory models of attention
      deficit/hyperactivity disorder (ADHD) regarding the relation between
      neurocognitive impairments in working memory and intraindividual variability.
      METHOD: Twenty-two children with ADHD and 15 typically developing children were
      assessed on multiple tasks measuring intraindividual reaction time (RT)
      variability (ex-Gaussian: tau, sigma) and central executive (CE) working memory.
      Latent factor scores based on multiple, counterbalanced tasks were created for
      each construct of interest (CE, tau, sigma) to reflect reliable variance
      associated with each construct and remove task-specific, test-retest, and random
      error. RESULTS: Bias-corrected, bootstrapped mediation analyses revealed that CE
      working memory accounted for 88% to 100% of ADHD-related RT variability across
      models, and between-group differences in RT variability were no longer detectable
      after accounting for the mediating role of CE working memory. In contrast, RT
      variability accounted for 10% to 29% of between-group differences in CE working
      memory, and large magnitude CE working memory deficits remained after accounting
      for this partial mediation. Statistical comparison of effect size estimates
      across models suggests directionality of effects, such that the mediation effects
      of CE working memory on RT variability were significantly greater than the
      mediation effects of RT variability on CE working memory. CONCLUSIONS: The
      current findings question the role of RT variability as a primary neurocognitive
      indicator in ADHD and suggest that ADHD-related RT variability may be secondary
      to underlying deficits in CE working memory.

PMID- 24588699
TI  - Predicting decline in mild cognitive impairment: a prospective cognitive study.
AB  - OBJECTIVE: The primary aim of this study was to identify cognitive tests that
      differentiate between persons with mild cognitive impairment (MCI) who later
      develop cognitive decline and those who remain stable. METHOD: This study used a
      prospective longitudinal design. One hundred twenty-two older adults with single
      domain or multiple-domain amnestic MCI were recruited from memory clinics. They
      completed tests to measure baseline episodic memory, working memory, executive
      functions, perception, and language. They were then followed annually to
      determine with criteria independent from those tests whether they had remained
      stable or had developed dementia or significant cognitive decline. This was used
      as the reference standard to measure diagnostic test accuracy value. RESULTS:
      ANOVAs indicated that participants with progressive MCI showed more impaired
      performance than those with stable MCI at baseline on episodic memory (word and
      story recall), the Brown-Peterson working memory test, object naming, object
      decision, and position of gap test. Logistic regression derived a significant
      model with 87.8% overall predictive value. The model included delayed text
      memory, free recall, naming, orientation match, object decision, and alpha span.
      Its sensitivity was 86.2% and its specificity was 88.9%. Positive predictive
      value was 83.3%, and negative predictive value was particularly high at 90.9%.
      CONCLUSIONS: Identifying individuals with MCI who will progress to dementia or
      more severe cognitive impairment is a challenge. This study shows that cognitive
      measures provide valuable information regarding the predictive diagnosis of
      persons with MCI. Predictive accuracy of a cognitive battery might be optimized
      by selecting both memory and nonmemory measures.

PMID- 24588700
TI  - Developmental gender differences in children in a virtual spatial memory task.
AB  - OBJECTIVE: Behavioral achievements are the product of brain maturation. During
      postnatal development, the medial temporal lobe completes its maturation, and
      children acquire new memory abilities. In recent years, virtual reality-based
      tasks have been introduced in the neuropsychology field to assess different
      cognitive functions. In this work, desktop virtual reality tasks are combined
      with classic psychometric tests to assess spatial abilities in 4- to 10-year-old
      children. METHOD: Fifty boys and 50 girls 4-10-years of age participated in this
      study. Spatial reference memory and spatial working memory were assessed using a
      desktop virtual reality-based task. Other classic psychometric tests were also
      included in this work (e.g., the Corsi Block Tapping Test, digit tests, 10/36
      Spatial Recall Test). RESULTS: In general terms, 4- and 5-year-old groups showed
      poorer performance than the older groups. However, 5-year-old children showed
      basic spatial navigation abilities with little difficulty. In addition, boys
      outperformed girls from the 6-8-year-old groups. Gender differences only emerged
      in the reference-memory version of the spatial task, whereas both sexes displayed
      similar performances in the working-memory version. CONCLUSION: There was general
      improvement in the performance of different tasks in children older than 5 years.
      However, results also suggest that brain regions involved in allocentric memory
      are functional even at the age of 5. In addition, the brain structures underlying
      reference memory mature later in girls than those required for the working
      memory.

PMID- 24588701
TI  - The nature of facial expression recognition deficits following orbitofrontal
      cortex damage.
AB  - OBJECTIVE: Orbitofrontal cortex (OFC) damage has been associated with facial
      expression recognition deficits in some, but not all, previous studies. The
      pattern of performance of a group of patients with OFC damage was assessed across
      a series of facial expression recognition tasks. We aimed to determine whether
      some tasks were more sensitive at detecting deficits than others. METHOD: Seven
      patients with damage to the OFC, 6 control patients with frontal lesions that
      spared the OFC, and a group of healthy controls completed a series of facial
      expression recognition tasks including 2 labeling tasks and 2 matching tasks.
      RESULTS: The OFC patient group demonstrated impaired labeling of negative facial
      expressions (i.e., anger, disgust, fear, and sadness) shown for a short time (500
      ms) relative to the comparison groups. When facial expressions were shown for a
      longer time (5,000 ms), the OFC patient group's performance did not differ
      significantly from either comparison group. The OFC patient group was impaired
      when matching subtle, low intensity negative facial expressions, but not when
      matching high intensity, prototypical facial expressions. CONCLUSIONS: The
      pattern of performance across tasks revealed that only certain facial expression
      recognition tasks appear to be sufficiently sensitive to detect deficits in
      patients with OFC damage. These findings have important implications for the
      assessment of facial expression recognition difficulties in patients with OFC
      damage and more broadly, for special populations.

PMID- 24588702
TI  - Domain-general sequence learning deficit in specific language impairment.
AB  - OBJECTIVE: Grammar-specific accounts of specific language impairment (SLI) have
      been challenged by recent claims that language problems are a consequence of
      impairments in domain-general mechanisms of learning that also play a key role in
      the process of language acquisition. Our studies were designed to test the
      generality and nature of this learning deficit by focusing on both sequential and
      nonsequential, and on verbal and nonverbal, domains. METHOD: Twenty-nine children
      with SLI were compared with age-matched typically developing (TD) control
      children using (a) a serial reaction time task (SRT), testing the learning of
      motor sequences; (b) an artificial grammar learning (AGL) task, testing the
      extraction of regularities from auditory sequences; and (c) a weather prediction
      task (WP), testing probabilistic category learning in a nonsequential task.
      RESULTS: For the 2 sequence learning tasks, a significantly smaller proportion of
      children showed evidence of learning in the SLI than in the TD group (chi2 tests,
      p < .001 for the SRT task, p < .05 for the AGL task), whereas the proportion of
      learners on the WP task was the same in the 2 groups. The level of learning for
      SLI learners was comparable with that of TD children on all tasks (with great
      individual variation). CONCLUSIONS: Taken together, these findings suggest that
      domain-general processes of implicit sequence learning tend to be impaired in
      SLI. Further research is needed to clarify the relationship of deficits in
      implicit learning and language.

PMID- 24588705
TI  - Activation of P2RY11 and ATP release by lipoxin A4 restores the airway surface
      liquid layer and epithelial repair in cystic fibrosis.
AB  - In cystic fibrosis (CF), the airway surface liquid (ASL) height is reduced as a
      result of impaired ion transport, which favors bacterial colonization and
      inflammation of the airway and leads to progressive lung destruction. Lipoxin
      (LX)A4, which promotes resolution of inflammation, is inadequately produced in
      the airways of patients with CF. We previously demonstrated that LXA4 stimulates
      an ASL height increase and epithelial repair. Here we report the molecular
      mechanisms involved in these processes. We found that LXA4 (1 nM) induced an
      apical ATP release from non-CF (NuLi-1) and CF (CuFi-1) airway epithelial cell
      lines and CF primary cultures. The ATP release induced by LXA4 was completely
      inhibited by antagonists of the ALX/FPR2 receptor and Pannexin-1 channels. LXA4
      induced an increase in intracellular cAMP and calcium, which were abolished by
      the selective inhibition of the P2RY11 purinoreceptor. Pannexin-1 and ATP
      hydrolysis inhibition and P2RY11 purinoreceptor knockdown all abolished the
      increase of ASL height induced by LXA4. Inhibition of the A2b adenosine receptor
      did not affect the ASL height increase induced by LXA4, whereas the PKA inhibitor
      partially inhibited this response. The stimulation of NuLi-1 and CuFi-1 cell
      proliferation, migration, and wound repair by LXA4 was inhibited by the
      antagonists of Pannexin-1 channel and P2RY11 purinoreceptor. Taken together, our
      results provide evidence for a novel role of LXA4 in stimulating apical ATP
      secretion via Pannexin-1 channels and P2RY11 purinoreceptors activation leading
      to an ASL height increase and epithelial repair. 

PMID- 24588706
TI  - Basic biology of adeno-associated virus (AAV) vectors used in gene therapy.
AB  - Adeno-associated virus (AAV) based vectors have emerged as important tools for
      gene therapy in humans. The recent successes seen in Phase I/II clinical trials
      have also highlighted the issues related to the host and vector-related immune
      response that preclude the universal application of this promising vector system.
      A fundamental insight into the biological mechanisms by which AAV infects the
      host cell and a thorough understanding of the immediate and long-lived cellular
      responses to AAV infection is likely to offer clues and help design better
      intervention strategies to improve the therapeutic efficiency of AAV vectors.
      This article reviews the biology of AAV-host cellular interactions and outlines
      their application in the development of novel and improved AAV vector systems. 

PMID- 24588707
TI  - MicroRNA pathways: an emerging role in identification of therapeutic strategies.
AB  - For years researchers have exerted every effort to improve the influential roles
      of microRNA (miRNA) in regulating genes that direct mammalian cell development
      and function. In spite of numerous advancements, many facets of miRNA generation
      remain unresolved due to the perplexing regulatory networks. The biogenesis of
      miRNA, eminently endures as a mystery as no universal pathway defines or
      explicates the variegation in the rise of miRNAs. Early evidence in biogenesis
      ignited specific steps of being omitted or replaced that eventuate in the
      individual miRNAs of different mechanisms. Understanding the basic foundation
      concerning how miRNAs are generated and function will help with diagnostic tools
      and therapeutic strategies. This review encompasses the canonical and the non
      canonical pathways involved in miRNA biogenesis, while elucidating how miRNAs
      regulate genes at the nuclear level and also the mechanism that lies behind
      circulating miRNAs. 

PMID- 24588708
TI  - Synthetic biology: old wine in new bottles with an emerging language that ranges
      from the sublime to the ridiculous?

PMID- 24588709
TI  - Interpreting species-specific variation in tree-ring oxygen isotope ratios among
      three temperate forest trees.
AB  - Although considerable variation has been documented in tree-ring cellulose oxygen
      isotope ratios (delta(18)O(cell)) among co-occurring species, the underlying
      causes are unknown. Here, we used a combination of field measurements and
      modelling to investigate the mechanisms behind variations in late-wood delta(18)
      O(cell) (delta(18)O(lc)) among three co-occurring species (chestnut oak, black
      oak and pitch pine) in a temperate forest. For two growing seasons, we quantified
      among-species variation in delta(18)O(lc), as well as several variables that
      could potentially cause the delta(18)O(lc) variation. Data analysis based on the
      delta(18) O(cell) model rules out leaf water enrichment (Delta(18)O(lw)) and tree
      ring formation period (Deltat), but highlights source water delta(18) O
      (delta(18) O(sw)) as an important driver for the measured difference in
      delta(18)O(lc) between black and chestnut oak. However, the enriched
      delta(18)O(lc) in pitch pine relative to the oaks could not be sufficiently
      explained by consideration of the above three variables only, but rather, we show
      that differences in the proportion of oxygen exchange during cellulose synthesis
      (p(ex)) is most likely a key mechanism. Our demonstration of the relevance of
      some species-specific features (or lack thereof) to delta(18)O(cell) has
      important implications for isotope based ecophysiological/paleoclimate studies.

PMID- 24588710
TI  - Seasonal colour and antipredator behaviour in Etheostoma (Percidae).
AB  - This study examined how colour varies across season and sex in the fantail darter
      Etheostoma flabellare and the banded darter Etheostoma zonale. Etheostoma
      flabellare has male-only parental care and exhibited slight sexual dimorphism in
      overall colour, with no discernible effect of season on colour; whereas E. zonale
      does not have parental care and exhibited substantial sexual dimorphism in
      colour, but only in the breeding season. Additionally, antipredator behaviour of
      E. zonale was compared between males that were fully coloured during the breeding
      season and males that were partially coloured at that time, but the effects of
      colour and season were not consistent across males. 

PMID- 24588711
TI  - Classification and proposed nomenclature for inherited defects of thyroid hormone
      action, cell transport, and metabolism.

PMID- 24588712
TI  - The bifacial role of helminths in cancer: involvement of immune and non-immune
      mechanisms.
AB  - Infectious agents have been associated with cancer due to activation of pro
      carcinogenic inflammatory processes within their host. Several reports, however,
      indicate that specific pathogens may be able to elicit anti-tumor immune
      responses that can lead to protection from tumorigenesis or cancer regression.
      Amongst these "beneficial" pathogens are some helminthic parasites that have
      already been connected with prevention of autoimmune diseases and allergies,
      immune conditions increasingly associated with cancer. Even though helminths have
      co-existed with humans and their ancestors for millions of years, investigations
      of their impact on human (patho)physiology are relatively new and the functions
      of components that can explain the helminth bi-directional influence on
      carcinogenesis are not well understood. This review aims to discuss evidence for
      the helminth-induced immune, genetic, epigenetic, proteomic, hormonal and
      metabolic changes that may ultimately mediate the potential pro- or anti
      carcinogenic role of helminths. This overview may serve future investigations in
      clarifying the tumorigenic role of the most common helminthic parasites. It may
      also inspire the development of anti-cancer regimens and vaccines, in parallel to
      ongoing efforts of using helminth-based components for the prevention and/or
      treatment of autoimmune diseases and allergies.

PMID- 24588713
TI  - Terminal aryl alkenes and alkynes as arylcarboxy surrogates toward o
      benzoxylation of 2-phenylpyridine catalyzed by copper.
AB  - A variety of styrenes and phenylacetylenes serve as excellent arylcarboxy sources
      in bringing about substrate directed o-benzoxylation of 2-phenylpyridine
      derivatives catalyzed by Cu(II) in the presence of TBHP. This reaction proceeds
      via formation of phenylglyoxal followed by decarbonylation to benzoyl
      radical/benzaldehyde which acts as the arylcarboxy source. 

PMID- 24588714
TI  - Widespread occurrence of benzophenone-type UV light filters in personal care
      products from China and the United States: an assessment of human exposure.
AB  - Benzophenone-3 (BP-3) is a sunscreen agent used in a variety of personal care
      products (PCPs) for the protection of human skin and hair from damage by
      ultraviolet (UV) radiation. Concerns have been raised over exposure of humans to
      BP-3, owing to the estrogenic potential of this compound. Nevertheless, the
      levels and profiles of BP-3 in PCPs and sources of exposure of humans to this
      estrogenic compound are not well-known. In this study, concentrations of BP-3
      were determined in seven categories of 231 PCPs collected from several cities in
      China (n = 117) and the United States (U.S.) (n = 114), using high-performance
      liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). BP-3 was found in
      the majority (81%) of the samples analyzed, at concentrations as high as 0.148%.
      The highest BP-3 concentrations (geometric mean [GM]: 548; median: 530 ng/g) were
      found in skin lotions (including sunscreen lotions), followed by makeup products
      (284; 221 ng/g). PCPs collected from the U.S. contained higher concentrations of
      BP-3 than those collected from China. On the basis of the concentrations measured
      and daily usage rates of PCPs, we estimated the daily intake of BP-3 through
      dermal absorption from the use of PCPs. The GM and 95th percentile exposure doses
      to BP-3 were 0.978 and 25.5 MUg/day, respectively, for adult women in China,
      which were 2 orders of magnitude lower than those found for adult women in the
      U.S. (24.4 and 5160 MUg/day). Skin lotions and face creams contributed to the
      preponderance of daily BP-3 exposures (>80%). 

PMID- 24588715
TI  - One-stage surgical correction in pentalogy of Cantrell with left ventricular
      diverticulum.
AB  - The pentalogy of Cantrell is a rare and fatal malformation. A left ventricular
      diverticulum is a common finding of this pentalogy. The present report summarizes
      our experience with three patients who suffered from pentalogy of Cantrell. All
      three cases had a left ventricular diverticulum. The intracardiac malformations
      and the left ventricular diverticulum were corrected simultaneously. All patients
      recovered uneventfully. One-stage surgical correction could improve short-term
      outcomes in selected patients with pentalogy of Cantrell.

PMID- 24588716
TI  - Nanoporous cobalt(II) MOF exhibiting four magnetic ground states and changes in
      gas sorption upon post-synthetic modification.
AB  - We present the syntheses, structural characterization, gas sorption, I2 uptake,
      and magnetic properties of a double-walled porous metal-organic framework,
      [Co(II)3(lac)2(pybz)2].3DMF (1.3DMF, purple, where pybz = 4-pyridyl benzoate, lac
      = d- and l-lactate) and of its post-synthetic modified (PSM) congeners,
      [Co(II)3(lac)2(pybz)2].xGuest (xGuest = 6MeOH, purple; 4.5EtOH, purple; 3PrOH,
      purple; 2C6H6, purple; 2.7I2, black), [Co(II)3(lac)2(pybz)2] (1, purple),
      [Co(II)3(pybz)2(lac)2(H2O)2].7H2O (1a.7H2O, green), and
      [Co(III)Co(II)2(pybz)2(lac)2(H2O)2]I.2H2O.1.5DMSO (1b.I(-).2H2O.1.5DMSO, yellow,
      DMSO = dimethyl sulfoxide). Crystallography shows that the framework is not
      altered by the replacement of DMF by different solvents or by the removal of the
      solvent molecules during the single-crystal to single-crystal (SC-SC)
      transformations, while upon exchange with H2O or partial oxidation by molecular
      iodine, the crystallinity is affected. 1 absorbs N2, H2, CH4, CH3OH, C2H5OH,
      PrOH, C6H6, and I2, but once it is in contact with H2O the absorption efficiency
      is drastically reduced. Upon PSM, the magnetism is transformed from a canted
      antiferromagnet (1.3DMF and 1.xGuest) to single-chain magnet (1), to a
      ferrimagnet (1a.7H2O), and to a ferromagnet (1b.I(-).2H2O.1.5DMSO). Raman
      spectroscopy suggests the color change (purple to green 1a.7H2O or yellow 1b.I(
      ).2H2O.1.5DMSO) is associated with a change of geometry from a strained
      octahedron due to the very acute chelating angle (~60 degrees ) of the lactate of
      a cobalt center to a regular octahedron with a monodentate carboxylate and one
      H2O. The magnetic transformation is explained by the different interchain
      exchanges (J'), antiferromagnetic for 1.3DMF and 1.xSolvent (J' < 0), SCM for 1
      (J' verge to 0), and ferromagnetic for 1a.7H2O (J' > 0), between homometal
      topological ferrimagnetic chains (two octahedral and one tetrahedral Co(II) ions)
      connected by the double walls of pybz at 13.3 A (shortest Co...Co). For 1b.I(
      ).2H2O.1.5DMSO the moment of the tetrahedral site is turned off, thus stabilizing
      a ferromagnetic state (J' > 0). The present stabilization of four magnetic ground
      states is unique in the field of metal-organic frameworks as well as the
      electrical conductivity of 1.2.7I2. 

PMID- 24588717
TI  - Signalling protein complexes isolated from primary human skin-resident T cells
      can be analysed by Multiplex IP-FCM.
AB  - Studying signal transduction in skin-resident T cells (sr-T cells) can be limited
      by the small size of clinical biopsies. Here, we isolated sr-T cells from
      clinical samples and analysed signalling protein complexes by multiplex
      immunoprecipitation detected by flow cytometry (mIP-FCM). In samples from two
      independent donors, antigenic stimulation induced signalling proteins to join
      shared complexes that were observed in seven pairwise combinations among five
      proteins. This demonstrates that sr-T cells isolated from small clinical samples
      provide sufficient material for mIP-FCM-based analysis of signalling-induced
      protein complexes. We propose that this strategy may be useful for gaining
      improved mechanistic insight of sr-T cell signal transduction associated with
      dermatological disease. 

PMID- 24588718
TI  - New La(III) complex immobilized on 3-aminopropyl-functionalized silica as an
      efficient and reusable catalyst for hydrolysis of phosphate ester bonds.
AB  - Described herein is the synthesis, structure, and monoesterase and diesterase
      activities of a new mononuclear [La(III)(L(1))(NO3)2] (1) complex (H2L(1) = 2
      bis[{(2-pyridylmethyl)-aminomethyl}-6-[N-(2-pyridylmethyl) aminomethyl)])-4
      methyl-6-formylphenol) in the hydrolysis of 2,4-bis(dinitrophenyl)phosphate (2,4
      BDNPP). When covalently linked to 3-aminopropyl-functionalized silica, 1
      undergoes disproportionation to form a dinuclear species (APS-1), whose catalytic
      efficiency is increased when compared to the homogeneous reaction due to second
      coordination sphere effects which increase the substrate to complex association
      constant. The anchored catalyst APS-1 can be recovered and reused for subsequent
      hydrolysis reactions (five times) with only a slight loss in activity. In the
      presence of DNA, we suggest that 1 is also converted into the dinuclear active
      species as observed with APS-1, and both were shown to be efficient in DNA
      cleavage. 

PMID- 24588719
TI  - A dietary restriction influences the progression but not the initiation of MSG
      Induced nonalcoholic steatohepatitis.
AB  - The metabolic syndrome is a major worldwide health care issue and a dominant risk
      factor for cardiovascular disease. The liver manifestations of this syndrome
      include nonalcoholic fatty liver disease (NAFLD) and its progressive variant
      nonalcoholic steatohepatitis (NASH). Although significant research has been
      performed, the basic pathogenesis of NAFLD/NASH remains controversial and
      effective treatments are still unavailable. We have previously reported on a
      murine model of NASH induced by the neonatal injection of monosodium glutamate
      (MSG), which includes the clinical manifestations of central obesity, diabetes,
      hyperlipidemia, and ultimately liver inflammation, fibrosis, and cancer. Although
      MSG is considered a safe food additive, its administration to pregnant rats
      increases the voracity and growth hormone levels in the offspring. To further
      understand the biology of this model, we have investigated the influence of the
      calorie intake on these clinical manifestations by feeding animals a restrictive
      diet. MSG-treated animals fed a restrictive diet continue to manifest obesity and
      early stage NASH but have improvements in serum lipid profiles. At 12 months of
      age, mice had manifestations of obesity, whether animals were fed a restricted or
      control diet, but animals fed a restrictive diet had a reduction in the
      progression of NASH. In conclusion, MSG appears to be a critical factor in the
      initiation of obesity, whereas calorie intake may modulate the progression of
      disease.

PMID- 24588720
TI  - Identification and potential application of human corneal endothelial progenitor
      cells.
AB  - The corneal endothelium is believed to be developmentally originated from the
      periocular mesenchyme via the neural crest. Human corneal endothelial progenitor
      cells (HCEPs) have been investigated because of their potential availability for
      the tissue regenerative medicine. However, the existence and the properties of
      HCEPs have not been elucidated yet. We first established a novel serum-free
      culture system for HCEPs. The HCEPs highly expressed p75 neurotrophin receptor,
      SOX9, and FOXC2, and partially retained the properties of neural crest and
      periocular mesenchyme. Further, we demonstrated that HCEPs had a high
      proliferative potency, and the differentiated HCEP sheets had corneal endothelial
      function by using the Ussing chamber system and transplantation to the rabbit
      cornea. These findings suggest that the HCEPs can be selectively expanded from
      the corneal endothelium using a specific culture system and will provide cell
      sheets for corneal regenerative medicine. 

PMID- 24588722
TI  - What is your diagnosis? An intraocular mass in a dog.

PMID- 24588721
TI  - Design of porous silica supported tantalum oxide hollow spheres showing enhanced
      photocatalytic activity.
AB  - Silica-supported tantalum oxide (ST) hollow spheres were designed for
      photocatalytic applications in the UV range of 4.1 to 4.8 eV. These
      nanostructures with a variable diameter of 100-250 nm and shell thickness of 24
      58 nm were obtained by the hydrothermal treatment of tantalum isopropoxide and
      tetraethylorthosilicate at 120  degrees C for 48 h in the presence of cetyl
      trimethyl ammonium bromide, which was used as a capping agent. The maximum
      observed surface area was found to be 610 m(2)/g and pore size distribution of ST
      hollow spheres varied from 13.4 to 19.0 nm. Lewis acidity of silica and the
      contact area between SiO2 and Ta2O5 plays a crucial role in controlling the
      photocatalytic properties of the ST hollow spheres. We observe a remarkable 6*
      enhancement in the photoactivity of silica-supported tantalum oxide hollow
      spheres compared to pure Ta2O5. 

PMID- 24588725
TI  - High intrinsic mechanical flexibility of mouse prion nanofibrils revealed by
      measurements of axial and radial Young's moduli.
AB  - Self-templated protein aggregation and intracerebral deposition of aggregates,
      sometimes in the form of amyloid fibrils, is a hallmark of mammalian prion
      diseases. What distinguishes amyloid fibrils formed by prions from those formed
      by other proteins is not clear. On the basis of previous studies on yeast prions
      that correlated high intrinsic fragmentation rates of fibrils with prion
      propagation efficiency, it has been hypothesized that the nanomechanical
      properties of prion amyloid such as strength and elastic modulus may be the
      distinguishing feature. Here, we reveal that fibrils formed by mammalian prions
      are relatively soft and clearly in a different class of rigidities when compared
      to nanofibrils formed by nonprions. We found that amyloid fibrils made of both
      wild-type and mutant mouse recombinant PrP(23-231) have remarkably low axial
      elastic moduli of 0.1-1.4 GPa. We demonstrate that even the proteinase K
      resistant core of these fibrils has similarly low intrinsic rigidities. Using a
      new mode of atomic force microscopy called AM-FM mode, we estimated the radial
      modulus of PrP fibrils at ~0.6 GPa, consistent with the axial moduli derived by
      using an ensemble method. Our results have far-reaching implications for the
      understanding of protein-based infectivity and the design of amyloid
      biomaterials. 

PMID- 24588726
TI  - Parametric bootstrap methods for testing multiplicative terms in GGE and AMMI
      models.
AB  - The genotype main effects and genotype-by-environment interaction effects (GGE)
      model and the additive main effects and multiplicative interaction (AMMI) model
      are two common models for analysis of genotype-by-environment data. These models
      are frequently used by agronomists, plant breeders, geneticists and statisticians
      for analysis of multi-environment trials. In such trials, a set of genotypes, for
      example, crop cultivars, are compared across a range of environments, for
      example, locations. The GGE and AMMI models use singular value decomposition to
      partition genotype-by-environment interaction into an ordered sum of
      multiplicative terms. This article deals with the problem of testing the
      significance of these multiplicative terms in order to decide how many terms to
      retain in the final model. We propose parametric bootstrap methods for this
      problem. Models with fixed main effects, fixed multiplicative terms and random
      normally distributed errors are considered. Two methods are derived: a full and a
      simple parametric bootstrap method. These are compared with the alternatives of
      using approximate F-tests and cross-validation. In a simulation study based on
      four multi-environment trials, both bootstrap methods performed well with regard
      to Type I error rate and power. The simple parametric bootstrap method is
      particularly easy to use, since it only involves repeated sampling of standard
      normally distributed values. This method is recommended for selecting the number
      of multiplicative terms in GGE and AMMI models. The proposed methods can also be
      used for testing components in principal component analysis.

PMID- 24588727
TI  - Th2-type cytokine-induced mucus metaplasia decreases susceptibility of human
      bronchial epithelium to rhinovirus infection.
AB  - Human rhinoviruses (RVs) are a major cause of exacerbations in asthma and other
      chronic airway diseases. A characteristic feature of asthmatic epithelium is
      goblet cell metaplasia and mucus hypersecretion. Bronchial epithelium is also an
      important source of lipid mediators, including pro- and antiinflammatory
      eicosanoids. By using air-liquid interface cultures of airway epithelium from
      patients with asthma and nonasthmatic control subjects, we compared RV16
      replication-induced changes in mRNA expression of asthma candidate genes and
      eicosanoid production in the epithelium with or without IL-13-induced mucus
      metaplasia. Mucus metaplastic epithelium was characterized by a 20-fold less
      effective replication of RV16 and blunted changes in gene expression; this effect
      was seen to the same extent in patients with asthma and control subjects. We
      identified ciliary cells as the main target for RV16 by immunofluorescence
      imaging and demonstrated that the numbers of ciliary cells decreased in RV16
      infected epithelium. RV16 infection of mucociliary epithelium resulted in
      overexpression of genes associated with bronchial remodeling (e.g., MUC5AC, FGF2,
      and HBEGF), induction of cyclooxygenase-2, and increased secretion of
      prostaglandins. These responses were similar in both studied groups. These data
      indicate that structural changes associated with mucus metaplasia renders airway
      epithelium less susceptible to RV infection. Thus, exacerbations of the lung
      disease caused by RV may result from severe impairment in mucociliary clearance
      or activation of immune defense rather than from preferential infection of mucus
      metaplastic epithelium. Repeated rhinoviral infections of compromised epithelium
      may contribute to the remodeling of the airways. 

PMID- 24588728
TI  - I2-promoted selective oxidative cross-coupling/annulation of 2-naphthols with
      methyl ketones: a strategy to build naphtho[2,1-b]furan-1(2H)-ones with a
      quaternary center.
AB  - A highly efficient and selective molecular iodine-promoted oxidative cross
      coupling/annulation between 2-naphthols and methyl ketones has been realized. The
      reaction successfully constructed a new quaternary carbon center within 3(2H)
      furanones. Our synthetic strategy provided an in situ iodination-based oxidative
      coupling pathway. Based on the experimental results, a self-sequenced
      iodination/Kornblum oxidation/Friedel-Crafts/oxidation/cyclization mechanism was
      proposed. 

PMID- 24588731
TI  - Direct and indirect chemical defences against insects in a multitrophic
      framework.
AB  - Plant secondary metabolites play an important role in mediating interactions with
      insect herbivores and their natural enemies. Metabolites stored in plant tissues
      are usually investigated in relation to herbivore behaviour and performance
      (direct defence), whereas volatile metabolites are often studied in relation to
      natural enemy attraction (indirect defence). However, so-called direct and
      indirect defences may also affect the behaviour and performance of the
      herbivore's natural enemies and the natural enemy's prey or hosts, respectively.
      This suggests that the distinction between these defence strategies may not be as
      black and white as is often portrayed in the literature. The ecological costs
      associated with direct and indirect chemical defence are often poorly understood.
      Chemical defence traits are often studied in two-species interactions in highly
      simplified experiments. However, in nature, plants and insects are often engaged
      in mutualistic interactions with microbes that may also affect plant secondary
      chemistry. Moreover, plants are challenged by threats above- and belowground and
      herbivory may have consequences for plant-insect multitrophic interactions in the
      alternative compartment mediated by changes in plant secondary chemistry. These
      additional associations further increase the complexity of interaction networks.
      Consequently, the effect of a putative defence trait may be under- or
      overestimated when other interactions are not considered. 

PMID- 24588730
TI  - Lethal and sublethal effects of imidacloprid, after chronic exposure, on the
      insect model Drosophila melanogaster.
AB  - Neonicotinoids are subjected to vigilance because of environmental contaminations
      and deleterious effects on bees. Imidacloprid (IMI) is one of the most
      representative insecticides of this family. At chronic exposure, concentration
      effect relationships are non linear. An insect model should allow a better
      description of this toxicity. We compared the lethal concentration 50% (LC50) of
      IMI for a Drosophila-field strain, after acute and chronic exposure. Relative to
      the acute LC50, the chronic LC50 was lowered by a factor of 29 for males (1.3
      mM/45 MUM), 52 for larvae (157 MUM/3 MUM) and more than 172 for females (>3.1
      mM/18 MUM). Chronic exposure also revealed significant lethal and sublethal
      effects, at concentrations 3-5 orders of magnitude lower than the chronic LC50.
      Mean mortalities reached 28% (at 3.91 nM) and 27% (at 39.1 nM) for females and
      males, respectively. Fecundity decreased of 16% at 1.96 nM. Mating increased of
      30% at 0.391 nM. The LOEC (lowest observed effect concentration: 0.391 nM) was 46
      000 times lower than the chronic LC50 for males; it was 115 000 times lower than
      the chronic LC50 for females. This study illuminates effects that neonicotinoids
      can induce at very low concentrations. This is of particular interest for
      nontarget insects and for insect dependent species. 

PMID- 24588732
TI  - Thermal stratification influences maturation and timing of spawning in a local
      Clupea harengus population.
AB  - Maturation and timing of spawning in relation to temperature were studied in a
      local Atlantic herring Clupea harengus population inhabiting a small semi
      enclosed ecosystem (7 km(2)) separated from the larger outer fjord system by
      narrow sills on the west coast of Norway. Ambient temperatures varied annually up
      to 4 degrees  C during both the pre-spawning and spawning periods from February
      to April, but without affecting the spawning time. Instead, the timing of
      spawning was found to be related to thermal stratification in response to spring
      warming, which occurred about the same time every year regardless of initial
      temperatures.

PMID- 24588729
TI  - The current state of drug discovery and a potential role for NMR metabolomics.
AB  - The pharmaceutical industry has significantly contributed to improving human
      health. Drugs have been attributed to both increasing life expectancy and
      decreasing health care costs. Unfortunately, there has been a recent decline in
      the creativity and productivity of the pharmaceutical industry. This is a complex
      issue with many contributing factors resulting from the numerous mergers,
      increase in out-sourcing, and the heavy dependency on high-throughput screening
      (HTS). While a simple solution to such a complex problem is unrealistic and
      highly unlikely, the inclusion of metabolomics as a routine component of the drug
      discovery process may provide some solutions to these problems. Specifically, as
      the binding affinity of a chemical lead is evolved during the iterative structure
      based drug design process, metabolomics can provide feedback on the selectivity
      and the in vivo mechanism of action. Similarly, metabolomics can be used to
      evaluate and validate HTS leads. In effect, metabolomics can be used to eliminate
      compounds with potential efficacy and side effect problems while prioritizing
      well-behaved leads with druglike characteristics. 

PMID- 24588733
TI  - Effects of subcutaneously injected Ca Cu EDTA on concentrations of Cu in liver,
      milk production and reproductive performance in New Zealand dairy cows.
AB  - AIMS: To determine the effect of dose and frequency of injection of Cu as Ca Cu
      EDTA on concentrations of Cu in liver, and the effect of a single 200 mg
      treatment on milk production and reproductive performance in New Zealand dairy
      cows. METHODS: Four groups of dairy cows (n=18 per group) on three farms were
      injected with 100 or 200 mg Cu S/C once, or three times at 6-weekly intervals,
      commencing 6-8 weeks into lactation. Concentrations of Cu in liver were
      determined to 119 days after treatment. Cows at peak lactation on one farm were
      treated with 200 mg of Cu S/C, or received no treatment (n=92 per group). Milk
      production was determined 11 days before and 24 hours following treatment. In
      seven dairy herds from throughout New Zealand cows were injected S/C with 200 mg
      Cu 10 days prior to mating start date (MSD) or received no treatment. Oestrus
      detection and artificial inseminations were carried out for >= 2 - 4 days from
      MSD. Pregnancy diagnosis was performed at 12 weeks following MSD. The percentage
      of cows inseminated in the 21 days after MSD (21-day submission rate; n=2,022)
      and cows pregnant after 21 or 28 days (21- and 28-day pregnancy rates; n=2520)
      was determined. RESULTS: Injecting with 200 mg Cu once or 6-weekly increased
      concentrations of Cu in liver compared with 100 mg (p<0.05). Injection of 200 mg
      Cu decreased total milk yield (p=0.006) and protein production (p<0.001) in the
      24-36 hours after treatment. Compared with Control cows, 200 mg Cu 10 days before
      MSD reduced 21-day submission (78 vs. 75%; p=0.04) and 21-day pregnancy rates (47
      vs. 43%; p=0.03). For 28-day pregnancy rates there was a farm by treatment
      interaction (p=0.02), with a negative effect observed on some, but not other,
      farms. CONCLUSIONS: Injection of 200 mg Cu raised concentrations of Cu in liver
      for >42 days. A negative impact on milk yield and composition occurred
      immediately following injection. Injection 10 days prior to mating had a negative
      effect on submission and pregnancy rates. Further study is required to determine
      a safe treatment to mating interval and the mechanism by which adverse impacts
      occur. CLINICAL REVELENCE: Although 200 mg of Cu as Ca Cu EDTA is an effective
      supplement and generally well tolerated, determining the necessity for, and
      giving specific thought to the timing of, parenteral Cu supplementation is
      imperative to avoid negative impacts on herd production and reproductive
      performance.

PMID- 24588734
TI  - Disease-specific survival for patients with multiple myeloma: significant
      improvements over time in all age groups.
AB  - This study analyzed the survival of patients with multiple myeloma. Surveillance,
      Epidemiology, and End Results (SEER) and Centers for Disease Control and
      Prevention (CDC) databases were queried to calculate myeloma cause-specific
      survival curves by the Kaplan and Meier product-limit method. The Cox
      proportional hazards model was used to assess univariate and multivariate
      predictors of myeloma cause-specific survival. The outcome of interest was death
      due to myeloma. Results from a Cox proportional hazards model restricted to age
      and time period at diagnosis demonstrated that the magnitude of improvement in
      survival by time period varied by age at diagnosis. Among patients under 60 years
      at diagnosis, hazard ratios for myeloma cause-specific death decreased by more
      50% from the first interval of observation to the last. Hazard ratios decreased
      during the study period by 39% among patients 60-69 years of age and by 27% among
      patients who were 70 years of age and older. Survival is improving in patients
      with myeloma of all ages.

PMID- 24588735
TI  - The impact of race, ethnicity, age and sex on clinical outcome in chronic
      lymphocytic leukemia: a comprehensive Surveillance, Epidemiology, and End Results
      analysis in the modern era.
AB  - To analyze racial, ethnic, sex and age disparities in chronic lymphocytic
      leukemia (CLL), we examined population-based overall survival (OS) data from
      Surveillance, Epidemiology, and End Results (SEER)-13 (1992-2009) across various
      races/ethnicities over two consecutive 9-year periods: era 1 (1992-2000) and era
      2 (2001-2009). We analyzed 28 590 patients (whites: 24 438, blacks: 1954,
      Hispanics: 1389 and Asians/Pacific Islanders [A/PI]: 809). A higher proportion of
      whites were aged > 80 years (22% vs. 17% [Hispanics], 16% [blacks], 16% [A/PI]; p
      < 0.001). Higher socioeconomic status (SES) was also identified for A/PI and
      whites compared with blacks and Hispanics (p < 0.001). OS for all patients
      improved at 5 years (66% vs. 60%, p < 0.0001) and was significant in all
      races/ethnicities except A/PI. Patients of higher SES had better outcomes than
      others independent of era, but both SES classes experienced relative improvement
      in their OS across eras. The OS of patients with CLL has improved in the modern
      era but racial/ethnic, gender and SES differences persist, warranting further
      investigation.

PMID- 24588736
TI  - Targeting drug resistance to close the gap in diffuse large B-cell lymphoma.

PMID- 24588737
TI  - Interim and end-treatment positron emission tomography scan in aggressive B-cell
      lymphoma: we still lack an interpretation key.

PMID- 24588738
TI  - An isothiourea-catalyzed asymmetric [2,3]-rearrangement of allylic ammonium
      ylides.
AB  - Benzotetramisole promotes the catalytic asymmetric [2,3]-rearrangement of allylic
      quaternary ammonium salts (either isolated or prepared in situ from p-nitrophenyl
      bromoacetate and the corresponding allylic amine), generating syn-alpha-amino
      acid derivatives with excellent diastereo- and enantioselectivity (up to >95:5
      dr; up to >99% ee). 

PMID- 24588739
TI  - Molecular abnormalities of the B cell in systemic lupus erythematosus are
      candidates for functional inhibition treatments.
AB  - INTRODUCTION: The B cell is a key player in the pathogenesis of systemic lupus
      erythematosus (SLE). Loss of B cell tolerance resulting in autoantibody
      production and immune complex formation and deposition are central features of
      the disease. B cell overactivity is a hallmark of SLE and molecular abnormalities
      in B cell signaling cascade have been described. AREAS COVERED: In this review,
      we will focus on the aberrant phenotype of B cell signaling in patients with
      lupus. We will also discuss data stemming from the use of small molecules that
      have recently been recognized to target important steps of the B cell signal
      transduction pathways with therapeutic implications for SLE. EXPERT OPINION:
      Attempts to target the B cell in SLE have been made through depletion, blocking
      of survival factors and co-receptor inhibition. However, the still unmet need for
      effective therapy of refractory disease makes the necessity for new drugs
      impelling.

PMID- 24588741
TI  - Wetting-induced coalescence of nanoliter drops as microreactors in microfluidics.
AB  - Controllable one-to-one coalescence of surfactant-stabilized nanoliter water
      drops is successfully achieved from wetting-induced drop engulfing in
      microfluidics by surrounding one of the drops with a thin layer of immiscible
      wetting fluid. This wetting layer can spread over the other drop to drain away
      the liquid film between the two drops, thereby inducing coalescence. This
      innovative approach is totally spontaneous and highly potential in a myriad of
      fields, such as quantitative analysis, microreaction, and high-throughput
      injection. To demonstrate this potential, we successfully perform the drop
      coalescence-triggered microreaction in microchannels for pH indicator and
      syntheses of functional materials including micro- and nanoparticles. 

PMID- 24588740
TI  - Formulation and evaluation of gastroretentive floating drug delivery system of
      dipyridamole.
AB  - A multiple-unit floating alginate bead drug delivery system with prolonged
      stomach retention time was developed in this study. The floating alginate beads
      were prepared by ionic cross-linking method, using CaCO3 as the gas-forming
      agent. Over 92% of the beads remained floating after 9 h. In order to prepare
      sustained-release dosage forms of dipyridamole, the solid dispersion technique
      was applied using a blend of Eudragit L100 and Eudragit RLPO. Afterwards, the
      solid dispersions of dipyridamole were incorporated into the floating alginate
      beads. The drug release was modified by changing the ratio of Eudragit RLPO and
      Eudragit L100 in the solid dispersions. The in vivo results showed that the
      relative bioavailability of alginate beads was enhanced by approximately 2.52
      fold compared with that of the commercial tablet. Therefore, our study
      illustrated the potential use of floating alginate beads combined with the solid
      dispersion technique for the delivery of acid-soluble compounds, such as
      dipyridamole. 

PMID- 24588742
TI  - MoS2 field-effect transistor for next-generation label-free biosensors.
AB  - Biosensors based on field-effect transistors (FETs) have attracted much
      attention, as they offer rapid, inexpensive, and label-free detection. While the
      low sensitivity of FET biosensors based on bulk 3D structures has been overcome
      by using 1D structures (nanotubes/nanowires), the latter face severe fabrication
      challenges, impairing their practical applications. In this paper, we introduce
      and demonstrate FET biosensors based on molybdenum disulfide (MoS2), which
      provides extremely high sensitivity and at the same time offers easy
      patternability and device fabrication, due to its 2D atomically layered
      structure. A MoS2-based pH sensor achieving sensitivity as high as 713 for a pH
      change by 1 unit along with efficient operation over a wide pH range (3-9) is
      demonstrated. Ultrasensitive and specific protein sensing is also achieved with a
      sensitivity of 196 even at 100 femtomolar concentration. While graphene is also a
      2D material, we show here that it cannot compete with a MoS2-based FET biosensor,
      which surpasses the sensitivity of that based on graphene by more than 74-fold.
      Moreover, we establish through theoretical analysis that MoS2 is greatly
      advantageous for biosensor device scaling without compromising its sensitivity,
      which is beneficial for single molecular detection. Furthermore, MoS2, with its
      highly flexible and transparent nature, can offer new opportunities in advanced
      diagnostics and medical prostheses. This unique fusion of desirable properties
      makes MoS2 a highly potential candidate for next-generation low-cost biosensors. 

PMID- 24588743
TI  - What is your diagnosis? Dermal mass in a dog.

PMID- 24588744
TI  - The pqqC gene is essential for antifungal activity of Pseudomonas kilonensis JX22
      against Fusarium oxysporum f. sp. lycopersici.
AB  - Strain JX22, exhibiting a broad range of antimicrobial activities to fungal
      pathogens, was isolated and classified as representing Pseudomonas kilonensis. In
      this study, the mutant JX22MT1 was obtained by the EZ-Tn5 transposon mutation and
      showed no antifungal activity against Fusarium oxysporum f. sp. lycopersici as
      compared with wild-type strain JX22. The pqqC gene was disrupted in the mutant.
      Antifungal activity at the wild-type level was restored from the mutant JX22MT1
      with the introduction of the functional pqqC gene, which encodes pyrroloquinoline
      quinone synthesis protein C. The results suggest that pqqC is essential for
      antifungal activity of P. kilonensis JX22 against F. oxysporum f. sp.
      lycopersici.

PMID- 24588745
TI  - How, and from which cell sources, do nevi really develop?
AB  - Melanocytic neoplasms are a diverse group of benign and malignant tumors with
      variable clinical features. While some models still promote the epidermal
      melanocyte as the origin of melanocytic neoplasms, clinical findings are
      inconsistent with this theory for the majority of tumors. Despite advances in
      naevus and melanoma biology, the location and differentiation status of the cell
      of origin remains undefined. Germ line genetics, biological state and cellular
      location of the mutated cell, as well as local environmental factors all likely
      play a role in the development of melanocytic neoplasms. Herein, we will review
      potential models for melanocytic neoplasia and discuss research challenges and
      opportunities. 

PMID- 24588747
TI  - Copper-catalyzed intermolecular aminoazidation of alkenes.
AB  - Copper-catalyzed intermolecular aminoazidation of alkenes is described. This
      novel methodology provides an efficient approach to vicinal amino azides which
      can easily be transformed into other valuable amine derivatives. The commercially
      available N-fluorobenzenesulfonimide (NFSI) is used as a nitrogen-radical
      precursor and TMSN3 as the N3 source. Yields are moderate to excellent, and for
      internal alkenes aminoazidation occurs with excellent diastereoselectivity. 

PMID- 24588746
TI  - In vitro versus in situ evaluation of the effect of phytase supplementation on
      calcium and phosphorus solubility in soya bean and rapeseed meal broiler diets.
AB  - 1. In vitro assays provide a rapid and economical tool to evaluate dietary
      effects, but have limitations. In this study, the effect of phytase
      supplementation on solubility, and presumed availability, of calcium (Ca) and
      phosphorus (P) in soya bean meal (SBM) and rapeseed meal (RSM) based diets were
      evaluated both in situ and by a two-step in vitro digestion assay that simulated
      the gastric and small intestine (SI) phases of digestion. 2. Comparison of the in
      vitro findings to in situ findings was used to evaluate the in vitro assay. Ross
      308 broilers (n = 192) were fed on one of 6 SBM or RSM diets supplemented with 0,
      500 or 5000 FTU/kg phytase from 0 to 28 d post hatch. The 6 diets and raw SBM and
      RSM were exposed to a two-step in vitro assay. Ca and P solubility and pH in the
      gizzard and jejunal digesta and in the gastric and SI phase of in vitro digestion
      were measured. 3. Both in vitro and in situ analyses detected that Ca solubility
      was lowest when diets were supplemented with 500 FTU/kg phytase, compared to the
      control diets and diets supplemented with 5000 FTU/kg phytase. Phosphorus
      solubility increased with increasing phytase level. Both methods also identified
      that mineral solubility plateaus in the gastric phase. 4. Overall relationship of
      the two methods was strong for both determination of gastric phase Ca and P
      solubility (r = 0.96 and 0.92, respectively) and also SI phase Ca and P
      solubility (r = 0.71 and 0.82, respectively). However, mineral solubility and pH
      were higher when measured in vitro than in situ, and the in situ assay identified
      an interaction among the effects of phase, protein source and phytase inclusion
      level on Ca solubility that the in vitro assay did not detect. 5. This two-step
      in vitro assay successfully predicted phytase efficacy, but to determine detailed
      response effects in the animal, in situ data is still required.

PMID- 24588749
TI  - Microcapsules fabricated from liquid marbles stabilized with latex particles.
AB  - Millimeter- and centimeter-sized "liquid marbles" were readily prepared by
      rolling water droplets on a powder bed of dried submicrometer-sized polystyrene
      latex particles carrying poly[2-(diethylamino)ethyl methacrylate] hairs (PDEA
      PS). Scanning electron microscopy studies indicated that flocs of the PDEA-PS
      particles were adsorbed at the surface of these water droplets, leading to stable
      spherical liquid marbles. The liquid marbles were deformed as a result of water
      evaporation to adopt a deflated spherical geometry, and the rate of water
      evaporation decreased with increasing atmospheric relative humidity. Conversely,
      liquid marbles formed using saturated aqueous LiCl solution led to atmospheric
      water absorption by the liquid marbles and a consequent mass increase. The liquid
      marbles can be transformed into polymeric capsules containing water by exposure
      to solvent vapor: the PDEA-PS particles were plasticized with the solvent vapor
      to form a polymer film at the air-water interface of the liquid marbles. The
      polymeric capsules with aqueous volumes of 250 MUL or less kept their oblate
      ellipsoid/near spherical shape even after complete water evaporation, which
      confirmed that a rigid polymeric capsule was successfully formed. Both the rate
      of water evaporation from the pure water liquid marbles and the rate of water
      adsorption into the aqueous LiCl liquid marbles were reduced with an increase of
      solvent vapor treatment time. This suggests that the number and size of pores
      within the polymer particles/flocs on the liquid marble surface decreased due to
      film formation during exposure to organic solvent vapor. In addition, organic
      inorganic composite capsules and colloidal crystal capsules were fabricated from
      liquid marbles containing aqueous SiO2 dispersions. 

PMID- 24588748
TI  - Assessment of adolescents' motivation for educational attainment.
AB  - The Adolescent Motivation for Educational Attainment Questionnaire is a 32-item
      questionnaire (we drew 20 items from 3 subscales of the Educational Motivation
      Questionnaire; Murdock, 1999) that was developed to measure multiple potential
      dimensions of adolescents' motivation to complete high school and enroll in post
      secondary education, including competence and effort beliefs; perceived value of
      education; and peer, teacher, and parent support for educational attainment. We
      assessed a multiethnic sample (N = 569) of low-achieving students who started 1st
      grade together in 1 urban and 2 small city school districts. Participants were
      assessed over 2 consecutive years (Grades 8 and 9 given prior grade retention, or
      Grades 9 and 10 if not retained). Exploratory factor analyses identified 4
      correlated dimensions underlying the questionnaire responses. Subsequent
      confirmatory factor analyses provided support for a bifactor model, which
      includes a general factor of students' basic educational motivation, and specific
      factors of (a) teacher educational expectations, (b) peer aspirations, and (c)
      value of education. Measurement invariance of the bifactor model was established
      across students' gender and ethnicity (Caucasian, African American, and Hispanic)
      and year of testing. Criterion-related validity of the general and specific
      factors with students' school belonging, student-teacher warmth and conflict,
      disciplinary practices, letter grade, conduct problems, and behavioral engagement
      was examined. Practical implications of the measure are discussed.

PMID- 24588750
TI  - Effects of PEGylation on membrane and lipopolysaccharide interactions of host
      defense peptides.
AB  - Effects of poly(ethylene glycol) (PEG) conjugation on peptide interactions with
      lipid membranes and lipopolysaccharide (LPS) were investigated for KYE28
      (KYEITTIHNLFRKLTHRLFRRNFGYTLR), an antimicrobial and anti-inflammatory peptide
      derived from human heparin cofactor II. In particular, effects of PEG length and
      localization was investigated by ellipsometry, circular dichroism, nanoparticle
      tracking analysis, and fluorescence/electron microscopy. PEGylation of KYE28
      reduces peptide binding to lipid membranes, an effect accentuated at increasing
      PEG length, but less sensitive to conjugation site. The reduced binding causes
      suppressed liposome leakage induction, as well as bacterial lysis. As a result of
      this, the antimicrobial effects of KYE28 is partially lost with increasing PEG
      length, but hemolysis also strongly suppressed and selecticity improved. Through
      this, conditions can be found, at which the PEGylated peptide displays
      simultaneously efficient antimicrobial affects and low hemolysis in blood.
      Importantly, PEGylation does not markedly affect the anti-inflammatory effects of
      KYE28. The combination of reduced toxicity, increased selectivity, and retained
      anti-inflammatory effect after PEGylation, as well as reduced scavenging by serum
      proteins, thus shows that PEG conjugation may offer opportunities in the
      development of effective and selective anti-inflammatory peptides. 

PMID- 24588751
TI  - P2Y12 platelet function assay for assessment of bleeding risk in coronary artery
      bypass grafting.
AB  - BACKGROUND: The use of platelet function testing has been advocated to
      individualize the time needed between discontinuation of P2Y12 inhibitors and
      coronary artery bypass grafting (CABG). However, the use of specific point-of
      care assays to predict bleeding risk in patients on P2Y12 inhibitors prior to
      CABG has not been fully validated. METHODS: From September 2012 to May 2013, 81
      patients on P2Y12 inhibitors underwent isolated CABG. Preoperative level of P2Y12
      receptor blockade was measured using the VerifyNow P2Y12 assay. Packed red blood
      cell (pRBC) and platelet transfusions and postoperative chest tube output were
      correlated with preoperative P2Y12 reaction units (PRUs). RESULTS: Patients who
      stopped P2Y12 inhibitors for <=3 days received significantly more platelet
      transfusions as compared to those whose inhibitors were stopped for longer (0.71
      +/- 1.05 units vs. 0.20 +/- 0.71 units, p = 0.01). They also had increased
      postoperative chest tube output (552.5 +/- 325.5 mL vs. 399.8 +/- 146.5 mL, p =
      0.03). There was no significant difference in platelet transfusions and chest
      tube output between patients whose preoperative PRU value was <250 compared to
      those whose values were >=250. pRBC requirements were correlated with
      preoperative hematocrit and age but not with timing of discontinuation of P2Y12
      inhibitors or with PRU levels. CONCLUSIONS: In patients on P2Y12 inhibitors
      undergoing CABG surgery, discontinuation of P2Y12 inhibitors three days prior to
      surgery rather than VerifyNow PRU values predicts postoperative bleeding and the
      need for platelet transfusions. Sole reliance on platelet function testing to
      determine the timing of surgery for patients on P2Y12 inhibitors should therefore
      be done with caution.

PMID- 24588752
TI  - Synthesis and antiviral evaluation of novel 2',2'-difluoro 5'-norcarbocyclic
      phosphonic acid nucleosides as antiviral agents.
AB  - A very efficient synthetic route to novel 2',2'-difluoro 5'-norcarbocyclic
      phosphonic acid nucleosides from but-3-en-1-ol 5 is described. The discovery of
      2'-fluorinated furanose nucleoside 1 as a potent anti-HIV-1 agent has led to the
      synthesis and biological evaluation of 2'-modified 5'-norversions of the
      carbocyclic phosphonate nucleosides. The synthesized nucleoside analogues 18, 19,
      23a, 23b, and 24 were tested for anti-HIV activity as well as cytotoxicity.
      Adenine analogue 19 shows significant anti-HIV-1 activity (EC(50) = 13 MUM).

PMID- 24588753
TI  - Nucleotide sequences of an important functional gene hnRNPA2/B1 from Ailuropoda
      melanoleuca and Ursus thibetanus mupinensis and its potential value in
      phylogenetic study.
AB  - The cDNA fragments of hnRNPA2/B1 were cloned from the giant panda and black bear
      using RT-PCR method, which were, respectively, 1029bp and 1026bp in length
      encoding 343 and 341 amino acids. Analysis indicated the cDNA cloned from the
      giant panda encoded variant B1 while the cDNA cloned from black bear encoded
      variant A2. Analyzing the hnRNPA2B1 peptide of the giant panda and black bear, 76
      glycine residues and 86 glycine residues were, respectively, found, and moreover,
      most glycine are concentrated in the latter halves of the hnRNPA2B1 peptides.
      Functional sites prediction also showed many N-myristoylation sites existed in
      the glycine-rich domain, which is probably related to the role of telomere
      maintenance. From base bias and substitution analysis, we can conclude that the
      ORF of hnRNPA2/B1 biased G while hated C, and transition of the third site did
      not achieve the level of saturation. Orthology analysis indicated that both the
      nucleotide sequence and the deduced amino acid sequence showed high identity to
      other 26 hnRNPA2/B1 sequences from mammals and nonmammals reported. These
      sequences were used to construct phylogenetic trees employing the NJ method with
      1000 bootstrap, and the obtained tree demonstrated similar topology with the
      classical systematics, which suggested the potential value of hnRNPA2/B1 in
      phylogenetic analysis. This report will be the first step to the study function
      of hnRNPA2/B1 in the giant panda and black bear, and will provide a scientific
      basis to disease surveillance, captive breeding, and conservation of the
      endangered species. 

PMID- 24588754
TI  - Structural evaluation of the DNA aptamer for ATP DH25.42 by AFM.
AB  - Atomic force microscopy (AFM) can dynamically detect the adhesion or affinity
      force between a sample surface and a cantilever. This feature could be used to
      analyze bio-molecular interactions between a DNA aptamer and a target molecule.
      In this study, the binding force between adenosine triphosphate (ATP) and the
      anti-ATP DNA aptamer DH25.42, based on structural changes was measured using AFM.
      In addition, the relationship between the cations in the binding buffer, and the
      affinity and structure formation of the DNA aptamer was also evaluated using AFM
      and circular dichroism (CD) spectrum analysis. As a result, the specific force
      between DH25.42 and ATP could be measured by AFM. Moreover, it was suggested that
      Mg(2+) in the binding buffer was critical to the binding function of DH25.42 to
      ATP. 

PMID- 24588755
TI  - Synthesis of capped RNA using a DMT group as a purification handle.
AB  - We report a new method for synthesis of capped RNA or 2'-OMe RNA that uses a N(2
      )4,4'-dimethoxytrityl (DMT) group as a lipophilic purification handle to allow
      convenient isolation and purification of the capped RNA. The DMT group is easily
      removed under mild conditions without degradation of the cap. We have used this
      approach to prepare capped 10- and 20-mers. This method is compatible with the
      many condensation reactions that have been reported for preparation of capped RNA
      or cap analogues. 

PMID- 24588756
TI  - Accelerated intensity frailty model for recurrent events data.
AB  - In this article we propose an accelerated intensity frailty (AIF) model for
      recurrent events data and derive a test for the variance of frailty. In addition,
      we develop a kernel-smoothing-based EM algorithm for estimating regression
      coefficients and the baseline intensity function. The variance of the resulting
      estimator for regression parameters is obtained by a numerical differentiation
      method. Simulation studies are conducted to evaluate the finite sample
      performance of the proposed estimator under practical settings and demonstrate
      the efficiency gain over the Gehan rank estimator based on the AFT model for
      counting process (Lin et al., 1998). Our method is further illustrated with an
      application to a bladder tumor recurrence data.

PMID- 24588757
TI  - A method for the automated long-term monitoring of three-spined stickleback
      Gasterosteus aculeatus shoal dynamics.
AB  - This paper describes and evaluates a flexible, non-invasive tagging system for
      the automated identification and long-term monitoring of individual three-spined
      sticklebacks Gasterosteus aculeatus. The system is based on barcoded tags, which
      can be reliably and robustly detected and decoded to provide information on an
      individual's identity and location. Because large numbers of fish can be
      individually tagged, it can be used to monitor individual- and group-level
      dynamics within fish shoals. 

PMID- 24588758
TI  - 'A place for men to come and do their thing': constructing masculinities in
      betting shops in London.
AB  - During fieldwork conducted with workers and customers in betting shops in London
      research participants consistently conceptualized betting shops as masculine
      spaces in contrast to the femininity of other places including home and the bingo
      hall. According to this argument, betting on horses and dogs was 'men's business'
      and betting shops were 'men's worlds'. Two explanations were offered to account
      for this situation. The first suggested that betting was traditionally a pastime
      enjoyed by men rather than women. The second was that betting is intrinsically
      more appealing to men because it is based on calculation and measurement, and
      women prefer more intuitive, simpler challenges. I use interviews with older
      people to describe how the legalisation of betting in cash in 1961 changed the
      geography of betting. I then draw upon interviews with regular customers in order
      to show how knowledge about betting is shared within rather than between genders.
      Finally, I use my experience of training and working as a cashier to describe how
      the particular hegemonic masculinity found in betting shops in London is
      maintained through myriad everyday practices which reward certain kinds of
      gendered performances while at the same time suppressing alternatives. The
      article shows how particular spaces may become gendered as an unanticipated
      consequence of legislation and how contingent gendered associations are both
      naturalized and, at the same time, subjected to intense attention. 

PMID- 24588759
TI  - Compassion-focused therapy: Preface and introduction for special section.

PMID- 24588760
TI  - The origins and nature of compassion focused therapy.
AB  - Compassion focused therapy (CFT) is rooted in an evolutionary, functional
      analysis of basic social motivational systems (e.g., to live in groups, form
      hierarchies and ranks, seek out sexual, partners help and share with alliances,
      and care for kin) and different functional emotional systems (e.g., to respond to
      threats, seek out resources, and for states of contentment/safeness). In
      addition, about 2 million years ago, (pre-)humans began to evolve a range of
      cognitive competencies for reasoning, reflection, anticipating, imagining,
      mentalizing, and creating a socially contextualized sense of self. These new
      competencies can cause major difficulties in the organization of (older)
      motivation and emotional systems. CFT suggests that our evolved brain is
      therefore potentially problematic because of its basic 'design,' being easily
      triggered into destructive behaviours and mental health problems (called 'tricky
      brain'). However, mammals and especially humans have also evolved motives and
      emotions for affiliative, caring and altruistic behaviour that can organize our
      brain in such a way as to significantly offset our destructive potentials. CFT
      therefore highlights the importance of developing people's capacity to
      (mindfully) access, tolerate, and direct affiliative motives and emotions, for
      themselves and others, and cultivate inner compassion as a way for organizing our
      human 'tricky brain' in prosocial and mentally healthy ways.

PMID- 24588761
TI  - A meta-analysis and theoretical critique of oxytocin and psychosis: prospects for
      attachment and compassion in promoting recovery.
AB  - OBJECTIVES: There is now considerable evidence that affiliative processes are
      linked to oxytocin (OXT), which is linked to a range of social-cognition
      competences underpinning interpersonal functioning. There is evidence that OXT
      circuitry is involved in psychosis and emerging evidence for OXT in treatment.
      Therefore, this study explored studies investigating OXT and improvements in
      symptoms and social cognition among individuals diagnosed with psychosis. METHOD:
      We conducted a systematic review of randomized controlled trials investigating
      OXT and psychosis. Specifically we asked, (1) what is the evidence that OXT is
      associated with improved overall, positive, negative and general symptoms and (2)
      what is the evidence that OXT is associated with improved social cognition?
      RESULTS: There were seven randomized controlled trials that met the inclusion
      criteria for this review. We conducted an exploratory meta-analysis of data from
      four of these studies on a total sample size of n = 105. For overall symptoms,
      using a random-effects model OXT versus placebo was associated with an effect
      size of d = 0.52 (95% CI = 0.34-0.70; z = 5.66; p < .01). There was evidence of
      significant heterogeneity (Q = 96.4, p < .001; I(2) = 96.5%). Similar patterns of
      findings were observed for positive, negative, and general symptoms. We found
      significant evidence of high risk of bias across all studies. We also identified
      that one particular study had an undue effect on overall effect size estimates.
      Finally, evidence regarding OXT was linked to improved social cognition was
      inconsistent. CONCLUSIONS: There are significant problems in interpreting the
      current evidence base for OXT in psychosis. However, OXT may provide a useful
      biomarker for exploring mechanisms of change occurring in psychological therapies
      including compassion-focused therapy (CFT), which through its engagement of the
      attachment system may directly influence OXT.

PMID- 24588762
TI  - The development and application of compassion-focused therapy for eating
      disorders (CFT-E).
AB  - OBJECTIVES: This article outlines specific developments in compassion-focused
      therapy (CFT) for the treatment of patients with an eating disorder. METHODS: The
      article provides a narrative review based on the existing literature and current
      practices of CFT for eating disorders (CFT-E). RESULTS: The role of shame, self
      criticism, self-directed hostility, and difficulties in generating and
      experiencing affiliative emotion in patients with an eating disorder is
      highlighted. The article describes how CFT-E uniquely addresses these issues and
      discusses the current evidence base for CFT-E. It also provides an outline of
      recent and potential future developments in CFT-E. CONCLUSIONS: CFT-E offers a
      promising treatment for adult outpatients who present to specialist eating
      disorder services with restricting and binge/purging eating disorders. Recent
      developments include treatment protocols for patients who are low weight and have
      an eating disorder and for those presenting with obesity.

PMID- 24588763
TI  - A compassionate-focused therapy group approach for acute inpatients: feasibility,
      initial pilot outcome data, and recommendations.
AB  - OBJECTIVES: This study aimed to examine the feasibility of running and evaluating
      a compassion-focused therapy (CFT) group adapted for acute inpatient settings,
      characterized by unpredictable lengths of admission, presentations, and
      diagnoses. DESIGN AND METHODS: This pilot project used a mixed methods design to
      assess the impact of offering CFT-informed group sessions on an acute inpatient
      unit. Pre- and post-session ratings of distress and calmness, and ratings of
      understanding and helpfulness, were gathered from participants over a 6-month
      period. Semi-structured interviews were conducted with four participants to
      gather their experience of the group. RESULTS: Fifty-seven complete sets of
      rating measures were generated from 82 participants recruited for the study
      (attrition rate 30%), from a total pool of 93 inpatients attending group
      sessions. Pre- to post-CFT session data highlighted a significant decrease in
      distress ratings and a significant increase in calmness ratings. A thematic
      analysis of four interviews identified themes relating to understanding
      compassion, experience of positive affect, and the experience of common humanity.
      CONCLUSIONS: This is the first attempt to explore the effects of a CFT-informed
      approach in acute mental health settings. These groups were well received by
      staff and patients, with some therapeutic impact despite being comparatively
      short and set against the background of a busy inpatient ward. These groups can
      be open and transdiagnostic, with stand-alone topics and practices having
      positive impacts on distress and calmness. Future studies need to focus on
      adapting content and pacing for this group of people based on ongoing feedback
      from participants.

PMID- 24588764
TI  - The validation of the self-report strengths and difficulties questionnaire for
      use by 6- to 10-year-old children in the U.K.
AB  - OBJECTIVE: To examine the factor structure of the self-report Strengths and
      Difficulties Questionnaire (SDQ) for data from a sample of British children aged
      6-10 years. METHOD: The self-report SDQ was administered to 900 children aged 6
      10 years via interviews with trained counsellors. RESULTS: Confirmatory and
      exploratory factor analyses showed that a two-factor solution comprising
      'externalizing and peer problems' and 'internalizing problems' fit the data well
      for both the 6- to 7- and 8- to 10-year-old samples. The factors were correlated
      in both samples. CONCLUSIONS: Children between 6 and 10 years of age provided
      meaningful SDQ data. The identified two-factor model maps broadly onto the
      constructs of externalizing and internalizing behaviour.

PMID- 24588766
TI  - Stathmin, interacting with Nf-kappaB, promotes tumor growth and predicts poor
      prognosis of pancreatic cancer.
AB  - Stathmin (STMN) has been known as a p53-regulated protein and has been shown to
      play an oncogenic role in a range of human malignancies. Paradoxically, most
      recent studies demonstrated that stathmin has a dual function as both an oncogene
      and a metastasis suppressor. Stathmin is a member of microtubule dynamic
      destabilizing proteins and stathmin-regulated microtubule disruption could lead
      to a variety of cell dysfunctions such as enhanced chronic hypoxia in pancreatic
      cancer. In this study, we identified that stathmin promotes proliferation of
      pancreatic cancer cells by an underlying nuclear factor kappa B (Nf-kappaB)
      interacting mechanism. In human specimens, stathmin was significantly
      overexpressed in pancreatic cancer tissues and high expression of stathmin was
      correlated with vascular emboli (p=0.028), tumor size (p=0.019), and overall
      survival (p=0.031). Functional assays showed that knockdown of stathmin
      significantly reduced pancreatic cancer cell viability, colony formation, and
      arrested the cell cycle at the G2/M phase. Furthermore, silence of stathmin could
      reduce pancreatic tumor growth in nude mice. For the mechanism, Western blot
      analyses demonstrated that Nf-kappaB (p65) was significantly down-regulated when
      stathmin was silenced. In addition, co-immunoprecipitation (CoIP) assay suggested
      that stathmin was able to interact with Nf-kappaB (p65). Our findings indicate
      that stathmin might play its oncogenic role by an interaction with Nf-kappaB
      pathway, which may reveal a novel mechanism to uncover the role of microtubule
      destabilizing stathmin in pancreatic cancer environment as well as provide a
      potential therapeutic strategy for pancreatic cancer. 

PMID- 24588767
TI  - miR-1247 is correlated with prognosis of pancreatic cancer and inhibits cell
      proliferation by targeting neuropilins.
AB  - Accumulating evidence indicates that microRNAs (miRNAs) have great potential as
      tumor biomarkers and therapeutic agents owing to their functions in tumorigenesis
      and cancer progression. Aberrant expression of miR-1247 has been found in several
      cancers and is predicted to play an important role in the pathological processes
      of pancreatic cancer by miRNA-regulated network analysis. We investigated the
      expression profile of miR-1247 in pancreatic cancer tissue microarray by in situ
      hybridization and found that miR-1247 was significantly down-regulated in
      pancreatic cancer tissues compared to matched benign tissues. High levels of miR
      1247 expression were positively correlated with higher overall and recurrence
      free survival in pancreatic cancer patients, while negatively correlated with
      tumor grade. Using in vitro and in vivo models, we demonstrated that increased
      expression of miR-1247 inhibited proliferation, tumorigenicity, colony formation
      and triggered G0/G1 cell cycle arrest in pancreatic cancer cells. Moreover, we
      confirmed that neuropilin1 (NRP1) and neuropilin2 (NRP2) are direct targets of
      miR-1247 by western blot and luciferase reporter assay. Further studies indicated
      that low dose all trans retinoic acid (ATRA) can induce redifferentiation and
      restoration of miR-1247 in pancreatic cancer cells. These findings suggest that
      miR-1247, a novel tumor suppressor, can act as a potential biomarker and
      therapeutic agent for pancreatic cancer. 

PMID- 24588768
TI  - miR-143: a novel regulator of MyoD expression in fast and slow muscles of
      Siniperca chuatsi.
AB  - The fast and slow skeletal muscle fibers in fish are separated to a much greater
      degree than in mammals. MyoD is required for the maintenance of normal fiber type
      balance in muscles. So far, the upstream regulatory factors of MyoD in terms of
      controlling muscle phenotype are poorly understood. In the present study, we used
      Siniperca chuatsi as a model system and demonstrated that miR-143 expression was
      negatively correlated with MyoD expression in the fast and slow muscles of S.
      chuatsi. The luciferase reporter assay further verified the direct interaction
      between the miR-143 and MyoD. The miR-143 suppression also led to the significant
      increase in MyoD and fast myosin heavy chain gene expression in vivo. Taken
      together, our studies indicated that miRNA participates in controlling the
      performance of different muscle fiber types in vertebrates. 

PMID- 24588769
TI  - Chiral phase transfer and enantioenrichment of thiolate-protected Au102 clusters.
AB  - The Au102(p-MBA)44 cluster (p-MBA: para-mercaptobenzoic acid) is observed as a
      chiral compound comprised of achiral components in its single-crystal structure.
      So far the enantiomers observed in the crystal structure are not isolated, nor is
      the circular dichroism spectrum known. A chiral phase transfer method is
      presented which allows partial resolution of the enantiomers by the use of a
      chiral ammonium bromide, (-)-1R,2S-N-dodecyl-N-methylephedrinium bromide ((-)
      DMEBr). At sufficiently low concentration of (-)-DMEBr, the phase transfer from
      water to chloroform is incomplete. Both the aqueous and organic phases show
      optical activity of near mirror image relationship. Differences in the spectra
      are ascribed to the formation of diastereomeric salts. At high concentrations of
      (-)-DMEBr, full phase transfer is observed. The organic phase, however, still
      displays optical activity. We assume that one of the diastereomers has very
      strong optical activity, which overrules the cancelation of the spectra with
      opposite sign. Comparison with computations further corroborates the experimental
      data and allows a provisional assignment of handedness of each fraction. 

PMID- 24588770
TI  - Identification of multiple mercury sources to stream sediments near Oak Ridge,
      TN, USA.
AB  - Sediments were analyzed for total Hg concentration (THg) and isotopic composition
      from streams and rivers in the vicinity of the Y-12 National Security Complex
      (Y12) in Oak Ridge, TN (USA). In the stream directly draining Y12, where
      industrial releases of mercury (Hg) have been documented, high THg (3.26 to 60.1
      MUg/g) sediments had a distinct Hg isotopic composition (delta(202)Hg of 0.02 +/-
      0.150/00 and Delta(199)Hg of -0.07 +/- 0.030/00; mean +/- 1SD, n = 12) compared
      to sediments from relatively uncontaminated streams in the region (delta(202)Hg =
      -1.40 +/- 0.060/00 and Delta(199)Hg of -0.26 +/- 0.030/00; mean +/- 1SD, n = 6).
      Additionally, several streams that are nearby but do not drain Y12 had sediments
      with intermediate THg (0.06 to 0.21 MUg/g) and anomalous delta(202)Hg (as low as 
      5.070/00). We suggest that the low delta(202)Hg values in these sediments provide
      evidence for the contribution of an additional Hg source to sediments, possibly
      derived from atmospheric deposition. In sediments directly downstream of Y12 this
      third Hg source is not discernible, and the Hg isotopic composition can be
      largely explained by the mixing of low THg sediments with high THg sediments
      contaminated by Y12 discharges. 

PMID- 24588771
TI  - Inhibiting enhancer of zeste homolog 2 promotes cellular senescence in gastric
      cancer cells SGC-7901 by activation of p21 and p16.
AB  - Cellular senescence, which can be defined as a stress response preventing the
      propagation of cells that have accumulated potentially oncogenic alterations, is
      invariably associated with a permanent cell cycle arrest. Enhancer of zeste
      homolog 2 (EZH2) as a member of polycomb group proteins and its targets include
      cell cycle regulatory proteins, which govern cell cycle progression and cellular
      senescence. In this study, we report that EZH2 depletion promotes the senescent
      state in human gastric cancer cells SGC-7901. We found that EZH2 functionally
      suppressed the senescent state in human gastric cancer cells SGC-7901. EZH2
      depletion inhibited cell proliferation, arrested cellular cycle, restored
      features of a cellular senescence phenotype, and promoted doxorubicin-induced
      senescence. To prove that EZH2 expression contributes substantially to the change
      of key cell cycle regulators, we showed that p21 and p16 were activated to a
      certain extent upon EZH2 depletion and activation of p21 was in a p53-independent
      manner. Taken together, our data suggest that EZH2 depletion promotes the
      progression of senescence by mediating the activation of tumor suppressor genes
      p21 and p16, and could serve as a potential epigenetic target for gastric cancer
      therapy.

PMID- 24588772
TI  - Understanding the thermal and mechanical stabilities of olivine-type LiMPO4 (M =
      Fe, Mn) as cathode materials for rechargeable lithium batteries from first
      principles.
AB  - To elucidate the microscopic origin of the difference behaviors, first-principles
      calculations were performed to investigate the thermal and mechanical stabilities
      of LixFePO4 and LixMnPO4. The calculated free energies suggested that LiFePO4 and
      LiMnPO4 are thermal stable with respect to relevant oxides both in their pristine
      and fully delithiated states. According to the calculations, it can be identified
      that the shear deformations are more easier to occur with respect to the volume
      compressions in LixFePO4 and LixMnPO4, and this phenomenon is related to M-O(I)
      and M-O(II) bonds. Typically for MnPO4, Li(+) extraction from the host structures
      further weakens the Mn-O(I) bonds by about 33%, and it thus becomes very brittle.
      The shear anisotropy (AG) of MnPO4 is abnormally large and has already reached
      19.05 %, which is about 6 times as large as that of FePO4. Therefore, shear
      deformations and dislocations occur easily in MnPO4. Moreover, as the Mn-O(I)
      bonds in MnPO4 are mainly spread within the {101} and {101} crystal planes, the
      relevant slip systems thus allow the recombination of bonds at the interfaces,
      leading to the experimentally observed phase transformation. It can be concluded
      that mechanical reason will play an important role for the poor cycling
      performance of MnPO4. 

PMID- 24588773
TI  - Effects of hesperidin loaded poly(lactic-co-glycolic acid) scaffolds on growth
      behavior of costal cartilage cells in vitro and in vivo.
AB  - It has been widely accepted that costal cartilage cells (CCs) have more excellent
      initial proliferation capacity than articular cartilage cells. Biodegradable
      synthetic polymer poly(lactic-co-glycolic acid) (PLGA) was approved by Food and
      Drug Administration. Hesperidin has antifungal, antiviral, antioxidant, anti
      inflammatory, and anticarcinogenic properties. Hesperidin loaded (0, 3, 5, and 10
      wt.%) PLGA scaffolds were prepared and in vitro and in vivo properties were
      characterized. Scaffolds were seeded with CCs isolated from rabbit, which were
      kept in culture to harvest for histological analysis. Hesperidin/PLGA scaffolds
      were also implanted in nude mice for 7 and 28 days. Assays of 2-(2-methoxy-4
      nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfo-phenyl)-2H-tetrazolium, monosodium
      salt (WST), and scanning electron microscope were carried out to evaluate
      attachment and proliferation of CCs in hesperidin/PLGA scaffolds.
      Glycosaminoglycan assay was performed to confirm the effects of hesperidin on
      extracellular matrix formation. Reverse-transcriptase polymerase chain reaction
      was carried out to confirm the expression of the specific genes for CCs. In these
      results, we demonstrated that cell attachment and proliferation on
      hesperidin/PLGA scaffolds were more excellent compared with on PLGA scaffold.
      Specially, 5 wt.% hesperidin/PLGA scaffold represented the best results among
      other scaffolds. Thus, 5 wt.% hesperidin/PLGA scaffold will be applicable to
      tissue engineering cartilage. 

PMID- 24588775
TI  - A statistical approach to set classification by feature selection with
      applications to classification of histopathology images.
AB  - Set classification problems arise when classification tasks are based on sets of
      observations as opposed to individual observations. In set classification, a
      classification rule is trained with N sets of observations, where each set is
      labeled with class information, and the prediction of a class label is performed
      also with a set of observations. Data sets for set classification appear, for
      example, in diagnostics of disease based on multiple cell nucleus images from a
      single tissue. Relevant statistical models for set classification are introduced,
      which motivate a set classification framework based on context-free feature
      extraction. By understanding a set of observations as an empirical distribution,
      we employ a data-driven method to choose those features which contain information
      on location and major variation. In particular, the method of principal component
      analysis is used to extract the features of major variation. Multidimensional
      scaling is used to represent features as vector-valued points on which
      conventional classifiers can be applied. The proposed set classification
      approaches achieve better classification results than competing methods in a
      number of simulated data examples. The benefits of our method are demonstrated in
      an analysis of histopathology images of cell nuclei related to liver cancer.

PMID- 24588774
TI  - Postoperative statin use and risk of biochemical recurrence following radical
      prostatectomy: results from the Shared Equal Access Regional Cancer Hospital
      (SEARCH) database.
AB  - OBJECTIVE: To investigate the effect of statin use after radical prostatectomy
      (RP) on biochemical recurrence (BCR) in patients with prostate cancer who never
      received statins before RP. PATIENTS AND METHODS: We conducted a retrospective
      analysis of 1146 RP patients within the Shared Equal Access Regional Cancer
      Hospital (SEARCH) database. Multivariable Cox proportional hazards analyses were
      used to examine differences in risk of BCR between post-RP statin users vs
      nonusers. To account for varying start dates and duration of statin use during
      follow-up, post-RP statin use was treated as a time-dependent variable. In a
      secondary analysis, models were stratified by race to examine the association of
      post-RP statin use with BCR among black and non-black men. RESULTS: After
      adjusting for clinical and pathological characteristics, post-RP statin use was
      significantly associated with 36% reduced risk of BCR (hazard ratio [HR] 0.64,
      95% confidence interval [CI] 0.47-0.87; P = 0.004). Post-RP statin use remained
      associated with reduced risk of BCR after adjusting for preoperative serum
      cholesterol levels. In secondary analysis, after stratification by race, this
      protective association was significant in non-black (HR 0.49, 95% CI 0.32-0.75; P
      = 0.001) but not black men (HR 0.82, 95% CI 0.53-1.28; P = 0.384). CONCLUSION: In
      this retrospective cohort of men undergoing RP, post-RP statin use was
      significantly associated with reduced risk of BCR. Whether the association
      between post-RP statin use and BCR differs by race requires further study. Given
      these findings, coupled with other studies suggesting that statins may reduce
      risk of advanced prostate cancer, randomised controlled trials are warranted to
      formally test the hypothesis that statins slow prostate cancer progression.

PMID- 24588776
TI  - 50 years of the Hungarian Congenital Abnormality Registry.
AB  - The mandatory notification of patients ("cases") with different congenital
      abnormalities (CAs) diagnosed from birth until the end of the first postnatal
      year by medical doctors was ordered by the Ministry of Health in Hungary in 1962
      and this CA-registry was continued as the Hungarian Congenital Abnormality
      Registry (HCAR) based on the international recommendation from 1970. The primary
      objective of the HCAR has been to determine the baseline birth prevalence rate of
      different CAs as reliably as possible, with three secondary objectives: (i) to
      detect temporal and/or spatial clusters of CAs; (ii) to evaluate increasing or
      decreasing time trends of CAs; and (iii) to assist in the planning of medical and
      social services for children and families affected by CA so that appropriate
      resources are allocated efficiently and effectively. This paper summarizes the
      activities and the evolution of the HCAR over the past 50 years (1962-2011)
      including the Hungarian Case-Control Surveillance of Congenital Abnormalities for
      postmarketing surveillance of drug teratogenicity and prevention of CAs; the
      special evaluation of unidentified multiple CAs; the Hungarian Surveillance of
      Germinal Mutations and several international collaborations. In conclusion,
      Hungary enjoyed optimal conditions for the HCAR due to a centralized state health
      system; all deliveries took place in inpatient clinics; the quality of pediatric
      care was high and pediatricians notified most CAs. Autopsy was mandatory in
      infant death, the staff of the HCAR did not consider this CA-registry only as a
      statistical system but the Hungarian Center for Congenital Anomaly Control and
      the Hungarian Case-Control Surveillance of Congenital Abnormalities based on the
      HCAR worked with close collaboration with the parents in order to promote the
      possible good quality of life of their affected children and to prevent their
      risk of recurrence. 

PMID- 24588777
TI  - C677T mutation in methylenetetrahydrofolate reductase gene and neural tube
      defects: should Japanese women undergo gene screening before pregnancy?
AB  - We analyzed the role of maternal C677T mutation in methylenetetrahydrofolate
      reductase (MTHFR) gene on spina bifida development in newborns. A total of 115
      mothers who had given birth to a spina bifida child (SB mothers) gave 10 mL of
      blood together with written informed consent. The genotype distribution of C677T
      mutation was assessed and compared with that of the 4517 control individuals. The
      prevalence of the homozygous genotype (TT) among SB mothers was not significantly
      different from that among the controls (odds ratio [OR] = 0.65; 95% confidence
      interval [CI] = 0.31-1.25; P = 0.182), suggesting that MTHFR 677TT genotype in
      Japan is not associated with spina bifida development in newborns. The T allele
      frequency was not increased in SB mothers (34.8%) as compared to that of the
      control individuals (38.2%). Further, the internationally reported association
      between the two groups was found to be similar in all 15 countries studied except
      the Netherlands, where the TT genotype was found to be a genetic risk factor for
      spina bifida. For the prevention of affected pregnancy every woman planning to
      conceive has to take folic acid supplements 400 MUg a day and the government is
      asked to take action in implementing food fortification with folic acid in the
      near future. In conclusion, it is not necessary for Japanese women to undergo
      genetic screening C677T mutation of the MTHFR gene as a predictive marker for
      spina bifida prior to pregnancy, because the TT genotype is not a risk factor for
      having an affected infant.

PMID- 24588778
TI  - Awareness of and knowledge about mother-to-child infections in Japanese pregnant
      women.
AB  - To reduce the incidence of infants with congenital infections, women should be
      aware of and know prevention measures against maternal infection with mother-to
      child infections during pregnancy. Our objective was to assess the awareness of
      and knowledge about mother-to-child infections in Japanese pregnant women. A
      survey of 343 Japanese pregnant women was completed. Awareness of 13 pathogens
      capable of mother-to-child transmission was surveyed. Knowledge about the
      transmission route, the most susceptible time of infection that may cause severe
      fetal disease during pregnancy, and methods to prevent maternal infection were
      investigated for four major pathogens (cytomegalovirus, rubella virus, Toxoplasma
      gondii, and parvovirus B19) and results were compared between these pathogens.
      The proportion of women aware of pathogens concerning TORCH syndrome was the
      following: rubella virus 76%, Treponema pallidum 69%, Toxoplasma gondii 58%,
      parvovirus B19 28%, herpes simplex virus 27%, and cytomegalovirus 18%. Only 8%
      knew how cytomegalovirus is transmitted, and only 12% knew how parvovirus B19 is
      transmitted; both were significantly lower than those who knew transmission
      routes for rubella virus or Toxoplasma gondii. The proportion of women who knew
      the most susceptible time for severe fetal infection by maternal acquisition of
      cytomegalovirus, Toxoplasma gondii, or parvovirus B19 was significantly lower
      than that for rubella virus. The vast majority of surveyed women were not aware
      of methods to prevent maternal infection with cytomegalovirus or parvovirus B19.
      In conclusion, current awareness of and knowledge about cytomegalovirus and
      parvovirus B19 infection are low in Japanese pregnant women. 

PMID- 24588779
TI  - Follistatin-like 5 is expressed in restricted areas of the adult mouse brain:
      Implications for its function in the olfactory system.
AB  - Follistatin-like 5 (Fstl5), a member of the follistatin family of genes, encodes
      a secretory glycoprotein. Previous studies revealed that other members of this
      family including Fstl1 and Fstl3 play an essential role in development,
      homeostasis, and congenital disorders. However, the in vivo function of Fstl5 is
      poorly understood. To gain insight into the function of Fstl5 in the mouse
      central nervous system, we examined the Fstl5 expression pattern in the adult
      mouse brain. The results of in situ hybridization analysis showed a highly
      restricted pattern of Fstl5, namely, with localization in the olfactory system,
      hippocampal CA3 area and granular cell layer of the cerebellum. Restricted
      expression in the olfactory system suggests a possible role for Fstl5 in
      maintaining odor perception. 

PMID- 24588781
TI  - Validation of otolith daily increments in early juveniles of shanny Lipophrys
      pholis.
AB  - To assess the periodicity of micro-increment formation in otoliths of Lipophrys
      pholis, 90 early juveniles were immersed in alizarin red S or tetracycline
      hydrochloride for 24 h and sacrificed after 10, 20 and 30 days. The number of
      micro-increments viewed under light microscopy was significantly related to the
      duration of the experimental period, and the slopes of the linear regressions
      were not significantly different from 1. This study indicates that micro
      increments in sagittae were deposited daily and can be used as reliable sources
      of age information for L. pholis. 

PMID- 24588780
TI  - A homologation approach to the synthesis of difluorinated cycloalkynes.
AB  - Difluorinated cyclooctynes are important reagents for labeling azido-biomolecules
      through copper-free click chemistry. Here, a safe, scalable synthesis of a
      difluorinated cyclooctyne is reported, which involves a key homologation/ring
      expansion reaction. Sequential ring expansions were also employed to synthesize
      and study a novel difluorinated cyclononyne. 

PMID- 24588782
TI  - Stability and dynamics of the tetravacancy in graphene.
AB  - The relative prevalence of various configurations of the tetravacancy defect in
      monolayer graphene has been examined using aberration corrected transmission
      electron microscopy (TEM). It was found that the two most common structures are
      extended linear defect structures, with the 3-fold symmetric Y-tetravacancy
      seldom imaged, in spite of this being a low energy state. Using density
      functional theory and tight-binding molecular dynamics calculations, we have
      determined that our TEM observations support a dynamic model of the tetravacancy
      under electron irradiation, with Stone-Wales bond rotations providing a mechanism
      for defect relaxation into lowest energy configurations. The most prevalent
      tetravacancy structures, while not necessarily having the lowest formation
      energy, are found to have a local energy minimum in the overall energy landscape
      for tetravacancies, explaining their relatively high occurrence. 

PMID- 24588783
TI  - Intrapericardial teratoma in a newborn.

PMID- 24588784
TI  - Esthetic management of developmental enamel opacities in young permanent
      maxillary incisors with two microabrasion techniques--a split mouth study.
AB  - PURPOSE: This study evaluated the effectiveness of two microabrasion materials
      for the removal of developmental enamel opacities in young permanent maxillary
      incisors. MATERIALS AND METHODS: Using a split-mouth study design, 37% phosphoric
      acid and 18% hydrochloric acid were used for removal of visually unesthetic
      developmental enamel opacities of young permanent maxillary anterior teeth from
      25 subjects (11-13 years old) by two microabrasion techniques for 10 and 5
      seconds respectively. This procedure was repeated four to six times during each
      clinical appointment. The subjects were evaluated about their satisfaction with
      the treatment. Two blinded evaluators appraised both sides of the mouth using
      visual analog scale. The records were analyzed using Wilcoxon test. RESULTS: The
      majority of the subjects (approximately 97%) reported satisfaction at the end of
      the treatment (p = 0.001**). Statistical significant reduction in enamel
      opacities was observed by evaluators immediately after microabrasion technique in
      group 1 (81.75%) and in group 2 (81.4%) (p < 0.002). Reduction was increased to
      97.2% in group 1 and 96.7% in group 2 after 1 month. CONCLUSIONS: Both
      microabrasion techniques showed comparative highly significant successful results
      in esthetic management of enamel opacities clinically and in terms of subject's
      satisfaction. CLINICAL SIGNIFICANCE: Developmental enamel defects like diffuse
      opacities due to high-fluoride content in water and demarcated opacities
      associated with positive dental history and are commonly seen in young permanent
      maxillary incisors of both boys and girls in their developing years. They are
      aware of unesthetic appearance of these newly erupted permanent anterior teeth
      and become highly motivated when informed about minimally invasive, patient
      friendly, cost-effective, and safe treatment like microabrasion for esthetic
      improvement. Both noninvasive microabrasion techniques using 37% phosphoric acid
      (group 1) and 18% hydrochloric acid (group 2) show comparatively high success
      results in treating enamel defects successfully to the subject's satisfaction
      along with their parents.

PMID- 24588785
TI  - Can investments in health systems strategies lead to changes in immunization
      coverage?
AB  - National immunization programs in developing countries have made major strides to
      immunize the world's children, increasing full coverage to 83% of children.
      However, the World Health Organization estimates that 22 million children less
      than five years of age are left unvaccinated, and coverage levels have been
      plateauing for nearly a decade. This paper describes the evidence on factors
      contributing to low vaccination uptake, and describes the connection between
      these factors and the documented strategies and interventions that can lead to
      changes in immunization outcomes. The author suggests that investments in these
      areas may contribute more effectively to immunization coverage and also have
      positive spill-over benefits for health systems. The paper concludes that while
      some good quality evidence exists of what works and may contribute to
      immunization outcomes, the quality of evidence needs to improve and major gaps
      need to be addressed. 

PMID- 24588786
TI  - Human-itarian aid? Two forms of dehumanization and willingness to help after
      natural disasters.
AB  - The present research explores the distinct effects of animalistic and mechanistic
      dehumanization on willingness to help natural disaster victims. We examined
      Japanese and Haitians, two national groups recently struck by earthquakes. We
      showed that Italian participants differently dehumanized the two outgroups:
      Japanese were attributed low human nature (dehumanized as automata), whereas
      Haitians were attributed low human uniqueness (dehumanized as animal-like).
      Ninety participants were then randomly assigned to the Japanese or Haitian target
      group condition. Mediation analyses showed that animalistic dehumanization
      decreased willingness to help Haitians, whereas mechanistic dehumanization
      decreased willingness to help Japanese, even when controlling for attitudes.
      Importantly, reduced empathy explained the effects of both forms of
      dehumanization on intergroup helping. 

PMID- 24588787
TI  - Choosing the best method to estimate the energy density of a population using
      food purchase data.
AB  - BACKGROUND: Energy density (ED) is a measure of the energy content of a food
      component or diet relative to a standard unit of weight. Widespread variation in
      ED assessment methodologies exist. The present study aimed to explore the
      feasibility of calculating the ED of the Scottish diet using UK food purchase
      survey data and to identify the most appropriate method for calculating ED for
      use in the development of a Scottish Dietary Goal that captures any socioeconomic
      differences. METHODS: Energy density was calculated using five different methods
      [food; food and milk; food, milk and energy containing (non-alcoholic) beverages;
      food, milk and all non-alcoholic beverages; and all food and beverages]. ED of
      the Scottish diet was estimated for each of the ED methods and data were examined
      by deprivation category. RESULTS: Mean ED varied from 409 to 847 kJ 100 g(-1)
      depending on the method used. ED values calculated from food (847 kJ 100 g(-1) )
      and food and milk (718 kJ 100 g(-1) ) were most comparable to other published
      data, with the latter being a more accurate reflection of all food consumed. For
      these two methods, there was a significant gradient between the most and least
      deprived quintiles (892-807 and 737-696 kJ 100 g(-1) for food and food and milk,
      respectively). CONCLUSIONS: Because the World Cancer Research Fund
      recommendations are based on ED from food and milk, it was considered prudent to
      use this method for policy purposes and for future monitoring work of the
      Scottish Diet to ensure consistency of reporting and comparability with other
      published studies.

PMID- 24588788
TI  - Governing multicultural populations and family life.
AB  - Shortly after coming to power in Britain, the Conservative-Liberal Democratic
      alliance placed family life at the heart of their political agenda, and set out
      their plans to reform adoption. The paper draws upon debates about the reforms
      and considers them in articulation with concerns about health of the nation
      expressed in political pronouncements on 'broken Britain' and the failures of
      'state multiculturalism'. The paper considers the debates about domestic
      (transracial) and intercountry adoption, and uses feminist postcolonial
      perspectives to argue that we can only understand what are expressed as national
      issues within a transnational and postcolonial framework which illuminate the
      processes of state and institutional race-making. The paper analyses three key
      instances of biopower and governmentality in the adoption debates: the
      population, the normalizing family and the individual. The paper argues that we
      need to understand the reforms as part of a wider concern with the 'problem' of
      multicultural belonging, and that the interlocking discourses of nation, family
      and identities are crucial to the constitution and regulation of gendered,
      racialized subjects. 

PMID- 24588789
TI  - Statistical analysis plan for the 'Efficacy of Nitric Oxide in Stroke' (ENOS)
      trial.
AB  - High blood pressure is common during the acute phase of stroke and is associated
      with a poor outcome. However, the management of high blood pressure remains
      unclear. The 'Efficacy of Nitric Oxide in Stroke' trial tested whether
      transdermal glyceryl trinitrate, a nitric oxide donor that lowers blood pressure,
      is safe and effective in improving outcome after acute stroke. Efficacy of Nitric
      Oxide in Stroke is an international multicenter, prospective, randomized, single
      blind, blinded endpoint trial, with funding from the U.K. Medical Research
      Council. Patients with acute ischemic stroke or intracerebral hemorrhage and
      systolic blood pressure 140-220 mmHg were randomized to glyceryl trinitrate or no
      glyceryl trinitrate and, where relevant, to continue or stop prestroke
      antihypertensive therapy. The primary outcome is shift in modified Rankin Scale
      at three-months. Patients or relatives gave written informed (proxy) consent, and
      all sites had research ethics approval. Analyses will be done by intention to
      treat. This paper and attachment describe the trial's statistical analysis plan,
      developed prior to unblinding of date. The statistical analysis plan contains
      design and methods for analyses, and unpopulated tables and figures for the two
      primary publications and some secondary publications. The database will be locked
      in late February 2014 in preparation for presentation of the results in May 2014.
      The data from the trial will improve the precision of the estimates of the
      overall treatment effects (efficacy and safety) of results from completed trials
      of blood pressure management in acute stroke, and provide the first large-scale
      randomized evidence on transdermal glyceryl trinitrate, and of continuing (vs.
      stopping) prestroke antihypertensive medications, in acute stroke.

PMID- 24588790
TI  - Haloemodin as novel antibacterial agent inhibiting DNA gyrase and bacterial
      topoisomerase I.
AB  - Drug-resistant bacterial infections and lack of available antibacterial agents in
      clinical practice are becoming serious risks to public health. We synthesized a
      new class of haloemodins by modifying a traditional Chinese medicine component,
      emodin. The novel haloemodin exerts strong inhibitory activity on bacterial
      topoisomerase I and DNA gyrase, and not on the topoisomerases of human origin. In
      principle, it shows remarkable antibacterial activities against laboratory and
      clinically isolated Gram-positive bacteria, including vancomycin-resistant
      Enterococcus faecium and methicillin-resistant Staphylococcus aureus. We further
      expanded its antibacterial spectrum into against Gram-negative bacteria with the
      assistance of polymyxin B nonapeptide, which helps haloemodin to penetrate
      through the bacterial outer membrane. Finally, the therapeutic effect of
      haloemodin in vivo was confirmed in curing S. aureus-induced keratitis on rabbit
      model. With distinctive structural difference from the antibiotics we used, the
      haloemodins are of value as promising antibacterial pharmacophore, especially for
      combat the infections caused by drug-resistant pathogens. 

PMID- 24588791
TI  - Understanding medication adherence among patients of Turkish descent with type 2
      diabetes: a qualitative study.
AB  - OBJECTIVES: To explore perspectives of Turkish migrants with type 2 diabetes
      mellitus (T2DM) on adherence to oral hypoglycaemic agents (OHA). DESIGN: In-depth
      interviews with 21 T2DM patients of Turkish descent recruited from primary care
      and community sources in Ghent, Belgium, using a theoretical sampling procedure.
      Analysis was guided by a grounded theory approach, using Nvivo 8. RESULTS:
      Respondents reported a multitude of barriers and facilitators of adherence to
      OHA. Some of these barriers are distinctive for T2DM patients of Turkish descent.
      Respondents' causal beliefs about stress and the Belgian climate often led to non
      adherence during less stressful periods, like summer holidays in Turkey. Some
      respondents adjusted their medication use to food intake or during Ramadan
      fasting. Concerns about OHA were the main reason for the widespread use of herbal
      medicine in this sample. The religious framework used to interpret diabetes led,
      in combination with feelings of depression, to non-adherence in some respondents
      while it facilitated medication adherence in others. A potential gender effect
      with respect to the self-management of OHA was observed. Non-distinctive factors
      include: beliefs about OHA, polypharmacy, beliefs about the course of diabetes,
      forgetfulness, the perception of the doctor's medical expertise, feelings of
      depression and social support. CONCLUSION: Health care providers should explore
      in detail and regularly patients' perspectives on illness beliefs, medication
      beliefs and their trust in doctors' medical expertise as this will provide useful
      starting points for promoting medication adherence. Whenever possible health care
      workers should engage with their patients in therapeutic alliances.

PMID- 24588792
TI  - Contribution of bone marrow-derived mesenchymal stem cells to the morphological
      changes in the bladder after partial outlet obstruction: a preliminary study.
AB  - OBJECTIVES: To investigate the contribution of bone marrow-derived mesenchymal
      stem cells to the changes in bladder morphology in response to partial bladder
      outlet obstruction. METHODS: Allogenic bone marrow cells were transplanted from
      transgenic rats expressing green fluorescent protein into female Sprague-Dawley
      rats 1 day after their bone marrow-derived mesenchymal stem cells had been
      destroyed by irradiation. This generated chimeric rats in which green fluorescent
      protein labeled bone marrow-derived mesenchymal stem cells replaced host bone
      marrow-derived mesenchymal stem cells. The animals received partial bladder
      outlet obstruction or sham surgery 6 weeks later. The animals were killed 6 weeks
      after the surgery, and bladder tissue was prepared for immunofluorescence with
      antibodies against a urothelium marker (AE1/AE3), a myofibroblast marker
      (vimentin), a smooth muscle marker and green fluorescent protein. RESULTS: More
      labeled bone marrow-derived mesenchymal stem cells were found in the partial
      bladder outlet obstruction group than in the in the sham group. Most bone marrow
      derived mesenchymal stem cells were present around the basement membrane
      (laminin) and lamina propria below the urothelium. Bone marrow-derived
      mesenchymal stem cells were also found in the urothelium layer, and some of them
      were double-stained with green fluorescent protein and AE1/AE3. Some bone marrow
      derived mesenchymal stem cells, which were located in the interstitial tissue,
      were double-stained with green fluorescent protein and vimentin. Bone marrow
      derived mesenchymal stem cells, which migrated into the smooth muscle layer,
      showed fusiform morphology, and some were double-stained with green fluorescent
      protein and smooth muscle marker. CONCLUSIONS: Bone marrow-derived mesenchymal
      stem cells home to the partial bladder outlet obstruction bladder, and these
      cells have the potential to differentiate into the several components of bladder
      tissue including the urothelium, myofibroblasts and smooth muscle cells. Thus,
      bone marrow-derived mesenchymal stem cells contribute to the morphological
      changes of the bladder in response to partial bladder outlet obstruction.

PMID- 24588793
TI  - Free-standing Na(2/3)Fe(1/2)Mn(1/2)O(2)@graphene film for a sodium-ion battery
      cathode.
AB  - The development of high-performance cathodes for sodium-ion batteries remains a
      great challenge, while low-cost, high-capacity Na2/3Fe1/2Mn1/2O2 is an attractive
      electrode material candidate comprised of earth-abundant elements. In this work,
      we designed and fabricated a free-standing, binder-free
      Na2/3Fe1/2Mn1/2O2@graphene composite via a filtration process. The porous
      composite led to excellent electrochemical performance due to the facile
      transport for electrons and ions that was characterized by electrochemical
      impedance spectroscopy at different temperatures. The electrode delivered a
      reversible capacity of 156 mAh/g with high Coulombic efficiency. The importance
      of a fluorinated electrolyte additive with respect to the performance of this
      high-voltage cathode in Na-ion batteries was also investigated. 

PMID- 24588794
TI  - Towards a minimal generic set of domains of functioning and health.
AB  - BACKGROUND: The World Health Organization (WHO) has argued that functioning, and,
      more concretely, functioning domains constitute the operationalization that best
      captures our intuitive notion of health. Functioning is, therefore, a major
      public-health goal. A great deal of data about functioning is already available.
      Nonetheless, it is not possible to compare and optimally utilize this
      information. One potential approach to address this challenge is to propose a
      generic and minimal set of functioning domains that captures the experience of
      individuals and populations with respect to functioning and health. The objective
      of this investigation was to identify a minimal generic set of ICF domains
      suitable for describing functioning in adults at both the individual and
      population levels. METHODS: We performed a psychometric study using data from: 1)
      the German National Health Interview and Examination Survey 1998, 2) the United
      States National Health and Nutrition Examination Survey 2007/2008, and 3) the ICF
      Core Set studies. Random Forests and Group Lasso regression were applied using
      one self-reported general-health question as a dependent variable. The domains
      selected were compared to those of the World Health Survey (WHS) developed by the
      WHO. RESULTS: Seven domains of the International Classification of Functioning,
      Disability and Health (ICF) are proposed as a minimal generic set of functioning
      and health: energy and drive functions, emotional functions, sensation of pain,
      carrying out daily routine, walking, moving around, and remunerative employment.
      The WHS domains of self-care, cognition, interpersonal activities, and vision
      were not included in our selection. CONCLUSIONS: The minimal generic set proposed
      in this study is the starting point to address one of the most important
      challenges in health measurement--the comparability of data across studies and
      countries. It also represents the first step in developing a common metric of
      health to link information from the general population to information about sub
      populations, such as clinical and institutionalized populations.

PMID- 24588795
TI  - Surrogates for ocular perfusion pressure are not perfect--authors reply.

PMID- 24588798
TI  - Overturn of the proposed alcohol advertising ban in Lithuania.
AB  - BACKGROUND: In response to the dramatic increase in alcohol-related problems in
      Lithuania, policy measures, including alcohol advertising and availability
      restrictions combined with taxation increase, were implemented in 2007-08.
      Simultaneously, a full alcohol advertising ban was adopted to take effect from 1
      January 2012. Therefore, the alcohol industry responded with extensive lobbying
      aiming to revoke this ban, and ultimately they succeeded at the end of December
      2011. AIM: To document and analyse actions of stakeholders and events during the
      alcohol advertising ban cancellation process in Lithuania. METHODS: Policy
      analysis includes a development of event time-line, description of key
      stakeholders' actions and a review of policy context. FINDINGS: The alcohol
      industry in Lithuania used similar tactics as the tobacco industry globally, such
      as creating strong and diverse opposing groups. The industry successfully exerted
      pressure to change alcohol control legislation, while non-governmental
      organizations had the important role of a watchdog, blunting industry's efforts.
      Unequal power distribution made it difficult to withstand combined local and
      international lobbying to cancel the ban. CONCLUSION: Given the global nature of
      the alcohol industry, there is a need for international regulation to limit the
      influence of vested interests on national lawmaking.

PMID- 24588799
TI  - Effectiveness of KTP laser versus 980 nm diode laser to kill Enterococcus
      faecalis in biofilms developed in experimentally infected root canals.
AB  - This study aimed to evaluate the antibacterial action of KTP (potassium-titanyl
      phosphate) laser irradiations (compared with 980 nm diode laser), associated with
      conventional endodontic procedures, on Enterococcus faecalis biofilms. Fifty-six
      dental roots with single canals were prepared with Ni-Ti rotary instruments,
      autoclaved, inoculated with an E. faecalis suspension and incubated for 72 h.
      They were randomly allocated to control and treatment groups. Laser parameters
      were as follows: power 2.5 W, Ton 35 ms, Toff 50 ms (KTP laser); power 2.5 W, Ton
      30 ms, Toff 30 ms (980 nm diode laser). To evaluate the residual bacterial load,
      BioTimer Assay was employed. The chemo-mechanical treatment together with laser
      irradiations (KTP and 980 nm diode lasers) achieved a considerable reduction of
      bacterial load (higher than 96% and 93%, respectively). Regarding both laser
      systems, comparisons with conventional endodontic procedures (mortality rate of
      about 67%) revealed statistically highly significant differences (P <= 0.01).
      This study confirms that laser systems can provide an additional aid in
      endodontic disinfection.

PMID- 24588800
TI  - MTP -493G>T polymorphism and susceptibility to nonalcoholic fatty liver disease:
      a meta-analysis.
AB  - Microsomal transfer protein (MTP), a lipid transfer protein localized in the
      endoplasmic reticulum of hepatocytes and enterocytes, plays an important role in
      the development of nonalcoholic fatty liver disease (NAFLD). Many existing
      studies have demonstrated that a common polymorphism (-493G>T, rs1800591 G>T) in
      the MTP gene may be implicated in the development and progression of NAFLD, but
      individually published results are inconclusive. This meta-analysis aimed to
      investigate whether MTP -493G>T polymorphism may be a potential risk factor for
      NAFLD. We searched CISCOM, CINAHL, Web of Science, PubMed, Google Scholar, EBSCO,
      Cochrane Library, and CBM databases from inception through October 1, 2013. Meta
      analysis was performed using the STATA 12.0 software. Eleven clinical case
      control studies with a total of 636 NAFLD cases and 918 healthy controls met the
      inclusion criteria. Our meta-analysis results revealed that MTP -493G>T
      polymorphism was strongly correlated with an increased risk of NAFLD. Subgroup
      analysis by ethnicity suggested that MTP -493G>T polymorphism might increase
      individuals' susceptibility to NAFLD among both Caucasian and non-Caucasian
      populations. No publication bias was observed in this meta-analysis. In short,
      the present meta-analysis indicates that MTP -493G>T polymorphisms may contribute
      to individuals' susceptibility to NAFLD. Thus, MTP -493G>T polymorphism may be a
      valuable and practical biomarker for early detection of NAFLD.

PMID- 24588801
TI  - Progress in dialysis practice: an introduction.

PMID- 24588802
TI  - Updates on the management of diabetes in dialysis patients.
AB  - Diabetes mellitus is the leading cause of end-stage renal disease (ESRD) in the
      U.S. and many countries globally. The role of improved glycemic control in
      ameliorating the exceedingly high mortality risk of diabetic dialysis patients is
      unclear. The treatment of diabetes in ESRD patients is challenging, given changes
      in glucose homeostasis, the unclear accuracy of glycemic control metrics, and the
      altered pharmacokinetics of glucose-lowering drugs by kidney dysfunction, the
      uremic milieu, and dialysis therapy. Up to one-third of diabetic dialysis
      patients may experience spontaneous resolution of hyperglycemia with hemoglobin
      A1c (HbA1c) levels <6%, a phenomenon known as "Burnt-Out Diabetes," which remains
      with unclear biologic plausibility and undetermined clinical implications.
      Conventional methods of glycemic control assessment are confounded by the
      laboratory abnormalities and comorbidities associated with ESRD. Similar to more
      recent approaches in the general population, there is concern that glucose
      normalization may be harmful in ESRD patients. There is uncertainty surrounding
      the optimal glycemic target in this population, although recent epidemiologic
      data suggest that HbA1c ranges of 6% to 8%, as well as 7% to 9%, are associated
      with increased survival rates among diabetic dialysis patients. Lastly, many
      glucose-lowering drugs and their active metabolites are renally metabolized and
      excreted, and hence, require dose adjustment or avoidance in dialysis patients. 

PMID- 24588805
TI  - The mitochondrial ATPase6 gene is more susceptible to mutation than the ATPase8
      gene in breast cancer patients.
AB  - BACKGROUND: Breast cancer is the most common malignancy in women throughout the
      world. Mitochondria play important roles in cellular energy production, free
      radical generation and apoptosis. Identification of mitochondrial DNA mutations
      and/or polymorphisms as cancer biomarkers is rapidly developing in molecular
      oncology research. METHODS: In this study, the DNA alterations of the
      mitochondrial ATPase 6 and 8 genes were investigated in 49 breast cancer patients
      using PCR amplification and direct DNA sequencing on mtDNA. A possible
      association between these variants and tumorigenesis was assessed. Furthermore,
      the impact of non-synonymous substitutions on the amino acid sequence was
      evaluated using the PolyPhen-2 software. RESULTS: Twenty eight distinct somatic
      mitochondrial DNA variants were detected in tumor tissues but not in the
      corresponding adjacent non-tumor tissues. Among these variants, 9 were observed
      for the first time in breast cancer patients. The mtDNA variants of A8384 (T7A),
      T8567C (I14T), G8572A (G16S), A9041G (H172R) and G9055A (A177T) showed the most
      significant effects probably due to damaging changes to the resulting protein.
      Furthermore, non-synonymous amino acid changing variants were more frequent in
      the ATPase6 gene compared to the ATPase8 gene. CONCLUSION: Our results showed
      that the ATPase6 gene is more susceptible to variations in breast cancer and may
      play an important role in tumorigenesis by changing the energy metabolism level
      in cancer cells.

PMID- 24588806
TI  - Simulation-based training for prostate surgery.
AB  - OBJECTIVES: To identify and review the currently available simulators for
      prostate surgery and to explore the evidence supporting their validity for
      training purposes. MATERIALS AND METHODS: A review of the literature between 1999
      and 2014 was performed. The search terms included a combination of urology,
      prostate surgery, robotic prostatectomy, laparoscopic prostatectomy,
      transurethral resection of the prostate (TURP), simulation, virtual reality,
      animal model, human cadavers, training, assessment, technical skills, validation
      and learning curves. Furthermore, relevant abstracts from the American Urological
      Association, European Association of Urology, British Association of Urological
      Surgeons and World Congress of Endourology meetings, between 1999 and 2013, were
      included. Only studies related to prostate surgery simulators were included;
      studies regarding other urological simulators were excluded. RESULTS: A total of
      22 studies that carried out a validation study were identified. Five validated
      models and/or simulators were identified for TURP, one for photoselective
      vaporisation of the prostate, two for holmium enucleation of the prostate, three
      for laparoscopic radical prostatectomy (LRP) and four for robot-assisted surgery.
      Of the TURP simulators, all five have demonstrated content validity, three face
      validity and four construct validity. The GreenLight laser simulator has
      demonstrated face, content and construct validities. The Kansai HoLEP Simulator
      has demonstrated face and content validity whilst the UroSim HoLEP Simulator has
      demonstrated face, content and construct validity. All three animal models for
      LRP have been shown to have construct validity whilst the chicken skin model was
      also content valid. Only two robotic simulators were identified with relevance to
      robot-assisted laparoscopic prostatectomy, both of which demonstrated construct
      validity. CONCLUSIONS: A wide range of different simulators are available for
      prostate surgery, including synthetic bench models, virtual-reality platforms,
      animal models, human cadavers, distributed simulation and advanced training
      programmes and modules. The currently validated simulators can be used by
      healthcare organisations to provide supplementary training sessions for trainee
      surgeons. Further research should be conducted to validate simulated
      environments, to determine which simulators have greater efficacy than others and
      to assess the cost-effectiveness of the simulators and the transferability of
      skills learnt. With surgeons investigating new possibilities for easily
      reproducible and valid methods of training, simulation offers great scope for
      implementation alongside traditional methods of training.

PMID- 24588807
TI  - Planting hope in loss and grief: self-care applications of horticultural therapy
      for grief caregivers in Taiwan.
AB  - In 2008, the Taiwan Association for Care and Counseling for Loss organized a
      workshop about Horticultural Therapy, conducted as a participatory action
      research (PAR). Nineteen grief caregivers participated. Specific goals were
      designed according to a survey of participant expectations and focus-group
      discussions. The workshop content included lectures and interactive activities.
      Results demonstrated that most participants displayed an increased awareness of
      personal loss and meaning in grief, indicating that horticulture and nature
      appreciation might relieve individual grief and stress. The report introduces the
      rationale, evolution, execution, and results of the program development. 

PMID- 24588808
TI  - Making heads or tails of mitochondrial membranes in longevity and aging: a role
      for comparative studies.
AB  - Mitochondria play vital roles in metabolic energy transduction, intermediate
      molecule metabolism, metal ion homeostasis, programmed cell death and regulation
      of the production of reactive oxygen species. As a result of their broad range of
      functions, mitochondria have been strongly implicated in aging and longevity.
      Numerous studies show that aging and decreased lifespan are also associated with
      high reactive oxygen species production by mitochondria, increased mitochondrial
      DNA and protein damage, and with changes in the fatty acid composition of
      mitochondrial membranes. It is possible that the extent of fatty acid
      unsaturation of the mitochondrial membrane determines susceptibility to lipid
      oxidative damage and downstream protein and genome toxicity, thereby acting as a
      determinant of aging and lifespan. Reviewing the vast number of comparative
      studies on mitochondrial membrane composition, metabolism and lifespan reveals
      some evidence that lipid unsaturation ratios may correlate with lifespan.
      However, we caution against simply relating these two traits. They may be
      correlative but have no functional relation. We discuss an important methodology
      for body mass and phylogenetic correction in comparative studies. 

PMID- 24588810
TI  - Sublethal amounts of Origanum vulgare L. essential oil and carvacrol cause injury
      and changes in membrane fatty acid of Salmonella Typhimurium cultivated in a meat
      broth.
AB  - This study aimed to evaluate whether sublethal concentrations of the essential
      oil of Origanum vulgare L. (OVEO) and its major compound carvacrol (CAR) cause
      injury to the cell membrane and outer membrane of Salmonella enterica serovar
      Typhimurium ATCC 14028 grown in a meat broth and to assess the effect of these
      substances on membrane fatty acid (FA) composition. Exposure of Salmonella
      Typhimurium ATCC 14028 to sublethal concentrations of OVEO or CAR caused damage
      to the cytoplasmic membrane and outer membrane. OVEO- and CAR-treated cells
      showed lower amounts of saturated FA than nontreated cells. Changes in membrane
      FA composition were mainly related to an increase of C16:1omega7c, C16:1omega7t,
      and C18:2omega6c, and to a decrease of C16:0, C17:0 cyclo, and C19:0 cyclo. These
      results indicate that exposure to sublethal concentrations of OVEO or CAR caused
      sublethal injury Salmonella Typhimurium ATCC 14028 and suggest that an adaptive
      response to these stresses is related to increased synthesis of unsaturated FA
      and cis-trans isomerization.

PMID- 24588809
TI  - Development and antimicrobial susceptibility studies of in vitro monomicrobial
      and polymicrobial biofilm models with Aspergillus fumigatus and Pseudomonas
      aeruginosa.
AB  - BACKGROUND: Mixed microbial infections of the respiratory tracts with P.
      aeruginosa and A. fumigatus capable of producing biofilms are commonly found in
      cystic fibrosis patients. The primary objective of this study was to develop an
      in vitro model for P. aeruginosa and A. fumigatus polymicrobial biofilm to study
      the efficacy of various antimicrobial drugs alone and in combinations against
      biofilm-embedded cells. Simultaneous static cocultures of P. aeruginosa and
      sporelings were used for the development of in vitro P. aeruginosa-A. fumigatus
      polymicrobial biofilm in SD broth in 24-well cell culture plates at 35 degrees C,
      and the biofilm formation was monitored microscopically and
      spectrophotometrically. Using P. aeruginosa-A. fumigatus sporelings cocultures we
      examined the effects of various antimicrobial drugs alone and in combination
      against polymicrobial biofilm by CFU and tetrazolium reduction assays. RESULTS:
      In simultaneous static cocultures P. aeruginosa cells killed A. fumigatus
      conidia, whereas the bacterial cells showed no substantial fungicidal effect on
      sporelings grown for 12 h or longer at 35 degrees C. Monospecies cultures of P.
      aeruginosa produced loosely adhered monomicrobial biofilm and addition of 10%
      bovine serum to the growth medium inhibited the formation of monomicrobial
      biofilm by P. aeruginosa whereas it produced tightly adhered polymicrobial
      biofilm in the presence of A. fumigatus mycelial growth. A. fumigatus produced
      firmly adherent monomicrobial and polymicrobial biofilms. A comparison of CFU and
      MTT assays showed that the latter is unsuitable for studying the effectiveness of
      antimicrobial treatment against polymicrobial biofilm. Tobramycin alone and in
      combination with posaconazole was highly effective against monomicrobial and
      polymicrobial biofilms of P. aeruginosa whereas cefepime alone and in combination
      with posaconazole showed excellent activity against monomicrobial biofilm of P.
      aeruginosa but was less effective against polymicrobial biofilm. Monomicrobial
      and polymicrobial biofilms of A. fumigatus showed similar susceptibility to
      posaconazole with and without the antibacterial drug. CONCLUSIONS: Simultaneous
      static coculture of A. fumigatus sporelings grown for 12 h or longer was superior
      to ungerminated conidia with P. aeruginosa for the development of A. fumigatus-P.
      aeruginosa biofilm. P. aeruginosa-A. fumigatus polymicrobial biofilm shows
      differential susceptibility to antimicrobial drugs whereas the susceptibility of
      A. fumigatus to antimicrobial drugs was unchanged.

PMID- 24588811
TI  - Circulating human microRNAs are not linked to JC polyomavirus serology or urinary
      viral load in healthy subjects.
AB  - BACKGROUND: JC polyomavirus (JCPyV) is a widespread human polyomavirus that
      usually resides latently in its host. It can be reactivated under
      immunomodulating conditions and cause Progressive Multifocal Leukoencephalopathy
      (PML). Circulating microRNAs (miRNAs) are emerging as promising biomarkers for
      several pathologies. In this study, we have investigated whether circulating
      miRNAs exist that are differentially expressed between JCPyV seropositive and
      JCPyV seronegative on the one hand or between JCPyV shedders and JCPyV non
      shedders on the other hand. METHODS: Human miRNA expression profiling was
      performed in a small set of plasma samples obtained from seronegative subjects,
      seropositive shedders and seropositive non-shedders. A set of 10 miRNAs was
      selected for further analysis in a larger group of samples. RESULTS: Based on the
      plasma profiling experiment of 30 samples, 6 miRNAs were selected that were
      possibly differentially expressed between seropositive and seronegative subjects
      and 4 miRNAs were selected that were possibly differentially expressed between
      shedders and non-shedders. Subsequently, expression of these 10 selected miRNAs
      was assessed in an independent set of 100 plasma samples. Results indicated that
      none of them were differentially expressed. CONCLUSION: This study could not
      identify circulating human miRNAs that were differentially expressed between
      plasma from JCPyV seropositive and JCPyV seronegative subjects or between JCPyV
      shedders and JCPyV non-shedders.

PMID- 24588812
TI  - Silicon nutrition alleviates the negative impacts of arsenic on the
      photosynthetic apparatus of rice leaves: an analysis of the key limitations of
      photosynthesis.
AB  - Silicon (Si) plays important roles in alleviating various abiotic stresses. In
      rice (Oryza sativa), arsenic (As) is believed to share the Si transport pathway
      for entry into roots, and Si has been demonstrated to decrease As concentrations.
      However, the physiological mechanisms through which Si might alleviate As
      toxicity in plants remain poorly elucidated. We combined detailed gas exchange
      measurements with chlorophyll fluorescence analysis to examine the effects of Si
      nutrition on photosynthetic performance in rice plants [a wild-type (WT) cultivar
      and its lsi1 mutant defective in Si uptake] challenged with As (arsenite). As
      treatment impaired carbon fixation (particularly in the WT genotype) that was
      unrelated to photochemical or biochemical limitations but, rather, was largely
      associated with decreased leaf conductance at the stomata and mesophyll levels.
      Indeed, regardless of the genotypes, in the plants challenged with As,
      photosynthetic rates correlated strongly with both stomatal (r(2)  = 0.90) and
      mesophyll (r(2)  = 0.95) conductances, and these conductances were, in turn,
      linearly correlated with each other. The As-related impairments to carbon
      fixation could be considerably reverted by Si in a time- and genotype-dependent
      manner. In conclusion, we identified Si nutrition as an important target in an
      attempt to not only decrease As concentrations but also to ameliorate the
      photosynthetic performance of rice plants challenged with As. 

PMID- 24588813
TI  - A mixed-method approach to evaluate a pharmacist intervention for veterans with
      hypertension.
AB  - This paper examines blood pressure (BP) control after 6 months of an intensive
      pharmacist-managed intervention in a mixed-methods randomized controlled trial
      conducted at the Iowa City Veteran Affairs Health Care System and two community
      based outreach clinics. Patients received the pharmacist intervention for the
      first 6 months. The study coordinator conducted a summative evaluation with 37
      patients 18 to 24 months following the initial 6-month intervention period. BP
      was significantly reduced in diabetic patients following an intensive pharmacist
      intervention (-8.0/-4.0 +/- 14.4/9.1 mm Hg systolic/diastolic, P<.001 and P=.001,
      respectively). BP was reduced even more in nondiabetic patients (-14.0/-5.0 +/-
      1.9/10.0 mm Hg, P<.001). Medication adherence significantly improved from
      baseline to 6 months (P=.017). BPs were significantly lower at 6 months following
      an intensive pharmacist intervention. Patients also expressed a high level of
      satisfaction with and preference for co-management of their hypertension, as well
      as other chronic diseases.

PMID- 24588814
TI  - Orthostatic hypotension associated with baroreceptor dysfunction: treatment
      approaches.
AB  - Orthostatic hypotension (OH) is a relatively common heterogeneous and
      multifactorial disorder often caused by autonomic dysfunction. This condition has
      a deleterious impact on quality of life and contributes to higher mortality
      rates. Supine hypertension is very common in patients with autonomic failure,
      limits the use of pressor agents, and can result in end-organ damage. Current
      recommendations on the optimal management of these patients are based on expert
      opinion and poor-quality small cross-sectional studies including patients with
      primary autonomic failure and severe orthostatic hypotension. The authors present
      their treatment approach in 12 patients with disabling orthostatic hypotension
      and supine hypertension not related to primary autonomic failure, presenting to a
      referral center over a 4-year period. The first step is to educate the patient
      about the pathophysiology and course of their disorder. Nonpharmacologic
      therapies and maneuvers are usually effective in relieving symptoms and
      preventing syncope. If needed, pharmacologic options such as fludrocortisones and
      midodrine are also available in patients with severe symptoms. Supine
      hypertension represents a challenge in the treatment of this condition.
      Therefore, elevation of the bed of the head and dosing of short-acting
      antihypertensive agents at bedtime is often indicated. 

PMID- 24588815
TI  - A large cohort study evaluating risk factors associated with uncontrolled
      hypertension.
AB  - Hypertension is the most common primary diagnosis in the United States. Risks for
      long-term consequences such as myocardial infarction, heart failure, stroke, and
      kidney disease continue to significantly increase as long as hypertension remains
      uncontrolled. This retrospective cohort study of 661,075 patients identified with
      uncontrolled hypertension, defined as systolic blood pressure (SBP) >= 140 mm Hg
      and/or diastolic blood pressure (DBP) >= 90 mm Hg, from a large integrated
      healthcare organization was conducted to examine multiple patient characteristics
      to determine their association with uncontrolled hypertension. Multivariate
      analysis revealed that compared with Caucasians, African Americans (odds ratio
      [OR], 1.18; 95% confidence interval [CI], 1.16-1.20) were significantly
      associated with uncontrolled hypertension, as were unpartnered populations (OR,
      1.15; 95% CI, 1.14-1.17), number of antihypertensive medications prescribed (OR,
      1.37; 95% CI, 1.33-1.41), and adherence to most antihypertensive medications. A
      secondary analysis found an association between uncontrolled blood pressure and
      Patient Health Questionnaire-9 (PHQ-9) score (OR, 1.21; 95% CI, 1.16-1.26). Our
      findings suggest that the presence of these identified risk factors recommends a
      commitment to a more aggressive hypertension management program to prevent
      cardiovascular disease caused by uncontrolled hypertension.

PMID- 24588816
TI  - Arterial stiffness parameters in patients with chronic kidney disease.

PMID- 24588817
TI  - Crosstalk between the nervous and the immune systems in health and sickness.

PMID- 24588818
TI  - The pivotal role of nitric oxide: effects on the nervous and immune systems.
AB  - Nitric oxide (NO) has an important role in physiological and pathological
      processes in general, and in particular plays a homeostatic role in the nervous
      and immune systems. The many different physiological functions of NO include
      those of a mediator of blood vessel dilation, neurotransmitter, neuromodulator
      and inductor of mitochondrial biogenesis. In addition, NO can transform into
      highly reactive and harmful molecules producing an impairment of the DNA, lipids
      or proteins, and thus altering their function. This dual action of NO, by which
      it plays an important role in homeostasis and aids the development of
      pathological processes, makes this molecule an interesting target for medical
      therapies, especially with respect to the nervous and immune systems. This review
      describes the multiple roles of NO played out in the nervous and immune systems
      during different physiological and pathophysiological processes. 

PMID- 24588819
TI  - Role of the endocannabinoid system in the neuroendocrine responses to
      inflammation.
AB  - A few years ago the endocannabinoid system has been recognized as a major
      neuromodulatory system whose main functions are to exert and maintain the body
      homeostasis. Several different endocannabinoids are synthesized in a broad class
      of cell types, including those in the brain and the immune system; they bind to
      cannabinoid G-protein-coupled receptors, having profound effects on a variety of
      behavioral, neuroendocrine and autonomic functions. The coordinated neural,
      immune, behavioral and endocrine responses to inflammation are orchestrated to
      provide an important defense against infections and help homeostasis restoration
      in the body. These responses are executed and controlled mainly by the
      hypothalamic-pituitary adrenal axis. Also, the hypothalamic-neurohypophyseal
      system is essential for survival and plays a role recovering the homeostasis
      under a variety of stress conditions, including inflammation and infection. Since
      the endocannabinoid system components are present at sites involved in the
      hypothalamic-pituitary axis regulation, several studies were performed in order
      to investigate the endocannabinoid-mediated neurotransmitters and hormones
      secretion under physiological and pathological conditions. In the present review
      we focused on the endocannabinoids actions on the neuroendocrine response to
      inflammation and infection. We provide a detailed overview of the current
      understanding of the role of the endocannabinoid system in the recovering of
      homeostasis as well as potential pharmacological therapies based on the
      manipulation of endocannabinoid system components that could provide novel
      treatments for a wide range of disorders. 

PMID- 24588820
TI  - Physiology and therapeutic potential of the thymic peptide thymulin.
AB  - Thymulin is a thymic hormone exclusively produced by the epithelial cells of the
      thymus. After its discovery and initial characterization in the '70s, it was
      demonstrated that the production and secretion of thymulin are strongly
      influenced by the neuro-endocrine system. Conversely, a growing body of evidence,
      to be reviewed here, suggests that thymulin is a hypophysiotropic peptide.
      Additionally, a substantial body of information pointing to thymulin and a
      synthetic analog as anti-inflammatory and analgesic peptides in the central
      nervous system brain and other organs will be also reviewed. In recent years, a
      synthetic DNA sequence encoding a biologically active analog of thymulin, metFTS,
      was constructed and cloned in a number of adenovectors. These include
      bidirectional regulatable Tet-Off vector systems that simultaneously express
      metFTS and green fluorescent protein and that can be down-regulated reversibly by
      the addition of the antibiotic doxycycline. A number of recent studies indicate
      that gene therapy for thymulin may be an effective therapeutic strategy to
      prevent some of the hormonal and reproductive abnormalities that typically appear
      in congenitally athymic (nude) mice, used as a suitable model of neuroendocrine
      and reproductive aging. Summing up, this article briefly reviews the publications
      on the physiology of the thymulin-neuroendocrine axis and the anti-inflammatory
      properties of the molecule and its analog. The availability of novel
      biotechnological tools should boost basic studies on the molecular biology of
      thymulin and should also allow an assessment of the potential of gene therapy to
      restore circulating thymulin levels in thymodeficient animal models and
      eventually, in humans. 

PMID- 24588821
TI  - Social neuroeconomics: the influence of microbiota in partner-choice and
      sociality.
AB  - By focusing on the studies of primate behaviour and human neuroscience, we
      describe how different neurological processes are the base of proximate aspects
      of social-decision making. We also review the fact that distinct aspects of
      animal behaviour are not under conscious or abstract control and that instead
      they may be regulated by adaptive 'rules of thumb'. In particular, by describing
      the microbiota- gut-brain axis we elaborate on suggesting that microbiota has an
      influence on within-individual aspects of social decision making and in
      particular facilitating social interactions. Finally, we present comparative
      evidence of the role of microorganisms as modifiers of aspects of kinship,
      reproduction and group-members' recognition, suggesting how microbiota also has
      an influence on between individual aspects of decision making, which are
      themselves primary aspects of cooperation. In summary, we propose that modern
      socioeconomic choice theories may still benefit from alternative theoretical
      frameworks that consider the human being as a complex organism, with intrinsic
      constraints and capacities product of its evolutionary history, and not just as
      an exclusively-cognitive decision maker acting independently of its closest
      partners and commensals: its microbiota.

PMID- 24588822
TI  - The effect of psychological stress and social isolation on neuroimmunoendocrine
      communication.
AB  - The adaptive response to physical or psychological challenges or threats involves
      the modulation of the three regulatory systems: the nervous, endocrine and immune
      systems. Correct communication between these systems is required to maintain a
      homeostatic balance, and to guarantee the health and survival of the individual.
      While the stress response is essential for survival, failure to cope with a
      stress can impair the function of these regulatory systems and prevent effective
      communication between them. Under such circumstances, the loss of homeostasis
      ultimately leads to the development of pathologies that can compromise survival.
      Social species live in groups, the maintenance of which ensures the survival of
      the individual by providing protection from environmental threats. However, the
      disruption of social bonds in such species constitutes a potent emotional stress.
      Thus, social isolation is considered a risk factor for morbidity and mortality.
      The response to isolation or loneliness can vary greatly between individuals due
      to the influence of many factors, some of which will be considered in this
      Review. These factors can exert a significant influence on the three regulatory
      systems throughout the lifespan of the organism, and they include characteristics
      of the stressor itself (e.g., duration), as well as those of the organism (e.g.,
      biological age), in addition to external factors (e.g., environmental events). 

PMID- 24588823
TI  - Crosstalk between behavior and immune system during the prodromal stages of
      Alzheimer's disease.
AB  - The crosstalk in the functional interplay of the neuroimmune system is essential
      to ensure homeostasis preservation and health. Alzheimer's disease (AD) can be
      understood in the context of aging of this neuroimmune communication. AD has an
      important genderdependent component and is benefitted by lifestyle strategies
      such as physical exercise, enriched environments and nutrition. Recently, the
      functional and redox state of peripheral immune cells has been proposed as a
      useful tool for measuring the progression of AD. The present review summarizes
      the relevance of the disruption of crosstalk among neurons, glial cells, immune
      mediators and cells from the very beginning of the prodromal stages of AD, when
      early BPSD symptoms have already started but cognitive function still seems
      apparently normal. The study of the role of neuroimmune system and how its
      disruption contributes to the onset of disease may help in understanding its
      biological mechanisms and in finding behavioral parameters and immunological
      biomarkers for the prodromic phases. Here we present results of 3xTg-AD mice from
      pre-morbid to early-stages of AD and how early BPSD-like symptoms correlate with
      changes in the organometrics of thymus and spleen that are indirect indicators of
      the immunological status. These functional relationships between behavioral and
      peripheral system also revealed the existence of differences between biological
      and chronological ages (an advanced biological age) since the prodromal stages.
      Overall, the data available suggest that the crosstalk between behavior (nervous)
      and immune system plays an important role since prodromal stages of AD. 

PMID- 24588824
TI  - Neuroendocrine stimulation of mucosal immune cells in inflammatory bowel disease.
AB  - Crohn's disease and ulcerative colitis are the major inflammatory bowel diseases
      (IBD) in humans. With the incidence of increasing world-wide, it currently
      affects 4 million people in Europe and in the USA. It is an idiopathic, chronic
      relapsing intestinal disorder of complex pathogenesis. The etiology of both
      diseases remains unknown, but recent data suggest that they appear in genetically
      predisposed individuals, because of an exaggerated mucosal immune response to
      commensal microbiota present in the gut. There is increasing evidence for an
      alteration of the immune regulation mechanisms in patients, with mucosal T
      lymphocytes playing a crucial role in the pathogenic events leading to tissue
      damage. It is clear that the disease is the result of environmental factors
      acting on genetically predisposed individuals. In humans, psychological trauma,
      stress or depression, have been involved as precipitating or relapsing factors of
      the disease, although this link remains elusive. However, several published works
      using colitis animal models subjected to stress conditions, have given consistent
      proof as to the molecular link between emotional stress, increase in epithelial
      permeability, alteration of the gut microflora composition and activation of pre
      sensitized T lymphocytes. Gaining knowledge of the cross talk between components
      of the brain - gut - immune system axis may be fruitful in the design of future
      therapeutic approaches, such as the use of vasointestinal peptide (VIP) in this
      pathology. 

PMID- 24588825
TI  - Neuroimmune interactions and psychologycal stress induced by cohabitation with a
      sick partner: a review.
AB  - This study reviews the neuroimmunological consequences elicited in mice from long
      term cohabitation with tumor-bearing conspecifics. Two types of experiments were
      performed; one used Swiss female mice and Ehrlich tumor cells, and the other used
      C57Bl/6 female mice and B16F10 melanoma cells. The female Swiss mice and the
      C57Bl/6 mice were divided into two groups, i.e., control and experimental. One
      mouse in each control pair was treated with control solutions (1.0 mL/kg); the
      other was kept undisturbed and called the 'companion of health partner' (CHP).
      One mouse in each experimental pair was inoculated with 5 x 10(6) Ehrlich tumor
      cells or with 10(6) murine B16-F10 melanoma cells; the other mouse, which was the
      subject of the performed studies, was left undisturbed and called the 'companion
      of sick partner' (CSP). Although we used two different strains of mice and two
      different tumor types, the CSP mice presented, in relation to the CHP mice, an
      increased locomotion in the open field and plus maze apparatuses and no changes
      in the corticosterone serum levels before and after the immobilization-stress
      challenge. The Swiss CSP mice showed a reduced level and an increased turnover
      rate of hypothalamic noradrenaline (NE), as well as increased plasmatic levels of
      adrenaline and NE. Changes in the immune cell phenotype and activity were also
      observed in the Swiss and C57Bl/6 CSP mice. The study found that odor cues left
      by the Ehrlich tumor-injected Swiss mice are aversive and may therefore be
      responsible for the neuroimmune changes reported in the CSP mice. It is proposed
      that the final neural link between the neuroimmunological changes observed in the
      CSP mice involves psychogenic stress imposed by the housing condition and the
      activation of the brain catecholaminergic pathways and the sympathetic nervous
      systems. 

PMID- 24588826
TI  - Physiologic versus diabetogenic effects of interleukin-1: a question of weight.
AB  - Pleiotropic effects, great potency, and the capacity to induce its own production
      are distinguishing characteristics of IL-1. Among the multiple physiological
      effects of this cytokine, we emphasize here its role in supporting immune
      processes by stimulating most immune cells, and in re-setting glucose
      homeostasis. These aspects are complementary because stimulatory actions of IL-1
      may be due to its capacity to increase glucose uptake by immune cells in the
      periphery and to affect the control of glucose homeostasis at brain levels, so as
      to deviate this main fuel to immune cells during inflammatory and infectious
      diseases. Thus, IL-1 can contribute to maintain a lean phenotype, inhibit food
      intake, and exert hypoglycemic effects. However, these effects of IL-1 can be
      overridden particularly when it is overproduced ectopically in other tissues, as
      it occurs during the autoimmune process that destroys the pancreas and causes
      type 1 diabetes, or when obesity triggers its production in adipose tissue and
      influences the development of type 2 diabetes. During obesity, products of
      enlarged adipocytes, e.g. fatty acids, are sensed as danger signals by
      infiltrating immune cells and, together with hypoxia, results in an ectopic
      overproduction of IL-1 that is largely mediated by activation of the NLRP3
      caspase-1 inflammasome. Insulin and leptin resistance develops by mutual IL-1beta
      TNFalpha induction, and hyperglycemia causes ectopic production of IL-1 in the
      pancreas, which deregulates insulin production and favors the development of type
      2 diabetes. In conclusion, whether IL-1 exerts physiologic or pathologic effects
      depends on its amount and on the spatial and temporal pattern of its production.

PMID- 24588827
TI  - Host neuro- immuno-endocrine responses in periodontal disease.
AB  - Periodontitis is a chronic inflammatory complex disease caused by microorganisms.
      It may be influenced by diverse systemic disorders, environmental, genetic and
      socio-psychological factors with the ability to alter the balance of the host
      neuro-immunoendocrine responses. It is characterized by the progressive
      destruction of the tooth supporting apparatus leading to tooth loss, with
      possible impact on general health. Starting with a brief description of the
      periodontium, etiopathogenesis, repair processes and several physiological
      mechanisms and their disarray on periodontium response to bacterial challenge.
      Following, the negative effects of stress on the disease and some remarks on the
      recently discovered effects of oxytocin that modulate stress response and its
      role in individual coping mechanisms to stress. We also focus on the
      participation of components and functions of endocannabinoid system with anti
      inflammatory actions on gingiva. Finally, a discussion that may link between
      diabetes, cardiovascular diseases, stroke and metabolic syndrome associated with
      periodontal disease; all of them sharing a common denominator that is
      inflammation and oxidative stress.

PMID- 24588828
TI  - Neuroimmune aspects of Sjogren's syndrome: role of VIP/VPAC system in immune and
      salivary gland epithelial cell function.
AB  - Sjogren's syndrome (SS) is a chronic inflammatory disease characterized by
      salivary and lacrimal gland dysfunction although extraglandular manifestations
      are also found. Suitable study models and in vitro cell culture designs are used
      to approach SS pathogenic mechanisms. Cellular and molecular pathways involved in
      gland homeostasis loss and the autoimmune response are focused in the search of
      novel drug targets and biomarkers. Vasoactive intestinal peptide (VIP) has
      trophic, pro-secretory and immunomodulatory effects in several chronic and
      autoimmune disease models. Here we review evidence pointing to its role as an
      endogenous modulator of gland homeostasis at early stages of the disease.
      Particularly, mechanisms involving VIP/VPAC system in the course of salivary
      function impairment in the non obese diabetic (NOD) mouse model of Sjogren's
      syndrome are described. 

PMID- 24588830
TI  - Inflammation, infection and preterm birth.
AB  - Preterm birth is the leading cause of perinatal morbidity and mortality.
      Pathological processes that have been linked with preterm birth infection and /
      or intrauterine inflammation are most frequently found associated with their
      induction. Studies in animal models and human research showed prior infections to
      the induction of labor, the anteriority of infection over labor induction, and
      the existence of a subclinical latency phase between these two phenomena. The
      ascending route from the vagina and the cervix is preponderant but also
      microorganisms may access the amniotic cavity and the fetus by other pathways.
      During inflammation associated to infection, Prostaglandins are released
      simultaneously with Nitric oxide and their overproduction could be detrimental.
      Prostaglandins promote uterine contractions contributing to embryonic and fetal
      expulsion. Therefore aberrant activation of the inflammatory response may cause
      premature labor and this does not seem to depend on how the microoorganisms
      accessed the uterus. 

PMID- 24588831
TI  - Increase of oxidation and inflammation in nervous and immune systems with aging
      and anxiety.
AB  - According to the oxidation-inflammation theory of aging, chronic oxidative stress
      and inflammatory stress situations (with higher levels of oxidant and
      inflammatory compounds and lower antioxidant and anti-inflammatory defenses) are
      the basis of the agerelated impairment of organism functions, including those of
      the nervous and immune systems, as well as of the neuroimmune communication,
      which explains the altered homeostasis and the resulting increase of morbidity
      and mortality. Overproduction of oxidant compounds can induce an inflammatory
      response, since oxidants are inflammation effectors. Thus, oxidation and
      inflammation are interlinked processes and have many feedback loops. However, the
      nature of their potential interactions, mainly in the brain and immune cells, and
      their key involvement in aging remain unclear. Moreover, in the context of the
      neuroimmune communication, it has been described that an oxidative-inflammatory
      situation occurs in subjects with anxiety, and this situation contributes to an
      immunosenescence, alteration of survival responses and shorter life span. As an
      example of this, a model of premature aging in mice, in which animals show a poor
      response to stress and high levels of anxiety, an oxidative stress in their
      immune cells and tissues, as well as a premature immunosenescence and a shorter
      life expectancy, will be commented in the present review. This model supports the
      hypothesis that anxiety can be a situation of chronic oxidative stress and
      inflammation, especially in brain and immune cells, and this accelerates the rate
      of aging. 

PMID- 24588832
TI  - Chronobiology of the neuroimmunoendocrine system and aging.
AB  - The health maintenance depends on the preservation of the homeostatic systems,
      such as nervous, endocrine and immune system, and a proper communication between
      them. In this regard, the circadian system, which promotes a better physiological
      system functions and thus well being, could be considered part of that
      homeostatic complex, since the neuroimmunoendocrine system possesses circadian
      patterns in most variables, as well as circannual or seasonal variations. With
      aging, an impairment of the homeostatic systems occurs and an alteration of
      circadian system regulation has been demonstrated. In the immune system, several
      function parameters, which are good markers of health and of the rate of aging,
      change not only with age (immunosenescence) but also throughout the day and year.
      Indeed, with advancing age there is a modification of immune cell circadian
      function especially in lymphocytes. Moreover, immune functions at early afternoon
      correspond to more aged values than at morning, especially in mature subjects (60
      79 years of age). In addition, these mature men and women showed a significant
      impaired immune cell function, which is especially remarkable in the winter. It
      is noteworthy the role of immunomodulatory hormones, such as melatonin, in the
      regulation of biological rhythms and their involvement in the aging process.
      Furthermore, the evidence of a neuroimmune regulation of the circadian system and
      its disturbance with aging, highlights the importance of proinflammatory
      cytokines in this complex cross-talk. The biological rhythms disruption with age
      and some diseases (jet lag, cancer and seasonal affective disorder), could
      contribute increasing the immune system impairment and consequently the loss of
      health.

PMID- 24588829
TI  - Brain innate immunity in the regulation of neuroinflammation: therapeutic
      strategies by modulating CD200-CD200R interaction involve the cannabinoid system.
AB  - The central nervous system (CNS) innate immune response includes an arsenal of
      molecules and receptors expressed by professional phagocytes, glial cells and
      neurons that is involved in host defence and clearance of toxic and dangerous
      cell debris. However, any uncontrolled innate immune responses within the CNS are
      widely recognized as playing a major role in the development of autoimmune
      disorders and neurodegeneration, with multiple sclerosis (MS) Alzheimer's disease
      (AD) being primary examples. Hence, it is important to identify the key
      regulatory mechanisms involved in the control of CNS innate immunity and which
      could be harnessed to explore novel therapeutic avenues. Neuroimmune regulatory
      proteins (NIReg) such as CD95L, CD200, CD47, sialic acid, complement regulatory
      proteins (CD55, CD46, fH, C3a), HMGB1, may control the adverse immune responses
      in health and diseases. In the absence of these regulators, when neurons die by
      apoptosis, become infected or damaged, microglia and infiltrating immune cells
      are free to cause injury as well as an adverse inflammatory response in acute and
      chronic settings. We will herein provide new emphasis on the role of the pair
      CD200-CD200R in MS and its experimental models: experimental autoimmune
      encephalomyelitis (EAE) and Theiler's virus induced demyelinating disease (TMEV
      IDD). The interest of the cannabinoid system as inhibitor of inflammation prompt
      us to introduce our findings about the role of endocannabinoids (eCBs) in
      promoting CD200-CD200 receptor (CD200R) interaction and the benefits caused in
      TMEV-IDD. Finally, we also review the current data on CD200-CD200R interaction in
      AD, as well as, in the aging brain.

PMID- 24588833
TI  - The effect of time to treatment on outcome in very elderly thrombolysed stroke
      patients.
AB  - BACKGROUND: Intravenous thrombolysis is beneficial in, even very elderly, acute
      ischemic stroke patients. However, while the relation between treatment benefit
      and treatment delay (onset time to treatment) in patients younger than 80 years
      is well known, it is uncertain in the very elderly. AIMS: This analysis aims at
      examining this relationship in the elderly, and to provide a comparison with the
      derived relationship in younger patients as a check of validity. METHODS: We
      assessed the interaction between age, onset time to treatment, and thrombolysis
      exposure by analyzing the modified Rankin scale score distribution or mortality
      rate at 90 days, among patients registered in a trials archive. We established
      whether the effect of alteplase changes with onset time to treatment, by treating
      onset time to treatment as a continuum in a multivariate logistic regression
      model. RESULTS: Data were available for 3063 patients, of whom 2341 were
      thrombolysed. Five hundred ninety-seven patients were aged >80, of whom 352 were
      thrombolysed. Among patients aged >80, no significant interaction of outcome with
      onset time to treatment was observed (P = 0.4650), but the estimated slope of the
      decay in benefit with onset time to treatment was comparable with that
      established for younger patients. Analyzing the entire dataset, there was an
      interaction between onset time to treatment and alteplase treatment (P = 0.0159),
      but neither between age and onset time to treatment (P = 0.7098) nor between age
      and alteplase treatment (P = 0.0755). CONCLUSIONS: In this nonrandomized
      comparison, the relationship of benefit and safety with thrombolysis across onset
      time to treatment in very elderly stroke patients was comparable with that in
      their younger counterparts. Across the investigated time span of 3.5 h, we can
      safely treat with the same time window as we use for younger patients.

PMID- 24588834
TI  - Synthesis of the antiproliferative agent hippuristanol and its analogues from
      hydrocortisone via Hg(II)-catalyzed spiroketalization: structure-activity
      relationship.
AB  - An efficient synthesis of hippuristanol (1), a marine-derived highly potent
      antiproliferative steroidal natural product, and nine closely related analogues
      has been accomplished from the commercially available hydrocortisone utilizing
      Hg(II)-catalyzed spiroketalization of 3-alkyne-1,7-diol motif as a key strategy.
      This practical synthetic sequence furnished 1 in 11% overall yield from
      hydrocortisone in 15 linear steps. Modifications to the parent molecule 1
      encompassed changing the functional groups on rings A and E. Each analogue was
      screened for their effects on inhibition of cap-dependent translation, and the
      assay results were used to establish structure-activity relationships. These
      results suggest that the stereochemistry and all substituents of spiroketal
      portion (rings E and F) and C3-alpha and C11-beta hydroxyl functional groups on
      rings A and C, respectively, are critical for the inhibitory activity of natural
      product 1. 

PMID- 24588835
TI  - An efficient, practical, and enantioselective method for synthesis of
      homoallenylamides catalyzed by an aminoalcohol-derived, boron-based catalyst.
AB  - A practical catalytic method for enantioselective addition of an allene unit to
      aldimines is disclosed. Transformations are promoted by an in-situ-generated B
      based catalyst that is derived from a simple, robust, and readily accessible (in
      multigram quantities) chiral aminoalcohol. A range of aryl-, heteroaryl-, and
      alkyl-substituted homoallenylamides can be obtained in 66-91% yield and 84:16 to
      >99:1 enantiomeric ratio through reactions performed at ambient temperature and
      in the presence of 0.1-3.0 mol% of the chiral catalyst and a commercially
      available allenylboron reagent. The catalytic protocol does not require strict
      anhydrous conditions, can be performed on gram scale, and promotes highly
      selective addition of an allenyl unit (vs a propargyl group). The utility of the
      approach is demonstrated through development of succinct approaches to syntheses
      of anisomycin and epi-cytoxazone. 

PMID- 24588836
TI  - Editorial comment to Tadalafil 5 mg once-daily therapy for men with lower urinary
      tract symptoms suggestive of benign prostatic hyperplasia: results from a
      randomized, double-blind, placebo-controlled trial carried out in Japan and
      Korea.

PMID- 24588837
TI  - Obesity and health behaviours of British adults with self-reported intellectual
      impairments: cross sectional survey.
AB  - BACKGROUND: People with intellectual disability have significantly higher age
      adjusted rates of mortality and morbidity (including obesity) than their non
      disabled peers. They are also significantly less likely to be physically active.
      METHODS: Secondary analysis of de-identified cross-sectional data from the first
      two waves of Understanding Society, a new longitudinal study focusing on the life
      experiences of UK citizens. Interviews were undertaken with 50,994 individuals
      aged 16 and over in Wave 1 and 54,585 in Wave 2. Of these, 520 participants age
      16-49 (1.8% of the unweighted age-restricted sample) were identified at either
      Wave 1 or Wave 2 as having self-reported intellectual impairments. RESULTS:
      British adults with self-reported intellectual impairments have higher rates of
      obesity, inactivity, tobacco and alcohol use and poorer nutrition than their non
      disabled peers. Adjusting risk estimates for between group differences in age,
      gender and exposure to material hardship indicated that a significant proportion
      of their increased risk of obesity, tobacco use and poorer nutrition may be
      attributable to their poorer living conditions (rather than their self-reported
      intellectual impairments per se). CONCLUSIONS: People with intellectual
      disabilities should begin to be regarded as a 'vulnerable' group in the context
      of public health policy and practice.

PMID- 24588838
TI  - Choroidal thickness in eyes with posterior recurrence of Vogt-Koyanagi-Harada
      disease after high-dose steroid therapy.

PMID- 24588839
TI  - "Blurred lines?" Sexual aggression and barroom culture.
AB  - BACKGROUND: Meeting potential sexual/romantic partners for mutual pleasure is one
      of the main reasons young adults go to bars. However, not all sexual contacts are
      positive and consensual, and aggression related to sexual advances is a common
      experience. Sometimes such aggression is related to misperceptions in making and
      receiving sexual advances while other times aggression reflects intentional
      harassment or other sexually aggressive acts. This study uses objective
      observational research to assess quantitatively gender of initiators and targets
      and the extent that sexual aggression involves intentional aggression by the
      initiator, the nature of responses by targets, and the role of third parties and
      intoxication. METHODS: We analyzed 258 aggressive incidents involving sexual
      advances observed as part of a larger study on aggression in large capacity bars
      and clubs, using variables collected as part of the original research (gender,
      intoxication, intent) and variables coded from narrative descriptions
      (invasiveness, persistence, targets' responses, role of third parties).
      Hierarchical linear modeling analyses were used to account for nesting of
      incidents in evening and bars. RESULTS: Ninety percent of incidents involved male
      initiators and female targets, with almost all incidents involving intentional or
      probably intentional aggression. Targets mostly responded nonaggressively,
      usually using evasion. Staff rarely intervened; patron third parties intervened
      in 21% of incidents, usually to help the target but sometimes to encourage the
      initiator. initiators' level of invasiveness was related to intoxication of the
      targets, but not their own intoxication, suggesting intoxicated women were being
      targeted. CONCLUSIONS: Sexual aggression is a major problem in bars often
      reflecting intentional sexual invasiveness and unwanted persistence rather than
      misperceptions in sexual advances. Prevention needs to focus on addressing
      masculinity norms of male patrons and staff who support sexual aggression and
      better management of the highly sexualized and sexist environments of most bars.

PMID- 24588840
TI  - Full-field synchrotron tomography of nongraphitic foam and laminate anodes for
      lithium-ion batteries.
AB  - Nondestructive methods that allow researchers to gather high-resolution
      quantitative information on a material's physical properties from inside a
      working device are increasingly in demand from the scientific community.
      Synchrotron-based microcomputed X-ray tomography, which enables the fast, full
      field interrogation of materials in functional, real-world environments, was used
      to observe the physical changes of next-generation lithium-ion battery anode
      materials and architectures. High capacity, nongraphitic anodes were chosen for
      study because they represent the future direction of the field and one of their
      recognized limitations is their large volume expansion and contraction upon
      cycling, which is responsible for their generally poor electrochemical
      performance. In this work, Cu6Sn5 coated on a three-dimensional copper foam was
      used to model a high power electrode while laminated silicon particles were used
      to model a high energy electrode. The electrodes were illuminated in situ and ex
      situ, respectively, at Sector 2-BM of the Advanced Photon Source. The changes in
      electrode porosity and surface area were measured and show large differences
      based on the electrode architecture. This work is one of the first reports of
      full-field synchrotron tomography on high-capacity battery materials under
      operating conditions. 

PMID- 24588841
TI  - Child death in the United States: productivity and the economic burden of
      parental grief.
AB  - This article examines the economic consequences associated with the death of a
      child. The economic costs (funeral and medical expenses and productivity losses)
      of child death 6 months following the death were estimated based on 213 parents
      who had experienced the death of a child (usually unexpectedly and predominantly
      mothers). Findings suggest that productivity losses associated with child death
      comprise most of the costs and that the economic effects are substantial. Costs
      associated with on-the-job productivity losses ("presenteeism") outweigh the
      costs associated with absenteeism. To date, no research has empirically measured
      both absenteeism and presenteeism following bereavement. 

PMID- 24588842
TI  - Comparison of procedural and long-term outcomes between transradial and
      transfemoral approach in one-stage intervention for triple vessel coronary artery
      disease.
AB  - OBJECTIVES: The aim of the present study was to evaluate the safety, feasibility,
      procedural, and long-term outcomes by the transradial (TR) approach as compared
      to transfemoral (TF) approach in patients with triple vessel coronary artery
      disease undergoing one-stage percutaneous coronary intervention. BACKGROUND: The
      feasibility, safety, and efficacy between the TR and TF approach for coronary
      interventional treatment have been compared in some complex situations including
      AMI and unprotected left main disease. However, in terms of triple vessel disease
      (3VD) intervention, there has been no comparison regarding procedural and long
      term outcomes between the TR and TF approach. METHODS: A total of 4,974
      consecutive patients (TR n = 3,856, TF n = 1,118), who were diagnosed with 3VD
      without LM disease and underwent one-stage percutaneous revascularization, were
      enrolled in the study. Procedural results and clinical outcomes were obtained
      through database and follow-up. We used the propensity score matching method and
      obtained 930 pairs of patients with comparable baseline data in order to compare
      the procedural and long-term outcome between TR and TF groups. In the study
      cohort, risk reduction of all the clinical outcomes were evaluated with Cox's
      proportional-hazards models. Cumulative incidences concerning safety and efficacy
      of the cohort were estimated by the Kaplan-Meier method and a comparison was made
      utilizing the log-rank test. RESULTS: After propensity score matching, the
      baseline clinical and angiographic characteristics were similar between the 2
      groups. Regarding procedural results, no significant differences were observed
      between the 2 groups, with the exception of a decreased hospital stay (TR 7.49 +/
      4.46 days vs. TF 8.63 +/- 6.23 days, P < 0.0001) and fewer bleedings (TR 1.0%
      vs. TF 2.9, P = 0.003) in the TRI group. After an average 21-month follow-up, the
      all-cause mortality (TR 1.7% vs. TF 4.2%, P = 0.0014; HR 0.44, 0.25-0.79) was
      significantly lower with TRI patients. Other clinical outcomes were comparable
      between the 2 groups. CONCLUSIONS: As compared to TFI, TRI for 3VD intervention
      is feasible, safe, and associated with similar procedural success, shorter
      hospitalization, reduced bleeding, lower incidence of death, and comparable long
      term efficacy.

PMID- 24588843
TI  - The collagen cross-linking enzyme lysyl oxidase is associated with the healing of
      human atherosclerotic lesions.
AB  - BACKGROUND: Acute clinical complications of atherosclerosis such as myocardial
      infarction (MI) and ischaemic stroke are usually caused by thrombus formation on
      the ruptured plaque surface. Collagen, the main structural protein of the fibrous
      cap, provides mechanical strength to the atherosclerotic plaque. The integrity of
      the fibrous cap depends on collagen fibre cross-linking, a process controlled by
      the enzyme lysyl oxidase (LOX). METHODS AND RESULTS: We studied atherosclerotic
      plaques from human carotid endarterectomies. LOX was strongly expressed in
      atherosclerotic lesions and detected in the regions with ongoing fibrogenesis.
      Higher LOX levels were associated with a more stable phenotype of the plaque. In
      the studied population, LOX mRNA levels in carotid plaques predicted the risk for
      future MI. Within the lesion, LOX mRNA levels correlated positively with levels
      of osteoprotegerin (OPG) and negatively with markers of immune activation. The
      amount of LOX-mediated collagen cross-links in plaques correlated positively also
      with serum levels of OPG. CONCLUSIONS: Lysyl oxidase may contribute to the
      healing of atherosclerotic lesions and to the prevention of its lethal
      complications. Mediators of inflammation may control LOX expression in plaques
      and hence plaque stability.

PMID- 24588844
TI  - Development of navigational working memory: evidence from 6- to 10-year-old
      children.
AB  - The ability to learn complex environments may require the contribution of
      different types of working memory. Therefore, we investigated the development of
      different types of working memory (navigational, reaching, and verbal) in 129
      typically developing children. We aimed to determine whether navigational working
      memory develops at the same rate as other types of working memory and whether the
      gender differences reported in adults are already present during development. We
      found that navigational working memory is less developed than both verbal and
      reaching working memory and that gender predicts performance only for
      navigational working memory. Our results are in line with reports that children
      made significantly more errors in far space than adults, showing that near space
      representation develops before far space representation. 

PMID- 24588845
TI  - Impact of comorbidity on health-related quality of life after prostate cancer
      treatment: combined analysis of two prospective cohort studies.
AB  - OBJECTIVE: To improve and individualise estimates of treatment outcomes for men
      diagnosed with prostate cancer, we examined the impact of baseline comorbidity on
      health-related quality of life (HRQL) outcomes in an analysis of two pooled,
      prospective cohort studies. PATIENTS AND METHODS: We studied 697 patients from
      three academic hospitals who received radical prostatectomy (RP), external beam
      radiation therapy (EBRT), or brachytherapy (BT). Measures of patient-reported
      bowel, urinary, and sexual symptoms along with physical and mental health were
      prospectively collected before treatment and 3, 12, 24, and 36 months after
      treatment. We assessed baseline comorbidity by the validated Index of Co-Existent
      Disease (ICED), abstracted from medical records. Regression mixed-models were
      built for each treatment group and HRQL outcome controlling for baseline age,
      education, marital status, risk group and patient-reported general health.
      RESULTS: About 71% of patients had one or more comorbid conditions at baseline.
      After adjusting for covariates, we found baseline comorbidity was independently
      associated with poorer sexual function after BT (P = 0.04) and RP (P = 0.03) but
      not EBRT (P = 0.35). Physical health was significantly worse for men receiving BT
      with more comorbidities (P = 0.02). Baseline comorbid conditions were not
      associated with urinary incontinence or bowel functioning. CONCLUSIONS:
      Comorbidity at baseline is significantly associated with poorer sexual function
      after prostate BT or RP. This information may help patients and their physicians
      anticipate outcomes after surgical and radiation treatments.

PMID- 24588846
TI  - Efficacy and safety of ondansetron in preventing postanesthesia shivering: a meta
      analysis of randomized controlled trials.
AB  - BACKGROUND: Shivering is a very common complication in the postanesthesia period.
      Increasing studies have reported ondansetron may be effective in prevention of
      postanesthesia shivering (PAS). However, the results remained controversial;
      hence we conducted a meta-analysis of randomized controlled trials to evaluate
      the efficacy and safety of ondansetron on the prevention of postanesthesia
      shivering. METHODS: PubMed and Embase databases were searched to identify the
      eligible randomized controlled trials assessing the effect of ondansetron on the
      prevention of PAS. Results were expressed as risk ratios (RRs) with accompanying
      95% confidence intervals (CIs). The meta-analysis was performed with fixed-effect
      model or random-effect model according to the heterogeneity. RESULTS: Six trials
      including 533 subjects were included. Compared with placebo, ondansetron was
      associated with a significant reduction of PAS (RR 0.43, 95% CI, 0.27-0.70),
      without an increased risk of bradycardia (RR 0.37, 95% CI, 0.12-1.15). Compared
      with meperidine, no difference was observed in the incidence of PAS (RR 0.68, 95%
      CI, 0.39-1.19) and bradycardia (RR 2.0, 95% CI, 0.38-10.64). CONCLUSIONS:
      Ondansetron has a preventive effect on PAS without a paralleled side effect of
      bradycardia.

PMID- 24588848
TI  - Characteristics of residential areas and transportational walking among frail and
      non-frail Dutch elderly: does the size of the area matter?
AB  - BACKGROUND: A residential area supportive for walking may facilitate elderly to
      live longer independently. However, current evidence on area characteristics
      potentially important for walking among older persons is mixed. This study
      hypothesized that the importance of area characteristics for transportational
      walking depends on the size of the area characteristics measured, and older
      person's frailty level. METHODS: The study population consisted of 408 Dutch
      community-dwelling persons aged 65 years and older participating in the Elderly
      And their Neighborhood (ELANE) study in 2011-2012. Characteristics (aesthetics,
      functional features, safety, and destinations) of areas surrounding participants'
      residences ranging from a buffer of 400 meters up to 1600 meters (based on
      walking path networks) were linked with self-reported transportational walking
      using linear regression analyses. In addition, interaction effects between
      frailty level and area characteristics were tested. RESULTS: An increase in
      functional features (e.g. presence of sidewalks and benches) within a 400 meter
      buffer, in aesthetics (e.g. absence of litter and graffiti) within 800 and 1200
      meter buffers, and an increase of one destination per buffer of 400 and 800
      meters were associated with more transportational walking, up to 2.89 minutes per
      two weeks (CI 1.07-7.32; p < 0.05). No differences were found between frail and
      non-frail elderly. CONCLUSIONS: Better functional and aesthetic features, and
      more destinations in the residential area of community-dwelling older persons
      were associated with more transportational walking. The importance of area
      characteristics for transportational walking differs by area size, but not by
      frailty level. Neighbourhood improvements may increase transportational walking
      among older persons, thereby contributing to living longer independently.

PMID- 24588849
TI  - Increased EMRSA-15 health-care worker colonization demonstrated in retrospective
      review of EMRSA hospital outbreaks.
AB  - BACKGROUND: Health care worker (HCW) colonization with methicillin resistant
      Staphylococcus aureus (MRSA) is a documented cause of hospital outbreaks and
      contributes to ongoing transmission. At Royal Perth Hospital (RPH) it had been
      anecdotally noted that the increasing prevalence of EMRSA-15 appeared to be
      associated with increased HCW colonization compared with Aus2/3-EMRSA. Hence we
      compared HCW colonization rates during outbreaks of EMRSA-15 and Aus2/3-EMRSA at
      a single institution. METHODS: We performed a retrospective review of EMRSA-15
      and Aus2/3-EMRSA outbreaks from 2000-2009 at RPH, a quaternary hospital in
      Western Australia. Outbreak files were reviewed and relevant data extracted.
      RESULTS: Ten EMRSA-15 outbreaks were compared with seven Aus2/3 outbreaks. The
      number of patients colonized was similar between EMRSA-15 and Aus2/3-EMRSA
      outbreaks (median 7 [range 3-20] and 11 [5-26], respectively; P = 0.07) but the
      number of HCWs colonized was significantly higher in EMRSA-15 outbreaks compared
      to Aus2/3-EMRSA outbreaks (median 4 [range 0-15] and 2 [1-3], respectively; P =
      0.013). The percentage of HCWs colonized was also higher in EMRSA-15 outbreaks
      versus Aus2/3-EMRSA outbreaks (median 3.4% [range 0-5.5%] and 0.81% [0.56-2.2%],
      respectively; P = 0.013). CONCLUSIONS: This study demonstrates a higher level of
      HCW colonization during EMRSA-15 outbreaks compared with Aus2/3-EMRSA outbreaks.
      This finding suggests that MRSA vary in their ability to colonize HCWs and
      contribute to outbreaks. MRSA type should be determined during outbreaks and
      future research should investigate the mechanisms by which EMRSA-15 contributes
      to increased HCW colonization.

PMID- 24588850
TI  - Molecular characterization of the citrate transporter gene TaMATE1 and expression
      analysis of upstream genes involved in organic acid transport under Al stress in
      bread wheat (Triticum aestivum).
AB  - In bread wheat, besides malate, the importance of citrate efflux for Al tolerance
      has also been reported. For better understanding the Al tolerance mechanism in
      bread wheat, here, we performed both a molecular characterization of the citrate
      transporter gene TaMATE1 and an investigation on the upstream variations in
      citrate and malate transporter genes. TaMATE1 belong to multidrug transporter
      protein family, which are located on the long arm of homoeologous group 4
      chromosomes (TaMATE1-4A, TaMATE1-4B TaMATE1-4D). TaMATE1 homoeologues transcript
      expression study exhibited the preponderance of homoeologue TaMATE1-4B followed
      by TaMATE1-4D whereas homoeologue TaMATE1-4A seemed to be silenced. TaMATE1,
      particularly homoeologue TaMATE1-4B and TaALMT1 transcripts were much more
      expressed in the root apices than in shoots of Al tolerant genotype Barbela
      7/72/92 under both control and Al stress conditions. In addition, in both tissues
      of Barbela 7/72/92, higher basal levels of these gene transcripts were observed
      than in Anahuac (Al sensitive). Noticeably, the presence of a transposon in the
      upstream of TaMATE1-4B in Barbela 7/72/92 seems to be responsible for its higher
      transcript expression where it may confer citrate efflux. Thus, promoter
      variations (transposon in TaMATE1-4B upstream and type VI promoter in TaALMT1)
      associated with higher basal transcript expression of TaMATE1-4B and TaALMT1
      clearly show how different mechanisms for Al tolerance operate simultaneously in
      a single genotype. In conclusion, our results demonstrate that Barbela 7/72/92
      has favorable alleles for these organic acids transporter genes which could be
      utilized through genomic assisted selection to develop improved cultivars for
      acidic soils. 

PMID- 24588851
TI  - Pills, policies, and predicaments: the unintended consequences of a health care
      system's policy toward opioids.

PMID- 24588852
TI  - Prescription opioids and benzodiazepines: moving beyond "just say no".

PMID- 24588853
TI  - Disease-outcome trees, EQ-5D scores, and estimated annual losses of quality
      adjusted life years (QALYs) for 14 foodborne pathogens in the United States.
AB  - Measures of disease burden such as quality-adjusted life years (QALYs) are
      increasingly important to risk-based food safety policy. They provide a means of
      comparing relative risk from diverse health outcomes. We present detailed disease
      outcome trees and EQ-5D scoring for 14 major foodborne pathogens representing
      over 95% of foodborne illnesses, hospitalizations, and deaths due to specified
      agents in the United States (Campylobacter spp., Clostridium perfringens,
      Cryptosporidium parvum, Cyclospora cayetanensis, Escherichia coli O157:H7, Shiga
      toxin-producing E. coli non-O157, Listeria monocytogenes, nontyphoidal Salmonella
      enterica, Shigella, Toxoplasma gondii, Vibrio vulnificus, Vibrio parahaemolyticus
      and other noncholera Vibrio, and Yersinia enterocolitica). We estimate over 5800
      QALYs lost per 1000 cases of L. monocytogenes and V. vulnificus, compared to 125
      QALYs lost per 1000 cases of T. gondii, 26 for E. coli O157:H7, 16 for Salmonella
      and Campylobacter, and 14 for Y. enterocolitica. The remaining 7 pathogens are
      estimated to cause less than 5 QALYs lost per 1000 cases. In total, these 14
      pathogens cause over 61,000 in QALY loss annually, with more than 90% due solely
      to acute infection being responsible for 65% of total QALY loss, with premature
      mortality and morbidity due to chronic and congenital illness responsible for
      another 28%. These estimates of the burden of chronic sequelae are likely
      conservative; additional epidemiological research is needed to support more
      accurate burden estimates. This study shows the value of using integrated metrics
      for comparing disease burden, and the need to consider chronic and congenital
      illness when prioritizing foodborne pathogens.

PMID- 24588854
TI  - Human choriogonadotropin and epoetin alfa in acute ischemic stroke patients
      (REGENESIS-LED trial).
AB  - INTRODUCTION: Preclinical studies suggest that growth factors in the early days
      after stroke improve final outcome. A prior study found three doses of human
      choriogonadotropin alfa followed by three doses of erythropoietin to be safe
      after stroke in humans. A proof of concept trial (REGENESIS) was initiated but
      placed on regulatory hold during review of an erythropoietin neuroprotective
      trial. Due to financial constraints, the trial was largely moved to India, using
      lower erythropoietin doses, as the REGENESIS-LED trial. METHODS: Entry criteria
      included National Institutes of Health Stroke Scale 8-20, supratentorial ischemic
      stroke, and 24-48 h poststroke at start of therapy. Patients were randomized to
      three QOD doses of subcutaneous human choriogonadotropin alfa followed by three
      QD doses of intravenous erythropoietin (three escalating dose cohorts, 4000
      20,000 IU/dose) vs. placebo. Primary outcomes were safety and neurological
      recovery. RESULTS: The study was halted early by the sponsor after 96 enrollees.
      There was no significant difference across treatment groups in the proportion of
      patients experiencing death, serious adverse events, or any adverse event. There
      was no significant difference in National Institutes of Health Stroke Scale score
      change from baseline to Day 90 between placebo and active treatment, whether
      active cohorts were analyzed together or separately, and no exploratory secondary
      measure of neurological recovery showed a significant difference between groups.
      DISCUSSION: Administration of human choriogonadotropin alfa followed by
      erythropoietin is safe after a new ischemic stroke. At the doses studied, placebo
      and active groups did not differ significantly in neurological recovery. Study
      limitations, such as the use of multiple assessors, differences in rehabilitation
      care, and being underpowered to show efficacy, are discussed.

PMID- 24588855
TI  - Genomic variation in macrophage-cultured European porcine reproductive and
      respiratory syndrome virus Olot/91 revealed using ultra-deep next generation
      sequencing.
AB  - BACKGROUND: Porcine Reproductive and Respiratory Syndrome (PRRS) is a disease of
      major economic impact worldwide. The etiologic agent of this disease is the PRRS
      virus (PRRSV). Increasing evidence suggest that microevolution within a
      coexisting quasispecies population can give rise to high sequence heterogeneity
      in PRRSV. FINDINGS: We developed a pipeline based on the ultra-deep next
      generation sequencing approach to first construct the complete genome of a
      European PRRSV, strain Olot/9, cultured on macrophages and then capture the rare
      variants representative of the mixed quasispecies population. Olot/91 differs
      from the reference Lelystad strain by about 5% and a total of 88 variants, with
      frequencies as low as 1%, were detected in the mixed population. These variants
      included 16 non-synonymous variants concentrated in the genes encoding structural
      and nonstructural proteins; including Glycoprotein 2a and 5. CONCLUSION: Using an
      ultra-deep sequencing methodology, the complete genome of Olot/91 was constructed
      without any prior knowledge of the sequence. Rare variants that constitute minor
      fractions of the heterogeneous PRRSV population could successfully be detected to
      allow further exploration of microevolutionary events.

PMID- 24588856
TI  - Seroprevalence and genotype of Chlamydia in pet parrots in China.
AB  - Parrots are one of the most popular pet birds in China, and can harbour Chlamydia
      which has significance for human and animal health. We investigated, by indirect
      haemagglutination assay, the seroprevalence of Chlamydia infection in four
      species of parrots, namely budgerigars (Melopsittacus undulatus), lovebirds
      (Agapornis sp.), cockatiels (Nymphicus hollandicus) and Alexandrine parakeets
      (Psittacula eupatria) that were collected from Weifang and Beijing cities, North
      China and explored the association between potential risk factors and chlamydial
      seropositivity. We further determined the genotype of Chlamydia in 21 fresh
      faecal samples based on the ompA sequence by reconstruction of phylogenetic
      relationships. Of the 311 parrots examined, 35.37% (95% confidence interval 30.06
      40.68) were seropositive, and species, gender, age, season and geographical
      location were identified as risk factors. Two PCR-positive samples represented
      Chlamydia psittaci genotype A. The occurrence of C. psittaci genotype A in the
      droppings of two pet parrots in China suggests potential environmental
      contamination with Chlamydiaceae and may raise a public health concern.

PMID- 24588858
TI  - Good syndrome and lichen planus: case and review.

PMID- 24588857
TI  - Comparing factor, class, and mixture models of cannabis initiation and DSM
      cannabis use disorder criteria, including craving, in the Brisbane longitudinal
      twin study.
AB  - Accumulating evidence suggests that the Diagnostic and Statistical Manual of
      Mental Disorders (DSM) diagnostic criteria for cannabis abuse and dependence are
      best represented by a single underlying factor. However, it remains possible that
      models with additional factors, or latent class models or hybrid models, may
      better explain the data. Using structured interviews, 626 adult male and female
      twins provided complete data on symptoms of cannabis abuse and dependence, plus a
      craving criterion. We compared latent factor analysis, latent class analysis, and
      factor mixture modeling using normal theory marginal maximum likelihood for
      ordinal data. Our aim was to derive a parsimonious, best-fitting cannabis use
      disorder (CUD) phenotype based on DSM-IV criteria and determine whether DSM-5
      craving loads onto a general factor. When compared with latent class and mixture
      models, factor models provided a better fit to the data. When conditioned on
      initiation and cannabis use, the association between criteria for abuse,
      dependence, withdrawal, and craving were best explained by two correlated latent
      factors for males and females: a general risk factor to CUD and a factor
      capturing the symptoms of social and occupational impairment as a consequence of
      frequent use. Secondary analyses revealed a modest increase in the prevalence of
      DSM-5 CUD compared with DSM-IV cannabis abuse or dependence. It is concluded
      that, in addition to a general factor with loadings on cannabis use and symptoms
      of abuse, dependence, withdrawal, and craving, a second clinically relevant
      factor defined by features of social and occupational impairment was also found
      for frequent cannabis use. 

PMID- 24588859
TI  - International alcohol control study: pricing data and hours of purchase predict
      heavier drinking.
AB  - BACKGROUND: This study reports findings from the International Alcohol Control
      (IAC) study that assesses the impact of alcohol control policy on consumption and
      policy-related behaviors. Modeled on the International Tobacco Control study that
      uses longitudinal surveys with comparison between countries, the baseline survey
      was carried out in New Zealand. This study reports analysis of the purchasing
      behavior respondents report separately for on- and off-premise outlets, providing
      validation data for both alcohol consumption and reported prices. METHODS: New
      Zealand is a high-income country with an adult per capita alcohol consumption (as
      of 2011) of 9.5 l. The survey was carried out among a nationally representative
      sample of drinkers. Interview data on place and time of purchase, amounts
      purchased, price paid, and consumption (beverage and location specific) was
      collected. Relationships between policy relevant variables and consumption were
      modeled taking into account demographic variables. Validation was provided by
      government data on alcohol available for consumption, aggregate expenditure and
      prices from the Consumer Price Index. RESULTS: Drinkers paying low prices at on-
      or off-licensed premises had higher odds of consuming 6+ drinks on a typical
      occasion, as did drinkers purchasing alcohol at later times. Regarding frequency,
      drinkers purchasing at later times were more likely to be daily drinkers. Lower
      price in off licenses but not on licenses predicted daily drinking. The data
      collected accounted for approximately 96% of alcohol available for consumption
      and the prices accounted for 98% of aggregate expenditure. CONCLUSIONS: Valid
      survey data were collected to give an accurate picture of alcohol consumption and
      prices paid by drinkers. Heavy drinkers were more likely to buy cheaper alcohol
      and purchase at later times; 2 policy issues under discussion in many settings.
      This analysis suggests the IAC study that has the potential to provide data to
      contribute to the debate on appropriate policy responses to reduce alcohol
      related harm.

PMID- 24588860
TI  - Efficacy of MRI in primary care for patients with knee complaints due to trauma:
      protocol of a randomised controlled non-inferiority trial (TACKLE trial).
AB  - BACKGROUND: Patients with traumatic knee complaints regularly consult their
      general practitioner (GP). MRI might be a valuable diagnostic tool to assist GPs
      in making appropriate treatment decisions and reducing costs. Therefore, this
      study will assess the cost-effectiveness of referral to MRI by GPs compared with
      usual care, in patients with persistent traumatic knee complaints. DESIGN AND
      METHODS: This is a multi-centre, open-labelled randomised controlled non
      inferiority trial in combination with a concurrent observational cohort study.
      Eligible patients (aged 18-45 years) have knee complaints due to trauma (or
      sudden onset) occurring in the preceding 6 months and consulting their GP.
      Participants are randomised to: 1) an MRI group, i.e. GP referral to MRI, or 2) a
      usual care group, i.e. no MRI. Primary outcomes are knee-related daily function,
      medical costs (healthcare use and productivity loss), and quality of life.
      Secondary outcomes are disability due to knee complaints, severity of knee pain,
      and patients' perceived recovery and satisfaction. Outcomes are measured at
      baseline and at 1.5, 3, 6, 9 and 12 months follow-up. Also collected are data on
      patient demographics, GPs' initial working diagnosis, GPs' preferred management
      at baseline, and MRI findings. DISCUSSION: In the Netherlands, the additional
      diagnostic value and cost-effectiveness of direct access to knee MRI for patients
      presenting with traumatic knee complaints in general practice is unknown.
      Although GPs increasingly refer patients to MRI, the Dutch clinical guideline
      'Traumatic knee complaints' for GPs does not recommend referral to MRI, mainly
      because the cost-effectiveness is still unknown. TRIAL REGISTRATION: Dutch Trial
      Registration: NTR3689.

PMID- 24588862
TI  - Mast cell migration to airway smooth muscle in asthma. Can we Gro(w) something to
      block the attraction?

PMID- 24588863
TI  - Immune mechanisms of SCIT and SLIT: facing possible differences?

PMID- 24588864
TI  - Allergy to illicit drugs and narcotics.
AB  - Despite their frequent use, allergy to illicit drugs and narcotics is rarely
      reported in literature. We present a review of the different classes of drugs of
      abuse that might be involved in allergies: central nervous system (CNS)
      depressants (such as cannabis, opioids and kava), CNS stimulants (cocaine,
      amphetamines, khat and ephedra) and hallucinogens such as ketamine and nutmeg.
      Diagnosis of drug and narcotic allergy generally relies upon careful history
      taking, complemented with skin testing eventually along with quantification of
      sIgE. However, for various reasons, correct diagnosis of most of these drug
      allergies is not straightforward. For example, the native plant material applied
      for skin testing and sIgE antibody tests might harbour irrelevant IgE-binding
      structures that hamper correct diagnosis. Diagnosis might also be hampered due to
      uncertainties associated with the non-specific histamine releasing
      characteristics of some compounds and absence of validated sIgE tests. Whether
      the introduction of standardized allergen components and more functional tests,
      that is, basophil activation and degranulation assays, might be helpful to an
      improved diagnosis needs to be established. It is anticipated that due to the
      rare character of these allergies further validation is although necessary. 

PMID- 24588865
TI  - CXCL1 is a negative regulator of mast cell chemotaxis to airway smooth muscle
      cell products in vitro.
AB  - BACKGROUND: Activated mast cells (MC) numbers on airway smooth muscle (ASM) are
      increased in eosinophilic asthma. In vitro, asthmatic cytokine-stimulated ASM
      cell-conditioned medium (CM) induces more MC chemotaxis than CM from nonasthmatic
      ASM cells. Intriguingly the nonasthmatic ASM CM inhibits MC chemotaxis to the
      asthmatic ASM CM. However, the inhibitory factor(s) in the nonasthmatic ASM CM is
      still to be identified. OBJECTIVE: To identify the factor(s) released by
      nonasthmatic ASM cells that inhibits MC chemotaxis. METHODS: Confluent, serum
      starved ASM cells from donors with and without asthma were stimulated with IL
      1beta and T-helper (Th)1 (TNFalpha and IFNgamma) or Th2 (IL-4, IL-13) cytokines,
      or left unstimulated. CM samples were collected after 24 h, and a potential
      inhibitory factor identified using cytokine protein arrays. Its production was
      assessed using ELISA and RT-PCR and inhibitory role investigated in MC chemotaxis
      and Ca(2+) mobilization assays. RESULTS: Only CXCL1 was produced in greater
      amounts by nonasthmatic than asthmatic ASM cells following Th1 and Th2 cytokine
      stimulation. CXCL1 mRNA expression was also increased. Exogenous rh-CXCL1
      significantly inhibited MC intracellular Ca(2+) mobilization and chemotaxis to
      either CXCL10, CXCL8 or CM collected from asthmatic ASM cells following Th1 or
      Th2 cytokine stimulation. Neutralizing CXCL1 in nonasthmatic ASM CM or blocking
      its receptor significantly promoted MC chemotaxis. CONCLUSIONS: CXCL1 was a major
      factor regulating MC chemotaxis in vitro. Its differential release by ASM cells
      may explain the differences observed in MC localization to the ASM of people with
      and without asthma. CLINICAL RELEVANCE: CXCL1 inhibition of MC recruitment to the
      ASM may lead to new targets to limit asthma pathophysiology.

PMID- 24588866
TI  - Is the use of NMBA dissuaded in individuals who display positive sIgE to QAS?

PMID- 24588867
TI  - Reply to J. Leysen et al.

PMID- 24588869
TI  - Role of the histone H3 lysine 9 methyltransferase Suv39 h1 in maintaining
      Epsteinn-Barr virus latency in B95-8 cells.
AB  - The ability of Epstein-Barr Virus (EBV) to establish latent infection is
      associated with infectious mononucleosis and a number of malignancies. In EBV,
      the product of the BZLF1 gene (ZEBRA) acts as a master regulator of the
      transition from latency to the lytic replication cycle in latently infected
      cells. EBV latency is primarily maintained by hypoacetylation of histone proteins
      in the BZLF1 promoter by histone deacetylases. Although histone methylation is
      involved in the organization of chromatin domains and has a central epigenetic
      role in gene expression, its role in maintaining EBV latency is not well
      understood. Here we present evidence that the histone H3 lysine 9 (H3K9)
      methyltransferase suppressor of variegation 3-9 homolog 1 (Suv39 h1)
      transcriptionally represses BZLF1 in B95-8 cells by promoting repressive
      trimethylation at H3K9 (H3K9me3). Suv39 h1 significantly inhibited basal
      expression and ZEBRA-induced BZLF1 gene expression in B95-8 B cells. However,
      mutant Suv39 h1 lacks the SET domain responsible for catalytic activity of
      histone methyl transferase and thus had no such effect. BZLF1 transcription was
      augmented when Suv39 h1 expression was knocked down by siRNA in B95-8 cells, but
      not in Akata or Raji cells. In addition, treatment with a specific Suv39 h1
      inhibitor, chaetocin, significantly enhanced BZLF1 transcription. Furthermore,
      chromatin immunoprecipitation assays revealed the presence of Suv39 h1 and
      H3K9me3 on nucleosome histones near the BZLF1 promoter. Taken together, these
      results suggest that Suv39 h1-H3K9me3 epigenetic repression is involved in BZLF1
      transcriptional silencing, providing a molecular basis for understanding the
      mechanism by which EBV latency is maintained.

PMID- 24588870
TI  - Sputum myeloperoxidase in chronic obstructive pulmonary disease.
AB  - BACKGROUND: Airway inflammation, especially neutrophilic airway inflammation, is
      a cardinal pathophysiologic feature in chronic obstructive pulmonary disease
      (COPD) patients. The ideal biomarkers characterizing the inflammation might have
      important potential clinical applications in disease assessment and therapeutic
      intervention. Sputum myeloperoxidase (MPO) is recognized as a marker of
      neutrophil activity. The purpose of this meta-analysis is to determine whether
      sputum MPO levels could reflect disease status or be regulated by regular
      medications for COPD. METHODS: Studies were identified by searching PubMed,
      Embase, the Cochrane Database, CINAHL and http://www.controlled-trials.com for
      relevant reports published before September 2012. Observational studies comparing
      sputum MPO in COPD patients and healthy subjects or asthmatics, or within the
      COPD group, and studies comparing sputum MPO before and after treatment were all
      included. Data were independently extracted by two investigators and analyzed
      using STATA 10.0 software. RESULTS: A total of 24 studies were included in the
      meta-analysis. Sputum MPO levels were increased in stable COPD patients when
      compared with normal controls, and this increase was especially pronounced during
      exacerbations as compared with MPO levels during the stable state. Theophylline
      treatment was able to reduce MPO levels in COPD patients, while glucocorticoid
      treatment failed to achieve the same result. CONCLUSION: Sputum MPO might be a
      promising biomarker for guiding COPD management; however, further investigations
      are needed to confirm this.

PMID- 24588872
TI  - Ex-smokers are happier than current smokers among Chinese adults in Hong Kong.
AB  - AIM: To investigate the cross-sectional association between smoking and happiness
      in Chinese adults in Hong Kong. DESIGN, SETTING AND PARTICIPANTS: Telephone
      surveys were conducted between 2009 and 2012, with 4553 randomly sampled Chinese
      adults (male 54%, mean age 58.3 years) in Hong Kong. MEASUREMENTS: Happiness was
      measured using the four-item Subjective Happiness Scale (SHS) and single-item
      Global Happiness Item (GHI). Smoking status was categorized as current smokers
      (7.7%%), ex-smokers (6.5%, 93% quit for >6 months) and never smokers (85.8%).
      Linear and ordinal logistic regressions were used to calculate adjusted beta
      coefficients for SHS and proportional adjusted odds ratios (aOR) for GHI in
      relation to smoking. FINDINGS: Compared with current smokers, ex-smokers enjoyed
      greater happiness according to both SHS (adjusted beta = 0.16, P < 0.05) and GHI
      (aOR = 1.52, P < 0.05) measurements, but current and never smokers were similar.
      Among current smokers, the number of cigarettes smoked was not associated with
      happiness, but the lack of any attempt to quit was associated significantly with
      greater happiness (adjusted beta = 0.31 for SHS, aOR = 1.82 for GHI) compared
      with smokers who had tried to quit but not succeeded. Smokers not intending to
      quit in the next 6 months had higher odds of happiness (GHI) than those wanting
      to quit within 6 months (aOR = 1.86, P < 0.05). CONCLUSIONS: Ex-smokers in Hong
      Kong are happier than current smokers and never smokers, whose happiness
      measurements are similar. Causal associations have yet to be established.

PMID- 24588871
TI  - Synthesis, identification and in vivo studies of tumor-targeting agent peptide
      doxorubicin (PDOX) to treat peritoneal carcinomatosis of gastric cancer with
      similar efficacy but reduced toxicity.
AB  - BACKGROUND: This work aimed to synthesize a cathepsin B (CTSB)-cleavable tumor
      targeting prodrug peptide doxorubicin (PDOX) and study the in vivo efficacy and
      toxicities on an animal model of gastric peritoneal carcinomatosis (PC). METHODS:
      PDOX was synthesized using doxorubicin (DOX) attaching to a CTSB-cleavable
      dipeptide Ac-Phe-Lys and a para-amino-benzyloxycarbonyl (PABC) spacer. PC model
      was established by injecting VX2 tumor cells into the gastric sub-mucosa of 40
      rabbits, which then were randomized into 4 groups: the Control (n = 10) without
      treatment, the HIPEC (n = 10) receiving cytoreductive surgery (CRS) plus
      hyperthermic intraperitoneal chemotherapy (HIPEC), the PDOX (n = 10) and the DOX
      (n = 10) receiving systemic chemotherapy with PDOX 50.0 mg/kg or DOX 5.0 mg/kg,
      respectively, after CRS + HIPEC. RESULTS: The median overall survivals (OS) were
      23.0 d (95% CI: 19.9 d - 26.1 d) in the Control, 41.0 d (36.9 d - 45.1 d) in the
      HIPEC, 65.0 d (44.1 d - 71.9 d) in the PDOX, and 58.0 d (39.6 d - 54.4 d) in the
      DOX. Compared with the Control, the OS was extended by 70% in the HIPEC (p <
      0.001) and further extended by 40% in the DOX (p = 0.029) and by 58% in the PDOX
      (p = 0.021), and the PC severity was decreased in the HIPEC and further decreased
      in the PDOX and DOX. Animals receiving DOX treatment showed hematological
      toxicities with marked reduction of white blood cells and platelets, as well as
      cardiac toxicities with significant increases in creatine kinase mb isoenzyme,
      evident myocardium coagulation necrosis, significant nuclear degeneration, peri
      nucleus mitochondria deletion, mitochondria-pyknosis, and abnormal intercalated
      discs. But these toxicities were not evident in the PDOX. CONCLUSIONS: PDOX is a
      newly synthesized tumor-targeting prodrug of DOX. Compared with DOX, PDOX has
      similar efficacy but reduced hematological and cardiac toxicities in treating
      rabbit model of gastric PC.

PMID- 24588873
TI  - Synthesis, mechanical properties, and in vitro biocompatibility with osteoblasts
      of calcium silicate-reduced graphene oxide composites.
AB  - Calcium silicate (CaSiO3, CS) ceramics are promising bioactive materials for bone
      tissue engineering, particularly for bone repair. However, the low toughness of
      CS limits its application in load-bearing conditions. Recent findings indicating
      the promising biocompatibility of graphene imply that graphene can be used as an
      additive to improve the mechanical properties of composites. Here, we report a
      simple method for the synthesis of calcium silicate/reduced graphene oxide
      (CS/rGO) composites using a hydrothermal approach followed by hot isostatic
      pressing (HIP). Adding rGO to pure CS increased the hardness of the material by
      ~40%, the elastic modulus by ~52%, and the fracture toughness by ~123%. Different
      toughening mechanisms were observed including crack bridging, crack branching,
      crack deflection, and rGO pull-out, thus increasing the resistance to crack
      propagation and leading to a considerable improvement in the fracture toughness
      of the composites. The formation of bone-like apatite on a range of CS/rGO
      composites with rGO weight percentages ranging from 0 to 1.5 has been
      investigated in simulated body fluid (SBF). The presence of a bone-like apatite
      layer on the composite surface after soaking in SBF was demonstrated by X-ray
      diffraction (XRD) and field emission scanning electron microscopy (FESEM). The
      biocompatibility of the CS/rGO composites was characterized using methyl thiazole
      tetrazolium (MTT) assays in vitro. The cell adhesion results showed that human
      osteoblast cells (hFOB) can adhere to and develop on the CS/rGO composites. In
      addition, the proliferation rate and alkaline phosphatase (ALP) activity of cells
      on the CS/rGO composites were improved compared with the pure CS ceramics. These
      results suggest that calcium silicate/reduced graphene oxide composites are
      promising materials for biomedical applications. 

PMID- 24588874
TI  - Incorporating quality assessments of primary studies in the conclusions of
      diagnostic accuracy reviews: a cross-sectional study.
AB  - BACKGROUND: Drawing conclusions from systematic reviews of test accuracy studies
      without considering the methodological quality (risk of bias) of included studies
      may lead to unwarranted optimism about the value of the test(s) under study. We
      sought to identify to what extent the results of quality assessment of included
      studies are incorporated in the conclusions of diagnostic accuracy reviews.
      METHODS: We searched MEDLINE and EMBASE for test accuracy reviews published
      between May and September 2012. We examined the abstracts and main texts of these
      reviews to see whether and how the results of quality assessment were linked to
      the accuracy estimates when drawing conclusions. RESULTS: We included 65 reviews
      of which 53 contained a meta-analysis. Sixty articles (92%) had formally assessed
      the methodological quality of included studies, most often using the original
      QUADAS tool (n = 44, 68%). Quality assessment was mentioned in 28 abstracts
      (43%); with a majority (n = 21) mentioning it in the methods section. In only 5
      abstracts (8%) were results of quality assessment incorporated in the
      conclusions. Thirteen reviews (20%) presented results of quality assessment in
      the main text only, without further discussion. Forty-seven reviews (72%)
      discussed results of quality assessment; the most frequent form was as
      limitations in assessing quality (n = 28). Only 6 reviews (9%) further linked the
      results of quality assessment to their conclusions, 3 of which did not conduct a
      meta-analysis due to limitations in the quality of included studies. In the
      reviews with a meta-analysis, 19 (36%) incorporated quality in the analysis.
      Eight reported significant effects of quality on the pooled estimates; in none of
      them these effects were factored in the conclusions. CONCLUSION: While almost all
      recent diagnostic accuracy reviews evaluate the quality of included studies, very
      few consider results of quality assessment when drawing conclusions. The practice
      of reporting systematic reviews of test accuracy should improve if readers not
      only want to be informed about the limitations in the available evidence, but
      also on the associated implications for the performance of the evaluated tests.

PMID- 24588875
TI  - Geriatric conditions as predictors of increased number of hospital admissions and
      hospital bed days over one year: findings of a nationwide cohort of older adults
      from Taiwan.
AB  - The main aim of the present study was to determine whether geriatric conditions
      independently predict hospital utilizations after controlling for chronic
      diseases and disability among community dwelling older adults. We analyzed data
      from a nationally representative sample of older adults aged 65 years and above
      by linkage of 2005 Taiwan National Health Interview Survey data (including
      demographic characteristics, chronic diseases, disability, and geriatric
      conditions such as depressive symptoms, cognitive impairment, falls, and urinary
      incontinence), and 2006 National Health Insurance (NHI) claims data (including
      hospital admissions and hospital bed days). A total of 1598 participants who
      consented to data linkage, were successfully linked to NHI data, and had complete
      data for geriatric conditions were eligible for analysis. The prevalence of
      depressive symptoms, cognitive impairment, falls, and urinary incontinence were
      20.6%, 26.1%, 21.3% and 23.9%, respectively. Overall, 18.2% (291/1598) of
      participants had at least one hospital admission during 2006. After adjustment
      for demographics, prior hospitalization, chronic diseases and functional
      disability, participants with geriatric conditions had significantly more
      hospital admissions (incidence rate ratio=1.34; 95% confidence interval=[1.02
      1.75]) and more hospital bed days (incidence rate ratio=1.72; 95% confidence
      interval=[1.11-2.66]) than participants without geriatric conditions. Our results
      highlight the high prevalence (56.3%) of one or more geriatric conditions and
      their independent association with excess hospital utilizations. Thus, it is of
      critical importance to develop programs aimed at preventing or improving these
      conditions to reduce hospital use in this population. 

PMID- 24588876
TI  - Laparoendoscopic single-site (LESS) vs laparoscopic living-donor nephrectomy: a
      systematic review and meta-analysis.
AB  - The aim of this study was to provide a systematic review and meta-analysis of
      reports comparing laparoendoscopic single-site (LESS) living-donor nephrectomy
      (LDN) vs standard laparoscopic LDN (LLDN). A systematic review of the literature
      was performed in September 2013 using PubMed, Scopus, Ovid and The Cochrane
      library databases. Article selection proceeded according to the search strategy
      based on Preferred Reporting Items for Systematic Reviews and Meta-analyses
      criteria. Weighted mean differences (WMDs) were used to measure continuous
      variables and odds ratios (ORs) to measure categorical ones. Nine publications
      meeting eligibility criteria were identified, including 461 LESS LDN and 1006
      LLDN cases. There were more left-side cases in the LESS LDN group (96.5% vs
      88.6%, P < 0.001). Meta-analysis of extractable data showed that LLDN had a
      shorter operative time (WMD 15.06 min, 95% confidence interval [CI] 4.9-25.1; P =
      0.003), without a significant difference in warm ischaemia time (WMD 0.41 min,
      95% CI -0.02 to 0.84; P = 0.06). Estimated blood loss was lower for LESS LDN (WMD
      -22.09 mL, 95% CI -29.5 to -14.6; P < 0.001); however, this difference was not
      clinically significant. There was a greater likelihood of conversion for LESS LDN
      (OR 13.21, 95% CI 4.65-37.53; P < 0.001). Hospital stay was similar (WMD -0.11
      days, 95% CI -0.33 to 0.12; P = 0.35), as well as the visual analogue pain score
      at discharge (WMD -0.31, 95% CI -0.96 to 0.35; P = 0.36), but the analgesic
      requirement was lower for LESS LDN (WMD -2.58 mg, 95% CI -5.01 to -0.15; P =
      0.04). Moreover, there was no difference in the postoperative complication rate
      (OR 1.00, 95% CI 0.65-1.54; P = 0.99). Renal function of the recipient, as based
      on creatinine levels at 1 month, showed similar outcomes between groups (WMD 0.10
      mg/dL, -0.09 to 0.29; P = 0.29). In conclusion, LESS LDN represents an emerging
      option for living kidney donation. This procedure offers comparable surgical and
      early functional outcomes to the conventional LLDN, with a lower analgesic
      requirement. However, it is more technically challenging than LLDN, as shown by a
      greater likelihood of conversion. The role of LESS LDN remains to be defined. 

PMID- 24588877
TI  - Impact of nulliparous women's body mass index or excessive weight gain in
      pregnancy on genital tract trauma at birth.
AB  - INTRODUCTION: The purpose of this study was to explore the impact of body mass
      index (BMI) or pregnancy weight gain on the presence, site, and severity of
      genital tract trauma at childbirth in nulliparous women. METHODS: The present
      study is a subanalysis of a prospective cohort of healthy nulliparous women
      recruited during pregnancy and followed through birth. Weight gain during
      pregnancy and prepregnancy BMI were recorded. At birth, women underwent detailed
      mapping of genital tract trauma. For analyses, women were dichotomized into obese
      (BMI >= 30) versus nonobese (BMI < 30) at baseline as well as into those who
      gained weight as recommended by the Institute of Medicine (IOM) and those who
      gained more than the recommended amount to determine the impact of obesity or
      excessive weight gain on rates of genital tract trauma. RESULTS: Data from 445
      women were available for analysis. Presence and severity of genital tract trauma
      did not vary between obese and nonobese women (51% vs 53%, P = .64). Likewise,
      women who had more than the IOM-recommended weight gain did not have a higher
      incidence of perineal lacerations (52% versus 53% with perineal lacerations, P =
      .69). Obese women were more likely to gain in excess of the IOM guidelines during
      pregnancy (75% vs 50% excessive weight gain in obese vs nonobese women,
      respectively; P < .001). DISCUSSION: A woman's BMI or excessive weight gain in
      pregnancy did not influence her risk of genital tract trauma at birth.

PMID- 24588878
TI  - Midwifery care in rural and remote British Columbia: a retrospective cohort study
      of perinatal outcomes of rural parturient women with a midwife involved in their
      care, 2003 to 2008.
AB  - INTRODUCTION: Midwifery has been regulated and publicly funded in British
      Columbia since 1998. Midwives are currently concentrated in urban areas; access
      to care is limited in rural communities. Rural midwifery practice can be
      challenging because of low birth numbers, solo practice, lack of on-site
      cesareans and specialist backup, and interprofessional tensions resulting from
      the integration of midwives into rural maternity care systems. Despite these
      barriers, rural midwives have made a substantial contribution to rural maternity
      care in British Columbia. The purpose of this retrospective cohort study is to
      examine outcomes of midwife-involved births in rural British Columbia in the
      postregionalization era. METHODS: We analyzed the outcomes of all parturient
      women with postal codes outside of the core urban areas of the province, and
      their singleton infants without a diagnosed congenital anomaly, who had a midwife
      involved in their care between April 1, 2003, and March 31, 2008. Outcomes are
      reported for 6 obstetric service levels. Service levels are assigned to
      parturient women via maternal postal codes. Women who reside further than 60
      minutes from a hospital with maternity services were assigned a distance category
      (2 levels: >2 hours, 1-2 hours); women residing within one hour of a hospital
      with maternity services were assigned the level of service available at their
      catchment hospital (4 levels, ranging from maternity care without cesarean to
      cesarean provided by general surgeons or obstetricians). RESULTS: Eight percent
      of rural parturient women had a midwife involved in their care. Rates of planned
      home birth exceeded the provincial average (26.1%) in 5 of the 6 service levels.
      Rates of actual home birth were lowest among women who resided 2 or more hours
      away from maternity services. Obstetric intervention rates were lower for women
      residing in communities without cesareans or with intermittent access to
      cesareans. The prevalence of adverse neonatal outcomes was very low across
      service levels; perinatal mortality was elevated among women residing in
      communities more than 2 hours away from services. DISCUSSION: Despite numerous
      challenges, midwives provide safe maternity care to rural parturient women and
      offer choice of birth place. Given the difficulty of recruiting and retaining
      maternity care providers to rural settings in British Columbia and across Canada,
      these findings open the door for a more sustained planning process involving
      midwives in rural communities. Reasons for the elevated perinatal mortality rate
      among women who live more than 2 hours away from services should be explored in
      more detail, perhaps via in-depth interviews with rural midwives who serve this
      population.

PMID- 24588879
TI  - The effects of intimate partner violence duration on individual and partner
      related sexual risk factors among women.
AB  - INTRODUCTION: Intimate partner violence (IPV) is associated with risk of sexually
      transmitted infections (STIs) and HIV among women, but less is known about
      mechanisms of this association and if length of relationship violence is a
      factor. The purpose of this study was to explore the relationship between the
      duration of IPV and both individual and partner-related sexual risk factors that
      may increase women's risk for STIs and HIV. METHODS: This was a secondary
      analysis of data collected from the medical records of 2000 women. Four distinct
      categories defined the duration of partner violence: violence in the past year
      only, past year and during the past 5 years, past year plus extending for greater
      than 5 years, and no past year violence but a history of partner violence.
      Logistic regression models were used to examine the associations between the
      duration of partner violence and individual sexual risk behaviors (eg, number of
      sexual partners, drug and/or alcohol use, anal sex) and partner-related sexual
      risk factors (eg, nonmonogamy, STI risk, condom nonuse). RESULTS: Nearly 30% of
      the women in the study reported a history of partner violence during their
      lifetime. All of the individual risk factors, as well as partner-related risk
      factors, were significantly associated (P < .05) with partner violence and
      duration of violence. DISCUSSION: The study findings extend the knowledge related
      to partner violence as a risk factor for STIs/HIV, highlighting the effects of
      partner violence duration on the health of women. Assessing for lifetime
      experiences of partner violence may improve outcomes for women and their
      families.

PMID- 24588880
TI  - The 2012 American College of Nurse-Midwives core competencies for basic midwifery
      practice: history and revision.
AB  - The American College of Nurse-Midwives (ACNM) Core Competencies for Basic
      Midwifery Practice, approved in 2012, (hereafter referred to as Core
      Competencies) outline the knowledge, skills, and abilities that can be expected
      of new certified nurse-midwives (CNMs) and certified midwives (CMs). The Core
      Competencies are standards for midwifery education, and the document is an
      important guide for midwifery practice and policy. As a part of the 2012
      revision, the Basic Competency Section of the ACNM Division of Education reviewed
      a variety of national and international documents to ensure that the basic
      education of CNMs/CMs is consistent with the practice of midwives in the United
      States and internationally. Few substantive changes were made to the document,
      but several areas were adjusted and clarified. New graduates continue to be
      prepared by midwifery education programs to provide safe, evidence-based
      midwifery care to women across the lifespan, well newborns up to 28 days, and
      sexual partners of women diagnosed with sexually transmitted infections. 

PMID- 24588881
TI  - Umbilical cord avulsion in waterbirth.
AB  - Umbilical cord avulsion (or "cord snapping") is often cited as a risk associated
      with waterbirth. This article discusses a case study in which a cord avulsed
      during a waterbirth and uses it as a basis to explore the incidence, etiology,
      and associated risk factors of umbilical cord avulsion. The diagnosis, clinical
      presentation, and management of cord avulsion in waterbirth is presented along
      with a thorough review of the literature and relevant professional standards.
      This article offers recommendations for clinical practice to minimize the risk of
      a cord avulsion and highlights the need for additional research and provider
      education to ensure optimal care of women and newborns. 

PMID- 24588882
TI  - Current resources for evidence-based practice, Jan/Feb 2014.

PMID- 24588883
TI  - Study uses birth certificate data to refute safety of out-of-hospital birth.

PMID- 24588884
TI  - Maternal use of opioids near conception may increase risk of neural tube defects.

PMID- 24588885
TI  - Unsafe use of combined hormonal contraceptives poses health risks for women with
      medical conditions.

PMID- 24588887
TI  - Outcomes of Latina women in centeringpregnancy group prenatal care compared with
      individual prenatal care.

PMID- 24588888
TI  - Outcomes of Latina women in centeringpregnancy group prenatal care compared with
      individual prenatal care. In reply.

PMID- 24588891
TI  - Biosynthetic genes and activity spectrum of antifungal polyynes from Collimonas
      fungivorans Ter331.
AB  - The antifungal activity of bacteria from the genus Collimonas has been well
      documented, but the chemistry and gene functions that underlie this phenotype are
      still poorly understood. Screening of a random plasposon insertion library of
      Collimonas fungivorans Ter331 for loss-of-function mutants revealed the
      importance of gene cluster K, which is annotated to code for the biosynthesis of
      a secondary metabolite and which features genes for fatty acid desaturases and
      polyketide synthases. Mutants in gene cluster K had lost the ability to inhibit
      hyphal growth of the fungus Aspergillus niger and were no longer able to produce
      and secrete several metabolites that after extraction and partial purification
      from wildtype strain Ter331 were shown to share a putative ene-triyne moiety.
      Some but not all of these metabolites were able to inhibit growth of A. niger,
      indicating functional variation within this group of Collimonas-produced polyyne
      like 'collimomycins'. Polymerase chain reaction analysis of isolates representing
      different Collimonas species indicated that the possession of cluster K genes
      correlated positively with antifungal ability, further strengthening the notion
      that this cluster is involved in collimomycin production. We discuss our findings
      in the context of other bacterially produced polyynes and the potential use of
      collimomycins for the control of harmful fungi. 

PMID- 24588890
TI  - New extremophilic lipases and esterases from metagenomics.
AB  - Lipolytic enzymes catalyze the hydrolysis of ester bonds in the presence of
      water. In media with low water content or in organic solvents, they can catalyze
      synthetic reactions such as esterification and transesterification. Lipases and
      esterases, in particular those from extremophilic origin, are robust enzymes,
      functional under the harsh conditions of industrial processes owing to their
      inherent thermostability and resistance towards organic solvents, which combined
      with their high chemo-, regio- and enantioselectivity make them very attractive
      biocatalysts for a variety of industrial applications. Likewise, enzymes from
      extremophile sources can provide additional features such as activity at extreme
      temperatures, extreme pH values or high salinity levels, which could be
      interesting for certain purposes. New lipases and esterases have traditionally
      been discovered by the isolation of microbial strains producing lipolytic
      activity. The Genome Projects Era allowed genome mining, exploiting homology with
      known lipases and esterases, to be used in the search for new enzymes. The
      Metagenomic Era meant a step forward in this field with the study of the
      metagenome, the pool of genomes in an environmental microbial community. Current
      molecular biology techniques make it possible to construct total environmental
      DNA libraries, including the genomes of unculturable organisms, opening a new
      window to a vast field of unknown enzymes with new and unique properties. Here,
      we review the latest advances and findings from research into new extremophilic
      lipases and esterases, using metagenomic approaches, and their potential
      industrial and biotechnological applications. 

PMID- 24588892
TI  - Dermoscopic features of cutaneous melanoma are associated with clinical
      characteristics of patients and tumours and with MC1R genotype.
AB  - BACKGROUND: Several algorithms are available for the dermoscopic diagnosis of
      pigmented skin lesions. The MC1R gene is a key determinant of pigmentation
      characteristics that are established host-related melanoma risk factors.
      OBJECTIVES: To investigate the association of dermoscopic features of sporadic
      cutaneous melanomas with clinical characteristics of patients and corresponding
      tumours and with genetic changes in the MC1R and BRAF genes. METHODS: A total of
      64 dermoscopic images of 62 patients were scored by ABCD rule and modified
      pattern analysis. Detailed patients' and melanomas' characteristics were
      collected. Patients were screened for germline MC1R variants and related
      melanomas for somatic V600 BRAF mutations. RESULTS: A lower total dermoscopic
      score (TDS) was observed in melanomas of patients with red hair (P = 0.019), due
      to reduced dermoscopic structures (P < 0.0001). Thicker melanomas showed higher
      TDS values (P = 0.021) due to sharper borders (P < 0.0001) and higher number of
      colors (P = 0.004). An atypical pigment network was prevalent in superficial
      spreading melanomas (P = 0.010), in individuals with dark skin (P = 0.043) and
      hair color (P = 0.001). An atypical vascular pattern was more frequent in nodular
      (P < 0.0001) and thick (P < 0.0001) melanomas, in individuals with skin type I-II
      (P = 0.037), blond or red hair color (P = 0.032) and blue or green eyes (P =
      0.014). Melanomas of MC1R R carriers showed lower TDS value (P = 0.037), reduced
      dermoscopic structures (P = 0.001) and lower prevalence of atypical pigment
      network (P = 0.001). No differences were identified between BRAF-mutated or wild
      type melanomas. CONCLUSIONS: We suggest a phenotypic/MC1R profile for melanoma
      patients and their tumours. Melanomas of MC1R R carriers show a significant lower
      TDS value, with reduced dermoscopic structures, and a lower prevalence of an
      atypical pigment network. Non-carriers of MC1R R variants develop melanomas
      dermoscopically characterized by an atypical pigment network which is prevalent
      in superficial spreading melanomas, in patients with dark complexion and less
      frequent in red-haired individuals.

PMID- 24588893
TI  - Improving coronary heart disease self-management using mobile technologies
      (Text4Heart): a randomised controlled trial protocol.
AB  - BACKGROUND: Cardiac rehabilitation (CR) is a secondary prevention program that
      offers education and support to assist patients with coronary heart disease (CHD)
      make lifestyle changes. Despite the benefits of CR, attendance at centre-based
      sessions remains low. Mobile technology (mHealth) has potential to reach more
      patients by delivering CR directly to mobile phones, thus providing an
      alternative to centre-based CR. The aim of this trial is to evaluate if a mHealth
      comprehensive CR program can improve adherence to healthy lifestyle behaviours
      (for example, physically active, fruit and vegetable intake, not smoking, low
      alcohol consumption) over and above usual CR services in New Zealand adults
      diagnosed with CHD. METHODS/DESIGN: A two-arm, parallel, randomised controlled
      trial will be conducted at two Auckland hospitals in New Zealand. One hundred
      twenty participants will be randomised to receive a 24-week evidence- and theory
      based personalised text message program and access to a supporting website in
      addition to usual CR care or usual CR care alone (control). The primary outcome
      is the proportion of participants adhering to healthy behaviours at 6 months,
      measured using a composite health behaviour score. Secondary outcomes include
      overall cardiovascular disease risk, body composition, illness perceptions, self
      efficacy, hospital anxiety/depression and medication adherence. DISCUSSION: This
      study is one of the first to examine an mHealth-delivered comprehensive CR
      program. Strengths of the trial include quality research design and in-depth
      description of the intervention to aid replication. If effective, the trial has
      potential to augment standard CR practices and to be used as a model for other
      disease prevention or self-management programs. TRIAL REGISTRY: Australian New
      Zealand Clinical Trials Registry: ACTRN12613000901707.

PMID- 24588895
TI  - CNS neurotoxicity of bacterial cellulose-poly(acrylamide-sodium acrylate)
      hydrogel: a future therapeutic carrier.

PMID- 24588896
TI  - An evaluation of an express testing service for sexually transmissible infections
      in low-risk clients without complications.
AB  - Background One effective way of reducing the prevalence of sexually transmissible
      infections (STIs) in a population is ensuring easy access to clinical services
      and screening of populations at high risk of STIs, including HIV. We aimed to
      describe the features of clients using the express testing service (ETS) and the
      overall impact on the service. METHODS: This retrospective cross-sectional study
      involved all clients attending the walk-in triage service at Melbourne Sexual
      Health Centre before the introduction of ETS in 2009 and after ETS (2011 and
      2012). RESULTS: There were 32?720 and 82?265 consultations before and after ETS
      respectively. The ETS saw 4387 (9%) of 55?648 consultations (excluding
      appointments and results), giving rise to a fall in the proportion of lower-risk
      clients having full consultations (from 53% to 50% of consultations; P<0.001).
      The consultations testing for HIV and chlamydia (Chlamydia trachomatis) were
      marginally higher (HIV: 48% v. 47%, P=0.017; chlamydia: 70% v. 68%, P=0.015) with
      ETS. Young (26 v. 27 years) females (38% v. 34%) utilised the ETS more (P<0.001).
      The time taken for consultation and the total time spent in the clinic was
      significantly decreased during the ETS period (from 25min to 6min for
      consultation time and from 59min to 29min for total clinic time; P<0.001).
      CONCLUSIONS: The data suggest that fast-track services such as ETS are effective
      in increasing access for higher-risk individuals while streamlining screening of
      asymptomatic low-risk clients.

PMID- 24588894
TI  - TAR DNA-binding protein 43 pathology in Alzheimer's disease with psychosis.
AB  - BACKGROUND: TAR DNA-binding protein 43 (TDP-43) has been identified as a major
      disease protein in frontotemporal lobar degeneration. More recently, TDP-43
      proteinopathy has also been observed in Alzheimer's disease (AD) with a
      characteristic distribution of TDP-43 predominantly in the mesial temporal lobe,
      and to a lesser degree in the neocortical areas. AD subjects with psychotic
      symptoms (AD+P) represent a subgroup characterized by greater impairment of
      frontal cortex-dependent cognitive functions and more severe frontal cortical
      neuropathology. The aim of this study is to determine whether there is an
      association between TDP-43 pathology and AD+P. We hypothesized that TDP-43
      pathology would be more frequent in AD+P than in AD without psychosis. METHODS:
      We studied the presence and distribution of TDP-43 pathology by
      immunohistochemistry in the dentate gyrus (DG) and prefrontal cortex (FC) of
      postmortem brain specimens from 68 subjects with a primary neuropathologic
      diagnosis of AD as determined by the Neuropathology Core of the University of
      Pittsburgh Alzheimer's Disease Research Center. RESULTS: Forty-five (66%)
      subjects were classified as AD+P. Fourteen (20.6%) subjects had TDP-43 pathology
      in DG, eight (11.8%) had TDP-43 pathology in FC, and six (8.8%) had TDP-43
      pathology in both regions. TDP-43 in DG was not significantly associated with
      AD+P. However, TDP-43 in FC demonstrated a trend toward reduced likelihood of
      psychosis (p = 0.068). TDP-43 pathology in DG, but not FC, was significantly
      associated with greater age at death and longer duration of illness. CONCLUSIONS:
      Our findings indicate that there was no association between concomitant TDP-43
      pathology in DG or FC and AD+P.

PMID- 24588898
TI  - Integrative computational modeling of protein interactions.
AB  - Protein interactions define the homeostatic state of the cell. Our ability to
      understand these interactions and their role in both health and disease is tied
      to our knowledge of the 3D atomic structure of the interacting partners and their
      complexes. Despite advances in experimental method of structure determination,
      the majority of known protein interactions are still missing an atomic structure.
      High-resolution methods such as X-ray crystallography and NMR spectroscopy
      struggle with the high-throughput demand, while low-resolution techniques such as
      cryo-electron microscopy or small-angle X-ray scattering provide data that are
      too coarse. Computational structure prediction of protein complexes, or docking,
      was first developed to complement experimental research and has since blossomed
      into an independent and lively field of research. Its most successful products
      are hybrid approaches that combine powerful algorithms with experimental data
      from various sources to generate high-resolution models of protein complexes.
      This minireview introduces the concept of docking and docking with the help of
      experimental data, compares and contrasts the available integrative docking
      methods, and provides a guide for the experimental researcher for what types of
      data and which particular software can be used to model a protein complex. 

PMID- 24588897
TI  - CHRNA5 and CHRNA3 variants and level of neuroticism in young adult Mexican
      American men and women.
AB  - A lifetime history of alcohol dependence has been associated with elevations in
      neuroticism in Mexican American young adults. The identification of genetic
      markers associated with neuroticism and their influence on the development of
      alcohol use disorders (AUD) may contribute to our understanding of the
      relationship between personality traits and the increased risk of AUD in Mexican
      Americans. The purpose of this study was to investigate associations between
      neuroticism and 13 single nucleotide polymorphisms (SNPs) in the nicotinic
      acetylcholine (nAChR) alpha5-subunit (CHRNA5) and alpha3-subunit (CHRNA3) genes
      in young adult Mexican American men and women. Participants were 465 young adult
      Mexican American men and women who are literate in English and are residing
      legally in San Diego County. Each participant gave a blood sample and completed a
      structured diagnostic interview. Neuroticism was assessed using the Maudsley
      Personality Inventory. The minor alleles of four CHRNA5 polymorphisms (rs588765,
      rs601079, rs680244 and rs555018) and three CHRNA3 polymorphisms (rs578776,
      rs6495307 and rs3743078) showed associations with neuroticism. Several of these
      SNPs also displayed nominal associations with DSM-IV alcohol and nicotine
      dependence, but tests of mediation suggested that these relations could be
      partially explained by the presence of co-occurring neuroticism. These findings
      suggest that genetic variations in nicotinic receptor genes may influence the
      development of neuroticism, which in turn is involved in the development of AUDs
      and nicotine dependence in Mexican American young adults. 

PMID- 24588899
TI  - Charge generation measured for fullerene-helical nanofilament liquid crystal
      heterojunctions.
AB  - The helical nanofilament (HNF) liquid crystal phase is an ordered architecture
      exhibiting interesting properties for charge transport. It is a small molecule
      self-assembly of stacked and twisted crystalline layers, which form alignable
      organic nanorods with half the surface area of the filaments consisting of
      aromatic sublayer edges. HNFs mixed with an electron acceptor generate an
      intriguing network for photoinduced electron transfer (PET). In this work, we
      characterize the structure of the HNF phase as processed into thin films with
      transmission electron microscopy (TEM) and X-ray diffraction (XRD). Additionally,
      we measure the flash-photolysis time-resolved microwave conductivity (TRMC) in
      samples where the HNF phase is fabricated into heterojunctions with the
      fullerenes C60 and PC60BM, prototypical electron acceptors for organic
      photovoltaics. Two distinct microstructures of the thin films were identified and
      compared for PET. A near-unity charge generation yield is observed in a bilayer
      of HNFs with C60. Moreover, the HNF phase is shown to be 10* better at charge
      generation than a lamellar structuring of the same components. Thus, the HNF
      phase is shown to be a good charge-generation interface. 

PMID- 24588900
TI  - The thresholds for statistical and clinical significance - a five-step procedure
      for evaluation of intervention effects in randomised clinical trials.
AB  - BACKGROUND: Thresholds for statistical significance are insufficiently
      demonstrated by 95% confidence intervals or P-values when assessing results from
      randomised clinical trials. First, a P-value only shows the probability of
      getting a result assuming that the null hypothesis is true and does not reflect
      the probability of getting a result assuming an alternative hypothesis to the
      null hypothesis is true. Second, a confidence interval or a P-value showing
      significance may be caused by multiplicity. Third, statistical significance does
      not necessarily result in clinical significance. Therefore, assessment of
      intervention effects in randomised clinical trials deserves more rigour in order
      to become more valid. METHODS: Several methodologies for assessing the
      statistical and clinical significance of intervention effects in randomised
      clinical trials were considered. Balancing simplicity and comprehensiveness, a
      simple five-step procedure was developed. RESULTS: For a more valid assessment of
      results from a randomised clinical trial we propose the following five-steps: (1)
      report the confidence intervals and the exact P-values; (2) report Bayes factor
      for the primary outcome, being the ratio of the probability that a given trial
      result is compatible with a 'null' effect (corresponding to the P-value) divided
      by the probability that the trial result is compatible with the intervention
      effect hypothesised in the sample size calculation; (3) adjust the confidence
      intervals and the statistical significance threshold if the trial is stopped
      early or if interim analyses have been conducted; (4) adjust the confidence
      intervals and the P-values for multiplicity due to number of outcome comparisons;
      and (5) assess clinical significance of the trial results. CONCLUSIONS: If the
      proposed five-step procedure is followed, this may increase the validity of
      assessments of intervention effects in randomised clinical trials.

PMID- 24588901
TI  - Investigation on distribution of airborne fungi in outdoor environment in Tehran,
      Iran.
AB  - BACKGROUND: Airborne fungi are responsible for the majority of fungal infections
      in humans and animals. Outdoor air markedly influences the prevalence of fungal
      spore levels in indoor air and thus, it is the major source of fungal infections
      in indoor environments especially in hospitalized individuals. METHODS: Using a
      settle plate method, air sampling (1092 air samples from 93 sampling sites in 22
      geographic regions of Tehran) was performed by exposing 90 mm settle plates
      containing Malt extract agar and Potato dextrose agar to the air for 30 min. The
      plates were incubated at 28 degrees C for 2-3 weeks and examined daily for
      visible fungal growth. Purified fungal colonies were identified at the genus
      level based on morphological criteria according to standard methods. RESULTS: A
      total of 6455 colonies belonging to 24 different fungal genera were isolated.
      Area V situated in the city center was the most contaminated region with 2523
      fungal colonies (39.1%), while area IV in the West showed the least contamination
      rate (636 colonies; 9.8%). Airborne fungi isolated were classified into 4 classes
      including hyaline Hyphomycetes (53.5%), dematiaceous Hyphomycetes (41.6%),
      Zygomycetes (2.8%) and Coelomycetes (0.2%). Aspergillus (31.3%) was the most
      prominent isolated fungus followed by Cladosporium (22.1%), Penicillium (13.8%)
      and Alternaria (12.2%). CONCLUSION: Our results indicate that outdoor air is a
      potential threat to public health because of harboring a wide array of pathogenic
      and allergenic airborne fungal spores which can serve as the main source of
      contamination of indoor environments such as homes, offices and hospitals.

PMID- 24588902
TI  - Editorial: 'slaying the myth' of the overqualified nurse: the graduate nurse and
      older people.

PMID- 24588903
TI  - Editorial: chronic kidney disease and the ageing population.

PMID- 24588904
TI  - BSACI guideline for the diagnosis and management of cow's milk allergy.
AB  - This guideline advises on the management of patients with cow's milk allergy.
      Cow's milk allergy presents in the first year of life with estimated population
      prevalence between 2% and 3%. The clinical manifestations of cow's milk allergy
      are very variable in type and severity making it the most difficult food allergy
      to diagnose. A careful age- and disease-specific history with relevant allergy
      tests including detection of milk-specific IgE (by skin prick test or serum
      assay), diagnostic elimination diet, and oral challenge will aid in diagnosis in
      most cases. Treatment is advice on cow's milk avoidance and suitable substitute
      milks. Cow's milk allergy often resolves. Reintroduction can be achieved by the
      graded exposure, either at home or supervised in hospital depending on severity,
      using a milk ladder. Where cow's milk allergy persists, novel treatment options
      may include oral tolerance induction, although most authors do not currently
      recommend it for routine clinical practice. Cow's milk allergy must be
      distinguished from primary lactose intolerance. This guideline was prepared by
      the Standards of Care Committee (SOCC) of the British Society for Allergy and
      Clinical Immunology (BSACI) and is intended for clinicians in secondary and
      tertiary care. The recommendations are evidence based, but where evidence is
      lacking the panel of experts in the committee reached consensus. Grades of
      recommendation are shown throughout. The document encompasses epidemiology,
      natural history, clinical presentations, diagnosis, and treatment. 

PMID- 24588906
TI  - A comparison of aphasia therapy outcomes before and after a Very Early
      Rehabilitation programme following stroke.
AB  - BACKGROUND: Very early aphasia rehabilitation studies have shown mixed results.
      Differences in therapy intensity and therapy type contribute significantly to the
      equivocal results. AIMS: To compare a standardized, prescribed very early aphasia
      therapy regimen with a historical usual care control group at therapy completion
      (4-5 weeks post-stroke) and again at follow-up (6 months). METHODS & PROCEDURES:
      This study compared two cohorts from successive studies conducted in four
      Australian acute/sub-acute hospitals. The studies had near identical recruitment,
      blinded assessment and data-collection protocols. The Very Early Rehabilitation
      (VER) cohort (N = 20) had mild-severe aphasia and received up to 20 1-h sessions
      of impairment-based aphasia therapy, up to 5 weeks. The control cohort (n = 27)
      also had mild-severe aphasia and received usual care (UC) therapy for up to 4
      weeks post-stroke. The primary outcome measure was the Aphasia Quotient (AQ) and
      a measure of communicative efficiency (DA) at therapy completion. Outcomes were
      measured at baseline, therapy completion and 6 months post-stroke and were
      compared using Generalised Estimating Equations (GEE) models. OUTCOMES & RESULTS:
      After controlling for initial aphasia and stroke disability, the GEE models
      demonstrated that at the primary end-point participants receiving VER achieved
      18% greater recovery on the AQ and 1.5% higher DA scores than those in the
      control cohort. At 6 months, the VER participants maintained a 16% advantage in
      recovery on the AQ and 0.6% more on DA scores over the control cohort
      participants. CONCLUSIONS & IMPLICATIONS: A prescribed, impairment-based aphasia
      therapy regimen, provided daily in very early post-stroke recovery, resulted in
      significantly greater communication gains in people with mild-severe aphasia at
      completion of therapy and at 6 months, when compared with a historical control
      cohort. Further research is required to demonstrate large-scale and long-term
      efficacy.

PMID- 24588907
TI  - Septic arthritis in ACL reconstruction surgery with hamstring autografts. Eleven
      years of experience.
AB  - BACKGROUND: Knee joint infection after ACL reconstruction is a rare complication
      with a low reported incidence, but the consequences can be devastating. The
      purpose of the study was to determine the incidence of septic arthritis after
      primary ACL reconstruction with hamstring auto-graft and the risk factors that
      may be associated. METHOD: A retrospective study of all primary ACL
      reconstruction from January 2000 to May 2011. Electronic medical records were
      reviewed to determine the number of infections, operating time, associated
      procedure, time of presentation after surgery, infection treatment,
      microbiological cultures and graft retention. At the end of the follow-up (18
      108months) a functional assessment of all the infected patients was performed
      using the Lysholm score with the Lysholm score. RESULTS: We analyzed 1564 cases
      of primary ACL reconstruction with hamstring autograft, of which seven cases were
      diagnosed with postoperative joint infection (incidence rate of 0.45%). The
      infectious agent most frequently isolated was a coagulase-negative
      Staphylococcus. Neither intraoperative factors nor age correlated with the
      development of the infection. The average Lysholm score was 95 points (range 89
      100 points). All but two patients retained their reconstructed ACL. The results
      of the five patients in which the graft was preserved were significantly better
      than the two patients that had their grafts removed (p=0.03). CONCLUSION: We
      conclude that septic arthritis post ACL reconstruction has a low incidence rate,
      which if handled at an early stage allows the patients a satisfactory return to
      their previous activities. Graft retention is important to obtain better
      functional results. LEVEL OF EVIDENCE: IV.

PMID- 24588905
TI  - Efficacy of zoledronic acid for chronic low back pain associated with Modic
      changes in magnetic resonance imaging.
AB  - BACKGROUND: Modic changes (MC) are associated with low back pain (LBP), but
      effective treatments are lacking. The aim of this randomized, placebo-controlled,
      double-blinded trial was to evaluate the efficacy of zoledronic acid (ZA) for
      chronic LBP among patients with MC in magnetic resonance imaging (MRI). METHODS:
      Inclusion criteria were LBP lasting >=3 months, with an intensity of >=6 on a 10
      cm VAS or an Oswestry Disability Index (ODI) of >=30%, and MC in MRI. Patients
      were randomized into single intravenous infusion of ZA 5 mg (n = 20), or placebo
      (n = 20) groups. The primary outcome was LBP intensity, secondary outcomes leg
      pain intensity, ODI, health-related quality of life (RAND-36), lumbar
      flexibility, sick leaves and use of pain medication. The treatment differences at
      one month and one year were analysed using ANCOVA with adjustment for the
      baseline score. RESULTS: The mean difference (MD) between the groups in the
      primary outcome, intensity of LBP, was 1.4 (95% confidence intervals (CI) 0.01 to
      2.9) in favour of ZA at one month. We observed no significant between-group
      difference in the intensity of LBP at one year (MD 0.7; 95% CI -1.0 to 2.4) or in
      secondary outcomes at any time point except that 20% of patients in the ZA group
      used non-steroidal anti-inflammatory drugs at one year compared to 60% in the
      placebo group (P = 0.022). Acute phase reactions (fever, flu-like symptoms,
      arthralgia) emerged in 95% of the patients in the ZA group, compared to 35% in
      the placebo group. CONCLUSIONS: ZA was effective in reducing the intensity of LBP
      in the short term and in reducing the use of NSAIDs within the time span of one
      year among patients with chronic LBP and MC confirmed in MRI. Although the
      results seem encouraging, larger studies are required to analyse the
      effectiveness and safety of ZA for patients with MC. TRIAL REGISTRATION:
      ClinicalTrial.gov identifier NCT01330238.

PMID- 24588908
TI  - MEK targeting in N-RAS mutated metastatic melanoma.
AB  - BACKGROUND: Gain of function mutations in B-RAF and N-RAS occur frequently in
      melanoma, leading to mitogen activating protein kinase (MAPK) pathway activation,
      and this pathway is the target of drugs in development. Our purpose was to study
      clinical characteristics of patients with mutations in this pathway and to
      determine activity of inhibitors of B-RAF and MEK in short term cultures grown
      from tumors of some of these patients. METHODS: Clinical and pathologic data were
      collected retrospectively on melanoma patients tested for B-RAF and N-RAS
      mutations at the Yale Cancer Center and associations with survival were
      determined. We studied in vitro activity of the pan-RAF inhibitor, RAF265, and
      the MEK inhibitor, MEK162, in 22 melanoma short term cultures. We further
      characterized the effect of MEK inhibition on apoptosis and growth of melanoma
      cultures. RESULTS: In a cohort of 144 metastatic melanoma patients we found that
      patients with N-RAS mutant melanoma had a worse prognosis. These patients were
      more likely to have brain metastases at the time of presentation with metastatic
      disease than their N-RAS-wild-type counterparts. All N-RAS mutant melanoma
      cultures tested in our study (n = 7) were sensitive to MEK inhibition 162.
      Exposure to MEK162 reduced ERK1/2 phosphorylation, and induced apoptosis.
      Clonogenic survival was significantly reduced in sensitive melanoma cell
      cultures. CONCLUSIONS: The prognosis of patients with melanoma expressing
      constitutively active N-RAS is poor, consistent with studies performed at other
      institutions. N-RAS mutant melanoma cultures appear to be particularly sensitive
      to MEK162, supporting ongoing clinical trials with MEK162 in N-RAS mutated
      melanoma.

PMID- 24588910
TI  - Reducing maternal and perinatal mortality through a community collaborative
      approach: introduction to a special issue on the Maternal and Newborn Health in
      Ethiopia Partnership (MaNHEP).

PMID- 24588909
TI  - Long-acting versus standard non-ergot dopamine agonists in Parkinson's disease: a
      meta-analysis of randomized controlled trials.
AB  - AIMS: To evaluate the efficacy, tolerability, and safety of long-acting versus
      standard non-ergot dopamine agonists (NEDAs) in Parkinson's disease (PD), we
      performed a meta-analysis of randomized controlled trials (RCTs). MATERIALS AND
      METHODS: The PubMed, EMBASE, Cochrane Library databases, and Web of Knowledge
      were searched up to November 20th 2013. The pooled weighted mean differences
      (WMDs) and relative risks (RRs) with 95% confidence intervals (CIs) were
      calculated. RESULTS: Eight large-scale RCTs, involving 2402 patients, were
      included in this meta-analysis. Compared with the standard NEDAs, long-acting
      NEDAs exhibited similar improvements in Unified Parkinson's Disease Rating Scale
      activities of daily living (ADL) score (WMD 0.09, 95% CI -0.33 to 0.50), motor
      score (WMD -0.35, 95% CI -1.60 to 0.90), and "off" time (WMD 0.18, 95% CI -0.14
      to 0.50). No differences were found in overall withdrawals (RR 1.11, 95% CI 0.94
      to 1.32), withdrawals due to adverse events (RR 1.19, 95% CI 0.91 to 1.56), or
      the ten commonly reported adverse events between the two formulations.
      CONCLUSIONS: Our meta-analysis showed long-acting NEDAs were noninferior to
      standard NEDAs in efficacy, tolerability, and safety in the treatment of PD.

PMID- 24588911
TI  - An evaluation of equitable access to a community-based maternal and newborn
      health program in rural Ethiopia.
AB  - INTRODUCTION: The Maternal and Newborn Health in Ethiopia Partnership (MaNHEP)
      aimed to promote equitable access to safe childbirth and postnatal care through a
      community-based educational intervention. This study evaluates the extent to
      which MaNHEP reached women who are socially and materially disadvantaged and,
      thus, at high risk for inadequate access to care. METHODS: The data used in this
      analysis are from MaNHEP's cross-sectional 2010 baseline and 2012 endline surveys
      of women who gave birth in the prior year. A logistic regression model was fit to
      examine the effects of sociodemographic characteristics on participation in the
      MaNHEP program. Descriptive statistics of select characteristics by birth and
      postnatal care provider were also calculated to explore trends in services use.
      RESULTS: Using data from the endline survey (N = 1019), the regression model
      showed that age, parity, education, and geographic residence were not
      significantly associated with MaNHEP exposure. However, women who were materially
      disadvantaged were still less likely to have participated in the program than
      their better-off counterparts. From the baseline survey (N = 1027) to the endline
      survey, women's use of skilled and semiskilled providers for birth care and
      postnatal care increased substantially, while use of untrained providers or no
      provider decreased. These shifts were greater for women with less personal wealth
      than for women with more personal wealth. DISCUSSION: MaNHEP appears to have
      succeeded in meeting its equity goals to a degree. However, this study also
      supports the intractable relationship between wealth inequality and access to
      maternal and newborn health services. Strategies targeting the poor in diverse
      contexts may eventually prove consistently effective in equitable services
      delivery. Until that time, a critical step that all maternal and newborn health
      programs can take is to monitor and evaluate to what extent they are reaching
      disadvantaged groups within the populations they serve.

PMID- 24588912
TI  - A qualitative study of attitudes and values surrounding stillbirth and neonatal
      mortality among grandmothers, mothers, and unmarried girls in rural Amhara and
      Oromiya regions, Ethiopia: unheard souls in the backyard.
AB  - INTRODUCTION: In Ethiopia, neonatal mortality and stillbirth are high and
      underreported. This study explored values related to neonatal mortality and
      stillbirth and the visibility of these deaths in rural Ethiopia among 3
      generations of women. METHODS: We conducted a qualitative study in 6 rural
      districts of the Oromiya and Amhara regional states during May 2012. We included
      30 focus groups representing grandmothers, married women (mothers), and unmarried
      girls in randomly selected kebeles (villages). RESULTS: Until the 40th day of
      life, neonates are considered to be strangers to the community (not human). Their
      deaths are not talked about; they are buried in the house or in the backyard.
      Mothers are forbidden to mourn their loss lest they offend God and bring on
      future neonatal losses. Women who repeatedly lose their neonates may be blamed,
      mistreated, and dishonored through divorce. Neonatal death and stillbirth are
      attributed to supernatural powers, although some women and girls associate these
      deaths with poverty and lack of education. The desire for increased visibility of
      neonatal death is mixed. Unlike the grandmothers and unmarried girls, most of the
      married women want death to be visible to draw the attention of policy makers.
      Women prefer home birth and consider themselves lucky to be able to give birth at
      home. At present, there is no national vital registration system. DISCUSSION:
      Neonatal death and stillbirth are hidden and the magnitude is likely
      underrepresented. The delayed recognition of personhood, attribution of death to
      supernatural causes, social repercussions for women who experience a pregnancy
      loss, preference for home birth, and lack of a vital registration system all
      contribute to the invisibility of perinatal deaths. Increasing the visibility of
      (and counting) these deaths may require multifaceted behavior-change
      interventions.

PMID- 24588913
TI  - Knowledge and skills retention among frontline health workers: community maternal
      and newborn health training in rural Ethiopia.
AB  - INTRODUCTION: We examined the degree to which the skills and knowledge of health
      workers in Ethiopia were retained 18 months after initial maternal and newborn
      health training and sought to identify factors associated with 18-month skills
      assessment performance. METHODS: A nonexperimental, descriptive design was
      employed to assess 18-month skills performance on the topics of Prevent Problems
      Before Baby Is Born and Prevent Problems After Baby Is Born. Assessment was
      conducted by project personnel who also received the maternal and newborn health
      training and additional training to reliably assess health worker performance.
      RESULTS: Among the 732 health workers who participated in maternal and newborn
      health training in 6 rural districts of the Amhara and Oromia regions of Ethiopia
      (including pretesting before training and a posttraining posttest), 75 health
      extension workers (78%) and 234 guide team members (37%) participated in 18-month
      posttest. Among health extension workers in both regions, strong knowledge
      retention was noted in 10 of 14 care steps for Prevent Problems Before Baby Is
      Born and in 14 of 16 care steps of Prevent Problems After Baby Is Born. Lower
      knowledge retention was observed among guide team members in the Amhara region.
      Across regions, health workers scored lowest on steps that involved nonaction
      (eg, do not give oxytocin). Educational attainment and age were among the few
      variables found to significantly predict test performance, although participants
      varied substantially by other sociodemographic characteristics. DISCUSSION:
      Results demonstrated an overall strong retention of knowledge and skills among
      health extension workers and highlighted the need for improvement among some
      guide team members. Refresher training and development of strategies to improve
      knowledge of retention of low-performing steps were recommended.

PMID- 24588914
TI  - Factors shaping interactions among community health workers in rural Ethiopia:
      rethinking workplace trust and teamwork.
AB  - INTRODUCTION: Worldwide, a shortage of skilled health workers has prompted a
      shift toward community-based health workers taking on greater responsibility in
      the provision of select maternal and newborn health services. Research in mid-
      and high-income settings suggests that coworker collaboration increases
      productivity and performance. A major gap in this research, however, is the
      exploration of factors that influence teamwork among diverse community health
      worker cadres in rural, low-resource settings. The purpose of this study is to
      examine how sociodemographic and structural factors shape teamwork among
      community-based maternal and newborn health workers in Ethiopia. METHODS: A cross
      sectional survey was conducted with health extension workers, community health
      development agents, and traditional birth attendants in 3 districts of the West
      Gojam Zone in the Amhara region of Ethiopia. Communities were randomly selected
      from Maternal and Newborn Health in Ethiopia Partnership (MaNHEP) sites; health
      worker participants were recruited using a snowball sampling strategy. Fractional
      logit modeling and average marginal effects analyses were carried out to identify
      the influential factors for frequency of work interactions with each cadre.
      RESULTS: One hundred and ninety-four health workers participated in the study. A
      core set of factors-trust in coworkers, gender, and cadre-were influential for
      teamwork across groups. Greater geographic distance and perception of self
      interested motivations were barriers to interactions with health extension
      workers, while greater food insecurity (a proxy for wealth) was associated with
      increased interactions with traditional birth attendants. DISCUSSION:
      Interventions that promote trust and gender sensitivity and improve perceptions
      of health worker motivations may help bridge the gap in health services delivery
      between low- and high-resource settings. Inter-cadre training may be one
      mechanism to increase trust and respect among diverse health workers, thereby
      increasing collaboration. Large-scale, longitudinal research is needed to
      understand how changes in trust, gender norms, and perceptions of motivations
      influence teamwork over time.

PMID- 24588915
TI  - The effect of community maternal and newborn health family meetings on type of
      birth attendant and completeness of maternal and newborn care received during
      birth and the early postnatal period in rural Ethiopia.
AB  - INTRODUCTION: Maternal and newborn deaths occur predominantly in low-resource
      settings. Community-based packages of evidence-based interventions and skilled
      birth attendance can reduce these deaths. The Maternal and Newborn Health in
      Ethiopia Partnership (MaNHEP) used community-level health workers to conduct
      prenatal Community Maternal and Newborn Health family meetings to build skills
      and care-seeking behaviors among pregnant women and family caregivers. METHODS:
      Baseline and endline surveys provided data on a random sample of women with a
      birth in the prior year. An intention-to-treat analysis, plausible net effect
      calculation, and dose-response analysis examined increases in completeness of
      care (mean percentage of 17 maternal and newborn health care elements performed)
      over time and by meeting participation. Regression models assessed the
      relationship between meeting participation, completeness of care, and use of
      skilled providers or health extension workers for birth care-controlling for
      sociodemographic and health service utilization factors. RESULTS: A 151% increase
      in care completeness occurred from baseline to endline. At endline, women who
      participated in 2 or more meetings had more complete care than women who
      participated in fewer than 2 meetings (89% vs 76% of care elements; P < .001). A
      positive dose-response relationship existed between the number of meetings
      attended and greater care completeness (P < .001). Women with any antenatal care
      were nearly 3 times more likely to have used a skilled provider or health
      extension worker for birth care. Women who had additionally attended 2 or more
      meetings with family members were over 5 times as likely to have used these
      providers, compared to women without antenatal care and who attended fewer than 2
      meetings (odds ratio, 5.19; 95% confidence interval, 2.88-9.36; P < .001).
      DISCUSSION: MaNHEP's family meetings complemented routine antenatal care by
      engaging women and family caregivers in self-care and care-seeking, resulting in
      greater completeness of care and more highly skilled birth care.

PMID- 24588916
TI  - Improving coverage of postnatal care in rural Ethiopia using a community-based,
      collaborative quality improvement approach.
AB  - INTRODUCTION: Ethiopia has high maternal and neonatal mortality and low use of
      skilled maternity care. The Maternal and Newborn Health in Ethiopia Partnership
      (MaNHEP), a 3.5-year learning project, used a community collaborative quality
      improvement approach to improve maternal and newborn health care during the birth
      to-48-hour period. This study examines how the promotion of community maternal
      and newborn health (CMNH) family meetings and labor and birth notification
      contributed to increased postnatal care within 48 hours by skilled providers or
      health extension workers. METHODS: Baseline and endline surveys, monthly quality
      improvement data, and MaNHEP's CMNH change package, a compendium of the most
      effective changes developed and tested by communities, were reviewed. Logistic
      regression assessed factors associated with postnatal care receipt. Monthly
      postnatal care receipt was plotted with control charts. RESULTS: The baseline (n
      = 1027) and endline (n = 1019) surveys showed significant increases in postnatal
      care, from 5% to 51% and from 15% to 47% in the Amhara and Oromiya regions,
      respectively (both P < .001). Notification of health extension workers for labor
      and birth within 48 hours was closely linked with receipt of postnatal care.
      Women with any antenatal care were 1.7 times more likely to have had a postnatal
      care visit (odds ratio [OR], 1.67; 95% confidence interval [CI], 1.10-2.54; P <
      .001). Women who had additionally attended 2 or more CMNH meetings with family
      members and had access to a health extension worker's mobile phone number were
      4.9 times more likely to have received postnatal care (OR, 4.86; 95% CI, 2.67
      8.86; P < .001). DISCUSSION: The increase in postnatal care far exceeds the 7%
      postnatal care coverage rate reported in the 2011 Ethiopian Demographic and
      Health Survey (EDHS). This result was linked to ideas generated by community
      quality improvement teams for labor and birth notification and cooperation with
      community-level health workers to promote antenatal care and CMNH family
      meetings.

PMID- 24588917
TI  - Improving maternal and newborn health care delivery in rural Amhara and Oromiya
      regions of Ethiopia through the Maternal and Newborn Health in Ethiopia
      Partnership.

PMID- 24588918
TI  - Use of mobile video show for community behavior change on maternal and newborn
      health in rural Ethiopia.
AB  - INTRODUCTION: A number of factors affect Ethiopia's efforts to meet Millennium
      Development Goals 4 and 5 to reduce maternal and newborn mortality. The Maternal
      and Newborn Health in Ethiopia Partnership (MaNHEP) project, as part of its
      overall strategy, implemented behavior change communication interventions to
      increase women's demand for and use of antenatal, birth, and postnatal services.
      Seeking to reach "media-dark" areas, MaNHEP implemented a mobile video show
      focused on maternal and newborn health. We report on the effect of the mobile
      video show on community knowledge, attitudes, and beliefs regarding maternal and
      newborn health, especially regarding care-seeking behavior and use of a skilled
      attendant for birth and postnatal care. METHODS: Two main data sources are used:
      qualitative data gathered through mobile video show participant discussions in 31
      randomly selected kebeles (villages with about 1000 households) and focus groups
      in 4 kebeles (2 from each region), and quantitative data generated from 510
      randomly selected adults participating in MaNHEP's endline survey. Qualitative
      data were thematically analyzed by the research team, and the accuracy of the
      transcriptions and categorization was also checked. RESULTS: The mobile video
      show reached a total of 28,389 mostly young or adult females in 51 kebeles. At
      endline, mobile video show attendees (vs nonattendees) reported significantly (P
      < .001) higher rates of recall of key MaNHEP messages about use of health
      extension workers for pregnancy registration, labor and birth notification, and
      postnatal care. Qualitative analysis yielded 3 overarching themes: mirrors to the
      community (the portrayal is accurate); call to action (we have to change this);
      and improvement ideas (suggested positive actions). DISCUSSION: The entertaining
      nature and local organization of the mobile video show event encouraged
      attendance. Building the video around recognizable characters (particularly the
      husbands) contributed to bringing about desired changes in people's knowledge and
      beliefs. Making the show readily available (through the mobile van) and bundling
      it with facilitated reflection sessions had a considerable impact on people's
      knowledge and confidence.

PMID- 24588919
TI  - A regional comparison of distribution strategies and women's awareness, receipt,
      and use of misoprostol to prevent postpartum hemorrhage in rural Amhara and
      Oromiya regions of Ethiopia.
AB  - INTRODUCTION: In Ethiopia, postpartum hemorrhage is a leading cause of maternal
      death. The Maternal Health in Ethiopia Partnership (MaNHEP) project developed a
      community-based model of maternal and newborn health focusing on birth and early
      postpartum care. Implemented in the Amhara and Oromiya regions, the model
      included misoprostol to prevent postpartum hemorrhage. This article describes
      regional trends in women's use of misoprostol; their awareness, receipt, and use
      of misoprostol at project's endline; and factors associated with its use.
      METHODS: The authors assessed trends in use of misoprostol using monthly data
      from MaNHEP's quality improvement database; and awareness, receipt, use, and
      correct use of misoprostol using data from MaNHEP's endline survey of 1019
      randomly sampled women who gave birth during the year prior to the survey.
      RESULTS: Misoprostol use increased rapidly and was relatively stable over 20
      months, but regional differences were stark. At endline, significantly more women
      in Oromiya were aware of misoprostol compared with women who resided in Amhara
      (94% vs 59%); significantly more had received misoprostol (80% vs 35%);
      significantly more had received it during pregnancy (93% vs 48%); and
      significantly more had received it through varied sources. Most women who
      received misoprostol used it (> 95%) irrespective of age, parity, or education.
      Factors associated with use were Oromiya residence (odds ratio [OR] 9.48; 95%
      confidence interval [CI], 6.78-13.24), attending 2 or more Community Maternal and
      Newborn Health (CMNH) family meetings (OR 2.62; 95% CI, 1.89-3.63), receiving
      antenatal care (OR 1.67; 95% CI, 1.08-2.58) and being attended at birth by a
      skilled provider or trained health extension worker, community health development
      agent, or traditional birth attendant versus an untrained caregiver or no one.
      Correct use was associated with having attended 2 or more CMNH family meetings
      (OR 2.02; 95% CI, 1.35-3.03). DISCUSSION: Multiple distribution channels increase
      women's access to misoprostol. Most women who have access to misoprostol use it.
      Early distribution to pregnant women who are educated to use misoprostol appears
      to be safe and unrelated to choice of birthplace.

PMID- 24588920
TI  - Interpretation of national policy regarding community-based use of misoprostol
      for postpartum hemorrhage prevention in Ethiopia: a tale of two regions.
AB  - INTRODUCTION: Postpartum hemorrhage (PPH) is responsible for a significant
      proportion of maternal mortality in developing countries. The uterotonic drug
      misoprostol (Cytotec) is a safe and effective means of preventing PPH. However,
      ministries of health in some countries are still grappling with policy that
      addresses the implementation of this targeted intervention in community settings
      and with communicating this policy throughout the health care system. The purpose
      of this study was to examine understandings of national policy for community
      based use of misoprostol to prevent PPH in 2 regions of Ethiopia: Amhara and
      Oromiya. METHODS: Qualitative in-depth interviews were conducted with a cohort of
      purposefully selected health officials (N = 51) representing various
      administrative levels of the Ministry of Health and influential nongovernmental
      organizations. Broad topics included national policy for PPH prevention, safety
      and effectiveness of community-based use of misoprostol, and preferences for
      misoprostol administration. Interview transcripts were analyzed for key concepts
      both across and within administrative levels. RESULTS: Among all officials,
      understandings of national policy for community-based PPH prevention using
      misoprostol were unclear. Officials in Amhara tended to adopt a strict
      interpretation that reflected fear of misuse and a deep concern for encouraging
      home birth (thus deviating from the clear national goal to increase facility
      based birth). Conversely, Oromiya officials framed policy in terms of the broader
      national goal to reduce maternal mortality, which allowed them to adopt multiple
      means of misoprostol distribution. DISCUSSION: The differences observed in
      regional practice likely stem from an ambiguously perceived national policy
      within a climate of decentralization that allowed for flexibility in local
      implementation. A policy that is clear, specific, evidence-based, and
      systematically communicated may facilitate common understanding of community
      based misoprostol for PPH prevention and, thus, increase women's access to this
      lifesaving intervention.

PMID- 24588921
TI  - Building district-level capacity for continuous improvement in maternal and
      newborn health.
AB  - INTRODUCTION: The Maternal and Newborn Health in Ethiopia Partnership (MaNHEP)
      adapted a collaborative improvement strategy to develop woreda (district)
      leadership capacity to support and facilitate continuous improvement of community
      maternal and neonatal health (CMNH) and to provide a model for other woredas,
      dubbed "lead" woredas. Community-level quality improvement (QI) teams tested
      solutions to improve CMNH care supported by monthly coaching and regular meetings
      to share experiences. This study examines the extent of the capacity built to
      support continuous improvement in CMNH care. METHODS: Surveys and in-depth
      interviews assessed the extent to which MaNHEP developed improvement capacity. A
      survey questionnaire evaluated woreda culture, leadership support, motivation,
      and capacity for improvement activities. Interviews focused on respondents'
      understanding and perceived value of the MaNHEP improvement approach. Bivariate
      analyses and multivariate linear regression models were used to analyze the
      survey data. Interview transcripts were organized by region, cadre, and key
      themes. RESULTS: Respondents reported significant positive changes in many areas
      of woreda culture and leadership, including involving a cross-section of
      community stakeholders (increased from 3.0 to 4.6 on 5-point Likert scale), using
      improvement data for decision making (2.8-4.4), using locally developed and
      tested solutions to improve CMNH care (2.5-4.3), demonstrating a commitment to
      improve the health of women and newborns (2.6-4.2), and creating a supportive
      environment for coaches and QI teams to improve CMNH (2.6-4.0). The mean scores
      for capacity were 3.7 and higher, reflecting respondents' agreement that they had
      gained capacity in improvement skills. Interview respondents universally
      recognized the capacity built in the woredas. The themes of community empowerment
      and focused improvement emerged strongly from the interviews. DISCUSSION: MaNHEP
      was able to build capacity for continuous improvement and develop lead woredas.
      The multifaceted approach to building capacity was critical for the success in
      creating lead woredas able to serve as models for other districts.

PMID- 24588922
TI  - Conspicuous visual signals do not coevolve with increased body size in marine sea
      slugs.
AB  - Many taxa use conspicuous colouration to attract mates, signal chemical defences
      (aposematism) or for thermoregulation. Conspicuousness is a key feature of
      aposematic signals, and experimental evidence suggests that predators avoid
      conspicuous prey more readily when they exhibit larger body size and/or pattern
      elements. Aposematic prey species may therefore evolve a larger body size due to
      predatory selection pressures, or alternatively, larger prey species may be more
      likely to evolve aposematic colouration. Therefore, a positive correlation
      between conspicuousness and body size should exist. Here, we investigated whether
      there was a phylogenetic correlation between the conspicuousness of animal
      patterns and body size using an intriguing, understudied model system to examine
      questions on the evolution of animal signals, namely nudibranchs (opisthobranch
      molluscs). We also used new ways to compare animal patterns quantitatively with
      their background habitat in terms of intensity variance and spatial frequency
      power spectra. In studies of aposematism, conspicuousness is usually quantified
      using the spectral contrast of animal colour patches against its background;
      however, other components of visual signals, such as pattern, luminance and
      spectral sensitivities of potential observers, are largely ignored. Contrary to
      our prediction, we found that the conspicuousness of body patterns in over 70
      nudibranch species decreased as body size increased, indicating that crypsis was
      not limited to a smaller body size. Therefore, alternative selective pressures on
      body size and development of colour patterns, other than those inflicted by
      visual hunting predators, may act more strongly on the evolution of aposematism
      in nudibranch molluscs. 

PMID- 24588923
TI  - Clinical guidelines for management of diabetes insipidus and syndrome of
      inappropriate antidiuretic hormone secretion after pituitary surgery.
AB  - Changes in water metabolism and regulation of vasopressin (AVP) or antidiuretic
      hormone (ADH) are common complications of pituitary surgery. The scarcity of
      studies comparing different treatment and monitoring strategies for these
      disorders and the lack of prior clinical guidelines makes it difficult to provide
      recommendations following a methodology based on grades of evidence. This study
      reviews the pathophysiology of diabetes insipidus and inappropriate ADH secretion
      after pituitary surgery, and is intended to serve as a guide for their diagnosis,
      differential diagnosis, treatment, and monitoring. 

PMID- 24588924
TI  - The Executive Interview (EXIT25) as a tool for assessing executive functioning in
      older medical and surgical inpatients referred to a psychiatry service:
      feasibility of creating a brief version.
AB  - BACKGROUND: Most neuropsychological tests of executive function are time
      consuming and otherwise unsuitable for routine bedside assessment, particularly
      in older people admitted to a general hospital. After introducing the Executive
      Interview (EXIT25) in our routine clinical practice, we hypothesized that it
      would be possible to shorten it for easier administration in our group of
      patients while maintaining or improving properties of the scale. METHODS: The
      EXIT25 was applied in 122 clinically stable medical and surgical inpatients aged
      65 years and over referred to the Liaison Psychiatry Service for Older People.
      Individual items were initially tested for floor and ceiling effects, inter-rater
      and test-retest reliability, and item-total correlations. Items were then
      selected for retention in the brief scale on the basis of adequate item-total
      correlation and inter-rater and test-retest reliability. The construct validity
      of the original and brief versions of the EXIT25 scale was assessed. RESULTS: The
      original EXIT25 scale was found to lack desirable scaling properties either as a
      classical or hierarchical scale. The study confirmed a possibility to reduce the
      number of items to nine out of the original 25 while improving internal
      consistency, test-retest and inter-rater reliability, and maintaining high
      correlation with the original EXIT25 score, and moderate inverse correlation with
      the Mini-Mental State Examination score. CONCLUSIONS: There is potential to
      abbreviate the original EXIT25, and improve internal consistency and hierarchical
      scaling properties. Future research is necessary to focus on piloting these brief
      measures of executive function in relevant clinical settings, when administered
      en bloc, rather than with items interspersed in the original longer version.

PMID- 24588925
TI  - Sulfur-doped polyimide photocatalyst with enhanced photocatalytic activity under
      visible light irradiation.
AB  - Sulfur-doped polyimide (SPI) photocatalysts were synthesized for the first time
      via an in situ thermal copolymerization method using sublimed sulfur (S4) as a
      dopant. Sulfur doping not only extended the absorption range of polyimide (PI)
      for visible light but also enhanced the oxidation ability of the photoinduced
      hole. The doped sulfur substitutes for the lattice nitrogen in triazine rings of
      PI to form the S-C bond and changes the distribution of negative charge in the
      two-dimensional plane of PI. The enhanced photocatalytic activity of SPI in the
      degradation of methyl orange is ascribed to the strong oxidation ability of the
      photoinduced hole of SPI and an effective suppression to the recombination of
      electrons and holes. 

PMID- 24588926
TI  - Disaster management among dental graduates in a private dental institution in
      India: a pilot study.
AB  - OBJECTIVE: To obtain insights into disaster management among dental graduates in
      a dental institute in India. METHODS: A total of 103 of 104 house surgeons in
      Shri Dharmasthala Manjunatheswar College of Dental Sciences and Hospital,
      Dharwad, participated in the main study (response rate = 99.04%). Their
      knowledge, attitude, and behavior regarding disaster management were assessed by
      use of a survey questionnaire. Information was also collected regarding age,
      gender, religion, and residence. RESULTS: Mean knowledge, attitude, and behavior
      scores toward disaster management were 45.46%, 79.53%, and 37.70%, respectively.
      A significant relationship was observed between knowledge and attitude scores (r
      = 0.248, P = .012). No significant differences were found in knowledge, attitude,
      and behavior by gender, religion, and residence. Religion was a significant
      predictor of knowledge scores (chi2 = 10.108, P = .006). CONCLUSIONS: Respondents
      had favorable attitudes toward disaster management, but their knowledge and
      behavior required considerable improvement. Knowledge of the respondents was
      significantly associated with their attitude. This pilot study highlights the
      need for curriculum changes in dental education in India and further nationwide
      study.

PMID- 24588927
TI  - Pre-emptive or preventive analgesia - lessons from the human literature?

PMID- 24588928
TI  - The immune response to anesthesia: part 1.
AB  - OBJECTIVE: To review the immune response to anesthesia including mechanical
      ventilation, inhaled anesthetic gases, and injectable anesthetics and sedatives.
      STUDY DESIGN: Review. METHODS AND DATABASES: Multiple literature searches were
      performed using PubMed and Google Scholar from spring 2012 through fall 2013.
      Relevant anesthetic and immune terms were used to search databases without year
      published or species constraints. The online database for Veterinary Anaesthesia
      and Analgesia and the Journal of Veterinary Emergency and Critical Care were
      searched by issue starting in 2000 for relevant articles. CONCLUSION: Recent
      research data indicate that commonly used volatile anesthetic agents, such as
      isoflurane and sevoflurane, may have a protective effect on vital organs. With
      the lung as the target organ, protection using an appropriate anesthetic protocol
      may be possible during direct pulmonary insults, including mechanical
      ventilation, and during systemic disease processes, such as endotoxemia,
      generalized sepsis, and ischemia-reperfusion injury.

PMID- 24588929
TI  - Prevalence and risk factors for canine post-anesthetic aspiration pneumonia (1999
      2009): a multicenter study.
AB  - OBJECTIVE: To determine the incidence of canine post-anesthetic aspiration
      pneumonia (AP) and to identify anesthetic agents, procedures and management
      factors associated with the development of AP. STUDY DESIGN: Multicenter,
      randomized, case-controlled retrospective study. ANIMALS: Two hundred and forty
      dogs affected with AP and 488 unaffected control dogs. METHODS: Electronic
      medical record databases at six Veterinary colleges were searched for dogs, coded
      for anesthesia or sedation and pneumonia from January 1999 to December 2009. The
      resultant 2158 records were hand-searched to determine eligibility for inclusion.
      Diagnosis of AP was made radiographically. Two unaffected control dogs were
      randomly selected for each affected dog, from a list of dogs that underwent
      sedation or anesthesia in the same time period and did not develop aspiration
      pneumonia. Fifty-seven factors were then evaluated for association with
      aspiration pneumonia. Data analysis was performed using univariate Chi-square or
      student t-tests, then multivariate logistic regression. RESULTS: Incidence of
      post-anesthetic AP was 0.17%, from 140,711 cases anesthetized or sedated over the
      10 year period. Two anesthesia-related events were significantly associated with
      development of AP: regurgitation and administration of hydromorphone at
      induction. Administration of anticholinergics was not associated with AP.
      Procedures associated with increased odds of aspiration pneumonia included
      laparotomy, upper airway surgery, neurosurgery, thoracotomy and endoscopy.
      Orthopedic surgery, ophthalmologic surgery, dental procedures, MRI, CT,
      bronchoscopy, cystoscopy, tracheoscopy and neutering were not associated with
      development of AP. Three patient factors were associated with the development of
      AP: megaesophagus, and a history of pre-existing respiratory or neurologic
      disease. Sixty-nine% of dogs with two or more of the above independent predictive
      variables developed AP. CONCLUSION AND CLINICAL RELEVANCE: Most anesthetic agents
      and procedures were not associated with the development of AP. We need to devise
      and evaluate strategies to protect at risk patients.

PMID- 24588930
TI  - Perianesthetic morbidity and mortality in dogs undergoing cervical and
      thoracolumbar spinal surgery.
AB  - OBJECTIVE: To evaluate and compare perioperative morbidity and mortality in dogs
      undergoing cervical and thoracolumbar spinal surgery. STUDY DESIGN: Prospective
      case series. ANIMALS: 157 dogs undergoing cervical or thoracolumbar spinal
      surgery. METHODS: Data were collected sequentially on canine cases presented from
      the Neurology Section of the North Carolina State University Veterinary Teaching
      Hospital for anesthesia and surgery for cervical spinal cord disease.
      Simultaneously, data were collected on all thoracolumbar spinal surgery cases
      during the same time period. Data included signalment, drugs administered,
      surgical approach, disease process, cardiac arrhythmias during anesthesia, and
      outcome. RESULTS: Data were collected from 164 surgical events in 157 dogs. There
      were 52 cervical approaches; four dorsal and 48 ventral. All thoracolumbar
      surgeries were approached dorsolaterally. Four dogs 4/52 (7.6%) undergoing a
      cervical approach did not survive to discharge. Two dogs (2/8; 25%) underwent
      atlanto-axial (AA) stabilization and suffered cardiovascular arrest and two dogs
      (2/38; 5.2%) undergoing cervical ventral slot procedures were euthanized
      following anesthesia and surgery due to signs of aspiration pneumonia. All dogs
      undergoing thoracolumbar surgery survived until discharge (112/112). Mortality in
      dogs undergoing cervical spinal surgery was greater compared with dogs undergoing
      thoracolumbar spinal surgery (p = 0.009), however, in dogs undergoing
      decompressive disc surgery, intraoperative death rates were not different between
      dogs undergoing a cervical compared with thoracolumbar approaches (p = 0.32) nor
      was there a significant difference in overall mortality (p = 0.07). CONCLUSION
      AND CLINICAL RELEVANCE: Overall, dogs undergoing cervical spinal surgery were
      less likely to survive until discharge compared with dogs undergoing
      thoracolumbar spinal surgery. Mortality in dogs undergoing cervical
      intervertebral disc decompression surgery was no different than for dogs
      undergoing thoracolumbar intervertebral disc decompression surgery. However, dogs
      undergoing cervical intervertebral disc decompression surgery should be
      considered at risk for aspiration pneumonia.

PMID- 24588932
TI  - Randomized clinical trial on the effect of a multispecies probiotic on
      visceroperception in hypersensitive IBS patients.
AB  - BACKGROUND: Irritable bowel syndrome (IBS) is characterized by heterogeneous
      pathophysiology and low response to treatment. Up to 60% of IBS patients suffers
      from visceral hypersensitivity, which is associated with symptom severity and
      underlying pathophysiological mechanisms. Recently, positive effects of
      probiotics in IBS have been reported, but overall the response was modest. We
      performed a study in IBS patients, characterized by visceral hypersensitivity
      measured with the rectal barostat, aiming to assess the effect of 6 weeks of
      multispecies probiotic mix on visceral pain perception. METHODS: We conducted a
      randomized, placebo-controlled, double-blind trial in forty Rome III IBS patients
      with visceral hypersensitivity. Prior to intake, patients kept a 2-week symptom
      diary and underwent a rectal barostat measurement. When hypersensitivity was
      confirmed, participation was allowed and patients received a multispecies
      probiotic with in vitro proven potential beneficial effects on mechanisms
      contributing to visceral hypersensitivity (six different probiotic strains; 10(9)
      cfu/g), or a placebo product of one sachet (5 g) per day for 6 weeks. At the end
      of the intervention period, visceroperception and symptoms were reassessed. KEY
      RESULTS: Thirty-five patients completed the trial. The percentage of patients
      with visceral hypersensitivity decreased significantly in the probiotic and
      placebo group (76.5% and 71.4%, respectively; N.S. between groups). Improvement
      in pain scores and mean symptom score did not differ between the probiotic and
      placebo group. CONCLUSIONS & INFERENCES: In this placebo-controlled trial in IBS
      patients with visceral hypersensitivity, no significant effect of a multispecies
      probiotic on viscerperception was observed. The study has been registered in the
      US National Library of Medicine (http://www.clinicaltrials.gov, NCT00702026).

PMID- 24588933
TI  - Stories and metaphors in the sensemaking of multiple primary health care
      organizational identities.
AB  - BACKGROUND: The Quebec primary health care delivery system has experienced
      numerous reforms over the last 15 years. In this study, we sought to examine how
      managers and primary care providers made sense of the creation of successive new
      primary care organizational forms. METHODS: We conducted a longitudinal
      qualitative case study in a primary care practice group located in Montreal,
      Quebec, for over 6 years (2002 to 2008). The data sources for the study include
      31 semi-structured interviews with key informants, in-situ observations of group
      meetings, as well as documents and field notes. Textual material was submitted to
      narrative and metaphor analysis. RESULTS: The core metaphor of the journey came
      from a set of stories in which the members of this primary care group depicted
      the processes undertaken towards developing a multidisciplinary cooperative
      practice, which include an uneasy departure, uncertainty about the destination,
      conflict among members who jump ship or stay on board, negotiations about the
      itinerary, and, finally, enduring challenges in leading the way and being
      pioneers of change in the organization of primary care in their institutional
      context. Identification with the initial family medicine unit identity was
      persistent over time, but successive reforms further enriched its meaning as it
      became a multidisciplinary primary care practice pioneering organizational
      change. CONCLUSIONS: In order to support primary care reforms in complex
      institutional fields, this study proposes that decision-makers undertake a
      journey in which they recognize both the need to capitalize on existing
      meaningful and legitimated organizational identities, as well as the necessity
      for collective leadership in the management of multiple organizational identities
      over time.

PMID- 24588934
TI  - New properties of wheat bran: anti-biofilm activity and interference with
      bacteria quorum-sensing systems.
AB  - Some plant extracts, have been demonstrated to interfere with the microbial
      metabolism of several pathogenic bacteria. Within this antimicrobial properties
      it has been described the potential to inhibit or destroy biofilms or to
      interfere in quorum-sensing (QS) systems. However, to our knowledge, no study
      exploring this potential of wheat-bran (WB) has been published. The purpose of
      the present study is to evaluate the anti-biofilm activity of WB against a cow
      mastitis strain of Staphylococcus aureus and also its possible interference with
      bacterial QS systems. The potential of inhibition and destruction of the biofilm
      was studied by different in vitro assays. Also, we tested the ability of WB to
      interfere in bacterial QS by degrading acyl-homoserine lactones (AHL) as one of
      the most studied QS signal molecules for Gram-negative bacteria. The soluble
      extract of WB at 0.5% showed anti-biofilm activity, inhibiting biofilm formation
      and also destroying it. Similarly, the > 300 kDa fraction from WB had significant
      anti-biofilm activity in both in vitro assays. The WB also showed a potential to
      interfere with bacterial QS systems, as it was demonstrated to contain certain
      lactonase activity able to reduce AHL concentration in the medium. The present
      study reveals two additional beneficial properties of WB extract never explored
      before, which may be related to the presence of defence compounds in the plant
      extract able to interfere with microbial biofilms and also QS systems. 

PMID- 24588935
TI  - Weak protein-ligand interactions studied by small-angle X-ray scattering.
AB  - Small-angle X-ray scattering (SAXS) is a powerful technique for studying weak
      interactions between proteins and their ligands (other proteins, DNA/RNA or small
      molecules) in solution. SAXS provides knowledge about the equilibrium state, the
      stoichiometry of binding and association-dissociation processes. The measurements
      are conducted in a solution environment that allows easy monitoring of
      modifications in protein-ligand association state upon environmental changes.
      Model-free parameters such as the molecular mass of a system and the radius of
      gyration can be obtained directly from the SAXS data and give indications about
      the association state. SAXS is also widely employed to build models of biological
      assemblies at a resolution of approximately 10-20 A. Low-resolution shapes can be
      generated ab initio, although more detailed and biologically interpretable
      information can be obtained by hybrid modelling. In the latter approach,
      composite structures of protein-ligand complexes are constructed using atomic
      models of individual molecules. These may be predicted homology models or
      experimental structures from X-ray crystallography or NMR. This review focuses on
      using SAXS data to model structures of protein-ligand complexes and to study
      their dynamics. The combination of SAXS with other methods such as size exclusion
      chromatography and dynamic light scattering is discussed. 

PMID- 24588937
TI  - Successful treatment with 532-nm Q-switched Nd:YAG laser of cutaneous siderosis
      following intravenous iron extravasation.

PMID- 24588936
TI  - Pegloticase immunogenicity: the relationship between efficacy and antibody
      development in patients treated for refractory chronic gout.
AB  - INTRODUCTION: The efficacy of pegloticase, a polyethylene glycol (PEG)-conjugated
      mammalian recombinant uricase, approved for chronic refractory gout, can be
      limited by the development of antibodies (Ab). Analyses from 2 replicate, 6
      month, randomized controlled trials were performed to characterize Ab responses
      to pegloticase. METHODS: Anti-pegloticase, anti-PEG, and anti-uricase Ab were
      determined by validated enzyme-linked immunosorbent assays. Ab titers were
      analyzed for possible relationships with serum pegloticase concentrations, serum
      uric acid (sUA) lowering, and risk of infusion reactions (IRs). RESULTS: Sixty
      nine (41%) of 169 patients receiving pegloticase developed high titer anti
      pegloticase Ab (> 1:2430) and 40% (67/169) developed anti-PEG Ab; 1 patient
      receiving placebo developed high titer anti-pegloticase Ab. Only 14% (24/169) of
      patients developed anti-uricase Ab, usually at low titer. In responders, patients
      showing sustained UA lowering, mean anti-pegloticase titers at week 25 (1:837 +/-
      1687 with biweekly and 1:2025 +/- 4506 with monthly dosing) were markedly lower
      than in nonresponders (1:34,528 +/- 42,228 and 1:89,658 +/- 297,797,
      respectively). Nonresponder status was associated with reduced serum pegloticase
      concentrations. Baseline anti-pegloticase Ab, evident in 15% (31/212) of
      patients, did not predict subsequent loss of urate-lowering response. Loss of sUA
      response preceded IRs in 44 of 56 (79%) pegloticase-treated patients.
      CONCLUSIONS: Loss of responsiveness to pegloticase is associated with the
      development of high titer anti-pegloticase Ab that increase clearance of
      pegloticase and are associated with a loss of the sUA lowering effect and
      increased IR risk. Pre-infusion sUA can be used as a surrogate for the presence
      of deleterious anti-pegloticase Ab. TRIAL REGISTRATION: NCT00325195. Registered
      10 May 2006, NCT01356498. Registered 27 October 2008.

PMID- 24588939
TI  - Being drunk and high during sex is not associated with condom use behaviours: a
      study of high-risk young Black males.
AB  - Objective To assess the relationship between the frequency of being drunk and
      high during sex, and condom use errors and problems (CUEP) among a sample of high
      risk young Black males recruited from the United States. METHODS: Data were
      collected in clinics treating sexually transmissible infections in three cities
      in the southern United States. Males 15-23 years of age (n=697) who identified as
      African-American and reported recent (past 2 months) condom use were eligible.
      Measures of alcohol and drug use, as well as condom use behaviours were assessed
      by audio-computer assisted self-interview. Eighteen CUEP were included in this
      assessment. RESULTS: Sixteen bivariate correlations were obtained. The magnitude
      of the coefficients was small, ranging from 0.01 to 0.13. Only three were
      significant. These were positive associations between the frequency of being
      drunk and the frequency of unprotected vaginal sex, as well as the frequency of
      the 18-item measure of CUEP. A significant correlation was also found between the
      frequency of being high during sex and the frequency of unprotected vaginal sex.
      Adjustments for age did not change the findings. CONCLUSIONS: Interventions
      designed to promote safer sex behaviours among young Black males attending
      sexually transmissible infection clinics are no more likely to benefit patients
      through the inclusion of messages and training attempting to dissuade the use of
      alcohol and drugs before or during sex.

PMID- 24588938
TI  - Tea consumption didn't modify the risk of fracture: a dose-response meta-analysis
      of observational studies.
AB  - BACKGROUND: Fractures are important causes of healthy damage and economic loss
      nowadays. The conclusions of observational studies on tea consumption and
      fracture risk are still inconsistent. The objective of this meta-analysis is to
      determine the effect of tea drinking on the risk of fractures. METHODS: A
      comprehensive literature search was conducted in PubMed, Embase and reference
      lists of the relevant articles. Observational studies that reported an estimate
      of the association between tea drinking and incidence of fractures were included.
      A meta-analysis was conducted by the STATA software. RESULTS: A total of 9
      studies involving 147,950 individuals that examined the association between tea
      consumption and risk of fractures were included in this meta-analysis. The odds
      risks (ORs) with 95% confidence intervals (CIs) were pooled using a random
      effects model. The pooled OR of 9 observational studies for the tea consumption
      on risk of fracture was 0.89 (95% CI, 0.78-1.04). In the subgroup analyses, no
      significant association was detected in neither cohort studies (n=3; OR, 0.97;
      95% CI, 0.89-1.06) nor case-control studies (n=6; OR, 0.91; 95% CI, 0.70-1.19),
      respectively. No significant association was detected in the dose-response meta
      analysis. CONCLUSIONS: Tea consumption might not be associated with the risk of
      fractures. The following large-sample and well-designed studies are required to
      confirm the existing conclusions. VIRTUAL SLIDES: The virtual slide(s) for this
      article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/5309904231178427.

PMID- 24588940
TI  - The role of total fats, saturated/unsaturated fatty acids and cholesterol content
      in chicken meat as cardiovascular risk factors.
AB  - BACKGROUND: The objective of the study was to present information about the
      chemical composition, the fatty acids profile, and cholesterol content of chicken
      meat in order to investigate the impact of chicken meat consumption on
      cardiovascular risk in the general population. METHODS: A total of 48 6-wk-old
      broiler chickens broilers from two farms in June to November of 2012, and
      February of 2013, were used in this trial. Total lipid content was determined by
      extraction of fat by petrol ether (Soxhlet) after acid hydrolysis of samples.
      Fatty acids were determined by capillary gas chromatography. Cholesterol
      determination was performed by using HPLC/PDA system. RESULTS: The results
      indicate that the total free cholesterol content in raw breast and drumstick of
      chickens was in the range of 37,41-79,9 mg/100 g and 48,35-99,5 mg/100 g,
      respectively. The main fatty acids identified in all cuts were C18:1c9, C18:2n6,
      C16:0, C18:0, and C16:1. Decreasing the dietary n-6/n-3 clearly decreased the
      content in breast and drumstick muscle of C18:2n6, C18:3n3, and C20: 3n6, but
      increased that of C16:0, C18:0, and C20:2. Also, the major saturated fatty acid
      (SFA) (C16:0 and C18:0) was significantly differ among the four treatments.
      CONCLUSION: Our study shows that dietary fat and fatty acid composition influence
      the concentrations of total cholesterol content, total fat content, and fatty
      acid composition in broiler muscle. This information will aid in determining the
      burden of chicken meat as a cardiovascular risk factors disease and act as a
      planning tool for public-health Programmes.

PMID- 24588941
TI  - Retinopathy among young adults with Diabetes Mellitus from a tertiary care
      setting in Sri Lanka.
AB  - BACKGROUND: Diabetic retinopathy (DR) is one of the leading causes for complete
      loss of vision among working-aged adults around the world. The present study aims
      to evaluate the rate of DR and its risk factors among the adults with young-onset
      diabetes from a tertiary care setting in Sri Lanka. METHODS: A consecutive sample
      of 1,007 individuals referred from multiple centers, were invited for the study.
      Ophthalmological evaluation was done, with dilated indirect ophthalmoscopy by an
      Ophthalmologist. Retinopathy was classified according to the International
      Clinical DR Disease Severity Scale. An interviewer-administered questionnaire was
      used to collect socio-demographic and anthropometric details. Seated blood
      pressure, Fasting Blood Glucose (FBG), HbA1c and urine microalbumin were also
      measured. Data were analysed using SPSSv14. A binary logistic regression analysis
      was performed in all patients, with 'presence of DR' as the dichotomous dependent
      variable and other independent covariates. RESULTS: Sample size was 684 (response
      rate-67.9%), mean age was 37.1 +/- 5.9 years and 36.0% were males. Mean duration
      of diabetes was 5.2 +/- 4.0 years. Previous retinal screening had been done in
      51.0% by a non-specialist doctor and in 41.5% by a consultant ophthalmologist.
      Rate of any degree of DR in the study population was 18.1% (Males 16.4%, Females
      20.0%; P = NS). In patients with DR, majority had mild Non-Proliferative DR
      (NPDR) (57.2%), while 32.2% had moderate NPDR, 0.8% had severe NPDR and 9.7% had
      maculopathy. Mean age, duration of diabetes, systolic (SBP) and diastolic blood
      pressure (DBP), FBG, HbA1c and urine microalbumin levels were significantly
      higher amongst the patients with DR. The results of the binary logistic
      regression indicate that the duration of diabetes (OR:1.24), HbA1c (OR:1.19), age
      (OR:1.11), urine Microalbumin (OR:1.11) and DBP (OR:1.04) all were significantly
      associated with DR. CONCLUSIONS: In this large multi center study, nearly one in
      five adults with young-onset diabetes was found to have retinopathy. Age,
      duration of diabetes, HbA1C and urine Microalbumin levels were significantly
      associated with the presence of retinopathy, while HbA1c was also a significant
      factor determining severity. Nearly 50% of the study population has never
      undergone retinal screening by an ophthalmologist, highlighting the need for well
      organized screening programs.

PMID- 24588942
TI  - Novel visualised three-dimensional images are useful for treating coronary artery
      fistulas in infants.
AB  - Here we report an infant with coronary artery fistulas. To clearly visualise the
      fistulas and surrounding materials, we utilised three-dimensional computed
      tomography, and the images were transferred as novel visualised three-dimensional
      images using a reconstruction technique. With the images, we could repair the
      fistulas accurately. We believe that these images are useful for repairing
      coronary artery fistulas in infants. 

PMID- 24588944
TI  - Inhibitory effect of Bcl-xL gene on toxicity induced by sodium nitroprusside in
      SH-SY5Y cells.

PMID- 24588946
TI  - Cultural correlates of burden in primary caregivers of older relatives: a cross
      sectional study.
AB  - PURPOSE: To analyze the effect of cultural factors on the subjective burden of
      primary home caregivers of older relatives. DESIGN: Cross-sectional study.
      Primary home caregivers (N = 208) of older relatives were recruited in Spain
      using systematic random sampling. METHODS: The data were collected in 2010
      through interviews. The measures included sociodemographic characteristics,
      stressors (the intensity of care provided and the care-recipient's needs; the
      latter were assessed using the Barthel Index, the Pfeiffer Short Portable Mental
      Status Questionnaire and the Cummings Neuropsychiatric Inventory), cultural
      factors (kinship ties, common residence, perceived social support, and cultural
      motives for caregiving), and caregiver subjective burden (Caregiver Strain
      Index). The data were analyzed using bivariate procedures and multiple linear
      regression. FINDINGS: After controlling for caregiver age, caregiver gender,
      stressors, and duration of caregiving, subjective burden was negatively
      associated with perceived social support and reciprocity, and in the subgroup of
      adult children, it was positively associated with common residence. Cultural
      factors explained 29% of the variance in burden. CONCLUSIONS: Our findings add to
      the existing evidence regarding the influence of cultural factors in the
      perception of burden in caregiving situations. CLINICAL RELEVANCE: A risk profile
      could be proposed for subjective burden in primary family caregivers. Individuals
      who are at risk are characterized as young, offspring who live with the care
      recipient, care for a care recipient with behavioral problems, are unsatisfied
      with the social support received, and have a low balanced reciprocity.

PMID- 24588947
TI  - Where do editorials come from?

PMID- 24588943
TI  - Chronic prenatal stress epigenetically modifies spinal cord BDNF expression to
      induce sex-specific visceral hypersensitivity in offspring.
AB  - BACKGROUND: Irritable bowel syndrome (IBS) is a heterogeneous disorder with
      abdominal pain as one of the primary symptoms. The etiology of IBS remains
      unknown. Epidemiological studies found that a subset of these patients have a
      history of adverse early-life experiences. We tested the hypothesis that chronic
      prenatal stress (CPS) epigenetically enhances brain-derived neurotrophic factor
      (BDNF) in spinal cord to aggravate colon sensitivity to colorectal distension
      (CRD) differentially in male and female offspring. METHODS: We used heterotypic
      intermittent chronic stress (HeICS) protocols in pregnant dams from E11 until
      delivery. KEY RESULTS: Chronic prenatal stress induced significant visceral
      hypersensitivity (VHS) to CRD in male and female offspring. A second exposure to
      HeICS in adult offspring exacerbated VHS greater in female offspring that
      persisted longer than in male offspring. Chronic prenatal stress upregulated BDNF
      expression in the lumbar-sacral dorsal horn that correlated with the exacerbation
      of VHS in female, but not in male offspring. The upregulation of BDNF was due to
      a significant increase in RNA Pol II binding, histone H3 acetylation, and
      significant decrease in histone deacetylase 1 association with the core promoter
      of BDNF in female offspring. Other chronic prenatal and neonatal stress protocols
      were less effective than HeICS. CONCLUSIONS & INFERENCES: The development of VHS,
      which contributes to the symptom of intermittent abdominal pain, is a two-step
      process, chronic in utero stress followed by chronic stress in adult-life. This
      two-step process induces aggravated and persistent colon hypersensitivity in
      female than in male offspring. Our preclinical model explains several clinical
      features in IBS patients.

PMID- 24588949
TI  - Scientific criticism in homoeopathy: need to test more than disputes.

PMID- 24588945
TI  - Glutathione S-transferase L1 multiplex serology as a measure of cumulative
      infection with human papillomavirus.
AB  - BACKGROUND: Several assays are used to measure type-specific serological
      responses to human papillomavirus (HPV), including the bead-based glutathione S
      transferase (GST)-L1 multiplex serology assay and virus-like particle (VLP)-based
      ELISA. We evaluated the high-throughput GST-L1, which is increasingly used in
      epidemiologic research, as a measure of cumulative HPV infection and future
      immune protection among HPV-unvaccinated women. METHODS: We tested enrollment
      sera from participants in the control arm of the Costa Rica Vaccine Trial (n =
      488) for HPV16 and HPV18 using GST-L1, VLP-ELISA, and two assays that measure
      neutralizing antibodies (cLIA and SEAP-NA). With statistical adjustment for
      sampling, we compared GST-L1 serostatus to established HPV seropositivity
      correlates and incident cervical HPV infection using odds ratios. We further
      compared GST-L1 to VLP-ELISA using pair-wise agreement statistics and by defining
      alternate assay cutoffs. RESULTS: Odds of HPV16 GST-L1 seropositivity increased
      with enrollment age (OR = 1.20 per year, 95%CI 1.03-1.40) and lifetime number of
      sexual partners (OR = 2.06 per partner, 95%CI 1.49-2.83), with similar results
      for HPV18. GST-L1 seropositivity did not indicate protection from incident
      infection over 4 years of follow-up (HPV16 adjusted OR = 1.72, 95%CI 0.95-3.13;
      HPV18 adjusted OR = 0.38, 95%CI 0.12-1.23). Seroprevalence by GST-L1 (HPV16 and
      HPV18, respectively) was 5.0% and 5.2%, compared to 19.4% and 23.8% by VLP-ELISA,
      giving positive agreement of 39.2% and 20.8%. Lowering GST-L1 seropositivity
      cutoffs improved GST-L1/VLP-ELISA positive agreement to 68.6% (HPV16) and 61.5%
      (HPV18). CONCLUSIONS: Our data support GST-L1 as a marker of cumulative HPV
      infection, but not immune protection. At lower seropositivity cutoffs, GST-L1
      better approximates VLP-ELISA.

PMID- 24588948
TI  - The EVOLVE study is negative, so what does this 'bitter pill' of disappointment
      mean now for renal patients?
AB  - The extremely high morbidity and mortality experienced by subjects with chronic
      kidney disease (CKD) has often been described and reviewed, but this familiarity
      should not breed indifference to the huge burden of premature cardiovascular
      disease - something which becomes more obvious, but increasingly challenging to
      treat, as GFR declines, or proteinuria increases. The health outcomes for a
      middle-aged person entering renal replacement therapy are as bad as those seen
      with a major solid organ malignancy; while there has been modest progress in
      improving outcomes over the last two decades, the diagnosis of significant or
      progressive CKD should and thus still does continue to cast a shadow over
      patients, carers and healthcare professionals alike.

PMID- 24588950
TI  - Short-term mortality in acute coronary syndrome: effect of dysglycaemia and
      smoking.

PMID- 24588951
TI  - The complexity of managing an ageing population.

PMID- 24588952
TI  - Response to McElwaine and Robinson.

PMID- 24588953
TI  - [Colloquium Adelf-Emois "Hospital information system and epidemiology". Paris, 3
      4 April 2014. Foreword].

PMID- 24588954
TI  - Novel self-expandable, stent-based transcatheter pulmonic valve: a preclinical
      animal study.
AB  - BACKGROUND: Because transcatheter implantation of pulmonary valve is indicated
      for limited-size dysfunctional right ventricular outflow tract only as a balloon
      expandable stent, we investigated the feasibility of a large-diameter self
      expandable valved stent and the durability of the valve after >6 months. METHODS:
      We made a nitinol-wire-based, self-expandable valved stent with leaflets made
      from porcine pericardium. The porcine pericardium was treated with alpha
      galactosidase, glutaraldehyde, and glycine after decellularization. After cutting
      the inguinal or cervical area, we implanted a valved stent in 12 sheep through
      the femoral or jugular vein by using an 18-Fr delivery catheter, controlling the
      catheter handles and hook block under fluoroscopic and echocardiographic
      guidance. RESULTS: The mean body weight of sheep was 43.9 kg. We successfully
      implanted valved stents (diameter: 24 mm in 7 sheep, 26 mm in 5 sheep) in good
      position in 8 sheep, in the main pulmonary artery (PA) in 2 sheep, and in the
      right ventricular outlet tract (RVOT) in 2 sheep. We sacrificed 8 sheep (6 sheep
      in good position, 1 sheep in the main PA, and 1 sheep in the RVOT) after >6
      months. Five of the 6 sheep implanted in good position showed well-preserved
      valve morphology at the time of sacrifice. Histologic findings after routine
      sacrifice showed well-maintained collagen wave structure and no visible
      calcification in all explanted valve leaflets. CONCLUSIONS: Transcatheter
      implantation of a nitinol-wire-based, self-expandable valved stent in the
      pulmonic valve was feasible, and stents implanted in good position showed well
      preserved valve leaflets with functional competence in the mid-term results.

PMID- 24588955
TI  - Dressings as an adjunct to pressure ulcer prevention: consensus panel
      recommendations.
AB  - The formulation of recommendations on the use of wound dressings in pressure
      ulcer prevention was undertaken by a group of experts in pressure ulcer
      prevention and treatment from Australia, Portugal, UK and USA. After review of
      literature, they concluded that there is adequate evidence to recommend the use
      of five-layer silicone bordered dressings (Mepilex Border Sacrum((r)) and 3 layer
      Mepilex Heel((r)) dressings by Molnlycke Health Care, Gothenburg, Sweden) for
      pressure ulcer prevention in the sacrum, buttocks and heels in high-risk
      patients, those in Emergency Department (ED), intensive care unit (ICU) and
      operating room (OR). Literature on which this recommendation is based includes
      one prospective randomised control trial, three cohort studies and two case
      series. Recommendations for dressing use in patients at high risk for pressure
      injury and shear injury were also provided. 

PMID- 24588956
TI  - Effects of humidity on foil and vial packaging to preserve glucose and lactate
      test strips for disaster readiness.
AB  - OBJECTIVE: Efficient emergency and disaster response is challenged by
      environmental conditions exceeding test reagent storage and operating
      specifications. We assessed the effectiveness of vial and foil packaging in
      preserving point-of-care (POC) glucose and lactate test strip performance in
      humid conditions. METHODS: Glucose and lactate test strips in both packaging were
      exposed to mean relative humidity of 97.0 +/- 1.1% in an environmental chamber
      for up to 168 hours. At defined time points, stressed strips were removed and
      tested in pairs with unstressed strips using whole blood samples spiked to
      glucose concentrations of 60, 100, and 250 mg/dL (n = 20 paired measurements per
      level). A Wilcoxon signed rank test was used to compare stressed and unstressed
      test strip measurements. RESULTS: Stressed glucose and lactate test strip
      measurements differed significantly from unstressed strips, and were inconsistent
      between experimental trials. Median glucose paired difference was as high as 12.5
      mg/dL at the high glucose test concentration. Median lactate bias was -0.2
      mmol/L. Stressed strips from vial (3) and foil (7) packaging failed to produce
      results. CONCLUSIONS: Both packaging designs appeared to protect glucose and
      lactate test strips for at least 1 week of high humidity stress. Documented strip
      failures revealed the need for improved manufacturing process.

PMID- 24588957
TI  - [Rasburicase-induced methemoglobinemia in a patient with leukemia recurrence].

PMID- 24588958
TI  - [Late-onset Group B Streptococcus disease in twins delivered by caesarean
      section].
AB  - Group B Streptococcus (GBS) is a commensal pathogen of the gut microflora with a
      well-established role in the aetiology of early and late onset GBS infections in
      the newborn. The incidence of early onset infections by vertical transmission has
      been drastically reduced in recent decades with the use of intravenous
      intrapartum prophylaxis. Progress in risk factor detection and prophylaxis of
      late-onset infection has however remained static. The ongoing modifications and
      improvements of the guidelines regarding prophylaxis, risk factors and prevention
      of the early-onset GBS disease have not addressed late-onset GBS infection in
      detail. The following cases illustrate the presence of grey areas in current
      guidelines and in the knowledge of the pathogenesis of late-onset disease. 

PMID- 24588960
TI  - A novel anti-windup framework for cascade control systems: an application to
      underactuated mechanical systems.
AB  - This paper describes the anti-windup compensator (AWC) design methodologies for
      stable and unstable cascade plants with cascade controllers facing actuator
      saturation. Two novel full-order decoupling AWC architectures, based on
      equivalence of the overall closed-loop system, are developed to deal with windup
      effects. The decoupled architectures have been developed, to formulate the AWC
      synthesis problem, by assuring equivalence of the coupled and the decoupled
      architectures, instead of using an analogy, for cascade control systems. A
      comparison of both AWC architectures from application point of view is provided
      to consolidate their utilities. Mainly, one of the architecture is better in
      terms of computational complexity for implementation, while the other is suitable
      for unstable cascade systems. On the basis of the architectures for cascade
      systems facing stability and performance degradation problems in the event of
      actuator saturation, the global AWC design methodologies utilizing linear matrix
      inequalities (LMIs) are developed. These LMIs are synthesized by application of
      the Lyapunov theory, the global sector condition and the L2 gain reduction of the
      uncertain decoupled nonlinear component of the decoupled architecture. Further,
      an LMI-based local AWC design methodology is derived by utilizing a local sector
      condition by means of a quadratic Lyapunov function to resolve the windup problem
      for unstable cascade plants under saturation. To demonstrate effectiveness of the
      proposed AWC schemes, an underactuated mechanical system, the ball-and-beam
      system, is considered, and details of the simulation and practical implementation
      results are described. 

PMID- 24588959
TI  - Analysis of BRAF(V600E) mutation and DNA methylation improves the diagnostics of
      thyroid fine needle aspiration biopsies.
AB  - BACKGROUND: Thyroid nodules with indeterminate cytological features on fine
      needle aspiration biopsy specimens (FNABs) have a ~20% risk of thyroid cancer.
      BRAF(V600E) mutation and DNA methylation are useful markers to distinguish
      malignant thyroid neoplasm from benign. The aim of this study was to determine
      whether combined detection of BRAF(V600E) mutation and methylation markers on
      FNABs could improve the diagnostic accuracy of thyroid cancer. METHODS: Using
      pyrosequencing and quantitative methylation-specific PCR (Q-MSP) methods, FNABs
      from 79 and 38 patients with thyroid nodules in training and test groups,
      respectively, were analyzed for BRAF(V600E) mutation and gene methylation.
      RESULTS: BRAF(V600E) mutation was found in 30/42 (71.4%) and 14/20 (70%) FNABs in
      training and test groups, respectively. All BRAF(V600E)-positive samples were
      histologically diagnosed as papillary thyroid cancer (PTC) after thyroidectomy.
      As expected, BRAF mutation was not found in all benign nodules. Moreover, we
      demonstrated that the five genes, including CALCA, DAPK1, TIMP3, RAR-beta and
      RASSF1A, were aberrantly methylated in FNABs. Of them, methylation level of DAPK1
      in PTCs was significantly higher than that in benign samples (P <0.0001).
      Conversely, methylation level of RASSF1A in PTCs was significantly lower than
      that in benign samples (P =0.003). Notably, compared with BRAF mutation testing
      alone, combined detection of BRAF mutation and methylation markers increased the
      diagnostic sensitivity and accuracy of PTC with excellent specificity.
      CONCLUSION: Our data have demonstrated that combine analysis of BRAF mutation and
      DNA methylation markers on FNABs may be a useful strategy to facilitate the
      diagnosis of malignant thyroid neoplasm, particularly PTC. VIRTUAL SLIDES: The
      virtual slide(s) for this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/6080878071149177.

PMID- 24588961
TI  - Design and synthesis of conformationally restricted inhibitors of active thrombin
      activatable fibrinolysis inhibitor (TAFIa).
AB  - A series of 4,5,6,7-tetrahydro-1H-benzimidazole-5-carboxylic acid and 5,6,7,8
      tetrahydroimidazo[1,2-a]pyridine-7-carboxylic acid derivatives designed as
      inhibitors of TAFIa has been prepared via a common hydrogenation-alkylation
      sequence starting from the appropriate benzimidazole and imidazopyridine system.
      We present a successful design strategy using a conformational restriction
      approach resulting in potent and selective inhibitors of TAFIa. The X-ray
      structure of compound 5 in complex with a H333Y/H335Q double mutant TAFI indicate
      that the conformational restriction is responsible for the observed potency
      increase. 

PMID- 24588962
TI  - The identification of novel 5'-amino gemcitabine analogs as potent RRM1
      inhibitors.
AB  - The ribonucleotide reductase (RNR) enzyme is a heteromer of RRM1 and RRM2
      subunits. The active enzyme catalyzes de novo reduction of ribonucleotides to
      generate deoxyribonucleotides (dNTPs), which are required for DNA replication and
      DNA repair processes. Complexity in the generation of physiologically relevant,
      active RRM1/RRM2 heterodimers was perceived as limiting to the identification of
      selective RRM1 inhibitors by high-throughput screening of compound libraries and
      led us to seek alternative methods to identify lead series. In short, we found
      that gemcitabine, as its diphosphate metabolite, represents one of the few
      described active site inhibitors of RRM1. We herein describe the identification
      of novel 5'-amino gemcitabine analogs as potent RRM1 inhibitors through in-cell
      phenotypic screening. 

PMID- 24588964
TI  - Relations of serum soluble E-selectin and adiponectin with enlarged perivascular
      spaces in patients with recent lacunar infarction.

PMID- 24588963
TI  - Discovery of 3-(4-methanesulfonylphenoxy)-N-[1-(2-methoxy-ethoxymethyl)-1H
      pyrazol-3-yl]-5-(3-methylpyridin-2-yl)-benzamide as a novel glucokinase activator
      (GKA) for the treatment of type 2 diabetes mellitus.
AB  - Novel heteroaryl-containing benzamide derivatives were synthesized and screened
      using an in vitro assay measuring increases in glucose uptake and glucokinase
      activity stimulated by 10mM glucose in rat hepatocytes. From a library of
      synthesized compounds, 3-(4-methanesulfonylphenoxy)-N-[1-(2-methoxy-ethoxymethyl)
      1H-pyrazol-3-yl]-5-(3-methyl pyridin-2-yl)-benzamide (19e) was identified as a
      potent glucokinase activator with assays demonstrating an EC50 of 315nM and the
      induction of a 2.23 fold increase in glucose uptake. Compound 19e exhibited a
      glucose AUC reduction of 32% (50mg/kg) in an OGTT study with C57BL/6J mice
      compared to 28% for metformin (300mg/kg). Single treatment of the compound in
      C57BL/J6 and ob/ob mice elicited basal glucose lowering activity, while in a two
      week repeated dose study with ob/ob mice, the compound significantly decreased
      blood glucose levels with no evidence of hypoglycemia risk. In addition, 19e
      exhibited favorable pharmacokinetic parameters in mice and rats and excellent
      safety margins in liver and testicular toxicity studies. Compound 19e was
      therefore selected as a development candidate for the potential treatment of type
      2 diabetes. 

PMID- 24588965
TI  - The brain-enriched microRNA miR-124 in plasma predicts neurological outcome after
      cardiac arrest.
AB  - INTRODUCTION: Early prognostication after successful cardiopulmonary
      resuscitation is difficult, and there is a need for novel methods to estimate the
      extent of brain injury and predict outcome. In this study, we evaluated the
      impact of the cardiac arrest syndrome on the plasma levels of selected tissue
      specific microRNAs (miRNAs) and assessed their ability to prognosticate death and
      neurological disability. METHODS: We included 65 patients treated with
      hypothermia after cardiac arrest in the study. Blood samples were obtained at 24
      hours and at 48 hours. For miRNA-screening purposes, custom quantitative
      polymerase chain reaction (qPCR) panels were first used. Thereafter individual
      miRNAs were assessed at 48 hours with qPCR. miRNAs that successfully predicted
      prognosis at 48 hours were further analysed at 24 hours. Outcomes were measured
      according to the Cerebral Performance Category (CPC) score at 6 months after
      cardiac arrest and stratified into good (CPC score 1 or 2) or poor (CPC scores 3
      to 5). RESULTS: At 48 hours, miR-146a, miR-122, miR-208b, miR-21, miR-9 and miR
      128 did not differ between the good and poor neurological outcome groups. In
      contrast, miR-124 was significantly elevated in patients with poor outcomes
      compared with those with favourable outcomes (P < 0.0001) at 24 hours and 48
      hours after cardiac arrest. Analysis of receiver operating characteristic curves
      at 24 and 48 hours after cardiac arrest showed areas under the curve of 0.87 (95%
      confidence interval (CI) = 0.79 to 0.96) and 0.89 (95% CI = 0.80 to 0.97),
      respectively. CONCLUSIONS: The brain-enriched miRNA miR-124 is a promising novel
      biomarker for prediction of neurological prognosis following cardiac arrest.

PMID- 24588967
TI  - Protein leverage and energy intake.
AB  - Increased energy intakes are contributing to overweight and obesity. Growing
      evidence supports the role of protein appetite in driving excess intake when
      dietary protein is diluted (the protein leverage hypothesis). Understanding the
      interactions between dietary macronutrient balance and nutrient-specific appetite
      systems will be required for designing dietary interventions that work with,
      rather than against, basic regulatory physiology. Data were collected from 38
      published experimental trials measuring ad libitum intake in subjects confined to
      menus differing in macronutrient composition. Collectively, these trials
      encompassed considerable variation in percent protein (spanning 8-54% of total
      energy), carbohydrate (1.6-72%) and fat (11-66%). The data provide an opportunity
      to describe the individual and interactive effects of dietary protein,
      carbohydrate and fat on the control of total energy intake. Percent dietary
      protein was negatively associated with total energy intake (F = 6.9, P < 0.0001)
      irrespective of whether carbohydrate (F = 0, P = 0.7) or fat (F = 0, P = 0.5)
      were the diluents of protein. The analysis strongly supports a role for protein
      leverage in lean, overweight and obese humans. A better appreciation of the
      targets and regulatory priorities for protein, carbohydrate and fat intake will
      inform the design of effective and health-promoting weight loss diets, food
      labelling policies, food production systems and regulatory frameworks. 

PMID- 24588968
TI  - Barbie.

PMID- 24588966
TI  - Which type of sedentary behaviour intervention is more effective at reducing body
      mass index in children? A meta-analytic review.
AB  - Sedentary behaviour is emerging as an independent risk factor for paediatric
      obesity. Some evidence suggests that limiting sedentary behaviour alone could be
      effective in reducing body mass index (BMI) in children. However, whether adding
      physical activity and diet-focused components to sedentary behaviour reduction
      interventions could lead to an additive effect is unclear. This meta-analysis
      aims to assess the overall effect size of sedentary behaviour interventions on
      BMI reduction and to compare whether interventions that have multiple components
      (sedentary behaviour, physical activity and diet) have a higher mean effect size
      than interventions with single (sedentary behaviour) component. Included studies
      (n = 25) were randomized controlled trials of children (<18 years) with
      intervention components aimed to reduce sedentary behaviour and measured BMI at
      pre- and post-intervention. Effect size was calculated as the mean difference in
      BMI change between children in an intervention group and a control group. Results
      indicated that sedentary behaviour interventions had a significant effect on BMI
      reduction. The pooled effect sizes of multi-component interventions (g = -0.060~
      0.089) did not differ from the single-component interventions (g = -0.154), and
      neither of them had a significant effect size on its own. Future paediatric
      obesity interventions may consider focusing on developing strategies to decrease
      multiple screen-related sedentary behaviours. 

PMID- 24588970
TI  - Inter-correlation of knowledge, attitude, and osteoporosis preventive behaviors
      in women around the age of peak bone mass.
AB  - BACKGROUND: As silent and preventable in nature, postmenopausal osteoporosis
      awareness should be raised among young women prior to an irreversible period of
      declining bone mass. We therefore decided to assess the inter-correlation of
      knowledge, attitude and osteoporosis preventive behaviors in women around the age
      of peak bone mass. METHODS: A cross-sectional study was conducted in 430 women
      aged 20-35 years. The participants' knowledge, attitude and behaviors concerning
      osteoporosis prevention were assessed along with demographic data using a four
      part questionnaire. The items in this questionnaire were established by extensive
      literature review, including the Guideline for Management of Osteoporosis of the
      Thai Osteoporosis Foundation (TOPF) 2010. The content was validated by experts in
      osteoporosis and reliability was obtained with a Cronbach's alpha score of 0.83.
      RESULTS: The mean age of women in this study was 29.4 +/- 4.6 years. Half of the
      participants (49.5%) had heard about osteoporosis, mostly from television (95.3%,
      n = 203/213) and the internet (72.8%, n = 155/213). Most women had certain
      knowledge (85.2%) and positive attitude towards osteoporosis (53.3%).
      Nevertheless, 80% of the studied population did not have appropriate osteoporosis
      behaviors. We found significant correlation between the level of attitudes and
      osteoporosis behaviors (adjusted odd ratio = 3.3 with 95% confidence interval of
      1.9-5.7); attitude and educational level (adjusted odd ratio = 2.2 with 95%
      confidence interval of 1.4-3.4); and attitude and knowledge (adjusted odd ratio =
      3.5 with 95% confidence interval of 1.8-6.8). CONCLUSION: Despite having certain
      knowledge about osteoporosis, the young women did not seem to have appropriate
      osteoporosis preventive behaviors. Developing a right attitude towards
      osteoporosis may be a key determinant to improving health practices in order to
      prevent osteoporosis.

PMID- 24588971
TI  - Membrane attack complex generation increases as a function of time in stored
      blood.
AB  - OBJECTIVE: To determine if the complement system, a potent mediator of
      inflammation, contributes to haemolysis during red blood cell (RBC) storage.
      BACKGROUND: RBCs in storage undergo structural and biochemical changes that may
      result in adverse patient outcomes post-transfusion. Complement activation on
      leukodepletion and during storage may contribute to the RBC storage lesion.
      METHODS/MATERIALS: We performed a cross-sectional analysis of aliquots of
      leukoreduced RBC units, stored for 1-6 weeks, for the levels of C3a, C5a, Bb,
      iC3b, C4d and C5b-9 [membrane attack complex (MAC)] by enzyme-linked
      immunosorbent assay (ELISA). RESULTS: We observed that only MAC levels
      significantly increased in RBC units as a function of storage time. We also
      observed that the level of C5b-9 bound to RBCs increased as a function of storage
      time. CONCLUSION: MAC levels increased over time, suggesting that MAC is the
      primary complement-mediated contributor to changes in stored RBCs. Inhibition of
      the terminal complement pathway may stabilise RBC functionality and extend shelf
      life.

PMID- 24588974
TI  - Bullous pemphigoid in a patient with multiple sclerosis being treated with human
      immunoglobulin.

PMID- 24588972
TI  - The transdermal formulation of rivastigmine improves caregiver burden and
      treatment adherence of patients with Alzheimer's disease under daily practice
      conditions.
AB  - BACKGROUND: Rivastigmine is the only cholinesterase inhibitor (ChEI) available as
      transdermal patch. The patch was developed to improve gastrointestinal
      tolerability and treatment adherence to higher dosages as compared with oral
      medication. Preferences of patients and caregivers for the patch were reported;
      however, neither patient compliance nor caregiver burden has yet been measured
      under routine practice conditions. METHODS: This was a prospective, multi-centre,
      observational study in patients with Alzheimer's disease treated with
      rivastigmine patch in Germany. To compare the transdermal with oral dosage forms,
      physicians were asked to enrol patients who recently switched from oral to
      transdermal medication. Beyond effectiveness and tolerability, outcome measures
      were drug adherence evaluated by the Morisky questionnaire, and caregiver burden,
      measured as the daily time expenditure for dressing the patient, controlling
      appearance and administration of medication. RESULTS: In total, 1104 outpatients
      (57.5% female gender; mean age 77 +/- 7 years) were enrolled in 220 sites. After
      6 months of treatment, 67.5% of patients had an improved Clinical Global
      Impression and the Mini-Mental State Examination score increased from 19.0 +/-
      5.1 to 20.0 +/- 5.2 (p < 0.001); 84.1% of patients were still on treatment, 64.6%
      on the target dose of 9.5 mg/day. Compliance and patient satisfaction with
      therapy continuously increased over the study period and average time savings of
      caregivers added up to 20 min/day. In general, tolerability was deemed good and
      there were no unexpected adverse events. CONCLUSIONS: Transdermal rivastigmine is
      an effective treatment alternative, which may improve adherence and treatment
      satisfaction of the patient and relieve the caregiver. Controlled parallel-group
      trials are warranted. CLINICAL TRIALS REGISTRATION: none (observational study).

PMID- 24588973
TI  - Root microbiome relates to plant host evolution in maize and other Poaceae.
AB  - Prokaryote-eukaryote interactions are primordial, but host selection of its
      bacterial community remains poorly understood. Because eukaryote evolution
      affects numerous traits shaping the ecology of their microbiome, we can expect
      that many evolutionary changes in the former will have the potential to impact on
      the composition of the latter. Consequently, the more phylogenetically distant
      the eukaryotic hosts, the more distinct their associated bacterial communities
      should be. We tested this with plants, by comparing the bacterial communities
      associated with maize genotypes or other Poaceae. 16S rRNA taxonomic microarray
      analysis showed that the genetic distance between rhizobacterial communities
      correlated significantly with the phylogenetic distance (derived from
      chloroplastic sequences) between Poaceae genotypes. This correlation was also
      significant when considering specific bacterial populations from all main
      bacterial divisions, instead of the whole rhizobacterial community. These results
      indicate that eukaryotic host's evolutionary history can be a significant factor
      shaping directly the assembly and composition of its associated bacterial
      compartment. 

PMID- 24588975
TI  - Adapting a scenario tree model for freedom from disease as surveillance
      progresses: the Canadian notifiable avian influenza model.
AB  - Scenario tree models with temporal discounting have been applied in four
      continents to support claims of freedom from animal disease. Recently, a second
      (new) model was developed for the same population and disease. This is a natural
      development because surveillance is a dynamic process that needs to adapt to
      changing circumstances - the difficulty is the justification for, documentation
      of, presentation of and the acceptance of the changes. Our objective was to
      propose a systematic approach to present changes to an existing scenario tree
      model for freedom from disease. We used the example of how we adapted the
      deterministic Canadian Notifiable Avian Influenza scenario tree model published
      in 2011 to a stochastic scenario tree model where the definition of sub
      populations and the estimation of probability of introduction of the pathogen
      were modified. We found that the standardized approach by Vanderstichel et al.
      (2013) with modifications provided a systematic approach to make and present
      changes to an existing scenario tree model. We believe that the new 2013 CanNAISS
      scenario tree model is a better model than the 2011 model because the 2013 model
      included more surveillance data. In particular, the new data on Notifiable Avian
      Influenza in Canada from the last 5 years were used to improve input parameters
      and model structure. 

PMID- 24588976
TI  - Prevalence and co-occurrence of hip dysplasia and elbow dysplasia in Dutch pure
      bred dogs.
AB  - Hip as well as elbow dysplasia (HD, ED) are developmental disorders leading to
      malformation of their respective joints. For a long time both disorders have been
      scored and targeted for improvement using selective breeding in several Dutch dog
      populations. In this paper all scores for both HD and ED, given to pure bred dogs
      in the Netherlands from 2002 to 2010, were analyzed. Heritabilities and
      correlations between HD and ED were calculated for the 4 most frequently scored
      breeds. Heritabilities ranged from 0.0 to 0.37 for HD related traits (FCI-score,
      osteoarthritis, congruity, shape and laxity (Norberg angle); FCI: Federation
      Cynologique Internationale) and from 0.0 to 0.39 for ED related traits (IEWG
      score, osteoarthritis, sclerosis and indentation; IEWG: International Elbow
      Working Group). HD related traits showed high genetic and residual correlations
      among each other but were only to a minor extent correlated with ED related
      traits, which also showed high correlations among each other. Genetic
      correlations were higher than residual correlations. Phenotypic and genetic
      trends since 2001 for the four most scored breeds were slightly positive but
      decreasing over time, indicating that selection over the past decade has not been
      effective. 

PMID- 24588977
TI  - The Norwegian Healthier Goats programme--a financial cost-benefit analysis.
AB  - The aim of this study was to evaluate the profitability to dairy goat farmers of
      participating in the Healthier Goats disease control and eradication programme
      (HG), which was initiated in 2001 and is still running. HG includes the control
      and eradication of caprine arthritis encephalitis (CAE), caseous lymphadenitis
      (CLA) and paratuberculosis (Johne's disease) in Norwegian goat herds. The
      profitability of participation was estimated in a financial cost-benefit analysis
      (CBA) using partial budgeting to quantify the economic consequences of infectious
      disease control through HG versus taking no action. Historical data were
      collected from 24 enrolled dairy goat herds and 21 herds not enrolled in HG, and
      supplemented with information from a questionnaire distributed to the same
      farmers. Expert opinions were collected to arrive at the best possible estimates.
      For some input parameters there were uncertainty due to imperfect knowledge, thus
      these parameters were modelled as PERT probability distributions and a stochastic
      simulation model was built. The CBA model was used to generate distributions of
      net present value (NPV) of farmers' net cash flows for choosing to enroll versus
      not enrolling. This was done for three selected milk quota levels of 30000L,
      50000L and 70000L, and both for before and after the introduction of a reduced
      milk price for the non-enrolled. The NPVs were calculated over time horizons of
      5, 10 and 20 years using an inflation-adjusted discount rate of 2.8% per annum.
      The results show that participation in HG on average was profitable over a time
      horizon of 10 years or longer for quota levels of 50000L and 70000L, although not
      without risk of having a negative NPV. If farmers had to pay all the costs
      themselves, participation in HG would have been profitable only for a time
      horizon beyond 20 years. In 2012, a reduced milk price was introduced for farmers
      not enrolled in HG, changing the decision criteria for farmers, and thus, the
      CBA. When the analysis was altered to account for these changes, the expected NPV
      was positive over five years for the 50000L quota, indicating an increased
      profitability of enrolling in HG. The sensitivity analysis showed that particular
      attention should be paid to work load and investment costs when planning for
      disease control programmes in the future. 

PMID- 24588978
TI  - A paramedic field supervisor's situational awareness in prehospital emergency
      care.
AB  - INTRODUCTION: Situational awareness (SA), or being aware of what is going on and
      what might happen next, is essential for the successful management of prehospital
      emergency care. However, far too little attention has been paid to the flow of
      information. Having the right information is important when formulating plans and
      actions. PROBLEM: The aim of this study was to analyze and describe the type of
      information that is meaningful for SA in the work of paramedic field supervisors,
      and to create an information profile for them in the context of prehospital
      emergency care. METHODS: Data were collected from January through March 2012 from
      semi-structured interviews with ten paramedic field supervisors representing four
      rescue departments in Finland. The interviews were based on three different types
      of real-life scenarios in the context of prehospital emergency care, and
      deductive content analysis was employed according to the information exchange
      meta-model. Data management and analysis were performed using Atlas.ti 7.
      RESULTS: A paramedic field supervisor information interest profile was
      formulated. The most important information categories were Events, Means, Action
      Patterns, and Decisions. The profile showed that paramedic field supervisors had
      four roles - situation follower, analyzer, planner and decision maker - and they
      acted in all four roles at the same time in the planning and execution phases.
      CONCLUSION: Paramedic field supervisors are multitasking persons, building SA by
      using the available data, combining it with extensive know-how from their working
      methods and competencies, and their tacit knowledge. The results can be used in
      developing work processes, training programs, and information systems.

PMID- 24588979
TI  - Chronic kidney disease and the ageing population.

PMID- 24588980
TI  - Do iron guidelines translate into good clinical practice for patients on
      haemodialysis?
AB  - BACKGROUND: Patients on haemodialysis (HD) have greater iron needs than the
      normal population. In 2004, the Caring for Australasians with Renal Impairment
      (CARI) group audited six Australian renal centres and found considerable
      variability in achievement of iron and haemoglobin targets. OBJECTIVES: The aim
      of this study was to determine whether intravenous iron guidelines and evidence
      translate into good clinical outcomes for patients on HD. DESIGN AND MEASUREMENT:
      Data were extracted from the Renal Anaemia Management database for the period of
      2007-2009. These data were compared with the target levels described in the CARI
      guidelines. RESULTS: Most patients were not achieving recommended haemoglobin,
      ferritin or transferrin saturation levels. Australian Aboriginal and Torres
      Strait Islander people were less likely to achieve targets. CONCLUSIONS: Iron
      guidelines are not translating into good clinical practice for patients on HD.
      This situation may be improved by updating the CARI guidelines (as has recently
      been carried out for haemoglobin targets), introduction of more consistent dosing
      protocols across hospitals and greater assessment of safe levels of cumulative
      iron and ferritin.

PMID- 24588981
TI  - Psychosocial distress in patients with end-stage kidney disease.
AB  - This is the first paper in a two-part Continuing Education (CE) series focusing
      on psychosocial care of patients with end-stage kidney disease (ESKD), which
      addresses a variety of psychological responses experienced by patients when
      adapting to the challenges posed by living with this long-term condition. The
      second paper will examine further the issues of coping and adjustment to ESKD and
      the need for renal supportive care to ensure person-centred holistic care is
      provided to patients. 

PMID- 24588986
TI  - Applying principles from behavioral economics to promote long-acting reversible
      contraceptive (LARC) methods.

PMID- 24588985
TI  - Fatal early peripheral post-reperfusion syndrome and the role of cutaneous signs.
AB  - The purpose of this report is to present the case of a 75-year-old male affected
      by right common femoral artery and abdominal aortic aneurysms. His clinical
      history was also characterised by post-ischaemic cardiomyopathy, arterial
      hypertension, chronic respiratory disease and peripheral arterial disease. We
      performed two surgical procedures: right femoral aneurysmectomy and femoro
      femoral bypass and subsequently a femoro-femoral crossover bypass plus right
      femoro-popliteal bypass below the knee. The second operation became necessary in
      order to treat acute occlusion of the right iliac-femoral arterial axis. The
      patient developed a progressive and aggressive lower limb post-perfusion syndrome
      associated to frank peripheral oedema, myocardial stunning, reperfusion
      arrhythmias, renal failure and respiratory distress. Cutaneous alterations
      (oedema of the leg, mottled skin and cyanosis of the foot) were more specific
      compared with Doppler ultrasound that showed the presence of adequate blood flow
      in the early phase. On the basis of this experience and of pertinent literature,
      this study represents a challenge for the understanding of the exact mechanism of
      origin and progression of post-reperfusion syndrome. 

PMID- 24588984
TI  - Aetiology, antimicrobial therapy and outcome of patients with community acquired
      severe sepsis: a prospective study in a Norwegian university hospital.
AB  - BACKGROUND: Severe sepsis is recognized as an inflammatory response causing organ
      dysfunction in patients with infection. Antimicrobial therapy is the mainstay of
      treatment. There is an ongoing demand for local surveillance of sepsis aetiology
      and monitoring of empirical treatment recommendations. The present study was
      established to describe the characteristics, quality of handling and outcome of
      patients with severe sepsis admitted to a Norwegian university hospital. METHODS:
      A one year prospective, observational study of adult community acquired case
      defined severe sepsis was undertaken. Demographics, focus of infection,
      microbiological findings, timing and adequacy of empirical antimicrobial agents
      were recorded. Clinical diagnostic practice was evaluated. Differences between
      categorical groups were analysed with Pearson's chi-squared test. Predictors of
      in-hospital mortality were identified in a multivariate stepwise backward
      logistic regression model. RESULTS: In total 220 patients were identified,
      yielding an estimated annual incidence of 0.5/1000 inhabitants. The focus of
      infection was established at admission in 69%. Respiratory tract infection was
      present in 52%, while genitourinary, soft tissue and abdominal infections each
      were found in 12-14%. Microbiological aetiology was identified in 61%; most
      prevalent were Streptococcus pneumoniae, Escherichia coli and Staphylococcus
      aureus. Independent predictors of in-hospital mortality were malignancy,
      cardiovascular disease, endocarditis, abdominal infections, undefined
      microbiological aetiology, delay in administration of empirical antimicrobial
      agents >= 6 hours and use of inadequate antimicrobial agents. In patients >= 75
      years, antimicrobial therapy was less in compliance with current recommendations
      and more delayed. CONCLUSIONS: Community acquired severe sepsis is common.
      Initial clinical aetiology is often revised. Compliance with recommendations for
      empirical antimicrobial treatment is lowest in elderly patients. Our results
      emphasizes that quick identification of correct source of infection, proper
      sampling for microbiological analyses, and fast administration of adequate
      antimicrobial agents are crucial points in the management of severe sepsis.

PMID- 24588987
TI  - The FiR 1 photon beam model adjustment according to in-air spectrum measurements
      with the Mg(Ar) ionization chamber.
AB  - The mixed neutron-photon beam of FiR 1 reactor is used for boron-neutron capture
      therapy (BNCT) in Finland. A beam model has been defined for patient treatment
      planning and dosimetric calculations. The neutron beam model has been validated
      with an activation foil measurements. The photon beam model has not been
      thoroughly validated against measurements, due to the fact that the beam photon
      dose rate is low, at most only 2% of the total weighted patient dose at FiR 1.
      However, improvement of the photon dose detection accuracy is worthwhile, since
      the beam photon dose is of concern in the beam dosimetry. In this study, we have
      performed ionization chamber measurements with multiple build-up caps of
      different thickness to adjust the calculated photon spectrum of a FiR 1 beam
      model. 

PMID- 24588988
TI  - A significant correlation between C - reactive protein levels in blood monocytes
      derived macrophages versus content in carotid atherosclerotic lesions.
AB  - BACKGROUND: Atherosclerosis is a complex disease involving different cell types,
      including macrophages that play a major role in the inflammatory events occurring
      in atherogenesis. C-Reactive Protein (CRP) is a sensitive systemic marker of
      inflammation and was identified as a biomarker of cardiovascular diseases.
      Histological studies demonstrate CRP presence in human atherosclerotic lesions,
      and we have previously shown that macrophages express CRP mRNA. CRP could be
      locally secreted in the atherosclerotic lesion by arterial macrophages and local
      regulation of CRP could affect its pro-atherogenic effects. Moreover, human blood
      derived macrophages (HMDM) expression of CRP could reflect atherosclerotic lesion
      secretion of CRP. METHODS: Ten type 2 diabetic patients and ten non-diabetic
      patients scheduled to undergo carotid endarterectomy were enrolled in this study,
      and their blood samples were used for serum CRP, lipid determination, and for
      preparation of HMDM further analyzed for their CRP mRNA expression and CRP
      content. Carotid lesions obtained from the patients were analyzed for their CRP
      and interleukin 6 (IL-6) content by immunohistochemistry. RESULTS: Lesions from
      diabetic patients showed substantially higher CRP levels by 62% (p = 0.05) than
      lesions from non diabetic patients, and CRP staining that co-localized with
      arterial macrophages. CRP carotid lesion levels positively correlated with CRP
      mRNA expression (r2 = 0.661) and with CRP content (r2 = 0.611) in the patient's
      HMDM. CONCLUSIONS: Diabetes up-regulated carotid plaques CRP levels and CRP
      measurements in HMDM could reflect atherosclerotic lesion macrophages secretion
      of CRP. Understanding the regulation of locally produced macrophage CRP in the
      arterial wall during atherogenesis could be of major importance in identifying
      the underlying mechanisms of inflammatory response pathways during atherogenesis.

PMID- 24588990
TI  - Potential gender and age differences in the performance of five condom-related
      behaviours in the United Kingdom.
AB  - Safer sex is important and comprises of a series of five condom-related
      behaviours: accessing, carrying, negotiating, using and disposing. This study
      explored potential gender and age differences in these condom-related behaviours.
      Data suggests gender differences exist for accessing, carrying and disposing
      behaviours. An age difference was seen in accessing behaviour. Therefore future
      safer sex interventions should acknowledge the potential gender and age
      differences in these condom-related behaviours. 

PMID- 24588989
TI  - Should women with chronic pelvic pain have adhesiolysis?
AB  - BACKGROUND: Pelvic adhesions are found in up to 50% of women with CPP during
      investigative surgeries and adhesiolysis is often performed as part of their
      management although the causal or casual association of adhesions, and the
      clinical benefit of adhesiolysis in the context of CPP is still unclear. Our aim
      was to test the hypothesis of whether laparoscopic adhesiolysis leads to
      significant pain relief and improvement in quality of life (QoL) in patients with
      chronic pelvic pain (CPP) and adhesions. METHODS: This was a double-blinded RCT.
      This study was conducted in 2 tertiary referral hospitals in United Kingdom over
      4 years. Women with chronic pelvic pain (CPP) were randomized into having
      laparoscopic adhesiolysis or diagnostic laparoscopy. Women were assessed at 0, 3
      and 6 months for Visual analogue scale scores (VAS) and Quality of Life (QoL)
      measures (SF-12 and EHP-30). RESULTS: A total of 92 participants were recruited;
      50 qualified to be randomized, with 26 in the adhesiolysis and 24 in the control
      group. The results are expressed in median (interquartile ranges). In women who
      underwent adhesiolysis, there was a significant improvement at 6 months in VAS
      scores (-17.5 (-36.0 - -5.0) compared to controls (-1.5 (-15.0 - 4.5; p = 0.048);
      SF-12 scores physical component score (25.0 (18.8 - 43.8)) compared to controls
      (6.3 (-6.3 - 18.8); p = 0.021), SF-12 emotional component score 32.5 (4.4 - 48.8)
      compared to controls -5 (-21.3 - 15.0); p < 0.0074) and EHP-30 emotional well
      being domain 32.5 (4.4 - 48.8) compared to the controls -5 (-21.3 - 15.0; p <
      0.0074). CONCLUSIONS: This study stopped before recruitment reached the
      statistically powered sample size due to difficulty with enrollment and lack of
      continued funding. In selected population of women presenting to the
      gynecological clinic with chronic pelvic pain, adhesiolysis in those who have
      adhesions may be of benefit in terms of improvement of pain and their quality of
      life. TRIAL REGISTRATION NUMBER: ISRCTN 43852269.

PMID- 24588991
TI  - An investigation of differing levels of experience and indices of task management
      in relation to scrub nurses' performance in the operating theatre: analysis of
      video-taped caesarean section surgeries.
AB  - BACKGROUND: Literature has identified failures in task management as direct
      determinants leading to accidents in the operating theatre. However, very few
      studies have investigated the factors underlying task management that directly
      influence the performance of the scrub nurses. The traditional belief that
      expertise is a general indicator of performance has been empirically investigated
      with varying results, but none has attempted to identify the task management
      determinants affecting performance, as influenced by the level of expertise.
      OBJECTIVES: (1) To examine any difference on task management behaviours between
      differing levels of experience during surgeries. (2) To correlate indices of task
      management with levels of performance evaluated by subject matter experts. DESIGN
      AND SETTING: 10 experienced and 10 novice scrub nurses were randomly selected
      from the Obstetrics and Gynaecology Department of a teaching hospital in
      Singapore. All nurses partook in a caesarean section surgery each, and their work
      processes were recorded via a scene camera donned by themselves. PARTICIPANTS: 20
      scrub nurses. METHODS: Two human factors experts independently mapped the task
      management processes onto a task management timeline, where individual tasks were
      coded, tallied and compared between levels of expertise. MAIN OUTCOME MEASURES:
      Reactive task management (task interruptions, task prioritizations), pro-active
      task management (anticipation, failures in anticipation), SPLINT scores
      (performance). RESULTS: Novice nurses showed lower resistance to interruptions
      during their tasks (58% more interruptions), especially to interruptions which
      were not triggered by the surgeon during their surgical counts (90% more
      interruptions). The novice nurses also displayed poorer/less ability to
      anticipate the surgeons' needs, taking longer time to handover instruments (39%
      longer) and making more mistakes (371% more errors). Subject matter experts rated
      the experienced nurses significantly higher in their cognitive non-technical
      skills performance than the novice nurses (32% higher). CONCLUSIONS: Experienced
      nurses performed better than novice nurses in all aspects of task management
      indices and expert evaluation. This suggested better task management as effected
      by expertise, displaying better prioritization, planning and awareness. With
      these findings, it would be easy and useful to draw causal effects that can in
      turn guide the design of training, leading to a desirable increase in levels of
      efficiency and patient safety in the operating theatre.

PMID- 24588992
TI  - The differential response of the Pben promoter of Pseudomonas putida mt-2 to BenR
      and XylS prevents metabolic conflicts in m-xylene biodegradation.
AB  - Pseudomonas putida mt-2 encompasses two alternative and potentially conflicting
      routes for benzoate metabolism, one meta pathway encoded by xyl genes of the pWW0
      plasmid and mastered by the Pm promoter and XylS, and one chromosomally encoded
      ortho pathway initiated by Pben and the BenR protein. Any cross-activation of
      Pben promoter by XylS ought to cause a metabolic conflict during the degradation
      of m-xylene because 3-methylbenzoate (3MBz) generated as an intermediate can be
      channelled through the ortho pathway and produce toxic dead-end metabolites. The
      activation of Pben by XylS was revisited using both reporter technology and
      tiling arrays targeted to the sequences of interest around messenger RNA
      initiation of both Pben and Pm promoters. Analysis of supersensitive luxCDABE
      fusions, inspection of xylX versus benA transcripts and growth tests of benR
      mutants indicated that the natural expression ranges of XylS under various
      conditions are insufficient to cause a significant cross-regulation of Pben
      whether cells face endogenous or exogenous 3MBz. This seems to stem from the
      nature of the operators for binding either transcriptional factor, which in the
      case of the Pben promoter of P. putida mt-2 appear to have evolved for avoiding a
      strong interaction with XylS. 

PMID- 24588993
TI  - Impact of removing mastoid process for advanced parotid cancer on facial nerve
      identification, preservation and reconstruction.
AB  - BACKGROUND: Advanced parotid cancers more than 4 cm are firmly fixed around the
      main trunk of the facial nerve that can be hardly detected in narrow working
      space between mastoid process and parotid cancer. Even though facial nerve was
      preserved, facial nerve stretching during surgery has significantly serious
      effect on postoperative facial palsy. OBJECTIVE: To evaluate usefulness of
      removing mastoid process in managing advanced parotid cancers to contribute
      identifying and preserving facial nerve. METHOD: The study was performed on 18
      advanced parotid cancers which was more than 4 cm and invaded around the facial
      nerve. Thirteen cases were fresh cases and 5 were recurrent cases.According to a
      modified Blair incision, the sternocleidomastoid muscle is detached from the
      mastoid process with electrocautery. When the mastoid process is removed, the
      main trunk of the facial nerve can be observed from stylomastoid foramen.This
      procedure was evaluated based on the duration of surgery, working space, and
      postoperative facial nerve function. RESULTS: In eleven cases, facial nerves were
      sacrificed. Negative margins were achieved in 100% of the patients. The mean
      duration for removing of the mastoid process to identify facial nerves was 4.6
      minutes. The mean size of the removed mastoid process was 2.1 cm in height and
      2.3 cm in width, and 1.8 cm in depth. The extended mean working space was 16.0
      cm3, and, as a result, the tumors could be resected without retraction.
      CONCLUSION: Removing the mastoid process for advanced parotid tumors facilitates
      identification of the facial nerve and better preservation of the facial nerve
      function.

PMID- 24588994
TI  - Soluble platelet-endothelial cell adhesion molecule-1, a biomarker of ventilator
      induced lung injury.
AB  - INTRODUCTION: Endothelial cell injury is an important component of acute lung
      injury. Platelet-endothelial cell adhesion molecule-1 (PECAM1) is a transmembrane
      protein that connects endothelial cells to one another and can be detected as a
      soluble, truncated protein (sPECAM1) in serum. We hypothesized that injurious
      mechanical ventilation (MV) leads to shedding of PECAM1 from lung endothelial
      cells resulting in increasing sPECAM1 levels in the systemic circulation.
      METHODS: We studied 36 Sprague-Dawley rats in two prospective, randomized,
      controlled studies (healthy and septic) using established animal models of
      ventilator-induced lung injury. Animals (n = 6 in each group) were randomized to
      spontaneous breathing or two MV strategies: low tidal volume (VT) (6 ml/kg) and
      high-VT (20 ml/kg) on 2 cmH2O of positive end-expiratory pressure (PEEP). In low
      VT septic animals, 10 cmH2O of PEEP was applied. We performed pulmonary
      histological and physiological evaluation and measured lung PECAM1 protein
      content and serum sPECAM1 levels after four hours ventilation period. RESULTS:
      High-VT MV caused severe lung injury in healthy and septic animals, and decreased
      lung PECAM1 protein content (P < 0.001). Animals on high-VT had a four- to six
      fold increase of mean sPECAM1 serum levels than the unventilated counterpart
      (35.4 +/- 10.4 versus 5.6 +/- 1.7 ng/ml in healthy rats; 156.8 +/- 47.6 versus
      35.6 +/- 12.6 ng/ml in septic rats) (P < 0.0001). Low-VT MV prevented these
      changes. Levels of sPECAM1 in healthy animals on high-VT MV paralleled the
      sPECAM1 levels of non-ventilated septic animals. CONCLUSIONS: Our findings
      suggest that circulating sPECAM1 may represent a promising biomarker for the
      detection and monitoring of ventilator-induced lung injury.

PMID- 24588996
TI  - Guidance on anti-D administration in early pregnancy.

PMID- 24588997
TI  - Authors' reply: guidance on anti-D administration in early pregnancy.

PMID- 24588998
TI  - Authors' reply: cervical surgery for cervical intraepithelial neoplasia and
      prolonged time to conception of a live birth.

PMID- 24588999
TI  - Cervical surgery for cervical intraepithelial neoplasia and prolonged time to
      conception of a live birth.

PMID- 24589000
TI  - Changes in risk factors for preterm birth in Western Australia 1984-2006.

PMID- 24589001
TI  - Authors' reply: changes in risk factors for preterm birth in Western Australia
      1984-2006.

PMID- 24589002
TI  - #BlueJC: BJOG and Katherine Twining Network collaborate to facilitate post
      publication peer review and enhance research literacy via a Twitter journal club.

PMID- 24589003
TI  - Authors' reply: #BlueJC: BJOG and Katherine Twining Network collaborate to
      facilitate post-publication peer review and enhance research literacy via a
      Twitter journal club.

PMID- 24589004
TI  - A report from #BlueJC: when is the best time to schedule an elective caesarean?

PMID- 24589005
TI  - Elective caesarean section at 38 versus 39 weeks of gestation: neonatal and
      maternal outcomes in a randomised controlled trial Are we trivialising neonatal
      intensive care unit admissions?

PMID- 24589006
TI  - Authors' reply: elective caesarean section at 38 versus 39 weeks of gestation:
      neonatal and maternal outcomes in a randomised controlled trial Are we
      trivialising neonatal intensive care unit admissions?

PMID- 24589007
TI  - Author's reply: elective caesarean section at 38 versus 39 weeks of gestation:
      neonatal and maternal outcomes in a randomised controlled trial.

PMID- 24589008
TI  - Elective caesarean section at 38 versus 39 weeks of gestation: neonatal and
      maternal outcomes in a randomised controlled trial.

PMID- 24589009
TI  - BJOG editor's choice: global obstetrics.

PMID- 24589010
TI  - The impact of brief tobacco treatment training on practice behaviours, self
      efficacy and attitudes among healthcare providers.
AB  - INTRODUCTION AND PURPOSE: The need for aggressive efforts to help tobacco users
      quit remains a healthcare priority. Brief interventions delivered in the
      healthcare environment continue to be a valuable component of a comprehensive
      tobacco control policy. Unfortunately, such treatments are offered less often
      than desired, and quality is variable. Previous research has demonstrated the
      value of training experiences in increasing treatment availability, quality, as
      well as improving clinical outcomes. Less is known about how specific clinical
      activities and other features are impacted as a function of training. These
      issues were explored within the context of a standardised 5A's (ASK, ADVISE,
      ASSESS, ASSIST, ARRANGE) brief intervention training program. METHODS: A variety
      of healthcare providers participated in this study. Survey methodology was
      employed to collect Practice Behaviour, Self-Efficacy and Attitude ratings at
      pretraining, post training and 6-month follow-up. Linear mixed effects models
      were used to evaluate primary outcomes, and linear regression to explore the
      relationships among clinical variables. RESULTS: Pretraining data suggested
      overall modest levels of tobacco treatment activity, with limited direct
      intervention (ASSIST) or follow-up (ARRANGE) efforts. The training experience was
      shown to have a substantial and sustained impact on 5A's Practice Behaviour
      ratings, and other clinical indicators (all Pre vs. Post and Pre vs. Follow-up
      comparisons p < 0.001). Self-Efficacy at post training predicted practice
      behaviours at follow-up (for ADVISE, ASSESS, ASSIST and ARRANGE: all p's < 0.05).
      CONCLUSIONS: The value of a structured training experience was confirmed, and
      findings served to clarify the specific nature of training program impact.

PMID- 24589011
TI  - Effect of feeding level on ileal and total tract digestibility of nutrients and
      energy from soybean meal-based diets for piglets.
AB  - A total of 36 piglets with an initial body weight (BW) of 5.6 +/- 0.7 kg, fitted
      with simple T-cannulas at the distal ileum, were used to evaluate the effect of
      three graded feeding levels (50, 75 or 100 g/kg BW(0.75) day) on apparent ileal
      digestibility (AID) and total tract digestibility (ATTD) of dry matter (DM),
      nitrogen (N) and energy, and on ATTD of organic matter (OM), ether extracts (EE),
      neutral detergent fibre (NDF), acid detergent fibre (ADF) and digestible (DE),
      metabolisable (ME) and net energy (NE) content in soybean meal (SBM)-casein
      cornstarch-based diets. The AID of DM, N and energy and ATTD of NDF, ADF and EE
      in the diets were not affected (p > 0.05) by the feed intake (FI) level. There
      was a small decrease in ATTD of DM, N (CP), OM, ash and energy, and in DE, ME and
      NE content in the diets (p < 0.05) with increasing FI level. The net
      disappearance in the large intestine (in % of ileal recovery) decreased for DM, N
      and energy (p < 0.05) with increasing FI level. The design of the study allowed
      for estimating ileal endogenous loss of N and total tract endogenous loss of ash,
      N and EE, for estimating corresponding true ileal and total tract digestibility
      values, and for estimating urinary endogenous N loss. High variability in
      estimates of ileal endogenous N loss and total tract endogenous losses of N, EE
      and ash reflects great variation in individual endogenous losses between animals.
      Estimation of true total tract digestibility of N, EE and ash by regression
      analysis was affected by their decrease in ATTD with increasing FI level, as
      estimates for true digestibility were lower compared to their apparent values.
      The present results suggest that FI level can affect both apparent and true total
      tract nutrient digestibility in piglets.

PMID- 24589012
TI  - Exercise as an add-on strategy for the treatment of major depressive disorder: a
      systematic review.
AB  - Antidepressants are currently the treatment of choice for major depressive
      disorder (MDD). Nevertheless, a high percentage of patients do not respond to a
      first-line antidepressant drug, and combination treatments and augmentation
      strategies increase the risk of side effects. Moreover, a significant proportion
      of patients are treatment-resistant. In the last 30 years, a number of studies
      have sought to establish whether exercise could be regarded as an alternative to
      antidepressants, but so far no specific analysis has examined the efficacy of
      exercise as an adjunctive treatment in combination with antidepressants. We
      carried out a systematic review to evaluate the effectiveness of exercise as an
      adjunctive treatment with antidepressants on depression. A search of relevant
      papers was carried out in PubMed/Medline, Google Scholar, and Scopus with the
      following keywords: "exercise," "physical activity," "physical fitness,"
      "depressive disorder," "depression," "depressive symptoms," "add-on,"
      "augmentation," "adjunction," and "combined therapy." Twenty-two full-text
      articles were retrieved by the search. Among the 13 papers that fulfilled our
      inclusion criteria, we found methodological weaknesses in the majority. However,
      the included studies showed a strong effectiveness of exercise combined with
      antidepressants. Further analyses and higher quality studies are needed;
      nevertheless, as we have focused on a particular intervention (exercise in
      adjunction to antidepressants) that better reflects clinical practice, we can
      hypothesize that this strategy could be appropriately and safely translated into
      real-world practice. 

PMID- 24589013
TI  - Inter- and intra-lower limb joint coordination of non-expert classical ballet
      dancers during tiptoe standing.
AB  - The main objective of this study was to compare ballet dancers' and non-dancers'
      joint coordination during tiptoe standing. Nine female non-expert ballet dancers
      and nine female non-dancers were asked to perform heel-toe and tiptoe standing
      for approximately 30s, during which the center of pressure (COP) and kinematic
      data from the metatarsophalangeal, ankle, knee, and hip joints were measured.
      Principal component analysis was performed on the angular displacements to
      determine joint coordination. The weighting vectors suggested that dancers' ankle
      and knee joints fluctuated in-phase in the anteroposterior direction, whereas all
      combinations of adjacent joints had anti-phase coordination for non-dancers. In
      addition, there was a significant difference in the intra-joint coordination
      pattern between groups. In particular, dancers' metatarsophalangeal (MP) and
      ankle joints tended to sway to the left-front or right-rear. However, there were
      no differences between the groups in the path length or rectangular COP. These
      results suggest that dancers maintained quiet postures via a decrease in the
      mechanical degree of freedom and that postural expertise may not be determined
      from a traditional COP analysis, even during unstable tiptoe standing. This in
      phase coordination, which has an arch-like configuration, could be characteristic
      of dancers' lithe legs. 

PMID- 24589014
TI  - Changes in peripheral blood B cell subsets at diagnosis and after treatment with
      disease-modifying anti-rheumatic drugs in patients with rheumatoid arthritis:
      correlation with clinical and laboratory parameters.
AB  - OBJECTIVE: To assess variation in peripheral blood B lymphocyte subsets in
      rheumatoid arthritis (RA). METHODS: B lymphocyte subsets in disease-modifying
      anti-rheumatic drug (DMARD)-naive patients with RA (n = 30), patients with RA
      treated with DMARDs (n = 73) and healthy controls (n = 46) were analyzed by flow
      cytometry. Total B cells, total memory B cells, immunoglobulin M (IgM) memory B
      cells, switched memory B cells, non-switched memory B cells, CD21lo B cells,
      transitional B cells and plasmablasts were measured. Correlation with clinical
      and laboratory parameters was performed. RESULTS: Total memory B cells, IgM
      memory B cells and non-switched memory B cells were reduced in RA patients at
      diagnosis compared to controls (P < 0.05). In patients with treated RA, there was
      a further reduction of total B cells, CD21lo cells, transitional B cells and
      plasmablasts, compared to controls (P < 0.05). The reduction in absolute numbers
      of total B cells, switched memory B cells, CD21lo cells, transitional B cells and
      plasmablasts in treated RA patients was significant (P < 0.05) even when compared
      to the DMARD-naive patients. Only treatment responders (Disease Activity Score <
      3.2) had reduced total B cells and absolute numbers of switched and IgM memory B
      cells (P < 0.05). In patients requiring leflunomide, total memory B cells, IgM
      memory B cells, non-switched memory B cells and absolute numbers of switched
      memory B cells were reduced compared with the remainder of the patient group (P <
      0.05). CONCLUSION: There is reduction of various B cell subsets in RA patients at
      diagnosis. Treatment with DMARDs leads to further reduction in additional B cell
      subsets without correction of the abnormalities. Reduction in individual subsets
      may predict RA patients requiring more intensive therapy.

PMID- 24589016
TI  - Evaluation of the impact of tromethamine edetate disodium dihydrate on
      antimicrobial susceptibility of Pseudomonas aeruginosa in biofilm in vitro.
AB  - BACKGROUND: Biofilm formation by Pseudomonas aeruginosa has been documented in
      canine otic isolates. An increase in minimal inhibitory concentration (MIC) for
      specific antibiotics has been noted for biofilm-embedded bacteria. Tromethamine
      edetate disodium dihydrate buffered to pH 8 with tromethamine hydrochloride and
      deionized water (Triz-EDTA((r))) has been documented to potentiate bactericidal
      activity when used in combination with topical antibiotics, but the impact on
      biofilm-embedded bacteria is unknown. HYPOTHESIS/OBJECTIVES: The objective of
      this study was to evaluate the impact of Triz-EDTA((r)) use on in vitro
      antimicrobial susceptibility of biofilm-embedded P. aeruginosa. METHODS: Biofilm
      formation was documented using a microtitre plate assay. Broth microdilution was
      used to assess the MIC of neomycin, polymyxin B, enrofloxacin and gentamicin for
      the biofilm-embedded bacteria. The microtitre plate assay was again used to
      assess the MIC of neomycin, polymyxin B, enrofloxacin and gentamicin for biofilm
      embedded bacteria with added Triz-EDTA((r)). RESULTS: Thirty-one isolates from
      dogs with otitis were tested. Addition of Triz-EDTA((r)) significantly reduced
      MICs for neomycin (P < 0.003) and gentamicin (P < 0.02) but not for polymyxin B
      (P = 0.3). Enrofloxacin MICs increased in the presence of Triz-EDTA (P < 0.036).
      CONCLUSIONS AND CLINICAL IMPORTANCE: Triz-EDTA((r)) may be a useful adjunctive
      treatment for chronic cases of Pseudomonas otitis where biofilms may have
      developed, if gentamicin or neomycin is to be used as a topical treatment. In
      vivo study is required to confirm this effect.

PMID- 24589015
TI  - Comparative impact of antiretroviral drugs on markers of inflammation and immune
      activation during the first two years of effective therapy for HIV-1 infection:
      an observational study.
AB  - BACKGROUND: Few studies have compared the impact of different antiretroviral
      regimens on residual immune activation and inflammation with discordant results.
      Aim of the study was to investigate the impact of various antiretroviral regimens
      on markers of immune activation and inflammation during the first two years of
      effective therapy. METHODS: We studied HIV-infected antiretroviral-naive patients
      who began cART with either abacavir/lamivudine or tenofovir/emtricitabine,
      combined with ritonavir-boosted lopinavir (LPV/r), atazanavir (ATV/r) or
      efavirenz (EFV). All the patients had a virological response within 6 months,
      which was maintained for 2 years with no change in their ART regimen. C-reactive
      protein (hs-CRP), interleukin-6 (IL-6), soluble CD14 (sCD14), monokine induced by
      interferon-gamma (MIG) and interferon-gamma-inducible protein-10 (IP-10) were
      measured in stored plasma obtained at cART initiation and 24 months later. Mean
      changes from baseline were analyzed on loge-transformed values and multivariable
      linear regression models were used to study the effect of the treatment
      components, after adjusting for factors that might have influenced the choice of
      ART regimen or biomarker levels. Differences were expressed as the mean fold
      change percentage difference (Delta). RESULTS: Seventy-eight patients (91% males)
      with a median age of 43 years met the inclusion criteria. Their median baseline
      CD4 cell count was 315/mm3 and HIV-1 RNA level 4.6 log10 copies/ml. During the 2
      years study period, IL-6, IP-10 and MIG levels fell significantly, while hs-CRP
      and sCD14 levels remained stable. IP-10 and MIG levels declined significantly
      less strongly with ATV/r than with EFV (IP-10Delta -57%, p = 0.011; MIGDelta 
      136%, p = 0.007), while no difference was noted between LPV/r and EFV. The
      decline in IL-6 did not differ significantly across the different treatment
      components. CONCLUSIONS: After the first 2 years of successful cART, IL-6, IP-10
      and MIG fell markedly while hs-CRP and sCD14 levels remained stable. The only
      impact of ART regimen was a smaller fall in markers of immune activation with
      ATV/r than with EFV. Our results suggest that these markers could be worthwhile
      when evaluating new antiretroviral drugs.

PMID- 24589017
TI  - The genome of Syntrophorhabdus aromaticivorans strain UI provides new insights
      for syntrophic aromatic compound metabolism and electron flow.
AB  - How aromatic compounds are degraded in various anaerobic ecosystems (e.g.
      groundwater, sediments, soils and wastewater) is currently poorly understood.
      Under methanogenic conditions (i.e. groundwater and wastewater treatment),
      syntrophic metabolizers are known to play an important role. This study explored
      the draft genome of Syntrophorhabdus aromaticivorans strain UI and identified the
      first syntrophic phenol-degrading phenylphosphate synthase (PpsAB) and
      phenylphosphate carboxylase (PpcABCD) and syntrophic terephthalate-degrading
      decarboxylase complexes. The strain UI genome also encodes benzoate degradation
      through hydration of the dienoyl-coenzyme A intermediate as observed in Geobacter
      metallireducens and Syntrophus aciditrophicus. Strain UI possesses electron
      transfer flavoproteins, hydrogenases and formate dehydrogenases essential for
      syntrophic metabolism. However, the biochemical mechanisms for electron transport
      between these H2 /formate-generating proteins and syntrophic substrate
      degradation remain unknown for many syntrophic metabolizers, including strain UI.
      Analysis of the strain UI genome revealed that heterodisulfide reductases
      (HdrABC), which are poorly understood electron transfer genes, may contribute to
      syntrophic H2 and formate generation. The genome analysis further identified a
      putative ion-translocating ferredoxin : NADH oxidoreductase (IfoAB) that may
      interact with HdrABC and dissimilatory sulfite reductase gamma subunit (DsrC) to
      perform novel electron transfer mechanisms associated with syntrophic metabolism.

PMID- 24589019
TI  - Estimating the number of injection drug users in greater Victoria, Canada using
      capture-recapture methods.
AB  - BACKGROUND: Population size estimation is critical for planning public health
      programmes for injection drug users. Estimation is difficult, as these
      populations are considered 'hidden' or 'hard to reach'. The currently accepted
      population size estimate for greater Victoria, Canada is between 1,500 and 2,000
      individuals, which is dated prior to the year 2000, and is likely an
      underestimate. METHODS: We used three mark-recapture methods (the Lincoln
      Petersen estimator, Huggins' model, and Pledger's model) to estimate population
      size using cross-sectional survey data collected in 2003 and 2005. Data come from
      a closed population with two time-ordered samples from the same source. We
      compare our estimates with the currently accepted estimate that is based on the
      registry of a Victoria needle exchange. RESULTS: All methods provided population
      size estimates that were higher than the currently accepted estimate. Huggins'
      method produced wider confidence intervals. Point estimates of population size
      from the three methods ranged from 3,329 to 3,342. CONCLUSIONS: Our estimates
      will aid health authorities in planning for harm reduction programmes. Repeating
      the methods as further phases of I-Track data become available will ensure that
      the population estimates remain up to date.

PMID- 24589020
TI  - The antibacterial activity, antioxidant activity and selectivity index of leaf
      extracts of thirteen South African tree species used in ethnoveterinary medicine
      to treat helminth infections.
AB  - BACKGROUND: Diseases caused by bacteria remain a major challenge globally and
      particularly in sub-Saharan Africa. The plants used in this study have been used
      in South Africa to treat helminth infections in livestock and humans. In a
      previous study we found a correlation between antifungal and anthelmintic
      activity in some cases. In this study we examined other potential uses of these
      thirteen plant species by determining the antibacterial and antioxidant activity
      of the leaf acetone extracts.The antibacterial activity was determined by using a
      serial microdilution method against Staphylococcus aureus, Pseudomonas
      aeruginosa, Escherichia coli and Enterococcus faecalis. Bioautography was used to
      determine the number of antibacterial compounds. The antioxidant activity was
      determined using the ABTS and DPPH methods. RESULTS: Maesa lanceolata and
      Leucosidea sericea with an MIC of 0.02 mg/ml had excellent antibacterial activity
      against Enterococcus faecalis and Pseudomonas aeruginosa. There was a poor
      correlation between antioxidant activity and antibacterial activity with R2 =
      0.143. This is because antibacterial activity is mainly related to non-polar
      compounds and antioxidant activity to polar compounds. Maesa lanceolata extracts
      had a low cytotoxicity with a selectivity index of 5.2, 2.6, 2.6 and 1.3 for P.
      aeruginosa, E. faecalis, E. coli and S. aureus respectively. Strychnos mitis
      extracts had a therapeutic index of 1.1 for E. coli. CONCLUSIONS: This study
      shows that plant extracts of some species used in ethnoveterinary medicine as
      anthelmintic may also have excellent antibacterial activity.

PMID- 24589018
TI  - Dose-dependent inhibition of gastric injury by hydrogen in alkaline electrolyzed
      drinking water.
AB  - BACKGROUND: Hydrogen has been reported to relieve damage in many disease models,
      and is a potential additive in drinking water to provide protective effects for
      patients as several clinical studies revealed. However, the absence of a dose
      response relationship in the application of hydrogen is puzzling. We attempted to
      identify the dose-response relationship of hydrogen in alkaline electrolyzed
      drinking water through the aspirin induced gastric injury model. METHODS: In this
      study, hydrogen-rich alkaline water was obtained by adding H2 to electrolyzed
      water at one atmosphere pressure. After 2 weeks of drinking, we detected the
      gastric mucosal damage together with MPO, MDA and 8-OHdG in rat aspirin induced
      gastric injury model. RESULTS: Hydrogen-dose dependent inhibition was observed in
      stomach mucosal. Under pH 8.5, 0.07, 0.22 and 0.84 ppm hydrogen exhibited a high
      correlation with inhibitory effects showed by erosion area, MPO activity and MDA
      content in the stomach. Gastric histology also demonstrated the inhibition of
      damage by hydrogen-rich alkaline water. However, 8-OHdG level in serum did not
      have significant hydrogen-dose dependent effect. pH 9.5 showed higher but not
      significant inhibitory response compared with pH 8.5. CONCLUSIONS: Hydrogen is
      effective in relieving the gastric injury induced by aspirin-HCl, and the
      inhibitory effect is dose-dependent. The reason behind this may be that hydrogen
      rich water directly interacted with the target tissue, while the hydrogen
      concentration in blood was buffered by liver glycogen, evoking a suppressed dose
      response effect. Drinking hydrogen-rich water may protect healthy individuals
      from gastric damage caused by oxidative stress.

PMID- 24589021
TI  - Post-mortem timing of skeletal muscle biochemical and mechanical degradation.
AB  - Fresh cadaveric human tissue is a valuable resource that is used to address
      important clinical questions. However, it is unknown how post-mortem time impacts
      skeletal muscle mechanical and biochemical properties. We simulated morgue
      conditions in rabbits and tested the passive mechanical properties of muscle
      bundles, and the degradation of myosin heavy chain, collagen, and titin at
      specific intervals up to 7 days post-mortem. While a great deal of inter-specimen
      variability was observed, it was independent of post-mortem time. Passive
      mechanics, myosin heavy chain, and collagen content were all unaffected while the
      titin protein degraded up to 80% over 7 days post-mortem. These data indicate
      that fresh cadaveric tissue may be used for passive mechanical testing and that
      certain biochemical properties are unchanged up to 7 days after death. 

PMID- 24589022
TI  - Energy exchange between subject and belt during treadmill walking.
AB  - Treadmill walking aims to simulate overground walking, but intra-stride belt
      speed variations of treadmills result in some interaction between treadmill and
      subject, possibly obstructing this aim. Especially in self-paced treadmill
      walking, in which the belt speed constantly adjusts to the subject, these
      interactions might affect the gait pattern significantly. The aim of this study
      was to quantify the energy exchange between subject and treadmill, during the
      fixed speed (FS) and self-paced (SP) modes of treadmill walking. Eighteen
      subjects walked on a dual-belt instrumented treadmill at both modes. The energy
      exchange was calculated as the integration of the product of the belt speed
      deviation and the fore-aft ground reaction force over the stride cycle. The total
      positive energy exchange was 0.44 J/stride and the negative exchange was 0.11
      J/stride, which was both less than 1.6% of the performed work on the center of
      mass. Energy was mainly exchanged from subject to treadmill during both the
      braking and propulsive phase of gait. The two treadmill modes showed a similar
      pattern of energy exchange, with a slightly increased energy exchange during the
      braking phase of SP walking. It is concluded that treadmill walking is only
      mildly disturbed by subject-belt interactions when using instrumented treadmills
      with adequate belt control.

PMID- 24589023
TI  - Ogilvie syndrome: a potentially life-threatening phenotype of immobilization
      hypercalcemia.
AB  - Ogilvie syndrome, also known as acute colonic pseudo-obstruction, is
      characterized by the clinical presentation and imaging evidence of acute colonic
      obstruction in the absence of a mechanical cause. Several comorbidities and
      serious associated medical or surgical conditions have been described to be
      relevant to this syndrome. In general, a preferred initial management with
      favorable treatment outcomes is virtually to correct underlying disorders.
      Although disrupted electrolyte homeostasis may induce impaired colonic motility,
      hypercalcemia secondary to immobilization as a major culprit in this syndrome has
      rarely been studied. In this report, we profiled radiographic features,
      therapeutic strategies, and pathogenetic hypothesis of this clinical entity and
      highlighted the need for clinicians to maintain awareness of this distinct
      manifestation.

PMID- 24589024
TI  - Cholinergic symptoms with low serum cholinesterase from therapeutic
      cholinesterase inhibitor toxicity.
AB  - Although cholinesterase inhibitors have been frequently used in the treatment of
      Alzheimer disease, its effects on serum cholinesterase concentrations have been
      rarely described. We described significant depression of serum cholinesterase
      levels due to cholinesterase inhibitor toxicity from redundant use of donepezil
      and rivastigmine in a 78-year-old man. Recovery of serum cholinesterase level was
      noted upon drug discontinuation and cholinergic symptom resolution. Serum
      cholinesterase level can be used as a biomarker for central cholinesterase
      inhibitor toxicity.

PMID- 24589025
TI  - Tryptophan immunoadsorption for the treatment of autoimmune encephalitis.
AB  - BACKGROUND AND PURPOSE: Detection of autoantibodies against neuronal surface
      antigens and their correlation with the pattern and severity of symptoms led to
      the definition of new autoimmune-mediated forms of encephalitis and was essential
      for the initiation of immunotherapies including plasma exchange. The elimination
      of autoantibodies using selective immunoadsorption (IA) is a pathophysiologically
      guided therapeutic approach but has not yet been evaluated in a separate
      analysis. METHODS: A retrospective analysis was performed of patients with
      autoimmune encephalitis who were treated with tryptophan IA in six neurological
      clinics between 2009 and 2013. The modified Rankin scale (mRS) was used to
      evaluate neurological status before and after IA. RESULTS: Data on 13 patients
      were documented. Twelve patients were positive for specific autoantibodies (NMDA
      R, GABA, GAD, Lgl1). Patients received a series of a median of six IA treatments.
      Median mRS of all patients was 3.0 before IA and 2.0 after IA (P < 0.001). Eleven
      patients improved by at least one point in mRS after IA. CONCLUSION: For
      autoimmune-mediated forms of encephalitis rapid elimination of autoantibodies
      with selective IA seems to be an effective therapeutic option as part of
      multimodal immune therapy.

PMID- 24589026
TI  - Single port laparoscopic surgery for patients with complex and recurrent Crohn's
      disease.
AB  - BACKGROUND: Single port laparoscopic surgery (SPLS) is a modified access
      technique allowing grouping of instruments at a single parietal site. It is
      intuitively appealing specifically for patients with Crohn's disease (CD) as its
      minimal invasiveness favors cosmesis and facilitates any future (re)operation.
      METHODS: Consecutive patients presenting either electively or urgently for
      resectional surgery for CD over a 36 month period were considered for SPLS using,
      by preference, a transumbilical 'Surgical Glove Port'. Standard, straight
      laparoscopic instrumentation was used without additional resources. RESULTS: Of
      33 consecutive, unselected patients, 28 (92%) had their procedure initiated by
      SPLS including those needing urgent intervention (n=15) and those with prior
      abdominal operation (n=8), obstruction (n=7), mass (n=6), fistula (n=6) and/or
      abscess (n=4). The median (range) age and BMI of the patients were 31 (17-69)
      years and 21.3 (18.6-28) kg/m2 respectively. 31 had ileocolonic resection (6 with
      recurrent disease) while two underwent segmental colectomy. No-one suffered
      intraoperative or anastomotic complication. Both conversion (15%) and
      postoperative complication (13 Clavian-Dindo complications - I: 8; II: 2; IIIa:
      3) rates were predominantly reflective of patient and disease complexity. Median
      (range) postoperative day of discharge was 6 (3-33) overall and 5 (3-18) in those
      completed by SPLS. There was one early readmission (for infectiouscolitis) and
      median follow-up is now 21 months. CONCLUSIONS: Complex and recurrent Crohn's
      resections can be performed by SPLS in the majority of patients presenting
      elective or urgently for surgery. The Surgical Glove Port performs capably and,
      by minimizing cost, can facilitate broad embrace of this approach.

PMID- 24589029
TI  - Abstracts of the SpROGs 2013 Conference, 5-6 December 2013, Nottingham, United
      Kingdom.

PMID- 24589027
TI  - Endemic fungal infections in solid organ and hematopoietic cell transplant
      recipients enrolled in the Transplant-Associated Infection Surveillance Network
      (TRANSNET).
AB  - BACKGROUND: Invasive fungal infections are a major cause of morbidity and
      mortality among solid organ transplant (SOT) and hematopoietic cell transplant
      (HCT) recipients, but few data have been reported on the epidemiology of endemic
      fungal infections in these populations. METHODS: Fifteen institutions belonging
      to the Transplant-Associated Infection Surveillance Network prospectively
      enrolled SOT and HCT recipients with histoplasmosis, blastomycosis, or
      coccidioidomycosis occurring between March 2001 and March 2006. RESULTS: A total
      of 70 patients (64 SOT recipients and 6 HCT recipients) had infection with an
      endemic mycosis, including 52 with histoplasmosis, 9 with blastomycosis, and 9
      with coccidioidomycosis. The 12-month cumulative incidence rate among SOT
      recipients for histoplasmosis was 0.102%. Occurrence of infection was bimodal; 28
      (40%) infections occurred in the first 6 months post transplantation, and 24
      (34%) occurred between 2 and 11 years post transplantation. Three patients were
      documented to have acquired infection from the donor organ. Seven SOT recipients
      with histoplasmosis and 3 with coccidioidomycosis died (16%); no HCT recipient
      died. CONCLUSIONS: This 5-year multicenter prospective surveillance study found
      that endemic mycoses occur uncommonly in SOT and HCT recipients, and that the
      period at risk extends for years after transplantation.

PMID- 24589028
TI  - Effect of physical training on nutrient digestibility and faecal fermentative
      parameters in Standardbred horses.
AB  - This study aimed at evaluating, in previously inactive Standardbreds horses, the
      effect of 5 weeks of an exercise training programme on nutrient digestibility and
      faecal fermentative parameters (FFPs). As an increase in digestibility had
      previously been reported in trained endurance horses, we hypothesized that
      similar results would be found in horses being trained for other types of
      exercise on a different type of diet. After 3 weeks of dietary adaptation, a
      digestibility trial (DT1) was undertaken, over 3 days, in eight untrained
      Standardbreds with a fresh faecal sample being collected on the second day for
      FFP determinations. Six of the eight horses undertook a training programme, and
      after 5 weeks of exercise, the DT and the FFP measurements were then repeated
      (DT2). DT2 began after 3 days of inactivity. The same natural meadow hay (H) and
      pelleted complementary feed (CF) were fed throughout. For 5 days before the DTs,
      horses were fed 2.1% BW on a dry matter basis (55:45 ratio H:CF). Body weight and
      body condition score remained constant. Apparent digestibility of dry matter,
      organic matter, neutral detergent fibre, hemicellulose, crude protein and gross
      energy, as well as faecal total volatile fatty acids (VFA), acetate and
      propionate concentrations were significantly (p < 0.05) higher at DT2 than at
      DT1. A 5-week exercise programme had a positive impact on nutrient digestibility
      and FFP. Training may improve dietary energy supply, in particular via increased
      hindgut VFA production. The potential improvement of digestive efficiency with
      training should be taken into account when formulating nutritional
      recommendations for the exercising horse, particularly when performing light
      work, which is low-intensity exercise for 1-3 h per week.

PMID- 24589032
TI  - WITHDRAWN: Corrigendum to "Screening of longevity-associated genes based on a
      comparison between dead and surviving populations"
AB  - The Publisher regrets that this article is an accidental duplication of an
      article that has already been published,
      http://dx.doi.org/10.1016/j.gene.2013.12.059. The duplicate article has therefore
      been withdrawn.

PMID- 24589031
TI  - Anti-cancer effects of Grailsine-Al-glycoside isolated from Rhizoma Sparganii.
AB  - BACKGROUND: An embryonic toxicity of Rhizoma sparganii was observed in mice. This
      study was aimed to evaluate the anticancer effects of Grailsine-Al-glycoside, the
      bioactive component of Rhizoma sparganii, on estrogen receptor-positive (ER+) and
      estrogen receptor-negative (ER-) cancer cell lines. METHODS: After A549, HeLa,
      HepG-2 and MCF-7 cells were treated with Grailsine-Al-glycoside, cell
      proliferation was analyzed by MTT, cell cycle and apoptosis by flow cytometry,
      and morphology with an immunofluorescence microscope. RESULTS: Grailsine-Al
      glycoside strongly suppressed cell proliferation in a dose-dependent fashion in
      A549, MCF-7, HepG2, and HeLa cells, though this growth inhibitory effect on HepG2
      cells was not as strong and long lasting. Compared to the control, Grailsine-Al
      glycoside caused a significant increase of apoptosis in A549, MCF-7 and Hela
      cells. A549 and MCF-7 cells were arrested at the G2/S phase whereas HepG2 cells
      were arrested at the G1 phase by a high concentration of Grailsine-Al-glycoside .
      Cell shapes were also changed by the presence of Grailsine-Al-glycoside.
      CONCLUSIONS: Grailsine-Al-glycoside from Rhizoma sparganii inhibited the
      proliferation of ER+ and some ER- cancer cells. Grailsine-Al-glycoside may be
      used as a chemotherapeutic agent against ER+ and ERRalpha-expressing ER- cancers.

PMID- 24589030
TI  - An atypical winter outbreak of hand, foot, and mouth disease associated with
      human enterovirus 71, 2010.
AB  - BACKGROUND: To analyze the epidemiological characteristics and pathogenic
      molecular characteristics of an hand, foot, and mouth disease (HFMD) outbreak
      caused by enterovirus 71 in Linyi City, Shandong Province, China during November
      30 to December 28, 2010. METHODS: One hundred and seventy three stool specimens
      and 40 throat samples were collected from 173 hospitalized cases. Epidemiologic
      and clinical investigations, laboratory testing, and genetic analyses were
      performed to identify the causal pathogen of the outbreak. RESULTS: Among the 173
      cases reported in December 2010, the male-female ratio was 1.88: 1; 23 cases
      (13.3%) were severe. The majority of patients were children aged < 5 years
      (95.4%). Some patients developed respiratory symptoms including runny nose
      (38.2%), cough (20.2%), and sore throat (14.5%). One hundred and thirty eight
      EV71 positive cases were identified based on real time reverse-transcription PCR
      detection and 107 isolates were sequenced with the VP1 region. Phylogenetic
      analysis of full-length VP1 sequences of 107 Linyi EV71 isolates showed that they
      belonged to the C4a cluster of the C4 subgenotype and were divided into 3
      lineages (Lineage I, II and III). The two amino acid substitutions (Gly and Gln
      for Glu) at position 145 within the VP1 region are more likely to appear in EV71
      isolates from severe cases (52.2%) than those recovered from mild cases (8.3%).
      CONCLUSION: This outbreak of HMFD was caused by EV71 in an atypical winter. EV71
      strains associated with this outbreak represented three separate chains of
      transmission. Substitution at amino acid position 145 of the VP1 region of EV71
      might be an important virulence marker for severe cases. These findings suggest
      that continued surveillance for EV71 variants has the potential to greatly impact
      HFMD prevention and control.

PMID- 24589033
TI  - Leukoaraiosis correlates with the neurologic deterioration after small
      subcortical infarction.
AB  - BACKGROUND: Patients of small subcortical infarction sometimes have neurologic
      deterioration (ND), with the risk factors and specific pathogenesis unclear.
      Small subcortical infarction is often accompanied by other phenotypes of small
      vessel disease such as leukoaraiosis, which indicates the white matter
      hyperintensities in the deep or periventricular areas on the fluid-attenuated
      inversion recovery series of magnetic resonance images and was proved to be
      associated with stroke in various aspects. In this study, we intended to
      investigate whether leukoaraiosis was associated with ND after small subcortical
      infarction, and explore other possible risk factors of ND. METHODS: Patients with
      single acute subcortical infarction (<1.5 cm in diameter) were recruited
      consecutively and evaluated everyday. ND was defined as worsening by 2 points or
      more in the National Institutes Health Stroke Scale (NIHSS) score, or by 1 point
      or more in the NIHSS score for motor function within 1 week after stroke onset.
      Leukoaraiosis was rated according to the age-related white matter changes scale.
      Univariate and multivariate analyses were performed to identify the risk factors
      for ND. RESULTS: Eighty-four of 435 patients (19.31%) had ND. Univariate analysis
      showed that age, severity of leukoaraiosis, baseline NIHSS score, presence of
      diabetes, hemoglobin A1c, and total cholesterol levels were all associated with
      ND. Multivariate analysis further identified that the severity of leukoaraiosis
      especially leukoaraiosis adjacent to the index infarction, baseline NIHSS score,
      and diabetes were independently associated with ND. CONCLUSIONS: Severity of
      leukoaraiosis and baseline neurologic deficits, and the presence of diabetes were
      all independently associated with ND after small subcortical infarction.

PMID- 24589034
TI  - Blood viscosity in subcortical vascular mild cognitive impairment with versus
      without cerebral amyloid burden.
AB  - BACKGROUND: Subcortical vascular dementia (SVaD) is a common form of dementia,
      attributed to ischemic small-vessel disease. Blood viscosity (BV) may contribute
      to the pathophysiology of SVaD. However, SVaD patients with coexisting amyloid
      deposition may not show differences in BV because their small-vessel disease may
      result from amyloid angiopathy independently of BV. We, therefore, hypothesized
      that BV might show different changes compared with control subjects in
      subcortical vascular mild cognitive impairment (svMCI) that refers to the
      prodromal stage of SVaD according to cerebral amyloid burden detected by the
      [(11)C] Pittsburgh compound B (PiB) PET (positron emission tomography), and
      apolipoprotein 4 (ApoE4) genotype (a known risk factor for vascular and
      parenchymal amyloid). METHODS: Our subjects consisted of 33 healthy normal
      controls (NC), 28 patients with PiB(-) svMCI, and 12 with PiB(+) svMCI. They
      underwent scanning capillary tube viscometer measuring BV during systolic and
      diastolic phases. RESULTS: Compared with the NC group, the PiB(-) svMCI group
      showed increased diastolic blood viscosity (DBV) but no difference in systolic
      blood viscosity (SBV). By contrast, there was no significant difference in SBV
      and DBV between the NC and PiB(+) svMCI groups. Within the PiB(+) svMCI group,
      ApoE4(-) subgroup showed increased DBV compared with the ApoE4(+) subgroup.
      CONCLUSIONS: Increased DBV is an important contributor to the development of
      "pure" svMCI (ie, without cerebral amyloid deposition). The relationship between
      BV and PiB(+) svMCI differed according to ApoE genotype, suggesting that the
      pathogenesis of PiB(+) svMCI might also be heterogeneous.

PMID- 24589035
TI  - The influence of neighborhood unemployment on mortality after stroke.
AB  - BACKGROUND: Few studies have investigated the impact of neighborhood
      characteristics on mortality after stroke. Aim of our study was to analyze the
      influence of district unemployment as indicator of neighborhood socioeconomic
      status (SES-NH) on poststroke mortality, and to compare these results with the
      mortality in the underlying general population. METHODS: Our analyses involve 2
      prospective cohort studies from the city of Dortmund, Germany. In the Dortmund
      Stroke Register (DOST), consecutive stroke patients (N=1883) were recruited from
      acute care hospitals. In the Dortmund Health Study (DHS), a random general
      population sample was drawn (n=2291; response rate 66.9%). Vital status was
      ascertained in the city's registration office and information on district
      unemployment was obtained from the city's statistical office. We performed
      multilevel survival analyses to examine the association between district
      unemployment and mortality. RESULTS: The association between neighborhood
      unemployment and mortality was weak and not statistically significant in the
      stroke cohort. Only stroke patients exposed to the highest district unemployment
      (fourth quartile) had slightly higher mortality risks. In the general population
      sample, higher district unemployment was significantly associated with higher
      mortality following a social gradient. After adjustment for education, health
      related behavior and morbidity was made the strength of this association
      decreased. CONCLUSIONS: The impact of SES-NH on mortality was different for
      stroke patients and the general population. Differences in the association
      between SES-NH and mortality may be partly explained by disease-related
      characteristics of the stroke cohort such as homogeneous lifestyles, similar
      morbidity profiles, medical factors, and old age.

PMID- 24589036
TI  - White matter hyperintensities in mild cognitive impairment: clinical impact of
      location and interaction with lacunes and medial temporal atrophy.
AB  - This study was to evaluate the influence on cognition and activities of daily
      living (ADL) by white matter hyperintensities (WMHs) based on the severity and
      location, as well as the interactions among WMHs, lacunes, and medial temporal
      atrophy (MTA). In 150 patients with amnestic mild cognitive impairment, WMHs were
      quantified with the use of a semiautomated volumetric method. Lacune counting and
      MTA assessment were performed by visual rating. The severer WMHs were, the more
      executive functions decreased. The influence on executive functions such as
      verbal fluency test and Stroop color reading test were greater in periventricular
      (PV) WMHs than deep WMHs, as well as bigger in anterior, middle, and posterior
      areas in order. The instrumental (I) ADL was strongly associated with the
      anterior (P = .028) and middle area (P = .014) of PVWMHs only. WMHs had
      synergistic interactions with lacunes in Controlled Oral Word Association Task
      semantic (beta = -1.12; R(2) = .24; P = .039), Stroop color (beta = -2.07; R(2) =
      .15; P = .049), and IADL (beta = .23; R(2) = .20; P = .009). Anterior PVWMHs
      demonstrated the most powerful impact on frontal executive dysfunction and poor
      performance of IADL. WMHs had synergistic effects with the number of lacunes on
      them. Therefore, it is desirable to consider WMHs and lacunes simultaneously as
      potential imaging biomarkers for predicting cognition and IADL in aMCI. 

PMID- 24589038
TI  - In vitro evaluation of the use of diluted sodium hypochlorite (bleach) against
      Staphylococcus pseudintermedius, Pseudomonas aeruginosa and Malassezia
      pachydermatis.

PMID- 24589039
TI  - Effects of the economic crisis on health and healthcare in Greece in the
      literature from 2009 to 2013: a systematic review.
AB  - BACKGROUND: Due to the current economic crisis in Greece, effects on health and
      healthcare have been reported. The aim of this study was to present a systematic
      overview of the consequences that the financial crisis has had for health and
      healthcare in Greece. METHODS: Systematic literature review was conducted in
      order to identify articles that were published from January 2009 to March 2013
      and explicitly referred to the effects of economic crisis on health or
      healthcare, in Greece. Data extraction and synthesis was performed with the use
      of thematic analysis. FINDINGS: Thirty-nine studies were considered for further
      analyses. Various existing and potential relevant effects were identified,
      including reductions in public health expenditure and changes in healthcare
      services and the pharmaceutical market, with an increasing number of admissions
      in public healthcare sector, and efficiency and organizational-related issues
      being evident, overall. Indications were found for post-crisis deterioration of
      public health with increasing rates of mental health, suicides, and epidemics,
      and deterioration of self-rated health. CONCLUSION: The recent efforts to reform
      the Greek National Health System have been focusing mainly on short-term effects
      by reducing expenditure, while the measures imposed seem to have dubious long
      term consequences for Greek public health and healthcare.

PMID- 24589037
TI  - Marine bacterioplankton community turnover within seasonally hypoxic waters of a
      subtropical sound: Devil's Hole, Bermuda.
AB  - Understanding bacterioplankton community dynamics in coastal hypoxic environments
      is relevant to global biogeochemistry because coastal hypoxia is increasing
      worldwide. The temporal dynamics of bacterioplankton communities were analysed
      throughout the illuminated water column of Devil's Hole, Bermuda during the 6
      week annual transition from a strongly stratified water column with suboxic and
      high-pCO2 bottom waters to a fully mixed and ventilated state during 2008. A
      suite of culture-independent methods provided a quantitative spatiotemporal
      characterization of bacterioplankton community changes, including both direct
      counts and rRNA gene sequencing. During stratification, the surface waters were
      dominated by the SAR11 clade of Alphaproteobacteria and the cyanobacterium
      Synechococcus. In the suboxic bottom waters, cells from the order Chlorobiales
      prevailed, with gene sequences indicating members of the genera Chlorobium and
      Prosthecochloris--anoxygenic photoautotrophs that utilize sulfide as a source of
      electrons for photosynthesis. Transitional zones of hypoxia also exhibited
      elevated levels of methane- and sulfur-oxidizing bacteria relative to the
      overlying waters. The abundance of both Thaumarcheota and Euryarcheota were
      elevated in the suboxic bottom waters (> 10(9) cells l(-1)). Following convective
      mixing, the entire water column returned to a community typical of oxygenated
      waters, with Euryarcheota only averaging 5% of cells, and Chlorobiales and
      Thaumarcheota absent.

PMID- 24589040
TI  - Behavioral addictions: a novel challenge for psychopharmacology.
AB  - Although addictive syndromes have been traditionally related to substance-use
      disorders, during the last few decades a novel addictive group, including the so
      called "behavioral or no-drug addictions," has been recognized and has attracted
      increasing attention for its relevant social impact. This group includes
      pathological gambling, compulsive shopping, TV/Internet/social network/videogame
      addictions, workaholism, sex and relationship addictions, orthorexia, and
      overtraining syndrome. Substance and behavioral addictions show similar
      phenomenological features, such as craving, dependence, tolerance, and
      abstinence, and perhaps they share a common possible pathophysiology. It is,
      however, controversial whether all or at least some of them should be considered
      real disorders or just normal, albeit extreme, behaviors. The aim of this article
      is to review current data on pharmacological treatment of behavioral addictions.
      As no specific and validated treatment algorithms are currently available, only
      an improved knowledge on their psychopathological, clinical, and neurobiological
      features may have relevant implications for more focused preventive and
      therapeutic strategies. 

PMID- 24589042
TI  - Maternal dietary fatty acid intake during pregnancy and the risk of preclinical
      and clinical type 1 diabetes in the offspring.
AB  - The aim of the present study was to examine the associations between the maternal
      intake of fatty acids during pregnancy and the risk of preclinical and clinical
      type 1 diabetes in the offspring. The study included 4887 children with human
      leucocyte antigen (HLA)-conferred type 1 diabetes susceptibility born during the
      years 1997-2004 from the Finnish Type 1 Diabetes Prediction and Prevention Study.
      Maternal diet was assessed with a validated FFQ. The offspring were observed at 3
      to 12-month intervals for the appearance of type 1 diabetes-associated
      autoantibodies and development of clinical type 1 diabetes (average follow-up
      period: 4.6 years (range 0.5-11.5 years)). Altogether, 240 children developed
      preclinical type 1 diabetes and 112 children developed clinical type 1 diabetes.
      Piecewise linear log-hazard survival model and Cox proportional-hazards
      regression were used for statistical analyses. The maternal intake of palmitic
      acid (hazard ratio (HR) 0.82, 95 % CI 0.67, 0.99) and high consumption of cheese
      during pregnancy (highest quarter v. intermediate half HR 0.52, 95 % CI 0.31,
      0.87) were associated with a decreased risk of clinical type 1 diabetes. The
      consumption of sour milk products (HR 1.14, 95 % CI 1.02, 1.28), intake of
      protein from sour milk (HR 1.15, 95 % CI 1.02, 1.29) and intake of fat from fresh
      milk (HR 1.43, 95 % CI 1.04, 1.96) were associated with an increased risk of
      preclinical type 1 diabetes, and the intake of low-fat margarines (HR 0.67, 95 %
      CI 0.49, 0.92) was associated with a decreased risk. No conclusive associations
      between maternal fatty acid intake or food consumption during pregnancy and the
      development of type 1 diabetes in the offspring were detected.

PMID- 24589044
TI  - Efficacy and cost-effectiveness of octenidine wound gel in the treatment of
      chronic venous leg ulcers in comparison to modern wound dressings.
AB  - The aim of this study was to determine the efficacy, safety and cost
      effectiveness of an octenidine-based wound gel in the treatment of chronic venous
      leg ulcers. For this purpose, 49 wounds were treated with either modern wound
      phase-adapted dressings alone (treatment arm 1; n = 17), octenidine wound gel
      plus modern wound-phase-adapted dressings (treatment arm 2; n = 17) or octenidine
      wound gel alone (treatment arm 3; n = 15). During the study period of 42 days
      with dressing changes every 3-5 days, wound healing characteristics and treatment
      costs of different dressings were analysed. Wound size reduction was
      significantly better (P = 0.028) in both octenidine wound gel treatment arms
      compared to modern dressings alone with total reductions of 14.6%, 64.1% and
      96.2% in treatment arms 1-3. Early wound healing was merely observed under
      octenidine wound gel treatment (n = 9), whereby lowest treatment costs were
      generated by octenidine wound gel alone (?20.34/dressing change). As a result,
      the octenidine wound gel is cost-effective and well suitable for the treatment of
      chronic venous leg ulcers, considering both safety and promotion of wound
      healing. 

PMID- 24589045
TI  - Reflecting.

PMID- 24589046
TI  - Promoting sexual health with SMS texting technology.
AB  - Most cell phone owners use the short message service (SMS), also known as
      "texting." Most teens and young adults use text messages; they were the first
      users to embrace this technology and are still the most frequent users. Text
      messaging has the potential to provide them with information about preventing
      sexually transmitted infections. Several innovative programs that use text
      messaging to promote sexual health are described here.

PMID- 24589043
TI  - Impact of compliance with infection management guidelines on outcome in patients
      with severe sepsis: a prospective observational multi-center study.
AB  - INTRODUCTION: Current sepsis guidelines recommend antimicrobial treatment (AT)
      within one hour after onset of sepsis-related organ dysfunction (OD) and surgical
      source control within 12 hours. The objective of this study was to explore the
      association between initial infection management according to sepsis treatment
      recommendations and patient outcome. METHODS: In a prospective observational
      multi-center cohort study in 44 German ICUs, we studied 1,011 patients with
      severe sepsis or septic shock regarding times to AT, source control, and adequacy
      of AT. Primary outcome was 28-day mortality. RESULTS: Median time to AT was 2.1
      (IQR 0.8 - 6.0) hours and 3 hours (-0.1 - 13.7) to surgical source control. Only
      370 (36.6%) patients received AT within one hour after OD in compliance with
      recommendation. Among 422 patients receiving surgical or interventional source
      control, those who received source control later than 6 hours after onset of OD
      had a significantly higher 28-day mortality than patients with earlier source
      control (42.9% versus 26.7%, P <0.001). Time to AT was significantly longer in
      ICU and hospital non-survivors; no linear relationship was found between time to
      AT and 28-day mortality. Regardless of timing, 28-day mortality rate was lower in
      patients with adequate than non-adequate AT (30.3% versus 40.9%, P < 0.001).
      CONCLUSIONS: A delay in source control beyond 6 hours may have a major impact on
      patient mortality. Adequate AT is associated with improved patient outcome but
      compliance with guideline recommendation requires improvement. There was only
      indirect evidence about the impact of timing of AT on sepsis mortality.

PMID- 24589048
TI  - Five steps to improve bedside breastfeeding care.
AB  - Best postpartum breastfeeding practices must address the caloric needs of all
      infants, including vulnerable infants, while enabling long-term, exclusive
      breastfeeding. An adequate subsequent milk supply depends on early, frequent and
      effective colostrum removal. A combination of hand expression of colostrum, spoon
      feeding and unrestricted breastfeeding provide more milk for infants and more
      stimulation for subsequent breast milk production. A sustainable, preventive
      practice model for low- and high-risk infants depends on elevating staff
      expertise and shifting the focus of lactation educators to address staff learning
      needs. We propose a five-step implementation program to achieve this.

PMID- 24589049
TI  - Identifying and applying a targeted evidence-based practice change in the
      maternal/child health inpatient setting.
AB  - As the literature on implementation research continues to expand, it's important
      to address the unique aspects and challenges of research dissemination and
      implementation in maternal/child health settings. This article describes a nurse
      initiated evidence-based practice (EBP) study on urinary catheterization at a
      labor and delivery unit in the southwestern United States. It describes
      successful strategies for implementing EBP, as well as barriers encountered, and
      provides recommendations for the facilitation of EBP in the maternal/child
      inpatient setting.

PMID- 24589050
TI  - Supporting breastfeeding to reduce newborn readmissions for hyperbilirubinemia.
AB  - Lack of breastfeeding support can result in inadequate feedings at the breast,
      putting newborns at risk for hyperbilirubinemia, severe jaundice and possible
      hospital readmission. Nurses can help prevent readmissions for hyperbilirubinemia
      by becoming educated about the risk factors for hyperbilirubinemia and by
      implementing preventive measures through improved breastfeeding support.

PMID- 24589051
TI  - Splenic artery aneurysm rupture during pregnancy.
AB  - Abdominal pain is commonly reported by women seeking care in obstetric triage,
      and although it it is often benign, careful assessment is warranted. A rare cause
      of left upper quadrant pain during pregnancy is splenic artery aneurysm rupture,
      which can result in massive hemorrhage and maternal and fetal mortality. In women
      who survive, serious complications from bleeding and multiple transfusions
      require intensive care. There have been reports in the literature of improved
      outcomes with utilization of hemostatic resuscitation protocols. Nurses and other
      healthcare providers must be prepared to support families in the aftermath of
      this critical event. This article includes a case example of splenic artery
      aneurysm rupture that resulted in perinatal loss.

PMID- 24589052
TI  - The emerging threat from carbapenem-resistant enterobacteriaceae.
AB  - The emergence of carbapenem-resistant enterobacteriaceae (CRE) in the United
      States represents a serious danger to people who are hospitalized and is
      associated with case mortality rates as high as 50 percent. CRE infections have
      limited treatment options and the potential to spread widely if prevention and
      transmission measures are not employed. Decreasing the impact of CRE requires
      coordinated efforts between nurses and other clinicians, as well as
      administrators, to improve patient outcomes.

PMID- 24589053
TI  - Allergic rhinitis, environmental triggers and treatment modalities.
AB  - Allergic rhinitis is a clinical condition with effects ranging from mildly
      bothersome to life-threatening. Women's quality of life as well as productivity
      at home, at work and in the community can be greatly affected. It's imperative
      that clinicians engage in a complete health history with each woman presenting
      with allergic rhinitis to try to identify potential environmental triggers. Once
      the allergens are identified, a multifaceted treatment plan can be devised to
      help women maintain optimal functionality.

PMID- 24589054
TI  - Walking beyond our borders with frontline health workers in Guatemala.
AB  - In many developing countries, access to health care can be out of reach for many
      women and newborns. Trained frontline health workers serve as the first point of
      contact for medical care in many of these areas, and their efforts can prevent
      illness and death from conditions such as malaria, pneumonia and diarrhea. Their
      work is especially vital to reducing maternal and newborn morbidity and
      mortality. Due to the global shortage of health workers, nurses and organizations
      need to collectively advocate for the support and training of frontline health
      workers.

PMID- 24589055
TI  - The rewards and challenges of becoming a clinical instructor.
AB  - Frontline nurses working in the clinical area are a vital component to nursing
      education. Taking on the role of adjunct clinical instructor can be a rewarding
      way to increase one's own knowledge while performing the important task of
      educating the next generation of nurses.

PMID- 24589058
TI  - A view from the bed.

PMID- 24589059
TI  - Editorial on "beyond dispersive liquid-liquid microextraction" by Mei-I Leong,
      Ming-Ren Fuh and Shang-Da Huang.

PMID- 24589060
TI  - Surgery and outcomes of six patients with intradural epidermoid cysts in the
      lumbar spine.
AB  - STUDY DESIGN: This was a retrospective study. OBJECTIVE: The aim of this study
      was to analyze the clinical characteristics and discuss the treatment options for
      epidermoid cysts in the lumbar spine. SUMMARY OF BACKGROUND DATA: Epidermoid
      cysts are rare benign neoplasms, which account for less than 1% of all
      intraspinal tumors. Due to their rarity, there are only a few case reports in the
      literature. Complete excision is the recommended treatment for an epidermoid
      cyst, but this is difficult to achieve in the spine. In spite of their benign
      nature, local recurrence is not uncommon for spinal epidermoid cysts after
      incomplete excision. METHODS: Six patients with an epidermoid cyst in the lumbar
      spine underwent surgical treatment in our center between 2004 and 2011. A total
      excision using microsurgical techniques and reconstruction was successfully
      undertaken in all patients. Clinical data and detailed pathologic results were
      retrospectively analyzed. All cases were followed up for a median time of more
      than 4 years. The clinical data and surgical efficacy were analyzed to suggest
      treatment options for epidermoid cysts in the lumbar spine on the basis of a
      literature review and our own experience. RESULTS: The mean age of the patients
      in this study was 37.7 years and the mean duration of pre-operative symptoms was
      29.7 months (2 to 120 months). All patients were disease-free during their follow
      up period. Radicular pain nearly disappeared, and patients suffering from
      neurologic deficits and defecation disorders recovered well. CONCLUSIONS:
      Although an epidermoid cyst is a benign tumor, it is apt to recur locally
      following inadequate removal. Therefore, complete excision with preservation of
      neural function is an ideal protocol for intraspinal epidermoid cysts.
      Microsurgical techniques are very useful.

PMID- 24589062
TI  - Genetic considerations in human sex-mate selection: partners share human
      leukocyte antigen but not short-tandem-repeat identity markers.
AB  - PROBLEM: Previous studies support a role for MHC on mating preference, yet it
      remains unsettled as to whether mating occurs preferentially between individuals
      sharing human leukocyte antigen (HLA) determinants or not. Investigating sex-mate
      preferences in the contemporary Israeli population is of further curiosity being
      a population with distinct genetic characteristics, where multifaceted cultural
      considerations influence mate selection. METHOD OF STUDY: Pairs of male-female
      sex partners were evaluated in three groups. Two groups represented unmarried (n
      = 1002) or married (n = 308) couples and a control group of fictitious male
      female couples. HLA and short-tandem-repeat (STR) genetic identification markers
      were assessed for the frequency of shared antigens and alleles. RESULTS: Human
      leukocyte antigen results showed that Class I and/ or Class II single antigen as
      well as double antigen sharing was more common in sex partners than in control
      group couples (P < 0.001). Married versus unmarried pairs were not
      distinguishable. In contrast, STR-DNA markers failed to differentiate between sex
      mates and controls (P = 0.78). CONCLUSION: Sex partnerships shared HLA
      determinants more frequently than randomly constituted male-female pairs. The
      observed phenomenon does not reflect a syngenetic background between sex-mates as
      STR markers were not selectively shared. Thus, sex-mate selection in man may
      contravene the evolutionary pressure for genetic diversity in regard to HLA.

PMID- 24589061
TI  - Quantification of Gram-positive bacteria: adaptation and evaluation of a
      preparation strategy using high amounts of clinical tissue.
AB  - BACKGROUND: A preparation method for quantification of bacteria in tissues is
      obligatory to reduce tissue mass, concentrate the target, purify, remove
      inhibitory substances and to achieve constant target recovery rates. No
      preparation method has been available until now for a high mass of tissue
      applicable for routine use and analytical veterinary diagnostics. RESULTS: This
      study describes an easy-to-use tissue preparation protocol to quantify Gram
      positive bacteria from a large volume of tissue matrix. A previously published
      sample preparation method (Matrix-Lysis) from food science was successfully
      adapted for clinical use on tissues from pigs, including cerebrum, spinal cord,
      lung, liver, ileum, colon, caecum, kidney and muscle tissue. This tissue
      preparation method now permits quantification of pathogens from 5 g of organic
      matrix, which is a 20-200 fold increase by weight compared to other methods. It
      is based on solubilization of the sample matrix with either a chaotrope plus
      detergent or divalent salts as solubilization agents. The method was designed as
      a modular system, offering the possibility to change lysis buffers, according to
      tissue solubilization characteristics and the intended detection method
      (molecular or culture). Using Listeria monocytogenes as model organism, viable
      cell quantification or DNA extraction and quantitative real-time PCR were
      performed after Matrix-Lysis to determine recovery rates and detection limit
      (LOD). The adapted Matrix-Lysis protocol resulted in high recovery rates (mean
      value: 76% +/- 39%) for all tested organs, except kidney, and recovery was
      constant over 5 log scales for all tested buffer systems. The LOD for Matrix
      Lysis with subsequent plate count method (PCM) was as low as 1 CFU/5 g, while for
      qPCR based detection the LOD was 102 bacterial cell equivalents (BCE)/5 g for two
      buffer systems. CONCLUSIONS: This tissue preparation is inexpensive and can be
      easily used for routine and analytical veterinary diagnostics. Inoculation
      studies or hazard assessments can profit from this tissue preparation method and
      it is anticipated that this study will be a valuable source for further research
      on tissue preparation strategies.

PMID- 24589063
TI  - Osteopetrosis.

PMID- 24589064
TI  - Rehabilitation improved walking ability for three haemophilia patients with
      inhibitors.

PMID- 24589065
TI  - Antifungal prophylaxis following heart transplantation: systematic review.
AB  - Patients with heart transplantation have a high incidence of infectious
      complications, especially fungal infections. The aim of the systematic review was
      to determine the best pharmacological strategy to prevent fungal infections among
      patients with heart transplant. We searched the PubMed and Embase databases for
      studies reporting the effectivenesss of pharmacologic strategies to prevent
      fungal infections in adult patient with a heart transplant. Our search yielded
      five studies (1176 patients), four of them with historical controls. Two studies
      used inhaled amphotericin B deoxycholate, three used itraconazole and one used
      targeted echinocandin. All studies showed significant reduction in the
      prophylaxis arm. Different products, doses and outcomes were noted. There is a
      highly probable benefit of prophylaxis use, however, better studies with
      standardised doses and comparators should be performed. 

PMID- 24589067
TI  - Evaluation of antinociceptive activity of hydromethanol extract of Cyperus
      rotundus in mice.
AB  - BACKGROUND: Cyperus rotundus Linn. (Cyperaceae) is used to treat inflammation,
      pain, fever, wounds, boils and blisters in folk medicine. This study evaluated
      the antinociceptive effect of the hydromethanol extract of whole plant of C.
      rotundus (HMCR). METHODS: The antinociceptive activity of HMCR was investigated
      in thermal-induced (hot plate and tail immersion) and chemical-induced (formalin)
      nociception models in mice at three different doses (50, 100 and 200 mg/kg;
      p.o.). Morphine sulphate (5 mg/kg, i.p.) and diclofenac sodium (10 mg/kg, i.p.)
      were used as reference analgesic agents. RESULTS: In the hot-plate and tail
      immersion tests HMCR significantly increased the latency period to the thermal
      stimuli at all the tested doses (50, 100 and 200 mg/kg) (p < 0.05). The
      significant increase in latency is clear from the observations at 60 and 90 min.
      In formalin-induced paw licking test oral administration of HMCR at 100 and 200
      mg/kg doses decreased the licking of paw in early phase. All the tested doses
      (50, 100 and 200 mg/kg) significantly decreased the licking of paw in late phase
      of the test (p < 0.001). The dose 200 mg/kg was most effective showing maximum
      percentage of inhibition of licking in both early (61.60%) and late phase
      (87.41%). CONCLUSION: These results indicate the antinociceptive effect of C.
      rotundus and suggest that this effect is mediated by both peripheral and central
      mechanisms. These results support the traditional use of this plant in different
      painful conditions.

PMID- 24589068
TI  - Brain regions associated with risk and resistance for bipolar I disorder: a voxel
      based MRI study of patients with bipolar disorder and their healthy siblings.
AB  - OBJECTIVE: Bipolar I disorder is a highly heritable disorder but not all siblings
      manifest with the illness, even though they may share similar genetic and
      environmental risk factors. Thus, sibling studies may help to identify brain
      structural endophenotypes associated with risk and resistance for the disorder.
      METHODS: Structural magnetic resonance imaging (MRI) scans were acquired for 28
      euthymic patients with bipolar disorder, their healthy siblings, and 30 unrelated
      healthy controls. Statistical Parametric Mapping 8 (SPM8) was used to identify
      group differences in regional gray matter volume by voxel-based morphometry
      (VBM). RESULTS: Using analysis of covariance, gray matter analysis of the groups
      revealed a group effect indicating that the left orbitofrontal cortex [Brodmann
      area (BA) 11] was smaller in patients with bipolar disorder than in unrelated
      healthy controls [F = 14.83, p < 0.05 (family-wise error); 7 mm(3) ]. Paired t
      tests indicated that the orbitofrontal cortex of patients with bipolar disorder
      [t = 5.19, p < 0.05 (family-wise error); 37 mm(3) ] and their healthy siblings [t
      = 3.89, p < 0.001 (uncorrected); 63 mm(3) ] was smaller than in unrelated healthy
      controls, and that the left dorsolateral prefrontal cortex was larger in healthy
      siblings than in patients with bipolar disorder [t = 4.28, p < 0.001
      (uncorrected); 323 mm(3) ] and unrelated healthy controls [t = 4.36, p < 0.001
      (uncorrected); 245 mm(3) ]. Additional region-of-interest analyses also found
      volume deficits in the right cerebellum of patients with bipolar disorder [t =
      3.92, p < 0.001 (uncorrected); 178 mm(3) ] and their healthy siblings [t = 4.23,
      p < 0.001 (uncorrected); 489 mm(3) ], and in the left precentral gyrus of
      patients with bipolar disorder [t = 3.61, p < 0.001 (uncorrected); 115 mm(3) ]
      compared to unrelated healthy controls. CONCLUSIONS: The results of this study
      suggest that a reduction in the volume of the orbitofrontal cortex, which plays a
      role in the automatic regulation of emotions and is a part of the medial
      prefrontal network, is associated with the heritability of bipolar disorder.
      Conversely, increased dorsolateral prefrontal cortex volume may be a neural
      marker of a resistance factor as it is part of a network of voluntary emotion
      regulation and balances the effects of the disrupted automatic emotion regulation
      system.

PMID- 24589070
TI  - Cardiac output calculation and three-dimensional echocardiography.
AB  - OBJECTIVE: To compare the determination of stroke volume (SV) and cardiac output
      (CO) using 2-dimensional (2D) versus 3-dimensional (3D) transesophageal
      echocardiography (TEE). DESIGN: Prospective observational study. SETTING:
      Tertiary care university hospital. PARTICIPANTS: 35 patients without structural
      valve abnormalities undergoing isolated coronary artery bypass grafting.
      INTERVENTIONS: Left ventricular outflow tract (LVOT) diameter determined with 2D
      TEE was used to estimate LVOT cross-sectional area (CSALVOT). LVOT area was
      measured directly with 3D TEE by planimetry on an en face view. SV and CO were
      calculated for both methods using the continuity equation. MEASUREMENTS AND MAIN
      RESULTS: The area of the LVOT differed significantly between methods, being
      significantly larger in the 3D method (3.57+/-0.70 cm(2)v 3.98+/-0.93 cm(2)) .
      This resulted in a 10% lower CO with the 2D method of LVOT area estimation.
      CONCLUSIONS: LVOT area is underestimated with the single- axis 2D method when
      compared with 3D planimetered area. This results in a CO that is approximately
      10% lower with the 2D method.

PMID- 24589069
TI  - The diagnostic validity of musculoskeletal ultrasound in lateral epicondylalgia:
      a systematic review.
AB  - BACKGROUND: Ultrasound is considered a reliable, widely available, non-invasive
      and inexpensive imaging technique for assessing soft tissue involvement in
      Lateral epicondylalgia. Despite the number of diagnostic studies for Lateral
      Epicondylalgia, there is no consensus in the current literature on the best
      abnormal ultrasound findings that confirm lateral epicondylalgia. METHODS:
      Eligible studies identified by searching electronic databases, scanning reference
      lists of articles and chapters on ultrasound in reference books, and consultation
      of experts in sonography. Three reviewers (VCDIII, KP, KW) independently searched
      the databases using the agreed search strategy, and independently conducted all
      stages of article selection. Two reviewers (VCDIII, KP) then screened titles and
      abstracts to remove obvious irrelevance. Potentially relevant full text
      publications which met the inclusion criteria were reviewed by the primary
      investigator (VCDIII) and another reviewer (CGS). RESULTS: Among the 15 included
      diagnostic studies in this review, seven were Level II diagnostic accuracy
      studies for chronic lateral epicondylalgia based on the National Health and
      Medical Research Council Hierarchy of Evidence. Based from the pooled sensitivity
      of abnormal ultrasound findings with homogenous results (p > 0.05), the
      hypoechogenicity of the common extensor origin has the best combination of
      diagnostic sensitivity and specificity. It is moderately sensitive [Sensitivity:
      0.64 (0.56-0.72)] and highly specific [Specificity: 0.82 (0.72-0.90)] in
      determining elbows with lateral epicondylalgia. Additionally, bone changes on the
      lateral epicondyle [Sensitivity: 0.56 (0.50-0.62)] were moderately sensitive to
      chronic LE. Conversely, neovascularity [Specificity: 1.00 (0.97-1.00)],
      calcifications [Specificity: 0.97 (0.94-0.99)] and cortical irregularities
      [Specificity: 0.96 (0.88-0.99)] have strong specificity for chronic lateral
      epicondylalgia. There is insufficient evidence supporting the use of Power
      Doppler Ultrasonogrophy, Real-time Sonoelastography and sonographic probe-induced
      tenderness in diagnosing LE. CONCLUSIONS: The use of Gray-scale Ultrasonography
      is recommended in objectively diagnosing lateral epicondylalgia. The presence of
      hypoechogenicity and bone changes indicates presence of a stressed common
      extensor origin-lateral epicondyle complex in elbows with lateral epicondylalgia.
      In addition to diagnosis, detection of these abnormal ultrasound findings allows
      localization of pathologies to tendon or bone that would assist in designing an
      appropriate treatment suited to patient's condition.

PMID- 24589071
TI  - Hemodynamic compromise due to left atrium "suction event" in a patient with
      HeartMate II ventricular assist device implantation.

PMID- 24589072
TI  - Anesthetic management of total tetralogy of Fallot repair in an adult patient
      after diagnosis by transesophageal echocardiography.

PMID- 24589073
TI  - Inhibition of Premature Ventricular Contractions by Desflurane.

PMID- 24589074
TI  - Anal incontinence and Quality of Life in late pregnancy: a cross-sectional study.
AB  - OBJECTIVE: To evaluate the association between different types of anal
      incontinence (AI) and Quality of Life (QoL) in late pregnancy. DESIGN: Cross
      sectional study. SETTING: Two maternity units in Norway 2009-2010. POPULATION:
      Primiparae aged 18 or over. METHODS: Participants answered questions about AI
      during the last 4 weeks of pregnancy on the St. Mark's score and impact of QoL in
      the Fecal Incontinence QoL score. Socioeconomic data were obtained from hospital
      records. MAIN OUTCOME MEASURES: Self-reported AI and impact on QoL. RESULTS: 1571
      primiparae responded; 573 (37%) had experienced AI during the last 4 weeks of
      pregnancy. One third of the incontinent women reported reduced QoL in the domain
      'Coping'. 'Women experiencing urgency alone reported markedly better QoL compared
      to any other AI symptoms. AI appeared to have the strongest impact on the domains
      'Coping' and 'Embarrassment'. Depression was only associated with experiencing
      the combination of all three symptoms [odds ratio (OR) 13; 95%confidence interval
      (CI) 3.2-51]. Experiencing flatus alone weekly or more was associated with the
      highest impact on 'Embarrassment' (OR 20; 95%CI 6.4-61) compared with all other
      symptoms or combination of AI symptoms, except the combination of all three AI
      symptoms. CONCLUSIONS: Between 3 and 10% of the primiparae in this material
      experienced AI to such a extent that it affected QoL. The greatest impact was
      seen in the QoL domain 'Coping'. These findings highlight the importance of an
      increased awareness of AI in late pregnancy among health professionals and the
      need to implement routine discussions about AI with expectant and new mothers.

PMID- 24589075
TI  - [Psoriasis: physiopathology and immunogenetics].
AB  - Psoriasis is a multifactorial disease that involves genetic, immunological and
      environmental factors. During the last decade, several studies by genome scan on
      families or cases/controls helped to highlight more than ten loci "PSORS" located
      on different chromosomes and containing several candidate genes. Psoriasis
      appears as a genetic disease that follows the mixed model with the involvement of
      a major gene (PSORS1) and a set of minor genes with a variable penetrance
      depending on the locus. Genetic data have focused on the involvement of the
      immune system in the pathogenesis of psoriasis. It is now accepted that psoriasis
      is an immunological disease involving the response profiles TH1 and TH17. Much
      remains to be done to better elucidate the mechanisms involved in the genesis of
      psoriatic lesions to find new therapeutic targets.

PMID- 24589077
TI  - Opioid overdose and the power of old myths: what we thought we knew, what we do
      know and why it matters.

PMID- 24589076
TI  - Is there a relationship between the presence of lung mucosa preinvasive lesions
      and lung cancer incidence? Influence of tobacco consumption.
AB  - Although studied for years, the nature of the relationships between tobacco
      consumption, bronchial preinvasive lesions and lung cancer are still not
      completely elucidated. Objectives were to determine the relationship between
      tobacco consumption and lung mucosa preinvasive and invasive lesions and to
      describe patients' evolution according to baseline characteristics. METHODS:
      Bronchial biopsy specimens were taken at six predetermined sites in 156 males,
      current smokers, aged above 18 years. Relationships between smoking
      characteristics and preinvasive lesions indexes and between baseline
      characteristics and lung cancer occurrence during a prospective follow-up were
      examined. RESULTS: Maximum grade was hyperplasia for 16.7% of patients,
      metaplasia 33.3%, dysplasia 25.0%, and carcinoma in situ 1.3%. For 23.7% of
      patients, all biopsies were considered normal. Preinvasive lesion indexes were
      related to smoking intensity (cigarettes/day). Lung cancer incidence during the
      follow-up was 19.9%. No association between severity of mucosa lesions at
      baseline and incidence of cancer during the follow-up period was observed.
      CONCLUSION: The majority of smokers had mucosa lesions, but a relatively small
      number of them would have a cancer, and there was a poor correlation between
      severity of mucosalesions and incidence of cancer. Even if an evolution from
      preinvasive lesions to an invasive cancer is plausible and coherent with current
      concepts, this link does not appear strong enough to recommend the use of
      systematic classic endoscopy for targeting of a sub-group of higher risk smokers
      who would require a closer follow up.

PMID- 24589079
TI  - Association between the microarray-based CYP2C19 genotyping assay and the
      platelet function test in cardiovascular patients receiving clopidogrel.

PMID- 24589080
TI  - Localized form of pigmented villonodular synovitis of the knee: the meniscal
      mime.
AB  - The localized form of pigmented villonodular synovitis of the knee is a rare
      condition with non-specific symptoms. This makes diagnosis especially difficult
      when the meniscus is affected. A full assessment with several imaging modalities
      can help support the preoperative diagnosis. But in the case reported here, the
      full clinical and paraclinical assessment (X-rays, CT arthrography and MRI) was
      wrong--the localized form of pigmented villonodular synovitis had mimicked a
      lateral meniscus injury and was only detected during arthroscopy. The lesion was
      excised surgically and the diagnosis was confirmed through postoperative
      histopathology.

PMID- 24589082
TI  - Staying true to the mission: adapting telepsychiatry to a new environment.

PMID- 24589083
TI  - Expression of 8-oxoguanine glycosylase in human fetal membranes.
AB  - PROBLEM: The most common DNA lesion generated by oxidative stress (OS) is 7, 8
      dihydro-8-oxoguanine (8-oxoG) whose excision repair is performed by 8-oxoguanine
      glycosylase (OGG1). We investigated OGG1 expression changes in fetal membranes
      from spontaneous preterm birth (PTB) and preterm premature rupture of the
      membranes (pPROM) and its changes in vitro in normal fetal membranes exposed to
      OS inducer water-soluble cigarette smoke extract (CSE). METHOD OF STUDY: DNA
      damage was determined in amnion cells treated with CSE by comet and FLARE assays.
      OGG1 mRNA expression and localization in fetal membranes from clinical specimens
      and in normal term membranes exposed to CSE were examined by QRT-PCR and by
      immunohistochemistry. RESULTS: DNA strand and base damage was seen in amnion
      cells exposed to CSE. OGG1 expression was 2.5-fold higher in PTB samples compared
      with pPROM (P = 0.045). No significant difference was seen between term and pPROM
      or PTB and term. CSE treatment showed a nonsignificant decrease in OGG1. OGG1 was
      localized to both amnion and chorion with less intense staining in pPROM and CSE
      treated membranes. CONCLUSION: Increased OS-induced DNA damage predominated by 8
      oxoG is likely to persist in fetal cells due to reduced availability of base
      excision repair enzyme OGG1. This can likely lead to fetal cell senescence
      associated with some adverse pregnancy outcome.

PMID- 24589081
TI  - Rescue karyotyping: a case series of array-based comparative genomic
      hybridization evaluation of archival conceptual tissue.
AB  - BACKGROUND: Determination of fetal aneuploidy is central to evaluation of
      recurrent pregnancy loss (RPL). However, obtaining this information at the time
      of a miscarriage is not always possible or may not have been ordered. Here we
      report on "rescue karyotyping", wherein DNA extracted from archived paraffin
      embedded pregnancy loss tissue from a prior dilation and curettage (D&C) is
      evaluated by array-based comparative genomic hybridization (aCGH). METHODS: A
      retrospective case series was conducted at an academic medical center. Patients
      included had unexplained RPL and a prior pregnancy loss for which karyotype
      information would be clinically informative but was unavailable. After extracting
      DNA from slides of archived tissue, aCGH with a reduced stringency approach was
      performed, allowing for analysis of partially degraded DNA. Statistics were
      computed using STATA v12.1 (College Station, TX). RESULTS: Rescue karyotyping was
      attempted on 20 specimens from 17 women. DNA was successfully extracted in 16
      samples (80.0%), enabling analysis at either high or low resolution. The longest
      interval from tissue collection to DNA extraction was 4.2 years. There was no
      significant difference in specimen sufficiency for analysis in the collection-to
      extraction interval (p=0.14) or gestational age at pregnancy loss (p=0.32). Eight
      specimens showed copy number variants: 3 trisomies, 2 partial chromosomal
      deletions, 1 mosaic abnormality and 2 unclassified variants. CONCLUSIONS: Rescue
      karyotyping using aCGH on DNA extracted from paraffin-embedded tissue provides
      the opportunity to obtain critical fetal cytogenetic information from a prior
      loss, even if it occurred years earlier. Given the ubiquitous archiving of
      paraffin embedded tissue obtained during a D&C and the ease of obtaining results
      despite long loss-to-testing intervals or early gestational age at time of fetal
      demise, this may provide a useful technique in the evaluation of couples with
      recurrent pregnancy loss.

PMID- 24589078
TI  - Maternal race, demography, and health care disparities impact risk for
      intraventricular hemorrhage in preterm neonates.
AB  - OBJECTIVE: To determine whether risk factors associated with grade 2-4
      intraventricular hemorrhage (IVH) differs between infants of African ancestry and
      white infants. STUDY DESIGN: Inborn, appropriate for gestational age infants with
      birth weight 500-1250 g and exposure to at least 1 dose of antenatal steroids
      were enrolled in 24 neonatal intensive care units. Cases had grade 2-4 IVH and
      controls matched for site, race, and birth weight range had 2 normal ultrasounds
      read centrally. Multivariate logistic regression modeling identified factors
      associated with IVH across African ancestry and white race. RESULTS: Subjects
      included 579 African ancestry or white race infants with grade 2-4 IVH and 532
      controls. Mothers of African ancestry children were less educated, and white case
      mothers were more likely to have more than 1 prenatal visit and multiple
      gestation (P <= .01 for all). Increasing gestational age (P = .01), preeclampsia
      (P < .001), complete antenatal steroid exposure (P = .02), cesarean delivery (P <
      .001), and white race (P = .01) were associated with decreased risk for IVH.
      Chorioamnionitis (P = .01), 5-minute Apgar score <3 (P < .004), surfactant use (P
      < .001), and high-frequency ventilation (P < .001) were associated with increased
      risk for IVH. Among African ancestry infants, having more than 1 prenatal visit
      was associated with decreased risk (P = .02). Among white infants, multiple
      gestation was associated with increased risk (P < .001), and higher maternal
      education was associated with decreased risk (P < .05). CONCLUSION: The risk for
      IVH differs between infants of African ancestry and white infants, possibly
      attributable to both race and health care disparities.

PMID- 24589084
TI  - Prophylaxis with anti-inhibitor coagulant complex improves health-related quality
      of life in haemophilia patients with inhibitors: results from FEIBA NF
      Prophylaxis Study.
AB  - The Pro-FEIBA study reported health-related quality of life (HRQoL) improved
      following 6-month of Factor Eight Inhibitor Bypassing Activity (FEIBA)
      prophylaxis. This study investigates whether 12-month of FEIBA prophylaxis
      improved HRQoL in haemophilia patients with inhibitors. Thirty-six subjects in a
      1-year prospective, randomized, open-label, parallel-design study were randomized
      to prophylaxis (85 +/- 15 U kg(-1) every other day) or on-demand treatment. HRQoL
      was assessed at screening, 6 and 12-month termination using the EQ-5D, Haem-A
      QoL, Haemo-QoL and a general pain visual analog scale (VAS). To evaluate changes,
      paired t-tests and criteria for minimally important differences were applied.
      Repeated measures regression tested the association between annualized bleeding
      rate (ABR) and physical HRQoL. At 6 and 12 months, prophylaxis subjects reported
      clinically meaningful improvement in EQ-5D index (mean improvement, 0.10 and
      0.08, respectively) and both clinically meaningful and statistically significant
      improvements in EQ-VAS scores (16.9 and 15.7, respectively; P < 0.05) vs.
      baseline. General pain was significantly reduced during prophylaxis at each
      follow-up (mean improvement, 20.3 and 23.2, respectively; both P <0.05). At 12
      months, prophylaxis subjects achieved significant improvements in Haem-A-QoL
      Total Score and in four domains: Physical Health, Feeling, View, and Work and
      School (all P < 0.05). No statistically significant changes, except for Haem-A
      QoL Physical Health at 6 months, were observed with on-demand treatment. ABR was
      decreased by 72.5% with prophylaxis vs. on-demand treatment (P = 0.0003) and
      reduced ABR was associated with better physical HRQoL (P < 0.05). FEIBA
      prophylaxis significantly reduced ABR and improved HRQoL in inhibitor patients.
      Subjects with lower ABR reported better physical HRQoL. 

PMID- 24589085
TI  - Rhodotorula glutinis meningitis: a case report and review of literature.
AB  - Rhodotorula is ubiquitous saprophytic yeast belonging to phylum Basidiomycota.
      These encapsulated basidiomycetes are being increasingly recognised as important
      emerging human pathogens. There are scanty reports of meningitis caused by
      Rhodurorula spp in HIV infected patients. We present one such case of meningitis
      by Rhodutorula glutinis in HIV-infected patient. The patient also had a past
      history of abdominal tuberculosis. The diagnosis of Rhodotorula was confirmed by
      Gram staining and culture of the cerebrospinal fluid (CSF). Contamination was
      ruled out by repeated culturing of CSF from the same patient. Therapy with
      Amphotericin B showed good results. Patient was discharged from the hospital.
      However, in the seventh month of follow-up patient was readmitted with complaints
      of fever, breathlessness, altered sensorium, vomiting and succumbed to his
      illness. This time the CSF cultures remained negative for Rhodotorula, acid fast
      bacilli and other pyogenic organisms. Our last 11-year retrospective analysis of
      8197 specimens received for mycological work-up showed that this is the first
      report of R. glutinis isolation from our institute. 

PMID- 24589086
TI  - Photoactivation approaches reveal a role for Rab11 in FGFR4 recycling and
      signalling.
AB  - Fibroblast growth factor receptor 4 (FGFR4) plays important roles during
      development and in the adult to maintain tissue homeostasis. Moreover,
      overexpression of FGFR4 or activating mutations in FGFR4 has been identified as
      tumour-promoting events in several forms of cancer. Endocytosis is important for
      regulation of signalling receptors and we have previously shown that FGFR4 is
      mainly localized to transferrin-positive structures after ligand-induced
      endocytosis. Here, using a cell line with a defined pericentriolar endocytic
      recycling compartment, we show that FGFR4 accumulates in this compartment after
      endocytosis. Furthermore, using classical recycling assays and a new,
      photoactivatable FGFR4-PA-GFP fusion protein combined with live-cell imaging, we
      demonstrate that recycling of FGFR4 is dependent on Rab11. Upon Rab11b depletion,
      FGFR4 is trapped in the pericentriolar recycling compartment and the total levels
      of FGFR4 in cells are increased. Moreover, fibroblast growth factor 1 (FGF1)
      induced autophosphorylation of FGFR4 as well as phosphorylation of phospholipase
      C (PLC)-gamma is prolonged in cells depleted of Rab11. Interestingly, the
      activation of mitogen-activated protein kinase and AKT pathways were not
      prolonged but rather reduced in Rab11-depleted cells, indicating that recycling
      of FGFR4 is important for the nature of its signalling output. Thus, Rab11
      dependent recycling of FGFR4 maintains proper levels of FGFR4 in cells and
      regulates FGF1-induced FGFR4 signalling. 

PMID- 24589087
TI  - Baccalaureate nursing students' perspectives on learning about caring in China: a
      qualitative descriptive study.
AB  - BACKGROUND: The need to provide humanistic care in the contemporary healthcare
      system is more imperative now and the importance of cultivating caring in nursing
      education is urgent. Caring as the primary work of nursing has been discussed
      extensively, such as the meaning of caring, and teaching and learning strategies
      to improve nursing students' caring ability. Yet attempts to understand students'
      perspectives on learning about caring and to know their learning needs are seldom
      presented. The aim of this qualitative descriptive study was to explore the
      baccalaureate nursing students' perspectives on learning about caring in China.
      METHODS: A qualitative descriptive study using focus group interviews were
      undertaken in two colleges in Yunnan Province, China from February 2010 to April
      2010. Purposeful sampling of 20 baccalaureate nursing students were recruited.
      Content analysis of the transcribed data was adopted to identify the themes.
      RESULTS: Four categories with some sub-categories related to students'
      perspectives on learning about caring were identified from the data: 1) Learning
      caring by role model; 2) conducive learning environment as the incentive to the
      learning about caring; 3) lack of directive substantive way of learning as the
      hindrance to the learning about caring; 4) lack of cultural competency as the
      barrier to the learning about caring. CONCLUSIONS: Both caring and uncaring
      experiences can promote the learning about caring in a way of reflective
      practice. The formal, informal and hidden curricula play an important role in the
      learning about caring. Cultural awareness, sensitivity and humility are important
      in the process of learning to care in a multicultural area.

PMID- 24589089
TI  - Use of tissue plasminogen activator to resolve high purge system pressure in a
      catheter-based ventricular-assist device.

PMID- 24589090
TI  - Preoperative immunonutrition decreases postoperative complications by modulating
      prostaglandin E2 production and T-cell differentiation in patients undergoing
      pancreatoduodenectomy.
AB  - BACKGROUND: An immune-enhancing diet has been used to alter eicosanoid synthesis,
      cytokine production, and immune function in an attempt to limit the undesired
      immune reactions after injury from surgery. This prospective randomized study was
      designed to investigate the effect of preoperative immunonutrition on operative
      complications, and the participation of prostaglandin E2 (PGE2) on T-cell
      differentiation in patients undergoing a severely stressful surgery. METHODS: The
      enrolled patients who were scheduled to undergo pancreatoduodenectomy were
      randomized into two groups. Patients in the immunonutrition group (n = 25)
      received oral supplementation containing arginine, omega-3 fatty acids, and RNA
      for 5 days before the procedure in addition to a 50% reduction in the amount of
      regular food. Patients in the control group (n = 25) received no artificial
      nutrition and were allowed to consume regular food before surgery. All patients
      received early postoperative enteral infusion of a standard formula intended to
      provide 25 kcal/kg/day. The primary endpoint was the rate of infectious
      complications; the secondary endpoint was immune responses. This study is
      registered with ClinicalTrials.gov (NCT01256034). RESULTS: Infectious
      complication rate and severity of complications (Clavien-Dindo classification)
      were lesser in the immunonutrition group than in the control group. mRNA
      expression levels of T-bet were greater in the immunonutrition group than in the
      control group (P < .05). Serum eicosapentaenoic acid and eicosapentaenoic
      acid/arachidonic acid ratios were greater in the immunonutrition group than in
      the control group (P < .05). The levels of plasma PGE2 were lesser in the
      immunonutrition group than in the control group (P < .05). CONCLUSION:
      Preoperative immunonutrition modulates PGE2 production and T-cell differentiation
      and may protect against the aggravation of operative complications in patients
      undergoing pancreatoduodenectomy.

PMID- 24589091
TI  - Testing for antiphospholipid antibodies with solid phase assays: guidance from
      the SSC of the ISTH.

PMID- 24589092
TI  - Restrictions in pub closing times and lockouts in Newcastle, Australia five years
      on.
AB  - INTRODUCTION AND AIMS: In 2008 pub closing times were restricted from 5 am to
      3:30 am in the central business district (CBD) of Newcastle, Australia. A
      previous study showed a one-third reduction in assaults in the 18 months
      following the restriction. We assessed whether the assault rate remained lower
      over the following 3.5 years and whether the introduction of a 'lockout' in
      nearby Hamilton was associated with a reduction in assaults there. DESIGN AND
      METHODS: We used a pre-post design with comparison against two post-change
      periods. The setting was Greater Newcastle (population 530,000) and subjects were
      persons apprehended for assault in the CBD and nearby Hamilton, an area with late
      trading pubs where a lockout and other strategies were implemented in 2010. Cases
      were police-recorded assault apprehensions occurring from 10 pm to 6 am in one
      pre-change period: January 2001 to March 2008, and two post-change periods: (i)
      April 2008 to September 2009 and (ii) October 2009 to March 2013. Negative
      binomial regression with terms for secular trend and seasonal effects was used to
      estimate Post1: Pre and Post2: Pre Incidence Rate Ratios and confidence
      intervals. RESULTS: In the CBD recorded assaults fell from 99/quarter before the
      restriction to 68/quarter in the first post-change period [incidence rate ratio
      (IRR) 0.67, 95% confidence interval (CI) 0.55-0.82] and 71/quarter (IRR: 0.68,
      95% CI: 0.55-0.85) in the later post-change period. In the same periods in
      Hamilton, assault rates were 23, 24, and 22 per quarter respectively. DISCUSSION
      AND CONCLUSIONS: The restriction in closing time was associated with a sustained
      lower assault rate in the Newcastle CBD. We find no evidence that lockouts and
      other outlet management strategies were effective in Hamilton.

PMID- 24589094
TI  - Special issue: Emerging and re-emerging epidemics affecting global health.
      Editorial.

PMID- 24589093
TI  - A novel SMARCAL1 mutation associated with a mild phenotype of Schimke immuno
      osseous dysplasia (SIOD).
AB  - BACKGROUND: Schimke immuno-osseous dysplasia (SIOD, OMIM #242900) is an autosomal
      recessive pleiotropic disorder characterized by spondyloepiphyseal dysplasia,
      renal dysfunction and T-cell immunodeficiency. SIOD is caused by mutations in the
      gene SMARCAL1. CASE PRESENTATION: We report the clinical and genetic diagnosis of
      a 5-years old girl with SIOD, referred to our Center because of nephrotic-range
      proteinuria occasionally detected during the follow-up for congenital
      hypothyroidism. Mutational analysis of SMARCAL1 gene was performed by polymerase
      chain reaction (PCR) and bidirectional sequencing. Sequence analysis revealed
      that patient was compound heterozygous for two SMARCAL1 mutations: a novel
      missense change (p.Arg247Pro) and a well-known nonsense mutation (p.Glu848*).
      CONCLUSION: This report provided the clinical and genetic description of a mild
      phenotype of Schimke immuno-osseous dysplasia associated with nephrotic
      proteinuria, decreasing after combined therapy with ACE inhibitors and sartans.
      Our experience highlighted the importance of detailed clinical evaluation,
      appropriate genetic counseling and molecular testing, to provide timely treatment
      and more accurate prognosis.

PMID- 24589095
TI  - Dedication of the 11th Biennial Meeting of the Society of Tropical Veterinary
      Medicine (STVM) Dr. Jean-Charles Maillard Orvieto, Italy, September 2012.

PMID- 24589096
TI  - The components of 'One World - One Health' approach.
AB  - The interaction between living beings, including men, animals and pathogens,
      sharing the same environment, should be considered as a unique dynamic system, in
      which the health of each component is inextricably interconnected and dependent
      with the others. Nowadays, a new integrated One Health approach is reflecting
      this interdependence with a holistic view to the ecological system. The One
      Health approach can be defined as a collaborative and a multidisciplinary effort
      at local, national and global level to guarantee an optimal healthy status for
      humans, animals and environment. Strictly related to the One Health concept is to
      be considered the control of infectious diseases, which have influenced the
      course of human history. Four different components might be identified as key
      elements within the 'One World - One Health' (OWOH) approach: the geographical
      component, the ecological one, the human activities and the food-agricultural
      ones. 

PMID- 24589097
TI  - A geographical information system-based multicriteria evaluation to map areas at
      risk for Rift Valley fever vector-borne transmission in Italy.
AB  - Rift Valley fever (RVF) is a severe mosquito-borne disease that is caused by a
      Phlebovirus (Bunyaviridae) and affects domestic ruminants and humans. Recently,
      its distribution widened, threatening Europe. The probability of the introduction
      and large-scale spread of Rift Valley fever virus (RVFV) in Europe is low, but
      localized RVF outbreaks may occur in areas where populations of ruminants and
      potential vectors are present. In this study, we assumed the introduction of the
      virus into Italy and focused on the risk of vector-borne transmission of RVFV to
      three main European potential hosts (cattle, sheep and goats). Five main
      potential mosquito vectors belonging to the Culex and Aedes genera that are
      present in Italy were identified in a literature review. We first modelled the
      geographical distribution of these five species based on expert knowledge and
      using land cover as a proxy of mosquito presence. The mosquito distribution maps
      were compared with field mosquito collections from Italy to validate the model.
      Next, the risk of RVFV transmission was modelled using a multicriteria evaluation
      (MCE) approach, integrating expert knowledge and the results of a literature
      review on host sensitivity and vector competence, feeding behaviour and
      abundance. A sensitivity analysis was performed to assess the robustness of the
      results with respect to expert choices. The resulting maps include (i) five maps
      of the vector distribution, (ii) a map of suitable areas for vector-borne
      transmission of RVFV and (iii) a map of the risk of RVFV vector-borne
      transmission to sensitive hosts given a viral introduction. Good agreement was
      found between the modelled presence probability and the observed presence or
      absence of each vector species. The resulting RVF risk map highlighted strong
      spatial heterogeneity and could be used to target surveillance. In conclusion,
      the geographical information system (GIS)-based MCE served as a valuable
      framework and a flexible tool for mapping the areas at risk of a pathogen that is
      currently absent from a region. 

PMID- 24589098
TI  - Generation and characterization of monoclonal antibodies against Rift Valley
      fever virus nucleoprotein.
AB  - Due to the unpredictable and explosive nature of Rift Valley fever (RVF)
      outbreaks, rapid and accurate diagnostic assays for low-resource settings are
      urgently needed. To improve existing diagnostic assays, monoclonal antibodies
      (MAbs) specific for the nucleocapsid protein of RVF virus (RVFV) were produced
      and characterized. Four IgG2a MAbs showed specific binding to denatured
      nucleocapsid protein, both from a recombinant source and from inactivated RVFV,
      in Western blot analysis and in an enzyme-linked immunosorbent assay (ELISA).
      Cross-reactivity with genetically related and non-related arboviruses including
      Bunyamwera and Calovo viruses (Bunyaviridae family), West Nile and Dengue-2
      viruses (Flaviviridae family), and Sindbis and Chikungunya viruses (Togaviridae
      family) was not detected. These MAbs represent a useful tool for the development
      of rapid diagnostic assays for early recognition of RVF. 

PMID- 24589099
TI  - Molecular and serological studies on the Rift Valley fever outbreak in Mauritania
      in 2010.
AB  - Rift Valley fever virus (RVFV) is a vector-borne RNA virus affecting humans,
      livestock and wildlife. In October/November 2010, after a period of unusually
      heavy rainfall, a Rift Valley fever outbreak occurred in northern Mauritania
      causing clinical cases in cattle, sheep, goats and camels, 21 of which were of
      lethal outcome. The aim of this study was to obtain further information on the
      continuation of RVF virus activity and spread in animal species in Mauritania
      after this outbreak. We therefore tested sera from small ruminants, cattle and
      camels for the presence of viral RNA and antibodies against RVFV. These sera were
      collected in different parts of the country from December 2010 to February 2011
      and tested with three different ELISAs and an indirect immunofluorescence assay.
      The results show a high seroprevalence of RVFV IgM and IgG antibodies of about
      57% in all animals investigated. Moreover, in four camel sera, viral RNA was
      detected emphasizing the important role camels played during the latest RVF
      outbreak in Mauritania. The study demonstrates the continuous spread of RVFV in
      Mauritania after initial emergence and highlights the potential role of small
      ruminants and camels in virus dissemination. 

PMID- 24589100
TI  - Analysis of surveillance systems in place in European Mediterranean countries for
      West Nile virus (WNV) and Rift Valley fever (RVF).
AB  - West Nile virus (WNV) and Rift Valley fever virus (RVFV) represent an important
      group of viral agents responsible for vector-borne zoonotic diseases constituting
      an emerging sanitary threat for the Mediterranean Basin and the neighbouring
      countries. WNV infection is present in several Mediterranean countries, whereas
      RVF has never been introduced into Europe, but it is considered a major threat
      for North African countries. Being vector-borne diseases, they cannot be
      prevented only through an animal trade control policy. Several approaches are
      used for the surveillance of WNV and RVFV. With the aim of assessing the
      surveillance systems in place in Mediterranean countries, two disease-specific
      questionnaires (WNV, RVFV) have been prepared and submitted to Public Health and
      Veterinary Authorities of six EU countries. This study presents the information
      gathered through the questionnaires and describes some critical points in the
      prevention and surveillance of these diseases as emerged by the answers received.

PMID- 24589101
TI  - Indigenous West Nile virus infections in horses in Albania.
AB  - Serum samples collected from 167 equines of 12 districts in Albania were tested
      for West Nile virus-specific antibodies by enzyme-linked immunosorbent assay and
      virus neutralization assay, using WNV lineage 1 and 2. In addition, 95 bird serum
      samples from Albania and 29 horse samples from Kosovo were tested in ELISA. An
      overall seroprevalence rate of 22% was found in horses from Albania, whereas no
      specific antibodies were found in the equine samples from Kosovo and the bird
      samples. This is the first report indicating WNV infections in animals in
      Albania, and the first reported seroprevalence study conducted for Kosovo. These
      results provide evidence for widespread infections of WNV in Albania. 

PMID- 24589102
TI  - Setting up a SPF chicken model for the pathotyping of West Nile virus (WNV)
      strains.
AB  - Birds play a central role in WNV epidemiology by spreading and amplifying the
      virus. Increasing numbers of WNV isolates are detected in Europe, and the
      virulence of these genetically variable isolates is not well characterized for
      birds. Therefore, we investigated whether SPF chickens could be a valuable avian
      model for the pathotyping of WNV strains. One-day-old SPF chickens were
      inoculated subcutaneously (SC) or intracerebrally (IC) with four lineage 1 WNV
      strains (Is98, It2008, Fr2000 or Kunjin) and were daily clinically monitored for
      2 weeks after infection. Additionally, one-day-old SPF chickens were SC
      inoculated, and one-week-old SPF chickens were SC or IC inoculated with two Euro
      Mediterranean isolates, Is98 and Fr2000, to sample blood and feathers at regular
      time points. These samples were analysed by WN NS2a-specific rRT-PCR and WN NS1
      antigen-capture ELISA that were developed for the purpose of this study.
      Differences in strain virulence were evidenced after IC inoculation of one-day
      old SPF chickens, with Is98 eliciting the highest mortality rates and Kunjin the
      lowest ones, while lethality of Fr2000 and It2008 was intermediate. Neither viral
      load in sera and feathers nor NS1 antigen in the serum correlated with the
      differential pathogenicity of Is98 and Fr2000. However, irrespective of the
      inoculated strain, younger chickens showed higher and longer-lasting viremias
      than older chickens. In all experimental groups, the detection window for viral
      RNA in feathers lasted up to 14 dpi. Altogether, the data presented in this study
      show that WNV strain virulence can be discriminated in a one-day-old SPF chicken
      model on the basis of mortality rates, while viremia and viral load in feathers
      appear to be age dependent rather than strain dependent.

PMID- 24589103
TI  - Virus excretion and antibody dynamics in goats inoculated with a field isolate of
      peste des petits ruminants virus.
AB  - A field isolate of peste des petits ruminants virus (PPRV) from an outbreak in
      Tibet, China, was inoculated into goats to investigate the dynamics of virus
      excretion and antibody production. Further, animals received PPRV vaccine strain
      Nigeria 75/1. Ocular, nasal and oral samples were tested for the presence of
      virus antigen by one-step real-time qualitative RT-PCR (qRT-PCR); competitive
      ELISA (c-ELISA) was used for the measurement of specific antibodies against PPRV.
      Virus particles could be detected as early as day 3 post-inoculation (pi) and
      virus excretion lasted for up to day 26 pi. All four goats inoculated with the
      PPRV field isolate were seropositive as early as day 10 pi. In animals inoculated
      with the vaccine strain, antibody was detected at day 14 pi, and levels of
      neutralizing antibodies remained above the protection threshold level (1 : 8) for
      8 months. Both virus particles and neutralizing antibodies were detected earlier
      in goats challenged with the field isolate than in those receiving the vaccine
      strain.

PMID- 24589104
TI  - Virulence genes and genetic diversity of Streptococcus suis serotype 2 isolates
      from Thailand.
AB  - Isolates of Streptococcus suis from different Western countries as well as those
      from China and Vietnam have been previously well characterized. So far, the
      genetic characteristics and relationship between S. suis strains isolated from
      both humans and pigs in Thailand are unknown. In this study, a total of 245 S.
      suis isolates were collected from both human cases (epidemic and sporadic) and
      pigs (diseased and asymptomatic) in Thailand. Bacterial strains were identified
      by biochemical tests and PCR targeting both, the 16S rRNA and gdh genes. Thirty
      six isolates were identified as serotype 2 based on serotyping and the cps2-PCR.
      These isolates were tested for the presence of six virulence-associated genes: an
      arginine deiminase (arcA), a 38-kDa protein and protective antigen (bay046), an
      extracellular factor (epf), an hyaluronidase (hyl), a muramidase-released protein
      (mrp) and a suilysin (sly). In addition, the genetic diversities of these
      isolates were studied by RAPD PCR and multilocus sequence typing (MLST) analysis.
      Four virulence-associated gene patterns (VAGP 1 to 4) were obtained, and the
      majority of isolates (32/36) carried all genes tested (VAGP1). Each of the three
      OPB primers used provided 4 patterns designated RAPD-A to RAPD-D. Furthermore,
      MLST analysis could also distinguish the 36 isolates into four sequence types
      (STs): ST1 (n = 32), ST104 (n = 2), ST233 (n = 1) and a newly identified ST,
      ST336 (n = 1). Dendrogram constructions based on RAPD patterns indicated that S.
      suis serotype 2 isolates from Thailand could be divided into four groups and that
      the characteristics of the individual groups were in complete agreement with the
      virulence gene profiles and STs. The majority (32/36) of isolates recovered from
      diseased pigs, slaughterhouse pigs or human patients could be classified into a
      single group (VAGP1, RAPD-A and ST1). This genetic information strongly suggests
      the transmission of S. suis isolates from pigs to humans in Thailand. Our
      findings are the first to report genetic characteristics of strains from Thailand
      and to elucidate the genetic relationship among S. suis isolates from human and
      pig origins.

PMID- 24589105
TI  - Detection of natural killer T cells in mice infected with Rickettsia conorii.
AB  - Little information is available regarding the role of natural killer T (NKT)
      cells during the early stage of Rickettsia conorii infection. Herein, C3H/HeN
      mice were infected with the Malish 7 strain of R. conorii. Splenocytes from these
      mice were analysed in the early stage of the infection by flow cytometry and
      compared with uninfected controls. Our results showed an increase in NKT cells in
      infected mice. Additionally, NKT interleukin (IL)-17(+) cells increased three
      days after infection, together with a concurrent decrease in the relative amount
      of NKT interferon (IFN)-gamma(+) cells. We also confirmed a higher amount of NK
      IFN-gamma(+) cells in infected mice. Taken together, our data showed that NKT
      cells producing Il-17 increased during the early stage of rickettsial infection.
      These results suggest a connection between IL-17(+) NKT cells and vasculitis,
      which is the main clinical symptom of rickettsiosis.

PMID- 24589106
TI  - In vitro culture of a novel genotype of Ehrlichia sp. from Brazil.
AB  - Ehrlichiae are obligate intracytoplasmic Gram-negative, tick-borne bacteria
      belonging to the Anaplasmataceae family. Ehrlichioses are considered emerging
      diseases in both humans and animals. Several members of the genus Ehrlichia have
      been isolated and propagated in vitro. This study describes the continuous
      propagation of a Brazilian Ehrlichia sp. isolate in IDE8 tick cells, canine DH82
      cells and bovine aorta cells. Initially, the organisms were isolated from the
      haemolymph of a Rhipicephalus (Boophilus) microplus tick into IDE8 cells.
      Infected IDE8 cells were brought from Brazil to Germany, where the organisms were
      continuously propagated in IDE8, DH82 and bovine aorta cells. Bovine aorta cells
      were infected and propagated for 3 months, corresponding to six subcultures,
      whereas the other two infected cell lines were kept for more than 1 year. During
      the cultivation period, 36 and 14 subcultures were carried out in IDE8 and DH82
      cell cultures, respectively. Reinfection of IDE8 cells with organisms grown in
      DH82 cells was achieved. Sequence analysis made with a fragment of the 16S rRNA
      gene showed that this Ehrlicha sp. is closely related to Ehrlichia canis.
      However, the maximum likelihood phylogenetic tree shows that it falls in a
      separate phylogenetic clade from E. canis.

PMID- 24589107
TI  - Demonstration of transplacental transmission of a human isolate of Anaplasma
      phagocytophilum in an experimentally infected sheep.
AB  - Anaplasma phagocytophilum, first identified as a pathogen of sheep in Europe,
      more recently has been recognized as an emerging tick-borne pathogen of humans in
      the U.S. and Europe. Transmission of A. phagocytophilum is reported to be by
      ticks, primarily of the genus Ixodes. While mechanical and transplacental
      transmission of the type genus organism, A. marginale, occur in addition to tick
      transmission, these modes of transmission have not been considered for A.
      phagocytophilum. Recently, we developed a sheep model for studying host-tick
      pathogen interactions of the human NY-18 A. phagocytophilum isolate. Sheep were
      susceptible to infection with this human isolate and served as a source of
      infection for I. scapularis ticks, but they did not display clinical signs of
      disease, and the pathogen was not apparent in stained blood smears. In the course
      of these experiments, one sheep unexpectedly gave birth to a lamb 5 weeks after
      being experimentally infected by inoculation with the pathogen propagated in HL
      60 cells. The lamb was depressed and not feeding and was subsequently euthanized
      18 h after birth. Tissues were collected at necropsy for microscopic examination
      and PCR to confirm A. phagocytophilum infection. At necropsy, the stomach
      contained colostrum, the spleen was moderately enlarged and thickened with
      conspicuous lymphoid follicles, and mesenteric lymph nodes were mildly enlarged
      and contained moderate infiltrates of eosinophils and neutrophils. Blood, spleen,
      heart, skin and cervical and mesenteric lymph nodes tested positive for A.
      phagocytophilum by PCR, and sequence analysis confirmed that the lamb was
      infected with the NY-18 isolate. Transplacental transmission should therefore be
      considered as a means of A. phagocytophilum transmission and may likely
      contribute to the epidemiology of tick-borne fever in sheep and other mammals,
      including humans.

PMID- 24589108
TI  - Cross-protection between geographically distinct Anaplasma marginale isolates
      appears to be constrained by limited antibody responses.
AB  - The rickettsia Anaplasma marginale causes the haemolytic disease bovine
      anaplasmosis, an economic problem in tropical and subtropical areas worldwide.
      The closely related but less pathogenic Anaplasma centrale is commonly used as a
      live vaccine to prevent anaplasmosis, but it can only be produced from infected
      blood. UFMG1 is a low pathogenic Brazilian strain of A. marginale, which has been
      shown to protect cattle against a high pathogenic Brazilian isolate. As UFMG1 can
      be grown in tick cells, the strain was proposed as a possible cell culture
      derived vaccine. We have evaluated whether UFMG1 could protect cattle against a
      geographically distant heterologous strain, using A. centrale vaccination as a
      standard for comparison. Trial calves were infected with UFMG1, A. centrale or
      PBS. UFMG1-infected animals were more symptomatic than those infected with A.
      centrale, but none required treatment. All calves were then challenged with the
      Israeli A. marginale Gonen strain (one of the most prevalent strain in Israel).
      The A. centrale group had the mildest symptoms, while UFMG1 and control groups
      both had a more severe response. Nevertheless, the challenge did not cause life
      threatening disease in any group. Animals infected with A. centrale had a
      significantly higher IgG response than UFMG1, when measured in an ELISA against
      initial bodies from their homologous strain or Gonen. The level of cross
      reactivity of the response to initial infection correlated significantly with
      reduced symptoms after challenge. In conclusion, UFMG1 had limited effect in
      preventing disease by the geographically distant heterologous Gonen strain. While
      the low pathogenicity of the Gonen strain in this trial makes it impossible to
      conclusively state that UFMG1 would have given no protective effect against more
      serious disease, the comparatively low IgG response to UFMG1 suggests it would
      not have been as effective as A. centrale. 

PMID- 24589109
TI  - Can Anaplasma ovis in small ruminants be neglected any longer?
AB  - Anaplasma species are obligate intracellular rickettsial pathogens transmitted by
      ticks with an impact on human and animal health. Anaplasma ovis infects sheep and
      goats in many regions of the world, and it can be diagnosed by different methods
      like Giemsa staining, PCR or competitive ELISA. In this study, a PCR based on the
      gene coding for major surface protein 4 (MSP-4) was used to examine field samples
      collected from sheep in different countries. Altogether, 1161 blood samples from
      Turkey (n = 830), Iraq (n = 195), Sudan (n = 96) and Portugal (n = 40) were
      examined, of which 31.4%, 66.6% 41.6% and 82.5%, respectively, were positive.
      This indicates high prevalence of A. ovis in the countries under investigation,
      and it can be assumed that the situation in other areas of the world might be
      similar. Thus, A. ovis should be considered as an important constraint of
      livestock production, and further efforts are needed to better understand the
      epidemiology and to implement suitable control measures.

PMID- 24589110
TI  - Coinfection of sheep with Anaplasma, Theileria and Babesia species in the
      Kurdistan Region, Iraq.
AB  - Infections of small ruminants with Anaplasma, Theileria and Babesia species are
      widely distributed in the old world and are of great economic impact. In Iraq,
      data on disease occurrence in sheep caused by above-mentioned infectious agents
      are scarce. This study provides information on various haemoparasitic agents
      infecting sheep in the Kurdistan Region, Iraq, using molecular diagnostic tools.
      Altogether, 195 samples originating from three governorates in the Kurdistan
      Region, namely Duhok, Erbil and Sulaimaniya, were analysed. The following
      pathogens were identified: Anaplasma ovis (62.6%), Theileria ovis (14.35%), T.
      lestoquardi (7.7%), T. uilenbergi (5.6%) and Babesia ovis (1.5%). T. uilenbergi
      is detected for the first time in Iraq. Coinfection of sheep with different
      pathogens could be observed in this study, and it was found that 45 of 195 (23%)
      of the samples contained more than one pathogen. Even triple-positive samples
      were identified in 3% of the investigated animals. In conclusion, we confirm the
      coinfection of sheep with various haemoparasitic pathogen species in the
      Kurdistan Region of Iraq. Further investigations are needed to reveal the
      epidemiology of the diseases, the respective tick vectors, and, in the case of
      coinfection, pathogens' interaction and possible cross-protection. 

PMID- 24589111
TI  - Development of a real-time PCR assay for detection and quantification of
      Anaplasma ovis infection.
AB  - Anaplasma ovis is a tick-borne intra-erythrocytic rickettsial pathogen of small
      ruminants. Real-time PCR possesses merits of rapidity, accuracy, reliability,
      automation and ease of standardization, but has not been used for detection of A.
      ovis, to the best of our knowledge. In this study, a real-time PCR assay was
      developed for detection and quantification of A. ovis. Species-specific primers
      and TaqMan probe were designed based on the gltA gene. No cross-reactions were
      observed with Anaplasma marginale, Anaplasma bovis, Anaplasma phagocytophilum,
      Borrelia burgdorferi s. l., Chlamydia psittaci, Mycoplasma mycoides, Theileria
      luwenshuni and Babesia sp. Xinjiang isolate. Analytic sensitivity results
      revealed that real-time PCR could detect as few as 10 copies of the gltA gene.
      The performance of real-time PCR was assessed by testing 254 blood samples from
      goats and comparing with the results from conventional PCR. This demonstrated
      that the real-time PCR assay was significantly more sensitive than conventional
      PCR. Our results indicated that real-time PCR is a useful approach for detecting
      A. ovis infections and has potential as an alternative tool for ecological and
      epidemiological surveillance of ovine anaplasmosis. 

PMID- 24589112
TI  - A Molecular survey of Anaplasma spp., Rickettsia spp., Ehrlichia canis and
      Babesia microti in foxes and fleas from Sicily.
AB  - Fleas (Insecta: Siphonaptera) are obligate bloodsucking insects, which parasitize
      birds and mammals, and are distributed throughout the world. Several species have
      been implicated in pathogen transmission. This study aimed to monitor red foxes
      and the fleas isolated from them in the Palermo and Ragusa provinces of Sicily,
      Italy, as these organisms are potential reservoirs and vectors of pathogens.
      Thirteen foxes (Vulpes vulpes) and 110 fleas were analysed by polymerase chain
      reaction (PCR) to detect DNA of the pathogens Ehrlichia canis, Babesia microti,
      Rickettsia spp., Anaplasma phagocytophilum, Anaplasma platys, Anaplasma marginale
      and Anaplasma ovis. In the foxes, A. ovis was detected in only one animal,
      whereas the prevalence of the E. canis pathogen was 31%. B. microti and
      Rickettsia spp. were not detected. Of all of the collected fleas, 75 belonged to
      the species Xenopsylla cheopis, 32 belonged to Ctenocephalides canis, two
      belonged to Ctenocephalides felis and one belonged to Cediopsylla inaequalis. In
      the fleas, the following pathogens were found: A. ovis (prevalence 25%), A.
      marginale (1%), A. phagocytophilum (1%), Rickettsia felis (2%) and E. canis (3%).
      X. cheopis was the flea species most frequently infected with Anaplasma, in
      particular A. ovis (33%), A. marginale (1%) and A. phagocytophilum (1%). Both C.
      felis exemplars were positive for R. felis. E. canis was found in the lone C.
      inaequalis and also in 3% of the X. cheopis specimens. No fleas were positive for
      B. microti or A. platys. As foxes often live in proximity to domestic areas, they
      may constitute potential reservoirs for human and animal parasites. Further
      studies should be performed on fleas to determine their vectorial capacity.

PMID- 24589113
TI  - Evidence for extensive genetic diversity and substructuring of the Babesia bovis
      metapopulation.
AB  - Babesia bovis is a tick-transmitted haemoprotozoan and a causative agent of
      bovine babesiosis, a cattle disease that causes significant economic loss in
      tropical and subtropical regions. A panel of nineteen micro- and minisatellite
      markers was used to estimate population genetic parameters of eighteen parasite
      isolates originating from different continents, countries and geographic regions
      including North America (Mexico, USA), South America (Argentina, Brazil), the
      Middle East (Israel) and Australia. For eleven of the eighteen isolates, a unique
      haplotype was inferred suggesting selection of a single genotype by either in
      vitro cultivation or amplification in splenectomized calves. Furthermore, a high
      genetic diversity (H = 0.780) over all marker loci was estimated. Linkage
      disequilibrium was observed in the total study group but also in sample subgroups
      from the Americas, Brazil, and Israel and Australia. In contrast, corresponding
      to their more confined geographic origin, samples from Israel and Argentina were
      each found to be in equilibrium suggestive of random mating and frequent genetic
      exchange. The genetic differentiation (F(ST)) of the total study group over all
      nineteen loci was estimated by analysis of variance (Theta) and Nei's estimation
      of heterozygosity (G(ST')) as 0.296 and 0.312, respectively. Thus, about 30% of
      the genetic diversity of the parasite population is associated with genetic
      differences between parasite isolates sampled from the different geographic
      regions. The pairwise similarity of multilocus genotypes (MLGs) was assessed and
      a neighbour-joining dendrogram generated. MLGs were found to cluster according to
      the country/continent of origin of isolates, but did not distinguish the
      attenuated from the pathogenic parasite state. The distant geographic origin of
      the isolates studied allows an initial glimpse into the large extent of genetic
      diversity and differentiation of the B. bovis population on a global scale.

PMID- 24589114
TI  - Identification and characterization of Theileria annulata heat-shock protein 90
      (HSP90) isoforms.
AB  - Heat-shock proteins (HSPs) refer to a group of proteins whose synthesis is
      enhanced upon sudden increase in temperature or exposure to a variety of other
      stressors. In this study, Theileria annulata (T. annulata) HSP90 was identified
      and characterized as a first step to understand the function of this molecule in
      T. annulata-infected cells. Our results indicated the existence in the genome of
      T. annulata of two HSP90 genes: one located in chromosome one (TaHSP90-Chr1) and
      the other in chromosome four (TaHSP90-Chr4). The amino acid alignment between the
      two isoforms has shown identity and similarity values of 23.52% and 30.26%,
      respectively. Theileria annulata recombinant HSP90 proteins were expressed using
      a bacterial expression system and could be recognized in Western blots by rabbit
      anti-serum raised against an antigenic peptide derived from a unique sequence of
      TaHSP90-Chr1. On the other hand, bovine HSP90 was detected in T. annulata
      infected cells using Western blot and immunocytostaining. To demonstrate the
      effect of the inhibition of HSP90 on the survival of T. annulata-infected cells,
      Geldanamycin (GA), a specific inhibitor for HSP90, was used. Upon GA treatment,
      p53 was observed to translocate into the host cell nucleus, a phenomenon that
      occurs in cells undergoing apoptosis. Using flowcytometry, a significant increase
      (P = 0.028) in cell death (%) was observed in T. annulata-infected cells treated
      with two different GA concentrations, 0.5 and 1 MUm, and incubated for 24, 48 and
      72 h.

PMID- 24589115
TI  - Comparing terpenes from plant essential oils as pesticides for the poultry red
      mite (Dermanyssus gallinae).
AB  - Resistance to conventional synthetic pesticides has been widely reported in
      ticks, parasitic mites and other pests of veterinary and medical significance.
      New and novel approaches to manage these pests are therefore needed to ensure
      efficient control programmes that can be implemented now and in the future.
      Recent research in this area has focused on the pesticidal potential of plant
      essential oils. These products are attractive as pesticide candidates on the
      grounds of low mammalian toxicity, short environmental persistence and complex
      chemistries (limiting the development of pest resistance against them). Although
      issues may exist concerning reliability in efficacy of essential oils, these may
      be overcome by identifying and developing bioactive oil components for use in
      pest management. In the current work, three such components (terpenes) found in
      essential oils (eugenol, geraniol and citral) were tested against the poultry red
      mite Dermanyssus gallinae. All provided 100% mortality in toxicity tests when
      undiluted. Even at 1% of this dose, eugenol was 20% effective against
      experimental pest populations, although the remaining terpenes were largely
      ineffective at this concentration. 

PMID- 24589116
TI  - Mosquito surveillance in northwestern Italy to monitor the occurrence of tropical
      vector-borne diseases.
AB  - Mosquito-borne arboviruses (MBV) represent an important health problem, causing
      diseases and deaths both in human and animals mainly in tropical and subtropical
      countries. In recent years, they have emerged also in temperate regions where
      they have caused epidemics. Of mounting concern among public health authorities
      in Europe are zoonotic mosquito-borne viruses belonging to the Flavivirus genus.
      The aim of this study was to carry out active surveillance on mosquitoes in two
      regions of northwestern Italy (Liguria and Piedmont) to gain a better knowledge
      of the mosquito populations by identifying potential vectors of arboviruses and
      to investigate arbovirus infection. A network of 61 CO2 CDC traps was placed in
      the study area; sampling was conducted from May to October 2011. A total of
      46,677 mosquitoes was collected, identified to species level, and classified
      according to their vector competence. Mosquitoes collected from 16 traps,
      selected according to risk-based factors, were tested by biomolecular analysis to
      detect flavivirus infection. This study highlights the importance of
      entomological surveillance in northwestern Italy because most of the mosquitoes
      collected were found to have high vector competence. Moreover, the risk-based
      virological surveillance allowed to detect the presence of mosquito flavivirus
      RNA, phylogenetically closely related to the MMV Spanish isolate, in three pools
      and USUV RNA in one pool in new areas where it has not been reported previously.
      The availability of continuous data on mosquito populations provides invaluable
      information for use in cases of an epidemic emergency. Maintenance of this
      integrated system for the next years will provide stronger data that can inform
      the design of a risk-based surveillance for the early detection of the occurrence
      of outbreaks of tropical MBDs.

PMID- 24589117
TI  - Whole antigenic lysates of Ixodes ricinus, but not Der-p2 allergen-like protein,
      are potent inducers of basophil activation in previously tick-exposed human
      hosts.
AB  - The clinical suspicion of tick anaphylaxis is based on a history of the bite and
      occurs often during the warm season. Further arguments are the presence of
      natural hosts in the immediate environment and, eventually, the identification of
      the tick. The diagnosis is confirmed when immediate-type sensitization is shown
      by positive skin prick tests performed with specific tick extracts or the
      demonstration of specific IgE in vitro. In the current study, we hypothesize that
      hard tick-derived material contains potent inducers being able to promote
      basophil stimulation, which correlates with a sensitization immunological
      response following tick bites. To this end, biological material from two hard
      tick cell lines (IRE11 and IDE8 - derived from Ixodes ricinus and I. scapularis,
      respectively) as well as I. ricinus salivary gland and body lysates were used in
      a human basophil activation test (BAT) to analyse binding and cross-linking
      capacity of membrane-bound IgE, because basophils are one of the main effector
      cells of allergic reactions. Additionally, Der-p2 allergen-like gene from I.
      ricinus was recombinantly expressed as a 15-kDa histidine-tagged fusion protein,
      purified and included as a stimulus within the setup. Blood was drawn and
      submitted to BAT screening from a pool of 36 individuals, both bitten and who
      served solely as negative controls. We have found that seven subjects (19%), all
      of whom were at least two times tick-bitten, positively reacted to the
      aforementioned stimuli, whereas the reactivity level of the ones bearing single
      bites proved to be within the normal range. Moreover, no significant upregulation
      of the assessed basophil activation marker was detected in the case of Der-p2,
      except a faint reaction at high dosages. We conclude that at least two tick bites
      of the human host must occur in order to induce significant basophil activation. 

PMID- 24589118
TI  - Subolesin/Akirin vaccines for the control of arthropod vectors and vectorborne
      pathogens.
AB  - Diseases transmitted by arthropod vectors such as mosquitoes, ticks and sand
      flies greatly impact human and animal health, and therefore, their control is
      important for the eradication of vectorborne diseases (VBD). Vaccination is an
      environmentally friendly alternative for vector control that allows control of
      several VBD by targeting their common vector. Recent results have suggested that
      subolesin (SUB) and its orthologue in insects, akirin (AKR) are good candidate
      antigens for the control of arthropod vector infestations and pathogen infection.
      SUB was discovered as a tick-protective antigen in Ixodes scapularis. Vaccination
      trials with recombinant SUB/AKR demonstrated effective control of arthropod
      vector infestations in various hard and soft tick species, mosquitoes, sand
      flies, poultry red mites and sea lice by reducing their numbers, weight,
      oviposition, fertility and/or moulting. SUB/AKR vaccination also reduced tick
      infection with tickborne pathogens, Anaplasma phagocytophilum, A. marginale,
      Babesia bigemina and Borrelia burgdorferi. The effect of vaccination on different
      hosts, vector species, developmental stages and vectorborne pathogen infections
      demonstrated the feasibility of SUB/AKR universal vaccines for the control of
      multiple vector infestations and for reduction in VBD. 

PMID- 24589119
TI  - Parents' experiences and expectations of care in pregnancy after stillbirth or
      neonatal death: a metasynthesis.
AB  - BACKGROUND: Pregnancy after perinatal death is characterised by elevated stress
      and anxiety, increasing the risk of adverse short-term and long-term outcomes.
      OBJECTIVES: This metasynthesis aimed to improve understanding of parents'
      experiences of maternity care in pregnancy after stillbirth or neonatal death.
      SEARCH STRATEGY: Six electronic databases were searched using predefined search
      terms. SELECTION CRITERIA: English language studies using qualitative methods to
      explore the experiences of parents in pregnancy after perinatal loss, were
      included subject to quality appraisal framework. DATA COLLECTION AND ANALYSIS:
      Searches were initiated in December 2011 and finalised in March 2013. Studies
      were synthesised using an interpretive approach derived from meta-ethnography.
      MAIN RESULTS: Fourteen studies were included in the synthesis, graded A (no or
      few flaws, high trustworthiness; n = 5), B (some flaws, unlikely to affect
      trustworthiness; n = 5) and C (some flaws, possible impact on trustworthiness; n
      = 4). Three main themes were identified; co-existence of emotions, helpful and
      unhelpful coping activities and seeking reasssurance through interactions.
      CONCLUSION: Parents' experiences of pregnancy are profoundly altered by previous
      perinatal death; conflicted emotions, extreme anxiety, isolation and a lack of
      trust in a good outcome are commonly reported. Emotional and psychological
      support improves parents' experiences of subsequent pregnancy, but the absence of
      an evidence base may limit consistent delivery of optimal care within current
      services.

PMID- 24589120
TI  - Role of toll-like receptor 2 in ischemic demyelination and oligodendrocyte death.
AB  - White matter is frequently involved in ischemic stroke, and progressive ischemic
      white matter injuries are associated with various neurologic dysfunctions in the
      elderly population. Demyelination and oligodendrocyte (OL) loss are prominent
      features of ischemic white matter injury. Endothelin-1 injection into the
      internal capsule resulted in a localized demyelinating lesion in mice, where loss
      of OL lineage cells and inflammatory cell infiltration were observed accompanied
      by upregulation of toll-like receptor 2 (TLR2). Intriguingly, the extent of
      demyelinating pathology was markedly larger in TLR2 deficient mice than that of
      wild-type (WT) mice. TLR2 deficient mice showed enhanced OL death and decreased
      phosphorylation of ERK1/2 compared with WT animals. Cultured OLs from TLR2
      deficient mice were more vulnerable to oxygen-glucose deprivation than WT OLs.
      Applying TLR2 agonists Pam3CSK4 or Zymosan after oxygen-glucose deprivation
      substantially rescued WT OL death with augmentation of ERK1/2 phosphorylation.
      Treatment with Pam3CSK4 also reduced the extent of endothelin-1 induced ischemic
      demyelination in vivo. Our data indicate TLR2 may provide endogenous protective
      effects on ischemic demyelination and OL degeneration.

PMID- 24589121
TI  - Compound complex curves: the authentic geometry of esthetic dentistry.
AB  - Observers are drawn to the intricate and unpredictable way light reflects off the
      compound complex curved surfaces seen in nature, art, and industry. Teeth are no
      exception, containing as they do such detail in their gross anatomy, fine
      anatomic detail, and surface texture. Compound complex curves are particularly
      important when engineered materials are used to mimic naturally occurring
      objects, including prosthetic teeth, and they can provide both authenticity and
      beauty. The purpose of this article was to describe the nature of compound
      complex curves, their historical context, and their importance in creating
      natural-looking prostheses. Classically, such curves have been described by using
      descriptive qualitative methods or quantitative mathematical methods; now these
      approaches merge. Natural tooth anatomy contains interlinked features at
      different levels of scale from gross to fine surface texture detail. These curves
      should be created appropriately for individual restorative treatments. 

PMID- 24589122
TI  - A critical appraisal of evidence-based dentistry: the best available evidence.
AB  - STATEMENT OF PROBLEM: The principle of evidence-based dentistry requires that
      relevant scientific literature be integrated into the dentist's practice and the
      patient's treatment needs and wishes. This approach involves critically
      appraising the scientific literature for the best available evidence in order to
      make clinical decisions. PURPOSE: The purpose of the study was to critically
      appraise the process by which a practitioner attempts to make an evidenced-based
      clinical decision. This process is illustrated by evaluating the clinical
      literature pertaining to zirconia-based single crowns. MATERIAL AND METHODS: An
      electronic search was performed in PubMed and the Cochrane Library by using
      Boolean operators for articles published in English between January 1950 and
      October 2012 to address the PICO (patients, intervention, comparison, outcome)
      question, "In adults, how does the long term prognosis of zirconia-based single
      crowns compare to conventional single crowns on natural teeth?" Comparisons were
      made across the publications to determine the quality of relevant information.
      RESULTS: Three systematic reviews included 4 clinical trials. Two randomized
      clinical trials and 1 retrospective study met the search criteria but were not
      identified in the systematic reviews. The definitions of the outcomes and the
      presentation of the data varied among studies. CONCLUSIONS: The lack of
      standardization of reporting data, the nonstandardized definitions of outcomes,
      and the impact of the length of the research study were identified as problems
      that need to be addressed to improve the quality of systematic reviews and other
      clinical trials.

PMID- 24589123
TI  - The Effects of Computerized Cognitive Control Training on Community Adults with
      Depressed Mood.
AB  - BACKGROUND: Depression is frequently characterized by patterns of inflexible,
      maladaptive, and ruminative thinking styles, which are thought to result from a
      combination of decreased attentional control, decreased executive functioning,
      and increased negative affect. Cognitive Control Training (CCT) uses computer
      based behavioral exercises with the aim of strengthening cognitive and emotional
      functions. A previous study found that severely depressed participants who
      received CCT exhibited reduced negative affect and rumination as well as improved
      concentration. AIMS: The present study aimed to extend this line of research by
      employing a more stringent control group and testing the efficacy of three
      sessions of CCT over a 2-week period in a community population with depressed
      mood. METHOD: Forty-eight participants with high Beck Depression Inventory (BDI
      II) scores were randomized to CCT or a comparison condition (Peripheral Vision
      Training; PVT). RESULTS: Significant large effect sizes favoring CCT over PVT
      were found on the BDI-II (d = 0.73, p < .05) indicating CCT was effective in
      reducing negative mood. Additionally, correlations showed significant
      relationships between CCT performance (indicating ability to focus attention on
      CCT) and state affect ratings. CONCLUSIONS: Our results suggest that CCT is
      effective in altering depressed mood, although it may be specific to select mood
      dimensions.

PMID- 24589125
TI  - In-line monitoring of particle size in a fluid bed granulator: investigations
      concerning positioning and configuration of the sensor.
AB  - According to the ICH Q8 guideline, analytic technologies (PAT) are important
      tools for characterization and optimization of pharmaceutical manufacturing
      processes. Particle size as a critical quality attribute for granules is
      therefore an important parameter that should be monitored during the fluid bed
      granulation process. This work focusses on optimizing position and configuration
      of an SFT-sensor for the in-line measurement of particle size distribution in a
      Glatt GPCG 3 fluid bed granulator. As model-substances, different grades of
      microcrystalline cellulose were used. The in-line measured particle size and
      particle rate in the sensor were evaluated. A sensor position in the deceleration
      zone of the granulator was found to be promising for in-line particle size
      measurement. Most reliable data were generated in this position when the probe
      was placed in a distance of 11cm from the chamber wall to avoid bias by the inlet
      air stream. No major influence of rotation angle of the probe was found in this
      position. Furthermore, an entire fluid bed granulation process was successfully
      monitored with the sensor installed in the optimized setting.

PMID- 24589124
TI  - Nifedipine versus atosiban in the treatment of threatened preterm labour
      (Assessment of Perinatal Outcome after Specific Tocolysis in Early Labour:
      APOSTEL III-Trial).
AB  - BACKGROUND: Preterm birth is the most common cause of neonatal morbidity and
      mortality. Postponing delivery for 48 hours with tocolytics to allow for maternal
      steroid administration and antenatal transportation to a centre with neonatal
      intensive care unit facilities is the standard treatment for women with
      threatening preterm delivery in most centres. However, there is controversy as to
      which tocolytic agent is the drug of first choice. Previous trials have focused
      on tocolytic efficacy and side effects, and are probably underpowered to detect
      clinically meaningfull differences in neonatal outcome. Thus, the current
      evidence is inconclusive to support a balanced recommendation for clinical
      practice. This multicenter randomised clinical trial aims to compare nifedipine
      and atosiban in terms of neonatal outcome, duration of pregnancy and maternal
      side effects. METHODS/DESIGN: The Apostel III trial is a nationwide multicenter
      randomised controlled study. Women with threatened preterm labour (gestational
      age 25 - 34 weeks) defined as at least 3 contractions per 30 minutes, and 1) a
      cervical length of <= 10 mm or 2) a cervical length of 11-30 mm and a positive
      Fibronectin test or 3) ruptured membranes will be randomly allocated to treatment
      with nifedipine or atosiban. Primary outcome is a composite measure of severe
      neonatal morbidity and mortality. Secondary outcomes will be time to delivery,
      gestational age at delivery, days on ventilation support, neonatal intensive care
      (NICU) admittance, length admission in neonatal intensive care, total days in
      hospital until 3 months corrected age, convulsions, apnoea, asphyxia, proven
      meningitis, pneumothorax, maternal side effects and costs. Furthermore, an
      economic evaluation of the treatment will be performed. Analysis will be by
      intention to treat principle. The power calculation is based on an expected 10%
      difference in the prevalence of adverse neonatal outcome. This implies that 500
      women have to be randomised (two sided test, beta 0.2 at alpha 0.05). DISCUSSION:
      This trial will provide evidence on the optimal drug of choice in acute tocolysis
      in threatening preterm labour. TRIAL REGISTRATION:  CLINICAL TRIAL REGISTRATION:
      NTR2947, date of registration: June 20th 2011.

PMID- 24589126
TI  - Patterns of tertiary prophylaxis in Canadian adults with severe and moderately
      severe haemophilia B.
AB  - From a young age patients with severe and moderately severe FIX deficiency
      (haemophilia B) can experience spontaneous or traumatic bleeding and joint
      destruction may result. The use of coagulation factor IX concentrate to prevent
      anticipated bleeding, as primary or secondary prophylaxis, has become a common
      and recommended practice in children. The current practice of using tertiary
      prophylaxis, in the presence of established joint arthropathy, in adults with
      haemophilia B is not well characterized. This observational study was conducted
      to gain a better understanding of the recent Canadian experience with tertiary
      prophylaxis in adults with severe and moderately severe haemophilia B. Data were
      collected from all eligible adult (>= 18 years of age) males with baseline FIX:C
      <= 2% from seven Canadian Hemophilia Treatment centres over a 2-year observation
      period from 2009 to 2011. Thirty-four per cent of the 67 subjects with moderately
      severe haemophilia B were exposed to prophylaxis with the majority as continuous
      prophylaxis (>=45 weeks year(-1) ). The severe subgroup (FIX:C < 1%) demonstrated
      a 52% exposure rate. None had primary prophylaxis exposure in childhood. Eighty
      one per cent used once or twice weekly infusion regimens and reported a median
      annual bleeding rate of five bleeds per year versus four bleeds per year for
      those using on-demand treatment. Annual median factor utilization for all
      subjects using prophylaxis was 196,283 U year(-1) compared to 46,361 U year(-1)
      for on demand. Approximately 50% of adults with severe haemophilia B are using
      continuous tertiary prophylaxis in Canada, a practice likely to increase which
      warrants further study.

PMID- 24589127
TI  - The effect of addition of liraglutide to high-dose intensive insulin therapy: a
      randomized prospective trial.
AB  - AIMS: Patients with type 2 diabetes and insulin resistance may require high
      insulin doses to control hyperglycaemia. The addition of glucagon-like peptide-1
      receptor agonists (GLP-1 RAs) to basal insulin therapy has been shown to reduce
      insulin requirement while reducing insulin-associated weight gain [1,2]. The
      effect of GLP-1 RA therapy added to intensive (basal/bolus) insulin therapy has
      not been studied in a prospective trial. This trial evaluated the effect of the
      addition of liraglutide to high-dose intensive insulin therapy compared with
      standard insulin up-titration in obese insulin-resistant patients with type 2
      diabetes requiring high-dose insulin therapy. METHODS: Thirty-seven subjects with
      type 2 diabetes requiring >100 units of insulin daily administered either by
      continuous subcutaneous insulin infusion (CSII) or by multiple daily injections
      (MDIs) with or without metformin were randomized to receive either liraglutide
      plus insulin (LIRA) or intensive insulin only (controls). Liraglutide was
      initiated at 0.6 mg subcutaneously (sq) per day and increased to either 1.2 or
      1.8 mg daily in combination with intensive insulin therapy. Controls received
      intensive insulin up-titration only. RESULTS: At 6 months, subjects receiving
      liraglutide plus insulin experienced statistically significant reductions in
      HbA1c, weight, insulin dose and glycaemic variability (GV) by continuous glucose
      monitor (CGM) compared with the control group receiving insulin only.
      CONCLUSIONS: Adding liraglutide to intensive high-dose (basal/bolus) insulin
      therapy results in greater improvement in glycaemic control than insulin therapy
      alone, with additional benefits of weight loss and reduced GV.

PMID- 24589128
TI  - Opioid conversion ratios used in palliative care: is there an Australian
      consensus?
AB  - BACKGROUND: Opioid switching or rotation is reported to be a common practice in
      palliative care. Published tables of opioid conversion ratios have been found to
      vary in their recommendations, potentially leading to significant differences in
      clinical practice. AIMS: To identify common practices in the calculation of
      opioid equianalgesia by specialist palliative medicine practitioners and
      trainees. METHOD: An anonymous, cross-sectional, online survey completed by 85
      Australian palliative care specialists or advanced trainees. Questions focused on
      conversion ratios used in switching between oral and parenteral opioid doses;
      conversion ratios used when switching from other opioids to oral morphine; and
      practice of commencing methadone. RESULTS: The majority of respondents calculated
      equianalgesic doses for morphine, oxycodone and hydromorphone using the same
      conversion ratios. Methadone was used almost equally as either the sole opioid or
      as a 'co-opioid'. The majority surveyed converted slow-release hydromorphone
      differently to the manufacturer's recommendations. CONCLUSION: Further discussion
      among Australian palliative care specialist organisations is recommended in order
      to produce uniform conversion guidelines to improve consistency and safety in the
      prescribing of opioids.

PMID- 24589129
TI  - Maternal obesity and excess of fetal growth in pre-eclampsia.
AB  - OBJECTIVE: To assess whether the reported excess of large for gestational age
      (LGA) neonates in pre-eclamptic women delivering at term is attributable to
      maternal obesity. DESIGN, SETTING AND POPULATION: Population-based observational
      study including 77,294 singleton pregnancies registered in the Medical Birth
      Registry of Norway between 2007 and 2010. METHODS: Comparison of birthweight
      percentiles and z-scores between women with and without pre-eclampsia. MAIN
      OUTCOME MEASURES: Odds ratio (OR) of LGA and z-scores of birthweight in relation
      to pre-eclampsia. RESULTS: Pre-eclamptic women delivering at term had increased
      risk of having LGA neonates. Unadjusted ORs with 95% confidence interval (95% CI)
      of LGA above the 90th and 95th birthweight centiles were 1.4, 95% CI 1.2-1.6 and
      1.6, 95% CI 1.3-1.9, respectively. The excess of LGA persisted after including
      gestational diabetes and diabetes types 1 and 2 in a multivariate analysis
      (corresponding ORs 1.3, 95% CI 1.1-1.5 and 1.4, 95% CI 1.2-1.7), but disappeared
      after adjusting for maternal prepregnant body mass index (ORs 1.1, 95% CI 0.9-1.2
      and 1.1, 95% CI 0.9-1.3). CONCLUSIONS: This study suggests accelerated fetal
      growth in a subset of pre-eclamptic women delivering at term. The excess of LGA
      neonates is attributable to maternal obesity among pre-eclamptic women delivering
      at term. The maternal obesity epidemic may lead to an increased prevalence of
      both pre-eclampsia and LGA neonates among women delivering at term.

PMID- 24589130
TI  - Empathy in high-tech and high-touch medicine.
AB  - OBJECTIVE: Surgeons and psychiatrists have been described as two contrary groups,
      the one healing by hands and the other by words. Empathy is needed in every
      physician-patient relationship. We tested whether (1) surgeons and psychiatrists
      show different levels of cognitive and emotional empathy; (2) measurements of
      cognitive and emotional empathy correlate with physician-specific empathy; and
      (3) gender, experience, and career choices are influencing factors. METHODS: 56
      surgeons and 50 psychiatrists participated. We measured empathy with the
      Jefferson Scale of Physician Empathy (JSPE), cognitive empathy with the Reading
      the Mind in the Eyes Test Revised (RME-R6), and emotional empathy with the
      Balanced Emotional Empathy Scale (BEES). RESULTS: Male psychiatrists scored
      significantly higher than that of male surgeons (118.0+/-9.86 vs. 107.5+/-13.84;
      p=0.0006) in the JSPE. Analytically trained psychiatrists scored significantly
      higher in the JSPE than that of behaviorally trained psychiatrists (p=0.024, F
      test, adjusted for gender). Both the RME and the BEES correlated positively with
      the JSPE. CONCLUSION: Higher scores for empathy were found in male psychiatrists
      than in male surgeons. PRACTICE IMPLICATIONS: Further research is needed to learn
      about the effects of general medical training on empathy.

PMID- 24589132
TI  - The DRY motif at work: the P2Y12 receptor case.

PMID- 24589133
TI  - Promoting medical competencies through international exchange programs: benefits
      on communication and effective doctor-patient relationships.
AB  - BACKGROUND: Universities are increasingly organizing international exchange
      programs to meet the requirements of growing globalisation in the field of health
      care. Analyses based on the programs' fundamental theoretical background are
      needed to confirm the learning value for participants. This study investigated
      the extent of sociocultural learning in an exchange program and how sociocultural
      learning affects the acquisition of domain-specific competencies. METHODS:
      Sociocultural learning theories were applied to study the learning effect for
      German medical students from the LMU Munich, Munich, Germany, of participation in
      the medical exchange program with Jimma University, Jimma, Ethiopia. First, we
      performed a qualitative study consisting of interviews with five of the first
      program participants. The results were used to develop a questionnaire for the
      subsequent, quantitative study, in which 29 program participants and 23 matched
      controls performed self-assessments of competencies as defined in the Tuning
      Project for Health Professionals. The two interrelated studies were combined to
      answer three different research questions. RESULTS: The participants rated their
      competence significantly higher than the control group in the fields of doctor
      patient relationships and communication in a medical context. Participant
      responses in the two interrelated studies supported the link between the findings
      and the suggested theoretical background. CONCLUSION: Overall, we found that the
      exchange program affected the areas of doctor-patient relationships and effective
      communication in a medical context. Vygotsky's sociocultural learning theory
      contributed to explaining the learning mechanisms of the exchange program.

PMID- 24589134
TI  - RhHB1 mediates the antagonism of gibberellins to ABA and ethylene during rose
      (Rosa hybrida) petal senescence.
AB  - Rose (Rosa hybrida) is one of the most important ornamental plants worldwide;
      however, senescence of its petals terminates the ornamental value of the flower,
      resulting in major economic loss. It is known that the hormones abscisic acid
      (ABA) and ethylene promote petal senescence, while gibberellins (GAs) delay the
      process. However, the molecular mechanisms underlying the antagonistic effects
      amongst plant hormones during petal senescence are still unclear. Here we
      isolated RhHB1, a homeodomain-leucine zipper I transcription factor gene, from
      rose flowers. Quantitative RT-PCR and GUS reporter analyses showed that RhHB1 was
      strongly expressed in senescing petals, and its expression was induced by ABA or
      ethylene in petals. ABA or ethylene treatment clearly accelerated rose petal
      senescence, while application of the gibberellin GA3 delayed the process.
      However, silencing of RhHB1 delayed the ABA- or ethylene-mediated senescence, and
      resulted in higher petal anthocyanin levels and lower expression of RhSAG12.
      Moreover, treatment with paclobutrazol, an inhibitor of GA biosynthesis,
      repressed these delays. In addition, silencing of RhHB1 blocked the ABA- or
      ethylene-induced reduction in expression of the GA20 oxidase encoded by
      RhGA20ox1, a gene in the GA biosynthetic pathway. Furthermore, RhHB1 directly
      binds to the RhGA20ox1 promoter, and silencing of RhGA20ox1 promoted petal
      senescence. Eight senescence-related genes showed substantial differences in
      expression in petals after treatment with GA3 or paclobutrazol. These results
      suggest that RhHB1 mediates the antagonistic effect of GAs on ABA and ethylene
      during rose petal senescence, and that the promotion of petal senescence by ABA
      or ethylene operates through an RhHB1-RhGA20ox1 regulatory checkpoint. 

PMID- 24589135
TI  - Assessing vascular status and risk of latent ischemia with ankle fracture: a case
      report and algorithm for treatment.
AB  - A paucity of published studies and clinical recommendations are available
      regarding ankle fracture and its association with vascular injury, likely because
      of the lower incidence relative to the more commonly seen popliteal artery injury
      after knee dislocation. In the present case report, we describe a previously
      healthy patient who experienced a pilon type ankle fracture (AO 43C2) with
      fibular and syndesmotic involvement, followed by a subacute presentation of
      vascular ischemia weeks after the initial injury and repair, ultimately leading
      to a major amputation. The failure to identify an occult, vascular injury can
      have devastating consequences. Guidelines regarding the identification and
      management of displaced ankle fracture-associated vascular injury, drawing
      evidence from other traumatic injury complexes, could improve the clinical
      outcomes. We aim to raise awareness of the association of vascular embarrassment
      secondary to ankle fracture by proposing a clinical practice algorithm to aid
      clinicians in recognizing traumatic vascular injury at the earliest and most
      treatable stage. 

PMID- 24589136
TI  - Retrospective analysis of the rate and interval to union for joint arthrodesis of
      the foot and ankle.
AB  - Arthrodesis is a common procedure indicated for surgical treatment of end-stage
      degenerative joint disease of the foot and ankle. Many published studies have
      reviewed the union rate, focusing on specific technique or fixation. However,
      studies reporting on the average period required to achieve fusion, irrespective
      of the type of fixation or surgical method used, have been lacking. We report on
      the union rate and interval to fusion in patients who had undergone primary
      arthrodesis of various joints of the foot and ankle. A retrospective review of
      the medical records of 135 patients was performed. The specific joints studied
      were ankle, and the subtalar, triple, first tarsometatarsal, first
      metatarsophalangeal, and hallux interphalangeal joints. Our results showed that
      the average interval for complete fusion was significantly less for the joints in
      the forefoot, with the subtalar joint, ankle, and triple arthrodesis requiring a
      longer period to achieve complete fusion. The nonunion rate was also greater when
      the fusion involved the joints of the rearfoot. Our results have refuted the idea
      that 6 weeks is the minimum period required to achieve fusion in the foot and
      ankle. The results of our study support the need for additional education of the
      patients and surgeons that the interval required for recovery after foot and
      ankle fusion depends on the location and surface area that has been fused. 

PMID- 24589137
TI  - Early results of first metatarsophalangeal joint replacement using the ToeFit
      PlusTM prosthesis.
AB  - The aim of the present study was to investigate the outcomes of first
      metatarsophalangeal replacement for hallux rigidus using the Smith & Nephew
      ToeFit-PlusTM implant. We assessed the outcomes of 69 first metatarsophalangeal
      joint replacements using the American Orthopaedic Foot and Ankle Society score
      preoperatively and annually postoperatively, with retrospective radiologic
      review. All operations were performed by the same surgeon within 2 centers. A
      total of 69 arthroplasties were performed within the study period (57 patients).
      The median American Orthopaedic Foot and Ankle Society score at 1 year was 100
      (interquartile range 100 to 100), at 2 years was 100 (interquartile range 95 to
      100), at 3 years was 100 (interquartile range 87.5 to 100), and at 4 years, it
      was 100 (interquartile range 91.25 to 100). Radiolucencies around the phalangeal
      component were seen in 23 cases; however, this was symptomatic in only 2
      patients, who required revision surgery. Our early results have shown that first
      metatarsophalangeal joint replacement surgery with the ToeFit-PlusTM prosthesis
      results in significant improvements in the American Orthopaedic Foot and Ankle
      Society scores for most patients; however, longer term follow-up is required to
      monitor the clinical effect of radiolucency around the phalangeal component. 

PMID- 24589138
TI  - Ethylene-forming enzyme and bioethylene production.
AB  - Worldwide, ethylene is the most produced organic compound. It serves as a
      building block for a wide variety of plastics, textiles, and chemicals, and a
      process has been developed for its conversion into liquid transportation fuels.
      Currently, commercial ethylene production involves steam cracking of fossil
      fuels, and is the highest CO2-emitting process in the chemical industry.
      Therefore, there is great interest in developing technology for ethylene
      production from renewable resources including CO2 and biomass. Ethylene is
      produced naturally by plants and some microbes that live with plants. One of the
      metabolic pathways used by microbes is via an ethylene-forming enzyme (EFE),
      which uses alpha-ketoglutarate and arginine as substrates. EFE is a promising
      biotechnology target because the expression of a single gene is sufficient for
      ethylene production in the absence of toxic intermediates. Here we present the
      first comprehensive review and analysis of EFE, including its discovery, sequence
      diversity, reaction mechanism, predicted involvement in diverse metabolic modes,
      heterologous expression, and requirements for harvesting of bioethylene. A number
      of knowledge gaps and factors that limit ethylene productivity are identified, as
      well as strategies that could guide future research directions. 

PMID- 24589140
TI  - Prevention, not cure.

PMID- 24589139
TI  - Factors associated with the use and quality of antenatal care in Nepal: a
      population-based study using the demographic and health survey data.
AB  - BACKGROUND: Good quality antenatal care (ANC) reduces maternal and neonatal
      mortality and improves health outcomes, particularly in low-income countries.
      Quality of ANC is measured by three dimensions: number of visits, timing of
      initiation of care and inclusion of all recommended components of care. Although
      some studies report on predictors of the first two indicators, no studies on the
      third indicator, which measures quality of ANC received, have been conducted in
      Nepal. Nepal follows the World Health Organization's recommendations of
      initiation of ANC within the first four months of pregnancy and at least four ANC
      visits during the course of an uncomplicated pregnancy. This study aimed to
      identify factors associated with 1) attendance at four or more ANC visits and 2)
      receipt of good quality ANC. METHODS: Data from Nepal Demographic and Health
      Survey 2011 were analysed for 4,079 mothers. Good quality ANC was defined as that
      which included all seven recommended components: blood pressure measurement;
      urine tests for detecting bacteriuria and proteinuria; blood tests for syphilis
      and anaemia; and provision of iron supplementation, intestinal parasite drugs,
      tetanus toxoid injections and health education. RESULTS: Half the women had four
      or more ANC visits and 85% had at least one visit. Health education, iron
      supplementation, blood pressure measurement and tetanus toxoid were the more
      commonly received components of ANC. Older age, higher parity, and higher levels
      of education and household economic status of the women were predictors of both
      attendance at four or more visits and receipt of good quality ANC. Women who did
      not smoke, had a say in decision-making, whose husbands had higher levels of
      education and were involved in occupations other than agriculture were more
      likely to attend four or more visits. Other predictors of women's receipt of good
      quality ANC were receiving their ANC from a skilled provider, in a hospital,
      living in an urban area and being exposed to general media. CONCLUSIONS:
      Continued efforts at improving access to quality ANC in Nepal are required. In
      the short term, less educated women from socioeconomically disadvantaged
      households require targeting. Long-term improvements require a focus on improving
      female education.

PMID- 24589141
TI  - Vaginal wet mount.

PMID- 24589143
TI  - Action and learning for safer healthcare systems.

PMID- 24589144
TI  - Equality, quality and human rights: a measured response?

PMID- 24589145
TI  - Systems and spread.
AB  - This is the fifth in a series of papers about the science of quality improvement.
      In this paper, we explore the issue of healthcare as a system and how this
      contributes to our understanding of how to spread improvement. 

PMID- 24589146
TI  - Patient perspectives on quality.
AB  - The patient perspective is central to quality improvement. This article describes
      how health services are involving individuals and the public in improving
      healthcare. It describes the importance and different methods of accessing
      patient and carer feedback on satisfaction, experience and outcomes, and explores
      current thinking on individual involvement, engagement in commissioning, and the
      role of the public in redesigning health services. 

PMID- 24589147
TI  - What is it about homeopathy that patients value? and what can family medicine
      learn from this?
AB  - BACKGROUND: Homeopathy is one of the most frequently used areas of complementary
      and alternative medicine (CAM). Previous research has focused in particular on
      the pharmacological effectiveness of homeopathy. There is intense discussion
      among German family medical practitioners as to whether family medicine should
      adopt elements of homeopathy because of the popularity of this treatment method.
      AIM: For the first time in Germany, patients with chronic conditions were asked
      about their views on the medical care provided by homeopathic medical
      practitioners. METHODS: The survey used questionnaire-based, semi-structured
      expert interviews, the contents of which were then analysed and summarised.
      RESULTS: A total of 21 women and five men aged from 29 to 75 years were surveyed.
      The 'fit' between therapist and patient proved to be particularly important. Both
      the initial homeopathic consultation and the process of searching for the
      appropriate medication were seen by patients as confidence-inspiring
      confirmations of the validity of homeopathic therapy which they considered
      desirable in this personalised form. CONCLUSION: The possible adoption by family
      medicine of elements of homeopathy may be seen as controversial, but this study
      again indicates the vital importance of successful communication to ensure a
      sustainable doctor-patient relationship. Advances in this sector not only require
      continuous efforts in the areas of medical training and professional development,
      but also touch on basic questions relating to the development of effective
      medical care, such as those currently being discussed in the context of the
      'patient-centred medical home'.

PMID- 24589148
TI  - Intervention fidelity in primary care complex intervention trials: qualitative
      study using telephone interviews of patients and practitioners.
AB  - BACKGROUND: Treatment fidelity has previously been defined as the degree to which
      a treatment or intervention is delivered to participants as intended.
      Underreporting of fidelity in primary care randomised controlled trials (RCTs) of
      complex interventions reduces our confidence that findings are due to the
      treatment or intervention being investigated, rather than unknown confounders.
      AIM: We aimed to investigate treatment fidelity (for the purpose of this paper,
      hereafter referred to as intervention fidelity), of an educational intervention
      delivered to general practice teams and designed to improve the primary care
      management of insomnia. METHOD: We conducted telephone interviews with patients
      and practitioners participating in the intervention arm of the trial to explore
      trial fidelity. Qualitative analysis was undertaken using constant comparison and
      a priori themes (categories): 'adherence to the delivery of the intervention',
      'patients received and understood intervention' and 'patient enactment'. RESULTS:
      If the intervention protocol was not adhered to by the practitioner then patient
      receipt, understanding and enactment levels were reduced. Recruitment
      difficulties in terms of the gap between initially being recruited into the study
      and attending an intervention consultation also reduced the effectiveness of the
      intervention. Patient attributes such as motivation to learn and engage
      contributed to the success of the uptake of the intervention. CONCLUSION:
      Qualitative methods using brief telephone interviews are an effective way of
      collecting the depth of data required to assess intervention fidelity.
      Intervention fidelity monitoring should be an important element of definitive
      trial design. TRIAL REGISTRATION: ClinicalTrials. gov id isrctn 55001433 -
      www.controlled-trials.com/isrctn55001433.

PMID- 24589149
TI  - Expanding capacity for supervision in general practice through student-engaged
      clinical audit.
AB  - BACKGROUND: Expanding clinical teaching opportunities is essential for securing a
      sustainable health workforce. Although Tasmanian general practitioners (GPs) are
      keen to provide learning opportunities for medical students, they have identified
      time pressures due to a need to meet patient service demand and a need for more
      guidance on effective clinical teaching, as factors impacting their ability to
      increase clinical supervision. By developing a clinical audit activity, we
      delivered an educational resource that did not require direct GP supervision yet
      provided meaningful learning outcomes for students. Through systematically
      reviewing patient records it was hoped that students would strengthen practice
      based quality improvement activities, thus 'giving back' to their placement
      practice. METHODS: A clinical audit curriculum was developed for fourth-year
      medical students at the Launceston Clinical School (n = 46) and implemented
      during their general practice rotation. This included a lecture and tutorial, and
      structured activities based on an audit of diabetes care. Preparation and support
      was provided to GP supervisors and practice staff through ongoing practice visits
      conducted by school academics. Implementation of the curriculum within general
      practice was evaluated through focus groups conducted with staff from five
      training practices (n = 29). Evaluation of student experiences is ongoing.
      RESULTS: This paper reports on the experiences of general practice supervisors
      and other practice staff. GPs and practice staff responded positively, indicating
      that the syllabus provided novel teaching opportunities and a modest contribution
      to improving patient records and patient care. Major learning opportunities
      identified included the development of skills working with patient records and
      practice software, and understanding the importance of accurate and reliable
      medical records for the optimal delivery of patient care. CONCLUSIONS: Conducting
      clinical audit provides students with novel learning opportunities while also
      strengthening the capacity of teaching general practices to provide clinical
      placements. Students learnt about the importance of monitoring professional
      practice using systematic clinical audit, and the complexities of managing
      patients within primary care. In so doing, they enhanced the robustness and rigor
      of patient records within their placement practice.

PMID- 24589150
TI  - The Kuwait-Scotland eHealth Innovation Network (KSeHIN): a sustainable approach
      to quality improvement in healthcare.
AB  - BACKGROUND: The rising prevalence of obesity and diabetes in Kuwait represents a
      significant challenge for the country's healthcare system. Diabetes care in
      Scotland has improved by adopting a system of managed clinical networks supported
      by a national informatics platform. In 2010, a Kuwait-Dundee collaboration was
      established with a view to transforming diabetes care in Kuwait. This paper
      describes the significant progress that has been made to date. METHODS: The
      Kuwait-Scotland eHealth Innovation Network (KSeHIN) is a partnership among
      health, education, industry and government. KSeHIN aims to deliver a package of
      clinical service development, education (including a formal postgraduate
      programme and continuing professional development) and research underpinned by a
      comprehensive informatics system. RESULTS: The informatics system includes a
      disease registry for children and adults with diabetes. At the patient level, the
      system provides an overview of clinical and operational data. At the population
      level, users view key performance indicators based on national standards of
      diabetes care established by KSeHIN. The national childhood registry (CODeR)
      accumulates approximately 300 children a year. The adult registry (KHN),
      implemented in four primary healthcare centres in 2013, has approximately 4000
      registered patients, most of whom are not yet meeting national clinical targets.
      A credit-bearing postgraduate educational programme provides module-based
      teaching and workplace-based projects. In addition, a new clinical skills centre
      provides simulator-based training. Over 150 masters students from throughout
      Kuwait are enrolled and over 400 work-based projects have been completed to date.
      CONCLUSION: KSeHIN represents a successful collaboration between multiple
      stakeholders working across traditional boundaries. It is targeting patient
      outcomes, system performance and professional development to provide a
      sustainable transformation in the quality of diabetes healthcare for the growing
      population of Kuwaitis with diabetes in Kuwait.

PMID- 24589151
TI  - Results of a phase I/II clinical trial: standardized, non-xenogenic, cultivated
      limbal stem cell transplantation.
AB  - BACKGROUND: To determine if a standardized, non-xenogenic, reduced manipulation
      cultivation and surgical transplantation of limbal stem cell grafts is a safe and
      effective treatment option for patients with total and partial limbal stem cell
      deficiency. METHODS: In vitro cellular outgrowth and phenotype of the limbal
      epithelial cell and composite grafts were validated using a new protocol.
      Patients received either autologous (n = 15) or allogenic (n = 3) explants
      cultured using a standardized protocol free from xenogenic products. The
      resulting grafts were transplanted using a reduced manipulation surgical
      technique. RESULTS: The majority of cells (>50%) displayed a progenitor phenotype
      typified by positive immunofluorescence for ?Np63, CK14 and ABCG2 and low
      immunofluorescence for CK3/12 and desmoglein 3 proteins. The surgical protocol
      was designed to minimize manipulation and the graft itself was secured without
      sutures. The transplant recipients were followed for a mean of 24 months. Twelve
      of the 18 transplant recipients were graded as anatomically successful (67%),
      based on the defined success parameters. There was a significant reduction in
      corneal neovascularization, which was accompanied by an improvement in pain
      though not photophobia or central corneal opacity post transplant. The
      transplantation protocol showed no measureable effect on visual acuity.
      CONCLUSION: We conclude that this standardized culture system and surgical
      approach is safe and effective in reducing corneal neovascularization. The
      technique is free from animal contaminants and maintains a large proportion of
      progenitor cells. Although this technique did not improve visual function,
      restoring a functional epithelial cell layer and reducing corneal
      neovascularization provides an improved platform for a penetrating keratoplasty
      to ultimately improve visual function.

PMID- 24589152
TI  - Total ankle replacement in patients with haemophilia and virus infections--a safe
      alternative to ankle arthrodesis?
AB  - Despite reliable results of ankle fusion for advanced haemophilic arthropathy,
      total ankle replacement (TAR) may be functionally advantageous. There is only
      very limited literature data available on TAR in patients with haemophilia. The
      objective of this study is to evaluate the short- and mid-term results after TAR
      in patients with end-stage haemophilic ankle arthropathy and concomitant virus
      infections. In a retrospective study, results after eleven TAR in 10 patients
      with severe (n = 8) and moderate (n = 2) haemophilia (mean age: 49 +/- 7 years,
      range, 37-59) were evaluated at a mean follow-up of 3.0 years (range, 1.2-5.4).
      Nine patients were positive for hepatitis C, five were HIV-positive. Range of
      motion (ROM), AOFAS-hindfoot-score, pain status (visual analogue scale, VAS) as
      well as patient satisfaction were evaluated. In two cases deep prosthesis
      infection occurred leading to the removal of the implant. In the remaining eight
      patients the mean AOFAS score improved significantly from 21.5 to 68.0 points (P
      < 0.0005), the VAS score decreased significantly from 7.6 to 1.9 points (P <
      0.0005). ROM increased from 23.2 to 25.0 degrees (P = 0.51). At final follow-up
      all patients without any complications were satisfied with the postoperative
      results. Radiographic examination did not reveal any signs of prosthetic
      loosening. TAR is a viable surgical treatment option in patients with end-stage
      ankle osteoarthritis due to haemophilia. It provides significant pain relieve and
      high patient satisfaction. However, due to the increased risk of infection and
      lack of long-term results, TAR particularly in patients with severe haemophilia
      and virus infections should be indicated carefully. 

PMID- 24589153
TI  - [Diagnostic approach to vasospasm in the vertebrobasilar circulation: Usefulness
      of transcranial doppler].

PMID- 24589154
TI  - Training in intensive care medicine. A challenge within reach.
AB  - The medical training model is currently immersed in a process of change. The new
      paradigm is intended to be more effective, more integrated within the healthcare
      system, and strongly oriented towards the direct application of knowledge to
      clinical practice. Compared with the established training system based on
      certification of the completion of a series or rotations and stays in certain
      healthcare units, the new model proposes a more structured training process based
      on the gradual acquisition of specific competences, in which residents must play
      an active role in designing their own training program. Training based on
      competences guarantees more transparent, updated and homogeneous learning of
      objective quality, and which can be homologated internationally. The tutors play
      a key role as the main directors of the process, and institutional commitment to
      their work is crucial. In this context, tutors should receive time and specific
      formation to allow the evaluation of training as the cornerstone of the new
      model. New forms of objective summative and training evaluation should be
      introduced to guarantee that the predefined competences and skills are
      effectively acquired. The free movement of specialists within Europe is very
      desirable and implies that training quality must be high and amenable to
      homologation among the different countries. The Competency Based training in
      Intensive Care Medicine in Europe program is our main reference for achieving
      this goal. Scientific societies in turn must impulse and facilitate all those
      initiatives destined to improve healthcare quality and therefore specialist
      training. They have the mission of designing strategies and processes that favor
      training, accreditation and advisory activities with the government authorities.

PMID- 24589155
TI  - Microvascular glycocalyx dimension estimated by automated SDF imaging is not
      related to cardiovascular disease.
AB  - OBJECTIVE: The EG regulates vascular homeostasis and has anti-atherogenic
      properties. SDF imaging allows for noninvasive visualization of microvessels and
      automated estimation of EG dimensions. We aimed to assess whether
      microcirculatory EG dimension is related to cardiovascular disease. METHODS:
      Sublingual EG dimension was estimated by SDF imaging in healthy volunteers and in
      patients visiting an outpatient clinic for vascular medicine of a university
      hospital in Amsterdam, the Netherlands. EG dimension was compared among healthy
      volunteers, patients with CVD, and patients at low (<10%) or high risk (>= 10%)
      of CVD according to the Framingham algorithm. RESULTS: In total 120 patients and
      30 healthy volunteers were included. Patients had a mean age of 59 +/- 14 years,
      71 (59%) were men and 24 (20%) were black. Healthy volunteers were on average 28
      +/- 4 years and 19 (63%) were men. EG dimension was similar in healthy volunteers
      (2.04 +/- 0.23 MUm), low-risk patients (2.05 +/- 0.24 MUm, n = 39), high-risk
      patients (2.05 +/- 0.23 MUm, n = 30) and in patients with CVD (2.09 +/- 0.21 MUm,
      n = 51, p = 0.79). EG dimension was not correlated with cardiovascular risk
      factors. CONCLUSIONS: Microcirculatory EG dimension, as estimated by automated
      SDF imaging, is not associated with CVD, suggesting that this technique may not
      contribute to cardiovascular risk stratification.

PMID- 24589156
TI  - Pralatrexate alone or in combination with bexarotene: long-term tolerability in
      relapsed/refractory mycosis fungoides.
AB  - BACKGROUND: This study aimed to assess the long-term tolerability of pralatrexate
      alone or in combination with oral bexarotene for relapsed or refractory mycosis
      fungoides (MF). PATIENTS AND METHODS: Patients with MF in this report were
      participants in 1 of 2 multicenter trials. During the dose-ranging phase I/II
      study, participants were treated with pralatrexate alone for 3 of 4 weeks. During
      a second phase I/II dose-ranging combination trial, participants were treated
      with pralatrexate at 15 mg/m(2)/wk for 3 of 4 weeks combined with 150 to 300
      mg/m(2) of daily oral bexarotene. RESULTS: Twenty-six patients were enrolled at
      our center, including 12 receiving pralatrexate and 14 receiving pralatrexate
      plus bexarotene. Four of 12 patients (33%) treated with pralatrexate alone
      responded. Of 14 patients treated with bexarotene plus pralatrexate, 7 (50%)
      responded. Ten participants, with a median age of 71 years (range, 41-82 years),
      received more than 9 cycles of pralatrexate, including 3 receiving pralatrexate
      and 7 receiving combination therapy. Median time to response was 15.75 weeks
      (range, 4-24 weeks), and the median duration of response was 26.75 weeks (range,
      8.5-49.5 weeks). The most common adverse event (AE) was mucositis in 8 (80%)
      patients. Other AEs of any grade included arthralgias (n = 1), headache (n = 1),
      neutropenia (n = 5), and skin necrosis (n = 2). Two patients initially had lower
      leg tumors that responded to therapy, leaving residual chronic leg ulcers.
      CONCLUSION: Pralatrexate alone or in combination with low-dose oral bexarotene is
      well tolerated and capable of providing long-term responses in patients of
      advanced age with advanced-stage MF.

PMID- 24589157
TI  - Extramedullary B lymphoblastic leukemia/lymphoma (B-ALL/B-LBL): a diagnostic
      challenge.

PMID- 24589158
TI  - Potential Intercontinental Movement of Influenza A(H7N9) Virus into North America
      by Wild Birds: Application of a Rapid Assessment Framework.
AB  - A critical question surrounding emergence of novel strains of avian influenza
      viruses (AIV) is the ability for wild migratory birds to translocate a complete
      (unreassorted whole genome) AIV intercontinentally. Virus translocation via
      migratory birds is suspected in outbreaks of highly pathogenic strain A(H5N1) in
      Asia, Africa and Europe. As a result, the potential intercontinental
      translocation of newly emerging AIV such as A(H7N9) from Eurasia to North America
      via migratory movements of birds remains a concern. An estimated 2.91 million
      aquatic birds move annually between Eurasia and North America with an estimated
      AIV prevalence as high as 32.2%. Here, we present a rapid assessment to address
      the likelihood of whole (unreassorted)-genome translocation of Eurasian strain
      AIV into North America. The scope of this assessment was limited specifically to
      assess the weight of evidence to support the movement of an unreassorted AIV
      intercontinentally by migratory aquatic birds. We developed a rapid assessment
      framework to assess the potential for intercontinental movement of avian
      influenzas by aquatic birds. This framework was iteratively reviewed by a
      multidisciplinary panel of scientific experts until a consensus was established.
      Our assessment framework identified four factors that may contribute to the
      potential for introduction of any AIV intercontinentally into North America by
      wild aquatic birds. These factors, in aggregate, provide a framework for
      evaluating the likelihood of new forms of AIV from Eurasia to be introduced by
      aquatic birds into North America. Based on our assessment, we determined that the
      potential for introduction of A(H7N9) into North America through aquatic
      migratory birds is possible, but the likelihood ranges from extremely low to low.

PMID- 24589159
TI  - Enhanced response using a multicomponent urine alarm treatment for nocturnal
      enuresis.
AB  - PURPOSE: The current study investigated the effects of using the combination of a
      urine alarm and simple reward system to treat nocturnal enuresis (NE) for three
      children who failed to fully respond to the urine alarm alone. DESIGN AND
      METHODS: A withdrawal design (i.e., ABACA) embedded within a delayed multiple
      baseline design across participants was used to evaluate the effects of the urine
      alarm alone and in combination with a reward system on participants' frequency of
      wet nights per week. Results were analyzed through visual and descriptive
      methods. RESULTS: The urine alarm in combination with a reward system resulted in
      improvements in all three participants' NE. These results are contrasted with the
      urine alarm alone, which produced less frequent dry nights. PRACTICE
      IMPLICATIONS: Nursing professionals in primary care settings are positioned to
      provide evidence-based treatment recommendations to families with children with
      NE. Findings from the current study provide a promising approach to the treatment
      of NE for those children who fail to respond fully to the urine alarm.

PMID- 24589161
TI  - Diameter change of common femoral arteries after percutaneous endovascular aortic
      repair with the use of the preclose technique.
AB  - OBJECTIVE: One of the major concerns regarding the preclose technique is its
      influence on the diameter of the accessed common femoral artery (CFA). The aim of
      our study was to evaluate the CFA diameter change after percutaneous endovascular
      aortic repair (PEVAR) with the use of the preclose technique. METHODS: From
      February 2012 to September 2013, 192 patients who underwent PEVAR with the
      preclose technique were reviewed. The patients were followed postoperatively with
      computed tomographic angiography 1, 6, and 12 months after PEVAR, and only those
      with complete computed tomography studies were included. For each access site,
      the inner diameter (ID) and outer diameter (OD) of the CFA were measured, and the
      diameters at various time periods were compared. In addition, the patient cohort
      was divided into four subgroups according to two parameters: the sheath size (12
      16F and 18-24F) and the number of closure devices used for the preclose technique
      (two devices, more than two devices). The differences in diameter change between
      the subgroups were analyzed. The significance of the diameter change and the
      influences of the two parameters were analyzed statistically with the use of the
      paired t-test, one-way analysis of variance, and two-way analysis of variance.
      RESULTS: Fifty-eight patients fulfilled the study criteria. No significant
      influence on the ID of the accessed CFAs was observed at baseline and 1, 6, and
      12 months (9.0 +/- 1.75 mm, 9.1 +/- 1.70 mm, 8.9 +/- 1.72 mm, and 9.0 +/- 1.68
      mm, respectively). By contrast, a significant increase in initial OD occurred 1
      month after PEVAR but gradually decreased in size in the following 11 months
      (13.0 +/- 2.37 mm, 16.4 +/- 3.44 mm, 14.2 +/- 3.06 mm, and 13.5 +/- 2.42 mm,
      respectively). Both the sheath size and the number of closure devices
      significantly affected the OD change (P < .001 and P = .037, respectively). The
      effect produced by the number of closure devices extended to 6 months after
      PEVAR, but the effect of the sheath size ceased before that time. CONCLUSIONS:
      This study demonstrates that PEVAR with the use of the preclose technique does
      not influence the ID of the accessed CFA, whereas the OD changes gradually over 1
      year. These results may indicate that future endovascular interventions can be
      performed with the use of the same access without the risk of vascular narrowing.

PMID- 24589160
TI  - National trends in utilization, mortality, and survival after repair of type B
      aortic dissection in the Medicare population.
AB  - OBJECTIVE: The application of thoracic endovascular aortic repair (TEVAR) has
      changed treatment paradigms for thoracic aortic disease. We sought to better
      define specific treatment patterns and outcomes for type B aortic dissection
      treated with TEVAR or open surgical repair (OSR). METHODS: Medicare patients
      undergoing type B thoracic aortic dissection repair (2000-2010) were identified
      by use of a validated International Classification of Diseases, Ninth Revision
      diagnostic and procedural code-based algorithm. Trends in utilization were
      analyzed by procedure type (OSR vs TEVAR), and patterns in patient
      characteristics and outcomes were examined. RESULTS: Total thoracic aortic
      dissection repairs increased by 21% between 2000 and 2010 (2.5 to 3 per 100,000
      Medicare patients; P = .001). A concomitant increase in TEVAR was seen during the
      same interval (0.03 to 0.8 per 100,000; P < .001). By 2010, TEVAR represented 27%
      of all repairs. TEVAR patients had higher rates of comorbid congestive heart
      failure (12% vs 9%; P < .001), chronic obstructive pulmonary disease (17% vs 10%;
      P < .001), diabetes (8% vs 5%; P < .001), and chronic renal failure (8% vs 3%; P
      < .001) compared with OSR patients. For all repairs, patient comorbidity burden
      increased over time (mean Charlson comorbidity score of 0.79 in 2000, 1.10 in
      2010; P = .04). During this same interval, in-hospital mortality rates declined
      from 47% to 23% (P < .001), a trend seen in both TEVAR and OSR patients. Whereas
      in-hospital mortality rates and 3-year survival were similar between patients
      selected for TEVAR and OSR, there was a trend toward women having slightly lower
      3-year survival after TEVAR (60% women vs 63% men; P = .07). CONCLUSIONS:
      Surgical treatment of type B aortic dissection has increased over time,
      reflecting an increase in the utilization of TEVAR. Overall, type B dissection
      repairs are currently performed at lower mortality risk in patients with more
      comorbidities.

PMID- 24589162
TI  - The impact of stent graft evolution on the results of endovascular abdominal
      aortic aneurysm repair.
AB  - OBJECTIVE: There have been four eras in the development of endovascular aneurysm
      repair (EVAR): physician-made grafts, early industry devices, intermediary
      commercial endografts, and modern stent grafts. This study analyzes differences
      in outcomes between these four groups and the impact of device evolution and
      increased physician experience. METHODS: From 1992 to 2012, 1380 patients
      underwent elective EVAR. Fourteen different devices were used during this time.
      The four generations were defined as follows: era 1, all physician-made devices;
      era 2, June 1994 to June 2003; era 3, June 2003 to January 2008; and era 4,
      January 2008 to July 2012. Grafts used in each era were the following: era 1,
      physician made; era 2, early industry, such as EVT, Talent, AneuRx, Excluder,
      Quantum LP, Vanguard, Ancure, and Teramed; era 3, Talent, Endologix, Excluder,
      AAAdvantage, Zenith, and Aptus; and era 4, Zenith, Endurant, and Excluder.
      RESULTS: Mean age was 75.2 years, and 84.5% were men. Adjunctive procedures
      decreased from era 1 to era 2 (P < .001) but rose again in eras 3 and 4 (P <
      .001). Procedure times (P < .001), blood loss (P < .001), and length of stay (P <
      .001) have decreased in eras 2, 3, and 4 compared with era 1. Major perioperative
      complications (era 1, 23%; era 2, 5.9%; era 3, 4.9%; and era 4, 4.7%; P < .001),
      abdominal aortic aneurysm-related perioperative mortality (era 1, 4.3%; era 2,
      0.2%; era 3, 0.06%; and era 4, 0.5%; P < .001), and all-cause perioperative
      mortality (era 1, 7.7%; era 2, 1.9%; era 3, 1.5%; and era 4, 0.47%; P < .001)
      have also decreased in eras 2, 3, and 4 compared with era 1. Type I and type III
      endoleaks (P < .001) and the need for reintervention (P < .001) have decreased.
      Freedom from aneurysm-related mortality has significantly improved. CONCLUSIONS:
      EVAR has evolved during the last 20 years, resulting in an improvement in
      efficiency, outcomes, and procedural success. The most significant advance is
      seen in the transition from era 1 to the later eras.

PMID- 24589163
TI  - Is being homeless or worried about housing associated with allergies and skin
      problems?

PMID- 24589164
TI  - Response to the "Allergen of the month--Melaleuca".

PMID- 24589165
TI  - A critical appraisal of omalizumab as a therapeutic option for chronic refractory
      urticaria/angioedema.

PMID- 24589166
TI  - Allergic rhinitis quality of life in urban children with asthma.
AB  - BACKGROUND: Urban children with asthma and allergic rhinitis (AR) are at risk for
      experiencing worse AR-related quality of life (QOL). Although AR may be
      underdiagnosed and undertreated in urban minority children, research has not
      considered which illness-related indicators (eg, AR control) may contribute to AR
      QOL in this population. OBJECTIVE: To examine associations among AR control,
      asthma control, allergy symptoms, asthma symptoms, and AR QOL in a sample of 195
      urban caregivers and their children with asthma (7-9 years of age) from African
      American, Latino, and non-Latino white backgrounds. Racial and ethnic differences
      in AR QOL were also examined. METHODS: Families resided in 1 of 4 cities selected
      as recruitment sources because of their high concentrations of ethnic minority
      and non-Latino white, urban families. Caregivers and children completed a series
      of interview-based and clinician-based assessments across one academic year and 4
      week periods to track daily asthma and nasal symptoms. RESULTS: Better AR control
      was associated with higher AR QOL (beta = -.32, P < .01) and all QOL subscales.
      AR control predicted AR QOL over and above asthma control (beta = -.28, P < .01).
      Controlling for AR control, non-Latino white children reported better QOL related
      to practical problems than both Latino and African American children (P < .05).
      CONCLUSION: Findings suggest that strategies to enhance AR control in urban
      children with asthma may assist in improving AR QOL. Non-Latino white children
      may experience less impairment of their AR QOL because of practical problems (eg,
      blow nose) than African American or Latino children with asthma.

PMID- 24589168
TI  - Knowledge is power.

PMID- 24589167
TI  - Development of a PCR assay and pyrosequencing for identification of important
      human fish-borne trematodes and its potential use for detection in fecal
      specimens.
AB  - BACKGROUND: Small liver and minute intestinal flukes are highly prevalent in
      Southeast Asia. Definitive diagnosis of parasite infection is usually achieved
      parasitologically by finding the fluke eggs in feces. However, their eggs are
      difficult to differentiate morphologically in fecal samples, even for experienced
      technicians. The present study developed a PCR assay coupled with DNA
      pyrosequencing for identification of the fish-borne trematodes (FBT),
      Opisthorchis viverrini, Clonorchis sinensis, Haplorchis taichui, H. pumilio and
      Stellantchasmus falcatus, and to evaluate potential detection in fecal specimens,
      and identification and differentiation of cercarial and metacercarial stages.
      METHODS: Primers targeting the partial 28S large subunit ribosomal RNA gene were
      designed and about 46-47 nucleotides were selected as the target region for
      species identification by a PCR assay coupled with a pyrosequencing technique.
      RESULTS: The nucleotide variations at 24 positions, which is sufficient for the
      identification of the five species of FBT were selected. The method could
      identify O. viverrini and C. sinensis eggs in feces, cercarial and metacercarial
      stages of O. viverrini, and metacercarial stage of H. pumilio and H. taichui. The
      detection limit was as little as a single O. viverrini or C. sinensis egg
      artificially inoculated in 100 mg of non-infected fecal sample (equivalent to 10
      eggs per gram), indicating highly sensitivity. The method was found to be
      superior to the traditional microscopy method and was more rapid than Sanger DNA
      sequencing. CONCLUSIONS: DNA pyrosequencing-based identification is a valuable
      tool for differentiating O. viverrini and other Opisthorchis-like eggs, and can
      be applied to epidemiological studies and for molecular taxonomic investigation
      of FBT in endemic areas.

PMID- 24589170
TI  - Death by testosterone? We think not!

PMID- 24589171
TI  - Micro-bubble transcranial Doppler ultrasound for exclusion of right-to-left
      circulatory shunts: why should we provide the service?
AB  - Micro-bubble transcranial Doppler ultrasound is a study used for the
      identification and quantification of a right-to-left circulatory shunt which can
      be implicated in stroke. It is an underused technique in many centres. Micro
      bubble transcranial Doppler ultrasound is non-invasive, innocuous, quick and
      requires no fasting or sedation. Published literature also suggests almost
      perfect concordance with transoesophageal echocardiography and potentially
      greater sensitivity. We believe there is a great potential for neuroradiologists
      to provide this service as part of the diagnostic workup in patients with
      cryptogenic stroke. 

PMID- 24589172
TI  - Effective policy initiatives to constrain lipid-lowering drug expenditure growth
      in South Korea.
AB  - BACKGROUND: The rapid growth of prescription drug expenditures is a major problem
      in South Korea. Accordingly, the South Korean government introduced a positive
      listing system in 2006. They also adopted various price reduction policies.
      Nevertheless, the total expenditure for lipid-lowering drugs have steadily
      increased throughout South Korea. The present study explores the factors that
      have influenced the increased expenditures of lipid-lowering drugs with a
      particular focus on the effects of statins in this process. METHODS: This paper
      investigates the National Health Insurance claims data for prescribed lipid
      lowering drugs collected between January 1, 2005 and December 31, 2009. We
      specifically focused on statins and assessed the yearly variation of statin
      expenditure by calculating the increased rate of paired pharmaceutical
      expenditures over a 2 year period. Our study classified statins into three
      categories: new entrants, core medicines and exiting medicines. For core
      medicines, we further examined influencing factors such as price, amount of drugs
      consumed by volume, and prescription changes (substitutes for other drug).
      RESULTS: Statin expenditure showed an average annual increase of 25.7% between
      2005 and 2009. Among the different statins, the expenditure of atorvastatin
      showed a 36.6% annual increase rate, which was the most dramatic among all
      statins. Also we divided expenditure for core medicines by the price factor,
      volume factor, and prescription change. The result showed that annual weighted
      average prices of individual drug decreased each year, which clearly showed that
      price influenced statin expenditure in a negative direction. The use of generic
      drugs containing the same active ingredient as name-brand drugs increased and
      negatively affected statin expenditure (Generic Mix effect). However, the use of
      relatively expensive ingredients within statin increase, Ingredient Mix effect
      contributed to increased statin expenditure (Ingredient Mix effect). In
      particular, the volume effect was found to be critical for increasing statin
      expenditure as the amount of statin consumed increased steadily throughout the
      study period. CONCLUSIONS: The recent rapid increase in statin expenditure can
      largely be attributed to an increase in consumption volume. In order to check
      drug expenditures effectively in our current situation, in which chronic diseases
      remain steadily on the rise, it is necessary to not only have supply-side
      initiatives such as price reduction, but also demand-side initiatives that could
      control drug consumption volume, for example: educational programs for rational
      prescription, generic drug promotional policies, and policies providing
      prescription targets.

PMID- 24589175
TI  - Editorial: is there a place for the formocresol pulpotomy? Indirect pulp capping,
      the real alterative.

PMID- 24589174
TI  - Perspectives of paediatric and adult gastroenterologists on transfer and
      transition care of adolescents with inflammatory bowel disease.
AB  - BACKGROUND: Programmes specific to inflammatory bowel disease (IBD) that
      facilitate transition from paediatric to adult care are currently lacking. AIM:
      We aimed to explore the perceived needs of adolescents with IBD among paediatric
      and adult gastroenterologists and to identify barriers to effective transition.
      METHODS: A web-based survey of paediatric and adult gastroenterologists in
      Australia and New Zealand employed both ranked items (Likert scale; from 1 not
      important to 5 very important) and forced choice items regarding the importance
      of various factors in facilitating effective transition of adolescents from
      paediatric to adult care. RESULTS: Response rate among 178 clinicians was 41%.
      Only 23% of respondents felt that adolescents with IBD were adequately prepared
      for transition to adult care. Psychological maturity (Mean = 4.3, standard
      deviation (SD) = 0.70) and readiness as assessed by adult caregiver (Mean = 4, SD
      = 0.72) were prioritised as the most important factors in determining timing of
      transfer. Self-efficacy and readiness as assessed by adult caregiver were
      considered the two most important factors to determine timing of transition by
      both groups of gastroenterologists. Poor medical and surgical handover (Mean =
      4.10, SD = 0.8) and patients' lack of responsibility for their own care (Mean=
      4.10, SD = 0.82) were perceived as major barriers to successful transition by
      both paediatric and adult gastroenterologists. CONCLUSIONS: Deficiencies exist in
      current transition care of adolescents with IBD in Australia and New Zealand.
      Standardising transition care practices with strategies aimed at optimising
      communication, patient education, self-efficacy and adherence may improve
      outcomes.

PMID- 24589176
TI  - Verbal fluency in cerebral small vessel disease and Alzheimer's disease.
AB  - Patterns of verbal fluency deficits have been explored across different
      neurodegenerative disorders. This study sought to investigate the specific
      pattern of verbal fluency performance in cerebral small vessel disease (SVD),
      which is the most common cause of vascular cognitive impairment, and compare this
      with Alzheimer's disease (AD). Participants with SVD (n = 45), AD (n = 24) and
      healthy controls (n = 80) completed assessments of semantic and phonemic fluency.
      Mixed-model analyses of covariance were used to compare performance on the
      different fluency tasks between the groups, and a discriminant function analysis
      was conducted to examine group differentiation. The SVD group was impaired in
      both fluency tasks when compared to the controls. In contrast, the AD group
      displayed impairment in semantic fluency only. Discriminant function analysis
      revealed that fluency scores correctly classified 80% of SVD patients and 92% of
      AD patients. The pattern of performance observed in the SVD group may reflect
      deficits in executive function and processing speed impacting equivalently on
      semantic and phonemic fluency. The differences between the SVD and AD groups
      highlighted in this study may be useful for distinguishing between these
      conditions.

PMID- 24589177
TI  - The impact of stillbirth on consultant obstetrician gynaecologists: a qualitative
      study.
AB  - OBJECTIVE: To explore the personal and professional impact of stillbirth on
      consultant obstetrician gynaecologists. DESIGN: Semi-structured in-depth
      qualitative interviews. SETTING: A tertiary university maternity hospital in
      Ireland with a birth rate of c. 9000 per annum and a stillbirth rate of 4.6/1000.
      SAMPLE: Purposive sample of eight consultant obstetrician gynaecologists (50% of
      consultant obstetrician gynaecologists in the hospital). METHODS: Semi-structured
      in-depth interviews analysed by Interpretative Phenomenological Analysis. (IPA)
      IPA is a methodology for exploring human experience and its meaning for the
      individual. MAIN OUTCOME MEASURES: The lived experiences, personal feelings and
      professional impact of stillbirth on consultant obstetrician gynaecologists.
      RESULTS: Stillbirth was identified as amongst the most difficult experiences for
      consultants. Two superordinate themes emerged: the human response to stillbirth
      and the weight of responsibility. The human response to stillbirth was
      characterised by the personal impact of stillbirth for consultants and, in turn,
      how that shapes the care they provide. The weight of professional responsibility
      was characterised by the sense of professional burden and the possibility of a
      medico-legal challenge-mostly for those who are primarily gynaecologists
      resulting in the question 'what have I missed?'. CONCLUSIONS: Despite the impact
      of stillbirth, no consultant has received formal training in perinatal
      bereavement care. This study highlights a gap in training and the significant
      impact of stillbirth on obstetricians, professionally and personally. The
      provision of support, ongoing education, bereavement training and self-care is
      recommended. Medico-legal concerns following stillbirth potentially impact on
      care, warranting further research.

PMID- 24589178
TI  - Predictive factors for incidental gallbladder dysplasia and carcinoma.
AB  - BACKGROUND: This study aims to analyze clinical characteristics and demographics
      of all patients admitted for cholecystectomy in a tertiary referral center to
      determine predictors of incidental gallbladder dysplasia (IGBD) and incidental
      gallbladder carcinoma (IGBC). METHODS: A retrospective analyses of clinical,
      demographic, and histologic features of patients undergoing cholecystectomy in a
      single tertiary institution from 2005-2012 were performed using a logistic
      regression model to determine the predictors of IGBD and IGBC. RESULTS: Some 771
      (28 conversions to open surgery [3.6%]) and 93 patients (10.7%) underwent
      laparoscopic and open cholecystectomies for gallstone disease, respectively. At
      final pathology, IGBD (low-grade [n = 10], high-grade [n = 2], mixed-grade [n =
      1], and adenoma-associated [n = 5] dysplasia) was found in 18 patients (2%;
      median age, 45 y; interquartile range, 42.5-63.5; male-to-female ratio, 1:2; six
      Caucasian; and 12 Asian). IGBC was found in seven patients (0.8%; median age, 69
      y; interquartile range, 69-72; one Afro-Caribbean; four Caucasian; and two
      Asian). Logistic regression analysis revealed Asian patients to be at a higher
      risk of IGBD (odds ratio [OR], 2.9; 95% confidence interval [CI], 1.1-8.0; P =
      0.02). Only age (OR, 1.12; 95% CI, 1.04-1.2; P < 0.01) and polypoid lesions (OR,
      37.4; 95% CI, 2.97-470.6; P = 0.01) were significantly associated with IGBC.
      Receiver operating characteristic curve analysis demonstrated that age >68 y
      correlated positively to IGBC. CONCLUSIONS: IGBD and IGBC are fairly common
      incidental histologic finding after cholecystectomy for gallstone disease. When
      considering cholecystectomy, patients' demographics, in particular age and race,
      should always be considered as this might help the surgeon and the pathologist to
      institute the appropriate treatment.

PMID- 24589179
TI  - Ischemic preconditioning improves liver tolerance to congestion-reperfusion
      injury in mice.
AB  - BACKGROUND: Congestion-reperfusion injury (CRI) is a common complication after
      living donor liver transplantation, which has not been fully understood. It
      causes more severe inflammatory response as compared with ischemia-reperfusion
      injury (IRI). Ischemic preconditioning (IPC) has been endowed with powerful
      protective properties toward IRI. This study aimed to investigate whether IPC
      also has a protective effect against CRI and potential underlying mechanisms.
      MATERIALS AND METHODS: Mice were randomly divided into sham operation, CRI, IPC
      CRI, and congestion precondition (CPC-CRI) group. The hepatic vein of the left
      anterior hepatic lobe was occluded for 75 min followed by reperfusion in the CRI
      group. The blood inflow was previously clamped for 10 min followed by 10 min of
      reperfusion just before occluding the hepatic vein in the IPC-CRI group. To
      imitating IPC in the CPC-CRI group, 10 min of congestion followed by 10 min of
      reperfusion just before CRI was performed. The animals were sacrificed at 2, 6,
      24, 48 h, and 7 d after reperfusion. The blood and liver samples were collected
      for hepatic function assay, histology, terminal deoxynucleotidyl transferase dUTP
      nick end labeling, myeloperoxidase, and real-time polymerase chain reaction
      analysis. RESULTS: Mice in the CRI, IPC-CRI, and CPC-CRI group demonstrated
      elevated liver enzymes, histologic damage, cellular apoptosis, and inflammatory
      response compared with those in the sham operation group. Compared with the CRI
      group, mice in the IPC-CRI group expressed lower alanine transaminase activities
      (2 h: 839.2 +/- 132.5 versus 384.2 +/- 94.8, P < 0.01; and 6 h: 680 +/- 142.4
      versus 342.3 +/- 99.7, P < 0.01) and lower myeloperoxidase levels (2 h: 7.1 +/-
      4.0 U/g versus 3.8 +/- 1.6 U/g, P < 0.05; and 6 h: 8.1 +/- 1.3 U/g versus 5.2 +/-
      3.0 U/g, P < 0.05). However, the alanine transaminase level in the CPC-CRI group
      was notably higher at 2 h (839.2 +/- 132.5 versus 1087.5 +/- 192.5, P < 0.05).
      Livers from mice in the IPC-CRI group showed better tissue integrity, diminished
      hepatocellular injury, and apoptosis at 2 and 6 h. The messenger RNA
      transcriptions of interleukin 1 and interleukin 6 were significantly lower after
      2-24 h of reperfusion, whereas tumor necrosis factor alpha and monocyte
      chemoattractant protein 1 were significantly lower after 24 h of reperfusion in
      the IPC-CRI group. CONCLUSIONS: IPC can significantly improve liver tolerance to
      CRI by attenuating neutrophil infiltration, proinflammatory cytokine formation,
      and hepatocytes apoptosis. This pretreatment strategy holds greater prospect of
      being translated into clinical use in living donor liver transplantation.

PMID- 24589180
TI  - Sero-positivity rate of rubella and associated factors among pregnant women
      attending antenatal care in Mwanza, Tanzania.
AB  - BACKGROUND: Sero-positivity rates of the rubella virus among pregnant women vary
      widely throughout the world. In Tanzania, rubella vaccination is not included in
      the national immunization schedule and there is therefore no antenatal screening
      for this viral disease. So far, there are no reports on the sero-prevalence of
      rubella among pregnant women in Tanzania. As a result, this study was undertaken
      to establish the sero-positivity rate of rubella and rubella risk factors among
      pregnant women attending antenatal care clinics in Mwanza, Tanzania. METHODS:
      From November 2012 to May 2013 a total of 350 pregnant women were enrolled and
      their serum samples collected and analyzed using the AXSYM anti-rubella virus
      IgG/IgM-MEIA test. Demographic and clinical data were collected using a
      standardized data collection tool. Data analysis was done using STATA version 12.
      RESULTS: Of 342 pregnant women tested for rubella antibodies, 317 (92.6%) were
      positive for anti-rubella IgG while only 1 (0.3%) was positive for IgM. Higher
      sero-positivity rates were found in the age group of 25-44 years. Furthermore, it
      was observed that with each year increase in age, the risk of contracting rubella
      increases by 12% (OR = 1.12, 95% CI: 1.02-1.22, P = 0.019). Women involved in
      farming and business women were at a higher risk of contracting rubella infection
      compared to formally employed women (OR: 4.9, P = 0.011; OR 7.1, p = 0.003
      respectively). In univariate analysis, the risk of contracting rubella virus
      infection was found to increase with gestational age with a statistical
      significance. CONCLUSIONS: Sero-positivity rates of rubella are high in Mwanza
      and are significantly associated with an increase in age and being a farmer or a
      business woman. Screening of rubella and immunization of women at risk are highly
      recommended in this area with a high non-immune rate against rubella virus.

PMID- 24589181
TI  - Calreticulin protects rat microvascular endothelial cells against microwave
      radiation-induced injury by attenuating endoplasmic reticulum stress.
AB  - OBJECTIVE: This study was designed to evaluate whether exogenous CRT was
      beneficial for alleviating MR-induced injury by suppressing ER stress in rat
      MMECs. METHODS: MMECs were pretreated with CRT (25 pg/mL) for 12 hours, followed
      by the exposure to 2.856 GHz radiation at a mean power density of 30 mW/cm(2) for
      six minutes. MR-induced injury in MMECs was evaluated by LDH leakage, apoptosis,
      and cell viability analysis. The expression of GRP78, CRT, CHOP, Bcl-2, and Bax
      were examined by Western blot analysis to reflect ER stress response and ER
      stress-related apoptosis. RESULTS: MR induced marked MMECs injury, as shown by
      increased LDH leakage and apoptosis rate and decreased cell viability. MR also
      induced excessive ER stress, characterized by increased expression of GRP78 and
      CRT, and ER stress-related apoptotic signaling as well, as shown by the
      upregulation of CHOP and Bax and the downregulation of Bcl-2. Exogenous CRT
      pretreatment remarkably attenuated MR-induced cell apoptosis and LDH leakage, ER
      stress, and activation of the ER stress-related apoptotic signaling. CONCLUSIONS:
      Exogenous CRT attenuates MR-induced ER stress-related apoptosis by suppressing
      CHOP-mediated apoptotic signaling pathways in MMECs.

PMID- 24589182
TI  - A gene-specific non-enhancer sequence is critical for expression from the
      promoter of the small heat shock protein gene alphaB-crystallin.
AB  - BACKGROUND: Deciphering of the information content of eukaryotic promoters has
      remained confined to universal landmarks and conserved sequence elements such as
      enhancers and transcription factor binding motifs, which are considered
      sufficient for gene activation and regulation. Gene-specific sequences,
      interspersed between the canonical transacting factor binding sites or adjoining
      them within a promoter, are generally taken to be devoid of any regulatory
      information and have therefore been largely ignored. An unanswered question
      therefore is, do gene-specific sequences within a eukaryotic promoter have a role
      in gene activation? Here, we present an exhaustive experimental analysis of a
      gene-specific sequence adjoining the heat shock element (HSE) in the proximal
      promoter of the small heat shock protein gene, alphaB-crystallin (cryab). These
      sequences are highly conserved between the rodents and the humans. RESULTS: Using
      human retinal pigment epithelial cells in culture as the host, we have identified
      a 10-bp gene-specific promoter sequence (GPS), which, unlike an enhancer,
      controls expression from the promoter of this gene, only when in appropriate
      position and orientation. Notably, the data suggests that GPS in comparison with
      the HSE works in a context-independent fashion. Additionally, when moved
      upstream, about a nucleosome length of DNA (-154 bp) from the transcription start
      site (TSS), the activity of the promoter is markedly inhibited, suggesting its
      involvement in local promoter access. Importantly, we demonstrate that deletion
      of the GPS results in complete loss of cryab promoter activity in transgenic
      mice. CONCLUSIONS: These data suggest that gene-specific sequences such as the
      GPS, identified here, may have critical roles in regulating gene-specific
      activity from eukaryotic promoters.

PMID- 24589183
TI  - Fusion of bone marrow-derived cells with cancer cells: metastasis as a secondary
      disease in cancer.
AB  - This perspective article highlights the leukocyte-cancer cell hybrid theory as a
      mechanism for cancer metastasis. Beginning from the first proposal of the theory
      more than a century ago and continuing today with the first proof for this theory
      in a human cancer, the hybrid theory offers a unifying explanation for
      metastasis. In this scenario, leukocyte fusion with a cancer cell is a secondary
      disease superimposed upon the early tumor, giving birth to a new, malignant cell
      with a leukocyte-cancer cell hybrid epigenome. 

PMID- 24589184
TI  - Joint disease status of severe and moderate haemophilia patients at the Beijing
      Children's Hospital: early onset and rapid increasing severity of arthropathy in
      90% of patients by 6 years of age.

PMID- 24589185
TI  - [Family factors associated with co-dependency in nurses at a hospital in Cancun,
      Quintana Roo, Mexico].
AB  - OBJECTIVE: Identifying family factors associated with the presence of co
      dependency in nurses of a regional hospital in Cancun, Quintana Roo, Mexico.
      DESIGN: Cross-sectional, comparative study. LOCATION: City of Cancun (Mexico).
      PARTICIPANTS: A random sample of 200nurses who met the inclusion criteria (having
      a partner for over a year, to be at work on the day of the interview), and who
      gave informed consent, completed three questionnaires during different shifts.
      MAIN MEASUREMENTS: Age, educational level, socioeconomic status, type of family
      structure, life cycle stage, co-dependency and family functioning. RESULTS: A
      total of 200nurses, with mean age of 36+/-8years, took part. The most common
      socioeconomic status was high (48%), and 47.5% had graduate studies. A co
      dependency level of 20.5% (95%CI: 15-26.5) was found. Family factors associated
      with the presence of co-dependency were; family dysfunction, prevalence ratio
      (PR)=9.62 (95%CI: 3.47-27.3), stage of independence, PR=3.41 (95%CI: 1.44-7.86),
      single parent, PR=6.35 (95%CI: 2.41-16.68), and time with partner less than 5
      years, PR=3.41 (95%CI: 1.54-7.85). CONCLUSIONS: It was found that family
      dysfunction and being a single parent were significantly associated with co
      dependency in hospital nurses, therefore, on being able to identify these
      factors, family physicians can improve their dynamics and functioning by family
      study, and improving effective communication with nursing staff and their
      families.

PMID- 24589186
TI  - Influences shaping nurses' use of distraction for children's procedural pain.
AB  - PURPOSE: This study explored pediatric nurses' choices to use distraction for
      managing painful procedures. DESIGN AND METHODS: Using interpretive description
      approaches, interviews with pediatric nurses provided descriptions of choices to
      manage procedural pain. RESULTS: Nurses' distress influenced distraction use to
      mitigate the suffering of children and themselves. Newer nurses described task
      mastery as influencing distraction choices. Nurses' accounts of performing
      painful procedures on children mirrored children's descriptions of pain from the
      literature. PRACTICE IMPLICATIONS: Nurses' distress and competency performing
      painful procedures on children influenced practice. Future qualitative studies
      could extend understanding of pain management choices by pediatric nurses and the
      impact on undermanaged pain.

PMID- 24589187
TI  - Embolization of the hemorrhoidal arteries (the emborrhoid technique): a new
      concept and challenge for interventional radiology.
AB  - Elective transanal Doppler-guided hemorrhoidal artery ligation (DG-HAL) has
      recently been shown to be effective in hemorrhoidal disease. It consists of
      ligating the terminal branches of the superior rectal artery under Doppler
      guidance, in order to reduce the hemorrhoidal arterial blood flow and improve the
      symptoms. By analogy, we propose performing this arterial occlusion using the
      "emborrhoid" technique (embolization of the hemorrhoidal arteries), in which
      arterial occlusion is achieved via the endovascular route using coils placed in
      the terminal branches of the superior rectal arteries. Three patients have been
      treated by this new technique, and the observations show that it is feasible and
      reproducible, with no ischemic complications or pain. Additional studies are
      needed to evaluate the efficacy of this technique for the treatment of
      hemorrhoidal disease. 

PMID- 24589188
TI  - Magnetic resonance guided focalised ultrasound thermo-ablation: a promising
      oncologic local therapy.

PMID- 24589189
TI  - Retrograde cerebral venous air embolism: a rare cause of intracranial gas.

PMID- 24589191
TI  - Intercourse avoidance among women with coronary artery disease.
AB  - INTRODUCTION: Avoidance of sexual intercourse has not been frequently studied
      among patients with chronic medical conditions and patients with coronary artery
      disease (CAD) are not exception. AIM: We aimed to (i) compare intercourse
      avoidance during the past 2 weeks among women with CAD and healthy controls; and
      (ii) to determine factors associated with intercourse avoidance during the past 2
      weeks among women with CAD. METHODS: This study was conducted in an outpatient
      cardiology clinic in Tehran, Iran. The study included 152 married women with CAD
      and 50 controls. Socio-demographic and clinical data including the severity of
      angina (WHO Rose Questionnaire), risk factors (cigarette smoking, hyperlipidemia,
      diabetes, and obesity), fatigue, physical function (visual analogue scale [VAS])
      and somatic comorbidities [Ifudu index], symptoms of anxiety and depression
      (Hospital Anxiety and Depression Scale [HADS]), and dyadic adjustment (Revised
      Dyadic Adjustment Scale [R-DAS]) were considered as independent variables.
      Logistic regression was used to determine predictors of sexual avoidance during
      the past 2 weeks. MAIN OUTCOME MEASURES: The main outcome was intercourse
      avoidance over a 2-week period, measured by the Relation and Sexuality Scale
      (RSS). RESULT: Avoidance of intercourse during the past 2 weeks was higher among
      women with CAD than controls (73.0% vs. 56%, P = 0.024). According to the
      logistic regression, intercourse avoidance was positively associated with age
      (Odds ratio [OR] = 1.127, 95% confidence interval [CI] = 1.073, 1.185), somatic
      comorbidities (OR = 1.137, 95% CI = 1.061, 1.218) and depressive symptoms (OR =
      1.150, 95% CI = 1.022, 1.293). CONCLUSION: Our study suggests that among women
      with CAD, age, depressive symptoms and somatic comorbidities are associated with
      avoidance of intercourse. As having intercourse is safe among patients with
      stable CAD, all health professionals should discuss sexual behaviors with their
      female CAD patients, especially those that are older, with higher depressive
      symptoms or multiple comorbidities so as to allay fears about sexual functioning.

PMID- 24589190
TI  - Fast demographic traits promote high diversification rates of Amazonian trees.
AB  - The Amazon rain forest sustains the world's highest tree diversity, but it
      remains unclear why some clades of trees are hyperdiverse, whereas others are
      not. Using dated phylogenies, estimates of current species richness and trait and
      demographic data from a large network of forest plots, we show that fast
      demographic traits--short turnover times--are associated with high
      diversification rates across 51 clades of canopy trees. This relationship is
      robust to assuming that diversification rates are either constant or decline over
      time, and occurs in a wide range of Neotropical tree lineages. This finding
      reveals the crucial role of intrinsic, ecological variation among clades for
      understanding the origin of the remarkable diversity of Amazonian trees and
      forests.

PMID- 24589192
TI  - In vivo imaging of mice infected with bioluminescent Trypanosoma cruzi unveils
      novel sites of infection.
AB  - BACKGROUND: The development of techniques that allow the imaging of animals
      infected with parasites expressing luciferase opens up new possibilities for
      following the fate of parasites in infected mammals. METHODS: D-luciferin
      potassium salt stock solution was prepared in phosphate-buffered saline (PBS) at
      15 mg/ml. To produce bioluminescence, infected and control mice received an
      intraperitoneal injection of luciferin stock solution (150 mg/kg). All mice were
      immediately anesthetized with 2% isofluorane, and after 10 minutes were imaged.
      Ex vivo evaluation of infected tissues and organs was evaluated in a 24-well
      plate in 150 MUg/ml D-luciferin diluted in PBS. Images were captured using the
      IVIS Lumina image system (Xenogen). Dissected organs were also evaluated by
      microscopy of hematoxylin-eosin stained sections. RESULTS: Here we describe the
      results obtained using a genetically modified Dm28c strain of T. cruzi expressing
      the firefly luciferase to keep track of infection by bioluminescence imaging.
      Progression of infection was observed in vivo in BALB/c mice at various intervals
      after infection with transgenic Dm28c-luc. The bioluminescent signal was
      immediately observed at the site of T. cruzi inoculation, and one day post
      infection (dpi) it was disseminated in the peritoneal cavity. A similar pattern
      in the cavity was observed on 7 dpi, but the bioluminescence was more intense in
      the terminal region of the large intestine, rectum, and gonads. On 14 and 21 dpi,
      bioluminescent parasites were also observed in the heart, snout, paws, hind
      limbs, and forelimbs. From 28 dpi to 180 dpi in chronically infected mice,
      bioluminescence declined in regions of the body but was concentrated in the gonad
      region. Ex vivo evaluation of dissected organs and tissues by bioluminescent
      imaging confirmed the in vivo bioluminescent foci. Histopathological analysis of
      dissected organs demonstrated parasite nests at the rectum and snout, in muscle
      fibers of mice infected with Dm28c-WT and with Dm28c-luc, corroborating the
      bioluminescent imaging. CONCLUSION: Bioluminescence imaging is accurate for
      tracking parasites in vivo, and this methodology is important to gain a better
      understanding of the infection, tissue inflammation, and parasite biology
      regarding host cell interaction, proliferation, and parasite clearance to
      subpatent levels.

PMID- 24589193
TI  - Early infections by myxoma virus of young rabbits (Oryctolagus cuniculus)
      protected by maternal antibodies activate their immune system and enhance herd
      immunity in wild populations.
AB  - The role of maternal antibodies is to protect newborns against acute early
      infection by pathogens. This can be achieved either by preventing any infection
      or by allowing attenuated infections associated with activation of the immune
      system, the two strategies being based on different cost/benefit ratios. We
      carried out an epidemiological survey of myxomatosis, which is a highly lethal
      infectious disease, in two distant wild populations of rabbits to describe the
      epidemiological pattern of the disease. Detection of specific IgM and IgG enabled
      us to describe the pattern of immunity. We show that maternal immunity attenuates
      early infection of juveniles and enables activation of their immune system. This
      mechanism associated with steady circulation of the myxoma virus in both
      populations, which induces frequent reinfections of immune rabbits, leads to the
      maintenance of high immunity levels within populations. Thus, myxomatosis has a
      low impact, with most infections being asymptomatic. This work shows that
      infection of young rabbits protected by maternal antibodies induces attenuated
      disease and activates their immune system. This may play a major role in reducing
      the impact of a highly lethal disease when ecological conditions enable permanent
      circulation of the pathogen. 

PMID- 24589195
TI  - Early classification of childhood focal idiopathic epilepsies: is it possible at
      the first seizure?
AB  - PURPOSES: To evaluate the possibility of early syndrome classification of
      idiopathic partial epilepsies in children at the first seizure. PATIENTS AND
      METHODS: In this observational study we prospectively evaluated 298 patients,
      aged between 1 month and 17 years and consecutively referred for the first
      unprovoked focal seizure. The whole cohort included 133 patients; the final
      analysis was carried out on 107 (59 males) individuals. Age at the first seizure
      ranged between 2.3 and 13.0 years. Clinical and EEG data of all patients were
      independently reviewed by two medical doctors. Patients were followed-up for at
      least 5 years, with a mean period of follow-up of 6.9 years. RESULTS: After the
      first seizure, a specific syndrome could be diagnosed in eighty (74.7%) children.
      In particular, Childhood Epilepsy with Centro-Temporal Spikes (CECTS) 42.9% of
      cases, Panayiotopoulos Syndrome (PS) 28.9%, idiopathic childhood occipital
      epilepsy of Gastaut (ICOE-G) 2.8%. Unclassified cases were 25.4%. At the end of
      the follow-up, the diagnosis was confirmed in 72 of 80 children (90%): BCECTS 89%
      of patients, PS 90% and ICOE-G 100%: among the unclassified cases, in 11 patients
      (40.7%) the diagnosis did not change, whereas 16 patients (59.3%) evolved into
      other syndromes or into atypical forms. CONCLUSIONS: At the onset an initial
      diagnosis is possible in the majority of cases; epilepsy syndromes can be
      identified at the time of the initial diagnosis and at follow up this diagnosis
      has not to be revised in 90% of the cases.

PMID- 24589194
TI  - Are the ACC/AHA guidelines on the treatment of blood cholesterol a game changer?
      A perspective from the Canadian Cardiovascular Society Dyslipidemia Panel.

PMID- 24589197
TI  - The impact of CHIP premium increases on insurance outcomes among CHIP eligible
      children.
AB  - BACKGROUND: Within the United States, public insurance premiums are used both to
      discourage private health policy holders from dropping coverage and to reduce
      state budget costs. Prior research suggests that the odds of having private
      coverage and being uninsured increase with increases in public insurance
      premiums. The aim of this paper is to test effects of Children's Health Insurance
      Program (CHIP) premium increases on public insurance, private insurance, and
      uninsurance rates. METHODS: The fact that families just below and above a state
      specific income cut-off are likely very similar in terms of observable and
      unobservable characteristics except the premium contribution provides a natural
      experiment for estimating the effect of premium increases. Using 2003 Medical
      Expenditure Panel Survey (MEPS) merged with CHIP premiums, we compare health
      insurance outcomes for CHIP eligible children as of January 2003 in states with a
      two-tier premium structure using a cross-sectional regression discontinuity
      methodology. We use difference-in-differences analysis to compare longitudinal
      insurance outcomes by December 2003. RESULTS: Higher CHIP premiums are associated
      with higher likelihood of private insurance. Disenrollment from CHIP in response
      to premium increases over time does not increase the uninsurance rate.
      CONCLUSIONS: When faced with higher CHIP premiums, private health insurance may
      be a preferable alternative for CHIP eligible families with higher incomes.
      Therefore, competition in the insurance exchanges being formed under the
      Affordable Care Act could enhance choice.

PMID- 24589198
TI  - Predictors for improvement of problem-solving during cognitive remediation for
      patients with Schizophrenia.
AB  - Cognitive remediation is a promising pathway for ameliorating cognitive
      impairment of patients with schizophrenia. Here, we investigate predictors of
      improvement in problem-solving ability for two different types of cognitive
      remediation - specific problem-solving training and training of basic cognition.
      For this purpose we conducted a re-analysis of a randomized controlled trial
      comparing these two training approaches. The main outcome measure was improvement
      in problem-solving performance. Correlational analyses were used to assess the
      contribution of clinical, cognitive and training-related predictors. In the
      problem-solving training group, impaired pre-training planning ability was
      associated with stronger improvement. In contrast, in the basic cognition
      training group antipsychotic medication dose emerged as a negative predictor.
      These results demonstrate that predictors for successful cognitive remediation
      depend on the specific intervention. Furthermore, our results suggest that at
      least in the planning domain patients with impaired performance benefit
      particularly from a specific intervention.

PMID- 24589199
TI  - Mitral valve surgery: right lateral minithoracotomy or sternotomy? A systematic
      review and meta-analysis.
AB  - OBJECTIVE: To update the current evidence on mitral valve surgery through a
      lateral minithoracotomy versus median sternotomy. METHODS: A comprehensive
      literature research was performed for studies comparing mitral valve surgery
      through a right lateral minithoracotomy (MIVS) and median sternotomy in MEDLINE,
      EMBASE, Cochrane Central, CTSnet, and Google Scholar for the most recent
      literature up to April 2013. A systematic review and meta-analysis was performed
      on the studies found in the literature. RESULTS: More than 20,000 patients from
      45 studies were included in this study. Stroke rate and all-cause mortality up to
      30 days was similar in both groups. The length of stay in the intensive care
      unit, respirator dependence, and hospital stay were significantly shorter in the
      MIVS group. Furthermore, blood drainage volume and blood transfusions were
      decreased in the MIVS group. In contrast, cardiopulmonary bypass time, crossclamp
      time, and procedure time were longer in the MIVS group. Postoperative new atrial
      fibrillation was less in the MIVS group. More aortic dissections occurred in the
      MIVS group. The rates of reexploration and postoperative renal failure were
      similar in both groups. CONCLUSIONS: MIVS and conventional mitral valve surgery
      have a similar perioperative outcome. Mitral valve surgery via a right lateral
      minithoracotomy seems to be favorable with regard to resource-related outcome.

PMID- 24589200
TI  - Timing of valve repair for severe degenerative mitral regurgitation and long-term
      left ventricular function.
AB  - OBJECTIVES: Current guidelines recommended surgery for patients with severe
      degenerative mitral regurgitation (MR) when specific left ventricular (LV)
      dimensions or ejection fraction (EF) are reached, based on previous postoperative
      survival studies. The aim of this study was to evaluate the incidence and
      predictors of long-term postoperative LV dysfunction, and investigate the
      preoperative parameters necessary to maintain or recover long-term LV function in
      the era of mitral valve (MV) repair. METHODS: We retrospectively reviewed 473
      consecutive patients undergoing MV repair for severe degenerative MR for whom
      both preoperative and 3-year postoperative echocardiographic data were available
      in our institution. Preoperative and 3-year postoperative echocardiographic data
      and clinical outcomes were evaluated. RESULTS: Receiver operating characteristic
      analysis identified preoperative LVEF 63% or less (area under curve [AUC], 0.725;
      P<.001) and LV end-systolic dimension (ESD) 39 mm or greater (AUC, 0.724; P<.001)
      as cut-off values for predicting LVEF less than 50% 3 years after surgery. On
      multivariate analysis, both preoperative LVEF and LVESD were not significant
      predictors of 3-year postoperative LV dysfunction among patients with
      preoperative LVEF greater than 63% and LVESD less 39 mm, whereas preoperative
      LVESD (odds ratio [OR], 2.22; P=.004), higher age (OR, 1.03; P=.04), and atrial
      fibrillation (OR, 2.68; P=.01) were independent predictors among patients with
      preoperative LVEF 63% or less or LVESD 39 mm or greater. CONCLUSIONS: Early MV
      repair with LVEF greater than 63% and LVESD less than 39 mm preserved long-term
      postoperative LV function well, and smaller preoperative LVESD was associated
      with long-term LV function recovery, even in patients with preoperative LV
      dysfunction.

PMID- 24589201
TI  - Mitral valve repair versus replacement in the elderly: short-term and long-term
      outcomes.
AB  - OBJECTIVE: To compare the short-term and long-term outcomes of mitral valve
      repair (MVP) versus mitral valve replacement (MVR) in elderly patients. METHODS:
      All patients, age 70 years or greater, with mitral regurgitation who underwent
      MVP or MVR with or without coronary artery bypass graft (CABG), tricuspid valve
      surgery, or a maze procedure between 2002 and 2011 were retrospectively
      identified. Patients with a rheumatic cause or who underwent concomitant aortic
      valve or ventricular-assist device procedures were excluded. RESULTS: Overall,
      556 patients underwent MVP and 102 patients underwent MVR. The mean age of the
      patients in the MVR group was 78 years versus 77 years for those in the MVP group
      (P<.02). The patients in the MVR group had a better mean left ventricular
      ejection fraction than those in the MVP group (60% vs 55%, P=.04). The incidence
      of concomitant CABG, tricuspid valve operations, and atrial fibrillation ablation
      procedures was similar in both groups, but perfusion time was significantly
      longer for the MVR group (median 177 minutes vs 146 minutes for MVP, P=.001).
      Postoperatively, patients in the MVR group had a higher incidence of stroke (6%
      vs 2%, P<.10) and significantly longer intensive care unit stay (median 86 hours
      vs 55 hours, P=.001) and hospital stay (9 days vs 8 days, P<.01). Operative
      mortality of patients was significantly higher for the MVR group (8.8% vs 3.6%,
      P=.03) and remained significant long-term on Kaplan-Meier analysis. Cox
      regression analysis of all 658 patients and propensity-matched analysis of 96
      patients also confirmed these results. CONCLUSIONS: Elderly patients with mitral
      regurgitation who undergo MVP have better postoperative outcomes, lower operative
      mortality, and improved long-term survival than those undergoing MVR. MVP is a
      safe and more effective option for the elderly with mitral regurgitation.

PMID- 24589202
TI  - Outcomes in lung transplantation after previous lung volume reduction surgery in
      a contemporary cohort.
AB  - OBJECTIVES: Lung volume reduction surgery (LVRS) provides palliation and improved
      quality of life in select patients with end-stage chronic obstructive pulmonary
      disease (COPD). The effect of previous LVRS on lung transplant outcomes has been
      inadequately studied. We report our experience in the largest single institution
      series of these combined procedures. METHODS: The records of 472 patients with
      COPD undergoing lung transplantation or LVRS between 1995 and 2010 were reviewed.
      Outcomes of patients undergoing transplant after LVRS were compared with outcomes
      of patients undergoing transplant or LVRS alone. Survival was compared using log
      rank tests and the Kaplan-Meier method. RESULTS: Demographics, comorbidities, and
      spirometry were similar at the time of transplantation. Patients who had
      undergone lung transplant after LVRS had longer transplant operative times (mean
      4.4 vs 5.6 hours; P = .020) and greater hospital length of stay (mean 17.6 vs
      29.1 days; P = .005). Thirty-day mortality and major morbidity were similar.
      Posttransplant survival was reduced for transplant after LVRS (median, 49 months;
      95% confidence interval [CI], 16, 85 months) compared with transplant alone
      (median, 96 months; 95% CI, 82, 106 months; P = .008). The composite benefit of
      combined procedures, defined as bridge from LVRS to transplant of 55 months and
      posttransplant survival of 49 months (total 104 months), was comparable with
      survival of patients undergoing either procedure alone. CONCLUSIONS: Lung
      transplant after LVRS leads to minimal additional perioperative risk. The reduced
      posttransplant survival in patients undergoing combined procedures is in
      contradistinction to reports from other smaller series. When determining the best
      surgical treatment for patients with more severe disease, the benefit of LVRS
      before transplant should be weighed against the consequence of reduced
      posttransplant survival.

PMID- 24589203
TI  - Thermodynamic characterization of proton-ionizable functional groups on the cell
      surfaces of ammonia-oxidizing bacteria and archaea.
AB  - The ammonia-oxidizing archaeon Nitrosopumilus maritimus strain SCM1 (strain
      SCM1), a representative of the Thaumarchaeota archaeal phylum, can sustain high
      specific rates of ammonia oxidation at ammonia concentrations too low to sustain
      metabolism by ammonia-oxidizing bacteria (AOB). One structural and biochemical
      difference between N. maritimus and AOB that might be related to the oligotrophic
      adaptation of strain SCM1 is the cell surface. A proteinaceous surface layer (S
      layer) comprises the outermost boundary of the strain SCM1 cell envelope, as
      opposed to the lipopolysaccharide coat of Gram-negative AOB. In this work, we
      compared the surface reactivities of two archaea having an S-layer (strain SCM1
      and Sulfolobus acidocaldarius) with those of four representative AOB
      (Nitrosospira briensis, Nitrosomonas europaea, Nitrosolobus multiformis, and
      Nitrosococcus oceani) using potentiometric and calorimetric titrations to
      evaluate differences in proton-ionizable surface sites. Strain SCM1 and S.
      acidocaldarius have a wider range of proton buffering (approximately pH 10-3.5)
      than the AOB (approximately pH 10-4), under the conditions investigated.
      Thermodynamic parameters describing proton-ionizable sites (acidity constants,
      enthalpies, and entropies of protonation) are consistent with these archaea
      having proton-ionizable amino acid side chains containing carboxyl, imidazole,
      thiol, hydroxyl, and amine functional groups. Phosphorous-bearing acidic
      functional groups, which might also be present, could be masked by imidazole and
      thiol functional groups. Parameters for the AOB are consistent with surface
      structures containing anionic oxygen ligands (carboxyl- and phosphorous-bearing
      acidic functional groups), thiols, and amines. In addition, our results showed
      that strain SCM1 has more reactive surface sites than the AOB and a high
      concentration of sites consistent with aspartic and/or glutamic acid. Because
      these alternative boundary layers mediate interaction with the local external
      environment, these data provide the basis for further comparisons of the
      thermodynamic behavior of surface reactivity toward essential nutrients. 

PMID- 24589204
TI  - Transarterial chemoembolisation and radioembolisation for the treatment of
      primary liver cancer and secondary liver cancer: a review of the literature.
AB  - Liver-directed therapies are continuing to evolve in the field of interventional
      oncology and are gaining increasing use in the treatment of unresectable primary
      and secondary liver cancers. In this article, we review two liver-directed
      therapies that are currently used for the palliative treatment of primary and
      secondary hepatic tumours: transcatheter arterial chemoembolisation (TACE),
      including a new type of TACE with drug-eluting beads (DEB-TACE), and
      radioembolisation. The concept of these transcatheter intraarterial therapies is
      to selectively deliver high doses of anticancer treatment to the tumour. While
      TACE delivers one or more chemotherapeutic drugs into the hepatic arteries
      supplying the tumour, radioembolisation uses non-embolic microspheres
      incorporating the radioactive isotope (90) Y. In this article, we discuss some
      technical aspects, patient selection, current clinical evidence, and future
      directions of TACE, TACE with drug-eluting beads (DEB-TACE) and radioembolisation
      for primary and secondary liver cancer. 

PMID- 24589205
TI  - Assessing a commercially available sports drink on exogenous carbohydrate
      oxidation, fluid delivery and sustained exercise performance.
AB  - BACKGROUND: Whilst exogenous carbohydrate oxidation (CHOEXO) is influenced by
      mono- and disaccharide combinations, debate exists whether such beverages enhance
      fluid delivery and exercise performance. Therefore, this study aimed to ascertain
      CHOEXO, fluid delivery and performance times of a commercially available
      maltodextrin/ fructose beverage in comparison to an isocaloric maltodextrin
      beverage and placebo. METHODS: Fourteen club level cyclists (age: 31.79 +/- 10.02
      years; height: 1.79 +/- 0.06 m; weight: 73.69 +/- 9.24 kg; VO2max: 60.38 +/- 9.36
      mL . kg.-1 min-1) performed three trials involving 2.5 hours continuous exercise
      at 50% maximum power output (Wmax: 176.71 +/- 25.92 W) followed by a 60 km
      cycling performance test. Throughout each trial, athletes were randomly assigned,
      in a double-blind manner, either: (1) 1.1 g . min-1 maltodextrin + 0.6 g . min-1
      fructose (MD + F), (2) 1.7 g . min-1 of maltodextrin (MD) or (3) flavoured water
      (P). In addition, the test beverage at 60 minutes contained 5.0 g of deuterium
      oxide (2H2O) to assess quantification of fluid delivery. Expired air samples were
      analysed for CHOEXO according to the 13C/12C ratio method using gas
      chromatography continuous flow isotope ratio mass spectrometry. RESULTS: Peak
      CHOEXO was significantly greater in the final 30 minutes of submaximal exercise
      with MD + F and MD compared to P (1.45 +/- 0.09 g . min-1, 1.07 +/- 0.03 g . min
      1and 0.00 +/- 0.01 g . min-1 respectively, P < 0.0001), and significantly greater
      for MD + F compared to MD (P = 0.005). The overall appearance of 2H2O in plasma
      was significantly greater in both P and MD + F compared to MD (100.27 +/- 3.57
      ppm, 92.57 +/- 2.94 ppm and 78.18 +/- 4.07 ppm respectively, P < 0.003). There
      was no significant difference in fluid delivery between P and MD + F (P = 0.078).
      Performance times significantly improved with MD + F compared with both MD (by 7
      min 22 s +/- 1 min 56 s, or 7.2%) and P (by 6 min 35 s +/- 2 min 33 s, or 6.5%, P
      < 0.05) over 60 km. CONCLUSIONS: A commercially available maltodextrin-fructose
      beverage improves CHOEXO and fluid delivery, which may benefit individuals during
      sustained moderate intensity exercise. The greater CHOEXO observed when consuming
      a maltodextrin-fructose beverage may support improved performance times.

PMID- 24589206
TI  - Using Bourdieu's theory of practice to understand ICT use amongst nurse
      educators.
AB  - BACKGROUND: Implementing changes in practice in either clinical or educational
      settings remains challenging. In the context of Information and Communication
      Technologies (ICT) adoption, the literature focuses either on organisational
      factors influencing its implementation, or on individual factors influencing its
      adoption into practice. Separately both fail to examine the issue holistically.
      Bourdieu's theory of practice provides a method for reconciling the two.
      OBJECTIVE: To provide a practical example of how Bourdieu's theory of practice
      can be employed to better understand nurse educators' responses to ICT. DESIGN:
      Exploratory descriptive design, using a Bourdieusian case-study to guide a
      documentary analysis. METHODS: In 2009 a two-part study was conducted within a
      Department of Nursing (DON) in higher education (HE) in England. First Bourdieu's
      theory of practice was used to develop a case-study; then nurse educators were
      recruited for a Q-methodology (Q) study. This paper focuses exclusively on the
      case study and the use of the theory of practice to interpret the findings from
      the Q-study. RESULTS: Nursing's transition into academia, promotions criteria in
      HE and the value placed on research over teaching have influenced educators'
      responses to technology. CONCLUSION: The use of Bourdieu's framework provides a
      rich and contextual backdrop for understanding how organisational factors
      interact to influence individuals' responses to technology adoption.

PMID- 24589207
TI  - Health behaviour models and patient preferences regarding nutrition and physical
      activity after breast or prostate cancer diagnosis.
AB  - This study aimed to improve understanding of prostate and breast cancer
      survivors' physical activity and nutrition and the association of these
      behaviours with two models. The first model, the Commonsense Self-Regulation
      Model (CSM), addresses cognitive and emotional perceptions of illness whereas the
      Transtheoretical Model (TTM) focuses on stage of readiness to engage in a
      behaviour. Participants who had been diagnosed with either breast (n = 145) or
      prostate cancer (n = 92) completed measures of demographic and health
      information, illness representations, stage of change, self-efficacy and
      preferences regarding health behaviour interventions. Health behaviours in the
      past seven days were measured via the International Physical Activity
      Questionnaire and concordance with national dietary guidelines. As hypothesised,
      TTM variables (stage of change and self-efficacy) demonstrated independent
      associations with physical activity and nutrition in regression analyses. CSM
      variables were not independently associated with absolute levels of health
      behaviours but both TTM and CSM variables were independently associated with self
      reported changes in physical activity and nutrition following prostate or breast
      cancer diagnosis. Many participants reported high interest in receiving lifestyle
      interventions, particularly soon after diagnosis. Results supported application
      of the TTM and CSM models for strengthening behaviour change intentions and
      actions in breast and prostate cancer survivors. 

PMID- 24589208
TI  - Collision tumor of the kidney composed of clear cell carcinoma and collecting
      duct carcinoma: report of a case with unusual morphology and clinical follow-up.
AB  - We report the case of a 67-year-old female who presented with a large renal mass.
      Gross examination of the nephrectomy specimen demonstrated a 6-cm renal mass that
      invaded into the renal sinus and perinephric fat. Histologic examination revealed
      two distinct tumor types. The first type was a conventional (clear cell) renal
      cell carcinoma that was of low nuclear grade and comprised the minority of the
      overall tumor. The second type was a high-grade collecting duct carcinoma with
      glandular/tubular differentiation and composed the majority of the tumor.
      Immunohistochemical studies demonstrated distinctive patterns of the two tumor
      types, thus confirming two distinct lineages. Five months postoperatively, the
      patient developed metastasis to the lungs and right hilar lymph node region. A
      fine needle aspiration of a lung nodule demonstrated a metastatic, poorly
      differentiated carcinoma, similar to the collecting duct carcinoma component in
      the kidney. Collision tumors of the kidney are rare with fewer than 10 cases
      reported in the literature. Our report further expands the spectrum of this rare
      phenomenon. 

PMID- 24589209
TI  - Colorectal cancer: new developments after the 2013 ECCO/ESMO congress.
AB  - In 2013, at the congress of the European CanCer Organization and the European
      Society for Medical Oncology, colorectal cancer was the subject of various oral
      presentations and posters. In this article, we have selected the most innovative
      studies that are likely to change our daily practice. 

PMID- 24589210
TI  - Mini-invasive surgery for colorectal cancer.
AB  - Laparoscopic techniques have been extensively used for the surgical management of
      colorectal cancer during the last two decades. Accumulating data have
      demonstrated that laparoscopic colectomy is associated with better short-term
      outcomes and equivalent oncologic outcomes when compared with open surgery.
      However, some controversies regarding the oncologic quality of mini-invasive
      surgery for rectal cancer exist. Meanwhile, some progresses in colorectal
      surgery, such as robotic technology, single-incision laparoscopic surgery,
      natural orifice specimen extraction, and natural orifice transluminal endoscopic
      surgery, have been made in recent years. In this article, we review the published
      data and mainly focus on the current status and latest advances of mini-invasive
      surgery for colorectal cancer. 

PMID- 24589212
TI  - Magnitude of income-related disparities in adverse perinatal outcomes.
AB  - BACKGROUND: To assess and compare multiple measurements of socioeconomic position
      (SEP) in order to determine the relationship with adverse perinatal outcomes
      across various contexts. METHODS: A birth registry, the Nova Scotia Atlee
      Perinatal Database, was confidentially linked to income tax and related
      information for the year in which delivery occurred. Multiple logistic regression
      was used to examine odds ratios between multiple indicators of SEP and multiple
      adverse perinatal outcomes in 117734 singleton births between 1988 and 2003.
      Models for after tax family income were also adjusted for neighborhood
      deprivation to gauge the relative magnitude of effects related to SEP at both
      levels. Effects of SEP were stratified by single- versus multiple-parent family
      composition, and by urban versus rural location of residence. RESULTS: The risk
      of small for gestational age and spontaneous preterm birth was higher across all
      the indicators of lower SEP, while risk for large for gestational age was lower
      across indicators of lower SEP. Higher risk of postneonatal death was
      demonstrated for several measures of lower SEP. Higher material deprivation in
      the neighborhood of residence was associated with increased risk for perinatal
      death, small for gestational age birth, and iatrogenic and spontaneous preterm
      birth. Family composition and urbanicity were shown to modify the association
      between income and some perinatal outcomes. CONCLUSIONS: This study highlights
      the importance of understanding the definitions of SEP and the mechanisms that
      lead to the association between income and poor perinatal outcomes, and
      broadening the types of SEP measures used in some cases.

PMID- 24589211
TI  - MicroRNA-mRNA functional pairs for cisplatin resistance in ovarian cancer cells.
AB  - Ovarian cancer is the leading cause of death in women worldwide. Cisplatin is the
      core of first-line chemotherapy for patients with advanced ovarian cancer. Many
      patients eventually become resistant to cisplatin, diminishing its therapeutic
      effect. MicroRNAs (miRNAs) have critical functions in diverse biological
      processes. Using miRNA profiling and polymerase chain reaction validation, we
      identified a panel of differentially expressed miRNAs and their potential targets
      in cisplatin-resistant SKOV3/DDP ovarian cancer cells relative to cisplatin
      sensitive SKOV3 parental cells. More specifically, our results revealed
      significant changes in the expression of 13 of 663 miRNAs analyzed, including 11
      that were up-regulated and 2 that were down-regulated in SKOV3/DDP cells with or
      without cisplatin treatment compared with SKOV3 cells with or without cisplatin
      treatment. miRNA array and mRNA array data were further analyzed using Ingenuity
      Pathway Analysis software. Bioinformatics analysis suggests that the genes
      ANKRD17, SMC1A, SUMO1, GTF2H1, and TP73, which are involved in DNA damage
      signaling pathways, are potential targets of miRNAs in promoting cisplatin
      resistance. This study highlights candidate miRNA-mRNA interactions that may
      contribute to cisplatin resistance in ovarian cancer. 

PMID- 24589213
TI  - At-risk characteristics for hospital admissions and ED visits.
AB  - PURPOSE: The purpose of this study was to explore the factors associated with
      hospital utilization among infants and young children with complex chronic
      conditions (CCC). DESIGN AND METHODS: A descriptive, retrospective study was
      conducted with 216 medical records of children with CCC. RESULTS: Greater
      complexity, younger age, living with siblings, use of public insurance or self
      pay, use of more than one type of insurance, and presence of conditions affecting
      certain body systems were associated with increased hospital and emergency
      department (ED) utilization. PRACTICE IMPLICATIONS: Nurses must have a heightened
      awareness of these at-risk characteristics to prevent avoidable hospital
      admissions and ED visits.

PMID- 24589215
TI  - Commentary: Comparison of the prevalence of surgical site infection with use of
      sterile and nonsterile gloves for resection and reconstruction during Mohs
      surgery.

PMID- 24589216
TI  - Commentary: Does preoperative curettage predispose to floaters?

PMID- 24589214
TI  - Neotrombicula inopinata (Acari: Trombiculidae) - a possible causative agent of
      trombiculiasis in Europe.
AB  - BACKGROUND: For over a decade, the presence of trombiculid mites in some mountain
      areas of La Rioja (Northern Spain) and their association with seasonal human
      dermatitis have been recognized. This work aimed to establish the species
      identity of the agent causing trombiculiasis in the study area. METHODS:
      Trombiculid larvae (chigger mites) were collected from vegetation in the Sierra
      Cebollera Natural Park and in Sierra La Hez during an outbreak of human
      trombiculiasis in 2010. Three specimens collected from a bird were also examined.
      Identification was made using morphological and morphometric traits based on the
      most recent taxonomic sources. A comparison of those mites with specimens of the
      same species collected throughout Europe was performed by means of cluster
      analysis with multiscale bootstrap resampling and calculation of approximately
      unbiased p-values. RESULTS: All collected mites were identified as Neotrombicula
      inopinata (Oudemans, 1909). Therefore, this species is the most likely causative
      agent of trombiculiasis in Spain, not Neotrombicula autumnalis (Shaw, 1790), as
      it was generally assumed. No chigger was identified as N. autumnalis in the study
      area. Neotrombicula inopinata clearly differs from N. autumnalis in the presence
      of eight or more setae in the 1st and 2nd rows of dorsal idiosomal setae vs. six
      setae in N. autumnalis. Comparison of N. inopinata samples from different
      locations shows significant geographic variability in morphometric traits.
      Samples from Western and Eastern Europe and the Caucasus formed three separate
      clusters. CONCLUSION: Since the taxonomical basis of many studies concerning N.
      autumnalis as a causative agent of trombiculiasis is insufficient, it is highly
      possible that N. inopinata may be hiding behind the common name of "harvest bug"
      in Europe, together with N. autumnalis.

PMID- 24589217
TI  - Passive immunization to reduce Campylobacter jejuni colonization and transmission
      in broiler chickens.
AB  - Campylobacter jejuni is the most common cause of bacterium-mediated diarrheal
      disease in humans worldwide. Poultry products are considered the most important
      source of C. jejuni infections in humans but to date no effective strategy exists
      to eradicate this zoonotic pathogen from poultry production. Here, the potential
      use of passive immunization to reduce Campylobacter colonization in broiler
      chicks was examined. For this purpose, laying hens were immunized with either a
      whole-cell lysate or the hydrophobic protein fraction of C. jejuni and their eggs
      were collected. In vitro tests validated the induction of specific
      ImmunoglobulinY (IgY) against C. jejuni in the immunized hens' egg yolks, in
      particular. In seeder experiments, preventive administration of hyperimmune egg
      yolk significantly (P < 0.01) reduced bacterial counts of seeder animals three
      days after oral inoculation with approximately 104 cfu C. jejuni, compared with
      control birds. Moreover, transmission to non-seeder birds was dramatically
      reduced (hydrophobic protein fraction) or even completely prevented (whole-cell
      lysate). Purified IgY promoted bacterial binding to chicken intestinal mucus,
      suggesting enhanced mucosal clearance in vivo. Western blot analysis in
      combination with mass spectrometry after two-dimensional gel-electrophoresis
      revealed immunodominant antigens of C. jejuni that are involved in a variety of
      cell functions, including chemotaxis and adhesion. Some of these (AtpA, EF-Tu,
      GroEL and CtpA) are highly conserved proteins and could be promising targets for
      the development of subunit vaccines. 

PMID- 24589218
TI  - Abnormality of the mandible ramus and a tumor in the parotid region.

PMID- 24589219
TI  - The assessment of the stability in mandibular setback surgery related to spatial
      factors under rotational control of the proximal segment.
AB  - OBJECTIVE: To evaluate the surgical relapse of mandibular setback, related to the
      magnitude of setback and LeFort I osteotomy under rotational control of the
      proximal segment. STUDY DESIGN: Data from 78 patients who had undergone sagittal
      split ramus osteotomy for mandibular prognathism were reviewed. The stability of
      the proximal segment was retrospectively confirmed. Serial cephalograms were used
      to assess relapse over 1 year. The association between relapse and LeFort I
      osteotomy as well as the magnitude of setback was assessed. RESULTS: Minimal
      counterclockwise rotation was noted postoperatively, but the proximal segment
      remained stable for 1 year. Notable forward relapse was shown in the setback of
      more than 7 mm (P < .01) with resumption of function after 6 weeks, but it was
      not related with LeFort I osteotomy. CONCLUSIONS: Relapse was related to the
      amount of setback and occurred on resumption of function despite rotational
      control of the proximal segment.

PMID- 24589220
TI  - Multiple natural enemies cause distance-dependent mortality at the seed-to
      seedling transition.
AB  - Specialised natural enemies maintain forest diversity by reducing tree survival
      in a density- or distance-dependent manner. Fungal pathogens, insects and mammals
      are the enemy types most commonly hypothesised to cause this phenomenon. Still,
      their relative importance remains largely unknown, as robust manipulative
      experiments have generally targeted a single enemy type and life history stage.
      Here, we use fungicide, insecticide and physical exclosure treatments to isolate
      the impacts of each enemy type on two life history stages (germination and early
      seedling survival) in three tropical tree species. Distance dependence was
      evident for five of six species-stage combinations, with each enemy type causing
      distance dependence for at least one species stage and their importance varying
      widely between species and stages. Rather than implicating one enemy type as the
      primary agent of this phenomenon, our field experiments suggest that multiple
      agents acting at different life stages collectively contribute to this diversity
      promoting mechanism. 

PMID- 24589221
TI  - Molecular characterization of a 4,409,480 bp deletion of the human X chromosome
      in a patient with haemophilia B.

PMID- 24589222
TI  - Weaker masturbatory erection may be a sign of early cardiovascular risk
      associated with erectile dysfunction in young men without sexual intercourse.
AB  - INTRODUCTION: Although increasing evidences emphasize the importance of early
      cardiovascular evaluation in men with erectile dysfunction (ED) of unexplained
      aetiology, impaired masturbation-induced erections in young men are usually
      overlooked and habitually presumed to be psychological origin. AIMS: To evaluate
      the young men presenting weaker masturbatory erection with no sexual intercourse
      (WME-NS) and verify if this cohort have early cardiovascular risks associated
      with ED. METHODS: Male subjects aged 18-40 years with WME-NS were screened by
      analyzing detailed sexual intercourse and masturbatory history. The age-matched
      ED and non-ED population were identified by using International Index of Erectile
      Function-5 (IIEF-5). All subjects with acute and/or chronic diseases (including
      diagnosed hypertension and diabetes) and long-term pharmacotherapy were excluded.
      Nocturnal penile tumescence and rigidity (NPTR), systemic vascular parameters and
      biochemical indicators related to metabolism were assessed. MAIN OUTCOME
      MEASURES: Comparison analysis and logistic regression analysis were conducted
      among WME-NS, ED and non-ED population. RESULTS: In total, 78 WME-NS cases (mean
      28.99 +/- 5.92 years), 179 ED cases (mean 30.69 +/- 5.21 years) and 43 non-ED
      cases (mean 28.65 +/- 4.30 years) were screened for analysis. Compared with non
      ED group, WME-NS group had higher prevalence of early ED risk factors including
      endothelial dysfunction, insulin resistance, high level of glycosylated serum
      protein and abnormal NPTR. Multivariable-adjusted logistic regression analysis
      showed endothelia dysfunction (odds ratio: 8.83 vs. 17.11, both P < 0.001) was
      the independent risk factor for both WME-NS and ED. CONCLUSIONS: Weaker
      masturbatory erection may be a sign of early cardiovascular risk associated with
      ED in young men without sexual intercourse. More studies are warranted to
      elucidate the clinical benefits by targeting these formulated strategies.

PMID- 24589223
TI  - Measuring and decomposing the inequality of maternal health services utilization
      in western rural China.
AB  - BACKGROUND: To measure socioeconomic inequalities in maternal health services in
      rural western China and to analyze the determinants' contributions of
      inequalities. STUDY DESIGN: a cross-sectional study. METHODS: The data utilized
      in this study were obtained from a cross-sectional study from 10 provinces in
      rural Western China in 2005. Wealth index of household socioeconomic status was
      developed by using principle component analysis. Concentration index,
      concentration curve and decomposition of the concentration index were employed to
      measure socioeconomic inequality in maternal health services utilization.
      RESULTS: For more than four times prenatal visits, the concentration index was
      0.0605 (95% CI: 0.0603, 0.0607). The concentration index of hospital delivery was
      0.0230 (95% CI: 0.0210, 0.0240) and the concentration index of more than 2 times
      postnatal visits was 0.0842 (95% CI: 0.0836, 0.0847). Han ethnicity woman,
      particularly in conjunction with high school education and rich wealth status,
      was the main contributor to inequality in maternal health services utilization.
      CONCLUSIONS: There is a strong pro-rich inequality of maternal health services in
      rural western China. This study suggests that an effective way to reduce the
      inequality is not only to narrow the gap of income between the rich and poor, but
      focus education on ethnic minority woman in rural remote areas.

PMID- 24589224
TI  - Catechin-capped gold nanoparticles: green synthesis, characterization, and
      catalytic activity toward 4-nitrophenol reduction.
AB  - An eco-friendly approach is described for the green synthesis of gold
      nanoparticles using catechin as a reducing and capping agent. The reaction
      occurred at room temperature within 1 h without the use of any external energy
      and an excellent yield (99%) was obtained, as determined by inductively coupled
      plasma mass spectrometry. Various shapes of gold nanoparticles with an estimated
      diameter of 16.6 nm were green-synthesized. Notably, the capping of freshly
      synthesized gold nanoparticles by catechin was clearly visualized with the aid of
      microscopic techniques, including high-resolution transmission electron
      microscopy, atomic force microscopy, and field emission scanning electron
      microscopy. Strong peaks in the X-ray diffraction pattern of the as-prepared gold
      nanoparticles confirmed their crystalline nature. The catalytic activity of the
      as-prepared gold nanoparticles was observed in the reduction of 4-nitrophenol to
      4-aminophenol in the presence of NaBH4. The results suggest that the newly
      prepared gold nanoparticles have potential uses in catalysis. 

PMID- 24589225
TI  - How do women's diets compare with the new Australian dietary guidelines?
AB  - OBJECTIVE: To compare women's diets with recommended intakes from the new
      Australian Dietary Guidelines (ADG 2013). DESIGN: Cross-sectional study using
      data from the Australian Longitudinal Study on Women's Health. Diet was assessed
      using a validated FFQ. SETTING: Two nationally representative age cohorts of
      Australian women. SUBJECTS: Women in the young cohort (born 1973-1978, aged 31-36
      years) and mid-age cohort (born 1946-1951, aged 50-55 years). Women (n 18 226)
      were categorised into three groups: 'young women' (n 5760), young 'pregnant
      women' at the time or who had given birth in the 12 months prior to the survey (n
      1999) and 'mid-age women' (n 10 467). RESULTS: Less than 2 % of women in all
      three groups attained the ADG 2013 recommendation of five daily servings of
      vegetables, with the majority needing more than two additional servings. For
      young women, less than one-third met recommendations for fruit (32%) and meat and
      alternatives (28 %), while only a small minority did so for dairy (12 %) and
      cereals (7 %). Fifty per cent of pregnant women met guidelines for fruit, but low
      percentages reached guidelines for dairy (22 %), meat and alternatives (10 %) and
      cereals (2.5 %). For mid-age women, adherence was higher for meat and
      alternatives (41 %) and cereals (45 %), whereas only 1 % had the suggested dairy
      intake of four daily servings. CONCLUSIONS: For most women to follow ADG 2013
      recommendations would require substantially increased consumption of cereals,
      vegetables and dairy. Findings have implications for tailoring the dissemination
      of dietary guidelines for women in different age groups and for pregnant women.

PMID- 24589226
TI  - Senescence-secreted factors activate Myc and sensitize pretransformed cells to
      TRAIL-induced apoptosis.
AB  - Senescent cells secrete a plethora of factors with potent paracrine signaling
      capacity. Strikingly, senescence, which acts as defense against cell
      transformation, exerts pro-tumorigenic activities through its secretome by
      promoting tumor-specific features, such as cellular proliferation, epithelial
      mesenchymal transition and invasiveness. Tumor necrosis factor-related apoptosis
      inducing ligand (TRAIL) has the unique activity of activating cell death
      exclusively in tumor cells. Given that the senescence-associated secretome (SAS)
      supports cell transformation, we asked whether SAS factor(s) would establish a
      program required for the acquisition of TRAIL sensitivity. We found that
      conditioned media from several types of senescent cells (CMS) efficiently
      sensitized pretransformed cells to TRAIL, while the same was not observed with
      normal or immortalized cells. Dynamic transcription profiling of CMS-exposed
      pretransformed cells indicated a paracrine autoregulatory loop of SAS factors and
      a dominant role of CMS-induced MYC. Sensitization to TRAIL coincided with and
      depended on MYC upregulation and massive changes in gene regulation. Senescent
      cell-induced MYC silenced its target gene CFLAR, encoding the apoptosis inhibitor
      FLIPL , thus leading to the acquisition of TRAIL sensitivity. Altogether, our
      results reveal that senescent cell-secreted factors exert a TRAIL-sensitizing
      effect on pretransformed cells by modulating the expression of MYC and CFLAR.
      Notably, CMS dose-dependent sensitization to TRAIL was observed with TRAIL
      insensitive cancer cells and confirmed in co-culture experiments. Dissection and
      characterization of TRAIL-sensitizing CMS factors and the associated signaling
      pathway(s) will not only provide a mechanistic insight into the acquisition of
      TRAIL sensitivity but may lead to novel concepts for apoptogenic therapies of
      premalignant and TRAIL-resistant tumors.

PMID- 24589228
TI  - Editorial: surviving critical illness: intensive care and beyond.

PMID- 24589227
TI  - Prevalence and spatial distribution of Theileria parva in cattle under crop
      livestock farming systems in Tororo District, Eastern Uganda.
AB  - BACKGROUND: Tick-borne diseases (TBDs) present a major economic burden to
      communities across East Africa. Farmers in East Africa must use acaracides to
      target ticks and prevent transmission of tick-borne diseases such as
      anaplasmosis, babesiosis, cowdriosis and theileriosis; the major causes of cattle
      mortality and morbidity. The costs of controlling East Coast Fever (ECF), caused
      by Theileria parva, in Uganda are significant and measures taken to control
      ticks, to be cost-effective, should take into account the burden of disease. The
      aim of the present work was to estimate the burden presented by T. parva and its
      spatial distribution in a crop-livestock production system in Eastern Uganda.
      METHODS: A cross sectional study was carried out to determine the prevalence and
      spatial distribution of T. parva in Tororo District, Uganda. Blood samples were
      taken from all cattle (n: 2,658) in 22 randomly selected villages across Tororo
      District from September to December 2011. Samples were analysed by PCR and T.
      parva prevalence and spatial distribution determined. RESULTS: The overall
      prevalence of T. parva was found to be 5.3%. Herd level prevalence ranged from 0%
      to 21% with majority of the infections located in the North, North-Eastern and
      South-Eastern parts of Tororo District. No statistically significant differences
      in risk of infection were found between age classes, sex and cattle breed.
      CONCLUSIONS: T. parva infection is widely distributed in Tororo District, Uganda.
      The prevalence and distribution of T. parva is most likely determined by spatial
      distribution of R. appendiculatus, restricted grazing of calves and preferential
      tick control targeting draft animals.

PMID- 24589229
TI  - Editorial: Failure to care: nursing in a state of liquid modernity?

PMID- 24589230
TI  - Commentary on Kelly J (2013) Editorial: Learning is still the real business of
      the University. Journal of Clinical Nursing 22, e3-e4.

PMID- 24589231
TI  - Medication administration errors made by nurses reflect the level of pharmacy
      administration and hospital information infrastructure.

PMID- 24589233
TI  - [Medication reconciliation in primary care after hospital discharge].
AB  - OBJECTIVES: The primary objective of this study was to determine if changes
      prescribed in the usual treatment of patients at discharge from the hospital were
      updated in their active treatment sheet when they came to the Primary Care
      clinic. The secondary objectives included, determining whether the drug average
      varies between the admission and discharge, as well as, identifying other factors
      related to the modification of treatment during hospital admission including,
      among others, patient age or the number of drugs previously indicated. Finally,
      the relationship between the Primary Care Unit to which the patient belonged and
      the probability that the medication was reconciled was also examined. MATERIAL
      AND METHODS: This is an observational cross-sectional study conducted in the
      Bidasoa Integrated Healthcare Organization. The study included every patient over
      65 years old with multiple medication (taking 5 or more drugs) belonging to this
      organization, and discharged from Bidasoa Hospital between 15th October and 11th
      November 2012. The information on hospital discharges during this period was sent
      from the hospital to those responsible for patient safety in the Primary Health
      Care Centers. Each patient clinical history was reviewed in order to confirm if a
      visit (at least once in the first two weeks after discharge) had been made to
      their Primary Care Unit, and whether there had been a change in their active
      treatment sheet. RESULTS: Two hundred sixty-one patients (n=261) were discharged
      from Bidasoa Hospital in the study period, and 80 met the inclusion criteria. The
      discharge report proposed a change in the active treatment in 39 of them (49%).
      Of these, 35 (90%) attended a Primary Care clinic, and the changes were included
      in their active treatment sheet in 24 patients, representing 68% of those who
      contacted Primary Care, and 61% of those who would have required changes.
      CONCLUSIONS: The results demonstrate the need to establish a reconciliation
      medication program for patients on multiple medications after hospital discharge.
      Moreover, further studies are needed to investigate what may be the reasons why
      the changes to active treatment sheets are not taking place for some patients,
      despite these having visited Primary Care after having been discharged from
      hospital.

PMID- 24589234
TI  - Myocardial tissue perfusion predicts the evolution of fragmented QRS in patients
      with ST-segment elevation myocardial infarction undergoing primary percutaneous
      coronary intervention.
AB  - BACKGROUND: Fragmented QRS complex (fQRS) is associated with worse outcomes in
      several cardiovascular conditions. However, alterations in fQRS in patients with
      ST elevation myocardial infarction (STEMI) who underwent primary percutaneous
      coronary intervention (PCI) and association of fQRS with myocardial blush grade
      (MBG) has not been investigated until now. In this study, we aimed to investigate
      the association of MBG after primary PCI with evolution of fQRS. METHODS: Our
      study consisted of 401 consecutive patients with STEMI who underwent primary PCI.
      Patients were categorized into two subgroups according to persistence or new
      onset of fQRS (Group 1) and absence or resolution of fQRS (Group 2) at 48 hours
      after primary PCI. The evolution of fQRS on pre- and post-PCI ECG and their
      relation with myocardial reperfusion parameters were investigated. RESULTS:
      Patients in group 1 showed older age, higher rate of smoking, lower HDL
      cholesterol, lower LVEF, higher angina-to-door time, higher TIMI frame count, and
      high rate of patients with MBG <3 compared to patients with group 2 (P < 0.05).
      In correlation analysis, LVEF showed positive correlation with MBG (r = 0.448, P
      < 0.001) and negative correlation with the number of leads with fQRS (r = -0.335,
      P < 0.001). In multivariate regression analysis, new-onset or persistance of fQRS
      after primary PCI is significantly associated with MBG <3, peak CK-MB level, pre
      PCI fQRS at anterior localization and smoking. CONCLUSION: Our findings showed
      that despite complete ST-segment resolution in all patients, fQRS is
      independently associated with impaired microvascular myocardial perfusion. So,
      fQRS, as a simple and easily available noninvasive marker, may be useful in
      stratification of high-risk patients with increased extent of infarcted
      myocardium who underwent primary PCI.

PMID- 24589235
TI  - Bartonella henselae and B. koehlerae DNA in birds.

PMID- 24589236
TI  - Peptide deformylase inhibitor actinonin reduces celastrol's HSP70 induction while
      synergizing proliferation inhibition in tumor cells.
AB  - BACKGROUND: Celastrol is a promising anti-tumor agent, yet it also elevates heat
      shock proteins (HSPs), especially HSP70, this effect believed to reduce its anti
      tumor effects. Concurrent use of siRNA to increase celastrol's anti-tumor effects
      through HSP70 interference has been reported, but because siRNA technology is
      difficult to clinically apply, an alternative way to curb unwanted HSP70
      elevation caused by celastrol treatment is worth exploring. METHODS: In this
      work, we explore three alternative strategies to control HSP70 elevation: (1)
      Searching for cancer cell types that show no HSP70 elevation in the presence of
      celastrol (thus recommending themselves as suitable targets); (2) Modifying HSP70
      inducing chemical groups, i.e.: the carboxyl group in celastrol; and (3) Using
      signaling molecule inhibitors to specifically block HSP70 elevation while
      protecting and/or enhancing anti-tumor effects. RESULTS: The first strategy was
      unsuccessful since celastrol treatment increased HSP70 in all 7 of the cancer
      cell types tested, this result related to HSF1 activation. The ubiquity of HSF1
      expression in different cancer cells might explain why celastrol has no cell-type
      limitation for HSP70 induction. The second strategy revealed that modification of
      celastrol's carboxyl group abolished its ability to elevate HSP70, but also
      abolished celastrol's tumor inhibition effects. In the third strategy, 11
      inhibitors for 10 signaling proteins reportedly related to celastrol action were
      tested, and five of these could reduce celastrol-caused HSP70 elevation. Among
      these, the peptide deformylase (PDF) inhibitor, actinonin, could synergize
      celastrol's proliferation inhibition. CONCLUSIONS: Concurrent use of the chemical
      agent actinonin could reduce celastrol's HSP70 elevation and also enhance
      proliferation inhibition by celastrol. This combination presents a novel
      alternative to siRNA technology and is worth further investigation for its
      potentially effective anti-tumor action.

PMID- 24589237
TI  - The self-estimation index of erectile function-no sexual intercourse (SIEF-NS): a
      multidimensional scale to assess erectile dysfunction in the absence of sexual
      intercourse.
AB  - INTRODUCTION: A new concept of Erectile Dysfunction with No Sexual Intercourse
      (ED-NS) is proposed to acknowledge the subpopulation of patients who are unable
      to achieve or sustain an erection in the absence of sexual intercourse. Since the
      commonly used ED diagnostic tool, International Index of Erectile Function
      Questionnaire is not able to adequately assess the erectile function (EF) in the
      absence of intercourse, the researchers developed a new 10-item questionnaire to
      better evaluate the EF in this special patient subpopulation: Self-Estimation
      Index of Erectile Function-No Sexual Intercourse (SIEF-NS). AIM: To validate the
      reliability, sensitivity and specificity of SIEF-NS. METHODS: The study was
      carried out in three phases. Phase one applied component analysis to 126 ED-NS
      patients to search for the primary factors and Cronbach's alpha standardized
      statistic values for SIEF-NS. Phase two applied discriminant analysis to
      participants' (212 ED-NS patients and 193 normal controls) scores on each
      question item, each factor and the overall 10-item questionnaire. Phase three
      investigated SIEF-NS's capability of evaluating treatment effect on 41 ED-NS
      patients. MAIN OUTCOME MEASURES: Reliability, sensitivity and specificity were
      defined and used to evaluate the performance of SIEF-NS. RESULTS: EF by autonomic
      response (factor 1) and EF with potential sexual partners (factor 2) are the two
      primary factors with eigenvalues greater than 1.0. High degree of internal
      consistency was observed for the two factors and the 10-item questionnaire
      (Cronbach's alpha values: 0.871 for 10 items, 0.84 for factor 1, and 0.823 for
      factor 2). SIEF-NS demonstrated adequate construct validity, high sensitivity
      (0.925) and specificity (0.829) to diagnose ED-NS. The EF scores of ED-NS
      patients post treatment showed significant improvement (P < 0.05). CONCLUSION:
      SIEF-NS can be used to identify ED-NS patients and detect treatment-related EF
      changes in ED-NS patients.

PMID- 24589238
TI  - 5-methoxyindole metabolites of L-tryptophan: control of COX-2 expression,
      inflammation and tumorigenesis.
AB  - Cyclooxygenase-2(COX-2) overexpression promotes inflammation and tumorigenesis.
      COX-2 expression in response to diverse stimuli is tightly controlled to avoid
      persistent overexpression. 5-methoxyindole metabolites of L-tryptophan represent
      a new class of compounds that control COX-2 expression at the transcriptional
      level. Two of the metabolites, the newly discovered 5-methoxytryptophan (5-MTP,
      also known as cytoguardin) and N-acetyl 5-methoxytryptamine (melatonin) are the
      focus of this review. 5-MTP is produced by mesenchymal cells such as fibroblasts
      via 5-hydroxytryptophan (5-HTP). It inhibits COX-2 transcriptional activation
      induced by diverse proinflammatory and mitogenic factors. Cancer cells are
      deficient in cytoguardin production which contributes to COX-2 overexpression.
      Fibroblast-generated 5-MTP is capable of restoring the control of COX-2
      overexpression in cancer cells. 5-MTP blocks cancer cell migration and invasion
      in vitro and inhibits tumor growth and cancer metastasis in a xenograft model.
      Melatonin possesses similar COX-2 suppressing and anti-cancer properties albeit
      at supra-pharmacological concentrations. By contrast, 5-hydroxyindole metabolites
      of L-tryptophan such as 5-hydroxytryptamine (serotonin), 5-hydroxytryptophol and
      other serotonin catabolites do not control COX-2 expression. 5-hydroxytryptophan
      inhibits COX-2 expression through conversion to 5-MTP. The physiological
      relevance of 5-MTP as an endogenous regulator of inflammation and cancer
      metastasis remains to be investigated. On the other hand, 5-methoxyindole
      metabolites of tryptophan are valuable lead compounds for development of new anti
      inflammatory drugs and cancer chemoprevention. 

PMID- 24589239
TI  - [Flow-controlled needle: a new device for performing unassisted nerve blocks].

PMID- 24589240
TI  - The ecometric properties of a measurement instrument for prospective risk
      analysis in hospital departments.
AB  - BACKGROUND: Safety management systems have been set up in healthcare institutions
      to reduce the number of adverse events. Safety management systems use a
      combination of activities, such as identifying and assessing safety risks in the
      organizational processes through retrospective and prospective risk assessments.
      A complementary method to already existing prospective risk analysis methods is
      Tripod, which measures latent risk factors in organizations through staff
      questionnaires. The purpose of this study is to investigate whether Tripod can be
      used as a method for prospective risk analysis in hospitals and whether it can
      assess differences in risk factors between hospital departments. METHODS: Tripod
      measures risk factors in five organizational domains: (1) Procedures, (2)
      Training, (3) Communication, (4) Incompatible Goals and (5) Organization. Each
      domain is covered by 15 items in the questionnaire. A total of thirteen
      departments from two hospitals participated in this study. All healthcare staff
      working in the participating departments were approached. The multilevel method
      ecometrics was used to evaluate the validity and reliability of Tripod.
      Ecometrics was needed to ensure that the differences between departments were
      attributable to differences in risk at the departmental level and not to
      differences between individual perceptions of the healthcare staff. RESULTS: A
      total of 626 healthcare staff completed the questionnaire, resulting in a
      response rate of 61.7%. Reliability coefficients were calculated for the
      individual level and department level. At the individual level, reliability
      coefficients ranged from 0.78 to 0.87, at the departmental level they ranged from
      0.55 to 0.73. Intraclass correlations at the departmental level ranged from 3.7%
      to 8.5%, which indicate sufficient clustering of answers within departments. At
      both levels the domains from the questionnaire were positively interrelated and
      all significant. CONCLUSIONS: The results of this study show that Tripod can be
      used as a method for prospective risk analysis in hospitals. Results of the
      questionnaire provide information about latent risk factors in hospital
      departments. However, this study also shows that there are indications that the
      method is not sensitive enough to detect differences between hospital
      departments. Therefore, it is important to be careful when interpreting
      differences in potential risks between departments when using Tripod.

PMID- 24589241
TI  - Utilization of psychotropic drugs prescribed to persons with and without HIV
      infection: a Danish nationwide population-based cohort study.
AB  - OBJECTIVES: The objective was to estimate the utilization of psychotropic drugs
      in HIV-infected individuals compared with that in the background population.
      METHODS: Using data obtained from the Danish HIV Cohort Study and the Danish
      National Prescription Registry, we analysed aggregated data on redeemed
      prescription of psychotropic drugs during 1995-2009. We primarily focused our
      analyses on HIV-infected individuals with no history of injecting drug use (IDU)
      or hepatitis C virus (HCV) infection. Drug utilization was expressed as defined
      daily doses per 1000 person-days (DDD/1000PD). The utilization rate ratio (URR)
      was calculated as utilization in the HIV-infected cohort compared with that in
      the comparison cohort. We estimated longitudinal trends in utilization and
      potential associations with HIV and exposure to highly active antiretroviral
      therapy (HAART), especially efavirenz. RESULTS: During 1995-2009, 54.5% of the
      HIV-infected cohort (3615 non-IDU/non-HCV-infected HIV-infected individuals) and
      29.2% of the comparison cohort (32 535 individuals) had at least one prescription
      of a psychotropic drug. HIV infection was associated with a URR of 1.13 for
      antipsychotics, 1.76 for anxiolytics, 4.42 for hypnotics and sedatives, and 2.28
      for antidepressants. Antidepressants were confined primarily to men who have sex
      with men (MSM). Older age, more recent calendar time, and increased time after
      HIV diagnosis were associated with increased drug utilization. However, no
      association with exposure to HAART or efavirenz was found. CONCLUSIONS: HIV
      infected individuals had a higher utilization of psychotropic drugs than the
      background population, which was not confined to individuals with a history of
      IDU or HCV infection. This emphasizes the need to focus on diagnosis of, and
      appropriate psychopharmacological interventions for, mental disorders in this
      population.

PMID- 24589243
TI  - Development of an aptamer-conjugated fluorescent nanoprobe for MMP2.
AB  - Matrix metalloproteinase 2 (MMP2) plays critical roles in various diseases, such
      as atherosclerosis and cancer, and has been suggested to contribute to the
      instability of atherosclerotic plaque. To visualize MMP2 in pathologic tissues,
      we developed an aptamer targeting MMP2 protein by performing eight rounds of
      modified DNA systematic evolution of ligands by exponential enrichment (SELEX).
      The aptamer showed high affinity for MMP2 (Kd = 5.59 nM), precipitated MMP2, and
      detected MMP2 protein in pathological tissues such as atherosclerotic plaque and
      gastric cancer tissues. Furthermore, a MMP2 aptamer-conjugated fluorescent
      nanoprobe successfully visualized atherosclerotic plaques in apolipoprotein E
      (ApoE) knockout mice. These results suggest that the devised MMP2 aptamer could
      be useful for the development of various diagnostic tools. 

PMID- 24589242
TI  - Perioperative bromelain reduces pain and swelling and improves quality of life
      measures after mandibular third molar surgery: a randomized, double-blind,
      placebo-controlled clinical trial.
AB  - PURPOSE: The purpose of the present study was to compare the effect of oral
      bromelain (4 * 250 mg) versus oral diclofenac sodium (4 * 25 mg) on pain,
      swelling, trismus, and quality of life (QOL) after surgical removal of impacted
      lower third molars. PATIENTS AND METHODS: A randomized, double-blind, placebo
      controlled study was planned. The sample included patients requiring extraction
      under local anesthesia of a single partial bony impacted mandibular third molar.
      The patients were randomly distributed into 1 of 3 groups: bromelain, diclofenac,
      and placebo. Treatment started 1 day before surgery and continued for 4 days. The
      predictor variable was the type of the drug given to the patients. The outcome
      variables were pain, swelling, and trismus, which were measured at 1, 3, and 7
      days postoperatively. The other study variables included QOL measures to assess
      the patients' perception regarding the effect of surgery on their well-being and
      daily activities. A validated questionnaire was used to measure QOL. The data
      were analyzed using analysis of variance, multiple measures analysis of variance,
      or Pearson's chi(2) test, as appropriate. P < .05 was considered significant.
      RESULTS: A total of 45 subjects requiring surgical removal of a single impacted
      mandibular third molar under local anesthesia were included in the present study.
      The bromelain and diclofenac groups both showed a significant reduction in pain
      compared with the placebo group at all intervals (P < .05). Diclofenac also
      resulted in a significant reduction of swelling at 3 and 7 days, and bromelain
      resulted in an insignificant reduction. A nonsignificant reduction in trismus
      occurred in both treatment groups compared with the placebo group. Both treatment
      groups also showed a significant difference in the effect on QOL in most
      subscales and total scores (P < .05). The effect was comparable between the 2
      treatment groups for all parameters and at all intervals. CONCLUSIONS: The
      results of our study have shown that oral bromelain is an effective therapy to
      improve the QOL after surgical removal of impacted lower third molars, with an
      effect on the postoperative sequelae comparable to that of preemptive diclofenac
      sodium.

PMID- 24589244
TI  - The dynamics of assembling food webs.
AB  - Community assembly is central to ecology, yet ecologists have amassed little
      quantitative information about how food webs assemble. Theory holds that
      colonisation rate is a primary driver of community assembly. We present new data
      from a mesocosm experiment to test the hypothesis that colonisation rate also
      determines the assembly dynamics of food webs. By manipulating colonisation rate
      and measuring webs through time, we show how colonisation rate governs structural
      changes during assembly. Webs experiencing different colonisation rates had
      stable topologies despite significant species turnover, suggesting that some
      features of network architecture emerge early and change little through assembly.
      But webs experiencing low colonisation rates showed less variation in the
      magnitudes of trophic fluxes, and were less likely to develop coupled fast and
      slow resource channels--a common feature of published webs. Our results reveal
      that food web structure develops according to repeatable trajectories that are
      strongly influenced by colonisation rate.

PMID- 24589245
TI  - Shuttle walking test in obese women: test-retest reliability and concurrent
      validity with peak oxygen uptake.
AB  - OBJECTIVE: The aim of this study was to evaluate the test-retest reliability,
      concurrent validity and agreement with peak oxygen uptake (VO2 ) obtained during
      cardiopulmonary exercise testing (CPX) on a treadmill for the incremental shuttle
      walking test (ISWT) in obese women. METHODS: Prospective study with a convenient
      sample of 46 community-dwelling obese women (BMI > 30 kg m(-2) ). The main
      outcome measures were walking distance on the ISWT and peak VO2 . RESULTS: Test
      retest reliability was good to excellent for the exercise tests (ISWT distance
      ICC: 0.90; and CPX peak VO2 ICC: 0.90). Peak VO2 obtained during CPX correlated
      significantly with ISWT distance (r = 0.54, P<0.05) and peak VO2 obtained during
      the ISWT (r = 0.64, P<0.05). Bland and Altman plots demonstrated a high degree of
      repeatability. CONCLUSION: The ISWT had excellent reliability as well as good
      concurrent validity and agreement. The ISWT may be a potential tool for
      monitoring clinical status and intervention efficacy (e.g. programmes for weight
      loss and rehabilitative strategies) in this population.

PMID- 24589246
TI  - Determining the causal relationships among balanced scorecard perspectives on
      school safety performance: case of Saudi Arabia.
AB  - In the public schools of many developing countries, numerous accidents and
      incidents occur because of poor safety regulations and management systems. To
      improve the educational environment in Saudi Arabia, the Ministry of Education
      seeks novel approaches to measure school safety performance in order to decrease
      incidents and accidents. The main objective of this research was to develop a
      systematic approach for measuring Saudi school safety performance using the
      balanced scorecard framework philosophy. The evolved third generation balanced
      scorecard framework is considered to be a suitable and robust framework that
      captures the system-wide leading and lagging indicators of business performance.
      The balanced scorecard architecture is ideal for adaptation to complex areas such
      as safety management where a holistic system evaluation is more effective than
      traditional compartmentalised approaches. In developing the safety performance
      balanced scorecard for Saudi schools, the conceptual framework was first
      developed and peer-reviewed by eighteen Saudi education experts. Next, 200
      participants, including teachers, school executives, and Ministry of Education
      officers, were recruited to rate both the importance and the performance of 79
      measurement items used in the framework. Exploratory factor analysis, followed by
      the confirmatory partial least squares method, was then conducted in order to
      operationalise the safety performance balanced scorecard, which encapsulates the
      following five salient perspectives: safety management and leadership; safety
      learning and training; safety policy, procedures and processes; workforce safety
      culture; and safety performance. Partial least squares based structural equation
      modelling was then conducted to reveal five significant relationships between
      perspectives, namely, safety management and leadership had a significant effect
      on safety learning and training and safety policy, procedures and processes, both
      safety learning and training and safety policy, procedures and processes had
      significant effects on workforce safety culture, and workforce safety culture had
      a significant effect on safety performance.

PMID- 24589248
TI  - Hydrogen sulfide accelerates cell cycle progression in oral squamous cell
      carcinoma cell lines.
AB  - OBJECTIVE: To investigate the cell cycle regulator role of the third gaseous
      transmitter hydrogen sulfide (H2 S) in three oral SCC cell lines by using NaHS, a
      donor of H2 S. METHODS: The synchronized oral squamous cell carcinoma cell lines
      (Cal27, GNM, and WSU-HN6) were treated with different concentrations of NaHS and
      then subjected to cell proliferation, cell cycle, and Western blot analyses.
      RESULTS: The CCK-8 assay results showed that the exogenously administered H2 S
      donor, NaHS, induced CAL-27, and GNM cell proliferation in a concentration
      dependent manner, and the cell cycle analysis indicated that NaHS accelerated
      cell cycle progression of the synchronized CAL-27, GNM, and WSU-HN6 cells.
      Western blot analysis revealed that the cell cycle regulatory genes RPA70 and RB1
      were significantly down-regulated and that proliferating cell nuclear antigen
      (PCNA) and CDK4 were markedly up-regulated by NaHS at specific time points in the
      cell cycle. In addition, our results indicated that the phosphorylation of Akt
      and Erk1/2 was involved in exogenous H2 S-induced oral SCC cell proliferation.
      CONCLUSIONS: H2 S is a potential pro-proliferative factor of human oral SCC cells
      that accelerates the progression of the SCC cell cycle; thus, H2 S plays a
      deleterious role in oral SCC cancer development.

PMID- 24589247
TI  - Insecticide resistance of Anopheles sinensis and An. vagus in Hainan Island, a
      malaria-endemic area of China.
AB  - BACKGROUND: Malaria is one of the most important public health problems in
      Southeast Asia, including Hainan Island, China. Vector control is the main
      malaria control measure, and insecticide resistance is a major concern for the
      effectiveness of chemical insecticide control programs. The objective of this
      study is to determine the resistance status of the main malaria vector species to
      pyrethroids and other insecticides recommended by the World Health Organization
      (WHO) for indoor residual sprays. METHODS: The larvae and pupae of Anopheles
      mosquitoes were sampled from multiple sites in Hainan Island, and five sites
      yielded sufficient mosquitoes for insecticide susceptibility bioassays. Bioassays
      of female adult mosquitoes three days after emergence were conducted in the two
      most abundant species, Anopheles sinensis and An. vagus, using three insecticides
      (0.05% deltamethrin, 4% DDT, and 5% malathion) and following the WHO standard
      tube assay procedure. P450 monooxygenase, glutathione S-transferase and
      carboxylesterase activities were measured. Mutations at the knockdown resistance
      (kdr) gene and the ace-1 gene were detected by DNA sequencing and PCR-RFLP
      analysis, respectively. RESULTS: An. sinensis and An. vagus were the predominant
      Anopheles mosquito species. An. sinensis was found to be resistant to DDT and
      deltamethrin. An. vagus was susceptible to deltamethrin but resistant to DDT and
      malathion. Low kdr mutation (L1014F) frequency (<10%) was detected in An.
      sinensis, but no kdr mutation was detected in An. vagus populations. Modest to
      high (45%-75%) ace-1 mutation frequency was found in An. sinensis populations,
      but no ace-1 mutation was detected in An. vagus populations. Significantly higher
      P450 monooxygenase and carboxylesterase activities were detected in deltamethrin
      resistant An. sinensis, and significantly higher P450 monooxygenase, glutathione
      S-transferase and carboxylesterase activities were found in malathion-resistant
      An. vagus mosquitoes. CONCLUSIONS: Multiple insecticide resistance was found in
      An. sinensis and An. vagus in Hainan Island, a malaria-endemic area of China.
      Cost-effective integrated vector control programs that go beyond synthetic
      insecticides are urgently needed.

PMID- 24589250
TI  - Caval seminoma thrombus on FDG PET/CT.

PMID- 24589251
TI  - Parameters of heart rate variability can predict prolonged asystole before head
      up tilt table test.
AB  - BACKGROUND: We aimed to evaluate whether heart rate variability (HRV) could
      predict prolonged asystole before head-up tilt table test (HUTT) by comparing
      time domain HRV parameters of patients with type 2B vasovagal syncope (VVS) and
      patients with other types of VVS. METHODS: Ninety-eight patients who examined
      with 24-hour Holter electrocardiogram monitoring before HUTT and diagnosed with
      VVS were enrolled. Patients were divided into two groups in accordance with their
      VVS type as group 1 (n = 43) consisting of patients with type 2B VVS and group 2
      (n = 57) consisting of patients with other types of VVS. Time domain HRV
      parameters (SDNN, SDANN, SDNN index, RMSSD, pNN50) of two groups were compared.
      ROC curve analysis was performed to predict best cutoff values that could
      prognosticate occurrence of prolonged asystole during HUTT. RESULTS: SDNN, SDANN,
      SDNN index values were significantly longer for group 1 compared to group 2 (P =
      0.009, P = 0.006, P = 0.004; respectively). While a SDNN cutoff value of >=151 ms
      predicted occurrence of type 2B VVS before HUTT with 69% sensitivity and 56%
      specificity, a SDANN value of >=164 ms had 47% sensitivity and 87% specificity
      and a SDNN index value of >=102 ms showed 40% sensitivity and 85% specificity.
      CONCLUSIONS: In our study, we tried to demonstrate prediction of prolonged
      asystole by analyzing HRV parameters before HUTT. We found out that time domain
      HRV parameters were longer in patients with type 2B VVS than patients with other
      types of VVS. Our results need to be supported by extensive studies.

PMID- 24589249
TI  - Consumption of predefined 'Nordic' dietary items in ten European countries - an
      investigation in the European Prospective Investigation into Cancer and Nutrition
      (EPIC) cohort.
AB  - OBJECTIVE: Health-beneficial effects of adhering to a healthy Nordic diet index
      have been suggested. However, it has not been examined to what extent the
      included dietary components are exclusively related to the Nordic countries or if
      they are part of other European diets as well, suggesting a broader preventive
      potential. The present study describes the intake of seven a priori defined
      healthy food items (apples/pears, berries, cabbages, dark bread, shellfish, fish
      and root vegetables) across ten countries participating in the European
      Prospective Investigation into Cancer and Nutrition (EPIC) and examines their
      consumption across Europe. DESIGN: Cross-sectional study. A 24 h dietary recall
      was administered through a software program containing country-specific recipes.
      Sex-specific mean food intake was calculated for each centre/country, as well as
      percentage of overall food groups consumed as healthy Nordic food items. All
      analyses were weighted by day and season of data collection. SETTING: Multi
      centre, European study. SUBJECTS: Persons (n 36 970) aged 35-74 years,
      constituting a random sample of 519 978 EPIC participants. RESULTS: The highest
      intakes of the included diet components were: cabbages and berries in Central
      Europe; apples/pears in Southern Europe; dark bread in Norway, Denmark and
      Greece; fish in Southern and Northern countries; shellfish in Spain; and root
      vegetables in Northern and Central Europe. Large inter-centre variation, however,
      existed in some countries. CONCLUSIONS: Dark bread, root vegetables and fish are
      strongly related to a Nordic dietary tradition. Apples/pears, berries, cabbages,
      fish, shellfish and root vegetables are broadly consumed in Europe, and may thus
      be included in regional public health campaigns.

PMID- 24589252
TI  - The antibacterial toxin colicin N binds to the inner core of lipopolysaccharide
      and close to its translocator protein.
AB  - Colicins are a diverse family of large antibacterial protein toxins, secreted by
      and active against Escherichia coli and must cross their target cell's outer
      membrane barrier to kill. To achieve this, most colicins require an abundant
      porin (e.g. OmpF) plus a low-copy-number, high-affinity, outer membrane protein
      receptor (e.g. BtuB). Recently, genetic screens have suggested that colicin N
      (ColN), which has no high-affinity receptor, targets highly abundant
      lipopolysaccharide (LPS) instead. Here we reveal the details of this interaction
      and demonstrate that the ColN receptor-binding domain (ColN-R) binds to a
      specific region of LPS close to the membrane surface. Data from in vitro studies
      using calorimetry and both liquid- and solid-state NMR reveal the interactions
      behind the in vivo requirement for a defined oligosaccharide region of LPS.
      Delipidated LPS (LPS(Delta) (LIPID) ) shows weaker binding; and thus full
      affinity requires the lipid component. The site of LPS binding means that ColN
      will preferably bind at the interface and thus position itself close to the
      surface of its translocon component, OmpF. ColN is, currently, unique among
      colicins in requiring LPS and, combined with previous data, this implies that the
      ColN translocon is distinct from those of other known colicins. 

PMID- 24589253
TI  - Should non-steroidal anti-inflammatory drugs be used continuously in ankylosing
      spondylitis?
AB  - OBJECTIVE: The 2010 update of ASAS/EULAR recommendations for managing ankylosing
      spondylitis (AS) specify that continuous non-steroidal anti-inflammatory drug
      (NSAID) treatment should be preferred in patients with persistently active,
      symptomatic disease. Here, our objective was to assess whether continuous NSAID
      therapy improves disease control and influences radiographic progression compared
      to on-demand therapy. We also assessed the safety profiles of both regimens.
      METHODS: We performed a review by searching the PubMed and Embase databases using
      two MeSH term combinations to compare continuous and on-demand NSAID therapy in
      terms of disease control, radiographic progression, and safety. RESULTS: The only
      study evaluating the impact of continuous NSAID therapy on disease control showed
      no significant difference with on-demand therapy. In four studies, continuous
      treatment was associated with slower radiographic progression, as assessed in
      three studies using the modified Stoke Ankylosing Spondylitis Spinal Score (m
      SASSS). Three studies compared the safety of continuous and on-demand celecoxib,
      two in osteoarthritis and one in AS, and found no significant differences
      regarding the usual side effects of Cox-2 inhibitors. CONCLUSIONS: Several
      studies showed slower radiographic progression with continuous NSAID therapy in
      AS. No studies demonstrated superiority of continuous NSAID therapy regarding
      symptom control. Continuous NSAID therapy (at least with Cox-2 inhibitors) does
      not modify safety compared to on-demand therapy.

PMID- 24589254
TI  - An arthro-dermato-pulmonary syndrome associated with anti-MDA5 antibodies.

PMID- 24589255
TI  - Feasibility of ambulatory withdrawal management delivered in a NSW drug health
      service and correlates of completion.
AB  - OBJECTIVE: The aim of the present study was to assess short-term ambulatory
      withdrawal management (AWM) outcomes at a drug health service (DHS) in Sydney,
      Australia, in the absence of specific funding. METHODS: A clinic file audit
      review was conducted of patients who commenced AWM at the service during January
      2009-June 2011. Successful completion was defined as daily attendance with <=1
      missed day, or transfer onto opioid substitution treatment. RESULTS: Of 110
      episodes, 69 (63%) were completed. Median patient age was 35 years (range 18-71
      years), and most patients (68%) were male. Patients presented primarily for
      cannabis (33%) or alcohol (30%) withdrawal, followed by heroin (19%) or other
      opioids (6%), and benzodiazepines (12%). Completion rates varied from 86% for non
      heroin opioids to 31% for benzodiazepines. Older age was associated with
      increased completion: 76% of those aged >35 years completed compared with 50% of
      those <=35 years of age. Only 46% of women who commenced withdrawal management
      completed compared with 71% of men. CONCLUSIONS Most people commencing AWM at the
      DHS completed the program, indicating AWM can be performed at public drug and
      alcohol clinics. Service improvements may help increase completion rates among
      women and patients withdrawing from benzodiazepines. What is known about the
      topic? WM is not a standalone treatment for substance dependence, but is commonly
      a first attempt at treatment. AWM is often more acceptable to patients, and
      cheaper, than in-patient services. What does this paper add? About two-thirds of
      patients entering an AWM program operating since 2001 continue to complete the
      program. What are the implications for practitioners? AWM can be carried out
      successfully through public drug and alcohol services, although clinic staff
      support is important.

PMID- 24589256
TI  - Identification of pathogen genomic variants through an integrated pipeline.
AB  - BACKGROUND: Whole-genome sequencing represents a powerful experimental tool for
      pathogen research. We present methods for the analysis of small eukaryotic
      genomes, including a streamlined system (called Platypus) for finding single
      nucleotide and copy number variants as well as recombination events. RESULTS: We
      have validated our pipeline using four sets of Plasmodium falciparum drug
      resistant data containing 26 clones from 3D7 and Dd2 background strains,
      identifying an average of 11 single nucleotide variants per clone. We also
      identify 8 copy number variants with contributions to resistance, and report for
      the first time that all analyzed amplification events are in tandem. CONCLUSIONS:
      The Platypus pipeline provides malaria researchers with a powerful tool to
      analyze short read sequencing data. It provides an accurate way to detect SNVs
      using known software packages, and a novel methodology for detection of CNVs,
      though it does not currently support detection of small indels. We have validated
      that the pipeline detects known SNVs in a variety of samples while filtering out
      spurious data. We bundle the methods into a freely available package.

PMID- 24589257
TI  - Anomalous temperature dependence of speed of sound of bulk poly(N
      isopropylacrylamide) hydrogels near the phase transition.
AB  - Bulk Poly(N-isopropylacrylamide) (PNIPAm) hydrogels are thermally responsive
      polymers that undergo a sharp volumetric phase transition around its lower
      critical solution temperature of 33  degrees C. The physical characteristics of
      bulk, micro-, and nano-form PNIPAm hydrogel have been well-studied, and have
      applications ranging from biomedical devices to mechanical actuators. An
      important physical characteristics which reveals lack of available information is
      speed of sound. Prior studies have utilized Brillouin scattering, multi-echo
      reflection ultrasound spectroscopy, the sing-around method, and others in
      measuring the speed of sound. We use a planar resonant cavity with bulk PNIPAm
      hydrogel in aqueous solution to determine the temperature dependent speed of
      sound around the lower critical solution temperature. The results show sharp
      nonmonotonic behavior of the sound velocity in vicinity of the phase transition.

PMID- 24589258
TI  - Impact of thermal effects induced by ultrasound on viability of rat C6 glioma
      cells.
AB  - In order to have consistent and repeatable effects of sonodynamic therapy (SDT)
      on various cancer cells or tissue lesions we should be able to control a
      delivered ultrasound energy and thermal effects induced. The objective of this
      study was to investigate viability of rat C6 glioma cells in vitro depending on
      the intensity of ultrasound in the region of cells and to determine the exposure
      time inducing temperature rise above 43  degrees C, which is known to be toxic
      for cells. For measurements a planar piezoelectric transducer with a diameter of
      20 mm and a resonance frequency of 1.06 MHz was used. The transducer generated
      tone bursts with 94 MUs duration, 0.4 duty-cycle and initial intensity ISATA
      (spatial averaged, temporal averaged) varied from 0.33 W/cm(2) to 8 W/cm(2)
      (average acoustic power varied from 1 W to 24 W). The rat C6 glioma cells were
      cultured on a bottom of wells in 12-well plates, incubated for 24h and then
      exposed to ultrasound with measured acoustic properties, inducing or causing no
      thermal effects leading to cell death. Cell viability rate was determined by MTT
      assay (a standard colorimetric assay for assessing cell viability) as the ratio
      of the optical densities of the group treated by ultrasound to the control group.
      Structural cellular changes and apoptosis estimation were observed under a
      microscope. Quantitative analysis of the obtained results allowed to determine
      the maximal exposure time that does not lead to the thermal effects above 43 
      degrees C in the region of cells for each initial intensity of the tone bursts
      used as well as the threshold intensity causing cell death after 3 min exposure
      to ultrasound due to thermal effects. The averaged threshold intensity was found
      to be about 5.7 W/cm(2).

PMID- 24589259
TI  - Invasive neuroendocrine carcinoma of the breast: a population-based study from
      the surveillance, epidemiology and end results (SEER) database.
AB  - BACKGROUND: Neuroendocrine carcinoma (NEC) of the breast is a rare type of
      carcinoma that has not been well studied or characterized. Of the limited number
      of studies reported in the literature, most are case reports. A few small
      retrospective series studies have been reported. METHODS: We reviewed data on 142
      cases of mammary NEC recorded in the surveillance, epidemiology, and end results
      (SEER) database during 2003-2009 and evaluated disease incidence and patient age,
      sex, and race/ethnicity; clinicopathologic characteristics; and survival in
      comparison to invasive mammary carcinoma, not otherwise specified. We also
      performed univariate and multivariate analyses to identify prognostic factors in
      this disease. RESULTS: Review of the 142 SEER cases revealed that NEC is an
      aggressive variant of invasive mammary carcinoma. It generally occurred in older
      women (>60 years); present with larger tumor size (>20 mm), higher histologic
      grade, and higher clinical stage; and result in shorter overall survival and
      disease-specific survival than invasive mammary carcinoma, not otherwise
      specified (IMC-NOS). Overall survival and disease-specific survival were shorter
      in NEC at each stage than in IMC-NOS of the same stage. Furthermore, when all NEC
      and IMC-NOS cases were pooled together, neuroendocrine differentiation itself was
      an adverse prognostic factor independent of other known prognostic factors,
      including age, tumor size, nodal status, histologic grade, estrogen/progesterone
      receptor status, and therapy. CONCLUSIONS: NEC is a rare but aggressive type of
      mammary carcinoma. Novel therapeutic approaches should be explored for this
      uniquely clinical entity.

PMID- 24589260
TI  - Hemoglobin s polymerization and red cell membrane changes.
AB  - Different pathways lead from the simple point mutation in hemoglobin to the
      membrane changes that characterize the altered interaction of the sickle red
      blood cell with its environment, including endothelial cells, white blood cells,
      and platelets. Polymerization and oxidation-induced damage to both lipid and
      protein components of the red cell membrane, as well as the generation of
      bioreactive membrane material (microparticles), has a profound effect on all
      tissues and organs, and defines the vasculopathy of the patient with sickle cell
      disease. 

PMID- 24589261
TI  - Ischemia-reperfusion injury in sickle cell anemia: relationship to acute chest
      syndrome, endothelial dysfunction, arterial vasculopathy, and inflammatory pain.
AB  - Ischemia-reperfusion (I/R) physiology, also called reperfusion injury, instigates
      vascular and tissue injury in human disease states. This review describes why
      sickle cell anemia should be conceptualized in this fashion and how I/R
      physiology explains the genesis of characteristic aspects of vascular
      pathobiology and clinical disease in sickle cell anemia. The nature of I/R and
      its relevance to sickle cell anemia are discussed, with an emphasis on the acute
      chest syndrome, endothelial dysfunction with aberrant vasoregulation, circle of
      Willis vasculopathy, and inflammatory pain. Viewing sickle disease from this
      perspective elucidates defining pathophysiology and identifies a host of novel
      potential therapeutic targets. 

PMID- 24589262
TI  - Gene therapy for hemoglobinopathies: the state of the field and the future.
AB  - After nearly two decades of struggle, gene therapy for hemoglobinopathies using
      vectors carrying beta or gamma-globin gene has finally reached the clinical
      doorsteps. This was made possible by advances made in our understanding of
      critical regulatory elements required for high level of globin gene expression
      and improved gene transfer vectors and methodologies. Development of gene editing
      technologies and reprogramming somatic cells for regenerative medicine holds the
      promise of genetic correction of hemoglobinopathies in the future. This article
      will review the state of the field and the upcoming technologies that will allow
      genetic therapeutic correction of hemoglobinopathies. 

PMID- 24589265
TI  - Does erythropoietin have a role in the treatment of beta-hemoglobinopathies?
AB  - This review presents the indications and contraindications (pros and cons) for
      the potential use of erythropoietin (Epo) as a treatment in beta-thalassemia and
      sickle cell anemia (SCA). Its high cost and route of administration (by
      injection) are obvious obstacles, especially in underdeveloped countries, where
      thalassemia is prevalent. We believe that from the data summarized in this
      review, the time has come to define, by studying in vitro and in vivo models, as
      well as by controlled clinical trials, the rationale for treating patients with
      various forms of thalassemia and SCA with Epo alone or in combination with other
      medications.

PMID- 24589264
TI  - Targeted fetal hemoglobin induction for treatment of beta hemoglobinopathies.
AB  - Fetal globin (gamma globin; HBG) is normally expressed during fetal life and
      prevents the clinical manifestations of beta hemoglobinopathies before birth. HBG
      genes are normally integrated in hematopoietic stem cells in all humans, and are
      at least partially amenable to reactivation. Inducing expression of fetal globin
      (HBG) gene expression to 60% to 70% of alpha globin synthesis produces a beta
      thalassemia trait phenotype, and reduces anemia. Tailoring combinations of
      therapeutics to patient subsets characterized for quantitative trait loci which
      modulate basal fetal hemoglobin and erythroid cell survival should provide
      effective amelioration of clinical symptoms in beta-thalassemia and sickle cell
      disease. 

PMID- 24589266
TI  - Inflammatory mediators of endothelial injury in sickle cell disease.
AB  - Inflammation plays a critical role in the complex pathophysiology of sickle cell
      disease and drives both the acute and chronic processes leading to vascular
      injury. Mediators of inflammation, such as cellular adhesion molecules,
      cytokines, leukotrienes, and nuclear factor kappaB signaling factors, represent
      potential therapeutic targets in sickle cell disease. 

PMID- 24589263
TI  - Therapeutic strategies to alter the oxygen affinity of sickle hemoglobin.
AB  - The pathophysiology of sickle cell disease involves the polymerization of sickle
      hemoglobin in its T state, which develops under low oxygen saturation. One
      therapeutic strategy is to develop pharmacologic agents to stabilize the R state
      of hemoglobin, which has higher oxygen affinity and is expected to have slower
      kinetics of polymerization, potentially delaying the sickling of red cells during
      circulation. This strategy has stimulated the investigation of aromatic
      aldehydes, aspirin derivatives, thiols, and isothiocyanates that can stabilize
      the R state of hemoglobin in vitro. One representative aromatic aldehyde agent, 5
      hydoxymethyl-2-furfural, protects sickle cell mice from the effects of hypoxia. 

PMID- 24589268
TI  - Alterations of the arginine metabolome in sickle cell disease: a growing
      rationale for arginine therapy.
AB  - Low global arginine bioavailability (GAB) is associated with numerous
      complications of SCD including early mortality. Mechanisms of arginine
      dysregulation involve a complex paradigm of excess activity of the arginine
      consuming enzyme arginase, elevated levels of asymmetric dimethylarginine,
      altered intracellular arginine transport, and nitric oxide synthase dysfunction.
      Restoration of GAB through exogenous supplementation is therefore, a promising
      therapeutic target. Studies of arginine therapy demonstrate efficacy in treating
      patients with leg ulcers, pulmonary hypertension risk, and pain. Co
      administration with hydroxyurea increases levels of nitrite and fetal hemoglobin.
      Addressing the alterations in the arginine metabolome may result in new
      strategies for treatment of SCD. 

PMID- 24589267
TI  - The role of adenosine signaling in sickle cell therapeutics.
AB  - Data suggest a role for adenosine signaling in the pathogenesis of sickle cell
      disease (SCD). Signaling through the adenosine A2A receptor (A2AR) has
      demonstrated beneficial effects. Activation of A2ARs decreases inflammation with
      SCD by blocking activation of invariant natural killer T cells. Decreased
      inflammation may reduce the severity of vasoocclusive crises. Adenosine signaling
      through the adenosine A2B receptor (A2BR) may be detrimental in SCD. Whether
      adenosine signaling predominantly occurs through A2ARs or A2BRs may depend on
      differing levels of adenosine and disease state (steady state versus crisis).
      There may be opportunities to develop novel therapeutic approaches targeting
      A2ARs and/or A2BRs for patients with SCD. 

PMID- 24589269
TI  - Cellular adhesion and the endothelium: P-selectin.
AB  - P-selectin on endothelial cell surfaces is central to impaired microvascular
      blood flow in sickle cell disease (SCD). Restoration of blood flow is expected to
      provide therapeutic benefit for SCD patients, whatever the mechanism of action of
      the treatment. Long-term oral administration of a P-selectin-blocking agent
      potentially improves blood flow and averts acute painful vaso-occlusive crises in
      patients with SCD. This review focuses on the pathophysiology of the impairment
      of microvascular blood flow in SCD with an emphasis on the role of P-selectin and
      summarizes the status of development of antiselectin therapies as a means of
      improving microvascular flow. 

PMID- 24589270
TI  - Cellular adhesion and the endothelium: E-selectin, L-selectin, and pan-selectin
      inhibitors.
AB  - The pathophysiology of vasoocclusion is thought to involve a wide variety of
      adhesive interactions involving erythrocytes, leukocytes, and the endothelium.
      Selectins are expressed by leukocytes, platelets, and the endothelium, among
      other tissues. They contribute to a wide variety of physiologically important
      cell-cell interactions, including adhesion of all types of blood cells to the
      endothelium. In vitro, in vivo, and early-phase clinical studies suggest that E
      selectin and pan-selectin inhibitors may be promising new therapeutic agents for
      the treatment of vasoocclusion in sickle cell disease. 

PMID- 24589271
TI  - Role of the hemostatic system on sickle cell disease pathophysiology and
      potential therapeutics.
AB  - Recent studies suggest that sickle cell disease (SCD) is a hypercoagulable state
      contributing to vaso-occlusive events in the microcirculation, resulting in acute
      and chronic sickle cell-related organ damage. In this article, we review the
      existing evidence for contribution of hemostatic system perturbation to SCD
      pathophysiology. We also review the data showing increased risk of thromboembolic
      events, particularly newer information on the incidence of venous
      thromboembolism. Finally, the potential role of platelet inhibitors and
      anticoagulants in SCD is briefly reviewed. 

PMID- 24589274
TI  - Emerging therapy in hemoglobinopathies: lessons from the past and optimism for
      the future.

PMID- 24589272
TI  - Modulators of erythropoiesis: emerging therapies for hemoglobinopathies and
      disorders of red cell production.
AB  - Use of new compound such as inhibitors of JAK2 or transforming growth factor beta
      like molecules might soon revolutionize the treatment of beta-thalassemia and
      related disorders. However, this situation requires careful optimization, noting
      the potential for off-target immune suppression for JAK2 inhibitors and the lack
      of mechanistic insights for the use of the ligand trap soluble molecules that
      sequester ligands of activin receptor IIA and B. 

PMID- 24589273
TI  - Modulation of hepcidin as therapy for primary and secondary iron overload
      disorders: preclinical models and approaches.
AB  - In this article, the authors discuss new approaches to treating iron overload
      diseases using hepcidin mimetics or by modulating endogenous hepcidin expression.
      In particular, the authors discuss lipid nanoparticle encapsulated siRNA and
      antisense oligonucleotide-mediated inhibition of TMPRSS6, an upstream regulator
      of hepcidin, and treatment with transferrin or hepcidin mimetics, including the
      recently described minihepcidins. In each case, in animal models of beta
      thalassemia, not only do the interventions affect iron absorption but they also
      act as disease-modifying agents that ameliorate the ineffective erythropoiesis. 

PMID- 24589276
TI  - Effect of acetylcholinesterase (AChE) point-of-care testing in OP poisoning on
      knowledge, attitudes and practices of treating physicians in Sri Lanka.
AB  - BACKGROUND: Toxicology and Emergency medicine textbooks recommend measurement of
      acetylcholinesterase (AChE) in all symptomatic cases of organophosphorus (OP)
      poisoning but laboratory facilities are limited in rural Asia. The accuracy of
      point-of-care (POC) acetylcholinesterase testing has been demonstrated but it
      remains to be shown whether results would be valued by clinicians. This study
      aims to assess the effect of seeing AChE POC test results on the knowledge,
      attitudes and practices of doctors who frequently manage OP poisoning. METHODS:
      We surveyed 23 clinicians, who had different levels of exposure to seeing AChE
      levels in OP poisoned patients, on a) knowledge of OP poisoning and biomarker
      interpretation, b) attitudes towards AChE in guiding poison management, oxime
      therapy and discharge decisions, and c) practices of ordering AChE in poisoning
      scenarios. RESULTS: An overall high proportion of doctors valued the test (68
      89%). However, we paradoxically found that doctors who were more experienced in
      seeing AChE results valued the test less. Lower proportions valued the test in
      guidance of acute poisoning management (50%, p = 0.015) and guidance of oxime
      therapy (25%, p = 0.008), and it was apparent it would not generally be used to
      facilitate early discharge. The highest proportion of respondents valued it on
      admission (p < 0.001). A lack of correlation of test results with the clinical
      picture, and a perception that the test was a waste of money when compared to
      clinical observation alone were also comments raised by some of the
      respondents.Greater experience with seeing AChE test results was associated with
      increased knowledge (p = 0.034). However, a disproportionate lack of knowledge on
      interpretation of biomarkers and the pharmacology of oxime therapy (12-50%) was
      noted, when compared with knowledge on the mechanism of OP poisoning and
      management (78-90%). CONCLUSIONS: Our findings suggest an AChE POC test may not
      be valued by rural doctors. The practical use of AChE in OP poisoning management
      is complex, and a poor understanding of how to interpret test results may have
      affected its perceived utility. Future research should evaluate the impact of
      providing both AChE and training in interpretation on clinicians' attitudes and
      practice.

PMID- 24589277
TI  - Application of single shot free-breathing fast imaging employing steady state
      sequence in cardiac magnetic resonance imaging.
AB  - OBJECTIVE: To investigate the imaging quality of single shot (SS) fast imaging
      employing steady state (FIESTA) sequence in contrast-enhanced cardiac magnetic
      resonance (MR) examination, in comparison with the segmented inversion recovery
      2D fast gradient echo (IR FGRE) sequence. MATERIALS AND METHODS: Fifty-two cases
      with suspected or known heart disease were enrolled in this study, including 24
      patients who had enhanced myocardium in myocardial delayed enhancement (MDE). We
      analyzed the imaging quality of the sequences by measuring the myocardium and
      blood pool signal-to-noise ratios (SNR) and the contrast-to-noise ratios (CNR) of
      blood pool relative to normal myocardium and of enhanced myocardium relative to
      normal myocardium and compared the new sequences with traditional sequence.
      RESULTS: The scanning time of SS FIESTA was significantly shortened as compared
      to IR FGRE. The differences in the image quality scores, enhanced myocardium (EM)
      mass and percentages, SNR(bp), SNR(myo), CNR(myo/bp) and CNR(l/bg) were not
      statistically significant between SS FIESTA and IR FGRE (P > 0.05). However, the
      difference in CNR(em/myo) was statistically significant between SS FIESTA and IR
      FGRE (P < 0.0001), with CNR(em/myo) of IR FGRE higher than SS FIESTA. CONCLUSION:
      Single shot FIESTA speeded up the acquisition time, halving it to (27.6 +/- 1.8
      s) instead of 146 + 13.8 s (IR FGRE), it had higher SNR and CNR, and its image
      quality did not differ significantly from IR FGRE. The SS FIESTA is more suitable
      for patients with severely heart diseases or those unable to hold breath. 3D IR
      FGRE sequence had higher SNR(myo) than the others and it is suitable for
      displaying the subendocardial scar. However, it has more artefacts and poor
      imaging quality than IR FGRE.

PMID- 24589278
TI  - Fabrication of TiN nanostructure as a hydrogen peroxide sensor by oblique angle
      deposition.
AB  - Nanostructured titanium nitride (TiN) films with varying porosity were prepared
      by the oblique angle deposition technique (OAD). The porosity of films increases
      as the deposition angle becomes larger. The film obtained at an incident angle of
      85 degrees  exhibits the best catalytic activity and sensitivity to hydrogen
      peroxide (H2O2). This could be attributed to its largest contact area with the
      electrolyte. An effective approach is thus proposed to fabricate TiN
      nanostructure as H2O2 sensor by OAD. 

PMID- 24589280
TI  - Nanoscale focused ion beam tomography of single bacterial cells for assessment of
      antibiotic effects.
AB  - Antibiotic resistance is a major risk to human health, and to provide valuable
      insights into mechanisms of resistance, innovative methods are needed to examine
      the cellular responses to antibiotic treatment. Focused ion beam tomography is
      proposed to image and assess the detailed three-dimensional (3D) ultrastructure
      of single bacterial cells. By iteratively removing slices of thickness in the
      order of 10 nm, high magnification 2D images can be acquired by scanning electron
      microscopy at single-digit nanometer resolution. In this study, Klebsiella
      pneumoniae was treated with polymyxin B, and 3D models of both cell envelope and
      cytoplasm regions containing the nucleoid and ribosomes were reconstructed. The
      3D volume containing the nucleoid and ribosomes was significantly smaller, and
      the cell length along the longitudinal axis was extended by 40% in the treated
      cells, implying stress responses to the drug treatment. More than a 200% increase
      in protrusions per unit surface area on the cell envelope was observed in the
      curvature analysis after treatment. Experiments by conventional transmission
      electron microscopy and atomic force microscopy were also performed, followed by
      comparison and discussions. In conclusion, the proposed 3D imaging method and
      associated analysis provide a unique tool for the assessment of antibiotic
      effects on multidrug-resistant bacteria at nanometer resolution. 

PMID- 24589281
TI  - Left atrial remodeling in hypertrophic cardiomyopathy and susceptibility markers
      for atrial fibrillation identified by cardiovascular magnetic resonance.
AB  - In hypertrophic cardiomyopathy (HC), atrial fibrillation (AF) is an important
      determinant of clinical deterioration due to heart failure or embolic stroke.
      This study characterizes left atrial (LA) structural and functional parameters to
      establish markers predictive of AF risk, using cardiovascular magnetic resonance
      (CMR) imaging. We studied 427 consecutive patients with HC in sinus rhythm with
      CMR (age 44+/-18 years), including 41 who developed clinically overt AF after
      study entry (2.6+/-2.1 years), 49 patients with AF before CMR, 337 patients with
      HC but without AF, and 244 normal controls. LA chamber was assessed for absolute
      and indexed end-diastolic volume (LAEDV), end-systolic volume, and percent
      ejection fraction (LAEF). In the 41 prospectively studied patients with HC who
      developed AF during follow-up, LAEDV was significantly greater than in patients
      without AF (146+/-48 vs 107+/-37 ml) or in normal controls (81+/-24 ml, p<0.001).
      Percent LAEF was lower in patients developing AF (36+/-10%) than without AF (46+/
      12%) or controls (55+/-9%, p<0.001). Multivariate analysis identified LAEF
      (<38%), LAEDV (>=118 ml), and age (>=40 years) as independently associated with
      AF occurrence. In conclusion, CMR measures of LA remodeling and dysfunction
      reliably identified patients with HC at risk for future development of AF.
      Decrease in LAEF represents a strong novel marker of susceptibility to AF in this
      disease.

PMID- 24589279
TI  - Patterns of adherence to antiretroviral therapy and HIV drug resistance over time
      in the Stratall ANRS 12110/ESTHER trial in Cameroon.
AB  - OBJECTIVES: The emergence of HIV drug resistance is a crucial issue in Africa,
      where second-line antiretroviral therapy (ART) is limited, expensive and complex.
      We assessed the association between adherence patterns and resistance emergence
      over time, using an adherence measure that distinguishes low adherence from
      treatment interruptions, in rural Cameroon. METHODS: We performed a cohort study
      among patients receiving nonnucleoside reverse transcriptase inhibitor (NNRTI)
      based ART in nine district hospitals, using data from the Stratall trial (2006
      2010). Genotypic mutations associated with antiretroviral drug resistance were
      assessed when 6-monthly HIV viral loads were > 5000 HIV-1 RNA copies/mL. ART
      adherence data were collected using face-to-face questionnaires. Combined
      indicators of early (1-3 months) and late (6 months to t - 1; t is the time point
      when the resistance had been detected) adherence were constructed. Multivariate
      logistic regression and Cox models were used to assess the association between
      adherence patterns and early (at 6 months) and late (after 6 months) resistance
      emergence, respectively. RESULTS: Among 456 participants (71% women; median age
      37 years), 45 developed HIV drug resistance (18 early and 27 late). Early low
      adherence (< 80%) and treatment interruptions (> 2 days) were associated with
      early resistance [adjusted odds ratio (95% confidence interval) 8.51 (1.30-55.61)
      and 5.25 (1.45-18.95), respectively]. Early treatment interruptions were also
      associated with late resistance [adjusted hazard ratio (95% confidence interval)
      3.72 (1.27-10.92)]. CONCLUSIONS: The emergence of HIV drug resistance on first
      line NNRTI-based regimens was associated with different patterns of adherence
      over time. Ensuring optimal early adherence through specific interventions,
      adequate management of drug stocks, and viral load monitoring is a clinical and
      public health priority in Africa.

PMID- 24589284
TI  - Daring to be different: colicin N finds another way.
AB  - The mechanisms by which colicins, protein toxins produced by Escherichia coli,
      kill other E. coli, have become much better understood in recent years. Most
      colicins initially bind to an outer membrane protein receptor, and then search
      for a separate nearby outer membrane protein translocator that serves as a
      pathway into target cells. Many colicins use the outer membrane porin, OmpF, as
      that translocator, while using a different primary receptor. Colicin N is unique
      among known colicins in that only OmpF had been identified as being required for
      uptake of the colicin and it was presumed to somehow serve as both receptor and
      translocator. Genetic screens also identified a number of genes required for
      lipopolysaccharide (LPS) synthesis as uniquely required for killing by colicin N,
      but not by other colicins. Johnson et al. show that the receptor-binding domain
      of colicin N binds to LPS, and does not require OmpF for that binding. LPS of a
      minimal length is required for binding, explaining the requirement for specific
      elements of the LPS biosynthetic pathway. For colicin N, the receptor-binding
      domain does not recognize a protein, but rather the most abundant component of
      the outer membrane itself, LPS. 

PMID- 24589285
TI  - Centers of excellence for neuromodulation: a critical proposal.

PMID- 24589287
TI  - Whole genome amplification: watch out for the bias!

PMID- 24589286
TI  - Neurotech report.

PMID- 24589288
TI  - Community differentiation and population enrichment of Sargasso Sea
      bacterioplankton in the euphotic zone of a mesoscale mode-water eddy.
AB  - Eddies are mesoscale oceanographic features (~ 200 km diameter) that can cause
      transient blooms of phytoplankton by shifting density isoclines in relation to
      light and nutrient resources. To better understand how bacterioplankton respond
      to eddies, we examined depth-resolved distributions of bacterial populations
      across an anticyclonic mode-water eddy in the Sargasso Sea. Previous work on this
      eddy has documented elevated phytoplankton productivity and diatom abundance
      within the eddy centre with coincident bacterial productivity and biomass maxima.
      We illustrate bacterial community shifts within the eddy centre, differentiating
      populations uplifted along isopycnals from those enriched or depleted at horizons
      of enhanced bacterial and primary productivity. Phylotypes belonging to the
      Roseobacter, OCS116 and marine Actinobacteria clades were enriched in the eddy
      core and were highly correlated with pigment-based indicators of diatom
      abundance, supporting developing hypotheses that members of these clades
      associate with phytoplankton blooms. Typical mesopelagic clades (SAR202, SAR324,
      SAR406 and SAR11 IIb) were uplifted within the eddy centre, increasing bacterial
      diversity in the lower euphotic zone. Typical surface oligotrophic clades
      (SAR116, OM75, Prochlorococcus and SAR11 Ia) were relatively depleted in the eddy
      centre. The biogeochemical context of a bloom-inducing eddy provides insight into
      the ecology of the diverse uncultured bacterioplankton dominating the
      oligotrophic oceans.

PMID- 24589290
TI  - A systematic review of 1143 parapharyngeal space tumors reported over 20 years.
AB  - Parapharyngeal space tumours are rare and most clinicians will only see a small
      number during their career. We performed a systematic review of 1143
      parapharyngeal space tumors published in the past 20 years to increase cumulative
      experience. A systematic literature review was performed and data on histological
      diagnosis, presentation, surgical approach and postoperative complications of
      cases published between 1989 and 2009 were compiled and reviewed. The systematic
      review identified a total of 1143 parapharyngeal space tumors presented in 17
      studies. A majority (82%) were benign and 18% were malignant. The most common
      presentation was a cervical mass (50%) or an intraoral mass (47%). Approximately
      70 different histologic subtypes of parapharyngeal space tumors were reported in
      the cumulative series. The most common primary lesion was a pleomorphic adenoma
      (34%). Ninety-five percent of patients underwent surgery. The most frequent
      approach and used to excise the lesions was the cervical approach (48%) and the
      commonest complication was the vagus nerve injury seen in 14% of the cases.

PMID- 24589289
TI  - Assessment of four DNA fragments (COI, 16S rDNA, ITS2, 12S rDNA) for species
      identification of the Ixodida (Acari: Ixodida).
AB  - BACKGROUND: The 5' region of cytochrome oxidase I (COI) is the standard marker
      for DNA barcoding. However, COI has proved to be of limited use in identifying
      some species, and for some taxa, the coding sequence is not efficiently amplified
      by PCR. These deficiencies lead to uncertainty as to whether COI is the most
      suitable barcoding fragment for species identification of ticks. METHODS: In this
      study, we directly compared the relative effectiveness of COI, 16S ribosomal DNA
      (rDNA), nuclear ribosomal internal transcribed spacer 2 (ITS2) and 12S rDNA for
      tick species identification. A total of 307 sequences from 84 specimens
      representing eight tick species were acquired by PCR. Besides the 1,834 published
      sequences of 189 tick species from GenBank and the Barcode of Life Database, 430
      unpublished sequences representing 59 tick species were also successfully
      screened by Bayesian analyses. Thereafter, the performance of the four DNA
      markers to identify tick species was evaluated by identification success rates
      given by these markers using nearest neighbour (NN), BLASTn, liberal tree-based
      or liberal tree-based (+threshold) methods. RESULTS: Genetic divergence analyses
      showed that the intra-specific divergence of each marker was much lower than the
      inter-specific divergence. Our results indicated that the rates of correct
      sequence identification for all four markers (COI, 16S rDNA, ITS2, 12S rDNA) were
      very high (> 96%) when using the NN methodology. We also found that COI was not
      significantly better than the other markers in terms of its rate of correct
      sequence identification. Overall, BLASTn and NN methods produced higher rates of
      correct species identification than that produced by the liberal tree-based
      methods (+threshold or otherwise). CONCLUSIONS: As the standard DNA barcode, COI
      should be the first choice for tick species identification, while 16S rDNA, ITS2,
      and 12S rDNA could be used when COI does not produce reliable results. Besides,
      NN and BLASTn are efficient methods for species identification of ticks.

PMID- 24589291
TI  - Evaluation of a tailored, multi-component intervention for implementation of
      evidence-based clinical practice guidelines in primary care physical therapy: a
      non-randomized controlled trial.
AB  - BACKGROUND: Clinical practice guidelines are important for transmitting research
      findings into practice and facilitating the application of evidence-based
      practice (EBP). There is a paucity of knowledge about the impact of guideline
      implementation strategies in primary care physical therapy. The aim of this study
      was to evaluate the effect of a guideline implementation intervention in primary
      care physical therapy in western Sweden. METHODS: An implementation strategy
      based on theory and current evidence was developed. A tailored, multi-component
      implementation intervention, addressing earlier identified determinants, was
      carried out in three areas comprising 28 physical therapy practices including 277
      physical therapists (PTs) (intervention group). In two adjacent areas, 171 PTs at
      32 practices received no intervention (control group). The core component of the
      intervention was an implementation seminar with group discussions. Among other
      components were a website and email reminders. Data were collected at baseline
      and follow-up with a web-based questionnaire. Primary outcomes were the self
      reported awareness of, knowledge of, access to, and use of guidelines. Secondary
      outcomes were self-reported attitudes toward EBP and guidelines. Analyses were
      performed using Pearson's chi2 test and approximative z-test. RESULTS: 168 PTs
      (60.6%) in the intervention group and 88 PTs (51.5%) in the control group
      responded to the follow-up questionnaire. 186/277 PTs (67.1%) participated in the
      implementation seminars, of which 97 (52.2%) responded. The proportions of PTs
      reporting awareness of (absolute difference in change 20.6%, p = 0.023),
      knowledge where to find (20.4%, p = 0.007), access to (21.7%, p < 0.001), and
      frequent use of (9.5%, NS) guidelines increased more in the intervention group
      than in the control group. The proportion of PTs reporting frequent guideline use
      after participation in the implementation seminar was 15.2% (p = 0.043) higher
      than the proportion in the control group. A higher proportion considered EBP
      helpful in decision making (p = 0.018). There were no other significant
      differences in secondary outcomes. CONCLUSIONS: A tailored, theory- and evidence
      informed, multi-component intervention for the implementation of clinical
      practice guidelines had a modest, positive effect on awareness of, knowledge of,
      access to, and use of guidelines, among PTs in primary care in western Sweden. In
      general, attitudes to EBP and guidelines were not affected.

PMID- 24589292
TI  - Evidence supporting the match/mismatch hypothesis of psychiatric disorders.
AB  - Chronic stress is one of the predominant environmental risk factors for a number
      of psychiatric disorders, particularly for major depression. Different hypotheses
      have been formulated to address the interaction between early and adult chronic
      stress in psychiatric disease vulnerability. The match/mismatch hypothesis of
      psychiatric disease states that the early life environment shapes coping
      strategies in a manner that enables individuals to optimally face similar
      environments later in life. We tested this hypothesis in female Balb/c mice that
      underwent either stress or enrichment early in life and were in adulthood further
      subdivided in single or group housed, in order to provide aversive or positive
      adult environments, respectively. We studied the effects of the environmental
      manipulation on anxiety-like, depressive-like and sociability behaviors and gene
      expression profiles. We show that continuous exposure to adverse environments
      (matched condition) is not necessarily resulting in an opposite phenotype
      compared to a continuous supportive environment (matched condition). Rather,
      animals with mismatched environmental conditions behaved differently from animals
      with matched environments on anxious, social and depressive like phenotypes.
      These results further support the match/mismatch hypothesis and illustrate how
      mild or moderate aversive conditions during development can shape an individual
      to be optimally adapted to similar conditions later in life. 

PMID- 24589293
TI  - Documentation of limitation of medical therapy at the time of a rapid response
      team call.
AB  - OBJECTIVES: The aims of the present study were to: (1) describe the documentation
      process of limitation of medical therapy (LMT) orders at the time of a rapid
      response team (RRT) call; and (2) compare documented LMT orders not associated
      with an RRT call (control, Group 1) with LMT orders documented at the time of an
      RRT call (Group 2). METHODS: A descriptive study, over a 6-month period (February
      August 2011), involving the review of the medical records of patients
      prospectively identified as either Group 1 or Group 2. RESULTS: There were 994
      RRT calls; of these, 50 patients (5%) had an LMT order documented by the RRT. A
      cardiac arrest was the trigger for the RRT for six patients (12%). Patients in
      Group 1 (n=50) and Group 2 were of similar median age (80.5 vs 78.5 years;
      P=0.30), LMTs were recorded at a similar time of day (15:30 vs 15:55 hours;
      P=0.52) and day of the week (weekend: 32% vs 35%; P=0.72). Comparing group 2 with
      Group 1, the RRT was less likely to document a not-for-resuscitation (NFR; 31
      (62%) vs 49 (98%); P<0.01) or a not-for-ICU (NFICU; 18 (36%) vs 41 (82%); P<0.01)
      order, but more likely to document a not-for-RRT call (NFRRT; 31 (62%) vs 22
      (44%); P=0.04) and modified RRT calling criteria (MRRT; 4 (8%) vs 0 (0%); P=0.04)
      orders. For Group 2 compared with Group 1 orders, involvement of the patient in
      the decision making process (9 (18%) vs 25 (50%); P<0.01) or the next of kin (29
      (58%) vs 45 (90%); P<0.01) was documented less often. CONCLUSIONS: Documentation
      of LMT orders at the time of an RRT call is less likely to include documented
      involvement of patients or their next of kin, and is more likely to be an NFRRT
      or MRRT order. These findings have implications for overall clinical governance.
      What is known about the topic? RRT are not infrequently involved in documenting
      LMT orders. What does this paper add? This is the first study in Australasia to
      look into the timing and circumstances surrounding the issuing of a NFR order
      during an RRT call. The study findings clarify the type of LMT orders documented
      by RRT and to what extent patients, their carers and senior medical staff are
      involved. What are the implications for practitioners? Our findings indicate
      that, in the setting of a rapid response system, there is a need to consider
      beyond the narrow interpretation of the NFR order, when a NFRRT may also be
      appropriate. This will require standardisation of such nomenclature, and training
      and education of those involved in documenting and interpreting such orders.
      Equally, it will require a different approach to the discussion with patients and
      their carers as to what the implications of an NFRRT order are. The findings also
      have significant implications as to the senior medical oversight of LMT, in
      particular for RRT, for whom it is their first encounter with such patients.
      Finally, the findings suggest that consideration be given to better delineating
      the documentation of the role of nursing staff when setting LMT orders.

PMID- 24589295
TI  - Magnetization reversal in asymmetric trilayer dots: effect of the interlayer
      magnetostatic coupling.
AB  - The spin structure and magnetization reversal in Co/insulator/Fe trilayer
      nanodots are investigated by micromagnetic simulations. The vortex and C-state
      are found and the magnetization reversal is dominated by the shape asymmetry of
      the dots, which is produced by cutting off a fraction of the circular dot. The
      vortex chirality is thus controlled by the magnetic field direction. On the other
      hand, the magnetostatic interaction between the top and bottom magnetic layers
      has interesting influence on the dot reversal process, where the
      magnetocrystalline anisotropy direction of the Co layer is allowed to vary within
      the layer plane. The combined effect of these two aspects is discussed on the
      base of dot coercivity, remanent magnetization, vortex nucleation and
      annihilation, and the bias of the Fe layer hysteresis loop. While leading to a
      new S-state in circle dots, the interlayer interaction facilitates the formation
      of C-state in asymmetric dots, which reduces the vortex nucleation field. The
      bias effect of all dots is decreased with the deviation of the Co layer easy axis
      from the field direction. Unlike the circle and semicircle dots, the field range
      of the vortex state in other asymmetric dots increases with the angle between the
      cutting direction and the Co layer anisotropy. Additionally, vortex ranges in
      less asymmetric dots even larger than that in the circle dots are evidenced
      unexpectedly. Therefore, the control of the vortex chirality and enhancement of
      the vortex range are found simultaneously. 

PMID- 24589294
TI  - Etravirine in treatment-experienced, HIV-1-infected children and adolescents: 48
      week safety, efficacy and resistance analysis of the phase II PIANO study.
AB  - OBJECTIVES: PIANO (Paediatric study of Intelence As an NNRTI Option; TMC125-C213;
      NCT00665847) assessed the safety/tolerability, antiviral activity and
      pharmacokinetics of etravirine plus an optimized background regimen (OBR) in
      treatment-experienced, HIV-1-infected children (>= 6 to < 12 years) and
      adolescents (>= 12 to < 18 years) over 48 weeks. METHODS: In a phase II, open
      label, single-arm study, 101 treatment-experienced patients (41 children; 60
      adolescents) with screening viral load (VL) >= 500 HIV-1 RNA copies/mL received
      etravirine 5.2 mg/kg (maximum dose 200 mg) twice a day (bid) plus OBR. RESULTS:
      Sixty-seven per cent of patients had previously used efavirenz or nevirapine. At
      week 48, the most common treatment-related grade >= 2 adverse event (AE) was rash
      (13%); 12% experienced grade 3 AEs. Only two grade 4 AEs occurred (both
      thrombocytopaenia, not etravirine related). At week 48, 56% of patients (68%
      children; 48% adolescents) achieved a virological response (VL<50 copies/mL;
      intent-to-treat, noncompleter=failure). Factors predictive of response were
      adherence > 95%, male sex, low baseline etravirine weighted genotypic score and
      high etravirine trough concentration (C0h ). Seventy-six patients (75%) completed
      the trial; most discontinuations occurred because of protocol noncompliance or
      AEs (8% each). Sixty-five per cent of patients were > 95% adherent by
      questionnaire and 39% by pill count. Forty-one patients experienced virological
      failure (VF; time-to-loss-of-virological-response non-VF-censored algorithm) (29
      nonresponders; 12 rebounders). Of 30 patients with VF with paired
      baseline/endpoint genotypes, 18 (60%) developed nonnucleoside reverse
      transcriptase inhibitor (NNRTI) mutations, most commonly Y181C. Mean etravirine
      area under the plasma concentration-time curve over 12 h (AUC0-12h ; 5216 ng
      h/mL) and C0h (346 ng/mL) were comparable to adult target values. CONCLUSIONS:
      Results with etravirine 5.2 mg/kg bid (with OBR) in this treatment-experienced
      paediatric population and etravirine 200 mg bid in treatment-experienced adults
      were comparable. Etravirine is an NNRTI option for treatment-experienced
      paediatric patients.

PMID- 24589296
TI  - Cluster and meta-analyses on factors influencing stress-induced alcohol drinking
      and relapse in rodents.
AB  - Numerous preclinical studies have focused on the identification of biological and
      environmental factors that modulate stress and alcohol interactions. Although
      there is a good qualitative description of the determinants of alcohol
      consumption in rodents, the magnitude of the variables influencing stress-induced
      ethanol intake and its dynamics are still poorly understood. We therefore carried
      out a clustered meta-analysis on stress-induced alcohol consumption in 1520 rats.
      Two-step clustering of the literature-derived dataset suggests a strong
      dependency of the experimental outcome on the method used to measure alcohol
      intake. Free-choice home cage drinking versus operant self-administration is the
      most critical determinant of stress-induced increases in alcohol consumption in
      rats. Stress does not typically result in enhanced alcohol consumption in operant
      self-administration paradigms, whereas it leads to increased home cage drinking.
      Stress-induced alcohol consumption is age dependent, with adults being more
      sensitive than adolescents. In addition, foot shock and forced swim stress
      enhance alcohol intake, while restraint stress does not. In contrast, a meta
      analysis of 327 rats on stress-induced reinstatement of alcohol-seeking behavior
      shows less influence of those modulating factors, and usually foot shock or
      yohimbine leads to a reinstatement of approximately 300 percent of extinction
      level responding. Via accurate characterization of the significant factors in the
      interplay of alcohol consumption, relapse and stress, our quantitative
      description not only improves the understanding of underlying mechanisms, but
      also provides an appropriate framework for the optimal experimental design of
      preclinical studies that more accurately translates to the human condition. 

PMID- 24589297
TI  - Relationship between working-memory network function and substance use: a 3-year
      longitudinal fMRI study in heavy cannabis users and controls.
AB  - Deficient executive functions play an important role in the development of
      addiction. Working-memory may therefore be a powerful predictor of the course of
      drug use, but chronic substance use may also impair working-memory. The aim of
      this 3-year longitudinal neuro-imaging study was to investigate the relationship
      between substance use (e.g. alcohol, cannabis, nicotine, illegal psychotropic
      drugs) and working-memory network function over time in heavy cannabis users and
      controls. Forty-nine participants performed an n-back working-memory task at
      baseline and at 3-year follow-up. At follow-up, there were 22 current heavy
      cannabis users, 4 abstinent heavy cannabis users and 23 non-cannabis-using
      controls. Tensor-independent component analysis (Tensor-ICA) was used to
      investigate individual differences in working-memory network functionality over
      time. Within the group of cannabis users, cannabis-related problems remained
      stable, whereas alcohol-related problems, nicotine dependence and illegal
      psychotropic substance use increased over time. At both measurements, behavioral
      performance and network functionality during the n-back task did not differ
      between heavy cannabis users and controls. Although n-back accuracy improved,
      working-memory network function remained stable over time. Within the group of
      cannabis users, working-memory network functionality was not associated with
      substance use. These results suggest that sustained moderate to heavy levels of
      cannabis, nicotine, alcohol and illegal psychotropic substance use do not change
      working-memory network functionality. Moreover, baseline network functionality
      did not predict cannabis use and related problems three years later, warranting
      longitudinal studies in more chronic or dependent cannabis users. 

PMID- 24589298
TI  - Liquid phase electron-beam-induced deposition on bulk substrates using
      environmental scanning electron microscopy.
AB  - The introduction of gases, such as water vapor, into an environmental scanning
      electron microscope is common practice to assist in the imaging of insulating or
      biological materials. However, this capability may also be exploited to
      introduce, or form, liquid phase precursors for electron-beam-induced deposition.
      In this work, the authors report the deposition of silver (Ag) and copper (Cu)
      structures using two different cell-less in situ deposition methods--the first
      involving the in situ hydration of solid precursors and the second involving the
      insertion of liquid droplets using a capillary style liquid injection system.
      Critically, the inclusion of surfactants is shown to drastically improve pattern
      replication without diminishing the purity of the metal deposits. Surfactants are
      estimated to reduce the droplet contact angle to below ~10 degrees .

PMID- 24589299
TI  - Photo-Fenton decomposition of beta-blockers atenolol and metoprolol; study and
      optimization of system parameters and identification of intermediates.
AB  - Active pharmaceutical compounds reach the wastewater treatment plants mainly
      through excretion and improper disposal, and, because of insufficient treating
      methods, they end up to surface water or even potable water in some cases.
      Atenolol and metoprolol are beta-blockers, members of cardiovascular
      pharmaceuticals group. They are generally used in the treatment of disorders such
      as hypertension, angina and arrhythmias. They have been in long-term use in
      Europe and North America, and they have also been detected in the aquatic
      environment. In this study the degradation of atenolol and metoprolol in aqueous
      solutions by means of the photo-Fenton reaction was investigated. The purpose of
      this study was: (i) to investigate the influence of the concentrations of iron
      and hydrogen peroxide, by means of central composite design, (ii) to study the
      degradation kinetics in aqueous solutions, (iii) to evaluate the mineralization
      and the toxicity evolution of the target compounds and (iv) to identify the
      degradation products. It has been found that increase of iron and hydrogen
      peroxide concentration accelerate the degradation of atenolol and metoprolol,
      while the kinetics of the process can be characterized as pseudo-first order. In
      general the photo-Fenton method has proved to be effective in decomposing and
      mineralizing the target compounds. The determination of the by-products formed
      during the degradation using LC-MS/MS equipment and the evaluation of the
      toxicity of the treated solution in different stages of the process would offer
      significant, innovative information regarding the treatment of water and
      wastewater containing active pharmaceutical compounds, especially of the beta
      blocker group. 

PMID- 24589300
TI  - Biodegradation of neonicotinoid insecticide, imidacloprid by restriction enzyme
      mediated integration (REMI) generated Trichoderma mutants.
AB  - REMI (restriction enzyme-mediated integration) technique was employed to
      construct Trichoderma atroviride strain T23 mutants with degrading capability of
      neonicotinoid insecticide, imidacloprid. The plasmid pBluescript II KS-hph used
      for integration in REMI mutants was confirmed by PCR and Southern hybridization.
      Among 153 transformants, 57% of them have showed higher neonicotinoid
      insecticide, imidacloprid, degradation ability than the wild strain T23 (p<0.01).
      More specifically, seven single-copied T. atroviride T23 transformants have
      confirmed a 30% higher degradation rate than their parent isolate. Among all
      transformed mutants, a 95% imidacloprid degradation rate was identified as the
      highest. This study, thus, provided an effective approach for improving
      neonicotinoid insecticide-degrading capability using REMI transformed T.
      atroviride mutants. 

PMID- 24589301
TI  - A novel protein distance matrix based on the minimum arc-length between two amino
      acid residues on the surface of a globular protein.
AB  - We present a novel protein distance matrix based on the minimum line of arc
      between two points on the surface of a protein. Two methods for calculating this
      distance matrix are developed and contrasted. The first method, which we have
      called TOPOL, is an approximate rule based algorithm consisting of successive
      rounds of vector addition. The second method is adapted from the graph theoretic
      approach of Dijkstra. Both procedures are demonstrated using cytochrome c, a
      12,500 Da protein, as a test case. In respect to computational speed and accuracy
      the TOPOL procedure compares favorably against the more complex method based on
      shortest path enumeration over a surface manifold grid. Some potential uses of
      the algorithmic approaches and calculated surface protein distance measurement
      are discussed.

PMID- 24589302
TI  - The hmp chemotaxis cluster regulates gliding in the filamentous cyanobacterium
      Nostoc punctiforme.
AB  - Many bacteria are capable of movement over surfaces without flagella or pili;
      they glide. Nostoc punctiforme is a cyanobacterium that differentiates
      specialized gliding filaments called hormogonia, but the mechanism underlying
      their movement is currently unknown. Risser et al. characterize the hormogonia
      motility and polysaccharide (hmp) locus that encodes proteins homologous to well
      studied chemotaxis systems. All but one of the genes in the locus were required
      for gliding motility and each protein localized as a ring near the cell junction.
      One protein, the CheA homologue HmpE, was capable of autophosphorylation and
      phosphotransfer to the CheY homologue HmpB. This study reveals the hmp locus as
      an important regulator of gliding and highlights N. punctiforme as a model for
      understanding gliding motility in a complex multicellular bacterium.

PMID- 24589306
TI  - Intracellular crystalline inclusions in a kidney transplant recipient.

PMID- 24589308
TI  - Colonization of Cimex lectularius with methicillin-resistant Staphylococcus
      aureus.
AB  - A recent paper published by Lowe and Romney in Emerging Infectious Diseases
      titled, Bed bugs as Vectors for Drug-Resistant Bacteria has sparked a renewed
      interest in bed bug vector potential. We followed a pyrethroid resistant strain
      of the human bed bug (Cimex lectularius, L.) fed either human blood or human
      blood with added methicillin resistant Staphylococcus aureus (MRSA) for 9 days
      post-feeding. Results indicated that while the bed bug midgut is a hospitable
      environment for MRSA, the bacteria does not survive longer than 9 days within the
      midgut. Additionally, MRSA is not amplified within the midgut of the bug as the
      infection was cleared within 9 days. Due to the weekly feeding behaviours of bed
      bugs, these results suggest that bed bug transmission of MRSA is highly unlikely.

PMID- 24589307
TI  - Treatment of gastric peritoneal carcinomatosis by combining complete surgical
      resection of lesions and intraperitoneal immunotherapy using catumaxomab.
AB  - BACKGROUND: The peritoneum is one of the most frequent sites of recurrent gastric
      carcinoma after curative treatment, despite the administration of pre- and/or
      postoperative systemic chemotherapy. Indeed, the prognosis of peritoneal
      carcinomatosis from gastric carcinoma continues to be poor, with a median
      survival of less than one year with systemic chemotherapy. Whereas the prognosis
      of peritoneal carcinomatosis from colorectal cancer has changed with the
      development of locally administered hyperthermic intraperitoneal chemotherapy
      (HIPEC), survival results following carcinomatosis from gastric cancer remain
      disappointing, yielding a 5-year survival rate of less than 20%. Innovative
      surgical therapies such as intraperitoneal immunotherapy therefore need to be
      developed for the immediate postoperative period after complete cytoreductive
      surgery. In a recent randomised study, a clinical effect was obtained after
      intraperitoneal infusion of catumaxomab in patients with malignant ascites,
      notably from gastric carcinoma. Catumaxomab, a nonhumanized chimeric antibody, is
      characterized by its unique ability to bind to three different types of cells:
      tumour cells expressing the epithelial cell adhesion molecule (EpCAM), T
      lymphocytes (CD3) and also accessory cells (Fcgamma receptor). Because the
      peritoneum is an immunocompetent organ and up to 90% of gastric carcinomas
      express EpCAM, intraperitoneal infusion of catumaxomab after complete resection
      of all macroscopic disease (as defined in the treatment of carcinomatosis from
      colorectal cancer) could therefore efficiently treat microscopic residual
      disease. METHODS/DESIGN: The aim of this randomized phase II study is to assess 2
      year overall survival after complete resection of limited carcinomatosis
      synchronous with gastric carcinoma, followed by an intraperitoneal infusion of
      catumaxomab with different total doses administered in each of the 2 arms. Close
      monitoring of peri-opertive mortality, morbidity and early surgical re
      intervention will be done with stopping rules. Besides this analysis,
      translational research will be conducted to determine immunological markers of
      catumaxomab efficacy and to correlate these markers with clinical efficacy.

PMID- 24589309
TI  - The timing of molecular and morphological changes underlying reproductive
      transitions in wild tomatoes (Solanum sect. Lycopersicon).
AB  - Molecular mechanisms underlying the transition from genetic self-incompatibility
      to self-compatibility are well documented, but the evolution of other
      reproductive trait changes that accompany shifts in reproductive strategy (mating
      system) remains comparatively under-investigated. A notable exception is the
      transition from exserted styles to styles with recessed positions relative to the
      anthers in wild tomatoes (Solanum Section Lycopersicon). This phenotypic change
      has been previously attributed to a specific mutation in the promoter of a gene
      that influences style length (style2.1); however, whether this specific
      regulatory mutation arose concurrently with the transition from long to short
      styles, and whether it is causally responsible for this phenotypic transition,
      has been poorly investigated across this group. To address this gap, we assessed
      74 accessions (populations) from 13 species for quantitative genetic variation in
      floral and reproductive traits as well as the presence/absence of deletions at
      two different locations (StyleD1 and StyleD2) within the regulatory region
      upstream of style2.1. We confirmed that the putatively causal deletion variant (a
      450-bp deletion at StyleD1) arose within self-compatible lineages. However, the
      variation and history of both StyleD1 and StyleD2 was more complex than
      previously inferred. In particular, although StyleD1 was statistically associated
      with differences in style length and stigma exsertion across all species, we
      found no evidence for this association within two species polymorphic for the
      StyleD1 mutation. We conclude that the previous association detected between
      phenotypic and molecular differences is most likely due to a phylogenetic
      association rather than a causal mechanistic relationship. Phenotypic variation
      in style length must therefore be due to other unexamined linked variants in the
      style2.1 regulatory region. 

PMID- 24589310
TI  - Dose reduction in whole-body computed tomography of multiple injuries (DoReMI):
      protocol for a prospective cohort study.
AB  - BACKGROUND: Single-pass, contrast-enhanced whole body multidetector computed
      tomography (MDCT) emerged as the diagnostic standard for evaluating patients with
      major trauma. Modern iterative image algorithms showed high image quality at a
      much lower radiation dose in the non-trauma setting. This study aims at
      investigating whether the radiation dose can safely be reduced in trauma patients
      without compromising the diagnostic accuracy and image quality. METHODS/DESIGN:
      Prospective observational study with two consecutive cohorts of patients.
      SETTING: A high-volume, academic, supra-regional trauma centre in Germany. STUDY
      POPULATION: Consecutive male and female patients who 1. had been exposed to a
      high-velocity trauma mechanism, 2. present with clinical evidence or high
      suspicion of multiple trauma (predicted Injury Severity Score [ISS] >=16) and 3.
      are scheduled for primary MDCT based on the decision of the trauma leader on
      call.Imaging protocols: In a before/after design, a consecutive series of 500
      patients will undergo single-pass, whole-body 128-row multi-detector computed
      tomography (MDCT) with a standard, as low as possible radiation dose. This will
      be followed by a consecutive series of 500 patients undergoing an approved ultra
      low dose MDCT protocol using an image processing algorithm. DATA: Routine
      administrative data and electronic patient records, as well as digital images
      stored in a picture archiving and communications system will serve as the primary
      data source. The protocol was approved by the institutional review board. MAIN
      OUTCOMES: (1) incidence of delayed diagnoses, (2) diagnostic accuracy, as
      correlated to the reference standard of a synopsis of all subsequent clinical,
      imaging, surgical and autopsy findings, (3) patients' safety, (4) radiation
      exposure (e.g. effective dose), (5) subjective image quality (assessed
      independently radiologists and trauma surgeons on a 100-mm visual analogue
      scale), (6) objective image quality (e.g., contrast-to-noise ratio). ANALYSIS:
      Multivariate regression will be employed to adjust and correct the findings for
      time and cohort effects. An exploratory interim analysis halfway after
      introduction of low-dose MDCT will be conducted to assess whether this protocol
      is clearly inferior or superior to the current standard. DISCUSSION: Although non
      experimental, this study will generate first large-scale data on the utility of
      imaging-enhancing algorithms in whole-body MDCT for major blunt trauma. TRIAL
      REGISTRATION: Current Controlled Trials ISRCTN74557102.

PMID- 24589311
TI  - New "missing link" genus of the colonial volvocine green algae gives insights
      into the evolution of oogamy.
AB  - BACKGROUND: The evolution of oogamy from isogamy, an important biological event,
      can be summarized as follows: morphologically similar gametes (isogametes)
      differentiated into small "male" and large "female" motile gametes during
      anisogamy, from which immotile female gametes (eggs) evolved. The volvocine green
      algae represent a model lineage to study this type of sex evolution and show two
      types of gametic unions: conjugation between isogametes outside the parental
      colonies (external fertilization during isogamy) and fertilization between small
      motile gametes (sperm) and large gametes (eggs) inside the female colony
      (internal fertilization during anisogamy and oogamy). Although recent cultural
      studies on volvocine algae revealed morphological diversity and molecular genetic
      data of sexual reproduction, an intermediate type of union between these two
      gametic unions has not been identified. RESULTS: We identified a novel colonial
      volvocine genus, Colemanosphaera, which produces bundles of spindle-shaped male
      gametes through successive divisions of colonial cells. Obligately anisogamous
      conjugation between male and female motile gametes occurred outside the female
      colony (external fertilization during anisogamy). This new genus contains 16- or
      32-celled spheroidal colonies similar to those of the volvocine genera
      Yamagishiella and Eudorina. However, Colemanosphaera can be clearly distinguished
      from these two genera based on its sister phylogenetic position to the enigmatic
      flattened colonial volvocine Platydorina and external fertilization during
      anisogamy. Two species of Colemanosphaera were found in a Japanese lake; these
      species are also distributed in European freshwaters based on a published
      sequence of an Austrian strain and the original description of Pandorina
      charkowiensis from Ukraine. CONCLUSIONS: Based on phylogeny and morphological
      data, this novel genus exhibits a missing link between Platydorina and the
      typical spheroidal colonial volvocine members such as Pandorina or Yamagishiella.
      Considering the external obligate anisogamy, oogamy evolution may have been
      preceded by the transition from external to internal fertilization during
      anisogamy within the volvocine green algae.

PMID- 24589312
TI  - Immunocompatibility and toxicity studies of poly-L-lysine nanocapsules in sprague
      dawley rats for drug-delivery applications.
AB  - Poly-L-Lysine (PLL) nanocapsules are the emerging drug-delivery vehicle for the
      therapeutics of targeted diseases. The study was designed for the synthesis and
      characterization of PLL nanocapsules and to know its immunocompatibility and
      toxicity behavior for in vivo drug-delivery applications. Alteration in
      hematologic parameters, immunomodulatory gene expression by RT-PCR studies,
      toxicity markers status, immunoblotting of major inflammatory marker proteins,
      and histopathologic studies from major tissues of rat after intravenous
      administration of PLL nanocapsules after 30 days were assessed. In vivo toxicity
      markers activity, hematologic parameters alteration, and RT-PCR analysis of
      important immunomodulatory genes such as monocyte chemotactic protein-1(MCP 1),
      tumor necrosis factor-alpha (TNF-alpha), Intercellular adhesion molecule-1 (ICAM
      1), and interleukin-6 (IL-6) showed least changes when compared with control. The
      immunoblotting of major inflammatory markers such as cyclooxygenase-2 (COX-2),
      lipo-oxygenase-15 (LOX-15), and nitric oxide synthase (NOS) found have least
      expression showing the immunocompatibility of PLL nanocapsules. Histopathologic
      studies of important tissues showed almost normal architecture after treatment
      using different concentration of PLL nanocapsules after the experimental period.
      The results showed a promising outcome and further confirmed the
      immunocompatibility and non-toxicity of PLL nanocapsules in vivo for drug
      delivery applications. 

PMID- 24589313
TI  - A serious parvovirus B19 genotype 2 infection not detected in a commercial PCR
      assay.

PMID- 24589314
TI  - Sore throat.
AB  - INTRODUCTION: About 10% of people present to primary healthcare services with
      sore throat each year. The causative organisms of sore throat may be bacteria
      (most commonly Streptococcus) or viruses (typically rhinovirus), although it is
      difficult to distinguish bacterial from viral infections clinically. METHODS AND
      OUTCOMES: We conducted a systematic review and aimed to answer the following
      clinical question: What are the effects of interventions to reduce symptoms of
      acute infective sore throat? We searched Medline, Embase, The Cochrane Library,
      and other important databases up to September 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 6 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:
      antibiotics, corticosteroids, non-steroidal anti-inflammatory drugs, and
      paracetamol.

PMID- 24589315
TI  - Stripes, dots and dali.

PMID- 24589316
TI  - Effect of cinacalcet treatment on vascular arterial stiffness among peritoneal
      dialysis patients with secondary hyperparathyroidism.
AB  - AIM: Although calcimimetics cinacalcet can reduce parathyroid hormone level and
      control secondary hyperparathyroidism in end-stage renal disease patients, risk
      of vascular calcification remains high. Whether cinacalcet can further reduce
      vascular damage or arterial stiffness is unknown. METHODS: We studied the effect
      of cinacalcet in 33 peritoneal dialysis patients with inadequately controlled
      secondary hyperparathyroidism despite standard treatment. The primary outcome was
      the aortic pulse wave velocity at 26 and 52 months after cinacalcet treatment.
      The pulse wave velocity was compared with that of a matched control cohort of 37
      peritoneal dialysis patients with secondary hyperparathyroidism. RESULTS: Thirty
      three patients completed the cinacalcet treatment, after median dialysis duration
      of 1.0 year. Significant improvement of parathyroid hormone level was achieved
      after 52 weeks, from 87.5 +/- 28.7 pmol/L to 34.5 +/- 45.5 pmol/L (P < 0.0001).
      Serial carotid-femoral pulse wave velocity did not differ between cinacalcet
      treatment group and control group (general linear model with repeated measures, P
      = 0.19). Among patients receiving cinacalcet, the average carotid-femoral pulse
      wave velocity increased from 10.46 +/- 2.12 m/s at baseline to 11.41 +/- 2.79 m/s
      at 52 weeks (P = 0.001). The change in carotid-femoral pulse wave velocity over 1
      year had no significant correlation with the final parathyroid hormone level or
      change in parathyroid hormone level. CONCLUSIONS: Among prevalent patients
      receiving peritoneal dialysis and with hyperparathyroidism, a reduction of 60.6%
      parathyroid hormone level after cinacalcet treatment for one year did not reduce
      the carotid-femoral pulse wave velocity.

PMID- 24589317
TI  - In-flight risk of venous thromboembolism and use of tranexamic acid in trauma
      patients.

PMID- 24589319
TI  - A 23-year-old woman with a ferrous sulfate overdose.

PMID- 24589321
TI  - Up all night.

PMID- 24589322
TI  - Therapeutic hypothermia, automated chest compressions, and death notification.

PMID- 24589323
TI  - Left behind: caring for children in families experiencing patient transport.

PMID- 24589324
TI  - Specialty pediatric transport in primary care or urgent care settings.
AB  - OBJECTIVE: We sought to describe a single center's experience with specialized
      critical care transport from non-hospital settings, including primary care
      offices and urgent care centers. We hypothesized that the majority of patients
      will require procedures outside the scope of practice of most EMS providers and
      will be better served by specialized pediatric critical care transport (SPCCT)
      teams. METHODS: This study sought to retrospectively evaluate instances where
      children (0-18 years old) were transported by our SPCCT team from nonhospital
      settings, including primary care offices and urgent care centers, in 2009 and
      2010. Data were extracted from a customized database and appropriate statistical
      tests were applied, including Fisher's exact test for categorical comparisons and
      Mann-Whitney U test for non-parametric data comparisons. RESULTS: Fifty-two
      patients were included. Most of the children were transported for respiratory
      distress (78%), and many were treated with albuterol (42%) and steroids (42%)
      prior to the SPCCT team arrival. The most common interventions performed by the
      SPCCT team were obtaining IV access and administering IV fluid boluses; 4 (7.7%)
      patients required advanced critical care treatments unique to SPCCT. Most
      patients (n = 34; 65%) were directly admitted to the general care floor, but a
      high number of patients (n = 12; 23%; PICU = 11, NICU = 1) required pediatric or
      neonatal intensive care unit admission. Only 3 patients (5.7%) were discharged
      home without hospital admission. For the 11 patients admitted to the PICU, the
      median length of stay (LOS) was 2.5 days (IQR 0.14-13.2). All patients survived
      to hospital discharge with an additional hospital LOS of 1.3 days (IQR 0.2-6.7).
      Patients were billed for these critical care transports an average of $2,660.14
      +/- $940. CONCLUSION: Our small cohort demonstrates infrequent application of
      advanced critical care interventions beyond those provided by the referring
      primary care office or urgent care centers. This supports the practice of SPCCT
      teams providing transport services for select critically ill children at primary
      care offices and urgent care centers, but not as a standard practice for most
      pediatric patients in these settings.

PMID- 24589325
TI  - Ketamine sedation during air medical retrieval of an agitated patient.
AB  - Air medical retrieval of acutely agitated patients is challenging in terms of
      safety for all parties involved. We describe a case in which the largest recorded
      dose of ketamine sedation in air medical history allowed the successful transport
      of an acutely agitated patient from a remote community. 

PMID- 24589326
TI  - The other side: a mother's story.

PMID- 24589328
TI  - Applications of the balanced scorecard for strategic management and performance
      measurement in the health sector.
AB  - In order to attain a useful balanced scorecard (BSC), appropriate performance
      perspectives and indicators are crucial to reflect all strategies of the
      organisation. The objectives of this survey were to give an insight regarding the
      situation of the BSC in the health sector over the past decade, and to afford a
      generic approach of the BSC development for health settings with specific focus
      on performance perspectives, performance indicators and BSC generation. After an
      extensive search based on publication date and research content, 29 articles
      published since 2002 were identified, categorised and analysed. Four critical
      attributes of each article were analysed, including BSC generation, performance
      perspectives, performance indicators and auxiliary tools. The results showed that
      'internal business process' was the most notable BSC perspective as it was
      included in all reviewed articles. After investigating the literature, it was
      concluded that its comprehensiveness is the reason for the importance and high
      usage of this perspective. The findings showed that 12 cases out of 29 reviewed
      articles (41%) exceeded the maximum number of key performance indicators (KPI)
      suggested in a previous study. It was found that all 12 cases were large
      organisations with numerous departments (e.g. national health organisations).
      Such organisations require numerous KPI to cover all of their strategic
      objectives. It was recommended to utilise the cascaded BSC within such
      organisations to avoid complexity and difficulty in gathering, analysing and
      interpreting performance data. Meanwhile it requires more medical staff to
      contribute in BSC development, which will result in greater reliability of the
      BSC. 

PMID- 24589329
TI  - Automated tests of ANA immunofluorescence as throughput autoantibody detection
      technology: strengths and limitations.
AB  - Anti-nuclear antibody (ANA) assay is a screening test used for almost all
      autoimmune rheumatic diseases, and in a number of these cases, it is a
      diagnostic/classification parameter. In addition, ANA is also a useful test for
      additional autoimmune disorders. The indirect immunofluorescence technique on
      monolayers of cultured epithelial cells is the current recommended method because
      it has higher sensitivity than solid phase assays. However, the technique is time
      consuming and requires skilled operators. Automated ANA reading systems have
      recently been developed, which offer the advantage of faster and much easier
      performance as well as better harmonization in the interpretation of the results.
      Preliminary validation studies of these systems have given promising results in
      terms of analytical specificity and reproducibility. However, these techniques
      require further validation in clinical studies and need improvement in their
      recognition of mixed or less common staining patterns. 

PMID- 24589330
TI  - Quantification of skeletal metastases in castrate-resistant prostate cancer
      predicts progression-free and overall survival.
AB  - OBJECTIVE: To report a simplified and effective method for substratification of
      M1 castrate-resistant prostate cancer (CRPC) by correlating progression-free
      (PFS) and overall survival (OS) with simple quantification of skeletal
      metastases. PATIENTS AND METHODS: In all, 561 men with M1 CRPC were studied
      longitudinally. Individual bone scan disease burden, quantified by counting bone
      metastasis number, was correlated with clinical outcome using specific threshold
      points of 1-4, 5-20 and >20 detectable lesions. RESULTS: Patients with a higher
      metastasis number had a shorter PFS and OS (hazard ratio [HR] 2.0, 95% confidence
      interval [CI] 1.7-2.4; P < 0.001). Patients with 1-4 metastases had much better
      PFS and OS than those with 5-20 metastases. The median PFS and OS in the latter
      was 10.9 (95% CI 8.4-12.8) and 22.1 (95% CI: 18.5-24.5) months, respectively. PFS
      and OS for patients with >20 metastases were shorter still [median 5.3 (95% CI
      3.4-6.9) months and 13.3 (95% CI 11.3-17.6) months, respectively]. Dichotomising
      into cohorts with 1-4 and >=5 metastases, the latter group had considerably
      poorer PFS [8.4 (95% CI 6.8-10.3) months; P < 0.001) and OS [18.7 (95% CI 17.5
      22.1) months; P < 0.001]. CONCLUSIONS: Dichotomising patients with CRPC into
      cohorts with 1-4 or >=5 skeletal metastases identifies a better and a worse
      cohort in a manner that is easy and clinically accessible. This simple method
      facilitates disease stratification and patient management, enabling clinicians to
      counsel patients more effectively about long-term outcomes and to help select
      intervention therapies more effectively.

PMID- 24589331
TI  - Reply to Jyotirmoy Das, Sudhir Kumar, Sangeeta Khanna, and Yatin Mehta's letter
      to the editor re: Mani Menon, Akshay Sood, Mahendra Bhandari, et al. Robotic
      kidney transplantation with regional hypothermia: a step-by-step description of
      the Vattikuti Urology Institute-Medanta Technique (IDEAL Phase 2a). Eur Urol
      2014;65:991-1000: robotic kidney transplantation: cool the kidney, warm the
      patient.

PMID- 24589332
TI  - Re: Mani Menon, Akshay Sood, Mahendra Bhandari, et al. Robotic kidney
      transplantation with regional hypothermia: a step-by-step description of the
      vAttikuti Urology Institute-Medanta Technique (IDEAL Phase 2a). Eur Urol
      2014;65:991-1000.

PMID- 24589333
TI  - Reported reasons for testing among hepatitis B virus-infected patients - Chronic
      Hepatitis Cohort Study (CHeCS), United States, 2006-2010.

PMID- 24589335
TI  - Interventions to improve cultural competency in healthcare: a systematic review
      of reviews.
AB  - BACKGROUND: Cultural competency is a recognized and popular approach to improving
      the provision of health care to racial/ethnic minority groups in the community
      with the aim of reducing racial/ethnic health disparities. The aim of this
      systematic review of reviews is to gather and synthesize existing reviews of
      studies in the field to form a comprehensive understanding of the current
      evidence base that can guide future interventions and research in the area.
      METHODS: A systematic review of review articles published between January 2000
      and June 2012 was conducted. Electronic databases (including Medline, Cinahl and
      PsycINFO), reference lists of articles, and key websites were searched. Reviews
      of cultural competency in health settings only were included. Each review was
      critically appraised by two authors using a study appraisal tool and were given a
      quality assessment rating of weak, moderate or strong. RESULTS: Nineteen
      published reviews were identified. Reviews consisted of between 5 and 38 studies,
      included a variety of health care settings/contexts and a range of study types.
      There were three main categories of study outcomes: patient-related outcomes,
      provider-related outcomes, and health service access and utilization outcomes.
      The majority of reviews found moderate evidence of improvement in provider
      outcomes and health care access and utilization outcomes but weaker evidence for
      improvements in patient/client outcomes. CONCLUSION: This review of reviews
      indicates that there is some evidence that interventions to improve cultural
      competency can improve patient/client health outcomes. However, a lack of
      methodological rigor is common amongst the studies included in reviews and many
      of the studies rely on self-report, which is subject to a range of biases, while
      objective evidence of intervention effectiveness was rare. Future research should
      measure both healthcare provider and patient/client health outcomes, consider
      organizational factors, and utilize more rigorous study designs.

PMID- 24589337
TI  - Activated neutrophils induce epithelial cell apoptosis through oxidant-dependent
      tyrosine dephosphorylation of caspase-8.
AB  - Activated neutrophils can injure host cells through direct effects of oxidants on
      membrane phospholipids, but an ability to induce apoptotic cell death has not
      previously been reported. We show that neutrophils activated in vivo in patients
      who have sustained multiple trauma or in vitro by exposure to bacterial
      lipopolysaccharide promote epithelial cell apoptosis through SHP-1-mediated
      dephosphorylation of epithelial cell caspase-8. Epithelial cell apoptosis induced
      by circulating neutrophils from patients who had sustained serious injury
      depended on the generation of neutrophil-derived reactive oxygen intermediates
      and was blocked by inhibition of NADPH oxidase or restoration of intracellular
      glutathione. Caspase-8 was constitutively tyrosine phosphorylated in a panel of
      resting epithelial cells, but underwent SHP-1-dependent dephosphorylation in
      response to hydrogen peroxide, activated neutrophils, or inhibition of Src
      kinases. Cells transfected with a mutant caspase-8 in which tyrosine residues at
      Tyr397 or Tyr465 are replaced by nonphosphorylatable phenylalanine underwent
      accelerated apoptosis, whereas either mutation of these residues to
      phosphomimetic glutamic acid or transfection with the Src kinases Lyn or c-Src
      inhibited hydrogen peroxide-induced apoptosis. Exposure to either hydrogen
      peroxide or lipopolysaccharide-stimulated neutrophils increased phosphorylation
      and activity of the phosphatase SHP-1, increased activity of caspases 8 and 3,
      and accelerated epithelial cell apoptosis. These observations reveal a novel
      mechanism for neutrophil-mediated tissue injury through oxidant-dependent, SHP-1
      mediated dephosphorylation of caspase-8 resulting in enhanced epithelial cell
      apoptosis.

PMID- 24589339
TI  - Protein profiling of Helicobacter pylori-associated gastric cancer.
AB  - Helicobacter pylori infection is an initiating factor in the development of
      gastric cancer. Gastric cancer can be divided into two groups on the basis of H.
      pylori serological status; seropositive H. pylori status predicts favorable
      prognosis in patients with gastric cancer. By using the protein pathway array, we
      identified 20 differentially expressed proteins in primary gastric cancer tissues
      between the H. pylori-seropositive and H. pylori-seronegative groups. Our results
      indicate that both brassinosteroid insensitive 1-associated kinase 1 and
      calpastatin are favorable prognostic factors in H. pylori-seropositive gastric
      cancer patients. In contrast, dachshund homolog 1 is a favorable prognostic
      factor in H. pylori-seronegative gastric cancer patients. Different signaling
      pathways were found to be altered between H. pylori-seropositive and H. pylori
      seronegative gastric cancer, which may account for the different tumorigenesis
      and outcomes between these two subsets of patients. 

PMID- 24589338
TI  - CD133-targeted niche-dependent therapy in cancer: a multipronged approach.
AB  - Cancer treatment continues to be challenged by the development of therapeutic
      resistances and relapses in the clinical setting, which are largely attributed to
      tumor heterogeneity, particularly the existence of cancer stem cells (CSCs).
      Thus, targeting the CSC subpopulation may represent an effective therapeutic
      strategy. However, despite advances in identifying and characterizing CD133(+)
      CSCs in various human cancers, efforts to translate these experimental findings
      to clinical modalities have been slow in the making, especially in light of the
      growing awareness of CSC plasticity and the foreseeable pitfall of
      therapeutically targeting CSC base sorely on a surface marker. We, and others,
      have demonstrated that the CD133(+) CSCs reside in complex vascular niches, where
      reciprocal signaling between the CD133(+) CSCs and their microenvironment may
      govern niche morphogenesis and homeostasis. Herein, we discuss the multifaceted
      functional role of the CD133(+) cells in the context of their niche, and the
      potential of targeting CD133 as a niche-dependent approach in effective therapy. 

PMID- 24589340
TI  - Penetrating ocular trauma associated with blank cartridge.
AB  - BACKGROUND: Blank cartridge guns are generally regarded as being harmless and
      relative safe. However recent published articles demonstrated that the gas
      pressure from the exploding propellant of blank cartridge is powerful enough to
      penetrate the thoracic wall, abdominal muscle, small intestine and the skull. And
      there has been a limited number of case reports of ocular trauma associated with
      blank cartridge injury. In addition, no report on case with split extraocular
      muscle injury with traumatic cataract and penetrating corneoscleral wound
      associated with blank cartridge has been previously documented. This report
      describes the case of patient who sustained penetrating ocular injury with
      extraocular muscle injury by a close-distance blank cartridge that required
      surgical intervention. CASE PRESENTATION: A 20-year-old man sustained a
      penetrating globe injury in the right eye while cleaning a blank cartridge
      pistol. His uncorrected visual acuity at presentation was hand motion and he had
      a flame burn of his right upper and lower lid with multiple missile wounds. On
      slit-lamp examination, there was a 12-mm laceration of conjunctiva along the 9
      o'clock position with two pinhole-like penetrating injuries of cornea and sclera.
      There was also a 3-mm corneal laceration between 9 o'clock and 12 o'clock and the
      exposed lateral rectus muscle was split. Severe Descemet's membrane folding with
      stromal edema was observed, and numerous yellow, powder-like foreign bodies were
      impacted in the cornea. Layered anterior chamber bleeding with traumatic cataract
      was also noted. Transverse view of ultrasonography showed hyperechoic foreign
      bodies with mild reduplication echoes and shadowing. However, a computed
      tomographic scan using thin section did not reveal a radiopaque foreign body
      within the right globe. CONCLUSION: To our best knowledge, this is the first case
      report of split extraocular muscle injury with traumatic cataract and penetrating
      ocular injury caused by blank cartridge injury. Intraocular foreign bodies
      undetectable by CT were identified by B-scan ultrasonography in our patient. This
      case highlights the importance of additional ultrasonography when evaluating
      severe ocular trauma. And ophthalmologists should consider the possibility of
      penetrating injury caused by blank ammunition.

PMID- 24589341
TI  - Autosomal recessive phosphoglucomutase 3 (PGM3) mutations link glycosylation
      defects to atopy, immune deficiency, autoimmunity, and neurocognitive impairment.
AB  - BACKGROUND: Identifying genetic syndromes that lead to significant atopic disease
      can open new pathways for investigation and intervention in allergy. OBJECTIVE:
      We sought to define a genetic syndrome of severe atopy, increased serum IgE
      levels, immune deficiency, autoimmunity, and motor and neurocognitive impairment.
      METHODS: Eight patients from 2 families with similar syndromic features were
      studied. Thorough clinical evaluations, including brain magnetic resonance
      imaging and sensory evoked potentials, were performed. Peripheral lymphocyte flow
      cytometry, antibody responses, and T-cell cytokine production were measured.
      Whole-exome sequencing was performed to identify disease-causing mutations.
      Immunoblotting, quantitative RT-PCR, enzymatic assays, nucleotide sugar, and
      sugar phosphate analyses, along with matrix-assisted laser desorption/ionization
      time-of-flight mass spectrometry of glycans, were used to determine the molecular
      consequences of the mutations. RESULTS: Marked atopy and autoimmunity were
      associated with increased T(H)2 and T(H)17 cytokine production by CD4(+) T cells.
      Bacterial and viral infection susceptibility were noted along with T-cell
      lymphopenia, particularly of CD8(+) T cells, and reduced memory B-cell numbers.
      Apparent brain hypomyelination resulted in markedly delayed evoked potentials and
      likely contributed to neurologic abnormalities. Disease segregated with novel
      autosomal recessive mutations in a single gene, phosphoglucomutase 3 (PGM3).
      Although PGM3 protein expression was variably diminished, impaired function was
      demonstrated by decreased enzyme activity and reduced uridine diphosphate-N
      acetyl-D-glucosamine, along with decreased O- and N-linked protein glycosylation
      in patients' cells. These results define a new congenital disorder of
      glycosylation. CONCLUSIONS: Autosomal recessive hypomorphic PGM3 mutations
      underlie a disorder of severe atopy, immune deficiency, autoimmunity,
      intellectual disability, and hypomyelination.

PMID- 24589343
TI  - Nasal filters for the treatment of allergic rhinitis: a randomized, double-blind,
      placebo-controlled crossover clinical trial.

PMID- 24589342
TI  - Advances in basic and clinical immunology in 2013.
AB  - A significant number of contributions to our understanding of primary
      immunodeficiencies (PIDs) in pathogenesis, diagnosis, and treatment were
      published in the Journal in 2013. For example, deficiency of mast cell
      degranulation caused by signal transducer and activator of transcription 3
      deficiency was demonstrated to contribute to the difference in the frequency of
      severe allergic reactions in patients with autosomal dominant hyper-IgE syndrome
      compared with that seen in atopic subjects with similar high IgE serum levels.
      High levels of nonglycosylated IgA were found in patients with Wiskott-Aldrich
      syndrome, and these abnormal antibodies might contribute to the nephropathy seen
      in these patients. New described genes causing immunodeficiency included caspase
      recruitment domain 11 (CARD11), mucosa-associated lymphoid tissue 1 (MALT1) for
      combined immunodeficiencies, and tetratricopeptide repeat domain 7A (TTC7A) for
      mutations associated with multiple atresia with combined immunodeficiency. Other
      observations expand the spectrum of clinical presentation of specific gene
      defects (eg, adult-onset idiopathic T-cell lymphopenia and early-onset
      autoimmunity might be due to hypomorphic mutations of the recombination
      activating genes). Newborn screening in California established the incidence of
      severe combined immunodeficiency at 1 in 66,250 live births. The use of
      hematopoietic stem cell transplantation for PIDs was reviewed, with
      recommendations to give priority to research oriented to establish the best
      regimens to improve the safety and efficacy of bone marrow transplantation. These
      represent only a fraction of significant research done in patients with PIDs that
      has accelerated the quality of care of these patients. Genetic analysis of
      patients has demonstrated multiple phenotypic expressions of immune deficiency in
      patients with nearly identical genotypes, suggesting that additional genetic
      factors, possibly gene dosage, or environmental factors are responsible for this
      diversity.

PMID- 24589346
TI  - Are opioid antagonists effective in attenuating the core symptoms of autism
      spectrum conditions in children: a systematic review.
AB  - BACKGROUND: ASC (autism spectrum conditions) may result from a failure of
      striatal beta endorphins to diminish with maturation. Many symptoms of ASC
      resemble behaviours induced in animals or humans by opiate administration,
      including decreased socialisation, diminished crying, repetitive stereotypies,
      insensitivity to pain and motor hyperactivity. Naltrexone, an opioid antagonist,
      has been used in the management of children with ASC and can produce a clinically
      significant reduction in the serious and life-threatening behaviour of self
      injury for individuals who have not been responsive to any other type of
      treatment and is important for this reason. It was therefore appropriate to
      reconsider the available evidence and a systematic review was undertaken.
      METHODS: Four electronic databases were searched for relevant journal articles.
      In addition, cross-referencing of pertinent reviews and a hand search for
      articles in major international intellectual disability (ID) journals between the
      years 2010 and 2012 was carried out to ensure that all relevant articles were
      identified. We also searched databases for unpublished clinical trials to
      overcome publication bias. Each database was searched up to present (February
      2013) with no restrictions on the date of publication. The search terms consisted
      of broad expressions used to describe ID and autistic spectrum disorder as well
      as terms relating to opioid antagonists and specific drugs. All studies
      identified by the electronic database search and hand search were examined on the
      basis of title alone for relevance and duplication. The abstracts of the
      remaining papers were then scrutinised against the inclusion criteria. Where
      abstracts failed to provide adequate information, the full texts for these papers
      were obtained. All the full texts were then evaluated against the inclusion
      proforma. Two reviewers carried out all the stages of the process independently.
      The reviewers met to discuss their selections and where disagreements arose,
      these were settled by discussion with a member of the study group. Data from each
      study meeting the inclusion criteria were extracted on a pre-piloted data
      extraction form. The quality of each study was further assessed using the Jadad
      scale, a tool developed to assess the quality of randomised controlled trials.
      RESULTS: 155 children participated in 10 studies; 27 received placebo. Of the 128
      that received naltrexone 98 (77%) showed statistically significant improvement in
      symptoms of irritability and hyperactivity. Side effects were mild and the drug
      was generally well tolerated. CONCLUSIONS: Naltrexone may improve hyperactivity
      and restlessness in children with autism but there was not sufficient evidence
      that it had an impact on core features of autism in majority of the participants.
      It is likely that a subgroup of children with autism and abnormal endorphin
      levels may respond to naltrexone and identifying the characteristics of these
      children must become a priority.

PMID- 24589345
TI  - Interleukin-6 as inflammatory marker referring to multiple organ dysfunction
      syndrome in severely injured children.
AB  - BACKGROUND: Despite the suggestion that the inflammatory response in traumatized
      children is functionally unique, prognostic markers predicting pediatric multiple
      organ failure are lacking. We intended to verify whether Interleukin-6 (IL-6)
      displays a pivotal role in pediatric trauma similar to adults. METHODS:
      Traumatized children less than 18 years of age with an Injury Severity Score >9
      points and consecutive admission to the hospital's pediatric intensive care unit
      were included. Organ function was evaluated according to the score by Marshall et
      al. while IL-6 levels were measured repetitively every morning. RESULTS: 59
      traumatized children were included (8.4 +/- 4.4 years; 57.6% male gender).
      Incidence of MODS was 11.9%. No differences were found referring to age, gender,
      injury distribution or overall injury severity between children with and without
      MODS. Increased IL-6 levels during hospital admission were associated with injury
      severity (Spearman correlation: r = 0.522, p < 0.001), while an inconsistent
      association towards the development of MODS was proven at that time point
      (Spearman correlation: r = 0.180, p = 0.231; Pearson's correlation: r = 0.297, p
      = 0.045). However, increased IL-6 levels during the first two days were no longer
      associated with the injury severity but a significant correlation to MODS was
      measured. CONCLUSIONS: The presented prospective study is the first providing
      evidence for a correlation of IL-6 levels with injury severity and the incidence
      of MODS in traumatized children.

PMID- 24589344
TI  - Unsupervised phenotyping of Severe Asthma Research Program participants using
      expanded lung data.
AB  - BACKGROUND: Previous studies have identified asthma phenotypes based on small
      numbers of clinical, physiologic, or inflammatory characteristics. However, no
      studies have used a wide range of variables using machine learning approaches.
      OBJECTIVES: We sought to identify subphenotypes of asthma by using blood,
      bronchoscopic, exhaled nitric oxide, and clinical data from the Severe Asthma
      Research Program with unsupervised clustering and then characterize them by using
      supervised learning approaches. METHODS: Unsupervised clustering approaches were
      applied to 112 clinical, physiologic, and inflammatory variables from 378
      subjects. Variable selection and supervised learning techniques were used to
      select relevant and nonredundant variables and address their predictive values,
      as well as the predictive value of the full variable set. RESULTS: Ten variable
      clusters and 6 subject clusters were identified, which differed and overlapped
      with previous clusters. Patients with traditionally defined severe asthma were
      distributed through subject clusters 3 to 6. Cluster 4 identified patients with
      early-onset allergic asthma with low lung function and eosinophilic inflammation.
      Patients with later-onset, mostly severe asthma with nasal polyps and
      eosinophilia characterized cluster 5. Cluster 6 asthmatic patients manifested
      persistent inflammation in blood and bronchoalveolar lavage fluid and
      exacerbations despite high systemic corticosteroid use and side effects. Age of
      asthma onset, quality of life, symptoms, medications, and health care use were
      some of the 51 nonredundant variables distinguishing subject clusters. These 51
      variables classified test cases with 88% accuracy compared with 93% accuracy with
      all 112 variables. CONCLUSION: The unsupervised machine learning approaches used
      here provide unique insights into disease, confirming other approaches while
      revealing novel additional phenotypes.

PMID- 24589348
TI  - If a tree doesn't fall in a forest ... ?

PMID- 24589347
TI  - Variability of magnetoencephalographic sensor sensitivity measures as a function
      of age, brain volume and cortical area.
AB  - OBJECTIVE: To assess the feasibility and appropriateness of
      magnetoencephalography (MEG) for both adult and pediatric studies, as well as for
      the developmental comparison of these factors across a wide range of ages.
      METHODS: For 45 subjects with ages from 1 to 24years (infants, toddlers, school
      age children and young adults), lead fields (LFs) of MEG sensors are computed
      using anatomically realistic boundary element models (BEMs) and individually
      reconstructed cortical surfaces. Novel metrics are introduced to quantify MEG
      sensor focality. RESULTS: The variability of MEG focality is graphed as a
      function of brain volume and cortical area. Statistically significant differences
      in total cerebral volume, cortical area, MEG global sensitivity and LF focality
      are found between age groups. CONCLUSIONS: Because MEG focality and sensitivity
      differ substantially across the age groups studied, the cortical LF maps explored
      here can provide important insights for the examination and interpretation of MEG
      signals from early childhood to young adulthood. SIGNIFICANCE: This is the first
      study to (1) investigate the relationship between MEG cortical LFs and brain
      volume as well as cortical area across development, and (2) compare LFs between
      subjects with different head sizes using detailed cortical reconstructions.

PMID- 24589349
TI  - Modulation of visual evoked potentials by high-frequency repetitive transcranial
      magnetic stimulation in migraineurs.
AB  - OBJECTIVE: High-frequency repetitive transcranial magnetic stimulation (rTMS)
      modulates cortical excitability. We investigated its effect on visual evoked
      potentials (VEPs) in migraine. METHODS: Thirty-two headache-free controls (CO),
      25 interictal (MINT) and 7 preictal migraineurs (MPRE) remained after exclusions.
      VEPs to 8' and 65' checks were averaged in six blocks of 100 single responses.
      VEPs were recorded before, directly after and 25min after 10Hz rTMS. The study
      was blinded for diagnosis during recording and for diagnosis and block number
      during analysis. First block amplitudes and habituation (linear amplitude change
      over blocks) were analysed with repeated measures ANOVA. RESULTS: With 65'
      checks, N70-P100 habituation was reduced in MINT compared to CO after rTMS
      (p=0.013). With 8' checks, habituation was reduced in MPRE compared to MINT and
      CO after rTMS (p<0.016). No effects of rTMS on first block amplitudes were found.
      CONCLUSION: RTMS reduced habituation only in migraineurs, indicating increased
      responsivity to rTMS. The magnocellular visual subsystem may be affected
      interictally, while the parvocellular system may only be affected preictally.
      SIGNIFICANCE: Migraineurs may have increased responsiveness to rTMS because of a
      cortical dysfunction that changes before a migraine attack.

PMID- 24589351
TI  - [Acute care of critically ill children in general hospitals: organisation and
      training].
AB  - OBJECTIVE: To gain insight into how the acute care of critically ill children at
      general hospitals is organised, whether staff is sufficiently trained and whether
      the necessary materials and medications are present. DESIGN: Questionnaire
      combined with a site visit. METHOD: Questionnaires were sent to all primarily
      involved specialists (emergency room specialists and paediatricians), and to the
      auxiliary anaesthetists and intensivists involved, at the nine general hospitals
      in Southeast Netherlands. Two researchers performed standardised interviews with
      the lead paediatricians on site and checked for materials and medication present
      in the emergency and paediatric departments. RESULTS: Of the 195 questionnaires
      sent, 97 (49.7%) were deemed suitable for analysis. The response from the primary
      specialists involved (77.6%) was more than twice that of the auxiliary
      specialists (31.9%). At 7 hospitals, verbal agreements on the organisation of
      acute care were maintained, 1 hospital had a written protocol, and 2 hospitals
      had a task force addressing this topic. One out of 5 respondents was unaware of
      the verbal agreements and 1 out of 3 mistakenly assumed that a protocol existed.
      Two out of 3 primary specialists involved were certified for Advanced Paediatric
      Life Support (APLS); 1 out of 13 of the auxiliary specialists had such a
      certificate. Scenario training was being conducted at 8 hospitals. A paediatric
      resuscitation cart was available at both the emergency and paediatric departments
      of 8 hospitals, 3 of which were fully stocked at both departments. Laryngeal mask
      airways and PEEP-valves (Positive End Expiratory Pressure) were lacking at 6 of
      the 9 hospitals. The medication stock was complete at all the hospitals.
      CONCLUSION: The organisation of and training for the acute care of critically ill
      children and presence of materials - the aspects we investigated - need attention
      at all general hospitals evaluated. It appeared that many specialists are not
      APLS certified and written protocols concerning organisation and training were
      lacking. The establishment of a task force responsible for the acute care of
      children is one measure that could result in rapid improvement. Another measure
      could be the introduction of a standardised list of inventory needed for acute
      care.

PMID- 24589350
TI  - Genetically distinct pathways guide effector export through the type VI secretion
      system.
AB  - Bacterial secretion systems often employ molecular chaperones to recognize and
      facilitate export of their substrates. Recent work demonstrated that a secreted
      component of the type VI secretion system (T6SS), haemolysin co-regulated protein
      (Hcp), binds directly to effectors, enhancing their stability in the bacterial
      cytoplasm. Herein, we describe a quantitative cellular proteomics screen for T6S
      substrates that exploits this chaperone-like quality of Hcp. Application of this
      approach to the Hcp secretion island I-encoded T6SS (H1-T6SS) of Pseudomonas
      aeruginosa led to the identification of a novel effector protein, termed Tse4
      (type VI secretion exported 4), subsequently shown to act as a potent intra
      specific H1-T6SS-delivered antibacterial toxin. Interestingly, our screen failed
      to identify two predicted H1-T6SS effectors, Tse5 and Tse6, which differ from Hcp
      stabilized substrates by the presence of toxin-associated PAAR-repeat motifs and
      genetic linkage to members of the valine-glycine repeat protein G (vgrG) genes.
      Genetic studies further distinguished these two groups of effectors: Hcp
      stabilized effectors were found to display redundancy in interbacterial
      competition with respect to the requirement for the two H1-T6SS-exported VgrG
      proteins, whereas Tse5 and Tse6 delivery strictly required a cognate VgrG.
      Together, we propose that interaction with either VgrG or Hcp defines distinct
      pathways for T6S effector export. 

PMID- 24589352
TI  - Provider and staff perceptions of veterans' attrition from a national primary
      care weight management program.
AB  - BACKGROUND: Overweight and obesity are growing problems for primary care.
      Although effective weight management programs exist, these programs experience
      significant attrition, which limits effectiveness. OBJECTIVES: This study
      examined provider and staff perceptions of attrition from the Veterans Health
      Administration MOVE!((r)) Weight Management Program as an initial step toward
      understanding attrition from primary care-based programs. PARTICIPANTS:
      MOVE!((r)) clinicians, primary care providers, and other staff members who
      interacted with patients about participating in MOVE!((r)) (n=754) from
      Department of Veterans Affairs medical centers throughout the United States.
      Respondents were predominantly female (80.8%), Caucasian (79.2%), and trained as
      nurses (L.P.N., R.N., or N.P.; 50%). MEASURE: Participants completed a web
      mediated survey; items assessed agreement with personal and programmatic reasons
      for dropout, and allowed respondents to indicate the number one reason for
      dropout in an open-ended format. This survey was adapted from an existing tool
      designed to capture patient perceptions. RESULTS: Respondents indicated that
      veterans experienced practical barriers to attendance (eg, transportation and
      scheduling difficulties) and desire for additions to the program (eg, a live
      exercise component). Low motivation was the primary factor identified by
      respondents as associated with dropout, particularly as noted by MOVE!((r))
      clinicians (versus other providers/staff; P<0.01). CONCLUSIONS: These findings
      suggest that programmatic changes, such as adding additional meeting times or in
      session exercise time, may be of benefit to MOVE!((r)). In addition, increasing
      the use of techniques such as Motivational Interviewing among providers who refer
      patients to MOVE!((r)) may improve participant engagement in MOVE!((r)) and other
      primary care-based weight management programs. Further research is needed to
      effectively identify those likely to withdraw from weight management programs
      before achieving their goals, and the reasons for withdrawal.

PMID- 24589353
TI  - A new subfamily LIP of the major intrinsic proteins.
AB  - BACKGROUND: Proteins of the major intrinsic protein (MIP) family, or aquaporins,
      have been detected in almost all organisms. These proteins are important in cells
      and organisms because they allow for passive transmembrane transport of water and
      other small, uncharged polar molecules. RESULTS: We compared the predicted amino
      acid sequences of 20 MIPs from several algae species of the phylum
      Heterokontophyta (Kingdom Chromista) with the sequences of MIPs from other
      organisms. Multiple sequence alignments revealed motifs that were homologous to
      functionally important NPA motifs and the so-called ar/R-selective filter of
      glyceroporins and aquaporins. The MIP sequences of the studied chromists fell
      into several clusters that belonged to different groups of MIPs from a wide
      variety of organisms from different Kingdoms. Two of these proteins belong to
      Plasma membrane intrinsic proteins (PIPs), four of them belong to GlpF-like
      intrinsic proteins (GIPs), and one of them belongs to a specific MIPE subfamily
      from green algae. Three proteins belong to the unclassified MIPs, two of which
      are of bacterial origin. Eight of the studied MIPs contain an NPM-motif in place
      of the second conserved NPA-motif typical of the majority of MIPs. The MIPs of
      heterokonts within all detected clusters can differ from other MIPs in the same
      cluster regarding the structure of the ar/R-selective filter and other generally
      conserved motifs. CONCLUSIONS: We proposed placing nine MIPs from heterokonts
      into a new group, which we have named the LIPs (large intrinsic proteins). The
      possible substrate specificities of the studied MIPs are discussed.

PMID- 24589354
TI  - Histopathological characteristics of human non-tumor thyroid tissues in a long
      term model of adenomatous goiter xenografts in the NOD/Shi-scid, IL-2Rgamma(null)
      mouse.
AB  - There is a growing need for modeling the human thyroid to link data obtained from
      animals to humans because of its sensitivity to radiation exposure and endocrine
      disruption chemicals. In a scid mouse model produced by transplanting human
      thyroid tissues, leakiness and thymic lymphoma that occurs spontaneously in the
      scid mouse can complicate the interpretation of experimental results. Considering
      that the NOD.Cg-Prkdc(scid)Il2rg(tm1Sug)/Jic mouse (NOD/Shi-scid, IL
      2Rgamma(null) or NOG mouse) may be a better host because this strain has low
      incidence of leakiness and thymic lymphoma, we have evaluated the potential of a
      model that allows long-term observation of non-tumor human thyroid tissues in
      this mouse. We transplanted tissues of human adenomatous goiter into NOG mice and
      examined the tissues histopathologically. The morphology of human adenomatous
      goiter tissues was maintained from 24 to 44 weeks after transplantation in NOG
      mice with no noted differences between donor-matched tissues or the weeks after
      transplantation. The tissues expressed thyroglobulin protein and mRNA as well as
      thyroperoxidase. Endothelial cells originating from human were found in the
      transplanted tissues and were thought to be a characteristic of this model. The
      intactness of the tissues before transplantation was found to affect the rate of
      tissue engraftment. From the present results we have concluded that transplanted
      thyroid tissues in NOG mice maintain the histopathological characteristics of
      their origin for long terms. Therefore this model was thought feasible for
      toxicity evaluation. 

PMID- 24589355
TI  - New force field on modeling intrinsically disordered proteins.
AB  - Intrinsically disordered proteins or intrinsically disordered protein regions
      comprise a large portion of eukaryotic proteomes (between 35% and 51%). These
      intrinsically disordered proteins were found to link with cancer and various
      other diseases. However, widely used additive force field parameter sets are
      insufficient in quantifying the structural properties of intrinsically disordered
      proteins. Therefore, we explored to a systematic correction of a base additive
      force field parameter set (chosen as Amber ff99SBildn) to correct the biases that
      was first demonstrated in simulations with the base parameter set. Specifically,
      the phi/psi distributions of disorder-promoting residues were systematically
      corrected with the CMAP method. Our simulations show that the CMAP corrected
      Amber parameter set, termed ff99IDPs, improves the phi/psi distributions of the
      disorder-promoting residues with respect to the benchmark data of intrinsically
      disordered protein structures, with root mean-squared percentage deviation less
      than 0.15% between the simulation and the benchmark. Our further validation shows
      that the chemical shifts from the ff99IDPs simulations are in quantitative
      agreement with those from reported NMR measurements for two tested IDPs, MeV
      NTAIL , and p53. The predicted residue dipolar couplings also show high
      correlation with experimental data. Interestingly, our simulations show that
      ff99IDPs can still be used to model the ordered state when the intrinsically
      disordered proteins are in complex, in contrast to ff99SBildn that can be applied
      well only to the ordered complex structures. These findings confirm that the
      newly proposed Amber ff99IDPs parameter set provides a reasonable tool in further
      studies of intrinsically disordered protein structures. In addition, our study
      also shows the importance of considering intrinsically disordered protein
      structures in general-purposed force field developments for both additive and non
      additive models. 

PMID- 24589356
TI  - Association between genes, stressful childhood events and processing bias in
      depression vulnerable individuals.
AB  - The brain-derived neurotrophic factor (BDNF) and catechol-O-methyltransferase
      (COMT) genes are relevant candidates for depression. Variation in these genes is
      associated with stress sensitivity and depressotypic cognitive biases. The
      interaction between genes and stressful events is considered as an important
      mechanism in the development of depression. This study examined the effects of
      the BDNF and COMT genes on biased processing and the interaction with childhood
      stress in vulnerable individuals. A total of 198 remitted depressed individuals
      performed an n-back task with emotional facial stimuli (happy and sad). Childhood
      events were measured with a questionnaire. Genotype by childhood events
      interactions were analyzed for happy and sad expressions for BDNF (Val66Met;
      rs6265) and COMT (Val158Met; rs4680), individually and combined. BDNF and COMT
      both interacted significantly (P = 0.006 and P = 0.014, respectively) with
      childhood trauma on reaction time for happy faces. For both genes, Met-carriers
      with childhood trauma showed less positive bias for happy faces than those
      without childhood trauma. Val-carriers did not show a differential bias.
      Individuals with childhood trauma and 3 or 4 risk alleles (BDNF and COMT
      combined) showed less positive bias than those without childhood trauma (P =
      0.011). The BDNF * COMT * childhood trauma interaction yielded a P = 0.055, but
      had limited power. A potential weakness is the measurement method of the
      childhood events, as negative bias might have affected participants' recall. Our
      findings endorse the association of BDNF and COMT with stress and depression and
      provide a possible intermediate, i.e. biased processing of positive information.
      Tailoring treatment to specific risk profiles based on genetic susceptibility and
      childhood stress could be promising. 

PMID- 24589357
TI  - Clinical performance of serum isoform [-2]proPSA (p2PSA), and its derivatives
      %p2PSA and the Prostate Health Index, in men aged <60 years: results from a
      multicentric European study.
AB  - OBJECTIVES: To test the hypothesis that [-2]proPSA (p2PSA) and its derivatives
      are more accurate than total prostate-specific antigen (tPSA), free prostate
      specific antigen (fPSA) and fPSA as percentage of tPSA (%fPSA) in detecting
      prostate cancer (PCa) in men aged <60 years. PATIENTS AND METHODS: The analysis
      consisted of a nested case-control study from the PRO- PSA Multicentric European
      Study (PROMEtheuS) project. The primary outcomes were measures of sensibility,
      specificity and accuracy of serum p2PSA, p2PSA as percentage of fPSA (%p2PSA) and
      Beckman Coulter prostate health index (PHI) in men aged <60 years who had
      undergone a prostate biopsy. The potential reduction in the number of unnecessary
      biopsies and the characteristics of the potentially missed PCa cases were
      reported as secondary outcomes. Multivariate logistic regression models were
      complemented by predictive accuracy and decision-curve analyses. RESULTS: Of the
      1036 patients enrolled in the PROMEtheus project, 238 (22.9%) were aged < 60
      years. PCa was found in 67 subjects (28.1%); p2PSA, %p2PSA and PHI values were
      significantly higher (P < 0.001) among these subjects, while no differences were
      found in tPSA, fPSA and %fPSA values. On univariate analysis, %p2PSA (area under
      the curve [AUC]: 0.704) and PHI (AUC: 0.7) were the most accurate predictors, and
      these significantly outperformed tPSA (AUC: 0.549), fPSA (AUC: 0.511) and %fPSA
      (AUC: 0.557) in the prediction of PCa at biopsy (P <= 0.001). In multivariate
      logistic regression models, %p2PSA and PHI achieved independent predictor status
      and significantly increased the accuracy of multivariate models by 6.3 and 7.6%,
      respectively (P <= 0.05). CONCLUSION: PHI and %p2PSA are more accurate than the
      reference standard tests in predicting PCa in young men.

PMID- 24589359
TI  - The effect of simvastatin on chemotactic capability of SDF-1alpha and the
      promotion of bone regeneration.
AB  - The purpose of this study was to investigate the cooperative effects of
      simvastatin (SIM) and stromal cell-derived factor-1alpha (SDF-1alpha) on the
      osteogenic and migration capabilities of mesenchymal stem cells (MSCs), and
      construct a cell-free bone tissue engineering system comprising SIM, SDF-1alpha
      and scaffold. We found that 0.2 MUm SIM significantly increased alkaline
      phosphatase activity (P < 0.05) of mouse bone marrow MSCs with no inhibition of
      cell proliferation, and enhanced the chemotactic capability of SDF-1alpha (P <
      0.05). Next, we constructed a novel cell-free bone tissue engineering system
      using PLGA loaded with SIM and SDF-1alpha, and applied it in critical-sized
      calvarial defects in mice. New bone formation in the defect was evaluated by
      micro-CT, HE staining and immunohistochemistry. The results showed that PLGA
      loaded with SIM and SDF-1alpha promoted bone regeneration significantly more than
      controls. We investigated possible mechanisms, and showed that SDF-1alpha
      combined with SIM increased MSC migration and homing in vivo, promoted
      angiogenesis and enhanced the expression of BMP-2 in newly-formed bone tissue. In
      conclusion, SIM enhanced the chemotactic capability of SDF-1alpha and the cell
      free bone tissue engineering system composed of SIM, SDF-1alpha and scaffold
      promoted bone regeneration in mouse critical-sized calvarial defects. 

PMID- 24589358
TI  - Homing endonucleases from mobile group I introns: discovery to genome
      engineering.
AB  - Homing endonucleases are highly specific DNA cleaving enzymes that are encoded
      within genomes of all forms of microbial life including phage and eukaryotic
      organelles. These proteins drive the mobility and persistence of their own
      reading frames. The genes that encode homing endonucleases are often embedded
      within self-splicing elements such as group I introns, group II introns and
      inteins. This combination of molecular functions is mutually advantageous: the
      endonuclease activity allows surrounding introns and inteins to act as invasive
      DNA elements, while the splicing activity allows the endonuclease gene to invade
      a coding sequence without disrupting its product. Crystallographic analyses of
      representatives from all known homing endonuclease families have illustrated both
      their mechanisms of action and their evolutionary relationships to a wide range
      of host proteins. Several homing endonucleases have been completely redesigned
      and used for a variety of genome engineering applications. Recent efforts to
      augment homing endonucleases with auxiliary DNA recognition elements and/or
      nucleic acid processing factors has further accelerated their use for
      applications that demand exceptionally high specificity and activity. 

PMID- 24589360
TI  - Crosslink density, oxidation and chain scission in retrieved, highly cross-linked
      UHMWPE tibial bearings.
AB  - Irradiated, thermally stabilized, highly cross-linked UHMWPE bearings have
      demonstrated superior wear performance and improved in vitro oxidation resistance
      compared with terminally gamma-sterilized bearings, yet retrieval analysis
      reveals unanticipated in vivo oxidation in these materials despite fewer or no
      measurable free radicals. There has been little evidence to date that the
      oxidation mechanism in thermally stabilized materials is the same as that in
      conventional materials, and so it is unknown whether oxidation in these materials
      is leading to chain scission and a degradation of mechanical properties,
      molecular weight, and crosslink density. The aim of this study was to determine
      whether measured in vivo oxidation in retrieved, highly cross-linked tibial
      bearings corresponds with a decreasing crosslink density. Analysis of three
      tibial bearing materials revealed that crosslink density decreased following in
      vivo duration, and that the change in crosslink density was strongly correlated
      with oxidation. The results suggest that oxidation in highly cross-linked
      materials is causing chain scissions that may, in time, impact the material
      properties. If in vivo oxidation continues over longer durations, there is
      potential for a clinically significant degradation of mechanical properties. 

PMID- 24589362
TI  - Femur shaft fracture at a young age and the risk of subsequent severe injuries
      during childhood: a cohort study.
AB  - BACKGROUND: A child who suffers a fracture or a soft-tissue injury at a young age
      faces an increased risk of subsequent injuries during childhood. This risk could
      be related to personal and family characteristics or to lower-than-average bone
      mineral density. The purpose of this nationwide cohort study was to estimate the
      association between a femur shaft fracture at a young age and the subsequent risk
      of hospitalization for injuries during childhood. METHODS: We compared the
      subsequent risk of hospitalization for injuries during childhood among 1,404
      children (exposed) who were one to three years of age when they suffered a femur
      shaft fracture with the risk among 13,814 randomly selected, gender- and age
      matched femur fracture-free children (unexposed). Hazard ratios (HRs) and 95%
      confidence intervals (CIs) for severe injuries defined as fractures or soft
      tissue injuries requiring hospital admission were estimated in a Cox proportional
      hazards model. RESULTS: Exposed children exhibited no significantly increased
      risk of upper-extremity fractures or soft-tissue injuries during childhood,
      regardless of sex and follow-up time. Boys exhibited a 162% increased risk of
      suffering a lower leg fracture requiring hospital admission (HR?=?2.62, 95% CI:
      1.45-4.71), but the refracture risk was not significant for girls 2.02 (0.58
      6.97). CONCLUSIONS: We found an increased risk for subsequent fractures in the
      lower leg that requires inpatient care during childhood for boys, but not for
      girls, who were one to three years of age when they first suffered a femur shaft
      fracture. This increased fracture risk is probably not simply the result of
      greater risk-taking among boys. The explanation might relate to factors affecting
      the bone quality of the lower leg.

PMID- 24589361
TI  - The role of macrophage phenotype in vascularization of tissue engineering
      scaffolds.
AB  - Angiogenesis is crucial for the success of most tissue engineering strategies.
      The natural inflammatory response is a major regulator of vascularization,
      through the activity of different types of macrophages and the cytokines they
      secrete. Macrophages exist on a spectrum of diverse phenotypes, from "classically
      activated" M1 to "alternatively activated" M2 macrophages. M2 macrophages,
      including the subsets M2a and M2c, are typically considered to promote
      angiogenesis and tissue regeneration, while M1 macrophages are considered to be
      anti-angiogenic, although these classifications are controversial. Here we show
      that in contrast to this traditional paradigm, primary human M1 macrophages
      secrete the highest levels of potent angiogenic stimulators including VEGF; M2a
      macrophages secrete the highest levels of PDGF-BB, a chemoattractant for
      stabilizing pericytes, and also promote anastomosis of sprouting endothelial
      cells in vitro; and M2c macrophages secrete the highest levels of MMP9, an
      important protease involved in vascular remodeling. In a murine subcutaneous
      implantation model, porous collagen scaffolds were surrounded by a fibrous
      capsule, coincident with high expression of M2 macrophage markers, while
      scaffolds coated with the bacterial lipopolysaccharide were degraded by
      inflammatory macrophages, and glutaraldehyde-crosslinked scaffolds were
      infiltrated by substantial numbers of blood vessels, accompanied by high levels
      of M1 and M2 macrophages. These results suggest that coordinated efforts by both
      M1 and M2 macrophages are required for angiogenesis and scaffold vascularization,
      which may explain some of the controversy over which phenotype is the angiogenic
      phenotype. 

PMID- 24589363
TI  - Impact of choice of NRTI in first-line antiretroviral therapy: a cohort analysis
      of stavudine vs. tenofovir.
AB  - OBJECTIVE: In April 2010, South Africa replaced stavudine with tenofovir in first
      line antiretroviral therapy (ART) despite tenofovir's higher cost. We examined
      treatment outcomes over 24 months amongst patients initiated on tenofovir-based
      vs. stavudine-based first-line regimens. METHODS: Prospective cohort analysis of
      3940 patients newly initiating either stavudine-based (April 2009 to March 2010)
      or tenofovir-based (April 2010 to March 2011) ART in Johannesburg, South Africa.
      Cox proportional hazards models and Fine and Gray's competing risk regression
      accounting for death were used to model mortality and loss to follow-up,
      respectively. Linear and log-binomial regression were used to evaluate
      associations with immunologic response and unsuppressed virus (>= 400 copies/ml),
      respectively. RESULTS: About 1878 patients prescribed tenofovir and 2062 patients
      prescribed stavudine were included. One hundred and sixty-six (8.8%) tenofovir
      and 244 (11.8%) stavudine patients died. Three hundred and fifty (18.6%)
      tenofovir and 379 (18.4%) stavudine patients were lost to follow-up over 24
      months on ART. Adjusted regression models showed tenofovir and stavudine were
      comparable regarding death, loss to follow-up, immunologic response and virologic
      status. CONCLUSIONS: We found no difference in mortality, loss to follow-up,
      immunological and virologic outcomes over the first 24-months on ART associated
      with tenofovir compared with stavudine.

PMID- 24589364
TI  - Current status of skeletal anchorage dental applications in orthodontics, part
      II.

PMID- 24589365
TI  - Dying in two acute hospitals: would usual care meet Australian national clinical
      standards?
AB  - The Australian Commission for Quality and Safety in Health Care (ACQSHC) has
      articulated 10 clinical standards with the aim of improving the consistency of
      quality healthcare delivery. Currently, the majority of Australians die in acute
      hospitals. But despite this, no agreed standard of care exists to define the
      minimum standard of care that people should accept in the final hours to days of
      life. As a result, there is limited capacity to conduct audits that focus on the
      gap between current care and recommended care. There is, however, accumulating
      evidence in the end of life literature to define which aspects of care are likely
      to be considered most important to those people facing imminent death. These
      themes offer standards against which to conduct audits. This is very apt given
      the national recommendation that healthcare should be delivered in the context of
      considering people's wishes while always treating people with dignity and
      respect. 

PMID- 24589367
TI  - Weekly patterns, diet quality and energy balance.
AB  - Human behaviour is made up of many repeated patterns and habitual behaviours. Our
      day to day lives are punctuated by work, education, domestic chores, sleep and
      food. Changes in daily patterns such as not working in paid employment or
      attending school on the weekend contribute significantly to changes in dietary
      patterns of food consumption, patterns of physical activity and ultimately energy
      balance. The aim of this paper is to adopt a life-course perspective and explore
      the changes in dietary quality and physical activity patterns across the week
      from young children to elderly adults with a focus on Western cultures. Research
      literature indicates that the dietary quality is somewhat poorer on the weekends,
      characterised by higher fat intakes, higher alcohol intakes and consequently
      higher energy intakes. This increase in energy intake is not necessarily offset
      by an increase in activity, rather an increase in sedentary behaviours. Some
      research has observed an increase of more than 100 cal per day over the weekend
      in American adults. Over the course of one year, this can result in a significant
      increase in body mass. Some of the interventions in tackling obesity and diet
      related behaviours must focus on the changes in the weekend behaviour of
      consumers in terms of both food and activity. These efforts should also focus on
      increasing consumer awareness of the long term consequences of the short lived
      weekend excess as well as putting in place practical measures and interventions
      that are evidence based and targeted to consumer needs.

PMID- 24589366
TI  - Bacterial degradation of chlorophenols and their derivatives.
AB  - Chlorophenols (CPs) and their derivatives are persistent environmental pollutants
      which are used in the manufacture of dyes, drugs, pesticides and other industrial
      products. CPs, which include monochlorophenols, polychlorophenols,
      chloronitrophenols, chloroaminophenols and chloromethylphenols, are highly toxic
      to living beings due to their carcinogenic, mutagenic and cytotoxic properties.
      Several physico-chemical and biological methods have been used for removal of CPs
      from the environment. Bacterial degradation has been considered a cost-effective
      and eco-friendly method of removing CPs from the environment. Several bacteria
      that use CPs as their sole carbon and energy sources have been isolated and
      characterized. Additionally, the metabolic pathways for degradation of CPs have
      been studied in bacteria and the genes and enzymes involved in the degradation of
      various CPs have been identified and characterized. This review describes the
      biochemical and genetic basis of the degradation of CPs and their derivatives. 

PMID- 24589368
TI  - A cohort study on the incidence and outcome of pulmonary embolism in trauma and
      orthopedic patients.
AB  - BACKGROUND: This study aims to determine the incidence of pulmonary embolism (PE)
      in trauma and orthopedic patients within a regional tertiary referral center and
      its association with the pattern of injury, type of treatment, co-morbidities,
      thromboprophylaxis and mortality. METHODS: All patients admitted to our
      institution between January 2010 and December 2011, for acute trauma or elective
      orthopedic procedures, were eligible to participate in this study. Our cohort was
      formed by identifying all patients with clinical features of PE who underwent
      Computed Tomography-Pulmonary Angiogram (CT-PA) to confirm or exclude the
      clinical suspicion of PE, within six months after the injury or the surgical
      procedure.Case notes and electronic databases were reviewed retrospectively to
      identify each patient's venous thromboembolism (VTE) risk factors, type of
      treatment, thromboprophylaxis and mortality. RESULTS: Out of 18,151 patients
      admitted during the study period only 85 (0.47%) patients developed PE (positive
      CT-PA) (24 underwent elective surgery and 61 sustained acute trauma). Of these,
      only 76% of the patients received thromboprophylaxis. Hypertension, obesity and
      cardiovascular disease were the most commonly identifiable risk factors. In 39%
      of the cases, PE was diagnosed during the in-hospital stay. The median time of PE
      diagnosis, from the date of injury or the surgical intervention was 23 days
      (range 1 to 312). The overall mortality rate was 0.07% (13/18,151), but for those
      who developed PE it was 15.29% (13/85). Concomitant deep venous thrombosis (DVT)
      was identified in 33.3% of patients. The presence of two or more co-morbidities
      was significantly associated with the incidence of mortality (unadjusted odds
      ratio (OR) = 3.52, 95% confidence interval (CI) (1.34, 18.99), P = 0.034).
      Although there was also a similar clinical effect size for polytrauma injury on
      mortality (unadjusted OR = 1.90 (0.38, 9.54), P = 0.218), evidence was not
      statistically significant for this factor. CONCLUSIONS: The incidence of VTE was
      comparable to previously reported rates, whereas the mortality rate was lower.
      Our local protocols that comply with the National Institute for Health and
      Clinical Excellence (NICE) guidelines in the UK appear to be effective in
      preventing VTE and reducing mortality in trauma and orthopedic patients.

PMID- 24589369
TI  - Metabolic power and energetic costs of professional Australian Football match
      play.
AB  - OBJECTIVES: To compare the metabolic power demands between positional groups, and
      examine temporal changes in these parameters during Australian Football match
      play. DESIGN: Longitudinal observational study. METHODS: Global positioning
      system data were collected from 39 Australian Football players from the same club
      during 19 Australian Football League competition games over two seasons. A total
      of 342 complete match samples were obtained for analysis. Players were
      categorised into one of six positional groups: tall backs, mobile backs,
      midfielders, tall forwards, mobile forwards and rucks. Instantaneous raw velocity
      data obtained from the global positioning system units was exported to a
      customised spreadsheet which provided estimations of both speed-based (e.g. total
      and high-speed running distance) and derived metabolic power and energy
      expenditure variables (e.g. average metabolic power, high-power distance, total
      energy expenditure). RESULTS: There were significant differences between
      positional groups for both speed-based and metabolic power indices, with
      midfielders covering more total and high-speed distance, as well as greater
      average and overall energy expenditure compared to other positions (all p<0.001).
      There were reductions in total, high-speed, and high-power distance, as well as
      average metabolic power throughout the match (all p<0.001). CONCLUSIONS:
      Positional differences exist for both metabolic power and traditional running
      based variables. Generally, midfielders, followed by mobile forwards and mobile
      backs had greater activity profiles compared to other position groups. We
      observed that the reductions in most metabolic power variables during the course
      of the match are comparable to traditional running based metrics. This study
      demonstrates that metabolic power data may contribute to our understanding of the
      physical demands of Australian Football.

PMID- 24589370
TI  - Changes in leg spring behaviour, plantar loading and foot mobility magnitude
      induced by an exhaustive treadmill run in adolescent middle-distance runners.
AB  - OBJECTIVES: This study aimed to determine adjustments in spring-mass model
      characteristics, plantar loading and foot mobility induced by an exhaustive run.
      DESIGN: Within-participants repeated measures. METHODS: Eleven highly-trained
      adolescent middle-distance runners ran to exhaustion on a treadmill at a constant
      velocity corresponding to 95% of velocity associated with VO2max (17.8 +/- 1.4
      kmh(-1), time to exhaustion=8.8 +/- 3.4 min). Contact time obtained from plantar
      pressure sensors was used to estimate spring-mass model characteristics, which
      were recorded (during 30 s) 1 min after the start and prior to exhaustion using
      pressure insoles. Foot mobility magnitude (a composite measure of vertical and
      medial-lateral mobility of the midfoot) was measured before and after the run.
      RESULTS: Mean contact area (foot to ground), contact time, peak vertical ground
      reaction force, centre of mass vertical displacement and leg compression
      increased significantly with fatigue, while flight time, leg stiffness and mean
      pressure decreased. Leg stiffness decreased because leg compression increased to
      a larger extent than peak vertical ground reaction forces. Step length, step
      frequency and foot mobility magnitude did not change at exhaustion. CONCLUSIONS:
      The stride pattern of adolescents when running on a treadmill at high constant
      velocity deteriorates near exhaustion, as evidenced by impaired leg-spring
      behaviour (leg stiffness) and altered plantar loading.

PMID- 24589371
TI  - Thermic effect of food, exercise, and total energy expenditure in active females.
AB  - OBJECTIVES: Exercise and the thermic effect of food contribute to total energy
      expenditure and overall maintenance of health. The aim of this study was to
      determine the interaction between TEF and exercise on TEE based on meal protein
      content. DESIGN: A randomized, repeated measures study. METHODS: Ten active
      females, of normal body weight, participated. Preliminary maximal aerobic
      capacity (VO2max) was determined. Three additional testing sessions consisted of
      performing a 30-min bout of exercise at 60% VO2max after consumption of a high
      (45% total kcal) or low (15% total kcal) protein meal, or fasted. RESULTS:
      Repeated measures ANOVA indicated a significant main effect for the feeding
      protocols (alpha=.05). The high protein meal elicited a 30.39% and 98.15% greater
      increase in TEF compared to the low protein meal (p=.006) and fasted state
      (p<.001), respectively. The low protein meal resulted in 94.34% greater TEF
      compared to fasted (p<.001). Combined with exercise, high protein meal TEF was
      significantly greater compared to fasted (p=.010) but was not significantly
      greater than the low protein meal (p=.122). Significant differences were not
      found between the low protein meals with exercise compared to fasted conditions
      (p=.094). CONCLUSIONS: Findings of this study provide insight on increased TEE
      under acute high protein feeding conditions as compared to a low protein meal and
      fasted state. Combined with exercise, potential for further increases in TEE
      exists as a result of TEF.

PMID- 24589372
TI  - Predictors of chronic ankle instability after an index lateral ankle sprain: a
      systematic review.
AB  - OBJECTIVES: To identify the predictors of chronic ankle instability after an
      index lateral ankle sprain. DESIGN: Systematic review. METHODS: The databases of
      MEDLINE, CINAHL, AMED, Scopus, SPORTDiscus, Embase, Web of Science, PubMed,
      PEDro, and Cochrane Register of Clinical Trials were searched from the earliest
      record until May 2013. Prospective studies investigating any potential intrinsic
      predictors of chronic ankle instability after an index ankle sprain were
      included. Eligible studies had a prospective design (follow-up of at least three
      months), participants of any age with an index ankle sprain, and had assessed
      ongoing impairments associated with chronic ankle instability. Eligible studies
      were screened and data extracted by two independent reviewers. RESULTS: Four
      studies were included. Three potential predictors of chronic ankle instability,
      i.e., postural control, perceived instability, and severity of the index sprain,
      were investigated. Decreased postural control measured by number of foot lifts
      during single-leg stance with eyes closed and perceived instability measured by
      Cumberland Ankle Instability Tool were not predictors of chronic ankle
      instability. While the results of one study showed that the severity of the
      initial sprain was a predictor of re-sprain, another study did not. CONCLUSIONS:
      Of the three investigated potential predictors of chronic ankle instability after
      an index ankle sprain, only severity of initial sprain (grade II) predicted re
      sprain. However, concerns about validity of the grading system suggest that these
      findings should be interpreted with caution.

PMID- 24589374
TI  - The meaning of "significance" for different types of research [translated and
      annotated by Eric-Jan Wagenmakers, Denny Borsboom, Josine Verhagen, Rogier
      Kievit, Marjan Bakker, Angelique Cramer, Dora Matzke, Don Mellenbergh, and Han L.
      J. van der Maas]. 1969.
AB  - Adrianus Dingeman de Groot (1914-2006) was one of the most influential Dutch
      psychologists. He became famous for his work "Thought and Choice in Chess", but
      his main contribution was methodological--De Groot co-founded the Department of
      Psychological Methods at the University of Amsterdam (together with R. F. van
      Naerssen), founded one of the leading testing and assessment companies (CITO),
      and wrote the monograph "Methodology" that centers on the empirical-scientific
      cycle: observation-induction-deduction-testing-evaluation. Here we translate one
      of De Groot's early articles, published in 1956 in the Dutch journal Nederlands
      Tijdschrift voor de Psychologie en Haar Grensgebieden. This article is more
      topical now than it was almost 60years ago. De Groot stresses the difference
      between exploratory and confirmatory ("hypothesis testing") research and argues
      that statistical inference is only sensible for the latter: "One 'is allowed' to
      apply statistical tests in exploratory research, just as long as one realizes
      that they do not have evidential impact". De Groot may have also been one of the
      first psychologists to argue explicitly for preregistration of experiments and
      the associated plan of statistical analysis. The appendix provides annotations
      that connect De Groot's arguments to the current-day debate on transparency and
      reproducibility in psychological science.

PMID- 24589373
TI  - Sodic alkaline stress mitigation by interaction of nitric oxide and polyamines
      involves antioxidants and physiological strategies in Solanum lycopersicum.
AB  - Nitric oxide (NO) and polyamines (PAs) are two kinds of important signal in
      mediating plant tolerance to abiotic stress. In this study, we observed that both
      NO and PAs decreased alkaline stress in tomato plants, which may be a result of
      their role in regulating nutrient balance and reactive oxygen species (ROS),
      thereby protecting the photosynthetic system from damage. Further investigation
      indicated that NO and PAs induced accumulation of each other. Furthermore, the
      function of PAs could be removed by a NO scavenger, cPTIO. On the other hand,
      application of MGBG, a PA synthesis inhibitor, did little to abolish the function
      of NO. To further elucidate the mechanism by which NO and PAs alleviate alkaline
      stress, the expression of several genes associated with abiotic stress was
      analyzed by qRT-PCR. NO and PAs significantly upregulated ion transporters such
      as the plasma membrane Na(+)/H(+) antiporter (SlSOS1), vacuolar Na(+)/H(+)
      exchanger (SlNHX1 and SlNHX2), and Na(+) transporter and signal components
      including ROS, MAPK, and Ca(2+) signal pathways, as well as several transcription
      factors. All of these play important roles in plant adaptation to stress
      conditions. 

PMID- 24589375
TI  - Host-specificity and morphometrics of female Haemonchus contortus, H. placei and
      H. similis (Nematoda: Trichostrongylidae) in cattle and sheep from shared
      pastures in Sao Paulo State, Brazil.
AB  - To better evaluate the usefulness of female Haemonchus specimens for specific
      identification, we undertook a detailed analysis of the morphology of a
      collection of worms obtained from cattle and sheep in shared pastures. Based on
      the results, we also more precisely evaluated the host-specificity of Haemonchus
      contortus, H. placei and H. similis occurring sympatrically in a farm located in
      the western region of Sao Paulo State, Brazil. A synlophe analysis was employed
      to identify the three species of Haemonchus. In cattle, the predominant species
      was H. similis (90.9%), followed by H. placei (9.1%). With the exception of one
      H. placei specimen, only H. contortus was found in sheep. The longest body length
      was found for H. placei specimens, followed by H. contortus and then H. similis.
      It was possible to distinguish H. similis females from H. contortus and H. placei
      on the basis of vulval structure. The synlophe analysis proved to be very useful
      for identification of H. contortus, H. placei and H. similis in epidemiological
      studies involving different species of ruminants in the same pastures. The
      finding that H. placei and H. similis were adapted to cattle and that H.
      contortus was adapted to sheep also confirmed the high host-specificity of the
      three nematodes species. 

PMID- 24589376
TI  - Balancing cardiovascular (CV) and cancer death among patients with small renal
      masses: modification by CV risk.
AB  - OBJECTIVE: To assess modification of comparative cancer survival by
      cardiovascular (CV) risk and treatment strategy among older patients with small
      renal masses (SRMs). PATIENTS AND METHODS: Patients with localised T1a renal cell
      carcinoma were identified in the Surveillance, Epidemiology and End Results
      Medicare database (1995-2007). Patients were stratified by CV risk, using major
      atherosclerotic CV comorbidities identified by the Framingham Heart Study, to
      compare overall (OS), cancer-specific (CSS), and CV-specific survival (CVSS) for
      those who deferred therapy (DT) to those undergoing either partial (PN) or
      radical nephrectomy (RN). Cox proportional hazards and Fine and Gray competing
      risks regression adjusted for demographics, comorbidities, and tumour size were
      performed. RESULTS: In all, 754 (10.5%) patients had DT, 1849 (25.8%) patients
      underwent PN, and 4574 (63.7%) patients underwent RN. Patients at high CV risk
      who had DT had the greatest CV-to-cancer mortality rate ratio (2.89), and CV risk
      was generally associated with worse OS and CVSS. Patients in the high CV risk
      strata had no difference in CSS between treatment strategies [DT vs PN: hazard
      ratio (HR) 0.59, 95% confidence interval (CI) 0.25-1.41; DT vs RN: HR 0.81, 95%CI
      0.46-1.43)], while there was a 2-4 fold CSS benefit for surgery in the low CV
      risk strata. CONCLUSIONS: Cancer survival was comparable across treatment
      strategies for older patients with SRMs with high risk CV disease. Greater
      attention to CV comorbidity as it relates to competing risks of death and life
      expectancy may be deserved in selecting patients appropriate for active
      surveillance because patients at low CV risk might benefit from surgery.

PMID- 24589377
TI  - A role for the proteasome in the turnover of Sup35p and in [PSI(+) ] prion
      propagation.
AB  - Yeast prions are superb models for understanding the mechanisms of self
      perpetuating protein aggregates formation. [PSI(+) ] stands among the most
      documented yeast prions and results from self-assembly of the translation
      termination factor Sup35p into protein fibrils. A plethora of cellular factors
      were shown to affect [PSI(+) ] formation and propagation. Clearance of Sup35p
      prion particles is however poorly understood and documented. Here, we
      investigated the role of the proteasome in the degradation of Sup35p and in
      [PSI(+) ] prion propagation. We found that cells lacking the RPN4 gene, which
      have reduced intracellular proteasome pools, accumulated Sup35p and have defects
      in [PSI(+) ] formation and propagation. Sup35p is degraded in vitro by the 26S
      and 20S proteasomes in a ubiquitin-independent manner, generating an array of
      amyloidogenic peptides derived from its prion-domain. We also demonstrate the
      formation of a proteasome-resistant fragment spanning residues 83-685 which is
      devoid of the prion-domain that is essential for [PSI(+) ] propagation. Most
      important was the finding that the 26S and 20S proteasomes degrade Sup35p fibrils
      in vitro and abolish their infectivity. Our results point to an overlooked role
      of the proteasome in clearing toxic protein aggregates, and have important
      implications for a better understanding of the life cycle of infectious protein
      assemblies. 

PMID- 24589378
TI  - Resolution of central nervous system astrocytic and endothelial sources of CCL2
      gene expression during evolving neuroinflammation.
AB  - BACKGROUND: The chemokine CCL2 is a critical mediator of neuroinflammation in
      diseases such as multiple sclerosis (MS) and its animal model, experimental
      autoimmune encephalomyelitis (EAE). CCL2 drives mononuclear cell infiltration
      into the central nervous system (CNS), alters expression and distribution of
      microvascular endothelial tight junction proteins, and disrupts the blood-brain
      and blood-spinal cord barriers. Immunohistochemistry has consistently revealed
      astrocytes to be a source of this chemokine during neuroinflammation, while
      providing less uniform evidence that CNS endothelial cells may also express CCL2.
      Moreover, the relative contributions of these cell types to the CNS pool of CCL2
      during MS/EAE are unclear and the aim of this study was to investigate this
      further. METHODS: CCL2 gene expression was determined by qRT-PCR in different
      populations of CNS cells at different times following EAE induced by immunization
      with MOG35-55 peptide and adjuvants, or after injection with adjuvants alone. CNS
      cells types were isolated by two different protocols: bulk isolation to yield
      crude microvascular and parenchymal fractions (containing astrocytes, other glia,
      and neurons), or laser capture microdissection (LCM) to acquire more precisely
      microvascular endothelial cells, astrocytes or other parenchymal cells. RESULTS:
      Both CNS microvessel and parenchymal populations prepared by crude bulk isolation
      showed up-regulation of CCL2 mRNA following MOG immunization or injection of
      adjuvants alone. More exact dissection by LCM revealed microvascular endothelial
      cells and astrocytes to be the specific sources of CCL2 gene induction following
      MOG immunization, while only astrocytes showed elevated CCL2 mRNA in response to
      just adjuvants. Astrocytes displayed the greatest degree of stimulation of CCL2
      gene expression following EAE induction. CONCLUSIONS: High-precision LCM affirmed
      both microvascular endothelial cells and astrocytes as the major CNS sources of
      CCL2 gene expression during EAE. Given the high accessibility of the CNS
      microvascular endothelium, endothelial-derived CCL2 could prove a viable target
      for therapeutic intervention in neuroinflammatory disease.

PMID- 24589379
TI  - Current understandings and perspectives on non-cancer health effects of benzene:
      a global concern.
AB  - OBJECTIVE: Benzene, as a volatile organic compound, is known as one of the main
      air pollutants in the environment. The aim of this review is to summarize all
      available evidences on non-cancerous health effects of benzene providing an
      overview of possible association of exposure to benzene with human chronic
      diseases, specially, in those regions of the world where benzene concentration is
      being poorly monitored. METHODOLOGY: A bibliographic search of scientific
      databases including PubMed, Google Scholar, and Scirus was conducted with key
      words of "benzene toxic health effects", "environmental volatile organic
      compounds", "diabetes mellitus and environmental pollutants", "breast cancer and
      environmental pollution", "prevalence of lung cancer", and "diabetes prevalence".
      More than 300 peer reviewed papers were examined. Experimental and epidemiologic
      studies reporting health effects of benzene and volatile organic compounds were
      included in the study. RESULTS: Epidemiologic and experimental studies suggest
      that benzene exposure can lead to numerous non-cancerous health effects
      associated with functional aberration of vital systems in the body like
      reproductive, immune, nervous, endocrine, cardiovascular, and respiratory.
      CONCLUSION: Chronic diseases have become a health burden of global dimension with
      special emphasis in regions with poor monitoring over contents of benzene in
      petrochemicals. Benzene is a well known carcinogen of blood and its components,
      but the concern of benzene exposure is more than carcinogenicity of blood
      components and should be evaluated in both epidemiologic and experimental
      studies. Aspect of interactions and mechanism of toxicity in relation to human
      general health problems especially endocrine disturbances with particular
      reference to diabetes, breast and lung cancers should be followed up.

PMID- 24589380
TI  - Predictors and impact of time to clinical stability in community-acquired
      pneumococcal pneumonia.
AB  - BACKGROUND: A clinical stability (CS) evaluation is thought to be important in
      community-acquired pneumonia (CAP) treatment, but evidence concerning the time to
      CS (TCS) remains lacking. METHODS: Among consecutive patients hospitalized with
      pneumococcal pneumonia, relationships between TCS and other clinical outcomes
      were examined, and predictors and a predictive TCS score were derived from
      patient characteristics on admission. RESULTS: A total of 144 patients were
      enrolled, including 46% and 27% with moderate and severe pneumonia, respectively,
      defined by the pneumonia severity index (PSI). The median TCS was 2 days, and was
      significantly correlated with the length of hospital stay (r = 0.595); a longer
      TCS was significantly associated with the more presence of poor clinical outcomes
      and ICU stays (adjusted odds ratios: 1.359 and 1.366, respectively). A
      multivariate Cox proportional hazard model revealed an absence of bilateral
      pneumonia (hazard rate (HR): 2.107) or bacteremia (HR: 2.520), and mild or
      moderate pneumonia (HR: 2.798 and 2.515, respectively, versus severe) as
      predictors of CS. A predictive score had moderate discriminating power for the
      prolonged TCS (area under the curve: 0.76), and provided similar predictive
      values for poor clinical outcomes and ICU stays. A score of 3 or more points
      indicated the prolonged TCS, with a sensitivity and specificity of 73.3% and
      70.9%, respectively. CONCLUSIONS: Because TCS has a significant relationship with
      other clinical outcomes of pneumococcal CAP, the prediction of TCS might lead to
      the prevention of complications or an earlier transition to oral therapy. Future
      studies are warranted to validate these results.

PMID- 24589381
TI  - Paratuberculosis: decrease in milk production of German Holstein dairy cows
      shedding Mycobacterium avium ssp. paratuberculosis depends on within-herd
      prevalence.
AB  - Paratuberculosis impairs productivity of infected dairy cows because of reduced
      milk production and fertility and enhanced risk of culling. The magnitude of the
      milk yield depression in individual cows is influenced by factors such as parity,
      the stage of the disease and the choice of test used. The objectives of this case
      control study were to substantiate the influence of the different levels of the
      within-herd prevalence (WHP) on individual milk yield of fecal culture (FC)
      positive cows (FC+) compared with FC-negative herd-mates (FC-), and to estimate
      the magnitude of the deviation of the milk yield, milk components and somatic
      cell count (SCC) in an FC-based study. Of a total of 31 420 cows from 26
      Thuringian dairy herds tested for paratuberculosis by FC, a subset of 1382 FC+
      and 3245 FC- with milk recording data were selected as cases and controls,
      respectively. The FC- cows were matched for the same number and stage of
      lactation (+/-10 days in milk) as one FC+ from the same herd. Within a mixed
      model analysis using the fixed effects of Mycobacterium avium ssp.
      paratuberculosis (MAP) status, lactation number, days in milk, prevalence class
      of farm and the random effect of farm on milk yield per day (kg), the amount of
      fat and protein (mg/dl) and lactose (mg/dl) as well as the SCC (1000/ml) were
      measured. On the basis of least square means, FC+ cows had a lower test-day milk
      yield (27.7+/-0.6 kg) compared with FC- (29.0+/-0.6 kg), as well as a lower milk
      protein content and a slightly diminished lactose concentration. FC status was
      not associated with milk fat percentage or milk SCC. In FC+ cows, reduction in
      milk yield increased with increasing WHP. An interaction of FC status and farm
      was found for the test-day milk yield, and milk protein percentage, respectively.
      We conclude that the reduction in milk yield of FC+ cows compared with FC- herd
      mates is significantly influenced by farm effects and depends on WHP class.
      Owners of MAP-positive dairy herds may benefit from the reduction in WHP not only
      by reducing number of infected individuals but also by diminishing the individual
      losses in milk production per infected cow, and therefore should establish
      control measures. 

PMID- 24589382
TI  - Simulation of photosynthetically active radiation distribution in algal
      photobioreactors using a multidimensional spectral radiation model.
AB  - A numerical method for simulating the spectral light distribution in algal
      photobioreactors is developed by adapting the discrete ordinate method for
      solving the radiative transport equation. The technique, which was developed for
      two and three spatial dimensions, provides a detailed accounting for light
      absorption and scattering by algae in the culture medium. In particular, the
      optical properties of the algal cells and the radiative properties of the turbid
      culture medium were calculated using a method based on Mie theory and that makes
      use of information concerning algal pigmentation, shape, and size distribution.
      The model was validated using a small cylindrical bioreactor, and subsequently
      simulations were carried out for an annular photobioreactor configuration. It is
      shown that even in this relatively simple geometry, nontrivial photon flux
      distributions arise that cannot be predicted by one-dimensional models. 

PMID- 24589383
TI  - Effect of inoculum sources on the anaerobic digestion of rice straw.
AB  - The aim of this study was to evaluate the effect of different inoculum sources on
      the rice straw anaerobic digestion. Six different digestates (DM, SM, CM, MS, AGS
      and PS) were applied as inoculums and their effects were evaluated in batch
      reactors. The results indicated that digested manures were more suitable than
      sludge. Reactors inoculated with digested manures achieved higher, biogas
      production and lignocellulose degradation. The better adaptability of digested
      manures had relationship with its higher cellulase and xylanase activities and
      sufficient nutrients content. DM had the best effect among all three digested
      manures. Reactors inoculated with DM achieved the highest biogas production
      (325.3 mL/g VS) and enzymes activities. The synergism between cellulase and
      xylanase activities played an important role in lignocellulose degradation.

PMID- 24589384
TI  - Victimization and polyvictimization of Spanish children and youth: results from a
      community sample.
AB  - Most research into adolescent victimization and polyvictimization has been
      carried out in the United States and in northern European countries. The present
      study aims to determine the prevalence of victimization and polyvictimization in
      a community sample of Spanish adolescents. The sample consisted of 1,107 youth
      (M=14.52, SD=1.76), 590 males and 517 females, randomly recruited from 7
      secondary schools in a north-eastern region in Spain. The Spanish version of the
      Juvenile Victimization Questionnaire was applied, assessing 6 aggregate
      categories of childhood victimization (conventional crimes, caregiver, peer and
      sibling, witnessed and indirect, sexual, and electronic victimization). A total
      of 83% of adolescents reported at least 1 type of victimization during their
      lives, and 68.6% during the last year. Boys were generally more exposed to
      conventional crimes (68.0%), and girls to emotional abuse by caregivers (23.0%)
      and to sexual (13.9%) and electronic (17.6%) victimization during their lifetime.
      Age differences obtained in victimization rates for the past year confirmed that
      peer and sibling victimization peak in early adolescence (33.9%). Witnessing
      community violence was more frequent in older adolescents (34.7%). Almost 20% of
      the sample was considered as polyvictims (i.e., experienced 4 [corrected] or more
      forms of victimization). Adolescent polyvictims experienced victimization in 4 or
      more domains during their lifetime. This study adds new information on the
      epidemiology of victimization in the international context and is the first to do
      so from the perspective of a country in south-western Europe. It illustrates that
      Spanish youth experience a higher level of victimization than official records
      suggest, and that gender and age should be taken into account when analyzing this
      complex area of study.

PMID- 24589385
TI  - Nature and frequency of services provided by child and family health nurses in
      Australia: results of a national survey.
AB  - OBJECTIVE: Australia has a system of universal child and family health (CFH)
      nursing services providing primary health services from birth to school entry.
      Herein, we report on the findings of the first national survey of CFH nurses,
      including the ages and circumstances of children and families seen by CFH nurses
      and the nature and frequency of the services provided by these nurses across
      Australia. METHODS: A national survey of CFH nurses was conducted. RESULTS: In
      all, 1098 CFH nurses responded to the survey. Over 60% were engaged in delivering
      primary prevention services from a universal platform. Overall, 82.8% reported
      that their service made first contact with families within 2 weeks of birth,
      usually in the home (80.7%). The proportion of respondents providing regular
      support to families decreased as the child aged. Services were primarily health
      centre based, although 25% reported providing services in other locations (parks,
      preschools).The timing and location of first contact, the frequency of ongoing
      services and the composition of families seen by nurses varied across Australian
      jurisdictions. Nurses identified time constraints as the key barrier to the
      delivery of comprehensive services. CONCLUSIONS: CFH nurses play an important
      role in supporting families across Australia. The impact of differences in the
      CFH nursing provision across Australia requires further investigation. What is
      known about the topic? Countries that offer universal well child health services
      demonstrate better child health and developmental outcomes than countries that do
      not. Australian jurisdictions offer free, universal child and family health (CFH)
      nursing services from birth to school entry. What does this paper add? This paper
      provides nation-wide data on the nature of work undertaken by CFH nurses offering
      universal care. Across Australia, there are differences in the timing and
      location of first contact, the frequency of ongoing services and the range of
      families seen by nurses. What are the implications for practitioners? The impact
      for families of the variation in CFH nursing services offered across Australia is
      not known. Further research is required to investigate the outcomes of the
      service provision variations identified in the present study.

PMID- 24589386
TI  - Mesenteric ischemia-reperfusion injury up-regulates certain CC, CXC, and XC
      chemokines and results in multi-organ injury in a time-dependent manner.
AB  - INTRODUCTION: Trauma patients who develop multi-organ dysfunction have increased
      systemic levels of chemotactic cytokines. Ischemia-reperfusion (IR) injury to the
      gut may play a role. The purpose of this study was to examine chemokine
      production in a mouse model of mesenteric IR injury. Given the pre-eminent role
      of the neutrophil, there has been much investigation of the CXC chemokines, but
      very limited research on the CC and XC chemokines. We hypothesized that
      intestinal IR injury would induce remote organ injury and enhance serum CC and XC
      chemokine levels. METHODS: Fasted female C57BL6 mice were anesthetized prior to
      laparotomy. In IR animals, the superior mesenteric artery (SMA) was occluded for
      30, 45, or 75 min, while controls underwent sham laparotomy, n = 5-7 per group.
      After the indicated time point, the incision was closed and the mouse was allowed
      to recover for six hours. Following euthanasia, serum levels of 15 chemokines (10
      CC, 4 CXC, and 1 XC) were assessed and histopathologic analyses performed.
      RESULTS: Seventy-five minutes of SMA occlusion was the key time frame for
      significant serum cytokine level up-regulation, intestinal and remote organ
      injury, and neutrophil influx into tissues. With 75 min of intestinal ischemia,
      significantly elevated serum levels, as compared to shams, were noted for seven
      CC chemokines: MCP-1, MCP-3, MIP-1beta, MIP-3beta, eotaxin, MDC, and RANTES.
      Levels of the XC chemokine lymphotactin also increased. Levels of MIP-2, IP-10,
      and KC/GRO (CXC chemokines) rose significantly. MIP-1alpha levels were only
      significantly increased at 45 min IR. We did not find any significant IR injury
      induced changes in levels of MCP-5, MIP-1gamma, or GCP-2, at any ischemia time
      frame. Serum levels of IL-6 correspondingly increased significantly with longer
      ischemia times. CONCLUSIONS: The novel finding of this study is the demonstration
      of significant systemic increases in the CC chemokines eotaxin, MCP-3, MDC, MIP
      3beta in a time-dependent manner, along with tissue injury. The data suggest a
      complex response to IR injury whereby chemokines that are active on a variety of
      leukocytes may play a role in inducing local and remote tissue injury.

PMID- 24589387
TI  - Estimation and upscaling of dual-permeability model parameters for the transport
      of E. coli D21g in soils with preferential flow.
AB  - Dual-permeability models are increasingly used to quantify the transport of
      solutes and microorganisms in soils with preferential flow. An ability to
      accurately determine the model parameters and their variation with preferential
      pathway characteristics is crucial for predicting the transport of microorganisms
      in the field. The dual-permeability model with optimized parameters was able to
      accurately describe the transport of E. coli D21g in columns with artificial
      macropores of different configurations and lengths at two ionic strength levels
      (1 and 20mM NaCl). Correlations between the model parameters and the structural
      geometry of the preferential flow path were subsequently investigated. Decreasing
      the macropore length produced a decrease in the apparent saturated hydraulic
      conductivity of the macropore domain and an increase in the mass transfer between
      the macropore and matrix domains. The mass transfer coefficient was also found to
      be dependent on the configuration of the preferential flow pathway. A linear
      superposition approach was used to estimate field-scale preferential transport
      behavior for hypothetical fields with different amounts and configurations of
      macropores. Upscaling procedures were numerically investigated to predict this
      field-scale transport behavior from column-scale parameters. The upscaling method
      provided a satisfactory prediction of the field results under the tested
      scenarios. This information will be useful in assessing the risks of microbial
      transport due to preferential flow. 

PMID- 24589389
TI  - Honk if you love Rad Onc! OMG--what about your QMP?

PMID- 24589388
TI  - Diagnostic performance of magnetic resonance imaging and computed tomography for
      advanced retinoblastoma: a systematic review and meta-analysis.
AB  - PURPOSE: To determine and compare the diagnostic performance of magnetic
      resonance imaging (MRI) and computed tomography (CT) for the diagnosis of tumor
      extent in advanced retinoblastoma, using histopathologic analysis as the
      reference standard. DESIGN: Systematic review and meta-analysis. PARTICIPANTS:
      Patients with advanced retinoblastoma who underwent MRI, CT, or both for the
      detection of tumor extent from published diagnostic accuracy studies. METHODS:
      Medline and Embase were searched for literature published through April 2013
      assessing the diagnostic performance of MRI, CT, or both in detecting
      intraorbital and extraorbital tumor extension of retinoblastoma. Diagnostic
      accuracy data were extracted from included studies. Summary estimates were based
      on a random effects model. Intrastudy and interstudy heterogeneity were analyzed.
      MAIN OUTCOME MEASURES: Sensitivity and specificity of MRI and CT in detecting
      tumor extent. RESULTS: Data of the following tumor-extent parameters were
      extracted: anterior eye segment involvement and ciliary body, optic nerve,
      choroidal, and (extra)scleral invasion. Articles on MRI reported results of 591
      eyes from 14 studies, and articles on CT yielded 257 eyes from 4 studies. The
      summary estimates with their 95% confidence intervals (CIs) of the diagnostic
      accuracy of conventional MRI at detecting postlaminar optic nerve, choroidal, and
      scleral invasion showed sensitivities of 59% (95% CI, 37%-78%), 74% (95% CI, 52%
      88%), and 88% (95% CI, 20%-100%), respectively, and specificities of 94% (95% CI,
      84%-98%), 72% (95% CI, 31%-94%), and 99% (95% CI, 86%-100%), respectively.
      Magnetic resonance imaging with a high (versus a low) image quality showed higher
      diagnostic accuracies for detection of prelaminar optic nerve and choroidal
      invasion, but these differences were not statistically significant. Studies
      reporting the diagnostic accuracy of CT did not provide enough data to perform
      any meta-analyses. CONCLUSIONS: Magnetic resonance imaging is an important
      diagnostic tool for the detection of local tumor extent in advanced
      retinoblastoma, although its diagnostic accuracy shows room for improvement,
      especially with regard to sensitivity. With only a few-mostly old-studies, there
      is very little evidence on the diagnostic accuracy of CT, and generally these
      studies show low diagnostic accuracy. Future studies assessing the role of MRI in
      clinical decision making in terms of prognostic value for advanced retinoblastoma
      are needed.

PMID- 24589390
TI  - Plagues.

PMID- 24589391
TI  - Appropriateness, scheduling, and patient preparation.

PMID- 24589392
TI  - The health insurance exchanges and radiology.

PMID- 24589393
TI  - Introduction to the special issue: radiation dose optimization--improving the
      safety of CT.

PMID- 24589394
TI  - Virtual meetings: improving impact and accessibility of CME.

PMID- 24589395
TI  - Dose is not always what it seems: where very misleading values can result from
      volume CT dose index and dose length product.
AB  - PURPOSE: The volume CT dose index (CTDIvol) and the dose-length product, commonly
      reported for examinations performed on clinical CT scanners, should not be used
      as surrogates for patient dose. This is because significant under or
      overestimates of these actual values can occur when there is a mismatch between
      the actual body size of the patient and the 16 cm or 32 cm diameter CTDIvol
      phantoms. This mismatch can be exacerbated in pediatric body examinations because
      of the fact that some manufacturers use the large diameter phantom while other
      manufacturers use the small diameter phantom as the CTDIvol reference phantom.
      METHOD: A clinical example is described for a pediatric patient with a 4-fold
      difference in CTDIvol between a presurgical CT examination and a postsurgical CT
      examination, even though the actual dose absorbed by the patient was about the
      same. Using methods published by the American Association of Physicists in
      Medicine, we calculated the size-specific dose estimate (SSDE), and compared the
      estimated measurement of dose using the SSDE with the CTDIvol. RESULTS: Using
      SSDE significantly reduced the discrepancy in radiation dose estimates of CTDIvol
      in the clinical study, and allowed dose estimate comparisons between scanners to
      be more meaningful. CONCLUSIONS: Radiation dose estimates are more accurate when
      using the SSDE metric in lieu of the CTDIvol metric for reporting and comparing
      patient dose indices.

PMID- 24589396
TI  - Content and style of radiation risk communication for pediatric patients.
AB  - The diagnostic benefits of medical imaging, including CT, must be weighed against
      the risks of ionizing radiation and communicated effectively to patients. Health
      care providers requesting and performing these examinations have a shared
      responsibility for this risk-benefit discussion. Effective and balanced
      communication of these risks requires style as well as content mastery.
      Fundamentals of communication are similar for all patients, but special attention
      is needed in the pediatric setting. 

PMID- 24589397
TI  - Patient perspectives on radiation dose.
AB  - People with genetic cancer syndromes have a special interest in imaging. They
      also have special risk factors with respect to radiation. They need to utilize
      the potential of imaging while keeping in mind concerns about cumulative
      radiation exposure. Before imaging, early detection of problems was limited. With
      imaging, issues can be identified when they are small and a good plan of action
      can be developed early. Operations can be planned and metastatic cancer avoided.
      The positive contribution of imaging to the care of these patients can be
      profound. However, this additional surveillance is not without cost. An average
      patient with 1 of these syndromes will undergo 100 or more scans in their
      lifetime. Imaging professionals should be able to describe the risks and benefits
      of each scan in terms that the patient and the ordering physician can understand
      to make smart decisions about the ordering of scans. Why CT versus MRI? When are
      x-ray or ultrasound appropriate, and when are they not? What are the costs and
      the medical risks for the patient? What value does this picture add for the
      physician? Is there a way to answer the medical question with a test other than a
      scan? Medicine is a team sport, and the patient is an integral member of the
      team. 

PMID- 24589398
TI  - Shared decision-making: is it time to obtain informed consent before radiologic
      examinations utilizing ionizing radiation? Legal and ethical implications.
AB  - Concerns about the possibility of developing cancer due to diagnostic imaging
      examinations utilizing ionizing radiation exposure are increasing. Research
      studies of survivors of atomic bomb explosions, nuclear reactor accidents, and
      other unanticipated exposures to similar radiation have led to varying
      conclusions regarding the stochastic effects of radiation exposure. That high
      doses of ionizing radiation cause cancer in humans is generally accepted, but the
      question of whether diagnostic levels of radiation cause cancer continues to be
      hotly debated. It cannot be denied that overexposure to ionizing radiation beyond
      a certain threshold, which has not been exactly determined, does generate cancer.
      This causes a dilemma: what should patients be informed about the possibility
      that a CT or similar examination might cause cancer later in life? At present,
      there is no consensus in the radiology community as to whether informed consent
      must be obtained from a patient before the patient undergoes a CT or similar
      examination. The author analyzes whether there is a legal duty mandating
      radiologists to obtain such informed consent but also, irrespective of the law,
      whether there an ethical duty that compels radiologists to inform patients of
      potential adverse effects of ionizing radiation. Over the past decade, there has
      been a noticeable shift from a benevolent, paternalistic approach to medical care
      to an autonomy-based, shared-decision-making approach, whereby patient and
      physician work as partners in determining what is medically best for the patient.
      Radiologists should discuss the benefits and hazards of imaging with their
      patients. 

PMID- 24589399
TI  - CTSim: an interactive computer simulation to learn the fundamentals of CT dose
      optimization.

PMID- 24589400
TI  - Improving the application of imaging clinical decision support tools: making the
      complex simple.
AB  - With the promotion and incentivization of electronic health records and
      computerized order entry by CMS, there is a unique opportunity to catalyze the
      use of evidence-based guidelines with the inclusion of clinical decision support
      (CDS) tools. Imaging CDS tools have evolved from static paper algorithms,
      checklists, and scores to interactive systems that provide feedback and
      recommendations with the intent of directing health care providers to deliver
      best practices. Some of the major limitations of first generation imaging CDS
      tools include a lack of comprehensive evidence-based guidelines, limited ability
      to input detailed patient conditions and symptoms, and time-intensive user
      interfaces. Next-generation imaging CDS tools will attempt to close the
      information and interface gaps to provide more meaningful guidance to health care
      providers and improve the delivery of best practices to patients. 

PMID- 24589401
TI  - Techniques and tactics for optimizing CT dose in adults and children: state of
      the art and future advances.
AB  - With growing concern over radiation exposure from CT, dose reduction and
      optimization have become important considerations. Many protocol factors and CT
      technologies influence this dose reduction effort, and as such, users should
      maintain a working knowledge of developments in the field. Individual patient
      factors and scanner-specific details also require care and expertise, which are
      vital to the success of any dose reduction effort. The authors review the content
      of the Virtual Symposium on Radiation Safety in Computed Tomography (University
      of California Dose Optimization and Standardization Endeavor), specifically that
      pertaining to the more practical aspects of dose optimization. These range from
      prescan tips to postscan factors, as well as protocol definition itself. Topics
      discussed include localizer radiograph acquisition, tube current modulation,
      reconstruction methods, and pediatric considerations, with the content biased
      toward a CT technologist or protocol manager. Near-term innovations, including
      new iterative reconstruction methods, tube potential modulation, and dual-energy
      CT, are presented, and their capability for dose reduction is briefly discussed. 

PMID- 24589402
TI  - CT protocol review and optimization.
AB  - To reduce the radiation dose associated with CT scans, much attention is focused
      on CT protocol review and improvement. In fact, annual protocol reviews will soon
      be required for ACR CT accreditation. A major challenge in the protocol review
      process is determining whether a current protocol is optimal and deciding what
      steps to take to improve it. In this paper, the authors describe methods for
      pinpointing deficiencies in CT protocols and provide a systematic approach for
      optimizing them. Emphasis is placed on a team approach, with a team consisting of
      at least one radiologist, one physicist, and one technologist. This core team
      completes a critical review of all aspects of a CT protocol and carefully
      evaluates proposed improvements. Changes to protocols are implemented only with
      consensus of the core team, with consideration of all aspects of the CT
      examination, including image quality, radiation dose, patient care and safety,
      and workflow. 

PMID- 24589403
TI  - Standardization and optimization of CT protocols to achieve low dose.
AB  - The increase in radiation exposure due to CT scans has been of growing concern in
      recent years. CT scanners differ in their capabilities, and various indications
      require unique protocols, but there remains room for standardization and
      optimization. In this paper, the authors summarize approaches to reduce dose, as
      discussed in lectures constituting the first session of the 2013 UCSF Virtual
      Symposium on Radiation Safety and Computed Tomography. The experience of scanning
      at low dose in different body regions, for both diagnostic and interventional CT
      procedures, is addressed. An essential primary step is justifying the medical
      need for each scan. General guiding principles for reducing dose include
      tailoring a scan to a patient, minimizing scan length, use of tube current
      modulation and minimizing tube current, minimizing tube potential, iterative
      reconstruction, and periodic review of CT studies. Organized efforts for
      standardization have been spearheaded by professional societies such as the
      American Association of Physicists in Medicine. Finally, all team members should
      demonstrate an awareness of the importance of minimizing dose.

PMID- 24589404
TI  - Methods for CT automatic exposure control protocol translation between scanner
      platforms.
AB  - PURPOSE: An imaging facility with a diverse fleet of CT scanners faces
      considerable challenges when propagating CT protocols with consistent image
      quality and patient dose across scanner makes and models. Although some protocol
      parameters can comfortably remain constant among scanners (eg, tube voltage,
      gantry rotation time), the automatic exposure control (AEC) parameter, which
      selects the overall mA level during tube current modulation, is difficult to
      match among scanners, especially from different CT manufacturers. METHODS:
      Objective methods for converting tube current modulation protocols among CT
      scanners were developed. Three CT scanners were investigated, a GE LightSpeed 16
      scanner, a GE VCT scanner, and a Siemens Definition AS+ scanner. Translation of
      the AEC parameters such as noise index and quality reference mAs across CT
      scanners was specifically investigated. A variable-diameter poly(methyl
      methacrylate) phantom was imaged on the 3 scanners using a range of AEC
      parameters for each scanner. The phantom consisted of 5 cylindrical sections with
      diameters of 13, 16, 20, 25, and 32 cm. The protocol translation scheme was based
      on matching either the volumetric CT dose index or image noise (in Hounsfield
      units) between two different CT scanners. A series of analytic fit functions,
      corresponding to different patient sizes (phantom diameters), were developed from
      the measured CT data. These functions relate the AEC metric of the reference
      scanner, the GE LightSpeed 16 in this case, to the AEC metric of a secondary
      scanner. RESULTS: When translating protocols between different models of CT
      scanners (from the GE LightSpeed 16 reference scanner to the GE VCT system), the
      translation functions were linear. However, a power-law function was necessary to
      convert the AEC functions of the GE LightSpeed 16 reference scanner to the
      Siemens Definition AS+ secondary scanner, because of differences in the AEC
      functionality designed by these two companies. CONCLUSIONS: Protocol translation
      on the basis of quantitative metrics (volumetric CT dose index or measured image
      noise) is feasible. Protocol translation has a dependency on patient size,
      especially between the GE and Siemens systems. Translation schemes that preserve
      dose levels may not produce identical image quality.

PMID- 24589405
TI  - Practical strategies to reduce pediatric CT radiation dose.
AB  - The objective of this article is to provide a brief review of CT scanning
      radiation sensitivity in children and explain CT scan parameters that affect
      radiation dose. We discuss key factors influencing radiation dose and study
      quality and how these factors can be used to optimize scan protocols with the
      goal of reducing pediatric CT radiation dose without compromising diagnostic
      quality. Finally, we provide some practical tips for reducing radiation doses to
      children. 

PMID- 24589406
TI  - Personalized technologist dose audit feedback for reducing patient radiation
      exposure from CT.
AB  - PURPOSE: The aim of this study was to determine whether providing radiologic
      technologists with audit feedback on doses from CT examinations they conduct and
      education on dose-reduction strategies reduces patients' radiation exposure.
      METHODS: This prospective, controlled pilot study was conducted within an
      integrated health care system from November 2010 to October 2011. Ten
      technologists at 2 facilities received personalized dose audit reports and
      education on dose-reduction strategies; 9 technologists at a control facility
      received no intervention. Radiation exposure was measured by the dose-length
      product (DLP) from CT scans performed before (n = 1,630) and after (n = 1,499)
      the intervention and compared using quantile regression. Technologists were
      surveyed before and after the intervention. RESULTS: For abdominal CT, DLPs
      decreased by 3% to 12% at intervention facilities but not at the control
      facility. For brain CT, DLPs significantly decreased by 7% to 12% at one
      intervention facility; did not change at the second intervention facility, which
      had the lowest preintervention DLPs; and increased at the control facility.
      Technologists were more likely to report always thinking about radiation exposure
      and associated cancer risk and optimizing settings to reduce exposure after the
      intervention. CONCLUSIONS: Personalized audit feedback and education can change
      technologists' attitudes about, and awareness of, radiation and can lower patient
      radiation exposure from CT imaging.

PMID- 24589407
TI  - Radiation dose metrics in CT: assessing dose using the National Quality Forum CT
      patient safety measure.
AB  - PURPOSE: The National Quality Forum (NQF) is a nonprofit consensus organization
      that recently endorsed a measure focused on CT radiation doses. To comply,
      facilities must summarize the doses from consecutive scans within age and
      anatomic area strata and report the data in the medical record. Our purpose was
      to assess the time needed to assemble the data and to demonstrate how review of
      such data permits a facility to understand doses. METHODS AND MATERIALS: To
      assemble the data we used for analysis, we used the dose monitoring software
      eXposure to automatically export dose metrics from consecutive scans in 2010 and
      2012. For a subset of 50 exams, we also collected dose metrics manually, copying
      data directly from the PACS into an excel spreadsheet. RESULTS: Manual data
      collection for 50 scans required 2 hours and 15 minutes. eXposure compiled the
      data in under an hour. All dose metrics demonstrated a 30% to 50% reduction
      between 2010 and 2012. There was also a significant decline and a reduction in
      the variability of the doses over time. CONCLUSION: The NQF measure facilitates
      an institution's capacity to assess the doses they are using for CT as part of
      routine practice. The necessary data can be collected within a reasonable amount
      of time either with automatic software or manually. The collection and review of
      these data will allow facilities to compare their radiation dose distributions
      with national distributions and allow assessment of temporal trends in the doses
      they are using.

PMID- 24589408
TI  - How the human-curated web can save RadiologyInfo.org.

PMID- 24589409
TI  - Radiology residents' attitudes toward recurrent RADPAC political contributions:
      current data and implications for the future.

PMID- 24589410
TI  - Correlates of intentions to use cannabis among US high school seniors in the case
      of cannabis legalization.
AB  - BACKGROUND: Support for cannabis ("marijuana") legalization is increasing in the
      United States (US). Use was recently legalized in two states and in Uruguay, and
      other states and countries are expected to follow suit. This study examined
      intentions to use among US high school seniors if cannabis were to become legally
      available. METHODS: Data from the last five cohorts (2007-2011) of high school
      seniors in Monitoring the Future, an annual nationally representative survey of
      students in the US were utilized. Data were analyzed separately for the 6116
      seniors who reported no lifetime use of cannabis and the 3829 seniors who
      reported lifetime use (weighted Ns). We examined whether demographic
      characteristics, substance use and perceived friend disapproval towards cannabis
      use were associated with (1) intention to try cannabis among non-lifetime users,
      and (2) intention to use cannabis as often or more often among lifetime users, if
      cannabis was legal to use. RESULTS: Ten percent of non-cannabis-using students
      reported intent to initiate use if legal and this would be consistent with a 5.6%
      absolute increase in lifetime prevalence of cannabis use in this age group from
      45.6% (95% CI=44.6, 46.6) to 51.2% (95% CI=50.2, 52.2). Eighteen percent of
      lifetime users reported intent to use cannabis more often if it was legal. Odds
      for intention to use outcomes increased among groups already at high risk for use
      (e.g., males, whites, cigarette smokers) and odds were reduced when friends
      disapproved of use. However, large proportions of subgroups of students normally
      at low risk for use (e.g., non-cigarette-smokers, religious students, those with
      friends who disapprove of use) reported intention to use if legal. Recent use was
      also a risk factor for reporting intention to use as often or more often.
      CONCLUSION: Prevalence of cannabis use is expected to increase if cannabis is
      legal to use and legally available.

PMID- 24589411
TI  - Beyond the drug-terror nexus: drug trafficking and state-crime relations in
      Central Asia.
AB  - BACKGROUND: In the wake of collapse of the Soviet Union, Central Asia has
      transformed into a key hub along the Afghan opiates trafficking routes. Around 30
      percent of the heroin manufactured in Afghanistan is estimated to be smuggled
      through Central Asian republics in its way to booming drug markets in Russia and
      Eastern Europe. METHODS: Building upon available evidence and extensive fieldwork
      research, the article seeks to confute mainstream analyses which emphasize
      connections between criminal and terrorist networks. The focus is on conducive
      factors for the establishment of drug routes in Central Asia, the characteristics
      of drug related networks, and the nature of political-criminal relations across
      the region. RESULTS: It is argued that in all five Central Asia republics
      strategic partnerships have formed between drug traffickers and state actors
      around the exploitation of drug rents and that mafias' influence on politics is
      stronger in Tajikistan and Kyrgyzstan, the region's poorest countries.
      CONCLUSION: By moving the focus from narco-terror to the state-crime connections,
      the article provides a critical insight into political economy issues surrounding
      a complex and multifaceted phenomenon such as the drug trade.

PMID- 24589412
TI  - Neoadjuvant chemotherapy followed by robotic radical hysterectomy in locally
      advanced cervical cancer: a multi-institution study.
AB  - OBJECTIVE: Minimally invasive surgery has been performed in locally advanced
      cervical cancer (LACC) without adverse effect in patient's overall prognosis and
      survival. The aim of this report is to evaluate the feasibility and morbidity of
      total robotic radical hysterectomy (TRRH) with pelvic lymphadenectomy in patients
      with LACC after neo-adjuvant chemotherapy (NACT). METHODS: From February 2008 to
      April 2013 a retrospective data collection of women undergoing TRRH for cervical
      cancer stage FIGO IB2 to IIB, after neo-adjuvant chemotherapy, was conducted at
      "Regina Elena" National Cancer Institute of Rome and European Institute of
      Oncology of Milan. All patients deemed operable underwent TRRH with pelvic
      lymphadenectomy within 4 weeks from the last chemotherapy cycle. RESULTS: Median
      operative time was 225 min (range, 105-387 min). The median blood loss was 150 mL
      (range, 30-700 mL). The median number of removed pelvic lymph nodes was 23
      (range, 8-69). Sixteen patients had an optimal response (12 PCR, 4 pPR1) to
      chemotherapy, 33 patients had a pPR2 and 11 patient showed stable disease.
      Adjuvant therapy was administrated in 36 patients (60%). We experienced one intra
      operative complication and 19 post-operative complications, but no conversions to
      laparotomy were necessary to manage these complications. Six patients received a
      blood transfusion. At the time of this report, with a median follow-up of 28.9
      months, 50 patients (83%) are free from recurrence. CONCLUSION: This experience
      demonstrates the feasibility of TRRH pelvic lymphadenectomy after NACT in LACC
      with good accuracy and safety.

PMID- 24589413
TI  - Hypoxia promotes vasculogenic mimicry formation by inducing epithelial
      mesenchymal transition in ovarian carcinoma.
AB  - OBJECTIVES: The functions of hypoxia and subsequent hypoxia-inducible factor
      1alpha (HIF-1alpha) activation in vasculogenic mimicry (VM) are currently
      unclear. This study aimed to investigate the effects of hypoxia on VM formation
      in ovarian cancer, and explore the possible mechanism involved. METHODS: The
      expression levels of HIF-1alpha, E-cadherin, vimentin, Twist1, Slug, and VE
      cadherin proteins were analyzed by immunohistochemistry in 71 specimens of
      epithelial ovarian cancer. The results were correlated with VM and survival
      analysis. We used a well-established in vitro model of a three-dimensional
      culture to compare VM formation under hypoxia and normoxia in ovarian cancer cell
      lines SKOV3 and OVCAR3. To explore the potential mechanism, we examined the
      effects of hypoxia on the mRNA and protein expression levels of both E-cadherin
      and vimentin. RESULTS: HIF-1alpha expression was correlated with loss of E
      cadherin expression and up-regulated vimentin expression in 11 of the 18 VM
      positive patients. Ovarian cancer with evidence of VM was significantly more
      likely to have high Twist1, Slug, and VE-cadherin expression levels. VM was
      observed in vitro under hypoxia. The ovarian cancer cells presented morphological
      epithelial-mesenchymal transition (EMT)-like changes (more fibroblastoid
      morphology and loss of cellular cohesiveness) under hypoxic conditions. The mRNA
      and protein levels demonstrated the induction of EMT after hypoxia.
      Clinicopathological analysis revealed that both VM and HIF-1alpha expression
      levels presented shorter survival durations. CONCLUSIONS: Hypoxia contributed to
      VM formation by inducing EMT. These results may offer new insights for
      consideration in ovarian cancer treatment strategies.

PMID- 24589414
TI  - The association between cervical cancer screening and mortality from cervical
      cancer: a population based case-control study.
AB  - OBJECTIVE: To estimate the effect of cervical cancer screening on mortality from
      cervical cancer in women between the ages of 20 and 69 residing in Ontario by 5
      year age groups. METHODS: An Ontario population based case-control study of women
      between ages 20 and 69 was performed. Cases were women who were diagnosed with
      cervical cancer between January 1, 1998 and December 31, 2008 who died from
      cervical cancer within this period. Controls were women without a diagnosis of
      cervical cancer between January 1, 1998 and December 31, 2008 who were alive on
      the case's date of death. Exposure was defined as cervical cytology history.
      Conditional logistic regression was used to estimate the strength of association
      between mortality from cervical cancer and screening in 5 year incremental age
      intervals. RESULTS: We identified 1052 cases and 10,494 controls. Less than 2.5%
      of women who died from cervical cancer were under the age of 30. Cervical cancer
      screening performed 3-36 months prior to the date of diagnosis was found to be
      protective of mortality from cervical cancer in women over the age of 30 (odds
      ratio=0.28-0.60; p<0.05 in all strata). In women under the age of 30 cervical
      cancer screening was not found to be protective of mortality from cervical cancer
      (odds ratio=1.58-2.43; non significant). CONCLUSION: No association between
      cervical cancer screening and mortality from cervical cancer under the age of 30
      was found. This could be due to there being a small or having no effect or due to
      the fact that mortality from cervical cancer under the age of 30 is extremely
      rare.

PMID- 24589415
TI  - Linc-RNA-RoR acts as a "sponge" against mediation of the differentiation of
      endometrial cancer stem cells by microRNA-145.
AB  - OBJECTIVES: Recently, large intergenic non-coding ribonucleic acids-RoR (linc
      RoR) was reported to regulate expression of core stem cell transcription factors
      (TFs), but its role in endometrial tumorsphere is still unknown. METHODS:
      Fluorescence in situ hybridization (FISH) was used to characterize linc-RoR
      expression in ETs. After construction of adenovirus vectors carrying green
      fluorescent protein (GFP), these vectors were transfected into ETs to estimate
      the effects of overexpression or knocked down expression of miR-145, linc-RoR or
      Dicer. Flow cytometry was employed to ascertain transfection efficiency, and real
      time polymerase chain reaction (RT-PCR) was employed to compare their levels.
      Colony formation was analyzed using cultured gelatin-coated tissue cultures. miR
      145 potential targeting sites in linc-RoR were mutated using a site-directed
      mutagenesis kit to verify its competing endogenous RNA (ceRNA) effects. RESULTS:
      Expression of linc-RoR and core stem cell TFs was associated with the pluripotent
      state of ETs, whereas miR-145 expression increased after ET differentiation.
      Greater expression of miR-145 could lead to down-regulation of linc-RoR and core
      TFs, and decreased colony formation. Converse effects could be achieved after
      knocked-down miR-145 expression. The effects of miR-145 could be eliminated after
      increasing the expression of linc-RoR in ETs or mutated targeted sequences in
      linc-RoR. Knocked-down Dicer expression could improve the expression of linc-RoR
      and core TFs. CONCLUSIONS: Linc-RoR is a ceRNA and acts as a miR-145 "sponge" to
      inhibit mediation of the differentiation of ETs by miR-145. These results suggest
      that linc-RoR has an important role during endometrial carcinogenesis.

PMID- 24589416
TI  - Adjuvant radiation in early stage, unfavorable histology endometrial carcinoma is
      associated with improved local control and survival.
AB  - OBJECTIVE: Unfavorable histology endometrial carcinomas confer worse prognosis.
      We determined the association of adjuvant radiation on local recurrence and
      survival for unfavorable, early stage endometrial cancer. METHODS: We
      retrospectively identified 125 patients who had a hysterectomy for early stage
      (FIGO IA), unfavorable histology (clear cell, papillary serous or grade 3
      endometrioid), endometrial carcinoma treated between 1992 and 2011. Patients were
      restaged according to current FIGO 2009 guidelines. Primary endpoint was local
      control and secondary endpoints were distant recurrence and overall survival.
      RESULTS: The median age of the cohort was 67 years old with a mean follow up 152
      months. Adjuvant radiation was delivered in 60 patients (48%). There were a total
      of 24 recurrences; 5 had local-regional recurrences, 4 local and distant
      recurrence, 12 distant only recurrences, and 3 had unspecified recurrences. The 5
      year local-regional control was 97.8% in patients who received radiation and
      80.1% in patients who did not receive radiation (p=0.018). The 5-year overall
      survival rate was 68.1% if patients did not receive radiation and 84.9% if they
      did receive radiation (p=0.0062). On univariate analysis, only radiation (HR
      0.12, 95% CI: 0.03 to 0.49, p-value=0.018) was associated with a significant
      increase in local relapse free survival. CONCLUSIONS: Adjuvant radiation therapy
      was significantly associated with an improvement in local-regional control and
      overall survival in patients with unfavorable histology, early stage endometrial
      cancer.

PMID- 24589417
TI  - Cellular immune controls over Epstein-Barr virus infection: new lessons from the
      clinic and the laboratory.
AB  - Epstein-Barr virus (EBV), a human herpesvirus with potent B cell growth
      transforming ability, induces multiple cellular immune responses in the infected
      host. How these host responses work together to prevent virus pathogenicity, and
      how immune imbalance predisposes to disease, remain poorly understood. Here, we
      describe three ongoing lines of enquiry that are shedding new light on these
      issues. These focus on: (i) patients with infectious mononucleosis or its fatal
      equivalent, X-linked lymphoproliferative disease; (ii) EBV infection in a range
      of new, genetically defined, primary immune deficiency states; and (iii)
      experimental infection in two complementary animal models, the rhesus macaque and
      the human haemopoietic stem cell reconstituted mouse. 

PMID- 24589418
TI  - New technique of transanal proctectomy with completely robotic total mesorrectal
      excision for rectal cancer.
AB  - Anterior resection with total mesorectal excision is the standard method of
      rectal cancer resection. However, this procedure remains technically difficult in
      mid and low rectal cancer. A robotic transanal proctectomy with total mesorectal
      excision and laparoscopic assistance is reported in a 57 year old male with BMI
      32 kg/m2 and rectal adenocarcinoma T2N1M0 at 5 cm from the dentate line.
      Operating time was 420 min. Postoperative hospital stay was 6 days and no
      complications were observed. Pathological report showed a 33 cm specimen with
      ypT2N0 adenocarcinoma at 2 cm from the distal margin, complete TME and non
      affected circumferential resection margin. Robotic technology might reduce some
      technical difficulties associated with TEM/TEO or SILS platforms in transanal
      total mesorectal excision. Further clinical trials will be necessary to assess
      this technique.

PMID- 24589420
TI  - Young children 'solve for x' using the Approximate Number System.
AB  - The Approximate Number System (ANS) supports basic arithmetic computation in
      early childhood, but it is unclear whether the ANS also supports the more complex
      computations introduced later in formal education. 'Solving for x' in addend
      unknown problems is notoriously difficult for children, who often struggle with
      these types of problems well into high school. Here we asked whether 4-6-year-old
      children could solve for an unknown addend using the ANS. We presented problems
      either symbolically, using Arabic numerals or verbal number words, or non
      symbolically, using collections of objects while preventing verbal counting.
      Across five experiments, children failed to identify the value of the unknown
      addend when problems were presented symbolically, but succeeded when problems
      were presented non-symbolically. Our results suggest that, well before formal
      exposure to unknown-addend problems, children appear to 'solve for x' in an
      intuitive way, using the ANS. 

PMID- 24589419
TI  - Inflammatory cascades mediate synapse elimination in spinal cord compression.
AB  - BACKGROUND: Cervical compressive myelopathy (CCM) is caused by chronic spinal
      cord compression due to spondylosis, a degenerative disc disease, and
      ossification of the ligaments. Tip-toe walking Yoshimura (twy) mice are reported
      to be an ideal animal model for CCM-related neuronal dysfunction, because they
      develop spontaneous spinal cord compression without any artificial manipulation.
      Previous histological studies showed that neurons are lost due to apoptosis in
      CCM, but the mechanism underlying this neurodegeneration was not fully
      elucidated. The purpose of this study was to investigate the pathophysiology of
      CCM by evaluating the global gene expression of the compressed spinal cord and
      comparing the transcriptome analysis with the physical and histological findings
      in twy mice. METHODS: Twenty-week-old twy mice were divided into two groups
      according to the magnetic resonance imaging (MRI) findings: a severe compression
      (S) group and a mild compression (M) group. The transcriptome was analyzed by
      microarray and RT-PCR. The cellular pathophysiology was examined by
      immunohistological analysis and immuno-electron microscopy. Motor function was
      assessed by Rotarod treadmill latency and stride-length tests. RESULTS: Severe
      cervical calcification caused spinal canal stenosis and low functional capacity
      in twy mice. The microarray analysis revealed 215 genes that showed significantly
      different expression levels between the S and the M groups. Pathway analysis
      revealed that genes expressed at higher levels in the S group were enriched for
      terms related to the regulation of inflammation in the compressed spinal cord. M1
      macrophage-dominant inflammation was present in the S group, and cysteine-rich
      protein 61 (Cyr61), an inducer of M1 macrophages, was markedly upregulated in
      these spinal cords. Furthermore, C1q, which initiates the classical complement
      cascade, was more upregulated in the S group than in the M group. The confocal
      and electron microscopy observations indicated that classically activated
      microglia/macrophages had migrated to the compressed spinal cord and eliminated
      synaptic terminals. CONCLUSIONS: We revealed the detailed pathophysiology of the
      inflammatory response in an animal model of chronic spinal cord compression. Our
      findings suggest that complement-mediated synapse elimination is a central
      mechanism underlying the neurodegeneration in CCM.

PMID- 24589421
TI  - Mixed crop-livestock farming systems: a sustainable way to produce beef?
      Commercial farms results, questions and perspectives.
AB  - Mixed crop-livestock (MC-L) farming has gained broad consensus as an economically
      and environmentally sustainable farming system. Working on a Charolais-area
      suckler cattle farms network, we subdivided the 66 farms of a constant sample,
      for 2 years (2010 and 2011), into four groups: (i) 'specialized conventional
      livestock farms' (100% grassland-based farms (GF), n=7); (ii) 'integrated
      conventional crop-livestock farms' (specialized farms that only market animal
      products but that grow cereal crops on-farm for animal feed, n=31); (iii) 'mixed
      conventional crop-livestock farms' (farms that sell beef and cereal crops to
      market, n=21); and (iv) organic farms (n=7). We analyse the differences in
      structure and in drivers of technical, economic and environmental performances.
      The figures for all the farms over 2 years (2010 and 2011) were pooled into a
      single sample for each group. The farms that sell crops alongside beef miss out
      on potential economies of scale. These farms are bigger than specialized beef
      farms (with or without on-farm feed crops) and all types of farms show comparable
      economic performances. The big MC-L farms make heavier and consequently less
      efficient use of inputs. This use of less efficient inputs also weakens their
      environmental performances. This subpopulation of suckler cattle farms appears
      unable to translate a MC-L strategy into economies of scope. Organic farms most
      efficiently exploit the diversity of herd feed resources, thus positioning
      organic agriculture as a prototype MC-L system meeting the core principles of
      agroecology. 

PMID- 24589422
TI  - Influence of raw material properties upon critical quality attributes of
      continuously produced granules and tablets.
AB  - Continuous manufacturing gains more and more interest within the pharmaceutical
      industry. The International Conference of Harmonisation (ICH) states in its Q8
      'Pharmaceutical Development' guideline that the manufacturer of pharmaceuticals
      should have an enhanced knowledge of the product performance over a range of raw
      material attributes, manufacturing process options and process parameters. This
      fits further into the Process Analytical Technology (PAT) and Quality by Design
      (QbD) framework. The present study evaluates the effect of variation in critical
      raw material properties on the critical quality attributes of granules and
      tablets, produced by a continuous from-powder-to-tablet wet granulation line. The
      granulation process parameters were kept constant to examine the differences in
      the end product quality caused by the variability of the raw materials properties
      only. Theophylline-Lactose-PVP (30-67.5-2.5%) was used as model formulation.
      Seven different grades of theophylline were granulated. Afterward, the obtained
      granules were tableted. Both the characteristics of granules and tablets were
      determined. The results show that differences in raw material properties both
      affect their processability and several critical quality attributes of the
      resulting granules and tablets. 

PMID- 24589423
TI  - Control of groundwater pH during bioremediation: improvement and validation of a
      geochemical model to assess the buffering potential of ground silicate minerals.
AB  - Accurate control of groundwater pH is of critical importance for in situ
      biological treatment of chlorinated solvents. The use of ground silicate minerals
      mixed with groundwater is an appealing buffering strategy as silicate minerals
      may act as long-term sources of alkalinity. In a previous study, we developed a
      geochemical model for evaluation of the pH buffering capacity of such minerals.
      The model included the main microbial processes driving groundwater acidification
      as well as mineral dissolution. In the present study, abiotic mineral dissolution
      experiments were conducted with five silicate minerals (andradite, diopside,
      fayalite, forsterite, nepheline). The goal of the study was to validate the model
      and to test the buffering capacity of the candidate minerals identified
      previously. These five minerals increased the pH from acidic to neutral and
      slightly basic values. The model was revised and improved to represent better the
      experimental observations. In particular, the experiments revealed the importance
      of secondary mineral precipitation on the buffering potential of silicates, a
      process not included in the original formulation. The main secondary phases
      likely to precipitate were identified through model calibration, as well as the
      degree of saturation at which they formed. The predictions of the revised
      geochemical model were in good agreement with the observations, with a
      correlation coefficient higher than 0.9 in most cases. This study confirmed the
      potential of silicates to act as pH control agents and showed the reliability of
      the geochemical model, which can be used as a design tool for field applications.

PMID- 24589424
TI  - Challenges to pharmaceutical policymaking: lessons from Australia's national
      medicines policy.
AB  - OBJECTIVE: National medicines policies (NMP) provide a means for governments to
      achieve their objectives in relation to pharmaceuticals and other medicines. This
      research aimed to identify challenges to implementing the objectives of the
      Australian NMP from the perspective of key stakeholders. METHODS: In 2012 and
      2103, we conducted 30 semistructured interviews with stakeholders involved in the
      discovery, clinical testing, regulation and funding of medicines in Australia. We
      asked participants to describe their careers and to give their opinions on
      specific issues surrounding drug development, clinical research, regulation and
      subsidisation in Australia. Data were analysed using Morse's outline of the
      cognitive basis of qualitative research and Charmaz's outline of data analysis in
      grounded theory. The initial phase of 'open coding' revealed findings that could
      be mapped to three of the four objectives of the NMP. We then conducted 'focussed
      coding' for themes relevant to these objectives. RESULTS: Participants identified
      many issues relevant to the ongoing evolution of the NMP, relating primarily to
      ongoing tensions between the commercial objective of ensuring a viable medicines
      industry, and the non-commercial objectives of ensuring that medicines are safe,
      effective and affordable. There were also several other challenges identified to
      the achievement of both the commercial and non-commercial objectives of the NMP.
      These included limits to government funding, globalisation, consumer advocacy,
      changing scientific paradigms and new information technologies. CONCLUSIONS:
      There are many issues that need to be addressed if policymakers are to achieve
      the best outcomes from the NMP. Tensions between the commercial and non
      commercial objectives of the NMP suggest the need to ensure that one stakeholder
      group's imperatives do not stifle those of other groups. At the same time, there
      are several emerging issues that are likely to concern all stakeholders equally,
      and these are both challenges and opportunities for new kinds of collaboration.
      What is known about the topic? We know that stakeholders have several concerns
      about medicines policy, but little is known about the specific challenges to
      implementing medicines policy from the perspective of those involved. What does
      this paper add? We demonstrate that stakeholders have many concerns that could
      impact the implementation of medicines policies. These relate primarily to
      ongoing tensions between the objective of ensuring a viable medicines industry,
      and the objectives of ensuring that medicines are safe, effective and affordable.
      There are also several issues that potentially pose a challenge to achieving both
      the commercial and non-commercial objectives of the NMP. These include limits to
      government funding, globalisation, consumer advocacy, changing scientific
      paradigms and new information technologies. What are the implications for
      practitioners? Policymakers need to systematically address the barriers to the
      ongoing implementation of the NMP. Policymakers should also ensure that one
      imperative (such as the commercial imperative) does not stifle other objectives.
      Other emerging issues are likely to concern all stakeholders, and these provide
      opportunities for new kinds of collaboration among stakeholders.

PMID- 24589425
TI  - Development of a multivalent paediatric human vaccine for rabies virus in
      combination with Measles-Mumps-Rubella (MMR).

PMID- 24589426
TI  - Movement demands of elite rugby league players during Australian National Rugby
      League and European Super League matches.
AB  - PURPOSE: This study compared the movement demands of players competing in matches
      from the elite Australian and European rugby league competitions. METHODS: Global
      positioning system devices were used to measure 192 performances of forwards,
      adjustables, and outside backs during National Rugby League (NRL; n = 88) and
      European Super League (SL; n = 104) matches. Total and relative distances covered
      overall and at low (0-3.5 m/s), moderate (3.6-5 m/s), and high (>5 m/s) speeds
      were measured alongside changes in movement variables across the early, middle,
      and late phases of the season. RESULTS: The relative distance covered in SL
      matches (95.8 +/- 18.6 m/min) was significantly greater (P < .05) than in NRL
      matches (90.2 +/- 8.3 m/min). Relative low-speed activity (70.3 +/- 4.9 m/min vs
      75.5 +/- 18.9 m/min) and moderate-speed running (12.5 +/- 3.3 m m/min vs 14.2 +/-
      3.8 m/min) were highest (P < .05) in the SL matches, and relative high-speed
      distance was greater (P < .05) during NRL matches (7.8 +/- 2.1 m/min vs 6.1 +/-
      1.7 m/min). CONCLUSIONS: NRL players have better maintenance of high-speed
      running between the first and second halves of matches and perform less low- and
      moderate-speed activity, indicating that the NRL provides a higher standard of
      rugby league competition than the SL.

PMID- 24589427
TI  - An earring incidentally diagnosed and removed through two-step vaginoscopy in a
      pubertal virgin girl with miliary tuberculosis.

PMID- 24589428
TI  - Management of neonatal herpes simplex virus infection and exposure.
AB  - Neonatal herpes simplex virus (HSV) infections are rare but are associated with
      significant morbidity and mortality. Advances in diagnostic modalities to
      identify these infants, as well as the development of safe and effective
      antiviral therapy, have revolutionised the management of affected infants. This
      review will summarise the epidemiology of neonatal HSV infections and discuss the
      management of infants with HSV exposure and infection. 

PMID- 24589429
TI  - Effective treatment of pulmonary tuberculosis restores plasma leptin levels.
AB  - An impaired immune response in tuberculosis patients seems to be related to
      weight loss that coexists with an immunoendocrine imbalance. Thus, wasting is
      well-recognised as a prominent feature of tuberculosis (TB), which may not be
      reversed even after six months of treatment. Adipokines may play a role in the
      immune response to M. tuberculosis, and TB may impair the expression of
      inflammatory adipokines, such as leptin. We aimed to study patients with
      pulmonary TB before and six months after treatment, by measuring plasma leptin,
      soluble leptin receptor and adiponectin, weight and body mass index. Nineteen
      patients with a diagnosis of pulmonary TB were included in the study. Blood
      samples were obtained before and six months after treatment, to measure plasma
      adipokine levels. We found an increase in plasma leptin levels after treatment
      (p<0.05). Even though BMI also increased, the extent was not enough to account
      for the changes in the leptin levels. On the other hand, plasma soluble leptin
      receptor and adiponectin levels did not change significantly after treatment. In
      conclusion, these results suggest that active TB infection may affect the
      expression of leptin, in addition to the wasting that may occur in these
      patients, and that effective TB treatment increases circulating leptin levels,
      probably restoring normal immunological competence.

PMID- 24589430
TI  - Antimicrobial resistance of zoonotic and commensal bacteria in Europe: the
      missing link between consumption and resistance in veterinary medicine.
AB  - The emergence of resistance in food animals has been associated to the
      consumption of antimicrobials in veterinary medicine. Consequently, monitoring
      programs have been designed to monitor the occurrence of antimicrobial resistant
      bacteria. This study analyses the amount of antimicrobial agents used in nine
      European countries from 2005 to 2011, and compares by univariate analysis the
      correlations between consumptions of each of the following antimicrobial classes;
      tetracycline, penicillins, cephalosporins, quinolones and macrolides. An overview
      of resistance in zoonotic and commensal bacteria in Europe focusing on
      Salmonella, Escherichia coli, Campylobacter sp. and Enterococcus sp., during the
      same period of time based on monitoring programs is also assessed. With the
      exception of cephalosporins, linear regressions showed strong positive
      associations between the consumption of the four different antimicrobial classes.
      Substantial differences between countries were observed in the amount of
      antimicrobials used to produce 1 kg of meat. Moreover, large variations in
      proportions of resistant bacteria were reported by the different countries,
      suggesting differences in veterinary practice. Despite the withdrawn of a
      specific antimicrobial from "on farm" use, persistence over the years of bacteria
      resistant to this particular antimicrobial agent, was still observed. There were
      also differences in trends of resistance associated to specific animal species.
      In order to correlate the use of antimicrobial agents to the presence of
      resistance, surveillance of antimicrobial consumption by animal species should be
      established. Subsequently, intervention strategies could be designed to minimize
      the occurrence of resistance.

PMID- 24589431
TI  - EU brings in new tobacco rules to deter young smokers.

PMID- 24589433
TI  - The amyloid hypothesis, time to move on: Amyloid is the downstream result, not
      cause, of Alzheimer's disease.
AB  - The "amyloid hypothesis" has dominated Alzheimer research for more than 20 years,
      and proposes that amyloid is the toxic cause of neural/synaptic damage and
      dementia. If correct, decreasing the formation or removing amyloid should be
      therapeutic. Despite discrepancies in the proposed mechanism, and failed clinical
      trials, amyloid continues to be considered the cause of a degenerative cascade.
      Alternative hypotheses must explain three features: (i) why amyloid toxicity is
      not the etiology of Alzheimer's disease (AD), (ii) what alternative mechanisms
      cause the degeneration and dementia of AD, and (iii) why increased amyloid
      accumulates in the brain in AD. We propose that AD, which occurs in elderly,
      already vulnerable brains, with multiple age-related changes, is precipitated by
      impaired microvascular function, resulting primarily from decreased Notch-related
      angiogenesis. With impaired microvasculature, a lack of vascular endothelial
      derived trophic factors and decreased cerebral blood flow cause the atrophy of
      neural structures. Therapeutic strategies should focus on supporting normal
      angiogenesis.

PMID- 24589435
TI  - Neural correlates of empathic impairment in the behavioral variant of
      frontotemporal dementia.
AB  - OBJECTIVE: Loss of empathy is a symptom of the behavioral variant of
      frontotemporal dementia (bvFTD), constituting a clue for early diagnosis. In this
      study, we directly compared two empathy components (intention attribution [IA]
      and emotion attribution [EA]), correlating them with possible specific patterns
      of gray-matter density reduction within the mentalizing network. METHODS: We
      evaluated IA and EA in 18 mild bvFTD patients compared with 36 healthy controls
      (HCs) using a single nonverbal test. A subgroup entered a voxel-based morphometry
      study. RESULTS: Compared with HC, bvFTD patients showed IA and EA impairments. EA
      performance correlated with gray-matter reduction in the right amygdala, left
      insula, and posterior-superior temporal sulcus extending into the temporoparietal
      junction. CONCLUSION: We proved an empathic impairment, with the ability to infer
      emotional states showing the most severe deficit. These results provide further
      evidence of selective disease-specific vulnerability of the limbic and
      frontoinsular network in bvFTD and highlight the usefulness of empathy assessment
      in early patients.

PMID- 24589434
TI  - Brain tocopherols related to Alzheimer's disease neuropathology in humans.
AB  - Randomized trials of alpha-tocopherol supplements on cognitive decline are
      negative, whereas studies of dietary tocopherols have shown benefit. We
      investigated these inconsistencies by analyzing the relations of alpha- and gamma
      tocopherol brain concentrations to Alzheimer's disease (AD) neuropathology among
      115 deceased participants of the prospective Rush Memory and Aging Project.
      Associations of amyloid load and neurofibrillary tangle severity with brain
      tocopherol concentrations were examined in separate adjusted linear regression
      models. gamma-Tocopherol concentrations were associated with lower amyloid load
      (beta = -2.10, P = .002) and lower neurofibrillary tangle severity (beta = -1.16,
      P = .02). Concentrations of alpha-tocopherol were not associated with AD
      neuropathology, except as modified by gamma-tocopherol: high alpha-tocopherol was
      associated with higher amyloid load when gamma-tocopherol levels were low and
      with lower amyloid levels when gamma-tocopherol levels were high (P for
      interaction = 0.03). Brain concentrations of gamma- and alpha-tocopherols may be
      associated with AD neuropathology in interrelated, complex ways. Randomized
      trials should consider the contribution of gamma-tocopherol.

PMID- 24589436
TI  - Abeta and cognitive change: examining the preclinical and prodromal stages of
      Alzheimer's disease.
AB  - BACKGROUND: High beta-amyloid (Abeta) is associated with faster memory decline in
      healthy individuals and adults with mild cognitive impairment (MCI). However,
      longer prospective studies are required to determine if Abeta-related memory
      decline continues and whether it is associated with increased rate of disease
      progression. METHODS: Healthy controls (HCs; n = 177) and adults with MCI (n =
      48) underwent neuroimaging for Abeta and cognitive assessment at baseline.
      Cognition was reassessed 18 and 36 months later. RESULTS: Compared with low-Abeta
      HCs, high-Abeta HC and MCI groups showed moderate decline in episodic and working
      memory over 36 months. Those with MCI with low Abeta did not show any cognitive
      decline. Rates of disease progression were increased in the high-Abeta HC and MCI
      groups. CONCLUSIONS: In healthy individuals, high Abeta likely indicates that
      Alzheimer's disease (AD)-related neurodegeneration has begun. Once commenced, the
      rate of decline in cognitive function remains constant across the preclinical and
      prodromal stages of AD.

PMID- 24589438
TI  - The N-myc Oncogene: Maximizing its Targets, Regulation, and Therapeutic
      Potential.
AB  - N-myc (MYCN), a member of the Myc family of basic-helix-loop-helix-zipper (bHLHZ)
      transcription factors, is a central regulator of many vital cellular processes.
      As such, N-myc is well recognized for its classic oncogenic activity and
      association with human neuroblastoma. Amplification and overexpression of N-myc
      has been described in other tumor types, particularly those of neural origin and
      neuroendocrine tumors. This review outlines N-myc's contribution to normal
      development and oncogenic progression. In addition, it highlights relevant
      transcriptional targets and mechanisms of regulation. Finally, the clinical
      implications of N-Myc as a biomarker and potential as a target using novel
      therapeutic approaches are discussed.

PMID- 24589437
TI  - Prospective screening for ALK: clinical features and outcome according to ALK
      status.
AB  - The aim of this study was to analyse the clinico-pathological characteristics and
      outcomes of a cohort of French patients who were prospectively screened for
      Anaplastic Lymphoma Kinase (ALK) rearrangement. One hundred and sixteen
      consecutive patients screened for ALK rearrangement to be recruited into a
      crizotinib registration trial were included from eight French centres. ALK
      rearrangement was detected by fluorescence in situ hybridization. Seventeen
      patients (14.6%) were positive for ALK. ALK+ patients were younger (p = 0.049)
      and more likely to be males (p=0.032), non- or light-smokers (p = 0.048) and
      without underlying respiratory disease (p=0.025) compared to ALK- patients.
      Thyroid-transcription factor-1 expression was present in all ALK+ tumours. ALK+
      tumours tended to have lymph node and brain metastases. In multivariate analyses,
      gender, smoking history and N stage were independently associated with ALK
      status. Median overall survival (OS) was not reached for ALK+ patients and was
      significantly longer than for ALK- patients (hazard ratio for death for ALK-
      patients 2.98; 95% CI [1.29-6.90], p=0.01). French ALK+ patients present a
      specific phenotype. ALK rearrangement should be determined to improve OS with an
      effective targeted therapy.

PMID- 24589439
TI  - Ethnic disparities in objectively measured physical activity may be due to
      occupational activity.
AB  - OBJECTIVES: We examined whether Mexican American adults report occupations that
      involve higher levels of objectively assessed physical activity compared with Non
      Hispanic White and Black adults, and if the differences were independent of
      income. METHODS: Data from the 2003-2004 National Health and Nutrition
      Examination Survey (NHANES; N=2707) were analyzed in 2012-2013. An existing
      classification scheme was used to classify self-reported occupation as sedentary,
      low-active, or moderately active. From NHANES accelerometer data, proportion of
      wear time was stratified by intensity. RESULTS: A dose-response relationship was
      found such that workers in more active occupations spent more time in light
      intensity activity and less time engaged in sedentary activities. The findings
      did not suggest a compensation effect for moderate-to-vigorous intensity physical
      activity. Mexican American adults engaged in more activity than Non-Hispanic
      Black or White adults for incomes between $10,000 and $64,999. CONCLUSIONS:
      Mexican American adults may have higher total physical activity levels in NHANES
      because of occupational activity, particularly among lower income households. To
      the extent that light-intensity activity may provide health benefits,
      occupational activity may partly explain the Hispanic paradox.

PMID- 24589440
TI  - Overweight and obesity among low-income women in rural West Virginia and urban
      Los Angeles County.
AB  - We described the prevalence of overweight and obesity among low-income women in
      rural West Virginia (WV) and urban Los Angeles County (LA County). Both
      communities participated in the national Communities Putting Prevention to Work
      program during 2010-2012. In each community, we completed health assessments on
      adult women recruited from public-sector clinics serving low-income populations.
      All participants answered survey questions regarding socio-demographics and
      diets. In both jurisdictions, we assessed obesity using objectively measured
      height and weight (calculated BMI). As part of each community case study, we
      performed multivariable regression analyses to describe the relationships between
      overweight and obesity and selected covariates (e.g., dietary behaviors).
      Overweight and obesity were prevalent among low-income women from WV (73%,
      combined) and LA County (67%, combined). In both communities, race and ethnicity
      appeared to predict the two conditions; however, the associations were not
      robust. In LA County, for example, African American and Hispanic women were 1.4
      times (95% CI=1.12, 1.81) more likely than white women to be overweight and
      obese. Collectively, these subpopulation health data served as an important guide
      for further planning of obesity prevention efforts in both communities. These
      efforts became a part of the subsequent Community Transformation Grants
      portfolio.

PMID- 24589441
TI  - Physical activity from adolescence to young adulthood and bone mineral density in
      young adults from the 1982 Pelotas (Brazil) Birth Cohort.
AB  - OBJECTIVE: To evaluate a prospective association between physical activity (PA)
      and bone mineral density (BMD) in young adults. METHOD: Total body (TB), lumbar
      spine (LS) and femoral neck (FN) BMD were measured in participants from the 1982
      Pelotas Birth Cohort by dual-energy X-ray absorptiometry at 30 y. PA was
      evaluated at 15, 18 (males) and 23 y. RESULTS: 3454 young adults were scanned
      (DXA) at least at one anatomical site. In males, PA at 15 y was associated with
      LS density (beta=0.061 g/cm(2); 95% confidence interval (CI): 0.015; 0.108). A
      positive dose-response effect was found for the association between PA at 18 y
      and BMD. Males in the two highest quartiles of PA at 23 y had significantly
      greater BMD at all anatomical sites than males in the lowest quartile. We
      observed greater BMD at 30 y in boys who were active at least in one of the
      assessments (18 or 23 y) compared to inactive boys at both ages. Females in the
      highest quartile of PA at 23 y showed greater FN density at 30 y (beta=0.020;
      95%CI: 0.001; 0.039). CONCLUSIONS: A physically active pattern is important to
      BMD across the first three decades of life. Potential beneficial effects of PA
      were not entirely lost with advancing age in male young adults.

PMID- 24589442
TI  - The association between demographic and behavioral characteristics and sunburn
      among U.S. adults - National Health Interview Survey, 2010.
AB  - OBJECTIVE: To examine the association between demographic and behavioral
      characteristics and sunburn among U.S. adults. METHOD: We used 2010 National
      Health Interview Survey data (N=24,970) to conduct multivariable logistic
      regressions examining associations with having 1 or more sunburns in the past
      year and having 4 or more sunburns in the past year. RESULTS: Overall, 37.1% of
      adults experienced sunburn in the past year. The adjusted prevalence of sunburn
      was particularly common among adults aged 18-29years (52.0%), those who
      repeatedly burn or freckle after 2weeks in the sun (45.9%), whites (44.3%),
      indoor tanners (44.1%), those with a family history of melanoma (43.9%), and
      those who are US-born (39.5%). Physical activity, alcohol consumption, and
      overweight/obesity were positively associated with sunburn (all P<0.001); sun
      protection behaviors were not significantly associated with sunburn (P=0.35).
      Among those who were sunburned in the past year, 12.1% experienced 4 or more
      sunburns. CONCLUSION: Sunburn is common, particularly among younger adults, those
      with a more sun-sensitive skin type, whites, those with a family history of
      melanoma, the highly physically active, and indoor tanners. Efforts are needed to
      facilitate sun-safety during outdoor recreation, improve the consistency of sun
      protection practices, and prevent sunburn, particularly among these subgroups.

PMID- 24589443
TI  - Usefulness of oblique coronal and sagittal MR images of the knee after double
      bundle and selective anterior cruciate ligament reconstructions.
AB  - BACKGROUND: The use of double-bundle and selective-bundle anterior cruciate
      ligament (ACL) reconstruction is increasing. Few studies have been conducted to
      determine the diagnostic efficacy of additional oblique views of knee magnetic
      resonance imaging (MRI) for grading ACL graft injury for double-bundle and
      selective-bundle ACL reconstructions. PURPOSE: To evaluate the diagnostic value
      of combining oblique coronal and sagittal imaging with orthogonal views for
      diagnosis of ACL graft failure after double-bundle or selective-bundle ACL
      reconstruction. MATERIAL AND METHODS: This retrospective study included 64
      patients who underwent double-bundle or selective-bundle ACL reconstruction
      surgery and received oblique coronal and oblique sagittal MRI of the knee.
      Subjective scoring of the images was performed by two radiologists who assessed
      the possibility of ACL graft failure based on full length view, full width view,
      and margin sharpness according to a 4-point scale. Diagnostic performance for ACL
      graft failure based on orthogonal views alone, ACL views alone, and orthogonal
      views with additional ACL views was evaluated by calculating the sensitivity,
      specificity, and accuracy. RESULTS: The full length scores and total scores on
      ACL views were significantly higher than those of orthogonal views. The
      specificities and accuracies of diagnoses were highest for a combination of
      orthogonal, ACL sagittal, and ACL coronal views. CONCLUSION: After double-bundle
      or selective-bundle ACL reconstruction, oblique sagittal and coronal images of
      the ACL provide better anatomic evaluation of the ACL than orthogonal views and
      specificity and accuracy of diagnoses were improved when oblique views were
      combined.

PMID- 24589444
TI  - Fragment screening reveals salicylic hydroxamic acid as an inhibitor of
      Trypanosoma brucei GPI GlcNAc-PI de-N-acetylase.
AB  - The zinc-metalloenzyme GlcNAc-PI de-N-acetylase is essential for the biosynthesis
      of mature GPI anchors and has been genetically validated in the bloodstream form
      of Trypanosoma brucei, which causes African sleeping sickness. We screened a
      focused library of zinc-binding fragments and identified salicylic hydroxamic
      acid as a GlcNAc-PI de-N-acetylase inhibitor with high ligand efficiency. This is
      the first small molecule inhibitor reported for the trypanosome GPI pathway.
      Investigating the structure activity relationship revealed that hydroxamic acid
      and 2-OH are essential for potency, and that substitution is tolerated at the 4-
      and 5-positions. 

PMID- 24589445
TI  - Comparison of the anti-amyloidogenic effect of O-mannosylation, O
      galactosylation, and O-GalNAc glycosylation.
AB  - Our aim was to explore the effects of functional groups at carbon-2 (C2) of a
      sugar on the conformational properties of the peptide backbone. Three
      monosaccharides, mannose, galactose, and N-acetylgalactosamine (GalNAc), were
      added separately to the serine side-chain of a hamster prion peptide because it
      is a sensitive model for comparing the effect of protein modification on the
      conformational properties of the polypeptide chain. In buffer, this prion peptide
      goes through a gradual coil-to-beta structural conversion and forms amyloid
      fibrils slowly during incubation. Our results showed that a sugar with an N
      acetyl amino group in the equatorial configuration (GalNAc) or with a hydroxyl
      group in the axial configuration (mannose) on C2 had a greater inhibitory effect
      on the amyloidogenesis of the prion peptide than a sugar with the hydroxyl group
      in the equatorial configuration (galactose). We suggest that galactosylation has
      less effect than mannosylation or GalNAc glycosylation on promoting turn
      formation at the glycosylation site and on inhibition of amyloidogenesis. The
      anti-amyloidogenic property of mannose implies that protein mannosylation has an
      anti-aggregation function. 

PMID- 24589446
TI  - Implementation of a new CT colonography service: 5 year experience.
AB  - AIM: To describe our experience using a 5 year audit of computed tomography
      colonography (CTC) practice and identify factors that influence diagnostic
      performance to guide implementation in other centres. MATERIAL AND METHODS:
      Consecutive patients referred for CTC at a single institution over a 5 year
      period were identified, and reporting rates and positive predictive value (PPV)
      calculated for small polyps, large polyps, and colorectal cancer. Diagnostic
      performance was compared using the Chi-squared test, and trends over time were
      examined with logistic regression. The effect of faecal tagging and an
      intravenous spasmolytic were investigated using Fisher's exact test. RESULTS: In
      total, 4355 CTC examinations were performed. Overall reporting rates and PPV were
      17% and 92%, respectively. Negative predictive value (NPV) for cancer was 99.9%.
      A significant decrease in reporting rate (p < 0.001) was accompanied by an
      increase in PPV for small polyps (p = 0.02) following the introduction of faecal
      tagging. Adequacy rates for CTC improved over time (96% to 99%), with improved
      adequacy rates when using a spasmolytic, 98% versus 96% without. A significant
      difference in reporting rates, but not PPV, was found between radiologists.
      CONCLUSION: Accurate colonic investigation using CTC can be delivered safely to a
      high-risk patient population at a single centre. Faecal tagging and an
      intravenous spasmolytic improve diagnostic performance.

PMID- 24589447
TI  - CT-guided radioactive 125I seed implantation treatment of multiple pulmonary
      metastases of hepatocellular carcinoma.
AB  - AIM: To investigate the clinical value of computed tomography (CT)-guided
      radioactive (125)I seed implantation for the treatment of multiple pulmonary
      metastases of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: From March
      2007 to August 2010, 27 HCC patients with pulmonary metastases who had received
      computed tomography (CT)-guided radioactive (125)I seed implantation were
      enrolled in the study. All patients had >= 2 metastatic lesions (mean diameter 2
      +/- 0.6 cm). Under CT-guidance, (125)I seeds were implanted into the pulmonary
      metastases using the plane implantation technique. RESULTS: Among 27 cases,
      complete response, partial response, stable disease, and progressive disease were
      observed in four, 15, six, and two cases, respectively, during 6-48 months (mean
      20.1 +/- 2.2 months) of follow-up CT. The response rate was 92.6%. The mean
      follow-up time after (125)I implantation was 20.1 months (range 6-48 months). The
      survival rates at 1 and 2 years were 67% and 30.8%, respectively, with a median
      survival of 13.5 months. Side effects during the procedure included minor
      pulmonary effusions and pneumothorax. Pulmonary haemorrhage was observed in 18
      cases and haemoptysis occurred in five patients. Radial shadows were observed in
      three cases on follow-up CT images, and seed migration in two cases on follow-up
      spiral CT images. CONCLUSION: CT-guided radioactive (125)I seed implantation may
      be a safe and effective treatment option for HCC patients with multiple pulmonary
      metastases.

PMID- 24589448
TI  - Microwave assistance of labeling hippuric acid by I-131.
AB  - This work presents a novel approach for labeling hippuric acid with I-131 using
      microwaves. It utilizes copper(II) acetate as a catalyst of the labeling. The
      process involves the use of this catalytic copper(II) acetate at low dilutions
      that were nevertheless sufficient to produce labeled hippuric acid with high
      radiochemical purity in a short time. Therefore, the novel technique overcomes
      the limitations of previously reported conventional methods that involve heating.

PMID- 24589449
TI  - Individuals with psychometric schizotypy show similar social but not physical
      anhedonia to patients with schizophrenia.
AB  - Very few studies have examined physical and social anhedonia across the spectrum
      of schizophrenia. In the present study, we recruited three groups of participants
      (n=84 in each group): patients with schizophrenia, schizotypy and non-schizotypy
      as assessed by the Schizotypal Personality Questionnaire (SPQ). All participants
      completed the self-reported trait anhedonia scales (the Revised Physical
      Anhedonia Scale and the Social Anhedonia Scale). The clinical symptoms of
      schizophrenia patients were assessed using the Positive and Negative Syndrome
      Scale (PANSS) and the Scale for Assessment of Negative Symptoms (SANS). We found
      that the three groups differed in both physical and social anhedonia. The
      schizotypy group reported higher levels of physical anhedonia than the non
      schizotypy group, and the patient group reported higher levels of physical
      anhedonia than the schizotypy group. For social anhedonia, the non-schizotypy
      group differed significantly from both the schizotypy and the patient group,
      while no significant difference was found between the last two groups. Our
      findings show that individuals with schizotypy exhibits similar social but not
      physical anhedonia compared with patients with schizophrenia, which further
      suggests that decreased pleasure experiences in the social environment may be a
      valuable target for identification and early intervention in high-risk
      populations. 

PMID- 24589451
TI  - Embryonic oxygen enhances learning ability in hatchling lizards.
AB  - INTRODUCTION: Producing smart offspring is an important fitness trait;
      individuals with enhanced cognitive ability should be more adept at responding to
      complex environmental demands. Cognitive ability can be influenced by conditions
      experienced during embryonic development. Although oxygen is necessary for
      embryonic development, availability can be limited within the nest environment
      because of substrate type, hydric conditions, and temperature. We do not yet
      understand, however, whether oxygen availability during embryonic development
      influences offspring fitness, especially cognitive ability. To address this
      question we incubated Mongolian Racerunner lizard (Eremias argus) eggs under
      hypoxic (12% O2), normoxic (21% O2), and hyperoxic conditions (30% O2). RESULTS:
      Hypoxia not only slowed hatching time, but also resulted in constrained cognitive
      ability relative to hatchlings experiencing normoxic or hyperoxic incubation
      conditions. Oxygen did not influence hatching success, body size or sprint speed
      of hatchlings. CONCLUSIONS: Oxygen availability during embryonic development has
      important influences on incubation duration and cognitive ability of hatchling
      lizards. This study provides the first evidence that oxygen availability during
      embryonic development can modify cognitive ability of oviparous reptiles.

PMID- 24589450
TI  - Parental expressed emotion and suicidal ideation in adolescents with bipolar
      disorder.
AB  - Family environmental variables are risk factors for recurrent courses of mood
      disorder in adolescents. The present study examined the association between
      parental expressed emotion (EE)-critical, hostile and/or emotionally overinvolved
      attitudes toward a concurrently ill offspring-and suicidal ideation in
      adolescents with bipolar disorder. The sample consisted of 95 adolescents with a
      bipolar I or II diagnosis who had experienced a mood episode in the prior 3
      months. Participants (mean age=15.54 years, S.D.=1.4) were interviewed and
      completed questionnaires regarding current and past suicidal ideation prior to
      their participation in a treatment trial. Parents completed five-minute speech
      samples from which levels of EE were assessed. High EE attitudes in parents were
      associated with current suicidal ideation in adolescents. This relationship was
      independent of the effects of age, gender, current depressive or manic symptoms,
      comorbid diagnoses, bipolar I/II subtypes, family adaptability, and family
      cohesion. These results underscore the importance of addressing the emotional
      reactivity of caregivers in treating adolescents with bipolar disorder who have
      suicidal ideation. 

PMID- 24589452
TI  - Twins reunited: scientific and personal perspectives/twin research studies:
      multiple birth effects on IQ and body size; life style, muscles, and metabolism;
      monochorionic dizygotic twin with blood chimerism; amniocentesis for twins/twins
      in the media: identical doctors; freedom fighter for twins; twin scholarships;
      Auguste and Jean-Felix Piccard; twins born apart.
AB  - A reunion of 38-year-old female monozygotic twins took place in Daegu, South
      Korea, on January 14, 2014. Scientific and personal perspectives on this
      extraordinary event are provided. A review of timely twin research follows,
      covering the effects of multiple births on IQ and body size, lifestyle and
      physical fitness associations, a rare case of a dizygotic twin with blood
      chimerism and definitional issues surrounding amniocentesis-related loss in
      multiple birth pregnancies. Interesting and informative mention of twins in the
      media includes twin doctors, a twin freedom fighter, the availability of college
      scholarships for twins, a new book about the Piccard family (two of whose members
      were twins), and co-twins born before and after the new year. A follow-up to a
      previous mention of identical twin biatheletes is also provided. 

PMID- 24589454
TI  - A randomized, controlled, multicenter contraceptive efficacy clinical trial of
      the intravas device, a nonocclusive surgical male sterilization.
AB  - Because of unavoidable complications of vasectomy, this study was undertaken to
      assess the efficacy and safety of male sterilization with a nonobstructive
      intravas device (IVD) implanted into the vas lumen by a mini-surgical method
      compared with no-scalpel vasectomy (NSV). IVDs were categorized into two types:
      IVD-B has a tail used for fixing to the vas deferens (fixed wing) whereas IVD-A
      does not. A multicenter prospective randomized controlled clinical trial was
      conducted in China. The study was comprised of 1459 male volunteers seeking
      vasectomy who were randomly assigned to the IVD-A (n = 487), IVD-B (n = 485) or
      NSV (n = 487) groups and underwent operation. Follow-up included visits at the 3
      rd -6 th and 12 th postoperative months. The assessments of the subjects involved
      regular physical examinations (including general and andrological examinations)
      and semen analysis. The subjects' partners also underwent monitoring for
      pregnancy by monthly interviews regarding menstruation and if necessary, urine
      tests. There were no significant differences in pregnancy rates (0.65% for IVD-A,
      0 for IVD-B and 0.21% for NSV) among the three groups (P > 0.05). The cumulative
      rates of complications at the 12 th postoperative month were zero, 0.9% and 1.7%
      in the three groups, respectively. In conclusion, IVD male sterilization exhibits
      a low risk of long-term adverse events and was found to be effective as a male
      sterilization method, similar to the NSV technique. IVD male sterilization is
      expected to be a novel contraceptive method. 

PMID- 24589453
TI  - Control of organization and function of muscle and tendon by thrombospondin-4.
AB  - Thrombospondins (TSPs) are multifunctional proteins that are deposited in the
      extracellular matrix where they directly affect the function of vascular and
      other cell types. TSP-4, one of the 5 TSP family members, is expressed abundantly
      in tendon and muscle. We have examined the effect of TSP-4 deficiency on tendon
      collagen and skeletal muscle morphology and function. In Thbs4(-/-) mice, tendon
      collagen fibrils are significantly larger than in wild-type mice, and there is no
      compensatory over-expression of TSP-3 and TSP-5, the two TSPs most highly
      homologous to TSP-4, in the deficient mice. TSP-4 is expressed in skeletal
      muscle, and higher levels of TSP-4 protein are associated with the
      microvasculature of red skeletal muscle with high oxidative metabolism. Lack of
      TSP-4 in medial soleus, red skeletal muscle with predominant oxidative
      metabolism, is associated with decreased levels of several specific
      glycosaminoglycan modifications, decreased expression of a TGFbeta receptor beta
      glycan, decreased activity of lipoprotein lipase, which associates with vascular
      cell surfaces by binding to glycosaminoglycans, and decreased uptake of VLDL. The
      soleus muscle is smaller and hind- and fore-limb grip strength is reduced in
      Thbs4(-/-) mice compared to wild-type mice. These observations suggest that TSP-4
      regulates the composition of the ECM at major sites of its deposition, tendon and
      muscle, and the absence of TSP-4 alters the organization, composition and
      physiological functions of these tissues. 

PMID- 24589456
TI  - Mixed extragonadal germ cell tumor arising from the prostate: a rare combination.

PMID- 24589455
TI  - Targeted prostate biopsy: value of multiparametric magnetic resonance imaging in
      detection of localized cancer.
AB  - Prostate cancer is the second most common cancer in men, with 1.1 million new
      cases worldwide reported by the World Health Organization in one recent year.
      Transrectal ultrasound (TRUS)-guided biopsy has been used for the diagnosis of
      prostate cancer for over 2 decades, but the technique is usually blind to cancer
      location. Moreover, the false negative rate of TRUS biopsy has been reported to
      be as high as 47%. Multiparametric magnetic resonance imaging (mp-MRI) includes
      T1- and T2-weighted imaging as well as dynamic contrast-enhanced (DCE) and
      diffusion-weighted imaging (DWI). mp-MRI is a major advance in the imaging of
      prostate cancer, enabling targeted biopsy of suspicious lesions. Evolving
      targeted biopsy techniques-including direct in-bore biopsy, cognitive fusion and
      software-based MRI-ultrasound (MRI-US) fusion-have led to a several-fold
      improvement in cancer detection compared to the earlier method. Importantly, the
      detection of clinically significant cancers has been greatly facilitated by
      targeting, compared to systematic biopsy alone. Targeted biopsy via MRI-US fusion
      may dramatically alter the way prostate cancer is diagnosed and managed.

PMID- 24589457
TI  - Prostate cancer metastasis-driving genes: hurdles and potential approaches in
      their identification.
AB  - Metastatic prostate cancer is currently incurable. Metastasis is thought to
      result from changes in the expression of specific metastasis-driving genes in
      nonmetastatic prostate cancer tissue, leading to a cascade of activated
      downstream genes that set the metastatic process in motion. Such genes could
      potentially serve as effective therapeutic targets for improved management of the
      disease. They could be identified by comparative analysis of gene expression
      profiles of patient-derived metastatic and nonmetastatic prostate cancer tissues
      to pinpoint genes showing altered expression, followed by determining whether
      silencing of such genes can lead to inhibition of metastatic properties. Various
      hurdles encountered in this approach are discussed, including (i) the need for
      clinically relevant, nonmetastatic and metastatic prostate cancer tissues such as
      xenografts of patients' prostate cancers developed via subrenal capsule grafting
      technology and (ii) limitations in the currently available methodology for
      identification of master regulatory genes.

PMID- 24589459
TI  - Androgen-deprivation therapy-induced aggressive prostate cancer with
      neuroendocrine differentiation.
AB  - Most prostate cancers (PCas) are classified as acinar type (conventional)
      adenocarcinoma which are composed of tumor cells with luminal differentiation
      including the expression of androgen receptor (AR) and prostate-specific antigen
      (PSA). There are also scattered neuroendocrine (NE) cells in every case of
      adenocarcinoma. The NE cells are quiesecent, do not express AR or PSA, and their
      function remains unclear. We have demonstrated that IL8-CXCR2-P53 pathway
      provides a growth-inhibitory signal and keeps the NE cells in benign prostate and
      adenocarcinoma quiescent. Interestingly, some patients with a history of
      adenocarcinoma recur with small cell neuroendocrine carcinoma (SCNC) after
      hormonal therapy, and such tumors are composed of pure NE cells that are highly
      proliferative and aggressive, due to P53 mutation and inactivation of the IL8
      CXCR2-P53 pathway. The incidence of SCNC will likely increase due to the
      widespread use of novel drugs that further inhibit AR function or intratumoral
      androgen synthesis. A phase II trial has demonstrated that platinum-based
      chemotherapy may be useful for such therapy-induced tumors.

PMID- 24589458
TI  - Trading in your spindles for blebs: the amoeboid tumor cell phenotype in prostate
      cancer.

PMID- 24589460
TI  - Avanafil for male erectile dysfunction: a systematic review and meta-analysis.
AB  - Avanafil, a potent new selective phosphodiesterase type 5 (PDE5) inhibitor, has
      been developed for the treatment of erectile dysfunction (ED). We carried out a
      systematic review and meta-analysis to assess the efficacy and safety of this
      drug for the treatment of ED. A literature review was performed to identify all
      published randomized, double-blind, placebo-controlled trials of avanafil for the
      treatment of ED. The search included the following databases: MEDLINE, EMBASE and
      the Cochrane Controlled Trials Register. The reference lists of the retrieved
      studies were also investigated. Four publications, involving a total of 1381
      patients, were used in the analysis, including four randomized controlled trials
      (RCTs) that compared avanafil with a placebo. Among the co-primary efficacy end
      points indicating that avanafil 100 mg was more effective than a placebo were
      successful vaginal penetration (SEP2) (the odds ratio (OR) =5.06, 95% confidence
      interval (CI) =3.29-7.78, P< 0.00001) and successful intercourse (SEP3) (OR =
      3.99, 95% CI = 2.80-5.67, P< 0.00001). Men randomized to receive avanafil were
      less likely than those receiving the placebo to drop out due to an adverse event
      (AE) (OR = 1.48, 95% CI = 0.54-4.08, P= 0.44). Specific AEs with avanafil
      included headache and flushing, which were significantly less likely to occur
      with placebo. This meta-analysis indicates that avanafil 100 or 200 mg is an
      effective and well-tolerated treatment for ED. Compared with avanafil 100 mg,
      patients who take avanafil 200 mg are more likely to experience headaches. 

PMID- 24589461
TI  - Perspectives on the clinical management of localized prostate cancer.

PMID- 24589462
TI  - Association between FOXO3A gene polymorphisms and human longevity: a meta
      analysis.
AB  - Numerous studies have shown associations between the FOXO3A gene, encoding the
      forkhead box O3 transcription factor, and human or specifically male longevity.
      However, the associations of specific FOXO3A polymorphisms with longevity remain
      inconclusive. We performed a meta-analysis of existing studies to clarify these
      potential associations. A comprehensive search was conducted to identify studies
      of FOXO3A gene polymorphisms and longevity. Pooled odds ratios (ORs) and 95%
      confidence intervals (CIs) were calculated by comparing the minor and major
      alleles. A total of seven articles reporting associations of FOXO3A polymorphisms
      with longevity were identified and included in this meta-analysis. These
      comprised 11 independent studies with 5241 cases and 5724 controls from different
      ethnic groups. rs2802292, rs2764264, rs13217795, rs1935949 and rs2802288
      polymorphisms were associated with human longevity (OR = 1.36, 95% CI = 1.10
      1.69, P= 0.005; OR = 1.20, 95% CI = 1.04-1.37, P= 0.01; OR = 1.27, 95% CI = 1.10
      1.46, P= 0.001; OR = 1.14, 95% CI = 1.01-1.27 and OR = 1.24, 95% CI = 1.07-1.43,
      P= 0.003, respectively). Analysis stratified by gender indicated significant
      associations between rs2802292, rs2764264 and rs13217795 and male longevity (OR =
      1.54, 95% CI = 1.33-1.79, P < 0.001; OR = 1.38, 95% CI = 1.15-1.66, P= 0.001; and
      OR = 1.39, 95% CI = 1.15-1.67, P= 0.001), but rs2802292, rs2764264 and rs1935949
      were not linked to female longevity. Moreover, our study showed no association
      between rs2153960, rs7762395 or rs13220810 polymorphisms and longevity. In
      conclusion, this meta-analysis indicates a significant association of five FOXO3A
      gene polymorphisms with longevity, with the effects of rs2802292 and rs2764264
      being male-specific. Further investigations are required to confirm these
      findings.

PMID- 24589463
TI  - Bulbocavernosus muscle area measurement: a novel method to assess androgenic
      activity.
AB  - Serum testosterone does not correlate with androgen tissue activity, and it is
      critical to optimize tools to evaluate such activity in males. Ultrasound
      measurement of bulbocavernosus muscle (BCM) was used to assess the relationship
      between the number of CAG repeats (CAGn) in the androgen receptor (AR) and the
      BCM size; the changes in the number of CAGn over age were also evaluated.
      Transperineal ultrasound measurement of the BCM was also performed. AR CAGn were
      determined by high performance liquid chromatography, and morning hormone levels
      were determined using immunoassays. Forty-eight men had CAG repeat analysis.
      Twenty-five were <30 years of age, mean 23.7 years (s.d. = 3.24) and 23 were >45
      years of age, mean 53 years (s.d. = 5.58). The median CAGn was 21 (13-29). BCM
      area was greater when the number of CAGn were <18 as compared to the number of
      CAGn >24 (P = 0.04). There was a linear correlation between the number of CAGn
      and the BCM area R 2 = 16% (P = 0.01). In the 45 to 65-years-old group, a much
      stronger negative correlation (R 2 = 29%, P = 0.01) was noticed. In the 19 to 29
      years-old group, no such correlation was found (R 2 = 4%, P = 0.36). In older
      men, the number of CAGn increased with age (R 2 = 32%, P = 0.01). The number of
      CAGn in the AR correlates with the area of the BCM. Ultrasound assessment of the
      BCM is an effective surrogate to evaluate end-organ activity of androgens. The
      number of CAGn may increase with age.

PMID- 24589464
TI  - Poly (ADP-ribose) polymerase inhibitor: an evolving paradigm in the treatment of
      prostate cancer.
AB  - Recent phase I studies have reported single-agent activities of poly (ADP-ribose)
      polymerase (PARP) inhibitor in sporadic and in BRCA-mutant prostate cancers. Two
      of the most common genetic alterations in prostate cancer, ETS gene rearrangement
      and loss of PTEN, have been linked to increased sensitivity to PARP inhibitor in
      preclinical models. Emerging evidence also suggests that PARP1 plays an important
      role in mediating the transcriptional activities of androgen receptor (AR) and
      ETS gene rearrangement. In this article, the preclinical work and early-phase
      clinical trials in developing PARP inhibitor-based therapy as a new treatment
      paradigm for metastatic prostate cancer are reviewed. 

PMID- 24589465
TI  - Prognostic role of C-reactive protein in prostate cancer: a systematic review and
      meta-analysis.
AB  - Several studies have reported that C-reactive protein (CRP), an inflammation
      biomarker, may be associated with the prognosis of prostate cancer (PCa). The
      objective of this systematic review is to summarize the predictive role of CRP
      for survival in PCa as reported in previous studies. Related studies were
      identified, and evaluated for quality through multiple search strategies. Data
      was collected from studies comparing overall and cancer-specific survival (CSS)
      in patients with elevated CRP levels and those having lower levels. However, for
      progression-free survival (PFS), data were collected according to the log of CRP.
      The hazard ratio (HR) and its 95% confidence interval (CI) were used to assess
      the strength of associations. A total of nine studies (n = 1,497) were evaluated
      in this meta-analysis (five for overall survival (OS), four for CSS and two for
      PFS). For OS and PFS, the pooled HR of CRP was statistically significant at 1.51
      (95% CI, 1.28-1.79) and 1.50 (95% CI, 1.25-1.81), respectively. For CSS, the
      pooled HR was 1.91 (95% CI, 1.36-2.69) with higher CRP expression in PCa, which
      strongly indicates poorer survival in PCa. This study demonstrates that CRP may
      have a critical prognostic value in patients with prostatic cancer. 

PMID- 24589466
TI  - Relationships among androgen receptor CAG repeat polymorphism, sex hormones and
      penile length in Han adult men from China: a cross-sectional study.
AB  - This study aimed to investigate the correlations among androgen receptor (AR) CAG
      repeat polymorphism, sex hormones and penile length in healthy Chinese young
      adult men. Two hundred and fifty-three healthy men (aged 22.8 +/- 3.1 years) were
      enrolled. The individuals were grouped as CAG short (CAG S ) if they harbored
      repeat length of <= 20 or as CAG long (CAG L ) if their CAG repeat length was
      >20. Body height/weight, penile length and other parameters were examined and
      recorded by the specified physicians; CAG repeat polymorphism was determined by
      the polymerase chain reaction (PCR) method; and the serum levels of the sex
      hormones were detected by radioimmunoassay. Student's t-test or linear regression
      analysis was used to assess the associations among AR CAG repeat polymorphism,
      sex hormones and penile length. This investigation showed that the serum total
      testosterone (T) level was positively associated with the AR CAG repeat length (P
      = 0.01); whereas, no significant correlation of T or AR CAG repeat polymorphism
      with the penile length was found (P = 0.593). Interestingly, an inverse
      association was observed between serum prolactin (PRL) levels and penile length
      by linear regression analyses (beta= -0.024, P = 0.039, 95% confidence interval
      (CI): -0.047, 0). Collectively, this study provides the first evidence that serum
      PRL, but not T or AR CAG repeat polymorphism, is correlated with penile length in
      the Han adult population from northwestern China.

PMID- 24589468
TI  - Diffuse scattering in metallic tin polymorphs.
AB  - The lattice dynamics of the metallic tin beta and gamma polymorphs has been
      studied by a combination of diffuse scattering, inelastic x-ray scattering and
      density functional perturbation theory. The non-symmorphic space group of the
      beta-tin structure results in unusual asymmetry of thermal diffuse scattering.
      Strong resemblance of the diffuse scattering intensity distribution in beta and
      gamma-tin were observed, reflecting the structural relationship between the two
      phases and revealing the qualitative similarity of the underlying electronic
      potential. The strong influence of the electron subsystem on inter-ionic
      interactions creates anomalies in the phonon dispersion relations. All observed
      features are described in great detail by the density functional perturbation
      theory for both beta- and gamma-tin at arbitrary momentum transfers. The combined
      approach delivers thus a complete picture of the lattice dynamics in harmonic
      description.

PMID- 24589467
TI  - Next generation patient-derived prostate cancer xenograft models.

PMID- 24589469
TI  - Combining internal- and external-training-load measures in professional rugby
      league.
AB  - PURPOSE: This study investigated the effect of training mode on the relationships
      between measures of training load in professional rugby league players. METHODS:
      Five measures of training load (internal: individualized training impulse,
      session rating of perceived exertion; external-body load, high-speed distance,
      total impacts) were collected from 17 professional male rugby league players over
      the course of two 12-wk preseason periods. Training was categorized by mode
      (small-sided games, conditioning, skills, speed, strongman, and wrestle) and
      subsequently subjected to a principal-component analysis. Extraction criteria
      were set at an eigenvalue of greater than 1. Modes that extracted more than 1
      principal component were subjected to a varimax rotation. RESULTS: Small-sided
      games and conditioning extracted 1 principal component, explaining 68% and 52% of
      the variance, respectively. Skills, wrestle, strongman, and speed extracted 2
      principal components each explaining 68%, 71%, 72%, and 67% of the variance,
      respectively. CONCLUSIONS: In certain training modes the inclusion of both
      internal and external training-load measures explained a greater proportion of
      the variance than any 1 individual measure. This would suggest that in training
      modes where 2 principal components were identified, the use of only a single
      internal or external training-load measure could potentially lead to an
      underestimation of the training dose. Consequently, a combination of internal-
      and external-load measures is required during certain training modes.

PMID- 24589470
TI  - Ex-vivo study of hybrid energy technology using a human skin model.
AB  - BACKGROUND: More aging adults and the social acceptance of aesthetic treatments
      have increased the demand for minimally invasive aesthetic treatments. Skin
      resurfacing is very effective at improving aging symptoms, including wrinkles and
      skin imperfections. Following the negative effects of full skin resurfacing, in
      addition to a very long downtime, fractional lasers and fractional radiofrequency
      (RF) technologies were introduced, since gaining popularity. Their efficacy,
      along with minimal downtime, has enabled an effective and safer treatment. A
      novel technology based on fractional Hybrid EnergyTM (HE), combines RF and an
      additional electrical energy for enhancing the thermal effect. OBJECTIVE: This
      study evaluated the morphological and histological effects of the new HE
      technology on epidermal and dermal skin layers, using an ex-vivo human skin
      model. METHODS: Human skin samples were collected and treated ex-vivo with the HE
      applicator. The effect was evaluated by skin histology and quantitative analysis
      by assays of collagen fibers, elastin and glycosaminoglycan (GAGs) dosages,
      reflecting the hyaluronic acid content, in addition to epidermal mitotic index
      evaluation. RESULTS: Histology demonstrated immediate and long-term HE effects on
      both epidermal and dermal skin layers with a direct correlation between the
      treatment parameters and effects. Results demonstrated a significant increase of
      the epidermal mitotic index, significant dermal collagen remodeling and
      significant increases in both epidermal and dermal GAGs. CONCLUSIONS: HE
      technology significantly affected collagen remodeling and an increase in mid to
      deep dermis GAGs in addition to epidermal mitotic index, resulting in long term
      structural and biochemical dermal and epidermal improvement.

PMID- 24589471
TI  - Radical prostatectomy or radiotherapy in high-risk prostate cancer: a systematic
      review and metaanalysis.
AB  - BACKGROUND: Radical prostatectomy (RP) is one of the treatment options for
      localized, high-risk prostate cancer (PC), but it has never been compared with
      external beam radiotherapy (RT), which is an alternative approach, in a large
      randomized trial. To compare the outcomes of patients treated with surgery versus
      RT, we performed a metaanalysis of available studies on this topic. MATERIALS AND
      METHODS: We performed a search of MEDLINE, EMBASE, Web of Science, SCOPUS, and
      The Cochrane Central Register of Controlled Trials (CENTRAL) for randomized or
      observational studies that investigated overall survival (OS) and PC-specific
      mortality (PCSM) risks in relation to use of surgery or RT in patients with high
      risk PC. Fixed- and random-effect models were fitted to estimate the summary odds
      ratio (OR). Between-study heterogeneity was tested using chi(2) statistics and
      measured using the I(2) statistic. Publication bias was evaluated using a funnel
      plot and Egger regression asymmetry test. RESULTS: Seventeen studies were
      included (1 randomized and 16 retrospective). RP was associated with improved OS
      (OR, 0.51; 95% confidence interval [CI], 0.38-0.68; P < .00001), PCSM (OR, 0.56;
      95% CI, 0.37-0.85; P = .007), and non-PCSM (OR, 0.53; 95% CI, 0.35-0.8; P = .002)
      compared with RT. Biochemical relapse-free survival rates were similar to those
      of RT. CONCLUSION: Overall and cancer-specific mortality rates appear to be
      better with RP compared with RT in localized, high-risk PC. Surgery is also
      associated with a 50% decreased risk of non-PCSM compared with RT.

PMID- 24589472
TI  - Thymine dimer splitting in the T<>T-G trinucleotide model system: a semiclassical
      dynamics and TD-DFT study.
AB  - The mechanism leading to bond cleavage of a thymine-thymine cyclobutane dimer
      (T<>T) in a model system consisting of the dimer flanked by guanine trinucleotide
      was studied using semiclassical dynamics simulation. Pulsed laser excitation of
      the guanine molecule is found to cause electron transfer from the guanine
      molecule to the dimer, which then dissociates via sequential cleavage of the
      C5C5' and C6C6' bonds. Subsequently, electrons transfer back to the guanine
      molecule as the dimer splits into two monomers. The splitting of the cyclobutane
      dimer was found to be in the femtosecond time scale.

PMID- 24589473
TI  - Removal of heavy metal using poly (N-vinyl imidazole)-grafted-carboxymethylated
      starch.
AB  - Carboxymethyl starch (CMS) grafted with N-vinyl imidazole was investigated for
      heavy metal removal from aqueous solutions. Poly (N-vinyl imidazole)-grafted
      carboxymethyl starch (PVI-g-CMS) was prepared in aqueous solution using potassium
      persulfate (KPS) as initiator. The produced grafted copolymer was characterized
      by FTIR, TGA, surface area and elemental analysis. The grafted material was used
      for the sorption of Mn(II), Zn(II) and Cd(II). Uptake parameters such as affinity
      of metal ions, effect of metal ion concentration, adsorbent amount and agitation
      time were investigated. The polymers were more sensitive to Cd(II) and Zn(II) and
      the order of metal ion binding was Cd(II)>Zn(II)>Mn(II). The adsorption data was
      fitted very well in a Freundlich isotherm equation and the kinetics of adsorption
      was found to follow the pseudo-first order kinetic model. 

PMID- 24589474
TI  - [Asymptomatic hyperpigmented lesions in neck and periareolar area].

PMID- 24589475
TI  - Boron deficiency results in early repression of a cytokinin receptor gene and
      abnormal cell differentiation in the apical root meristem of Arabidopsis
      thaliana.
AB  - The development of Arabidopsis thaliana was dramatically altered within few hours
      following boron (B) deprivation. This effect was particularly evident in the
      apical root meristem. The essentiality of boron in plants has been clearly linked
      to its structural role in the cell wall, however the diversity and rapidity
      alterations of plant organogenesis when the micronutrient is absent suggest that
      B deficiency could also affect gene regulation during plant development.
      Therefore, the effect of B deficiency on cell elongation, apical root meristem
      cell division, and early differentiation of root tissues was investigated in A.
      thaliana seedlings. Dark-growth experiments indicated that hypocotyl elongation
      was inhibited 2 days after removing B, but apical root growth ceased almost
      immediately following B deprivation. Detection of cycline B1 by GUS staining of a
      promoter-reporter construct revealed that low B led to a reduced zone of cell
      division. The expression of CRE1/WOL/AHK4, encoding an integral membrane protein
      with histidine kinase domain that mediates cytokinin signaling and root xylem
      differentiation, was inhibited under B deficiency resulting in arrested xylem
      development at the protoxylem stage. Because the transition from cell division to
      cell differentiation in apical root meristems is controlled by cytokinins, this
      result support the hypothesis that signaling mechanisms during cell
      differentiation and organogenesis are highly sensitive to B deficiency, and
      together with previous reports that link the micronutrient with auxin or ethylene
      control of root architecture, suggests that B could play a role in regulation of
      hormone mediated early plant development signaling. 

PMID- 24589476
TI  - Induction of extracellular defense-related proteins in suspension cultured-cells
      of Daucus carota elicited with cyclodextrins and methyl jasmonate.
AB  - Suspension cultured-cells (SCC) of Daucus carota were used to evaluate the effect
      of methyl jasmonate and cyclodextrins, separately or in combination, on the
      induction of defense responses, particularly the accumulation of pathogenesis
      related proteins. A comparative study of the extracellular proteome (secretome)
      between control and elicited carrot SCC pointed to the presence of amino acid
      sequences homologous to glycoproteins which have inhibitory activity against the
      cell-wall-degrading enzymes secreted by pathogens and/or are induced when carrot
      cells are exposed to a pathogen elicitor. Other amino acid sequences were
      homologous to Leucine-Rich Repeat domain-containing proteins, which play an
      essential role in defense against pathogens, as well as in the recognition of
      microorganisms, making them important players in the innate immunity of this
      plant. Also, some tryptic peptides were shown to be homologous to a thaumatin
      like protein, showing high specificity to abiotic stress and to different
      reticuline oxidase-like proteins that displayed high levels of antifungal
      activity, suggesting that methyl jasmonate and cyclodextrins could play a role in
      mediating defense-related gene product expression in SCC of D. carota. Apart from
      these elicitor-inducible proteins, we observed the presence of PR-proteins in
      both control and elicited carrot SCC, suggesting that their expression is mainly
      constitutive. These PR-proteins are putative class IV chitinases, which also have
      inhibitory activity against pathogen growth and the class III peroxidases that
      participate in response to environmental stress (e.g. pathogen attack and
      oxidative), meaning that they are involved in defense responses triggered by both
      biotic and abiotic factors. 

PMID- 24589477
TI  - The improved resistance to high salinity induced by trehalose is associated with
      ionic regulation and osmotic adjustment in Catharanthus roseus.
AB  - The effects of exogenous trehalose (Tre) on salt tolerance of pharmaceutical
      plant Catharanthus roseus and the physiological mechanisms were both investigated
      in this study. The results showed that the supplement of Tre in saline condition
      (250 mM NaCl) largely alleviated the inhibitory effects of salinity on plant
      growth, namely biomass accumulation and total leaf area per plant. In this saline
      condition, the decreased level of relative water content (RWC) and photosynthetic
      rate were also greatly rescued by exogenous Tre. This improved performance of
      plants under high salinity induced by Tre could be partly ascribed to its ability
      to decrease accumulation of sodium, and increase potassium in leaves. The
      exogenous Tre led to high levels of fructose, glucose, sucrose and Tre inside the
      salt-stressed plants during whole the three-week treatment. The major free amino
      acids such as proline, arginine, threonine and glutamate were also largely
      elevated in the first two-week course of treatment with Tre in saline solution.
      It was proposed here that Tre might act as signal to make the salt-stressed
      plants actively increase internal compatible solutes, including soluble sugars
      and free amino acids, to control water loss, leaf gas exchange and ionic flow at
      the onset of salt stress. The application of Tre in saline condition also
      promoted the accumulation of alkaloids. The regulatory role of Tre in improving
      salt tolerance was optimal with an exogenous concentration of 10 mM Tre. Larger
      concentrations of Tre were supra-optimum and adversely affected plant growth. 

PMID- 24589478
TI  - Melatonin pretreatment prevented the effect of dexamethasone negative alterations
      on behavior and hippocampal neurogenesis in the mouse brain.
AB  - Glucocorticoids play various physiological functions via the glucocorticoid
      receptor (GR). Glucocorticoid is associated with the pathophysiology of
      depression. Dexamethasone (DEX), a synthetic GR agonist, has a greater affinity
      for GR than the mineralocorticoid receptor (MR) in the hippocampus of pigs and
      may mimic the effects of GR possession. DEX decreases neurogenesis and induces
      damage to hippocampal neurons that is associated with depressive-like behavior.
      Melatonin, a hormone mainly synthesized in the pineal gland, is a potent free
      radical scavenger and antioxidant. Melatonin alters noradrenergic transmission in
      depressed patients. It may be interesting to further explore the mechanism of
      melatonin that is associated with the role of stress as a key factor to
      precipitate depression and as a factor altering neurogenesis. In this study, we
      assessed the capability of melatonin to protect the hippocampus of mouse brains
      to counteract the effects of chronic DEX treatment for 21 days on depressive-like
      behavior and neurogenesis. Our results revealed that chronic administration of
      DEX induced depressive-like behavior and that this could be reversed by
      pretreatment with melatonin. Moreover, the number of 5-bromo-2-deoxyuridine
      (BrdU)-immunopositive cells and doublecortin (DCX; the neuronal-specific marker)
      protein levels were significantly reduced in the DEX-treated mice. Pretreatment
      with melatonin was found to renew BrdU and DCX expression in the dentate gyrus.
      Furthermore, pretreatment with melatonin prevented DEX-induced reductions in GR
      and an extracellular-signal-regulated kinase (ERK1/2) in the hippocampal area.
      Melatonin may protect hippocampal neurons from damage and reverse neurogenesis
      after chronic DEX by activating brain-derived neurotrophic (BDNF) and ERK1/2
      cascades. These results revealed that melatonin pretreatment prevented the
      reduction of cell proliferation, immature neuron precursor cells, and GR and
      ERK1/2 expression. This finding indicates that melatonin attenuates the DEX
      induced depressive-like behavior, supporting the notion that melatonin possesses
      anti-stress and neurogenic actions. 

PMID- 24589480
TI  - Chemokine (C-C motif) receptor 5 is an important pathological regulator in the
      development and maintenance of neuropathic pain.
AB  - BACKGROUND: The chemokine family has been revealed to be involved in the
      pathogenesis of neuropathic pain. In this study, the authors investigated the
      role of chemokine (C-C motif) ligand 3 and its receptors chemokine (C-C motif)
      receptor 1 and chemokine (C-C motif) receptor (CCR) 5 in neuropathic pain.
      METHODS: A spinal nerve injury model was established in adult male Wistar rats.
      The von Frey test and hot plate test were performed to evaluate neuropathic pain
      behavior, and real-time quantitative reverse transcription polymerase chain
      reaction, in situ hybridization, and immunohistochemistry were performed to
      understand the molecular mechanisms. RESULTS: The expression levels of chemokine
      (C-C motif) ligand 3 and CCR5 messenger RNA in the spinal cord were up-regulated
      after nerve injury, which was possibly due to CD11b-positive microglia. Single
      intrathecal administration of recombinant chemokine (C-C motif) ligand 3 produced
      biphasic tactile allodynia; each phase of pain behavior was induced by different
      receptors. Intrathecal injection of CCR5 antagonist suppressed the development of
      tactile allodynia (12.81 +/- 1.33 g vs. 3.52 +/- 0.41 g [mean +/- SEM, drug vs.
      control in paw-withdrawal threshold]; P < 0.05, n = 6 each) and could reverse
      established tactile allodynia (10.87 +/- 0.91 g vs. 3.43 +/- 0.28 g; P < 0.05, n
      = 8 and 7). Furthermore, Oral administration of CCR5 antagonist could reverse
      established tactile allodynia (8.20 +/- 1.27 g vs. 3.18 +/- 0.46 g; P < 0.05, n =
      4 each). CONCLUSIONS: Pharmacological blockade of CCR5 was effective in the
      treatment of the development and maintenance phases of neuropathic pain. Thus,
      CCR5 antagonists may be potential new drugs for the treatment of neuropathic
      pain.

PMID- 24589479
TI  - Evidence for the involvement of GD3 ganglioside in autophagosome formation and
      maturation.
AB  - Sphingolipids are structural lipid components of cell membranes, including
      membrane of organelles, such as mitochondria or endoplasmic reticulum, playing a
      role in signal transduction as well as in the transport and intermixing of cell
      membranes. Sphingolipid microdomains, also called lipid rafts, participate in
      several metabolic and catabolic cell processes, including apoptosis. However, the
      defined role of lipid rafts in the autophagic flux is still unknown. In the
      present study we analyzed the role of gangliosides, a class of sphingolipids, in
      autolysosome morphogenesis in human and murine primary fibroblasts by means of
      biochemical and analytical cytology methods. Upon induction of autophagy, by
      using amino acid deprivation as well as tunicamycin, we found that GD3
      ganglioside, considered as a paradigmatic raft constituent, actively contributed
      to the biogenesis and maturation of autophagic vacuoles. In particular,
      fluorescence resonance energy transfer (FRET) and coimmunoprecipitation analyses
      revealed that this ganglioside interacts with phosphatidylinositol 3-phosphate
      and can be detected in immature autophagosomes in association with LC3-II as well
      as in autolysosomes associated with LAMP1. Hence, it appears as a structural
      component of autophagic flux. Accordingly, we found that autophagy was
      significantly impaired by knocking down ST8SIA1/GD3 synthase (ST8 alpha-N-acetyl
      neuraminide alpha-2,8-sialyltransferase 1) or by altering sphingolipid metabolism
      with fumonisin B1. Interestingly, exogenous administration of GD3 ganglioside was
      capable of reactivating the autophagic process inhibited by fumonisin B1.
      Altogether, these results suggest that gangliosides, via their molecular
      interaction with autophagy-associated molecules, could be recruited to
      autophagosome and contribute to morphogenic remodeling, e.g., to changes of
      membrane curvature and fluidity, finally leading to mature autolysosome
      formation.

PMID- 24589482
TI  - Primary care team of the year: saving money and improving care.

PMID- 24589481
TI  - Disruption of hippocampal neuregulin 1-ErbB4 signaling contributes to the
      hippocampus-dependent cognitive impairment induced by isoflurane in aged mice.
AB  - BACKGROUND: A prolonged isoflurane exposure may lead to cognitive decline in
      rodents. Neuregulin 1 (NRG1)-ErbB4 signaling plays a key role in the modulation
      of hippocampal synaptic plasticity through regulating the neurotransmission. The
      authors hypothesized that hippocampal NRG1-ErbB4 signaling is involved in
      isoflurane-induced cognitive impairments in aged mice. METHODS: Fourteen-month
      old C57BL/6 mice were randomized to receive 100% O2 exposure, vehicle injection
      after 100% O2 exposure, vehicle injection after exposure to isoflurane carried by
      100% O2, NRG1-beta1 injection after exposure to isoflurane carried by 100% O2,
      and NRG1-beta1 and an ErbB4 inhibitor AG1478 injection after exposure to
      isoflurane carried by 100% O2. Fear conditioning test was used to assess the
      cognitive function of mice 48-h postexposure. The brain tissues were harvested 48
      h postexposure to determine the levels of NRG1, ErbB4, p-ErbB4, parvalbumin, and
      glutamic acid decarboxylase 67 in the hippocampus using Western blotting, enzyme
      linked immunosorbent assay, and immunofluorescence. RESULTS: The percentage of
      freezing time to context was decreased from 50.28 +/- 11.53% to 30.82 +/- 10.00%,
      and the hippocampal levels of NRG1, p-ErbB4/ErbB4, parvalbumin, and glutamic acid
      decarboxylase 67 were decreased from 172.79 +/- 20.85 ng/g, 69.15 +/- 12.20%,
      101.68 +/- 11.21%, and 104.71 +/- 6.85% to 112.92 +/- 16.65 ng/g, 42.26 +/-
      9.71%, 75.89 +/- 10.26%, and 73.87 +/- 16.89%, respectively, after isoflurane
      exposure. NRG1-beta1 attenuated the isoflurane-induced hippocampus-dependent
      cognitive impairment and the declines in the hippocampal NRG1, p-ErbB4/ErbB4,
      parvalbumin, and glutamic acid decarboxylase 67. AG1478 inhibited the rescuing
      effects of NRG1-beta1. CONCLUSION: Disruption of NRG1-ErbB4 signaling in the
      parvalbumin-positive interneurons might, at least partially, contribute to the
      isoflurane-induced hippocampus-dependent cognitive impairment after exposure to
      isoflurane carried by 100% O2 in aged mice.

PMID- 24589483
TI  - Sulfur rich 2-mercaptobenzothiazole and 1,2,3-triazole conjugates as novel
      antitubercular agents.
AB  - A series of benzfused heterocyclic derivatives such as amide conjugates of 2
      (benzo[d]thiazol-2-ylthio)acetic acid with aromatic/aliphatic/cyclic secondary
      amines (5a-5o & 8a-8m); 1,2,3-triazole conjugates of 2-mercaptobenzothiazoles and
      amide conjugates of indole-3-glyoxalic acid with cyclic secondary amines (14a
      14g) have been synthesized and were screened for their antitubercular activity
      against Mycobacterium tuberculosis H37Rv strain by broth microdilution assay
      method. Compounds 8b, 8f, 8g and 8l inhibited the growth of the H37Rv strain at
      concentrations of 8 MUg/mL. These compounds (8b, 8f, 8g and 8l) have been further
      identified as bactericidal and are completely killing the microbes at 32-64
      MUg/mL concentrations. Molecular docking studies of the active compounds reveal
      that these compounds are targeting DprE1 and may act as DprE1 inhibitors.

PMID- 24589484
TI  - 4-Functionalized 1,3-diarylpyrazoles bearing benzenesulfonamide moiety as
      selective potent inhibitors of the tumor associated carbonic anhydrase isoforms
      IX and XII.
AB  - A library of 4-functionalized 1,3-diarylpyrazoles (3a-3h, 5a-5g and 6a-6g) was
      designed, synthesized and evaluated against four human carbonic anhydrase (CA, EC
      4.2.1.1) isozymes representing two cytosolic isozymes hCA I and hCA II, and two
      transmembrane tumor associated ones, hCA IX and hCA XII. All the twenty two
      tested compounds exhibited excellent CA activity profile against the four CA
      isozymes when compared to the reference drug acetazolamide. Six of the tested
      compounds (3a-3b, 3f, 3h, 6a and 6b) displayed low nanomolar affinity (Ki < 5 nM)
      for hCA IX whereas seven compounds (3a-3b, 3d-3f, 3h and 6f) displayed Ki < 10 nM
      against hCA XII. In addition, they acted as selective CA inhibitors of isoforms
      IX and XII over the physiological isoforms I and II.

PMID- 24589486
TI  - Total synthesis of burkholdacs A and B and 5,6,20-tri-epi-burkholdac A: HDAC
      inhibition and antiproliferative activity.
AB  - The bicyclic depsipeptide histone deacetylase (HDAC) inhibitors burkholdacs A and
      B were efficiently synthesized in a highly convergent and unified manner. The
      synthesis features the amide coupling of a D-valine-D-cysteine- or D-allo
      isoleucine-D-cysteine-containing segment with a D-methionine-containing segment
      to directly assemble the corresponding seco-acids, key precursors for
      macrolactonization. Using the same methodology, 5,6,20-tri-epi-burkholdac A was
      also synthesized. HDAC inhibitory assays and cell-growth inhibition analyses of
      the synthesized depsipeptides demonstrated the potency order of this class of
      bicyclic depsipeptides as compared to the clinically approved depsipeptide FK228
      (romidepsin). Novel structure-activity relationships within this class of
      compounds were also revealed.

PMID- 24589485
TI  - Synthesis and evaluation of (-)-Massoialactone and analogues as potential
      anticancer and anti-inflammatory agents.
AB  - (-)-Massoialactone, an alpha,beta-unsaturated delta-lactone isolated from
      Cryptocarya massoia, and five analogues were synthesized and their
      antiproliferative and anti-inflammatory activities were evaluated. The lactones
      were able to mimic the "core" functional group required for the biological
      activity of their parent natural compounds suggesting that substantially altered
      analogues may retain their properties. 

PMID- 24589487
TI  - Design, synthesis and evaluation of genistein-O-alkylbenzylamines as potential
      multifunctional agents for the treatment of Alzheimer's disease.
AB  - A series of genistein derivatives with carbon spacer-linked alkylbenzylamines
      were designed, synthesized and tested as multifunctional agents for the treatment
      of Alzheimer's disease (AD). The results showed that most of these compounds
      exhibited good acetylcholinesterase (AChE) inhibitory activity, with moderate-to
      good anti-oxidative activity. Specifically, compounds 10b, 19d and 25d exhibited
      significant inhibition of beta-amyloid (Abeta) aggregation and exhibited metal
      chelating properties. In particular, 25d inhibited: self-induced Abeta1-42
      aggregation, Cu(2+)-induced Abeta1-42 aggregation, and human AChE-induced Abeta1
      40 aggregation by 35%, 77.8%, and 36.2%, respectively. Moreover, both kinetic
      analysis of AChE inhibition and the molecular modeling study suggested that 25d
      binds simultaneously to catalytic active site and peripheral anionic site of
      AChE. More importantly, compound 25d disassembled the well-structured Abeta
      fibrils generated by Cu(2+)-induced Abeta aggregation by 72.1%. Furthermore, the
      step-down passive avoidance test showed this compound significantly reversed
      scopolamine-induced memory deficit in mice. These results suggest that 25d may be
      a promising multifunctional agent for AD treatment.

PMID- 24589488
TI  - New enantiomeric fluorine-containing derivatives of sulforaphane: synthesis,
      absolute configurations and biological activity.
AB  - Three pairs of enantiomers of the unknown sulforaphane analogs bearing
      organofluorine substituents bonded to the sulfinyl sulfur atom and having
      different number of methylene groups in the central carbon chain were synthesized
      and fully characterized, including determination of their absolute
      configurations. All the new compounds were tested in vitro for their cytotoxicity
      against melanoma cells to show increased activity in comparison with the natural
      sulforaphane. The influence of the particular structural changes in the molecule
      on the cytotoxicity is discussed.

PMID- 24589489
TI  - Benzamidobenzoic acids as potent PqsD inhibitors for the treatment of Pseudomonas
      aeruginosa infections.
AB  - Targeting PqsD is a promising novel approach to disrupt bacterial cell-to-cell
      communication in Pseudomonas aeruginosa. In search of selective PqsD inhibitors,
      two series of benzamidobenzoic acids - one published as RNAP inhibitors and the
      other as PqsD inhibitors - were investigated for inhibitory activity toward the
      respective other enzyme. Additionally, novel derivatives were synthesized and
      biologically evaluated. By this means, the structural features needed for
      benzamidobenzoic acids to be potent and, most notably, selective PqsD inhibitors
      were identified. The most interesting compound of this study was the 3-Cl
      substituted compound 5 which strongly inhibits PqsD (IC50 6.2 MUM) while
      exhibiting no inhibition of RNAP.

PMID- 24589490
TI  - Predictive QSAR modeling of aldose reductase inhibitors using Monte Carlo feature
      selection.
AB  - This study explores the chemical space and quantitative structure-activity
      relationship (QSAR) of a set of 60 sulfonylpyridazinones with aldose reductase
      inhibitory activity. The physicochemical properties of the investigated compounds
      were described by a total of 3230 descriptors comprising of 6 quantum chemical
      descriptors and 3224 molecular descriptors. A subset of 5 descriptors was
      selected from the aforementioned pool by means of Monte Carlo (MC) feature
      selection coupled to multiple linear regression (MLR). Predictive QSAR models
      were then constructed by MLR, support vector machine and artificial neural
      network, which afforded good predictive performance as deduced from internal and
      external validation. The investigated models are capable of accounting for the
      origins of aldose reductase inhibitory activity and could be utilized in
      predicting this property in screening for novel and robust compounds. 

PMID- 24589491
TI  - Evaluation of novel trans-sulfonamide platinum complexes against tumor cell
      lines.
AB  - Platinum-based drugs, mainly cisplatin, are employed for the treatment of solid
      malignancies. However, cisplatin treatment often results in the development of
      chemoresistance, leading to therapeutic failure. Here, the antitumor activity of
      different trans-sulfonamide platinum complexes in a panel of human cell lines is
      presented. The cytotoxicity profiles and cell cycle analyses of these platinum
      sulfonamide complexes were different from those of cisplatin. These studies
      showed that complex 2b with cyclohexyldiamine and dansyl moieties had the best
      antitumoral activities. 

PMID- 24589492
TI  - From sensation to percept: the neural signature of auditory event-related
      potentials.
AB  - An external auditory stimulus induces an auditory sensation which may lead to a
      conscious auditory perception. Although the sensory aspect is well known, it is
      still a question how an auditory stimulus results in an individual's conscious
      percept. To unravel the uncertainties concerning the neural correlates of a
      conscious auditory percept, event-related potentials may serve as a useful tool.
      In the current review we mainly wanted to shed light on the perceptual aspects of
      auditory processing and therefore we mainly focused on the auditory late-latency
      responses. Moreover, there is increasing evidence that perception is an active
      process in which the brain searches for the information it expects to be present,
      suggesting that auditory perception requires the presence of both bottom-up, i.e.
      sensory and top-down, i.e. prediction-driven processing. Therefore, the auditory
      evoked potentials will be interpreted in the context of the Bayesian brain model,
      in which the brain predicts which information it expects and when this will
      happen. The internal representation of the auditory environment will be verified
      by sensation samples of the environment (P50, N100). When this incoming
      information violates the expectation, it will induce the emission of a prediction
      error signal (Mismatch Negativity), activating higher-order neural networks and
      inducing the update of prior internal representations of the environment (P300). 

PMID- 24589493
TI  - Task-relevance dependent gradients in medial prefrontal and temporoparietal
      cortices suggest solutions to paradoxes concerning self/other control.
AB  - Contrary to the prevailing view, Nicolle and colleagues (2012) recently
      demonstrated that dorsal and ventral regions of the medial prefrontal cortex
      (mPFC) and temporoparietal cortex (TPC) do not distinguish between action values
      relating to the self and to another individual; rather, these regions
      differentiate whether an action is currently relevant or irrelevant to the task
      at hand. This finding suggests solutions to paradoxes in social cognition. The
      first paradox concerns self/other control: With some experimental tasks TPC
      activity is associated with the promotion of self over other representations; in
      different tasks the association is with other over self (Santiesteban et al.,
      2012a). The second paradox concerns the control of imitation: MPFC has been
      associated with both the facilitation and inhibition of imitation. Considering
      task-relevance (i.e. whether the participant's task is to respond according to
      their own action values or to respond as if they were another individual)
      suggests possible solutions to these paradoxes. 

PMID- 24589495
TI  - Disintegration in the biogas sector--technologies and effects.
AB  - Pretreatment of organic material prior to anaerobic digestion is seen as an
      option to increase the overall efficiency of the process. An overview of
      physical, chemical, and biological disintegration (DT) of substrates in the
      biogas sector is given. The energy demands DT were surveyed. The technologies
      were evaluated by reference to the Technology Readiness Assessment Guide of the
      U.S. Department of Energy. The evaluation focuses on ligno-cellulosic substrates
      like straw. Data of a survey among biogas plant operators were analyzed regarding
      the prevalence of disintegration technology classes in Germany. Furthermore,
      biochemical methane potential tests were conducted in laboratory scale to
      determine the specific methane yields of un-/treated barley straw (thermal
      pressure hydrolysis (TPH)). A methane potential of 228 ml CH4/g VS was measured
      for untreated barley straw; and of 251 ml CH4/g VS for TPH-straw (190  degrees C,
      30 min). The reaction rates in BMP were calculated between 0.0976 and 0.1443 d(
      1).

PMID- 24589496
TI  - In brief: testosterone and cardiovascular risk.

PMID- 24589497
TI  - Riociguat (Adempas) for pulmonary hypertension.

PMID- 24589494
TI  - The translational apparatus of plastids and its role in plant development.
AB  - Chloroplasts (plastids) possess a genome and their own machinery to express it.
      Translation in plastids occurs on bacterial-type 70S ribosomes utilizing a set of
      tRNAs that is entirely encoded in the plastid genome. In recent years, the
      components of the chloroplast translational apparatus have been intensely studied
      by proteomic approaches and by reverse genetics in the model systems tobacco
      (plastid-encoded components) and Arabidopsis (nucleus-encoded components). This
      work has provided important new insights into the structure, function, and
      biogenesis of chloroplast ribosomes, and also has shed fresh light on the
      molecular mechanisms of the translation process in plastids. In addition, mutants
      affected in plastid translation have yielded strong genetic evidence for
      chloroplast genes and gene products influencing plant development at various
      levels, presumably via retrograde signaling pathway(s). In this review, we
      describe recent progress with the functional analysis of components of the
      chloroplast translational machinery and discuss the currently available evidence
      that supports a significant impact of plastid translational activity on plant
      anatomy and morphology. 

PMID- 24589498
TI  - Low dose diclofenac (Zorvolex) for pain.

PMID- 24589499
TI  - Does Pathogen Identification Influence the Clinical Outcomes in Patients With
      Pyogenic Spinal Infections?
AB  - STUDY DESIGN: Retrospective study. OBJECTIVE: To study the clinical outcomes of
      patients suffering from pyogenic spinal infections (PSI), by comparing the
      outcomes of patients with an identified microbiological agent with those of
      patients without an identified pathogen. SUMMARY OF BACKGROUND DATA: PSI is
      associated with significant risks for morbidity and mortality. Specific
      antibiotic treatment has been considered a key to successful medical treatment;
      however, clinicians frequently treat patients with PSI without an identified
      agent. A paucity of data is available comparing the clinical outcomes of patients
      with or without an identified pathogen. MATERIALS AND METHODS: The records of 97
      consecutive patients discharged from a University Hospital with the diagnosis of
      PSI during a 14-year period were retrospectively reviewed. Patients'
      demographics, etiological agent, comorbidities, site of infection, white blood
      cell count, erythrocyte sedimentation rate, C-reactive protein at the time of
      presentation, neurological impairment, length of hospital stay, and mortality
      were registered to compare the clinical outcomes of patients with an identified
      pathogen with those of patients without an identified agent. RESULTS: The
      causative organism was identified in 74 patients (76.3%). Patients with
      microbiological diagnosis were younger, and a larger percentage of them exhibited
      elevated C-reactive protein value; however, they were not different from those
      without an identified agent in terms of sex, site of infection, comorbidities,
      and the presence of a concomitant infection. Our study could not demonstrate
      different neurological outcomes, length of stay, or mortality rates among the 2
      groups. CONCLUSIONS: In a large series of patients with PSI, we did not
      demonstrate differences in clinical outcomes using empirical antibiotics in
      patients without an identified pathogen compared with patients with an identified
      microbiological agent receiving specific antibiotics. Future prospective
      multicenter studies should be conducted to obtain an answer to this important
      clinical question.

PMID- 24589500
TI  - Reduction in lesions from Lmax: a new concept for assessing efficacy of field
      directed therapy for actinic keratosis. Results with imiquimod 3.75%.
AB  - BACKGROUND: Current parameters for assessing the efficacy of actinic keratosis
      (AK) treatments compare clinical lesions at the start and end of a study.
      However, the sun-exposed field also contains subclinical lesions which may become
      detectable during treatment. Lmax, the maximum lesion count during treatment, is
      a new concept to better assess the efficacy of field-directed AK therapies.
      Measuring efficacy using the reduction in lesions from Lmax includes for the
      first time the clearance of both subclinical and clinical lesions. OBJECTIVES: To
      evaluate the reduction of lesions from Lmax to study end and compare the results
      with traditional efficacy endpoints using imiquimod 3.75% (IQ3.75%) as an example
      of field-directed AK therapy. MATERIALS & METHODS: Pooled analysis of data from
      two 14-week, vehicle-controlled, double-blind studies of IQ3.75%. RESULTS: With
      IQ3.75%, the median number of lesions increased from 10 at baseline to an Lmax of
      22. The median absolute reduction in lesions to study end was 18 from Lmax versus
      7 from baseline. The median percentage reduction in AK lesions to study end was
      92.2% from Lmax compared with 81.8% from baseline. CONCLUSIONS: The reduction in
      lesion count from Lmax is a novel efficacy parameter that should become the new
      way of evaluating field-directed AK therapies since it enables their efficacy
      against both clinical and subclinical lesions to be accurately determined.
      Together, the Lmax concept and IQ3.75% represent a new approach for the
      management of AK across a large sun-exposed field.

PMID- 24589502
TI  - Electrochemical reduction of CO2 in organic solvents catalyzed by MoO2.
AB  - MoO2 microparticles act as an active catalyst for the electrochemical reduction
      of CO2 in organic solvents such as acetonitrile and dimethylformamide. The
      catalytic activity and product selectivity depend on temperature and water
      content of the solvent. 

PMID- 24589501
TI  - Divergence of East Asians and Europeans estimated using male- and female-specific
      genetic markers.
AB  - To study the male and female lineages of East Asian and European humans, we have
      sequenced 25 short tandem repeat markers on 453 Y-chromosomes and collected
      sequences of 72 complete mitochondrial genomes to construct independent
      phylogenetic trees for male and female lineages. The results indicate that East
      Asian individuals fall into two clades, one that includes East Asian individuals
      only and a second that contains East Asian and European individuals.
      Surprisingly, the European individuals did not form an independent clade, but
      branched within in the East Asians. We then estimated the divergence time of the
      root of the European clade as ~ 41,000 years ago. These data indicate that,
      contrary to traditional views, Europeans diverged from East Asians around that
      time. We also address the origin of the Ainu lineage in northern Japan.

PMID- 24589503
TI  - Health status and bioremediation capacity of wild freshwater mussels (Diplodon
      chilensis) exposed to sewage water pollution in a glacial Patagonian lake.
AB  - Deleterious effects on health and fitness are expected in mussels chronically
      exposed to sewage water pollution. Diplodon chilensis inhabiting SMA, an area
      affected by untreated and treated sewage water, shows increased hemocyte number
      and phagocytic activity, while bacteriolytic and phenoloxidase activities in
      plasma and reactive oxygen species production in hemocytes are lower compared to
      mussels from an unpolluted area (Yuco). There are not differences in cell
      viability, lysosomal membrane stability, lipid peroxidation and total oxygen
      scavenging capacity between SMA and Yuco mussels' hemocytes. Energetic reserves
      and digestive gland mass do not show differences between groups; although the
      condition factor is higher in SMA than in Yuco mussels. Gills of SMA mussels show
      an increase in mass and micronuclei frequency compared to those of Yuco. Mussels
      from both sites reduce bacterial loads in polluted water and sediments, improving
      their quality with similar feeding performance. These findings suggest that
      mussels exposed to sewage pollution modulate physiological responses by long-term
      exposure; although, gills are sensitive to these conditions and suffer chronic
      damage. Bioremediation potential found in D. chilensis widens the field of work
      for remediation of sewage bacterial pollution in water and sediments by filtering
      bivalves. 

PMID- 24589504
TI  - Doubly TEMPO-coordinated gadolinium(III), lanthanum(III), and yttrium(III)
      complexes. Strong superexchange coupling across rare earth ions.
AB  - We prepared crystalline [RE(III)(hfac)3(TEMPO)2] (RE = Gd, La, Y), where TEMPO
      and hfac stand for 2,2,6,6-tetramethylpiperidin-1-oxyl and 1,1,1,5,5,5
      hexafluoropentane-2,4-dionate, respectively. The X-ray crystal structure of TEMPO
      coordinated RE compounds was determined for the first time. The Gd and Y
      analogues are isomorphous, and the La derivative has a similar molecular
      skeleton. The Gd-O(TEMPO) bond lengths were 2.322(3) and 2.354(3) A with the O-Gd
      O angle of 140.36(11) degrees . The magnetic study clarified that
      [Gd(hfac)3(TEMPO)2] behaved as a ground Stotal = 7/2 species. The La and Y
      analogues showed the superexchange interactions across the diamagnetic ions with
      2JTEMPO1-TEMPO2/kB = -14.9(1) and -49.8(2) K, respectively. Assuming the presence
      of a similar interaction like the Y derivative, the Gd-TEMPO exchange couplings
      are estimated with 2JGd-TEMPO/kB = -12.9(5) and +8.0(6) K. 

PMID- 24589505
TI  - Predicting first-year mortality in incident dialysis patients with end-stage
      renal disease - the UREA5 study.
AB  - We aimed to develop a risk prediction model for first-year mortality (FYM) in
      incident dialysis patients with end-stage renal disease. We retrospectively
      examined patient comorbidities and biochemistry, prior to dialysis initiation,
      using a single-center, prospectively maintained database from 2005-2010, and
      analyzed these variables in relation to FYM. A total of 983 patients were
      studied. 22% had left ventricular ejection fraction (LVEF) <45%. FYM was 17%, and
      independent predictors included URate <500 or >600 MUmol/l, LVEF <45% (higher
      odds ratio if <30%), Age >70 years, Arteriopathies (cerebrovascular and/or
      peripheral-vascular diseases), serum Albumin <30 g/l, and Alkaline phosphatase
      >80 U/l (p < 0.05, C-statistic 0.74), and these constitute the acronym UREA5.
      Using linear modeling, risk weightage/integer of 3 was assigned to LVEF <30%, 2
      to age >70 years, and 1 to each remaining variable. Cumulative UREA5 scores of <=
      1, 2, 3, 4, and >= 5 were associated with FYM of 6, 8, 22, 31, and 46%,
      respectively (p < 0.0001). Increasing UREA5 scores were strongly associated with
      stepwise worsening of FYM after dialysis initiation.

PMID- 24589506
TI  - Regenerative implants for cardiovascular tissue engineering.
AB  - A fundamental problem that affects the field of cardiovascular surgery is the
      paucity of autologous tissue available for surgical reconstructive procedures.
      Although the best results are obtained when an individual's own tissues are used
      for surgical repair, this is often not possible as a result of pathology of
      autologous tissues or lack of a compatible replacement source from the body. The
      use of prosthetics is a popular solution to overcome shortage of autologous
      tissue, but implantation of these devices comes with an array of additional
      problems and complications related to biocompatibility. Transplantation offers
      another option that is widely used but complicated by problems related to
      rejection and donor organ scarcity. The field of tissue engineering represents a
      promising new option for replacement surgical procedures. Throughout the years,
      intensive interdisciplinary, translational research into cardiovascular
      regenerative implants has been undertaken in an effort to improve surgical
      outcome and better quality of life for patients with cardiovascular defects.
      Vascular, valvular, and heart tissue repair are the focus of these efforts.
      Implants for these neotissues can be divided into 2 groups: biologic and
      synthetic. These materials are used to facilitate the delivery of cells or drugs
      to diseased, damaged, or absent tissue. Furthermore, they can function as a
      tissue-forming device used to enhance the body's own repair mechanisms. Various
      preclinical studies and clinical trials using these advances have shown that
      tissue-engineered materials are a viable option for surgical repair, but require
      refinement if they are going to reach their clinical potential. With the growth
      and accomplishments this field has already achieved, meeting those goals in the
      future should be attainable.

PMID- 24589507
TI  - Metastatic malignant melanoma: computed tomography-guided 125I seed implantation
      treatment.
AB  - The aim of this study is to evaluate the therapeutic efficacy of computed
      tomography (CT)-guided interstitial iodine-125 (I) seed implantation for
      metastatic malignant melanoma treatment. From November 2008 to May 2011, 24
      patients with metastatic malignant melanoma who had undergone surgery for
      excision of primary lesions and repeated chemotherapy underwent CT-guided I seed
      implantation. Their clinical situations, biochemical indicators, MRIs, and CTs
      were observed. The follow-up time ranged from 5 to 24 months (mean 19.6 months).
      The local control rates of metastatic malignant melanoma after surgery excision
      for primary lesion after 2, 6, 12, and 24 months were 86.8, 78.6, 62.1, and
      55.0%, respectively. One patient died of liver failure 5 months after
      brachytherapy and another died of a metastatic brain tumor 8 months after
      brachytherapy. Two patients died of lung dysfunction from pulmonary metastases 15
      months after brachytherapy. All other patients survived throughout the follow-up
      period. The 2-year survival rate was 83.3%. During the procedure, one patient
      presented with minimal bleeding from the applicator route and another presented
      with pneumothorax with 20% pulmonary compression, which improved after
      intraprocedure suctioning. Four patients had low-grade fever on day 3. Three
      showed mild decreases in their white blood cell counts. CT-guided I seed
      implantation is a safe, feasible, and promising approach to the treatment of
      patients with metastatic malignant melanoma after surgery excision for primary
      lesions and repeated chemotherapy, but large-scale randomized clinical trials
      should be conducted before the technique can be used routinely. 

PMID- 24589509
TI  - An in-depth pilot study on patterns, destinations, and purposes of walking in
      Hong Kong older adults.
AB  - Walking is a suitable activity for older adults and has physical and mental
      health benefits. To devise interventions that impact levels of walking it is
      necessary to first understand the purposes for which people walk and the
      destinations to which they walk. Using a 7-day diary and accelerometry, this
      study investigated destinations and purposes of walking in older adult residents
      of an ultra-dense Asian city. Participants reported an average of 17.1 walking
      trips per week and total weekly accelerometer/diary determined trip walking time
      averaged 735 min per week; much higher than reported for older adults in non
      Asian settings. The most common destinations were within the neighborhood: parks
      and streets for recreation walking and shops and eating places for transport
      related walking. Errands and eating were the most common purposes for
      transportation trips. The study results can help inform urban design to encourage
      walking. 

PMID- 24589508
TI  - Phosphorylation-mediated regulation of GEFs for RhoA.
AB  - Spatio-temporal control of RhoA GTPase is critical for regulation of cell
      migration, attachment to extracellular matrix, and cell-cell adhesions.
      Activation of RhoA is mediated by guanine nucleotide exchange factors (GEFs), a
      diverse family of enzymes that are controlled by multiple signaling pathways
      regulating actin cytoskeleton and cell migration. GEFs can be regulated by
      different mechanisms. Growing evidence demonstrates that phosphorylation serves
      as one of the predominant signals controlling activity, interactions, and
      localization of RhoGEFs. It acts as a positive and a negative regulator, and
      allows for regulation of RhoGEFs by multiple signaling cascades. Although there
      are common trends in phosphorylation-mediated regulation of some RhoGEF homologs,
      the majority of GEFs utilize distinct mechanisms that are dictated by their
      unique structure and interaction networks. This diversity enables multiple
      signaling pathways to use different RhoGEFs for regulation of a single central
      RhoA. Here, we review current examples of phosphorylation-mediated regulation of
      GEFs for RhoA and its role in cell migration, discuss mechanisms, and provide
      insights into potential future directions.

PMID- 24589510
TI  - Heat stroke burn: unusual cutaneous damage due to heat wave.

PMID- 24589511
TI  - Synthesis and carbonic anhydrase I, II, IX and XII inhibition studies of 4-N,N
      disubstituted sulfanilamides incorporating 4,4,4-trifluoro-3-oxo-but-1-enyl,
      phenacylthiourea and imidazol-2(3H)-one/thione moieties.
AB  - A series of sulfonamides incorporating the sulfanilamide (SA) scaffold were
      prepared. Reaction of the 4-amino moiety of SA with benzyl chlorides or
      substituted bromoacetophenones afforded the 4-mono-alkylated derivatives which
      were then reacted with 1,1,1-trifluoro-4-isobutoxybut-3-en-2-one leading to a
      series of 4-N,N-disubstituted SAs. The key intermediates were also reacted with
      ethoxycarbonyl isothiocyanate leading to thioureas or were cyclized in the
      presence of potassium cyanate/isothiocyanate to the corresponding imidazol-2(3H)
      one/thiones. The new compounds were tested as inhibitors of four carbonic
      anhydrase (CA, EC 4.2.1.1) isoforms, the cytosolic CA I and II, and the
      transmembrane, tumor-associated CA IX and XII. These sulfonamides were
      ineffective CA I and II inhibitors but were nanomolar CA IX and XII inhibitors,
      making them of interest as clinical candidates for antitumor/antimetastasis
      applications. 

PMID- 24589512
TI  - Plastic behaviors in hosts promote the emergence of retaliatory parasites.
AB  - Mafia like behavior, where individuals cooperate under the threat of punishment,
      occurs not only in humans, but is also observed in several animal species.
      Observations suggest that avian hosts tend to accept a certain degree of
      parasitism in order to avoid retaliating punishment from the brood parasite. To
      understand under which conditions it will be beneficial for a host to cooperate,
      we model the interaction between hosts and parasites as an evolutionary game. In
      our model, the host's behavior is plastic, and thus, its response depends on the
      previous interactions with the parasite. We find that such learned behavior in
      turn is crucial for the evolution of retaliating parasites. The abundance of this
      kind of mafia behavior oscillates in time and does not settle to an equilibrium.
      Our results suggest that retaliation is a mechanism for the parasite to evade
      specialization and to induce acceptance by the host. 

PMID- 24589513
TI  - A phenomenological expression to describe the temperature dependence of pressure
      induced softening in negative thermal expansion materials.
AB  - By exploring a simple model of a negative thermal expansion (NTE) system, we
      introduce a phenomenological expression to describe the temperature dependence of
      the pressure-induced softening in NTE structures. 

PMID- 24589514
TI  - Simultaneous rapid sequencing of multiple RNA virus genomes.
AB  - Comparing sequences of archived viruses collected over many years to the present
      allows the study of viral evolution and contributes to the design of new
      vaccines. However, the difficulty, time and expense of generating full-length
      sequences individually from each archived sample have hampered these studies.
      Next generation sequencing technologies have been utilized for analysis of
      clinical and environmental samples to identify viral pathogens that may be
      present. This has led to the discovery of many new, uncharacterized viruses from
      a number of viral families. Use of these sequencing technologies would be
      advantageous in examining viral evolution. In this study, a sequencing procedure
      was used to sequence simultaneously and rapidly multiple archived samples using a
      single standard protocol. This procedure utilized primers composed of 20 bases of
      known sequence with 8 random bases at the 3'-end that also served as an
      identifying barcode that allowed the differentiation each viral library following
      pooling and sequencing. This conferred sequence independence by random priming
      both first and second strand cDNA synthesis. Viral stocks were treated with a
      nuclease cocktail to reduce the presence of host nucleic acids. Viral RNA was
      extracted, followed by single tube random-primed double-stranded cDNA synthesis.
      The resultant cDNAs were amplified by primer-specific PCR, pooled, size
      fractionated and sequenced on the Ion Torrent PGM platform. The individual virus
      genomes were readily assembled by both de novo and template-assisted assembly
      methods. This procedure consistently resulted in near full length, if not full
      length, genomic sequences and was used to sequence multiple bovine pestivirus and
      coronavirus isolates simultaneously. 

PMID- 24589515
TI  - Direct detection of human herpesvirus 6B by the LAMP method using newly developed
      dry-reagents.
AB  - The reliability of the HHV-6B LAMP using the dry-reagent method was evaluated
      using serum samples obtained from febrile children. The sensitivity of the
      original and dry-reagent methods was 10 copies/reaction and 100 copies/reaction,
      respectively. The dry-reagent LAMP method was highly sensitive (94.0%) and
      specific (96.0%) for the detection of HHV-6B. 

PMID- 24589516
TI  - Generation and evaluation of avian leukosis virus subgroup J envelope
      glycoprotein recombinant pseudovirions.
AB  - Retroviral and lentiviral vector pseudotypes (based on human immunodeficiency
      virus type 1, HIV-1) have been used for stable and safe gene transfer because of
      their broad host ranges and high mechanical strength. In the present study, a
      recombinant avian leukosis virus subgroup J (ALV-J) polypeptide pseudotyped with
      lentivirus membrane glycoproteins gp85 and gp37, HIV/env-ALV, was generated,
      characterized in vitro and evaluated for its ability to infect natural host
      cells. We optimized the newly developed micro-neutralization (MN) assay using
      recombinant pseudovirion HIV/env-ALV expressing enhanced green fluorescent
      protein and well-characterized sera from chickens with confirmed ALV-J disease or
      virus-free controls. HIV/env-ALV could infect CEF and DF-1 but not pk15, 293FT,
      MDCK or VERO E6 cells, therefore demonstrating a cellular tropism similar to the
      wild-type ALV-J. The MN assay indicated that the IC50 values of positive sera
      offered a considerable advantage in both speed and accuracy. These results
      suggest that this pseudotyped lentivirus is a good model for studying the
      functions of ALV-J env and that the MN assay is a reliable serological method for
      assessing antibody levels in investigating the actual status of the current ALV-J
      epidemic. These recombinant pseudovirions may prove to be useful for studying ALV
      J biology in lower biosafety level laboratory environments, and also for the
      detection and quantification of neutralizing antibodies to ALV-J in a manner akin
      to ELISA assays, but that would also be applicable to other viruses. 

PMID- 24589517
TI  - Treatment of postburn ear defect with expanded upper arm flap and consequent
      expansion without skin grafting.
AB  - Total ear reconstruction in the postburn auricle is one of the most challenging
      procedures for plastic surgeons. Adverse factors associated with these procedures
      include reduced or damaged blood supply, poor elasticity of scar tissue,
      increased risk of infection, and the possible destruction of skin,
      temporoparietal fascia, or retroauricular fascia. In cases where patients are
      severely burned, free flaps, such as radial forearm flaps, contralateral
      temporoparietal fascial flaps, or omental flaps, can be used as framework
      envelopes. In this work, we introduced a novel method of expanded upper arm flap
      transfer, followed by an expansion method of total ear reconstruction without
      skin grafting. 

PMID- 24589518
TI  - Coeliac disease.

PMID- 24589519
TI  - Direct measurement of internal magnetic fields in natural sands using scanning
      SQUID microscopy.
AB  - NMR experiments are ideally carried out in well-controlled magnetic fields. When
      samples of natural porous materials are studied, the situation can be complicated
      if the sample itself contains magnetic components, giving rise to internal
      magnetic fields in the pore space that modulate the externally applied fields. If
      not properly accounted for, the internal fields can lead to misinterpretation of
      relaxation, diffusion, or imaging data. To predict the potential effect of
      internal fields, and develop effective mitigation strategies, it is important to
      develop a quantitative understanding of the magnitude and distribution of
      internal fields occurring in natural porous media. To develop such understanding,
      we employ scanning SQUID microscopy, a technique that can detect magnetic field
      variations very accurately at high spatial resolution (~3MUm). We prepared
      samples from natural unconsolidated aquifer material, and scanned areas of about
      200*200MUm in a very low background magnetic field of ~2MUT. We found large
      amplitude variations with a magnitude of about 2mT, across a relatively long
      spatial scale of about 200MUm, that are associated with a large magnetic grain
      (>50MUm radius) with a strong magnetic remanence. We also detected substantial
      variations exceeding 60MUT on small spatial scales of about ~10MUm. We attribute
      these small-scale variations to very fine-grained magnetic material. Because we
      made our measurements at very low background field, the observed variations are
      not induced by the background field but due to magnetic remanence. Consequently,
      the observed internal fields will affect even low-field NMR experiments. 

PMID- 24589520
TI  - Untangling the influences of unmodeled evolutionary processes on phylogenetic
      signal in a forensically important HIV-1 transmission cluster.
AB  - Stochastic models of sequence evolution have been developed to reflect many
      biologically important processes, allowing for accurate phylogenetic
      reconstruction when an appropriate model is selected. However, commonly used
      models do not incorporate several potentially important biological processes.
      Spurious phylogenetic inference may result if these processes play an important
      role in the evolution of a dataset yet are not incorporated into assumed models.
      Few studies have attempted to assess the relative importance of multiple
      processes in producing spurious inferences. The application of phylogenetic
      methods to infer the source of HIV-1 transmission clusters depends upon accurate
      phylogenetic results, yet there are several relevant unmodeled biological
      processes (e.g., recombination and convergence) that may cause complications.
      Here, through analyses of HIV-1 env sequences from a small, forensically
      important transmission cluster, we tease apart the impact of these processes and
      present evidence suggesting that convergent evolution and high rates of
      insertions and deletions (causing alignment uncertainty) led to spurious
      phylogenetic signal with forensic relevance. Previous analyses show paraphyly of
      HIV-1 lineages sampled from an individual who, based on non-phylogenetic
      evidence, had never acted as a source of infection for others in this
      transmission cluster. If true, this pattern calls into question assumptions
      underlying phylogenetic approaches to source and recipient identification. By
      systematically assessing the contribution of different unmodeled processes, we
      demonstrate that removal of sites likely influenced by strong positive selection
      both reduces the alignment-wide signal supporting paraphyly of viruses sampled
      from this individual and eliminates support for the effects of recombination.
      Additionally, the removal of ambiguously aligned sites alters strongly supported
      relationships among viruses sampled from different individuals. These
      observations highlight the need to jointly consider multiple unmodeled
      evolutionary processes and motivate a phylogenomic perspective when inferring
      viral transmission histories. 

PMID- 24589521
TI  - Cellular localization and dendritic function of rat isoforms of the SRF
      coactivator MKL1 in cortical neurons.
AB  - The ability of megakaryoblastic leukemia 1 (MKL1) to function as a serum response
      factor (SRF) coactivator is regulated through its association with G-actin. In
      the cytoplasm, MKL1 binds to G-actin through RPXXXEL (RPEL) motifs. However,
      dissociation of MKL1 from G-actin triggers its translocation into the nucleus
      where it stimulates SRF-mediated gene expression. Previous characterization of
      rat MKL1 gene products has identified several isoforms: full-length MKL1, basic,
      SAP, and coiled-coil domain (BSAC), MKL1-elongated derivative of yield (MELODY),
      and MKL1met. In this study, we have investigated whether these MKL1 isoforms,
      which contain different numbers of RPEL motifs, differ in their subcellular
      localization, transcriptional activity, and effect on dendritic number and axonal
      length. Immunofluorescent staining of cultured cortical neurons expressing
      individual FLAG-tagged MKL1 isoforms indicated that all MKL1 isoforms are present
      in both the cytoplasm and the nucleus. However, MKL1met, which contains two RPEL
      motifs, shows enhanced nuclear staining compared with the other three isoforms,
      full-length MKL1, basic, SAP, and coiled-coil domain, and MKL1-elongated
      derivative of yield, which contain three RPEL motifs. Consistent with its
      preferential nuclear localization, overexpression of MKL1met, but not other
      isoforms, increases SRF-mediated transcriptional responses and reduces the number
      of dendrites. In contrast to the inhibitory effect of MKL1met on dendritic
      number, axonal length is not affected by overexpression of any of the MKL1
      isoforms. These findings suggest that the subcellular localization of MKL1
      isoforms, which is mediated by the number of actin-binding RPEL motifs, regulates
      their effect on SRF-mediated gene expression and dendritic morphology. 

PMID- 24589522
TI  - Microbiota of the seminal fluid.

PMID- 24589523
TI  - Reply of the authors.

PMID- 24589524
TI  - The therapeutic role of fulvestrant in the management of patients with hormone
      receptor-positive breast cancer.
AB  - Although selective estrogen receptor modulators (SERMs), such as tamoxifen, or
      aromatase inhibitors (AIs), such as anastrozole, are the preferred endocrine
      treatment approach for most patients with hormone receptor-positive breast
      cancer, many patients progress despite this therapy or become resistant.
      Fulvestrant is a selective estrogen receptor down-regulator (SERD) that has
      demonstrated activity and efficacy in patients with hormone receptor-positive
      breast cancer previously untreated or treated with hormonal therapy. The efficacy
      of fulvestrant has been demonstrated in the neoadjuvant and metastatic settings,
      either alone or in combination with other therapies such as anastrozole or
      targeted drugs. Additionally, 500 mg of fulvestrant have been shown to be more
      effective than 250 mg, without significant differences in the toxicity profile.
      In this review, the unique mode of action of fulvestrant and the clinical data
      for different dosing regimens both alone or in combination with other drugs is
      critically assessed. 

PMID- 24589525
TI  - Instruments to assess mobility limitation in community-dwelling older adults: a
      systematic review.
AB  - Mobility is critical in maintaining independence in older adults. This study aims
      to systematically review the scientific literature to identify measures of
      mobility limitation for community-dwelling older adults. A systematic search of
      PubMed, CINAHL, and psycINFO, using the search terms "mobility limitation",
      "mobility disability", and "mobility difficulty" yielded 1,847 articles from 1990
      to 2012; a final selection of 103 articles was used for the present manuscript.
      Tools to measure mobility were found to be either self-report or performance
      based instruments. Commonly measured constructs of mobility included walking,
      climbing stairs, and lower extremity function. There was heterogeneity in ways of
      defining and measuring mobility limitation in older adults living in the
      community. Given the lack of consistency in assessment tools for mobility, a
      clear understanding and standardization of instruments are required for
      comparison across studies and for better understanding indicators and outcomes of
      mobility limitation in community-dwelling older adults. 

PMID- 24589526
TI  - Mean platelet volume variation after biologic therapy in psoriasis and psoriatic
      arthritis.

PMID- 24589527
TI  - Cluster expansion of multicomponent ionic systems with controlled accuracy:
      importance of long-range interactions in heterovalent ionic systems.
AB  - We have been examining factors determining the accuracy of cluster expansion
      (CE), which is used in combination with many density functional theory (DFT)
      calculations. With the exception of multicomponent metallic or isovalent ionic
      systems, the contributions of long-range effective cluster interactions (ECIs) to
      configurational energetics are not negligible, which is ascribed to long-range
      electrostatic interactions. The truncation of ECIs in such systems leads to
      systematic errors. A typical problem with such errors can be seen in Monte Carlo
      simulations, since simulation supercells composed of a larger number of atoms
      than those of the input DFT structures are used. The prediction errors for long
      period structures beyond the cell size of the input DFT structures in addition to
      those for short-period structures within the cell size of the input DFT
      structures need to be carefully examined to control the accuracy of CE. In this
      study, we quantitatively discuss the contribution of the truncation of long-range
      ECIs to the accuracy of CE. Two types of system, namely a point-charge spinel
      lattice and a real MgAl2O4 spinel crystal, are examined. The prediction error of
      the long-period structures can be improved both by increasing the number of pairs
      and by also considering the effective screened electrostatic energy. 

PMID- 24589528
TI  - Rate of bubble coalescence following quasi-static approach: screening and
      neutralization of the electric double layer.
AB  - Air-bubble coalescence in aqueous electrolytic solutions, following quasi-static
      approach, was studied in order to understand its slow rate in purified water and
      high rate in electrolytic solutions. The former is found to be due to surface
      charges, originating from the speciation of dissolved CO2, which sustain the
      electric double layer repulsion. Rapid coalescence in electrolytic solutions is
      shown to occur via two different mechanisms: (1) neutralization of the
      carbonaceous, charged species by acids; or (2) screening of the repulsive charge
      effects by salts and bases. The results do not indicate any ion specificity. They
      can be explained within the DLVO theory for the van der Waals and electric double
      layer interactions between particles, in contrast to observations of coalescence
      following dynamic approach. The present conclusions should serve as a reference
      point to understanding the dynamic behavior. 

PMID- 24589529
TI  - Validation of the Thermor BIOS BD215 device for home blood pressure measurement
      according to the European Society of Hypertension International Protocol revision
      2010.
AB  - The objective of this study was to determine the accuracy of the Thermor BIOS
      BD215 device for home blood pressure (BP) measurement according to the
      International Protocol of the European Society of Hypertension (ESH). Device
      evaluation was carried out in 33 patients. The mean age of the patients was 57.0
      +/- 15.0 years, the mean systolic BP was 142.0 +/- 20.3 mmHg (range 100-177
      mmHg), the mean diastolic BP was 88.0 +/- 14.6 mmHg (range 48-123 mmHg), and the
      mean arm circumference was 28.0 +/- 3.0 cm (range 24-33 cm). The protocol
      requirements were followed precisely. The device passed all requirements,
      fulfilling the standards of the protocol. On average, the device overestimated
      the systolic BP by 0.6 +/- 4.2 mmHg and underestimated diastolic BP by -0.5 +/-
      3.2 mmHg. The device-observer discrepancies were unrelated to patients' clinical
      characteristics. These data show that the Thermor BIOS BD215 device fulfilled the
      requirements for validation by the International Protocol and can be recommended
      for clinical use in the adult population.

PMID- 24589530
TI  - The synthesis, characterization, antimicrobial and antimutagenic activities of
      hydroxyphenylimino ligands and their metal complexes of usnic acid isolated from
      Usnea longissima.
AB  - Novel multifunctional hydroxyphenylimino ligands (L1, L2 and L3) were synthesized
      by the condensation of 2-aminophenol, 3-aminophenol and 4-aminophenol with usnic
      acid, a lichen metabolite. The synthesized ligands and their Cu(II), Co(II),
      Ni(II) and Mn(II) complexes were characterized using FT-IR, UV-Vis, (1)H-NMR,
      (13)C-NMR, 1D- and 2D NMR (DEPT, COSY, HMQC and HMBC), LC-MS and TGA. In
      addition, the metal complexes of the novel ligands were prepared with high yields
      using Cu(II), Co(II), Ni(II) and Mn(II) salts and were characterized using the FT
      MIR/FAR, UV-Vis, elemental analysis, ICP-OES and TG/DTA techniques. The ligands
      and their complexes were tested against ten important pathogen microorganisms
      using the disc diffusion method and the metal complexes of the ligands were more
      active against all of the microorganisms tested with a broad spectrum than the
      ligands exhibiting 11-32 mm inhibition zones. On the other hand, a broad spectrum
      of the strongest antimicrobial activity was determined for the Mn(II) and Cu(II)
      complexes of the hydroxyphenylimino ligand with usnic acid (L3). In addition, the
      antimutagenic activities of all of the ligands and their metal complexes were
      determined using the Ames-Salmonella and E. coli WP2 microbial assay systems and
      they showed varied and strong antimutagenic effects. In general, it has been
      found that the Co and Mn complexes of the ligands possess potent antimutagenic
      activity. In view of these results, it can be concluded that some metal complexes
      can be used as antimicrobial and anticancer agents.

PMID- 24589531
TI  - Efficient synthesis strategies by application of transition metal-catalyzed
      carbene/nitrene insertions into C-H bonds.
AB  - Transition metal-catalyzed insertion of carbenes and nitrenes into C-H bonds has
      become a powerful tool for the construction of C-C and C-N bonds in the synthesis
      of complex natural products. In this Highlight, a selection of syntheses are
      detailed involving the implementation of C-H insertion reactions leading to
      strategies marked by improved efficiency.

PMID- 24589532
TI  - More information emerging on NSAIDs' potential cardiovascular risks.

PMID- 24589533
TI  - ICU infection-prevention efforts could be better, study finds.

PMID- 24589534
TI  - Stakeholders discuss biosimilar naming, substitution.

PMID- 24589535
TI  - Tips for a successful poster presentation.

PMID- 24589536
TI  - Ruxolitinib for the treatment of primary myelofibrosis.
AB  - PURPOSE: The pharmacology, pharmacokinetics, pharmacogenomics, clinical efficacy,
      and safety profile of ruxolitinib for the treatment of primary myelofibrosis are
      reviewed. SUMMARY: Ruxolitinib, an oral tyrosine kinase inhibitor that targets
      the Janus-associated kinases (JAKs) 1 and 2, has been recently approved for the
      treatment of patients with intermediate- or high-risk myelofibrosis. Unlike
      previous treatment options for patients with myelofibrosis, ruxolitinib offers a
      targeted therapy option for these patients who often suffer with severe and
      debilitating symptoms associated with the disease process. After oral
      administration, ruxolitinib is rapidly absorbed and can be given without regard
      to meals. Ruxolitinib is primarily metabolized by the cytochrome P-450 (CYP) 3A4
      isoenzyme system; therefore, if concomitant use with a strong CYP3A4 inhibitor is
      unavoidable, an initial dosage reduction is warranted. Two Phase III randomized
      trials comparing ruxolitinib to either placebo or best available therapy found a
      rapid and sustained response in the reduction of spleen size and improvements in
      constitutional symptoms and quality of life, with one study demonstrating an
      improvement in overall survival. The most commonly reported serious adverse
      effects of ruxolitinib are anemia and thrombocytopenia. Ruxolitinib is
      administered as an oral tablet given twice daily, with the initial starting
      dosage based on the baseline platelet count. Dosage reductions are based on the
      development of thrombocytopenia. CONCLUSION: By directly targeting both JAK1 and
      JAK2 through small-molecule inhibition, ruxolitinib elicits a reduction in
      splenomegaly and disease-related symptoms in patients with intermediate- or high
      risk myelofibrosis while maintaining an acceptable toxicity profile and a low
      treatment-discontinuation rate.

PMID- 24589537
TI  - Integrated clinical and specialty pharmacy practice model for management of
      patients with multiple sclerosis.
AB  - PURPOSE: An integrated clinical and specialty pharmacy practice model for the
      management of patients with multiple sclerosis (MS) is described. SUMMARY:
      Specialty medications, such as disease-modifying therapies (DMTs) used to treat
      MS, are costly and typically require special administration, handling, and
      storage. DMTs are associated with high rates of nonadherence and may have
      associated safety risks. The University of Illinois Hospital and Health Sciences
      System developed an MS pharmacy practice model that sought to address the many
      challenges of coordinating care with multiple entities outside the health system.
      Several key features of the integrated model include a dedicated clinical
      pharmacist on the MS specialty team, an integrated specialty pharmacy service,
      direct access to the electronic medical record, and face-to-face interaction with
      patients. Through the active involvement of the neurology clinical pharmacist and
      an onsite specialty pharmacy service, targeted assessments and medication and
      disease education are provided to the patient before DMT initiation and
      maintained throughout therapy. In addition, the regular point of contact and
      refill coordination encourages improved compliance, appropriate medication use,
      ongoing safety monitoring, and improved communication with the provider for
      quicker interventions. This fosters increased accessibility, convenience, and
      patient confidence. Improving patient outcomes--the priority goal of this service
      model--will be assessed in future planned studies. Through this new practice
      model, providers are empowered to incorporate specialty medication management
      into transitions in care, admission and discharge quality indicators,
      readmissions, and other core measures. CONCLUSION: An integrated pharmacy
      practice model that includes an interdisciplinary team of physicians, nurses, and
      pharmacists improved patient compliance with MS therapies.

PMID- 24589538
TI  - Cost-minimization analysis of two fluid products for resuscitation of critically
      injured trauma patients.
AB  - PURPOSE: Results of a study to determine potential cost benefits of substituting
      an alternative electrolyte solution for 0.9% sodium chloride injection for the
      initial fluid resuscitation of trauma patients are presented. METHODS: Using data
      from a randomized clinical trial that compared 24-hour fluid resuscitation
      outcomes in critically injured trauma patients treated with 0.9% sodium chloride
      injection and those who received a balanced electrolyte solution (Plasma-Lyte A,
      Baxter Healthcare), a cost-minimization analysis was performed at a large medical
      center. The outcomes evaluated included fluid and drug acquisition costs,
      materials and nurse labor costs, and costs associated with electrolyte
      replacement. RESULTS: The use of Plasma-Lyte A was associated with a relatively
      higher fluid acquisition cost but a reduced need for magnesium replacement.
      During the first 24 hours of hospitalization, 4 of 24 patients (17%) treated with
      0.9% sodium chloride injection and none of the patients who received the
      comparator product (n = 22) required supplemental magnesium. Patients treated
      with 0.9% sodium chloride injection received a median of 4 g of magnesium
      (interquartile range [IQR], 2.5-4.0 g), compared with a median of 0 g (IQR 0-2 g)
      in the comparator group. Taking into account the costs of consumable supplies and
      nursing labor, the cost-minimization analysis indicated a 24-hour cost
      differential of $12.35 in favor of Plasma-Lyte A. CONCLUSION: Substitution of
      Plasma-Lyte A for 0.9% sodium chloride injection for fluid resuscitation during
      the first 24 hours after traumatic injury was associated with decreased magnesium
      replacement requirements and a net cost benefit to the institution.

PMID- 24589539
TI  - Aseptic simulation test for cytotoxic drug production in isolators.
AB  - PURPOSE: The results of a media-fill test (MFT) study to validate processes for
      cytotoxic drug preparation inside and outside aseptic compounding isolators are
      presented. METHODS: Using an MFT protocol adapted to institution-specific
      production conditions, the pharmacy team at a hospital in France performed a
      series of tests to verify the efficacy of decontamination and sterile compounding
      procedures, as required by French compendial standards, while assessing the
      performance of its team of 12 isolator operators; all operators were tested on
      three occasions, producing 10 MFT samples per test for a total of 30 samples per
      operator. The team also tested alternative compounding systems (i.e., two closed
      system transfer devices and a classic spike system) for use during power outages
      or other emergencies precluding drug preparation within isolators. MFTs were
      performed using a standard tryptone soy broth-based test kit under worst-case
      conditions. RESULTS: The hospital's facilities for cytotoxic drug preparation
      were found to be in conformance with applicable sterility standards. Bacterial
      growth was not detected in any of the MFT samples produced by isolator operators
      during the study (total n = 360). In one instance, an MFT sample prepared using a
      closed-system transfer device was found to be contaminated due to improper
      cleaning of the medication vial, highlighting the importance of strict adherence
      to proper decontamination procedures. CONCLUSION: A hospital's practices for
      preparation of sterile products according to applicable good manufacturing
      guidelines, as well as emergency procedures for cytotoxic drug preparation
      outside isolators, were validated by the results of an MFT study.

PMID- 24589540
TI  - National trends in prescription drug expenditures and projections for 2014.
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 2014. METHODS: Trends in pharmaceutical expenditures and developments
      likely to influence future spending, including new drug approvals and patent
      expirations, were analyzed using data from the IMS Health National Sales
      Perspectives database. Projections were based on a combination of quantitative
      and qualitative analyses and expert opinion. RESULTS: Total prescription sales
      for the 12 months ending September 2013 were approximately $326 billion, 0.7%
      lower than sales during the previous 12 months; pharmaceutical spending by
      clinics and nonfederal hospitals grew by 4.5% and 1.8%, respectively. Vaccines
      were among the products driving large sales increases in clinic settings, with
      alteplase and pegfilgrastim topping the list of fast-growing drugs by hospital
      expenditures. Few new drug approvals anticipated in 2014 are expected to result
      in major expenditures by hospitals and clinics. Expansion of access to health
      care and other changes related to the Patient Protection and Affordable Care Act,
      as well as continued improvement in the U.S. economy, may drive growth in
      pharmaceutical spending over the next 12-24 months. CONCLUSION: Growth in U.S.
      prescription drug expenditures is expected to rebound in 2014, with a projected 3
      5% increase in total drug expenditures across all settings this year, including a
      5-7% increase in clinic spending and a 1-3% increase in hospital spending. Health
      system pharmacy leaders should carefully examine local drug-utilization patterns
      to determine their respective organization's anticipated spending in 2014.

PMID- 24589541
TI  - Evidence to support use of palonosetron over generic serotonin type 3-receptor
      antagonists for chemotherapy-induced nausea and vomiting.

PMID- 24589542
TI  - Serotonin type 3-receptor antagonists for chemotherapy-induced nausea and
      vomiting: therapeutically equivalent or meaningfully different?

PMID- 24589543
TI  - CuO/CuSCN valence state heterojunctions with visible light enhanced and
      ultraviolet light restrained photocatalytic activity.
AB  - CuSCN is applied, for the first time, in a photocatalytic system to form
      CuO/CuSCN valence state heterojunctions, which exhibited enhanced visible light
      driven photocatalytic activity and, surprisingly, ultraviolet light restrained
      activity. Proper migration of photo-generated carriers is proposed to explain the
      photocatalytic process. 

PMID- 24589544
TI  - Iron-catalyzed carbonylative Suzuki reactions under atmospheric pressure of
      carbon monoxide.
AB  - The first highly effective iron-catalyzed carbonylative Suzuki reaction has been
      developed. Substrates with electron-donating or electron-withdrawing
      functionality, ortho-substitution, as well as active groups proceeded smoothly,
      affording desired products in high yields. This protocol is economical,
      environmentally benign and practical for the synthesis of biaryl ketones. 

PMID- 24589545
TI  - Sleep fragmentation and false memories during pregnancy and motherhood.
AB  - Pregnant women, both before and after childbirth, frequently experience memory
      deficits and disrupted sleep. In the present study we assessed the relationship
      between false memory generation and fragmented sleep during pregnancy and
      motherhood. We tested 178 pregnant women and 58 female non-pregnant childless
      controls, during pregnancy (15-35th week of gestation) and again after childbirth
      (8-13th month). False memories were defined as memories of gist words that were
      semantically related to studied word lists but were not presented during learning
      of these lists in the Deese-Roediger-McDermott (DRM) paradigm. Sleep was
      monitored by actigraphy in the home environment for seven consecutive nights.
      Compared to the controls, the group of pregnant women produced more false
      memories and displayed more fragmented sleep both during pregnancy and after
      childbirth. However, false memory generation was not correlated to measures of
      sleep fragmentation. These results show that pregnant women suffer from sleep
      fragmentation and a higher susceptibility to false memories, but leave open the
      question as to whether both phenomena are related. 

PMID- 24589546
TI  - Bone marrow mononuclear cell transplantation promotes therapeutic angiogenesis
      via upregulation of the VEGF-VEGFR2 signaling pathway in a rat model of vascular
      dementia.
AB  - Bone marrow mononuclear cells (BMMNCs) are important for angiogenesis after
      stroke. We investigated the effects of BMMNCs on cognitive function,
      angiogenesis, and the vascular endothelial growth factor (VEGF)-VEGF receptor 2
      (VEGFR2) signaling pathway in a rat model of vascular dementia. We transplanted
      BMMNCs into rats that had undergone permanent bilateral occlusion of the common
      carotid arteries (2VO) and observed their migration in vivo. On day 28, we
      assessed cognitive function with the Morris Water Maze test and examined vascular
      density and white matter damage within the corpus striatum by staining with
      fluorescein lycopersicon esculentum (tomato) lectin or Luxol fast blue. We
      evaluated expression of VEGF, rapidly accelerated fibrosarcoma 1 (Raf1), and
      extracellular-signal-regulated kinases 1 and 2 (ERK1/2) in the ischemic
      hemisphere by Western blot analysis on day 7 after cell transplantation.
      Contribution of the VEGF-VEGFR2 signaling pathway was confirmed by using VEGFR2
      inhibitor SU5416. BMMNCs penetrated the blood-brain barrier and reached the
      ischemic cortex and white matter or incorporated into vascular walls of 2VO rats.
      BMMNC-treated 2VO rats had better learning and memory, higher vascular density,
      and less white matter damage than did vehicle-treated rats. The beneficial
      effects of BMMNCs were abolished by pretreatment of rats with SU5416. Protein
      expression of VEGF and phosphorylated Raf1 and ERK1/2 was also significantly
      increased by BMMNC treatment, but this upregulation was reversed by SU5416.
      BMMNCs can enhance angiogenesis, reduce white matter damage, and promote
      cognitive recovery in 2VO rats. The angiogenic effect may result from
      upregulation of the VEGF-VEGFR2 signaling pathway. 

PMID- 24589547
TI  - Repeated maternal intramuscular or intraamniotic erythromycin incompletely
      resolves intrauterine Ureaplasma parvum infection in a sheep model of pregnancy.
AB  - OBJECTIVE: Ureaplasma spp are the most commonly isolated microorganisms in
      association with preterm birth. Maternal erythromycin administration is a
      standard treatment for preterm prelabor rupture of membranes. There is little
      evidence of its effectiveness in eradicating Ureaplasma spp from the intrauterine
      cavity and fetus. We used a sheep model of intrauterine Ureaplasma spp infection
      to investigate the efficacy of repeated maternal intramuscular and intraamniotic
      erythromycin treatment to eradicate such an infection. STUDY DESIGN: Thirty ewes
      with singleton pregnancies received an intraamniotic injection of 10(7) color
      change units of erythromycin-sensitive Ureaplasma parvum serovar 3 at 55 days'
      gestation. At 116 days' gestation, 28 ewes with viable fetuses were randomized to
      receive (1) intraamniotic and maternal intramuscular saline solution treatment (n
      = 8), (2) single intraamniotic and repeated maternal intramuscular erythromycin
      treatment (n = 10), or (3) single maternal intramuscular and repeated
      intraamniotic erythromycin treatment (n = 10). Fetuses were surgically delivered
      at 125 days' gestation. Treatment efficacy was assessed by culture, quantitative
      polymerase chain reaction, and histopathologic evaluation. RESULTS: Animals
      treated with intraamniotic erythromycin had significantly less viable U parvum
      serovar 3 in the amniotic fluid at delivery. However, neither combination of
      maternal intramuscular and intraamniotic erythromycin treatment successfully
      cleared U parvum serovar 3 from the amniotic fluid or fetal tissues. Three de
      novo erythromycin-resistant U parvum isolates were identified in erythromycin
      treated animals. CONCLUSION: Erythromycin treatment, given both to the ewe and
      into the amniotic cavity, fails to eradicate intrauterine and fetal U parvum
      serovar 3 infection and may lead to development of erythromycin resistant U
      parvum.

PMID- 24589548
TI  - Perinatal mortality in second- vs firstborn twins: a matter of birth size or
      birth order?
AB  - OBJECTIVE: Second-born twins on average weigh less than first-born twins and have
      been reported at an elevated risk of perinatal mortality. Whether the risk
      differences depend on their relative birth size is unknown. The present study
      aimed to evaluate the association of birth order with perinatal mortality by
      birth order-specific weight difference in twin pregnancies. STUDY DESIGN: In a
      retrospective cohort study of 258,800 twin pregnancies without reported
      congenital anomalies using the US matched multiple birth data 1995-2000 (the
      available largest multiple birth dataset), conditional logistic regression was
      applied to estimate the odds ratio (OR) of perinatal death adjusted for fetus
      specific characteristics (sex, presentation, and birthweight for gestational
      age). RESULTS: Comparing second vs first twins, the risks of perinatal death were
      similar if they had similar birthweights (within 5%) and were increasingly higher
      if second twins weighed progressively less (adjusted ORs were 1.37, 1.90, and
      3.94 if weighed 5.0-14.9%, 15.0-24.9%, and >=25.0% less, respectively), and
      progressively lower if they weighed increasingly more (adjusted ORs were 0.67,
      0.63, and 0.36 if weighed 5.0-14.9%, 15.0-24.9%, and >=25.0% more, respectively)
      (all P < .001). The perinatal mortality rates were not significantly different in
      cesarean deliveries or preterm (<37 weeks) vaginal deliveries but were
      significantly higher in second twins in term vaginal deliveries (3.1 vs 1.8 per
      1000; adjusted OR, 2.15; P < .001). CONCLUSION: Perinatal mortality risk
      differences in second vs first twins depend on their relative birth size. Vaginal
      delivery at term is associated with a substantially greater risk of perinatal
      mortality in second twins.

PMID- 24589549
TI  - Dynamic of bone marrow fibrosis regression predicts survival after allogeneic
      stem cell transplantation for myelofibrosis.
AB  - We correlate regression of bone marrow fibrosis (BMF) on day 30 and 100 after
      dose- reduced allogeneic stem cell transplantation (allo-SCT) in 57 patients with
      primary or post-essential thrombocythemia/polycythemia vera myelofibrosis with
      graft function and survival. The distribution of International Prognostic Scoring
      System (IPSS) risk score categories was 1 patient with low risk, 5 patients with
      intermediate-1 risk, 18 patients with intermediate-2 risk, and 33 patients with
      high risk. Before allo-SCT, 41 patients (72%) were classified as XXX
      [myclofibrosis (MF)]-3 and 16 (28%) were classified as MF-2 according to the
      World Health Organization criteria. At postengraftment day +30 (+/-10 days), 21%
      of the patients had near-complete or complete regression of BMF (MF-0/-1), and on
      day +100 (+/-20 days), 54% were MF-0/-1. The 5-year overall survival rate at day
      +100 was 96% in patients with MF-0/-1 and 57% for those with MF-2/-3 (P = .04).
      There was no difference in BMF regression at day +100 between IPSS high-risk and
      low/intermediate-risk patients. Complete donor cell chimerism at day +100 was
      seen in 81% of patients with MF-0/-1 and in 31% of those with MF-2/-3. Patients
      with MF-2/-3 at day +100 were more likely to be transfusion-dependent for either
      RBCs (P = .014) or platelets (P = .018). Rapid BMF regression after reduced
      intensity conditioning allo-SCT resulted in a favorable survival independent of
      IPSS risk score at transplantation.

PMID- 24589550
TI  - The plant stigma exudate: a biochemically active extracellular environment for
      pollen germination?
AB  - During sexual reproduction, pollen performance is greatly influenced by the
      female tissues. The stigma exudate, i.e., the extracellular secretion that covers
      the stigma outermost surface, has been usually regarded as a reservoir of water,
      secondary metabolites, cell wall precursors and compounds that serve as energy
      supply for rapid pollen tube growth. In an attempt to identify the proteins
      present in the stigma secretome, we performed a large-scale analysis in two
      species (Lilium longiflorum and Olea europaea) following a proteomic-based
      approach. The resulting data strongly suggest that the stigma exudate is not a
      mere storage site but also a biochemically active environment with a markedly
      catabolic nature. Thus, this secretion may modulate early pollen tube growth and
      contribute to the senescence of stigma after pollination. In addition, a putative
      cross-talk between genetic programs that regulate stress/defense and pollination
      responses in the stigma is also suggested. The stigma exudate might also
      functionally diverge between species on the basis on their ecology and the
      biochemical, morphological and anatomical features of their stigmas.
      Unexpectedly, we identified in both exudates some intracellular proteins,
      suggesting that a mechanism other than the canonical ER-Golgi exocytic pathway
      may exist in the stigma and contribute to exudate secretion. 

PMID- 24589551
TI  - Molecular basis underlying histone H3 lysine-arginine methylation pattern readout
      by Spin/Ssty repeats of Spindlin1.
AB  - Histone modification patterns and their combinatorial readout have emerged as a
      fundamental mechanism for epigenetic regulation. Here we characterized Spindlin1
      as a histone effector that senses a cis-tail histone H3 methylation pattern
      involving trimethyllysine 4 (H3K4me3) and asymmetric dimethylarginine 8
      (H3R8me2a) marks. Spindlin1 consists of triple tudor-like Spin/Ssty repeats.
      Cocrystal structure determination established concurrent recognition of H3K4me3
      and H3R8me2a by Spin/Ssty repeats 2 and 1, respectively. Both H3K4me3 and
      H3R8me2a are recognized using an "insertion cavity" recognition mode,
      contributing to a methylation state-specific layer of regulation. In vivo
      functional studies suggest that Spindlin1 activates Wnt/beta-catenin signaling
      downstream from protein arginine methyltransferase 2 (PRMT2) and the MLL complex,
      which together are capable of generating a specific H3 "K4me3-R8me2a" pattern.
      Mutagenesis of Spindlin1 reader pockets impairs activation of Wnt target genes.
      Taken together, our work connects a histone "lysine-arginine" methylation pattern
      readout by Spindlin1-to-Wnt signaling at the transcriptional level. 

PMID- 24589552
TI  - Meiosis-specific cohesin mediates homolog recognition in mouse spermatocytes.
AB  - During meiosis, homologous chromosome (homolog) pairing is promoted by several
      layers of regulation that include dynamic chromosome movement and meiotic
      recombination. However, the way in which homologs recognize each other remains a
      fundamental issue in chromosome biology. Here, we show that homolog recognition
      or association initiates upon entry into meiotic prophase before axis assembly
      and double-strand break (DSB) formation. This homolog association develops into
      tight pairing only during or after axis formation. Intriguingly, the ability to
      recognize homologs is retained in Sun1 knockout spermatocytes, in which telomere
      directed chromosome movement is abolished, and this is the case even in Spo11
      knockout spermatocytes, in which DSB-dependent DNA homology search is absent.
      Disruption of meiosis-specific cohesin RAD21L precludes the initial association
      of homologs as well as the subsequent pairing in spermatocytes. These findings
      suggest the intriguing possibility that homolog recognition is achieved primarily
      by searching for homology in the chromosome architecture as defined by meiosis
      specific cohesin rather than in the DNA sequence itself. 

PMID- 24589554
TI  - Folliculotropic mycosis fungoides with extreme pilosebaceous involvement and
      hematological abnormalities.

PMID- 24589553
TI  - Diminished WNT -> beta-catenin -> c-MYC signaling is a barrier for malignant
      progression of BRAFV600E-induced lung tumors.
AB  - Oncogene-induced senescence (OIS) is proposed as a cellular defense mechanism
      that restrains malignant progression of oncogene-expressing, initiated tumor
      cells. Consistent with this, expression of BRAF(V600E) in the mouse lung
      epithelium elicits benign tumors that fail to progress to cancer due to an
      apparent senescence-like proliferative arrest. Here we demonstrate that nuclear
      beta-catenin -> c-MYC signaling is essential for early stage proliferation of
      BRAF(V600E)-induced lung tumors and is inactivated in the subsequent senescence
      like state. Furthermore, either beta-catenin silencing or pharmacological
      blockade of Porcupine, an acyl-transferase essential for WNT ligand secretion and
      activity, significantly inhibited BRAF(V600E)-initiated lung tumorigenesis.
      Conversely, sustained activity of beta-catenin or c-MYC significantly enhanced
      BRAF(V600E)-induced lung tumorigenesis and rescued the anti-tumor effects of
      Porcupine blockade. These data indicate that early stage BRAF(V600E)-induced lung
      tumors are WNT-dependent and suggest that inactivation of WNT -> beta-catenin ->
      c-MYC signaling is a trigger for the senescence-like proliferative arrest that
      constrains the expansion and malignant progression of BRAF(V600E)-initiated lung
      tumors. Moreover, these data further suggest that the trigger for OIS in
      initiated BRAF(V600E)-expressing lung tumor cells is not simply a surfeit of
      signals from oncogenic BRAF but an insufficiency of WNT -> beta-catenin -> c-MYC
      signaling. These data have implications for understanding how genetic
      abnormalities cooperate to initiate and promote lung carcinogenesis. 

PMID- 24589555
TI  - Idiopathic hypertrophic pachymeningitis: clinical, laboratory and neuroradiologic
      features in China.
AB  - Hypertrophic pachymeningitis is a rare chronic inflammatory disorder
      characterized by marked fibrous thickening of the cerebral and/or spinal dura
      mater. Clinical, laboratory, neuroradiologic and therapeutic data from 12
      patients with idiopathic hypertrophic pachymeningitis (IHP) from our department
      were retrospectively studied. There were four men and eight women with a mean age
      of 49+/-15.3 years, and more than half of the patients (58%) were aged 40-60
      years. Headache was the most common symptom, occurring in 92% of patients.
      Headache improved markedly and rapidly after glucocorticoid treatment. Optic
      nerve involvement was noted in seven patients (58%). C-reactive protein levels
      increased in 80% and the erythrocyte sedimentation rate increased in 71% of
      patients. Three patients were positive for autoantibodies, including antinuclear
      antibodies (ANA), perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCA),
      anti-cardiolipin antibodies (ACA) and rheumatoid factor (RF). Cerebrospinal fluid
      showed inflammatory changes, and protein levels were low to moderately elevated.
      MRI revealed a thickened dura in all patients, and five patients (42%) were
      diagnosed with sinus stenosis/occlusion. IHP is a chronic inflammatory disorder
      of the dura with three groups of symptoms, namely headache, cranial nerve palsy
      and symptoms due to sinus stenosis/occlusion. However, IHP has different features
      in China in that it predominantly affects women and the age of onset is younger.
      Sinus stenosis/occlusion is relatively common in IHP patients in China.

PMID- 24589556
TI  - Arg972 insulin receptor substrate-1 polymorphism and risk and severity of
      Alzheimer's disease.
AB  - We explored the association between the Arg972 insulin receptor substrate-1
      (IRS1) polymorphism and the risk and severity of Alzheimer's disease (AD). We
      genotyped the Arg972 IRS1 (rs1801278) polymorphism in 1123 pairs of age, sex,
      body mass index, residence area and education level-matched Han Chinese AD
      patients and controls. AD severity was assessed with Mini-Mental State
      Examination (MMSE) scores. The AA (homozygous Arg972 IRS1) and GA (heterozygous
      Arg972 IRS1) genotypes were associated with an increased risk of AD after
      adjustment for comorbidities including type 2 diabetes mellitus, coronary heart
      disease, and hypertension (p<0.001; adjusted odds ratio [OR] 3.93 and 2.90,
      respectively). The A allele was associated with an increased risk of AD after
      adjustment for comorbidities (p<0.001; adjusted OR 2.26; 95% confidence interval
      1.92-2.80). The percentage of Arg972 IRS1 AA homozygotes was higher in the MMSE
      score ?14 category than in the MMSE score 15-26 category overall and in each age
      group (p<0.001), while the wild type IRS1 GG homozygotes were predominantly found
      in the MMSE score 15-26 category overall and in each age group. The GG homozygote
      group had higher MMSE score than the GA heterozygote group, which in turn had
      higher MMSE score than the AA homozygote group overall and in each age group
      (p<0.05). In conclusion, the Arg972 IRS1 polymorphism is an independent risk
      factor for AD and the A allele has a gene dosage effect on AD severity in Han
      Chinese. This study adds fresh insights into the pathogenesis of AD. 

PMID- 24589557
TI  - Primary Hodgkin lymphoma of the central nervous system.
AB  - Primary involvement of the central nervous system by Hodgkin lymphoma is rare;
      most cases represent metastases. We report a primary Hodgkin lymphoma presenting
      in the cerebellum of a 77-year-old man and review the literature on primary
      Hodgkin lymphoma of the central nervous system. 

PMID- 24589558
TI  - Simple exercise test score versus cardiac stress test for the prediction of
      coronary artery disease in patients with type 2 diabetes.
AB  - INTRODUCTION: Type 2 diabetes markedly increases the risk of coronary heart
      disease (CHD), and screening for CHD is suggested by the guidelines. OBJECTIVES:
      The aim of the study was to compare the diagnostic usefulness of the simple
      exercise test score, incorporating the clinical data and cardiac stress test
      results, with the standard stress test in patients with type 2 diabetes. PATIENTS
      AND METHODS: A total of 62 consecutive patients (aged 65.4 +/-8.5 years; 32 men)
      with type 2 diabetes and clinical symptoms suggesting CHD underwent a stress test
      followed by coronary angiography. The simple score was calculated for all
      patients. RESULTS: Significant coronary stenosis was observed in 41 patients
      (66.1%). Stress test results were positive in 36 patients (58.1%). The mean
      simple score was high (65.5 +/-14.3 points). A positive linear relationship was
      observed between the score and the prevalence of CHD (R2 = 0.19; P <0.001) as
      well as its severity (R2 = 0.23; P <0.001). The area under the receiver-operating
      characteristic curve for the simple score was 0.74 (95% confidence interval [CI],
      0.62-0.86). At the original cut-off value of 60 points, the score had a similar
      prognostic value to that of the standard stress test. However, in a multivariate
      analysis, only the simple score (odds ratio [OR], 1.46; 95% CI, 1.11-1.94; P
      <0.01 for an increase in the score by 1 point) and male sex (OR, 1.57; 95% CI,
      1.24-1.98; P <0.001) remained independent predictors of CHD. CONCLUSIONS: In
      patients with type 2 diabetes, the simple score correlated with the prevalence
      and severity of CHD. However, the cut-off value of 60 points was inadequate in
      the population of diabetic patients with high risk of CHD. The simple score used
      instead of or together with the stress test was a better predictor of CHD than
      the stress test alone.

PMID- 24589559
TI  - Exercise intensities of gardening tasks within older adult allotment gardeners in
      Wales.
AB  - Previous research has suggested that gardening activity could be an effective
      form of regular exercise for improving physical and psychological health in later
      life. However, there is a lack of data regarding the exercise intensities of
      various gardening tasks across different types of gardening and different
      populations. The purpose of this study was to examine the exercise intensity of
      gardening activity for older adult allotment gardeners in Wales, United Kingdom
      following a similar procedure used in previous studies conducted in the United
      States and South Korea by Park and colleagues (2008a; 2011). Oxygen consumption
      (VO2) and energy expenditure for six gardening tasks were measured via indirect
      calorimetery using the portable Oxycon mobile device. From these measures,
      estimated metabolic equivalent units (METs) were calculated. Consistent with Park
      et al. (2008a; 2011) the six gardening tasks were classified as low to moderate
      high intensity physical activities based on their metabolic values (1.9-5.7
      METs). 

PMID- 24589560
TI  - A prospective phase II trial of fractionated stereotactic intensity modulated
      radiotherapy with or without surgery in the treatment of patients with 1 to 3
      newly diagnosed symptomatic brain metastases.
AB  - BACKGROUND: Several studies have demonstrated that omitting the routine use of
      adjuvant whole-brain radiation therapy for patients with newly diagnosed brain
      metastases may be a reasonable first-line strategy. Retrospective evidence
      suggests that fractionated stereotactic radiotherapy (fSRT) may have a lower
      level of toxicity with equivalent efficacy in comparison with radiosurgery.
      OBJECTIVE: To study the phase II efficacy of using a focally directed treatment
      strategy for symptomatic brain metastases by the use of fSRT with or without
      surgery and omitting the routine use of adjuvant whole-brain radiation therapy.
      METHODS: We used a Fleming single-stage design of 40 patients. Patients were
      eligible if they presented with 1 to 3 newly diagnosed symptomatic brain
      metastases, Karnofsky performance scale (KPS) greater than 60, and histological
      confirmation of primary disease. Patients underwent fSRT with the use of a dose
      of 30 Gy in 5 intensity-modulated fractions as primary or adjuvant treatment
      after surgical resection. The primary end point was the proportion of patients
      who experienced neurological death. Secondary end points were overall survival,
      time to KPS <70, and progression-free survival. RESULTS: Of 40 patients accrued,
      39 were eligible for analysis. The proportion of patients dying of neurological
      causes was 13% (5 patients), which includes 3 patients with an unknown cause of
      death. Median overall survival, time to KPS <70, and progression-free survival
      were 16 (95% confidence interval, 9-23), 14 (95% confidence interval, 7-20), and
      11 (95% confidence interval, 4-21) months, respectively. CONCLUSION: A focally
      directed treatment strategy using fSRT with or without surgery appears to be an
      effective initial strategy. Based on the results of this phase II clinical trial,
      further study is warranted.

PMID- 24589561
TI  - Application of high-definition fiber tractography in the management of
      supratentorial cavernous malformations: a combined qualitative and quantitative
      approach.
AB  - BACKGROUND: High-definition fiber tractography (HDFT), an advanced white matter
      (WM) imaging technique, was evaluated in the management of supratentorial
      cavernous malformations. OBJECTIVE: To investigate the relationship of cavernous
      malformations to the relevant perilesional WM tracts with HDFT and to
      characterize associated changes first qualitatively and then quantitatively with
      our novel imaging measure, quantitative anisotropy (QA). METHODS: Imaging
      analysis was carried out by researchers blinded to the clinical details.
      Contralateral WM tracts were used for comparison. Mean QA values were obtained
      for whole WM tracts. Qualitatively affected superior longitudinal
      fasciculus/arcuate fibers and corticospinal tracts were further analyzed with the
      use of mean QA values for the perilesional segments. RESULTS: Of 10 patients,
      HDFT assisted with the decision-making process and the offer of surgical
      resection in 2 patients, lesion approach and removal in 7 patients, and
      conservative management in 1 patient. Of 17 analyzed WM tracts, HDFT demonstrated
      partial disruption in 2 tracts, complete disruption in 2 tracts, a combination of
      displacement and partial disruption in 1 tract, displacement only in 7 tracts,
      and no change in 5 tracts. Qualitative changes correlated with clinical symptoms.
      Mean QA values for the whole WM tracts were similar, with the exception of 1 case
      demonstrating complete disruption of 2 WM tracts. QA-based perilesional segment
      analysis was consistent with qualitative data in 5 assessed WM tracts.
      CONCLUSION: HDFT illustrated the precise spatial relationship of cavernous
      malformations to multiple WM tracts in a 3-dimensional fashion, optimizing
      surgical planning, and demonstrated associated disruption and/or displacement,
      with both occurring perilesionally. These changes were supported by our
      quantitative marker, which needs further validation.

PMID- 24589562
TI  - Endoscopic treatment of a fourth ventricle arachnoid cyst via the third
      ventricle: a case report.
AB  - BACKGROUND AND IMPORTANCE: Arachnoid cysts within the fourth ventricle have
      rarely been reported in the literature. Different procedures have been performed
      to restore a normal cerebrospinal fluid dynamic or pressure, including shunting
      and partial or complete excision of the cyst by open microsurgery. Cerebrospinal
      fluid shunts give only partial improvement of symptoms and are prone to
      malfunctions. The microsurgical excision of the cyst seems to offer the best
      chance of success. CLINICAL PRESENTATION: We report the case of a fourth
      ventricle arachnoid cyst successfully treated with a complete endoscopic cerebral
      procedure via the third ventricle. CONCLUSION: Endoscopic fenestration of fourth
      ventricle arachnoid cysts may be considered an effective neurosurgical treatment.

PMID- 24589563
TI  - S-adenosylhomocysteine is associated with subclinical atherosclerosis and renal
      function in a cardiovascular low-risk population.
AB  - OBJECTIVE: Although homocysteine has been proposed as a cardiovascular risk
      factor, interventional trials lowering homocysteine have not consistently
      demonstrated clinical benefit. Recent evidence proposed the homocysteine
      metabolite S-adenosylhomocysteine (SAH) rather than homocysteine itself as the
      real culprit in cardiovascular disease. Of note, SAH is predominantly excreted by
      the kidneys, and cannot be lowered by vitamin supplementation. Due to its
      cumbersome measurement, data from large studies on the association between SAH,
      kidney function and cardiovascular disease are not available. METHODS: We
      recruited 420 apparently healthy subjects into our I Like HOMe FU study. Among
      all study participants, we assessed parameters of C1 metabolism (homocysteine,
      SAH and S-adenosylmethionine), renal function (estimated glomerular filtration
      rate [eGFR]) and subclinical atherosclerosis (common carotid intima-media
      thickness [IMT]). eGFR was estimated by the CKD-EPIcreat-cys equation. RESULTS:
      Traditional cardiovascular risk factors and subclinical atherosclerosis were
      associated with SAH, but not with homocysteine (IMT vs SAH: r = 0.129; p = 0.010;
      IMT vs homocysteine: r = 0.009; p = 0.853). Moreover, renal function was more
      closely correlated with SAH than with homocysteine (eGFR vs SAH: r = -0.335; p <
      0.001; eGFR vs homocysteine: r = -0.250; p < 0.001). The association between eGFR
      and SAH remained significant after adjustment for traditional cardiovascular risk
      factors. CONCLUSION: In summary, cardiovascular risk factors, subclinical
      atherosclerosis and eGFR are more strongly associated with SAH than with
      homocysteine in apparently healthy subjects. Thus, SAH might represent a more
      promising target to prevent cardiovascular disease than homocysteine.

PMID- 24589564
TI  - Visceral/epicardial adiposity in nonobese and apparently healthy young adults:
      association with the cardiometabolic profile.
AB  - OBJECTIVE: We investigate associations of regional adipose tissues with
      cardiometabolic profile of nonobese and apparently healthy young adults. METHODS:
      Four hundred twenty-five nonobese and apparently healthy individuals were
      assessed for blood pressure and fasting lipid profile, blood glucose and
      adiponectin. Subcutaneous abdominal adipose tissue (SAT) and ectopic fat depots
      (visceral abdominal adipose tissue [VAT], epicardial adipose tissue [EAT] and
      hepatic fat fraction [HFF]) were quantified by magnetic resonance imaging.
      RESULTS: According to anthropometric measurements, blood pressure and blood
      markers, the population (18-35 years, 54% women) had a low cardiometabolic risk.
      Compared to women, men had more VAT, EAT and HFF, but less SAT. Regional adipose
      tissues were positively correlated with each other. VAT and EAT carried
      significant correlations with all markers of cardiometabolic risk, while SAT and
      HFF correlated variably with these markers. While taking into account age and
      gender, SAT, VAT and EAT were associated with most cardiometabolic markers, while
      HFF was only associated with total cholesterol/high-density lipoprotein ratio
      (TC/HDL-C) and triglycerides (TG). When comparing SAT, VAT and EAT head-to-head,
      VAT was the only adipose tissue location maintaining significant association with
      most markers of cardiometabolic risk. Greater VAT (>=50th percentile) was
      associated with a worse cardiometabolic profile, whether individuals were
      overweight or normal weight. CONCLUSION: Even in nonobese and apparently healthy
      young women and men, accumulation of ectopic visceral adiposity in general, and
      of VAT in particular, is associated with a worse cardiometabolic profile whether
      individuals were overweight or normal weight.

PMID- 24589565
TI  - Type 1 hyperlipoproteinemia due to a novel deletion of exons 3 and 4 in the
      GPIHBP1 gene.
AB  - OBJECTIVES: Type 1 hyperlipoproteinemia is an autosomal recessive disorder
      characterized by severely elevated plasma triglyceride levels, which may lead to
      abdominal pain and pancreatitis, eruptive xanthomas and failure to thrive.
      Mutations in the genes encoding lipoprotein lipase (LPL), apolipoprotein CII
      (APOC2), apolipoprotein AV (APOA5), lipase maturing factor 1 (LMF1) or
      glycosylphosphatidylinositol-anchored high density lipoprotein-binding protein 1
      (GPIHBP1) have been found to cause Type 1 hyperlipoproteinemia. METHODS: Two
      sibpairs belonging to two different branches of an extended pedigree were
      referred for molecular elucidation for their increased plasma triglyceride
      levels, which untreated were >27 mmol/L. The genes LPL, APOC2, APOA5, LMF1 and
      GPIHBP1 were analyzed by DNA sequencing. RESULTS: No mutations were found in LPL,
      APOC2, APOA5 or LMF1. No PCR products were obtained for exons 3 and 4 of GPIHBP1
      from DNA of the 4 affected subjects. Subsequent long-range PCR revealed that the
      four affected were homozygous for a deletion comprising exons 3 and 4 of GPIHBP1.
      No increase in LPL activity was found in post-heparin plasma from the subjects.
      CONCLUSION: Homozygosity for a deletion of exons 3 and 4 of GPIHBP1 results in
      Type 1 hyperlipoproteinemia.

PMID- 24589566
TI  - Effects of a pediatric weight management program with and without active video
      games a randomized trial.
AB  - IMPORTANCE: Active video games may offer an effective strategy to increase
      physical activity in overweight and obese children. However, the specific effects
      of active gaming when delivered within the context of a pediatric weight
      management program are unknown. OBJECTIVE: To evaluate the effects of active
      video gaming on physical activity and weight loss in children participating in an
      evidence-based weight management program delivered in the community. DESIGN,
      SETTING, AND PARTICIPANTS: Group-randomized clinical trial conducted during a 16
      week period in YMCAs and schools located in Massachusetts, Rhode Island, and
      Texas. Seventy-five overweight or obese children (41 girls [55%], 34 whites
      [45%], 20 Hispanics [27%], and 17 blacks [23%]) enrolled in a community-based
      pediatric weight management program. Mean (SD) age of the participants was 10.0
      (1.7) years; body mass index (BMI) z score, 2.15 (0.40); and percentage
      overweight from the median BMI for age and sex, 64.3% (19.9%). INTERVENTIONS: All
      participants received a comprehensive family-based pediatric weight management
      program (JOIN for ME). Participants in the program and active gaming group
      received hardware consisting of a game console and motion capture device and 1
      active game at their second treatment session and a second game in week 9 of the
      program. Participants in the program-only group were given the hardware and 2
      games at the completion of the 16-week program. MAIN OUTCOMES AND MEASURES:
      Objectively measured daily moderate-to-vigorous and vigorous physical activity,
      percentage overweight, and BMI z score. RESULTS: Participants in the program and
      active gaming group exhibited significant increases in moderate-to-vigorous (mean
      [SD], 7.4 [2.7] min/d) and vigorous (2.8 [0.9] min/d) physical activity at week
      16 (P < .05). In the program-only group, a decline or no change was observed in
      the moderate-to-vigorous (mean [SD] net difference, 8.0 [3.8] min/d; P = .04) and
      vigorous (3.1 [1.3] min/d; P = .02) physical activity. Participants in both
      groups exhibited significant reductions in percentage overweight and BMI z scores
      at week 16. However, the program and active gaming group exhibited significantly
      greater reductions in percentage overweight (mean [SD], -10.9%[1.6%] vs 
      5.5%[1.5%]; P = .02) and BMI z score (-0.25 [0.03] vs -0.11 [0.03]; P < .001).
      CONCLUSIONS AND RELEVANCE Incorporating active video gaming into an evidence
      based pediatric weight management program has positive effects on physical
      activity and relative weight. TRIAL REGISTRATION clinicaltrials.gov Identifier:
      NCT01757925.

PMID- 24589567
TI  - A kinetics study on promising hydrogen storage properties of Mg-based thin films
      at room temperature.
AB  - Pd-Mg-Pd thin films with variable thickness of Mg layers were prepared. Their
      optical and electrical changes in both gasochromic and chemochromic processes
      were compared to investigate the kinetics of Mg-based thin films at room
      temperature. Hydrogen absorption and desorption kinetics of Pd-Mg-Pd thin films
      were strongly dependent on the thickness of the Mg layer. Especially, when the
      thickness was lowered to 60 nm, a MgH2 layer formed immediately after exposure to
      H2 at room temperature, while a Mg layer was rapidly generated during hydrogen
      desorption in ambient air. By means of optical and electrical resistance
      measurements, we found that the diffusion process contributed significantly to
      hydrogen absorption and desorption. The remarkable absorption and desorption
      kinetics at room temperature reported here suggested promising applications in Mg
      based energy-efficient devices and hydrogen sensors. 

PMID- 24589568
TI  - Trying to rationalize total synthesis.
AB  - Total synthesis has been held in high esteem for many decades. In recent years,
      however, public opinion has turned more and more skeptical. In particular, long
      and uneventful sequences towards complex yet useless targets are considered a
      waste of resources and are refused funding. There is only one way to remedy this
      unpleasant situation: total synthesis must be efficient and present attractive
      chemistry. This article tries to show some aspects on how this increase in
      efficiency might be achieved.

PMID- 24589569
TI  - Tetrandrine suppresses pro-inflammatory mediators in PMA plus A23187-induced HMC
      1 cells.
AB  - Tetrandrine (TET), a bis-benzylisoquinoline alkaloid from the root of Stephania
      tetrandra, is known to possess antitumor activity in various malignant neoplasms.
      However, the precise mechanism of TET-mediated immune modulation remains to be
      clarified. One of the possible mechanisms for its protective properties is by
      downregulation of the inflammatory responses. In the present study, the human
      mast cell line (HMC-1) was used to investigate this effect. TET significantly
      inhibited the induction of inflammatory cytokines such as tumor necrosis factor
      (TNF)-alpha, interleukin (IL)-6, and IL-8 by phorbol 12-myristate 13-acetate
      (PMA) plus A23187. Moreover, TET attenuated expression of cyclooxygenase (COX)-2.
      In activated HMC-1 cells, the phosphorylation of extra-signal response kinase
      (ERK1/2) and c-jun N-terminal Kinase (JNK1/2), but not p38 mitogen-activated
      protein kinase, was decreased by treatment of the cells with TET. TET inhibited
      PMA plus A23187-induced nuclear factor (NF)-kappaB activation, IkappaB
      degradation and phosphorylation. Furthermore, TET suppressed the expression of
      TNF-alpha, IL-8, IL-6 and COX-2 through suppression of the ERK1/2, JNK1/2,
      IkappaBalpha degradation and phosphorylation, and NF-kappaB activation. These
      results indicated that TET exerted a regulatory effect on inflammatory reactions
      mediated by mast cells.

PMID- 24589570
TI  - Apoptosis induced by islet amyloid polypeptide soluble oligomers is neutralized
      by diabetes-associated specific antibodies.
AB  - Soluble oligomeric assemblies of amyloidal proteins appear to act as major
      pathological agents in several degenerative disorders. Isolation and
      characterization of these oligomers is a pivotal step towards determination of
      their pathological relevance. Here we describe the isolation of Type 2 diabetes
      associated islet amyloid polypeptide soluble cytotoxic oligomers; these oligomers
      induced apoptosis in cultured pancreatic cells, permeated model lipid vesicles
      and interacted with cell membranes following complete internalization. Moreover,
      antibodies which specifically recognized these assemblies, but not monomers or
      amyloid fibrils, were exclusively identified in diabetic patients and were shown
      to neutralize the apoptotic effect induced by these oligomers. Our findings
      support the notion that human IAPP peptide can form highly toxic oligomers. The
      presence of antibodies identified in the serum of diabetic patients confirms the
      pathological relevance of the oligomers. In addition, the newly identified
      structural epitopes may also provide new mechanistic insights and a molecular
      target for future therapy. 

PMID- 24589571
TI  - Effect of vacancy defects on generalized stacking fault energy of fcc metals.
AB  - Molecular dynamics (MD) and density functional theory (DFT) studies were
      performed to investigate the influence of vacancy defects on generalized stacking
      fault (GSF) energy of fcc metals. MEAM and EAM potentials were used for MD
      simulations, and DFT calculations were performed to test the accuracy of
      different common parameter sets for MEAM and EAM potentials in predicting GSF
      with different fractions of vacancy defects. Vacancy defects were placed at the
      stacking fault plane or at nearby atomic layers. The effect of vacancy defects at
      the stacking fault plane and the plane directly underneath of it was dominant
      compared to the effect of vacancies at other adjacent planes. The effects of
      vacancy fraction, the distance between vacancies, and lateral relaxation of atoms
      on the GSF curves with vacancy defects were investigated. A very similar
      variation of normalized SFEs with respect to vacancy fractions were observed for
      Ni and Cu. MEAM potentials qualitatively captured the effect of vacancies on GSF.

PMID- 24589572
TI  - Elevation of ceramide and activation of secretory acid sphingomyelinase in
      patients with acute coronary syndromes.
AB  - BACKGROUND: Although there are several reported evidences for a pathogenic role
      of sphingolipid signaling in atherosclerosis, peripheral blood levels of ceramide
      and secretory acid sphingomyelinase (S-SMase) activity in patients with acute
      coronary syndromes (ACS) have not been evaluated. METHODS AND RESULTS: A total of
      304 CAD patients and 52 healthy individuals were divided into four groups:
      control group (n=52), stable angina pectoris (SAP) group (n=98), unstable angina
      pectoris (UAP) group (n=92), and acute myocardial infarction (AMI) group (n=114).
      Plasma levels of sphingomyelin (SPM) were elevated in patients with UAP and AMI
      compared with those in the control and SAP participants. Plasma ceramide levels
      and S-SMase activity in patients with ACS (including UAP and AMI) on day 0 were
      significantly higher than those in the control and SAP participants. Elevation in
      plasma ceramide levels in patients with UAP and AMI was sustained until a day
      after percutaneous coronary intervention or day 7, respectively. Moreover, in
      patients with UAP, S-SMase activity elevation on day 0 was followed by a gradual
      decrease toward the SAP range up to a day after percutaneous coronary
      intervention. In patients with AMI, elevation in S-SMase activity showed a peak
      on day 3. CONCLUSION: Serial changes in plasma ceramide and S-SMase activity were
      documented in patients with ACS. These findings provide an insight into the
      molecular mechanism of plaque destabilization.

PMID- 24589573
TI  - The efficacy of corneal debridement in the treatment of microsporidial
      keratoconjunctivitis: a prospective randomized clinical trial.
AB  - PURPOSE: To evaluate the efficacy of corneal debridement in the treatment of
      clinically diagnosed cases of microsporidial keratoconjunctivitis. DESIGN:
      Prospective, double-masked randomized clinical trial. METHODS: Patients with
      clinical features such as multifocal, coarse, raised, punctate, round to oval
      epithelial lesions in the cornea in slit-lamp examination with mild to moderate
      conjunctival congestion, suggestive of microsporidial superficial
      keratoconjunctivitis, were included in the prospective study. All patients were
      randomized into 2 groups. Group 1 patients underwent debridement with the help of
      a sterile #15 blade on a Bard-Parker handle, whereas only conjunctival swabs were
      taken from Group 2 patients. All patients were treated with ocular lubricants.
      RESULTS: One hundred and twenty patients with clinical features suggestive of
      microsporidial superficial keratoconjunctivitis were included in the study. The
      mean age was 34.3 +/- 13.6 years (Group 1) and 35.8 +/- 16.2 years (Group 2) (P =
      .59). The mean duration of symptoms was 6.8 +/- 3.9 days (Group 1) and 7.2 +/-
      4.6 days (Group 2) (P = .61). Baseline characteristics showed no difference
      between the 2 groups. The primary outcome was the time from the presentation to
      complete resolution (ie, absence of corneal lesions) of the clinical signs and
      symptoms. The secondary outcomes were final visual acuity and residual corneal
      side effects and/or scarring, if any. The mean resolution time of the corneal
      lesions was 5.7 +/- 4.0 days (Group 1) and 5.9 +/- 3.9 days (Group 2) (P = .83).
      There was no significant difference in final visual outcome in the 2 groups. No
      serious side effects were observed. CONCLUSION: Debridement does not have any
      significant advantage in terms of resolution of the corneal lesions and final
      visual outcome in cases of microsporidial keratoconjunctivitis.

PMID- 24589574
TI  - CTX-M-producing Escherichia coli in Lithuania: associations between sites of
      infection, coresistance, and phylogenetic groups.
AB  - Increasing resistance of Escherichia coli (E. coli) to antibiotics, especially to
      the third-generation cephalosporins, has prompted studies on widespread
      resistance genes such as blaCTX-M and differentiation of E. coli to phylogenetic
      groups. The aim of this study was to determine the associations between the CTX-M
      type and the phylogenetic group, the site of infection, and coresistance in
      Lithuanian E. coli isolates producing beta-lactamases. MATERIAL AND METHODS. A
      total of 90 E. coli ESBL strains were recovered from the lower respiratory tract,
      the urinary tract, sterile body sites, wounds, and other body sites between 2008
      and 2012. The E. coli isolates resistant to at least 2 antibiotics with different
      modes of action along with resistance to cefotaxime were considered as
      multiresistant. The blaCTX-M, blaTEM, blaOXA-1, and blaSHV genes, the
      phylogenetic groups, and the resistance profiles were analyzed. RESULTS. Of the
      90 isolates, 84 (93.3%) were classified as multiresistant and 6 (6.6%) as
      resistant. The blaCTX-M-15 gene was the most prevalent gene followed by the
      blaCTX-M-14 and blaCTX-M-92 genes. The logistic regression analysis revealed the
      associations between CTX-M-15 and resistance to ceftriaxone, between CTX-M-14 and
      resistance to cefoxitin, aztreonam, ampicillin/sulbactam, ticarcillin/clavulanic
      acid, and tobramycin, and between CTX-M-92 and resistance to cefepime,
      piperacillin/tazobactam, gentamicin, and tobramycin. CONCLUSIONS. The results of
      this study showed a significant association between CTX-M-15, CTX-M-14, and CTX-M
      92 beta-lactamases and resistance to some antibiotics as well as CTX-M-14 beta
      lactamase and phylogenetic group A in the Lithuanian population. The associations
      between the CTX-M type and the site of infection were not determined. 

PMID- 24589575
TI  - Associations between the fracture type and functional outcomes after distal
      radial fractures treated with a volar locking plate.
AB  - OBJECTIVE. The aim of this study to investigate the associations of fracture
      type, age, and gender with hand function after distal radius fractures treated
      with a volar locking plate at a 6-month follow-up. MATERIAL AND METHODS. A total
      of 120 patients with displaced distal radius fractures were included into the
      study. They were operated on using a volar locking plate system. All the
      fractures were classified according to the AO classification, and the patients
      were divided into 3 groups by the fracture type. The range of motion and grip
      strength were evaluated at the 6-month follow-up. Multivariate linear regression
      analysis was used to evaluate the associations of age, gender, and fracture type
      with the score of the Disabilities of the Arm, Shoulder and Hand (DASH)
      questionnaire. The DASH questionnaire was completed as an outcome measure.
      RESULTS. A total of 28 patients experienced type A fractures; 70 patients, type B
      fractures; and 22 patients, type C fractures. No statistically significant
      difference regarding age and sex among the groups was observed. At 6 months after
      the surgery, the mean DASH score for type A, B, and C fractures was 16, 13, and
      32, respectively (P=0.01). After the surgery, the radiographic parameters such as
      the volar tilt and the ulnar variance were significantly worse in the patients
      with type C fractures. Grip strength and the range of motion of the contralateral
      healthy hand at the 6-month follow-up were significantly better than those of the
      operated hand. The linear regression analysis showed that the type C fracture was
      the only factor significantly associated with lower DASH score. CONCLUSIONS. The
      patients with type C fractures treated with a volar locking plate had a worse
      wrist function as compared with the patients type A and B fractures at the 6
      month follow-up. The postoperative hand function was significantly associated
      only with the type C fracture, while age and gender had no significant impact. 

PMID- 24589576
TI  - Treatment under dental general anesthesia among children younger than 6 years in
      Lithuania.
AB  - BACKGROUND AND OBJECTIVE: Dental general anesthesia (DGA) is an efficient
      treatment modality for young pediatric dental patients. The aim of this study was
      to identify the reasons for DGA, characteristics of patients receiving treatment
      under DGA, and treatment performed under DGA for children under school age in
      Kaunas, Lithuania. MATERIAL AND METHODS: The study population comprised all
      patients younger than 6 years treated under GA for dental reasons (n=144) at the
      University Hospital during a 3-year period from 2010 to 2012. The data were
      collected by means of clinical dental examinations, a survey of the parents, and
      the patients' dental records and included personal background, reasons for DGA,
      dental status, and treatment provided. RESULTS: More than half (54%) of the
      children were younger than 4 years; 40% of them resided in cities. The dental
      caries experience was high: the mean dmft and d were 12.9 (SD, 3.5) and 12.1 (SD
      3.9), respectively. The majority (81%) of the children had multiple reasons for
      DGA, with the need for excessive treatment (93%), followed by dental fear and
      uncooperativeness (66%), being the most common. The extent of treatment increased
      with age and was greater among patients from rural areas. Of the 1975 primary
      teeth treated under GA, 50% were restored, 32% extracted, and 18% targeted with
      preventive procedures. CONCLUSIONS: Young children with very high levels of
      untreated tooth decay are treated under DGA at the Lithuanian University of
      Health Sciences Hospital. The need for complex treatment as well as dental fear
      and uncooperativeness are the major reasons for DGA. Multiple caries treatments
      and extractions are performed for these patients. This study highlights a great
      need to develop the healthcare system with regard to the appropriate management
      of caries among young children and postoperative DGA care.

PMID- 24589577
TI  - Inhibition of dendritic L-type calcium current by memantine in frog tectum.
AB  - The aim of the study was to explore the effects of memantine on responses
      elicited in the frog tectum by the bursts of spikes of moderate strength of a
      single retina ganglion cell and to gain an insight about the effect of memantine
      on the L-type Ca(2+) current. MATERIAL AND METHODS: The experiments were
      performed in vivo on adult frogs (Rana temporaria). An individual retina ganglion
      cell (or its retinotectal fiber) was stimulated by current pulses delivered
      through a multichannel stimulating electrode positioned on the retina. Responses
      to the discharge of a single retinal ganglion cell were recorded in the tectum by
      an extracellular carbon-fiber microelectrode positioned in the terminal
      arborization of the retinotectal fiber in the tectum layer F. The solution of
      memantine (1-amino-3,5-dimethyladamantane) hydrochloride (30 or 45 MUM) was
      applied onto the surface of the tectum by perfusion at a rate of 0.4 mL/min.
      RESULTS: Memantine (30-45 MUM) largely inhibited the L-type Ca(2+) channel
      mediated slow negative wave and late discharges seen in the tectum responses
      without any effect on fast synaptic retinotectal transmission. CONCLUSIONS: Our
      results suggest that the neuroprotective effect of memantine could arise not only
      through the inhibition of the NMDA receptor current but also through the
      suppression of the L-type Ca(2+) current.

PMID- 24589578
TI  - Factors associated with breastfeeding duration.
AB  - BACKGROUND AND OBJECTIVE: The assessment of the factors associated with
      breastfeeding duration helps in creation of a national policy according to the
      World Health Organization strategy and recommendations. The objective of the
      study was to identify the factors associated with breastfeeding duration.
      MATERIAL AND METHODS: These analyses are based on a sample of mothers with babies
      attending one family health center in Kaunas, Lithuania. Completed questionnaires
      were obtained from 195 mothers (response rate, 97.5%). One year later, the same
      respondents, who had 1-year-old children, answered questions of the second
      questionnaire. RESULTS: Half (53.8%) of the surveyed women breastfed for 3-5
      months, 29.7% for 6 months and more, and 16.5% of the respondents breastfed for
      less than 3 months. The oldest (31-40 years) women breastfed their babies
      significantly longer than the youngest (<20 years) mothers. The mothers with a
      higher education breastfed their babies significantly longer than the less
      educated mothers. The married women breastfed longer than single or living with a
      partner. The mothers who did not give extra fluids and pacifiers breastfed
      significantly longer than the women who gave them. The majority of the mothers
      who had sore nipples, milk stasis, and mastitis breastfed for only up to 3
      months. CONCLUSIONS: Mothers at risk of short breastfeeding duration should be
      targeted as a group for breastfeeding promotion early in the pregnancy. The
      education of healthcare professionals who provide prenatal and postnatal care
      allows them to choose women who need additional breastfeeding support.

PMID- 24589579
TI  - Age-dependent heterogeneity of familiar hypertrophic cardiomyopathy phenotype: a
      role of cardiovascular magnetic resonance.
AB  - In this case report, we present familiar hypertrophic cardiomyopathy with age
      dependent heterogeneity of the disease phenotype among the members of one family
      who carry the same mutation of the myosin-binding protein C gene. Phenotypic
      heterogeneity is common in patients with familial forms of hypertrophic
      cardiomyopathy, both in clinical expression and outcome. Compared with other
      noninvasive cardiac imaging modalities, cardiovascular magnetic resonance
      provides an opportunity to more accurately characterize the varying phenotypic
      presentations of hypertrophic cardiomyopathy. 

PMID- 24589580
TI  - A targeted theranostic platinum(IV) prodrug containing a luminogen with
      aggregation-induced emission (AIE) characteristics for in situ monitoring of drug
      activation.
AB  - A targeted theranostic platinum(IV) prodrug based on a luminogen with aggregation
      induced emission (AIE) characteristics was developed for selective and real-time
      monitoring of drug activation in situ.

PMID- 24589581
TI  - Nonsense-mediated decay as a terminating mechanism for antisense
      oligonucleotides.
AB  - Antisense oligonucleotides (ASOs) are synthetic oligonucleotides that alter
      expression of disease-associated transcripts via Watson-Crick hybridization. ASOs
      that function through RNase H or the RNA-induced silencing complex (RISC) result
      in enzymatic degradation of target RNA. ASOs designed to sterically block access
      of proteins to the RNA modulate mRNA metabolism but do not typically cause
      degradation. Here, we rationally design steric blocking ASOs to promote mRNA
      reduction and characterize the terminating mechanism. Transfection of ASOs
      complementary to constitutive exons in STAT3 and Sod1 results in greater than 70%
      reduction of mRNA and protein. The ASOs promote aberrant exon skipping and
      generation of premature termination codon (PTC)-containing mRNAs. We inhibit the
      nonsense-mediated mRNA decay (NMD) pathway and show that the PTC-containing mRNAs
      are recognized by the UPF1 ATPase, cleaved by the SMG6 endonuclease and degraded
      by the XRN1 cytoplasmic exonuclease. NMD surveillance, however, does not entirely
      explain the mechanism of decreased STAT3 expression. In addition to exon
      skipping, ASO treatment causes intron retention and reduction of chromatin
      associated STAT3 mRNA. The application of steric blocking ASOs to promote RNA
      degradation allows one to explore more nucleotide modifications than tolerated by
      RNase H or RISC-dependent ASOs, with the goal of improving ASO drug properties. 

PMID- 24589583
TI  - MyTaxa: an advanced taxonomic classifier for genomic and metagenomic sequences.
AB  - Determining the taxonomic affiliation of sequences assembled from metagenomes
      remains a major bottleneck that affects research across the fields of
      environmental, clinical and evolutionary microbiology. Here, we introduce MyTaxa,
      a homology-based bioinformatics framework to classify metagenomic and genomic
      sequences with unprecedented accuracy. The distinguishing aspect of MyTaxa is
      that it employs all genes present in an unknown sequence as classifiers,
      weighting each gene based on its (predetermined) classifying power at a given
      taxonomic level and frequency of horizontal gene transfer. MyTaxa also implements
      a novel classification scheme based on the genome-aggregate average amino acid
      identity concept to determine the degree of novelty of sequences representing
      uncharacterized taxa, i.e. whether they represent novel species, genera or phyla.
      Application of MyTaxa on in silico generated (mock) and real metagenomes of
      varied read length (100-2000 bp) revealed that it correctly classified at least
      5% more sequences than any other tool. The analysis also showed that ~10% of the
      assembled sequences from human gut metagenomes represent novel species with no
      sequenced representatives, several of which were highly abundant in situ such as
      members of the Prevotella genus. Thus, MyTaxa can find several important
      applications in microbial identification and diversity studies. 

PMID- 24589582
TI  - A concomitant loss of dormant origins and FANCC exacerbates genome instability by
      impairing DNA replication fork progression.
AB  - Accumulating evidence suggests that dormant DNA replication origins play an
      important role in the recovery of stalled forks. However, their functional
      interactions with other fork recovery mechanisms have not been tested. We
      previously reported intrinsic activation of the Fanconi anemia (FA) pathway in a
      tumor-prone mouse model (Mcm4chaos3) with a 60% loss of dormant origins. To
      understand this further, we introduced a null allele of Fancc (Fancc-), encoding
      a member of the FA core complex, into the Mcm4chaos3 background. Primary
      embryonic fibroblasts double homozygous for Mcm4chaos3 and Fancc-
      (Mcm4chaos3/chaos3;Fancc-/-) showed significantly increased levels of markers of
      stalled/collapsed forks compared to either single homozygote. Interestingly, a
      loss of dormant origins also increased the number of sites in which replication
      was delayed until prophase, regardless of FA pathway activation. These
      replication defects coincided with substantially elevated levels of genome
      instability in Mcm4chaos3/chaos3;Fancc-/- cells, resulting in a high rate of
      perinatal lethality of Mcm4chaos3/chaos3;Fancc-/- mice and the accelerated
      tumorigenesis of surviving mice. Together, these findings uncover a specialized
      role of dormant origins in replication completion while also identifying
      important functional overlaps between dormant origins and the FA pathway in
      maintaining fork progression, genome stability, normal development and tumor
      suppression.

PMID- 24589585
TI  - Heavy metal boryl chemistry: complexes of cadmium, mercury and lead.
AB  - Synthetic routes to the first boryl complexes of cadmium and mercury are reported
      via transmetallation from boryllithium; the syntheses of related group 14 systems
      highlight the additional factors associated with extension to more redox-active
      post-transition elements. 

PMID- 24589584
TI  - Kub5-Hera, the human Rtt103 homolog, plays dual functional roles in transcription
      termination and DNA repair.
AB  - Functions of Kub5-Hera (In Greek Mythology Hera controlled Artemis) (K-H), the
      human homolog of the yeast transcription termination factor Rtt103, remain
      undefined. Here, we show that K-H has functions in both transcription termination
      and DNA double-strand break (DSB) repair. K-H forms distinct protein complexes
      with factors that repair DSBs (e.g. Ku70, Ku86, Artemis) and terminate
      transcription (e.g. RNA polymerase II). K-H loss resulted in increased basal R
      loop levels, DSBs, activated DNA-damage responses and enhanced genomic
      instability. Significantly lowered Artemis protein levels were detected in K-H
      knockdown cells, which were restored with specific K-H cDNA re-expression. K-H
      deficient cells were hypersensitive to cytotoxic agents that induce DSBs, unable
      to reseal complex DSB ends, and showed significantly delayed gamma-H2AX and 53BP1
      repair-related foci regression. Artemis re-expression in K-H-deficient cells
      restored DNA-repair function and resistance to DSB-inducing agents. However, R
      loops persisted consistent with dual roles of K-H in transcription termination
      and DSB repair. 

PMID- 24589586
TI  - Plasma cell-free DNA for predicting outcomes of patients with HBV-related acute
      on-chronic liver failure: a pilot study.
AB  - OBJECTIVE: Cell-free DNA (cfDNA) was shown to be a prognostic marker for diverse
      pathological states in the Intense Care Unit, but little is known of the role of
      cfDNA in HBV-related acute-on-chronic liver failure (ACLF). We hypothesize that
      cfDNA can also be a promising prognostic as well as a diagnostic marker in
      patients with HBV-related ACLF. METHODS: Thirty-eight patients with HBV-related
      ACLF admitted in the Intense Care Unit were enrolled in the study. The patients
      were divided, according to the improvement of liver function at discharge, into
      favorable prognosis group (group 1, n=17) and poor prognosis group (group 2,
      n=19). Plasma samples were collected from each patient at hospitalization and at
      discharge to measure cfDNA by real-time quantitative PCR. MELD score was
      calculated at the same time points. RESULTS: The average level of cfDNA of group
      1 was lower than that of group 2 both at the time of hospitalization (P=0.044)
      and at discharge (P<0.001). There was no difference in MELD score between the two
      groups at hospitalization. Significant correlations were found of cfDNA levels
      with the MELD score, TBIL, CRE and INR both at hospitalization (gamma=0.662,
      P<0.001; gamma=0.356, P=0.033; gamma=0.360, P=0.031; gamma=0.570, P<0.001,
      respectively) and at discharge (gamma=0.854, P<0.001; gamma=0.821, P<0.001;
      gamma=0.650, P<0.001; gamma=0.638, P<0.001, respectively). The ROC curve showed
      that cfDNA level at discharge was optimal in diagnosing ACLF with an area under
      curve (AUC) value of 0.96, followed by deltacfDNA (AUC value of 0.923) and cfDNA
      level at hospitalization (AUC value of 0.667). The MELD scores had an AUC value
      of only 0.545 at the time of hospitalization. CONCLUSION: cfDNA may serve as a
      promising prognostic and diagnostic marker for predicting in-hospital prognosis
      of HBV-related ACLF within 2 to 8 weeks.

PMID- 24589587
TI  - [CXCR4 and Nrf2 expressions in non-small cell lung cancer and their clinical
      implications].
AB  - OBJECTIVE: To detect the expressions of CXCR4 and Nrf2 in non-small cell lung
      cancer (NSCLC) tissues and analyze their association with the clinicopathological
      features of NSCLC. METHODS: We investigated the expressions of CXCR4 and Nrf2 in
      66 NSCLC and corresponding distant normal tissue specimens using
      immunohistochemistry and real-time PCR. RESULTS: The expressions of CXCR4 protein
      and mRNA were significantly higher in NSCLC tissue specimens than in the distant
      normal tissues, while the expression of Nrf2 protein and mRNA increased
      significantly in NSCLC tissues compared to those in the distant normal tissues
      (P<0.01). A high expression level of CXCR4 was positively correlated with a large
      tumor size (P=0.048), poor differentiation (P=0.024), advanced TNM stage
      (P=0.018), lymph node metastasis (P=0.004), and distant metastasis (P=0.016). The
      expression of Nrf2 protein was positively correlated with a large tumor size
      (P=0.008), advanced TNM stage (P=0.028), lymph node metastasis (P=0.038), and
      distant metastasis (P=0.023). A strong correlation was found between CXCR4 and
      Nrf2 expressions in NSCLC tissues (r=0.324, P<0.01), and the co-expression of
      CXCR4 and Nrf2 was strongly correlated with lymph node metastasis and distant
      metastasis. CONCLUSION: Abnormal expressions of CXCR4 and Nrf2 may contribute to
      the progression and malignant biological behavior of NSCLC.

PMID- 24589588
TI  - [Effects of metformin on human oral cancer KB cell proliferation and apoptosis in
      vitro].
AB  - OBJECTIVE: To investigate the effects of metformin on the proliferation and
      apoptosis of human oral cancer cell line KB in vitro. METHODS: Human oral cancer
      cell line KB was exposed to different doses of metformin (0, 1.25, 2.5, 5, 10,
      and 20 mmol/L), and the changes in cell viability were detected using MTT assay.
      Colony formation of the cells was observed following an 8-day metformin exposure.
      The changes in mitochondrial membrane potential were measured by JC-1 assay, and
      PI staining was used to observe the cell apoptosis. Western blotting was employed
      to detect the changes in the protein expressions of GRP78 and activated caspase
      3. RESULTS: Metformin exposure caused time- and dose-dependent suppression of KB
      cell proliferation, and exposure to 5 mmol/L metformin for 24, 48 and 72 h
      resulted in cell survival rates of 68.0%, 36.9%, and 14.5%, respectively.
      Metformin significantly inhibited KB cell colony formation. Exposure of the cells
      to increased concentrations of metformin gradually increased the apoptotic rate
      and decreased mitochondrial membrane potential. Metformin caused an initial up
      regulation followed by a down-regulation of GRP78 expression in KB cells and
      increased the expression of activated caspase-3. CONCLUSION: Metformin can
      inhibit the proliferation and induce apoptosis of KB cells, the mechanism of
      which may involve the activation of the mitochondrial apoptotic pathway and
      endoplasmic reticulum stress.

PMID- 24589589
TI  - [miR-520a regulates ErbB4 expression and suppresses proliferation and invasion of
      esophageal squamous cell carcinoma].
AB  - OBJECTIVE: To investigate the role of miR-520a in regulation ErbB4 expression and
      the biological behavior of esophageal squamous cell carcinoma (ESCC). METHODS:
      The role of miR-520a in regulating the expression of ErbB4 was investigated by
      Western blotting and luciferase reporter assay system. The effect of miR-520a on
      the proliferation and invasion of ESCC cells was detected by MTT and Transwell
      invasion assay, respectively. RESULTS: Western blotting and luciferase reporter
      assay revealed that miR-520a down-regulated the expression of ErbB4 in vitro. miR
      520a significantly inhibited the proliferation and suppressed the invasion of
      ESCC cell line Eca109. CONCLUSION: miR-520a regulates the expression of ErbB4 and
      suppresses the proliferation and invasion of ESCC cells in vitro, suggesting its
      role as a tumor suppressor.

PMID- 24589590
TI  - [A novel histological typing and grading-scale system of colorectal cancer].
AB  - OBJECTIVE: To formulate a novel histological typing and grading-rated system for
      colorectal cancer (CRC) for evaluating the biological behavior of CRC and
      prognosis. METHODS: According to the highly heterogeneous histological features,
      WHO classification and histological differentiation criteria, and other
      biological behavior parameters of CRC, a novel histological typing and grading
      scale system for CRC was designed. The histological typing and corresponding
      grading-scale of CRC was defined as the following: (1) No mucin-producing
      adenocarcinoma, including tubular adenocarcinoma, sieve-like acne adenocarcinoma,
      medullary carcinoma, serrated adenocarcinoma and micropapillary carcinoma, etc.
      (1-3 points); (2) Mucin-producing adenocarcinoma, including mucinous
      adenocarcinoma and signet ring cell carcinoma (3-4 points); (3) Squamous cell
      carcinoma (1-3 points); (4) Neuroendocrine tumors, including neuroendocrine
      tumors, neuroendocrine carcinoma (1-4 points); (5) The special type of CRC,
      including clear cell carcinoma, spindle cell carcinoma, etc. (4-points); (6)
      Undifferentiated carcinoma (5 points). The pathology report form was formatted
      based on the major histological type with the secondary histological type. The
      final total score of CRC was defined as the sum of the corresponding grading
      scores for different histological types. The total score of a single-structure
      CRC was defined as the corresponding grading score multiplied by 2. A total of
      666 patients with advanced CRC were pathologically reviewed and analyzed to
      assess the correlation of the histological typing and grading scores with TNM
      staging and lymph node metastasis. RESULTS: The results showed a significant
      correlation of the histological grading-scale and TNM staging and lymph node
      metastasis (P<0.05). The scores of CRC histological grading-scale increased
      synchronously with the TNM staging and lymph node metastasis rate. CONCLUSION:
      The novel histological grading system allows objective evaluation of the
      biological behaviors and prognosis of CRC for determining individualized
      postoperative treatment. This system still needs further revision and updates
      based on evidence from prospective, multi-centered, large-scale trials.

PMID- 24589591
TI  - [Pathogenesis of uropathogenic Escherichia coli: role of outer membrane protein T
      and the mechanism].
AB  - OBJECTIVE: To study the role of outer membrane protein T (OmpT) in the
      pathogenesis of uropathogenic Escherichia.coli. METHODS: In cultured human
      bladder epithelial cell line 5637, we examined the adhesion ability of wild-type
      (CFT073), ompT gene knockout (COTD), and revertant (pST) strains of E.coli to the
      cells and the extracellular matrix (ECM). The expressions of the adhesion gene
      iha and virulence gene iroN were detected by real-time PCR. Murine models of
      urinary tract infection with the 3 strains were established to evaluate the
      bacterial burden of the bladder and kidney tissue and bacterial counts in blood.
      We also detected the expressions of interleukin-6 (IL-6) and IL-8 in the bladder
      and kidney tissues of the mice. RESULT: The COTD strain showed a significantly
      lower cell adhesion rate than CFT073 strain [(4.62?0.39)% vs (8.81?1.13)%,
      P<0.05] with also a lower ECM-adhesion rate [(4.95?0.59)% vs (8.85?0.79)%,
      P<0.05]. The mRNA expressions of iha and iroN in CFT073 strain were 2.1 and 3.8
      times that of COTD strain. In the mouse model, the mean bacterial load of CFT073
      strain in the bladder tissue was 6.36?0.06, significantly greater than that of
      COTD (6.01?0.07) and revertant (6.29?0.06) strains (P<0.05); the bacterial load
      of CFT073 strain in the kidney tissue was also significantly higher than that of
      COTD strain (6.25?0.05 vs 5.87?0.06, P<0.05). In mice infected with the wild
      type, knockout, and revertant strains, the detection rates of IL-6, which were
      identical to those of IL-8, in the inflammatory bladder and kidney tissues were
      60%, 12.5%, and 50%, respectively. CONCLUSIONS: OmpT may regulate the expression
      of the adhesion gene iha and the transferrin gene iroN to affect the adhesion of
      uropathogenic E.coli to host cells.

PMID- 24589592
TI  - [Infection with L-form of Helicobacter pylori and expressions of MIF, MMP9 and
      VEGF in gastric carcinoma].
AB  - OBJECTIVE: To investigate the correlation between infection with L-form of
      Helicobacter pylori (Hp-L) and the expressions of macrophage migration inhibition
      factor (MIF), matrix metalloproteinase 9 (MMP9), and vascular endothelial growth
      factor (VEGF) in gastric cancer. METHODS: Hp-L was examined in 80 gastric
      carcinoma and 50 adjacent normal tissues by Gram staining and immunohistochemical
      staining, and the expressions of MIF, MMP9 and VEGF were detected by
      immunohistochemical staining; the expression of MIF mRNA was detected by RT-PCR
      and the expression of MIF, MMP9 and VEGF proteins were detected by Western
      blotting in 30 fresh gastric cancer tissues and the corresponding adjacent
      tissues. RESULTS: Of the 80 gastric carcinoma tissues, 57 (71.25%) showed Hp-L
      positivity detected by both Gram staining and immunohistochemical staining, as
      compared with a rate of only 14% in the adjacent normal tissues (P<0.05). The
      gastric carcinoma tissues showed higher expression levels of MIF, MMP9 and VEGF
      proteins than the corresponding adjacent normal mucosa; the positivity MIF, MMP-9
      and VEGF proteins were significantly higher in Hp-L-positive gastric carcinoma
      than in Hp-L-negative cases (P<0.05). Positive correlations were found between Hp
      L positivity and the expressions of MIF, MMP-9 and VEGF (r=0.598, 0.292, 0.341,
      respectively, P<0.05). The 30 fresh gastric cancer tissues showed also
      significantly higher MIF mRNA expression and MIF, MMP-9 and VEGF protein
      expressions than the adjacent tissues (t=3.729, P<0.01). The expressions of MIF
      and MMP-9 were also related to the clinicopathological factors including lymph
      node metastasis and depth of invasion (P<0.05). CONCLUSION: Infection with L-form
      of Hp-L can be an important factor that contributes to the invasion and
      metastasis of gastric carcinoma, the mechanism of which involves up-regulated
      expressions of MIF, MMP-9 and VEGF.

PMID- 24589593
TI  - [Ca(2+)-activated K(+) channel switching in smooth muscle participates in
      atherosclerosis development in diabetic rats].
AB  - OBJECTIVE: To investigate the changes in aorta morphology and Ca(2+)-activated
      K(+) (KCa) channel expression in the diabetic rats. METHODS: A diabetic rat model
      was established by a single intraperitoneal injection of streptozotocin (30
      mg/kg) after a modified high fat and glucose diet for 8 weeks. Pathological
      changes in the aorta were observed with HE staining, elastic fiber staining,
      Masson's trichrome staining and immunohistochemistry. Both the mRNA and protein
      levels of KCa channels in the aorta were measured by RT-PCR and Western blotting.
      RESULTS: Early atherosclerotic changes were observed in the aorta wall of the
      diabetic rats. The mRNA and protein levels of KCa1.1 channel alpha- and beta
      subunits were significantly decreased, while the expression of KCa3.1 channels
      was obviously enhanced in the middle layer of the aorta in the diabetic rats.
      CONCLUSION: KCa channel switching in smooth muscles may play a role in the
      development of atherosclerosis in diabetic rats.

PMID- 24589594
TI  - [2-Deoxy-D-glucose combined with Taxol inhibits VEGF expression and induces
      apoptosis in orthotopically transplanted breast cancer in C3H mice].
AB  - OBJECTIVE: To investigate the antineoplastic effects of 2-Deoxy-D-glucose (2-DG)
      combined with Taxol on orthotopically transplanted breast cancer in C3H mice and
      explore the mechanism. METHODS: C3H mice bearing orthotopically transplanted
      breast cancer xenograft were randomly divided into 4 groups, namely the control
      group, 2-DG group, Taxol group, and 2-DG+Taxol group. The corresponding drugs
      were administered intraperitoneally every 3 days for 18 consecutive days, and the
      tumor volume was measured every 3 days to draw the tumor growth curve. The mice
      were then sacrificed to measure the tumor weight on day 19 and examine tumor cell
      apoptosis with TUNEL assay and VEGF expression using immunohistochemistry.
      RESULTS: 2-DG combined with Taxol obviously suppressed the tumor growth with a
      tumor inhibition rate of 66.06% as compared to the rate of 36.97% in Taxol group.
      The combined treatment also caused more obvious cell apoptosis and significantly
      reduced VEGF expression in the tumor cells as compared with the other groups.
      CONCLUSION: 2-DG can enhance the inhibitory effect of Taxol on orthotopically
      transplanted breast cancer xenograft in C3H mice probably by inducing tumor cell
      apoptosis and lowering VEGF expressions.

PMID- 24589595
TI  - [Effects of pioglitazone on myocardial peroxisome proliferator-activated receptor
      gamma co-activator lalpha expression in rats with myocardial ischemia/reperfusion
      injury].
AB  - OBJECTIVE: To investigate the effects of pioglitazone on the expression of
      peroxisome proliferator-activated receptor gamma co-activator lalpha (PGC-lalpha)
      in rat myocardium following myocardial ischemia/reperfusion (I/R) injury.
      METHODS: Twenty-four SD rats were randomly divided into 4 equal groups, namely
      I/R group, pioglitazone (5 mg/kg daily) group, pioglitazone (10 mg/kg daily)
      group, and pioglitazone (10 mg/kg) +peroxisome proliferator-activated receptor
      gamma (PPARgamma)-specific antagonist GW9662 group. Myocardial I/R injury was
      induced by ligation of the left anterior descending coronary artery for 30 min
      and reperfusion for 120 min. Myocardial apoptosis following I/R injury was
      examined with TUNEL assay; RT-PCR and Western blotting were employed to detect
      the expression of PGC-lalpha mRNA and protein, respectively. RESULTS:
      Pioglitazone treatment significantly suppressed myocardial apoptosis
      (21.4%?8.8%,17.3%?8.7%, 40.1%?12.3%, P<0.05) following I/R injury and up
      regulated myocardial PGC-lalpha expression at both the mRNA and protein levels
      (P<0.05), but these effects were antagonized by GW9662 (P<0.05). CONCLUSION:
      Pioglitazone can inhibit myocardial apoptosis induced by I/R injury and up
      regulate myocardial PGC-lalpha expression, and these effects are mediated by
      PPARgamma.

PMID- 24589596
TI  - [Effect of endotoxin pretreatment-induced glycogen synthase kinase-3 inhibition
      on glycogen metabolism in rat liver and the mechanism].
AB  - OBJECTIVE: To investigate the changes in the functional activity of glycogen
      synthase kinase-3 (GSK-3) in the hepatic tissue after endotoxin
      (lipopolysaccharide, LPS) tolerance and explore the effects of LPS-induced GSK-3
      inhibition on glycogen metabolism in the liver. METHODS: Male SD rats were
      randomly divided into normal control, endotoxin pretreatment and GSK-3 inhibitor
      (lithium chloride) groups with corresponding pretreatments prior to a large dose
      of LPS challenge (10 mg/kg) to induce liver injury. Glycogen deposition and
      content in the hepatic tissue was detected using periodic acid-Schiff (PAS)
      staining and a glycogen quantification kit, respectively. Western blotting was
      performed for semi-quantitative analysis of protein level and inhibitory
      phosphorylation of GSK-3, and a Coomassie brilliant blue G-250-based colorimetric
      assay was used to detect calpain activity in the liver. RESULTS: Glycogen content
      in the liver decreased significantly after LPS challenge in all the 3 groups
      (P<0.05) but showed no significant difference among the groups (P>0.05). Both LPS
      and lithium chloride pretreatments caused a significant increase of liver
      glycogen content (P<0.05). LPS pretreatment induced inhibitory phosphorylation of
      GSK-3beta (P<0.05) and partial cleavage of GSK-3alpha but did not affect the
      expression of GSK-3 protein (P>0.05). Large-dose LPS challenge significantly
      increased the activity of calpain in the liver tissue (P<0.05) to a comparable
      level in the 3 groups (P>0.05). CONCLUSION: Endotoxin pretreatment induces
      inhibitory phosphorylation of GSK-3beta and partial cleavage of GSK-3alpha and
      promotes the deposition of liver glycogen but does not affect the activity of
      calpain, which may contribute to an increased glycogen reserve for energy supply
      in the event of large-dose LPS challenge.

PMID- 24589597
TI  - [Assessment of plantar fasciitis using shear wave elastography].
AB  - OBJECTIVE: To assess the stiffness and thickness of the plantar fascia using
      shear wave elastography (SWE) in healthy volunteers of different ages and in
      patients with plantar fasciitis. METHODS: The bilateral feet of 30 healthy
      volunteers and 23 patients with plantar fasciitis were examined with SWE. The
      plantar fascia thickness and elasticity modulus value were measured at the
      insertion of the calcaneus and at 1 cm from the insertion. RESULTS: The elderly
      volunteers had a significantly greater plantar fascia thickness measured using
      conventional ultrasound (P=0.005) and a significantly lower elasticity modulus
      value than the young volunteers (P=0.000). The patients with fasciitis had a
      significantly greater plantar fascia thickness (P=0.001) and a lower elasticity
      modulus value than the elderly volunteers (P=0.000). The elasticity modulus value
      was significantly lower at the calcaneus insertion than at 1 cm from the
      insertion in patients with fasciitis (P=0.000) but showed no significantly
      difference between the two points in the elderly or young volunteers (P=0.172,
      P=0.126). CONCLUSION: SWE allows quantitative assessment of the stiffness of the
      plantar fascia, which decreases with aging and in patients with plantar
      fasciitis.

PMID- 24589598
TI  - [Correlation analysis between miR-124 rs531564 polymorphisms and susceptibility
      to cervical cancer].
AB  - OBJECTIVE: To investigate the correlation between miR-124 rs531564 polymorphisms
      and the susceptibility to cervical cancer in Chinese Han women in Guangdong
      Province. METHODS: The genotypes of miR-124 rs531564 polymorphism were determined
      using polymerase chain reaction-based ligase detection reaction (PCR-LDR) in 107
      cervical cancer patients and 208 healthy female blood donors. The correlation
      between the polymorphism and the susceptibility to cervical cancer was evaluated
      using unconditional logistic regression analysis. RESULTS: The incidence of HPV
      infection in the patients (93.1%) was much higher than that in the control
      subjects (16.8%, P<0.001), suggesting the importance of HPV infection as a
      critical risk factor for cervical cancer. The G allele of miR-124 rs531564
      polymorphism in the cervical cancer patients was much less frequent than that in
      the controls (8.0% vs 15.1%, P=0.014), suggesting its possible role as a
      protective allele. Compared with those carrying CC genotype, individuals carrying
      the CG and GG genotypes showed a significantly reduced risk for cervical cancer
      (OR=0.47, 95% CI=0.26-0.88, P=0.017), and this protective role of the G allele
      was more prominent in older women (>=45 years old) (OR=0.28, 95% CI=0.10-0.76,
      P=0.012). CONCLUSION: miR-124 rs531564 polymorphism may play a role in cervical
      cancer susceptibility in Chinese Han women, and G allele is associated with a
      reduced risk of cervical cancer.

PMID- 24589599
TI  - [Lipopolysaccharide sensitizes neonatal mice to hyperoxia-induced immature brain
      injury].
AB  - OBJECTIVE: To explore the effect of low-concentration lipopolysaccharide (LPS)
      pretreatment on hyperoxia-induced immature brain injury in neonatal mice and
      explore and the related mechanisms. METHODS: Forty-eight neonatal mice on
      postnatal day 3 (PND3) were randomized into normal control group, LPS (0.3 mg/kg)
      group, hyperoxia group (hyperoxia exposure for 24 h), and hyperoxia+LPS group
      (hyperoxia exposure for 24 h 30 min after 0.3 mg/kg LPS treatment). At PND5, all
      the neonatal mice were sacrificed to examine the morphological changes of
      microglia in the periventricular white matter using Tomato lectin staining,
      measure malondialdehyde (MDA) content in the immature brain, detect mRNA
      expression of tumor necrosis factor-alpha (TNF-alpha) using real-time PCR, and
      determine caspase-3 protein expression with Western blotting. RESULTS: Compared
      with the control group, exposures to LPS, hyperoxia, and both all resulted in
      microglia activation in the periventricular white matter. The number of activated
      microglia, MDA content, TNF-alpha mRNA expression and caspase-3 protein
      expression in the immature brain were significantly higher in hyperoxia group
      than in the control group and LPS group (P<0.05). LPS pretreatment significantly
      enhanced hyperoxia-induced microglia activation in the immature brain (P<0.05).
      CONCLUSION: Hyperoxia causes immature brain injury mediated by microglia
      activation, and LPS pretreatment can enhance such brain injury in neonatal mice.

PMID- 24589600
TI  - [miR-221 mediates epithelial-mesenchymal transition-related gene expressions via
      regulation of PTEN/Akt signaling in drug-resistant glioma cells].
AB  - OBJECTIVE: To investigate the correlation between miR-221 and epithelial
      mesenchymal transition (EMT) in drug-resistant glioma cells. METHODS: The
      expression levels of miR-221, PTEN, p-Akt, E-cadherin, vimentin, and MRP1 were
      quantitatively analyzed in Z1 cells (primary drug-resistant cells), Z2 cells
      (drug-sensitive cells) and Z2-BCNU cells (drug-resistant cells) using fluorescent
      real-time PCR and Western blotting. RESULTS: The expression levels of PTEN were
      significantly increased in Z2 cells compared with Z1 and Z2-BCNU cells which
      overexpressed miR-221 and vimentin. The expression levels of vimentin, p-Akt and
      MRP1 were significantly decreased in Z2 cells overexpressing E-cadherin.
      CONCLUSION: MiR-221 regulates the expression of EMT-related genes through down
      regulation of PTEN and activation of PI3-K/Akt signaling.

PMID- 24589601
TI  - [Feasibility of continuous extracorporeal normothermic liver perfusion using
      autologous blood: a study in pigs].
AB  - OBJECTIVE: To study the feasibility of sustaining the viable status of a liver
      graft in at least 96 h by extracorporeal perfusion using autologous blood.
      METHODS: Eight extracorporeal porcine liver perfusions using autologous blood
      were performed, each for 96 h with hepatectomy, cold preservation, cannulation of
      vessels, and initiation of perfusion with normothermic oxygenated porcine blood.
      The graft viability was assessed by metabolic, synthetic, hemodynamic, and
      histologic parameters. RESULTS: After 96 h of normothermic, extracorporeal
      perfusion using autologous blood, the isolated livers maintained normal
      physiological levels of pH and electrolytes with sustained hepatic protein
      synthesis (complement and factor V) throughout the perfusion. Hemodynamic
      parameters maintained normal physiological ranges. Histological inspection
      demonstrated good preservation of the liver with a good architectural integrity.
      CONCLUSION: It is possible to sustain the viable status of a liver graft within
      96 h by extracorporeal perfusion using autologous blood.

PMID- 24589602
TI  - [Genome-wide screening of CpG island methylation changes induced by low-dose X
      ray radiation in mice].
AB  - OBJECTIVE: To study the methylation changes in promoter CpG islands induced by
      low-dose X-ray radiation (LDR). METHODS: Twenty male BALB/c mice were randomly
      divided into control and fractionated radiation group exposed to 6 MV X-ray for
      10 days (0.05 Gy/day). All the mice were sacrificed 2 h after the last radiation
      on day 10, and blood samples were collected for detecting DNA methylation changes
      using Roche-NimbleGen mouse DNA methylation 3*720K Promoter Plus CpG Island
      Array. MeDIP-qPCR was used to further validate the methylation status of specific
      genes. RESULTS: A total of 811 genes were found to show specific hypermethylation
      in fractional radiation group as compared with the control group, involving
      almost all the main biological processes by GO analysis. Eight candidate genes
      (Rad23b, Tdg, Ccnd1, Ddit3, Llgl1, Rasl11a, Tbx2, and Slc6a15) were confirmed to
      be hypermethylated in LDR samples by MeDIP-qPCR, consistent with the results of
      the methylation chip study. CONCLUSION: LDR induces promoter hypermethylation on
      specific genes, which may contribute to radiation-induced pathogenesis.

PMID- 24589603
TI  - [Effects of estrogen on renal function of pregnant rabbits with hemorrhagic
      shock].
AB  - OBJECTIVE: To evaluate the effects of estrogen on renal function of pregnant
      rabbits with hemorrhagic shock. METHODS: Forty pregnant New Zealand white rabbits
      were randomized into 4 groups, namely normal control group (NG group, with
      anesthesia only), estrogen group (E2 group, with additional estrogen injection at
      60 min), estrogen-hemorrhagic shock (E2SG) group and fructose-hemorrhagic shock
      (FSG) group. In the latter two groups, the rabbits were subjected to phlebotomy
      for 15 min to induce hemorrhagic shock with a blood pressure of 40 mmHg; after
      maintenance of the pressure for 45 min, intravenous injections of estrogen or
      fructose were given before resuscitation 20 min later. Blood urea nitrogen (BUN)
      and creatinine (Cr) concentration were measured at different time points and
      renal pathology of the rabbits was observed. RESULTS: No significant differences
      were founding serum BUN and Cr levels between NG and E2G groups during the
      experiment. In FSG and E2SG groups, serum BUN level began to increase at 80 min
      after hemorrhagic shock and was significantly higher in FSG group (P<0.05); serum
      Cr level increased progressively from the start of the experiment and began to
      decrease at 60 min, with a faster rate of reduction in E2SG group (P<0.05).
      CONCLUSION: Estrogen can effectively lower serum BUN and Cr levels and ameliorate
      renal pathologies to offer protective effect in pregnant rabbits against
      hemorrhagic shock.

PMID- 24589604
TI  - [Effect of Smilax china bioactive fraction on tumor necrosis factor-alpha and
      interleukin-4 contents in uterine tissue of rats with chronic pelvic inflammatory
      disease].
AB  - OBJECTIVE: To study the mechanism that mediates the therapeutic effect of the
      bioactive fraction of Baqia (Smilax china) on chronic pelvic inflammatory disease
      (CPID). METHODS: Seventy rats were randomized into CPID model group, sham
      operated group, normal control group, Jingangteng capsule group, and high-,
      medium-, and low-dose Baqia groups. Rat models of CPID were established by
      inducing chemical burns of the uterus and corresponding treatments were
      administered. After 14 days of treatment, the rat uterus was observed for
      swelling and inhibition rate, and the expressions of tumor necrosis factor-alpha
      (TNF-alpha) and interleukin-4 (IL-4) in the uterine tissues were determined using
      enzyme-linked immunosorbent assay. RESULTS: The bioactive fraction of Baqia at
      the 3 doses obviously reduced the inflammatory cells in the endometrium, promoted
      epithelial cell proliferation, and ameliorated congestion and edema of the
      serosa. High and medium doses of Baqia bioactive fraction significantly decreased
      uterus swelling rate of the rats (P<0.01). All the 3 doses of the Baqia bioactive
      fraction obviously decreased uterine TNF-alpha content (P<0.01) and significantly
      increased uterine IL-4 expression level (P<0.05), and IL-4 up-regulation was
      especially obvious in high and medium dose groups (P<0.01). CONCLUSION: Baqia
      bioactive fraction can ameliorate uterine swelling, lower uterine TNF-alpha and
      increase IL-4 expressions in rats with CPID, which may be a pharmacological
      mechanism underlying its therapeutic effect on CPID and cervical adhesion.

PMID- 24589605
TI  - [GM6001 suppresses scar formation after glaucoma filtration surgery in rabbits].
AB  - OBJECTIVE: To study the effect of matrix metalloproteinases inhibitor GM6001 in
      suppressing scar tissue formation in the filtering passage after glaucoma
      filtration surgery. METHODS: Twenty-four pigmented rabbits (48 eyes) underwent
      trabeculectomy followed by subconjunctival injection of GM6001 in the right eye
      (treated eyes) and injection of PBS in the left eye (control) once a day. The
      intraocular pressure was monitored postoperatively and proliferating cell nuclear
      antigen (PCNA)- and alpha-smooth muscle actin (alpha-SMA)-positive cells in the
      filtering pathway were detected using immunohistochemistry. RESULTS: On
      postoperative days 7, 14, 21, and 28, the intraocular pressure was significantly
      lower in the treated eyes (GM6001) than in the control eyes (P<0.01). The counts
      of PCNA- and alpha-SMA-positive cells were also significantly lowered in the
      treated than in the control eyes (P<0.01). CONCLUSION: GM6001 can inhibit
      excessive proliferation of the fibroblasts in the filtering pathway to suppress
      scar tissue formation and prolong the existence of the functional filtration bleb
      in rabbits.

PMID- 24589606
TI  - [Effect of siRNA targeting HDAC1 gene on proliferation, apoptosis, histone
      acetylation, and histone methylation in gastric cancer cells in vitro].
AB  - OBJECTIVE: To investigate the effect of silencing histone deacetylases 1 (HDAC1)
      gene by RNA interference on the proliferation, apoptosis and histone modulation
      in gastric cancer MGC-803 cell line. METHODS: The optimal segment targeting HDAC1
      gene was designed and transfected into MGC-803 cells by Lipofectamine TM2000.
      HDAC1 mRNA and protein in the transfected cells were detected by RT-PCR and
      Western blotting, respectively. The growth inhibition of MGC803 cells was
      evaluated by MTT assay and the cell apoptosis was detected with TUNEL assay. The
      expression of Bcl-2, procaspase-9, procaspase-3, c-Myc, histone acetylation of
      H3, H4, and histone methylation of H3K9 was detected by Western blotting.
      RESULTS: The siRNA targeting HDAC1HDAC1 markedly suppressed mRNA expression,
      inhibited cell proliferation and induced apoptosis of MGC-803 cells in a
      concentration manner. Transfection of the cells with HDAC1 siRNA at 0, 30, 60,
      and 120 nmol/L for 24 h resulted in a cell apoptotic rate of (4.8?2.7)%,
      (18.5?3.5)%, (41.4?4.3)%, and (59.2?5.5)%, respectively, and caused down
      regulation of the expressions of Bcl-2, proCaspase9, proCaspase3 and c-Myc,
      upregulation of histone acetylation of H3, H4, and down-regulation of histone
      methylation of H3K9. CONCLUSION: Silencing HDAC1 gene expression with HDAC1 siRNA
      can promote histone H3 and H4 acetylation and inhibit histone methylation of H3K9
      to suppress the proliferation and induce apoptosis of gastric cancer MGC-803
      cells.

PMID- 24589607
TI  - [Effects of stable ANO1 overexpression on biological behaviors of human laryngeal
      squamous cell carcinoma Hep-2 cells in vitro].
AB  - OBJECTIVE: To detect the effects of ANO1 overexpression on the biological
      behaviors of human laryngeal squamous cell carcinoma Hep-2 cells. METHODS: A Hep
      2 cell line stably overexpressing ANO1 were examined with flow cytometry, soft
      agar assay, wound healing assay, siRNA experiments, and chloride channel block
      with DIDS to observe the effect of ANO1 overexpression on the growth, migration
      and invasion of the cells. RESULTS: Flow cytometry revealed a comparable cell
      percentage in G0/G1 phase between ANO1-overexpressing cells and the control cells
      (P>0.05). The two cells showed no significant difference in soft agar assay
      (P>0.05), but in wound healing experiments, ANO1-overexpressing cells showed
      significantly accelerated migration (P<0.05), whereas siRNA-mediated silencing of
      ANO1 significantly inhibited the cell migration (P<0.05). Treatment with DIDS
      resulted in an effective block of the ANO1 chloride channel activity and
      obviously decreased the migration speed of Hep-2 cells. CONCLUSION: ANO1
      overexpression does not significantly affect the proliferation of cancer cells,
      but can enhance the migration ability of head and neck squamous cell carcinoma,
      suggesting the value of ANO1 as a new gene therapy target for head and neck
      squamous cell carcinoma.

PMID- 24589608
TI  - [Magnetic resonance imaging for pelvic bone marrow fat deposition in patients
      with ankylosing spondylitis].
AB  - OBJECTIVE: To evaluate the diagnostic value of pelvis bone marrow fat depositions
      (BMFD) displayed by magnetic resonance imaging (MRI) in patients with ankylosing
      spondylitis (AS). METHODS: Eighty-eight subjects undergoing pelvic MRI
      examinations were enrolled in this study, including 44 with clinically confirmed
      AS (39 male and 5 female patients with a mean age of 26.41?8.09 years) and 44
      control subjects without AS (37 male and 7 female subjects with a mean age of
      29.32?7.31 years). The incidence of BMFD in the bilateral sacroiliac (SI) joints
      and acetabulum were compared between the two groups. The distribution features of
      BMFD of the periarticular cancellous bone marrow in the pelvis and in other
      regions of the pelvis were analyzed for the AS patients, and the incidence of
      BMFD was determined in different stages of sacroiliitis and hip arthritis.
      RESULTS: The incidence of BMFD in the SI joints and acetabulum was significantly
      higher in the AS patients than in the control subjects (P<0.01); The incidence of
      BMFD was significantly higher in the periarticular cancellous bone marrow than in
      the other positions of pelvis (P<0.01). The incidence of BMFD ranged from 40.0%
      to 45.9% in early stages of sacroiliitis, significantly lower than the incidence
      in later stages (58.3%-73.1%, P<0.01); the incidence showed no difference between
      different stages of hip arthritis (P>0.01). CONCLUSIONS: AS patients have a
      higher incidence of BMFD in the pelvis than control subjects. BMFD is distributed
      mainly under the articular surface, seen throughout the stages of AS, indicating
      that BMFD is an important pathological change of the bone marrow in AS to
      potentially allow early diagnosis of AS.

PMID- 24589609
TI  - [Correlation of follicular fluid human chorionic gonadotrophin level with oocyte
      maturity and early embryonic development].
AB  - OBJECTIVE: To explore the correlation of human chorionic gonadotrophin (hCG)
      level in the follicular fluid on oocyte retrieval day with the number of oocytes
      retrieved, maturation rate, embryonic development, and pregnancy outcome in
      controlled ovarian stimulation cycles. METHODS: The data of 311 IVF/ICSI-ET
      cycles from 2012 to 2013 was analyzed and stratified according to hCG level in
      follicular fluid on oocyte retrieval day (<7 nmol/L, 7-14 nmol/L, 14-21 nmol/L,
      and >21 nmol/L) determined with chemiluminescence method. The number of oocytes
      retrieved, oocyte maturation rate, fertilization rate, cleavage rate, available
      embryo rate and pregnancy rate were compared between the groups. RESULTS: In the
      IVF/ICSI-ET cycles, the cycles with hCG level of 14-21 nmol/L in the follicular
      fluid on the day of oocyte retrieval had significantly higher oocyte maturation
      rate and fertilization rate than those in the other 3 groups (P<0.05), but the
      number of oocytes retrieved, cleavage rate, available embryo rate and pregnancy
      rate, though slightly higher, showed no significant difference from the other 3
      groups (P>0.05). In the group with hCG level >21 nmol/L, the oocyte maturation
      rate and fertilization rate were significantly lower than those in the other 3
      groups (P<0.05), and the available embryo rate and pregnancy rate were slightly
      lower without significant differences from the other 3 groups (P<0.05).
      CONCLUSION: Follicular fluid hCG level on the day of oocyte retrieval is
      associated with oocyte maturation, fertilization, embryonic development
      potential, and IVF outcome. An excessively high follicular fluid hCG level on the
      day of oocyte retrieval may have negative effects on oocyte maturation and embryo
      development.

PMID- 24589610
TI  - [Association of leptin receptor gene polymorphisms with hypertension in Chinese
      population: a meta-analysis].
AB  - OBJECTIVE: To evaluate the association between leptin receptor gene polymorphisms
      and hypertension in Chinese population. METHODS: The keywords "Hypertension",
      "Blood Pressure, high", "Leptin Receptor", "OB Receptor", "LEPR Protein", "CD295
      Antigens", and "LEPR" were used to search the literature to identify the relevant
      studies for meta-analysis using software RevMan 5.0 and Stata 11.0 software.
      RESULTS: Thirteen studies involving 3210 cases of hypertension and 1881 controls
      were included in the meta-analysis. Overall, a significant association was found
      between Gln223Arg gene polymorphism and hypertension in allele contrast and
      dominant genetic model (for allele contrast genetic model: OR=1.17, 95%CI=1.48
      2.15, P<0.0001; for dominant model: OR=2.18, 95%CI=1.75-2.72, P<0.00001). No
      statistically significant correlation was found between Lys109Arg polymorphism
      and hypertension (for allele model: OR=1.13, 95%CI=0.84-1.51, P=0.42; for
      recessive genetic model: OR=0.88, 95%CI=0.33-2.32, P=0.79; for dominant genetic
      model: OR=1.20, 95%CI=0.85-1.71, P=0.29; for additive genetic model: OR=0.90,
      95%CI=0.34-2.42, P=0.84). CONCLUSION: There is no significant correlation between
      Lys109Arg variant of LEPR gene and hypertension in Chinese population, but the
      Gln223Arg polymorphism is associated with hypertension in allele contrast and
      dominant genetic model. Chinese population with an A allele are at a high risk of
      developing hypertension.

PMID- 24589611
TI  - [Short-term therapeutic effect of Endostar combined with chemotherapy for
      advanced colorectal cancer: a meta-analysis].
AB  - OBJECTIVE: To evaluate the safety and efficacy of Endostar combined with
      chemotherapy in the treatment of end-stage colorectal cancer. METHODS: s The
      relevant randomized controlled trials were retrieved from the electronic
      databases of Cochrane library, PubMed, EMbase, CNKI, CBM, VIP and Chinese Medical
      Association. The retrieval time limit was from the database construction to
      January 2013. The data were extracted from eligible studies assessed for
      methodological quality according to Cochrane handbook for systematic reviews and
      analyzed using RevMan 5.2 software. RESULTS: Five randomized controlled trials
      involving 220 cases were included for meta-analysis. The results showed that
      Endostar combined with chemotherapy had an overall advantage over chemotherapy
      alone in terms of complete response rate (10.91% vs 2.73% RR=4.08, 95% CI: 1.19
      13.95, P=0.02), partial response rate (48.18% vs 30.91% RR=2.18, 95% CI: 1.23
      3.87, P=0.007), progressive disease (15.45% vs 41.82% RR=0.25, 95% CI: 0.13-0.47,
      P<0.0001), and the response rate (60.00% vs 33.64% RR=3.23, 95% CI: 1.79-5.81,
      P<0.0001). Clinical benefit response(82.73% vs 55.45% RR=4.30,95% CI:1.19-13.95,
      P<0.0001). The main adverse reactions included nausea, vomiting, constipation,
      palpitation, and electrocardiogram changes. CONCLUSION: Endostar combined with
      chemotherapy is effective for advanced colorectal cancer and can be used as a
      routine treatment.

PMID- 24589612
TI  - [Correlation between adipocytokines levels and metabolic syndrome in type 2
      diabetes mellitus].
AB  - OBJECTIVE: To study the correlation between adipocytokines levels and metabolic
      syndrome (MS) in patients with newly diagnosed type 2 diabetes mellitus (T2DM).
      METHODS: Sixty-eight patients with newly diagnosed T2DM, including 51 cases with
      MS and 17 without MS, were examined for blood pressure (BP), fasting blood
      glucose (FBG), fasting insulin (FINS), insulin resistance index (IRI), waist to
      hip ratio (W/H), body mass index (BMI), and serum adipocytokine levels (IL-6,
      vaspin, and adiponectin). RESULTS: The diabetic patients with MS had higher BMI,
      HbA1c, FBG, FINS, IRI, TG, TC, and SBP than those without MS. Serum IL-6 level
      was higher but adiponectin level was lower in patients with MS than in those
      without MS. There was no significant difference in vaspin level between the two
      groups. Adiponectin level was positively correlated with TG (r=-0.30, P=0.02) and
      inversely with BMI (r=-0.47, P=0.39) and HOMA-IR (r=-0.30, P=0.03); vaspin level
      was positively correlated with HOMA-IR (r=0.347, P=0.02) and inversely with HDL-L
      (r=-0.45, P=0.01); IL-6 level was positively correlated with LDL-L (r=0.18,
      P=0.25) and inversely with HDL-L (r=-0.45, P=0.01). CONCLUSION: Adiponectin and
      IL-6 levels are closely related to MS, but the relationship between vaspin and MS
      needs further investigation.

PMID- 24589613
TI  - [Research process of the neuropeptide VGF as a novel antidepressant regulatory
      factor].
AB  - As a major cause of disability, depression is expected to become the second
      highest burden of disease worldwide by the year 2020. The shift of research in
      depression from monoamine hypothesis to the realm of neurotrophic hypothesis,
      neural plasticity hypothesis, and enhancing neurogenesis as an antidepressant
      like agent brings about crucial insights to find novel mediator of antidepressant
      activity. Studies have shown that the neuropeptide VGF participates in the
      regulation of hippocampal neurogenesis and neuroplasticity and also plays an
      important role in the regulation of neuronal proliferation and survival,
      suggesting that the neuropeptide VGF may be a novel regulator in antidepressant
      treatment. The authors review the latest progress in the regulatory mechanisms of
      neuropeptide VGF on neurogenesis, neurotrophic and synaptic activity in
      depression. Further understanding of the role of neuropeptide VGF in depression
      can identify novel targets for pharmacological interventions.

PMID- 24589614
TI  - [Factors affecting the quality of life of elderly diabetic patients: survey in
      north and south Wanjiang river regions].
AB  - OBJECTIVE: To investigate the quality of life of elderly diabetic patients and
      its influencing factors. METHODS: By randomized cluster sampling, we conducted a
      survey in 1450 elderly residents (over 60 years old) living in urban, suburban
      and rural areas in south and north Anhui province. We evaluated the quality of
      life of the elderly diabetic patients using a demographic information
      questionnaire and full items on Short Form (36) Health Survey (SF-36). RESULTS:
      The elderly diabetic patients had lower scores in all dimensions of quality of
      life than the elderly without diabetes. Multiple linear regression analysis
      showed a linear regression in the quality of life among the elderly diabetic
      patients in terms of geographic regions, education, personality, sleep quality,
      and age. CONCLUSION: Elderly diabetic patients have generally poor quality of
      life, which was subjected to the influences by geographic regions, education,
      personality, sleep quality, and age, suggesting the necessity of corresponding
      interventions to improve the quality of life of these patients.

PMID- 24589615
TI  - [Shielding effect of distance in (131)I-131 therapy for differentiated thyroid
      cancer].
AB  - OBJECTIVE: To investigate the shielding effect of distance in radioactive iodine
      treatment in patients with differentiated thyroid cancer (DTC). METHODS: Eighty
      seven DTC patients underwent postoperative radioactive iodine treatment at the
      therapeutic doses ranging from 2.96 GBq to 7.4 GBq. The patients were divided
      into two groups to receive high-dose therapy (>=3.7 GBq, 48 patients) and low
      dose therapy (<3.7 GBq, 39 patients). The radiation doses at 0.05 m, 1 m, and 3 m
      were recorded at different days; the doses at 1 m and 3 m on the third day, the
      dose of standard radioactivity source of 1.11GBq (131)I, and the natural
      background radioactivity were also recorded. RESULTS: The radiation dose at a 1
      meter distance was significantly higher in the high-dose group than in the low
      dose group (P<0.05). The radiation doses in different dose groups at the other
      distances or at different time points showed no significant differences (P>0.05).
      On the third day after therapy, the radiation dose at 1 m was significantly lower
      than the reference radioactivity source of 1.11 GBq (131)I (P=0.000), but still
      higher than the natural background radioactivity at 3 m (P=0.000). CONCLUSION: In
      DTC patients who receive radioactive iodine therapy, the radioactive radiation
      dose decreases rapidly after 3 days. The radioactive radiation dose on the third
      day is significantly lower than the reference radioactive radiation dose, so that
      the patients can be discharged with safety for contact at a distance beyond one
      meter.

PMID- 24589616
TI  - [Rare prostate metastasis of lung adenocarcinoma: a case report and literature
      review].
AB  - Hematogenous metastasis is common in lung cancer, and except for small cell lung
      cancer and melanoma, tumors with extensive metastasis seldom involve the
      prostate. The treatment of lung adenocarcinoma with prostate metastasis relies
      mainly on systemic chemotherapy with rigorous treatment of the primary lesions
      and metastatic palliative radiotherapy. Comprehensive treatment integrating
      traditional Chinese medicine may improve the quality of life of the patients. 

PMID- 24589617
TI  - Loss of proteostasis induced by amyloid beta peptide in brain endothelial cells.
AB  - Abnormal accumulation of amyloid-beta (Abeta) peptide in the brain is a
      pathological hallmark of Alzheimer's disease (AD). In addition to neurotoxic
      effects, Abeta also damages brain endothelial cells (ECs) and may thus contribute
      to the degeneration of cerebral vasculature, which has been proposed as an early
      pathogenic event in the course of AD and is able to trigger and/or potentiate the
      neurodegenerative process and cognitive decline. However, the mechanisms
      underlying Abeta-induced endothelial dysfunction are not completely understood.
      Here we hypothesized that Abeta impairs protein quality control mechanisms both
      in the secretory pathway and in the cytosol in brain ECs, leading cells to death.
      In rat brain RBE4 cells, we demonstrated that Abeta1-40 induces the failure of
      the ER stress-adaptive unfolded protein response (UPR), deregulates the ubiquitin
      proteasome system (UPS) decreasing overall proteasome activity with accumulation
      of ubiquitinated proteins and impairs the autophagic protein degradation pathway
      due to failure in the autophagic flux, which culminates in cell demise. In
      conclusion, Abeta deregulates proteostasis in brain ECs and, as a consequence,
      these cells die by apoptosis. 

PMID- 24589618
TI  - Statins for all.

PMID- 24589619
TI  - To phosphorylate or not to phosphorylate: Selective alterations in tyrosine
      kinase-inhibited EphB mutant mice.
AB  - EphB tyrosine kinase receptors have been implicated in multiple developmental
      processes; however, the signaling mechanism underlying these events remains
      unclear. Through a triple knock-in mouse line for three neurally expressed EphBs,
      Sokis et al. demonstrated that EphB tyrosine kinase activity is required for axon
      guidance but does not influence synapse formation. This short communication
      highlights their study and appealing molecular approach that elucidated the
      functions of EphB tyrosine kinase during developmental events. 

PMID- 24589620
TI  - Semaphorin 3A: A new player in bone remodeling.
AB  - Semaphorin 3A (Sema3A) is a protein identified originally as a diffusible axonal
      chemorepellent. Sema3A has multifunctional roles in embryonic development, immune
      regulation, vascularization, and oncogenesis. Bone remodeling consists of two
      phases: the removal of mineralized bone by osteoclasts and the formation of new
      bone by osteoblasts, and plays an essential role in skeletal diseases such as
      osteoporosis. Recent studies have shown that Sema3A is implicated in the
      regulation of osteoblastgenesis and osteoclastgenesis. Moreover, low bone mass in
      mice with specific knockout of Sema3A in the neurons indicates that Sema3A
      regulates bone remodeling indirectly. This review highlights recent advances on
      our understanding of the role of sema3A as a new player in the regulation of bone
      remodeling and proposes the potential of sema3A in the diagnosis and therapy of
      bone diseases.

PMID- 24589621
TI  - Emerging role for nuclear rotation and orientation in cell migration.
AB  - Nucleus movement, positioning, and orientation is precisely specified and
      actively regulated within cells, and it plays a critical role in many cellular
      and developmental processes. Mutation of proteins that regulate the nucleus
      anchoring and movement lead to diverse pathologies, laminopathies in particular,
      suggesting that the nucleus correct positioning and movement is essential for
      proper cellular function. In motile cells that polarize toward the direction of
      migration, the nucleus undergoes controlled rotation promoting the alignment of
      the nucleus with the axis of migration. Such spatial organization of the cell
      appears to be optimal for the cell migration. Nuclear reorientation requires the
      cytoskeleton to be anchored to the nuclear envelope, which exerts pulling or
      pushing torque on the nucleus. Here we discuss the possible molecular mechanisms
      regulating the nuclear rotation and reorientation and the significance of this
      type of nuclear movement for cell migration. 

PMID- 24589622
TI  - E3 ubiquitin ligases in regulating stress fiber, lamellipodium, and focal
      adhesion dynamics.
AB  - Recent discoveries have unveiled the roles of a complicated network of E3
      ubiquitin ligases in regulating cell migration machineries. The E3 ubiquitin
      ligases Smurf1 and Cul/BACURD ubiquitinate RhoA to regulate stress fiber
      formation and cell polarity, and ASB2alpha ubiquitinates filamins to modulate
      cytoskeletal stiffness, thus regulating cell spreading and cell migration. HACE1,
      XIAP, and Skp1-Cul1-F-box bind to Rac1 and cause its ubiquitination and
      degradation, thus suppressing lamellipodium protrusions, while PIAS3, a SUMO
      ligase, activates Rac1 to promote lamellipodium dynamics. Smurf1 also enhances
      Rac1 activation but it does not ubiquitinate Rac1. Both Smurf1 and HECTD1
      regulate focal adhesion (FA) assembly and (or) disassembly through ubiquitinating
      the talin head domain and phosphatidylinositol 4 phosphate 5-kinase type I gamma
      (PIPKIgamma90), respectively. Thus, E3 ubiquitin ligases regulate stress fiber
      formation, cell polarity, lamellipodium protrusions, and FA dynamics through
      ubiquitinating the key proteins that control these processes.

PMID- 24589623
TI  - Recombinant disintegrin targets alpha(v) beta(3) integrin and leads to mediator
      production.
AB  - Integrin alphavbeta3 is most likely the foremost modulator of angiogenesis among
      all known integrins. Recombinant disintegrin DisBa-01, originally obtained from
      snake venom glands, binds to alphavbeta3, thereby significantly inhibiting
      adhesion and generating in vivo anti-metastatic ability. However, its function in
      mediator production is not clear. Here, we observed that the mediators VEGF-A, IL
      8, and TGF-beta are not produced by human umbilical vein endothelial cells (HUVEC
      cell line) or monocyte/macrophage cells (SC cell line) when cells adhered to
      vitronectin. However, when exposed to DisBa-01, HUVECs produced higher levels of
      TGF-beta, and SC cells produced higher levels of VEGF-A. Nonetheless, HUVECs also
      showed an enhancement of apoptosis after losing adherence when exposed to
      disintegrin, which is a characteristic of anoikis. We propose that disintegrin
      DisBa-01 could be used to modulate integrin alphavbeta3 functions.

PMID- 24589625
TI  - High-performance flexible ultraviolet photoconductors based on solution-processed
      ultrathin ZnO/Au nanoparticle composite films.
AB  - Transparent ultraviolet (UV) ZnO thin film photoconductors are expected to have
      great applications in environmental monitoring, large-area displays, and optical
      communications, and they have drawn enormous interests in recent years. However,
      at present their performances are not satisfactory: the responsivity R (a
      parameter characterizing the sensitivity of the device to light) is not high
      (<1.0 * 10(3) AW(-1)), and the transparency T is not high either (<80%).
      Realizing high R and high T remains a big challenge today. In this paper, by
      employing solution-processed ultrathin ZnO/Au nanoparticle composite films, R as
      high as 1.51 * 10(5) AW(-1) and T of over 90% are achieved. High values for
      detectivity D* and linear dynamic range LDR are also obtained, which are 2.05 *
      10(15) Jones and 60 dB, respectively. Moreover, such high-performance devices can
      be fabricated on flexible PET (polyethylene terephthalate) substrates. 

PMID- 24589624
TI  - A combinatorial mutagenesis approach for functional epitope mapping on phage
      displayed target antigen: application to antibodies against epidermal growth
      factor.
AB  - Although multiple different procedures to characterize the epitopes recognized by
      antibodies have been developed, site-directed mutagenesis remains the method of
      choice to define the energetic contribution of antigen residues to binding. These
      studies are useful to identify critical residues and to delineate functional maps
      of the epitopes. However, they tend to underestimate the roles of residues that
      are not critical for binding on their own, but contribute to the formation of the
      target epitope in an additive, or even cooperative, way. Mapping antigenic
      determinants with a diffuse energetic landscape, which establish multiple
      individually weak interactions with the antibody paratope, resulting in high
      affinity and specificity recognition of the epitope as a whole, is thus
      technically challenging. The current work was aimed at developing a combinatorial
      strategy to overcome the limitations of site-directed mutagenesis, relying on
      comprehensive randomization of discrete antigenic regions within phage-displayed
      antigen libraries. Two model antibodies recognizing epidermal growth factor were
      used to validate the mapping platform. Abrogation of antibody recognition due to
      the introduction of simultaneous replacements was able to show the involvement of
      particular amino acid clusters in epitope formation. The abundance of some of the
      original residues (or functionally equivalent amino acids sharing their
      physicochemical properties) among the set of mutated antigen variants selected on
      a given antibody highlighted their contributions and allowed delineation of a
      detailed functional map of the corresponding epitope. The use of the
      combinatorial approach could be expanded to map the interactions between other
      antigens/antibodies. 

PMID- 24589626
TI  - Probing the effect of surface chemistry on the electrical properties of ultrathin
      gold nanowire sensors.
AB  - Ultrathin metal nanowires are ultimately analytical tools that can be used to
      survey the interfacial properties of the functional groups of organic molecules
      immobilized on nanoelectrodes. The high ratio of surface to bulk atoms makes such
      ultrathin nanowires extremely electrically sensitive to adsorbates and their
      charge and/or polarity, although little is known about the nature of surface
      chemistry interactions on metallic ultrathin nanowires. Here we report the first
      studies about the effect of functional groups of short-chain alkanethiol
      molecules on the electrical resistance of ultrathin gold nanowires. We fabricated
      ultrathin nanowire electrical sensors based on chemiresistors using conventional
      microfabrication techniques, so that the contact areas were passivated to leave
      only the surface of the nanowires exposed to the environment. By immobilizing
      alkanethiol molecules with head groups such as -CH3, -NH2 and -COOH on gold
      nanowires, we examined how the charge proximity due to protonation/deprotonation
      of the functional groups affects the resistance of the sensors. Electrical
      measurements in air and in water only indicate that beyond the gold-sulfur moiety
      interactions, the interfacial charge due to the acid-base chemistry of the
      functional groups of the molecules has a significant impact on the electrical
      resistance of the wires. Our data demonstrate that the degree of dissociation of
      the corresponding functional groups plays a major role in enhancing the surface
      sensitive resistivity of the nanowires. These results stress the importance of
      recognizing the effect of protonation/deprotonation of the surface chemistry on
      the resulting electrical sensitivity of ultrathin metal nanowires and the
      applicability of such sensors for studying interfacial properties using
      electrodes of comparable size to the electrochemical double layer. 

PMID- 24589627
TI  - Identification of dermatophyte species using genomic in situ hybridization
      (GISH).
AB  - A genomic in situ hybridization (GISH)-based method for dermatophyte
      identification has been developed. Using specific GISH probes, discrimination
      between Trichophyton interdigitale, Trichophyton rubrum and Microsporum canis has
      been conducted. Moreover, GISH has been found particularly helpful when proper
      dermatophyte identification was difficult due to ambiguous PCR-RFLP patterns. 

PMID- 24589628
TI  - Synthesis of polycyclic substituted vinylarenes via a one-pot intramolecular aryl
      alkylation-N-tosylhydrazone insertion reaction.
AB  - A novel method of a palladium-catalyzed/norbornene-mediated intramolecular C-H
      activation/N-tosylhydrazones insertion reaction is developed. In this process,
      various bicyclic or tricyclic substituted vinylarenes are obtained with high
      efficiency under mild conditions. 

PMID- 24589629
TI  - Variable maternal methylation overlapping the nc886/vtRNA2-1 locus is locked
      between hypermethylated repeats and is frequently altered in cancer.
AB  - Cancer is as much an epigenetic disease as a genetic one; however, the interplay
      between these two processes is unclear. Recently, it has been shown that a large
      proportion of DNA methylation variability can be explained by allele-specific
      methylation (ASM), either at classical imprinted loci or those regulated by
      underlying genetic variants. During a recent screen for imprinted differentially
      methylated regions, we identified the genomic interval overlapping the non-coding
      nc886 RNA (previously known as vtRNA2-1) as an atypical ASM that shows variable
      levels of methylation, predominantly on the maternal allele in many tissues. Here
      we show that the nc886 interval is the first example of a polymorphic imprinted
      DMR in humans. Further analysis of the region suggests that the interval
      subjected to ASM is approximately 2 kb in size and somatically acquired. An in
      depth analysis of this region in primary cancer samples with matching normal
      adjacent tissue from the Cancer Genome Atlas revealed that aberrant methylation
      in bladder, breast, colon and lung tumors occurred in approximately 27% of cases.
      Hypermethylation occurred more frequently than hypomethylation. Using additional
      normal-tumor paired samples we show that on rare occasions the aberrant
      methylation profile is due to loss-of-heterozygosity. This work therefore
      suggests that the nc886 locus is subject to variable allelic methylation that
      undergoes cancer-associated epigenetic changes in solid tumors. 

PMID- 24589631
TI  - Six weeks of unsupervised Nintendo Wii Fit gaming is effective at improving
      balance in independent older adults.
AB  - OBJECTIVE: To determine the effectiveness of unsupervised Nintendo Wii Fit
      balance training in older adults. METHODS: Forty-one older adults were recruited
      from local retirement villages and educational settings to participate in a six
      week two-group repeated measures study. The Wii group (n = 19, 75 +/- 6 years)
      undertook 30 min of unsupervised Wii balance gaming three times per week in their
      retirement village while the comparison group (n = 22, 74 +/- 5 years) continued
      with their usual exercise program. Participants' balance abilities were assessed
      pre- and postintervention. RESULTS: The Wii Fit group demonstrated significant
      improvements (P < .05) in timed up-and-go, left single-leg balance, lateral reach
      (left and right), and gait speed compared with the comparison group. Reported
      levels of enjoyment following game play increased during the study. CONCLUSION:
      Six weeks of unsupervised Wii balance training is an effective modality for
      improving balance in independent older adults.

PMID- 24589630
TI  - Association of a television in the bedroom with increased adiposity gain in a
      nationally representative sample of children and adolescents.
AB  - IMPORTANCE: Obesity affects health in children and adolescents. Television
      viewing is an established risk factor for obesity in youth. No prospective study
      has assessed whether a bedroom television confers an additional risk for obesity
      in youth. OBJECTIVE: To assess the prospective association between the presence
      of a bedroom television and change in body mass index (BMI; calculated as weight
      in kilograms divided by height in meters squared), independent of television
      viewing, in a nationally representative sample of US children and adolescents.
      DESIGN, SETTING, AND PARTICIPANTS: We conducted a random-digit prospective
      telephone survey that captured children and adolescents from across the United
      States. Participants included 6522 boys and girls aged 10 to 14 years at baseline
      who were surveyed via telephone about media risk factors for obesity.Weighted
      regressions assessed adiposity at 2- and 4-year follow-up, controlling for
      television and movie viewing, video-game playing, parenting, age, sex, race or
      ethnicity, household income, and parental educational level. EXPOSURE: Report of
      having a television in the bedroom at baseline. MAIN OUTCOMES AND MEASURES: Age-
      and sex-adjusted BMI based on self-report and parent report of weight and height
      at 2- and 4-year follow-up. RESULTS: Distributions for age, sex, race or
      ethnicity, and socioeconomic status were similar to census estimates for the US
      population. Sample weighting methods accounted for higher dropout rates among
      ethnic minorities and those with lower socioeconomic status. Bedroom televisions
      were reported by 59.1%of participants at baseline, with boys, ethnic minorities,
      and those of lower socioeconomic status having significantly higher rates. In
      multivariate analyses, having a bedroom television was associated with an excess
      BMI of 0.57 (95%CI, 0.31-0.82) and 0.75 (0.38-1.12) at years 2 and 4,
      respectively, and a BMI gain of 0.24 (0.02-0.45) from years 2 to 4. CONCLUSIONS
      AND RELEVANCE: Having a bedroom television is associated with weight gain beyond
      the effect of television viewing time. This association could be the result of
      uncaptured effects of television viewing or of disrupted sleep patterns. With the
      high prevalence of bedroom televisions, the effect attributable to this risk
      factor among US children and adolescents is excess weight of 8.7 million kg/y.

PMID- 24589632
TI  - Measuring community integration using Geographic Information Systems (GIS) and
      participatory mapping for people who were once homeless.
AB  - Measures of community integration rely on self-report assessments that often
      quantify physical or social participation, but fail to capture the individual's
      spatial presence in the community. The current study documents the activity
      space, or area of daily experiences, of 37 individuals who were once homeless
      through participatory mapping and Geographic Information Systems (GIS). Contrary
      to expectations, there was no significant relationship between activity space
      size and community integration measures, except a negative association with
      physical integration. Further analysis revealed, however, that continued use of
      homeless services, geographically spread throughout the city, was associated with
      larger activity space size, but may be counterproductive to social and
      psychological integration efforts. Analysis of the types of locations identified
      revealed high importance given to leisure locations and ongoing involvement with
      medical and mental health locations. Finally, community integration outcomes did
      not differ significantly by demographics or housing type, but rather degree of
      family involvement and feeling like home, factors that may have more potential
      for change. 

PMID- 24589633
TI  - Expression of growth factors and growth factor receptors in human cleft-affected
      tissue.
AB  - OBJECTIVE. To investigate cleft disordered tissue in children with cleft palate
      and cleft lip with or without alveolar clefting for detection of local tissue
      growth factors and growth factor receptors and compare findings. Design.
      Morphological analysis of human tissue. Patients. Three groups were studied: 14
      patients with cleft palate at the age from eight months to 18 years and two
      months, 12 patients with cleft lip with or without alveolar clefting in the age
      from four months to 15 years and four months and 11 control patients. RESULTS. In
      general, cleft palate disordered tissue showed more prominent expression of
      BMP2/4 (z=3.574; p=0.0004) and TGFbeta (z=2.127; p=0.033), while expression of
      TGFBR3 significantly higher was only in connective tissue (z=3.822; p=0.0001).
      Cleft lip affected tissue showed significantly pronounced expression of FGFR1 in
      general as well as separately in epithelium. CONCLUSIONS. The marked and
      statistically significant expression of BMP 2/4 in cleft palate disordered soft
      tissue probably is delayed, but still proliferation and differentiation as well
      as tissue, especially, bone remodeling contributing signal. Cleft palate affected
      tissue show more prominent expression of TGFbeta, still the weak regional
      expression of TGFbeta type III receptors prove the disordered tissue growth and
      changed TGFbeta signalling pathway in postnatal pathogenesis. In general,
      expression of TGFbeta, BMP 2/4 and FGFR1 is significantly different, giving
      evidence to the involvement of these mentioned factors in the cleft severity
      morphopathogenesis. 

PMID- 24589634
TI  - Radiographic assessment of findings in the maxillary sinus using cone-beam
      computed tomography.
AB  - OBJECTIVES. To assess the presence of anatomic variations and pathology of the
      maxillary sinus using cone beam computed tomography (CBCT) of the maxilla where
      pre- implant surgery is planned. MATERIAL AND METHODS. This retrospective study
      evaluates a sample CBCT scans of 34 dental patients (68 sinuses). CBCT is used to
      assess maxillary sinus mucosa and outflow and prevalence of septa. The mucosal
      thickening was measured and the sinus outflow was classified as open or
      obstructed. RESULTS. Mucosal thickening was found in 48.5%, septa in 20.6% and
      total opacity in 2.9% of the sinuses. Maxillary sinus outflow was blocked in
      26.5% of the scans. Strong association between radiological signs of maxillary
      sinus ostium blockage and thickened mucosa was observed. CONCLUSIONS. Anatomic
      variations and lesions of the maxillary sinus were common findings in CBCT
      examinations of the maxilla required for dental preprosthetic planning. Routine
      CBCT scans, including maxillary sinus ostium are recommended for risk assessment
      prior to surgery. 

PMID- 24589635
TI  - Influence of restorative techniques on fracture load of endodontically treated
      premolars.
AB  - OBJECTIVE. This study evaluated the influence of restorative techniques on the
      fracture load and fracture mode of endodontically treated premolars with MOD
      cavities. MATERIALS AND METHODS: Sixty maxillary premolars were divided into
      groups: G1 - sound teeth; G2 - direct technique using Four Season; G3 - Adoro
      inlays; G4 - Adoro onlays; G5 - Empress inlays; G6 - Empress onlays. The
      specimens were submitted to compressive axial loading until failure. The fracture
      mode was analyzed. RESULTS. According to ANOVA and Tukey's test (alpha=0.05), the
      sound teeth (1370.61 N) showed the highest fracture load mean, which did not
      differ statistically from IPS Empress onlays (1304.21 N). Intermediate values
      were obtained for IPS Empress inlays (918.76 N), Adoro onlays (861.15 N), Adoro
      inlays (792.71 N) which did not differ statistically among them. The lowest
      fracture load was obtained for direct restorations with Four Seasons (696.08 N),
      which did not differ statistically from the Adoro inlays. CONCLUSIONS. The
      ceramic restorations provided higher fracture load and more incidences of
      catastrophic fractures. Cuspal coverage increased teeth fracture load. The
      results were similar for direct and indirect inlays with composite resin.

PMID- 24589636
TI  - Apoptosis and MMP-2, TIMP-2 expression in cleft lip and palate.
AB  - Aim of our study was complex detection of appearance and distribution of specific
      signalling proteins and apoptosis in facial tissue of children with complete
      bilateral cleft lip and palate (CBCLP). MATERIALS AND METHODS. Nineteen CBCLP
      patients and 11 unaffected subjects were involved in this study. All the tissue
      samples were proceeded for detection of matrix metalloproteinase-2 (MMP-2),
      tissue inhibitor of matrix metalloproteinase-2 (TIMP-2), and apoptosis. The
      intensity of immunostaining was graded semi-quantitatively. Results of the
      terminal deoxynucleotidyl transferase mediated dUTP nick-end labeling (TUNEL)
      method were obtained by counting apoptosis positive cells in five unintentionally
      chosen fields of vision. Groups were compared using the Mann-Whitney test.
      RESULTS. TUNEL-positive oral epithelial cells were significantly increased in the
      control group when compared with the CBCLP group. Connective tissue cells have a
      statistically significant lower expression of TIMP-2 in the control group
      compared to the CBCLP group. CONCLUSIONS. TIMP-2 positive connective tissue cells
      increasingly found in oral mucosa lamina propria proves the decrease of local
      apoptosis in CLP patients. Prominent expression of MMP-2 in cleft affected soft
      tissue indicates a possible increase of tissue remodelling. 

PMID- 24589637
TI  - Toothache among dental patients attending a Nigerian secondary healthcare
      setting.
AB  - INTRODUCTION. Pain intensity and oral health practices among patients with
      toothache, a major dental public health problem is necessary information for the
      formulation of preventive and interventional oral health policies. OBJECTIVE. To
      assess the pain intensity and oral health practices among dental patients
      attending a Nigerian secondary healthcare setting with toothache. MATERIALS AND
      METHODS. This study was a prospective study of adult patients attending the
      dental clinic of Rasheed Shekoni Specialist Hospital, Dutse, Jigawa State,
      Nigeria. Interviewer-administered questionnaire which elicited information
      include demography, pain intensity using visual analogue, tooth brushing
      behaviour and previous dental treatment was the tool of data collection. RESULTS.
      The majority of the respondents were males and young adults. More than half
      (60.5%) of the respondents reported pain of moderate to severe intensity and
      42.6% have engaged in self medication for the toothache. More than one-third
      (34.2%) had experienced the pain for >= four weeks and the major factor that
      prompted the decision to visit dentist were unbearable nature of the pain and
      sleep disturbances. Almost half (46.2%) of the respondents had previously visited
      the dentist and the common received treatment was tooth extraction. A total of
      57.9% of the respondents indulge in twice-daily tooth cleaning. CONCLUSION. Data
      from this study revealed that respondents with toothache had history of dental
      visit and visited dental clinic when the pain is unbearable and disturbed sleep.
      There is a need for proper patient education at any encounter with dentist. 

PMID- 24589638
TI  - Stro-1-positive BMSCs predict postoperative periprosthetic bone mineral density
      outcomes in uncemented total hip arthroplasty patients.
AB  - BACKGROUND: Bone marrow cell profiles are variable after total hip arthroplasty
      (THA), including variable levels of Stro-1+ and bone morphogenetic protein
      receptor (BMPRs)+ cells. We investigated the impact of bone marrow cell profiles
      on changes in periprosthetic bone mineral density (BMD) in uncemented THA
      patients. MATERIAL AND METHODS: Bone marrow aspirates were collected from the
      metaphyseal region of discarded femoral heads from 24 consecutive THA patients
      (12 men and 12 women; mean age 66.7 +/- 11.0 years; range 52-87 years) treated
      from March 2009 to March 2011 at a single facility. Perioperative proportions of
      Stro-1+ and BMPR+ cells in femoral heads were assessed by flow cytometry. Follow
      up examined the proximal femur Gruen zones R1 and R7 at 1 week and at 3, 6, and
      12 months after THA, using dual-energy X-ray absorptiometry. Associations between
      BMD loss and age, gender, BMPRs+, and Stro-1+ were analyzed. RESULTS: At 3
      months, R1 and R7 BMD decreased by 4.4% and 6.4%, respectively (P<0.05). At 12
      months, the overall BMD decreases in R1 and R7 were 10.2% and 1%, respectively
      (P<0.05). Higher Stro-1+ cells proportion predicted R7 BMD increases at all time
      points (P<0.05) and R1 BMD increases at 6 and 12 months (P<0.05). BMPR1a+
      proportion was associated with BMD increases at 6 months in the R1 region. BMPR2+
      was not significantly associated with BMD (P>0.05). CONCLUSIONS: Elevated Stro-1+
      bone marrow cell profile may be a useful prognostic indicator for uncemented THA
      patients.

PMID- 24589640
TI  - Corticosteroids and transition to delirium in patients with acute lung injury.
AB  - OBJECTIVE: Delirium is common in mechanically ventilated patients in the ICU and
      associated with short- and long-term morbidity and mortality. The use of systemic
      corticosteroids is also common in the ICU. Outside the ICU setting,
      corticosteroids are a recognized risk factor for delirium, but their relationship
      with delirium in critically ill patients has not been fully evaluated. We
      hypothesized that systemic corticosteroid administration would be associated with
      a transition to delirium in mechanically ventilated patients with acute lung
      injury. DESIGN: Prospective cohort study. SETTING: Thirteen ICUs in four
      hospitals in Baltimore, MD. PATIENTS: Five hundred twenty mechanically ventilated
      adult patients with acute lung injury. INTERVENTIONS: None. MEASUREMENTS AND MAIN
      RESULTS: Delirium evaluation was performed by trained research staff using the
      validated Confusion Assessment Method for the ICU screening tool. A total of 330
      of the 520 patients (64%) had at least two consecutive ICU days of observation in
      which delirium was assessable (e.g., patient was noncomatose), with a total of
      2,286 days of observation and a median (interquartile range) of 15 (9, 28)
      observation days per patient. These 330 patients had 99 transitions into delirium
      from a prior nondelirious, noncomatose state. The probability of transitioning
      into delirium on any given day was 14%. Using multivariable Markov models with
      robust variance estimates, the following factors (adjusted odds ratio; 95% CI)
      were independently associated with transition to delirium: older age (compared to
      < 40 years old, 40-60 yr [1.81; 1.26-2.62], and >= 60 yr [2.52; 1.65-3.87]) and
      administration of any systemic corticosteroid in the prior 24 hours (1.52; 1.05
      2.21). CONCLUSIONS: After adjusting for other risk factors, systemic
      corticosteroid administration is significantly associated with transitioning to
      delirium from a nondelirious state. The risk of delirium should be considered
      when deciding about the use of systemic corticosteroids in critically ill
      patients with acute lung injury.

PMID- 24589641
TI  - The process of prehospital airway management: challenges and solutions during
      paramedic endotracheal intubation.
AB  - OBJECTIVES: Endotracheal intubation success rates in the prehospital setting are
      variable. Our objective was to describe the challenges encountered and corrective
      actions taken during the process of endotracheal intubation by paramedics.
      DESIGN: Analysis of prehospital airway management using a prospective registry
      that was linked to an emergency medical services administrative database.
      SETTING: Emergency medical services system serving King County, Washington, 2006
      2011. Paramedics in this system have the capability to administer neuromuscular
      blocking agents to facilitate intubation (i.e., rapid sequence intubation).
      PATIENTS: A total of 7,523 patients more than 12 years old in whom paramedics
      attempted prehospital endotracheal intubation. INTERVENTIONS: None. MEASUREMENTS
      AND MAIN RESULTS: An intubation attempt was defined as the introduction of the
      laryngoscope into the patient's mouth, and the attempt concluded when the
      laryngoscope was removed from the mouth. Endotracheal intubation was successful
      on the first attempt in 77% and ultimately successful in 99% of patients (7,433
      of 7,523). Paramedics used a rapid sequence intubation strategy on 54% of first
      attempts. Among the subset with a failed first attempt (n = 1,715), bodily fluids
      obstructing the laryngeal view (50%), obesity (28%), patient positioning (17%),
      and facial or spinal trauma (6%) were identified as challenges to intubation. A
      variety of adjustments were made to achieve intubation success, including upper
      airway suctioning (used in 43% of attempts resulting in success), patient
      repositioning (38%), rescue bougie use (19%), operator change (16%), and rescue
      rapid sequence intubation (6%). Surgical cricothyrotomy (0.4%, n = 27) and bag
      valve-mask ventilation (0.8%, n = 60) were rarely performed by paramedics as
      final rescue airway strategies. CONCLUSIONS: Airway management in the prehospital
      setting has substantial challenges. Success can require a collection of
      adjustments that involve equipment, personnel, and medication often in a
      simultaneous fashion.

PMID- 24589642
TI  - Deriving consensus on the characteristics of advanced practice nursing: meta
      summary of more than 2 decades of research.
AB  - BACKGROUND: Over recent decades, there has been considerable research and debate
      about essential features of advanced nursing practice and differences among
      various categories of advanced practice nurses. OBJECTIVES: This study aimed to
      derive an integrative description of the defining characteristics of advanced
      practice nursing through a meta-summary of the existing literature. METHODS: A
      three-phase approach involved (a) systematic review of the literature to identify
      the specific activities characterized as advanced practice nursing, (b)
      qualitative meta-summary of practice characteristics extracted from manuscripts
      meeting inclusion criteria; and (c) statistical analysis of domains across
      advanced practice categories and country in which the study was completed. A
      descriptive framework was distilled using qualitative and quantitative results.
      RESULTS: Fifty manuscripts met inclusion criteria and were retained for analysis.
      Seven domains of advanced nursing practice were identified: (a) autonomous or
      nurse-led extended clinical practice; (b) improving systems of care; (c)
      developing the practice of others; (d) developing/delivering educational
      programs/activities; (e) nursing research/scholarship; (f) leadership external to
      the organization; and (g) administering programs, budgets, and personnel. Domains
      were similar across categories of advanced nursing practice; the domain of
      developing/delivering educational programs/activities was more common in
      Australia than in the United States or United Kingdom. DISCUSSION: Similarity at
      the domain level was sufficient to suggest that advanced practice role categories
      are less distinct than often argued. There is merit in adopting a more integrated
      and consistent interpretation of advanced practice nursing.

PMID- 24589643
TI  - Registration of nurse-initiated clinical trials: why, how, when?

PMID- 24589644
TI  - Skeletal muscle troponin as a novel biomarker to enhance assessment of the impact
      of strength training on fall prevention in the older adults.
AB  - BACKGROUND: Loss of muscle mass and strength (i.e., sarcopenia) in the older
      adults is a strong predictor of falls, with subsequent morbidity and inability to
      execute activities of daily living. Use of biomarkers may enhance assessment of
      effects of community-based exercise interventions aimed at improving muscle
      strength. OBJECTIVE: The aim of this study was to investigate the use of troponin
      as a newly proposed biomarker of skeletal muscle health when determining the
      outcomes of strength-training programs designed for community-dwelling adults
      over the age of 65 years. METHODS: Outcomes of two strength training programs
      ("Peer Exercise Program Promotes Independence" and "Stay Strong, Stay Healthy")
      were assessed using physical performance tests designed for senior fitness
      evaluation, grip strength, and changes in serum levels of skeletal muscle
      specific troponin T (sTnT). RESULTS: Improvement in physical performance,
      including a significant increase in grip strength, was associated with a
      significant reduction in serum levels of sTnT. DISCUSSION: Findings from these
      studies suggest that, when "Peer Exercise Program Promotes Independence" and
      "Stay Strong, Stay Healthy" are implemented for at least 10 weeks, significant
      gains in strength are achieved. This strength improvement was associated with a
      reduction in serum levels of troponin, supporting the use of troponin as a novel
      biomarker of muscle health in the assessment of strength training programs for
      the older adults. Reduced sTnT after exercise intervention suggests that skeletal
      muscles become stronger and less susceptible to damage because of the exercise
      regimens.

PMID- 24589645
TI  - Fatigue in the presence of coronary heart disease.
AB  - BACKGROUND: Fatigue is a prevalent and disabling symptom associated with many
      acute and chronic conditions, including acute myocardial infarction and chronic
      heart failure. Fatigue has not been explored in patients with stable coronary
      heart disease (CHD). OBJECTIVES: The purpose of this partially mixed sequential
      dominant status study was to (a) describe fatigue in patients with stable CHD;
      (b) determine if specific demographic (gender, age, education, income),
      physiological (hypertension, hyperlipidemia), or psychological (depressive
      symptoms) variables were correlated with fatigue; and (c) determine if fatigue
      was associated with health-related quality of life. The theory of unpleasant
      symptoms was used as a conceptual framework. METHODS: Patients (N = 102)
      attending two cardiology clinics completed the Fatigue Symptom Inventory, Patient
      Health Questionnaire-9, and Medical Outcomes Study Short Form-36 to measure
      fatigue, depressive symptoms, and health-related quality of life. Thirteen
      patients whose interference from fatigue was low, moderate, or high participated
      in qualitative interviews. RESULTS: Forty percent of the sample reported fatigue
      more than 3 days of the week lasting more than one half of the day. Lower
      interference from fatigue was reported on standardized measures compared with
      qualitative interviews. Compared with men, women reported a higher fatigue
      intensity (p = .003) and more interference from fatigue (p = .007). In regression
      analyses, depressive symptoms were the sole predictor of fatigue intensity and
      interference. DISCUSSION: Patients with stable CHD reported clinically relevant
      levels of fatigue. Patients with stable CHD may discount fatigue as they adapt to
      their symptoms. Relying solely on standardized measures may provide an incomplete
      picture of fatigue burden in patients with stable CHD.

PMID- 24589646
TI  - Factors associated with toileting disability in older adults without dementia
      living in residential care facilities.
AB  - BACKGROUND: Older adults without dementia living in residential care facilities
      with toileting disability have increased care costs and dependency. Understanding
      associated factors could guide prevention and management strategies. OBJECTIVE:
      The aim of this study was to identify the prevalence of and factors associated
      with toileting disability in this population. METHODS: This was a cross-sectional
      analysis of the 2010 National Survey of Residential Care Facilities. A subsample
      (n = 2,395) of adults aged 65 years or older, without dementia, and with the
      potential to implement behavioral interventions was examined. Associated factors
      were classified according to the disablement process as pathologies, impairments,
      functional limitations, coexisting disabilities, and intraindividual and
      extraindividual factors. Logistic regression models accounting for the stratified
      two-stage probability sampling design were used to identify factors associated
      with toileting disability. RESULTS: Residents were mostly White women, aged 85
      years and older. Prevalence of toileting disability was 15%. Associated factors
      included reporting fair or poor health; living in a facility with four or less
      residents; living in a for-profit facility; having bowel incontinence, urinary
      incontinence, more physical impairments, and visual and hearing impairments; and
      needing assistance with bathing, dressing, and transferring. DISCUSSION:
      Multicomponent and multidisciplinary prevention and management efforts should be
      designed for residents without dementia. Future studies testing the efficacy of
      prevention efforts are needed and should include treatments for incontinence;
      physical activity programs targeting impairments with walking, standing, sitting,
      stooping, reaching, and grasping; and therapy to improve dressing, bathing, and
      transferring skills.

PMID- 24589647
TI  - Validation and psychometric properties of the neonatal intensive care unit
      parental beliefs scale.
AB  - BACKGROUND: Parental perception of their infants and confidence/beliefs about
      their parenting are among the most salient factors influencing outcomes of
      preterm infants. OBJECTIVES: The purpose of this study was to assess the
      psychometric properties of scores on the Neonatal Intensive Care Unit Parental
      Beliefs Scale (NICU PBS) in a sample of mothers and fathers of preterm infants
      receiving intensive care. The NICU PBS is a rating instrument designed to assess
      parental beliefs about their premature infant and their role during
      hospitalization. METHODS: The sample consisted of 245 mothers and 143 fathers. As
      part of the Creating Opportunities for Parent Empowerment trial, participants
      completed the NICU PBS 4-8 days after NICU admission and again approximately 4
      days before discharge. Validation data were obtained at various times throughout
      the study. Confirmatory factor analysis was used to evaluate the NICU PBS factor
      structure. RESULTS: A three-factor solution was accepted (Parental Role
      Confidence, Parent-Baby Interaction, and Knowledge of the NICU). Reliability of
      scores on the total scale and subscales was high; Cronbach's alpha ranged from
      .75 to .91. Test-retest correlations ranged from .84 to .92. Younger maternal
      age; birth of another child; return to work within the past 12 months; and lower
      stress, depression, and anxiety were all significantly associated with higher
      scores on all subscales and the total score. Lower education, lower household
      income, receipt of Medicaid, and non-White race were associated with higher
      scores on the parent role confidence subscale and total. Lower household income
      and receipt of Medicaid were associated with higher Parent-Baby Interaction
      scores. DISCUSSION: The NICU PBS can be used reliably with mothers and fathers of
      premature infants who are hospitalized in the NICU, and it may be a useful scale
      in predicting parental stress, depression, and anxiety.

PMID- 24589649
TI  - Blog text about female incontinence: presentation of self, disclosure, and social
      risk assessment.
AB  - BACKGROUND: Female urinary incontinence is a significant health concern that
      often remains undisclosed to healthcare providers, often because of embarrassment
      and fear of a negative response. OBJECTIVES: The purpose of this study was to
      explore communication patterns found in blog text regarding self-presentation by
      women living with incontinence for clues to facilitate disclosure. METHODS: This
      is a descriptive, empirical study of publically archived blog text (years
      inclusive 2006-2011; N = 16,629 words from 19 bloggers) by women communicating
      about urinary incontinence, utilizing methods of content analysis. RESULTS:
      Valence and word concordance analysis showed that words indicative of
      facilitating social connections were used more often in proximity with close
      contacts (Z = -2.68, p = .004) and words indicative of blocking social
      connections were used more often in proximity with community contacts (Z = -2.97,
      p = .002). Differences between descriptions of facilitative and blocking
      reactions from healthcare providers were not significant (Z = -0.28, p = .39).
      Cluster analysis indicated a decreasing level of negatively charged descriptors
      of incontinence-related communications as the context moved from the hidden self
      to close contacts and then to the public sphere. Word frequency analysis
      identified a pattern in the blog text about urinary incontinence of self
      presenting as otherwise fit, healthy, and competent. DISCUSSION: Study results
      suggest that any report of incontinence concerns, including joking or casual
      references, should be addressed because women may not disclose the degree to
      which symptoms affect their psychosocial health. Further research is needed to
      explore whether providers might facilitate disclosure of urinary incontinence by
      first acknowledging the woman's strengths, thereby creating a sense of safety and
      acceptance.

PMID- 24589648
TI  - Sleep in persons with frontotemporal dementia and their family caregivers.
AB  - BACKGROUND: Dementia is associated with disruptions in sleep and sleep quality
      for patients and their family caregivers. Little is known about the impact of
      frontotemporal dementia (FTD) on sleep. OBJECTIVE: The purpose of this study was
      to characterize sleep in patients with FTD and their family caregivers. METHODS:
      Twenty-two patient-caregiver dyads were enrolled: Thirteen behavioral variant FTD
      (bvFTD) and nine semantic dementia (SD). Sleep and sleep quality data were
      collected for 2 weeks using diaries and Actiwatches. RESULTS: Patients with bvFTD
      and SD spent more time in bed at night compared to their caregivers. Nighttime
      behaviors were reported more frequently by caregivers for the bvFTD patients and
      strongly correlated with caregiver distress. Actigraphy data showed normal sleep
      efficiency and timing of the nighttime sleep period for both patients and their
      caregivers. Caregivers of patients with bvFTD reported poorer sleep quality
      compared to the SD caregivers. A greater number of bvFTD caregivers compared to
      SD reported negative aspects of sleep quality for themselves and used sleep
      medications more frequently. CONCLUSION: The clinical manifestations of bvFTD
      appear to be associated with different and more distressing impacts on the
      caregiver sleep quality than SD.

PMID- 24589650
TI  - Fear of hypoglycemia in women and men with type 1 diabetes.
AB  - BACKGROUND: Severe hypoglycemia is a serious complication of type1 diabetes
      feared by many who have the disease. OBJECTIVES: The aim of this study was to
      investigate specific fears related to hypoglycemia in adults with type 1 diabetes
      and to investigate how aspects of fear of hypoglycemia may differ between
      genders. METHODS: A cross-sectional study with questionnaires sent to 636
      patients with type 1 diabetes, aged 18-75 years, who attended the outpatient
      clinic at St. Olavs Hospital, Trondheim, Norway. Fears related to hypoglycemia
      were assessed using the Hypoglycemia Fear Survey II Worry subscale (HFS-II
      Worry). RESULTS: The response rate was 70% (N = 445, 216 women and 229 men). The
      mean HFS-II-Worry score was higher in women than in men (2.46 [SD = 0.80] vs.
      2.22 [SD = 0.74], respectively; p < .001). Women scored higher than men in all
      items in the HFS-II-Worry, and women's average scores were statistically
      significantly higher in 5 of the 18 items after correction for multiple
      comparisons. The largest gender differences in mean scores occurred in the items
      "low blood glucose interfering with important things," "becoming upset and
      difficult," "difficulty thinking clearly," and "feeling lightheaded or dizzy." In
      both women and men, the highest mean scores appeared in the worry items "become
      hypoglycemic while sleeping" and "not having food available." DISCUSSION: In this
      sample of Norwegian adults with type 1 diabetes, women expressed more concerns
      about hypoglycemia than men. The highest HFS-II-Worry scores occurred in the same
      items in women and men, but the largest gender differences in mean scores
      appeared across a variety of other items, some of which were related to social
      esteem.

PMID- 24589653
TI  - 68Ga chelating bioorthogonal tetrazine polymers for the multistep labeling of
      cancer biomarkers.
AB  - We have developed a (68)Ga metal chelating bioorthogonal tetrazine dextran probe
      that is highly reactive with trans-cyclooctene modified monoclonal antibodies for
      multistep imaging applications. Confocal microscopy and positron emission
      tomography (PET) were used to characterize the dextran probe in vitro and in
      vivo. 

PMID- 24589655
TI  - The nature of the structural phase transition from the hexagonal (4H) phase to
      the cubic (3C) phase of silver.
AB  - The phase transition from the hexagonal 4H polytype of silver to the commonly
      known 3C (fcc) phase was studied in detail using x-ray diffraction, electron
      microscopy, differential scanning calorimetry and Raman spectroscopy. The phase
      transition is irreversible and accompanied by extensive microstructural changes
      and grain growth. Detailed scanning and isothermal calorimetric analysis suggests
      that it is an autocatalytic transformation. Though the calorimetric data suggest
      an exothermic first-order phase transition with an onset at 155.6  degrees C (for
      a heating rate of 2 K min(-1)) and a latent heat of 312.9 J g(-1), the
      microstructure and the electrical resistance appear to change gradually from much
      lower temperatures. The 4H phase shows a Raman active mode at 64.3 cm(-1) (at 4
      K) that undergoes mode softening as the 4H -> 3C transformation temperature is
      approached. A first-principles density functional theory calculation shows that
      the stacking fault energy of 4H-Ag increases monotonically with temperature. That
      4H-Ag has a higher density of stacking faults than 3C-Ag, implies the
      metastability of the former at higher temperatures. Energetically, the 4H phase
      is intermediate between the hexagonal 2H phase and the 3C ground state, as
      indicated by the spontaneous transformation of the 2H to the 4H phase at -4 
      degrees C. Our data appear to indicate that the 4H-Ag phase is stabilized at
      reduced dimensions and thermally induced grain growth is probably responsible for
      triggering the irreversible transformation to cubic Ag. 

PMID- 24589656
TI  - Bayesian uncertainty assessment of a semi-distributed integrated catchment model
      of phosphorus transport.
AB  - Process-based models of nutrient transport are often used as tools for management
      of eutrophic waters, as decision makers need to judge the potential effects of
      alternative remediation measures, under current conditions and with future land
      use and climate change. All modelling exercises entail uncertainty arising from
      various sources, such as the input data, selection of parameter values and the
      choice of model itself. Here we perform Bayesian uncertainty assessment of an
      integrated catchment model of phosphorus (INCA-P). We use an auto-calibration
      procedure and an algorithm for including parametric uncertainty to simulate
      phosphorus transport in a Norwegian lowland river basin. Two future scenarios
      were defined to exemplify the importance of parametric uncertainty in generating
      predictions. While a worst case scenario yielded a robust prediction of increased
      loading of phosphorus, a best case scenario only gave rise to a reduction in load
      with probability 0.78, highlighting the importance of taking parametric
      uncertainty into account in process-based catchment scale modelling of possible
      remediation scenarios. Estimates of uncertainty can be included in information
      provided to decision makers, thus making a stronger scientific basis for sound
      decisions to manage water resources. 

PMID- 24589654
TI  - Preliminary data on growth and enzymatic abilities of soil fungus Humicolopsis
      cephalosporioides at different incubation temperatures.
AB  - BACKGROUND: Nothofagus pumilio (Poepp & Endl.) Krasser, known as "lenga" is the
      most important timber wood species in southernmost Patagonia (Argentina).
      Humicolopsis cephalosporioides Cabral & Marchand is a soil fungus associated with
      Nothofagus pumilio forests, which has outstanding cellulolytic activity. However,
      there is no information about the ability of this fungus to use organic
      substrates other than cellulose, and its ability to produce different enzyme
      systems, as well as its response to temperature. AIMS: The aim of this study was
      to examine the role of H. cephalosporioides in degradation processes in N.
      pumilio forests in detail by evaluating the in vitro ability of four isolates of
      this fungus to grow and produce different lytic enzyme systems, and their
      response to incubation temperature. METHODS: The ability of the fungi to grow and
      produce enzyme systems was estimated by inoculating them on agar media with
      specific substrates, and the cultures were incubated at three temperatures.
      RESULTS: A differential behavior of each strain in levels of growth and enzyme
      activity was found according to the medium type and/or incubation temperature.
      CONCLUSIONS: A intra-specific variability was found in H. cephalosporioides.
      Likewise a possible link between the saprotrophic role of this fungus in N.
      pumilio forests and the degradation of organic matter under stress conditions,
      such as those from frosty environments, was also discussed.

PMID- 24589652
TI  - The translation elongation factor eEF2 is a novel tumor-associated antigen
      overexpressed in various types of cancers.
AB  - Recent studies have shown that cancer immunotherapy could be a promising
      therapeutic approach for the treatment of cancer. In the present study, to
      identify novel tumor-associated antigens (TAAs), the proteins expressed in a
      panel of cancer cells were serologically screened by immunoblot analysis and the
      eukaryotic elongation factor 2 (eEF2) was identified as an antigen that was
      recognized by IgG autoantibody in sera from a group of patients with head and
      neck squamous cell carcinoma (HNSCC) or colon cancer. Enzyme-linked immunosorbent
      assay showed that serum eEF2 IgG Ab levels were significantly higher in
      colorectal and gastric cancer patients compared to healthy individuals.
      Immunohistochemistry experiments showed that the eEF2 protein was overexpressed
      in the majority of lung, esophageal, pancreatic, breast and prostate cancers,
      HNSCC, glioblastoma multiforme and non-Hodgkin's lymphoma (NHL). Knockdown of
      eEF2 by short hairpin RNA (shRNA) significantly inhibited the growth in four eEF2
      expressing cell lines, PC14 lung cancer, PCI6 pancreatic cancer, HT1080
      fibrosarcoma and A172 glioblastoma cells, but not in eEF2-undetectable MCF7
      cells. Furthermore, eEF2-derived 9-mer peptides, EF786 (eEF2 786-794 aa) and
      EF292 (eEF2 292-300 aa), elicited cytotoxic T lymphocyte (CTL) responses in
      peripheral blood mononuclear cells (PBMCs) from an HLA-A*24:02- and an HLA
      A*02:01-positive healthy donor, respectively, in an HLA-A-restricted manner.
      These results indicated that the eEF2 gene is overexpressed in the majority of
      several types of cancers and plays an oncogenic role in cancer cell growth.
      Moreover, the eEF2 gene product is immunogenic and a promising target molecule of
      cancer immunotherapy for several types of cancers.

PMID- 24589657
TI  - Proximal FAD histidine residue influences interflavin electron transfer in
      cytochrome P450 reductase and methionine synthase reductase.
AB  - Cytochrome P450 reductase (CPR) and methionine synthase reductase (MSR) transfer
      reducing equivalents from NADPH to FAD to FMN. In CPR, hydride transfer and
      interflavin electron transfer are kinetically coupled steps, but in MSR the two
      catalytic steps are represented by two distinct kinetic phases leading to
      transient formation of the FAD hydroquinone. In human CPR, His(322) forms a
      hydrogen-bond with the highly conserved Asp(677), a member of the catalytic
      triad. The catalytic triad is present in MSR, but Ala(312) replaces the histidine
      residue. To examine if this structural variation accounts for differences in
      their kinetic behavior, reciprocal substitutions were created. Substitution of
      His(322) for Ala in CPR does not affect the rate of NADPH hydride transfer or the
      FAD redox potentials, but does impede interflavin electron transfer. For MSR,
      swapping Ala(312) for a histidine residue resulted in the kinetic coupling of
      hydride and interflavin electron transfer, and eliminated the formation of the
      FAD hydroquinone intermediate. For both enzymes, placement of the His residue in
      the active site weakens coenzyme binding affinity. The data suggest that the
      proximal FAD histidine residue accelerates proton-coupled electron transfer from
      FADH2 to the higher potential FMN; a mechanism for this catalytic role is
      discussed. 

PMID- 24589658
TI  - Kinetic control in the CID-induced elimination of H3PO4 from phosphorylated
      serine probed using IRMPD spectroscopy.
AB  - InfraRed Multiple Photon Dissociation (IRMPD) spectroscopy was used to assay the
      structural features of the fragment ions resulting from the elimination of H3PO4
      in the Collision-Induced Dissociation (CID) of protonated serine. The results are
      interpreted with the aid of density functional theory calculations. Experiment
      and theory point to an aziridine-ring structure, implying participation of the
      vicinal amino group in the formation of this species. This finding constitutes a
      benchmark for investigating the same process in the CID of phosphorylated
      peptides. 

PMID- 24589661
TI  - Psychiatrist vilified by UK newspapers is cleared of all charges.

PMID- 24589660
TI  - Patient-oriented and performance-based outcomes after knee autologous chondrocyte
      implantation: a timeline for the first year of recovery.
AB  - CONTEXT: It is well established that autologous chondrocyte implantation (ACI)
      can require extended recovery postoperatively; however, little information exists
      to provide clinicians and patients with a timeline for anticipated function
      during the first year after ACI. OBJECTIVE: To document the recovery of
      functional performance of activities of daily living after ACI. PATIENTS: ACI
      patients (n = 48, 29 male; 35.1 +/- 8.0 y). INTERVENTION: All patients completed
      functional tests (weight-bearing squat, walk-across, sit-to-stand, step-up/over,
      and forward lunge) using the NeuroCom long force plate (Clackamas, OR) and
      completed patient-reported outcome measures (International Knee Documentation
      Committee Subjective Knee Evaluation Form, Lysholm, Western Ontario and McMaster
      Osteoarthritis Index [WOMAC], and 36-Item Short-Form Health Survey)
      preoperatively and 3, 6, and 12 mo postoperatively. MAIN OUTCOME MEASURES: A
      covariance pattern model was used to compare performance and self-reported
      outcome across time and provide a timeline for functional recovery after ACI.
      RESULTS: Participants demonstrated significant improvement in walk-across stride
      length from baseline (42.0% +/- 8.9% height) at 6 (46.8% +/- 8.1%) and 12 mo
      (46.6% +/- 7.6%). Weight bearing on the involved limb during squatting at 30
      degrees , 60 degrees , and 90 degrees  was significantly less at 3 mo than
      presurgery. Step-up/over time was significantly slower at 3 mo (1.67 +/- 0.69 s)
      than at baseline (1.49 +/- 0.33 s), 6 mo (1.51 +/- 0.36 s), and 12 mo (1.40 +/-
      0.26 s). Step-up/over lift-up index was increased from baseline (41.0% +/- 11.3%
      body weight [BW]) at 3 (45.0% +/- 11.7% BW), 6 (47.0% +/- 11.3% BW), and 12 mo
      (47.3% +/- 11.6% BW). Forward-lunge time was decreased at 3 mo (1.51 +/- 0.44 s)
      compared with baseline (1.39 +/- 0.43 s), 6 mo (1.32 +/- 0.05 s), and 12 mo (1.27
      +/- 0.06). Similarly, forward-lunge impact force was decreased at 3 mo (22.2% +/-
      1.4% BW) compared with baseline (25.4% +/- 1.5% BW). The WOMAC demonstrated
      significant improvements at 3 mo. All patient-reported outcomes were improved
      from baseline at 6 and 12 mo postsurgery. CONCLUSIONS: Patients' perceptions of
      improvements may outpace physical changes in function. Decreased function for at
      least the first 3 mo after ACI should be anticipated, and improvement in
      performance of tasks requiring weight-bearing knee flexion, such as squatting,
      going down stairs, or lunging, may not occur for a year or more after surgery.

PMID- 24589662
TI  - Modelling the yeast interactome.
AB  - The topology behind biological interaction networks has been studied for over a
      decade. Yet, there is no definite agreement on the theoretical models which best
      describe protein-protein interaction (PPI) networks. Such models are critical to
      quantifying the significance of any empirical observation regarding those
      networks. Here, we perform a comprehensive analysis of yeast PPI networks in
      order to gain insights into their topology and its dependency on interaction
      screening technology. We find that: (1) interaction-detection technology has
      little effect on the topology of PPI networks; (2) topology of these interaction
      networks differs in organisms with different cellular complexity (human and
      yeast); (3) clear topological difference is present between PPI networks, their
      functional sub-modules, and their inter-functional "linkers"; (4) high confidence
      PPI networks have more "geometrical" topology compared to predicted, incomplete,
      or noisy PPI networks; and (5) inter-functional "linker" proteins serve as
      mediators in signal transduction, transport, regulation and organisational
      cellular processes. 

PMID- 24589663
TI  - Bovine and porcine fibroblasts can be immortalized with intact karyotype by the
      expression of mutant cyclin dependent kinase 4, cyclin D, and telomerase.
AB  - Cattle and pigs comprise the most economically important livestock. Despite their
      importance, cultured cells from these species, which are useful for physiological
      analyses, are quite limited in cell banks. One of the reasons for the limited
      number of cell lines is the difficulty in their establishment. To overcome
      limitations in cell-line establishment, we attempted to immortalize bovine and
      porcine fibroblasts by transduction of multiple cell cycle regulators (mutant
      cyclin dependent kinase 4, cyclin D and telomerase reverse transcriptase). The
      transduced cells continued to display a stable proliferation rate and did not
      show cellular senescence. Furthermore, cell cycle assays showed that induction of
      these exogenous genes enhanced turnover of the cell cycle, especially at the G1-S
      phase. Furthermore, our established cell lines maintained normal diploid
      karyotypes at 98-100%. Our study demonstrated that bypassing p16/Rb-mediated cell
      arrest and activation of telomerase activity enabled efficient establishment of
      immortalized bovine- and porcine-derived fibroblasts. The high efficiency of
      establishing cell lines suggests that the networks of cell cycle regulators,
      especially p16/Rb-associated cell cycle arrest, have been conserved during
      evolution of humans, cattle, and pigs. 

PMID- 24589664
TI  - MAGI: Methylation analysis using genome information.
AB  - By incorporating annotation information into the analysis of next-generation
      sequencing DNA methylation data, we provide an improvement in performance over
      current testing procedures. Methylation analysis using genome information (MAGI)
      is applicable for both unreplicated and replicated data, and provides an
      effective analysis for studies with low sequencing depth. When compared with
      current tests, the annotation-informed tests provide an increase in statistical
      power and offer a significance-based interpretation of differential methylation. 

PMID- 24589665
TI  - A general quantitative pH sensor developed with dicyandiamide N-doped high
      quantum yield graphene quantum dots.
AB  - A general quantitative pH sensor for environmental and intracellular applications
      was developed by the facile hydrothermal preparation of dicyandiamide (DCD) N
      doped high quantum yield (QY) graphene quantum dots (GQDs) using citric acid (CA)
      as the carbon source. The obtained N-doped GQDs have excellent photoluminesence
      (PL) properties with a relatively high QY of 36.5%, suggesting that N-doped
      chemistry could promote the QY of carbon nanomaterials. The possible mechanism
      for the formation of the GQDs involves the CA self-assembling into a nanosheet
      structure through intermolecular H-bonding at the initial stage of the reaction,
      and then the pure graphene core with many function groups formed through the
      dehydration between the carboxyl and hydroxyl of the intermolecules under
      hydrothermal conditions. These N-doped GQDs have low toxicity, and are
      photostable and pH-sensitive between 1.81 to 8.96, giving a general pH sensor
      with a wide range of applications from real water to intracellular contents. 

PMID- 24589666
TI  - Chronic constipation, irritable bowel syndrome with constipation and constipation
      with pain/discomfort: similarities and differences.
AB  - OBJECTIVES: Some patients with chronic constipation (CC) have abdominal pain and
      discomfort (painful CC) without fulfilling the criteria for irritable bowel
      syndrome (IBS). Our aim was to investigate similarities and differences among
      nonpainful CC, painful CC, and CC in patients with IBS according to prevalence,
      individual symptoms, associated factors, and impact on health-related quality of
      life and use of medical resources. METHODS: We conducted a telephone survey of a
      random sample of the Spanish population (N=1500). Bowel symptoms were recorded
      using the Rome III questionnaire, health-related quality of life using the short
      form-12 (SF-12) and quality of live in constipation-20 (CVE-20) questionnaires,
      and self-reported constipation, lifestyle habits, and consultation behavior using
      an ad hoc questionnaire. RESULTS: The overall prevalence of CC was 19.2%, with
      prevalence by subgroups being 13.9% for nonpainful CC, 2.0% for painful CC, and
      3.3% for CC in patients with IBS. CC was more prevalent among women at a ratio of
      2.7:1. Subjects with painful CC and CC in patients with IBS were younger,
      reported more constipation, and had more symptoms than subjects with nonpainful
      CC. Age and physical activity were significantly associated with CC. Symptoms
      associated with consultation were abdominal pain and digitation. Nonpainful CC
      patients were more satisfied with laxative use than were the other subgroups.
      Subjects with CC showed a significant impairment in the physical and mental
      component of the SF-12 questionnaire. CONCLUSIONS: CC appears to be a spectrum;
      most patients do not have abdominal pain/discomfort but others (with otherwise
      quite similar characteristics) are patients with IBS or are out of any
      established diagnosis.

PMID- 24589667
TI  - Irritable bowel syndrome in middle-aged and elderly Palestinians: its prevalence
      and effect of location of residence.
AB  - OBJECTIVES: The prevalence of irritable bowel syndrome (IBS) around the world is
      variable, ranging from as little as 1.1 to 45%. Limited studies have been carried
      out in Arab populations. The aim of this study was to determine the prevalence of
      IBS and its subtypes in the West Bank, Palestine, and to assess variation by
      locality of residence. METHODS: We conducted a population-based, cross-sectional
      study. Participants were randomly selected from all districts of the West Bank,
      including cities, villages, and refugee camps, and they were at least 50 years of
      age. Participants completed the Rome III IBS questionnaire along with demographic
      data. The primary outcome was the effect of location of residence on the
      prevalence of IBS. A multivariable logistic regression model was used to assess
      the difference in IBS prevalence based on locality of residence. RESULTS: A total
      of 1,601 people were approached for interview, of which 1,352 agreed to
      participate (response rate 84%). Most participants (53%; n=637) lived in urban
      centers. The overall prevalence of IBS was 30% (28-33%). IBS was more common in
      refugee camps (34%) and in villages (34%) compared with urban centers (27%)
      (P<0.05). Mixed IBS (IBS-M) was the most common of IBS subtypes (55%, n=244). In
      a multivariable logistic regression analysis, living in refugee camps (odds ratio
      (OR) 1.68 (95% confidence interval (CI) 1.14-2.40), P=0.005) and in villages (OR
      1.33 (1.02-1.72), P=0.033) was associated with increased odds of having IBS when
      compared with residents of urban centers. IBS, IBS with constipation, and IBS-M
      were more common in women than in men (P<0.05). CONCLUSIONS: The prevalence of
      IBS among middle-aged and elderly residents of Palestine is high. Residents in
      refugee camps and rural areas have a higher incidence of IBS than those in urban
      areas.

PMID- 24589668
TI  - Symptoms and endoscopic features at barrett's esophagus diagnosis: implications
      for neoplastic progression risk.
AB  - OBJECTIVES: Risk stratification of Barrett's esophagus (BE) patients based on
      clinical and endoscopic features may help to optimize surveillance practice for
      esophageal adenocarcinoma (EAC) development. The aim of this study was to
      investigate patient symptoms and endoscopic features at index endoscopy and risk
      of neoplastic progression in a large population-based cohort of BE patients.
      METHODS: A retrospective review of hospital records relating to incident BE
      diagnosis was conducted in a subset of patients with specialized intestinal
      metaplasia from the Northern Ireland BE register. Patients were matched to the
      Northern Ireland Cancer Registry to identify progressors to EAC or esophageal
      high-grade dysplasia (HGD). Cox proportional hazards models were applied to
      evaluate the association between endoscopic features, symptoms, and neoplastic
      progression risk. RESULTS: During 27,997 person-years of follow-up, 128 of 3,148
      BE patients progressed to develop HGD/EAC. Ulceration within the Barrett's
      segment, but not elsewhere in the esophagus, was associated with an increased
      risk of progression (hazard ratio (HR) 1.72; 95% confidence interval (CI): 1.08
      2.76). Long-segment BE carried a significant sevenfold increased risk of
      progression compared with short-segment BE; none of the latter group developed
      EAC during the study period. Conversely, the absence of reflux symptoms was
      associated with an increased risk of cancer progression (HR 1.61; 95% CI: 1.05
      2.46). CONCLUSIONS: BE patients presenting with a long-segment BE or Barrett's
      ulcer have an increased risk of progressing to HGD/EAC and should be considered
      for more intense surveillance. The absence of reflux symptoms at BE diagnosis is
      not associated with a reduced risk of malignant progression, and may carry an
      increased risk of progression.

PMID- 24589669
TI  - Abnormal structure and function of the esophagogastric junction and proximal
      stomach in gastroesophageal reflux disease.
AB  - OBJECTIVES: This study applies concurrent magnetic resonance imaging (MRI) and
      high-resolution manometry (HRM) to test the hypothesis that structural factors
      involved in reflux protection, in particular, the acute insertion angle of the
      esophagus into the stomach, are impaired in gastroesophageal reflux disease
      (GERD) patients. METHODS: A total of 24 healthy volunteers and 24 patients with
      mild-moderate GERD ingested a test meal. Three-dimensional models of the
      esophagogastric junction (EGJ) were reconstructed from MRI images. Measurements
      of the esophagogastric insertion angle, gastric orientation, and volume change
      were obtained. Esophageal function was assessed by HRM. Number of reflux events
      and EGJ opening during reflux events were assessed by HRM and cine-MRI.
      Statistical analysis applied mixed-effects modeling. RESULTS: The esophagogastric
      insertion angle was wider in GERD patients than in healthy subjects (+7 degrees 
      +/- 3 degrees ; P=0.03). EGJ opening during reflux events was greater in GERD
      patients than in healthy subjects (19.3 mm vs. 16.8 mm; P=0.04). The position of
      insertion and gastric orientation within the abdomen were also altered (both
      P<0.05). Median number of reflux events was 3 (95% CI: 2.5-4.6) in GERD and 2
      (95% CI: 1.8-3.3) in healthy subjects (P=0.09). Lower esophageal sphincter (LES)
      pressure was lower (-11 +/- 2 mm Hg; P<0.0001) and intra-abdominal LES length was
      shorter (-1.0 +/- 0.3 cm, P<0.0006) in GERD patients. CONCLUSIONS: GERD patients
      have a wider esophagogastric insertion angle and have altered gastric morphology;
      structural changes that could compromise reflux protection by the "flap valve"
      mechanism. In addition, the EGJ opens wider during reflux in GERD patients than
      in healthy volunteers: an effect that facilitates volume reflux of gastric
      contents.

PMID- 24589670
TI  - The problem of Helicobacter pylori resistance to antibiotics: a systematic review
      in Latin America.
AB  - OBJECTIVES: Latin America has a high prevalence of Helicobacter pylori infection
      and associated diseases, including gastric cancer. Antibiotic therapy can
      eradicate the bacterial infection and decrease associated morbidity and
      mortality. To tailor recommendations for optimal treatments, we summarized
      published literature and calculated region- and country-specific prevalences of
      antibiotic resistance. METHODS: Searches of PubMed and regional databases for
      observational studies evaluating H. pylori antibiotic resistance yielded a total
      of 59 independent studies (56 in adults, 2 in children, and 1 in both groups)
      published up to October 2013 regarding H. pylori isolates collected between 1988
      and 2011. Study-specific prevalences of primary resistance to commonly prescribed
      antibiotics were summarized using random-effects models. Between-study
      heterogeneity was assessed by meta-regression. As a sensitivity analysis, we
      extended our research to studies of patients with prior H. pylori-eradication
      therapy. RESULTS: Summary prevalences of antimicrobial primary resistance among
      adults varied by antibiotic, including 12% for clarithromycin (n=35 studies), 53%
      for metronidazole (n=34), 4% for amoxicillin (n=28), 6% for tetracycline (n=20),
      3% for furazolidone (n=6), 15% for fluoroquinolones (n=5), and 8% for dual
      clarithromycin and metronidazole (n=10). Resistance prevalence varied
      significantly by country, but not by year of sample collection. Analyses
      including studies of patients with prior therapy yielded similar estimates.
      Pediatric reports were too few to be summarized by meta-analysis. CONCLUSIONS:
      Resistance to first-line anti-H. pylori antibiotics is high in Latin American
      populations. In some countries, the empirical use of clarithromycin without
      susceptibility testing may not be appropriate. These findings stress the need for
      appropriate surveillance programs, improved antimicrobial regulations, and
      increased public awareness.

PMID- 24589671
TI  - Hyponatremia and sodium picosulfate bowel preparations in older adults.
AB  - OBJECTIVES: Bowel preparations are commonly prescribed drugs. Case reports and
      our clinical experience suggest that sodium picosulfate bowel preparations can
      precipitate severe hyponatremia in some older adults. At present, this risk is
      poorly quantified. We investigated the association between sodium picosulfate use
      and the risk of hyponatremia in older adults. METHODS: We conducted a population
      based retrospective cohort study using six linked administrative databases in
      Ontario, Canada. All Ontario residents over the age of 65 years who filled an
      outpatient bowel preparation prescription before colonoscopy were eligible. We
      enrolled new users of either sodium picosulfate (n=99,237) or polyethylene glycol
      (n=48,595). The primary outcome was hospitalization with hyponatremia within 30
      days of the bowel preparation assessed by database codes. The secondary outcomes
      were hospitalization with urgent head computed tomography (CT) (a proxy for acute
      central nervous system disturbance) and all-cause mortality. RESULTS: The
      baseline characteristics of the two groups, including patient demographics,
      comorbid conditions, and concomitant medications, were nearly identical. Compared
      with polyethylene glycol, sodium picosulfate was associated with a higher risk of
      hospitalization with hyponatremia (absolute risk increase: 0.05%, 95% confidence
      interval (CI): 0.04-0.06%, relative risk (RR): 2.4, 95% CI: 1.5-3.9), but not
      hospitalization with urgent CT head (RR: 1.1, 95% CI: 0.7-1.4) or mortality (RR:
      0.9, 95% CI: 0.7-1.3). CONCLUSIONS: Sodium picosulfate bowel preparations lead to
      more hyponatremia than polyethylene glycol. There was no evidence of increased
      risk of acute neurologic symptoms or mortality. The absolute increase in risk of
      hospitalization with hyponatremia remains low but may be avoidable through
      appropriate fluid intake or preferential use of polyethylene glycol in some older
      adults.

PMID- 24589672
TI  - Bidirectional relationships between sleep duration and screen time in early
      childhood.
AB  - IMPORTANCE: Sleep duration and media use (ie, computer use and television
      viewing) have important implications for the health and well-being of children.
      Population data suggest that shorter sleep duration and excessive screen time are
      growing problems among children and could be interacting issues. OBJECTIVE: To
      examine whether bidirectional relationships exist between sleep duration and
      media use among children, and whether these associations are moderated by child-
      and household-related factors. DESIGN, SETTING, AND PARTICIPANTS: Cohort study of
      a representative sample of 3427 Australian children (4-5 years of age at baseline
      [51.2%male children]), obtained from the Longitudinal Study of Australian
      Children. Data were available from 3 waves (2004, 2006, and 2008) when children
      were 4, 6, and 8 years of age, respectively. MAIN OUTCOMES AND MEASURES: Sleep
      duration and media use. RESULTS Bidirectional relationships were observed between
      sleep duration and media use; for instance, total media use at 4 years of age was
      significantly associated with sleep duration at 6 years of age (a = .0.06 [95%CI,
      .0.10 to .0.02]), with media use at 6 years of age predicting sleep duration at 8
      years of age (a = .0.06 [95%CI, .0.11 to .0.02]). Sleep duration at 4 years of
      age was associated with media use at 6 years of age (a = .0.10 [95%CI, .0.14 to
      .0.05]), with sleep duration at 6 years of age predicting media use at 8 years of
      age (a = .0.08 [95%CI, .0.13 to .0.03]). Several of these bidirectional
      relationships varied by socioeconomic status. CONCLUSIONS AND RELEVANCE: The
      results supported the hypotheses that bidirectional relationships exist between
      sleep duration and media use among children. These findings are important given
      recent population trends for increased media use and shorter sleep durations
      among children.

PMID- 24589673
TI  - Utility of ultrasound in the ICU.
AB  - PURPOSE OF REVIEW: Use of ultrasound in the acute care setting has become more
      common in recent years. However, it still remains underutilized in the
      perioperative management of critical patients. In this review, we aim to increase
      the awareness of ultrasound as an important diagnostic modality that can be used
      in the perioperative period to improve patient care. Our main focus will be in
      describing the diagnostic uses of ultrasound to identify cardiac, pulmonary,
      airway and vascular diseases commonly encountered in acute care settings. RECENT
      FINDINGS: We find that ultrasound can be used in a quick fashion to assess a
      haemodynamically unstable patient. Protocols are available to use ultrasound as a
      part of cardiopulmonary resuscitation. Ultrasound can help in deciding fluid vs.
      pressor treatment by evaluating the inferior vena cava and other cardiac
      structures.Lung ultrasound can not only help in diagnosing pneumothoracies and
      effusions but also look at lung recruitment and diaphragmatic movement, hence can
      aid in deciding extubation strategies. This modality can be utilized for
      confirmation of endotracheal tube.Recent interest in axillary vein cannulation
      with ultrasound guidance has gained some momentum. SUMMARY: This article covers
      the recent developments and literature available on point of care ultrasound and
      its utilization in the perioperative period. We have not covered some other
      important uses of ultrasound such as abdominal examination looking at the aorta
      and other abdominal organs. This was beyond the scope of this article.

PMID- 24589676
TI  - The coherent potential approximation for strongly correlated systems: electronic
      structure and magnetic properties of NiO-ZnO solid solutions.
AB  - A method of electronic structure calculations for strongly correlated disordered
      materials is developed employing the basic idea of the coherent potential
      approximation. The evolution of the electronic structure and spin magnetic moment
      value with the concentration x in strongly correlated Ni1-xZnxO solid solutions
      is investigated in the framework of this method. The values of the energy gap and
      magnetic moment obtained are in agreement with the available experimental data. 

PMID- 24589677
TI  - Galectin-1-mediated cell adhesion, invasion and cell death in human anaplastic
      large cell lymphoma: regulatory roles of cell surface glycans.
AB  - Galectin-1 is known to be one of the extracellular matrix proteins. To elucidate
      the biological roles of galectin-1 in cell adhesion and invasion of human
      anaplastic large cell lymphoma, we performed cell adhesion and invasion assays
      using the anaplastic large cell lymphoma cell line H-ALCL, which was previously
      established in our laboratory. From the cell surface lectin array, treatment with
      neuraminidase from Arthrobacter ureafaciens which cleaves all linkage types of
      cell surface sialic acid enhanced Arachis hypogaea (PNA), Helix pomatia (HPA) and
      Phaseolus vulgaris-L (L-PHA) lectin binding reactivity to cell surface of
      lymphoma cells suggesting that neuraminidase removes cell surface sialic acid. In
      cell adhesion and invasion assays treatment with neuraminidase markedly enhanced
      cell adhesion to galectin-1 and decreased cell invasive capacity through galectin
      1. alpha2,6-linked sialic acid may be involved in masking the effect of the
      interaction between galectin-1 and cell surface glycans. H-ALCL cells expressed
      the beta-galactoside-alpha2,6-sialyltransferase ST6Gal1. On resialylation assay
      by recombinant ST6Gal1 with CMP-Neu5Ac, alpha2,6-resialylation of L-PHA reactive
      oligosaccharide by ST6Gal1 resulted in inhibition of H-ALCL cell adhesion to
      galectin-1 compared to the desialylated H-ALCL cells. On knockdown experiments,
      knockdown of ST6Gal1 dramatically enhanced cell adhesion to galectin-1. N
      glycosylation inhibitor swainsonine treatment resulted in enhancement of cell
      adhesion to galectin-1. In glycomic analysis using the lectin blocking assay
      treatment with PNA, Artocarpus integrifolia (Jacalin), Glycine max (SBA), Helix
      pomatia (HPA), Vicia villosa (VVA), Ulex europaeus (UEA-1), Triticum vulgaris
      (WGA), Canavalia ensiformis (ConA), Phaseolus vulgaris-L (L-PHA), Phaseolus
      vulgaris-E4 (E-PHA), Datura stramonium (DSA) lectins resulted in modulation of
      lymphoma cell to galectin-1 suggesting that several types of glycans may regulate
      cell adhesion to galectin-1 by steric hindrance. The adhesive capacity of H-ALCL
      cells is regulated by phosphatidylinositol 3 phosphate kinase (PI3K) and actin
      cytoskeleton, and the invasive capacity of H-ALCL cells is regulated by PI3K,
      mitogen-activated protein kinase (MAPK), Rho and actin cytoskeleton. Furthermore,
      galectin-1-induced cell death in H-ALCL cells was accompanied by inhibition of
      CD45 protein tyrosine phosphatase (PTP) activity. In conclusion, cell adhesion
      and invasion to galectin-1 appeared to be regulated by cell surface sialylation
      and N-glycosylation, and galectin-1 regulates cell death through inhibition of
      CD45 PTP activity of H-ALCL.

PMID- 24589679
TI  - Removal of Mn from aqueous solution using fly ash and its hydrothermal synthetic
      zeolite.
AB  - A number of water purification processes have been developed in recent years
      based on the utilisation of low-cost materials with high pollutant removal
      efficiency. Among these materials, fly ash and zeolite synthesised from fly ash
      are two examples of high-efficiency adsorbents. Column absorption tests were
      performed in order to compare the manganese sorption behaviour of an Italian coal
      fly ash and zeolite synthesised from it. Different masses of both materials (10
      60 g) were exposed to solutions containing a total metal concentration of 10
      mg/L. Batch adsorption studies were also conducted to determine the effect of
      time on the removal on Mn sequestration. The results indicate that both materials
      are effective for the removal of Mn from aqueous solution by precipitation due to
      the high pH of the solid/liquid mixtures. However, the leaching tests reveal that
      the amount of Mn removed from the fly ash was greater than that leached from the
      zeolite, thereby indicating that the metal is partially sequestrated by zeolite. 

PMID- 24589680
TI  - Pneumomediastinum in patients with AIDS: a case report and literature review.
AB  - OBJECTIVE: Pneumomediastinum is a rare complication of opportunistic infections
      in HIV-infected patients. However, the relationship between the causative
      pathogens and the prognosis is unclear. We report the case of a patient with AIDS
      presenting with community-acquired pneumonia complicated by pneumomediastinum.
      The cases of a further 10 HIV-infected patients with pneumomediastinum reported
      in the English language literature are reviewed. METHODS: PubMed was searched for
      cases of HIV-infected patients with pneumomediastinum published in the English
      language literature. RESULTS: Pneumocystis jirovecii is the most common pathogen
      causing pneumonia and concurrent pneumomediastinum in HIV-infected patients. Only
      one of the identified cases was caused by cytomegalovirus. Excluding the two
      cases with incomplete information, the overall mortality rate in the remaining
      nine cases was 55.5%. CONCLUSION: In HIV-infected patients, Pneumocystis
      jirovecii pneumonia can occasionally present as pneumomediastinum. In such cases,
      adequate appropriate antimicrobial therapy is needed due to the high mortality
      rate.

PMID- 24589681
TI  - Fulminant atypical Cryptococcus neoformans pneumonia confirmed by PLEX-ID.
AB  - Use of the PLEX-ID system can lead to a rapid molecular diagnosis in
      microbiology. To illustrate the clinical implications of this new diagnostic
      tool, we present the case of a 46-year-old patient admitted with severe
      respiratory failure and septic shock. Cryptococcal pneumonia was diagnosed by
      Fungi-FluorTM staining of the bronchoalveolar lavage (BAL) and the patient tested
      positive for HIV. Unfortunately, he died 12h after admission despite intensive
      care support and treatment with broad-spectrum antibiotics, amphotericin B, and
      flucytosine. Retrospective use of the PLEX-ID on the BAL, bronchial aspirate, and
      blood yielded Cryptococcus neoformans in all fluids tested. Rapid molecular
      diagnosis with PLEX-ID, especially when performed on the blood of septic
      patients, may reduce the time to adequate treatment and limit the number of
      diagnostic procedures needed. 

PMID- 24589682
TI  - A response to "infections associated with religious rituals", by James Pellerin
      and Michael B. Edmond.

PMID- 24589683
TI  - The benefits of exercise in progressive MS: some cautious optimism.

PMID- 24589684
TI  - To look for a needle in a haystack: the search for autoantibodies in multiple
      sclerosis.
AB  - The search for autoantibodies in multiple sclerosis (MS) has been challenging for
      the last 3 decades. With the development of new proteomic methods and advances in
      expression and assay technologies, progress in the identification of MS
      autoantibodies has been made. A number of MS-specific autoantibodies have been
      proposed, most of them targeting proteins expressed in oligodendrocytes and along
      the myelin sheath. In this review, we summarize the status of antibody research
      in MS and then discuss recent developments and future strategies in defining and
      characterizing the potential antigenic targets of autoantibodies in MS. 

PMID- 24589685
TI  - MRI measures should be a primary outcome endpoint in Phase III randomized,
      controlled trials in multiple sclerosis: yes.

PMID- 24589686
TI  - MRI measures should be a primary outcome endpoint in phase III randomized
      controlled trials in multiple sclerosis: no.

PMID- 24589687
TI  - MRI measures should be a primary outcome endpoint in phase III randomised
      controlled trials in multiple sclerosis: commentary.

PMID- 24589688
TI  - New features of the cell wall of the radio-resistant bacterium Deinococcus
      radiodurans.
AB  - We have analyzed the cell wall of the radio-resistant bacterium Deinococcus
      radiodurans. Unexpectedly, the bacterial envelope appears to be organized in
      different complexes of high molecular weight. Each complex is composed of several
      proteins, most of which are coded by genes of unknown function and the majority
      are constituents of the inner/outer membrane system. One of the most abundant
      complexes is constituted by the gene DR_0774. This protein is a type of secretin
      which is a known subunit of the homo-oligomeric channel that represents the main
      bulk of the type IV piliation family. Finally, a minor component of the pink
      envelope consists of several inner-membrane proteins. The implications of these
      findings are discussed. 

PMID- 24589689
TI  - Surviving sepsis: a review of the latest guidelines.

PMID- 24589690
TI  - Nursing2014 survey results: wound care and prevention.

PMID- 24589691
TI  - Bioactive attributes of tomatoes possessing dg, ogc, and rin genes.
AB  - We present the results of the first study characterizing new tomato hybrids,
      possessing dark green (dg), old gold crimson (og(c)), and ripening inhibitor
      (rin) genes, that determines the bioactive molecules and in vitro antioxidant
      potential of the peel and pulp of the fruits. The hybrids developed from Berika
      and BCT-115 (having the dg gene) were superior to those developed from BCT-119
      and BCT-111 (carrying og(c) and rin genes, respectively), in relation to their
      nutritional potential. A wide range (mg/100 g FW) of ascorbic acid (~21-40),
      lycopene (~2-4), beta-carotene (~0.5-1.7), total flavonoids (~4.6-20.0), and
      total phenols (~16-30) was recorded in the pulp. The peel fraction of the
      tomatoes was identified as an important reservoir of antioxidant bioactive
      compounds viz. lycopene (~8-25), beta-carotene (~1.6-3.1), total flavonoids (~42
      82), and total phenols (~59-83). The radical scavenging activity ranged from ~45
      78 and 21-50% in the peel and pulp, respectively, whereas the metal chelating
      activity was found to range from ~23-42 and ~15-26% in peel and pulp,
      respectively, among all the hybrids. This finding offers a new direction towards
      the development of new tomato hybrids that possess not only a good shelf life,
      but also a nutritional status as well. Moreover, utilizing tomato peel as a
      source of phytochemicals could offer diverse opportunities for nutraceutical and
      functional food applications.

PMID- 24589692
TI  - On-field signs and symptoms associated with recovery duration after concussion in
      high school and college athletes: a critically appraised topic.
AB  - CLINICAL SCENARIO: Over the past decade, sport-related concussions have received
      increased attention due to their frequency and severity over a wide range of
      athletics. Clinicians have developed return-to-play protocols to better manage
      concussions in young athletes; however, a standardized process projecting the
      length of recovery time after concussion has remained an elusive piece of the
      puzzle. The recovery times associated with such an injury once diagnosed can last
      anywhere from 1 wk to several months. Risk factors that could lead to protracted
      recovery times include a history of 1 or multiple concussions and a greater
      number, severity, and duration of symptoms after the injury. Examining the
      possible relationship between on-field or sideline signs and symptoms and
      recovery times would give clinicians the confident ability to properly treat and
      manage an athlete's recovery process in a more systematic manner. Furthermore,
      identifying factors after a head injury that may be predictive of protracted
      recovery times would be useful for athletes, parents, and coaches alike. FOCUSED
      CLINICAL QUESTION: Which on-field and sideline signs and symptoms affect length
      of recovery after concussion in high school and college athletes?

PMID- 24589693
TI  - Abnormal lithium isotope composition from the ancient lithospheric mantle beneath
      the North China Craton.
AB  - Lithium elemental and isotopic compositions of olivines in peridotite xenoliths
      from Hebi in the North China Craton provide direct evidence for the highly
      variable delta(7)Li in Archean lithospheric mantle. The delta(7)Li in the cores
      of olivines from the Hebi high-Mg# peridotites (Fo > 91) show extreme variation
      from -27 to +21, in marked deviation from the delta(7)Li range of fresh MORB
      (+1.6 to +5.6) although the Li abundances of the olivines are within the range of
      normal mantle (1-2 ppm). The Li abundances and delta(7)Li characteristics of the
      Hebi olivines could not have been produced by recent diffusive-driven isotopic
      fractionation of Li and therefore the delta(7)Li in the cores of these olivines
      record the isotopic signature of the subcontinental lithospheric mantle. Our data
      demonstrate that abnormal delta(7)Li may be preserved in the ancient lithospheric
      mantle as observed in our study from the central North China Craton, which
      suggest that the subcontinental lithospheric mantle has experienced modification
      of fluid/melt derived from recycled oceanic crust. 

PMID- 24589694
TI  - A celebration of failure.

PMID- 24589695
TI  - Lomitapide and mipomersen: two first-in-class drugs for reducing low-density
      lipoprotein cholesterol in patients with homozygous familial
      hypercholesterolemia.

PMID- 24589696
TI  - Right versus left ventricular failure: differences, similarities, and
      interactions.

PMID- 24589698
TI  - Massive air embolism after lung biopsy.

PMID- 24589699
TI  - A nervous heart.

PMID- 24589700
TI  - Cardiology patient page: device interventions for stroke prevention in atrial
      fibrillation.

PMID- 24589702
TI  - Letter by Maier et al regarding article, "Emergency department bypass for ST
      segment-elevation myocardial infarction patients identified with a prehospital
      electrocardiogram: a report from the American Heart Association Mission: Lifeline
      Program".

PMID- 24589703
TI  - Response to letter regarding article, "Emergency department bypass for ST-segment
      elevation myocardial infarction patients identified with a prehospital
      electrocardiogram: a report from the American Heart Association Mission: Lifeline
      Program".

PMID- 24589704
TI  - Folded Cr12Co12 and Cr12Ni12 wheels: a sharp increase in nuclearity of
      heterometallic chromium rings.
AB  - Two novel record-sized heterometallic Cr12M12 (M = Co, Ni) chromium wheels with
      an unusual saddle-like architecture are created by reacting appropriate precursor
      complexes with the bridging ligand 2,2'-bipyrimidine. 

PMID- 24589705
TI  - Pleiotropic functions of TIMP-1 in patients with chronic kidney disease.

PMID- 24589706
TI  - Human immunodeficiency virus type 1 Vpr increases hepatitis C virus RNA
      replication in cell culture.
AB  - Human immunodeficiency virus (HIV) coinfection with hepatitis C virus (HCV) is
      associated with an increased HCV RNA level, as well as a more rapid progression
      to cirrhosis and end-stage liver disease. However, the mechanism underlying this
      effect is largely unknown. Here, we investigated the role of HIV-1 Vpr in HCV
      infection and clearly demonstrated that Vpr increased the replication of both the
      infectious HCV full-length genome and the subgenomic replicon. We also
      demonstrated that Vpr increased HCV infection by enhancing RNA replication but
      not viral entry or translation. Further, we showed that Vpr could partially
      overcome the anti-HCV effect of PEG-IFN. Our findings not only partially explain
      the clinical observation that patients coinfected with HIV and HCV have higher
      levels of HCV RNA and viral load than HCV mono-infected patients but also provide
      important information for HCV treatment in HIV/HCV coinfected patients. 

PMID- 24589707
TI  - Newcastle disease virus: current status and our understanding.
AB  - Newcastle disease (ND) is one of the highly pathogenic viral diseases of avian
      species. ND is economically significant because of the huge mortality and
      morbidity associated with it. The disease is endemic in many third world
      countries where agriculture serves as the primary source of national income.
      Newcastle disease virus (NDV) belongs to the family Paramyxoviridae and is well
      characterized member among the avian paramyxovirus serotypes. In recent years,
      NDV has lured the virologists not only because of its pathogenic potential, but
      also for its oncolytic activity and its use as a vaccine vector for both humans
      and animals. The NDV based recombinant vaccine offers a pertinent choice for the
      construction of live attenuated vaccine due to its modular nature of
      transcription, minimum recombination frequency, and lack of DNA phase during
      replication. Our current understanding about the NDV biology is expanding rapidly
      because of the availability of modern molecular biology tools and high-throughput
      complete genome sequencing. 

PMID- 24589709
TI  - Ubiquilin 2: a component of the ubiquitin-proteasome system with an emerging role
      in neurodegeneration.
AB  - Ubiquilin 2, which is encoded by the UBQLN2 gene, plays a critical role in
      protein clearance pathways including the ubiquitin-proteasome system and
      autophagy. Ubiquilin 2 physically associates with ubiquitin ligases and
      proteasomes to mediate protein degradation. It also plays a role in the
      regulation of cell signalling and cell cycle progression, and association with
      cytoskeletal elements. Recent studies have revealed that ubiquilin 2 also plays a
      pathogenic role in neurodegenerative disease, including amyotrophic lateral
      sclerosis (ALS), and ALS-frontotemporal dementia (ALS-FTD). Rare UBQLN2 mutations
      cause a small subset of ALS and ALS-FTD cases. More widespread is the presence of
      ubiquilin 2 positive inclusions in the affected neurons of some familial and
      sporadic ALS and ALS-FTD patients. These discoveries have led to the hypothesis
      that perturbation in protein clearance, mediated by ubiquilin 2, is an important
      pathogenic mechanism in neurodegeneration. 

PMID- 24589710
TI  - Molecular cobalt electrocatalyst for proton reduction at low overpotential.
AB  - Linear trimetallic Co(III)/Co(II)/Co(III) cobalt complexes with bridging acyl
      alkoxy ligands are electrocatalysts for the reduction of tosic acid in
      acetonitrile. The -OCMe2CH2COMe complex appears to operate homogeneously, and at
      a modest onset overpotential of 175 mV. A turnover frequency of ca. 80 s(-1) was
      observed at an overpotential of 300 mV. 

PMID- 24589711
TI  - Bone's dark side: mutated osteoblasts implicated in leukemia.
AB  - Bone-lining osteolineage cells were previously implicated as contributors to
      hematological disorders and malignancies. A recent report in Nature now
      demonstrates that a specific mutation in mouse collagen-expressing osteoblastic
      cells leads to MDS and AML with 100% penetrance and is associated with strikingly
      similar findings in human patients. 

PMID- 24589712
TI  - Gold nanoparticle wires for sensing DNA and DNA/protein interactions.
AB  - The discontinuous Vertical Evaporation-driven Colloidal Deposition (dVECD) method
      has been used as a green technique for formatting nanoparticle wires by the
      direct deposition of nanoparticles from colloid suspensions onto hydrophilic
      substrates, without any lithographic procedures. Gold nanoparticles of different
      sizes are deposited into wire arrays for electronic detection of biological
      molecules. A sensitive detection of DNA molecules as low as ~1 pM is achieved due
      to a high surface to volume ratio of the porous structures. The effects of the
      gold nanoparticles' size, DNA concentration, and DNA length on detection
      sensitivity of these gold nanoparticle wire sensors are discussed. Moreover, we
      can also detect the interaction between DNAs and proteins. Gold nanoparticle
      wires prepared by the nontoxic and simple dVECD are promising for detecting
      viruses involved in diseases. 

PMID- 24589715
TI  - Anemia in chronic kidney disease treating the numbers, not the patients.

PMID- 24589716
TI  - Metastable electron-pair states in a two-dimensional crystal.
AB  - We study possible quantum states of two correlated electrons in a two-dimensional
      periodic potential and find a metastable energy band of electron pairs between
      the two lowest single-electron bands. These metastable states result from
      interplay of the electron-electron Coulomb interaction and the strength of the
      crystal potential. The paired electrons are bound in the same unit cell in
      relative coordinates with an average distance between them of approximately one
      third of the crystal period. Furthermore, we discuss how such electron pairs can
      possibly be stabilized in a many-electron system. 

PMID- 24589714
TI  - The de novo DNA methyltransferase DNMT3A in development and cancer.
AB  - DNA methylation, one of the best-characterized epigenetic modifications, plays
      essential roles in development, aging and diseases. The de novo DNA
      methyltransferase DNMT3A is responsible for the establishment of de novo genomic
      DNA methylation patterns and, as such, involved in normal development as well as
      in many diseases including cancer. In recent years, our understanding of this
      important protein has made significant progress, which was facilitated by
      stunning development in the analysis of the DNA methylome of multiple organs and
      cell types. In this review, recent developments in the characterization of DNMT3A
      were discussed with special emphasis on the roles of DNMT3A in development and
      cancer. 

PMID- 24589718
TI  - Ischaemic conditioning strategies for the nephrologist: a promise lost in
      translation?
AB  - Over the last quarter of a century, a huge effort has been made to develop
      interventions that can minimise ischaemia reperfusion injury. The most potent of
      these are the ischaemic conditioning strategies, which comprise ischaemic
      preconditioning, remote ischaemic preconditioning and ischaemic postconditioning.
      While much of the focus for these interventions has been on protecting the
      myocardium, other organs including the kidney can be similarly protected.
      However, translation of these beneficial effects from animal models into routine
      clinical practice has been less straightforward than expected. In this review, we
      examine the role of ischaemic conditioning strategies in reducing tissue injury
      from the 'bench to the bedside' and discuss the barriers to their greater
      translation. 

PMID- 24589719
TI  - Reactive oxygen species in diabetic nephropathy: friend or foe?
AB  - Based on the numerous cellular and animal studies over the last decades, it has
      been postulated that reactive oxygen species (ROS) are important secondary
      messengers for signalling pathways associated with apoptosis, proliferation,
      damage and inflammation. Their adverse effects were considered to play a leading
      role in the onset and progression of type 1 and type 2 diabetes mellitus as well
      as in the complication of diabetic disease leading to vascular-, cardiac-, neuro
      degeneration, diabetic retinopathy and diabetic nephropathy. All these
      complications were mostly linked to the generation of the superoxide anion, due
      to a prolonged hyperglycaemia in diabetes, and this anion was almost 'blamed for
      everything', despite the fact that its measurement and detection in life systems
      is extremely complicated due to the short lifespan of the superoxide anion.
      Therefore, a tremendous amount of research has been focused on finding ways to
      suppress ROS production. However, a recent report from Dugan et al. shed new
      insights into the life detection of superoxide generation in diabetes and raised
      the question of whether we treat the diabetes-related complications correctly or
      the target is somewhat different as thought. This review will focus on some
      aspects of this novel concept for the role of ROS in diabetic nephropathy. 

PMID- 24589720
TI  - Impact of liver fibrosis staging in hepatitis C virus (HCV) patients with kidney
      failure.

PMID- 24589721
TI  - Focal segmental glomerulosclerosis: towards a better understanding for the
      practicing nephrologist.
AB  - Focal and segmental glomerulosclerosis (FSGS) is a common histopathological
      lesion that can represent a primary podocytopathy, or occur as an adaptive
      phenomenon consequent to nephron mass reduction, a scar from a healing vasculitic
      lesion, direct drug toxicity or viral infection among other secondary causes.
      Thus, the presence of an FSGS lesion in a renal biopsy does not confer a disease
      diagnosis, but rather represents the beginning of an exploratory process,
      hopefully leading ultimately to identification of a specific etiology and its
      appropriate treatment. We define primary FSGS as a 'primary' podocytopathy
      characterized clinically by the presence of nephrotic syndrome in a patient with
      an FSGS lesion on light microscopy and widespread foot process effacement on
      electron microscopy (EM). Secondary FSGS is commonly characterized by the absence
      of nephrotic syndrome and the presence of segmental foot process effacement on
      EM. Failure to accurately differentiate between the primary and secondary forms
      of FSGS has resulted in many patients undergoing unnecessary immunosuppressive
      treatment. Here, we review some key points that may assist the practicing
      nephrologist to distinguish between primary and secondary FSGS. 

PMID- 24589717
TI  - Antibody engineering and therapeutics, The Annual Meeting of the Antibody
      Society: December 8-12, 2013, Huntington Beach, CA.
AB  - The 24th Antibody Engineering & Therapeutics meeting brought together a broad
      range of participants who were updated on the latest advances in antibody
      research and development. Organized by IBC Life Sciences, the gathering is the
      annual meeting of The Antibody Society, which serves as the scientific sponsor.
      Preconference workshops on 3D modeling and delineation of clonal lineages were
      featured, and the conference included sessions on a wide variety of topics
      relevant to researchers, including systems biology; antibody deep sequencing and
      repertoires; the effects of antibody gene variation and usage on antibody
      response; directed evolution; knowledge-based design; antibodies in a complex
      environment; polyreactive antibodies and polyspecificity; the interface between
      antibody therapy and cellular immunity in cancer; antibodies in cardiometabolic
      medicine; antibody pharmacokinetics, distribution and off-target toxicity;
      optimizing antibody formats for immunotherapy; polyclonals, oligoclonals and
      bispecifics; antibody discovery platforms; and antibody-drug conjugates.

PMID- 24589722
TI  - Metabolic abnormalities in autosomal dominant polycystic kidney disease.
AB  - Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited
      kidney disorder and is known to affect all ethnic groups with a prevalence of
      1:400-1:1000 live births. The kidney in ADKPD is characterized by the formation
      of numerous cysts which progressively expand and eventually destroy normal kidney
      structure and function. Cysts occur in other organs outside the kidney, most
      commonly in the liver, pancreas and spleen. Important non-cystic features include
      intracranial aneurysms and cardiac valve defects. Less well recognized are a
      range of metabolic abnormalities, which could be involved in cystic disease
      progression or be associated with other disease complications. In this review, we
      summarize the literature suggesting that metabolic abnormalities could be
      important under-recognised and under-treated features in ADPKD. 

PMID- 24589723
TI  - Interaction between systemic inflammation and renal tubular epithelial cells.
AB  - Systemic inflammation is known to target tubular epithelial cells (TECs), leading
      to acute kidney injury. Tubular cells have been implicated in the response to
      inflammatory mediators in ischaemic and septic renal damage. Moreover, loss of
      tubular cells by apoptosis or epithelial-to-mesenchymal transition may ingenerate
      conditions that lead to progression towards chronic kidney disease. On the other
      hand, TECs may actively contribute to the production of inflammatory mediators
      that may propagate the injury locally or in distant organs. In the present
      review, we discuss the tubular cell response and its contribution to systemic
      inflammation. 

PMID- 24589725
TI  - Effects of an HIV-Care-Program on immunological parameters in HIV-positive
      patients in Yaounde, Cameroon: a cluster-randomized trial.
AB  - OBJECTIVES: To measure the effects of an HIV-Care-Program, focusing on nutrition
      and lifestyle, which can be provided at scale to HIV-infected patients, on
      clinical and anthropometrical parameters, and health status. METHODS: A cluster
      randomized trial, including 5 health facilities randomized to intervention n =
      100 (HIV-Care-Program) or control n = 101 (Usual-Care). The HIV-Care-Program
      consisted of counseling lessons for 6 months, on: nutrition, hygiene, coping with
      stigma and discrimination, embedded in practical activities. Outcome variables
      were CD4 count after 6 months and time to antiretroviral therapy (ARV)
      initiation, using analysis of covariance and Kaplan-Meier method, respectively.
      RESULTS: After 6 months, CD4 count dropped by 46.3 cells (7.7%) (intervention)
      and 129 (23%) (control) (p = 0.003). Mean time to ARV; 5.9 months 95% CI (5.9,
      6.0) (intervention); 4.9 months 95% CI (4.7, 5.2) (control) (p < 0.004). There
      was a partial correlation between CD4 count and initial viral load (r = -0.190, p
      = 0.017). CONCLUSIONS: The intervention provides a low-cost alternative improving
      health status, slowing down CD4 cell decline, delaying initiation of ARV and thus
      freeing local ARV capacities for patients in urgent need.

PMID- 24589726
TI  - Fibromyalgia in patients with other rheumatic diseases: prevalence and
      relationship with disease activity.
AB  - Fibromyalgia (FM) is a syndrome characterized by chronic widespread pain and the
      presence of specific tender points. The prevalence of FM has been estimated at 2
      7 % of the general global population. The presence of FM in several rheumatic
      diseases with a structural pathology has been reported as 11-30 %. The objectives
      of this study were to determine the prevalence of FM and to evaluate the possible
      relationship between FM existence and disease activity among rheumatic diseases.
      The study group included 835 patients--197 rheumatoid arthritis (RA), 67 systemic
      lupus erythematosus (SLE), 119 ankylosing spondylitis (AS), 238 osteoarthritis
      (OA), 14 familial Mediterranean fever (FMF), 53 Behcet's disease (BD), 71 gout,
      25 Sjogren's syndrome (SS), 20 vasculitis, 29 polymyalgia rheumatica (PMR), and
      two polymyositis (PM)--with or without FM. Recorded information included age,
      gender, laboratory parameters, presence of fatigue, and disease activity indexes.
      The prevalence of FM in patients with rheumatologic diseases was found to be 6.6
      % for RA, 13.4 % for SLE, 12.6 % for AS, 10.1 % for OA, 5.7 % for BD, 7.1 % for
      FMF, 12 % for SS, 25 % for vasculitis, 1.4 % for gout, and 6.9 % for PMR. One out
      of two patients with PM was diagnosed with FM. Some rheumatologic cases (AS, OA)
      with FM were observed mostly in female patients (p = 0.000). Also, there were
      significant correlations between disease activity indexes and Fibromyalgia Impact
      Questionnaire scores for most rheumatologic patients (RA, AS, OA, and BD) (p <
      0.05; respectively, r = 0.6, 0.95, 0.887, and 1). Concomitant FM is a common
      clinical problem in rheumatologic diseases, and its recognition is important for
      the optimal management of these diseases. Increased pain, physical limitations,
      and fatigue may be interpreted as increased activity of these diseases, and a
      common treatment option is the prescription of higher doses of biologic agents or
      corticosteroids. Considerations of the FM component in the management of
      rheumatologic diseases increase the likelihood of the success of the treatment.

PMID- 24589728
TI  - Racemization of aspartic acid in root dentin as a tool for age estimation in a
      Kuwaiti population.
AB  - Estimation of age is one of the most significant tasks in forensic practice.
      Amino acid racemization is considered one of the most reliable and accurate
      methods of age estimation and aspartic acid shows a high racemization reaction
      rate. The present study has investigated the application of aspartic acid
      racemization in age estimation in a Kuwaiti population using root dentin from a
      total of 89 upper first premolar teeth. The D/L ratio of aspartic acid was
      obtained by HPLC technique in a test group of 50 subjects and a linear regression
      line was established between aspartic acid racemization and age. The correlation
      coefficient (r) was 0.97, and the standard error of estimation was +/-1.26 years.
      The racemization age "t" of each subject was calculated by applying the following
      formula: ln [(1 + D/L)/(1 - D/L)] = 0.003181 t + (-0.01591). When the proposed
      formula "estimated age t = ln [(1 + D/L)/(1 - D/L)] + 0.01591/0.003181" was
      applied to a validation group of 39 subjects, the range of error was less than
      one year in 82.1% of the cases and the standard error of estimation was +/-1.12.
      The current work has established a reasonably significant correlation of the D-/L
      aspartic acid ratio with age, and proposed an apparently reliable formula for
      calculating the age in Kuwaiti populations through aspartic acid racemization.
      Further research is required to find out whether similar findings are applicable
      to other ethnic populations. 

PMID- 24589724
TI  - Multicentre prospective validation of a urinary peptidome-based classifier for
      the diagnosis of type 2 diabetic nephropathy.
AB  - BACKGROUND: Diabetic nephropathy (DN) is one of the major late complications of
      diabetes. Treatment aimed at slowing down the progression of DN is available but
      methods for early and definitive detection of DN progression are currently
      lacking. The 'Proteomic prediction and Renin angiotensin aldosterone system
      Inhibition prevention Of early diabetic nephRopathy In TYpe 2 diabetic patients
      with normoalbuminuria trial' (PRIORITY) aims to evaluate the early detection of
      DN in patients with type 2 diabetes (T2D) using a urinary proteome-based
      classifier (CKD273). METHODS: In this ancillary study of the recently initiated
      PRIORITY trial we aimed to validate for the first time the CKD273 classifier in a
      multicentre (9 different institutions providing samples from 165 T2D patients)
      prospective setting. In addition we also investigated the influence of sample
      containers, age and gender on the CKD273 classifier. RESULTS: We observed a high
      consistency of the CKD273 classification scores across the different centres with
      areas under the curves ranging from 0.95 to 1.00. The classifier was independent
      of age (range tested 16-89 years) and gender. Furthermore, the use of different
      urine storage containers did not affect the classification scores. Analysis of
      the distribution of the individual peptides of the classifier over the nine
      different centres showed that fragments of blood-derived and extracellular matrix
      proteins were the most consistently found. CONCLUSION: We provide for the first
      time validation of this urinary proteome-based classifier in a multicentre
      prospective setting and show the suitability of the CKD273 classifier to be used
      in the PRIORITY trial.

PMID- 24589730
TI  - Sox11 promotes endogenous neurogenesis and locomotor recovery in mice spinal cord
      injury.
AB  - We introduced a lentiviral vector containing the Sox11 gene into injured spinal
      cords of mice to evaluate the therapeutic potential of Sox11 in spinal cord
      injury. Sox11 markedly improved locomotor recovery after spinal cord injury and
      this recovery was accompanied by an up-regulation of Nestin/Doublecortin
      expression in the injured spinal cord. Sox11 was mainly located in endogenous
      neural stem cells lining the central canal and in newly-generated neurons in the
      spinal cord. In addition, Sox 11 significantly induced expressions of BDNF in the
      spinal cords of LV-Sox11-treated mice. We concluded that Sox11 induced activation
      of endogenous neural stem cells into neuronal determination and migration within
      the injured spinal cord. The resultant increase of BDNF at the injured site might
      form a distinct neurogenic niche which induces a final neuronal differentiation
      of these neural stem cells. Enhancing Sox11 expression to induce neurogenic
      differentiation of endogenous neural stem cells after injury may be a promising
      strategy in restorative therapy after SCI in mammals. 

PMID- 24589727
TI  - Application of vitamin E to antagonize SWCNTs-induced exacerbation of allergic
      asthma.
AB  - The aggravating effects of zero-dimensional, particle-shaped nanomaterials on
      allergic asthma have been previously investigated, but similar possible effects
      of one-dimensional shaped nanomaterials have not been reported. More importantly,
      there are no available means to counteract the adverse nanomaterial effects to
      allow for their safe use. In this study, an ovalbumin (OVA)-sensitized rat asthma
      model was established to investigate whether single walled carbon nanotubes
      (SWCNTs) aggravate allergic asthma. The results showed that SWCNTs in rats
      exacerbated OVA-induced allergic asthma and that this exacerbation was
      counteracted by concurrent administration vitamin E. A mechanism involving the
      elimination of reactive oxygen species, downregulation of Th2 responses, reduced
      Ig production, and the relief of allergic asthma symptoms was proposed to explain
      the antagonistic effects of vitamin E. This work could provide a universal
      strategy to effectively protect people with allergic asthma from SWCNTs or
      similar nanomaterial-induced aggravating effects. 

PMID- 24589731
TI  - Cell cycle-dependent regulation of Aurora kinase B mRNA by the Microprocessor
      complex.
AB  - Aurora kinase B regulates the segregation of chromosomes and the spindle
      checkpoint during mitosis. In this study, we showed that the Microprocessor
      complex, which is responsible for the processing of the primary transcripts
      during the generation of microRNAs, destabilizes the mRNA of Aurora kinase B in
      human cells. The Microprocessor-mediated cleavage kept Aurora kinase B at a low
      level and prevented premature entrance into mitosis. The cleavage was reduced
      during mitosis leading to the accumulation of Aurora kinase B mRNA and protein.
      In addition to Aurora kinase B mRNA, the processing of other primary transcripts
      of miRNAs were also decreased during mitosis. We found that the cleavage was
      dependent on an RNA helicase, DDX5, and the association of DDX5 and DDX17 with
      the Microprocessor was reduced during mitosis. Thus, we propose a novel mechanism
      by which the Microprocessor complex regulates stability of Aurora kinase B mRNA
      and cell cycle progression. 

PMID- 24589732
TI  - 7-Ketocholesterol as marker of cholesterol oxidation in model and food systems:
      when and how.
AB  - Cholesterol can undergo oxidation through enzymatic or chemical mechanisms,
      generating a wide range of oxidation products (COPs) with adverse biological
      effects. COPs are characterized by different functional groups and are produced
      in different ratios or amounts, depending on the treatment and storage
      conditions. To follow the cholesterol oxidation process, 7-ketocholesterol (7-KC)
      has been often used as an oxidation marker in both model and food systems, since
      it is easily formed and is one of the most representative ring COPs. However, 7
      KC does not always rise with increasing time/temperature conditions, especially
      in complex systems and high-protein or extensively processed foods. The following
      review provides a critical picture of the utilization of 7-KC as a cholesterol
      oxidation marker in model and food systems, focusing on the possible causes and
      effects of the different behaviours and trends, as well as on the advantages and
      disadvantages of using 7-KC when the extent of cholesterol oxidation is to be
      assessed. 

PMID- 24589733
TI  - TALE nickase mediates high efficient targeted transgene integration at the human
      multi-copy ribosomal DNA locus.
AB  - Although targeted gene addition could be stimulated strikingly by a DNA double
      strand break (DSB) created by either zinc finger nucleases (ZFNs) or TALE
      nucleases (TALENs), the DSBs are really mutagenic and toxic to human cells. As a
      compromised solution, DNA single-strand break (SSB) or nick has been reported to
      mediate high efficient gene addition but with marked reduction of random
      mutagenesis. We previously demonstrated effective targeted gene addition at the
      human multicopy ribosomal DNA (rDNA) locus, a genomic safe harbor for the
      transgene with therapeutic potential. To improve the transgene integration
      efficiency by using TALENs while lowering the cytotoxicity of DSBs, we created
      both TALENs and TALE nickases (TALENickases) targeting this multicopy locus. A
      targeting vector which could integrate a GFP cassette at the rDNA locus was
      constructed and co-transfected with TALENs or TALENickases. Although the fraction
      of GFP positive cells using TALENs was greater than that using TALENickases
      during the first few days after transfection, it reduced to a level less than
      that using TALENickases after continuous culture. Our findings showed that the
      TALENickases were more effective than their TALEN counterparts at the multi-copy
      rDNA locus, though earlier studies using ZFNs and ZFNickases targeting the single
      copy loci showed the reverse. Besides, TALENickases mediated the targeted
      integration of a 5.4 kb fragment at a frequency of up to 0.62% in HT1080 cells
      after drug selection, suggesting their potential application in targeted gene
      modification not being limited at the rDNA locus.

PMID- 24589734
TI  - Differences in c-Jun N-terminal kinase recognition and phosphorylation of closely
      related stathmin-family members.
AB  - The stathmin (STMN) family of tubulin-binding phosphoproteins are critical
      regulators of interphase microtubule dynamics and organization in a broad range
      of cellular processes. c-Jun N-terminal kinase (JNK) signalling to STMN family
      proteins has been implicated specifically in neuronal maturation, degeneration
      and cell stress responses more broadly. Previously, we characterized mechanisms
      underlying JNK phosphorylation of STMN at proline-flanked serine residues (Ser25
      and Ser38) that are conserved across STMN-like proteins. In this study, we
      demonstrated using in vitro kinase assays and alanine replacement of serine
      residues that JNK phosphorylated the STMN-like domain (SLD) of SCG10 on Ser73,
      consistent with our previous finding that STMN Ser38 was the primary JNK target
      site. In addition, we confirmed that a JNK binding motif ((41)KKKDLSL(47)) that
      facilitates JNK targeting of STMN is conserved in SCG10. In contrast, SCLIP was
      phosphorylated by JNK primarily on Ser60 which corresponds to Ser25 on STMN.
      Moreover, although the JNK-binding motif identified in STMN and SCG10 was not
      conserved in SCLIP, JNK phosphorylation of SCLIP was inhibited by a substrate
      competitive peptide (TI-JIP) highlighting kinase-substrate interaction as
      required for JNK targeting. Thus, STMN and SCG10 are similarly targeted by JNK
      but there are clear differences in JNK recognition and phosphorylation of the
      closely related family member, SCLIP. 

PMID- 24589735
TI  - Dux4 induces cell cycle arrest at G1 phase through upregulation of p21
      expression.
AB  - It has been implicated that Dux4 plays crucial roles in development of
      facioscapulohumeral dystrophy. But the underlying myopathic mechanisms and
      related down-stream events of this retrogene were far from clear. Here, we
      reported that overexpression of Dux4 in a cell model TE671 reduced cell
      proliferation rate, and increased G1 phase accumulation. We also determined the
      impact of Dux4 on p53/p21 signal pathway, which controls the checkpoint in cell
      cycle progression. Overexpression of Dux4 increased p21 mRNA and protein level,
      while expression of p53, phospho-p53 remained unchanged. Silencing p21 rescued
      Dux4 mediated proliferation defect and cell cycle arrest. Furthermore, we
      demonstrated that enhanced Dux4 expression increased p21 promoter activity and
      elevated expression of Sp1 transcription factor. Mutation of Sp1 binding site
      decreased dux4 induced p21 promoter activation. Chromatin immunoprecipitation
      (ChIP) assays confirmed the Dux4-induced binding of Sp1 to p21 promoter in vivo.
      These results suggest that Dux4 might induce proliferation inhibition and G1
      phase arrest through upregulation of p21. 

PMID- 24589736
TI  - Bidirectional motility of the fission yeast kinesin-5, Cut7.
AB  - Kinesin-5 is a homotetrameric motor with its motor domain at the N-terminus.
      Kinesin-5 crosslinks microtubules and functions in separating spindle poles
      during mitosis. In this study, the motile properties of Cut7, fission yeast
      kinesin-5, were examined for the first time. In in vitro motility assays, full
      length Cut7 moved toward minus-end of microtubules, but the N-terminal half of
      Cut7 moved toward the opposite direction. Furthermore, additional truncated
      constructs lacking the N-terminal or C-terminal regions, but still contained the
      motor domain, did not switch the motile direction. These indicated that Cut7 was
      a bidirectional motor, and microtubule binding regions at the N-terminus and C
      terminus were not involved in its directionality. 

PMID- 24589737
TI  - WITHDRAWN: Type III restriction-modification enzyme EcoP15I's base flipping
      mechanism and its mismatch cleavage on two head-to-head oriented recognition
      sites.
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- 24589738
TI  - Transcriptional regulation of miR-146b by C/EBPbeta LAP2 in esophageal cancer
      cells.
AB  - Recent clinical study indicated that up-regulation of miR-146b was associated
      with poor overall survival of patients in esophageal squamous cell carcinoma.
      However, the underlying mechanism of miR-146b dysregulation remains to be
      explored. Here we report that miR-146b promotes cell proliferation and inhibits
      cell apoptosis in esophageal cancer cell lines. Mechanismly, two C/EBPbeta
      binding motifs are located in the miR-146b promoter conserved region. Among the
      three isoforms of C/EBPbeta, C/EBPbeta LAP2 positively regulated miR-146b
      expression and increases miR-146b levels in a dose-dependent manner through
      transcription activation of miR-146b gene. Together, these results suggest a miR
      146b regulatory mechanism involving C/EBPbeta, which may contribute to the up
      regulation of miR-146b in esophageal squamous cell carcinoma.

PMID- 24589739
TI  - Rigidity and resistance of larval- and adult schistosomes-medium interface.
AB  - Schistosomiasis is second only to malaria in prevalence and severity, and is
      still a major health problem in many tropical countries worldwide with about 200
      300 million cases and with more than 800 million people at risk of infection.
      Based on these data, the World Health Organization recommends fostering research
      efforts for understanding at any level the mechanisms of the infection and then
      decreasing the social and economical impact of schistosomiasis. A key role is
      played by the parasite apical lipid membrane, which is entirely impervious to the
      surrounding elements of the immune system. We have previously demonstrated that
      the interaction between schistosomes and surrounding medium is governed by a
      parasite surface membrane sphingomyelin-based hydrogen barrier. In the present
      article, the elastic contribution to the total motion as a function of the
      exchanged wave-vector Q and the mean square displacement values for Schistosoma
      mansoni larvae and worms and Schistosomahaematobium worms have been evaluated by
      quasi elastic neutron scattering (QENS). The results point out that S. mansoni
      larvae show a smaller mean square displacement in comparison to S. mansoni and S.
      haematobium worms. These values increased by repeating the measurements after one
      day. These differences, which are analogous to those observed for the diffusion
      coefficient we previously evaluated, are interpreted in terms of rigidity of the
      parasite-medium interaction. S. mansoni larvae are the most rigid systems, while
      S. haematobium worms are the most flexible. In addition, temperature and hypoxia
      induce a weakening of the schistosome-medium interaction. These evidences are
      related to the strength of the hydrogen-bonded interaction between parasites and
      environment that we previously determined. We have shown that S. mansoni worms
      are characterized by a weakened interaction in respect to the larvae, while the
      S. haematobium worms more weakly interact with the surrounding medium than S.
      mansoni. The present QENS analysis allowed us to characterize the rigidity of
      larval- and adult S. mansoni and S. haematobium-host interface and to relate it
      to the parasite resistance to the hostile elements of the surrounding medium and
      to the immune effectors attack. 

PMID- 24589740
TI  - It tastes as good as it looks! The effect of food presentation on liking for the
      flavor of food.
AB  - Diners in a restaurant were served the same meal (composed of a sauteed chicken
      breast with a fines herbes sauce, brown rice pilaf, and sauteed green beans with
      toasted almonds served on a round white china plate). The same food was presented
      in two different arrangements on two different nights. Although the two
      presentations were judged as equally "neat", one was judged as more attractive.
      Subjects reported liking the food on the plate (when all items were judged
      together) more when it was presented in the more attractive than the less
      attractive manner. When food items were judged separately, subjects reported
      liking the chicken and the sauce significantly more when presented in the more
      attractive manner. Subjects also reported more positive responses to the brown
      rice pilaf when presented in the more attractive plating style. How attractively
      food is plated can affect liking for the flavor of the food and could be used to
      increase acceptance of "healthy" foods.

PMID- 24589741
TI  - Multiple interfaces in self-assembled breath figures.
AB  - This feature article describes the multiple interfaces in the breath figure (BF)
      method toward functional honeycomb films with ordered pores. If a drop of polymer
      solution in a volatile solvent such as carbon disulphide is placed in a humid
      environment, evaporative cooling leads to self-assembled arrays of condensed
      water droplets. After evaporation of the solvent and water, patterned pores can
      be formed. During this BF process, the interfaces between the solution and the
      substrate, the solution and water droplets, and the film surface and air play
      extremely important roles in determining both the structures and functions of the
      honeycomb films. Progress in the BF method is reviewed by emphasizing the roles
      of the interfacial interactions. The applications of hierarchical and functional
      honeycomb films in separation, biocatalysis, biosensing, templating, stimuli
      responsive surfaces and adhesive surfaces are also discussed. 

PMID- 24589742
TI  - 1-Dimensional AgVO3 nanowires hybrid with 2-dimensional graphene nanosheets to
      create 3-dimensional composite aerogels and their improved electrochemical
      properties.
AB  - Three-dimensional (3D) porous composite aerogels have been synthesized via an
      innovative in situ hydrothermal method assisted by a freeze-drying process. In
      this hybrid structure, one-dimensional (1D) AgVO3 nanowires are uniformly
      dispersed on two-dimensional (2D) graphene nanosheet surfaces and/or are
      penetrated through the graphene sheets, forming 3D porous composite aerogels. As
      cathode materials for lithium-ion batteries, the composite aerogels exhibit high
      discharge capacity, excellent rate capability, and good cycling stability. 

PMID- 24589744
TI  - Electronic structure and optical band gap determination of NiFe2O4.
AB  - In a theoretical study we investigate the electronic structure and band gap of
      the inverse spinel ferrite NiFe2O4. The experimental optical absorption spectrum
      is accurately reproduced by fitting the Tran-Blaha parameter in the modified
      Becke-Johnson potential. The accuracy of the commonly applied Tauc plot to find
      the optical gap is assessed based on the computed spectra and we find that this
      approach can lead to a misinterpretation of the experimental data. The minimum
      gap of NiFe2O4 is found to be a 1.53 eV wide indirect gap, which is located in
      the minority spin channel. 

PMID- 24589745
TI  - Cigarette smoking, educational level and total and site-specific cancer: a cohort
      study in men in Lithuania.
AB  - Smoking is an established risk factor for cancer. However, most studies have been
      carried out on western populations, and less is known about the impact in central
      and eastern Europe. Our objective was to investigate the association between
      cigarette smoking, educational level and risk of cancer in a Lithuanian
      population-based cohort study. The study included 6976 men initially free from
      cancer. During the follow-up (1978-2008), 1780 cancer cases were identified. Cox
      proportional hazards models were used to estimate hazard ratios (HRs) and
      corresponding 95% confidence intervals (95% CIs). In addition, the burden of
      cancer attributable to smoking was assessed by the population attributable
      fraction. Following adjustment for age, education, alcohol consumption and BMI,
      for current compared with never smokers, highly significant and strongly elevated
      estimates were found for total (HR=1.79, 95% CI 1.59-2.02), tobacco-related
      (HR=2.52, 95% CI 2.16-2.95), upper aerodigestive tract (UADT) (HR=5.77, 95% CI
      2.73-12.21), lung (HR=10.47, 95% CI 6.74-16.25), bladder (HR=3.31, 95% CI 1.71
      6.41) and liver (HR=4.64, 95% CI 1.53-14.08) cancer. Findings suggest a lower
      risk of prostate cancer in current smokers. In addition, the occurrence of lung
      and UADT cancer was significantly elevated in men in the lowest educational
      attainment category. If smoking had not occurred, ~23% of total cancer, 37% of
      tobacco-related, 77% of lung, 58% of UADT, 43% of liver and 45% of bladder cancer
      cases could have been prevented in this cohort of men. Cancer-control strategies
      focused on reducing smoking should be a public health priority. 

PMID- 24589746
TI  - A mortality study of workers exposed to insoluble forms of beryllium.
AB  - This study investigated lung cancer and other diseases related to insoluble
      beryllium compounds. A cohort of 4950 workers from four US insoluble beryllium
      manufacturing facilities were followed through 2009. Expected deaths were
      calculated using local and national rates. On the basis of local rates, all-cause
      mortality was significantly reduced. Mortality from lung cancer (standardized
      mortality ratio 96.0; 95% confidence interval 80.0, 114.3) and from nonmalignant
      respiratory diseases was also reduced. There were no significant trends for
      either cause of death according to duration of employment or time since first
      employment. Uterine cancer among women was the only cause of death with a
      significantly increased standardized mortality ratio. Five of the seven women
      worked in office jobs. This study confirmed the lack of an increase in mortality
      from lung cancer and nonmalignant respiratory diseases related to insoluble
      beryllium compounds. 

PMID- 24589747
TI  - Preferential production of IgG1, IL-4 and IL-10 in MuSK-immunized mice.
AB  - Myasthenia gravis (MG) is an autoimmune disease characterized by muscle weakness
      associated with acetylcholine receptor (AChR), muscle-specific receptor kinase
      (MuSK) or low-density lipoprotein receptor-related protein 4 (LRP4)-antibodies.
      MuSK-antibodies are predominantly of the non-complement fixing IgG4 isotype. The
      MuSK associated experimental autoimmune myasthenia gravis (EAMG) model was
      established in mice to investigate immunoglobulin (Ig) and cytokine responses
      related with MuSK immunity. C57BL/6 (B6) mice immunized with 30MUg of recombinant
      human MuSK in incomplete or complete Freund's adjuvant (CFA) showed significant
      EAMG susceptibility (>80% incidence). Although mice immunized with 10MUg of MuSK
      had lower EAMG incidence (14.3%), serum MuSK-antibody levels were comparable to
      mice immunized with 30MUg MuSK. While MuSK immunization stimulated production of
      all antibody isotypes, non-complement fixing IgG1 was the dominant anti-MuSK Ig
      isotype in both sera and neuromuscular junctions. Moreover, MuSK immunized IgG1
      knockout mice showed very low serum MuSK-antibody levels. Sera and MuSK
      stimulated lymph node cell supernatants of MuSK immunized mice showed
      significantly higher levels of IL-4 and IL-10 (but not IFN-gamma and IL-12), than
      those of CFA immunized mice. Our results suggest that through activation of Th2
      type cells, anti-MuSK immunity promotes production of IL-4, which in turn
      activates anti-MuSK IgG1, the mouse analog of human IgG4. These findings might
      provide clues for the pathogenesis of other IgG4-related diseases as well as
      development of disease specific treatment methods (e.g. specific IgG4 inhibitors)
      for MuSK-related MG. 

PMID- 24589748
TI  - In Black Africans with rheumatoid arthritis, ACPA recognize citrullinated
      fibrinogen and the derived peptides alpha36-50Cit38,42 and beta60-74Cit60,72,74,
      like in Caucasians.
AB  - Well documented in Caucasians and Asians, the diagnostic value of anti-CCP2
      antibodies has been confirmed in Black African populations. However,
      autoantibodies to other citrullinated peptides/proteins and their fine
      specificities have not yet been studied. Here, we show that in Cameroonian
      patients, anti-citrullinated fibrinogen autoantibodies (AhFibA) are sensitive
      (73%) diagnostic markers for RA. We also determine that autoantibodies directed
      to alpha36-50Cit38,42 or beta60-74Cit60,72,74 peptides which bear the
      immunodominant epitopes of citrullinated fibrin, are present in similar
      proportions in Black Africans and Caucasians with 25/56 (45%) and 41/56 (73%)
      positive RA-sera in Cameroonians, respectively. They also account for almost all
      the AhFibA reactivities since 38/41 (93%) AhFibA-positive sera contain anti
      alpha36-50Cit38,42 and/or anti-beta60-74Cit60,72,74 autoantibodies. Finally, HLA
      DRB1 SE alleles were associated with higher titres of AhFibA and anti-beta60
      74Cit60,72,74 autoantibodies. In the genetic and environmental backgrounds of
      Black Africans, AhFibA are a hallmark of RA like in Caucasians, moreover they
      recognize the same fibrin epitopes.

PMID- 24589749
TI  - Identifying functional anti-Staphylococcus aureus antibodies by sequencing
      antibody repertoires of patient plasmablasts.
AB  - Infection by Staphylococcus aureus is on the rise, and there is a need for a
      better understanding of host immune responses that combat S. aureus. Here we use
      DNA barcoding to enable deep sequencing of the paired heavy- and light-chain
      immunoglobulin genes expressed by individual plasmablasts derived from S. aureus
      infected humans. Bioinformatic analysis of the antibody repertoires revealed
      clonal families of heavy-chain sequences and enabled rational selection of
      antibodies for recombinant expression. Of the ten recombinant antibodies
      produced, seven bound to S. aureus, of which four promoted opsonophagocytosis of
      S. aureus. Five of the antibodies bound to known S. aureus cell-surface antigens,
      including fibronectin-binding protein A. Fibronectin-binding protein A-specific
      antibodies were isolated from two independent S. aureus-infected patients and
      mediated neutrophil killing of S. aureus in in vitro assays. Thus, our DNA
      barcoding approach enabled efficient identification of antibodies involved in
      protective host antibody responses against S. aureus.

PMID- 24589750
TI  - Maxillary expansion therapy with plates featuring a transverse screw:
      implications of patient compliance with wear-time and screw activation
      requirements.
AB  - OBJECTIVE: The goal of the present work was to determine the influence of screw
      activation rates and electronically tracked wear times on transverse maxillary
      expansion with removable orthodontic appliances. METHODS: In all, 28 patients
      were included in an open prospective observational study covering approximately 6
      months of maxillary transverse expansion. In each of these patients, the
      maxillary plate appliance used for treatment was fitted with a wear-time sensor
      to document wear time for the duration of the study. Patients were instructed to
      activate the transverse expansion screw in their plate appliance by 0.2 mm/week.
      The resultant gap-width increases were monitored with a caliper over three follow
      up appointments scheduled at 2-month intervals. RESULTS: Largely linear increases
      in gap width due to screw activation were only noted within the first 4 months of
      treatment. The mean increases in gap width fell short of the values that were
      anticipated after calculations. Longer daily wear times were, on average,
      associated with larger gap widths. CONCLUSION: Treatment can be objectively
      monitored by referring to wear-time tracking and by measuring increases in gap
      width, thus, ensuring that the appliance fits well. In this way, the process can
      be customized to serve individual needs and to better utilize the full potential
      of therapy.

PMID- 24589752
TI  - The transformation of primary care: are general practitioners ready?

PMID- 24589753
TI  - A patient safety model for patients with ventricular assist devices undergoing
      noncardiac procedures.

PMID- 24589751
TI  - In vitro reconstitution of pancreatic islets.
AB  - The lack of transplantable pancreatic islets is a serious problem that affects
      the treatment of patients with type 1 diabetes mellitus. Beta cells can be
      induced from various sources of stem or progenitor cells, including induced
      pluripotent stem cells in the near future; however, the reconstitution of islets
      from beta cells in culture dishes is challenging. The generation of highly
      functional islets may require three-dimensional spherical cultures that resemble
      intact islets. This review discusses recent advances in the reconstitution of
      islets. Several factors affect the reconstitution of pseudoislets with higher
      functions, such as architectural similarity, cell-to-cell contact, and the
      production method. The actual transplantation of naked or encapsulated
      pseudoislets and islet-like cell clusters from various stem cell sources is also
      discussed. Advancing our understanding of the methods used to reconstitute
      pseudoislets should expand the range of potential strategies available for
      developing de novo islets for therapeutic applications. 

PMID- 24589755
TI  - [Bilateral diffuse uveal melanocytic proliferation in a patient with metastatic
      breast cancer].
AB  - A 64-year-old female patient with a history of metastatic breast cancer presented
      with bilateral deterioration of visual acuity over a period of several weeks.
      Examination revealed patchy fundus pigmentation, serous retinal detachment and
      cataract in both eyes. After diagnosis of a bilateral diffuse uveal melanocytic
      proliferation (BDUMP) and due to disease progression, a course of plasmapheresis
      three times a week over a period of 2 weeks was initiated. Apart from the
      occurrence of peripheral edemas the therapy was well-tolerated by the patient.
      Treatment success could not be evaluated because the patient died a short time
      later. This is the first reported case of BDUMP due to breast cancer. 

PMID- 24589756
TI  - [Epiphora with pressure-indolent swelling of the medial canthus].

PMID- 24589757
TI  - The effects of pesticide exposure on ultraviolet-B radiation avoidance behavior
      in tadpoles.
AB  - Effects of contaminants on behavior may have important consequences on wildlife
      populations because behaviors such as predation, predator avoidance,
      reproduction, and social interaction can affect population dynamics. As a common
      environmental stressor, ultraviolet-B (UVB) radiation causes various deleterious
      effects and some aquatic organisms actively avoid UVB radiation in water.
      However, the extent to which environmental contaminants can impair UVB avoidance
      has not been evaluated, which may cause greater UVB exposure and toxicity. In the
      present study, we used Xenopus laevis tadpoles to determine if acute exposure to
      sublethal concentrations of agricultural chemicals can alter tadpole response to
      UVB radiation. We exposed tadpoles to four pesticides (malathion, endosulfan,
      alpha-cypermethrin, and chlorothalonil) for 96 h. At the end of the exposure,
      tadpoles were transferred to tanks divided into UVB and no-UVB areas. We observed
      tadpoles for 30 min and recorded time spent in the UVB area. We compared the
      proportion of time tadpoles spent in the UVB area among different concentrations
      for each pesticide. There was no significant difference between FETAX control and
      solvent control tadpoles. When combined, control tadpoles spent less than half of
      the time in the UVB area indicating that X. laevis tadpoles exhibit UVB avoidance
      behavior. Tadpoles exposed to 5 MUg/L endosulfan spent significantly more time
      under UVB than control tadpoles. Other pesticides had no effect on tadpole UVB
      avoidance behavior. Our results suggest that some neurotoxic pesticides can
      affect UVB avoidance in larval amphibians, which may increase their exposure and
      subsequently the risk of UVB-induced damage. The present study highlights the
      importance of examining the interaction between two stressors that co-occur
      across broad spatial scales and to consider behavioral alteration when evaluating
      the risk of pesticides to amphibians.

PMID- 24589758
TI  - Characterization of combined cross-linked enzyme aggregates from laccase,
      versatile peroxidase and glucose oxidase, and their utilization for the
      elimination of pharmaceuticals.
AB  - In order to transform a wide range of pharmaceutically active compounds (PhACs),
      the three oxidative enzymes laccase (Lac) from Trametes versicolor, versatile
      peroxidase (VP) from Bjerkandera adusta and glucose oxidase (GOD) from
      Aspergillus niger were concomitantly cross-linked after aggregation, thus, making
      a combined cross-linked enzyme aggregate (combi-CLEA) that was versatile and
      involved in an enzymatic cascade reaction. From the initial enzymes about 30% of
      initial laccase activity was recovered along with 40% for each of VP and GOD. The
      combi-CLEA showed good results in conditions close to those of real wastewater
      (neutral pH and medium temperature) as well as a good ability to resist to
      denaturing conditions such as high temperature (60 degrees C) and low pH (3).
      Batch experiments were realized to test the free enzyme's ability to degrade, a
      PhACs cocktail, mainly in a synthetic wastewater containing acetaminophen,
      naproxen, mefenamic acid, indometacin, diclofenac, ketoprofen, caffeine,
      diazepam, ciprofloxacin, trimethoprim, fenofibrate and bezafibrate, carbamazepine
      and its by-product 10-11 epoxy-carbamazepine. High removal was achieved (more
      than 80%) for the five first compounds. Then, the elimination ability of the
      combi-CLEA with or without hydrogen peroxide, glucose or manganese sulfate was
      determined. Globally, our results demonstrated that VP has a wider removal
      spectrum than Lac. These removal features are enhanced under more specific
      conditions, whereas the combi-CLEA combined advantages of both VP and laccase.
      Finally, the elimination of PhACs in a municipal wastewater treatment plant
      effluent using the combi-CLEA was marginally investigated. Concentrations of most
      of the selected PhACs were below the limit of quantification (lower than 20 ng/L)
      except for acetaminophen. Its combi-CLEA-mediated removal reached up to 25%.

PMID- 24589759
TI  - The role of cassiterite controlling arsenic mobility in an abandoned stanniferous
      tailings impoundment at Llallagua, Bolivia.
AB  - The surface water contamination by potentially toxic elements (PTE) leached from
      mine tailings is a major environmental concern. However, the formation of
      insoluble solid phases can control the mobility of PTE, with subsequent decrease
      of the risk that tailings suppose to the environment. We characterized the
      tailings from a tin inactive mine in Llallagua, Bolivia in order to assess the
      risk for surface water quality. These tailings contain high concentrations of
      PTE, with up to 94,344 mg/kg Fe, 9,135 mg/kg Sn, 4,606 mg/kg As, 1,362 mg/kg Cu,
      1,220 mg/kg Zn, 955 mg/kg Pb and 151 mg/kg Cd. Oxidation of sulfide minerals in
      these tailings generates acid leachates (pH=2.5-3.5), rich in SO4(2-) and
      dissolved PTE, thereby releasing contaminants to the surface waters.
      Nevertheless, the concentrations of dissolved Sn, As and Pb in acid leachates are
      low (Sn<0.01 mg/L; As=0.25-2.55 mg/L; Pb<0.05 mg/L). This indicates that, for the
      most part, Sn, As and Pb are being retained by the solid phases in the
      impoundment, so that these elements are not reaching the surface waters. Fe
      bearing cassiterite-an insoluble and weathering-resistant oxide mineral-is
      abundant in the studied tailing deposits; it should be the main solid phase
      controlling Sn and As mobility in the impoundment. Additionally, jarosite and
      plumbojarosite, identified among the secondary minerals, could also play an
      important role controlling the mobility of As and Pb. Taking into account (a) the
      low solubility constants of cassiterite (Ksp=10(-64.2)), jarosite (Ksp=10(-11))
      and plumbojarosite (Ksp=10(-28.66)), and (b) the stability of these minerals
      under acidic conditions, we can conclude that they control the long-term fate of
      Sn, As and Pb in the studied tailings.

PMID- 24589760
TI  - Clinical analysis on 33 patients with hypothalamic syndrome in Chinese children.
AB  - AIM: To investigate the etiology and clinical characteristics of hypothalamic
      syndrome in Chinese children. METHODS: Thirty-three cases of hypothalamic
      syndrome were analyzed for etiology, initial symptoms, and clinical
      characteristics. RESULTS: All of the 33 patients manifested symptoms of
      hypothalamic dysfunction and disorders of the hypothalamus-hypophysis-target
      gland axis. Fourteen patients were diagnosed with an intracranial tumor by
      magnetic resonance imaging (MRI) examination, four patients had postoperative
      intracranial tumors, one had received radiotherapy for suprasellar germinoma, one
      was hypothalamic-pituitary dysplasia, one had a history of viral encephalitis,
      and in 12 patients, the cause was unknown. The most common presenting symptoms
      were polydipsia/polyuria and eating disorders. CONCLUSION: Intracranial tumor is
      an important cause of hypothalamic syndrome in children, with germinoma the most
      common. Polydipsia, polyuria, and eating disorders are typical presenting
      symptoms. Long-term follow-up is needed for patients presenting with central
      diabetes insipidus, eating disorders or hypothalamic syndrome of unknown
      etiology. In addition, periodic pituitary MRI scanning is necessary to find
      potential intracranial tumors that may arise at any time.

PMID- 24589761
TI  - How to discover a metabolic pathway? An update on gene identification in
      aliphatic glucosinolate biosynthesis, regulation and transport.
AB  - Identification of enzymes, regulators and transporters involved in different
      metabolic processes is the foundation to understand how organisms function. There
      are, however, many difficulties in identifying candidate genes as well as in
      proving their in vivo roles. In this review, we describe different approaches
      utilized in Arabidopsis thaliana to identify gene candidates and experiments
      required to prove the function of a given candidate. For example, we use the
      production of methionine-derived aliphatic glucosinolates that represent major
      defence compounds in A. thaliana. Nearly all biosynthetic genes, as well as the
      first sets of regulators and transporters, have been identified. An array of
      approaches, i.e. classical mapping, quantitative trait loci (QTL) mapping, eQTL
      mapping, co-expression, genome wide association studies (GWAS), mutant screens
      and phylogenetic analyses, has been exploited to increase the number of
      identified genes. Here we summarize the lessons learned from the different
      approaches used over the years with the aim to help designing and combining new
      approaches in the future.

PMID- 24589762
TI  - Southward spreading of the Fukushima-derived radiocesium across the Kuroshio
      Extension in the North Pacific.
AB  - The accident of the Fukushima Dai-ichi nuclear power plant in March 2011 released
      a large amount of radiocesium into the North Pacific Ocean. Vertical
      distributions of Fukushima-derived radiocesium were measured at stations along
      the 149 degrees E meridian in the western North Pacific during the winter of
      2012. In the subtropical region, to the south of the Kuroshio Extension, we found
      a subsurface radiocesium maximum at a depth of about 300 m. It is concluded that
      atmospheric-deposited radiocesium south of the Kuroshio Extension just after the
      accident had been transported not only eastward along with surface currents but
      also southward due to formation/subduction of subtropical mode waters within
      about 10 months after the accident. The total amount of decay-corrected (134)Cs
      in the mode water was an estimated about 6 PBq corresponding to 10-60% of the
      total inventory of Fukushima-derived (134)Cs in the North Pacific Ocean. 

PMID- 24589763
TI  - Sources of prescription opioid pain relievers by frequency of past-year
      nonmedical use United States, 2008-2011.

PMID- 24589764
TI  - Consultant pharmacists, advanced practice nurses, and the interdisciplinary team.
AB  - Although in geriatrics we are better than many other clinical disciplines in
      terms of providing interdisciplinary care to older adults, I hope that we will
      continue to recognize how much more could actually be done. Before addressing the
      relationship between advanced practice nurses (APNs) and consultant pharmacists
      in real world settings, I want to review teamwork in geriatrics in general. It is
      critical to define what we mean by team, what type of team, and what the goals
      are of this teamwork. 

PMID- 24589765
TI  - Drug Burden Index score and anticholinergic risk scale as predictors of
      readmission to the hospital.
AB  - OBJECTIVE: Determine the association between different measures of drug exposure
      such as an increased Drug Burden Index (DBI) and a higher Anticholinergic Risk
      Scale (ARS) score in vulnerable elders and risk of readmission to the hospital.
      DESIGN: The study is a retrospective cohort comparing ARS and DBI between
      patients readmitted and not readmitted to the hospital within 30 days of initial
      admission. Data collected included drugs considered to have anticholinergic,
      sedative, or both types of properties (Appendix 1), medication strengths, doses
      per day, patient age, Vulnerable Elders Survey (VES-13) score upon admission,
      patient diagnoses, and rates of admission. SETTING: Nonprofit, 838-bed, regional
      health system of four hospitals. PATIENTS, PARTICIPANTS: Patients were included
      in the study if they were admitted to a hospital floor, were 65 years of age or
      older, were assessed using VES-13, and did not have routinely visiting family to
      engage them as observed by floor nurses. INTERVENTIONS: None; retrospective
      study. MAIN OUTCOME MEASURES: Readmission rate. RESULTS: The mean difference in
      DBI and ARS scores were higher in the readmitted group. Hydrocodone and
      hydroxyzine were the most commonly used drugs in the readmitted group that were
      considered when determining DBI. CONCLUSION: There is a role for screening and
      clinical intervention in vulnerable elders using DBI and ARS to help identify
      those at greatest risk for readmission to the hospital.

PMID- 24589766
TI  - Dabigatran for stroke prevention in nonvalvular atrial fibrillation: focus in the
      geriatric population.
AB  - OBJECTIVE: To evaluate the safety and efficacy of dabigatran for stroke
      prevention in the elderly population. DATA SOURCES: MEDLINE (1948-June 2013), Web
      of Science (1980-June 2013), and Google Scholar were used to identify relevant
      literature. Search terms included dabigatran, dabigatran etexilate, geriatric,
      elderly. STUDY SELECTION: All articles evaluating the use of dabigatran in the
      elderly were considered for inclusion. Data derived from controlled clinical
      studies were given priority for inclusion. DATA EXTRACTION: Only the Randomized
      Evaluation of Long-Term Anticoagulant Therapy trial has evaluated dabigatran
      etexilate for the prevention of stroke in nonvalvular atrial fibrillation. A post
      hoc analysis of this study was completed to identify the risks and benefits of
      therapy in patients 75 years of age and older. Numerous case reports and case
      series have been published that suggest an increased risk of bleeding in the
      elderly. Large observational studies, however, have not supported the hypotheses
      generated by these case reports. DATA SYNTHESIS: Since the approval of dabigatran
      etexilate, numerous case reports have suggested the potential dangers of bleeding
      complications, especially given that there is no known antidote. Observational
      studies have challenged these case reports and suggest that the increased risk of
      bleeding is similar or lower compared with warfarin therapy. The increased
      reporting of bleeding complications may be a result of reporting bias.
      CONCLUSIONS: Advanced age alone should not exclude the use of dabigatran.
      Clinicians should base their decision on patient characteristics and careful
      assessment of risk versus benefit.

PMID- 24589767
TI  - Care transitions in elderly heart failure patients: current practices and the
      pharmacist's role.
AB  - OBJECTIVE: To provide an up-to-date review of current care transitions in elderly
      heart failure (HF) patients and assess the role of the pharmacist in improving
      patient care. DATA SOURCE: A PubMed search of articles in the English language
      published between 1995 and May 2013 was done using a combination of the following
      words: discharge counseling, elderly, heart failure, multidisciplinary team,
      pharmacist, pharmacy, readmission, transition of care. STUDY SELECTION/DATA
      EXTRACTION: Relevant original studies, review articles, and guidelines were
      assessed for current practices in HF transitions of care. References from the
      above literature were also evaluated for relevance. Articles were selected for
      inclusion based on relevance to the topic, detailed methods, and clear,
      comprehensive results. DATA SYNTHESIS: The incidence of HF is rapidly increasing,
      and emphasis has been placed on reducing readmissions. Although present practices
      are primarily nurse-led, pharmacists are in a key position to educate patients
      through multidisciplinary teams, discharge counseling, and medication
      reconciliation. Because of concerns about pharmacist provider status and
      reimbursement, pharmacists should identify areas in their practices where they
      can intervene and improve patient care to reduce readmissions. CONCLUSION:
      Pharmacists are an integral part of the multidisciplinary team in optimizing care
      for elderly HF patients to prevent readmissions.

PMID- 24589768
TI  - Donepezil-induced mania.
AB  - OBJECTIVE: To report a case of mania associated with the titration of donepezil
      in an elderly patient. SETTING: A 400-bed academic acute care psychiatric
      facility. CASE SUMMARY: A 70-year-old male with a history of paranoid
      schizophrenia, alcohol dependence, and mild cognitive impairment was admitted
      after concerns that he was responding to internal stimuli and exhibited increased
      disorganization. The patient was initiated on quetiapine, titrated to 500 mg at
      bedtime, to address disorganization, hallucinations, and poor sleep. After
      improvement of psychotic symptoms and assessment of cognitive function, donepezil
      5 mg daily was initiated and titrated to 10 mg daily after two weeks. Days
      following the increase of donepezil to 10 mg daily, the patient exhibited
      symptoms of mania and became hyperverbal with elevated mood and agitation. A
      decreased need for sleep with an increase in cleaning activities throughout the
      day was noted. Donepezil was suspected to have induced the new symptoms and was
      discontinued. Following discontinuation, the manic symptoms completely resolved
      over a two-week period. CONCLUSION: The titration of donepezil was associated
      with the onset of mania. Previous trials involving off-label donepezil use in
      patients with bipolar disorder, but not schizophrenia, have reported the
      development of manic symptoms. Although rare, there is mounting evidence that
      donepezil is associated with the emergence of mania. Clinicians should be aware
      of this potential side effect in all patients treated with donepezil.

PMID- 24589769
TI  - Key aspects and health care benefits of patient-centered medical homes part 1 of
      3.
AB  - The concept of patient-centered medical homes (PCMHs) is one of the latest
      efforts to provide higher quality of life for patients while aiming to reduce
      overall health care costs. As part of this health care reform effort, PCMHs
      strive to provide patient-centered, coordinated, effective, and efficient care
      that leads to long-term relationships with patients. The objective of this three
      part series is to provide a comprehensive review of the PCMH for health care
      practice sites and professionals, its key features, recognition of quality
      programs, support and payment models from government and third-party insurers,
      and patient and professional benefits. Part 1 describes the history and
      development of PCMHs, the overall concept of the health care model, and the
      process that is used to recognize quality PCMHs. Because of the current
      weaknesses and deficiencies in the United States' health care system, there is a
      definitive need for the establishment and expansion of PCMHs. 

PMID- 24589770
TI  - Lipoprotein-associated lysolipids are differentially involved in high-density
      lipoprotein- and its oxidized form-induced neurite remodeling in PC12 cells.
AB  - Oxidatively damaged proteins and lipid peroxidation products have been shown to
      accumulate in the brain of neurodegenerative diseases, such as Alzheimer's
      disease and multiple sclerosis, and oxidized lipoprotein is considered to be
      toxic and neurodegenerative. However, the role of lipoprotein and its oxidized
      form in neurite remodeling has not been well understood. In the present study, we
      have aimed to clarify whether and, if so, how high-density lipoprotein (HDL) and
      oxidized HDL (oxHDL) affect neuritogenesis. In the presence of nerve growth
      factor, exposure of PC12 cells to either HDL or oxHDL induces a rapid neurite
      retraction, which is followed by re-outgrowth of neurites in either case;
      however, oxHDL-treated cells exhibit much longer outgrowths than do basal and HDL
      treated cells. Thus, processes in the morphological changes of neuronal cells
      after lipoprotein treatment are composed of two phases: the reversible retraction
      phase and the extension phase. Characterization of the active fractions of lipids
      and experiments with desensitization and knockdown of receptors have indicated
      that the reversible retraction phase involves mainly sphingosine 1-phosphate for
      HDL and lysophosphatidic acid for oxHDL. The change in the components responsible
      for the retraction response is comparable with the change in sphingosine 1
      phosphate and lysophosphatidic acid contents by the oxidation of HDL. In the
      extension phase, lysophosphatidylcholine, which is increased by the oxidation of
      HDL, may play a stimulatory role in neurite outgrowth. We conclude that
      lipoprotein and its oxidized form differentially regulate neuritogenesis through
      lipoprotein-associated lysolipid molecules. 

PMID- 24589771
TI  - NADPH oxidase inhibition improves neurological outcome in experimental traumatic
      brain injury.
AB  - PURPOSE: Traumatic brain injury (TBI) is a worldwide health problem with
      oxidative stress recognized as a major pathogenetic factor. The present
      experimental study was designed to explore the neuroprotective effect of NADPH
      oxidase (NOX) inhibitor, apocynin, on mouse TBI. METHODS: Moderately severe
      weight-drop impact head injury was induced in adult male mice, randomly divided
      into four groups: sham, TBI, TBI+vehicle and TBI+apocynin treatment. Apocynin (50
      mg/kg) was injected intraperitoneally 30 min before TBI. The expression of NOX2
      protein was investigated using immunoblotting techniques 1 and 24h after TBI.
      Neurological score was evaluated 24h after TBI. Blood-brain barrier disruption
      was detected by Evans blue extravasation and cortical apoptosis was analyzed by
      TUNEL assay. Additionally, we assessed tissue levels of malondialdehyde (MDA).
      RESULTS: NOX2 expression increased rapidly following TBI in male mice, with an
      early peak at 1h, followed by a second peak at 24h. Pre-treatment with the NOX
      inhibitor, apocynin markedly inhibited NOX2 expression. Apocynin also attenuated
      MDA levels and TBI-induced blood-brain barrier dysfunction. In addition apocynin
      significantly attenuated TBI-induced neurological deficits and cortical
      apoptosis. CONCLUSION: Pre-treatment with apocynin effectively attenuates markers
      of cerebral oxidative stress after TBI, thus supporting the hypothesis that
      apocynin is a potential neuroprotectant and adjunct therapy for TBI patients.

PMID- 24589772
TI  - LDL cholesterol performance of beta quantification reference measurement
      procedure.
AB  - BACKGROUND: Accurate measurement of blood lipids is crucial in cardiovascular
      disease risk management. The Centers for Disease Control and Prevention (CDC)
      Cholesterol Reference Method Laboratory Network (CRMLN) has assured the accuracy
      of these measurements for over 20 years using beta quantification (BQ) method as
      reference measurement procedure (RMP) for high- and low-density lipoprotein
      cholesterol (HDL-C, LDL-C). Only limited data exist about the performance of the
      BQ RMP. METHODS: Bottom fraction cholesterol (BFC), HDL-C, and LDL-C results
      after ultracentrifugation from the CDC lipid reference laboratory and the
      Japanese CRMLN laboratory were compared using 280 serum samples measured over the
      past 15 years. Data were compared statistically using method comparison and bias
      estimation analysis. RESULTS: Regression analysis between CDC (x) and Osaka (y)
      for BFC, HDL-C, and LDL-C were y=0.988x+1.794 (R(2)=0.997), y=0.980x+1.118
      (R(2)=0.994), and y=0.987x+1.200 (R(2)=0.997), respectively. The Osaka laboratory
      met performance goals for 90% to 95% of the CDC reference values. CONCLUSIONS:
      The BQ method by the Osaka CRMLN laboratory is highly accurate and has been
      stable for over 15 years. Accurate measurement of BFC is critical for the
      determination of LDL-C.

PMID- 24589773
TI  - Rebaudioside A and cortisol metabolism: sweet news for consumers.

PMID- 24589774
TI  - Small but sturdy: small RNAs in cellular memory and epigenetics.
AB  - Cells in multicellular organisms have distinct identities characterized by their
      profiles of expressed genes. Cell identities can be stable over a long time and
      through multiple cellular divisions but are also responsive to extracellular
      signals. Since the DNA sequence is identical in all cells, a "cellular memory" of
      expression profiles is achieved by what are defined as epigenetic mechanisms. Two
      major molecular principles--networks of transcription factors and maintenance of
      cis-chromatin modifications--have been implicated in maintaining cellular memory.
      Here we describe recent studies demonstrating that short noncoding RNAs can also
      provide molecular signals that define epigenetic states of cells. Small RNAs can
      act independently or cooperate with chromatin modifications to achieve long
      lasting effects necessary for cellular memory and transgenerational inheritance.

PMID- 24589775
TI  - A temporal requirement for Hippo signaling in mammary gland differentiation,
      growth, and tumorigenesis.
AB  - Despite recent progress, the physiological role of Hippo signaling in mammary
      gland development and tumorigenesis remains poorly understood. Here we show that
      the Hippo pathway is functionally dispensable in virgin mammary glands but
      specifically required during pregnancy. In contrast to many other tissues,
      hyperactivation of YAP in mammary epithelia does not induce hyperplasia but leads
      to defects in terminal differentiation. Interestingly, loss of YAP causes no
      obvious defects in virgin mammary glands but potently suppresses oncogene-induced
      mammary tumors. The selective requirement for YAP in oncogenic growth highlights
      the potential of YAP inhibitors as molecular targeted therapies against breast
      cancers. 

PMID- 24589776
TI  - The Gpr1/Zdbf2 locus provides new paradigms for transient and dynamic genomic
      imprinting in mammals.
AB  - Many loci maintain parent-of-origin DNA methylation only briefly after
      fertilization during mammalian development: Whether this form of transient
      genomic imprinting can impact the early embryonic transcriptome or even have life
      long consequences on genome regulation and possibly phenotypes is currently
      unknown. Here, we report a maternal germline differentially methylated region
      (DMR) at the mouse Gpr1/Zdbf2 (DBF-type zinc finger-containing protein 2) locus,
      which controls the paternal-specific expression of long isoforms of Zdbf2 (Liz)
      in the early embryo. This DMR loses parental specificity by gain of DNA
      methylation at implantation in the embryo but is maintained in extraembryonic
      tissues. As a consequence of this transient, tissue-specific maternal imprinting,
      Liz expression is restricted to the pluripotent embryo, extraembryonic tissues,
      and pluripotent male germ cells. We found that Liz potentially functions as both
      Zdbf2-coding RNA and cis-regulatory RNA. Importantly, Liz-mediated events allow a
      switch from maternal to paternal imprinted DNA methylation and from Liz to
      canonical Zdbf2 promoter use during embryonic differentiation, which are stably
      maintained through somatic life and conserved in humans. The Gpr1/Zdbf2 locus
      lacks classical imprinting histone modifications, but analysis of mutant
      embryonic stem cells reveals fine-tuned regulation of Zdbf2 dosage through DNA
      and H3K27 methylation interplay. Together, our work underlines the developmental
      and evolutionary need to ensure proper Liz/Zdbf2 dosage as a driving force for
      dynamic genomic imprinting at the Gpr1/Zdbf2 locus. 

PMID- 24589777
TI  - D-2-hydroxyglutarate produced by mutant IDH2 causes cardiomyopathy and
      neurodegeneration in mice.
AB  - Mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2) have been discovered in
      several cancer types and cause the neurometabolic syndrome D2-hydroxyglutaric
      aciduria (D2HGA). The mutant enzymes exhibit neomorphic activity resulting in
      production of D2-hydroxyglutaric acid (D-2HG). To study the pathophysiological
      consequences of the accumulation of D-2HG, we generated transgenic mice with
      conditionally activated IDH2(R140Q) and IDH2(R172K) alleles. Global induction of
      mutant IDH2 expression in adults resulted in dilated cardiomyopathy, white matter
      abnormalities throughout the central nervous system (CNS), and muscular
      dystrophy. Embryonic activation of mutant IDH2 resulted in more pronounced
      phenotypes, including runting, hydrocephalus, and shortened life span,
      recapitulating the abnormalities observed in D2HGA patients. The diseased hearts
      exhibited mitochondrial damage and glycogen accumulation with a concordant up
      regulation of genes involved in glycogen biosynthesis. Notably, mild cardiac
      hypertrophy was also observed in nude mice implanted with IDH2(R140Q)-expressing
      xenografts, suggesting that 2HG may potentially act in a paracrine fashion.
      Finally, we show that silencing of IDH2(R140Q) in mice with an inducible
      transgene restores heart function by lowering 2HG levels. Together, these
      findings indicate that inhibitors of mutant IDH2 may be beneficial in the
      treatment of D2HGA and suggest that 2HG produced by IDH mutant tumors has the
      potential to provoke a paraneoplastic condition. 

PMID- 24589778
TI  - Conserved residues in yeast initiator tRNA calibrate initiation accuracy by
      regulating preinitiation complex stability at the start codon.
AB  - Eukaryotic initiator tRNA (tRNAi) contains several highly conserved unique
      sequence features, but their importance in accurate start codon selection was
      unknown. Here we show that conserved bases throughout tRNAi, from the anticodon
      stem to acceptor stem, play key roles in ensuring the fidelity of start codon
      recognition in yeast cells. Substituting the conserved G31:C39 base pair in the
      anticodon stem with different pairs reduces accuracy (the Sui(-) [suppressor of
      initiation codon] phenotype), whereas eliminating base pairing increases accuracy
      (the Ssu(-) [suppressor of Sui(-)] phenotype). The latter defect is fully
      suppressed by a Sui(-) substitution of T-loop residue A54. These genetic data are
      paralleled by opposing effects of Sui(-) and Ssu(-) substitutions on the
      stability of methionylated tRNAi (Met-tRNA(i)) binding (in the ternary complex
      [TC] with eIF2-GTP) to reconstituted preinitiation complexes (PICs). Disrupting
      the C3:G70 base pair in the acceptor stem produces a Sui(-) phenotype and also
      reduces the rate of TC binding to 40S subunits in vitro and in vivo. Both defects
      are suppressed by an Ssu(-) substitution in eIF1A that stabilizes the open/P(OUT)
      conformation of the PIC that exists prior to start codon recognition. Our data
      indicate that these signature sequences of tRNA(i) regulate accuracy by distinct
      mechanisms, promoting the open/P(OUT) conformation of the PIC (for C3:G70) or
      destabilizing the closed/P(IN) state (for G31:C39 and A54) that is critical for
      start codon recognition.

PMID- 24589780
TI  - The impact factor: yesterday's metric?

PMID- 24589779
TI  - Structural basis for promoter specificity switching of RNA polymerase by a phage
      factor.
AB  - Transcription of DNA to RNA by DNA-dependent RNA polymerase (RNAP) is the first
      step of gene expression and a major regulation point. Bacteriophages hijack their
      host's transcription machinery and direct it to serve their needs. The gp39
      protein encoded by Thermus thermophilus phage P23-45 binds the host's RNAP and
      inhibits transcription initiation from its major "-10/-35" class promoters. Phage
      promoters belonging to the minor "extended -10" class are minimally inhibited. We
      report the crystal structure of the T. thermophilus RNAP holoenzyme complexed
      with gp39, which explains the mechanism for RNAP promoter specificity switching.
      gp39 simultaneously binds to the RNAP beta-flap domain and the C-terminal domain
      of the sigma subunit (region 4 of the sigma subunit [sigma4]), thus relocating
      the beta-flap tip and sigma4. The ~45 A displacement of sigma4 is incompatible
      with its binding to the -35 promoter consensus element, thus accounting for the
      inhibition of transcription from -10/-35 class promoters. In contrast, this
      conformational change is compatible with the recognition of extended -10 class
      promoters. These results provide the structural bases for the conformational
      modulation of the host's RNAP promoter specificity to switch gene expression
      toward supporting phage development for gp39 and, potentially, other phage
      proteins, such as T4 AsiA.

PMID- 24589781
TI  - Recent insights into the identity of mesenchymal stem cells: Implications for
      orthopaedic applications.
AB  - The ability of mesenchymal stem cells (MSCs) to differentiate in vitro into
      chondrocytes, osteocytes and myocytes holds great promise for tissue engineering.
      Skeletal defects are emerging as key targets for treatment using MSCs due to the
      high responsiveness of bone to interventions in animal models. Interest in MSCs
      has further expanded in recognition of their ability to release growth factors
      and to adjust immune responses. Despite their increasing application in clinical
      trials, the origin and role of MSCs in the development, repair and regeneration
      of organs have remained unclear. Until recently, MSCs could only be isolated in a
      process that requires culture in a laboratory; these cells were being used for
      tissue engineering without understanding their native location and function. MSCs
      isolated in this indirect way have been used in clinical trials and remain the
      reference standard cellular substrate for musculoskeletal engineering. The
      therapeutic use of autologous MSCs is currently limited by the need for ex vivo
      expansion and by heterogeneity within MSC preparations. The recent discovery that
      the walls of blood vessels harbour native precursors of MSCs has led to their
      prospective identification and isolation. MSCs may therefore now be purified from
      dispensable tissues such as lipo-aspirate and returned for clinical use in
      sufficient quantity, negating the requirement for ex vivo expansion and a second
      surgical procedure. In this annotation we provide an update on the recent
      developments in the understanding of the identity of MSCs within tissues and
      outline how this may affect their use in orthopaedic surgery in the future.

PMID- 24589782
TI  - A comparison of the use of uncemented hydroxyapatite-coated bipolar and cemented
      femoral stems in the treatment of femoral neck fractures: a case-control study.
AB  - We performed a case-control study to compare the rates of further surgery,
      revision and complications, operating time and survival in patients who were
      treated with either an uncemented hydroxyapatite-coated Corail bipolar femoral
      stem or a cemented Exeter stem for a displaced intracapsular fracture of the hip.
      The mean age of the patients in the uncemented group was 82.5 years (53 to 97)
      and in the cemented group was 82.7 years (51 to 99) We used propensity score
      matching, adjusting for age, gender and the presence or absence of dementia and
      comorbidities, to produce a matched cohort receiving an Exeter stem (n = 69) with
      which to compare the outcome of patients receiving a Corail stem (n = 69). The
      Corail had a significantly lower all-cause rate of further surgery (p = 0.016;
      odds ratio (OR) 0.18, 95% CI 0.04 to 0.84) and number of hips undergoing major
      further surgery (p = 0.029; OR 0.13, 95% CI 0.01 to 1.09). The mean operating
      time was significantly less for the Corail group than for the cemented Exeter
      group (59 min [12 to 136] vs 70 min [40 to 175], p = 0.001). The Corail group
      also had a lower risk of a peri-prosthetic fracture (p = 0.042; OR 0.19, 95% CI
      0.01 to 1.42) . There was no difference in the mortality rate between the groups.
      There were significantly fewer complications in the uncemented group, suggesting
      that the use of this stem would result in a decreased rate of morbidity in these
      frail patients. Whether this relates to an improved functional outcome remains
      unknown.

PMID- 24589783
TI  - The use of the transverse acetabular ligament in total hip replacement: An
      analysis of the orientation of the trial acetabular component using a navigation
      system.
AB  - It has recently been reported that the transverse acetabular ligament (TAL) is
      helpful in determining the position of the acetabular component in total hip
      replacement (THR). In this study we used a computer-assisted navigation system to
      determine whether the TAL is useful as a landmark in THR. The study was carried
      out in 121 consecutive patients undergoing primary THR (134 hips), including 67
      dysplastic hips (50%). There were 26 men (29 hips) and 95 women (105 hips) with a
      mean age of 60.2 years (17 to 82) at the time of operation. After identification
      of the TAL, its anteversion was measured intra-operatively by aligning the
      inferomedial rim of the trial acetabular component with the TAL using computer
      assisted navigation. The TAL was identified in 112 hips (83.6%). Intra-observer
      reproducibility in the measurement of anteversion of the TAL was high, but inter
      observer reproducibility was moderate. Each surgeon was able to align the trial
      component according to the target value of the angle of anteversion of the TAL,
      but it was clear that methods may differ among surgeons. Of the measurements of
      the angle of anteversion of the TAL, 5.4% (6 of 112 hips) were outliers from the
      safe zone. In summary, we found that the TAL is useful as a landmark when
      implanting the acetabular component within the safe zone in almost all hips, and
      to prevent it being implanted in retroversion in all hips, including dysplastic
      hips. However, as anteversion of the TAL may be excessive in a few hips, it is
      advisable to pay attention to individual variations, particularly in those with
      severe posterior pelvic tilt.

PMID- 24589784
TI  - The use of the transverse acetabular ligament for determining the orientation of
      the components in total hip replacement: a randomised controlled trial.
AB  - The orientation of the acetabular component can influence both the short- and
      long-term outcomes of total hip replacement (THR). We performed a prospective,
      randomised, controlled trial of two groups, comprising of 40 patients each, in
      order to compare freehand introduction of the component with introduction using
      the transverse acetabular ligament (TAL) as a reference for anteversion.
      Anteversion and inclination were measured on pelvic radiographs. With respect to
      anteversion, in the freehand group 22.5% of the components were outside the safe
      zone versus 0% in the transverse acetabular ligament group (p = 0.002). The mean
      angle of anteversion in the freehand group was 21 degrees  (2 degrees  to 35
      degrees ) which was significantly higher compared with 17 degrees  (2 degrees  to
      25 degrees ) in the TAL group (p = 0.004). There was a significant difference
      comparing the variations of both groups (p = 0.008). With respect to inclination,
      in the freehand group 37.5% of the components were outside the safe zone versus
      20% in the TAL group (p = 0.14). There was no significant difference regarding
      the accuracy or variation of the angle of inclination when comparing the two
      groups. The transverse acetabular ligament may be used to obtain the appropriate
      anteversion when introducing the acetabular component during THR, but not
      acetabular component inclination.

PMID- 24589785
TI  - Reconstruction of massive uncontained acetabular defects using allograft with
      cage or ring reinforcement: an assessment of the graft's ability to restore bone
      stock and its impact on the outcome of re-revision.
AB  - We retrospectively reviewed 44 consecutive patients (50 hips) who underwent
      acetabular re-revision after a failed previous revision that had been performed
      using structural or morcellised allograft bone, with a cage or ring for
      uncontained defects. Of the 50 previous revisions, 41 cages and nine rings were
      used with allografts for 14 minor-column and 36 major-column defects. We
      routinely assessed the size of the acetabular bone defect at the time of revision
      and re-revision surgery. This allowed us to assess whether host bone stock was
      restored. We also assessed the outcome of re-revision surgery in these
      circumstances by means of radiological characteristics, rates of failure and
      modes of failure. We subsequently investigated the factors that may affect the
      potential for the restoration of bone stock and the durability of the re-revision
      reconstruction using multivariate analysis. At the time of re-revision, there
      were ten host acetabula with no significant defects, 14 with contained defects,
      nine with minor-column, seven with major-column defects and ten with pelvic
      discontinuity. When bone defects at re-revision were compared with those at the
      previous revision, there was restoration of bone stock in 31 hips, deterioration
      of bone stock in nine and remained unchanged in ten. This was a significant
      improvement (p < 0.001). Morselised allografting at the index revision was not
      associated with the restoration of bone stock. In 17 hips (34%), re-revision was
      possible using a simple acetabular component without allograft, augments, rings
      or cages. There were 47 patients with a mean follow-up of 70 months (6 to 146)
      available for survival analysis. Within this group, the successful cases had a
      minimum follow-up of two years after re-revision. There were 22 clinical or
      radiological failures (46.7%), 18 of which were due to aseptic loosening. The
      five and ten year Kaplan-Meier survival rate was 75% (95% CI, 60 to 86) and 56%
      (95% CI, 40 to 70) respectively with aseptic loosening as the endpoint. The rate
      of aseptic loosening was higher for hips with pelvic discontinuity (p = 0.049)
      and less when the allograft had been in place for longer periods (p = 0.040). The
      use of a cage or ring over structural allograft bone for massive uncontained
      defects in acetabular revision can restore host bone stock and facilitate
      subsequent re-revision surgery to a certain extent.

PMID- 24589786
TI  - The anterolateral ligament: Anatomy, length changes and association with the
      Segond fracture.
AB  - There have been differing descriptions of the anterolateral structures of the
      knee, and not all have been named or described clearly. The aim of this study was
      to provide a clear anatomical interpretation of these structures. We dissected 40
      fresh-frozen cadaveric knees to view the relevant anatomy and identified a
      consistent structure in 33 knees (83%); we termed this the anterolateral ligament
      of the knee. This structure passes antero-distally from an attachment proximal
      and posterior to the lateral femoral epicondyle to the margin of the lateral
      tibial plateau, approximately midway between Gerdy's tubercle and the head of the
      fibula. The ligament is superficial to the lateral (fibular) collateral ligament
      proximally, from which it is distinct, and separate from the capsule of the knee.
      In the eight knees in which it was measured, we observed that the ligament was
      isometric from 0 degrees  to 60 degrees  of flexion of the knee, then slackened
      when the knee flexed further to 90 degrees  and was lengthened by imposing tibial
      internal rotation.

PMID- 24589787
TI  - Development of a patient-reported outcome measure of activity and participation
      (the OKS-APQ) to supplement the Oxford knee score.
AB  - The primary aim of this study was to develop a patient-reported Activity &
      Participation Questionnaire (the OKS-APQ) to supplement the Oxford knee score, in
      order to assess higher levels of activity and participation. The generation of
      items for the questionnaire involved interviews with 26 patients. Psychometric
      analysis (exploratory and confirmatory factor analysis and Rasch analysis) guided
      the reduction of items and the generation of a scale within a prospective study
      of 122 relatively young patients (mean age 61.5 years (42 to 71)) prior to knee
      replacement. A total of 99, completed pre-operative and six month post-operative
      assessments (new items, OKS, Short-Form 36 and American Knee Society Score). The
      eight-item OKS-APQ scale is unidimensional, reliable (Cronbach's alpha 0.85;
      intraclass correlation coefficient (ICC) 0.79; or 0.92 when one outlier was
      excluded), valid (r > 0.5 with related scales) and responsive (effect size 4.16).
      We recommend that it is used with the OKS with adults of all ages when further
      detail regarding the levels of activity and participation of a patient is
      required.

PMID- 24589788
TI  - Five- to ten-year outcome following medial opening-wedge high tibial osteotomy
      with rigid plate fixation in combination with an artificial bone substitute.
AB  - Between 2003 and 2007, 99 knees in 77 patients underwent opening wedge high
      tibial osteotomy. We evaluated the effect of initial stable fixation combined
      with an artificial bone substitute on the mid- to long-term outcome after medial
      opening-wedge high tibial osteotomy (HTO) for medial compartmental osteoarthritis
      or spontaneous osteonecrosis of the knee in 78 knees in 64 patients available for
      review at a minimum of five years (mean age 68 years; 49 to 82). The mean follow
      up was 6.5 years (5 to 10). The mean Knee Society knee score and function score
      improved from 49.6 (SD 11.4, 26 to 72) and 56.6 (SD 15.6, 5 to 100) before
      surgery to 88.1 (SD 12.5, 14 to 100) and 89.4 (SD 15.6, 5 to 100) at final follow
      up (p < 0.001) respectively. There were no significant differences between
      patients aged >= 70 and < 70 years. The mean standing femorotibial angle was
      corrected significantly from 181.7 degrees  (SD 2.7 degrees , 175 degrees  to 185
      degrees ) pre-operatively to 169.7 degrees  (SD 2.4 degrees , 164 degrees  to 175
      degrees ) at one year's follow-up (p < 0.001) and 169.6 degrees  (SD 3.0 degrees
      , 157 degrees  to 179 degrees ) at the final follow-up (p = 0.69 vs one year).
      Opening-wedge HTO using a stable plate fixation system combined with a bone
      substitute is a reliable procedure that provides excellent results. Although this
      treatment might seem challenging for older patients, our results strongly suggest
      that the results are equally good.

PMID- 24589789
TI  - Valgus subsidence of the tibial component in cementless Oxford unicompartmental
      knee replacement.
AB  - The cementless Oxford unicompartmental knee replacement has been demonstrated to
      have superior fixation on radiographs and a similar early complication rate
      compared with the cemented version. However, a small number of cases have come to
      our attention where, after an apparently successful procedure, the tibial
      component subsides into a valgus position with an increased posterior slope,
      before becoming well-fixed. We present the clinical and radiological findings of
      these six patients and describe their natural history and the likely causes. Two
      underwent revision in the early post-operative period, and in four the implant
      stabilised and became well-fixed radiologically with a good functional outcome.
      This situation appears to be avoidable by minor modifications to the operative
      technique, and it appears that it can be treated conservatively in most patients.

PMID- 24589790
TI  - An epidemiological study of rotator cuff pathology using The Health Improvement
      Network database.
AB  - Little is known about the incidence of rotator cuff pathology or its demographic
      associations in the general population. We undertook a large epidemiological
      study of rotator cuff pathology in the United Kingdom using The Health
      Improvement Network (THIN) database. The incidence of rotator cuff pathology was
      87 per 100,000 person-years. It was more common in women than in men (90 cases
      per 100,000 person-years in women and 83 per 100,000 person-years in men; p <
      0.001). The highest incidence of 198 per 100,000 person-years was found in those
      aged between 55 and 59 years. The regional distribution of incidence demonstrated
      an even spread across 13 UK health authorities except Wales, where the incidence
      was significantly higher (122 per 100,000 person-years; p < 0.001). The lowest
      socioeconomic group had the highest incidence (98 per 100,000 person-years). The
      incidence has risen fourfold since 1987 and as of 2006 shows no signs of
      plateauing. This study represents the largest general population study of rotator
      cuff pathology reported to date. The results obtained provide an enhanced
      appreciation of the epidemiology of rotator cuff pathology and may help to direct
      future upper limb orthopaedic services.

PMID- 24589791
TI  - Anterior dislocation of the shoulder in skeletally immature patients: comparison
      between non-operative treatment versus open Latarjet's procedure.
AB  - The ideal treatment for traumatic anterior dislocation of the shoulder in the
      skeletally immature patient is controversial. The aim of this study is to
      evaluate the outcomes after either conservative and/or surgical treatment using
      the Latarjet technique. A retrospective series of 49 out of 80 patients were
      reviewed. We found no significant differences between either treatment method
      regarding functional scores and pain levels. Although not statistically
      significant, post-surgical patients showed better signs of shoulder stability
      than others who have a higher rate of recurrence. Further, 92% of the post
      surgical group had returned to the same level of activity versus 52% in the non
      surgically treated group. We found no contraindications to operate on a
      skeletally immature patient.

PMID- 24589792
TI  - Decision making regarding spinal osteotomy and total hip replacement for
      ankylosing spondylitis: experience with 28 patients.
AB  - Few studies have examined the order in which a spinal osteotomy and total hip
      replacement (THR) are to be performed for patients with ankylosing spondylitis.
      We have retrospectively reviewed 28 consecutive patients with ankylosing
      spondylitis who underwent both a spinal osteotomy and a THR from September 2004
      to November 2012. In the cohort 22 patients had a spinal osteotomy before a THR
      (group 1), and six patients had a THR before a spinal osteotomy (group 2). The
      mean duration of follow-up was 3.5 years (2 to 9). The spinal sagittal Cobb angle
      of the vertebral osteotomy segment was corrected from a pre-operative kyphosis
      angle of 32.4 (SD 15.5 degrees ) to a post-operative lordosis 29.6 (SD 11.2
      degrees ) (p < 0.001). Significant improvements in pain, function and range of
      movement were observed following THR. In group 2, two of six patients had an
      early anterior dislocation. The spinal osteotomy was performed two weeks after
      the THR. At follow-up, no hip has required revision in either group. Although
      this non-comparative study only involved a small number of patients, given our
      experience, we believe a spinal osteotomy should be performed prior to a THR,
      unless the deformity is so severe that the procedure cannot be performed.

PMID- 24589793
TI  - The spectrum of fractures in the elderly.
AB  - Fractures in patients aged >= 65 years constitute an increasing burden on health
      and social care and are associated with a high morbidity and mortality. There is
      little accurate information about the epidemiology of fractures in the elderly.
      We have analysed prospectively collected data on 4786 in- and out-patients who
      presented with a fracture over two one-year periods. Analysis shows that there
      are six patterns of the incidence of fractures in patients aged >= 65 years. In
      males six types of fracture increase in incidence after the age of 65 years and
      11 types increase in females aged over 65 years. Five types of fracture decrease
      in incidence after the age of 65 years. Multiple fractures increase in incidence
      in both males and females aged >= 65 years, as do fractures related to falls.
      Analysis of the incidence of fractures, together with life expectancy, shows that
      the probability of males and females aged >= 65 years having a fracture during
      the rest of their life is 18.5% and 52.0%, respectively. The equivalent figures
      for males and females aged >= 80 years are 13.3% and 34.8%, respectively.

PMID- 24589794
TI  - The weekend effect: short-term mortality following admission with a hip fracture.
AB  - We retrospectively reviewed 2989 consecutive patients with a mean age of 81 (21
      to 105) and a female to male ratio of 5:2 who were admitted to our hip fracture
      unit between July 2009 and February 2013. We compared weekday and weekend
      admission and weekday and weekend surgery 30-day mortality rates for hip
      fractures treated both surgically and conservatively. After adjusting for
      confounders, weekend admission was independently and significantly associated
      with a rise in 30-day mortality (odds ratio (OR) 1.4, 95% confidence interval
      (CI) 1.02 to 1.9; p = 0.039) for patients undergoing hip fracture surgery. There
      was no increase in mortality associated with weekend surgery (OR 1.2, 95% CI 0.8
      to 1.7; p = 0.39). All hip fracture patients, whether managed surgically or
      conservatively, were more likely to die as an inpatient when admitted at the
      weekend (OR 1.4, 95% CI 1.02 to 1.80; p = 0.032), despite our unit having a
      comparatively low overall inpatient mortality (8.7%). Hip fracture patients
      admitted over the weekend appear to have a greater risk of death despite having a
      consultant-led service.

PMID- 24589795
TI  - Delayed debridement of severe open fractures is associated with a higher rate of
      deep infection.
AB  - This study explores the relationship between delay to surgical debridement and
      deep infection in a series of 364 consecutive patients with 459 open fractures
      treated at an academic level one trauma hospital in North America. The mean delay
      to debridement for all fractures was 10.6 hours (0.6 to 111.5). There were 46
      deep infections (10%). There were no infections among the 55 Gustilo-Anderson
      grade I open fractures. Among the grade II and III injuries, a statistically
      significant increase in the rate of deep infection was found for each hour of
      delay (OR = 1.033: 95% CI 1.01 to 1.057). This relationship shows a linear
      increase of 3% per hour of delay. No distinct time cut-off points were
      identified. Deep infection was also associated with tibial fractures (OR = 2.44:
      95% CI 1.26 to 4.73), a higher Gustilo-Anderson grade (OR = 1.99: 95% CI 1.004 to
      3.954), and contamination of the fracture (OR = 3.12: 95% CI 1.36 to 7.36). These
      individual effects are additive, which suggests that delayed debridement will
      have a clinically significant detrimental effect on more severe open fractures.
      Delayed treatment appeared safe for grade 1 open fractures. However, when the
      negative prognostic factors of tibial site, high grade of fracture and/or
      contamination are present we recommend more urgent operative debridement.

PMID- 24589796
TI  - The influence of distal locking on the need for fibular plating in intramedullary
      nailing of distal metaphyseal tibiofibular fractures.
AB  - Using human cadaver specimens, we investigated the role of supplementary fibular
      plating in the treatment of distal tibial fractures using an intramedullary nail.
      Fibular plating is thought to improve stability in these situations, but has been
      reported to have increased soft-tissue complications and to impair union of the
      fracture. We proposed that multidirectional locking screws provide adequate
      stability, making additional fibular plating unnecessary. A distal tibiofibular
      osteotomy model performed on matched fresh-frozen lower limb specimens was
      stabilised with reamed nails using conventional biplanar distal locking (CDL) or
      multidirectional distal locking (MDL) options with and without fibular plating.
      Rotational stiffness was assessed under a constant axial force of 150 N and a
      superimposed torque of +/- 5 Nm. Total movement, and neutral zone and fracture
      gap movement were analysed. In the CDL group, fibular plating improved stiffness
      at the tibial fracture site, albeit to a small degree (p = 0.013). In the MDL
      group additional fibular plating did not increase the stiffness. The MDL nail
      without fibular plating was significantly more stable than the CDL nail with an
      additional fibular plate (p = 0.008). These findings suggest that additional
      fibular plating does not improve stability if a multidirectional distal locking
      intramedullary nail is used, and is therefore unnecessary if not needed to aid
      reduction.

PMID- 24589797
TI  - Is there any benefit in pre-operative urinary analysis before elective total
      joint replacement?
AB  - Whether patients with asymptomatic bacteriuria should be investigated and treated
      before elective hip and knee replacement is controversial, although it is a
      widespread practice. We conducted a prospective observational cohort study with
      urine analyses before surgery and three days post-operatively. Patients with
      symptomatic urinary infections or an indwelling catheter were excluded. Post
      discharge surveillance included questionnaires to patients and general
      practitioners at three months. Among 510 patients (309 women and 201 men), with a
      median age of 69 years (16 to 97) undergoing lower limb joint replacements (290
      hips and 220 knees), 182 (36%) had pre-operative asymptomatic bacteriuria, mostly
      due to Escherichia coli, and 181 (35%) had white cells in the urine. Most
      patients (95%) received a single intravenous peri-operative dose (1.5 g) of
      cefuroxime as prophylaxis. On the third post-operative day urinary analysis
      identified white cells in 99 samples (19%) and bacteriuria in 208 (41%).
      Pathogens in the cultures on the third post-operative day were different from
      those in the pre-operative samples in 260 patients (51%). Only 25 patients (5%)
      developed a symptomatic urinary infection during their stay or in a subsequent
      three-month follow-up period, and two thirds of organisms identified were
      unrelated to those found during the admission. All symptomatic infections were
      successfully treated with oral antibiotics with no perceived effect on the joint
      replacement. We conclude that testing and treating asymptomatic urinary tract
      colonisation before joint replacement is unnecessary.

PMID- 24589798
TI  - Antibiotic-related acute kidney injury in patients undergoing elective joint
      replacement.
AB  - The aim of this study was to determine if a change in antibiotic prophylaxis for
      routine hip and knee replacement was associated with an increased risk of acute
      renal impairment. We identified 238 patients (128 knees and 110 hips) who had
      received a single prophylactic dose of 1.5 g cefuroxime before joint replacement.
      We compared them with prospectively collected data from 254 patients (117 knees
      and 137 hips) who received a single prophylactic dose of 2 g flucloxacillin and a
      height- and gender-determined dose of gentamicin. The primary outcome measure was
      any new renal impairment as graded by clinically validated criteria. We
      identified four patients (1.69%) in the cefuroxime group who developed renal
      impairment. All four had mild impairment and all renal function was normal by the
      third post-operative day. The incidence of new-onset renal impairment was
      significantly higher in the flucloxacillin-and-gentamicin group at 9.45% (24
      patients) (p < 0.001). Three of these patients remained with acute renal
      impairment after a week, although the serum creatinine levels in all subsequently
      returned to normal.

PMID- 24589799
TI  - Reconstruction of the hemipelvis with a modular prosthesis after resection of a
      primary malignant peri-acetabular tumour involving the sacroiliac joint.
AB  - We report our early experience with the use of a new prosthesis, the Modular
      Hemipelvic Prosthesis II, for reconstruction of the hemipelvis after resection of
      a primary malignant peri-acetabular tumour involving the sacroiliac joint. We
      retrospectively reviewed the outcome of 17 patients who had undergone resection
      of a pelvic tumour and reconstruction with this prosthesis between July 2002 and
      July 2010. One patient had a type I+II+III+IV resection (ilium + peri-acetabulum
      + pubis/ischium + sacrum) and 16 had a type I+II+IV resection (ilium + acetabulum
      + sacrum). The outcome was assessed at a mean follow-up of 33 months (15 to 59).
      One patient was alive with disease, 11 were alive without disease and five had
      died of disease. The overall five-year survival rate was 62.4%. Six patients had
      a local recurrence. The mean Musculoskeletal Tumour Society score was 58% (33 to
      77). Deep infection occurred in two patients, problems with wound healing in five
      and dislocation in one. For patients with a primary malignant peri-acetabular
      sarcoma involving the sacroiliac joint, we believe that this new prosthesis is a
      viable option for reconstruction of the bony defect left following resection of
      the tumour. It results in a satisfactory functional outcome with an acceptable
      rate of complications.

PMID- 24589800
TI  - The medial approach for the treatment of children with developmental dysplasia of
      the hip.
AB  - The medial approach for the treatment of children with developmental dysplasia of
      the hip (DDH) in whom closed reduction has failed requires minimal access with
      negligible blood loss. In the United Kingdom, there is a preference for these
      children to be treated using an anterolateral approach after the appearance of
      the ossific nucleus. In this study we compared these two protocols, primarily for
      the risk of osteonecrosis. Data were gathered prospectively for protocols
      involving the medial approach (26 hips in 22 children) and the anterolateral
      approach (22 hips in 21 children) in children aged < 24 months at the time of
      surgery. Osteonecrosis of the femoral head was assessed with validated scores.
      The acetabular index (AI) and centre-edge angle (CEA) were also measured. The
      mean age of the children at the time of surgery was 11 months (3 to 24) for the
      medial approach group and 18 months (12 to 24) for the anterolateral group, and
      the combined mean follow-up was 70 months (26 to 228). Osteonecrosis of the
      femoral head was evident or asphericity predicted in three of 26 hips (12%) in
      the medial approach group and four of 22 (18%) in the anterolateral group (p =
      0.52). The mean improvement in AI was 8.8 degrees  (4 degrees  to 12 degrees )
      and 7.9 degrees  (6 degrees  to 10 degrees ), respectively, at two years post
      operatively (p = 0.18). There was no significant difference in CEA values of
      affected hips between the two groups. Children treated using an early medial
      approach did not have a higher risk of developing osteonecrosis at early to mid
      term follow-up than those treated using a delayed anterolateral approach. The
      rates of acetabular remodelling were similar for both protocols.

PMID- 24589801
TI  - The impact factor of a journal is a poor measure of the clinical relevance of its
      papers.
AB  - We evaluated the top 13 journals in trauma and orthopaedics by impact factor and
      looked at the longer-term effect regarding citations of their papers. All 4951
      papers published in these journals during 2007 and 2008 were reviewed and
      categorised by their type, subspecialty and super-specialty. All citations
      indexed through Google Scholar were reviewed to establish the rate of citation
      per paper at two, four and five years post-publication. The top five journals
      published a total of 1986 papers. Only three (0.15%) were on operative
      orthopaedic surgery and none were on trauma. Most (n = 1084, 54.5%) were about
      experimental basic science. Surgical papers had a lower rate of citation (2.18)
      at two years than basic science or clinical medical papers (4.68). However, by
      four years the rates were similar (26.57 for surgery, 30.35 for basic
      science/medical), which suggests that there is a considerable time lag before
      clinical surgical research has an impact. We conclude that high impact journals
      do not address clinical research in surgery and when they do, there is a delay
      before such papers are cited. We suggest that a rate of citation at five years
      post-publication might be a more appropriate indicator of importance for papers
      in our specialty.

PMID- 24589802
TI  - The orthopaedic aspects of mycetoma.
AB  - This article presents an overview of mycetoma and offers guidelines for
      orthopaedic surgeons who may be involved in the care of patients with this
      condition.

PMID- 24589803
TI  - The rate of symptomatic venous thromboembolism in patients undergoing elective
      Ilizarov surgery and the cost of chemical prophylaxis.
AB  - Recent recommendations by the National Institute for Health and Care Excellence
      (NICE) suggest that all patients undergoing elective orthopaedic surgery should
      be assessed for the risk of venous thromboembolism (VTE). Little is known about
      the incidence of symptomatic VTE after elective external fixation. We studied a
      consecutive series of adult patients who had undergone elective Ilizarov surgery
      without routine pharmacological prophylaxis to establish the incidence of
      symptomatic VTE. A review of a prospectively maintained database of consecutive
      patients who were treated between October 1998 and February 2011 identified 457
      frames in 442 adults whose mean age was 42.6 years (16.0 to 84.6). There were 425
      lower limb and 32 upper limb frames. The mean duration of treatment was 25.7
      weeks (1.6 to 85.3). According to NICE guidelines all the patients had at least
      one risk factor for VTE, 246 had two, 172 had three and 31 had four or more. One
      patient (0.23%) developed a pulmonary embolus after surgery and was later found
      to have an inherited thrombophilia. There were 27 deaths, all unrelated to VTE.
      The cost of providing VTE prophylaxis according to NICE guidelines in this group
      of patients would be L89 493.40 (L195.80 per patient) even if the cheapest
      recommended medication was used. The rate of symptomatic VTE after Ilizarov
      surgery was low despite using no pharmacological prophylaxis. This study leads us
      to question whether NICE guidelines are applicable to these patients.

PMID- 24589805
TI  - Cerebral sinus thrombosis in a 6-year-old boy after a minor head injury.
AB  - Posttraumatic cerebral sinus thrombosis is an uncommon disease in children that
      is rarely seen in the setting of a closed head injury. We report a 6-year-old boy
      who developed cerebral sinus thrombosis after an apparent minor head injury. The
      clinical presentation, neuroimaging findings, and treatment strategies are
      discussed. Serial neurological evaluation and close observation are important,
      and the decision for anticoagulation should be carefully considered with
      hematological consultants. 

PMID- 24589806
TI  - Surfactant for acute respiratory distress syndrome caused by near drowning in a
      newborn.
AB  - BACKGROUND: Near drowning is the term for survival after suffocation caused by
      submersion in water or another fluid. Pulmonary insufficiency may develop
      insidiously or suddenly because of near drowning. AIM: We want to present a
      newborn case of acute respiratory distress syndrome caused by near drowning.
      CASE: A 26-day-old boy was brought to the emergency department because of severe
      respiratory distress. Two hours before admission, the baby suddenly slipped out
      his mother's hands and fell in the bathtub full of water while bathing. After
      initial resuscitation, he was transferred to the neonatal intensive care unit for
      mechanical ventilation. PaO2/FIO2 ratio was 97, with SaO2 of 84%. Bilateral
      heterogeneous densities were seen on his chest x-ray film. The baby was
      considered to have acute respiratory distress syndrome. Antibiotics were given to
      prevent infection. Because conventional therapy failed to improve oxygenation, a
      single dose of surfactant was tested via an intubation cannula. Four hours later,
      poractant alfa (Curosurf) administered repeatedly at the same dosage because of
      hypoxemia (PaO2/FIO2 ratio, 124; SaO2, 88%). Oxygen saturation was increased to
      more than 90% in 24 hours, which was maintained for 3 days when we were able to
      wean him from mechanical ventilation. After 7 days, the x-ray film showed
      considerable clearing of shadows. He was discharged home on the 15th day after
      full recovery. CONCLUSIONS: This case report describes a rapid and persistent
      improvement after 2 doses of surfactant in acute respiratory distress syndrome
      with severe oxygenation failure caused by near drowning in a newborn.

PMID- 24589807
TI  - A boy with sudden headache.
AB  - Headache is a common presenting complaint in pediatric emergency departments. The
      goal of emergent evaluation is to identify those children with potentially life
      threatening conditions. We present the case of an adolescent boy presenting with
      headache and hypertension who was diagnosed with a catecholamine-secreting
      abdominal paraganglioma. Genetic testing eventually led to the diagnosis of SDHB
      related hereditary paraganglioma-pheochromocytoma syndrome. Alarm features ("red
      flags") in children presenting with headache are reviewed, as well as the main
      features of paragangliomas and the indications for genetic testing. 

PMID- 24589808
TI  - Status epilepticus, cardiac resuscitation, and posterior reversible
      encephalopathy syndrome after ingestion of viscous lidocaine: a plea for more
      childproof packaging of pharmaceuticals.
AB  - Ingestion of viscous lidocaine in children can lead to potentially lethal
      neurologic and cardiac effects. We report the case of a 2-year-old boy who
      developed posterior reversible encephalopathy syndrome 2 days after unobserved
      ingestion of about 500 mg viscous lidocaine (40 mg/kg of bodyweight). Initially,
      the child presented with convulsive status epilepticus and subsequent cardiac
      arrest necessitating cardiopulmonary resuscitation for eight minutes. After 2
      days of full recovery, the child presented with progressive disorientation,
      dizziness, and visual neglect. Lasting for 2 days, these symptoms finally
      disappeared completely. Combined with the findings on cerebral magnetic resonance
      imaging, this episode was interpreted as posterior reversible encephalopathy
      syndrome. Two weeks after the ingestion, no neurologic and visual abnormalities
      were found. Viscous lidocaine is prescribed routinely for dentition or other
      painful lesions in the oral cavity in children. Despite the potential
      hazardousness of the drug, packaging of viscous lidocaine is not childproof.
      Therefore, physicians have to instruct the parents carefully to minimize the risk
      of overuse or accidental ingestion. In general, the use of viscous lidocaine
      should be limited. 

PMID- 24589809
TI  - Giant omental hemorrhagic cyst presenting as acute hemorrhagic anemia in a 21
      month-old infant.
AB  - An omental cyst is a very rare pathology, especially in small infants. Children
      generally present with abdominal distention with or without a palpable mass. The
      mass may be huge, simulating ascites. The most common presentation in children is
      that of a small-bowel obstruction. The differential diagnosis includes intestinal
      duplication cyst, ovarian, choledochal, pancreatic, splenic, or renal cysts,
      hydronephrosis, cystic teratoma, hydatid cyst, and ascites. We describe the
      clinical presentation, imaging features, surgical treatment, and postoperative
      course of a 21-month-old female infant with a congenital giant omental cyst. This
      entity is extremely rare but should be included in the differential diagnosis in
      similar cases. 

PMID- 24589810
TI  - Alternative airways for the pediatric emergency department.
AB  - Securing the pediatric airway in the emergency setting is an uncommon event that
      is complicated by anatomic, physiologic, and environmental factors. Even more
      uncommonly, practitioners are faced with the added complication of a difficult
      airway, and the question of what alternatives to traditional endotracheal
      intubation are available and most useful may arise. Timely and effective
      intervention determines the patient's clinical outcome. The purpose of this
      review was to detail specific alternative airway management strategies and tools
      for use in the pediatric emergency department. 

PMID- 24589812
TI  - An acutely altered toddler.

PMID- 24589813
TI  - The use of alternate light sources in the clinical evaluation of child abuse and
      sexual assault.
AB  - Alternate light sources are devices that produce visible and invisible light at
      specific wavelengths to allow for enhanced visualization of fluorescent
      substances. These devices (which include Wood's lamp and blue light) are often
      used in forensics for evidence collection and can be quite useful to physicians
      in the medical evaluation of suspected physical or sexual assault. An
      understanding of the proper applications, as well as the limitations, of each
      alternate light source is imperative to correctly performing and interpreting
      medical evaluations in the emergency department. This review discusses the
      evidence from prospective trials in children and adults on the ability of
      specific alternate light sources to identify evidence of physical or sexual
      assault and also highlights some promising new technological adjuncts to
      alternate light sources that may allow for accurate dating of bruising. 

PMID- 24589814
TI  - Mobile and web-based education: delivering emergency department discharge and
      aftercare instructions.
AB  - Prior research has identified deficiencies in the standard process of providing
      instructions for care at discharge from the emergency department (ED). Patients
      typically receive a brief verbal instruction, along with preformatted written
      discharge documents. Studies have found that understanding and retention of such
      information by families are very poor, leading to nonadherence in follow-up care,
      unnecessary return visit to the ED, and poor health outcomes. The combination of
      systems factors (information content, delivery methods, and timing) and patient
      factors (health literacy, language proficiency, and cultural factors) contributes
      to the challenge of providing successful discharge communication. Internet and
      mobile devices provide a novel opportunity to better engage families in this
      process.Mobile health can address both system- and patient-level challenges. By
      incorporating images, animation, and full Web-based video content, more
      comprehensible content that is better suited for patients with lower health
      literacy and today's visual learners can be created. Information can also be
      delivered both synchronously and asynchronously, enabling the health care
      providers to deliver health education to the patients electronically to their
      home, where health care occurs. Furthermore, the providers can track information
      access by patients, customize content to the individual patients, and reach other
      caregivers who may not be present during the ED visit. Further research is needed
      to develop the systems and best practices for incorporating mobile health in the
      ED setting. 

PMID- 24589815
TI  - Ultrasound-guided intra-articular lidocaine block for reduction of anterior
      shoulder dislocation in the pediatric emergency department.
AB  - We report a case of successful reduction of an anterior shoulder dislocation
      after ultrasound-guided intra-articular lidocaine (IAL) block with subsequent
      sonographic confirmation of reduction. Current literature suggests that IAL can
      provide similar levels of analgesia as intravenous sedation, and IAL block is
      associated with lower complication rates and shorter emergency department stays.
      However, these studies may be limited by uncertainty about the accuracy of
      landmark-based glenohumeral injections. The use of beside ultrasound may improve
      the effectiveness of IAL block for reduction of anterior shoulder dislocation and
      provide a mechanism for immediate postreduction evaluation of the placement of
      the humeral head. 

PMID- 24589816
TI  - A 22-month-old male child with a painless arm mass presenting to the emergency
      department.

PMID- 24589817
TI  - ECGs in the ED.

PMID- 24589818
TI  - Intravenous access in children in the emergency department.

PMID- 24589819
TI  - Current procedural terminology; a primer.
AB  - In 1966, The American Medical Association (AMA) working with multiple major
      medical specialty societies developed an iterative coding system for describing
      medical procedures and services using uniform language, the Current Procedural
      Terminology (CPT) system. The current code set, CPT IV, forms the basis of
      reporting most of the services performed by healthcare providers, physicians and
      non-physicians as well as facilities allowing effective, reliable communication
      among physician and other providers, third parties and patients. This coding
      system and its maintenance has evolved significantly since its inception, and now
      goes well beyond its readily perceived role in reimbursement. Additional roles
      include administrative management, tracking new and investigational procedures,
      and evolving aspects of 'pay for performance'. The system also allows for local,
      regional and national utilization comparisons for medical education and research.
      Neurointerventional specialists use CPT category I codes regularly--for example,
      36,215 for first-order cerebrovascular angiography, 36,216 for second-order
      vessels, and 37,184 for acute stroke treatment by mechanical means. Additionally,
      physicians add relevant modifiers to the CPT codes, such as '-26' to indicate
      'professional charge only,' or '-59' to indicate a distinct procedural service
      performed on the same day.

PMID- 24589821
TI  - Dynamic oscillatory signatures of central neuropathic pain in spinal cord injury.
AB  - Central neuropathic pain (CNP) is believed to be accompanied by increased
      activation of the sensorimotor cortex. Our knowledge of this interaction is based
      mainly on functional magnetic resonance imaging studies, but there is little
      direct evidence on how these changes manifest in terms of dynamic neuronal
      activity. This study reports on the presence of transient electroencephalography
      (EEG)-based measures of brain activity during motor imagery in spinal cord
      injured patients with CNP. We analyzed dynamic EEG responses during imaginary
      movements of arms and legs in 3 groups of 10 volunteers each, comprising able
      bodied people, paraplegic patients with CNP (lower abdomen and legs), and
      paraplegic patients without CNP. Paraplegic patients with CNP had increased event
      related desynchronization in the theta, alpha, and beta bands (16-24 Hz) during
      imagination of movement of both nonpainful (arms) and painful limbs (legs).
      Compared to patients with CNP, paraplegics with no pain showed a much reduced
      power in relaxed state and reduced event-related desynchronization during
      imagination of movement. Understanding these complex dynamic, frequency-specific
      activations in CNP in the absence of nociceptive stimuli could inform the design
      of interventional therapies for patients with CNP and possibly further
      understanding of the mechanisms involved. PERSPECTIVE: This study compares the
      EEG activity of spinal cord-injured patients with CNP to that of spinal cord
      injured patients with no pain and also to that of able-bodied people. The study
      shows that the presence of CNP itself leads to frequency-specific EEG signatures
      that could be used to monitor CNP and inform neuromodulatory treatments of this
      type of pain.

PMID- 24589822
TI  - Optimising Mycobacterium tuberculosis detection in resource limited settings.
AB  - OBJECTIVES: The light-emitting diode (LED) fluorescence microscopy has made acid
      fast bacilli (AFB) detection faster and efficient although its optimal
      performance in resource-limited settings is still being studied. We assessed the
      optimal performances of light and fluorescence microscopy in routine conditions
      of a resource-limited setting and evaluated the digestion time for sputum samples
      for maximum yield of positive cultures. DESIGN: Cross-sectional study. SETTING:
      Facility-based involving samples of routine patients receiving tuberculosis
      treatment and care from the main tuberculosis case referral centre in northern
      Nigeria. PARTICIPANTS: The study included 450 sputum samples from 150 new
      patients with clinical diagnosis of pulmonary tuberculosis. METHODS: The 450
      samples were pooled into 150 specimens, examined independently with mercury
      vapour lamp (FM), LED CysCope (CY) and Primo Star iLED (PiLED) fluorescence
      microscopies, and with the Ziehl-Neelsen (ZN) microscopy to assess the
      performance of each technique compared with liquid culture. The cultured
      specimens were decontaminated with BD Mycoprep (4% NaOH-1% NLAC and 2.9% sodium
      citrate) for 10, 15 and 20 min before incubation in Mycobacterium growth
      incubator tube (MGIT) system and growth examined for acid-fast bacilli (AFB).
      RESULTS: Of the 150 specimens examined by direct microscopy: 44 (29%), 60 (40%),
      49 (33%) and 64 (43%) were AFB positive by ZN, FM, CY and iLED microscopy,
      respectively. Digestion of sputum samples for 10, 15 and 20 min yielded
      mycobacterial growth in 72 (48%), 81 (54%) and 68 (45%) of the digested samples,
      respectively, after incubation in the MGIT system. CONCLUSIONS: In routine
      laboratory conditions of a resource-limited setting, our study has demonstrated
      the superiority of fluorescence microscopy over the conventional ZN technique.
      Digestion of sputum samples for 15 min yielded more positive cultures.

PMID- 24589823
TI  - Trends in the prevalences of congenital anomalies and age at motherhood in a
      Southern European region: a population-based study.
AB  - OBJECTIVES: To estimate the prevalences of the main groups of congenital
      anomalies and to assess their trend over time. DESIGN: Population-based study of
      prevalences. SETTING: The Basque Country, Spain. PARTICIPANTS: All births and all
      congenital anomalies diagnosed prenatally, at birth or during the first year of
      age, in all hospitals of the country, from 1999 to 2008. MAIN OUTCOMES MEASURES:
      Total diagnosed prevalences and prevalences at birth of all chromosomal and non
      chromosomal anomalies, Down's syndrome, anomalies of the nervous system, urinary,
      limbs, digestive system and congenital heart defects. RESULTS: Mean age (SD) of
      women at childbirth and the proportion of them over 35 years of age shifted from
      32.1 (4.5) years, with 18.3% in 1999-2001, to 32.3 (4.7) years, with 23.9% in
      2006-2008. Between 1999 and 2008, 991 cases of chromosomal anomalies and 3090 of
      non-chromosomal anomalies were diagnosed, which yields, respectively, total
      prevalences of 5.20/00 and of 16.20/00. Among chromosomal anomalies, Down's
      syndrome is the most frequent (2.90/00). With marginal statistical significance,
      the results point at an increasing trend in total diagnosed chromosomal
      anomalies, but a decreasing one in prevalences at birth. Among non-chromosomal
      congenital anomalies, congenital heart defects are the most frequent (5.20/00)
      one. Rates of all non-chromosomal, urinary and limb anomalies grew during the
      study period, whereas those of congenital heart defects and anomalies of the
      digestive system did not change significantly. CONCLUSIONS: In the Basque
      Country, rates of chromosomal anomalies are higher than the overall estimated
      prevalence in European countries, and continue to increase slightly, which may be
      related to the rise in maternal age. Rates of non-chromosomal anomalies are
      within the European frequent range of values, and the increases observed need to
      be checked in the following years.

PMID- 24589824
TI  - Expectations and illness perceptions as predictors of benefit recipiency among
      workers with common mental disorders: secondary analysis from a randomised
      controlled trial.
AB  - OBJECTIVE: Common mental disorders (CMDs) are among the leading causes of sick
      leave, and more knowledge on factors related to work participation and return-to
      work (RTW) in CMDs is needed. The aim of this study was to investigate RTW
      expectations and illness perceptions as predictors of benefit recipiency in CMDs.
      DESIGN: Study participants were enrolled in a randomised controlled trial and
      reported CMDs as a main obstacle for work participation. Three prespecified
      subgroups were included: people at risk of going on sick leave, people on sick
      leave (>3 weeks) or people on long-term benefits. Baseline questionnaire data and
      registry data at baseline and 6 months were used to investigate predictors of
      benefit recipiency at 6-month follow-up. Benefit recipiency included sickness
      benefits, disability pension, work assessment allowance and unemployment
      benefits. RESULTS: In this study, uncertain and negative RTW-expectations were
      strong predictors of benefit recipiency at 6 months follow-up. Illness
      perceptions predicted benefit recipiency in the unadjusted model, but not in the
      fully adjusted model. In the subgroup on sick leave, uncertain and negative RTW
      expectations predicted benefit recipiency, while in the subgroup of people at
      risk of going on sick leave, negative RTW-expectations predicted benefit
      recipiency. In the subgroup on long-term benefits, only female gender predicted
      benefit recipiency. CONCLUSIONS: For people with CMDs, uncertain and negative RTW
      expectations predict later benefit recipiency, and expectations seem particularly
      important for those at risk of or on sick leave. For those at risk of sick leave,
      benefit recipiency at follow-up denoted a transition onto sick leave or long-term
      benefit, while those on sick leave had remained so or were receiving long-term
      benefits. Addressing RTW-expectations in occupational healthcare services or
      vocational rehabilitation might be beneficial in early stages or even prior to a
      sick leave episode. TRIAL REGISTRATION: http://www.clinicaltrials.gov,
      NCT01146730.

PMID- 24589825
TI  - A longitudinal general population-based study of job strain and risk for coronary
      heart disease and stroke in Swedish men.
AB  - OBJECTIVES: The aim was to investigate whether psychosocial stress based on the
      job-demand-control (JDC) model increased the risk for coronary heart disease
      (CHD) and stroke. SETTING: Swedish men. PARTICIPANTS: The Primary Prevention
      Study (PPS) comprises 6070 men born between 1915 and 1925 free from previous
      history of CHD and stroke at baseline (1974-1977). Psychosocial workplace
      exposure was assessed using a job-exposure matrix (JEM) for the JDC model based
      on occupation at baseline. The participants were followed from baseline
      examination, until death, until hospital discharge or until 75 years of age,
      whichever occurred first, using the Swedish national register on cause of death
      and the Swedish hospital discharge register for non-fatal and fatal stroke and
      CHD events. Cox regression models were used with stroke or CHD as the outcome,
      using JDC model and age as explanatory variables, as well as stratified models
      with regard to smoking, self-reported stress, socioeconomic status, obesity,
      hypertension and diabetes. PRIMARY AND SECONDARY OUTCOME MEASURES: Risk for
      stroke and CHD. RESULTS: There was an increased risk (HR) for CHD in relation to
      high strain (HR 1.31, 95% CI 1.01 to 1.70). The risk was further increased among
      ever-smokers and among blue-collar workers. There was a relation between low
      control and increased risk for CHD (HR 1.19, 95% CI 1.06 to 1.35). There was no
      increased risk for stroke in any of the JDC categories. CONCLUSIONS: Exposure to
      occupational psychosocial stress defined as job strain or low control increased
      the risk for CHD, especially among smokers and blue-collar workers. There was no
      increased risk for stroke in any of the JDC categories.

PMID- 24589826
TI  - The promise of recovery: narratives of hope among homeless individuals with
      mental illness participating in a Housing First randomised controlled trial in
      Toronto, Canada.
AB  - OBJECTIVES: Hope is widely embraced as an important factor in the recovery
      process. The role of housing in inspiring hope and facilitating recovery has been
      explored with homeless populations but is not well understood. This study
      explores perspectives on hopes for recovery and the role of housing on these
      hopes from the perspective of homeless adults experiencing mental illness
      participating in a multisite Housing First randomised controlled trial in Canada.
      The study draws on data from in-depth qualitative interviews with participants
      from the Toronto, Ontario site of the 'At Home/Chez Soi' Project. DESIGN: In
      depth interviews were conducted with a subsample of participants from a larger
      Housing First randomised controlled trial. SETTING: The research took place in
      Toronto, Canada. PARTICIPANTS: 60 participants in the larger trial (36 from the
      Housing First group and 24 from the Treatment as Usual group) took part in in
      depth interviews. METHOD: Participants for the in-depth interviews were
      purposively selected from the larger trial sample in Toronto and participated in
      an interview at the beginning of the study (baseline). Data from the baseline
      interviews were analysed using the constant comparative method derived from
      grounded theory methods. RESULTS: Participants' narratives show clear
      visualisation of goals for recovery, and emphasise that housing is an integral
      factor that can facilitate hope and support dimensions of recovery. However, some
      participants had difficulty adjusting to housing, and were concerned about
      feeling socially isolated, which could have negative implications for hopefulness
      and recovery. CONCLUSIONS: Housing First interventions should explicitly
      incorporate hope-inspiring, recovery-oriented approaches and support participants
      while adjusting to housing in order to sustain hopefulness.

PMID- 24589827
TI  - Validity of self-reported hysterectomy: a prospective cohort study within the UK
      Collaborative Trial of Ovarian Cancer Screening (UKCTOCS).
AB  - OBJECTIVE: To evaluate the validity of self-reported hysterectomy against the
      gold standard of uterine visualisation using pelvic ultrasound. DESIGN:
      Prospective cohort study. SETTING: UK Collaborative Trial of Ovarian Cancer
      Screening (UKCTOCS) based in 13 National Health Service (NHS) Trusts in England,
      Wales and Northern Ireland. PARTICIPANTS: Between April 2001 and October 2005, 48
      215 postmenopausal women aged 50-74 randomised to the ultrasound screening arm of
      UKCTOCS underwent the first (initial) scan on the trial. INTERVENTIONS: At
      recruitment, the women completed a recruitment questionnaire (RQ) which included
      previous hysterectomy. The sonographer asked each woman regarding previous
      hysterectomy (interview format, IF) prior to the scan. At the scan, in addition
      to ovarian morphology, endometrial thickness (ET)/endometrial abnormality were
      captured if the uterus was visualised at the scan. OUTCOME MEASURES: Self
      reported hysterectomy at RQ or IF was compared to ultrasound data on
      ET/endometrial abnormality (as surrogate uterine visualisation markers) on the
      first (initial) scan. RESULTS: Of 48 215 women, 3 had congenital uterine agenesis
      and 218 inconclusive results. The uterus was visualised in 39 121 women. 8871
      self-reported hysterectomy at RQ, 8641 at IF and 8487 at both. The uterus was
      visualised in 39 123, 39 353 and 38 969 women not self-reporting hysterectomy at
      RQ, IF or both. Validity, sensitivity, specificity, positive predictive value and
      negative predictive value of using RQ alone, IF or both RQ/IF were 99.6%, 98.9%,
      99.7%, 98.9% and 99.7%; 98.9%, 98.4%, 99.1%, 95.9% and 99.7%; 99.8%, 99.6%,
      99.9%, 99.4% and 99.9%, respectively. CONCLUSIONS: Self-reported hysterectomy is
      a highly accurate and valid source for studying long-term associations of
      hysterectomy with disease onset. TRIAL REGISTRATION: International Standard
      Randomised Controlled Trial Number (ISRCTN)-22488978.

PMID- 24589828
TI  - The COgnitive-Pulmonary Disease (COgnitive-PD) study: protocol of a longitudinal
      observational comparative study on neuropsychological functioning of patients
      with COPD.
AB  - INTRODUCTION: Intact cognitive functioning is necessary for patients with chronic
      obstructive pulmonary disease (COPD) to understand the value of healthy lifestyle
      guidelines, to make informed decisions and subsequently act on it. Nevertheless,
      brain abnormalities and cognitive impairment have been found in patients with
      COPD. To date, it remains unknown which cognitive domains are affected and what
      the possible consequences are of cognitive impairment. Therefore, objectives of
      the study described are to determine neuropsychological functioning in patients
      with COPD, and its influence on health status, daily functioning and pulmonary
      rehabilitation outcome. Furthermore, structural and functional brain
      abnormalities and the relationship with cognitive and daily functioning will be
      explored. METHODS AND ANALYSIS: A longitudinal observational comparative study
      will be performed in 183 patients with COPD referred for pulmonary rehabilitation
      and in 90 healthy control participants. Demographic and clinical characteristics,
      activities of daily living and knowledge about COPD will be assessed. Baseline
      cognitive functioning will be compared between patients and controls using a
      detailed neuropsychological testing battery. An MRI substudy will be performed to
      compare brain abnormalities between 35 patients with COPD with cognitive
      impairment and 35 patients with COPD without cognitive impairment. Patients will
      be recruited between November 2013 and November 2015. ETHICS AND DISSEMINATION:
      The study has been approved by the Medical Ethics Committee of the University
      Hospital Maastricht and Maastricht University (NL45127.068.13/METC 13-3-035) and
      is registered in the Dutch trial register. All participants will provide written
      informed consent and can withdraw from the study at any point in time. Assessment
      and home visit data material will be managed anonymously. The results obtained
      can be used to optimise patient-oriented treatment for cognitively impaired
      patients with COPD. The findings will be disseminated in international peer
      reviewed journals and through research conferences.

PMID- 24589829
TI  - Serum levels of preoperative alpha-fetoprotein and CA19-9 predict survival of
      hepatic carcinoma patients after liver transplantation.
AB  - OBJECTIVE: The aim of this study was to assess serum levels of presurgical alpha
      fetoprotein (AFP) and carbohydrate antigen 19-9 (CA19-9) as prognostic markers in
      patients with hepatic carcinoma after liver transplantation (LT). METHODS: A
      total of 226 patients were recruited for the analysis of serum AFP and CA19-9
      levels, on the basis of which the tumor marker type (TMT) was defined and
      evaluated for prognostic prediction. Overall survival (OS) and relapse-free
      survival (RFS) were analyzed using Kaplan-Meier curves, and univariate and
      multivariate Cox models. RESULTS: One-year and 5-year OS were 79.0 and 58.0%,
      respectively, whereas RFS were 70.3 and 62.2%, respectively, in this cohort of
      patients. There were six variables predicting both OS and RFS, including TMT,
      tumor size, number of tumor lesions, extrahepatic or vascular invasion, and
      histopathological grade. Among these, TMT, tumor size, and extrahepatic invasion
      were all independent predictors of OS and RFS among these patients. Further, on
      the basis of TMT, novel LT selection criteria for patients with hepatic
      carcinoma, which supplemented the Milan criteria, were adopted, because the
      patients within the Milan criteria (n=107) and those exceeding Milan but
      fulfilling the proposed criteria (n=30) had similar 5-year OS (77.8 vs. 79.3%,
      P=0.862) and RFS (85.5 vs. 75.1%, P=0.210) rates. CONCLUSION: The data from this
      study showed that serum levels of preoperative AFP and CA19-9 were able to
      predict survival of patients with hepatic carcinoma after LT. This study included
      novel criteria, adding serum AFP and CA19-9 levels to the selection criteria for
      LT eligibility of patients, in addition to the Milan criteria.

PMID- 24589830
TI  - Management of systolic blood pressure after endoscopic submucosal dissection is
      crucial for prevention of post-ESD gastric bleeding.
AB  - OBJECTIVE: Endoscopic submucosal dissection (ESD) is a useful technique for early
      gastric neoplasms without lymph node metastasis. However, a critical complication
      is unpredictable post-ESD bleeding. Some risk factors for post-ESD bleeding have
      been reported previously, although those risk factors have not directly
      contributed toward prevention of post-ESD bleeding. MATERIALS AND METHODS: We
      retrospectively identified 186 gastric neoplasms in 183 consecutive patients
      treated with ESD from 2005 to 2012 at Nagoya City University Hospital, and
      divided them into two groups on the basis of the presence or absence of post-ESD
      bleeding. RESULTS: Of the 186 lesions, eight lesions (4.2%) developed post-ESD
      bleeding. Univariate analysis identified hypertension (38.8% in nonbleeding vs.
      87.5% in bleeding; P=0.009) and depressed-type tumors (26.4% in nonbleeding vs.
      62.5% in bleeding; P=0.040) as significantly related to the incidence of post-ESD
      bleeding. On multivariate analysis, hypertension (odds ratio, 11.55; 95%
      confidence interval, 1.20-111.66; P=0.034) and depressed-type tumors (odds ratio,
      5.36; 95% confidence interval, 1.12-25.73; P=0.036) were independent risk factors
      for post-ESD bleeding. Systolic blood pressure (SBP) after ESD was significantly
      higher in the post-ESD bleeding group than in the post-ESD non-bleeding group
      (P=0.021), with the comorbidity of hypertension significantly correlating with
      SBP after ESD (rho=0.332, P<0.001). CONCLUSION: Control of SBP after ESD is
      important for the prevention of post-ESD bleeding because hypertension as a
      comorbidity, which is associated positively with SBP after ESD, is a significant
      risk factor for post-ESD bleeding.

PMID- 24589831
TI  - Support of academic synthetic chemistry using separation technologies from the
      pharmaceutical industry.
AB  - The use of state-of-the-art separation tools from the pharmaceutical industry for
      addressing intractable separation problems from academic synthetic chemistry is
      evaluated, showing fast and useful results for the resolution of complex
      mixtures, separation of closely related components, visualization of difficult to
      detect compounds and purification of synthetic intermediates. Some
      recommendations for potential near term deployment of separation tools within
      academia and the evolution of next generation separation technologies are
      discussed. 

PMID- 24589833
TI  - Texture-based medical image retrieval in compressed domain using compressive
      sensing.
AB  - Content-based image retrieval has gained considerable attention in today's
      scenario as a useful tool in many applications; texture is one of them. In this
      paper, we focus on texture-based image retrieval in compressed domain using
      compressive sensing with the help of DC coefficients. Medical imaging is one of
      the fields which have been affected most, as there had been huge size of image
      database and getting out the concerned image had been a daunting task.
      Considering this, in this paper we propose a new model of image retrieval process
      using compressive sampling, since it allows accurate recovery of image from far
      fewer samples of unknowns and it does not require a close relation of matching
      between sampling pattern and characteristic image structure with increase
      acquisition speed and enhanced image quality. 

PMID- 24589832
TI  - Multiple and distinct strategies of yeast SNAREs to confer the specificity of
      membrane fusion.
AB  - Trans-QabcR-SNARE pairing on opposing membranes is crucial for eukaryotic
      membrane fusion, but how selective pairs of Qabc- and R-SNARE proteins regulate
      membrane fusion specificity remains elusive. Here, we studied 14 purified full
      length SNAREs that function in yeast endoplasmic reticulum (ER)-Golgi, intra
      Golgi, endosomal, and vacuolar transport by comprehensively testing cis-QabcR
      SNARE assembly and fusogenicity of reconstituted SNARE proteoliposomes.
      Strikingly, the cognate ER-Golgi and intra-Golgi SNARE-complex assemblies were
      highly stringent, whereas endosomal and vacuolar SNAREs assembled rather
      promiscuously into the non-cognate mixed complexes. However, these patterns of
      cis-SNARE assemblies cannot solely explain their potency to be fusogenic via
      trans-SNARE pairing: Only the vacuolar 3Q-SNARE combination is fusogenic in the
      absence of additional components; endosomal SNARE-dependent fusogenicity requires
      membrane-tethering factors; and ER-Golgi SNAREs can be fusogenic by synergistic
      actions of tethering factors and the cognate Sec1/Munc18-family protein Sly1p.
      Thus, our findings uncover multiple and distinct strategies of SNAREs to directly
      mediate fusion specificity. 

PMID- 24589834
TI  - DNA-algorithm for timetable problem.
AB  - Using of DNA molecules for solving of NP-complete problems is discussed.
      Properties of DNA allow one to reduce the number of operations from exponential
      to polynomial. DNA-algorithm for solving of the timetable problem is suggested.
      The starting point is a set of classes, teachers and hours with some limitations.
      It is necessary to determine whether there is a timetable satisfying all
      limitations. The sets of classes, teachers and hours are coded by chains of
      nucleotides. After preparing of the input multi-set containing all possible
      timetables the filtering procedure should be made. It allows to exclude all
      illegal timetables. The filtering algorithm is suggested. An example is
      described. The analysis of the algorithm is made. 

PMID- 24589835
TI  - Identification of unique repeated patterns, location of mutation in DNA finger
      printing using artificial intelligence technique.
AB  - In genetic engineering, conventional techniques and algorithms employed by
      forensic scientists to assist in identification of individuals on the basis of
      their respective DNA profiles involves more complex computational steps and
      mathematical formulae, also the identification of location of mutation in a
      genomic sequence in laboratories is still an exigent task. This novel approach
      provides ability to solve the problems that do not have an algorithmic solution
      and the available solutions are also too complex to be found. The perfect blend
      made of bioinformatics and neural networks technique results in efficient DNA
      pattern analysis algorithm with utmost prediction accuracy. 

PMID- 24589836
TI  - A direct method for computing extreme value (Gumbel) parameters for gapped
      biological sequence alignments.
AB  - We develop a general method for computing extreme value distribution (Gumbel,
      1958) parameters for gapped alignments. Our approach uses mixture distribution
      theory to obtain associated BLOSUM matrices for gapped alignments, which in turn
      are used for determining significance of gapped alignment scores for pairs of
      biological sequences. We compare our results with parameters already obtained in
      the literature. 

PMID- 24589837
TI  - Real-time estimation and detection of non-linearity in bio-signals using wireless
      brain-computer interface.
AB  - In this paper, the work is mainly concentrated on removing non-linear parameters
      to make the physiological signals more linear and reducing the complexity of the
      signals. This paper discusses three different types of techniques that can be
      successfully utilised to remove non-linear parameters in EEG and ECG. (i)
      Transformation technique using Discrete Walsh-Hadamard Transform (DWHT); (ii)
      application of fuzzy logic control and (iii) building the Adaptive Neuro-Fuzzy
      Inference System (ANFIS) model for fuzzy. This work has been inspired by the need
      to arrive at an efficient, simple, accurate and quicker method for analysis of
      bio-signal. 

PMID- 24589838
TI  - Functional and structural analysis of mice TRPC6 with human analogue through
      homology modelling.
AB  - Homology models are increasingly used to determine structural and functional
      relationships of genes and proteins in biomedical research. In the current study,
      for the first time, we compared the TRPC6 gene in mouse and human. The protein
      encoded by this gene forms a receptor activated calcium channel in cell membrane.
      Defects in this gene have been implicated in a wide range of diseases including
      glioblastomas. To determine the structural similarities in mouse and human TRPC6,
      we used standard bioinformatics tools such as fold prediction to identify the
      protein 3D structure, sequence-structure comparison, and prediction of template
      and protein structure. We also used glioblastoma cell line U373MG and human
      glioblastoma tumour tissues to study the expression of TRPC6 in disease
      conditions to implicate this gene in pathological ailment. Based on the results
      we conclude that human TRPC6 contains 90% identity and 93% similarity with mouse
      TRPC6, suggesting that this protein is well conserved in these two species. These
      isoforms likely demonstrate similar mechanisms in regulating gene expression;
      thus TRPC6 studies in mice may be extrapolated to humans. 

PMID- 24589839
TI  - Understanding the importance of natural neuromotor strategy in upper extremity
      neuroprosthetic control.
AB  - A key challenge in upper extremity neuroprosthetics is variable levels of skill
      and inconsistent functional recovery. We examine the feasibility and benefits of
      using natural neuromotor strategies through the design and development of a proof
      of-concept model for a feed-forward upper extremity neuroprosthetic controller.
      Developed using Artificial Neural Networks, the model is able to extract and
      classify neural correlates of movement intention from multiple brain regions that
      correspond to functional movements. This is unique compared to contemporary
      controllers that record from limited physiological sources or require learning of
      new strategies. Functional MRI (fMRI) data from healthy subjects (N = 13) were
      used to develop the model, and a separate group (N = 4) of subjects were used for
      validation. Results indicate that the model is able to accurately (81%) predict
      hand movement strictly from the neural correlates of movement intention.
      Information from this study is applicable to the development of upper extremity
      technology aided interventions. 

PMID- 24589840
TI  - Ni-catalyzed asymmetric reductive allylation of aldehydes with allylic
      carbonates.
AB  - This work features first asymmetric Ni-catalyzed reductive coupling of allylic
      carbonates with aldehydes, which may proceed via allyl-Ni intermediates although
      Zn was used as the terminal reductant. Moderate to excellent enantiomeric excess
      was obtained with excellent functional group tolerance. 

PMID- 24589841
TI  - End-stage renal disease from human immunodeficiency virus-associated nephropathy
      in the United States, 2001 through 2010.

PMID- 24589842
TI  - IR-stimulated visible fluorescence in pink and brown diamond.
AB  - Irradiation of natural pink and brown diamond by middle-ultraviolet light (photon
      energy epsilon >= 4.1 eV ) is seen to induce anomalous fluorescence phenomena at
      N3 defect centres (structure N3-V). When diamonds primed in this fashion are
      subsequently exposed to infrared light (even with a delay of many hours), a
      transient burst of blue N3 fluorescence is observed. The dependence of this IR
      triggered fluorescence on pump wavelength and intensity suggest that this
      fluorescence phenomena is intrinsically related to pink diamond photochromism. An
      energy transfer process between N3 defects and other defect species can account
      for both the UV-induced fluorescence intensity changes, and the apparent optical
      upconversion of IR light. From this standpoint, we consider the implications of
      this N3 fluorescence behaviour for the current understanding of pink diamond
      photochromism kinetics. 

PMID- 24589843
TI  - [Individualized stem cell therapy].
AB  - Stem cells are attributed with having a great potential in regenerative medicine.
      Pluripotent stem cells are particularly interesting because they can be
      multiplied indefinitely and also differentiated under defined conditions.
      Currently, cardiomyocytes can be differentiated very effectively from pluripotent
      stem cells, making the former an attractive starting material for cardiac disease
      modeling in a culture dish (patient in a dish) and cell based-therapy in heart
      failure. The rapid biotechnological advances made in recent years now enable
      these concepts to be translated into clinical applications. 

PMID- 24589845
TI  - Desorption of hydrogen from light metal hydrides: concerted electronic
      rearrangement and role of H...H interactions.
AB  - A theoretical study of the desorption of hydrogen from rhombic Group 1 metal
      hydride dimers reveals a concerted reorganisation of the electron density for the
      M-H and H-H moieties as the reaction coordinate is traversed and a closed-shell
      H...H interaction evolves into a covalent H2 bond. The central role played by
      homopolar dihydrogen bonding in this process is revealed and analysed.

PMID- 24589844
TI  - Hypothalamic-mediated control of glucose balance in the presence and absence of
      insulin.
AB  - Diabetes afflicts hundreds of millions worldwide. People affected by type 1
      diabetes mellitus (T1DM; the insulin-deficient form of diabetes) or type 2
      diabetes mellitus (T2DM; the insulin-resistant form of diabetes) have
      significantly reduced life expectancy compared to normal individuals. This is due
      in part to the fact that (despite improvements) current anti-diabetic approaches
      are suboptimal. Indeed, severe morbidities (e.g.: cardiovascular disease,
      hypertension) are still too often associated with diabetes. Recent preclinical
      results indicate that different types of hypothalamic neurons are endowed with
      the ability to mediate the hyperglycemia-lowering action of the adipocyte-derived
      hormone leptin in an insulin-dependent and insulin-independent fashion. These
      results may pave the way for better anti-diabetic approaches and therefore
      positively impact on life expectancy of diabetic subjects. 

PMID- 24589846
TI  - Significance of occlusal force for dietary fibre and vitamin intakes in
      independently living 70-year-old Japanese: from SONIC Study.
AB  - OBJECTIVES: The number of teeth has frequently been used as an indicator of oral
      health in investigations of food intake; however, this measure does not represent
      the efficacy of the masticatory performance. Masticatory performance may be more
      important for food selection and avoidance than number of remaining teeth. The
      aim of this study was to investigate the association of occlusal force with
      habitual dietary intakes in independently living older Japanese. METHODS: The
      study population was 757 community-dwelling people aged 69-71 years old.
      Bilateral maximal occlusal force in the intercuspal position was measured with
      pressure-sensitive sheets. Removable denture wearers kept their dentures in place
      during the measurements. Dietary habits during the preceding month were assessed
      using a brief-type self-administered diet history questionnaire that measures
      consumption frequencies of selected food commonly consumed and calculates energy
      adjusted dietary intakes. Linear trends of food and nutrient intakes with
      decreasing occlusal force were tested after adjusting for gender and
      socioeconomic factors. RESULTS: After adjusting for socioeconomic status and the
      number of remaining teeth, decline of occlusal force was significantly associated
      with lower intakes of vegetables, vitamins A, C, B6, folate, and dietary fibre (P
      for trend<0.05). In contrast, number of teeth was significantly associated only
      with calcium and zinc, controlling for occlusal force. CONCLUSIONS: It is
      concluded that occlusal force was significantly associated with intakes of
      vitamins and dietary fibre rather than number of remaining teeth in independently
      living older Japanese.

PMID- 24589847
TI  - Dental pulp stem cells: state of the art and suggestions for a true translation
      of research into therapy.
AB  - OBJECTIVES: Stem cells have the ability to rescue and/or repair injured tissue.
      In humans, it is possible to isolate different types of stem cells from the body.
      Among these, dental pulp stem cells (DPSCs) are relatively easily obtainable and
      exhibit high plasticity and multipotential capabilities. In particular they
      represent a gold standard for neural-crest-derived bone reconstruction in humans
      and can be used for the repair of body defects in low-risk autologous therapeutic
      strategies. SOURCES: An electronic search was conducted on PubMed databases and
      supplemented with a manual study of relevant references. RESULTS: All research
      described in this review highlight that DPSCs are mesenchymal stem cells that
      could be used in clinical applications. Unfortunately, very few clinical trials
      have been reported. Major obstacles imposed on researchers are hindering the
      translation of potentially effective therapies to the clinic. Both researchers
      and regulatory institutions need to develop a new approach to this problem,
      drawing up a new policy for good manufacturing practice (GMP) procedures. We
      strongly suggest that only general rules be standardized rather than everything.
      Importantly, this would not have an effect on the safety of patients, but may
      very well affect the results, which cannot be identical for all patients, due to
      physiological diversity in the biology of each patient. Alternatively, it would
      be important to study the role of specific molecules that recruit endogenous stem
      cells for tissue regeneration. In this way, the clinical use of stem cells could
      be successfully developed. CONCLUSIONS: DPSCs are mesenchymal stem cells that
      differentiate into different tissues, maintain their characteristics after
      cryopreservation, differentiate into bone-like tissues when loaded on scaffolds
      in animal models, and regenerate bone in human grafts. In summary, all data
      reported up to now should encourage the development of clinical procedures using
      DPSCs.

PMID- 24589848
TI  - A multi-centred clinical audit to describe the efficacy of direct supra-coronal
      splinting--a minimally invasive approach to the management of cracked tooth
      syndrome.
AB  - OBJECTIVES: This audit looked at the use of direct composite splinting to manage
      cracked tooth syndrome (CTS). METHODS: Patients who had been assessed as having
      CTS were offered the treatment of a directly bonded, composite overlay
      restoration placed in supra-occlusion. Cases were reviewed up to 3 months later.
      RESULTS: In all, 151 restorations were followed up in the audit of which 131 were
      successful at 3 months. The remaining 20 restorations failed due to pulp
      complications (11), failure of the composite (5) or intolerance to the high
      restoration (4). Of the 131, patients described transient problems with chewing
      (94), composite breakage (13), TMD (1), phonetics (1), increased mobility (1) and
      tender to chewing (1). CONCLUSIONS: This is a successful non-invasive method of
      managing CTS in the short term for patients willing to accept transient effects.

PMID- 24589850
TI  - Specialized adult congenital heart care saves lives.

PMID- 24589849
TI  - Hepatitis C virus core protein activates autophagy through EIF2AK3 and ATF6 UPR
      pathway-mediated MAP1LC3B and ATG12 expression.
AB  - HCV infection induces autophagy, but how this occurs is unclear. Here, we report
      the induction of autophagy by the structural HCV core protein and subsequent
      endoplasmic reticular (ER) stress in Huh7 hepatoma cells. During ER stress, both
      the EIF2AK3 and ATF6 pathways of the unfolded protein response (UPR) were
      activated by HCV core protein. Then, these pathways upregulated transcription
      factors ATF4 and DDIT3. The ERN1-XBP1 pathway was not activated. Through ATF4 in
      the EIF2AK3 pathway, the autophagy gene ATG12 was upregulated. DDIT3 upregulated
      the transcription of autophagy gene MAP1LC3B (LC3B) by directly binding to the 
      253 to -99 base region of the LC3B promoter, contributing to the development of
      autophagy. Collectively, these data suggest not only a novel role for the HCV
      core protein in autophagy but also offer new insight into detailed molecular
      mechanisms with respect to HCV-induced autophagy, specifically how downstream UPR
      molecules regulate key autophagic gene expression.

PMID- 24589851
TI  - Specialized adult congenital heart disease care: the impact of policy on
      mortality.
AB  - BACKGROUND: Clinical guidelines recommend specialized care for adult congenital
      heart disease (ACHD) patients. In reality, few patients receive such dedicated
      care. We sought to examine the impact of specialized care on ACHD patient
      mortality. METHODS AND RESULTS: We examined referral rates to specialized ACHD
      centers and ACHD patient mortality rates between 1990 and 2005 in the population
      based Quebec Congenital Heart Disease database (n=71 467). This period covers
      several years before and after the publication of guidelines endorsing
      specialized care for ACHD patients. A time-series design, based on Joinpoint and
      Poisson regression analyses, was used to assess the changes in annual referral
      and patient mortality rates. The association between specialized ACHD care and
      all-cause mortality was assessed in both case-control and cohort studies. The
      time-series analysis demonstrated a significant increase in referral rates to
      specialized ACHD centers in 1997 (rate ratio, +7.4%; 95% confidence interval
      [CI], +6.6% to +8.2%). In parallel, a significant reduction in expected ACHD
      patient mortality was observed after year 2000 (rate ratio, -5.0%;95% CI, -10.8%
      to -0.8%). In exploratory post hoc cohort and case-control analyses, specialized
      ACHD care was independently associated with reduced mortality (hazard ratio,
      0.78; 95% CI, 0.65-0.94) and a reduced odds of death (adjusted odds ratio, 0.82;
      95% CI, 0.08-0.97), respectively. This effect was predominantly driven by
      patients with severe congenital heart disease (hazard ratio, 0.38; 95% CI, 0.22
      0.67). CONCLUSIONS: A significant increase in referrals to specialized ACHD
      centers followed the introduction of the clinical guidelines. Moreover, referral
      to specialized ACHD care was independently associated with a significant
      mortality reduction. Our findings support a model of specialized care for all
      ACHD patients.

PMID- 24589852
TI  - 2014 AHA/ACC Guideline for the Management of Patients With Valvular Heart
      Disease: executive summary: a report of the American College of
      Cardiology/American Heart Association Task Force on Practice Guidelines.

PMID- 24589853
TI  - 2014 AHA/ACC Guideline for the Management of Patients With Valvular Heart
      Disease: a report of the American College of Cardiology/American Heart
      Association Task Force on Practice Guidelines.

PMID- 24589854
TI  - Integration of polarization and chromatic cues in the insect sky compass.
AB  - Animals relying on a celestial compass for spatial orientation may use the
      position of the sun, the chromatic or intensity gradient of the sky, the
      polarization pattern of the sky, or a combination of these cues as compass
      signals. Behavioral experiments in bees and ants, indeed, showed that direct
      sunlight and sky polarization play a role in sky compass orientation, but the
      relative importance of these cues are species-specific. Intracellular recordings
      from polarization-sensitive interneurons in the desert locust and monarch
      butterfly suggest that inputs from different eye regions, including polarized
      light input through the dorsal rim area of the eye and chromatic/intensity
      gradient input from the main eye, are combined at the level of the medulla to
      create a robust compass signal. Conflicting input from the polarization and
      chromatic/intensity channel, resulting from eccentric receptive fields, is
      eliminated at the level of the anterior optic tubercle and central complex
      through internal compensation for changing solar elevations, which requires input
      from a circadian clock. Across several species, the central complex likely serves
      as an internal sky compass, combining E-vector information with other celestial
      cues. Descending neurons, likewise, respond both to zenithal polarization and to
      unpolarized cues in an azimuth-dependent way. 

PMID- 24589855
TI  - Apoptosis-associated tyrosine kinase 1 inhibits growth and migration and promotes
      apoptosis in melanoma.
AB  - Apoptosis-associated tyrosine kinase 1 (AATK1) was initially identified as a
      protein that was dramatically overexpressed during growth arrest and apoptosis of
      32Dcl myeloblastic leukemia cells. AATK is expressed in different regions of the
      brain and may have a role in normal nervous system development by its dual
      functions of enhancing apoptosis of mature granule cells and promoting terminal
      neuronal differentiation of developing neurons. However, its function in cancer
      has never been studied. Melanoma is a tumor composed of transformed cells within
      the melanocyte lineage deriving from the embryonic neural crest. It has been
      shown that developmental pathways in neural crest cells have a direct bearing on
      melanoma formation and human metastatic melanoma cells express a dedifferentiated
      phenotype. We found that the expression levels of AATK are lower in metastatic
      melanoma cell lines compared with primary melanoma cell lines and normal human
      melanocytes. We found that depletion of AATK mRNA in metastatic melanoma cell
      lines enhanced cell migration in cell line derived from metastatic melanomas.
      Overexpression of AATK inhibited cell proliferation, colony formation, and
      promoted apoptosis in melanoma cell lines derived from primary and metastatic
      melanomas. Signal transduction pathway analysis revealed that Src is involved in
      regulating AATK. Our results demonstrate for the first time that AATK inhibits
      cell proliferation, colony formation, and migration, and also promotes apoptosis
      in melanoma cells. 

PMID- 24589856
TI  - HIF-mediated metabolic switching in bladder outlet obstruction mitigates the
      relaxing effect of mitochondrial inhibition.
AB  - Prior work demonstrated increased levels of hypoxia-inducible factor-1alpha (HIF
      1alpha) in the bladder following outlet obstruction, associated with bladder
      growth and fibrosis. Here we hypothesized that HIF induction in outlet
      obstruction also switches energetic support of contraction from mitochondrial
      respiration to glycolysis. To address this hypothesis, we created infravesical
      outlet obstruction in female Sprague-Dawley rats and examined HIF induction and
      transcriptional activation. HIF-1alpha increased after 6 weeks of outlet
      obstruction as assessed by western blotting and yet transcription factor-binding
      site analysis indicated HIF activation already at 10 days of obstruction.
      Accumulation HIF-2alpha and of Arnt2 proteins were found at 10 days, providing an
      explanation for the lack of correlation between HIF-1alpha protein and
      transcriptional activation. HIF signature targets, including Slc2a1, Tpi1, Eno1
      and Ldha increased in obstructed compared with sham-operated bladders. The
      autophagy markers Bnip3 and LC3B-II were also increased at 6 week of obstruction,
      but electron microscopy did not support mitophagy. Mitochondria were, however,
      remodeled with increased expression of Cox4 compared with other markers. In
      keeping with a switch toward glycolytic support of contraction, we found that
      relaxation by the mitochondrial inhibitor cyanide was reduced in obstructed
      bladders. This was mimicked by organ culture with the HIF-inducer
      dimethyloxalylglycine, which also upregulated expression of Ldha. On the basis of
      these findings, we conclude that HIF activation in outlet obstruction involves
      mechanisms beyond the accumulation of HIF-1alpha protein and that it results in a
      switch of the energetic support of contraction to anaerobic glycolysis. This
      metabolic adaptation encompasses increased expression of glucose transporters and
      glycolytic enzymes combined with mitochondrial remodeling. Together, these
      changes uphold contractility when mitochondrial respiration is limited. 

PMID- 24589857
TI  - iLIR: A web resource for prediction of Atg8-family interacting proteins.
AB  - Macroautophagy was initially considered to be a nonselective process for bulk
      breakdown of cytosolic material. However, recent evidence points toward a
      selective mode of autophagy mediated by the so-called selective autophagy
      receptors (SARs). SARs act by recognizing and sorting diverse cargo substrates
      (e.g., proteins, organelles, pathogens) to the autophagic machinery. Known SARs
      are characterized by a short linear sequence motif (LIR-, LRS-, or AIM-motif)
      responsible for the interaction between SARs and proteins of the Atg8 family.
      Interestingly, many LIR-containing proteins (LIRCPs) are also involved in
      autophagosome formation and maturation and a few of them in regulating signaling
      pathways. Despite recent research efforts to experimentally identify LIRCPs, only
      a few dozen of this class of-often unrelated-proteins have been characterized so
      far using tedious cell biological, biochemical, and crystallographic approaches.
      The availability of an ever-increasing number of complete eukaryotic genomes
      provides a grand challenge for characterizing novel LIRCPs throughout the
      eukaryotes. Along these lines, we developed iLIR, a freely available web
      resource, which provides in silico tools for assisting the identification of
      novel LIRCPs. Given an amino acid sequence as input, iLIR searches for instances
      of short sequences compliant with a refined sensitive regular expression pattern
      of the extended LIR motif (xLIR-motif) and retrieves characterized protein
      domains from the SMART database for the query. Additionally, iLIR scores xLIRs
      against a custom position-specific scoring matrix (PSSM) and identifies
      potentially disordered subsequences with protein interaction potential
      overlapping with detected xLIR-motifs. Here we demonstrate that proteins
      satisfying these criteria make good LIRCP candidates for further experimental
      verification. Domain architecture is displayed in an informative graphic, and
      detailed results are also available in tabular form. We anticipate that iLIR will
      assist with elucidating the full complement of LIRCPs in eukaryotes. 

PMID- 24589858
TI  - Gene expression profiling and bioinformatics analysis of gastric carcinoma.
AB  - Gastric cancer remains one of the major health problems worldwide, and it is one
      of the most common cancers and the leading cause of cancer-related deaths in
      China. This study was to analyze the expression profiles of genes in gastric
      carcinoma, and predict potential regulating factors. The gene expression profile
      data GSE13911 was downloaded from Gene Expression Omnibus and the differentially
      expressed genes (DEGs) were identified by t-test. Gene modules were constructed
      using hierarchical clustering in R based on average linkage and Pearson's
      correlation coefficient and functional analysis for these genes were performed
      with DAVID. Genes in each module with Pearson's correlation coefficient >0.3 were
      obtained to construct co-expression network. Protein-protein interactions (PPIs)
      were identified by comparing protein-protein interaction (PPI) network with co
      expression networks. In addition, the potential regulatory microRNAs and the
      transcription factors for each module were screened out. In this study, six
      modules associated with protein degradation, cell cycle, protein trafficking and
      immunoreaction were identified. COPS5 (COP9 Subunit 5) was the core protein in
      the largest PPI network of module 1. The transcription factors MYC and MAZ (Myc
      associated zinc-finger protein) were enriched in module 1. A total of 9 microRNA
      target bi-clusters were identified and module 1 enriched 20 genes targeting to
      miR-17-92 gene cluster(miR-17/20ab)and miR-106b-25 gene cluster (miR-106b/93). In
      conclusion, we constructed 6 gene modules and screened out some genes,
      transcriptional factors and microRNAs that may be used as potential molecular
      biomarkers for gastric carcinoma. 

PMID- 24589859
TI  - The PAS positive material in gastric cancer cells of signet ring type is not
      mucin.
AB  - PURPOSE: The purpose of this study is to assess the exocrine and neuroendocrine
      properties of tumour cells in diffuse gastric cancer with signet ring cell
      differentiation. MATERIAL AND METHODS: Mucin mRNA and protein expressions (MUC1,
      2, 3, 4, 5AC, 6 and MUC13) were assessed by immunohistochemistry and in situ
      hybridization. The neuroendocrine properties were evaluated by protein and mRNA
      expression of the general neuroendocrine markers chromogranin A and
      synaptophysin. RESULTS: No MUC expression was observed in signet ring tumour
      cells including the amorphous substance in any of the nine cases. All cases
      showed immunoreactivity to synaptophysin, and seven out of nine cases
      immunoreactivity to chromogranin A in signet ring and non-signet ring tumour
      cells. Chromogranin A mRNA expression was observed in tumour cells in all samples
      with retained mRNA. CONCLUSIONS: The lack of MUC protein and mRNA in signet ring
      tumour cells suggests the amorphous substance is not mucin. The lack of MUC mRNA
      expression in non-signet ring tumour cells questions exocrine differentiation in
      this tumour group. The abundant protein expression of the general neuroendocrine
      markers CgA and synaptophysin, and mRNA expression in tumour cells strengthens
      the hypothesis that this tumour group may be of neuroendocrine origin.

PMID- 24589860
TI  - Toward the ideal synthesis and molecular function through synthesis-informed
      design.
AB  - This Highlight describes factors that contribute to an ideal synthesis, including
      economies (step, time, atom, solvent, energy) and orientations (target,
      diversity, safety, function), and the role of synthesis-informed design directed
      at function in advancing synthesis and its impact on science. 

PMID- 24589861
TI  - Fluorometric sensing of Hg2+ ions in aqueous medium by nano-aggregates of a
      tripodal receptor.
AB  - Two new tripodal receptors (1-2) have been synthesized and characterized by
      various spectroscopic techniques. The nano-aggregates of 1 and 2 (N1 and N2) have
      been prepared by a re-precipitation method in aqueous medium and have shown
      different photo-physical properties. Nano-aggregates of 1 (N1) can selectively
      recognize Hg(2+) in aqueous medium in the presence of other metal ions with
      enhancement in fluorescent intensity. The response was linearly proportional to
      the concentration of Hg(2+) in the range 0-10 MUM with a detection limit of 2.4
      nM. The mechanism of selective binding of Hg(2+) by N1 has also been supported by
      theoretical studies. To the best of our knowledge, this work represents the first
      report on substituted thiourea based nano-aggregates for nano-molar detection of
      mercury in aqueous medium.

PMID- 24589862
TI  - Genetic analysis of TOR complex gene variation with human longevity: a nested
      case-control study of American men of Japanese ancestry.
AB  - The mechanistic target of rapamycin (mTOR) pathway is crucial for life span
      determination in model organisms. The aim of the present study was to test
      tagging single-nucleotide polymorphisms that captured most of the genetic
      variation across key TOR complex 1 (TORC1) and TOR complex 2 (TORC2) genes MTOR,
      RPTOR, and RICTOR and the important downstream effector gene RPS6KA1 for
      association with human longevity (defined as attainment of at least 95 years of
      age) as well as health span phenotypes. Subjects comprised a homogeneous
      population of American men of Japanese ancestry, well characterized for aging
      phenotypes and who have been followed for 48 years. The study used a nested case
      control design involving 440 subjects aged 95 years and older and 374 controls.
      It found no association of 6 tagging single-nucleotide polymorphisms for MTOR, 61
      for RPTOR, 7 for RICTOR, or 5 for RPS6KA1 with longevity. Of 40 aging-related
      phenotypes, no significant association with genotype was seen. Thus common
      genetic variation (minor allele frequency >=10%) in MTOR, RPTOR, RICTOR, and
      RPS6KA1 is not associated with extreme old age or aging phenotypes in this
      population. Further research is needed to assess the potential genetic
      contribution of other mTOR pathway genes to human longevity, gene expression,
      upstream and downstream targets, and clinically relevant aging phenotypes. 

PMID- 24589864
TI  - Abstracts: Pulse: a report on the UHC Annual Conference 2013, October 17-18,
      Atlanta, GA.

PMID- 24589863
TI  - Nutritional risk and body mass index predict hospitalization, nursing home
      admissions, and mortality in community-dwelling older adults: results from the
      UAB Study of Aging with 8.5 years of follow-up.
AB  - BACKGROUND: Nutritional risk and low BMI are common among community-dwelling
      older adults, but it is unclear what associations these factors have with health
      services utilization and mortality over long-term follow-up. The aim of this
      study was to assess prospective associations of nutritional risk and BMI with all
      cause, nonsurgical, and surgical hospitalization; nursing home admission; and
      mortality over 8.5 years. METHODS: Data are from 1,000 participants in the
      University of Alabama at Birmingham Study of Aging, a longitudinal, observational
      study of older black and white residents of Alabama aged 65 and older.
      Nutritional risk was assessed using questions associated with the DETERMINE
      checklist. BMI was categorized as underweight (<18.5), normal weight (18.5-24.9),
      overweight (25.0-29.9), class I obese (30.0-34.9), and classes II and III obese
      (>=35.0). Cox proportional hazards models were fit to assess risk of all-cause,
      nonsurgical, and surgical hospitalization; nursing home admission; and mortality.
      Covariates included social support, social isolation, comorbidities, and
      demographic measures. RESULTS: In adjusted models, persons with high nutritional
      risk had 51% greater risk of all-cause hospitalization (95% confidence interval:
      1.14-2.00) and 50% greater risk of nonsurgical hospitalizations (95% confidence
      interval: 1.11-2.01; referent: low nutritional risk). Persons with moderate
      nutritional risk had 54% greater risk of death (95% confidence interval: 1.19
      1.99). BMI was not associated with any outcomes in adjusted models. CONCLUSIONS:
      Nutritional risk was associated with all-cause hospitalizations, nonsurgical
      hospitalizations, and mortality. Nutritional risk may affect the disablement
      process that leads to health services utilization and death. These findings point
      to the need for more attention on nutritional assessment, interventions, and
      services for community-dwelling older adults.

PMID- 24589865
TI  - Assessment of post-operative pain in cats: a case study on veterinary students of
      Universiti Putra Malaysia.
AB  - The ability to assess and control pain is listed as one of the desired Day One
      competencies among veterinary graduates. As such, a study was conducted to
      examine the current status and effectiveness of a video-based training module on
      the attitude toward and knowledge of pain assessment in cats among fourth- and
      final-year veterinary students of Universiti Putra Malaysia (UPM) in January of
      2013. A total of 92 students participated in this study, resulting in a response
      rate of 60.1%. Upon completion of a pre-training survey, the respondents
      undertook an interactive video-based presentation, followed by a post-training
      survey. The majority of the students (96.7%) agreed on the importance of pain
      management. Before the training, many (76.1%) disagreed that they had received
      adequate training, while 53.3% were not confident in their pain-recognition
      skills. After training, their knowledge and confidence in pain assessment
      increased. Responses to the survey were not associated with differences in
      gender, level of study, or field of interest. Students were found to have
      mistaken some physiologic parameters as good pain indicators after
      ovariohysterectomy. Their assessment of three standardized video cases revealed
      that they could recognize prominent signs of pain but failed to identify changes
      in behavior that were more subtle. Refinement to the training module is required
      to address the above deficiencies. 

PMID- 24589866
TI  - Teacher development: a patchwork-text approach to enhancing critical reflection
      in veterinary and para-veterinary educators.
AB  - Reflection is an essential component of teacher-development programs, and
      reliable, valid methods to teach, assess, and evaluate reflection are critical.
      However, it is important that appropriate methods are created for and evaluated
      across multiple disciplinary backgrounds, as the participants' backgrounds are a
      major factor in the development of critical reflection. The patchwork-text
      approach is a narrative process that is predominantly focused on the personal
      development of the individual. The current study used the patchwork-text approach
      for the development of reflection in participants with a science background who
      had not used a reflective approach for personal development before. Twenty
      summative essays and 103 formative essays from 21 participants who underwent a 1
      year higher-education teacher-development program were analyzed to assess whether
      the quality and quantity of reflective writing was enhanced through a regular,
      iterative process of reflective writing with feedback. The analysis of the essays
      involved the use of a predefined set of criteria for identifying the different
      reflective levels from 1 to 4 and the calculation of a reflective score to
      evaluate the overall development. The results show a clear improvement of higher
      level critical thinking as the participants progressed through their course.
      Higher levels of reflection were achieved particularly where a unit focused on a
      familiar area for the participant as opposed to one in which the participant had
      less experience. The analysis provides evidence that the patchwork text is a
      useful method for development and evaluation of reflection in participants with a
      veterinary/animal-science base. 

PMID- 24589868
TI  - II. Looking into the future of platelet transfusion in the presence of P2Y(12)
      inhibitors.

PMID- 24589867
TI  - PQ segment depression in patients with short QT syndrome: a novel marker for
      diagnosing short QT syndrome?
AB  - BACKGROUND: Patients with short QT syndrome (SQTS) have an increased risk for
      atrial tachyarrhythmias, ventricular tachyarrhythmias, and/or sudden cardiac
      death. PQ segment depression (PQD) is related to atrial fibrillation and carries
      a poor prognosis in the setting of acute inferior myocardial infarction and is a
      well-defined electrocardiographic (ECG) marker of acute pericarditis. OBJECTIVE:
      To evaluate the prevalence of PQD in SQTS and to analyze the association with
      atrial arrhythmias. METHODS: Digitalized 12-lead ECGs of SQTS patients were
      evaluated for PQD in all leads and for QT intervals in leads II and V5. PQD was
      defined as >=0.05 mV (0.5 mm) depression from the isoelectric line. RESULTS: A
      total of 760 leads from 64 SQTS patients (mean age 36 +/- 18 years; 48 [75%] men)
      were analyzed. PQD was seen in 265 (35%) leads from 52 (81%) patients and was
      more frequent in leads II, V3, aVF, V4, and I (n = 43 [67%], n = 30 [47%], n = 27
      [42%], n = 25 [39%], and n = 25 [39%], respectively). Nine of 64 (14%) patients
      presented with atrial tachyarrhythmias, and all of them had PQD. CONCLUSION:
      Fifty-two of 64 (81%) patients with SQTS reveal PQD. As PQD is rarely observed in
      healthy individuals, this ECG stigma may constitute a novel marker for SQTS in
      addition to a short QT interval.

PMID- 24589869
TI  - Personality and alcohol-related outcomes among mandated college students:
      descriptive norms, injunctive norms, and college-related alcohol beliefs as
      mediators.
AB  - The present study examined three alcohol-perception variables (descriptive norms,
      injunctive norms, and college-related alcohol beliefs) as mediators of the
      predictive effects of four personality traits (impulsivity, sensation seeking,
      anxiety sensitivity, and hopelessness) on alcohol use and alcohol-related
      consequences in a sample of mandated college students (n=875). Our findings
      replicated several findings of a previous study of incoming freshman college
      students (Hustad et al., in press) in that impulsivity and hopelessness had
      direct effects on alcohol-related problems, sensation seeking and impulsivity had
      indirect effects on alcohol-related outcomes via college-related alcohol beliefs,
      and college-related alcohol beliefs predicted both alcohol use and alcohol
      related problems. We discuss the implications of our findings for global college
      student interventions as well as personality-targeted interventions. 

PMID- 24589870
TI  - Physical activity as a coping strategy for smoking cessation in mid-life and
      older adults.
AB  - Smoking prevalence for those ages 45-65 is higher than the national average and
      the number of mid-life and older smokers is expected to increase as baby boomers
      age. Cessation, even after age 65, confers health benefits. Both physiologic and
      psychological mechanisms support use of physical activity (PA) as a coping tool
      for quitting and improving health. This study focused on use of PA for coping
      with urges to smoke, factors associated with use, and whether use of PA was
      associated with abstinence at 12 months for 799 smokers ages 50 and older. Only
      11.6% used PA for coping, with walking the most common PA. Females were more
      likely to use PA relative to males. Though in the predicted direction, use of PA
      was not significantly associated with 12-month abstinence. Male gender and higher
      baseline self-efficacy to quit were associated with 12 month abstinence.
      Encouraging use of PA during smoking cessation does not impede quitting and may
      improve health outcomes. Further research on whether PA increases abstinence with
      a larger sample of mid-life and older adults is indicated.

PMID- 24589871
TI  - Parenting under the influence: the effects of opioids, alcohol and cocaine on
      mother-child interaction.
AB  - Nearly 20% of adults receiving treatment for a substance use disorder live with
      their minor children (Stanger et al., 1999) and women in drug use treatment are
      twice as likely as men to have children in their household (Wechsberg et al.,
      1998). Parental drug use impacts the family through reduced family resources such
      as money and food, and researchers consistently note parenting deficits among
      substance users (Solis, Shadur, Burns, & Hussong, 2012). Little is known about
      differences in parenting and mother-child interaction among mothers with
      different drugs of choice or among mothers of older children, between 8 and 16
      years. This study reports the findings from a sample of treatment seeking opioid,
      alcohol and cocaine using mothers and their 8-16-year-old child. Findings from a
      mother-child observational task and self-reported parenting measure indicated
      less undermining autonomy and higher mother maternal acceptance among opioid
      compared to alcohol addicted mothers. African American mothers were observed to
      have fewer negative interactional behaviors than Whites and both African American
      mothers and children self-reported higher firm control and maternal acceptance.
      Overall, mothers appeared to struggle with effective discipline with older versus
      younger children. Findings offer useful information to clinicians seeking to
      effectively tailor their interventions to women and children who present with
      different drugs of abuse, race/culture and developmental stage of child.

PMID- 24589873
TI  - High-risk use by patients prescribed opioids for pain and its role in overdose
      deaths.
AB  - IMPORTANCE: From January 1, 2003, through December 31, 2010, drug overdose deaths
      in Tennessee increased from 422 to 1059 per year. More of these deaths involved
      prescription opioids than heroin and cocaine combined. OBJECTIVE: To assess the
      contribution of certain opioid-prescribing patterns to the risk of overdose
      death. DESIGN, SETTING, AND PARTICIPANTS: We performed a matched case-control
      study that analyzed opioid prescription data from the Tennessee Controlled
      Substances Monitoring Program (TNCSMP) from January 1, 2007, through December 31,
      2011, to identify risk factors associated with opioid-related overdose deaths
      from January 1, 2009, through December 31, 2010. Case patients were ascertained
      from death certificate data. Age- and sex-matched controls were randomly selected
      from among live patients in the TNCSMP. MAIN OUTCOMES AND MEASURES: We defined a
      high-risk number of prescribers or pharmacies as 4 or more per year and high-risk
      dosage as a daily mean of more than 100 morphine milligram equivalents (MMEs) per
      year. The main outcome was opioid-related overdose death. RESULTS: From January
      1, 2007, through December 31, 2011, one-third of the population of Tennessee
      filled an opioid prescription each year, and opioid prescription rates increased
      from 108.3 to 142.5 per 100 population per year. Among all patients in Tennessee
      prescribed opioids during 2011, 7.6% used more than 4 prescribers, 2.5% used more
      than 4 pharmacies, and 2.8% had a mean daily dosage greater than 100 MMEs.
      Increased risk of opioid-related overdose death was associated with 4 or more
      prescribers (adjusted odds ratio [aOR], 6.5; 95% CI, 5.1-8.5), 4 or more
      pharmacies (aOR, 6.0; 95% CI, 4.4-8.3), and more than 100 MMEs (aOR, 11.2; 95%
      CI, 8.3-15.1). Persons with 1 or more risk factor accounted for 55% of all
      overdose deaths. CONCLUSIONS AND RELEVANCE: High-risk use of prescription opioids
      is frequent and increasing in Tennessee and is associated with increased overdose
      mortality. Use of prescription drug-monitoring program data to direct risk
      reduction measures to the types of patients overrepresented among overdose deaths
      might reduce mortality associated with opioid abuse.

PMID- 24589872
TI  - Long-term exposure to air pollution and cardiovascular mortality: an analysis of
      22 European cohorts.
AB  - BACKGROUND: Air pollution has been associated with cardiovascular mortality, but
      it remains unclear as to whether specific pollutants are related to specific
      cardiovascular causes of death. Within the multicenter European Study of Cohorts
      for Air Pollution Effects (ESCAPE), we investigated the associations of long-term
      exposure to several air pollutants with all cardiovascular disease (CVD)
      mortality, as well as with specific cardiovascular causes of death. METHODS: Data
      from 22 European cohort studies were used. Using a standardized protocol, study
      area-specific air pollution exposure at the residential address was characterized
      as annual average concentrations of the following: nitrogen oxides (NO2 and NOx);
      particles with diameters of less than 2.5 MUm (PM2.5), less than 10 MUm (PM10),
      and 10 MUm to 2.5 MUm (PMcoarse); PM2.5 absorbance estimated by land-use
      regression models; and traffic indicators. We applied cohort-specific Cox
      proportional hazards models using a standardized protocol. Random-effects meta
      analysis was used to obtain pooled effect estimates. RESULTS: The total study
      population consisted of 367,383 participants, with 9994 deaths from CVD
      (including 4,992 from ischemic heart disease, 2264 from myocardial infarction,
      and 2484 from cerebrovascular disease). All hazard ratios were approximately 1.0,
      except for particle mass and cerebrovascular disease mortality; for PM2.5, the
      hazard ratio was 1.21 (95% confidence interval = 0.87-1.69) per 5 MUg/m and for
      PM10, 1.22 (0.91-1.63) per 10 MUg/m. CONCLUSION: In a joint analysis of data from
      22 European cohorts, most hazard ratios for the association of air pollutants
      with mortality from overall CVD and with specific CVDs were approximately 1.0,
      with the exception of particulate mass and cerebrovascular disease mortality for
      which there was suggestive evidence for an association.

PMID- 24589874
TI  - Subretinal drusenoid deposits: further characterization by lipid histochemistry.

PMID- 24589875
TI  - Pars plana vitrectomy for vitreous floaters: is there such a thing as minimally
      invasive vitreoretinal surgery?

PMID- 24589876
TI  - A microfluidic chip with a U-shaped microstructure array for multicellular
      spheroid formation, culturing and analysis.
AB  - Multicellular spheroids (MCS), formed by self-assembly of single cells, are
      commonly used as a three-dimensional cell culture model to bridge the gap between
      in vitro monolayer culture and in vivo tissues. However, current methods for MCS
      generation and analysis still suffer drawbacks such as being labor-intensive and
      of poor controllability, and are not suitable for high-throughput applications.
      This study demonstrates a novel microfluidic chip to facilitate MCS formation,
      culturing and analysis. The chip contains an array of U-shaped microstructures
      fabricated by photopolymerizing the poly(ethylene glycol) diacrylate hydrogel
      through defining the ultraviolet light exposure pattern with a photomask. The
      geometry of the U-shaped microstructures allowed trapping cells into the pocket
      through the actions of fluid flow and the force of gravity. The hydrogel is non
      adherent for cells, promoting the formation of MCS. Its permselective property
      also facilitates exchange of nutrients and waste for MCS, while providing
      protection of MCS from shearing stress during the medium perfusion. Heterotypic
      MCS can be formed easily by manipulating the cell trapping steps. Subsequent drug
      susceptibility analysis and long-term culture could also be achieved within the
      same chip. This MCS formation and culture platform can be used as a micro-scale
      bioreactor and applied in many cell biology and drug testing studies. 

PMID- 24589877
TI  - Cluster mean-field theory study of J1-J2 Heisenberg model on a square lattice.
AB  - We study the spin-1/2 J1-J2 Heisenberg model on a square lattice using the
      cluster mean-field theory. We find a rapid convergence of phase boundaries with
      increasing cluster size. By extrapolating the cluster size L to infinity, we
      obtain accurate phase boundaries J(c1)(2) ~ 0.42 (between the Neel
      antiferromagnetic phase and non-magnetic phase), and J(c2)(2) ~ 0.59 (between non
      magnetic phase and the collinear antiferromagnetic phase). Our results support
      the second-order phase transition at J(c1)(2) and the first-order one at
      J(c2)(2). For the spin-anisotropic J1-J2 model, we present its finite temperature
      phase diagram and demonstrate that the non-magnetic state is unstable towards the
      first-order phase transition under intermediate spin anisotropy.

PMID- 24589878
TI  - Complementarity of reaction force and electron localization function analyses of
      asynchronicity in bond formation in Diels-Alder reactions.
AB  - We have computationally compared three Diels-Alder cycloadditions involving
      cyclopentadiene and substituted ethylenes; one of the reactions is synchronous,
      while the others are slightly or highly asynchronous. Synchronicity and weak
      asynchronicity are characterized by the reaction force constant kappa(xi) having
      just a single minimum in the transition region along the intrinsic reaction
      coordinate xi, while for high asynchronicity kappa(xi) has a negative maximum
      with minima on both sides. The electron localization function (ELF) shows that
      the features of kappa(xi) can be directly related to the formation of the new C-C
      bonds between the diene and the dienophile. There is thus a striking
      complementarity between kappa(xi) and ELF; kappa(xi) identifies the key points
      along xi and ELF describes what is happening at those points. 

PMID- 24589879
TI  - Efficient sample tracking with OpenLabFramework.
AB  - The advance of new technologies in biomedical research has led to a dramatic
      growth in experimental throughput. Projects therefore steadily grow in size and
      involve a larger number of researchers. Spreadsheets traditionally used are thus
      no longer suitable for keeping track of the vast amounts of samples created and
      need to be replaced with state-of-the-art laboratory information management
      systems. Such systems have been developed in large numbers, but they are often
      limited to specific research domains and types of data. One domain so far
      neglected is the management of libraries of vector clones and genetically
      engineered cell lines. OpenLabFramework is a newly developed web-application for
      sample tracking, particularly laid out to fill this gap, but with an open
      architecture allowing it to be extended for other biological materials and
      functional data. Its sample tracking mechanism is fully customizable and aids
      productivity further through support for mobile devices and barcoded labels. 

PMID- 24589880
TI  - The astrocyte marker Aldh1L1 does not reliably label enteric glial cells.
AB  - Enteric glial cells are increasingly acknowledged as important partners of
      enteric neurons in the control of gastrointestinal function. They share
      morphological features and expression of antigenic markers with astrocytes of the
      central nervous system. Recently, aldehyde dehydrogenase 1 family member L1
      (Aldh1L1) has been proposed as a novel and specific marker for astrocytes. Taking
      the known similarities between astrocytes and enteric glia into account, we
      sought to investigate whether enteric glial cells also express Aldh1L1. To this
      end, we performed immunostaining on preparations of myenteric plexus obtained
      from adult Aldh1L1-eGFP bacterial artificial chromosome (BAC) transgenic mice and
      found that the Aldh1L1 promoter is indeed active in enteric glia, albeit mainly
      in cells residing outside the myenteric ganglia. Apart from enteric glia, we also
      observed eGFP expression in interstitial cells of Cajal. Furthermore, myenteric
      ganglia of the large intestine contained eGFP positive neurons. Taken together,
      our data indicate that Aldh1L1 is not a suitable marker for enteric glial cells. 

PMID- 24589881
TI  - Effects of a selective serotonin reuptake inhibitor escitalopram on the cutaneous
      silent period: a randomized controlled study in healthy volunteers.
AB  - The cutaneous silent period (CSP) involves a transient inhibition of the
      electromyographic (EMG) activity in the hand muscles induced by a painful
      electrical stimulation of the digital nerves. The neurotransmitters potentially
      involved in mediating the CSP have not been completely elucidated thus far.
      However, few studies suggest that the monoaminergic system may play a role in the
      CSP. We elicited CSPs in the first dorsal interosseous muscle of the right hand
      before and 3h after administration of a single oral dose of the selective
      serotonin reuptake inhibitor escitalopram (20mg) or placebo. The two experimental
      sessions (drug and placebo) were performed in a random order at >=1-week
      intervals. All recordings were numbered anonymously and analysed offline in a
      blind manner by one investigator. A significant increase in the CSP duration was
      observed 3h after escitalopram administration (p=0.01), and no changes were
      observed in the reflex latency and subjective pain sensation (p>0.05). No
      significant changes were observed in the CSP duration in subjects who received
      the placebo (all, p>0.05). Our results indicate that escitalopram increases the
      central disposition of serotonin and increases the activity of the spinal
      inhibitory interneurons on the alpha-motoneurons of the hand muscles. Thus, our
      results indicate the involvement of the monoaminergic system in controlling the
      spinal pain mechanisms by supraspinal descending pathways originating from the
      brainstem neural structures. 

PMID- 24589882
TI  - [Preclinical emergency medicine].

PMID- 24589883
TI  - [The golden hour of sepsis: initial therapy should start in the prehospital
      setting].
AB  - BACKGROUND: Sepsis is a common, time-urgent emergency that is still associated
      with a high mortality and morbidity rate. A strong correlation between the onset
      of therapy and survival has been shown. With every hour of delay, survival
      decreases by 7.6 %. In 2001, four treatment goals that should be performed in the
      first 6 h of treatment were developed. These form the basis of early goal
      directed therapy (EDGT) which is accepted as the standard of treatment for sepsis
      in the emergency department. OBJECTIVES: More than half of patients are admitted
      to the hospital by medical emergency services. Up to 40 % receive prehospital
      therapy with i.v. fluids and stabilization of vital signs according to the goals
      of EDGT. The diagnosis of sepsis is difficult if characteristic symptoms or
      parameters such as in the ST segment elevation myocardial infarction are lacking.
      However, 90 % of patients present with fever. CONCLUSIONS: Body temperature
      should always be assessed by paramedics. In addition, sepsis must always be
      considered as part of the differential diagnosis. If the suspicion cannot be
      ruled out, immediate therapy has to be initiated. Concerning the prehospital use
      of antibiotics, preliminary results of a study from the center of sepsis control
      and care in Jena, Germany, showed that this therapy form seems to be safe and
      effective, but further evaluation is necessary.

PMID- 24589884
TI  - Using ancillary ligands to tune the DNA binding properties of self-assembled
      luminescent metallomacrocycles.
AB  - The optical response, binding parameters, and duplex DNA binding mode of water
      soluble kinetically inert tetranuclear metallomacrocycles can all be controlled
      by judicious selection of ancillary ligands. 

PMID- 24589885
TI  - Targeted delivery of pharmacological chaperones for Gaucher disease to
      macrophages by a mannosylated cyclodextrin carrier.
AB  - Gaucher disease (GD) is a rare monogenetic disorder leading to dysfunction of
      acid beta-glucosidase (beta-glucocerebrosidase; GCase) and accumulation of
      glucosylceramide in lysosomes, especially in macrophages (Gaucher cells). Many of
      the mutations at the origin of GD do not impair the catalytic activity of GCase,
      but cause misfolding and subsequent degradation by the quality control system at
      the endoplasmic reticulum. Pharmacological chaperones (PCs) capable of restoring
      the correct folding and trafficking of the endogenous mutant enzyme represent
      promising alternatives to the currently available enzyme replacement and
      substrate reduction therapies (ERT and SRT, respectively), but unfavorable
      biodistribution and potential side-effects remain important issues. We have now
      designed a strategy to enhance the controlled delivery of PCs to macrophages that
      exploit the formation of ternary complexes between the PC, a trivalent
      mannosylated beta-cyclodextrin (betaCD) conjugate and the macrophage mannose
      receptor (MMR). First, PC candidates with appropriate relative avidities towards
      the betaCD cavity and the GCase active site were selected to ensure efficient
      transfer of the PC cargo from the host to the GCase active site. Control
      experiments confirmed that the betaCD carrier was selectively recognized by
      mannose-specific lectins and that the corresponding PC:mannosylated betaCD
      supramolecular complex retained both the chaperoning activity, as confirmed in
      human GD fibroblasts, and the MMR binding ability. Finally, fluorescence
      microscopy techniques proved targeting and cellular uptake of the PC-loaded
      system in macrophages. Altogether, the results support that combined cyclodextrin
      encapsulation and glycotargeting may improve the efficacy of PCs for GD. 

PMID- 24589886
TI  - Hemimegalencephaly without epilepsy: case report.
AB  - Hemimegalencephaly is a rare sporadic brain malformation characterized by
      enlargement of one cerebral hemisphere. The classical clinical triad consists of
      intractable epilepsy, severe psychomotor delay and hemiparesis. In this report,
      we describe a case of a 3-year-old girl, with all the radiological features of
      severe hemimegalencephaly but with a comparatively benign clinical course. She
      had no hemiparesis, mild delay and no seizures. An extensive literature review
      reveals only one previously reported case of hemimegalencephaly with the absence
      of seizures, as part of case series. This is the first dedicated case report,
      with clinical description and radiological images, of this entity. 

PMID- 24589887
TI  - CB1 cannabinoid receptor stimulation during adolescence impairs the maturation of
      GABA function in the adult rat prefrontal cortex.
AB  - Converging epidemiological studies indicate that cannabis abuse during
      adolescence increases the risk of developing psychosis and prefrontal cortex
      (PFC)-dependent cognitive impairments later in life. However, the mechanisms
      underlying the adolescent susceptibility to chronic cannabis exposure are poorly
      understood. Given that the psychoactive constituent of cannabis binds to the CB1
      cannabinoid receptor, the present study was designed to determine the impact of a
      CB1 receptor agonist (WIN) during specific windows of adolescence on the
      functional maturation of the rat PFC. By means of local field potential
      recordings and ventral hippocampal stimulation in vivo, we found that a history
      of WIN exposure during early (postnatal days - P35-40) or mid-(P40-45)
      adolescence, but not in late adolescence (P50-55) or adulthood (P75-80), is
      sufficient to yield a state of frequency-dependent prefrontal disinhibition in
      adulthood comparable to that seen in the juvenile PFC. Remarkably, this
      prefrontal disinhibition could be normalized following a single acute local
      infusion of the GABA-Aalpha1 positive allosteric modulator Indiplon, suggesting
      that adolescent exposure to WIN causes a functional downregulation of GABAergic
      transmission in the PFC. Accordingly, in vitro recordings from adult rats exposed
      to WIN during adolescence demonstrate that local prefrontal GABAergic
      transmission onto layer V pyramidal neurons is markedly reduced to the level seen
      in the P30-35 PFC. Together, these results indicate that early and mid
      adolescence constitute a critical period during which repeated CB1 receptor
      stimulation is sufficient to elicit an enduring state of PFC network
      disinhibition resulting from a developmental impairment of local prefrontal
      GABAergic transmission.

PMID- 24589888
TI  - Preferential loss of dorsal-hippocampus synapses underlies memory impairments
      provoked by short, multimodal stress.
AB  - The cognitive effects of stress are profound, yet it is unknown if the
      consequences of concurrent multiple stresses on learning and memory differ from
      those of a single stress of equal intensity and duration. We compared the effects
      on hippocampus-dependent memory of concurrent, hours-long light, loud noise,
      jostling and restraint (multimodal stress) with those of restraint or of loud
      noise alone. We then examined if differences in memory impairment following these
      two stress types might derive from their differential impact on hippocampal
      synapses, distinguishing dorsal and ventral hippocampus. Mice exposed to hours
      long restraint or loud noise were modestly or minimally impaired in novel object
      recognition, whereas similar-duration multimodal stress provoked severe deficits.
      Differences in memory were not explained by differences in plasma corticosterone
      levels or numbers of Fos-labeled neurons in stress-sensitive hypothalamic
      neurons. However, although synapses in hippocampal CA3 were impacted by both
      restraint and multimodal stress, multimodal stress alone reduced synapse numbers
      severely in dorsal CA1, a region crucial for hippocampus-dependent memory.
      Ventral CA1 synapses were not significantly affected by either stress modality.
      Probing the basis of the preferential loss of dorsal synapses after multimodal
      stress, we found differential patterns of neuronal activation by the two stress
      types. Cross-correlation matrices, reflecting functional connectivity among
      activated regions, demonstrated that multimodal stress reduced hippocampal
      correlations with septum and thalamus and increased correlations with amygdala
      and BST. Thus, despite similar effects on plasma corticosterone and on
      hypothalamic stress-sensitive cells, multimodal and restraint stress differ in
      their activation of brain networks and in their impact on hippocampal synapses.
      Both of these processes might contribute to amplified memory impairments
      following short, multimodal stress. 

PMID- 24589890
TI  - Epigenetics and the war on mental illness.

PMID- 24589891
TI  - Dopamine transporter imaging: nonindependence of regional measures.

PMID- 24589889
TI  - Dopamine and serotonin signaling during two sensitive developmental periods
      differentially impact adult aggressive and affective behaviors in mice.
AB  - Pharmacologic blockade of monoamine oxidase A (MAOA) or serotonin transporter (5
      HTT) has antidepressant and anxiolytic efficacy in adulthood. Yet, genetically
      conferred MAOA or 5-HTT hypoactivity is associated with altered aggression and
      increased anxiety/depression. Here we test the hypothesis that increased
      monoamine signaling during development causes these paradoxical aggressive and
      affective phenotypes. We find that pharmacologic MAOA blockade during early
      postnatal development (P2-P21) but not during peri-adolescence (P22-41) increases
      anxiety- and depression-like behavior in adult (>P90) mice, mimicking the effect
      of P2-21 5-HTT inhibition. Moreover, MAOA blockade during peri-adolescence, but
      not P2-21 or P182-201, increases adult aggressive behavior, and 5-HTT blockade
      from P22-P41 reduced adult aggression. Blockade of the dopamine transporter, but
      not the norepinephrine transporter, during P22-41 also increases adult aggressive
      behavior. Thus, P2-21 is a sensitive period during which 5-HT modulates adult
      anxiety/depression-like behavior, and P22-41 is a sensitive period during which
      DA and 5-HT bi-directionally modulate adult aggression. Permanently altered
      DAergic function as a consequence of increased P22-P41 monoamine signaling might
      underlie altered aggression. In support of this hypothesis, we find altered
      aggression correlating positively with locomotor response to amphetamine
      challenge in adulthood. Proving that altered DA function and aggression are
      causally linked, we demonstrate that optogenetic activation of VTA DAergic
      neurons increases aggression. It therefore appears that genetic and pharmacologic
      factors impacting dopamine and serotonin signaling during sensitive developmental
      periods can modulate adult monoaminergic function and thereby alter risk for
      aggressive and emotional dysfunction. 

PMID- 24589892
TI  - GPNMB/OA protein increases the invasiveness of human metastatic prostate cancer
      cell lines DU145 and PC3 through MMP-2 and MMP-9 activity.
AB  - Non-metastatic glycoprotein melanoma protein B (GPNMB), also known as
      osteoactivin (OA) is expressed in a wide array of tumors and represents an
      emerging target for drug development. In this study, we investigated the role of
      GPNMB/OA in the progression of human metastatic DU145 and PC3 prostate cancer
      cells. GPNMB/OA contribution in PCa malignant phenotype has been analyzed by
      small interfering RNA-induced GPNMB/OA silencing. We found that following
      GPNMB/OA silencing the migration capability of both DU145 and PC3 cells,
      evaluated by using in vitro invasivity assay, as well as the metalloproteinases
      MMP-2 and MMP-9 activity were equally strongly inhibited. By contrast knocking
      down GPNMB/OA weakly attenuated cell proliferation rate of DU145, an effect that
      paralleled with an increase number of apoptotic cells. However, PC3 cell growth
      seems to be not affected by GPNMB/OA. Together, these data reveal that GPNMB/OA
      acts as a critical molecular mediator promoting the acquisition of the more
      aggressive, pro-metastatic phenotype distinctive of human DU145 and PC3 cell
      lines. 

PMID- 24589894
TI  - Hepatocellular carcinoma: reasons for phase III failure and novel perspectives on
      trial design.
AB  - Hepatocellular carcinoma (HCC) is a major health problem. Most patients with HCC
      experience a recurrence after resection/ablation or are diagnosed at advanced
      stages. Sorafenib remains the only approved systemic drug for these patients.
      Molecular therapies targeting signaling cascades involved in hepatocarcinogenesis
      have been explored in phase III clinical trials. However, none of the drugs
      tested have shown positive results in the first-line (brivanib, sunitinib,
      erlotinib, and linifanib) or second-line (brivanib, everolimus) setting after
      sorafenib progression. Reasons for failure are heterogeneous and include lack of
      understanding of critical drivers of tumor progression/dissemination, liver
      toxicity, flaws in trial design, or marginal antitumoral potency. These trials
      are also challenging time to progression as a surrogate endpoint of survival.
      Trials ongoing testing drugs head-to-head versus sorafenib in "all comers" might
      have difficulties in achieving superior results in the first line. Novel trials
      are also designed testing drugs in biomarker-based subpopulations of patients
      with HCC. Most common mutations, however, are undruggable, such as p53 and
      CTNNB1. Two types of studies are proposed: (i) phase II pivotal proof-of-concept
      studies testing drugs blocking potential oncogenic addiction loops, such as the
      one testing MEK inhibitors in RAS(+) patients or amplification of FGF19 as a
      target; and (ii) phase II to III studies using biomarker-based trial enrichment
      for defining HCC subpopulations, such as the case of enriching for MET-positive
      tumors. These strategies have been deemed successful in breast, melanoma, and
      lung cancers, and are expected to change the landscape of trial design of HCC.

PMID- 24589893
TI  - Phospholipids: molecules regulating cytoskeletal organization in plant abiotic
      stress tolerance.
AB  - Cytoskeleton serves as structural, membrane-bound and highly nonlinear dynamics
      element that basically functions in abiotic and biotic stresses. The study of
      phospholipid-regulated cytoskeletal organization to strengthen plants against
      stresses is emerging. Phospholipids in lipid bilayers, as the main compound of
      cellular membranes, have roles in modulation of membrane curvature and anchoring,
      cross-linking or regulating particular cytoskeletal proteins to modulate
      cytoskeletal dynamics. In this review, we highlight the role of phospholipids and
      their metabolic enzymes through regulating cytoskeletal organization and dynamics
      in response to abiotic stresses, such as salt, drought and low/high temperature
      stresses. 

PMID- 24589895
TI  - Spreading the word-your word, that is: writing clinical articles for publication.

PMID- 24589896
TI  - Radiographic confirmation of feeding tube placement: a diagnostic tool
      identifying gastrointestinal anomalies.

PMID- 24589897
TI  - NICU parent-to-parent partnerships: a comprehensive approach.
AB  - Parents of newborns in the neonatal intensive care unit (NICU) find themselves in
      a world of unknown medical terminology, advanced technology, and the realization
      that their dream of a healthy baby has been shattered. The unique partnership
      with trained parent-to-parent volunteers, who have had previous NICU experiences,
      enhances professional support and helps new NICU parents adjust to these
      unexpected challenges. This practice-based article describes the Helen DeVos
      Children's Hospital NICU Parent-to-Parent Partnership's (PPP) 40-year commitment
      to the parent-to-parent philosophy and its comprehensive approach to delivering
      trained volunteer PPP services to NICU families. A historical review of the
      literature, including this hospital's original research, current programming,
      recruiting, training, supervision, and survey feedback, is outlined. 

PMID- 24589898
TI  - Impact of a parent-directed pamphlet about pain management during infant
      vaccinations on maternal knowledge and behavior.
AB  - PURPOSE: To evaluate the impact of a parent-directed instructional pamphlet about
      managing pain during infant vaccinations. DESIGN AND SAMPLE: New mothers
      hospitalized following birth of an infant at two hospitals participated in a
      "before-and-after" study. In the "after" phase, the pamphlet was passively
      inserted in discharge packages at the intervention hospital. MAIN OUTCOMES:
      Maternal knowledge and self-reported use of pain-management interventions during
      routine infant two-month vaccinations. RESULTS: Altogether, 354 mothers
      participated. A two-way (site, phase) ANOVA revealed no interaction (site 3
      phase) in knowledge or use of pain-management strategies after routine two-month
      infant vaccinations; hence, there was no evidence of a benefit provided by the
      pamphlet. However, within the intervention site, only 21 percent of mothers read
      the pamphlet. Reading the pamphlet was associated with higher knowledge. This
      suggests some possible benefits of the pamphlet, provided that mothers read it.

PMID- 24589899
TI  - Fluconazole administration leading to anaphylactic shock in a preterm newborn.
AB  - Preterm infants, born with immature innate immunity, are less likely to develop
      anaphylaxis. Fluconazole prophylaxis during the first six weeks of life decreases
      invasive candidiasis in very low birth weight infants. Adverse effects of
      fluconazole are very rare. In this study, we report a newborn (a male, 26 weeks
      gestation and 900 g birth weight) who developed anaphylaxis after fluconazole
      administration. Hypotension and erythematous rash were present. We believe this
      to be the first anaphylaxis case in newborns caused by fluconazole in literature.
      Clinicians should be aware of the possibility of this potentially fatal adverse
      effect occurring with intravenous fluconazole. 

PMID- 24589900
TI  - Parental quality of life: caring for an infant or toddler with a tracheostomy at
      home.
AB  - PURPOSE: To explore the relationships between stress, coping, duration of
      tracheostomy, and quality of life (QOL) of parental caregivers who care for a
      child with a tracheostomy at home. DESIGN: A cross-sectional correlational design
      was used to study parents who care for a child with a tracheostomy at home.
      Family Inventory of Life Events, Family Crisis Oriented Personal Evaluation
      Scale, and Psychological General Well-Being Index were used to measure stress,
      coping, and QOL, respectively. Data were collected using both online and paper
      pencil format. MAIN OUTCOME VARIABLE: quality of life. RESULTS: Parents who care
      for their infants/toddlers with a tracheostomy at home were found to be in
      moderate distress. Mean age of the participants was 33 years (N = 71), and the
      average duration of the child's tracheotomy was 18.22 (SD = 9.59) months.
      Multivariate analysis showed a significant inverse relationship between QOL and
      stress. QOL was significantly associated with coping, B = 19.91, beta = .43, p
      <.001.

PMID- 24589901
TI  - A review of drug therapy for neonatal hypertension.
AB  - Neonatal hypertension is becoming a more common diagnosis because of higher
      survival rates in premature infants and the need for intravascular access and
      invasive blood pressure (BP) monitoring. Defining hypertension in the neonatal
      population has been challenging, and understanding what constitutes a normal BP
      is still evolving.Five general classes of antihypertensives exist for the
      treatment of hypertension in neonates. Few studies are available to guide
      clinicians in the treatment of hypertension in neonates, and limited data exist
      regarding outcomes of hypertension in the neonatal period. 

PMID- 24589902
TI  - Nursing assessment of guaiac-positive and occult blood in preterm infant stools.
AB  - Guaiac testing the stool of very low birth weight (VLBW; <1,500 g) preterm
      infants has been a standard of care for many neonatal intensive care units
      (NICUs) and considered a diagnostic tool that could potentially provide early
      warning of gastrointestinal disturbances, feeding intolerance (FI), or
      necrotizing enterocolitis (NEC). Evidence to either support or eliminate testing
      stool for occult blood from standard care practices is lacking. Support to
      eliminate testing is often based on the knowledge that neonatal treatment
      interventions-such as gastric tube placement, intubation, and/or suctioning- may
      often result in occult blood in stools. However, there is also reasonable concern
      that occult blood may indicate a cascade of pathophysiological events, which may
      lead to FI and NEC, is in progress.Feeding intolerance remains one of the most
      consistent reasons VLBW preterm infants experience poor weight gain and extended
      hospital stays. Every nursing assessment is strategic to the early identification
      of contributing factors to either the development of FI or NEC. Including low
      cost, noninvasive diagnostic tools to augment the findings of the nursing
      assessment can only help guide health care providers in appropriate decision
      making related to the feeding plan. 

PMID- 24589903
TI  - What happens when the board of nursing comes calling: investigation and
      disciplinary actions.
AB  - Each state has a Board of Nursing that governs the nurses that practice in that
      state. Each Board of Nursing has a process by which it investigates and hears
      cases against nurses accused of wrongdoing. This article gives a general overview
      of what steps are usually taken when the Board of Nursing suspects that a nurse's
      actions may be in violation of the laws that govern nursing practice. 

PMID- 24589908
TI  - The c.480C>G polymorphism of hOCT1 influences imatinib clearance in patients
      affected by chronic myeloid leukemia.
AB  - The aim of the study was to investigate any possible influence of polymorphisms
      of transmembrane transporters human organic cation transporter 1 (hOCT1), ABCB1,
      ABCG2 on imatinib pharmacokinetics in 33 men and 27 women (median age and range,
      56 and 27-79 years, respectively) affected by chronic myeloid leukemia. A
      population pharmacokinetic analysis was performed to investigate imatinib
      disposition in every patient and the role of transporter polymorphisms. Results
      showed that the alpha1-acid glycoprotein and the c.480C>G genotype of hOCT1 had a
      significant effect on apparent drug clearance (CL/F) being responsible,
      respectively, for a 20% and 10% decrease in interindividual variability (IIV) of
      CL/F (from 50.1 up to 19.6%). Interestingly, 25 patients carrying at least one
      polymorphic c.480 G allele had a significant lower CL/F value with respect to the
      35 c.480CC individuals (mean+/-s.d., 9.6+/-1.6 vs 12.1+/-2.3 l h(-1),
      respectively; P<0.001). In conclusion, the hOCT1 c.480C>G SNP may significantly
      influence imatinib pharmacokinetics, supporting further analyses in larger groups
      of patients. 

PMID- 24589909
TI  - Effect of risperidone metabolism and P-glycoprotein gene polymorphism on QT
      interval in patients with schizophrenia.
AB  - Risperidone (RIS) is a frequently used efficacious psychotropic drug. However, it
      prolongs the QTc interval and may cause fatal arrhythmia. Little is known on the
      determinants of this RIS side effect. RIS is metabolized by CYP2D6, and is
      subject to drug efflux by P-glycoprotein (P-gp) encoded by the ATP-binding
      cassette subfamily B member 1 (ABCB1) gene. P-gp removes both RIS and its
      metabolite 9-OH-RIS from cardiac tissue. To investigate the effect of RIS
      metabolism and ABCB1 gene polymorphisms on QTc, steady-state plasma RIS and 9-OH
      RIS levels, and QTc were measured. CYP2D6, ABCB1 C3435T and G2677T/A genotypes
      were determined in 66 schizophrenia patients on RIS. QTc was significantly longer
      in patients with ABCB1 3435CT+3435 TT than in those with 3435CC (P=0.006). ABCB1
      G2677T/A genotype did not affect QTc. Multiple regression analysis showed that
      C/T or T/T genotypes at the ABCB1 C3435T locus, lower weight, and older age
      prolonged QTc. In summary, the T allele of the ABCB1 C3435T genotype should be
      considered in future diagnostic development efforts for RIS-associated QT. 

PMID- 24589911
TI  - Trends in anemia care in older patients approaching end-stage renal disease in
      the United States (1995-2010).
AB  - IMPORTANCE: Anemia is common in patients with advanced chronic kidney disease.
      Whereas the treatment of anemia in patients with end-stage renal disease (ESRD)
      has attracted considerable attention, relatively little is known about patterns
      and trends in the anemia care received by patients before they start maintenance
      dialysis or undergo preemptive kidney transplantation. OBJECTIVE: To determine
      the trends in anemia treatment received by Medicare beneficiaries approaching
      ESRD. DESIGN, SETTING, AND PARTICIPANTS: Closed cohort study in the United States
      using national ESRD registry data (US Renal Data System) of patients 67 years or
      older who initiated maintenance dialysis or underwent preemptive kidney
      transplantation between 1995 and 2010. All eligible patients had uninterrupted
      Medicare (A+B) coverage for at least 2 years before ESRD. EXPOSURE: Time, defined
      as calendar year of incident ESRD. MAIN OUTCOMES AND MEASURES: Use of
      erythropoiesis-stimulating agents (ESA), intravenous iron supplements, and blood
      transfusions in the 2 years prior to ESRD; hemoglobin concentration at the time
      of ESRD. We used multivariable modified Poisson regression to estimate
      utilization prevalence ratios (PRs). RESULTS: Records of 466,803 patients were
      analyzed. The proportion of patients with incident ESRD receiving any ESA in the
      2 years before increased from 3.2% in 1995 to a peak of 40.8% in 2007;
      thereafter, ESA use decreased modestly to 35.0% in 2010 (compared with 1995; PR,
      9.85 [95% CI, 9.04-10.74]). Among patients who received an ESA, median time from
      first recorded ESA use to ESRD increased from 120 days in 1995 to 337 days in
      2010. Intravenous iron administration increased from 1.2% (1995) to 12.3% (2010;
      PR, 9.20 [95% CI, 7.97-10.61]). The proportion of patients receiving any blood
      transfusions increased monotonically from 20.6% (1995) to 40.3% (2010; PR, 1.88
      [95% CI, 1.82-1.95]). Mean hemoglobin concentrations were 9.5 g/dL in 1995,
      increased to a peak of 10.3 g/dL in 2006, and then decreased moderately to 9.9
      g/dL in 2010. CONCLUSIONS AND RELEVANCE: Between 1995 and 2010, older adults
      approaching ESRD were increasingly more likely to be treated with ESAs and to
      receive intravenous iron supplementation, but also more likely to receive blood
      transfusions.

PMID- 24589912
TI  - A novel silk-TCP-PEEK construct for anterior cruciate ligament reconstruction: an
      off-the shelf alternative to a bone-tendon-bone autograft.
AB  - Bone-tendon-bone autograft represents a gold-standard for anterior cruciate
      ligament (ACL) reconstruction but at the cost of a secondary surgical site that
      can be accompanied by functional impairment and discomfort. Although numerous in
      vitro and in vivo studies have investigated tissue engineering alternatives to
      autografting, the achievement of a functional histological transition between
      soft and hard tissue has remained elusive. To bridge this gap we developed and
      tested a novel multiphase scaffold of silk, tricalcium phosphate (TCP) and
      polyether ether ketone for ACL reconstruction. We present in vitro biomechanical
      tests demonstrating that the construct recapitulates native ACL function under
      typical physiological loads. A pilot in vivo experiment in two pigs with a three
      month follow-up showed a robust histological transition between regenerated
      fibrous tissue and the margins of the bone tunnel, with histological features
      similar to the native ACL to bone insertion. These histological observations
      suggest that the construct was stably anchored until TCP incorporation to the
      host tissues. On the strength of these preliminary results, we conclude that the
      described approach may offer a promising alternative to autograft for ACL
      reconstruction. This study thus provides proof for a concept that warrants
      further development. 

PMID- 24589910
TI  - Gene expression analysis in RA: towards personalized medicine.
AB  - Gene expression has recently been at the forefront of advance in personalized
      medicine, notably in the field of cancer and transplantation, providing a
      rational for a similar approach in rheumatoid arthritis (RA). RA is a prototypic
      inflammatory autoimmune disease with a poorly understood etiopathogenesis.
      Inflammation is the main feature of RA; however, many biological processes are
      involved at different stages of the disease. Gene expression signatures offer
      management tools to meet the current needs for personalization of RA patients'
      care. This review analyses currently available information with respect to RA
      diagnostic, prognostic and prediction of response to therapy with a view to
      highlight the abundance of data, whose comparison is often inconclusive due to
      the mixed use of material source, experimental methodologies and analysis tools,
      reinforcing the need for harmonization if gene expression signatures are to
      become a useful clinical tool in personalized medicine for RA patients.

PMID- 24589913
TI  - Comparison of the effects of the repetition rate between microsecond and
      nanosecond pulses: electropermeabilization-induced electro-desensitization?
AB  - BACKGROUND: Applications of cell electropermeabilization are rapidly growing but
      basic concepts are still unclear. In particular, the impact of electric pulse
      repetition rate in the efficiency of permeabilization has not yet been
      understood. METHODS: The impact of electric pulse repetition rate in the
      efficiency of permeabilization was analyzed in experiments performed on potato
      tissue and partially transposed on mice liver. On potato tissue, pulses with
      durations of 100MUs or 10ns are applied. The intensity of permeabilization was
      quantified by means of bioimpedance changes and electric current measurements and
      a new index was defined. RESULTS: For the two pulse durations tested, very low
      repetition rates (below 0.1Hz) are much more efficient to achieve cell
      permeabilization in potato tissue. In mice liver, using 100MUs pulses, the
      influence of the repetition rate is more complex. Indeed, repetition rates of 1Hz
      and 10Hz are more efficient than 100Hz or 1kHz, but not the repetition rate of
      0.1Hz for which there is an impact of the living mice organism response.
      CONCLUSIONS: We propose that the effects reported here might be caused by an
      electroporation-induced cell membrane 'electro-desensitization' which requires
      seconds to dissipate due to membrane resealing. GENERAL SIGNIFICANCE: This study
      not only reinforces previous observations, but moreover it sustains a new concept
      of 'electro-desensitization' which is the first unifying mechanism enabling to
      explain all the results obtained until now both in vitro and in vivo, with long
      and short pulses.

PMID- 24589914
TI  - Comparison of random forest and parametric imputation models for imputing missing
      data using MICE: a CALIBER study.
AB  - Multivariate imputation by chained equations (MICE) is commonly used for imputing
      missing data in epidemiologic research. The "true" imputation model may contain
      nonlinearities which are not included in default imputation models. Random forest
      imputation is a machine learning technique which can accommodate nonlinearities
      and interactions and does not require a particular regression model to be
      specified. We compared parametric MICE with a random forest-based MICE algorithm
      in 2 simulation studies. The first study used 1,000 random samples of 2,000
      persons drawn from the 10,128 stable angina patients in the CALIBER database
      (Cardiovascular Disease Research using Linked Bespoke Studies and Electronic
      Records; 2001-2010) with complete data on all covariates. Variables were
      artificially made "missing at random," and the bias and efficiency of parameter
      estimates obtained using different imputation methods were compared. Both MICE
      methods produced unbiased estimates of (log) hazard ratios, but random forest was
      more efficient and produced narrower confidence intervals. The second study used
      simulated data in which the partially observed variable depended on the fully
      observed variables in a nonlinear way. Parameter estimates were less biased using
      random forest MICE, and confidence interval coverage was better. This suggests
      that random forest imputation may be useful for imputing complex epidemiologic
      data sets in which some patients have missing data. 

PMID- 24589915
TI  - The carbomethylation of arylacrylamides leading to 3-ethyl-3-substituted indolin
      2-one by cascade radical addition/cyclization.
AB  - An FeCl2-promoted carbomethylation of arylacrylamides by di-tert-butyl peroxide
      (DTBP) is achieved, leading to 3-ethyl-3-substituted indolin-2-one in high yield.
      The reaction tolerates a series of functional groups, such as cyano, nitro,
      ethyloxy carbonyl, bromo, chloro, and trifluoromethyl groups. The radical
      methylation and arylation of the alkenyl group are involved in this reaction. 

PMID- 24589916
TI  - Impact of initial tumor volume on radiotherapy outcome in patients with T2
      glottic cancer.
AB  - BACKGROUND: The aim of this study was to quantify the impact of initial tumor
      volume (TV) on radiotherapy (RT) outcome in patients with T2 glottic cancer.
      MATERIALS AND METHODS: Initial TV was calculated for 115 consecutive patients
      with T2 glottic cancer who had been treated with definitive RT alone at a single
      institution. RESULTS: The results showed strong correlations of TV with 3-year
      local tumor control (LTC) and disease-free survival (DFS). For TV <= 0.7 cm(3), 3
      year LTC was 83%; for TV 0.7-3.6 cm(3) this was 70% and for TV 3.6-17 cm(3) 44%.
      Analysis of total dose vs. initial TV showed that larger T2 glottic tumors with a
      TV of around 5 cm(3) (2-2.5 cm in diameter with 10(10) cancer cells) need an
      extra 6.5 Gy to achieve similar 3-year LTC rates as for small tumors with a TV of
      0.5 cm(3) (~1 cm in diameter with 10(9) cancer cells). CONCLUSION: Although
      classification of tumors according to TV cannot replace TNM staging in daily
      practice, it could represent a valuable numerical supplement for planning the
      optimal dose fractionation scheme for individual patients.

PMID- 24589917
TI  - Effectiveness and safety of proton beam therapy for advanced hepatocellular
      carcinoma with portal vein tumor thrombosis.
AB  - PURPOSE: To evaluate the clinical effectiveness and safety of proton beam therapy
      (PBT) in advanced hepatocellular carcinoma (HCC) patients with portal vein tumor
      thrombosis (PVTT). PATIENTS AND METHODS: Twenty-seven HCC patients with PVTT
      underwent PBT, including 22 patients with modified International Union Against
      Cancer (mUICC) stage IVA,five patients with stage IVB primary tumors, and 16 with
      main PVTT. A median dose of 55 GyE (range, 50-66 GyE) in 20-22 fractions was
      delivered to a target volume encompassing both the PVTT and primary tumor.
      RESULTS: Overall, treatment was well tolerated, with no toxicity of grade >= 3.
      Median overall survival (OS) times in all patients and in stage IVA patients were
      13.2 months and 16 months, respectively. Assessments of PVTT response showed
      complete response in 0 of 27 (0%) patients, partial response in 15 (55.6%),
      stable disease in 10 (37%), and progressive disease in 2 (7.4%) patients, with an
      objective response rate of 55.6%. PVTT responders showed significantly higher
      actuarial 1-year local progression-free survival (LPFS; 85.6% vs. 51.3%), relapse
      free survival (RFS; 20% vs. 0%) and OS (80% vs. 25%) rates than nonresponders
      (p<0.05 each). Multivariate analysis showed that PVTT response and mUICC stage
      were independent prognostic factors for OS. CONCLUSION: Our data suggest that PBT
      could improve LPFS, RFS, and OS in advanced HCC patients with PVTT and it is
      feasible and safe for these patients.

PMID- 24589918
TI  - Robotic radiosurgery as an alternative to brachytherapy for cervical cancer
      patients.
AB  - BACKGROUND AND PURPOSE: To compare MRI-guided brachytherapy (BT) and two
      different dose prescriptions for robotic radiosurgery (RRS) in locally advanced
      cervical cancer. METHODS AND MATERIALS: Eleven patients with FIGO stage IIB-IIIB
      cervical cancer underwent RRS instead of BT for various reasons. A total dose of
      30 Gy was administered in five fractions. The maximum dose was chosen such that
      the prescribed dose was 70 % of the maximum dose (RRS70). To simulate BT more
      closely, additional plan calculations were carried out for a higher maximum dose
      with the same enclosing dose of 30 Gy being now 25 % of the maximum dose (RRS25).
      BT plans were calculated for the same patients (BTRRS). Finally, the resulting
      three sets of treatment plans were compared with 38 other patients treated with
      MRI-guided BT and the same dose prescription (BTref). Plan comparisons were
      performed based on DVH parameters with regard to target coverage (V100),
      conformation number (CN), and sparing of the organs at risk (OARs). RESULTS: The
      best coverage of V100 = 100 +/- 0 % was obtained with RRS25, followed by RRS70
      with 97.1 +/- 2.7 %, BTref with 90.9 +/- 8.9 %, and the intraindividual BTRRS
      with 80.6 +/- 6.4 %. The sparing of OARs was associated with D0.1 cc, D2 cc, and
      D5 cc to the rectum, sigmoid, and bladder walls. OAR doses were compliant with
      the GEC-ESTRO guidelines and comparable among RRS70, RRS25, BTRRS, and BTref. By
      contrast, RRS25 could not fulfill these guidelines, exceeding considerably the
      tolerable dose constraints for the walls of the critical OARs. CONCLUSION:
      Despite of the excellent coverage and higher maximum dose, the unacceptably high
      exposure to the OARs disqualified RRS25 as an alternative for BT in cervical
      cancer patients. By contrast, RRS70 offered the best protection for the OARs,
      comparable to BT, and even better target coverage and conformity than BT.

PMID- 24589919
TI  - Biologically effective dose and definitive radiation treatment for localized
      prostate cancer: treatment gaps do affect the risk of biochemical failure.
AB  - BACKGROUND AND PURPOSE: It is not clear if prolongation of definitive external
      radiation therapy for prostate cancer has an effect on biochemical failure. The
      aim of this work was to evaluate whether the biologically effective dose (BED),
      and in particular the duration of radiotherapy, intended as overall treatment
      time, has an effect on biochemical failure rates and to develop a nomogram useful
      to predict the 6-year probability of biochemical failure. PATIENTS AND METHODS: A
      total of 670 patients with T1-3 N0 prostate cancer were treated with external
      beam definitive radiotherapy, to a total dose of 72-79.2 Gy in 40-44 fractions.
      The computed BED values were treated with restricted cubic splines. Variables
      were checked for colinearity using Spearman's test. The Kaplan-Meier method was
      used to calculate freedom from biochemical relapse (FFBR) rates. The Cox
      regression analysis was used to identify prognostic factors of biochemical
      relapse in the final most performing model and to create a nomogram. Concordance
      probability estimate and calibration methods were used to validate the nomogram.
      RESULTS: Neoadjuvant and concomitant androgen deprivation was administered to 475
      patients (70%). The median follow-up was 80 months (range 20-129 months).
      Overall, the 6-year FFBR rate was 88.3%. BED values were associated with higher
      biochemical failure risk. Age, iPSA, risk category, and days of radiotherapy
      treatment were independent variables of biochemical failure. CONCLUSION: A
      prolongation of RT (lower BED values) is associated with an increased risk of
      biochemical failure. The nomogram may be helpful in decision making for the
      individual patient.

PMID- 24589920
TI  - Image-guided stereotactic radiotherapy for patients with vestibular schwannoma. A
      clinical study.
AB  - INTRODUCTION: Local tumor control and functional outcome after linac-based
      stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (FSRT)
      for vestibular schwannoma (VS) were assessed. METHODS: In all, 250 patients with
      VS were treated: 190 patients with tumors < 2 cm diameter underwent SRS and 60
      patients with tumors >2 to 3.5 cm underwent FSRT. Dose prescription for all cases
      with SRS (n = 190, 76 %) was 13.5 Gy. For FSRT, mainly two hypofractionated
      schedules (n = 60, 24 %) with either 7 fractions of 5 Gy (total dose: 35 Gy; n =
      35) or 11 fractions of 3.8 Gy (total dose: 41.8 Gy; n = 16) were used. The
      primary endpoint was local tumor control. Secondary endpoints were symptomatic
      control and morbidity. RESULTS: The median follow-up was 33.8 months. The 3-year
      local tumor control was 88.9 %. Local control for SRS and FSRT was 88 and 92 %,
      respectively. For FSRT with 35 and 41.8 Gy, local control was 90 and 100 %,
      respectively. There were no acute reactions exceeding grade I. In 61 cases (24.4
      % of the entire cohort), trigeminal neuralgia was reported prior to treatment. At
      last follow-up, 16.3 % (10/61) of those patients reported relief of pain.
      Regarding facial nerve dysfunction, 45 patients (18 %) presented with symptoms
      prior to RT. At the last follow-up, 13.3% (6/45) of those patients reported a
      relief of dysesthesia. CONCLUSION: Using SRS to treat small VS results in good
      local control rates. FSRT for larger lesions also seems effective. Severe
      treatment-related complications are not frequent. Therefore, image-guided
      stereotactic radiotherapy is an appropriate alternative to microsurgery for
      patients with VS.

PMID- 24589921
TI  - Squamous cell carcinoma of the larynx with subglottic extension: is larynx
      preservation possible?
AB  - PURPOSE: Squamous cell carcinoma of larynx with subglottic extension (sSCC) is a
      rare location described to carry a poor prognosis. The aim of this study was to
      analyze outcomes and feasibility of larynx preservation in sSCC patients.
      PATIENTS AND METHODS: Between 1996 and 2012, 197 patients with sSCC were treated
      at our institution and included in the analysis. Stage III-IV tumors accounted
      for 76%. Patients received surgery (62%), radiotherapy (RT) (18%), or induction
      chemotherapy (CT) (20%) as front-line therapy. RESULTS: The 5-year actuarial
      overall survival (OS), locoregional control (LRC), and distant control rate were
      59% (95% CI 51-68), 83% (95% CI 77-89), and 88% (95% CI 83-93), respectively,
      with a median follow-up of 54.4 months. There was no difference in OS and LRC
      according to front-line treatments or between primary subglottic cancer and
      glottosupraglottic cancers with subglottic extension. In the multivariate
      analysis, age > 60 years and positive N stage were the only predictors for OS (HR
      2, 95% CI 1.2-3.6; HR1.9, 95% CI 1-3.5, respectively). A lower LRC was observed
      for T3 patients receiving a larynx preservation protocol as compared with those
      receiving a front-line surgery (HR 14.1, 95% CI 2.5-136.7; p = 0.02); however, no
      difference of ultimate LRC was observed according to the first therapy when
      including T3 patients who underwent salvage laryngectomy (p = 0.6). In patients
      receiving a larynx preservation protocol, the 5-year larynx-preservation rate was
      55% (95% CI 43-68), with 36% in T3 patients. The 5-year larynx preservation rate
      was 81% (95% CI 65-96) and 35% (95% CI 20-51) for patients who received RT or
      induction CT as a front-line treatment, respectively. CONCLUSION: Outcomes of
      sSCC are comparable with other laryngeal cancers when managed with modern
      therapeutic options. Larynx-preservation protocols could be a suitable option in
      T1-T2 (RT or chemo-RT) and selected T3 sSCC patients (induction CT).

PMID- 24589923
TI  - A regio- and stereoselective entry to (Z)-beta-halo alkenyl sulfides and their
      applications to access stereodefined trisubstituted alkenes.
AB  - A mild and efficient preparation of (Z)-beta-halo alkenyl sulfides via the K2CO3
      promoted hydrothiolation of haloalkynes has been realized, producing (Z)-beta
      bromo and (Z)-beta-chloro vinylic sulfides in high yields with excellent regio-
      and stereoselectivity. This approach covers a variety of substrates, including
      both aryl and alkyl haloalkynes. Meaningfully, it allows a facile access to
      stereodefined (Z)- or (E)-trisubstituted olefins featuring the iterative cross
      coupling of carbon-halide and carbon-sulfur bonds of beta-halo alkenyl sulfides. 

PMID- 24589924
TI  - Immune cell-poor melanomas benefit from PD-1 blockade after targeted type I IFN
      activation.
AB  - Infiltration of human melanomas with cytotoxic immune cells correlates with
      spontaneous type I IFN activation and a favorable prognosis. Therapeutic blockade
      of immune-inhibitory receptors in patients with preexisting lymphocytic
      infiltrates prolongs survival, but new complementary strategies are needed to
      activate cellular antitumor immunity in immune cell-poor melanomas. Here, we show
      that primary melanomas in Hgf-Cdk4(R24C) mice, which imitate human immune cell
      poor melanomas with a poor outcome, escape IFN-induced immune surveillance and
      editing. Peritumoral injections of immunostimulatory RNA initiated a cytotoxic
      inflammatory response in the tumor microenvironment and significantly impaired
      tumor growth. This critically required the coordinated induction of type I IFN
      responses by dendritic, myeloid, natural killer, and T cells. Importantly,
      antibody-mediated blockade of the IFN-induced immune-inhibitory interaction
      between PD-L1 and PD-1 receptors further prolonged the survival. These results
      highlight important interconnections between type I IFNs and immune-inhibitory
      receptors in melanoma pathogenesis, which serve as targets for combination
      immunotherapies. SIGNIFICANCE: Using a genetically engineered mouse melanoma
      model, we demonstrate that targeted activation of the type I IFN system with
      immunostimulatory RNA in combination with blockade of immune-inhibitory receptors
      is a rational strategy to expose immune cell-poor tumors to cellular immune
      surveillance.

PMID- 24589926
TI  - Health care huddles: managing complexity to achieve high reliability.
AB  - BACKGROUND: Health care huddles are increasingly employed in a range of formats
      but theoretical mechanisms underlying huddles remain relatively uncharted.
      PURPOSE: A complexity science view implies that essential managerial strategies
      for high-performing health care organizations include meaningful conversations,
      enhanced relationships, and a learning culture. These three dimensions informed
      our approach to studying huddles. We explore new theories for how and why huddles
      have been useful in health care organizations. METHODS: We used a study design
      incorporating literature review, direct observation, and semistructured
      interviews. A complexity science framework guided data collection in three health
      care settings; we also incorporated theories on high-reliability organizations to
      analyze our observations and interpret huddle participants' perspectives.
      FINDINGS: We identify theoretical paths that could link huddles to improvement in
      patient safety outcomes. Huddles create time and space for conversations, enhance
      relationships, and strengthen a culture of safety. Huddles can be of particular
      value to health care organizations seeking or sustaining high reliability.
      PRACTICE IMPLICATIONS: Achieving high reliability, the organizational capacity to
      deliver what is intended to be delivered every time is difficult in complex
      systems. Managers have potential to create conditions from which huddle outcomes
      that support high reliability are more likely to emerge. Huddles support efforts
      to improve patient safety when they afford opportunities for heedful interactions
      to take place among individuals caring for patients and embed mindfulness into
      the organization.

PMID- 24589925
TI  - Efficacy of intermittent combined RAF and MEK inhibition in a patient with
      concurrent BRAF- and NRAS-mutant malignancies.
AB  - Vemurafenib, a RAF inhibitor, extends survival in patients with BRAF(V600)-mutant
      melanoma but activates extracellular signal-regulated kinase (ERK) signaling in
      RAS-mutant cells. In a patient with a BRAF(V600K)-mutant melanoma responding to
      vemurafenib, we observed accelerated progression of a previously unrecognized
      NRAS-mutant leukemia. We hypothesized that combining vemurafenib with a MAP-ERK
      kinase (MEK) inhibitor would inhibit ERK activation in the melanoma and prevent
      ERK activation by vemurafenib in the leukemia, and thus suppress both
      malignancies. We demonstrate that intermittent administration of vemurafenib led
      to a near-complete remission of the melanoma, and the addition of the MEK
      inhibitor cobimetinib (GDC-0973) caused suppression of vemurafenib-induced
      leukemic proliferation and ERK activation. Antimelanoma and antileukemia
      responses have been maintained for nearly 20 months, as documented by serial
      measurements of tumor-derived DNA in plasma in addition to conventional
      radiographic and clinical assessments of response. These data support testing of
      intermittent ERK pathway inhibition in the therapy for both RAS-mutant leukemia
      and BRAF-mutant melanoma.

PMID- 24589927
TI  - The relationship between voice climate and patients' experience of timely care in
      primary care clinics.
AB  - BACKGROUND: Aspects of the patient care experience, despite being central to
      quality care, are often problematic. In particular, patients frequently report
      problems with timeliness of care. As yet, research offers little insight on
      setting characteristics that contribute to patients' experience of timely care.
      PURPOSE: The aims of this study were to assess the relationship between
      organizational climate and patients' reports of timely care in primary care
      clinics and to broadly examine the link between staff's work environment and
      patient care experiences. We test hypotheses about the relationship between voice
      climate--staff feeling safe to speak up about issues--and reported timeliness of
      care, consistency in reported voice climate across professions, and how climate
      differences for various professions relate to timely care. METHODOLOGY: We
      conducted a cross-sectional study of employees (n = 1,121) and patients (n =
      8,164) affiliated with 37 clinics participating in a statewide reporting
      initiative. Employees were surveyed about clinics' voice climate, and patients
      were surveyed about the timeliness of care. Hypotheses were tested using analysis
      of variance and generalized estimating equations. FINDINGS: Clinical and
      administrative staff (e.g., nurses and office assistants) reported clinics'
      climates to be significantly less supportive of voice than did clinical leaders
      (e.g., physicians). The greater the difference in reported support for voice
      between professional groups, the less patients reported experiencing timely care
      in three respects: obtaining an appointment, seeing the doctor within 15 minutes
      of appointment time, and receiving test results. In clinics where staff reported
      climates supportive of voice, patients indicated receiving more timely care.
      Clinical leaders' reports of voice climate had no relationship to reported
      timeliness of care. PRACTICAL IMPLICATIONS: Our findings suggest the importance
      of clinics developing a strong climate for voice, particularly for clinical and
      administrative staff, to support better service quality for patients.

PMID- 24589928
TI  - Pressure effects on the electronic structure and superconducting critical
      temperature of Li2B2.
AB  - We present the structural, electronic and superconducting properties of Li2B2
      under pressure within the framework of the density functional theory. The
      structural parameters, electronic band structure, phonon frequency of the E2g
      phonon mode and superconducting critical temperature Tc were calculated for
      pressures up to 20 GPa. We predicted that the superconducting critical
      temperature of Li2B2 is about 11 K and this decreases as pressure increases. We
      found that even though the lattice dynamics of the E2g phonon mode is similar to
      MgB2, the reduction of the sigma-band density of states at Fermi level and the
      raising of the E2g phonon frequency with pressure were determinant to decrease
      lambda and consequently Tc. 

PMID- 24589929
TI  - Self-rated health changes and oldest-old mortality.
AB  - OBJECTIVES: This study explores how 2 measures of self-rated health (SRH) change
      are related to mortality among oldest-old adults. In doing so, it also considers
      how associations between SRH and mortality may depend on prior SRH. METHOD: Data
      come from the Asset and Health Dynamics survey--the oldest-old portion of the
      Health and Retirement Study-and follow 6,233 individuals across 13 years. I use
      parametric hazard models to examine relationships between death and 2 measures of
      short-term SRH change--a computed measure comparing SRH at time t-1 and t, and a
      respondent-provided retrospectively reported change. RESULTS: Respondents who
      demonstrate or report any SRH change between survey waves died at a greater rate
      than those with consistent SRH. After controlling for morbidity, individual
      characteristics, and SRH, those who changed SRH categories between survey waves
      and those who retrospectively reported an improvement in health continue to have
      a greater risk of death, when compared with those with no change. DISCUSSION:
      These findings suggest that the well-established associations between SRH status
      and mortality may understate the risk of death for oldest-old individuals with
      recent subjective health improvements.

PMID- 24589930
TI  - alphaEnv-decorated phosphatidylserine liposomes trigger phagocytosis of HIV-virus
      like particles in macrophages.
AB  - Macrophages represent an important cellular target of HIV-1. Interestingly, they
      are also believed to play a potential role counteracting its infection. However,
      HIV-1 is known to impair macrophage immune functions such as antibody-mediated
      phagocytosis. Here, we present immunoliposomes that can bind HIV-1 virus-like
      particles (HIV-VLPs) while being specifically phagocytosed by macrophages, thus
      allowing the co-internalization of HIV-VLPs. These liposomes are decorated with
      anti-Env antibodies and contain phosphatidylserine (PS). PS mediates liposome
      internalization by macrophages via a mechanism not affected by HIV-1. Hence, PS
      liposomes mimic apoptotic cells and are internalized into the macrophages due to
      specific recognition, carrying the previously bound HIV-VLPs. With a combination
      of flow cytometry, confocal live-cell imaging and electron microscopy we
      demonstrate that the PS-immunoliposomes presented here are able to elicit
      efficient HIV-VLPs phagocytosis by macrophages and might represent a new
      nanotechnological approach to enhance HIV-1 antigen presentation and reduce the
      ongoing inflammation processes. FROM THE CLINICAL EDITOR: This team of authors
      demonstrate that specific phosphatidylserin immunoliposomes are able to elicit
      efficient phagocytosis of HIV-virus-like particle by macrophages and might
      represent a new nanomedicine approach to enhance HIV-1 antigen presentation and
      reduce ongoing inflammation processes.

PMID- 24589933
TI  - Management of obstructive sleep apnea in adults.

PMID- 24589934
TI  - Unusual exclusion criteria.

PMID- 24589935
TI  - Unusual exclusion criteria.

PMID- 24589936
TI  - Too lazy for primary care.

PMID- 24589937
TI  - A proneural gene controls C. elegans neuroblast asymmetric division and
      migration.
AB  - Proneural genes control the generation of neuroblasts from the neuroepithelium,
      but their functions in neuroblast asymmetric division and migration remain
      elusive. Here, we identified Caenorhabditiselegans mutants of a proneural
      transcription factor (TF) lin-32, in which Q neuroblasts are produced. We showed
      that LIN-32 functions in parallel with a storkhead TF, HAM-1, to regulate Q
      neuroblast asymmetric division, and that Q neuroblast migration is inhibited in
      lin-32 alleles. Consistently, lin-32 is expressed throughout Q neuroblast
      lineage, suggesting that LIN-32 may promote different target gene expression. Our
      studies thus uncovered previously unknown functions of a proneural gene in
      neuroblast development. 

PMID- 24589939
TI  - Bruxism and TMD disorders of everyday dental clinical practice.
AB  - Bruxism, as an etiological factor for the development of TMD, includes different
      disorders of the TMJ and the masticatory muscles, exhibiting pain and disruption
      of the stomatognathic functions. Our goal was to study patients with bruxism and
      TMD from everyday dental clinical practice, in terms of diagnosis, identification
      of etiological factors, classification and treatment of these disorders. We
      treated 120 patients, divided into 2 groups of 60 patients. The first group had
      disorders of the TMJ, and the second of the masticatory muscles. The groups were
      divided into subgroups of 20 patients with dislocation of the articular disk with
      or without reduction and inflammation of TMJ. The second group was organized from
      patients with myofascial pain, myositis and muscular trismus. Our conservative
      treatment consisted of patient education, NSAID, myorelaxants, fabrication of
      prosthetics, repositioning and stabilization splints. The progress of the
      patients was followed immediately after the delivery of the prosthetics and the
      splint, after 1, 6 and 12 months. The results showed that in patients with
      disorders of the TMJ there were visible signs of recovery after 6 months in 68.3%
      patients, and in 85% after 12 months. In the second group we achieved faster
      results with the elimination of symptoms. Patients with afflictions of the
      muscles in 88.3% of cases noticed relief of symptoms even after 6 months and in
      98.3% after 12 months. As therapists we concluded that timely treated
      complications of bruxism and TMD prevent the destruction of the TMJ, masticatory
      muscles and the entire stomatognatic system.

PMID- 24589938
TI  - Comparison of text and video computer-tailored interventions for smoking
      cessation: randomized controlled trial.
AB  - BACKGROUND: A wide range of effective smoking cessation interventions have been
      developed to help smokers to quit. Smoking rates remain high, especially among
      people with a lower level of education. Multiple tailoring adapted to the
      individual's readiness to quit and the use of visual messaging may increase
      smoking cessation. OBJECTIVE: The results of video and text computer tailoring
      were compared with the results of a control condition. Main effects and
      differential effects for subgroups with different educational levels and
      different levels of readiness to quit were assessed. METHODS: During a blind
      randomized controlled trial, smokers willing to quit within 6 months were
      assigned to a video computer tailoring group with video messages (n=670), a text
      computer tailoring group with text messages (n=708), or to a control condition
      with short generic text advice (n=721). After 6 months, effects on 7-day point
      prevalence abstinence and prolonged abstinence were assessed using logistic
      regression analyses. Analyses were conducted in 2 samples: (1) respondents (as
      randomly assigned) who filled in the baseline questionnaire and completed the
      first session of the program, and (2) a subsample of sample 1, excluding
      respondents who did not adhere to at least one further intervention session. In
      primary analyses, we used a negative scenario in which respondents lost to follow
      up were classified as smokers. Complete case analysis and multiple imputation
      analyses were considered as secondary analyses. RESULTS: In sample 1, the
      negative scenario analyses revealed that video computer tailoring was more
      effective in increasing 7-day point prevalence abstinence than the control
      condition (OR 1.45, 95% CI 1.09-1.94, P=.01). Video computer tailoring also
      resulted in significantly higher prolonged abstinence rates than controls among
      smokers with a low (ready to quit within 4-6 months) readiness to quit (OR 5.13,
      95% CI 1.76-14.92, P=.003). Analyses of sample 2 showed similar results, although
      text computer tailoring was also more effective than control in realizing 7-day
      point prevalence abstinence. No differential effects were found for level of
      education. Complete case analyses and multiple imputation yielded similar
      results. CONCLUSIONS: In all analyses, video computer tailoring was effective in
      realizing smoking cessation. Furthermore, video computer tailoring was especially
      successful for smokers with a low readiness to quit smoking. Text computer
      tailoring was only effective for sample 2. Results suggest that video-based
      messages with personalized feedback adapted to the smoker's motivation to quit
      might be effective in increasing abstinence rates for smokers with diverse
      educational levels. TRIAL REGISTRATION: Netherlands Trial Register: NTR3102;
      http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=3102 (Archived by
      WebCite at http://www.webcitation.org/6NS8xhzUV).

PMID- 24589940
TI  - Proton-transfer in hydrogenated guanine-cytosine trimer neutral species, cations,
      and anions embedded in B-form DNA.
AB  - The neutral DNA trimers with the hydrogen atom added to the C8 site of the middle
      guanine-cytosine (GC) base pair, the DNA trimers protonated at the N7 site of the
      middle GC base pair, and the anionic species resulting from hydride addition to
      the C6 site of the middle GC base pair are investigated using theoretical
      methods. The canonical Watson-Crick structures (WC), transition state structures
      (TS) and proton-transferred structures (PT) of each relevant system are optimized
      in the gas phase and in aqueous solution, in order to understand the processes of
      proton transfer. The proton transfer reactions of the DNA trimers are compared
      with the corresponding isolated hydrogenated GC base pairs to explore the
      influence of the surrounding molecules and the base sequence. The proton transfer
      reactions of the neutral species, cations, and anions are compared, aiming to
      clarify the effects of the system's total charge. The results reveal that the
      surrounding molecules decrease the reaction energies of proton-transfer in
      aqueous solution. The structures with the dATGCAT and dGCGCGC sequences
      facilitate proton H4a transfer, but hinder proton H1 transfer. The structures
      with the dCGGCCG and dTAGCTA sequences facilitate proton H1 transfer. The net
      charge on the system plays an important role in determining the single and double
      proton-transfer patterns. Anions are more likely to experience proton-transfer
      reactions than neutral species and cations, and all the proton-transfer reactions
      of the anions are exothermic. 

PMID- 24589941
TI  - Influence of engineered surface on cell directionality and motility.
AB  - Control of cell migration is important in numerous key biological processes, and
      is implicated in pathological conditions such as cancer metastasis and
      inflammatory diseases. Many previous studies indicated that cell migration could
      be guided by micropatterns fabricated on cell culture surfaces. In this study, we
      designed a polydimethylsiloxane cell culture substrate with gratings punctuated
      by corners and ends, and studied its effects on the behavior of MC3T3-E1
      osteoblast cells. MC3T3-E1 cells elongated and aligned with the gratings, and the
      migration paths of the cells appeared to be guided by the grating pattern.
      Interestingly, more than 88% of the cells cultured on these patterns were
      observed to reverse their migration directions at least once during the 16 h
      examination period. Most of the reversal events occurred at the corners and the
      ends of the pattern, suggesting these localized topographical features induce an
      abrupt loss in directional persistence. Moreover, the cell speed was observed to
      increase temporarily right after each directional reversal. Focal adhesion
      complexes were more well-established in cells on the angular gratings than on
      flat surfaces, but the formation of filipodia appeared to be imbalanced at the
      corners and the ends, possibly leading to the loss of directional persistence.
      This study describes the first engineered cell culture surface that consistently
      induces changes in the directional persistence of adherent cells. This will
      provide an experimental model for the study of this phenomenon and a valuable
      platform to control the cell motility and directionality, which can be used for
      cell screening and selection. 

PMID- 24589942
TI  - Catalyst-free tandem Michael addition/decarboxylation of (thio)coumarin-3
      carboxylic acids with indoles: facile synthesis of indole-3-substituted 3,4
      dihydro(thio)coumarins.
AB  - The tandem Michael addition/decarboxylation of (thio)coumarin-3-carboxylic acids
      with indoles has been developed and the biologically important indole-3
      substituted dihydrocoumarins were obtained in good to excellent yields under
      catalyst-free conditions. 

PMID- 24589943
TI  - Antioxidant activity and preventive effect of aqueous leaf extract of Aloe Vera
      on gentamicin-induced nephrotoxicity in male Wistar rats.
AB  - OBJECTIVE: In the present study, the nephroprotective and curative effects of
      aqueous extract of AV on gentamicin-induced tubular toxicity in male Wistar rats
      were investigated. Antioxidant activity, phenolic and flavonoid contents of AV
      were also determined. MATERIALS AND METHODS: In a preclinical study, 60 male
      Wistar rats were designated into 6 groups of 10 and treated as follows: Group I:
      Treated with vehicle (distilled water) and kept as control. Group II: Received
      300 mg/kg/d AV for three days then, AV plus GM (80 mg/kg; intraperitoneally) for
      7 more days and sacrificed. Group III: Received 300 mg/kg AV orally for 10 days,
      then sacrificed. Group IV: Received GM for 7 days and sacrificed. Group V:
      Received GM for 7 days and saline for ten days and sacrificed on 17th day. Group
      VI: Received GM for 7 days, then AV for 10 days and sacrificed. RESULTS: The
      levels of flavonoid and phenolic compounds in Aloe vera extract were 43 +/- 3.8
      mg/g (Rutin equivalent) and 80.1 +/- 3.8 mg/g (Gallic acid equivalent),
      respectively. The antioxidant activity of the extract was 38%. The intensity of
      nephrotoxicity in group 2 that received AV 300 mg/kg/d as prophylaxis was not
      significantly different from the group I and from the group II which treated with
      300 mg/kg/d AV without GM. This finding reveals that AV as prophylaxis could
      potentially attenuate the GM-induced nephrotoxicity. CONCLUSIONS: Aole vera
      significantly protects the renal cells and reduces the severity of tubular damage
      caused by gentamicin. However, it cannot regenerate tubular damage.

PMID- 24589944
TI  - Lamivudine and Adefovir Motif Variants Detected in chronic Hepatitis B patients.
AB  - BACKGROUND AND AIMS: Chronic hepatitis B is an important health problem
      worldwide. Lamivudine, adefovir, entecavir and telbivudine are the oral drugs
      licensed for the treatment of patients with chronic hepatitis B. Implementation
      of antiviral therapy leads to the emergence of mutant strains during the
      treatment in chronic hepatitis B. Primary antiviral resistance may be rarely
      encountered. The aims of this study were to detect the resistance patterns of
      Hepatit B Virus strains in treatment-naive chronic hepatitis B patients.
      MATERIALS AND METHODS: A total of 147 CHB patients were included to this study
      which was carried on between January 2007- December 2010. HBV DNA levels were
      detected by using the Real time PCR (COBAS Ampli- Prep/COBAS TaqMan HBV Test).
      HBV-DNA was extracted from the sera of the patients by using extraction kit
      (Invisorb, Instant Spin DNA/RNA Virus Mini Kit, Germany). A line prob assay (Inno
      Lipa HBV DR v2, Innogenetics N.V, Ghent, Belgium) was used to determine motif
      variants at viral polymerase gene fragment in HBV-DNA samples of these patients
      and evaluated colorimetrically. RESULTS: In 147 patients antiviral resistance
      rate was found 17% (25/147) for lamivudin, 5.44% (8/147) adefovir, 0.68%(1/147)
      lamivudin and adefovir. Various mutations were detected. This mutations;
      responsible for lamivudine resistance YMDD+YVDD (n=10), YMDD+YIDD (n=12), YIDD
      (n=2), YVDD (=1); responsible for adefovir resistance N236T (n=3), A181T (n=5);
      responsible for lamivudine and adefovir resistance YMDD+YIDD+N236T (n=1).
      CONCLUSIONS: As a conclusion, it is thought that drug resistance should be
      followed up regularly, the determination of HBV drug resistance as immediate as
      possible period may be instructive for the treatment and follow-up in CHB
      patients. Although determination of known mutations with Inno Lipa DR v2 method
      is disadvantage, because of ease of application and the determination of both
      lamivudin-adefovir resistance in a short time, it can be used for the treatment
      and follow-up in CHB patients.

PMID- 24589945
TI  - Parkinsonism in elderly rheumatoid arthritis patients.
AB  - OBJECTIVE: The incidences of extrapyramidal symptoms and Parkinson's disease were
      reported to be increased in patients with rheumatoid arthritis (RA). In this
      study we aimed to explore the frequency of the symptoms of Parkinsonism among RA
      patients older than 60 years. PATIENTS AND METHODS: 30 (6 males, 24 females)
      consecutive RA patients, followed at a rheumatology outpatient clinic, who were
      60 years of age or older; 23 patients who were diagnosed as PD and 50 sex and age
      matched healthy controls were included to the study. All participants were
      examined for the motor and non-motor findings of Parkinsonism including
      bradykinesia, rigidity, tremor, postural abnormality, upper limb sway
      abnormality, gait impairment, decrease in facial expression, seborrhea, slowing
      of speech and impairment in the self care. RESULTS: When the RA, PD cases and
      healthy control group were compared for bradykinesia, rigidity, tremor, posture,
      upper limb sway, gait impairment, facial expression, seborrhea, speech and self
      care; highly significant differences were seen for all parameters. Two out of the
      30 RA cases (6,7%) were diagnosed as Parkinson's disease. CONCLUSIONS: The signs
      of Parkinsonism and Parkinson's disease were found more frequent in elderly RA
      cases as compared to healthy controls.

PMID- 24589946
TI  - Factors affecting morbidity and mortality in hollow visceral injuries following
      blunt abdominal trauma.
AB  - BACKGROUND AND AIM: Hollow visceral injuries following blunt abdominal trauma are
      uncommon. The potential risk factors affecting morbidity and mortality are not
      well known. The purpose of our study was to evaluate the outcomes of hollow
      viscus perforation after blunt abdominal trauma. MATERIALS AND METHODS: Patient
      files of 56 adult patients who were treated with diagnosis hollow viscus injuries
      due to blunt abdominal trauma between the years 2000 and 2011 at the Dicle
      University Medical School General Surgery Clinic were retrospectively evaluated
      by analyzing the relationship between morbidity-mortality and potential risk
      factors. RESULTS: Fifty-six patients formed the study group, with median age of
      37.5 +/- 17,0 (range, 16-78) years and a significant male (80.3%) predominance.
      The median Injury Severity Score was 4 (1-25). The median length of hospital stay
      7.5 (1-21) days. The mean age in the group with morbidity (47.1 +/- 17.4) was
      significantly higher than the group without morbidity (34.3 +/- 15.8) (p<0.05).
      Also, re-operation (p=0.0013), treatment modality (p=0.037), cause of injuries
      (0.0046) were other factors that affect morbidity. CONCLUSIONS: These findings
      suggest that factors affecting morbidity were cause of injuries, re-operation and
      treatment in patients with hollow viscus injury caused by blunt abdominal trauma.
      And factors affecting mortality were the injured organ, the presence of shock and
      median injury severity score.

PMID- 24589947
TI  - [Masuda's Central Serous Chorioretinopathy (C.S.C.R.) and its somatic investment
      in Narcissism: our observations on new psychiatric nosography].
AB  - Case report. Co-morbidity between central serous chorioretinopathy (C.R.S.C.) and
      narcissistic personality disorder. A reflection on the importance of an
      integrated approach to this ophthalmological disease through the description of
      its psychosomatic aspects and the evaluation of the nosographic definition in
      psychiatry. The central serous chorioretinopathy (C.R.S.C.) is a transudative
      disease affecting the posterior pole of the eye, that rapidly compromises the
      visual acuity, although it is a self-limited disease. Narcissism is a personality
      disorder characterised by an extreme gratification of self, without actually
      taking care of other people. In the current work both the diseases, along with
      the respective psychosomatic consequences the patient received, are examined. 

PMID- 24589948
TI  - Perianchor radiolucency following PEEK suture anchor application associated with
      recurrent shoulder dislocation: a case report.
AB  - The authors describe a case of a 25 year old male who suffered recurrent shoulder
      dislocations after a symptom-free period following an initial arthroscopic
      shoulder stabilisation using PEEK suture anchors to repair the Bankart and SLAP
      lesions. The MRI and CT scans showed perianchor radiolucency around all of the
      previously placed PEEK suture anchors. It is believed that his recurrent shoulder
      instability was related to this radiological finding although the exact
      pathomechanism of the osteolysis is not clear. To our knowledge, this is the
      first reported case of perianchor radiolucency after the use of a PEEK suture
      anchor. 

PMID- 24589949
TI  - Lambda light chain myeloma with co-migrating paraprotein at beta region on
      agarose gel electrophoresis: a case report.
AB  - Paraproteinemia is one of the diagnostic features of multiple myeloma. A commonly
      used method is the detection of paraprotein by agarose gel electrophoresis (AGE)
      followed by by immunofixation electrophoresis (IFE) to confirm monoclonality. Due
      to their smaller size, immunoglobulin A (IgA) and light chain only paraproteins
      may appear at the beta or even alpha 2 protein fractions. Here, we discuss a case
      report of a 47-year-old man who presented with pathological fracture of third
      thoracic (T3) vertebra. Serum protein electrophoresis (SPE) was initially
      reported as no paraprotein detected. However, a bone biopsy was reported to show
      plasma cell proliferation with light chain restriction. A repeat sample for
      protein electrophoresis together with IFE revealed lambda light chain paraprotein
      co-migrating at the beta region. The beta band plus paraprotein was quantitated
      as 4.3 g/L (7.0%), which was within normal limits of the beta protein fraction.
      Hence, it has to be remembered that if the SPE is negative, it does not
      necessarily mean that the paraprotein is absent in cases which are highly
      suspicious. 

PMID- 24589950
TI  - Malignant melanoma masqueraded as ingrown toe nail.
AB  - We report a case in a 62-year-old female who presented with a year history of
      dull aching pain of the left big toe, which was aggravated by pressure on the
      nail and relieved by analgesia. Tissue biopsy confirmed the diagnosis of
      malignant melanoma. There was a black colour swelling about 3x8 mm in size over
      the medial side of the dorsum of left big toe with a scar of previous operation.
      Histopathological examination showed on gross section of 2 blackish area one
      infiltrate the bone the other the tumour not infiltrate the proximal
      interphalangial joint with another satellite lesion 20mm from main tumour area
      was found. Malignant cells were large with abundant cytoplasm, hyperchromatic
      nuclei and some prominent eosinophilic nucleoli. Melanin pigment was markedly
      seen. The big toe was amputated. We here highlight a case where the patient was
      diagnosed and managed as having ingrown nail of the left big toe while in actual
      fact she had a subungual amelanotic melanoma. 

PMID- 24589951
TI  - [Skeletal muscle: from development to function].
AB  - Aim of this minireview was to focus attention on some aspects of myogenesis,
      differentiation and metabolism of muscle in mammals (rodents and humans), and to
      summarize current knowledge on the issue referring to both our experimental
      contributions and those of other authors.Particular attention was directed at
      both the mesodermal stem cells, elements of the early embryonic period, and the
      regulatory genes. It was also discussed the crucial role of several growth
      factors, such as myogenin and bFGF, and substances of vital importance to the
      regulation of contraction: somatomedins [Insulin-like Growth Factors (IGF-I and
      IGF-II)], interleukin-15 (IL -15), transferrin (Tf), catecholamines (CA). A no
      secondary role in the metabolism of skeletal muscle is played by serotonin (5-HT)
      and its precursor [L-tryptophan (L-Tp)]. The presence of L-Tp, in the diet of
      growing rats, seems to be crucial for protein synthesis and for the increase in
      the number of mitochondria. It has also highlighted the role played by certain
      hormones: growth hormone (GH), thyroid hormones (T3 and T4), sex steroids on
      metabolism, growth and differentiation of skeletal muscle. 

PMID- 24589952
TI  - Elderly gastrointestinal cancer patients and radiochemotherapy: a review.
AB  - Gastrointestinal cancers are among the most frequently occurring cancer
      worldwide. Elderly patients represent a large proportion of patients diagnosed
      with gastrointestinal cancers. Despite this, elderly patients are generally under
      represented in clinical trials, therefore a general consensus on how to treat
      elderly patients is still far from being achieved. In oesophageal cancer,
      radiochemotherapy can be administered successfully and effectively but should be
      administered with close monitoring because of potential toxicities especially
      hematological. In gastric and rectal cancer, there is no clear trade-off between
      efficacy and side effects and some patients may not gain a survival benefit from
      combined treatment. Instead, the treatment of elderly pancreatic cancer patients
      with a good performance status should be no different than the treatment of
      younger patients. Radiochemotherapy maintains its activity and feasibility in
      elderly gastrointestinal cancer patients. Finally, it is very important to assess
      co-morbidity with its severity in order to aid in the development of plans for
      treatment. 

PMID- 24589953
TI  - The predictive role of Paraoxonase 1 (PON1) activity on survival in patients with
      metastatic and nonmetastatic gastric cancer.
AB  - BACKGROUND: Oxidative stress is known to be implicated in the pathogenesis of
      malignancies including gastric cancer (GC). Paraoxonase 1(PON1) is a member of
      antioxidant defense system which acts by hydrolysing peroxidases. Our aim is to
      assess the levels PON1 activity in different stages and localizations of GC and
      analyze the predictive role of PON1 activity on overall survival in GC. MATERIALS
      AND METHODS: One hundred and twenty six patients with GC were enrolled to the
      study. Patients were divided into two groups; group I (nonmetastatic GC, n=65)
      and group II (metastatic GC, n=61). Paraoxonase 1 activity, albumine and lactate
      dehidrogenase levels and whole blood count were analyzed. Union Internationale
      Contre le Cancer system was used for staging procedure. RESULTS: Patients at
      advanced N or M stage have significantly lower levels of PON1 (34.26 U/L and
      29.88 U/L, p=0.04 and p=0.03; respectively). Gender, Lauren's classification,
      grade, localization and T stage of tumor have nonsignificant impact on PON1
      activity. PON1 activity was a significant prognostic factor in GC as well as
      metastasis, localization of tumor and low hemoglobine or albumine level.
      CONCLUSIONS: Lower levels of paraoxonase 1 activity in patients with metastatic
      gastric cancer may reflect the presence of enhanced oxidative stress in advanced
      stages of the disease. PON1 activity is a significant and independent predictor
      of overall survival. Identifying novel prognostic markers can help to establish
      appropriate therapeutic strategies, to determine preventive measures and to
      improve survival rates.

PMID- 24589954
TI  - Which route of antibiotic administration should be used for third molar surgery?
      A split-mouth study to compare intramuscular and oral intake.
AB  - OBJECTIVE: To compare the effectiveness of two different routes of antibiotic
      administration in preventing septic complications in patients undergoing third
      molar extraction. MATERIALS AND METHODS: Twenty-four healthy patients requiring
      bilateral surgical removal of impacted mandibular third molars were successfully
      enrolled for this study. Depth of impaction, angulation, and relationship of the
      lower third molars with the mandibular branch had to be overlapping on both
      sides. A split-mouth design was chosen, so each patient underwent both the first
      and second surgeries, having for each extraction a different antibiotic route of
      administration. The second extraction was carried out 1 month later. To compare
      the effects of the two routes of antibiotic administration, inflammatory
      parameters, such as edema, trismus, pain, fever, dysphagia and lymphadenopathy
      were evaluated 2 and 7 days after surgery. Side effects of each therapy were
      evaluated 48 h after surgery. RESULTS: Oral and intramuscular antibiotic
      therapies overlap in preventing post-operative complications in dental surgery
      (p>0.05), even if the oral intake, seems to promote the onset of significant
      gastrointestinal disorders (p=0.003). CONCLUSIONS: This study could help dentists
      in their ordinary practice to choose the right route of antibiotic administration
      in the third molar surgery. At the same effectiveness, the higher cost and the
      minor compliance of the patient seem not to justify a routine antibiotic
      intramuscular therapy, reserving it for patients with gastrointestinal disorders.

PMID- 24589955
TI  - Use of neutral protamine lispro insulin (NPL) in patients with hyperglycemia
      receiving parenteral nutrition.
AB  - AIMS: Nutritional support with parenteral nutrition (PN), a key component in the
      care of critically ill patients, usually requires insulin therapy in patients
      with diabetes or may require insulin treatment in patients not known to be
      diabetic. We wanted verify whether it is possible to use neutral protamine lispro
      (NPL) in double administration monotherapy in patients receiving artificial
      nutrition (AN) and if the same NPL is capable of obtaining and maintaining
      acceptable glycemic control without inducing hypoglycemia. PATIENTS AND METHODS:
      We studied 18 consecutive patients, who were not taking insulin, they needed to
      start artificial nutrition, and presenting at least two consecutive blood glucose
      > 120 mg/dL. Each patient was given at least 1 U of insulin for every 10 grams of
      glucose infused. RESULTS: Eighteen consecutive patients, not stratified in any
      way, were judged eligible in the last 24 months, with a mean age of 71 years
      (range 54-85 yrs). All patients were evaluated after 2, 3 and 5 days of
      treatment; only 1 patient has not been evaluated to 5 days. Mean glycemic values
      on days 2, 3, 5 were in range between 145 and 180 mg/dL. Any adjustments in NPL
      dose were carried out by the team of nutrition and there was no hypoglycemia that
      required medical intervention in emergency. CONCLUSIONS: Our impression is that
      also lispro protamine insulin (NPL) in double subcutaneous administration may
      contribute to improving the glycemic values in patients receiving parenteral
      nutrition with hyperglycemia.

PMID- 24589956
TI  - Is nasal packing required in epistaxis?
AB  - OBJECTIVE: To demonstrate the efficacy of identification of bleeding source with
      nasal endoscopy and cauterization (bipolar or radiofrequency) without nasal
      packing in adults with posterior epistaxis unable to be treated with nasal
      packing. MATERIALS AND METHODS: The average age of patients was 56.16 +/- 12.6
      (38-72) years, and female-male ratio was 1/5. The average systolic blood pressure
      was found to be 150 +/- 30, while diastolic blood pressure was 90 +/- 20 mmHg.
      Average hemoglobin concentration was 11.2 +/- 3.1 (7-15). The bleeding was on the
      left side in 8 patients and on the right in 4 patients. Probable etiology was
      considered hypertension crisis (33.3%), use of nasal steroids (8.3%), nasal
      surgery (8.3%), however in half (50%) of the cases the cause was unidentified. Of
      the cases, 6 had hypertension, 4 COPD, 10 tobacco use and 5 alcohol use. The
      source of epistaxis was anterior ethmoidal artery in 2 cases and spheopalatine
      artery in 10 cases. Two of the cases were treated with radiofrequency
      coagulation, and ten with bipolar cauterization. Only one of the cases was
      administered 2 units of packed red blood cells, and one of the cases had
      postoperative recurrent bleeding. The patients were hospitalized in average 3.2
      (2-5) days and no reccurence of hemorrhage was seen in 3 month follow up.
      CONCLUSIONS: Dundee epistaxis menagement protocol described by Barnes and
      Spielman may be applied in adults. Endoscopical detection of the bleeding site
      and cauterizing the arterial feed source is highly successful in the treatment.
      Nasal packing may more commonly lead to complication especially in the elderly
      and in patients with heart and respiratory problems.

PMID- 24589957
TI  - Short-term functional outcomes of a delayed single-stage reconstruction of
      chronic posterior cruciate ligament and posterolateral corner deficiency.
AB  - AIMS: To evaluate the functional outcomes of a delayed (>6 months post-injury)
      and combined reconstruction of grade III posterior cruciate ligament (PCL) and
      grade III posterolateral corner (PLC) deficiencies. PATIENTS AND METHODS: Between
      March 2006 and October 2009, a delayed surgery consisting of arthroscopically
      assisted PCL reconstruction and open reconstruction of the PLC was performed on
      19 men and 2 women (average age, 29 years). The mean time-to-surgery was 18
      months (range, 7-51 months) and duration of follow-up was 22 months (range, 12-48
      months). Postoperatively, patients were evaluated using Lysholm score, Tegner
      activity score, and International Knee Documentation Committee (IKDC) subjective
      and objective scores. RESULTS: At the final follow-up, majority of the knees
      (61.9%) achieved either normal or nearly normal rating objective IKDC score. The
      means of IKDC subjective score, Lysholm score and Tegner activity level were
      62.09, 74.35 and 5.14 respectively. One patient was able to participate in
      competitive sport, 5 patients were able to be involved in recreational sports for
      at least 5 times per week, 10 patients were able to perform heavy labour and
      recreational sports for at least twice weekly, 4 patients were able to engage in
      moderately heavy labour work and one patient was only able to perform light
      labour work. There was no significant statistical association found between the
      time-to-surgery and the final patients' outcomes. CONCLUSIONS: A delayed
      simultaneous reconstruction of chronic grade III PCL and PLC deficiencies can
      restore sufficient function for standard daily and recreational sports activities
      to the patients.

PMID- 24589958
TI  - Serum amyloid A and Omentin levels in acute appendicitis: a preliminary study for
      a novel diagnostic approach.
AB  - BACKGROUND: The diagnosis of acute appendicitis is based on medical history and
      physical examination. Serum (S) amiloid A (AA) levels are elevated in many
      inflammatory conditions. Omentin is a recently discovered adipokine showing
      decreased levels associated with inflammatory conditions. We aimed to measure SAA
      and omentin levels in patients with acute appendicitis. MATERIALS AND METHODS: 36
      patients with a diagnosis of acute appendicitis and 30 healthy subjects were
      enrolled to this research study. A statistical analysis was performed using IBM
      SPSS Statistics Version 16.0 (SPSS Inc.(r), Chicago, IL, United States). RESULTS:
      Patients in study group were significantly older than healthy control subjects
      (p=0.013). Body mass index of the patients with acute appendicitis (23.2 +/- 1.3)
      was greater than that of the control group (22.7 +/- 1), but the difference did
      not reach the statistically significance (p=0.076). ). Mean level of SAA was
      significantly raised in study group compared to healthy control subjects (p<
      0.001). Mean omentin level was significantly lower in study group compared to
      healthy subjects (p=0.013). CONCLUSIONS: In conclusion, although diagnosis of
      acute appendicitis is mostly based on clinical findings, omentin and especially
      SAA measurement in serum may help surgeons to avoid negative laparatomy.

PMID- 24589959
TI  - Comparable down-regulation of TYR, TYRP1 and TYRP2 genes and inhibition of
      melanogenesis by tyrostat, tocotrienol-rich fraction and tocopherol in human skin
      melanocytes improves skin pigmentation.
AB  - BACKGROUND AND OBJECTIVE: Antioxidant has been recognized to inhibit UV-induced
      melanogenesis. This study aimed to elucidate the molecular mechanism of tyrostat,
      tocopherol and tocotrienol-rich fraction in inhibiting melanogenesis in human
      skin melanocytes. MATERIALS AND METHODS: Primary culture of melanocytes was
      exposed to repeated doses of 0.6 J/cm2 UVA for 6 days and treated with tyrostat,
      tocotrienol-rich fraction or tocopherol alone or in combination. RESULTS: UVA
      irradiation increased melanin content and tyrosinase activity and up-regulated
      TYR, TYRP1 and TYRP2 genes. Treatment with tyrostat, tocotrienol-rich fraction or
      tocopherol decreased melanin content and down-regulated TYR, TYRP1 and TYRP2
      genes with decreased tyrosinase activity. Combined treatment exerted better
      effects as compared to treatment with single compound in decreasing the melanin
      content and down-regulating TYR, TYRP1 and TYRP2 genes. These findings indicated
      that tyrostat, tocotrienol-rich fraction and tocopherol inhibit melanogenesis by
      modulating the expression of genes involved in the regulation of melanin
      synthesis and inhibiting tyrosinase activity. CONCLUSIONS: Tyrostat, tocopherol
      and tocotrienol-rich fraction possessed anti-melanogenic properties and might be
      useful in improving skin pigmentation caused by UVA exposure.

PMID- 24589960
TI  - Investigation of the relationship between non-alcoholic fatty liver disease and
      coronary artery disease.
AB  - AIMS: The purpose of the study was to examine the association between visceral
      adiposity form of non-alcoholic fatty liver and coronary artery disease severity
      and also to investigate the relationship between the epicardial adipose tissue
      thickness and non-alcoholic fatty liver disease with clinical and anthropometric
      measurements. MATERIALS AND METHODS: This study included 105 patients (mean age
      of patients were 57 +/- 11, 82 of them male) who were hospitalized for coronary
      angiography because of chest pain. Nonalcoholic fatty liver disease was
      investigated by using ultrasonography. Thickness of the epicardial adipose tissue
      was measured by transthorasic echocardiography to right ventricular free wall
      adjacent to the parasternal long and short axis images. Gensini score was used
      for the severity of coronary artery disease. RESULTS: In patients with non
      alcoholic fatty liver disease, right ventricular free wall epicardial adipose
      tissue thickness average of parasternal long and short axis were thicker than
      those who do not have non alcholic fatty liver disease (0,90 +/- 0,19 cm; 0.58 +/
      0.18 cm, p<0.001). Also, in patients with severe coronary artery disease, right
      ventricular free wall parasternal long and short axis average thickness of
      epicardial fat tissue was thicker than those of patients without severe coronary
      stenosis (0.86 +/- 0.21 cm; 0,66 +/- 0.26 cm, p=0.001). For predictability of
      coronary artery disease, Receiver Operating Characteristic analysis of the area
      under the curve was found to be 0.60 (50.2 to 74.7, 95% Confidence Limits).
      CONCLUSIONS: Not only the fatty tissue which surrounds the heart effects the
      coronary arteries but also other visceral organs adiposity effects the coronary
      arteries atherosclerotic process.

PMID- 24589962
TI  - The prevalence of asthma and allergic diseases among adults 30-49 years of age in
      Bolu, Western Black Sea Region of Turkey.
AB  - AIMS: To determine the prevalence of asthma, asthma-like symptoms and allergic
      diseases among adults 30-49 years of age in regions of Bolu. MATERIALS AND
      METHODS: A questionnaire was given to families of students in schools in
      different areas of Bolu, Turkey. The European Community Respiratory Health Survey
      (ECRHS) and a questionnaire, including questions about the socioeconomic status
      and demographic characteristics of the participants, were responded to by 1403
      people. RESULTS: The prevalence of symptoms and diseases were as follows:
      wheezing in the last year 12.0% (n=168), asthma 8.7% (n=121), doctor-diagnosed
      asthma 3.6% (n=50), currently taking drugs for asthma 1.2% (n=17), allergic
      rhinitis 16.5% (n=230), and eczema 9.6% (n=134). The risk factors for each
      symptom or disease were as follows: for wheezing: smoking in the house (odds
      ratio [OR]=2.43 and 95% Confidence Limits [95%CL]=1.53-3.86), living in a non
      concrete building (OR=2.17, 95%CL=1.27-3.69); for asthma: mold in the house
      (OR=1.70, 95% CL=1.05-2.76), living in a shanty (OR=2.76, 95%CL=1.30-5.85),
      smoking in the house (OR=1.51, 95%CL=1.02-2.22); for allergic rhinitis: being
      female (OR=1.55, 95%CL=1.08-2.24), living in a shanty (OR=5.81, 95%CL=2.06
      16.39), a monthly income below $300 (OR = 1.74, 95%CL=1.13-2.69). CONCLUSIONS: A
      high rate of undiagnosed and untreated people with asthma among adults 30-49
      years of age is present in Bolu. Especially, while a low socioeconomic level was
      observed to increase the risk of asthma and allergic rhinitis, risk of wheeze and
      asthma was found to be elevated by smoking in house.

PMID- 24589961
TI  - Relationship between fluid status as assessed by bioimpedance analysis and NT-pro
      BNP, blood pressure and left ventricular mass index in hemodialysis patients.
AB  - AIMS: Maintenance of fluid status within an optimal range and accurate assessment
      of dry weight (DW) is essential in patients on intermittent haemodialysis (HD)
      treatment. In this study, we aimed to investigate the association of fluid status
      measured by bioimpedance analysis (BIA) with N-terminal pro-B natriuretic peptide
      (NT-proBNP), blood pressure and left ventricular mass index (LVMI) in
      hemodialysis patients. MATERIALS AND METHODS: A total of 45 hemodialysis patients
      were enrolled in the study. N-terminal pro-B natriuretic peptide (NT-proBNP) was
      measured by immunoassay. Blood pressure (BP) was recorded. Echocardiographic
      examinations were performed in all patients. Multifrequency bioimpedance analysis
      was used to assess pre- and post-dialysis fluid status. Overhydration/
      extracellular water (OH/ECW) ratio was used as fluid status index and OH/ECW
      ratio >0.15 was defined as clinical overhydration. Patients were divided into two
      groups; overhydrated (OH/ECW>0.15) and non-overhydrated (OH/ECW<=0.15). RESULTS:
      OH/ECW, systolic blood pressure (SBP), diastolic blood pressure (DBP), LVMI and
      NT-proBNP levels were significanly reduced after hemodialysis session. The
      presence of overhydration was more frequent in pre-HD patients compared to post
      HD patients (31.1% vs 13.3%, p=0.004). OH/ECW was positively correlated with pre
      and post-HD SBP, DBP, LVMI and NT-proBNP (p<0.05). Overhydrated patients had
      significantly higher values of pre-HD and post-HD SBP, DBP, LVMI and NT-proBNP
      compared to non-overhydrated patients. In addition, SBP, DBP, LVMI and NT-proBNP
      levels were significantly reduced after hemodialysis in both overhydrated and non
      overhydrated patients group. CONCLUSIONS: This study revealed that OH/ECW ratio
      was significantly associated with SBP, DBP, LVMI and NT-proBNP.

PMID- 24589963
TI  - The evaluation of carotid intima-media thickness and visceral obesity as an
      atherosclerosis predictor in newly-diagnosed polycystic ovary syndrome.
AB  - PURPOSE: Polycystic ovary syndrome (PCOS) is a common endocrine disorder which is
      associated with multiple risk factors for atherosclerosis. The aim of this study
      was to investigate the CIMT which is used in the early diagnosis of
      atherosclerosis and visceral obesity by ultrasound in newly diagnosed polycystic
      ovary syndrome with normal body mass index. MATERIALS AND METHODS: A case-control
      study was conducted on 25 PCOS women (18-30 years of age) and 25 controls. BMI
      was matched volunteer controls. Carotid intima media thickness (CIMT) and fat
      distribution as visceral fat thickness (VFT) with subcutaneous fat thickness
      (SFT) were measured by ultrasound. After, visceral fat ratio (VFR) fat ratio
      (VFR) was calculated using VFT divided by SFT. The variables were compared using
      the chi(2)-test and Student's t test. RESULTS: Comparing women with PCOS to the
      control group showed that CIMT was similar in both groups (p=0.84). The VFT in
      the PCOS group was higher than the control group (p=0.048). Whereas, the SFT was
      higher in the control group when compared to women with PCOS (p=0.007). The VFR
      was significantly higher in women with PCOS when compared to the control group
      (1.12 +/- 0.38 vs. 0.81 +/- 0.34; p=0.005). CONCLUSIONS: CIMT which used as early
      atherosclerosis predictors have not increased in newly diagnosed PCOS women. Body
      fat distribution was observed in visceral area in the newly diagnosed PCOS women.
      VFR follow up may provide benefit as a quantitative method for the assessment and
      follow up of visceral obesity in women with PCOS.

PMID- 24589964
TI  - Regulatory policies in paediatric research: how harmonised are the ethical
      principles?
AB  - Trials involving children generate considerable practical problems of a mainly
      ethical nature. While there is wide-ranging agreement on the basic ethical
      requisites for these trials, substantial--and even profound--differences remain
      between national and international regulatory policies. For the European Union
      Directive 2001/20/EC is the basic reference for national regulations regarding
      clinical trials. Article 4 of this Directive deals with trials on minors. The
      present article compares the regulations of this Article with four other
      documents regulating paediatric trials in Europe, the US and Japan. This
      comparison points to different approaches relating particularly to: risk
      acceptability, risk/benefit assessments, informed consent, assent of minors.

PMID- 24589965
TI  - Patient with chest pain refractory to proton pump inhibitor: report of a case of
      eosinophilic esophagitis.
AB  - Eosinophilic esophagitis (EoE) is the most common form of gastrointestinal
      disorders associated with eosinophilia. Typically, an inappropriate accumulation
      of eosinophils is found in the esophageal mucosa. EoE can be well managed and
      treated with several options that include an elimination diet, drug therapy (oral
      and topical steroids) and esophageal dilatations. We herein, report a case of a
      49-year-old male affected by EoE associated to chest pain, treated with proton
      pump inhibitor without clinical response. The patient suffered from long lasting
      postprandial fullness and gastroesophageal reflux disease-like symptoms. He had a
      history of episodic asthmatic attacks and allergic rhinitis but had not dysphagia
      or food impaction. The patient recovered completely after an adequate treatment. 

PMID- 24589966
TI  - Lattice Corneal Dystrophy: a report of two cases in twin sisters due to 3
      mutations (T1620C, C1416T, A1924G) in the TGFBI (BIGH3) gene.
AB  - Phenotypic characteristics associated with mutations in the transforming growth
      factor beta-induced (TGFBI) gene in two twin sisters suffering from lattice
      corneal dystrophy are reported. Genomic DNA was extracted from peripheral blood
      and 3 new mutations in association with exons 11-12-14 of the TGFBI gene were
      found. 

PMID- 24589967
TI  - Benign pneumoperitoneum after percutaneous endoscopic gastrostomy (PEG) feeding
      tube placement: do not be afraid!
AB  - In order to ensure enteral feeding, placement of a percutaneous endoscopic
      gastrostomy (PEG) is considered a standard care for patients with oropharyngeal
      malignancies. Benign pneumoperitoneum is a complication of PEG feeding tube
      placement and it is usually an incidental finding that arises, generally,
      immediately following the procedure. We report a case of a benign
      pneumoperitoneum, developed 48 hours after the procedure, which was treated
      conservatively. 

PMID- 24589968
TI  - [Internet use in clinical trials].
AB  - Recruiting patients is a critical point of today's clinical research and, along
      the years, several solutions have been proposed, even if their efficacy seems to
      be doubtful. On the other hand, nowadays, Internet represents a great opportunity
      for improving clinical trial recruitments. Nevertheless, on-line recruitment
      services (e-recruitment) could ensure some advantages (such as facilitating
      interaction between supply and demand of clinical research, time and money
      savings/optimizations, data entry errors reduction), but also raise some issues
      (such as those related to sampling, information, consent, real identity of
      participants and risks for data breaches). The article debates on the
      difficulties to recruit patients for clinical research, in general, and e
      recruitment particularly, discussing some ethical issues raised by internet
      enrolment. 

PMID- 24589969
TI  - Vacuolar cell death in plants: Metacaspase releases the brakes on autophagy.
AB  - Vacuolar programmed cell death (PCD) is indispensable for plant development and
      is accompanied by a dramatic growth of lytic vacuoles, which gradually digest
      cytoplasmic content leading to self-clearance of dying cells. Our recent data
      demonstrate that vacuolar PCD critically requires autophagy and its upstream
      regulator, a caspase-fold protease metacaspase. Furthermore, both components lie
      downstream of the point of no return in the cell-death pathway. Here we consider
      the possibilities that i) autophagy could have both cytotoxic and cytoprotective
      roles in the vacuolar PCD, and ii) metacaspase could augment autophagic flux
      through targeting an as yet unknown autophagy repressor.

PMID- 24589971
TI  - Multi-step inhibition against HIV lifecycle-underlying the "magic" of protease
      inhibitors.

PMID- 24589970
TI  - Production of inflammatory cytokines in response to diphtheria-pertussis-tetanus
      (DPT), haemophilus influenzae type b (Hib), and 7-valent pneumococcal (PCV7)
      vaccines.
AB  - Haemophilus influenzae type b (Hib) and 7-valent pneumococcal (PCV7) vaccines
      both became recommended in Japan in 2010. In this study, cytokine production was
      investigated in peripheral blood mononuclear cells (PBMCs) cultures stimulated
      with diphtheria and tetanus toxoids combined with acellular pertussis vaccine
      (DPT), Hib, and PCV7 separately or concurrent different combinations, all as
      final off-the-shelf vaccines without the individual vaccine components as
      controls. Higher IL-1beta levels were produced when cultures were stimulated with
      PCV than with DPT or Hib, and the concurrent stimulation including PCV7 enhanced
      the production of IL-1beta. Although Hib induced higher levels of IL-6, no
      significant difference was observed in IL-6 production with the concurrent
      stimulation. The concurrent stimulation with Hib/PCV7 and DPT/Hib/PCV7 produced
      higher levels of TNF-alpha and human G-CSF. Cytokine profiles were examined in
      serum samples obtained from 61 vaccine recipients with febrile reactions and 18
      recipients without febrile illness within 24 h of vaccination. No significant
      difference was observed in cytokine levels of IL-1beta, IL-4, IL-6, IL-10, IL-12,
      IFN-gamma, MIP-1, TNF-alpha, and prostaglandin E2 (PGE2) in sera between the two
      groups. However, significantly higher levels of human G-CSF were observed in
      recipients with febrile illness than in those without febrile reactions. Further
      investigations of the significance of elevated serum G-CSF levels are required in
      vaccine recipients with febrile illness. 

PMID- 24589972
TI  - New promises for hepatitis C cure in HIV coinfection.

PMID- 24589973
TI  - Bone marrow transplant to fight cancer and HIV infection.

PMID- 24589974
TI  - New IDSA guidelines for vaccination of immunocompromised patients.

PMID- 24589975
TI  - HIV drug resistance testing still important.

PMID- 24589976
TI  - Spin crossover intermediate plateau stabilization in a flexible 2-D Hofmann-type
      coordination polymer.
AB  - The abrupt and hysteretic two-step spin crossover in a new triazole-based 2-D
      Hofmann-type complex shows a record breaking 120 K intermediate plateau (IP)
      region stabilized by negative cooperative interactions. 

PMID- 24589978
TI  - Treatment of hypothyroidism and psychosis.

PMID- 24589979
TI  - Unemployment and psychosocial outcomes to age 30: A fixed-effects regression
      analysis.
AB  - OBJECTIVE: We aimed to examine the associations between exposure to unemployment
      and psychosocial outcomes over the period from 16 to 30 years, using data from a
      well-studied birth cohort. METHODS: Data were collected over the course of the
      Christchurch Health and Development Study, a longitudinal study of a birth cohort
      of 1265 children, born in Christchurch in 1977, who have been studied to age 30.
      Assessments of unemployment and psychosocial outcomes (mental health, substance
      abuse/dependence, criminal offending, adverse life events and life satisfaction)
      were obtained at ages 18, 21, 25 and 30. RESULTS: Prior to adjustment, an
      increasing duration of unemployment was associated with significant increases in
      the risk of all psychosocial outcomes. These associations were adjusted for
      confounding using conditional, fixed-effects regression techniques. The analyses
      showed significant (p < 0.05) or marginally significant (p < 0.10) associations
      between the duration of unemployment and major depression (p = 0.05), alcohol
      abuse/dependence (p = 0.043), illicit substance abuse/dependence (p = 0.017),
      property/violent offending (p < 0.001), arrests/convictions (p = 0.052), serious
      financial problems (p = 0.007) and life satisfaction (p = 0.092). To test for
      reverse causality, the fixed-effects regression models were extended to include
      lagged, time-dynamic variables representing the respondent's psychosocial burden
      prior to the experience of unemployment. The findings suggested that the
      association between unemployment and psychosocial outcomes was likely to involve
      a causal process in which unemployment led to increased risks of adverse
      psychosocial outcomes. Effect sizes were estimated using attributable risk;
      exposure to unemployment accounted for between 4.2 and 14.0% (median 10.8%) of
      the risk of experiencing the significant psychosocial outcomes. CONCLUSIONS: The
      findings of this study suggest that exposure to unemployment had small but
      pervasive effects on psychosocial adjustment in adolescence and young adulthood.

PMID- 24589980
TI  - Systematic meta-analysis of outcomes associated with psychosis and co-morbid
      substance use.
AB  - OBJECTIVE: To compare the symptoms and social function of patients with psychosis
      and current substance use to those with psychosis and no history of substance
      use. METHOD: The databases EMBASE, MEDLINE and PsycINFO were searched for peer
      reviewed publications in English that reported the characteristics of patients
      with psychotic illness who were current substance users and those who had never
      used substances. The searches yielded 22 articles that met the inclusion
      criteria. Meta-analysis was used to compare four key outcome variables: positive
      symptoms, negative symptoms, depression and social function - and three secondary
      outcomes: violence, self-harm and hospital admissions. RESULTS: Current substance
      using patients were significantly younger than non-substance-using patients and
      were more likely to be male, but did not differ in age at onset of psychosis or
      in their level of education. Current substance users had higher ratings of
      positive symptoms and were more likely to have a history of violence. Older
      studies reported a stronger association between current substance use and
      positive symptoms than more recently published studies. Current substance users
      did not differ from non-users on measurements of negative symptoms, depressive
      symptoms, social function, self-harm, or the number of hospital admissions.
      CONCLUSION: Current substance users with psychosis may have more severe positive
      symptoms than patients who have never used substances, but this result should be
      interpreted with caution because of demographic differences between substance
      users and non-substance users.

PMID- 24589981
TI  - Management of suicidal behaviour: is the world upside down?

PMID- 24589982
TI  - Communicating hydrocephalus with reversible cognitive impairment.

PMID- 24589983
TI  - Simulation of the phase diagram of magnetic vortices in two-dimensional
      superconductors: evidence for vortex chain formation.
AB  - We study the superconducting vortex states induced by the interplay of long-range
      Pearl repulsion and short-range intervortex attraction using Langevin dynamics
      simulations. We show that at low temperatures the vortices form an ordered
      Abrikosov lattice both in low and high fields. The vortices show distinctive
      modulated structures at intermediate fields depending on the effective
      intervortex attraction: ordered vortex chain and kagome-like vortex structures
      for weak attraction; bubble, stripe and antibubble lattices for strong
      attraction. Moreover, in the regime of the chain state, the vortices display
      structural transitions from chain to labyrinthine (or disordered chain) and/or to
      disordered states depending on the strength of the disorder. 

PMID- 24589984
TI  - Color reflectance fiber bundle endomicroscopy without back-reflections.
AB  - Coherent fiber imaging bundles can be used as passive probes for reflectance-mode
      endomicroscopy providing that the back-reflections from the fiber ends are
      efficiently rejected. We describe an approach specific to widefield
      endomicroscopy in which light is injected into a leached fiber bundle near the
      distal end, thereby avoiding reflections from the proximal face. We use this
      method to demonstrate the color widefield reflectance endomicroscopy of ex vivo
      animal tissue.

PMID- 24589985
TI  - Differential diagnosis of nonmelanoma pigmented skin lesions based on harmonic
      generation microscopy.
AB  - In vivo harmonic generation microscopy (HGM) has been applied successfully in
      healthy human skin and can achieve a submicron resolution, similar to
      histopathologic examination, even at a penetration depth up to 270 MUm. This
      study aims to investigate the clinical applicability of HGM imaging for
      differential diagnosis of nonmelanoma pigmented skin lesions. A total of 42
      pigmented skin tumors, including pigmented basal cell carcinoma, melanocytic
      nevus, and seborrheic keratosis were evaluated by HGM ex vivo or in vivo. Based
      on the standard histopathologic characteristics, we established the corresponding
      HGM imaging criteria for each pigmented tumor. Diagnostic performance of HGM for
      differentiating nonmelanoma pigmented skin tumors was evaluated through the
      observers' direct general assessment (overall evaluation) or the presence of two
      imaging criteria with the highest sensitivity and specificity (major criteria
      evaluation). Our results show that, based on the direct general assessment, the
      sensitivity is 92% [95% confidence interval (CI): 67 to 97%] and the specificity
      is 96% (95% CI: 83 to 99%); by major criteria evaluation, 94% sensitivity (95%
      CI: 70 to 99%) and 100% specificity (95% CI: 87 to 100%) are achieved. Our study
      indicates that HGM serves as a promising histopathological examination tool for
      noninvasive differential diagnostics of nonmelanoma pigmented skin tumors.

PMID- 24589977
TI  - Pediatric low-grade gliomas: how modern biology reshapes the clinical field.
AB  - Low-grade gliomas represent the most frequent brain tumors arising during
      childhood. They are characterized by a broad and heterogeneous group of tumors
      that are currently classified by the WHO according to their morphological
      appearance. Here we review the clinical features of these tumors, current
      therapeutic strategies and the recent discovery of genomic alterations
      characteristic to these tumors. We further explore how these recent biological
      findings stand to transform the treatment for these tumors and impact the
      diagnostic criteria for pediatric low-grade gliomas. 

PMID- 24589986
TI  - Integrated photoacoustic, confocal, and two-photon microscope.
AB  - The invention of green fluorescent protein and other molecular fluorescent probes
      has promoted applications of confocal and two-photon fluorescence microscopy in
      biology and medicine. However, exogenous fluorescence contrast agents may affect
      cellular structure and function, and fluorescence microscopy cannot image
      nonfluorescent chromophores. We overcome this limitation by integrating optical
      resolution photoacoustic microscopy into a modern Olympus IX81 confocal, two
      photon, fluorescence microscope setup to provide complementary, label-free,
      optical absorption contrast. Automatically coregistered images can be generated
      from the same sample. Imaging applications in ophthalmology, developmental
      biology, and plant science are demonstrated. For the first time, in a familiar
      microscopic fluorescence imaging setting, this trimodality microscope provides a
      platform for future biological and medical discoveries.

PMID- 24589987
TI  - Calibration-free absolute quantification of particle concentration by statistical
      analyses of photoacoustic signals in vivo.
AB  - Currently, laser fluence calibration is typically required for quantitative
      measurement of particle concentration in photoacoustic imaging. Here, we present
      a calibration-free method to quantify the absolute particle concentration by
      statistically analyzing photoacoustic signals. The proposed method is based on
      the fact that Brownian motion induces particle count fluctuation in the detection
      volume. If the count of particles in the detection volume is assumed to follow
      the Poisson distribution, its expected value can be calculated by the
      photoacoustic signal mean and variance. We first derived a theoretical model for
      photoacoustic signals. Then, we applied our method to quantitative measurement of
      different concentrations of various particles, including red blood cells.
      Finally, we performed in vivo experiments to demonstrate the potential of our
      method in biological applications. The experimental results agreed well with the
      predictions from the theoretical model suggesting that our method can be used for
      noninvasive measurement of absolute particle concentrations in deep tissue
      without fluence calibration.

PMID- 24589988
TI  - Implementing the ban on smoking in Israeli pubs: measuring airborne nicotine and
      enforcement by local authorities.
AB  - BACKGROUND: In 2007 an amendment to the law restricting smoking in pubs and bars
      (P&Bs) was enacted in Israel. However, a year after the ban only slight decreases
      in airborne smoke in P&Bs in one city have been reported. PURPOSE: We aimed to
      assess levels of airborne nicotine in Israeli P&Bs and to measure ifself-reported
      enforcement of the law by local officials was associated with levels of airborne
      nicotine in P&Bs. METHODS: Airborne nicotine levels were measured in 72 P&Bs in
      29 towns in Israel; this consisted of 90% of eligible towns. In addition, 73
      local authority officials were interviewed in 25 of these towns. The officials
      were asked to assess the local authority's level of enforcement of the law
      banning smoking in P&Bs. The association of levels of airborne nicotine with the
      levels of enforcement of the law was calculated. Data were collected during 2009
      2010 and analyzed in 2010-2011. RESULTS: Levels of airborne nicotine were
      comparatively high in P&Bs. No association was detected between levels of
      nicotine and the P&Bs' characteristics. In the larger towns, levels of airborne
      nicotine were higher. In 16% of towns the local authority officials reported high
      levels of law enforcement. Generally, levels of reported enforcement by local
      authorities were low and did not predict levels of airborne nicotine in the P&Bs.
      CONCLUSIONS: Self-reported local authorities' law enforcement was not associated
      with levels of airborne nicotine in P&Bs in these towns. There is a need to
      develop ways to increase law enforcement by the local authorities or other
      agencies.

PMID- 24589989
TI  - Experience Corps Baltimore: Exploring the Stressors and Rewards of High-intensity
      Civic Engagement.
AB  - PURPOSE: Experience Corps (EC) represents a high-intensity, intergenerational
      civic engagement activity where older adults serve as mentors and tutors in
      elementary schools. Although high-intensity volunteer opportunities are designed
      to enhance the health and well being of older adult volunteers, little is known
      about the negative and positive aspects of volunteering unique to
      intergenerational programs from the volunteer's perspective. DESIGN AND METHODS:
      Stressors and rewards associated with volunteering in EC were explored in 8 focus
      group discussions with 46 volunteers from EC Baltimore. Transcripts were coded
      for frequently expressed themes. RESULTS: Participants reported stressors and
      rewards within 5 key domains: intergenerational (children's problem behavior,
      working with and helping children, observing/facilitating improvement or
      transformation in a child, and developing a special connection with a child);
      external to EC (poor parenting and children's social stressors); interpersonal
      (challenges in working with teachers and bonding/making social connections);
      personal (enjoyment, self-enhancement/achievement, and being/feeling more
      active); and structural (satisfaction with the structural elements of the EC
      program). IMPLICATIONS: Volunteers experienced unique intergenerational stressors
      related to children's problem behavior and societal factors external to the EC
      program. Overall, intergenerational, interpersonal, and personal rewards from
      volunteering, as well as program structure may have balanced the stress
      associated with volunteering. A better understanding of stressors and rewards
      from high-intensity volunteer programs may enhance our understanding of how
      intergenerational civic engagement volunteering affects well being in later life
      and may inform project modifications to maximize such benefits for future
      volunteers and those they serve.

PMID- 24589990
TI  - Sexual dimorphism in white and brown adipose tissue with obesity and
      inflammation.
AB  - This article is part of a Special Issue "Energy Balance". Obesity and its
      associated comorbidities remain at epidemic levels globally and show no signs of
      abatement in either adult or child populations. White adipose tissue has long
      been established as an endocrine signalling organ possessing both metabolic and
      immune functions. This role can become dysregulated following excess adiposity
      caused by adipocyte hypertrophy and hyperplasia. In contrast, brown adipose
      tissue (BAT) is only present in comparatively small amounts in the body but can
      significantly impact on heat production, and thus could prevent excess white
      adiposity. Obesity and associated risk factors for adverse metabolic health are
      not only linked with enlarged fat mass but also are dependent on its anatomical
      deposition. In addition, numerous studies have revealed a disparity in white
      adipose tissue deposition prior to and during the development of obesity between
      the sexes. Females therefore tend to develop a greater abundance of femoral and
      gluteal subcutaneous fat whereas males exhibit more central adiposity. In
      females, lower body subcutaneous adipose tissue depots appear to possess a
      greater capacity for lipid storage, enhanced lipolytic flux and hyperplastic
      tissue remodelling compared to visceral adipocytes. These differences are
      acknowledged to contribute to the poorer metabolic and inflammatory profiles
      observed in males. Importantly, the converse outcomes between sexes disappear
      after the menopause, suggesting a role for sex hormones within the onset of
      metabolic complications with obesity. This review further considers how BAT
      impacts upon on the relationship between excess adiposity, gender, inflammation
      and endocrine signalling and could thus ultimately be a target to prevent
      obesity. 

PMID- 24589991
TI  - The role of the pineal gland in the photoperiodic control of bird song frequency
      and repertoire in the house sparrow, Passer domesticus.
AB  - Temperate zone birds are highly seasonal in many aspects of their physiology. In
      mammals, but not in birds, the pineal gland is an important component regulating
      seasonal patterns of primary gonadal functions. Pineal melatonin in birds instead
      affects seasonal changes in brain song control structures, suggesting the pineal
      gland regulates seasonal song behavior. The present study tests the hypothesis
      that the pineal gland transduces photoperiodic information to the control of
      seasonal song behavior to synchronize this important behavior to the appropriate
      phenology. House sparrows, Passer domesticus, expressed a rich array of
      vocalizations ranging from calls to multisyllabic songs and motifs of songs that
      varied under a regimen of different photoperiodic conditions that were simulated
      at different times of year. Control (SHAM) birds exhibited increases in song
      behavior when they were experimentally transferred from short days, simulating
      winter, to equinoctial and long days, simulating summer, and decreased
      vocalization when they were transferred back to short days. When maintained in
      long days for longer periods, the birds became reproductively photorefractory as
      measured by the yellowing of the birds' bills; however, song behavior persisted
      in the SHAM birds, suggesting a dissociation of reproduction from the song
      functions. Pinealectomized (PINX) birds expressed larger, more rapid increases in
      daily vocal rate and song repertoire size than did the SHAM birds during the long
      summer days. These increases gradually declined upon the extension of the long
      days and did not respond to the transfer to short days as was observed in the
      SHAM birds, suggesting that the pineal gland conveys photoperiodic information to
      the vocal control system, which in turn regulates song behavior. 

PMID- 24589992
TI  - Circular dichroism study of the interaction between mutagens and bilirubin bound
      to different binding sites of serum albumins.
AB  - Although recent investigations have shown that bilirubin not only has a negative
      role in the organism but also exhibits significant antimutagenic properties, the
      mechanisms of interactions between bilirubin and mutagens are not clear. In this
      study, interaction between bilirubin bound to different binding sites of
      mammalian serum albumins with structural analogues of the mutagens 2
      aminofluorene, 2,7-diaminofluorene and mutagen 2,4,7-trinitrofluorenone were
      investigated by circular dichroism and absorption spectroscopy. Homological human
      and bovine serum albumins were used as chiral matrices, which preferentially bind
      different conformers of bilirubin in the primary binding sites and make it
      observable by circular dichroism. These molecular systems approximated a real
      system for the study of mutagens in blood serum. Differences between the
      interaction of bilirubin bound to primary and to secondary binding sites of serum
      albumins with mutagens were shown. For bilirubin bound to secondary binding sites
      with low affinity, partial displacement and the formation of self-associates were
      observed in all studied mutagens. The associates of bilirubin bound to primary
      binding sites of serum albumins are formed with 2-aminofluorene and 2,4,7
      trinitrofluorenone. It was proposed that 2,7-diaminofluorene does not interact
      with bilirubin bound to primary sites of human and bovine serum albumins due to
      the spatial hindrance of the albumins binding domains. The spatial arrangement of
      the bilirubin bound to serum albumin along with the studied mutagens was modelled
      using ligand docking, which revealed a possibility of an arrangement of the both
      bilirubin and 2-aminofluorene and 2,4,7-trinitrofluorenone in the primary binding
      site of human serum albumin. 

PMID- 24589993
TI  - Influence of polar solvents on photovoltaic performance of Monascusred dye
      sensitized solar cell.
AB  - Dye-sensitized solar cells (DSSCs) were assembled using natural dyes extracted
      from Monascus red pigment as a sensitizer. In this work, we studied the
      adsorption characteristics for harvesting sunlight and the electrochemical
      behavior for electron transfer in Monascus red DSSC using different solvents. The
      effect of polar aprotic and protic solvents including water, ethanol, and
      dimethylsulfoxide (DMSO) used in the sensitization process was investigated for
      the improvement in conversion efficiency of a cell. As for the Monascus red dye
      sensitized electrode in DMSO solvent, the solar cell yields a short-circuit
      current density (Jsc) of 1.23mA/cm(2), a photovoltage (Voc) of 0.75V, and a fill
      factor of 0.72, corresponding to an energy conversion efficiency (eta) of 0.66%. 

PMID- 24589994
TI  - Crystal structure, Hirshfeld surfaces and DNA cleavage investigation of two
      copper(II) complexes containing polypyridine and salicylide ligands.
AB  - Two copper complexes 1 [Cu2(phen)2(salicylaldehyde)2(ClO4)2] and 2 [Cu2 (2,2'
      dipyridyl)2(salicylaldehyde)2(ClO4)2] have been synthesized and characterized by
      elemental analysis and single-crystal X-ray diffraction. These two complexes were
      display binuclear structure with Cu(II) ions in distorted octahedral environment
      but antipodal orientation of the binuclear units between them. Molecular
      Hirshfeld surfaces revealed that the crystal structures of 1 and 2 were supported
      mainly by H-H, C-H?pi, pi?pi (C-C), and C-H?O intermolecular interactions. DNA
      cleavage experiments of complexes 1 and 2 revealed that these complexes can
      intercalation with DNA. 

PMID- 24589995
TI  - The biomolecule, 2-[(2-methoxyl)sulfanyl]-4-(2-methylpropyl)-6-oxo-1,6
      dihydropyrimidine-5-carbonitrile: FT-IR, Laser-Raman spectra and DFT.
AB  - In this study, the experimental and theoretical vibrational frequencies of a
      newly synthesized potential chemotherapeutic agent namely, 2-[(2
      methoxyl)sulfanyl]-4-(2-methylpropyl)-6-oxo-1,6-dihydropyrimidine-5-carbonitrile
      have been investigated. The experimental FT-IR (4000-400cm(-1)) and Laser-Raman
      spectra (4000-100cm(-1)) of the molecule in solid phase have been recorded. The
      theoretical vibrational frequencies and optimized geometric parameters (bond
      lengths and bond angles) have been calculated by using density functional theory
      (DFT/B3LYP: Becke, 3-parameter, Lee-Yang-Parr) and M06-2X (the highly
      parametrized, empirical exchange correlation function) quantum chemical methods
      with 6-311++G(d,p) basis set by Gaussian 09W software, for the first time. The
      assignments of the vibrational frequencies have been done by potential energy
      distribution (PED) analysis by using VEDA 4 software. The theoretical optimized
      geometric parameters and vibrational frequencies have been found to be in good
      agreement with the corresponding experimental data, and with the results in the
      literature. In addition, the highest occupied molecular orbital (HOMO) energy,
      the lowest unoccupied molecular orbital (LUMO) energy and the other related
      molecular energy values of the compound have been investigated using the same
      theoretical calculations. 

PMID- 24589996
TI  - A comparative study of novel spectrophotometric methods based on isosbestic
      points; application on a pharmaceutical ternary mixture.
AB  - This work represents the application of the isosbestic points present in
      different absorption spectra. Three novel spectrophotometric methods were
      developed, the first method is the absorption subtraction method (AS) utilizing
      the isosbestic point in zero-order absorption spectra; the second method is the
      amplitude modulation method (AM) utilizing the isosbestic point in ratio spectra;
      and third method is the amplitude summation method (A-Sum) utilizing the
      isosbestic point in derivative spectra. The three methods were applied for the
      analysis of the ternary mixture of chloramphenicol (CHL), dexamethasone sodium
      phosphate (DXM) and tetryzoline hydrochloride (TZH) in eye drops in the presence
      of benzalkonium chloride as a preservative. The components at the isosbestic
      point were determined using the corresponding unified regression equation at this
      point with no need for a complementary method. The obtained results were
      statistically compared to each other and to that of the developed PLS model. The
      specificity of the developed methods was investigated by analyzing laboratory
      prepared mixtures and the combined dosage form. The methods were validated as per
      ICH guidelines where accuracy, repeatability, inter-day precision and robustness
      were found to be within the acceptable limits. The results obtained from the
      proposed methods were statistically compared with official ones where no
      significant difference was observed. 

PMID- 24589998
TI  - A review of molecular modelling of electric double layer capacitors.
AB  - Electric double-layer capacitors are a family of electrochemical energy storage
      devices that offer a number of advantages, such as high power density and long
      cyclability. In recent years, research and development of electric double-layer
      capacitor technology has been growing rapidly, in response to the increasing
      demand for energy storage devices from emerging industries, such as hybrid and
      electric vehicles, renewable energy, and smart grid management. The past few
      years have witnessed a number of significant research breakthroughs in terms of
      novel electrodes, new electrolytes, and fabrication of devices, thanks to the
      discovery of innovative materials (e.g. graphene, carbide-derived carbon, and
      templated carbon) and the availability of advanced experimental and computational
      tools. However, some experimental observations could not be clearly understood
      and interpreted due to limitations of traditional theories, some of which were
      developed more than one hundred years ago. This has led to significant research
      efforts in computational simulation and modelling, aimed at developing new
      theories, or improving the existing ones to help interpret experimental results.
      This review article provides a summary of research progress in molecular
      modelling of the physical phenomena taking place in electric double-layer
      capacitors. An introduction to electric double-layer capacitors and their
      applications, alongside a brief description of electric double layer theories, is
      presented first. Second, molecular modelling of ion behaviours of various
      electrolytes interacting with electrodes under different conditions is reviewed.
      Finally, key conclusions and outlooks are given. Simulations on comparing
      electric double-layer structure at planar and porous electrode surfaces under
      equilibrium conditions have revealed significant structural differences between
      the two electrode types, and porous electrodes have been shown to store charge
      more efficiently. Accurate electrolyte and electrode models which account for
      polarisation effects are critical for future simulations which will consider more
      complex electrode geometries, particularly for the study of dynamics of
      electrolyte transport, where the exclusion of electrode polarisation leads to
      significant artefacts. 

PMID- 24589997
TI  - Specific Inhibition of the VEGFR-3 Tyrosine Kinase by SAR131675 Reduces
      Peripheral and Tumor Associated Immunosuppressive Myeloid Cells.
AB  - Myeloid derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs)
      represent prominent components in cancer progression. We previously showed that
      inhibition of the VEGFR-3 pathway by SAR131675 leads to reduction of TAM
      infiltration and tumor growth. Here, we found that treatment with SAR131675
      prevents the accumulation of immunosuppressive blood and splenic MDSCs which
      express VEGFR-3, in 4T1 tumor bearing mice. Moreover we showed that soluble
      factors secreted by tumor cells promote MDSCs proliferation and differentiation
      into M2 polarized F4/80+ macrophages. In addition, cell sorting and
      transcriptomic analysis of tumor infiltrating myeloid cells revealed the presence
      of a heterogeneous population that could be divided into 3 subpopulations: (i)
      immature cells with a MDSC phenotype (GR1+/CD11b+/F4/80-); (ii) "immuno
      incompetent" macrophages (F4/80high/CD86neg/MHCIILow) strongly expressing M2
      markers such as Legumain, CD206 and Mgl1/2 and (iii) "immuno-competent"-M1 like
      macrophages (F4/80Low/CD86+/MHCIIHigh). SAR131675 treatment reduced MDSCs in
      lymphoid organs as well as F4/80High populations in tumors. Interestingly, in the
      tumor SAR131675 was able to increase the immunocompetent M1 like population
      (F4/80low). Altogether these results demonstrate that the specific VEGFR-3
      inhibitor SAR131675 exerts its anti tumoral activity by acting on different
      players that orchestrate immunosuppression and cancer progression in a tumoral
      context: MDSCs in peripheral lymphoid organs and TAMs infiltrating the tumor. 

PMID- 24589999
TI  - Controlled formation of cross-linked collagen fibers for neural tissue
      engineering applications.
AB  - Fibrous scaffolds engineered to direct the growth of tissues can be important in
      forming architecturally functional tissue such as aligning regenerating nerves
      with their target. Collagen is a commonly used substrate used for neuronal growth
      applications in the form of surface coatings and hydrogels. The wet spinning
      technique can create collagen fibers without the use of organic solvents and is
      typically accomplished by extruding a collagen dispersion into a coagulation
      bath. To create well-controlled and uniform collagen fibers, we developed an
      automatic wet spinning device with precise control over the spinning and fiber
      collection parameters. A fiber collection belt allowed the continuous formation
      of very soft and delicate fibers up to half a meter in length. Wet-spun collagen
      fibers were characterized by tensile and thermal behavior, diameter uniformity,
      the swelling response in phosphate buffered saline and their biocompatibility
      with dorsal root ganglion (DRG) neurons and Schwann cells. Fibers formed from
      0.75% weight by volume (w/v) collagen dispersions formed the best fibers in terms
      of tensile behavior and fiber uniformity. Fibers post-treated with the cross
      linkers glutaraldehyde and genipin exhibited increased mechanical stability and
      reduced swelling. Importantly, genipin-treated fibers were conducive to DRG
      neurons and Schwann cell survival and growth, which validated the use of this
      cross-linker for neural tissue engineering applications. 

PMID- 24590000
TI  - The peritoneum--an important factor for pathogenesis and pain generation in
      endometriosis.
AB  - Endometriosis (EM) is an oestrogen-dependent disease affecting 10-15 % of women
      during reproductive age. It is characterised by the presence of endometrial
      glands, stromal- and smooth muscle-like cells outside of the uterine cavity.
      Fifty to sixty per cent of women and teenage girls with pelvic pain suffer from
      EM. EM causes disability and compromises the quality of life in women and young
      girls significantly. Pain generation in EM is an intricate interplay of several
      factors such as the endometriotic lesions themselves and the pain-mediating
      substances, nerve fibres and cytokine-releasing immune cells such as macrophages.
      These interactions seem to induce a neurogenic inflammatory process. Recently
      published data demonstrated an increased peptidergic and decreased noradrenergic
      nerve fibre density in peritoneal lesions. These data could be substantiated by
      in vitro analyses demonstrating that the peritoneal fluids of patients suffering
      from EM induced an enhanced sprouting of sensory neurites from chicken dorsal
      root ganglia and decreased neurite outgrowth from sympathetic ganglia. These
      findings might be directly involved in the perpetuation of inflammation and pain.
      Furthermore, the evidence of EM-associated smooth muscle-like cells seems another
      important factor in pain generation. The peritoneal endometriotic lesion leads to
      reactions in the surrounding tissue and, therefore, is larger than generally
      believed. The identification of EM-associated nerve fibres and smooth muscle-like
      cells fuel discussions on the mechanisms of pain generation in EM, and may
      present new targets for innovative treatments.

PMID- 24590002
TI  - Suicide risk among soldiers: early findings from Army Study to Assess Risk and
      Resilience in Servicemembers (Army STARRS).

PMID- 24590003
TI  - Successful ablation of a bioresorbable polymeric vascular scaffold by rotational
      atherectomy.

PMID- 24590001
TI  - Amphiphysin 2 (BIN1) in physiology and diseases.
AB  - Amphiphysin 2, also named bridging integrator-1 (BIN1) or SH3P9, has been
      recently implicated in rare and common diseases affecting different tissues and
      physiological functions. BIN1 downregulation is linked to cancer progression and
      also correlates with ventricular cardiomyopathy and arrhythmia preceding heart
      failure. Increased BIN1 expression is linked to increased susceptibility for late
      onset Alzheimer's disease. In addition, altered splicing may account for the
      muscle component of myotonic dystrophies, while recessive germinal mutations
      cause centronuclear myopathy. Despite undoubtedly underlining the relevance of
      BIN1 in human diseases, the molecular and cellular bases leading to such
      different diseases are unclear at present. BIN1 is a key regulator of endocytosis
      and membrane recycling, cytoskeleton regulation, DNA repair, cell cycle
      progression, and apoptosis. In light of the recent findings on the molecular,
      cellular, and physiological roles of BIN1, we discuss potential pathological
      mechanisms and highlight common disease pathways and also tissue-specific
      regulation. Next challenges will be to validate BIN1 both as a prognostic marker
      for the related diseases and as a potential therapeutic target. 

PMID- 24590004
TI  - Rice bran and raspberry seed oil-based nanocarriers with self-antioxidative
      properties as safe photoprotective formulations.
AB  - The aim of this research was to develop advanced lipid nanocarriers based on
      renewable vegetable resources (rice bran oil and raspberry seed oil) that possess
      self-antioxidative properties, having advantages in terms of minimal side effects
      and exhibiting the ability to simultaneously co-encapsulate and co-release two
      active compounds. The focus has been oriented towards developing safe cosmetic
      formulations with broad-spectrum photoprotection based on these new lipid
      nanocarriers that contain large amounts of vegetable oils and low concentrations
      of synthetic UVA and UVB filters (butyl-methoxydibenzoylmethane - BMDBM and
      octocrylene - OCT). The lipid nanocarriers have a spherical shape and show good
      physical stability, with a zeta potential in the range of -25.5 to -32.4 mV. Both
      vegetable oils play a key role in the preparation of efficient nanocarriers,
      leading to a less ordered arrangement of the lipid core that offers many spaces
      for the entrapment of large amounts of BMDBM (79%) and OCT (90%), as wells as
      improved antioxidant activity and UV absorption properties, particularly for the
      lipid nanocarriers prepared from rice bran oil. By formulating the lipid
      nanocarriers into creams containing only 3.5% of the UV filters and 10.5% of the
      vegetable oils, the resulting sunscreens exhibited improved photoprotection,
      reflecting up to 91% and 93% of UVA and UVB rays, respectively. A new direction
      of research achieved by this study is the multiple release strategy of both UV
      filters from the same lipid nanocarrier. After 24 hours, a slow release of BMDBM
      (less than 4%) and OCT (17.5%) was obtained through a Fick diffusion process.
      This study demonstrates a significant advance in the areas of both nanotechnology
      and cosmetics, developing safer cosmetic formulations that possess broad
      antioxidant, photoprotective and co-release effectiveness due to the existence of
      a high content of nanostructured vegetable oils combined with a low amount of
      synthetic UV filters in the same carrier system. 

PMID- 24590005
TI  - Comparison of landing biomechanics between male and female dancers and athletes,
      part 1: Influence of sex on risk of anterior cruciate ligament injury.
AB  - BACKGROUND: The incidence of anterior cruciate ligament (ACL) injuries among
      dancers is much lower than among team sport athletes, and no clear disparity
      between sexes has been reported in the dance population. Although numerous
      studies have observed differences in landing biomechanics of the lower extremity
      between male and female team sport athletes, there is currently little research
      examining the landing biomechanics of male and female dancers and none comparing
      athletes to dancers. Comparing the landing biomechanics within these populations
      may help explain the lower overall ACL injury rates and lack of sex disparity.
      HYPOTHESIS: The purpose was to compare the effects of sex and group (dancer vs
      team sport athlete) on single-legged drop-landing biomechanics. The primary
      hypothesis was that female dancers would perform a drop-landing task without
      demonstrating typical sex-related risk factors associated with ACL injuries. A
      secondary hypothesis was that female team sport athletes would display typical
      ACL risk factors during the same task. STUDY DESIGN: Controlled laboratory study.
      METHODS: Kinematics and kinetics were recorded as 40 elite modern and ballet
      dancers (20 men and 20 women) and 40 team sport athletes (20 men and 20 women)
      performed single-legged drop landings from a 30-cm platform. Joint kinematics and
      kinetics were compared between groups and sexes with a group-by-sex multivariate
      analysis of variance (MANOVA) followed by pairwise t tests. RESULTS: Dancers of
      both sexes and male team sport athletes landed similarly in terms of frontal
      plane knee alignment, whereas female team sport athletes landed with a
      significantly greater peak knee valgus (P = .007). Female dancers were found to
      have a lower hip adduction torque than those of the other 3 groups (P = .003).
      Dancers (male and female) exhibited a lower trunk side flexion (P = .002) and
      lower trunk forward flexion (P = .032) compared with team sport athletes.
      CONCLUSION: In executing a 30-cm drop landing, female team sport athletes
      displayed a greater knee valgus than did the other 3 groups. Dancers exhibited
      better trunk stability than did athletes. CLINICAL RELEVANCE: These biomechanical
      findings may provide insight into the cause of the epidemiological differences in
      ACL injuries between dancers and athletes and the lack of a sex disparity within
      dancers.

PMID- 24590006
TI  - Increased slope of the lateral tibial plateau subchondral bone is associated with
      greater risk of noncontact ACL injury in females but not in males: a prospective
      cohort study with a nested, matched case-control analysis.
AB  - BACKGROUND: There is an emerging consensus that increased posterior-inferior
      directed slope of the subchondral bone portion of the tibial plateau is
      associated with increased risk of suffering an anterior cruciate ligament (ACL)
      injury; however, most of what is known about this relationship has come from
      unmatched case-control studies. These observations need to be confirmed in more
      rigorously designed investigations. HYPOTHESIS: Increased posterior-inferior
      directed slope of the medial and lateral tibial plateaus are associated with
      increased risk of suffering a noncontact ACL injury. STUDY DESIGN: Case-control
      study; Level of evidence, 3. METHODS: In sum, 176 athletes competing in organized
      sports at the college and high school levels participated in the study: 88
      suffering their first noncontact ACL injury and 88 matched controls. Magnetic
      resonance images were acquired, and geometry of the subchondral bone portion of
      the tibial plateau was characterized on each athlete bilaterally by measuring the
      medial and lateral tibial plateau slopes, coronal tibial slope, and the depth of
      the medial tibial plateau. Comparisons between knees of the same person were made
      with paired t tests, and associations with injury risk were assessed by
      conditional logistic regression analysis of ACL-injured and control participants.
      RESULTS: Controls exhibited side-to-side symmetry of subchondral bone geometry,
      while the ACL-injured athletes did not, suggesting that the ACL injury may have
      changed the subchondral bone geometry. Therefore, the uninjured knees of the ACL
      injured athletes and the corresponding limbs of their matched controls were used
      to assess associations with injury risk. Analyses of males and females as a
      combined group and females as a separate group showed a significant association
      between ACL injury risk and increased posterior-inferior directed slope of the
      lateral tibial plateau slope. This relationship was not apparent when males were
      analyzed as a group. Multivariate analyses indicated that these results were
      independent of the medial tibial plateau slope, coronal tibial slope, and depth
      of the medial tibial plateau, which were not associated with ACL injury.
      CONCLUSION: There is a 21.7% increased risk of noncontact ACL injury with each
      degree increase of the lateral tibial plateau slope among females but not among
      males. The medial tibial plateau slope, coronal tibial slope, and depth of the
      medial tibial plateau were not associated with risk of injury for females or
      males.

PMID- 24590008
TI  - The reactivity game: theoretical predictions for heavy atom tunneling in
      adamantyl and related carbenes.
AB  - The possibility of carbon atom tunneling at cryogenic temperatures for carbene
      based ring expansion of adamantane analogues calls for a delicate balance of
      reactivity to experimentally detect the transpiring reaction. An overly reactive
      carbene will precipitously decay; an excessively stable carbene will not tunnel.
      Nevertheless, the factors that affect the quantum-mechanical tunneling (QMT)
      reactivity - mass, barrier height and width - are strikingly different from the
      classical "over the barrier" thermal mechanism. Herein, comparisons with
      experimental values and predictions on measurable rate constants for novel
      carbene systems are presented by way of small curvature tunneling (SCT)
      computations. Adamantane, noradamantane and bisnoradamantane have a significantly
      different C-C bond strain and reactivity, which can be modulated by tinkering
      with the carbene substituent atom (H, Cl or F) to obtain an observable lifetime
      of the reactant. The influence of barrier heights and widths, kinetic isotope
      effects (KIEs), the detection of the tunneling-determining atoms (TDA) and the
      comparisons with hydrogen-based reactions are discussed with the objective of
      finding the physical limits for QMT. 

PMID- 24590007
TI  - Endometrial cancer after endometrial ablation vs medical management of abnormal
      uterine bleeding.
AB  - STUDY OBJECTIVE: To investigate whether endometrial ablation is associated with
      increased risk or delayed diagnosis of endometrial cancer compared with medical
      management of abnormal uterine bleeding. DESIGN: Multi-centered retrospective
      cohort study (Canadian Task Force classification II-2). SETTING: The study was
      performed using data from The Health Improvement Network, a representative
      population-based cohort of patients in 495 outpatient general practitioner
      practices in the United Kingdom. PATIENTS: Women aged >25 years with abnormal
      uterine bleeding diagnosed between June 1994 and September 2010. INTERVENTIONS:
      Endometrial ablation, medical management, or both. MEASUREMENTS AND MAIN RESULTS:
      A total of 234 721 women met study inclusion and exclusion criteria, 4776 of whom
      underwent endometrial ablation and the remaining 229 945 received medical
      management. Cox models compared endometrial cancer rates between ablation and
      medical management groups using hazard ratios. To investigate a possible
      diagnostic delay, the median time from bleeding diagnosis to endometrial cancer
      diagnosis in women in whom endometrial cancer developed was compared using the
      Mann-Whitney U test. All statistical tests were 2-tailed, with alpha = .05.
      During a median observation period of 4.07 years (interquartile range [IQR], 1.88
      7.17), endometrial cancer developed in 3 women in the ablation group and 601
      women in the medical management group (ablation hazard ratio, 0.45; 95%
      confidence interval, 0.15-1.40; p = .17). Median time to diagnosis was 237 in the
      ablation group, and 299 days in the medical management group (ablation IQR, 155
      1350; medical management IQR, 144-1133.5; p = .99). Adjusted and sensitivity
      analyses did not change the results. CONCLUSIONS: No difference was observed in
      endometrial cancer rates, and there was no delay in diagnosis when comparing
      endometrial ablation vs medical management. Further studies are needed to
      investigate the effect of previous ablation exposure on histology or cancer stage
      at manifestation of endometrial cancer.

PMID- 24590009
TI  - What do healthcare providers know about nutrition support? A survey of the
      knowledge, attitudes, and practice of pharmacists and doctors toward nutrition
      support in Malaysia.
AB  - BACKGROUND AND AIMS: Malnutrition is one of the health problems that can be
      prevented by appropriate nutrition care provided by healthcare providers.
      However, this practice is still lacking possibly because of the providers'
      inadequate knowledge. The aim of this study was to evaluate the self-reported
      knowledge, attitudes, and practices of pharmacists and doctors toward nutrition
      support in a tertiary care hospital setting. METHODS: A validated questionnaire
      was distributed to all the doctors and pharmacists working in a tertiary hospital
      in Penang, Malaysia. Seven individuals including academics, general surgeons, and
      pharmacists performed the face and content validity. The questionnaire was
      piloted using 24 healthcare providers at a different hospital. RESULT: Of 400
      surveyed, 158 doctors and 72 pharmacists from various grades completed the
      questionnaire. More doctors (31.6%) than pharmacists (15.3%) reported adequate
      knowledge to perform patients' nutrition screening. However, in the knowledge
      assessment, pharmacists had a higher mean score (6.07 +/- 1.77) than the doctors
      did (4.59 +/- 1.87; P < .001), and most (70.4%) of them were grouped in the
      "average" score range. In addition, both pharmacists and doctors have ambivalent
      attitudes toward nutrition support. Only 31.3% stated that they perform nutrition
      screening on admission, and half of them performed nutrition assessment during
      hospitalization. CONCLUSION: Inappropriate nutrition care might be due to the
      lack of guidelines and insufficient knowledge among doctors and pharmacists.
      Special nutrition training and education for both pharmacists and doctors should
      be established.

PMID- 24590010
TI  - Electron paramagnetic resonance study of ZnO varistor material.
AB  - Matsuoka-type zinc oxide (ZnO) varistor material was synthesized using a
      conventional solid-state reaction method. X-band electron paramagnetic resonance
      (EPR) data revealed that Mn ions substitute in the ZnO lattice with a 2+
      paramagnetic state. Co ions with either 3+ or 2+ oxidation states are only
      detectable at cryogenic temperatures. A Cr(3+) EPR signal was strongly suppressed
      or masked by a Mn(2+) signal. Photoluminescence and electrical results indicated
      that the varistor sample has fewer intrinsic defects and much higher resistivity
      as compared to undoped and metal-ion doped ZnO. 

PMID- 24590011
TI  - Extreme learning machine for ranking: generalization analysis and applications.
AB  - The extreme learning machine (ELM) has attracted increasing attention recently
      with its successful applications in classification and regression. In this paper,
      we investigate the generalization performance of ELM-based ranking. A new
      regularized ranking algorithm is proposed based on the combinations of activation
      functions in ELM. The generalization analysis is established for the ELM-based
      ranking (ELMRank) in terms of the covering numbers of hypothesis space. Empirical
      results on the benchmark datasets show the competitive performance of the ELMRank
      over the state-of-the-art ranking methods. 

PMID- 24590012
TI  - Radiation risk from lung cancer screening: glowing in the dark?

PMID- 24590013
TI  - Nodule volume measurement: pushing the pendulum.

PMID- 24590014
TI  - A new paradigm: approaching racism as a method of disease prevention.

PMID- 24590015
TI  - Illusions and delusions of cut, pasted, and cloned notes: ephemeral reality and
      pixel prevarications.

PMID- 24590017
TI  - Point: should ultrasonographic endoscopy be the preferred modality for staging of
      lung cancer? Yes.

PMID- 24590018
TI  - Counterpoint: should ultrasonographic endoscopy be the preferred modality for
      staging of lung cancer? No.

PMID- 24590019
TI  - Rebuttal from drs Wahidi and Ernst.

PMID- 24590020
TI  - Rebuttal from drs Farjah and Wood.

PMID- 24590022
TI  - Radiation risks in lung cancer screening programs: a comparison with nuclear
      industry workers and atomic bomb survivors.
AB  - The National Lung Cancer Screening Trial (NLST) demonstrated that screening with
      low-dose CT (LDCT) scan reduced lung cancer and overall mortality by 20% and 7%,
      respectively. The LDCT scanning involves an approximate 2-mSv dose, whereas full
      chest CT scanning, the major diagnostic study used to follow up nodules, may
      involve a dose of 8 mSv. Radiation associated with CT scanning and other
      diagnostic studies to follow up nodules may present an independent risk of lung
      cancer. On the basis of the NLST, we estimated the incidence and prevalence of
      nodules detected in screening programs. We followed the Fleischner guidelines for
      follow-up of nodules to assess cumulative radiation exposure over 20- and 30-year
      periods. We then evaluated nuclear worker cohort studies and atomic bomb survivor
      studies to assess the risk of lung cancer from radiation associated with long
      term lung cancer screening programs. The findings indicate that a 55-year-old
      lung screening participant may experience a cumulative radiation exposure of up
      to 280 mSv over a 20-year period and 420 mSv over 30 years. These exposures
      exceed those of nuclear workers and atomic bomb survivors. This assessment
      suggests that long-term (20-30 years) LDCT screening programs are associated with
      nontrivial cumulative radiation doses. Current lung cancer screening protocols,
      if conducted over 20- to 30-year periods, can independently increase the risk of
      lung cancer beyond cigarette smoking as a result of cumulative radiation
      exposure. Radiation exposures from LDCT screening and follow-up diagnostic
      procedures exceed lifetime radiation exposures among nuclear power workers and
      atomic bomb survivors. 

PMID- 24590023
TI  - Challenges in deactivating a total artificial heart for a patient with capacity.
AB  - The use of mechanical circulatory support (MCS) devices has increased sixfold
      since 2006. Although there is an established legal and ethical consensus that
      patients have the right to withdraw and withhold life-sustaining interventions
      when burdens exceed benefits, this consensus arose prior to the widespread use of
      MCS technology and is not uniformly accepted in these cases. There are unique
      ethical and clinical considerations regarding MCS deactivation. Our center
      recently encountered the challenge of an awake and functionally improving patient
      with a total artificial heart (TAH) who requested its deactivation. We present a
      narrative description of this case with discussion of the following questions:
      (1) Is it ethically permissible to deactivate this particular device, the TAH?
      (2) Are there any particular factors in this case that are ethical
      contraindications to proceeding with deactivation? (3) What are the specific
      processes necessary to ensure a compassionate and respectful deactivation? (4)
      What proactive practices could have been implemented to lessen the intensity of
      this case's challenges? We close with a list of recommendations for managing
      similar cases. 

PMID- 24590021
TI  - A roadmap to promote clinical and translational research in rheumatoid arthritis
      associated interstitial lung disease.
AB  - Rheumatoid arthritis (RA) is a systemic inflammatory disorder affecting
      approximately 1.3 million adults in the United States. Approximately 10% of these
      individuals with RA have clinically evident interstitial lung disease (RA-ILD),
      and an additional one-third demonstrate subclinical ILD on chest CT scan. The
      risk of death for individuals with RA-ILD is three times higher than for patients
      with RA without ILD, with a median survival after ILD diagnosis of only 2.6
      years. Despite the high prevalence and mortality of RA-ILD, little is known about
      its molecular features and its natural history. At present, we lack a standard
      validated approach to the definition, diagnosis, risk stratification, and
      management of RA-ILD. In this perspective, we discuss the importance of clinical
      and translational research and how ongoing research efforts can address important
      gaps in our knowledge over the next few years. Furthermore, recommendations are
      made to design multicenter collaborative studies that will expedite the
      development of clinical trials designed to decrease the significant morbidity and
      mortality associated with RA-ILD. 

PMID- 24590024
TI  - Copy, paste, and cloned notes in electronic health records: prevalence, benefits,
      risks, and best practice recommendations.
AB  - The modern medical record is not only used by providers to record nuances of
      patient care, but also is a document that must withstand the scrutiny of
      insurance payers and legal review. Medical documentation has evolved with the
      rapid growth in the use of electronic health records (EHRs). The medical software
      industry has created new tools and more efficient ways to document patient care
      encounters and record results of diagnostic testing. While these techniques have
      resulted in efficiencies and improvements in patient care and provider
      documentation, they have also created a host of new problems, including
      authorship attribution, data integrity, and regulatory concerns over the accuracy
      and medical necessity of billed services. Policies to guide provider
      documentation in EHRs have been developed by institutions and payers with the
      goal of reducing patient care risks as well as preventing fraud and abuse. In
      this article, we describe the major content-importing technologies that are
      commonly used in EHR documentation as well as the benefits and risks associated
      with their use. We have also reviewed a number of institutional policies and
      offer some best practice recommendations. 

PMID- 24590025
TI  - A case of pulmonary hemorrhage due to drug-induced pneumonitis secondary to
      ticagrelor therapy.
AB  - We report a case of significant pulmonary hemorrhage developing shortly after
      commencing ticagrelor and aspirin therapy and requiring coronary artery bypass
      grafting to safely cease the antiplatelet therapy. Lung biopsy findings were
      consistent with drug-induced lung injury. Clinicians should be aware of this
      significant adverse event with this drug class. 

PMID- 24590026
TI  - A 55-year-old woman with pulmonary hypertension, worsening dyspnea, and chest
      pain. Diagnosis: Extrinsic compression of the left main coronary artery by the
      pulmonary artery.

PMID- 24590027
TI  - Innovative designs for the smart ICU: Part 2: The ICU.
AB  - Successfully designing a new ICU requires clarity of vision and purpose and the
      recognition that the patient room is the core of the ICU experience for patients,
      staff, and visitors. The ICU can be conceptualized into three components: the
      patient room, central areas, and universal support services. Each patient room
      should be designed for single patient use and be similarly configured and
      equipped. The design of the room should focus upon functionality, ease of use,
      healing, safety, infection control, communications, and connectivity. All aspects
      of the room, including its infrastructure; zones for work, care, and visiting;
      environment, medical devices, and approaches to privacy; logistics; and waste
      management, are important elements in the design process. Since most medical
      devices used at the ICU bedside are really sophisticated computers, the ICU needs
      to be capable of supporting the full scope of medical informatics. The patient
      rooms, the central ICU areas (central stations, corridors, supply rooms,
      pharmacy, laboratory, staff lounge, visitor waiting room, on-call suite,
      conference rooms, and offices), and the universal support services (infection
      prevention, finishings and flooring, staff communications, signage and
      wayfinding, security, and fire and safety) work best when fully interwoven. This
      coordination helps establish efficient and safe patient throughput and care and
      fosters physical and social cohesiveness within the ICU. A balanced approach to
      centralized and decentralized monitoring and logistics also offers great
      flexibility. Synchronization of the universal support services in the ICU with
      the hospital's existing systems maintains unity of purpose and continuity across
      the enterprise and avoids unnecessary duplication of efforts. 

PMID- 24590032
TI  - Isolated reduction of the FEV3/FVC ratio as an indicator of mild airflow
      obstruction.

PMID- 24590033
TI  - Response.

PMID- 24590034
TI  - Pneumocystis pneumonia following rituximab.

PMID- 24590035
TI  - Response.

PMID- 24590036
TI  - Recovery of consciousness after head injury.

PMID- 24590037
TI  - Response.

PMID- 24590038
TI  - Psychiatric morbidity in patients with lung cancer.

PMID- 24590039
TI  - Response.

PMID- 24590040
TI  - Fever control and sepsis mortality.

PMID- 24590041
TI  - Response.

PMID- 24590042
TI  - Ciliated cultures from patients with primary ciliary dyskinesia produce nitric
      oxide in response to Haemophilus influenzae infection and proinflammatory
      cytokines.

PMID- 24590043
TI  - Response.

PMID- 24590044
TI  - A woman in her 60s with septic shock, abdominal pain, and a positive urinalysis.
      Next steps: Urgent source control with a percutaneous nephrostomy tube.

PMID- 24590045
TI  - Supplementation of influenza split vaccines with conserved M2 ectodomains
      overcomes strain specificity and provides long-term cross protection.
AB  - Current influenza vaccines do not provide good protection against antigenically
      different influenza A viruses. As an approach to overcome strain specificity of
      protection, this study demonstrates significantly improved long-term cross
      protection by supplementing split vaccines with a conserved molecular target, a
      repeat of the influenza M2 ectodomain (M2e) expressed on virus-like particles
      (M2e5x VLPs) in a membrane-anchored form. Intramuscular immunization with H1N1
      split vaccine (A/California/07/2009) supplemented with M2e5x VLPs induced M2e
      specific humoral and cellular immune responses, and shaped the host responses to
      the vaccine in the direction of T-helper type 1 responses inducing dominant IgG2a
      isotype antibodies as well as interferon-gamma (IFN-gamma) producing cells in
      systemic and mucosal sites. Upon lethal challenge, M2e5x VLP-supplemented
      vaccination lowered lung viral loads and induced long-term cross protection
      against H3N2 or H5N1 subtype influenza viruses over 12 months. M2e antibodies,
      CD4 T cells, and CD8 T cells were found to contribute to improving heterosubtypic
      cross protection. In addition, improved cross protection by supplemented
      vaccination with M2e5x VLPs was mediated via Fc receptors. The results support
      evidence that supplementation with M2e5x VLPs is a promising approach for
      overcoming the limitation of strain-specific protection by current influenza
      vaccination. 

PMID- 24590046
TI  - Bacterial delivery of Staphylococcus aureus alpha-hemolysin causes regression and
      necrosis in murine tumors.
AB  - Bacterial therapies, designed to manufacture therapeutic proteins directly within
      tumors, could eliminate cancers that are resistant to other therapies. To be
      effective, a payload protein must be secreted, diffuse through tissue, and
      efficiently kill cancer cells. To date, these properties have not been shown for
      a single protein. The gene for Staphylococcus aureus alpha-hemolysin (SAH), a
      pore-forming protein, was cloned into Escherichia coli. These bacteria were
      injected into tumor-bearing mice and volume was measured over time. The location
      of SAH relative to necrosis and bacterial colonies was determined by
      immunohistochemistry. In culture, SAH was released and killed 93% of cancer cells
      in 24 hours. Injection of SAH-producing bacteria reduced viable tissue to 9% of
      the original tumor volume. By inducing cell death, SAH moved the boundary of
      necrosis toward the tumor edge. SAH diffused 6.8 +/- 0.3 um into tissue, which
      increased the volume of affected tissue from 48.6 to 3,120 um(3). A mathematical
      model of molecular transport predicted that SAH efficacy is primarily dependent
      on colony size and the rate of protein production. As a payload protein, SAH will
      enable effective bacterial therapy because of its ability to diffuse in tissue,
      kill cells, and expand tumor necrosis. 

PMID- 24590047
TI  - The strength of the T cell response against a surrogate tumor antigen induced by
      oncolytic VSV therapy does not correlate with tumor control.
AB  - Cancer therapy using oncolytic viruses has gained interest in the last decade.
      Vesicular stomatitis virus is an attractive candidate for this alternative
      treatment approach. The importance of the immune response against tumor antigens
      in virotherapy efficacy is now well recognized, however, its relative
      contribution versus the intrinsic oncolytic capacity of viruses has been
      difficult to evaluate. To start addressing this question, we compared
      glycoprotein and matrix mutants of vesicular stomatitis virus (VSV), showing
      different oncolytic potentials for B16/B16gp33 melanoma tumor cells in vitro,
      with the wild-type virus in their ability to induce tumor-specific CD8(+) T cell
      responses and control tumor progression in vivo. Despite the fact that wild-type
      and G mutants induced a stronger gp33-specific immune response compared to the
      MM51R mutant, all VSV strains showed a similar capacity to slow down tumor
      progression. The effectiveness of the matrix mutant treatment proved to be CD8(+)
      dependent and directed against tumor antigens other than gp33 since adoptive
      transfer of isolated CD8(+) T lymphocytes from treated B16gp33-bearing mice
      resulted in significant protection of naive mice against challenge with the
      parental tumor. Remarkably, the VSV matrix mutant induced the upregulation of
      major histocompatibility class-I antigen at the tumor cell surface thus favoring
      recognition by CD8(+) T cells. These results demonstrate that VSV mutants induce
      an antitumor immune response using several mechanisms. A better understanding of
      these mechanisms will prove useful for the rational design of viruses with
      improved therapeutic efficacy. 

PMID- 24590049
TI  - Assessment of ecological and human health risks of heavy metal contamination in
      agriculture soils disturbed by pipeline construction.
AB  - The construction of large-scale infrastructures such as nature gas/oil pipelines
      involves extensive disturbance to regional ecosystems. Few studies have
      documented the soil degradation and heavy metal contamination caused by pipeline
      construction. In this study, chromium (Cr), cadmium (Cd), copper (Cu), nickel
      (Ni), lead (Pb) and zinc (Zn) levels were evaluated using Index of Geo
      accumulation (Igeo) and Potential Ecological Risk Index (RI) values, and human
      health risk assessments were used to elucidate the level and spatial variation of
      heavy metal pollution risks. The results showed that the impact zone of pipeline
      installation on soil heavy metal contamination was restricted to pipeline right
      of-way (RoW), which had higher Igeo of Cd, Cu, Ni and Pb than that of 20 m and 50
      m. RI showed a declining tendency in different zones as follows: trench > working
      zone > piling area > 20 m > 50 m. Pipeline RoW resulted in higher human health
      risks than that of 20 m and 50 m, and children were more susceptible to non
      carcinogenic hazard risk. Cluster analysis showed that Cu, Ni, Pb and Cd had
      similar sources, drawing attention to the anthropogenic activity. The findings in
      this study should help better understand the type, degree, scope and sources of
      heavy metal pollution from pipeline construction to reduce pollutant emissions,
      and are helpful in providing a scientific basis for future risk management. 

PMID- 24590048
TI  - Predictors of suicide and accident death in the Army Study to Assess Risk and
      Resilience in Servicemembers (Army STARRS): results from the Army Study to Assess
      Risk and Resilience in Servicemembers (Army STARRS).
AB  - IMPORTANCE: The Army Study to Assess Risk and Resilience in Servicemembers (Army
      STARRS) is a multicomponent study designed to generate actionable recommendations
      to reduce Army suicides and increase knowledge of risk and resilience factors for
      suicidality. OBJECTIVES: To present data on prevalence, trends, and basic
      sociodemographic and Army experience correlates of suicides and accident deaths
      among active duty Regular Army soldiers between January 1, 2004, and December 31,
      2009, and thereby establish a foundation for future Army STARRS investigations.
      DESIGN, SETTING, AND PARTICIPANTS: Analysis of trends and predictors of suicide
      and accident deaths using Army and Department of Defense administrative data
      systems. Participants were all members of the US Regular Army serving at any time
      between 2004 and 2009. MAIN OUTCOMES AND MEASURES: Death by suicide or accident
      during active Army service. RESULTS: The suicide rate rose between 2004 and 2009
      among never deployed and currently and previously deployed Regular Army soldiers.
      The accident death rate fell sharply among currently deployed soldiers, remained
      constant among the previously deployed, and trended upward among the never
      deployed. Increased suicide risk was associated with being a man (or a woman
      during deployment), white race/ethnicity, junior enlisted rank, recent demotion,
      and current or previous deployment. Sociodemographic and Army experience
      predictors were generally similar for suicides and accident deaths. Time trends
      in these predictors and in the Army's increased use of accession waivers (which
      relaxed some qualifications for new soldiers) do not explain the rise in Army
      suicides. CONCLUSIONS AND RELEVANCE: Predictors of Army suicides were largely
      similar to those reported elsewhere for civilians, although some predictors
      distinct to Army service emerged that deserve more in-depth analysis. The
      existence of a time trend in suicide risk among never-deployed soldiers argues
      indirectly against the view that exposure to combat-related trauma is the
      exclusive cause of the increase in Army suicides.

PMID- 24590050
TI  - Level and contamination assessment of environmentally sensitive elements in
      smaller than 100 MUm street dust particles from Xining, China.
AB  - Concentrations of the environmentally sensitive elements (ESEs) As, Co, Cu, Mn,
      Ni, Pb, V and Zn in smaller than 100 MUm street dust particles from Xining were
      measured using X-ray fluorescence spectrometry and their contamination levels
      were assessed based on enrichment factor (EF), geoaccumulation index (Igeo) and
      pollution load index (PLI). The concentrations of As, Co, Cu, Mn, Ni, Pb, V and
      Zn in smaller than 100 MUm street dust particles from Xining are 0.1-0.8, 2.7
      10.9, 0.7-5.2, 0.3-1.1, 0.6-2.5, 1.2-11.1, 0.7-1.3 and 0.4-2.9 times the
      background values of Qinghai soil, respectively. The calculated EF and Igeo
      values reveal the order Co > Pb > Cu > Zn > V > Ni > Mn > As. The EF and Igeo
      values of Co, Cu, Pb and Zn are higher indicating that there is considerable
      pollution by these elements in smaller than 100 MUm street dust particles,
      especially for Co. The EF and Igeo of Mn, Ni and V are lower and the assessment
      results indicate an absence of distinct Mn, Ni and V pollution in the studied
      samples. The mean value of PLIsite is 1.14, indicating a slightly pollution in
      the whole city of Xining. The order of PLIarea for the five tested districts is
      Center District (CD) > East District (ED) > West District (WD) > North District
      (ND) > South District (SD), showing that ESEs pollution in the South District is
      the lightest while it is the highest in the Central District. 

PMID- 24590051
TI  - Identifying regional key eco-space to maintain ecological security using GIS.
AB  - Ecological security and environmental sustainability are the foundations of
      sustainable development. With the acceleration of urbanization, increasing human
      activities have promoted greater impacts on the eco-spaces that maintain
      ecological security. Regional key eco-space has become the primary need to
      maintain environmental sustainability and can offer society with continued
      ecosystem services. In this paper, considering the security of water resources,
      biodiversity conservation, disaster avoidance and protection and natural
      recreation, an integrated index of eco-space importance was established and a
      method for identifying key eco-space was created using GIS, with Lanzhou City,
      China as a case study. The results show that the area of core eco-space in the
      Lanzhou City is approximately 50,908.7 hm(2), accounting for 40% of the region's
      total area. These areas mainly consist of geological hazard protection zones and
      the core zones of regional river systems, wetlands, nature reserves, forest parks
      and scenic spots. The results of this study provide some guidance for the
      management of ecological security, ecological restoration and environmental
      sustainability.

PMID- 24590052
TI  - Continuous kynurenine administration during the prenatal period, but not during
      adolescence, causes learning and memory deficits in adult rats.
AB  - RATIONALE: Cognitive dysfunctions, including deficits in hippocampus-mediated
      learning and memory, are core features of the psychopathology of schizophrenia
      (SZ). Increased levels of kynurenic acid (KYNA), an astrocyte-derived tryptophan
      metabolite and antagonist of alpha7 nicotinic acetylcholine and N-methyl-D
      aspartate receptors, have been implicated in these cognitive impairments.
      OBJECTIVES: Following recent suggestive evidence, the present study was designed
      to narrow the critical time period for KYNA elevation to induce subsequent
      cognitive deficits. METHODS: KYNA levels were experimentally increased in rats
      (1) prenatally (embryonic day (ED) 15 to ED 22) or (2) during adolescence
      (postnatal day (PD) 42 to PD 49). The KYNA precursor kynurenine was added daily
      to wet mash fed to (1) dams (100 mg/day; control: ECon; kynurenine-treated: EKyn)
      or (2) adolescent rats (300 mg/kg/day; control: AdCon; kynurenine-treated:
      AdKyn). Upon termination of the treatment, all animals were fed normal chow until
      biochemical analysis and behavioral testing in adulthood. RESULTS: On the last
      day of continuous kynurenine treatment, forebrain KYNA levels were significantly
      elevated (EKyn +472 %; AdKyn +470 %). KYNA levels remained increased in the
      hippocampus of adult EKyn animals (+54 %), but were unchanged in adult AdKyn
      rats. Prenatal, but not adolescent, kynurenine treatment caused significant
      impairments in two hippocampus-mediated behavioral tasks, passive avoidance and
      Morris water maze. CONCLUSIONS: Collectively, these studies provide evidence that
      a continuous increase in brain KYNA levels during the late prenatal period, but
      not during adolescence, induces hippocampus-related cognitive dysfunctions later
      in life. Such increases may play a significant role in illnesses with known
      hippocampal pathophysiology, including SZ.

PMID- 24590053
TI  - Effects of blue light and caffeine on mood.
AB  - RATIONALE: Both short wavelength (blue) light and caffeine have been studied for
      their mood enhancing effects on humans. The ability of blue light to increase
      alertness, mood and cognitive function via non-image forming neuropathways has
      been suggested as a non-pharmacological countermeasure for depression across a
      range of occupational settings. OBJECTIVES: This experimental study compared blue
      light and caffeine and aimed to test the effects of blue light/placebo (BLU),
      white light/240-mg caffeine (CAF), blue light/240-mg caffeine (BCAF) and white
      light/placebo (PLA), on mood. METHODS: A randomised, controlled, crossover design
      study was used, in a convenience population of 20 healthy volunteers. The
      participants rated their mood on the Swedish Core Affect Scales (SCAS) prior to
      and after each experimental condition to assess the dimensions of valence and
      activation. RESULTS: There was a significant main effect of light (p = 0.009),
      and the combination of blue light and caffeine had clear positive effects on core
      effects (ES, ranging from 0.41 to 1.20) and global mood (ES, 0.61 +/- 0.53).
      CONCLUSIONS: The benefits of the combination of blue light and caffeine should be
      further investigated across a range of applications due to the observed effects
      on the dimensions of arousal, valence and pleasant activation.

PMID- 24590055
TI  - Light to investigate (read) and operate (write) molecular devices and machines.
AB  - The development of multicomponent (supramolecular) systems that can perform
      predetermined functions under external control - i.e., molecular devices - is a
      challenging task in chemistry and a fascinating objective in the frame of a
      bottom-up approach to nanostructures. In this context light signals can be
      conveniently used both for supplying energy to the system and for probing its
      states and transformations. The aim of this tutorial review is to recall a few
      basic aspects of light-induced processes that can be used to "write" and "read"
      onto molecular and supramolecular systems. These principles are illustrated
      through some examples of artificial molecular devices and machines taken from our
      work, which provide a flavour of current research. They are molecular and
      supramolecular systems that operate and/or perform valuable functions by
      exploiting photoinduced energy- or electron-transfer processes,
      photoisomerization reactions, or photoinduced proton transfer. The choice of
      these examples was based on both their intrinsic importance for the referred
      topic and their educational value. In the last section of the review potential
      applications, limitations and future directions of the research in the field of
      artificial molecular devices and machines are also discussed. 

PMID- 24590054
TI  - Influence of acute or chronic administration of ovarian hormones on the effects
      of desipramine in the forced swim test in female rats.
AB  - RATIONALE: Gender may influence antidepressant (AD) treatment outcome. In order
      to address this preclinically, the potential effects of ovarian hormones on AD
      treatment in ovariectomized female rats were investigated. OBJECTIVES: In the
      first study, the effect of acute administration of estrogen and progesterone on
      the antidepressant-like effects of desipramine (DMI), a selective norepinephrine
      reuptake inhibitor (SNRI), was investigated in the forced swimming test (FST). In
      the second study, the effect of chronic administration of these hormones on the
      effects of chronically administered DMI was investigated. RESULTS: In the acute
      study, the hormones blocked the effects of DMI in the FST as demonstrated by the
      absence of either a reduction in immobility or an increase in climbing behavior
      in animals treated with DMI in combination with the hormones. Concentration
      response experiments on hippocampal synaptosomes revealed no changes in the Km or
      Bmax for uptake of (3)H-NE in hormone-treated rats. In the chronic study, the
      antidepressant-like effects of DMI in the FST were not blocked by chronic
      administration of hormones. Interestingly, the hormones affected the serum
      concentrations of DMI. These levels were significantly higher in animals
      receiving 10 or 15 mg/kg/day in hormone-treated rats as compared to those with
      placebo. CONCLUSIONS: Acute administration of hormones blocked the effects of DMI
      (given three times over 24 h) in the FST. However, chronic administration of
      these hormones failed to block the effects of chronically administered DMI (at a
      dose that produces clinically relevant serum concentrations).

PMID- 24590056
TI  - Genetic suppression of inflammation blocks the tumor-promoting effects of TGF
      beta in gastric tissue.
AB  - The contributions of TGF-beta signaling to cancer are complex but involve the
      inflammatory microenvironment as well as cancer cells themselves. In mice
      encoding a TGF-beta mutant that precludes its binding to the latent TGF-beta
      binding protein (Tgfb1(-/C33S)), we observed multiorgan inflammation and an
      elevated incidence of various types of gastrointestinal solid tumors due to
      impaired conversion of latent to active TGF-beta1. By genetically eliminating
      activators of latent TGF-beta1, we further lowered the amount of TGF-beta, which
      enhanced tumor frequency and multiorgan inflammation. This model system was used
      to further investigate the relative contribution of TGF-beta1 to lymphocyte
      mediated inflammation in gastrointestinal tumorigenesis. Toward this end, we
      generated Tgfb1(-/C33S);Rag2(-/-) mice that lacked adaptive immune function,
      which eliminated tumor production. Analysis of tissue from Tgfb1(-/C33S) mice
      indicated decreased levels of P-Smad3 compared with wild-type animals, whereas
      tissue from Tgfb1(-/C33S);Rag2(-/-) mice had normal P-Smad3 levels. Inhibiting
      the inflammatory response normalized levels of interleukin (IL)-1beta and IL-6
      and reduced tumor cell proliferation. In addition, Tgfb1(-/C33S);Rag2(-/-) mice
      exhibited reduced paracrine signaling in the epithelia, mediated by hepatocyte
      growth factor produced by gastric stroma. Together, our results indicate that
      many of the responses of the gastric tissue associated with decreased TGF-beta1
      may be directly or indirectly affected by inflammatory processes, which accompany
      loss of TGF-beta1, rather than a direct effect of loss of the cytokine.

PMID- 24590057
TI  - HO-3867, a safe STAT3 inhibitor, is selectively cytotoxic to ovarian cancer.
AB  - STAT3 is well corroborated preclinically as a cancer therapeutic target, but
      tractable translational strategies for its blockade by small molecule inhibitors
      have remained elusive. In this study, we report the development of a novel class
      of bifunctional STAT3 inhibitors, based on conjugation of a diarylidenyl
      piperidone (DAP) backbone to an N-hydroxypyrroline (-NOH) group, which exhibits
      minimal toxicity against normal cells and good oral bioavailability. Molecular
      modeling studies of this class suggested direct interaction with the STAT3 DNA
      binding domain. In particular, the DAP compound HO-3867 selectively inhibited
      STAT3 phosphorylation, transcription, and DNA binding without affecting the
      expression of other active STATs. HO-3867 exhibited minimal toxicity toward
      noncancerous cells and tissues but induced apoptosis in ovarian cancer cells.
      Pharmacologic analysis revealed greater bioabsorption and bioavailability of the
      active (cytotoxic) metabolites in cancer cells compared with normal cells. The
      selective cytotoxicity of HO-3867 seemed to be multifaceted, eliciting
      differential activation of the Akt pathway in normal versus cancer cells. RNAi
      attenuation experiments confirmed the requirement of STAT3 for HO-3867-mediated
      apoptosis in ovarian cancer cells. In vivo testing showed that HO-3867 could
      block xenograft tumor growth without toxic side effects. Furthermore, in primary
      human ovarian cancer cells isolated from patient ascites, HO-3867 inhibited cell
      migration/invasion and survival. Our results offer preclinical proof-of-concept
      for HO-3867 as a selective STAT3 inhibitor to treat ovarian cancer and other
      solid tumors where STAT3 is widely upregulated.

PMID- 24590058
TI  - STAT3-mediated autophagy dependence identifies subtypes of breast cancer where
      autophagy inhibition can be efficacious.
AB  - Autophagy is a protein and organelle degradation pathway that is involved in
      diverse diseases, including cancer. Recent evidence suggests that autophagy is a
      cell survival mechanism in tumor cells and that its inhibition, especially in
      combination with other therapy, could be beneficial but it remains unclear if all
      cancer cells behave the same way when autophagy is inhibited. We inhibited
      autophagy in a panel of breast cancer cell lines and found that some of them are
      dependent on autophagy for survival even in nutrient rich conditions without any
      additional stress, whereas others need autophagy only when stressed. Survival
      under unstressed conditions is due to cell type-specific autophagy regulation of
      STAT3 activity and this phenotype is enriched in triple-negative cell lines. This
      autophagy-dependency affects response to therapy because autophagy inhibition
      reduced tumor growth in vivo in autophagy-dependent but not in autophagy
      independent breast tumors, whereas combination treatment with autophagy
      inhibitors and other agent was preferentially synergistic in autophagy-dependent
      cells. These results imply that autophagy-dependence represents a tumor cell
      specific characteristic where autophagy inhibition will be more effective.
      Moreover, our results suggest that autophagy inhibition might be a potential
      therapeutic strategy for triple-negative breast cancers, which currently lack an
      effective targeted treatment.

PMID- 24590059
TI  - Immunosurveillance by antiangiogenesis: tumor growth arrest by T cell-derived
      thrombospondin-1.
AB  - Recent advances in cancer immunotherapy suggest that manipulation of the immune
      system to enhance the antitumor response may be a highly effective treatment
      modality. One understudied aspect of immunosurveillance is antiangiogenic
      surveillance, the regulation of tumor angiogenesis by the immune system,
      independent of tumor cell lysis. CD4(+) T cells can negatively regulate
      angiogenesis by secreting antiangiogenic factors such as thrombospondin-1 (TSP
      1). In tumor-bearing mice, we show that a Th1-directed viral infection that
      triggers upregulation of TSP-1 in CD4(+) and CD8(+) T cells can inhibit tumor
      angiogenesis and suppress tumor growth. Using bone marrow chimeras and adoptive T
      cell transfers, we demonstrated that TSP-1 expression in the T-cell compartment
      was necessary and sufficient to inhibit tumor growth by suppressing tumor
      angiogenesis after the viral infection. Our results establish that tumorigenesis
      can be stanched by antiangiogenic surveillance triggered by an acute viral
      infection, suggesting novel immunologic approaches to achieve antiangiogenic
      therapy.

PMID- 24590061
TI  - Direct and indirect air particle cytotoxicity in human alveolar epithelial cells.
AB  - Air particulate matter has been associated with adverse impact on the respiratory
      system leading to cytotoxic and proinflammatory effects. The biological
      mechanisms behind these associations may be initiated by inhaled small size
      particles, particle components (soluble fraction) and/or mediators released by
      particle-exposed cells (conditioned media). The effect of Urban Air Particles
      from Buenos Aires (UAP-BA) and Residual Oil Fly Ash (ROFA) a surrogate of ambient
      air pollution, their Soluble Fractions (SF) and Conditioned Media (CM) on A549
      lung epithelial cells was examined. After 24 h exposure to TP (10 and 100
      MUg/ml), SF or CM, several biological parameters were assayed on cultured A549
      cells. We tested cell viability by MTT, superoxide anion (O2(-)) generation by
      NBT and proinflammatory cytokine (TNFalpha, IL-6 and IL-8) production by ELISA.
      UAP-BA particles or its SF (direct effect) did not modify cell viability and
      generation of O2(-) for any of the doses tested. On the contrary, UAP-BA CM
      (indirect effect) reduced cell viability and increased both generation of O2(-)
      and IL-8 production. Exposure to ROFA particles, SF or ROFA CM reduced
      proliferation and O2(-) but, stimulated IL-8. It is worth to note that UAP-BA and
      ROFA depicted distinct effects on particle-exposed A549 cells implicating
      morphochemical dependence. These in vitro findings support the hypothesis that
      particle-induced lung inflammation and disease may involve lung-derived
      mediators.

PMID- 24590060
TI  - RAE1 ligands for the NKG2D receptor are regulated by STING-dependent DNA sensor
      pathways in lymphoma.
AB  - The immunoreceptor NKG2D originally identified in natural killer (NK) cells
      recognizes ligands that are upregulated on tumor cells. Expression of NKG2D
      ligands (NKG2DL) is induced by the DNA damage response (DDR), which is often
      activated constitutively in cancer cells, revealing them to NK cells as a
      mechanism of immunosurveillance. Here, we report that the induction of retinoic
      acid early transcript 1 (RAE1) ligands for NKG2D by the DDR relies on a STING
      dependent DNA sensor pathway involving the effector molecules TBK1 and IRF3.
      Cytosolic DNA was detected in lymphoma cell lines that express RAE1 and its
      occurrence required activation of the DDR. Transfection of DNA into ligand
      negative cells was sufficient to induce RAE1 expression. Irf3(+/-);EMU-Myc mice
      expressed lower levels of RAE1 on tumor cells and showed a reduced survival rate
      compared with Irf3(+/+);EMU-Myc mice. Taken together, our results suggest that
      genomic damage in tumor cells leads to activation of STING-dependent DNA sensor
      pathways, thereby activating RAE1 and enabling tumor immunosurveillance.

PMID- 24590063
TI  - Impacts of an endoparasitic copepod, Ismaila belciki, on the reproduction, growth
      and survivorship of its nudibranch host, Janolus fuscus.
AB  - Copepods from the genus Ismaila are large endoparasites that inhabit the main
      body cavity and/or cerata of opisthobranch molluscs. These parasites exhibit many
      life history characteristics typically found in parasitic castrators, yet the
      actual impact of infection on reproduction, growth or survivorship of the hosts
      are unknown. On the Oregon (USA) coast, Ismaila belciki can infect over 80% of
      their hermaphroditic hosts, Janolus fuscus. In laboratory mating experiments, we
      compared the reproductive output (egg mass weight, number of egg capsules, number
      of viable embryos) and the gonadal somatic index of infected versus uninfected J.
      fuscus. Infected J. fuscus could produce viable sperm and copulate. Mating with
      an infected individual did not limit a sea slug's reproductive output. However,
      infected J. fuscus had significantly lower reproductive output (by 34-54%),
      producing smaller egg masses with fewer capsules and viable embryos. Infected
      hosts had significantly lower gonadal somatic index than their uninfected
      counterparts, although there was no significant difference in gonadal somatic
      index between hosts with single and double infections. By collecting the egg sacs
      produced by the copepod parasite during experiments, we estimated that 25-34% of
      the host's reproductive output is usurped by the parasite and re-directed to the
      parasite's own reproduction. In the laboratory, infection did not alter growth in
      J. fuscus. However, infection significantly decreased survivorship in mature (but
      not immature) nudibranch hosts. These results suggest that I. belciki is not a
      true castrator, but it does reduce the reproductive output of its host and may
      therefore limit the natural population size of J. fuscus.

PMID- 24590062
TI  - Aldo-keto reductase 7A5 (AKR7A5) attenuates oxidative stress and reactive
      aldehyde toxicity in V79-4 cells.
AB  - Aldo-keto reductase (AKR) enzymes are critical in the detoxification of
      endogenous and exogenous aldehydes. In previous studies, we have shown that
      AKR7A5 enzyme is catalytically active towards aldehydes arising from lipid
      peroxidation (LPO) and that it can significantly protect against 4-hydroxynonenal
      induced apoptosis, suggesting a protective role against the consequences of
      oxidative stress. The aim of this study was to elucidate the cytoprotective
      effect of AKR7A5 against oxidative stress using a transgenic mammalian cell line
      expressing AKR7A5. Results show that expression of AKR7A5 in V79-4 cells provides
      significant protection against the cytotoxicity of H2O2 and menadione, with its
      expression altering the IC50 of H2O2 from 1.1 to 2.3 mM and the IC50 of menadione
      from 8.6 to 9.6 MUM, thus providing direct evidence for its anti-oxidant
      activity. Cells expressing AKR7A5 were also found to be more resistant to several
      LPO-derived aldehydes--trans-2-nonenal, hexanal and methylglyoxal. In addition
      the ability of AKR7A5 to enable the cells to cope with ROS accumulation and
      glutathione depletion was assessed. V79-4 cells overexpressing AKR7A5 were able
      to lower cellular ROS levels following treatment with H2O2 and menadione. AKR7A5
      was also able to maintain cellular glutathione homeostasis in the presence of
      H2O2 and menadione. These findings indicate the importance of AKR7A5 in
      protecting cells from the damaging effects of oxidative stress, and that this
      cytoprotective function is carried out through multiple pathways.

PMID- 24590065
TI  - Enhancement of the magnetocaloric effect driven by changes in the crystal
      structure of Al-doped GGG, Gd3Ga5-xAlxO12 (0 <=x <=5).
AB  - The Gd3Ga5-xAlxO12 (0 <= x <= 5) solid solution has been prepared using ceramic
      synthesis routes and the structural and magnetic properties were investigated
      using x-ray diffraction, magnetic susceptibility, chi, and isothermal
      magnetisation, M(H), measurements. Our results indicate a contraction of the unit
      cell and more significant antiferromagnetic interactions as x increases. Despite
      the decrease in the magnetic polarisation on the application of a field and the
      corresponding decrease in the change in the magnetic entropy, DeltaS, we find
      that Gd3Al5O12 has a significantly higher observed (17%) and theoretical (14%)
      DeltaS per unit mass than Gd3Ga5O12. The theoretical increase in DeltaS per unit
      volume (7%) is offset by the increased antiferromagnetic interactions in
      Gd3Al5O12. The differences in DeltaS are driven by a decrease in both the mass
      and the density as Al ions replace Ga ions. These results highlight the
      importance of changes to the crystal structure when considering materials for
      solid state magnetic cooling. 

PMID- 24590066
TI  - Impact of external flow on the dynamics of swimming microorganisms near surfaces.
AB  - Swimming microorganisms have been previously observed to accumulate along walls
      in confined systems both experimentally and in computer simulations. Here, we use
      computer simulations of dilute populations for a simplified model of an organism
      to calculate the dynamics of swimmers between two walls with an external fluid
      flow. Simulations with and without hydrodynamic interactions (HIs) are used to
      quantify their influence on surface accumulation. We found that the accumulation
      of organisms at the wall is larger when HIs are included. An external fluid flow
      orients the organisms parallel to the fluid flow, which reduces the accumulation
      at the walls. The effect of the flow on the orientations is quantified and
      compared to previous work on upstream swimming of organisms and alignment of
      passive rods in flow. In pressure-driven flow, the zero shear rate at the channel
      center leads to a dip in the concentration of organisms in the center. The
      curvature of this dip is quantified as a function of the flow rate. The fluid
      flow also affects the transport of organisms across the channel from one wall to
      the other. 

PMID- 24590064
TI  - Pannexin1 channels act downstream of P2X 7 receptors in ATP-induced murine T-cell
      death.
AB  - Death of murine T cells induced by extracellular ATP is mainly triggered by
      activation of purinergic P2X 7 receptors (P2X 7Rs). However, a link between P2X
      7Rs and pannexin1 (Panx1) channels, which are non-selective, has been recently
      demonstrated in other cell types. In this work, we characterized the expression
      and cellular distribution of pannexin family members (Panxs 1, 2 and 3) in
      isolated T cells. Panx1 was the main pannexin family member clearly detected in
      both helper (CD4+) and cytotoxic (CD8+) T cells, whereas low levels of Panx2 were
      found in both T-cell subsets. Using pharmacological and genetic approaches, Panx1
      channels were found to mediate most ATP-induced ethidium uptake since this was
      drastically reduced by Panx1 channel blockers (10Panx1, Probenecid and low
      carbenoxolone concentration) and absent in T cells derived from Panx1-/- mice.
      Moreover, electrophysiological measurements in wild-type CD4+ cells treated with
      ATP unitary current events and pharmacological sensitivity compatible with Panx1
      channels were found. In addition, ATP release from T cells treated with 4Br
      A23187, a calcium ionophore, was completely blocked with inhibitors of both
      connexin hemichannels and Panx1 channels. Panx1 channel blockers drastically
      reduced the ATP-induced T-cell mortality, indicating that Panx1 channels mediate
      the ATP-induced T-cell death. However, mortality was not reduced in T cells of
      Panx1-/- mice, in which levels of P2X 7Rs and ATP-induced intracellular free Ca2+
      responses were enhanced suggesting that P2X 7Rs take over Panx1 channels lose
      function in mediating the onset of cell death induced by extracellular ATP.

PMID- 24590067
TI  - Using cell structures to develop functional nanomaterials and nanostructures-
      case studies of actin filaments and microtubules.
AB  - This article is based on the continued development of biologically relevant
      elements (i.e., actin filaments and microtubules in living cells) as building
      blocks to create functional nanomaterials and nanostructures that can then be
      used to manufacture nature-inspired small-scale devices or systems. Here, we
      summarize current progress in the field and focus specifically on processes
      characterized by (1) robustness and ease of use, (2) inexpensiveness, and (3)
      potential expandability to mass production. This article, we believe, will
      provide scientists and engineers with a more comprehensive understanding of how
      to mine biological materials and natural design features to construct functional
      materials and devices. 

PMID- 24590068
TI  - Very small "window of opportunity" for generating CO oxidation-active Au(n) on
      TiO2.
AB  - Recent research in heterogeneous catalysis, especially on size-selected model
      systems under UHV conditions and also in realistic catalytic environments, has
      proved that it is necessary to think in terms of the exact number of atoms when
      it comes to catalyst design. This is of utmost importance if the amount of noble
      metal, gold in particular, is to be reduced for practical reactions like CO
      oxidation. Here it is shown that on TiO2 only Au6 and Au7 clusters are active for
      CO oxidation which holds for the single crystal, thin films, and titania clusters
      deposited on HOPG. Size-selected cluster deposition and TPD methods have been
      employed to investigate the CO oxidation activity of Aun/TiO2 systems which are
      compared to recent results reported by Lee et al. to form a consistent picture in
      which only two species can be regarded as "active". The efficiency of
      investigated Aun/(TiO2)93/HOPG composite materials is attributed to carbon
      assisted oxygen spillover from gold to support particles and across grain
      boundaries. 

PMID- 24590069
TI  - Foxc1 is a critical regulator of haematopoietic stem/progenitor cell niche
      formation.
AB  - Haematopoietic stem and progenitor cells are maintained by special
      microenvironments known as niches in bone marrow. Many studies have identified
      diverse candidate cells that constitute niches for haematopoietic stem cells in
      the marrow, including osteoblasts, endothelial cells, Schwann cells, alpha-smooth
      muscle actin-expressing macrophages and mesenchymal progenitors such as CXC
      chemokine ligand (CXCL)12-abundant reticular (CAR) cells, stem cell factor
      expressing cells, nestin-expressing cells and platelet-derived growth factor
      receptor-alpha (PDGFR-alpha)(+)Sca-1(+)CD45(-)Ter119(-) (PalphaS) cells. However,
      the molecular basis of the formation of the niches remains unclear. Here we find
      that the transcription factor Foxc1 is preferentially expressed in the adipo
      osteogenic progenitor CAR cells essential for haematopoietic stem and progenitor
      cell maintenance in vivo in the developing and adult bone marrow. When Foxc1 was
      deleted in all marrow mesenchymal cells or CAR cells, from embryogenesis onwards,
      osteoblasts appeared normal, but haematopoietic stem and progenitor cells were
      markedly reduced and marrow cavities were occupied by adipocytes (yellow adipose
      marrow) with reduced CAR cells. Inducible deletion of Foxc1 in adult mice
      depleted haematopoietic stem and progenitor cells and reduced CXCL12 and stem
      cell factor expression in CAR cells but did not induce a change to yellow marrow.
      These data suggest a role for Foxc1 in inhibiting adipogenic processes in CAR
      progenitors. Foxc1 might also promote CAR cell development, upregulating CXCL12
      and stem cell factor expression. This study identifies Foxc1 as a specific
      transcriptional regulator essential for development and maintenance of the
      mesenchymal niches for haematopoietic stem and progenitor cells. 

PMID- 24590070
TI  - Structural basis for ubiquitin-mediated antiviral signal activation by RIG-I.
AB  - Ubiquitin (Ub) has important roles in a wide range of intracellular signalling
      pathways. In the conventional view, ubiquitin alters the signalling activity of
      the target protein through covalent modification, but accumulating evidence
      points to the emerging role of non-covalent interaction between ubiquitin and the
      target. In the innate immune signalling pathway of a viral RNA sensor, RIG-I,
      both covalent and non-covalent interactions with K63-linked ubiquitin chains (K63
      Ubn) were shown to occur in its signalling domain, a tandem caspase activation
      and recruitment domain (hereafter referred to as 2CARD). Non-covalent binding of
      K63-Ubn to 2CARD induces its tetramer formation, a requirement for downstream
      signal activation. Here we report the crystal structure of the tetramer of human
      RIG-I 2CARD bound by three chains of K63-Ub2. 2CARD assembles into a helical
      tetramer resembling a 'lock-washer', in which the tetrameric surface serves as a
      signalling platform for recruitment and activation of the downstream signalling
      molecule, MAVS. Ubiquitin chains are bound along the outer rim of the helical
      trajectory, bridging adjacent subunits of 2CARD and stabilizing the 2CARD
      tetramer. The combination of structural and functional analyses reveals that
      binding avidity dictates the K63-linkage and chain-length specificity of 2CARD,
      and that covalent ubiquitin conjugation of 2CARD further stabilizes the Ub-2CARD
      interaction and thus the 2CARD tetramer. Our work provides unique insights into
      the novel types of ubiquitin-mediated signal-activation mechanism, and previously
      unexpected synergism between the covalent and non-covalent ubiquitin interaction
      modes. 

PMID- 24590071
TI  - Apical constriction drives tissue-scale hydrodynamic flow to mediate cell
      elongation.
AB  - Epithelial folding mediated by apical constriction converts flat epithelial
      sheets into multilayered, complex tissue structures and is used throughout
      development in most animals. Little is known, however, about how forces produced
      near the apical surface of the tissue are transmitted within individual cells to
      generate the global changes in cell shape that characterize tissue deformation.
      Here we apply particle tracking velocimetry in gastrulating Drosophila embryos to
      measure the movement of cytoplasm and plasma membrane during ventral furrow
      formation. We find that cytoplasmic redistribution during the lengthening phase
      of ventral furrow formation can be precisely described by viscous flows that
      quantitatively match the predictions of hydrodynamics. Cell membranes move with
      the ambient cytoplasm, with little resistance to, or driving force on, the flow.
      Strikingly, apical constriction produces similar flow patterns in mutant embryos
      that fail to form cells before gastrulation ('acellular' embryos), such that the
      global redistribution of cytoplasm mirrors the summed redistribution occurring in
      individual cells of wild-type embryos. Our results indicate that during the
      lengthening phase of ventral furrow formation, hydrodynamic behaviour of the
      cytoplasm provides the predominant mechanism transmitting apically generated
      forces deep into the tissue and that cell individualization is dispensable. 

PMID- 24590072
TI  - Direct measurement of local oxygen concentration in the bone marrow of live
      animals.
AB  - Characterization of how the microenvironment, or niche, regulates stem cell
      activity is central to understanding stem cell biology and to developing
      strategies for the therapeutic manipulation of stem cells. Low oxygen tension
      (hypoxia) is commonly thought to be a shared niche characteristic in maintaining
      quiescence in multiple stem cell types. However, support for the existence of a
      hypoxic niche has largely come from indirect evidence such as proteomic analysis,
      expression of hypoxia inducible factor-1alpha (Hif-1alpha) and related genes, and
      staining with surrogate hypoxic markers (for example, pimonidazole). Here we
      perform direct in vivo measurements of local oxygen tension (pO2) in the bone
      marrow of live mice. Using two-photon phosphorescence lifetime microscopy, we
      determined the absolute pO2 of the bone marrow to be quite low (<32 mm Hg)
      despite very high vascular density. We further uncovered heterogeneities in local
      pO2, with the lowest pO2 (~9.9 mm Hg, or 1.3%) found in deeper peri-sinusoidal
      regions. The endosteal region, by contrast, is less hypoxic as it is perfused
      with small arteries that are often positive for the marker nestin. These pO2
      values change markedly after radiation and chemotherapy, pointing to the role of
      stress in altering the stem cell metabolic microenvironment. 

PMID- 24590073
TI  - Protection against filovirus diseases by a novel broad-spectrum nucleoside
      analogue BCX4430.
AB  - Filoviruses are emerging pathogens and causative agents of viral haemorrhagic
      fever. Case fatality rates of filovirus disease outbreaks are among the highest
      reported for any human pathogen, exceeding 90% (ref. 1). Licensed therapeutic or
      vaccine products are not available to treat filovirus diseases. Candidate
      therapeutics previously shown to be efficacious in non-human primate disease
      models are based on virus-specific designs and have limited broad-spectrum
      antiviral potential. Here we show that BCX4430, a novel synthetic adenosine
      analogue, inhibits infection of distinct filoviruses in human cells. Biochemical,
      reporter-based and primer-extension assays indicate that BCX4430 inhibits viral
      RNA polymerase function, acting as a non-obligate RNA chain terminator. Post
      exposure intramuscular administration of BCX4430 protects against Ebola virus and
      Marburg virus disease in rodent models. Most importantly, BCX4430 completely
      protects cynomolgus macaques from Marburg virus infection when administered as
      late as 48 hours after infection. In addition, BCX4430 exhibits broad-spectrum
      antiviral activity against numerous viruses, including bunyaviruses,
      arenaviruses, paramyxoviruses, coronaviruses and flaviviruses. This is the first
      report, to our knowledge, of non-human primate protection from filovirus disease
      by a synthetic drug-like small molecule. We provide additional pharmacological
      characterizations supporting the potential development of BCX4430 as a
      countermeasure against human filovirus diseases and other viral diseases
      representing major public health threats. 

PMID- 24590076
TI  - Psychometric properties of the Emotion Understanding Assessment with Spanish- and
      English-speaking preschoolers attending Head Start.
AB  - The Emotion Understanding Assessment (EUA) is based on a theoretical model of
      recognizing emotion expressions and reasoning about situation-based, desire
      based, and belief-based emotions. While research has noted that emotion
      understanding predicts current and future social and academic functioning, little
      is known about the psychometric properties of the EUA. This research sought to
      test the EUA factor structure and measurement invariance across gender, across
      language (English and Spanish speakers), and over time (24 weeks) in 281
      preschoolers attending Head Start. Results indicated that a two-factor model of
      emotion expression recognition and emotional perspective taking of the EUA fit
      the data for the total sample, for each group (gender and language), and at each
      time point. Furthermore, configural and scalar invariance of the EUA was
      demonstrated across gender, language, and time. These results offer support that
      the EUA is assessing emotion expression recognition and emotional perspective
      taking constructs equivalently in boy, girls, Spanish and English speakers, and
      over time. Examination of latent means across groups and time indicate no
      differences in emotion understanding based on gender or language or over the 24
      week time frame in this sample of preschoolers attending Head Start. 

PMID- 24590077
TI  - Grooved pegboard predicates more of cognitive than motor involvement in
      Parkinson's disease.
AB  - The Grooved Pegboard Test (GPT) was conceived as a test of manual dexterity,
      upper-limb motor speed, and hand-eye coordination. The aim of our study was to
      test the componential structure of the GPT on an archetypal model of motor
      impairment, Parkinson's disease (PD). A total of 45 PD patients (33 males, 12
      females; age M = 67, range = 49-81; PD duration M = 10, range = 6-20 years; H/Y
      stage 2, range = 2-3) and 20 age- and education-matched controls (14 males, 6
      females; age M = 66, range = 48-80) were included. All participants were
      investigated using the GPT, Short Falls Efficacy Scale-International, Frontal
      Assessment Battery (FAB), Montreal Cognitive Assessment (MoCA), and Non-Motor
      Symptom Scale. Patients were followed for 6 months, using fall diaries and
      monthly phone calls to define PD fallers (falls >= 1; n = 27) and PD nonfallers
      (falls = 0; n = 18). Using structural equation modeling, the GPT predicted
      performance on the MoCA (p < .001), but not on the FAB (p = .29). In conclusion,
      analysis of the structure of the GPT provided evidence about important cognitive
      features, in addition to the motor component of this test in PD. 

PMID- 24590075
TI  - ZMYND11 links histone H3.3K36me3 to transcription elongation and tumour
      suppression.
AB  - Recognition of modified histones by 'reader' proteins plays a critical role in
      the regulation of chromatin. H3K36 trimethylation (H3K36me3) is deposited onto
      the nucleosomes in the transcribed regions after RNA polymerase II elongation. In
      yeast, this mark in turn recruits epigenetic regulators to reset the chromatin to
      a relatively repressive state, thus suppressing cryptic transcription. However,
      much less is known about the role of H3K36me3 in transcription regulation in
      mammals. This is further complicated by the transcription-coupled incorporation
      of the histone variant H3.3 in gene bodies. Here we show that the candidate
      tumour suppressor ZMYND11 specifically recognizes H3K36me3 on H3.3 (H3.3K36me3)
      and regulates RNA polymerase II elongation. Structural studies show that in
      addition to the trimethyl-lysine binding by an aromatic cage within the PWWP
      domain, the H3.3-dependent recognition is mediated by the encapsulation of the
      H3.3-specific 'Ser 31' residue in a composite pocket formed by the tandem bromo
      PWWP domains of ZMYND11. Chromatin immunoprecipitation followed by sequencing
      shows a genome-wide co-localization of ZMYND11 with H3K36me3 and H3.3 in gene
      bodies, and its occupancy requires the pre-deposition of H3.3K36me3. Although
      ZMYND11 is associated with highly expressed genes, it functions as an
      unconventional transcription co-repressor by modulating RNA polymerase II at the
      elongation stage. ZMYND11 is critical for the repression of a transcriptional
      program that is essential for tumour cell growth; low expression levels of
      ZMYND11 in breast cancer patients correlate with worse prognosis. Consistently,
      overexpression of ZMYND11 suppresses cancer cell growth in vitro and tumour
      formation in mice. Together, this study identifies ZMYND11 as an H3.3-specific
      reader of H3K36me3 that links the histone-variant-mediated transcription
      elongation control to tumour suppression. 

PMID- 24590079
TI  - [Evidence-based recommendations for the management of undifferentiated peripheral
      inflammatory arthritis (UPIA). The German perspective on the international 3e
      initiative].
AB  - INTRODUCTION: Peripheral arthritis is the most common presenting complaint in
      clinical rheumatology. Unequivocal identification of the underlying entity can be
      difficult, particularly at an early stage. Such cases are commonly referred to as
      undifferentiated peripheral inflammatory arthritis (UPIA). Since evidence-based
      recommendations for the clinical management of UPIA are lacking, this
      international 3e initiative convened 697 rheumatologists from 17 countries to
      develop appropriate recommendations. METHODS: Based on a systematic literature
      research in Medline, EMBASE, Cochrane Library, and the ACR/EULAR abstracts of
      2007/2008, 10 multinational recommendations were developed by 3 rounds of a
      Delphi process. In Germany, a national group of experts worked on 3 additional
      recommendations using the same method. The recommendations were discussed among
      the members of the 3e initiative and the degree of consensus was analyzed as well
      as the potential impact of the recommendations on clinical practice. RESULTS: A
      total of 39,756 references were identified, of which 250 were systematically
      reviewed for the development of 10 multinational recommendations concerning
      differential diagnosis, diagnostic and prognostic value of clinical assessments,
      laboratory tests and imaging techniques, and monitoring of UPIA. In addition, 3
      national recommendations on the diagnostic and prognostic value of a response to
      anti-inflammatory therapy on the analysis of synovial fluid and on enthesitis
      were developed by the German experts based on 35 out of 5542 references.
      CONCLUSIONS: The article translates the 2011 published original paper of the
      international 3e initiative (Machado et al., Ann Rheum Dis 70:15-24, 2011) and
      reports the methods and results of the national vote and the additional 3
      national recommendations.

PMID- 24590082
TI  - Decrease the incentives to order lipid panels.

PMID- 24590083
TI  - Decrease the incentives to order lipid panels--reply.

PMID- 24590084
TI  - Patient-centered decisions in primary care: from necessity to realism.

PMID- 24590085
TI  - Acutely ill patients will likely benefit from more monitoring, not less.

PMID- 24590086
TI  - Patient-centered decisions in primary care--reply.

PMID- 24590087
TI  - Acutely ill patients will likely benefit from more monitoring, not less--reply.

PMID- 24590088
TI  - Privacy protection during internet search for health-related information.

PMID- 24590074
TI  - Developmental pathway for potent V1V2-directed HIV-neutralizing antibodies.
AB  - Antibodies capable of neutralizing HIV-1 often target variable regions 1 and 2
      (V1V2) of the HIV-1 envelope, but the mechanism of their elicitation has been
      unclear. Here we define the developmental pathway by which such antibodies are
      generated and acquire the requisite molecular characteristics for neutralization.
      Twelve somatically related neutralizing antibodies (CAP256-VRC26.01-12) were
      isolated from donor CAP256 (from the Centre for the AIDS Programme of Research in
      South Africa (CAPRISA)); each antibody contained the protruding tyrosine
      sulphated, anionic antigen-binding loop (complementarity-determining region (CDR)
      H3) characteristic of this category of antibodies. Their unmutated ancestor
      emerged between weeks 30-38 post-infection with a 35-residue CDR H3, and
      neutralized the virus that superinfected this individual 15 weeks after initial
      infection. Improved neutralization breadth and potency occurred by week 59 with
      modest affinity maturation, and was preceded by extensive diversification of the
      virus population. HIV-1 V1V2-directed neutralizing antibodies can thus develop
      relatively rapidly through initial selection of B cells with a long CDR H3, and
      limited subsequent somatic hypermutation. These data provide important insights
      relevant to HIV-1 vaccine development. 

PMID- 24590089
TI  - Management of critically ill patients: the less intensive the treatment, the more
      vigilance demanded.

PMID- 24590090
TI  - Privacy protection during internet search for health-related information--reply.

PMID- 24590091
TI  - Management of critically ill patients-reply.

PMID- 24590092
TI  - Assessment and management of back pain.

PMID- 24590093
TI  - Assessment and management of back pain.

PMID- 24590094
TI  - Assessment and management of back pain--reply.

PMID- 24590095
TI  - Mortality and timing of surgery for prosthetic valve endocarditis.

PMID- 24590096
TI  - Mortality and timing of surgery for prosthetic valve endocarditis--reply.

PMID- 24590097
TI  - Caution warranted when defining contraindications in initiating beta-blocker
      therapy.

PMID- 24590098
TI  - Caution warranted when defining contraindications in initiating beta-blocker
      therapy--reply.

PMID- 24590099
TI  - Colonoscopy--don't want to be sedated?

PMID- 24590100
TI  - The efficacy of screening colonoscopy.

PMID- 24590101
TI  - The efficacy of screening colonoscopy--reply.

PMID- 24590106
TI  - Quantitative determination of beta-hydroxymethylbutyrate and leucine in culture
      media and microdialysates from rat brain by UHPLC-tandem mass spectrometry.
AB  - The main objective of the present work was to develop a method to determine beta
      hydroxymethylbutyrate (HMB) and leucine (Leu) in culture media and brain
      microdialysates. An accurate, selective, and cost-effective method, based on the
      use of ultrahigh-performance liquid chromatography-tandem mass spectrometry
      (UHPLC-MS/MS), was developed for the identification and quantification of both
      compounds. The method consisted of sample dilution, direct injection onto the
      chromatographic equipment, and quantification with a triple quadrupole mass
      spectrometer using an electrospray ionization interface in positive mode. The
      procedure and the UHPLC-MS/MS parameters were accurately optimized to achieve the
      highest recoveries and to enhance the analytical characteristics of the method.
      For chromatographic separation, an Acquity UPLC BEH Hilic column using
      acetonitrile-water gradient with formic acid as additive was employed. The total
      run time was 4 min. The limits of detection (LODs) obtained ranged from 0.01 to
      0.04 MUg mL(-1), and the limits of quantification (LOQs) ranged from 0.04 to 0.12
      MUg mL(-1). Precision (expressed as relative standard deviation) was lower than
      15 %, and the determination coefficient (R (2)) was higher than 99.0 % with a
      residual deviation for each calibration point lower than +/-25 %. Mean recoveries
      were between 85 and 115 %. The method was successfully applied to the analysis of
      both compounds, HMB and Leu, in samples obtained from an experiment of blood
      brain barrier (BBB) passage in vitro and to an experiment of brain microdialysis
      in rats in vivo after an oral challenge with HMB to detect its appearance in the
      brain.

PMID- 24590107
TI  - Development, validation, and application of a novel LC-MS/MS trace analysis
      method for the simultaneous quantification of seven iodinated X-ray contrast
      media and three artificial sweeteners in surface, ground, and drinking water.
AB  - A new method for the simultaneous determination of iodated X-ray contrast media
      (ICM) and artificial sweeteners (AS) by liquid chromatography-tandem mass
      spectrometry (LC-MS/MS) operated in positive and negative ionization switching
      mode was developed. The method was validated for surface, ground, and drinking
      water samples. In order to gain higher sensitivities, a 10-fold sample enrichment
      step using a Genevac EZ-2 plus centrifugal vacuum evaporator that provided
      excellent recoveries (90 +/- 6 %) was selected for sample preparation. Limits of
      quantification below 10 ng/L were obtained for all compounds. Furthermore, sample
      preparation recoveries and matrix effects were investigated thoroughly for all
      matrix types. Considerable matrix effects were observed in surface water and
      could be compensated by the use of four stable isotope-labeled internal
      standards. Due to their persistence, fractions of diatrizoic acid, iopamidol, and
      acesulfame could pass the whole drinking water production process and were
      observed also in drinking water. To monitor the fate and occurrence of these
      compounds, the validated method was applied to samples from different stages of
      the drinking water production process of the Industrial Works of Basel (IWB).
      Diatrizoic acid was found as the most persistent compound which was eliminated by
      just 40 % during the whole drinking water treatment process, followed by
      iopamidol (80 % elimination) and acesulfame (85 % elimination). All other
      compounds were completely restrained and/or degraded by the soil and thus were
      not detected in groundwater. Additionally, a direct injection method without
      sample preparation achieving 3-20 ng/L limits of quantification was compared to
      the developed method. 

PMID- 24590109
TI  - High genetic stability of peroral infection factors from Anticarsia gemmatalis
      MNPV over 20years of sampling.
AB  - The Anticarsia gemmatalis multiple nucleopolyhedrovirus (AgMNPV) has been used as
      a biopesticide since the early 1980s in Brazil to control the major pest of
      soybean crops, the velvetbean caterpillar, Anticarsia gemmatalis. To monitor the
      genetic diversity over space and time we sequenced four pif genes (pif1, pif2,
      pif3 and pif4) from AgMNPV isolates collected from different regions of South
      America, as well as of seasonal isolates, sampled during a two-decade field
      experiment. Although all genes presented low levels of polymorphism, the pif-2
      carries a slightly higher number of polymorphic sites. Overall, this study
      reveals that pif genes have remained stable after 20 years of repeated field
      application.

PMID- 24590108
TI  - Association and interaction analyses of 5-HT3 receptor and serotonin transporter
      genes with alcohol, cocaine, and nicotine dependence using the SAGE data.
AB  - Previous studies have implicated genes encoding the 5-HT3AB receptors (HTR3A and
      HTR3B) and the serotonin transporter (SLC6A4), both independently and
      interactively, in alcohol (AD), cocaine (CD), and nicotine dependence (ND).
      However, whether these genetic effects also exist in subjects with comorbidities
      remains largely unknown. We used 1,136 African-American (AA) and 2,428 European
      American (EA) subjects from the Study of Addiction: Genetics and Environment
      (SAGE) to determine associations between 88 genotyped or imputed variants within
      HTR3A, HTR3B, and SLC6A4 and three types of addictions, which were measured by
      DSM-IV diagnoses of AD, CD, and ND and the Fagerstrom Test for Nicotine
      Dependence (FTND), an independent measure of ND commonly used in tobacco
      research. Individual SNP-based association analysis revealed a significant
      association of rs2066713 in SLC6A4 with FTND in AA (beta = -1.39; P = 1.6E - 04).
      Haplotype-based association analysis found one major haplotype formed by SNPs
      rs3891484 and rs3758987 in HTR3B that was significantly associated with AD in the
      AA sample, and another major haplotype T-T-G, formed by SNPs rs7118530,
      rs12221649, and rs2085421 in HTR3A, which showed significant association with
      FTND in the EA sample. Considering the biologic roles of the three genes and
      their functional relations, we used the GPU-based Generalized Multifactor
      Dimensionality Reduction (GMDR-GPU) program to test SNP-by-SNP interactions
      within the three genes and discovered two- to five-variant models that have
      significant impacts on AD, CD, ND, or FTND. Interestingly, most of the SNPs
      included in the genetic interaction model(s) for each addictive phenotype are
      either overlapped or in high linkage disequilibrium for both AA and EA samples,
      suggesting these detected variants in HTR3A, HTR3B, and SLC6A4 are interactively
      contributing to etiology of the three addictive phenotypes examined in this
      study.

PMID- 24590110
TI  - Systematically extracting metal- and solvent-related occupational information
      from free-text responses to lifetime occupational history questionnaires.
AB  - OBJECTIVES: Lifetime occupational history (OH) questionnaires often use open
      ended questions to capture detailed information about study participants' jobs.
      Exposure assessors use this information, along with responses to job- and
      industry-specific questionnaires, to assign exposure estimates on a job-by-job
      basis. An alternative approach is to use information from the OH responses and
      the job- and industry-specific questionnaires to develop programmable decision
      rules for assigning exposures. As a first step in this process, we developed a
      systematic approach to extract the free-text OH responses and convert them into
      standardized variables that represented exposure scenarios. METHODS: Our study
      population comprised 2408 subjects, reporting 11991 jobs, from a case-control
      study of renal cell carcinoma. Each subject completed a lifetime OH questionnaire
      that included verbatim responses, for each job, to open-ended questions including
      job title, main tasks and activities (task), tools and equipment used (tools),
      and chemicals and materials handled (chemicals). Based on a review of the
      literature, we identified exposure scenarios (occupations, industries,
      tasks/tools/chemicals) expected to involve possible exposure to chlorinated
      solvents, trichloroethylene (TCE) in particular, lead, and cadmium. We then used
      a SAS macro to review the information reported by study participants to identify
      jobs associated with each exposure scenario; this was done using previously coded
      standardized occupation and industry classification codes, and a priori lists of
      associated key words and phrases related to possibly exposed tasks, tools, and
      chemicals. Exposure variables representing the occupation, industry, and
      task/tool/chemicals exposure scenarios were added to the work history records of
      the study respondents. Our identification of possibly TCE-exposed scenarios in
      the OH responses was compared to an expert's independently assigned probability
      ratings to evaluate whether we missed identifying possibly exposed jobs. RESULTS:
      Our process added exposure variables for 52 occupation groups, 43 industry
      groups, and 46 task/tool/chemical scenarios to the data set of OH responses.
      Across all four agents, we identified possibly exposed task/tool/chemical
      exposure scenarios in 44-51% of the jobs in possibly exposed occupations.
      Possibly exposed task/tool/chemical exposure scenarios were found in a nontrivial
      9-14% of the jobs not in possibly exposed occupations, suggesting that our
      process identified important information that would not be captured using
      occupation alone. Our extraction process was sensitive: for jobs where our
      extraction of OH responses identified no exposure scenarios and for which the
      sole source of information was the OH responses, only 0.1% were assessed as
      possibly exposed to TCE by the expert. CONCLUSIONS: Our systematic extraction of
      OH information found useful information in the task/chemicals/tools responses
      that was relatively easy to extract and that was not available from the
      occupational or industry information. The extracted variables can be used as
      inputs in the development of decision rules, especially for jobs where no
      additional information, such as job- and industry-specific questionnaires, is
      available.

PMID- 24590111
TI  - Biomarkers: a proteomic challenge. Preface.

PMID- 24590112
TI  - Structural characterization of a neuroblast-specific phosphorylated region of
      MARCKS.
AB  - MARCKS (Myristoylated Alanine-Rich C Kinase substrate) is a natively unfolded
      protein that interacts with actin, Ca(2+)-Calmodulin, and some plasma membrane
      lipids. Such interactions occur at a highly conserved region that is specifically
      phosphorylated by PKC: the Effector Domain. There are two other conserved
      domains, MH1 (including a myristoylation site) and MH2, also located in the amino
      terminal region and whose structure and putative protein binding capabilities are
      currently unknown. MH2 sequence contains a serine that we described as being
      phosphorylated only in differentiating neurons (S25 in chick). Here, Circular
      Dichroism (CD) and Nuclear Magnetic Resonance (NMR) spectroscopy were used to
      characterize the phosphorylated and unphosphorylated forms of a peptide with the
      MARCKS sequence surrounding S25. The peptide phosphorylated at this residue is
      recognized by monoclonal antibody 3C3 (mAb 3C3). CD and NMR data indicated that
      S25 phosphorylation does not cause extensive modifications in the peptide
      structure. However, the sharper lines, the absence of multiple spin systems and
      relaxation dispersion data observed for the phosphorylated peptide suggested a
      more ordered structure. Surface Plasmon Resonance was employed to compare the
      binding properties of mAb 3C3 to MARCKS protein and peptide. SPR showed that mAb
      3C3 binds to the whole protein and the peptide with a similar affinity, albeit
      different kinetics. The slightly ordered structure of the phosphorylated peptide
      might be at the origin of its ability to interact with mAb 3C3 antibody, but this
      binding did not noticeably modify the peptide structure. 

PMID- 24590113
TI  - Molecular bases of protein halotolerance.
AB  - Halophilic proteins are stable and function at high salt concentration.
      Understanding how these molecules maintain their fold stable and avoid
      aggregation under harsh conditions is of great interest for biotechnological
      applications. This mini-review describes what is known about the molecular
      determinants of protein halotolerance. Comparisons between the sequences of
      halophilic/non-halophilic homologous protein pairs indicated that Asp and Glu are
      significantly more frequent, while Lys, Ile and Leu are less frequent in
      halophilic proteins. Homologous halophilic and non-halophilic proteins have
      similar overall structure, secondary structure content, and number of residues
      involved in the formation of H-bonds. On the other hand, on the halophilic
      protein surface, a decrease of nonpolar residues and an increase of charged
      residues are observed. Particularly, halophilic adaptation correlates with an
      increase of Asp and Glu, compensated by a decrease of basic residues, mainly Lys,
      on protein surface. A thermodynamic model, that provides a reliable explanation
      of the salt effect on the conformational stability of globular proteins, is
      presented. 

PMID- 24590114
TI  - Differences in heat stability and ligand binding among beta-lactoglobulin genetic
      variants A, B and C using (1)H NMR and fluorescence quenching.
AB  - The structure of beta-lactoglobulin (beta-LG) is well characterized, but the
      exact location of binding sites for retinol and (-)-epigallocatechingallate
      (EGCG) is still a subject of controversy. Here we report that the genetic beta-LG
      variants A, B and C have different numbers of binding sites for retinol (almost
      completely incorporated into the calyx), as well as for EGCG (exclusively bound
      on the surface), and beta-LG A with the most binding sites for EGCG, which
      include Tyr(20), Phe(151) and His(59). Upon heat related unfolding, new
      unspecific binding sites emerge, which are comparable in number and affinity for
      retinol and for EGCG, and in the three genetic variants A, B and C. The findings
      of our study provide new insights into the use of beta-LG as nanotransporter. 

PMID- 24590115
TI  - Advances in radical probe mass spectrometry for protein footprinting in chemical
      biology applications.
AB  - Radical Probe Mass Spectrometry (RP-MS), first introduced in 1999, utilizes
      hydroxyl radicals generated directly within aqueous solutions using synchrotron
      radiolysis, electrical discharge, and photochemical laser sources to probe
      protein structures and their interactions. It achieves this on millisecond and
      submillisecond timescales that can be used to capture protein dynamics and
      folding events. Hydroxyl radicals are ideal probes of solvent accessibility as
      their size approximates a water molecule. Their high reactivity results in
      oxidation at a multitude of amino acid side chains providing greater structural
      information than a chemical cross-linker that reacts with only one or few
      residues. The oxidation of amino acid side chains occurs at rates in accord with
      the solvent accessibility of the residue so that the extent of oxidation can be
      quantified to reveal a three-dimensional map or footprint of the protein's
      surface. Mass spectrometry is central to this analysis of chemical oxidative
      labelling. This tutorial review, some 15 years on from the first reports,
      highlights the development and significant growth of the application of RP-MS
      including its validation and utility with ion-mobility mass spectrometry (IM-MS),
      the use of RP-MS data to help model protein complexes, studies of the onset of
      oxidative damage, and more recent advances that enable high throughput
      applications through simultaneous protein oxidation and on-plate deposition. The
      accessibility of the RP-MS technology, by means of a modified electrospray
      ionization source, enables the approach to be implemented in many laboratories to
      address a wide range of applications in chemical biology. 

PMID- 24590116
TI  - Shiga toxin and beta-lactamases genes in Escherichia coli phylotypes isolated
      from carcasses of broiler chickens slaughtered in Iran.
AB  - Two hundred and four Escherichia coli strains were isolated from external and
      visceral cavity surfaces of 102 slaughtered broiler carcasses. The isolates were
      screened to determine the phylogenetic background and presence of Shiga toxins
      (stx1, stx2), intimin (eae) and beta-lactamase (blaTEM, blaSHV) genes.
      Phylotyping results revealed that the E. coli isolates segregated in four
      phylogenetic groups A (56.86%), B1 (19.12%), B2 (4.90%) and D (19.12%). PCR
      assays revealed that 13 isolates (6.37%) from 12 carcasses were positive for eae
      (12 isolates) and/or stx2 (2) genes. The eae positive isolates belonged to
      phylogenetic groups A (A0, A1), B1, B2 (B22) and D (D2). Two stx2 positive and
      seven eae positive isolates were recovered from visceral cavity surface, whereas
      only 5 eae positive isolates were from the external surface of the carcasses. On
      the other hand, thirty one E. coli strains isolated from visceral cavity and
      external surface of 26 carcasses carried the blaTEM (27) and blaSHV (4) genes and
      belonged to different phylo-groups. This study suggests that broiler carcasses
      could be considered as an important source of EPEC and STEC pathotypes in
      southeast of Iran; as well as the examined antibiotic resistance genes, which
      were carried by some isolates and could be transferred to pathogens through the
      food chain.

PMID- 24590117
TI  - CO2 laser-assisted deep sclerectomy in glaucoma patients.
AB  - PURPOSE: To evaluate the safety and efficacy of CO2 laser-assisted deep
      sclerectomy surgery (CLASS) in patients with open angle glaucoma. DESIGN: A
      prospective single-arm, nonrandomized clinical investigation for the evaluation
      of technology. METHODS: Fifteen eyes of 15 consecutive patients diagnosed with
      either primary open angle glaucoma or pseudoexfoliation glaucoma who were the
      candidates for glaucoma filtration surgery were included. Laser-assisted deep
      sclerectomy using a CO2 laser system was performed in all patients. A half
      thickness scleral flap was created, the use of 0.04% mitomycin C for 60 seconds
      was left at the surgeon's discretion, and a CO2 laser with a beam-manipulating
      system was used to achieve deep scleral ablation and unroofing of Schlemm's canal
      zone. Visual acuity, complete ophthalmologic examination, and intraocular
      pressure (IOP) were measured and documented at baseline, 1, 2, 4, and 6 weeks and
      at 3, 6, and 12 months, respectively. Complete success was defined as 5<=IOP<=21
      mm Hg and 20% IOP reduction with no medication at the 12-month endpoint visit.
      Qualified success was defined as a similar IOP reduction with medication.
      RESULTS: The preoperative IOP of 27.3+/-4.2 mm Hg (mean+/-SD) dropped to 15.0+/
      3.7 mm Hg at 6 months and 16.6+/-3.4 mm Hg at 12 months postoperatively, yielding
      an average IOP reductions at 6 and 12 months of 13.1+/-4.3 mm Hg (45.1%; 95% CI,
      11, 15.3) and 11.5+/-5.5 mm Hg (39.2%; 95% CI, 8.8, 14.3), respectively
      (P<0.001). The complete success rate after 12 months was 45.5%, whereas qualified
      success was 90.9%. Mitomycin C was used in 76.9% of the CLASS subjects.

PMID- 24590118
TI  - Changes in intraocular pressure and associated systemic factors over 10 years in
      subjects without ocular disease at baseline.
AB  - PURPOSE: To investigate the changes in intraocular pressure (IOP) and associated
      factors over 10 years in subjects who participated in health examinations in 1999
      and 2008. SUBJECTS AND METHODS: Subjects with no clear history of ocular disease
      and who participated in health examinations at Yamanashi Koseiren Health Care
      Center, Japan, in 1999 and 2008 were enrolled in this study. IOP was evaluated
      using a noncontact tonometer. The right eye was analyzed in all subjects. The
      change in IOP between the 2 examinations and the factors that were significantly
      associated with the change in IOP were investigated. RESULTS: A total of 3785
      subjects were enrolled (mean age, 50.9+/-8.6 y), comprising 2022 males (mean age,
      50.3+/-8.9 y) and 1763 females (mean age, 51.5+/-8.2 y). The mean IOPs of males
      and females in 1999 were 13.4+/-3.1 and 12.8+/-2.8 mm Hg, respectively
      (P<0.0001). IOP measured in 2008 was significantly lower than that in 1998 in
      males and females (mean change, -0.8 and -0.6 mm Hg, respectively; P<0.0001).
      Univariate regression analysis showed that changes in systolic blood pressure,
      diastolic blood pressure, total cholesterol, body mass index, and gamma-glutamyl
      transpeptidase were positively correlated with change in IOP. Multivariate
      regression analysis showed that the change in IOP was positively associated with
      the changes in systolic blood pressure, diastolic blood pressure, and body mass
      index. CONCLUSIONS: IOP decreased significantly with age. Several systemic
      factors were significantly correlation with the change in IOP.

PMID- 24590119
TI  - Initial stage of growth of single-walled carbon nanotubes: modeling and
      simulations.
AB  - Because there are different pathways to grow carbon nanotubes (CNTs), a common
      mechanism for the synthesis of CNTs does not likely exist. However, after carbon
      atoms are liberated from carbon-containing precursors by catalysts or from pure
      carbon systems, a common feature, the nucleation of CNTs by electron mediation,
      does appear. We studied this feature using the initial stage of growth of single
      wall CNTs (SWCNTs) by transition metal nano-particle catalysts as the working
      example. To circumvent the bottleneck due to the size and simulation time, we
      used a model in which the metal droplet is represented by a jellium, and the
      effect of collisions between the carbon atoms and atoms of the catalyst is
      captured by charge transfers between the jellium and the carbon. The simulations
      were performed using a transferable semi-empirical Hamiltonian to model the
      interactions between carbon atoms in jellium. We annealed different initial
      configurations of carbon clusters in jellium as well as in a vacuum. We found
      that in jellium, elongated open tubular structures, precursors to the growth of
      SWCNTs, are formed. Our model was also shown to be capable of mimicking the
      continued growth when more atoms were placed near the open end of the tubular
      structure. 

PMID- 24590122
TI  - Magnetic ordering in TmGa.
AB  - We have determined the magnetic structure of the intermetallic compound TmGa by
      high-resolution neutron powder diffraction and (169)Tm Mossbauer spectroscopy.
      This compound crystallizes in the orthorhombic (Cmcm) CrB-type structure and its
      magnetic structure is characterized by magnetic order of the Tm sublattice along
      the a-axis. The initial magnetic ordering occurs at 15(1) K and yields an
      incommensurate antiferromagnetic structure described by the propagation vector k1
      = [0 0.275(2) 0]. At 12 K the dominant ferromagnetic ordering of the Tm
      sublattice along the a-axis develops in what appears to be a first-order
      transition. At 3 K the magnetic structure of TmGa is predominantly ferromagnetic
      but a weakened incommensurate component remains. The ferromagnetic Tm moment
      reaches 6.7(2) MUB at 3 K and the amplitude of the remaining incommensurate
      component is 2.7(4) MUB. The (169)Tm hyperfine magnetic field at 5 K is 631(1) T.

PMID- 24590121
TI  - Comparative evaluation of strategies for quantifying signaling pathway proteins
      in Ewing sarcoma.
AB  - Targeted therapies are increasingly being evaluated for patients with Ewing
      sarcoma (EWS). Optimal strategies for quantifying key signaling proteins in EWS
      remain unclear. We sought to quantify tumor expression of signaling pathway
      proteins in EWS using 3 methodologies. A total of 46 blocks of formalin-fixed
      paraffin-embedded tissue were obtained from 40 patients with EWS. Tumor was
      evaluated for the expression of proteins in the insulin-like growth factor type 1
      receptor (IGF-1R), epithelial growth factor receptor (EGFR), and mTOR pathways
      using standard immunohistochemical analysis (IHC), automated quantitative
      analysis (AQUA) immunohistochemical analysis, and mass spectrometry
      quantification. The mean age at diagnosis was 14 years (range, 1 to 49 y). About
      67.5% were male and 57.5% had localized disease. Samples displayed a wide range
      of expression by AQUA: mean (range) IGF-1R=10,702 (393 to 14,424); EGFR=2750 (672
      to 9798); and phosphatase and tensin homolog (PTEN)=2250 (251 to 6557). Mean IGF
      1R expression by AQUA did not differ between standard IHC expression categories
      (low IHC=11,255; medium IHC=11,070; high IHC=11,023; P=0.98). Mean PTEN
      expression by AQUA was higher in the medium and high IHC categories (low
      IHC=1229; medium IHC=2715; high IHC=2940; P=0.064). Only 2 samples expressed EGFR
      by standard IHC. Mass spectrometry trended toward correlation with standard IHC
      but did not yield interpretable results in the majority of samples. This study
      demonstrates that the relative quantification of signaling protein expression in
      EWS is dependent on the methodology used. Optimization and validation of these
      tools are necessary before clinical application for risk stratification of
      patients or measurement of biomarker expression. 

PMID- 24590123
TI  - Multiplex detection of nucleic acids using a low cost microfluidic chip and a
      personal glucose meter at the point-of-care.
AB  - A simple assay for multiplex DNA detection has been developed using a
      microfluidic chip and a personal glucose meter. By using this system, multiplex
      detection of three genotypes of hepatitis B virus DNA was possible with a
      detection limit of 10 pM. This point-of-care assay represented a versatile
      platform for sensitive multiplex target detection. 

PMID- 24590120
TI  - Thirty-day prevalence of DSM-IV mental disorders among nondeployed soldiers in
      the US Army: results from the Army Study to Assess Risk and Resilience in
      Servicemembers (Army STARRS).
AB  - IMPORTANCE: Although high rates of current mental disorder are known to exist in
      the US Army, little is known about the proportions of these disorders that had
      onsets prior to enlistment. OBJECTIVE: To estimate the proportions of 30-day DSM
      IV mental disorders among nondeployed US Army personnel with first onsets prior
      to enlistment and the extent which role impairments associated with 30-day
      disorders differ depending on whether the disorders had pre- vs post-enlistment
      onsets. DESIGN, SETTING, AND PARTICIPANTS: A representative sample of 5428
      soldiers participating in the Army Study to Assess Risk and Resilience in
      Servicemembers completed self-administered questionnaires and consented to
      linkage of questionnaire responses with administrative records. MAIN OUTCOMES AND
      MEASURES: Thirty-day DSM-IV internalizing (major depressive, bipolar, generalized
      anxiety, panic, and posttraumatic stress) and externalizing (attention
      deficit/hyperactivity, intermittent explosive, alcohol/drug) disorders were
      assessed with validated self-report scales. Age at onset was assessed
      retrospectively. Role impairment was assessed with a modified Sheehan Disability
      Scale. RESULTS: A total of 25.1% of respondents met criteria for any 30-day
      disorder (15.0% internalizing; 18.4% externalizing) and 11.1% for multiple
      disorders. A total of 76.6% of cases reported pre-enlistment age at onset of at
      least one 30-day disorder (49.6% internalizing; 81.7% externalizing). Also, 12.8%
      of respondents reported severe role impairment. Controlling for sociodemographic
      and Army career correlates, which were broadly consistent with other studies, 30
      day disorders with pre-enlistment (chi82 = 131.8, P < .001) and post-enlistment
      (chi72 = 123.8, P < .001) ages at onset both significantly predicted severe role
      impairment, although pre-enlistment disorders were more consistent powerful
      predictors (7 of 8 disorders significant; odds ratios, 1.6-11.4) than post
      enlistment disorders (5 of 7 disorders significant; odds ratios, 1.5-7.7).
      Population-attributable risk proportions of severe role impairment were 21.7% for
      pre-enlistment disorders, 24.3% for post-enlistment disorders, and 43.4% for all
      disorders. CONCLUSIONS AND RELEVANCE: Interventions to limit accession or
      increase resilience of new soldiers with pre-enlistment mental disorders might
      reduce prevalence and impairments of mental disorders in the US Army.

PMID- 24590124
TI  - Plasmon-enhanced photocatalytic water purification.
AB  - Increasing water demand and water scarcity around the world requires the
      development of robust and efficient methods for water purification in the coming
      decades. Here, we report a photocatalytic water purification method using visible
      light (532 nm) utilizing 5 nm gold nanoparticles and their enhancement when
      attached on the surface of silica nanospheres as an inactive support to prevent
      nanoparticle coalescence or sintering. This is a non-toxic, low-cost, and easy
      photocatalytic process which provides high decomposition rates. Decomposition of
      the methyl orange dye is tested as a reaction model and trichloroethylene is
      selected as an example of a real water pollutant. When irradiated at their
      plasmon resonant frequency, the gold nanoparticles generate hydroxyl radicals
      that degradate organic pollutants into non-toxic molecules representing a basic
      mechanism of photocatalytic water purification. 

PMID- 24590125
TI  - A fluorescent aptasensor based on DNA-scaffolded silver-nanocluster for
      ochratoxin A detection.
AB  - The selective detection of ultratrace amounts of ochratoxin A (OTA) is extremely
      important for food safety since it is one of the most toxic and widespread
      mycotoxin. Here we develop a signal-on fluorescent biosensor for detection of OTA
      based on fluorescent DNA-scaffolded silver-nanocluster (AgNCs), structure
      switching of anti-OTA aptamer (Ap) and magnetic beads (MBs), and demonstrate its
      feasibility in the application of detecting OTA in real samples of wheat. The
      method exhibits superior sensitivity with a detection limit as low as 2 pg/mL OTA
      with high specificity. To the best of our knowledge, this is the first attempt to
      detect OTA based on DNA-scaffolded AgNCs, which possesses relatively high
      fluorescence quantum yield and photostability with regard to traditional organic
      dyes and quantum dots. Moreover, combined with the merits of MBs and aptamer, the
      proposed sensor has many advantages such as fabrication easiness, operation
      convenience, low cost, and being fast and portable, which may represent a
      promising path toward routine OTA control.

PMID- 24590126
TI  - An overview of poly(lactic-co-glycolic) acid (PLGA)-based biomaterials for bone
      tissue engineering.
AB  - Poly(lactic-co-glycolic) acid (PLGA) has attracted considerable interest as a
      base material for biomedical applications due to its: (i) biocompatibility; (ii)
      tailored biodegradation rate (depending on the molecular weight and copolymer
      ratio); (iii) approval for clinical use in humans by the U.S. Food and Drug
      Administration (FDA); (iv) potential to modify surface properties to provide
      better interaction with biological materials; and (v) suitability for export to
      countries and cultures where implantation of animal-derived products is
      unpopular. This paper critically reviews the scientific challenge of
      manufacturing PLGA-based materials with suitable properties and shapes for
      specific biomedical applications, with special emphasis on bone tissue
      engineering. The analysis of the state of the art in the field reveals the
      presence of current innovative techniques for scaffolds and material
      manufacturing that are currently opening the way to prepare biomimetic PLGA
      substrates able to modulate cell interaction for improved substitution,
      restoration, or enhancement of bone tissue function. 

PMID- 24590127
TI  - A proteomic approach of bradyrhizobium/aeschynomene root and stem symbioses
      reveals the importance of the fixA locus for symbiosis.
AB  - Rhizobia are soil bacteria that are able to form symbiosis with plant hosts of
      the legume family. These associations result in the formation of organs, called
      nodules in which bacteria fix atmospheric nitrogen to the benefit of the plant.
      Most of our knowledge on the metabolism and the physiology of the bacteria during
      symbiosis derives from studying roots nodules of terrestrial plants. Here we used
      a proteomics approach to investigate the bacterial physiology of photosynthetic
      Bradyrhizobium sp. ORS278 during the symbiotic process with the semi aquatical
      plant Aeschynomene indica that forms root and stem nodules. We analyzed the
      proteomes of bacteria extracted from each type of nodule. First, we analyzed the
      bacteroid proteome at two different time points and found only minor variation
      between the bacterial proteomes of 2-week- and 3-week-old nodules. High
      conservation of the bacteroid proteome was also found when comparing stem nodules
      and root nodules. Among the stem nodule specific proteins were those related to
      the phototrophic ability of Bradyrhizobium sp. ORS278. Furthermore, we compared
      our data with those obtained during an extensive genetic screen previously
      published. The symbiotic role of four candidate genes which corresponding
      proteins were found massively produced in the nodules but not identified during
      this screening was examined. Mutant analysis suggested that in addition to the
      EtfAB system, the fixA locus is required for symbiotic efficiency. 

PMID- 24590129
TI  - Multilineage potential research of bovine amniotic fluid mesenchymal stem cells.
AB  - The use of amnion and amniotic fluid (AF) are abundant sources of mesenchymal
      stem cells (MSCs) that can be harvested at low cost and do not pose ethical
      conflicts. In human and veterinary research, stem cells derived from these
      tissues are promising candidates for disease treatment, specifically for their
      plasticity, their reduced immunogenicity, and high anti-inflammatory potential.
      This work aimed to obtain and characterize bovine amniotic fluid mesenchymal stem
      cells (AFMSC). The bovine AF from the amniotic cavity of pregnant gilts in the
      early stages of gestation (3- and 4-m-old bovine embryos) was collected. AFMSCs
      exhibit a fibroblastic-like morphology only starting from the fourth passage,
      being heterogeneous during the primary culture. Immunofluorescence results showed
      that AFMSCs were positive for beta-integrin, CD44, CD73 and CD166, but negative
      for CD34, CD45. Meanwhile, AFMSCs expressed ES cell markers, such as Oct4, and
      when appropriately induced, are capable of differentiating into ectodermal and
      mesodermal lineages. This study reinforces the emerging importance of these cells
      as ideal tools in veterinary medicine; future studies aimed at a deeper
      evaluation of their immunological properties will allow a better understanding of
      their role in cellular therapy. 

PMID- 24590128
TI  - Nanotoxicity overview: nano-threat to susceptible populations.
AB  - Due to the increasing applications of nanomaterials and nanotechnology, potential
      danger of nanoparticle exposure has become a critical issue. However, recent
      nanotoxicity studies have mainly focused on the health risks to healthy adult
      population. The nanotoxicity effects on susceptible populations (such as
      pregnant, neonate, diseased, and aged populations) have been overlooked. Due to
      the alterations in physiological structures and functions in susceptible
      populations, they often suffer more damage from the same exposure. Thus, it is
      urgent to understand the effects of nanoparticle exposure on these populations.
      In order to fill this gap, the potential effects of nanoparticles to pregnant
      females, neonate, diseased, and aged population, as well as the possible
      underlying mechanisms are reviewed in this article. Investigations show that
      responses from susceptible population to nanoparticle exposure are often more
      severe. Reduced protection mechanism, compromised immunity, and impaired self
      repair ability in these susceptible populations may contribute to the aggravated
      toxicity effects. This review will help minimize adverse effects of nanoparticles
      to susceptible population in future nanotechnology applications. 

PMID- 24590130
TI  - Exposure to diflubenzuron results in an up-regulation of a chitin synthase 1 gene
      in citrus red mite, Panonychus citri (Acari: Tetranychidae).
AB  - Chitin synthase synthesizes chitin, which is critical for the arthropod
      exoskeleton. In this study, we cloned the cDNA sequences of a chitin synthase 1
      gene, PcCHS1, in the citrus red mite, Panonychus citri (McGregor), which is one
      of the most economically important pests of citrus worldwide. The full-length
      cDNA of PcCHS1 contains an open reading frame of 4605 bp of nucleotides, which
      encodes a protein of 1535 amino acid residues with a predicted molecular mass of
      175.0 kDa. A phylogenetic analysis showed that PcCHS1 was most closely related to
      CHS1 from Tetranychus urticae. During P. citri development, PcCHS1 was constantly
      expressed in all stages but highly expressed in the egg stage (114.8-fold higher
      than in the adult). When larvae were exposed to diflubenzuron (DFB) for 6 h, the
      mite had a significantly high mortality rate, and the mRNA expression levels of
      PcCHS1 were significantly enhanced. These results indicate a promising use of DFB
      to control P. citri, by possibly acting as an inhibitor in chitin synthesis as
      indicated by the up-regulation of PcCHS1 after exposure to DFB. 

PMID- 24590131
TI  - Melanoma: smart therapeutic strategies in immuno-oncology.

PMID- 24590132
TI  - Immunotherapy: killing with natural killers, naturally.

PMID- 24590133
TI  - Imaging: reducing ionizing radiation in children and adolescents.

PMID- 24590137
TI  - Rare adverse effect of treatment with minocycline. Minocycline-induced cutaneous
      polyarteritis nodosa.

PMID- 24590138
TI  - Reducing neonatal mortality: are high-coverage women's participatory groups the
      cost-effective solution we have been searching for?

PMID- 24590139
TI  - Reducing neonatal mortality-reply.

PMID- 24590140
TI  - Circumcision is a religious/cultural procedure, not a medical procedure.

PMID- 24590141
TI  - Circumcision is a religious/cultural procedure, not a medical procedure-reply.

PMID- 24590142
TI  - Celiac disease in children and adolescents.

PMID- 24590143
TI  - Complexity analysis of beat-to-beat skin-surface laser-Doppler signals in
      diabetic subjects.
AB  - MOTIVATIONS: This study performed skin-surface laser-Doppler flowmetry (LDF)
      measurements with the aim of verifying if complexity analysis applied to the beat
      to-beat LDF waveform index can be used to discriminate diabetic, prediabetic, and
      normoglycemic subjects. METHODS: Sixty-six subjects were assigned to three age
      matched groups according to the results of oral glucose tolerance tests. Beat-to
      beat analysis was performed on the pulsatile LDF waveform to obtain the pulse-to
      mean ratio (AD) and pulse width (PW), and then approximate-entropy (ApEn) values
      for their 20-minute index sequences were calculated to evaluate the signal
      complexity. RESULTS: AD and PW did not differ significantly among the three study
      groups. ApEn values of AD and PW were significantly larger and marginally larger,
      respectively, in the diabetic group than in the prediabetic and normoglycemic
      groups. CONCLUSION: These results indicate the presence of significant
      differences in ApEn indexes among diabetic, prediabetic, and normoglycemic
      subjects. The presence of increased complexity in the LDF index sequence may be
      partly attributed to the adaptability of the microcirculatory regulatory
      activities or the impairment of the homeostasis mechanism of microcirculatory
      blood-flow perfusion. The present findings may be pertinent to the early
      detection of the diabetes-induced impairment of this perfusion.

PMID- 24590144
TI  - A meta-analysis of reference markers of bone turnover for prediction of fracture.
AB  - The aim of this report was to summarize the clinical performance of two reference
      bone turnover markers (BTMs) in the prediction of fracture risk. We used an
      updated systematic review to examine the performance characteristics of serum
      procollagen type I N propeptide (s-PINP) and serum C-terminal cross-linking
      telopeptide of type I collagen (s-CTX) in fracture risk prediction in untreated
      individuals in prospective cohort studies. We excluded cross-sectional studies.
      Ten potentially eligible publications were identified and six included in the
      meta-analysis. There was a significant association between s-PINP and the risk of
      fracture. The hazard ratio per SD increase in s-PINP (gradient of risk [GR]) was
      1.23 (95 % CI 1.09-1.39) for men and women combined unadjusted for bone mineral
      density. There was also a significant association between s-CTX and risk of
      fracture, GR = 1.18 (95 % CI 1.05-1.34) unadjusted for bone mineral density. For
      the outcome of hip fracture, the association between s-CTX and risk of fracture
      was slightly higher, 1.23 (95 % CI 1.04-1.47). Thus, there is a modest but
      significant association between BTMs and risk of future fractures.

PMID- 24590146
TI  - Laser method for intraoperative evaluation of lower extremity alignment:
      comparison of a novel technique to CT and a conventional method.
AB  - INTRODUCTION: Accurate restoration of mechanical alignment is an important factor
      in reconstructive surgery of the lower extremity. Conventional intraoperative
      methods, such as using an electrocautery cable, provide only a momentary
      evaluation of alignment. In this study, we evaluated a novel technique using a
      laser emitter, which projected the mechanical axis of the lower extremity,
      providing continuous intraoperative information on alignment. MATERIALS AND
      METHODS: Alignment of 16 cadaver lower extremities was measured using the
      electrocautery cable method, the laser method, and CT scan as the standard
      measurement. The mechanical axis was defined by a line from the center of the
      femoral head to the center of the ankle. For simplifying measurements the
      intersection with the tibial plateau was divided into percentages from the medial
      border (0 %) to the lateral border (100 %). For using the laser method a laser
      emitting and laser catching device was developed, which is positioned and
      centered on the femoral head and the ankle using an image intensifier. By
      catching the laser on the knee region the actual mechanical axis is marked.
      RESULTS: The data demonstrated good correlation of the laser method when compared
      to the cable method (P = 0.44). Comparison of the average mechanical axis between
      cable method and CT (P = 0.819) and laser method and CT (P = 0.647) did not show
      a statistically significant difference. Average radiation time in comparison
      between cable method and laser method showed a statistically significant
      difference (P = 0.013), with the laser method requiring more radiation time.
      CONCLUSION: Determination of the mechanical axis during surgery remains a
      difficult clinical problem. Restoration of alignment is an important prognostic
      factor for surgical outcome. Based on these data, the laser method represents a
      simple, yet effective tool for continuous intraoperative evaluation of lower
      extremity alignment.

PMID- 24590147
TI  - The clinical reasoning that guides therapists in interpreting errors in real
      world performance.
AB  - OBJECTIVES: The objective of this study was to examine the reasoning used by
      clinicians when deciding whether errors observed during the performance of
      everyday activities were made by clients with acquired brain injury (ABI) or by
      healthy controls. METHODS: Ninety clinicians observed 27 short video clips of
      subjects (ABI, healthy controls), carrying out the Baycrest Multiple Errands
      Test. On the basis of their observations, they classified subjects into either an
      ABI or healthy control group and specified their reasons. Their reasoning was
      analyzed using qualitative content analysis. RESULTS: The majority of the coded
      material explaining the reasoning behind correct attributions of performance
      errors to people with ABI related to 3 general themes: (1) inefficient executive
      functioning, (2) task-related difficulty, and (3) prediction of impact on
      independence in everyday activities. Clinicians were most successful at
      identifying neurological subjects when subjects either omitted tasks or took an
      excessive amount of time to complete the test. CONCLUSIONS: Correctly
      interpreting performance errors in real-world tests relies on clinicians'
      observational and clinical reasoning skills combined with their theoretical
      knowledge of constructs underlying the evaluation. Some clinical signs bear more
      weight than others when clinicians interpret performance errors to determine
      whether the behavior is pathological.

PMID- 24590145
TI  - Novel insights into the development and maintenance of the blood-brain barrier.
AB  - The blood-brain barrier (BBB) is essential for maintaining homeostasis within the
      central nervous system (CNS) and is a prerequisite for proper neuronal function.
      The BBB is localized to microvascular endothelial cells that strictly control the
      passage of metabolites into and out of the CNS. Complex and continuous tight
      junctions and lack of fenestrae combined with low pinocytotic activity make the
      BBB endothelium a tight barrier for water soluble moleucles. In combination with
      its expression of specific enzymes and transport molecules, the BBB endothelium
      is unique and distinguishable from all other endothelial cells in the body.
      During embryonic development, the CNS is vascularized by angiogenic sprouting
      from vascular networks originating outside of the CNS in a precise spatio
      temporal manner. The particular barrier characteristics of BBB endothelial cells
      are induced during CNS angiogenesis by cross-talk with cellular and acellular
      elements within the developing CNS. In this review, we summarize the currently
      known cellular and molecular mechanisms mediating brain angiogenesis and
      introduce more recently discovered CNS-specific pathways (Wnt/beta-catenin,
      Norrin/Frizzled4 and hedgehog) and molecules (GPR124) that are crucial in BBB
      differentiation and maturation. Finally, based on observations that BBB
      dysfunction is associated with many human diseases such as multiple sclerosis,
      stroke and brain tumors, we discuss recent insights into the molecular mechanisms
      involved in maintaining barrier characteristics in the mature BBB endothelium. 

PMID- 24590148
TI  - Elevated movement path tortuosity in voluntary outdoor ambulation in community
      dwelling veterans with a history of traumatic brain injury.
AB  - OBJECTIVE: In comparison to veterans without a history of traumatic brain injury
      (TBI), we hypothesized that veterans with past TBI would have slower walking
      speed and more path tortuosity, TBI symptoms, problems with spatial orientation,
      and poorer executive function. SETTING: Community nonclinical. PARTICIPANTS:
      Seventeen males (mean age of 37.2 years) reporting prior TBI and 20 non-TBI (mean
      age of 42.9 years). The number of years separating date of discharge and testing
      was 10.8 and 15.4 for the TBI and non-TBI groups, respectively. DESIGN: Small 2
      groups without random assignment. MAIN MEASURES: Brief Traumatic Brain Injury
      Screen, Trail Making Test-B, Clock Drawing Test, walking speed, and distance and
      path tortuosity in 30 minutes of voluntary outdoor walking wearing a small Global
      Positioning Systems recorder. RESULTS: Those with TBI reported 4 Brief Traumatic
      Brain Injury Screen symptoms versus 0.4 for controls (F = 49.1; df = 1,35; P <
      .001) but did not differ on Trail Making Test-B or the Clock Drawing Test.
      Veterans with TBI walked shorter distances, 2.33 km versus 2.84 km (F = 4.8; df =
      1,35; P < .05), and had greater path tortuosity (fractal D of 1.22 vs 1.15; F =
      3.5; df = 1,35; P < .05) but did not differ on travel speed or time spent
      walking. CONCLUSIONS: Traumatic brain injury has persistent symptomatic effects
      and significantly affects ambulation and spatial orientation years after the
      event. These findings corroborate and extend observations linking cognitive
      impairment and ambulation.

PMID- 24590149
TI  - The experience, expression, and control of anger following traumatic brain injury
      in a military sample.
AB  - OBJECTIVE: To investigate the impact of traumatic brain injury (TBI) on the
      experience and expression of anger in a military sample. PARTICIPANTS: A total of
      661 military personnel with a history of TBI and 1204 military personnel with no
      history of TBI. DESIGN: Cross-sectional, between-group design, using multivariate
      analysis of variance. MAIN MEASURE: State-Trait Anger Expression Inventory-2
      (STAXI-2). RESULTS: Participants with a history of TBI had higher scores on the
      STAXI-2 than controls and were 2 to 3 times more likely than the participants in
      the control group to have at least 1 clinically significant elevation on the
      STAXI-2. Results suggested that greater time since injury (ie, months between TBI
      and assessment) was associated with lower scores on the STAXI-2 State Anger
      scale. CONCLUSION: Although the results do not take into account confounding
      psychiatric conditions and cannot address causality, they suggest that a history
      of TBI increases the risk of problems with the experience, expression, and
      control of anger. This bolsters the need for proper assessment of anger when
      evaluating TBI in a military cohort.

PMID- 24590150
TI  - Emergence to the conscious state during inpatient rehabilitation after traumatic
      brain injury in children and young adults: a case series.
AB  - OBJECTIVE: To describe clinical patterns related to emergence to the conscious
      state (CS) in children and young adults with traumatic brain injury receiving
      acute inpatient rehabilitation. SETTING: One academically affiliated pediatric
      brain injury rehabilitation unit. PARTICIPANTS: Fourteen consecutive patients
      aged 1 to 20 years with traumatic brain injury and disorders of consciousness.
      DESIGN: Retrospective case series. MAIN MEASURES: The primary outcome was
      emergence to CS during the inpatient rehabilitation admission. Factors evaluated
      for relationship to emergence to CS included age at injury, admission level of
      consciousness, admission Rappaport Coma/Near-Coma Scale score, and admission
      Cognitive and Linguistic Scale responsiveness item score. RESULTS: Ten of 14
      patients emerged to CS during the inpatient rehabilitation admission. Those who
      emerged to CS had higher levels of responsiveness at admission to rehabilitation.
      There was a trend toward older age in those who emerged to CS. CONCLUSIONS: In
      this limited cohort, the majority of patients with disorders of consciousness
      after traumatic brain injury emerged to CS during acute inpatient rehabilitation,
      underscoring the presence of functional goals for inpatient rehabilitation in
      this population. Larger cohorts are needed to further explore clinical variables
      associated with emergence to CS.

PMID- 24590151
TI  - Measures of injury severity and prediction of acute traumatic brain injury
      outcomes.
AB  - OBJECTIVE: To examine the comparative efficacy of 3 common measures of traumatic
      brain injury (TBI) severity for predicting inpatient outcomes upon hospital
      discharge. SETTING: Acute brain injury rehabilitation unit at level 1 trauma
      center. PARTICIPANTS: 100 patients with TBI. DESIGN: Retrospective analysis of
      injury severity, demographic, and outcome data. MAIN MEASURES: Glasgow Coma Scale
      (GCS) at admission, time to follow commands (TTC), duration of posttraumatic
      amnesia (PTA), and Functional Independence Measure at hospital discharge.
      RESULTS: A hierarchal multiple regression revealed that duration of PTA was a
      significant and powerful unique predictor of Functional Independence Measure
      scores at discharge (beta = -0.46, P = .001), while TTC (beta = 0.26, P = .056)
      and GCS (beta = 0.16, P = .143) were not. These effects were present even after
      controlling for age, gender, educational level, racial/ethnic minority status,
      cause of injury, history of substance abuse, and neurosurgical intervention.
      CONCLUSION: Although clinicians often use GCS scores and TTC when assessing acute
      TBI severity and during treatment formulation, this study provides evidence that
      duration of PTA may be a more meaningful predictor of patients' functional levels
      at discharge.

PMID- 24590152
TI  - Exploring minor hockey players' knowledge and attitudes toward concussion:
      implications for prevention.
AB  - OBJECTIVE: To evaluate minor hockey players' attitudes and knowledge about sport
      concussions. PARTICIPANTS: Male and female Pee Wee, Bantam, and Midget level
      players (n = 183) participating in minor hockey and a comparison group of non
      hockey players (n = 57). DESIGN: Survey. MAIN MEASURES: Player knowledge and
      attitudes were evaluated with a standardized questionnaire developed for the
      purpose of this study. Descriptive statistics including cross-tabulations and
      proportion comparisons were used to report the data. RESULTS: Players had
      foundational knowledge about concussions; however, more than half underestimated
      the prevalence and more than 30% were unaware of return to play protocols.
      Although nearly all players knew what they "should" do when concussed, 33% did
      not follow recommendations. Players reported more concern and appreciation of the
      seriousness of concussion than non-players, but they tended to minimize their
      vulnerability. The most common and helpful information sources were parents,
      doctors, and coaches, and therefore knowledge translation efforts should target
      theses audiences. CONCLUSION: Young athletes continue to demonstrate gaps in
      their knowledge of concussions. In addition, attitudes toward concussion suggest
      a developmental trajectory with younger athletes being most likely to ignore
      current recommended guidelines.

PMID- 24590153
TI  - Racial/ethnic and insurance status disparities in discharge to
      posthospitalization care for patients with traumatic brain injury.
AB  - OBJECTIVES: Professional, posthospitalization care (PHC) can improve outcomes
      among patients with traumatic brain injury. We examined disparities in discharge
      to PHC by patients' race/ethnicity and insurance type. PARTICIPANTS: A total of
      6061 adults hospitalized for unintentional traumatic brain injury in Oregon, 2008
      to 2011. MAIN OUTCOME MEASURE: Posthospitalization care was assessed on the basis
      of discharge disposition. Multivariable logistic regression was used to estimate
      effects of race/ethnicity and insurance on referral to PHC while controlling for
      potential confounders. Generalized estimating equations were used to calculate
      odds ratios (ORs) and 95% confidence intervals (CIs), accounting for clustering
      of data by hospital. RESULTS: 28% of patients were discharged to PHC. While
      controlling for potential confounders, Hispanics were less likely to be
      discharged to PHC (OR, 0.62; CI, 0.40-0.96) than non-Hispanic whites. Compared
      with patients with private insurance, uninsured patients were less likely to be
      discharged to PHC (OR, 0.19; CI, 0.11-0.32) whereas patients with public
      insurance (OR, 1.65; CI, 1.33-2.05) and worker's compensation (OR, 1.66; CI, 1.09
      2.52) were more likely to be discharged to PHC. CONCLUSIONS: Results suggest that
      racial/ethnic and insurance disparities exist in discharge to postacute care
      after hospitalization for traumatic brain injury. Future research should examine
      factors that might contribute to and reduce these inequities in care.

PMID- 24590154
TI  - Incidence of severe dysphagia after brain surgery in pediatric traumatic brain
      injury: a nationwide population-based retrospective study.
AB  - OBJECTIVES: To investigate the incidence of dysphagia and medical resource
      utilization in a nationwide population of pediatric patients with traumatic brain
      injury (TBI). SETTING: Subjects' data were obtained from the Taiwan National
      Health Insurance Research Database. PARTICIPANTS: Between 2000 and 2008, 6290
      children less than 18 years old who had received surgery post-TBI were included
      in the study. DESIGN: Retrospective study. MAIN OUTCOME MEASURE: Biographic data
      and medical utilization results. RESULTS: Of all the children postsurgery after
      TBI, 12.3% were categorized as having severe dysphagia. The occurrence of severe
      dysphagia was not related to sex but was statistically and significantly related
      to a younger mean age. The relationship between age and dysphagia also showed an
      interestingly biphasic distribution, mostly in the subgroups of 1 to 3 and 16 to
      18 years of age. The medical resource utilization was higher in severely
      dysphagia patients, but only 8.4% received intervention by a speech language
      pathologist. CONCLUSIONS: Severe dysphagia among postsurgical pediatric patients
      after TBI is relatively common, and those with severe dysphagia have a greater
      need for medical services. However, the ratio of such patients who receive
      swallowing treatment is still low in Taiwan. Clinicians are prompted to pay more
      attention to the impairment in functional oral intake of children postsurgery
      after TBI.

PMID- 24590155
TI  - Acute inflammatory biomarker profiles predict depression risk following moderate
      to severe traumatic brain injury.
AB  - OBJECTIVE: To examine whether acute inflammation profiles predict posttraumatic
      depression (PTD) risk 6 and 12 months after traumatic brain injury. SETTING:
      University-affiliated level 1 trauma center and community. PARTICIPANTS: Adults
      with moderate to severe traumatic brain injury (acute serum levels: n = 50; acute
      cerebrospinal fluid (CSF) levels: n = 41). DESIGN: Prospective cohort study. MAIN
      MEASURES: Patient Health Questionnaire; inflammatory biomarkers (interleukin [IL]
      1beta, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, tumor necrosis factor alpha,
      soluble vascular adhesion molecule [sVCAM-1], soluble intracellular adhesion
      molecule [sICAM-1], soluble Fas [sFAS]). RESULTS: Higher levels of acute CSF
      cytokine surface markers (sVCAM-1, sICAM-1, and sFAS) in an inflammatory
      biomarker risk (IBR) score were associated with a 3.920-fold increase in the odds
      of developing PTD at 6 months (95% confidence interval: 1.163-8.672). Having
      sICAM-1, sVCAM-1, or sFAS above the 75th percentile had a positive predictive
      value of 85.7% for PTD risk at 6 months. An IBR score including inflammatory
      biomarkers IL-7 and IL-8 showed a trending association with 12-month PTD risk
      (odds ratio = 3.166, 95% confidence interval: 0.936-10.708). CONCLUSION: Acute
      CSF IBR scores show promise for identifying individuals at risk for PTD. Further
      research should assess acute CSF inflammatory biomarkers' relationships to
      chronic inflammation as a mechanism of PTD and should explore anti-inflammatory
      treatments for PTD, as well as prevention and screening protocols, and link
      inflammatory biomarkers to symptom tracking.

PMID- 24590157
TI  - Cyclization reactions of bis(allenes) for the synthesis of
      polycarbo(hetero)cycles.
AB  - The chemistry of allenes is an appealing topic which fascinates chemists
      nowadays. Their reactivity and versatility makes this skeleton a useful moiety to
      create a great variety of structures depending on the functional groups attached
      and the reaction conditions used. Recently, there is a growing interest in the
      study of the reactivity of bis(allenes) inspired in the chemistry developed in
      simple allenes. In this review a collection of examples of cyclization reactions
      of bis(allenes) is presented as well as the future perspectives. 

PMID- 24590156
TI  - White matter compromise in veterans exposed to primary blast forces.
AB  - OBJECTIVE: Use diffusion tensor imaging to investigate white matter alterations
      associated with blast exposure with or without acute symptoms of traumatic brain
      injury (TBI). PARTICIPANTS: Forty-five veterans of the recent military conflicts
      included 23 exposed to primary blast without TBI symptoms, 6 having primary blast
      with mild TBI, and 16 unexposed to blast. DESIGN: Cross-sectional case-control
      study. MAIN MEASURES: Neuropsychological testing and diffusion tensor imaging
      metrics that quantified the number of voxel clusters with altered fractional
      anisotropy (FA) radial diffusivity, and axial diffusivity, regardless of their
      spatial location. RESULTS: Significantly lower FA and higher radial diffusivity
      were observed in veterans exposed to primary blast with and without mild TBI
      relative to blast-unexposed veterans. Voxel clusters of lower FA were spatially
      dispersed and heterogeneous across affected individuals. CONCLUSION: These
      results suggest that lack of clear TBI symptoms following primary blast exposure
      may not accurately reflect the extent of brain injury. If confirmed, our findings
      would argue for supplementing the established approach of making diagnoses based
      purely on clinical history and observable acute symptoms with novel neuroimaging
      based diagnostic criteria that "look below the surface" for pathology.

PMID- 24590158
TI  - Gelatine methacrylamide-based hydrogels: an alternative three-dimensional cancer
      cell culture system.
AB  - Modern cancer research requires physiological, three-dimensional (3-D) cell
      culture platforms, wherein the physical and chemical characteristics of the
      extracellular matrix (ECM) can be modified. In this study, gelatine
      methacrylamide (GelMA)-based hydrogels were characterized and established as in
      vitro and in vivo spheroid-based models for ovarian cancer, reflecting the
      advanced disease stage of patients, with accumulation of multicellular spheroids
      in the tumour fluid (ascites). Polymer concentration (2.5-7% w/v) strongly
      influenced hydrogel stiffness (0.5+/-0.2kPa to 9.0+/-1.8kPa) but had little
      effect on solute diffusion. The diffusion coefficient of 70kDa fluorescein
      isothiocyanate (FITC)-labelled dextran in 7% GelMA-based hydrogels was only 2.3
      times slower compared to water. Hydrogels of medium concentration (5% w/v GelMA)
      and stiffness (3.4kPa) allowed spheroid formation and high proliferation and
      metabolic rates. The inhibition of matrix metalloproteinases and consequently ECM
      degradability reduced spheroid formation and proliferation rates. The
      incorporation of the ECM components laminin-411 and hyaluronic acid further
      stimulated spheroid growth within GelMA-based hydrogels. The feasibility of pre
      cultured GelMA-based hydrogels as spheroid carriers within an ovarian cancer
      animal model was proven and led to tumour development and metastasis. These
      tumours were sensitive to treatment with the anti-cancer drug paclitaxel, but not
      the integrin antagonist ATN-161. While paclitaxel and its combination with ATN
      161 resulted in a treatment response of 33-37.8%, ATN-161 alone had no effect on
      tumour growth and peritoneal spread. The semi-synthetic biomaterial GelMA
      combines relevant natural cues with tunable properties, providing an alternative,
      bioengineered 3-D cancer cell culture in in vitro and in vivo model systems.

PMID- 24590159
TI  - Topologically defined composites of collagen types I and V as in vitro cell
      culture scaffolds.
AB  - Cell fate is known to be triggered by cues from the extracellular matrix,
      including its chemical, biological and physical characteristics. Specifically,
      mechanical and topological properties are increasingly recognized as important
      signals. The aim of this work was to provide an easily accessible biomimetic in
      vitro platform of topologically defined collagen I matrices to dissect cell
      behaviour under various conditions in vitro. We reconstituted covalently bound
      layers of three-dimensional (3-D) networks of collagen type I and collagen type V
      with a defined network topology. A new erosion algorithm enabled us to analyse
      the mean pore diameter and fibril content, while the mean fibril diameter was
      examined by an autocorrelation method. Different concentrations and ratios of
      collagen I and V resulted in pore diameters from 2.4 to 4.5MUm and fibril
      diameters from 0.6 to 0.8MUm. A comparison of telopeptide intact collagen I to
      telopeptide deficient collagen I revealed obvious differences in network
      structure. The good correlation of the topological data to measurements of
      network stiffness as well as invasion of human dermal fibroblasts proves that the
      topological analysis provides meaningful measures of the functional
      characteristics of the reconstituted 3-D collagen matrices.

PMID- 24590160
TI  - Covalent attachment of a three-dimensionally printed thermoplast to a gelatin
      hydrogel for mechanically enhanced cartilage constructs.
AB  - Hydrogels can provide a suitable environment for tissue formation by embedded
      cells, which makes them suitable for applications in regenerative medicine.
      However, hydrogels possess only limited mechanical strength, and must therefore
      be reinforced for applications in load-bearing conditions. In most approaches the
      reinforcing component and the hydrogel network have poor interactions and the
      synergetic effect of both materials on the mechanical properties is not
      effective. Therefore, in the present study, a thermoplastic polymer blend of
      poly(hydroxymethylglycolide-co-epsilon-caprolactone)/poly(epsilon-caprolactone)
      (pHMGCL/PCL) was functionalized with methacrylate groups (pMHMGCL/PCL) and
      covalently grafted to gelatin methacrylamide (gelMA) hydrogel through
      photopolymerization. The grafting resulted in an at least fivefold increase in
      interface-binding strength between the hydrogel and the thermoplastic polymer
      material. GelMA constructs were reinforced with three-dimensionally printed
      pHMGCL/PCL and pMHMGCL/PCL scaffolds and tested in a model for a focal articular
      cartilage defect. In this model, covalent bonds at the interface of the two
      materials resulted in constructs with an improved resistance to repeated axial
      and rotational forces. Moreover, chondrocytes embedded within the constructs were
      able to form cartilage-specific matrix both in vitro and in vivo. Thus, by
      grafting the interface of different materials, stronger hybrid cartilage
      constructs can be engineered.

PMID- 24590161
TI  - Surface topography and chemistry shape cellular behavior on wide band-gap
      semiconductors.
AB  - The chemical stability and electrical properties of gallium nitride make it a
      promising material for the development of biocompatible electronics, a range of
      devices including biosensors as well as interfaces for probing and controlling
      cellular growth and signaling. To improve the interface formed between the probe
      material and the cell or biosystem, surface topography and chemistry can be
      applied to modify the ways in which the device interacts with its environment.
      PC12 cells are cultured on as-grown planar, unidirectionally polished, etched
      nanoporous and nanowire GaN surfaces with and without a physisorbed peptide
      sequence that promotes cell adhesion. While cells demonstrate preferential
      adhesion to roughened surfaces over as-grown flat surfaces, the topography of
      that roughness also influences the morphology of cellular adhesion and
      differentiation in neurotypic cells. Addition of the peptide sequence generally
      contributes further to cellular adhesion and promotes development of stereotypic
      long, thin neurite outgrowths over alternate morphologies. The dependence of cell
      behavior on both the topographic morphology and surface chemistry is thus
      demonstrated, providing further evidence for the importance of surface
      modification for modulating bio-inorganic interfaces.

PMID- 24590163
TI  - Storage stability of optimal liposome-polyethylenimine complexes (lipopolyplexes)
      for DNA or siRNA delivery.
AB  - The delivery of nucleic acids such as DNA or siRNA still represents a major
      hurdle, especially with regard to possible therapeutic applications in vivo. Much
      attention has been focused on the development of non-viral gene delivery vectors,
      including liposomes or cationic polymers. Among them, polyethylenimines (PEIs)
      have been widely explored for the delivery of nucleic acids and show promising
      results. The combination of cationic polymers and liposomes (lipopolyplexes) for
      gene delivery may further improve their efficacy and biocompatibility, by
      combining the favourable properties of lipid systems (high stability, efficient
      cellular uptake, low cytotoxicity) and PEIs (nucleic acid condensation,
      facilitated endosomal release). In this study, we systematically analyse various
      conditions for the preparation of liposome-polyethylenimine-based lipopolyplexes
      with regard to biological activity (DNA transfection efficacy, siRNA knockdown
      efficacy) and physicochemical properties (size, zeta potential, stability). This
      includes the exploration of lipopolyplex compositions containing different
      liposomes and different relevant branched or linear low-molecular-weight PEIs. We
      establish optimal parameters for lipopolyplex generation, based on various PEIs,
      N/P ratios, lipids, lipid/PEI ratios and preparation conditions. Importantly, we
      also demonstrate that certain lipopolyplexes retain their biological activity and
      physicochemical integrity upon prolonged storage, even at 37 degrees C and/or in
      the presence of serum, thus providing formulations with considerably higher
      stability as compared to polyplexes. In conclusion, we establish optimal liposome
      polyethylenimine lipopolyplexes that allow storage under ambient conditions. This
      is the basis and an essential prerequisite for novel, promising and easy-to
      handle formulations for possible therapeutic applications.

PMID- 24590164
TI  - Biological control of crystallographic architecture: hierarchy and co-alignment
      parameters.
AB  - Mytilus edulis prismatic calcite and nacre layers exhibit a crystallographic
      structural hierarchy which differs substantially from the morphological
      hierarchy. This makes these biomaterials fundamentally different from classical
      crystalline materials. Morphological building units are defined by their
      surrounding organic matrix membranes, e.g. calcite fibers or nacre tablets. The
      crystallographic building units are defined by crystallographic co-orientation.
      Electron backscatter diffraction quantitatively shows how crystallographic co
      orientation propagates across matrix membranes to form highly co-oriented low
      mosaic composite-crystal grains, i.e. calcite fiber bundles with an internal
      mosaic spread of 0.5 degrees  full width at half maximum (FWHM) or nacre
      towergrains with an internal mosaic spread of 2 degrees  FWHM. These low-mosaic
      composite crystals form much larger composite-crystal supergrains, which exhibit
      a high mosaicity due to misorientations of their constituting calcite fiber
      bundles or nacre towergrains. For the aragonite layer these supergrains nucleate
      in one of three aragonite {110} twin orientations; as a consequence the nacre
      layer exhibits a twin-domain structure, i.e. the boundaries of adjacent
      supergrains exhibit a high probability for misorientations around the aragonite c
      axis with an angle near 63.8 degrees . Within the supergrains, the constituting
      towergrains exhibit a high probability for misorientations around the aragonite a
      axis with a geometric mean misorientation angle of 10.6 degrees . The calcite
      layer is composed of a single composite-crystal supergrain on at least the
      submillimeter length scale. Mutual misorientations of adjacent fiber bundles
      within the calcite supergrain are mainly around the calcite c-axis with a
      geometric mean misorientation angle of 9.4 degrees . The c-axis is not parallel
      to the long axis of the fibers but rather to the (107) plane normal. The
      frequency distribution for the occurrence of misorientation angles within
      supergrains reflects the ability of the organism to maintain homoepitaxial
      crystallization over a certain length scale. This probability density is
      distributed log-normally which can be described by a geometric mean and a
      multiplicative standard deviation. Hence, those parameters are suggested to be a
      numerical measure for the biological control over crystallographic texture. 

PMID- 24590162
TI  - A review on the wettability of dental implant surfaces I: theoretical and
      experimental aspects.
AB  - The surface wettability of biomaterials determines the biological cascade of
      events at the biomaterial/host interface. Wettability is modulated by surface
      characteristics, such as surface chemistry and surface topography. However, the
      design of current implant surfaces focuses mainly on specific micro- and
      nanotopographical features, and is still far from predicting the concomitant
      wetting behavior. There is an increasing interest in understanding the wetting
      mechanisms of implant surfaces and the role of wettability in the biological
      response at the implant/bone or implant/soft tissue interface. Fundamental
      knowledge related to the influence of surface roughness (i.e. a quantification of
      surface topography) on titanium and titanium alloy surface wettability, and the
      different associated wetting regimes, can improve our understanding of the role
      of wettability of rough implant surfaces on the biological outcome. Such an
      approach has been applied to biomaterial surfaces only in a limited way. Focusing
      on titanium dental and orthopaedic implants, the present study reviews the
      current knowledge on the wettability of biomaterial surfaces, encompassing basic
      and applied aspects that include measurement techniques, thermodynamic aspects of
      wetting and models predicting topographical and roughness effects on the wetting
      behavior. 

PMID- 24590165
TI  - The LabTube - a novel microfluidic platform for assay automation in laboratory
      centrifuges.
AB  - Assay automation is the key for successful transformation of modern biotechnology
      into routine workflows. Yet, it requires considerable investment in processing
      devices and auxiliary infrastructure, which is not cost-efficient for
      laboratories with low or medium sample throughput or point-of-care testing. To
      close this gap, we present the LabTube platform, which is based on assay specific
      disposable cartridges for processing in laboratory centrifuges. LabTube
      cartridges comprise interfaces for sample loading and downstream applications and
      fluidic unit operations for release of prestored reagents, mixing, and solid
      phase extraction. Process control is achieved by a centrifugally-actuated ballpen
      mechanism. To demonstrate the workflow and functionality of the LabTube platform,
      we show two LabTube automated sample preparation assays from laboratory routines:
      DNA extractions from whole blood and purification of His-tagged proteins. Equal
      DNA and protein yields were observed compared to manual reference runs, while
      LabTube automation could significantly reduce the hands-on-time to one minute per
      extraction. 

PMID- 24590166
TI  - In-vivo evaluation of tamoxifen-loaded microspheres based on mixtures of poly
      (D,L-lactide-co-glycolide) and poly (D,L-lactide) polymers.
AB  - Microspheres of different proportions of poly-(D,L-lactide-co-glycolide) and poly
      (D,L-lactide) were formulated by spray drying as a drug-delivery system for the
      treatment of breast cancer with tamoxifen. These systems had been evaluated
      previously in vitro and showed very positive results that have led to further
      assessment in vivo. This work evaluates the performance of these systems in an
      organism by carrying out a study in female Wistar rats. Microspheres were
      subcutaneously injected into the back of rats for the assessment of not only the
      biocompatibility but also the release of the drug contained and its
      biodistribution. As, in vitro, these systems could release the drug under
      physiological conditions; different plasma concentrations of tamoxifen and one of
      its metabolites, 4-hydroxy-tamoxifen, were achieved depending on the polymer
      composition. Microspheres could reduce the accumulation of the drug in different
      nontarget organs and presented good biocompatibility. 

PMID- 24590168
TI  - Feroz Papa: Saving cells from themselves.

PMID- 24590167
TI  - PEG-detachable lipid-polymer hybrid nanoparticle for delivery of chemotherapy
      drugs to cancer cells.
AB  - The experiment aimed to increase the drug-delivery efficiency of poly-lactic-co
      glycolic acid (PLGA) nanoparticles. Lipid-polymer hybrid nanoparticles (LPNs-1)
      were prepared using PLGA as a hydrophobic core and FA-PEG-hyd-DSPE as an
      amphiphilic shell. Uniform and spherical nanoparticles with an average size of
      185 nm were obtained using the emulsification solvent evaporation method. The
      results indicated that LPNs-1 showed higher drug loading compared with naked PLGA
      nanoparticles (NNPs). Drug release from LPNs-1 was faster in an acidic
      environment than in a neutral environment. LPNs-1 showed higher cytotoxicity on
      KB cells, A549 cells, MDA-MB-231 cells, and MDA-MB-231/ADR cells compared with
      free doxorubicin (DOX) and NNPs. The results also showed that, compared with free
      DOX and NNPs, LPNs-1 delivered more DOX to the nuclear of KB cells and MDA-MB
      231/ADR cells. LPNs-1 induced apoptosis in KB cells and MDA-MB-231/ADR cells in a
      dose-dependent manner. The above data indicated that DOX-loaded LPNs-1 could kill
      not only normal tumor cells but also drug-resistant tumor cells. These results
      indicated that modification of PLGA nanoparticles with FA-PEG-hyd-DSPE could
      considerably increase the drug-delivery efficiency and LPNs-1 had potential in
      the delivery of chemotherapeutic agents in the treatment of cancer. 

PMID- 24590169
TI  - Protein tagging reveals new insights into signaling in flagella.
AB  - In this issue, Oda et al. (2014. J. Cell Biol.
      http://dx.doi.org/10.1083/jcb.201312014) use mutant analysis, protein tagging,
      and cryoelectron tomography to determine the detailed location of components in
      flagellar radial spokes-a complex of proteins that connect the peripheral
      microtubule doublets to the central pair. Remarkably, this approach revealed an
      interaction between radial spokes and the central pair based on geometry rather
      than a specific signaling mechanism, highlighting the importance of studying a
      system in three dimensions. 

PMID- 24590171
TI  - Preperoxisomal vesicles can form in the absence of Pex3.
AB  - We demonstrate that the peroxin Pex3 is not required for the formation of
      peroxisomal membrane structures in yeast pex3 mutant cells. Notably, pex3 mutant
      cells already contain reticular and vesicular structures that harbor key proteins
      of the peroxisomal receptor docking complex-Pex13 and Pex14-as well as the matrix
      proteins Pex8 and alcohol oxidase. Other peroxisomal membrane proteins in these
      cells are unstable and transiently localized to the cytosol (Pex10, Pmp47) or
      endoplasmic reticulum (Pex11). These reticular and vesicular structures are more
      abundant in cells of a pex3 atg1 double deletion strain, as the absence of Pex3
      may render them susceptible to autophagic degradation, which is blocked in this
      double mutant. Contrary to earlier suggestions, peroxisomes are not formed de
      novo from the endoplasmic reticulum when the PEX3 gene is reintroduced in pex3
      cells. Instead, we find that reintroduced Pex3 sorts to the preperoxisomal
      structures in pex3 cells, after which these structures mature into normal
      peroxisomes. 

PMID- 24590170
TI  - Review: biogenesis of the multifunctional lipid droplet: lipids, proteins, and
      sites.
AB  - Lipid droplets (LDs) are ubiquitous dynamic organelles that store and supply
      lipids in all eukaryotic and some prokaryotic cells for energy metabolism,
      membrane synthesis, and production of essential lipid-derived molecules. Interest
      in the organelle's cell biology has exponentially increased over the last decade
      due to the link between LDs and prevalent human diseases and the discovery of new
      and unexpected functions of LDs. As a result, there has been significant recent
      progress toward understanding where and how LDs are formed, and the specific
      lipid pathways that coordinate LD biogenesis. 

PMID- 24590172
TI  - Mechanisms of HsSAS-6 assembly promoting centriole formation in human cells.
AB  - SAS-6 proteins are thought to impart the ninefold symmetry of centrioles, but the
      mechanisms by which their assembly occurs within cells remain elusive. In this
      paper, we provide evidence that the N-terminal, coiled-coil, and C-terminal
      domains of HsSAS-6 are each required for procentriole formation in human cells.
      Moreover, the coiled coil is necessary and sufficient to mediate HsSAS-6
      centrosomal targeting. High-resolution imaging reveals that GFP-tagged HsSAS-6
      variants localize in a torus around the base of the parental centriole before S
      phase, perhaps indicative of an initial loading platform. Moreover, fluorescence
      recovery after photobleaching analysis demonstrates that HsSAS-6 is immobilized
      progressively at centrosomes during cell cycle progression. Using fluorescence
      correlation spectroscopy and three-dimensional stochastic optical reconstruction
      microscopy, we uncover that HsSAS-6 is present in the cytoplasm primarily as a
      homodimer and that its oligomerization into a ninefold symmetrical ring occurs at
      centrioles. Together, our findings lead us to propose a mechanism whereby HsSAS-6
      homodimers are targeted to centrosomes where the local environment and high
      concentration of HsSAS-6 promote oligomerization, thus initiating procentriole
      formation. 

PMID- 24590173
TI  - CIP2A oncoprotein controls cell growth and autophagy through mTORC1 activation.
AB  - mTORC1 (mammalian target of rapamycin complex 1) integrates information regarding
      availability of nutrients and energy to coordinate protein synthesis and
      autophagy. Using ribonucleic acid interference screens for autophagy-regulating
      phosphatases in human breast cancer cells, we identify CIP2A (cancerous inhibitor
      of PP2A [protein phosphatase 2A]) as a key modulator of mTORC1 and autophagy.
      CIP2A associates with mTORC1 and acts as an allosteric inhibitor of mTORC1
      associated PP2A, thereby enhancing mTORC1-dependent growth signaling and
      inhibiting autophagy. This regulatory circuit is reversed by ubiquitination and
      p62/SQSTM1-dependent autophagic degradation of CIP2A and subsequent inhibition of
      mTORC1 activity. Consistent with CIP2A's reported ability to protect c-Myc
      against proteasome-mediated degradation, autophagic degradation of CIP2A upon
      mTORC1 inhibition leads to destabilization of c-Myc. These data characterize
      CIP2A as a distinct regulator of mTORC1 and reveals mTORC1-dependent control of
      CIP2A degradation as a mechanism that links mTORC1 activity with c-Myc stability
      to coordinate cellular metabolism, growth, and proliferation. 

PMID- 24590174
TI  - Munc18-1 redistributes in nerve terminals in an activity- and PKC-dependent
      manner.
AB  - Munc18-1 is a soluble protein essential for synaptic transmission. To investigate
      the dynamics of endogenous Munc18-1 in neurons, we created a mouse model
      expressing fluorescently tagged Munc18-1 from the endogenous munc18-1 locus. We
      show using fluorescence recovery after photobleaching in hippocampal neurons that
      the majority of Munc18-1 trafficked through axons and targeted to synapses via
      lateral diffusion together with syntaxin-1. Munc18-1 was strongly expressed at
      presynaptic terminals, with individual synapses showing a large variation in
      expression. Axon-synapse exchange rates of Munc18-1 were high: during
      stimulation, Munc18-1 rapidly dispersed from synapses and reclustered within
      minutes. Munc18-1 reclustering was independent of syntaxin-1, but required
      calcium influx and protein kinase C (PKC) activity. Importantly, a PKC
      insensitive Munc18-1 mutant did not recluster. We show that synaptic Munc18-1
      levels correlate with synaptic strength, and that synapses that recruit more
      Munc18-1 after stimulation have a larger releasable vesicle pool. Hence, PKC
      dependent dynamic control of Munc18-1 levels enables individual synapses to tune
      their output during periods of activity. 

PMID- 24590175
TI  - Mechanosignaling between central apparatus and radial spokes controls axonemal
      dynein activity.
AB  - Cilia/flagella are conserved organelles that generate fluid flow in eukaryotes.
      The bending motion of flagella requires concerted activity of dynein motors.
      Although it has been reported that the central pair apparatus (CP) and radial
      spokes (RSs) are important for flagellar motility, the molecular mechanism
      underlying CP- and RS-mediated dynein regulation has not been identified. In this
      paper, we identified nonspecific intermolecular collision between CP and RS as
      one of the regulatory mechanisms for flagellar motility. By combining
      cryoelectron tomography and motility analyses of Chlamydomonas reinhardtii
      flagella, we show that binding of streptavidin to RS heads paralyzed flagella.
      Moreover, the motility defect in a CP projection mutant could be rescued by the
      addition of exogenous protein tags on RS heads. Genetic experiments demonstrated
      that outer dynein arms are the major downstream effectors of CP- and RS-mediated
      regulation of flagellar motility. These results suggest that mechanosignaling
      between CP and RS regulates dynein activity in eukaryotic flagella. 

PMID- 24590177
TI  - A quantum dot in topological insulator nanofilm.
AB  - We introduce a quantum dot in topological insulator nanofilm as a bump at the
      surface of the nanofilm. Such a quantum dot can localize an electron if the size
      of the dot is large enough, ?5 nm. The quantum dot in topological insulator
      nanofilm has states of two types, which belong to two ('conduction' and
      'valence') bands of the topological insulator nanofilm. We study the energy
      spectra of such defined quantum dots. We also consider intraband and interband
      optical transitions within the dot. The optical transitions of the two types have
      the same selection rules. While the interband absorption spectra have multi-peak
      structure, each of the intraband spectra has one strong peak and a few weak high
      frequency satellites. 

PMID- 24590176
TI  - Twist1-induced dissemination preserves epithelial identity and requires E
      cadherin.
AB  - Dissemination of epithelial cells is a critical step in metastatic spread.
      Molecular models of dissemination focus on loss of E-cadherin or repression of
      cell adhesion through an epithelial to mesenchymal transition (EMT). We sought to
      define the minimum molecular events necessary to induce dissemination of cells
      out of primary murine mammary epithelium. Deletion of E-cadherin disrupted
      epithelial architecture and morphogenesis but only rarely resulted in
      dissemination. In contrast, expression of the EMT transcription factor Twist1
      induced rapid dissemination of cytokeratin-positive epithelial cells. Twist1
      induced dramatic transcriptional changes in extracellular compartment and cell
      matrix adhesion genes but not in cell-cell adhesion genes. Surprisingly, we
      observed disseminating cells with membrane-localized E-cadherin and beta-catenin,
      and E-cadherin knockdown strongly inhibited Twist1-induced single cell
      dissemination. Dissemination can therefore occur with retention of epithelial
      cell identity. The spread of cancer cells during metastasis could similarly
      involve activation of an epithelial motility program without requiring a
      transition from epithelial to mesenchymal character. 

PMID- 24590179
TI  - Effect of Ising-type Tb3+ ions on the low-temperature magnetism of La, Ca
      cobaltite.
AB  - Crystal and magnetic structures of the x = 0.2 member of the La0.8-xTbxCa0.2CoO3
      perovskite series have been determined from powder neutron diffraction.
      Enhancement of the diffraction peaks due to ferromagnetic or cluster glass
      ordering is observed below TC = 55 K. The moments first evolve on Co sites, and
      ordering of Ising-type Tb(3+) moments is induced at lower temperatures by a
      molecular field due to Co ions. The final magnetic configuration is collinear Fx
      for the cobalt subsystem, while it is canted FxCy for terbium ions. The rare
      earth moments align along local Ising axes within the ab-plane of the
      orthorhombic Pbnm structure. The behavior in external fields up to 70-90 kOe has
      been probed by magnetization and heat capacity measurements. The dilute terbium
      ions contribute to significant coercivity and remanence that both steeply
      increase with decreasing temperature. A remarkable manifestation of the Tb(3+)
      Ising character is the observation of a low-temperature region with an
      anomalously large linear term of heat capacity and its field dependence. Similar
      behaviors are detected also for other terbium dopings x = 0.1 and 0.3. 

PMID- 24590180
TI  - Generation of spatiotemporal calcium patterns by coupling a pH-oscillator to a
      complexation equilibrium.
AB  - Sustained spatiotemporal pH and calcium patterns are produced in a non
      equilibrium inorganic reaction-diffusion system by coupling two modules, the
      bromate-sulfite-ferrocyanide pH-oscillator and the pH-sensitive complexation of
      Ca(2+) by ethylenediaminetetraacetate. The development of chemical waves is
      mainly determined by the oscillatory module, however, the formation of the
      localised stationary patterns results in the synergistic interaction between the
      modules. 

PMID- 24590178
TI  - Prevalence and correlates of suicidal behavior among soldiers: results from the
      Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS).
AB  - IMPORTANCE: The suicide rate among US Army soldiers has increased substantially
      in recent years. OBJECTIVES: To estimate the lifetime prevalence and
      sociodemographic, Army career, and psychiatric predictors of suicidal behaviors
      among nondeployed US Army soldiers. DESIGN, SETTING, AND PARTICIPANTS: A
      representative cross-sectional survey of 5428 nondeployed soldiers participating
      in a group self-administered survey. MAIN OUTCOMES AND MEASURES: Lifetime
      suicidal ideation, suicide plans, and suicide attempts. RESULTS: The lifetime
      prevalence estimates of suicidal ideation, suicide plans, and suicide attempts
      are 13.9%, 5.3%, and 2.4%. Most reported cases (47.0%-58.2%) had pre-enlistment
      onsets. Pre-enlistment onset rates were lower than in a prior national civilian
      survey (with imputed/simulated age at enlistment), whereas post-enlistment onsets
      of ideation and plans were higher, and post-enlistment first attempts were
      equivalent to civilian rates. Most reported onsets of plans and attempts among
      ideators (58.3%-63.3%) occur within the year of onset of ideation. Post
      enlistment attempts are positively related to being a woman (with an odds ratio
      [OR] of 3.3 [95% CI, 1.5-7.5]), lower rank (OR = 5.8 [95% CI, 1.8-18.1]), and
      previously deployed (OR = 2.4-3.7) and are negatively related to being unmarried
      (OR = 0.1-0.8) and assigned to Special Operations Command (OR = 0.0 [95% CI, 0.0
      0.0]). Five mental disorders predict post-enlistment first suicide attempts in
      multivariate analysis: pre-enlistment panic disorder (OR = 0.1 [95% CI, 0.0
      0.8]), pre-enlistment posttraumatic stress disorder (OR = 0.1 [95% CI, 0.0-0.7]),
      post-enlistment depression (OR = 3.8 [95% CI, 1.2-11.6]), and both pre- and post
      enlistment intermittent explosive disorder (OR = 3.7-3.8). Four of these 5 ORs
      (posttraumatic stress disorder is the exception) predict ideation, whereas only
      post-enlistment intermittent explosive disorder predicts attempts among ideators.
      The population-attributable risk proportions of lifetime mental disorders
      predicting post-enlistment suicide attempts are 31.3% for pre-enlistment onset
      disorders, 41.2% for post-enlistment onset disorders, and 59.9% for all
      disorders. CONCLUSIONS AND RELEVANCE: The fact that approximately one-third of
      post-enlistment suicide attempts are associated with pre-enlistment mental
      disorders suggests that pre-enlistment mental disorders might be targets for
      early screening and intervention. The possibility of higher fatality rates among
      Army suicide attempts than among civilian suicide attempts highlights the
      potential importance of means control (ie, restricting access to lethal means
      [such as firearms]) as a suicide prevention strategy.

PMID- 24590181
TI  - The global burden of other musculoskeletal disorders: estimates from the Global
      Burden of Disease 2010 study.
AB  - OBJECTIVE: To estimate disability from the remainder of musculoskeletal (MSK)
      disorders (categorised as other MSK) not covered by the estimates made
      specifically for osteoarthritis (OA), rheumatoid arthritis (RA), gout, low back
      pain and neck pain, as part of the Global Burden of Disease (GBD) 2010 study.
      METHODS: Systematic reviews were conducted to gather the age-sex-specific
      epidemiological data for other MSK. The focus was on finding health surveys and
      published studies that measured the overall amount of MSK disorders and
      complaints, and classified the remainder of MSK disorders that was not RA, OA,
      gout, low back or neck pain. Six levels of severity were defined to derive
      disability weights (DWs) and severity distribution. The data, DWs and severity
      distribution were used to calculate years of life lived with disability (YLDs).
      Mortality was estimated for MSK-related deaths classified under other MSK. YLDs
      were added to years of life lost (YLLs) from the mortality estimates to derive
      overall burden in disability-adjusted life years (DALYs). RESULTS: Global
      prevalence of other MSK was 8.4% (95% uncertainty interval (UI) 8.1% to 8.6%).
      DALYs increased from 20.6 million (95% UI 17.0 to 23.3 million) in 1990 to 30.9
      million (95% UI 25.8 to 34.6 million) in 2010. The burden of other MSK increased
      with age. Globally, other MSK disability burden (YLD) ranked sixth. CONCLUSIONS:
      Ageing of the global population will further increase the burden of other MSK.
      Specific MSK conditions within this large category should be considered
      separately to enable more explicit estimates of their burden in future iterations
      of GBD.

PMID- 24590182
TI  - The global burden of gout: estimates from the Global Burden of Disease 2010
      study.
AB  - OBJECTIVE: Gout is the most common cause of inflammatory arthritis in men, but
      has not previously been included in Global Burden of Disease (GBD) studies. As
      part of the GBD 2010 Study, the Musculoskeletal Disorders and Risk Factors Expert
      Group estimated the global burden of gout. METHODS: The American Rheumatism
      Association 1977 case definition of primary gout was used in the study. A series
      of systematic reviews were conducted to gather the age-specific and sex-specific
      epidemiological data for gout prevalence, incidence, mortality risk and duration.
      Two main disabling sequelae of gout were identified; acute episode gout and
      chronic polyarticular gout, and used in the surveys to collect data to derive
      disability weights. The epidemiological data together with disability weights
      were then used to calculate years of life lived with disability (YLDs) for gout,
      for 1990 and 2010. No evidence of cause-specific mortality associated with gout
      was found. Gout disability-adjusted life years (DALYs), therefore, have the same
      value as YLDs. RESULTS: Global prevalence of gout was 0.08% (95% uncertainty
      interval (UI) 0.07 to 0.08). DALYs increased from 76 000 (95% UI 48 to 112) in
      1990 to 114 000 (95% UI 72 to 167) in 2010. Out of all 291 conditions studied in
      the GBD 2010 Study, gout ranked 138th in terms of disability as measured by YLDs,
      and 173rd in terms of overall burden (DALYs). CONCLUSIONS: The burden of gout is
      rising. With increasing ageing populations globally, this evidence is a
      significant prompt to optimise treatment and management of gout at individual,
      community and national levels.

PMID- 24590183
TI  - A nine-dimensional global potential energy surface for NH4(X(2)A(1)) and kinetics
      studies on the H + NH3<-> H2 + NH2 reaction.
AB  - Extensive ab initio calculations of the stationary points in the NH4(X(2)A1)
      system are reported using both coupled cluster and multi-reference configuration
      interaction methods. In addition, more than 100 000 points are generated over a
      large configuration space and energy range (6 eV) using the explicitly correlated
      unrestricted coupled cluster method with single, double, and perturbative triple
      excitations with the augmented correlation-consistent polarized triple zeta basis
      set (UCCSD(T)-F12a/aug-cc-pVTZ). Using the recently proposed permutation
      invariant polynomial neural network (PIP-NN) method, these points are accurately
      fit to an analytical form with a total root mean squared error (RMSE) of 3.4 meV
      (0.08 kcal mol(-1)). Both the abstraction and exchange channels as well as the
      metastable ammonium radical (NH4) are included in this potential energy surface.
      Transition-state theory and quasi-classical trajectory calculations have been
      performed to obtain the rate constants for the abstraction reaction and its
      reverse. Comparison with available experimental results is satisfactory,
      providing supporting evidence for the accuracy of the potential. 

PMID- 24590184
TI  - Therapy. Cortisol rhythms in Addison disease.

PMID- 24590185
TI  - Metabolism: Tick, tock, a high-fat clock.

PMID- 24590186
TI  - Obesity: Genes and a hearty appetite conspire to increase childhood obesity risk.

PMID- 24590187
TI  - An innovative smartphone-based otorhinoendoscope and its application in mobile
      health and teleotolaryngology.
AB  - BACKGROUND: The traditional otorhinoendoscope is widely used in the diagnosis of
      a variety of ear and nose diseases, but only one doctor can use it at a time. It
      is also very difficult to share observations from one doctor with another doctor.
      With advances in electronic health technology, the extended potential application
      of smartphones to support medical practice or mobile health has grown steadily.
      OBJECTIVE: The first phase of the study discussed how smartphones may be used for
      otorhinoscopic imaging and image management via an innovative adaptor. The second
      phase of the study was to evaluate the diagnostic capability of the smartphone
      based otorhinoendoscope, as compared to the traditional otorhinoendoscope, and
      its application in mobile health and teleotolaryngology. METHODS: We designed a
      unique adaptor to connect the otorhinoendoscope and smartphone in order to
      perform smartphone-based otorhinoendoscopy. The main aim was to transform the
      smartphone into an otorhinoendoscope. We devised a method that would allow us to
      use the smartphone's camera to capture otorhinoscopic images. Using a freely
      available Web-based real-time communication application platform and the 3G (or
      WIFI) network, the smartphone-based otorhinoendoscope could synchronize the
      smartphone-based otorhinoscopic image with smartphones, tablet PCs, computer
      notebooks, or personal computers. RESULTS: We investigated the feasibility of
      telemedicine using a smartphone, tablet PC, and computer notebook. Six types of
      clinical otorhinoscopic images were acquired via the smartphone-based
      otorhinoendoscope from six patients, which were examined in this study. Three
      teleconsultants (doctors A, B, and C) reviewed the six types of clinical
      otorhinoscopic images and made a telediagnosis. When compared to the face-to-face
      diagnosis, which was made in-person via a traditional otorhinoendoscope, the
      three teleconsultants obtained scores of a correct primary telediagnosis 83%
      (5/6), 100% (6/6), and 100% (6/6) of the time, respectively. When the clinical
      data were provided, the three teleconsultants obtained a correct secondary
      telediagnosis score of 100% (6/6), 100% (6/6), and 100% (6/6) of the time,
      respectively. CONCLUSIONS: The use of previously available technologies in the
      absence of any additional expensive devices could significantly increase the
      quality of diagnostics while lowering extraneous costs. Furthermore, this could
      also increase the connectivity between most isolated family doctors and remote
      referral centers.

PMID- 24590188
TI  - Current developments in groundwater ecology--from biodiversity to ecosystem
      function and services.
AB  - Groundwater ecosystems constitute the largest terrestrial freshwater biome. They
      are dark, extremely low in energy and do not provide much space but they contain
      an unexpectedly high diversity of living forms showing characteristic adaptive
      features. The restricted accessibility along with the enormous 'invisible'
      heterogeneity challenged for a long time testing of scientific theories and
      unraveling of ecosystem functioning. Triggered by an improved
      interdisciplinarity, comprehensive sampling strategies and current developments
      in biotechnology and statistical analysis, groundwater ecology gains momentum
      entering a new era of research. We are only beginning to understand adaptive
      mechanisms, species distribution patterns and ecosystem functioning. Ninety-five
      percent of global liquid freshwater is stored in the terrestrial subsurface
      constituting a major source of water for drinking, irrigation and industrial
      purposes. There is an urgent need to integrate evolutionary and ecological
      research for developing a holistic perspective of the functional roles of
      biodiversity and ecosystem services and predicting global changes under
      alternative groundwater resource use scenarios. 

PMID- 24590189
TI  - Advances in solid-state NMR of cellulose.
AB  - Nuclear magnetic resonance (NMR) spectroscopy is a well-established analytical
      and enabling technology in biofuel research. Over the past few decades,
      lignocellulosic biomass and its conversion to supplement or displace non
      renewable feedstocks has attracted increasing interest. The application of solid
      state NMR spectroscopy has long been seen as an important tool in the study of
      cellulose and lignocellulose structure, biosynthesis, and deconstruction,
      especially considering the limited number of effective solvent systems and the
      significance of plant cell wall three-dimensional microstructure and component
      interaction to conversion yield and rate profiles. This article reviews common
      and recent applications of solid-state NMR spectroscopy methods that provide
      insight into the structural and dynamic processes of cellulose that control bulk
      properties and biofuel conversion. 

PMID- 24590190
TI  - Liquid chromatographic enzymatic studies with on-line Beta-secretase immobilized
      enzyme reactor and 4-(4-dimethylaminophenylazo) benzoic acid/5-[(2-aminoethyl)
      amino] naphthalene-1-sulfonic acid peptide as fluorogenic substrate.
AB  - High throughput screening (HTS) techniques are required for the fast hit
      inhibitors selection in the early discovery process. However, in Beta-secretase
      (BACE1) inhibitors screening campaign, the most frequently used methoxycoumarin
      based peptide substrate (M-2420) is not widely applicable when aromatic or
      heterocycle compounds of natural source show auto-fluorescence interferences.
      Here, in order to overcome these drawbacks, we propose the use of a highly
      selective 4-(4-dimethylaminophenylazo)benzoic acid/5-[(2
      aminoethyl)amino]naphthalene-1-sulfonic acid (DABCYL/1,5-EDANS) based peptide
      substrate (Substrate IV), whose cleavage product is devoid of spectroscopic
      interference. HrBACE1-IMER was prepared and characterized in terms of units of
      immobilised hrBACE1. BACE1 catalyzed Substrate IV cleavage was on-line
      kinetically characterized in terms of KM and vmax, in a classical Michaelis and
      Menten study. The on-line kinetic constants were found consistent with those
      obtained with the in solution fluorescence resonance energy transfer (FRET)
      standard method. In order to further validate the use of Substrate IV for
      inhibition studies, the inhibitory potency of the well-known BACE1 peptide
      InhibitorIV (IC50: 0.19+/-0.02MUM) and of the natural compound Uleine (IC50:
      0.57+/-0.05) were determined in the optimized on-line hrBACE1-IMER. The IC50
      values on the hrBACE1-IMER system were found in agreement with that obtained by
      the conventional methods confirming the applicability of Substrate IV for on-line
      BACE1 kinetic and inhibition studies. 

PMID- 24590191
TI  - An evaluation of washing and extraction techniques in the analysis of ethyl
      glucuronide and fatty acid ethyl esters from hair samples.
AB  - Ethyl glucuronide (EtG) and fatty acid ethyl esters (FAEEs) are alcohol
      metabolites measured in hair and are after a decade of research thought to be the
      best markers in hair to indicate alcoholism and abstinence Forensic Sci. Int. 218
      (2012) 2. A great body of work concerning EtG and FAEEs detection in hair has
      been performed. However, no recent extensive comparison has been made concerning
      washing and extraction procedures. This work shows that the washing procedure of
      dichloromethane followed by a methanol rinse of the hair sample removes more than
      16% of the FAEEs and 50% of the total EtG that is present in and on the hair. A
      review of ten washing protocols (where the removal is categorised: high, medium
      or low) showed that a relatively high percentage of FAEEs was removed and
      "medium" amount of EtG compared to the other washing protocols. This work shows
      promising results for the extraction of the FAEEs and the combined extraction of
      FAEEs and EtG by using 30min of sonication with methanol. More FAEEs were
      recovered from hair with methanol than with any other extraction solvent
      including the commonly used dimethyl sulfoxide/heptane mixture. When the
      sonication time was increased a higher percentage of transesterification of the
      FAEEs was observed, the extraction was "dirtier" as solids and a colour change
      was observed whereas the extraction efficiency did not increase. Therefore,
      washing the hair sample with dichloromethane and methanol followed by an addition
      of 1ml of methanol and sonication for 30min to extract the FAEEs and EtG from
      hair is recommended for FAEEs as well as for the combined analysis of EtG and
      FAEEs. A linear calibration curve (r(2)>0.99) was obtained for all analytes. 

PMID- 24590192
TI  - Measurement of Acoustic Transients During Pulsed Holmium:YAG Laser Ablation of
      Cadaveric Human Temporal Bone.
AB  - Pulsed infrared (IR) and ultraviolet (UV) lasers have been suggested for use in
      middle ear surgery due to potential fiberoptic delivery, decreased thermal trauma
      and precise ablation characteristics. Although attention has been focused on the
      thermal and photoacoustic events that occur during pulsed laser ablation of hard
      tissue, there are few studies which evaluate the acoustic energy generated from
      these devices from an audiological standpoint. In this study, the mastoid
      cavities of cadaveric human temporal bones were irradiated with a holmium:
      yttrium aluminium garnet (Ho:YAG) laser (lambda=2.12 um) using the following
      parameters: 5, 10, and 15 Hz pulse repetition rate and 1, 2, 4, 6, 8, and 10 W
      average power. During ablation, acoustic measurements were made using a sound
      level meter positioned 5 cm away from the target site. With each set of laser
      parameters, the sound intensity exceeded 85 dB (dBA scale). Peak intensities of
      125 dB were measured, and a saturation effect noted above 4 W or 500 mJ/pulse.
      The clinical significance of these findings is discussed and the acoustical
      aspects of middle ear function and noise trauma are reviewed. 

PMID- 24590193
TI  - Multifibre Application in Laser-Induced Interstitial Thermotherapy under On-Line
      MR Control.
AB  - .The application of multiple fibres for the conformal irradiation of tumours by
      laser-induced interstitial thermotherapy (LITT) has been investigated. A study
      was performed to evaluate the coagulated zones produced in porcine muscle tissue
      in vitro. For delivering specified powers into the tissue, a multifibre system
      was developed which allows the simultaneous use of up to four fibres. A new
      quantitative method of magnetic resonance imaging (MRI) has been applied for real
      time thermometry. It is based on the temperature dependence of the T1 relaxation
      time and the equilibrium magnetisation. The MR results were compared with the
      measurements of fibreoptic thermometers. Since the acquisition time of the
      selected MR sequence takes only 3 s per slice and the calculation of the
      temperature measurement could be realised within a few seconds, the temperature
      mapping works closely to real time. The accuracy of the temperature measurements
      in muscle tissue was 1.5 degrees C. Whereas single-fibre applications induced
      convex-shaped isotherms, concave structures were generated by a multifibre LITT. 

PMID- 24590194
TI  - Scanning Force Microscopy of the Fine Structure of Cartilage Irradiated with a
      CO2 Laser.
AB  - Alterations of the cartilage matrix structure under non-destructive laser
      irradiation have been investigated by scanning force microscopy. Porcine nasal
      septum cartilage was irradiated with a CO2 laser with a power density of 50
      W/cm(2) under two different time regimes: for 3 s and for 30 s. Short-time
      irradiation had little effect on the structure of the cartilage matrix. In
      comparison with non-irradiated cartilage, small channels of 100-400 nm in cross
      section appeared. This observation gives evidence that the underlying mechanism
      of laser-induced stress relaxation of cartilage is based on short-time
      depolymerisation and subsequent re-formation of proteoglycan units. The 30 s
      laser treatment results in melting and denaturation of the matrix. For the first
      time, small crystals, 100-800 nm, were found on cut sections of the laser treated
      cartilage. The crystals mainly consist of resolvable sodium carbonate. Thus, they
      cannot be responsible for the formation of a stable cartilage configuration after
      laser treatment. 

PMID- 24590195
TI  - Inactivation of Proteolytic Enzymes from Porphyromonas gingivalis Using Light
      activated Agents.
AB  - Previous studies have shown one of the causative agents of periodontitis,
      Porphyromonas gingivalis, can be killed by red light in the presence of the light
      activated antimicrobial agent toluidine blue O (TBO). The purpose of this study
      was to determine the effects of irradiating the organism with red light in the
      presence of TBO on its proteolytic enzyme activity.Suspensions of P. gingivalis
      were exposed to light with a wavelength of 633 nm in the presence of various
      concentrations of TBO. Samples were taken at various times and their proteolytic
      activity determined by assay of azocasein hydrolysis. On exposure to 126 J of red
      light in the presence of 12.5 ug/ml of TBO the proteolytic enzyme activity was
      reduced by 100%.The results of this study have shown that the main virulence
      factor of P. gingivalis, its proteolytic activity, can be inactivated by red
      light in the presence of TBO. This, together with the known bactericidal activity
      of the TBO/light combination, suggests that photodynamic therapy may prove
      important in reducing the effectiveness of P. gingivalis as a periodontopathogen
      in vivo. 

PMID- 24590196
TI  - Effect of photodynamic therapy on the mechanical strength of healed rodent skin
      incisions.
AB  - A factor that might complicate the use of intraoperative photodynamic therapy
      (PDT) is a possible adverse effect on normal tissue recovery. In this study, rats
      with experimental skin incisions received intraoperative PDT (10 mg/kg
      haematoporphyrin derivative, 180 J/cm(2) laser light), immediately followed by
      closure. Healing was evaluated by tensile strength assessment of the incisions 21
      days after PDT. No significant differences between the PDT-treated group and
      control groups were found. We therefore concluded that with respect to healing of
      skin incisions in rats, intraoperative PDT is not contraindicated. 

PMID- 24590197
TI  - Reduction of Plasminogen Activator Activity Stimulated by Lipopolysaccharide from
      Periodontal Pathogen in Human Gingival Fibroblasts by Low-energy Laser
      Irradiation.
AB  - Human gingival fibroblasts (hGF) reside in gingival tissues which are challenged
      frequently by oral bacteria. Lipopolysaccharide (LPS) from periodontal pathogens
      can penetrate gingival tissues and stimulate plasminogen activator (PA) activity
      which is implicated in the PA/plasmin proteolytic system. The PA/plasmin system
      plays an important role in the degradation of the extracellular matrix and
      synthesis of kinin in the process of inflammation. Anti-inflammatory effects by
      low-energy laser irradiation have been reported. However, the mechanisms of
      biostimulatory effects have not been elucidated in detail. The primarily cultured
      hGF cells were challenged with LPS isolated from Campylobacter rectus which was
      known as a periodontal pathogen and Ga-Al-As diode low energy laser was
      irradiated (830 nm, 7.90 J/cm(2)). The cultured medium of hGF cells showed a
      marked elevation in PA activity by LPS, which was significantly inhibited by the
      laser irradiation in a dose-dependent manner. This effect was involved in the
      reduction of tPA mRNA levels. 

PMID- 24590198
TI  - Tumour cell damage and leucocyte infiltration after laser immunotherapy
      treatment.
AB  - Immune response after laser-photosensitiser application could be crucial in
      treatment of cancers, because without it there could be no systemic, long-term
      tumour control. Laser immunotherapy, a novel method for treatment of metastatic
      tumours, uses a near-infrared laser, a laser-absorbing dye indocyanine green, and
      an immunoadjuvant glycated chitosan. This modality has shown an induced
      antitumour immune response in treatment of rat mammary metastatic tumours. The
      influence of this new method on the cellular structure of the tumours and on the
      infiltrating immune cells was studied using optical and electron microscopes. The
      tumour samples were examined before and immediately after the treatment for acute
      effects, which appeared mainly photothermal. Two weeks after treatment,
      significant infiltrating lymphocytes and plasma cells were found around the
      surviving tumour cells. These morphological findings suggest that both cell
      mediated and humoral immune responses could be responsible for the observed
      tumour eradication and induced long-term tumour resistance. 

PMID- 24590199
TI  - Monte carlo simulations of light distributions in an embedded tumour model:
      studies of selectivity in photodynamic therapy.
AB  - It is well known that photosensitisers in photodynamic therapy (PDT) tend to
      localise in greater concentrations in tumours. This attractive feature may help
      confer on PDT the potential to selectivity destroy tumours while sparing the
      surrounding normal tissue. In this paper Monte Carlo simulations were used to
      study light distributions in a simple model consisting of tumour embedded in
      surrounding normal tissue subjected to superficial irradiance. The Monte Carlo
      model was coded to allow modelling of arbitrary geometries and multiple tissue
      types. This permitted the use of different optical properties for tumour and
      normal tissue. Two simulations were run using optical coefficients appropriate to
      breast carcinoma in adipose tissue and liver tumour in liver. Contours of equal
      fluence were plotted against depth for both simulations. Contours of equal
      photodynamic dose (fluence*drug concentration) were plotted for various
      tumour/normal drug ratios. By assuming a threshold for necrosis it was possible
      to estimate the depth of damage in the normal tissue and tumour simultaneously. A
      greater depth of selective tumour damage was observed in the breast tissue
      simulation for a given drug ratio due to the higher penetration of light compared
      to the liver. For a tumour to normal ratio of 4:1 selective damage to a depth
      greater than 4 mm was observed in the breast simulation compared to almost 3 mm
      in the case of the liver model. 

PMID- 24590201
TI  - Fluorescence Photodiagnostics and Photobleaching Studies of Cancerous Lesions
      using Ratio Imaging and Spectroscopic Techniques.
AB  - Topical or systemic administration of 5-aminolaevulinic acid results in
      biosynthesis of the photosensitiser protoporphyrin IX (PpIX) with some
      selectivity for malignant lesions. Excitation near 400 nm excites both intrinsic
      green tissue autofluorescence and red fluorescence from PpIX which may be
      exploited for the optical diagnosis of malignant and premalignant disease. In
      this work the utility of a cooled 12-bit single chip charge-coupled device (CCD)
      colour camera was investigated for photodiagnostic fluorescence ratio imaging.
      The red to green fluorescence intensity ratios were calculated for each pixel in
      real-time and fluorescence ratio images were displayed typically at a rate of 2
      frames/s. Laboratory tests of fluorescence ratio imaging showed good contrast
      enhancement between control tissues and tissue phantoms and those containing
      porphyrin photosensitisers. In preliminary clinical tests, a clear demarcation
      between neoplastic/cancerous lesions and adjacent normal tissue was demonstrated.
      The extent of PpIX photobleaching during photodynamic therapy was also
      investigated using fluorescence ratio imaging. 

PMID- 24590200
TI  - Specific effects of laserpuncture on the cerebral circulation.
AB  - Acupuncture is a form of traditional Chinese medicine that has developed over
      thousands of years. We studied the effects of laser puncture, needle acupuncture,
      and light stimulation on cerebral blood flow in 15 healthy volunteers (mean age
      25.0+/-1.9 years, 5 female, 10 male) with non-invasive transcranial Doppler
      sonography. In addition 40-Hz stimulus-induced brain oscillations, heart rate,
      blood pressure, peripheral and cerebral oxygen saturation, and the bispectral
      index of the EEG were recorded. Stimulation with light significantly increased
      blood flow velocity in the posterior cerebral artery (p<0.01, ANOVA). Similar but
      less pronounced effects were seen after needle acupuncture (p< 0.05, ANOVA) and
      laserpuncture (n.s.) of vision-related acupuncture points. Furthermore both,
      laserpuncture and needle acupuncture, led to a significant increase in the
      amplitudes of 40-Hz cerebral oscillations. Stimulation of vision-related
      acupuncture points with laser light or needle acupuncture elicits specific
      effects in specific areas of the brain. The results indicate that the brain plays
      a key intermediate role in acupuncture. However, brain activity of itself does
      not explain anything about the healing power of acupuncture. 

PMID- 24590202
TI  - Laser therapy of monochorionic twin-twin transfusion syndrome pregnancies.

PMID- 24590203
TI  - Effect of corn steep liquor (CSL) and cassava wastewater (CW) on chitin and
      chitosan production by Cunninghamella elegans and their physicochemical
      characteristics and cytotoxicity.
AB  - Microbiological processes were used for chitin and chitosan production with
      Cunninghamella elegans UCP/WFCC 0542 grown in different concentrations of two
      agro-industrial wastes, corn steep liquor (CSL) and cassava wastewater (CW)
      established using a 22 full factorial design. The polysaccharides were extracted
      by alkali-acid treatment and characterized by infrared spectroscopy, viscosity,
      thermal analysis, elemental analysis, scanning electron microscopy and X-ray
      diffraction. The cytotoxicity of chitosan was evaluated for signs of vascular
      change on the chorioallantoic membrane of chicken eggs. The highest biomass (9.93
      g/L) was obtained in trial 3 (5% CW, 8% CSL), the greatest chitin and chitosan
      yields were 89.39 mg/g and 57.82 mg/g, respectively, and both were obtained in
      trial 2 (10% CW, 4% CSL). Chitin and chitosan showed a degree of deacetylation of
      40.98% and 88.24%, and a crystalline index of 35.80% and 23.82%, respectively,
      and chitosan showed low molecular weight (LMW 5.2 * 103 Da). Chitin and chitosan
      can be considered non-irritating, due to the fact they do not promote vascular
      change. It was demonstrated that CSL and CW are effective renewable
      agroindustrial alternative substrates for the production of chitin and chitosan.

PMID- 24590204
TI  - Highly reduced mass loss rates and increased litter layer in radioactively
      contaminated areas.
AB  - The effects of radioactive contamination from Chernobyl on decomposition of plant
      material still remain unknown. We predicted that decomposition rate would be
      reduced in the most contaminated sites due to an absence or reduced densities of
      soil invertebrates. If microorganisms were the main agents responsible for
      decomposition, exclusion of large soil invertebrates should not affect
      decomposition. In September 2007 we deposited 572 bags with uncontaminated dry
      leaf litter from four species of trees in the leaf litter layer at 20 forest
      sites around Chernobyl that varied in background radiation by more than a factor
      2,600. Approximately one quarter of these bags were made of a fine mesh that
      prevented access to litter by soil invertebrates. These bags were retrieved in
      June 2008, dried and weighed to estimate litter mass loss. Litter mass loss was
      40% lower in the most contaminated sites relative to sites with a normal
      background radiation level for Ukraine. Similar reductions in litter mass loss
      were estimated for individual litter bags, litter bags at different sites, and
      differences between litter bags at pairs of neighboring sites differing in level
      of radioactive contamination. Litter mass loss was slightly greater in the
      presence of large soil invertebrates than in their absence. The thickness of the
      forest floor increased with the level of radiation and decreased with
      proportional loss of mass from all litter bags. These findings suggest that
      radioactive contamination has reduced the rate of litter mass loss, increased
      accumulation of litter, and affected growth conditions for plants.

PMID- 24590206
TI  - Chiral rhodium complexes covalently anchored on carbon nanotubes for
      enantioselective hydrogenation.
AB  - Chiral rhodium hybrid nanocatalysts have been prepared by covalent anchorage of
      pyrrolidine-based diphosphine ligands onto functionalized CNTs. This work
      constitutes the first attempt at covalent anchoring of homogeneous chiral
      catalysts on CNTs. The catalysts, prepared with two different chiral phosphines,
      were characterized by ICP, XPS, N2 adsorption and TEM, and have been tested in
      the asymmetric hydrogenation of two different substrates: methyl 2
      acetamidoacrylate and alpha-acetamidocinnamic acid. The hybrid nanocatalysts have
      shown to be active and enantioselective in the hydrogenation of alpha
      acetamidocinnamic acid. A good recyclability of the catalysts with low leaching
      and without loss of activity and enantioselectivity was observed. 

PMID- 24590207
TI  - Comparison of new modeling methods for postnatal weight in ELBW infants using
      prenatal and postnatal data.
AB  - OBJECTIVES: Postnatal infant weight curves are used to assess fluid management
      and evaluate postnatal nutrition and growth. Traditionally, postnatal weight
      curves are based on birth weight and do not incorporate postnatal clinical
      information. The aim of the present study was to compare the accuracy of birth
      weight-based weight curves with weight curves created from individual patient
      records, including electronic records, using 2 predictive modeling methods,
      linear regression (LR) and an artificial neural network (NN), which apply
      mathematical relations between predictor and outcome variables. METHODS:
      Perinatal demographic and postnatal nutrition data were collected for extremely
      low-birth-weight (ELBW; birth weight <1000 g) infants. Static weight curves were
      generated using published algorithms. The postnatal predictive models were
      created using the demographic and nutrition dataset. RESULTS: Birth weight (861
      +/- 83 g, mean +/- 1 standard deviation [SD]), gestational age (26.2 +/- 1.4
      weeks), and the first month of nutrition data were collected from individual
      health records for 92 ELBW infants. The absolute residual (|measured-predicted|)
      for weight was 84.8 +/- 74.4 g for the static weight curves, 60.9 +/- 49.1 g for
      the LR model, and 12.9 +/- 9.2 g for the NN model, analysis of variance: both LR
      and NN P<0.01 versus static curve. NPO (nothing by mouth) infants had greater
      weight curve discrepancies. CONCLUSIONS: Compared with birth weight-based and
      logistic regression-generated weight curves, NN-generated weight curves more
      closely approximated ELBW infant weight curves, and, using the present electronic
      health record systems, may produce weight curves better reflective of the
      patient's status.

PMID- 24590205
TI  - Attracted to the enemy: Aedes aegypti prefers oviposition sites with predator
      killed conspecifics.
AB  - Oviposition habitat choices of species with aquatic larvae are expected to be
      influenced by both offspring risk of mortality due to predation, and offspring
      growth potential. Aquatic predators may indirectly influence growth potential for
      prey by reducing prey density and, for filter-feeding prey, by increasing
      bacterial food for prey via added organic matter (feces, partially eaten
      victims), creating the potential for interactive effects on oviposition choices.
      We tested the hypothesis that the mosquito Aedes aegypti preferentially oviposits
      in habitats with predatory Toxorhynchites larvae because of indirect effects of
      predation on chemical cues indicating bacterial abundance. We predicted that A.
      aegypti would avoid oviposition in sites with Toxorhynchites, but prefer to
      oviposit where bacterial food for larvae is abundant, and that predation by
      Toxorhynchites would increase bacterial abundances. Gravid A. aegypti were
      offered paired oviposition sites representing choices among: predator presence;
      the act of predation; conspecific density; dead conspecific larvae; and bacterial
      activity. A. aegypti preferentially oviposited in sites with Toxorhynchites
      theobaldi predation, and with killed conspecific larvae, but failed to detect
      preferences for other treatments. The antibiotic tetracycline eliminated the
      strongest oviposition preference. Both predation by Toxorhynchites and killed
      larvae increased bacterial abundances, suggesting that oviposition attraction is
      cued by bacteria. Our results show the potential for indirect effects, like
      trophic cascades, to influence oviposition choices and community composition in
      aquatic systems. Our results suggest that predators like Toxorhynchites may be
      doubly beneficial as biocontrol agents because of the attraction of ovipositing
      mosquitoes to bacterial by-products of Toxorhynchites feeding. 

PMID- 24590209
TI  - Risk stratification for the use of thromboprophylaxis in young people With IBD
      requires further evaluation.

PMID- 24590210
TI  - Allopurinol: a useful adjunct to thiopurine therapy for pediatric ulcerative
      colitis in the biologic era.
AB  - Thiopurines are used as a maintenance therapy in patients with ulcerative colitis
      (UC). For some patients the metabolism of thiopurines is unfavorable, leading to
      increased adverse effects, including hepatotoxicity. There are many reports in
      the adult literature concerning the manipulation of thiopurine metabolism with
      allopurinol; however, there is only 1 publication in this respect for pediatric
      UC. We present 3 pediatric cases of UC wherein the combination of allopurinol and
      low-dose 6-mercaptopurine allowed for shunting of thiopurine metabolites to a
      more favorable pattern. This intervention supported clinical remission in all,
      including one case poorly responsive to infliximab. 

PMID- 24590208
TI  - Smad3-deficient mice have reduced esophageal fibrosis and angiogenesis in a model
      of egg-induced eosinophilic esophagitis.
AB  - OBJECTIVES: Eosinophilic esophagitis (EoE) is a food-triggered disease associated
      with esophageal fibrosis and stricture formation in a subset of patients. In the
      present study we used a murine model of egg (ovalbumin [OVA])-induced EoE to
      determine whether inhibiting transforming growth factor-beta1 (TGF-beta1)
      signaling through the Smad3 pathway would inhibit features of esophageal
      remodeling including fibrosis, angiogenesis, and basal zone hyperplasia. METHODS:
      Wild-type (WT) and Smad3-deficient (KO [knockout]) mice were sensitized
      intraperitoneally and then challenged chronically with intraesophageal OVA for 1
      month. Levels of esophageal eosinophils, esophageal TGF-beta1+ and vascular
      endothelial growth factor (VEGF)+ cells, and features of esophageal remodeling
      (fibrosis, angiogenesis, basal zone hyperplasia) were quantitated by
      immunohistochemistry and image analysis. RESULTS: OVA challenge induced a similar
      increase in the levels of esophageal major basic protein (MBP)+ eosinophils and
      esophageal TGF-beta1+ cells in WT and Smad3 KO mice. Smad3 KO mice challenged
      with OVA had significantly less esophageal fibrosis and esophageal angiogenesis
      compared with OVA-challenged WT mice. The reduced esophageal angiogenesis in
      Smad3 KO mice was associated with reduced numbers of VEGF+ cells in the
      esophagus. There was a trend toward OVA-challenged Smad3 KO to have reduced basal
      zone hyperplasia, but this was not statistically significant. CONCLUSIONS: In a
      mouse model of egg-induced EoE, Smad3-deficient mice have significantly less
      esophageal remodeling, especially fibrosis and angiogenesis that is associated
      with reduced expression of VEGF. Targeting the TGF-beta1/Smad3 pathway may be a
      novel strategy to reduce esophageal fibrosis and its associated complications
      such as esophageal strictures in EoE.

PMID- 24590212
TI  - Myofibroblastic Tumor of the Pancreatic Head: Recurrent Cholangitis.

PMID- 24590211
TI  - Lactobacilli and bifidobacteria in human breast milk: influence of antibiotherapy
      and other host and clinical factors.
AB  - OBJECTIVE: The objective of this work was to study the lactobacilli and
      bifidobacteria population in human milk of healthy women, and to investigate the
      influence that several factors (including antibioteraphy during pregnancy and
      lactation, country and date of birth, delivery mode, or infant age) may exert on
      such population. METHODS: A total of 160 women living in Germany or Austria
      provided the breast milk samples. Initially, 66 samples were randomly selected
      and cultured on MRS-Cys agar plates. Then, the presence of DNA from the genera
      Lactobacillus and Bifidobacterium, and from most of the Lactobacillus and
      Bifidobacterium species that were isolated, was assessed by qualitative
      polymerase chain reaction (PCR) using genus- and species-specific primers.
      RESULTS: Lactobacilli and bifidobacteria could be isolated from the milk of 27
      (40.91%) and 7 (10.61%), respectively, of the 66 cultured samples. On the
      contrary, Lactobacillus and Bifidobacterium sequences were detected by PCR in 108
      (67.50%) and 41 (25.62%), respectively, of the 160 samples analyzed. The
      Lactobacillus species most frequently isolated and detected was L salivarius
      (35.00%), followed by L fermentum (25.00%) and L gasseri (21.88%), whereas B
      breve (13.75%) was the bifidobacterial species most commonly recovered and whose
      DNA was most regularly found. The number of lactobacilli- or bifidobacteria
      positive samples was significantly lower in women who had received antibiotherapy
      during pregnancy or lactation. CONCLUSIONS: Our results suggest that either the
      presence of lactobacilli and/or bifidobacteria or their DNA may constitute good
      markers of a healthy human milk microbiota that has not been altered by the use
      of antibiotics.

PMID- 24590213
TI  - Management of duodenal-jejunal polyps in children with peutz-jeghers syndrome
      with single-balloon enteroscopy.
AB  - OBJECTIVES: Children with Peutz-Jeghers syndrome (PJS) have increased risk of
      polyp-related complications and emergency laparotomies. The aim of the present
      study was to assess the efficacy and the safety of endoscopic therapy of small
      bowel polyps using single-balloon enteroscopy (SBE) in children affected by PJS.
      METHODS: Between January 2010 and December 2011, prospectively consecutive PJS
      children with polyps >15 mm or polyps actively bleeding previously identified
      using video capsule endoscopy and magnetic resonance imaging underwent
      therapeutic SBE. The main outcome measurements were the feasibility, the
      technical performance, and the safety. RESULTS: A total of 10 children (6 boys;
      median age 13.7 years, range 5.6-15.6) underwent 23 SBE procedures. Four patients
      had a history of abdominal surgery. A total of 53 polyps were removed, and 23 of
      them were >15 mm. The majority of polyps were found in jejunum (85%). The mean
      insertion depths for antegrade and retrograde approach were 200 +/- 80 and 100 +/
      50 cm beyond the ileal valve, respectively. The mean procedure time was 75 +/-
      25 minutes. Mild abdominal pain was reported after 3 procedures. In 1 patient a
      postpolypectomy perforation occurred. CONCLUSIONS: In conclusion, SBE is an
      effective endoscopic tool for treating small bowel polyps in children with PJS,
      and well-timed polypectomy may optimize patients' care, preventing polyp-related
      complications and emergency laparotomy. Further larger multicenter studies are
      warranted to accurately determine the safety of therapeutic SBE in children.

PMID- 24590214
TI  - Effects of 70% ethanol locks on rates of central line infection, thrombosis,
      breakage, and replacement in pediatric intestinal failure.
AB  - OBJECTIVES: Parenteral nutrition is essential for the growth and nutrition of
      patients with intestinal failure (IF). Catheter-related bloodstream infections
      (CRBSI) are a major complication of parenteral nutrition use. Few retrospective
      studies have shown that 70% ethanol lock (ETL) therapy for central lines can
      reduce the infection rate. Studies assessing line breakage, thrombosis, and
      replacement with the use of ETL are lacking in the pediatric literature. METHODS:
      The present study is a retrospective chart review, with a primary outcome of
      CRBSI rate per 1000 catheter days, and secondary outcomes of line thrombosis,
      line breakage requiring repair, and line replacement rates with use of ETL
      compared with heparin locks. Rates were compared using the Wilcoxon signed-rank
      test for paired nonparametric data. RESULTS: Seven patients satisfied the
      inclusion criteria that included having a single-lumen silicone central line
      exposed to both heparin and ETL therapy during the study period. There was a
      statistically significant decrease in overall and Gram-negative CRBSI rates per
      1000 catheter days with a use of ETL therapy (10.3-1.4 per 1000 catheter days for
      overall CRBSIs, P = 0.02; 6.7-0 per 1000 catheter days for Gram-negative CRBSI, P
      = 0.03). There was an increasing trend in line thrombosis and repair rates with
      ETL therapy. Logistic regression analysis evaluating the impact of line luminal
      size on line repair rate showed a reduced risk of line repair when using larger
      diameter central lines. CONCLUSIONS: ETL therapy is an effective method for
      decreasing CRBSI in patients with IF; however, it may have a negative impact on
      line integrity. Patients should be carefully selected when deciding on ETL
      therapy use for central line care. Studies are needed on the effect of different
      ethanol concentrations on infection rate and line integrity to optimize the
      outcome in this high-risk population.

PMID- 24590215
TI  - Topical mitomycin-C application in recurrent esophageal strictures after surgical
      repair of esophageal atresia.
AB  - OBJECTIVES: The aim of the present study was to evaluate the efficacy and short
      term safety of topical mitomycin-C, an antifibrotic agent, in preventing the
      recurrence of anastomotic strictures after surgical repair of esophageal atresia
      (EA). METHODS: We retrospectively reviewed the medical records of patients with
      recurrent anastomotic strictures after EA surgery who underwent at least 3
      esophageal dilations. We compared the outcome (ie, resolution of the stricture)
      of the group that received topical mitomycin-C treatment with endoscopic
      esophageal dilation with a historical cohort treated by dilations alone. RESULTS:
      A total of 11 children received mitomycin-C concurrently with endoscopic
      dilations. After a median follow-up of 33 months (range 18-72), and a mean number
      of 5.4 dilations per patient (range 3-11), 8 of 11 patients achieved a resolution
      of their strictures, 2 patients remained with stenosis, and 1 patient needed a
      surgical correction. In the control group, 10 patients required an average of 3.7
      (range 3-7) total dilations. After a follow-up of 125 months (range 35-266) after
      the last dilation, strictures in 9 of 10 children disappeared and the remaining
      patient was symptom free. No dysplasia related to mitomycin-C was demonstrated.
      CONCLUSIONS: There is no benefit in the resolution of the stricture when adding
      mitomycin-C treatment compared with repeated esophageal dilations alone in
      historical controls. Further randomized controlled studies and a short- and long
      term evaluation of safety are needed.

PMID- 24590216
TI  - Development of a self-efficacy scale for adolescents and young adults with
      inflammatory bowel disease.
AB  - BACKGROUND: Pediatric inflammatory bowel disease (IBD) self-management fits well
      within a social-cognitive framework. At the heart of social-cognitive theory is
      self-efficacy, a set of beliefs about one's ability to perform certain tasks.
      Self-efficacy is a strong predictor of health outcomes in chronic diseases and
      could serve as an intermediary outcome measure of self-management for pediatric
      IBD. The aim of this preliminary study was to develop items for the design of a
      self-efficacy scale specifically for adolescents and young adults with IBD.
      METHODS: Survey development is an iterative process. As defined by the US Food
      and Drug Administration guidelines for developing a patient-reported outcome
      measurement, the first step of this process is to obtain patient input. Using
      qualitative research methods, adolescents and young adults were recruited from an
      outpatient pediatric gastroenterology clinic to participate in a semistructured
      interview. Transcriptions of the recorded interviews were reviewed for themes
      related to self-efficacy around disease management. A consensus panel of
      gastroenterologists and health psychologists reviewed the initially constructed
      items. Those specific items were then reviewed and adjusted by a panel of
      participants for content and understandability using cognitive interview methods.
      The resulting 13-item scale is presented here. RESULTS: Nineteen patients and 5
      parents participated in the study. The study sample was 42% girls, 79% whites,
      74% had Crohn disease, and 79% had not required surgery. Median age was 15 years
      (range 10-22 years). Theme analysis and expert review yielded 13 items across 4
      theoretical domains: managing medical care, managing daily life with IBD,
      managing emotions, and managing the future with IBD. CONCLUSIONS: A 13-item
      disease-specific scale has been developed based on patient input to assess self
      efficacy around self-management in adolescents with IBD. Efforts to validate this
      newly designed scale are presently under way.

PMID- 24590217
TI  - Endoscopic Therapy for Complete Pancreatic Ductal Obstruction in a Child With
      Hereditary Pancreatitis.

PMID- 24590218
TI  - A Penny's Worth of Advice: Deep Esophageal Injury From a Coin.

PMID- 24590219
TI  - Baby Bottle Nipple Causing Small Bowel Obstruction.

PMID- 24590220
TI  - Development of the gastrointestinal endoscopy competency assessment tool for
      pediatric colonoscopy (GiECAT KIDS).
AB  - OBJECTIVES: Many aspects of pediatric colonoscopy differ from adult practice. To
      date, there is no validated measure of endoscopic competence for use in
      pediatrics. Using Delphi methodology, we aimed to determine expert consensus
      regarding items required on a checklist and global rating scale designed to
      assess the competence of clinicians performing colonoscopy on pediatric patients.
      METHODS: A total of 41 North American pediatric endoscopy experts rated potential
      checklist and global rating items for their importance as indicators of the
      competence of trainees learning to perform pediatric colonoscopy. Responses were
      analyzed and re-sent to the panel for further ratings until consensus was
      reached. Items that >= 80% of experts rated as >= 4 out of 5 were included in the
      final instrument. Consensus items were compared with those items deemed by adult
      endoscopy experts as fundamental to assessing the performance of adult
      colonoscopy. RESULTS: Five rounds of surveys were completed with response rates
      ranging from 76% to 100%. Seventy-five checklist and 38 global rating items were
      reduced to 18 checklist and 7 global rating items that reached consensus. Three
      pediatric checklist items differed from those considered to be critical adult
      indicators, whereas 4 items on the latter did not reach consensus among pediatric
      experts. CONCLUSIONS: Delphi methodology allowed for achievement of expert
      consensus regarding essential items to be included in the Gastrointestinal
      Endoscopy Competency Assessment Tool for Pediatric Colonoscopy (GiECATKIDS), a
      measure of endoscopic competence specific to performing pediatric colonoscopy.
      Key differences in the checklist items, compared with items reaching consensus
      during a separate adult Delphi process using the same indicators, emphasize the
      need for a pediatric-specific tool.

PMID- 24590221
TI  - Benefits of attending a summer camp for children with inflammatory bowel disease.
AB  - OBJECTIVES: The aim of the present study was to investigate knowledge of
      pediatric patients with inflammatory bowel disease (IBD) and perceptions of Camp
      Gut Busters, an IBD summer camp. METHODS: The present ethnographic study uses
      traditional anthropological methods to investigate participants' knowledge and
      perceptions of Camp Gut Busters. Data were gathered using in-depth qualitative
      interviews, participant observation during 4 Camp Gut Busters summer sessions,
      and attendance records for the summer camp. Participants either attended Camp Gut
      Busters (campers) or did not attend (noncampers). Campers' knowledge and
      perceptions were based on their actual experience at Camp Gut Busters, whereas
      those of noncampers were based on their expectations of camp. RESULTS:
      Participant responses reference their illness experience with IBD, their
      struggles of learning to live with a chronic condition, and the benefits of
      attending a disease-specific camp. Campers addressed notions of identity, the
      isolation associated with having a potentially stigmatizing chronic condition,
      therapeutic routines, and awareness of IBD. Noncampers focused on discomfort with
      IBD and their identity as an individual and child with the disease. CONCLUSIONS:
      Pediatric patients with IBD who attended a disease-specific summer camp benefited
      from the experience. Exposure to peers with similar therapeutic routines and to
      the range of IBD helped campers build an empathetic social network and introduced
      a new perspective on their disease. Attending a disease-specific camp helps
      pediatric patients with IBD in psychosocial adjustment and acquisition of
      knowledge about their disease. Ultimately, it helps them learn to live with their
      chronic condition.

PMID- 24590223
TI  - International Journal of Surgery. Editor's perspectives--April 2014.

PMID- 24590222
TI  - Authors' response.

PMID- 24590224
TI  - Action-derived molecular dynamics simulations for the migration and coalescence
      of vacancies in graphene and carbon nanotubes.
AB  - We report the results of action-derived molecular dynamics simulations for the
      migration and coalescence processes of monovacancies in graphene and carbon
      nanotubes with different chiralities. In carbon nanotubes, the migration pathways
      and barriers of a monovacancy depend on the tube chirality, while there is no
      preferential pathway in graphene due to the lattice symmetry and the absence of
      the curvature effect. The probable pathway changes from the axial to
      circumferential direction as the chirality varies from armchair to zigzag. The
      chirality dependence is attributed to the preferential orientation of the
      reconstructed bond formed around each vacancy site. It is energetically more
      favourable for two monovacancies to coalesce into a divacancy via alternative
      movements rather than simultaneous movements. The energy barriers for coalescence
      are generally determined by the migration barrier for the monovacancy, although
      there are some variations due to interactions between two diffusing vacancies. In
      graphene and armchair nanotubes, two monovacancies prefer to migrate along
      different zigzag atomic chains rather than a single atomic chain connecting these
      vacancies. On the other hand, in zigzag tubes, the energy barrier for coalescence
      increases significantly unless monovacancies lie on the same circumference. 

PMID- 24590225
TI  - Efficacy of brain-computer interface-driven neuromuscular electrical stimulation
      for chronic paresis after stroke.
AB  - OBJECTIVE: Brain computer interface technology is of great interest to
      researchers as a potential therapeutic measure for people with severe
      neurological disorders. The aim of this study was to examine the efficacy of
      brain computer interface, by comparing conventional neuromuscular electrical
      stimulation and brain computer interface-driven neuromuscular electrical
      stimulation, using an A-B-A-B withdrawal single-subject design. METHODS: A 38
      year-old male with severe hemiplegia due to a putaminal haemorrhage participated
      in this study. The design involved 2 epochs. In epoch A, the patient attempted to
      open his fingers during the application of neuromuscular electrical stimulation,
      irrespective of his actual brain activity. In epoch B, neuromuscular electrical
      stimulation was applied only when a significant motor-related cortical potential
      was observed in the electroencephalogram. RESULTS: The subject initially showed
      diffuse functional magnetic resonance imaging activation and small electro
      encephalogram responses while attempting finger movement. Epoch A was associated
      with few neurological or clinical signs of improvement. Epoch B, with a brain
      computer interface, was associated with marked lateralization of
      electroencephalogram (EEG) and blood oxygenation level dependent responses.
      Voluntary electromyogram (EMG) activity, with significant EEG-EMG coherence, was
      also prompted. Clinical improvement in upper-extremity function and muscle tone
      was observed. CONCLUSION: These results indicate that self-directed training with
      a brain computer interface may induce activity- dependent cortical plasticity and
      promote functional recovery. This preliminary clinical investigation encourages
      further research using a controlled design.

PMID- 24590226
TI  - Evolution: boom and robust.

PMID- 24590228
TI  - Gene expression: transcription initiation codes - the tip of the iceberg?

PMID- 24590229
TI  - Impacts of urbanization on groundwater hydrodynamics and hydrochemistry of the
      Toluca Valley aquifer (Mexico).
AB  - The Toluca Valley is located on the high plains of Mexico, where there are
      significant industrial zones and large populations. Water needs are almost
      exclusively met by groundwater, which has brought about intense exploitation of
      the aquifer and indication of some contamination. The present study investigates
      the effect of urbanization, related to industrialization of the region, on
      groundwater in the central portion of the Toluca Valley aquifer--a zone with high
      population density and where the largest industrial park is located. A general
      decline in the groundwater level has been found over the years, at a rate of as
      much as 2.5 m/year. The appearance of a large drawdown cone was identified,
      indicating changes in the direction of groundwater flow. Also identified was the
      presence of several ground fissures, the location of which coincided with the
      drawdown cone. In hydrochemical terms, the water type is sodium-magnesium
      bicarbonate and this characteristic has not changed over time, although it has
      been possible to detect the presence of larger quantities of sulfates (up to 117
      mg/L) and nitrates (up to 47 mg/L) in recent years, likely associated with
      contamination from industrial and urban wastewater. Factor analysis made it
      possible to identify ions that would characterize natural processes involving the
      acquisition of salts (HCO3 (-), Na(+), Mg(2+), and Si), as well as anthropic
      activities (SO4 (2-), NO3 (-), Cl(-), Ca(2+), and K(+)).

PMID- 24590227
TI  - Evolution of transcription factor binding in metazoans - mechanisms and
      functional implications.
AB  - Differences in transcription factor binding can contribute to organismal
      evolution by altering downstream gene expression programmes. Genome-wide studies
      in Drosophila melanogaster and mammals have revealed common quantitative and
      combinatorial properties of in vivo DNA binding, as well as marked differences in
      the rate and mechanisms of evolution of transcription factor binding in
      metazoans. Here, we review the recently discovered rapid 're-wiring' of in vivo
      transcription factor binding between related metazoan species and summarize
      general principles underlying the observed patterns of evolution. We then
      consider what might explain the differences in genome evolution between metazoan
      phyla and outline the conceptual and technological challenges facing this
      research field. 

PMID- 24590230
TI  - Effect of seasonal variations on the surface sediment heavy metal enrichment of a
      lake in South India.
AB  - Environmental effects due to continuous accumulation of hazardous materials like
      heavy metals in the surface sediments of lake systems can stress fragile
      ecosystems. Elucidating the mechanisms influencing the concentration and
      distribution of heavy metals becomes vital in formulating lake management
      strategies to preserve the quality of the water environment. Studying of the
      effect of seasonal variations on surface sediments will help in understanding the
      different factors and sources contributing and diluting these persistent
      pollutants. In this study, heavy metal pollution in a tropical shallow lake
      (Akkulam-Veli) in South India was investigated by monitoring the seasonal
      variations of heavy metals and major elements in surface sediments. The metallic
      pollutants (Cr, Ni, Co, Cu, Zn, Pb, Fe, and Mn) and major elements (Si, Ti, Al,
      Ca, Mg, Na, K, and P (measured as oxides) in the surface sediments of this lake
      were monitored during four consecutive seasons. The results were subjected to
      correlation analysis and principal component analysis to study the
      interrelationships of different parameters as well to determine the possible
      origin of pollutants. Although metal concentrations were found to be unaffected
      by seasonal variations, the factors contributing to occurrence of these heavy
      metals were found to be affected by seasonal fluctuations. 

PMID- 24590231
TI  - Application of cold-induced aggregation microextraction as a fast, simple, and
      organic solvent-free method for the separation and preconcentration of Se(IV) in
      rice and various water samples.
AB  - The developed method is based on cold-induced aggregation microextraction of
      Se(IV) using the 1-butyl-3-methylimidazolium hexafluorophosphate ionic liquid as
      an extractant followed by spectrophotometry determination. The extraction of
      Se(IV) was performed in the presence of dithizone as the complexing agent. In
      this method, a very small amount of 1-butyl-3-methylimidazolium
      hexafluorophosphate was added to the sample solution containing Se-dithizone
      complex. Then, the solution was kept in a thermostated bath at 50  degrees C for
      4 min. Subsequently, the solution was cooled in an ice bath and a cloudy solution
      was formed. After centrifuging, the extractant phase was analyzed using a
      spectrophotometric detection method. Some important parameters that might affect
      the extraction efficiency were optimized (HCl, 0.6 mol L(-1); dithizone, 4.0 *
      10(-6) mol L(-1); ionic liquid, 100 MUL). Under the optimum conditions, good
      linear relationship, sensitivity, and reproducibility were obtained. The limit of
      detection (LOD) (3Sb/m) was 1.5 MUg L(-1), and the relative standard deviation
      (RSD) was 1.2 % for 30 MUg L(-1) of Se(IV). The linear range was obtained in the
      range of 5-60 MUg L(-1). It was satisfactory to analyze rice and various water
      samples. 

PMID- 24590233
TI  - Aniline-terminated DNA catalyzes rapid DNA-hydrazone formation at physiological
      pH.
AB  - We report the effect of DNA-templation on aniline-catalyzed N-acylhydrazone
      formation. The reaction occurs in both two-component and three-component systems.
      Through systematic catalyst modifications, we are able to increase the efficiency
      of the DNA-templated variant to 85-fold above that of the uncatalyzed reaction at
      physiological pH. 

PMID- 24590232
TI  - Effects of selected metal oxide nanoparticles on Artemia salina larvae:
      evaluation of mortality and behavioural and biochemical responses.
AB  - The aim was to investigate the toxicity of selected metal oxide nanoparticles (MO
      NPs) on the brine shrimp Artemia salina, by evaluating mortality and behavioural
      and biochemical responses. Larvae were exposed to tin(IV) oxide (stannic oxide
      (SnO2)), cerium(IV) oxide (CeO2) and iron(II, III) oxide (Fe3O4) NPs for 48 h in
      seawater, with MO-NP suspensions from 0.01 to 1.0 mg/mL. Mortality and
      behavioural responses (swimming speed alteration) and enzymatic activities of
      cholinesterase, glutathione-S-transferase and catalase were evaluated. Although
      the MO-NPs did not induce any mortality of the larvae, they caused changes in
      behavioural and biochemical responses. Swimming speed significantly decreased in
      larvae exposed to CeO2 NPs. Cholinesterase and glutathione-S-transferase
      activities were significantly inhibited in larvae exposed to SnO2 NPs, whereas
      cholinesterase activity significantly increased after CeO2 NP and Fe3O4 NP
      exposure. Catalase activity significantly increased in larvae exposed to Fe3O4
      NPs. In conclusion, swimming alteration and cholinesterase activity represent
      valid endpoints for MO-NP exposure, while glutathione-S-transferase and catalase
      activities appear to be NP-specific. 

PMID- 24590234
TI  - A novel biphasic leaching approach for the recovery of Cu and Zn from
      polymetallic bulk concentrate.
AB  - In scale-up biphasic leaching process of polymetallic concentrate, the ferric
      bioregeneration cycles were performed in 15.0L down flow packed bed reactor;
      whereas the chemical leaching cycles were done using the biogenerated ferric in
      an indigenously designed 10.0L stirred tank reactor. The consortium took 25cycles
      for proper biofilm formation. It showed highest iron oxidation rate (IOR) of
      3908.21mg/L/h at 25thcycle under no polymetallic stress. Even under stressed
      conditions, it was 2650-558mg/L/h. Cu extractions were 86.63-46.51 and Zn
      extractions were 67.89-14.74% in 1st-4thcycle, respectively. The developed
      consortium exhibited 17-51times higher IOR compared to original wild type
      consortium. Extraction isotherm for zinc with 30% Cyanex(r) 301 indicated that a
      total of two stages are required for its complete extraction using the phase
      ratio of 2:1 at equilibrium pH 1.5, leaving behind Fe(II) in the raffinate. 

PMID- 24590235
TI  - Genomic variation in Helianthus: learning from the past and looking to the
      future.
AB  - Helianthus is an economically important and genetically diverse genus, containing
      both evolutionary model species and cultivated species. Genetic variation within
      this genus has been examined at many different scales, from genome size changes
      to chromosomal structure to nucleotide variation. The growing amount of genomic
      resources within the genus has yielded insights into the importance of
      paleopolyploid events, and how transposable elements can cause rapid genome size
      increases. The rapidly evolving chromosomes in Helianthus have provided a system
      whereby it has been possible to study how chromosomal rearrangements impact
      speciation, adaptation and introgression. Population and quantitative genetic
      studies have used the abundant nucleotide variation to identify a number of
      candidate genes which may be involved in both local adaptation and domestication.
      The results from these investigations have provided basic knowledge about
      evolution and how to utilize genetic resources for both agriculture and
      conservation. Targeting Helianthus for further study as new technologies emerge
      will allow for a better understanding of how different types of genomic variation
      interact and contribute to phenotypic variation in a complex system that is
      ecologically and economically significant. 

PMID- 24590237
TI  - Efficiency limitations in a low band-gap diketopyrrolopyrrole-based polymer solar
      cell.
AB  - We report the performance and photophysics of a low band-gap diketopyrrolopyrrole
      based copolymer used in bulk heterojunction devices in combination with PC71BM.
      We show that the short lifetime of photogenerated excitons in the polymer
      constitutes an obstacle towards device efficiency by limiting the diffusion range
      of the exciton to the donor-acceptor heterojunction. We employ ultrafast
      transient-probe and fluorescence spectroscopy techniques to examine the excited
      state loss channels inside the devices. We use the high boiling point solvent
      additive 1,8-diiodooctane (DIO) to study the photoexcited state losses in
      different blend morphologies. The solvent additive acts as a compatibiliser
      between the donor and the acceptor material and leads to smaller domain sizes,
      higher charge formation yields and increased device efficiency. 

PMID- 24590236
TI  - The effect of multivitamin/mineral supplements on age-related cataracts: a
      systematic review and meta-analysis.
AB  - Antioxidant vitamins supplements have been suggested as a strategy to decrease
      the risk of age-related cataract development. However, the results from
      observational studies and interventional trials of associations between
      antioxidant vitamins A, C, and E and cataract development have been inconsistent.
      We aim to evaluate the effectiveness of multivitamin/mineral supplements for
      decreasing the risk of age-related cataracts by conducting a systematic review
      and meta-analysis. In September 2013, we searched multiple databases to identify
      relevant studies including both cohort studies and randomized controlled trials
      (RCTs). A random-effects model was used to calculate the pooled relative risks
      (RR) with a 95% confidence interval (CI). Twelve prospective cohort studies and
      two RCTs were included. Pooled results from the cohort studies indicated that
      multivitamin/mineral supplements have a significant beneficial effect in
      decreasing the risk of nuclear cataracts (RR: 0.73; 95% CI: 0.64-0.82), cortical
      cataracts (RR: 0.81; 95% CI: 0.68-0.94), and any cataracts (RR: 0.66; 95% CI:
      0.39-0.93). In addition, there were no decreases in the risk of posterior
      capsular cataracts (RR: 0.96; 95% CI: 0.72-1.20) or cataract surgery (RR: 1.00;
      95% CI: 0.92-1.08). The two RCTs demonstrated that multivitamin/mineral
      supplements could decrease the risk of nuclear cataracts. There is sufficient
      evidence to support the role of dietary multivitamin/mineral supplements for the
      decreasing the risk of age-related cataracts. 

PMID- 24590238
TI  - Angular first-order reversal curves: an advanced method to extract magnetization
      reversal mechanisms and quantify magnetostatic interactions.
AB  - The magnetic properties of ordered hexagonal arrays of Co nanowires (NWs) and
      nanotubes (NTs) with diameters of 50 nm and interwire/tube distances of 105 nm
      were studied using first-order reversal curves (FORCs). We report an advanced
      analysis of angle dependent first-order reversal curves (AFORCs), measured by
      changing the angle of the applied magnetic field from theta = 0 degrees 
      (parallel to the wire/tube axis) to 90 degrees  (perpendicular). This method
      allowed us to determine the magnetization reversal mode and to retrieve
      quantitative information on the magnetostatic interactions between NWs and
      between NTs. In particular, we found a sharp increase in the coercivity
      distribution of the NT arrays for theta > 70 degrees , which is attributed to a
      transition between vortex and transverse reversal modes. Local magnetic
      interactions are found to prevail in the Co NT arrays, steadily increasing from
      theta = 0 degrees  to 90 degrees . However, in the Co NW arrays the mean magnetic
      interactions decrease as theta increases, going from ones similar to local
      interactions to ones smaller than them. 

PMID- 24590239
TI  - What does it take for primary care practices to truly deliver behavioral health
      care?

PMID- 24590240
TI  - Characterization of a beta-1,4-mannanase from a newly isolated strain of Pholiota
      adiposa and its application for biomass pretreatment.
AB  - A highly efficient beta-1,4-mannanase-secreting strain, Pholiota adiposa SKU0714,
      was isolated and identified on the basis of its morphological features and
      sequence analysis of internal transcribed spacer rDNA. P. adiposa beta-1,4
      mannanase was purified to homogeneity from P. adiposa culture supernatants by one
      step chromatography on a Sephacryl gel filtration column. P. adiposa beta-1,4
      mannanase showed the highest activity toward locust bean gum (V max = 1,990 U/mg
      protein, K m = 0.12 mg/mL) ever reported. Its internal amino acid sequence showed
      homology with hydrolases from the glycoside hydrolase family 5 (GH5), indicating
      that the enzyme is a member of the GH5 family. The saccharification of commercial
      mannanase and P. adiposa beta-1,4-mannanase-pretreated rice straw by Celluclast
      1.5L (Novozymes) was compared. In comparison with the commercial Novo
      Mannaway((r)) (113 mg/g-substrate), P. adiposa beta-1,4-mannanase-pretreated rice
      straw released more reducing sugars (141 mg/g-substrate). These properties make
      P. adiposa beta-1,4-mannanase a good candidate as a new commercial beta-1,4
      mannanase to improve biomass pretreatment. 

PMID- 24590241
TI  - Optical coherence tomography provides images similar to histology and allows the
      performance of extensive measurements of drug-eluting metal stents in animal
      ureters.
AB  - Optical coherence tomography (OCT) images and histology images of metal stents
      (MSs) inserted in animal ureters were compared, and the reliability of an OCT
      based automated method for the performance of quantitative evaluation of ureteral
      MSs was evaluated. A zotarolimus-eluting metal stent (ZES) and a bare metal stent
      (BMS) were inserted in each ureter of ten pigs and six rabbits. OCT was performed
      in unobstructed stented ureters. Histopathologic examination of the stented
      ureters embedded in glycol-methacrylate took place. Quadrants of OCT images were
      compared to their respective histologic images by employing two independent
      observers who delineated different layers in the quadrants of OCT images and
      correlated them to the respective histologic quadrants. Manual (integrated OCT
      device software) and automated measurements of the OCT images using an automated
      strut detection method were compared. The observers highly agreed on the
      delineation of urothelium from the lamina propria and the lamina propria from the
      muscle layer of the ureteral wall. The algorithm measurements were similar to the
      manual measurements, and the algorithm proved to be reliable in the evaluation of
      ureteral MSs. Significantly higher endothelial hyperplasia of the BMSs in
      comparison to the ZESs was also quantitatively demonstrated by the strut
      detection method. OCT proved to be a reliable method for the evaluation of
      ureteral MSs. OCT provided images of the stented ureteral lumen similar to light
      microscopy quality. Measurements of the stented ureter are reliably performed by
      the automated strut detection method. 

PMID- 24590242
TI  - Laser therapy and photosensitive medication: a review of the evidence.
AB  - In the 2009 guidelines from the BMLA, the use of non-essential aesthetic lasers
      was contraindicated in patients receiving medication that causes whole-body
      photosensitisation as well as those causing local light sensitisation. Following
      this and anecdotal advice, many laser centres refuse to treat patients who are on
      known photosensitive medication. Therefore, specific patient cohorts that would
      benefit from laser therapy are being denied because of medications, such as long
      term antibiotics for chronic facial acne. This article reviews the published
      literature on lasers and photosensitive medications, the mechanisms of
      photosensitivity and the role of laser in its production. The aim is to analyse
      the available evidence regarding adverse reactions to laser treatment related to
      photosensitive medication. A PubMed review of published article titles and
      abstracts was performed using the search term Laser with each of the following
      terms individually: photosensitive, photosensitiser, photosensitizer,
      phototoxicity, photoallergy, complications, case-report, tetracycline,
      minocycline, amiodarone, nitrofurantoin and medication. Four publications were
      identified, none of which reported any complication in the use of laser in
      patients taking photosensitising medication. As there are no published accounts
      of adverse effects of laser in patients with photosensitive medication, we
      performed a review of the mechanism of photosensitivity by compiling a list of
      photosensitive medication and the peak wavelength of radiation required to
      activate the drug. We recommend a national database of drugs and the wavelengths
      causing photosensitive reactions of each which a laser department can access
      prior to treatment. 

PMID- 24590243
TI  - In search of a new paradigm for protective immunity to TB.
AB  - Clinical trials of vaccines against Mycobacterium tuberculosis are well under way
      and results are starting to come in. Some of these results are not so
      encouraging, as exemplified by the latest Aeras-422 and MVA85A trials. Other than
      empirically determining whether a vaccine reduces the number of cases of active
      tuberculosis, which is a daunting prospect given the chronic nature of the
      disease, we have no way of assessing vaccine efficacy. Therefore, investigators
      seek to identify biomarkers that predict vaccine efficacy. Historically, focus
      has been on the production of interferon-gamma by CD4(+) T cells, but this has
      not been a useful correlate of vaccine-induced protection. In this Opinion
      article, we discuss recent advances in our understanding of the immune control of
      M. tuberculosis and how this knowledge could be used for vaccine design and
      evaluation.

PMID- 24590246
TI  - Incessant formation of chain-like mesoporous silica with a superior binding
      capacity for mercury.
AB  - A novel incessant formation of chain like mesoporous silica (ICMS) has been
      easily materialized using a mixed surfactant (Pluronic P123 and FC-4) as a
      structuring reagent in conjunction with a thiol precursor (3-MPS) through a one
      pot synthetic method. A particular thiol concentration facilitated the
      interaction of the micelle head groups to form long-chain micelles, where FC-4
      enhanced further growth. The rapid interactions of the micelles and the
      condensation of silicic acid and its oligomeric derivatives by coordinating 3-MPS
      through hydrogen bonding interactions leads to form ICMS. The characterization
      results for the ICMS illustrated that it has an ordered hexagonal pore geometry.
      The capability of the ICMS for Hg(2+) adsorption was extensively studied under
      different optimal parameters and the adsorption isothermal values clearly fit
      with the Langmuir and Freundlich isothermal plots. This novel material exhibited
      an unprecedentedly high binding affinity toward even microgram levels of mercury
      ions in wastewater, compared to other thiol-based mesoporous silica. 

PMID- 24590244
TI  - The co-pathogenesis of influenza viruses with bacteria in the lung.
AB  - Concern that a highly pathogenic virus might cause the next influenza pandemic
      has spurred recent research into influenza and its complications. Bacterial
      superinfection in the lungs of people suffering from influenza is a key element
      that promotes severe disease and mortality. This co-pathogenesis is characterized
      by complex interactions between co-infecting pathogens and the host, leading to
      the disruption of physical barriers, dysregulation of immune responses and delays
      in a return to homeostasis. The net effect of this cascade can be the outgrowth
      of the pathogens, immune-mediated pathology and increased morbidity. In this
      Review, advances in our understanding of the underlying mechanisms are discussed,
      and the key questions that will drive the field forwards are articulated. 

PMID- 24590245
TI  - Explaining microbial genomic diversity in light of evolutionary ecology.
AB  - Comparisons of closely related microorganisms have shown that individual genomes
      can be highly diverse in terms of gene content. In this Review, we discuss
      several studies showing that much of this variation is associated with social and
      ecological interactions, which have an important role in the population biology
      of wild populations of bacteria and archaea. These interactions create frequency
      dependent selective pressures that can either stabilize gene frequencies at
      intermediate levels in populations or promote fast gene turnover, which presents
      as low gene frequencies in genome surveys. Thus, interpretation of gene-content
      diversity requires the delineation of populations according to cohesive gene flow
      and ecology, as micro-evolutionary changes arise in response to local selection
      pressures and population dynamics. 

PMID- 24590247
TI  - Giant axonal neuropathy: a clinicoradiopathologic diagnosis.

PMID- 24590248
TI  - The Workforce Task Force Report: clinical implications for neurology.

PMID- 24590249
TI  - Teaching neuroimages: snake eyes appearance in MRI in patient with ALS.

PMID- 24590251
TI  - Pearls & Oy-sters: clues to the diagnosis of adult-onset acid maltase deficiency.

PMID- 24590252
TI  - Journal Club: comparison of symptomatic and asymptomatic persons with Alzheimer
      disease neuropathology.

PMID- 24590253
TI  - Teaching NeuroImages: median nerve MRI changes over time in neuralgic amyotrophy.

PMID- 24590255
TI  - Refractures following removal of plates and elastic nails from paediatric
      forearms.
AB  - We assessed the risk for refractures following removal of elastic nails and
      plates from paediatric forearms. Out of 82 children who had 112 plates removed,
      seven patients (8.5%) had refractures when removals were within 12 months of
      implantation. Those aged 12 years or older were at risk. Out of 24 patients who
      had 38 nails removed, four patients (16.7%) had refractures and the risk was high
      when nails were removed within 6 months of insertion. Children aged 9 years or
      older were at risk. We do not recommend removal of forearm plates within 12
      months and nails within 6 months of implantation. 

PMID- 24590256
TI  - Percutaneous corrective osteotomy for Kirner's deformity: a case report.
AB  - Kirner's deformity is a rare skeletal deformity first described in Germany in
      1927. It is characterized by progressive palmar-radial curvature of the distal
      phalanx of the small finger. Here, we present the case of a 15-year-old boy with
      Kirner's deformity in both little fingers, who was treated with percutaneous
      corrective osteotomy. This was followed by a successful outcome after 36 months. 

PMID- 24590257
TI  - Three-Year long-term outcome of 458 naturalistically treated inpatients with
      major depressive episode: severe relapse rates and risk factors.
AB  - In randomized controlled trials, maintenance treatment for relapse prevention has
      been proven to be efficacious in patients responding in acute treatment, its
      efficacy in long-term outcome in "real-world patients" has yet to be proven.
      Three-year long-term data from a large naturalistic multisite follow-up were
      presented. Severe relapse was defined as suicide, severe suicide attempt, or
      rehospitalization. Next to relapse rates, possible risk factors including
      antidepressant medication were identified using univariate generalized log-rank
      tests and multivariate Cox proportional hazards model for time to severe relapse.
      Overall data of 458 patients were available for analysis. Of all patients, 155
      (33.6%) experienced at least one severe relapse during the 3-year follow-up. The
      following variables were associated with a shorter time to a severe relapse in
      univariate and multivariate analyses: multiple hospitalizations, presence of
      avoidant personality disorder, continuing antipsychotic medication, and no
      further antidepressant treatment. In comparison with other studies, the observed
      rate of severe relapse during 3-year period is rather low. This is one of the
      first reports demonstrating a beneficial effect of long-term antidepressant
      medication on severe relapse rates in naturalistic patients. Concomitant
      antipsychotic medication may be a proxy marker for treatment resistant and
      psychotic depression.

PMID- 24590259
TI  - Allocating operating room block time using historical caseload variability.
AB  - Operating room (OR) allocation and planning is one of the most important
      strategic decisions that OR managers face. The number of ORs that a hospital
      opens depends on the number of blocks that are allocated to the surgical groups,
      services, or individual surgeons, combined with the amount of open posting time
      (i.e., first come, first serve posting) that the hospital wants to provide. By
      allocating too few ORs, a hospital may turn away surgery demand whereas opening
      too many ORs could prove to be a costly decision. The traditional method of
      determining block frequency and size considers the average historical surgery
      demand for each group. However, given that there are penalties to the system for
      having too much or too little OR time allocated to a group, demand variability
      should play a role in determining the real OR requirement. In this paper we
      present an algorithm that allocates block time based on this demand variability,
      specifically accounting for both over-utilized time (time used beyond the block)
      and under-utilized time (time unused within the block). This algorithm provides a
      solution to the situation in which total caseload demand can be accommodated by
      the total OR resource set, in other words not in a capacity-constrained
      situation. We have found this scenario to be common among several regional
      healthcare providers with large OR suites and excess capacity. This algorithm
      could be used to adjust existing blocks or to assign new blocks to surgeons that
      did not previously have a block. We also have studied the effect of turnover time
      on the number of ORs that needs to be allocated. Numerical experiments based on
      real data from a large health-care provider indicate the opportunity to achieve
      over 2,900 hours of OR time savings through improved block allocations. 

PMID- 24590258
TI  - The purine riboswitch as a model system for exploring RNA biology and chemistry.
AB  - Over the past decade the purine riboswitch, and in particular its nucleobase
      binding aptamer domain, has emerged as an important model system for exploring
      various aspects of RNA structure and function. Its relatively small size,
      structural simplicity and readily observable activity enable application of a
      wide variety of experimental approaches towards the study of this RNA. These
      analyses have yielded important insights into small molecule recognition, co
      transcriptional folding and secondary structural switching, and conformational
      dynamics that serve as a paradigm for other RNAs. In this article, the current
      state of understanding of the purine riboswitch family and how this growing
      knowledge base is starting to be exploited in the creation of novel RNA devices
      are examined. This article is part of a Special Issue entitled: Riboswitches.

PMID- 24590262
TI  - Computational analysis of dynamic interaction of two red blood cells in a
      capillary.
AB  - The dynamic interaction of two red blood cells (RBCs) in a capillary is
      investigated computationally by the two-fluid model, including their deformable
      motion and interaction. For characterization of the deformation, the RBC membrane
      is treated as a curved two-dimensional shell with finite thickness by the shell
      model, and allowed to undergo the stretching strain and bending deformation.
      Moreover, a Morse potential is adopted to model the intercellular interaction for
      the aggregation behavior, which is characterized as the weak attraction at far
      distance and strong repulsion at near distance. For validation of the present
      technique, the dynamic interaction of two RBCs in static blood plasma is
      simulated firstly, where the RBCs aggregate slowly until a balanced configuration
      is achieved between the deformation and aggregation forces. The balanced
      configuration is in good agreement with the results reported previously. Three
      important effects on the dynamic behavior of RBCs are then analyzed, and they are
      the initial RBC shape, RBC deformability, and the intercellular interaction
      strength. It is found that the RBC is less deformed into a well-known parachute
      shape when the initial RBC shape is larger. Similarly, if the elastic shear
      modulus and bending stiffness of RBC membrane increase, the RBC resistance to
      deformation becomes higher, such that the RBC is less deformed. The simulation
      results also demonstrate that the RBC deformability strongly depends on the
      intercellular interaction strength. The RBCs deform more easily as the
      intercellular interaction strength increases. 

PMID- 24590261
TI  - Icariin enhances radiosensitivity of colorectal cancer cells by suppressing NF
      kappaB activity.
AB  - Radiation therapy is an integral part of the current therapeutic protocols in
      colorectal cancer. However, only a small proportion of the patients achieved
      complete pathological response because of the treatment-induced resistance to
      radiation. Previous studies have shown that radioresistance is associated with NF
      kappaB activation and that suppression of NF-kappaB could potentiate the response
      of colorectal cancer cells to radiotherapy. Icariin, a natural flavonoid, has
      been shown to suppress NF-kappaB activity. The present study was carried out to
      investigate whether icariin could act as a radiosensitizer in colorectal cancer
      cells and murine model of the colorectal cancer. We also sought to understand the
      mechanisms underlying the icariin-mediated radiosensitization. Our results showed
      that icariin enhanced the radiation-mediated anti-proliferative effect both in
      vitro and in vivo. Further, icariin exerted the anti-proliferative and/or pro
      apoptotic effect possibly, by: (1) inducing the cell arrest in G2/M phases of the
      cell cycle, or by (2) downregulating NF-kappaB and the anti-apoptotic gene
      products monitored by this transcription factor. Icariin could also potentiate
      the efficacy of radiotherapy in the murine model of colorectal cancer. Taken
      together, these results suggest that the use of icariin may provide with a new
      approach for sensitizing the radiotherapy in colorectal cancer. 

PMID- 24590260
TI  - Overcoming the cutaneous barrier with microemulsions.
AB  - Microemulsions are fluid and isotropic formulations that have been widely studied
      as delivery systems for a variety of routes, including the skin. In spite of what
      the name suggests, microemulsions are nanocarriers, and their use as topical
      delivery systems derives from their multiple advantages compared to other
      dermatological formulations, such as ease of preparation, thermodynamic stability
      and penetration-enhancing properties. Composition, charge and internal structure
      have been reported as determinant factors for the modulation of drug release and
      cutaneous and transdermal transport. This manuscript aims at reviewing how these
      and other characteristics affect delivery and make microemulsions appealing for
      topical and transdermal administration, as well as how they can be modulated
      during the formulation design to improve the potential and efficacy of the final
      system. 

PMID- 24590263
TI  - Differential sensitivity of telomerase from human hematopoietic stem cells and
      leukemic cell lines to mild hyperthermia.
AB  - We have investigated the effects of hyperthermia (HT) on cell proliferation and
      telomerase activity of human hematopoietic stem cells (HSCs) and compared with
      human leukemic cell lines (TF-1, K562 and HL-60). The cells were exposed to HT at
      42 and 43  degrees C up to 120 min. The cells were incubated at 37  degrees C for
      96 h. Then the cells were collected and assayed for cell proliferation,
      viability, telomerase activity, and terminal restriction fragment (TRF) lengths.
      The enzyme activity from HSCs was decreased up to 68.6 at 42 and 85.1 % at 43 
      degrees C for 120 min. This inhibition in leukemic cells was up to 28.9 and 53.6
      % in TF-1; 53 and 63.9 % in K562; 45.2 and 61.1 % in HL-60 cells. The treated
      cells showed TRF lengths about 5.3 kb for control HL-60 cells, 5.0 kb for HL-60
      cells treated at 42 and 4.5 kb at 43  degrees C for 120 min. In HSCs, the TRF
      length was about 4.5 kb for untreated cells and 4.0-4.5 kb for treated cells at
      42 and 43  degrees C for 120 min. The time response curves indicated that,
      inhibition of the enzyme activity in leukemic cells was dependent to the time of
      exposure to HT. But in HSCs, the inhibition was reached to steady state at 15 min
      exposure to 43  degrees C heat stress. TRF length was constant at treated two
      types of cells, which implies that in cells subjected to mild HT no telomere
      shortening was observed.

PMID- 24590264
TI  - A CO2-responsive surface with an amidine-terminated self-assembled monolayer for
      stimuli-induced selective adsorption.
AB  - A specific bifunctional molecule containing amidine is prepared to construct a
      CO2-responsive surface via molecular self-assembly. The smart surface undergoes
      CO2-responsive switching of surface charges and wettability, leading to
      distinctively selective adsorption of hydrophobic/hydrophilic molecules. 

PMID- 24590265
TI  - No association between XRCC1 gene Arg194Trp polymorphism and risk of lung cancer:
      evidence based on an updated cumulative meta-analysis.
AB  - X-ray repair cross-complementing group 1 (XRCC1) gene Arg194Trp polymorphism has
      been reported to be associated with risk of lung cancer in many published
      studies. Nevertheless, the research results were inconclusive and conflicting. To
      reach conclusive results, several meta-analysis studies were conducted by
      combining results from literature reports through pooling analysis. However,
      these previous meta-analysis studies were still not consistent. Hence, we used an
      updated and cumulative meta-analysis to get a more comprehensive and precise
      result from 25 case-control studies searching through the PubMed database up to
      September 1, 2013. The meta-analysis was carried out by the Comprehensive Meta
      Analysis software and the odds ratio (OR) with 95 % confidence interval (CI) was
      used to estimate the pooled effect. The result involving 8,876 lung cancer
      patients and 11,210 controls revealed that XRCC1 Arg194Trp polymorphism was not
      associated with lung cancer risk [(OR=0.97, 95 %CI=0.92-1.03) for Trp vs. Arg;
      (OR=0.92, 95 % CI=0.85-0.98) for ArgTrp vs. ArgArg; (OR=1.07, 95 % CI=0.92-1.23)
      for TrpTrp vs. ArgArg; (OR=0.93, 95 % CI=0.87-1.00) for (TrpTrp + ArgTrp) vs.
      ArgArg; and (OR=1.08, 95 % CI=0.94-1.25) for TrpTrp vs. (ArgTrp + ArgArg)]. The
      cumulative meta-analysis showed that the results maintained the same, while the
      ORs with 95 % CI were more stable with the accumulation of case-control studies.
      The sensitivity and subgroups analyses showed that the results were robust and
      not affected by any single study with no publication bias. Relevant studies might
      not be needed for supporting these results.

PMID- 24590266
TI  - XRCC1 and XPD genetic polymorphisms and clinical outcomes of gastric cancer
      patients treated with oxaliplatin-based chemotherapy: a meta-analysis.
AB  - This meta-analysis aimed to obtain a comprehensive and reliable assessment of the
      relationships between XRCC1 Arg399Gln and XPD Lys751Gln polymorphisms and the
      clinical outcomes of gastric cancer (GC) patients treated with oxaliplatin-based
      chemotherapy. The PubMed, CINAHL, Web of Science, CISCOM, EBSCO, Google Scholar,
      Cochrane Library, and CBM databases were searched for relevant articles published
      before September 1, 2013 without language restrictions. Crude odd ratios (ORs) or
      hazard risk (HR) [95 % confidence intervals (CI)] were calculated. Twelve
      clinical cohort studies were assessed with a total 1,024 GC patients treated with
      oxaliplatin-based chemotherapy. Our meta-analysis findings revealed that GC
      patients with the GA+AA (A carrier) genotypes of XRCC1 Arg399Gln showed a lower
      effective clinical response (CR+PR) than those with the GG (A non-carrier)
      genotype (OR=0.41, 95 % CI 0.20~0.82, P=0.012). However, there was no
      statistically significant difference in effective clinical response between those
      with XPD AC+CC (C carrier) genotypes and CC (C non-carrier) genotype (OR=0.55, 95
      % CI 0.28~1.07, P=0.076). Furthermore, the GA+AA genotypes of XRCC1 Arg399Gln was
      associated with a worse progression-free survival (PFS) and overall survival (OS)
      compared with the CC genotype (PFS, HR=1.90, 95 % CI 1.12~2.69, P<0.001; OS,
      HR=2.13, 95 % CI 0.79~3.47, P=0.002, respectively). No relationships were found
      between XPD Lys751Gln polymorphism and both PFS and OS (all P>0.05). No
      publication bias was detected in this meta-analysis. Results from the current
      meta-analysis indicate that XRCC1 Arg399Gln polymorphism may be associated with
      poor clinical outcomes in GC patients treated with oxaliplatin-based
      chemotherapy.

PMID- 24590267
TI  - High sensitivity of touch imprint cytology in young patients with invasive
      lobular carcinoma of the breast.
AB  - Invasive lobular carcinoma (ILC) of the breast is a rare type of breast cancer.
      Metastatic ILC is difficult to identify in sentinel lymph nodes (SLNs) because of
      its low-grade cytomorphology and its tendency to resemble lymphocytes. Touch
      imprint cytology (TIC) is a rapid method for evaluating SLNs intraoperatively. We
      sought to evaluate this technique in the identification of SLN metastases in ILC.
      A total of 230 SLNs from 88 patients diagnosed with ILC were examined with TIC,
      and the results were compared with their histological diagnosis. We first
      confirmed some typical cytological features of SLN metastases in ILC such as a
      thick eosinophilic background and hyperplasia of small cell lacking adhesion.
      Further analysis showed that sensitivity of TIC was 60.5 % on per-node basis and
      58.3 % on per-patient basis; specificity of TIC was 100 % on per-node basis and
      100 % on per-patient basis. Interestingly, when we divided patients according to
      their ages, the sensitivity of TIC in patients younger than 50 years old greatly
      increased to 90.9 % on per-node basis and 85.7 % on per-patient basis, whereas
      the specificity remained 100 % on both per-node basis and per-patient basis.
      However, different tumor sizes did not clearly change the sensitivity of TIC
      compared to the overall sensitivity. Patients with tumor size bigger than 1 cm
      revealed a TIC sensitivity of 59.4 % on per-node basis and 55.0 % on per-patient
      basis. These results suggest that TIC can be used as a reliable method of
      detecting SLN metastasis only in young patients with ILC.

PMID- 24590268
TI  - Increased lung cancer risk associated with the TERT rs2736100 polymorphism: an
      updated meta-analysis.
AB  - The rs2736100 polymorphism in the telomerase reverse transcriptase (TERT) gene
      has been implicated in lung cancer risk in multiple populations, but the existing
      evidence lacks statistical power to draw a convincing conclusion. Therefore, the
      present study was devised to derive a more precise estimation of the association
      between rs2736100 and lung cancer risk. The PubMed, Embase, and Web of Science
      databases were comprehensively searched for papers concerning lung cancer risk in
      relation to rs2736100. Pooled odds ratios (ORs) and the 95 % confidence intervals
      (CIs) were appropriately calculated using the fixed or random effects model. Meta
      analysis of 20 independent studies involving 39,715 cancer cases and 61,462
      control subjects showed statistical evidence for an association between rs2736100
      and increased risk of lung cancer. Subgroup analysis by ethnicity demonstrated a
      significant association among both Asian and Caucasian populations. We
      additionally found an increased risk of non-small cell lung cancer and lung
      adenocarcinoma strongly associated with rs2736100. These data provide further
      evidence supporting a role for genetic susceptibility of TERT rs2736100 in the
      development of lung cancer.

PMID- 24590269
TI  - Correlation of TNFAIP8 overexpression with the proliferation, metastasis, and
      disease-free survival in endometrial cancer.
AB  - Tumor necrosis factor alpha-induced protein 8 (TNFAIP8) is an apoptosis regulator
      proven to have an important function in the proliferation, invasion, metastasis,
      and progression of malignancies. In this study, we investigated the clinical role
      of TNFAIP8 overexpression in endometrial cancer (EC) and determined the
      relationship of TNFAIP8 with the proliferative antigen Ki-67 and metastasis
      related gene matrix metallopeptidase 9 (MMP9) in 225 tumor specimens by
      immunohistochemistry and western blot, in order to elucidate more information on
      the role of TNFAIP8 protein with regard to the pathogenesis of EC. An association
      was observed between TNFAIP8 overexpression and clinicopathologic factors, such
      as advanced International Federation of Gynecology and Obstetrics stage
      (P<0.001), higher histologic grade (P=0.017), deep myometrial invasion (P=0.030),
      lymphovascular space invasion (P=0.011), lymph node metastasis (P<0.001), and
      recurrence. Furthermore, TNFAIP8 overexpression was strongly correlated with MMP9
      and Ki-67 expression in the progression of ECs. Patients with high expression of
      TNFAIP8 (P<0.001 for both) and Ki-67 (P=0.007 and P=0.008) had poor overall
      survival and disease-free survival (DFS) rates. MMP9 overexpression did not
      affect survival outcomes (P>0.05). Multivariate Cox regression analysis revealed
      that TNFAIP8 (P=0.029) and lymph node metastasis (P=0.022) were independent
      factors of DFS in patients with EC. These findings suggested that TNFAIP8 may be
      used as a prognostic marker for the recurrence of EC, and its promotion of the
      proliferation and metastasis in EC may be due to its mediation of Ki-67 and MMP9.

PMID- 24590270
TI  - Quantitative metabolome analysis profiles activation of glutaminolysis in glioma
      with IDH1 mutation.
AB  - Isocitrate dehydrogenase 1 (IDH1), which localizes to the cytosol and
      peroxisomes, catalyzes the oxidative decarboxylation of isocitrate to alpha
      ketoglutarate (alpha-KG) and in parallel converts NADP(+) to NADPH. IDH1
      mutations are frequently detected in grades 2-4 gliomas and in acute myeloid
      leukemias (AML). Mutations of IDH1 have been identified at codon 132, with
      arginine being replaced with histidine in most cases. Mutant IDH1 gains novel
      enzyme activity converting alpha-KG to D-2-hydroxyglutarate (2-HG) which acts as
      a competitive inhibitor of alpha-KG. As a result, the activity of alpha-KG
      dependent enzyme is reduced. Based on these findings, 2-HG has been proposed to
      be an oncometabolite. In this study, we established HEK293 and U87 cells that
      stably expressed IDH1-WT and IDH1-R132H and investigated the effect of
      glutaminase inhibition on cell proliferation with 6-diazo-5-oxo-L-norleucine
      (DON). We found that cell proliferation was suppressed in IDH1-R132H cells. The
      addition of alpha-KG restored cell proliferation. The metabolic features of 33
      gliomas with wild type IDH1 (IDH1-WT) and with IDH1-R132H mutation were examined
      by global metabolome analysis using capillary electrophoresis time-of-flight mass
      spectrometry (CE-TOFMS). We showed that the 2-HG levels were highly elevated in
      gliomas with IDH1-R132H mutation. Intriguingly, in gliomas with IDH1-R132H,
      glutamine and glutamate levels were significantly reduced which implies
      replenishment of alpha-KG by glutaminolysis. Based on these results, we concluded
      that glutaminolysis is activated in gliomas with IDH1-R132H mutation and that
      development of novel therapeutic approaches targeting activated glutaminolysis is
      warranted. 

PMID- 24590271
TI  - The lymphatic vasculature revisited.
AB  - Lymphatic vessels constitute a ubiquitous countercurrent system to the blood
      vasculature that returns interstitial fluid, salts, small molecules, resorbed
      fat, and cells to the bloodstream. They serve as conduits to lymph nodes and are
      essential for multiple physiologic activities. However, they are also hijacked by
      cancer cells to establish initial lymph node metastases, as well as by infectious
      agents and parasites. Despite these obvious important functions in human
      pathologies, a more detailed understanding of the molecular mechanisms involved
      in the regulation of the lymphatic vasculature has trailed that of the blood
      vasculature for many years, mainly because critical specific characteristics of
      lymphatic endothelial cells were discovered only recently. In this Review series,
      several major aspects of the active and passive involvement of the lymphatic
      vasculature in human disease and physiology are presented, with a focus on
      translational findings. 

PMID- 24590272
TI  - Lymphangiogenic factors, mechanisms, and applications.
AB  - Lymphangiogenesis, the growth of lymphatic vessels, is essential in embryonic
      development. In adults, it is involved in many pathological processes such as
      lymphedema, inflammatory diseases, and tumor metastasis. Advances during the past
      decade have dramatically increased the knowledge of the mechanisms of
      lymphangiogenesis, including the roles of transcription factors, lymphangiogenic
      growth factors and their receptors, and intercellular and intracellular signaling
      cascades. Strategies based on these mechanisms are being tested in the treatment
      of various human diseases such as cancer, lymphedema, and tissue allograft
      rejection. This Review summarizes the recent progress on lymphangiogenic
      mechanisms and their applications in disease treatment. 

PMID- 24590273
TI  - Development of the mammalian lymphatic vasculature.
AB  - The two vascular systems of our body are the blood and lymphatic vasculature. Our
      understanding of the cellular and molecular processes controlling the development
      of the lymphatic vasculature has progressed significantly in the last decade. In
      mammals, this is a stepwise process that starts in the embryonic veins, where
      lymphatic EC (LEC) progenitors are initially specified. The differentiation and
      maturation of these progenitors continues as they bud from the veins to produce
      scattered primitive lymph sacs, from which most of the lymphatic vasculature is
      derived. Here, we summarize our current understanding of the key steps leading to
      the formation of a functional lymphatic vasculature. 

PMID- 24590274
TI  - Genetics of lymphatic anomalies.
AB  - Lymphatic anomalies include a variety of developmental and/or functional defects
      affecting the lymphatic vessels: sporadic and familial forms of primary
      lymphedema, secondary lymphedema, chylothorax and chylous ascites, lymphatic
      malformations, and overgrowth syndromes with a lymphatic component. Germline
      mutations have been identified in at least 20 genes that encode proteins acting
      around VEGFR-3 signaling but also downstream of other tyrosine kinase receptors.
      These mutations exert their effects via the RAS/MAPK and the PI3K/AKT pathways
      and explain more than a quarter of the incidence of primary lymphedema, mostly of
      inherited forms. More common forms may also result from multigenic effects or
      post-zygotic mutations. Most of the corresponding murine knockouts are homozygous
      lethal, while heterozygotes are healthy, which suggests differences in human and
      murine physiology and the influence of other factors. 

PMID- 24590275
TI  - Emerging lymphatic imaging technologies for mouse and man.
AB  - The lymphatic circulatory system has diverse functions in lipid absorption, fluid
      homeostasis, and immune surveillance and responds dynamically when presented with
      infection, inflammation, altered hemodynamics, and cancer. Visualization of these
      dynamic processes in human disease and animal models of disease is key to
      understanding the contributory role of the lymphatic circulatory system in
      disease and to devising effective therapeutic strategies. Longitudinal, non
      destructive, and repeated imaging is necessary to expand our understanding of
      disease progression and regression in basic science and clinical investigations.
      Herein we summarize recent advances in in vivo lymphatic imaging employing
      magnetic resonance, computed tomography, lymphoscintigraphy, and emerging optical
      techniques with respect to their contributory roles in both basic science and
      clinical research investigations. 

PMID- 24590276
TI  - New developments in clinical aspects of lymphatic disease.
AB  - The lymphatic system is fundamentally important to cardiovascular disease,
      infection and immunity, cancer, and probably obesity--the four major challenges
      in healthcare in the 21st century. This Review will consider the manner in which
      new knowledge of lymphatic genes and molecular mechanisms has demonstrated that
      lymphatic dysfunction should no longer be considered a passive bystander in
      disease but rather an active player in many pathological processes and,
      therefore, a genuine target for future therapeutic developments. The specific
      roles of the lymphatic system in edema, genetic aspects of primary lymphedema,
      infection (cellulitis/erysipelas), Crohn's disease, obesity, cancer, and cancer
      related lymphedema are highlighted.

PMID- 24590277
TI  - Mechanisms of lymphatic metastasis.
AB  - Malignant tumors release growth factors such as VEGF-C to induce lymphatic vessel
      expansion (lymphangiogenesis) in primary tumors and in draining sentinel LNs,
      thereby promoting LN metastasis. Surprising recent evidence suggests that
      lymphatic vessels do not merely represent passive channels for tumor spread, but
      that they may actively promote tumor cell recruitment to LNs, cancer stem cell
      survival, and immune modulation. New imaging approaches allow the sensitive
      visualization of the earliest LN metastases and the quantitative, noninvasive
      measurement of the function of tumor-draining lymphatic vessels, with potential
      applications in the development of biomarkers for prognosis and measurement of
      therapeutic response. 

PMID- 24590278
TI  - Lymphatic transport of high-density lipoproteins and chylomicrons.
AB  - The life cycles of VLDLs and most LDLs occur within plasma. By contrast, the role
      of HDLs in cholesterol transport from cells requires that they readily gain
      access to and function within interstitial fluid. Studies of lymph derived from
      skin, connective tissue, and adipose tissue have demonstrated that particles as
      large as HDLs require transport through lymphatics to return to the bloodstream
      during reverse cholesterol transport. Targeting HDL for therapeutic purposes will
      require understanding its biology in the extravascular compartment, within the
      interstitium and lymph, in health and disease, and we herein review the processes
      that mediate the transport of HDLs and chylomicrons through the lymphatic
      vasculature. 

PMID- 24590279
TI  - Inflammation-associated lymphangiogenesis: a double-edged sword?
AB  - Lymphangiogenesis and lymphatic vessel remodeling are complex biological
      processes frequently observed during inflammation. Accumulating evidence
      indicates that inflammation-associated lymphangiogenesis (IAL) is not merely an
      endpoint event, but actually a phenomenon actively involved in the
      pathophysiology of various inflammatory disorders. The VEGF-C/VEGFR-3 and VEGF
      A/VEGF-R2 signaling pathways are two of the best-studied pathways in IAL. Methods
      targeting these molecules, such as prolymphangiogenic or antilymphatic
      treatments, were found to be beneficial in various preclinical and/or clinical
      studies. This Review focuses on the most recent achievements in the fields of
      lymphatic biology relevant to inflammatory conditions. Additionally, preclinical
      and clinical therapies that modulate IAL are summarized. 

PMID- 24590280
TI  - Emerging roles of lymphatic endothelium in regulating adaptive immunity.
AB  - Emerging research on the roles of stromal cells in modulating adaptive immune
      responses has included a new focus on lymphatic endothelial cells (LECs). LECs
      are presumably the first cells that come into direct contact with peripheral
      antigens, cytokines, danger signals, and immune cells travelling from peripheral
      tissues to lymph nodes. LECs can modulate dendritic cell function, present
      antigens to T cells on MHC class I and MHC class II molecules, and express
      immunomodulatory cytokines and receptors, which suggests that their roles in
      adaptive immunity are far more extensive than previously realized. This Review
      summarizes the emergent evidence that LECs are important in maintaining
      peripheral tolerance, limiting and resolving effector T cell responses, and
      modulating leukocyte function. 

PMID- 24590281
TI  - Lymphatic vessels and tertiary lymphoid organs.
AB  - Tertiary lymphoid organs (TLOs) are accumulations of lymphoid cells in chronic
      inflammation that resemble LNs in their cellular content and organization, high
      endothelial venules, and lymphatic vessels (LVs). Although acute inflammation can
      result in defective LVs, TLO LVs appear to function normally in that they drain
      fluid and transport cells that respond to chemokines and sphingosine-1-phosphate
      (S1P) gradients. Molecular regulation of TLO LVs differs from lymphangiogenesis
      in ontogeny with a dependence on cytokines and hematopoietic cells. Ongoing work
      to elucidate the function and molecular regulation of LVs in TLOs is providing
      insight into therapies for conditions as diverse as lymphedema, autoimmunity, and
      cancer. 

PMID- 24590284
TI  - Psychometric characteristics of health-related quality-of-life questionnaires in
      oropharyngeal dysphagia.
AB  - Dysphagia can have severe consequences for the patient's health, influencing
      health-related quality of life (HRQoL). Sound psychometric properties of HRQoL
      questionnaires are a precondition for assessing the impact of dysphagia, the
      focus of this study, resulting in recommendations for the appropriate use of
      these questionnaires in both clinical practice and research contexts. We
      performed a systematic review starting with a search for and retrieval of all
      full-text articles on the development of HRQoL questionnaires related to
      oropharyngeal dysphagia and/or their psychometric validation from the electronic
      databases PubMed and Embase published up to June 2011. Psychometric properties
      were judged according to quality criteria proposed for health status
      questionnaires. Eight questionnaires were included in this study. Four are aimed
      solely at HRQoL in oropharyngeal dysphagia: the deglutition handicap index (DHI),
      dysphagia handicap index (DHI'), M.D. Anderson Dysphagia Inventory (MDADI), and
      SWAL-QOL, while the EDGQ, EORTC QLQ-STO 22, EORTC QLQ-OG 25 and EORTC QLQ-H&N35
      focus on other primary diseases resulting in dysphagia. The psychometric
      properties of the DHI, DHI', MDADI, and SWAL-QOL were evaluated. For appropriate
      applicability of HRQoL questionnaires, strong scores on the psychometric criteria
      face validity, criterion validity, and interpretability are prerequisites. The
      SWAL-QOL has the strongest ratings for these criteria, while the DHI' is the most
      easy to apply given its 25 items and the use of a uniform scoring format. For
      optimal use of HRQoL questionnaires in diverse settings, it is necessary to
      combine psychometric and utility approaches. 

PMID- 24590285
TI  - Assembly of the cochlear gap junction macromolecular complex requires connexin
      26.
AB  - Hereditary deafness affects approximately 1 in 2,000 children. Mutations in the
      gene encoding the cochlear gap junction protein connexin 26 (CX26) cause
      prelingual, nonsyndromic deafness and are responsible for as many as 50% of
      hereditary deafness cases in certain populations. Connexin-associated deafness is
      thought to be the result of defective development of auditory sensory epithelium
      due to connexion dysfunction. Surprisingly, CX26 deficiency is not compensated
      for by the closely related connexin CX30, which is abundantly expressed in the
      same cochlear cells. Here, using two mouse models of CX26-associated deafness, we
      demonstrate that disruption of the CX26-dependent gap junction plaque (GJP) is
      the earliest observable change during embryonic development of mice with connexin
      associated deafness. Loss of CX26 resulted in a drastic reduction in the GJP area
      and protein level and was associated with excessive endocytosis with increased
      expression of caveolin 1 and caveolin 2. Furthermore, expression of deafness
      associated CX26 and CX30 in cell culture resulted in visible disruption of GJPs
      and loss of function. Our results demonstrate that deafness-associated mutations
      in CX26 induce the macromolecular degradation of large gap junction complexes
      accompanied by an increase in caveolar structures. 

PMID- 24590286
TI  - SPARC promotes leukemic cell growth and predicts acute myeloid leukemia outcome.
AB  - Aberrant expression of the secreted protein, acidic, cysteine-rich (osteonectin)
      (SPARC) gene, which encodes a matricellular protein that participates in normal
      tissue remodeling, is associated with a variety of diseases including cancer, but
      the contribution of SPARC to malignant growth remains controversial. We
      previously reported that SPARC was among the most upregulated genes in
      cytogenetically normal acute myeloid leukemia (CN-AML) patients with gene
      expression profiles predictive of unfavorable outcome, such as mutations in
      isocitrate dehydrogenase 2 (IDH2-R172) and overexpression of the oncogenes brain
      and acute leukemia, cytoplasmic (BAALC) and v-ets erythroblastosis virus E26
      oncogene homolog (ERG). In contrast, SPARC was downregulated in CN-AML patients
      harboring mutations in nucleophosmin (NPM1) that are associated with favorable
      prognosis. Based on these observations, we hypothesized that SPARC expression is
      clinically relevant in AML. Here, we found that SPARC overexpression is
      associated with adverse outcome in CN-AML patients and promotes aggressive
      leukemia growth in murine models of AML. In leukemia cells, SPARC expression was
      mediated by the SP1/NF-kappaB transactivation complex. Furthermore, secreted
      SPARC activated the integrin-linked kinase/AKT (ILK/AKT) pathway, likely via
      integrin interaction, and subsequent beta-catenin signaling, which is involved in
      leukemia cell self-renewal. Pharmacologic inhibition of the SP1/NF-kappaB complex
      resulted in SPARC downregulation and leukemia growth inhibition. Together, our
      data indicate that evaluation of SPARC expression has prognosticative value and
      SPARC is a potential therapeutic target for AML. 

PMID- 24590287
TI  - Endothelial mitochondrial oxidative stress determines podocyte depletion in
      segmental glomerulosclerosis.
AB  - Focal segmental glomerular sclerosis (FSGS) is a primary kidney disease that is
      commonly associated with proteinuria and progressive loss of glomerular function,
      leading to development of chronic kidney disease (CKD). FSGS is characterized by
      podocyte injury and depletion and collapse of glomerular capillary segments.
      Progression of FSGS is associated with TGF-beta activation in podocytes; however,
      it is not clear how TGF-beta signaling promotes disease. Here, we determined that
      podocyte-specific activation of TGF-beta signaling in transgenic mice and BALB/c
      mice with Adriamycin-induced glomerulosclerosis is associated with endothelin-1
      (EDN1) release by podocytes, which mediates mitochondrial oxidative stress and
      dysfunction in adjacent endothelial cells via paracrine EDN1 receptor type A
      (EDNRA) activation. Endothelial dysfunction promoted podocyte apoptosis, and
      inhibition of EDNRA or scavenging of mitochondrial-targeted ROS prevented
      podocyte loss, albuminuria, glomerulosclerosis, and renal failure. We confirmed
      reciprocal crosstalk between podocytes and endothelial cells in a coculture
      system. Biopsies from patients with FSGS exhibited increased mitochondrial DNA
      damage, consistent with EDNRA-mediated glomerular endothelial mitochondrial
      oxidative stress. Our studies indicate that segmental glomerulosclerosis develops
      as a result of podocyte-endothelial crosstalk mediated by EDN1/EDNRA-dependent
      mitochondrial dysfunction and suggest that targeting the reciprocal interaction
      between podocytes and endothelia may provide opportunities for therapeutic
      intervention in FSGS. 

PMID- 24590288
TI  - Dysregulation of ubiquitin homeostasis and beta-catenin signaling promote spinal
      muscular atrophy.
AB  - The autosomal recessive neurodegenerative disease spinal muscular atrophy (SMA)
      results from low levels of survival motor neuron (SMN) protein; however, it is
      unclear how reduced SMN promotes SMA development. Here, we determined that
      ubiquitin-dependent pathways regulate neuromuscular pathology in SMA. Using mouse
      models of SMA, we observed widespread perturbations in ubiquitin homeostasis,
      including reduced levels of ubiquitin-like modifier activating enzyme 1 (UBA1).
      SMN physically interacted with UBA1 in neurons, and disruption of Uba1 mRNA
      splicing was observed in the spinal cords of SMA mice exhibiting disease
      symptoms. Pharmacological or genetic suppression of UBA1 was sufficient to
      recapitulate an SMA-like neuromuscular pathology in zebrafish, suggesting that
      UBA1 directly contributes to disease pathogenesis. Dysregulation of UBA1 and
      subsequent ubiquitination pathways led to beta-catenin accumulation, and
      pharmacological inhibition of beta-catenin robustly ameliorated neuromuscular
      pathology in zebrafish, Drosophila, and mouse models of SMA. UBA1-associated
      disruption of beta-catenin was restricted to the neuromuscular system in SMA
      mice; therefore, pharmacological inhibition of beta-catenin in these animals
      failed to prevent systemic pathology in peripheral tissues and organs, indicating
      fundamental molecular differences between neuromuscular and systemic SMA
      pathology. Our data indicate that SMA-associated reduction of UBA1 contributes to
      neuromuscular pathogenesis through disruption of ubiquitin homeostasis and
      subsequent beta-catenin signaling, highlighting ubiquitin homeostasis and beta
      catenin as potential therapeutic targets for SMA. 

PMID- 24590289
TI  - Fibrotic extracellular matrix activates a profibrotic positive feedback loop.
AB  - Pathological remodeling of the extracellular matrix (ECM) by fibroblasts leads to
      organ failure. Development of idiopathic pulmonary fibrosis (IPF) is
      characterized by a progressive fibrotic scarring in the lung that ultimately
      leads to asphyxiation; however, the cascade of events that promote IPF are not
      well defined. Here, we examined how the interplay between the ECM and fibroblasts
      affects both the transcriptome and translatome by culturing primary fibroblasts
      generated from IPF patient lung tissue or nonfibrotic lung tissue on
      decellularized lung ECM from either IPF or control patients. Surprisingly, the
      origin of the ECM had a greater impact on gene expression than did cell origin,
      and differences in translational control were more prominent than alterations in
      transcriptional regulation. Strikingly, genes that were translationally activated
      by IPF-derived ECM were enriched for those encoding ECM proteins detected in IPF
      tissue. We determined that genes encoding IPF-associated ECM proteins are targets
      for miR-29, which was downregulated in fibroblasts grown on IPF-derived ECM, and
      baseline expression of ECM targets could be restored by overexpression of miR-29.
      Our data support a model in which fibroblasts are activated to pathologically
      remodel the ECM in IPF via a positive feedback loop between fibroblasts and
      aberrant ECM. Interrupting this loop may be a strategy for IPF treatment. 

PMID- 24590290
TI  - SOX2 and p63 colocalize at genetic loci in squamous cell carcinomas.
AB  - The transcription factor SOX2 is an essential regulator of pluripotent stem cells
      and promotes development and maintenance of squamous epithelia. We previously
      reported that SOX2 is an oncogene and subject to highly recurrent genomic
      amplification in squamous cell carcinomas (SCCs). Here, we have further
      characterized the function of SOX2 in SCC. Using ChIP-seq analysis, we compared
      SOX2-regulated gene profiles in multiple SCC cell lines to ES cell profiles and
      determined that SOX2 binds to distinct genomic loci in SCCs. In SCCs, SOX2
      preferentially interacts with the transcription factor p63, as opposed to the
      transcription factor OCT4, which is the preferred SOX2 binding partner in ES
      cells. SOX2 and p63 exhibited overlapping genomic occupancy at a large number of
      loci in SCCs; however, coordinate binding of SOX2 and p63 was absent in ES cells.
      We further demonstrated that SOX2 and p63 jointly regulate gene expression,
      including the oncogene ETV4, which was essential for SOX2-amplified SCC cell
      survival. Together, these findings demonstrate that the action of SOX2 in SCC
      differs substantially from its role in pluripotency. The identification of the
      SCC-associated interaction between SOX2 and p63 will enable deeper
      characterization the downstream targets of this interaction in SCC and normal
      squamous epithelial physiology. 

PMID- 24590293
TI  - Neferine prevented hyperglycemia-induced endothelial cell apoptosis through
      suppressing ROS/Akt/NF-kappaB signal.
AB  - Diabetes mellitus has been identified as a major risk factor for cardiovascular
      diseases. High glucose-induced endothelial dysfunction and apoptosis is an
      important pathological feature of diabetic vasculopathy. Neferine, an alkaloid
      ingredient in lotus seed embryo has many biological actions such as anticancer
      and antioxidant. But little is known about whether Neferine protects endothelial
      cells against high glucose-induced oxidative stress and apoptosis. The present
      study was conducted to investigate the preventive effects of Neferine on
      hyperglycemia-induced injury of human umbilical vein endothelial cells (HUVECs).
      Our study showed that Neferine pretreatment effectively suppressed high glucose
      induced HUVECs apoptosis. Also, Neferine pretreatment inhibited the augment of
      reactive oxygen species (ROS) in high glucose-treated HUVECs. The changes of SOD
      and MDA level in high glucose-treated HUVECs were also prevented by Neferine.
      Further study showed that Neferine did not affect the phosphorylation of JNK and
      p38 in high glucose-treated HUVECs. Interestingly, Neferine markedly inhibited
      high glucose-induced activation of PI3K/Akt pathway in HUVECs. High glucose
      induced activation of NF-kappaB signal was also obviously suppressed by Neferine
      pretreatment. Collectively, we found that Neferine inhibited high glucose-induced
      endothelial apoptosis via blocking ROS/Akt/NF-kappaB pathway, which provides the
      evidence for using Neferine to treat diabetic vasculopathy.

PMID- 24590291
TI  - DLC1-dependent parathyroid hormone-like hormone inhibition suppresses breast
      cancer bone metastasis.
AB  - Bone metastasis is a frequent complication of breast cancer that is often
      accelerated by TGF-beta signaling; however, little is known about how the TGF
      beta pathway is regulated during bone metastasis. Here we report that deleted in
      liver cancer 1 (DLC1) is an important regulator of TGF-beta responses and
      osteolytic metastasis of breast cancer cells. In murine models, breast cancer
      cells lacking DLC1 expression exhibited enhanced capabilities of bone metastasis.
      Knockdown of DLC1 in cancer cells promoted bone metastasis, leading to manifested
      osteolysis and accelerated death in mice, while DLC1 overexpression suppressed
      bone metastasis. Activation of Rho-ROCK signaling in the absence of DLC1 mediated
      SMAD3 linker region phosphorylation and TGF-beta-induced expression of
      parathyroid hormone-like hormone (PTHLH), leading to osteoclast maturation for
      osteolytic colonization. Furthermore, pharmacological inhibition of Rho-ROCK
      effectively reduced PTHLH production and breast cancer bone metastasis in vitro
      and in vivo. Evaluation of clinical breast tumor samples revealed that reduced
      DLC1 expression was linked to elevated PTHLH expression and organ-specific
      metastasis to bone. Overall, our findings define a stroma-dependent paradigm of
      Rho signaling in cancer and implicate Rho-TGF-beta crosstalk in osteolytic bone
      metastasis. 

PMID- 24590292
TI  - Disrupting hedgehog and WNT signaling interactions promotes cleft lip
      pathogenesis.
AB  - Cleft lip, which results from impaired facial process growth and fusion, is one
      of the most common craniofacial birth defects. Many genes are known to be
      involved in the etiology of this disorder; however, our understanding of cleft
      lip pathogenesis remains incomplete. In the present study, we uncovered a role
      for sonic hedgehog (SHH) signaling during lip fusion. Mice carrying compound
      mutations in hedgehog acyltransferase (Hhat) and patched1 (Ptch1) exhibited
      perturbations in the SHH gradient during frontonasal development, which led to
      hypoplastic nasal process outgrowth, epithelial seam persistence, and cleft lip.
      Further investigation revealed that enhanced SHH signaling restricts canonical
      WNT signaling in the lambdoidal region by promoting expression of genes encoding
      WNT inhibitors. Moreover, reduction of canonical WNT signaling perturbed
      p63/interferon regulatory factor 6 (p63/IRF6) signaling, resulting in increased
      proliferation and decreased cell death, which was followed by persistence of the
      epithelial seam and cleft lip. Consistent with our results, mutations in genes
      that disrupt SHH and WNT signaling have been identified in both mice and humans
      with cleft lip. Collectively, our data illustrate that altered SHH signaling
      contributes to the etiology and pathogenesis of cleft lip through antagonistic
      interactions with other gene regulatory networks, including the canonical WNT and
      p63/IRF6 signaling pathways. 

PMID- 24590294
TI  - Effect and mechanisms of human Wharton's jelly-derived mesenchymal stem cells on
      type 1 diabetes in NOD model.
AB  - Type 1 diabetes is an autoimmune disease that results from an inflammatory
      destruction of beta-cells in islets. Mesenchymal stem cells derived from
      Wharton's jelly (WJ-MSCs) own a peculiar immunomodulatory feature and might
      reverse the inflammatory destruction and repair the function of beta-cells. Sixty
      NOD mice were divided into four groups, including normal control group, WJ-MSCs
      prevention group (before onset), WJ-MSCs treatment group (after onset), and
      diabetic control group. After homologous therapy, onset time of diabetes, levels
      of fasting plasma glucose (FPG), fed blood glucose and C-peptide, regulation of
      cytokines, and islet cells were examined and evaluated. After WJ-MSCs infusion,
      FPG and fed blood glucose in WJ-MSCs treatment group decreased to normal level in
      6-8 days and maintained for 6 weeks. Level of fasting C-peptide of these mice was
      higher compared to diabetic control mice (P=0.027). In WJ-MSCs prevention group,
      WJ-MSCs played a protective role for 8-week delayed onset of diabetes, and
      fasting C-peptide in this group was higher compared to the other two diabetic
      groups (P=0.013, 0.035). Compared with diabetic control group, frequencies of
      CD4+CD25+Foxp3+ Tregs in WJ-MSCs prevention group and treatment group were
      higher, while levels of IL-2, IFN-gamma, and TNF-alpha were lower (P<0.001); the
      degree of insulitis was also depressed, especially for WJ-MSCs prevention group
      (P<0.05). Infusion of WJ-MSCs could aid in T1DM through regulation of the
      autoimmunity and recovery of islet beta-cells no matter before or after onset of
      T1DM. WJ-MSCs might be an effective method for T1DM.

PMID- 24590295
TI  - Thyroid fine-needle aspiration: the relevance of BRAF mutation testing.

PMID- 24590296
TI  - Redesigning hospital alarms for patient safety: alarmed and potentially
      dangerous.

PMID- 24590297
TI  - Fabrication and magnetic properties of nickel dodecahedra.
AB  - Here we report a one-pot route for the synthesis of nickel dodecahedra with 52.3
      +/- 0.1 emu g(-1) of saturation magnetization. The procedure is very simple, and
      only three chemicals (NiCl2.6H2O, isopropanol and polyvinylpyrrolidone) are used
      throughout the entire synthetic process. During the reaction, it is believed that
      the application of isopropanol and the amount of polyvinylpyrrolidone play an
      essential role in forming the dodecahedral morphology of the final product.
      Furthermore, a formation process of twinning and the influence of reaction
      kinetic factors were proposed to explain the formation of nickel dodecahedra. 

PMID- 24590299
TI  - Re: a systematic review to assess comparative effectiveness studies in epidural
      steroid injections for lumbar spinal stenosis and to estimate reimbursement
      amounts.

PMID- 24590300
TI  - Reply: To PMID 23953016.

PMID- 24590301
TI  - Lessons learned through leadership: how to avoid looking like an onion with your
      head stuck in the ground and your feet above.

PMID- 24590302
TI  - A subtraction pipeline for automatic detection of new appearing multiple
      sclerosis lesions in longitudinal studies.
AB  - INTRODUCTION: Time-series analysis of magnetic resonance images (MRI) is of great
      value for multiple sclerosis (MS) diagnosis and follow-up. In this paper, we
      present an unsupervised subtraction approach which incorporates multisequence
      information to deal with the detection of new MS lesions in longitudinal studies.
      METHODS: The proposed pipeline for detecting new lesions consists of the
      following steps: skull stripping, bias field correction, histogram matching,
      registration, white matter masking, image subtraction, automated thresholding,
      and postprocessing. We also combine the results of PD-w and T2-w images to reduce
      false positive detections. RESULTS: Experimental tests are performed in 20 MS
      patients with two temporal studies separated 12 (12M) or 48 (48M) months in time.
      The pipeline achieves very good performance obtaining an overall sensitivity of
      0.83 and 0.77 with a false discovery rate (FDR) of 0.14 and 0.18 for the 12M and
      48M datasets, respectively. The most difficult situation for the pipeline is the
      detection of very small lesions where the obtained sensitivity is lower and the
      FDR higher. CONCLUSION: Our fully automated approach is robust and accurate,
      allowing detection of new appearing MS lesions. We believe that the pipeline can
      be applied to large collections of images and also be easily adapted to monitor
      other brain pathologies.

PMID- 24590303
TI  - Model identification of a template-directed peptide network for optimization in a
      continuous reactor.
AB  - The production rate and selectivity of a cross-catalytic peptide network are
      optimized in a simulated continuous reaction process, under a peptide solubility
      constraint. The steady state of this open process is not the equilibrium state,
      and the optimal solution employs diverse cooperative components. 

PMID- 24590304
TI  - Associations of arterial stiffness and cognitive function with physical fitness
      in patients with chronic stroke.
AB  - OBJECTIVE: To determine whether arterial stiffness is associated with cognitive
      function after adjustment for physical fitness in patients with chronic stroke.
      METHODS: Cross-sectional analyses were conducted in 102 patients with chronic
      stroke who participated in an exercise rehabilitation programme. Carotid femoral
      pulse wave velocity and augmentation index were measured as indices of arterial
      stiffness and central systolic loading. Cognitive function was assessed with the
      Mini Mental State Examination. Parameters of physical fitness included the 6-min
      walk test, flexibility, balance, and muscle strength tests. RESULTS: Carotid
      femoral pulse wave velocity was significantly associated with Mini Mental State
      Examination (r = -0.45, p < 0.01) and parameters of physical fitness (r = -0.45~ 
      0.55, p  < 0.01, all). Mini Mental State Examination was significantly associated
      with parameters of physical fitness (r = 0.32~0.46, p < 0.01, all). In
      multivariable linear regression models, carotid femoral pulse wave velocity was
      inversely associated with Mini Mental State Examination after adjustment for
      multiple risk factors (beta = -0.33, p = 0.01). However, the association was
      attenuated and became non-significant after additional adjustment for physical
      fitness (beta = -0.11, p = 0.39). CONCLUSION: Arterial stiffness measured by
      carotid femoral pulse wave velocity is associated with cognitive function in
      patients with chronic stroke, but not after adjustment for physical fitness.
      Maintaining appropriate levels of physical fitness may have a favourable effect
      on both vascular and cognitive function in patients with stroke.

PMID- 24590305
TI  - Systemic plumbism following remote ballistic injury.
AB  - We report an unusual case of systemic lead poisoning, i.e., plumbism, following a
      remote gunshot injury to the right femur. Plumbism is a rare side-effect of
      penetrating projectiles and has been shown to be directly related to the degree
      of ballistic fragmentation, as well as to the impact location, with intra
      synovial, intra-osseous, head, spine and maxillofacial injuries having the
      highest correlation. Our patient, a 44-year-old male, presented to the ER with a
      3-week history of mid epigastric cramping abdominal pain and intermittent
      vomiting as well as mild mental status changes. Abdominal radiographs and
      ultrasound were noncontributory. Laboratory findings were notable for underlying
      microcytic anemia with basophilic stippling observed on peripheral blood smear.
      Serum iron studies were normal. Lead levels were found to be elevated at 306
      MUg/dl. Prior EGD had demonstrated mild erosive gastritis with subsequent
      multiple negative gastric lavages. The patient's past medical history was notable
      for a previous gunshot injury to the right femur with open fracture 2 years
      previously. Radiographs of the proximal right lower extremity, subsequent
      ultrasound and CT demonstrated an uncomplicated healed fracture of the mid right
      femoral diaphysis with an adjacent partially cystic lesion, an approximately 7-cm
      collection in the medial soft tissues containing internal ballistic fragments.
      Mottled surrounding capsular density was observed with mural calcific and
      micrometallic fragments. Systemic plumbism was suspected in relation to the
      remote ballistic injury and chelation therapy was initiated. Following surgical
      removal of the encapsulated fluid collection, systemic lead levels were observed
      to decline precipitously. The abdominal and CNS symptoms resolved in due course
      and the patient was discharged on oral chelation therapy.

PMID- 24590306
TI  - Using plasma vitamin D concentration as a surrogate marker to predict drug
      response: a new chapter in the management of inflammatory bowel disease and
      beyond?

PMID- 24590307
TI  - JPEN Journal Club 3. When and why to randomize.

PMID- 24590311
TI  - Synergistic effects of proteasome inhibitor carfilzomib in combination with
      tyrosine kinase inhibitors in imatinib-sensitive and -resistant chronic myeloid
      leukemia models.
AB  - The tyrosine kinase inhibitor (TKI) imatinib has transformed the treatment and
      outlook of chronic myeloid leukemia (CML); however, the development of drug
      resistance and the persistence of TKI-resistant stem cells remain obstacles to
      eradicating the disease. Inhibition of proteasome activity with bortezomib has
      been shown to effectively induce apoptosis in TKI-resistant cells. In this study,
      we show that exposure to the next generation proteasome inhibitor carfilzomib is
      associated with a decrease in ERK signaling and increased expression of Abelson
      interactor proteins 1 and 2 (ABI-1/2). We also investigate the effect of
      carfilzomib in models of imatinib-sensitive and -resistant CML and demonstrate a
      potent reduction in proliferation and induction of apoptosis in a variety of
      models of imatinib-resistant CML, including primitive CML stem cells. Carfilzomib
      acts synergistically with the TKIs imatinib and nilotinib, even in imatinib
      resistant cell lines. In addition, we found that the presence of immunoproteasome
      subunits is associated with an increased sensitivity to carfilzomib. The present
      findings provide a rational basis to examine the potential of carfilzomib in
      combination with TKIs as a potential therapy for CML, particularly in imatinib
      resistant disease. 

PMID- 24590312
TI  - Mass balance and metabolism of the antimalarial pyronaridine in healthy
      volunteers.
AB  - This was a single dose mass balance and metabolite characterization study of the
      antimalarial agent pyronaridine. Six healthy male adults were administered a
      single oral dose of 720 mg pyronaridine tetraphosphate with 800 nCi of
      radiolabeled (14)C-pyronaridine. Urine and feces were continuously collected
      through 168 h post-dose, with intermittent 48 h collection periods thereafter
      through 2064 h post-dose. Drug recovery was computed for analyzed samples and
      interpolated for intervening time periods in which collection did not occur.
      Blood samples were obtained to evaluate the pharmacokinetics of total
      radioactivity and of the parent compound. Total radioactivity in urine, feces,
      and blood samples was determined by accelerator mass spectrometry (AMS); parent
      concentrations in blood were determined with LC/MS. Metabolite identification
      based on blood, urine, and feces samples was conducted using a combination of LC
      + AMS for identifying radiopeaks, followed by LC/MS/MS for identity
      confirmation/elucidation. The mean cumulative drug recovery in the urine and
      feces was 23.7 and 47.8 %, respectively, with an average total recovery of 71.5
      %. Total radioactivity was slowly eliminated from blood, with a mean half-life of
      33.5 days, substantially longer than the mean parent compound half-life of 5.03
      days. Total radioactivity remained detectable in urine and feces collected in the
      final sampling period, suggesting ongoing elimination. Nine primary and four
      secondary metabolites of pyronaridine were identified. This study revealed that
      pyronaridine and its metabolites are eliminated by both the urinary and fecal
      routes over an extended period of time, and that multiple, varied pathways
      characterize pyronaridine metabolism.

PMID- 24590313
TI  - Elucidation of in vitro phase I metabolites of droperidol using UPLC-QTOF MS.
AB  - Droperidol, an antidopaminergic drug clinically used as an antiemetic and
      antipsychotic, has been reported to induce cardiac toxicity in patients. Due to
      the close relationship between drug metabolism and efficiency and toxicity, the
      present study aims to investigate the phase I metabolites using ultra-performance
      liquid chromatography-quadrupole time-of-flight mass spectrometry. The NADPH
      supplemented phase I incubation system was used to elucidate the in vitro phase I
      metabolites. Five metabolites were detected after droperidol was incubated with
      phase I incubation mixture, including one hydrogenated droperidol, three
      oxidative metabolites, and one N-dealkylated droperidol, elucidated by individual
      retention time and MS/MS fragmentation. Due to the existed phase II metabolic
      reaction, further phase II metabolism should be investigated in the future. In
      conclusion, the phase I metabolism of droperidol was investigated in the present
      study, and five new metabolites were identified. The efficiency and toxicity of
      these phase I metabolites should be investigated in the future. 

PMID- 24590314
TI  - Regulation of CCM genes in Chlamydomonas reinhardtii during conditions of light
      dark cycles in synchronous cultures.
AB  - We have investigated transcript level changes of CO(2)-concentrating mechanism
      (CCM) genes during light-dark (12 h:12 h) cycles in synchronized Chlamydomonas
      reinhardtii at air-level CO(2). CCM gene transcript levels vary at various times
      of light-dark cycles, even at same air-level CO(2). Transcripts of inorganic
      carbon transporter genes (HLA3, LCI1, CCP1, CCP2 and LCIA) and mitochondrial
      carbonic anhydrase genes (CAH4 and CAH5) are up regulated in light, following
      which their levels decline in dark. Contrastingly, transcripts of chloroplast
      carbonic anhydrases namely CAH6, CAH3 and LCIB are up regulated in dark. CAH3 and
      LCIB transcript levels reached maximum by the end of dark, followed by high
      expression into early light period. In contrast, CAH6 transcript level stayed
      high in dark, followed by high level even in light. Moreover, the up regulation
      of transcripts in dark was undone by high CO(2), suggesting that the dark induced
      CCM transcripts were regulated by CO(2) even in dark when CCM is absent. Thus
      while the CAH3 transcript level modulations appear not to positively correlate
      with that of CCM, the protein regulation matched with CCM status: in spite of
      high transcript levels in dark, CAH3 protein reached peak level only in light and
      localized entirely to pyrenoid, a site functionally relevant for CCM. Moreover,
      in dark, CAH3 protein level not only reduced but also the protein localized as a
      diffused pattern in chloroplast. We propose that transcription of most CCM genes,
      followed by protein level changes including their intracellular localization of a
      subset is subject to light-dark cycles.

PMID- 24590315
TI  - Aggressive course in encephalitis with opsoclonus, ataxia, chorea, and seizures:
      the first pediatric case of gamma-aminobutyric acid type B receptor autoimmunity.
AB  - IMPORTANCE: Autoantibodies to the gamma-aminobutyric acid type B (GABAB) receptor
      have recently been identified as a cause of autoimmune encephalitis. Most
      patients with GABAB encephalitis have presented with limbic encephalitis. About
      half of the cases reported have been paraneoplastic in origin, with the majority
      of tumors representing small cell lung cancer. OBSERVATIONS: We describe a 3-year
      old boy who presented with a mixed movement disorder (opsoclonus, ataxia, and
      chorea) as well as seizures refractory to treatment. His seizures required
      continuous pentobarbital sodium infusion to be controlled. Despite treatment with
      intravenous corticosteroids and immunoglobulins, the patient ultimately died of
      overwhelming sepsis. CONCLUSIONS AND RELEVANCE: To our knowledge, this report
      represents the first pediatric case of GABAB-associated encephalitis. Our patient
      presented with encephalopathy, refractory seizures, and a mixed movement disorder
      rather than limbic encephalitis. gamma-Aminobutyric acid type B receptor
      autoimmunity deserves consideration in pediatric patients presenting with
      encephalitis. Immune-mediated encephalitis with autoantibodies directed against
      synaptic proteins has become an important component of the differential diagnosis
      of patients with encephalitis. Current estimates suggest that a substantial
      proportion of patients once suspected to have viral encephalitis in fact have an
      autoimmune etiology for their symptoms.1 Additional autoantigen targets continue
      to be identified, and the phenotypic spectrum associated with autoimmune
      encephalitis continues to expand. We describe a 3-year-old patient who presented
      with acute-onset confusion, opsoclonus, chorea, and intractable seizures.
      Neuroimaging disclosed involvement of the brainstem, basal ganglia, and
      hippocampi. gamma-Aminobutyric acid type B (GABAB) receptor autoantibodies were
      identified in the serum and cerebrospinal fluid (CSF). Despite immunomodulating
      therapy, the patient died of overwhelming sepsis. To our knowledge, this is the
      first description of a pediatric patient with GABAB receptor autoantibodies. The
      presence of opsoclonus, ataxia, and chorea expands the clinical phenotype and
      indicates that GABAB receptor autoimmunity should be considered in cases of
      pediatric encephalitis

PMID- 24590318
TI  - A delicate adjustment: Wallace and Bates on the Amazon and "the problem of the
      origin of species".
AB  - For over a century it has been believed that Alfred Russel Wallace and Henry
      Walter Bates set out for the Amazon in 1848 with the aim of "solving the problem
      of the origin of species". Yet this enticing story is based on only one sentence.
      Bates claimed in the preface to his 1863 book that Wallace stated this was the
      aim of their expedition in an 1847 letter. Bates gave a quotation from the
      letter. But Wallace himself never endorsed or repeated this story. Many writers
      have acknowledged that this letter still survives. Yet the wording is different
      from that quoted by Bates and the letter says nothing of an expedition. It is
      argued that the sentence given by Bates is not a genuine quotation from this or
      any other Wallace letter but was modified by Bates to promote his own reputation.
      More significantly, this leads to the conclusion that there was a very sudden and
      dramatic shift in the way species were thought of and discussed after Darwin's
      Origin of species appeared. Something called "the problem of the origin of
      species" (and similar variants) never occurred before Darwin's book but exploded
      in frequency immediately after it. A profound change in how species origins were
      discussed happened which no one seemed to notice. 

PMID- 24590316
TI  - Mild hyperhomocysteinemia increases brain acetylcholinesterase and
      proinflammatory cytokine levels in different tissues.
AB  - Mild hyperhomocysteinemia is considered to be a risk factor for cerebral and
      cardiovascular disorders and can be modeled in experimental rats. Inflammation
      has been implicated in the toxic effects of homocysteine. Cholinergic signaling
      controls cytokine production and inflammation through the "cholinergic anti
      inflammatory pathway," and brain acetylcholinesterase activity plays a role in
      this regulation. The aim of this present study is to investigate the effect of
      mild chronic hyperhomocysteinemia on proinflammatory cytokine levels in the
      brain, heart, and serum of rats. Activity, immunocontent, and gene expression of
      acetylcholinesterase in the brain and butyrylcholinesterase activity in serum
      were also evaluated. Mild hyperhomocysteinemia was induced in Wistar rats by
      homocysteine administration (0.03 MUmol/g of body weight) twice a day, from the
      30th to the 60th days of life. Controls received saline in the same volumes.
      Results demonstrated an increase in tumor necrosis factor-alpha (TNF-alpha),
      interleukin-1beta (IL-1beta), interleukin-6 (IL-6), and the chemokine monocyte
      chemotactic protein-1 (MCP-1) in the hippocampus, as well as an increase in IL
      1beta and IL-6 levels in cerebral cortex. Acetylcholinesterase activity was
      increased in rats subjected to mild hyperhomocysteinemia in both cerebral
      structures tested; the immunocontent of this enzyme was also increased in the
      cerebral cortex and decreased in the hippocampus. Levels of acetylcholinesterase
      mRNA transcripts were not altered. Peripherally, homocysteine increased TNF
      alpha, IL-6, and MCP-1 levels in the heart and IL-6 levels in serum. Taken
      altogether, these findings suggest that homocysteine promotes an inflammatory
      status that can contribute, at least in part, to neuronal and cardiovascular
      dysfunctions observed in mild hyperhomocysteinemia.

PMID- 24590319
TI  - Synthesis and characterisation of a new anion exchangeable layered hydroxyiodide.
AB  - Lu4O(OH)9I.3H2O is a new member of the anion exchangeable lanthanide hydroxyanion
      family of materials which has been synthesised hydrothermally. Its structure
      comprises positively charged [Lu4O(OH)9(H2O)3](+) layers with exchangeable charge
      balancing iodide anions located in the interlayer gallery. It has been found to
      undergo facile anion exchange reactions with dicarboxylate anions such as
      succinate and terephthalate at room temperature but reacts less readily with
      disulfonate anions such as 1,5- and 2,6-naphthalenedisulfonate under the same
      conditions. At reaction temperatures above 200  degrees C the cationic inorganic
      framework Lu3O(OH)6I.2H2O forms instead of the layered phase. 

PMID- 24590317
TI  - Lipid integration in neurodegeneration: an overview of Alzheimer's disease.
AB  - Various types of lipids and their metabolic products associated with the
      biological membrane play a crucial role in signal transduction, modulation, and
      activation of receptors and as precursors of bioactive lipid mediators.
      Dysfunction in the lipid homeostasis in the brain could be a risk factor for the
      many types of neurodegenerative disorders, including Alzheimer's disease,
      Huntington's disease, Parkinson's disease, and amyotrophic lateral sclerosis.
      These neurodegenerative disorders are marked by extensive neuronal apoptosis,
      gliosis, and alteration in the differentiation, proliferation, and development of
      neurons. Sphingomyelin, a constituent of plasma membrane, as well as its primary
      metabolite ceramide acts as a potential lipid second messenger molecule linked
      with the modulation of various cellular signaling pathways. Excessive production
      of reactive oxygen species associated with enhanced oxidative stress has been
      implicated with these molecules and involved in the regulation of a variety of
      different neurodegenerative and neuroinflammatory disorders. Studies have shown
      that alterations in the levels of plasma lipid/cholesterol concentration may
      result to neurodegenerative diseases. Alteration in the levels of inflammatory
      cytokines and mediators in the brain has also been found to be implicated in the
      pathophysiology of neurodegenerative diseases. Although several mechanisms
      involved in neuronal apoptosis have been described, the molecular mechanisms
      underlying the correlation between lipid metabolism and the neurological deficits
      are not clearly understood. In the present review, an attempt has been made to
      provide detailed information about the association of lipids in neurodegeneration
      especially in Alzheimer's disease. 

PMID- 24590320
TI  - Schwannoma of the pudendal nerve at sciatic notch and differential diagnosis of
      "sitting pain".

PMID- 24590321
TI  - Comparing the effects of pedicle torsion on axial or perforator flaps; improving
      the perforator flap resistance to pedicle torsion with delay phenomenon.
AB  - BACKGROUND: The torsion of the flap's pedicle is one of the most common
      conditions causing vascular compromise. We aimed to compare the resistance to
      torsion of axial flap pedicle and perforator pedicle patterns. In the second part
      of the study, we investigated whether the delay phenomenon is an effective method
      for improving perforator flap resistance to pedicle torsion. METHODS: In the
      first phase, 90 male Wistar rats were randomly divided into two groups:
      perforator and axial. Bilateral groin flaps were elevated in the axial group and
      bilateral posterior thigh perforator-based flaps were elevated in the perforator
      group. Viable flap areas were compared at 90, 180, 270, 360, and 720 degrees of
      pedicle rotation. Microangiographic and histopathological studies were performed.
      RESULT: As a result, necrosis was seen following earlier rotation in the
      perforator group and viable flap areas were also lower. In the second phase,
      after delay procedure, the perforator flaps were exposed to 270, 360, and 720
      degrees of pedicle rotation. With the delay procedure, no significant difference
      in viable flap areas was observed. CONCLUSION: In conclusion, the resistance to
      torsion of the axial flap pedicle pattern was greater than that of the perforator
      pedicle pattern, and the delay procedure was not an effective method for
      improving flap resistance to torsion.

PMID- 24590322
TI  - Free flap lower extremity reconstruction in the obese population: does weight
      matter?
AB  - The obesity epidemic continues to grow, and we have observed greater numbers of
      obese individuals among patients seeking lower extremity reconstruction at our
      institution. These patients may present a greater reconstructive challenge, thus
      we sought to identify risk factors and differences in outcomes among patients
      undergoing lower extremity reconstruction.In this study we have performed a
      retrospective cohort analysis of patients undergoing lower extremity
      reconstruction with free tissue transfer at our institution from 2005 to 2012.
      Patients were classified using the World Health Organization criteria for
      obesity. Records were reviewed for patient characteristics, mechanism of injury,
      indications for reconstruction, and surgical technique, with a focus on
      intraoperative and early postoperative complications and outcomes.A total of 43
      out of the 119 patients undergoing lower extremity reconstruction were obese
      (body mass index >= 30). Mechanism of injury, wound location, and the indications
      for reconstruction were similar in both cohorts. No significant differences were
      found in operative characteristics and techniques, including the type of flap
      utilized, operative time, or thrombotic events. No significant differences were
      seen in complication rates overall, however, obese patients more frequently
      needed second flaps (11.6 vs. 0%, p=0.005).This study concludes that successful
      lower extremity reconstruction can be performed in the obese population, with few
      differences in complication rates and outcomes relative to healthy weight
      patients.

PMID- 24590323
TI  - Reconstruction of porcine critical-sized mandibular defects with free fibular
      flaps: the development of a craniomaxillofacial surgery model.
AB  - Vascularized bone flaps are the well-known standards of care for reconstruction
      of segmental mandibular defects >= 6 cm. We developed a large animal critical
      sized mandibular defect model in which osseous free fibula flaps were used for
      reconstruction.In this study a total of eight 3-month-old Yorkshire pigs
      underwent 6 cm full-thickness resection of the left hemimandible. An osseous free
      fibula flap from the left leg was harvested and contoured to the mandibular
      defect. Bone placement and plate position was confirmed with fluoroscopy. Animals
      were followed with serial radiographs and clinical evaluations.Free fibulas were
      transferred successfully in all eight animals. The average operative time was 346
      minutes, and the average flap ischemia time was 86 minutes. The average volume
      ratio of reconstructed hemimandibles to nonoperated control hemimandibles was
      0.72 +/- 0.33. The average maximum fracture load was 689 +/- 262 N, and the
      average ratio of biomechanical fracture load for these samples compared with
      contralateral control hemimandibles was 0.88 +/- 0.25.It is concluded that the
      porcine osseous free fibula flaps can be reliably harvested and viably
      transferred to critical-sized posterior mandibular defects with acceptable long
      term results. The described microsurgical large animal model is acceptable for
      use in craniomaxillofacial experimentation.

PMID- 24590324
TI  - Massive intercalary reconstruction of lower limb after wide excision of malignant
      tumors: an alternative to amputation or rotationplasty.
AB  - In this study, we present the feasibility of intercalary limb resection and
      massive reconstruction for malignant tumors of lower extremity. Ten cases of
      lower extremity malignancies that had undergone concomitant bone (and/or joint)
      and soft-tissue reconstruction after wide excision exceeding two-thirds of the
      cross-sectional area of the affected limb were reviewed. All cases were indicated
      for amputation because of an expansive tumor, hematoma from a pathologic
      fracture, or previous unplanned excision, with or without critical structure
      involvement. Bone was reconstructed with either an allograft or a tumor
      prosthesis. Soft-tissue reconstruction was performed to achieve critical
      structure and coverage, which was required in all cases. The resection margin was
      clear in all cases, and no soft-tissue graft failure was encountered. During a
      mean follow-up of 26 months (range, 9-42 months), no patient developed local
      recurrence in the resection-reconstruction site. Of the 10 patients, 8 patients
      were able to walk independently, and two were ambulatory but needed crutch
      support outdoors. Massive intercalary resection and reconstruction can be an
      effective treatment option for locally progressed or complicated lower extremity
      malignancies. Considering patient preference and the fair functional outcomes
      observed, it may be a useful alternative to amputation or rotationplasty. 

PMID- 24590325
TI  - Distally based perforator-plus sural fasciocutaneous flap for soft-tissue
      reconstruction of the distal lower leg, ankle, and foot: comparison between
      pediatric and adult patients.
AB  - There are no large series comparing the distally based perforator-plus sural
      fasciocutaneous flap used in pediatric and adult populations. The flaps were
      divided into two groups: the children (patient's age<14 years) group (n=53) and
      the adults (patient's age >= 18 years) group (n=148). We compared flap-viability
      related complications and their potential risk factors. In the patients with at
      least 12-month postoperative follow-up, the reconstruction outcomes, donor-site
      morbidities, and transitory and permanent swelling of the affected lower limb
      were compared. Partial necrosis, marginal necrosis, and overall complication
      rates were 13.2, 3.8, and 17.0% in the pediatric group, and 12.2, 1.4, and 13.6%
      in the adult group, respectively; the differences were not statistically
      significant (p>0.05). Incidences of hypertrophic scar and pruritus at the donor
      site were significantly higher, while incidence of transitory swelling of the
      affected lower limb was significantly lower in the pediatric group. This flap in
      children is similar to that in adults in the reliability.

PMID- 24590326
TI  - A radiographic study of pediatric ulnar anatomy.
AB  - BACKGROUND: The adult ulna has a unique bony architecture that has been described
      in the literature, but, to the best of our knowledge, the ulnar anatomy in
      children has not been described. METHODS: We examined 75 anteroposterior (AP) and
      64 lateral radiographs (29 were bilateral) of 50, 0.5- to 11-year-old, healthy
      children's forearms. On AP radiographs, the total ulnar length, the ulnar
      proximal angle, the ulnar distal angle, and the distance between each angle from
      the tip of the triceps insertion; and, on lateral radiographs, the ulnar length
      and bow deviation were measured. The correlation between age and radiographic
      measurements, differences based on sex, differences compared with adults'
      measurements, and interobserver/intraobserver reliability were assessed. RESULTS:
      Age had a very strong/strong positive correlation with length/distance
      measurements on both AP and lateral radiographs. Only AP ulnar distal angle was
      significantly different between sexes (females > males). Compared with the adult
      ulnar studies, the AP proximal angle in children is significantly smaller and the
      location of this angle is significantly more distal. Interobserver and
      intraobserver reliability were very good for length/distance measurements on AP
      and lateral radiographs. CONCLUSIONS: The knowledge of pediatric ulnar anatomy
      could be helpful in the treatment of forearm deformities due to multiple
      hereditary exostosis and osteogenesis imperfecta, and in the treatment of ulnar
      fractures, particularly in Monteggia variants, where restoration of the correct
      forearm anatomy is essential to obtain good clinical and functional results.
      LEVEL OF EVIDENCE: Study of diagnostic test, Level II.

PMID- 24590327
TI  - Osteogenesis imperfecta and rib fractures in infancy.

PMID- 24590329
TI  - Publication rate of abstracts presented at European Paediatric Orthopaedic
      Society Annual Meetings, 2006 to 2008.
AB  - BACKGROUND: The quality of the abstracts presented at a conference reflects the
      scientific work and level of activity of the scientific association concerned.
      The aim of the present study was to determine the rate of publications of podium
      presentations and posters at the conferences of the European Paediatric
      Orthopaedic Society (EPOS) from 2006 to 2008 and to identify factors that favor
      publication in peer-reviewed journals. The results are compared with those of
      other international societies. METHODS: All 646 abstracts (including podiums,
      posters, and e-posters) presented at the EPOS conferences were investigated using
      the PubMed database to identify any corresponding published articles in the
      journals listed in the database. A period of 5 years before and after the
      relevant conference was used for the PubMed search. Factors influencing
      publication and the quality of the study, such as the type of presentation and
      the level of evidence, were also investigated. RESULTS: A publication rate of
      36.7% was observed, corresponding to 237 publications of 646 abstracts. The
      period to publication showed a mean of 13.88 +/- 1.34 months. It was found that
      abstracts of podium presentations were published significantly more often than
      poster abstracts (P<0.001). Experimental studies, with a publication rate of
      50.9%, showed better results than clinical studies (36.0%). Overall, the articles
      were published in 61 different journals, with the largest number (n=50) appearing
      in the Journal of Pediatric Orthopaedics. In addition, the present study shows
      that abstracts with a higher level of evidence were associated with a higher
      publication rate. CONCLUSIONS: At 36.7%, the rate of publication of EPOS
      abstracts is within the range reached by other specialist orthopaedics societies,
      such as the German Society of Orthopaedics and Trauma Surgery (36%) and the
      British Orthopaedic Association (36%). However, it is lower than the publication
      rate of the Pediatric Orthopaedic Society of North America (POSNA), at 50%. The
      high percentage of unpublished conference abstracts (63%), which did not go
      through a peer-reviewed process, casts doubts upon the practice of utilizing the
      citation of abstracts based purely on conference abstracts. LEVEL OF EVIDENCE:
      Statistical study.

PMID- 24590328
TI  - Socioeconomic factors are associated with frequency of repeat emergency
      department visits for pediatric closed fractures.
AB  - BACKGROUND: Previous research has demonstrated both greater difficulty in
      obtaining follow-up appointments and increased likelihood of return visits to the
      emergency department (ED) for patients with government-funded insurance plans.
      The purpose of the current study is to determine whether socioeconomic factors,
      such as race and insurance type, are associated with the frequency of repeat ED
      visits in pediatric patients with closed fractures. METHODS: A review of ED visit
      data over a 2-year period from a statewide hospital discharge database in New
      York was conducted. Discharges for patients with a unique person identifier in
      the database age 17 years and younger were examined for an ICD-9 diagnosis of
      closed upper or lower extremity fracture. Age, sex, race, and insurance type for
      patients with a return ED visit within 8 weeks for the same fracture diagnosis
      were compared with those without a return visit using standard univariate
      statistical tests and logistic regression analyses. RESULTS: Of the 68,236 visits
      reviewed, the revisit rate was 0.85%. Patients of nonwhite or unidentified race
      were significantly more likely to have a revisit than white patients (OR, 1.27;
      P=0.006). Patients with government-funded insurance were significantly more
      likely to have a revisit than those without government-funded insurance (OR,
      1.55; P<0.001). Patients with private insurance were significantly less likely to
      have a revisit than those without private insurance (OR, 0.72; P=0.001).
      CONCLUSIONS: Our analysis revealed that nonwhite patients are more likely to
      return to the ED within 8 weeks for the same fracture diagnosis. Patients with
      government insurance are 55% more likely to have a revisit, whereas patients with
      private insurance are 28% less likely to have a revisit. Our results suggest that
      socioeconomic disparities exist in access to orthopaedic care for closed
      fractures in a pediatric population. Physicians and policy makers should be
      mindful of these health care disparities when striving to improve access to care
      among patients and resource utilization in the ED. LEVEL OF EVIDENCE: Prognostic
      level II.

PMID- 24590330
TI  - Patient outcomes in the operative and nonoperative management of high-grade
      spondylolisthesis in children.
AB  - BACKGROUND: The optimal management of high-grade spondylolisthesis in the growing
      child is controversial. Some authors have advocated for surgery in all cases
      regardless of symptoms. Surgical intervention results in a >10% risk of
      complications with increased risk of neurological injury associated with slip
      reduction maneuvers. There is a paucity of literature regarding nonoperative
      management in this setting. This study sought to obtain outcome measures in
      pediatric patients with high-grade spondylolisthesis managed either operatively
      or nonoperatively. METHODS: Database review was performed to identify patients
      with a high-grade (Meyerding grade III to V) spondylolisthesis managed either
      operatively or nonoperatively. Retrospective radiographic and chart review was
      performed. Patients were then contacted by phone to obtain current quality-of
      life measurements using the Scoliosis Research Society (SRS)-30 questionnaire.
      RESULTS: Fifty-three patients were identified for inclusion in the study and 49
      were contacted for 92% follow-up. Twenty-four patients were treated with
      operative intervention, and 25 patients were initially treated nonoperatively,
      but 10 went on to require surgical intervention. Mean age at presentation was
      12.6 years (range, 8 to 17 y) and mean age at follow-up was 20.1 years (range, 10
      to 29 y). There were no outcome differences between the groups. A more kyphotic
      slip angle was associated with worse SRS-30 outcome scores across all groups. In
      the nonoperative group, the slip angle was significantly larger in patients who
      failed conservative treatment (34 +/- 17 degrees) than in those who remained
      nonsurgical at final follow-up (20 +/- 14 degrees). Slip angle in the operative
      group was 27 +/- 14 degrees. In surgical patients, an older age at surgery was
      associated with better SRS-30 outcome scores. CONCLUSIONS: Nonoperative
      management or "watchful waiting" of the minimally symptomatic or asymptomatic
      child with a high-grade spondylolisthesis is safe and does not lead to
      significant problems. Operative intervention for the symptomatic patient achieves
      similar long-term results compared with patients whose minimal symptoms do not
      warrant surgery. Delayed surgical intervention does not result in worse outcomes.
      Regardless of treatment modality, patients with a more kyphotic slip angle tend
      to have a poorer prognosis. LEVEL OF EVIDENCE: Level III.

PMID- 24590331
TI  - "Fight-bite": not just a hand problem.
AB  - Human bite wounds around the knee are rarely seen, yet may require the same
      urgent attention as a fight bite to the hand. Two cases of polymicrobial septic
      arthritis of the knee secondary to a human bite wound are described. In both the
      cases, the diagnosis of the septic arthritis was delayed because the intra
      articular wound was unrecognized. The injuries were initially deemed superficial
      and managed with local wound care. In each case, the knee was flexed at the time
      of injury and the quadriceps tendon was penetrated by a tooth which inoculated
      the knee joint. Septic arthritis of the knee presented, in both cases, 72 hours
      after the injury. These infections proved challenging to treat and required
      multiple surgeries and prolonged antibiotic therapy. The "fight bite" phenomenon
      of the hand is widely recognized and the same phenomenon can occur at the knee. 

PMID- 24590332
TI  - Potential causes of loss of reduction in supracondylar humerus fractures.
AB  - BACKGROUND: Recent biomechanical studies have evaluated the stability of various
      pin constructs for supracondylar humerus fractures, but limited data exist
      evaluating these constructs with clinical outcomes. The goal of this study was to
      review the surgical management of Gartland type II and III supracondylar
      fractures to see whether certain pin configurations increase the likelihood of
      loss of reduction (LOR). METHODS: A total of 192 patients treated with a
      displaced supracondylar fracture were evaluated. LOR was defined as a change >10
      degrees in either plane from its intraoperative reduction. Fracture
      classification, comminution, and location were documented. Intraoperative films
      were assessed for number of pins, location of pins both medial and lateral,
      bicortical purchase, pin spread at the fracture site, and pin divergence.
      RESULTS: Ninety-four patients had type II fractures, and 98 had type III
      fractures. The average patient age was 5.7+/-2.3 years. Extension-type injuries
      represented 98% of fractures. LOR was noted in 4.2% of patients. Age (P=0.48) and
      sex (P=0.61) were not associated with LOR. Fracture characteristics including
      type (P=0.85), comminution (P=0.99), and location (P=0.88) were not associated
      with LOR. Fractures treated with lateral-entry pins only or with 2 pins were no
      more likely to lose reduction (P=0.88 and 0.91). Pin spread at the fracture site
      was associated with LOR with less spread increasing the likelihood of failure
      (P=0.02). Fractures that lost reduction had an average pin spread of 9.7 mm [95%
      confidence interval (CI), 6.3-13.2) or 28% (95% CI, 26-31) of the humerus width
      compared with 13.7 mm (95% CI, 13-14.4) or 36% (95% CI, 13-60) of the humerus
      width for those that remained aligned. CONCLUSIONS: LOR after percutaneous
      fixation of supracondylar fractures occurs relatively infrequently at a rate of
      4.2%. This study suggests that pin spread is an important factor associated with
      preventing LOR with a goal of pin spacing at least 13 mm or 1/3 the width of the
      humerus at the level of the fracture. LEVEL OF EVIDENCE: Retrospective study;
      level II.

PMID- 24590333
TI  - Approaches to treatment of unifocal langerhans cell histiocytosis: is biopsy
      alone enough?
AB  - BACKGROUND: Langerhans cell histiocytosis (LCH) is a variable disorder involving
      either single bone or multiorgan systems. The most effective treatment of
      unifocal osseous lesions is debated in the literature. This study describes the
      treatment approaches for LCH and demonstrates the effectiveness of biopsy in
      providing symptom resolution. METHODS: Records of 61 patients diagnosed with LCH
      at a single institution over an 11-year period were reviewed. Thirty-nine
      patients with biopsy-confirmed diagnoses of unifocal osseous LCH were included in
      the analysis. At this institution, lesions are surgically treated by incisional
      biopsy, trocar biopsy, or curettage and grafting. Patients receive chemotherapy
      on a case-by-case basis, depending on the lesion location and size. A Kaplan
      Meier analysis was used to compare time with symptom resolution across treatment
      groups. RESULTS: In the 39 patients with unifocal osseous LCH, treatment
      approaches included incisional biopsy (n = 18, 46.15%), trocar biopsy (n = 8,
      20.51%), incisional biopsy and chemotherapy (n = 8, 20.51%), and biopsy with bone
      grafting (n = 5, 12.82%). The median time from biopsy to symptom resolution was
      5.43 weeks, with an average length of follow-up of 1.59 years. The median time to
      symptom resolution was 3.86 weeks with incisional biopsy, 5.43 weeks with biopsy
      and grafting, 5.64 weeks with trocar biopsy, and 16.57 weeks with biopsy and
      chemotherapy. Overall, there was a significant difference (P = 0.0262) in the
      time to symptom resolution across the different treatment approaches. Time to
      symptom resolution was significantly different between incisional biopsy and
      chemotherapy treatment compared with the incisional biopsy treatment (P =
      0.0027), as well as biopsy with grafting treatment (P = 0.0264). CONCLUSIONS:
      Symptom resolution occurred rapidly after biopsy and did not significantly differ
      among patients who received incisional biopsy, trocar biopsy, or biopsy with
      grafting. Unifocal osseous LCH likely does not require aggressive surgical or
      medical management. Biopsy alone both confirms the diagnosis and precedes a
      predictable resolution of symptoms. LEVEL OF EVIDENCE: Level III, retrospective
      comparative therapeutic study.

PMID- 24590334
TI  - Diagnosis and initial management of musculoskeletal coccidioidomycosis in
      children.
AB  - BACKGROUND: Coccidioidomycosis is an invasive fungal infection caused by the
      inhalation of aerosolized spores of Coccidioides spp., which reside in the arid
      soil of the southwestern United States and northern Mexico. Approximately two
      thirds of cases are asymptomatic, and the remainder usually present with mild flu
      like symptoms. Dissemination of coccidioidomycosis is rare, and can lead to
      extrapulmonic diseases including meningitis, osteomyelitis, and skin and soft
      tissue involvement. The purpose of this study is to report our experience with
      musculoskeletal coccidioidomycosis in children. METHODS: This was a retrospective
      chart review of patients with musculoskeletal infection with Coccidioides spp. at
      a tertiary care pediatric hospital from 1997 to 2010, identified by a search of
      ICD-9 codes and hospital diagnoses. Demographic and clinical data were collected
      from medical records, including the age of the patient, sex, white blood cell
      count, immunocompetence, length of stay, location of involvement, and initial
      treatment. In total, 20 children were identified with musculoskeletal
      coccidioidomycosis. The mean age was 12.3 years (range, 2 to 17 y) at time of
      diagnosis. Diagnostic criteria included positive imaging tests (plain film+MRI),
      serologic positive titers, and/or biopsy with positive cultures. RESULTS: The
      most common presenting symptom was bone pain (100%); only 3 (15%) patients had
      accompanying signs/symptoms of pulmonary infection. Only 2 (5%) patients had a
      white blood cell count >15*10/L (5%). Locations of infection included the foot
      (28%), knee (14%), spine (12%), forearm (10%), lower leg (6%), and other sites
      (30%). Fluconazole was the most common antifungal agent used (75%). Surgical
      intervention was required in 10 (50%) patients. CONCLUSIONS: This is the first
      series that has described musculoskeletal coccidioidomycosis exclusively in
      children. This study suggests that the initial presentation of this disease can
      be nonspecific and difficult to recognize in children. Clinicians should consider
      this diagnosis when faced with a musculoskeletal infection in children from the
      southwestern United States and northern Mexico. LEVEL OF EVIDENCE: IV (case
      series).

PMID- 24590335
TI  - Is there a predilection for breech infants to demonstrate spontaneous
      stabilization of DDH instability?
AB  - BACKGROUND: Breech position subjects the fetal hip to abnormal mechanical forces.
      However, unlike genetic or tissue factors linked to developmental dysplasia of
      the hip (DDH), the causative effect of the breech position ends when the infant
      is born. The purpose of this study was to evaluate the rate of spontaneous
      stabilization in mildly unstable hips of breech-presenting infants compared with
      similarly lax hips in infants with a genetic or tissue-related cause of DDH.
      METHODS: We studied a consecutive series of infants presenting to our institution
      at 8 weeks of age or younger with DDH from January 2008 to January 2012. Infants
      with increased hip laxity on dynamic ultrasound examination but without frank
      instability on clinical provocation maneuvers and no history of prior treatment
      were evaluated. The endpoint was spontaneous stabilization of ultrasound-detected
      instability, or intervention due to persistent instability on follow-up dynamic
      ultrasound. A logistic regression model using backward likelihood ratio method
      was used to analyze predictors of spontaneous stabilization. RESULTS: We
      identified 122 hips in 79 infants with instability on dynamic ultrasound
      evaluation but with stable clinical examinations. Spontaneous stabilization of
      sonographic instability occurred in 90 hips (74%) at a mean age of 9 weeks
      (range, 4 to 18 wk). Breech hips more frequently spontaneously stabilized
      compared with nonbreech hips (80% vs. 66%). Regression analysis determined that
      breech presentation was a strong independent predictor for spontaneous hip
      stabilization (odds ratio, 3.72; 95% confidence interval, 1.45-9.60; P=0.006).
      Sex, family history, intrauterine positioning syndromes, side involved,
      bilateralism, and grade of sonographic hip instability were not independently
      predictive of spontaneous hip stabilization. CONCLUSIONS: DDH infants with a
      history of breech presentation are 3.72 times more likely to experience
      spontaneous resolution of mild hip instability compared with nonbreech infants.
      Awareness that breech presentation is a strong independent predictor of
      spontaneous laxity resolution can guide parental counseling and early care of
      DDH. LEVEL OF EVIDENCE: Level II, prognostic retrospective study.

PMID- 24590336
TI  - Chronic posterior sternoclavicular joint fracture dislocations in children and
      young adults: results of surgical management.
AB  - BACKGROUND: Posterior sternoclavicular joint (SCJ) fracture dislocations in
      children and young adults can be missed on initial examination or could fail
      closed treatment. We hypothesize that surgical interventions (open reduction and
      ligamentous reconstruction or medial clavicle resection depending on the clinical
      scenario) are safe treatment options in patients with symptomatic chronic
      posteriorly displaced SCJ injuries. METHODS: A retrospective review was conducted
      of all patients younger than 25 years of age who underwent surgical treatment for
      chronic posteriorly displaced SCJ injuries at our institution from January 1,
      1999 to December 31, 2011. Chronic injuries were defined as those presenting
      and/or treated at a minimum of 6 weeks from the causative injury. Indications for
      surgery included symptomatic posterior SCJ dislocations or posteriorly angulated
      physeal fractures that did not remodel and were refractory to nonoperative
      treatment. Subjective patient outcomes were obtained by mailed survey and
      telephone contact. Outcomes included a Disabilities of the Arm, Shoulder and Hand
      score, patient-rated levels of pain and/or disability, SCJ stability, and symptom
      improvement. RESULTS: Seven patients met the inclusion criteria and all patients
      reported postoperative improvement or complete resolution of pain at last
      clinical follow-up (mean, 13 mo). At average 5.5 years follow-up, all respondents
      (n=4) reported that their injury did not interfere with normal social activities
      or daily activities. No patients reported difficulty with employment; however,
      all patients reported mild difficulty with return to their level of athletic
      activity before SCJ fracture dislocation. Patients rated their level of pain or
      disability as 1.5 on a 10-point scale. CONCLUSIONS: Surgical intervention can
      reliably provide pain relief and facilitate successful return to activities
      including work in patients with symptomatic chronic posterior SCJ fracture
      dislocations. However, patients must be counseled that they may experience
      persistent symptoms with return to their previous level of sport performance.
      LEVEL OF EVIDENCE: Therapeutic Study-Investigating the Results of Treatment:
      Level IV.

PMID- 24590337
TI  - Development of Clostridium septicum gas gangrene as an adverse effect of
      clindamycin-induced Clostridium difficile infection in a pediatric patient.
AB  - Clostridium myonecrosis or gas gangrene is a life-threatening infection
      characterized by either traumatic or atraumatic etiology. It has been widely
      described in patients with traumatic open wounds and in immunocompromised
      patients, including malignancy. A third source can result from natural flora in
      the gastrointestinal tract after bowel ischemia. This is a rare occurrence and is
      even less commonly described in the pediatric population. We present a pediatric
      patient who developed Clostridium septicum myonecrosis as an iatrogenic
      complication from clindamycin-induced Clostridium difficile ischemic colitis. 

PMID- 24590338
TI  - A critical appraisal of the first-year experience of 5 pediatric orthopaedic
      surgeons.
AB  - BACKGROUND: The transition into practice following a fellowship in pediatric
      orthopaedics is challenging. This study seeks to describe the first-year
      experiences of 5 pediatric orthopaedists. METHODS: An Institutional Review Board
      approved retrospective review was conducted of 5 pediatric orthopaedic surgeons'
      first year in practice. All were fellowship trained and practiced at private or
      academic subspecialty groups. Clinical volume, payor mix, surgical cases, as well
      as complications were evaluated. RESULTS: A total of 1172 surgical procedures
      were available for review. Surgeons performed an average of 234 cases with a mean
      case load of 19.5 procedures per month. Fracture care and surgical management of
      infection represented the largest number of procedures. 42.3% of patients were
      covered by government insurance or were uninsured. Surgeons saw an average of
      30.5 new patients per week in clinic. Of these, 10.7% of patients were scheduled
      for an elective surgical case. A sample of clinical practice revealed that 41.3%
      of patients were covered by government or no insurance. 17.8% of surgical
      patients sustained a complication with the majority being minor or expected.
      18.8% of complications were major and required repeat operation. Complications
      peaked in the fourth month of practice. CONCLUSIONS: Although clinical and
      surgical volumes can vary during the first year of practice, fracture care and
      surgical management of infection represent the majority of operative cases. A
      large portion of surgical volume results from emergent care, whereas elective
      cases are more elusive with only 1 in 10 elective patients resulting in surgical
      treatment. Despite a significant number of untoward events related to surgery,
      major surgical complications are uncommon in the first year of practice. CLINICAL
      RELEVANCE: The majority of surgical cases in the first year of practice are due
      to trauma and infection. A high volume of patients must be seen to establish a
      practice, particularly given the high rate of Medicaid patients. These figures
      provide benchmarks to guide training programs and to establish realistic
      expectations for new pediatric orthopaedic surgeons and their partners.

PMID- 24590339
TI  - A new measurement method in Graf technique: prediction of future acetabular
      development is possible in physiologically immature hips.
AB  - BACKGROUND: Universal ultrasound screening has led to overtreatment and higher
      follow-up rates than are found with clinical examination alone because of high
      incidence of physiologically immature hips (type IIa) in the first weeks of life.
      The ability to predict future acetabular development in physiologically immature
      hips (type IIa) would therefore help to reduce overtreatment and unnecessary
      follow-up. METHODS: We described the gamma-angle to assess the femoral head
      coverage by the acetabular roof, which is measured between the baseline defined
      by Graf and the cartilaginous edge line connecting the inferior point of the
      iliac bone (lower limb) to the medial corner of the acetabular labrum. We
      retrospectively analyzed ultrasonographic findings of infants with developmental
      dysplasia of the hip diagnosed in our hospital and infants with normal hips
      screened in our hospital. Group 1 (35 hips) consists of type IIa hips at initial
      examination and went on to develop into dysplastic hips at follow-up. Group 2
      (279 hips) consists of type IIa hips at initial examination and went on to
      develop into normal hips (type I) at follow-up. RESULTS: The gamma-angles of type
      IIa hips that developed into type I hip at follow-up ranged between 77 and 82.
      The gamma-angles of type IIa hips that developed into hip dysplasia ranged
      between 72 and 78. All type IIa hips that had gamma-angles >78 degrees developed
      into normal hips. We also observed that all type IIa hips that had gamma-angles
      <77 degrees developed into dysplasia. CONCLUSIONS: The amount of cartilage mass
      covering the femoral head, which is a part of the acetabular roof, can therefore
      provide information about future acetabular development. This paper describes a
      new method of measurement (the gamma-angle) that assesses the extent of the
      cartilage coverage of the femoral head, which can predict acetabular development.
      Its use would decrease the rates of unnecessary follow-up and treatment. LEVEL OF
      EVIDENCE: Level II (development of diagnostic criteria on the basis of
      consecutive patients).

PMID- 24590342
TI  - 2012 POSNA-SLAOTI traveling fellowship report.

PMID- 24590340
TI  - Pedicle screw "hubbing" in the immature thoracic spine: a biomechanical and micro
      computed tomography evaluation.
AB  - BACKGROUND: A previous biomechanical study using adult thoracic vertebrae (both
      normal and osteoporotic bone density) demonstrated the deleterious effect of the
      pedicle screw hubbing technique. Pedicle screw "hubbing" involves seating and
      engaging the ventral aspect of the screw head onto the dorsal lamina cortex. This
      technique is postulated to provide a load-sharing effect by improving pullout
      resistance, as well as decreasing cephalocaudad toggling and implant loosening.
      We hypothesized the elastic properties of immature bone may mitigate, and perhaps
      enhance the purported benefits of the hubbing technique. We set out to evaluate
      pullout strength of fixed-head pedicle screws after hubbing versus standard
      insertion in the immature thoracic calf spine. METHODS: Twenty-two (n=22) single
      level disarticulated fresh-frozen immature calf thoracic vertebra specimens
      (ranging from T2 to T13) were prepared. Twelve specimens were instrumented with
      pedicle screws in group I (nonhubbed) and group II (hubbed) in the opposite
      pedicle. Cyclic loading in a cephalocaudad direction was applied for 2000 cycles
      at a rate of 1 Hz. Pullout testing was performed in-line with the midline of the
      vertebra and peak pullout strength was measured in Newtons. Ten different
      specimens underwent micro-computed tomography evaluation to assess for trabecular
      architecture and incidence of iatrogenic microfractures. RESULTS: Hubbed screws
      resulted in significantly lower pullout strength (747+/-197 vs. 922+/-112 N,
      P=0.01). With the hubbing technique, the dorsal cortex demonstrated plastic
      deformation and conformed to the screw head in 83% of cases compared with no
      visible plastic deformation in the control group. Micro-computed tomography
      demonstrated microfractures of the dorsal cortex in 10/10 for the hubbed group
      compared with 1/10 for the control group. CONCLUSIONS: This is the largest study
      ever performed on immature thoracic vertebra to evaluate this topic. Hubbed
      pedicle screws have significantly decreased pullout strength and frequently cause
      iatrogenic microfractures of the dorsal cortex. The unique ability of immature
      bone to exhibit plastic deformation did not provide a protective effect on
      immediate fixation strength, and the increased insertional torque during the
      hubbing technique should not give a false sense of added fixation. This study,
      along with our adult study, provides critical information to the surgeon to avoid
      this common misunderstanding with screw insertion technique. CLINICAL RELEVANCE:
      In vitro fresh-frozen immature calf spine study.

PMID- 24590341
TI  - The sphericity deviation score: a quantitative radiologic outcome measure of Legg
      Calve Perthes disease applicable at the stage of healing and at skeletal
      maturity.
AB  - AIM: This study aimed to determine if a new measure of sphericity of the femoral
      head, the Sphericity Deviation Score (SDS), could be estimated reliably at the
      stage of healing of Legg-Calve-Perthes disease (LCPD) and to determine if the SDS
      at the healing stage reflects the outcome at skeletal maturity. METHODS: The SDS
      was measured with image analysis software on radiographs of 120 children with
      unilateral LCPD at healing of the disease and at skeletal maturity. The
      reproducibility of measurement was assessed. SDS values for hips in different
      Stulberg classes were calculated. On the basis of SDS values at healing of 82
      children, a logistic regression model was developed to determine the probability
      of a good outcome at skeletal maturity. The validity of the model was tested on
      another 38 children. RESULTS: The SDS values at the stage of healing and at
      skeletal maturity were comparable. The SDS values were lowest for Stulberg Class
      I hips and highest for Class IV and V hips. The validated regression model showed
      a very high probability of a good outcome (Stulberg Class I or II) at skeletal
      maturity if the SDS at the stage of healing was below 10. CONCLUSIONS: A reliable
      estimate of the outcome of LCPD at skeletal maturity can be made by computing the
      SDS as soon as the disease heals.

PMID- 24590343
TI  - Proximal femoral resection for the painful dislocated hip in cerebral palsy: does
      indomethacin prevent heterotopic ossification?
AB  - BACKGROUND: Painful hip displacement is difficult to treat in severe cerebral
      palsy. Proximal femoral resection (PFR) is an excellent procedure for pain relief
      but has a high rate of heterotopic ossification (HO). Indomethacin is the gold
      standard therapy used for prevention in hip and acetabular surgery. There is no
      evidence of its benefit in this complex patient group. METHODS: Forty-one
      consecutive patients with severe cerebral palsy underwent 52 primary PFRs for
      severe pain in 2 pediatric orthopaedic units in London, UK. Twenty-one patients
      received a prophylactic postoperative dose of indomethacin for the prevention of
      HO. Notes and radiographs were reviewed independently by 2 orthopaedic trainees.
      RESULTS: The mean age of patients was 14.3 and 14.8 years in the group
      administered with and administered without indomethacin, respectively, and mean
      follow-up was 4.5 and 4.3 years. Five patients in each group developed HO. One
      patient in the indomethacin group was offered reexcision for HO but declined. Two
      in the nonindomethacin group were offered reexcision and one accepted and made a
      good recovery. There was no difference in pain relief between the groups and no
      correlation between the degree of HO and level of postoperative pain.
      CONCLUSIONS: This study does not support the use of prophylactic indomethacin in
      severe cerebral palsy patients undergoing PFR. We also question the importance of
      HO in the outcome of this procedure. LEVEL OF EVIDENCE: Level III.

PMID- 24590345
TI  - The relationship between cam lesion and physis in skeletally immature patients.
AB  - BACKGROUND: Although it has been postulated that injury to the proximal femoral
      physis results in the formation of a cam lesion, a clear causal association has
      not been established. PURPOSE: The purpose of this study was to investigate the
      relationship between the physis and the cam lesion. Our hypotheses were that (1)
      the location of the cam lesion would coincide with the growth plate and (2) the
      distance between the cam lesion and the physis would vary as a function of
      skeletal maturity. METHODS: A retrospective review of the charts and magnetic
      resonance images of adolescent patients with femoroacetabular impingement (FAI)
      was performed. Data collected included the alpha angle, the distance between the
      cam lesion and physis, and physeal status. Linear mixed models were used to
      describe the association between the distance to the cam lesion and physeal
      status. RESULTS: Twenty-four hips in 17 patients were included. The average alpha
      angles were 50.7, 63.2, 64.4, and 63.9 degrees for the anterior, anterosuperior,
      superoanterior, and superior radial magnetic resonance imaging sections. The
      average distance from the cam lesion to the physis was 0.07 cm. There was a
      significant association between physeal status and the distance of the cam lesion
      to the physis. CONCLUSIONS: The location of the cam lesion occurs at the level of
      the physis. In skeletally mature adolescents, the cam lesion is located further
      from the physis than it is in patients whose growth plates remain widely open.
      This suggests a possible causal relationship between physeal injury and the
      development of the cam deformity in patients with femoroacetabular impingement.
      LEVEL OF EVIDENCE: Level IV-retrospective case series.

PMID- 24590344
TI  - International utilization of the SRS-22 instrument to assess outcomes in
      adolescent idiopathic scoliosis: what can we learn from a medical outreach group
      in Ghana?
AB  - BACKGROUND: Cross-cultural studies on adolescent idiopathic scoliosis (AIS)
      populations are limited. This study evaluated the discriminate validity of the
      Scoliosis Research Society Questionnaire (SRS-22) in Ghana between adolescents
      with and without AIS. SRS-22 outcomes from AIS and normal adolescents in Ghana
      were also compared with scores from AIS and normal adolescents in America.
      METHODS: A retrospective review of preoperative SRS-22 questionnaires from Ghana
      and New York City was completed. In Ghana, 84 adolescents without scoliosis
      (healthy-G) (32 female adolescents; mean age, 13.3 y) and 61 patients with AIS
      (AIS-G) (76 female adolescents; mean age, 15.4 y) were administered with the SRS
      22 questionnaire. From the New York City, 450 healthy adolescents (healthy-US)
      (279 female adolescents; mean age, 16 y) and 302 patients with AIS (AIS-US) (227
      female adolescents; mean age, 14.9 y) also completed the SRS-22 questionnaire.
      Patients with curve magnitudes <40 (nonoperative) were then excluded. All 4
      groups were matched based on age and sex, resulting in 4 groups of 40 subjects
      (25 female adolescents; mean age, 14.5 y for all groups). Differences in SRS-22
      scores across the groups were analyzed using analysis of variance and analysis of
      covariance, with the Bonferroni post hoc tests, to control for differences in
      curve magnitude. RESULTS: Mean curve magnitude for the matched groups was larger
      for the AIS-G group [67.2 degrees (range, 42 to 130 degrees)] as compared with
      the AIS-US group [52 degrees (range, 40 to 76 degrees)] (P<0.01). When
      controlling for the curve magnitude, a significant difference between all 4 study
      groups was found within all domains and total score (P<0.01). AIS-G displayed
      significantly lower scores in the activity, image, pain, and mental health
      domains (P<0.01); this reached the minimal clinically importance difference for
      these domains. Healthy-US and healthy-G had better overall and domain-specific
      scores than AIS-US and AIS-G, respectively (P<0.05). CONCLUSIONS: These findings
      illustrate the affect of AIS within a culture as well as across cultures. Healthy
      adolescents had significantly better scores than scoliotic adolescents. Ghanaian
      adolescents had significantly worse Health-Related Quality-of-Life scores than
      American adolescents, especially those suffering from AIS. These differences
      should be kept in mind by those treating this already emotionally vulnerable
      adolescent population. LEVEL OF EVIDENCE: Level II Prognostic.

PMID- 24590346
TI  - Feasibility and safety of perfusion MRI for Legg-Calve-Perthes disease.
AB  - BACKGROUND: Recent studies have suggested that perfusion magnetic resonance
      imaging (pMRI) using gadolinium contrast and a subtraction technique can provide
      useful prognostic information in Legg-Calve-Perthes disease (LCPD) and allow
      earlier stratification for outcome. There are, however, sparse data available
      regarding the feasibility and safety of these studies in children. The purpose of
      this study was to collect this information across multiple centers using pMRI for
      LCPD. METHODS: We retrospectively reviewed a consecutive series of patients with
      confirmed or suspected LCPD who had undergone pMRI at 1 of 5 large tertiary-care
      children's hospitals in the United States, UK, and Mexico. Demographic
      information, type of contrast administered, and requirement for sedation or
      anesthesia were noted. Records were scrutinized for adverse events associated
      with the pMRI protocol. RESULTS: Over the study period, 165 patients underwent
      298 pMRI studies. The median age at the time of imaging was 8.6 years (range,
      2.5to 16.9 y). A total of 252 scans (85%) were performed for a known diagnosis of
      LCPD, whereas 46 were performed for a suspected diagnosis. Ninety-two of the 298
      (31%) pMRIs required sedation, 48 (16%) required general anesthesia, and 122
      (41%) were facilitated by video goggles only. The remaining 36 patients (12%) had
      their studies performed without additional measures. The ages of patients
      requiring sedation (mean, 7.2+/-2.4 y) and anesthesia (mean, 7.7+/-2.3 y) were
      significantly younger than those patients requiring neither (mean, 10.2+/-2.3 y,
      P<0.001). Four patients (1.3%) reported nausea or vomiting as a result of
      sedation. Two patients (0.7%) had complications from intravenous cannulation
      (pull out, difficult access). One child (0.3%) had nausea/vomiting as a result of
      contrast administration. There were no serious adverse events as a result of the
      pMRI protocol; specifically none of nephrogenic systemic fibrosis, anaphylaxis,
      or death. CONCLUSIONS: pMRI is a safe and feasible imaging technique for LCPD.
      Almost half of our patients required either sedation or general anesthesia to
      complete the study. LEVEL OF EVIDENCE: IV (case series).

PMID- 24590347
TI  - What is the best material for molding casts in children?
AB  - BACKGROUND: Casts are used to treat clubfeet, developmental dysplasia of the hip
      (DDH), forearm fractures, and femur fractures. The ability of a cast to maintain
      a desired shape is termed moldability. Clinicians use plaster, fiberglass, and
      soft casts. To our knowledge the biomechanical molding characteristics of these 3
      materials have never been reported. We hypothesized that moldability of plaster
      would be better than fiberglass and fiberglass would be better than soft cast.
      METHODS: We compared 12.7 cm wide casts of plaster, fiberglass, and soft cast.
      Casts were 5 layers thick, prepared in 40 degrees C water, and placed over 2
      layers of cotton padding on 5.1 cm and 15.2 cm diameter foam cylinders. A loading
      device simulated loads applied by clinicians when molding casts for 4 conditions:
      clubfoot (thumb-shaped 50 N load on 5.1 cm model), DDH (thumb-shaped 100 N load
      on 15.2 cm model), forearm fracture (palm-shaped 50 N load on 5.1 cm model), and
      femur fracture (palm-shaped 100 N load on 15.2 cm model). The loading device
      applied molding for 7 minutes. Five casts of each material were made for each
      model. Casts were removed, photographed, and the area of maximal deformation was
      compared with an unmolded cast. A large area of maximal deformation meant that
      the deformation was spread out over a large area, less precise molding. RESULTS:
      In the clubfoot model, plaster was more precise than fiberglass (P=0.002) and
      soft cast (P<0.0001). In the DDH model, plaster was more precise than fiberglass
      (P<0.0001) and soft cast (P<0.0001) and fiberglass was more precise than soft
      cast (P<0.0001).In the femur fracture model, plaster was more precise than
      fiberglass (P=0.001) and soft cast (P=0.001). CONCLUSIONS: The moldability of
      plaster is better than fiberglass and soft cast and fiberglass is better than
      soft cast. CLINICAL RELEVANCE: If precise molding is required, plaster has the
      best moldability. In cases not requiring precise molding, fiberglass and soft
      cast are lightweight, waterproof, and available in child-friendly colors.

PMID- 24590351
TI  - [Ge8(Mo(CO)3)2]4-: an unprecedented 20-electron empty ten-vertex Zintl cluster.
AB  - The unprecedented ten-vertex Zintl anion with the two vertices occupied by
      transition metal fragments, [Ge8(Mo(CO)3)2](4-), has been synthesized and
      structurally characterized, representing the first example of 20-electron empty
      ten-vertex Zintl clusters. The two less cluster-bonding electrons result in a
      markedly distorted bicapped square antiprismatic structure featuring the up
      expanded and down-compressed squares. 

PMID- 24590352
TI  - Spontaneous helical folding of bis(Ni-salphen) complexes in solution and in the
      solid state: spectroscopic tracking of the unfolding process induced by Na(+)
      ions.
AB  - Four kinds of bis(Ni-salphen) complexes containing a 2-methylenepropane-1,3-diyl
      linker were synthesised and characterised. Crystal structural analysis revealed
      that one of the complexes folded into a helical structure, in which two Ni atoms
      were at a distance of 3.2 A from each other. NMR measurements suggested that a
      similar folded state was maintained in solution, and the energy barrier for
      refolding through an unfolded state was 47 kJ mol(-1). The folded complex also
      exhibited a significant bathochromic shift in its UV-Vis absorption structure.
      Addition of sodium ions caused unfolding of the complexes, and the corresponding
      spectra were attributed to a virtually isolated state. DFT calculations
      reproduced well the energy barrier and folding-induced bathochromic shift. 

PMID- 24590353
TI  - Nonlinearity analysis and parameters optimization for an inductive angle sensor.
AB  - Using the finite element method (FEM) and particle swarm optimization (PSO), a
      nonlinearity analysis based on parameter optimization is proposed to design an
      inductive angle sensor. Due to the structure complexity of the sensor,
      understanding the influences of structure parameters on the nonlinearity errors
      is a critical step in designing an effective sensor. Key parameters are selected
      for the design based on the parameters' effects on the nonlinearity errors. The
      finite element method and particle swarm optimization are combined for the sensor
      design to get the minimal nonlinearity error. In the simulation, the nonlinearity
      error of the optimized sensor is 0.053% in the angle range from -60 degrees  to
      60 degrees . A prototype sensor is manufactured and measured experimentally, and
      the experimental nonlinearity error is 0.081% in the angle range from -60 degrees
      to 60 degrees . 

PMID- 24590354
TI  - Contour-based corner detection and classification by using mean projection
      transform.
AB  - Image corner detection is a fundamental task in computer vision. Many
      applications require reliable detectors to accurately detect corner points,
      commonly achieved by using image contour information. The curvature definition is
      sensitive to local variation and edge aliasing, and available smoothing methods
      are not sufficient to address these problems properly. Hence, we propose Mean
      Projection Transform (MPT) as a corner classifier and parabolic fit approximation
      to form a robust detector. The first step is to extract corner candidates using
      MPT based on the integral properties of the local contours in both the horizontal
      and vertical directions. Then, an approximation of the parabolic fit is
      calculated to localize the candidate corner points. The proposed method presents
      fewer false-positive (FP) and false-negative (FN) points compared with recent
      standard corner detection techniques, especially in comparison with curvature
      scale space (CSS) methods. Moreover, a new evaluation metric, called accuracy of
      repeatability (AR), is introduced. AR combines repeatability and the localization
      error (Le) for finding the probability of correct detection in the target image.
      The output results exhibit better repeatability, localization, and AR for the
      detected points compared with the criteria in original and transformed images. 

PMID- 24590357
TI  - Predictors of tumor response in carcinoma of uterine cervix: data from tertiary
      cancer centre in India.
AB  - AIM: The current study was a retrospective analysis to identify the predictors of
      tumor response among cervical cancer patients treated with chemoradiation and
      completed the intended treatment. METHODS: Hundred and twenty eight patients who
      completed the intended therapy as per institute protocol evaluated. Patients were
      treated with external beam radiotherapy to a dose of 50 Gy in 27 fractions
      followed by 21 Gy in three sessions by intracavitory radiotherapy to point A.
      Postoperative patients received 16 Gy in two sessions. Predictors of tumor
      response after treatment were assessed using cox regression. RESULTS: Median time
      to complete tumor response was 12.2 months. Clinical stage emerged as the
      independent prognostic factor. Patients who completed chemotherapy treatment in
      fewer than five cycles had a non-significant increased chance of tumor response
      compared to those completing in five or more cycles. CONCLUSION: Poor tumor
      response after treatment is largely explained by advanced disease stage at
      diagnosis. A strategy for early detection and access to screening facilities will
      improve outcome. Fewer chemotherapy cycles may be beneficial in patients with
      locally advanced carcinoma cervix.

PMID- 24590358
TI  - Clinicians' perspectives on decision making in lower limb amputee rehabilitation.
AB  - OBJECTIVE: Decision making within amputee rehabilitation includes the assessment
      of whether a patient is suitable for a prosthesis and if so, what components to
      provide. This study seeks to increase understanding about clinicians'
      perspectives on what factors influence these decisions. METHOD: One-to-one semi
      structured interviews were completed with 23 experienced clinicians at their
      place of work at 4 UK amputee rehabilitation centres. Thematic analysis using a
      theoretical, semantic approach was used to identify key themes from the data.
      RESULTS: Four key themes were identified: estimating outcome; difficulties
      predicting outcome; patient choice and barriers to prescribing. There was
      variation in the importance placed on each theme between individual clinicians
      and services, with factors such as budget and risk aversion acting as barriers to
      prescribing. Only one of the 4 centres used formal prescribing guidelines.
      CONCLUSION: The results highlight the difficulties clinicians experience in
      estimating outcome and suggest inequity of prosthetic provision in the UK, with
      variation in the provision of high cost items. The development of national
      prescription guidelines is suggested to improve equality of prosthetic provision.

PMID- 24590356
TI  - The Tvv1 retrotransposon family is conserved between plant genomes separated by
      over 100 million years.
AB  - KEY MESSAGE: Combining several different approaches, we have examined the
      structure, variability, and distribution of Tvv1 retrotransposons. Tvv1 is an
      unusual example of a low-copy retrotransposon metapopulation dispersed unevenly
      among very distant species and is promising for the development of molecular
      markers. Retrotransposons are ubiquitous throughout the genomes of the vascular
      plants, but individual retrotransposon families tend to be confined to the level
      of plant genus or at most family. This restricts the general applicability of a
      family as molecular markers. Here, we characterize a new plant retrotransposon
      named Tvv1_Sdem, a member of the Copia superfamily of LTR retrotransposons, from
      the genome of the wild potato Solanum demissum. Comparative analyses based on
      structure and sequence showed a high level of similarity of Tvv1_Sdem with Tvv1
      VB, a retrotransposon previously described in the grapevine genome Vitis
      vinifera. Extending the analysis to other species by in silico and in vitro
      approaches revealed the presence of Tvv1 family members in potato, tomato, and
      poplar genomes, and led to the identification of full-length copies of Tvv1 in
      these species. We were also able to identify polymorphism in UTL sequences
      between Tvv1_Sdem copies from wild and cultivated potatoes that are useful as
      molecular markers. Combining different approaches, our results suggest that the
      Tvv1 family of retrotransposons has a monophyletic origin and has been maintained
      in both the rosids and the asterids, the major clades of dicotyledonous plants,
      since their divergence about 100 MYA. To our knowledge, Tvv1 represents an
      unusual plant retrotransposon metapopulation comprising highly similar members
      disjointedly dispersed among very distant species. The twin features of Tvv1
      presence in evolutionarily distant genomes and the diversity of its UTL region in
      each species make it useful as a source of robust molecular markers for diversity
      studies and breeding.

PMID- 24590359
TI  - Approximately one-half of patients with early-stage hepatocellular carcinoma
      meeting Milan criteria did not receive local tumor destructive or curative
      surgery in the post-MELD exception era.
AB  - BACKGROUND: Since 2002, priority Model for End-stage Liver Disease (MELD)
      exception status has been given to patients with hepatocellular carcinoma (HCC)
      who meet the Milan criteria. Since then, the number of liver transplantations
      performed in patients with HCC has increased, but to the authors' knowledge, few
      studies to date have examined the effect of MELD exception recommendations on
      therapy use and survival rates in a nationwide sample. The current study examines
      therapy use and long-term survival rates among patients with HCC tumors meeting
      the Milan criteria in the post-MELD exception era. METHODS: The current study is
      a retrospective cohort study of 2179 patients with localized HCC meeting the
      Milan criteria who were registered between 2004 and 2007 in the Surveillance,
      Epidemiology, and End Results database. RESULTS: A total of 43% of patients did
      not receive any specific therapy. Overall, the 5-year relative survival rate for
      patients receiving only supportive care was dismal at 24% (95% confidence
      interval [95% CI], 21%-27%), whereas that for patients undergoing liver
      transplantation was 77% (95% CI, 71%-82%). Long-term survival was found to be
      dependent on age, race/ethnicity, and type of therapy received. A multivariate
      Cox proportional hazards model adjusted for age, race/ethnicity, and type of
      therapy received demonstrated that, compared with white patients, black patients
      had significantly poorer survival outcomes (hazards ratio, 1.23; 95% CI, 1.03
      1.47 [P = .02]), whereas Asian/Pacific Islander patients had significantly better
      survival rates when compared with white patients (HR, 0.66; 95% CI, 0.57-0.77 [P
      < .001]). CONCLUSIONS: Despite having localized disease that met transplantation
      criteria, nearly 50% of the large nationwide cohort of patients with HCC in the
      current study received only supportive care and had dismal 5-year relative
      survival rates, especially among black patients.

PMID- 24590360
TI  - The role of transperineal template prostate biopsies in prostate cancer diagnosis
      in biopsy naive men with PSA less than 20 ng ml(-1.).
AB  - BACKGROUND: To compare prostate cancer detection rates between transrectal
      ultrasound (TRUS) prostate biopsy and transperineal template prostate biopsy
      (TPTPB) in biopsy naive men. TRUS biopsy is still regarded as gold standard for
      prostate cancer diagnosis. TPTPB has been shown to improve prostate cancer
      detection in men with rising PSA and previous negative TRUS biopsies. We carried
      out a prospective study performing both biopsies in the same group of men with a
      benign feeling digital rectal examination (DRE), PSA <20 ng ml(-1) and no
      previous prostate biopsies. METHODS: A total of 50 patients with mean age of 67
      years (range: 54-84), mean prostate volume 58 cc (range: 19-165) and mean PSA 8
      ng l(-1) (range: 4-18) underwent standard 12-core TRUS biopsy followed
      immediately by 36-core TPTPB under general anaesthetic. We determined the
      prostate cancer detection rate between the two diagnostic modalities. RESULTS: In
      total, 20/50 (40%) had benign pathology. Of 30/50 (60%) diagnosed with prostate
      cancer, 16 (32%) had positive results in both TRUS and TPTPB, whereas 14 (28%)
      had negative TRUS but positive TPTPB. No cancers were detected solely by TRUS
      biopsy. TRUS biopsy detected cancer in 32% versus 60% with TPTPB. In total,
      19/30(63%) cancers detected by TPTPB had Gleason score > or =7.2 (4%) experienced
      urosepsis, 7 (14%) temporary urinary retention, 16 (32%) mild haematuria and 19
      (38%) haematospermia. CONCLUSIONS: TPTPB is associated with significantly higher
      prostate cancer detection rate than TRUS biopsies in biopsy naive men with a
      benign feeling DRE and PSA <20 ng ml(-1). PSA appears to be better biomarker than
      previously thought.

PMID- 24590361
TI  - Hemodiafiltration beneficially affects QT interval duration and dispersion
      compared to hemodialysis.
AB  - BACKGROUND/AIMS: The prolongation of the QT interval and dispersion could predict
      ventricular arrhythmias. It is not yet established whether there is a difference
      between the effects of hemodialysis and hemodiafiltration on QT interval duration
      and dispersion. METHODS: Data of thirty patients was investigated while they were
      receiving hemodiafiltration over a period of 3 months; then the same group of
      patients was evaluated during treatment with conventional hemodialysis for at
      least another 3 months. Ionic parameters and surface electrocardiograms (ECG)
      were analyzed five times during each session, and 2D, M-mode echocardiography and
      Holter ECGs were performed to acquire additional information. RESULTS: QT
      interval duration (QTmax) and dispersion (QTd) showed a significant increase
      during hemodialysis, but not during hemodiafiltration. QTmax was 388.66 +/- 31.81
      ms at the beginning of hemodialysis and increased to 400.66 +/- 39.12 ms even at
      the 30th minute (p < 0.05). QTd was found to be 31.33 +/- 10.08 ms before the
      commencement of hemodialysis with the largest prolongation being seen at the
      240th minute (51.33 +/- 14.56 ms, p < 0.05). The occurrence of ventricular
      premature beats was significantly higher during hemodialysis (p = 0.018). The
      left atrial diameter significantly decreased at the end of hemodiafiltration (at
      the beginning 45.1 +/- 5.25 mm, at the end 40.77 +/- 5.76 mm; p < 0.05).
      CONCLUSION: Our results suggest a beneficial effect of hemodiafiltration on the
      studied electrocardiographic parameters compared to hemodialysis. The larger
      decrease in the left atrial diameter suggests a more efficient intracardiac
      volume-decreasing potential of hemodiafiltration.

PMID- 24590362
TI  - Serum renalase is related to catecholamine levels and renal function.
AB  - BACKGROUND: Renalase is a kidney-origin monoamine oxidase which can degrade
      catecholamines and regulate blood pressure and cardiovascular function. Although
      it has been shown that serum renalase level significantly decreases with impaired
      renal function, it is not clear whether its level is related to different stages
      of chronic kidney disease (CKD) in patients. METHODS: Eighty-seven patients with
      CKD were selected as subjects of this study to investigate the serum renalase and
      catecholamine (CA) levels by ELISA method, and their relationship with other
      renal function indicators. RESULTS: Serum levels of renalase and renalase
      catecholamine (R/C) ratios were significantly higher in CKD stage 3-5 patients
      (217.4 +/- 103.8 ng/L, 1.00 +/- 0.21) than CKD stage 1-2 patients (162.1 +/- 40.1
      ng/L, 0.82 +/- 0.16; P < 0.05), while there was no significant difference between
      CKD stage 1-2 patients and the normal control group (167.8 +/- 69.4 ng/L, 0.88 +/
      0.17; P > 0.05). Renalase levels were linearly correlated with catecholamine
      levels (R (2) = 0.817; P < 0.01). Serum renalase levels were positively
      correlated with systolic blood pressure (SBP), serum CA, BUN, SCr, UA, and CKD
      stage (P < 0.05), while negatively correlated with RBC, Hb and estimated GFR
      (eGFR) (P < 0.05). R/C ratio was positively correlated with SBP, diastolic blood
      pressure, BUN, SCr, UA, cystatin C, beta2 microglobulin, retinol binding protein
      4 and CKD stage (P < 0.05), while negatively correlated with RBC, Hb, eGFR and
      GFR (P < 0.05). CONCLUSIONS: Serum levels of renalase are highly correlated with
      CA and both serum renalase levels and R/C ratios are related to renal function.

PMID- 24590363
TI  - Population screening for variant Creutzfeldt-Jakob disease using a novel blood
      test: diagnostic accuracy and feasibility study.
AB  - IMPORTANCE: Our study indicates a prototype blood-based variant Creutzfeldt-Jakob
      disease (vCJD) assay has sufficient sensitivity and specificity to justify a
      large study comparing vCJD prevalence in the United Kingdom with a bovine
      spongiform encephalopathy-unexposed population. In a clinical diagnostic
      capacity, the assay's likelihood ratios dramatically change an individual's
      pretest disease odds to posttest probabilities and can confirm vCJD infection.
      OBJECTIVES: To determine the diagnostic accuracy of a prototype blood test for
      vCJD and hence its suitability for clinical use and for screening prion-exposed
      populations. DESIGN, SETTING, AND PARTICIPANTS: Retrospective, cross-sectional
      diagnostic study of blood samples from national blood collection and prion
      disease centers in the United States and United Kingdom. Anonymized samples were
      representative of the US blood donor population (n = 5000), healthy UK donors (n
      = 200), patients with nonprion neurodegenerative diseases (n = 352), patients in
      whom a prion disease diagnosis was likely (n = 105), and patients with confirmed
      vCJD (n = 10). MAIN OUTCOME AND MEASURE: Presence of vCJD infection determined by
      a prototype test (now in clinical diagnostic use) that captures, enriches, and
      detects disease-associated prion protein from whole blood using stainless steel
      powder. RESULTS: The assay's specificity among the presumed negative American
      donor samples was 100% (95% CI, 99.93%-100%) and was confirmed in a healthy UK
      cohort (100% specificity; 95% CI, 98.2%-100%). Of potentially cross-reactive
      blood samples from patients with nonprion neurodegenerative diseases, no samples
      tested positive (100% specificity; 95% CI, 98.9%-100%). Among National Prion
      Clinic referrals in whom a prion disease diagnosis was likely, 2 patients with
      sporadic CJD tested positive (98.1% specificity; 95% CI, 93.3%-99.8%). Finally,
      we reconfirmed but could not refine our previous sensitivity estimate in a small
      blind panel of samples from unaffected individuals and patients with vCJD (70%
      sensitivity; 95% CI, 34.8%-93.3%). CONCLUSIONS AND RELEVANCE: In conjunction with
      the assay's established high sensitivity (71.4%; 95% CI, 47.8%-88.7%), the
      extremely high specificity supports using the assay to screen for vCJD infection
      in prion-exposed populations. Additionally, the lack of cross-reactivity and
      false positives in a range of nonprion neurodegenerative diseases supports the
      use of the assay in patient diagnosis.

PMID- 24590364
TI  - Ultrasensitive, rapid, and selective detection of mercury using graphene assisted
      laser desorption/ionization mass spectrometry.
AB  - We report an extremely sensitive and specific detection of mercuric ions (Hg2+)
      based on graphene assisted laser desorption/ionization mass spectrometry (GALDI
      MS). Combining the highly selective coordination interactions between thymine (T)
      and Hg2+, we present a simple, effective, and novel approach, based on pi-pi
      interactions of the T-Hg2+-T complex and G that can serve as a platform and
      matrix for GALDI-MS. The present sensor not only exhibits high selectivity and
      sensitivity (picomolar) to Hg2+ in aqueous solution, but also can elucidate the
      chemical structures of the metal complexes. The significant advantage in the
      current approach is that there is no need for a sophisticated instrument, and no
      sample pretreatment is required to detect the Hg2+ ions.

PMID- 24590365
TI  - Direct analysis of triacylglycerols from crude lipid mixtures by gold
      nanoparticle-assisted laser desorption/ionization mass spectrometry.
AB  - Triacylglycerols (TAGs), essential energy storage lipids, are easily detected by
      conventional MALDI MS when occurring on their own. However, their signals are
      easily overwhelmed by other lipids, mainly phosphatidylcholines (PCs) and,
      therefore, require purification. In order to profile TAGs from crude lipid
      mixtures without prefractionation, we investigated alternative matrixes that can
      suppress phospholipid ion signals and enhance cationization of TAGs. We found
      that an aqueous solution of citrate-capped gold nanoparticles (AuNPs) with a
      diameter of 12 nm is a superior matrix for the laser desorption/ionization mass
      spectrometry (LDI MS) of TAGs in crude lipid mixtures. The AuNP matrix
      effectively suppressed other lipid signals such as phospholipids and also
      provided 100 times lower detection limit for TAGs than 2,5-dihydroxybenzoic acid
      (DHB), the best conventional MALDI matrix for TAGs. The AuNP-assisted LDI MS
      enabled us to obtain detailed TAG profiles including minor species directly from
      crude beef lipid extracts without phospholipid interference. In addition, we
      could detect TAGs at a trace level from a total brain lipid extract. 

PMID- 24590366
TI  - Isobutanol production as an alternative metabolic sink to rescue the growth
      deficiency of the glycogen mutant of Synechococcus elongatus PCC 7942.
AB  - Glycogen synthesis initiated by glucose-1-phosphate adenylyltransferase (glgC)
      represents a major carbon storage route in cyanobacteria which could divert a
      significant portion of assimilated carbon. Significant growth retardation in
      cyanobacteria with glgC knocked out (DeltaglgC) has been reported in high light
      conditions. Here, we knocked out the glgC gene and analyzed its effects on carbon
      distribution in an isobutanol-producing strain of Synechococcus elongatus PCC7942
      and its parental wild-type strain. We showed that isobutanol production was able
      to partially rescue the growth of DeltaglgC mutant where the growth rescue effect
      positively correlated with the rate of isobutanol production. Using NaH(14)CO3
      incorporation analysis, we observed a 28 % loss of total carbon fixation rate in
      the DeltaglgC mutant compared to the wild-type. Upon expression of the isobutanol
      production pathway in DeltaglgC mutant, the total carbon fixation rate was
      restored to the wild-type level. Furthermore, we showed that 52 % of the total
      carbon fixed was redirected into isobutanol biosynthesis in the DeltaglgC mutant
      expressing enzymes for isobutanol production, which is 2.5 times higher than that
      of the wild-type expressing the same enzymes. These results suggest that
      biosynthesis of non-native product such as isobutanol can serve as a metabolic
      sink for replacing glycogen to rescue growth and restore carbon fixation rate.
      The rescue effect may further serve as a platform for cyanobacteria energy and
      carbon metabolism study. 

PMID- 24590371
TI  - An exemplary relationship between the extent of cofacial aggregation and
      fluorescence quantum yield as exhibited by quaternized amphiphilic
      phthalocyanines.
AB  - The aggregation equilibrium of a series of positively-charged water-soluble
      phthalocyanines (Pcs) was studied in aqueous solution by means of absorption and
      fluorescence techniques. The aggregation equilibrium in water depends on the
      bridging atoms between the pyridyl groups and the Pc core, and on the central
      metal of the Pcs, while N-alkyl groups are virtually uninvolved in the
      aggregation properties. Thus, in the water-methanol mixture, the aggregation
      tendency increased in the order of Zn < Cu <= Ni, Pd when the ligand is the same,
      while the bridging element sulfur gives much more propensity for aggregation
      compared to oxygen. The fluorescence quantum yields of the Pcs showed an
      excellent correlation with the extent of aggregation. 

PMID- 24590373
TI  - Th(VO3)2(SeO3) and Ln(VO3)2(IO3) (Ln = Ce, Pr, Nd, Sm, and Eu): unusual cases of
      aliovalent substitution.
AB  - Th(VO3)2(SeO3) and Ln(VO3)2(IO3) (Ln = Ce, Pr, Nd, Sm, and Eu) have been prepared
      and characterized. Surprisingly, these compounds are isotypic and rather extreme
      examples of aliovalent substitution (Th(IV)vs. Ln(III); Se(IV)O3(2-)vs. I(V)O3(
      )) are possible in this structure type. 

PMID- 24590372
TI  - A successful strategy for the recovering of active P21, an insoluble recombinant
      protein of Trypanosoma cruzi.
AB  - Structural studies of proteins normally require large quantities of pure material
      that can only be obtained through heterologous expression systems and recombinant
      technique. In these procedures, large amounts of expressed protein are often
      found in the insoluble fraction, making protein purification from the soluble
      fraction inefficient, laborious, and costly. Usually, protein refolding is
      avoided due to a lack of experimental assays that can validate correct folding
      and that can compare the conformational population to that of the soluble
      fraction. Herein, we propose a validation method using simple and rapid 1D (1)H
      nuclear magnetic resonance (NMR) spectra that can efficiently compare protein
      samples, including individual information of the environment of each proton in
      the structure. 

PMID- 24590374
TI  - Efficacy and safety of palonosetron for the prophylaxis of chemotherapy-induced
      nausea and vomiting (CINV): a systematic review and meta-analysis of randomized
      controlled trials.
AB  - PURPOSE: Palonosetron, a 5-hydroxytryptamine 3 receptor antagonist (5-HT(3)RA)
      with a strong binding affinity and long half-life, has been used in numerous
      trials for the prophylaxis of chemotherapy-induced nausea and vomiting (CINV). We
      systematically reviewed the efficacy and safety of palonosetron compared to other
      5-HT(3)RAs in CINV prophylaxis. METHODS: A literature search of Ovid MEDLINE,
      EMBASE, and CENTRAL was conducted to identify randomized controlled trials (RCTs)
      comparing palonosetron to other 5-HT(3)RAs in CINV prophylaxis. Primary endpoints
      were the percentage of patients achieving a complete response (CR), complete
      control (CC), no emesis, no nausea, or taking no rescue medications. Secondary
      endpoints were the percentage of patients suffering from 5-HT(3)RA-related
      adverse events. RESULTS: Sixteen RCTs were identified with 2,896 patients
      randomized to palonosetron and 3,187 patients randomized to other 5-HT(3)RAs.
      Palonosetron was consistently statistically superior in CR, CC, no emesis, or no
      nausea and was sometimes superior in no rescue medication. Subgroup analyses
      demonstrated similarity in efficacy between highly and moderately emetogenic
      chemotherapy cohorts. In the acute phase, statistical superiority of palonosetron
      was found for trials that did not allow dexamethasone; conversely, RCTs that
      administered dexamethasone to all patients were nonsignificant. Palonosetron was
      statistically significantly safer in dizziness and mean QTc interval change and
      similar in constipation, headache, and diarrhea. Clinical superiority of
      palonosetron was reached in 3 of 19 analyzed efficacy and safety endpoints.
      CONCLUSIONS: Palonosetron is safer and more efficacious than other 5-HT(3)RAs.
      Future antiemetic guidelines should discuss the merits of including palonosetron
      as a first-line treatment.

PMID- 24590375
TI  - Safety and pharmacokinetic evaluation of repeated intravenous administration of
      palonosetron 0.75 mg in patients receiving highly or moderately emetogenic
      chemotherapy.
AB  - PURPOSE: The aims of this study were to evaluate the safety, efficacy, and
      pharmacokinetics of repeated doses of palonosetron 0.75 mg on days 1 and 3 in
      Japanese patients who received highly or moderately emetogenic chemotherapy.
      METHODS: Twenty- six patients received palonosetron 0.75 mg intravenously before
      chemotherapy on days 1 and 3 plus dexamethasone (12-16 mg before chemotherapy on
      day 1 and 4-8 mg on days 2 and 3). The primary endpoints were safety and
      pharmacokinetics. Pharmacokinetics were evaluated in a subset of patients (n=6).
      Complete response and complete protection were evaluated as secondary endpoints.
      RESULTS: The accumulation ratios for C max and AUClast after the second dose on
      day 3 were 1.42 and 1.37, respectively. These values were consistent with the
      theoretical values expected from the half-life of palonosetron on day 1. Almost
      all of the patients had no nausea or vomiting in the acute phase (complete
      response (CR) rate, 96.2% [25/26]; CP rate, 92.3% [24/26]). In the delayed phase
      (24-192 h post-chemotherapy), the complete response and complete protection rates
      were 76.9% (20/26) and 61.5% (16/26), respectively. Treatment was well tolerated.
      CONCLUSIONS: This is the first study to report the pharmacokinetics of multiple
      doses of palonosetron 0.75 mg, given on days 1 and 3, in Japanese patients.
      Repeated treatment with palonosetron was safe and well tolerated by patients who
      received highly or moderately emetogenic anticancer chemotherapy.

PMID- 24590376
TI  - Evaluation of renal protective effects of inhibiting TGF-beta type I receptor in
      a cisplatin-induced nephrotoxicity model.
AB  - PURPOSE: The use of cisplatin, the first of the platinum-containing anti-cancer
      drugs, is limited by the development of a myriad of adverse reactions, including
      nephrotoxicity. We conducted this study therefore to find out whether SB-431542,
      potent and specific inhibitor of type I transforming growth factor-beta receptor
      (TGF-betaR1), could prevent or attenuate kidney damage in rats, and to elucidate
      its possible mechanism of action. METHODS: Fifty rats were treated with cisplatin
      (10 mg/kg) in the presence (1 and 3 mg/kg) or absence of SB-431542. Morphological
      changes were assessed in kidney sections stained with H/E. Oxidative stress was
      evaluated in kidney homogenates by measuring malondialdehyde (MDA) and superoxide
      dismutase (SOD). Kidney samples were used for measurements of TGF-betaR1, TGF
      beta1 and sCD93 by ELISA. Kidney tissue apoptosis was assessed by measuring
      caspase-3 activity. RESULTS: The renal protective effect of SB-431542 was
      confirmed by the normal appearance of renal tissue and the relatively unaffected
      serum creatinine and urea levels. With SB-431542, there was significantly lower
      renal MDA and increased SOD compared with the cisplatin group. Furthermore, in
      the SB-431542 group, renal TGF-betaR1, TGF-beta1, sCD93 and caspase-3 levels were
      significantly lower. CONCLUSIONS: Inhibition of TGF-betaR1 provides protective
      effects against cisplatin-induced nephrotoxicity through several mechanisms,
      including attenuation of oxidative stress, inhibition of pro-inflammatory
      cytokines, blocking of renal fibrosis markers, and anti-apoptotic effects.

PMID- 24590377
TI  - Shock wave induces biological renal damage by activating excessive inflammatory
      responses in rat model.
AB  - The study was aimed to investigate the potential mechanism of inflammatory renal
      damage induced by shock wave. A total of 48 rats, with the right kidney cut, are
      randomly assigned into control group, ESWL group and ESWL + PDTC group. Rats were
      treated with shock wave at the left kidney. At post-shock wave 3 and 105 days,
      all the animals were sacrificed for detecting the expression of tumor necrosis
      factor (TNF)-alpha, intercellular adhesion molecule (ICAM)-1, and monocyte
      chemoattractant protein (MCP)-1. The inflammatory responses were evaluated by
      detecting the level of myeloperoxidase (MPO) and ED-1. The histological renal
      injury was also examined. Before the animals were sacrificed, the urine samples
      were collected for measuring the values of malondialdehyde (MDA), beta2
      microglobulin, interleukin (IL)-6, and IL-18. At post-shock wave 3 days, the
      higher expression of ICAM-1 and TNF-alpha were observed in shock wave-treated
      kidneys. The level of urine TNF-alpha, IL-6, and IL-18 were also increased
      significantly. Using PDTC obviously decreased the expression of ICAM-1 and TNF
      alpha. It also effectively inhibited the degree of oxidative stress and
      neutrophil infiltration. At post-shock wave 105 days, the expression of MCP-1 and
      the level of urine beta2-microglobulin and IL-18 were increased significantly.
      The histological analysis also indicated more ED-1-positive cells and serious
      fibrosis in shock wave-treated kidneys. PDTC significantly suppressed MCP-1 and
      IL-18 expression, decreased monocyte infiltration, and alleviate the degree of
      interstitium fibrosis. Shock wave triggered excessive inflammatory responses and
      aggravated renal biological damage. Several inflammatory factors including ICAM
      1, MCP-1, and TNF-alpha were considered to play important role in this type of
      renal damage. 

PMID- 24590378
TI  - Sodium/proton exchanger 3 (NHE3) and sudden infant death syndrome (SIDS).
AB  - The sodium/proton exchanger protein 3 (NHE3) is located in chemosensitive areas
      of the medulla oblongata and plays an important role in the central control of
      respiration. Overexpression of NHE3 is correlated with lower respiration and
      might therefore contribute to the vulnerability of infants dying suddenly and
      unexpected (sudden infant death syndrome, SIDS). Our aim in this study was to
      verify already reported genetic variations in the NHE3 gene in an independent
      SIDS cohort from Switzerland. Two single nucleotide polymorphisms (SNPs) in the
      promoter region (G1131A and C1197T) and one variation in the coding sequence of
      exon 16 (C2405T) in the NHE3 gene were analyzed in 160 Caucasian SIDS infants and
      192 Swiss adult controls by using a single base extension method (SNaPshot
      multiplex). No significant differences were detected in the allelic frequencies
      of the three NHE3 polymorphisms between SIDS cases and controls. We conclude that
      the three investigated NHE3 SNPs are unlikely to play a major role in the
      pathogenesis of SIDS in Caucasian infants. However, further genetic
      investigations in different ethnicities are required to determine whether
      variations in NHE3 are associated with an increased SIDS risk. 

PMID- 24590380
TI  - Light-responsive three-dimensional microstructures composed of azobenzene-based
      palladium complexes.
AB  - We describe not only fleeting assembly of photoisomerizable azobenzene-based
      palladium complexes into microstructured crystalline architectures but also their
      light-responsive functions. A transformation in the crystalline morphology from
      two-dimensional (2D) parallelogram-like sheets to three-dimensional (3D) cuboid-
      or rhombus-like structures was achieved by changing the solvent from
      tetrahydrofuran (THF) to acetone and N,N-dimethylformamide (DMF). The sizes of
      the structures, ranging from a few hundred nanometers to several hundred
      micrometers, were also modified by varying the complex concentration. In stark
      contrast to the very stable 2D sheets in the THF-H2O suspensions, exposure of 3D
      structures in polar DMF-H2O suspensions to ultraviolet (UV) light led to fast
      disassembly of the structures into isolated metal complexes and further
      dissociation of free azobenzene ligands from the complexes. In acetone-H2O
      suspensions, interestingly, disassembly of 3D cuboid-like structures into
      isolated complex components occurred upon exposure to UV light without further
      dissociation of azobenzene ligands from the palladium complexes. Considering the
      photoisomerization ability of the azobenzene-based palladium complex in common
      organic solvents, the pi-stacking interactions that support 3D structures are
      likely to be sufficiently weak that they might be broken by the UV-induced trans
      to-cis isomerization in more polar solvent mixtures. As a consequence,
      disassembly proceeded under UV light irradiation. Moreover, the effect of solvent
      polarity on the UV-assisted dissociation (in DMF-H2O) may be associated with the
      coordination ability of solvent molecules with the metal center. 

PMID- 24590379
TI  - Magnetic bead-based separation of sperm from buccal epithelial cells using a
      monoclonal antibody against MOSPD3.
AB  - Forensic DNA analysis of sexual assault evidence requires unambiguous
      differentiation of DNA profiles in mixed samples. To investigate the feasibility
      of magnetic bead-based separation of sperm from cell mixtures using a monoclonal
      antibody against MOSPD3 (motile sperm domain-containing protein 3), 30 cell
      samples were prepared by mixing 10(4) female buccal epithelial cells with sperm
      cells of varying densities (10(3), 10(4), or 10(5) cells/mL). Western blot and
      immunofluorescence assays showed that MOSPD3 was detectable on the membrane of
      sperm cells, but not in buccal epithelial cells. After biotinylated MOSPD3
      antibody was incubated successively with the prepared cell mixtures and avidin
      coated magnetic beads, microscopic observation revealed that each sperm cell was
      bound by two or more magnetic beads, in the head, neck, mid-piece, or flagellum.
      A full single-source short tandem repeat profile could be obtained in 80% of
      mixed samples containing 10(3) sperm cells/mL and in all samples containing
      >=10(4) sperm cells/mL. For dried vaginal swab specimens, the rate of successful
      detection was 100% in both flocked and cotton swabs preserved for 1 day, 87.5% in
      flocked swabs and 40% in cotton swabs preserved for 3 days, and 40% in flocked
      swabs and 16.67% in cotton swabs preserved for 10 days. Our findings suggest that
      immunomagnetic bead-based separation is potentially a promising alternative to
      conventional methods for isolating sperm cells from mixed forensic samples.

PMID- 24590381
TI  - Oxidized low-density lipoprotein increases the proliferation and migration of
      human coronary artery smooth muscle cells through the upregulation of
      osteopontin.
AB  - Smooth muscle cell (SMC) proliferation and migration are known to play a critical
      role in the development of atherosclerosis. Oxidized low-density lipoprotein
      (oxLDL) is involved in the generation of atherosclerotic lesions. Recent studies
      have indicated that oxLDL is a well-established risk factor for atherosclerosis
      that induces vascular smooth muscle cell (VSMC) proliferation and migration;
      however, the exact mechanisms involved have not been fully elucidated. In this
      study, the proliferation of human coronary artery smooth muscle cells (HCASMCs)
      was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
      (MTT) assay. Cell migration was determined by Transwell assay. Osteopontin (OPN),
      matrix metaloproteinase-9 (MMP-9) and alphavbeta3 integrin expression were
      measured by mRNA and western blot analysis. OPN and MMP-9 knockdown cells were
      established through transfection with OPN siRNA or MMP-9 siRNA, respectively. Our
      results revealed that oxLDL makredly promoted HCASMC proliferation and migration
      in a dose-dependent manner. Further experiments demonstrated that oxLDL
      upregulated the expression of OPN and oxLDL. Cell proliferation and migration
      were markedly reduced following the knockdown of the OPN gene in the HCASMCs. We
      then found that treatment with oxLDL induced a concentration-dependent increase
      in MMP-9 mRNA and protein levels in the HCASMCs. These effects were partially
      abrogated by silencing OPN expression or blocking the alphavbeta3 integrin
      pathway. Moreover, cells treated with MMP-9 siRNA or alphavbeta3 antibody showed
      lower proliferation and migration rates. This study provides direct in vitro
      evidence that the exposure of HCASMCs to oxLDL induces the activation of OPN,
      leading to higher protein levels of MMP-9, and to an increased proliferation and
      migration of HCASMCs.

PMID- 24590382
TI  - The emergence of "us and them" in 80 lines of code: modeling group genesis in
      homogeneous populations.
AB  - Psychological explanations of group genesis often require population
      heterogeneity in identity or other characteristics, whether deep (e.g., religion)
      or superficial (e.g., eye color). We used agent-based models to explore group
      genesis in homogeneous populations and found robust group formation with just two
      basic principles: reciprocity and transitivity. These emergent groups
      demonstrated in-group cooperation and out-group defection, even though agents
      lacked common identity. Group formation increased individual payoffs, and group
      number and size were robust to varying levels of reciprocity and transitivity.
      Increasing population size increased group size more than group number, and
      manipulating baseline trust in a population had predictable effects on group
      genesis. An interactive demonstration of the parameter space and source code for
      implementing the model are available online. 

PMID- 24590383
TI  - Elapid snake venom analyses show the specificity of the peptide composition at
      the level of genera Naja and Notechis.
AB  - Elapid snake venom is a highly valuable, but till now mainly unexplored, source
      of pharmacologically important peptides. We analyzed the peptide fractions with
      molecular masses up to 10 kDa of two elapid snake venoms-that of the African
      cobra, N. m. mossambica (genus Naja), and the Peninsula tiger snake, N. scutatus,
      from Kangaroo Island (genus Notechis). A combination of chromatographic methods
      was used to isolate the peptides, which were characterized by combining
      complimentary mass spectrometric techniques. Comparative analysis of the peptide
      compositions of two venoms showed specificity at the genus level. Three-finger (3
      F) cytotoxins, bradykinin-potentiating peptides (BPPs) and a bradykinin inhibitor
      were isolated from the Naja venom. 3-F neurotoxins, Kunitz/basic pancreatic
      trypsin inhibitor (BPTI)-type inhibitors and a natriuretic peptide were
      identified in the N. venom. The inhibiting activity of the peptides was confirmed
      in vitro with a selected array of proteases. Cytotoxin 1 (P01467) from the Naja
      venom might be involved in the disturbance of cellular processes by inhibiting
      the cell 20S-proteasome. A high degree of similarity between BPPs from elapid and
      viperid snake venoms was observed, suggesting that these molecules play a key
      role in snake venoms and also indicating that these peptides were recruited into
      the snake venom prior to the evolutionary divergence of the snakes. 

PMID- 24590386
TI  - [Children with specific language impairment: electrophysiological and
      pedaudiological findings].
AB  - BACKGROUND: Auditory deficits may be at the core of the language delay in
      children with Specific Language Impairment (SLI). It was therefore hypothesized
      that children with SLI perform poorly on 4 tests typically used to diagnose
      central auditory processing disorder (CAPD) as well in the processing of phonetic
      and tone stimuli in an electrophysiological experiment. MATERIAL AND METHODS: 14
      children with SLI (mean age 61,7 months) and 16 children without SLI (mean age
      64,9 months) were tested with 4 tasks: non-word repetition, language
      discrimination in noise, directional hearing, and dichotic listening. The
      electrophysiological recording Mismatch Negativity (MMN) employed sine tones (600
      vs. 650 Hz) and phonetic stimuli (/epsilon/ versus /e/). RESULTS: Control
      children and children with SLI differed significantly in the non-word repetition
      as well as in the dichotic listening task but not in the two other tasks. Only
      the control children recognized the frequency difference in the MMN-experiment.
      The phonetic difference was discriminated by both groups, however, effects were
      longer lasting for the control children. Group differences were not significant.
      CONCLUSIONS: Children with SLI show limitations in auditory processing that
      involve either a complex task repeating unfamiliar or difficult material and show
      subtle deficits in auditory processing at the neural level.

PMID- 24590384
TI  - Monoclonal antibody therapy and renal transplantation: focus on adverse effects.
AB  - A series of monoclonal antibodies (mAbs) are commonly utilized in renal
      transplantation as induction therapy (a period of intense immunosuppression
      immediately before and following the implant of the allograft), to treat steroid
      resistant acute rejections, to decrease the incidence and mitigate effects of
      delayed graft function, and to allow immunosuppressive minimization.
      Additionally, in the last few years, their use has been proposed for the
      treatment of chronic antibody-mediated rejection, a major cause of late renal
      allograft loss. Although the exact mechanism of immunosuppression and allograft
      tolerance with any of the currently used induction agents is not completely
      defined, the majority of these medications are targeted against specific CD
      proteins on the T or B cells surface (e.g., CD3, CD25, CD52). Moreover, some of
      them have different mechanisms of action. In particular, eculizumab, interrupting
      the complement pathway, is a new promising treatment tool for acute graft
      complications and for post-transplant hemolytic uremic syndrome. While it is
      clear their utility in renal transplantation, it is also unquestionable that by
      using these highly potent immunosuppressive agents, the body loses much of its
      innate ability to mount an adequate immune response, thereby increasing the risk
      of severe adverse effects (e.g., infections, malignancies, haematological
      complications). Therefore, it is extremely important for clinicians involved in
      renal transplantation to know the potential side effects of monoclonal antibodies
      in order to plan a correct therapeutic strategy minimizing/avoiding the onset and
      development of severe clinical complications. 

PMID- 24590385
TI  - Electrophysiological characterization of Ts6 and Ts7, K+ channel toxins isolated
      through an improved Tityus serrulatus venom purification procedure.
AB  - In Brazil, Tityus serrulatus (Ts) is the species responsible for most of the
      scorpion related accidents. Among the Ts toxins, the neurotoxins with action on
      potassium channels (alpha-KTx) present high interest, due to their effect in the
      envenoming process and the ion channel specificity they display. The alpha-KTx
      toxins family is the most relevant because its toxins can be used as therapeutic
      tools for specific target cells. The improved isolation method provided toxins
      with high resolution, obtaining pure Ts6 and Ts7 in two chromatographic steps.
      The effects of Ts6 and Ts7 toxins were evaluated in 14 different types of
      potassium channels using the voltage-clamp technique with two-microelectrodes.
      Ts6 toxin shows high affinity for Kv1.2, Kv1.3 and Shaker IR, blocking these
      channels in low concentrations. Moreover, Ts6 blocks the Kv1.3 channel in
      picomolar concentrations with an IC50 of 0.55 nM and therefore could be of
      valuable assistance to further designing immunosuppressive therapeutics. Ts7
      toxin blocks multiple subtypes channels, showing low selectivity among the
      channels analyzed. This work also stands out in its attempt to elucidate the
      residues important for interacting with each channel and, in the near future, to
      model a desired drug. 

PMID- 24590388
TI  - Influences of tobacco advertising exposure and conduct problems on smoking
      behaviors among adolescent males and females.
AB  - INTRODUCTION: Adolescents with conduct problems are more likely to smoke, and
      tobacco advertising exposure may exacerbate this risk. Males' excess risk for
      conduct problems and females' susceptibility to advertising suggest gender
      specific pathways to smoking. We investigated the associations between gender,
      conduct problems, and lifetime smoking and adolescents' exposure to tobacco
      advertising, and we examined prospective relationships with smoking behaviors.
      METHODS: Adolescents completed baseline (2001-2004; n = 541) and 5-year follow-up
      (2007-2009; n =320) interviews for a family study of smoking risk. Baseline
      interviews assessed conduct problems and tobacco advertising exposure; smoking
      behavior was assessed at both timepoints. Generalized linear models analyzed
      gender differences in the relationship between conduct problems, advertising
      exposure, and smoking behavior at baseline and longitudinally. RESULTS: At
      baseline, among males, conduct problems were associated with greater advertising
      exposure independent of demographics and lifetime smoking. Among females at
      baseline, conduct problems were associated with greater advertising exposure only
      among never-smokers after adjusting for demographics. In longitudinal analyses,
      baseline advertising exposure predicted subsequent smoking initiation (i.e.,
      smoking their first cigarette between baseline and follow-up) for females but not
      for males. Baseline conduct problems predicted current (i.e., daily or weekly)
      smoking at follow-up for all adolescents in adjusted models. CONCLUSIONS: The
      findings of this study reinforce that conduct problems are a strong predictor of
      subsequent current smoking for all adolescents and reveal important differences
      between adolescent males and females in the relationship between conduct
      problems, tobacco advertising behavior, and smoking behavior. The findings
      suggest gender-specific preventive interventions targeting advertising exposure
      may be warranted.

PMID- 24590389
TI  - Comparison of plasmapheresis and intravenous immunoglobulin as maintenance
      therapies for juvenile myasthenia gravis.
AB  - IMPORTANCE: Juvenile myasthenia gravis (MG) is a relatively rare autoimmune
      disorder. The comparative efficacy of plasmapheresis (PLEX) vs immunoglobulin as
      maintenance therapy is unclear for this childhood disease. OBJECTIVE: To
      determine whether PLEX or intravenous immunoglobulin (IVIG) therapy is more
      effective as maintenance therapy in this disease. DESIGN, SETTING, AND
      PARTICIPANTS: This retrospective analysis over a 33-year period involved 54
      children and adolescents with juvenile MG at a specialized neuromuscular clinic
      and electromyography laboratory at a tertiary care academic pediatric hospital.
      INTERVENTIONS: Plasmapheresis and IVIG. MAIN OUTCOMES AND MEASURES: Response to
      treatment was measured by both improvement in objective physical examination
      findings and the patients' reported improvement in symptoms and functional
      abilities. RESULTS: Subjective and objective outcomes correlated well. Both PLEX
      and IVIG had high response rates. Of the 27 patients with generalized juvenile MG
      receiving PLEX, IVIG, or both treatments, 7 of 7 patients treated with PLEX alone
      responded, 5 of 10 patients treated with IVIG alone responded, and 9 of 10
      patients who received both responded. There was a significant difference in
      response rates between patients who received PLEX vs IVIG (P = .04). The youngest
      age at which PLEX was initiated via peripheral venous access was 9 years, while
      the youngest child who received IVIG was 9 months old. Thymectomy was performed
      in 17 children, of whom 11 experienced significant postoperative improvement.
      CONCLUSIONS AND RELEVANCE: This study provides class III evidence that PLEX and
      IVIG both have high response rates as maintenance therapies and are reasonable
      therapeutic options for juvenile MG. Plasmapheresis may have a more consistent
      response rate than IVIG in this setting. These findings will provide some
      guidance regarding the approach to therapy for juvenile MG, especially as the
      results differ somewhat from those of studies focusing on adult MG.

PMID- 24590387
TI  - Children's exposure to secondhand and thirdhand smoke carcinogens and toxicants
      in homes of hookah smokers.
AB  - INTRODUCTION: We examined homes of hookah-only smokers and nonsmokers for levels
      of indoor air nicotine (a marker of secondhand smoke) and indoor surface nicotine
      (a marker of thirdhand smoke), child uptake of nicotine, the carcinogen 4
      (methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), and the toxicant acrolein by
      analyzing their corresponding metabolites cotinine, 4-(methylnitrosamino)-1-(3
      pyridyl)-1-butanol (NNAL) and NNAL-glucuronides (total NNAL) and 3
      hydroxypropylmercapturic acid. METHODS: Data were collected at 3 home visits
      during a 7-day study period from a convenience sample of 24 households with a
      child 5 years or younger. Three child urine samples and 2 air and surface samples
      from the living room and the child bedroom were taken in homes of nonsmokers (n =
      5) and hookah-only smokers (n = 19) comprised of daily hookah smokers (n = 8) and
      weekly/monthly hookah smokers (n = 11). RESULTS: Nicotine levels in indoor air
      and on surfaces in the child bedrooms in homes of daily hookah smokers were
      significantly higher than in homes of nonsmokers. Uptake of nicotine, NNK, and
      acrolein in children living in daily hookah smoker homes was significantly higher
      than in children living in nonsmoker homes. Uptake of nicotine and NNK in
      children living in weekly/monthly hookah smoker homes was significantly higher
      than in children living in nonsmoker homes. CONCLUSIONS: Our data provide the
      first evidence for uptake of nicotine, the tobacco-specific lung carcinogen NNK,
      and the ciliatoxic and cardiotoxic agent acrolein in children living in homes of
      hookah smokers. Our findings suggest that daily and occasional hookah use in
      homes present a serious, emerging threat to children's long-term health.

PMID- 24590391
TI  - Modeling possible effects of atypical cerebellar processing on eyeblink
      conditioning in autism.
AB  - Autism is unique among other disorders in that acquisition of conditioned
      eyeblink responses is enhanced in children, occurring in a fraction of the trials
      required for control participants. The timing of learned responses is, however,
      atypical. Two animal models of autism display a similar phenotype. Researchers
      have hypothesized that these differences in conditioning reflect cerebellar
      abnormalities. The present study used computer simulations of the cerebellar
      cortex, including inhibition by the molecular layer interneurons, to more closely
      examine whether atypical cerebellar processing can account for faster
      conditioning in individuals with autism. In particular, the effects of inhibitory
      levels on delay eyeblink conditioning were simulated, as were the effects of
      learning-related synaptic changes at either parallel fibers or ascending branch
      synapses from granule cells to Purkinje cells. Results from these simulations
      predict that whether molecular layer inhibition results in an enhancement or an
      impairment of acquisition, or changes in timing, may depend on (1) the sources of
      inhibition, (2) the levels of inhibition, and (3) the locations of learning
      related changes (parallel vs. ascending branch synapses). Overall, the
      simulations predict that a disruption in the balance or an overall increase of
      inhibition within the cerebellar cortex may contribute to atypical eyeblink
      conditioning in children with autism and in animal models of autism. 

PMID- 24590390
TI  - Assessment of nutrient supplement to reduce gentamicin-induced ototoxicity.
AB  - Gentamicin is an aminoglycoside antibiotic used to treat gram-negative bacterial
      infections. Treatment with this antibiotic carries the potential for adverse side
      effects, including ototoxicity and nephrotoxicity. Ototoxic effects are at least
      in part a consequence of oxidative stress, and various antioxidants have been
      used to attenuate gentamicin-induced hair cell death and hearing loss. Here, a
      combination of nutrients previously shown to reduce oxidative stress in the hair
      cells and attenuate hearing loss after other insults was evaluated for potential
      protection against gentamicin-induced ototoxicity. Guinea pigs were maintained on
      a nutritionally complete standard laboratory animal diet or a diet supplemented
      with beta-carotene, vitamins C and E, and magnesium. Three diets with iterative
      increases in nutrient levels were screened; the final diet selected for study use
      was one that produced statistically reliable increases in plasma levels of
      vitamins C and E and magnesium. In two separate studies, significant decreases in
      gentamicin-induced hearing loss at frequencies including 12 kHz and below were
      observed, with less benefit at the higher frequencies. Consistent with the
      functional protection, robust protection of both the inner and outer hair cell
      populations was observed, with protection largely in the upper half of the
      cochlea. Protection was independently assessed in two different laboratories,
      using two different strains of guinea pigs. Additional in vitro tests did not
      reveal any decrease in antimicrobial activity with nutrient additives. Currently,
      there are no FDA-approved treatments for the prevention of gentamicin-induced
      ototoxicity. The current data provide a rationale for continued investigations
      regarding translation to human patients.

PMID- 24590395
TI  - Electronic tuning of Mo2(thioamidate)4 complexes through pi-system substituents
      and cis/trans isomerism.
AB  - We report an exploration of the coordination chemistry of a systematic series of
      cyclic thioamidate ligands with the quadruply-bonded Mo2(4+) core. In addition to
      the S and N donor atoms that bind to Mo, the ligands utilized in this study have
      an additional O or S atom in conjugation with the thioamidate pi system. The
      preparation of four new Mo2 complexes is described, and these compounds are
      characterized by X-ray crystallography, NMR and UV-vis spectroscopy,
      electrochemistry, and DFT calculations. These complexes provide a means to
      interrogate the electronics of Mo2(thioamidate)4 systems. Notably, we describe
      the first two examples of Mo2(thioamidate)4 complexes in their cis-2,2
      regioisomer. By varying the pi-system substituent and regioisomerism of these
      compounds, the electronics of the dimolybdenum core is shown to be altered with
      varying degrees of effect. Cyclic voltammetry results show that changing the pi
      system substituent from O to S results in an increase in the Mo2(4+/5+) oxidation
      potential by 170 mV. Changing the arrangement of ligands around the dimolybdenum
      core from trans-2,2 to cis-2,2 slightly weakens the metal-ligand bonds, raising
      the oxidation potential by a more modest 30-100 mV. MO diagrams of each compound
      derived from DFT calculations support these conclusions as well; the identity of
      the pi-system substituent alters the delta-delta* (HOMO-LUMO) gap by up to 0.4
      eV, whereas regioisomerism yields smaller changes in the electronic structure. 

PMID- 24590393
TI  - Poorer aerobic fitness relates to reduced integrity of multiple memory systems.
AB  - Epidemiological investigations have revealed increases in the prevalence of
      sedentary behaviors in industrialized societies. However, the implications of
      those lifestyle choices and related cardiorespiratory fitness levels for memory
      function are not well-understood. To determine the extent to which
      cardiorespiratory fitness relates to the integrity of multiple memory systems, a
      cross-sectional sample of young adults were tested over the course of 3 days in
      areas related to implicit memory, working memory, long-term memory, and aerobic
      fitness. Findings revealed an association between aerobic fitness and memory
      function such that individuals with lower cardiorespiratory fitness exhibited
      poorer implicit memory performance and poorer long-term memory retention. These
      data indicate that cardiorespiratory fitness may be important for the optimal
      function of neural networks underlying these memory systems. 

PMID- 24590394
TI  - Age-differential effects on updating cue information: evidence from event-related
      potentials.
AB  - Recent models on cognitive aging consider the ability to maintain and update
      context information to be a key source of age-related impairments in various
      cognitive tasks (Braver & Barch in Neuroscience & Biobehavioral Reviews, 26: 809
      817, 2002). Context updating has been investigated with a modified AX-continuous
      performance task by comparing performance and brain activity between context
      dependent trials (i.e., correct responses require updating of the preceding cue
      information) and context-independent trials (i.e., correct responses are
      independent of cue information). We used an event-related potential (ERP)
      approach to identify sources of age differences in context processing in the
      early and late processing of cue information. Our behavioral data showed longer
      latencies and higher error rates on context-dependent than on context-independent
      trials for older than for younger adults, suggesting age-related impairments in
      context updating. The ERP data revealed larger P3b amplitudes for context
      dependent than for context-independent trials only in younger adults. In
      contrast, in older adults, P3b amplitudes were more evenly distributed across the
      scalp and did not differ between context conditions. Interestingly, older but not
      younger adults were sensitive to changes of cue identity, as indicated by larger
      P3b amplitudes on cue-change than on cue-repeat trials, irrespective of the
      actual context condition. We also found a larger CNV on context-dependent than on
      context-independent trials, reflecting active maintenance of context information
      and response preparation. The age-differential effects in the P3b suggest that
      both younger and older adults were engaged in updating task-relevant information,
      but relied on different information: Whereas younger participants indeed relied
      on context cues to update and reconfigure the task settings, older adults relied
      on changes in cue identity, irrespective of context information. 

PMID- 24590396
TI  - Hematopoietic tumors of the female genital system: imaging features with
      pathologic correlation.
AB  - Various hematopoietic neoplasms can involve the female genital system. The most
      common hematological malignancy that involves the female genital system is
      lymphoma and secondary involvement is more common than primary genital lymphoma.
      Rarely, leukemic infiltration and extramedullary plasmacytomas of the female
      genital tract may also occur. Being infrequent, these lesions are commonly
      misdiagnosed radiologically. Therefore, understanding these malignancies of the
      female genital system and recognizing their imaging features are of utmost
      clinical importance. Although definitive diagnosis can be made only by
      histological analysis, imaging of these tumors plays an important role in
      detecting lesion extensions, guiding biopsies, staging disease, planning therapy,
      and detecting recurrence.

PMID- 24590397
TI  - Contrast enhanced ultrasound (CEUS) in the diagnosis of post-partum bilateral
      renal cortical necrosis: a case report and review of the literature.
AB  - Renal cortical necrosis is a rare condition with complex pathogenesis. There is
      no consensus over the best investigative modality for an initial diagnosis that
      is often in the context of acute renal failure. The applications of ultrasound
      contrast are ever growing, particularly with regard to the assessment of
      abdominal organs. Here, we present a case of post-partum bilateral renal cortical
      necrosis affecting bilateral native kidneys and the subsequent use of contrast
      enhanced ultrasound in confirming this diagnosis. The sonographic appearance was
      found to correlate with the patients' clinical presentation and other imaging
      findings. Secondarily, this allowed for appropriate and timely medical management
      and establishes the utility of ultrasound contrast in this clinical scenario.
      Contrast enhanced sonographic assessment should be considered early in patients
      with suspected renal vascular compromise. It is a safe, easy and efficacious
      investigative modality to stratify those patients with renal cortical necrosis
      from those with potentially reversible medical causes.

PMID- 24590398
TI  - Predictive value of dual-energy spectral computed tomographic imaging on the
      histological origin of carcinomas in the ampullary region.
AB  - PURPOSE: To investigate the value of dual-energy spectral computed tomographic
      imaging (DESCT) to predict the origin of carcinomas in the ampullary region.
      MATERIALS AND METHODS: Fifty-seven patients with suspected ampullary region
      carcinomas underwent DESCT prior to biopsy or surgery. Among those patients, 30
      were pancreatic adenocarcinomas, 11 were biliary adenocarcinomas, 16 were
      adenocarcinomas of the ampulla diagnosed by biopsy and/or pathological
      examination before or after surgical operation. We compared the CT spectral
      imaging features among the adenocarcinomas with the above-mentioned three
      different origins. RESULTS: Iodine concentration thresholds of 16.36, 21.86, and
      21.86 mg/mL yielded a sensitivity and specificity of 100% for distinguishing
      between common bile duct adenocarcinomas and pancreatic adenocarcinomas in the
      arterial phase (AP), portal venous phase (PP), and delayed phase (DP),
      respectively. Thresholds of 16.70, 24.33, and 26.43 mg/mL yielded a sensitivity
      and specificity of 100% for distinguishing between common bile duct
      adenocarcinomas and ampullary adenocarcinomas in the AP, PP, and DP,
      respectively. Iodine concentration thresholds of 16.66 and 17.78 mg/mL yielded a
      sensitivity and specificity of 100% for distinguishing between ampullary
      adenocarcinomas and pancreatic adenocarcinomas in the PP and DP, respectively.
      CONCLUSION: DESCT with multiple parameters can provide useful diagnostic
      information and may be used to predict the histological origin of carcinomas in
      the ampullary region.

PMID- 24590399
TI  - Aspidosperma species as sources of antimalarials. Part III. A review of
      traditional use and antimalarial activity.
AB  - Several plant species belonging to the genus Aspidosperma are traditionally used
      in Brazil and other Meso- and South American countries for the treatment of
      malaria and fevers. These traditional uses were motivation for this review. A
      literature survey completed for this review has identified scientific
      bibliographical references to the use of 24 Aspidosperma species to treat
      malaria/fevers and to 19 species that have had their extracts and/or alkaloids
      evaluated, with good results, for in vitro and/or in vivo antimalarial activity.
      Indole alkaloids are typical constituents of Aspidosperma species. However, only
      20 out of more than 200 known indole alkaloids isolated from this genus have been
      assayed for antimalarial activity. These data support the potential of
      Aspidosperma species as sources of antimalarials and the importance of research
      aimed at validating their use in the treatment of human malaria. 

PMID- 24590400
TI  - Flap endonuclease 1 is a promising candidate biomarker in gastric cancer and is
      involved in cell proliferation and apoptosis.
AB  - As a DNA repair protein, flap endonuclease 1 (FEN1), a structure-specific 5'
      nuclease, plays pivotal roles in the maturation of Okazaki fragments, long-patch
      base excision repair, restarting of stalled replication forks and telomere
      maintenance. FEN1 possesses 5' endonuclease, 5' exonuclease and gap-endonuclease
      activities, which render it an essential node in maintaining genome fidelity. The
      aim of this study was to investigate the association between the expression level
      of FEN1 and gastric cancer and to explore the role of FEN1 in carcinogenesis and
      the progression of gastric cancer. The mRNA and protein expression of FEN1 in 42
      matched pairs of human gastric tumor tissues and corresponding normal tissues
      were measured by semiquantitative reverse transcription-PCR and
      immunohistochemical staining. FEN1 expression was downregulated in the SGC-7901
      gastric cancer cells following transfection with siRNA targeting the FEN1 gene.
      Western blot analysis was used to evaluate the protein expression of FEN1 in SGC
      7901 human gastric cancer cells in order to verify the transfection efficiency of
      FEN1 siRNA. Moreover, cell proliferation was analyzed by MTS assay. The apoptosis
      of the cells was determined by flow cytometry. Our results revealed that FEN1 was
      overexpressed in gastric cancer in comparison to the corresponding normal gastric
      tissues (P<0.01). We further confirmed that FEN1 expression has a positive
      correlation with the degree of differentiation (P=0.027), lymphatic metastasis
      (P=0.001), tumor size (P=0.026) and TNM stage (P=0.020) of gastric cancer. A high
      FEN1 expression in SGC-7901 cells can be effectively downregulated by siRNA
      constructed to target the FEN1 gene. Moreover, the inhibition of FEN1 expression
      suppressed the proliferation and induced the apoptosis of SGC-7901 cells. Taken
      together, our results indicate that FEN1 may be a promising biomarker for the
      diagnosis of gastric cancer and individual therapy.

PMID- 24590402
TI  - Quality of life and brain tumors: what beyond the clinical burden?
AB  - This study analyzed the subjective facets of quality of life (QoL) and their
      relation to the type of brain tumor (BT) and phase of disease. Two hundred and
      ninety-one patients with pinealoblastoma, medulloblastoma, low-grade glioma,
      anaplastic astrocytoma, or glioblastoma were evaluated. With respect to 110
      healthy controls, patients in the phases of radiotherapy/chemotherapy, stable
      disease, or tumor recurrence were significantly more anxious and depressed
      compared with patients in the early postoperative period. All patients were
      impaired in mental flexibility and memory, with preservation of abstract
      reasoning. The Functional Living Index-Cancer (FLIC), previously validated in
      cancer and BT patients, yielded six subjective factors (disease perception,
      affective well-being, role and leisure, personal base, nausea, sharing). None of
      the FLIC factors were predicted by tumor type, which only related to the physical
      and cognitive performances and mood scores. Affective well-being, role and
      leisure, and sharing were predicted by the phase of disease. Personal base,
      including self-perception and confidence, was independent on tumor progression
      and treatment. To conclude, QoL encompasses different subjective aspects, which
      vary in relation to the phase of disease and clinical burden. However, some
      person-related facets appear independent on tumor progression and treatment,
      indicating individual resources. Knowing this may guide tailored interventions
      supporting QoL.

PMID- 24590404
TI  - Parkinson's disease with and without preceding essential tremor-similar
      phenotypes: a pilot study.
AB  - The aim of this pilot study was to compare clinical aspects of tremor-dominant
      Parkinson's disease (PD) patients with and without preceding essential tremor to
      identify characteristics of these two subgroups. Nineteen patients with diagnoses
      of both essential tremor (ET) and Parkinson's disease in comparison to 18
      patients with tremor-dominant Parkinson's disease without preceding tremor were
      investigated. The profile of several motor and non-motor symptoms, including
      cognitive dysfunction, depression, sleep alterations, olfaction changes and some
      autonomic symptoms, as well as imaging aspects obtained by transcranial
      sonography were compared between groups. Parkinson's patients with essential
      tremor scored higher in kinetic and postural tremor items (p < 0.05) and
      displayed an enlarged third ventricle on transcranial sonography (p = 0.010),
      which was not found in tremor-dominant Parkinson's disease patients. All other
      motor and non-motor symptoms could not distinguish between either study group.
      Neither group showed a distinct clinical profile related to non-motor symptoms or
      symptoms other than tremor-specific motor aspects. The fact that non-motor
      symptoms were similar in ET-PD gives rise to the hypothesis that also the
      prodromal phase of PD is similar in ET patients later developing classical PD
      compared to individuals developing PD without preceding ET. This hypothesis needs
      to be followed in prospective studies to verify whether the establishment of an
      ET subgroup with prodromal markers for PD is feasible.

PMID- 24590405
TI  - Sleep disorders in spinal and bulbar muscular atrophy (Kennedy's disease): a
      controlled polysomnographic and self-reported questionnaires study.
AB  - No data are available regarding the occurrence of sleep disorders in spinal and
      bulbar muscular atrophy (SBMA). We investigated the sleep-wake cycle in SBMA
      patients compared with healthy subjects. Nine SBMA outpatients and nine age
      matched and sex-matched healthy controls were evaluated. Subjective quality of
      sleep was assessed by means of the Pittsburgh Sleep Quality Index (PSQI). The
      Epworth Sleepiness Scale was used in order to evaluate excessive daytime
      sleepiness. All participants underwent a 48-h polysomnography followed by the
      multiple sleep latency test. Time in bed, total sleep time and sleep efficiency
      were significantly lower in SBMA than controls. Furthermore, the apnea-hypopnea
      index (AHI) was significantly higher in SBMA than controls. Obstructive sleep
      apnea (OSA: AHI >5/h) was evident in 6/9 patients (66.6 %). REM sleep without
      atonia was evident in three patients also affected by OSA and higher AHI in REM;
      2/9 (22.2 %) SBMA patients showed periodic limb movements in sleep. The global
      PSQI score was higher in SBMA versus controls. Sleep quality in SBMA is poorer
      than in controls. OSA is the most common sleep disorder in SBMA. The sleep
      impairment could be induced both by OSA or/and the neurodegenerative processes
      involving crucial areas regulating the sleep-wake cycle.

PMID- 24590406
TI  - Recent advances in epilepsy.
AB  - We have reviewed some of the important studies published within the last 18
      months that have advanced our understanding of the epilepsies, their aetiology
      and treatment. Clinical studies have revealed new insights into old themes
      including seizure prediction, mortality in epilepsy, febrile seizures and the
      pathophysiology of focal cortical dysplasias. The rapid advances in genetics and
      particularly whole exome sequencing have had an impact on our understanding of
      epileptic encephalopathies, and the aetiology of hippocampal sclerosis.
      Experimental research techniques such as viral vector gene delivery, optogenetics
      and cell based transplantation techniques have set the framework for novel
      approaches to the treatment of pharmacoresistant epilepsy. These few examples are
      indicative of the great strides that have recently been made in epilepsy
      research.

PMID- 24590407
TI  - Frequency and predictors of spontaneous hemorrhagic transformation in ischemic
      stroke and its association with prognosis.
AB  - Few prospective studies have examined the frequency, predictors and long-term
      outcomes of spontaneous hemorrhagic transformation (HT) in patients with ischemic
      stroke not receiving thrombolytic treatment. We prospectively enrolled a
      consecutive cohort of 407 patients with ischemic stroke who were admitted within
      one month of stroke onset. In patients who developed spontaneous HT, the area of
      the infarct and HT were examined by computed tomography (CT) or magnetic
      resonance imaging (MRI). Univariate analysis was used to correlate clinical
      characteristics with appearance of HT, then multivariate logistical regression
      was used to identify independent predictors of spontaneous HT and factors that
      predict 3-month prognosis of ischemic stroke. Spontaneous HT was observed in 50
      patients (12.3 %), comprising 33 cases (66 %) of hemorrhagic infarction, 17 (34
      %) of parenchymal hematoma, 32 (64 %) of non-symptomatic HT, and 18 (36 %) of
      symptomatic HT. In 40 % of HT cases, the condition was detected by CT or MRI
      within 4-7 days of symptom onset. Multivariate logistic regression identified
      atrial fibrillation (OR 4.88, 95 % CI 1.83-13.00, P = 0.002) and infarct area (OR
      4.48, 95 % CI 1.85-10.85, P = 0.001) as independent predictors of HT in ischemic
      stroke. Multivariate analysis also found that spontaneous HT was not
      independently associated with a worse 3-month prognosis for ischemic stroke (OR
      1.59, 95 % CI 0.38-6.69, P = 0.527). Spontaneous HT occurred in 12.3 % of our
      patients with ischemic stroke, and atrial fibrillation and large infarct area
      were independent predictors. Spontaneous HT was not an independent predictor of a
      worse 3-month prognosis for ischemic stroke.

PMID- 24590408
TI  - Atypical prosody in Asperger syndrome: perceptual and acoustic measurements.
AB  - It is known that individuals with Asperger syndrome (AS) may show no problems
      with regard to what is said (e.g., lexical content) but tend to have difficulties
      in how utterances are produced, i.e., they may show prosodic impairments. In the
      present study, we focus on the use of prosodic features to express grammatical
      meaning. Specifically, we explored the sentence type difference between
      statements and questions that is conveyed by intonation, using perceptual and
      acoustic measurements. Children aged 8 and 9 years with AS (n = 12) were matched
      according to age and nonverbal intelligence with typically developing peers (n =
      17). Although children with AS could produce categorically accurate prosodic
      patterns, their prosodic contours were perceived as odd by adult listeners, and
      acoustic measurements showed alterations in duration and pitch. Additionally,
      children with AS had greater variability in fundamental frequency contours
      compared to typically developing peers.

PMID- 24590409
TI  - The autism diagnostic observation schedule, module 4: revised algorithm and
      standardized severity scores.
AB  - The recently published Autism Diagnostic Observation Schedule, 2nd edition (ADOS
      2) includes revised diagnostic algorithms and standardized severity scores for
      modules used to assess younger children. A revised algorithm and severity scores
      are not yet available for Module 4, used with verbally fluent adults. The current
      study revises the Module 4 algorithm and calibrates raw overall and domain totals
      to provide metrics of autism spectrum disorder (ASD) symptom severity.
      Sensitivity and specificity of the revised Module 4 algorithm exceeded 80 % in
      the overall sample. Module 4 calibrated severity scores provide quantitative
      estimates of ASD symptom severity that are relatively independent of participant
      characteristics. These efforts increase comparability of ADOS scores across
      modules and should facilitate efforts to examine symptom trajectories from
      toddler to adulthood. 

PMID- 24590410
TI  - Contact burn due to a heated-wire breathing circuit.

PMID- 24590414
TI  - Is the phosphaethynolate anion, (OCP)(-), an ambident nucleophile? A
      spectroscopic and computational study.
AB  - The reactivity of Na(OCP) was investigated towards triorganyl compounds of the
      heavier group 14 elements (R3EX R = Ph or (i)Pr; E = Si, Ge, Sn, Pb; X = Cl,
      OTf). In the case of E = Si two constitutional isomers were formed and
      characterised in situ: R3Si-O-C[triple bond, length as m-dash]P is the kinetic
      and R3Si-P[double bond, length as m-dash]C[double bond, length as m-dash]O is the
      thermodynamic product, representing experimental evidence of the ambident
      character of the (OCP)(-) anion. Applying theoretical calculations and
      spectroscopic methods, the compound previously reported as (i)Pr3Si-O-C[triple
      bond, length as m-dash]P can now unambiguously be identified as (i)Pr3Si-P[double
      bond, length as m-dash]C[double bond, length as m-dash]O. The heavier analogues
      form exclusively the phosphaketene isomer R3E-P[double bond, length as m
      dash]C[double bond, length as m-dash]O (E = Ge, Sn, Pb). DFT calculations were
      performed to gain deeper insight into the bonding and thermodynamic stability of
      these compounds. 

PMID- 24590411
TI  - Isolation and identification of feline herpesvirus type 1 from a South China
      tiger in China.
AB  - In 2012, an FHV-1-like virus was isolated from a tiger that presented with
      clinical signs of sialorrhea, sneezing and purulent rhinorrhea. Isolation was
      performed with the FK81 cell line, and the virus was identified by PCR,
      transmission electron microscopy (TEM), and the phylogenetic analysis of the
      partial thymidine kinase (TK) and glycoprotein B (gB) genes. A total of 253 bp of
      the TK gene and 566 bp of the gB gene were amplified from the trachea of the
      tiger by PCR/RT-PCR method. Phylogenetic analysis showed that the isolate
      belonged to the same cluster with other FHV-1 strains obtained from GenBank.
      Herpes-like viruses with an envelope and diameters of approximately 200 nm were
      observed in the culture supernatants of FK81 cells inoculated with samples from
      the tiger. The FHV-1 infection was confirmed by an animal challenge experiment in
      a cat model. Our finding extends the host range of FHV-1 and has implications for
      FHV-1 infection and South China tiger conservation. 

PMID- 24590412
TI  - A population-level approach to promoting healthy child development and school
      success in low-income, urban neighborhoods: impact on parenting and child conduct
      problems.
AB  - Minority children living in disadvantaged neighborhoods are at high risk for
      school dropout, delinquency, and poor health, largely due to the negative impact
      of poverty and stress on parenting and child development. This study evaluated a
      population-level, family-centered, school-based intervention designed to promote
      learning, behavior, and health by strengthening parenting, classroom quality, and
      child self-regulation during early childhood. Ten schools in urban districts
      serving primarily low-income Black students were randomly assigned to
      intervention or a "pre-kindergarten education as usual" control condition.
      Intervention included a family program (a 13-week behavioral parenting
      intervention and concurrent group for children) and professional development for
      early childhood teachers. The majority (88 %) of the pre-kindergarten population
      (N = 1,050; age 4) enrolled in the trial, and nearly 60 % of parents in
      intervention schools participated in the family program. This study evaluated
      intervention impact on parenting (knowledge, positive behavior support, behavior
      management, involvement in early learning) and child conduct problems over a 2
      year period (end of kindergarten). Intent-to-treat analyses found intervention
      effects on parenting knowledge, positive behavior support, and teacher-rated
      parent involvement. For the highest-risk families, intervention also resulted in
      increased parent-rated involvement in early learning and decreased harsh and
      inconsistent behavior management. Among boys at high risk for problems based on
      baseline behavioral dysregulation (age 4, 23 % of sample), intervention led to
      lower rates of conduct problems at age 6. Family-centered intervention at the
      transition to school has potential to improve population health and break the
      cycle of disadvantage for low-income, minority families. 

PMID- 24590416
TI  - Importance of preclinical research in the development of neuroprotective
      strategies for ischemic stroke.
AB  - IMPORTANCE: Preclinical stroke research has had a remarkably low translational
      success rate, and the clinical need for novel neuroprotective therapeutics has
      gone largely unmet, especially in light of the severe underuse of thrombolysis in
      acute ischemic stroke. OBJECTIVE: In this review, we aim to provide a brief
      overview of the commonly used stroke models, their merits and shortcomings, and
      how these have contributed to translational failures. We review some recent
      developments in preclinical stroke, providing examples of how improved study
      quality and the use of novel methods can facilitate translation into the clinical
      setting. EVIDENCE REVIEW: This is a narrative review of ischemic stroke
      neuroprotection based on electronic database searches, references of previous
      publications, and personal libraries. FINDINGS: The stroke research community has
      not been complacent in its response to criticism: preclinical stroke studies now
      demonstrate considerable rigor, standardization, and emphasis on minimization of
      experimenter bias. In addition, numerous innovative methods and strategies are
      providing novel avenues for investigating neuroprotection, as well as more
      extensive characterization of established models. CONCLUSIONS AND RELEVANCE: The
      improvements in preclinical stroke models and methods will make stroke research a
      good example for preclinical medicine, in general, and will hopefully instill
      greater confidence in the clinical community regarding which compounds are worthy
      of further investigation in a clinical setting.

PMID- 24590418
TI  - Purposeful normalization when caring for husbands recovering from prostate
      cancer.
AB  - Despite a growing awareness that prostate cancer is a "couple's disease," the
      coping strategies, subjective distress, and emotional needs of partners are not
      adequately addressed. To better understand wives' experiences and processes they
      enact, we recruited 28 low-income Latinas caring for husbands recovering from
      prostatectomies to participate in interviews at three time points. Their
      narratives destabilize a common focus on physical side effects and an implicit
      bias toward men's reactions. We critically examine an overarching process of
      normalization, with underlying themes working both toward and against normality.
      We identified dissonance between detailed accounts of major lifestyle changes and
      professed normalization. We detail the women's purposeful methods to counteract
      negative impacts on their lives while seeking support externally. A better
      understanding of women's strategies and coping is critical to design
      interventions and education to both capitalize on partners' role in recovery
      while also addressing hidden causes of increased subjective distress. 

PMID- 24590419
TI  - Dissonance-based prevention of eating disorder risk factors in middle school
      girls: results from two pilot trials.
AB  - OBJECTIVE: Although several eating disorder prevention programs reduce eating
      disorder risk factors and symptoms for female high school and college students,
      few efficacious prevention programs exist for female middle school students,
      despite the fact that body image and eating disturbances often emerge then. Two
      pilot trials evaluated a new dissonance-based eating disorder prevention program
      for middle school girls with body image concerns. METHOD: Female middle school
      students with body dissatisfaction from two sites [Study 1: N = 81, M age = 12.1,
      standard deviation (SD) = 0.9; Study 2: N = 52, M age = 12.5, SD = 0.8] were
      randomized to a dissonance intervention (MS Body Project) or educational brochure
      control; Study 2 included a 3-month follow-up. RESULTS: Intervention participants
      showed significant post-test reductions in only one of the six variables with
      both Studies 1 and 2 (i.e., pressure to be thin and negative affect,
      respectively), though post-test effect sizes suggested medium reductions in
      eating disorder risk factors and symptoms (Study 1: M d = .40; Study 2: M d =
      .65); reductions at 3-month follow-up in Study 2 were not evident (M d = .19).
      CONCLUSIONS: Results suggest that this new middle school version of the Body
      Project is producing medium magnitude reductions in eating disorder risk factors
      at post-test but that effects are showing limited persistence. Continued
      refinement and evaluation of this intervention appears warranted to develop more
      effective prevention programs for this age group.

PMID- 24590421
TI  - Platelet-cancer interactions.
AB  - Platelets play a crucial role in the pathophysiological processes of hemostasis
      and thrombosis. Increasing evidence indicates that they fulfill much broader
      roles in balancing health and disease. The presence of tumor cells affects
      platelets both numerically, through a wide variety of mediators and cytokines, or
      functionally through tumor cell-induced platelet activation, the first step
      toward cancer-induced thrombosis. This induction results from signaling events
      through the different platelet receptors, or may be cytokine-mediated.
      Reciprocally, upon activation, the platelets will release a myriad of growth
      factors from their dense and alpha-granules and peroxisomes; these will directly
      impact tumor growth, tethering, and spread. A similar cross-talk is initiated
      between tumor microvesicles stimulating the platelets and platelet
      microparticles, promoting both thrombosis and tumor growth. A vicious loop of
      activation thereafter takes place. Platelets directly and indirectly promote
      tumor growth, and enable a molecular mimicry coating the malignant growth and
      allowing metastasizing cells to escape T-cell-mediated immunity and natural
      killer cell surveillance. Breaking this vicious activation loop with nonspecific
      platelet inhibitors, such as aspirin, or by targeting specific sites on the
      activation cascade may offer a mean to reduce both the risks of development and
      progression of cancer and the risk of thrombosis. 

PMID- 24590422
TI  - The unique hemostatic dysfunction in acute promyelocytic leukemia.
AB  - The hemostatic abnormalities seen in acute promyelocytic leukemia (APL) are
      unique and account for much of the morbidity and mortality of this disorder.
      Almost all patients present at diagnosis with laboratory findings of
      intravascular coagulation along with increased fibrinolysis. This unusual
      combination is correlated to the clinical manifestations with high risk of both
      bleeding and thrombosis. Recent studies have revealed that the leukemic
      promyelocytes in APL express increased amounts of tissue factor as well as
      elements of the fibrinolytic system, including tissue plasminogen activator,
      annexin A2, and plasminogen activator inhibitor type 1. These changes are
      responsive to differentiation therapy with all-trans-retinoic acid (ATRA) or with
      arsenic trioxide (ATO). Despite a dramatic reduction in mortality seen since the
      introduction of differentiation therapy with ATRA or with ATO, a large number of
      deaths still occur before complete remission is achieved. The early deaths are
      mostly attributable to the presenting coagulopathy. The prevention and management
      of this hemostatic abnormality have thus far been unsuccessful and remain a
      challenge to bring about a higher cure rate for this disease. 

PMID- 24590420
TI  - NETosis: a new factor in tumor progression and cancer-associated thrombosis.
AB  - Neutrophils have long been known as innate immune cells that phagocytose and kill
      pathogens and mount inflammatory responses protecting the host from infection. In
      the past decades, new aspects of neutrophils have emerged unmasking their
      importance not only in inflammation but also in many pathological conditions
      including thrombosis and cancer. The 2004 discovery that neutrophils, upon strong
      activation, release decondensed chromatin to form neutrophil extracellular traps
      (NETs), has unveiled new avenues of research. Here, we review current knowledge
      regarding NETs in thrombosis, with a special focus on cancer-associated
      thrombosis as well as their potential role in cancer growth and metastasis. We
      discuss the prospective use of NET-specific biomarkers, such as citrullinated
      histone H3 and NET inhibitors, as tools to anticipate and fight cancer-associated
      thrombosis. We propose that the rapid developments in the field of NETosis may
      provide new targets to combat the thrombotic consequences of cancer and perhaps
      even help to contain the disease itself. 

PMID- 24590423
TI  - The effect of the intermolecular potential formulation on the state-selected
      energy exchange rate coefficients in N2-N2 collisions.
AB  - The rate coefficients for N2-N2 collision-induced vibrational energy exchange
      (important for the enhancement of several modern innovative technologies) have
      been computed over a wide range of temperature. Potential energy surfaces based
      on different formulations of the intramolecular and intermolecular components of
      the interaction have been used to compute quasiclassically and semiclassically
      some vibrational to vibrational energy transfer rate coefficients. Related
      outcomes have been rationalized in terms of state-to-state probabilities and
      cross sections for quasi-resonant transitions and deexcitations from the first
      excited vibrational level (for which experimental information are available). On
      this ground, it has been possible to spot critical differences on the vibrational
      energy exchange mechanisms supported by the different surfaces (mainly by their
      intermolecular components) in the low collision energy regime, though still
      effective for temperatures as high as 10,000 K. It was found, in particular, that
      the most recently proposed intermolecular potential becomes the most effective in
      promoting vibrational energy exchange near threshold temperatures and has a
      behavior opposite to the previously proposed one when varying the coupling of
      vibration with the other degrees of freedom.

PMID- 24590424
TI  - Continuous symmetry measures for complex symmetry group.
AB  - Symmetry is a fundamental property of nature, used extensively in physics,
      chemistry, and biology. The Continuous symmetry measures (CSM) is a method for
      estimating the deviation of a given system from having a certain perfect
      symmetry, which enables us to formulate quantitative relation between symmetry
      and other physical properties. Analytical procedures for calculating the CSM of
      all simple cyclic point groups are available for several years. Here, we present
      a methodology for calculating the CSM of any complex point group, including the
      dihedral, tetrahedral, octahedral, and icosahedral symmetry groups. We present
      the method and analyze its performances and errors. We also introduce an
      analytical method for calculating the CSM of the linear symmetry groups. As an
      example, we apply these methods for examining the symmetry of water, the symmetry
      maps of AB4 complexes, and the symmetry of several Lennard-Jones clusters.

PMID- 24590428
TI  - Context-specific prospective-memory processing: evidence for flexible attention
      allocation adjustments after intention encoding.
AB  - Prospective memory (PM) is remembering to fulfill intentions in the future.
      Interference of unfulfilled intentions with ongoing activities reflects the
      allocation of attention to the PM task. Prior research has shown that, when
      people know in which specific context PM cues will occur, attention allocation is
      adaptive, with slower responses in the PM-relevant context. We examined whether
      people flexibly adjust their attention allocation when the PM-context association
      is unknown at intention encoding and must be learned on-task. Different stimulus
      shapes represented contexts in an ongoing task, with PM cues only occurring in
      trials with one specific shape. Participants informed about the PM-relevant shape
      responded more slowly on trials with this shape. Participants instructed that
      only one, unspecified shape was PM-relevant learned the PM-context association
      and also allocated attention flexibly, depending on context relevance. However,
      participants with no context-related information at intention encoding failed to
      learn the PM-context association, resulting in inflexible attention allocation
      and poorer PM performance. The present study provides evidence that people can
      flexibly update their attention-allocation policy, and thereby optimize their PM
      performance after initial intention encoding, but self-guided learning of
      intention-context associations appears to be limited.

PMID- 24590430
TI  - When looks are deceiving--the challenge facing embryo quality prognosticators.

PMID- 24590429
TI  - PVA gel as a potential adhesion barrier: a safety study in a large animal model
      of intestinal surgery.
AB  - BACKGROUND: Intra-abdominal adhesions following surgery are a major source of
      morbidity and mortality including abdominal pain and small bowel obstruction.
      This study evaluated the safety of PVA gel (polyvinyl alcohol and
      carboxymethylated cellulose gel) on intestinal anastomoses and its potential
      effectiveness in preventing adhesions in a clinically relevant large animal
      model. METHODS: Experiments were performed in a pig model with median laparotomy
      and intestinal anastomosis following small bowel resection. The primary endpoint
      was the safety of PVA on small intestinal anastomoses. We also measured the
      incidence of postoperative adhesions in PVA vs. control groups: group A (eight
      pigs): stapled anastomosis with PVA gel compared to group B (eight pigs), which
      had no PVA gel; group C (eight pigs): hand-sewn anastomosis with PVA gel compared
      to group B (eight pigs), which had no anti-adhesive barrier. Animals were
      sacrificed 14 days after surgery and analyzed. RESULTS: All anastomoses had a
      patent lumen without any stenosis. No anastomoses leaked at an intraluminal
      pressure of 40 cmH2O. Thus, anastomoses healed very well in both groups,
      regardless of whether PVA was administered. PVA-treated animals, however, had
      significantly fewer adhesions in the area of stapled anastomoses. The hand-sewn
      PVA group also had weaker adhesions and trended towards fewer adhesions to
      adjacent organs. CONCLUSION: These results suggest that PVA gel does not
      jeopardize the integrity of intestinal anastomoses. However, larger trials are
      needed to investigate the potential of PVA gel to prevent adhesions in
      gastrointestinal surgery.

PMID- 24590431
TI  - Cost effectiveness of routine laparoscopic ultrasound for assessment of
      resectability of gallbladder cancer.
AB  - BACKGROUND: In addition to a diagnostic laparoscopy (DL), a routine laparoscopic
      ultrasound (LUS) has been proposed to identify undetected hepatic metastases
      and/or anatomically advanced disease in patients with T2 or higher gall bladder
      cancer (GBC) patients planned for surgical resection. It was hypothesized that a
      routine LUS is not a cost-effective strategy for these patients. METHODS:
      Decision tree modeling was undertaken to compare DL-LUS vs. DL at the time of
      definitive resection of GBC (with no prior cholecystectomy). Costs in US dollars
      (payer's perspective), quality-adjusted life weeks (QALWs), and incremental cost
      effectiveness ratios (ICER) were calculated (horizon: 6 weeks, willingness-to
      pay: $1,000/QALW or $50,000/QALY). RESULTS: DL-LUS was cost effective at the base
      case scenario (costs: $30,838 for DL vs. $30,791 for DL-LUS and effectiveness
      3.81 QALWs DL vs. 3.82 QALW DL-LUS), resulting in a cost reduction of $9,220 per
      quality-adjusted life week gained (or $479,469 per QALY). DL-LUS became less cost
      effective as the cost of ultrasound increased or the probability of exclusion
      from resection decreased. CONCLUSIONS: Routine LUS with DL for the assessment of
      resectability and exclusion of metastases is cost effective for patients with
      GBC. Until improvements in preoperative imaging occur to decrease the probability
      of exclusion, this appears to be a feasible strategy.

PMID- 24590432
TI  - Laparoscopic spleen-preserving no. 10 lymph node dissection for advanced proximal
      gastric cancer using a left approach.
AB  - BACKGROUND: We developed a novel procedure for spleen-preserving No. 10 lymph
      node (LN) dissection, which is difficult and advocates for patients with advanced
      proximal gastric cancer, except those with direct tumor extension to the spleen
      or definite LN metastasis at the splenic hilum. METHODS: The surgeon reveals the
      splenic vessels (SVs), and the assistant pulls up the lymphatic fatty tissue on
      the surface of the lower lobar vessels of the spleen (LLVSs). The surgeon then
      exposes the left gastroepiploic vessels (LGEVs), completely separating the LLVSs
      from the LGEV roots. After tracking the SV termini, the No. 11d LNs are carefully
      dissected and the upper lobar vessels of the spleen are exposed from their roots
      to the upper pole of the spleen. During this process, 2-4 branches of the short
      gastric vessels are skeletonized and divided at their roots. The LNs behind the
      SVs in front of Gerota's fascia are then dissected. The above procedure was
      performed on 118 consecutive patients with stage cT2-3 disease. RESULTS: Mean
      operation time was 20.4 +/- 6.0 min (range 13-41 min), mean blood loss was 13.6
      +/- 4.0 ml (range 10-40 ml), and mean times to first flatus, fluid diet, and soft
      diet were 3.3 +/- 1.2 days (range 2-8 days), 4.8 +/- 1.6 days (range 3-14 days),
      and 8.1 +/- 4.1 days (range 6-20 days), respectively. A mean 44.6 +/- 17.3 LNs
      (range 22-103) were retrieved, including a mean 3.0 +/- 2.4 (range 0-11) splenic
      hilar area LNs. At a median follow-up of 9 months, no patients had died or
      experienced recurrent or metastatic disease. CONCLUSIONS: This procedure is
      feasible and simplifies complicated laparoscopic No. 10 LN dissection.

PMID- 24590433
TI  - External validation of online predictive models for prediction of cancer-specific
      mortality and all-cause mortality in patients with urothelial carcinoma of the
      urinary bladder.
AB  - PURPOSE: The objective of the study was to validate the previously reported
      lookup Table and Bladder Cancer Research Consortium (BCRC) nomogram in predicting
      cancer-specific mortality (CSM) and all-cause mortality (ACM) after radical
      cystectomy using an external cohort from South Korea. METHODS: The study
      comprised 409 patients. Discrimination was quantified with the concordance index.
      The relationship between the model-derived and actual CSM and ACM was graphically
      explored within calibration plots. Clinical net benefit was evaluated by decision
      curve analysis. RESULTS: Of the 409 patients, 147 (35.9 %) had died from various
      causes. One hundred two deaths were attributable to bladder cancer. For CSM at 5
      years, the bootstrap-corrected concordance indices of the American Joint
      Committee on Cancer (AJCC) staging system, lookup Table, and BCRC nomogram were
      71.8 % (95 % confidence interval [CI] 66.9-76.5), 73.0 % (95 % CI 67.9-78.0), and
      76.2 % (95 % CI 71.6-80.9), respectively. For ACM at the same time point, the
      discrimination accuracies of these models were 70.7 % (95 % CI 66.7-74.6), 72.8 %
      (95 % CI 68.5-76.9), and 76.2 % (95 % CI 72.3-80.2), respectively. The
      calibration plots tended to exaggerate both survival outcomes in all models. When
      compared to the lookup Table as well as the AJCC staging system, the BCRC
      nomogram performed well across a wide range of threshold probabilities using
      decision curve analysis. CONCLUSIONS: The BCRC nomogram was characterized by
      higher accuracy and larger potential clinical benefit compared to the lookup
      Table. However, there is a great need for additional models that consider
      outcomes of patients for whom the existing models do not apply.

PMID- 24590434
TI  - Postgastrectomy Syndrome Assessment Scale (PGSAS)-45 and changes in body weight
      are useful tools for evaluation of reconstruction methods following distal
      gastrectomy.
AB  - BACKGROUND: Billroth-I (BI) and Roux-en-Y (RY) are well-known reconstruction
      methods that are conducted following distal gastrectomy. However, the relative
      merits of these 2 methods are not well documented. The newly developed
      Postgastrectomy Syndrome Assessment Scale (PGSAS)-45 is an integrated
      questionnaire consisting of 45 items, including 8 items from the 8-Item Short
      Form Health Survey (SF-8), 15 items from the Gastrointestinal Symptom Rating
      Scale, and 22 items selected by gastric surgeons. Postoperative QOL ratings were
      evaluated for each reconstruction method using PGSAS-45. METHODS: The PGSAS-45
      questionnaire was distributed to 2,922 patients who underwent gastrectomies at 52
      medical institutions. Among the questionnaires distributed, 2520 (86 %) were
      retrieved and 2368 (81 %) met eligibility requirements. Statistical analyses were
      conducted to compare 1,384 of the eligible questionnaires, including responses
      from patients who underwent BI (n = 909) and RY (n = 475) procedures. RESULTS: BI
      procedures were associated with significantly longer postoperative periods, a
      significantly greater size of gastric remnants, and a higher frequency of
      laparoscopic approaches and celiac branch preservation. Postoperative QOL
      analysis indicated that BI procedures resulted in significantly lower
      postoperative weight loss and significantly higher esophageal reflux symptoms
      than RY procedures. There was no significant difference between the two groups on
      other outcome measures. CONCLUSIONS: Although weight loss was significantly lower
      following BI procedures, esophageal reflux symptoms were significantly higher.
      Either BI or RY procedures may be recommended based on the individual patient's
      condition after distal gastrectomy. The newly developed QOL questionnaire, PGSAS
      45 and changes in body weight proved useful for evaluation of QOL following
      gastrectomy.

PMID- 24590435
TI  - Survival impact of lymphadenectomy stratified by nodal metastatic probability in
      endometrial cancer.
AB  - BACKGROUND: Our objective was to identify a subgroup of patients with early-stage
      endometrial cancer in whom lymphadenectomy was associated with enhanced survival
      based on the stratification of lymph node (LN) metastasis probability provided by
      a previously developed nomogram. METHODS: Data from the Surveillance,
      Epidemiology, and End Results database for 66,210 patients with histologically
      proven endometrial cancer were analyzed. For each patient, the LN metastasis
      probability according to the previously developed nomogram was calculated.
      Patients were clustered into quintiles according to their LN metastasis
      probability. The cancer related survival in each quintile group was calculated
      using Kaplan-Meier analysis and compared based on whether patients underwent
      lymphadenectomy. RESULTS: Except for the second quintile group, the specific
      survival rate systematically decreased when the predicted LN probability
      increased. In the five quintile groups, the 5-year specific survival rate was
      significantly higher in the patients who did not undergo lymphadenectomy compared
      with those who underwent lymphadenectomy and had >= 10 or <10 LNs removed.
      CONCLUSIONS: Our results suggest the pejorative outcome associated with a higher
      risk of LN metastasis is not counterbalanced by the lymphadenectomy.

PMID- 24590436
TI  - Technique selection of bricker or wallace ureteroileal anastomosis in ileal
      conduit urinary diversion: a strategy based on patient characteristics.
AB  - OBJECTIVES: This study was designed to establish an individualized selection
      strategy for the two most common types of ureteroenteric anastomotic techniques
      (Bricker and Wallace anastomosis) used in ileal conduit (IC) diversion. METHODS:
      Patients who underwent IC diversion after radical cystectomy for transitional
      cell carcinoma between January 2009 and December 2011 were prospectively
      collected. The choice of anastomosis type (Bricker vs. Wallace) was successively
      based on tumor characteristics, ureteral anomalies, and ureteral length after
      retrosigmoidal tunneling. RESULTS: Ninety-nine patients were enrolled in the
      final study. Fifty-three patients underwent Bricker anastomosis, and 46 underwent
      Wallace anastomosis. Ureteral stricture developed in 6 (6.1 %) patients and the
      overall stricture rate for all ureters was 3.1 % (6/196). Strictures occurred at
      an average of 13.3 months after surgery and were predominately located in the
      left ureter (66.7 %, 4/6). The difference in the ureter stricture rates between
      the two groups was not statistically significant: 3.8 % (4/104) and 2.2 % (2/92)
      for Bricker and Wallace, respectively (p = 0.686). There were no significant
      differences in age, sex, body mass index (BMI), prevalence of pelvic radiation
      therapy, length of stay, follow-up time, or time to stricture between the two
      techniques. Patients in whom stricture developed had a significantly higher mean
      BMI compared with those without stricture (25.2 vs. 23.3 kg/m(2), respectively; p
      = 0.008). CONCLUSIONS: Our preliminary outcomes demonstrate that this selection
      strategy of Bricker vs. Wallace anastomosis seems to be clinically reliable,
      providing an acceptable low ureteral stricture rate of 3.1 %. However, the
      potential advantage for oncologic control of this strategy is needed to further
      confirm.

PMID- 24590437
TI  - Product analysis and initial reliability testing of the total mesorectal excision
      quality assessment instrument.
AB  - BACKGROUND: Product analysis of rectal cancer resection specimens before specimen
      fixation may provide an immediate and relevant evaluation of surgical
      performance. We tested the interrater reliability (IRR) of a product analysis
      tool called the Total Mesorectal Excision-Quality Assessment Instrument (TME-QA).
      METHODS: Participants included two gold standard raters, five pathology
      assistants, and eight pathologists. Domains of the TME-QA reflect total
      mesorectal excision principles including: (1) completeness of mesorectal margin;
      (2) completeness of mesorectum; (3) coning of distal mesorectum; (4) physical
      defects; and (5) overall specimen quality. Specimens were scored independently.
      We used the generalizability theory to assess the tool's internal consistency and
      IRR. RESULTS: There were 39 specimens and 120 ratings. Mean overall specimen
      quality scores for the gold standard raters, pathologists, and assistants were
      4.43, 4.43, and 4.50, respectively (p > 0.85). IRR for the first nine items was
      0.68 for the full sample, 0.62 for assistants alone, 0.63 for pathologists alone,
      and 0.74 for gold standard raters alone. IRR for the item overall specimen
      quality was 0.67 for the full sample, 0.45 for assistants, 0.80 for pathologists,
      and 0.86 for gold standard raters. IRR increased for all groups when scores were
      averaged across two raters. CONCLUSIONS: Assessment of surgical specimens using
      the TME-QA may provide rapid and relevant feedback to surgeons about their
      technical performance. Our results show good internal consistency and IRR when
      the TME-QA is used by pathologists. However, for pathology assistants, multiple
      ratings with the averaging of scores may be needed.

PMID- 24590438
TI  - Dinuclear Ru-aqua complexes for selective epoxidation catalysis based on
      supramolecular substrate orientation effects.
AB  - Ru-aqua complex {[Ru(II)(trpy)(H2O)]2(MU-pyr-dc)}(+) is a powerful epoxidation
      catalyst for a wide range of linear and cyclic alkenes. High turnover numbers
      (TNs), up to 17000, and turnover frequencies (TOF), up to 24120 h(-1) (6.7 s(
      1)), have been obtained using PhIO as oxidant. This species presents an
      outstanding stereospecificity for both cis and trans olefins towards the
      formation of their corresponding cis and trans epoxides. In addition, it shows
      different reactivity to cis and trans olefins due to a substrate orientation
      supramolecular effect transmitted by its ligand scaffold. This effect together
      with the impressive reaction rates are rationalized using electrochemical
      techniques and DFT calculations.

PMID- 24590439
TI  - Beyond the proteome: Mass Spectrometry Special Interest Group (MS-SIG) at
      ISMB/ECCB 2013.

PMID- 24590440
TI  - Tospovirus ambisense genomic RNA segments use almost complete repertoire of
      stable tetraloops in the intergenic region.
AB  - The intergenic regions of the ambisense RNA segments of viruses from the
      Tospovirus genus form large extended RNA structures that regulate virus
      replication. Using comparative structure analysis, we show the presence of
      conserved alternative conformations at the apical parts of these structures. In
      one conformation, a branched Y-shape, the 5'-proximal hairpin arms are mostly
      capped by exceptionally stable tetraloop motifs. The tetraloop hairpins are
      folded in both virus and virus-complementary sense RNAs, and different tetraloops
      can functionally replace each other. Folding simulations show that the branched Y
      shape structures can undergo a conformational transition to alternative extended
      rod-like conformations. Functional importance of both alternatives is supported
      by nucleotide covariations. The balanced equilibrium between alternative
      structures is evidenced by native gel electrophoresis of mutant RNA transcripts
      with shifted equilibria. The tetraloops play a role in the stability and dynamics
      of structures but may also be recognized by proteins involved in translation
      and/or replication.

PMID- 24590441
TI  - Protein fold recognition using geometric kernel data fusion.
AB  - MOTIVATION: Various approaches based on features extracted from protein sequences
      and often machine learning methods have been used in the prediction of protein
      folds. Finding an efficient technique for integrating these different protein
      features has received increasing attention. In particular, kernel methods are an
      interesting class of techniques for integrating heterogeneous data. Various
      methods have been proposed to fuse multiple kernels. Most techniques for multiple
      kernel learning focus on learning a convex linear combination of base kernels. In
      addition to the limitation of linear combinations, working with such approaches
      could cause a loss of potentially useful information. RESULTS: We design several
      techniques to combine kernel matrices by taking more involved, geometry inspired
      means of these matrices instead of convex linear combinations. We consider
      various sequence-based protein features including information extracted directly
      from position-specific scoring matrices and local sequence alignment. We evaluate
      our methods for classification on the SCOP PDB-40D benchmark dataset for protein
      fold recognition. The best overall accuracy on the protein fold recognition test
      set obtained by our methods is ~ 86.7%. This is an improvement over the results
      of the best existing approach. Moreover, our computational model has been
      developed by incorporating the functional domain composition of proteins through
      a hybridization model. It is observed that by using our proposed hybridization
      model, the protein fold recognition accuracy is further improved to 89.30%.
      Furthermore, we investigate the performance of our approach on the protein remote
      homology detection problem by fusing multiple string kernels. AVAILABILITY AND
      IMPLEMENTATION: The MATLAB code used for our proposed geometric kernel fusion
      frameworks are publicly available at
      http://people.cs.kuleuven.be/~raf.vandebril/homepage/software/geomean.php?menu=5/

PMID- 24590442
TI  - BicOverlapper 2.0: visual analysis for gene expression.
AB  - MOTIVATION: Systems biology demands the use of several point of views to get a
      more comprehensive understanding of biological problems. This usually leads to
      take into account different data regarding the problem at hand, but it also has
      to do with using different perspectives of the same data. This multifaceted
      aspect of systems biology often requires the use of several tools, and it is
      often hard to get a seamless integration of all of them, which would help the
      analyst to have an interactive discourse with the data. RESULTS: Focusing on
      expression profiling, BicOverlapper 2.0 visualizes the most relevant aspects of
      the analysis, including expression data, profiling analysis results and
      functional annotation. It also integrates several state-of-the-art numerical
      methods, such as differential expression analysis, gene set enrichment or
      biclustering. AVAILABILITY AND IMPLEMENTATION: BicOverlapper 2.0 is available at:
      http://vis.usal.es/bicoverlapper2

PMID- 24590443
TI  - Challenges in RNA virus bioinformatics.
AB  - MOTIVATION: Computer-assisted studies of structure, function and evolution of
      viruses remains a neglected area of research. The attention of bioinformaticians
      to this interesting and challenging field is far from commensurate with its
      medical and biotechnological importance. It is telling that out of >200 talks
      held at ISMB 2013, the largest international bioinformatics conference, only one
      presentation explicitly dealt with viruses. In contrast to many broad,
      established and well-organized bioinformatics communities (e.g. structural
      genomics, ontologies, next-generation sequencing, expression analysis), research
      groups focusing on viruses can probably be counted on the fingers of two hands.
      RESULTS: The purpose of this review is to increase awareness among bioinformatics
      researchers about the pressing needs and unsolved problems of computational
      virology. We focus primarily on RNA viruses that pose problems to many standard
      bioinformatics analyses owing to their compact genome organization, fast mutation
      rate and low evolutionary conservation. We provide an overview of tools and
      algorithms for handling viral sequencing data, detecting functionally important
      RNA structures, classifying viral proteins into families and investigating the
      origin and evolution of viruses.

PMID- 24590444
TI  - The automated function prediction SIG looks back at 2013 and prepares for 2014.

PMID- 24590445
TI  - Effects of chlorpyrifos and endosulfan on different life stages of the freshwater
      burrowing crab Zilchiopsis collastinensis P.: protective role of chorion.
AB  - The lethality (LC50) of endosulfan and chlorpyrifos is higher in adults (1990 and
      156.78 MUg/L respectively) than in embryos (95380 and 1242.54 MUg/L respectively)
      of the crab Zilchiopsis collastinensis. The thickened embryonic coat of the
      freshwater species might isolate the embryo inside the egg, reducing the
      toxicity. Sublethal concentrations of chlorpyrifos and endosulfan caused an
      increase in hatching time and a decrease in effective hatching (p < 0.05), and
      only the control crabs survived until the first molt cycle. The effects of long
      term exposure should be evaluated in the offspring in addition to the acute
      toxicity.

PMID- 24590446
TI  - Correlation of MT levels in livers and gills with heavy metals in wild tilapia
      (Oreochromis mossambicus) from the Klang River, Malaysia.
AB  - Metallothionein (MT) concentrations in gill and liver tissues of Oreochromis
      mossambicus were determined to assess biological response of fish to levels of
      some metals. Metal concentrations in gill and liver tissues of O. mossambicus
      ranged from 0.6 to 2.6 for Cd, 16 to 52 for Zn, 0.5 to 17 for Cu and 2 to 67 for
      T-Hg (all in MUg/g wet weight, except for T-Hg in ng/g wet weight). Accumulation
      of Cd, Zn, Cu and Hg (MUg/g wet weight) in the liver and gills of O. mossambicus
      were in the order of liver > gills. The concentrations of Cd, Zn, Cu and Hg in
      fish tissues were correlated with MT content. The increases in MT levels from the
      reference area Puchong Tengah compared to the polluted area Kampung Seri Kenangan
      were 3.4- and 3.8-fold for gills and livers, respectively. The results indicate
      that MT concentrations were tissue-specific, with the highest levels in the
      liver. Therefore, the liver can act as a tissue indicator in O. mossambicus in
      the study area.

PMID- 24590447
TI  - Anterior corpectomy and fusion to C2 for cervical myelopathy: clinical results
      and complications.
AB  - PURPOSE: Anterior cervical corpectomy and fusion (ACCF) to C2 (ACCF-C2) for
      multilevel lesions is a challenging procedure that is indicated for massive
      ossification of the posterior longitudinal ligament (OPLL) extending to C2 or
      stenosis at the upper cervical region accompanied by kyphosis. However, there is
      little information on the effectiveness of and complications related to ACCF-C2.
      The purpose of this study was to investigate the overall surgical results and
      postoperative complications of ACCF-C2 for cervical myelopathy. METHODS: Sixteen
      patients who underwent ACCF-C2 for OPLL and cervical spondylotic myelopathy were
      evaluated. An iliac bone or a fibular strut was grafted using a cervical plate.
      The mean fusion level was 3.8, and the mean follow-up period was 36 months.
      Patients' charts, clinical results assessed using the Japanese Orthopedic
      Association (JOA) scale, and radiographs were retrospectively reviewed. RESULTS:
      The average preoperative JOA score was 11.5 +/- 3.5, and improved significantly
      to 13.1 +/- 3.2 at 24 months after surgery (P < 0.01). The postoperative cervical
      alignment was significantly improved at the last follow-up (P < 0.05). Seven
      patients experienced complications, including neurological complications in
      three, graft-related complications in three, cerebrospinal fluid leakage in two,
      late retropharyngeal perforation in one, and dysphasia in one. Three of 16
      patients experienced upper airway obstruction in this series, and 2 of 473
      patients who underwent anterior cervical decompression and fusion at lower levels
      in the same period (P < 0.001). CONCLUSIONS: ACCF-C2 is effective for massive
      OPLL and stenosis accompanied by kyphosis. To avoid complications, skilled
      decompression and bone grafting technique are necessary, and delayed extubation
      for upper airway obstruction is preferable.

PMID- 24590448
TI  - Medicare coverage of investigational devices: the troubled path forward for deep
      brain stimulation.

PMID- 24590449
TI  - Reply: dystonia after severe head injuries.

PMID- 24590451
TI  - Trans-rectus sheath extra-peritoneal procedure (TREPP) for inguinal hernia: the
      first 1,000 patients.

PMID- 24590450
TI  - Long-term results of the paraesophagogastric devascularization with or without
      esophageal transection: which is more suitable for variceal bleeding?
AB  - BACKGROUND: It has been reported that the paraesophagogastric devascularization
      with esophageal transection procedure, also known as the modified Sugiura
      procedure, was effective in the treatment of variceal bleeding. However, it was
      not widely accepted by other surgeons because of the high rate of rebleeding,
      complications, and mortality. To discover the effects of the paraesophagogastric
      devascularization procedure and the modified Sugiura procedure, we
      retrospectively analyzed the outcomes of these two procedures. MATERIALS AND
      METHODS: During January 1990 and December 2009, 278 patients with variceal
      bleeding underwent devascularization after failed pharmacotherapy and
      endotherapy. In these 278 patients, 180 underwent paraesophagogastric
      devascularization without esophageal transection (group I), and the other 98
      patients were subjected to the modified Sugiura procedure (group II). RESULTS:
      Postoperative mortality was 7.2% in group I, and 9.2% in group II (P = 0.563).
      The postoperative rebleeding rate in the two groups was 2.2 and 3.1%,
      respectively (P = 0.474). After a mean follow-up of 67.9 +/- 37.3 months and 67.4
      +/- 44.6 months, respectively, esophageal transaction-related morbidity (leak,
      bleeding, and stricture) was 8.2% (8/98) in group II and 0% (0/180) in group I (P
      < 0.001). The overall rebleeding rate was 27% (41/152) in group I, and 27.2%
      (22/81) in group II (P = 0.976). The overall mortality was 28.3% (43/152) in
      group I, and 28.4% (23/81) in group II (P = 0.986). CONCLUSIONS: In the
      management of variceal bleeding, paraesophagogastric devascularization without
      esophageal transection is as effective and safe as devascularization with
      esophageal transaction, but with less esophageal transection-related morbidity.

PMID- 24590452
TI  - Active and passive cigarette smoking and breast cancer risk: results from the
      EPIC cohort.
AB  - Recent cohort studies suggest that increased breast cancer risks were associated
      with longer smoking duration, higher pack-years and a dose-response relationship
      with increasing pack-years of smoking between menarche and first full-term
      pregnancy (FFTP). Studies with comprehensive quantitative life-time measures of
      passive smoking suggest an association between passive smoking dose and breast
      cancer risk. We conducted a study within the European Prospective Investigation
      into Cancer and Nutrition to examine the association between passive and active
      smoking and risk of invasive breast cancer and possible effect modification by
      known breast cancer risk factors. Among the 322,988 women eligible for the study,
      9,822 developed breast cancer (183,608 women with passive smoking information
      including 6,264 cases). When compared to women who never smoked and were not
      being exposed to passive smoking at home or work at the time of study
      registration, current, former and currently exposed passive smokers were at
      increased risk of breast cancer (hazard ratios (HR) [95% confidence interval
      (CI)] 1.16 [1.05-1.28], 1.14 [1.04-1.25] and 1.10 [1.01-1.20], respectively).
      Analyses exploring associations in different periods of life showed the most
      important increase in risk with pack-years from menarche to FFTP (1.73 [1.29
      2.32] for every increase of 20 pack-years) while pack-years smoked after
      menopause were associated with a significant decrease in breast cancer risk (HR =
      0.53, 95% CI: 0.34-0.82 for every increase of 20 pack-years). Our results provide
      an important replication, in the largest cohort to date, that smoking (passively
      or actively) increases breast cancer risk and that smoking between menarche and
      FFTP is particularly deleterious. 

PMID- 24590453
TI  - The population impact of familial cancer, a major cause of cancer.
AB  - The population attributable fraction (PAF) defines the proportion of a disease
      that would be prevented if the exposure to a particular risk factor was avoided.
      Familial risk is a known risk factor for many cancers, but an unbiased estimation
      of the PAF for familial risk requires a large study population to include rare
      cancers. PAFs and their corresponding standardized incidence ratios (SIRs) were
      calculated for familial relative risk among first-degree relatives (FDRs) and
      second-degree relatives (SDRs) diagnosed with the same (concordant) invasive or
      in situ cancers. Calculations were based on the Swedish Family-Cancer Database
      considering 8,148,737 individuals. To assess environmental effects, PAFs were
      also calculated for concordant cancers among spouses. Almost all cancers showed a
      significant familial risk. The highest PAFs were found for the common cancers of
      the prostate (13.94%), breast (7.46%) and colorectum (6.78%) among the FDRs. In
      the FDRs, the overall PAF for any concordant cancer was 4.20%, but in the SDRs,
      it was only 0.34%. The overall PAFs for in situ cancers were 0.86% and 0.56% for
      the FDRs and SDRs, respectively. The overall independent familial PAF was 5.96%
      for the invasive and in situ cancers in the FDRs and SDRs. The cancers between
      spouses yielded an overall PAF of 0.14%. For esophageal cancer, the risk among
      spouses was higher than the familial risk. Our study shows that the overall
      familial PAF of 5.96%, although underestimated for sex-specific cancers, ranks as
      the third most common population burden after tobacco smoking and unhealthy diet.

PMID- 24590456
TI  - Development and evaluation of a nutritionally enhanced multigrain tortilla snack.
AB  - An increased consumption of healthy foods to reduce chronic diseases risks is
      needed. We developed and evaluated a multigrain snack as a nutritive alternative
      to the highly consumed corn tortilla chips. Corn, wheat, and chickpea grains were
      boiled in 1% calcium oxide solution, steeped, washed, and ground before being
      mixed with soy protein isolate and oat flour to prepare the multigrain masa.
      Multigrain tortillas were moulded, baked, dried, and fried. Proximate
      composition, dietary fiber, protein quality, sensorial, and textural properties
      were evaluated. A commercial tortilla chip was used as control. The multigrain
      snack contained 153% more protein, 53% more dietary fiber, and 43 % less fat than
      commercial tortilla chips. Its lysine and isoleucine contents helped to increase
      the corrected-net protein utilization by 10%, while digestibility increased from
      83.5 to 91.8% as compared to commercial tortilla chips. The mean breaking force
      was 6,082 g for the multigrain snack and 4,780 g for the commercial tortilla
      chips. The mean acceptability score for the multigrain snack was 12.1
      (unstructured line scale 0-15 cm), and 82% of the panelists rated the snack as
      acceptable. In conclusion, a nutritionally enhanced multigrain tortilla snack was
      developed which provides significantly more dietary fiber and protein and less
      fat than traditional commercial corn tortilla chips, but with comparable
      appearance and high acceptability.

PMID- 24590454
TI  - Fatty acids found in dairy, protein and unsaturated fatty acids are associated
      with risk of pancreatic cancer in a case-control study.
AB  - Although many studies have investigated meat and total fat in relation to
      pancreatic cancer risk, few have investigated dairy, fish and specific fatty
      acids (FAs). We evaluated the association between intake of meat, fish, dairy,
      specific FAs and related nutrients and pancreatic cancer. In our American-based
      Mayo Clinic case-control study 384 cases and 983 controls frequency matched on
      recruitment age, race, sex and residence area (Minnesota, Wisconsin or Iowa, USA)
      between 2004 and 2009. All subjects provided demographic information and
      completed 144-item food frequency questionnaire. Logistic regression-calculated
      odds ratios (ORs) and 95% confidence intervals (95% CIs) were adjusted for age,
      sex, cigarette smoking, body mass index and diabetes mellitus. Significant
      inverse association (trend p-value < 0.05) between pancreatic cancer and the
      groupings (highest vs. lowest consumption quintile OR [95% CI]) was as follows:
      meat replacement (0.67 [0.43-1.02]), total protein (0.58 [0.39-0.86]), vitamin
      B12 (0.67 [0.44, 1.01]), zinc (0.48 [0.32, 0.71]), phosphorus (0.62 [0.41,
      0.93]), vitamin E (0.51 [0.33, 0.78]), polyunsaturated FAs (0.64 [0.42, 0.98])
      and linoleic acid (FA 18:2) (0.62 [0.40-0.95]). Increased risk associations were
      observed for saturated FAs (1.48 [0.97-2.23]), butyric acid (FA 4:0) (1.77 [1.19
      2.64]), caproic acid (FA 6:0) (2.15 [1.42-3.27]), caprylic acid (FA 8:0) (1.87
      [1.27-2.76]) and capric acid (FA 10:0) (1.83 [1.23-2.74]). Our study suggests
      that eating a diet high in total protein and certain unsaturated FAs is
      associated with decreased risk of developing pancreatic cancer in a dose
      dependent manner, whereas fats found in dairy increase risk. 

PMID- 24590455
TI  - Systemic GLIPR1-DeltaTM protein as a novel therapeutic approach for prostate
      cancer.
AB  - GLIPR1 is a p53 target gene known to be downregulated in prostate cancer, and
      increased endogenous GLIPR1 expression has been associated with increased
      production of reactive oxygen species, increased apoptosis, decreased c-Myc
      protein levels and increased cell cycle arrest. Recently, we found that
      upregulation of GLIPR1 in prostate cancer cells increases mitotic catastrophe
      through interaction with heat shock cognate protein 70 (Hsc70) and downregulation
      of Aurora kinase A and TPX2. In this study, we evaluated the mechanisms of
      recombinant GLIPR1 protein (glioma pathogenesis-related protein 1-transmembrane
      domain deleted [GLIPR1-DeltaTM]) uptake by prostate cancer cells and the efficacy
      of systemic GLIPR1-DeltaTM administration in a prostate cancer xenograft mouse
      model. GLIPR1-DeltaTM was selectively internalized by prostate cancer cells,
      leading to increased apoptosis through reactive oxygen species production and to
      decreased c-Myc protein levels. Interestingly, GLIPR1-DeltaTM was internalized
      through clathrin-mediated endocytosis in association with Hsc70. Systemic
      administration of GLIPR1-DeltaTM significantly inhibited VCaP xenograft growth.
      GLIPR1-DeltaTM showed no evidence of toxicity following elimination from mouse
      models 8 hr after injection. Our results demonstrate that GLIPR1-DeltaTM is
      selectively endocytosed by prostate cancer cells, leading to increased reactive
      oxygen species production and apoptosis, and that systemic GLIPR1-DeltaTM
      significantly inhibits growth of VCaP xenografts without substantial toxicity. 

PMID- 24590457
TI  - Differential hypoxic tolerance is mediated by activation of heat shock response
      and nitric oxide pathway.
AB  - The fall in ambient oxygen pressure in high-altitude milieu elicits a wide range
      of physiological responses in the myocardium, which may differ from individual to
      individual. This condition, known as hypobaric hypoxia, invokes the
      cardioprotective heat shock response. The present study focuses on the role
      played by this ubiquitous response in mediating a differential tolerance to acute
      hypoxic stress. Sprague Dawley rats were exposed to simulated hypoxia equivalent
      to 223 mmHg pressure, screened on the basis of time taken for onset of a
      characteristic hyperventilatory response, and categorized as susceptible (<10
      min), normal (10-25 min), or tolerant (>25 min). The tolerant animals displayed a
      significant upregulation of heat shock protein (Hsp)70/HSPA, evident through
      immunohistochemical staining of the cardiac tissue. The increased expression of
      transcription factor heat shock factor-1 led to the downstream activation of
      other chaperones, including Hsp90/HSPC, Hsp60/HSPD1, and Hsp27/HSPB1. The higher
      induction of HSPs in tolerant animals contributed to higher nitric oxide
      synthesis mediated by both endothelial nitric oxide synthase and inducible nitric
      oxide synthase activation. Conversely, susceptible animals showed significantly
      higher expression of the proinflammatory markers tumor necrosis factor alpha and
      nuclear factor kappa-light-chain enhancer of activated B cells in the myocardium.
      Evaluation of circulatory stress markers identified increased levels of reactive
      oxygen species, corticosterone and endothelin-1 in the susceptible animals
      highlighting their vulnerability to hypoxic stress. The heat shock response,
      through the action of chaperones and enhanced NO generation thus contributes
      substantially to the ability to sustain survival under acute sub lethal hypoxia.

PMID- 24590459
TI  - Metalophilic interaction in gold halide: quantum chemical study of AuX (X = F
      At).
AB  - Quantum chemical calculations of the structures, stabilities, and metalophilic
      interactions of AuX halides (X = F-At) at the CCSD(T) theoretical level with
      extended basis sets were performed. Natural bond orbital analysis showed that the
      present gold-halide metalophilic interactions mainly resulted from the overlap of
      an sp hybrid on halogen and a 6s6p5d hybrid on the Au atom. Analysis of electron
      density deformation showed a pronounced charge accumulation in the middle of the
      region between heavier X and Au, and clearly suggested the formation of covalent
      bond. Topological analysis of the Laplacian and total electronic energy densities
      at bond critical points showed the "intermediate type" character of gold-halide
      metalophilic interactions. Electron localization function showed the increased
      covalency from X = F to X = At.

PMID- 24590458
TI  - The involvement of mRNA processing factors TIA-1, TIAR, and PABP-1 during
      mammalian hibernation.
AB  - Mammalian hibernators survive low body temperatures, ischemia-reperfusion, and
      restricted nutritional resources via global reductions in energy-expensive
      cellular processes and selective increases in stress pathways. Consequently,
      studies that analyze hibernation uncover mechanisms which balance metabolism and
      support survival by enhancing stress tolerance. We hypothesized processing
      factors that influence messenger ribonucleic acid (mRNA) maturation and
      translation may play significant roles in hibernation. We characterized the amino
      acid sequences of three RNA processing proteins (T cell intracellular antigen 1
      (TIA-1), TIA1-related (TIAR), and poly(A)-binding proteins (PABP-1)) from
      thirteen-lined ground squirrels (Ictidomys tridecemlineatus), which all displayed
      a high degree of sequence identity with other mammals. Alternate Tia-1 and TiaR
      gene variants were found in the liver with higher expression of isoform b versus
      a in both cases. The localization of RNA-binding proteins to subnuclear
      structures was assessed by immunohistochemistry and confirmed by subcellular
      fractionation; TIA-1 was identified as a major component of subnuclear structures
      with up to a sevenfold increase in relative protein levels in the nucleus during
      hibernation. By contrast, there was no significant difference in the relative
      protein levels of TIARa/TIARb in the nucleus, and a decrease was observed for
      TIAR isoforms in cytoplasmic fractions of torpid animals. Finally, we used
      solubility tests to analyze the formation of reversible aggregates that are
      associated with TIA-1/R function during stress; a shift towards the soluble
      fraction (TIA-1a, TIA-1b) was observed during hibernation suggesting enhanced
      protein aggregation was not present during torpor. The present study identifies
      novel posttranscriptional regulatory mechanisms that may play a role in reducing
      translational rates and/or mRNA processing under unfavorable environmental
      conditions. 

PMID- 24590464
TI  - Preliminary examination of glucagon-like peptide-1 levels in women with purging
      disorder and bulimia nervosa.
AB  - OBJECTIVE: This study examined pre- and postprandial glucagon-like peptide 1 (GLP
      1) levels in women with bulimia nervosa (BN), purging disorder (PD), and non
      eating disorder control women to better understand whether alterations in
      satiation-related hormones in BN may be linked to binge-eating episodes or other
      altered ingestive behaviors. METHOD: Participants included women with BN (n =
      19), PD (n = 14), or controls (n = 14). Participants provided subjective ratings
      for hunger and fullness and plasma samples before and after consumption of a
      standardized test meal. RESULTS: As expected, GLP-1 levels increased
      significantly following test meal consumption; however, participants with BN
      displayed significantly lower GLP-1 levels compared to PD and control
      participants both before and after consumption of the test meal. There were no
      significant differences between PD and control participants in GLP-1 levels, but
      individuals with PD displayed significantly higher levels of fullness throughout
      the test meal as compared to both control and BN participants. DISCUSSION: Our
      findings provide preliminary evidence that reduced GLP-1 levels in individuals
      with BN may be associated with binge-eating episodes. Additionally, increased
      fullness in individuals with PD does not appear to be accounted for by
      exaggerated postprandial GLP-1 release.

PMID- 24590466
TI  - Validation of a generic approach to muscle water T2 determination at 3T in fat
      infiltrated skeletal muscle.
AB  - PURPOSE: To introduce a novel method for skeletal muscle water T2 determination
      in fat-infiltrated tissues, using a tri-exponential fit of the global muscle
      signal decay. MATERIALS AND METHODS: In all, 48 patients with various
      neuromuscular diseases were retrospectively selected and their thigh muscles
      analyzed. Each patient was imaged using a multispin-echo (MSME) sequence with a
      17-echo train. The transmit field (B1+) inhomogeneities were evaluated using the
      actual flip angle imaging method toward voxel sorting. Muscle water T2 was
      quantified using a tri-exponential signal decay model. The difference between
      water T2 of voxels within the same muscle but having different fat ratio was
      analyzed using nonparametric statistical tests. In addition, we evaluated the
      correlation between fat ratio and T2 values obtained using both a mono- and tri
      exponential approach. RESULTS: The results showed that muscle water T2 values
      obtained using a tri-exponential approach combined with B1+ map-based voxel
      sorting were independent of the fat infiltration degree inside the muscle (R(2) <
      0.03). This was not the case using the mono-exponential model, which measured
      different T2s between voxels of the same muscle but with various fat ratio (R(2)
      > 0.67; P < 10e(-4) ). CONCLUSION: The tri-exponential model is an accurate tool
      to monitor muscle tissue disease activity devoid of bias introduced by fat
      infiltration.

PMID- 24590467
TI  - Why is the sunny side always up? Explaining the spatial mapping of concepts by
      language use.
AB  - Humans appear to rely on spatial mappings to represent and describe concepts. The
      conceptual cuing effect describes the tendency for participants to orient
      attention to a spatial location following the presentation of an unrelated cue
      word (e.g., orienting attention upward after reading the word sky). To date, such
      effects have predominately been explained within the embodied cognition
      framework, according to which people's attention is oriented on the basis of
      prior experience (e.g., sky -> up via perceptual simulation). However, this does
      not provide a compelling explanation for how abstract words have the same ability
      to orient attention. Why, for example, does dream also orient attention upward?
      We report on an experiment that investigated the role of language use
      (specifically, collocation between concept words and spatial words for up and
      down dimensions) and found that it predicted the cuing effect. The results
      suggest that language usage patterns may be instrumental in explaining conceptual
      cuing. 

PMID- 24590468
TI  - Repetition priming in picture naming: sustained learning through the speeding of
      multiple processes.
AB  - Picture naming has been used by vision researchers to study object
      identification, by language researchers to study word production, and by memory
      researchers to study implicit memory. Response times for naming repeated pictures
      decrease with successive repetitions. Repetition priming in picture naming
      involves an implicit, nonhippocampal form of memory. In this review, the
      processes speeded with repetition are decomposed, the time course of the effect
      is characterized, the factors affecting the magnitude of priming are enumerated,
      and possible mechanisms of priming are evaluated. Both behavioral response time
      and neuroimaging studies are considered. The processes that are speeded with
      repetition include high-level object identification and word production
      processes, but not low-level visual processes or articulation. Repetition priming
      lasts for at least several weeks and follows a typical forgetting function. The
      mechanism of priming is concluded to be speeded completion of the component
      processes of picture naming. 

PMID- 24590469
TI  - A training and development project to improve services and opportunities for
      social inclusion for children and young people with autism in Romania.
AB  - In 2010, the Romanian Angel Appeal Foundation launched a 3-year national training
      and development programme to develop and deliver a model of diagnostic and
      therapeutic services aimed at promoting social inclusion for children and young
      people with autism spectrum disorders. The project adopted a number of strategies
      aimed at developing knowledge and skills among professionals and increasing
      awareness in political and public spheres: (a) a three-stage training programme
      designed to increase knowledge of autism spectrum disorders and promote best
      practice among professionals working in services providing for children with
      autism spectrum disorders and their families, on a nationwide basis; (b) two
      online courses for general practitioners and psychiatrists, with content relating
      to the identification, diagnosis and treatment of autism spectrum disorders; (c)
      a total of 40 counselling and assistance centres for people with autism spectrum
      disorders were launched in partnership with local authorities; (d) a national
      strategy for social and professional integration of people with autism spectrum
      disorders developed through consultation with political, statutory and voluntary
      sector partners; and (e) a nationwide media campaign to raise awareness of the
      needs of children and young people with autism spectrum disorders that reached
      over eight million people. The project provides a transferable model to achieve
      important improvements in the quantity and quality of services on a national
      level within a brief time frame. 

PMID- 24590470
TI  - Osteosarcoma cells enhance angiogenesis visualized by color-coded imaging in the
      in vivo Gelfoam(r) assay.
AB  - We previously described a color-coded imaging model that can quantify the length
      of nascent blood vessels using Gelfoam(r) implanted in nestin-driven green
      fluorescent protein (ND-GFP) nude mice. In ND-GFP mice, nascent blood vessels are
      labeled with GFP. We report here that osteosarcoma cells promote angiogenesis in
      the Gelfoam(r) angiogenesis assay in ND-GFP mice. Gelfoam(r) was initially
      transplanted subcutaneously in the flank of transgenic ND-GFP nude mice. Seven
      days after transplantation of Gelfoam(r), skin flaps were made and human 143B
      osteosarcoma cells expressing green fluorescent protein (GFP) in the nucleus and
      red fluorescent protein (RFP) in cytoplasm were injected into the transplanted
      Gelfoam(r). The control-group mice had only implanted Gelfoam(r). Skin flaps were
      made at days 14, 21, and 28 after transplantation of the Gelfoam(r) to allow
      imaging of vascularization in the Gelfoam(r) using a variable-magnification small
      animal imaging system and confocal fluorescence microscopy. ND-GFP expressing
      nascent blood vessels penetrated and spread into the Gelfoam(r) in a time
      dependent manner in both control and osteosarcoma-implanted mice. ND-GFP
      expressing blood vessels in the Gelfoam(r) of the osteosarcoma-implanted mice
      were associated with the cancer cells and larger and longer than in the
      Gelfoam(r)-only implanted mice (P < 0.01). The results presented in this report
      demonstrate strong angiogenesis induction by osteosarcoma cells and suggest this
      process is a potential therapeutic target for this disease.

PMID- 24590471
TI  - Minimally invasive implantation of biventricular assist devices.
AB  - As minimally invasive left ventricular assist device implantation is being
      advocated and more widely performed, bailout strategies for postoperative right
      ventricular failure (RVF) become necessary. We describe our surgical technique
      for additional right ventricular assist device implantation through a third mini
      thoracotomy incision. This new technique allows avoidance of sternotomy even if
      RVF occurs. 

PMID- 24590472
TI  - Hughes-Stovin syndrome: a rare and often overlooked cause of hemoptysis and
      pulmonary artery aneurysms.

PMID- 24590473
TI  - Learning thoracoscopic lobectomy in resident training.
AB  - BACKGROUND: Thoracoscopic lobectomy is a safe and effective procedure; however,
      the ways by which to incorporate this technically demanding procedure into
      residency training is still unknown. We reported on the outcomes of thoracoscopic
      lobectomies performed by a single thoracic resident, who was simultaneously
      undergoing training for both open and thoracoscopic lobectomies. PATIENTS AND
      METHODS: Between January 2010, and May 2011, data from 87 consecutive
      thoracoscopic lobectomies that were performed by a trainee surgeon (B.-Y.W.) were
      prospectively obtained. Data were grouped into the first 30 and subsequent 57
      cases. Patient characteristics, operative data, complications, and surgical
      pathology were analyzed. RESULTS: The mean operating time in group 2 was
      significantly lower compared with group 1 (264.0 +/- 45.9 min in group 1 vs.
      197.5 +/- 57.7 min in group 2; p<0.001). There were no mortalities in both the
      groups and no significant differences in postoperative complications.
      CONCLUSIONS: Thoracoscopic lobectomy can be taught to a nonexperienced thoracic
      resident during an open procedure without compromising the safety of patients. It
      appears that surgical performance reaches a plateau after the completion of 30
      cases.

PMID- 24590474
TI  - Results of surgical treatment for non-small cell lung cancer with positive sputum
      cytology: experience from a single institution.
AB  - BACKGROUND: Little is known about the prognostic value of positive sputum
      cytology in patients with non-small cell lung cancer (NSCLC). PATIENTS AND
      METHODS: We retrospectively examined the clinicopathological data of 30 patients
      who had undergone complete resection for NSCLC with positive sputum cytology
      between September 2002 and June 2011. RESULTS: Distant recurrence occurred
      significantly more frequently in the patients with adenocarcinoma (Ad) than in
      those with squamous cell carcinoma (p = 0.01). The most frequent metastatic site
      after surgery was the brain, occurring in five patients with Ad. The 5-year
      disease-free survival (DFS) and overall survival (OS) rates of the 30 patients
      were 53 and 49%, respectively. In multivariate analyses, radiographic feature of
      pneumonic-type shadow and pathological N (pN) 1-2 status were the independent
      factors significantly correlated with poor DFS (p = 0.009, 0.001, respectively),
      whereas pN 1-2 status was the only independent factor significantly correlated
      with poor OS (p = 0.009). CONCLUSION: Surgical outcome for NSCLC with positive
      sputum cytology was unfavorable at our institution. Close surveillance after a
      curative resection is mandatory for those patients presenting with radiographic
      feature of pneumonic-type shadow as those with lymph node metastases because they
      are at high risk for recurrence.

PMID- 24590475
TI  - Alteration of the murine gastrointestinal microbiota by tigecycline leads to
      increased susceptibility to Clostridium difficile infection.
AB  - Antibiotics can play dual roles in Clostridium difficile infection (CDI);
      antibiotic treatment increases the risk of CDI, and antibiotics are used to treat
      CDI. The glycylcycline antibiotic tigecycline has broad antimicrobial activity,
      yet it is rarely associated with the development of CDI, presumably due to its
      activity against C. difficile. In this study, we investigated how tigecycline
      treatment affects the structure of the gut microbiota and susceptibility to CDI
      by treating mice with tigecycline (n = 20) or saline (n = 8) for 10 days. A
      sequence analysis of the bacterial 16S rRNA gene amplicons was used to monitor
      changes in the fecal microbiota. A subset of the mice was followed for 5 weeks
      after the end of treatment. The remaining mice were challenged with C. difficile
      strain VPI 10463 spores 2 days after the tigecycline treatment ended. Tigecycline
      treatment resulted in major shifts in the gut microbiota, including large
      decreases in Bacteroidetes levels and large increases in Proteobacteria levels.
      Mice with tigecycline-altered microbial communities were susceptible to challenge
      with C. difficile spores and developed clinical signs of severe CDI. Five weeks
      after the cessation of tigecycline treatment, the recovery of the bacterial
      community was incomplete and diversity was lower than in the untreated controls.
      Antibiotics with intrinsic activity against C. difficile can still alter the
      microbiota in a way that leads to susceptibility to CDI after discontinuation of
      the drug. These results indicate that microbiotic dynamics are key in the
      development of CDI, and a better understanding of these dynamics may lead to
      better strategies to prevent and treat this disease. 

PMID- 24590477
TI  - Effectiveness of primary anti-Aspergillus prophylaxis during remission induction
      chemotherapy of acute myeloid leukemia.
AB  - Although antifungal prophylaxis is frequently administered to patients with acute
      myeloid leukemia (AML) during remission-induction chemotherapy (RIC), its impact
      on reducing invasive fungal infections (IFIs) outside clinical trials is rarely
      reported. We performed a retrospective observational study to identify risk
      factors for development of IFIs (definite or probable, using revised European
      Organization for Research and Treatment of Cancer [EORTC] criteria) and all-cause
      mortality in a cohort of 152 AML patients receiving RIC (2009 to 2011). We also
      compared rates of IFI and mortality in patients who received echinocandin versus
      anti-Aspergillus azole (voriconazole or posaconazole) prophylaxis during the
      first 120 days of RIC. In multivariate analysis, clofarabine-based RIC (hazard
      ratio [HR], 3.5; 95% confidence interval [CI], 1.5 to 8.3; P = 0.004) and
      echinocandin prophylaxis (HR, 4.6; 95% CI, 1.8 to 11.9; P = 0.002) were
      independently associated with higher rates of IFI rates during RIC. Subsequent
      analysis failed to identify any malignancy- or chemotherapy-related covariates
      linked to echinocandin prophylaxis that accounted for the higher rates of
      breakthrough IFI. Although the possibility of other confounding variables cannot
      be excluded, our findings suggest that echinocandin-based prophylaxis during RIC
      for AML may be associated with a higher risk of breakthrough IFI. 

PMID- 24590476
TI  - In vitro and in vivo studies of the biological activity of novel arylimidamides
      against Trypanosoma cruzi.
AB  - Fifteen novel arylimidamides (AIAs) (6 bis-amidino and 9 mono-amidino analogues)
      were assayed against Trypanosoma cruzi in vitro and in vivo. All the bis-AIAs
      were more effective than the mono-AIAs, and two analogues, DB1967 and DB1989,
      were further evaluated in vivo. Although both of them reduced parasitemia,
      protection against mortality was not achieved. Our results show that the number
      of amidino-terminal units affects the efficacy of arylimidamides against T.
      cruzi. 

PMID- 24590478
TI  - Tranylcypromine reduces herpes simplex virus 1 infection in mice.
AB  - Herpes simplex virus 1 (HSV-1) infects the majority of the human population and
      establishes latency by maintaining viral genomes in neurons of sensory ganglia.
      Latent virus can undergo reactivation to cause recurrent infection. Both primary
      and recurrent infections can cause devastating diseases, including encephalitis
      and corneal blindness. Acyclovir is used to treat patients, but virus resistance
      to acyclovir is frequently reported. Recent in vitro findings reveal that
      pretreatment of cells with tranylcypromine (TCP), a drug widely used in the
      clinic to treat neurological disorders, restrains HSV-1 gene transcription by
      inhibiting the histone-modifying enzyme lysine-specific demethylase 1. The
      present study was designed to examine the anti-HSV-1 efficacy of TCP in vivo
      because of the paucity of reports on this issue. Using the murine model, we found
      that TCP decreased the severity of wild-type-virus-induced encephalitis and
      corneal blindness, infection with the acyclovir-resistant (thymidine kinase
      negative) HSV-1 mutant, and tissue viral loads. Additionally, TCP blocked in vivo
      viral reactivation in trigeminal ganglia. These results support the therapeutic
      potential of TCP for controlling HSV-1 infection. 

PMID- 24590479
TI  - Efficacy of the novel topical antimicrobial agent PXL150 in a mouse model of
      surgical site infections.
AB  - Antimicrobial peptides have recently emerged as a promising new group to be
      evaluated in the therapeutic intervention of infectious diseases. This study
      evaluated the anti-infectious effect of the short, synthetic, broad-spectrum
      antimicrobial peptide PXL150 in a mouse model of staphylococcal surgical site
      infections. We found that administration of PXL150, formulated in an aqueous
      solution or in a hydroxypropyl cellulose gel, significantly reduced the bacterial
      counts in the wound compared with placebo treatment, warranting further
      investigations of the potential of this peptide as a novel local treatment of
      microbial infections. 

PMID- 24590480
TI  - OXA-253, a variant of the carbapenem-hydrolyzing class D beta-lactamase OXA-143
      in Acinetobacter baumannii.
AB  - The carbapenem-hydrolyzing class D beta-lactamase OXA-253 was identified in an
      Acinetobacter baumannii clinical isolate belonging to sequence type 113 (ST113)
      in Brazil. OXA-253 shares 93.8% amino acid identity with OXA-143. The blaOXA-253
      gene is located on a ca. 20-kb plasmid. The genetic environment of the blaOXA-253
      gene shares the highest identity with ubiquitous GR2 group plasmids usually
      carrying blaOXA-24/-40 genes. 

PMID- 24590481
TI  - Cross-resistance between clofazimine and bedaquiline through upregulation of
      MmpL5 in Mycobacterium tuberculosis.
AB  - The antileprosy drug clofazimine is also of interest for the treatment of
      multidrug-resistant tuberculosis. To understand possible resistance mechanisms,
      clofazimine-resistant Mycobacterium tuberculosis mutants were isolated in vitro,
      and, unexpectedly, found to be cross-resistant to bedaquiline. Mutations in the
      transcriptional regulator Rv0678, with concomitant upregulation of the
      multisubstrate efflux pump, MmpL5, accounted for this cross-resistance. Mutation
      in Rv0678 should therefore be considered a confounding factor for the treatment
      of tuberculosis with clofazimine or bedaquiline. 

PMID- 24590482
TI  - Antimicrobial treatment improves mycobacterial survival in nonpermissive growth
      conditions.
AB  - Antimicrobials targeting cell wall biosynthesis are generally considered inactive
      against nonreplicating bacteria. Paradoxically, we found that under nonpermissive
      growth conditions, exposure of Mycobacterium bovis BCG bacilli to such
      antimicrobials enhanced their survival. We identified a transcriptional
      regulator, RaaS (for regulator of antimicrobial-assisted survival), encoded by
      bcg1279 (rv1219c) as being responsible for the observed phenomenon. Induction of
      this transcriptional regulator resulted in reduced expression of specific ATP
      dependent efflux pumps and promoted long-term survival of mycobacteria, while its
      deletion accelerated bacterial death under nonpermissive growth conditions in
      vitro and during macrophage or mouse infection. These findings have implications
      for the design of antimicrobial drug combination therapies for persistent
      infectious diseases, such as tuberculosis. 

PMID- 24590483
TI  - Antibacterial activity of pepducins, allosterical modulators of formyl peptide
      receptor signaling.
AB  - Pepducins containing a fatty acid linked to an amino acid sequence derived from
      cytosolic parts of a G-protein-coupled receptor (GPCR) constitute a new group of
      lipopeptide tools in GPCR studies. Pepducins corresponding to the third
      intracellular loop of formyl peptide receptor 2 (FPR2) activate human
      neutrophils, and we show here that, in addition, these allosteric modulators of
      receptor activity also kill bacteria. The functional dualism of FPR2 pepducins
      could potentially be explored as a novel class of antibacterial drugs with
      immunomodulatory properties. 

PMID- 24590484
TI  - Hepatitis C virus genetic variability and the presence of NS5B resistance
      associated mutations as natural polymorphisms in selected genotypes could affect
      the response to NS5B inhibitors.
AB  - Because of the extreme genetic variability of hepatitis C virus (HCV), we
      analyzed the NS5B polymerase genetic variability in circulating HCV
      genotypes/subtypes and its impact on the genetic barrier for the development of
      resistance to clinically relevant nucleoside inhibitors (NIs)/nonnucleoside
      inhibitors (NNIs). The study included 1,145 NS5B polymerase sequences retrieved
      from the Los Alamos HCV database and GenBank. The genetic barrier was calculated
      for drug resistance emergence. Prevalence and genetic barrier were calculated for
      1 major NI and 32 NNI resistance variants (13 major and 19 minor) at 21 total
      NS5B positions. Docking calculations were used to analyze sofosbuvir affinity
      toward the diverse HCV genotypes. Overall, NS5B polymerase was moderately
      conserved among all HCV genotypes, with 313/591 amino acid residues (53.0%)
      showing <=1% variability and 83/591 residues (14.0%) showing high variability
      (>=25.1%). Nine NNI resistance variants (2 major variants, 414L and 423I; 7 minor
      variants, 316N, 421V, 445F, 482L, 494A, 499A, and 556G) were found as natural
      polymorphisms in selected genotypes. In particular, 414L and 423I were found in
      HCV genotype 4 (HCV-4) (n = 14/38, 36.8%) and in all HCV-5 sequences (n = 17,
      100%), respectively. Regardless of HCV genotype, the 282T major NI resistance
      variant and 10 major NNI resistance variants (316Y, 414L, 423I/T/V, 448H, 486V,
      495L, 554D, and 559G) always required a single nucleotide substitution to be
      generated. Conversely, the other 3 major NNI resistance variants (414T, 419S, and
      422K) were associated with a different genetic barrier score development among
      the six HCV genotypes. Sofosbuvir docking analysis highlighted a better ligand
      affinity toward HCV-2 than toward HCV-3, in agreement with the experimental
      observations. The genetic variability among HCV genotypes, particularly with the
      presence of polymorphisms at NNI resistance positions, could affect their
      responsiveness to NS5B inhibitors. A pretherapy HCV NS5B sequencing could help to
      provide patients with the full efficacy of NNI-containing regimens. 

PMID- 24590485
TI  - Mechanism of Escherichia coli resistance to Pyrrhocoricin.
AB  - Due to their lack of toxicity to mammalian cells and good serum stability,
      proline-rich antimicrobial peptides (PR-AMPs) have been proposed as promising
      candidates for the treatment of infections caused by antimicrobial-resistant
      bacterial pathogens. It has been hypothesized that these peptides act on multiple
      targets within bacterial cells, and therefore the likelihood of the emergence of
      resistance was considered to be low. Here, we show that spontaneous Escherichia
      coli mutants resistant to pyrrhocoricin arise at a frequency of approximately 6 *
      10(-7). Multiple independently derived mutants all contained a deletion in a
      nonessential gene that encodes the putative peptide uptake permease SbmA.
      Sensitivity could be restored to the mutants by complementation with an intact
      copy of the sbmA gene. These findings question the viability of the development
      of insect PR-AMPs as antimicrobials. 

PMID- 24590486
TI  - Trends and seasonal variation in outpatient antibiotic prescription rates in the
      United States, 2006 to 2010.
AB  - Antibiotic-resistant bacteria are an increasing threat to the effectiveness of
      antibiotics. The majority of antibiotics are prescribed in primary care settings
      for upper respiratory tract infections. The purpose of this study was to describe
      seasonal trends in outpatient antibiotic prescriptions (Rx) in the United States
      over a 5-year period. This study was a retrospective, cross-sectional observation
      of systemic antibiotic prescriptions in the outpatient setting from 2006 to 2010.
      Winter months were defined as the first and fourth quarters of the calendar year.
      Antibiotic prescribing rates were calculated (prescriptions/1,000 population)
      using annual U.S. Census Bureau population data. Over 1.34 billion antibiotic
      prescriptions were dispensed over the 5-year period. The antibiotic prescription
      (Rx) rate decreased from 892 Rx/1,000 population in 2006 to 867 Rx/1,000
      population in 2010. Penicillins and macrolides were the primary antibiotic
      classes prescribed, but penicillin prescribing decreased while macrolide
      prescribing increased over the study period. Overall, antibiotic prescriptions
      were 24.5% higher in winter months than in the summer, with the largest
      difference (28.8%) in 2008 and the smallest (20.4%) in 2010. This seasonality was
      consistently drug class dependent, driven by 75% and 100% increases in penicillin
      and macrolide prescriptions, respectively, in the winter months. The mean
      outpatient antibiotic prescription rate decreased in the United States from 2006
      to 2010. More antibiotic prescribing, predominately driven by the macrolide and
      penicillin classes, in the outpatient setting was observed in the winter months.
      Understanding annual variability in antibiotic use can assist with designing
      interventions to improve the judicious use of antibiotics. 

PMID- 24590487
TI  - Supercritical carbon dioxide assisted deposition of Fe(3)O(4) nanoparticles on
      hierarchical porous carbon and their lithium-storage performance.
AB  - A composite of highly dispersed Fe3 O4 nanoparticles (NPs) anchored in three
      dimensional hierarchical porous carbon networks (Fe3 O4 /3DHPC) as an anode
      material for lithium-ion batteries (LIBs) was prepared by means of a deposition
      technique assisted by a supercritical carbon dioxide (scCO2 )-expanded ethanol
      solution. The as-synthesized Fe3 O4 /3DHPC composite exhibits a bimodal porous 3D
      architecture with mutually connected 3.7 nm mesopores defined in the macroporous
      wall on which a layer of small and uniform Fe3 O4 NPs was closely coated. As an
      anode material for LIBs, the Fe3 O4 /3DHPC composite with 79 wt % Fe3 O4 (Fe3 O4
      /3DHPC-79) delivered a high reversible capacity of 1462 mA h g(-1) after 100
      cycles at a current density of 100 mA g(-1) , and maintained good high-rate
      performance (728, 507, and 239 mA h g(-1) at 1, 2, and 5 C, respectively).
      Moreover, it showed excellent long-term cycling performance at high current
      densities, 1 and 2 A g(-1) . The enhanced lithium-storage behavior can be
      attributed to the synergistic effect of the porous support and the homogeneous
      Fe3 O4 NPs. More importantly, this straightforward, highly efficient, and green
      synthetic route will definitely enrich the methodologies for the fabrication of
      carbon-based transition-metal oxide composites, and provide great potential
      materials for additional applications in supercapacitors, sensors, and catalyses.

PMID- 24590488
TI  - Identification of polyamine transporters in plants: paraquat transport provides
      crucial clues.
AB  - Polyamine (PA) transport as well as PA biosynthesis, degradation and conjugation
      plays a vital role in the regulation of intracellular PA levels, which are
      essential for cell growth. Generally, PA uptake activity is elevated in rapidly
      proliferating cells. Previous studies showed that PA uptake in plant cells
      occurred via energy-dependent, protein-mediated transport systems. Numerous lines
      of evidence suggest that paraquat (PQ), one of the most widely used herbicides,
      is transported by the PA transport system in diverse organisms including plants.
      The PA/PQ transport interactions are proposed to be due to specific structural
      similarities between PA and PQ. The understanding of PA transport mechanisms has
      progressed in parallel with that of PQ transport, but the molecular identity of
      the plant PA/PQ transporter has remained an enigma. Recently, independent studies
      identified the L-type amino acid transporter (LAT) family transmembrane proteins
      as transporters of both PA and PQ. Arabidopsis LAT family proteins showed
      different subcellular localization properties, which suggested that these
      transporters were involved in intracellular PA trafficking and PA uptake across
      the plasma membrane. The identification of plant PA transporters is an important
      step in understanding the mechanism of PA homeostasis in plant cells. In this
      review, we highlight recent advances in the study of PA transport systems that
      are linked to the understanding of PQ translocation.

PMID- 24590489
TI  - In situ altering of the extracellular matrix to direct the programming of
      endogenous stem cells.

PMID- 24590490
TI  - Consistent biomechanical phenotyping of common carotid arteries from seven
      genetic, pharmacological, and surgical mouse models.
AB  - The continuing lack of longitudinal histopathological and biomechanical data for
      human arteries in health and disease highlights the importance of studying the
      many genetic, pharmacological, and surgical models that are available in mice. As
      a result, there has been a significant increase in the number of reports on the
      biomechanics of murine arteries over the past decade, particularly for the common
      carotid artery. Whereas most of these studies have focused on wild-type controls
      or comparing controls vs. a single model of altered hemodynamics or vascular
      disease, there is a pressing need to compare results across many different models
      to understand more broadly the effects of genetic mutations, pharmacological
      treatments, or surgical alterations on the evolving hemodynamics and the
      microstructure and biomechanical properties of these vessels. This paper
      represents a first step toward this goal, that is, a biomechanical phenotyping of
      common carotid arteries from control mice and seven different mouse models that
      represent alterations in elastic fiber integrity, collagen remodeling, and smooth
      muscle cell functionality. 

PMID- 24590491
TI  - Cone-beam computed tomographic analysis of the morphological characterization of
      the nasopalatine canal in a pediatric population.
AB  - PURPOSE: Knowledge of the nasopalatine canal (NPC) is necessary for understanding
      the morphology and pathogenesis of lesions that occur in this region. The purpose
      of the present study was to analyze the dimensions and anatomic characteristics
      of the NPC in a pediatric population using cone-beam computed tomography (CBCT).
      STUDY DESIGN: Reformatted sagittal, coronal, and axial slices of 368 individual
      CBCT images were analyzed with regard to dimensions and anatomic features of the
      NPC. RESULTS: Funnel shape of the NPC was most commonly found [26.9 % (99)],
      followed by banana shape [19.6 % (72)]. There was no statistically significant
      difference (p = 0.317) between girls and boys in terms of NPC shape. The mean
      width of incisive foramen was found to be 2.53 mm with a significant difference
      (0.002). The mean NPC length was found to be 10.83 mm and the mean canal length
      was found to be significantly longer in boys than girls (p < 0.000). CONCLUSION:
      The present study provides new information on the literature concerning the
      identification of the anatomical structure of NPC. This finding may assist
      clinicians in understanding the morphology and preventing possible complications
      in this region.

PMID- 24590495
TI  - Direct alpha-siladifluoromethylation of lithium enolates with Ruppert-Prakash
      reagent via C-F bond activation.
AB  - The direct alpha-siladifluoromethylation of lithium enolates with the Ruppert
      Prakash reagent (CF3 TMS) is shown to construct the tertiary and quaternary
      carbon centers. The Ruppert-Prakash reagent, which is versatile for various
      trifluoromethylation as a trifluoromethyl anion (CF3 (-) ) equivalent, can be
      employed as a siladifluoromethyl cation (TMSCF2 (+) ) equivalent by C?F bond
      activation due to the strong interaction between lithium and fluorine atoms. 

PMID- 24590496
TI  - Unprecedented high-nuclear transition-metal-cluster-substituted
      heteropolyoxoniobates: synthesis by {V8 } ring insertion into the POM matrix and
      antitumor activities.
AB  - Reactions of hexaniobate with vanadate in the presence of Ni(2+) , Zn(2+) , or
      Cu(2+) have furnished three high-nuclear vanadium cluster-substituted
      heteropolyoxoniobates (HPNs): {Ni(en)3 }5 H{V(V) Nb8 V(IV) 8 O44 }?9 H2 O (1),
      (H2 en)Na2 [{Zn(en)2 (Hen)}{Zn(en)2 (H2 O)}2 {PNb8 V(IV) 8 O44 }]?11 H2 O (2),
      and Na{Cu(en)2 }3 {[Cu(en)2 ]2 [PNb8 V(IV) 8 O44 ]}?11 H2 O (3) (en=1,2
      diaminoethane). Their structures have been determined and characterized by single
      crystal X-ray diffraction analysis, thermogravimetric analysis (TGA), and
      elemental analysis. Structural analysis has revealed that compounds 1-3 contain
      similar {V8 }-substituted [X(V) Nb8 V(IV) 8 O44 ](11-) (X=P, V) clusters,
      obtained by inserting a {V8 } ring into tetravacant HPN [XNb8 O36 ](27-) . To the
      best of our knowledge, compounds 1-3 represent the first high-nuclear vanadium
      cluster-substituted HPNs, and compound 1 is the largest vanadoniobate cluster yet
      obtained in HPN chemistry. Nickel and zinc cations have been introduced into HPNs
      for the first time, which might promise a more diverse set of structures in this
      family. Antitumor studies have indicated that compounds 1 and 2 exhibit high
      activity against human gastric cancer SGC-7901 cells, SC-1680 cells, and MG-63
      cells. 

PMID- 24590498
TI  - New mechanistic insight into stepwise metal-center exchange in a metal-organic
      framework based on asymmetric Zn(4) clusters.
AB  - Herein, a mechanism of stepwise metal-center exchange for a specific metal
      organic framework, namely, [Zn4 (dcpp)2 (DMF)3 (H2 O)2 ]n (H4 dcpp=4,5-bis(4'
      carboxylphenyl)phthalic acid), is disclosed for the first time. The coordination
      stabilities between the central metal atoms and the ligands as well as the
      coordination geometry are considered to be dominant factors in this stepwise
      exchange mechanism. A new magnetic analytical method and a theoretical model
      confirmed that the exchange mechanism is reasonable. When the metathesis reaction
      occurs between Cu(II) ions and framework Zn(II) ions, the magnetic exchange
      interaction of each pair of Cu(II) centers gradually strengthens with increasing
      amount of framework Cu(II) ions. By analyzing the changes of coupling constants
      in the Cu-exchanged products, it was deduced that Zn4 and Zn3 are initially
      replaced, and then Zn1 and Zn2 are replaced later. The theoretical calculation
      further verified that Zn4 is replaced first, Zn3 next, then Zn1 and Zn2 last, and
      the coordination stability dominates the Cu/Zn exchange process. For the Ni/Zn
      and Co/Zn exchange processes, besides the coordination stability, the preferred
      coordination geometry was also considered in the stepwise-exchange behavior. As
      Ni(II) and Co(II) ions especially favor octahedral coordination geometry in
      oxygen-ligand fields, Ni(II) ions and Co(II) ions could only selectively exchange
      with the octahedral Zn(II) ions, as was also confirmed by the experimental
      results. The stepwise metal-exchange process occurs in a single crystal-to-single
      crystal fashion. 

PMID- 24590497
TI  - Comprehensive evaluation of the physicochemical properties of Ln(III) complexes
      of aminoethyl-DO3A as pH-responsive T(1) -MRI contrast agents.
AB  - N-Substituted aminoethyl groups were attached to 1,4,7,10-tetraazacyclododecane
      1,4,7-triacetic acid (DO3A) with the aim to design pH-responsive Ln(III)
      complexes based on the pH-dependent on/off ligation of the amine nitrogen to the
      metal ion. The following ligands were synthesized: AE-DO3A (aminoethyl-DO3A), MAE
      DO3A (N-methylaminoethyl-DO3A), DMAE-DO3A (N,N-dimethylaminoethyl-DO3A) and MEM
      AE-DO3A (N-methoxyethyl-N-methylaminoethyl-DO3A). The physicochemical properties
      of the Ln(III) complexes were investigated for the evaluation of their potential
      applicability as magnetic resonance imaging (MRI) contrast agents. In particular,
      a (1) H and (17) O NMR relaxometric study was carried out for these Gd(III)
      complexes at two different pH values: at basic pH (pendant amino group
      coordinated to the metal centre) and at acidic pH (protonated amine, not
      interacting with the metal ion). Eu(III) complexes allow one to estimate the
      number of inner-sphere water molecules through luminescence lifetime measurements
      and obtain some structural information through variable-temperature (VT) high
      resolution (1) H NMR studies. Equilibria between differently hydrated species
      were found for most of the complexes at both acidic and basic pH. The
      thermodynamic stability of Ca(II) , Zn(II) , Cu(II) and Ln(III) complexes and
      kinetics of formation and dissociation reactions of Ln(III) complexes of AE-DO3A
      and DMAE-DO3A were investigated showing stabilities comparable to currently
      approved Gd(III) -based CAs. In detail, higher total basicity (Sigmalog Ki (H) )
      and higher stability constants of Ln(III) complexes were found for AE-DO3A with
      respect to DMAE-DO3A (i.e., log KGd-AE-DO3A =22.40 and log KGd-DMAE-DO3A =20.56).
      The transmetallation reactions of Gd(III) complexes are very slow (Gd-AE-DO3A:
      t1/2 =2.7*10(4)  h; Gd-DMAE-DO3A: 1.1*10(5)  h at pH 7.4 and 298 K) and occur
      through proton-assisted dissociation.

PMID- 24590499
TI  - Alcohol intake and risk of Parkinson's disease: a meta-analysis of observational
      studies.
AB  - BACKGROUND: The association of alcohol intake with risk of Parkinson's disease
      remains unclear. METHODS: Pertinent studies were identified in PubMed and EMBASE.
      The fixed-effect or random-effect model was selected based on heterogeneity. The
      dose-response relationship was assessed by restricted cubic splines. RESULTS: We
      included 32 articles, involving 677,550 subjects (9994 cases). The smoking
      adjusted risk of Parkinson's disease for the highest versus lowest level of
      alcohol intake was relative risk (RR) 0.78 (95% confidence interval [CI], 0.67
      0.92) overall, 0.86 (95% CI, 0.75-0.995) in prospective studies, and 0.74 (95%
      CI, 0.58-0.96) in matched case-control studies. A significant association was
      found with beer (0.59; 95% CI, 0.39-0.90) but not with wine and liquor, and for
      males (0.65; 95% CI, 0.47-0.90) after a sensitivity analysis but not for females.
      The risk of Parkinson's disease decreased by 5% (0.95; 95% CI, 0.89-1.02) for
      every 1 drink/day increment in alcohol intake in a linear (Pfor nonlinearity  =
      0.85) dose-response manner. CONCLUSIONS: Alcohol intake, especially beer, might
      be inversely associated with risk of Parkinson's disease

PMID- 24590501
TI  - A Bronsted acid catalyzed redox arylation.
AB  - A Bronsted acid catalyzed redox arylation of ynamides that employs aryl
      sulfoxides as the arylating agents is reported. This metal-free transformation
      proceeds at room temperature and efficiently affords alpha-arylated
      oxazolidinones in a redox-neutral, atom-economic fashion. 

PMID- 24590502
TI  - Advances in interventional cardiology: MitraClip.
AB  - Severe mitral valve regurgitation is a serious condition with significant
      morbidity and mortality. It is not uncommon recently, to see patients with
      significant mitral valve regurgitation that are considered "non-surgical
      candidates" due to their comorbidities. MitraClip is a new percutaneous approach
      for treating mitral valve regurgitation which involves mechanical edge-to-edge
      coaptation of the mitral leaflets. In October of 2013, The US Food and Drug
      Administration (FDA) approved the MitraClip for patients with symptomatic
      degenerative mitral regurgitation deemed high risk for mitral-valve surgery.
      Several large clinical trials confirmed the safety and efficacy of MitraClip. We
      here discuss the growing role of MitraClip, the major clinical trials, the
      ongoing trials and the potential complications of the procedure. 

PMID- 24590503
TI  - Preparation, characterization and in vitro thrombolytic activity of a novel
      streptokinase foam.
AB  - Vascular thrombosis is a potentially fatal disease. Thrombolysis represents an
      efficient therapeutic option, although it still presents intrinsic bleeding
      risks. In order to minimize this problem, intra-thrombus injections, alone or
      associated with some kind of mechanical thrombectomy, have been used. In this
      work, a new approach to thrombolysis is presented, where the preparation,
      characterization and in vitro thrombolytic activity of a novel streptokinase foam
      are reported. Foams were prepared by mixing albumin solution with CO2 at
      different volume ratios. Foam stability and apparent viscosity were the
      parameters used to characterize the foams. The volume ratio between CO2 and
      albumin solution that yielded the samples with the best properties was used to
      prepare the thrombolytic foams, where streptokinase was used as the thrombolytic
      agent. The thrombolytic effect of this foam was assessed in vitro by delivering
      it intra-thrombus and the results were compared with those of the foam without
      streptokinase as well as those of a regular streptokinase solution. Both foam
      stability and viscosity increased as the ratio of CO2:albumin solution increased
      and the 3:1 ratio was used to incorporate streptokinase. The in vitro
      thrombolytic activity study revealed that the streptokinase foam caused a 46.6 %
      of thrombus lysis after 30 min of experiment against 21 and 31 % of those of the
      foam without streptokinase and the regular streptokinase liquid solution,
      respectively. Thus, the use of CO2:albumin foam enhanced the in vitro
      thrombolytic effect of streptokinase, which indicates its potential as a novel
      vehicle for carrying and delivering streptokinase to targeted thrombi. 

PMID- 24590505
TI  - How much tetraradical character is present in the Si6Ge9 cluster?
AB  - This study discusses in detail the supposedly tetraradicaloid nature of a
      spirobis(pentagerma[1.1.1]propellane) derivative recently reported by Ito et al.
      (J. Am. Chem. Soc., 2013, 135, 6770). The electronic structure properties of the
      Si6Ge9 cluster are computationally explored by means of the composition of the
      ground state wavefunction, excitation energies to low-lying singlet, triplet and
      quintet states, and magnetic couplings between radical centers. Two main
      conclusions can be extracted from the obtained results regarding the radical
      character of spriobis(pentagerma[1.1.1]propellane): (i) the ground state of the
      Si6Ge9 cluster presents a rather small amount of effective unpaired electrons,
      which might be related to its chemical stability and (ii) there is in fact a
      perceptible tetraradical character within the small overall radical nature of the
      molecule. The proposed description do not contradict the conclusions drawn by the
      introductory work of Ito et al., but it provides a more detailed and precise
      interpretation of radical character of the molecule.

PMID- 24590504
TI  - Electrochemical post-functionalization of conducting polymers.
AB  - This article summarizes recent progress in the post-functionalization of
      conjugated polymers by electrochemical methods. These electrochemical polymer
      reactions typically proceed via electrochemical doping of a conjugated polymer
      film, followed by chemical transformation. Examples include the quantitative
      oxidative fluorination of polyfluorenes and oxidative halogenation of
      polythiophenes, as well as the reductive hydrogenation of polyfluorenones. The
      degree of functionalization, otherwise known as the reaction ratio, can be
      controlled by varying the charge passed through the polymer, allowing the
      optoelectronic properties of the conjugated polymers to be tailored. Wireless
      bipolar electrodes with an in-plane potential distribution are also useful with
      regard to the electrochemical doping and reaction of conjugated polymers and
      allow the synthesis of films exhibiting composition gradients. Such bipolar
      electrochemistry can induce multiple reaction sites during electrochemical
      polymer reactions. 

PMID- 24590506
TI  - Development of a method that eliminates false-positive results due to nerve
      growth factor interference in the assessment of fulranumab immunogenicity.
AB  - Fulranumab, a human IgG2 monoclonal antibody that neutralizes nerve growth factor
      (NGF), is currently in development for the treatment of pain. Our initial
      immunogenicity test method was found to be prone to NGF interference, leading to
      a high apparent incidence of anti-drug antibody (ADA) in phase 1 studies. The ADA
      immunoassay comprised a homogeneous bridging electrochemiluminescence (ECL)
      format with biotin and ruthenium-labeled fulranumab bound together ("bridged") by
      ADA in test samples for detection. In this assay, NGF produced a false-positive
      signal due to its ability to bridge fulranumab molecules. Thus, we developed a
      specificity assay to eliminate the NGF false-positive results. We encountered the
      challenge of eliminating drug interference as well as drug target interference,
      and discovered that the acid-dissociation-based pretreatment of samples used for
      mitigating drug interference dramatically increased drug target interference.
      Several strategies were investigated to eliminate the NGF interference; yet only
      one strategy specifically removed NGF and produced true fulranumab-specific ADA
      results by using competitive inhibition with fulranumab and utilizing an
      alternative NGF binding antibody to eliminate NGF interference. Using this new
      method, we confirmed that the high apparent anti-fulranumab antibody incidence
      (>60%) in clinical study samples was in fact due to fulranumab-bound NGF released
      during the acid-dissociation step of the ADA testing method. We conclude that our
      revised method accurately identifies anti-fulranumab antibodies by incorporating
      steps to eliminate fulranumab and NGF interference. We advise that acid
      dissociation pretreatment must not be universally applied to improve ADA assays
      without investigating its bioanalytical risks versus benefits. 

PMID- 24590508
TI  - New synthesis: parallels between biodiversity and chemodiversity.

PMID- 24590507
TI  - Emotion regulation difficulties in anorexia nervosa before and after inpatient
      weight restoration.
AB  - OBJECTIVE: This study examined: (1) changes in emotion regulation difficulties in
      underweight inpatients with anorexia nervosa (AN) following weight restoration,
      (2) differences in emotion regulation between AN subtypes at acute and weight
      restored stages of illness. METHOD: Repeated measure analyses of variance
      examined changes in scores on the Difficulties in Emotion Regulation Scale (DERS;
      Gratz and Roemer, J Psychopathol Behav Assess, 26, 41-54, 2004) and other
      clinical variables in a group of inpatients with AN from hospital admission (N =
      65) to weight restoration (N = 51). Correlations between BMI and DERS scores at
      both time points were examined. Emotion regulation difficulties were compared
      between individuals with AN, restricting type (AN-R) and AN, binge/purge type (AN
      BP) at both time points using multivariate analysis of covariance. RESULTS: All
      clinical variables, except for the DERS, significantly improved with weight
      restoration (p < .001). There were no associations between BMI and DERS prior to
      or after weight restoration and AN subtypes did not significantly differ in
      emotion regulation difficulties. DISCUSSION: Unlike other clinical variables,
      emotion regulation difficulties in AN did not improve with weight restoration. In
      addition, both subtypes of AN appear to have similar difficulties with emotion
      regulation. The treatment of AN might be enhanced by focusing on improving
      emotion regulation abilities.

PMID- 24590509
TI  - T-type calcium channels in chronic pain: mouse models and specific blockers.
AB  - Pain is a quite frequent complaint accompanying numerous pathologies. Among these
      pathological cases, neuropathies are retrieved with identified etiologies
      (chemotherapies, diabetes, surgeries...) and also more diffuse syndromes such as
      fibromyalgia. More broadly, pain is one of the first consequences of the majority
      of inherited diseases. Despite its importance for the quality of life, current
      pain management is limited to drugs that are either old or with a limited
      efficacy or that possess a bad benefit/risk ratio. As no new pharmacological
      concept has led to new analgesics in the last decades, the discovery of
      medications is needed, and to this aim the identification of new druggable
      targets in pain transmission is a first step. Therefore, studies of ion channels
      in pain pathways are extremely active. This is particularly true with ion
      channels in peripheral sensory neurons in dorsal root ganglia (DRG) known now to
      express unique sets of these channels. Moreover, both spinal and supraspinal
      levels are clearly important in pain modulation. Among these ion channels, we and
      others revealed the important role of low voltage-gated calcium channels in
      cellular excitability in different steps of the pain pathways. These channels, by
      being activated nearby resting membrane potential have biophysical
      characteristics suited to facilitate action potential generation and rhythmicity.
      In this review, we will review the current knowledge on the role of these
      channels in the perception and modulation of pain. 

PMID- 24590510
TI  - Functional network analysis of obese and lean Gottingen minipigs elucidates
      changes in oxidative and inflammatory networks in obese pigs.
AB  - The Gottingen minipig model of obesity is used in pre-clinical research to
      predict clinical outcome of new treatments for metabolic diseases. However,
      treatment effects often remain unnoticed when using single parameter statistical
      comparisons due to the small numbers of animals giving rise to large variation
      and insufficient statistical power. The purpose of this study was to perform a
      correlation matrix analysis of multiple multi-scale parameters describing co
      segregation of traits in order to identify differences between lean and obese
      minipigs. More than 40 parameters, ranging from physical, cardiovascular,
      inflammatory and metabolic markers were measured in lean and obese animals.
      Correlation matrix analysis was performed using permutation test and
      bootstrapping at different levels of significance. Single parameter comparisons
      yielded significant differences between lean and obese animals mainly for known
      physical traits. On the other hand, functional network analysis revealed new co
      segregations, particularly in the domain of inflammatory and oxidative stress
      markers in the obese animals that were not present in the lean. Functional
      networks of lean or obese minipigs could be utilised to assess drug effects and
      predict changes in parameters with a certain degree of precision, on the basis of
      the networks confidence intervals. Comparison of functional networks in minipigs
      with those of human clinical data may be used to identify common parameters or co
      segregations related to obesity between animal models and man.

PMID- 24590511
TI  - HIV-associated multicentric Castleman's disease after initiation of
      antiretroviral therapy: experience of a European centre.

PMID- 24590512
TI  - Differences in nuclear DNA organization between lymphocytes, Hodgkin and Reed
      Sternberg cells revealed by structured illumination microscopy.
AB  - Advances in light microscopy have enabled the visualization of DNA in the
      interphase nucleus with more detail than is visible with conventional light
      microscopy. The nuclear architecture is assumed to be different in cancer cells
      compared to normal cells. In this paper we have studied, for the first time, the
      organization of nuclear DNA and that of DNA-free space in control lymphocytes,
      Hodgkin cells and Reed-Sternberg cells using 3D structured illumination
      microscopy (SIM). We have observed detail in these SIM images that was not
      observed in conventional widefield images. We have measured the size distribution
      of the DNA structure using granulometry and noted a significant, progressive
      increase in the amount of sub-micron structures from control lymphocytes to
      Hodgkin cells to Reed-Sternberg cells. The DNA-free space changes as well;
      "holes" in the DNA distribution start to appear in the malignant cells. We have
      studied whether these "holes" are nucleoli by staining for upstream binding
      factor (UBF), a protein associated with the nucleolus. We have found that the
      relative UBF content progressively and significantly decreases-or is absent-in
      the DNA-free space when measured as either the Pearson correlation coefficient
      with the DNA-free space or as the number of "holes" that contain UBF. Similar
      differences exist within the population of Reed-Sternberg cells between
      binucleated and multinucleated cells with four or more subnuclei. To our
      knowledge, this is the first study that investigates the changes of the nuclear
      DNA structure in any disease with superresolution light microscopy.

PMID- 24590513
TI  - Apparent diffusion coefficient as a potential surrogate marker for Ki-67 index in
      mucinous breast carcinoma.
AB  - PURPOSE: To examine the association between apparent diffusion coefficient (ADC),
      cellularity, and Ki-67 index in mucinous breast carcinoma (MBC) compared with
      invasive carcinoma of no special type (NST). ADC's ability to identify lesions
      with highly proliferating MBC was also examined. MATERIALS AND METHODS:
      Pathologically confirmed MBCs (mucinous group, n = 18) and NSTs (control group, n
      = 18) were retrospectively analyzed. ADC was calculated from signal intensity of
      diffusion-weighted imaging at b values of 0 and 1000 sec/mm(2) . The Ki-67 index
      and cellularity were histopathologically evaluated. The mucinous group was
      classified into high Ki-67 mucinous group (Ki-67 index >=14%, highly
      proliferating) and low Ki-67 mucinous group. RESULTS: In the mucinous group,
      minimum ADC (ADCmin) showed an inverse correlation with cellularity (r = -0.802,
      P < 0.0001) and Ki-67 index (r = -0.825, P < 0.0001). In the control group,
      ADCmin showed inverse correlation with cellularity (r = -0.537 P = 0.022), but no
      correlation with Ki-67 index (r = 0.035, P = 0.892). ADCmin of high Ki-67
      mucinous group was significantly lower than that of low Ki-67 mucinous group (P =
      0.005). CONCLUSION: This study demonstrates an inverse correlation between ADC
      and Ki-67 index in MBC and the ability of ADC to identify highly proliferating
      MBC. Considering that ADC can evaluate whole lesions noninvasively, ADC may be a
      promising noninvasive surrogate marker for Ki-67 index in the risk stratification
      of MBC.

PMID- 24590515
TI  - Successful application of ex vivo expanded human autologous oral mucosal
      epithelium for the treatment of total bilateral limbal stem cell deficiency.
AB  - Ocular surface reconstruction with ex vivo expanded limbal stem cells (LSCs) is a
      widely used clinical treatment for patients with limbal stem cell deficiency
      (LSCD). This is not applicable to patients with bilateral LSCD where there are no
      remaining LSCs. Cultivated oral mucosa epithelium (OME) has been used as an
      alternative source of autologous epithelial stem cells for ocular reconstruction
      in few clinical trials. However, successful generation of stratified OME
      epithelium has only been achieved in the presence of animal feeder cells and/or
      animal-derived products in the culture media, likely to contribute to increased
      risk of pathogen transmission and graft rejection. In this study, we report
      generation of multilayered OME epithelium that shares many of the characteristics
      of corneal epithelium using a fully compliant good manufacturing practice, feeder
      and animal product-free method. Proof of concept was achieved by transplantation
      of autologous ex vivo expanded OME in two patients with histologically confirmed
      bilateral total LSCD that resulted in successful reversal of LSCD in the treated
      eye up to 24 months.

PMID- 24590514
TI  - Fear of past abusive partner(s) impacts current posttraumatic stress among women
      experiencing partner violence.
AB  - This study examines the impact of fear of past abusive partner(s) on
      posttraumatic stress among 212 community-recruited women currently exposed to
      intimate partner violence (IPV). The path analysis model tested explained 60% of
      the variation in IPV-related posttraumatic stress. Findings revealed that fear of
      past abusive partner(s) was uniquely associated with the severity of current
      posttraumatic stress symptoms over and above the impact of current IPV or
      childhood abuse and neglect. Future research should continue examining women's
      subjective emotional experience of past and current victimization so as to
      further inform both clinical practice and intervention planning. 

PMID- 24590516
TI  - Simulation techniques in the anatomy curriculum: review of literature.
AB  - Modern medical education faces a problem of combining the latest technology,
      procedures and information with classic teaching methods. Simulation is a
      technique, which replaces or amplifies doctor-patient experiences in controlled
      conditions and therefore evokes or replicates substantial aspects of the real
      world in a fully interactive manner. The basic course of anatomy in medical
      education could be recognised as the best example of implementing new educational
      techniques such as simulation, into the traditional medical curriculum. The
      PubMed database was searched using specific key words. Finally 72 articles were
      accepted and were divided into 3 basic categories of teaching methods: Category 1
      - cadaveric dissection, Category 2 - simulator based education and Category 3 -
      other. A state of the art anatomical curriculum offers numerous possibilities and
      solutions including the oldest like cadaveric dissection and newest like
      simulators. Different simulation techniques are used with different intensity;
      however cadaveric dissection is still the most popular method. The second most
      frequent method is simulation-based training, in which North America is the
      leading country. The identification of anatomical structures during virtual
      surgical procedures or laparoscopic robotic procedures can be integrated into the
      traditional anatomy course. New technologies are supportive and beneficial in
      anatomy teaching however each excitement of new technologies sometimes should be
      tempered and evaluated for its usefulness in making the learning process
      constructive for students and their future practice. 

PMID- 24590517
TI  - Morphological and radiometrical study of the human intervertebral foramina of the
      cervical spine.
AB  - BACKGROUND: Degenerative changes of the cervical spine are an inevitable response
      to certain occupational status and aging processes. Compression of cervical nerve
      roots may result from disc degeneration, disc herniation or intervertebral
      foraminal stenosis. The precise and detailed anatomical knowledge of the
      intervertebral foramen of the cervical spine is essential for the diagnosis and
      management of cervical radiculopathy. The significance of the observations and
      findings of the present study was to elucidate the correlation between the
      morphology and disorders of the cervical intervertebral foramina in normal and
      pathological conditions especially at the level of C3-C4 to C6-C7 on both sides
      and in both sexes. Moreover, it will help greatly in the planning of both
      surgical and conservative strategies. MATERIALS AND METHODS: In the present
      study, 5 formalin-fixed adult cadavers and radiological specimens of the cervical
      region of the vertebral column of 28 normal and 209 subjects suffering from
      cervical disorder from both sexes and different age groups. They subjected for
      morphological and radiometrical analysis. RESULTS: All measurements of the
      present study of the cervical disorders in females were found to be 6% less than
      in males in all age groups, which is statistically significant (p < 0.01) as
      compared with the control group (2%). The mean intervertebral foraminal areas in
      the control group of C5-C6 and C6-C7 are significantly greater than those of C3
      C4 and C4-C5. CONCLUSIONS: The mean intervertebral foraminal area was greater in
      the lower cervical region than the upper in normal adult individuals. In
      pathological condition the affection of C3-C4 and C4-C5 intervertebral foramina
      was more due to narrower surface area. The pathology of cervical spine affecting
      the intervertebral foramina of female which complaint earlier than male due to
      narrower foramina.

PMID- 24590518
TI  - Micro-computed tomography study of the abnormal osseous extensions of sella
      turcica.
AB  - The paper presents anatomical considerations on the abnormal ossification, which
      occurred around the dorsum of the sella turcica in the human skull of the female
      individual. Probably the morphological alterations of the sellar region were
      associated with extensive heterotopic ossification of the dura mater attached to
      the dorsum of the sella turcica and the posterior clinoid processes. The analysis
      of gray values of the voxels representing the areas of abnormal ossification
      indicated on variation in bone density in the entire sample. We have established
      that the highest mineralisation of bony tissue occurred in the marginal parts of
      the osseous extensions deriving from the posterior clinoid processes. The
      ossified parts of dura mater attached to the posterior clinoid processes showed
      significantly higher content of the hydroxyapatite (1.9 g/cm3) than the dorsum of
      the sella turcica (1.0 g/cm3). 

PMID- 24590519
TI  - Quantitative analysis of the terminal branches of facial nerve in fresh frozen
      head and neck specimens.
AB  - BACKGROUND: The first aim of this study was the quantification of nerve fibres
      found in terminal branches of facial nerve and the second aim was the
      ultrastructural analysis of these terminal branches in order to observe their
      ultrastructural differences, if present. In the examination of literature; we
      could not find any studies related to this subject. MATERIALS AND METHODS: Four
      fresh frozen head and neck specimens were used and the dissections were done
      bilaterally. Therefore; totally 8 samples were examined. The samples were
      prepared according to routine transmission electron microscopic tissue
      preparation technique. The semi-thin sections were examined under light
      microscope by camera lucida. In every sample, the quantitative analysis was
      performed in 5 different areas in an area of 0.01 mm2 and statistical analysis
      was done. Secondly; the ultrastructural appearance of these terminal branches
      were examined under transmission electron microscope. RESULTS: In the
      quantitative analysis of terminal branches of facial nerve in an area of 0.01
      mm2; the least number of nerve fibres were found in temporal branches and the
      highest number were detected in cervical branches. In transmission electron
      microscopic examination, no significant difference was found in between these
      branches. In the statistical analysis; statistically significant differences were
      obtained in between the temporal and buccal, marginal mandibular, cervical
      branches; zygomatic and marginal mandibular, cervical branches; buccal and
      marginal mandibular, cervical branches; marginal mandibular and cervical
      branches. CONCLUSIONS: These numerical data will have an importance during the
      nerve repair process of terminal branches of facial nerve in various injuries.

PMID- 24590520
TI  - Laryngeal nerve "anastomoses".
AB  - Laryngeal nerves have been observed to communicate with each other and forma
      variety of patterns. These communications have been studied extensively and have
      been of particular interest as it may provide an additional form of innervation
      to the intrinsic laryngeal muscles. Variations noted in incidence may help
      explain the variable position of the vocal folds after vocal fold paralysis. This
      study aimed to examine the incidence of various neural communications and to
      determine their contribution to the innervation of the larynx. Fifty adult
      cadaveric en-bloc laryngeal specimens were studied. Three different types of
      communications were observed between internal and recurrent laryngeal nerves viz.
      (1) Galen's anastomosis (81%):in 13%, it was observed to supply the posterior
      cricoarytenoid muscle; (2) thyroarytenoid communication (9%): this was observed
      to supply the thyroarytenoid muscle in 2% of specimens and (3) arytenoid plexus
      (28%): in 6%, it supplied a branch to the transverse arytenoid muscle. The only
      communication between the external and recurrent laryngeal nerves was the
      communicating nerve (25%). In one left hemi-larynx, the internal laryngeal nerve
      formed a communication with the external laryngeal nerve, via a thyroid foramen.
      The neural communications that exist in the larynx have been thought to play a
      role in laryngeal innervation. The results of this study have shown varying
      incidences in neural communications. Contributions from these communications have
      also been noted to various intrinsic laryngeal muscles which may be a possible
      factor responsible for the variable position of the vocal folds in certain cases
      of vocal fold paralysis.

PMID- 24590521
TI  - Gross morphometry of the heart of the Common marmoset.
AB  - The Callithrix jacchus is a Brazilian endemic species that has been widely used
      as an experimental model in biomedical research. Anatomical data are necessary to
      support experimental studies with this species. Eleven hearts of C. jacchus from
      the German Primate Centre (DPZ) have been studied in order to characterize their
      gross morphometry and compare them with other animal models and human. Biometric
      data were also obtained. The mean values for morphometry of the hearts did not
      show any significant difference between male and female. The relative heart
      weight was similar to human, bovine and equine species. Considering those
      aspects, the C. jacchus could be used as non-human primate experimental model for
      biomedical studies on heart.

PMID- 24590522
TI  - The heart exhibits right to left communication between the fibres of the muscular
      part of the interventricular septum.
AB  - 1900 years ago Galen stated that blood seeps through the perforations in the
      interventricular septum. However, William Harvey, working 400 years ago, failed
      to find any. In this study an aqueous solution of a black dye was gently pumped
      by hand into the right ventricle of 20 porcine hearts. The area in the middle
      ofthe left muscular part of the interventricular septum in 13 of the hearts was
      bloodstained under the endocardium at the time the heart stopped beating. The
      same area of all 20 hearts eventually became stained black. A small amount of
      black dye seeped through the endocardium of 18 hearts in the middle of the left
      muscular part of the interventricular septum. In another 20 porcine hearts
      theinterventricular septa were dissected after boiling. The deep pit under the
      anterior interventricular sulcus communicated with the right ventricle and with
      the middle of the left muscular part of the interventricular septum between the
      fibres of the muscle. The communication closed tight at the very early systole.
      The communication resembled that reported by Galen 1900 years ago. The
      communication may be the real foetal route for diastolic circulation through the
      muscular part of the interventricular septum from right to left. The results
      suggested that the anatomy, function and embryology of the African monkey, human
      and porcine heart are not yet fully understood. 

PMID- 24590523
TI  - Prevalence of congenital coronary artery anomalies and variants in 726
      consecutive patients based on 64-slice coronary computed tomography angiography.
AB  - BACKGROUND: Coronary computed tomography angiography (CCTA) is helpful in making
      a precise noninvasive evaluation of coronary anatomy, allowing concomitant
      evaluation of other cardiac structures. The aim of this study was to determine
      the prevalence of coronary artery variations detected by 64-slice multi detector
      CT. MATERIALS AND METHODS: The results of ECG-gated CCTA in 726 consecutive
      patients (mean age 58 years) were analysed retrospectively. The main indications
      for CCTA were a typical chest pain, angina pectoris, screening for coronary
      artery disease and determination of the patency of bypass grafts or stents.
      Acquisition was performed with a 64-detector CT scanner with retrospective ECG
      gating. Imaging results were assessed by experienced cardiovascular radiologist.
      RESULTS: The overall incidence of coronary artery anomalies was 1.1% (8 out of
      726 participants). The most common anomaly was an anomalous origin of the
      circumflex artery from the right coronary sinus with a retroaortic course (4
      patients,0.6%), followed by origin of right coronary artery from the left
      coronary sinus (2 patients, 0.3%). One patient with abnormal origin of the left
      main artery from the right coronary sinus (0.1%) and 1 patient with a circumflex
      artery origin from the proximal segment of the right coronary artery (0.1%) were
      observed, both with retroartic course. CONCLUSIONS: CCTA is a noninvasive imaging
      technique useful for the precise evaluation of variations of the coronary
      arteries. This study shows similar results to other reports on this subject.

PMID- 24590524
TI  - Origin of profunda femoris artery and its circumflex femoral branches: anatomical
      variations and clinical significance.
AB  - BACKGROUND: Knowledge of the anatomical variations of the profunda femoris artery
      and its circumflex branches is important during angiographic diagnostic
      procedures as well as during performing surgery in the femoral region. The aim of
      this study was to examine the original sites, distances and variations of the
      profunda femoris artery and its circumflex branches. MATERIALS AND METHODS: The
      study was conducted in the Department of Anatomy, Faculty of Medicine, King
      Abdulaziz University from October, 2011 to May, 2013 after the approval of the
      medical ethical committee. Dissections of 90 femoral triangles of 25 male and 20
      female adult human cadavers were performed to demonstrate the origin and
      distribution of the profunda femoris artery and its circumflex branches. RESULTS:
      The profunda femoris artery mostly originated from the posterolateral aspect of
      the femoral artery in 42% of male limbs and in 42.5% of female limbs, from the
      posterior side in 24% of male and 27.5% of female limbs, from the lateral side in
      20% of males and female limbs and from the posteromedial aspect in 14% of male
      limbs and in 7.5% of female limbs. The mean distance of origin of profunda
      femoris artery from the midpoint of inguinal ligament was 51.5 +/- 1.9 mm in
      right male, 49.7 +/- 1.9 mm in left male, 48.5 +/- 2.2 mm in right female and
      48.9 +/- 2.2 mm in left female limbs. The medial and lateral circumflex arteries
      originated mostly from the profunda femoris artery (60% in males; 57.7% in
      females) at a mean distance of 18.6 +/- 2.1 mm and 20.2 +/- 2.2 mm in right male,
      19.6 +/- 1.9 mm and 22.5 +/- 2.3 mm in left male, 18.8 +/- 2.7 mm and 21 +/- 2.6
      mm in right female and 19.1 +/- 2.1 mm and 21.7 +/- 2.6 mm in left female limbs,
      respectively. The original incidence of the medial and lateral circumflex femoral
      arteries from the femoral artery including the common trunk was 40% in male and
      42.3% in female limbs. CONCLUSIONS: Awareness of the original sites and distances
      of the profunda femoris artery and its circumflex femoral branches will allow the
      surgeon to define the vascular pattern before performing any invasive procedure
      and to avoid unexpected iatrogenic injuries.

PMID- 24590525
TI  - Human adult dental pulp CD117/c-kit-positive networks of stromal cells.
AB  - Dental pulp tissue was collected from 6 healthy adult patients, prior to
      prosthetic treatments, in order to evaluate the in situ phenotype of dental pulp
      stromal cells and compare with that of dental pulp stem cells. A CD34
      /CD44+/CD105-/CD117+/CD146-/nestin- phenotype of stromal cells in the dental pulp
      core was found. Cells with a similar phenotype, but CD44-, were found in the cell
      richzone. Dental pulp stromal networks (DPSNs) were found CD117+/CD44+ in the
      pulp core, but CD117+/CD44- in the cell rich zone. The c-kit-positive DPSNs were
      contacting pulp nerves and were, in this regard only, comparable to interstitial
      Cajal cells. Stromal signalling in dental pulp needs further evaluation, in
      normal tissue as well as a possible cause of persisting pain after endodontic
      treatments.

PMID- 24590526
TI  - Role of the superior turbinate when performing endoscopic endonasal
      transsphenoidal approach.
AB  - BACKGROUND: This study examined the relationship between the superior turbinate
      and natural ostium of the sphenoid sinus, as seen during the endoscopic endonasal
      transsphenoidal approach (EETSA) for sellar lesions and described how to enter
      the sphenoethmoid cell safely for complete exposure of the sellar floor,
      including adjacent vital structures such as the prominence of the optic nerve and
      carotid artery. MATERIALS AND METHODS: This study retrospectively reviewed the
      medical records and operative findings of 154 patients, who underwent EETSA
      between February 2009 and February 2011. We evaluated the location of the natural
      ostium of the sphenoid sinus relative to the superior turbinate and revealed the
      clinical significance of the superior turbinate as a surgical guide to enter into
      the sphenoethmoid cell during EETSA. RESULTS: The natural ostium of the sphenoid
      sinus was located medially to the posteroinferior end of the superior turbinate
      in 151 (98%) patients. In 1 patient, the natural ostia of the sphenoid sinus were
      located lateral to the superior turbinate bilaterally. Sphenoethmoid cell was
      encountered in 53 (34%) patients. We could easily enter the sphenoethmoid cell at
      the point where the superior turbinate was attached to the anterior wall of the
      sphenoid sinus. CONCLUSIONS: The superior turbinate is a good surgical landmark
      for identifying the natural ostium of the sphenoid sinus and as a guide for the
      surgical entrance to the sphenoethmoid cell extending to the sphenoid sinus
      during EETSA.

PMID- 24590527
TI  - Morphology of the bicipital aponeurosis: a cadaveric study.
AB  - The bicipital aponeurosis (BA) is a fascial expansion which arises from the
      tendon of biceps brachii and dissipates some of the force away from its enthesis.
      It helps in dual action of biceps brachii as supinator and flexor of forearm. The
      aim of the present work was to study the morphology of BA. Thirty cadavericupper
      limbs (16 right and 14 left side limbs) were dissected and dimensions ofthe BA
      were noted. The average width of aponeurosis at its commencement on the right was
      15.74 mm while on the left it was 17.57 mm. The average angle between tendon and
      aponeurosis on the right was 21.16 degrees  and on the left it was 21.78 degrees
      . The fibres from the short head of the biceps brachii contributed to the
      formation of proximal part of aponeurosis. Fascial sheath over the tendon oflong
      head of biceps brachii was seen to form the distal part of the aponeurosis. In 5
      cases, large fat globules were present between the sheath and the tendon.
      Histologically: The aponeurosis showed presence of thick collagen bundles.
      Fascials heath covering the tendon of long head extended towards the aponeurosis
      and passed superficial to the tendon of biceps. Blood vessels and adipose tissue
      were found to be present between fascial sheath and the tendon. This
      morphological description of BA may be helpful 1) in elucidating the dynamic role
      that BA plays in normal functioning and 2) to the surgeons in the repair of
      ruptured biceps brachii tendon. 

PMID- 24590528
TI  - Fenestration of the vertebral artery: case presentation.
AB  - Fenestrations of vertebral arteries are considered to be rare abnormalities
      observed in angiographic and autopsy studies. They result from vascular
      abnormalities that occur during the embryological development of vertebral
      artery. Fenestrations of the vertebral artery are vascular structures having 2
      different lumens and endothelium layers, sharing either the same or separate
      adventitia layers. As a result of the carotid Doppler ultrasonography performed
      on a 65-year-old woman applying to the Neurology Clinic of Cumhuriyet University
      Faculty of Medicine, Research and Practice Hospital with the complaints of
      vertigo and numbness in the head, a plaque leading to 60% stenosis in the right
      internal carotid artery, close to the place of initiation was seen. The patient,
      whose vertebral artery lumen structures and calibrations have found to be normal
      in the Doppler ultrasonography of vertebral artery, was scheduled for double
      sided selective carotid and vertebral artery angiography. With the performed
      digital subtraction angiography imaging method, an atheroma plaque, extending to
      internal carotid artery proximal starting from sinus caroticus through the right
      internal carotid artery and leading to 50% stenosis, having the appearance of an
      ulcer, was observed. In the vertebral artery angiography of the case, while the
      right vertebral artery was found to be normal, fenestration in the upper cervical
      segment was observed in the left vertebral artery. This situation has been
      presented in this paper with radiological and embryological evaluation.

PMID- 24590529
TI  - Unilateral absence of foramen spinosum with bilateral ophthalmic origin of the
      middle meningeal artery: case report and review of the literature.
AB  - Bilateral ophthalmic origin of the middle meningeal artery with an unilateral
      absence of foramen spinosum has not yet been described. We report on a skull with
      endocranial meningeal grooves indicating bilateral ophthalmic origin of the
      middle meningeal artery, however, its branches were normal both in their position
      and distribution. In addition, a rare venous sinus variation was present
      unilaterally - a sinus of Hyrtl. Imaging identification of the anomalous origin
      of the middle meningeal artery is important while planning surgical and
      endovascular interventions in the middle cranial fossa and the orbit. 

PMID- 24590530
TI  - The scaphocephalic skull of an adult male.
AB  - The paper presents abnormal craniofacial morphology of an adult male afflicted
      with premature closure of the sagittal suture. The skull is well preserved and
      there are no visible traits of surgical management which would be aimed to
      correctcranial deformation. In consequence of the restricted cranial development,
      some diameters of the skull were significantly altered. Basically, cranial vault
      morphology fits apparently to the scaphocephaly, whereas the basic ranium and
      viscerocranium are altered only in minor degree. 

PMID- 24590531
TI  - Inferior vena cava hypoplasia with right hepatic vein and accessory inferior
      hepatic vein shunt.
AB  - Inferior vena cava (IVC) hypoplasia is a rare condition. Venous blood flow is
      usually provided through collaterals in the azygos or hemiazygos venous systems.
      However, portosystemic shunts with intrahepatic venous collateral are extremely
      rare. The case is presented here of a large shunt between the right hepatic vein,
      accessory inferior hepatic vein, and inferior vena cava in a 37-year-old female
      patient with IVC hypoplasia. 

PMID- 24590532
TI  - Vortex-pattern self-assembly in Mn-doped ZnSe nanorods.
AB  - Spontaneous patterning of anisotropic nanostructures into ordered assemblies
      remains a challenging quest, which requires controlled innovative approaches. One
      way to achieve such ordering of 1D nanorods is by manipulating the varieties of
      interactions (attractive and repulsive forces) present in colloidal solutions of
      anisotropic nanocrystals. The other ingenuous pathway is solvent-evaporation
      mediated self-organization of the 1D nanorods. By following the second protocol,
      we have achieved exclusive pillar self-assembled patterns of visible-light
      emitting Mn-doped ZnSe nanorods. The nanorods also exhibit intriguing vortex
      patterning observed by directional solvent evaporation from the nanorod solution.
      The effect of solvent evaporation to generate such unique morphologies on the TEM
      grid is discussed and the reported procedure to obtain the assembled patterns of
      visible-light-emitting, doped nanorods might be useful for future technological
      applications. 

PMID- 24590534
TI  - Assessment of genetic diversity and conservation priority of Omani local chickens
      using microsatellite markers.
AB  - Designing strategies for conservation and improvement livestock should be based
      on assessment of genetic characteristics of populations under consideration. In
      Oman, conservation programs for local livestock breeds have been started. The
      current study assessed the genetic diversity and conservation potential of local
      chickens from Oman. Twenty-nine microsatellite markers were analyzed in 158 birds
      from six agro-ecological zones: Batinah, Dhofar, North Hajar, East Hajar,
      Musandam, and East Coast. Overall, a total of 217 alleles were observed. Across
      populations, the average number of alleles per locus was 7.48 and ranged from 2
      (MCW98 and MCW103) to 20 (LEI094). The mean expected heterozygosity (H E) was
      0.62. Average fixation index among populations (F ST) was 0.034, indicating low
      population differentiation, while the mean global deficit of heterozygotes across
      populations (F IT) was 0.159. Based on Nei's genetic distance, a neighbor-joining
      tree was constructed for the populations, which clearly identified the Dhofar
      population as the most distant one of the Omani chicken populations. The analysis
      of conservation priorities identified Dhofar and Musandam populations as the ones
      that largely contribute to the maximal genetic diversity of the Omani chicken
      gene pool.

PMID- 24590535
TI  - Favorable outcomes of tacrolimus compared with cyclosporine A for GVHD
      prophylaxis in HSCT for standard-risk hematological diseases.
AB  - Although calcineurin inhibitors (CNIs) with short-term methotrexate (stMTX)
      constitute standard prophylaxis for graft-versus-host diseases (GVHD) in
      hematopoietic stem cell transplantations (HSCT), comparative efficacy of
      cyclosporine A (CsA) and tacrolimus (Tac) still remains unclear. We have altered
      GVHD prophylaxis for standard-risk hematological malignancies from CsA (target
      trough level, 500 ng/mL) to Tac (15 ng/mL) both with stMTX in May 2008, enabling
      us to compare the efficacy of CNIs with little selection biases. The cumulative
      incidence of acute and chronic GVHD was comparable for CsA and Tac. Among the
      GVHD low-risk patients who received stem cells from matched sibling donors or
      cord blood, the Tac arm had a trend for favorable control of grade III-IV acute
      GVHD (6.7 vs. 30.0 %, p = 0.2), which may contribute to the significantly better
      overall survival (p = 0.048) and relapse-free survival (p = 0.043) in that group.
      Inadequate concentration of CNIs in early phase of HSCT affected the cumulative
      incidence of acute GVHD in the CsA but not in the Tac arm. There were no
      differences in the GVHD incidence and survival outcomes between CsA and Tac in
      the GVHD high-risk subgroup. This study underlies the significance of maintaining
      adequate CsA concentration in standard-risk HSCT. 

PMID- 24590536
TI  - Serum albumin retains independent prognostic significance in diffuse large B-cell
      lymphoma in the post-rituximab era.
AB  - Serum albumin (SA) has been shown to be a prognostic marker in many hematological
      malignancies and in diffuse large B-cell lymphoma (DLBCL) prior to chemo
      immunotherapy. SA may be a surrogate for age, comorbid status, and disease
      severity. Here, we aimed to assess whether SA can be an independent prognostic
      marker in patients with newly diagnosed DLBCL treated with rituximab,
      cyclophosphamide, vincristine, doxorubicin, and prednisone (R-CHOP). Patients who
      presented at the Moffitt Cancer Center from 2007 to 2010 for DLBCL diagnosis or
      treatment were identified using our institutional database. Clinical and
      treatment data were recorded, including SA levels at diagnosis. Survival time was
      estimated using the Kaplan-Meier method, with Cox proportional hazard model used
      to identify potential risk factors for time-to-event data. From 295 identified
      patients, 171 were excluded for not having primary treatment at our institution
      or not having R-CHOP treatment. In 124 included patients (mean age at diagnosis
      of 58 years, 91 % Caucasian), 25 % were categorized as poor by the revised
      International Prognostic Index. Overall and progression-free survival at 4 years
      were 65 % (95 % CI 57-75) and 58 % (95 % CI 0.49-0.69), respectively. Using
      multivariate analysis, we found that the hazard index of death of patients with
      SA >=3.7 g/dL was 26 % (95 % CI 13-53) of the hazard for those patients who had
      SA <3.7 g/dL when controlling for the revised International Prognostic Index risk
      and initial lymphocyte count. Our study shows that SA >=3.7 g/dL is an
      independent prognostic marker in DLBCL patients treated with R-CHOP.

PMID- 24590539
TI  - Arrest of rolling circle amplification by protein-binding DNA aptamers.
AB  - Certain DNA polymerases, such as phi29 DNA polymerase, can isothermally copy the
      sequence of a circular template round by round in a process known as rolling
      circle amplification (RCA), which results in super-long single-stranded (ss) DNA
      molecules made of tandem repeats. The power of RCA reflects the high processivity
      and the strand-displacement ability of these polymerases. In this work, the
      ability of phi29DNAP to carry out RCA over circular templates containing a
      protein-binding DNA aptamer sequence was investigated. It was found that protein
      aptamer interactions can prevent this DNA polymerase from reading through the
      aptameric domain. This finding indicates that protein-binding DNA aptamers can
      form highly stable complexes with their targets in solution. This novel
      observation was exploited by translating RCA arrest into a simple and convenient
      colorimetric assay for the detection of specific protein targets, which continues
      to showcase the versatility of aptamers as molecular recognition elements for
      biosensing applications. 

PMID- 24590540
TI  - Ghent Pathology 2011.
AB  - This study examines the intraday formation process of transaction prices and bid
      ask spreads in theKOSPI 200 futures market. By extending the structural model
      ofMadhavan,Richardson, andRoomans (1997), I develop a unique cross-market model
      that can decompose spread components and explain intraday price formation for the
      futures market by using the order flow information from theKOSPI 200 options
      market, which is a market that is closely related to the futures market as well
      as considered to be one of the most remarkable options market in the world. The
      empirical results indicate that the model implied spread and the permanent
      component of the spread that results from informed trading tend to be
      underestimated without the inclusion of options market information. Furthermore,
      the results imply that trades of in-the-money options, which have high delta
      values, generally incur a more adverse information cost component (the permanent
      spread component) of the futures market than those of out-of-the-money options,
      which have relatively low delta values. Finally, I find that the adverse
      information cost component that is estimated from the cross-market model exhibits
      a nearlyU-shape intraday pattern; however, it sharply decreases at the end of the
      trading day.

PMID- 24590541
TI  - A reconsideration and response to Parrott AC (2013) "Human psychobiology of MDMA
      or 'Ecstasy': an overview of 25 years of empirical research".
AB  - Parrott recently published a review of literature on MDMA/ecstasy. This
      commentary is a response to the content and tenor of his review, which
      mischaracterizes the literature through misstatement and omission of contrary
      findings, and fails to address the central controversies in the literature. The
      review makes several erroneous statements concerning MDMA-assisted psychotherapy,
      such as incorrect statements about research design and other statements that are
      baseless or contradicted by the literature. Though it critiques an attempt by
      other authors to characterize the risks of MDMA, the review fails to produce a
      competing model of risk assessment, and does not discuss potential benefits.
      Parrott does not represent an even-handed review of the literature, but instead
      recites dated misconceptions about neurotoxicity concerns involving the
      recreational drug ecstasy, which do not relate directly to the use of pure MDMA
      in a therapeutic setting. Unchallenged, Parrott's report may deter researchers
      from further investigating an innovative treatment that in early clinical trials
      has demonstrated lasting benefits for people with chronic, treatment-resistant
      post-traumatic stress disorder.

PMID- 24590542
TI  - MDMA is certainly damaging after 25 years of empirical research: a reply and
      refutation of Doblin et al. (2014).
AB  - Human Psychopharmacology recently published my review into the increase in
      empirical knowledge about the human psychobiology of MDMA over the past 25 years
      (Parrott, 2013a). Deficits have been demonstrated in retrospective memory,
      prospective memory, higher cognition, complex visual processing, sleep
      architecture, sleep apnoea, pain, neurohormonal activity, and psychiatric status.
      Neuroimaging studies have shown serotonergic deficits, which are associated with
      lifetime Ecstasy/MDMA usage, and degree of neurocognitive impairment. Basic
      psychological skills remain intact. Ecstasy/MDMA use by pregnant mothers leads to
      psychomotor impairments in the children. Hence, the damaging effects of
      Ecstasy/MDMA were far more widespread than was realized a few years ago. In their
      critique of my review, Doblin et al. (2014) argued that my review contained
      misstatements, omitted contrary findings, and recited dated misconceptions. In
      this reply, I have answered all the points they raised. I have been able to
      refute each of their criticisms by citing the relevant empirical data, since many
      of their points were based on inaccurate summaries of the actual research
      findings. Doblin and colleagues are proponents of the use of MDMA for drug
      assisted psychotherapy, and their strongest criticisms were focused on my
      concerns about this proposal. However, again all the issues I raised were based
      on sound empirical evidence or theoretical understanding. Indeed I would
      recommend potentially far safer co-drugs such as D-cycloserine or oxytocin. In
      summary, MDMA can induce a wide range of neuropsychobiological changes, many of
      which are damaging to humans.

PMID- 24590543
TI  - Effects of antipsychotic drugs on cardiovascular variability in participants with
      bipolar disorder.
AB  - OBJECTIVE: The risk for cardiovascular diseases is elevated in persons with
      bipolar disorder. However, it remains unknown how much of this excess risk is
      secondary to pharmacologic treatment. We tested the hypothesis that current and
      cumulative antipsychotic drug exposure is associated with increased
      cardiovascular risk as indicated by lower heart rate variability (HRV) and
      increased blood pressure variability (BPV). METHODS: Fifty-five individuals with
      bipolar disorder (33 +/- 7 years; 67% female) underwent noninvasive
      electrocardiogram assessment of time-domain and frequency-domain HRV, as well as
      BPV analysis. Medication histories were obtained through systematic review of
      pharmacy records for the past 5 years. RESULTS: Current antipsychotic exposure
      was associated with lower standard deviation of NN intervals. Second-generation
      antipsychotics were associated with lower standard deviation of NN intervals and
      root mean square of successive differences. There was no significant relationship
      between 5-year antipsychotic exposure and HRV in subjects with bipolar disorder.
      Exploratory analysis revealed a possible link between selective serotonin
      reuptake inhibitor exposure and increased low-frequency spectral HRV.
      CONCLUSIONS: Current antipsychotic use (particularly second-generation
      antipsychotics with high affinities for the D2S receptor) is associated with
      reduced autonomic-mediated variability of the HR. The absence of an association
      with cumulative exposure suggests that the effects are acute in onset and may
      therefore relate more to altered autonomic function than structural
      cardiovascular abnormalities. Future studies should prospectively examine effects
      of these antipsychotics on autonomic function.

PMID- 24590544
TI  - Microarray analysis of global gene expression in leukocytes following lithium
      treatment.
AB  - OBJECTIVES: To elucidate the molecular effects of lithium, we studied global gene
      expression changes induced by lithium in leukocytes from healthy subjects.
      METHODS: Eight healthy male subjects participated in this study. Lithium was
      prescribed for weeks to reach a therapeutic serum concentration. Leukocyte counts
      and serum lithium concentrations were determined at baseline (before medication),
      after 1 and 2 weeks of medication and at 2 weeks after stopping medication. Gene
      expression profiling was performed at each time point using Agilent G4112F Whole
      Human Genome arrays (The Agilent Technologies, Santa Clara, CA, USA). Expression
      of some candidate genes was also assessed by real-time polymerase chain reaction
      (PCR). RESULTS: Gene ontology analysis revealed that the cellular and immune
      responses to stimulus and stress indeed played a major role in the cellular
      response to lithium treatment. Pathway analysis revealed that the interleukin 6
      pathway, the inhibitor of differentiation pathway, and the methane metabolism
      pathway were regulated by lithium. Using real-time PCR, we also confirmed that
      five candidate genes in these pathways were significantly changed, including
      suppressor of cytokine signaling 3 and myeloperoxidase. CONCLUSIONS: Our
      investigation suggests that the molecular action of lithium is mediated in part
      by its effects on the cellular and immune response to stimulus and stress
      followed by the interleukin 6, inhibitor of differentiation, and methane
      metabolism pathways.

PMID- 24590545
TI  - Switching antipsychotics to aripiprazole or blonanserin and plasma monoamine
      metabolites levels in patients with schizophrenia.
AB  - OBJECTIVE: Blonanserin is a novel atypical antipsychotic drug that has efficacy
      equal to risperidone. We investigated the effects of aripiprazole and blonanserin
      on clinical symptoms and plasma levels of homovanillic acid (pHVA) and 3-methoxy
      4hydroxyphenylglycol in the switching strategy of schizophrenia. METHODS: Twenty
      two Japanese patients with schizophrenia were enrolled into this open study. The
      antipsychotics of all patients were switched to aripiprazole or blonanserin for
      the improvement of clinical symptoms or side effects. Plasma monoamine
      metabolites levels were analyzed with high-performance liquid chromatography.
      RESULTS: There were no significant effects for time (p = 0.346) or time * group
      interaction (p = 0.27) on the changes of positive and negative syndrome scale
      (PANSS) total score, although blonanserin decreased PANSS scores. We observed
      negative correlation between pHVA at baseline and the change in PANSS total score
      (rs = -0.450, p = 0.046). We also found positive correlation between the changes
      in pHVA and the changes in PANSS total (rs = 0.536, p = 0.015) and positive (rs =
      0.572, p = 0.008) scores. CONCLUSIONS: There were no differences between
      blonanserin and aripiprazole in the improvement of clinical symptoms. Our results
      suggest that pHVA may be useful indicator for the switching strategy to
      aripiprazole or blonanserin in schizophrenia.

PMID- 24590546
TI  - Pharmacokinetics and tolerability of paliperidone palmitate injection in Chinese
      subjects.
AB  - OBJECTIVE: The objective of this study was to characterize the pharmacokinetics
      of 25, 100, and 150 mg equivalents (eq.) of paliperidone long-acting injection in
      Chinese subjects with schizophrenia. METHODS: This was an open-label, randomized,
      parallel group, multicenter study. A total of 48 patients were randomized in a
      1:1:1 ratio to one of three groups. Sequential blood samples were collected
      immediately before injection on day 1 and up to 210 days after the first
      injection. The plasma paliperidone concentrations were determined by a validated
      high-performance liquid chromatography/tandem mass spectrometry method. RESULTS:
      A total of 47 patients received at least one injection of the study medication,
      and 43 completed the study. The pharmacokinetic (PK) parameters, such as time to
      maximum concentration, t1/2, and CL/F, were comparable across the three treatment
      groups (p = 0.935, 0.349, and 0.794, respectively). The differences in maximum
      plasma concentration, AUC (035 days), AUC (0-210 days), and AUC (0-infinity) were
      significant (p < 0.001) and dose proportional. The inter-individual variation of
      PK parameters was large. The most frequent treatment-emergent adverse events were
      prolactin level increasing, injection site pain, tremor, dry mouth, and
      constipation. CONCLUSIONS: The pharmacokinetics of paliperidone palmitate are
      linear with respect to time in Chinese subjects with schizophrenia at injections
      from 25 to 150 mg eq.

PMID- 24590549
TI  - Using activity theory to study cultural complexity in medical education.
AB  - There is a growing need for research on culture, cultural differences and
      cultural effects of globalization in medical education, but these are complex
      phenomena to investigate. Socio-cultural activity theory seems a useful framework
      to study cultural complexity, because it matches current views on culture as a
      dynamic process situated in a social context, and has been valued in diverse
      fields for yielding rich understandings of complex issues and key factors
      involved. This paper explains how activity theory can be used in (cross-)cultural
      medical education research. We discuss activity theory's theoretical background
      and principles, and we show how these can be applied to the cultural research
      practice by discussing the steps involved in a cross-cultural study that we
      conducted, from formulating research questions to drawing conclusions. We
      describe how the activity system, the unit of analysis in activity theory, can
      serve as an organizing principle to grasp cultural complexity. We end with
      reflections on the theoretical and practical use of activity theory for cultural
      research and note that it is not a shortcut to capture cultural complexity: it is
      a challenge for researchers to determine the boundaries of their study and to
      analyze and interpret the dynamics of the activity system. 

PMID- 24590548
TI  - Eudragit L/HPMCAS blend enteric-coated lansoprazole pellets: enhanced drug
      stability and oral bioavailability.
AB  - The objectives of the present work were to use blends of Eudragit L and
      hydroxypropyl methylcellulose acetate succinate (HPMCAS) as enteric film coatings
      for lansoprazole (LSP) pellets. The enteric-coated pellets were prepared with a
      fluid-bed coater. The influence of the blend ratio, type of plasticizer,
      plasticizer level, coating level, and curing conditions on gastric stability in
      vitro drug release and drug stability was evaluated. Furthermore, the
      bioavailability of the blend-coated pellets in beagle dogs was also performed.
      The blend-coated pellets exhibited significant improvement of gastric stability
      and drug stability compared to the pure polymer-coated pellets. Moreover, the AUC
      values of blend-coated pellets were greater than that of the pure polymer-coated
      pellets. It was concluded that the using blends of Eudragit L and HPMCAS as
      enteric film coatings for LSP pellets improved the drug stability and oral
      bioavailability.

PMID- 24590550
TI  - Hepatic fat during fasting and refeeding by MRI fat quantification.
AB  - PURPOSE: To explore the sensitivity of high-field small animal magnetic resonance
      imaging to dynamic changes in fat content in the liver and to characterize the
      effect of prandial state on imaging studies of hepatic fat. MATERIALS AND
      METHODS: A total of three timepoints were acquired using asymmetric spin-echo
      acquisitions for 12 mice with 24-hour spacing. After the first scan, half of the
      cohort was placed on a water-only diet. The second half of the cohort continued
      to have access to their high-fat chow. The scans were repeated after 24 hours.
      All animals were then returned to the high-fat diet, and the scans were again
      repeated after 24 hours. Fat fraction maps were computed using previously
      described methods. Regions of interests were manually drawn in the livers and the
      patterns of the two groups over time were compared. RESULTS: Five out of six of
      the animals in the starved group showed an increase in hepatic fat fraction
      during the fasting period (average increase 0.54 +/- 0.48), which decreased on
      refeeding. Analysis of variance indicated that the results significantly depended
      on both the group and the timepoint (P = 0.003). CONCLUSION: Fat-water imaging
      methods are able to measure hepatic fat changes caused by short-term dietary
      perturbations.

PMID- 24590551
TI  - Fostering self-endorsed motivation to change in patients with an eating disorder:
      the role of perceived autonomy support and psychological need satisfaction.
AB  - OBJECTIVE: Although several studies have established the beneficial effects of
      self-endorsed forms of motivation for lasting therapeutic change, the way
      patients with an eating disorder can be encouraged to volitionally pursue change
      has received less attention. On the basis of Self-Determination Theory, this
      longitudinal study addressed the role of an autonomy-supportive environment and
      psychological need satisfaction in fostering self-endorsed motivation for change
      and subsequent weight gain. METHOD: Female inpatients (n = 84) with mainly
      anorexia nervosa and bulimia nervosa filled out questionnaires at the onset of,
      during, and at the end of treatment regarding their perceived autonomy support
      from parents, staff members, and fellow patients, their psychological need
      satisfaction, and their reasons for undertaking change. Furthermore, the body
      mass index (BMI) of the patients at the onset and end of treatment was assessed
      by the staff. Path analyses were used to investigate the relations between these
      constructs. RESULTS: At the start of treatment, perceived parental autonomy
      support related positively to self-endorsed motivation through psychological need
      satisfaction. Perceived staff and fellow patients autonomy support related to
      changes in self-endorsed motivation over the course of treatment through
      fostering change in psychological need satisfaction. Finally, relative increases
      in self-endorsed motivation related to relative increases in BMI throughout
      treatment in a subgroup of patients with anorexia nervosa. DISCUSSION: These
      results point to the importance of an autonomy-supportive context for
      facilitating self-endorsed motivation.

PMID- 24590553
TI  - Cytochrome P450 catalyzed oxidative hydroxylation of achiral organic compounds
      with simultaneous creation of two chirality centers in a single C-H activation
      step.
AB  - Regio- and stereoselective oxidative hydroxylation of achiral or chiral organic
      compounds mediated by synthetic reagents, catalysts, or enzymes generally leads
      to the formation of one new chiral center that appears in the respective
      enantiomeric or diastereomeric alcohols. By contrast, when subjecting appropriate
      achiral compounds to this type of C-H activation, the simultaneous creation of
      two chiral centers with a defined relative and absolute configuration may result,
      provided that control of the regio-, diastereo-, and enantioselectivity is
      ensured. The present study demonstrates that such control is possible by using
      wild type or mutant forms of the monooxygenase cytochrome P450 BM3 as catalysts
      in the oxidative hydroxylation of methylcyclohexane and seven other
      monosubstituted cyclohexane derivatives.

PMID- 24590554
TI  - Optimising deep anterior lamellar keratoplasty  (DALK) using intraoperative
      online optical coherence  tomography (iOCT).
AB  - BACKGROUND/AIMS: To describe the use of intraoperative online optical coherence
      tomography (iOCT) for improving deep anterior lamellar keratoplasty (DALK)
      surgery. METHODS: Retrospective case series of 6 eyes of 6 male patients with
      keratokonus, corneal dystrophy or herpetic stromal scars undergoing DALK were
      investigated using intraoperative optical coherence tomography and postsurgical
      image/video analysis. Main outcome measures were: visibility of surgical steps,
      especially, assessment of placement depth of injection needle, preparation of
      bare Descemet's membrane and drainage of interface fluid. RESULTS: iOCT enables
      real-time visualisation of all surgical steps of DALK procedure in all patients.
      Placement of air injection needle above Descemet's membrane was reliably
      monitored as was presence of bare Descemet's membrane and potential interface
      fluid. CONCLUSIONS: iOCT assists with visualisation of injection needle placement
      and with assessment of bare Descemet's membrane as well as interface fluid during
      the DALK procedure. Overall iOCT may be a helpful device that supports surgeons
      in all steps of DALK procedure.

PMID- 24590555
TI  - Prevalence and causes of vision loss in North Africa and the Middle East: 1990
      2010.
AB  - BACKGROUND: To describe the prevalence and causes of visual impairment and
      blindness in North Africa and the Middle East (NAME) in 1990 and 2010. METHODS:
      Based on a systematic review of medical literature, we examined prevalence and
      causes of moderate and severe vision impairment (MSVI; presenting visual acuity
      <6/18, >=3/60) and blindness (presenting visual acuity <3/60). RESULTS: In NAME,
      the age-standardised prevalence of blindness decreased from 2.1% to 1.1% and MSVI
      from 7.1% to 4.5%. In 2010, 3.119 million people were blind, and 13.700 million
      had MSVI. Women were generally more often affected than men. Main causes of
      blindness were cataract, uncorrected refractive error, macular degeneration and
      glaucoma. Main causes of MSVI were cataract and uncorrected refractive errors.
      Proportions of blindness and MSVI from trachoma significantly decreased.
      CONCLUSIONS: Although the absolute numbers of people with blindness and MSVI
      increased from 1990 to 2010, the overall age-standardised prevalence of blindness
      and MSVI among all ages and among those aged 50 years and older decreased
      significantly (p<0.05). Cataract and uncorrected refractive error were the major
      causes of blindness and MSVI.

PMID- 24590556
TI  - Ophthalmic statistics note 2: absence of evidence is not evidence of absence.

PMID- 24590557
TI  - Keratoprostheses: are we there yet?

PMID- 24590558
TI  - Characterisation of Schlemm's canal cross-sectional area.
AB  - PURPOSE: To compare three methods of Schlemm's canal (SC) cross-sectional area
      (CSA) measurement. METHODS: Ten eyes (10 healthy volunteers) were imaged three
      times using spectral-domain optical coherence tomography (Cirrus HD-OCT, Zeiss,
      Dublin, California, USA). Aqueous outflow vascular structures and SC collector
      channel ostia were used as landmarks to identify a reference location within the
      limbus. SC CSA was assessed within a 1 mm segment (+/-15 frames of the reference,
      31 frames in all) by three techniques. (1) Using a random number table, SC CSA in
      five random frames from the set of 31 surrounding the reference were measured and
      averaged. (2) The most easily visualised SC location (subjective) was measured,
      and (3) SC CSA was measured in all 31 consecutive B-scans, and averaged.
      (comprehensive average, gold standard). Subjective and random CSAs were compared
      with the comprehensive by general estimating equation modelling, and structural
      equation modelling quantified agreement. RESULTS: The average from five random
      locations (4175+/-1045 um(2)) was not significantly different than that obtained
      from the gold standard comprehensive assessment (4064+/-1308 um(2), p=0.6537).
      Subjectively located SC CSA (7614+/-2162 um(2)) was significantly larger than the
      comprehensive gold standard SC CSA (p<0.0001). The average of five random frames
      produced significantly less bias than did subjective location, yielding a
      calibration line crossing the 'no-bias' line. DISCUSSION: Subjectively located SC
      CSA measurements produce high estimates of SC CSA. SC assessed by measuring five
      random locations estimate CSA was similar to the gold standard estimate.

PMID- 24590559
TI  - Roseomonas alkaliterrae sp. nov., isolated from an alkali geothermal soil sample
      in Tengchong, Yunnan, South-West China.
AB  - An alkalitolerant, thermotolerant and Gram-stain negative bacterium, designated
      strain YIM 78007(T), was isolated from an alkaline geothermal soil sample from
      Hehua hot spring, Tengchong, Yunnan province, south-west China. Cells of strain
      YIM 78007(T) were observed to be aerobic and short rod-shaped. The colonies were
      observed to be orange-red, convex and circular. 16S rRNA gene sequence-based
      phylogenetic analysis showed that strain YIM 78007(T) clustered with members of
      the genus Roseomonas (with similarities from 97.2 to 92.2 %). Optimal growth of
      strain YIM 78007 occurs at 40-50  degrees C and pH 8.0-10.0. The predominant
      ubiquinone was identified as Q-10 and the major fatty acids were identified as
      C18:1 omega7c and C16:0. The polar lipids were identified as
      diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine, two
      unidentified aminolipids and one unknown phospholipid. The G + C content of the
      genomic DNA was determined to be 63 mol %. The levels of DNA-DNA hybridization
      relatedness between strain YIM 78007(T) and its closet neighbours (Roseomonas
      lacus JCM 13283(T) and Roseomonas terrae JCM 14592(T)) were well below the
      threshold required for the proposal of a novel species. The results of
      physiological and biochemical characteristics, the phylogenetic analysis, as well
      as low DNA-DNA hybridization values, allowed the phenotypic and genotypic
      differentiation of strain YIM 78007(T) from its closest phylogenetic neighbours.
      Therefore, strain YIM 78007(T) is considered to represent a novel species of the
      genus Roseomonas, for which the name Roseomonas alkaliterrae sp. nov. is
      proposed. The type strain is YIM 78007(T) (=BCRC 80644(T) = JCM 19656(T)). 

PMID- 24590561
TI  - Symptom perception in healthy menopausal women: Can we predict concordance
      between subjective and physiological measures of vasomotor symptoms?
AB  - OBJECTIVES: Perception of physical symptoms is an important factor in medical
      help-seeking. We aimed to examine both physiological and subjective measures of a
      commonly reported physical symptom-vasomotor symptoms (hot flushes and night
      sweats; HF/NS), and to investigate factors that might influence symptom
      perception, that is, concordance, over-reporting, and under-reporting of symptoms
      in healthy menopausal women. METHODS: One hundred and forty women completed
      questionnaires assessing depressed mood, anxiety, stress, somatic symptoms,
      beliefs about HF/NS, and somatic amplification. Subjective and objective (24-h
      sternal skin conductance) measurements of HF/NS were obtained to assess
      concordance. RESULTS: Thirty-seven percent of HF/NS were concordant while 47 and
      16 % were under-reported and over-reported, respectively. Depressed mood,
      anxiety, somatic symptoms, and negative beliefs about HF/NS were associated with
      (higher) concordance, (less) under-, or (more) over-reporting. Negative beliefs
      about night sweats and sleep were the strongest predictors of concordance,
      whereas additional somatic symptoms and smoking predicted over-reporting.
      CONCLUSIONS: Just over one third of physiologically recorded HF/NS were perceived
      as hot flushes; under-reporting of symptoms was more common than over-reporting.
      Interestingly, women who were more accurate in detecting physiological HF/NS
      tended to report more psychological and somatic symptoms and negative beliefs
      about HF/NS. Both measures should be included as outcomes of clinical trials.

PMID- 24590560
TI  - Silica nanowire arrays for diffraction-based bioaffinity sensing.
AB  - Arrays of electrodeposited silica nanowires (SiO2 NWs) have been fabricated over
      large areas (cm(2)) on fluoropolymer thin films attached to glass substrates by a
      combination of photolithography and electrochemically triggered sol-gel nanoscale
      deposition. Optical and scanning electron microscopy (SEM) measurements revealed
      that the SiO2 NW arrays had an average spacing of ten micrometers and an average
      width of 700 nm with a significant grain structure that was a result of the sol
      gel deposition process. The optical diffraction properties at 633 nm of the SiO2
      NW arrays were characterized when placed in contact with solutions by using a
      prism-coupled total internal reflection geometry; quantification of changes in
      these diffraction properties was applied in various sensing applications. Bulk
      refractive index sensing by using the SiO2 NW grating was demonstrated with a
      sensitivity of 1.30*10(-5) RIU. Toposelectively chemically modified SiO2 NW
      arrays were used for diffraction biosensing measurements of surface binding
      events, such as the electrostatic adsorption of gold nanoparticles and the
      bioaffinity adsorption of streptavidin onto a biotin monolayer. Finally, the
      application of the SiO2 NW arrays for practical medical-diagnostic applications
      was demonstrated by monitoring the diffraction of SiO2 NW arrays functionalized
      with a single-stranded (ss)DNA aptamer to detect human alpha-thrombin from
      solutions at sub-pathologic nanomolar concentrations.

PMID- 24590562
TI  - Memory versus perception of body size in patients with anorexia nervosa and
      healthy controls.
AB  - The objective of this study was to compare body size estimation based on memory
      versus perception, in patients with anorexia nervosa (AN) and healthy controls,
      adjusting for possible confounders. Seventy-one women (AN: 37, controls: 35),
      aged 14-29 years, were assessed with a computerized body size estimation morphing
      program. Information was gathered on depression, anxiety, time since last meal,
      weight and height. Results showed that patients overestimated their body size
      significantly more than controls, both in the memory and perception condition.
      Further, patients overestimated their body size significantly more when
      estimation was based on perception than memory. When controlling for anxiety, the
      difference between patients and controls no longer reached significance. None of
      the other confounders contributed significantly to the model. The results suggest
      that anxiety plays a role in overestimation of body size in AN. This finding
      might inform treatment, suggesting that more focus should be aimed at the
      underlying anxiety.

PMID- 24590563
TI  - Process evaluation of the maudsley model for treatment of adults with anorexia
      nervosa trial. Part II: Patient experiences of two psychological therapies for
      treatment of anorexia nervosa.
AB  - OBJECTIVE: This study is the second part of a process evaluation, embedded in the
      MOSAIC study, a large randomised controlled trial comparing two different
      psychological therapies, the Maudsley Model for Treatment of Adults with Anorexia
      Nervosa (MANTRA) and Specialist Supportive Clinical Management (SSCM). The study
      adopted a qualitative approach to examine patient experiences of the two
      treatments. METHOD: Seventeen semi-structured interviews were conducted with
      Anorexia Nervosa and Eating Disorder Not Otherwise Specified-Anorexia Nervosa
      type patients, and transcripts were analysed thematically. RESULTS: Patient
      responses yielded five main themes: positive and helpful aspects, beneficial
      outcomes, less helpful aspects, possible improvements to the treatments, and the
      therapeutic and external environment. The findings show clear differences and
      some overlaps between patients' views on MANTRA and SSCM. DISCUSSION: Both
      therapies were experienced by patients as credible and largely helpful, albeit in
      different ways. These results are in agreement with those of therapists' views on
      these treatments.

PMID- 24590564
TI  - Impact of metabolic syndrome on stress urinary incontinence in pre- and
      postmenopausal women.
AB  - AIM: In the present study, we prospectively collected data from pre- to
      postmenopausal women with or without metabolic syndrome (MetS) and evaluated the
      impact of MetS on stress urinary incontinence (SUI) in women. MATERIAL AND
      METHODS: The women divided into four equal groups: premenopausal with and without
      MetS; postmenopausal with and without MetS. There were 100 women in each group.
      We assessed the women for SUI at gynecologic position and we determined cough
      stress test. MetS was defined according to the criteria established in 2005 by
      the NCEP/ATP III. RESULTS: Mean age was 48.52 +/- 8.16 in women with MetS and
      48.81 +/- 8.31 in women without MetS. SUI was found more often in both pre- and
      postmenopausal women with MetS (p = 0.001 and p < 0.001). It seems that
      postmenopausal women have more SUI than premenopausal women with MetS. We also
      evaluated the association between five components of MetS and SUI. Just, higher
      fasting glucose levels and waist circumference were significantly associated with
      SUI (p < 0.05). CONCLUSION: Our study shows that SUI is more prevalent in pre-
      and postmenopausal women with the MetS. SUI can be prevented with lifestyle
      changes for MetS. Multicenter studies with larger series and molecular studies
      are needed to determine the impact of the MetS on SUI.

PMID- 24590565
TI  - Combined oral contraceptives: venous thrombosis.
AB  - BACKGROUND: Combined oral contraceptive (COC) use has been associated with venous
      thrombosis (VT) (i.e., deep venous thrombosis and pulmonary embolism). The VT
      risk has been evaluated for many estrogen doses and progestagen types contained
      in COC but no comprehensive comparison involving commonly used COC is available.
      OBJECTIVES: To provide a comprehensive overview of the risk of venous thrombosis
      in women using different combined oral contraceptives. SEARCH METHODS: Electronic
      databases (Pubmed, Embase, Web of Science, Cochrane, CINAHL, Academic Search
      Premier and ScienceDirect) were searched in 22 April 2013 for eligible studies,
      without language restrictions. SELECTION CRITERIA: We selected studies including
      healthy women taking COC with VT as outcome. DATA COLLECTION AND ANALYSIS: The
      primary outcome of interest was a fatal or non-fatal first event of venous
      thrombosis with the main focus on deep venous thrombosis or pulmonary embolism.
      Publications with at least 10 events in total were eligible. The network meta
      analysis was performed using an extension of frequentist random effects models
      for mixed multiple treatment comparisons. Unadjusted relative risks with 95%
      confidence intervals were reported.Two independent reviewers extracted data from
      selected studies. MAIN RESULTS: 3110 publications were retrieved through a search
      strategy; 25 publications reporting on 26 studies were included. Incidence of
      venous thrombosis in non-users from two included cohorts was 0.19 and 0.37 per 1
      000 person years, in line with previously reported incidences of 0,16 per 1 000
      person years. Use of combined oral contraceptives increased the risk of venous
      thrombosis compared with non-use (relative risk 3.5, 95% confidence interval 2.9
      to 4.3). The relative risk of venous thrombosis for combined oral contraceptives
      with 30-35 MUg ethinylestradiol and gestodene, desogestrel, cyproterone acetate,
      or drospirenone were similar and about 50-80% higher than for combined oral
      contraceptives with levonorgestrel. A dose related effect of ethinylestradiol was
      observed for gestodene, desogestrel, and levonorgestrel, with higher doses being
      associated with higher thrombosis risk. AUTHORS' CONCLUSIONS: All combined oral
      contraceptives investigated in this analysis were associated with an increased
      risk of venous thrombosis. The effect size depended both on the progestogen used
      and the dose of ethinylestradiol. Risk of venous thrombosis for combined oral
      contraceptives with 30-35 MUg ethinylestradiol and gestodene, desogestrel,
      cyproterone acetate and drospirenone were similar, and about 50-80% higher than
      with levonorgestrel. The combined oral contraceptive with the lowest possible
      dose of ethinylestradiol and good compliance should be prescribed-that is, 30 MUg
      ethinylestradiol with levonorgestrel.

PMID- 24590566
TI  - Rhodiola inhibits dengue virus multiplication by inducing innate immune response
      genes RIG-I, MDA5 and ISG in human monocytes.
AB  - Recognition of virus infection by retinoic acid-inducible gene (RIG) I and
      melanoma differentiation-associated protein (MDA) 5, which are RNA helicases, and
      interferon-stimulated gene (ISG) 15 activates cascades of signal transduction
      pathways leading to production of type I interferons and proinflammatory
      cytokines that orchestrate the elimination of the viruses. However, it has been
      demonstrated that RNA-helicase-mediated innate immunity plays an essential role
      in defending the host from infection. In our efforts to identify plant-derived
      antivirals that selectively enhance ISG- and RNA-helicase-mediated antiviral
      immune responses, we identified a plant, rhodiola, that significantly promoted
      ISG, RIG-I and MDA 5 gene expression and an antiviral immune response against
      dengue virus (DENV) infection. Rhodiola induced interferon (IFN) beta and other
      cytokines, including IL-1beta, TNF-alpha, IL-6 and IL-8, in infected cells. It
      was also found that rhodiola upregulated phosphorylated eIF-2alpha, PKR and NF-kB
      in infected cells. In addition, the number of NK cells was also increased by
      rhodiola treatment in dengue-virus-infected human PBMCs. Treatment with a crude
      extract of rhodiola (RAE) resulted in effects in the 20 % range, which is similar
      to the magnitude of the same effects observed in DENV infections. Taken together,
      our results imply that rhodiola induces pharmacological modulation of RIG-I, MDA
      5 and ISG signal transduction pathways in favor of the induction of a beneficial
      antiviral immune response against dengue virus, which can be a novel therapeutic
      strategy for management of infection.

PMID- 24590567
TI  - Development and evaluation of a recombinant-glycoprotein-based latex
      agglutination test for rabies virus antibody assessment.
AB  - The measurement of neutralizing antibodies induced by the glycoprotein of rabies
      virus is indispensable for assessing the level of neutralizing antibodies in
      animals or humans. A rapid fluorescent focus inhibition test (RFFIT) has been
      approved by WHO and is the most widely used method to measure the virus
      neutralizing antibody content in serum, but a rapid test system would be of great
      value to screen large numbers of serum samples. To develop and evaluate a latex
      agglutination test (LAT) for measuring rabies virus antibodies, a recombinant
      glycoprotein was expressed in an insect cell system and purified, and the protein
      was coated onto latex beads at concentrations of 0.1, 0.25, 0.5, 0.75, and 1
      mg/ml to find out the optimal concentration for coating latex beads. It was found
      that 0.5 mg/ml of recombinant protein was optimal for coating latex beads, and
      this concentration was used to sensitize the latex beads for screening of dog
      serum samples. Grading of LAT results was done with standard reference serum with
      known antibody titers. A total of 228 serum samples were tested, out of which 145
      samples were positive by both RFFIT and LAT, and the specificity was found to be
      100 %. In RFFIT, 151 samples were positive, the sensitivity was found to be 96.03
      %, and the accuracy/concordance was found to be 97.39 %. A rapid field test-a
      latex agglutination test (LAT)-was developed and evaluated for rabies virus
      antibody assessment using recombinant glycoprotein of rabies virus expressed in
      an insect cell system.

PMID- 24590568
TI  - Validation of the 4AT, a new instrument for rapid delirium screening: a study in
      234 hospitalised older people.
AB  - OBJECTIVE: to evaluate the performance of the 4 'A's Test (4AT) in screening for
      delirium in older patients. The 4AT is a new test for rapid screening of delirium
      in routine clinical practice. DESIGN: : prospective study of consecutively
      admitted elderly patients with independent 4AT and reference standard
      assessments. SETTING: : an acute geriatrics ward and a department of
      rehabilitation. PARTICIPANTS: two hundred and thirty-six patients (aged >=70
      years) consecutively admitted over a period of 4 months. MEASUREMENTS: in each
      centre, the 4AT was administered by a geriatrician to eligible patients within 24
      h of admission. Reference standard delirium diagnosis (DSM-IV-TR criteria) was
      obtained within 30 min by a different geriatrician who was blind to the 4AT
      score. The presence of dementia was assessed using the Alzheimer's Questionnaire
      and the informant section of the Clinical Dementia Rating scale. The main outcome
      measure was the accuracy of the 4AT in diagnosing delirium. RESULTS: patients
      were 83.9 +/- 6.1 years old, and the majority were women (64%). Delirium was
      detected in 12.3% (n = 29), dementia in 31.2% (n = 74) and a combination of both
      in 7.2% (n = 17). The 4AT had a sensitivity of 89.7% and specificity 84.1% for
      delirium. The areas under the receiver operating characteristic curves for
      delirium diagnosis were 0.93 in the whole population, 0.92 in patients without
      dementia and 0.89 in patients with dementia. CONCLUSIONS: the 4AT is a sensitive
      and specific method of screening for delirium in hospitalised older people. Its
      brevity and simplicity support its use in routine clinical practice.

PMID- 24590569
TI  - Aminoglycosides use in patients over 75 years old.
AB  - OBJECTIVE: to describe aminoglycoside use and nephrotoxicity in patients older
      than 75 years. DESIGN: retrospective multicenter study. SETTING: hospital
      department, rehabilitation, long-term care center. POPULATION: patients >=75
      years old treated by aminoglycosides. RESULTS: 184 patients, mean age: 84.4 years
      (range: 75-101). One hundred and twenty-seven patients received other nephrotoxic
      drug(s). Gentamicin (70%) and amikacin (30%) were used and the once-daily dosing
      was preferred (92%). Average treatment period was 2.75 (1-10) days for amikacin
      and 4.4 (1-30) for gentamicin with average dosage 13.5 and 3.5 mg/kg/day,
      respectively. The monitoring of maximal plasmatic concentration (Cmax) was done
      in 37 patients, 9 of them had probabilistic treatment. Only one had a Cmax
      fulfilling the objective of French recommendations (gentamicin >30 mg/l, amikacin
      >60 mg/l). When infection was documented, the objective of Cmax >10 * minimal
      inhibitory concentration of the strain was reached for 27%. Minimal plasmatic
      concentration was checked in 38% of cases, with adequate value (gentamicin <0.5
      mg/l, amikacin <2.5 mg/l) for 37%. At the end of aminoglycoside course, 40
      patients increased their serum creatinine >25% of the baseline value. In
      multivariate analysis, this was associated with treatment length >=3 days and
      concomitant use of nephrotoxic drugs. CONCLUSION: aminoglycosides dosing used in
      elderly patients probably need therapeutic drug monitoring and dose adjustment.
      Aminoglycosides are used to treat severe infections. One of the most important
      side effects is nephrotoxicity in oldest patients. To minimise nephrotoxicity,
      short treatments are necessary and avoiding others nephrotoxic drugs could be
      relevant.

PMID- 24590570
TI  - Altered hematopoietic stem cell and osteoclast precursor frequency in cathepsin K
      null mice.
AB  - Cathepsin K (CatK) is a lysosomal cysteine protease necessary for bone resorption
      by osteoclasts (OCs), which originate from myeloid hematopoietic precursors. CatK
      deficient (CatK(-/-) ) mice show osteopetrosis due to defective resorption by
      OCs, which are increased in number in these mice. We investigated whether genetic
      ablation of CatK altered the number of hematopoietic stem cells (HSCs) and OC
      precursor cells (OCPs) using two mouse models: CatK(-/-) mice and a knock-in
      mouse model in which the CatK gene (ctsk) is replaced by cre recombinase. We
      found that CatK deletion in mice significantly increased the number of HSCs in
      the spleen and decreased their number in bone marrow. In contrast, the number of
      early OCPs was unchanged in the bone marrow. However, the number of committed
      CD11b(+) OCPs was increased in the bone marrow of CatK(-/-) compared to wild-type
      (WT) mice. In addition, the percentage but not the number of OCPs was decreased
      in the spleen of CatK(-/-) mice relative to WT. To understand whether increased
      commitment to OC lineage in CatK(-/-) mice is influenced by the bone marrow
      microenvironment, CatK(Cre/+) or CatK(Cre/Cre) red fluorescently labeled OCPs
      were injected into WT mice, which were also subjected to a mid-diaphyseal femoral
      fracture. The number of OCs derived from the intravenously injected CatK(Cre/Cre)
      OCPs was lower in the fracture callus compared to mice injected with CatK(+/Cre)
      OCPs. Hence, in addition to its other effects, the absence of CatK in OCP limits
      their ability to engraft in a repairing fracture callus compared to WT OCP.

PMID- 24590571
TI  - Electrostatic and non-covalent interactions in dicationic imidazolium-sulfonium
      salts with mixed anions.
AB  - A series of thioether-functionalised imidazolium salts have been prepared and
      characterized. Subsequent reaction of the thioether-functionalised imidazolium
      salts with iodomethane affords imidazolium-sulfonium salts composed of doubly
      charged cations and two different anions. Imidazolium-sulfonium salts containing
      a single anion type are obtained either by a solvent extraction method or by
      anion exchange. The imidazolium-sulfonium salts undergo a methyl-transfer
      reaction on exposure to water, giving rise to a new, singly charged imidazolium
      salt with iodide introduced at the 2-position of the imidazolium ring. Crystal
      structures of some of the imidazolium-sulfonium salts were determined by X-ray
      crystallography providing the topology of the interactions between the dications
      and the anions. Electrospray ionization mass spectrometry and quantum-chemical
      calculations were used to rationalise the relative strength of these
      interactions. 

PMID- 24590572
TI  - The Rietveld method as a tool to quantify the amorphous amount of
      microcrystalline cellulose.
AB  - With the use of X-ray powder diffraction data and the Rietveld method, we
      verified that both microcrystalline cellulose PH-101 and PH-102 presented
      differences in the crystallinity degree. The results revealed these samples are
      semicrystalline in nature and via Rietveld refinements, it was possible, adding a
      known amount of an internal standard of corundum to the samples, to perform
      quantitative phase analyses, which allowed us to determine the amorphous amount
      of the studied samples: 63.7(11) wt % in microcrystalline cellulose PH-101 and
      51.0(11) wt % in microcrystalline cellulose PH-102. An important contribution of
      this work refers to the attempt of using this simple method, permitting to
      evaluate the degree of crystallinity of microcrystalline cellulose.

PMID- 24590573
TI  - Epidemic dynamics and host immune response: a nested approach.
AB  - This paper proposes an approach for building epidemiological models that
      incorporate the intra-host pathogen-immunity dynamics. The infected population is
      structured in terms of pathogen load and level of immunity, and the initial
      infection load may depend on the load of the individual from whom the infection
      is acquired. In particular, we focus on the case in which the initial inoculum is
      taken proportional to the load of the infectant. Possible reinfections are
      disregarded. Such an approach is applied to formulate an epidemic model with
      isolation in a closed population by introducing a specific intra-host dynamics. A
      numerical scheme for the solution of model equations is developed, and some
      numerical results illustrating the role of the initial inoculum, of the isolation
      threshold and of the pathogen dynamics on the epidemic evolution are presented.
      From the simulations the distributions of latency, infectivity, and isolation
      times can be also derived; however the predictions of the present models differ
      qualitatively from those of traditional SEIHR models with distributed latency,
      infectivity and isolation periods. 

PMID- 24590574
TI  - Exact deterministic representation of Markovian SIR epidemics on networks with
      and without loops.
AB  - In a previous paper Sharkey et al. (Bull Math Biol doi: 10.1007/s11538-013-9923-5
      , 2012) proved the exactness of closures at the level of triples for Markovian
      [Formula: see text] (susceptible-infected-removed) dynamics on tree-like
      networks. This resulted in a deterministic representation of the epidemic
      dynamics on the network that can be numerically evaluated. In this paper, we
      extend this modelling framework to certain classes of networks exhibiting loops.
      We show that closures where the loops are kept intact are exact, and lead to a
      simplified and numerically solvable system of ODEs (ordinary-differential
      equations). The findings of the paper lead us to a generalisation of closures
      that are based on partitioning the network around nodes that are cut-vertices
      (i.e. the removal of such a node leads to the network breaking down into at least
      two disjointed components or subnetworks). Exploiting this structural property of
      the network yields some natural closures, where the evolution of a particular
      state can typically be exactly given in terms of the corresponding or projected
      states on the subnetworks and the cut-vertex. A byproduct of this analysis is an
      alternative probabilistic proof of the exactness of the closures for tree-like
      networks presented in Sharkey et al. (Bull Math Biol doi: 10.1007/s11538-013-9923
      5 , 2012). In this paper we also elaborate on how the main result can be applied
      to more realistic networks, for which we write down the ODEs explicitly and
      compare output from these to results from simulation. Furthermore, we give a
      general, recipe-like method of how to apply the reduction by closures technique
      for arbitrary networks, and give an upper bound on the maximum number of
      equations needed for an exact representation. 

PMID- 24590575
TI  - Safety analysis of Epzicom(r) (lamivudine/abacavir sulfate) in post-marketing
      surveillance in Japan.
AB  - PURPOSE: To obtain safety and effectiveness data on a combined anti-HIV drug,
      Epzicom (abacavir 600 mg/lamivudine 300 mg), a post-marketing surveillance on
      Epzicom that was required by the Japanese regulatory authority was conducted
      between January 2005 and December 2010. METHODS: A joint survey (HIV-related drug
      [HRD] survey) has been conducted involving manufacturers of drugs for treatment
      of HIV infection in Japan. Safety and effectiveness data from total 624 cases
      (1107.3 person-years) registered to the HRD surveys and received Epzicom were
      obtained. Adverse drug reactions (ADRs) were defined as adverse events (AE) of
      which association with Epzicom could not be 'ruled out'. RESULTS: It was found
      that the incidence of ADR was 32.4% (202/624 cases) on the case basis. In
      addition, the frequently reported ADR included hyperlipidaemia (59 cases),
      hypertriglyceridaemia (21 cases), blood bilirubin increased (19 cases), gamma
      glutamyltransferase increase (14 cases), blood triglyceride increase (14 cases)
      and rash (14 cases). Serious AEs were seen in 19 patients (30 events), including
      one death (no evident association with Epzicom). There were four cases (0.6%) of
      survey-defined 'hypersensitivity', and the incidence was 0.9% (4/445) among
      abacavir naive patients; none of which was reported as serious. No case of
      myocardial infarction was reported. One pregnant case who delivered a normal baby
      by caesarean section was reported to have experienced aggravation of anaemia and
      nausea. CONCLUSIONS: The post-marketing surveillance indicated that the incidence
      of both ischaemic heart disease and hypersensitivity associated with Epzicom was
      considerably low, suggesting that this drug can be safely used in the Japanese
      population.

PMID- 24590576
TI  - Towards true carbaporphyrinoids: synthesis of 21-carba-23-thiaporphyrin.
AB  - In the search for porphyrinoids with a built-in cyclopentadienyl moiety (true
      carbaporphyrins), a rational synthesis of carbathiaporphyrin, the synthons, has
      been elaborated. The donors (C,N,S,N) in the porphyrinic core of
      carbathiaporphyrinoids are potentially of fundamental importance for generating
      organometallic complexes, as exemplified through formation of the palladium(II)
      complex. 

PMID- 24590578
TI  - Photoinduced electron transfer reactions of ruthenium(II)-complexes containing
      amino acid with quinones.
AB  - With the aim of mimicking, at basic level the photoinduced electron transfer
      process in the reaction center of photosystem II, ruthenium(II)-polypyridyl
      complexes, carrying amino acids were synthesized and studied their photoinduced
      electron transfer reactions with quinones by steady state and time resolved
      measurements. The reaction of quinones with excited state of ruthenium(II)
      complexes, I-V in acetonitrile has been studied by luminescence quenching
      technique and the rate constant, k(q), values are close to the diffusion
      controlled rate. The detection of the semiquinone anion radical in this system
      using time-resolved transient absorption spectroscopy confirms the electron
      transfer nature of the reaction. The semiclassical theory of electron transfer
      has been successfully applied to the photoluminescence quenching of Ru(II)
      complexes with quinones.

PMID- 24590577
TI  - M1 muscarinic acetylcholine receptor in Alzheimer's disease.
AB  - The degeneration of cholinergic neurons and cholinergic hypofunction are
      pathologies associated with Alzheimer's disease (AD). Muscarinic acetylcholine
      receptors (mAChRs) mediate acetylcholine-induced neurotransmission and five mAChR
      subtypes (M1-M5) have been identified. Among them, M1 mAChR is widely expressed
      in the central nervous system and has been implicated in many physiological and
      pathological brain functions. In addition, M1 mAChR is postulated to be an
      important therapeutic target for AD and several other neurodegenerative diseases.
      In this article, we review recent progress in understanding the functional
      involvement of M1 mAChR in AD pathology and in developing M1 mAChR agonists for
      AD treatment.

PMID- 24590579
TI  - Direct effects of morphine but not of fentanyl-type opioids on human 5-HT3A
      receptors in outside-out patch-clamp studies.
AB  - BACKGROUND: The alkaloid morphine is historically the oldest opiate, yet still
      today it has clinically important uses in analgesic therapies. The main analgesic
      effect of opioids, including synthetic opioids belonging to the family of 4
      anilidopiperidines, is mediated via activation of opioid receptors spread
      throughout the peripheral and central nervous system. However, morphine acting as
      a 'dirty' drug also exhibits effects on other receptor systems, e.g., the
      serotonergic system and its 5-HT3 receptor. Therefore, this study focuses on the
      interaction of morphine and fentanyl-type opioids (alfentanil, remifentanil and
      sufentanil) with 5-HT3A receptors. METHODS: Excised outside-out patches from
      human embryonic kidney-293 cells, stably transfected with the human 5-HT3A
      receptor cDNA, were used to determine the opioid effects using the patch-clamp
      technique. RESULTS: Within clinical concentrations, the effects of morphine are
      concentration-dependent. Morphine reduced current amplitudes, as well as
      activation and decay time constants. These effects were not competitive. Contrary
      to these results, all fentanyl-type opioids only exerted effects far above their
      clinical concentration ranges. These effects were not homogenous but varying.
      CONCLUSIONS: Morphine is an opioid compound exhibiting special antagonistic
      interaction with 5-HT3A receptors. This interaction is not shared by the newer
      synthetic derivatives of the fentanyl-type opioids in the clinical relevant
      concentration range.

PMID- 24590580
TI  - Antihypertensive efficacy of triple combination perindopril/indapamide plus
      amlodipine in high-risk hypertensives: results of the PIANIST study (Perindopril
      Indapamide plus AmlodipiNe in high rISk hyperTensive patients).
AB  - OBJECTIVE: Our objective was to evaluate a triple-drug antihypertensive strategy
      for blood pressure control in patients with difficult-to-treat hypertension.
      DESIGN: The Perindopril-Indapamide plus AmlodipiNe in high rISk hyperTensive
      patients (PIANIST) trial was an observational, 4-month, open-label study.
      PATIENTS AND INTERVENTIONS: A total of 4,731 patients at high or very high
      cardiovascular risk with hypertension that was not properly controlled [ , and
      for [corrected] whom study treatment (fixed-dose perindopril 10 mg/indapamide 2.5
      mg + amlodipine 5 or 10 mg) was consistent with their existing therapeutic plan,
      were included. OUTCOMES: One-sample t tests and Chi-squared tests were performed
      to evaluate changes in blood pressure. RESULTS: Mean baseline office blood
      pressure (OBP) was 160.5 +/- 13.3/93.8 +/- 8.7 mmHg. After 4 months of therapy,
      OBP decreased by 28.3 +/- 13.5/13.8 +/- 9.4 to 132.2 +/- 8.6/80.0 +/- 6.6 mmHg (p
      < 0.0001). Blood pressure targets were reached by 72.0% of patients and by 81 and
      91% of patients previously treated with an angiotensin-converting enzyme
      inhibitor/hydrochlorothiazide or an angiotensin receptor
      blocker/hydrochlorothiazide, respectively. Changes in OBP were 18.7 +/- 8.3/9.7
      +/- 7.2 mmHg for grade 1 (n = 1,679), 30.4 +/- 10.1/14.7 +/- 8.6 mmHg for grade 2
      (n = 2,397), and 45.4 +/- 15.1/20.7 +/- 12.1 mmHg for grade 3 patients (n = 655;
      all p < 0.0001). In patients who underwent ambulatory blood pressure monitoring
      (n = 104), 24-h mean blood pressure decreased from 147.4 +/- 13.8/82.1 +/- 11.9
      to 122.6 +/- 9.1/72.8 +/- 7.4 mmHg (p < 0.0001). Ankle edema was infrequent (0.2%
      of patients). CONCLUSION: Triple combination perindopril/indapamide/amlodipine
      was effectively and safely administered to a large population of high- and very
      high-risk hypertensive patients who had not reached target OBP values with
      previous treatment.

PMID- 24590582
TI  - Kobuvirus (Aichivirus B) infection in Brazilian cattle herds.
AB  - There are few studies involving the detection of Aichivirus B in cattle herds
      worldwide, and this virus has never been diagnosed in South America. This study
      evaluated 222 diarrhoeic faecal samples from four Brazilian geographical regions
      (South, Southeast, Midwest, and North), collected between February 2010 to May
      2012. To evaluate the frequency of occurrence in different types of livestock,
      samples from beef (n = 105) and dairy (n = 117) cattle herds were evaluated. To
      determine the category of animals more susceptible to infection, the sampling
      included samples from calves (n = 182) and adults animals (n = 40). The 216 bp
      fragment of the Aichivirus RdRp gene was amplified by a RT-PCR assay in 18.2 %
      (40/222) of the samples evaluated in both beef and dairy cattle animals. The
      highest (P < 0.05) detection rate (20.9 %; 38/182) of the Aichivirus B was found
      in calves. The nucleotide sequencing analysis showed that the Brazilian
      Aichivirus B strains clustered in a distinct branch in the phylogenetic tree of
      the European and Asiatic strains. This is the first description of Aichivirus B
      infection in Brazilian cattle herds. 

PMID- 24590581
TI  - Serelaxin: a novel therapy for acute heart failure with a range of hemodynamic
      and non-hemodynamic actions.
AB  - Acute heart failure (AHF) is characterized by high morbidity and mortality and
      high costs. Although the treatment of AHF has not changed substantially in recent
      decades, it is becoming clear that treatment strategies for AHF need to address
      both the immediate hemodynamic abnormalities giving rise to congestion as well as
      prevent organ damage that can influence long-term prognosis. Serelaxin, the
      recombinant form of human relaxin-2, a naturally occurring peptide hormone, has
      been found to significantly improve symptoms and signs of AHF, prevent in
      hospital worsening heart failure, as well as significantly improve 180-day
      cardiovascular and all-cause mortality after a 48-h infusion commenced within 16
      h of presentation (RELAX-AHF study). Available data suggest that the clinical
      benefits may be attributable to a potential combination of multiple actions of
      serelaxin, including improving systemic, cardiac, and renal hemodynamics, and
      protecting cells and organs from damage via anti-inflammatory, anti-cell death,
      anti-fibrotic, anti-hypertrophic, and pro-angiogenic effects. This manuscript
      describes the short- and long-term effects of serelaxin in AHF patients,
      analyzing how these effects can be explained by taking into account the range of
      hemodynamic and non-hemodynamic actions of serelaxin. In addition, this paper
      also addresses several aspects related to the role of serelaxin in the therapy of
      AHF that remain to be clarified and warrant further investigation.

PMID- 24590583
TI  - Two-tier regenerative response in liver failure in humans.
AB  - Acute and chronic liver failure is associated with high mortality. The enormous
      regenerative potential of the liver has generated a lot of attention. We
      undertook this work to assess the two-tier regenerative response in liver failure
      by immunohistochemistry and to correlate such response with liver histology in
      acute liver failure (ALF), acute-on-chronic liver failure (ACLF), and
      decompensated cirrhosis (CHD). Histological examination and immunohistochemical
      analysis of proliferating hepatocytes and activated hepatic progenitor cells
      (HPCs) were performed on the liver tissue of patients with ALF (25), ACLF (70),
      and CHD (70). Comparative analysis of regenerative markers and correlation with
      histological parameters were done in ALF, ACLF, and CHD. Hepatocytes proliferated
      significantly more in ALF in comparison to ACLF (p < 0.001) and CHD (p < 0.001).
      HPC proliferation was significantly higher in ACLF (p < 0.001) and CHD (p <
      0.001) than in ALF. ACLF patients showed the highest HPC proliferation and
      differentiation. Significantly more intermediate hepatocytes were found in ACLF
      than in ALF and CHD (p < 0.001). Marked parenchymal replacement by fibrosis
      and/or necrosis correlated significantly with activation of HPC in ACLF (p =
      0.01, odds ratio (OR) 4.95) and in CHD (p = 0.05, OR 4.19). The study of liver
      regeneration in human acute and chronic liver failure suggests that hepatocyte
      proliferation, providing the first line of regeneration response, is most active
      in ALF whereas HPC activation, the second line of defense, is more prominent in
      ACLF. More HPC differentiate to hepatocytes in ACLF than in CHD, reflecting
      better regenerative potential in ACLF.

PMID- 24590584
TI  - Variation in reporting of cancer extent and benign histology in prostate biopsies
      among European pathologists.
AB  - It is not known how uropathologists currently report histopathological features
      of prostate biopsies such as core length, tumor extent, perineural invasion, and
      non-tumor-associated features such as inflammation and hyperplasia in needle
      biopsies. A web-based survey was distributed among 661 members of the European
      Network of Uropathology. Complete replies were received from 266 pathologists in
      22 European countries. Total core lengths were reported by 64 %. The numbers of
      cores positive for cancer was given by 79 %. Linear cancer extent was reported by
      81 %, most often given in millimeters for each core (53 %) followed by the
      estimation of percentage of cancer in each core (40 %). A gap of benign tissue
      between separate cancer foci in a single core would always be subtracted by 48 %
      and by 63 % if cancer foci were minute and widely separated. Perineural invasion
      was reported by 97 %. Fat invasion by tumor was interpreted as extraprostatic
      extension by 81 %. Chronic and active/acute inflammation was always reported by
      32 and 56 % but only if pronounced by 54 and 39 %, respectively. While most (79
      %) would never diagnose benign prostatic hyperplasia on needle biopsy, 21 % would
      attempt to make this diagnosis. Reporting practices for prostate biopsies are
      variable among European pathologists. The great variation in some methodologies
      used suggests a need for further international consensus, in order for
      retrospective data to be comparable between different institutions.

PMID- 24590586
TI  - Comment on "long-term outcomes of children with umbilical vein varix diagnosed
      prenatally".

PMID- 24590585
TI  - APC alterations are frequently involved in the pathogenesis of acinar cell
      carcinoma of the pancreas, mainly through gene loss and promoter
      hypermethylation.
AB  - Genetic and epigenetic alterations involved in the pathogenesis of pancreatic
      acinar cell carcinomas (ACCs) are poorly characterized, including the frequency
      and role of gene-specific hypermethylation, chromosome aberrations, and copy
      number alterations (CNAs). A subset of ACCs is known to show alterations in the
      APC/beta-catenin pathway which includes mutations of APC gene. However, it is not
      known whether, in addition to mutation, loss of APC gene function can occur
      through alternative genetic and epigenetic mechanisms such as gene loss or
      promoter methylation. We investigated the global methylation profile of 34 tumor
      suppressor genes, CNAs of 52 chromosomal regions, and APC gene alterations
      (mutation, methylation, and loss) together with APC mRNA level in 45 ACCs and
      related peritumoral pancreatic tissues using methylation-specific multiplex
      ligation probe amplification (MS-MLPA), fluorescence in situ hybridization
      (FISH), mutation analysis, and reverse transcription-droplet digital PCR. ACCs
      did not show an extensive global gene hypermethylation profile. RASSF1 and APC
      were the only two genes frequently methylated. APC mutations were found in only 7
      % of cases, while APC loss and methylation were more frequently observed (48 and
      56 % of ACCs, respectively). APC mRNA low levels were found in 58 % of cases and
      correlated with CNAs. In conclusion, ACCs do not show extensive global gene
      hypermethylation. APC alterations are frequently involved in the pathogenesis of
      ACCs mainly through gene loss and promoter hypermethylation, along with reduction
      of APC mRNA levels.

PMID- 24590587
TI  - Response to "long-term outcomes of children with umbilical vein varix diagnosed
      prenatally".

PMID- 24590588
TI  - Response to "QF-PCR as a substitute for karyotyping of cytotrophoblast for the
      analysis of chorionic villi: advantages and limitations from a cytogenetic
      retrospective audit of 44 727 first-trimester prenatal diagnoses".

PMID- 24590589
TI  - Antibiotic prophylaxis for preventing post solid organ transplant tuberculosis.
AB  - BACKGROUND: Organ transplant recipients are at increased risk of infection as a
      result of immunosuppression caused inadvertently by medical treatment.
      Tuberculosis (TB) is a challenging infection to manage among organ transplant
      recipients that can be transmitted from infected people or triggered from latent
      infection. Organ transplant recipients have been reported to be up to 300 times
      more likely to develop TB than the general population. Consensus about the use of
      antibiotic prophylaxis to prevent post solid organ transplant TB has not been
      achieved. OBJECTIVES: This review assessed the benefits and harms of antibiotic
      prophylaxis to prevent post solid organ transplant TB. SEARCH METHODS: We
      searched the Cochrane Renal Group's Specialised Register up to 30 April 2013
      through contact with the Trials' Search Co-ordinator using search terms relevant
      to this review. Studies contained in the Specialised Register are identified
      through search strategies specifically designed for CENTRAL, MEDLINE and EMBASE
      and handsearching conference proceedings. SELECTION CRITERIA: All randomised
      controlled trials (RCTs) and quasi-RCTs that compared antibiotic prophylaxis with
      a placebo or no intervention for recipients of solid organ transplants were
      included. DATA COLLECTION AND ANALYSIS: Two authors independently assessed
      studies for inclusion and extracted data. We derived risk ratios (RR) for
      dichotomous data and mean differences (MD) for continuous data with 95%
      confidence intervals (CI). Methodological risk of bias was assessed using the
      Cochrane risk of bias tool. MAIN RESULTS: We identified three studies (10
      reports) that involved 558 kidney transplant recipients which met our inclusion
      criteria. All studies were conducted in countries that have high prevalence of TB
      (India and Pakistan), and investigated isoniazid, an oral antibacterial drug.
      Control in all studies was no antibiotic prophylaxis. Prophylactic administration
      of isoniazid reduced the risk of developing TB post-transplant (3 studies, RR
      0.35 95% CI 0.14 to 0.89), and there was no significant effect on all-cause
      mortality (2 studies, RR 1.39, 95% CI 0.70 to 2.78). There was however
      substantial risk of liver damage (3 studies, RR 2.74, 95% CI 1.22 to
      6.17).Reporting of methodological quality parameters was incomplete in all three
      studies. Overall, risk of bias was assessed as suboptimal. AUTHORS' CONCLUSIONS:
      Isoniazid prophylaxis for kidney transplant recipients reduced the risk of
      developing TB post-transplant. Kidney transplant recipients in settings that have
      high prevalence of TB should receive isoniazid during the first year following
      transplant. There is however, significant risk of liver damage, particularly
      among those who are hepatitis B or C positive. Further studies are needed among
      recipients of other solid organ transplants and in settings with low prevalence
      of TB to determine the benefits and harms of anti-TB prophylaxis in those
      populations.

PMID- 24590590
TI  - Endocrine responses, weight change, and energy sparing mechanisms during Ramadan
      among Gambian adolescent women.
AB  - OBJECTIVES: Ramadan fasting imposes a diurnal rather than a chronic energetic
      challenge. When Ramadan occurs during the agricultural season in subsistence
      populations, diurnal and chronic effects combine. The impact of layered energetic
      challenges on adolescent activity, metabolism, and body composition have not been
      quantified. This study compares the effects of a Ramadan (30 July-3 October 2009)
      and subsequent non-Ramadan (14 July-12 August 2010) agricultural season in 67
      Gambian subsistence agriculturalist women between 14 and 20 years old. METHODS:
      Researchers collected body composition, anthropometric, metabolic, and activity
      data. Metabolic hormones were measured in weekly urine (C-peptide of insulin) and
      serum (leptin). Energy expenditure was estimated from heart rate calibrated for
      oxygen consumption. RESULTS: Participants lost more weight (Wald Chi-square 8.7,
      P < 0.01) and lean mass (Wald Chi-square 4.7, P < 0.05) in Ramadan than in the
      non-Ramadan agricultural season. Energy expenditure was lower (Wald Chi-square
      11.2, P = 0.001) and there was a negative correlation between resting metabolic
      rate and energy expenditure in activity (R(2)  = 0.097, F = 5.366, P = 0.025)
      during Ramadan. Leptin and C-peptide were higher during Ramadan (Wald Chi-square
      53.7, P < 0.001 and Wald Chi-square 15.0, P < 0.001). CONCLUSIONS: Even using
      energy sparing behaviors, adolescent women enter negative energy balance when
      Ramadan and the agricultural season co-occur. Metabolic physiology shows a
      transient response to high glycemic index foods consumed at night. Older and
      larger individuals sustain greater losses during Ramadan.

PMID- 24590591
TI  - Caged peptides to control enzymatic activity within hydrogel scaffolds.
AB  - Enzyme-assisted 3D lithography: A peptide substrate for transglutaminase factor
      XIII (FXIIIa) can be caged with a photo-deprotectable group and immobilized to
      the hydrogel framework. The substrate can be decaged by using multiphoton light
      to anchor cell-signaling motifs in a spatial specific manner. 

PMID- 24590592
TI  - Pharmacokinetics of tolbutamide and its metabolite 4-hydroxy tolbutamide in
      poloxamer 407-induced hyperlipidemic rats.
AB  - Under hyperlipidemic conditions, there are likely to be alterations in the
      pharmacokinetics of CYP2C11 substrates following decreased expression of CYP2C11,
      which is homologous to human CYP2C9. The pharmacokinetics of tolbutamide (TB) and
      its metabolite 4-hydroxy tolbutamide (4-OHTB) were evaluated as a CYP2C11 probe
      after intravenous and oral administration of 10 mg/kg tolbutamide to poloxamer
      407-induced hyperlipidemic rats (HL rats). Changes in the expression and
      metabolic activity of hepatic CYP2C11 and the plasma protein binding of
      tolbutamide in HL rats were also evaluated. The total area under the plasma
      concentration-time curve (AUC) of tolbutamide in HL rats after intravenous
      administration was comparable to that in controls due to their comparable non
      renal clearance (CLNR ). The free fractions of tolbutamide in plasma were
      comparable between the control and HL rats. The 4-hydroxylated metabolite
      formation ratio (AUC4-OHTB /AUCTB ) in HL rats was significantly smaller than
      that in the control rats as a result of the reduced expression of hepatic CYP2C11
      (by 15.0%) and decreased hepatic CLint (by 28.8%) for metabolism of tolbutamide
      to 4-OHTB via CYP2C11. Similar pharmacokinetic changes were observed in HL rats
      after oral administration of tolbutamide. These findings have potential
      therapeutic implications, assuming that the HL rat model qualitatively reflects
      similar changes in patients with hyperlipidemia. Since other sulfonylureas in
      clinical use are substrates of CYP2C9, their hepatic CLint changes have the
      potential to cause clinically relevant pharmacokinetic changes in a
      hyperlipidemic state.

PMID- 24590593
TI  - Flexible and rigid amine-functionalized microporous frameworks based on different
      secondary building units: supramolecular isomerism, selective CO(2) capture, and
      catalysis.
AB  - We report the synthesis, structural characterization, and porous properties of
      two isomeric supramolecular complexes of ([Cd(NH2 ?bdc)(bphz)0.5 ]?DMF?H2 O}n
      (NH2 ?bdc=2-aminobenzenedicarboxylic acid, bphz=1,2-bis(4
      pyridylmethylene)hydrazine) composed of a mixed-ligand system. The first isomer,
      with a paddle-wheel-type Cd2 (COO)4 secondary building unit (SBU), is flexible in
      nature, whereas the other isomer has a rigid framework based on a MU-oxo-bridged
      Cd2 (MU-OCO)2 SBU. Both frameworks are two-fold interpenetrated and the pore
      surface is decorated with pendant -NH2 and ?N?N? functional groups. Both the
      frameworks are nonporous to N2 , revealed by the type II adsorption profiles.
      However, at 195 K, the first isomer shows an unusual double-step hysteretic CO2
      adsorption profile, whereas the second isomer shows a typical type I CO2 profile.
      Moreover, at 195 K, both frameworks show excellent selectivity for CO2 among
      other gases (N2 , O2 , H2 , and Ar), which has been correlated to the specific
      interaction of CO2 with the -NH2 and ?N?N? functionalized pore surface. DFT
      calculations for the oxo-bridged isomer unveiled that the -NH2 group is the
      primary binding site for CO2 . The high heat of CO2 adsorption (DeltaHads =37.7
      kJ mol(-1) ) in the oxo-bridged isomer is realized by NH2 ???CO2 /aromatic
      pi???CO2 and cooperative CO2 ???CO2 interactions. Further, postsynthetic
      modification of the -NH2 group into -NHCOCH3 in the second isomer leads to a
      reduced CO2 uptake with lower binding energy, which establishes the critical role
      of the -NH2 group for CO2 capture. The presence of basic -NH2 sites in the oxo
      bridged isomer was further exploited for efficient catalytic activity in a
      Knoevenagel condensation reaction. 

PMID- 24590594
TI  - A new high-frequency Agrobacterium-mediated transformation technique for Sesamum
      indicum L. using de-embryonated cotyledon as explant.
AB  - In spite of the economic importance of sesame (Sesamum indicum L.) and the recent
      availability of its genome sequence, a high-frequency transformation protocol is
      still not available. The only two existing Agrobacterium-mediated transformation
      protocols that are available have poor transformation efficiencies of less than
      2%. In the present study, we report a high-frequency, simple, and reproducible
      transformation protocol for sesame. Transformation was done using de-embryonated
      cotyledons via somatic embryogenic stages. All the critical parameters of
      transformation, like incubation period of explants in pre-regeneration medium
      prior to infection by Agrobacterium tumefaciens, cocultivation period,
      concentrations of acetosyringone in cocultivation medium, kanamycin
      concentration, and concentration of plant hormones, including 6
      benzylaminopurine, have been optimized. This protocol is superior to the two
      existing protocols in its high regeneration and transformation efficiencies. The
      transformed sesame lines have been tested by PCR, RT-PCR for neomycin
      phosphotransferase II gene expression, and beta-glucuronidase (GUS) assay. The
      regeneration frequency and transformation efficiency are 57.33 and 42.66%,
      respectively. T0 and T1 generation transgenic plants were analyzed, and several
      T1 plants homozygous for the transgenes were obtained.

PMID- 24590595
TI  - The changing face of anticoagulation management: an improving countenance.

PMID- 24590596
TI  - Investigation of cenderitide controlled release platforms for potential local
      treatment of cardiovascular pathology.
AB  - In this work, we focused on the development and investigation of controlled
      release matrices for a novel cardiotherapeutic peptide, cenderitide (CD-NP) that
      has shown to be useful for control of ventricular remodeling. To circumvent the
      hydrophilicity disparity between CD-NP and hydrophobic polymer matrix, a
      cosolvent system (water/dichloromethane) was selected for investigation. The
      effect of emulsification conditions, addition of poly(ethylene glycol) (PEG) and
      its copolymer on the release mechanism and profile were investigated. To verify
      the retention of bioactivity of entrapped CD-NP in different formulations, the
      generation of 3',5' cyclic guanosine monophospate (cGMP) and the inhibition of
      human cardiac fibroblast (HCF) were evaluated. The results showed that neat
      poly(epsilon-caprolactone) matrices carried out via two distinct emulsification
      conditions had either an unacceptably high burst or incomplete release of CD-NP;
      and the addition of PEG and its copolymer obtained intermediate profiles. Our
      confocal laser scanning microscopy and surface morphological investigations
      showed that the copolymer excipient was superior in playing stabilizer role by
      colocalizing and redistributing peptide throughout the matrix, making the release
      less sensitive to emulsification conditions. Furthermore, the released CD-NP is
      able to generate the cGMP and inhibit the HCF proliferation. Our investigations
      showed that CD-NP-loaded platforms can be a feasible option to provide sustained
      antifibrotic moderation of fibrotic scar formation and be potentially used to
      alleviate the adverse effects of cardiac remodeling.

PMID- 24590597
TI  - Construction of mesoporous frameworks with vanadoborate clusters.
AB  - A new porous vanadoborate was synthesized by employing the scale chemistry theory
      with the vanadoborate cluster V10B28. The twofold interpenetrated lvt network was
      assembled with zinc-containing elliptical vanadoborate clusters and Zn polyhedra.
      The single lvt framework contains a three-dimensional 38*38*20 ring channel
      system with the pore size (24.7*12.7 A) reaching the mesoscale, thus indicating
      the possibility of constructing 3D ordered mesopores with vanadoborate clusters.
      The porosity of the SUT-7 structure was confirmed by CO2 adsorption of the as
      synthesized materials.

PMID- 24590598
TI  - Synthesis of indazoles and azaindazoles by intramolecular aerobic oxidative C-N
      coupling under transition-metal-free conditions.
AB  - A transition-metal-free oxidative C-N coupling method has been developed for the
      synthesis of 1H-azaindazoles and 1H-indazoles from easily accessible hydrazones.
      The procedure uses TEMPO, a basic additive, and dioxygen gas as the terminal
      oxidant. This reaction demonstrates better reactivity, functional group
      tolerance, and broader scope than comparable metal catalyzed reactions.

PMID- 24590599
TI  - Effect of a thymol application on olfactory memory and gene expression levels in
      the brain of the honeybee Apis mellifera.
AB  - Essential oils are used by beekeepers to control the Varroa mites that infest
      honeybee colonies. So, bees can be exposed to thymol formulations in the hive.
      The effects of the monoterpenoid thymol were explored on olfactory memory and
      gene expression in the brain of the honeybee. In bees previously exposed to
      thymol (10 or 100 ng/bee), the specificity of the response to the conditioned
      stimulus (CS) was lost 24 h after learning. Besides, the octopamine receptor OA1
      gene Amoa1 showed a significant decrease of expression 3 h after exposure with 10
      or 100 ng/bee of thymol. With the same doses, expression of Rdl gene, coding for
      a GABA receptor subunit, was not significantly modified but the trpl gene was
      upregulated 1 and 24 h after exposure to thymol. These data indicated that the
      genes coding for the cellular targets of thymol could be rapidly regulated after
      exposure to this molecule. Memory and sensory processes should be investigated in
      bees after chronic exposure in the hive to thymol-based preparations. 

PMID- 24590600
TI  - Congener-specific accumulation and environmental risk assessment of
      polybrominated diphenyl ethers in diverse Korean sewage sludge types.
AB  - Industrial, domestic wastewater, and livestock sludge samples were collected from
      23 wastewater treatment plants in Korea and analyzed for polybrominated diphenyl
      ethers (PBDEs). The concentrations of Sigma19PBDE ranged from 4.01 to 10,400 ng/g
      dry weight. The average Sigma19PBDE concentrations in industrial, domestic
      wastewater, and livestock sludge were 1,560 +/- 3,610, 402 +/- 148, and 27.6 +/-
      50.4 ng/g dry weight, respectively. The composition of PBDEs differed according
      to the type of sludge. Among the PBDE congeners, BDE 209 was dominant in all
      sludge samples. After BDE 209, relatively high levels were found for BDE 28 and
      47 from industrial sludge, BDE 47 and 99 from domestic wastewater sludge, and BDE
      206, 207, and 208 from livestock sludge. Using hierarchical cluster analysis,
      sludges were divided into three groups according to PBDE congener composition. A
      risk assessment of PBDEs in sludge used for soil amendment was carried out.
      Preliminary results indicated that the potential risk of soil exposed to PBDEs in
      sludge was relatively low. 

PMID- 24590601
TI  - Degradation of 1,4-dioxane in water with heat- and Fe(2+)-activated persulfate
      oxidation.
AB  - This research investigated the 1,4-dioxane (1,4-D) degradation efficiency and
      rate during persulfate oxidation at different temperatures, with and without
      Fe(2+) addition, also considering the effect of pH and persulfate concentration
      on the oxidation of 1,4-D. Degradation pathways for 1,4-D have also been proposed
      based on the decomposition intermediates and by-products. The results indicate
      that 1,4-D was completely degraded with heat-activated persulfate oxidation
      within 3-80 h. The kinetics of the 1,4-D degradation process fitted well to a
      pseudo-first-order reaction model. Temperature was identified as the most
      important factor influencing the 1,4-D degradation rate during the oxidation
      process. As the temperature increased from 40 to 60  degrees C, the degradation
      rate improved significantly. At 40  degrees C, the addition of Fe(2+) also
      increased the 1,4-D degradation rate. Interestingly, at 50 and 60  degrees C, the
      1,4-D degradation rate decreased slightly with the addition of Fe(2+). This
      reduced degradation rate may be attributed to the rapid conversion of Fe(2+) to
      Fe(3+) and the production of an Fe(OH)3 precipitate which limited the ultimate
      oxidizing capability of persulfate with Fe(2+) under higher temperatures. Higher
      persulfate concentrations led to higher 1,4-D degradation rates, but pH
      adjustment had no significant effect on the 1,4-D degradation rate. The
      identification of intermediates and by-products in the aqueous and gas phases
      showed that acetaldehyde, acetic acid, glycolaldehyde, glycolic acid, carbon
      dioxide, and hydrogen ion were generated during the persulfate oxidation process.
      A carbon balance analysis showed that 96 and 93% of the carbon from the 1,4-D
      degradation were recovered as by-products with and without Fe(2+) addition,
      respectively. Overall, persulfate oxidation of 1,4-D is promising as an
      economical and highly efficient technology for treatment of 1,4-D-contaminated
      water.

PMID- 24590602
TI  - Comparative study of mercury speciation in commercial fishes of the Brazilian
      Amazon.
AB  - Mercury is responsible for serious episodes of environmental pollution throughout
      the world, especially in the Amazon. This toxicity has led regulatory agencies to
      focus on fish as the target organism for protecting the health of humans and
      other sensitive organisms. Unfortunately, in the Amazon area, different sampling
      strategies and the wide variety of sampling areas and fish species make it
      extremely difficult to determine relationships across geographic regions or over
      time to ascertain historical trends. Thus, the aim of this work was to achieve
      three main objectives: a comparative study of mercury contamination in fish of
      Itaituba (Tapajos, located downstream of the largest gold-mining region in
      Amazon) and Belem (an area non-exposed to mercury pollution of anthropogenic
      origin), perform an analysis of inorganic mercury (IHg) versus monomethylmercury
      (MeHg) contents, and, finally, compare mercury contamination in Tapajos over
      time. Five piscivorous species were obtained in Itaituba and Belem. Also, four
      non-piscivorous species were collected in Itaituba. For the first time, mercury
      speciation showed that (1) current MeHg levels in piscivorous species in Tapajos
      are higher than those of the non-exposed area, (2) piscivorous species from
      Itaituba (dourada, filhote, and sarda) contained mercury levels above the World
      Health Organization safety limit (~17%) and/or above the US Environmental
      Protection Agency tissue residue criterion (40%), (3) increased MeHg is usually
      accompanied by increased IHg, and (4) the mean total mercury concentrations for
      piscivorous species in Itaituba were within the same range and, associated
      uncertainties as those previously reported, although a remarkable decreasing
      trend over time was observed for mean total Hg concentrations in non-piscivorous
      species from Itaituba. The present study supports the importance of continuous
      monitoring of both populations in the Amazon Rivers. Our results will better
      assist the development of preventive strategies and governmental actions to
      confront the problem of mercury contamination in the Amazon.

PMID- 24590603
TI  - Soil microbial systems respond differentially to tetracycline,
      sulfamonomethoxine, and ciprofloxacin entering soil under pot experimental
      conditions alone and in combination.
AB  - This study investigated soil microbial responses to the application of
      tetracycline (TC), sulfamonomethoxine (SMM), and ciprofloxacin (CIP) alone and in
      combination in a soil culture pot experiment conducted at Hangzhou, China.
      Multiple approaches were applied for a better and complete depiction. Among the
      three antibiotics, SMM has a lowest dissipation and shows a most dramatic
      inhibition on microbial community and metabolism diversity. The combined
      application (AM) of SMM, CIP, and TC improved the dissipation of each antibiotic;
      similarly, SMM- and CIP-resistant bacteria showed larger populations in the AM
      than all single applications. Soils accumulated a large content of NO3-N at day
      20 after multi-antibiotics perturbation. All antibiotics stimulated soil basal
      respirations and inhibited soil metabolism diversity, whereas the interruption
      exerted by SMM and AM lasted for a longer time. Six nitrogen-cycling genes
      including chiA, amoA, nifH, nirK, nirS, and narG were quantified and found to
      decrease owing to both single- and multi-antibiotics perturbation. Overall, AM
      was most interruptive for soils, followed by SMM perturbation, while other
      antibiotics could be less interruptive. These results provide systematic insights
      into how soil microbial systems would shift under each single- or multi
      antibiotics perturbation. 

PMID- 24590604
TI  - Characterization of cadmium uptake, translocation, and distribution in young
      seedlings of two hot pepper cultivars that differ in fruit cadmium concentration.
AB  - The reasons why some cultivars of hot pepper (Capsicum annuum L.) accumulate low
      levels of Cd are poorly understood. We aimed to compare the characteristics of Cd
      uptake and translocation in low-Cd and high-Cd hot pepper cultivars by
      determining the subcellular locations and chemical forms of Cd, and its
      distribution among different plant organs. We conducted a hydroponic experiment
      to investigate the subcellular distribution and chemical forms of Cd in roots,
      stems, and leaves of a low-Cd (Yeshengchaotianjiao, YCT) and a high-Cd cultivar
      (Jinfuzaohuangjiao, JFZ). The results showed that the concentrations of Cd in
      almost all subcellular fractions of roots, and in all chemical forms in roots,
      were higher in YCT than in JFZ. Compared with YCT, JFZ had higher Cd
      concentrations in almost all subcellular fractions of stems and leaves, and
      higher Cd concentrations in almost all chemical forms in stems and leaves.
      Additionally, YCT had significantly higher total Cd accumulation but a lower Cd
      translocation rate compared with JFZ. In general, the results presented in this
      study revealed that root-to-shoot Cd translocation via the xylem is the key
      physiological processes determining the Cd accumulation level in stems and leaves
      of hot pepper plants. Immobilization of Cd by the cell walls of different organs
      is important in Cd detoxification and limiting the symplastic movement of Cd. 

PMID- 24590606
TI  - Clinician use of standardized assessments following a common elements
      psychotherapy training and consultation program.
AB  - Despite increasing emphasis on the implementation of evidence-based treatments in
      community service settings, little attention has been paid to supporting the use
      of evidence-based assessment (EBA) methods and processes, a parallel component of
      evidence-based practice. Standardized assessment (SA) tools represent a key
      aspect of EBA and are central to data-driven clinical decision making. The
      current study evaluated the impact of a statewide training and consultation
      program in a common elements approach to psychotherapy. Practitioner attitudes
      toward, skill applying, and use of SA tools across four time points (pre
      training, post-training, post-consultation, and follow-up) were assessed. Results
      indicated early increases in positive SA attitudes, with more gradual increases
      in self-reported SA skill and use. Implications for supporting the sustained use
      of SA tools are discussed, including the use of measurement feedback systems,
      reminders, and SA-supportive supervision practices. 

PMID- 24590607
TI  - A fervent plea for second-order toxicology.

PMID- 24590609
TI  - The Incidence of Problem Gambling in a Representative Cohort of Swedish Female
      and Male 16-24 Year-Olds by Socio-demographic Characteristics, in Comparison with
      25-44 Year-Olds.
AB  - We aimed to estimate the incidence of a first episode of problem gambling among
      Swedish 16-24 year-olds by demographic and socio-economic characteristics, and to
      compare the incidence between 16-24 and 25-44 year-olds, and between young women
      and men. Other aims were to estimate the proportions of recovery and incidence in
      recurrent problem gambling, and prevalence of problem gambling among 16-44 year
      olds in Sweden. We selected 4,358 participants aged 16-44 from the nationally
      representative Swedish Longitudinal Gambling Study in 2008/2009 and 2009/2010.
      The primary outcome measure was a first episode of problem gambling during 12
      months before the follow-up as measured by the Problem Gambling Severity Index
      among participants without a history of problem gambling at baseline. The
      incidence proportion of a first episode of problem gambling among 16-24 year-olds
      was 2.26% (95% confidence interval 1.52-3.36); three times lower among females
      (1.14; 0.42-3.07%) than males (3.32; 2.19-5.01%). Young age and household
      financial problems were associated with first episode problem gambling among
      young women. Among 25-44 year-olds, the incidence proportion of a first episode
      of problem gambling was 0.81% (0.41-1.56). Recovery from problem gambling was
      high, in particular among females. Individual transitions from problem gambling
      to recovery and to recurrent problem gambling, between baseline and follow-up,
      were common regardless of age. This study adds further evidence to research
      suggesting that there is a high mobility in and out of problem gambling over time
      on an individual level. The high incidence of first episode problem gambling
      among youth in Sweden stresses the importance of prevention of problem gambling
      at an early age.

PMID- 24590608
TI  - Iron and atherosclerosis: nailing down a novel target with magnetic resonance.
AB  - Iron is an essential mineral in many proteins and enzymes in human physiology,
      with limited means of iron elimination to maintain iron balance. Iron accrual
      incurs various pathological mechanisms linked to cardiovascular disease. In
      atherosclerosis, iron catalyzes the creation of reactive oxygen free radicals
      that contribute to lipid modification, which is essential to atheroma formation.
      Inflammation further fuels iron-related pathologic processes associated with
      plaque progression. Given iron's role in atherosclerosis development, in vivo
      detection techniques sensitive iron are needed for translational studies
      targeting iron for earlier diagnosis and treatment. Magnetic resonance imaging is
      uniquely able to quantify iron in human tissues noninvasively and without
      ionizing radiation, offering appealing for longitudinal and interventional
      studies. Particularly intriguing is iron's complementary biology vs. calcium,
      which is readily detectable by computed tomography. This review summarizes the
      role of iron in atherosclerosis with considerable implications for novel
      diagnostic and therapeutic approaches. 

PMID- 24590610
TI  - Integrated approach to the in vivo genotoxic effects of a titanium dioxide
      nanomaterial using LacZ plasmid-based transgenic mice.
AB  - Titanium dioxide (TiO2 ) nanomaterials (NMs) are widely used in a diversity of
      products including cosmetics, pharmaceuticals, food, and inks, despite
      uncertainties surrounding the potential health risks that they pose to humans and
      the environment. Previous studies on the genotoxicity of TiO2 have reported
      discrepant or inconclusive findings in both in vitro and in vivo systems. This
      study explores the in vivo genotoxic potential of a well-characterized uncoated
      TiO2 NM with an average diameter of 22 nm (NM-102, from JRC repository) using
      several genotoxicity endpoints in the LacZ plasmid-based transgenic mouse model.
      Mice were exposed by intravenous injection to two daily doses of NM-102: 10 and
      15 mg/kg of body weight/day. Micronuclei were analyzed in peripheral blood
      reticulocytes 42 hr after the last treatment. DNA strand breaks (comet assay) and
      gene mutations were determined in the spleens and livers of the same animals 28
      days after the last treatment. Histopathological and cytological analyses were
      also performed in liver samples. Genotoxic effects were not detected in mice
      exposed to the nanosized TiO2 under the experimental conditions used, despite a
      moderate inflammatory response that was observed in the liver. Considering the
      biopersistence of TiO2 in mouse liver and the moderate inflammatory response, the
      possibility of a secondary genotoxic effect at higher doses and in conditions
      that result in a stronger inflammatory response, for example, within a longer
      time window, should be investigated further.

PMID- 24590611
TI  - Variation in the spillover effects of illness on parents, spouses, and children
      of the chronically ill.
AB  - BACKGROUND: Given the broad scope of the spillover effects of illness, it is
      important to characterize the variability in these outcomes to identify
      relationship types in which secondary impacts of illness are particularly
      important to include in health economic evaluations. PURPOSE: To examine
      heterogeneity in spillover effects of chronic conditions on family members by
      type of familial relationship with patient. METHODS: Adults (aged >=18 years) and
      adolescents (aged 13-17 years) who had a parent, spouse, or child in their
      household with a chronic condition (Alzheimer's disease/dementia, arthritis,
      cancer, or depression) were recruited from a US national panel to participate in
      an on-line survey. Respondents were asked to rate the spillover effect of their
      family member's illness on their own health on a 0-100 scale, with lower scores
      indicating greater spillover. Regression analysis was used to evaluate the
      association between rating scale scores and relationship with an ill family
      member (ill parent, child, or spouse) for each illness separately, controlling
      for caregiving responsibility and the health status of the ill family member.
      RESULTS: 1,267 adults and 102 adolescents met inclusion criteria. In adjusted
      analyses, having a sick child was significantly (p < 0.05) associated with lower
      rating scale scores compared with having a spouse with the same condition
      (cancer: -24.2; depression -9.7). Having a non-elderly or elderly adult parent
      with a condition, compared with a spouse, was significantly associated with lower
      rating scale scores for arthritis (-3.8) and depression (-5.3), but not for
      Alzheimer's disease/dementia or cancer. CONCLUSIONS: The impact of illness on
      family members, measured with a rating scale, varies by relationship type for
      certain illnesses. Having a child with cancer, a parent with arthritis, or either
      with depression, is significantly associated with greater spillover, compared
      with having a spouse with one of these conditions.

PMID- 24590616
TI  - Kinetic modeling of hydrogen abstractions involving sulfur radicals.
AB  - One of the requisites for the development of detailed reaction networks is the
      availability of accurate kinetic data. Group additivity based models linking the
      Arrhenius parameters to structural characteristics of the transition state have
      proven to be a valuable tool to obtain those data. In this work, group additivity
      values are presented to allow a broad range of C?H and S?H hydrogen abstraction
      reactions by S radicals to be modeled. Rate coefficients in the temperature range
      from 300 to 1500 K are obtained by using the CBS-QB3 method in the high-pressure
      limit and are corrected for tunneling and anharmonicity of rotation about the
      transitional bond. A total of 149 reactions are studied. From these reactions, a
      total of 52 group additivity values and 35 resonance corrections are derived. The
      general applicability of the group additivity method is demonstrated for a test
      set containing 25 reactions. At 300 K, rate coefficients are on average
      reproduced within a factor of 2.8. The mean absolute deviations on the Arrhenius
      parameters are 2 kJ mol(-1) for the activation energy and 0.38 for log A in which
      A is the pre-exponential factor. 

PMID- 24590617
TI  - Temperature dependence of the properties of water and its solutes, including the
      supercooled region.
AB  - An earlier study on the properties of supercooled water and some solutes obtained
      by simple graphical extrapolation of data available in the literature, determined
      above the freezing point, led to the hypothesis that water could have a
      temperature of structural arrest at t0 =-30  degrees C for H2 O and -22  degrees
      C for D2 O. From the present investigation of many more properties of a widely
      varied nature, this discovery is confirmed throughout. The method is compared
      with the classical logarithmic Arrhenius and van't Hoff methods that predict t0
      always to occur at 0 K, and with the more recently used power law dependence
      method. With the latter, extrapolated plots intersect the temperature axis at or
      near to a value of ts =-45  degrees C, that is, systematically more negative than
      t0 . It is argued that this ts value, which is the so-called singularity
      temperature, is likely to be an artefact. It is suggested that, instead of using
      modified van 't Hoff or Arrhenius relationships to describe temperature
      dependences in the full temperature range, polynomials in (t-t0 ) should be used.

PMID- 24590618
TI  - A novel mechanism for the extraction of metals from water to ionic liquids.
AB  - We present a novel mechanism for the extraction of metals from aqueous phases to
      room-temperature ionic liquids (ILs) by use of a high-temperature salt as an
      extraction agent. The mechanism capitalizes on the fact that charged metal
      complexes are soluble in ILs; this allows for extraction of charged complexes
      rather than the neutral species, which are formed by conventional approaches. The
      use of a well-chosen extraction agent also suppresses the competing ion-exchange
      mechanism, thus preventing degradation of the ionic liquid. The approach permits
      the use of excess extractant to drive the recovery of metals in high yield. This
      work presents both a thermodynamic framework for understanding the approach and
      experimental verification of the process in a range of different ILs. The method
      has great potential value in the recovery of metals, water purification and
      nuclear materials processing. 

PMID- 24590619
TI  - Use of ADHD medication during pregnancy from 1999 to 2010: a Danish register
      based study.
AB  - OBJECTIVE: This study aimed to describe the trends in use of Attention Deficit
      Hyperactivity Disorders (ADHD) medication during pregnancy in Denmark from 1999
      to 2010, as well as to explore characteristics of women who use ADHD medication
      during pregnancy and whether exposure is associated with outcome of pregnancy.
      METHOD: A linkage between various Danish national health registries was performed
      to identify all recorded pregnancies from 1999 to 2010. Use of ADHD medication
      was defined as a redeemed prescription on methylphenidate, modafinil, or
      atomoxetine from 28 days prior to the first day of the last menstrual period
      until the end of pregnancy. RESULTS: Of the 1 054 494 registered pregnancies, 480
      were exposed to ADHD medication. From 2003 to the first quarter of 2010, use of
      ADHD medication during pregnancy increased from 5 to 533 per 100 000 person
      years. A similar increase was observed among Danish women of childbearing age.
      Compared with unexposed, women who used ADHD medication during pregnancy were
      more often younger, single, lower educated, received social security benefits,
      and used other psychopharmaca. Exposed pregnancies were more likely to result in
      induced abortions on maternal request (odds ratio = 4.70, 95%CI = 3.77-5.85),
      induced abortions on special indication (odds ratio = 2.99, 95%CI = 1.34-6.67),
      and miscarriage (odds ratio = 2.07, 95%CI = 1.51-2.84) compared with unexposed
      pregnancies. CONCLUSIONS: The number of pregnancies exposed to ADHD medication
      has increased similarly to the increase in use of ADHD medication among women of
      childbearing age. Use of ADHD medication in pregnancy was associated with
      different indicators of maternal disadvantage and with increased risk of induced
      abortion and miscarriage.

PMID- 24590620
TI  - Influence of daily immersion in denture cleanser on multispecies biofilm.
AB  - OBJECTIVE: The aim of this study was to evaluate the effect of daily exposure to
      a denture cleanser on a multispecies biofilm. MATERIALS AND METHODS: Multispecies
      biofilms (five bacteria and Candida albicans) were developed for 64.5 h on
      acrylic resin specimens and randomized into control and experimental groups. In
      the experimental group, biofilms were immersed in denture cleanser for 3 min/day
      for seven consecutive days. In the control group, the biofilms were developed
      with no treatment for the same period. Biofilms from both groups were collected
      after 1, 4, and 7 days and analyzed for the number of microorganisms and
      polysaccharide concentrations. Scanning electron microscopy (SEM) and confocal
      microscopy (CLSM) analyses were performed. RESULTS: The total microorganism
      counts and bacterial populations were lower in the experimental group compared to
      the control group for all of the periods evaluated. However, the C. albicans
      counts continuously increased in all of the cleanser-exposed biofilms, with
      abundant hyphae forms on SEM and CLSM images. The polysaccharide concentration
      was significantly higher in the experimental group after 7 days. CONCLUSIONS:
      Daily exposure of a multispecies biofilm to a denture cleanser reduces the number
      of total microorganisms but favors C. albicans development. CLINICAL RELEVANCE:
      Daily use of denture cleanser is an effective method for controlling bacteria in
      biofilm, but it can potentially select C. albicans, an important etiological
      agent of oral candidosis.

PMID- 24590621
TI  - Synthesis and spin-trapping properties of a trifluoromethyl analogue of DMPO: 5
      methyl-5-trifluoromethyl-1-pyrroline N-oxide (5-TFDMPO).
AB  - The 5-diethoxyphosphonyl-5-methyl-1-pyrroline N-oxide superoxide spin adduct
      (DEPMPO-OOH) is much more persistent (about 15 times) than the 5,5-dimethyl-1
      pyrroline N-oxide superoxide spin adduct (DMPO-OOH). The diethoxyphosphonyl group
      is bulkier than the methyl group and its electron-withdrawing effect is much
      stronger. These two factors could play a role in explaining the different half
      lifetimes of DMPO-OOH and DEPMPO-OOH. The trifluoromethyl and the
      diethoxyphosphonyl groups show similar electron-withdrawing effects but have
      different sizes. We have thus synthesized and studied 5-methyl-5-trifluoromethyl
      1-pyrroline N-oxide (5-TFDMPO), a new trifluoromethyl analogue of DMPO, to
      compare its spin-trapping performance with those of DMPO and DEPMPO. 5-TFDMPO was
      prepared in a five-step sequence by means of the Zn/AcOH reductive cyclization of
      5,5,5-trifluoro-4-methyl-4-nitropentanal, and the geometry of the molecule was
      estimated by using DFT calculations. The spin-trapping properties were
      investigated both in toluene and in aqueous buffer solutions for oxygen-, sulfur
      , and carbon-centered radicals. All the spin adducts exhibit slightly different
      fluorine hyperfine coupling constants, thereby suggesting a hindered rotation of
      the trifluoromethyl group, which was confirmed by variable-temperature EPR
      studies and DFT calculations. In phosphate buffer at pH 7.4, the half-life of 5
      TFDMPO?OOH is about three times shorter than for DEPMPO-OOH and five times longer
      than for DMPO-OOH. Our results suggest that the stabilization of the superoxide
      adducts comes from a delicate balance between steric, electronic, and hydrogen
      bonding effects that involve the beta group, the hydroperoxyl moiety, and the
      nitroxide.

PMID- 24590622
TI  - Evidence for divergent effects of neurodegeneration in Huntington's disease on
      attentional selection and neural plasticity: implications for excitotoxicity.
AB  - It is generally assumed that neurodegeneration leads to declines in cognitive
      functions. However, there is evidence that neurodegenerative processes related to
      excitotoxicity can lead to paradoxical improvements in circumscribed cognitive
      functions, while at the same time other processes are compromised. An open
      question is how such paradoxical improvements reported in literature and declines
      usually associated with neurodegeneration relate to each other. Do paradoxical
      improvements only reflect a transient phenomenon, or do they intensify in the
      course of neurodegeneration? We examine this question using behavioral and
      neurophysiological (EEG) data in a human model of excitotoxic neurodegeneration
      (i.e., Huntington's disease, HD). The results show that attentional selection
      processes decline during pre-manifest disease progression. Importantly, the
      efficacy of protocols used to induce neural plasticity in processes underlying
      attentional selection processes also increases in course of ongoing
      neurodegeneration in pre-manifest HD. This was reflected in behavioral data and
      electrophysiological correlates of processes related to the allocation of
      attention. To conclude, our results suggest that circumscribed enhancements of
      specific cognitive functions are as much a result of the developmental process of
      neurodegeneration as the well-known detrimental effects. The results account for
      the divergent effects of neurodegenerative processes closely related to
      excitotoxicity on cognitive functions. 

PMID- 24590623
TI  - Different unfractionated heparin doses for preventing arterial thrombosis in
      children undergoing cardiac catheterization.
AB  - BACKGROUND: The role of cardiac catheterization in pediatrics has progressed
      significantly over the last two decades, evolving from a primary diagnostic tool
      to a primary treatment modality in children with congenital heart disease.
      Vascular complications, particularly arterial thrombosis, are among the most
      common unwanted post-cardiac catheterization events. In 1974, unfractionated
      heparin proved to be superior to placebo in decreasing the incidence of arterial
      thrombosis in pediatric patients. However, the optimal dose of unfractionated
      heparin to be utilized in this setting remains a matter of controversy.
      OBJECTIVES: To evaluate the use of low-dose (< 100 units/kg) versus high-dose (>=
      100 units/kg) unfractionated heparin administered as an intravenous bolus at the
      time of initiation of cardiac catheterization (that is, immediately after
      arterial puncture), with or without subsequent heparin maintenance doses, for the
      prevention of post-procedural arterial thrombosis in children. SEARCH METHODS:
      The Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator
      searched the Specialised Register (last searched November 2013) and CENTRAL
      (2013, Issue 10). The authors searched MEDLINE, EMBASE, and the Virtual Health
      Library. Clinical trials databases and sources of grey literature were searched.
      No language restrictions were applied. SELECTION CRITERIA: Randomized or quasi
      randomized trials that compared low dose to high dose unfractionated heparin
      administered prior to cardiac catheterization were included. We selected studies
      conducted in children aged 0 to 18 years. DATA COLLECTION AND ANALYSIS: The first
      screening of potentially eligible studies was conducted by one of the authors
      (MLA). The second screening, quality assessment and data extraction were
      independently conducted by two authors (MLA, LRB). Outcomes (thrombotic events,
      bleeding complications, other complications) were treated as dichotomous
      variables. The effect measures used were risk ratio (RR), risk difference (RD)
      and number needed to treat (NNT), with 95% confidence intervals (CI). MAIN
      RESULTS: Two studies with a total of 492 participants were eligible for
      inclusion. Risk of bias was low for all domains in one of the studies and unclear
      for the other. One of the trials was stopped early. The quality of evidence for
      our key outcomes was moderate. The CI for the risk of arterial thrombotic events
      was compatible with benefits of either high or low unfractionated heparin dose
      regimens (RR low-dose versus high-dose 1.06, 95% CI 0.58 to 1.92). Only one of
      the studies reported the frequency of bleeding events for the cohort of patients
      and found no statistically significant difference in the incidence of major and
      minor bleeding events between arms (RR low-dose versus high-dose 1.38, 95% CI
      0.46 to 4.13 for minor bleeding; RR low-dose versus high-dose 2.96, 95% CI 0.12
      to 71.34 for major bleeding events). This study also reported on the incidence of
      deep vein thrombosis when comparing the high versus low dose of heparin and
      reported a non-significant difference (RR low-dose versus high-dose 0.34, 95% CI
      0.01 to 8.28). The other study lacked information about bleeding. Side effects of
      heparin other than bleeding complications were not reported in either of the
      studies. AUTHORS' CONCLUSIONS: Due to the limitations of the current evidence,
      small number of included studies, and lack of details reported in one study, we
      are unable to determine the effects of different dosing regimens of
      unfractionated heparin for the prevention of vascular thrombosis during cardiac
      catheterization in children. A further adequately powered, randomized clinical
      trial is needed.

PMID- 24590624
TI  - Methyl-beta-cyclodextrins: the role of number and types of substituents in
      solubilizing power.
AB  - Methylated cyclodextrins (CDs) are effective solubilizers of poorly soluble
      organic compounds. In this work, we compared various methylated beta-CDs
      concerning their structure characterized by nuclear magnetic resonance
      spectroscopy, composition analyzed by HPLC and solubilizing capability by using
      model compounds such as cholesterol, fatty acids, furosemide, tamoxifen, and
      amiodarone. All the commercially available methylated beta-CDs are mixtures of
      various isomers and homologues except trimethyl beta-CD. The effects of the
      degree of methylation, the composition, as well as the influence of further
      derivatization with ionic groups were studied. The number of methyl groups in a
      CD ring should be around 14 to get the highest solubility for the included guest
      molecules. Although the distribution of isomers and related compounds has hardly
      any effect at constant degree of substitution, the introduction of amino and
      succinyl moieties on the CD ring adds ionic interactions to the hydrophobic
      interactions of the inclusion complex formation, which might result in synergic
      effect in solubilization.

PMID- 24590625
TI  - Selective host-guest interactions of a transformable coordination capsule/tube
      with fullerenes.
AB  - An M2L4 coordination capsule or an M2L2 coordination tube was selectively formed
      by the combination of Hg(II) hinges and bent bispyridine ligands. The two
      structures reversibly interconvert at room temperature in response to modulation
      of the metal-to-ligand ratio and exhibit different host-guest interaction
      behavior. The capsule alone encapsulates large spherical molecules, fullerenes
      C60 and C70, and the bound guests are released upon capsule-to-tube
      transformation by the simple addition of metal ions.

PMID- 24590627
TI  - Sexual initiation and emotional/behavioral problems in Taiwanese adolescents: a
      multivariate response profile analysis.
AB  - This study aimed to investigate the relations of adolescent sexual experiences
      (particularly early initiation) to a spectrum of emotional/behavioral problems
      and to probe possible gender difference in such relationships. The 10th (N =
      8,842) and 12th (N = 10,083) grade students, aged 16-19 years, participating in
      national surveys in 2005 and 2006 in Taiwan were included for this study. A self
      administered web-based questionnaire was designed to collect information on
      sociodemographic characteristics, sexual experience, substance use, and the Youth
      Self-Report Form. For the sexually experienced adolescents, their sexual
      initiation was classified as early initiation (<16 years) or non-early initiation
      (16-19 years). Gender-specific multivariate response profile regression was used
      to examine the relationship between sexual experience and the behavioral
      syndromes. Externalizing problems, including Rule-breaking Behavior and
      Aggressive Behavior, were strongly associated with sexual initiation in
      adolescence; the magnitude of the association increased for earlier sexual
      initiation, especially for females. As to internalizing problems, the connection
      was rather heterogeneous. The scores on some syndromes, such as Somatic
      Complaints and Anxious/Depressed, were higher only for females with early or non
      early sexual initiation whereas the score on Withdrawn, along with Social
      Problems that is neither internalizing nor externalizing, was lower for the
      sexually experienced adolescents than for the sexually inexperienced ones. We
      concluded that earlier sexual initiation was associated with a wider range of
      behavioral problems in adolescents for both genders, yet the increased risk with
      emotional problems was predominately found in females. 

PMID- 24590626
TI  - Association between subjective well-being and exceptional longevity in a
      longevity town in China: a population-based study.
AB  - To examine the associations of cognitive and emotional facets (measured by life
      satisfaction [LS], positive affect [PA], negative affect [NA], and affect balance
      [AB]) of subjective well-being (SWB) with exceptional longevity (EL), we
      conducted a population-based study with 463 EL individuals (95+, EL group)
      recruited from a longevity town of Rugao, China (N = 755, with a response rate of
      71.6 %), and 926 elderly individuals (60-69, elderly/control group). The
      population-based controls were sampled from the resident registry according to
      the gender ratio of the EL group. We found that the EL group had significantly
      higher levels of LS (30.74 vs. 28.93), PA (3.91 vs. 3.67), and AB (7.89 vs. 7.40)
      and a lower level of NA (1.02 vs. 1.27) than the elderly group. Multivariate
      logistic regression analysis revealed that higher levels of LS, PA, AB, and NA
      were significantly associated with EL, with odds ratios (ORs) of 1.98 (95 % CI,
      1.36-2.89), 2.35 (95 % CI, 1.59-3.48), 2.56 (95 % CI, 1.75-3.75), and 0.50 (95 %
      CI, 0.33-0.74), respectively. Stratification analysis showed that the
      associations were significant in the healthy subsample, with the following ORs:
      LS = 2.31, PA = 2.53, AB = 3.05, and NA = 0.39. In conclusion, SWB, with high
      cognitive and emotional facets, was associated with EL in the healthy Rugao
      population. The findings imply that interventions that aim to improve elderly
      individuals' SWB may promote their quality of life and, ultimately, EL.

PMID- 24590628
TI  - Ginsenoside metabolite compound K stimulates glucagon-like peptide-1 secretion in
      NCI-H716 cells via bile acid receptor activation.
AB  - Compound K (CK) is a major metabolite of ginsenosides that is absorbed. CK has
      antidiabetic effects, although the mechanisms underlying the effects of CK have
      not fully been known. To elucidate the mechanisms underlying the antidiabetic
      effects of CK, we studied the effects of CK on GLP-1 secretion from NCI-H716
      cells, and explored the mechanisms underlying CK-induced GLP-1 secretion.
      Treatment of NCI-H716 cells with 10, 50, and 100 MUM CK significantly increased
      GLP-1 secretion, and intracellular Ca2+ and cAMP levels in a dose-dependent
      manner. Transfection of NCI-H716 cells with siRNA specific to alpha-gustducin and
      siRNA specific to TAS1R3 had no effect on CK-induced GLP-1 secretion and Ca2+
      increase. However, transfection of NCI-H716 cells with TGR5-specific siRNA
      significantly inhibited CK-induced GLP-1 secretion and the increase in Ca2+ and
      cAMP levels. Moreover, CK showed human TGR5 agonist activity in CHO-K1 cells
      transiently transfected with human TGR5. Our data provide a novel mechanism of CK
      for antidiabetic effects. Moreover, the findings might suggest that CK is a
      potential agent that has multiple biological functions in the body via GLP-1
      secretion and TGR5 activation.

PMID- 24590629
TI  - Squaring the circle? On the search for circulating biomarkers in polygenic
      psychiatric disorders.

PMID- 24590630
TI  - Interest towards human, animal and object in children with autism spectrum
      disorders: an ethological approach at home.
AB  - Autistic spectrum disorders (ASD) are characterised by attention deficits in
      communication and social interactions and a lack of interest in people. Data are
      mostly based on clinical situations. However, recent studies have shown a more
      mixed situation where children with ASD (ASD children) displayed interest towards
      humans, in both experimental and natural settings. The aim of this study was to
      assess the interest of ASD children in a natural standardised home setting. Here,
      we hypothesised that ASD children would display more interest towards animate
      stimuli-human and pet-when in the child's home than in the lab experimental
      setting. We used an ethological approach involving observations, a methodological
      alternative to lab static techniques, to investigate the behaviour of ninety 6-
      to 12-year-old ASD and typical development (TD) children. Our results were
      consistent with those of the literature revealing that the ASD children displayed
      interest towards animate stimuli as did children with TD children. Interestingly,
      while the ASD children showed higher interest towards humans, e.g. their parent,
      than the TD children did, they showed less interest towards pet compared to the
      TD children. Our results suggested that animals are not inherently easy to decode
      for ASD children, in contrast with previous experiences where a pet was regarded
      as a more attractive partner, easier to be understood. At last, the ASD children
      changed more frequently their focus point than the TD children did. These
      differences may be explained by the reduced attention skills in ASD or the
      study's context. To conclude, larger exploratory studies in natural settings
      conducted beyond ordinary human to human interactions are crucial for better
      understanding of the underlying mechanisms involved in social interactions in
      ASD. 

PMID- 24590632
TI  - Molecular theory of phase separation in nematic liquid crystals doped with
      spherical nanoparticles.
AB  - A molecular-statistical theory is developed, which enables one to describe the
      nematic-isotropic phase transition in liquid crystals doped with spherical
      nanoparticles taking into account the effects of phase separation. It has been
      shown that in the case of strong interaction between nanoparticles and mesogenic
      molecules the nematic nanocomposite possesses a number of unexpected properties.
      In particular, the nematic-isotropic co-existence region appears to be very
      broad, and the system either undergoes a direct transition from the isotropic
      phase into the phase-separated state, or undergoes the transition into the
      homogeneous nematic phase first and then phase-separates at a lower temperature.
      Phase separation does not occur at all if the concentration of the nanoparticles
      is sufficiently low, and in some cases it takes place only within a finite region
      of nanoparticle concentration. A number of temperature-concentration phase
      diagrams is presented and the molar fractions of nanoparticles in the co-existing
      isotropic and nematic phases are calculated numerically as functions of
      temperature. 

PMID- 24590631
TI  - Alpha-synuclein mRNA expression in oligodendrocytes in MSA.
AB  - Multiple system atrophy (MSA) is a progressive neurodegenerative disease
      presenting clinically with parkinsonian, cerebellar, and autonomic features.
      alpha-Synuclein (alphasyn), encoded by the gene SNCA, is the main constituent of
      glial cytoplasmic inclusion (GCI) found in oligodendrocytes in MSA, but the
      methods of its accumulation have not been established. The aim of this study is
      to investigate alterations in regional and cellular SNCA mRNA expression in MSA
      as a possible substrate for GCI formation. Quantitative reverse transcription
      polymerase chain reaction (qPCR) was performed on postmortem brain samples from
      15 MSA, 5 IPD, and 5 control cases to investigate regional expression in the
      frontal and occipital regions, dorsal putamen, pontine base, and cerebellum. For
      cellular expression analysis, neurons and oligodendrocytes were isolated by laser
      capture microdissection from five MSA and five control cases. SNCA mRNA
      expression was not significantly different between the MSA, IPD and control cases
      in all regions (multilevel model, P = 0.14). After adjusting for group effect,
      the highest expression was found in the occipital cortex while the lowest was in
      the putamen (multilevel model, P < 0.0001). At the cellular level, MSA
      oligodendrocytes expressed more SNCA than control oligodendrocytes and expression
      in MSA neurons was slightly lower than that in controls, however, these results
      did not reach statistical significance. We have demonstrated regional variations
      in SNCA expression, which is higher in cortical than subcortical regions. This
      study is the first to demonstrate SNCA mRNA expression by oligodendrocytes in
      human postmortem tissue using qPCR and, although not statistically significant,
      could suggest that this may be increased in MSA compared to controls.

PMID- 24590633
TI  - The challenges of comparing results between placebo controlled randomized trials
      and non-experimental new user, active comparator cohort studies: the example of
      olmesartan.

PMID- 24590634
TI  - Shifting patterns in the interpretation of phase III clinical trial outcomes in
      advanced non-small-cell lung cancer: the bar is dropping.
AB  - PURPOSE: Despite multiple trials of new agents in advanced non-small-cell lung
      cancer (NSCLC), outcomes remain poor. This study explores how the design and
      interpretation of randomized trials in advanced NSCLC has changed over time.
      METHODS: Phase III randomized controlled trials of systemic therapy for advanced
      NSCLC between 1980 and 2010 were identified, and their primary end point,
      outcome, statistical significance, and conclusions were recorded. RESULTS: Of 245
      trials identified, 203 were eligible for study inclusion. Although overall
      survival remains the most common primary end point of phase III trials, more
      trials from the last decade have used progression-free survival instead (none in
      1980 to 1990, 13% in 2001 to 2010; P = .002). The percentage of trials meeting
      their primary statistical end points remained stable over time; however, the
      percentage of trials reporting a positive outcome without meeting that end point
      increased (30% in 1980 to 1990, 53% in 2001 to 2010; P < .001). A trend toward
      decreasing magnitude of survival gain in positive trials was seen over time (3.9
      months in 1980 to 1990, 2.5 months in 2001 to 2010; P = .11), with a concomitant
      increase in the sample size of clinical trials over the same time period (median:
      152 patients in 1980 to 1990, 413 in 2001 to 2010; P < .001). Only studies
      predating 1990 reported negative results as a result of insufficient magnitude of
      survival benefit despite statistical significance. CONCLUSION: A significant
      shift has occurred over the past three decades in the design and interpretation
      of phase III trials in advanced NSCLC. The use of survival as the primary measure
      of benefit is declining, as is the magnitude of benefit deemed clinically
      relevant.

PMID- 24590635
TI  - Double-blind, placebo-controlled, multicenter, randomized, phase IIb neoadjuvant
      study of letrozole-lapatinib in postmenopausal hormone receptor-positive, human
      epidermal growth factor receptor 2-negative, operable breast cancer.
AB  - PURPOSE: This is a randomized, double-blind, placebo-controlled study aimed to
      evaluate the clinical and biologic effects of letrozole plus lapatinib or placebo
      as neoadjuvant therapy in hormone receptor (HR) -positive/human epidermal growth
      factor receptor 2 (HER2) -negative operable breast cancer. METHODS: Ninety-two
      postmenopausal women with stage II to IIIA primary breast cancer were randomly
      assigned to preoperative therapy consisting of 6 months of letrozole 2.5 mg
      orally daily plus lapatinib 1,500 mg orally daily or placebo. Surgery was
      performed within 2 weeks from the last study medication. Clinical response was
      assessed by ultrasonography. Pre- and post-treatment samples were evaluated for
      selected biomarkers. Fresh-frozen tissue samples were collected for genomic
      analyses. RESULTS: Numerically similar clinical response rates (partial +
      complete response) were observed (70% for letrozole-lapatinib and 63% for
      letrozole-placebo). Toxicities were generally mild and manageable. A significant
      decrease in Ki-67 and pAKT expression from baseline to surgery was observed in
      both arms. Overall, 34 patients (37%) had a mutation in PIK3CA exon 9 or 20. In
      the letrozole-lapatinib arm, the probability of achieving a clinical response was
      significantly higher in the presence of PIK3CA mutation (objective response rate,
      93% v 63% in PIK3CA wild type; P = .040). CONCLUSION: The combination of
      letrozole-lapatinib in early breast cancer was feasible, with expected and
      manageable toxicities. In unselected estrogen receptor-positive/HER2-negative
      patients, letrozole-lapatinib and letrozole-placebo resulted in a similar overall
      clinical response rate and similar effect on Ki-67 and pAKT. Our secondary end
      point findings of a significant correlation between PIK3CA mutation and response
      to letrozole-lapatinib in HR-positive/HER2-negative early breast cancer must now
      be independently confirmed.

PMID- 24590636
TI  - Randomized, controlled trial of yoga in women with breast cancer undergoing
      radiotherapy.
AB  - PURPOSE: Previous research incorporating yoga (YG) into radiotherapy (XRT) for
      women with breast cancer finds improved quality of life (QOL). However,
      shortcomings in this research limit the findings. PATIENTS AND METHODS: Patients
      with stages 0 to III breast cancer were recruited before starting XRT and were
      randomly assigned to YG (n = 53) or stretching (ST; n = 56) three times a week
      for 6 weeks during XRT or waitlist (WL; n = 54) control. Self-report measures of
      QOL (Medical Outcomes Study 36-item short-form survey; primary outcomes),
      fatigue, depression, and sleep quality, and five saliva samples per day for 3
      consecutive days were collected at baseline, end of treatment, and 1, 3, and 6
      months later. RESULTS: The YG group had significantly greater increases in
      physical component scale scores compared with the WL group at 1 and 3 months
      after XRT (P = .01 and P = .01). At 1, 3, and 6 months, the YG group had greater
      increases in physical functioning compared with both ST and WL groups (P < .05),
      with ST and WL differences at only 3 months (P < .02). The group differences were
      similar for general health reports. By the end of XRT, the YG and ST groups also
      had a reduction in fatigue (P < .05). There were no group differences for mental
      health and sleep quality. Cortisol slope was steepest for the YG group compared
      with the ST and WL groups at the end (P = .023 and P = .008) and 1 month after
      XRT (P = .05 and P = .04). CONCLUSION: YG improved QOL and physiological changes
      associated with XRT beyond the benefits of simple ST exercises, and these
      benefits appear to have long-term durability.

PMID- 24590638
TI  - Metastatic lobular breast carcinoma mimicking primary signet ring adenocarcinoma
      in a patient with a suspected CDH1 mutation.

PMID- 24590637
TI  - Survival, durable tumor remission, and long-term safety in patients with advanced
      melanoma receiving nivolumab.
AB  - PURPOSE: Programmed cell death 1 (PD-1) is an inhibitory receptor expressed by
      activated T cells that downmodulates effector functions and limits the generation
      of immune memory. PD-1 blockade can mediate tumor regression in a substantial
      proportion of patients with melanoma, but it is not known whether this is
      associated with extended survival or maintenance of response after treatment is
      discontinued. PATIENTS AND METHODS: Patients with advanced melanoma (N = 107)
      enrolled between 2008 and 2012 received intravenous nivolumab in an outpatient
      setting every 2 weeks for up to 96 weeks and were observed for overall survival,
      long-term safety, and response duration after treatment discontinuation. RESULTS:
      Median overall survival in nivolumab-treated patients (62% with two to five prior
      systemic therapies) was 16.8 months, and 1- and 2-year survival rates were 62%
      and 43%, respectively. Among 33 patients with objective tumor regressions (31%),
      the Kaplan-Meier estimated median response duration was 2 years. Seventeen
      patients discontinued therapy for reasons other than disease progression, and 12
      (71%) of 17 maintained responses off-therapy for at least 16 weeks (range, 16 to
      56+ weeks). Objective response and toxicity rates were similar to those reported
      previously; in an extended analysis of all 306 patients treated on this trial
      (including those with other cancer types), exposure-adjusted toxicity rates were
      not cumulative. CONCLUSION: Overall survival following nivolumab treatment in
      patients with advanced treatment-refractory melanoma compares favorably with that
      in literature studies of similar patient populations. Responses were durable and
      persisted after drug discontinuation. Long-term safety was acceptable. Ongoing
      randomized clinical trials will further assess the impact of nivolumab therapy on
      overall survival in patients with metastatic melanoma.

PMID- 24590639
TI  - The Kafkaesque process of cancer diagnosis.

PMID- 24590640
TI  - Genetic biomarkers for Fluorouracil toxicity prediction: the long road to
      clinical utility.

PMID- 24590641
TI  - Cisplatin-based chemotherapy and the risk of solid tumors in patients with
      testicular nonseminoma: still a matter of debate.

PMID- 24590642
TI  - Cost effectiveness and cancer drugs.

PMID- 24590643
TI  - Reply to G. Gandaglia et al.

PMID- 24590645
TI  - Estrogen receptor and receptor tyrosine kinase signaling: use of combinatorial
      hormone and epidermal growth factor receptor/human epidermal growth factor
      receptor 2-targeted therapies for breast cancer.

PMID- 24590646
TI  - Fellowship engagement in hematology/oncology professionalism training.

PMID- 24590644
TI  - Randomized controlled trial of early zoledronic acid in men with castration
      sensitive prostate cancer and bone metastases: results of CALGB 90202 (alliance).
AB  - PURPOSE: Zoledronic acid decreases the risk for skeletal-related events (SREs) in
      men with castration-resistant prostate cancer and bone metastases but its role
      earlier in the natural history of the disease is unknown. This phase III study
      evaluated the efficacy and safety of earlier treatment with zoledronic acid in
      men with castration-sensitive metastatic prostate cancer. PATIENTS AND METHODS:
      Men with castration-sensitive prostate cancer and bone metastases whose androgen
      deprivation therapy was initiated within 6 months of study entry were randomly
      assigned in a blinded 1:1 ratio to receive zoledronic acid (4 mg intravenously
      every 4 weeks) or a placebo. After their disease progressed to castration
      resistant status, all patients received open-label treatment with zoledronic
      acid. The primary end point was time to first SRE, defined as radiation to bone,
      clinical fracture, spinal cord compression, surgery to bone, or death as a result
      of prostate cancer. Target accrual was 680 patients. Primary analysis was planned
      after 470 SREs. The study was discontinued prematurely (645 patients; 299 SREs)
      after the corporate supporter withdrew study drug supply. RESULTS: Early
      zoledronic acid was not associated with increased time to first SRE. The median
      time to first SRE was 31.9 months in the zoledronic acid group (95% CI, 24.2 to
      40.3) and 29.8 months in the placebo group (95% CI, 25.3 to 37.2; hazard ratio,
      0.97; 95% CI, 0 to 1.17; one-sided stratified log-rank P = .39). Overall survival
      was similar between the groups (hazard ratio, 0.88; 95% CI, 0.70 to 1.12; P =
      .29). Rates of adverse events were similar between the groups. CONCLUSION: In men
      with castration-sensitive prostate cancer and bone metastases, early treatment
      with zoledronic acid was not associated with lower risk for SREs.

PMID- 24590648
TI  - Reply to J.E. Battley et al.

PMID- 24590647
TI  - Wide local excision of perianal mucinous adenocarcinoma.

PMID- 24590649
TI  - Role of human papillomavirus and p16 staining in a patient with head and neck
      cancer presenting with a synchronous lung nodule: a case report and review of the
      literature.

PMID- 24590650
TI  - What is your gut feeling about opioid rotation?

PMID- 24590651
TI  - To treat or not to treat, that is the question: the role of bone-targeted therapy
      in metastatic prostate cancer.
AB  - The Oncology Grand Rounds series is designed to place original reports published
      in the Journal into clinical context. A case presentation is followed by a
      description of diagnostic and management challenges, a review of the relevant
      literature, and a summary of the authors' suggested management approaches. The
      goal of this series is to help readers better understand how to apply the results
      of key studies, including those published in Journal of Clinical Oncology, to
      patients seen in their own clinical practice. A 62-year-old construction site
      manager experienced 6 weeks of back pain that was not responsive to over-the
      counter nonsteroidal anti-inflammatory medications. He visited his wife's primary
      care physician for evaluation. He denied neurologic symptoms or worsening of pain
      while lying down. He smoked (30 pack-years, quit 4 years ago), and drinks 3 beers
      each evening and more on weekends (up to a six-pack). He has had two lower
      extremity fractures from falls at construction sites. At the time of the physical
      examination, he was 5 feet 11 inches tall and weighed 194 pounds. He was alert,
      oriented, and in mild distress. He had no percussion tenderness of his spine, and
      a neurologic examination was negative. A digital rectal examination revealed an
      enlarged prostate with an area of induration of the left, normal rectal tone, and
      guaiac-negative stool. Laboratory studies included normal blood counts,
      electrolytes, and renal and liver function tests (including lactic acid
      dehydrogenase and total protein). The prostate-specific antigen (PSA) was 114
      ng/mL; he had no prior PSA test. A bone scan showed diffuse bony involvement
      including the T7 vertebral body and left pedicle, ribs, pelvis, and calvarium.
      Magnetic resonance imaging of his spine confirmed bone metastases but showed no
      evidence of extension into the epidural space or spinal cord compromise. A
      prostate biopsy revealed Gleason 4+4 adenocarcinoma of the prostate. Androgen
      deprivation therapy with leuprolide acetate was initiated, and the addition of a
      bone-targeted agent was considered. 

PMID- 24590652
TI  - Uterine inflammatory myofibroblastic tumor in a 10-year-old girl presenting as
      polypoid mass.

PMID- 24590653
TI  - Neuroblastoma mRNAs predict outcome in children with stage 4 neuroblastoma: a
      European HR-NBL1/SIOPEN study.
AB  - PURPOSE: To evaluate the hypothesis that detection of neuroblastoma mRNAs by
      reverse transcriptase quantitative polymerase chain reaction (RTqPCR) in
      peripheral blood (PB) and bone marrow aspirates (BM) from children with stage 4
      neuroblastoma are clinically useful biomarkers of risk. METHODS: RTqPCR for
      paired-like homeobox 2b (PHOX2B), tyrosine hydroxylase (TH), and doublecortin
      (DCX) mRNA in PB and BM of children enrolled onto the High-Risk Neuroblastoma
      Trial-1 of the European Society of Pediatric Oncology Neuroblastoma Group (HR
      NBL1/SIOPEN) was performed at diagnosis and after induction therapy. RESULTS:
      High levels of TH, PHOX2B, or DCX mRNA in PB or BM at diagnosis strongly
      predicted for worse event-free survival (EFS) and overall survival (OS) in a
      cohort of 290 children. After induction therapy, high levels of these mRNAs
      predicted worse EFS and OS in BM but not in PB. Combinations of mRNAs in BM did
      not add to the predictive power of any single mRNA. However, in the original (n =
      182) and validation (n = 137) PB cohorts, high TH (log10TH > 0.8) or high PHOX2B
      (log10PHOX2B > 0.28) identify 19% of children as ultrahigh risk, with 5-year EFS
      and OS rates of 0%; OS rate was 25% (95% CI, 16% to 36%) and EFS rate was 38%
      (95% CI, 28% to 49%) in the remaining children. The magnitude of reduction in
      mRNA level between diagnosis and postinduction therapy in BM or PB was not of
      additional predictive value. CONCLUSION: High levels of TH and PHOX2B mRNA in PB
      at diagnosis objectively identify children with ultrahigh-risk disease who may
      benefit from novel treatment approaches. The level of TH, PHOX2B, and DCX mRNA in
      BM and/or PB at diagnosis might contribute to an algorithm to improve
      stratification of children for treatment.

PMID- 24590655
TI  - Nivolumab: promising survival signal coupled with limited toxicity raises
      expectations.

PMID- 24590656
TI  - CO(2) concentration in day care centres is related to wheezing in attending
      children.
AB  - Poor ventilation at day care centres (DCCs) was already reported, although its
      effects on attending children are not clear. This study aimed to evaluate the
      association between wheezing in children and indoor CO2 (a ventilation surrogate
      marker) in DCC and to identify behaviours and building characteristics
      potentially related to CO2. In phase I, 45 DCCs from Lisbon and Oporto (Portugal)
      were selected through a proportional stratified random sampling. In phase II, 3
      months later, 19 DCCs were further reassessed after cluster analysis for the
      greatest difference comparison. In both phases, children's respiratory health was
      assessed by ISAAC-derived questionnaires. Indoor CO2 concentrations and building
      characteristics of the DCC were evaluated in both phases, using complementary
      methods. Mixed effect models were used to analyze the data. In phase I, which
      included 3,186 children (mean age 3.1 +/- 1.5 years), indoor CO2 concentration in
      the DCC rooms was associated with reported wheezing in the past 12 months (27.5
      %) (adjusted odds ratio (OR) for each increase of 200 ppm 1.04, 95 % CI 1:01 to
      1:07). In phase II, the association in the subsample of 1,196 children seen in 19
      out of the initial 45 DCCs was not significant (adjusted OR 1.02, 95 % CI 0.96 to
      1.08). Indoor CO2 concentration was inversely associated with the practices of
      opening windows and internal doors and with higher wind velocity. A positive
      trend was observed between CO2 and prevalence of reported asthma (4.7 %).
      CONCLUSION: Improved ventilation is needed to achieve a healthier indoor
      environment in DCC.

PMID- 24590654
TI  - Genetic markers of toxicity from capecitabine and other fluorouracil-based
      regimens: investigation in the QUASAR2 study, systematic review, and meta
      analysis.
AB  - PURPOSE: Fluourouracil (FU) is a mainstay of chemotherapy, although toxicities
      are common. Genetic biomarkers have been used to predict these adverse events,
      but their utility is uncertain. PATIENTS AND METHODS: We tested candidate
      polymorphisms identified from a systematic literature search for associations
      with capecitabine toxicity in 927 patients with colorectal cancer in the Quick
      and Simple and Reliable trial (QUASAR2). We then performed meta-analysis of
      QUASAR2 and 16 published studies (n = 4,855 patients) to examine the
      polymorphisms in various FU monotherapy and combination therapy regimens.
      RESULTS: Global capecitabine toxicity (grades 0/1/2 v grades 3/4/5) was
      associated with the rare, functional DPYD alleles 2846T>A and *2A (combined odds
      ratio, 5.51; P = .0013) and with the common TYMS polymorphisms 5'VNTR2R/3R and
      3'UTR 6bp ins-del (combined odds ratio, 1.31; P = 9.4 * 10(-6)). There was weaker
      evidence that these polymorphisms predict toxicity from bolus and infusional FU
      monotherapy. No good evidence of association with toxicity was found for the
      remaining polymorphisms, including several currently included in predictive kits.
      No polymorphisms were associated with toxicity in combination regimens.
      CONCLUSION: A panel of genetic biomarkers for capecitabine monotherapy toxicity
      would currently comprise only the four DPYD and TYMS variants above. We estimate
      this test could provide 26% sensitivity, 86% specificity, and 49% positive
      predictive value-better than most available commercial kits, but suboptimal for
      clinical use. The test panel might be extended to include additional, rare DPYD
      variants functionally equivalent to *2A and 2846A, though insufficient evidence
      supports its use in bolus, infusional, or combination FU. There remains a need to
      identify further markers of FU toxicity for all regimens.

PMID- 24590657
TI  - Human bocaviruses are commonly found in stools of hospitalized children without
      causal association to acute gastroenteritis.
AB  - Human bocaviruses (HBoVs) may be grouped into respiratory (HBoV1) and enteric
      (HBoV2-4) types. We examined this association of HBoV types and clinical symptoms
      in 955 children who had acute gastroenteritis (AGE, n = 172), acute respiratory
      tract infection (ARTI, n = 545) or symptoms of both (n = 238). Both nasal swab
      and stool specimens were studied for such patients. HBoV1 DNA was detected in 6.2
      % of patients with ARTI and 9.2 % of patients with symptoms of both ARTI and AGE,
      but in only 1.7 % of patients with AGE alone. In about one half of the cases,
      HBoV1 was detected concomitantly in nasal swab and stool samples. HBoV2 was found
      in stool samples of patients with AGE (5.8 %), ARTI (5.1 %) and symptoms of both
      (5.5 %) but only rarely in nasal swabs. HBoV3 was found in the stools, but not in
      nasal swabs, in 0.6, 1.1 and 0.8 % of patients with, respectively, AGE, ARTI and
      both. HBoV4 was not found. All but one HBoV-positive stool sample of AGE patients
      contained a known gastroenteritis virus (rotavirus, norovirus, sapovirus,
      astrovirus or enteric adenovirus) that was probably responsible for the symptoms
      of the respective case. Sera of 30 HBoV-positive patients were available, and IgM
      antibodies for HBoVs were found in ten cases and HBoV DNA in eight of these.
      CONCLUSIONS: HBoV2 and HBoV3 were more commonly found in stool than in nasal swab
      samples, but the findings could not be causally linked with AGE. HBoV1 was
      commonly found in stool samples during ARTI, with or without gastrointestinal
      symptoms.

PMID- 24590658
TI  - Wavelet analysis of quadriceps power spectra and amplitude under varying levels
      of contraction intensity and velocity.
AB  - INTRODUCTION: We investigated the effect of contraction intensity [100%, 75%,
      50%, and 25% maximum voluntary contraction (MVC)] and movement velocity (50
      degrees , 100 degrees , 200 degrees , and 400 degrees /s) on surface
      electromyography root mean square amplitude (SEMGRMS ) and median frequency
      (SEMGMDF ) of rectus femoris (RF), vastus lateralis (VL), and vastus medialis
      (VM). METHODS: SEMGs during knee extension were resolved into their respective
      frequencies using wavelet transformations. RESULTS: RF, VL, and VM muscles
      displayed increased SEMGMDF as contraction intensity increased from 25% to 50%
      MVC and from 75% to 100% MVC, and each muscle displayed its own unique frequency
      shifting patterns. The SEMGMDF was not influenced by movement velocity. SEMGRMS
      increased in all 3 muscles as contraction intensity increased and was influenced
      by movement velocity, with the highest values observed at 400 degrees  and 200
      degrees /s. CONCLUSIONS: We infer that increasing contraction intensity
      facilitates greater recruitment of fast-twitch muscle fibers, but there are
      differing responses in RF, VL, and VM muscles.

PMID- 24590659
TI  - Copper-catalyzed site-selective intramolecular amidation of unactivated C(sp3)-H
      bonds.
AB  - The intramolecular dehydrogenative amidation of aliphatic amides, directed by a
      bidentate ligand, was developed using a copper-catalyzed sp(3) C-H bond
      functionalization process. The reaction favors predominantly the C-H bonds of
      beta-methyl groups over the unactivated methylene C-H bonds. Moreover, a
      preference for activating sp(3) C-H bonds of beta-methyl groups, via a five
      membered ring intermediate, over the aromatic sp(2) C-H bonds was also observed
      in the cyclometalation step. Additionally, sp(3) C-H bonds of unactivated
      secondary sp(3) C-H bonds could be functionalized by favoring the ring carbon
      atoms over the linear carbon atoms.

PMID- 24590661
TI  - Torpedo formation and Purkinje cell loss: modeling their relationship in
      cerebellar disease.
AB  - Torpedo formation and Purkinje cell (PC) loss represent standard and inter
      related cerebellar responses to injury. Surprisingly, the nature of their
      relationship has not been carefully characterized across a range of normal and
      disease states. Are brains with more torpedoes expected to have fewer PCs? We
      quantified torpedoes and PCs in four groups: essential tremor (ET),
      spinocerebellar ataxia (SCA), multiple system atrophy-cerebellar (MSA-C), and
      controls. Brains from 100 individuals (58 ET, 27 controls, 7 SCA, 8 MSA-C) were
      available at the New York Brain Bank. After complete neuropathological
      assessment, a standard parasagittal neocerebellar block was harvested; a 7-MUm
      thick section was stained with Luxol fast blue/hematoxylin and eosin; and
      torpedoes and PCs were quantified. For a given PC count, SCA and MSA-C cases
      often had higher torpedo counts than ET cases or controls. Furthermore, the
      relationship between torpedo and PC counts was complex. The correlation between
      torpedo and PC counts was negative in ET cases (i.e., individuals with more
      torpedoes had fewer PCs [i.e., more PC loss]) whereas the relationship was
      positive in MSA-C cases (i.e., individuals with fewer PCs [i.e., more PC loss]
      had fewer torpedoes). Patients with SCA showed both patterns. When all diagnostic
      groups were combined, the correlation was best fit by a quadratic (i.e.,
      parabolic) model rather than a simple linear model; this model incorporated data
      on the negative correlation in ET cases, the mixed results in SCA cases, and the
      positive correlation in MSA-C cases (r = 0.636). The relationship between torpedo
      and PC counts was complex and heterogeneous across a range of cerebellar disease
      states, and was best characterized by a quadratic rather than a simple model.
      With more severe cerebellar disease, torpedoes can be quite numerous and are
      likely a common feature of surviving PCs, but eventually, dramatic loss of PC
      leads to a paradoxical reduction in observable torpedoes.

PMID- 24590660
TI  - The contribution of extrasynaptic signaling to cerebellar information processing.
AB  - The diversity of synapses within the simple modular structure of the cerebellum
      has been crucial for study of the phasic extrasynaptic signaling by fast
      neurotransmitters collectively referred to as "spillover." Additionally, the
      accessibility of cerebellar components for in vivo recordings and their
      recruitment by simple behaviors or sensory stimuli has allowed for both direct
      and indirect demonstrations of the effects of transmitter spillover in the intact
      brain. The continued study of spillover in the cerebellum not only promotes our
      understanding of information transfer through cerebellar structures but also how
      extrasynaptic signaling may be regulated and interpreted throughout the CNS. 

PMID- 24590662
TI  - Correlates of urban children's leisure-time physical activity and sedentary
      behaviors during school days.
AB  - OBJECTIVES: Understanding correlates of physical activity and sedentary behaviors
      may contribute to fostering active lifestyles. This study aimed to identify
      correlates of physical activity and sedentary behaviors in leisure-time among
      Portuguese urban children, during school days. METHODS: A cross-sectional survey
      was conducted with 802 students (416 boys), aged 10-12 years. A questionnaire was
      used to collect data of physical activity, sedentary behaviors, psychological and
      behavioral variables related to physical activity and sedentary behaviors.
      Analyses were run separately for boys and girls. RESULTS: Television viewing
      occupied the most leisure-time of boys and girls, followed by computer usage, and
      video game playing. These behaviors occupied 259.7 min/day for boys and 208.6 for
      girls (P = 0.002). Reported moderate-to-vigorous physical activity was 23.7 min
      for boys and 12.8 min for girls (P < 0.001). Perception of competence and
      academic achievement were related to physical activity for the boys and girls.
      Computer use and playing video games with friends were only related to physical
      activity for the boys. On the other hand, parents' physical activity
      participation was related with boys' and girls' physical activity. The correlates
      of sedentary behavior were outdoor play for the boys, age for the girls, and
      playing video games with friends for both. CONCLUSIONS: This finding suggests
      that interventions should be considered to replace joint video game time with
      joint physical activity time.

PMID- 24590664
TI  - Causes of death in preweaned northern elephant seal pups (Mirounga
      angustirostris, Gill, 1866), Ano Nuevo State Reserve, California, 2012.
AB  - During an ongoing physiological ecology study on pups and adult female northern
      elephant seals (Mirounga angustirostris, Gill, 1866) on the mainland rookery at
      Ano Nuevo State Reserve (California), an opportunity was afforded to collect
      fresh dead pups for parasitology and necropsy. The investigation was undertaken
      to delineate the causes of death of northern elephant seals recovered from Ano
      Nuevo State Reserve. Prior to this study, there was no evidence of increased
      mortality or health problems on this rookery. Necropsies, histology, and
      ancillary diagnostic studies were conducted on 21 fresh dead preweaned pups. Ages
      ranged from 1 stillbirth to pups approximately 2 weeks of age. Gross lesions
      included varying degrees of bruising, hemorrhage, lacerations, and fractures
      attributed to blunt force trauma to the head, chest, and/or abdomen in 16 pups;
      starvation in 6 pups; bite wounds in 2 pups; generalized icterus in 2 pups;
      presumptive drowning in 2 pups; and 1 stillbirth. Most pups had multiple gross
      lesions. Following light microscopic examination, pups could be assigned into 4
      general diagnostic categories: 1) trauma, 2) nutritional status, 3) infectious
      conditions, and 4) congenital anomalies. This investigation of preweaned pup
      mortality of northern elephant seals in California further refines diagnostic
      categories for perinatal pup mortality. 

PMID- 24590663
TI  - Role of lithium augmentation in the management of major depressive disorder.
AB  - The high rate of non-responders to initial treatment with antidepressants
      requires subsequent treatment strategies such as augmentation of antidepressants.
      Clinical guidelines recommend lithium augmentation as a first-line treatment
      strategy for non-responding depressed patients. The objectives of this review
      were to discuss the current place of lithium augmentation in the management of
      treatment-resistant depression and to review novel findings concerning lithium's
      mechanisms of action. We conducted a comprehensive and critical review of
      randomized, placebo-controlled trials, controlled and naturalistic comparator
      studies, and continuation-phase and discontinuation studies of lithium
      augmentation in major depression. The outcomes of interest were efficacy, factors
      allowing outcome prediction and results from preclinical studies investigating
      molecular mechanisms of lithium action. Substantial efficacy of lithium
      augmentation in the acute treatment of major depression has been demonstrated in
      more than 30 open-label studies and 10 placebo-controlled trials. In a meta
      analysis addressing the efficacy of lithium in 10 randomized, controlled trials,
      it had a significant positive effect versus placebo, with an odds ratio of 3.11
      corresponding to a number-needed-to-treat (NNT) of 5 and a mean response rate of
      41.2% (versus 14.4% in the placebo group). The main limitations of these studies
      were the relatively small numbers of study participants and the fact that most
      studies included augmentation of tricyclic antidepressants, which are not in
      widespread use anymore. Evidence from continuation-phase studies is sparse but
      suggests that lithium augmentation should be maintained in the lithium
      antidepressant combination for at least 1 year to prevent early relapses.
      Concerning outcome prediction, single studies have reported associations of
      better outcome rates with more severe depressive symptomatology, significant
      weight loss, psychomotor retardation, a history of more than three major
      depressive episodes and a family history of major depression. Additionally, one
      study suggested a predictive role of the -50T/C single nucleotide polymorphism of
      the glycogen synthase kinase 3 beta (GSK3B) gene in the probability of response
      to lithium augmentation. With regard to novel mechanisms of action, GABAergic,
      neurotrophic and genetic effects might explain the effects of lithium
      augmentation. In conclusion, augmentation of antidepressants with lithium remains
      a first-line, evidence-based management option for patients with major depression
      who have not responded adequately to antidepressants. While the mechanisms of
      action are currently widely studied, further clinical research on the role of
      lithium potentiation of the current generation of antidepressants is warranted to
      reinforce its role as a gold-standard treatment for patients who respond
      inadequately to antidepressants.

PMID- 24590665
TI  - An evaluation of serotyping of Avibacterium paragallinarum by use of a multiplex
      polymerase chain reaction.
AB  - In the present study, the ability of a recently proposed multiplex polymerase
      chain reaction (mPCR) to determine the serogroups (A, B, and C) of Avibacterium
      paragallinarum was evaluated. A total of 12 reference strains and 69 field
      isolates of Av. paragallinarum from Ecuador, Mexico, Panama, and Peru were
      included in the study. With some exceptions (which were serotyped in the current
      study), all of the isolates and strains had been previously examined by 2
      serotyping schemes (Page and Kume) or were the formal reference strains for the
      schemes. Three of 6 (50%) reference strains of serogroup A, 2 (100%) of serogroup
      B, and 1 of 4 (25%) reference strains of serogroup C were correctly serotyped by
      the mPCR. With the field isolates, the mPCR correctly recognized 16 of the 17
      serogroup A isolates, 10 of the 12 serogroup B isolates, and 18 of the 37
      serogroup C isolates. Overall, the specificity and sensitivity of the PCR test
      was as follows: 82.6% and 87.3% (serogroup A), 85.7% and 71.9% (serogroup B), and
      46.3% and 100% (serogroup C). The poor performance of the mPCR in terms of
      recognition of serogroup C isolates (low sensitivity of 46.3%) and the relatively
      high level of uncertainty about the accuracy of the serogroup A and B results
      (specificity of 87.3% and 71.9%, respectively) means that the assay cannot be
      recommended as a replacement for conventional serotyping. 

PMID- 24590666
TI  - Characterization of Fusobacterium isolates from the respiratory tract of white
      tailed deer (Odocoileus virginianus).
AB  - A total of 23 clinical isolates of Fusobacterium spp. were recovered at necropsy
      over a 2-year period from the respiratory tract of white-tailed deer (Odocoileus
      virginianus). Isolates were identified as Fusobacterium varium (18/23),
      Fusobacterium necrophorum subsp. funduliforme (3/23), and Fusobacterium
      necrophorum subsp. necrophorum (2/23). Using polymerase chain reaction-based
      detection of virulence genes, all F. necrophorum isolates were positive for the
      promoter region of the leukotoxin operon and the hemagglutinin-related protein
      gene, while all F. varium isolates were negative. The presence of the leukotoxin
      gene in F. necrophorum isolates and the absence of this gene in F. varium
      isolates were confirmed by Southern hybridization using 2 separate probes.
      Toxicity to bovine polymorphonuclear leukocytes was observed with all F.
      necrophorum isolates, but was not observed in any F. varium isolates.
      Susceptibility to antimicrobials was markedly different for F. varium as compared
      to F. necrophorum. In summary, no evidence of leukotoxin production was detected
      in any of the 23 F. varium isolates used in the current study. The data suggests
      that F. varium, the most common species isolated, may be a significant pathogen
      in deer with a different virulence mechanism than F. necrophorum. 

PMID- 24590667
TI  - Development of a new real-time polymerase chain reaction assay to detect Duck
      adenovirus A DNA and application to samples from Swiss poultry flocks.
AB  - Between 2008 and 2012, commercial Swiss layer and layer breeder flocks
      experiencing problems in laying performance were sampled and tested for infection
      with Duck adenovirus A (DAdV-A; previously known as Egg drop syndrome 1976
      virus). Organ samples from birds sent for necropsy as well as blood samples from
      living animals originating from the same flocks were analyzed. To detect virus
      specific DNA, a newly developed quantitative real-time polymerase chain reaction
      method was applied, and the presence of antibodies against DAdV-A was tested
      using a commercially available enzyme-linked immunosorbent assay. In 5 out of 7
      investigated flocks, viral DNA was detected in tissues. In addition, antibodies
      against DAdV-A were detected in all of the flocks. 

PMID- 24590668
TI  - Successful transradial retrieval of an embolized guidewire during transradial
      vascular access.
AB  - Transradial catheterization is associated with lower complication rates; however
      limited information is available regarding techniques to overcome unusual
      complications. We present a case of a 58-year-old male with suspected non-ST
      elevated myocardial infarction who underwent transradial coronary angiography
      complicated by guidewire embolization into the radial artery and subsequent
      access loss. Successful retrieval of the embolized guidewire was achieved by re
      accessing the same radial artery and the use of a 2 mm gooseneck microsnare. This
      technique was safe and prevented the need for surgical intervention or femoral
      access for retrieval, which are commonly described in the literature and can
      result in additional complications.

PMID- 24590669
TI  - Functional corannulene: diverse structures, enhanced charge transport, and
      tunable optoelectronic properties.
AB  - Chemical functionalization of various hydrocarbons, such as coronene,
      corannulene, and so forth, shows good promise in electronics applications because
      of their tunable optoelectronic properties. By using quantum chemical
      calculations, we have investigated the changes in the corannulene buckybowl
      structure, which greatly affect its electronic and optical properties when
      functionalized with different electron-withdrawing imide groups. We find that the
      chemical nature and position of functional groups strongly regulate the stacking
      geometry, pi-stacking interactions, and electronic structure. Herein, a range of
      optoelectronic properties and structure-property relationships of various imide
      functionalized corannulenes are explored and rationalized in detail. In terms of
      carrier mobility, we find that the functionalization strongly affects the
      reorganization energy of corannulene, while the enhanced stacking improves
      hopping integrals, favoring the carrier mobility of crystals of
      pentafluorophenylcorannulene-5-monoimide. The study shows a host of emerging
      optoelectronic properties and enhancements in the charge-transport
      characteristics of functionalized corannulene, which may find possible
      semiconductor and electronics applications. 

PMID- 24590671
TI  - Ytterbium(III) porpholactones: beta-lactonization of porphyrin ligands enhances
      sensitization efficiency of lanthanide near-infrared luminescence.
AB  - The near-infrared (NIR) luminescence efficiency of lanthanide complexes is
      largely dependent on the electronic and photophysical properties of antenna
      ligands. Although porphyrin ligands are efficient sensitizers of lanthanide NIR
      luminescence, non-pyrrolic porphyrin analogues, which have unusual symmetry and
      electronic states, have been much less studied. In this work, we used
      porpholactones, a class of beta-pyrrolic-modified porphyrins, as ligands and
      investigated the photophysical properties of lanthanide porpholactones Yb-1 a-5
      a. Compared with Yb porphyrin complexes, the porpholactone complexes displayed
      remarkable enhancement of NIR emission (50-120 %). Estimating the triplet-state
      levels of porphyrin and porpholactone in Gd complexes revealed that beta
      lactonization of porphyrinic ligands lowers the ligand T1 state and results in a
      narrow energy gap between this state and the lowest excited state of Yb(3+) .
      Transient absorption spectra showed that Yb(III) porpholactone has a longer
      transient decay lifetime at the Soret band than the porphyrin analogue (30.8
      versus 17.0 MUs). Thus, the narrower energy gap and longer lifetime arising from
      beta-lactonization are assumed to enhance NIR emission of Yb porpholactones. To
      demonstrate the potential applications of Yb porpholactone, a water-soluble Yb
      bioprobe was constructed by conjugating glucose to Yb-1 a. Interestingly, the NIR
      emission of this Yb porpholactone could be specifically switched on in the
      presence of glucose oxidase and then switched off by addition of glucose. This is
      the first demonstration that non-pyrrolic porphyrin ligands enhance the
      sensitization efficiency of lanthanide luminescence and also display switchable
      NIR emission in the region of biological analytes (800-1400 nm). 

PMID- 24590670
TI  - Comparison of the intrinsic dynamics of aminoacyl-tRNA synthetases.
AB  - Aminoacyl-tRNA synthetases (AARSs) are an important family of enzymes that
      catalyze tRNA aminoacylation reaction (Ibba and Soll in Annu Rev Biochem 2000,
      69:617-650) [1]. AARSs are grouped into two broad classes (class I and II) based
      on sequence/structural homology and mode of their interactions with the tRNA
      molecule (Ibba and Soll in Annu Rev Biochem 2000, 69:617-650) [1]. As protein
      dynamics play an important role in enzyme function, we explored the intrinsic
      dynamics of these enzymes using normal mode analysis and investigated if the two
      classes and six subclasses (Ia-c and IIa-c) of AARSs exhibit any distinct
      patterns of motion. The present study found that the intrinsic dynamics-based
      classification of these enzymes is similar to that obtained based on
      sequence/structural homology for most enzymes. However, the classification of
      seryl-tRNA synthetase was not straightforward; the internal mobility patterns of
      this enzyme are comparable to both IIa and IIb AARSs. This study revealed only a
      few general mobility patterns in these enzymes--(1) the insertion domain is
      generally engaged in anticorrelated motion with respect to the catalytic domain
      for both classes of AARSs and (2) anticodon binding domain dynamics are partly
      correlated and partly anticorrelated with respect to other domains for class I
      enzymes. In most of the class II AARSs, the anticodon binding domain is
      predominately engaged in anticorrelated motion with respect to the catalytic
      domain and correlated to the insertion domain. This study supports the notion
      that dynamic-based classification could be useful for functional classification
      of proteins.

PMID- 24590672
TI  - Types of intraocular lenses for cataract surgery in eyes with uveitis.
AB  - BACKGROUND: Cataract formation often occurs in people with uveitis. It is unclear
      which intraocular lens (IOL) type is optimal for use in cataract surgery for eyes
      with uveitis. OBJECTIVES: To summarize the effects of different IOLs on visual
      acuity, other visual outcomes, and quality of life in people with uveitis. SEARCH
      METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Group
      Trials Register) (The Cochrane Library 2013, Issue 7), Ovid MEDLINE, Ovid MEDLINE
      In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE
      (January 1946 to August 2013), EMBASE (January 1980 to August 2013), Latin
      American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to
      August 2013), the metaRegister of Controlled Trials (mRCT) (www.controlled
      trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO
      International Clinical Trials Registry Platform (ICTRP)
      (www.who.int/ictrp/search/en). We did not use any date or language restrictions
      in the electronic searches for trials. We last searched the electronic databases
      on 14 August 2013. We also performed forward and backward searching using the
      Science Citation Index and the reference lists of the included studies,
      respectively, in August 2013. SELECTION CRITERIA: We included randomized
      controlled trials (RCTs) comparing hydrophobic or hydrophilic acrylic, silicone,
      or poly(methyl methacrylate) (PMMA) IOLs with or without heparin-surface
      modification (HSM), with each other, or with no treatment in adults with uveitis,
      for any indication, undergoing cataract surgery. DATA COLLECTION AND ANALYSIS: We
      used standard methodological procedures expected by The Cochrane Collaboration.
      Two review authors screened the search results and for included studies, assessed
      the risk of bias and extracted data independently. We contacted study
      investigators for additional information. We did not perform a meta-analysis due
      to variability in reporting and follow-up intervals for the primary and secondary
      outcomes of interest. MAIN RESULTS: We included four RCTs involving 216
      participants (range of 2 to 140 participants with uveitic cataract per trial) and
      comparing up to four types of IOLs. The largest study was an international study
      with centers in Brazil, Egypt, Finland, France, Japan, the Netherlands, Slovak
      Republic, Spain, and the USA; two studies were conducted in Germany and one in
      Saudi Arabia. There was substantial heterogeneity with respect to the ages of
      participants and etiologies of uveitis within and across studies. The length of
      follow-up among the studies ranged from 1 to 24 months after cataract surgery.
      The studies were at low risk of selection bias, but two of the four studies did
      not employ masking and only one study included all randomized participants in the
      final analyses. The funding source was disclosed by investigators of the largest
      study (professional society) and not reported by the other three. Due to
      heterogeneity in lens types evaluated and outcomes reported among the trials, we
      did not combine data in a meta-analysis.In the largest study (140 participants),
      the study eye of each participant was randomized to receive one of four types of
      IOLs: hydrophobic acrylic, silicone, HSM PMMA, or unmodified PMMA. Proportions of
      participants with one or more Snellen lines of visual improvement were similar
      among the four treatment groups at one year' follow-up: 45 of 48 (94%) in the
      hydrophobic acrylic IOL group, 39 of 44 (89%) in the silicone IOL group, 18 of 22
      (82%) in the HSM PMMA IOL group, and 22 of 26 (85%) in the unmodified PMMA IOL
      group. When comparing hydrophobic acrylic IOLs with silicone IOLs, the risk ratio
      (RR) was 1.06 (95% confidence interval (CI) 0.93 to 1.20). At one year' follow
      up, fewer eyes randomized to hydrophobic acrylic IOLs developed posterior
      synechiae when compared with eyes receiving silicone IOLs (RR 0.18, 95% CI 0.04
      to 0.79); the effects between these groups were less certain with respect to
      developing posterior capsule opacification (PCO) (RR 0.74, 95% CI 0.41 to 1.37),
      corneal edema (RR 0.49, 95% CI 0.22 to 1.12), cystoid macular edema (RR 0.10, 95%
      CI 0.01 to 1.84), or mild IOL decentration (RR 0.92, 95% CI 0.06 to 14.22).Two
      intra-individual studies also compared HSM PMMA IOLs with unmodified PMMA IOLs at
      three or six months of follow-up. These studies, including a combined total of 16
      participants with uveitis, were insufficiently powered to detect differences in
      outcomes among eyes of people with uveitis randomized to receive HSM PMMA IOLs
      when compared with fellow eyes receiving unmodified PMMA IOLs.In the fourth study
      (60 participants), the study eye of each participant was randomized to receive a
      hydrophobic or hydrophilic acrylic IOL. At three months, there were no
      statistical or clinical differences between hydrophobic and hydrophilic acrylic
      IOL types in the proportions of participants with two or more Snellen lines of
      visual improvement (RR 1.03, 95% CI 0.87 to 1.22). There were similar rates in
      the development of PCO between hydrophobic or hydrophilic acrylic IOLs at six
      months' follow-up (RR 1.00, 95% CI 0.80 to 1.25). The effect of the lenses on
      posterior synechiae was uncertain at six months' follow-up (RR 0.50, 95% CI 0.05
      to 5.22).None of the included studies reported quality of life outcomes. AUTHORS'
      CONCLUSIONS: Based on the trials identified in this review, there is uncertainty
      as to which type of IOL provides the best visual and clinical outcomes in people
      with uveitis undergoing cataract surgery. The studies were small, not all lens
      materials were compared in all studies, and not all lens materials were available
      in all study sites. Evidence of a superior effect of hydrophobic acrylic lenses
      over silicone lenses, specifically for posterior synechiae outcomes comes from a
      single study at a high risk of performance and detection bias. However, due to
      small sample sizes and heterogeneity in outcome reporting, we found insufficient
      information to assess these and other types of IOL materials for cataract surgery
      for eyes with uveitis.

PMID- 24590673
TI  - Prognostic value of total tumor volume in advanced-stage laryngeal and
      hypopharyngeal carcinoma.
AB  - BACKGROUND: To evaluate the prognostic value of total tumor volume (TTV) in
      patients with laryngeal and hypopharyngeal carcinomas. METHODS: This study
      involved 182 patients with previously untreated advanced-stage squamous cell
      carcinoma of the larynx or hypopharynx. TTV were calculated from pretreatment
      contrast-enhanced computed tomography images. Univariate and multivariate
      analyses were used to identify factors associated with overall (OS), disease
      specific (DSS), and disease-free survival (DFS). RESULTS: At a median follow-up
      of 63 months (range, 24-139 months), the 5 year OS, DSS, and DFS rates were
      60.2%, 73.1%, and 69.4%, respectively. Multivariate analyses showed that tumor
      site was an independent predictor of DSS (P = 0.03); Charlson comorbidity index
      for OS (P = 0.001); second primary cancer for OS (P = 0.008) and DFS (P = 0.001);
      and vocal fold paralysis for DSS (P = 0.014) and DFS (P = 0.033). Extension to
      the tongue base was an independent predictor of OS (P = 0.007), DSS (P < 0.001),
      and DFS (P = 0.017), and TTV >=8.38 ml was an independent predictor of all three
      survivals (P < 0.001 each). CONCLUSION: Radiologically determined TTV is
      prognostic of survival in patients with advanced-stage laryngeal and
      hypopharyngeal carcinoma.

PMID- 24590674
TI  - Gastric outlet obstruction in gastric cancer: a comparison of three palliative
      methods.
AB  - BACKGROUND: Gastric outlet obstruction (GOO) commonly occurs in advanced gastric
      cancer. Our aim was to evaluate the results of endoscopic stenting (ES),
      palliative resection (PR), and gastrojejunostomy (GJ) as palliation of GOO.
      METHODS: A total of 97 patients (50 ES, 26 PR, 21 GJ) were included in this
      retrospective study. All the patients had primary gastric cancer and symptoms of
      GOO. RESULTS: Compared to surgery, ES resulted in a faster improvement on oral
      intake and symptom relief (P < 0.001) and a shorter hospitalization (P < 0.001).
      Complication rates, hospital re-admissions, occurrence of biliary obstruction,
      and the number of patients receiving chemotherapy were similar. The median
      symptom-free and overall survival were longest in the PR group (P < 0.001). In
      multivariate survival analysis, independent prognostic factors were age, BMI, pre
      procedure GOOSS, palliative resection as treatment modality, and chemotherapy.
      CONCLUSIONS: In gastric cancer and GOO, the clinical condition of the patient
      before treatment affects survival and should be taken into account in determining
      the treatment. PR seems to provide a survival benefit and should be considered as
      treatment option for patients suitable for surgery. For patients unfit for
      surgery, ES provides rapid and efficient palliation. Chemotherapy also seems to
      improve survival in gastric cancer and GOO.

PMID- 24590675
TI  - Cytobank: providing an analytics platform for community cytometry data analysis
      and collaboration.
AB  - Cytometry is used extensively in clinical and laboratory settings to diagnose and
      track cell subsets in blood and tissue. High-throughput, single-cell approaches
      leveraging cytometry are developed and applied in the computational and systems
      biology communities by researchers, who seek to improve the diagnosis of human
      diseases, map the structures of cell signaling networks, and identify new cell
      types. Data analysis and management present a bottleneck in the flow of knowledge
      from bench to clinic. Multi-parameter flow and mass cytometry enable
      identification of signaling profiles of patient cell samples. Currently, this
      process is manual, requiring hours of work to summarize multi-dimensional data
      and translate these data for input into other analysis programs. In addition, the
      increase in the number and size of collaborative cytometry studies as well as the
      computational complexity of analytical tools require the ability to assemble
      sufficient and appropriately configured computing capacity on demand. There is a
      critical need for platforms that can be used by both clinical and basic
      researchers who routinely rely on cytometry. Recent advances provide a unique
      opportunity to facilitate collaboration and analysis and management of cytometry
      data. Specifically, advances in cloud computing and virtualization are enabling
      efficient use of large computing resources for analysis and backup. An example is
      Cytobank, a platform that allows researchers to annotate, analyze, and share
      results along with the underlying single-cell data. 

PMID- 24590678
TI  - Tetanus toxin preserves skeletal muscle contractile force and size during limb
      immobilization.
AB  - INTRODUCTION: We examined the possibility that tetanus toxin can prevent muscle
      atrophy associated with limb immobility in rats. METHODS: While the knee and
      ankle joints were immobilized unilaterally, the tibialis anterior (TA) muscle on
      the immobilized side was injected with 1 MUl saline or with 1 ng tetanus toxin.
      After 2 weeks, TA wet weights, contractile forces, and myofiber sizes from the
      immobilized sides were compared with those from body weight-matched normal
      animals. RESULTS: Saline group wet weights decreased and produced less absolute
      twitch and tetanic force and normalized tetanic force compared with the toxin or
      normal groups. Cross-sectional areas of saline group type I, IIa, and IId
      myofibers, and the masses of saline group IIa, IId, IIb, and toxin group IIb
      myofibers, were smaller compared with the normal group. CONCLUSIONS: Tetanus
      toxin prevented common signs of muscle atrophy and may become a useful adjunct to
      current rehabilitation strategies.

PMID- 24590679
TI  - Temporal changes in the sensitivity of coastal Antarctic zooplankton communities
      to diesel fuel: a comparison between single- and multi-species toxicity tests.
AB  - Despite increasing human activity and risk of fuel spills in Antarctica, little
      is known about the impact of fuel on Antarctic marine fauna. The authors
      performed both single- and multi-species (whole community) acute toxicity tests
      to assess the sensitivity of an Antarctic coastal zooplankton community to the
      water-accommodated fraction of Special Antarctic Blend diesel. Single-species
      tests using abundant copepods Oncaea curvata, Oithona similis, and Stephos
      longipes allowed comparisons of sensitivity of key taxa and of sensitivity
      estimates obtained from traditional single-species and more novel multi-species
      tests. Special Antarctic Blend diesel caused significant mortality and species
      compositional change in the zooplankton community within 4 d to 7 d. The
      sensitivity of the community also increased across the summer sampling period,
      with decreasing 7-d median lethal concentration (LC50) values for total petroleum
      hydrocarbons (TPH): 1091 ug TPH/L in early January 2011, 353 ug TPH/L in mid
      January 2011, and 186 ug TPH/L in early February 2011. Copepods showed similar
      sensitivities to Special Antarctic Blend diesel in single-species tests (7-d
      LC50s: O. curvata, 158 ug TPH/L; O. similis, 176 ug TPH/L; S. longipes, 188 ug
      TPH/L). The combined use of single- and multi-species toxicity tests is a
      holistic approach to assessing the sensitivity of key species and the
      interactions and interdependence between species, enabling a broader
      understanding of the effects of fuel exposure on the whole zooplankton community.

PMID- 24590676
TI  - Genomic science in understanding cholera outbreaks and evolution of Vibrio
      cholerae as a human pathogen.
AB  - Modern genomic and bioinformatic approaches have been applied to interrogate the
      V. cholerae genome, the role of genomic elements in cholera disease, and the
      origin, relatedness, and dissemination of epidemic strains. A universal attribute
      of choleragenic strains includes a repertoire of pathogenicity islands and
      virulence genes, namely the CTXphi prophage and Toxin Co-regulated Pilus (TCP) in
      addition to other virulent genetic elements including those referred to as
      Seventh Pandemic Islands. During the last decade, the advent of Next Generation
      Sequencing (NGS) has provided highly resolved and often complete genomic
      sequences of epidemic isolates in addition to both clinical and environmental
      strains isolated from geographically unconnected regions. Genomic comparisons of
      these strains, as was completed during and following the Haitian outbreak in
      2010, reveals that most epidemic strains appear closely related, regardless of
      region of origin. Non-O1 clinical or environmental strains may also possess some
      virulence islands, but phylogenic analysis of the core genome suggests they are
      more diverse and distantly related than those isolated during epidemics. Like
      Haiti, genomic studies that examine both the Vibrio core and pan-genome in
      addition to Single Nucleotide Polymorphisms (SNPs) conclude that a number of
      epidemics are caused by strains that closely resemble those in Asia, and often
      appear to originate there and then spread globally. The accumulation of SNPs in
      the epidemic strains over time can then be applied to better understand the
      evolution of the V. cholerae genome as an etiological agent. 

PMID- 24590680
TI  - Safety and efficacy of lactoferrin versus ferrous sulphate in curing iron
      deficiency and iron deficiency anaemia in hereditary thrombophilia pregnant
      women: an interventional study.
AB  - Objective Evaluate the safety and efficacy of bovine lactoferrin (bLf) versus the
      ferrous sulphate standard intervention in curing iron deficiency (ID) and ID
      anaemia (IDA) in pregnant women affected by hereditary thrombophilia (HT). Design
      Interventional study. Setting Secondary-level hospital for complicated
      pregnancies in Rome, Italy. Population 295 HT pregnant women (>=18 years)
      suffering from ID/IDA. Methods Women were enrolled in Arm A or B in accordance
      with their personal choice. In Arm A, 156 women received oral administration of
      100 mg of bLf twice a day; in Arm B, 139 women received 520 mg of ferrous
      sulphate once a day. Therapies lasted until delivery. Main outcome measures Red
      blood cells, haemoglobin, total serum iron, serum ferritin (haematological
      parameters) were assayed before and every 30 days during therapy until delivery.
      Serum IL-6, key factor in inflammatory and iron homeostasis disorders, was
      detected at enrolment and after therapy at delivery. Possible maternal, foetal,
      and neonatal adverse effects were assessed. Results Haematological parameters
      were significantly higher in Arm A than in Arm B pregnant women (P <= 0.0001).
      Serum IL-6 significantly decreased in bLf-treated women and increased in ferrous
      sulphate-treated women. BLf did not exert any adverse effect. Adverse effects in
      16.5 % of ferrous sulphate-treated women were recorded. Arm A women experienced
      no miscarriage compared to five miscarriages in Arm B women. Conclusions
      Differently from ferrous sulphate, bLf is safe and effective in curing ID/IDA
      associated with a consistent decrease of serum IL-6. The absence of miscarriage
      among bLf-treated women provided an unexpected benefit. TRIAL REGISTRATION:
      ClinicalTrials.gov Identifier NCT01221844.

PMID- 24590681
TI  - Confining phosphanes derived from cyclodextrins for efficient regio- and
      enantioselective hydroformylation.
AB  - Two confining phosphane ligands derived from either alpha- or beta-cyclodextrin
      produce singly P(III) -ligated metal complexes with unusual coordination spheres.
      High-pressure NMR studies have revealed that rhodium hydride complexes of the
      same type are also formed under hydroformylation conditions. This unique feature
      strongly favors the formation of the branched aldehyde at the expense of the
      linear one with high enantioselectivity in the rhodium-catalyzed hydroformylation
      of styrene. 

PMID- 24590682
TI  - What is microglia neurotoxicity (Not)?
AB  - Microglia most likely appeared early in evolution as they are not only present in
      vertebrates, but are also found in nervous systems of various nonvertebrate
      organisms. Mammalian microglia are derived from a specific embryonic, self
      renewable myeloid cell population that is throughout lifetime not replaced by
      peripheral myeloid cells. These phylogenic and ontogenic features suggest that
      microglia serve vital functions. Yet, microglia often are described as neurotoxic
      cells, that actively kill (healthy) neurons. Since it is from an evolutionary
      point of view difficult to understand why an important and vulnerable organ like
      the brain should host numerous potential killers, we here review the concept of
      microglia neurotoxicity. On one hand it is discussed that most of our
      understanding about how microglia kill neurons is based on in vitro experiments
      or correlative staining studies that suffer from the difficulty to discriminate
      microglia and peripheral myeloid cells in the diseased brain. On the other hand
      it is described that a more functional approach by mutating, inactivating or
      deleting microglia is seldom associated with a beneficial outcome in an acute
      injury situation, suggesting that microglia are normally important protective
      elements in the brain. This might change in chronic disease or the aged brain,
      where; however, it remains to be established whether microglia simply lose their
      protective capacities or whether microglia become truly neurotoxic cells.

PMID- 24590683
TI  - A vision for drug discovery and development: novel targets and multilateral
      partnerships.

PMID- 24590684
TI  - Association of television viewing time with central obesity status in rural Asian
      Indian women: Santiniketan women study.
AB  - OBJECTIVES: The present community based cross-sectional study aimed to
      investigate anthropometric and body composition measures, and blood pressure
      characteristics by TV viewing times in rural women of Asian Indian Origin.
      METHODS: A total of 343 apparently healthy rural Asian Indian women living in and
      around Santiniketan, West Bengal, India and aged between 25 and 65 years took
      part in the study. Anthropometric measures namely body mass index (BMI),
      percentages of body fat (PBF), basal metabolic rate (BMR), and intra-abdominal
      visceral fat (IVF) were measured using an Omron body fat analyzer. Fat mass (FM),
      fat free mass (FFM), arm muscle area (AMA), arm fat area (AFA), and arm muscle
      circumference (AMC) were calculated using standard techniques. Each individual
      was also asked how many minutes/day they spend watching TV. RESULTS: Comparison
      of central obesity status (CNO = waist circumference < 80 cm and CO = waist
      circumference >= 80 cm) by TV viewing times (categories) revealed a significant
      difference [chi(3)2 14.29] for central obesity status across the groups.
      CONCLUSION: Increased leisure-time activity was associated with central obesity
      status and warrant early intervention to prevent increasing incidences of
      cardiovascular disease in this population.

PMID- 24590685
TI  - Pomalidomide: a review of its use in patients with recurrent multiple myeloma.
AB  - Oral pomalidomide (Imnovid(r) [EU]; Pomalyst(r) [USA]) in combination with
      dexamethasone (in the EU), is approved in several countries for the treatment of
      adult patients with relapsed and refractory multiple myeloma who have received at
      least two prior therapies, including lenalidomide and bortezomib, and have
      demonstrated disease progression on the last therapy (or progression within the
      last 60 days in the USA). The key therapeutic mechanisms of action of
      pomalidomide, a thalidomide analogue, reside in its immunomodulatory,
      antiproliferative and anti-angiogenic effects. In the pivotal, multinational
      phase II MM-002 and phase III MM-003 trials, pomalidomide plus low-dose
      dexamethasone was effective and had a manageable safety and tolerability profile
      in adult patients with relapsed and refractory multiple myeloma who had received
      at least two prior antimyeloma therapies, including at least 2 cycles of both
      lenalidomide and bortezomib. Moreover, compared with high-dose dexamethasone,
      treatment with pomalidomide plus low-dose dexamethasone significantly prolonged
      progression-free survival, overall survival and time to disease progression, and
      improved overall response rates in the intent-to-treat population. In general,
      improvements in these clinical outcomes with pomalidomide plus low-dose
      dexamethasone treatment were also observed in subgroups of patients, including
      those refractory to lenalidomide, bortezomib or both drugs, those who had
      received several prior antimyeloma therapies, patients with renal impairment,
      elderly patients and those with a high-risk cytogenetic profile. Thus,
      combination therapy with pomalidomide plus low-dose dexamethasone is an important
      emerging treatment option for use as salvage therapy in patients with relapsed
      and refractory multiple myeloma.

PMID- 24590686
TI  - 1,2,4-oxadiazole-based bent-core liquid crystals with cybotactic nematic phases.
AB  - Several series of bent-core mesogens derived from 3,5-diphenyl-1,2,4-oxadiazole
      with or without lateral groups and with different length terminal chains at both
      ends, and polycatenar molecules with three to six alkoxy chains are synthesized
      and their mesomorphic behaviour is investigated by polarizing microscopy,
      differential scanning calorimetry, X-ray diffraction (XRD), dielectric, electro
      optical and second-harmonic generation (SHG) experiments. Most compounds exhibit
      broad regions of skewed cybotactic nematic (NcybC ) and tilted smectic (SmC)
      phases with a strong tilt of the aromatic cores (up to 63 degrees ), but non
      tilted SmA and NcybA phases are also observed for a compound that has only one
      terminal chain. The XRD patterns of the nematic phases of most of the compounds
      investigated indicate a 2D periodicity with short correlation length in the
      magnetically aligned samples. This is of importance for the general
      interpretation of the small-angle XRD splitting patterns typically observed for
      aligned samples of bent-core nematic phases. In most nematic phases one current
      peak is observed in the half period of an applied electric field, though no
      coherent signal is found in the SHG experiments. Based on additional electro
      optical and dielectric results, the nematic phases are considered to be
      cybotactic nematic phases with local polar order, and show a dielectric
      reorientation of the polar domains. Only chiral nematic phases (NcybC *), but not
      blue phases, are obtained for compounds with one or two chiral (3S)-3,7
      dimethyloctyloxy tail(s). 

PMID- 24590687
TI  - Percutaneous pulmonary vein stenosis angioplasty complicated by rupture:
      successful stenting with a polytetrafluoroethylene-covered stent.
AB  - A 47-year-old-man with prior pulmonary vein (PV) isolation for atrial
      fibrillation developed progressive shortness of breath and was found to have
      total occlusion of the left lower and significant stenosis in left upper PV. A
      ventilation/perfusion scan showed decreased left lung perfusion. Percutaneous PV
      stenosis angioplasty was complicated by the rupture of left lower PV with
      pericardial tamponade; successful stenting with a polytetrafluoroethylene-covered
      stent was performed. Follow-up studies at nine months showed patency of both
      veins with a normal ventilation perfusion scan. In this article, we will discuss
      acquired PV stenosis following PV isolation, percutaneous PV intervention, and
      the literature supporting the procedure.

PMID- 24590688
TI  - Enhancement of functional connectivity, working memory and inhibitory control on
      multi-modal brain MR imaging with Rifaximin in Cirrhosis: implications for the
      gut-liver-brain axis.
AB  - Minimal hepatic encephalopathy (MHE) impairs daily functioning in cirrhosis, but
      its functional brain impact is not completely understood. To evaluate the effect
      of rifaximin, a gut-specific antibiotic, on the gut-liver-brain axis in MHE.
      HYPOTHESIS: Rifaximin will reduce endotoxemia, enhance cognition, increase
      activation during working memory(N-back) and reduce activation needed for
      inhibitory control tasks. METHODS: Cirrhotics with MHE underwent baseline
      endotoxin and cognitive testing, then underwent fMRI, diffusion tensor imaging
      and MR spectroscopy(MRS). On fMRI, two tasks; N-back (outcome: correct responses)
      and inhibitory control tests(outcomes: lure inhibition) were performed. All
      procedures were repeated after 8 weeks of rifaximin. RESULTS were compared
      before/after rifaximin. RESULTS: 20 MHE patients (59.7 years) were included;
      sixteen completed pre/post-rifaximin scanning with 92% medication compliance. Pre
      rifaximin patients had cognitive impairment. At trial-end, there was a
      significantly higher correct 2-back responses, ICT lure inhibitions and reduced
      endotoxemia(p = 0.002). This was accompanied by significantly higher activation
      from baseline in subcortical structures (thalamus, caudate, insula and
      hippocampus) and left parietal operculum (LPO) during N-back, decrease in fronto
      parietal activation required for inhibiting lures, including LPO during ICT
      compared to baseline values. Connectivity studies in N-back showed significant
      shifts in linkages after therapy in fronto-parietal regions with a reduction in
      fractional anisotropy (FA) but not mean diffusivity (MD), and no change in MRS
      metabolites at the end of the trial. A significant improvement in cognition
      including working memory and inhibitory control, and fractional anisotropy
      without effect on MD or MRS, through modulation of fronto-parietal and
      subcortical activation and connectivity was seen after open-label rifaximin
      therapy in MHE.

PMID- 24590689
TI  - Differential production of reactive oxygen species in distinct brain regions of
      hypoglycemic mice.
AB  - Hypoglycemia is a serious complication of insulin therapy in patients suffering
      from type 1 Diabetes Mellitus. Severe hypoglycemia leading to coma
      (isoelectricity) induces massive neuronal death in vulnerable brain regions such
      as the hippocampus, the striatum and the cerebral cortex. It has been suggested
      that the production of reactive oxygen species (ROS) and oxidative stress is
      involved in hypoglycemic brain damage, and that ROS generation is stimulated by
      glucose reintroduction (GR) after the hypoglycemic coma. However, the
      distribution of ROS in discrete brain regions has not been studied in detail.
      Using the oxidation sensitive marker dihydroethidium (DHE) we have investigated
      the distribution of ROS in different regions of the mouse brain during prolonged
      severe hypoglycemia without isoelectricity, as well as the effect of GR on ROS
      levels. Results show that ROS generation increases in the hippocampus, the
      cerebral cortex and the striatum after prolonged severe hypoglycemia before the
      coma. The hippocampus showed the largest increases in ROS levels. GR further
      stimulated ROS production in the hippocampus and the striatum while in the
      cerebral cortex, only the somatosensory and parietal areas were significantly
      affected by GR. Results suggest that ROS are differentially produced during the
      hypoglycemic insult and that a different response to GR is present among distinct
      brain regions. 

PMID- 24590690
TI  - Thiamine triphosphate: a ubiquitous molecule in search of a physiological role.
AB  - Thiamine triphosphate (ThTP) was discovered over 60 years ago and it was long
      thought to be a specifically neuroactive compound. Its presence in most cell
      types, from bacteria to mammals, would suggest a more general role but this
      remains undefined. In contrast to thiamine diphosphate (ThDP), ThTP is not a
      coenzyme. In E. coli cells, ThTP is transiently produced in response to amino
      acid starvation, while in mammalian cells, it is constitutively produced at a low
      rate. Though it was long thought that ThTP was synthesized by a ThDP:ATP
      phosphotransferase, more recent studies indicate that it can be synthesized by
      two different enzymes: (1) adenylate kinase 1 in the cytosol and (2) FoF1-ATP
      synthase in brain mitochondria. Both mechanisms are conserved from bacteria to
      mammals. Thus ThTP synthesis does not seem to require a specific enzyme. In
      contrast, its hydrolysis is catalyzed, at least in mammalian tissues, by a very
      specific cytosolic thiamine triphosphatase (ThTPase), controlling the steady
      state cellular concentration of ThTP. In some tissues where adenylate kinase
      activity is high and ThTPase is absent, ThTP accumulates, reaching >= 70% of
      total thiamine, with no obvious physiological consequences. In some animal
      tissues, ThTP was able to phosphorylate proteins, and activate a high-conductance
      anion channel in vitro. These observations raise the possibility that ThTP is
      part of a still uncharacterized cellular signaling pathway. On the other hand,
      its synthesis by a chemiosmotic mechanism in mitochondria and respiring bacteria
      might suggest a role in cellular energetics.

PMID- 24590693
TI  - Interventions for improving patients' trust in doctors and groups of doctors.
AB  - BACKGROUND: Trust is a fundamental component of the patient-doctor relationship
      and is associated with increased satisfaction, adherence to treatment, and
      continuity of care. Our 2006 review found little evidence that interventions
      improve patients' trust in their doctor; therefore an updated search was required
      to find out if there is further evidence of the effects of interventions that may
      improve trust in doctors or groups of doctors. OBJECTIVES: To update our earlier
      review assessing the effects of interventions intended to improve patients' trust
      in doctors or a group of doctors. SEARCH METHODS: In 2003 we searched the
      Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library),
      MEDLINE, EMBASE, Health Star, PsycINFO, CINAHL, LILACS, African Trials Register,
      African Health Anthology, Dissertation Abstracts International and the
      bibliographies of studies selected for inclusion. We also contacted researchers
      active in the field. We updated and re-ran the searches on available original
      databases (Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane
      Library issue 2, 2013), MEDLINE (OvidSP), EMBASE (OvidSP), PsycINFO (OvidSP),
      CINAHL (Ebsco)) as well as Proquest Dissertations and Current Contents for the
      period 2003 to 18 March 2013. SELECTION CRITERIA: Randomised controlled trials
      (RCTs), quasi-randomised controlled trials, controlled before and after studies,
      and interrupted time series of interventions (informative, educational,
      behavioural, organisational) directed at doctors or patients (or carers) where
      trust was assessed as a primary or secondary outcome. DATA COLLECTION AND
      ANALYSIS: Two review authors independently extracted data and assessed the risk
      of bias of included studies. Where mentioned, we extracted data on adverse
      effects. We synthesised data narratively. MAIN RESULTS: We included 10 randomised
      controlled trials (including 7 new trials) involving 11,063 patients. These
      studies were all undertaken in North America, and all but two involved primary
      care.  As expected, there was considerable heterogeneity between the studies. 
      Interventions were of three main types; three employed additional physician
      training, four were education for patients and three provided additional
      information about doctors in terms of financial incentives or consulting style.
      Additionally, several different measures of trust were employed.The studies gave
      conflicting results. Trials showing a small but statistically-significant
      increase in trust included: a trial of physician disclosure of financial
      incentives; a trial of providing choice of physician based on concordance between
      patient and physician beliefs about care; a trial of group visits for new
      inductees into a Health Maintenance Organisation; a trial of training oncologists
      in communication skills; and a trial of group visits for diabetic patients.
      However, trust was not affected in a subsequent larger trial of group visits for
      uninsured people with diabetes, nor with a decision aid for helping choose
      statins, another trial of disclosure of financial incentives or specifically
      training doctors to increase trust or cultural competence. There was no evidence
      of harm from any of the studies. AUTHORS' CONCLUSIONS: Overall, there remains
      insufficient evidence to conclude that any intervention may increase or decrease
      trust in doctors. This may be due in part to the sensitivity of trust
      instruments, and a ceiling effect, as trust in doctors is generally high. It may
      be that current measures of trust are insufficiently sensitive. Further trials
      are required to explore the impact of doctors' specific training or the use of a
      patient-centred or decision-sharing approach on patients' trust, especially in
      the areas of healthcare provider choice, and induction into healthcare
      organisation. International trials would be of particular benefit. The review was
      constrained by the lack of consistency between trust measurements, timeframes and
      populations.

PMID- 24590692
TI  - Diagnostic challenges of respiratory adverse events during everolimus treatment.
AB  - Everolimus has important clinical activity in various malignancies, but its use
      can be complicated by respiratory adverse events. Important everolimus-induced
      respiratory adverse events are interstitial lung disease (ILD) and infections,
      either typical or opportunistic. Furthermore, non-everolimus-related respiratory
      events can occur. Due to the non-specific presentation of most of these
      respiratory disorders, it is often not possible to differentiate between these
      causes on clinical and radiological grounds only. Considering the potential fatal
      nature of opportunistic infections, these are especially important to recognize.
      To be able to distinguish between ILD and (opportunistic) infections as the
      underlying cause, an aggressive diagnostic workup, including bronchoalveolar
      lavage, should be performed in patients treated with everolimus who develop
      respiratory disease. We report three cases of severe opportunistic pulmonary
      infections during everolimus treatment, concerning two Pneumocystis jirovecii
      pneumonia infections. These cases illustrate the diagnostic challenges of
      respiratory adverse events and the importance of a thorough diagnostic workup for
      correct diagnosis and treatment. 

PMID- 24590691
TI  - Transforming growth factor-beta and its implication in the malignancy of gliomas.
AB  - Malignant gliomas are the most common type of primary malignant brain tumors.
      They are characterized by enhanced growing capabilities, neoangiogenic
      proliferation, and extensive infiltration of the brain parenchyma, which make
      their complete surgical resection impossible. Together with transient and
      refractory responses to standard therapy, these aggressive neoplasms are
      incurable and present a median survival of 12 to 14 months. Transforming growth
      factor-beta (TGF-beta) is a pleiotropic cytokine of which two of the three
      isoforms expressed in humans have been shown to be overexpressed proportionally
      to the histologic grade of glioma malignancy. The increase of chromosomal
      aberrations and genetic mutations observed in glioma cells turns TGF-beta into an
      oncogene. For that reason, it plays critical roles in glioma progression through
      induction of several genes implicated in many carcinogenic processes such as
      proliferation, angiogenesis, and invasion. Consequently, investigators have begun
      developing innovative therapeutics targeting this growth factor or its signaling
      pathway in an attempt to hinder TGF-beta's appalling effects in order to refine
      the treatment of malignant gliomas and improve their prognosis. In this paper, we
      extensively review the TGF-beta-induced oncogenic pathways and discuss the
      diverse new molecules targeting this growth factor.

PMID- 24590694
TI  - Concurrent phosphorus doping and reduction of graphene oxide.
AB  - Doped graphene materials are of huge importance because doping with electron
      donating or electron-withdrawing groups can significantly change the electronic
      structure and impact the electronic and electrochemical properties of these
      materials. It is highly important to be able to produce these materials in large
      quantities for practical applications. The only method capable of large-scale
      production is the oxidative treatment of graphite to graphene oxide, followed by
      its consequent reduction. We describe a scalable method for a one-step doping of
      graphene with phosphorus, with a simultaneous reduction of graphene oxide. Such a
      method is able to introduce significant amount of dopant (3.65 at. %). Phosphorus
      doped graphene is characterized in detail and shows important electronic and
      electrochemical properties. The electrical conductivity of phosphorus-doped
      graphene is much higher than that of undoped graphene, owing to a large
      concentration of free carriers. Such a graphene material is expected to find
      useful applications in electronic, energy storage, and sensing devices. 

PMID- 24590696
TI  - Abstracts from the American Society for Apheresis 35th Annual Meeting, April 2-5,
      2014, San Francisco, California.

PMID- 24590695
TI  - Sequence and 3D structure based analysis of TNT degrading proteins in Arabidopsis
      thaliana.
AB  - TNT, accidentally released at several manufacturing sites, contaminates ground
      water and soil. It has a toxic effect to algae and invertebrate, and chronic
      exposure to TNT also causes harmful effects to human. On the other hand, many
      plants including Arabidopsis thaliana have the ability to metabolize TNT either
      completely or at least to a reduced less toxic form. In A. thaliana, the enzyme
      UDP glucosyltransferase (UDPGT) can further conjugate the reduced forms 2-HADNT
      and 4-HADNT (2-hydroxylamino-4, 6- dinitrotoluene and 4-hydroxylamino-2, 6-
      dinitrotoluene) of TNT. Based on the experimental analysis, existing literature
      and phylogenetic analysis, it is evident that among 107 UDPGT proteins only six
      are involved in the TNT degrading process. A total of 13 UDPGT proteins including
      five of these TNT degrading proteins fall within the same group of phylogeny.
      Thus, these 13 UDPGT proteins have been classified into two groups, TNT-degrading
      and TNT-non-degrading proteins. To understand the differences in TNT-degrading
      capacities; using homology modeling we first predicted two structures, taking one
      representative sequence from both the groups. Next, we performed molecular
      docking of the modeled structure and TNT reduced form 2-hydroxylamino-4, 6-
      dinitrotoluene (2-HADNT). We observed that while the Trp residue located within
      the active site region of the TNT- degrading protein showed pi-Cation
      interaction; such type of interaction was absent in TNT-non-degrading protein, as
      the respective Trp residue lay outside of the pocket in this case. We observed
      the conservation of this pi-Cation interaction during MD simulation of TNT
      degrading protein. Thus, the position and the orientation of the active site
      residue Trp could explain the presence and absence of TNT-degrading capacity of
      the UDPGT proteins. 

PMID- 24590697
TI  - [Embrace, a model for integrated elderly care].
AB  - Ongoing growth in health care expenditures and changing patterns in the demand
      for health care challenge societies worldwide. The Chronic Care Model (CCM),
      combined with classification for care needs based on Kaiser Permanente (KP)
      Triangle, may offer a suitable framework for change. The aim of the present study
      is to investigate the effectiveness of Embrace, a population-based model for
      integrated elderly care, regarding patient outcomes, service use, costs, and
      quality of care. METHODS: The CCM and the KP Triangle were translated to the
      Dutch setting and adapted to the full elderly population living in the community.
      A randomized controlled trial with balanced allocation was designed to test the
      effectiveness of Embrace. Eligible elderly persons are 75 years and older and
      enrolled with one of the participating general practitioner practices. Based on
      scores on the INTERMED-Elderly Self-Assessment and Groningen Frailty Indicator,
      participants will be stratified into one of three strata: (A) robust; (B) frail;
      and (C) complex care needs. Next, participants will be randomized per stratum to
      Embrace or care as usual. Embrace encompasses an Elderly Care Team per general
      practitioner practice, an Electronic Elderly Record System, decision support
      instruments, and a self-management support and prevention program - combined with
      care and support intensity levels increasing from stratum A to stratum C. Primary
      outcome variables are patient outcomes, service use, costs, and quality of care.
      Data will be collected at baseline, twelve months after starting date, and during
      the intervention period. DISCUSSION: This study could provide evidence for the
      effectiveness of Embrace.

PMID- 24590698
TI  - Optimal and nonoptimal choice in a laboratory-based sunk cost task with humans: a
      cross-species replication.
AB  - The current four experiments examined the sunk cost effect-nonoptimal persistence
      following investment-in a laboratory-based decision-making task with adult
      humans. Subjects made repeated decisions about whether to persist in a course of
      action-a fixed-ratio schedule whose response requirements varied unpredictably
      from one trial to the next-or to abandon it and escape in favor of a new trial
      with a potentially smaller fixed ratio schedule. Satisfying the ratio requirement
      produced a brief video clip from a preferred television program. In Experiment 1,
      sunk-cost errors were less likely in subjects who had previously experienced
      markedly differential reinforcement for escape. In Experiment 2, stimulus changes
      correlated with changes in mean response requirement, and these changes reduced
      sunk-cost errors in a small number of subjects. In Experiment 3, sunk-cost errors
      occurred more frequently as the ratio of the mean response requirements for
      persistence and escape approached 1.0. The importance of this variable was
      further supported by the results of Experiment 4, in which features other than
      this ratio did not markedly alter performance. These four experiments identified
      some key determinants of whether humans commit the sunk-cost error and confirmed
      the utility of video clips as reinforcers in experimental research with humans. 

PMID- 24590699
TI  - A multicenter study on the Lebanese experience with hereditary spherocytosis.

PMID- 24590700
TI  - Click-assembled, oxygen-sensing nanoconjugates for depth-resolved, near-infrared
      imaging in a 3D cancer model.
AB  - Hypoxia is an important contributing factor to the development of drug-resistant
      cancer, yet few nonperturbative tools exist for studying oxygenation in tissues.
      While progress has been made in the development of chemical probes for optical
      oxygen mapping, penetration of such molecules into poorly perfused or avascular
      tumor regions remains problematic. A click-assembled oxygen-sensing (CAOS)
      nanoconjugate is reported and its properties demonstrated in an in vitro 3D
      spheroid cancer model. The synthesis relies on the sequential click-based
      ligation of poly(amidoamine)-like subunits for rapid assembly. Near-infrared
      confocal phosphorescence microscopy was used to demonstrate the ability of the
      CAOS nanoconjugates to penetrate hundreds of micrometers into spheroids within
      hours and to show their sensitivity to oxygen changes throughout the nodule. This
      proof-of-concept study demonstrates a modular approach that is readily extensible
      to a wide variety of oxygen and cellular sensors for depth-resolved imaging in
      tissue and tissue models. 

PMID- 24590701
TI  - Breaking the addiction to technology adoption.
AB  - A major driver of cost growth in health care is the rapid increase in the
      utilisation of existing technology and not simply the adoption of new technology.
      Health economists and their health technology assessment colleagues have become
      obsessed by technology adoption questions and have largely ignored 'technology
      management' questions. Technology management would include the life-cycle
      assessment of technologies in use, to assess their real-world performance; and
      monitoring of technology indication creep. A rebalancing of focus might serve to
      encourage a more self-critical and learning culture amongst those involved in
      technology evaluation analysis. Further, health economists and health technology
      assessment analysts could make a more significant contribution to system
      efficiency through rebalancing their efforts away from technology adoption
      questions towards technology management issues.

PMID- 24590702
TI  - Note: The upside of downsizing: asymmetric trifunctional organocatalysts as small
      enzyme mimics for cooperative enhancement of both rate and enantioselectivity
      with regulation.

PMID- 24590704
TI  - The effects of charge compensation on photoluminescence properties of a new green
      emitting ZnB2O4:Tb3+ phosphor.
AB  - Charge compensation is an effective way to eliminate charge defects and improve
      the luminescent intensity of phosphors. In this paper, a new green-emitting
      phosphor ZnB(2)O(4):Tb(3+) was prepared by solid-state reaction at 750  degrees
      C. The effects of Tb(3+) doping content and charge compensators (Li(+), Na(+) or
      K(+)) on photoluminescence properties of ZnB(2)O(4):Tb(3+) were investigated. X
      ray powder diffraction analysis confirms the sample has cubic structure of
      ZnB(2)O(4). The excitation and emission spectra indicate that this phosphor can
      be excited by near ultraviolet light at 378 nm, and exhibits bright green
      emission with the highest peak at 544 nm corresponding to the (5)D4 -> (7)F5
      transition of Tb(3+). The critical quenching concentration of Tb(3+) in
      ZnB(2)O(4) host is 8 mol%. The results of charge compensation show that the
      emission intensity can be improved by Na(+) and K(+). Specifically, K(+) is the
      optimal one for ZnB(2)O(4):Tb(3+).

PMID- 24590706
TI  - Structural genomics of human proteins.
AB  - Structural genomics efforts focused on the human proteome have had three aims: to
      understand the structural and functional variations within protein families; to
      understand the structural basis of disease and genetic variation; and to
      determine the structures of human integral membrane proteins. The overarching
      theme is to advance the understanding of human health and to provide a structural
      platform to aid in the development of therapeutics. A decade or more of work in
      this field has identified optimal experimental strategies that can be used to
      expedite expression and crystallization of human proteins-and we provide some
      guidance to this end.

PMID- 24590705
TI  - Data management in the modern structural biology and biomedical research
      environment.
AB  - Modern high-throughput structural biology laboratories produce vast amounts of
      raw experimental data. The traditional method of data reduction is very simple
      results are summarized in peer-reviewed publications, which are hopefully
      published in high-impact journals. By their nature, publications include only the
      most important results derived from experiments that may have been performed over
      the course of many years. The main content of the published paper is a concise
      compilation of these data, an interpretation of the experimental results, and a
      comparison of these results with those obtained by other scientists.Due to an
      avalanche of structural biology manuscripts submitted to scientific journals, in
      many recent cases descriptions of experimental methodology (and sometimes even
      experimental results) are pushed to supplementary materials that are only
      published online and sometimes may not be reviewed as thoroughly as the main body
      of a manuscript. Trouble may arise when experimental results are contradicting
      the results obtained by other scientists, which requires (in the best case) the
      reexamination of the original raw data or independent repetition of the
      experiment according to the published description of the experiment. There are
      reports that a significant fraction of experiments obtained in academic
      laboratories cannot be repeated in an industrial environment (Begley CG & Ellis
      LM, Nature 483(7391):531-3, 2012). This is not an indication of scientific fraud
      but rather reflects the inadequate description of experiments performed on
      different equipment and on biological samples that were produced with disparate
      methods. For that reason the goal of a modern data management system is not only
      the simple replacement of the laboratory notebook by an electronic one but also
      the creation of a sophisticated, internally consistent, scalable data management
      system that will combine data obtained by a variety of experiments performed by
      various individuals on diverse equipment. All data should be stored in a core
      database that can be used by custom applications to prepare internal reports,
      statistics, and perform other functions that are specific to the research that is
      pursued in a particular laboratory.This chapter presents a general overview of
      the methods of data management and analysis used by structural genomics (SG)
      programs. In addition to a review of the existing literature on the subject, also
      presented is experience in the development of two SG data management systems,
      UniTrack and LabDB. The description is targeted to a general audience, as some
      technical details have been (or will be) published elsewhere. The focus is on
      "data management," meaning the process of gathering, organizing, and storing
      data, but also briefly discussed is "data mining," the process of analysis
      ideally leading to an understanding of the data. In other words, data mining is
      the conversion of data into information. Clearly, effective data management is a
      precondition for any useful data mining. If done properly, gathering details on
      millions of experiments on thousands of proteins and making them publicly
      available for analysis-even after the projects themselves have ended-may turn out
      to be one of the most important benefits of SG programs.

PMID- 24590707
TI  - Target selection for structural genomics of infectious diseases.
AB  - This chapter describes the protocols used to identify, filter, and annotate
      potential protein targets from an organism associated with infectious diseases.
      Protocols often combine computational approaches for mining information in public
      databases or for checking whether the protein has already been targeted for
      structure determination, with manual strategies that examine the literature for
      information on the biological role of the protein or the experimental strategies
      that explore the effects of knocking out the protein. Publicly available
      computational tools have been cited as much as possible. Where these do not
      exist, the concepts underlying in-house tools developed for the Center for
      Structural Genomics of Infectious Diseases have been described. 

PMID- 24590708
TI  - Selecting targets from eukaryotic parasites for structural genomics and drug
      discovery.
AB  - The selection of targets is the first step for any structural genomics project.
      The application of structural genomics approaches to drug discovery also starts
      with the selection of targets. Here, three protocols are described that were
      developed to select targets from eukaryotic pathogens. These protocols could also
      be applied to other drug discovery projects. 

PMID- 24590709
TI  - High-throughput cloning for biophysical applications.
AB  - Efficient high-throughput gene cloning represents a critical first step for
      conducting functional and structural proteomics in the post-genomic era. The
      ligation-independent cloning (LIC) method has been almost universally adopted by
      large structural biology centers as a component of high-throughput structure
      determination pipelines. The LIC platform is easy to use, of low cost, and rapid,
      and importantly, it is easily adapted to 96- or 384-well format, thereby
      facilitating automation. Procedures are described for 96-well format cloning
      using the LIC technology. 

PMID- 24590710
TI  - Expression and solubility testing in a high-throughput environment.
AB  - The expression and screening of the solubility of recombinant proteins is an
      important step in the high-throughput (HT) production of target proteins. For
      many applications, E. coli remains the most widely used expression system due to
      the relative ease of adapting it to HT pipelines. Herein is described a platform
      using a 96-well format for efficient expression and solubility screening of
      target proteins. 

PMID- 24590711
TI  - Protein production for structural genomics using E. coli expression.
AB  - The goal of structural biology is to reveal details of the molecular structure of
      proteins in order to understand their function and mechanism. X-ray
      crystallography and NMR are the two best methods for atomic level structure
      determination. However, these methods require milligram quantities of proteins.
      In this chapter a reproducible methodology for large-scale protein production
      applicable to a diverse set of proteins is described. The approach is based on
      protein expression in E. coli as a fusion with a cleavable affinity tag that was
      tested on over 20,000 proteins. Specifically, a protocol for fermentation of
      large quantities of native proteins in disposable culture vessels is presented. A
      modified protocol that allows for the production of selenium-labeled proteins in
      defined media is also offered. Finally, a method for the purification of His6
      tagged proteins on immobilized metal affinity chromatography columns that
      generates high-purity material is described in detail. 

PMID- 24590712
TI  - Eukaryotic expression systems for structural studies.
AB  - This protocol describes protein production in mammalian cells by transient
      transfection. It assumes the expression construct contains either a 6-HIS or Fc
      fusion tag to allow recovery of the protein by affinity chromatography. The
      method is one of the simplest available for protein expression in eukaryotic
      cells, requires little specialized equipment, and has a reasonably high rate of
      success. 

PMID- 24590713
TI  - Automated cell-free protein production methods for structural studies.
AB  - In contrast to cell-based protein expression, cell-free production is highly
      consistent, scalable, and amenable to automation. Robots can handle many samples
      and perform repetitive procedures that are otherwise prone to human error. Here
      is described commercially available robotics for a wheat germ cell-free system
      with emphasis on practical applications for structural and functional studies. In
      addition, described is a cell-free method for preparing protein complexes. 

PMID- 24590714
TI  - Parallel protein purification.
AB  - Structural genomics has increased demands on protein production laboratories to
      supply large numbers of different proteins in high quantities and qualities in
      shorter times. Extensive experience with many different technologies and
      strategies developed and implemented by structural genomics groups have helped
      identify an optimal approach to purification of a large number of widely
      different proteins. This standardized protocol can be applied to many samples and
      can be used in parallel protein purification. 

PMID- 24590715
TI  - Oxidative refolding from inclusion bodies.
AB  - This protocol describes the growth and purification of bacterial inclusion body
      proteins with an option to selenomethionine label the targeted protein through
      feedback inhibition of methionine biosynthesis in common (non-auxotrophic)
      strains of E. coli. The method includes solubilization of inclusion body proteins
      by chemical denaturation and disulfide reduction, renaturation of the solubilized
      material through rapid dilution by pulsed injection into refolding buffer
      containing arginine and a mixture of oxidized and reduced glutathione, recovery
      of the recombinant protein using a stirred cell concentrator, and removal of the
      aggregated or misfolded fraction by passage over size-exclusion chromatography.
      The quality of the resulting protein can be assessed by SDS-PAGE. 

PMID- 24590716
TI  - High-throughput crystallization screening.
AB  - Protein structure determination by X-ray crystallography is dependent on
      obtaining a single protein crystal suitable for diffraction data collection. Due
      to this requirement, protein crystallization represents a key step in protein
      structure determination. The conditions for protein crystallization have to be
      determined empirically for each protein, making this step also a bottleneck in
      the structure determination process. Typical protein crystallization practice
      involves parallel setup and monitoring of a considerable number of individual
      protein crystallization experiments (also called crystallization trials). In
      these trials the aliquots of purified protein are mixed with a range of solutions
      composed of a precipitating agent, buffer, and sometimes an additive that have
      been previously successful in prompting protein crystallization. The individual
      chemical conditions in which a particular protein shows signs of crystallization
      are used as a starting point for further crystallization experiments. The goal is
      optimizing the formation of individual protein crystals of sufficient size and
      quality to make them suitable for diffraction data collection. Thus the
      composition of the primary crystallization screen is critical for successful
      crystallization.Systematic analysis of crystallization experiments carried out on
      several hundred proteins as part of large-scale structural genomics efforts
      allowed the optimization of the protein crystallization protocol and
      identification of a minimal set of 96 crystallization solutions (the "TRAP"
      screen) that, in our experience, led to crystallization of the maximum number of
      proteins. 

PMID- 24590717
TI  - Screening proteins for NMR suitability.
AB  - NMR spectroscopy is a valuable tool in structural genomics. Identification of
      protein samples that are amenable to structure determination by NMR spectroscopy
      requires efficient screening. The preparation of multiple samples in parallel and
      screening by NMR is described. The method described is applicable to large
      structural genomics projects but can easily be scaled down for application to
      small structural biology projects. All the equipment used is commonly found in
      any NMR structural biology laboratory. 

PMID- 24590718
TI  - Salvage or recovery of failed targets by in situ proteolysis.
AB  - In situ proteolysis is the method of proactively adding tiny amounts of
      nonspecific proteases to aid in the crystallization of proteins and protein
      macromolecular complexes. The simplicity of the procedure and high recovery rate
      make it a method of first choice for recalcitrant targets. An improved and
      updated in situ proteolysis protocol used in high-throughput structural biology
      platforms is described. 

PMID- 24590720
TI  - Salvage or recovery of failed targets by mutagenesis to reduce surface entropy.
AB  - The success of macromolecular crystallization depends on the protein's ability to
      form specific, cohesive intermolecular interactions that serve as crystal
      contacts. In the cases where the protein lacks surface patches conducive to such
      interactions, crystallization may not occur. However, it is possible to enhance
      the likelihood of crystallization by engineering such patches through site
      directed mutagenesis, targeting specifically residues with high side chain
      entropy and replacing them with small amino acids (i.e., surface entropy
      reduction, SER). This method has proven successful in hundreds of
      crystallographic analyses of proteins otherwise recalcitrant to crystallization.
      Three representative cases of the application of the SER strategy, assisted by
      the automated prediction of the mutation sites using the SER prediction (SERp)
      server are described. 

PMID- 24590719
TI  - Salvage of failed protein targets by reductive alkylation.
AB  - The growth of diffraction-quality single crystals is of primary importance in
      protein X-ray crystallography. Chemical modification of proteins can alter their
      surface properties and crystallization behavior. The Midwest Center for
      Structural Genomics (MCSG) has previously reported how reductive methylation of
      lysine residues in proteins can improve crystallization of unique proteins that
      initially failed to produce diffraction-quality crystals. Recently, this approach
      has been expanded to include ethylation and isopropylation in the MCSG protein
      crystallization pipeline. Applying standard methods, 180 unique proteins were
      alkylated and screened using standard crystallization procedures. Crystal
      structures of 12 new proteins were determined, including the first ethylated and
      the first isopropylated protein structures. In a few cases, the structures of
      native and methylated or ethylated states were obtained and the impact of
      reductive alkylation of lysine residues was assessed. Reductive methylation tends
      to be more efficient and produces the most alkylated protein structures.
      Structures of methylated proteins typically have higher resolution limits. A
      number of well-ordered alkylated lysine residues have been identified, which make
      both intermolecular and intramolecular contacts. The previous report is updated
      and complemented with the following new data; a description of a detailed
      alkylation protocol with results, structural features, and roles of alkylated
      lysine residues in protein crystals. These contribute to improved crystallization
      properties of some proteins.

PMID- 24590721
TI  - Data collection for crystallographic structure determination.
AB  - Diffraction data measurement is the final experimental step of crystal structure
      analysis; all subsequent stages are computational. Good-quality data, optimized
      for a particular application, make the structure solution and refinement easier
      and enhance the accuracy of the final models. This chapter describes the
      principles of the rotation method of data collection and discusses various
      scenarios that are useful for different types of applications, such as anomalous
      phasing, molecular replacement, ligand identification, etc. Some typical problems
      encountered in practice are also discussed. 

PMID- 24590722
TI  - Structure determination, refinement, and validation.
AB  - It can be a tremendous advantage to have the X-ray crystal structure of a protein
      that is targeted for drug discovery. Due to recent advances in methods, software
      and hardware, crystallographic structure determination no longer requires a
      specialist in the method, but rather it has become a technique that can be
      readily applied to many research problems. The high-throughput approaches
      developed and used by structural genomics projects can be adapted and used to aid
      drug discovery efforts. It should be emphasized, however, that one cannot blindly
      accept the results of automated approaches and that it is essential to carefully
      validate the model, which is the interpretation of the observed electron density.
      It is important to be sure that it correctly describes the structure.The
      investigator that wishes to make use of the extensive database of protein
      structures in the Protein Data Bank (PDB) also needs to be know how to evaluate
      structural models, understand how they are related to the experimental data and
      be able to utilize computer graphics programs to look at the electron density
      distribution together with the model. 

PMID- 24590723
TI  - Virtual high-throughput ligand screening.
AB  - In Structural Genomics projects, virtual high-throughput ligand screening can be
      utilized to provide important functional details for newly determined protein
      structures. Using a variety of publicly available software tools, it is possible
      to computationally model, predict, and evaluate how different ligands interact
      with a given protein. At the Center for Structural Genomics of Infectious
      Diseases (CSGID) a series of protein analysis, docking and molecular dynamics
      software is scripted into a single hierarchical pipeline allowing for an
      exhaustive investigation of protein-ligand interactions. The ability to conduct
      accurate computational predictions of protein-ligand binding is a vital component
      in improving both the efficiency and economics of drug discovery. Computational
      simulations can minimize experimental efforts, the slowest and most cost
      prohibitive aspect of identifying new therapeutics. 

PMID- 24590724
TI  - Ligand screening using fluorescence thermal shift analysis (FTS).
AB  - The fluorescence thermal shift (FTS) method is a biophysical technique that can
      improve productivity in a structural genomics pipeline and provide a fast and
      easy platform for identifying ligands in protein function or drug discovery
      screening. The technique has gained widespread popularity in recent years due to
      its broad-scale applicability, throughput, and functional relevance. FTS is based
      on the principle that a protein unfolds at a critical temperature that depends
      upon its intrinsic stability. A probe that will fluoresce when bound to
      hydrophobic surfaces is used to monitor protein unfolding as temperature is
      increased. In this manner, conditions or small molecules that affect the thermal
      stability of a protein can be identified. Herein, principles, protocols, data
      analysis, and special considerations of FTS screening as performed for the Center
      for Structural Genomics of Infectious Diseases (CSGID) pipeline are described in
      detail. The CSGID FTS screen is designed as a high-throughput 384-well assay to
      be performed on a robotic platform; however, all protocols can be adapted to a 96
      well format that can be assembled manually. Data analysis can be performed using
      a simple curve fitting of the fluorescent signal using a Boltzmann or double
      Boltzmann equation. A case study of 100 proteins screened against Emerald
      Biosystem's ADDitTM library is included as discussion. 

PMID- 24590725
TI  - Ligand screening using enzymatic assays.
AB  - An important aspect of enzymatic assays is that the effect of a ligand on enzyme
      activity is readily apparent and quantifiable. Enzyme-based assays are,
      therefore, highly amenable to high-throughput ligand screening, which profiles
      the effect of a panel of small molecules on a designated target. In order for
      enzyme assays to provide useful screening data, the kinetics, assay components,
      readout signal, and overall stability of the assay are optimized and adapted to
      the equipment prior to the screen. For the screen itself, careful consideration
      is given to the number of replicates, the plate layout, the compound
      concentration, and the details of assay assembly. Lastly, in the post-screen
      stages, the ligand screening data is processed and analyzed using various
      strategies, and the resulting preliminary hits are subjected to a series of
      secondary and tertiary assays to eliminate false positives and poor quality hits.
      The various stages of screening are described, using a viral protease, NS3/4A
      from Hepatitis C virus, as an example of an enzyme target. 

PMID- 24590726
TI  - Ligand screening using NMR.
AB  - NMR has proven to be an invaluable technique for identifying and characterizing
      ligand interactions with biomolecules. NMR-based detection of ligand binding to
      protein targets is described. Specifically, the use of the WaterLOGSY NMR
      experiment to screen mixtures of compounds from a fragment library for binding to
      influenza H5 hemagglutinin is detailed.

PMID- 24590727
TI  - Screening Ligands by X-ray crystallography.
AB  - X-ray crystallography is an invaluable technique in structure-based drug
      discovery, including fragment-based drug discovery, because it is the only
      technique that can provide a complete three dimensional readout of the
      interaction between the small molecule and its macromolecular target. X-ray
      diffraction (XRD) techniques can be employed as the sole method for conducting a
      screen of a fragment library, or it can be employed as the final technique in a
      screening campaign to confirm putative "hit" compounds identified by a variety of
      biochemical and/or biophysical screening techniques. Both approaches require an
      efficient technique to prepare dozens to hundreds of crystals for data
      collection, and a reproducible way to deliver ligands to the crystal. Here, a
      general method for screening cocktails of fragments is described. In cases where
      X-ray crystallography is employed as a method to verify putative hits, the
      cocktails of fragments described below would simply be replaced with single
      fragment solutions. 

PMID- 24590728
TI  - Case study--structural genomics and human protein kinases.
AB  - A brief summary is made of some of the methods in structural genomics and drug
      discovery as they apply to protein kinases. 

PMID- 24590729
TI  - Robust nonsticky superhydrophobicity by the tapering of aligned ZnO nanorods.
AB  - The robust nonsticky superhydrophobicity of aligned nanoneedle films is reported.
      A facile, efficient, cheap, and available method based on the diffusion-limited
      crystal growth principle is proposed for controlling the tapering of ZnO
      nanorods, the profiles of which can be tuned effectively by synergetic control
      over reaction time and temperature in an extremely strong alkaline reaction
      system. The synthesized nanoneedle, nanopencil, and nanorod arrays are chosen for
      studying the effects of nanoscale topography on anti-droplet-sticking ability.
      After silanization, all of them show excellent quasi-static anti-droplet
      stickiness, and water adhesion along the normal and lateral directions can be
      greatly reduced by the tapering of nanorods and eliminated by sharp nanoneedles.
      However, their antisticking stability is distinct under the droplet impact: the
      nanoneedle sample is still nonsticky but the nanorod sample loses its
      antisticking ability. Only ensuring the liquid/air interface is in the suspended
      nonwetting state is insufficient to obtain robust nonsticky surfaces, which also
      require extremely low solid-liquid van der Waals attraction. 

PMID- 24590730
TI  - Empirical versus natural weighting in random effects meta-analysis by J. J.
      Shuster, Statistics in Medicine 2010; 29(12):1259-65.

PMID- 24590731
TI  - Empirical versus natural weighting in random effects meta-analysis.

PMID- 24590732
TI  - Non-uniform surface electromyographic responses to change in joint angle within
      rectus femoris muscle.
AB  - INTRODUCTION: Our recent studies have demonstrated region-specific neural
      activation within the rectus femoris (RF) muscle. However, these studies involved
      a fixed joint angle or posture. In this study we investigated the effect of hip
      and knee joint angles on neural activation within RF using multichannel surface
      electromyography (SEMG). METHODS: Eleven healthy men performed isometric maximal
      voluntary contraction (MVC) during knee extension and hip flexion at different
      hip or joint angles. During the contractions, SEMG of the RF was recorded using
      46 electrode pairs covering most of the superficial area of the muscle. RESULTS:
      During knee extension MVC, an increase in the hip joint angle was associated with
      a significant increase in SEMG amplitude in the proximal region and a decrease in
      the distal region (P < 0.05). Higher SEMG amplitude during hip flexion MVC
      compared with knee extension MVC was observed in proximal regions with the flexed
      knee and hip joint angles. This task-dependent spatial distribution of SEMG
      amplitude was seen at the extended hip, but not at the extended knee.
      CONCLUSIONS: SEMG amplitudes within the RF muscle are not modified uniformly with
      changes in joint position.

PMID- 24590733
TI  - Comparative study on effects of single and multiple oral administration of
      mungbean (Phaseolus radiatus L.) seed extract on the pharmacokinetics of
      aconitine by UHPLC-MS.
AB  - The study was aimed to investigate the effects of single and multiple oral
      administration of mungbean (Phaseolus radiatus L.) seed extract (ME) on the
      pharmacokinetics of aconitine in rats. The Sprague-Dawley rats were randomly
      divided into three groups (six rats each group). In group 1, rats were orally
      administered 500 ug/kg aconitine after receiving a single oral dose of 1 g/kg ME.
      In group 2, rats were orally administered with 500 ug/kg aconitine at day 7 of
      treatment with 1 g/kg/day ME. In group 3, rats were orally administered with 500
      ug/kg aconitine. Blood samples were collected at different time points (0.083,
      0.25, 0.5, 1.0, 1.5, 2.0, 4.0, 6.0, 8.0 and 10.0 h). The concentration of
      aconitine in rats plasma was determined by a fully validated ultra-high
      performance liquid chromatography coupled with mass spectrometry method. The
      results showed that single and multiple oral co-administration of ME
      significantly altered the pharmacokinetic parameters of aconitine.

PMID- 24590735
TI  - Capsule commentary on Hoffman et al., Brief training of student clinicians in
      shared decision making: a single-blind randomized control trial.

PMID- 24590736
TI  - Lead-time models should not be used to estimate overdiagnosis in cancer
      screening.
AB  - Lead-time can mean two different things: Clinical lead-time is the lead-time for
      clinically relevant tumors; that is, those that are not overdiagnosed. Model
      based lead-time is a theoretical construct where the time when the tumor would
      have caused symptoms is not limited by the person's death. It is the average time
      at which the diagnosis is brought forward for both clinically relevant and
      overdiagnosed cancers. When screening for breast cancer, clinical lead-time is
      about 1 year, while model-based lead-time varies from 2 to 7 years. There are two
      different methods to calculate overdiagnosis in cancer screening--the excess
      incidence approach and the lead-time approach--that rely on two different lead
      time definitions. Overdiagnosis when screening with mammography has varied from 0
      to 75 %. We have explained that these differences are mainly caused by using
      different definitions and methods and not by variations in data. High levels of
      overdiagnosis of cancer have usually been explained by detection of many slow
      growing tumors with long lead-times. This theory can be tested by studying if
      slow-growing tumors accumulate in the absence of screening, which they don't.
      Thus, it is likely that the natural history of many subclinical cancers is
      spontaneous regression.

PMID- 24590734
TI  - Comparative effectiveness of audit-feedback versus additional physician
      communication training to improve cancer screening for patients with limited
      health literacy.
AB  - BACKGROUND: We designed a continuing medical education (CME) program to teach
      primary care physicians (PCP) how to engage in cancer risk communication and
      shared decision making with patients who have limited health literacy (HL).
      OBJECTIVE: We evaluated whether training PCPs, in addition to audit-feedback,
      improves their communication behaviors and increases cancer screening among
      patients with limited HL to a greater extent than only providing clinical
      performance feedback. DESIGN: Four-year cluster randomized controlled trial.
      PARTICIPANTS: Eighteen PCPs and 168 patients with limited HL who were overdue for
      colorectal/breast/cervical cancer screening. INTERVENTIONS: Communication
      intervention PCPs received skills training that included standardized patient
      (SP) feedback on counseling behaviors. All PCPs underwent chart audits of
      patients' screening status semiannually up to 24 months and received two annual
      performance feedback reports. MAIN MEASURES: PCPs experienced three unannounced
      SP encounters during which SPs rated PCP communication behaviors. We examined
      between-group differences in changes in SP ratings and patient knowledge of
      cancer screening guidelines over 12 months; and changes in patient cancer
      screening rates over 24 months. KEY RESULTS: There were no group differences in
      SP ratings of physician communication at baseline. At follow-up, communication
      intervention PCPs were rated higher in general communication about cancer risks
      and shared decision making related to colorectal cancer screening compared to
      PCPs who only received performance feedback. Screening rates increased among
      patients of PCPs in both groups; however, there were no between-group differences
      in screening rates except for mammography. The communication intervention did not
      improve patient cancer screening knowledge. CONCLUSION: Compared to audit and
      feedback alone, including PCP communication training increases PCP patient
      centered counseling behaviors, but not cancer screening among patients with
      limited HL. Larger studies must be conducted to determine whether lack of changes
      in cancer screening were due to clinic/patient sample size versus ineffectiveness
      of communication training to change outcomes.

PMID- 24590737
TI  - Is implementation of the care transitions intervention associated with cost
      avoidance after hospital discharge?
AB  - BACKGROUND: Poorly-executed transitions out of the hospital contribute
      significant costs to the healthcare system. Several evidence-based interventions
      can reduce post-discharge utilization. OBJECTIVE: To evaluate the cost avoidance
      associated with implementation of the Care Transitions Intervention (CTI).
      DESIGN: A quasi-experimental cohort study using consecutive convenience sampling.
      PATIENTS: Fee-for-service Medicare beneficiaries hospitalized from 1 January 2009
      to 31 May 2011 in six Rhode Island hospitals. INTERVENTION: The CTI is a patient
      centered coaching intervention to empower individuals to better manage their
      health. It begins in-hospital and continues for 30 days, including one home visit
      and one to two phone calls. MAIN MEASURES: We examined post-discharge total
      utilization and costs for patients who received coaching (intervention group),
      who declined or were lost to follow-up (internal control group), and who were
      eligible, but not approached (external control group), using propensity score
      matching to control for baseline differences. KEY RESULTS: Compared to matched
      internal controls (N = 321), the intervention group had significantly lower
      utilization in the 6 months after discharge and lower mean total health care
      costs ($14,729 vs. $18,779, P = 0.03). The cost avoided per patient receiving the
      intervention was $3,752, compared to internal controls. Results for the external
      control group were similar. Shifting of costs to other utilization types was not
      observed. CONCLUSIONS: This analysis demonstrates that the CTI generates
      meaningful cost avoidance for at least 6 months post-hospitalization, and also
      provides useful metrics to evaluate the impact and cost avoidance of hospital
      readmission reduction programs.

PMID- 24590738
TI  - Identification of a novel nonsynonymous mutation of EYA1 disrupting splice site
      in a Korean patient with BOR syndrome.
AB  - The EYA1 gene is known as the causative gene of BOR (Branchio-oto-renal) syndrome
      which is a genetic disorder associated with branchial cleft cysts of fistulae,
      hearing loss, ear malformation, and renal anomalies. Although approximately 40%
      of patients with BOR syndrome have mutations in the EYA1 gene and over 130
      disease-causing mutations in EYA1 have been reported in various populations, only
      a few mutations have been reported in Korean families. In this study, genetic
      analysis of the EYA1 gene was performed in a Korean patient diagnosed with BOR
      syndrome and his parents. A de novo novel missense mutation, c.418G>A, located at
      the end of exon 6, changed glycine to serine at amino acid position 140 (p.G140S)
      and was suspected to affect normal splicing. Our in vitro splicing assay
      demonstrated that this mutation causes exon 6 skipping leading to frameshift and
      truncation of the protein to result in the loss of eyaHR. To the best of our
      knowledge, this is the first report revealing that a missense mutation in the
      exon disturbs normal splicing as a result of a substitution of the last
      nucleotide of an exon in EYA1.

PMID- 24590739
TI  - Cloning and molecular characterization of phospholipase D (PLD) delta gene from
      longan (Dimocarpus longan Lour.).
AB  - Longan (Dimocarpus longan Lour.) is a non-climacteric fruit with a short
      postharvest life. The regulation of phospholipase D (PLD) activity closely
      relates to postharvest browning and senescence of longan fruit. In this study, a
      novel cDNA clone of longan PLDdelta (LgPLDdelta) was obtained and registered in
      GenBank (accession No. JF791814). The deduced amino acid sequence possessed all
      of the three typical domains of plant PLDs, a C2 domain and two catalytic
      HxKxxxxD motifs. The tertiary structure of LgPLDdelta was further predicted. The
      western blot result showed that the LgPLDdelta protein was specifically
      recognized by PLDdelta antibody. The Q-RT-PCR (real-time quantitative PCR) result
      showed that the level of LgPLDdelta mRNA expression was higher in senescent
      tissues than in developing tissues, which was also high in postharvest fruit. The
      western-blotting result further certified the different expression of LgPLDdelta.
      These results provided a scientific basis for further investigating the mechanism
      of postharvest longan fruit adapting to environmental stress. 

PMID- 24590740
TI  - Genetic analysis of an F2 intercross between two strains of Japanese quail
      provided evidence for quantitative trait loci affecting carcass composition and
      internal organs.
AB  - The purpose of this study was to identify genomic regions, quantitative trait
      loci (QTL), affecting carcass traits on chromosome 1 in an F2 population of
      Japanese quail. For this purpose, two white and wild strains of Japanese quail
      (16 birds) were crossed reciprocally and F1 generation (34 birds) was created.
      The F2 generation was produced by intercrossing of the F1 birds. Phenotypic data
      including carcass weight, internal organs and carcass parts were collected on F2
      animals (422 birds). The total mapping population (472 birds) was genotyped for 8
      microsatellite markers on chromosome 1. QTL analysis was performed with interval
      mapping method applying the line-cross model. Significant QTL were identified for
      breast weight at 0 (P < 0.01), 172 (P < 0.05) and 206 (P < 0.01), carcass weight
      at 91 (P < 0.05), carcass fatness at 0 (P < 0.01), pre-stomach weight at 206 (P <
      0.01) and uropygial weight gland at 197 (P < 0.01) cM on chromosome 1. There was
      also evidence for imprinted QTL affecting breast weight (P < 0.01) on chromosome
      1. The proportion of the F2 phenotypic variation explained by the significant
      additive, dominance and imprinted QTL effects ranged from 1.0 to 7.3%, 1.2 to
      3.3% and 1.4 to 2.2%, respectively.

PMID- 24590741
TI  - Microfluidic direct writer with integrated declogging mechanism for fabricating
      cell-laden hydrogel constructs.
AB  - Cell distribution and nutrient supply in 3D cell-laden hydrogel scaffolds are
      critical and should mimic the in vivo cellular environment, but been difficult to
      control with conventional fabrication methods. Here, we present a microfluidic
      direct writer (MFDW) to construct 3D cell-laden hydrogel structures with openings
      permitting media exchange. The MFDW comprises a monolithic microfluidic head,
      which delivers coaxial streams of cell-laden sodium alginate and calcium chloride
      solutions to form hydrogel fibers. Fiber diameter is controlled by adjusting the
      ratio of the volumetric flow rates. The MFDW head is mounted on a motorized
      stage, which is automatically controlled and moves at a speed synchronized with
      the speed of fiber fabrication. Head geometry, flow rates, and viscosity of the
      writing solutions were optimized to prevent the occurrence of curling and
      bulging. For continuous use, a highly reliable process is needed, which was
      accomplished with the integration of a declogging conduit supplying a solvent to
      dissolve the clogging gel. The MFDW was used for layer-by-layer fabrication of
      simple 3D structures with encapsulated cells. Assembly of 3D structures with
      distinct fibers is demonstrated by alternatively delivering two different
      alginate gel solutions. The MFDW head can be built rapidly and easily, and will
      allow 3D constructs for tissue engineering to be fabricated with multiple
      hydrogels and cell types. 

PMID- 24590743
TI  - Why is it so hard to believe that media influence children and adolescents?

PMID- 24590744
TI  - Supplemental nutrition assistance program participation and child food security.
AB  - OBJECTIVE: This article investigates the association between Supplemental
      Nutrition Assistance Program (SNAP) participation and child food security by
      using data from the largest national survey of the food security of SNAP
      participants to date. METHODS: The analysis used a survey of nearly 3000
      households with children and a quasi-experimental research design that consisted
      of 2 sets of comparisons. Using a cross-sectional sample, we compared information
      collected from SNAP households within days of program entry with information
      collected from a contemporaneous sample of SNAP households that had participated
      for ~6 months. Next, by using a longitudinal sample, we compared baseline
      information collected from new-entrant SNAP households with information from
      those same households 6 months later. Multivariate logistic regression analysis
      was used to estimate associations between SNAP and child food security. RESULTS:
      SNAP participation was associated with an approximately one-third decrease in the
      odds of children being food insecure in both samples. In the cross-sectional
      analysis only, SNAP was also associated with a decrease in the odds of children
      experiencing severe food insecurity (designated very low food security). Findings
      were qualitatively robust to different empirical specifications. CONCLUSIONS:
      After controlling for other possible confounders, we found children in households
      that had participated in SNAP for 6 months experienced improvements in food
      security. On the basis of these findings, we conclude SNAP serves a vital role in
      improving the health and well-being of low-income children by increasing food
      security. Future research is needed to determine whether specific groups of
      children experience differential improvements in food security.

PMID- 24590745
TI  - Thirdhand smoke beliefs of parents.
AB  - OBJECTIVE: To determine if the belief that thirdhand smoke is harmful to children
      is associated with smoking parents' attitudes, home or car smoking policies, and
      quitting behaviors. METHODS: Data from a national randomized controlled trial,
      Clinical Effort Against Secondhand Smoke Exposure, assessed thirdhand smoke
      beliefs of 1947 smoking parents in an exit survey after a pediatric office visit
      in 10 intervention and 10 control practices. Twelve-month follow-up data were
      collected from 1355 parents. Multivariable logistic regression determined whether
      belief that thirdhand smoke harms the health of children is independently
      associated with parental behaviors and attitudes 12 months later. A chi(2) test
      assessed whether parents who disagreed that thirdhand smoke is harmful were more
      likely to make a quit attempt if they later believed that thirdhand smoke is
      harmful. RESULTS: Belief at the exit survey that thirdhand smoke is harmful was
      independently associated with having a strictly enforced smoke-free home policy
      (adjusted odds ratio: 2.05; 95% CI: 1.37-3.05) and car policy (adjusted odds
      ratio: 1.69; 95% CI: 1.04-2.74) at the 12-month follow-up. A significantly higher
      percentage (71% vs 50%) of parents who did not hold the thirdhand smoke harm
      belief at baseline made at least 1 quit attempt if they agreed that thirdhand
      smoke is harmful at the 12-month follow-up (P = .02). CONCLUSIONS: Thirdhand
      smoke harm belief was associated with a strictly enforced smoke-free home and car
      and attempts to quit smoking. Sensitizing parents to thirdhand smoke risk could
      facilitate beneficial tobacco control outcomes.

PMID- 24590746
TI  - Ultrasonography/MRI versus CT for diagnosing appendicitis.
AB  - BACKGROUND: Cross-sectional imaging increases accuracy in diagnosing
      appendicitis. We hypothesized that a radiation-free imaging pathway of
      ultrasonography selectively followed by MRI would not change clinical end points
      compared with computed tomography (CT) for diagnosis of acute appendicitis in
      children. METHODS: We retrospectively reviewed children (<18 years old) who had
      diagnostic imaging for suspected acute appendicitis between November 2008 and
      October 2012. Before November 2010 CT was used as the primary imaging modality
      (group A); subsequently, ultrasonography was the primary imaging modality
      followed by MRI for equivocal findings (group B). Data collected included time
      from triage to imaging and treatment and results of imaging and pathology.
      RESULTS: Six hundred sixty-two patients had imaging for suspected appendicitis
      (group A = 265; group B = 397, of which 136 [51%] and 161 [41%], respectively,
      had positive imaging for appendicitis). Negative appendectomy rate was 2.5% for
      group A and 1.4% for group B. Perforation rate was similar for both groups. Time
      from triage to antibiotic administration and operation did not differ between
      groups A and B. There was higher proportion of positive imaging and
      appendectomies in group A and thus more negative imaging tests in group B
      (ultrasonography and MRI), but diagnostic accuracy of the 2 imaging pathways was
      similar. CONCLUSIONS: In children with suspected acute appendicitis, a radiation
      free diagnostic imaging of ultrasonography selectively followed by MRI is
      feasible and comparable to CT, with no difference in time to antibiotic
      administration, time to appendectomy, negative appendectomy rate, perforation
      rate, or length of stay.

PMID- 24590747
TI  - Incidence and consequences of neonatal alloimmune thrombocytopenia: a systematic
      review.
AB  - BACKGROUND: Neonatal alloimmune thrombocytopenia (NAIT) is a potentially
      devastating disease that may lead to intracranial hemorrhage in the fetus or
      neonate, often with death or major neurologic damage. There are no routine
      screening programs for NAIT, preventive measures are taken only in a subsequent
      pregnancy. To estimate the population incidence of NAIT and its consequences, we
      conducted a review of the literature. Our results may aid in the design of a
      screening program. METHODS: An electronic literature search included Medline,
      Embase, Cochrane database and references of retrieved articles. Eligible for
      inclusion were all prospective studies aimed at diagnosing NAIT in a general,
      nonselected newborn population, with sufficient information on platelet count at
      birth, bleeding complications, and treatment. Titles and abstracts were reviewed,
      followed by review of full text publications. Studies were independently assessed
      by 2 reviewers for methodologic quality. Disagreements were resolved by
      consensus, including a third reviewer. RESULTS: From the initial 768 studies, 21
      remained for full text analysis, 6 of which met the inclusion criteria. In total,
      59,425 newborns were screened, with severe thrombocytopenia in 89 cases (0.15%).
      NAIT was diagnosed in 24 of these 89 newborns (27%). In 6 (25%) of these cases,
      an intracranial hemorrhage was found, all likely of antenatal origin.
      CONCLUSIONS: NAIT is among the most important causes of neonatal
      thrombocytopenia. Intracranial hemorrhage due to NAIT occurs in 10 per 100 000
      neonates, commonly before birth. Screening for NAIT might be effective but should
      be done antenatally.

PMID- 24590748
TI  - Clostridium difficile infection among children across diverse US geographic
      locations.
AB  - OBJECTIVE: Little is known about the epidemiology of Clostridium difficile
      infection (CDI) among children, particularly children <=3 years of age in whom
      colonization is common but pathogenicity uncertain. We sought to describe
      pediatric CDI incidence, clinical presentation, and outcomes across age groups.
      METHODS: Data from an active population- and laboratory-based CDI surveillance in
      10 US geographic areas during 2010-2011 were used to identify cases (ie,
      residents with C difficile-positive stool without a positive test in the previous
      8 weeks). Community-associated (CA) cases had stool collected as outpatients or
      <=3 days after hospital admission and no overnight health care facility stay in
      the previous 12 weeks. A convenience sample of CA cases were interviewed.
      Demographic, exposure, and clinical data for cases aged 1 to 17 years were
      compared across 4 age groups: 1 year, 2 to 3 years, 4 to 9 years, and 10 to 17
      years. RESULTS: Of 944 pediatric CDI cases identified, 71% were CA. CDI incidence
      per 100,000 children was highest among 1-year-old (66.3) and white (23.9) cases.
      The proportion of cases with documented diarrhea (72%) or severe disease (8%) was
      similar across age groups; no cases died. Among the 84 cases interviewed who
      reported diarrhea on the day of stool collection, 73% received antibiotics during
      the previous 12 weeks. CONCLUSIONS: Similar disease severity across age groups
      suggests an etiologic role for C difficile in the high rates of CDI observed in
      younger children. Prevention efforts to reduce unnecessary antimicrobial use
      among young children in outpatient settings should be prioritized.

PMID- 24590749
TI  - BMI, health behaviors, and quality of life in children and adolescents: a school
      based study.
AB  - OBJECTIVE: To explore the relationship between weight status (BMI) and health
      related quality of life in children and adolescents through application of the
      Child Health Utility 9D, a new generic preference-based instrument. METHODS: Data
      were collected from primary and high school students in rural and metropolitan
      regions of South Australia. Consenting participants (2588 in grades 4-6 and 765
      in grades 9-10) were weighed and measured and categorized as underweight, healthy
      weight, overweight, or obese according to International Obesity Taskforce BMI
      cutoff points (primary outcome). Participants also completed a questionnaire
      including the Child Health Utility 9D and standardized measures of physical
      activity, sedentary behavior, sleep patterns, and eating behavior (secondary
      outcomes). Descriptive and multivariate linear regression analyses were
      undertaken to calculate mean utility differences. RESULTS: In comparison with
      healthy-weight primary school students, adjusted mean utilities were lower for
      overweight (-0.016, P = .02) or obese (-0.039, P = .001) students. For high
      school students, the adjusted mean utilities were also lower for overweight and
      obese students but were nonsignificant (-0.018, P > .10). Physical activity,
      sedentary behavior, sleep patterns, and eating behavior were all found to be
      significantly associated with utilities. CONCLUSIONS: Irrespective of BMI, young
      people engaging in more physical activities or less sedentary behavior, and
      having healthier sleep patterns or eating behavior exhibited higher utilities.
      Associations between utilities and sleep patterns or eating behavior were
      stronger than the associations with BMI. Future economic evaluations for obesity
      interventions should more formally investigate the relationship between changes
      over time in weight status and health-related quality of life for children and
      adolescents.

PMID- 24590750
TI  - Economic evaluation of the routine childhood immunization program in the United
      States, 2009.
AB  - OBJECTIVES: To evaluate the economic impact of the 2009 routine US childhood
      immunization schedule, including diphtheria and tetanus toxoids and acellular
      pertussis, Haemophilus influenzae type b conjugate, inactivated poliovirus,
      measles/mumps/rubella, hepatitis B, varicella, 7-valent pneumococcal conjugate,
      hepatitis A, and rotavirus vaccines; influenza vaccine was not included. METHODS:
      Decision analysis was conducted using population-based vaccination coverage,
      published vaccine efficacies, historical data on disease incidence before
      vaccination, and disease incidence reported during 2005 to 2009. Costs were
      estimated using the direct cost and societal (direct and indirect costs)
      perspectives. Program costs included vaccine, administration, vaccine-associated
      adverse events, and parent travel and work time lost. All costs were inflated to
      2009 dollars, and all costs and benefits in the future were discounted at a 3%
      annual rate. A hypothetical 2009 US birth cohort of 4,261,494 infants over their
      lifetime was followed up from birth through death. Net present value (net
      savings) and benefit-cost ratios of routine childhood immunization were
      calculated. RESULTS: Analyses showed that routine childhood immunization among
      members of the 2009 US birth cohort will prevent ~42,000 early deaths and 20
      million cases of disease, with net savings of $13.5 billion in direct costs and
      $68.8 billion in total societal costs, respectively. The direct and societal
      benefit-cost ratios for routine childhood vaccination with these 9 vaccines were
      3.0 and 10.1. CONCLUSIONS: From both direct cost and societal perspectives,
      vaccinating children as recommended with these vaccines results in substantial
      cost savings.

PMID- 24590751
TI  - Effective messages in vaccine promotion: a randomized trial.
AB  - OBJECTIVES: To test the effectiveness of messages designed to reduce vaccine
      misperceptions and increase vaccination rates for measles-mumps-rubella (MMR).
      METHODS: A Web-based nationally representative 2-wave survey experiment was
      conducted with 1759 parents age 18 years and older residing in the United States
      who have children in their household age 17 years or younger (conducted June-July
      2011). Parents were randomly assigned to receive 1 of 4 interventions: (1)
      information explaining the lack of evidence that MMR causes autism from the
      Centers for Disease Control and Prevention; (2) textual information about the
      dangers of the diseases prevented by MMR from the Vaccine Information Statement;
      (3) images of children who have diseases prevented by the MMR vaccine; (4) a
      dramatic narrative about an infant who almost died of measles from a Centers for
      Disease Control and Prevention fact sheet; or to a control group. RESULTS: None
      of the interventions increased parental intent to vaccinate a future child.
      Refuting claims of an MMR/autism link successfully reduced misperceptions that
      vaccines cause autism but nonetheless decreased intent to vaccinate among parents
      who had the least favorable vaccine attitudes. In addition, images of sick
      children increased expressed belief in a vaccine/autism link and a dramatic
      narrative about an infant in danger increased self-reported belief in serious
      vaccine side effects. CONCLUSIONS: Current public health communications about
      vaccines may not be effective. For some parents, they may actually increase
      misperceptions or reduce vaccination intention. Attempts to increase concerns
      about communicable diseases or correct false claims about vaccines may be
      especially likely to be counterproductive. More study of pro-vaccine messaging is
      needed.

PMID- 24590752
TI  - Prenatal nutrient supplementation and postnatal growth in a developing nation: an
      RCT.
AB  - BACKGROUND AND OBJECTIVES: Prenatal lipid-based nutrient supplements (LNS) have
      been shown to improve birth anthropometry. However, little is known about the
      effects of such supplements on infant health. We hypothesized that prenatal LNS
      compared with multiple micronutrient supplement for pregnant and lactating women
      would improve survival, growth, and morbidity during infancy. METHODS: Infants'
      weight, length, head, chest, and mid-upper arm circumferences were measured
      during monthly home visits from birth to 12 months of age in the Micronutriments
      et Sante de la Mere et de l'Enfant--2 trial. Differences in stunting and wasting
      episodes between study arms were assessed by Cox regression for recurrent event
      models. Morbidity signs during the 2 weeks before the visits and death cases were
      also assessed by multilevel analysis accounting for repeated individual
      measurements. RESULTS: Infant length-for-age growth (-0.033 z score/month; 95%
      confidence interval: -0.601 to -0.006; P = .018) for the LNS group was inferior
      to that of the control group. We did not find evidence of significant difference
      in mortality or morbidity between groups. CONCLUSIONS: The previously reported
      positive effect of prenatal LNS on birth length was not sustained during the
      postnatal phase. Prenatal LNS does not appear to make a long-lasting difference
      in child linear growth.

PMID- 24590753
TI  - Infant sleep machines and hazardous sound pressure levels.
AB  - BACKGROUND AND OBJECTIVE: Infant "sleep machines" (ISMs) produce ambient noise or
      noise to mask other sounds in an infant's room with the goal of increasing
      uninterrupted sleep. We suggest that the consistent use of these devices raises
      concerns for increasing an infant's risk of noise-induced hearing loss. We
      therefore sought to determine the maximum output levels of these sleep machines.
      METHODS: Sound levels of 14 ISMs played at maximum volume were measured at 30,
      100, and 200 cm from the machine using correction factors to account for a 6
      month-old's ear canal. RESULTS: Maximum sound levels at 30 cm were >50 A-weighted
      dB for all devices, which is the current recommended noise limit for infants in
      hospital nurseries. Three machines produced output levels >85 A-weighted dB,
      which, if played at these levels for >8 hours, exceeds current occupational
      limits for accumulated noise exposure in adults and risks noise-induced hearing
      loss. CONCLUSIONS: ISMs are capable of producing output sound pressure levels
      that may be damaging to infant hearing and auditory development. We outline
      recommendations for safer operation of these machines.

PMID- 24590754
TI  - Australian Bat Lyssavirus in a child: the first reported case.
AB  - Human infection with Australian Bat Lyssavirus is extremely rare and has not
      previously been reported in a child. We describe a fatal case of Australian Bat
      Lyssavirus in an 8-year-old child, and review the literature pertaining to the
      diagnosis and management of lyssavirus infection with consideration of its
      applicability to this emerging strain. 

PMID- 24590755
TI  - Cross-coupling reaction of saccharide-based alkenyl boronic acids with aryl
      halides: the synthesis of bergenin.
AB  - A convenient synthetic pathway enabling D-glucal and D-galactal pinacol boronates
      to be prepared in good isolated yields was achieved. Both pinacol boronates were
      tested in a series of cross-coupling reactions under Suzuki-Miyaura cross
      coupling conditions to obtain the corresponding aryl, heteroaryl, and alkenyl
      derivatives in high isolated yields. This methodology was applied to the formal
      synthesis of the glucopyranoside moiety of papulacandin D and the first total
      synthesis of bergenin. 

PMID- 24590756
TI  - Outcomes of intensity-modulated radiotherapy versus conventional radiotherapy for
      hypopharyngeal cancer.
AB  - BACKGROUND: The purpose of this study was to discuss if the adoption of intensity
      modulated radiotherapy (IMRT) for hypopharyngeal squamous cell carcinoma (SCC)
      has improved the outcome. METHODS: We compared 3-dimensional (3D) radiotherapy
      (RT) and IMRT in all patients with hypopharyngeal SCC treated with curative
      intent RT or chemoradiation therapy (CRT) from January 1, 2000, to February 28,
      2010. Locoregional control, overall survival (OS), distant relapse rate, larynx
      preservation rate, and enteral feeding tube duration were analyzed. RESULTS: Of
      181 consecutive patients, 90 received 3D-RT and 91 received IMRT. At 3 years, the
      IMRT group had higher locoregional control compared with the 3D-RT group (75% vs
      58%; p = .003), but similar OS (50% vs 52%; p = .99), distant relapse rate (23%
      vs 20%; p = .79), and larynx-preservation rate (90% vs 86%; p = .16). The 2-year
      enteral feeding tube dependency rate was similar in both groups (19% vs 18%; p =
      .12). CONCLUSION: Patients with hypopharyngeal SCC treated with IMRT showed a
      higher locoregional control compared with 3D-RT. However, distant-relapse rate
      and OS remain comparable between treatment techniques.

PMID- 24590757
TI  - Control of thrombotic thrombocytopenic purpura by sirolimus in a child with
      juvenile myelomonocytic leukemia and somatic N-RAS mutation.
AB  - We describe an infant who developed juvenile myelomonocytic leukemia (JMML) at
      the age of 6 months. Myeloproliferation was effectively controlled by low-dose
      cytosine arabinoside and 13-cis retinoic acid therapy. Two years after therapy
      for JMML was stopped, at the age of 5 years, the patient developed autoimmune
      thrombotic thrombocytopenic purpura (TTP). TTP was transiently controlled by
      plasma exchange, prednisolone, rituximab, and cyclophosphamide, but relapsed
      within a short time. Long-term control of TTP was established by sirolimus.
      Somatic N-RAS G38A->Gly13Asp substitution was restricted to hematopoietic cells.
      The somatic N-RAS mutation may link myeloproliferation and autoimmunity.

PMID- 24590758
TI  - HPLC-fluorescence method for the enantioselective analysis of propranolol in rat
      serum using immobilized polysaccharide-based chiral stationary phase.
AB  - A stereoselective high-performance liquid chromatographic (HPLC) method was
      developed and validated to determine S-(-)- and R-(+)-propranolol in rat serum.
      Enantiomeric resolution was achieved on cellulose tris(3,5
      dimethylphenylcarbamate) immobilized onto spherical porous silica chiral
      stationary phase (CSP) known as Chiralpak IB. A simple analytical method was
      validated using a mobile phase consisted of n-hexane-ethanol-triethylamine
      (95:5:0.4%, v/v/v) at a flow rate of 0.6 mL min(-1) and fluorescence detection
      set at excitation/emission wavelengths 290/375 nm. The calibration curves were
      linear over the range of 10-400 ng mL(-1) (R = 0.999) for each enantiomer with a
      detection limit of 3 ng mL(-1). The proposed method was validated in compliance
      with ICH guidelines in terms of linearity, accuracy, precision, limits of
      detection and quantitation, and other aspects of analytical validation. Actual
      quantification could be made for propranolol isomers in serum obtained from rats
      that had been intraperitoneally (i.p.) administered a single dose of the drug.
      The proposed method established in this study is simple and sensitive enough to
      be adopted in the fields of clinical and forensic toxicology. Molecular modeling
      studies including energy minimization and docking studies were first performed to
      illustrate the mechanism by which the active enantiomer binds to the beta
      adrenergic receptor and second to find a suitable interpretation of how both
      enantiomers are interacting with cellulose tris(3,5-dimethylphenylcarbamate) CSP
      during the process of resolution. The latter interaction was demonstrated by
      calculating the binding affinities and interaction distances between propranolol
      enantiomers and chiral selector.

PMID- 24590759
TI  - Implications of utilization shifts on medical-care price measurement.
AB  - The medical-care sector often experiences changes in medical protocols and
      technologies that cause shifts in treatments. However, the commonly used medical
      care price indexes reported by the Bureau of Labor Statistics hold the mix of
      medical services fixed. In contrast, episode expenditure indexes, advocated by
      many health economists, track the full cost of disease treatment, even as
      treatments shift across service categories (e.g., inpatient to outpatient
      hospital). In our data, we find that these two conceptually different measures of
      price growth show similar aggregate rates of inflation over the 2003-2007 period.
      Although aggregate trends are similar, we observe differences when looking at
      specific disease categories.

PMID- 24590760
TI  - The rubber hand illusion increases heat pain threshold.
AB  - BACKGROUND: Accumulating evidence shows that manipulations of cortical body
      representation, for example, by simply viewing one's own body, can relieve pain
      in healthy subjects. Despite the widespread use of the rubber hand illusion (RHI)
      as an effective experimental tool for the manipulation of bodily awareness,
      previous studies examining the analgesic effect of the RHI have produced
      conflicting results. METHOD: We used noxious heat stimuli to induce finger pain
      in 29 healthy subjects, and we recorded the participants' pain thresholds and
      subjective pain ratings during the RHI and during the control conditions. Two
      control conditions were included in our experiment - a standard one with reduced
      illusion strength (asynchronous stroking control) and an additional one in which
      the participants viewed their own hand. RESULTS: Raw data showed that both the
      RHI and the vision of the own hand resulted in slightly higher pain thresholds
      than the asynchronous stroking control (illusion: 47.79  degrees C; own-hand:
      47.99  degrees C; asynchronous: 47.52  degrees C). After logarithmic
      transformation to achieve normality, paired t-tests revealed that both increases
      in pain threshold were significant (illusion/asynchronous: p = 0.036; own
      hand/asynchronous: p = 0.007). In contrast, there was no significant difference
      in pain threshold between the illusion and the own-hand conditions (p = 0.656).
      Pain rating scores were not log-normal, and Wilcoxon singed-rank tests found no
      significant differences in pain ratings between the study conditions. CONCLUSION:
      The RHI increases heat pain threshold and the analgesic effect of the RHI is
      comparable with that of seeing one's own hand. The latter finding may have
      clinical implications.

PMID- 24590761
TI  - A uniformly oriented MFI membrane for improved CO2 separation.
AB  - Membrane separation of CO2 from natural gas, biogas, synthesis gas, and flu gas
      is a simple and energy-efficient alternative to other separation techniques. But
      results for CO2 -selective permeance have always been achieved by randomly
      oriented and thick zeolite membranes. Thin, oriented membranes have great
      potential to realize high-flux and high-selectivity separation of mixtures at low
      energy cost. We now report a facile method for preparing silica MFI membranes in
      fluoride media on a graded alumina support. In the resulting membrane straight
      channels are uniformly vertically aligned and the membrane has a thickness of 0.5
      MUm. The membrane showed a separation selectivity of 109 for CO2/H2 mixtures and
      a CO2 permeance of 51*10(-7) mol m(-2) s(-1) Pa(-1) at -35  degrees C, making it
      promising for practical CO2 separation from mixtures.

PMID- 24590762
TI  - Evidence of a common mechanism of disassembly of adherens junctions through
      Galpha13 targeting of VE-cadherin.
AB  - The heterotrimeric G protein Galpha13 transduces signals from G protein-coupled
      receptors (GPCRs) to induce cell spreading, differentiation, migration, and cell
      polarity. Here, we describe a novel GPCR-independent function of Galpha13 in
      regulating the stability of endothelial cell adherens junctions (AJs). We
      observed that the oxidant H2O2, which is released in response to multiple
      proinflammatory mediators, induced the interaction of Galpha13 with VE-cadherin.
      Galpha13 binding to VE-cadherin in turn induced Src activation and VE-cadherin
      phosphorylation at Tyr 658, the p120-catenin binding site thought to be
      responsible for VE-cadherin internalization. Inhibition of Galpha13-VE-cadherin
      interaction using an interfering peptide derived from the Galpha13 binding motif
      on VE-cadherin abrogated the disruption of AJs in response to inflammatory
      mediators. These studies identify a unique role of Galpha13 binding to VE
      cadherin in mediating VE-cadherin internalization and endothelial barrier
      disruption and inflammation.

PMID- 24590763
TI  - Interplay of host microbiota, genetic perturbations, and inflammation promotes
      local development of intestinal neoplasms in mice.
AB  - The preferential localization of some neoplasms, such as serrated polyps (SPs),
      in specific areas of the intestine suggests that nongenetic factors may be
      important for their development. To test this hypothesis, we took advantage of
      transgenic mice that expressed HB-EGF throughout the intestine but developed SPs
      only in the cecum. Here we show that a host-specific microbiome was associated
      with SPs and that alterations of the microbiota induced by antibiotic treatment
      or by embryo transfer rederivation markedly inhibited the formation of SPs in the
      cecum. Mechanistically, development of SPs was associated with a local decrease
      in epithelial barrier function, bacterial invasion, production of antimicrobials,
      and increased expression of several inflammatory factors such as IL-17, Cxcl2,
      Tnf-alpha, and IL-1. Increased numbers of neutrophils were found within the SPs,
      and their depletion significantly reduced polyp growth. Together these results
      indicate that nongenetic factors contribute to the development of SPs and suggest
      that the development of these intestinal neoplasms in the cecum is driven by the
      interplay between genetic changes in the host, an inflammatory response, and a
      host-specific microbiota.

PMID- 24590764
TI  - Follicular regulatory T cells control humoral autoimmunity via NFAT2-regulated
      CXCR5 expression.
AB  - Maturation of high-affinity B lymphocytes is precisely controlled during the
      germinal center reaction. This is dependent on CD4(+)CXCR5(+) follicular helper T
      cells (TFH) and inhibited by CD4(+)CXCR5(+)Foxp3(+) follicular regulatory T cells
      (TFR). Because NFAT2 was found to be highly expressed and activated in follicular
      T cells, we addressed its function herein. Unexpectedly, ablation of NFAT2 in T
      cells caused an augmented GC reaction upon immunization. Consistently, however,
      TFR cells were clearly reduced in the follicular T cell population due to
      impaired homing to B cell follicles. This was TFR-intrinsic because only in these
      cells NFAT2 was essential to up-regulate CXCR5. The physiological relevance for
      humoral (auto-)immunity was corroborated by exacerbated lupuslike disease in the
      presence of NFAT2-deficient TFR cells. 

PMID- 24590765
TI  - Blimp-1 represses CD8 T cell expression of PD-1 using a feed-forward
      transcriptional circuit during acute viral infection.
AB  - Programmed cell death 1 (PD-1) is an inhibitory immune receptor that regulates T
      cell function, yet the molecular events that control its expression are largely
      unknown. We show here that B lymphocyte-induced maturation protein 1 (Blimp-1)
      deficient CD8 T cells fail to repress PD-1 during the early stages of CD8 T cell
      differentiation after acute infection with lymphocytic choriomeningitis virus
      (LCMV) strain Armstrong. Blimp-1 represses PD-1 through a feed-forward repressive
      circuit by regulating PD-1 directly and by repressing NFATc1 expression, an
      activator of PD-1 expression. Blimp-1 binding induces a repressive chromatin
      structure at the PD-1 locus, leading to the eviction of NFATc1 from its site.
      These data place Blimp-1 at an important phase of the CD8 T cell effector
      response and provide a molecular mechanism for its repression of PD-1.

PMID- 24590767
TI  - Sterically hindered phthalocyanines for dye-sensitized solar cells: influence of
      the distance between the aromatic core and the anchoring group.
AB  - A new phthalocyanine (Pc) bearing bulky peripheral substituents and a carboxylic
      anchoring group directly attached to the macrocycle has been prepared and used as
      a sensitizer in DSSCs, reaching 5.57% power conversion efficiency. In addition,
      an enhanced performance for the TT40 dye, previously reported by us, was achieved
      in optimized devices, obtaining a new record efficiency with Pc-sensitized cells.

PMID- 24590768
TI  - Practical introduction of novel oral anticoagulants through an anticoagulation
      nurse. The Leeuwarden model.
AB  - INTRODUCTION: This paper describes the implementation of novel oral
      anticoagulants (NOACs) through an anticoagulation nurse. Logistics and tasks of
      this new function are described and preliminary data are presented. METHODS:
      Indications for NOACs are explained by the treating cardiologists. Thereafter,
      the patient is referred to the anticoagulation nurse before starting a NOAC.
      After providing a patient with information and checking the creatinine clearance,
      co-medication and medical history, a prescription for NOAC is made. RESULTS: In 3
      months, 51 patients were referred for NOAC therapy. Mean age was 68 years,
      CHA2DS2-VASc score was 2.9. Renal function was impaired in 28 %. Only 63 % of the
      patients had an uneventful start-up. NOAC therapy was withheld or prematurely
      stopped in 22 %. 30 % of patients needed a reduced NOAC dose. In 37 %, the
      anticoagulation nurse had extended patient contact, mainly because of (presumed)
      side effects. CONCLUSION: Given the number of interactions that were made using a
      separate patient contact through the anticoagulation nurse, this seems to be an
      important improvement in the quality of care and deserves further expansion.

PMID- 24590769
TI  - Unroofed coronary sinus newly diagnosed in adult patients after corrected
      congenital heart disease.
AB  - Patients with congenital heart disease corrected in early childhood may later in
      life present with cardiac symptoms caused by other associated congenital
      anomalies that were initially not diagnosed. Nowadays, several noninvasive
      imaging modalities are available for the visualisation of cardiac anatomy in
      great detail. We describe two patients with an unroofed coronary sinus, a rare
      congenital anomaly which could be diagnosed using a combination of modalities
      including echocardiography, cardiac CT and cardiac MRI. 

PMID- 24590766
TI  - The protein tyrosine phosphatase PTP1B is a negative regulator of CD40 and BAFF-R
      signaling and controls B cell autoimmunity.
AB  - Tyrosine phosphorylation of signaling molecules that mediate B cell activation in
      response to various stimuli is tightly regulated by protein tyrosine phosphatases
      (PTPs). PTP1B is a ubiquitously expressed tyrosine phosphatase with well
      characterized functions in metabolic signaling pathways. We show here that PTP1B
      negatively regulates CD40, B cell activating factor receptor (BAFF-R), and TLR4
      signaling in B cells. Specifically, PTP1B counteracts p38 mitogen-activated
      protein kinase (MAPK) activation by directly dephosphorylating Tyr(182) of this
      kinase. Mice with a B cell-specific PTP1B deficiency show increased T cell
      dependent immune responses and elevated total serum IgG. Furthermore, aged
      animals develop systemic autoimmunity with elevated serum anti-dsDNA, spontaneous
      germinal centers in the spleen, and deposition of IgG immune complexes and C3 in
      the kidney. In a clinical setting, we observed that B cells of rheumatoid
      arthritis patients have significantly reduced PTP1B expression. Our data suggest
      that PTP1B plays an important role in the control of B cell activation and the
      maintenance of immunological tolerance.

PMID- 24590770
TI  - Using genetic variation for establishing causality of cardiovascular risk
      factors: overcoming confounding and reverse causality.
AB  - Cardiovascular disease (CVD) remains the leading cause of death in developed
      countries, despite the decline of CVD mortality over the last two decades. From
      observational, predictive research, efforts have been made to find causal risk
      factors for CVD. However, in recent years, some of these findings have been shown
      to be mistaken. Possible explanations for the discrepant findings are confounding
      and reverse causation. Genetic epidemiology has tried to address these problems
      through the use of Mendelian randomisation. In this paper, we discuss the promise
      and limitations of using genetic variation for establishing causality of
      cardiovascular risk factors. 

PMID- 24590771
TI  - Think twice before you tell.

PMID- 24590772
TI  - Highly diastereoselective and regioselective copper-catalyzed nitrosoformate
      dearomatization reaction under aerobic-oxidation conditions.
AB  - An unprecedented copper-catalyzed acylnitroso dearomatization reaction, which
      expands the traditional acylnitroso ene reaction and acylnitroso Diels-Alder
      reaction to a new type of transformation, has been developed under aerobic
      oxidation. Intermolecular and intra-/intermolecular reaction modes demonstrate an
      entirely different N- or O-acylnitroso selectivity. Hence, we can utilize this
      reaction as a highly diastereoselective access to a series of new pyrroloindoline
      derivatives, which are important structural motifs for natural-product synthesis.

PMID- 24590773
TI  - Germline variants in the CYP19A1 gene are related to specific adverse events in
      aromatase inhibitor users: a substudy of Dutch patients in the TEAM trial.
AB  - Musculoskeletal adverse events (MSAEs) and vasomotor symptoms (VMSs) are known
      side-effects of aromatase inhibitors, and may be related to genetic variations of
      the aromatase gene (CYP19A1). We investigated the relationship between these
      specific AEs and single nucleotide polymorphisms (SNPs) in the CYP19A1 gene in
      postmenopausal, hormone receptor-positive early breast cancer (BC) patients
      treated with adjuvant exemestane for 5 years. Dutch patients who were randomized
      to receive 5 years of exemestane in the Tamoxifen Exemestane Adjuvant
      Multinational (TEAM) trial were included. A tagging-SNP approach was performed,
      covering 80 % of variations of the CYP19A1 gene with 30 SNPs. Logistic regression
      analyses were used to assess the risk of reporting VMSs or MSAEs in relation to
      genotypes within selected SNPs. Of 737 included patients, 281 patients reported
      at least one MSAE (n = 210) or VMS (n = 163). Homozygous AA genotype of rs934635
      was associated with a significantly higher odds of MSAEs (multivariate odds ratio
      (OR) 4.66, p = 0.008) and VMSs (multivariate OR 2.78, p = 0.044). Regarding both
      rs1694189 and rs7176005, the homozygous variant genotypes (TT) were associated
      with a higher odds of VMSs, but not MSAEs (OR 1.758, p = 0.025 and OR 6.361, p =
      0.021, respectively). Our exploratory analysis demonstrated that some CYP19A1
      gene variations may be associated with MSAEs and/or VMSs. Specifically, patients
      with the homozygous variant rs934635 genotype reported more MSAEs and VMSs.
      Although further confirmatory studies are warranted, genomic profiling can help
      identify patients at an increased risk of reporting these specific AEs,
      potentiating further personalized BC treatment.

PMID- 24590774
TI  - Detection and clinical relevance of hematogenous tumor cell dissemination in
      patients with ductal carcinoma in situ.
AB  - Hematogenous tumor cell dissemination is a crucial step in systemic disease
      progression and predicts reduced clinical outcome in breast cancer patients. Only
      invasive cancers are assumed to shed tumor cells into the bloodstream and
      infiltrate lymph nodes. However, recent studies revealed that disseminated tumor
      cells (DTCs) may be detected in bone marrow (BM) of patients with preinvasive
      lesions, i.e., ductal carcinoma in situ (DCIS). The purpose of this analysis was
      to examine the incidence and clinical value of DTC detection in a large series of
      patients with pure DCIS. 404 patients treated for DCIS at the University Hospital
      Tuebingen, Germany were included into this analysis. BM was analyzed by
      immunocytochemistry (pancytokeratin antibody A45-B/B3) using ACIS system
      (Chromavision) according to the ISHAGE evaluation criteria. Sentinel nodes were
      analyzed in 316 patients by step sectioning and hematoxylin-eosin staining. DTCs
      were detected in 63 of 404 patients (16 %). No correlation was observed between
      BM status and tumor size, grading, histology or Van Nuys prognostic index. In two
      cases, metastatic spread into lymph nodes was observed; isolated tumor cells were
      found in one patient. After a median follow-up of 45 months (range 3-131 months),
      3 % of BM positive patients died compared to 1 % of BM negative patients (p =
      0.254). Relapse of any kind was observed in 7 % of patients with DTCs vs. 5 % of
      patients without DTCs (p = 0.644). The differences in overall (p = 0.088) and
      disease-free survival (p = 0.982) calculated by log-rank test were not
      statistically significant. Tumor cell dissemination may be detected in patients
      diagnosed with DCIS. Whether these cells disseminate from real preinvasive
      mammary lesions or represent the earliest step of microinvasion, remains unclear.
      A longer follow-up may be necessary to accurately assess clinical value of these
      cells in DCIS patients.

PMID- 24590775
TI  - 3' end formation and regulation of eukaryotic mRNAs.
AB  - The polyadenosine (polyA) "tail" is an essential feature at the 3' end of nearly
      all eukaryotic mRNAs. This appendage has roles in many steps in the gene
      expression pathway and is subject to extensive regulation. Selection of
      alternative sites for polyA tail addition is a widely used mechanism to generate
      alternative mRNAs with distinct 3'UTRs that can be subject to distinct forms of
      posttranscriptional control. One such type of regulation includes cytoplasmic
      lengthening and shortening of the polyA tail, which is coupled to changes in mRNA
      translation and decay. Here we present a general overview of 3' end formation in
      the nucleus and regulation of the polyA tail in the cytoplasm, with an emphasis
      on the diverse roles of 3' end regulation in the control of gene expression in
      different biological systems. 

PMID- 24590776
TI  - Poly(A) polymerase-based poly(A) length assay.
AB  - mRNA polyadenylation functions in nuclear export, translation, and stability. We
      describe an efficient protocol designed to assess poly(A) tail length that is
      based on 3' tailing by yeast poly(A) polymerase and product analysis to single
      nucleotide resolution by capillary electrophoresis. 

PMID- 24590777
TI  - Using Klenow-mediated extension to measure poly(A)-tail length and position in
      the transcriptome.
AB  - The poly(A)-tail that terminates most mRNA and many noncoding RNA is a convenient
      "hook" to isolate mRNA. However the length of this tail and its position within
      the primary RNA transcript can also hold diagnostic value for RNA metabolism. In
      general, mRNA with a long poly(A)-tail is well translated, whereas a short
      poly(A)-tail can indicate translational silencing. A short poly(A)-tail is also
      appended to RNA-decay intermediates via the TRAMP complex. A number of approaches
      have been developed to measure the length and position of the poly(A)-tail. Here,
      we describe a simple method to "tag" adenylated RNA using the native function of
      DNA polymerase I to extend an RNA primer on a DNA template in second-strand DNA
      synthesis. This function can be harnessed as a means to purify, visualize, and
      quantitate poly(A)-dynamics of individual RNA and the transcriptome en masse. 

PMID- 24590778
TI  - Detection of uridylated mRNAs.
AB  - Uridine addition at the 3' end of RNAs (i.e., uridylation) emerges as a critical
      posttranscriptional modification promoting RNA degradation. Uridylation has been
      notably linked to the degradation of small RNAs, correlated with the 5'
      shortening of RISC-cleaved transcripts and the degradation of mRNAs. We describe
      here a method based on 3' RACE (3' Rapid Amplification of cDNA End) PCR that has
      been successfully used to investigate nucleotide addition at the 3' end of RISC
      cleaved transcripts and full-length mRNAs in plants.

PMID- 24590779
TI  - Cytoplasmic polyadenylation assays.
AB  - Basic research in Drosophila melanogaster has benefited from a plethora of
      powerful genetics tools. Detailed biochemical analysis, however, has often been
      difficult due to the lack of in vitro systems that faithfully recapitulate the
      observations made in vivo. In the field of posttranscriptional regulation, the
      recent establishment of robust in vitro systems from embryo and ovary material
      has fueled the mechanistic understanding of a variety of processes. Here we
      describe protocols to obtain and use extracts from Drosophila embryos that are
      competent for cytoplasmic polyadenylation and translation of exogenously added
      transcripts. 

PMID- 24590780
TI  - In vitro analysis of transcriptional activators and polyadenylation.
AB  - In vitro assays have provided a valuable tool to study the mechanism of 3'
      processing of eukaryotic mRNA precursors and have contributed a great deal to the
      identification of factors that carry out and regulate 3' processing. Previously,
      we have shown that transcriptional activators directly enhance polyadenylation by
      utilizing in vitro transcription-coupled polyadenylation with the prototypical
      transcription activator GAL4-VP16. In this chapter, we describe a detailed
      protocol for this assay, which will be useful in examining potential roles for
      other transcription-related factors in 3' processing and other questions related
      to the coupling of transcription and mRNA polyadenylation. 

PMID- 24590781
TI  - Fluorescence detection of polyadenylation reaction through the coordination of
      adenosine2-coralyne-adenosine2.
AB  - A simple, sensitive, and selective-detection system for polyadenylation reaction
      was developed based on the fact that coralyne induces conformational change of
      polyadenosine [poly(A)] oligonucleotide through adenosine2-coralyne-adenosine2
      coordination. Double-strand chelating dye SYBR Green I fluoresces weakly in the
      presence of random coil of poly(A). Coralyne enables poly(A) to change its
      conformation from a random coil to a folded structure, which leads to an
      increased fluorescence of SYBR Green I. When the 3' end of RNA is polyadenylated
      with poly(A) polymerase, coralyne-induced fluorescence enhancement of the poly(A)
      SYBR Green I complex is well suited for monitoring polyadenylation reaction.

PMID- 24590782
TI  - Small molecule recognition of poly(A).
AB  - The binding of small molecules to non-canonical nucleic acid structures has been
      a major focus of rational drug design. Among the non-canonical nucleic acid
      structures, targeting poly(A) using small molecules has attracted a special
      interest due to the cellular functions of poly(A) tails. Here, the methods for
      determining the binding of a small molecule to poly(A) using UV-visible(UV-Vis)
      and Circular Dichroism (CD) Spectroscopy are described. Experiments used in
      determining the melting temperature, binding stoichiometry and dissociation
      constant of poly(A)-small molecule systems are depicted.

PMID- 24590783
TI  - The stem-loop luciferase assay for polyadenylation (SLAP) method for determining
      CstF-64-dependent polyadenylation activity.
AB  - Polyadenylation is an essential cellular process in eukaryotic cells (Edmonds M
      and Abrams R, J Biol Chem 235, 1142-1149, 1960; Zhao J et al., Microbiol Mol Biol
      Rev 63, 405-445, 1999; Edmonds M, Progr Nucleic Acid Res Mol Biol 71, 285-389,
      2002). For this reason, it has been difficult to examine the functions of
      specific polyadenylation proteins in vivo. Here, we describe a cell culture assay
      that allows structure-function experiments on CstF-64, a protein that binds to
      pre-mRNAs downstream of the cleavage site for accurate and efficient
      polyadenylation. We also demonstrate that the stem-loop luciferase assay for
      polyadenylation (SLAP) accurately reflects CstF-64-dependent polyadenylation.
      This assay could be easily adapted to the study of other important RNA-binding
      proteins in polyadenylation.

PMID- 24590784
TI  - Accurate mapping of cleavage and polyadenylation sites by 3' region extraction
      and deep sequencing.
AB  - Deep sequencing of RNA (RNA-seq) is becoming a standard method to study gene
      expression. While RNA-seq reads cover most regions of an mRNA sequence, they are
      often depleted in the 3' end region, making them less amenable for mapping the
      cleavage and polyadenylation site (pA). A major problem in identification of pA
      is mispriming at internal A-rich regions and oligo(A) tails when an oligo(dT)
      primer is used for reverse transcription or sequencing. We recently developed a
      method named 3' region extraction and deep sequencing (3'READS), which completely
      addresses mispriming issues and is straightforward to use. The method accurately
      maps pAs and allows quantitative analysis of alternative cleavage and
      polyadenylation (APA) isoforms and gene expression.

PMID- 24590785
TI  - Polyadenylation site prediction using PolyA-iEP method.
AB  - This chapter presents a method called PolyA-iEP that has been developed for the
      prediction of polyadenylation sites. More precisely, PolyA-iEP is a method that
      recognizes mRNA 3'ends which contain polyadenylation sites. It is a modular
      system which consists of two main components. The first exploits the advantages
      of emerging patterns and the second is a distance-based scoring method. The
      outputs of the two components are finally combined by a classifier. The final
      results reach very high scores of sensitivity and specificity. 

PMID- 24590786
TI  - Detecting alternative polyadenylation from microarray data.
AB  - Gene regulation at the posttranscriptional level is often mediated by trans
      acting factors binding the 3' untranslated region (3' UTR) of messenger RNAs
      (mRNAs). Alternative mRNA isoforms differing only in their 3' UTR can thus be
      differentially regulated, and it has been recently shown that this mechanism is
      indeed used by the cell to alter gene regulation effected by microRNAs and RNA
      binding proteins, especially in highly proliferating contexts. Here we describe a
      computational method to analyze alternative 3' UTR isoforms in gene expression
      profiling datasets obtained with Affymetrix 3' IVT microarrays. The approach we
      describe allows the analysis of 3' UTR isoform usage in thousands of publicly
      available gene expression datasets, including many retrospective studies of
      cancer patients equipped with clinical data.

PMID- 24590787
TI  - Quantitative polyadenylation site mapping with single-molecule direct RNA
      sequencing.
AB  - The known regulatory role of 3' untranslated regions (3'UTRs) and poly(A) tails
      in RNA localization, stability, and translation, and polyadenylation regulation
      defects leading to human diseases such as oculopharyngeal muscular dystrophy,
      thalassemias, thrombophilia, and IPEX syndrome underline the need to fully
      characterize genome-wide polyadenylation states and mechanisms across normal
      physiological and disease states. This chapter outlines the quantitative
      polyadenylation site mapping and analysis strategies developed with the single
      molecule direct RNA sequencing technology.

PMID- 24590788
TI  - RHAPA: a new method to quantify alternative polyadenylation.
AB  - 3' end formation of eukaryotic messenger RNAs (mRNAs) is an essential process
      that influences mRNA stability, turnover, and translation. Polyadenylation is the
      process by which mRNAs are cleaved at specific sites in response to specific RNA
      sequence elements and binding of trans-acting protein factors; these cleaved
      mRNAs subsequently acquire non-templated poly(A) tails at their 3' ends.
      Alternative polyadenylation occurs when multiple poly(A) signals are present in
      the primary mRNA transcript, in either the 3' untranslated region (3'UTR) or
      other sites within the mRNA, resulting in multiple transcript variants of
      different lengths. We demonstrate here a new method, termed RHAPA (RNase H
      alternative polyadenylation assay), that employs conventional RT-PCR with gene
      specific oligonucleotide hybridization and RNase H cleavage to directly measure
      and quantify alternatively polyadenylated transcripts. This method gives an
      absolute quantified expression level of each transcript variant and provides a
      way to examine poly(A) signal selection in different cell types and under
      different conditions. Ultimately, it can be used to further examine
      posttranscriptional regulation of gene expression.

PMID- 24590789
TI  - Multiplex analysis of polyA-linked sequences (MAPS): an RNA-seq strategy to
      profile poly(A+) RNA.
AB  - We summarize 12 experimental methods that have been developed for profiling gene
      expression by focusing on the 3'-end of poly(A+) mRNA, distilling both common and
      unique features. Of this family of methods, we provide detailed protocol for
      MAPS, a method we believe is the simplest and most cost-effective for profiling
      gene expression and quantifying alternative polyadenylation events by oligo-dT
      priming followed by random priming and deep sequencing. This method also enables
      library multiplexing by using a set of bar coding primers during PCR
      amplification. We also provide a general guideline for analysis of the data
      generated by MAPS by using the software package maps3end.

PMID- 24590790
TI  - Global and quantitative profiling of polyadenylated RNAs using PAS-seq.
AB  - mRNA alternative polyadenylation (APA) has been increasingly recognized as a
      widespread and evolutionarily conserved mechanism for eukaryotic gene regulation.
      Here we describe a method called poly(A) site sequencing that can not only map
      RNA polyadenylation sites on a transcriptome level but also provide quantitative
      information on the relative abundance of polyadenylated RNAs. This method has
      been successfully used for both global APA analysis and digital gene expression
      profiling. 

PMID- 24590791
TI  - High-throughput sequencing of RNA isolated by cross-linking and
      immunoprecipitation (HITS-CLIP) to determine sites of binding of CstF-64 on
      nascent RNAs.
AB  - Genome-wide analysis of gene expression has changed the RNA world. Recent
      techniques leading to this revolution have been the use of cross-linking and
      immunoprecipitation (CLIP) combined with high-throughput sequencing (HITS-CLIP)
      to determine sites on nascent mRNAs to which RNA-binding proteins bind. Several
      researchers (including us) have been examining the role of RNA-binding proteins
      in polyadenylation, including the role of the 64,000 Mr component of the cleavage
      stimulation factor, CstF-64. In this chapter, we present our optimizations of the
      CLIP procedure for examination of CstF-64 binding to nascent pre-mRNAs expressed
      in testis. For CstF-64 CLIP, we use a well-characterized monoclonal antibody
      (3A7) that recognizes CstF-64. Rather than optimizing tricky but essential RNA
      fragment cloning schemes, we illustrate the use of the proprietary Illumina
      TruSeq Small RNA Sample Preparation kit for this step. Other techniques such as
      SDS-PAGE and the transfer to the nitrocellulose membrane techniques follow the
      original Illumina protocol (though we point out potential pitfalls). Finally, we
      discuss the options for high-throughput sequencing and some general suggestions
      for bioinformatic analysis of the data.

PMID- 24590792
TI  - Polyadenylation in bacteria and organelles.
AB  - Polyadenylation is a posttranscriptional modification present throughout all the
      kingdoms of life with important roles in regulation of RNA stability,
      translation, and quality control. Functions of polyadenylation in prokaryotic and
      organellar RNA metabolism are still not fully characterized, and poly(A) tails
      appear to play contrasting roles in different systems. Here we present a general
      overview of the polyadenylation process and the factors involved in its
      regulation, with an emphasis on the diverse functions of 3' end modification in
      the control of gene expression in different biological systems. 

PMID- 24590793
TI  - In vivo analysis of polyadenylation in prokaryotes.
AB  - Polyadenylation at the 3' ends of mRNAs, tRNAs, rRNAs, and sRNAs plays important
      roles in RNA metabolism in both prokaryotes and eukaryotes. However, the nature
      of poly(A) tails in prokaryotes is distinct compared to their eukaryotic
      counterparts. Specifically, depending on the organism, eukaryotic poly(A) tails
      average between 50 and >200 nt and can easily be isolated by several techniques
      involving oligo(dT)-dependent cDNA amplification. In contrast, the bulk of the
      poly(A) tails present on prokaryotic transcripts is relatively short (<10 nt) and
      is difficult to characterize using similar techniques. This chapter describes
      methods that can circumvent these problems. For example, we discuss how to
      isolate total RNA and characterize its overall polyadenylation status employing a
      poly(A) sizing assay. Furthermore, we describe a technique involving RNase H
      treatment of total RNA followed by northern analysis in order to distinguish
      length of poly(A) tails on various types of transcripts. Finally, we outline a
      useful procedure to clone the poly(A) tails of specific transcripts using 5'-3'
      end-ligated RNA, which is independent of oligo(dT)-dependent cDNA amplification.
      These approaches are particularly helpful in analyzing transcripts with either
      short or long poly(A) tails both in prokaryotes and eukaryotes.

PMID- 24590794
TI  - Polyadenylation of RNA in E. coli: RNA polymerase-associated (rA)n-synthetic
      activities.
AB  - In Escherichia coli, Poly(A) polymerase (PAP) and polynucleotide phosphorylase
      (PNP) are key enzymes thought to be responsible for polyadenylation of the bulk
      of cellular RNA. In this chapter we describe enzymatic in vitro assays for
      monitoring (rA)n-synthetic activity among fractionated E. coli proteins obtained
      after affinity chromatography on immobilized DNA. The enzymatic activities of PAP
      and PNP can be independently monitored among fractionated proteins due to the
      utilization of different nucleoside substrates (respectively, ATP and ADP) by the
      two enzymes. We describe two different methods for monitoring the synthesis of
      polyadenylate: a method based on utilization of a nucleic acid-specific
      fluorescent dye (RiboGreen((r))) and an alternative method based on utilization
      of P(32)-labeled nucleoside phosphates.

PMID- 24590795
TI  - Analysis of the human mitochondrial transcriptome using directional deep
      sequencing and parallel analysis of RNA ends.
AB  - RNA sequencing using next-generation technologies provides comprehensive coverage
      of transcriptomes at a much greater depth than conventional transcriptomic
      methods. The human mitochondrial genome is relatively small, and sequencing its
      transcriptome provides a valuable method to investigate changes in RNA metabolism
      in great detail. Here we describe two methods that use next-generation
      technologies to investigate mitochondrial RNAs. Directional RNA sequencing
      enables the analyses of RNA abundance from each strand of the mitochondrial DNA.
      Parallel analysis of RNA ends enables the analyses of processing of mitochondrial
      transcripts, their termini, and annotation of any new transcripts. 

PMID- 24590796
TI  - Measurement of mitochondrial RNA stability by metabolic labeling of transcripts
      with 4-thiouridine.
AB  - Determination of RNA stability is one of the basic issues addressed in studies of
      RNA metabolism. In a standard approach used for RNA half-life measurement
      synthesis of RNA is inhibited and then the steady-state level of RNA is
      quantified and used for calculations. Here, we present an optimized protocol for
      mitochondrial RNA stability studies without perturbation of transcription and
      present results produced for the mitochondrial CytB messenger RNA. This method
      was originally described for nuclear transcripts and involves metabolic labeling
      of RNA with 4-thiouridine.

PMID- 24590797
TI  - Deadenylation and its regulation in eukaryotic cells.
AB  - Messenger RNA deadenylation is a process that allows rapid regulation of gene
      expression in response to different cellular conditions. The change of the mRNA
      poly(A) tail length by the activation of deadenylation might regulate gene
      expression by affecting mRNA stability, mRNA transport, or translation
      initiation. Activation of deadenylation processes are highly regulated and
      associated with different cellular conditions such as cancer, development, mRNA
      surveillance, DNA damage response, and cell differentiation. In the last few
      years, new technologies for studying deadenylation have been developed. Here we
      overview concepts related to deadenylation and its regulation in eukaryotic
      cells. We also describe some of the most commonly used protocols to study
      deadenylation in eukaryotic cells. 

PMID- 24590798
TI  - Assaying mRNA deadenylation in vitro.
AB  - Deadenylation is the removal of poly(A) tails from mRNA. This chapter presents
      two methods to assay deadenylation in vitro. The first is a quick and
      quantitative assay for the degradation of radiolabeled poly(A) that can easily be
      adapted to be used for many different enzymes. The second method uses an extract
      from Drosophila embryos to catalyze the deadenylation of an RNA dependent on a
      specific sequence that also directs deadenylation in vivo.

PMID- 24590799
TI  - Assaying mRNA deadenylation in vivo.
AB  - Deadenylation is the removal of poly(A) tails from mRNA. Here, we present two
      methods for assaying deadenylation in vivo. The first is a method for measuring
      bulk poly(A) tail lengths. When combined with a block in transcription, the
      method can be used for measuring the rate of bulk poly(A) tail shortening. The
      second is an RT-PCR method to determine the poly(A) tail lengths of individual
      RNAs. Again in combination with a block of transcription, the method permits the
      rate of deadenylation of an individual RNA to be measured. 

PMID- 24590800
TI  - In vitro analysis of RNA degradation catalyzed by deadenylase enzymes.
AB  - In this chapter, we describe a method for purification and analysis of the
      enzymatic activity of deadenylase enzymes. Nearly all eukaryotic messenger RNAs
      are modified at the 3' end by the addition of an adenosine polymer: the poly
      adenosine tail. The poly(A) tail plays a central role in protein expression and
      mRNA fate. The poly(A) tail promotes translation of the mRNA. Shortening of the
      poly(A) tail, referred to as deadenylation, reduces protein synthesis and
      initiates destruction of the mRNA. A specialized class of exoribonucleases,
      called deadenylase enzymes, carries out this process. Deadenylases are found
      throughout eukarya, but their functions remain largely unexplored. We present a
      detailed protocol to analyze deadenylase activity in vitro. First, recombinant
      deadenylase enzyme is over-expressed and purified from bacteria. Next, labeled
      RNA substrate is prepared. Deadenylation reactions are performed, and reaction
      products are analyzed by denaturing gel electrophoresis. Reaction rates are then
      determined quantitatively. Crucial controls and experimental parameters are
      described along with practical tips that promote success.

PMID- 24590801
TI  - MicroRNA-mediated deadenylation in a mammalian cell-free system.
AB  - MicroRNAs (miRNAs) are 21-22 nucleotide small noncoding RNAs that regulate gene
      expression posttranscriptionally. The miRNA is incorporated into the miRNP
      effector complex. The miRNP complex binds to the mRNA containing the target
      sites, which are partially homologous to the miRNA sequence, and represses
      protein synthesis. One of the critical functions of miRNP is the recruitment of
      deadenylase complexes to the target mRNAs. Deadenylation causes translational
      inhibition as well as mRNA destabilization. In this chapter, we describe our
      method to recapitulate miRNA-mediated deadenylation in a mammalian cell-free
      system.

PMID- 24590802
TI  - Quantitative analysis of deadenylation-independent mRNA decay by a modified
      MBRACE assay.
AB  - Endonuclease cleavage is the rate-limiting step in the decay of nonsense
      containing human beta-globin mRNA in erythroid cells. The 5'-truncated
      intermediates thus generated are polyadenylated and more stable than the parent
      mRNA. Northern blotting is commonly used to measure the decay rate of full-length
      mRNA, and S1 nuclease protection is used to assay the fate of decay
      intermediates. We have adapted the more sensitive and facile MBRACE assay (Lasham
      et al., Nucleic Acids Res 38: e19, 2010) to quantitatively monitor the decay
      process by detecting full-length beta-globin and its decay intermediates.

PMID- 24590803
TI  - Essential medicines for COPD and asthma in low and middle-income countries.
AB  - Access to medications for chronic disease management is limited in many low and
      middle-income countries (LMICs), resulting in suboptimal care and avoidable
      morbidity and mortality. We performed a survey of COPD and asthma medicines that
      appeared on the national essential medicines lists (NEMLs) of 32 LMICs. Nearly
      all countries (>90%) had assigned essential medicines for treatment of
      exacerbations and early stable disease stages, but not for steps 4 (22%) and 5
      (6%) controlled asthma management. The number of treatment options was limited,
      with long-acting beta2-agonists (LABA) and combination dosage forms being notably
      absent. Suboptimal availability of chronic respiratory disease medicines suggests
      that implementation of NEMLs is the main problem in clinical practice. 

PMID- 24590805
TI  - Sn(IV) porphyrin scaffolds for axially bonded multiporphyrin arrays: synthesis
      and structure elucidation by NMR studies.
AB  - A simple, one-step, supramolecular strategy was adopted to synthesize Sn(IV) 
      porphyrin-based axially bonded triads and higher oligomers by using meso-pyridyl
      Sn(IV) porphyrin, meso-hydroxyphenyl-21,23-dithiaporphyrin, and Ru(II) porphyrin
      as building blocks and employing complementary and non-interfering Sn(IV) ?O and
      Ru(II) ???N interactions. The multiporphyrin arrays are stable and robust and
      were purified by column chromatography. (1) H, (1) H-(1) H COSY and NOESY NMR
      spectroscopic studies were used to unequivocally deduce the molecular structures
      of Sn(IV) -porphyrin-based triads and higher oligomers. Absorption and
      electrochemical studies indicated weak interaction among the different porphyrin
      units in triads and higher oligomers, in support of the supramolecular nature of
      the arrays. Steady-state fluorescence studies on triads indicated the possibility
      of energy transfer in the singlet state from the basal Sn(IV) porphyrin to the
      axial 21,23-dithiaporphyrin. However, the higher oligomers were weakly
      fluorescent due to the presence of heavy Ru(II) porphyrin unit(s), which quench
      the fluorescence of the Sn(IV) porphyrin and 21,23-dithiaporphyrin units. 

PMID- 24590804
TI  - Dogs learn to solve the support problem based on perceptual cues.
AB  - Numerous recent studies have investigated how animals solve means-end tasks and
      unraveled considerable variation in strategies used by different species.
      Domestic dogs (Canis familiaris) have typically performed comparably poorly in
      physical cognition tasks, but a recent study showed that they can solve the on
      off condition of the support problem, where they are confronted with two boards,
      one with a reward placed on it and the other with a reward placed next to it. To
      explore which strategies dogs use to solve this task, we first tested 37 dogs
      with the on-off condition tested previously and then tested subjects that passed
      this condition with three transfer tasks. For the contact condition, the
      inaccessible reward was touching the second board. For the perceptual containment
      condition, the inaccessible reward was surrounded on three sides by the second
      board, but not supported by it, whereas for the gap condition, discontinuous
      boards were used. Unlike in the previous study, our subjects did not perform
      above chance level in the initial trials of the on-off condition, but 13 subjects
      learned to solve it. Their performance in the transfer tasks suggests that dogs
      can learn to solve the support problem based on perceptual cues, that they can
      quickly adopt new cues when old ones become unreliable, but also that some
      apparently inherent preferences are hard to overcome. Our study contributes to
      accumulating evidence demonstrating that animals typically rely on a variety of
      perceptual cues to solve physical cognition tasks, without developing an
      understanding of the underlying causal structure. 

PMID- 24590808
TI  - Induction of immunoregulatory CD271+ cells by metastatic tumor cells that express
      human endogenous retrovirus H.
AB  - Human endogenous retroviruses (HERV) are associated with many diseases such as
      autoimmune diseases and cancer. Although the frequent expression of a variety of
      HERVs in tumor cells has been demonstrated, their functional contributions in
      cancer are as yet unclear. Intriguingly, HERVs and other retroviruses include an
      immunosuppressive domain in their transmembrane envelope proteins, but its
      mechanism of action and cancer relevance are obscure. In this study, we
      demonstrate that the human endogenous retrovirus HERV-H has a critical role in
      tumor metastasis and immune escape. We found that expression of herv-h mRNA was
      elevated in metastatic tumor cells undergoing epithelial-to-mesenchymal
      transition (EMT) and in primary tumor tissues from advanced colon cancer. The
      immunosuppressive peptide H17 derived from HERV-H was sufficient to induce EMT in
      tumor cells that expressed low levels of HERV-H, and it amplified this event
      within the tumor microenvironment. H17 also stimulated CCL19 expression in tumor
      cells, which in turn recruited and expanded a population of pluripotent
      immunoregulatory CD271(+) cells, which included mesenchymal stem cells and
      myeloid-derived suppressor cells. In tumor tissues from patients with advanced
      colon cancer, we confirmed that CD271(+) cells were increased in HERV
      H(+)CCL19(+) tumor tissues. Notably, RNAi-mediated change of HERV-H or CCL19, or
      depletion of CD271(+) cells, improved immune responses in vitro and in vivo
      accompanied by tumor regression. Together, our results argued that HERV-H is a
      critical determinant of immune escape in cancer, suggesting its candidacy as a
      promising therapeutic target to treat patients with advanced cancer.

PMID- 24590807
TI  - A novel radiotracer to image glycogen metabolism in tumors by positron emission
      tomography.
AB  - The high rate of glucose uptake to fuel the bioenergetic and anabolic demands of
      proliferating cancer cells is well recognized and is exploited with (18)F-2
      fluoro-2-deoxy-d-glucose positron emission tomography ((18)F-FDG-PET) to image
      tumors clinically. In contrast, enhanced glucose storage as glycogen
      (glycogenesis) in cancer is less well understood and the availability of a
      noninvasive method to image glycogen in vivo could provide important biologic
      insights. Here, we demonstrate that (18)F-N-(methyl-(2-fluoroethyl)-1H
      [1,2,3]triazole-4-yl)glucosamine ((18)F-NFTG) annotates glycogenesis in cancer
      cells and tumors in vivo, measured by PET. Specificity of glycogen labeling was
      demonstrated by isolating (18)F-NFTG-associated glycogen and with stable
      knockdown of glycogen synthase 1, which inhibited (18)F-NFTG uptake, whereas
      oncogene (Rab25) activation-associated glycogen synthesis led to increased
      uptake. We further show that the rate of glycogenesis is cell-cycle regulated,
      enhanced during the nonproliferative state of cancer cells. We demonstrate that
      glycogen levels, (18)F-NFTG, but not (18)F-FDG uptake, increase proportionally
      with cell density and G1-G0 arrest, with potential application in the assessment
      of activation of oncogenic pathways related to glycogenesis and the detection of
      posttreatment tumor quiescence.

PMID- 24590814
TI  - Number of tumor foci as predictor of lateral lymph node metastasis in papillary
      thyroid carcinoma.
AB  - BACKGROUND: The purpose of this study was to determine the clinicopathologic
      characteristics of patients with papillary thyroid carcinoma (PTC) by the number
      of tumor foci. METHODS: A retrospective analysis of 2095 patients with PTC was
      performed. The study population was divided into 4 groups based on the number of
      tumor foci: N1 (1 tumor focus), N2 (2 foci), N3 (3 foci), and N4 (4 or more
      foci). RESULTS: An increasing number of tumor foci was significantly associated
      with older age at diagnosis (p = .006), cervical lymph node metastasis (p <
      .001), and advanced TNM stage of disease (p = .001) at initial surgery. The
      multivariate adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs)
      for the N2, N3, and N4 groups compared to the N1 group for lateral lymph node
      metastasis were OR 1.53 (95% CI, 1.05-2.22), OR 2.57 (95% CI, 1.50-4.42), and OR
      2.88 (95% CI, 1.42-5.84), respectively. CONCLUSION: An increase in the number of
      tumor foci was strongly associated with older age at diagnosis, cervical lymph
      node metastasis, and advanced TNM stage of PTC. The number of tumor foci
      independently predicted lateral lymph node metastasis.

PMID- 24590809
TI  - LIMD2 is a small LIM-only protein overexpressed in metastatic lesions that
      regulates cell motility and tumor progression by directly binding to and
      activating the integrin-linked kinase.
AB  - Proteins that communicate signals from the cytoskeleton to the nucleus are prime
      targets for effectors of metastasis as they often transduce signals regulating
      adhesion, motility, and invasiveness. LIM domain proteins shuttle between the
      cytoplasm and the nucleus, and bind to partners in both compartments, often
      coupling changes in gene expression to extracellular cues. In this work, we
      characterize LIMD2, a mechanistically undefined LIM-only protein originally found
      to be overexpressed in metastatic lesions but absent in the matched primary
      tumor. LIMD2 levels in fresh and archival tumors positively correlate with cell
      motility, metastatic potential, and grade, including bladder, melanoma, breast,
      and thyroid tumors. LIMD2 directly contributes to these cellular phenotypes as
      shown by overexpression, knockdown, and reconstitution experiments in cell
      culture models. The solution structure of LIMD2 that was determined using nuclear
      magnetic resonance revealed a classic LIM-domain structure that was highly
      related to LIM1 of PINCH1, a core component of the integrin-linked kinase-parvin
      pinch complex. Structural and biochemical analyses revealed that LIMD2 bound
      directly to the kinase domain of integrin-linked kinase (ILK) near the active
      site and strongly activated ILK kinase activity. Cells that were null for ILK
      failed to respond to the induction of invasion by LIMD2. This strongly suggests
      that LIMD2 potentiates its biologic effects through direct interactions with ILK,
      a signal transduction pathway firmly linked to cell motility and invasion. In
      summary, LIMD2 is a new component of the signal transduction cascade that links
      integrin-mediated signaling to cell motility/metastatic behavior and may be a
      promising target for controlling tumor spread.

PMID- 24590815
TI  - Objective validation of central sensitization in the rat UVB and heat rekindling
      model.
AB  - BACKGROUND: The UVB and heat rekindling (UVB/HR) model shows potential as a
      translatable inflammatory pain model. However, the occurrence of central
      sensitization in this model, a fundamental mechanism underlying chronic pain, has
      been debated. Face, construct and predictive validity are key requisites of
      animal models; electromyogram (EMG) recordings were utilized to objectively
      demonstrate validity of the rat UVB/HR model. METHODS: The UVB/HR model was
      induced on the heel of the hind paw under anaesthesia. Mechanical withdrawal
      thresholds (MWTs) were obtained from biceps femoris EMG responses to a gradually
      increasing pinch at the mid hind paw region under alfaxalone anaesthesia, 96 h
      after UVB irradiation. MWT was compared between UVB/HR and SHAM-treated rats
      (anaesthetic only). Underlying central mechanisms in the model were
      pharmacologically validated by MWT measurement following intrathecal N-methyl-d
      aspartate (NMDA) receptor antagonist, MK-801, or saline. RESULTS: Secondary
      hyperalgesia was confirmed by a significantly lower pre-drug MWT {mean [+/
      standard error of the mean (SEM)]} in UVB/HR [56.3 (+/-2.1) g/mm(2) , n = 15]
      compared with SHAM-treated rats [69.3 (+/-2.9) g/mm(2) , n = 8], confirming face
      validity of the model. Predictive validity was demonstrated by the attenuation of
      secondary hyperalgesia by MK-801, where mean (+/-SEM) MWT was significantly
      higher [77.2 (+/-5.9) g/mm(2) n = 7] in comparison with pre-drug [57.8 (+/-3.5)
      g/mm(2) n = 7] and saline [57.0 (+/-3.2) g/mm(2) n = 8] at peak drug effect. The
      occurrence of central sensitization confirmed construct validity of the UVB/HR
      model. CONCLUSIONS: This study used objective outcome measures of secondary
      hyperalgesia to validate the rat UVB/HR model as a translational model of
      inflammatory pain.

PMID- 24590816
TI  - A Bayesian approach to dose-finding studies for cancer therapies: incorporating
      later cycles of therapy.
AB  - We consider phase I dose-finding studies for cytotoxic drugs in cancer, where the
      objective is identification of a target dose (TD100delta ) associated with the
      probability delta of a dose-limiting toxicity (DLT). Previous authors have
      presented a design utilising a Bayesian decision procedure based on a logistic
      regression model to describe the relationship between dose and the risk of a DLT
      (LRDP). A cautious prior, chosen to ensure that the first cohort of patients are
      given the lowest dose, is combined with binary observations of DLTs to update
      model parameters and choose a safe dose for the next cohort. This process
      continues with each new cohort of patients. Typically, only DLTs occurring in the
      first treatment cycle are included. To incorporate data from later cycles, a new
      Bayesian decision procedure based on an interval-censored survival model (ICSDP)
      has been developed. This models the probability that the first DLT occurs in each
      specific cycle via the probability of a DLT during a specific cycle, conditional
      on having no DLT in any previous cycle. The second cohort of patients start after
      responses have been obtained from the first cycle of the first cohort, and
      subsequently, dose selection for each new cohort is based on DLTs observed across
      all completed cycles for all patients. A simulation study comparing the ICSDP and
      LRDP showed that the ICSDP induces faster updating of the current estimate of the
      target dose, leading to shorter trials and fewer patients, whilst keeping the
      same level of accuracy.

PMID- 24590818
TI  - Rhodium enalcarbenoids: direct synthesis of indoles by rhodium(II)-catalyzed
      [4+2] benzannulation of pyrroles.
AB  - Disclosed herein is the design of an unprecedented electrophilic rhodium
      enalcarbenoid which results from rhodium(II)-catalyzed decomposition of a new
      class of enaldiazo compounds. The synthetic utility of these enalcarbenoids has
      been successfully demonstrated in the first transition-metal-catalyzed [4+2]
      benzannulation of pyrroles, thus leading to substituted indoles. The new
      benzannulation has been applied to the efficient synthesis of the natural product
      leiocarpone as well as a potent adipocyte fatty-acid binding protein inhibitor. 

PMID- 24590817
TI  - Merging gold and organocatalysis: a facile asymmetric synthesis of annulated
      pyrroles.
AB  - The combination of cinchona-alkaloid-derived primary amine and Au(I) -phosphine
      catalysts allowed the selective C-H functionalization of two adjacent carbon
      atoms of pyrroles under mild reaction conditions. This sequential dual activation
      provides seven-membered-ring-annulated pyrrole derivatives in excellent yields
      and enantioselectivities.

PMID- 24590819
TI  - Communicating the parameter uncertainty in the IQWiG efficiency frontier to
      decision-makers.
AB  - The Institute for Quality and Efficiency in Health Care (IQWiG) developed-in a
      consultation process with an international expert panel-the efficiency frontier
      (EF) approach to satisfy a range of legal requirements for economic evaluation in
      Germany's statutory health insurance system. The EF approach is distinctly
      different from other health economic approaches. Here, we evaluate established
      tools for assessing and communicating parameter uncertainty in terms of their
      applicability to the EF approach. Among these are tools that perform the
      following: (i) graphically display overall uncertainty within the IQWiG EF
      (scatter plots, confidence bands, and contour plots) and (ii) communicate the
      uncertainty around the reimbursable price. We found that, within the EF approach,
      most established plots were not always easy to interpret. Hence, we propose the
      use of price reimbursement acceptability curves-a modification of the well-known
      cost-effectiveness acceptability curves. Furthermore, it emerges that the net
      monetary benefit allows an intuitive interpretation of parameter uncertainty
      within the EF approach. This research closes a gap for handling uncertainty in
      the economic evaluation approach of the IQWiG methods when using the EF. However,
      the precise consequences of uncertainty when determining prices are yet to be
      defined.

PMID- 24590820
TI  - Sir Patrick Dun and the Complete School of Physic in eighteenth-century Dublin.
AB  - INTRODUCTION: 2013 is the tercentenary of the death of Sir Patrick Dun. When Dun
      died in 1713, he left the proceeds of his estate to enhance medical education in
      Dublin by funding chairs in medicine. He showed remarkable innovation, but it
      took 95 years, five Acts of Parliament, two House of Commons enquiries and a
      House of Lords enquiry before Dun's wishes were brought to fruition and
      systematic clinical education was available for Dublin medical students. The
      passage of the final School of Physic Act in 1800 insured that a hospital would
      open in his name and regular clinical education was provided. The physician,
      Richard Steevens, who died 3 years earlier in 1710, left the proceeds of his
      estate to found a hospital, which opened, in his name, in 1733. MATERIALS AND
      METHODS: The contemporary primary sources have been analysed and material from
      relevant secondary sources has been included where appropriate. CONCLUSION:
      Dublin was the beneficiary of these bequests and if circumstances had been more
      favourable, and the proceeds had been used more efficiently at the start of the
      eighteenth-century, Dublin could well have rivalled Edinburgh as the seat of
      medical education in the eighteenth century. In the early nineteenth century, it
      would fulfil that role and equal Edinburgh as one of the primary centres of
      medical education in Europe.

PMID- 24590821
TI  - Pregnancy outcome in chronic myeloid leukemia patients on imatinib therapy.
AB  - INTRODUCTION: Imatinib is a first-line therapy to treat chronic myeloid leukemia
      (CML) patients. MATERIALS AND METHODS: We selected 22 CML cases of pregnancies
      and reported 9 accidental and 13 planned pregnancies that were on imatinib
      therapy. Willing female patients remaining in complete hematological, cytogenetic
      and major molecular responses for at least 2 years planned for pregnancy and were
      advised to stop imatinib for 1 month prior to conception and 3 months after
      conception (first trimester). Willing male patients stopped therapy 1 month prior
      to conception of their wives. In unplanned cases, all patients were in exposure
      to imatinib during conception. Twenty-two pregnancies resulted in seven male
      children and eight female children. There were three spontaneous abortions and
      four elective abortions along with one case of hypospadia and another one of mild
      hydrocephalus. CONCLUSION: We may suggest that planned pregnancy during therapy
      may be encouraged but imatinib therapy in unplanned pregnancy can cause
      spontaneous abortion or congenital anomaly.

PMID- 24590822
TI  - A time-dependent DFT study of the absorption and fluorescence properties of
      graphene quantum dots.
AB  - Absorption and fluorescence spectra of graphene quantum dots (GQDs) have been
      computed by using time-dependent density functional theory (TDDFT). Different
      functionals, including PBE, TPSSh, B3LYP, PBE0, CAM-B3LYP, and LC-omegaPBE, have
      been tested and B3LYP/6-31G(d) has been proven to be the most accurate method for
      our work. The bulk solvent effects of toluene and dichloromethane have been
      assessed by using the polarizable continuum model (PCM). The absorption
      wavelength of GQDs in solvents is red-shifted compared with that in the gas
      phase. Edge functionalization effects analysis shows that a small number of
      substituted groups on GQDs induce a small redshift whereas a large redshift
      occurs when the edges of GQDs are all decorated. Little difference in the
      fluorescent emission was observed in solvents and in the gas phase. Molecular
      orbital transition and transition density matrix analysis have been performed.
      The electronic transition mainly occurs in the middle part of the structure of
      C132. The strong absorption of C132 corresponds to a S0 ->S3 transition and the
      fluorescence emission is ascribed to a S1 ->S0 transition, which indicates that
      Kasha's rule is obeyed. 

PMID- 24590823
TI  - Inhibitory effects of capsaicin on voltage-gated potassium channels by TRPV1
      independent pathway.
AB  - Previously we observed that capsaicin, a transient receptor potential vanilloid 1
      (TRPV1) receptor activator, inhibited transient potassium current (IA) in
      capsaicin-sensitive and capsaicin-insensitive trigeminal ganglion (TG) neurons
      from rats. It suggested that the inhibitory effects of capsaicin on IA have two
      different mechanisms: TRPV1-dependent and TRPV1-independent pathways. The main
      purpose of this study is to further investigate the TRPV1-independent effects of
      capsaicin on voltage-gated potassium channels (VGPCs). Whole cell patch-clamp
      technique was used to record IA and sustained potassium current (IK) in cultured
      TG neurons from trpv1 knockout (TRPV1(-/-)) mice. We found that capsaicin
      reversibly inhibited IA and IK in a dose-dependent manner. Capsaicin (30 MUM) did
      not alter the activation curve of IA and IK but shifted the inactivation-voltage
      curve to hyperpolarizing direction, thereby increasing the number of inactivated
      VGPCs at the resting potential. Administrations of high concentrations capsaicin,
      no use-dependent block, and delay of recovery time course were found on IK and
      IA. Moreover, forskolin, an adenylate cyclase agonist, selectively decreased the
      inhibitory effects of IK by capsaicin, whereas none influenced the inhibitions of
      IA. These results suggest that capsaicin inhibits the VGPCs through TRPV1
      independent and PKA-dependent mechanisms, which may contribute to the capsaicin
      induced nociception.

PMID- 24590825
TI  - Stress and psychological resiliency.
AB  - Over the past decade, there has been an enormous increase in research and
      scientific publications targeting psychological resiliency. However, compared to
      the research on the neurobiology of stress, resiliency research is in its
      relative infancy. Much of the resiliency research has focused on theoretical
      models and the conceptualization of psychological resiliency. Resiliency research
      has been limited by (1) the broad use of the term resiliency; (2) the lack of
      standardized definitions of resiliency; (3) a primary focus on descriptive,
      assessment, and measurement studies; (4) relatively few randomized controlled
      trials to evaluate the efficacy of resiliency enhancement programs; and (5)
      methodological challenges inherent in conducting applied resiliency research.
      Although many recent programs have been initiated in attempts to enhance
      psychological resiliency in targeted populations, such as military personnel,
      relatively few randomized controlled trials have been conducted. Translational
      research, prospective longitudinal cohort studies, and clinical intervention
      trials are needed to better understand the behavioral neurobiology of stress and
      psychological resiliency. 

PMID- 24590826
TI  - Physiological Correlates of Premenstrual Dysphoric Disorder (PMDD).
AB  - Premenstrual dysphoric disorder (PMDD) is a mood disorder with onset of
      functionally impairing or distressing mood symptoms in the late luteal phase of
      the menstrual cycle. Psychophysiologic findings in PMDD broadly fall into two
      categories: vulnerability trait findings, thus categorized because they are
      present in the asymptomatic phases of the menstrual cycle, and state findings,
      which are only present in the symptomatic late luteal phase and which are
      potentially representative of the hormonal events and biological mechanisms that
      lead to PMDD. Trait vulnerability markers in PMDD include diminished
      cardiovascular stress responses, lower heart rate variability (reflecting
      increased vagal tone), and lower P300 amplitude, eventually suggesting that women
      with PMDD share a number of physiological correlates with related anxiety and
      mood disorders. State findings in PMDD include lower luteal phase prepulse
      inhibition and altered luteal phase emotion processing. Lower prepulse inhibition
      in the late luteal phase may be an important ovarian steroid-influenced
      indicative of altered serotonergic neurotransmission, of relevance for women with
      PMDD. Attempts to determine the neural correlates of emotion processing in the
      late luteal phase are thus far inconsistent, but promising. 

PMID- 24590824
TI  - Mechanisms and pharmacology of neuropathic pain in multiple sclerosis.
AB  - The neuropathic pain of multiple sclerosis is quite prevalent and severely
      impacts quality of life. A few randomized, placebo-controlled, blinded clinical
      trials suggest that cannabis- and anticonvulsant-based treatments provide partial
      pain relief, but at the expense of adverse events. An even smaller, but emerging,
      number of translational studies are using rodent models of experimental
      autoimmune encephalomyelitis (EAE), which exhibit pain-like behaviors resembling
      those of Multiple sclerosis (MS) patients. These studies not only support the
      possible effectiveness of anticonvulsants, but also compel further clinical
      trials with serotonin-norepinephrine reuptake inhibitors, the immunosuppressant
      drug rapamycin, or drugs which interfere with glutamatergic neurotransmission.
      Future behavioral studies in EAE models are essential toward a new
      pharmacotherapy of multiple sclerosis pain. 

PMID- 24590828
TI  - Associations of coping strategies with diary based pain variables among Caucasian
      and African American patients with osteoarthritis.
AB  - PURPOSE: The purposes of this study are to examine the associations between pain
      coping strategies and daily diary-based pain measures and to determine whether
      these associations differed by race (African American and Caucasian). METHODS:
      Primary care patients from the Durham Veterans Affairs and Duke University
      Medical Centers (N = 153) with hand, hip, or knee osteoarthritis (OA) completed
      electronic pain diaries on a one-weekend day and one weekday. The maximum, range
      (maximum minus minimum pain), and area under the curve (AUC) of joint pain
      ratings were calculated. Pain coping (Coping Strategies Questionnaire (CSQ)
      coping attempts, catastrophizing, and praying/hoping subscale scores) was
      assessed prior to diary entries and at the end of each diary day (total, problem
      focused, and emotion-focused scores from Stone and Neale's Daily Coping
      Inventory). Pearson correlations between pain variables and coping measures were
      examined. Linear mixed models were fit including age, race, weekend/weekday,
      study enrollment site, education level, pain medication use, self-rated health,
      Arthritis Impact Measurement Scales affect and function subscales, and
      interactions of coping measures with race and weekend day/weekday status.
      RESULTS: Correlations between coping and pain measures were 0.12-0.45. In
      adjusted models, maximum pain and pain range were associated with all three diary
      based coping measures; maximum pain was associated with CSQ coping attempts; and
      AUC was associated with CSQ praying/hoping. Interactions were not significant.
      CONCLUSIONS: Among participants with OA, pain coping strategies were related to
      important aspects of the pain experience, particularly pain range and maximum
      pain. However, race did not modify associations of pain coping strategy use and
      the pain experience.

PMID- 24590827
TI  - TP53 and p53 statuses and their clinical impact in diffuse low grade gliomas.
AB  - TP53 is a pivotal gene frequently mutated in diffuse gliomas and particularly in
      astrocytic tumors. The majority of studies dedicated to TP53 in gliomas were
      focused on mutational hotspots located in exons 5-8. Recent studies have
      suggested that TP53 is also mutated outside the classic mutational hotspots
      reported in gliomas. Therefore, we have sequenced all TP53 coding exons in a
      retrospective series of 61 low grade gliomas (LGG) using high throughput
      sequencing technology. In addition, TP53 mutational status was correlated with:
      (i) p53 expression, (ii) tumor type, (iii) chromosome arms 1p/19q status and (iv)
      clinical features of patients. The cohort included 32 oligodendrogliomas (O), 21
      oligoastrocytomas (M) and 8 astrocytomas (A). TP53 mutation was detected in 52.4%
      (32/61) of tumors (34% of O, 71.4% of M and 75% of A). All mutations (38
      mutations in 32 samples) were detected in exons 4, 5, 6, 7, 8 and 10. Missense
      and non-missense mutations, including seven novel mutations, were detected in
      42.6 and 9.8% of tumors respectively. TP53 mutations were almost mutually
      exclusive with 1p/19q co-deletion and were associated with: (i) astrocytic
      phenotype, (ii) younger age, (iii) p53 expression. Using a threshold of 10% p53
      positive tumor cells, p53 expression is an interesting surrogate marker for
      missense TP53 mutations (Se = 92%; Sp = 79.4%) but not for non-missense mutation
      (18.4% of mutations). TP53 and p53 statuses were not prognostic in LGG. In
      conclusion, we have identified novel TP53 mutations in LGG. TP53 mutations
      outside exons 4-8 are rare. Although it remains imperfect, p53 expression with a
      threshold of 10% is a good surrogate marker for missense TP53 mutations and
      appears helpful in the setting of LGG phenotype diagnosis.

PMID- 24590829
TI  - Job stress and agentic-communal personality traits related to serum cortisol
      levels of male workers in a Japanese medium-sized company: a cross-sectional
      study.
AB  - BACKGROUND: Although serum cortisol is a widely accepted index of stress levels,
      associations between job stress and cortisol levels have been inconsistent.
      Individual differences in personality traits were discussed as one compelling
      explanation for this discrepancy. Agentic-communal personality traits have been
      examined as possible predictive factors for psychological stress. PURPOSE: This
      study investigated correlations among agentic-communal personality traits and
      serum cortisol levels. It was also investigated whether job stress levels
      modified correlations between agentic-communal personality and cortisol levels.
      METHODS: Participants were 198 male workers (mean age = 52.2 years) employed by a
      shipbuilding company in Japan. Questionnaire data and blood samples were
      collected during an annual health checkup. Participants completed a self-report
      questionnaire that included the Job Content Questionnaire (JCQ) that assesses job
      control as job stress levels the Communion-Agency scale (CAS) and questions
      regarding health behaviors. RESULTS: Communion positively correlated with serum
      cortisol levels and unmitigated agency negatively correlated with serum cortisol
      levels. Stratified by job control, communion positively correlated with serum
      cortisol levels and agency negatively correlated with serum cortisol levels in
      participants with low levels of job control. Unmitigated agency negatively
      correlated with serum cortisol levels in participants with high levels of job
      control. CONCLUSION: Levels of job control may modify correlations of gender
      related personality with serum cortisol levels. Especially with exposure to high
      job stress, male workers with high femininity (i.e., high communion and low
      agency) were more likely to have a high stress response as measured by serum
      cortisol levels.

PMID- 24590835
TI  - Formation of Ni(x)Co(3-x)S4 hollow nanoprisms with enhanced pseudocapacitive
      properties.
AB  - Hollow nanostructures are of great interest for a wide variety of applications.
      Despite the great advances, synthesis of anisotropic hollow structures is still
      very challenging. In this work, we have developed a simple sacrificial template
      method to synthesize uniform Ni(x)Co(3-x)S4 hollow nanoprisms with tunable
      composition. Tetragonal nanoprisms of nickel-cobalt acetate hydroxide precursors
      with controllable Ni/Co molar ratios are first synthesized and used as the
      sacrificial templates. After a sulfidation process with thioacetamide (TAA) in
      ethanol, the solid precursor prisms can be transformed into the corresponding
      Ni(x)Co(3-x)S4 hollow nanoprisms with a well-defined hollow interior. The
      intriguing structural and compositional features are beneficial for
      electrochemical applications. Impressively, the resultant Ni(x)Co(3-x)S4 hollow
      prisms manifest a high specific capacitance with enhanced cycling stability,
      making them potential electrode materials for supercapacitors.

PMID- 24590836
TI  - Abstracts of the British Psychosocial Oncology Society, 2014 Annual Conference,
      27 - 28 February 2014, Preston, UK.

PMID- 24590837
TI  - Abstracts of the 5th Annual Scientific Meeting of the British Obesity & Metabolic
      Surgery Society, 23-24 January 2014, Leamington Spa, UK.

PMID- 24590838
TI  - Rotating-platform TKA no different from fixed-bearing TKA regarding survivorship
      or performance: a meta-analysis.
AB  - BACKGROUND: Mobile bearings have been compared with fixed bearings used in TKA.
      However, rotating platforms, a specific type of mobile bearing, have not been
      compared with fixed-bearings using meta-analysis. QUESTIONS/PURPOSES: We asked
      whether the performance of a rotating-platform bearing is superior to, comparable
      to, or worse than a fixed bearing. Four areas were investigated: clinical
      performance, component alignment, adverse event rates, and revision rates.
      METHODS: Searches of Medline, EMBASE, Google Scholar, and the Cochrane databases,
      combined with reference lists from published meta-analyses and systematic reviews
      of mobile-bearing versus fixed-bearing prostheses used in TKAs, provided 17
      nonlanguage-restricted studies consisting of 1910 TKAs (966 rotating platform
      versus 944 fixed bearing). Random-effect modeling was used for all meta-analyses,
      thereby mitigating possible effects of heterogeneity among studies. All meta
      analyses were examined for publication bias using funnel plots; publication bias
      was not detected for any meta-analysis. RESULTS: There were no statistically or
      clinically significant differences in clinical performance (clinical scores, ROM,
      and radiographic evaluation), component alignment, revision rates, or adverse
      event rates except for tibial component alignment in the AP plane, which favored
      TKA with fixed-bearings (p = 0.020; standardized mean difference, 0.229; 95% CI,
      0.035-0.422), but the effect size was small enough that it was not considered
      clinically important. CONCLUSIONS: Based on our findings, which agree
      substantially with those of prior systematic reviews of TKAs with mobile-bearing
      versus fixed-bearing prostheses, there is no compelling case for either rotating
      platform or fixed-bearing implant design in terms of clinical performance,
      component alignment, adverse event frequencies, or survivorship. This dataset,
      which was limited to a maximum 6 years followup, is insufficient to address
      questions related to wear or late revisions. We therefore suggest that implant
      choice should be made on the basis of other factors, perhaps including cost or
      surgeon experience.

PMID- 24590840
TI  - Expression of HIF-1alpha and MDR1/P-glycoprotein in refractory mesial temporal
      lobe epilepsy patients and pharmacoresistant temporal lobe epilepsy rat model
      kindled by coriaria lactone.
AB  - Hypoxia-inducible factor-1alpha (HIF-1alpha) is thought to mediate
      pharmacoresistance in tumor by inducing Pgp overexpression. We aimed to
      investigate the expression of HIF-1alpha and MDR1/P-glycoprotein in refractory
      epilepsy, to explore the correlation of HIF-1alpha with epilepsy multidrug
      resistance. We collected hippocampus and mesial temporal lobe (MTL) cortex of
      refractory mesial temporal lobe epilepsy (mTLE) patients that underwent surgery,
      and established a pharmacoresistant TLE rat model kindled by coriaria lactone. We
      used real-time quantitative PCR (RQ-PCR) and western blot to investigate
      expression of HIF-1alpha and MDR1 in hippocampus and MTL/entorhinal cortex. We
      found that the expression of HIF-1alpha and MDR1, at both mRNA and protein
      levels, were up-regulated in hippocampus and MTL cortex of mTLE patients compared
      with the control cortex (all P < 0.05), and increased in hippocampus and
      entorhinal cortex of kindled rat model versus the control group (all P < 0.05).
      These results demonstrated the overexpression of HIF-1alpha and MDR1/Pgp in
      hippocampus and MTL/entorhinal cortex of mTLE patients and the pharmacoresistant
      TLE rat model. HIF-1alpha may have a regulatory effect on MDR1 expression in
      refractory epilepsy, which is probably consistent with MDR mechanism in tumor.

PMID- 24590839
TI  - Diagnosing periprosthetic joint infection: has the era of the biomarker arrived?
AB  - BACKGROUND: The diagnosis of periprosthetic joint infection (PJI) remains a
      serious clinical challenge. There is a pressing need for improved diagnostic
      testing methods; biomarkers offer one potentially promising approach.
      QUESTIONS/PURPOSES: We evaluated the diagnostic characteristics of 16 promising
      synovial fluid biomarkers for the diagnosis of PJI. METHODS: Synovial fluid was
      collected from 95 patients meeting the inclusion criteria of this prospective
      diagnostic study. All patients were being evaluated for a revision hip or knee
      arthroplasty, including patients with systemic inflammatory disease and those
      already receiving antibiotic treatment. The Musculoskeletal Infection Society
      (MSIS) definition was used to classify 29 PJIs and 66 aseptic joints. Synovial
      fluid samples were tested by immunoassay for 16 biomarkers optimized for use in
      synovial fluid. Sensitivity, specificity, and receiver operating characteristic
      curve analysis were performed to assess for diagnostic performance. RESULTS: Five
      biomarkers, including human alpha-defensin 1-3, neutrophil elastase 2,
      bactericidal/permeability-increasing protein, neutrophil gelatinase-associated
      lipocalin, and lactoferrin, correctly predicted the MSIS classification of all
      patients in this study, with 100% sensitivity and specificity for the diagnosis
      of PJI. An additional eight biomarkers demonstrated excellent diagnostic
      strength, with an area under the curve of greater than 0.9. CONCLUSIONS: Synovial
      fluid biomarkers exhibit a high accuracy in diagnosing PJI, even when including
      patients with systemic inflammatory disease and those receiving antibiotic
      treatment. Considering that these biomarkers match the results of the more
      complex MSIS definition of PJI, we believe that synovial fluid biomarkers can be
      a valuable addition to the methods utilized for the diagnosis of infection. LEVEL
      OF EVIDENCE: Level II, diagnostic study. See Instructions for Authors for a
      complete description of levels of evidence.

PMID- 24590841
TI  - Orthostatic hypotension and cognitive impairment: a dangerous association?
AB  - Many studies have addressed the relation between orthostatic hypotension (OH) and
      cognitive impairment (CI) in the elderly, in mild cognitive impairment, vascular
      and neurodegenerative dementias and movement disorders, such as Parkinson's
      disease. However, results concerning both the increased coexistence of the two
      conditions and their causal relationship remain controversial. According to the
      literature three hypotheses can be formulated on the relation between OH and CI.
      In neurodegenerative disease, OH and CI may result from a common pathological
      process which affects areas involved in both cognition and cardiovascular
      autonomic control. Alternatively, OH may lead to cerebral hypoperfusion which is
      supposed to play a role in the development of CI. Finally, recent data suggest
      that CI should probably be considered more a transient symptom of OH than a
      chronic effect. This study reviews the literature reports on the relationship
      between OH and CI, and emphasises the need for longitudinal studies designed to
      investigate this topic. 

PMID- 24590842
TI  - Baicalein ameliorates cognitive deficits in epilepsy-like tremor rat.
AB  - Baicalein has been shown to possess various pharmacological actions. The current
      work was designed to assess the neuroprotection of baicalein against cognitive
      deficits in epilepsy-like tremor rat (TRM). Epileptic characteristics and memory
      functions were assessed by electroencephalograms recording and Morris water maze
      test, respectively. The changes of oxidative indicators including malondialdehyde
      (MDA), catalase (CAT), Cu/Zn-superoxide dismutase (Cu/Zn-SOD), Mn-SOD,
      glutathione (GSH), glutathione peroxidase (GSH-PX) and 8-isoprostane were
      measured using corresponding commercial kits. Real-time RT-PCR and immunoassay
      were employed to detect activities of various inflammatory mediators such as NF
      kappaB p65, TNF-alpha, IL-1beta, IL-6 and IL-10. Western blot analysis was
      performed to determine heat shock protein (HSP) 70 and mitogen-activated protein
      kinases (MAPKs) (including ERK, JNK and p38) proteins. Our results illustrated
      that baicalein significantly ameliorated epileptiform activity and cognitive
      deficits in TRM. Besides, reduced oxidative stress and inflammatory responses
      were also found in TRM treated with baicalein. Furthermore, there were evident
      alterations of HSP70 and MAPK cascades at protein levels after 14-day
      pretreatment with baicalein. It was concluded that the neuroprotective effect of
      baicalein against cognitive dysfunction might be associated with suppressing
      oxidative stress, inhibiting inflammation and mediating HSP70 as well as MAPK
      cascades in absence-like TRM.

PMID- 24590843
TI  - Multiple sex chromosomes in the light of female meiotic drive in amniote
      vertebrates.
AB  - It is notable that the occurrence of multiple sex chromosomes differs
      significantly between major lineages of amniote vertebrates. In this respect,
      birds are especially conspicuous, as multiple sex chromosomes have not been
      observed in this lineage so far. On the other hand, in mammals, multiple sex
      chromosomes have evolved many times independently. We hypothesize that this
      contrast can be related to the different involvement of sex-specific sex
      chromosomes in female meiosis subjected to the female meiotic drive under male
      versus female heterogamety. Essentially, the male-specific Y chromosome is not
      involved in female meiosis and is therefore sheltered against the effects of the
      female meiotic drive affecting the X chromosome and autosomes. Conversely, the Z
      and W sex chromosomes are both present in female meiosis. Nonrandom segregation
      of these sex chromosomes as a consequence of their rearrangements connected with
      the emergence of multiple sex chromosomes would result in a biased sex ratio,
      which should be penalized by selection. Therefore, the emergence of multiple sex
      chromosomes should be less constrained in the lineages with male rather than
      female heterogamety. Our broader phylogenetic comparison across amniotes supports
      this prediction. We suggest that our results are consistent with the widespread
      occurrence of female meiotic drive in amniotes. 

PMID- 24590844
TI  - [A neuropsychological comparison of bipolar disorder and adult attention deficit
      hyperactivity disorder].
AB  - AIM: The present study aimed to compare cognitive signs of bipolar disorder
      patients with that of adult attention-deficit/hyperactivity disorder (ADHD)
      patients. METHOD: The study comprised 66 bipolar disorder patients, 63 ADHD
      patients, and 58 healthy controls.Structured Clinical Interview for DSM-IV Axis-I
      Disorders (SCID-I), Wender Utah Rating Scale, and Adult Attention
      Deficit/Hyperactivity Rating Scale were performed in all subjects, whereas
      bipolar disorder patients underwent additional Hamilton Depression Rating Scale
      and Young Mania Rating Scale. Subsequently, all participants underwent cognitive
      assessment including Digit Ordering Test, Verbal Memory Process Test, Wisconsin
      Card Sorting Test and Stroop Test. RESULTS: Bipolar disorder, ADHD and control
      groups did not differ significantly from each other with regard to age, sex and
      duration of education. Bipolar patients displayed poorer performance in Digit
      Span Test, Verbal Memory Process Test, Wisconsin Card Sorting Test and Stroop
      Test as compared to the control group. ADHD patients were worse than the control
      subjects in Stroop Test (subtest of difference in times). Bipolar disorder
      patients were poorer than ADHD patients in cognitive tests except for Stroop
      Test. CONCLUSION: In general, bipolar disorder patients have much more severe
      cognitive impairment than ADHD patients in terms of verbal memory and executive
      functions. The results supports the idea of bipolar disorder and ADHD are
      different, at least in terms of cognitive performance.

PMID- 24590845
TI  - [The evaluation of the relationships between marital adjustment, attachment
      styles, temperament and character features].
AB  - OBJECTIVE: The aim of the study was to investigate the relationships between
      marital adjustment and demographics, attachment styles, temperament, and
      character profiles of the couples. METHOD: The study group included 25 couples
      that presented to a psychiatry clinic with marital problems and 25 couples
      without marital problems and those who were not diagnosed with any psychiatric
      disorder as the control group. Structured Clinical Interview for DSM-IV
      Disorders, Structured Clinical Interview for DSM-III-R Axis-II Personality
      Disorders, Temperament and Character Inventory, Birtchnell Marital Partner
      Evaluation Scale, and Experiences in Close Relationships Inventory were used.
      Sociodemographic and some marital characteristics were recorded on a separate
      form. RESULTS: It was found that the men and women in the study group thought of
      each other as less reliable than the controls. Men were more detached and
      controlled by women and women were more dependent on men. Attachment styles of
      women in the study group were avoidant and anxious while men had higher scores in
      the avoidance dimension. In the study group, women received higher scores for
      harm avoidance, sentimentality, congruent second nature and lower scores for
      empathy subscales, while men received lower scores for attachment, self
      forgetfulness, self-transcendence and higher scores for congruent second nature.
      Overall, 48% of the women in the study group were found to have depression.
      DISCUSSION: We found that men and women couples with marital problems were
      different from controls in the way they evaluated each other, and these
      differences were related to temperament, character and attachment patterns.

PMID- 24590846
TI  - [Crime analysis regarding sex offenders in Turkey: psychological profiling,
      cognitive distortions and psychopathy among rapists].
AB  - AIM: In this study the characteristics offenders and victims that contribute to
      offender profiling are analyzed in cases of sexual assault. The analysis of
      sexual assaults are identifies the relationship between these characteristics and
      sex crimes by examining the elements which contribute to sex crimes including
      demographic characteristics, domestic and developmental conditions, forensic
      history, cognitive distortions and psychopathy. METHODS: The Interviewing Tool
      For Sex Crimes, Cognitive Distortions Question Tool About Rape, and Levenson Self
      Report Psychopathy Scale (LSRP) were applied to 106 male convicts between the
      ages of 18-65 or a control group consisting of 100 males volunteers between the
      age range of 18-65 from 11 different closed prisons. RESULTS: The results of the
      cognitive distortions questionnaire score was significantly different among sex
      offenders compared to innocent individuals. The level of cognitive distortion is
      significantly greater among sex offenders. The first and the second psychopathy
      scores are significantly higher than the scores of comparison group, with the
      second testing revealing increased scores in comparison to the first among sex
      offenders. CONCLUSION: The typology of most of sex offenders can be evaluated as
      opportunistic. This study serves as an initial point of reference for the
      necessary theoretical studies of risk assessment, common in the forensic
      psychology field not yet applied in Turkey.

PMID- 24590848
TI  - [Suicidal ideation and completed suicide in The Decameron].
AB  - OBJECTIVE: To extend our understanding of suicidal ideation and completed suicide
      via examination of a medieval Italian text-in particular, examination of the role
      of social and environmental triggers in such events. Previous studies have
      successfully examined the texts of ancient Greco-Roman, Old Norse, and Finnish
      civilizations to better understand the circumstances associated with suicidal
      ideation and completed suicide. Those texts included depictions of suicide by
      people without any apparent mental disorder in response to painful
      social/environmental circumstances. MATERIALS AND METHODS: The Decameron, a
      collection of 100 short stories written by Giovanni Boccaccio in 1349-51, was
      examined in detail. The setting of The Decameron is during the Black Death and
      concerns a group of 10 people that leave plague-ridden Florence for a holiday in
      the countryside. On each of the 10 days of their trip, each individual tells a
      story, which in total form the 100 stories of Boccaccio's work. For the present
      study, all mentions of suicidal ideation and completed suicide were listed and
      arranged with appropriate headings. RESULTS: In total, 9 accounts of suicidal
      ideation and 4 accounts of completed suicide were identified, all of which were
      in response to social stressors, particularly romantic problems. CONCLUSION:
      Suicidal ideation and completed suicide in response to social stressors was a
      feature of The Decameron and it is feasible that this may have been a feature of
      medieval Italian culture. This would be in agreement with the findings of other
      studies that suggest that although commonly occurring in response to mental
      disorder, suicide can occur independently of such disorder as a result of a
      predicament in which an individual finds him/herself.

PMID- 24590847
TI  - [The effect of family-to-family support programs provided for families of
      schizophrenic patients on information about illness, family burden and self
      efficacy].
AB  - OBJECTIVE: This study was conducted to determine the effects of family-to-family
      support programs provided for the families of schizophrenic patients on the need
      for information about the illness, family burden and self-efficacy METHOD: The
      study was carried out with 34 relatives who have key rolesin the lives of 34
      outpatients who were diagnosed with schizophrenia under DSM-IV-TR. A volunteering
      family member was given training about the purpose, contents and planning of the
      program. Thefamily member who had been trainedthen extended this training to
      other family members with the assistance of the psychiatric nurse. The training
      was done once a week, for atotal of 12 sessions. The data were collected using a
      Disease Information Form (DIF), the Perceived Family Burden Scale (PFBS) and the
      Self-Efficacy Scale (SES). RESULTS: There was a significant decrease in the PFBS
      objective scores (from 11.76+/-3.89 to 9.82+/-4.03, p=0.000), subjective scores
      (from 37.85+/-14.57 to 32.74+/-4.39, p=0.030) and total scores (from 49.62+/
      18.25 to 42.56+/-7.56, p=0.005) and a significant increase in the SESS scores
      (from 82.65+/-12.01 to 97.79+/-7.17, p=0.000). Before training, 58.8% of family
      members correctly answered that schizophrenia is a brain disease, while 94.1%
      correctly stated that,it must be treated with medication;however, 55.9% of
      caregivers incorrectly believed in magical attributions relating to the
      disease.After training, all caregivers were able to answer correctly. CONCLUSION:
      A family-to-family support program was found to be effective in reducing
      caregivers' need for information, reducing their burden, and increasing their
      self-efficacy in our country.

PMID- 24590849
TI  - [The validity and reliability study of MBPI (Multidimensional Blood/Injury Phobia
      Inventory)].
AB  - OBJECTIVE: This study aims to translate the 40-item MBPI (Multidimensional
      Blood/Injury Phobia Inventory) into Turkish and examination the reliability and
      validity figures of this scale. METHOD: Trained interviewers assessed 477 factory
      workers using a battery of self-report measures including demographic information
      and MBPI that had been translated into Turkish by the study team. 61 of the 477
      were also interviewed face-to-face by the investigator using the anxiety
      disorders/phobias sections of the CIDI (Composite International Diagnostic
      Interview). RESULTS: MBPI had high internal consistency value (Cronbach alpha=
      0.94). Validity studies showed scales successfully discriminated patient groups
      from healthy controls. Factor analysis of MBPI resulted in five factors; the
      factor contents were very similar to the original scale. CONCLUSION: Our study
      has demonstrated the validity and reliability of the Turkish version of MBPI.

PMID- 24590850
TI  - [Creativity and bipolar disorder].
AB  - The relationship between creativity and bipolar disorder has been an intriguing
      topic since ancient times. Early studies focused on describing characteristics of
      creative people. From the last quarter of the twentieth century, researchers
      began to focus on the relationship between mood disorders and creativity.
      Initially, the studies were based on biographical texts and the obtained results
      indicated a relationship between these two concepts. The limitations of the
      retrospective studies led the researchers to develop systematic investigations
      into this area. The systematic studies that have focused on artistic creativity
      have examined both the prevalence of mood disorders and the creative process. In
      addition, a group of researchers addressed the relationship in terms of affective
      temperaments. Through the end of the 90's, the scope of creativity was widened
      and the notion of everyday creativity was proposed. The emergence of this notion
      led researchers to investigate the associations of the creative process in
      ordinary (non-artist) individuals. In this review, the descriptions of creativity
      and creative process are mentioned. Also, the creative process is addressed with
      regards to bipolar disorder. Then, the relationship between creativity and
      bipolar disorder are evaluated in terms of aforementioned studies (biographical,
      systematic, psychobiographical, affective temperaments). In addition, a new
      model, the "Shared Vulnerability Model" which was developed to explain the
      relationship between creativity and psychopathology is introduced. Finally, the
      methodological limitations and the suggestions for resolving these limitations
      are included.

PMID- 24590851
TI  - [Metallic mercury poisoning and neuropsychological effects: a case report].
AB  - Mercury is an extremely toxic heavy metal that can devastate central nervous
      system. We present the case of a 15 year old adolescent with mercury intoxication
      following 4 days of exposure to elemental mercury at home who was consulted by
      department of pediatrics with complaints of demonstrated emotional lability,
      memory impairment, disinhibition, and impulsivity. Olanzapin 2,5 mg/day was
      initiated. Her neuropsychological performance was evaluated by a
      neuropsychological test battery at initial examination. Deterioration in
      neuropsychological functions like interference effect and attention (Stroop Test
      TBAG form), verbal fluency and switching to other category (Verbal Fluency Test,
      /(VFT), verbal short term and long term memory and recognition (Auditory Verbal
      Learning Test, /(AVLT) was detected. In 9 months follow up period her complaints
      resolved. Initial neuropsychological deficits were also fully recovered at follow
      up. There was an increase in intelligence scores with increased ability to pay
      and sustain attention. She had better performance at Stroop Test TBAG form, VFT
      and AVLT which was similar to her normal peers. In this case report, the clinical
      aspects of central nervous system involvement in mercury intoxication and
      protection from potential toxic effects of laboratory materials like mercury at
      schools were discussed. School administrators should be aware of and parents and
      students should be given necessary protective information.

PMID- 24590852
TI  - [Mania associated with quetiapine treatment].
AB  - Presently, the use of atypical antipsychotics is getting increasingly widespread.
      There are several mania/hypomania cases that have been associated with atypical
      antipsychotic treatment that also display antimanic, antidepressive and
      anxiolytic effects in addition to their antipsychotic effects. In this study, a
      case of schizophrenia in which manic symptoms developed after increasing the
      dosage of quetiapine to 300 mg/day, and subsequently disappeared after cessation
      of treatment is presented. Although the blockage of 5HT2 receptors and the
      disinhibition of frontal dopamine secretion seemed to be the reasons for the
      development of the mania/hypomania related to atypical antipsychotics, the
      mechanism is not clear. During the use of atypical antipsychotics, clinicians
      should be cautious to patients' mood fluctuations.

PMID- 24590853
TI  - [Editorial].

PMID- 24590854
TI  - Immobilized chicks as a model system for early-onset developmental dysplasia of
      the hip.
AB  - We have almost no understanding of how our joints take on their range of
      distinctive shapes, despite the clinical relevance of joint morphogenesis to
      postnatal skeletal malformations such as developmental dysplasia of the hip
      (DDH). In this study, we investigate the role of spontaneous prenatal movements
      in joint morphogenesis using pharmacological immobilization of developing chicks,
      and assess the system as a suitable model for early-onset hip dysplasia. We show
      that, prior to joint cavitation, the lack of dynamic muscle contractions has
      little impact on the shape of the hip joint. However, after the timepoint at
      which cavitation occurs, a dramatic effect on hip joint morphogenesis was
      observed. Effects in the immobilized chicks included flattening of the proximal
      femur, abnormal orientation of the pelvis relative to the femur and abnormal
      placement and coverage of the acetabulum. Although many clinical case studies
      have identified reduced or restricted movement as a risk factor for DDH, this
      study provides the first experimental evidence of the role of prenatal movements
      in early hip joint development. We propose that the immobilized chick embryo
      serves as a suitable model system for the type of early-onset DDH which arises
      due to neuromuscular conditions such as spinal muscular atrophy.

PMID- 24590856
TI  - Characterization and distribution of poly(3-hexylthiophene) phases in an annealed
      blend film.
AB  - The characteristic absorption spectra of three kinds of phases, the isolated,
      ordered, and disordered phases, in a solvent-vapor annealed poly(3
      hexylthiophene)/[6,6]-phenyl-C61 -butyric acid methyl ester (P3HT/PCBM) blend
      film were studied by means of spectroelectrochemistry (SEC) and time-resolved
      absorption spectroscopy (TAS). The results reveal that the content of three
      phases are 12 % isolated, 37 % ordered, and 51 % disordered for the annealed P3HT
      neat film, and 25 % isolated, 31 % ordered, and 44 % disordered for the annealed
      P3HT/PCBM blend film. The vertical distribution of the different phases in the
      blend film was studied by SEC, and the results show that the ordered and isolated
      phases are mainly distributed in the top and in the bottom of the annealed films,
      respectively, while the disordered phase is mainly distributed in the middle and
      the bottom of the films.

PMID- 24590857
TI  - Metabolic flux analysis of plastidic isoprenoid biosynthesis in poplar leaves
      emitting and nonemitting isoprene.
AB  - The plastidic 2-C-methyl-D-erythritol-4-phosphate (MEP) pathway is one of the
      most important pathways in plants and produces a large variety of essential
      isoprenoids. Its regulation, however, is still not well understood. Using the
      stable isotope 13C-labeling technique, we analyzed the carbon fluxes through the
      MEP pathway and into the major plastidic isoprenoid products in isoprene-emitting
      and transgenic isoprene-nonemitting (NE) gray poplar (Populus*canescens). We
      assessed the dependence on temperature, light intensity, and atmospheric [CO2].
      Isoprene biosynthesis was by far (99%) the main carbon sink of MEP pathway
      intermediates in mature gray poplar leaves, and its production required
      severalfold higher carbon fluxes compared with NE leaves with almost zero
      isoprene emission. To compensate for the much lower demand for carbon, NE leaves
      drastically reduced the overall carbon flux within the MEP pathway. Feedback
      inhibition of 1-deoxy-D-xylulose-5-phosphate synthase activity by accumulated
      plastidic dimethylallyl diphosphate almost completely explained this reduction in
      carbon flux. Our data demonstrate that short-term biochemical feedback regulation
      of 1-deoxy-d-xylulose-5-phosphate synthase activity by plastidic dimethylallyl
      diphosphate is an important regulatory mechanism of the MEP pathway. Despite
      being relieved from the large carbon demand of isoprene biosynthesis, NE plants
      redirected only approximately 0.5% of this saved carbon toward essential
      nonvolatile isoprenoids, i.e. beta-carotene and lutein, most probably to
      compensate for the absence of isoprene and its antioxidant properties.

PMID- 24590858
TI  - Rice fertilization-Independent Endosperm1 regulates seed size under heat stress
      by controlling early endosperm development.
AB  - Although heat stress reduces seed size in rice (Oryza sativa), little is known
      about the molecular mechanisms underlying the observed reduction in seed size and
      yield. To elucidate the mechanistic basis of heat sensitivity and reduced seed
      size, we imposed a moderate (34 degrees C) and a high (42 degrees C) heat stress
      treatment on developing rice seeds during the postfertilization stage. Both
      stress treatments reduced the final seed size. At a cellular level, the moderate
      heat stress resulted in precocious endosperm cellularization, whereas severe heat
      stressed seeds failed to cellularize. Initiation of endosperm cellularization is
      a critical developmental transition required for normal seed development, and it
      is controlled by Polycomb Repressive Complex2 (PRC2) in Arabidopsis (Arabidopsis
      thaliana). We observed that a member of PRC2 called Fertilization-Independent
      Endosperm1 (OsFIE1) was sensitive to temperature changes, and its expression was
      negatively correlated with the duration of the syncytial stage during heat
      stress. Seeds from plants overexpressing OsFIE1 had reduced seed size and
      exhibited precocious cellularization. The DNA methylation status and a repressive
      histone modification of OsFIE1 were observed to be temperature sensitive. Our
      data suggested that the thermal sensitivity of seed enlargement could partly be
      caused by altered epigenetic regulation of endosperm development during the
      transition from the syncytial to the cellularized state. 

PMID- 24590860
TI  - Measuring motion trajectories of particle swarms in flight.
AB  - We propose a novel dual optimization framework for measuring motion trajectories
      of large swarms of natural particles, in which a continuous objective model is
      defined in form of energy to approximate faithfully the behaviors of moving
      targets. Following the Lagrange dual decomposition strategy, the framework
      distributes the optimization problem into simple subproblems, each of which also
      approximate different behavior of targets respectively. With this "realistic"
      energy, the proposed scheme can approximate the underlying posterior of problems
      faithfully, while avoiding discretization errors. The new framework will take
      advantage of the complementary natures of subproblems, which will reduce
      ambiguity significantly while evading error propagation. Our experiments involve
      challenging datasets and demonstrate that our method can achieve results
      comparable to other state-of-the-art approaches. 

PMID- 24590861
TI  - Chemotherapy-induced peripheral neurotoxicity: a critical analysis.
AB  - With a 3-fold increase in the number of cancer survivors noted since the 1970s,
      there are now over 28 million cancer survivors worldwide. Accordingly, there is a
      heightened awareness of long-term toxicities and the impact on quality of life
      following treatment in cancer survivors. This review will address the increasing
      importance and challenge of chemotherapy-induced neurotoxicity, with a focus on
      neuropathy associated with the treatment of breast cancer, colorectal cancer,
      testicular cancer, and hematological cancers. An overview of the diagnosis,
      symptomatology, and pathophysiology of chemotherapy-induced peripheral neuropathy
      will be provided, with a critical analysis of assessment strategies,
      neuroprotective approaches, and potential treatments. The review will concentrate
      on neuropathy associated with taxanes, platinum compounds, vinca alkaloids,
      thalidomide, and bortezomib, providing clinical information specific to these
      chemotherapies.

PMID- 24590862
TI  - An examination of the scope and stereochemistry of the Ireland-Claisen
      rearrangement of boron ketene acetals.
AB  - The Ireland-Claisen rearrangement of boron ketene acetals is described. The boron
      ketene acetal intermediates are formed through a soft enolization that obviates
      the use of strong bases and the intermediacy of alkali metal enolates. Yields and
      diastereoselectivities of these rearrangements are very sensitive to the choice
      of boron reagent, even among those that have been shown to effect quantitative
      formation of boron ketene acetals from esters. The rearrangement occurs at room
      temperature for all substrates with generally high levels of stereoselectivity.
      In contrast to previous reports using boron triflates, the use of a commercially
      available boron iodide reagent allows for a wider substrate scope that extends to
      propionates and arylacetates, as well as the previously described alpha
      oxygenated esters. This work also provides insight into the dynamic nature of
      boron ketene acetals and the ramifications of this behavior for reactions in
      which they are intermediates. 

PMID- 24590863
TI  - Effect of crude extract of Eugenia jambolana Lam. on human cytochrome P450
      enzymes.
AB  - The fruit of Eugenia jambolana Lam. is very popular for its anti-diabetic
      property. Previous studies on the crude extract of E. jambolana (EJE) have
      successfully explored the scientific basis for some of its traditional medicinal
      uses. Considering its wide use and consumption as a seasonal fruit, the present
      study investigates the ability of E. jambolana to interact with cytochrome P450
      enzymes. The standardized EJE was incubated with pooled human liver microsomes to
      assess the CYP2C9-, CYP2D6-, and CYP3A4-mediated metabolism of diclofenac,
      dextromethorphan, and testosterone, respectively. The metabolites formed after
      the enzymatic reactions were quantified by high performance liquid
      chromatography. EJE showed differential effect on cytochrome P450 activities with
      an order of inhibitory potential as CYP2C9 > CYP3A4 > CYP2D6 having IC50 of
      76.69, 359.02, and 493.05 ug/mL, respectively. The selectivity of EJE for CYP2C9
      rather than CYP3A4 and CYP2D6 led to perform the enzyme kinetics to explicate the
      mechanism underlying the inhibition of CYP2C9-mediated diclofenac 4'
      hydroxylation. EJE was notably potent in inhibiting the reaction in a non
      competitive manner with Ki of 84.85 +/- 5.27 ug/mL. The results revealed the
      CYP2C9 inhibitory potential of EJE with lower Ki value suggesting that EJE should
      be examined for its potential pharmacokinetic and pharmacodynamic interactions
      when concomitantly administered with other drugs.

PMID- 24590859
TI  - Chronic functional bowel syndrome enhances gut-brain axis dysfunction,
      neuroinflammation, cognitive impairment, and vulnerability to dementia.
AB  - The irritable bowel syndrome (IBS) is a common chronic functional
      gastrointestinal disorder world wide that lasts for decades. The human gut
      harbors a diverse population of microbial organisms which is symbiotic and
      important for well being. However, studies on conventional, germ-free, and obese
      animals have shown that alteration in normal commensal gut microbiota and an
      increase in pathogenic microbiota-termed "dysbiosis", impact gut function,
      homeostasis, and health. Diarrhea, constipation, visceral hypersensitivity, and
      abdominal pain arise in IBS from the gut-induced dysfunctional metabolic, immune,
      and neuro-immune communication. Dysbiosis in IBS is associated with gut
      inflammation. Gut-related inflammation is pivotal in promoting endotoxemia,
      systemic inflammation, and neuroinflammation. A significant proportion of IBS
      patients chronically consume alcohol, non-steroidal anti-inflammatories, and
      fatty diet; they may also suffer from co-morbid respiratory, neuromuscular,
      psychological, sleep, and neurological disorders. The above pathophysiological
      substrate is underpinned by dysbiosis, and dysfunctional bidirectional "Gut-Brain
      Axis" pathways. Pathogenic gut microbiota-related systemic inflammation (due to
      increased lipopolysaccharide and pro-inflammatory cytokines, and barrier
      dysfunction), may trigger neuroinflammation enhancing dysfunctional brain regions
      including hippocampus and cerebellum. These as well as dysfunctional vago-vagal
      gut-brain axis may promote cognitive impairment. Indeed, inflammation is
      characteristic of a broad spectrum of neurodegenerative diseases that manifest
      demntia. It is argued that an awareness of pathophysiological impact of IBS and
      implementation of appropriate therapeutic measures may prevent cognitive
      impairment and minimize vulnerability to dementia. 

PMID- 24590864
TI  - Selective inhibition of mutant Ras protein through covalent binding.
AB  - One of the first oncogenes to be discovered and one of the most prevalently
      mutated tumor genes is Ras. Shokat et al. and Gray et al. have succeeded in
      discovering allosteric inhibitors and inhibitory nucleotide analogues,
      respectively, of K-Ras proteins that covalently and selectively bind G12C-mutant
      K-Ras. These strategies of specifically targeting a mutant form of Ras may offer
      an opportunity for cancer-selective therapies that spare normal tissue. 

PMID- 24590865
TI  - Breast cancer nodal metastasis correlates with tumour and lymph node methylation
      profiles of Caveolin-1 and CXCR4.
AB  - DNA methylation is the best characterised epigenetic change so far. However, its
      role in breast cancer metastasis has not as yet been elucidated. The aim of this
      study was to investigate the differences between the methylation profiles
      characterising primary tumours and their corresponding positive or negative for
      metastasis lymph nodes (LN) and correlate these with tumour metastatic potential.
      Methylation signatures of Caveolin-1, CXCR4, RAR-beta, Cyclin D2 and Twist gene
      promoters were studied in 30 breast cancer primary lesions and their
      corresponding metastasis-free and tumour-infiltrated LN with Methylation-Specific
      PCR. CXCR4 and Caveolin-1 expression was further studied by immunohistochemistry.
      Tumours were typified by methylation of RAR-beta and hypermethylation of Cyclin
      D2 and Twist gene promoters. Tumour patterns were highly conserved in tumour
      infiltrated LN. CXCR4 and Caveolin-1 promoter methylation patterns differentiated
      between node-negative and metastatic tumours. Nodal metastasis was associated
      with tumour and lymph node profiles of extended methylation of Caveolin-1 and
      lack of CXCR4 hypermethylation. Immunodetection studies verified CXCR4 and
      Caveolin-1 hypermethylation as gene silencing mechanism. Absence of Caveolin-1
      expression in stromal cells associated with tumour aggressiveness while strong
      Caveolin-1 expression in tumour cells correlated with decreased 7-year disease
      free survival. Methylation-mediated activation of CXCR4 and inactivation of
      Caveolin-1 was linked with nodal metastasis while intratumoral Caveolin-1
      expression heterogeneity correlated with disease progression. This evidence
      contributes to the better understanding and, thereby, therapeutic management of
      breast cancer metastasis process.

PMID- 24590866
TI  - A systematic review on patient-reported outcomes in cancer survivors of
      randomised clinical trials: direction for future research.
AB  - OBJECTIVE: With increasing expectations of a 5-year survival rate among cancer
      patients, there is growing interest in patient-reported outcome (PRO) measures,
      particularly measures of health-related quality of life (HRQOL) in cancer
      practice. The purpose of this review was to explore the existing interventions
      for patients coping with cancer in terms of intervention type, PRO measurements
      and outcomes; and to identify directions for future research. METHODS: Systematic
      review of randomised clinical trials. A systematic search of four databases was
      conducted to identify articles published in English or Chinese from January 2000
      to July 2013. Studies were located using an electronic search, a manual search
      and an author search. RESULTS: A total of 34 articles corresponding to 33
      original studies were identified and included in this review. These interventions
      were classified under four broad categories according to their approaches: psycho
      education (15), case management (13), exercise (4) and feedback of PRO (1). The
      PRO measures covered different types of PRO measures, including HRQOL, functional
      status, symptom status, overall well-being and satisfaction with care. Positive
      outcomes of more than 70% (24) out of these interventions were reported.
      CONCLUSIONS: These findings highlight the significant outcomes of cancer patient
      interventions that applied PRO measures to evaluate their outcomes. A theory
      driven and careful design of the programme should be considered in the whole
      process of developing, delivering and assessing the programmes. Collaboration
      among patients, clinicians, researchers and policy makers is crucial to ensure
      the development of effective and accessible interventions targeting improving
      cancer survivors' HRQOL.

PMID- 24590867
TI  - Methylation epigenotypes and genetic features in colorectal laterally spreading
      tumors.
AB  - Aberrant DNA methylation plays an important role in genesis of colorectal cancer
      (CRC). Previously, we identified Group 1 and Group 2 methylation markers through
      genome-wide DNA methylation analysis, and classified CRC and protruded adenoma
      into three distinct clusters: high-, intermediate- and low-methylation
      epigenotypes. High-methylation epigenotype strongly correlated with BRAF
      mutations and these aberrations were involved in the serrated pathway, whereas
      intermediate-methylation epigenotype strongly correlated with KRAS mutations.
      Here, we investigated laterally spreading tumors (LSTs), which are flat, early
      CRC lesions, through quantitative methylation analysis of six Group 1 and 14
      Group 2 methylation markers using pyrosequencing. Gene mutations in BRAF, KRAS
      and PIK3CA, and immunostaining of TP53 and CTNNB1 as well as other
      clinicopathological factors were also evaluated. By hierarchical clustering using
      methylation information, LSTs were classified into two subtypes; intermediate
      methylation epigenotype correlating with KRAS mutations (p = 9 * 10(-4)) and a
      granular morphology (LST-G) (p = 1 * 10(-7)), and low-methylation epigenotype
      correlating with CTNNB1 activation (p = 0.002) and a nongranular morphology (LST
      NG) (p = 1 * 10(-7)). Group 1 marker methylation and BRAF mutations were barely
      detected, suggesting that high-methylation epigenotype was unlikely to be
      involved in LST development. TP53 mutations correlated significantly with
      malignant transformation, regardless of epigenotype or morphology type. Together,
      this may suggest that two molecular pathways, intermediate methylation associated
      with KRAS mutations and LST-G morphology, and low methylation associated with
      CTNNB1 activation and LST-NG morphology, might be involved in LST development,
      and that involvement of TP53 mutations could be important in both subtypes in the
      development from adenoma to cancer.

PMID- 24590868
TI  - Severe liver injury while using umbilical venous catheter: case series and
      literature review.
AB  - OBJECTIVE: Proper position of umbilical venous catheter (UVC) is of importance to
      avoid severe complications. We review clinical presentations of neonates with UVC
      who developed catheter-associated liver injury. STUDY DESIGN: We reviewed
      institutional intensive care database (2008-2013) and identified neonates with
      UVCs who developed severe hepatic injury. We recorded admission diagnosis,
      gestational age, birth weight, number of days the umbilical catheter was in
      place, its radiological position at insertion and at the time of injury,
      presenting clinical signs, and outcomes. RESULTS: Of 1,081 neonates, 9 (0.8% [95%
      exact binomial confidence interval, 0.4-1.6%]) with UVC developed severe hepatic
      injury. All had the UVC malpositioned within the liver circulation. All
      presentations were life threatening, with acute abdominal distension
      (hepatomegaly) being the most consistent sign. Two neonates died from
      complications which were unrelated to catheter-associated liver injury.
      CONCLUSIONS: In all neonates with liver injury, UVC was malpositioned within the
      portal circulation. Despite the fact that our report provides only circumstantial
      evidence for the mechanism of injury, it supports reports which suggest that
      "low" UVC position increases potential for this type of complication. Acute onset
      of abdominal distension in a neonate with UVC should prompt ultrasonographic
      evaluation of position of the catheter tip.

PMID- 24590869
TI  - SHARP edges: recovering cortical phase contrast through harmonic extension.
AB  - PURPOSE: To recover local phase contrast at the edges of the brain (e.g.,
      cortex), where it is otherwise unavailable with the conventional form of the
      technique sophisticated harmonic artifact reduction for phase data (SHARP).
      METHODS: A harmonic potential field, such as the magnetic "background" field, is
      an analytic field and can thus be represented by a convergent power series. Using
      SHARP to obtain an initial estimate of the harmonic background field over a
      reduced inner portion of the brain, a three-dimensional Taylor expansion was
      performed to extend field coverage to the brain edges. The method, called
      Extended-SHARP, was quantitatively assessed through a numerical field-forward
      simulation and qualitatively demonstrated in vivo. RESULTS: Using a typical
      spherical kernel (6 mm radius), Extended-SHARP recovered on average 26% more in
      vivo brain volume than SHARP. When applied to the numerical model, local field
      contrast around an otherwise lost edge source was recovered, with the resulting
      error comparable to that of conventional SHARP. CONCLUSION: The lost field values
      near the edges of the brain can be recovered through an easily implemented
      adaptation to conventional SHARP.

PMID- 24590870
TI  - Photophysical evidence of charge-transfer-complex pairs in mixed-linker 5-amino/5
      nitroisophthalate CAU-10.
AB  - The photochemistry of two isostructural metal-organic frameworks based on 5
      amino/5-formamidoisophthalate (CAU-10-NH2 /NHCHO) or mixed-linker 5-amino/5
      formamido- and 5-nitroisophthalate (CAU-10-NO2 /NH2 /NHCHO) has been studied
      using laser flash photolysis. 355 nm excitation of CAU-10-NH2 /NHCHO leads to a
      transient absorption spectrum characterized by a broad continuous absorption from
      380 to 800 nm that was attributed to the presence of holes (440 nm) and electrons
      (600 nm) based on iPrOH and N2 O quenching, respectively. In contrast, no
      transients were observed for the isostructural mixed-linker CAU-10-NO2 /NH2
      /NHCHO, data that is compatible with the uniform distribution of linkers 5
      amino/5-formamido/5-nitroisophthalate as charge-transfer complex pairs. The same
      effect of quenching of 5-aminoisophthalate transients by 5-nitroisophthalate was
      also observed in aqueous solution (pH 9) but with much lower strength. Using a
      simple Stern-Volmer formalism allowed the estimation of the interaction of 5
      aminoisophthalate with 5-nitroisophthalate in MOF to be 5.2*10(4) times stronger
      than in the aqueous phase. 

PMID- 24590871
TI  - EEG Synchronization Evaluation: A New Diagnostic Tool for Predicting the
      Progression of Alzheimer's disease.
AB  - Alzheimer's disease (AD) is known as a leading cause of dementia in elderly
      persons. It is a chronic neurodegenerative disorder characterized by progressive
      cognitive dysfunction. AD can disrupt functional connectivity in distributed
      cortical networks. The S-estimator, which is a measure of multivariate
      intraregional synchronization, was analyzed in this study. Twenty patients with
      AD and 20 age-matched controls were tested at baseline and after 1 year to
      evaluate the potential of synchronization to be a possible marker of AD
      progression. All the subjects had clinical evaluations and electroencephalography
      (EEG) at baseline and post 1 year. Hyposynchronization had an important effect in
      the medial temporal and frontal regions, while there were no significant effects
      for hypersynchronization. Hypersynchronized clusters changed more slowly with
      time (P = .067), whereas hyposynchronized clusters changed more quickly (P =
      .032). Hyposynchronized cluster-averaged S-estimator correlated negatively with
      progression of AD (r = -0.98769, P = .0103). In conclusion, the present study
      provides a whole-brain, AD-specific phenotype of temporal coordination in
      distributed cortical networks, which is an early diagnostic tool for progression
      of AD. 

PMID- 24590872
TI  - LORETA Neurofeedback in the Precuneus: Operant Conditioning in Basic Mechanisms
      of Self-Regulation.
AB  - Low-resolution brain electomagnetic tomography (LORETA) neurofeedback provides a
      mechanism to influence the electrical activity of the brain in intracranial
      space. The aim of this study was to determine the effects of LORETA neurofeedback
      (LNFB) in the precuneus as a mechanism for improving self-regulation in controls
      and a heterogeneous diagnostic group (DX). Thirteen participants completed
      between 10 and 20 sessions of LNFB training in a 3-voxel cluster in the left
      precuneus. The participants included 5 nonclinical university students, and 8
      adults with heterogeneous psychiatric diagnoses. We assessed the effects of LNFB
      with neurophysiological measures as well as pre- and post-Personality Assessment
      Inventory (PAI) subscales and selected subtests from the Delis-Kaplan Executive
      Function System (DKEFS). There was a significant total relative power increase at
      the precuneus for baseline contrasts for the control group. The DX group did not
      reach significant levels. All participants showed improvements in executive
      functions and tended to report significantly less psychopathology. The basic
      neural mechanisms of self-regulation are poorly understood. The data obtained in
      this study demonstrate that LNFB in a heterogeneous population enhances executive
      functions while concordantly decreasing endorsement of psychological symptoms.
      The alpha frequency in the brain may represent integrative functioning relative
      to operant efficiency and self-regulatory mechanisms.

PMID- 24590873
TI  - Periodic Lateralized Epileptiform Discharges Associated With Irreversible
      Hyperglycemic Hemichorea-Hemiballism.
AB  - Periodic lateralized epileptiform discharges (PLEDs) on electroencephlography
      (EEG) usually indicate an acute, diffuse, and severe cerebral insult. Although
      hyperglycemic hemichorea-hemiballisum (HCHB) and striatal hyperintensity on T1
      weighted magnetic resonance (MR) images is an accepted clinical entity, PLEDs
      have not previously been reported. Herein, we report a 74-year-old man with
      hyperglycemic HCHB, hyperintense putamen on T1-MR images and PLEDs on EEG.
      Aggressive sugar control with neuroleptic treatment only slightly improved the
      severity of HCHB. We also tried titrated oral and intravenous haloperidol,
      clonazepam, and propranolol sequentially and in combination; however, the effects
      were poor. Unlike the generally reversibility of hyperglycemic HCHB, the
      condition was still present 6 months later. Hyperglycemia can cause HCHB and
      produce subcortical type-PLEDs, which may explain the findings in our patient. In
      conclusion, PLEDs can be found in patients with hyperglycemic HCHB and striatal
      hyperintensity on T1-weighted MR images, and the appearance of PLEDs may indicate
      an irreversible outcome. EEG should be considered in such circumstances.

PMID- 24590874
TI  - Phase Synchronization and Spectral Coherence Analysis of EEG Activity During
      Mental Fatigue.
AB  - In this article, 2 synchronization measures, phase locking value (PLV) and
      spectral coherence value (SCV), are used to characterize the changes of the phase
      synchronization and functional coupling of electroencephalogram (EEG) waves at
      different brain cortical areas for mental fatigue caused by a long-term cognitive
      task. The long-term cognitive task induces a significant decrease in the
      interhemispheric SCVs and PLVs of beta in central and parietal regions, a
      significant decrease in the intrahemispheric SCVs and PLVs of beta frequency band
      at the frontal-parietal and central-parietal, and frontal-central middle
      electrode pairs, suggesting EEG decreases in cooperative processing, strength of
      functional coupling, and flux of mutual information exchange in the corresponding
      inter- and intrahemispheres. However, when the mental fatigue level increases,
      the interhemispheric PLVs of theta are enhanced in the frontal region and C3-Cz
      electrode pair, and the intrahemispheric PLVs of theta are heightened at frontal
      central middle electrode pairs. PLV and SCV measures could reflect the changes of
      the phase synchronization and functional coupling of EEG waves from time and
      frequency domains, which are sensitive to mental fatigue. Therefore, PLVs and
      SCVs can provide an effective and reliable way to quantify brain response to
      mental fatigue.

PMID- 24590875
TI  - Nuclease-stimulated homologous recombination at the human beta-globin gene.
AB  - BACKGROUND: Mutations in the beta-globin gene (HBB) cause haemoglobinopathies
      where current treatments have serious limitations. Gene correction by homologous
      recombination (HR) is an attractive approach to gene therapy for such diseases
      and is stimulated by gene-specific endonucleases, including zinc finger nucleases
      (ZFNs). Customised nucleases targeting HBB have previously been shown to promote
      HR-mediated HBB modification in 0.3-60% of drug-selected cells, although
      frequencies among unselected cells, more relevant to the goal of correcting HBB
      in primary stem cells, have not been reported. METHODS: ZFNs targeting HBB were
      tested for HBB binding (two-hybrid assay) or HBB cleavage followed by inaccurate
      end joining (surveyor assay)in bacteria or human cancer cell lines, respectively.
      ZFN-stimulated HR was measured in cell lines by a modified fluorescence-based
      reporter assay or by targeted insertion of a drug-resistance marker into
      endogenous HBB confirmed by Southern analyses. RESULTS: Although the ZFNs that we
      assembled in-house showed limited potential, a commercially commissioned nuclease
      (ZFN4) enhanced HR mediated HBB modification in up to 95% of drug-selected cells.
      Among unselected cells, however, this frequency was less than 0.2%. Furthermore,
      ZFN4 cleaved HBB at an efficiency of 1-2% (surveyor assay) and enhanced the HR
      reporter assay 20-fold less efficiently than a control endonuclease. CONCLUSIONS:
      With ZFN4, we achieved higher efficiencies of HR-mediated HBB modification than
      previously reported for drug-selected cells. Our measurements of ZFN4-induced HR
      in unselected cells, however, suggest that improved nucleases must be developed
      if therapeutic HBB correction is to be achievable in primary stem cells.

PMID- 24590877
TI  - Predicting nonlinear pharmacokinetics of omeprazole enantiomers and racemic drug
      using physiologically based pharmacokinetic modeling and simulation: application
      to predict drug/genetic interactions.
AB  - PURPOSE: The objective of this study is to develop a physiologically-based
      pharmacokinetic (PBPK) model for each omeprazole enantiomer that accounts for
      nonlinear PK of the two enantiomers as well as omeprazole racemic drug. METHODS:
      By integrating in vitro, in silico and human PK data, we first developed PBPK
      models for each enantiomer. Simulation of racemic omeprazole PK was accomplished
      by combining enantiomer models that allow mutual drug interactions to occur.
      RESULTS: The established PBPK models for the first time satisfactorily predicted
      the nonlinear PK of esomeprazole, R-omeprazole and the racemic drug. The modeling
      exercises revealed that the strong time-dependent inhibition of CYP2C19 by
      esomeprazole greatly altered the R-omeprazole PK following administration of
      racemic omeprazole as in contrast to R-omeprazole given alone. When PBPK models
      incorporated both autoinhibition of each enantiomer and mutual interactions, the
      ratios between predicted and observed AUC following single and multiple dosing of
      omeprazole were 0.97 and 0.94, respectively. CONCLUSIONS: PBPK models of
      omeprazole enantiomers and racemic drug were developed. These models can be
      utilized to assess CYP2C19-mediated drug and genetic interaction potential for
      omeprazole and esomeprazole.

PMID- 24590878
TI  - Early diagnosis of orthopedic implant failure using macromolecular imaging
      agents.
AB  - PURPOSE: To develop and evaluate diagnostic tools for early detection of wear
      particle-induced orthopaedic implant loosening. METHODS: N-(2
      Hydroxypropyl)methacrylamide (HPMA) copolymer was tagged with a near infrared dye
      and used to detect the inflammation induced by polymethylmethacrylate (PMMA)
      particles in a murine peri-implant osteolysis model. It was established by
      inserting an implant into the distal femur and challenging with routine PMMA
      particles infusion. The osteolysis was evaluated by micro-CT and histological
      analysis at different time points. RESULTS: Significant peri-implant osteolysis
      was found 3-month post PMMA particle challenge by micro-CT and histological
      analysis. At 1-month post challenge, when there was no significant peri-implant
      bone loss, the HPMA copolymer-near infrared dye conjugate was found to
      specifically target the femur with PMMA particles deposition, but not the
      contralateral control femur with phosphate buffered saline (PBS) infusion.
      CONCLUSION: The results from this study demonstrate the feasibility of utilizing
      the macromolecular diagnostic agent to detect particle-induced peri-implant
      inflammation prior to the development of detectable osteolysis. Recognition of
      this early pathological event would provide the window of opportunity for
      prevention of peri-implant osteolysis and subsequent orthopaedic implant failure.

PMID- 24590879
TI  - Directed self-assembled nanoparticles of probucol improve oral delivery:
      fabrication, performance and correlation.
AB  - PURPOSE: We are reporting on the development of a unique drug delivery platform
      by directed self-assembly technique to improve the oral delivery of hydrophobic
      drugs. METHODS: Herein, a series of probucol directed self-assembled
      nanoparticles (PDN) were developed with two components of probucol and surfactant
      such as Tween 20, Tween 80, D-alpha-tocopheryl polyethylene glycol 1,000
      succinate (TPGS) and HS-15, which was respectively named as T20-PDN, T80-PDN, TP
      PDN and HS-PDN. The formation of various PDNs was determined by in vitro
      characterization and the physicochemical properties of these PDNs were
      determined. Moreover, the performance of PDN in enhancing the oral delivery and
      possible correlation between the in vitro properties and in vivo performances
      were investigated. RESULTS: PDN was homogenous nanometer-sized particles with
      negative surface charge. The cellular uptake of probucol in Caco-2 cell monolayer
      was respectively increased 1.15, 1.82, 1.59 and 5.31-fold by these PDN. In
      particular, the oral bioavailability of these PDN was significantly improved 3.0,
      4.1, 5.4 and 10.4 folds compared with the free drug suspension. The enhanced
      cellular uptake and oral bioavailability were correlated with the characters of
      involved surfactants and the particle size of PDN. CONCLUSIONS: Thereby, the
      directed self-assembled nanoparticles could provide a new strategy for enhancing
      the oral delivery of hydrophobic drugs.

PMID- 24590880
TI  - A mechanism enhancing macromolecule transport through paracellular spaces induced
      by Poly-L-Arginine: Poly-L-Arginine induces the internalization of tight junction
      proteins via clathrin-mediated endocytosis.
AB  - PURPOSE: Poly-L-arginine (PLA) enhances the paracellular permeability of the Caco
      2 cell monolayer to hydrophilic macromolecules by disappearance of tight junction
      (TJ) proteins from cell-cell junctions. However, the mechanism of the
      disappearance of TJ proteins in response to PLA has been unclear. In this study,
      we investigated the mechanism of disappearance of TJ proteins from cell-cell
      junctions after the application of PLA to Caco-2 cell monolayers. METHODS: The
      membrane conductance (Gt), FITC-dextran (FD-4) permeability, and localization of
      TJ proteins were examined after the treatment of Caco-2 cell monolayers with PLA
      in the presence of various endocytosis inhibitors. In addition, the localization
      of endosome marker proteins was also observed. RESULTS: Clathrin-mediated
      endocytosis inhibitors suppressed the increase in Gt and Papp of FD-4 induced by
      PLA, and also significantly suppressed the disappearance of TJ proteins induced
      by PLA. Furthermore, occludin, one of the TJ proteins, colocalized with early
      endosome and recycling endosomes after the internalization of occludin induced by
      PLA, and then was recycled to the cell-cell junctions. CONCLUSION: PLA induced
      the transient internalization of TJ proteins in cell-cell junctions via clathrin
      mediated endocytosis, subsequently increasing the permeability of the Caco-2 cell
      monolayer to FD-4 via a paracellular route.

PMID- 24590881
TI  - Investigation of the effect of hydroxypropyl methylcellulose on the phase
      transformation and release profiles of carbamazepine-nicotinamide cocrystal.
AB  - PURPOSE: The aim of this work was to investigate the influence of hydroxypropyl
      methylcellulose (HPMC) on the phase transformation and release profile of
      carbamazepine-nicotinamide (CBZ-NIC) cocrystal in solution and in sustained
      release matrix tablets. METHODS: The polymorphic transitions of the CBZ-NIC
      cocrystal and its crystalline properties were examined by differential scanning
      calorimetry (DSC), X-ray powder diffraction (XRPD), Raman spectroscopy, and
      scanning electron microscopy (SEM). RESULTS: The apparent CBZ solubility and
      dissolution rate of CBZ-NIC cocrystal were constant in different concentrations
      of HPMC solutions. In a lower percentage of HPMC in the matrix tablets, the CBZ
      release profile of the CBZ-NIC cocrystal was nonlinear and declined over time.
      With an increased HPMC content in the tablets, the CBZ-NIC cocrystal formulation
      showed a significantly higher CBZ release rate in comparison with the other two
      formulations of CBZ III and the physical mixture. CONCLUSIONS: Because of a
      significantly improved dissolution rate of the CBZ-NIC cocrystal, the rate of CBZ
      entering into solution is significantly faster than the rate of formation of the
      CBZ-HPMC soluble complex in solution, leading to a higher supersaturation level
      of CBZ and subsequently precipitation of CBZ dihydrate.

PMID- 24590882
TI  - Impact of airborne particle size, acoustic airflow and breathing pattern on
      delivery of nebulized antibiotic into the maxillary sinuses using a realistic
      human nasal replica.
AB  - PURPOSE: Improvement of clinical outcome in patients with sinuses disorders
      involves targeting delivery of nebulized drug into the maxillary sinuses. We
      investigated the impact of nebulization conditions (with and without 100 Hz
      acoustic airflow), particle size (9.9 MUm, 2.8 MUm, 550 nm and 230 nm) and
      breathing pattern (nasal vs. no nasal breathing) on enhancement of aerosol
      delivery into the sinuses using a realistic nasal replica developed by our team.
      METHODS: After segmentation of the airways by means of high-resolution computed
      tomography scans, a well-characterized nasal replica was created using a rapid
      prototyping technology. A total of 168 intrasinus aerosol depositions were
      performed with changes of aerosol particle size and breathing patterns under
      different nebulization conditions using gentamicin as a marker. RESULTS: The
      results demonstrate that the fraction of aerosol deposited in the maxillary
      sinuses is enhanced by use of submicrometric aerosols, e.g. 8.155 +/- 1.476 mg/L
      of gentamicin in the left maxillary sinus for the 2.8 MUm particles vs. 2.056 +/-
      0.0474 for the 550 nm particles. Utilization of 100-Hz acoustic airflow
      nebulization also produced a 2- to 3-fold increase in drug deposition in the
      maxillary sinuses (e.g. 8.155 +/- 1.476 vs. 3.990 +/- 1.690 for the 2.8 MUm
      particles). CONCLUSIONS: Our study clearly shows that optimum deposition was
      achieved using submicrometric particles and 100-Hz acoustic airflow nebulization
      with no nasal breathing. It is hoped that our new respiratory nasal replica will
      greatly facilitate the development of more effective delivery systems in the
      future.

PMID- 24590883
TI  - Comprehensive cytogenetic and molecular cytogenetic analysis of 44 Burkitt
      lymphoma cell lines: secondary chromosomal changes characterization, karyotypic
      evolution, and comparison with primary samples.
AB  - Burkitt lymphoma cell lines (BL-CL) are used extensively as in vitro models in
      genetic studies; however, cytogenetic information is not always available or
      updated. We provide a comprehensive cytogenetic resource of 44 BL-CL, assessed by
      G-banding, multicolor-FISH, and FISH with 1q, 3p, 7q, and 13q region-specific
      probes, including the first cytogenetic characterization of 22 BL-CL and the
      revision of further 22 commonly used BL-CL. Based on these data, we determined a
      consensus karyotype, evaluated in detail the secondary chromosomal changes (SCC),
      and the karyotypic stability of these cell lines. An individual karyotype was
      identified in all investigated BL-CL, confirming their unique origin. Most of the
      BL-CL remained cytogenetically relative stable after years of intensive
      cultivation. The most frequent structural SCC were dup(1q), del(13q) and the most
      frequent numerical SCC were +7, +13. Common breakpoints were located on 1q12,
      7q11, and 13q31. The most common gains were in 1q and 7q and the most common
      losses were in 11q and 13q. Interestingly, the frequency of 1q gains and 13q
      losses was significantly higher in the EBV-negative than in the EBV-positive BL
      CL. Furthermore, by reviewing karyotypes of 221 primary BL listed in the Mitelman
      database, we observed similarities between BL-CL and primary BL regarding the
      frequency of numerical and structural SCC and breakpoint distribution. In BL-CL
      and in primary BL two SCC, dup(1q), and +12, always occurred mutually exclusive
      of each other. These findings validate BL-CL as appropriate model for in vitro
      studies on the significance of SCC in the pathogenesis of BL.

PMID- 24590885
TI  - Natural killer cells: the secret weapon in dendritic cell vaccination strategies.
AB  - In cancer therapy, dendritic cell (DC) vaccination is still being explored.
      Clinical responses, however, are diverse and there is a lack of immunologic
      readout systems that correspond with clinical outcome. Only in the minority of
      patients, T-cell responses correlate with clinical outcome, indicating that other
      immune cells also gain anticancer activity. We still have limited knowledge of
      the effect of DC vaccination on different immune effector cells. However, it has
      been shown that bidirectional cross-talk between natural killer (NK) cells and
      DCs is responsible for enhanced activation of both cell types and increases their
      antitumor activity. In this review, we postulate the possibility that NK cells
      are the secret weapons in DC vaccination and studying their behavior together
      with T-cell activation in vaccinated individuals might predict clinical outcome.

PMID- 24590886
TI  - About CD45-/CD31+/CD105+ circulating cells in patients with gynecologic
      malignancies--letter.

PMID- 24590887
TI  - About CD45-/CD31+/CD105+ circulating cells in patients with gynecologic
      malignancies--response.

PMID- 24590888
TI  - Stromal responses among carcinomas--letter.

PMID- 24590889
TI  - Stromal responses among carcinomas--response.

PMID- 24590890
TI  - Absolute stereochemistry of a 4 a-hydroxyriboflavin analogue of the key
      intermediate of the FAD-monooxygenase cycle.
AB  - The biological action of flavoenzymes, such as flavin adenine dinucleotide (FAD)
      containing monooxygenase, involves the formation of oxygenated flavin
      derivatives, such as 4 a-hydroperoxyflavin and 4 a-hydroxyflavin, in which a new
      center of chirality is created at the 4 a position during the enzymatic
      reactions. So far, the absolute configuration of this center of chirality in
      natural 4 a-oxygenated flavins has remained unknown in spite of its key
      importance for the diverse functions of flavoenzymes. Herein, we report the 4 a
      hydroxy adduct 3 of 3-benzyl-5-ethyl-10-(tetraacetyl-D-ribityl)flavinium (1), one
      of the key intermediates involved in the enantioselective organocatalytic
      oxidation of sulfides to sulfoxides. The 4 a-hydroxyflavin diastereomers (+)-3
      and (-)-3, separated by HPLC, were characterized by electronic circular dichroism
      (CD) spectroscopy. Their absolute configurations at the 4 a position were, for
      the first time, determined by comparing experimental CD spectra with those
      calculated by means of time-dependent density functional theory (TDDFT) on DFT
      optimized structures obtained after an extensive conformation analysis. 

PMID- 24590891
TI  - Genome classification of Musa cultivars from northeast India as revealed by ITS
      and IRAP markers.
AB  - Genome classification of 38 banana cultivars found in northeast India was
      successfully carried out using polymerase chain reaction-restriction fragment
      length polymorphism (PCR-RFLP) of the internal transcribed spacer (ITS) region
      and inter-retrotransposon amplified polymorphism (IRAP) techniques. The RsaI
      digestion of the ITS region revealed the composition of A genome in 32 cultivars
      and B genome in 29 cultivars. With the gypsy-IRAP marker, 33 cultivars were
      identified to be composed of B genome. The AluI digestion of the 420-bp PCR
      amplification product using copia-IRAP primer resulted in the identification of
      the ABB genome in 17 cultivars. Overall, the data obtained from 36 cultivars
      using the molecular markers were in accordance with the initial classification
      based on morphological characters except in two cultivars. The present findings
      provide the reliable information on the genome classification and the status of
      the existing banana genetic resources from the northeastern Indian region, which
      could be utilized in improvement and conservation programs.

PMID- 24590892
TI  - Application of biosurfactant from Sphingobacterium spiritivorum AS43 in the
      biodegradation of used lubricating oil.
AB  - This study aimed at investigating the application of biosurfactant from
      Sphingobacterium spiritivorum AS43 using molasses as a substrate and fertilizer
      to enhance the biodegradation of used lubricating oil (ULO). The cell surface
      hydrophobicity of bacteria, the emulsification activity, and the biodegradation
      efficiency of ULO were measured. The bacterial adhesion in the hydrocarbon test
      was used to denote the cell surface hydrophobicity of the used bacterial species.
      The results indicate a strong correlation between cell surface hydrophobicity,
      emulsification activity, and the degree of ULO biodegradation. The maximum
      degradation of ULO (62 %) was observed when either 1.5 % (w/v) of biosurfactant
      or fertilizer was added. The results also revealed that biosurfactants alone are
      capable of promoting biodegradation to a large extent without added fertilizer.
      The data indicate the potential for biosurfactant production by using low-cost
      substrate for application in the bioremediation of soils contaminated with
      petroleum hydrocarbons or oils.

PMID- 24590893
TI  - Effects of chitosan on the protein profile of grape cell culture subcellular
      fractions.
AB  - Grapevine is a large source of healthy polyphenols for human diet, and red table
      grapes and wines are the main source of stilbenes. These compounds are important
      both in the plant defence system and for human health. In the present study,
      Vitis vinifera cv. Barbera cell cultures were treated with 50 MUg/mL chitosan and
      proteomic analyses on soluble and membrane subcellular fractions were performed
      against suitable controls. Three soluble stilbene synthase protein spots, four
      stilbene synthase spots in the microsomal fraction and four spots of membrane
      ATPase subunits were identified, the accumulation of which was modulated in
      response to chitosan treatment. Present proteomic and immunolocalisation data
      seem to provide evidence supporting the hypothesis that a stilbene biosynthetic
      multi-enzyme complex is associated with the intracellular membrane. In addition,
      proteomic analyses showed a general decrease in the accumulation of proteins
      belonging to different primary metabolism pathways, both in the soluble and
      membrane fractions. In particular, energy, sugar and amino acid metabolisms were
      down-regulated as a consequence of chitosan and acetic acid treatments. These
      metabolic modifications could lead to a consistent change in the profile and
      amount of metabolites stored in grape berries, with consequent effects on taste,
      flavour, organoleptic and nutraceutical properties of derived food products. 

PMID- 24590895
TI  - Regulation and function of the atypical cadherin FAT1 in hepatocellular
      carcinoma.
AB  - In human cancers, giant cadherin FAT1 may function both, as an oncogene and a
      tumor suppressor. Here, we investigated the expression and function of FAT1 in
      hepatocellular carcinoma (HCC). FAT1 expression was increased in human HCC cell
      lines and tissues compared with primary human hepatocytes and non-tumorous liver
      tissue as assessed by quantitative PCR and western blot analysis. Combined
      immunohistochemical and tissue microarray analysis showed a significant
      correlation of FAT1 expression with tumor stage and proliferation. Suppression of
      FAT1 expression by short hairpin RNA impaired proliferation and migration as well
      as apoptosis resistance of HCC cells in vitro. In nude mice, tumors formed by
      FAT1-suppressed HCC cells showed a delayed onset and more apoptosis compared with
      tumors of control cells. Both hepatocyte growth factor and hypoxia-mediated
      hypoxia-inducible factor 1 alpha activation were identified as strong inducers of
      FAT1 in HCC. Moreover, demethylating agents induced FAT1 expression in HCC cells.
      Hypoxia lead to reduced levels of the methyl group donor S-adenosyl-L-methionine
      (SAM) and hypoxia-induced FAT1 expression was inhibited by SAM supplementation in
      HCC cells. Together, these findings indicate that FAT1 expression in HCC is
      regulated via promotor methylation. FAT1 appears as relevant mediator of hypoxia
      and growth receptor signaling to critical tumorigenic pathways in HCC. This
      knowledge may facilitate the rational design of novel therapeutics against this
      highly aggressive malignancy.

PMID- 24590894
TI  - Myeloid Cell COX-2 deletion reduces mammary tumor growth through enhanced
      cytotoxic T-lymphocyte function.
AB  - Cyclooxygenase-2 (COX-2) expression is associated with poor prognosis across a
      range of human cancers, including breast cancer. The contribution of tumor cell
      derived COX-2 to tumorigenesis has been examined in numerous studies; however,
      the role of stromal-derived COX-2 is ill-defined. Here, we examined how COX-2 in
      myeloid cells, an immune cell subset that includes macrophages, influences
      mammary tumor progression. In mice engineered to selectively lack myeloid cell
      COX-2 [myeloid-COX-2 knockout (KO) mice], spontaneous neu oncogene-induced tumor
      onset was delayed, tumor burden reduced, and tumor growth slowed compared with
      wild-type (WT). Similarly, growth of neu-transformed mammary tumor cells as
      orthotopic tumors in immune competent syngeneic myeloid-COX-2 KO host mice was
      reduced compared with WT. By flow cytometric analysis, orthotopic myeloid-COX-2
      KO tumors had lower tumor-associated macrophage (TAM) infiltration consistent
      with impaired colony stimulating factor-1-dependent chemotaxis by COX-2 deficient
      macrophages in vitro. Further, in both spontaneous and orthotopic tumors, COX-2
      deficient TAM displayed lower immunosuppressive M2 markers and this was
      coincident with less suppression of CD8(+) cytotoxic T lymphocytes (CTLs) in
      myeloid-COX-2 KO tumors. These studies suggest that reduced tumor growth in
      myeloid-COX-2 KO mice resulted from disruption of M2-like TAM function, thereby
      enhancing T-cell survival and immune surveillance. Antibody-mediated depletion of
      CD8(+), but not CD4(+) cells, restored tumor growth in myeloid-COX-2 KO to WT
      levels, indicating that CD8(+) CTLs are dominant antitumor effectors in myeloid
      COX-2 KO mice. Our studies suggest that inhibition of myeloid cell COX-2 can
      potentiate CTL-mediated tumor cytotoxicity and may provide a novel therapeutic
      approach in breast cancer therapy. 

PMID- 24590896
TI  - Mirk/dyrk1B kinase is upregulated following inhibition of mTOR.
AB  - The PI3K/PTEN/Akt/mTOR/p70S6K pathway is one of the most frequently deregulated
      signaling pathways in solid tumors and has a functional role in drug resistance.
      However, targeting this pathway leads to compensatory activation of several
      mediators of cell survival. Expression of the reactive oxygen species-controlling
      kinase Mirk/dyrk1B was increased severalfold by the mammalian target of rapamycin
      (mTOR) inhibitors RAD001, WYE354 and rapamycin, with less effect by the Akt
      inhibitors AZD5363 and MK-2206. Upregulation of Mirk messenger RNA (mRNA)
      expression was mediated by cyclic AMP response element binding protein (CREB)
      binding to two sites in the Mirk promoter upstream of the transcription start
      site and one site within exon 4. Depletion of CREB reduced Mirk expression,
      whereas depletion of mTOR increased it. Moreover, hydroxytamoxifen activation of
      an Akt-estrogen receptor construct blocked an increase in Mirk mRNA and protein.
      Addition of a Mirk/dyrk1B kinase inhibitor increased the sensitivity of Panc1
      pancreatic cancer cells and three different ovarian cancer cell lines to the mTOR
      inhibitor RAD001. Targeting Mirk kinase could improve the utility of mTOR
      inhibitors and so presents an attractive drug target. 

PMID- 24590897
TI  - Association between the p73 G4C14-to-A4T14 polymorphism and risk of
      nasopharyngeal carcinoma: a case-control and family-based study.
AB  - p73, a structural and functional homolog of p53, plays an important role in
      modulating cell cycle control and apoptosis. We examined whether the p73 G4C14-to
      A4T14 polymorphism was related to the risk of nasopharyngeal carcinoma (NPC)
      among Chinese populations. The G4C14-to-A4T14 polymorphism was genotyped in 593
      NPC cases and 480 controls, and in 102 NPC trios. Logistic regression analysis
      and transmission/disequilibrium tests (TDT) were performed to evaluate whether
      there was an association between the polymorphism and NPC, respectively.
      Functional analyses were conducted to verify the biological relevance of the
      polymorphism. We observed that compared with the GC/GC genotype, the genotypes
      containing AT allele (GC/AT + AT/AT genotypes) were associated with significantly
      increased susceptibility to NPC [odds ratio (OR) = 1.51; 95% confidence interval
      (CI) = 1.16-1.95; P = 0.002]. Furthermore, compared with the GC/GC genotype, the
      GC/AT + AT/AT genotypes were significantly associated with the advanced lymph
      node metastasis (OR = 1.47; 95% CI = 1.02-2.11; P = 0.041). A significantly
      greater than expected transmission of the AT allele from heterozygous parents to
      offspring was also observed (P = 0.049) using the TDT. By using the TdT-mediated
      dUPT-biotin nick end labeling assay, we observed lower apoptosis in NPC tissues
      from the AT allele carriers compared with that from non-carriers. Furthermore,
      the relative TAp73 RNA levels of the AT allele were lower than those of the GC
      allele in heterozygous cells. Our findings suggest that the p73 G4C14-to-A4T14
      polymorphism may play a role in mediating the susceptibility to NPC in Chinese
      populations. 

PMID- 24590898
TI  - A new structural motif for an enantiomerically pure metallosupramolecular Pd4L8
      aggregate by anion templating.
AB  - An enantiomerically pure BINOL-based bis(3-pyridyl) ligand 1 assembles into a
      homochiral [Pd4(1)8] complex upon coordination to tetravalent Pd(II) ions. The
      formation of this aggregate is templated by two tetrafluoroborate counterions
      that are encapsulated in two peripheral cavities. The resulting structure is a
      new structural motif for this kind of metallosupramolecular assemblies that
      arranges the palladium ions in a distorted tetrahedral fashion and forces ligand
      1 to adopt two different conformations. Both phenomena are unique and cause an
      overall three-dimensional structure that has another confined, chiral, and
      hydrophilic central cavity.

PMID- 24590899
TI  - Gastrointestinal bleeding.

PMID- 24590900
TI  - Oophorectomy can reduce ovarian cancer risk in women with BRCA mutations:
      patients benefit from counseling, support.

PMID- 24590901
TI  - Finasteride reduces cancer risk, does not increase death risk.

PMID- 24590902
TI  - New method to predict DCIS recurrence.

PMID- 24590903
TI  - Young women fearing recurrence opt for prophylactic mastectomy.

PMID- 24590904
TI  - Clinical predictors of survival in men with castration-resistant prostate cancer:
      evidence that Gleason score 6 cancer can evolve to lethal disease.

PMID- 24590906
TI  - A double-quadrature radiofrequency coil design for proton-decoupled carbon-13
      magnetic resonance spectroscopy in humans at 7T.
AB  - PURPOSE: Carbon-13 magnetic resonance spectroscopy ((13) C-MRS) is challenging
      because of the inherent low sensitivity of (13) C detection and the need for
      radiofrequency transmission at the (1) H frequency while receiving the (13) C
      signal, the latter requiring electrical decoupling of the (13) C and (1) H
      radiofrequency channels. In this study, we added traps to the (13) C coil to
      construct a quadrature-(13) C/quadrature-(1) H surface coil, with sufficient
      isolation between channels to allow simultaneous operation at both frequencies
      without compromise in coil performance. METHODS: Isolation between channels was
      evaluated on the bench by measuring all coupling parameters. The quadrature mode
      of the quadrature-(13) C coil was assessed using in vitro (23) Na gradient echo
      images. The signal-to-noise ratio (SNR) was measured on the glycogen and glucose
      resonances by (13) C-MRS in vitro, compared with that obtained with a linear-(13)
      C/quadrature-(1) H coil, and validated by (13) C-MRS in vivo in the human calf at
      7T. RESULTS: Isolation between channels was better than -30 dB. The (23) Na
      gradient echo images indicate a region where the field is strongly circularly
      polarized. The quadrature coil provided an SNR enhancement over a linear coil of
      1.4, in vitro and in vivo. CONCLUSION: It is feasible to construct a double
      quadrature (13) C-(1) H surface coil for proton decoupled sensitivity enhanced
      (13) C-NMR spectroscopy in humans at 7T.

PMID- 24590915
TI  - Protective effect of hydroalcoholic olive leaf extract on experimental model of
      colitis in rat: involvement of nitrergic and opioidergic systems.
AB  - The aim of the present study is to investigate the possible protective effect of
      dry olive leaf extract (OLE) against acetic acid-induced ulcerative colitis in
      rats, as well as the probable modulatory effect of nitrergic and opioidergic
      systems on this protective impact. Olive leaf extract was administered (250, 500
      and 750 mg/kg) orally for two successive days, starting from the colitis
      induction. To assess the involvement of nitrergic and opioidergic systems in the
      possible protective effect of OLE, L-NG-Nitroarginine Methyl Ester (10 mg/kg) and
      naltrexone (5 mg/kg) intraperitoneal (i.p.) were applied 30 min before
      administration of the extract for two successive days, respectively. Colonic
      status was investigated 48 h following induction through macroscopic,
      histological and biochemical analyses. Olive leaf extract dose-dependently
      attenuated acetic acid-provoked chronic intestinal inflammation. The extract
      significantly reduces the severity of the ulcerative lesions and ameliorated
      macroscopic and microscopic scores. These observations were accompanied by a
      significant reduction in the elevated amounts of TNF-alpha and interlukin-2
      markers. Moreover, both systems blockage reversed protective effects of OLE in
      the rat inflammatory bowel disease model. These finding demonstrated, for the
      first time, a possible role for nitrergic and opioidergic systems in the
      aforementioned protective effect, and the extract probably exerted its impact
      increasing nitric oxide and opioid tones.

PMID- 24590916
TI  - Advances in interferon-free hepatitis C therapy: 2014 and beyond.

PMID- 24590917
TI  - Porosity-controlled eggshell membrane as 3D SERS-active substrate.
AB  - We report on the fabrication of a surface-enhanced Raman scattering (SERS)
      platform, comprised of a three-dimensional (3D) porous eggshell membrane (ESM)
      scaffold decorated with Ag nanoparticles (NPs). Both native and treated ESM were
      used, where the treated ESM pore size and fiber crossing density was controlled
      by timed exposure to hydrogen peroxide (H2O2). Ag NPs were synthesized in situ by
      reduction of silver nitrate with ascorbic acid. Our results demonstrate that H2O2
      treated Ag-ESM provides a more densely packed 3D network of active material,
      which leads to consistently higher SERS enhancement than untreated Ag-ESM
      substrates.

PMID- 24590918
TI  - Tailored Panel Management: A Theory-Based Approach to Building and Maintaining
      Participant Commitment to a Longitudinal Study.
AB  - Many psychological processes unfold over time, necessitating longitudinal
      research designs. Longitudinal research poses a host of methodological
      challenges, foremost of which is participant attrition. Building on Dillman's
      work, we provide a review of how social influence and relationship research
      informs retention strategies in longitudinal studies. Objective: We introduce the
      tailored panel management (TPM) approach, which is designed to establish communal
      norms that increase commitment to a longitudinal study, and this commitment, in
      turn, increases response rates and buffers against attrition. Specifically, we
      discuss practices regarding compensation, communication, consistency, and
      credibility that increase longer term commitment to panel participation. Research
      design: Throughout the article, we describe how TPM is being used in a national
      longitudinal study of undergraduate minority science students. TheScienceStudy is
      a continuing panel, which has 12 waves of data collected across 6 academic years,
      with response rates ranging from 70% to 92%. Although more than 90% of
      participants have either left or graduated from their undergraduate degree
      program, this highly mobile group of people remains engaged in the study.
      TheScienceStudy has usable longitudinal data from 96% of the original panel.
      Conclusion: This article combines social psychological theory, current best
      practice, and a detailed case study to illustrate the TPM approach to
      longitudinal data collection. The approach provides guidance for other
      longitudinal researchers, and advocates for empirical research into longitudinal
      research methodologies.

PMID- 24590919
TI  - Systematic review of efficacy and safety of pemetrexed in non-small-cell-lung
      cancer.
AB  - INTRODUCTION: Lung cancer accounts for 20 % of cancer deaths in Spain. The most
      frequent subtype (87 %) is non-small cell lung cancer (NSCLC). Pemetrexed is a
      recently marketed drug added to NSCLC therapeutic arsenal. It seems to have
      become one of the most used options for the treatment of this condition over the
      last 3 years. AIM OF THE REVIEW: To evaluate the efficacy and safety of
      pemetrexed in NSCLC, in the different therapy lines. Method A systematic search
      of published literature was conducted using the main databases (MEDLINE, EMBASE,
      the Cochrane Library and the Center for Reviews and Dissemination) and
      subsequently a search of referenced literature was performed. We included
      clinical trials, meta-analyses and systematic reviews. The evaluation of the
      quality of the articles was performed by pairs using specific assessment scales,
      Critical Appraisal Skills Program (CASP) adapted for CASP Spain. Then we
      extracted data on efficacy and safety according to the treatment line assessed.
      RESULTS: We identified 277 references. Finally, nine clinical trials and a meta
      analysis complied with inclusion criteria. In first-line induction, treatment
      with pemetrexed associated with a platinum was similar in terms of efficacy to
      other alternative chemotherapy regimens, except in patients with non-squamous
      histology, in whom survival was higher in the experimental group. In maintenance
      treatment, greater efficacy was seen with pemetrexed in patients with non
      squamous histology. In second-line treatment, there were no significant
      differences in terms of efficacy and safety for pemetrexed treatment versus other
      chemotherapy options. The most frequent adverse reactions were: hematological,
      gastrointestinal and neurological. All were significantly less frequent with
      pemetrexed versus other alternative therapies, except for liver toxicity.
      CONCLUSIONS: Due to the high degree of uncertainty as to its efficacy in certain
      subgroups of patients, including conflicting data; to its recent incorporation,
      and therefore lack of safety data in the medium and long term, and the high
      budgetary impact of its incorporation into health systems, it seems reasonable to
      optimize its use, identifying those patients who may benefit most.

PMID- 24590920
TI  - Clinical pharmacist's role in implementing a smoking cessation intervention in a
      Swiss regional hospital: an exploratory study.
AB  - BACKGROUND: Smoking cessation represents one of the best means of preventing
      smoking-related complications. In recent years, a majority of hospitals have
      implemented smoke-free policies, making support for smoker patients a necessary
      and indispensable task. The clinical pharmacist is well-positioned to provide
      this kind of support, given a good understanding of the medical condition and
      pharmacotherapy of hospitalized patients and the possibility to acquire specific
      smoking cessation training. OBJECTIVES: This study aimed to evaluate the impact
      of a smoking cessation intervention for hospitalized patients by a clinical
      pharmacist previously trained for smoking cessation counselling. SETTING:
      Internal medicine department of a Swiss regional hospital. METHOD: Smoker
      patients hospitalized in this department were included in the study from mid
      September 2012 to mid-January 2013, according to the inclusion criteria. Moderate
      intensity smoking cessation interventions based on smoking counselling and
      motivational interviewing techniques were used, and a follow-up telephone call at
      least 1 month after discharge was made. Patients' pharmacotherapy was analysed
      with regards to interactions with tobacco smoke. MAIN OUTCOME MEASURES:
      Motivational stage, abstinence at follow-up, change of readiness to quit between
      hospital visit and follow-up, patients' evaluation of the programme,
      pharmacotherapy interventions. RESULTS: One hundred smoker patients were
      screened, of whom 41 received the intervention and 40 received a follow-up
      contact. At least 1 month after discharge, the readiness to quit of 53 % of
      patients improved and 33 % of patients declared themselves abstinent. Even though
      35 % of patients declared having mild to moderate withdrawal symptoms in
      hospital, only 15 % were interested in receiving nicotine replacement therapy.
      Study participants evaluated the intervention positively. CONCLUSION: A moderate
      intensity smoking cessation intervention in hospitalized patients was associated
      with a higher quit rate than in control groups from other studies, and their
      readiness to quit generally improved at least 1 month after hospital discharge. A
      clinical pharmacist trained for smoking cessation counselling can play a key role
      in providing such interventions, including the assessment of pharmacotherapy
      interactions with tobacco smoke.

PMID- 24590921
TI  - Divergence in skeletal mass and bone morphology in antarctic notothenioid fishes.
AB  - Although notothenioid fishes lack swim bladders, some species live temporarily or
      permanently in the water column. Given its relatively high density, skeletal mass
      is a key determinant of buoyancy. Notothenioids have reduced skeletal
      ossification, but there is little quantitative data on the phylogenetic
      distribution of this trait. We obtained dry skeletal masses for 54 specimens
      representing 20 species from six notothenioid families. Although comparative data
      are sparse, notothenioid skeletons comprise a smaller percentage of body mass,
      <3.5%, than those of three non-notothenioid perciforms. With relatively high
      skeletal mass, the non-Antarctic Bovichtus diacanthus is similar in skeletal mass
      to some non-notothenioids. Eleginops maclovinus, the non-Antarctic sister group
      of the Antarctic clade, has a relatively light skeleton (<2% of body mass)
      similar to many species in the Antarctic clade. Low skeletal mass is therefore a
      synapomorphy shared by Eleginops plus the Antarctic clade. We provide gross,
      histological, and micro-CT documentation of the structure and location of bone
      and cartilage in skulls, pectoral girdles, and vertebrae, with emphasis on the
      bovichtid B. diacanthus, the eleginopsid E. maclovinus, and the channichthyid
      Chaenodraco wilsoni. In Eleginops and the Antarctic clade, most bone is spongy
      and most species have persisting cartilage in the skull and appendicular
      skeleton. We also measured the relative size of the notochordal canal in adult
      vertebral centra of 38 species representing all eight families. There is
      considerable interspecific variation in this pedomorphic trait and all species
      show an ontogenetic reduction in the relative size of the canal. However, large
      persisting canals are present in adults of the Antarctic clade, especially in the
      nototheniids Pleuragramma and Aethotaxis and in a number of bathydraconid and
      channichthyid genera.

PMID- 24590922
TI  - Comparative studies of thermally induced homolytic carbon-carbon bond cleavage
      reactions of strained dicarba[2]ferrocenophanes and their ring-opened oligomers
      and polymers.
AB  - Reactivity studies of dicarba[2]ferrocenophanes and also their corresponding ring
      opened oligomers and polymers have been conducted in order to provide mechanistic
      insight into the processes that occur under the conditions of their thermal ring
      opening polymerisation (ROP) (300  degrees C). Thermolysis of
      dicarba[2]ferrocenophane rac-[Fe(eta(5)-C5H4)2(CHPh)2] (rac-14; 300  degrees C, 1
      h) does not lead to thermal ROP. To investigate this system further, rac-14 was
      heated in the presence of an excess of cyclopentadienyl anion, to mimic the
      postulated propagating sites for thermally polymerisable analogues. This afforded
      acyclic [(eta(5)-C5H5)Fe(eta(5)-C5H4)-CH2Ph] (17) through cleavage of both a Fe
      Cp bond and also the C-C bond derived from the dicarba bridge. Evidence
      supporting a potential homolytic C-C bond cleavage pathway that occurs in the
      absence of ring-strain was provided through thermolysis of an acyclic analogue of
      rac-14, namely [(eta(5)-C5H5)Fe(eta(5)-C5H4)(CHPh)2-C5H5] (15; 300  degrees C, 1
      h), which also afforded ferrocene derivative 17. This reactivity pathway appears
      general for post-ROP species bearing phenyl substituents on adjacent carbons, and
      consequently was also observed during the thermolysis of linear
      polyferrocenylethylene [Fe(eta(5)-C5H4)2(CHPh)2]n (16; 300  degrees C, 1 h),
      which was prepared by photocontrolled ROP of rac-14 at 5  degrees C. This
      afforded ferrocene derivative [Fe(eta(5)-C5H4CH2Ph)2] (23) through selective
      cleavage of the -H(Ph)C-C(Ph)H- bonds in the dicarba linkers. These processes
      appear to be facilitated by the presence of bulky, radical-stabilising phenyl
      substituents on each carbon of the linker, as demonstrated through the
      contrasting thermal properties of unsubstituted linear trimer [(eta(5)
      C5H5)Fe(eta(5)-C5H4)(CH2)2(eta(5)-C5H4)Fe(eta(5)-C5H4)(CH2)2(eta(5)
      C5H4)Fe(eta(5)-C5H5)] (29) with a -H2 C-CH2- spacer, which proved significantly
      more stable under analogous conditions. Evidence for the radical intermediates
      formed through C-C bond cleavage was detected through high-resolution mass
      spectrometric analysis of co-thermolysis reactions involving rac-14 and 15 (300 
      degrees C, 1 h), which indicated the presence of higher molecular weight species,
      postulated to be formed through cross-coupling of these intermediates.

PMID- 24590923
TI  - Role of angiotensin II and oxidative stress on renal aquaporins expression in
      hypernatremic rats.
AB  - The aim of this study was to assess whether endogenous Ang II and oxidative
      stress produced by acute hypertonic sodium overload may regulate the expression
      of aquaporin-1 (AQP-1) and aquaporin-2 (AQP-2) in the kidney. Groups of
      anesthetized male Sprague-Dawley rats were infused with isotonic saline solution
      (control) or with hypertonic saline solution (Na group, 1 M NaCl), either alone
      or with losartan (10 mg kg(-1)) or tempol (0.5 mg min(-1) kg(-1)) during 2 h.
      Renal function parameters were measured. Groups of unanesthetized animals were
      injected intraperitoneally with hypertonic saline solution, with or without free
      access to water intake, Na+W, and Na-W, respectively. The expression of AQP-1,
      AQP-2, Ang II, eNOS, and NF-kB were evaluated in the kidney by Western blot and
      immunohistochemistry. AQP-2 distribution was assessed by immunofluorescence. Na
      group showed increased natriuresis and diuresis, and Ang II and NF-kB expression,
      but decreased eNOS expression. Losartan or tempol enhanced further the diuresis,
      and AQP-2 and eNOS expression, as well as decreased Ang II and NF-kB expression.
      Confocal immunofluorescence imaging revealed labeling of AQP-2 in the apical
      plasma membrane with less labeling in the intracellular vesicles than the apical
      membrane in kidney medullary collecting duct principal cells both in C and Na
      groups. Importantly, our data also show that losartan and tempol induces a
      predominantly accumulation of AQP-2 in intracellular vesicles. In unanesthetized
      rats, Na+W group presented increased diuresis, natriuresis, and AQP-2 expression
      (112 +/- 25 vs 64 +/- 16; *p < 0.05). Water deprivation increased plasma sodium
      and diuresis but decreased AQP-2 (46 +/- 22 vs 112 +/- 25; Sp < 0.05) and eNOS
      expression in the kidney. This study is a novel demonstration that renal
      endogenous Ang II-oxidative stress, induced in vivo in hypernatremic rats by an
      acute sodium overload, regulates AQP-2 expression. 

PMID- 24590924
TI  - Ectopic expression of RBP4 impairs the insulin pathway and inguinal fat
      deposition in mice.
AB  - A large body of evidence has linked retinol-binding protein 4 (RBP4) to systemic
      insulin resistance, but little is known about its function in fat deposition.
      This study aimed to confirm the involvement of RBP4 in inguinal fat deposition
      and insulin by intraperitoneal injection of adenovirus-mediated RBP4 to mice.
      Intraperitoneal injection of adenoviral vectors was validated as an efficient
      gene manipulation tool for over-expressing recombinant proteins in vivo. Ectopic
      expression of RBP4 decelerated inguinal fat deposition by decreasing the size of
      adipocytes. Moreover, the introduction of exogenous RBP4 blunted the response of
      inguinal adipocytes to insulin signals. These findings suggest that RBP4 impaired
      in vivo adipogenesis, partly through the repression of the insulin pathway. 

PMID- 24590925
TI  - Evaluation of in vitro antioxidant, antimicrobial, genotoxic and anticancer
      activities of lichen Cetraria islandica.
AB  - In this study, the antioxidant, antimicrobial, genotoxic and anticancer
      activities of Cetraria islandica methanol extract were determined by using free
      radical and superoxide anion scavenging activity, reducing power, determination
      of total phenolic compounds and flavonoid contents, broth microdilution minimal
      inhibitory concentration against five bacterial and five fungal species,
      cytokinesis block micronucleus (MN) assay on peripheral blood lymphocytes (PBLs)
      and the microculture tetrazolium test on FemX (human melanoma) and LS174 (human
      colon carcinoma) cell lines. As a result of the study, we found that C. islandica
      methanol extract exhibited moderate free-radical-scavenging activity with IC50
      values 678.38 MUg/ml. Moreover, the tested extract had effective reducing power
      and superoxide anion radical scavenging. The minimal inhibitory concentration
      values against the tested microorganisms ranged from 0.312 to 5 mg/ml. The
      extract increased MN frequency in a dose dependent manner, but it was significant
      in higher tested concentrations (50, 100 and 200 MUg/ml). No significant
      differences were observed between NDI values in all treatments and untreated
      PBLs. In addition, the tested extract had strong anticancer activity towards both
      cell lines with IC50 values of 22.68 and 33.74 MUg/ml. It can be concluded that
      the tested extract exhibited a certain level of in vitro antioxidant,
      antimicrobial, genotoxic and anticancer activities. 

PMID- 24590927
TI  - The effects of lycopene on hepatic ischemia/reperfusion injury in rats.
AB  - There is a very little information about the protective effect of lycopene (LYC)
      against hepatic ischemia-reperfusion injury. The present study was designed to
      examine the possible protective effect of the strong antioxidant and anti
      inflammatory agent, LYC, on hepatic ischemia/reperfusion injury. For this
      purpose, rats were subjected to 45 min of hepatic ischemia followed by 60 min of
      reperfusion period. LYC at the doses of 2.5 and 5 mg/kg body weight (bw) were
      injected intraperitoneally, 60 min prior to ischemia. Upon sacrification, hepatic
      tissue samples were used for the measurement of catalase (CAT) activity and
      malondialdehyde (MDA) levels. Also, aspartate aminotransferase (AST), alanine
      aminotransferase (ALT) and lactate dehydrogenase (LDH) were assayed in serum
      samples. As a result of the use of LYC at the doses of 2.5 and 5 mg/kg bw; while
      improvements of the ALT, AST, LDH and MDA values were partial and dose-dependent,
      the improvement of CAT activity was total and dose-independent (p < 0.05). Our
      findings suggest that LYC has a protective effect against ischemia/reperfusion
      injury on the liver. 

PMID- 24590926
TI  - Genotoxic and oxidative damage potentials in human lymphocytes after exposure to
      terpinolene in vitro.
AB  - Terpinolene (TPO) is a monocyclic monoterpene found in the essential oils of
      various fir and pine species. Recent reports indicated that several monoterpenes
      could exhibit antioxidant effects in both human and animal experimental models.
      However, so far, the nature and/or biological roles of TPO have not been
      elucidated in human models yet. The aim of this study was to investigate the
      genetic, oxidative and cytotoxic effects of TPO in cultured human blood cells (n
      = 5) for the first time. Human blood cells were treated with TPO (0-200 mg/L) for
      24 and 48 h, and then cytotoxicity was detected by lactate dehydrogenase (LDH)
      release and [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] (MTT)
      assay, while DNA damage was also analyzed by micronucleus assay, sister chromatid
      exchanges assay and 8-oxo-2-deoxyguanosine (8-OH-dG) level. In addition,
      biochemical parameters [total antioxidant capacity (TAC) and total oxidative
      stress (TOS)] were examined to determine oxidative effects. The results of LDH
      and MTT assays showed that TPO (at concentrations greater than 100 mg/L)
      decreased cell viability. In our in vitro test systems, it was observed that TPO
      had no genotoxicity on human lymphocytes. Again, TPO (at 10, 25, 50 and 75 mg/L)
      treatment caused statistically important (p < 0.05) increases of TAC levels in
      human lymphocytes without changing TOS levels. In conclusion, TPO can be a new
      resource of therapeutics as recognized in this study with its non-genotoxic and
      antioxidant features. 

PMID- 24590928
TI  - The decreased secretion of hyaluronan by older human fibroblasts under
      physiological conditions is mainly associated with the down-regulated expression
      of hyaluronan synthases but not with the expression levels of hyaluronidases.
AB  - Although it has been reported that levels of hyaluronan are decreased in the
      dermis of aged skin, little is known about the cellular mechanism(s) underlying
      that hyaluronan deficiency. Since hyaluronan is produced by dermal fibroblasts
      and is secreted into the surrounding dermal tissues, we examined the secretion of
      hyaluronan by dermal fibroblasts and characterized its cellular mechanism using
      real-time RT-PCR and western blotting for its synthesizing and degrading enzymes,
      hyaluronan synthase and hyaluronidase, respectively. The secretion of hyaluronan
      by dermal fibroblasts derived from differently aged human donors, was higher in
      the younger human fibroblasts tested (0 and 19 years old) compared to the older
      human fibroblasts tested (39, 56 and 77 years old). The relative secretion levels
      of hyaluronan by the different human fibroblasts tested were attributable to the
      relative expression of hyaluronan synthases 1, 2, 3 but not hyaluronidases 1, 2
      enzymes at the gene and protein levels among those fibroblasts. These findings
      indicate that the deficiency of hyaluronan in the aged dermis might result from
      the down-regulation in the potential of older human fibroblasts to secrete
      hyaluronan and that decrease in secretory potential is mainly associated with the
      down-regulated expression of hyaluronan synthases, especially hyaluronan synthase
      2, but not with the expression levels of hyaluronidases. 

PMID- 24590929
TI  - Performance implications of chemical mobilization after microchannel IEF.
AB  - Chemical mobilization following IEF enables single-point detection of an ideally
      stationary equilibrium electrophoresis mode. Despite prior studies exploring
      optimization of chemical mobilization conditions and recent insight from
      numerical simulations, understanding of both chemical mobilization mechanisms and
      the implications of mobilization on IEF analytical performance remains limited.
      In this study, we utilize full-field imaging of microchannel IEF to assess the
      performance of a range of canonical chemical mobilization schemes. We empirically
      demonstrate and characterize key areas where limited understanding of performance
      implications exists, including: the effects of mobilization solution pH and ion
      concentration, differences between ionic and zwitterionic mobilization, and
      diffusion as a source of zone broadening. We utilize Simul5 simulations to gain
      insight into the sources of the measured performance differences. Measurements of
      the location, linearity, and slope of the IEF pH gradient (via fluorescent pH
      markers imaged before and during mobilization) as well as mobilization-associated
      broadening of focused analytes were performed to quantify performance and
      determine the dominant sources of variability. Our results suggest that
      nonuniform broadening of the pH gradient and changes in the pH gradient linearity
      stem from conductivity nonuniformities in the separation channel and not
      diffusion-associated band broadening during mobilization. 

PMID- 24590930
TI  - The ACA opens the door for two vulnerable populations.

PMID- 24590931
TI  - Living with HIV and growing old.
AB  - The rapid progress of antiretroviral therapy has meant that people living with
      HIV must face the trials of growing old. 

PMID- 24590933
TI  - Early HIV treatment led to life expectancy gains valued at $80 billion for people
      infected in 1996-2009.
AB  - In late 2009 US guidelines for HIV treatment were revised to recommend the
      initiation of combination antiretroviral therapy (cART) earlier in the course of
      the disease. We analyzed the life expectancy gains of people infected with HIV
      between the introduction of cART in 1996 and the 2009 guideline revisions.
      Compared to people who initiated cART late (defined as having a CD4 cell count of
      less than 350 per cubic millimeter of blood), those who initiated treatment early
      (with a CD4 count of 350-500) could expect to live 6.1 years longer, and the
      earliest initiators (with a CD4 count of more than 500) could expect an extra 9.0
      years of life. The total value of life expectancy gains to the early and earliest
      initiators of treatment was $80 billion, with each life-year valued at $150,000.
      The value of the survival gains was more than double the increase in drug
      manufacturers' revenues from early cART initiation. Our results clarify the
      economic implications of adherence to treatment guidelines.

PMID- 24590932
TI  - Early HIV treatment in the United States prevented nearly 13,500 infections per
      year during 1996-2009.
AB  - In recent years, guidelines for HIV treatment have recommended initiation of
      combination antiretroviral therapy (cART) earlier in the course of the disease
      than was previously the case. These recommendations stem in part from growing
      evidence that treatment reduces the risk of sexual transmission. We used an
      epidemiological model of disease transmission and progression to assess HIV
      prevention through early treatment-that is, initiation of cART when CD4 white
      blood cell counts are in excess of 350 cells per cubic millimeter. (CD4 cells are
      involved in the immune system's defense against tumors and infection; the number
      of CD4 cells in a cubic millimeter of blood is a standard measure of immune
      response to antiretroviral therapy.) We estimated that the actual timing of
      treatment initiation in the United States prevented 188,000 HIV cases in the
      period 1996-2009. "Very early" treatment (at CD4 counts greater than 500)
      accounted for four-fifths of the prevented cases. For all of the prevented cases,
      the losses in life expectancy that were avoided were worth $128 billion, assuming
      that a life-year has a value of $150,000. These findings underscore the cost
      effectiveness of early HIV treatment.

PMID- 24590934
TI  - The Affordable Care Act may increase the number of people getting tested for HIV
      by nearly 500,000 by 2017.
AB  - People are much less likely to engage in risky sexual behavior if they know that
      they are HIV-positive. Unfortunately, more than 18 percent of people living with
      HIV/AIDS in the United States are unaware of their HIV status, and about half of
      new HIV infections are transmitted from that "HIV unaware" population. For these
      reasons, HIV testing is at the forefront of HIV prevention strategies in the
      United States. The Affordable Care Act (ACA) may support these strategies, since
      gaining coverage increases the likelihood of being tested for HIV. We modeled the
      impact of the ACA on HIV testing, diagnoses, and awareness of being HIV-positive,
      assuming that only the eighteen states (and the District of Columbia) that had
      committed to expand Medicaid as of July 2013 did expand the program. We found
      that the ACA will result in an additional 466,153 people's being tested for HIV
      and 2,598 new diagnoses of HIV by 2017. Among people living with HIV/AIDS who
      gain insurance through the ACA, the share of the HIV unaware will decline by 22
      percent. The impact on both HIV testing and new diagnoses would be nearly 30
      percent larger if all fifty states expanded Medicaid. Policy makers should
      consider such epidemiological benefits when analyzing insurance expansion
      policies.

PMID- 24590935
TI  - Nearly 60,000 uninsured and low-income people with HIV/AIDS live in states that
      are not expanding Medicaid.
AB  - Health insurance gives people living with HIV/AIDS access to medical care,
      including antiretroviral therapy, which in turn can dramatically improve health
      and reduce the risk of HIV transmission. Yet many people living with HIV/AIDS
      remain uninsured. The Affordable Care Act (ACA) seeks to decrease the number of
      uninsured Americans in part by extending Medicaid coverage to individuals with
      incomes of up to 138 percent of the federal poverty level. However, many states
      are not moving forward with this expansion. Using national HIV surveillance data
      and data from the National Health Interview Survey, we estimated that nearly
      115,000 uninsured, low-income people living with HIV/AIDS would be eligible for
      Medicaid if all states adopted the expansion. Of these, nearly 60,000 live in
      states not moving forward with the Medicaid expansion. States' decisions about
      whether or not to participate in the expansion are likely to have important
      consequences for the health of this population and the evolution of the HIV
      epidemic.

PMID- 24590936
TI  - HIV care providers emphasize the importance of the Ryan White Program for access
      to and quality of care.
AB  - With the implementation of the Affordable Care Act (ACA) under way, some policy
      makers have questioned the continued relevance of the Ryan White HIV/AIDS Program
      as a safety net for people living with HIV/AIDS. We surveyed HIV care providers
      to understand the role of the Ryan White Program and to identify concerns
      regarding the ACA implementation. We also addressed whether the program is still
      relevant after ACA implementation and, if so, what elements should be retained.
      We found that providers consider the Ryan White Program to be critical in
      facilitating high-quality care for people living with HIV/AIDS. Most of the
      providers highlighted the program's support for providing medical and nonmedical
      case management as especially valuable and important to the entire continuum of
      care and for all patient subpopulations. Whether care is supplied by the Ryan
      White Program, Medicaid, or other means, our findings suggest that case
      management services will remain critical in treating HIV/AIDS as the health care
      landscape continues to evolve.

PMID- 24590937
TI  - Prevention and treatment produced large decreases in HIV incidence in a model of
      people who inject drugs.
AB  - In the United States, people who inject drugs continue to be at greatly increased
      risk of HIV infection. To estimate the effectiveness of various prevention
      scenarios, we modeled HIV transmission in a dynamic network of drug users and
      people who did not use drugs that was based on the New York Metropolitan
      Statistical Area population. We compared the projected HIV incidence in 2020 and
      2040 if current approaches continue to be used to the incidence if one or more of
      the following hypothetical interventions were applied: increased HIV testing,
      improved access to substance abuse treatment, increased use of needle and syringe
      programs, scaled-up treatment as prevention, and a "high impact" combination
      scenario, consisting of all of the strategies listed above. No strategy
      completely eliminated HIV transmission. The high-impact combination strategy
      produced the largest decrease in HIV incidence-a 62 percent reduction compared to
      the status quo. Our results suggest that increased resources for and investments
      in multiple HIV prevention approaches will be required to eliminate HIV
      transmission among people who inject drugs.

PMID- 24590938
TI  - Data-driven decision-making tools to improve public resource allocation for care
      and prevention of HIV/AIDS.
AB  - Public health agencies face difficult decisions when allocating scarce resources
      to control the spread of HIV/AIDS. Decisions are often made with few local
      empirical data. We demonstrated the use of the robust decision making approach in
      Los Angeles County, an approach that is data driven and allows decision makers to
      compare the performance of various intervention strategies across thousands of
      simulated future scenarios. We found that the prevailing strategy of emphasizing
      behavioral risk reduction interventions was unlikely to achieve the policy goals
      of the national HIV/AIDS strategy. Of the alternative strategies we examined,
      those that invested most heavily in interventions to initiate antiretroviral
      treatment and support treatment adherence were the most likely to achieve policy
      objectives. By employing similar methods, other public health agencies can
      identify robust strategies and invest in interventions more likely to achieve
      HIV/AIDS policy goals.

PMID- 24590939
TI  - HIV tests and new diagnoses declined after california budget cuts, but
      reallocating funds helped reduce impact.
AB  - Historically, California supplemented federal funding of HIV prevention and
      testing so that Californians with HIV could become aware of their infection and
      obtain lifesaving treatment. However, budget deficits in 2009 led the state to
      eliminate its supplemental funding for HIV prevention. We analyzed the impact of
      California's HIV resource allocation change between state fiscal years 2009 and
      2011. We found that the number of HIV tests declined 19 percent, from 66,629 to
      53,760, in local health jurisdictions with high HIV burden. In low-burden
      jurisdictions, the number of HIV tests declined 90 percent, from 20,302 to 2,116.
      New diagnoses fell from 2,434 in 2009 to 2,235 in 2011 (calendar years) in high
      burden jurisdictions and from 346 to 327 in low-burden ones. California's budget
      crunch prompted state and local programs to redirect remaining HIV funds from
      risk reduction education to testing activities. Thus, the impact of the budget
      cuts on HIV tests and new HIV diagnoses was smaller than might have been expected
      given the size of the cuts. As California's fiscal outlook improves, we recommend
      that the state restore supplemental funding for HIV prevention and testing.

PMID- 24590940
TI  - Mapping the HIV/AIDS epidemic.
AB  - One organization is using new mapping techniques to change how people see the
      impact of HIV on their communities. 

PMID- 24590941
TI  - The prospect of a generation free of HIV may be within reach if the right policy
      decisions are made.
AB  - Scientific advances have transformed HIV treatment and prevention, leading to the
      adoption of an approach that emphasizes broad testing and antiretroviral
      treatment at earlier stages in the disease, called "test and treat." In addition
      to clinical benefits, early treatment generates considerable social and economic
      value. These changes raise the prospect that for the first time since the 1980s,
      an entire generation might be free of HIV. However, achieving such a goal will
      require continued scientific advances and the presence of policies and programs
      to ensure that people living with HIV/AIDS have access to health care and adhere
      to treatment regimens. This article explores the opportunities and challenges
      that the Affordable Care Act (ACA) presents for people living with HIV/AIDS and
      discusses how the act's various components might interact with existing support
      for people with HIV/AIDS, such as the Ryan White Program. As the ACA's reforms
      proceed, coordinated state and federal programs must make smart policy choices so
      that critical access to and affordability of comprehensive care are maintained in
      the fight against HIV/AIDS.

PMID- 24590942
TI  - Survey finds that many prisons and jails have room to improve HIV testing and
      coordination of postrelease treatment.
AB  - Early diagnosis of HIV and effective antiretroviral treatment are key elements in
      efforts to reduce the morbidity and mortality associated with HIV. Incarcerated
      populations are disproportionately affected by HIV, with the disease's prevalence
      among inmates estimated to be three to five times higher than among the general
      population. Correctional institutions offer important opportunities to test for
      HIV and link infected people to postrelease treatment services. To examine HIV
      testing and policies that help HIV-positive people obtain treatment in the
      community after release, we administered a survey to the medical directors of the
      fifty state prison systems and of forty of the largest jails in the United
      States. We found that 19 percent of prison systems and 35 percent of jails
      provide opt-out HIV testing, which is recommended by the Centers for Disease
      Control and Prevention (CDC). Additionally, fewer than 20 percent of prisons and
      jails conform to the CDC's recommendations regarding discharge planning services
      for inmates transitioning to the community: making an appointment with a
      community health care provider, assisting with enrollment in an entitlement
      program, and providing a copy of the medical record and a supply of HIV
      medications. These findings suggest that opportunities for HIV diagnosis and
      linking HIV-positive inmates to community care after release are being missed in
      the majority of prison systems and jails.

PMID- 24590943
TI  - The critical link between health care and jails.
AB  - As a group, jail-involved individuals, which we define here as people with a
      history of arrest and jail admission in the recent past, carry a heavy illness
      burden, with high rates of infectious and chronic disease as well as mental
      illness and substance use. Because these people have tended to also be uninsured,
      jail frequently has been their only regular source of health care. Three thousand
      three hundred local and county jails processed 11.6 million admissions during the
      twelve-month period ending midyear 2012. The Urban Institute estimated as much as
      30 percent of some local corrections budgets is allocated to inmate health care
      services. This investment is largely lost when people are released back into the
      community, where they typically do not get treatment. For people with untreated
      substance use or mental illness, this issue reaches beyond public health, because
      without treatment, these people are at heightened risk of cycling into and out of
      jail for low-level, nonviolent offenses. This article offers eight policy
      recommendations to build a continuum of care that will ensure that jail-involved
      people get the care they need, regardless of where they reside. With the
      expansion of Medicaid eligibility under the Affordable Care Act, there is now a
      critical opportunity to bring the jail-involved population into the mainstream
      health care system, which benefits the health care and criminal justice systems
      and society at large.

PMID- 24590944
TI  - What the Affordable Care Act means for people with jail stays.
AB  - About one in six people expected to enroll in Medicaid under health reform
      expansions and nearly one in ten expected to enroll in qualified health plans
      through the health insurance Marketplaces will have spent some time in jail
      during the past year. People who have spent time in jail frequently cycle in and
      out of incarceration; have high rates of chronic physical, mental health, and
      substance use conditions; and historically have been uninsured and without access
      to continuous health care. The Affordable Care Act may not change the quality of
      health care in jails, but its provision of better access to care before and after
      people are incarcerated could have positive long-term effects on both the health
      of those individuals and overall health care costs. Achieving these results will
      require careful planning and coordination among jail health care programs,
      Medicaid, and Marketplace health plans. The use of electronic health records by
      jails and community providers could help ensure that treatments are consistent no
      matter where a patient resides. Policy makers and health plans could also ensure
      continuity of care by including in their networks some of the same safety-net
      providers that are under contract to furnish care to jail inmates.

PMID- 24590945
TI  - Medicaid expansion: considerations for states regarding newly eligible jail
      involved individuals.
AB  - The expansion of Medicaid eligibility to Americans with incomes up to 138 percent
      of the federal poverty level should greatly increase access to coverage and
      services for people recently released from jail and, thus, improve health
      outcomes and reduce recidivism in this population. The population is
      disproportionately male, minority, and poor; suffers from high rates of mental
      and substance abuse disorders; and is expected to make up a substantial portion
      of the Medicaid expansion population. To ensure connections to needed services
      after release from jail, states could help inmates determine their eligibility
      and enroll in Medicaid; take advantage of federal grants to automate systems that
      determine eligibility; and include a robust array of behavioral health services
      in Medicaid benefit packages. In most states, new partnerships between Medicaid
      and corrections agencies at both the state and local levels will be needed to
      support these activities.

PMID- 24590946
TI  - How health care reform can transform the health of criminal justice-involved
      individuals.
AB  - Provisions of the Affordable Care Act offer new opportunities to apply a public
      health and medical perspective to the complex relationship between involvement in
      the criminal justice system and the existence of fundamental health disparities.
      Incarceration can cause harm to individual and community health, but prisons and
      jails also hold enormous potential to play an active and beneficial role in the
      health care system and, ultimately, to improving health. Traditionally,
      incarcerated populations have been incorrectly viewed as isolated and self
      contained communities with only peripheral importance to the public health at
      large. This misconception has resulted in missed opportunities to positively
      affect the health of both the individuals and the imprisoned community as a whole
      and potentially to mitigate risk behaviors that may contribute to incarceration.
      Both community and correctional health care professionals can capitalize on these
      opportunities by working together to advocate for the health of the criminal
      justice-involved population and their communities. We present a set of
      recommendations for the improvement of both correctional health care, such as
      improving systems of external oversight and quality management, and access to
      community-based care, including establishing strategies for postrelease care and
      medical record transfers.

PMID- 24590947
TI  - Integrating correctional and community health care for formerly incarcerated
      people who are eligible for Medicaid.
AB  - Under the Affordable Care Act, up to thirteen million adults have the opportunity
      to obtain health insurance through an expansion of the Medicaid program. A great
      deal of effort is currently being devoted to eligibility verification, outreach,
      and enrollment. We look beyond these important first-phase challenges to consider
      what people who are transitioning back to the community after incarceration need
      to receive effective care. It will be possible to deliver cost-effective, high
      quality care to this population only if assistance is coordinated between the
      correctional facility and the community, and across diverse treatment and support
      organizations in the community. This article discusses several examples of
      successful coordination of care for formerly incarcerated people, such as Project
      Bridge and the Community Partnerships and Supportive Services for HIV-Infected
      People Leaving Jail (COMPASS) program in Rhode Island and the Transitions Clinic
      program that operates in ten US cities. To promote broader adoption of successful
      models, we offer four policy recommendations for overcoming barriers to
      integrating individuals into sustained, community-based care following their
      release from incarceration.

PMID- 24590948
TI  - Case studies from three states: breaking down silos between health care and
      criminal justice.
AB  - The jail-involved population-people with a history of arrest in the previous year
      has high rates of illness, which leads to high costs for society. A significant
      percentage of jail-involved people are estimated to become newly eligible for
      coverage through the Affordable Care Act's expansion of Medicaid, including
      coverage of substance abuse treatment and mental health care. In this article we
      explore the need to break down the current policy silos between health care and
      criminal justice, to benefit both sectors and reduce unnecessary costs resulting
      from lack of coordination. To draw attention to the hidden costs of the current
      system, we review three case studies, from Washington State, Los Angeles County
      in California, and New York City. Each case study addresses different aspects of
      care needed by or provided to the jail-involved population, including mental
      health and substance abuse, emergency care, and coordination of care transitions.
      Ultimately, bending the cost curve for health care and criminal justice will
      require greater integration of the two systems.

PMID- 24590949
TI  - Coverage expansion and the criminal justice-involved population: implications for
      plans and service connectivity.
AB  - People who have served time in US prisons and jails have high rates of
      undiagnosed chronic and infectious diseases, behavioral health conditions, and
      trauma. Because a large portion of this population are young men-a demographic
      previously underrepresented in Medicaid rolls-who have been uninsured, Medicaid
      payers and the managed care plans they contract with have little experience
      serving this population. To meet the Affordable Care Act's policy objectives of
      cost-efficient and effective care through improved and expanded access, health
      plans need to understand the epidemiology and care-seeking patterns of this
      population. Plans also need to develop outreach, communications, and engagement
      strategies and create service models designed to address these individuals'
      health care needs. Corrections departments and health plans should exchange
      information about the medical histories of people entering and leaving prisons
      and jails, promote models of peer support, and advocate for suspension rather
      than termination of Medicaid benefits during incarceration, so inmates can
      quickly regain coverage once they are released.

PMID- 24590950
TI  - The impact of policies promoting health information technology on health care
      delivery in jails and local communities.
AB  - The 1976 Supreme Court decision in Estelle v. Gamble declared that jails must
      provide medical treatment to detainees consistent with community standards of
      care. Yet despite their important role providing health care to about ten million
      people a year, jails remain largely siloed from the surrounding health care
      community, compromising inmates' health and adding to health care spending.
      Health information technology promises solutions. The current policy landscape,
      shaped by the Health Information Technology for Economic and Clinical Health
      (HITECH) Act and the Affordable Care Act, is favorable to jails' implementation
      of health information technology (IT). In this article we examine how decisions
      largely external to jails-coming from the Supreme Court, Congress, and local
      policy makers-have contributed to the growth of health IT within jails and health
      information exchange between jails and local communities. We also discuss privacy
      concerns under the Health Insurance Portability and Affordability Act and other
      legislation. This article highlights a rare confluence of events that could
      improve the health of an overlooked population.

PMID- 24590951
TI  - To improve public health and safety, one sheriff looks beyond the jail walls.

PMID- 24590952
TI  - HIV/AIDS: as the US crisis continues, funders respond.

PMID- 24590954
TI  - Malpractice reform and health reform.

PMID- 24590955
TI  - Malpractice reform: the authors reply.

PMID- 24590956
TI  - Slow growth in health care spending.

PMID- 24590957
TI  - From "There's Plenty of Room at the Bottom" to seeing what is actually there.

PMID- 24590959
TI  - Editorial.

PMID- 24590961
TI  - The effects of user fees on quality and utilization of primary health-care
      services in Afghanistan: a quasi-experimental health financing pilot study in a
      post-conflict setting.
AB  - BACKGROUND: After the fall of the Taliban regime, most clinics in Afghanistan
      were charging fees to patients. The government invested in monitoring and
      evaluation systems for its newly rebuilt primary care system, but little was
      known about the effects of user fees. This study was undertaken to provide
      evidence on user fees' effects on quality and service utilization and to help
      inform development of health financing policy and strategy. METHODS: A quasi
      experimental health financing pilot study was implemented in 2005. Forty-seven
      facilities were randomized to implement a standardized user fee intervention,
      offer free services, or serve as controls, continuing current cost-sharing
      systems. Revenues were co-managed by staff and community leaders for facility
      improvement. Baseline and follow-up facility assessments, exit interviews, and
      household surveys, as well as routine data were used to evaluate user fee effects
      over 2 years. RESULTS: Observed and perceived quality improved at most facilities
      but did not differ by study group. Utilization increased in all groups, but the
      increase was 682 to 748 visits per month larger in facilities randomized to free
      services compared with those randomized to fees or controls (p < 0.01).
      CONCLUSION: User fees demonstrated few beneficial effects and slowed the rate of
      increase of service utilization in Afghanistan. In 2008, the government abolished
      primary care fees, citing results of this study.

PMID- 24590962
TI  - Determining sucrose and glucose levels in dual-purpose sorghum stalks by Fourier
      transform near infrared (FT-NIR) spectroscopy.
AB  - BACKGROUND: Sorghum is an advanced biomass feedstock from which grain, sugar and
      stover can be used for biofuel production. Determinations of specific sugar
      contents in sorghum stalks help to make strategic decisions during plant
      breeding, processing, storage and optimization of fermentation conditions. In
      this study, Fourier transform near infrared (FT-NIR) spectroscopy was used as a
      relatively fast, low-cost, high-throughput assay to predict sucrose and glucose
      levels in stalks of 40 dwarf grain sorghum inbreds. RESULTS: The diffuse
      reflection spectra were pretreated with multiplicative scatter correction (MSC)
      and first-derivative Savitzy-Golay (SG-1). Calibrated models were developed by
      partial least squares regression (PLSR) analysis. Martens' uncertainty test was
      used to determine the most effective spectral region. The PLSR model for stalk
      sucrose content was built on 380 significant wavenumbers in the 4000-6999 cm(-1)
      range. The model was based on four factors and had RPD = 2.40, RMSEP = 1.77 and
      R(2) = 0.81. Similarly, the model for stalk glucose was built using 4000-9000 cm(
      1) and six factors, with RPD = 2.45, RMSEP = 0.73 and R(2) = 0.81. CONCLUSION:
      PLSR models were developed based on FT-NIR spectra coupled with multivariate data
      analysis to provide a quick and low-cost estimate of specific sugar contents in
      grain sorghum stalks. This sugar information helps decision making for sorghum
      based biomass processing and storage strategies.

PMID- 24590963
TI  - The development of tumor cell characteristics.
AB  - The origins of the characteristics associated with cells from both benign and
      malignant (cancer) tumors are proposed. It is shown that these deviant cells can
      originate as the result of the failure of the normal biochemical control of the
      formation of DNA and RNA. This change in characteristics is proposed as occurring
      in regions of metabolism where fluid movement is altered becoming restricted and
      giving rise to both physical and chemical changes in the associated cells.
      Treatment of cancerous cells based on the compounds with properties related to
      the cellular compounds involved in the control of nucleic acids is proposed.

PMID- 24590958
TI  - Sonic hedgehog-expressing basal cells are general post-mitotic precursors of
      functional taste receptor cells.
AB  - BACKGROUND: Taste buds contain ~60 elongate cells and several basal cells.
      Elongate cells comprise three functional taste cell types: I, glial cells; II,
      bitter/sweet/umami receptor cells; and III, sour detectors. Although taste cells
      are continuously renewed, lineage relationships among cell types are ill-defined.
      Basal cells have been proposed as taste bud stem cells, a subset of which express
      Sonic hedgehog (Shh). However, Shh+ basal cells turn over rapidly suggesting that
      Shh+ cells are post-mitotic precursors of some or all taste cell types. RESULTS:
      To fate map Shh-expressing cells, mice carrying ShhCreER(T2) and a high (CAG-CAT
      EGFP) or low (R26RLacZ) efficiency reporter allele were given tamoxifen to
      activate Cre in Shh+ cells. Using R26RLacZ, lineage-labeled cells occur singly
      within buds, supporting a post-mitotic state for Shh+ cells. Using either
      reporter, we show that Shh+ cells differentiate into all three taste cell types,
      in proportions reflecting cell type ratios in taste buds (I > II > III).
      CONCLUSIONS: Shh+ cells are not stem cells, but are post-mitotic, immediate
      precursors of taste cells. Shh+ cells differentiate into each of the three taste
      cell types, and the choice of a specific taste cell fate is regulated to maintain
      the proper ratio within buds.

PMID- 24590964
TI  - Stable genetic alterations of beta-catenin and ROR2 regulate the Wnt pathway,
      affect the fate of MSCs.
AB  - The Wnt pathways have been shown to be critical for the fate of mesenchymal stem
      cells (MSCs) in vitro, but their roles in MSCs in vivo remain poorly
      characterized due to the lack of stable alterations in their signaling. In the
      present study, we constructed long-term and stable mMSCs lines with activated and
      inactivated beta-catenin (the key molecule of the canonical Wnt signaling
      pathway) or ROR2 (the key molecule of the noncanonical Wnt5a/ROR2 signaling
      pathway) modifications with lentiviral vectors. We found that the transduction
      efficiencies mediated by the lentiviral vectors were 92.61-97.04% and were
      maintained over 20 passages of mMSCs. Transfection by lentiviral vectors not only
      regulated the mRNA and protein expression of beta-catenin or ROR2 but also
      regulated nuclear beta-catenin accumulation or the Wnt5a/JNK and Wnt5a/PKC
      pathways belonging to the canonical Wnt and noncanonical Wnt5a/ROR2 pathways,
      respectively. beta-Catenin or ROR2 gene overexpression promoted mMSC
      proliferation, migration and differentiation into osteoblasts, while inhibiting
      the adipogenic differentiation of mMSCs. In contrast, inactivation of the beta
      catenin or ROR2 genes resulted in the opposite effects. Therefore, these results
      confirm that lentiviral vector transduction can facilitate sustained and
      efficient gene modification of the Wnt pathway in mMSCs. This study provides a
      method to investigate the effects of the Wnt pathway on the fate of mMSCs in vivo
      and for the further improvement of MSC-based therapies.

PMID- 24590965
TI  - Ivabradine protects against ventricular arrhythmias in acute myocardial
      infarction in the rat.
AB  - Ventricular arrhythmias are an important cause of mortality in the acute
      myocardial infarction (MI). To elucidate effect of ivabradine, pure heart rate
      (HR) reducing drug, on ventricular arrhythmias within 24 h after non-reperfused
      MI in the rat. ECG was recorded for 24 h after MI in untreated and ivabradine
      treated rats and episodes of ventricular tachycardia/fibrillation (VT/VF) were
      identified. Forty-five minutes and twenty-four hours after MI epicardial
      monophasic action potentials (MAPs) were recorded, cardiomyocyte Ca(2+) handling
      was assessed and expression and function of ion channels were studied. Ivabradine
      reduced average HR by 17%. Combined VT/VF incidence and arrhythmic mortality were
      higher in MI versus MI + Ivabradine rats. MI resulted in (1) increase of Ca(2+)
      sensitivity of ryanodine receptors 24 h after MI; (2) increase of HCN4 expression
      in the left ventricle (LV) and funny current (IF) in LV cardiomyocytes 24 h after
      MI, and (3) dispersion of MAP duration both 45 min and 24 h after MI. Ivabradine
      partially prevented all these three potential proarrhythmic effects of MI.
      Ivabradine is antiarrhythmic in the acute MI in the rat. Potential mechanisms
      include prevention of: diastolic Ca(2+)-leak from sarcoplasmic reticulum,
      upregulation of IF current in LV and dispersion of cardiac repolarization.
      Ivabradine could be an attractive antiarrhythmic agent in the setting of acute
      MI.

PMID- 24590970
TI  - The Research Domain Criteria: moving the goalposts to change the game.
AB  - There is increasing concern that a reliance on the descriptive, syndrome-based
      diagnostic criteria of ICD and DSM is impeding progress in research. The USA's
      major funder of psychiatric research, the National Institute of Mental Health
      (NIMH), have stated their intention to encourage more research across diagnostic
      categories using a novel framework based on findings in neuroscience. 

PMID- 24590971
TI  - An end to psychiatric detention? Implications of the United Nations Convention on
      the Rights of Persons with Disabilities.
AB  - The United Nations Convention on the Rights of Persons with Disabilities is a
      welcome articulation of the rights of the disabled. However, as its definition of
      disability appears to include mental illness, the UK appears to violate it by
      linking mental illness with detention. Clarity and, possibly, change are needed. 

PMID- 24590972
TI  - Meeting the mental health needs of refugees and asylum seekers.
AB  - Mental health provision for diverse refugee populations is faced with a number of
      challenges, and requires the development and evaluation of flexible service
      models that maximise capacity and utilise existing non-specialist resources.
      Emerging therapeutic approaches should be applied in real settings, adapted to
      cultural needs and integrated with the other agencies involved. 

PMID- 24590973
TI  - What is it like to be diagnosed with bipolar illness, borderline personality
      disorder or another diagnosis with mood instability?
AB  - Patients with mood instability represent a significant proportion of patients
      with mental illness. Important lessons need to be learnt about how current
      assessment processes do not meet their expectations. Changes at various levels,
      including medical and nursing education, service provision and research
      priorities, appear necessary if we are to help our patients better. 

PMID- 24590974
TI  - Rates of violence in patients classified as high risk by structured risk
      assessment instruments.
AB  - BACKGROUND: Rates of violence in persons identified as high risk by structured
      risk assessment instruments (SRAIs) are uncertain and frequently unreported by
      validation studies. AIMS: To analyse the variation in rates of violence in
      individuals identified as high risk by SRAIs. METHOD: A systematic search of
      databases (1995-2011) was conducted for studies on nine widely used assessment
      tools. Where violence rates in high-risk groups were not published, these were
      requested from study authors. Rate information was extracted, and binomial
      logistic regression was used to study heterogeneity. RESULTS: Information was
      collected on 13 045 participants in 57 samples from 47 independent studies.
      Annualised rates of violence in individuals classified as high risk varied both
      across and within instruments. Rates were elevated when population rates of
      violence were higher, when a structured professional judgement instrument was
      used and when there was a lower proportion of men in a study. CONCLUSIONS: After
      controlling for time at risk, the rate of violence in individuals classified as
      high risk by SRAIs shows substantial variation. In the absence of information on
      local base rates, assigning predetermined probabilities to future violence risk
      on the basis of a structured risk assessment is not supported by the current
      evidence base. This underscores the need for caution when such risk estimates are
      used to influence decisions related to individual liberty and public safety.

PMID- 24590975
TI  - Predicting violent offences by released prisoners.

PMID- 24590976
TI  - Authors' reply.

PMID- 24590977
TI  - Effectiveness of methadone treatment for heroin addiction.

PMID- 24590978
TI  - Authors' reply.

PMID- 24590979
TI  - Psychosis as a failure of reality testing.

PMID- 24590980
TI  - Authors' reply.

PMID- 24590981
TI  - Psychotherapy for severe somatoform disorder: problems with missing studies.

PMID- 24590982
TI  - Authors' reply.

PMID- 24590984
TI  - Fibroblast growth factor 21 protects against acetaminophen-induced hepatotoxicity
      by potentiating peroxisome proliferator-activated receptor coactivator protein
      1alpha-mediated antioxidant capacity in mice.
AB  - Acetaminophen (APAP) overdose is a leading cause of drug-induced hepatotoxicity
      and acute liver failure worldwide, but its pathophysiology remains incompletely
      understood. Fibroblast growth factor 21 (FGF21) is a hepatocyte-secreted hormone
      with pleiotropic effects on glucose and lipid metabolism. This study aimed to
      investigate the pathophysiological role of FGF21 in APAP-induced hepatotoxicity
      in mice. In response to APAP overdose, both hepatic expression and circulating
      levels of FGF21 in mice were dramatically increased as early as 3 hours, prior to
      elevations of the liver injury markers alanine aminotransferase (ALT) and
      aspartate aminotransferase (AST). APAP overdose-induced liver damage and
      mortality in FGF21 knockout (KO) mice were markedly aggravated, which was
      accompanied by increased oxidative stress and impaired antioxidant capacities as
      compared to wild-type (WT) littermates. By contrast, replenishment of recombinant
      FGF21 largely reversed APAP-induced hepatic oxidative stress and liver injury in
      FGF21 KO mice. Mechanistically, FGF21 induced hepatic expression of peroxisome
      proliferator-activated receptor coactivator protein-1alpha (PGC-1alpha), thereby
      increasing the nuclear abundance of nuclear factor erythroid 2-related factor 2
      (Nrf2) and subsequent up-regulation of several antioxidant genes. The beneficial
      effects of recombinant FGF21 on up-regulation of Nrf2 and antioxidant genes and
      alleviation of APAP-induced oxidative stress and liver injury were largely
      abolished by adenovirus-mediated knockdown of hepatic PGC-1alpha expression,
      whereas overexpression of PGC-1alpha was sufficient to counteract the increased
      susceptibility of FGF21 KO mice to APAP-induced hepatotoxicity. CONCLUSION: The
      marked elevation of FGF21 by APAP overdose may represent a compensatory mechanism
      to protect against the drug-induced hepatotoxicity, by enhancing PGC-1alpha/Nrf2
      mediated antioxidant capacity in the liver.

PMID- 24590985
TI  - Lateral magnetic near-field imaging of plasmonic nanoantennas with increasing
      complexity.
AB  - The design of many promising, newly emerging classes of photonic metamaterials
      and subwavelength confinement structures requires detailed knowledge and
      understanding of the electromagnetic near-field interactions between their
      building blocks. While the electric field distributions and, respectively, the
      electric interactions of different nanostructures can be routinely measured, for
      example, by scattering near-field microscopy, only recently experimental methods
      for imaging the magnetic field distributions became available. In this paper, we
      provide direct experimental maps of the lateral magnetic near-field distributions
      of variously shaped plasmonic nanoantennas by using hollow-pyramid aperture
      scanning near-field optical microscopy (SNOM). We study both simple plasmonic
      nanoresonators, such as bars, disks, rings and more complex antennas. For the
      studied structures, the magnetic near-field distributions of the complex
      resonators have been found to be a superposition of the magnetic near-fields of
      the individual constituting elements. These experimental results, explained and
      validated by numerical simulations, open new possibilities for engineering and
      characterization of complex plasmonic antennas with increased functionality. 

PMID- 24590986
TI  - Injury to ulnar collateral ligament of thumb.
AB  - Injury of the ulnar collateral ligament (UCL) of thumb can be incapacitating if
      untreated or not treated properly. This injury is notorious for frequently being
      missed by inexperienced health care personnel in emergency departments. It has
      frequently been described in skiers, but also occurs in other sports such as
      rugby, soccer, handball, basketball, volleyball and even after a handshake. The
      UCL of the thumb acts as a primary restraint to valgus stress and is injured if
      hyperabduction and hyperextension forces are applied to the first
      metacarpophalangeal joint. The diagnosis is best established clinically, though
      MRI is the imaging modality of choice. Many treatment options exist, surgical
      treatment being offered depending on various factors, including timing of
      presentation (acute or chronic), grade (severity of injury), displacement (Stener
      lesion), location of tear (mid-substance or peripheral), associated or
      concomitant surrounding tissue injury (bone, volar plate, etc.), and patient
      related factors (occupational demands, etc.). This review aims to identify the
      optimal diagnostic techniques and management options for UCL injury available
      thus far. 

PMID- 24590987
TI  - Transcription factor Runx2 in the low bone mineral density of girls with
      adolescent idiopathic scoliosis.
AB  - OBJECTIVE: The molecular mechanism of low bone mass in girls with adolescent
      idiopathic scoliosis (AIS) has not been ascertained. Runx2 is a critical
      transcription factor regulating osteoblast differentiation and maturation. The
      present study aimed to explore the possible relationship between Runx2 expression
      in osteoblasts and bone mineral density (BMD) in subjects with AIS. METHODS:
      Twenty-two girls with AIS scheduled to corrective surgery with iliac crest as
      donor site of autograft for spinal fusion were recruited. The BMD of lumbar spine
      and femoral neck were assessed by dual-energy X-ray absorptiometry, then patients
      were divided into two groups with either normal or reduced BMD. Cancellous bone
      was harvested from their iliac crests for primary culture of osteoblasts. mRNA
      and protein expression of Runx2 were assayed by reverse transcription-polymerase
      chain reaction and western blotting, respectively. Results were compared between
      the two groups and correlated with BMD. RESULTS: AIS patients with normal BMD
      showed comparable maturity and body mass index but significant lower Cobb angle
      of main curve than those of patients with reduced BMD. The mean BMD of lumbar
      spine and femoral neck were 0.993 g/m(2) and 0.911 g/m(2) in patients with normal
      BMD, and were 0.757 g/m(2) and 0.733 g/m(2) in those with reduced BMD,
      respectively. The differences were significant between two groups (P < 0.05). The
      relative mean mRNA and protein expression of Runx2 were 0.49 +/- 0.12 and 0.062
      +/- 0.020 in AIS with normal BMD, 0.35 +/- 0.12 and 0.042 +/- 0.006 in AIS with
      reduced BMD, respectively. Significantly lower Runx2 mRNA and protein expression
      were found in patients with AIS patients with reduced BMD than in those with
      normal BMD (P < 0.05). After controlling for age, weight and body mass index,
      positive correlations were found between Runx2 expression of both mRNA and
      protein and BMD of lumbar spine and femoral neck. CONCLUSION: The abnormal
      expression of Runx2 in patients with AIS and reduced BMD indicates abnormal
      regulation of differentiation of their osteoblasts. Runx2 may play an important
      role in the pathogenesis of reduced BMD in patients with AIS.

PMID- 24590988
TI  - Does spinal alignment influence acetabular orientation: a study of spinopelvic
      variables and sagittal acetabular version.
AB  - OBJECTIVE: Although hip alignment and spinal alignment have been studied
      individually, there is little information concerning the relationship between
      them. The questions addressed in this study are: (i) Is there a reproducible
      measure of sagittal plane acetabular orientation; (ii) Is sagittal plane
      acetabular orientation determined more by pelvic incidence (PI) or acetabular
      wall coverage? METHODS: Data on patients who had undergone screening by CT scan
      of the pelvis for non-orthopedic indications from 2005-2010 were retrospectively
      studied. There were 164 patients of mean age 59 years (range, 27-87). Patients
      with pelvic trauma, hip arthroplasty or other hip pathology were excluded.
      Measurements of relevant acetabular and spinopelvic variables were made in the
      sagittal plane. The sacro-acetabular angle (SA) was defined as the angle between
      a tangent line to the anterior and posterior walls of the acetabulum and the S1
      endplate. Multiple regression analysis was used to determine which factors
      contribute to SA angle. RESULTS: The mean sacro-acetabular angle was 72 degrees 
      (SD = 14.8 degrees ). Center edge angles (CEAs) were measured at the anterior and
      posterior walls of the acetabulum. Mean anterior CEA was 69 degrees  (SD = 8.3
      degrees ) and posterior CEA 107 degrees  (SD = 16.4 degrees ). Regression
      analysis revealed the largest significant predictors of SA angle were PI and A
      CEA. CONCLUSIONS: Sagittal acetabular orientation is related to spino-pelvic
      balance and morphological characteristics. Increased PI or posterior wall
      coverage corresponds to a more vertical acetabular orientation. Sagittal plane
      acetabular alignment may be an important variable in achieving favorable results
      after reconstruction.

PMID- 24590989
TI  - Metabolic syndrome increases the prevalence of spine osteoarthritis.
AB  - OBJECTIVE: To determine whether the prevalence of severe spinal osteoarthritis
      (OA) increases with the number of metabolic syndrome (MetS) risk factors.
      METHODS: Data from a single surgeon's high volume, spine surgery practice were
      reviewed. Severe OA was defined as degenerative spondylolisthesis or cervical or
      lumbar stenosis causing neurologically based symptoms and early OA as lumbar and
      cervical spondylosis causing axial pain only. Logistic regression modeling was
      used to determine the odds (adjusted for age and sex) of having severe spine OA
      with more numerous MetS risk factors. RESULTS: Severe spinal OA was identified in
      839/1502 patients (55.9%) and early OA in the remaining 663 individuals (44.1%).
      The overall prevalence of MetS was 30/1502 (2.0%): 26/839 (3.1%) in the severe OA
      group and 4/663 (0.6%) in the early OA group (P = 0.001). Presence of all four
      MetS risk factors was associated with almost quadruple the odds of having severe
      OA as compared with absence of risk factors (OR 3.9 [1.4-11.6], P < 0.01).
      CONCLUSION: The components of MetS are more prevalent in subjects with severe
      spinal OA than in those with spondylosis causing axial pain. Future study of the
      association between MetS and the incidence of OA is required.

PMID- 24590990
TI  - Comparison between drainage and non-drainage after total hip arthroplasty in
      Chinese subjects.
AB  - OBJECTIVE: To assess the difference between drainage and non-drainage after total
      hip arthroplasty (THA) in Chinese subjects by evaluating post-operative
      complications and joint function. METHODS: One hundred and sixty-eight patients
      undergoing THA were randomly allocated into drainage (83 patients) and non
      drainage groups (85 patients). All surgeries were performed by one surgical team
      using the same pre-, intra-, and postoperative techniques. Measured items
      included: hemoglobin (Hb), superficial and deep wound infection, volume of blood
      transfusion, wound hematoma thickness, range of motion (ROM) of the hip, wound
      healing time, ecchymosis and tension vesicles around the wound. RESULTS: Early
      after THA, the Hb decreased significantly in the drainage group. There was no
      significant difference between non-drainage and drainage groups in need for or
      volume of blood transfusions (9.6% vs 8.2%, P = 0.100; 3.8 units vs 2.9 units, P
      = 0.089, respectively). In the non-drainage group, the incidence of superficial
      infection, ecchymosis and tension vesicles was significantly higher than in the
      drainage group (10.6% vs 2.4%, P = 0.031; 12.9% vs 3.6%, P = 0.026; 16.5% vs
      4.8%, P = 0.013, respectively). In addition, the non-drainage group had a greater
      volume of hematomas (P = 0.000). Patients in the non-drainage group had smaller
      ROMs early after surgery but the final ROMs did not differ significantly between
      groups. No deep infection occurred in either group. CONCLUSION: Non-drainage may
      reduce postoperative blood loss but has no benefits regarding blood transfusion
      or deep infection. It may cause more post-operative complications because of
      restriction of early postoperative exercise by pain and swelling. Therefore we
      suggest routine use of drainage after THA.

PMID- 24590991
TI  - Total knee arthroplasty in Asian subjects: preoperative range of motion
      determines postoperative range of motion?
AB  - OBJECTIVE: To evaluate whether preoperative range of motion is a key determinant
      of postoperative range of motion in Asian patients undergoing conventional total
      knee arthroplasty. METHODS: A retrospective review of 302 patients who underwent
      primary total knee arthroplasty performed by a single surgeon was conducted.
      Patients who had a fixed flexion deformity of >=15 degrees  were excluded.
      Postoperative range of motion (ROM) was measured prospectively. Patients were
      stratified into two groups: preoperative ROM < 110 degrees  and preoperative ROM
      >= 110 degrees . Postoperative ROM and mean change in ROM at 6 months and 2 years
      of follow-up were then compared using Student's t-test. RESULTS: Group of ROM <
      110 degrees  had a poorer postoperative range of motion at both 6-months and 2
      years of follow-up than Group of ROM >= 110 degrees  (P < 0.001).
      Postoperatively, Group of ROM < 110 degrees  had gained range of motion whereas
      Group of ROM >= 110 degrees  had lost range of motion (P < 0.001). CONCLUSIONS:
      Similar to the Western population, preoperative range of motion is a key
      determinant of postoperative range of motion in Asian patients. This should be
      taken into consideration by surgeons during preoperative planning and in managing
      patients' expectations.

PMID- 24590992
TI  - Lateral patellar translation effects after arthroscopic partial meniscectomy of
      torn discoid lateral meniscus.
AB  - OBJECTIVE: To investigate the effects of arthroscopic partial meniscectomy of
      torn discoid lateral meniscus on patellar tracking. METHODS: In all, 112 patients
      (112 knees) who underwent arthroscopic partial meniscectomy participated in the
      study. All subjects were examined with standing weight-bearing magnetic resonance
      imaging (MRI) preoperatively and one month postoperation. Axial-plane images
      through the maximum width of the patella and the maximum dorsal area of the
      femoral condyles were superimposed and the bisect offset index used to quantify
      patellar translation. Differences between pre- and postoperation in the bisect
      offset indexes were calculated and compared by Student's paired t-test. P < 0.05
      was considered statistically significant. RESULTS: Before surgery, the mean
      bisect offset index was 0.574 (0.437-0.692). One month postoperation, the mean
      bisect offset index was 0.622 (0.510-0.801). The postoperation bisect offset
      index increased by an average of 0.048 (-0.018 to 0.129) compared with the
      preoperation value; this difference is statistically significant result (t =
      18.33, P < 0.01). CONCLUSION: After arthroscopic partial meniscectomy, the
      patella translates more lateral to the femoral trochlear groove. These results
      suggest that arthroscopic partial meniscectomy may result in patellar
      maltracking.

PMID- 24590993
TI  - Perforator pedicled propeller flaps for soft tissue coverage of lower leg and
      foot defects.
AB  - OBJECTIVE: To investigate the efficiency of perforator pedicled propeller flaps
      for soft tissue coverage of lower leg and foot defects. METHODS: Twenty patients
      (12 male, 8 females; mean age 28 years, range, 5-75) with soft tissue defects of
      the lower leg and foot were retrospectively reviewed. Their defects had been
      repaired with perforator pedicled propeller flaps from September 2011 to October
      2013 and included five cases of injuries caused by spokes, four of infection with
      postoperative skin necrosis, two of dorsal skin defects caused by heavy objects
      and nine caused by car accidents. The areas of soft tissue defect were from 2 cm
      * 8 cm to 10 cm * 20 cm. Fifteen cases had terminal branch of the peroneal artery
      perforator flaps and five posterior tibia artery perforator flaps, flap size
      ranging from 5 cm * 11 cm to 12 cm * 28 cm. Color Doppler ultrasound was used to
      locate all perforator vessels, the calibers of which ranged from 0.8 mm to 1.0
      mm. RESULTS: The intraoperative coincidence rate of the color Doppler ultrasound
      was 96.7%. The donor sites were sutured directly in 12 cases and skin grafted in
      8. One case had a venous crisis within 24 h that was treated by removal some
      sutures and drainage. All cases were followed up for 1-18 months; all flaps
      survived well and pedicles had a satisfactory appearance. The patients were
      extremely satisfied with the results for repair. CONCLUSION: Perforator pedicled
      propeller flaps have the advantages over other pedicle flap of being simple,
      safe, and effective and not involving vascular anastomosis.

PMID- 24590995
TI  - The "TFP" fusion technique for posterior 360 degrees  lumbar fusion: a
      combination of open decompression, transforaminal lumbar interbody fusion, and
      facet fusion with percutaneous pedicle screw fixation.
AB  - Because degenerative spondylolithesis is prevalent in the elderly with associated
      osteoporosis, the rate of failure of pedicle screws is high; this leads to
      pseudoarthrosis and potentially requires reoperation. The burden of recurrent
      symptoms and reoperation is sufficiently significant to warrant prevention. We
      here describe a hybrid technique that involves a combination of a unilateral
      approach to bilateral decompression via a midline incision, transforaminal lumbar
      interbody fusion (TLIF), contralateral facet fusion, and percutaneously placed
      pedicle screws without compromising operative time and visualization. This
      approach is familiar to spine surgeons, adheres to the basic principles of
      minimally invasive spine surgery technique, minimizes dural and neural injury
      because of the unilateral TLIF approach, and provides a superior fusion construct
      because of facet fusion. In this procedure, patients with degenerative
      spondylolisthesis or scoliosis with moderate-severe canal/foraminal stenosis
      undergo a midline unilateral TLIF and contralateral facet fusion with closure of
      the midline incision. Percutaneous pedicle screws are inserted under stereotactic
      guidance with reduction of the deformity using a pedicle screws construct. Rods
      are inserted percutaneously to link the pedicle screws. Image intensification is
      used to confirmed satisfactory screw placement and reduction of the
      spondylolisthesis. 

PMID- 24590994
TI  - New cage for posterior minimally invasive lumbar interbody fusion: a study in
      vitro and in vivo.
AB  - OBJECTIVE: To design a new type of interbody fusion device made of nickel
      titanium NiTi shape memory alloy and to compare segmental stiffness after various
      posterior lumbar interbody fusion (PLIF) procedures in vitro and in vivo.
      METHODS: Twelve sheep lumbar functional spinal units were randomly allocated to
      four groups. One acted as controls (N); the other three were treated with
      autogenous iliac crest bone dowel graft (L), a threaded cylindrical titanium (KC)
      interbody fusion device (TFC) or a new type of interbody fusion device made of
      NiTi shape memory alloy (NT) containing autogenous iliac crest graft. In
      addition, 15 sheep were allocated to three groups; one served as controls and the
      other two underwent TFC (KC) or NiTi-FC (NT). Nondestructive mechanical tests
      were performed in pure compression, extension, lateral bending and torsion. The
      operated spines were photographed regularly to assess changes in interbody height
      and degree of fusion. The animals were killed at 6 months for histologic testing.
      RESULTS: Biomechanical tests showed both the strength and axial stiffness of the
      NT and KC groups were significantly higher than those of the control group and L
      group (P < 0.05). When the mechanical performance in torque and torsion of each
      group were compared, the same results could be obtained. The maximal destructive
      load of the NiTi-TFC was 11 200 N and the safety coefficient was above 1.2.
      Radiological observations revealed that the bone callus around the interbody
      fusion device were gradually increased postoperatively (2 months, no obvious; 4
      months, poorly define; 6 months, dense). The KC and NT group had lost 16% and
      16.5% of their postoperative height but remained well above normal disc height (P
      < 0.05). Histologic examination showed new trabeculation connected with that of
      the host. CONCLUSION: The mechanical characteristics of the NiTi-TFC are
      excellent and it is safe and reliable.

PMID- 24590996
TI  - A "two-incision" approach for en bloc resection of periacetabular tumors with
      illustrations from a cadaver.
AB  - A "two-incision" approach for en bloc resection of periacetabular tumors and
      prosthesis reconstruction is described. The first incision begins in the middle
      of the iliac crest, continues over the inguinal ligament, extends to the
      symphysis pubis and then turns down to ischial tuberosity. The muscles attached
      to the iliac crest are only separated from its internal side. All the attachments
      of the abductor muscles to the iliac crest are left intact. The second incision
      runs from the sacroiliac joint to the greater trochanter and is curved in shape,
      providing external exposure of the sciatic notch and ischial tuberosity.
      Communication between the two approaches is possible inside and outside under the
      abductor muscles or through the sciatic notch. En bloc resection of the tumor is
      performed by cutting the pubic symphysis and iliac as planned preoperatively. The
      iliac osteotomy is performed by using a Gigli saw that has been led through the
      sciatic notch and under the abductor muscles. This "two-incision" approach not
      only provides enough exposure to perform en bloc resection of periacetabular
      tumors, but also protects the continuity of the abductor muscles between the
      pelvis and greater trochanter, thus preventing prosthesis dislocation. 

PMID- 24590997
TI  - Resection of inferior pubic ramus tumors through a femoribus internus-perineal
      approach.
AB  - An operative approach to the inferior pubic ramus that was utilized in four
      patients with various bone tumors in the inferior pubic ramus is described here.
      These patients were successfully managed though a femoribus internus (inner
      thigh)-perineal approach. Data concerning preoperative and postoperative
      symptoms, surgical procedures, and outcomes are presented. There was no
      recurrence in the four cases and the pain associated with an initial pelvic floor
      had completely resolved except one case. The slight limitation in range of motion
      of the left hip joint and pain were performed in the same case postoperatively.
      The Musculoskeletal Tumor Society scores were 28, 15, 25, and 18 at the final
      follow-up. A typical case is described in full and our experience concerning
      surgical indications, and intraoperative issues in tumor patients discussed. The
      purpose of this paper is to recommend that the femoribus internus-perineal
      approach be used to resect the inferior pubic ramus, whether affected by
      osteomyelitis, bone tumor, or tuberculosis, but especially in patients with
      tumors. 

PMID- 24590998
TI  - Rivaroxaban-induced epidural hematoma and cauda equina syndrome after total knee
      arthroplasty: a case report.

PMID- 24590999
TI  - Aspergillus spondylodiscitis in an immunocompetent patient following spinal
      anesthesia.

PMID- 24591000
TI  - Minimally invasive anterior lumbar interbody fusion for adjacent segment disease
      after posterior lumbar fusion.

PMID- 24591001
TI  - Lumbar discectomy via Wiltse approach.

PMID- 24591002
TI  - Can we change the past for colorectal cancer patients and how do we move forward?

PMID- 24591003
TI  - Zinc modulates high glucose-induced apoptosis by suppressing oxidative stress in
      renal tubular epithelial cells.
AB  - Hyperglycemia is a characteristic of diabetic nephropathy, inducing renal tubular
      cell apoptosis by eliciting oxidative stress and inflammation. Zinc (Zn) is known
      as an essential trace element in many enzymes and proteins involved in
      antioxidant defenses, electron transport, and exerting antiapoptotic or
      cytoprotective effects. In this study, the underlying mechanisms involved in the
      protective effects of Zn on high glucose-induced cytotoxicity were explored using
      cultured renal tubular epithelial cells (NRK-52E). The authors discovered that Zn
      supplementation inhibited high glucose (HG)-induced NRK-52E cell apoptosis by
      attenuating reactive oxygen species production, inhibiting HG-induced caspase-3
      and caspase-9 activation, and inhibiting the release of cytochrome c from
      mitochondria to the cytosol. Further analysis revealed that Zn supplementation
      facilitated cell survival through increasing nuclear translocation of NF-E2
      related factor 2 (Nrf2), leading to increased regulation of levels of two
      antioxidant enzymes, hemeoxygenase-1 and glutamate cysteine ligase, which
      provided an adaptive survival response against the HG-induced oxidative
      cytotoxicity. Moreover, the Zn-mediated increases in Nrf2 activity were
      suppressed by the pharmacological inhibition of Akt or extracellular signal
      regulated kinase 1/2. Taken together, these findings suggest that Zn
      antiapoptosis capacity through the activation of Akt and ERK signal pathways
      leads to Nrf2 activation and, subsequently, Nrf2 target gene induction, thereby
      protecting the NRK-52E cells from HG-induced apoptosis.

PMID- 24591004
TI  - A multifaceted secondary structure mimic based on piperidine-piperidinones.
AB  - Minimalist secondary structure mimics are typically made to resemble one
      interface in a protein-protein interaction (PPI), and thus perturb it. We
      recently proposed suitable chemotypes can be matched with interface regions
      directly, without regard for secondary structures. Here we describe a modular
      synthesis of a new chemotype 1, simulation of its solution-state conformational
      ensemble, and correlation of that with ideal secondary structures and real
      interface regions in PPIs. Scaffold 1 presents amino acid side-chains that are
      quite separated from each other, in orientations that closely resemble ideal
      sheet or helical structures, similar non-ideal structures at PPI interfaces, and
      regions of other PPI interfaces where the mimic conformation does not resemble
      any secondary structure. 68 different PPIs where conformations of 1 matched well
      were identified. A new method is also presented to determine the relevance of a
      minimalist mimic crystal structure to its solution conformations. Thus DLD-1 faf
      crystallized in a conformation that is estimated to be 0.91 kcal mol(-1) above
      the minimum energy solution state.

PMID- 24591008
TI  - Outlook and emerging semiconducting materials for ambipolar transistors.
AB  - Ambipolar or bipolar transistors are transistors in which both holes and
      electrons are mobile inside the conducting channel. This device allows switching
      among several states: the hole-dominated on-state, the off-state, and the
      electron-dominated on-state. In the past year, it has attracted great interest in
      exotic semiconductors, such as organic semiconductors, nanostructured materials,
      and carbon nanotubes. The ability to utilize both holes and electrons inside one
      device opens new possibilities for the development of more compact complementary
      metal-oxide semiconductor (CMOS) circuits, and new kinds of optoelectronic
      device, namely, ambipolar light-emitting transistors. This progress report
      highlights the recent progresses in the field of ambipolar transistors, both from
      the fundamental physics and application viewpoints. Attention is devoted to the
      challenges that should be faced for the realization of ambipolar transistors with
      different material systems, beginning with the understanding of the importance of
      interface modification, which heavily affects injections and trapping of both
      holes and electrons. The recent development of advanced gating applications,
      including ionic liquid gating, that open up more possibility to realize ambipolar
      transport in materials in which one type of charge carrier is highly dominant is
      highlighted. Between the possible applications of ambipolar field-effect
      transistors, we focus on ambipolar light-emitting transistors. We put this new
      device in the framework of its prospective for general lightings, embedded
      displays, current-driven laser, as well as for photonics-electronics
      interconnection. 

PMID- 24591009
TI  - Enhancing the performance of solution-processed n-type organic field-effect
      transistors by blending with molecular "aligners".
AB  - A novel approach to enhancing the performance of solution-processed n-type
      organic field-effect transistors by using trace amounts of molecular "aligners"
      to manipulate the assembly of "matrix" molecules in thin films is demonstrated.
      The device performance is one order of magnitude higher in 1wt% blended thin
      films than that in neat films, which correlates to an induced change of preferred
      orientation of the in-plane pi-stacking molecules upon blending. 

PMID- 24591010
TI  - Tetrazole-based, anhydrous proton exchange membranes for fuel cells.
AB  - A tetrazole-based polymer electrolyte membrane showed high conductivity at 20-120
      degrees C under dry conditions, offering the potential to dramatically simplify
      fuel cells for many applications over a wide temperature range without the need
      for cumbersome humidification and pressurization. 

PMID- 24591015
TI  - Toward development of interleukin-11 as a medical countermeasure for use in
      radiological/nuclear emergencies.

PMID- 24591016
TI  - Proinflammatory progranulin antibodies in inflammatory bowel diseases.
AB  - BACKGROUND: Recently, we identified neutralizing autoantibodies against
      progranulin (PGRN) in a wide spectrum of rheumatic diseases including cases with
      enteropathic spondylarthritis. PGRN is a secreted protein with strong anti
      inflammatory effects, believed to be mediated by the direct inhibition of TNF
      receptors 1&2. Given the central role of TNF-alpha as proinflammatory cytokine, a
      neutralizing antibody directed against its physiologic antagonist PGRN might
      entertain a proinflammatory environment. OBJECTIVE: The aim of the present study
      was to investigate a possible occurrence of PGRN-antibodies (PGRN-Abs) in
      inflammatory bowel disease (IBD), and to investigate a possible pathogenic
      effect. MATERIALS AND METHODS: Sera samples of 141 patients with Crohn's disease
      (CD) and of 71 patients with ulcerative colitis (UC) were tested for PGRN-Abs by
      ELISA. PGRN plasma levels were detected by ELISA. Proinflammatory effects of
      progranulin-antibodies were analyzed by TNF-alpha-mediated cytotoxicity assays
      using HT29 cells and by examination of possible effects of PGRN and of PGRN
      antibodies on TNF-alpha-induced downmodulation of FOXP3 expression in
      CD4(+)CD25(hi) Tregs. RESULTS: PGRN-Abs were found in sera of 23/141 (16.31%)
      patients with CD, and 15/71 (21.13%) patients with UC. PGRN-Abs were more
      frequent than anti-neutrophil cytoplasmic autoantibodies (ANCAs) in UC, but less
      frequent than anti-Saccharomyces cerevisiae antibodies (ASCAs) in CD. PGRN-Abs
      belonged mostly to IgG1 (71.1%) and IgA (26.3%). They occurred in relevant titres
      and had significant neutralizing effects on PGRN plasma levels. Cytotoxicity
      assays comparing PGRN-antibody-positive sera with negative sera from matched
      patients with IBD showed a proinflammatory effect of PGRN-Abs on HT29 cells.
      Moreover, PGRN-antibodies led to an increase of TNF-alpha-induced downmodulation
      of FOXP3 in CD4(+)CD25(hi) Tregs. CONCLUSION: The results suggest that PGRN-Abs
      occur frequently in CD and UC, and have a proinflammatory effect.

PMID- 24591017
TI  - DEPDC5 mutations in genetic focal epilepsies of childhood.
AB  - Recent studies reported DEPDC5 loss-of-function mutations in different focal
      epilepsy syndromes. Here we identified 1 predicted truncation and 2 missense
      mutations in 3 children with rolandic epilepsy (3 of 207). In addition, we
      identified 3 families with unclassified focal childhood epilepsies carrying
      predicted truncating DEPDC5 mutations (3 of 82). The detected variants were all
      novel, inherited, and present in all tested affected (n=11) and in 7 unaffected
      family members, indicating low penetrance. Our findings extend the phenotypic
      spectrum associated with mutations in DEPDC5 and suggest that rolandic epilepsy,
      albeit rarely, and other nonlesional childhood epilepsies are among the
      associated syndromes.

PMID- 24591018
TI  - Observation of CO2 and solvent adduct ions during negative mode electrospray
      ionization Fourier transform ion cyclotron resonance mass spectrometric analysis
      of monohydric alcohols.
AB  - RATIONALE: Monohydric alcohols are common in natural products, bio-oils, and
      medicine. We have found that monohydric alcohols can form O3 (ions containing
      three oxygen atoms) and O4 adduct ions in negative electrospray ionization (ESI)
      Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS), which
      would significantly affect the composition analysis of alcohols, especially in a
      complex mixture. It is necessary to study the reaction pathways and the method to
      eliminate or reduce the 'artifact' adducts. METHODS: Octadecanol, cholesterol,
      squalanol and two complex monohydric alcohol mixtures were selected as model
      compounds. These samples were subjected to negative ion ESI FT-ICR MS analysis.
      The composition and formation mechanism of adducts were studied by the ultrahigh
      resolution accurate mass measurement for elemental composition, along with the
      MS(2) isolation and collision-induced dissociation (CID) experiments for
      structural determination. RESULTS: The reaction pathway of O3 adduct formation is
      the coupling of a monohydric alcohol ion with a CO2 to form a stable O3 ionic
      species by likely a covalent bond (source of CO2 is not clear). The O4 species
      are formed by O3 ionic species adducted with an alcohol molecule of the solvent,
      such as methanol or ethanol, by likely a hydrogen bond. These adduct ions could
      be eliminated or reduced by increasing collision energy. However, excessive
      collision energy would fragment monohydric alcohol ions. CONCLUSIONS: The
      formation mechanisms of O3 and O4 adducts from monohydric alcohols in negative
      ion ESI FT-ICR MS were proposed. The solvent adduction effects can be eliminated
      or reduced by optimizing the collision energy of CID in FT-ICR MS.

PMID- 24591019
TI  - Laser ablation based bioimaging with simultaneous elemental and molecular mass
      spectrometry: towards spatially resolved speciation analysis.
AB  - RATIONALE: Biological functions of metals are not only specified by the element
      itself, but also by its chemical form and by its organ, cell and subcellular
      location. The developed laser ablation based setup enables spatially resolved
      analysis with simultaneous elemental and molecular mass spectrometry (MS) and
      promises therefore localization, identification and quantification of metal or
      heteroelement-containing species in biological samples such as tissue sections.
      METHODS: A UV laser ablation (LA) system is hyphenated in parallel both with an
      elemental and a molecular mass spectrometer via flow splitted transfer lines to
      simultaneously obtain data from both of the mass spectrometers. Elemental MS was
      performed using inductively coupled plasma (ICP)-MS, whereas atmospheric pressure
      chemical ionization (APCI)-MS with an orbitrap mass analyzer was utilized for
      molecular MS. RESULTS: Simultaneous elemental and molecular MS imaging with high
      lateral resolution down to 25 um was presented for the staining agents eosin Y
      and haematoxylin as well as for the chemotherapy drug cisplatin in thin tissue
      sections. For molecular MS, target compounds were identified by their exact
      masses and by characteristic fragment ions. CONCLUSIONS: The first simultaneous
      elemental and molecular MS imaging approach based on laser ablation sampling was
      introduced for spatially resolved speciation analysis. The combination of the
      advantages of LA-ICP-MS such as low detection limits and high spatial resolution
      with information on the chemical identity promises not only localization of
      metals, but also identification of metal species in biological samples.
      Therefore, this novel technique opens up new possibilities to address complex
      challenges in life science research.

PMID- 24591020
TI  - Ambient molecular imaging by laser ablation atmospheric pressure chemical
      ionization mass spectrometry.
AB  - RATIONALE: The functions and properties of compounds are not only specified by
      their chemical structures, but also by their location inside a sample. Mass
      spectrometry is a powerful tool for imaging, whereby the kind of sample and
      compound depend on the used sampling and ionization methods. The developed laser
      ablation mass spectrometry method delivers high resolution images of small
      molecules in native samples. METHODS: A UV laser ablation (LA) system was
      combined with an atmospheric pressure chemical ionization (APCI) mass
      spectrometer. The spatially resolved sampling was performed by focusing the 213
      nm laser beam onto a sample. The fine aerosol generated by the ns pulsed laser
      irradiation was then transported to the APCI mass spectrometer by a nitrogen
      stream. In the APCI source, post-ionization was accomplished by a corona
      discharge. The resulting ions were detected with an orbitrap mass spectrometer.
      RESULTS: The properties of the novel LA-APCI-MS setup are demonstrated by
      spatially resolved analysis of several samples including tablets, TLC plates and
      dried droplets. The target compounds are detected with high spatial and mass
      resolution. For higher molecular weight compounds like thyroxine, fragmentation
      was observed, whereas small molecules like caffeine stayed intact. CONCLUSIONS:
      LA-APCI-MS is introduced as an ambient molecular mass spectral imaging method for
      molecules with high resolution in space and mass. The combination of two
      independent instruments offers flexible ion source and mass analyzer exchange and
      therefore LA-APCI-MS opens up new possibilities for molecular imaging under
      ambient conditions.

PMID- 24591021
TI  - Comparison of isotopic variability in proteinaceous tissues of a domesticated
      herbivore: a baseline for zooarchaeological investigation.
AB  - RATIONALE: A variety of metabolic, dietary and climatic influences on isotopic
      variation have been established in mammalian hair. The relevance of these factors
      to collagen isotopic composition is unknown, but would be of great interest to
      zooarchaeological analyses of faunal skeletal tissue. METHODS: The relationships
      between carbon (delta(13)C), nitrogen (delta(15)N), non-exchangeable hydrogen
      (delta(2)H) and oxygen (delta(18)O) values of defatted, demineralised and
      gelatinised bone collagen and defatted wool keratin from two sheep flocks (n =
      20, 5) in the UK were investigated, including testing for the effects of
      nutritional plane, sex, pregnancy and season of sample collection. The sulfur
      composition (delta(34)S values) was also investigated for tissues from the
      smaller flock. RESULTS: Bulk collagen was enriched in (13)C over bulk keratin by
      2.0 - 2.70/00 and in (2)H by 29 - 400/00 but depleted in (18)O relative to
      keratin by 1.80/00. Differences in delta(15)N values were within experimental
      error. The collagen samples were generally more enriched in (34)S than keratin,
      but this was very variable. Pregnancy, sex and season, but not nutritional plane,
      significantly affected isotope values but did not change overall keratin-collagen
      relationships. CONCLUSIONS: This dataset provides a baseline measure of
      variability and comparability for isotopic investigations into origin and
      husbandry conditions in archaeological sheep tissues, both collagen and keratin.

PMID- 24591022
TI  - Measurement of delta18O and delta2H values of fluid inclusion water in
      speleothems using cavity ring-down spectroscopy compared with isotope ratio mass
      spectrometry.
AB  - RATIONALE: The hydrogen and oxygen isotopic analyses (delta(2)H and delta(18)O
      values) of water trapped within speleothem carbonate (fluid inclusions) have
      traditionally been conducted utilizing dual-inlet isotope ratio mass spectrometry
      (IRMS) or continuous-flow (CF)-IRMS methods. The application of cavity ring-down
      spectroscopy (CRDS) to the delta(2)H and delta(18)O analysis of water in fluid
      inclusions has been investigated at the University of Miami as an alternative
      method to CF-IRMS. METHODS: An extraction line was developed to recover water
      from the fluid inclusions consisting of a crusher, sample injection port and an
      expansion volume (either 100 or 50 cm(3)) directly connected to the CRDS
      instrument. Tests were conducted to determine the reproducibility of standard
      water injections and crushes. In order to compare results with conventional
      analytical methods, samples were analyzed both at the University of Miami (CRDS
      method) and at the Vrije Universiteit Amsterdam (CF-IRMS method). RESULTS: The
      analytical reproducibility of speleothem samples crushed on the Miami Device
      demonstrates an average external standard deviation of 0.5 and 2.0 0/00 for
      delta(18)O and delta(2)H values, respectively. Sample data are shown to fall near
      the global meteoric water line, supporting the validity of the method. Three
      different samples were analyzed at Vrije Universiteit Amsterdam and the
      University of Miami in order to compare the performance of each laboratory. The
      average offset between the two laboratories is 0.7 0/00 for delta(18)O and 2.5
      0/00 for delta(2)H. CONCLUSIONS: The advantage of CRDS is that the system is a
      low-cost alternative to CF-IRMS for fluid inclusion isotope analysis. The CRDS
      method demonstrates acceptable precision and good agreement with results from the
      CF-IRMS method. These are promising results for the future application of CRDS to
      fluid inclusion isotope analysis.

PMID- 24591023
TI  - Deglycosylation induces extensive dynamics changes in alpha-amylase revealed by
      hydrogen/deuterium exchange mass spectrometry.
AB  - RATIONALE: N-Linked glycosylation plays important roles in modulating protein
      structure and function. The direct impact of the modification on protein
      conformation is not yet well understood. METHODS: Here we probed the dynamic
      changes following Endo H trimming of high mannose glycans in alpha-amylase by
      means of amide hydrogen/deuterium exchange mass spectrometry. RESULTS: The
      results revealed that deglycosylation elicited extensive alterations in backbone
      dynamics, affecting regions both adjacent to and distal from the glycosylation
      site. CONCLUSIONS: The overall exchange rate is reduced in the glycosylated
      state, which indicates rigidity enhancement due to the attached carbohydrates.

PMID- 24591024
TI  - Laser desorption/ionization mass spectrometric analysis of folic acid, vancomycin
      and Triton(r) X-100 on variously functionalized carbon nanotubes.
AB  - RATIONALE: Carbon nanotubes (CNTs) have been ascertained to constitute versatile
      assisting matrices for laser desorption/ionization mass spectrometric analysis of
      different molecules. The functionalization thereof can lead to obtaining laser
      desorption/ionization assisting surfaces that would allow the detection of
      molecules at lower concentration and produce spectra with a better signal-to
      noise ratio. METHODS: Pristine, -OH and -COOH functionalized multi-walled CNTs
      were obtained from commercial suppliers. Gallic or sinapinic acid was attached
      covalently to the CNT surfaces by forming an ester bond. Folic acid, vancomycin
      and Triton((r)) X-100 were used as analytes to examine properties of these new
      assisting surfaces. Mass spectrometry analysis was conducted on a matrix-assisted
      laser desorption/ionization quadrupole time-of-flight (MALDIQTOF) mass
      spectrometer. RESULTS: The functionalization of CNTs was confirmed with Fourier
      transform infrared (FTIR) spectroscopy. The obtained mass spectra revealed that
      all the assisting surfaces are capable of transferring energy to the analytes;
      moreover, the presence of carboxyl groups in the structures of CNTs highly
      enhances their ionization properties. Nevertheless, the presence of sinapinic
      acid on CNT surfaces does not increase their properties to absorb pulse laser
      energy. CONCLUSIONS: The presented assisting surfaces are effective in LDI mass
      analysis of folic acid, vancomycin and Triton((r)) X-100. The appropriate
      functionalization of CNTs can lead to the production of assisting surfaces that
      can become highly effective in the ionization of particular types of analytes.

PMID- 24591025
TI  - Rapid detection and quantification of apolipoprotein L1 genetic variants and
      total levels in plasma by ultra-performance liquid chromatography/tandem mass
      spectrometry.
AB  - RATIONALE: Human genetics studies in African Americans have shown a strong
      correlation between polymorphisms in the ApoL1 gene and chronic kidney disease
      (CKD). To gain further insight into the etiology of ApoL1-associated kidney
      diseases, the determination of circulating levels of both wild type as well as
      ApoL1 variants could be of significant use. To date, antibodies that discriminate
      between all three ApoL1 variant forms (wild type, G1 and G2) are not available.
      We aimed to develop a rapid method for detecting and quantifying ApoL1 variants
      and total levels in plasma. METHODS: Ultra-performance liquid chromatography
      (UPLC) and tandem mass spectrometry (MS/MS) in multiple-reaction monitoring
      acquisition mode was used to quantify ApoL1. RESULTS: We demonstrated that it is
      feasible to detect and quantify ApoL1 variants (wild type, G1 and G2), and total
      ApoL1 concentrations in plasma. ApoL1 genotypes determined by LC/MS agreed
      perfectly with the traditional method DNA sequencing for 74 human subjects. The
      method exhibited at least three orders of linearity with a lower limit of
      quantification of 10 nM. Moreover, the method can readily be multiplexed for the
      quantification of a panel of protein markers in a single sample. CONCLUSIONS: The
      method reported herein obviates the need to perform DNA genotyping of ApoL1
      variants, which is of significant value in cases where stored samples are
      unsuitable for DNA analysis. More importantly, the method could potentially be of
      use in the early identification of individuals at risk of developing CKD, and for
      the stratification of patients for treatment with future ApoL1-modifying
      therapies.

PMID- 24591026
TI  - Diamondoid diacids ('O4' species) in oil sands process-affected water.
AB  - RATIONALE: As a by-product of oil sands extraction, large volumes of oil sands
      process water (OSPW) are generated, which are contaminated with a large range of
      water-soluble organic compounds. The acids are thought to be derived from
      hydrocarbons via natural biodegradation pathways such as alpha- and beta
      oxidation of alkyl substituents, which could produce mono- and diacids, for
      example. However, while several monoacids ('O2' species) have been identified,
      the presence of diacids (i.e. 'O4' species) has only been deduced from results
      obtained via Fourier transform infrared (FTIR) spectroscopy, Fourier transform
      ion cyclotron resonance high-resolution mass spectrometry (FTICR-HRMS) and
      nuclear magnetic resonance ((1)H-NMR) spectroscopy and the structures have never
      been confirmed. METHODS: An extract of an OSPW from a Canadian tailings pond was
      analysed and the retention times and the electron ionization mass spectra of some
      analytes were compared with those of bis-methyl esters of authentic diacids by
      gas chromatography * gas chromatography/time-of-flight mass spectrometry
      (GCxGC/TOFMS) in nominal and accurate mass configurations. RESULTS: Two
      diamondoid diacids (3-carboxymethyladamantane-1-carboxylic acid and adamantane
      1,3-dicarboxylic acid) were firmly identified as their bis-methyl esters by
      retention time and mass spectral matching and several other structural isomers
      were more tentatively assigned. Diacids have substantially increased polarity
      over the hydrocarbon and monoacid species from which they probably derive: as
      late members of biodegradation processes they may be useful indicators of
      weathering and ageing, not only of OSPW, but potentially of crude oil residues
      more generally. CONCLUSIONS: Structures of O4 species in OSPW have been
      identified. This confirms pathways of microbial biodegradation, which were only
      postulated previously, and may be a further indication that remediation of OSPW
      toxicity can occur by natural microbial action. The presence and abundance of
      these diacids might therefore be useful as a measure of biodegradation and
      weathering.

PMID- 24591027
TI  - Systematic optimization of ion-pairing agents and hexafluoroisopropanol for
      enhanced electrospray ionization mass spectrometry of oligonucleotides.
AB  - RATIONALE: New methods to enhance the electrospray ionization (ESI) signals are
      essential for low-level analysis of oligonucleotides. We report a systematic
      evaluation comparing 13 ion-pairing agents with and without hexafluoroisopropanol
      to understand their effect on the ion abundance of hetero-oligonucleotides.
      METHODS: A Waters Synapt G2 HDMS quadrupole time-of-flight instrument was used to
      compare oligonucleotide signal intensity with 13 alkylamine ion-pairing agents at
      varying concentrations. The alkylamines that yielded the highest signal intensity
      were further evaluated with hexafluoroisopropanol at concentrations between 5 and
      100 mM. The chemical properties of the solution components and analytes were
      evaluated to identify key factors in predicting optimal mobile phase conditions
      for different classes of oligonucleotides. RESULTS: We identified a series of
      optimized mobile phase systems using diisopropylamine, tripropylamine,
      dimethylbutylamine, methyldibutylamine, and dimethylhexylamine along with 25 to
      50 mM hexafluoroisopropanol that yielded significantly higher MS signal intensity
      for both siRNA and DNA compared with the traditionally used
      triethlyamine/hexafluoroisopropanol system. We explored charge state reduction,
      adduct formation and ESI mechanisms and identify the Henry's Law constant k aq/g
      as a key chemical property in predicting alkylamines that will increase
      oligonucleotide ion intensity. We also find that the hydrophobicity of the
      oligonucleotide plays a major role in choosing ion-pairing agents that will
      increase ion abundance. CONCLUSIONS: This comprehensive and systematic
      optimization finds that the hydrophobicity of the oligonucleotide was a key
      factor in choosing alkylamine ion-pairing agents to increase ESI abundance. We
      identified that diisopropylamine and tripropylamine combined with lower
      concentrations of hexafluoroisopropanol yielded the highest signal intensity for
      these oligonucleotides.

PMID- 24591028
TI  - Low-energy collision-induced dissociation tandem mass spectrometry of 7
      acetonyloxycoumarins.
AB  - RATIONALE: Coumarins are naturally occurring, oxygen-containing heterocycles with
      considerable pharmaceutical potential. For structural elucidation of natural or
      synthetic coumarins, tandem mass spectrometry (MS(n)) represents an essential
      tool. In this study, fragmentation characteristics of twenty-two 7
      acetonyloxycoumarins, having promising anti-inflammatory properties, were
      investigated with low-energy collision-induced dissociation (CID). METHODS:
      Accurate mass measurements were performed on a 12-T Fourier transform ion
      cyclotron resonance (FT-ICR) instrument. Most CID-MS(n) measurements were
      performed on a quadrupole ion trap (QIT) instrument, except some additional CID
      MS(2) measurements performed on the FT-ICR instrument for further confirmation of
      some fragment ions. Positive-ion electrospray ionization (ESI) was employed
      throughout. Density functional theory (DFT) calculations (B3LYP) were carried out
      to analyze putative ion structures/fragmentation channels. RESULTS: The most
      favourable dissociation channel for [M + H](+) ions of 7-acetonyloxycoumarins was
      the elimination of a C3H5O(?) radical (57 Da) from the 7-acetonyloxy group via
      homolytic bond cleavage. The resulting phenolic radical ion was the primary
      fragment ion for the most compounds studied. Losses of even-electron neutrals,
      C3H4O and C3H6O (56 and 58 Da), were also observed. These primary eliminations
      were accompanied with other characteristic neutral losses from the coumarin
      skeleton, including H2O, CO, CO2, and C2H2O (ketene). In addition, propene (C3H6)
      loss was also observed for 4-propyl or 3-ethyl-4-methyl-substituted compounds.
      CONCLUSIONS: The studied coumarins showed interesting characteristics in low
      energy CID due to the presence of a 7-acetonyloxy group, leading to both even-
      and odd-electron product ions. The main dissociation channels observed for each
      compound were highly dependent on the substituents in the benzopyranone ring. The
      present results will advance our knowledge on the dissociation characteristics of
      both synthetic and natural coumarins.

PMID- 24591029
TI  - Dietary protein content affects isotopic carbon and nitrogen turnover.
AB  - RATIONALE: Isotopic turnover quantifies the metabolic renewal process of elements
      in organs and excreta. Knowledge of the isotopic turnover of animal organs and
      excreta is necessary for diet reconstruction via stable isotope analysis, as used
      in animal ecology, palaeontology and food authentication. Effects of dietary
      protein content on the isotopic carbon and nitrogen turnover (i.e. delay,
      representing the time between ingestion and start of renewal, and half-life) are
      unknown for most mammalian organs and excreta. METHODS: To examine the effect of
      dietary protein content on turnover (delay and turnover rate), we fed 18 rats
      either a diet at protein maintenance or above protein maintenance, and quantified
      their isotopic carbon and nitrogen turnover in ten organs and excreta. These
      included the excreta faeces and urine, the visceral organs blood plasma, liver,
      kidney, lung and spleen, the cerebral tissue brain, and the muscular tissues
      heart and muscle. For data analysis, we used piecewise linear/non-linear
      exponential modelling that allows quantifying delay and turnover rate
      simultaneously. RESULTS: Delays were ~0.5 days for carbon and nitrogen turnover
      and were not affected by dietary protein content. Half-lives during the following
      reaction progress were in the range of 1 to 45 days, increasing from excreta to
      visceral organs to muscular and cerebral organs. Rats fed the higher protein
      amount had 30% shorter nitrogen half-lives, and 20% shorter carbon half-lives.
      CONCLUSIONS: The renewal times of organs and excreta depend on the dietary
      protein content. Hence, isotopic diet reconstruction is confronted with variation
      in half-lives within the same organ or excrement, altering the time window
      through which information can be perceived.

PMID- 24591030
TI  - Characterisation of novel alpha-keratin peptide markers for species
      identification in keratinous tissues using mass spectrometry.
AB  - RATIONALE: In ancient and/or damaged artefacts containing keratinous materials,
      the species of origin of the materials can be difficult to identify through
      visual examination; therefore, a minimally destructive methodology for species
      identification is required. While hair fibres from some species have seen
      substantial characterisation, others such as horn or baleen have received little
      or no attention, or lack protein sequences allowing formal identification using
      proteomics techniques. METHODS: We used the PMF method (Peptide Mass
      Fingerprinting with matrix-assisted laser desorption/ionisation time-of-flight
      mass spectrometry (MALDI-TOF-MS)) to catalogue and identify diagnostic peptide
      markers up to the genus level. Sequences were checked using nanoflow liquid
      chromatography/electrospray ionisation tandem mass spectrometry (nanoLC/ESI
      MS/MS) and unidentified peptides were searched against a theoretical database
      generated by substituting amino acids in keratin sequences. RESULTS: Specific
      peptides were identified by m/z and sequences characterised whenever possible for
      a range of species belonging to Bovidae and Camelidae, and for tissues such as
      baleen and horn. The theoretical database allowed an increase in the number of
      peptides of up to 10% in species with little genetic information. CONCLUSIONS: A
      proteomics approach can successfully identify specific markers for the
      identification of materials to the genus level, and should be considered when
      identification by other means is not possible. Identification by PMF is fast,
      reliable and inexpensive.

PMID- 24591031
TI  - Ion mobility mass spectrometry analysis of isomeric disaccharide precursor,
      product and cluster ions.
AB  - RATIONALE: Carbohydrates are highly variable in structure owing to differences in
      their anomeric configurations, monomer stereochemistry, inter-residue linkage
      positions and general branching features. The separation of carbohydrate isomers
      poses a great challenge for current analytical techniques. METHODS: The isomeric
      heterogeneity of disaccharide ions and monosaccharide-glycolaldehyde product ions
      was evaluated using electrospray traveling wave ion mobility mass spectrometry
      (Synapt G2 high-definition mass spectrometer) in both positive and negative ion
      modes. RESULTS: The separation of isomeric disaccharide ions was observed but not
      fully achieved based on their mobility profiles. The mobilities of isomeric
      product ions, the monosaccharide-glycolaldehydes, derived from different
      disaccharide isomers were measured. Multiple mobility peaks were observed for
      both monosaccharide-glycolaldehyde cations and anions, indicating that there was
      more than one structural configuration in the gas phase as verified by NMR in
      solution. More importantly, the mobility patterns for isomeric monosaccharide
      glycolaldehyde product ions were different, which enabled partial
      characterization of their respective disaccharide ions. Abundant disaccharide
      cluster ions were also observed. The results showed that a majority of isomeric
      cluster ions had different drift times and, moreover, more than one mobility peak
      was detected for a number of specific cluster ions. CONCLUSIONS: It is
      demonstrated that ion mobility mass spectrometry is an advantageous method to
      assess the isomeric heterogeneity of carbohydrate compounds. It is capable of
      differentiating different types of carbohydrate ions having identical m/z values
      as well as multiple structural configurations of single compounds.

PMID- 24591032
TI  - Elucidating the sequence of intact bioactive peptides by using electron capture
      dissociation and hot electron capture dissociation in a linear radio-frequency
      quadrupole ion trap.
AB  - RATIONALE: Electron capture dissociation (ECD) is useful tool for sequencing of
      peptides and proteins with post-translational modifications. To increase the
      sequence coverage for peptides and proteins, it is important to develop ECD
      device with high fragmentation efficiency. METHODS: Sequence analysis of intact
      undigested bioactive peptides (3000-5000 Da) was performed by use of electron
      capture dissociation (rf-ECD) and collision-induced dissociation (CID) in a
      linear radio-frequency quadrupole ion trap that was coupled to a time-of-flight
      mass spectrometer. We applied rf-ECD, hot rf-ECD (rf-ECD with high electron
      energy), and CID for intact bioactive peptide ions of various charge states and
      evaluated the sequence coverage of their fragment spectra. RESULTS: Hot rf-ECD
      produced a higher number of c- and z-type fragment ions of modified peptide ions
      as electron energy increased in lower charged peptide ions, and sequence coverage
      greater than 80% was obtained compared with the CID case (40-80%). CONCLUSIONS:
      The result indicates that intact bioactive modified peptides (Ghrelin, ANP) were
      correctly identified by use of hot rf-ECD.

PMID- 24591033
TI  - Photodynamic oxidation of Escherichia coli membrane phospholipids: new insights
      based on lipidomics.
AB  - RATIONALE: The irreversible oxidation of biological molecules, such as lipids,
      can be achieved with a photosensitizing agent and subsequent exposure to light,
      in the presence of molecular oxygen. Although lipid peroxidation is an important
      toxicity mechanism in bacteria, the alterations caused by the photodynamic
      therapy on bacterial phospholipids are still unknown. In this work, we studied
      the photodynamic oxidation of Escherichia coli membrane phospholipids using a
      lipidomic approach. METHODS: E. coli ATCC 25922 were irradiated for 90 min with
      white light (4 mW cm(-2), 21.6 J cm(-2)) in the presence of a tricationic
      porphyrin [(5,10,15-tris(1-methylpyridinium-4-yl)-20-(pentafluorophenyl)porphyrin
      triiodide, Tri-Py(+)-Me-PF]. Lipids were extracted and separated by thin-layer
      chromatography. Phospholipid classes were quantified by phosphorus assay and
      analyzed by electrospray ionization tandem mass spectrometry. Fatty acids were
      analyzed by gas chromatography. Quantification of lipid hydroperoxides was
      performed by FOX2 assay. Analysis of the photodynamic oxidation of a phospholipid
      standard was also performed. RESULTS: Our approach allowed us to see that the
      photodynamic treatment induced the formation of a high amount of lipid
      hydroperoxides in the E. coli lipid extract. Quantification of fatty acids
      revealed a decrease in the unsaturated C16:1 and C18:1 species suggesting that
      oxidative modifications were responsible for their variation. It was also
      observed that photosensitization induced the oxidation of
      phosphatidylethanolamines with C16:1, C18:1 and C18:2 fatty acyl chains, with
      formation of hydroxy and hydroperoxy derivatives. CONCLUSIONS: Membrane
      phospholipids of E. coli are molecular targets of the photodynamic effect induced
      by Tri-Py(+) -Me-PF. The overall change in the relative amount of unsaturated
      fatty acids and the formation of PE hydroxides and hydroperoxides evidence the
      damages in bacterial phospholipids caused by this lethal treatment.

PMID- 24591034
TI  - Solvent-dependent self-assembly behaviour and speciation control of Pd6L8 metallo
      supramolecular cages.
AB  - The C3-symmetric chiral propylated host-type ligands (+/-)-tris(isonicotinoyl)
      tris(propyl)-cyclotricatechylene (L1) and (+/-)-tris(4-pyridyl-4-benzoxy)
      tris(propyl)-cyclotricatechylene (L2) self-assemble with Pd(II) into [Pd6L8](12+)
      metallo-cages that resemble a stella octangula. The self-assembly of the
      [Pd6(L1)8](12+) cage is solvent-dependent; broad NMR resonances and a disordered
      crystal structure indicate no chiral self-sorting of the ligand enantiomers in
      DMSO solution, but sharp NMR resonances occur in MeCN or MeNO2. The
      [Pd6(L1)8](12+) cage is observed to be less favourable in the presence of
      additional ligand, than is its counterpart, where L=(+/-)
      tris(isonicotinoyl)cyclotriguaiacylene (L1 a). The stoichiometry of reactant
      mixtures and chemical triggers can be used to control formation of mixtures of
      homoleptic or heteroleptic [Pd6L8](12+) metallo-cages where L=L1 and L1 a.

PMID- 24591035
TI  - Recurrent microdeletion 2q21.1: report on a new patient with neurological
      disorders.
AB  - Whole genome profiling such as array comparative genomic hybridization has
      identified novel genomic imbalances. Copy number studies led to an explosion of
      the discoveries of new segmental duplication-mediated deletions and duplications.
      These rearrangements are mostly the result of non-allelic homologous
      recombination (NAHR) between low-copy repeats or segmental duplications. We have
      identified an individual with a small, rare deletion on chromosome 2q21.1 with
      psychomotor delay, hyperactivity, and aggressive behavior. The rearranged region
      is flanked by large complex low-copy repeats and includes only five genes:
      GPR148, FAM123C (AMER3), ARHGEF4, FAM168B, and PLEKHB2. The comparison between
      our patient and the cases previously reported in the literature contributes to a
      better definition of genotype-phenotype correlation of 2q21.1 microdeletions.

PMID- 24591036
TI  - Genetic testing using array comparative genomic hybridization may benefit
      newborns with congenital heart disease: study shows aCGH more effective at
      detecting potential genetic causes of CHD than other methods.

PMID- 24591037
TI  - FDA-approved Next-Generation sequencing system could expand clinical genomic
      testing: experts predict MiSeqDx system will make genetic testing more affordable
      for smaller labs.

PMID- 24591039
TI  - Improved conditions for periodate/Schiff's base-based fluorescent staining of
      glycoproteins with dansylhydrazine in SDS-PAGE.
AB  - An improved periodate/Schiff's base based fluorescent stain with dansylhydrazine
      (DH) for glycoproteins in 1D and 2D SDS-PAGE was described. Down to 4-8 ng of
      glycoproteins can be selectively detected within 2 h, which is approximately 16
      fold higher than that of original protocol, but similar to that of Pro-Q Emerald
      488 stain (Invitrogen, Carlsbad, USA). Furthermore, subsequent study of
      deglycosylation, glycoprotein affinity isolation, and LC-MS/MS analysis were
      performed to confirm the specificity of the improved method. As a result,
      improved DH stain may provide a new choice for selective, economic, MS
      compatible, and convenient visualization of gel-separated glycoproteins. 

PMID- 24591040
TI  - Asymmetric decarboxylative 1,4-addition of malonic acid half thioesters to vinyl
      sulfones: highly enantioselective synthesis of 3-monofluoromethyl-3-arylpropanoic
      esters.
AB  - An asymmetric decarboxylative 1,4-addition of malonic acid half thioesters
      (MAHTs) to 2-aryl-substituted vinyl sulfones has been developed, yielding adducts
      with excellent enantioselectivity (up to 97 % ee). In view of tuning pKa values,
      a quinine-based benzyl-substituted thiourea was designed and demonstrated as the
      most efficient catalyst. The enantioselective synthesis of 3-monofluorinated
      analogues of 3-methyl indanone and (+)-turmerone has been accomplished from
      decarboxylative 1,4-addition adducts with satisfactory results. 

PMID- 24591041
TI  - Getting started in the scholarship of teaching and learning: a "how to" guide for
      science academics.
AB  - SoTL stands for the Scholarship of Teaching and Learning. The acronym, said
      "sottle" or "sote-all," describes research that involves rigorous examination of
      teaching and learning by faculty who are actively involved in the educational
      process. The number of natural-science faculty engaged in SoTL is increasing, and
      their important work has broad implications for the measurement and improvement
      of college teaching and learning outcomes. The data show, however, that many
      faculty who conduct SoTL projects in science departments begin their education
      research careers with no training in SoTL research methodologies, and find they
      are working alone, with few colleagues who can nurture (or even understand) their
      efforts. In this article we provide a guide intended to help natural-science
      faculty initiate SoTL projects while they negotiate the mechanics and politics of
      developing and maintaining a SoTL research program in a science department.

PMID- 24591042
TI  - Curriculum and course materials for a forensic DNA biology course.
AB  - The Forensic Science Education Programs Accreditation Commission (FEPAC) requires
      accredited programs offer a "coherent curriculum" to ensure each student gains a
      "thorough grounding of the natural...sciences." Part of this curriculum includes
      completion of a minimum of 15 semester-hours forensic science coursework, nine of
      which can involve a class in forensic DNA biology. Departments that have obtained
      or are pursuing FEPAC accreditation can meet this requirement by offering a stand
      alone forensic DNA biology course; however, materials necessary to instruct
      students are often homegrown and not standardized; in addition, until recently,
      the community lacked commercially available books, lab manuals, and teaching
      materials, and many of the best pedagogical resources were scattered across
      various peer-reviewed journals. The curriculum discussed below is an attempt to
      synthesize this disparate information, and although certainly not the only
      acceptable methodology, the below discussion represents "a way" for synthesizing
      and aggregating this information into a cohesive, comprehensive whole.

PMID- 24591043
TI  - Websites of note.

PMID- 24591045
TI  - Effect of high molecular weight glutenin subunit composition in common wheat on
      dough properties and steamed bread quality.
AB  - BACKGROUND: Steamed bread is a popular staple food in Asia with different flour
      quality requirements from pan bread. Little is known about how glutenin
      characteristics affect steamed bread quality. This work investigated how
      deletions of high-molecular-weight glutenin subunits (HMW-GS) influence gluten
      properties and Chinese steamed bread quality using 16 wheat lines grown in Texas.
      RESULTS: Although similar in protein content (134-140 mg g-1), gluten composition
      and dough properties differed widely among the lines. Compared with non-deletion
      lines, deletion lines had lower (P < 0.05) unextractable polymeric protein (294
      vs 470 mg g-1), HMW-GS/low-molecular-weight glutenin subunit ratio (0.25 vs
      0.41), dough force to extend (0.16 vs 0.44 N) and mixing peak time (2.03 vs 4.52
      min). Deletion lines with HMW-GS composition of 2*/17+_/5+_ and 2*/17+_/2+12
      showed moderate gluten strength (mixing peak time, 1.96-2.94 min; force to
      extend, 0.18-0.23 N) and high dough extensibility (106-129 mm). These lines also
      produced good steamed bread quality (score, 60.8-65.0) with good elasticity and
      crumb structure. CONCLUSION: Deletion at Glu-B1y and/or Glu-D1y loci in high
      strength hard wheat produced good dough properties for steamed bread. This
      suggests that wheat functionality for steamed bread can be improved by
      manipulating HMW-GS composition.

PMID- 24591047
TI  - Leptin does not induce an inflammatory response in the murine placenta.
AB  - Leptin is described as a pro-inflammatory signal in fat tissue, which is released
      from adipocytes and in turn activates immune cells. Also, leptin levels are known
      to be increased in pregnancies complicated with enhanced inflammatory processes
      in the placenta. Hence, we assumed that increased leptin amounts might contribute
      to inducing an inflammatory response in the placenta. To test this hypothesis,
      pregnant mice were continuously infused with recombinant murine leptin s. c. from
      day g13 to g16, resulting in a 3-fold increase of maternal circulating serum
      leptin levels. Dissected placentas were examined for the expression of pro
      inflammatory cytokines IL-6 and TNF-alpha and the anti-inflammatory cytokine IL
      10 using qPCR analysis. No changes were found except for TNF-alpha, which was
      slightly elevated upon leptin stimulation. However, TNF-alpha protein levels were
      not significantly higher in placentas from leptin treated mice. Also, leukocyte
      infiltration in the labyrinth section of placentas was not increased. In summary,
      our data demonstrate for the first time that elevated leptin levels alone do not
      induce an inflammatory response in the placenta. 

PMID- 24591046
TI  - Temporal regulation of Dpp signaling output in the Drosophila wing.
AB  - BACKGROUND: The Decapentaplegic (Dpp) signaling pathway is used in many
      developmental and homeostatic contexts, each time resulting in cellular responses
      particular to that biological niche. The flexibility of Dpp signaling is clearly
      evident in epithelial cells of the Drosophila wing imaginal disc. During larval
      stages of development, Dpp functions as a morphogen, patterning the wing
      developmental field and stimulating tissue growth. A short time later, however,
      as wing-epithelial cells exit the cell cycle and begin to differentiate, Dpp is a
      critical determinant of vein-cell fate. It is likely that the Dpp signaling
      pathway regulates different sets of target genes at these two developmental time
      points. RESULTS: To identify mechanisms that temporally control the
      transcriptional output of Dpp signaling in this system, we have taken a gene
      expression profiling approach. We identified genes affected by Dpp signaling at
      late larval or early pupal developmental time points, thereby identifying
      patterning- and differentiation-specific downstream targets, respectively.
      CONCLUSIONS: Analysis of target genes and transcription factor binding sites
      associated with these groups of genes revealed potential mechanisms by which
      target-gene specificity of the Dpp signaling pathway is temporally regulated. In
      addition, this approach revealed novel mechanisms by which Dpp affects the
      cellular differentiation of wing-veins.

PMID- 24591048
TI  - Quantification of thyroxine and 3,5,3'-triiodo-thyronine in human and animal
      hearts by a novel liquid chromatography-tandem mass spectrometry method.
AB  - Assaying tissue T3 and T4 would provide important information in experimental and
      clinical investigations. A novel method to determine tissue T3 and T4 by HPLC
      coupled to mass spectrometry is described. The major difference vs. previously
      described methods lies in the addition of a derivatization step, that is, to
      convert T3 and T4 into the corresponding butyl esters. The yield of
      esterification was  100% for T3 and 80% for T4. The assay was linear (r>0.99) in
      the range of 0.2-50 ng/ml, accuracy was in the order of 70-75%, and the minimum
      tissue amount needed was in the order of 50 mg, that is, about one order of
      magnitude lower than observed with the same equipment (AB Sciex API 4000 triple
      quadrupole mass spectrometer) if derivatization was omitted. The method allowed
      detection of T3 and T4 in human left ventricle biopsies yielding concentrations
      of 1.51+/-0.16 and 5.94+/-0.63 pmol/g, respectively. In rats treated with
      different dosages of exogenous T3 or T4, good correlations (r>0.90) between
      plasma and myocardial T3 and T4 concentrations were observed, although in
      specific subsets different plasma T4 concentrations were not associated with
      different tissue content in T4. We conclude that this method could provide a
      novel insight into the relationship between plasma and tissue thyroid hormone
      levels. 

PMID- 24591049
TI  - Chemical inducers of systemic immunity in plants.
AB  - Systemic acquired resistance (SAR) is a highly desirable form of resistance that
      protects against a broad-spectrum of related or unrelated pathogens. SAR involves
      the generation of multiple signals at the site of primary infection, which arms
      distal portions against subsequent secondary infections. The last decade has
      witnessed considerable progress, and a number of chemical signals contributing to
      SAR have been isolated and characterized. The diverse chemical nature of these
      chemicals had led to the growing belief that SAR might involve interplay of
      multiple diverse and independent signals. However, recent results suggest that
      coordinated signalling from diverse signalling components facilitates SAR in
      plants. This review mainly discusses organized signalling by two such chemicals,
      glycerol-3-phoshphate and azelaic acid, and the role of basal salicylic acid
      levels in G3P-conferred SAR.

PMID- 24591050
TI  - Contrasting adaptive strategies to terminal drought-stress gradients in
      Mediterranean legumes: phenology, productivity, and water relations in wild and
      domesticated Lupinus luteus L.
AB  - Our understanding of within-species annual plant adaptation to rainfall gradients
      is fragmented. Broad-scale ecological applications of Grime's C-S-R triangle are
      often superficial, while detailed drought physiology tends to be narrow, focusing
      on elite cultivars. The former lack the detail to explain how plants respond,
      while the latter provide little context to investigate trade-offs among traits,
      to explain where/why these might be adaptive. Ecophysiology, combining the
      breadth of the former with the detail of the latter, can resolve this disconnect
      and is applied here to describe adaptive strategies in the Mediterranean legume
      Lupinus luteus. Wild and domesticated material from low- and high-rainfall
      environments was evaluated under contrasting terminal drought. These opposing
      environments have selected for contrasting, integrated, adaptive strategies. Long
      season, high-rainfall habitats select for competitive (C) traits: delayed
      phenology, high above- and below-ground biomass, productivity, and fecundity,
      leading to high water-use and early stress onset. Terminal drought-prone
      environments select for the opposite: ruderal (R) traits that facilitate drought
      escape/avoidance but limit reproductive potential. Surprisingly, high-rainfall
      ecotypes generate lower critical leaf water potentials under water deficit,
      maintaining higher relative water content than the latter. Given that L. luteus
      evolved in sandy, low-water-holding capacity soils, this represents a bet-hedging
      response to intermittent self-imposed water-deficits associated with a strongly C
      selected adaptive strategy that is therefore redundant in R-selected low-rainfall
      ecotypes. Domesticated L. luteus is even more R-selected, reflecting ongoing
      selection for early maturity. Introgression of appropriate C-selected adaptive
      traits from wild germplasm may widen the crop production range. 

PMID- 24591051
TI  - Cyclic GMP is involved in auxin signalling during Arabidopsis root growth and
      development.
AB  - The second messenger cyclic guanosine 3',5'-monophosphate (cGMP) plays an
      important role in plant development and responses to stress. Recent studies
      indicated that cGMP is a secondary signal generated in response to auxin
      stimulation. cGMP also mediates auxin-induced adventitious root formation in mung
      bean and gravitropic bending in soybean. Nonetheless, the mechanism of the
      participation of cGMP in auxin signalling to affect these growth and
      developmental processes is largely unknown. In this report we provide evidence
      that indole-3-acetic acid (IAA) induces cGMP accumulation in Arabidopsis roots
      through modulation of the guanylate cyclase activity. Application of 8-bromo-cGMP
      (a cell-permeable cGMP derivative) increases auxin-dependent lateral root
      formation, root hair development, primary root growth, and gene expression. In
      contrast, inhibitors of endogenous cGMP synthesis block these processes induced
      by auxin. Data also showed that 8-bromo-cGMP enhances auxin-induced degradation
      of Aux/IAA protein modulated by the SCF(TIR1) ubiquitin-proteasome pathway.
      Furthermore, it was found that 8-bromo-cGMP is unable to directly influence the
      auxin-dependent TIR1-Aux/IAA interaction as evidenced by pull-down and yeast two
      hybrid assays. In addition, we provide evidence for cGMP-mediated modulation of
      auxin signalling through cGMP-dependent protein kinase (PKG). Our results suggest
      that cGMP acts as a mediator to participate in auxin signalling and may govern
      this process by PKG activity via its influence on auxin-regulated gene expression
      and auxin/IAA degradation. 

PMID- 24591052
TI  - UV-B inhibition of hypocotyl growth in etiolated Arabidopsis thaliana seedlings
      is a consequence of cell cycle arrest initiated by photodimer accumulation.
AB  - Ultraviolet (UV) radiation is an important constituent of sunlight that
      determines plant morphology and growth. It induces photomorphogenic responses but
      also causes damage to DNA. Arabidopsis mutants of the endonucleases that function
      in nucleotide excision repair, xpf-3 and uvr1-1, showed hypersensitivity to UV-B
      (280-320nm) in terms of inhibition of hypocotyl growth. SOG1 is a transcription
      factor that functions in the DNA damage signalling response after gamma
      irradiation. xpf mutants that carry the sog1-1 mutation showed hypocotyl growth
      inhibition after UV-B irradiation similar to the wild type. A DNA replication
      inhibitor, hydroxyurea (HU), also inhibited hypocotyl growth in etiolated
      seedlings, but xpf-3 was not hypersensitive to HU. UV-B irradiation induced
      accumulation of the G2/M-specific cell cycle reporter construct CYCB1;1-GUS in
      wild-type Arabidopsis seedlings that was consistent with the expected
      accumulation of photodimers and coincided with the time course of hypocotyl
      growth inhibition after UV-B treatment. Etiolated mutants of UVR8, a recently
      described UV-B photoreceptor gene, irradiated with UV-B showed inhibition of
      hypocotyl growth that was not different from that of the wild type, but they
      lacked UV-B-specific expression of chalcone synthase (CHS), as expected from
      previous reports. CHS expression after UV-B irradiation was not different in xpf
      3 compared with the wild type, nor was it altered after HU treatment. These
      results suggest that hypocotyl growth inhibition by UV-B light in etiolated
      Arabidopsis seedlings, a photomorphogenic response, is dictated by signals
      originating from UV-B absorption by DNA that lead to cell cycle arrest. This
      process occurs distinct from UVR8 and its signalling pathway responsible for CHS
      induction. 

PMID- 24591053
TI  - Introgression of two chromosome regions for leaf photosynthesis from an indica
      rice into the genetic background of a japonica rice.
AB  - Increases in rates of individual leaf photosynthesis (P n) are critical for
      future increases of rice yields. A previous study, using introgression lines
      derived from a cross between indica cultivar Habataki, with one of the highest
      recorded values of P n, and the Japanese elite cultivar Koshihikari, identified
      four QTLs (qCAR4, qCAR5, qCAR8, and qCAR11) that affect P n. The present study
      examined the combined effect of qCAR4 and qCAR8 on P n in the genetic background
      of Koshihikari. The pyramided near-isogenic line NIL(qCAR4+qCAR8) showed higher P
      n than both NIL(qCAR4) and NIL(qCAR8), equivalent to that of Habataki despite
      being due to only two out of the four QTLs. The high P n of NIL(qCAR4+qCAR8) may
      be attributable to the high leaf nitrogen content, which may have been inherited
      from NIL(qCAR4), to the large hydraulic conductance due to the large root surface
      area from NIL(qCAR4), and to the high hydraulic conductivity from NIL(qCAR8). It
      might be also attributable to high mesophyll conductance, which may have been
      inherited from NIL(qCAR4). The induction of mesophyll conductance and the high
      leaf nitrogen content and high hydraulic conductivity could not be explained in
      isolation from the Koshihikari background. These results suggest that QTL
      pyramiding is a useful approach in rice breeding aimed at increasing P n. 

PMID- 24591054
TI  - Synthetic metabolons for metabolic engineering.
AB  - It has been proposed that enzymes can associate into complexes (metabolons) that
      increase the efficiency of metabolic pathways by channelling substrates between
      enzymes. Metabolons may increase flux by increasing the local concentration of
      intermediates, decreasing the concentration of enzymes needed to maintain a given
      flux, directing the products of a pathway to a specific subcellular location or
      minimizing the escape of reactive intermediates. Metabolons can be formed by
      relatively loose non-covalent protein-protein interaction, anchorage to
      membranes, and (in bacteria) by encapsulation of enzymes in protein-coated
      microcompartments. Evidence that non-coated metabolons are effective at
      channelling substrates is scarce and difficult to obtain. In plants there is
      strong evidence that small proportions of glycolytic enzymes are associated with
      the outside of mitochondria and are effective in substrate channelling. More
      recently, synthetic metabolons, in which enzymes are scaffolded to synthetic
      proteins or nucleic acids, have been expressed in microorganisms and these
      provide evidence that scaffolded enzymes are more effective than free enzymes for
      metabolic engineering. This provides experimental evidence that metabolons may
      have a general advantage and opens the way to improving the outcome of metabolic
      engineering in plants by including synthetic metabolons in the toolbox. 

PMID- 24591056
TI  - Apoplastic and symplastic phloem loading in Quercus robur and Fraxinus excelsior.
AB  - Whereas most of the research on phloem loading is performed on herbaceous plants,
      less is known about phloem loading strategies in trees. In this study, the phloem
      loading mechanisms of Quercus robur and Fraxinus excelsior were analysed. The
      following features were examined: the minor vein structure, the sugar
      concentrations in phloem sap by the laser-aphid-stylet technique, the
      distribution of photoassimilates in the mesophyll cells by non-aqueous
      fractionation, gradients of sugar concentrations and osmotic pressure, and the
      expression of sucrose transporters. The minor vein configurations of Q. robur and
      F. excelsior belong to the open type. Quercus robur contained companion cells in
      the minor veins whereas F. excelsior showed intermediary cells in addition to
      ordinary companion cells. The main carbon transport form in Q. robur was sucrose
      (~1M). In F. excelsior high amounts of raffinose and stachyose were also
      transported. However, in both tree species, the osmolality of phloem sap was
      higher than the osmolality of the mesophyll cells. The concentration gradients
      between phloem sap and the cytoplasm of mesophyll cells for sucrose were 16-fold
      and 14-fold for Q. robur and F. excelsior, respectively. Independent of the type
      of translocated sugars, sucrose transporter cDNAs were cloned from both species.
      The results indicate that phloem loading of sucrose and other metabolites must
      involve active loading steps in both tree species. Quercus robur seems to be an
      apoplastic phloem loader while F. excelsior shows indications of being a
      symplastic or mixed symplastic-apoplastic phloem loader.

PMID- 24591057
TI  - SEORious business: structural proteins in sieve tubes and their involvement in
      sieve element occlusion.
AB  - The phloem provides a network of sieve tubes for long-distance translocation of
      photosynthates. For over a century, structural proteins in sieve tubes have
      presented a conundrum since they presumably increase the hydraulic resistance of
      the tubes while no potential function other than sieve tube or wound sealing in
      the case of injury has been suggested. Here we summarize and critically evaluate
      current speculations regarding the roles of these proteins. Our understanding
      suffers from the suggestive power of images; what looks like a sieve tube plug on
      micrographs may not actually impede translocation very much. Recent reports of an
      involvement of SEOR (sieve element occlusion-related) proteins, a class of P
      proteins, in the sealing of injured sieve tubes are inconclusive; various lines
      of evidence suggest that, in neither intact nor injured plants, are SEORs
      determinative of translocation stoppage. Similarly, the popular notion that P
      proteins serve in the defence against phloem sap-feeding insects is unsupported
      by empirical facts; it is conceivable that in functional sieve tubes, aphids
      actually could benefit from inducing a plug. The idea that rising cytosolic
      Ca(2+) generally triggers sieve tube blockage by P-proteins appears widely
      accepted, despite lacking experimental support. Even in forisomes, P-protein
      assemblages restricted to one single plant family and the only Ca(2+)-responsive
      P-proteins known, the available evidence does not unequivocally suggest that plug
      formation is the cause rather than a consequence of translocation stoppage. We
      conclude that the physiological roles of structural P-proteins remain elusive,
      and that in vivo studies of their dynamics in continuous sieve tube networks
      combined with flow velocity measurements will be required to (hopefully) resolve
      this scientific roadblock. 

PMID- 24591055
TI  - A novel lily anther-specific gene encodes adhesin-like proteins associated with
      exine formation during anther development.
AB  - The anther-specific gene LLA1271 isolated from lily (Lilium longiflorum Thunb.)
      anthers is novel and exists in two forms. The protein encoded by LLA1271 may
      represent an adhesin-like protein first found in higher plants. The protein
      contains a typical N-terminal signal peptide followed by a highly conserved
      repeat domain. The LLA1271 gene is temporally expressed at the phase of
      microspore development. RNA blot and RNA in situ hybridization analyses
      demonstrated that the gene was expressed both in the tapetum and in the
      microspore. The gene is endo- and exogenously induced by gibberellin. Studies
      with the gibberellin biosynthesis inhibitor uniconazole and an inhibitor of
      ethylene activity, 2,5-norbornadien (NBD), revealed that LLA1271 is negatively
      regulated by ethylene, and a cross-talk of regulation between gibberellin and
      ethylene occurs in young anthers. The treatment with NBD caused the tapetum to
      become densely cytoplasmic and highly polarized, whereas uniconazole arrested
      tapetal development in a state close to that of a tapetum without treatment. The
      LLA1271 protein is heat stable and heterogeneous. An immunoblot of separated
      protein fractions of the anther revealed that the LLA1271 protein was detected in
      protein fraction of the microspore released from the cell wall by treatment with
      either 0.5% or 2% Triton X-100. Ectopic expression of LLA1271 resulted in
      impaired stamen and low pollen germination. Scanning electron microscopy of
      TAP::LLA1271 pollen showed distorted exine formation and patterning. The LLA1271
      protein once synthesized in both the tapetum and microspore is secreted and
      deposited on the surface of microspores, moderately affecting exine formation and
      patterning. 

PMID- 24591058
TI  - Acclimation of C4 metabolism to low light in mature maize leaves could limit
      energetic losses during progressive shading in a crop canopy.
AB  - C4 plants have a biochemical carbon-concentrating mechanism that increases CO2
      concentration around Rubisco in the bundle sheath. Under low light, the activity
      of the carbon-concentrating mechanism generally decreases, associated with an
      increase in leakiness (phi), the ratio of CO2 retrodiffusing from the bundle
      sheath relative to C4 carboxylation. This increase in phi had been theoretically
      associated with a decrease in biochemical operating efficiency (expressed as ATP
      cost of gross assimilation, ATP/GA) under low light and, because a proportion of
      canopy photosynthesis is carried out by shaded leaves, potential productivity
      losses at field scale. Maize plants were grown under light regimes representing
      the cycle that leaves undergo in the canopy, whereby younger leaves initially
      developed under high light and were then re-acclimated to low light (600 to 100
      MUE.m(-2).s(-1) photosynthetically active radiation) for 3 weeks. Following re
      acclimation, leaves reduced rates of light-respiration and reached a status of
      lower phi, effectively optimizing the limited ATP resources available under low
      photosynthetically active radiation. Direct estimates of respiration in the
      light, and ATP production rate, allowed an empirical estimate of ATP production
      rate relative to gross assimilation to be derived. These values were compared to
      modelled ATP/GA which was predicted using leakiness as the sole proxy for ATP/GA,
      and, using a novel comprehensive biochemical model, showing that irrespective of
      whether leaves are acclimated to very low or high light intensity, the
      biochemical efficiency of the C4 cycle does not decrease at low
      photosynthetically active radiation. 

PMID- 24591059
TI  - FDA bridging analyses confirmed in clinical trial.

PMID- 24591060
TI  - EURObservational Research Programme: a worldwide registry on peripartum
      cardiomyopathy (PPCM) in conjunction with the Heart Failure Association of the
      European Society of Cardiology Working Group on PPCM.
AB  - BACKGROUND: The EURObservational Research Programme is a rolling programme of
      cardiovascular registries and surveys of the European Society of Cardiology
      (ESC). These registries will provide information on the nature of cardiovascular
      disease and its management. This manuscript provides an update on new literature
      on peripartum cardiomyopathy (PPCM), published since the 2010 Position Statement
      from the Heart Failure Association of the European Society of Cardiology Working
      Group on PPCM, and describes a new registry on this under-recognized condition.
      Peripartum cardiomyopathy is an idiopathic cardiomyopathy presenting with heart
      failure secondary to left ventricular systolic dysfunction towards the end of the
      pregnancy, or in the months following delivery, where no other cause for heart
      failure is found. AIMS: The PPCM Registry aims to describe disease presentation,
      comorbidities, diagnostic and therapeutic management of patients with PPCM, as
      well as information on their offspring. Centres not only from ESC and ESC
      affiliated countries, but from around the world, are encouraged to participate.
      METHODS: A prospective registry on patients presenting with PPCM. At the time of
      writing, approximately 100 patients have been enrolled from 20 countries. All
      data entry is online via secure passwords and is supported by well-trained
      information technology personnel. CONCLUSION: The EURObservational Research
      Programme will allow a comparison of women from around the world, from different
      ethnic backgrounds, presenting with PPCM and will report on their 6 month and 12
      month outcomes. The study aims to include 1000 patients and follow them for 1
      year. New centres volunteering to participate in the study will be welcomed.

PMID- 24591061
TI  - Prediagnostic lifestyle factors and survival after colon and rectal cancer
      diagnosis in the National Institutes of Health (NIH)-AARP Diet and Health Study.
AB  - BACKGROUND: Few studies have examined the relationship of lifestyle factors with
      mortality among patients with colorectal cancer. METHODS: Among NIH-AARP Diet and
      Health study participants, 4213 colon and 1514 rectal cancer cases were
      identified through linkage to state cancer registries and determined date and
      cause of death using the National Death Index. Lifestyle factors were assessed at
      baseline and included: healthy diet (measured by Healthy Eating Index 2005 [HEI
      2005]), body mass index (BMI), physical activity, alcohol consumption and
      smoking. The association of factors was examined individually and combined into a
      lifestyle score with 5-year mortality from all-causes, colorectal cancer, and
      cardiovascular disease (CVD). Relative risks (RRs) and 95% confidence intervals
      (CIs) were estimated using Cox proportional hazards models. RESULTS: Among colon
      cancer survivors, smokers had increased risk of total mortality (RR = 1.74; 95%
      CI = 1.45-2.08) and colorectal cancer mortality (RR = 1.46; 95% CI = 1.17-1.82),
      compared to never smokers. Obese (BMI, >= 30) individuals had increased risk of
      all death (RR = 1.19; 95% CI = 1.02-1.39) and CVD death (RR = 1.84; 95% CI = 1.05
      3.23), compared to normal weight (BMI, 18.5 to < 25) individuals. Compared to
      those with the lowest lifestyle score, those with the highest score had a 34%
      lower risk of all-cause mortality (RR = 0.66; 95% CI = 0.50-0.87). Among rectal
      cancer survivors, individuals in the highest quintile of HEI-2005 scores had
      reduced all-cause mortality (RR = 0.60; 95% CI = 0.42-0.86) compared to those in
      the lowest. Higher combined lifestyle scores were associated with a 46% lower
      risk of total mortality (0.54; 0.32-0.91). CONCLUSIONS: Healthier lifestyle
      before cancer diagnosis was associated with improved overall survival after
      diagnosis with colorectal cancer.

PMID- 24591064
TI  - Implementation intention and action planning interventions in health contexts:
      state of the research and proposals for the way forward.
AB  - The purpose of this paper is to provide an overview of the literature on two
      planning intervention techniques in health behaviour research, implementation
      intentions and action planning, and to develop evidence-based recommendations for
      effective future interventions and highlight priority areas for future research.
      We focused our review on four key areas: (1) definition and conceptualisation;
      (2) format and measurement; (3) mechanisms and processes; and (4) design issues.
      Overall, evidence supports the effectiveness of planning interventions in health
      behaviour with advantages including low cost and response burden. There is,
      however, considerable heterogeneity in the effects across studies and relatively
      few registered randomised trials that include objective behavioural measures.
      Optimally effective planning interventions should adopt "if-then" plans, account
      for salient and relevant cues, include examples of cues, be guided rather than
      user-defined, and include boosters. Future studies should adopt randomised
      controlled designs, report study protocols, include fidelity checks and relevant
      comparison groups, and adopt long-term behavioural follow-up measures. Priority
      areas for future research include the identification of the moderators and
      mediators of planning intervention effects. Future research also needs to adopt
      "best practice" components of planning interventions more consistently to
      elucidate the mechanisms and processes involved. 

PMID- 24591063
TI  - Efficacy of different sequences of radio- and chemotherapy in experimental models
      of human melanoma.
AB  - Although combination chemotherapy and radiotherapy have become the standard of
      care in numerous tumors, the mechanisms of interaction are often still unclear.
      The purpose of this study was to analyze the efficacy of radiation treatment and
      cisplatin sequences and to investigate their mechanisms of interaction. Three
      melanoma cell lines were used to evaluate in vitro radiation-induced cytotoxicity
      before and after cisplatin treatment. Expression levels of a panel of genes were
      determined by real-time RT-PCR. Cytotoxic effect was evaluated by flow cytometry
      analysis and Comet assay. We also used normal human dermal fibroblasts (HUDE) to
      evaluate the cytotoxicity of the two treatments by clonogenic assay. Radiation
      and cisplatin used singly were not particularly effective in reducing
      proliferation in melanoma cells. Conversely, radiation treatment followed by
      cisplatin showed a strong synergistic interaction in all cell lines, with a ratio
      index ranging from 16 to >100. The synergistic effect was accompanied by
      apoptosis induction (up to 40%) and an increase in the percentage of comet-shaped
      nucleoids from 85% to 99%. In parallel, our results also showed that radiation
      treatment of HUDE fibroblasts followed by cisplatin only induced weak
      cytotoxicity. Our findings highlight the efficacy of the sequence radiation ->
      cisplatin in reducing cell proliferation and in inducing apoptosis in melanoma
      cell lines. This sequence also modulated a network of proteins involved in DNA
      damage repair.

PMID- 24591065
TI  - Computer-tailored interventions to facilitate health behavioural change.

PMID- 24591066
TI  - Self-assembled metal-organic frameworks crystals for chemical vapor sensing.
AB  - A 3D metal-organic frameworks (MOFs) crystals film is obtained via Langmuir
      Blodgett technique and used as a photonic sensor for chemical vapor detection.
      The MOFs crystals film exhibits both acute responses towards various chemical
      vapors and high controllability in terms of peak intensity and position. The
      method represents a general, facile and flexible strategy for the fabrication of
      MOFs-based photonic sensors. 

PMID- 24591076
TI  - Microfluidic electrophoretic mobility shift assays for quantitative biochemical
      analysis.
AB  - Electrophoretic mobility shift assays (EMSAs) play an important role in
      analytical chemistry, quantitative bioscience, and point-of-care diagnostics.
      Emerging microfluidic lab-on-a-chip technologies bring high throughput and
      multiplexed analysis to affinity-based electrophoretic separations, greatly
      advancing the performance of traditional EMSAs. This review elaborates on the
      relevant theoretical basis for EMSAs, surveys microfluidic-based EMSA
      applications in molecular conformation analyses, immunoassays, affinity assays
      and genomics, and outlines challenges and potential future improvements needed
      from this powerful assay. 

PMID- 24591077
TI  - Mechanisms and effects of "fat taste" in humans.
AB  - Evidence supporting a "taste" cue from fat in the oral cavity continues to
      accrue. The proposed stimuli for fat taste, non-esterified fatty acids (NEFA),
      are released from food through hydrolytic rancidity and lipase activity derived
      from foods or saliva. NEFA must then be released from the food matrix, negotiate
      the aqueous environment to reach taste cell surfaces, and interact with receptors
      such as CD36 and GPR120 or diffuse across cell membranes to initiate a taste
      signal. Knowledge of these processes in non-gustatory tissues should inform
      understanding of taste responses to NEFA. Additionally, downstream effects of
      oral triglyceride exposure have been observed in numerous studies. Data specific
      to effects of NEFA versus triglyceride are scarce, but modified sham feeding
      trials with triglyceride document cephalic phase responses including elevations
      in serum lipids and insulin as well as potential, but debated, effects on gut
      peptides, appetite, and thermogenesis. In this review, we highlight the
      mechanisms by which NEFA migrate to and interact with taste cells, and then we
      examine physiological responses to oral fat exposure.

PMID- 24591080
TI  - Current trends for the use of androgen deprivation therapy in conjunction with
      radiotherapy for patients with unfavorable intermediate-risk, high-risk,
      localized, and locally advanced prostate cancer.
AB  - Androgen deprivation therapy (ADT) is now a well-established standard of care in
      combination with definitive radiotherapy for patients with unfavorable
      intermediate-risk to high-risk locally advanced prostate cancer. It is also well
      established that combination modality treatment with ADT and radiotherapy is
      superior to either of these modalities alone for the treatment of patients with
      high-risk locally advanced disease. Current treatment guidelines for prostate
      cancer in the United States are based on the estimated risk of recurrence and
      death. This review examines the clinical evidence underpinning the use of ADT and
      radiotherapy among patients with high-risk localized and locally advanced disease
      in the United States. This review also considers the rationale for moving from
      traditional luteinizing hormone-releasing hormone agonists to more recently
      developed gonadotrophin-releasing hormone antagonists.

PMID- 24591078
TI  - KCNT1 gain of function in 2 epilepsy phenotypes is reversed by quinidine.
AB  - OBJECTIVE: Mutations in KCNT1 have been implicated in autosomal dominant
      nocturnal frontal lobe epilepsy (ADNFLE) and epilepsy of infancy with migrating
      focal seizures (EIMFS). More recently, a whole exome sequencing study of
      epileptic encephalopathies identified an additional de novo mutation in 1 proband
      with EIMFS. We aim to investigate the electrophysiological and pharmacological
      characteristics of hKCNT1 mutations and examine developmental expression levels.
      METHODS: Here we use a Xenopus laevis oocyte-based automated 2-electrode voltage
      clamp assay. The effects of quinidine (100 and 300 MUM) are also tested. Using
      quantitative reverse transcriptase polymerase chain reaction, the relative levels
      of mouse brain mKcnt1 mRNA expression are determined. RESULTS: We demonstrate
      that KCNT1 mutations implicated in epilepsy cause a marked increase in function.
      Importantly, there is a significant group difference in gain of function between
      mutations associated with ADNFLE and EIMFS. Finally, exposure to quinidine
      significantly reduces this gain of function for all mutations studied.
      INTERPRETATION: These results establish direction for a targeted therapy and
      potentially exemplify a translational paradigm for in vitro studies informing
      novel therapies in a neuropsychiatric disease.

PMID- 24591081
TI  - Genome-wide copy number scan identifies disruption of PCDH11X in developmental
      dyslexia.
AB  - Developmental dyslexia (DD) is a complex heritable disorder with unexpected
      difficulty in learning to read and spell despite adequate intelligence,
      education, environment, and normal senses. We performed a whole genome copy
      number variations (CNV) scan on 11 dyslexic families consisting of 14 dyslexic
      subjects and 24 non dyslexic members using 1.8 million combined SNP and CNV
      markers. We found CNVs affecting protocadherin genes in six dyslexics from three
      families, while none among the non-dyslexic control members showed any CNV in
      protocadherins. We identified duplications in five cases and a deletion in one
      case in Xq21.3 region bearing PCDH11X. Unequal recombination between the X
      transposed region (XTR) of Yp11.2 and the X chromosome might be causing these
      structural changes. PCDH11X, expressed in brain is implicated in cell-cell
      communication, verbal ability, cerebral asymmetry, and dendritic synaptic
      plasticity, may be regarded as a new candidate gene for dyslexia.

PMID- 24591082
TI  - Stabilization of a diphosphagermylene through ppi-ppi interactions with a
      trigonal-planar phosphorus center.
AB  - N-Heterocyclic carbenes and their heavier homologues are, in part, stabilized by
      delocalization of the N lone pairs into the vacant p-orbital at carbon (or a
      heavier Group 14 element center). These interactions are usually absent in the
      corresponding P-substituted species, owing to the large barrier to planarization
      of phosphorus. However, judicious selection of the substituents at phosphorus has
      enabled the synthesis of a diphosphagermylene, [(Dipp)2P]2 Ge, in which one of
      the P centers is planar (Dipp=2,6-diisopropylphenyl). The planar nature of this P
      center and the correspondingly short P-Ge distance suggest a significant degree
      of P-Ge multiple bond character that is due to delocalization of the phosphorus
      lone pair into the vacant p-orbital at germanium. DFT calculations support this
      proposition and NBO and AIM analyses are consistent with a Ge-P bond order
      greater than unity.

PMID- 24591083
TI  - 25th anniversary article: carbon nanotube- and graphene-based transparent
      conductive films for optoelectronic devices.
AB  - Carbon nanotube (CNT)- and graphene (G)-based transparent conductive films (TCFs)
      are two promising alternatives for commonly-used indium tin oxide-based TCFs for
      future flexible optoelectronic devices. This review comprehensively summarizes
      recent progress in the fabrication, properties, modification, patterning, and
      integration of CNT- and G-TCFs into optoelectronic devices. Their potential
      applications and challenges in optoelectronic devices, such as organic
      photovoltaic cells, organic light emitting diodes and touch panels, are discussed
      in detail. More importantly, their key characteristics and advantages for use in
      these devices are compared. Despite many challenges, CNT- and G-TCFs have
      demonstrated great potential in various optoelectronic devices and have already
      been used for some products like touch panels of smartphones. This illustrates
      the significant opportunities for the industrial use of CNTs and graphene, and
      hence pushes nanoscience and nanotechnology one step towards practical
      applications. 

PMID- 24591084
TI  - Clinical outcomes of carbon ion radiotherapy for locally advanced adenocarcinoma
      of the uterine cervix in phase 1/2 clinical trial (protocol 9704).
AB  - BACKGROUND: This study sought to evaluate the toxicity and efficacy of carbon ion
      radiotherapy (C-ion RT) for locally advanced adenocarcinoma of the uterine cervix
      in a phase 1/2 clinical trial. METHODS: The treatment consisted of whole-pelvic
      irradiation of 36.0 gray equivalents (GyE) in 12 fractions and local boost with
      dose escalation from 26.4 to 38.4 GyE in 8 fractions. The dose escalation was
      performed with careful observation of acute normal tissue responses. Total dose
      to the cervical tumor was 62.4 to 74.4 GyE in 20 fractions. RESULTS: Between
      April 1998 and February 2010, 58 patients were treated with C-ion RT in this
      clinical trial. The number of patients with stage IIB, IIIB, and IVA disease were
      20, 35, and 3, respectively. Median tumor size was 5.5 cm (range, 3.0-11.8 cm).
      Twenty-seven patients had pelvic lymph node metastases. The median follow-up
      period was 38 months. All patients completed the treatment schedule. Grade 2 or
      higher late toxicity was found in 8 patients: 5 with bladder and 2 with small
      intestine grade 2 toxicities, and 1 patient had grade 4 rectal complication,
      which was surgically salvaged. The 5-year local control rate, local control rate
      including salvage surgery, and overall survival rate in all cases were 54.5%,
      68.2%, and 38.1%, respectively. CONCLUSIONS: Dose escalation of C-ion RT for
      adenocarcinoma of the uterine cervix was accomplished without severe toxicities
      except in 1 case. Although the number of patients in this study was small, the
      results support continued investigation and analysis to confirm therapeutic
      efficacy.

PMID- 24591085
TI  - MicroRNA-155 and microRNA-196b: promising biomarkers in hepatitis C virus
      infection?
AB  - MicroRNAs (miRNAs) are a class of small, evolutionarily conserved, noncoding RNA
      that regulate several important cellular processes. The versatility of these
      molecules allowed the accurate predictions that they would also affect the
      replication and life cycle of HCV. In this review, emphasis has been given to two
      selected miRNAs: miR-155 and miR-196b. Recent data indicate that miR-155 is
      overexpressed in HCV-infected patients, inducing an inflammatory state, and
      promoting virus replication and persistence even after the completion of
      antiviral treatment. It is also associated with the increased proliferation and
      inhibited apoptosis of hepatocytes, which promotes the growth of liver tumors. In
      contrast, miR-196b is reported as a factor inhibiting HCV replication with
      cytoprotective, anti-inflammatory, and antioxidant properties. Growing evidence
      suggests that these molecules could be used as potential prognostic and
      predictive factors and their antagonists or mimics as a promising therapeutic
      approach in HCV-infected patients.

PMID- 24591090
TI  - Characterization of olive mill wastewater fractions treatment by integrated
      membrane process.
AB  - BACKGROUND: Up to now, the management of olive mill wastewaters, a three-phase
      mill by-product, remains an unsolved problem, in particular for those regions
      where huge quantities of vegetable water are produced. Olive mill wastewaters
      were therefore treated to evaluate the characteristics of permeate and retentate
      fractions produced by an integrated membrane system working at two different
      volume concentration factors. RESULTS: The effect of two membrane-based
      filtration steps (microfiltration and nanofiltration) on the content of chemical
      oxygen demand, dry matter, sensory quality, phenolic compounds and antioxidant
      activity of permeate and retentate samples was evaluated. Furthermore, the effect
      of two different volume concentration factors (VCF), in the nanofiltration step,
      were investigated. At high VCF values, the total phenolic content in the
      retentate fraction was found to be 3.7-fold higher than the starting one, while
      the reduction of chemical oxygen demand in the permeate fraction was greater than
      97% also at lower VCF values. CONCLUSION: Each filtration step has provided
      useful information concerning the utility and appropriateness of the processes
      chosen, suggesting a sustainable hypothesis of 'normal industrial practice' that
      can be included in current processes of oil extraction, in order to purify water
      and recover phenolic compounds with high added value.

PMID- 24591091
TI  - Understanding electrogenerated chemiluminescence efficiency in blue-shifted
      iridium(III)-complexes: an experimental and theoretical study.
AB  - Compared to tris(2-phenylpyridine)iridium(III) ([Ir(ppy)3 ]), iridium(III)
      complexes containing difluorophenylpyridine (df-ppy) and/or an ancillary
      triazolylpyridine ligand [3-phenyl-1,2,4-triazol-5-ylpyridinato (ptp) or 1-benzyl
      1,2,3-triazol-4-ylpyridine (ptb)] exhibit considerable hypsochromic shifts (ca.
      25-60 nm), due to the significant stabilising effect of these ligands on the HOMO
      energy, whilst having relatively little effect on the LUMO. Despite their lower
      photoluminescence quantum yields compared with [Ir(ppy)3 ] and [Ir(df-ppy)3 ],
      the iridium(III) complexes containing triazolylpyridine ligands gave greater
      electrogenerated chemiluminescence (ECL) intensities (using tri-n-propylamine
      (TPA) as a co-reactant), which can in part be ascribed to the more energetically
      favourable reactions of the oxidised complex (M(+) ) with both TPA and its
      neutral radical oxidation product. The calculated iridium(III) complex LUMO
      energies were shown to be a good predictor of the corresponding M(+) LUMO
      energies, and both HOMO and LUMO levels are related to ECL efficiency. The
      theoretical and experimental data together show that the best strategy for the
      design of efficient new blue-shifted electrochemiluminophores is to aim to
      stabilise the HOMO, while only moderately stabilising the LUMO, thereby
      increasing the energy gap but ensuring favourable thermodynamics and kinetics for
      the ECL reaction. Of the iridium(III) complexes examined, [Ir(df-ppy)2 (ptb)](+)
      was most attractive as a blue-emitter for ECL detection, featuring a large
      hypsochromic shift (lambdamax =454 and 484 nm), superior co-reactant ECL
      intensity than the archetypal homoleptic green and blue emitters: [Ir(ppy)3 ] and
      [Ir(df-ppy)3 ] (by over 16-fold and threefold, respectively), and greater
      solubility in polar solvents. 

PMID- 24591092
TI  - Low-dose lamotrigine augmentation therapy improves residual symptoms in treatment
      resistant schizophrenia: a report of five cases.
AB  - INTRODUCTION: Treatment-resistant schizophrenia (TRS) refers to the approximately
      20-30% of schizophrenia patients whose symptoms are resistant to any
      antipsychotic treatment. For the improvement of residual symptoms in TRS,
      augmentation therapy using anticonvulsants such as lamotrigine (LTG) has recently
      attracted attention. Randomized clinical trials (RCTs) have demonstrated robust
      evidence; however, the results have shown both positive and negative outcomes for
      the use of LTG. Although RCTs have merit, they also obscure informative clinical
      features present in each patient, such as the types of TRS that show the most
      significant effects from LTG. Thus, detailed case reports examining the efficacy
      of LTG may help to shed light on various treatments for complex, heterogeneous
      diseases such as schizophrenia. METHODS: We present detailed reports on the
      clinical course and features of TRS in five patients suffering from severe
      positive symptoms who were treated with LTG augmentation therapy. RESULTS: After
      the administration of LTG augmentation therapy, two patients did not show any
      improvement in their residual symptoms, while the remaining three patients did
      experience improvement. Remarkably, patients with more severe residual positive
      symptoms, especially those with auditory hallucinations, seemed to respond better
      to low-dose LTG (50 mg daily). Additional clinical variables, such as type and
      dose of ongoing antipsychotics, age of onset, duration of illness, duration of
      untreated psychosis, number of administration cycles, and genetic heritability,
      were not found to be related to the effectiveness of LTG augmentation.
      DISCUSSION: Low-dose LTG augmentation therapy seems to improve residual symptoms
      in some cases of TRS. The glutamatergic properties of LTG may be the decisive
      factor in these symptoms, as other glutamatergic agents have also been shown to
      be effective based on previous glutamate hypotheses in schizophrenia.

PMID- 24591093
TI  - Asian paradox of psychological support: findings from the second Diabetes
      Attitudes Wishes and Needs study (DAWN-2).

PMID- 24591094
TI  - Prediction of therapeutic responses to tocilizumab in patients with rheumatoid
      arthritis: biomarkers identified by analysis of gene expression in peripheral
      blood mononuclear cells using genome-wide DNA microarray.
AB  - OBJECTIVE: The aim of this prospective multicenter study was to identify
      biomarkers that can be used to predict therapeutic responses to tocilizumab in
      patients with rheumatoid arthritis (RA). METHODS: We recruited patients with RA
      who were treated with tocilizumab for the first time, and determined therapeutic
      responses at 6 months. In the training cohort (n = 40), gene expression in
      peripheral blood mononuclear cells (PBMCs) at baseline was analyzed using genome
      wide DNA microarray, with 41,000 probes derived from 19,416 genes. In the
      validation cohort (n = 20), expression levels of the candidate genes in PBMCs at
      baseline were determined using real-time quantitative polymerase chain reaction
      (qPCR) analysis. RESULTS: We identified 68 DNA microarray probes that showed
      significant differences in signal intensity between nonresponders and responders
      in the training cohort. Nineteen putative genes were selected, and a significant
      correlation between the DNA microarray signal intensity and the qPCR relative
      expression was confirmed in 15 genes. In the validation cohort, a significant
      difference in relative expression between nonresponders and responders was
      reproduced for 3 type I interferon response genes (IFI6, MX2, and OASL) and MT1G.
      Receiver operating characteristic curve analysis of models incorporating these
      genes showed that the maximum area under the curve was 0.947 in predicting a
      moderate or good response to tocilizumab in the validation cohort. CONCLUSION:
      Using genome-wide DNA microarray analyses, we identified candidate biomarkers
      that can be used to predict therapeutic responses to tocilizumab in patients with
      RA. These findings suggest that type I interferon signaling and metallothioneins
      are involved in the pathophysiology of RA.

PMID- 24591095
TI  - Glucosamine-induced Sp1 O-GlcNAcylation ameliorates hypoxia-induced SGLT
      dysfunction in primary cultured renal proximal tubule cells.
AB  - The aim of this study is to determine whether GlcN could recover the endoplasmic
      reticulum (ER) stress-induced dysfunction of Na(+) /glucose cotransporter (SGLT)
      in renal proximal tubule cells (PTCs) under hypoxia. With the rabbit model, the
      renal ischemia induced tubulointerstitial abnormalities and decreased SGLTs
      expression in tubular brush-border, which were recovered by GlcN. Thus, the
      protective mechanism of GlcN against renal ischemia was being examined by using
      PTCs. Hypoxia decreased the level of protein O-GlcNAc and the expression of O
      GlcNAc transferase (OGT) while increased O-GlcNAcase (OGA) and these were
      reversed by GlcN. Hypoxia also decreased the expression of SGLTs (SGLT1 and 2)
      and [(14) C]-alpha-methyl-D-glucopyranoside (alpha-MG) uptake which were
      recovered by GlcN and PUGNAc (OGA inhibitor). Hypoxia enhanced reactive oxygen
      species (ROS) and then ER stress proteins, glucose-regulated protein 78 (GRP78),
      and C/EBP-homologous protein (CHOP). However, the expression of GRP78 increased
      till 6 h and then decreased whereas CHOP increased gradually. Moreover, decreased
      GRP78 and increased CHOP were reversed by NAC (antioxidant) and GlcN. GlcN
      ameliorated hypoxia-induced decrease of O-GlcNAc modification of Sp1 but OGT or
      Sp1 siRNAs blocked the recovery effect of GlcN on SGLT expression and alpha-MG
      uptake. In addition, hypoxia-decreased GRP78 and HIF-1alpha expression was
      reversed by GlcN but OGT siRNA or Sp1 siRNA ameliorated the effect of GlcN. When
      PTCs were transfected with GRP78 siRNA or HIF-1alpha siRNA, SGLT expression and
      alpha-MG uptake was decreased. Taken together, these data suggest that GlcN
      induced O-GlcNAc modified Sp1 with stimulating GRP78 and HIF-1alpha activity
      ameliorate hypoxia-induced SGLT dysfunction in renal PTCs. J. Cell. Physiol. 229:
      1557-1568, 2014. (c) 2014 Wiley Periodicals, Inc. 

PMID- 24591096
TI  - Inhibition of cathepsin K increases modeling-based bone formation, and improves
      cortical dimension and strength in adult ovariectomized monkeys.
AB  - Treatment with the cathepsin K (CatK) inhibitor odanacatib (ODN) protects against
      bone loss and maintains normal biomechanical properties in the spine and hip of
      ovariectomized (OVX) preclinical models. Here, we characterized the effects of
      ODN on the dynamics of cortical modeling and remodeling, and dimension and
      strength of the central femur in adult OVX-rhesus monkeys. Animals were treated
      with vehicle or ODN (6 or 30 mg/kg, once per day [q.d., p.o.]) in prevention mode
      for 21 months. Calcein and tetracycline double-labeling were given at 12 and 21
      months, and the femoral cross-sections were subjected to dynamic
      histomorphometric and cement line analyses. ODN treatment significantly increased
      periosteal and endocortical bone formation (BFR/BS), accompanied with an increase
      in endocortical mineralizing surface (102%, p < 0.01) with the 6 mg/kg dose. ODN
      at both doses reduced remodeling hemiosteon numbers by 51% and 66% (p < 0.05),
      respectively, and ODN 30 mg/kg numerically reduced activation frequency without
      affecting wall thickness. On the same endocortical surface, ODN increased all
      modeling-based parameters, while reducing intracortical remodeling, consistent
      with the observed no treatment effects on cortical porosity. ODN 30 mg/kg
      markedly increased cortical thickness (CtTh, p < 0.001) and reduced marrow area
      (p < 0.01). Lastly, ODN treatment increased femoral structural strength (p <
      0.001). Peak load was positively correlated with the increases in bone mineral
      content (BMC) (r(2)  = 0.9057, p < 0.0001) and CtTh (r2  = 0.6866, p < 0.0001).
      Taken together, by reducing cortical remodeling-based and stimulating modeling
      based bone formation, ODN significantly improved cortical dimension and strength
      in OVX monkeys. This novel mechanism of CatK inhibition in stimulating cortical
      formation suggests that ODN represents a novel therapeutic approach for the
      treatment of osteoporosis.

PMID- 24591098
TI  - Ordered 2D colloidal photonic crystals on gold substrates by surfactant-assisted
      fast-rate dip coating.

PMID- 24591097
TI  - Lefetamine-derived designer drugs N-ethyl-1,2-diphenylethylamine (NEDPA) and N
      iso-propyl-1,2-diphenylethylamine (NPDPA): metabolism and detectability in rat
      urine using GC-MS, LC-MSn and LC-HR-MS/MS.
AB  - N-Ethyl-1,2-diphenylethylamine (NEDPA) and N-iso-propyl-1,2-diphenylethylamine
      (NPDPA) are two designer drugs, which were confiscated in Germany in 2008.
      Lefetamine (N,N-dimethyl-1,2-diphenylethylamine, also named L-SPA), the
      pharmaceutical lead of these designer drugs, is a controlled substance in many
      countries. The aim of the present work was to study the phase I and phase II
      metabolism of these drugs in rats and to check for their detectability in urine
      using the authors' standard urine screening approaches (SUSA). For the
      elucidation of the metabolism, rat urine samples were worked up with and without
      enzymatic cleavage, separated and analyzed by gas chromatography-mass
      spectrometry (GC-MS) and liquid chromatography-high resolution-tandem mass
      spectrometry (LC-HR-MS/MS). According to the identified metabolites, the
      following metabolic pathways for NEDPA and NPDPA could be proposed: N
      dealkylation, mono- and bis-hydroxylation of the benzyl ring followed by
      methylation of one of the two hydroxy groups, combinations of these steps,
      hydroxylation of the phenyl ring after N-dealkylation, glucuronidation and
      sulfation of all hydroxylated metabolites. Application of a 0.3 mg/kg BW dose of
      NEDPA or NPDPA, corresponding to a common lefetamine single dose, could be
      monitored in rat urine using the authors' GC-MS and LC-MS(n) SUSA. However, only
      the metabolites could be detected, namely N-deethyl-NEDPA, N-deethyl-hydroxy
      NEDPA, hydroxy-NEDPA, and hydroxy-methoxy-NEDPA or N-de-iso-propyl-NPDPA, N-de
      iso-propyl-hydroxy-NPDPA, and hydroxy-NPDPA. Assuming similar kinetics, an intake
      of these drugs should also be detectable in human urine.

PMID- 24591099
TI  - The search for peripheral biomarkers for major depression: benefiting from
      successes in the biology of smoking.
AB  - The search for robust, clinically useful markers for major depression (MD) has
      been relatively unproductive. This is unfortunate because MD is one of the
      largest socio-economic challenges for much of the world and the development of
      reliable biomarkers for MD could aid in the prevention or treatment of this
      common syndrome. In this editorial, we compare the approaches taken in the search
      for biomarkers for MD to that of the more successful searches for biomarkers for
      tobacco use, and identify several substantive barriers. We suggest that many of
      the existing clinical repositories used in these biomarkers searches for MD may
      be of limited value. We conclude that in the future greater attention should be
      given to the clinical definitions, characterization of confounding environmental
      factors and age of subjects included in studies. (c) 2014 Wiley Periodicals, Inc.

PMID- 24591100
TI  - o-Carborane-based biphenyl and p-terphenyl derivatives.
AB  - The synthesis and properties of biphenyl- and p-terphenyl-fused o-carboranes are
      described. Aryl rings in the biphenyl and p-terphenyl skeletons are highly
      coplanar because of the presence of the o-carborane unit. o-Carborane exhibits an
      electron-withdrawing character via the inductive effect, resulting in a decrease
      in both the HOMO and LUMO levels of oligophenyls without causing electronic
      perturbation. 

PMID- 24591101
TI  - Reply: To PMID 24519039.

PMID- 24591102
TI  - Evolution of iron(II)-finger peptides by using a bipyridyl amino acid.
AB  - We report the engineering of zinc-finger-like motifs containing the unnatural
      amino acid (2,2'-bipyridin-5-yl)alanine (Bpy-Ala). A phage-display library was
      constructed in which five residues in the N-terminal finger of zif268 were
      randomized to include both canonical amino acids and Bpy-Ala. Panning of this
      library against a nine-base-pair DNA binding site identified several Bpy-Ala
      containing functional Zif268 mutants. These mutants bind the Zif268 recognition
      site with affinities comparable to that of the wild-type protein. Further
      characterization indicated that the mutant fingers bind low-spin Fe(II) rather
      than Zn(II) . This work demonstrates that an expanded genetic code can lead to
      new metal ion binding motifs that can serve as structural, catalytic, or
      regulatory elements in proteins. 

PMID- 24591103
TI  - Genetic structure of little brown bats (Myotis lucifugus) corresponds with spread
      of white-nose syndrome among hibernacula.
AB  - Until recently, the little brown bat (Myotis lucifugus) was one of the most
      common bat species in North America. However, this species currently faces a
      significant threat from the emerging fungal disease white-nose syndrome (WNS).
      The aims of this study were to examine the population genetic structure of M.
      lucifugus hibernating colonies in Pennsylvania (PA) and West Virginia (WV), and
      to determine whether that population structure may have influenced the pattern of
      spread of WNS. Samples were obtained from 198 individuals from both uninfected
      and recently infected colonies located at the crest of the disease front. Both
      mitochondrial (636bp of cytochrome oxidase I) and nuclear (8 microsatellites)
      loci were examined. Although no substructure was evident from nuclear DNA, female
      mediated gene flow was restricted between hibernacula in western PA and the
      remaining colonies in eastern and central PA and WV. This mitochondrial genetic
      structure mirrors topographic variation across the region: 3 hibernating colonies
      located on the western Appalachian plateau were significantly differentiated from
      colonies located in the central mountainous and eastern lowland regions,
      suggesting reduced gene flow between these clusters of colonies. Consistent with
      the hypothesis that WNS is transmitted primarily through bat-to-bat contact,
      these same 3 hibernating colonies in westernmost PA remained WNS-free for 1-2
      years after the disease had swept through the rest of the state, suggesting that
      female migration patterns may influence the spread of WNS across the landscape.

PMID- 24591104
TI  - A novel mechanism for cyclic adenosine monophosphate-mediated memory formation:
      Role of amyloid beta.
AB  - Cyclic adenosine monophosphate (cAMP) regulates long-term potentiation (LTP) and
      ameliorates memory in healthy and diseased brain. Increasing evidence shows that,
      under physiological conditions, low concentrations of amyloid beta (Abeta) are
      necessary for LTP expression and memory formation. Here, we report that cAMP
      controls amyloid precursor protein (APP) translation and Abeta levels, and that
      the modulatory effects of cAMP on LTP occur through the stimulation of APP
      synthesis and Abeta production.

PMID- 24591105
TI  - Equalizer technology followed by DIGE-based proteomics for detection of cellular
      proteins in artificial peritoneal dialysis effluents.
AB  - Peritoneal dialysis effluent (PDE) represents a rich pool of potential biomarkers
      for monitoring disease and therapy. Until now, proteomic studies have been
      hindered by the plasma-like composition of the PDE. Beads covered with a peptide
      library are a promising approach to remove high abundant proteins and concentrate
      the sample in one step. In this study, a novel approach for proteomic biomarker
      identification in PDEs consisting of a depletion and concentration step followed
      by 2D gel based protein quantification was established. To prove this
      experimental concept a model system of artificial PDEs was established by spiking
      unused peritoneal dialysis (PD) fluids with cellular proteins reflecting control
      conditions or cell stress. Using this procedure, we were able to reduce the
      amount of high abundant plasma proteins and concentrate low abundant proteins
      while preserving changes in abundance of proteins with cellular origin. The
      alterations in abundance of the investigated marker for cell stress, the heat
      shock proteins, showed similar abundance profiles in the artificial PDE as in
      pure cell culture samples. Our results demonstrate the efficacy of this system in
      detecting subtle changes in cellular protein expression triggered by
      unphysiological stress stimuli typical in PD, which could serve as biomarkers.
      Further studies using patients' PDE will be necessary to prove the concept in
      clinical PD and to assess whether this technique is also informative regarding
      enriching low abundant plasma derived protein biomarker in the PDE. 

PMID- 24591106
TI  - MRI and MRA of spinal cord arteriovenous shunts.
AB  - The purpose of this review is to describe the diagnostic criteria for spinal cord
      arteriovenous shunts (SCAVSs) when using magnetic resonance imaging (MRI) and
      magnetic resonance angiography (MRA), and to discuss the extent to which the
      different MRI and MRA sequences and technical parameters provide the information
      that is required to diagnose these lesions properly. SCAVSs are divided into four
      groups according to location (paraspinal, epidural, dural, or intradural) and
      type (fistula or nidus); each type of lesion is described. SCAVSs are responsible
      for neurological symptoms due to spinal cord or nerve root involvement. MRI is
      usually the first examination performed when a spinal cord lesion is suspected.
      Recognition of the image characteristics of vascular lesions is mandatory if
      useful sequences are to be performed-especially MRA sequences. Because the
      treatment of SCAVSs relies mainly on endovascular therapies, MRI and MRA help
      with the planning of the angiographic procedure. We explain the choice of MRA
      sequences and parameters, the advantages and pitfalls to be aware of in order to
      obtain the best visualization, and the analysis of each lesion.

PMID- 24591107
TI  - Nerium indicum, a botanical pesticide affects ultimobranchial gland of the
      catfish Heteropneustes fossilis.
AB  - Heteropneustes fossilis were subjected to 11.27 mg L(-1) (80% of 96 h LC50 ) and
      2.81 mg L(-1) (20% of 96 h LC50 ) of Nerium indicum leaf extract for short-term
      and long-term, respectively. After sacrificing the fish, blood was collected on
      24, 48, 72, and 96 h in short-term and after 7, 14, 21, and 28 days in long-term
      experiment and analyzed for plasma calcium levels. Also, ultimobranchial glands
      (UBG) were fixed on these intervals. Serum calcium levels of H. fossilis
      exhibited a decline after 48 h following exposure to Nerium indicum leaf extract.
      This decrease continued till the end of the experiment (96 h). Ultimobranchial
      cells exhibited a decrease in the cytoplasmic staining response after 72 h
      following the treatment. The nuclear volumes of these cells were slightly
      decreased. These changes were exaggerated after 96 h following the treatment.
      Chronically exposed fish exhibited a decline in serum calcium levels of H.
      fossilis on day 14. The level progressively declined till the end of the
      experiment. Up to day 14 following the treatment there was no change in the
      histological structure of UBG. A decrease in the nuclear volume of
      ultimobranchial cells was noticed on day 21. Moreover, the cytoplasm of these
      cells displayed weakstaining response. The nuclear volume of these cells recorded
      a further decrease following 28-day treatment. Also there was noticed
      vacuolization and degeneration at certain places. To the best of our knowledge,
      the effects of any botanical pesticides on fish UBG have not been reported yet.

PMID- 24591108
TI  - The antioxidant effects of pumpkin seed oil on subacute aflatoxin poisoning in
      mice.
AB  - This study was aimed at the investigation of the antioxidant effect of pumpkin
      seed oil against the oxidative stress-inducing potential of aflatoxin. For this
      purpose, 48 male BALB/c mice were used. Four groups, each comprising 12 mice,
      were established. Group 1 was maintained as the control group. Group 2 was
      administered with pumpkin seed oil alone at a dose of 1.5 mL/kg.bw/day
      (~1375mg/kg.bw/day). Group 3 received aflatoxin (82.45% AFB1 , 10.65% AFB2 ,
      4.13% AFG1, and 2.77% AFG2 ) alone at a dose of 625 MUg/kg.bw/day. Finally, group
      4 was given both 1.5 mL/kg.bw/day pumpkin seed oil and 625 MUg/kg.bw/day
      aflatoxin. All administrations were oral, performed with the aid of a gastric
      tube and continued for a period of 21 days. At the end of day 21, the liver,
      lungs, kidneys, brain, heart, and spleen of the animals were excised, and the
      extirpated tissues were homogenized appropriately. Malondialdehyde (MDA) levels
      and catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH
      Px) activities were determined in tissue homogenates. In conclusion, it was
      determined that aflatoxin exhibited adverse effects on most of the oxidative
      stress markers. The administration of pumpkin seed oil diminished aflatoxin
      induced adverse effects. In other words, the values of the group, which was
      administered with both aflatoxin and pumpkin seed oil, were observed to have
      drawn closer to the values of the control group.

PMID- 24591110
TI  - Inversion of layer-specific cadherin expression profiles and maintenance of
      cytoarchitectonic areas in the allocortex of the reeler mutant mouse.
AB  - Cadherins are calcium-depending cell adhesion proteins that play critical roles
      in brain morphogenesis and wiring. They provide an adhesive code for the
      development of cortical layers, due to their homophilic interactions and their
      restricted spatiotemporal expression patterns. In the adult organism, cadherins
      are involved in the maintenance and plasticity of neuronal circuits that play a
      role in learning. A well-known model for studying corticogenesis is the reeler
      mouse model. Numerous investigations of neocortical development suggest that, in
      the reeler mutant mouse, the lack of the protein Reelin results in cell-type and
      region-dependent changes of the neocortical layers. To investigate in detail how
      layer formation and regionalization is perturbed in the phylogenetically older
      archicortex of the adult reeler mutant mouse, we studied the expression of 11
      different cadherins (Cdh4, Cdh7, Cdh8, Cdh11, Pcdh1, Pcdh7, Pcdh8, Pcdh9, Pcdh10,
      Pcdh17, and Pcdh19) and of the transcription factors ER81 and Cux2 by in situ
      hybridization in the (peri-)archicortex. All cadherins studied show a layer
      specific expression in the (peri-)archicortex of the wildtype brain. In the
      archicortex of the reeler mutant, the cadherin-expressing cell layers are
      dispersed in the radial dimension, whereas in the periarchicortex the superficial
      and deep layers are inverted, both in the adult and during development. Possibly,
      this inversion relates to the histoarchitectural division of the reeler
      entorhinal cortex into an external and an internal zone. The regionalized,
      gradient-like expression of the cadherins is preserved in the reeler mutant
      mouse.

PMID- 24591109
TI  - Tumor vasculature targeting: a generally applicable approach for functionalized
      nanomaterials.
AB  - The last decade has witnessed an unprecedented expansion in the design, synthesis
      and preclinical applications of various multifunctional nanomaterials. Efficient
      targeting of these nanomaterials to the tumor site is critical for delivering
      sufficient amount of anti-cancer drugs to suppress tumor growth, while avoiding
      undesired side effects. Although some nanoparticles could accumulate in the tumor
      tissue based on the enhanced permeability and retention effect, which may also
      bind to targets on the tumor cell surface after extravasation from the tumor
      vasculature, these strategies have many limitations. In this article, we discuss
      the concept of tumor vasculature targeting and summarize representative examples
      of in vivo targeted positron emission tomography imaging of various
      functionalized nanomaterials with different morphology, size and surface
      chemistry. The concept of targeting tumor vasculature instead of (or in addition
      to) tumor cells will continue to inspire the design of more advanced nanosystems
      for efficacious and personalized treatment of cancer in the future. 

PMID- 24591111
TI  - Start of new year's note.

PMID- 24591112
TI  - Knowing the code.

PMID- 24591113
TI  - Cytometry for immunology: the marriage continues.

PMID- 24591117
TI  - (Gold nanorod core)/(polyaniline shell) plasmonic switches with large plasmon
      shifts and modulation depths.
AB  - (Gold nanorod core)/(polyaniline shell) nanostructures are prepared for
      functioning as active plasmonic switches. The single core/shell nanostructures
      exhibit a remarkable switching performance, with the modulation depth and
      scattering peak shift reaching 10 dB and 100 nm, respectively. The nanostructures
      are also deposited on substrates to form macroscale monolayers with remarkable
      ensemble plasmonic switching performances. 

PMID- 24591118
TI  - The psychological impact of overactive bladder: A systematic review.
AB  - This review aimed to provide an overview of the current research on the
      psychological impact of overactive bladder. A systematic search yielded 32
      papers. It was found that people with overactive bladder tended to have greater
      levels of depression, anxiety and embarrassment/shame; difficulties with social
      life; impact on sleep and sexual relationships; and a lower quality of life than
      people without overactive bladder. A psychological impact on family members was
      also found. Psychological health should be considered an important aspect of
      managing overactive bladder and further research is required to determine how
      best to provide psychological care and support in this area. 

PMID- 24591119
TI  - Adolescent girls' views on cosmetic surgery: A focus group study.
AB  - This study examined adolescent girls' views of cosmetic surgery. Seven focus
      groups were run with girls aged 15-18 years (N = 27). Participants read case
      studies of women having cosmetic surgery, followed by discussion and exploration
      of their views. Thematic analysis identified four themes: (1) dissatisfaction
      with appearance, (2) acceptability of cosmetic surgery, (3) feelings about
      undergoing cosmetic surgery and (4) cosmetic surgery in the media. Results
      suggest the acceptability of cosmetic surgery varies according to the reasons for
      having it and that the media play an important role by normalising surgery and
      under-representing the risks associated with it. 

PMID- 24591120
TI  - Variables associated with patient activation in persons with multiple sclerosis.
AB  - Identifying variables associated with patient activation in the multiple
      sclerosis population could serve to facilitate better multiple sclerosis self
      management behaviors. Using a cross-sectional survey design, 199 participants
      were recruited from a multiple sclerosis center in the Southeastern United
      States. Depression, multiple sclerosis quality of life, and multiple Sclerosis
      self-efficacy were all significantly correlated with patient activation. Results
      of a hierarchical regression indicated that patient activation was significantly
      related to educational attainment, depression, and self-efficacy but not to
      quality of life. The results suggest several possible targets for intervention to
      increase patient activation, including health literacy, depression symptoms, and
      self-efficacy for multiple sclerosis disease management. 

PMID- 24591121
TI  - SiO(2) /TiO(2) hollow nanoparticles decorated with Ag nanoparticles: enhanced
      visible light absorption and improved light scattering in dye-sensitized solar
      cells.
AB  - Hollow SiO2 /TiO2 nanoparticles decorated with Ag nanoparticles (NPs) of
      controlled size (Ag@HNPs) were fabricated in order to enhance visible-light
      absorption and improve light scattering in dye-sensitized solar cells (DSSCs).
      They exhibited localized surface plasmon resonance (LSPR) and the LSPR effects
      were significantly influenced by the size of the Ag NPs. The absorption peak of
      the LSPR band dramatically increased with increasing Ag NP size. The LSPR of the
      large Ag NPs mainly increased the light absorption at short wavelengths, whereas
      the scattering from the SiO2 /TiO2 HNPs improved the light absorption at long
      wavelengths. This enabled the working electrode to use the full solar spectrum.
      Furthermore, the SiO2 layer thickness was adjusted to maximize the LSPR from the
      Ag NPs and avoid corrosion of the Ag NPs by the electrolyte. Importantly, the
      power conversion efficiency (PCE) increased from 7.1 % with purely TiO2 -based
      DSSCs to 8.1 % with HNP-based DSSCs, which is an approximately 12 % enhancement
      and can be attributed to greater light scattering. Furthermore, the PCEs of
      Ag@HNP-based DSSCs were 11 % higher (8.1 vs. 9.0 %) than the bare-HNP-based
      DSSCs, which can be attributed to LSPR. Together, the PCE of Ag@HNP-based DSSCs
      improved by a total of 27 %, from 7.1 to 9.0 %, due to these two effects. This
      comparative research will offer guidance in the design of multifunctional
      nanomaterials and the optimization of solar-cell performance. 

PMID- 24591122
TI  - One-step exfoliation and fluorination of boron nitride nanosheets and a study of
      their magnetic properties.
AB  - A novel, simple, and efficient method for the preparation of the fluorinated
      hexagonal boron nitride nanosheets (F-BNNSs) and the corresponding magnetic
      properties is presented. A one-step route is used to exfoliate and fluorinate the
      BNNSs by ammonium fluoride (NH4F) from hexagonal boron nitride (h-BN) powder.
      Through related instrument characterizations and theoretical calculations, we
      confirm that large-area and few-layer F-BNNSs were successfully produced by this
      method, which can be attributed to a fluorination-assisted exfoliation mechanism
      from the bulk h-BN in NH4F. More intriguingly, we initially verified that the as
      prepared F-BNNSs exhibit ferromagnetic characteristics, which would have good
      potential applications in spintronic devices.

PMID- 24591123
TI  - The risk of systemic lupus erythematosus associated with vaccines: an
      international case-control study.
AB  - OBJECTIVE: Studies have suggested that systemic lupus erythematosus (SLE) may be
      triggered by vaccinations. We undertook this study to investigate the
      relationship between vaccination and onset of SLE. METHODS: This international
      case-control study was conducted between April 2008 and June 2012 in 36
      specialist referral centers (34 in France and 2 in Quebec, Canada) and recruited
      patients <=60 years old recently diagnosed as having either definite SLE (meeting
      >=4 American College of Rheumatology [ACR] criteria including at least 1
      immunologic criterion) or probable SLE (meeting 3 ACR criteria including at least
      1 immunologic criterion). Controls were recruited from general practice settings
      through a closely monitored protocol and matched to patients by age, sex, region
      of residence, and date of recruitment. Vaccinations and other potential risk
      factors for SLE were assessed using a standardized telephone interview. We
      compared proportions of patients and controls who were vaccinated 12 and 24
      months before the index date (date of first clinical symptom presented by the
      patient) using odds ratios (ORs) from conditional logistic regression. RESULTS:
      We assessed 105 patients (89 with definite SLE and 16 with probable SLE) and 712
      controls. Twenty-two of the 105 patients (21.0%) and 181 of the 712 controls
      (25.4%) had received at least 1 vaccination within 24 months before the index
      date (adjusted OR 0.9 [95% confidence interval 0.5-1.5]). The proportions of
      patients and controls vaccinated within the previous 12 months were also similar.
      CONCLUSION: Our study showed no association between exposure to vaccination and
      risk of developing SLE.

PMID- 24591124
TI  - Navigator based respiratory gating during acquisition and preparation phases for
      proton liver spectroscopy at 3 T.
AB  - Proton magnetic resonance spectroscopy ((1)H MRS) enables the non-invasive
      investigation of the human liver; however, because of technical difficulties it
      is not regularly used for diagnosis of liver diseases in clinical routine.
      Breathing motion is one of the major challenges, as it decreases spectral quality
      and leads to misplacement of the spectroscopic voxel. To overcome this problem,
      real-time navigator gating for spectral acquisition and preparation steps (B0
      shimming, water frequency determination, receiver gain optimization, and water
      suppression) combined with short TE , optimized first order projection based B0
      shimming, water suppression, and inner-volume saturated point resolved
      spectroscopy (PRESS) at 3 T is suggested. Simultaneous lipid and trimethylamine
      quantification is demonstrated by means of phantom, volunteer, and representative
      patient measurements. Precise localization of the voxel despite respiratory
      motion, increased spectral quality (higher signal-to-noise ratio and reduced
      linewidth) compared with measurements without respiratory gating, and the
      possibility of acquiring data without additional subject instructions regarding
      breathing enable robust and accurate liver (1)H MRS measurements with this novel
      acquisition protocol.

PMID- 24591126
TI  - A novel osteogenic oxysterol compound for therapeutic development to promote bone
      growth: activation of hedgehog signaling and osteogenesis through smoothened
      binding.
AB  - Osteogenic factors are often used in orthopedics to promote bone growth, improve
      fracture healing, and induce spine fusion. Osteogenic oxysterols are naturally
      occurring molecules that were shown to induce osteogenic differentiation in vitro
      and promote spine fusion in vivo. The purpose of this study was to identify an
      osteogenic oxysterol more suitable for clinical development than those previously
      reported, and evaluate its ability to promote osteogenesis in vitro and spine
      fusion in rats in vivo. Among more than 100 oxysterol analogues synthesized,
      Oxy133 induced significant expression of osteogenic markers Runx2, osterix (OSX),
      alkaline phosphatase (ALP), bone sialoprotein (BSP), and osteocalcin (OCN) in
      C3H10T1/2 mouse embryonic fibroblasts and in M2-10B4 mouse marrow stromal cells.
      Oxy133-induced activation of an 8X-Gli luciferase reporter, its direct binding to
      Smoothened, and the inhibition of Oxy133-induced osteogenic effects by the
      Hedgehog (Hh) pathway inhibitor, cyclopamine, demonstrated the role of Hh pathway
      in mediating osteogenic responses to Oxy133. Oxy133 did not stimulate
      osteogenesis via BMP or Wnt signaling. Oxy133 induced the expression of OSX, BSP,
      and OCN, and stimulated robust mineralization in primary human mesenchymal stem
      cells. In vivo, bilateral spine fusion occurred through endochondral ossification
      and was observed in animals treated with Oxy133 at the fusion site on X-ray after
      4 weeks and confirmed with manual assessment, micro-CT (uCT), and histology after
      8 weeks, with equal efficiency to recombinant human bone morphogenetic protein-2
      (rhBMP-2). Unlike rhBMP-2, Oxy133 did not induce adipogenesis in the fusion mass
      and resulted in denser bone evidenced by greater bone volume/tissue volume
      (BV/TV) ratio and smaller trabecular separation. Findings here suggest that
      Oxy133 has significant potential as an osteogenic molecule with greater ease of
      synthesis and improved time to fusion compared to previously studied oxysterols.
      Small molecule osteogenic oxysterols may serve as the next generation of bone
      anabolic agents for therapeutic development.

PMID- 24591127
TI  - Tissue factor pathway inhibitor-2 silencing promotes hepatocellular carcinoma
      cell invasion in vitro.
AB  - Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death in the
      world and metastasis is an essential aspect of HCC progression. Tissue factor
      pathway inhibitor-2 (TFPI-2) has been implicated as a potential suppressor gene
      to regulate tumor invasion and metastasis. In this study, we silenced TFPI-2 in
      the HCC cell line MHCC97-L and evaluated the role of TFPI-2 in cell invasion and
      its impact on gene expression. We showed in this study that stable TFPI-2
      downregulation in MHCC97-L cells resulted in increased cell adhesion and
      invasion. We also showed that mRNA and protein expression levels of MMP-1/3,
      CD44, and ICAM-1 were increased, while those of MMP-2/9 were not changed by TFPI
      2 silencing. Furthermore, silencing of TFPI-2 caused increased Akt
      phosphorylation level and NF-kappaB transcription in MHCC97-L cells. In
      conclusion, this study confirms that TFPI-2 downregulation can contribute to
      tumor invasion of HCC cells through alteration in the expression of metastasis
      related genes.

PMID- 24591130
TI  - Identifying primate species.

PMID- 24591128
TI  - Regional and epi- to endocardial differences in transmural angles of left
      ventricular cardiomyocytes measured in ex vivo pig hearts: functional
      implications.
AB  - Recent studies point toward the existence of a significant population of
      cardiomyocytes that intrude transmurally, in addition to those aligned
      tangentially. Our aim was to investigate the extent of transmural angulation in
      the porcine left ventricle using diffusion tensor magnetic resonance imaging
      (DTMRI). Hearts from eight 15 kg pigs were arrested in diastole. The ventricles
      were filled with polymer to maintain the end-diastolic dimensions. All hearts
      were examined using DTMRI to assess the distribution of transmural angulation of
      the cardiomyocytes at 12 predetermined locations covering the entirety of the
      left ventricle. We found significant differences between the regions, as well as
      within the transmural subcomponents. In eight out of the 12 predetermined mural
      segments, the highest mean transmural angle was located sub-endocardially. The
      greatest mean transmural angles were found in the anterior basal region,
      specifically 14.9 +/- 6.0-degree angle, with the greatest absolute value being
      34.3-degree angle. This is the first study to show the significant
      heterogeneities in the distribution of helical and transmural angles within the
      entirety of the left ventricular walls, not only for different depths within the
      ventricular walls, but also between different ventricular regions. The results
      show unequivocally that not all the contractile elements are aligned exclusively
      in tangential fashion within the left ventricle. The main function of the
      transmurally intruding component is most likely to equalize and normalize
      shortening of the cardiomyocytes at all depths within the myocardium, but our
      findings also support the notion of antagonistic forces existing within the
      myocardial walls.

PMID- 24591131
TI  - The species in primatology.
AB  - Biologists of the late eighteenth and early nineteenth centuries all bandied
      about the term "species," but very rarely actually said what they meant by it.
      Often, however, one can get inside their thinking by piecing together some of
      their remarks. One of the most nearly explicit-appropriately, for the man who
      wrote a book called The Origin of Species - was Charles Darwin: "Practically,
      when a naturalist can unite two forms together by others having intermediate
      characters, he treats the one as a variety of the other... He later translated
      this into evolutionary terms: "Hereafter, we shall be compelled to acknowledge
      that the only distinction between species and well-marked varieties is, that the
      latter are known, or believed, to be connected at the present day by intermediate
      gradations, whereas species were formerly thus connected"(1:484-5.) 

PMID- 24591132
TI  - Recognizing species, present and past.
AB  - Nobody disputes that nature is meaningfully "packaged" in some way. But debate
      persists over exactly how (and even whether) the boundaries dividing taxa should
      (can) be drawn. At one end of the scale, some zealots abstrusely deny real
      existence to higher taxa.(1) At the other, laborers at the taxonomic rock-face
      confront genuine challenges in recognizing and delineating the species that
      systematists agree constitute the most fundamental unit of taxonomic analysis. 

PMID- 24591133
TI  - Primate taxonomy: species and conservation.
AB  - Primatology as a discrete branch of science involving the study of primate
      behavior and ecology took off in the 1960s after discovery of the importance of
      primates as models for biomedical research and the realization that primates
      provide insights into the evolutionary history of humans. Osman Hill's
      unfortunately incomplete monograph series on the comparative anatomy and taxonomy
      of the primates(1) and the Napiers' 1967 A Handbook of Living Primates(2)
      recorded the world's view of primate diversity at this time. This taxonomy
      remained the baseline for nearly three decades, with the diversity of each genus
      being represented by some species, but extensively as subspecies. 

PMID- 24591134
TI  - Species concepts, diversity, and evolution in primates: lessons to be learned
      from mouse lemurs.
AB  - Humans primarily rely on vision when categorizing the world. If you just look at
      the same-sized but strikingly differently colored Neotropical poison-dart frogs
      such as strawberry frogs (Fig. ), you would be convinced that they must belong to
      different species. However, this is an excellent example of a polymorphic
      species, meaning that although these frogs look quite different, mating decisions
      are made based on their conspicuous and species-specific advertisements calls,
      which are not primarily linked to specific color pattern. The situation is quite
      different among nocturnal primates living in dense forest environments, such as
      the tiny nocturnal Malagasy mouse lemurs. In this case, even geographically
      isolated, well-accepted species look superficially quite similar and are
      therefore often termed cryptic species (Fig. ). Some morphs are a bit larger than
      others or show minor phenotypic differences, but morph-specific differences are
      difficult to detect in living subjects. This phenomenon explains why, until the
      end of the last century, species diversity in mouse lemurs was assumed to be low,
      with only two morphologically distinct species. Over the last two decades,
      several international working groups, including our own, undertook a massive
      island-wide sampling effort, including DNA sequencing and phylogenetic analyses
      of mouse lemurs. These revealed a 10-fold higher species diversity, with 21
      currently described species. Are these new species, mostly defined based on the
      phylogenetic species concept (sensu Cracraft), or independent evolutionary
      lineages or, perhaps, only artifacts of taxonomic inflation? What is a species?
      How can we identify primate species? How and why do species emerge during
      evolution?

PMID- 24591135
TI  - Gene flow happens.
AB  - Debate over what is a species was already considered old hat when Darwin wrote
      his seminal abstract (as he called it) more than 150 years ago.(1) Endless
      papers, workshops, and symposia have been presented in an effort to "solve" the
      species problem. Yet, here we are, at it again. Has there been any progress? I
      believe that there has been, and that among the many advances enabled by the
      genomics revolution, progress on species concepts and species recognition is
      among them. To quote Feder and colleagues,(2) we are on the brink of a "unified
      theory of speciation genomics." 

PMID- 24591136
TI  - Defining species in an advanced technological landscape.
AB  - The answer to the proffered question, "What is a species?" is considered one of
      the fundamental issues of biological science, as well as one of the most
      polarizing and sometimes acrimonious problems. Dozens of species concepts have
      been defined, but none are universal for implementation across all taxa. Within
      the past thirty years, the ability to analyze DNA data has progressed to the
      point that multiple methodologies can be simultaneously applied to the same
      evolutionary questions. The use of restriction fragment length polymorphisms,
      microsatellites, and mitochondrial (mtDNA) and nuclear DNA (nucDNA) sequence data
      has unarguably changed how we look at diversity and intensified the concept
      debate through the proliferation of species descriptions. Over the past two
      decades, Madagascar's biodiversity has gone through a tremendous taxonomic
      expansion by the elevation of subspecies to species and through novel
      descriptions, especially within the nocturnal lemurs. With the tremendous
      continuous loss of habitat, exponential human population growth, and stochastic
      changes predicted over coming decades, elucidating the earth's biodiversity will
      never be more important than now. Here, we examine species concepts and their
      attendant criteria. We predict how technological advances will alter, improve
      and, we hope, fully consolidate the unity of thoughts related to this central
      topic of evolutionary biology and its numerous interconnected disciplines. 

PMID- 24591137
TI  - So what is a species anyway? A primatological perspective.
AB  - Since Darwin's time, the question "what a species" has provoked fierce disputes
      and a tremendous number of publications, from short opinion papers to thick
      volumes. The debates covered fundamental philosophical questions, such as: Do
      species exist at all independently of a human observer or are they just a
      construct of the human mind to categorize nature's organismic diversity and serve
      as a semantic tool in human communication about biodiversity? or: Are species
      natural kinds (classes) or individuals that are "born" by speciation, change in
      course of time, and finally "die" when they go extinct or diverge into new
      species? Also included was the problem of species as taxa (taxonomic) versus
      species as products of the speciation process (evolutionary). More pragmatic
      issues arose, such as: How can we reliably delineate and delimitate species? The
      great interest in what a species is reflects the importance of "species" as
      fundamental units in most fields of biology, especially evolutionary biology,
      ecology, and conservation. 

PMID- 24591138
TI  - A pragmatic approach to the species problem from a paleontological perspective.
AB  - The ideal scenario for paleontologists would be for the species they designate to
      be equivalent to the species recognized for modern animals, in the sense that
      they were formed as a result of the same evolutionary processes. This would mean,
      for example, that we could be confident that in combining extant and extinct taxa
      in phylogenetic analyses we would be dealing with equivalent operational
      taxonomic units. Notwithstanding the many thousands of pages that have been spent
      arguing over species concepts, the only concept that has won widespread
      acceptance for the designation of modern species is Mayr's Biological Species
      Concept (BSC).(1) In fact, whenever we complete a cladistic analysis, we assume
      reproductive isolation of our terminal taxa because otherwise their similarities
      could be the product of interbreeding rather than common ancestry. Fundamentally,
      we all behave as though the BSC is true. 

PMID- 24591139
TI  - Species: beasts of burden.
AB  - Ernst Mayr (1904-2005) was the twentieth century's most influential writer to
      wrestle with the species problem. The following draws heavily on his work, albeit
      without presumptuously claiming to mirror his thinking or present any original
      ideas. As a personal meditation, I am thinking mostly of platyrrhines. Following
      Mayr, I adhere to what is commonly called the Biological Species Concept (BSC) as
      a way of thinking about a species in the real-world biosphere as a taxon. I also
      hold to the idea that the Linnaean category called species has the same function
      as other categories: a linguistic tool for organizing and retrieving information
      about biodiversity while embodying evolutionary hypotheses. In other words, alpha
      taxonomy, the area of systematics that involves identifying, naming, and
      classifying species, is not purely an exercise in either biology or inventory
      because it involves communication as well. The burdensome work of the species
      category stems partly from tension created by the several purposes associated
      with the concept: the objective observation and examination of a fundamental
      biological phenomenon, the collection and interpretation of data in a selective
      context of relevance, and the intention to deploy scientific decisions as a form
      of communication within a dynamic but highly structured language system. 

PMID- 24591140
TI  - Delimitating species in paleoanthropology.
AB  - Evolutionary biologists created a large twentieth-century literature about
      delimiting biological species. Paleontologists contributed the unique
      complications of deep time. Toward century's end, one participant wrote: "In all
      probability more paper has been consumed on the questions of the nature and
      definition of the species than any other subject in evolutionary and systematic
      biology." 

PMID- 24591141
TI  - Species in the primate fossil record.
AB  - Species in the fossil record are population pools of genetic and phenetic
      variation at a place and time, morphologically recognizable and distinguishable
      from others by empirical standards. Change through time can be substantial,
      requiring subdivision of lineages that becomes more arbitrary as they become more
      complete. Evolution is about form, space, and time; it is about variation and
      change. Interpretation of species in the fossil record touches all of these. 

PMID- 24591142
TI  - A Darwinian species definition and its implications.
AB  - A review of the vast literature on the epistemology and ontology of "species" is
      far beyond the capacity of both the writer and the length-allotment of this
      essay, limiting it to a somewhat dogmatic presentation of personal opinions, few
      of them original. Also prohibited by the prescribed word limit is an account of
      species concepts considered but not adopted; in many cases, their omission does
      not do justice to their intellectual content. 

PMID- 24591143
TI  - Identifying primate species: themes and perspectives.

PMID- 24591144
TI  - Are the elderly with oropharyngeal carcinoma undertreated?
AB  - OBJECTIVES/HYPOTHESIS: To determine if elderly patients with oropharyngeal
      squamous cell carcinoma (OPSCC) are receiving less treatment and to evaluate the
      benefit of aggressive therapy in this population. STUDY DESIGN: Retrospective
      analysis of a large population database. METHODS: Patients in the Surveillance,
      Epidemiology, and End Results database with OPSCC diagnosed from 2004 to 2009
      were included. The patients were categorized into age groups 45 to 54, 55 to 64,
      65 to 74, 75 to 84, and 85 years and older, then further categorized by treatment
      status. Kaplan-Meier analysis of disease-specific survival (DSS) for late-stage
      (III and IV) OPSCC was performed for all age and treatment categories, followed
      by a multivariate cox regression of treatment status, tumor site, race, stage,
      and sex per age group. RESULTS: A total of 14,909 patients with OPSCC were
      identified. In our demographic data, we observed a significant increase in the
      number of patients who did not receive treatment (surgery, radiation, or combined
      therapy) after age 55. Kaplan-Meier analysis showed that age groups 65 to 74 and
      75 to 84 had substantial benefits in DSS with surgery, radiation, or combined
      therapy. Multivariable analysis did not demonstrate any statistically significant
      difference in the hazard ratios for combined treatment among age groups 45 to 54,
      55 to 64, 65 to 74, and 75 to 84. CONCLUSIONS: Proportionally fewer elderly
      patients with OPSCC are being treated than younger individuals. These patients
      can have significant benefits from aggressive treatments despite their older age
      as shown by our survival analysis. We recommend the use of objective measures to
      assess patient fitness to reduce the potential for undertreatment in the elderly
      population.

PMID- 24591145
TI  - Variants of the inosine triphosphate pyrophosphatase gene and relapse risk
      following treatment for HCV genotype 2/3.

PMID- 24591146
TI  - Validation of the Intimate Bonds Measure for women who are pregnant or have
      recently given birth in Vietnam.
AB  - INTRODUCTION: Sensitive, valid measures to assess the quality of the intimate
      partner relationship are necessary for both clinical practice and research. The
      aim of this study was to examine the validity of the Intimate Bonds Measure (IBM)
      in women who were pregnant or had recently given birth in Vietnam. METHODS: The
      IBM was translated and culturally verified in a step-by-step process with
      Vietnamese health workers, researchers and community members. The validation
      study was nested within two larger community-based cross-sectional
      investigations: the first in 2006, which recruited 199 pregnant women and 165
      mothers of newborns, and the second in 2010, which recruited 419 pregnant women.
      Internal structure was assessed by factor analysis and Cronbach's alpha and
      construct validity by comparison with relevant factors. RESULTS: Exploratory
      factor analyses revealed an identical factor structure to the one reported by the
      measure's developers in an Anglophone Australian population more than 20 years
      ago. The two factors replicate exactly the Care and Control subscales and
      Cronbach's alpha (from 0.68 to 0.83) indicates high internal consistency in both
      sub-scales. Mean scores of the Care-V and Control-V sub-scales were associated
      significantly and in expected directions with whether a woman could confide in,
      felt supported by or was frightened of her partner, or had experienced intimate
      partner violence and measures of mental health status. DISCUSSION: The Vietnamese
      version of the IBM (IBM-V) is comprehensible, meaningful and appears to be a
      valid measure the construct of quality of relationship with an intimate partner
      among women in this setting.

PMID- 24591147
TI  - Ion channels in the endometrium: regulation of endometrial receptivity and embryo
      implantation.
AB  - BACKGROUND: Although embryo implantation is a prerequisite for human
      reproduction, it remains a poorly understood process. The molecular mechanisms
      regulating endometrial receptivity and/or embryo implantation are still largely
      unclear. METHODS: Pubmed and Medline literature databases were searched for
      articles in English published up to December 2013 with relevant keywords
      including 'endometrium', 'Na(+), Cl(-), K(+), or Ca(2+) channels', 'ion
      channels', 'endometrial receptivity', 'blastocyst implantation' and 'embryo
      implantation'. RESULTS: At the time of writing, more than 14 types of ion
      channels, including the cystic fibrosis transmembrane conductance regulator,
      epithelial sodium channel and various Ca(2+) and K(+) channels, had been reported
      to be expressed in the endometrium or cells of endometrial origin. In vitro
      and/or in vivo studies conducted on different species, including rodents, pigs
      and humans, demonstrated the involvement of various ion channels in the process
      of embryo implantation by regulating: (i) uterine luminal fluid volume; (ii)
      decidualization; and (iii) the expression of the genes associated with
      implantation. Importantly, abnormal ion channel expression was found to be
      associated with implantation failure in IVF patients. CONCLUSIONS: Ion channels
      in the endometrium are emerging as important players in regulating endometrial
      receptivity and embryo implantation. Abnormal expression or function of ion
      channels in the endometrium may lead to impaired endometrial receptivity and/or
      implantation failure. Further investigation into the roles of endometrial ion
      channels may provide a better understanding of the complex process of embryo
      implantation and thus reveal novel targets for diagnosis and treatment of
      implantation failure.

PMID- 24591148
TI  - Self-immolative bioluminogenic quinone luciferins for NAD(P)H assays and reducing
      capacity-based cell viability assays.
AB  - Highly sensitive self-cleavable trimethyl lock quinone-luciferin substrates for
      diaphorase were designed and synthesized to measure NAD(P)H in biological samples
      and monitor viable cells via NAD(P)H-dependent cellular oxidoreductase enzymes
      and their NAD(P)H cofactors. 

PMID- 24591149
TI  - Proteomic and genomic analyses suggest the association of apolipoprotein C1 with
      abdominal aortic aneurysm.
AB  - PURPOSE: Abdominal aortic aneurysm (AAA) is an important cause of mortality in
      the elderly. Mouse models are widely used to investigate AAA pathogenesis but
      their suitability for biomarker discovery is unexplored. EXPERIMENTAL DESIGN: We
      conducted a three-phase study. Phase 1: Aortas from angiotensin-II-infused
      apolipoprotein E deficient (ApoE(-/-) ) mice with and without AAA were assessed
      via iTRAQ and analyzed in silico to identify potential circulating markers.
      Microarray data from ApoE(-/-) mice and human patients were analyzed in parallel.
      Phase 2: Putative markers were compared between datasets to shortlist common
      candidates. Phase 3: The relationship of two shortlisted markers and AAA presence
      was assessed. RESULTS: iTRAQ identified eight proteins with biomarker potential.
      Microarray data identified 72 and 96 potential biomarkers from ApoE(-/-) mice and
      human patients, respectively. All three datasets suggested apolipoprotein C1
      (ApoC1) as a marker for AAA; microarray data identified matrix metalloproteinase
      9 (MMP9) as a second potential marker. Plasma ApoC1 and MMP9 concentrations
      positively correlated with AAA diameter in ApoE(-/-) mice. CONCLUSIONS AND
      CLINICAL RELEVANCE: ApoC1 may be a novel biomarker for AAA.

PMID- 24591150
TI  - ROS signalling between endothelial cells and cardiac cells.
AB  - The heart contains not only cardiomyocytes but also other cell types such as
      endothelial cells and fibroblasts. Functional crosstalk among these cell types is
      important for normal cardiac function and is also involved in disease
      pathophysiology. Recent data indicate that redox signalling within and between
      endothelial cells and cardiomyocytes, both through direct and indirect
      mechanisms, is an important aspect of the functional communication between these
      cell types. Such signalling influences contractile function, cardiomyocyte
      growth, hypertrophy, angiogenesis, and fibrosis, and may play an important role
      in cardiac remodelling in disease. 

PMID- 24591152
TI  - Dickkopf-3: a stubborn protector of cardiac hypertrophy.

PMID- 24591151
TI  - Cell-cell interaction in the heart via Wnt/beta-catenin pathway after cardiac
      injury.
AB  - The adult mammalian heart predominantly comprises myocytes, fibroblasts,
      endothelial cells, smooth muscle cells, and epicardial cells arranged in a
      precise three-dimensional framework. Following cardiac injury, the spatial
      arrangement of cells is disrupted as different populations of cells are recruited
      to the heart in a temporally regulated manner. The alteration of the cellular
      composition of the heart after cardiac injury thus enables different phenotypes
      of cells to interact with each other in a spatio-temporal-dependent manner. It
      can be argued that the integrated study of such cellular interactions rather than
      the examination of single populations of cells can provide more insights into the
      biology of cardiac repair especially at an organ-wide level. Many signalling
      systems undoubtedly mediate such cross talk between cells after cardiac injury.
      The Wnt/beta-catenin system plays an important role during cardiac development
      and disease. Here, we describe how cell populations in the heart after cardiac
      injury mediate their interactions via the Wnt/beta-catenin pathway, determine how
      such interactions can affect a cardiac repair response and finally suggest an
      integrated approach to study cardiac cellular interactions. 

PMID- 24591153
TI  - Halogenated bisphenol-A analogs act as obesogens in zebrafish larvae (Danio
      rerio).
AB  - Obesity has increased dramatically over the past decades, reaching epidemic
      proportions. The reasons are likely multifactorial. One of the suggested causes
      is the accelerated exposure to obesity-inducing chemicals (obesogens). However,
      out of the tens of thousands of industrial chemicals humans are exposed to, very
      few have been tested for their obesogenic potential, mostly due to the limited
      availability of appropriate in vivo screening models. In this study, we
      investigated whether two commonly used flame retardants, the halogenated
      bisphenol-A (BPA) analogs tetrabromobisphenol-A (TBBPA) and tetrachlorobisphenol
      A (TCBPA), could act as obesogens using zebrafish larvae as an in vivo animal
      model. The effect of embryonic exposure to these chemicals on lipid accumulation
      was analyzed by Oil Red-O staining, and correlated to their capacity to activate
      human and zebrafish peroxisome proliferator-activated receptor gamma (PPARgamma)
      in zebrafish and in reporter cell lines. Then, the metabolic fate of TBBPA and
      TCBPA in zebrafish larvae was analyzed by high-performance liquid chromatography
      (HPLC) . TBBPA and TCBPA were readily taken up by the fish embryo and both
      compounds were biotransformed to sulfate-conjugated metabolites. Both halogenated
      BPAs, as well as TBBPA-sulfate induced lipid accumulation in zebrafish larvae.
      TBBPA and TCBPA also induced late-onset weight gain in juvenile zebrafish. These
      effects correlated to their capacity to act as zebrafish PPARgamma agonists.
      Screening of chemicals for inherent obesogenic capacities through the zebrafish
      lipid accumulation model could facilitate prioritizing chemicals for further
      investigations in rodents, and ultimately, help protect humans from exposure to
      environmental obesogens. 

PMID- 24591154
TI  - Tempol protects cardiomyocytes from nucleoside reverse transcriptase inhibitor
      induced mitochondrial toxicity.
AB  - Nucleoside reverse transcriptase inhibitors (NRTIs), essential components of
      combinational therapies used for treatment of human immunodeficiency virus-1,
      damage heart mitochondria. Here, we have shown mitochondrial compromise in H9c2
      rat cardiomyocytes exposed for 16 passages (P) to the NRTIs zidovudine (AZT,
      50MUM) and didanosine (ddI, 50MUM), and we have demonstrated protection from
      mitochondrial compromise in cells treated with 200MUM 1-oxyl-2,2,6,6-tetramethyl
      4-hydroxypiperidine (Tempol) or 200MUM 1-hydroxy-4-[2-triphenylphosphonio)
      acetamido]-2,2,6,6-tetramethylpiperidine (Tempol-H), along with AZT/ddI, for 16P.
      Exposure to AZT/ddI caused a moderate growth inhibition at P3, P5, P7, and P13,
      which was not altered by addition of Tempol or Tempol-H. Mitochondrial oxidative
      phosphorylation capacity was determined as uncoupled oxygen consumption rate
      (OCR) by Seahorse XF24 Analyzer. At P5, P7, and P13, AZT/ddI-exposed cells showed
      an OCR reduction of 8.8-57.2% in AZT/ddI-exposed cells, compared with unexposed
      cells. Addition of Tempol or Tempol-H, along with AZT/ddI, resulted in OCR levels
      increased by about 300% above the values seen with AZT/ddI alone. The Seahorse
      data were further supported by electron microscopy (EM) studies in which P16
      cells exposed to AZT/ddI/Tempol had less mitochondrial pathology than P16 cells
      exposed to AZT/ddI. Western blots of P5 cells showed that Tempol and Tempol-H
      upregulated expression of mitochondrial uncoupling protein-2 (UCP-2). However,
      Complex I activity that was reduced by AZT/ddI, was not restored in the presence
      of AZT/ddI/Tempol. Superoxide levels were increased in the presence of AZT/ddI
      and significantly decreased in cells exposed to AZT/3TC/Tempol at P3, P7, and
      P10. In conclusion, Tempol protects against NRTI-induced mitochondrial
      compromise, and UCP-2 plays a role through mild uncoupling. 

PMID- 24591156
TI  - Synthesis, antioxidant, and antiacetylcholinesterase activities of sulfonamide
      derivatives of dopamine-related compounds.
AB  - A series of sulfonamides were synthesized from dopamine derivatives. The
      reactions of amines with methanesulfonyl chloride followed by O-demethylation
      with BBr3 afforded phenolic sulfonamides. The antioxidant activities of the
      synthesized phenolic sulfonamides were investigated by thiocyanate method, 2,2'
      azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS(*+)), 1,1-diphenyl-2
      picryl-hydrazyl (DPPH(*)), N,N-dimethyl-p-phenylenediamine (DMPD(*+)), and
      superoxide anion (O2(*-)) radical scavenging, reducing power, and ferrous ion
      (Fe(2+)) chelating assays. Sulfonamides 13-16 showed around 75-85% inhibition on
      linoleic acid peroxidation. On the other hand, butylated hydroxyanisole (BHA),
      butylated hydroxytoluene (BHT), alpha-tocopherol, and trolox indicated an
      inhibition of 90.0%, 85.73%, 73.33%, and 85.73% on peroxidation, respectively, in
      the same system at the same concentration (10 ug/mL). Also, the inhibition
      effects of the synthesized compounds on acetylcholinesterase (AChE) activity were
      evaluated. AChE was effectively inhibited by sulfanomides 13-16, with K(i) values
      in the range of 33.04 +/- 4.3 to 131.68 +/- 8.8 nM.

PMID- 24591155
TI  - Catechol-o-methyltransferase and 3,4-({+/-})-methylenedioxymethamphetamine
      toxicity.
AB  - Metabolism of 3,4-(+/-)-methylenedioxymethamphetamine (MDMA) is necessary to
      elicit its neurotoxic effects. Perturbations in phase I and phase II hepatic
      enzymes can alter the neurotoxic profile of systemically administered MDMA. In
      particular, catechol-O-methyltransferase (COMT) plays a critical role in
      determining the fraction of MDMA that is converted to potentially neurotoxic
      metabolites. Thus, cytochrome P450 mediated demethylenation of MDMA, or its N
      demethylated metabolite, 3,4-(+/-)-methylenedioxyamphetamine, give rise to the
      catechols, N-methyl-alpha-methyldopamine and alpha-methyldopamine, respectively.
      Methylation of these catechols by COMT limits their oxidation and conjugation to
      glutathione, a process that ultimately gives rise to neurotoxic metabolites. We
      therefore determined the effects of modulating COMT, a critical enzyme involved
      in determining the fraction of MDMA that is converted to potentially neurotoxic
      metabolites, on MDMA-induced toxicity. Pharmacological inhibition of COMT in the
      rat potentiated MDMA-induced serotonin deficits and exacerbated the acute MDMA
      induced hyperthermic response. Using a genetic mouse model of COMT deficiency, in
      which mice lack a functional COMT gene, such mice displayed greater reductions in
      dopamine concentrations relative to their wild-type (WT) counterparts. Neither WT
      nor COMT deficient mice were susceptible to MDMA-induced decreases in serotonin
      concentrations. Interestingly, mice devoid of COMT were far more susceptible to
      the acute hyperthermic effects of MDMA, exhibiting greater increases in body
      temperature that ultimately resulted in death. Our findings support the view that
      COMT plays a pivotal role in determining the toxic response to MDMA. 

PMID- 24591157
TI  - Design, synthesis, biological evaluation, and molecular modeling of coumarin
      piperazine derivatives as acetylcholinesterase inhibitors.
AB  - Acetylcholinesterase (AChE) is an important drug target for the treatment of
      Alzheimer's disease. A novel series of coumarin-piperazine derivatives were
      synthesized and their potency to inhibit human AChE enzyme (hAChE) was studied.
      All the final compounds were characterized by infrared, (1)H NMR, (13)C NMR, and
      elemental analysis. Docking experiments of the designed coumarin-piperazine
      derivatives were carried out in order to compare the theoretical and experimental
      binding affinities toward hAChE, to delineate the inhibitory mechanism.
      Subsequently, a structure-activity relationship (SAR) study using the molecular
      field method showed that the hydrophobic field and positive charge center
      conferred by the coumarin and piperazine moieties demonstrated an inhibitory
      mechanism. Among the compounds tested, 3f, 3j, and 3m were found to be the most
      potent inhibitors of hAChE.

PMID- 24591160
TI  - Questions on therapy with DPP-4 inhibitors and bone homeostasis.
AB  - A recent study from Gallagher et al. aimed to investigate the effect of a new
      depeptidyl-peptidase-4 inhibitor, MK-0626, on bone turnover in a mouse model
      developing insulin resistance and diabetes (MKR mice). Authors have found that
      treatment with MK-0626 did not affect either MKR mice fasting glucose or
      parameters of bone metabolism. These data are not in accordance with previous
      findings, raising questions on the possible protective effect of depeptidyl
      peptidase-4 inhibitors on bone loss. Given the negative effects on the bone
      caused by some antidiabetic drugs, results from this study may be disappointing,
      but a neutral effect on the bone is still reassuring. However, some aspects of
      this study should be considered in order to explain these results, and more
      studies are needed to better understand the effect of this class of drugs on the
      bone health in humans.

PMID- 24591163
TI  - Hydroxy functionalization of non-activated C-H and C=C bonds: new perspectives
      for the synthesis of alcohols through biocatalytic processes.
AB  - New perspectives through enzymes: Recent breakthroughs have been achieved in the
      selective hydroxy functionalization of non-activated C-H and C=C bonds. Enzymes
      turned out to be suitable catalysts for the omega-hydroxylation of (substituted)
      alkanes and regioselective hydroxylation of aromatic hydrocarbons with
      atmospheric oxygen as the oxidant, and the asymmetric addition of water to non
      activated alkenes.

PMID- 24591164
TI  - A collision of history, controversy, and meditation.

PMID- 24591162
TI  - Understanding interactions of functionalized nanoparticles with proteins: a case
      study on lactate dehydrogenase.
AB  - Nanomaterials in biological solutions are known to interact with proteins and
      have been documented to affect protein function, such as enzyme activity.
      Understanding the interactions of nanoparticles with biological components at the
      molecular level will allow for rational designs of nanomaterials for use in
      medical technologies. Here we present the first detailed molecular mechanics
      model of functionalized gold nanoparticle (NP) interacting with an enzyme (L
      lactate dehydrogenase (LDH) enzyme). Molecular dynamics (MD) simulations of the
      response of LDH to the NP binding demonstrate that although atomic motions
      (dynamics) of the main chain exhibit only a minor response to the binding, the
      dynamics of side chains are significantly constrained in all four active sites
      that predict alteration in kinetic properties of the enzyme. It is also
      demonstrated that the 5 nm gold NPs cause a decrease in the maximal velocity of
      the enzyme reaction (V(max)) and a trend towards a reduced affinity (increased
      K(m)) for the beta-NAD binding site, while pyruvate enzyme kinetics (K(m) and
      V(max)) are not significantly altered in the presence of the gold NPs. These
      results demonstrate that modeling of NP:protein interactions can be used to
      understand alterations in protein function.

PMID- 24591165
TI  - Intercalation-driven reversible control of magnetism in bulk ferromagnets.
AB  - An extension in magnetoelectric effects is proposed to include reversible
      chemistry-controlled magnetization variations. This ion-intercalation-driven
      magnetic control can be fully reversible and pertinent to bulk material volumes.
      The concept is demonstrated for ferromagnetic iron oxide where the intercalated
      lithium ions cause valence change and partial redistribution of Fe(3+) cations
      yielding a large and fully reversible change in magnetization at room
      temperature. 

PMID- 24591166
TI  - Single-step gas-phase polyperfluoroalkylation of naphthalene leads to
      thermodynamic products.
AB  - High-temperature gas-phase, solvent- and catalyst-free reaction of naphthalene
      with an excess of RF I reagent (RF ?CF3 , C2 F5 , n-C3 F7 , and n-C4 F9 ) was
      used for the first time to produce a series of highly perfluoroalkylated
      naphthalene products NAPH(RF )n with n=2-5. Four 95+ % pure 1,3,5,7-NAPH(RF )4
      with RF ?CF3 , C2 F5 , n-C3 F7 , and n-C4 F9 were isolated using a simple
      chromatography-free procedure. These new compounds were fully characterized by
      (19) F and (1) H NMR spectroscopy, X-ray crystallography (for RF ?CF3 and C2 F5
      ), atmospheric-pressure chemical ionization mass spectrometry, and cyclic and
      square-wave voltammetry. DFT calculations confirm that the proposed synthesis
      yields the most stable isomers that have not been accessed by alternative
      preparation techniques. 

PMID- 24591167
TI  - Issue highlights--Cytometry Part B March 2014.

PMID- 24591170
TI  - The FM/AM world is shaping the future of deep brain stimulation.

PMID- 24591168
TI  - Properties of human blood monocytes. I. CD91 expression and log orthogonal light
      scatter provide a robust method to identify monocytes that is more accurate than
      CD14 expression.
AB  - BACKGROUND: This study was designed to improve identification of human blood
      monocytes by using antibodies to molecules that occur consistently on all stages
      of monocyte development and differentiation. METHODS: We examined blood samples
      from 200 healthy adults without clinically diagnosed immunological abnormalities
      by flow cytometry (FCM) with multiple combinations of antibodies and with a
      hematology analyzer (Beckman LH750). RESULTS: CD91 (alpha2 -macroglobulin
      receptor) was expressed only by monocytes and to a consistent level among
      subjects [mean median fluorescence intensity (MFI) = 16.2 +/- 3.2]. Notably, only
      85.7 +/- 5.82% of the CD91(+) monocytes expressed high levels of the classical
      monocyte marker CD14, with some CD91(+) CD16(+) cells having negligible CD14,
      indicating that substantial FCM under-counts will occur when monocytes are
      identified by high CD14. CD33 (receptor for sialyl conjugates) was co-expressed
      with CD91 on monocytes but CD33 expression varied by nearly ten-fold among
      subjects (mean MFI = 17.4 +/- 7.7). In comparison to FCM analyses, the hematology
      analyzer systematically over-counted monocytes and eosinophils while lymphocyte
      and neutrophil differential values generally agreed with FCM methods.
      CONCLUSIONS: CD91 is a better marker to identify monocytes than CD14 or CD33.
      Furthermore, FCM (with anti-CD91) identifies monocytes better than a currently
      used clinical CBC instrument. Use of anti-CD91 together with anti-CD14 and anti
      CD16 supports the identification of the diagnostically significant monocyte
      populations with variable expression of CD14 and CD16.

PMID- 24591171
TI  - Brain SPECT in Sydenham's chorea in remission.
AB  - BACKGROUND: Sydenham's chorea, a major manifestation of rheumatic fever, is
      characterized by chorea, behavioral changes, and cognitive dysfunction. Perfusion
      changes in the basal ganglia are the most frequent imaging findings observed in
      patients with Sydenham's chorea. METHODS: Twelve adult women with Sydenham's
      chorea in remission underwent brain single-photon emission computed tomography
      (SPECT). Their scans underwent a quantification process to evaluate the perfusion
      of Brodmann's areas of the frontal lobes and basal ganglia. The results were
      compared with the findings from a control group that was matched by age. RESULTS:
      A pattern of hyperperfusion in the left putamen was observed in the patient group
      (P = 0.02). No significant difference was observed in relation to other brain
      regions. CONCLUSIONS: The findings of brain SPECT suggest that perfusion
      abnormalities of the basal ganglia may persist even after the remission of
      abnormal movements in patients with Sydenham's chorea.

PMID- 24591172
TI  - Paraneoplastic movement disorders in childhood.

PMID- 24591173
TI  - Capillary electrophoresis for the analysis of paralytic shellfish poisoning
      toxins in shellfish: comparison of detection methods.
AB  - Paralytic shellfish toxins (PSTs) are produced by marine and freshwater
      microalgae and accumulate in shellfish including mussels, oysters, and scallops,
      causing possible fatalities when inadvertently consumed. Monitoring of PST
      content of shellfish is therefore important for food safety, with currently
      approved methods based on HPLC, using pre- or postcolumn oxidation for
      fluorescence detection (HPLC-FLD). CE is an attractive alternative for screening
      and detection of PSTs as it is compatible with miniaturization and could be
      implemented in portable instrumentation for on-site monitoring. In this study, CE
      methods were developed for C(4) D, FLD, UV absorption detection, and MS-making
      this first report of C(4) D and FLD for PSTs detection. Because most oxidized
      toxins are neutral, MEKC was used in combination with FLD. The developed CZE-UV
      and CZE-C(4) D methods provide better resolution, selectivity, and separation
      efficiency compared to CZE-MS and MEKC-FLD. The sensitivity of the CZE-C(4) D and
      MEKC-FLD methods was superior to UV and MS, with LOD values ranging from 140 to
      715 ng/mL for CZE-C(4) D and 60.9 to 104 ng/mL for MEKC-FLD. With the regulatory
      limit for shellfish samples of 800 ng/mL, the CZE-C(4) D and MEKC-FLD methods
      were evaluated for the screening and detection of PSTs in shellfish samples.
      While the CZE-C(4) D method suffered from significant interferences from the
      shellfish matrix, MEKC-FLD was successfully used for PST screening of a periodate
      oxidized mussel sample, with results confirmed by HPLC-FLD. This confirms the
      potential of MEKC-FLD for screening of PSTs in shellfish samples. 

PMID- 24591175
TI  - Plasmid DNA purification using a multimodal chromatography resin.
AB  - Multimodal chromatography is widely used for isolation of proteins because it
      often results in improved selectivity compared to conventional separation resins.
      The binding potential and chromatographic behavior of plasmid DNA have here been
      examined on a Capto Adhere resin. Capto Adhere is a recent multimodal
      chromatography material allowing molecular recognition between the ligand and
      target molecule, which is based on combined ionic and aromatic interactions.
      Capto Adhere proved to offer a very strong binding of nucleic acids. This
      property could be used to isolate plasmid DNA from a crude Escherichia coli
      extract. Using a stepwise NaCl gradient, pure plasmid DNA could be obtained
      without protein and endotoxin contaminations. The RNA fraction bound most
      strongly to the resin and could be eluted only at very high salt concentrations
      (2.0 M NaCl). The chromatographic separation behavior was very robust between pH
      values 6 and 9, and the dynamic binding capacity was estimated to 60 ug/ml resin.

PMID- 24591174
TI  - Interaction investigations of crustacean beta-GBP recognition toward pathogenic
      microbial cell membrane and stimulate upon prophenoloxidase activation.
AB  - In invertebrates, crustaceans' immune system consists of pattern recognition
      receptors (PRRs) instead of immunoglobulin's, which involves in the microbial
      recognition and initiates the protein-ligand interaction between hosts and
      pathogens. In the present study, PRRs namely beta-1,3 glucan binding protein
      (beta-GBP) from mangrove crab Episesarma tetragonum and its interactions with the
      pathogens such as bacterial and fungal outer membrane proteins (OMP) were
      investigated through microbial aggregation and computational interaction studies.
      Molecular recognition and microbial aggregation results of Episesarma tetragonum
      beta-GBP showed the specific binding affinity toward the fungal beta-1,3 glucan
      molecule when compared to other bacterial ligands. Because of this microbial
      recognition, prophenoloxidase activity was enhanced and triggers the innate
      immunity inside the host animal. Our findings disclose the role of beta-GBP in
      molecular recognition, host-pathogen interaction through microbial aggregation,
      and docking analysis. In vitro results were concurred with the in silico docking,
      and molecular dynamics simulation analysis. This study would be helpful to
      understand the molecular mechanism of beta-GBP and update the current knowledge
      on the PRRs of crustaceans.

PMID- 24591176
TI  - Yeast two-hybrid screen reveals novel protein interactions of the cytoplasmic
      tail of lipophorin receptor in silkworm brain.
AB  - The silkworm, Bombyx mori lipophorin receptor (BmLpR), is expressed as splice
      variants. The alternative splicing of its primary gene transcripts yields four
      isoforms namely, LpR1 through 4. Among these isoforms, the LpR4 is unique,
      expressed only in the brain and CNS and with a unique amino acid tail sequence in
      its cytoplasmic domain. We carried out yeast two-hybrid screens to identify
      effector proteins that interact specifically with the cytoplasmic tail of LpR4
      from a cDNA library derived from silkworm brain. The validity of the screen was
      confirmed by immunoblotting and further by co-immunoprecipitation. We have
      identified 11 novel proteins that are capable of interacting with the cytoplasmic
      domain of LpR4 in the silkworm brain. Most of these newly identified target
      proteins have known functions in lipid signalling, protein kinase pathways, cell
      motility, and organization of cytoskeleton, neurotransmission, and
      neuroprotection. These findings, for the first time, demonstrate a molecular link
      between LpR4 and the interacting proteins that might be involved in the
      regulation of signalling pathways in silkworm brain.

PMID- 24591177
TI  - NMR screening of new carbocyanine dyes as ligands for affinity chromatography.
AB  - Four new carbocyanines containing symmetric and asymmetric heterocyclic moieties
      and N-carboxyalkyl groups have been synthesized and characterized. The binding
      mechanism established between these cyanines and several proteins was evaluated
      using saturation transfer difference (STD) NMR. The results obtained for the
      different dyes revealed a specific interaction to the standard proteins lysozyme,
      alpha-chymotrypsin, ribonuclease (RNase), bovine serum albumin (BSA), and gamma
      globulin. For instance, the two un-substituted symmetrical dyes (cyanines 1 and
      3) interacted preferentially through its benzopyrrole and dibenzopyrrole units
      with lysozyme, alpha-chymotrypsin, and RNase, whereas the symmetric
      disulfocyanine dye (cyanine 2) bound BSA and gamma globulin through its
      carboxyalkyl chains. On the other hand, the asymmetric dye (cyanine 4) interacts
      with lysozyme and alpha-chymotrypsin through benzothiazole moiety and with RNase
      through dibenzopyrrole unit. Thus, STD-NMR technique was successfully used to
      screen cyanine-protein interactions and determine potential binding sites of the
      cyanines for posterior use as ligands in affinity chromatography.

PMID- 24591178
TI  - Direct and indirect interactions in the recognition between a cross-neutralizing
      antibody and the four serotypes of dengue virus.
AB  - Dengue fever is the most important vector-borne viral disease. Four serotypes of
      dengue virus, DENV1 to DENV4, coexist. Secondary infection by a different
      serotype is a risk factor for severe dengue. Monoclonal antibody mAb4E11
      neutralizes the four serotypes of DENV with varying efficacies by recognizing an
      epitope located within domain-III (ED3) of the viral envelope (E) protein. To
      better understand the cross-reactivities between mAb4E11 and the four serotypes
      of DENV, we constructed mutations in both Fab4E11 fragment and ED3, and we
      searched for indirect interactions in the crystal structures of the four
      complexes. According to the serotype, 7 to 12 interactions are mediated by one
      water molecule, 1 to 10 by two water molecules, and several of these interactions
      are conserved between serotypes. Most interfacial water molecules make hydrogen
      bonds with both antibody and antigen. Some residues or atomic groups are engaged
      in both direct and water-mediated interactions. The doubly-indirect interactions
      are more numerous in the complex of lowest affinity. The third complementarity
      determining region of the light chain (L-CDR3) of mAb4E11 does not contact ED3.
      The structures and double-mutant thermodynamic cycles showed that the effects of
      (hyper)-mutations in L-CDR3 on affinity were caused by conformational changes and
      indirect interactions with ED3 through other CDRs. Exchanges of residues between
      ED3 serotypes showed that their effects on affinity were context dependent. Thus,
      conformational changes, structural context, and indirect interactions should be
      included when studying cross-reactivity between antibodies and different
      serotypes of viral antigens for a better design of diagnostics, vaccine, and
      therapeutic tools against DENV and other Flaviviruses.

PMID- 24591179
TI  - Compound prioritization from inverse docking experiment using receptor-centric
      and ligand-centric methods: a case study on Plasmodium falciparum Fab enzymes.
AB  - Prioritization of compounds using inverse docking approach is limited owing to
      potential drawbacks in its scoring functions. Classically, molecules ranked by
      best or lowest binding energies and clustering methods have been considered as
      probable hits. Mining probable hits from an inverse docking approach is very
      complicated given the closely related protein targets and the chemically similar
      ligand data set. To overcome this problem, we present here a computational
      approach using receptor-centric and ligand-centric methods to infer the
      reliability of the inverse docking approach and to recognize probable hits. This
      knowledge-driven approach takes advantage of experimentally identified inhibitors
      against a particular protein target of interest to delineate shape and molecular
      field properties and use a multilayer perceptron model to predict the biological
      activity of the test molecules. The approach was validated using flavone
      derivatives possessing inhibitory activities against principal antimalarial
      molecular targets of fatty acid biosynthetic pathway, FabG, FabI and FabZ,
      respectively. We propose that probable hits can be retrieved by comparing the
      rank list of docking, quantitative-structure activity relationship and multilayer
      perceptron models.

PMID- 24591182
TI  - Editorial: Biotechnology Journal in Asia - the first official AFOB special issue.
AB  - The first AFOB special issue of Biotechnology Journal is edited by Prof. Tai Hyun
      Park and Prof. George G. Q. Chen. The eleven articles are representative of the
      diverse nature of biotechnology today, covering topics such as microfluidic
      devices, high-throughput analysis, biosensors, bio-imaging, tissue engineering,
      vaccination, gene delivery, gene expression, and cell-free protein synthesis. 

PMID- 24591180
TI  - Dynamic and geometric analyses of Nudaurelia capensis omega virus maturation
      reveal the energy landscape of particle transitions.
AB  - Quasi-equivalent viruses that infect animals and bacteria require a maturation
      process in which particles transition from initially assembled procapsids to
      infectious virions. Nudaurelia capensis omega virus (NomegaV) is a T = 4,
      eukaryotic, single-stranded ribonucleic acid virus that has proved to be an
      excellent model system for studying the mechanisms of viral maturation.
      Structures of NomegaV procapsids (diameter = 480 A), a maturation intermediate
      (410 A), and the mature virion (410 A) were determined by electron cryo
      microscopy and three-dimensional image reconstruction (cryoEM). The cryoEM
      density for each particle type was analyzed with a recently developed maximum
      likelihood variance (MLV) method for characterizing microstates occupied in the
      ensemble of particles used for the reconstructions. The procapsid and the mature
      capsid had overall low variance (i.e., uniform particle populations) while the
      maturation intermediate (that had not undergone post-assembly autocatalytic
      cleavage) had roughly two to four times the variance of the first two particles.
      Without maturation cleavage, the particles assume a variety of microstates, as
      the frustrated subunits cannot reach a minimum energy configuration. Geometric
      analyses of subunit coordinates provided a quantitative description of the
      particle reorganization during maturation. Superposition of the four quasi
      equivalent subunits in the procapsid had an average root mean square deviation
      (RMSD) of 3 A while the mature particle had an RMSD of 11 A, showing that the
      subunits differentiate from near equivalent environments in the procapsid to
      strikingly non-equivalent environments during maturation. Autocatalytic cleavage
      is clearly required for the reorganized mature particle to reach the minimum
      energy state required for stability and infectivity.

PMID- 24591186
TI  - Imaging and tracing of intracellular metabolites utilizing genetically encoded
      fluorescent biosensors.
AB  - Intracellular metabolites play a crucial role in characterizing and regulating
      corresponding cellular activities. Tracking intracellular metabolites in real
      time by traditional means was difficult until the powerful toolkit of genetically
      encoded biosensors was developed. Over the past few decades, iterative
      improvements of these biosensors have been made, resulting in the effective
      monitoring of metabolites. In this review, we introduce and discuss the recent
      advances in the use of genetically encoded biosensors for tracking some key
      metabolites, such as ATP, cAMP, cGMP, NADH, reactive oxygen species, sugar,
      carbon monoxide, and nitric oxide. A brief phylogeny of fluorescent proteins and
      several typical construction modes for genetically encoded biosensors are also
      described. We also discuss the development of novel RNA-based sensors, which are
      genetically encoded biosensors active at the transcriptional level. 

PMID- 24591190
TI  - Obstructive sleep apnea in patients undergoing endoscopic surgical repair of
      cerebrospinal fluid rhinorrhea.
AB  - OBJECTIVES/HYPOTHESIS: To examine the relationship between cerebrospinal fluid
      (CSF) rhinorrhea and obstructive sleep apnea (OSA). STUDY DESIGN: Retrospective
      chart review of patients who underwent surgical repair of encephaloceles and/or
      CSF rhinorrhea at a tertiary medical center over a 12-year period. METHODS:
      Pertinent demographic, clinical, and surgical data including age, sex, and
      medical and surgical history were obtained. Patients were classified by etiology
      of CSF leak into a spontaneous leak group and a nonspontaneous leak group, which
      included patients with documented trauma, malignancy, or known iatrogenic injury.
      RESULTS: We retrospectively identified 126 patients who underwent repair of
      encephalocele or CSF rhinorrhea. Of these, 70 (55.5%) were found to have a
      spontaneous etiology, whereas 56 (44.4%) had a nonspontaneous cause. Patients
      with spontaneous CSF rhinorrhea were more likely than their nonspontaneous
      counterparts to have a diagnosis of OSA (30.0% vs. 14.3%, P = .0294) and
      radiographic evidence of an empty sella on magnetic resonance imaging MRI (55.4%
      vs. 24.3%, P = .0027). Overall, patients in the spontaneous CSF rhinorrhea group
      were more likely to be female compared to the nonspontaneous group (84.3% vs.
      41.1% female, P = .0001). CONCLUSIONS: Our study shows that patients with
      spontaneous CSF rhinorrhea are significantly more likely to have a diagnosis of
      OSA compared to those with nonspontaneous causes of CSF leaks, or to the general
      population (incidence of 1%-5% in various population studies). Given the known
      association between OSA and intracranial hypertension (ICH), it may be prudent to
      screen all patients with spontaneous CSF rhinorrhea for symptoms of OSA as well
      as for ICH, and vice versa. LEVEL OF EVIDENCE: 4

PMID- 24591191
TI  - Effects of sublingual immunotherapy for Dermatophagoides farinae on Th17 cells
      and CD4(+) CD25(+) regulatory T cells in peripheral blood of children with
      allergic asthma.
AB  - BACKGROUND: Sublingual immunotherapy is becoming a more common treatment for
      allergic diseases, particularly in pediatric clinics. This type of treatment is
      highly effective for Dermatophagoides farinae allergy, but the mechanisms
      resulting in immune tolerance have not been investigated. We explored the effects
      of sublingual immunotherapy with D. farinae drops on populations of subsets of T
      immune cells, specifically Th17 cells and CD4(+) CD25(+) regulatory T cells (Treg
      cells), in peripheral blood of children with allergic asthma. METHODS: We
      assessed immune cell populations in 60 patients allergic to D. farinae who were
      randomly divided into 2 groups: a treatment group (n = 30) and a control group (n
      = 30), treated with sublingual administration of D. farinae drops or placebo,
      respectively, for 48 weeks. Clinical symptoms of asthma were scored for each
      individual before and after treatment, and the percentages of Th17 cells and
      CD4(+) CD25(+) Treg cells in the peripheral blood were evaluated by flow
      cytometry at 12-week intervals beginning at baseline. RESULTS: Both the mean
      daily symptom scores and percentages of Th17 cells significantly declined in the
      treatment group throughout the study period (p < 0.05), and in the control group
      both declined but without significant differences between time points. In
      contrast, the percentages of Treg cells significantly increased in the treatment
      group throughout the study period (p < 0.05), but no statistical difference was
      observed among different sampling times. CONCLUSION: Sublingual administration of
      D. farinae drops alters T immune cell profiles and reduces asthma symptoms,
      likely resulting in enhanced immunosuppression in children with asthma.

PMID- 24591192
TI  - Historical, present, and future significance of corticosteroid in the treatment
      of acute liver failure.

PMID- 24591194
TI  - Mapping of SPECT regional cerebral perfusion abnormalities in obsessive
      compulsive disorder.
AB  - Locations of cerebral perfusion abnormalities in obsessive-compulsive disorder
      (OCD) were mapped with single photon emission computed tomography (SPECT) and
      magnetic resonance imaging (MRI). This report is a new, more thorough analysis of
      a previous study of these subjects that used region-of-interest methods. Ten
      obsessive-compulsive patients and seven age- and sex-matched control subjects
      were studied. Image sets were converted into stereotaxic space, normalized to
      each subject's mean cerebral value, then group averaged. Difference images were
      calculated and searched for regions with significant between-group cerebral
      perfusion differences. Obsessive-compulsive patients had significantly higher
      relative cerebral perfusion in medial-frontal and right frontal cortex and in
      cerebellum, and significantly reduced perfusion in right visual association
      cortex. Increased frontal Perfusion agrees with several prior reports. The
      caudate nucleus, which has been controversial in neuroimaging studies of OCD, did
      not display a difference between groups. The results of this study provide
      information about the locations and extents of cerebral perfusion abnormalities
      in OCD. Regional abnormalities were compared with those reported in prior
      functional neuroimaging studies. Issues related to OCD hyperfrontality and
      frontal lateralization of psychopathology are discussed. Normal caudate nucleus
      findings are considered in relation to prior functional imaging studies and
      hypotheses of OCD pathology. (c) 1994 Wiley-Liss, Inc. 

PMID- 24591195
TI  - Human brain metabolic responses to familiarity during lexical decision.
AB  - Local cerebral glucose metabolic rate was measured using F18-DG/PET in 11 normal
      righthanded male volunteers performing two versions of a visual lexical decision
      task differing only with respect to whether the stimuli were all novel and shown
      only once, or whether they were all repeated many times. Each subject was also
      scanned in a resting state (eyes open and ears unplugged). Scalp recordings of
      cognitive evoked potentials in the same subjects and tasks confirmed that the
      effects of familiarity were present during the entire 30 min FDG uptake period.
      The N4 (a left temporoparietal negativity 400 ms after stimulus onset) decreased
      with repetition, and the P3b (a 600 ms latency parietal positivity) increased.
      The pattern of metabolic activation was also significantly different between the
      three experimental conditions. Planned comparisons of the tasks with the resting
      condition revealed significant relative activations of visual and motor areas.
      Novel words evoked significantly greater activation in the left and right
      anterior cingulate gyri and right hippocampal formation than did repeated words
      in the same task. Relative glucose metabolism in the left angular gyrus was
      significantly greater to novel words than to resting. Thus, two tasks equated in
      sensory, motor, and decision processes, but differing in the familiarity of the
      stimuli, evoke significantly different patterns of brain activation. The patterns
      observed provided evidence that recent episodic memory for words engages a system
      that includes the bilateral anterior cingulate gyri, the medial temporal lobe,
      and the left angular gyrus. (c) 1994 Wiley-Liss, Inc. 

PMID- 24591196
TI  - Neural modeling and functional neuroimaging.
AB  - Two research areas that so far have had little interaction with one another are
      functional neuroimaging and computational neuroscience. The application of
      computational models and techniques to the inherently rich data sets generated by
      "standard" neurophysiological methods has proven useful for interpreting these
      data sets and for providing predictions and hypotheses for further experiments.
      We suggest that both theory- and data-driven computational modeling of neuronal
      systems can help to interpret data generated by functional neuroimaging methods,
      especially those used with human subjects. In this article, we point out four
      sets of questions, addressable by computational neuroscientists whose answere
      would be of value and interest to those who perform functional neuroimaging. The
      first set consist of determining the neurobiological substrate of the signals
      measured by functional neuroimaging. The second set concerns developing systems
      level models of functional neuroimaging data. The third set of questions involves
      integrating functional neuroimaging data across modalities, with a particular
      emphasis on relating electromagnetic with hemodynamic data. The last set asks how
      one can relate systems-level models to those at the neuronal and neural ensemble
      levels. We feel that there are ample reasons to link functional neuroimaging and
      neural modeling, and that combining the results from the two disciplines will
      result in furthering our understanding of the central nervous system. (c) 1994
      Wiley-Liss, Inc. This Article is a US Goverment work and, as such, is in the
      public domain in the United State of America. 

PMID- 24591193
TI  - Grassypeptolides as natural inhibitors of dipeptidyl peptidase 8 and T-cell
      activation.
AB  - Natural products made by marine cyanobacteria are often highly modified peptides
      and depsipeptides that have the potential to act as inhibitors for proteases. In
      the interests of finding new protease inhibition activity and selectivity,
      grassypeptolide A (1) was screened against a panel of proteases and found to
      inhibit DPP8 selectively over DPP4. Grassypeptolides were also found to inhibit
      IL-2 production and proliferation in activated T-cells, consistent with a
      putative role of DPP8 in the immune system. These effects were also observed in
      Jurkat cells, and DPP activity in Jurkat cell cytosol was shown to be inhibited
      by grassypeptolides. In silico docking suggests two possible binding modes of
      grassypeptolides-at the active site of DPP8 and at one of the entrances to the
      internal cavity. Collectively these results suggest that grassypeptolides might
      be useful tool compounds in the study of DPP8 function. 

PMID- 24591197
TI  - Functional neuroanatomy of verbal free recall: A replication study.
AB  - The functional neuroanatomy of verbal memory was investigated using verbal free
      recall during H2 (15) O positron emission tomography (PET). Twelve young (25-40
      years old) normal control subjects participated in eight scans during a single
      scanning session during which they performed three memory tasks differing by word
      list length. Four subjects also had scans during a "rest" condition. Temporal
      lobe activation was observed during all tasks, including single-word repetition.
      The frontal cortices, specifically Brodmann areas 9 and 10, were activated only
      when the recall word lists exceeded the memory spans (i. e., 12 and 15 words).
      Activation was also observed in the anterior cingulate cortex (BA24 and BA32).
      These data, obtained using a within-subject design, extend previously reported
      findings that used mixed within-and between-subject designs and demonstrate
      important functional components of normal auditoryverbal short-term memory. (c)
      1994 Wiley-Liss, Inc. 

PMID- 24591198
TI  - Activation of the prefrontal cortex in a nonspatial working memory task with
      functional MRI.
AB  - Functional magnetic resonance imaging (fMRI) was used to examine the pattern of
      activity of the prefrontal cortex during performance of subjects in a nonspatial
      working memory task. Subjects observed sequences of letters and responded
      whenever a letter repeated with exactly one nonidentical letter intervening. In a
      comparison task, subjects monitored similar sequences of letters for any
      occurrence of a single, prespecified target letter. Functional scanning was
      performed using a newly developed spiral scan image acquisition technique that
      provides high-resolution, multislice scanning at approximately five times the
      rate usually possible on conventional equipment (an average of one image per
      second). Using these methods, activation of the middle and inferior frontal gyri
      was reliably observed within individual subjects during performance of the
      working memory task relative to the comparison task. Effect sizes (2-4%) closely
      approximated those that have been observed within primary sensory and motor
      cortices using similar fMRI techniques. Furthermore, activation increased and
      decreased with a time course that was highly consistent with the task
      manipulations. These findings corroborate the results of positron emission
      tomography studies, which suggest that the prefrontal cortex is engaged by tasks
      that rely on working memory. Furthermore, they demonstrate the applicability of
      newly developed fMRI techniques using conventional scanners to study the
      associative cortex in individual subjects. (c) 1994 Wiley-Liss, Inc. 

PMID- 24591199
TI  - Humain brain mapping in both time and Space.

PMID- 24591200
TI  - Soluble human TLR2 ectodomain binds diacylglycerol from microbial lipopeptides
      and glycolipids.
AB  - TLRs are key innate immune receptors that recognize conserved features of
      biological molecules that are found in microbes. In particular, TLR2 has been
      reported to be activated by different kinds of microbial ligands. To advance our
      understanding of the interaction of TLR2 with its ligands, the recombinant human
      TLR2 ectodomain (hTLR2ED) was expressed using a baculovirus/insect cell
      expression system and its biochemical, as well as ligand binding, properties were
      investigated. The hTLR2ED binds synthetic bacterial and mycoplasmal lipopeptides,
      lipoteichoic acid from Staphylococcus aureus, and synthetic lipoarabinomannan
      precursors from Mycobacterium at extracellular physiological conditions, in the
      absence of its co-receptors TLR1 and TLR6. We also determined that lipopeptides
      and glycolipids cannot bind simultaneously to hTLR2ED and that the phosphatidyl
      inositol mannoside 2 (Pim2) is the minimal lipoarabinomannan structure for
      binding to hTLR2ED. Binding of hTLR2ED to Pim4, which contains a diacylglycerol
      group with one of its acyl chains containing 19 carbon atoms, indicates that
      hTLR2ED can bind ligands with acyl chains longer than 16 carbon atoms. In
      summary, our data indicate that diacylglycerol is the ligand moiety of microbial
      glycolipids and lipoproteins that bind to hTLR2ED and that both types of ligands
      bind to the same binding site of hTLR2ED. 

PMID- 24591201
TI  - Randomized trial of bendamustine-rituximab or R-CHOP/R-CVP in first-line
      treatment of indolent NHL or MCL: the BRIGHT study.
AB  - This randomized, noninferiority (NI), global, phase 3 study evaluated the
      efficacy and safety of bendamustine plus rituximab (BR) vs a standard rituximab
      chemotherapy regimen (rituximab plus cyclophosphamide, doxorubicin, vincristine,
      and prednisone [R-CHOP] or rituximab plus cyclophosphamide, vincristine, and
      prednisone [R-CVP]) for treatment-naive patients with indolent non-Hodgkin's
      lymphoma or mantle cell lymphoma. Investigators preassigned the standard
      treatment regimen they considered most appropriate for each patient; patients
      were randomized to receive BR (n = 224) or standard therapy (R-CHOP/R-CVP, n =
      223) for 6 cycles; 2 additional cycles were permitted at investigator discretion.
      Response was assessed by a blinded independent review committee. BR was
      noninferior to R-CHOP/R-CVP, as assessed by the primary end point of complete
      response rate (31% vs 25%, respectively; P = .0225 for NI [0.88 margin]). The
      overall response rates for BR and R-CHOP/R-CVP were 97% and 91%, respectively (P
      = .0102). Incidences of vomiting and drug-hypersensitivity reactions were
      significantly higher in patients treated with BR (P < .05), and incidences of
      peripheral neuropathy/paresthesia and alopecia were significantly higher in
      patients treated with standard-therapy regimens (P < .05). These data indicate BR
      is noninferior to standard therapy with regard to clinical response with an
      acceptable safety profile. This trial was registered at www.clinicaltrials.gov as
      #NCT00877006. 

PMID- 24591202
TI  - Functions of flt3 in zebrafish hematopoiesis and its relevance to human acute
      myeloid leukemia.
AB  - FMS-like tyrosine kinase 3 (FLT3) is expressed in human hematopoietic stem and
      progenitor cells (HSPCs) but its role during embryogenesis is unclear. In acute
      myeloid leukemia (AML), internal tandem duplication (ITD) of FLT3 at the
      juxtamembrane (JMD) and tyrosine kinase (TKD) domains (FLT3-ITD(+)) occurs in 30%
      of patients and is associated with inferior clinical prognosis. TKD mutations
      (FLT3-TKD(+)) occur in 5% of cases. We made use of zebrafish to examine the role
      of flt3 in developmental hematopoiesis and model human FLT3-ITD(+) and FLT3
      TKD(+) AML. Zebrafish flt3 JMD and TKD were remarkably similar to their mammalian
      orthologs. Morpholino knockdown significantly reduced the expression of l-plastin
      (pan-leukocyte), csf1r, and mpeg1 (macrophage) as well as that of c-myb
      (definitive HSPCs), lck, and rag1 (T-lymphocyte). Expressing human FLT3-ITD in
      zebrafish embryos resulted in expansion and clustering of myeloid cells (pu.1(+),
      mpo(+), and cebpalpha(+)) which were ameliorated by AC220 and associated with
      stat5, erk1/2, and akt phosphorylation. Human FLT3-TKD (D835Y) induced
      significant, albeit modest, myeloid expansion resistant to AC220. This study
      provides novel insight into the role of flt3 during hematopoiesis and establishes
      a zebrafish model of FLT3-ITD(+) and FLT3-TKD(+) AML that may facilitate high
      throughput screening of novel and personalized agents. 

PMID- 24591203
TI  - Donor hematopoiesis in mice following total lymphoid irradiation requires host T
      regulatory cells for durable engraftment.
AB  - Total lymphoid irradiation (TLI) with antithymocyte globulin (ATG) is a unique
      regimen that prepares recipients for allogeneic hematopoietic cell
      transplantation by targeting lymph nodes, while sparing large areas of the bone
      marrow. TLI is reported to increase the frequency of CD4(+)CD25(+)FoxP3(+) T
      regulatory cells (Treg) relative to conventional T cells. In this study, barriers
      to hematopoietic stem cell (HSC) engraftment following this nonmyeloablative
      conditioning were evaluated. TLI/ATG resulted in profound lymphoablation but
      endogenous host HSC remained. Initial donor HSC engraftment occurred only in
      radiation exposed marrow sites, but gradually distributed to bone marrow outside
      the radiation field. Sustained donor engraftment required host lymphoid cells
      insofar as lymphocyte deficient Rag2gammac(-/-) recipients had unstable
      engraftment compared with wild-type. TLI/ATG treated wild-type recipients had
      increased proportions of Treg that were associated with increased HSC frequency
      and proliferation. In contrast, Rag2gammac(-/-) recipients who lacked Treg did
      not. Adoptive transfer of Treg into Rag2gammac(-/-) recipients resulted in
      increased cell cycling of endogenous HSC. Thus, we hypothesize that Treg
      influence donor engraftment post-TLI/ATG by increasing HSC cell cycling, thereby
      promoting the exit of host HSC from the marrow niche. Our study highlights the
      unique dynamics of donor hematopoiesis following TLI/ATG, and the effect of Treg
      on HSC activity. 

PMID- 24591204
TI  - Pretransplant administration of imatinib for allo-HSCT in patients with BCR-ABL
      positive acute lymphoblastic leukemia.
AB  - We aimed to evaluate the impact of pretransplant imatinib administration on the
      outcome of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in
      adults with Philadelphia chromosome-positive (Ph(+)) acute lymphoblastic leukemia
      (ALL). We retrospectively analyzed 738 patients with Ph(+) ALL that underwent
      allo-HSCT between 1990 and 2010 using data from the Transplant Registry Unified
      Management Program of the Japan Society of Hematopoietic Cell Transplantation. We
      compared the allo-HSCT outcomes between 542 patients who received imatinib before
      allo-HSCT during the initial complete remission period (imatinib cohort) and 196
      patients who did not receive imatinib (non-imatinib cohort). The 5-year overall
      survival after allo-HSCT was significantly higher in the imatinib cohort than in
      the non-imatinib cohort (59% vs 38%; 95% confidence interval [CI], 31-45%; P <
      .001). Multivariate analysis indicated that pretransplant imatinib administration
      had beneficial effects on overall survival (hazard ratio [HR], 0.57; 95% CI, 0.42
      0.77; P < .001), relapse (HR, 0.66; 95% CI, 0.43-0.99; P = .048), and nonrelapse
      mortality (HR, 0.55; 95% CI, 0.37-0.83; P = .005). In conclusion, our study
      showed that imatinib administration before allo-HSCT had advantageous effects on
      the clinical outcomes of allo-HSCT in patients with Ph(+) ALL.

PMID- 24591206
TI  - Tuning mechanism-based inactivators of neuraminidases: mechanistic and structural
      insights.
AB  - 3-Fluorosialosyl fluorides are inhibitors of sialidases that function by the
      formation of a long-lived covalent active-site adduct and have potential as
      therapeutics if made specific for the pathogen sialidase. Surprisingly, human
      Neu2 and the Trypanosoma cruzi trans-sialidase are inactivated more rapidly by
      the reagent with an equatorial fluorine at C3 than by its axial epimer, with
      reactivation following the same pattern. To explore a possible stereoelectronic
      basis for this, rate constants for spontaneous hydrolysis of the full series of
      four 3-fluorosialosyl fluorides were measured, and ground-state energies for each
      computed. The alpha (equatorial) anomeric fluorides hydrolyze more rapidly than
      their beta anomers, consistent with their higher ground-state energies. However
      ground-state energies do not explain the relative spontaneous reactivities of the
      3-fluoro-epimers. The three-dimensional structures of the two 3-fluoro-sialosyl
      enzyme intermediates of human Neu2 were solved, revealing key stabilizing
      interactions between Arg21 and the equatorial, but not the axial, fluorine.
      Because of changes in geometry these interactions will increase at the transition
      state, likely explaining the difference in reaction rates. 

PMID- 24591205
TI  - High-resolution mapping of epitopes on the C2 domain of factor VIII by analysis
      of point mutants using surface plasmon resonance.
AB  - Neutralizing anti-factor VIII (FVIII) antibodies that develop in patients with
      hemophilia A and in murine hemophilia A models, clinically termed "inhibitors,"
      bind to several distinct surfaces on the FVIII-C2 domain. To map these epitopes
      at high resolution, 60 recombinant FVIII-C2 proteins were generated, each having
      a single surface-exposed residue mutated to alanine or a conservative
      substitution. The binding kinetics of these muteins to 11 monoclonal, inhibitory
      anti-FVIII-C2 antibodies were evaluated by surface plasmon resonance and the
      results compared with those obtained for wild-type FVIII-C2. Clusters of residues
      with significantly altered binding kinetics identified "functional" B-cell
      epitopes, defined as those residues contributing appreciable antigen-antibody
      avidity. These antibodies were previously shown to neutralize FVIII activity by
      interfering with proteolytic activation of FVIII by thrombin or factor Xa, or
      with its binding to phospholipid surfaces, von Willebrand factor, or other
      components of the intrinsic tenase complex. Fine mapping of epitopes by surface
      plasmon resonance also indicated surfaces through which FVIII interacts with
      proteins and phospholipids as it participates in coagulation. Mutations that
      significantly altered the dissociation times/half-lives identified functionally
      important interactions within antigen-antibody interfaces and suggested specific
      sequence modifications to generate novel, less antigenic FVIII proteins with
      possible therapeutic potential for treatment of inhibitor patients.

PMID- 24591207
TI  - A comparative study between conventional and liquid-based cytology in screening
      for anal intraepithelial lesions in HIV-positive patients.
AB  - Anal intraepithelial neoplasia (AIN) is associated with HPV infection and can be
      detected by cytological screening. While conventional exfoliative cytology (CC)
      is a low-cost and nonaggressive method, liquid-based cytology (LBC) tends to give
      clearer readings. Although studies of the efficacy of anal cancer screening
      methods would be of great importance for groups at high risk for AIN, few such
      studies have been conducted. The aim of the present study was to assess the
      concordance of CC and LBC in diagnosing anal pre-neoplastic lesions, and to
      compare cytological results with anoscopy, histopathological, and molecular
      biology findings. Comparative study involving 33 HIV-positive patients, who
      underwent anoscopy and biopsy of suspected lesions. Concordance between the two
      cytology methods was calculated, as were the associations between cytology
      results and findings from other screening methods. A total of 54.5% of cases were
      considered AIN-negative by CC and LBC, and concordance between the two methods
      was statistically significant (P < 0.05). Anoscopy was negative in 15 of the 18
      CC- and LBC-negative cases. CC identified 75% of patients with positive biopsy,
      while LBC identified 85.71% of these patients. Molecular biology results showed
      that patients with LSIL tested positive for the highest number of HPV subtypes.
      The associations between positive biopsy and high grade HPV, HPV 16, and multiple
      HPV infections were not statistically significant. Conventional and liquid-based
      cytology are equally effective in screening for anal preneoplastic lesions.

PMID- 24591211
TI  - Formal total synthesis of kendomycin by way of alkyne metathesis/gold catalysis.
AB  - In an attempt to study the ability of the latest generation of alkyne metathesis
      catalysts to process sterically hindered substrates, two different routes to the
      bacterial metabolite kendomycin (1) were explored. Whereas the cyclization of the
      overcrowded arylalkyne 39 and related substrates turned out to be impractical or
      even impossible, ring closure of the slightly relaxed diyne 45 was achieved in
      excellent yield under notably mild conditions with the aid of the molybdenum
      alkylidyne 2 endowed with triphenylsilanolate ligands. The resulting cycloalkyne
      46 was engaged into a gold-catalyzed hydroalkoxylation, which led to benzofuran
      47 that had already previously served as a late-stage intermediate en route to 1.

PMID- 24591208
TI  - Aminopeptidase activities as prospective urinary biomarkers for bladder cancer.
AB  - PURPOSE: Proteases have been implicated in cancer progression and invasiveness.
      We have investigated the activities, as opposed to simple protein levels, of
      selected aminopeptidases in urine specimens to serve as potential novel
      biomarkers for urothelial cancer. EXPERIMENTAL DESIGN: The unique urinary
      proteomes of males and females were profiled to establish the presence of a
      gender-independent set of aminopeptidases. Samples were also collected from
      patients with urothelial cancer and matched controls. A SOP for urine processing
      was developed taking into account hydration variation. Five specific
      aminopeptidase activity assays, using fluorophoric substrates, were optimized for
      evaluation of marker potential. RESULTS: Nineteen exopeptidases and 21 other
      proteases were identified in urine and the top-five most abundant
      aminopeptidases, identical in both genders, selected for functional studies.
      Depending on the enzyme, activities were consistently lower (p <= 0.05), higher
      or unchanged in the cancer samples as compared to controls. Two selected
      aminopeptidase activities used as a binary classifier resulted in a ROC curve
      with an AUC = 0.898. CONCLUSION AND CLINICAL RELEVANCE: We have developed
      functional assays that characterize aminopeptidase activities in urine specimens
      with adequate technical and intraindividual reproducibility. With further
      testing, it could yield a reliable biomarker test for bladder cancer detection or
      prognostication.

PMID- 24591214
TI  - Charge-assisted halogen bonding: donor-acceptor complexes with variable ionicity.
AB  - Charge-assisted halogen bonding is unambiguously revealed from structural and
      electronic investigations of a series of isostructural charge-transfer complexes
      derived from iodinated tetrathiafulvalene and tetracyanoquinodimethane
      derivatives, (EDT-TTFI2)2(TCNQF(n)), n=0-2, which exhibit variable degrees of
      ionicity. The iodinated tetrathiafulvalene derivative, EDT-TTFI2, associates with
      tetracyanoquinodimethane (TCNQ) and its derivatives of increasing reduction
      potential (TCNQF, TCNQF2) through highly directional C-I???N=C halogen-bond
      interactions. With the less oxidizing TCNQ acceptor, a neutral and insulating
      charge-transfer complex is isolated whereas with the more oxidizing TCNQF2
      acceptor, an ionic, highly conducting charge-transfer salt is found, both of 2:1
      stoichiometry and isostructural with the intermediate TCNQF complex, in which a
      neutral-ionic conversion takes place upon cooling. A correlation between the
      degree of charge transfer and the C-I???N=C halogen-bond strength is established
      from the comparison of the structures of the three isostructural complexes at
      temperatures from 300 to 20 K, thus demonstrating the importance of
      electrostatics in the halogen-bonding interaction. The neutral-ionic conversion
      in (EDT-TTFI2)2(TCNQF) is further investigated through the temperature dependence
      of its magnetic susceptibility and the stretching modes of the C=N groups.

PMID- 24591215
TI  - Electrospun hierarchical CaCo2O4 nanofibers with excellent lithium storage
      properties.
AB  - Hierarchical CaCo2O4 nanofibers (denoted as CCO-NFs) with a unique hierarchical
      structure have been prepared by a facile electrospinning method and subsequent
      calcination in air. The as-prepared CCO-NFs are composed of well-defined
      ultrathin nanoplates that arrange themselves in an oriented manner to form one
      dimensional (1D) hierarchical structures. The controllable formation process and
      possible formation mechanism are also discussed. Moreover, as a demonstration of
      the functional properties of such hierarchical architecture, the 1D hierarchical
      CCO-NFs were investigated as materials for lithium-ion batteries (LIBs) anode;
      they not only delivers a high reversible capacity of 650 mAh g(-1) at a current
      of 100 mA g(-1) and with 99.6% capacity retention over 60 cycles, but they also
      show excellent rate capability with respect to counterpart nanoplates-in
      nanofibers and nanoplates. The high specific surface areas as well as the unique
      feature of hierarchical structures are probably responsible for the enhanced
      electrochemical performance. Considering their facile preparation and good
      lithium storage properties, 1D hierarchical CCO-NFs will hold promise in
      practical LIBs.

PMID- 24591216
TI  - Synthesis of catechol-, pinacol-, and neopentylglycolborane through the
      heterogeneous catalytic B-B hydrogenolysis of diboranes(4).
AB  - A new synthetic approach to hydroboranes catechol-, pinacol-, and
      neopentylglycolborane has been developed. Starting from diboranes(4) B2cat2,
      B2pin2, or B2neop2, the respective boranes were obtained by heterogeneously
      catalyzed cleavage of the B-B bond in the respective diboranes with hydrogen.
      Group 10 metals were found to be effective catalysts for this reaction.

PMID- 24591217
TI  - Regiospecific anomerisation of acylated glycosyl azides and benzoylated
      disaccharides by using TiCl4.
AB  - Chelation induced anomerisation is promoted when Lewis acids, such as TiCl4 or
      SnCl4, coordinate to the pyranose ring oxygen atom and another site, giving rise
      to endocyclic cleavage and isomerisation to the more stable anomer. In this
      research regiospecific site-directed anomerisation is demonstrated. TiCl4 (2.5
      equiv) was employed to induce anomerisation of 15 glycosyl azide and disaccharide
      substrates of low reactivity, and high yields (>75%) and stereoselectivies
      (alpha/beta>9:1) were achieved. The examples included glucopyranuronate,
      galactopyranuronate and mannopyranuronate as well as N-acetylated
      glucopyranuronate and galactopyranuronate derivatives. A disaccharide with the
      alpha1->4 linkage found in polygalacturonan was included. The use of benzoylated
      saccharides was found to be important in disaccharide anomerisation as attempts
      to isomerise related acetyl protected and 2,3-carbonate protected derivatives
      were not successful.

PMID- 24591218
TI  - Optimization of quantum dot-sensitized photoelectrode for realization of visible
      light hydrogen generation.

PMID- 24591219
TI  - Malonyl CoA: A promising target for the treatment of cardiac disease.
AB  - Alterations in cardiac energy metabolism are an important contributor to the high
      incidence and severity of heart disease in the world. These alterations can
      include an impairment of the production of ATP necessary to meet the high energy
      demands of the heart, as well as adverse switches in energy substrate preference
      by the heart. With regard to this latter point, evidence suggests that a decrease
      in cardiac efficiency, caused by a rise in cardiac fatty acid oxidation and/or an
      increase in the uncoupling of glycolysis from glucose oxidation, impairs cardiac
      function and is a contributing factor to cardiac disease. In support of this
      concept, therapeutic strategies that modulate these metabolic pathways and
      increase cardiac efficiency produce beneficial results in the setting of heart
      disease. One such strategy is to increase cardiac malonyl CoA levels, an
      important inhibitor of mitochondrial fatty acid uptake. This includes malonyl CoA
      decarboxylase (MCD) inhibition that results in increased cardiac malonyl CoA
      levels, decreased cardiac fatty acid oxidation rates, and improved cardiac
      efficiency. Preclinical studies have shown that MCD inhibition can improve
      cardiac function in various forms of heart disease. Here, we focus on the
      importance of malonyl CoA in the regulation of cardiac energy metabolism and
      function in the normal and diseased heart and discuss the evidence that suggests
      that inhibition of fatty acid oxidation especially via regulation of malonyl CoA,
      through MCD inhibition, is a promising strategy to treat cardiac disease. (c)
      2014 IUBMB Life, 66(3):139-146, 2014.

PMID- 24591220
TI  - Coagulation-induced resistance to fluid flow in small-diameter vascular grafts
      and graft mimics measured by purging pressure.
AB  - In this study, the coagulation-induced resistance to flow in small-diameter
      nonpermeable Tygon tubes and permeable expanded polytetrafluoroethylene (ePTFE)
      vascular grafts was characterized by measuring the upstream pressure needed to
      purge the coagulum from the tube lumen. This purging pressure was monitored using
      a closed system that compressed the contents of the tubes at a constant rate. The
      pressure system was validated using a glycerin series with well-defined
      viscosities and precisely controlled reductions in cross-sectional area available
      for flow. This system was then used to systematically probe the upstream pressure
      buildup as fibrin glue, platelet-rich plasma (PRP) or whole blood coagulated in
      small-diameter Tygon tubing and or ePTFE grafts. The maximum purging pressures
      rose with increased clot maturity for fibrin glue, PRP, and whole blood in both
      Tygon and ePTFE tubes. Although the rapidly coagulating fibrin glue in
      nonpermeable Tygon tubing yielded highly consistent purging curves, the
      significantly longer and more variable clotting times of PRP and whole blood, and
      the porosity of ePTFE grafts, significantly diminished the consistency of the
      purging curves.

PMID- 24591221
TI  - Retrieval study at 623 human mesh explants made of polypropylene--impact of mesh
      class and indication for mesh removal on tissue reaction.
AB  - Textile meshes frequently are implanted in the abdominal wall to reinforce a
      hernia repair. However, revisions for mesh associated complications confirm that
      these devices are not completely free of risk. Explanted devices offer an
      opportunity to define the impact of mesh structure on tissue response. This
      retrieval study analyses the tissue reaction to 623 polypropylene mesh samples
      (170 class 1 with large pores, and 453 class 2 with small pores) explanted for
      pain, infection, or recurrence. Histopathological assessment included morphometry
      of inflammatory infiltrate (IF) and connective tissue (CT), and of collagen 1/3
      ratio. Half of the meshes were removed after more than 23 month. Despite large
      inter-individual differences removal for infection showed more IF than for pain
      or recurrence with significant correlation of IF with CT. Class 1 meshes with
      large pores showed less IF, CT, fistula formation, calcification, and bridging
      than class 2 meshes with small pores. Meshes removed for recurrence showed a
      lowered collagen 1/3 ratio in 70%. Large pore class 1 meshes showed an improved
      tissue response and may be considered as favorable to prevent inflammatory side
      effects. The presence of lowered collagen 1/3 ratio in most of the samples with
      recurrences stresses the relevance of an intact healing process. Late
      manifestation of complications demands long-lasting follow-up.

PMID- 24591222
TI  - Design and validation of a thermoreversible material for percutaneous tissue
      hydrodissection.
AB  - Interventional oncology procedures such as thermal ablation are becoming routine
      for many cancers. Hydrodissection-separating tissues with fluids-protects tissues
      near the treatment zone to improve ablation's safety and facilitate more
      aggressive treatments. However, currently used fluids such as normal saline and
      5% dextrose in water (D5W) migrate in the peritoneum, reducing their protective
      efficacy. As a hydrodissection alternative, we investigated a thermoreversible
      poloxamer 407 (P407) solution. Such a material can be injected as a liquid which
      then forms a semi-solid gel at body temperature without syneresis. The desired
      gelation temperature of 32 degrees C was achieved with 15.4 wt/wt % P407.
      Viscosity analysis revealed the lowest viscosity and ideal injection point was at
      14 degrees C. Solution viscosity increased during gelation, to a peak of 65 kPa*s
      at 40 degrees C. The electrical impedance of P407 was significantly greater than
      isotonic saline, but lower than D5W, indicating its potential for electrical
      protection. The P407 gel was similar to other hydrodissection fluids at
      ultrasound and CT imaging. Ex vivo liver ablations showed that P407 protects
      neighboring tissues, but may require a thicker barrier for comparable protection
      to D5W. Overall, we found that the P407 solution is a feasible alternative to
      traditional hydrodissection fluids and warrants additional study.

PMID- 24591223
TI  - The effect of ethylene oxide sterilization on the surface chemistry and in vitro
      cytotoxicity of several kinds of chitosan.
AB  - The surfaces of three chitosan samples, differing only in their degrees of
      deacetylation and of carboxyethyl chitosan were chemically characterized by X-ray
      photoelectron spectroscopy, time-of-flight secondary ion mass spectroscopy, X-ray
      diffraction, and Fourier transform infrared, both before and after sterilization
      with ethylene oxide. Unexpected elemental ratios suggest that surface chemical
      modification occurred during the processing of the original chitin, with further
      surface modification on subsequent sterilization, despite previous reports to the
      contrary. Cell viability was evaluated by direct contact methyl thiazole
      tetrazolium and lactate dehydrogenase assays between the chitosan particles and
      A549 human epithelial cells, which demonstrated that the modifications incurred
      on sterilization are reflected in biocompatibility changes. All the samples were
      found to be biocompatible and nontoxic before sterilization and remained so
      subsequently.

PMID- 24591224
TI  - Laser fabrication of porous silicon-based platforms for cell culturing.
AB  - In this study, we explore the selective culturing of human mesenchymal stem cells
      (hMSCs) on Si-based diffractive platforms. We demonstrate a single-step and
      flexible method for producing platforms on nanostructured porous silicon (nanoPS)
      based on the use of single pulses of an excimer laser to expose phase masks. The
      resulting patterns are typically 1D patterns formed by fringes or 2D patterns
      formed by circles. They are formed by alternate regions of almost unmodified
      nanoPS and regions where the nanoPS surface has melted and transformed into Si
      nanoparticles. The patterns are produced in relatively large areas (a few square
      millimeters) and can have a wide range of periodicities and aspect ratios. Direct
      binding, that is, with no previous functionalization of the pattern, alignment,
      and active polarization of hMSCs are explored. The results show the preferential
      direct binding of the hMSCs along the transformed regions whenever their width
      compares with the dimensions of the cells and they escape from patterns for
      smaller widths suggesting that the selectivity can be tailored through the
      pattern period.

PMID- 24591225
TI  - In vitro characteristics of a gelling PEGDA-QT polymer system with model drug
      release for cerebral aneurysm embolization.
AB  - A liquid-to-solid gelling polymer system, such as the poly(ethylene glycol)
      diacrylate-pentaerythritol tetrakis (3-mercaptopropionate) (PEGDA-QT) system, can
      fill cerebral aneurysms more completely than current embolization materials,
      reducing the likelihood of aneurysm recurrence. PEGDA-QT gels were formulated
      using PEGDA of different molecular weights (PEGDA575 and PEGDA700), and their
      characteristics were examined in vitro. Experiments examined gel time, mass
      change, crosslink integrity, cytotoxicity, and protein release capabilities. In
      general, PEGDA575-QT gels were more hydrophobic, requiring an initiating solution
      with a higher pH (pH 9.5) to achieve a gel time comparable to PEGDA700-QT gels,
      which used an initiating solution at pH 9.19. The mass change and crosslink
      integrity of gels were analyzed over time after gels were submerged in 150 mM
      phosphate buffered saline. After 380 days, PEGDA575-QT gels achieved a maximum
      mass increase of 72% due to water uptake, while PEGDA700-QT gels doubled their
      initial mass (100% increase) by 165 days. Compression tests showed that PEGDA700
      QT gels hydrolyzed more quickly than PEGDA575-QT gels. Cytotoxicity assays showed
      that in general, PEGDA575-QT negatively affected cell growth, while PEGDA700-QT
      gels promoted cell viability. Sustained, controlled release of lysozyme, a 14.3
      kDa protein, was achieved over an 8-week period when loaded into PEGDA700-QT
      gels, but PEGDA575-QT gels did not show sustained release. These studies show
      that although they are similar in composition, these PEGDA-QT gel formulations
      behave considerably differently. Although PEGDA700-QT gels swell more and degrade
      faster than PEGDA575-QT gels, their cytocompatibility and protein release
      characteristics may prove to be more beneficial for in vivo aneurysm treatment.

PMID- 24591226
TI  - Biocompatibility and preclinical feasibility tests of a temperature-sensitive
      hydrogel for the purpose of surgical wound pain control and cartilage repair.
AB  - We recently introduced a novel pluronic F127 and hyaluronic acid-based hydrogel
      (HG) designed to deliver a broad range of therapeutics. The reverse-thermal
      responsive HG exhibits physical properties that seem to be ideal for the local
      delivery of drug- and cell-based therapies to specific anatomic sites through
      percutaneous injection. However, questions related to the HG's safety and
      efficacy must first be addressed. To address these issues, we performed standard
      in vitro cytotoxicity and drug release tests and in vivo biocompatibility tests
      in a rat model. In addition, we determined whether the HG was an effective stem
      cell carrier in a rat cartilage defect model. We found that the HG showed
      viability and biocompatibility levels similar to those reported for F127 or
      hyaluronic acid alone. In vitro drug release studies with bupivacaine, a drug
      used clinically for local pain relief, revealed that after an initial burst
      bupivacaine was released continuously for 10 days. Stem cells loaded in the HG
      were retained in situ and stimulated cartilage regeneration in experimental
      defects. Taken as a whole, these findings support further efforts to develop the
      HG as a versatile system for the delivery of a wide range of therapeutic agents
      in humans.

PMID- 24591227
TI  - Manganese-enhanced MRI of minimally gadolinium-enhancing breast tumors.
AB  - PURPOSE: To investigate the potential of manganese (Mn)-enhanced MRI for
      sensitive detection and delineation of tumors that demonstrate little enhancement
      on Gd-DTPA. MATERIALS AND METHODS: Eighteen nude rats bearing 1 to 2 cm in
      diameter orthotopic breast tumors (ZR75 and LM2) were imaged on a 3 Tesla (T)
      clinical scanner. Gd-DTPA was administered intravenously and MnCl2
      subcutaneously, both at 0.05 mmol/kg. T1 -weighted imaging and T1 measurements
      were performed precontrast, 10 min post-Gd-DTPA, and 24 h post-MnCl2 . Tumors
      were excised and histologically assessed using H&E (composition and necrosis) and
      CD34 (vascularity). RESULTS: Most tumors (78%) demonstrated little enhancement (<
      20% change in R1 ) on Gd-DTPA. MnCl2 administration achieved greater and more
      uniform enhancement throughout the tumor mass (i.e., not restricted to the tumor
      periphery), with R1 changing over 20% in 72% of tumors. MnCl2 -induced R1 changes
      compared with Gd-induced changes were significantly greater in both ZR75 (P <
      0.01) and LM2 tumors (P < 0.05). Histology confirmed very low vascularity in both
      tumor models, and necrotic areas were well delineated only on Mn-enhanced MRI.
      CONCLUSION: Mn-enhanced MRI is a promising approach for detection of low-Gd
      enhancing tumors.

PMID- 24591228
TI  - Dystonia after severe brain injuries.

PMID- 24591229
TI  - Differential mechanisms of action of the novel gamma-aminobutyric acid receptor
      antagonist ectoparasiticides fluralaner (A1443) and fipronil.
AB  - BACKGROUND: Fluralaner (A1443) is an isoxazoline ectoparasiticide that is a novel
      antagonist of gamma-aminobutyric acid (GABA) receptors (GABARs), with a potency
      comparable to that of fipronil, a phenylpyrazole ectoparasiticide. To clarify the
      biological effectiveness of fluralaner against fipronil-resistant pests,
      differences in the actions of fluralaner and fipronil on GABARs that possess
      resistance to dieldrin (rdl)-type mutations were evaluated. RESULTS: Fipronil had
      neither pest control nor GABAR-antagonistic activities against two-spotted spider
      mites (Tetranychus urticae) that had two different rdl-type amino acids (A(301) 
      > H and T(350) -> A: Drosophila melanogaster GABAR numbering) and against small
      brown planthoppers (Laodelphax striatellus) that had a novel rdl-type (A(283) ->
      N) mutation in GABARs. In contrast, fluralaner showed not only high pest control
      activities against these pests, but also excellent antagonistic activities for
      these rdl-type GABARs. CONCLUSION: The findings indicate that rdl-type fipronil
      resistant pests do not show cross-resistance to fluralaner owing to the
      differential actions of fluralaner and fipronil on the GABAR.

PMID- 24591230
TI  - Re: Non-invasive prenatal testing for fetal chromosomal abnormalities by low
      coverage whole-genome sequencing of maternal plasma DNA: review of 1982
      consecutive cases in a single center. T. K. Lau, S. W. Cheung, P. S. S. Lo, A. N.
      Pursley, M. K. Chan, F. Jiang, H. Zhang, W. Wang, L. F. J. Jong, O. K. C. Yuen,
      H. Y. C. Chan, W. S. K. Chan and K. W. Choy. Ultrasound Obstet Gynecol 2014; 43:
      254-264.

PMID- 24591231
TI  - Re: Crown-rump length discordance in the first trimester: a predictor of adverse
      outcome in twin pregnancies? M. L. Johansen, A. Oldenburg, S. Rosthoj, J. C.
      Maxild, L. Rode and A. Tabor. Ultrasound Obstet Gynecol 2014; 43: 277-283.

PMID- 24591232
TI  - Reply: To PMID 23939754.

PMID- 24591233
TI  - Re: fetal right ventricular contraction and relaxation times at 11-13 weeks'
      gestation by speckle tracking imaging.

PMID- 24591234
TI  - Chromosomal microarray as first-tier approach in low-risk pregnancies: detection
      rate should not be the only criterion for its application.

PMID- 24591235
TI  - Reply: To PMID 23512800.

PMID- 24591236
TI  - Does plant colour matter? Wax accumulation as an indicator of decline in
      Juniperus thurifera.
AB  - The photosynthesis in evergreen trees living in Mediterranean ecosystems is
      subjected to multiple climatic stresses due to water shortage and high
      temperatures during the summer and to low temperatures during the winter.
      Mediterranean perennials deploy different photoprotective mechanisms to prevent
      damage to the photosynthetic system. Wax accumulation in leaves is a primary
      response which by enhancing light scattering in the leaf surface reduces incident
      radiation in the mesophyll. The existence of high variability in wax accumulation
      levels between coexisting individuals of a species has a visual effect on colour
      that provides distinguishable green and glaucous phenotypes. We explored this
      variability in a Mediterranean evergreen tree Juniperus thurifera (L.) to
      evaluate the impact of epicuticular wax on optical and ecophysiological
      properties and on the abundance of photoprotective pigments throughout an annual
      cycle. Because of light attenuation by waxes, we expected that glaucous
      phenotypes would lower the need for photoprotective pigments. We evaluated the
      effect of phenotype and season on reflectance, defoliation levels, photochemical
      efficiency and photoprotective pigment contents in 20 green and 20 glaucous
      junipers. Contrary to our expectations, the results showed that glaucous trees
      suffered from a diminution in photochemical efficiency, but there was no
      reduction in photoprotective pigments. Differences between glaucous and green
      phenotypes were greater in winter, which is the most stressful season for this
      species. Glaucous individuals also showed the highest levels of leaf defoliation.
      The lower photochemical efficiency of glaucous trees, together with higher
      defoliation rates and equal or greater number of physiological photoprotective
      mechanisms, suggests that in spite of wax accumulation, glaucous trees suffer
      from more severe stress than green ones. This result suggests that changes in
      colouration in Mediterranean evergreens may be a decline indicator. 

PMID- 24591238
TI  - Editorial: Biotechnology Journal's diverse coverage of biotechnology.
AB  - This issue of Biotechnology Journal is a regular issue edited by Prof. Michael
      Wink. The issue covers all the major focus areas of the journal, including
      medical biotechnology, synthetic biology, and novel biotechnological methods. 

PMID- 24591237
TI  - RNA-directed amino acid coupling as a model reaction for primitive coded
      translation.
AB  - The stereochemical theory claims that primitive coded translation initially
      occurred in the RNA world by RNA-directed amino acid coupling. In this study, we
      show that the HIV Tat aptamer RNA is capable of recognizing two consecutive
      arginine residues within the Tat peptide, thus demonstrating how RNA might be
      able to position two amino acids for sequence-specific coupling. We also show
      that this RNA can act as a template to accelerate the coupling of a single
      arginine residue to the N-terminal arginine residue of a peptide primer. The
      results might have implications for our understanding of the origin of
      translation. 

PMID- 24591243
TI  - Model organism proteomics as a tool for the study of host-microbiome
      interactions.
AB  - All organisms live in constant contact with the microbial world. In recent years
      it has become evident that these microbial communities are not only responsible
      for the development of certain diseases, but are also an indispensable factor for
      homeostasis. The inherent complexity of meta-organisms hampers a straightforward
      elucidation of the molecular processes regulating the interactions of the host
      and its microbiome, as well as the influence of exogenic factors, for example,
      nutrition. Modern approaches such as meta-proteomics are now capable of
      deciphering the major processes in microbial communities, but the complete
      analysis of their interactions with their host is still in its infancy. In order
      to get easier access, the study of nonmammalian model organisms bears great
      potential. These organisms provide advantages such as reduced complexity, ease of
      cultivation in great numbers, and amenity to a range of genetic and biochemical
      manipulations. We highlight the potentials provided by model organism proteomics
      for the study of host-microbiome interactions and outline major challenges and
      demands for technological improvements that will be necessary for the
      understanding of the manifold interactions within meta-organisms. 

PMID- 24591244
TI  - Harnessing the evolvability of tricyclic microviridins to dissect protease
      inhibitor interactions.
AB  - Understanding and controlling proteolysis is an important goal in therapeutic
      chemistry. Among the natural products specifically inhibiting proteases
      microviridins are particularly noteworthy. Microviridins are ribosomally produced
      and posttranslationally modified peptides that are processed into a unique,
      cagelike architecture. Here, we report a combined rational and random mutagenesis
      approach that provides fundamental insights into selectivity-conferring moieties
      of microviridins. The potent variant microviridin J was co-crystallized with
      trypsin, and for the first time the three-dimensional structure of microviridins
      was determined and the mode of inhibition revealed. 

PMID- 24591247
TI  - The role of 2,6-diaminopyridine ligands in the isolation of an unprecedented, low
      valent tin complex.
AB  - Stabilization of the central atom in an oxidation state of zero through
      coordination of neutral ligands is a common bonding motif in transition-metal
      chemistry. However, the stabilization of main-group elements in an oxidation
      state of zero by neutral ligands is rare. Herein, we report that the
      transamination reaction of the DAMPY ligand system (DAMPY=2,6-[ArNH-CH2 ]2 (NC5
      H3 ) (Ar=C6 H3 -2,6-iPr2 )) with Sn[N(SiMe3 )2 ]2 produces the DIMPYSn complex
      (DIMPY=(2,6-[ArN?CH]2 (NC5 H3 )) with the Sn atom in a formal oxidation state of
      zero. This is the first example of a tin compound stabilized in a formal
      oxidation state of zero by only one donor molecule. Furthermore, three related
      low-valent Sn(II) complexes, including a [DIMPYSn(II) Cl](+) [SnCl3 ](-) ion
      pair, a bisstannylene DAMPY{Sn(II) [N(SiMe3 )2 ]2 }2 , and the enamine complex
      MeDIMPYSn(II) , were isolated. Experimental results and the conclusions drawn are
      also supported by theoretical studies at the density functional level of theory
      and (119) Sn Mossbauer spectroscopy. 

PMID- 24591248
TI  - 1,2,4-Triazol-3-ylidenes with an N-2,4-dinitrophenyl substituent as strongly pi
      accepting N-heterocyclic carbenes.
AB  - The synthesis and characterisation of a series of new Rh and Au complexes bearing
      1,2,4-triazol-3-ylidenes with a N-2,4-dinitrophenyl (N-DNP) substituent are
      described. IR, NMR, single-crystal X-ray diffraction and computational analyses
      of the Rh complexes revealed that the N-heterocyclic carbenes (NHCs) behaved as
      strong pi acceptors and weak sigma donors. In particular, a natural bond orbital
      (NBO) analysis revealed that the contributions of the Rh->Ccarbene pi backbonding
      interaction energies (DeltaEbb ) to the bond dissociation energies (BDE) of the
      Rh?Ccarbene bond for [RhCl(NHC)(cod)] (cod=1,5-cyclooctadiene) reached up to 63
      %. The Au complex exhibited superior catalytic activity in the intermolecular
      hydroalkoxylation of cyclohexene with 2-methoxyethanol. The NBO analysis
      suggested that the high catalytic activity of the Au(I) complex resulted from the
      enhanced pi acidity of the Au atom. 

PMID- 24591249
TI  - Iron dicarbonyl complexes featuring bipyridine-based PNN pincer ligands with
      short interpyridine C-C bond lengths: innocent or non-innocent ligand?
AB  - A series of iron dicarbonyl complexes with bipyridine-based PNN pincer ligands
      were synthesized and characterized by multinuclear NMR spectroscopy ((1) H, (13)
      C, (15) N, (31) P), IR spectroscopy, cyclic voltammetry, (57) Fe Mossbauer
      spectroscopy, XPS spectroscopy, and single-crystal X-ray diffraction. The
      complexes with the general formula [(R-PNN)Fe(CO)2 ] (5: R-PNN=tBu-PNN=6-[(di
      tert-butylphosphino)methyl]-2,2'-bipyridine, 6: R-PNN=iPr-PNN=6
      [(diisopropylphosphino)methyl]-2,2'-bipyridine, and 7: R-PNN=Ph-PNN=6
      [(diphenylphosphino)methyl]-2,2'-bipyridine) feature differently P-substituted
      PNN pincer ligands. Complexes 5 and 6 were obtained by reduction of the
      corresponding dihalide complexes [(R-PNN)Fe(X)2 ] (1: R=tBu, X=Cl; 2: R=tBu,
      X=Br; 3: R=iPr, X=Cl; 4: R=iPr, X=Br) in the presence of CO. The analogous Ph
      substituted complex 7 was synthesized by a reaction of the free ligand with iron
      pentacarbonyl. The low-spin complexes 5-7 (S=0) are diamagnetic and have
      distorted trigonal bipyramidal structures in solution, whereas in the solid state
      the geometries around the iron are best described as distorted square pyramidal.
      Compared to other structurally characterized complexes with these PNN ligands,
      shortened interpyridine C?C bonds of about 1.43 A were measured. A comparison
      with known examples, theoretically described as metal complexes bearing
      bipyridine pi-radical anions (bpy(.) (-) ), suggests that the complexes can be
      described as Fe(I) complexes with one electron antiferromagnetically coupled to
      the ligand-based radical anions. However, computational studies, at the
      NEVPT2/CASSCF level of theory, reveal that the shortening of the C?C bond is a
      result of extensive pi-backbonding of the iron center into the antibonding
      orbital of the bpy unit. Hence, the description of the complexes as Fe(0)
      complexes with neutral bipyridine units is the favorable one. 

PMID- 24591250
TI  - Graphene versus ohmic metal as source-drain electrode for MoS2 nanosheet
      transistor channel.

PMID- 24591251
TI  - Vocal behavior of black-fronted titi monkeys (Callicebus nigrifrons): acoustic
      properties and behavioral contexts of loud calls.
AB  - Loud calls can be heard over long distances due to their high amplitude and low
      frequency. These calls are commonly used for both within- and between-group
      communication in many bird and primate species. In the Neotropics, mated pairs of
      socially monogamous titi monkeys (genus Callicebus) emit conspicuous, coordinated
      loud calls. These vocalizations appear to play a role in territorial defense, a
      hypothesis derived from studies of only three of the 31 recognized Callicebus
      species. Here, we describe the acoustic properties and organization of the loud
      calls of black-fronted titi monkeys (Callicebus nigrifrons). We compare the
      behavioral and ecological contexts associated with these vocalizations to
      investigate their role in within- and between-group communication, resource
      defense, and mate defense. Black-fronted titi monkeys create loud calls by
      combining a finite number of syllables to form more complex phrases, which are
      assembled to compose long sequences of loud calls. Bioacoustic features
      distinguish the loud calls used in different contexts, involving communication
      within- and between-groups. We found support for the hypothesis that
      vocalizations used for between-group communication are cooperative displays used
      by the mated pair and other group members to regulate access to important food
      resources, such as fruits. On the other hand, we only found weak support for the
      mate defense hypothesis.

PMID- 24591252
TI  - Automatic model-based semantic registration of multimodal MRI knee data.
AB  - PURPOSE: To propose a robust and automated model-based semantic registration for
      the multimodal alignment of the knee bone and cartilage from three-dimensional
      (3D) MR image data. MATERIALS AND METHODS: The movement of the knee joint can be
      semantically interpreted as a combination of movements of each bone. A semantic
      registration of the knee joint was implemented by separately reconstructing the
      rigid movements of the three bones. The proposed method was validated by
      registering 3D morphological MR datasets of 25 subjects into the corresponding T2
      map datasets, and was compared with rigid and elastic methods using two criteria:
      the spatial overlap of the manually segmented cartilage and the distance between
      the same landmarks in the reference and target datasets. RESULTS: The mean Dice
      Similarity Coefficient (DSC) of the overlapped cartilage segmentation was
      increased to 0.68 +/- 0.1 (mean +/- SD) and the landmark distance was reduced to
      1.3 +/- 0.3 mm after the proposed registration method. Both metrics were
      statistically superior to using rigid (DSC: 0.59 +/- 0.12; landmark distance: 2.1
      +/- 0.4 mm) and elastic (DSC: 0.64 +/- 0.11; landmark distance: 1.5 +/- 0.5 mm)
      registrations. CONCLUSION: The proposed method is an efficient and robust
      approach for the automated registration between morphological knee datasets and
      T2 MRI relaxation maps.

PMID- 24591255
TI  - Desacetyluvaricin induces S phase arrest in SW480 colorectal cancer cells through
      superoxide overproduction.
AB  - Annonaceous acetogenins (ACGs) are a group of fatty acid-derivatives with potent
      anticancer effects. In the present study, we found desacetyluvaricin (Dau)
      exhibited notable in vitro antiproliferative effect on SW480 human colorectal
      carcinoma cells with IC50 value of 14 nM. The studies on the underlying
      mechanisms revealed that Dau inhibited the cancer cell growth through induction
      of S phase cell cycle arrest from 11.3% (control) to 33.2% (160 nM Dau), which
      was evidenced by the decreased protein expression of cyclin A Overproduction of
      superoxide, intracellular DNA damage, and inhibition of MEK/ERK signaling
      pathway, were also found involved in cells exposed to Dau. Moreover, pre
      treatment of the cells with ascorbic acid significantly prevented the Dau-induced
      overproduction of superoxide, DNA damage and cell cycle arrest. Taken together,
      our results suggest that Dau induces S phase arrest in cancer cells by firstly
      superoxide overproduction and subsequently the involvement of various signaling
      pathways.

PMID- 24591256
TI  - Pbx1 activates Fgf10 in the mesenchyme of developing lungs.
AB  - Insufficiency of surfactants is a core factor in respiratory distress syndrome,
      which causes apnea and neonatal death, particularly in preterm infants.
      Surfactant proteins are secreted by alveolar type II cells in the lung
      epithelium, the differentiation of which is regulated by Fgf10 elaborated by the
      adjacent mesenchyme. However, the molecular regulation of mesenchymal Fgf10
      during lung development has not been fully understood. Here, we show that Pbx1, a
      homeodomain transcription factor, is required in the lung mesenchyme for the
      expression of Fgf10. Mouse embryos lacking Pbx1 in the lung mesenchyme show
      compact terminal saccules and perinatal lethality with failure of postnatal
      alveolar expansion. Mutant embryos had severely reduced expression of Fgf10 and
      surfactant genes (Spa, Spb, Spc, and Spd) that are essential for alveolar
      expansion for gas exchange at birth. Molecularly, Pbx1 directly binds to the
      Fgf10 promoter and cooperates with Meis and Hox proteins to transcriptionally
      activate Fgf10. Our results thus show how Pbx1 controls Fgf10 in the developing
      lung.

PMID- 24591257
TI  - Intermediate filament: structure, function, and applications in cytology.
AB  - Intermediate filament (IF) constitutes an important cytoskeletal component in
      nearly all the vertebrate cells. IFs are present both in the cytoplasm and in the
      nucleus. They play an important role in providing mechanical strength of the cell
      and tissue, growth and regeneration, cell survival and apoptosis, and finally
      cell migration. IFs are also expressed differentially in different body tissues.
      Therefore, judicious use of IF may provide the diagnosis and confirmation of
      different malignancies. This is particularly helpful in the diagnosis of
      metastatic malignant tumor from an unknown primary. Expression of IFs
      particularly cytokeratin and vimentin is also related to prognosis of tumors. In
      this review, we have discussed the basic structure, dynamics, distribution of IF
      in cells, and its role in diagnosis of cytology. Possible prognostic roles of IF
      are also discussed.

PMID- 24591263
TI  - Atypical Activations of Fronto-Cerebellar Regions During Forethought in Parents
      of Children With ADHD.
AB  - OBJECTIVE: Although several studies suggest heritability of ADHD, only a few
      investigations of possible associations between people at risk and neural
      abnormalities in ADHD exist. In this study, we tested whether parents of children
      with ADHD would show atypical patterns of cerebral activations during
      forethought, a feature of working memory. METHOD: Using Functional Magnetic
      Resonance Imaging (fMRI), we compared 12 parents of children with ADHD and 9
      parents of control children during a forethought task. RESULTS: Parents of
      children with ADHD exhibited significantly increased neural activations in the
      posterior lobes of the cerebellum and in the left inferior frontal gyrus,
      relative to parents of control children. CONCLUSION: These findings are
      consistent with previous reports in children and suggest the fronto-cerebellar
      circuit's abnormalities during forethought in parents of children with ADHD.
      Future studies of people at risk of ADHD are needed to fully understand the
      extent of the fronto-cerebellar heritability.

PMID- 24591264
TI  - Targeting metabotropic glutamate receptors as a new strategy against levodopa
      induced dyskinesia in Parkinson's disease?
AB  - Levodopa-induced dyskinesias (LIDs) represent one major motor disability of
      Parkinson's disease (PD) therapy. Thus, research effort is still devoted to
      finding agents that may improve parkinsonism and concomitantly reduce or avoid
      dyskinesia. Rodent and nonhuman primate models provide useful tools to study the
      molecular and neuronal bases of LIDs. Among the various strategies investigated
      recently, the use of drugs targeting metabotropic glutamate receptors has
      received large attention. In particular, use of antagonists of the subtype 5 of
      metabotropic glutamate receptors revealed promising preclinical and clinical
      results.

PMID- 24591265
TI  - Pumping through porous hydrophobic/oleophilic materials: an alternative
      technology for oil spill remediation.
AB  - Recently, porous hydrophobic/oleophilic materials (PHOMs) have been shown to be
      the most promising candidates for cleaning up oil spills; however, due to their
      limited absorption capacity, a large quantity of PHOMs would be consumed in oil
      spill remediation, causing serious economic problems. In addition, the
      complicated and time-consuming process of oil recovery from these sorbents is
      also an obstacle to their practical application. To solve the above problems, we
      apply external pumping on PHOMs to realize the continuous collection of oil
      spills in situ from the water surface with high speed and efficiency. Based on
      this novel design, oil/water separation and oil collection can be simultaneously
      achieved in the remediation of oil spills, and the oil sorption capacity is no
      longer limited to the volume and weight of the sorption material. This novel
      external pumping technique may bring PHOMs a step closer to practical application
      in oil spill remediation. 

PMID- 24591266
TI  - Improved quality of surgical field during endoscopic sinus surgery after
      clonidine premedication--a pilot study.
AB  - BACKGROUND: Inadequate surgical field visualization due to intraoperative
      bleeding during endoscopic sinus surgery (ESS) can cause major complications. The
      aim of this prospective study was to compare the effect of preoperative
      administration of clonidine and melatonin on the quality of the surgical field
      visualization and selected aspects of presurgical premedication. METHODS: Twenty
      six patients undergoing ESS for chronic sinusitis and polyp removal were enrolled
      and randomly assigned to receive either oral clonidine or melatonin as
      preoperative premedication. During the operation, the quality of the surgical
      field was assessed and graded using the scale proposed by Boezaart. The
      evaluations were done at 15, 30, and 60 minutes after incision. The effect of
      this premedication choice on the intraoperative and postoperative hemodynamic
      profile was examined in each group. Anxiolytic effects of both premedication
      agents were assessed using the visual analogue scale for anxiety (VAS-A).
      Propofol dose and induction time (the time for bispectral index [BIS] to reach
      45), anesthesia and surgical procedures time, and recovery time (the time for BIS
      to reach 90) were assessed in both groups as well. RESULTS: The quality of the
      surgical field was consistently better in 2 of 3 time points in the clonidine
      group. Perioperative mean arterial pressure and intraoperative heart rate had a
      more favorable profile in patients premedicated with clonidine. There were no
      differences in other measured parameters between groups. CONCLUSION:
      Premedication with clonidine before ESS provides better quality of surgical field
      and more favorable hemodynamic profile as compared to melatonin.

PMID- 24591267
TI  - Metal-catalyzed annulation reactions for pi-conjugated polycycles.
AB  - The progress of the metal-catalyzed annulation reactions toward construction of
      various pi-conjugated polycyclic cores with high conjugation extension is
      described. This article gives a brief overview of various annulation reactions
      promoted by metal catalysts including C-H bond functionalization, [2+2+2]
      cycloaddition, cascade processes, ring closing metathesis, electrophilic
      aromatization, and various cross-coupling reactions. A variety of conjugated
      polycycles with planar, bowl-shaped, and helical structures have been constructed
      in high efficiency and selectivity.

PMID- 24591268
TI  - Oncocytic lipoadenoma of the parotid gland: cytological findings and differential
      diagnosis on fine-needle aspiration.
AB  - Oncocytic lipoadenoma is a rare benign neoplastic lesion of salivary gland. To
      the best of our knowledge, the detailed cytomorphological findings were described
      only in two cases. We are reporting a 56-year-old woman who presented with 1-year
      history of right parotid gland mass. Cytologic examination revealed tight
      clusters of bland looking oncocytic ductal cells with few aggregates of mature
      adipose tissue in a lipoid background and a benign oncocytic tumor of parotid
      gland was rendered. Histologically, a tumor with islands of oncocytic epithelial
      cells admixed with abundant mature adipose tissue was identified. Oncocytic
      lipoadenoma despite its rarity should be considered in the differential diagnosis
      of salivary gland fine-needle aspirations containing oncocytes especially those
      which are accompanied by mature adipose tissue and lipoid background.

PMID- 24591269
TI  - Paneth cell identification in the small intestine of guinea pig offsprings (Cavia
      porcellus).
AB  - The aim of this study was to determine the presence, number, and morphometrical
      characteristics of Paneth cells (PC) in the small intestine of guinea pigs during
      lactation. We used 48 pups from 0 to 15 days old. Samples from small intestine
      were fixed in 10% buffered formaldehyde (pH 7.4) and processed for histological
      and morphometrical studies using hematoxylin and eosin (HE), Phloxine tartrazine
      or Masson's Trichome staining, or immunohistochemistry for lysozyme. PC were
      morphologically identified at day 2 using Masson's Trichome or Phloxine
      tartrazine stainings, and at day 4 using HE, whereas using immunohistochemistry
      they were recognized from birth. Morphometrical differences were found between
      the intestinal sections at each age studied, and within each section during the
      first weeks of life. In all developmental stage, the highest number of PC was
      observed in the duodenum of 13 days old guinea pigs. Our results confirm the
      presence of PC in the small intestine of guinea pigs from birth.

PMID- 24591270
TI  - Progression of right ventricular dilation in repaired tetralogy of Fallot.
AB  - PURPOSE: To evaluate factors associated with rapid rate of progression (ROP) of
      right ventricular (RV) dilation by cardiac MRI in repaired tetralogy of Fallot
      (TOF) patients. MATERIALS AND METHODS: All patients with repaired TOF with two
      MRIs were included. RV volumes and function were assessed by MRIs performed on a
      GE 1.5 Tesla (T) platform. The ROP of RV dilation was calculated as the
      difference between the last and first RV indexed end-diastolic volumes (iEDV)
      divided by the time difference. Subjects were divided into two groups: Group I
      rapid ROP (top quartile of ROP) and Group II-slower ROP (lower three quartiles).
      RESULTS: A total of 61 subjects were included. Mean age was 18.0 +/- 9.7 years
      and duration between MRIs 3.4 +/- 2.1 years. Median ROP for RV iEDV was 2.0 (
      12.7 to 27.8) mL/m(2) /year. Fifteen subjects were in Group I and 46 in Group II.
      RV iEDV, RV ejection fraction, RV indexed end-systolic volume (iESV) were
      significantly different between groups. By multivariable analysis, RV iESV was
      the only independent parameter associated with rapid RV dilation (P < 0.01).
      CONCLUSION: There was no significant change in RV iEDV in majority of repaired
      TOF subjects. RV iESV was the best parameter associated with more rapid RV
      dilation.

PMID- 24591272
TI  - Opportune timing for palliative care specialty designation.

PMID- 24591271
TI  - Patterns of structural dynamics in RACK1 protein retained throughout evolution: a
      hydrogen-deuterium exchange study of three orthologs.
AB  - RACK1 is a member of the WD repeat family of proteins and is involved in multiple
      fundamental cellular processes. An intriguing feature of RACK1 is its ability to
      interact with at least 80 different protein partners. Thus, the structural
      features enabling such interactomic flexibility are of great interest. Several
      previous studies of the crystal structures of RACK1 orthologs described its
      detailed architecture and confirmed predictions that RACK1 adopts a seven-bladed
      beta-propeller fold. However, this did not explain its ability to bind to
      multiple partners. We performed hydrogen-deuterium (H-D) exchange mass
      spectrometry on three orthologs of RACK1 (human, yeast, and plant) to obtain
      insights into the dynamic properties of RACK1 in solution. All three variants
      retained similar patterns of deuterium uptake, with some pronounced differences
      that can be attributed to RACK1's divergent biological functions. In all cases,
      the most rigid structural elements were confined to B-C turns and, to some
      extent, strands B and C, while the remaining regions retained much flexibility.
      We also compared the average rate constants for H-D exchange in different regions
      of RACK1 and found that amide protons in some regions exchanged at least 1000
      fold faster than in others. We conclude that its evolutionarily retained
      structural architecture might have allowed RACK1 to accommodate multiple
      molecular partners. This was exemplified by our additional analysis of yeast
      RACK1 dimer, which showed stabilization, as well as destabilization, of several
      interface regions upon dimer formation. 

PMID- 24591273
TI  - Less is more: improving outcomes and cutting costs to Quebec's assisted
      reproduction program.

PMID- 24591274
TI  - UK proposes ban on smoking in cars carrying children.

PMID- 24591275
TI  - Salon. Sober second thought on Canadian health care.

PMID- 24591277
TI  - Strong.

PMID- 24591276
TI  - Sleep apnea and risk of pneumonia: a nationwide population-based study.
AB  - BACKGROUND: Evidence evaluating the risk of pneumonia in patients with
      obstructive sleep apnea is limited and mostly focuses on patients who receive
      continuous positive airway pressure (CPAP) therapy or on pediatric patients. We
      aimed to explore the risk of incident pneumonia among adults with sleep apnea,
      either with or without the need of CPAP therapy. METHODS: From Jan. 1, 2000, we
      identified adult patients with sleep apnea from the Taiwan National Health
      Insurance Research Database. A control cohort without sleep apnea, matched for
      age, sex and comorbidities, was selected for comparison. The 2 cohorts were
      followed until Dec. 31, 2010, and observed for occurrence of pneumonia. RESULTS:
      Of the 34,100 patients (6816 study patients and 27,284 matched controls), 2757
      (8.09%) had pneumonia during a mean follow-up period of 4.50 years, including 638
      (9.36%) study patients and 2119 (7.77%) controls. Kaplan-Meier analysis showed a
      higher incidence of pneumonia among patients with sleep apnea (log rank test, p <
      0.001). After multivariate adjustment, patients with sleep apnea experienced a
      1.20-fold (95% confidence interval 1.10-1.31) increase in incident pneumonia. The
      risk was even higher among patients who received CPAP therapy. INTERPRETATION:
      Sleep apnea appeared to confer a higher risk for future pneumonia, possibly in a
      severity-dependent manner.

PMID- 24591279
TI  - Graduated compression stockings.

PMID- 24591280
TI  - Anaphylaxis in the acute care setting.

PMID- 24591281
TI  - Low rates of immunity in adults behind H1N1 resurgence.

PMID- 24591282
TI  - Quebec will lose doctors if secular charter becomes law.

PMID- 24591283
TI  - Inside grey walls: unprepared for an aging inmate population.

PMID- 24591284
TI  - Hemorrhagic pustules in an Aboriginal man.

PMID- 24591285
TI  - Synthesis of tetracycline-imprinted polymer microspheres by reversible addition
      fragmentation chain-transfer precipitation polymerization using polyethylene
      glycol as a coporogen.
AB  - Tetracycline (TC)-imprinted microspheres have been synthesized by reversible
      addition-fragmentation chain-transfer precipitation polymerization using PEG as a
      coporogen. In the synthesis, methacrylic acid and ethylene dimethacrylate were
      used as the functional monomer and cross-linker, respectively. 2,2'
      Azobisisobutyronitrile was the initiator, and cumyl dithiobenzoate was the chain
      transfer reagent. Although monodispersed microspheres were obtained using
      acetonitrile as porogen, the particles cannot be used in the column extraction
      because of the high backpressure. To increase the porosity of the material, PEG
      was introduced as a coporogen. The influence of the molecular weight and
      concentration of PEG on the morphology, binding affinity, and porosity of the
      molecularly imprinted polymers (MIPs) have been studied. The results demonstrated
      that PEG as a macroporogen increased the porosity of the polymers. Meanwhile, the
      column backpressure was reduced using the MIPs with higher porosity. The binding
      affinity of the MIPs was increased when a low concentration of PEG was employed,
      while it was decreased when the ratio of PEG 12,000/monomers was >0.8%. Under the
      optimized conditions, TC-imprinted microspheres with good selectivity and size
      uniformity have been obtained, which facilitates its application in the column
      extraction for TC determinations.

PMID- 24591286
TI  - Composite materials for thermal energy storage: enhancing performance through
      microstructures.
AB  - Chemical incompatibility and low thermal conductivity issues of molten-salt-based
      thermal energy storage materials can be addressed by using microstructured
      composites. Using a eutectic mixture of lithium and sodium carbonates as molten
      salt, magnesium oxide as supporting material, and graphite as thermal
      conductivity enhancer, the microstructural development, chemical compatibility,
      thermal stability, thermal conductivity, and thermal energy storage performance
      of composite materials are investigated. The ceramic supporting material is
      essential for preventing salt leakage and hence provides a solution to the
      chemical incompatibility issue. The use of graphite gives a significant
      enhancement on the thermal conductivity of the composite. Analyses suggest that
      the experimentally observed microstructural development of the composite is
      associated with the wettability of the salt on the ceramic substrate and that on
      the thermal conduction enhancer. 

PMID- 24591287
TI  - Nitrogen uptake over entire root systems of tree seedlings.
AB  - Uptake of nitrogen (N) by sequential root regions in six tree species was
      measured in roots of 16- to 26-month-old seedlings at 50 and 1500 uM NH4NO3
      concentration, at the cell level using oscillating microelectrodes and at the
      root region level using enriched (15)N application. Our objective was to
      determine the root regions making the greatest contribution to total N uptake in
      each species as measured by the two contrasting techniques. White and condensed
      tannin zones were the regions with the smallest surface area in all species, but
      these zones often had the highest net flux of NH4(+) and NO3(-). For most
      species, little variation was found among root regions in N flux calculated using
      a (15)N mass balance approach, but where significant differences existed, high N
      flux was observed in white, cork or woody zones. When N fluxes measured by each
      of the two methods were multiplied by the estimated surface area or biomass of
      each root region, the effect of root region size had the greatest influence on
      regional N uptake. Root regions of greatest overall N uptake were the cork and
      woody zones, on average. Total N uptake may thus be greatest in older regions of
      tree seedling roots, despite low rates of uptake per unit area. 

PMID- 24591288
TI  - Research and publication trends in hospital medicine.
AB  - BACKGROUND: Research by hospitalists may aid the evolution of hospital medicine
      into an academic specialty. OBJECTIVE: To describe the factors associated with
      research and publication activities among hospitalists and describe trends in
      hospitalist-led publications. METHODS: We surveyed members of the Society of
      Hospital Medicine in June 2012 and conducted univariate analyses on their
      responses to determine predictors of successful authorship and to describe
      factors associated with research engagement. We searched PubMed from the database
      inception to October 2013 for publications with "hospitalist" or "hospital
      medicine" affiliated authors. Original research articles were reviewed for
      methodology and funding sources. RESULTS: Of the 645 respondents (5.8% response
      rate), 277 (43%) had authored peer-reviewed publications, 126 (19%) had access to
      mentorship, and 68 (11%) reported funding support. There were 213 (33%) who were
      engaged in research, with the majority conducting quality improvement (QI)
      research (n = 152, 24%). Completion of a fellowship, pediatrics training, the
      presence of a mentor, funding, and >25% protected time for research were each
      individually associated with an increased likelihood of authoring publications.
      Hospitalist-led publications in PubMed have been increasing from 36 in 2006 to
      179 in the first 10 months of 2013. Of the original research publications (n =
      317), the majority were clinical (n = 129, 41%), and 58 (18%) were QI. Thirty
      nine (22%) authors reported funding support. CONCLUSIONS: Peer-reviewed
      publications by hospitalists are increasing, suggesting the academic maturation
      of hospital medicine. Provision of mentorship for hospitalists specifically in QI
      and guidance toward funding resources may assist in supporting this trend.

PMID- 24591289
TI  - Targeting epigenetics in drug discovery.

PMID- 24591292
TI  - Juvenile ossifying fibroma diagnosed on fine needle aspiration cytology: a
      diagnostic challenge.
AB  - Preoperative diagnosis of jaw lesions is not always possible on the basis of
      clinico-radiological findings alone and needs to be confirmed before attempting
      any surgical intervention. Fibro-osseous lesions of the jaw comprise a spectrum
      of diseases which include cement-osseous dysplasia, fibrous dysplasia, and
      ossifying fibroma. The cytomorphological distinction between these individual
      entities is difficult. We present a case of maxillary fibro-osseous lesion in an
      adolescent girl diagnosed and categorized as juvenile ossifying fibroma
      preoperatively on cytology and confirmed on histopathology. Although aspirates
      are usually paucicellular in fibro-osseous lesions, certain cytological features
      if present in cellular cytosmears can offer further categorization and a
      definitive diagnosis may be possible in light of clinico-radiological
      correlation.

PMID- 24591294
TI  - Rhodium-catalyzed sequential allylic amination and olefin hydroacylation
      reactions: enantioselective synthesis of seven-membered nitrogen heterocycles.
AB  - Dynamic kinetic asymmetric amination of branched allylic acetimidates has been
      applied to the synthesis of 2-alkyl-dihydrobenzoazepin-5-ones. These seven
      membered-ring aza ketones are prepared in good yield with high enantiomeric
      excess by rhodium-catalyzed allylic substitution with 2-amino aryl aldehydes
      followed by intramolecular olefin hydroacylation of the resulting alkenals. This
      two-step procedure is amenable to varied functionality and proves useful for the
      enantioselective preparation of these ring systems. 

PMID- 24591293
TI  - Nanoscale adhesion forces between enamel pellicle proteins and hydroxyapatite.
AB  - The acquired enamel pellicle (AEP) is important for minimizing the abrasion
      caused by parafunctional conditions as they occur, for instance, during bruxism.
      It is a remarkable feature of the AEP that a protein/peptide film can provide
      enough protection in normofunction to prevent teeth from abrasion and wear.
      Despite its obvious critical role in the protection of tooth surfaces, the
      essential adhesion features of AEP proteins on the enamel surface are poorly
      characterized. The objective of this study was to measure the adhesion force
      between histatin 5, a primary AEP component, and hydroxyapatite (HA) surfaces.
      Both biotinylated histatin 5 and biotinylated human serum albumin were allowed to
      adsorb to streptavidin-coated silica microspheres attached to atomic force
      microscope (AFM) cantilevers. A multimode AFM with a Nanoscope IIIa controller
      was used to measure the adhesion force between protein-functionalized silica
      microspheres attached to cantilever tips and the HA surface. The imaging was
      performed in tapping mode with a Si3N4 AFM cantilever, while the adhesion forces
      were measured in AFM contact mode. A collection of force-distance curves
      (~3,000/replicate) was obtained to generate histograms from which the adhesion
      forces between histatin 5 or albumin and the HA surface were measured. We found
      that histatin 5 exhibited stronger adhesion forces (90% >1.830 nN) to the HA
      surface than did albumin (90% > 0.282 nN). This study presents an objective
      approach to adhesion force measurements between histatin 5 and HA, and provides
      the experimental basis for measuring the same parameters for other AEP
      constituents. Such knowledge will help in the design of synthetic proteins and
      peptides with preventive and therapeutic benefits for tooth enamel. 

PMID- 24591295
TI  - BMP4/Smad signaling pathway induces the differentiation of mouse spermatogonial
      stem cells via upregulation of Sohlh2.
AB  - Spermatogonial stem cells (SSCs) capable of self-renewal and differentiation are
      the foundation for spermatogenesis. Although several factors that govern these
      processes have been investigated, the underlying molecular mechanisms have not
      been fully elucidated. Here, we investigated the role of BMP4 in mouse SSC
      differentiation, and found that SSCs cultured in the presence of BMP4 underwent
      differentiation, characterized by downregulation of SSC self-renewal markers,
      Plzf, and upregulation of SSC differentiation marker, c-kit. Smad1/5/8 proteins
      were phosphorylated during BMP4-induced differentiation. The effects of BMP4 on
      SSCs were blocked by BMP4 inhibitor (Dorsomorphin). The activation of BMP4/Smad
      signaling pathway in SSCs increased the expression of Sohlh2, which is involved
      in the early differentiation of spermatogonia. Knockdown sohlh2 expression by RNA
      interference abolished the effect of BMP4 on SSC differentiation and the
      upregulation of c-kit expression. Overall, our results suggest that BMP4 plays an
      important role during the early differentiation of SSCs via upregulation of
      sohlh2.

PMID- 24591296
TI  - Impact of intranasal sodium hyaluronate on the short-term quality of life of
      patients undergoing functional endoscopic sinus surgery for chronic
      rhinosinusitis.
AB  - BACKGROUND: Functional endoscopic sinus surgery (FESS) has become the treatment
      of choice for patients with medically resistant chronic rhinosinusitis (CRS) and
      nasal polyps. Despite the consolidated use of different treatments, the
      postoperative period is often very painful and uncomfortable, especially during
      the first month. Although evidence on the effectiveness of sodium hyaluronate
      (SH) on postoperative care following FESS is available, data on the quality of
      life (QoL) from the patients' perspective are still lacking. This study aimed to
      evaluate for the first time the effectiveness of nasal douche with SH in reducing
      patients' discomfort during the first month following FESS. METHODS: A double
      blind randomized controlled study was carried out on 124 subjects undergoing FESS
      for CRS with nasal polyposis. They were divided into 2 groups: group I was
      treated with nasal douche containing 9 mg of high molecular weight SH plus saline
      solution and group II was treated with saline solution alone. To assess QoL in
      CRS patients, the Short Form-36 (SF-36) test, the Sino-Nasal Outcome Test-22
      (SNOT-22), and the visual analogue scale (VAS) questionnaires were administered.
      RESULTS: At baseline, there were no statistically significant differences between
      the 2 groups. However, after 30 days of long postoperative treatments, we found
      clinically significant improvements in QoL of subjects treated with SH, as
      evidenced by all QoL scales. CONCLUSION: Our data indicate that SH significantly
      improves patients' short-term QoL following FESS in terms of both general health
      and specific sinonasal status.

PMID- 24591297
TI  - History effects in lithium-oxygen batteries: how initial seeding influences the
      discharge capacity.
AB  - In laboratory experiments, Li-O2 systems show "sudden death" at capacities far
      below the theoretical value. Identifying how discharge products limit the total
      capacity is crucial in Li-O2 system. We investigated the effect of Li2O2 seed
      layer deposited on carbon cathode under potentiostatic conditions at increasing
      overpotentials to the subsequent slow discharge at galvanostatic condition. The
      discharge capacity attainable in the second step is found to vary by more than a
      factor of 3 depending on the history, i.e., the seed layer. These results provide
      evidence that the battery history is decisive for the total discharge capacities.

PMID- 24591298
TI  - Chemomic and chemometric approach based on ultra-fast liquid chromatography with
      ion trap time-of-flight mass spectrometry to reveal the difference in the
      chemical composition between Da-Cheng-Qi decoction and its three constitutional
      herbal medicines.
AB  - Da-Cheng-Qi decoction (DCQT) is a traditional purgative Chinese decoction with a
      history of 2000 years. To study the effect of interactions between the
      ingredients on the overall chemical composition of DCQT, a chemomic and
      chemometric approach based on ultra-fast liquid chromatography with ion trap time
      of-flight mass spectrometry was developed and validated. After mixing and
      decocting all four ingredients to make the DCQT, the concentrations of some
      chemicals are significantly different from those in single herb decoction and 24
      of them were identified and tentatively characterized by comparing their data
      with those of standard compounds or literature data. No new chemicals were formed
      during mixing and decoction. Our findings indicated that there are interactions
      between these natural medicines during the mixing and preparation process. The 24
      identified chemicals could be used as chemical markers for optimizing
      prescription and evaluation of consistent quality, and the strategy in the
      present study could be applied for other multiherb formulae. 

PMID- 24591299
TI  - It's safety, not the score, that needs improvement.

PMID- 24591300
TI  - Needle tract seeding: an avoidable complication.
AB  - Needle tract seeding refers to implantation of tumor cells by contamination when
      instruments like biopsy needles are used to examine, excise or ablate a tumor.
      Implantation along needle tract may lead to change of stage of the tumor,
      converting a resectable tumor into an inoperable one. In this paper we have
      reviewed the cases of needle tract seeding due to fine needle aspiration cytology
      (FNAC) procedure. We analyzed the various aspects of needle tract seedling and
      suggested how to take precautionary measures to prevent it.

PMID- 24591302
TI  - Binding kinetics of ZM241385 derivatives at the human adenosine A2A receptor.
AB  - Classical drug design and development rely mostly on affinity- or potency-driven
      structure-activity relationships (SAR). Thus far, a given compound's binding
      kinetics have been largely ignored, the importance of which is now being
      increasingly recognized. In the present study, we performed an extensive
      structure-kinetics relationship (SKR) study in addition to a traditional SAR
      analysis at the adenosine A2A receptor (A2A R). The ensemble of 24 A2A R
      compounds, all triazolotriazine derivatives resembling the prototypic antagonist
      ZM241385 (4-(2-((7-amino-2-(furan-2-yl)-[1,2,4]triazolo[1,5-a][1,3,5]triazin-5
      yl)amino)ethyl)phenol), displayed only minor differences in affinity, although
      they varied substantially in their dissociation rates from the receptor. We
      believe that such a combination of SKR and SAR analyses, as we have done with the
      A2A R, will have general importance for the superfamily of G protein-coupled
      receptors, as it can serve as a new strategy to tailor the interaction between
      ligand and receptor.

PMID- 24591303
TI  - Cationic chains of phosphanyl- and arsanylboranes.
AB  - Whilst catena-phosphorus cations have been intensively studied in the last years,
      mixed Group 13/15 element cationic chains have not yet been reported. Reaction of
      the pnictogenboranes H2EBH2?NMe3 (E=P, As) with monohalideboranes lead to the
      cationic chain compounds [Me3N?BH2EH2BH2?NMe3][X] (E=P, As; X=AlCl4 , I) and
      [Me3N?BH2PH2BH2PH2BH2?NMe3][X] (X=I, VCl4(thf)2), respectively. All of the
      compounds have been characterized by X-ray structure analysis, NMR spectroscopy,
      IR spectroscopy, and mass spectrometry. DFT calculations elucidate the reaction
      pathway, the high thermodynamic stability, the charge distribution within the
      chain and confirm the observed solid-state structures.

PMID- 24591301
TI  - Contribution of hydrogen bonds to protein stability.
AB  - Our goal was to gain a better understanding of the contribution of the burial of
      polar groups and their hydrogen bonds to the conformational stability of
      proteins. We measured the change in stability, Delta(DeltaG), for a series of
      hydrogen bonding mutants in four proteins: villin headpiece subdomain (VHP)
      containing 36 residues, a surface protein from Borrelia burgdorferi (VlsE)
      containing 341 residues, and two proteins previously studied in our laboratory,
      ribonucleases Sa (RNase Sa) and T1 (RNase T1). Crystal structures were determined
      for three of the hydrogen bonding mutants of RNase Sa: S24A, Y51F, and T95A. The
      structures are very similar to wild type RNase Sa and the hydrogen bonding
      partners form intermolecular hydrogen bonds to water in all three mutants. We
      compare our results with previous studies of similar mutants in other proteins
      and reach the following conclusions. (1) Hydrogen bonds contribute favorably to
      protein stability. (2) The contribution of hydrogen bonds to protein stability is
      strongly context dependent. (3) Hydrogen bonds by side chains and peptide groups
      make similar contributions to protein stability. (4) Polar group burial can make
      a favorable contribution to protein stability even if the polar groups are not
      hydrogen bonded. (5) The contribution of hydrogen bonds to protein stability is
      similar for VHP, a small protein, and VlsE, a large protein. 

PMID- 24591304
TI  - Significant SNPs have limited prediction ability for thyroid cancer.
AB  - Recently, five thyroid cancer significantly associated genetic variants
      (rs965513, rs944289, rs116909374, rs966423, and rs2439302) have been discovered
      and validated in two independent GWAS and numerous case-control studies, which
      were conducted in different populations. We genotyped the above five single
      nucleotide polymorphisms (SNPs) in Han Chinese populations and performed thyroid
      cancer-risk predictions with nine machine learning methods. We found that four
      SNPs were significantly associated with thyroid cancer in Han Chinese population,
      while no polymorphism was observed for rs116909374. Small familial relative risks
      (1.02-1.05) and limited power to predict thyroid cancer (AUCs: 0.54-0.60)
      indicate limited clinical potential. Four significant SNPs have limited
      prediction ability for thyroid cancer.

PMID- 24591305
TI  - Clinicopathological and ultrasonographic features of cats with eosinophilic
      enteritis.
AB  - Eosinophilic enteritis (EE) in cats is poorly characterized. The aim of the
      current study was to retrospectively evaluate the clinical and ultrasonographic
      findings in cats with histologic evidence of eosinophilic inflammation on
      gastrointestinal biopsy. Twenty-five cats with tissue eosinophilia on surgical
      (10) or endoscopic (15) biopsy of the gastrointestinal tract, having an abdominal
      ultrasound performed within 48 h of biopsy acquisition, were enrolled. History,
      clinical presentation, clinical pathology and abdominal ultrasound findings were
      reviewed. Intestinal biopsies were evaluated by a single pathologist and
      separated into two groups based on the degree of eosinophilic infiltrate: mild
      (<10 eosinophils/high-power field [HPF], 11/25 cats), or moderate/marked (>10
      eosinophils/HPF, 14/25 cats). The former were considered primary
      lymphoplasmacytic or lymphocytic inflammatory bowel disease (LPE) with subtle
      eosinophilic infiltrates, and the latter to have EE. Signalment, history and
      clinical signs were similar in all cats. Only cats with EE (6/14) had palpably
      thickened intestines. The only distinguishing clinicopathological feature of cats
      with EE was the presence of peripheral eosinophilia (6/14). On ultrasound, when
      compared with cats with LPE, cats with EE had a greater mean jejunal wall
      thickness (3.34 mm +/- 0.72 mm vs 4.07 mm +/- 0.58 mm, respectively) and an
      increased incidence of thickening of the muscularis layer (1/11 and 11/14,
      respectively). In conclusion, ultrasonographic evidence of a prominent intestinal
      muscularis layer, palpably thickened intestines and peripheral eosinophilia can
      serve as biomarkers for the presence of EE in cats with chronic intestinal signs.

PMID- 24591306
TI  - Photodeposition of copper and chromia on gallium oxide: the role of co-catalysts
      in photocatalytic water splitting.
AB  - Split second: The photocatalytic activity of gallium oxide (beta-Ga2 O3) depends
      strongly on the co-catalysts CuOx and chromia, which can be efficiently deposited
      in a stepwise manner by photoreduction of Cu(2+) and CrO4 (2-). The water
      splitting activity can be tuned by varying the Cu loading in the range 0.025-1.5
      wt %, whereas the Cr loading is not affecting the rate as long as small amounts
      (such as 0.05 wt %) are present. Chromia is identified as highly efficient co
      catalyst in the presence of CuOx : it is essential for the oxidation of water.

PMID- 24591307
TI  - Eye size and visual acuity influence vestibular anatomy in mammals.
AB  - The semicircular canals of the inner ear detect head rotations and trigger
      compensatory movements that stabilize gaze and help maintain visual fixation.
      Mammals with large eyes and high visual acuity require precise gaze stabilization
      mechanisms because they experience diminished visual functionality at low
      thresholds of uncompensated motion. Because semicircular canal radius of
      curvature is a primary determinant of canal sensitivity, species with large canal
      radii are expected to be capable of more precise gaze stabilization than species
      with small canal radii. Here, we examine the relationship between mean
      semicircular canal radius of curvature, eye size, and visual acuity in a large
      sample of mammals. Our results demonstrate that eye size and visual acuity both
      explain a significant proportion of the variance in mean canal radius of
      curvature after statistically controlling for the effects of body mass and
      phylogeny. These findings suggest that variation in mean semicircular canal
      radius of curvature among mammals is partly the result of selection for improved
      gaze stabilization in species with large eyes and acute vision. Our results also
      provide a possible functional explanation for the small semicircular canal radii
      of fossorial mammals and plesiadapiforms.

PMID- 24591308
TI  - Zirconia--a stationary phase capable of the separation of polar markers of
      myocardial metabolism in hydrophilic interaction chromatography.
AB  - Creatine, phosphocreatine, and adenine nucleotides are highly polar markers of
      myocardial metabolism that are poorly retained on RP silica sorbents. Zirconia
      represents an alternative material to silica with high promise to be used in
      hydrophilic interaction chromatography (HILIC). This study describes a first
      systematic investigation of the ability of ZrO2 to separate creatine,
      phosphocreatine, adenosine 5'-monophosphate, adenosine 5'-diphosphate, and
      adenosine 5'-triphosphate and compares the results with those obtained on TiO2 .
      All analytes showed a HILIC-like retention pattern when mobile phases of
      different strengths were tested. Stronger retention and better column performance
      were achieved in organic-rich mobile phases as compared to aqueous conditions,
      where poor retention and insufficient column performance were observed. The
      effect of mobile phase pH and ionic strength was evaluated as well. The analysis
      of myocardial tissue demonstrated that all compounds were separated in a relevant
      biological material and thus proved ZrO2 as a promising phase for HILIC of
      biological samples that deserves further investigation. 

PMID- 24591309
TI  - Chemical constituents and biological activities of Adenium obesum (Forsk.) Roem.
      et Schult.

PMID- 24591310
TI  - Chemical constituents of the plants from the genus Oplopanax.

PMID- 24591311
TI  - Fishing for accessory binding sites at GPCRs with 'loop-hooks' - an approach
      towards selectivity? Part I.
AB  - Receptor-subtype selectivity is an important issue in medicinal chemistry and can
      become very difficult to achieve if the actual binding pockets of the respective
      receptors are highly conserved. For such cases, known unselective ligands could
      be equipped with a spacer that sticks outside the actual orthosteric binding
      pocket towards the extracellular loops. The end of the spacer bears certain
      functional groups to enable specific or unspecific interactions with the receptor
      residues outside the binding cavity. Our experiments indicated that it is
      possible to achieve selectivity within the dopamine D1 family with such 'loop
      hooks'. 

PMID- 24591312
TI  - On dioxygen permeation through a dehydrogenase-pyrroloquinoline quinone complex.
      A molecular-dynamics investigation.
AB  - In this work, an all atom model of the quinoprotein dehydrogenase PqqC in complex
      with the PQQ (=4,5-dihydro-4,5-dioxo-1H-pyrrolo[2,3-f]quinoline-2,7,9
      tricarboxylic acid) cofactor and dioxygen (O2 ), solvated with TIP3 water in
      periodic boxes, was subjected to random-acceleration molecular dynamics (RAMD).
      It was found that O2 leaves the active binding pocket, in front of PQQ, to get to
      the solvent, as easily as with a variety of other O2 -activating enzymes, O2
      carriers, and gas-sensing proteins. The shortest pathway, orthogonal to the
      center of the mean plane of PQQ, was largely preferred by O2 over pathways
      slightly deviating from this line. These observations challenge the
      interpretation of an impermeable active binding pocket of PqqC-PQQ, as drawn from
      both X-ray diffraction data of the crystal at low temperature and physiological
      experimentation. 

PMID- 24591313
TI  - Nucleolipids of the cancerostatic 5-fluorouridine: synthesis, adherence to
      oligonucleotides, and incorporation in artificial lipid bilayers.
AB  - 5-Fluorouridine (1a) was converted to its N(3)-farnesylated nucleoterpene
      derivative 8 by direct alkylation with farnesyl bromide (4). Reaction of the
      cancerostatic 1a with either acetone, heptan-4-one, nonadecan-10-one, or
      hentriacontan-16-one afforded the 2',3'-O-ketals 2a-2d. Compound 2b was then
      first farnesylated (->5) and subsequently phosphitylated to give the
      phosphoramidite 6. The ketal 2c was directly 5'-phosphitylated without
      farnesylation of the base to give the phosphoramidite 7. Moreover, the recently
      prepared cyclic 2',3'-O-ketal 11 was 5'-phosphitylated to yield the
      phosphoramidite 12. The 2',3'-O-isopropylidene derivative 2a proved to be too
      labile to be converted to a phosphoramidite. All novel derivatives of 1a were
      unequivocally characterized by NMR and UV spectroscopy and ESI mass spectrometry,
      as well as by elemental analyses. The lipophilicity of the phosphoramidite
      precursors were characterized by both their retention times in RP-18 HPLC and by
      calculated log P values. The phosphoramidites 6, 7, and 12 were exemplarily used
      for the preparation of four terminally lipophilized oligodeoxynucleotides
      carrying a cyanine-3 or a cyanine-5 residue at the 5'-(n-1) position (i.e., 14
      17). Their incorporation in an artificial lipid bilayer was studied by single
      molecule fluorescence spectroscopy and fluorescence microscopy. 

PMID- 24591314
TI  - Small cyclen-imidazolium-containing molecules and their interactions with DNA.
AB  - Three small organic molecules containing different numbers of cyclen and
      imidazolium units were synthesized. Their interactions with plasmid DNA and their
      potential for gene delivery vectors were investigated. Agarose gel retardation
      and ethidium bromide exclusion assays revealed that these molecules can
      effectively condense DNA, and compounds with higher molecular weights are needed
      to lower w/w ratio for full condensation. Dynamic light scattering (DLS) and
      transmission electron microscopy (TEM) indicated that these compounds may form
      nanosized spherical particles with DNA. Furthermore, the complex formed from 10,
      i.e., 10/DNA, can partially release DNA from compact state at a relatively higher
      concentration of NaCl (200 mM). In the presence of the lipid 1,2-dioleoyl-sn
      glycero-3-phosphoethanolamine (DOPE), 10 could transfer plasmid DNA into BEL-7402
      cells. In addition, these compounds exhibited much lower cytotoxicity than PEI 25
      kDa. 

PMID- 24591315
TI  - Characterization of secondary metabolites, biological activity and glandular
      trichomes of Stachys tymphaea Hausskn. from the Monti Sibillini National Park
      (Central Apennines, Italy).
AB  - Stachys tymphaea (Lamiaceae) is a perennial herb growing in forest openings and
      dry meadows of central and southern Italy. It was investigated for the first time
      here, determining the content of secondary metabolites, the micromorphology of
      glandular trichomes, the histochemical localization of secretion, and the
      biological activity of the volatile oil, namely, the cytotoxic, antioxidant, and
      antimicrobial properties. The plant showed a peculiar molecular pattern, being
      rich of biophenolic compounds as flavonoids, phenylethanoid glycosides, and
      caffeoylquinic acid derivatives, but poor of iridoids, which are known as marker
      compounds of the genus Stachys. The essential oil was characterized by GC-FID and
      GC/MS analyses, revealing a high percentage of sesquiterpene hydrocarbons
      (54.6%), with germacrene D (30.0%) and (E)-beta-farnesene (12.4%) as the most
      abundant compounds, while other main components were representatives of the
      diterpenes (19.2%), represented mainly by (E)-phytol (11.9%). This composition
      supported the taxonomic relationships in the genus Stachys, which comprises oil
      poor species producing essential oils rich in hydrocarbons, with germacrene D as
      one of the predominant components. The micromorphological study revealed three
      types of glandular hairs, i.e., Type A peltate trichomes, being the primary sites
      of essential oil biosynthesis, Type B short-stalked trichomes, typical
      mucopolysaccharide producers, and Type C long capitate trichomes, secreting a
      complex mixture of both lipophilic and hydrophilic substances, with a major
      phenolic fraction. Moreover, the MTT assay revealed the potential of the volatile
      oil to inhibit A375, HCT116, and MDA-MB 231 tumor cells lines (IC50 values of
      23.9-34.4 MUg/ml). 

PMID- 24591316
TI  - Limonoids with an oxygen bridge between C(1) and C(29) from the seeds of a
      Krishna mangrove, Xylocarpus granatum.
AB  - Ten limonoids, named granatumins L-U (1-10, resp.), were isolated from the seeds
      of an Indian mangrove, Xylocarpus granatum, collected in the estuary of Krishna,
      Andhra Pradesh. The structures of these compounds were established on the basis
      of spectroscopic data. The relative configuration of granatumin L (1) was
      confirmed by a single-crystal X-ray diffraction analysis. Granatumins L-T (1-9,
      resp.) belong to the small group of limonoids with an oxygen bridge between C(1)
      and C(29), while granatumin U (10) is a 28-Me-oxidized mexicanolide. This is the
      first report of limonoids with an O-bridge between C(1) and C(29) from the Indian
      X. granatum. The pronounced structural diversity of limonoids from this mangrove
      might originate from environmental factors. 

PMID- 24591317
TI  - Comprehensive study of the phenolics and saponins from Helleborus niger L. Leaves
      and stems by liquid chromatography/tandem mass spectrometry.
AB  - The aerial parts of the medicinal plant Helleborus niger L. comprise a
      substantial number of constituents with only few of them identified so far. To
      expand the knowledge of its secondary metabolite profile, extracts from H. niger
      leaves and stems were investigated by liquid chromatography/tandem mass
      spectrometry (LC/MS(n) ). Specific identification strategies using LC/MS are
      established and discussed in detail. The leaves turned out to contain acylated
      and non-acylated quercetin and kaempferol oligoglycosides, protoanemonin and its
      precursor ranunculin, beta-ecdysone, and a variety of steroidal saponins, mainly
      in the furostanol form. The sapogenins were elucidated as of sarsasapogenyl,
      diosgenyl, and macranthogenyl structures, and confirmed by comparison with the
      respective reference compounds. The secondary metabolite profiles were almost
      identical in both plant parts except that the stems lacked kaempferol derivatives
      and some saponins. The ranunculin derivatives and beta-ecdysone were found in
      both plant parts. Correlations between the location of the compound groups and
      the plant's defense strategies are proposed. Additionally, the role of the
      detected secondary metabolites as protective substances against exogenic stress
      and as a defense against herbivores is discussed. 

PMID- 24591318
TI  - Design, synthesis, lipophilic properties, and binding affinities of potential
      ligands in positron emission tomography (PET) for visualization of brain dopamine
      D4 receptors.
AB  - We report the synthesis of compounds structurally related to the high-affinity
      dopamine D4 receptor ligand N-{2-[4-(3-cyanopyridin-2-yl)piperazin-1-yl]ethyl}-3
      methoxybenzamide (1e). All compounds were specifically designed as potential PET
      radioligands for brain D4 receptor visualization, having lipophilicity within a
      range for brain uptake and weak non-specific binding (0.75<cLogP<3.15) and
      bearing a substituent for easy access to labeling with the positron emitter
      isotope (11) C or (18) F. The best compound of the series, N-{2-[4-(4
      chlorophenyl)piperazin-1-yl]ethyl}-6-fluoropyridine-3-carboxamide (7a), displayed
      excellent selectivity over D2 and D3 receptors (>100-fold), but its D4 receptor
      affinity was suboptimal for imaging of brain D4 receptors (Ki =30 nM). 

PMID- 24591319
TI  - Inhibition of NO production by Grindelia argentina and isolation of three new
      cytotoxic saponins.
AB  - A bioassay-guided phytochemical analysis of the ethanolic extract of Grindelia
      argentina Deble & Oliveira-Deble (Asteraceae) allowed the isolation of a known
      flavone, hispidulin, and three new oleanane-type saponins, 3-O-beta-D
      xylopyranosyl-(1->3)-beta-D-glucopyranosyl-2beta,3beta,16alpha,23
      tetrahydroxyolean-12-en-28-oic acid 28-O-beta-D-xylopyranosyl-(1->2)-beta-D
      apiofuranosyl-(1->3)-beta-D-xylopyranosyl-(1->3)-alpha-L-rhamnopyranosyl-(1->2)
      alpha-L-arabinopyranosyl ester (2), 3-O-beta-D-glucopyranosyl-2beta,3beta,23
      trihydroxyolean-12-en-28-oic acid 28-O-beta-D-xylopyranosyl-(1->2)-beta-D
      apiofuranosyl-(1->3)-beta-D-xylopyranosyl-(1->3)-alpha-L-rhamnopyranosyl-(1->2)
      alpha-L-arabinopyranosyl ester, (3) and 3-O-beta-D-xylopyranosyl-(1->3)-beta-D
      glucopyranosyl-2beta,3beta,23-trihydroxyolean-12-en-28-oic acid 28-O-beta-D
      xylopyranosyl-(1->2)-beta-D-apiofuranosyl-(1->3)-beta-D-xylopyranosyl-(1->3)
      alpha-L-rhamnopyranosyl-(1->2)-alpha-L-arabinopyranosyl ester (4), named
      grindeliosides A-C, respectively. Their structures were determined by extensive
      1D- and 2D-NMR experiments along with mass spectrometry and chemical evidence.
      The isolated compounds were evaluated for their inhibitory activities against
      LPS/IFN-gamma-induced NO production in RAW 264.7 macrophages and for their
      cytotoxic activities against the human leukemic cell line CCRF-CEM and MRC-5 lung
      fibroblasts. Hispidulin markedly reduced LPS/IFN-gamma-induced NO production
      (IC50 51.4 MUM), while grindeliosides A-C were found to be cytotoxic, with
      grindelioside C being the most active against both CCRF-CEM (IC50 4.2+/-0.1 MUM)
      and MRC-5 (IC50 4.5+/-0.1 MUM) cell lines. 

PMID- 24591320
TI  - Bark essential oil of Cedrelopsis grevei from Madagascar: investigation of steam
      distillation conditions.
AB  - The effect of the distillation time on the yield and chemical composition of the
      bark essential oil of Cedrelopsis grevei Baill. was investigated. Distillation
      kinetics were determined for three batches of bark sampled from two sites, i.e.,
      Itampolo (batches IT1 and IT2) and Salary (SAL), located in a region in the south
      of Madagascar with characteristically large populations of C. grevei. The bark
      samples were subjected to steam distillation, and the essential oil was collected
      at 3-h intervals. The total yield (calculated after 14 h of distillation) varied
      from 0.9 to 1.7%, according to the batch tested. Moreover, the essential oils
      obtained were characterized by GC-FID and GC/MS analyses. During the course of
      the distillation, the relative percentages of the most volatile components
      (monoterpenes and sesquiterpene hydrocarbons) diminished progressively, whereas
      the least volatile ones (oxygenated derivatives) increased at a consistent rate.
      Principal component analysis (PCA) and agglomerative hierarchical clustering
      analysis (AHC) of the results, performed on 13 principal components, allowed
      distinguishing three chemical groups, corresponding to the three batches,
      irrespective of the distillation time. This indicated that the chemical
      variability currently observed with commercial samples is not mainly linked to
      the experimental conditions of the extraction process, as the distillation time
      did not significantly alter the chemical composition of the essential oils. 

PMID- 24591322
TI  - Lasting legacies.

PMID- 24591321
TI  - Chemical variability of Xylopia quintasii Engl. & Diels leaf oil from Cote
      d'Ivoire.
AB  - The chemical composition of 42 essential-oil samples isolated from the leaves of
      Xylopia quintasii harvested in three Ivoirian forests was investigated by GC-FID,
      including the determination of retention indices (RIs), and by (13) C-NMR
      analyses. In total, 36 components accounting for 91.9-92.6% of the oil
      composition were identified. The content of the main components varied
      drastically from sample to sample: (E)-beta-caryophyllene (0.9-56.9%), (Z)-beta
      ocimene (0.3-54.6%), beta-pinene (0.8-27.9%), alpha-pinene (0.1-22.8%), and
      furanoguaia-1,4-diene (0.0-17.6%). The 42 oil compositions were submitted to
      hierarchical cluster and principal components analysis, which allowed the
      distinction of three groups within the oil samples. The composition of the oils
      of the major group (22 samples) was dominated by (E)-beta-caryophyllene. The oils
      of the second group (12 samples) contained beta-pinene and alpha-pinene as the
      principal compounds, while the oils of the third group (8 samples) were dominated
      by (Z)-beta-ocimene, germacrene D, (E)-beta-ocimene, and furanoguaia-1,4-diene.
      The oil samples of Group I and II came from clay-soil forests, while the oil
      samples belonging to Group III were isolated from leaves harvested in a sandy
      soil forest. 

PMID- 24591323
TI  - Special issue celebrating 40 years of the Mukaiyama aldol reaction: introductory
      remarks.

PMID- 24591327
TI  - The Nozoe Autograph Books: segment 9.

PMID- 24591328
TI  - Solution structure of lysine-free (K0) ubiquitin.
AB  - Lysine-free ubiquitin (K0-Ub) is commonly used to study the ubiquitin-signaling
      pathway, where it is assumed to have the same structure and function as wild-type
      ubiquitin (wt-Ub). However, the K0-Ub (15) N heteronuclear single quantum
      correlation NMR spectrum differs significantly from wt-Ub and the melting
      temperature is depressed by 19 degrees C, raising the question of the structural
      integrity and equivalence to wt-Ub. The three-dimensional structure of K0-Ub was
      determined by solution NMR, using chemical shift and residual dipolar coupling
      data. K0-Ub adopts the same backbone structure as wt-Ub, and all significant
      chemical shifts can be related to interactions impacted by the K to R mutations. 

PMID- 24591329
TI  - High-throughput synthesis of peptide alpha-thioesters: a safety catch linker
      approach enabling parallel hydrogen fluoride cleavage.
AB  - Peptide alpha-thioesters are fundamental building blocks in peptide and protein
      science, providing powerful tools for peptide medicinal chemistry. The
      application of peptide alpha-thioesters in native chemical ligation reactions has
      enabled synthetic access to cysteine-rich peptides and proteins, cyclic peptides
      as well as labeled and chemically modified biomolecules. An efficient high
      throughput synthesis of peptide alpha-thioester building blocks would be
      beneficial for many medicinal chemical applications that require peptides and
      proteins. Herein we present a novel synthetic route to cysteine-rich peptide
      alpha-thioesters using a safety catch linker that enables a parallel synthetic
      strategy for chemical protein synthesis. ACP(68-75), bradykinin and dynorphin(1
      13) were synthesized via Boc chemistry in their thioester form on a safety catch
      amide linker (SCAL), employing polystyrene- or poly(ethylene glycol)-based
      resins, compartmentalized in tea bags. This compartmentalized resin/linker
      strategy facilitated a parallel hydrogen fluoride cleavage in which each peptide
      thioester was subsequently cyclized by native chemical ligation, demonstrating
      the utility of this approach. A naturally occurring bioactive cyclic peptide, the
      sunflower trypsin inhibitor SFTI-1, was synthesized to demonstrate the viability
      of this method to access important peptide biomolecules. 

PMID- 24591330
TI  - Highly enantioselective kinetic resolution of axially chiral BINAM derivatives
      catalyzed by a Bronsted acid.
AB  - A highly efficient strategy for the kinetic resolution of axially chiral BINAM
      derivatives involving a chiral Bronsted acid-catalyzed imine formation and
      transfer hydrogenation cascade process was developed. The kinetic resolution
      provides a convenient route to chiral BINAM derivatives in high yields with
      excellent enantioselectivities. 

PMID- 24591332
TI  - Adjusted drug treatment is superior to renal sympathetic denervation in patients
      with true treatment-resistant hypertension.
AB  - We aimed to investigate for the first time the blood pressure (BP)-lowering
      effect of renal sympathetic denervation (RDN) versus clinically adjusted drug
      treatment in true treatment-resistant hypertension (TRH) after excluding patients
      with confounding poor drug adherence. Patients with apparent TRH (n=65) were
      referred for RDN, and those with secondary and spurious hypertension (n=26) were
      excluded. TRH was defined as office systolic BP (SBP) >140 mm Hg, despite
      maximally tolerated doses of >=3 antihypertensive drugs including a diuretic. In
      addition, ambulatory daytime SBP >135 mm Hg after witnessed intake of
      antihypertensive drugs was required, after which 20 patients had normalized BP
      and were excluded. Patients with true TRH were randomized and underwent RDN (n=9)
      performed with Symplicity Catheter System versus clinically adjusted drug
      treatment (n=10). The study was stopped early for ethical reasons because RDN had
      uncertain BP-lowering effect. Office SBP and diastolic BP in the drug-adjusted
      group changed from 160+/-14/88+/-13 mm Hg (+/-SD) at baseline to 132+/-10/77+/-8
      mm Hg at 6 months (P<0.0005 and P=0.02, SBP and diastolic BP, respectively) and
      in the RDN group from 156+/-13/91+/-15 to 148+/-7/89+/-8 mm Hg (P=0.42 and
      P=0.48, SBP and diastolic BP, respectively). SBP and diastolic BP were
      significantly lower in the drug-adjusted group at 6 months (P=0.002 and P=0.004,
      respectively), and absolute changes in SBP were larger in the drug-adjusted group
      (P=0.008). Ambulatory BPs changed in parallel to office BPs. Our data suggest
      that adjusted drug treatment has superior BP lowering effects compared with RDN
      in patients with true TRH. Clinical Trial Registration- URL:
      http://www.clinicaltrials.gov. Unique identifier: NCT01673516. 

PMID- 24591334
TI  - Optimum blood pressure target after lacunar stroke: con side of the argument.

PMID- 24591333
TI  - Endothelial dysfunction and enhanced contractility in microvessels from
      ovariectomized rats: roles of oxidative stress and perivascular adipose tissue.
AB  - Ovarian hormone loss increases reactive oxidative species, endothelial
      dysfunction, and cardiovascular disease. Because perivascular adipose tissue
      (PVAT) regulates endothelial function, we hypothesized that reactive oxidative
      species in PVAT mediate adverse microvascular effects of ovarian hormone
      deficiency. Rats were ovariectomized or sham operated and given vehicle or tempol
      for 6 weeks. Mesenteric resistance arterioles from ovariectomized compared with
      sham-operated rats had dysfunctional responses to acetylcholine (ACh) including
      decreased ACh-induced endothelium-dependent relaxation (50+/-6% versus 72+/-2%)
      and endothelium-dependent relaxation factor (17+/-4% versus 37+/-2%) and
      increased endothelium-dependent contracting factor (27+/-5% versus 9+/-3%). OVX
      rat mesenteric arterioles had increased contractions to the
      thromboxane/prostanoid receptor agonist U-46 619 (58+/-3% versus 40+/-5%) and
      increased reactive oxidative species (tempo-9-AC fluorescence) with U-46 619
      (0.65+/-0.17 versus 0.14+/-0.06 Delta unit) or ACh (0.49+/-0.09 versus 0.09+/
      0.05 Delta unit) and increased p22(phox) protein expression (0.89+/-0.05 versus
      0.18+/-0.04 Delta unit), whereas nitric oxide activity (DAF-FM [4-amino-5
      methylamino-2',7'-difluorofluorescein diacetate] fluorescence) with ACh was
      reduced (0.39+/-0.1 versus 0.70+/-0.10 Delta unit). No differences were found in
      endothelium-dependent hyperpolarizing factor or contractile responses to
      phenylephrine. PVAT enhanced ACh-induced relaxation, endothelium-dependent
      relaxation factor, and nitric oxide only in sham-operated rats. Tempol prevented
      ovariectomy-induced endothelial dysfunction and restored the enhancing effects of
      PVAT on ACh-induced relaxation, endothelium-dependent relaxation factor, and
      nitric oxide in ovariectomized rat vessels, but both tempol and PVAT were
      required to normalize the enhanced U-46 619 contractions after ovariectomy. In
      conclusion, ovariectomy redirects endothelial responses from relaxation to
      contraction by reducing vascular nitric oxide, augmenting thromboxane/prostanoid
      receptor signaling, and attenuating the vasodilatory effects of PVAT, all of
      which were dependent on reactive oxidative species. 

PMID- 24591335
TI  - Clinical effect of naturally random allocation to lower systolic blood pressure
      beginning before the development of hypertension.
AB  - Systolic blood pressure (SBP) rises approximately linearly with age in most
      societies. The cause of this rise is unclear. We tested the hypothesis that SBP
      is causally associated with the rate of rise in SBP with age by evaluating the
      effect of 12 polymorphisms associated with lower SBP on the age-related rate of
      rise in SBP in a series of meta-regression analyses involving <=199 477
      participants in 63 studies. We then evaluated the effect of these polymorphisms
      on the odds of coronary heart disease in 22,223 case and 64,762 control subjects
      and compared it with the effect of lower SBP observed in both prospective cohort
      studies and blood pressure-lowering randomized trials. All 12 polymorphisms were
      associated with both lower SBP and a slower age-related rise in SBP. The weighted
      mean effect of these 12 polymorphisms was associated with a 0.32-mm Hg lower SBP
      (P=1.79*10(-7)) and a 0.093-mm Hg/decade slower age-related rise in SBP
      (P=3.05*10(-5)). The effect of long-term exposure to lower SBP on coronary heart
      disease mediated by these polymorphisms was 2-fold greater than that observed in
      prospective cohort studies (P=0.006) and 3-fold greater than that observed in
      short-term blood pressure treatment trials (P=0.001). We conclude therefore that
      SBP seems to be causally associated with the rate of rise in SBP with age and has
      a cumulative effect on the risk of coronary heart disease.

PMID- 24591337
TI  - Clinical improvement and successful pregnancy in a preeclamptic patient with
      antiphospholipid syndrome treated with pravastatin.

PMID- 24591338
TI  - Optimum blood pressure target after lacunar stroke: pro side of the argument.

PMID- 24591336
TI  - Diastrophic dysplasia sulfate transporter (SLC26A2) is expressed in the adrenal
      cortex and regulates aldosterone secretion.
AB  - Elucidation of the molecular mechanisms leading to autonomous aldosterone
      secretion is a prerequisite to define potential targets and biomarkers in the
      context of primary aldosteronism. After a genome-wide association study with
      subjects from the population-based Cooperative Health Research in the Region of
      Augsburg F4 survey, we observed a highly significant association (P=6.78*10(-11))
      between the aldosterone to renin ratio and a locus at 5q32. Hypothesizing that
      this locus may contain genes of relevance for the pathogenesis of primary
      aldosteronism, we investigated solute carrier family 26 member 2 (SLC26A2), a
      protein with known transport activity for sulfate and other cations. Within
      murine tissues, adrenal glands showed the highest expression levels for SLC26A2,
      which was significantly downregulated on in vivo stimulation with angiotensin II
      and potassium. SLC26A2 expression was found to be significantly lower in
      aldosterone-producing adenomas in comparison with normal adrenal glands. In
      adrenocortical NCI-H295R cells, specific knockdown of SLC26A2 resulted in a
      highly significant increase in aldosterone secretion. Concomitantly, expression
      of steroidogenic enzymes, as well as upstream effectors including transcription
      factors such as NR4A1, CAMK1, and intracellular Ca(2+) content, was upregulated
      in knockdown cells. To substantiate further these findings in an SLC26A2 mutant
      mouse model, aldosterone output proved to be increased in a sex-specific manner.
      In summary, these findings point toward a possible effect of SLC26A2 in the
      regulation of aldosterone secretion potentially involved in the pathogenesis of
      primary aldosteronism. 

PMID- 24591339
TI  - Imatinib mesylate attenuates myocardial remodeling through inhibition of platelet
      derived growth factor and transforming growth factor activation in a rat model of
      hypertension.
AB  - Imatinib mesylate is a specific tyrosine kinase inhibitor that may block the
      platelet-derived growth factor and transforming growth factor pathways. These
      pathways are known to provoke fibroblast activation. We evaluated whether
      imatinib, by inhibiting these pathways, prevents diastolic dysfunction and
      attenuates myocardial remodeling using spontaneously hypertensive rats (SHRs).
      Eight-week-old male SHRs were randomly assigned to either imatinib treatment
      group (30 mg/kg per day; n=10; SHR-I) or hypertensive control group (distilled
      water, n=10; SHR-C). Wistar-Kyoto rats were used as normal controls (n=10). At 16
      weeks, all rats underwent hemodynamic studies and Doppler echocardiography and
      then were euthanized. Their hearts were extracted for histopathologic,
      immunoblotting, and quantitative reverse transcriptase polymerase chain reaction
      analyses. Although imatinib did not affect blood pressure, it markedly reduced
      perivascular and interstitial fibrosis in the hearts of SHR. Echocardiogram
      showed that imatinib significantly reduced the left ventricular wall thickness
      (septal/posterior wall; SHR-C versus SHR-I, 18+/-1/19+/-2 versus 15+/-1/15+/-1
      mm; P<0.001) and increased the E/A ratio (SHR-C versus SHR-I, 1.59+/-0.11 versus
      1.84+/-0.16; P=0.001). Also, imatinib significantly reduced the mRNA expression
      of collagen type I, III, and platelet-derived growth factor receptor-beta
      phosphorylation in the hearts of SHR. In addition, imatinib reduced collagen
      production by inhibiting the phosphorylation of c-abl and platelet-derived growth
      factor receptor-beta in rat cardiac fibroblasts. In conclusion, these results
      suggest that imatinib could attenuate myocardial remodeling and improve left
      ventricular diastolic dysfunction in a hypertensive rat model by affecting
      platelet-derived growth factor and transforming growth factor-beta1 pathway
      without the blood pressure-lowering effect. 

PMID- 24591340
TI  - In preeclampsia, maternal third trimester subcutaneous adipocyte lipolysis is
      more resistant to suppression by insulin than in healthy pregnancy.
AB  - Obesity increases preeclampsia risk, and maternal dyslipidemia may result from
      exaggerated adipocyte lipolysis. We compared adipocyte function in preeclampsia
      with healthy pregnancy to establish whether there is increased lipolysis.
      Subcutaneous and visceral adipose tissue biopsies were collected at caesarean
      section from healthy (n=31) and preeclampsia (n=13) mothers. Lipolysis in
      response to isoproterenol (200 nmol/L) and insulin (10 nmol/L) was assessed. In
      healthy pregnancy, subcutaneous adipocytes had higher diameter than visceral
      adipocytes (P<0.001). Subcutaneous and visceral adipocyte mean diameter in
      preeclampsia was similar to that in healthy pregnant controls, but cell
      distribution was shifted toward smaller cell diameter in preeclampsia. Total
      lipolysis rates under all conditions were lower in healthy visceral than
      subcutaneous adipocytes but did not differ after normalization for cell diameter.
      Visceral adipocyte insulin sensitivity was lower than subcutaneous in healthy
      pregnancy and inversely correlated with plasma triglyceride (r=-0.50; P=0.004).
      Visceral adipose tissue had lower ADRB3, LPL, and leptin and higher insulin
      receptor messenger RNA expression than subcutaneous adipose tissue. There was no
      difference in subcutaneous adipocyte lipolysis rates between preeclampsia and
      healthy controls, but subcutaneous adipocytes had lower sensitivity to insulin in
      preeclampsia, independent of cell diameter (P<0.05). In preeclampsia, visceral
      adipose tissue had higher LPL messenger RNA expression than subcutaneous. In
      conclusion, in healthy pregnancy, the larger total mass of subcutaneous adipose
      tissue may release more fatty acids into the circulation than visceral adipose
      tissue. Reduced insulin suppression of subcutaneous adipocyte lipolysis may
      increase the burden of plasma fatty acids that the mother has to process in
      preeclampsia. 

PMID- 24591342
TI  - Changes in highly sensitive alpha-fetoprotein for the prediction of the outcome
      in patients with hepatocellular carcinoma after hepatectomy.
AB  - We investigated changes in highly sensitive lens culinaris agglutinin A-reactive
      fraction of alpha-fetoprotein (hsAFP-L3) measured using a novel method and its
      predictive ability for prognosis in patients with hepatocellular carcinoma (HCC)
      who underwent curative hepatectomy, comparing to other HCC tumor markers, that
      is, AFP, des-gamma-carboxy prothrombin (DCP), and AFP-L3 measured with
      conventional method (cAFP-L3). AFP, DCP, and AFP-L3 including both cAFP-L3 and
      hsAFP-L3 were measured before and after curative hepatectomy in 187 patients. The
      percentage of patients with elevated tumor marker levels pre- and postoperatively
      was compared, and recurrence-free and overall survival rates were analyzed based
      on changes in tumor markers. The percentages of patients with elevated AFP, DCP,
      and cAFP-L3 decreased postoperatively. In contrast, the percentage of patients
      with elevated hsAFP-L3 did not decrease postoperatively. Both recurrence-free and
      overall survival rates were significantly lower in patients whose tumor marker
      levels remained elevated postoperatively than patients without tumor marker
      elevation postoperatively. Recurrence-free and overall survival rates of patients
      in whom hsAFP-L3 became elevated postoperatively despite normal preoperative
      hsAFP-L3 levels were significantly lower than those of patients with normal hsAFP
      L3 postoperatively, and were similar to those of patients with persistent
      elevation. Preoperative elevations of AFP, DCP, and cAFP normalized in many
      patients postoperatively, but not for hsAFP-L3. The elevation of hsAFP-L3
      identifies patients with poor prognosis despite the normalization of AFP and DCP.

PMID- 24591343
TI  - Preparation of monolithic fibers for the solid-phase microextraction of
      chlorophenols in water samples.
AB  - Monolithic fibers were synthesized and applied for the solid-phase
      microextraction and determination of chlorophenols in environmental water samples
      by coupling with HPLC. The fibers were prepared by copolymerization of
      vinylimidazole and ethylene dimethacrylate as functional monomer and cross
      linker, respectively. The effect of the preparation conditions of monolithic
      fibers on the extraction efficiencies was investigated in detail. Several
      characteristic techniques, such as elemental analysis, infrared spectroscopy,
      mercury-intrusion porosimetry, and SEM were used to characterize the monolithic
      material. The effect of the extraction parameters, including desorption solvent,
      extraction and desorption time, pH values, and ionic strength in sample matrix on
      the extraction performance was investigated thoroughly. Under the improved
      extraction conditions, the linear ranges of 2-chlorophenol, 2,4-dichlorophenol
      and pentachlorophenol were 1.0-200 MUg/L and 2.0-200 MUg/L for 2,4,6
      trichlorophenol. The detection limits (S/N = 3) were in the range of 0.16-0.45
      MUg/L, the RSDs for intraday and interday precisions were <7.0%. Finally, the
      proposed method was successfully used to detect different environmental water
      samples. The recoveries of spiked water samples were ranged from 90.0 to 115%. At
      the same time, satisfactory repeatability was achieved with RSDs < 9.0%. 

PMID- 24591344
TI  - Pregnancy-induced hypertension is associated with altered anatomical patterns of
      Hyrtl's anastomosis.
AB  - Umbilical arteries carry the blood from the fetus to the placenta and are
      typically connected by Hyrtl's anastomosis, a connection that is located near
      where the umbilical cord meets the placenta. The investigation of the anastomosis
      in pathological conditions, including pregnancy-induced hypertension is limited.
      Hence, 200 placenta and umbilical cords, 100 from normotensive and 100 from
      pregnancy-induced hypertensive subjects, were dissected and measurements were
      recorded. A single anastomosis between the umbilical arteries was observed in 167
      specimens. In 16 cases, the two umbilical arteries were fused, in 15 cases there
      was no anastomosis, and in two cases there was a single umbilical artery. In one
      specimen from a normotensive case, a double anastomosis was observed. To our
      knowledge this is only the second report of this rare anatomical variant. When an
      anastomosis is present, the connecting vessel can be transverse to or form an
      oblique angle with the umbilical arteries. We observed a striking increase in the
      number of artery pairs connected by a transverse vessel in specimens from
      hypertensive subjects relative to those from normotensive subjects. Moreover,
      placentas from hypertensive donors were small if the umbilical arteries were
      connected by an oblique anastomosis. In addition, the length of the anastomosis
      and its distance from the cord insertion was shorter in specimens from
      hypertensive compared to normotensive subjects. We conclude that pregnancy
      induced hypertension alters the anatomy of Hyrtl's anastomosis, and in some
      circumstances, the placenta.

PMID- 24591341
TI  - Update: ambulatory blood pressure monitoring in children and adolescents: a
      scientific statement from the American Heart Association.

PMID- 24591345
TI  - CO2 capture and conversion with a multifunctional polyethyleneimine-tethered
      iminophosphine iridium catalyst/adsorbent.
AB  - Tunable, multifunctional materials able to capture CO2 and subsequently catalyze
      its conversion to formic acid were synthesized by the modification of branched
      polyethyleneimine (PEI) with an iminophosphine ligand coordinated to an Ir
      precatalyst. The molecular weight of the PEI backbone was an important component
      for material stability and catalytic activity, which were inversely related. The
      amine functionalities on PEI served three roles: 1) primary amines were used to
      tether the ligand and precatalyst, 2) amines were used to capture CO2 , and 3)
      amines served as a base for formate stabilization during catalysis. Ligand
      studies on imine and phosphine based ligands showed that a bidentate
      iminophosphine ligand resulted in the highest catalytic activity. X-ray
      photoelectron spectroscopy revealed that an increase in Ir 4f binding energy led
      to an increase in catalytic activity, which suggests that the electronics of the
      metal center play a significant role in catalysis. Catalyst loading studies
      revealed that there is a critical balance between free amines and ligand-metal
      sites that must be reached to optimize catalytic activity. Thus, it was found
      that the CO2 capture and conversion abilities of these materials could be
      optimized for reaction conditions by tuning the structure of the PEI-tethered
      materials.

PMID- 24591346
TI  - The future of stress and health research.

PMID- 24591351
TI  - Development and screening of a series of antibody-conjugated and silica-coated
      iron oxide nanoparticles for targeting the prostate-specific membrane antigen.
AB  - The prostate-specific membrane antigen (PSMA) is an established target for the
      delivery of cancer therapeutic and imaging agents due to its high expression on
      the surface of prostate cancer cells and within the neovasculature of other solid
      tumors. Here, we describe the synthesis and screening of antibody-conjugated
      silica-coated iron oxide nanoparticles for PSMA-specific cell targeting. The
      humanized anti-PSMA antibody, HuJ591, was conjugated to a series of nanoparticles
      with varying densities of polyethylene glycol and primary amine groups.
      Customized assays utilizing iron spectral absorbance and enzyme-linked
      immunoassay (ELISA) were developed to screen microgram quantities of nanoparticle
      formulations for immunoreactivity and cell targeting ability. Antibody and PSMA
      specific targeting of the optimized nanoparticle was evaluated using an isogenic
      PSMA-positive and PSMA-negative cell line pair. Specific nanoparticle targeting
      was confirmed by iron quantification with inductively coupled plasma mass
      spectrometry (ICP-MS). These methods and nanoparticles support the promise of
      targeted theranostic agents for future treatment of prostate and other cancers. 

PMID- 24591352
TI  - Long noncoding RNA HOTAIR is relevant to cellular proliferation, invasiveness,
      and clinical relapse in small-cell lung cancer.
AB  - Small-cell lung cancer (SCLC) is a subtype of lung cancer with poor prognosis. To
      identify accurate predictive biomarkers and effective therapeutic modalities, we
      focus on a long noncoding RNA, Hox transcript antisense intergenic RNA (HOTAIR),
      and investigated its expression, cellular functions, and clinical relevance in
      SCLC. In this study, HOTAIR expression was assessed in 35 surgical SCLC samples
      and 10 SCLC cell lines. The efficacy of knockdown of HOTAIR by siRNA transfection
      was evaluated in SBC-3 cells in vitro, and the gene expression was analyzed using
      microarray. HOTAIR was expressed highly in pure, rather than combined, SCLC (P =
      0.012), that the subgroup with high expression had significantly more pure SCLC
      (P = 0.04), more lymphatic invasion (P = 0.03) and more relapse (P = 0.04) than
      the low-expression subgroup. The knockdown of HOTAIR in SBC-3 cells led to
      decreased proliferation activity and decreased invasiveness in vitro. Gene
      expression analysis indicated that depletion of HOTAIR resulted in upregulation
      of cell adhesion-related genes such as ASTN1, PCDHA1, and mucin production
      related genes such as MUC5AC, and downregulation of genes involved in neuronal
      growth and signal transduction including NTM and PTK2B. Our results suggest that
      HOTAIR has an oncogenic role in SCLC and could be a prognostic biomarker and
      therapeutic target.

PMID- 24591360
TI  - Surgical operating environment procedures should be standardised to improve
      safety, taskforce recommends.

PMID- 24591358
TI  - Exploring the feasibility of using electronic health records in the surveillance
      of fetal alcohol syndrome.
AB  - BACKGROUND: Explore the use of electronic health records (EHRs) in fetal alcohol
      syndrome (FAS) surveillance systems. METHODS: Using EHRs we identified diagnoses
      and anthropometric measurements related to the FAS criteria developed by the
      Fetal Alcohol Syndrome Surveillance Network (FASSNet) among children aged 0 to 12
      years. RESULTS: There were 143,393 distinct children aged between 0 and 12 years
      enrolled in Kaiser Permanente, Georgia, during the study period. Based on
      diagnoses and anthropometric measurements, 20,101 children met at least one
      criterion of interest, and when grouped into combinations of different criteria
      there were 2285 who met GROWTH+CNS criteria, 76 children who met GROWTH+FACE
      criteria, 107 children who met CNS+FACE criteria, and 93 children who met
      GROWTH+CNS+FACE criteria. The prevalence of FAS as defined by FASSNet is 1.92 per
      1000 children. We linked 17,084 (85.0%) children to their mothers in the health
      plan; only 3% of mothers of children in the GROWTH+CNS+FACE group had an
      indication of alcohol or drugs use, but they had the highest rate of depression
      (39%). CONCLUSION: Data of utility in identification of FAS are readily available
      in EHRs and may serve as a basis for intervention with at-risk children and in
      planning of future FAS surveillance programs.

PMID- 24591361
TI  - Bis(dipyridophenazine)(2-(2'-pyridyl)pyrimidine-4-carboxylic acid)ruthenium(II)
      hexafluorophosphate: a lesson in stubbornness.
AB  - Ruthenium complexes are currently considered to be among the most promising
      alternatives to platinum anticancer drugs. In this work, thirteen structural
      analogues and organelle/receptor-targeting peptide bioconjugates of a cytotoxic
      bis(dppz)-Ru(II) complex [Ru(dppz)2 (CppH)](PF6 )2 (1) were prepared,
      characterized, and assessed for their cytotoxicity and cellular localization
      (CppH=2-(2'-pyridyl)pyrimidine-4-carboxylic acid; dppz=dipyrido[3,2-a:2',3'
      c]phenazine). It was observed that structural modifications (lipophilicity,
      charge, and size-based) result in the cytotoxic potency of 1 being compromised.
      Confocal microscopy studies revealed that unlike 1, the screened
      complexes/bioconjugates do not have a preferential accumulation in mitochondria.
      The results of this important structure-activity relationship strongly support
      our initial hypothesis that accumulation in mitochondria is crucial for 1 to
      exert its cytotoxic action. 

PMID- 24591362
TI  - Small molecular donors for organic solar cells obtained by simple and clean
      synthesis.
AB  - A small donor-acceptor molecule is synthesized in a two-step procedure involving
      reaction of N,N-diphenylhydrazine on 2,5-diformylthiophene and Knoevenagel
      condensation. Results of UV/Vis absorption spectroscopy and cyclic voltammetry
      show that replacement of the phenyl ring bridge of a reference compound 2 by an
      azo group produces a slight red-shift of lambdamax, an enhancement of the
      molecular absorption coefficient, and a decrease of the energy level of the
      frontier orbitals. A preliminary evaluation of the potentialities of compound 1
      as donor material in a basic bilayer planar heterojunction cell of 28 mm(2)
      active area using C60 as acceptor gave a short-circuit current density of 6.32 mA
      cm(-2) and a power conversion efficiency of 2.07 %.

PMID- 24591363
TI  - Xenograft tolerance and immune function of human T cells developing in pig thymus
      xenografts.
AB  - Transplantation of xenogeneic thymus tissue allows xenograft tolerance induction
      in the highly disparate pig-to-mouse model. Fetal swine thymus (SW THY) can
      support the generation of a diverse human T cell repertoire that is tolerant of
      the pig in vitro. We demonstrate that SW THY generates all human T cell subsets,
      including regulatory T cells (Tregs), in similar numbers as fetal human thymus
      (HU THY) grafts in immunodeficient mice receiving the same human CD34(+) cells.
      Peripheral T cells are specifically tolerant to the mouse and to the human and
      porcine donors, with robust responses to nondonor human and pig Ags. Specific
      tolerance is observed to pig skin grafts sharing the THY donor MHC. SW THY
      generated peripheral Tregs show similar function, but include lower percentages
      of naive-type Tregs compared with HU THY-generated Tregs. Tregs contribute to
      donor-pig specific tolerance. Peripheral human T cells generated in SW THY
      exhibit reduced proportions of CD8(+) T cells and reduced lymphopenia-driven
      proliferation and memory-type conversion, accelerated decay of memory-type cells,
      and reduced responses to protein Ags. Thus, SW thymus transplantation is a
      powerful xenotolerance approach for human T cells. However, immune function may
      be further enhanced by strategies to permit positive selection by autologous HLA
      molecules. 

PMID- 24591366
TI  - alphaPIX RhoGEF supports positive selection by restraining migration and
      promoting arrest of thymocytes.
AB  - Thymocytes mature in a series of stages by migrating through specific areas of
      the thymus and interacting with other cells to receive the necessary
      developmental signals; however, little is known about the molecular mechanisms
      governing this migration. We report that murine thymocytes with a knockout
      mutation in alpha-PAK (p21-activated kinase)-interacting exchange factor (PIX;
      Arhgef6), an activator of Rho GTPases, showed greatly increased motility and
      altered morphology in two-dimensional migration on ICAM-1. alphaPIX was also
      required for efficient positive selection, but not negative selection, of
      thymocytes. TCR signaling was normal in alphaPix(-) thymocytes, indicating that
      the effects of alphaPIX on positive selection are largely independent of TCR
      signaling. alphaPix(-) thymocytes also paused less during migration in the thymic
      cortex, interacted less with ICAM-1 coated beads, and could overcome TCR stop
      signals, consistent with defective scanning behavior. These results identify
      alphaPIX as a regulator of thymocyte migration and subsequent arrest that is
      linked to positive selection. 

PMID- 24591364
TI  - Central role of conventional dendritic cells in regulation of bone marrow release
      and survival of neutrophils.
AB  - Neutrophils are the most abundant cell type in the immune system and play an
      important role in the innate immune response. Using a diverse range of mouse
      models with either defective dendritic cell (DC) development or conditional DC
      depletion, we provide in vivo evidence indicating that conventional DCs play an
      important role in the regulation of neutrophil homeostasis. Flk2, Flt3L, and
      Batf3 knockout mice, which have defects in DC development, have increased numbers
      of liver neutrophils in the steady state. Conversely, neutrophil frequency is
      reduced in DC-specific PTEN knockout mice, which have an expansion of CD8(+) and
      CD103(+) DCs. In chimeric CD11c-DTR mice, conventional DC depletion results in a
      systemic increase of neutrophils in peripheral organs in the absence of
      histological inflammation or an increase in proinflammatory cytokines. This
      effect is also present in splenectomized chimeric CD11c-DTR mice and is absent in
      chimeric mice with 50% normal bone marrow. In chimeric CD11c-DTR mice, diphtheria
      toxin treatment results in enhanced neutrophil trafficking from the bone marrow
      into circulation and increased neutrophil recruitment. Moreover, there is an
      increased expression of chemokines/cytokines involved in neutrophil homeostasis
      and reduced neutrophil apoptosis. These data underscore the role of the DC pool
      in regulating the neutrophil compartment in nonlymphoid organs. 

PMID- 24591365
TI  - Enhanced antibody responses to an HIV-1 membrane-proximal external region antigen
      in mice reconstituted with cultured lymphocytes.
AB  - We have shown that the protective HIV-1 Ab, 2F5, avidly reacts with a conserved
      mammalian self-Ag, kynureninase, and that the development of B cells specific for
      the 2F5 epitope is constrained by immunological tolerance. These observations
      suggest that the capacity to mount Ab responses to the 2F5 epitope is mitigated
      by tolerance, but such capacity may be latent in the pretolerance and/or anergic
      B cell pools. In this study, we use B cell tetramer reagents to track the
      frequencies of B cells that recognize the HIV-1 2F5 epitope (SP62): in C57BL/6
      mice, SP62-binding transitional B cells are readily identified in bone marrow but
      are lost during subsequent development. Unsurprisingly then, immunization with
      SP62 immunogen does not elicit significant humoral responses in normal C57BL/6
      mice. Reconstitution of Rag1(null) mice with normal congenic B cells that have
      matured in vitro restores the capacity to mount significant serum Ab and germinal
      center responses to this HIV-1 epitope. These B cell cultures are permissive for
      the development of autoreactive B cells and support the development of SP62
      specific B cell compartments normally lost in 2F5 Ab knockin mice. The recovery
      of humoral responses to the 2F5/SP62 epitope of HIV-1 by reconstitution with B
      cells containing forbidden, autoreactive clones provides direct evidence that
      normal C57BL/6 mice latently possess the capacity to generate humoral responses
      to a conserved, neutralizing HIV-1 epitope. 

PMID- 24591367
TI  - Cutting edge: control of Mycobacterium tuberculosis infection by a subset of lung
      parenchyma-homing CD4 T cells.
AB  - Th1 cells are critical for containment of Mycobacterium tuberculosis infection,
      but little else is known about the properties of protective CD4 T cell responses.
      In this study, we show that the pulmonary Th1 response against M. tuberculosis is
      composed of two populations that are either CXCR3(hi) and localize to lung
      parenchyma or are CX3CR1(hi)KLRG1(hi) and are retained within lung blood
      vasculature. M. tuberculosis-specific parenchymal CD4 T cells migrate rapidly
      back into the lung parenchyma upon adoptive transfer, whereas the intravascular
      effectors produce the highest levels of IFN-gamma in vivo. Importantly,
      parenchymal T cells displayed greater control of infection compared with the
      intravascular counterparts upon transfer into susceptible T cell-deficient hosts.
      Thus, we identified a subset of naturally generated M. tuberculosis-specific CD4
      T cells with enhanced protective capacity and showed that control of M.
      tuberculosis correlates with the ability of CD4 T cells to efficiently enter the
      lung parenchyma rather than produce high levels of IFN-gamma. 

PMID- 24591368
TI  - Cutting edge: committed Th1 CD4+ T cell differentiation blocks pregnancy-induced
      Foxp3 expression with antigen-specific fetal loss.
AB  - Pregnancy stimulates induced Foxp3 expression among maternal CD4(+) T cells with
      fetal specificity. Although sustained maternal regulatory CD4(+) T cell (Treg)
      expansion is essential for maintaining fetal tolerance during pregnancy, the
      necessity for Foxp3(+) cells with fetal specificity remains undefined. In this
      study, we demonstrate that mitigating Treg differentiation among maternal CD4(+)
      T cells with a single surrogate fetal specificity elicits Ag-specific fetal loss.
      Using recombinant Listeria monocytogenes to prime stably differentiated Th1
      CD4(+) T cells with fetal I-A(b):2W1S55-68 specificity refractory to pregnancy
      induced Foxp3 expression, we show that Ag delivery by cytoplasmic L.
      monocytogenes causes selective loss of 2W1S(+) offspring through CD4 cell- and
      IFN-gamma-dependent pathways. In contrast, CD4(+) T cells primed by L.
      monocytogenes restricted from the cell cytoplasm are markedly more plastic for
      induced Foxp3 expression, with normal pregnancy outcomes. Thus, committed Th1
      polarization blocks pregnancy induced Treg differentiation among maternal CD4(+)
      T cells with fetal specificity and triggers Ag-specific fetal loss. 

PMID- 24591369
TI  - Aspergillus and Fusarium corneal infections are regulated by Th17 cells and IL-17
      producing neutrophils.
AB  - Fusarium and Aspergillus species of mold are major causes of corneal infections
      in the United States and worldwide, resulting in severe visual impairment and
      blindness. As there is evidence for T cell responses to these pathogenic fungi in
      infected individuals, we examined the role of IL-17A (IL-17) and IFN-gamma in
      murine models of fungal keratitis. We found that C57BL/6 mice given intratracheal
      or s.c. immunization of conidia prior to corneal infection exhibited enhanced
      fungal killing and lower corneal opacity compared with unimmunized mice.
      Protective immunity was associated with temporal recruitment of IL-17-producing
      neutrophils and Th17 and Th1 cells and dependent on production of IL-17 but not
      IFN-gamma. Protection was also impaired in neutrophil-depleted and Rag2(-/-)
      mice. Together, the results of these studies identify an essential role for IL-17
      producing neutrophils and Th17 cells in regulating the growth of fungal hyphae
      and the severity of corneal disease. 

PMID- 24591370
TI  - Transcription factor IRF4 regulates germinal center cell formation through a B
      cell-intrinsic mechanism.
AB  - In response to antigenic stimulation, mature B cells interact with follicular
      helper T cells in specialized structures called germinal centers (GCs), which
      leads to the development of memory B cells and Ab-secreting plasma cells. The
      transcription factor IFN regulatory factor 4 (IRF4) is essential for the
      formation of follicular helper T cells and thus GCs, although whether IRF4 plays
      a distinct role in GC B cells remains contentious. RNAseq analysis on ex vivo
      derived mouse B cell populations showed that Irf4 was lowly expressed in naive B
      cells, highly expressed in plasma cells, but absent from GC B cells. In this
      study, we used conditional deletion of Irf4 in mature B cells as well as wild
      type and Irf4-deficient mixed bone marrow chimeric mice to investigate how and
      where IRF4 plays its essential role in GC formation. Strikingly, GC formation was
      severely impaired in mice in which Irf4 was conditionally deleted in mature B
      cells, after immunization with protein Ags or infection with Leishmania major.
      This effect was evident as early as day 5 following immunization, before the
      development of GCs, indicating that Irf4 was required for the development of
      early GC B cells. This defect was B cell intrinsic because Irf4-deficient B cells
      in chimeric mice failed to participate in the GC in response to L. major or
      influenza virus infection. Taken together, these data demonstrate a B cell
      intrinsic requirement for IRF4 for not only the development of Ab secreting
      plasma cells but also for GC formation. 

PMID- 24591372
TI  - The degree of CD4+ T cell autoreactivity determines cellular pathways underlying
      inflammatory arthritis.
AB  - Although therapies targeting distinct cellular pathways (e.g., anticytokine
      versus anti-B cell therapy) have been found to be an effective strategy for at
      least some patients with inflammatory arthritis, the mechanisms that determine
      which pathways promote arthritis development are poorly understood. We have used
      a transgenic mouse model to examine how variations in the CD4(+) T cell response
      to a surrogate self-peptide can affect the cellular pathways that are required
      for arthritis development. CD4(+) T cells that are highly reactive with the self
      peptide induce inflammatory arthritis that affects male and female mice equally.
      Arthritis develops by a B cell-independent mechanism, although it can be
      suppressed by an anti-TNF treatment, which prevented the accumulation of effector
      CD4(+) Th17 cells in the joints of treated mice. By contrast, arthritis develops
      with a significant female bias in the context of a more weakly autoreactive
      CD4(+) T cell response, and B cells play a prominent role in disease
      pathogenesis. In this setting of lower CD4(+) T cell autoreactivity, B cells
      promote the formation of autoreactive CD4(+) effector T cells (including Th17
      cells), and IL-17 is required for arthritis development. These studies show that
      the degree of CD4(+) T cell reactivity for a self-peptide can play a prominent
      role in determining whether distinct cellular pathways can be targeted to prevent
      the development of inflammatory arthritis. 

PMID- 24591374
TI  - The epidermal growth factor receptor is a regulator of epidermal complement
      component expression and complement activation.
AB  - The complement system is activated in response to tissue injury. During wound
      healing, complement activation seems beneficial in acute wounds but may be
      detrimental in chronic wounds. We found that the epidermal expression of many
      complement components was only increased to a minor extent in skin wounds in vivo
      and in cultured keratinocytes after exposure to supernatant from stimulated
      mononuclear cells. In contrast, the epidermal expression of complement components
      was downregulated in ex vivo injured skin lacking the stimulation from
      infiltrating inflammatory cells but with intact injury-induced epidermal growth
      factor receptor (EGFR)-mediated growth factor response. In cultured primary
      keratinocytes, stimulation with the potent EGFR ligand, TGF-alpha, yielded a
      significant downregulation of complement component expression. Indeed, EGFR
      inhibition significantly enhanced the induction of complement components in
      keratinocytes and epidermis following stimulation with proinflammatory cytokines.
      Importantly, EGFR inhibition of cultured keratinocytes either alone or in
      combination with proinflammatory stimulus promoted activation of the complement
      system after incubation with serum. In keratinocytes treated solely with the EGFR
      inhibitor, complement activation was dependent on serum-derived C1q, whereas in
      keratinocytes stimulated with a combination of proinflammatory cytokines and EGFR
      inhibition, complement activation was found even with C1q-depleted serum. In
      contrast to human keratinocytes, EGFR inhibition did not enhance complement
      component expression or cause complement activation in murine keratinocytes.
      These data demonstrate an important role for EGFR in regulating the expression of
      complement components and complement activation in human epidermis and
      keratinocytes and, to our knowledge, identify for the first time a pathway
      important for the epidermal regulation of complement activation. 

PMID- 24591373
TI  - NOD2 regulates CXCR3-dependent CD8+ T cell accumulation in intestinal tissues
      with acute injury.
AB  - Polymorphisms in NOD2 confer risk for Crohn's disease, characterized by
      intestinal inflammation. How NOD2 regulates both inflammatory and regulatory
      intestinal T cells, which are critical to intestinal immune homeostasis, is not
      well understood. Anti-CD3 mAb administration is used as therapy in human
      autoimmune diseases, as well as a model of transient intestinal injury. The
      stages of T cell activation, intestinal injury, and subsequent T tolerance are
      dependent on migration of T cells into the small intestinal (SI) lamina propria.
      Upon anti-CD3 mAb treatment of mice, we found that NOD2 was required for optimal
      small intestinal IL-10 production, in particular from CD8(+) T cells. This
      requirement was associated with a critical role for NOD2 in SI CD8(+) T cell
      accumulation and induction of the CXCR3 ligands CXCL9 and CXCL10, which regulate
      T cell migration. NOD2 was required in both the hematopoietic and
      nonhematopoietic compartments for optimal expression of CXCR3 ligands in
      intestinal tissues. NOD2 synergized with IFN-gamma to induce CXCL9 and CXCL10
      secretion in dendritic cells, macrophages, and intestinal stromal cells in vitro.
      Consistent with the in vitro studies, during anti-CD3 mAb treatment in vivo,
      CXCR3 blockade, CD8(+) T cell depletion, or IFN-gamma neutralization each
      inhibited SI CD8(+) T cell recruitment, and reduced chemokine expression and IL
      10 expression. Thus, NOD2 synergizes with IFN-gamma to promote CXCL9 and CXCL10
      expression, thereby amplifying CXCR3-dependent SI CD8(+) T cell migration during
      T cell activation, which, in turn, contributes to induction of both inflammatory
      and regulatory T cell outcomes in the intestinal environment. 

PMID- 24591371
TI  - Relapsing-remitting central nervous system autoimmunity mediated by GFAP-specific
      CD8 T cells.
AB  - Multiple sclerosis (MS) is an inflammatory disease of the CNS that causes the
      demyelination of nerve cells and destroys oligodendrocytes, neurons, and axons.
      Historically, MS has been thought to be a CD4 T cell-mediated autoimmune disease
      of CNS white matter. However, recent studies identified CD8 T cell infiltrates
      and gray matter lesions in MS patients. These findings suggest that CD8 T cells
      and CNS Ags other than myelin proteins may be involved during the MS disease
      process. In this article, we show that CD8 T cells reactive to glial fibrillary
      acidic protein (GFAP), a protein expressed in astrocytes, can avoid tolerance
      mechanisms and, depending upon the T cell-triggering event, drive unique aspects
      of inflammatory CNS autoimmunity. In GFAP-specific CD8 TCR-transgenic (BG1) mice,
      tissue resident memory-like CD8 T cells spontaneously infiltrate the gray matter
      and white matter of the CNS, resulting in a relapsing-remitting CNS autoimmunity.
      The frequency, severity, and remissions from spontaneous disease are controlled
      by the presence of polyclonal B cells. In contrast, a viral trigger induces GFAP
      specific CD8 T effector cells to exclusively target the meninges and
      vascular/perivascular space of the gray and white matter of the brain, causing a
      rapid, acute CNS disease. These findings demonstrate that the type of CD8 T cell
      triggering event can determine the presentation of distinct CNS autoimmune
      disease pathologies. 

PMID- 24591375
TI  - Oxypurinol directly and immediately activates the drug-specific T cells via the
      preferential use of HLA-B*58:01.
AB  - Allopurinol (ALP) hypersensitivity is a major cause of severe cutaneous adverse
      reactions and is strongly associated with the HLA-B*58:01 allele. However, it can
      occur in the absence of this allele with identical clinical manifestations. The
      immune mechanism of ALP-induced severe cutaneous adverse reactions is poorly
      understood, and the T cell-reactivity pattern in patients with or without the HLA
      B*58:01 allele is not known. To understand the interactions among the drug, HLA,
      and TCR, we generated T cell lines that react to ALP or its metabolite oxypurinol
      (OXP) from HLA-B*58:01(+) and HLA-B*58:01(-) donors and assessed their
      reactivity. ALP/OXP-specific T cells reacted immediately to the addition of the
      drugs and bypassed intracellular Ag processing, which is consistent with the
      "pharmacological interaction with immune receptors" (p-i) concept. This direct
      activation occurred regardless of HLA-B*58:01 status. Although most OXP-specific
      T cells from HLA-B*58:01(+) donors were restricted by the HLA-B*58:01 molecule
      for drug recognition, ALP-specific T cells also were restricted to other MHC
      class I molecules. This can be explained by in silico docking data that suggest
      that OXP binds to the peptide-binding groove of HLA-B*58:01 with higher affinity.
      The ensuing T cell responses elicited by ALP or OXP were not limited to
      particular TCR Vbeta repertoires. We conclude that the drug-specific T cells are
      activated by OXP bound to HLA-B*58:01 through the p-i mechanism. 

PMID- 24591376
TI  - Protective immunity and defects in the neonatal and elderly immune response to
      sepsis.
AB  - Populations encompassing extremes of age, including neonates and elderly, have
      greater mortality from sepsis. We propose that the increased mortality observed
      in the neonatal and elderly populations after sepsis is due to fundamental
      differences in host-protective immunity and is manifested at the level of the
      leukocyte transcriptome. Neonatal (5-7 d), young adult (6-12 wk), or elderly (20
      24 mo) mice underwent a cecal slurry model of intra-abdominal sepsis. Both
      neonatal and elderly mice exhibited significantly greater mortality to sepsis (p
      < 0.05). Neonates in particular exhibited significant attenuation of their
      inflammatory response (p < 0.05), as well as reductions in cell recruitment and
      reactive oxygen species production (both p < 0.05), all of which could be
      confirmed at the level of the leukocyte transcriptome. In contrast, elderly mice
      were also more susceptible to abdominal peritonitis, but this was associated with
      no significant differences in the magnitude of the inflammatory response, reduced
      bacterial killing (p < 0.05), reduced early myeloid cell activation (p < 0.05),
      and a persistent inflammatory response that failed to resolve. Interestingly,
      elderly mice expressed a persistent inflammatory and immunosuppressive response
      at the level of the leukocyte transcriptome, with failure to return to baseline
      by 3 d. This study reveals that neonatal and elderly mice have profoundly
      different responses to sepsis that are manifested at the level of their
      circulating leukocyte transcriptome, although the net result of increased
      mortality is similar. Considering these differences are fundamental aspects of
      the genomic response to sepsis, interventional therapies will require
      individualization based on the age of the population. 

PMID- 24591377
TI  - IkappaBepsilon is a key regulator of B cell expansion by providing negative
      feedback on cRel and RelA in a stimulus-specific manner.
AB  - The transcription factor NF-kappaB is a regulator of inflammatory and adaptive
      immune responses, yet only IkappaBalpha was shown to limit NF-kappaB activation
      and inflammatory responses. We investigated another negative feedback regulator,
      IkappaBepsilon, in the regulation of B cell proliferation and survival. Loss of
      IkappaBepsilon resulted in increased B cell proliferation and survival in
      response to both antigenic and innate stimulation. NF-kappaB activity was
      elevated during late-phase activation, but the dimer composition was stimulus
      specific. In response to IgM, cRel dimers were elevated in IkappaBepsilon
      deficient cells, yet in response to LPS, RelA dimers also were elevated. The
      corresponding dimer-specific sequences were found in the promoters of
      hyperactivated genes. Using a mathematical model of the NF-kappaB-signaling
      system in B cells, we demonstrated that kinetic considerations of IkappaB kinase
      signaling input and IkappaBepsilon's interactions with RelA- and cRel-specific
      dimers could account for this stimulus specificity. cRel is known to be the key
      regulator of B cell expansion. We found that the RelA-specific phenotype in LPS
      stimulated cells was physiologically relevant: unbiased transcriptome profiling
      revealed that the inflammatory cytokine IL-6 was hyperactivated in
      IkappaBepsilon(-/-) B cells. When IL-6R was blocked, LPS-responsive
      IkappaBepsilon(-/-) B cell proliferation was reduced to near wild-type levels.
      Our results provide novel evidence for a critical role for immune-response
      functions of IkappaBepsilon in B cells; it regulates proliferative capacity via
      at least two mechanisms involving cRel- and RelA-containing NF-kappaB dimers.
      This study illustrates the importance of kinetic considerations in understanding
      the functional specificity of negative-feedback regulators. 

PMID- 24591378
TI  - In silico analysis of AHJD-like viruses, Staphylococcus aureus phages S24-1 and
      S13', and study of phage S24-1 adsorption.
AB  - Staphylococcus aureus is a clinically important bacterium that is commensal in
      both humans and animals. Bacteriophage (phage) attachment to the host bacterial
      surface is an important process during phage infection, which involves
      interactions between phage receptor-binding proteins and host receptor molecules.
      However, little information is available on the receptor-binding protein of S.
      aureus phages. S. aureus virulent phages S24-1 and S13' (family Podoviridae,
      genus AHJD-like viruses) were isolated from sewage. In the present study, we
      investigated the receptor-binding protein of AHJD-like viruses using phage S24-1.
      First, based on a comparative genomic analysis of phages S24-1 and S13', open
      reading frame 16 (ORF16) of phage S24-1 was speculated to be the receptor-binding
      protein, which possibly determines the host range. Second, we demonstrated that
      this was the receptor-binding protein of phage S24-1. Third, our study suggested
      that wall teichoic acids in the cell walls of S. aureus are the main receptor
      molecules for ORF16 and phage S24-1. Finally, the C-terminal region of ORF16 may
      be essential for binding to S. aureus. These results strongly suggest that ORF16
      of phage S24-1 and its homologs may be the receptor-binding proteins of AHJD-like
      viruses. 

PMID- 24591379
TI  - Iatrogenic oesophageal transection during laparoscopic sleeve gastrectomy.
AB  - Laparoscopic sleeve gastrectomy has been hailed as an easy and safe procedure
      when compared with other bariatric operations. However, it may be associated with
      well-recognised early complications such as leaks and bleeding, as well as late
      ones such as stenosis and weight regain. Iatrogenic complete oesophageal
      transection has never been reported before as a complication. We report a case of
      complete oesophageal transection during laparoscopic sleeve gastrectomy that was
      not recognised intraoperatively. The repair of this iatrogenic injury was staged,
      with the final stage carried out some 3 months after the initial procedure. This
      case report highlights the possible occurrence of complete oesophageal
      transection during laparoscopic sleeve gastrectomy, and suggests steps to avoid
      and correct such complications. 

PMID- 24591380
TI  - Abdominal wall necrotising fasciitis due to dislodged percutaneous endoscopic
      gastrostomy tube.
AB  - Accessing the stomach via a percutaneous endoscopic gastrostomy (PEG) tube is the
      preferred (and sometimes the only) method for providing enteral nutritional
      support in disabled patients. However, it is associated with serious and
      potentially lethal complications which must be completely recognised by
      physicians, by nurses and especially by radiologists. Abdominal wall necrotising
      fasciitis of a dislodged or leaking PEG tube could be a lethal complication. We
      present a case of a 74-year-old bed bound woman who was admitted to our hospital
      with fever and abdominal pain. On presentation, the patient's temperature was 36
      degrees C and laboratory tests showed leucocytosis. Physical examination revealed
      extensive redness of the abdominal wall, diffuse tenderness of the abdomen and
      yellowish discharge around the gastrostomy. 

PMID- 24591381
TI  - Spotty skin pigmentation and multiple blue naevi as cutaneous markers for spinal
      melanotic schwannoma.
AB  - Spinal melanotic schwannomas are rare spinal tumours with a very poor prognosis
      in terms of mortality due to difficulty in complete resection and local
      recurrences. A 67-year-old man presented with acute onset progressive paraparesis
      for 2 weeks. The patient also had spotty skin pigmentations (blue naevi) in his
      right lateral thigh. MRI revealed an intradural extramedullary enhancing lesion
      in the lower thoracic cord level. With a preoperative diagnosis of simple nerve
      sheath tumour excision was planned. At laminotomy, an infiltrating "en plaque"
      like lesion reaching up to mid and upper thoracic cord level was identified and
      excision was carried out. Postoperative histopathology was unique with the
      identification of melanin and presence of epitheloid cells, with the additional
      detection of psammoma bodies and adipose-like cells. Melanotic schwannomas though
      rare and carry poor prognosis must be borne in mind in patients with spotty skin
      pigmentation and acute onset limb weakness. 

PMID- 24591382
TI  - Ischaemic stroke as initial presentation of systemic malignancy.
AB  - Ischaemic stroke as the initial presentation of systemic malignancy is reported
      infrequently and is characterised by ischaemic lesions that exceed the vascular
      territory of a single vessel. There is also a high rate of early stroke
      recurrence. Several pathophysiological mechanisms are known to cause
      cerebrovascular complications in malignancies, as a direct effect of the tumour,
      paraneoplastic or even of the tumour treatment itself. Prognosis is reportedly
      poor, treatment is symptomatic and at best anecdotal. We present a case report
      and available literature. 

PMID- 24591383
TI  - Dual pathology of the submandibular gland: plasmacytoma and pleomorphic adenoma.
AB  - Synchronous tumours of different histological types involving the salivary gland
      are very rare. There have been cases reported in the literature of such tumours
      occurring in the parotid gland. A 52-year-old man presented with a 4-year history
      of gradually increasing painless swelling in the right submandibular region. The
      ultrasound scan of the neck showed features suggestive of a submandibular
      sialadenitis. The right submandibular gland was then surgically excised and sent
      for histopathological examination. The features showed a unique dual pathology of
      the submandibular gland, that is, a plasmacytoma and a pleomorphic adenoma. Such
      a synchronous double pathology involving the submandibular gland has not been
      reported in the literature. A review of the literature suggests a good prognosis
      for the extramedullary plasmacytoma, provided multiple myeloma is ruled out. In
      18 months of follow-up, the patient has been asymptomatic with a negative myeloma
      workup. 

PMID- 24591385
TI  - Novel therapeutic use of Versajet for intestinal mucormycosis.
AB  - We describe the case of a 17-year-old boy who developed intestinal mucormycosis
      from Rhizophus oryzae (order Mucorales) following chemotherapy for the management
      of acute myeloid leukaemia. He underwent a hemicolectomy and further surgery
      utilising the pressure washing of Versajet to debride colonised fungal
      collections from the psoas muscle limiting the amount of surgical debridement
      needed. 

PMID- 24591384
TI  - Triple communicating complicated hepatic hydatid cyst: an unusual presentation
      and laparoendoscopic management.
AB  - Echinococcal disease in humans had been widely reported in the literature for its
      unusual presentation and location. We discuss a rare case of suppurated left
      hepatic hydatid cyst with contaminant transdiaphragmatic rupture communicating
      into the right pleural cavity along with fistulisation of cyst into the left
      hepatic duct and stomach which is very rare according to our knowledge. A 65-year
      old man presented to us with features of cholangitis and sepsis. Initial
      radiological investigations revealed multiloculated cystic mass in the left lobe
      of cirrhotic liver communicating with the left hepatic duct and extending to the
      right pleural cavity with dilated common bile duct. Endoscopic retrograde
      cholangiopancreatography confirmed the diagnosis yielding hydatid membranes with
      presence of transgastric fistula in the left hepatic duct and provided
      postoperatively continuous internal drainage. Old age, complicated cyst,
      compromised respiratory status, sepsis and cirrhotic liver precluded us to plan
      for conservative surgical approach (laparoscopic drainage of mediastinal
      contents) with successful outcome. 

PMID- 24591386
TI  - Takes two to tango.
AB  - A 17-year-old girl was admitted with acute abdominal pain, vomiting and a
      leucocytosis, and was initially thought to have appendicitis. She underwent
      laparoscopic appendicectomy, where the tip of the appendix was noted to be mildly
      inflamed and she was discharged home the day after surgery. Two days later, she
      re-presented with small bowel obstruction which was subsequently demonstrated to
      be due to ingestion of five magnetic beads. She required a laparotomy and small
      bowel resection to resolve the obstruction, but has since fully recovered. This
      case highlights the potential intestinal complications caused by the intake of
      magnetic objects, and based on a literature review a number of recommendations
      are made to guide clinicians when managing similar cases. 

PMID- 24591387
TI  - Opsoclonus myoclonus syndrome due to squamous cell carcinoma of the oesophagus.
AB  - We present the case of a 47-year-old woman with encephalopathy, ataxia and
      oscillopsia diagnosed with opsoclonus myoclonus syndrome (OMS). In adults, OMS in
      the context of encephalopathy is commonly paraneoplastic. A CT of the chest,
      abdomen and pelvis and a gastroscopy were performed and were normal. A
      fluorodeoxyglucose positron emission tomography CT scan demonstrated increased
      uptake in the mid-oesophagus and an endoscopic ultrasound examination
      demonstrated intramural thickening of 5 mm with no epithelial lesion. The patient
      was treated with three courses of intravenous immunoglobulin (IvIg) with
      improvement in her symptoms. A year following the initial presentation a repeat
      endoscopic examination demonstrated an ulcerated oesophageal carcinoma with
      regional lymph node involvement. The patient was treated with neo adjuvant
      chemotherapy prior to oesophagectomy. The patient's symptoms resolved within 6
      months of tumour resection without the need for further IvIg. Unfortunately,
      after a further 6 months the patient developed liver metastases and died. 

PMID- 24591388
TI  - Familial bulbar urethral strictures.
AB  - Strictures are commonly encountered in the urological practice. The most common
      aetiologies are infection, trauma and iatrogenic events. Familial occurrence of
      urethral stricture is exceptionally rare. We present a case in which bulbar
      urethral strictures developed in a father and his two sons. 

PMID- 24591389
TI  - Generalised weakness in a young patient: a cause for concern?
AB  - Muscular weakness in young patients is usually due to mild, self-limiting causes.
      Nonetheless, it is important to remember other, more serious aetiologies which
      can cause this clinical picture. Thyrotoxic hypokalaemic periodic paralysis
      (THPP) is a rare disease in Europe and the USA, with fatal cardiovascular and
      respiratory complications. It is characterised by recurrent episodes of
      generalised muscular weakness, especially in the legs, with an associated
      hypokalaemia and hyperthyroidism. Diagnosis is based on clinical history,
      laboratory tests and an ECG. Early treatment focused on cautious correction blood
      potassium and non-cardiac selective beta-blockers. Additionally, it is imperative
      to normalise thyroid function to prevent relapses. We present a young, healthy
      man to the emergency department with episodes of intermittent leg weakness. The
      history and the ECG findings allowed for the diagnosis of THPP to be reached with
      early treatment causing remission. 

PMID- 24591390
TI  - Opana ER abuse and thrombotic thrombocytopenic purpura (TTP)-like illness: a
      rising risk factor in illicit drug users.
AB  - We report the case of a 22 year-old-woman who presented with upper extremity
      cellulitis secondary to an infiltration of illicit intravenous drug use. She
      confessed to the intravenous use of Opana ER (an extended release oral
      formulation of oxymorphone) which is an opioid drug approved only for oral use.
      She was found to have clinical evidence of profound thrombotic microangiopathy
      which resulted due to the intravenous use of Opana ER. She showed full clinical
      improvement after withholding drug and supportive clinical care. Recent report of
      Opana ER intravenous abuse was published from Tennessee county and has now been
      increasingly recognised as one of the causes of thrombocytopenia which mimicks
      clinically as thrombotic thrombocytopenic purpura. Physicians should be aware of
      this association as the lack of familiarity to this can pose serious management
      dilemmas for our patients (especially the polysubstance abusers). 

PMID- 24591391
TI  - A patient with a red eye and pulmonary oedema.
AB  - A middle-aged black male patient presented with symptoms and radiological
      features indicative of pulmonary oedema. Following several admissions for the
      same symptomology, and poor resolution of chest radiographic features, the
      patient developed a red eye. The latter was diagnosed as uveitis, which prompted
      consideration and proof of a diagnosis of cardiopulmonary sarcoidosis. The
      patient was subsequently treated with high dose steroids resulting in a partial
      recovery, complicated by issues of fluid retention. 

PMID- 24591392
TI  - Anatomy and histology of the Fibrocartilago humerocapsularis in some species of
      European wild birds.
AB  - The occurrence and structure of the fibrocartilago humerocapsularis (FHC) in the
      shoulders of 72 subjects of various species of wild birds were evaluated by gross
      dissection and histological examination with the purpose of increasing the body
      of knowledge regarding this structure and verifying the functional hypotheses
      submitted in the past in other species. The results showed that the FHC has a
      conical shape with a narrow cavity on the inside. The structure is heterogeneous
      in the various species and consists of different tissues, such as hyaline
      cartilage, fibrous cartilage, and bone. From the data obtained in this study,
      there does not appear to be any correlation between ossification and the weight
      of the prey lifted, wing shape, and aging. This study also provided interesting
      preliminary data regarding the ossification of the FHC. In fact, in the Hooded
      Crow (Corvus cornix), the ossification seemed to be correlated with the
      mechanical stimulation of flying. Additional studies are necessary to confirm
      this hypothesis.

PMID- 24591397
TI  - Bis(pentafluorosulfanyl)phenyl azide as an expeditious tool for click chemistry
      toward antitumor pharmaceuticals.
AB  - The inclusion of fluorine in pharmaceutical agents is a well- established means
      of improving their druglike properties. Different substituents have been used to
      introduce fluorine, including trifluoromethyl and trifluoromethylthio groups;
      however, the pentafluorosulfanyl remains relatively underutilized although it is
      considered to be a "super" trifluoromethyl group. Here, a series of
      pentafluorosulfanyl-containing 1,4-disubstituted-1,2,3-triazoles were synthesized
      by click reaction from alkynes and 3,5-bis(pentafluorosulfanyl)phenyl azide in
      excellent yields. Their biological activities were evaluated against human
      leukemic monocyte lymphoma U937 cells. In particular, 1-(3,5
      bis(pentafluorosulfanyl)phenyl)-4-(4-fluorophenyl)-1H-1,2,3-triazole exhibited
      potent efficacy in cell viability assays at a concentration of 60 MUM and was
      shown to activate caspase-3 activity, indicating induction of apoptosis. An
      analogous fluorenol-substituted triazole also exhibited promising cytotoxic
      effects against U937 cells, with an IC50 value of 6.29 MUM. Given these
      preliminary results, these pentafluorosulfanyl-containing triazoles represent
      useful building blocks for the further development of novel antitumor agents.

PMID- 24591398
TI  - Severe mitral regurgitation after intracardiac repair of tetralogy of Fallot: a
      rare complication and management.
AB  - Tetralogy of Fallot (TOF) with additional ventricular septal defect (VSD) forms a
      difficult surgical subset. Commonly, additional VSD is in the muscular septum and
      direct visualization may be difficult during surgical repair especially in
      arrested heart. Consequently, direct closure of these defects is performed based
      upon preoperative imaging and/or intraoperative transoesophageal echocardiogram.
      We hereby report an unforeseen occurrence of traumatic acute severe mitral
      regurgitation after TOF repair possibly during closure of additional muscular
      VSD. We discuss the possible mechanism of this unprecedented complication, which
      was promptly diagnosed and managed with good surgical outcomes.

PMID- 24591399
TI  - A review with meta-analysis of observational studies for survival following off
      pump coronary artery bypass versus drug-eluting stent implantation.
AB  - To determine whether off-pump coronary artery bypass (OPCAB) improves survival
      over drug-eluting stent (DES) implantation, we performed a review with meta
      analysis of exclusive OPCAB versus DES. Databases including MEDLINE, EMBASE and
      the Cochrane Central Register of Controlled Trials were searched through October
      2013 using Web-based search engines (PubMed and OVID). Studies that met the
      following criteria were considered for inclusion: the design was a randomized
      controlled trial or observational comparative study; the study population was
      patients with any coronary artery disease; patients were assigned to OPCAB versus
      DES and outcomes included all-cause mortality at >=1 years. Our exhaustive search
      identified no randomized trial and 10 observational studies of OPCAB versus DES.
      A pooled analysis demonstrated no statistically significant difference in all
      cause mortality between OPCAB and DES (hazard ratio, 0.94; 95% confidence
      interval, 0.76-1.15; P = 0.55). In general, exclusion of any single study from
      the analysis did not substantially alter the overall result of our analysis.
      There was no evidence of significant publication bias. In conclusion, OPCAB may
      not improve survival over DES despite greater number of treated vessels in OPCAB
      than in DES or greater number of distal anastomosis in OPCAB than that of
      implanted stents in DES.

PMID- 24591400
TI  - In endovascular aneurysm repair cases, when should you consider internal iliac
      artery embolization when extending a stent into the external iliac artery?
AB  - A best evidence topic was constructed according to a structured protocol. The
      question addressed was whether internal iliac artery (IIA) embolization is
      necessary for achieving the best clinical outcome in all patients when extension
      of the stent graft to the external iliac artery is required. Altogether more than
      400 papers were found using the reported search, of which 5 represented the best
      evidence to answer the clinical question. The authors, journal, date and country
      of publication, patient group studied, study type, relevant outcomes and results
      of these papers are tabulated. There is a significant gap in the current
      literature regarding the subset of patients that may benefit from an IIA
      embolization during endovascular aneurysm repair (EVAR) as indications have not
      been clearly defined. There are several situations concerning a small number of
      patients, that IIA embolization might be beneficial in preventing endoleak not
      only to the common iliac artery but also to the aortic aneurysmal sac. For the
      majority of patients requiring extension of the stent graft to the external iliac
      artery, the current evidence, even retrospective in nature and reporting on small
      numbers of patients, shows that IIA embolization seems to be associated with
      worse clinical outcome, mostly raising the risk for new-onset buttock
      claudication. It seems that not all patients require embolization, as IIA
      coverage solely by the stent graft was not associated with a significant higher
      rate of type II endoleak in either study. Furthermore, coil embolization in the
      largest study so far was associated with higher procedure and fluoroscopy time
      and amount of contrast media, facts that should not be neglected. However the
      above-mentioned results should be taken into account with caution, as all studies
      were retrospective and reported on small number of patients.

PMID- 24591401
TI  - Capacitance of p- and n-doped graphenes is dominated by structural defects
      regardless of the dopant type.
AB  - Graphene materials possess attractive properties that can be used for the
      fabrication of supercapacitors with enhanced energy-storage performance. It has
      been shown that both boron and nitrogen doping of graphene can improve the
      intrinsic capacitance of the material relative to the undoped precursor. We
      address the question of whether p-doping (using boron as dopant) or n-doping
      (using nitrogen as dopant) leads to increased capacitance relative to undoped
      graphene materials. Using thermal exfoliation we synthesized both boron- and
      nitrogen-doped graphene materials and measured capacitance relative to the
      undoped material. After a full characterization by SEM analysis, X-ray
      photoelectron spectroscopy, Raman spectroscopy, gamma-ray activation analysis,
      Brunauer-Emmett-Teller analysis, and electrochemical techniques we demonstrate
      that the doping process does not lead to enhancement of capacitive behavior and
      that the main characteristic influencing capacitance is the presence of
      structural defects within the graphitic structure, independent of doping level.

PMID- 24591402
TI  - Text messaging and improved data help cut missed and cancelled appointments in
      London.

PMID- 24591403
TI  - Pathological characteristics of early to advanced gallbladder carcinoma and
      extrahepatic cholangiocarcinoma.
AB  - Biliary tract cancer (cancer of gallbladder and extrahepatic bile duct) is the
      most common malignancy of the biliary tract, and is considered to be a high-grade
      malignancy. In this study, we reviewed 293 gallbladder cancers and 102 bile duct
      cancers for clarifying growth and invasion of the extrahepatic bile duct cancer.
      Only 10.5% (9/86) of the early gallbladder cancers showed lymphatic invasion, but
      neither venous invasion nor lymph node metastasis was noted in the early cancers.
      70.6% (207/293) of the gallbladder cases were pT2-3 cancers, and frequently
      showed lymphatic/venous/perineural invasion and/or lymph node metastasis. 12.7%
      (13/102) of the extrahepatic bile duct cancers were pTis or pT1 cancers, which
      were categorized as early cancers. Only 15.4% (2/13) of the early cancer showed
      vascular/perineural invasion and/or lymph node metastasis. The majority (87.3%)
      of the extrahepatic bile duct cases was pT2-3 cancers, and frequently showed
      vascular/perineural invasion and/or lymph node metastasis. We also examined
      intramural invasion patterns; i.e. intramural invasion patterns were defined as
      infiltrative growth (IG) type, and destructive growth (DG) type. The overall
      survival rate of the gallbladder cancer patients with the DG type was
      significantly lower than that of the patients with the IG type, associated with
      frequent lymphatic/venous invasion and/or lymph node metastasis. Therefore,
      pathological characteristics are important for clinical manifestation of the
      gallbladder/extrahepatic bile duct cancers. 

PMID- 24591404
TI  - Biocontainment laboratory risk assessment: perspectives and considerations.
AB  - The ability to respond to public health emergencies involving infectious diseases
      as well as our ability to adequately prepare for as yet unknown or unrecognized
      emerging infectious diseases requires suitable facilities within which scientific
      investigations can take place. To ensure the safe conduct of such investigations
      so that laboratory workers and the general public are protected from potential
      consequences of accidental or intentional release of high consequence pathogens,
      special containment facilities have been designed and constructed. Evaluation of
      the adequacy of containment for these types of investigations requires a risk
      assessment (RA) as part of the overall construction project for these types of
      laboratories. A discussion of the RA process along with considerations that
      impact the design of such studies and the overall results is presented. 

PMID- 24591407
TI  - Quantitative analysis of human salivary gland-derived intact proteome using top
      down mass spectrometry.
AB  - There are several notable challenges inherent for fully characterizing the
      entirety of the human saliva proteome using bottom-up approaches, including
      polymorphic isoforms, PTMs, unique splice variants, deletions, and truncations.
      To address these challenges, we have developed a top-down based LC-MS/MS
      approach, which cataloged 20 major human salivary proteins with a total of 83
      proteoforms, containing a broad range of PTMs. Among these proteins, several
      previously reported disease biomarker proteins were identified at the intact
      protein level, such as beta-2 microglobulin. In addition, intact glycosylated
      proteoforms of several saliva proteins were also characterized, including intact
      N-glycosylated protein prolactin inducible protein and O-glycosylated acidic
      protein rich protein. These characterized proteoforms constitute an intact saliva
      proteoform database, which was used for quantitative comparison of intact
      salivary proteoforms among six healthy individuals. Human parotid and
      submandibular/sublingual gland secretion samples (2 MUg of protein each) from six
      healthy individuals were compared using RPLC coupled with the 12T FT-ICR mass
      spectrometer. Significantly different proteoform profiles were resolved with high
      reproducibility between parotid secretion and submandibular/sublingual glands.
      The results from this study provide further insight into the potential mechanisms
      of PTM pathways in oral glandular secretion, expanding our knowledge of this
      complex yet easily accessible fluid. Intact protein LC-MS approach presented
      herein can potentially be applied for rapid and accurate identification of
      biomarkers from only a few microliters of human glandular saliva. 

PMID- 24591408
TI  - The prediction of malignant risk in the category "atypia of undetermined
      significance/follicular lesion of undetermined significance" of the Bethesda
      System for Reporting Thyroid Cytopathology using subcategorization and BRAF
      mutation results.
AB  - BACKGROUND: The "atypia of undetermined significance/follicular lesion of
      undetermined significance" (AUS/FLUS) category in the Bethesda System for
      Reporting Thyroid Cytopathology is a heterogeneous category of cases that are not
      clearly benign or malignant. METHODS: We conducted an analysis of cytologic and
      histologic evaluations of thyroid nodules that had been interpreted as AUS/FLUS
      on fine-needle aspiration (FNA) at a single institution from April 2011 to April
      2012. Those cases were classified into 2 subgroups according to the predominance
      of nuclear atypia (AUS) or microfollicular architecture (FLUS). In addition, for
      a number of these cases, BRAF gene mutation analyses were performed. RESULTS: Of
      6402 thyroid FNAs performed, 431 cases were diagnosed as AUS and 120 as FLUS.
      Follow-up cytologic or histologic outcome data were available for 315 AUS cases
      and 73 FLUS cases. Among AUS cases, 52.7% were malignant on repeat FNA or
      histologic diagnosis. In contrast, for FLUS, 6.8% were malignant on repeat FNA or
      histologic diagnosis. Among AUS/FLUS cases, 147 had adequate BRAF mutation
      analysis, which accompanied the histologic diagnosis. BRAF mutations were found
      in 87 AUS cases, 86 of which were papillary carcinoma. In contrast, there was
      only 1 case of BRAF mutation in FLUS. Correlating molecular results with
      histologic outcome revealed a 98.9% cancer probability for AUS cases with BRAF
      mutation. CONCLUSIONS: The AUS subcategory indicates a higher risk of malignancy
      than the FLUS subcategory. Furthermore, BRAF molecular testing is helpful in
      stratifying the malignant risk of AUS cases into high-risk and low-risk groups.

PMID- 24591409
TI  - The Super Bowl doctor.

PMID- 24591411
TI  - Association of circulating level of high mobility group box 1 with disease
      activity in antineutrophil cytoplasmic autoantibody-associated vasculitis.
AB  - OBJECTIVE: High mobility group box 1 (HMGB-1), a kind of proinflammatory
      mediator, is associated with inflammatory conditions and tissue damage. Previous
      studies have reported that circulating HMGB-1 levels in patients with active
      antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) were
      associated with renal manifestations and burdens of granulomatous inflammation.
      The current study aimed to investigate whether circulating HMGB-1 levels were
      associated with disease activity in AAV. METHODS: Plasma samples from 74 patients
      with AAV in active stage and 65 patients with AAV in remission were collected.
      The plasma levels of HMGB-1 were determined by enzyme-linked immunosorbent assay.
      Associations between plasma levels of HMGB-1 with clinical and pathologic
      parameters were analyzed. RESULTS: Plasma levels of HMGB-1 in active AAV patients
      were significantly higher than those in normal controls and AAV patients in
      remission (median 6.11 [interquartile range (IQR) 3.25-12.79] ng/ml versus median
      1.12 [IQR 0.53-1.39] ng/ml, P< 0.001; median 6.11 [IQR 3.25-12.79] ng/ml versus
      median 3.04 [IQR 1.97-4.63] ng/ml, P < 0.001, respectively). Correlation analysis
      showed that plasma levels of HMGB-1 correlated with initial serum creatinine (r =
      0.275, P = 0.018), estimated glomerular filtration rate (r = -0.277, P = 0.017),
      the Birmingham Vasculitis Activity Score (r = 0.308, P = 0.008), and C-reactive
      protein level (r = 0.309, P = 0.008). Among the patients with myeloperoxidase
      (MPO)-ANCA, those within the first quartile of plasma HMGB-1 levels had a
      significantly lower level of MPO-ANCA than those within the other 3 quartiles.
      CONCLUSION: Circulating HMGB-1 levels might reflect the disease activity and
      renal involvement of AAV vasculitis.

PMID- 24591410
TI  - Associations of foot posture and function to lower extremity pain: results from a
      population-based foot study.
AB  - OBJECTIVE: Studies have implicated foot posture and foot function as risk factors
      for lower extremity pain. Empirical population-based evidence for this assertion
      is lacking; therefore, the purpose of this study was to evaluate cross-sectional
      associations of foot posture and foot function to lower extremity joint pain in a
      population-based study of adults. METHODS: Participants were members of the
      Framingham Foot Study. Lower extremity joint pain was determined by the response
      to the National Health and Nutrition Examination Survey-type question, "On most
      days do you have pain, aching or stiffness in your (hips, knees, ankles, or
      feet)?" The Modified Arch Index classified participants as having planus, rectus
      (referent), or cavus foot posture. The Center of Pressure Excursion Index
      classified participants as having overpronated, normal (referent), or
      oversupinated foot function. Crude and adjusted (age, sex, and body mass index)
      logistic regression determined associations of foot posture and function to lower
      extremity pain. RESULTS: Participants with planus structure had higher odds of
      knee (odds ratio [OR] 1.57, 95% confidence interval [95% CI] 1.24-1.99) or ankle
      (OR 1.47, 95% CI 1.05-2.06) pain, whereas those with a cavus foot structure had
      increased odds of ankle pain only (OR 7.56, 95% CI 1.99-28.8) and pain at 1 lower
      extremity site (OR 1.37, 95% CI 1.04-1.80). Associations between foot function
      and lower extremity joint pain were not statistically significant except for a
      reduced risk of hip pain in those with an oversupinated foot function (OR 0.69,
      95% CI 0.51-0.93). CONCLUSION: These findings offer a link between foot posture
      and lower extremity pain, highlighting the need for longitudinal or intervention
      studies.

PMID- 24591412
TI  - A patient with hepatitis C virus infection and inflammatory polyarthritis.

PMID- 24591413
TI  - Tumor necrosis factor, tuberculosis, testing, and treatment: teeing up the
      questions.

PMID- 24591414
TI  - Organocatalytic asymmetric Friedel-Crafts reaction of sesamol with isatins:
      access to biologically relevant 3-aryl-3-hydroxy-2-oxindoles.
AB  - The Friedel-Crafts reaction of electron-rich phenols with isatins was developed
      by employing bifunctional thiourea-tertiary amine organocatalysts. Cinchona
      alkaloid derived thiourea epiCDT-3 a efficiently catalyzed the Friedel-Crafts
      type addition of phenols to isatin derivatives to provide 3-aryl-3-hydroxy-2
      oxindoles 7 and 9 in good yield (80-95 %) with good enantiomeric excess (83-94
      %). Friedel-Crafts adduct 7 t was subjected to a copper(I)-catalyzed azide-alkyne
      cycloaddition to obtain biologically important 3-aryl-3-hydroxy-2-oxindole 11 in
      good enantiomeric excess and having a 1,2,3-triazole moiety. 

PMID- 24591416
TI  - Latent protective effects of breastfeeding on late childhood overweight and
      obesity: a nationwide prospective study.
AB  - OBJECTIVE: To investigate the latent effect of breastfeeding on overweight and
      obesity in late childhood. METHODS: Data on breastfeeding and child
      anthropometric measurements were collected annually from a nation-wide population
      based prospective cohort study in Japan (21,425 boys and 20,147 girls).
      Breastfeeding status (exclusiveness and duration) was assessed when the child was
      6 months old. Mixed effects models were used to evaluate trajectories of body
      mass index (BMI), together with overweight and obesity status, from 1.5 to 8
      years of age. RESULTS: Mixed-fed boys and exclusively breastfed boys showed lower
      BMI as the main effect, as well as a slower increase of inclination in BMI as
      interaction term between feeding type and age, than exclusively formula-fed boys.
      Breastfed boys had lower BMI at the ages of 7 and 8, in comparison with
      exclusively formula fed boys (P = 0.002 and P < 0.001, respectively). A similar
      association was found for girls, although the main effect of feeding type was not
      statistically significant. The analysis of breastfeeding duration had similar
      results. CONCLUSIONS: Breastfeeding, even if partial or for short duration, has a
      latent protective effect against overweight and obesity in late childhood,
      especially for boys.

PMID- 24591415
TI  - CGG allele size somatic mosaicism and methylation in FMR1 premutation alleles.
AB  - BACKGROUND: Greater than 200 CGG repeats in the 5'UTR of the FMR1 gene lead to
      epigenetic silencing and lack of the FMR1 protein, causing fragile X Syndrome.
      Individual carriers of a premutation (PM) allele with 55-200 CGG repeats are
      typically unmethylated and can present with clinical features defined as FMR1
      associated conditions. METHODS: Blood samples from 17 male PM carriers were
      assessed clinically and molecularly by Southern blot, western blot, PCR and QRT
      PCR. Blood and brain tissue from an additional 18 PM males were also similarly
      examined. Continuous outcomes were modelled using linear regression and binary
      outcomes were modelled using logistic regression. RESULTS: Methylated alleles
      were detected in different fractions of blood cells in all PM cases (n=17). CGG
      repeat numbers correlated with percent of methylation and mRNA levels and,
      especially in the upper PM range, with greater number of clinical involvements.
      Inter-tissue/intra-tissue somatic instability and differences in percent
      methylation were observed between blood and fibroblasts (n=4) and also observed
      between blood and different brain regions in three of the 18 PM cases examined.
      CGG repeat lengths in lymphocytes remained unchanged over a period of time
      ranging from 2 to 6 years, three cases for whom multiple samples were available.
      CONCLUSIONS: In addition to CGG size instability, individuals with a PM expanded
      allele can exhibit methylation and display more clinical features likely due to
      RNA toxicity and/or FMR1 silencing. The observed association between CGG repeat
      length and percent of methylation with the severity of the clinical phenotypes
      underscores the potential value of methylation in affected PM to further
      understand penetrance, inform diagnosis and expand treatment options.

PMID- 24591417
TI  - Cystic pancreatic neuroendocrine tumors: the value of cytology in preoperative
      diagnosis.
AB  - BACKGROUND: Cystic pancreatic neuroendocrine tumors (cPanNETs) account for 13% to
      17% of PanNETs. Although the value of endoscopic ultrasound (EUS) imaging and
      cyst fluid analysis (CFA) in their preoperative diagnosis has been well
      described, limited information is available about the diagnostic role of cytology
      samples obtained from fine-needle aspiration (FNA). METHODS: Cytopathology
      records between 1992 and 2013 were searched for all reports of cysts interpreted
      as PanNET. Patient demographics, clinical and radiologic information, CFA,
      histopathology, and cytopathology findings were recorded. Performance
      characteristics of cytology and EUS for the accurate diagnosis of cPanNET were
      calculated. RESULTS: In total, 35 FNAs from 33 patients with cPanNETs were
      identified, and 34 EUS were performed. Cytology made a specific diagnosis of a
      cPanNET in 71% of the biopsies compared with a specific diagnosis by EUS in 38%
      of cases. An interpretation of suspicious for cPanNET was given in 77% of cases
      by cytology and in 47% by EUS. Cytology identified 86% of the lesions as high
      risk pancreatic cysts compared with 56% by EUS. Diagnostic morphology was present
      on both cytology and cell block preparations in 60% of aspirates, on cytology
      only in 20%, and on cell block only in 20%. CFA was performed on 51% cyst fluids.
      All cysts but 1 revealed low carcinoembryonic antigen levels (range, 0.2 to >500
      ng/mL; mean, 29.5 ng/mL), and amylase levels were <500 U/L in all but 2 cases
      (range, 16-1493 U/L; mean, 205 U/L). CONCLUSIONS: Cytology is the most accurate
      test for preoperative diagnosis of cPanNETs. EUS is insufficiently accurate for
      independent diagnosis, and carcinoembryonic antigen and amylase analyses are
      noncontributory.

PMID- 24591418
TI  - Recognizing the scale of joint hypermobility burden: comment on the article by
      Mulvey et al.

PMID- 24591421
TI  - Vicinal difunctionalization of alkenes with iodine(III) reagents and catalysts.
AB  - Hypervalent iodine(III) reagents have been known for over a century, and their
      reaction profile is still actively investigated. Recent years have seen
      impressive improvements in the area of alkene difunctionalization reactions,
      where new methodologies have become available. Especially chiral non-racemic
      hypervalent iodine(III) reagents and catalysts have emerged as versatile tools
      for the realization of important enantioselective transformations. 

PMID- 24591422
TI  - FDA is urged to reverse its approval of new pain drug Zohydro ER.

PMID- 24591423
TI  - Aggregicoccus edonensis gen. nov., sp. nov., an unusually aggregating
      myxobacterium isolated from a soil sample.
AB  - A novel myxobacterium, MCy1366(T) (Ar1733), was isolated in 1981 from a soil
      sample collected from a region near Tokyo, Japan. It displayed general
      myxobacterial features like Gram-negative-staining, rod-shaped vegetative cells,
      gliding on solid surfaces, microbial lytic activity, fruiting-body-like
      aggregates and myxospore-like structures. The strain was mesophilic, aerobic and
      showed a chemoheterotrophic mode of nutrition. It was resistant to many
      antibiotics such as cephalosporin C, kanamycin, gentamicin, hygromycin B,
      polymyxin and bacitracin, and the key fatty acids of whole cell hydrolysates were
      iso-C15 : 0, iso-C17 : 0 and iso-C17 : 0 2-OH. The genomic DNA G+C content of the
      novel strain was 65.6 mol%. The 16S rRNA gene sequence showed highest similarity
      (97.60 %) to 'Stigmatella koreensis' strain KYC-1019 (GenBank accession no.
      EF112185). Phylogenetic analysis based on 16S rRNA gene sequences and MALDI-TOF
      MS data revealed a novel branch in the family Myxococcaceae. DNA-DNA
      hybridization showed only 28 % relatedness between the novel strain and the
      closest recognized species, Corallococcus exiguus DSM 14696(T) (97 % 16S rRNA
      gene sequence similarity). A recent isolate from a soil sample collected in
      Switzerland, MCy10622, displayed 99.9 % 16S rRNA gene sequence similarity with
      strain MCy1366(T) and showed almost the same characteristics. Since some
      morphological features like fruiting-body-like aggregates were barely
      reproducible in the type strain, the newly isolated strain, MCy10622, was also
      intensively studied. On the basis of a comprehensive taxonomic study, we propose
      a novel genus and species, Aggregicoccus edonensis gen. nov., sp. nov., for
      strains MCy1366(T) and MCy10622. The type strain of the type species is
      MCy1366(T) ( = DSM 27872(T) = NCCB 100468(T)). 

PMID- 24591424
TI  - Melaminivora alkalimesophila gen. nov., sp. nov., a melamine-degrading
      betaproteobacterium isolated from a melamine-producing factory.
AB  - A taxonomic study was carried out on strain CY1(T), which is a novel bacterium
      isolated from wastewater sludge of a melamine-producing factory in Sanming city,
      Fujian, China. Strain CY1(T) was shown to rapidly and completely degrade melamine
      to NH3 and CO2 under aerobic conditions. The isolate was Gram-stain-negative,
      short-rod-shaped and motile by one unipolar flagellum. Growth was observed at
      salinities from 0 to 7% NaCl (optimum, 0.1%), at temperatures from 15 to 50 
      degrees C (optimum, 40-45  degrees C) and at pH 7-9.5 (optimum pH 9.5). Quinone-8
      was detected as the major respiratory quinone. 16S rRNA gene sequence comparisons
      showed that strain CY1(T) was affiliated to the family Comamonadaceae in the
      class Betaproteobacteria. It was most closely related to members of the genera
      Alicycliphilus (95.5%), Diaphorobacter (94.6-95.1%), Acidovorax (92.9-95.4%),
      Delftia (93.0-93.6%) and Comamonas (92.6-93.9%). The average nucleotide identity
      (ANI) values between strain CY1(T) and those representing related genera ranged
      from 84.0 to 86.1% using Mummer, and from 74.9 to 81.1% using BLAST. The dominant
      fatty acids were C(16 : 1)omega7c and/or C(16 : 1)omega6c, C(16 : 0), C(10 : 0) 3
      OH and C(18 : 1)omega7c and/or C(18 : 1)omega6c, and the major polar lipids
      consisted of phosphatidylethanolamine, diphosphatidylglycerol,
      phosphatidylglycerol, one unidentified phospholipid and one unidentified
      aminophospholipid. The G+C content of the chromosomal DNA was 69.5 mol%. On the
      basis of the phenotypic and phylogenetic data, strain CY1(T) represents a novel
      species of a new genus, for which the name Melaminivora alkalimesophila gen.
      nov., sp. nov. is proposed. The type strain of Melaminivora alkalimesophila is
      CY1(T) ( = CCTCC AB 2012024(T) = DSM 26006(T)).

PMID- 24591425
TI  - The art of communication.

PMID- 24591426
TI  - Do Social Stories help to decrease disruptive behaviour in children with autistic
      spectrum disorders? A review of the published literature.
AB  - A structured search and identification of themes within the literature regarding
      the use of Social Stories to decrease disruptive behaviour in children with
      autistic spectrum disorders is presented. The examination of seven studies showed
      that the Social Story intervention was successful for the majority of the
      participants, although the level of success was variable. Overall, Social Stories
      appear to be an acceptable intervention for use in the classroom, however
      unplanned verbal prompting by teachers, in some studies, reduced confidence in
      the effectiveness of Social Stories when used in isolation. An increasing body of
      literature has indicated that Social Stories are an effective intervention for
      children diagnosed with autistic spectrum disorders, however very few studies
      have addressed the efficacy of Social Stories when used with children with other
      disabilities. 

PMID- 24591427
TI  - Cancer screening in women with intellectual disabilities: an Irish perspective.
AB  - In the Republic of Ireland, more than 8000 women with intellectual disabilities
      (IDs), aged 20 years and over, are registered for service provision. Their health
      needs challenge preventative health services including breast and cervical cancer
      screening programmes. This review explores the literature about cancer screening
      participation rates and issues related to screening for Irish women with IDs. Low
      cancer screening participation rates are evident in Irish women with IDs; and the
      women shed light on the barriers they perceive related to the screening
      experience. These experiences are reflected in the international literature for
      women with IDs. Further research involving the assessment of the breast and
      cervical cancer awareness in Irish women with IDs and their participation in
      cancer screening programmes is recommended. Strategies are required to increase
      their participation in screening programmes that may lead to the earlier
      diagnosis with better outcomes. 

PMID- 24591428
TI  - Enhancing activity by means of tactile symbols: a study of a heterogeneous group
      of pupils with congenital blindness, intellectual disability and autism spectrum
      disorder.
AB  - This study investigates responses to verbal versus tactile requests in children
      with congenital blindness, intellectual disability and autism spectrum disorder
      (ASD). Observation was conducted on two occasions. At T1, requests were given
      verbally, and at T2, tactile requests were given. All pupils perceived tactile
      symbols to be explicit requests to perform the act referred to by the symbols.
      The children seldom or never followed verbal requests. All children followed more
      tactile than verbal requests. Individual differences in verbal skills,
      motivations and the complexity of the activity are discussed. The availability of
      tactile symbols for individuals with congenital blindness, intellectual
      disability and ASD seems to increase their level of activity and their
      participation in school. 

PMID- 24591429
TI  - Brucellosis in dairy cattle and goats in northern Ecuador.
AB  - The purpose of this study was to conduct a convenience study for brucellosis
      prevalence in dairy-producing animals in northern Ecuador. In total, 2,561 cows
      and 301 goats were tested. Cattle sera were tested using the Rose Bengal card
      antigen test (RBCT), yielding an overall apparent prevalence of 5.5% (95%
      confidence interval [95% CI] = 4.7-6.5%) and true prevalence of 7.2% (95% CI =
      6.0-8.5%). Prevalence varied by herd size and was highest in larger commercial
      herds. Polymerase chain reaction was used to test goat milk and lymph nodes,
      resulting in 9% and 8% positivity, respectively. The RBCTs from goat sera yielded
      an adjusted true prevalence of 17.8% (95% CI = 6.2-44.2%). Our findings are
      similar to other overall prevalence estimates for dairy herds but show higher
      prevalence in commercial herds compared with small groups (less than five
      animals). We also identify urban milking goats living in metropolitan Quito as a
      potential source of zoonosis.

PMID- 24591430
TI  - Longitudinal evaluation of enteric protozoa in Haitian children by stool exam and
      multiplex serologic assay.
AB  - Haitian children were monitored longitudinally in a filariasis study. Included
      were stool samples examined for Giardia intestinalis and Entamoeba histolytica
      cysts, and serum specimens analyzed for immunoglobulin G (IgG) responses to eight
      recombinant antigens from G. intestinalis (variant-specific surface protein [VSP1
      VSP5]), E. histolytica (lectin adhesion molecule [LecA]), and Cryptosporidium
      parvum (17- and 27-kDa) using a multiplex bead assay. The IgG responses to VSP
      antigens peaked at 2 years of age and then diminished and were significantly
      lower (P < 0.002) in children > 4.5 years than in children < 4.5 years. The IgG
      responses to Cryptosporidium tended to increase with age. The IgG responses to
      LecA and VSP antigens and the prevalence of stools positive for cysts were
      significantly higher (P < 0.037 and P < 0.035, respectively) in the rainy season
      than in the dry season. The multiplex bead assay provides a powerful tool for
      analyzing serologic responses to multiple pathogens.

PMID- 24591431
TI  - Performance of point-of-care diagnostics for glucose, lactate, and hemoglobin in
      the management of severe malaria in a resource-constrained hospital in Uganda.
AB  - Severe malaria is frequently managed without access to laboratory testing. We
      report on the performance of point-of-care tests used to guide the management of
      a cohort of 179 children with severe malaria in a resource-limited Ugandan
      hospital. Correlation coefficients between paired measurements for glucose (i
      STAT and One Touch Ultra), lactate (i-STAT and Lactate Scout), and hemoglobin
      (Hb; laboratory and i-STAT) were 0.86, 0.85, and 0.73, respectively. The OneTouch
      Ultra glucometer readings deviated systematically from the i-STAT values by +1.7
      mmol/L. Lactate Scout values were systematically higher than i-STAT by +0.86
      mmol/L. Lactate measurements from either device predicted subsequent mortality.
      Hb estimation by the i-STAT instrument was unbiased, with upper and lower limits
      of agreement of -34 and +34 g/L, and it was 91% sensitive and 89% specific for
      the diagnosis of severe anemia (Hb < 50 g/L). New commercially available bedside
      diagnostic tools, although imperfect, may expedite clinical decision-making in
      the management of critically ill children in resource-constrained settings.

PMID- 24591432
TI  - Dosing of praziquantel by height in sub-Saharan African adults.
AB  - The cornerstone of schistosomiasis control is mass praziquantel treatment in high
      prevalence areas. Adults are an important target population, given increasing
      recognition of the burden of male and female genital schistosomiasis. However,
      use of weighing scales to calculate praziquantel dosing in rural areas can be
      challenging. For school-age children, the World Health Organization (WHO) has
      approved a dose pole to simplify praziquantel dosing based on height. We modified
      the pediatric dose pole by adding two height categories and incorporating a
      simple overweight/obesity adjustment, for simplified mass treatment of adults in
      sub-Saharan Africa. Using the rural Zimbabwean Demographic and Health Survey
      data, we show that the modified dose pole with body mass index adjustment would
      result in > 98% of adults receiving an acceptable dose (30-60 mg/kg), with only
      1.4% and 0.3% receiving an inadequate dose (< 30 mg/kg) or high dose (> 60
      mg/kg), respectively. An adult dose pole may provide a more feasible alternative
      to weighing scales in community-based praziquantel treatment programs.

PMID- 24591433
TI  - Molecular detection of hepatitis E virus in rivers in the Philippines.
AB  - To understand the hepatitis E virus (HEV)-pollution status in the environment in
      the Philippines, a total of 12 water samples were collected from rivers in Manila
      City for detection of HEV RNA. Three of 12 samples were positive for HEV RNA
      indicating that HEV is circulating in the Philippines. Phylogenetic analysis
      classified all of the HEV sequences into genotype 3.

PMID- 24591434
TI  - Salmonella typhi liver abscess overlying a metastatic melanoma.
AB  - Pyogenic liver abscesses caused by Salmonella enterica serotype Typhi, although
      rare, can occur especially in patients with pre-existing hepatobiliary disease,
      hepatocellular carcinoma, and metastatic liver tumors. We present a case of
      Salmonella liver abscesses complicating metastatic melanoma in a 24-year-old
      alcoholic male.

PMID- 24591435
TI  - Meteorological variables and bacillary dysentery cases in Changsha City, China.
AB  - This study aimed to investigate the association between meteorological-related
      risk factors and bacillary dysentery in a subtropical inland Chinese area:
      Changsha City. The cross-correlation analysis and the Autoregressive Integrated
      Moving Average with Exogenous Variables (ARIMAX) model were used to quantify the
      relationship between meteorological factors and the incidence of bacillary
      dysentery. Monthly mean temperature, mean relative humidity, mean air pressure,
      mean maximum temperature, and mean minimum temperature were significantly
      correlated with the number of bacillary dysentery cases with a 1-month lagged
      effect. The ARIMAX models suggested that a 1 degrees C rise in mean temperature,
      mean maximum temperature, and mean minimum temperature might lead to 14.8%,
      12.9%, and 15.5% increases in the incidence of bacillary dysentery disease,
      respectively. Temperature could be used as a forecast factor for the increase of
      bacillary dysentery in Changsha. More public health actions should be taken to
      prevent the increase of bacillary dysentery disease with consideration of local
      climate conditions, especially temperature.

PMID- 24591436
TI  - After malaria is controlled, what's next?

PMID- 24591437
TI  - Biochemical and hematologic parameters for children in the middle belt of Ghana.
AB  - Reference values derived from developed countries are used in many countries in
      Africa for interpretation of laboratory results obtained during routine
      healthcare and clinical trials. Use of locally derived reference values has been
      recommended. The purpose of the study was to establish age- and sex-specific
      reference values for children in the middle belt of Ghana. Reference values were
      determined for 21 biochemical and 18 hematologic parameters by using Clinical and
      Laboratory Standards Institute C28-A3 guidelines in a sample of 1,442 healthy
      children. Hemoglobin, hematocrit, mean cell volume, erythrocytes, urea, and
      creatinine were lower when compared with values from northern countries but
      alanine aminotransferase, aspartate aminotransferase, and total bilirubin were
      higher. A panel of locally relevant age- and sex-specific reference values was
      established for commonly used biochemical and hematologic tests in children in
      the middle part of Ghana. This will help in interpretation of laboratory results
      for clinical management of patients, screening, and safety monitoring during
      clinical trials.

PMID- 24591438
TI  - Response to the critique by Hahn and others entitled "Conservation and malaria in
      the Brazilian Amazon".
AB  - Hahn and others have recently criticized our study, "Conservation efforts may
      increase malaria burden in the Brazilian Amazon," suggesting that results were
      flawed because of methodological limitations. Here, we briefly comment on some of
      their claims, showing that (1) several of their criticisms are misleading and
      others are incorrect, (2) they heavily criticize methods that they themselves
      have previously used, and (3) they selectively highlight some findings while
      ignoring others. We end this rebuttal by suggesting a way forward in this debate.

PMID- 24591439
TI  - Treatment of suspected hyper-reactive malarial splenomegaly (HMS) in pregnancy
      with mefloquine.
AB  - Malaria infections in pregnancy are associated with adverse outcomes for both
      mother and child. There are few data on hyper-reactive malarial splenomegaly, an
      aberrant immunological response to chronic or recurrent malaria in pregnancy.
      This retrospective assessment reviewed the impact of mefloquine treatment on
      pregnant women with suspected hyper-reactive malarial splenomegaly in an area of
      low malaria transmission in the 1990s, showing significant reductions in spleen
      size and anemia and anti-malarial antibody titers without any notable negative
      effect on treated women or their newborns.

PMID- 24591440
TI  - Expression pattern analysis of odorant-binding proteins in the pea aphid
      Acyrthosiphon pisum.
AB  - Odorant-binding proteins (OBPs) are soluble proteins mediating chemoreception in
      insects. In previous research, we investigated the molecular mechanisms adopted
      by aphids to detect the alarm pheromone (E)-beta-farnesene and we found that the
      recognition of this and structurally related molecules is mediated by OBP3 and
      OBP7. Here, we show the differential expression patterns of 5 selected OBPs
      (OBP1, OBP3, OBP6, OBP7, OBP8) obtained performing quantitative RT-PCR and
      immunolocalization experiments in different body parts of adults and in the 5
      developmental instars, including winged and unwinged morphs, of the pea aphid
      Acyrthosiphon pisum. The results provide an overall picture that allows us to
      speculate on the relationship between the differential expression of OBPs and
      their putative function. The expression of OBP3, OBP6, and OBP7 in the antennal
      sensilla suggests a chemosensory function for these proteins, whereas the
      constant expression level of OBP8 in all instars could suggest a conserved role.
      Moreover, OBP1 and OBP3 are also expressed in nonsensory organs. A light and
      scanning electron microscopy study of sensilla on different body parts of aphid,
      in particular antennae, legs, mouthparts, and cornicles-cauda, completes this
      research providing a guide to facilitate the mapping of OBP expression profiles. 

PMID- 24591441
TI  - Use of conventional smears versus liquid-based preparations for fine-needle
      aspirate specimens: the time has not come to abandon your conventional smears!

PMID- 24591442
TI  - The dilemma of medical marijuana use by rheumatology patients.

PMID- 24591443
TI  - Enhanced photocatalytic hydrogen evolution over hierarchical composites of ZnIn2
      S4 nanosheets grown on MoS2 slices.
AB  - A highly active hierarchical MoS2/ZnIn2S4 composite catalyst was synthesized in
      situ by using a facile controlled-growth approach through a solvothermal process.
      During the solvothermal reaction, 2D ultrathin curled ZnIn2S4 nanosheets grew on
      the surface of MoS2 slices, which could help to form a more-homogeneous mixture,
      effective interfacial contact, and strong interactions between the ZnIn2S4
      nanosheets and the MoS2 slices. The intimate contact between ZnIn2S4 and MoS2
      favored the formation of junctions between the two components, thereby improving
      the charge separation and prolonging the mean lifetime of the electron-hole
      pairs. Moreover, growing ZnIn2S4 nanosheets by visible-light catalysis on MoS2
      slices afforded a higher number of available catalytically active sites. So, the
      photocatalytic hydrogen-evolution performance of the hierarchical MoS2/ZnIn2S4
      composite was significantly enhanced, owing to a synergistic effect of these
      factors. This work could provide new insights into the fabrication of a highly
      efficient and low-cost non-noble-metal co-catalyst for visible-light H2
      generation.

PMID- 24591444
TI  - Antiapoptotic activity of 30 kDa lipoproteins family from fat body tissue of
      silkworm, Bombyx mori.
AB  - The family of 30 kDa lipoproteins (LP1-5) is abundant in silkworm pupa fat body
      (FB) and hemolymph. One of its members, the 29 kDa protein decreased in
      concentration from peripheral (PP) FB tissue but was sustained in perivisceral
      (PV) FB tissue at the time of apoptosis. This study investigated the correlation
      of the 30 kDa proteins with FB apoptosis. Two protein fractions were purified, a
      29 and a 30/31 kDa protein fraction, and they were used to test for activity
      against actinomycin D-induced apoptosis in the FB tissues. Concentrations as
      little as 50 MUg/mL of the 29 kDa protein fraction efficiently inhibited
      apoptosis. Less antiapoptotic activity was detected for the higher MW fraction;
      DNA fragmentation was observed in FB tissue treated with 50 MUg/mL of the 30/31
      kDa fraction. The viability of the cells in the 29 kDa protein-supplemented
      culture was 40% higher than in the 31 kDa protein-supplemented culture. However,
      the 30 kDa lipoproteins were not able to prevent scheduled FB degeneration during
      silkworm metamorphosis. Thus, it is hypothesized that the antiapoptotic 29 kDa
      protein needs to be proteolytically degraded by a regulatory mechanism to allow
      programmed cell death of FB tissue.

PMID- 24591445
TI  - Financial donors warn Ugandan government over anti-gay law.

PMID- 24591446
TI  - Who was responsible for reaching the Americas-Columbus or his ships?: Focusing on
      the side of liquid-based cytology: the importance and role of the cytopathologist
      as opposed to the cytological method used.

PMID- 24591447
TI  - Validation of a home safety questionnaire used in a series of case-control
      studies.
AB  - OBJECTIVE: To measure the validity of safety behaviours, safety equipment use and
      hazards reported on a questionnaire by parents/carers with children aged under 5
      years participating in a series of home safety case-control studies. METHODS: The
      questionnaire measured safety behaviours, safety equipment use and hazards being
      used as exposures in five case-control studies. Responses to questions were
      compared with observations made during a home visit. The researchers making
      observations were blind to questionnaire responses. RESULTS: In total, 162
      families participated in the study. Overall agreement between reported and
      observed values of the safety practices ranged from 48.5% to 97.3%. Only 3 safety
      practices (stair gate at the top of stairs, stair gate at the bottom of stairs,
      stairs are carpeted) had substantial agreement based on the kappa statistic
      (k=0.65, 0.72, 0.74, respectively). Sensitivity was high (>=70%) for 19 of the 30
      safety practices, and specificity was high (>=70%) for 20 of the 30 practices.
      Overall for 24 safety practices, a higher proportion of respondents over-reported
      than under-reported safe practice (negative predictive value>positive predictive
      value). For six safety practices, a higher proportion of respondents under
      reported than over-reported safe practice (negative predictive value<positive
      predictive value). CONCLUSIONS: This study found that the validity of self
      reports varied with safety practice. Questions with a high specificity will be
      useful for practitioners for identifying households who may benefit from home
      safety interventions and will be useful for researchers as measures of exposures
      or outcomes.

PMID- 24591454
TI  - Stereogenic phosphorus-induced diastereoselective formation of chiral carbon
      during nucleophilic addition of chiral H-P species to aldehydes or ketones.
AB  - P,C-stereogenic alpha-hydroxyl phosphinates or phosphine oxides were prepared
      from the additions of (RP)-phosphinate to ketones or (RP)-phosphine oxide to
      aldehydes, respectively, catalyzed by bases at room temperature in up to >99:1
      diasteromeric ratio (d.r.P/d.r.C) and 99 % yields. The diastereoselectivity was
      induced by reversible equilibrium and different stabilities between two
      diastereomers of adduct, which was caused by the spatial interaction between
      menthoxyl or menthyl to alkyl groups of aldehydes or ketones.

PMID- 24591455
TI  - Deep brain stimulation surgery under general anaesthesia with microelectrode
      recording: the best of both worlds or a little bit of everything?

PMID- 24591453
TI  - Recasting the theory of mosquito-borne pathogen transmission dynamics and
      control.
AB  - Mosquito-borne diseases pose some of the greatest challenges in public health,
      especially in tropical and sub-tropical regions of the world. Efforts to control
      these diseases have been underpinned by a theoretical framework developed for
      malaria by Ross and Macdonald, including models, metrics for measuring
      transmission, and theory of control that identifies key vulnerabilities in the
      transmission cycle. That framework, especially Macdonald's formula for R0 and its
      entomological derivative, vectorial capacity, are now used to study dynamics and
      design interventions for many mosquito-borne diseases. A systematic review of 388
      models published between 1970 and 2010 found that the vast majority adopted the
      Ross-Macdonald assumption of homogeneous transmission in a well-mixed population.
      Studies comparing models and data question these assumptions and point to the
      capacity to model heterogeneous, focal transmission as the most important but
      relatively unexplored component in current theory. Fine-scale heterogeneity
      causes transmission dynamics to be nonlinear, and poses problems for modeling,
      epidemiology and measurement. Novel mathematical approaches show how
      heterogeneity arises from the biology and the landscape on which the processes of
      mosquito biting and pathogen transmission unfold. Emerging theory focuses
      attention on the ecological and social context for mosquito blood feeding, the
      movement of both hosts and mosquitoes, and the relevant spatial scales for
      measuring transmission and for modeling dynamics and control.

PMID- 24591456
TI  - Neurological picture. Pure motor monoparesis of the leg after carbon monoxide
      intoxication.

PMID- 24591457
TI  - Heterozygous D90A-SOD1 mutation in a patient with facial onset sensory motor
      neuronopathy (FOSMN) syndrome: a bridge to amyotrophic lateral sclerosis.
AB  - OBJECTIVE: To describe a patient with facial onset sensory motor neuronopathy
      (FOSMN) syndrome associated with a heterozygous D90A mutation in superoxide
      dismutase (SOD1) gene. METHODS: The patient underwent neurological and
      neurophysiologic examinations, including blink and jaw reflexes, sural nerve and
      skin biopsies, and analysis of TARDBP, FUS and C9ORF72 genes. RESULTS:
      Neurological examination showed diffuse fasciculations, bulbar signs, hypotrophy
      and weakness of facial, neck, shoulder girdle and first interosseus muscles, and
      absent corneal reflex. Neurophysiologic studies demonstrated abnormal blink and
      jaw reflexes and reduced sensory nerve action potentials at upper limbs. Sural
      nerve and skin biopsies revealed mild loss of large and small nerve fibres.
      Genetic analysis demonstrated a heterozygous D90A-SOD1 mutation. CONCLUSIONS:
      FOSMN syndrome has been recently described in patients with slowly progressive
      bulbar and upper limb amyotrophy. Sensory symptoms, mainly involving the
      trigeminal territory, typically precede the onset of motor weakness by months or
      years. The pathogenesis of FOSMN syndrome is unknown and possible immune-mediated
      mechanisms have been claimed. Our findings support the hypothesis that FOSMN
      syndrome is a primary degenerative disorder that widens the spectrum of motor
      neuron diseases.

PMID- 24591458
TI  - The impact and prognosis for dystonia in childhood including dystonic cerebral
      palsy: a clinical and demographic tertiary cohort study.
AB  - INTRODUCTION AND METHODS: The impact of dystonia in childhood is poorly
      understood. We report our experience of referrals between 2005 and 2012. RESULTS:
      Of 294/315 assessable children, 15/294 had pure spasticity, leaving 279/294 with
      dystonia classified as primary (30/279:10.7%); primary-plus (19/279:6.8%) and
      secondary (230/279:82.4%) dystonia, including heredodegenerative dystonia
      (29/279:10.3%); 150/279 (53.7%) with cerebral palsy and 51/279 (18.2%) acquired
      brain injury. Definitive diagnoses were available in 222/294 (79.6%), but lower
      in primary/primary-plus compared with secondary groups (11/49 vs 211/230:
      Fisher's exact test p<0.0001). Spasticity comorbidity was present in 79/230
      (34.3%) children. Median age (interquartile years) at referral was 9.75 (6.58
      13), not significantly differing by aetiology (Kruskal-Wallis test p>0.05);
      dystonia-onset age was 3 (0.5-7.0) for primary/primary-plus and 0.25 (0.08-0.8)
      in the secondary/CP groups. Dystonia duration at referral was 4.75 years (3.0
      10.33) for primary/primary-plus groups and 7.83 (5.4-11) in the secondary group.
      The mean (interquartile range) proportion of life lived with dystonia, derived as
      dystonia duration normalised to age was 0.68 (0.31-0.96); 0.59 (0.35-0.8); 0.75
      (0.62-0.95)and 0.9 (0.92-0.99) for primary, primary-plus, heredodegenerative and
      secondary-static dystonias respectively. Only 91/279 (32.6%) experienced a period
      of normal motor development. Carers perceived dystonia deterioration in 168/279
      (60.2%), stabilisation in 88/279 (31.5%) and improvement in 23/279 (8.2%).
      Dystonia occurred in 26/225 (11.6%) siblings: 14/26 secondary and 5/26
      heredodegenerative dystonia. Comorbidities were identified in 176/279 (63.1%)
      cases. Gross Motor Function Classification System (GMFCS) levels I-III were
      commoner in primary/primary-plus (37/49: 75%) compared with secondary/CP
      (29/230:13%) cases, chi(2) p<0.0001). DISCUSSION: In this selective cohort,
      childhood dystonia is severe, presenting early before worsening without
      remission. Secondary dystonias spend a higher proportion of life living with
      dystonia and lower functional capacity. Despite referral bias, services offering
      neurosurgical interventions and health service planning agencies should
      understand the context and predicament of life with childhood dystonia.

PMID- 24591459
TI  - L90m package to improve dementia care is announced in England.

PMID- 24591460
TI  - Ionic liquid gel-assisted electrodes for long-term cutaneous recordings.
AB  - The integration of an ionic liquid gel on conformal electrodes is investigated
      for applications in long-term cutaneous recordings. Electrodes made of Au and the
      conducting polymer PEDOT:PSS coated with the gel show a low impedance in contact
      with the skin that maintains a steady value over several days, paving the way for
      non-invasive, long-term monitoring of human electrophysiological activity. 

PMID- 24591461
TI  - Ir(III)-catalyzed C7-position-selective oxidative C-H alkenylation of indolines
      with alkenes in air.
AB  - An efficient method for C7-position-selective alkenylation of N-substituted
      indolines with alkenes is reported. Various 7-alkenylindolines were obtained in
      moderate to excellent yields in air in the presence of catalytic amounts of
      [Cp*IrCl2]2, AgOTf, and Cu(OAc)2. The protocol relies on the use of a carbonyl or
      carbamoyl group on the nitrogen atom of indoline as a directing group and is
      potentially applicable to the synthesis of 7-alkenylindoles and 7-alkylindoles.

PMID- 24591462
TI  - US trends in rates of arthroplasty for inflammatory arthritis including
      rheumatoid arthritis, juvenile idiopathic arthritis, and spondyloarthritis.
AB  - OBJECTIVE: Although rates of arthroplasty have increased dramatically, rates
      among patients with rheumatoid arthritis (RA) are reported to be decreasing. It
      is not known if this is also the case among patients with other inflammatory
      arthritides. This study was undertaken to evaluate rates of arthroplasty due to
      RA, juvenile idiopathic arthritis (JIA), spondyloarthritis (SpA), and a composite
      group of patients with inflammatory arthritides (IA), compared to arthroplasty
      rates among patients without inflammatory or autoimmune conditions. METHODS:
      Administrative discharge databases (State Inpatient Databases of the Healthcare
      Cost and Utilization Project, New York Department of Health Statewide Planning
      and Research Cooperative System, California Statewide Health Planning and
      Development) were used to compare rates of knee, hip, and shoulder arthroplasty
      occurring from 1991 to 2005. RESULTS: Of 2,839,325 arthroplasties in 1991-2005,
      2.7% were performed in patients with IA. The rate of arthroplasty for
      noninflammatory conditions doubled (124.5 per 100,000 persons in 1991 versus
      247.5 per 100,000 persons in 2005), while the rate for IA remained stable at 5.1
      per 100,000. Rates of arthroplasty for RA decreased slightly (4.6 per 100,000
      versus 4.5 per 100,000) and those for JIA decreased by nearly 50% (0.22 per
      100,000 versus 0.13 per 100,000), but the rate of arthroplasty for SpA increased
      by nearly 50% (0.22 per 100,000 versus 0.31 per 100,000). Age at the time of
      arthroplasty increased for patients with RA (mean +/- SD 63.4 +/- 12.7 years
      versus 64.9 +/- 12.8 years), JIA (30.9 +/- 12.2 years versus 36.7 +/- 14.9
      years), and SpA (54.3 +/- 16.1 years versus 60.4 +/- 13.9 years). However, the
      mean age at the time of arthroplasty among non-IA cases decreased (71.5 +/- 11.8
      years versus 69.0 +/- 12.0 years). CONCLUSION: This population-based study is the
      first to show that arthroplasty rates have decreased significantly among patients
      with JIA and minimally among patients with RA, and have increased among patients
      with SpA. The increased age at the time of arthroplasty among patients with JIA
      and SpA suggests that these patients are increasingly able to defer surgical
      interventions. Further research is needed to assess the ongoing effect of
      biologic agents on the need for arthroplasties in patients with IA.

PMID- 24591463
TI  - Diels-Alder/oxidative aromatization approach towards the all-carbon DEF tricyclic
      skeleton of daphenylline.
AB  - Daphenylline is a recently isolated Daphniphyllum alkaloid with an unprecedented
      novel hexacyclic scaffold. In this study, the synthesis of the fused all-carbon
      DEF tricyclic skeleton of daphenylline has been accomplished. Key steps of the
      reported sequence involve Evans asymmetric allylation, aldol condensation, Diels
      Alder reaction, and oxidative aromatization reactions. The developed strategy
      might lead to the total synthesis of daphenylline. 

PMID- 24591464
TI  - US drug regulator rejects accusations that it unfairly targets Indian generic
      firms.

PMID- 24591465
TI  - New practice guidelines: constrained or enhanced by the evidence?

PMID- 24591466
TI  - Problems with myocardial infarction definitions (DECEMBER 2013).

PMID- 24591467
TI  - In reply.

PMID- 24591468
TI  - Myasthenia gravis (NOVEMBER 2013).

PMID- 24591469
TI  - In reply.

PMID- 24591470
TI  - Q: Is hemoglobin A1c an accurate measure of glycemic control in all diabetic
      patients?

PMID- 24591471
TI  - Hepatitis C virus: here comes all-oral treatment.
AB  - Treatment for chronic hepatitis C virus (HCV) infection is evolving rapidly. The
      approval in 2013 of two new direct-acting antivirals-sofosbuvir (a polymerase
      inhibitor) and simeprevir (a second-generation protease inhibitor)-opens the door
      for an all-oral regimen, potentially avoiding interferon and its harsh side
      effects. Other direct-acting antivirals are under development. 

PMID- 24591472
TI  - When are effective medications just too expensive?

PMID- 24591473
TI  - New hypertension guidelines: one size fits most?
AB  - The report of the panel appointed to the eighth Joint National Committee on
      Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 8)
      is more evidence-based and focused than its predecessors, outlining a management
      strategy that is simpler and, in some instances, less aggressive. It has both
      strengths and weaknesses. 

PMID- 24591474
TI  - Prevention and treatment of influenza in the primary care office.
AB  - Influenza, a common respiratory infection, is a source of significant rates of
      illness, death, and loss of productivity. Annual vaccination is safe and
      effective in preventing disease and in reducing its severity. Yet a majority of
      eligible US adults do not receive the annual vaccine, at least in part because of
      misunderstandings about adverse reactions and clinical effectiveness. 

PMID- 24591476
TI  - Investigating an incidental finding of lymphopenia.

PMID- 24591475
TI  - A comparison of the malignancy incidence among patients with psoriatic arthritis
      and patients with rheumatoid arthritis in a large US cohort.
AB  - OBJECTIVE: To compare the incidence rates of malignancy among patients with
      psoriatic arthritis (PsA) and patients with rheumatoid arthritis (RA) in the
      Consortium of Rheumatology Researchers of North America (CORRONA) registry.
      METHODS: We analyzed 2,970 patients with PsA (7,133 patient-years of followup)
      and 19,260 patients with RA (53,864 patient-years of followup). Using a
      standardized adjudication process, we identified 40 confirmed malignancies in the
      patients with PsA and 307 confirmed malignancies in those with RA. Incidence
      rates were calculated per 100 patient-years. Incidence rate ratios were
      estimated, with adjustment for age, sex, disease duration, body mass index,
      disease activity, year of enrollment, and medication use. RESULTS: The overall
      malignancy incidence per 100 patient-years was similar between patients with PsA
      and patients with RA (0.56 [95% confidence interval (95% CI) 0.40-0.76] and 0.56
      [95% CI 0.50-0.63], respectively). Nonmelanoma skin cancer was the most common
      type of cancer in the overall cohort, with an incidence rate of 0.21 (95% CI 0.12
      0.35) in PsA, and 0.20 (95% CI 0.17-0.24) in RA, with a calculated incidence rate
      ratio of 1.05 (95% CI 0.61-1.80; P = 0.85). Lymphoma rates were similar in PsA
      and RA (0.04 [95% CI 0.01-0.12] and 0.04 [95% CI 0.02-0.06], respectively;
      incidence rate ratio 1.00 [95% CI 0.17-3.11]; P = 0.67). The adjusted incidence
      rate ratio of malignancy in PsA versus RA was 1.17 (95% CI 0.82-1.69; P = 0.37).
      CONCLUSION: The incidence rates across malignancy subtypes were similar in the
      PsA and RA cohorts from a US registry.

PMID- 24591477
TI  - Prediction of pulmonary complications and long-term survival in systemic
      sclerosis.
AB  - OBJECTIVE: To assess survival and incidence of organ-based complications in a
      large single-center cohort of unselected systemic sclerosis (SSc) patients, and
      to explore predictors of survival and clinically significant pulmonary fibrosis
      (PF) and pulmonary hypertension (PH). METHODS: The study cohort consisted of 398
      consecutive SSc patients, followed up for up to 15 years. Cox proportional
      hazards analysis with demographic, clinical, and laboratory characteristics as
      predictor variables was used to develop prediction models for pulmonary
      complications and survival. RESULTS: The overall survival estimate at the end of
      followup was 57% among patients with limited cutaneous SSc (lcSSc) and 50% among
      patients with diffuse cutaneous SSc (dcSSc) (P = 0.017). We found that greater
      age at disease onset, dcSSc, lower diffusing capacity for carbon monoxide (DLco),
      lower hemoglobin levels, higher serum creatinine levels, and the presence of PH
      or cardiac involvement were independent predictors of worse survival. Over the
      entire followup period, 42% of dcSSc patients and 22% of lcSSc patients developed
      clinically significant PF (P < 0.001). The variables that predicted clinically
      significant PF development were dcSSc, greater age at onset, lower forced vital
      capacity and DLco, and the presence of anti-topoisomerase I antibody, while the
      presence of anticentromere antibody was protective. There was no difference in
      cumulative incidence of PH between the 2 subsets-24% in lcSSc and 18% in dcSSc (P
      = 0.558). Incidence rates were 1-2% per year. The PH prediction model
      demonstrated that greater age at onset, increase in serum creatinine levels,
      lower DLco, and the presence of anti-RNA polymerase III or anti-U3 RNP antibodies
      were associated with increased risk of PH, while anti-topoisomerase I antibody
      positivity reduced the hazard. CONCLUSION: Our study provides data on long-term
      outcome of SSc and the timing and frequency of major organ complications. The
      predictive models we present could be used as clinical tools for patient risk
      stratification and could facilitate cohort enrichment for event-driven studies.

PMID- 24591478
TI  - Origin of porcine circovirus type 2 (PCV2) from swine affected by PCV2-associated
      diseases in Croatia.
AB  - Porcine circovirus type 2 (PCV2) causes some of the most significant economic
      losses in pig production. Several multisystemic syndromes have been attributed to
      PCV2 infection, which are known as PCV2-associated diseases (PCVDs). This study
      investigated the origin and evolution of PCV2 sequences in domestic pigs and wild
      boars affected by PCVDs in Croatia. Viral sequences were recovered from three
      wild boars diagnosed with PCV2-systemic disease (PCV2-SD), 63 fetuses positive
      for PCV2 DNA as determined by PCR, 14 domestic pigs affected with PCV2-SD
      (displaying severe interstitial nephritis) and five domestic pigs with
      proliferative and necrotising pneumonia. Seventeen complete PCV2 genomes were
      recovered. Phylogenetic and evolutionary analyses based on median-joining
      phylogenetic networks, amino acid alignments and principal coordinate analysis
      were performed using complete genomes, as well as complete and partial ORF
      sequences for ORF1 and ORF2. Two of the 17 PCV2 sequences belonged to PCV2a, 14
      to PCV2b and one was unclustered. PCV2b was the predominant genotype in Croatia
      and has been linked to international trade as a route of introduction.
      Correlation between particular viral strains with PCVDs is lacking. 

PMID- 24591479
TI  - Development of a low-dose fast-dissolving tablet formulation of Newcastle disease
      vaccine for low-cost backyard poultry immunisation.
AB  - The immunisation of backyard poultry is critical for maintaining healthy flocks
      to provide nutrition and income for low-resource farmers worldwide. A vaccine
      presentation for flocks of less than 50 birds could make it more affordable and
      accessible, increasing uptake and impact. Fast-dissolving tablets (FDT) of
      Newcastle disease virus (NDV) vaccine were produced by freeze drying the LaSota
      NDV strain combined with excipients into tablets containing a small number of
      doses and packaged in polymer blister sheets. The NDV-FDT vaccine maintained
      virus stability for more than six months at 4 degrees C, based on plaque assay
      and egg infectivity dose data. Stability was further confirmed in a challenge
      study, where the tablet vaccine elicited a strong immune response and provided
      100 per cent protection to vaccinated chickens infected with a virulent strain of
      NDV. The vaccine tablet can be diluted in water (no needle or syringe required)
      and administered either in drinking water or with a dropper via an intraocular
      and/or intransal route. Results indicate that FDTs containing a small number of
      doses are a feasible presentation for backyard poultry farmers. The compact
      packaging of the FDTs will also provide cost savings in storing and distributing
      the vaccine in the cold chain. 

PMID- 24591480
TI  - Limited interlaboratory comparison of Schmallenberg virus antibody detection in
      serum samples.
AB  - Eight veterinary institutes in seven different countries in Europe participated
      in a limited interlaboratory comparison trial to evaluate laboratory performances
      of Schmallenberg virus (SBV) antibody detection in serum. Seven different sheep
      sera and three different cattle sera were circulated, and all participating
      institutes were asked to test these sera using SBV antibody detection assay(s) in
      place in their laboratories. All laboratories within the trial performed a virus
      neutralisation test (VNT) as well as one or two ELISAs on all samples, and
      swiftly detected SBV antibodies using these assays. VNT was more sensitive in
      detecting SBV antibodies than several of the used ELISA assays. Based on the test
      results, one cattle and one sheep SBV antibody-positive serum were selected to
      serve as reference sera, which now can be supplied to other laboratories on
      request. 

PMID- 24591482
TI  - From the bedside to the bench and back again, with corneal confocal microscopy.

PMID- 24591481
TI  - Palmitate has proapoptotic and proinflammatory effects on articular cartilage and
      synergizes with interleukin-1.
AB  - OBJECTIVE: Obesity is a major risk factor for the development of osteoarthritis
      (OA) that is associated with a state of low-grade inflammation and increased
      circulating levels of adipokines and free fatty acids (FFAs). The aim of this
      study was to analyze the effects of saturated (palmitate) and monounsaturated
      (oleate) FFAs on articular chondrocytes, synoviocytes, and cartilage. METHODS:
      Human articular chondrocytes and fibroblast-like synoviocytes obtained from young
      healthy donors and OA chondrocytes from patients undergoing total knee
      replacement surgery were treated with palmitate or oleate alone or in combination
      with interleukin-1beta (IL-1beta). Cell viability, caspase activation, and gene
      expression of proinflammatory factors, extracellular matrix (ECM) proteins, and
      proteases were studied. In addition, chondrocyte viability, IL-6 production, and
      matrix damage were assessed in bovine and human articular cartilage explants
      cultured with FFAs in the presence or absence of IL-1beta. RESULTS: Palmitate,
      but not oleate, induced caspase activation and cell death in IL-1beta-stimulated
      normal chondrocytes, and up-regulated the expression of IL-6 and cyclooxygenase 2
      in chondrocytes and fibroblast-like synoviocytes through Toll-like receptor 4
      (TLR-4) signaling. In cartilage explants, palmitate induced chondrocyte death, IL
      6 release, and ECM degradation. Palmitate synergized with IL-1beta in stimulating
      proapoptotic and proinflammatory cellular responses. Pharmacologic inhibition of
      caspases or TLR-4 signaling reduced palmitate and IL-1beta induced cartilage
      damage. CONCLUSION: Palmitate acts as a proinflammatory and catabolic factor
      that, in synergy with IL-1beta, induces chondrocyte apoptosis and articular
      cartilage breakdown. Collectively, our data suggest that elevated levels of
      saturated FFAs that are often found in patients who are obese may contribute to
      the pathogenesis of OA.

PMID- 24591483
TI  - Measurement of fine-needle aspiration thyroglobulin levels increases the
      detection of metastatic papillary thyroid carcinoma in cystic neck lesions.
AB  - BACKGROUND: Patients with previously resected papillary thyroid carcinoma (PTC)
      are monitored for disease recurrence/metastasis by ultrasound surveillance and
      fine-needle aspiration (FNA) cytology. However, accurate diagnosis in lesions
      with cystic degeneration may be difficult due to scant cellularity. In the
      current study, the authors evaluated thyroglobulin in FNA (Tg-FNA) for detecting
      metastatic and/or recurrent PTC in patients with cystic neck lesions after
      thyroidectomy. METHODS: The pathology records were retrospectively searched for
      patients with previously resected PTC and subsequent Tg-FNA on a cystic neck
      mass. Tg-FNA was measured in needle rinses using a Tg assay. The ultrasound
      findings, Tg-FNA concentrations, and cytological and follow-up histological
      diagnoses were correlated. RESULTS: A total of 21 FNA specimens of cystic lesions
      from 19 patients were identified. Of 7 cases with cytologic and subsequent
      histologic diagnoses of metastatic PTC, the median Tg-FNA level was 100,982
      ng/mL. Of 8 cytologically benign cases, 7 cases had Tg-FNA levels < 0.2 ng/mL,
      and 1 aberrant case demonstrated elevated Tg-FNA of > 1000 ng/mL. For 6
      cytologically equivocal cases, including 3 classified as atypical/suspicious for
      carcinoma, 2 classified as insufficient/acellular debris, and 1 classified as
      spindle cell neoplasm, 4 patients demonstrated markedly elevated Tg-FNA levels (>
      150 ng/mL) with subsequent surgical confirmation of metastatic PTC, whereas 2
      patients had Tg-FNA levels of < 0.2 ng/mL with negative follow-up. Using a cutoff
      value of 0.2 ng/mL, Tg-FNA demonstrated a sensitivity of 100% and specificity of
      87.5%. CONCLUSIONS: Tg-FNA is a useful ancillary test that improves the detection
      of cystic PTC metastases. Particularly in cytologically nondiagnostic cases, the
      measurement of Tg-FNA helps to distinguish benign from malignant cystic lesions.

PMID- 24591484
TI  - Anatomy integration blueprint: A fourth-year musculoskeletal anatomy elective
      model.
AB  - Current undergraduate medical school curricular trends focus on both vertical
      integration of clinical knowledge into the traditionally basic science-dedicated
      curricula and increasing basic science education in the clinical years. This
      latter type of integration is more difficult and less reported on than the
      former. Here, we present an outline of a course wherein the primary learning and
      teaching objective is to integrate basic science anatomy knowledge with clinical
      education. The course was developed through collaboration by a multi-specialist
      course development team (composed of both basic scientists and physicians) and
      was founded in current adult learning theories. The course was designed to be
      widely applicable to multiple future specialties, using current published reports
      regarding the topics and clinical care areas relying heavily on anatomical
      knowledge regardless of specialist focus. To this end, the course focuses on the
      role of anatomy in the diagnosis and treatment of frequently encountered
      musculoskeletal conditions. Our iterative implementation and action research
      approach to this course development has yielded a curricular template for anatomy
      integration into clinical years. Key components for successful implementation of
      these types of courses, including content topic sequence, the faculty development
      team, learning approaches, and hidden curricula, were developed. We also report
      preliminary feedback from course stakeholders and lessons learned through the
      process. The purpose of this report is to enhance the current literature
      regarding basic science integration in the clinical years of medical school.

PMID- 24591485
TI  - Anatomical knowledge retention in third-year medical students prior to obstetrics
      and gynecology and surgery rotations.
AB  - Surgical anatomy is taught early in medical school training. The literature shows
      that many physicians, especially surgical specialists, think that anatomical
      knowledge of medical students is inadequate and nesting of anatomical sciences
      later in the clinical curriculum may be necessary. Quantitative data concerning
      this perception of an anatomical knowledge deficit are lacking, as are specifics
      as to what content should be reinforced. This study identifies baseline areas of
      strength and weakness in the surgical anatomy knowledge of medical students
      entering surgical rotations. Third-year medical students completed a 20-25
      question test at the beginning of the General Surgery and Obstetrics and
      Gynecology rotations. Knowledge of inguinal anatomy (45.3%), orientation in
      abdominal cavity (38.8%), colon (27.7%), and esophageal varices (12.8%) was poor.
      The numbers in parentheses are the percentage of questions answered correctly per
      topic. In comparing those scores to matched test items from this cohort as first
      year students in the anatomy course, the drop in retention overall was very
      significant (P = 0.009) from 86.9 to 51.5%. Students also scored lower in
      questions relating to pelvic organs (46.7%), urogenital development (54.0%),
      pulmonary development (17.8%), and pregnancy (17.8%). These data showed that
      indeed, knowledge of surgical anatomy is poor for medical students entering
      surgical clerkships. These data collected will be utilized to create interactive
      learning modules, aimed at improving clinically relevant anatomical knowledge
      retention. These modules, which will be available to students during their
      inpatient surgical rotations, connect basic anatomy principles to clinical cases,
      with the ultimate goal of closing the anatomical knowledge gap.

PMID- 24591486
TI  - PET/CT with sodium 18F-fluoride for management of patients with prostate cancer.

PMID- 24591487
TI  - The lumped constant for the galactose analog 2-18F-fluoro-2-deoxy-D-galactose is
      increased in patients with parenchymal liver disease.
AB  - The galactose analog 2-(18)F-fluoro-2-deoxy-d-galactose ((18)F-FDGal) is a
      suitable PET tracer for measuring hepatic galactokinase capacity in vivo, which
      provides estimates of hepatic metabolic function. As a result of a higher
      affinity of galactokinase toward galactose, the lumped constant (LC) for (18)F
      FDGal was 0.13 in healthy subjects. The aim of the present study was to test the
      hypothesis of a significantly different LC for (18)F-FDGal in patients with
      parenchymal liver disease. METHODS: Nine patients with liver cirrhosis were
      studied in connection with a previous study with determination of hepatic
      intrinsic clearance of 18F-FDGal (V*(max/K*(m)). The present study determined the
      hepatic removal kinetics of galactose, including hepatic intrinsic clearance of
      galactose (V(max)/K(m)) from measurements of hepatic blood flow and arterial and
      liver vein blood galactose concentrations at increasing galactose infusions. LC
      for 18F-FDGal was calculated as (V*(max)/K*(m))/(V(max)/K(m)). On a second day, a
      dynamic 18-FDGal PET study with simultaneous infusion of galactose (mean arterial
      galactose concentration, 6.1 mmol/L of blood) and blood samples from a radial
      artery was performed, with determination of hepatic systemic clearance of 18F
      FDGal (K*(+gal) from linear analysis of data (Gjedde-Patlak method). The maximum
      hepatic removal rate of galactose was estimated from 18F-FDGal PET data
      (V(max)(PET)) using the estimated LC. RESULTS: The mean hepatic V(max) of
      galactose was 1.18 mmol/min, the mean K(m) was 0.91 mmol/L of blood and the mean
      V(max)/K(m) was 1.18 L of blood/min. When compared with values of healthy
      subjects, K(m) did not differ (P = 0.77), whereas both V(max) and V(max)/K(m)
      were significantly lower in patients (both P < 0.01). Mean LC for 18LF-FDGal was
      0.24, which was significantly higher than the mean LC of 0.13 in healthy subjects
      (P < 0.0001). Mean K*(+gal) determined from the PET study was 0.019 L of
      blood/min/L of liver tissue, which was not significantly different from that in
      healthy subjects (P = 0.85). Mean hepatic V(max)(PET) was 0.57 mmol/min/L of
      liver tissue, which was significantly lower than the value in healthy subjects
      (1.41 mmol/min/L of liver tissue (P < 0.0001). CONCLUSION: Disease may change the
      LC for a pet tracer, and this study demonstrated the importance of using the
      correct LC.

PMID- 24591488
TI  - Radionuclides in nephrourology, Part 2: pitfalls and diagnostic applications.
AB  - Radionuclide renal scintigraphy provides important functional data to assist in
      the diagnosis and management of patients with a variety of suspected
      genitourinary tract problems, but the procedures are underutilized. Maximizing
      the utility of the available studies (as well as the perception of utility by
      referring physicians) requires a clear understanding of the clinical question,
      attention to quality control, acquisition of the essential elements necessary to
      produce an informed interpretation, and production of a report that presents a
      coherent impression based on data contained in the report and that specifically
      addresses the clinical question. To help achieve these goals, part 1 of this
      review addressed the available radiopharmaceuticals, quality control, and
      quantitative indices, including the measurement of absolute and relative renal
      function. Part 2 assumes familiarity with part 1 and focuses on the common
      clinical indications of suspected obstruction and renovascular hypertension; part
      2 also summarizes the status of radionuclide renal imaging in the evaluation of
      the transplanted kidney and the detection of infection, discusses potential
      pitfalls, and concludes with suggestions for future research. The series of SAM
      questions accompanying parts 1 and 2 has been designed to reinforce and extend
      points made in the review. Although the primary focus is the adult patient,
      aspects of the review also apply to the pediatric population. 

PMID- 24591489
TI  - PET/CT imaging of chemokine receptor CCR5 in vascular injury model using targeted
      nanoparticle.
AB  - Inflammation plays important roles at all stages of atherosclerosis. Chemokine
      systems have major effects on the initiation and progression of atherosclerosis
      by controlling the trafficking of inflammatory cells in vivo through interaction
      with their receptors. Chemokine receptor 5 (CCR5) has been reported to be an
      active participant in the late stage of atherosclerosis and has the potential as
      a prognostic biomarker for plaque stability. However, its diagnostic potential
      has not yet been explored. The purpose of this study was to develop a targeted
      nanoparticle for sensitive and specific PET/CT imaging of the CCR5 receptor in an
      apolipoprotein E knock-out (ApoE(-/-)) mouse vascular injury model. METHODS: The
      D-Ala1-peptide T-amide (DAPTA) peptide was selected as a targeting ligand for the
      CCR5 receptor. Through controlled conjugation and polymerization, a biocompatible
      poly(methyl methacrylate)-core/polyethylene glycol-shell amphiphilic comblike
      nanoparticle was prepared and labeled with (64)Cu for CCR5 imaging in the ApoE(-/
      ) wire-injury model. Immunohistochemistry, histology, and real-time reverse
      transcription polymerase chain reaction (RT-PCR) were performed to assess the
      disease progression and upregulation of CCR5 receptor. RESULTS: The (64)Cu-DOTA
      DAPTA tracer showed specific PET imaging of CCR5 in the ApoE(-/-) mice. The
      targeted (64)Cu-DOTA-DAPTA-comb nanoparticles showed extended blood signal and
      optimized biodistribution. The tracer uptake analysis showed significantly higher
      accumulations at the injury lesions than those acquired from the sham-operated
      sites. The competitive PET receptor blocking studies confirmed the CCR5 receptor
      specific uptake. The assessment of (64)Cu-DOTA-DAPTA-comb in C57BL/6 mice and
      (64)Cu-DOTA-comb in ApoE(-/-) mice verified low nonspecific nanoparticle uptake.
      Histology, immunohistochemistry, and RT-PCR analyses verified the upregulation of
      CCR5 in the progressive atherosclerosis model. CONCLUSION: This work provides a
      nanoplatform for sensitive and specific detection of CCR5's physiologic functions
      in an animal atherosclerosis model.

PMID- 24591492
TI  - Screening for HCV.

PMID- 24591490
TI  - Integrative approaches for modeling regulation and function of the respiratory
      system.
AB  - Mathematical models have been central to understanding the interaction between
      neural control and breathing. Models of the entire respiratory system-which
      comprises the lungs and the neural circuitry that controls their ventilation-have
      been derived using simplifying assumptions to compartmentalize each component of
      the system and to define the interactions between components. These full system
      models often rely-through necessity-on empirically derived relationships or
      parameters, in addition to physiological values. In parallel with the development
      of whole respiratory system models are mathematical models that focus on
      furthering a detailed understanding of the neural control network, or of the
      several functions that contribute to gas exchange within the lung. These models
      are biophysically based, and rely on physiological parameters. They include
      single-unit models for a breathing lung or neural circuit, through to spatially
      distributed models of ventilation and perfusion, or multicircuit models for
      neural control. The challenge is to bring together these more recent advances in
      models of neural control with models of lung function, into a full simulation for
      the respiratory system that builds upon the more detailed models but remains
      computationally tractable. This requires first understanding the mathematical
      models that have been developed for the respiratory system at different levels,
      and which could be used to study how physiological levels of O2 and CO2 in the
      blood are maintained.

PMID- 24591493
TI  - Screening for HCV.

PMID- 24591494
TI  - Rapid growth forecast for digital health sector.

PMID- 24591495
TI  - Vision and change through the genome consortium for active teaching using next
      generation sequencing (GCAT-SEEK).

PMID- 24591496
TI  - Re: misconceptions are "so yesterday!".

PMID- 24591497
TI  - Considering the role of affect in learning: monitoring students' self-efficacy,
      sense of belonging, and science identity.

PMID- 24591498
TI  - Vision and change in the biology community: snapshots of change.

PMID- 24591499
TI  - Engaging with molecular form to understand function.

PMID- 24591500
TI  - Recent research in science teaching and learning.

PMID- 24591501
TI  - Assessment of course-based undergraduate research experiences: a meeting report.
AB  - The Course-Based Undergraduate Research Experiences Network (CUREnet) was
      initiated in 2012 with funding from the National Science Foundation program for
      Research Coordination Networks in Undergraduate Biology Education. CUREnet aims
      to address topics, problems, and opportunities inherent to integrating research
      experiences into undergraduate courses. During CUREnet meetings and discussions,
      it became apparent that there is need for a clear definition of what constitutes
      a CURE and systematic exploration of what makes CUREs meaningful in terms of
      student learning. Thus, we assembled a small working group of people with
      expertise in CURE instruction and assessment to: 1) draft an operational
      definition of a CURE, with the aim of defining what makes a laboratory course or
      project a "research experience"; 2) summarize research on CUREs, as well as
      findings from studies of undergraduate research internships that would be useful
      for thinking about how students are influenced by participating in CUREs; and 3)
      identify areas of greatest need with respect to CURE assessment, and directions
      for future research on and evaluation of CUREs. This report summarizes the
      outcomes and recommendations of this meeting. 

PMID- 24591502
TI  - Is it the intervention or the students? using linear regression to control for
      student characteristics in undergraduate STEM education research.
AB  - Although researchers in undergraduate science, technology, engineering, and
      mathematics education are currently using several methods to analyze learning
      gains from pre- and posttest data, the most commonly used approaches have
      significant shortcomings. Chief among these is the inability to distinguish
      whether differences in learning gains are due to the effect of an instructional
      intervention or to differences in student characteristics when students cannot be
      assigned to control and treatment groups at random. Using pre- and posttest
      scores from an introductory biology course, we illustrate how the methods
      currently in wide use can lead to erroneous conclusions, and how multiple linear
      regression offers an effective framework for distinguishing the impact of an
      instructional intervention from the impact of student characteristics on test
      score gains. In general, we recommend that researchers always use student-level
      regression models that control for possible differences in student ability and
      preparation to estimate the effect of any nonrandomized instructional
      intervention on student performance. 

PMID- 24591503
TI  - Putting PhDs to work: career planning for today's scientist.
AB  - Individual development plans (IDPs) have been promoted nationally as a tool to
      help research trainees explore career opportunities and set career goals. Despite
      the interest in IDPs from a policy perspective, there is little information about
      how they have been used. The authors examined IDP awareness and use, the benefits
      of creating an IDP, and ways to facilitate its use by administering a survey to
      current or former postdoctoral researchers via the National Postdoctoral
      Association (NPA) and University of Alabama at Birmingham email lists;
      individuals belonging to Federation of American Societies for Experimental
      Biology member societies who mentored postdocs; and postdoctoral administrators
      at member institutions of the Association of American Medical Colleges and the
      NPA. Although most postdoctoral administrators (>80%) were familiar with IDPs,
      less than 50% of postdocs and only 20% of mentors were aware of IDPs. For those
      postdocs and mentors who reported creating an IDP, the process helped postdocs to
      identify the skills and abilities necessary for career success and facilitated
      communication between postdocs and their mentors. Despite the fact that creating
      an IDP benefits postdocs and mentors, IDP use will likely remain low unless
      institutions and research mentors encourage trainees to engage in this process. 

PMID- 24591504
TI  - Integrating quantitative thinking into an introductory biology course improves
      students' mathematical reasoning in biological contexts.
AB  - Recent calls for improving undergraduate biology education have emphasized the
      importance of students learning to apply quantitative skills to biological
      problems. Motivated by students' apparent inability to transfer their existing
      quantitative skills to biological contexts, we designed and taught an
      introductory molecular and cell biology course in which we integrated application
      of prerequisite mathematical skills with biology content and reasoning throughout
      all aspects of the course. In this paper, we describe the principles of our
      course design and present illustrative examples of course materials integrating
      mathematics and biology. We also designed an outcome assessment made up of items
      testing students' understanding of biology concepts and their ability to apply
      mathematical skills in biological contexts and administered it as a
      pre/postcourse test to students in the experimental section and other sections of
      the same course. Precourse results confirmed students' inability to spontaneously
      transfer their prerequisite mathematics skills to biological problems.
      Pre/postcourse outcome assessment comparisons showed that, compared with students
      in other sections, students in the experimental section made greater gains on
      integrated math/biology items. They also made comparable gains on biology items,
      indicating that integrating quantitative skills into an introductory biology
      course does not have a deleterious effect on students' biology learning. 

PMID- 24591505
TI  - The genetic drift inventory: a tool for measuring what advanced undergraduates
      have mastered about genetic drift.
AB  - Understanding genetic drift is crucial for a comprehensive understanding of
      biology, yet it is difficult to learn because it combines the conceptual
      challenges of both evolution and randomness. To help assess strategies for
      teaching genetic drift, we have developed and evaluated the Genetic Drift
      Inventory (GeDI), a concept inventory that measures upper-division students'
      understanding of this concept. We used an iterative approach that included
      extensive interviews and field tests involving 1723 students across five
      different undergraduate campuses. The GeDI consists of 22 agree-disagree
      statements that assess four key concepts and six misconceptions. Student scores
      ranged from 4/22 to 22/22. Statements ranged in mean difficulty from 0.29 to 0.80
      and in discrimination from 0.09 to 0.46. The internal consistency, as measured
      with Cronbach's alpha, ranged from 0.58 to 0.88 across five iterations. Test
      retest analysis resulted in a coefficient of stability of 0.82. The true-false
      format means that the GeDI can test how well students grasp key concepts central
      to understanding genetic drift, while simultaneously testing for the presence of
      misconceptions that indicate an incomplete understanding of genetic drift. The
      insights gained from this testing will, over time, allow us to improve
      instruction about this key component of evolution. 

PMID- 24591506
TI  - Development and effectiveness of an educational card game as supplementary
      material in understanding selected topics in biology.
AB  - The complex concepts and vocabulary of biology classes discourage many students.
      In this study, a pretest-posttest model was used to test the effectiveness of an
      educational card game in reinforcing biological concepts in comparison with
      traditional teaching methods. The subjects of this study were two biology classes
      at Bulacan State University-Sarmiento Campus. Both classes received conventional
      instruction; however, the experimental group's instruction was supplemented with
      the card game, while the control group's instruction was reinforced with
      traditional exercises and assignments. The score increases from pretest to
      posttest showed that both methods effectively reinforced biological concepts, but
      a t test showed that the card game is more effective than traditional teaching
      methods. Additionally, students from the experimental group evaluated the card
      game using five criteria: goals, design, organization, playability, and
      usefulness. The students rated the material very satisfactory. 

PMID- 24591507
TI  - Online plagiarism training falls short in biology classrooms.
AB  - Online plagiarism tutorials are increasingly popular in higher education, as
      faculty and staff try to curb the plagiarism epidemic. Yet no research has
      validated the efficacy of such tools in minimizing plagiarism in the sciences.
      Our study compared three plagiarism-avoidance training regimens (i.e., no
      training, online tutorial, or homework assignment) and their impacts on students'
      ability to accurately discriminate plagiarism from text that is properly quoted,
      paraphrased, and attributed. Using pre- and postsurveys of 173 undergraduate
      students in three general ecology courses, we found that students given the
      homework assignment had far greater success in identifying plagiarism or the lack
      thereof compared with students given no training. In general, students trained
      with the homework assignment more successfully identified plagiarism than did
      students trained with the online tutorial. We also found that the summative
      assessment associated with the plagiarism-avoidance training formats (i.e.,
      homework grade and online tutorial assessment score) did not correlate with
      student improvement on surveys through time. 

PMID- 24591508
TI  - Guiding students to develop an understanding of scientific inquiry: a science
      skills approach to instruction and assessment.
AB  - New approaches for teaching and assessing scientific inquiry and practices are
      essential for guiding students to make the informed decisions required of an
      increasingly complex and global society. The Science Skills approach described
      here guides students to develop an understanding of the experimental skills
      required to perform a scientific investigation. An individual teacher's
      investigation of the strategies and tools she designed to promote scientific
      inquiry in her classroom is outlined. This teacher-driven action research in the
      high school biology classroom presents a simple study design that allowed for
      reciprocal testing of two simultaneous treatments, one that aimed to guide
      students to use vocabulary to identify and describe different scientific
      practices they were using in their investigations-for example, hypothesizing,
      data analysis, or use of controls-and another that focused on scientific
      collaboration. A knowledge integration (KI) rubric was designed to measure how
      students integrated their ideas about the skills and practices necessary for
      scientific inquiry. KI scores revealed that student understanding of scientific
      inquiry increased significantly after receiving instruction and using assessment
      tools aimed at promoting development of specific inquiry skills. General
      strategies for doing classroom-based action research in a straightforward and
      practical way are discussed, as are implications for teaching and evaluating
      introductory life sciences courses at the undergraduate level. 

PMID- 24591509
TI  - Redefining authentic research experiences in introductory biology laboratories
      and barriers to their implementation.
AB  - Incorporating authentic research experiences in introductory biology laboratory
      classes would greatly expand the number of students exposed to the excitement of
      discovery and the rigor of the scientific process. However, the essential
      components of an authentic research experience and the barriers to their
      implementation in laboratory classes are poorly defined. To guide future reform
      efforts in this area, we conducted a national survey of biology faculty members
      to determine 1) their definitions of authentic research experiences in laboratory
      classes, 2) the extent of authentic research experiences currently experienced in
      their laboratory classes, and 3) the barriers that prevent incorporation of
      authentic research experiences into these classes. Strikingly, the definitions of
      authentic research experiences differ among faculty members and tend to emphasize
      either the scientific process or the discovery of previously unknown data. The
      low level of authentic research experiences in introductory biology labs suggests
      that more development and support is needed to increase undergraduate exposure to
      research experiences. Faculty members did not cite several barriers commonly
      assumed to impair pedagogical reform; however, their responses suggest that
      expanded support for development of research experiences in laboratory classes
      could address the most common barrier. 

PMID- 24591511
TI  - Immediate dissemination of student discoveries to a model organism database
      enhances classroom-based research experiences.
AB  - Use of inquiry-based research modules in the classroom has soared over recent
      years, largely in response to national calls for teaching that provides
      experience with scientific processes and methodologies. To increase the
      visibility of in-class studies among interested researchers and to strengthen
      their impact on student learning, we have extended the typical model of inquiry
      based labs to include a means for targeted dissemination of student-generated
      discoveries. This initiative required: 1) creating a set of research-based lab
      activities with the potential to yield results that a particular scientific
      community would find useful and 2) developing a means for immediate sharing of
      student-generated results. Working toward these goals, we designed guides for
      course-based research aimed to fulfill the need for functional annotation of the
      Tetrahymena thermophila genome, and developed an interactive Web database that
      links directly to the official Tetrahymena Genome Database for immediate,
      targeted dissemination of student discoveries. This combination of research via
      the course modules and the opportunity for students to immediately "publish"
      their novel results on a Web database actively used by outside scientists
      culminated in a motivational tool that enhanced students' efforts to engage the
      scientific process and pursue additional research opportunities beyond the
      course. 

PMID- 24591512
TI  - Effect of time on perceived gains from an undergraduate research program.
AB  - The current study examines the trajectories of student perceived gains as a
      result of time spent in an undergraduate research experience (URE). Data for the
      study come from a survey administered at three points over a 1-yr period: before
      participation in the program, at the end of a Summer segment of research, and at
      the end of the year. Repeated-measures analysis of variance was used to examine
      the effect of time on perceived gains in student research skills, research
      confidence, and understanding of research processes. The results suggest that the
      students experienced different gains/benefits at developmentally different stages
      of their UREs. Participants reported gains in fewer areas at the end of the
      Summer segment compared with the end of the yearlong experience, thus supporting
      the notion that longer UREs offer students more benefit. 

PMID- 24591510
TI  - A course-based research experience: how benefits change with increased investment
      in instructional time.
AB  - There is widespread agreement that science, technology, engineering, and
      mathematics programs should provide undergraduates with research experience.
      Practical issues and limited resources, however, make this a challenge. We have
      developed a bioinformatics project that provides a course-based research
      experience for students at a diverse group of schools and offers the opportunity
      to tailor this experience to local curriculum and institution-specific student
      needs. We assessed both attitude and knowledge gains, looking for insights into
      how students respond given this wide range of curricular and institutional
      variables. While different approaches all appear to result in learning gains, we
      find that a significant investment of course time is required to enable students
      to show gains commensurate to a summer research experience. An alumni survey
      revealed that time spent on a research project is also a significant factor in
      the value former students assign to the experience one or more years later. We
      conclude: 1) implementation of a bioinformatics project within the biology
      curriculum provides a mechanism for successfully engaging large numbers of
      students in undergraduate research; 2) benefits to students are achievable at a
      wide variety of academic institutions; and 3) successful implementation of course
      based research experiences requires significant investment of instructional time
      for students to gain full benefit. 

PMID- 24591513
TI  - The project ownership survey: measuring differences in scientific inquiry
      experiences.
AB  - A growing body of research documents the positive outcomes of research
      experiences for undergraduates, including increased persistence in science. Study
      of undergraduate lab learning experiences has demonstrated that the design of the
      experience influences the extent to which students report ownership of the
      project and that project ownership is one of the psychosocial factors involved in
      student retention in the sciences. To date, methods for measuring project
      ownership have not been suitable for the collection of larger data sets. The
      current study aims to rectify this by developing, presenting, and evaluating a
      new instrument for measuring project ownership. Eighteen scaled items were
      generated based on prior research and theory related to project ownership and
      combined with 30 items shown to measure respondents' emotions about an
      experience, resulting in the Project Ownership survey (POS). The POS was analyzed
      to determine its dimensionality, reliability, and validity. The POS had a
      coefficient alpha of 0.92 and thus has high internal consistency. Known-groups
      validity was analyzed through the ability of the instrument to differentiate
      between students who studied in traditional versus research-based laboratory
      courses. The POS scales as differentiated between the groups and findings
      paralleled previous results in relation to the characteristics of project
      ownership. 

PMID- 24591514
TI  - Reinventing the case study for community health and primary care research.

PMID- 24591515
TI  - Adenovirus composition, proteolysis, and disassembly studied by in-depth
      qualitative and quantitative proteomics.
AB  - Using high-resolution MS-based proteomics in combination with multiple protease
      digestion, we profiled, with on average 90% sequence coverage, all 13 viral
      proteins present in an human adenovirus (HAdV) vector. This in-depth profile
      provided multiple peptide-based evidence on intrinsic protease activity affecting
      several HAdV proteins. Next, the generated peptide library was used to develop a
      targeted proteomics method using selected reaction monitoring (SRM) aimed at
      quantitative profiling of the stoichiometry of all 13 proteins present in the
      HAdV. We also used this method to probe the release of specific virus proteins
      initiated by thermal stimulation, mimicking the early stage of HAdV disassembly
      during entry into host cells. We confirmed the copy numbers of the most well
      characterized viral capsid components and established the copy numbers for
      proteins whose stoichiometry has so far not been accurately defined. We also
      found that heating HAdV induces the complete release of the penton base and fiber
      proteins as well as a substantial release of protein VIII and VI. For these
      latter proteins, maturational proteolysis by the adenoviral protease leads to the
      differential release of fragments with certain peptides being fully released and
      others largely retained in the AdV particles. This information is likely to be
      beneficial for the ongoing interpretation of high resolution cryoEM and x-ray
      electron density maps. 

PMID- 24591516
TI  - Long-chain acyl-CoA dehydrogenase deficiency as a cause of pulmonary surfactant
      dysfunction.
AB  - Long-chain acyl-CoA dehydrogenase (LCAD) is a mitochondrial fatty acid oxidation
      enzyme whose expression in humans is low or absent in organs known to utilize
      fatty acids for energy such as heart, muscle, and liver. This study demonstrates
      localization of LCAD to human alveolar type II pneumocytes, which synthesize and
      secrete pulmonary surfactant. The physiological role of LCAD and the fatty acid
      oxidation pathway in lung was subsequently studied using LCAD knock-out mice.
      Lung fatty acid oxidation was reduced in LCAD(-/-) mice. LCAD(-/-) mice
      demonstrated reduced pulmonary compliance, but histological examination of lung
      tissue revealed no obvious signs of inflammation or pathology. The changes in
      lung mechanics were found to be due to pulmonary surfactant dysfunction. Large
      aggregate surfactant isolated from LCAD(-/-) mouse lavage fluid had significantly
      reduced phospholipid content as well as alterations in the acyl chain composition
      of phosphatidylcholine and phosphatidylglycerol. LCAD(-/-) surfactant
      demonstrated functional abnormalities when subjected to dynamic compression
      expansion cycling on a constrained drop surfactometer. Serum albumin, which has
      been shown to degrade and inactivate pulmonary surfactant, was significantly
      increased in LCAD(-/-) lavage fluid, suggesting increased epithelial
      permeability. Finally, we identified two cases of sudden unexplained infant death
      where no lung LCAD antigen was detectable. Both infants were homozygous for an
      amino acid changing polymorphism (K333Q). These findings for the first time
      identify the fatty acid oxidation pathway and LCAD in particular as factors
      contributing to the pathophysiology of pulmonary disease. 

PMID- 24591518
TI  - The pre-endosymbiont hypothesis: a new perspective on the origin and evolution of
      mitochondria.
AB  - Mitochondrial DNA (mtDNA) is unquestionably the remnant of an alpha
      proteobacterial genome, yet only ~10%-20% of mitochondrial proteins are
      demonstrably alpha-proteobacterial in origin (the "alpha-proteobacterial
      component," or APC). The evolutionary ancestry of the non-alpha-proteobacterial
      component (NPC) is obscure and not adequately accounted for in current models of
      mitochondrial origin. I propose that in the host cell that accommodated an alpha
      proteobacterial endosymbiont, much of the NPC was already present, in the form of
      a membrane-bound metabolic organelle (the premitochondrion) that
      compartmentalized many of the non-energy-generating functions of the contemporary
      mitochondrion. I suggest that this organelle also possessed a protein import
      system and various ion and small-molecule transporters. In such a scenario, an
      alpha-proteobacterial endosymbiont could have been converted relatively directly
      and rapidly into an energy-generating organelle that incorporated the extant
      metabolic functions of the premitochondrion. This model (the "pre-endosymbiont
      hypothesis") effectively represents a synthesis of previous, contending
      mitochondrial origin hypotheses, with the bulk of the mitochondrial proteome
      (much of the NPC) having an endogenous origin and the minority component (the
      APC) having a xenogenous origin.

PMID- 24591517
TI  - Receptor tyrosine kinases: legacy of the first two decades.
AB  - Receptor tyrosine kinases (RTKs) and their cellular signaling pathways play
      important roles in normal development and homeostasis. Aberrations in their
      activation or signaling leads to many pathologies, especially cancers, motivating
      the development of a variety of drugs that block RTK signaling that have been
      successfully applied for the treatment of many cancers. As the current field of
      RTKs and their signaling pathways are covered by a very large amount of
      literature, spread over half a century, I am focusing the scope of this review on
      seminal discoveries made before tyrosine phosphorylation was discovered, and on
      the early days of research into RTKs and their cellular signaling pathways. I
      review the history of the early days of research in the field of RTKs. I
      emphasize key early findings, which provided conceptual frameworks for addressing
      the questions of how RTKs are activated and how they regulate intracellular
      signaling pathways. 

PMID- 24591519
TI  - Origins of eukaryotic sexual reproduction.
AB  - Sexual reproduction is a nearly universal feature of eukaryotic organisms. Given
      its ubiquity and shared core features, sex is thought to have arisen once in the
      last common ancestor to all eukaryotes. Using the perspectives of molecular
      genetics and cell biology, we consider documented and hypothetical scenarios for
      the instantiation and evolution of meiosis, fertilization, sex determination,
      uniparental inheritance of organelle genomes, and speciation. 

PMID- 24591520
TI  - Function and regulation of the endosomal fusion and fission machineries.
AB  - Organelles within the endomembrane system are connected via vesicle flux. Along
      the endocytic pathway, endosomes are among the most versatile organelles. They
      sort cargo through tubular protrusions for recycling or through intraluminal
      vesicles for degradation. Sorting involves numerous machineries, which mediate
      fission of endosomal transport intermediates and fusion with other endosomes or
      eventually with lysosomes. Here we review the recent advances in our
      understanding of these processes with a particular focus on the Rab GTPases,
      tethering factors, and retromer. The cytoskeleton has also been recently
      recognized as a central player in membrane dynamics of endosomes, and this review
      covers the regulation of the machineries that govern the formation of branched
      actin networks through the WASH and Arp2/3 complexes in relation with cargo
      recycling and endosomal fission. 

PMID- 24591521
TI  - Endocytosis and signaling during development.
AB  - The development of multicellular organisms relies on an intricate choreography of
      intercellular communication events that pattern the embryo and coordinate the
      formation of tissues and organs. It is therefore not surprising that
      developmental biology, especially using genetic model organisms, has contributed
      significantly to the discovery and functional dissection of the associated signal
      transduction cascades. At the same time, biophysical, biochemical, and cell
      biological approaches have provided us with insights into the underlying cell
      biological machinery. Here we focus on how endocytic trafficking of signaling
      components (e.g., ligands or receptors) controls the generation, propagation,
      modulation, reception, and interpretation of developmental signals. A
      comprehensive enumeration of the links between endocytosis and signal
      transduction would exceed the limits of this review. We will instead use examples
      from different developmental pathways to conceptually illustrate the various
      functions provided by endocytic processes during key steps of intercellular
      signaling. 

PMID- 24591522
TI  - Regulation of the X chromosomes in Caenorhabditis elegans.
AB  - Dosage compensation, which regulates the expression of genes residing on the sex
      chromosomes, has provided valuable insights into chromatin-based mechanisms of
      gene regulation. The nematode Caenorhabditis elegans has adopted various
      strategies to down-regulate and even nearly silence the X chromosomes. This
      article discusses the different chromatin-based strategies used in somatic
      tissues and in the germline to modulate gene expression from the C. elegans X
      chromosomes and compares these strategies to those used by other organisms to
      cope with similar X-chromosome dosage differences. 

PMID- 24591523
TI  - Neural Trade-Offs between Recognizing and Categorizing Own- and Other-Race Faces.
AB  - Behavioral research has suggested a trade-off relationship between individual
      recognition and race categorization of own- and other-race faces, which is an
      important behavioral marker of face processing expertise. However, little is
      known about the neural mechanisms underlying this trade-off. Using functional
      magnetic resonance imaging (fMRI) methodology, we concurrently asked participants
      to recognize and categorize own- and other-race faces to examine the neural
      correlates of this trade-off relationship. We found that for other-race faces,
      the fusiform face area (FFA) and occipital face area (OFA) responded more to
      recognition than categorization, whereas for own-race faces, the responses were
      equal for the 2 tasks. The right superior temporal sulcus (STS) responses were
      the opposite to those of the FFA and OFA. Further, recognition enhanced the
      functional connectivity from the right FFA to the right STS, whereas
      categorization enhanced the functional connectivity from the right OFA to the
      right STS. The modulatory effects of these 2 couplings were negatively
      correlated. Our findings suggested that within the core face processing network,
      although recognizing and categorizing own- and other-race faces activated the
      same neural substrates, there existed neural trade-offs whereby their activations
      and functional connectivities were modulated by face race type and task demand
      due to one's differential processing expertise with own- and other-race faces. 

PMID- 24591524
TI  - The Relative Influence of Goal and Kinematics on Corticospinal Excitability
      Depends on the Information Provided to the Observer.
AB  - Viewing a person perform an action activates the observer's motor system. Whether
      this phenomenon reflects the action's kinematics or its final goal remains a
      matter of debate. One alternative to this apparent controversy is that the
      relative influence of goal and kinematics depends on the information available to
      the observer. Here, we addressed this possibility. For this purpose, we measured
      corticospinal excitability (CSE) while subjects viewed 3 different grasping
      actions with 2 goals: a large and a small object. Actions were directed to the
      large object, the small object, or corrected online in which case the goal
      switched during the movement. We first determined the kinematics and dynamics of
      the 3 actions during execution. This information was used in 2 other experiments
      to measure CSE while observers viewed videos of the same actions. CSE was
      recorded prior to movement onset and at 3 time points during the observed action.
      To discern between goal and kinematics, information about the goal was
      manipulated across experiments. We found that the goal influenced CSE only when
      its identity was known before movement onset. In contrast, a kinematic modulation
      of CSE was observed whether or not information regarding the goal was provided. 

PMID- 24591525
TI  - Dynamic Development of Regional Cortical Thickness and Surface Area in Early
      Childhood.
AB  - Cortical thickness (CT) and surface area (SA) are altered in many
      neuropsychiatric disorders and are correlated with cognitive functioning. Little
      is known about how these components of cortical gray matter develop in the first
      years of life. We studied the longitudinal development of regional CT and SA
      expansion in healthy infants from birth to 2 years. CT and SA have distinct and
      heterogeneous patterns of development that are exceptionally dynamic; overall CT
      increases by an average of 36.1%, while cortical SA increases 114.6%. By age 2,
      CT is on average 97% of adult values, compared with SA, which is 69%. This
      suggests that early identification, prevention, and intervention strategies for
      neuropsychiatric illness need to be targeted to this period of rapid postnatal
      brain development, and that SA expansion is the principal driving factor in
      cortical volume after 2 years of age. 

PMID- 24591526
TI  - Anterior Cingulate Cortex Cells Identify Process-Specific Errors of Attentional
      Control Prior to Transient Prefrontal-Cingulate Inhibition.
AB  - Errors indicate the need to adjust attention for improved future performance.
      Detecting errors is thus a fundamental step to adjust and control attention.
      These functions have been associated with the dorsal anterior cingulate cortex
      (dACC), predicting that dACC cells should track the specific processing states
      giving rise to errors in order to identify which processing aspects need
      readjustment. Here, we tested this prediction by recording cells in the dACC and
      lateral prefrontal cortex (latPFC) of macaques performing an attention task that
      dissociated 3 processing stages. We found that, across prefrontal subareas, the
      dACC contained the largest cell populations encoding errors indicating (1)
      failures of inhibitory control of the attentional focus, (2) failures to prevent
      bottom-up distraction, and (3) lapses when implementing a choice. Error-locked
      firing in the dACC showed the earliest latencies across the PFC, emerged earlier
      than reward omission signals, and involved a significant proportion of putative
      inhibitory interneurons. Moreover, early onset error-locked response enhancement
      in the dACC was followed by transient prefrontal-cingulate inhibition, possibly
      reflecting active disengagement from task processing. These results suggest a
      functional specialization of the dACC to track and identify the actual processes
      that give rise to erroneous task outcomes, emphasizing its role to control
      attentional performance. 

PMID- 24591527
TI  - Effects of telmisartan on lipid metabolisms and proinflammatory factors secretion
      of differentiated 3T3-L1 adipocytes.
AB  - AIM: To investigate the effect of telmisartan on the lipometabolisms and the
      proinflammatory factors secreted from 3T3-L1 adipocytes and to explore the
      possible mechanisms. MATERIALS AND METHODS: Telmisartan was applied to interfere
      with mature 3T3-L1 adipocytes. The culture's free fatty acids, interleukin 6 (IL
      6) and tumor necrosis factor alpha (TNFalpha) were evaluated. Oil Red O staining
      was used to determine the adipogenesis of 3T3-L1 adipocytes. (18)F-FDG uptake
      levels corrected for protein content were determined by cellular radioactivity.
      The total RNA was isolated for hybridization experimentation in the microarray.
      RESULTS: Telmisartan reduced lipid storage and increased (18)F-FDG uptake in a
      dose-dependent manner, reduced the levels of IL-6 and TNFalpha and increased
      those of free fatty acids. One hundred and fifty-seven differentially expressed
      genes were found by microarray. The mitogen-activated protein kinase (MAPK)
      signaling pathway involved in the secretion of proinflammatory factor and lipid
      metabolisms was affected by telmisartan. The expression of endothelial nitric
      oxide synthetase gene 3 (Nos3) and carnitine palmitoyl transferase 1alpha
      (CPT1alpha) was up-regulated by telmisartan. CONCLUSIONS: Telmisartan affected
      lipometabolisms and the proinflammatory factors secreted from adipocytes. Nos3,
      CPT1alpha and the MAPK pathway being affected by telmisartan may be the
      underlying cause of the improvement in lipid metabolisms and secretion of
      proinflammatory factors of differentiated 3T3-L1 adipocytes.

PMID- 24591528
TI  - Inhibition of cellular transdifferentiation by losartan minimizes but does not
      reverse type 2 diabetes-induced renal fibrosis.
AB  - HYPOTHESIS/INTRODUCTION: Transformer Growth Factor (TGF-beta1) and angiotensin II
      (AngII) induce epithelial mesenchymal transition (EMT) and myofibroblastic
      transdifferentiation (MFT) contributing to renal fibrosis. The present study
      evaluated the capacity of an AT1 receptor blocker (losartan) to induce the
      regression of pre-existing fibrosis via interference with MFT and EMT in a rat
      model of type 2 diabetes, and in cultured mesangial cells (MCs) stimulated with
      high glucose and AngII. MATERIALS AND METHODS: After 12 weeks of diabetes
      induction (D12 group), animals showing evidence of nephropathy, were divided in
      groups untreated for additional 8 weeks (D20 group) and treated for additional 8
      weeks with losartan (D20+los group). RESULTS: D12 animals presented
      hyperglycemia, insulin resistance, hypertension, proteinuria, increased levels of
      TGF-beta1 and MFT/EMT markers. Losartan stabilized all of these parameters and
      hindered the progression of fibrosis, but it did not reverse the pre-existing
      fibrotic manifestations. Losartan reduced TGF-beta1 in the tubules, but not in
      the glomeruli. Stimulated MC exhibited myofibroblast phenotype and capacity for
      migration, which were completely reversed by losartan. CONCLUSIONS: Cellular
      transition may play a role in diabetes-inducing renal fibrogenesis in both AngII
      TGF-beta1 axis-dependent and independent manners. Losartan was efficient in
      preventing cells from undergoing further transdifferentiation, but this strategy
      was not sufficient to induce regression of the pre-existing tissue fibrosis.

PMID- 24591529
TI  - Binding of prorenin to (pro)renin receptor induces the proliferation of human
      umbilical artery smooth muscle cells via ROS generation and ERK1/2 activation.
AB  - INTRODUCTION: Since the discovery of the (pro)renin receptor (PRR), it has been
      considered as a novel bioactive molecule of the renin-angiotensin system (RAS).
      The activation of PRR can elicit a series of angiotensin II (AngII)-independent
      effects. MATERIALS AND METHODS: In this study, we investigated the effects of
      prorenin and PRR on the proliferation of human umbilical artery smooth muscle
      (HUASM) cells and explored the possible mechanisms underlying these effects.
      RESULTS: The binding of prorenin to PRR can promote proliferation and upregulate
      the anti-apoptotic protein Bcl-2 and downregulate the pro-apoptotic protein Bax
      independently of AngII in HUASM cells. In addition, the binding of prorenin to
      PRR can also increase the production of reactive oxygen species (ROS) and the
      phosphorylation of extracellular signal-regulated kinase (ERK1/2) independently
      of AngII. The pretreatment of HUASM cells with an NADPH oxidase inhibitor DPI
      decreased the production of ROS and also decreased the phosphorylation of ERK1/2.
      Furthermore, pretreatment of HUASM cells with DPI and the ERK1/2 inhibitor
      PD98059 significantly attenuated the prorenin-induced proliferation and
      regulation of apoptosis factors. CONCLUSION: Binding of prorenin to PRR can
      induce HUASM cell proliferation via the ROS generation and ERK1/2 activation.

PMID- 24591530
TI  - Angiotensin-converting enzyme insertion/deletion gene polymorphism is associated
      with dermatomyositis.
AB  - BACKGROUND AND OBJECTIVE: The cornerstone of dermatomyositis (DM) pathogenesis
      involves vascular disturbance that leads to hypoxia, capillary necrosis and
      muscle perifascicular atrophy. Hence, the hypothesis is that the angiotensin
      converting enzyme (ACE) insertion/deletion (I/D) gene polymorphism could be
      associated with susceptibility to DM. METHOD: A single centre, case control study
      that genotyped ACE gene in 88 DM and 99 healthy individuals. The ACE gene
      polymorphism was determined by melting curve analysis of real-time polymerase
      chain reaction products using SYBR Green. RESULTS: The DM and the control
      subjects had a comparable mean age, gender frequency and ethnicity. The frequency
      of the D allele was higher in DM than in the control individuals (63.6% vs 55.6%,
      respectively). The DM had more ACE D/D and less ACE I/D genotype when compared to
      the control individuals, whereas the ACE I/I genotype distribution was similar in
      both case and control groups. Moreover, after sex-age-adjusted analysis, the ACE
      D/D genotype was strongly associated with DM disease (odds ratio (OR) 2.44, 95%
      confidence interval (CI): 1.17-4.37), in contrast to ACE I/D genotype (OR 0.51,
      95% CI: 0.28-0.93). CONCLUSIONS: Homozygous ACE D/D was associated significantly
      with the DM risk. Further investigations are required to clarify and to confirm
      the association of these genes with DM susceptibility.

PMID- 24591531
TI  - Associations between BMI and fat taste sensitivity in humans.
AB  - The objective of this study was to examine the reliability of associations
      between fat taste, hunger, dietary fat intake, and body mass index (BMI).
      Detection thresholds for oleic acid (OA) were obtained during each of 7
      consecutive visits using a modified staircase procedure. Participants were 48 (N
      = 17 male; N = 31 female) healthy adults (mean age: 28.5 +/- 10.4 years) with
      BMI's ranging from 18.9 to 47.2 (>= 25 kg . m(-2), N = 24). OA detection
      thresholds and self-reported hunger (100-mm visual analog scale) were assessed at
      each visit. BMI and dietary fat intake (Block Rapid Fat Screener) were determined
      at baseline. There was a significant decrease of threshold concentration over
      repeated trials among lean and overweight (BMI between 25.0 and 29.9 kg . m(-2))
      participants but not in the obese. Combining the lean and overweight and
      contrasting their responses to the obese revealed the lean plus overweight group
      to be significantly more sensitive at visits 6 and 7. No change of threshold
      sensitivity or correlation with fat intake was observed in the obese participants
      unlike findings in the lean and lean plus overweight participants. Correlations
      between saturated fat intake and threshold sensitivity were positive (greater
      intake associated with higher thresholds) at baseline for the group, with
      additional correlations observed among the lean plus overweight but not in the
      obese, leaving open questions about the nutritional significance of the
      association. No significant associations were observed between sensitivity to OA
      and hunger. Repeated testing is required to assess associations between fat taste
      and other outcome variables.

PMID- 24591532
TI  - Optical coherence tomography and visual evoked potentials: which is more
      sensitive in multiple sclerosis?
AB  - OBJECTIVE: To assess the sensitivity of optic coherence tomography (OCT) and
      visual evoked potentials (VEPs) to visual pathway abnormalities in multiple
      sclerosis (MS). METHODS: A total of 40 MS subjects, 28 with optic neuritis (ON)
      at least 3 months before (bilateral in 5), underwent assessment of visual acuity,
      Expanded Disability Status Scale (EDSS), OCT and VEPs, the latter quantified with
      a 0-4 conventional score. RESULTS: OCT and VEPs were abnormal in 36% and 56%
      respectively in all eyes (p=0.11), 68% and 86% in eyes with previous ON (p=0.12),
      and in 19% versus 40% in eyes without ON history (p=0.007). Combining VEP and OCT
      increased sensitivity to 89% in ON and 44% in non-ON eyes. Considering all eyes,
      global retinal nerve fibre layer (RNFL) thickness and VEP score were
      significantly correlated between them (rho=-0.63, p<0.001) and with EDSS (RNFL:
      rho=0.40, p<0.001; VEP score: rho=0.47, p<0.001). Disease duration correlated
      with VEP score (rho=0.25, p=0.025) and RNFL thickness (rho=-0.71, p<0.001).
      CONCLUSIONS: In eyes without ON, VEPs were more frequently abnormal than OCT,
      while the two techniques showed similar sensitivity in eyes previously affected
      by ON. The correlation of VEPs and OCT measures with disability prompts further
      exploration of the two techniques as potential markers of disease burden.

PMID- 24591533
TI  - An overview of alopecias.
AB  - Hair loss is a topic of enormous public interest and understanding the
      pathophysiology and treatment of various alopecias will likely make a large
      impact on patients' lives. The investigation of alopecias also provides important
      insight in the basic sciences; for instance, the abundance of stem cell
      populations and regenerative cycles that characterize a hair follicle render it
      an excellent model for the study of stem cell biology. This review seeks to
      provide a concise summary of the major alopecias with regard to presentation and
      management, and correlate these to recent advances in relevant research on
      pathogenesis. 

PMID- 24591534
TI  - Myocardial tissue engineering: in vitro models.
AB  - Modeling integrated human physiology in vitro is a formidable task not yet
      achieved with any of the existing cell/tissue systems. However, tissue
      engineering is becoming increasingly successful at authentic representation of
      the actual environmental milieu of tissue development, regeneration and disease
      progression, and in providing real-time insights into morphogenic events.
      Functional human tissue units engineered to combine biological fidelity with the
      high-throughput screening and real-time measurement of physiological responses
      are poised to transform drug screening and predictive modeling of disease. In
      this review, we focus on the in vitro engineering of functional human myocardium
      that mimics heart tissue for analysis of myocardial function, in the context of
      physiological studies, drug screening for therapeutics, and safety pharmacology. 

PMID- 24591535
TI  - Synthetic lethal screens as a means to understand and treat MYC-driven cancers.
AB  - Although therapeutics against MYC could potentially be used against a wide range
      of human cancers, MYC-targeted therapies have proven difficult to develop. The
      convergence of breakthroughs in human genomics and in gene silencing using RNA
      interference (RNAi) have recently allowed functional interrogation of the genome
      and systematic identification of synthetic lethal interactions with hyperactive
      MYC. Here, we focus on the pathways that have emerged through RNAi screens and
      present evidence that a subset of genes showing synthetic lethality with MYC are
      significantly interconnected and linked to chromatin and transcriptional
      processes, as well as to DNA repair and cell cycle checkpoints. Other synthetic
      lethal interactions with MYC point to novel pathways and potentially broaden the
      repertoire of targeted therapies. The elucidation of MYC synthetic lethal
      interactions is still in its infancy, and how these interactions may be
      influenced by tissue-specific programs and by concurrent genetic change will
      require further investigation. Nevertheless, we predict that these studies may
      lead the way to novel therapeutic approaches and new insights into the role of
      MYC in cancer. 

PMID- 24591538
TI  - Condensation dynamics of the L-Pro-L-Phe and L-Hyp-L-Phe binary mixtures in
      solution.
AB  - We employ the achiral liquid chromatography with diode array, evaporative light
      scattering and mass spectrometric detection (HPLC-DAD, HPLC-ELSD and LC-MS) to
      assess structural instability (understood as spontaneous oscillatory chiral
      conversion and spontaneous oscillatory condensation) of the two pairs of amino
      acids, L-proline-L-phenylalanine (L-Pro-L-Phe) and L-hydroxyproline-L
      phenylalanine (L-Hyp-L-Phe), in aqueous acetonitrile. In our earlier studies, we
      managed to demonstrate that single amino acids in aqueous and non-aqueous
      solutions undergo spontaneous oscillatory chiral conversion and oscillatory
      condensation. We also investigated condensation in the binary L-Pro-L-Hyp mixture
      in aqueous solution, and proposed a theoretical model to explain the specific
      dynamics of this process, which involves mutual catalytic effects of the two
      amino acids. In this study, we demonstrate oscillatory instability with the other
      two amino acid pairs in the organic-aqueous solution and reflect on the dynamics
      of condensation in the investigated cases. The choice of L-Pro and L-Hyp is due
      to their important role as building blocks of collagen, which is omnipresent in
      the connective tissues of mammals, and largely responsible for tissue
      architecture and strength. L-Phe is one of the 20 exogenous amino acids and is a
      building block of the majority of naturally occurring proteins.

PMID- 24591536
TI  - MYC degradation.
AB  - The MYC oncoprotein is an essential transcription factor that regulates the
      expression of many genes involved in cell growth, proliferation, and metabolic
      pathways. Thus, it is important to keep MYC activity in check in normal cells in
      order to avoid unwanted oncogenic changes. Normal cells have adapted several ways
      to control MYC levels, and these mechanisms can be disrupted in cancer cells. One
      of the major ways in which MYC levels are controlled in cells is through targeted
      degradation by the ubiquitin-proteasome system (UPS). Here, we discuss the role
      of the UPS in the regulation of MYC protein levels and review some of the many
      proteins that have been shown to regulate MYC protein stability. In addition, we
      discuss how this relates to MYC transcriptional activity, human cancers, and
      therapeutic targeting. 

PMID- 24591539
TI  - Simultaneous quantification of six constituents in Qing-huo-zhi-mai tablet by
      high-performance liquid chromatography-tandem mass spectrometry.
AB  - A novel sensitive and specific high-performance liquid chromatography-tandem mass
      spectrometry method was established for the simultaneous determination of six
      constituents including geniposide, andrographolide, dehydroandrographolide,
      ophiopogonin D, methylophiopogonanone A and methylophiopogonanone B in Qing-huo
      zhi-mai (QHZM) tablet, a well-known Chinese herbal preparation. The
      chromatographic separation was performed on a C18 column, and the mobile phase
      was composed of 0.04% acetic acid and acetonitrile with gradient elution. The
      detection of analytes was carried out by multiple reaction monitoring scanning
      with switching electrospray ion source polarity between positive and negative
      modes in a single run. The total run time was 15 min. The calibration curves were
      linear with all correlation coefficients >0.9979 in the tested ranges. The intra-
      and interday variations were no >7.0%, and the average recoveries were in the
      range of 93.2-108.5% with the relative standard deviations no >5.4%. The
      developed method was successfully employed to analyze five batches of QHZM tablet
      samples. This is the first time for the determination of ophiopogonin D,
      methylophiopogonanone A and methylophiopogonanone B in QHZM tablets. 

PMID- 24591540
TI  - Brugada syndrome ECG is highly prevalent in schizophrenia.
AB  - BACKGROUND: The causes of increased risk of sudden cardiac death in schizophrenia
      are not resolved. We aimed to establish (1) whether ECG markers of sudden cardiac
      death risk, in particular Brugada-ECG pattern, are more prevalent among patients
      with schizophrenia, and (2) whether increased prevalence of these ECG markers in
      schizophrenia is explained by confounding factors, notably sodium channel
      blocking medication. METHODS AND RESULTS: In a cross-sectional study, we analyzed
      ECGs of a cohort of 275 patients with schizophrenia, along with medication use.
      We determined whether Brugada-ECG was present and assessed standard ECG measures
      (heart rate, PQ-, QRS-, and QT-intervals). We compared the findings with
      nonschizophrenic individuals of comparable age (the Netherlands Study of
      Depression and Anxiety [NESDA] cohort; N=179) and, to account for assumed
      increased aging rate in schizophrenia, with individuals 20 years older (Hoorn
      cohort; n=1168), using multivariate regression models. Brugada-ECG was
      significantly more prevalent in the schizophrenia cohort (11.6%) compared with
      NESDA controls (1.1%) or Hoorn controls (2.4%). Moreover, patients with
      schizophrenia had longer QT-intervals (410.9 versus 393.1 and 401.9 ms; both
      P<0.05), increased proportion of mild or severe QTc prolongation (13.1% and 5.8%
      versus 3.4% and 0.0% [NESDA], versus 5.1 and 2.8% [Hoorn]), and higher heart
      rates (80.8 versus 61.7 and 68.0 beats per minute; both P<0.05). The prevalence
      of Brugada-ECG was still increased (9.6%) when patients with schizophrenia
      without sodium channel-blocking medication were compared with either of the
      control cohorts. CONCLUSIONS: Brugada-ECG has increased prevalence among patients
      with schizophrenia. This association is not explained by the use of sodium
      channel-blocking medication.

PMID- 24591541
TI  - Tight glycaemic control does not improve mortality or morbidity in critically ill
      children.

PMID- 24591537
TI  - Adipocytes in skin health and disease.
AB  - Adipocytes are intimately associated with the dermal compartment of the skin,
      existing in a specialized dermal depot and displaying dynamic changes in size
      during tissue homeostasis. However, the roles of adipocytes in cutaneous biology
      and disease are not well understood. Traditionally, adipocytes within tissues
      were thought to act as reservoirs of energy, as thermal, or as structural
      support. In this review, we discuss recent studies revealing the cellular basis
      of the dynamic development and regenerative capacity of dermal adipocytes
      associated with the hair cycle and following injury. We discuss and speculate on
      potential roles of dermal adipocytes in cutaneous biology with an emphasis on
      communication during hair follicle growth and wound healing. Finally, we explore
      how alterations in the dermal adipose tissue may support clinical manifestations
      of cutaneous diseases such as lipodystrophy, obesity, and alopecia. 

PMID- 24591542
TI  - An 'all-human' diet decreases days of parenteral nutrition compared with formula
      in premature infants.

PMID- 24591543
TI  - Voided midstream urine culture is a good test for acute cystitis in premenopausal
      women.

PMID- 24591544
TI  - In young men, various risk factors are associated with later development of young
      onset dementia.

PMID- 24591545
TI  - In people with ultra high risk symptoms, risk of transition to psychotic
      disorders is highest in the first 2 years.

PMID- 24591546
TI  - Review: psychosocial mood management improves smoking cessation in people with
      current and past depression.

PMID- 24591547
TI  - Behavioural treatment combined with buprenorphine does not reduce opioid use
      compared with buprenorphine alone.

PMID- 24591548
TI  - Caring behaviour of nurses in Malaysia is influenced by spiritual and emotional
      intelligence, psychological ownership and burnout.

PMID- 24591549
TI  - The hostile heart: anger as a trigger for acute cardiovascular events.

PMID- 24591550
TI  - Outbursts of anger as a trigger of acute cardiovascular events: a systematic
      review and meta-analysis.
AB  - AIM: Short-term psychological stress is associated with an immediate
      physiological response and may be associated with a transiently higher risk of
      cardiovascular events. The aim of this study was to determine whether brief
      episodes of anger trigger the onset of acute myocardial infarction (MI), acute
      coronary syndromes (ACS), ischaemic and haemorrhagic stroke, and ventricular
      arrhythmia. METHODS AND RESULTS: We performed a systematic review of studies
      evaluating whether outbursts of anger are associated with the short-term risk of
      heart attacks, strokes, and disturbances in cardiac rhythm that occur in everyday
      life. We performed a literature search of the CINAHL, Embase, PubMed, and
      PsycINFO databases from January 1966 to June 2013 and reviewed the reference
      lists of retrieved articles and included meeting abstracts and unpublished
      results from experts in the field. Incidence rate ratios and 95% confidence
      intervals were calculated with inverse-variance-weighted random-effect models.
      The systematic review included nine independent case-crossover studies of anger
      outbursts and MI/ACS (four studies), ischaemic stroke (two studies), ruptured
      intracranial aneurysm (one study), and ventricular arrhythmia (two studies).
      There was evidence of substantial heterogeneity between the studies (I(2) = 92.5%
      for MI/ACS and 89.8% for ischaemic stroke). Despite the heterogeneity, all
      studies found that, compared with other times, there was a higher rate of
      cardiovascular events in the 2h following outbursts of anger. CONCLUSION: There
      is a higher risk of cardiovascular events shortly after outbursts of anger.

PMID- 24591551
TI  - Influence of a positive family history of both type 2 diabetes and PCOS on
      metabolic and endocrine parameters in a large cohort of PCOS women.
AB  - OBJECTIVE: There is evidence suggesting a strong genetic background of polycystic
      ovary syndrome (PCOS). We aim to study the metabolic and endocrine
      characteristics of PCOS women with and without a family history (FHx) of type 2
      diabetes mellitus (T2DM) and PCOS. DESIGN: Cross-sectional study. METHODS: We
      analysed the association of T2DM FHx and PCOS FHx with metabolic and endocrine
      parameters in 714 PCOS women. RESULTS: A positive FHx of T2DM and PCOS were
      prevalent in 36.8 and 21.4% of PCOS women respectively. We found an independent
      association of T2DM FHx with central fat accumulation, obesity, prediabetes,
      metabolic syndrome (MS), insulin resistance, low HDL and elevated blood pressure
      (P<0.05 for all). PCOS FHx was independently associated with prediabetes
      (P<0.05). We observed an independent association of PCOS FHx with clinical and
      biochemical hyperandrogenism (P<0.05 for all), whereas there was no independent
      association of T2DM FHx with hyperandrogenism. PCOS women with a positive FHx of
      both T2DM and PCOS had an adverse metabolic and endocrine profile including a
      linear increase in risk of obesity, central fat accumulation, MS, prediabetes and
      low HDL (P<0.05 for all). CONCLUSIONS: Our findings suggest that the assessment
      of FHx might allow risk stratification of PCOS women, which is important
      considering the high prevalence of PCOS.

PMID- 24591552
TI  - Patients lost to follow-up in acromegaly: results of the ACROSPECT study.
AB  - OBJECTIVE: The complex management of acromegaly has transformed this disease into
      a chronic condition, with the risk of patients being lost to follow-up. The
      objective of this study was to estimate the proportion of acromegalic patients
      lost to follow-up in France and to determine the impact that abandoning follow-up
      has on the disease and its management. DESIGN: ACROSPECT was a French national,
      multicentre, cross-sectional, observational study. METHODS: Acromegalic patients
      were considered lost to follow-up if no new information had been entered in their
      hospital records during the previous 2 years. They were traced where possible,
      and data were collected by means of a recall visit or questionnaire. RESULTS: In
      the study population, 21% of the 2392 acromegalic patients initially followed in
      25 tertiary endocrinology centres were lost to follow-up. At their last follow-up
      visit, 30% were uncontrolled, 33% were receiving medical therapy and 53% had
      residual tumour. Of the 362 traced, 62 had died and 77% were receiving follow-up
      elsewhere; the leading reason for abandoning follow-up was that they had not been
      informed that it was necessary. Our analysis of the questionnaires suggests that
      they were not receiving optimal follow-up. CONCLUSIONS: This study underlines the
      need to better inform acromegalic patients of the need for long-term follow-up,
      the absence of which could be detrimental to patients' health, and to develop
      shared care for what must now be regarded as a chronic disease.

PMID- 24591555
TI  - Organization to promote biomarker development.

PMID- 24591553
TI  - Analysis of the gene coding for steroidogenic factor 1 (SF1, NR5A1) in a cohort
      of 50 Egyptian patients with 46,XY disorders of sex development.
AB  - OBJECTIVE: Steroidogenic factor 1 (SF1, NR5A1) is a key transcriptional regulator
      of genes involved in the hypothalamic-pituitary-gonadal axis. Recently, SF1
      mutations were found to be a frequent cause of 46,XY disorders of sex development
      (DSD) in humans. We investigate the frequency of NR5A1 mutations in an Egyptian
      cohort of XY DSD. DESIGN: Clinical assessment, endocrine evaluation and genetic
      analysis of 50 Egyptian XY DSD patients (without adrenal insufficiency) with a
      wide phenotypic spectrum. METHODS: Molecular analysis of NR5A1 gene by direct
      sequencing followed by in vitro functional analysis of the two novel missense
      mutations detected. RESULTS: Three novel heterozygous mutations of the coding
      region in patients with hypospadias were detected. p.Glu121AlafsX25 results in
      severely truncated protein, p.Arg62Cys lies in DNA-binding zinc finger, whereas
      p.Ala154Thr lies in the hinge region of SF1 protein. Transactivation assays using
      reporter constructs carrying promoters of anti-Mullerian hormone (AMH), CYP11A1
      and TESCO core enhancer of Sox9 showed that p.Ala154Thr and p.Arg62Cys mutations
      result in aberrant biological activity of NR5A1. A total of 17 patients (34%)
      harboured the p.Gly146Ala polymorphism. CONCLUSION: We identified two novel NR5A1
      mutations showing impaired function in 23 Egyptian XY DSD patients with
      hypospadias (8.5%). This is the first study searching for NR5A1 mutations in
      oriental patients from the Middle East and Arab region with XY DSD and no adrenal
      insufficiency, revealing a frequency similar to that in European patients (6.5
      15%). We recommend screening of NR5A1 in patients with hypospadias and gonadal
      dysgenesis. Yearly follow-ups of gonadal function and early cryoconservation of
      sperms should be performed in XY DSD patients with NR5A1 mutations given the risk
      of future fertility problems due to early gonadal failure.

PMID- 24591556
TI  - NIH FOA focuses on future BRAIN research.

PMID- 24591558
TI  - New/Revised diagnostic imaging standards from Joint Commission.

PMID- 24591562
TI  - Open access.

PMID- 24591564
TI  - Genome-wide analysis reveals a role for BRCA1 and PALB2 in transcriptional co
      activation.
AB  - Breast and ovarian cancer susceptibility genes BRCA1 and PALB2 have enigmatic
      roles in cellular growth and mammalian development. While these genes are
      essential for growth during early developmental programs, inactivation later in
      adulthood results in increased growth and formation of tumors, leading to their
      designation as tumor suppressors. We performed genome-wide analysis assessing
      their chromatin residence and gene expression responsiveness using high
      throughput sequencing in breast epithelial cells. We found an intimate
      association between BRCA1 and PALB2 chromatin residence and genes displaying high
      transcriptional activity. Moreover, our experiments revealed a critical role for
      BRCA1 and, to a smaller degree, PALB2 in transcriptional responsiveness to NF
      kappaB, a crucial mediator of growth and inflammatory response during development
      and cancer. Importantly, we also uncovered a vital role for BRCA1 and PALB2 in
      response to retinoic acid (RA), a growth inhibitory signal in breast cancer
      cells, which may constitute the basis for their tumor suppressor activity. Taken
      together, our results highlight an important role for these breast cancer
      proteins in the regulation of diverse growth regulatory pathways. 

PMID- 24591565
TI  - Surface dynamics of GluN2B-NMDA receptors controls plasticity of maturing
      glutamate synapses.
AB  - NMDA-type glutamate receptors (NMDAR) are central actors in the plasticity of
      excitatory synapses. During adaptive processes, the number and composition of
      synaptic NMDAR can be rapidly modified, as in neonatal hippocampal synapses where
      a switch from predominant GluN2B- to GluN2A-containing receptors is observed
      after the induction of long-term potentiation (LTP). However, the cellular
      pathways by which surface NMDAR subtypes are dynamically regulated during
      activity-dependent synaptic adaptations remain poorly understood. Using a
      combination of high-resolution single nanoparticle imaging and electrophysiology,
      we show here that GluN2B-NMDAR are dynamically redistributed away from glutamate
      synapses through increased lateral diffusion during LTP in immature neurons.
      Strikingly, preventing this activity-dependent GluN2B-NMDAR surface
      redistribution through cross-linking, either with commercial or with autoimmune
      anti-NMDA antibodies from patient with neuropsychiatric symptoms, affects the
      dynamics and spine accumulation of CaMKII and impairs LTP. Interestingly, the
      same impairments are observed when expressing a mutant of GluN2B-NMDAR unable to
      bind CaMKII. We thus uncover a non-canonical mechanism by which GluN2B-NMDAR
      surface dynamics plays a critical role in the plasticity of maturing synapses
      through a direct interplay with CaMKII. 

PMID- 24591566
TI  - Color and brightness encoded in a common L- and M-cone pathway with expansive and
      compressive nonlinearities.
AB  - Lights near 560 nm appear brighter when flickered, whereas lights near 520 or 650
      nm appear yellower. Both effects are consistent with signal distortion within the
      visual pathway--brightness changes at an expansive nonlinearity, and hue shifts
      at a compressive one. We previously manipulated the distortion products generated
      by each nonlinearity to extract the temporal properties of stages of the L- and M
      cone pathways that signal brightness and color before (early stages) and after
      (late stages) each nonlinearity. We find that the attenuation characteristics of
      the early and late stages are virtually identical in both pathways: The early
      temporal stage acts like a band-pass filter peaking at 10-15 Hz, while the late
      stage acts like low-pass filter with a cut-off frequency near 3 Hz. We propose a
      physiologically relevant model that accounts for the filter shapes and
      incorporates both nonlinearities within a common parvocellular pathway. The shape
      of the early band-pass filter is consistent with antagonism between center
      signals and more sluggish and delayed surround signals, while the late filter is
      consistent with a simple two-stage low-pass filter. Modeling suggests that the
      brightness change and hue shift are both initially caused by the half-wave
      rectification and partition of signals into ON and OFF components. However, the
      hue shift is probably caused by the additional effects of a later nonlinearity
      that compresses chromatic red and green signals. Plausible sites for the
      expansive half-wave rectifying nonlinearity are after surround antagonism,
      possibly from horizontal cells, but the compressive nonlinearity is likely to be
      after the late filter.

PMID- 24591567
TI  - Dynamic illusory size contrast: a relative-size illusion modulated by stimulus
      motion and eye movements.
AB  - We present a novel size-contrast illusion that depends on the dynamic nature of
      the stimulus. In the dynamic illusory size-contrast (DISC) effect, the viewer
      perceives the size of a target bar to be shrinking when it is surrounded by an
      expanding box and when there are additional dynamic cues such as eye movements,
      changes in retinal eccentricity of the bar, or changes in the spatial position of
      the bar. Importantly, the expanding box was necessary but not sufficient to
      obtain an illusory percept, distinguishing the DISC effect from other size
      contrast illusions. We propose that the visual system is weighting the different
      sources of information that contribute to size perception based on the level of
      uncertainty in the retinal image size of the object. Whereas the growing box
      normally has a weak influence on the perceived size of the target bar, this
      influence is enhanced when other dynamic changes in the environment (e.g., eye
      movements, changes in retinal eccentricity, and target motion) lead to
      uncertainty in the retinal size of the target bar. Given the compelling nature of
      the DISC effect and the inherently dynamic nature of our environment, these
      factors are likely to play an important role in everyday size judgments. 

PMID- 24591569
TI  - So, doctor, was I worth L10?

PMID- 24591568
TI  - FIP5 phosphorylation during mitosis regulates apical trafficking and
      lumenogenesis.
AB  - Apical lumen formation is a key step during epithelial morphogenesis. The
      establishment of the apical lumen is a complex process that involves coordinated
      changes in plasma membrane composition, endocytic transport, and cytoskeleton
      organization. These changes are accomplished, at least in part, by the targeting
      and fusion of Rab11/FIP5-containing apical endosomes with the apical membrane
      initiation site (AMIS). Although AMIS formation and polarized transport of
      Rab11/FIP5-containing endosomes are crucial for the formation of a single apical
      lumen, the spatiotemporal regulation of this process remains poorly understood.
      Here, we demonstrate that the formation of the midbody during cytokinesis is a
      symmetry-breaking event that establishes the location of the AMIS. The
      interaction of FIP5 with SNX18, which is required for the formation of apical
      endocytic carriers, is inhibited by GSK-3 phosphorylation at FIP5-T276.
      Importantly, we show that FIP5-T276 phosphorylation occurs specifically during
      metaphase and anaphase, to ensure the fidelity and timing of FIP5-endosome
      targeting to the AMIS during apical lumen formation. 

PMID- 24591570
TI  - Emergence of sigh rhythmogenesis in the embryonic mouse.
AB  - In mammals, eupnoeic breathing is periodically interrupted by spontaneous
      augmented breaths (sighs) that include a larger-amplitude inspiratory effort,
      typically followed by a post-sigh apnoea. Previous in vitro studies in newborn
      rodents have demonstrated that the respiratory oscillator of the pre-Botzinger
      complex (preBotC) can generate the distinct inspiratory motor patterns for both
      eupnoea- and sigh-related behaviour. During mouse embryonic development, the
      preBotC begins to generate eupnoeic rhythmicity at embryonic day (E) 15.5, but
      the network's ability to also generate sigh-like activity remains unexplored at
      prenatal stages. Using transverse brainstem slice preparations we monitored the
      neuronal population activity of the preBotC at different embryonic ages.
      Spontaneous sigh-like rhythmicity was found to emerge progressively, being
      expressed in 0/32 slices at E15.5, 7/30 at E16.5, 9/22 at E17.5 and 23/26 at
      E18.5. Calcium imaging showed that the preBotC cell population that participates
      in eupnoeic-like discharge was also active during fictive sighs. However, patch
      clamp recordings revealed the existence of an additional small subset of neurons
      that fired exclusively during sigh activity. Changes in glycinergic inhibitory
      synaptic signalling, either by pharmacological blockade, functional perturbation
      or natural maturation of the chloride co-transporters KCC2 or NKCC1 selectively,
      and in an age-dependent manner, altered the bi-phasic nature of sigh bursts and
      their coordination with eupnoeic bursting, leading to the generation of an
      atypical monophasic sigh-related event. Together our results demonstrate that the
      developmental emergence of a sigh-generating capability occurs after the onset of
      eupnoeic rhythmogenesis and requires the proper maturation of chloride-mediated
      glycinergic synaptic transmission. 

PMID- 24591571
TI  - Computational analysis of Ca2+ dynamics in isolated cardiac mitochondria predicts
      two distinct modes of Ca2+ uptake.
AB  - Cardiac mitochondria can act as a significant Ca(2+) sink and shape cytosolic
      Ca(2+) signals affecting various cellular processes, such as energy metabolism
      and excitation-contraction coupling. However, different mitochondrial Ca(2+)
      uptake mechanisms are still not well understood. In this study, we analysed
      recently published Ca(2+) uptake experiments performed on isolated guinea pig
      cardiac mitochondria using a computer model of mitochondrial bioenergetics and
      cation handling. The model analyses of the data suggest that the majority of
      mitochondrial Ca(2+) uptake, at physiological levels of cytosolic Ca(2+) and
      Mg(2+), occurs through a fast Ca(2+) uptake pathway, which is neither the Ca(2+)
      uniporter nor the rapid mode of Ca(2+) uptake. This fast Ca(2+) uptake component
      was explained by including a biophysical model of the ryanodine receptor (RyR) in
      the computer model. However, the Mg(2+)-dependent enhancement of the RyR
      adaptation was not evident in this RyR-type channel, in contrast to that of
      cardiac sarcoplasmic reticulum RyR. The extended computer model is corroborated
      by simulating an independent experimental dataset, featuring mitochondrial Ca(2+)
      uptake, egress and sequestration. The model analyses of the two datasets validate
      the existence of two classes of Ca(2+) buffers that comprise the mitochondrial
      Ca(2+) sequestration system. The modelling study further indicates that the
      Ca(2+) buffers respond differentially depending on the source of Ca(2+) uptake.
      In particular, it suggests that the Class 1 Ca(2+) buffering capacity is auto
      regulated by the rate at which Ca(2+) is taken up by mitochondria. 

PMID- 24591572
TI  - Increase in cytosolic Ca2+ produced by hypoxia and other depolarizing stimuli
      activates a non-selective cation channel in chemoreceptor cells of rat carotid
      body.
AB  - The current model of O2 sensing by carotid body chemoreceptor (glomus) cells is
      that hypoxia inhibits the outward K(+) current and causes cell depolarization,
      Ca(2+) influx via voltage-dependent Ca(2+) channels and a rise in intracellular
      [Ca(2+)] ([Ca(2+)]i). Here we show that hypoxia (<5% O2), in addition to
      inhibiting the two-pore domain K(+) channels TASK-1/3 (TASK), indirectly
      activates an ~20 pS channel in isolated glomus cells. The 20 pS channel was
      permeable to K(+), Na(+) and Cs(+) but not to Cl(-) or Ca(2+). The 20 pS channel
      was not sensitive to voltage. Inhibition of TASK by external acid, depolarization
      of glomus cells with high external KCl (20 mm) or opening of the Ca(2+) channel
      with FPL64176 activated the 20 pS channel when 1 mm Ca(2+) was present in the
      external solution. Ca(2+) (10 MUm) applied to the cytosolic side of inside-out
      patches activated the 20 pS channel. The threshold [Ca(2+)]i for activation of
      the 20 pS channel in cell-attached patches was ~200 nm. The reversal potential of
      the 20 pS channel was estimated to be -28 mV. Our results reveal a sequential
      mechanism in which hypoxia (<5% O2) first inhibits the K(+) conductance and then
      activates a Na(+)-permeable, non-selective cation channel via depolarization
      induced rise in [Ca(2+)]i. Our results suggest that inhibition of K(+) efflux and
      stimulation of Na(+) influx both contribute to the depolarization of glomus cells
      during moderate to severe hypoxia. 

PMID- 24591573
TI  - Neurotransmitters act as paracrine signals to regulate insulin secretion from the
      human pancreatic islet.
AB  - In this symposium review we discuss the role of neurotransmitters as paracrine
      signals that regulate pancreatic islet function. A large number of
      neurotransmitters and their receptors has been identified in the islet, but
      relatively little is known about their involvement in islet biology.
      Interestingly, neurotransmitters initially thought to be present in autonomic
      axons innervating the islet are also present in endocrine cells of the human
      islet. These neurotransmitters can thus be released as paracrine signals to help
      control hormone release. Here we propose that the role of neurotransmitters may
      extend beyond controlling endocrine cell function to work as signals modulating
      vascular flow and immune responses within the islet. 

PMID- 24591574
TI  - The role of internal and external constructive processes in evolution.
AB  - The architects of the Modern Synthesis viewed development as an unfolding of a
      form already latent in the genes. However, developing organisms play a far more
      active, constructive role in both their own development and their evolution than
      the Modern Synthesis proclaims. Here we outline what is meant by constructive
      processes in development and evolution, emphasizing how constructive development
      is a shared feature of many of the research developments central to the
      developing Extended Evolutionary Synthesis. Our article draws out the parallels
      between constructive physiological processes expressed internally and in the
      external environment (niche construction), showing how in each case they play
      important and not fully recognized evolutionary roles by modifying and biasing
      natural selection. 

PMID- 24591575
TI  - Prophylactic erythropoietin exacerbates ventilation-induced lung inflammation and
      injury in preterm lambs.
AB  - Ventilation-induced lung injury (VILI) of preterm neonates probably contributes
      to the pathogenesis of bronchopulmonary dysplasia (BPD). Erythropoietin (EPO) has
      been suggested as a therapy for BPD. The aim of this study was to determine
      whether prophylactic administration of EPO reduces VILI in preterm newborn lambs.
      Lambs at 126 days of gestation (term is 147 days) were delivered and ventilated
      with a high tidal volume strategy for 15 min to cause lung injury, then received
      gentle ventilation until 2 h of age. Lambs were randomized to receive intravenous
      EPO (5000 IU kg(-1): Vent+EPO; n = 6) or phosphate-buffered saline (Vent; n = 7)
      soon after birth: unventilated controls (UVC; n = 8) did not receive ventilation
      or any treatment. Physiological parameters were recorded throughout the
      experimental procedure. Samples of lung were collected for histological and
      molecular assessment of inflammation and injury. Samples of liver were collected
      to assess the systemic acute phase response. Vent+EPO lambs received higher F IO
      2, P aO 2 and oxygenation during the first 10 min than Vent lambs. There were no
      differences in physiological indices beyond this time. Total lung injury score,
      airway wall thickness, inflammation and haemorrhage were higher in Vent+EPO lambs
      than in Vent lambs. Lung inflammation and early markers of lung and systemic
      injury were elevated in ventilated lambs relative to unventilated lambs; EPO
      administration further increased lung inflammation and markers of lung and
      systemic injury. Prophylactic EPO exacerbates VILI, which may increase the
      incidence and severity of long-term respiratory disease. More studies are
      required before EPO can be used for lung protection in preterm infants. 

PMID- 24591576
TI  - Novel approaches to determine contractile function of the isolated adult
      zebrafish ventricular cardiac myocyte.
AB  - The zebrafish (Danio rerio) has been used extensively in cardiovascular biology,
      but mainly in the study of heart development. The relative ease of its genetic
      manipulation may indicate the suitability of this species as a cost-effective
      model system for the study of cardiac contractile biology. However, whether the
      zebrafish heart is an appropriate model system for investigations pertaining to
      mammalian cardiac contractile structure-function relationships remains to be
      resolved. Myocytes were isolated from adult zebrafish hearts by enzymatic
      digestion, attached to carbon rods, and twitch force and intracellular Ca(2+)
      were measured. We observed the modulation of twitch force, but not of
      intracellular Ca(2+), by both extracellular [Ca(2+)] and sarcomere length. In
      permeabilized cells/myofibrils, we found robust myofilament length-dependent
      activation. Moreover, modulation of myofilament activation-relaxation and force
      redevelopment kinetics by varied Ca(2+) activation levels resembled that found
      previously in mammalian myofilaments. We conclude that the zebrafish is a valid
      model system for the study of cardiac contractile structure-function
      relationships. 

PMID- 24591577
TI  - Subcellular distribution of glycogen and decreased tetanic Ca2+ in fatigued
      single intact mouse muscle fibres.
AB  - In skeletal muscle fibres, glycogen has been shown to be stored at different
      subcellular locations: (i) between the myofibrils (intermyofibrillar); (ii)
      within the myofibrils (intramyofibrillar); and (iii) subsarcolemmal. Of these,
      intramyofibrillar glycogen has been implied as a critical regulator of
      sarcoplasmic reticulum Ca(2+) release. The aim of the present study was to test
      directly how the decrease in cytoplasmic free Ca(2+) ([Ca(2+)]i) during repeated
      tetanic contractions relates to the subcellular glycogen distribution. Single
      fibres of mouse flexor digitorum brevis muscles were fatigued with 70 Hz, 350 ms
      tetani given at 2 s (high-intensity fatigue, HIF) or 10 s (low-intensity fatigue,
      LIF) intervals, while force and [Ca(2+)]i were measured. Stimulation continued
      until force decreased to 30% of its initial value. Fibres were then prepared for
      analyses of subcellular glycogen distribution by transmission electron
      microscopy. At fatigue, tetanic [Ca(2+)]i was reduced to 70 +/- 4% and 54 +/- 4%
      of the initial in HIF (P < 0.01, n = 9) and LIF (P < 0.01, n = 5) fibres,
      respectively. At fatigue, the mean inter- and intramyofibrillar glycogen content
      was 60-75% lower than in rested control fibres (P < 0.05), whereas subsarcolemmal
      glycogen was similar to control. Individual fibres showed a good correlation
      between the fatigue-induced decrease in tetanic [Ca(2+)]i and the reduction in
      intermyofibrillar (P = 0.051) and intramyofibrillar (P = 0.0008) glycogen. In
      conclusion, the fatigue-induced decrease in tetanic [Ca(2+)]i, and hence force,
      is accompanied by major reductions in inter- and intramyofibrillar glycogen. The
      stronger correlation between decreased tetanic [Ca(2+)]i and reduced
      intramyofibrillar glycogen implies that sarcoplasmic reticulum Ca(2+) release
      critically depends on energy supply from the intramyofibrillar glycogen pool. 

PMID- 24591578
TI  - Revertant mutants modify, but do not rescue, the gating defect of the cystic
      fibrosis mutant G551D-CFTR.
AB  - Cystic fibrosis (CF) is caused by dysfunction of the epithelial anion channel
      cystic fibrosis transmembrane conductance regulator (CFTR). One strategy to
      restore function to CF mutants is to suppress defects in CFTR processing and
      function using revertant mutations. Here, we investigate the effects of the
      revertant mutations G550E and 4RK (the simultaneous disruption of four arginine
      framed tripeptides (AFTs): R29K, R516K, R555K and R766K) on the CF mutant G551D,
      which impairs severely channel gating without altering protein processing and
      which affects a residue in the same alpha-helix as G550 and R555. Both G550E and
      4RK augmented strongly CFTR-mediated iodide efflux from BHK cells expressing
      G551D-CFTR. To learn how revertant mutations influence G551D-CFTR function, we
      studied protein processing and single-channel behaviour. Neither G550E nor 4RK
      altered the expression and maturation of G551D-CFTR protein. By contrast, both
      revertants had marked effects on G551D-CFTR channel gating, increasing strongly
      opening frequency, while 4RK also diminished noticeably the duration of channel
      openings. Because G551D-CFTR channel gating is ATP independent, we investigated
      whether revertant mutations restore ATP dependence to G551D-CFTR. Like wild-type
      CFTR, the activity of 4RK-G551D-CFTR varied with ATP concentration, suggesting
      that 4RK confers some ATP dependence on the G551D-CFTR channel. Thus, the
      revertant mutations G550E and 4RK alter the gating pattern and ATP dependence of
      G551D-CFTR without restoring single-channel activity to wild-type levels. Based
      on their impact on the CF mutants F508del and G551D, we conclude that G550E and
      4RK have direct effects on CFTR structure, but that their action on CFTR
      processing and channel function is CF mutation specific. 

PMID- 24591579
TI  - BAT3 modulates p300-dependent acetylation of p53 and autophagy-related protein 7
      (ATG7) during autophagy.
AB  - Autophagy is regulated by posttranslational modifications, including acetylation.
      Here we show that HLA-B-associated transcript 3 (BAT3) is essential for basal and
      starvation-induced autophagy in embryonic day 18.5 BAT3(-/-) mouse embryos and in
      mouse embryonic fibroblasts (MEFs) through the modulation of p300-dependent
      acetylation of p53 and ATG7. Specifically, BAT3 increases p53 acetylation and
      proautophagic p53 target gene expression, while limiting p300-dependent
      acetylation of ATG7, a mechanism known to inhibit autophagy. In the absence of
      BAT3 or when BAT3 is located exclusively in the cytosol, autophagy is abrogated,
      ATG7 is hyperacetylated, p53 acetylation is abolished, and p300 accumulates in
      the cytosol, indicating that BAT3 regulates the nuclear localization of p300. In
      addition, the interaction between BAT3 and p300 is stronger in the cytosol than
      in the nucleus and, during starvation, the level of p300 decreases in the cytosol
      but increases in the nucleus only in the presence of BAT3. We conclude that BAT3
      tightly controls autophagy by modulating p300 intracellular localization,
      affecting the accessibility of p300 to its substrates, p53 and ATG7. 

PMID- 24591582
TI  - Holomorphic projections and Ramanujan's mock theta functions.
AB  - We use spectral methods of automorphic forms to establish a holomorphic
      projection operator for tensor products of vector-valued harmonic weak Maass
      forms and vector-valued modular forms. We apply this operator to discover simple
      recursions for Fourier series coefficients of Ramanujan's mock theta functions. 

PMID- 24591581
TI  - Transcriptional divergence and conservation of human and mouse erythropoiesis.
AB  - Mouse models have been used extensively for decades and have been instrumental in
      improving our understanding of mammalian erythropoiesis. Nonetheless, there are
      several examples of variation between human and mouse erythropoiesis. We
      performed a comparative global gene expression study using data from
      morphologically identical stage-matched sorted populations of human and mouse
      erythroid precursors from early to late erythroblasts. Induction and repression
      of major transcriptional regulators of erythropoiesis, as well as major erythroid
      important proteins, are largely conserved between the species. In contrast, at a
      global level we identified a significant extent of divergence between the
      species, both at comparable stages and in the transitions between stages,
      especially for the 500 most highly expressed genes during development. This
      suggests that the response of multiple developmentally regulated genes to key
      erythroid transcriptional regulators represents an important modification that
      has occurred in the course of erythroid evolution. In developing a systematic
      framework to understand and study conservation and divergence between human and
      mouse erythropoiesis, we show how mouse models can fail to mimic specific human
      diseases and provide predictions for translating findings from mouse models to
      potential therapies for human disease. 

PMID- 24591580
TI  - Sequential breakdown of 3-phosphorylated phosphoinositides is essential for the
      completion of macropinocytosis.
AB  - Macropinocytosis is a highly conserved endocytic process by which extracellular
      fluid and solutes are internalized into cells. Macropinocytosis starts with the
      formation of membrane ruffles at the plasma membrane and ends with their closure.
      The transient and sequential emergence of phosphoinositides PI(3,4,5)P3 and
      PI(3,4)P2 in the membrane ruffles is essential for macropinocytosis. By making
      use of information in the Caenorhabditis elegans mutants defective in fluid-phase
      endocytosis, we found that mammalian phosphoinositide phosphatase MTMR6 that
      dephosphorylates PI(3)P to PI, and its binding partner MTMR9, are required for
      macropinocytosis. INPP4B, which dephosphorylates PI(3,4)P2 to PI(3)P, was also
      found to be essential for macropinocytosis. These phosphatases operate after the
      formation of membrane ruffles to complete macropinocytosis. Finally, we showed
      that KCa3.1, a Ca(2+)-activated K(+) channel that is activated by PI(3)P, is
      required for macropinocytosis. We propose that the sequential breakdown of
      PI(3,4,5)P3 -> PI(3,4)P2 -> PI(3)P -> PI controls macropinocytosis through
      specific effectors of the intermediate phosphoinositides. 

PMID- 24591583
TI  - Hic-5 is a transcription coregulator that acts before and/or after glucocorticoid
      receptor genome occupancy in a gene-selective manner.
AB  - Ligand activation and DNA-binding dictate the outcome of glucocorticoid receptor
      (GR)-mediated transcriptional regulation by inducing diverse receptor
      conformations that interact differentially with coregulators. GR recruits many
      coregulators via the well-characterized AF2 interaction surface in the GR ligand
      binding domain, but Lin11, Isl-1, Mec-3 (LIM) domain coregulator Hic-5 (TGFB1I1)
      binds to the relatively uncharacterized tau2 activation domain in the hinge
      region of GR. Requirement of hydrogen peroxide-inducible clone-5 (Hic-5) for
      glucocorticoid-regulated gene expression was defined by Hic-5 depletion and
      global gene-expression analysis. Hic-5 depletion selectively affected both
      activation and repression of GR target genes, and Hic-5 served as an on/off
      switch for glucocorticoid regulation of many genes. For some hormone-induced
      genes, Hic-5 facilitated recruitment of Mediator complex. In contrast, many genes
      were not regulated by glucocorticoid until Hic-5 was depleted. On these genes Hic
      5 prevented GR occupancy and chromatin remodeling and thereby inhibited their
      hormone-dependent regulation. Transcription factor binding to genomic sites is
      highly variable among different cell types; Hic-5 represents an alternative
      mechanism for regulating transcription factor-binding site selection that could
      apply both within a given cell type and among different cell types. Thus, Hic-5
      is a versatile coregulator that acts by multiple gene-specific mechanisms that
      influence genomic occupancy of GR as well transcription complex assembly. 

PMID- 24591584
TI  - Concert halls with strong lateral reflections enhance musical dynamics.
AB  - One of the most thrilling cultural experiences is to hear live symphony-orchestra
      music build up from a whispering passage to a monumental fortissimo. The impact
      of such a crescendo has been thought to depend only on the musicians' skill, but
      here we show that interactions between the concert-hall acoustics and listeners'
      hearing also play a major role in musical dynamics. These interactions contribute
      to the shoebox-type concert hall's established success, but little prior research
      has been devoted to dynamic expression in this three-part transmission chain as a
      complete system. More forceful orchestral playing disproportionately excites high
      frequency harmonics more than those near the note's fundamental. This effect
      results in not only more sound energy, but also a different tone color. The
      concert hall transmits this sound, and the room geometry defines from which
      directions acoustic reflections arrive at the listener. Binaural directional
      hearing emphasizes high frequencies more when sound arrives from the sides of the
      head rather than from the median plane. Simultaneously, these same frequencies
      are emphasized by higher orchestral-playing dynamics. When the room geometry
      provides reflections from these directions, the perceived dynamic range is
      enhanced. Current room-acoustic evaluation methods assume linear behavior and
      thus neglect this effect. The hypothesis presented here is that the auditory
      excitation by reflections is emphasized with an orchestra forte most in concert
      halls with strong lateral reflections. The enhanced dynamic range provides an
      explanation for the success of rectangularly shaped concert-hall geometry. 

PMID- 24591585
TI  - Amazonian functional diversity from forest canopy chemical assembly.
AB  - Patterns of tropical forest functional diversity express processes of ecological
      assembly at multiple geographic scales and aid in predicting ecological responses
      to environmental change. Tree canopy chemistry underpins forest functional
      diversity, but the interactive role of phylogeny and environment in determining
      the chemical traits of tropical trees is poorly known. Collecting and analyzing
      foliage in 2,420 canopy tree species across 19 forests in the western Amazon, we
      discovered (i) systematic, community-scale shifts in average canopy chemical
      traits along gradients of elevation and soil fertility; (ii) strong phylogenetic
      partitioning of structural and defense chemicals within communities independent
      of variation in environmental conditions; and (iii) strong environmental control
      on foliar phosphorus and calcium, the two rock-derived elements limiting CO2
      uptake in tropical forests. These findings indicate that the chemical diversity
      of western Amazonian forests occurs in a regionally nested mosaic driven by long
      term chemical trait adjustment of communities to large-scale environmental
      filters, particularly soils and climate, and is supported by phylogenetic
      divergence of traits essential to foliar survival under varying environmental
      conditions. Geographically nested patterns of forest canopy chemical traits will
      play a role in determining the response and functional rearrangement of western
      Amazonian ecosystems to changing land use and climate. 

PMID- 24591586
TI  - A soil actinobacterium scavenges atmospheric H2 using two membrane-associated,
      oxygen-dependent [NiFe] hydrogenases.
AB  - In the Earth's lower atmosphere, H2 is maintained at trace concentrations (0.53
      ppmv/0.40 nM) and rapidly turned over (lifetime <= 2.1 y(-1)). It is thought that
      soil microbes, likely actinomycetes, serve as the main global sink for
      tropospheric H2. However, no study has ever unambiguously proven that a
      hydrogenase can oxidize this trace gas. In this work, we demonstrate, by using
      genetic dissection and sensitive GC measurements, that the soil actinomycete
      Mycobacterium smegmatis mc(2)155 constitutively oxidizes subtropospheric
      concentrations of H2. We show that two membrane-associated, oxygen-dependent
      [NiFe] hydrogenases mediate this process. Hydrogenase-1 (Hyd1) (MSMEG_2262-2263)
      is well-adapted to rapidly oxidize H2 at a range of concentrations [Vmax(app) =
      12 nmol?g?dw(-1)?min(-1); Km(app) = 180 nM; threshold = 130 pM in the Deltahyd23
      (Hyd1 only) strain], whereas Hyd2 (MSMEG_2719-2720) catalyzes a slower-acting,
      higher-affinity process [Vmax(app) = 2.5 nmol?g?dw(-1)?min(-1); Km(app) = 50 nM;
      threshold = 50 pM in the Deltahyd13 (Hyd2 only) strain]. These observations
      strongly support previous studies that have linked group 5 [NiFe] hydrogenases
      (e.g., Hyd2) to the oxidation of tropospheric H2 in soil ecosystems. We further
      reveal that group 2a [NiFe] hydrogenases (e.g., Hyd1) can contribute to this
      process. Hydrogenase expression and activity increases in carbon-limited cells,
      suggesting that scavenging of trace H2 helps to sustain dormancy. Distinct
      physiological roles for Hyd1 and Hyd2 during the adaptation to this condition are
      proposed. Soil organisms harboring high-affinity hydrogenases may be especially
      competitive, given that they harness a highly dependable fuel source in otherwise
      unstable environments. 

PMID- 24591587
TI  - Actin-dependent plastid movement is required for motive force generation in
      directional nuclear movement in plants.
AB  - Nuclear movement and positioning are indispensable for most cellular functions.
      In plants, strong light-induced chloroplast movement to the side walls of the
      cell is essential for minimizing damage from strong visible light. Strong light
      induced nuclear movement to the side walls also has been suggested to play an
      important role in minimizing damage from strong UV light. Although both movements
      are regulated by the same photoreceptor, phototropin, the precise cytoskeleton
      based force generation mechanism for nuclear movement is unknown, in contrast to
      the short actin-based mechanism of chloroplast movement. Here we show that actin
      dependent movement of plastids attached to the nucleus is essential for light
      induced nuclear movement in the Arabidopsis leaf epidermal cell. We found that
      nuclei are always associated with some plastids, and that light-induced nuclear
      movement is correlated with the dynamics of short actin filaments associated with
      plastids. Indeed, nuclei without plastid attachments do not exhibit blue light
      induced directional movement. Our results demonstrate that nuclei are incapable
      of autonomously moving in response to light, whereas attached plastids carry
      nuclei via the short actin filament-based movement. Thus, the close association
      between nuclei and plastids is essential for their cooperative movements and
      functions. 

PMID- 24591588
TI  - Marine fish may be biochemically constrained from inhabiting the deepest ocean
      depths.
AB  - No fish have been found in the deepest 25% of the ocean (8,400-11,000 m). This
      apparent absence has been attributed to hydrostatic pressure, although direct
      evidence is wanting because of the lack of deepest-living species to study. The
      common osmolyte trimethylamine N-oxide (TMAO) stabilizes proteins against
      pressure and increases with depth, going from 40 to 261 mmol/kg in teleost fishes
      from 0 to 4,850 m. TMAO accumulation with depth results in increasing internal
      osmolality (typically 350 mOsmol/kg in shallow species compared with seawater's
      1,100 mOsmol/kg). Preliminary extrapolation of osmolalities of predicted
      isosmotic state at 8,000-8,500 m may indicate a possible physiological limit, as
      greater depths would require reversal of osmotic gradients and, thus,
      osmoregulatory systems. We tested this prediction by capturing five of the second
      deepest known fish, the hadal snailfish (Notoliparis kermadecensis; Liparidae),
      from 7,000 m in the Kermadec Trench. We found their muscles to have a TMAO
      content of 386 +/- 18 mmol/kg and osmolality of 991 +/- 22 mOsmol/kg. These data
      fit previous extrapolations and, combined with new osmolalities from bathyal and
      abyssal fishes, predict isosmotic state at 8,200 m. This is previously
      unidentified evidence that biochemistry could constrain the depth of a large,
      complex taxonomic group. 

PMID- 24591589
TI  - Clioquinol promotes the degradation of metal-dependent amyloid-beta (Abeta)
      oligomers to restore endocytosis and ameliorate Abeta toxicity.
AB  - Alzheimer's disease (AD) is a common, progressive neurodegenerative disorder
      without effective disease-modifying therapies. The accumulation of amyloid-beta
      peptide (Abeta) is associated with AD. However, identifying new compounds that
      antagonize the underlying cellular pathologies caused by Abeta has been hindered
      by a lack of cellular models amenable to high-throughput chemical screening. To
      address this gap, we use a robust and scalable yeast model of Abeta toxicity
      where the Abeta peptide transits through the secretory and endocytic compartments
      as it does in neurons. The pathogenic Abeta 1-42 peptide forms more oligomers and
      is more toxic than Abeta 1-40 and genome-wide genetic screens identified genes
      that are known risk factors for AD. Here, we report an unbiased screen of
      ~140,000 compounds for rescue of Abeta toxicity. Of ~30 hits, several were 8
      hydroxyquinolines (8-OHQs). Clioquinol (CQ), an 8-OHQ previously reported to
      reduce Abeta burden, restore metal homeostasis, and improve cognition in mouse AD
      models, was also effective and rescued the toxicity of Abeta secreted from
      glutamatergic neurons in Caenorhabditis elegans. In yeast, CQ dramatically
      reduced Abeta peptide levels in a copper-dependent manner by increasing
      degradation, ultimately restoring endocytic function. This mirrored its effects
      on copper-dependent oligomer formation in vitro, which was also reversed by CQ.
      This unbiased screen indicates that copper-dependent Abeta oligomer formation
      contributes to Abeta toxicity within the secretory/endosomal pathways where it
      can be targeted with selective metal binding compounds. Establishing the ability
      of the Abeta yeast model to identify disease-relevant compounds supports its
      further exploitation as a validated early discovery platform. 

PMID- 24591590
TI  - Thirty-thousand-year-old distant relative of giant icosahedral DNA viruses with a
      pandoravirus morphology.
AB  - The largest known DNA viruses infect Acanthamoeba and belong to two markedly
      different families. The Megaviridae exhibit pseudo-icosahedral virions up to 0.7
      MUm in diameter and adenine-thymine (AT)-rich genomes of up to 1.25 Mb encoding a
      thousand proteins. Like their Mimivirus prototype discovered 10 y ago, they
      entirely replicate within cytoplasmic virion factories. In contrast, the recently
      discovered Pandoraviruses exhibit larger amphora-shaped virions 1 MUm in length
      and guanine-cytosine-rich genomes up to 2.8 Mb long encoding up to 2,500
      proteins. Their replication involves the host nucleus. Whereas the Megaviridae
      share some general features with the previously described icosahedral large DNA
      viruses, the Pandoraviruses appear unrelated to them. Here we report the
      discovery of a third type of giant virus combining an even larger pandoravirus
      like particle 1.5 MUm in length with a surprisingly smaller 600 kb AT-rich
      genome, a gene content more similar to Iridoviruses and Marseillevirus, and a
      fully cytoplasmic replication reminiscent of the Megaviridae. This suggests that
      pandoravirus-like particles may be associated with a variety of virus families
      more diverse than previously envisioned. This giant virus, named Pithovirus
      sibericum, was isolated from a >30,000-y-old radiocarbon-dated sample when we
      initiated a survey of the virome of Siberian permafrost. The revival of such an
      ancestral amoeba-infecting virus used as a safe indicator of the possible
      presence of pathogenic DNA viruses, suggests that the thawing of permafrost
      either from global warming or industrial exploitation of circumpolar regions
      might not be exempt from future threats to human or animal health. 

PMID- 24591591
TI  - Individual letters of the RNA polymerase II CTD code govern distinct gene
      expression programs in fission yeast.
AB  - The primary structure and phosphorylation pattern of the tandem
      Y(1)S(2)P(3)T(4)S(5)P(6)S(7) repeats of the RNA polymerase II carboxyl-terminal
      domain (CTD) comprise an informational code that coordinates transcription,
      chromatin modification, and RNA processing. To gauge the contributions of
      individual CTD coding "letters" to gene expression, we analyzed the poly(A)(+)
      transcriptomes of fission yeast mutants that lack each of the four inessential
      CTD phosphoacceptors: Tyr1, Ser2, Thr4, and Ser7. There was a hierarchy of CTD
      mutational effects with respect to the number of dysregulated protein-coding
      RNAs, with S2A (n = 227) >> Y1F (n = 71) > S7A (n = 58) >> T4A (n = 7). The
      majority of the protein-coding RNAs affected in Y1F cells were coordinately
      affected by S2A, suggesting that Tyr1-Ser2 constitutes a two-letter code "word."
      Y1F and S2A elicited increased expression of genes encoding proteins involved in
      iron uptake (Frp1, Fip1, Fio1, Str3, Str1, Sib1), without affecting the
      expression of the genes that repress the iron regulon, implying that Tyr1-Ser2
      transduces a repressive signal. Y1F and S2A cells had increased levels of ferric
      reductase activity and were hypersensitive to phleomycin, indicative of elevated
      intracellular iron. The T4A and S7A mutations had opposing effects on the
      phosphate response pathway. T4A reduced the expression of two genes encoding
      proteins involved in phosphate acquisition (the Pho1 acid phosphatase and the
      phosphate transporter SPBC8E4.01c), without affecting the expression of known
      genes that regulate the phosphate response pathway, whereas S7A increased pho1(+)
      expression. These results highlight specific cellular gene expression programs
      that are responsive to distinct CTD cues. 

PMID- 24591592
TI  - Sparkling feather reflections of a bird-of-paradise explained by finite
      difference time-domain modeling.
AB  - Birds-of-paradise are nature's prime examples of the evolution of color by sexual
      selection. Their brilliant, structurally colored feathers play a principal role
      in mating displays. The structural coloration of both the occipital and breast
      feathers of the bird-of-paradise Lawes' parotia is produced by melanin rodlets
      arranged in layers, together acting as interference reflectors. Light reflection
      by the silvery colored occipital feathers is unidirectional as in a classical
      multilayer, but the reflection by the richly colored breast feathers is three
      directional and extraordinarily complex. Here we show that the reflection
      properties of both feather types can be quantitatively explained by finite
      difference time-domain modeling using realistic feather anatomies and
      experimentally determined refractive index dispersion values of keratin and
      melanin. The results elucidate the interplay between avian coloration and vision
      and indicate tuning of the mating displays to the spectral properties of the
      avian visual system. 

PMID- 24591593
TI  - Blood-spinal cord barrier disruption contributes to early motor-neuron
      degeneration in ALS-model mice.
AB  - Humans with ALS and transgenic rodents expressing ALS-associated superoxide
      dismutase (SOD1) mutations develop spontaneous blood-spinal cord barrier (BSCB)
      breakdown, causing microvascular spinal-cord lesions. The role of BSCB breakdown
      in ALS disease pathogenesis in humans and mice remains, however, unclear,
      although chronic blood-brain barrier opening has been shown to facilitate
      accumulation of toxic blood-derived products in the central nervous system,
      resulting in secondary neurodegenerative changes. By repairing the BSCB and/or
      removing the BSCB-derived injurious stimuli, we now identify that accumulation of
      blood-derived neurotoxic hemoglobin and iron in the spinal cord leads to early
      motor-neuron degeneration in SOD1(G93A) mice at least in part through iron
      dependent oxidant stress. Using spontaneous or warfarin-accelerated microvascular
      lesions, motor-neuron dysfunction and injury were found to be proportional to the
      degree of BSCB disruption at early disease stages in SOD1(G93A) mice. Early
      treatment with an activated protein C analog restored BSCB integrity that
      developed from spontaneous or warfarin-accelerated microvascular lesions in
      SOD1(G93A) mice and eliminated neurotoxic hemoglobin and iron deposits.
      Restoration of BSCB integrity delayed onset of motor-neuron impairment and
      degeneration. Early chelation of blood-derived iron and antioxidant treatment
      mitigated early motor-neuronal injury. Our data suggest that BSCB breakdown
      contributes to early motor-neuron degeneration in ALS mice and that restoring
      BSCB integrity during an early disease phase retards the disease process. 

PMID- 24591594
TI  - Ena/VASP Enabled is a highly processive actin polymerase tailored to self
      assemble parallel-bundled F-actin networks with Fascin.
AB  - Filopodia are exploratory finger-like projections composed of multiple long,
      straight, parallel-bundled actin filaments that protrude from the leading edge of
      migrating cells. Drosophila melanogaster Enabled (Ena) is a member of the
      Ena/vasodilator-stimulated phosphoprotein protein family, which facilitates the
      assembly of filopodial actin filaments that are bundled by Fascin. However, the
      mechanism by which Ena and Fascin promote the assembly of uniformly thick F-actin
      bundles that are capable of producing coordinated protrusive forces without
      buckling is not well understood. We used multicolor evanescent wave fluorescence
      microscopy imaging to follow individual Ena molecules on both single and Fascin
      bundled F-actin in vitro. Individual Ena tetramers increase the elongation rate
      approximately two- to threefold and inhibit capping protein by remaining
      processively associated with the barbed end for an average of ~10 s in solution,
      for ~60 s when immobilized on a surface, and for ~110 s when multiple Ena
      tetramers are clustered on a surface. Ena also can gather and simultaneously
      elongate multiple barbed ends. Collectively, these properties could facilitate
      the recruitment of Fascin and initiate filopodia formation. Remarkably, we found
      that Ena's actin-assembly properties are tunable on Fascin-bundled filaments,
      facilitating the formation of filopodia-like F-actin networks without tapered
      barbed ends. Ena-associated trailing barbed ends in Fascin-bundled actin
      filaments have approximately twofold more frequent and approximately fivefold
      longer processive runs, allowing them to catch up with leading barbed ends
      efficiently. Therefore, Fascin and Ena cooperate to extend and maintain robust
      filopodia of uniform thickness with aligned barbed ends by a unique mechanistic
      cycle. 

PMID- 24591595
TI  - Identifying the macromolecular targets of de novo-designed chemical entities
      through self-organizing map consensus.
AB  - De novo molecular design and in silico prediction of polypharmacological profiles
      are emerging research topics that will profoundly affect the future of drug
      discovery and chemical biology. The goal is to identify the macromolecular
      targets of new chemical agents. Although several computational tools for
      predicting such targets are publicly available, none of these methods was
      explicitly designed to predict target engagement by de novo-designed molecules.
      Here we present the development and practical application of a unique technique,
      self-organizing map-based prediction of drug equivalence relationships (SPiDER),
      that merges the concepts of self-organizing maps, consensus scoring, and
      statistical analysis to successfully identify targets for both known drugs and
      computer-generated molecular scaffolds. We discovered a potential off-target
      liability of fenofibrate-related compounds, and in a comprehensive prospective
      application, we identified a multitarget-modulating profile of de novo designed
      molecules. These results demonstrate that SPiDER may be used to identify
      innovative compounds in chemical biology and in the early stages of drug
      discovery, and help investigate the potential side effects of drugs and their
      repurposing options. 

PMID- 24591596
TI  - Anisotropic two-dimensional electron gas at SrTiO3(110).
AB  - Two-dimensional electron gases (2DEGs) at oxide heterostructures are attracting
      considerable attention, as these might one day substitute conventional
      semiconductors at least for some functionalities. Here we present a minimal setup
      for such a 2DEG--the SrTiO3(110)-(4 * 1) surface, natively terminated with one
      monolayer of tetrahedrally coordinated titania. Oxygen vacancies induced by
      synchrotron radiation migrate underneath this overlayer; this leads to a
      confining potential and electron doping such that a 2DEG develops. Our angle
      resolved photoemission spectroscopy and theoretical results show that confinement
      along (110) is strikingly different from the (001) crystal orientation. In
      particular, the quantized subbands show a surprising "semiheavy" band, in
      contrast with the analog in the bulk, and a high electronic anisotropy. This
      anisotropy and even the effective mass of the (110) 2DEG is tunable by doping,
      offering a high flexibility to engineer the properties of this system. 

PMID- 24591597
TI  - Strength of a bifurcated H bond.
AB  - Macromolecules are characterized by their particular arrangement of H bonds. Many
      of these interactions involve a single donor and acceptor pair, such as the
      regular H-bonding pattern between carbonyl oxygens and amide H(+)s four residues
      apart in alpha-helices. The H-bonding potential of some acceptors, however, leads
      to the phenomenon of overcoordination between two donors and one acceptor.
      Herein, using isotope-edited Fourier transform infrared measurements and density
      functional theory (DFT) calculations, we measured the strength of such bifurcated
      H bonds in a transmembrane alpha-helix. Frequency shifts of the (13)C=(18)O amide
      I mode were used as a reporter of the strength of the bifurcated H bond from a
      thiol and hydroxyl H(+) at residue i + 4. DFT calculations yielded very similar
      frequency shifts and an energy of -2.6 and -3.4 kcal/mol for the thiol and
      hydroxyl bifurcated H bonds, respectively. The strength of the intrahelical
      bifurcated H bond is consistent with its prevalence in hydrophobic environments
      and is shown to significantly impact side-chain rotamer distribution. 

PMID- 24591598
TI  - Electric double-layer transistor using layered iron selenide Mott insulator
      TlFe1.6Se2.
AB  - A(1-x)Fe(2-y)Se2 (A = K, Cs, Rb, Tl) are recently discovered iron-based
      superconductors with critical temperatures (Tc) ranging up to 32 K. Their parent
      phases have unique properties compared with other iron-based superconductors;
      e.g., their crystal structures include ordered Fe vacancies, their normal states
      are antiferromagnetic (AFM) insulating phases, and they have extremely high Neel
      transition temperatures. However, control of carrier doping into the parent AFM
      insulators has been difficult due to their intrinsic phase separation. Here, we
      fabricated an Fe-vacancy-ordered TlFe1.6Se2 insulating epitaxial film with an
      atomically flat surface and examined its electrostatic carrier doping using an
      electric double-layer transistor (EDLT) structure with an ionic liquid gate. The
      positive gate voltage gave a conductance modulation of three orders of magnitude
      at 25 K, and further induced and manipulated a phase transition; i.e.,
      delocalized carrier generation by electrostatic doping is the origin of the phase
      transition. This is the first demonstration, to the authors' knowledge, of an
      EDLT using a Mott insulator iron selenide channel and opens a way to explore high
      Tc superconductivity in iron-based layered materials, where carrier doping by
      conventional chemical means is difficult.

PMID- 24591599
TI  - Two distinct neural mechanisms underlying indirect reciprocity.
AB  - Cooperation is a hallmark of human society. Humans often cooperate with strangers
      even if they will not meet each other again. This so-called indirect reciprocity
      enables large-scale cooperation among nonkin and can occur based on a reputation
      mechanism or as a succession of pay-it-forward behavior. Here, we provide the
      functional and anatomical neural evidence for two distinct mechanisms governing
      the two types of indirect reciprocity. Cooperation occurring as reputation-based
      reciprocity specifically recruited the precuneus, a region associated with self
      centered cognition. During such cooperative behavior, the precuneus was
      functionally connected with the caudate, a region linking rewards to behavior.
      Furthermore, the precuneus of a cooperative subject had a strong resting-state
      functional connectivity (rsFC) with the caudate and a large gray matter volume.
      In contrast, pay-it-forward reciprocity recruited the anterior insula (AI), a
      brain region associated with affective empathy. The AI was functionally connected
      with the caudate during cooperation occurring as pay-it-forward reciprocity, and
      its gray matter volume and rsFC with the caudate predicted the tendency of such
      cooperation. The revealed difference is consistent with the existing results of
      evolutionary game theory: although reputation-based indirect reciprocity robustly
      evolves as a self-interested behavior in theory, pay-it-forward indirect
      reciprocity does not on its own. The present study provides neural mechanisms
      underlying indirect reciprocity and suggests that pay-it-forward reciprocity may
      not occur as myopic profit maximization but elicit emotional rewards. 

PMID- 24591600
TI  - Fatty acid-inducible ANGPTL4 governs lipid metabolic response to exercise.
AB  - Physical activity increases energy metabolism in exercising muscle. Whether acute
      exercise elicits metabolic changes in nonexercising muscles remains unclear. We
      show that one of the few genes that is more highly induced in nonexercising
      muscle than in exercising human muscle during acute exercise encodes angiopoietin
      like 4 (ANGPTL4), an inhibitor of lipoprotein lipase-mediated plasma triglyceride
      clearance. Using a combination of human, animal, and in vitro data, we show that
      induction of ANGPTL4 in nonexercising muscle is mediated by elevated plasma free
      fatty acids via peroxisome proliferator-activated receptor-delta, presumably
      leading to reduced local uptake of plasma triglyceride-derived fatty acids and
      their sparing for use by exercising muscle. In contrast, the induction of ANGPTL4
      in exercising muscle likely is counteracted via AMP-activated protein kinase
      (AMPK)-mediated down-regulation, promoting the use of plasma triglycerides as
      fuel for active muscles. Our data suggest that nonexercising muscle and the local
      regulation of ANGPTL4 via AMPK and free fatty acids have key roles in governing
      lipid homeostasis during exercise. 

PMID- 24591602
TI  - Categorical encoding of color in the brain.
AB  - The areas of the brain that encode color categorically have not yet been reliably
      identified. Here, we used functional MRI adaptation to identify neuronal
      populations that represent color categories irrespective of metric differences in
      color. Two colors were successively presented within a block of trials. The two
      colors were either from the same or different categories (e.g., "blue 1 and blue
      2" or "blue 1 and green 1"), and the size of the hue difference was varied.
      Participants performed a target detection task unrelated to the difference in
      color. In the middle frontal gyrus of both hemispheres and to a lesser extent,
      the cerebellum, blood-oxygen level-dependent response was greater for colors from
      different categories relative to colors from the same category. Importantly,
      activation in these regions was not modulated by the size of the hue difference,
      suggesting that neurons in these regions represent color categorically,
      regardless of metric color difference. Representational similarity analyses,
      which investigated the similarity of the pattern of activity across local groups
      of voxels, identified other regions of the brain (including the visual cortex),
      which responded to metric but not categorical color differences. Therefore,
      categorical and metric hue differences appear to be coded in qualitatively
      different ways and in different brain regions. These findings have implications
      for the long-standing debate on the origin and nature of color categories, and
      also further our understanding of how color is processed by the brain. 

PMID- 24591601
TI  - Activation induced deaminase C-terminal domain links DNA breaks to end protection
      and repair during class switch recombination.
AB  - Activation-induced deaminase (AID) triggers antibody class switch recombination
      (CSR) in B cells by initiating DNA double strand breaks that are repaired by
      nonhomologous end-joining pathways. A role for AID at the repair step is unclear.
      We show that specific inactivation of the C-terminal AID domain encoded by exon 5
      (E5) allows very efficient deamination of the AID target regions but greatly
      impacts the efficiency and quality of subsequent DNA repair. Specifically
      eliminating E5 not only precludes CSR but also, causes an atypical, enzymatic
      activity-dependent dominant-negative effect on CSR. Moreover, the E5 domain is
      required for the formation of AID-dependent Igh-cMyc chromosomal translocations.
      DNA breaks at the Igh switch regions induced by AID lacking E5 display defective
      end joining, failing to recruit DNA damage response factors and undergoing
      extensive end resection. These defects lead to nonproductive resolutions, such as
      rearrangements and homologous recombination that can antagonize CSR. Our results
      can explain the autosomal dominant inheritance of AID variants with truncated E5
      in patients with hyper-IgM syndrome 2 and establish that AID, through the E5
      domain, provides a link between DNA damage and repair during CSR. 

PMID- 24591603
TI  - Real-time analysis of composite magnetic nanoparticle disassembly in vascular
      cells and biomimetic media.
AB  - The fate of nanoparticle (NP) formulations in the multifaceted biological
      environment is a key determinant of their biocompatibility and therapeutic
      performance. An understanding of the degradation patterns of different types of
      clinically used and experimental NP formulations is currently incomplete, posing
      an unmet need for novel analytical tools providing unbiased quantitative
      measurements of NP disassembly directly in the medium of interest and in
      conditions relevant to specific therapeutic/diagnostic applications. In the
      present study, this challenge was addressed with an approach enabling real-time
      in situ monitoring of the integrity status of NPs in cells and biomimetic media
      using Forster resonance energy transfer (FRET). Disassembly of polylactide-based
      magnetic NPs (MNPs) was investigated in a range of model biomimetic media and in
      cultured vascular cells using an experimentally established quantitative
      correlation between particle integrity and FRET efficiency controlled through
      adjustments in the spectral overlap between two custom-synthesized polylactide
      fluorophore (boron dipyrromethene) conjugates incorporated in MNPs. The results
      suggest particle disassembly governed by diffusion-reaction processes with
      kinetics strongly dependent on conditions promoting release of oligomeric
      fragments from the particle matrix. Thus, incubation in gels simulating the
      extracellular environment and in protein-rich serum resulted in notably lower and
      higher MNP decomposition rates, respectively, compared with nonviscous liquid
      buffers. The diffusion-reaction mechanism also is consistent with a significant
      cell growth-dependent acceleration of MNP processing in dividing vs. contact
      inhibited vascular cells. The FRET-based analytical strategy and experimental
      results reported herein may facilitate the development and inform optimization of
      biodegradable nanocarriers for cell and drug delivery applications. 

PMID- 24591604
TI  - Harvesting renewable energy from Earth's mid-infrared emissions.
AB  - It is possible to harvest energy from Earth's thermal infrared emission into
      outer space. We calculate the thermodynamic limit for the amount of power
      available, and as a case study, we plot how this limit varies daily and
      seasonally in a location in Oklahoma. We discuss two possible ways to make such
      an emissive energy harvester (EEH): A thermal EEH (analogous to solar thermal
      power generation) and an optoelectronic EEH (analogous to photovoltaic power
      generation). For the latter, we propose using an infrared-frequency rectifying
      antenna, and we discuss its operating principles, efficiency limits, system
      design considerations, and possible technological implementations. 

PMID- 24591605
TI  - Small molecule probes to quantify the functional fraction of a specific protein
      in a cell with minimal folding equilibrium shifts.
AB  - Although much is known about protein folding in buffers, it remains unclear how
      the cellular protein homeostasis network functions as a system to partition
      client proteins between folded and functional, soluble and misfolded, and
      aggregated conformations. Herein, we develop small molecule folding probes that
      specifically react with the folded and functional fraction of the protein of
      interest, enabling fluorescence-based quantification of this fraction in cell
      lysate at a time point of interest. Importantly, these probes minimally perturb a
      protein's folding equilibria within cells during and after cell lysis, because
      sufficient cellular chaperone/chaperonin holdase activity is created by rapid ATP
      depletion during cell lysis. The folding probe strategy and the faithful
      quantification of a particular protein's functional fraction are exemplified with
      retroaldolase, a de novo designed enzyme, and transthyretin, a nonenzyme protein.
      Our findings challenge the often invoked assumption that the soluble fraction of
      a client protein is fully folded in the cell. Moreover, our results reveal that
      the partitioning of destabilized retroaldolase and transthyretin mutants between
      the aforementioned conformational states is strongly influenced by cytosolic
      proteostasis network perturbations. Overall, our results suggest that applying a
      chemical folding probe strategy to other client proteins offers opportunities to
      reveal how the proteostasis network functions as a system to regulate the folding
      and function of individual client proteins in vivo. 

PMID- 24591606
TI  - Single-molecule studies of polymerase dynamics and stoichiometry at the
      bacteriophage T7 replication machinery.
AB  - Replication of DNA plays a central role in transmitting hereditary information
      from cell to cell. To achieve reliable DNA replication, multiple proteins form a
      stable complex, known as the replisome, enabling them to act together in a highly
      coordinated fashion. Over the past decade, the roles of the various proteins
      within the replisome have been determined. Although many of their interactions
      have been characterized, it remains poorly understood how replication proteins
      enter and leave the replisome. In this study, we visualize fluorescently labeled
      bacteriophage T7 DNA polymerases within the replisome while we simultaneously
      observe the kinetics of the replication process. This combination of observables
      allows us to monitor both the activity and dynamics of individual polymerases
      during coordinated leading- and lagging-strand synthesis. Our data suggest that
      lagging-strand polymerases are exchanged at a frequency similar to that of
      Okazaki fragment synthesis and that two or more polymerases are present in the
      replisome during DNA replication. Our studies imply a highly dynamic picture of
      the replisome with lagging-strand DNA polymerases residing at the fork for the
      synthesis of only a few Okazaki fragments. Further, new lagging-strand
      polymerases are readily recruited from a pool of polymerases that are proximally
      bound to the replisome and continuously replenished from solution. 

PMID- 24591607
TI  - Evidence that dimethyl sulfide facilitates a tritrophic mutualism between marine
      primary producers and top predators.
AB  - Tritrophic mutualistic interactions have been best studied in plant-insect
      systems. During these interactions, plants release volatiles in response to
      herbivore damage, which, in turn, facilitates predation on primary consumers or
      benefits the primary producer by providing nutrients. Here we explore a similar
      interaction in the Southern Ocean food web, where soluble iron limits primary
      productivity. Dimethyl sulfide has been studied in the context of global climate
      regulation and is an established foraging cue for marine top predators. We
      present evidence that procellariiform seabird species that use dimethyl sulfide
      as a foraging cue selectively forage on phytoplankton grazers. Their contribution
      of beneficial iron recycled to marine phytoplankton via excretion suggests a
      chemically mediated link between marine top predators and oceanic primary
      production. 

PMID- 24591608
TI  - Perceptions of water use.
AB  - In a national online survey, 1,020 participants reported their perceptions of
      water use for household activities. When asked for the most effective strategy
      they could implement to conserve water in their lives, or what other Americans
      could do, most participants mentioned curtailment (e.g., taking shorter showers,
      turning off the water while brushing teeth) rather than efficiency improvements
      (e.g., replacing toilets, retrofitting washers). This contrasts with expert
      recommendations. Additionally, some participants are more likely to list
      curtailment actions for themselves, but list efficiency actions for other
      Americans. For a sample of 17 activities, participants underestimated water use
      by a factor of 2 on average, with large underestimates for high water-use
      activities. An additional ranking task showed poor discrimination of low vs. high
      embodied water content in food products. High numeracy scores, older age, and
      male sex were associated with more accurate perceptions of water use. Overall,
      perception of water use is more accurate than the perception of energy
      consumption and savings previously reported. Well-designed efforts to improve
      public understanding of household water use could pay large dividends for
      behavioral adaptation to temporary or long-term decreases in availability of
      fresh water. 

PMID- 24591609
TI  - Disease causing mutants of TDP-43 nucleic acid binding domains are resistant to
      aggregation and have increased stability and half-life.
AB  - Over the last two decades many secrets of the age-related human neural
      proteinopathies have been revealed. A common feature of these diseases is
      abnormal, and possibly pathogenic, aggregation of specific proteins in the
      effected tissue often resulting from inherent or decreased structural stability.
      An archetype example of this is superoxide dismutase-1, the first genetic factor
      to be linked with amyotrophic lateral sclerosis (ALS). Mutant or
      posttranslationally modified TAR DNA binding protein-32 (TDP-43) is also strongly
      associated with ALS and an increasingly large number of other neurodegenerative
      diseases, including frontotemporal lobar degeneration (FTLD). Cytoplasmic
      mislocalization and elevated half-life is a characteristic of mutant TDP-43.
      Furthermore, patient age at the onset of disease symptoms shows a good inverse
      correlation with mutant TDP-43 half-life. Here we show that ALS and FTLD
      associated TDP-43 mutations in the central nucleic acid binding domains lead to
      elevated half-life and this is commensurate with increased thermal stability and
      inhibition of aggregation. It is achieved without impact on secondary, tertiary,
      or quaternary structure. We propose that tighter structural cohesion contributes
      to reduced protein turnover, increasingly abnormal proteostasis and, ultimately,
      faster onset of disease symptoms. These results contrast our perception of
      neurodegenerative diseases as misfolded proteinopathies and delineate a novel
      path from the molecular characteristics of mutant TDP-43 to aberrant cellular
      effects and patient phenotype. 

PMID- 24591610
TI  - Memory loss in a nonnavigational spatial task after hippocampal inactivation in
      monkeys.
AB  - The hippocampus has a well-documented role for spatial navigation across species,
      but its role for spatial memory in nonnavigational tasks is uncertain. In
      particular, when monkeys are tested in tasks that do not require navigation,
      spatial memory seems unaffected by lesions of the hippocampus. However, the
      interpretation of these results is compromised by long-term compensatory
      adaptation occurring in the days and weeks after lesions. To test the hypothesis
      that hippocampus is necessary for nonnavigational spatial memory, we selected a
      technique that avoids long-term compensatory adaptation. We transiently disrupted
      hippocampal function acutely at the time of testing by microinfusion of the
      glutamate receptor antagonist kynurenate. Animals were tested on a self-ordered
      spatial memory task, the Hamilton Search Task. In the task, animals are presented
      with an array of eight boxes, each containing a food reinforcer; one box may be
      opened per trial, with trials separated by a delay. Only the spatial location of
      the boxes serves as a cue to solve the task. The optimal strategy is to open each
      box once without returning to previously visited locations. Transient
      inactivation of hippocampus reduced performance to chance levels in a delay
      dependent manner. In contrast, no deficits were seen when boxes were marked with
      nonspatial cues (color). These results clearly document a role for hippocampus in
      nonnavigational spatial memory in macaques and demonstrate the efficacy of
      pharmacological inactivation of this structure in this species. Our data bring
      the role of the hippocampus in monkeys into alignment with the broader framework
      of hippocampal function. 

PMID- 24591611
TI  - Quantifying the atomic-level mechanics of single long physisorbed molecular
      chains.
AB  - Individual in situ polymerized fluorene chains 10-100 nm long linked by C-C bonds
      are pulled vertically from an Au(111) substrate by the tip of a low-temperature
      atomic force microscope. The conformation of the selected chains is imaged before
      and after manipulation using scanning tunneling microscopy. The measured force
      gradient shows strong and periodic variations that correspond to the step-by-step
      detachment of individual fluorene repeat units. These variations persist at
      constant intensity until the entire polymer is completely removed from the
      surface. Calculations based on an extended Frenkel-Kontorova model reproduce the
      periodicity and magnitude of these features and allow us to relate them to the
      detachment force and desorption energy of the repeat units. The adsorbed part of
      the polymer slides easily along the surface during the pulling process, leading
      to only small oscillations as a result of the high stiffness of the fluorenes and
      of their length mismatch with respect to the substrate surface structure. A
      significant lateral force also is caused by the sequential detachment of
      individual units. The gained insight into the molecule-surface interactions
      during sliding and pulling should aid the design of mechanoresponsive nanosystems
      and devices. 

PMID- 24591612
TI  - Collective dynamics of stem cell populations.

PMID- 24591613
TI  - A controlling role for the air-sea interface in the chemical processing of
      reactive nitrogen in the coastal marine boundary layer.
AB  - The lifetime of reactive nitrogen and the production rate of reactive halogens in
      the marine boundary layer are strongly impacted by reactions occurring at aqueous
      interfaces. Despite the potential importance of the air-sea interface in serving
      as a reactive surface, few direct field observations are available to assess its
      impact on reactive nitrogen deposition and halogen activation. Here, we present
      direct measurements of the vertical fluxes of the reactant-product pair N2O5 and
      ClNO2 to assess the role of the ocean surface in the exchange of reactive
      nitrogen and halogens. We measure nocturnal N2O5 exchange velocities (Vex = -1.66
      +/- 0.60 cm s(-1)) that are limited by atmospheric transport of N2O5 to the air
      sea interface. Surprisingly, vertical fluxes of ClNO2, the product of N2O5
      reactive uptake to concentrated chloride containing surfaces, display net
      deposition, suggesting that elevated ClNO2 mixing ratios found in the marine
      boundary layer are sustained primarily by N2O5 reactions with aerosol particles.
      Comparison of measured deposition rates and in situ observations of N2O5 reactive
      uptake to aerosol particles indicates that N2O5 deposition to the ocean surface
      accounts for between 26% and 42% of the total loss rate. The combination of large
      Vex, N2O5 and net deposition of ClNO2 acts to limit NOx recycling rates and the
      production of Cl atoms by shortening the nocturnal lifetime of N2O5. These
      results indicate that air-sea exchange processes account for as much as 15% of
      nocturnal NOx removal in polluted coastal regions and can serve to reduce ClNO2
      concentrations at sunrise by over 20%. 

PMID- 24591615
TI  - Graph-based sampling for approximating global helical topologies of RNA.
AB  - A current challenge in RNA structure prediction is the description of global
      helical arrangements compatible with a given secondary structure. Here we address
      this problem by developing a hierarchical graph sampling/data mining approach to
      reduce conformational space and accelerate global sampling of candidate
      topologies. Starting from a 2D structure, we construct an initial graph from size
      measures deduced from solved RNAs and junction topologies predicted by our data
      mining algorithm RNAJAG trained on known RNAs. We sample these graphs in 3D space
      guided by knowledge-based statistical potentials derived from bending and torsion
      measures of internal loops as well as radii of gyration for known RNAs. Graph
      sampling results for 30 representative RNAs are analyzed and compared with
      reference graphs from both solved structures and predicted structures by
      available programs. This comparison indicates promise for our graph-based
      sampling approach for characterizing global helical arrangements in large RNAs:
      graph rmsds range from 2.52 to 28.24 A for RNAs of size 25-158 nucleotides, and
      more than half of our graph predictions improve upon other programs. The
      efficiency in graph sampling, however, implies an additional step of translating
      candidate graphs into atomic models. Such models can be built with the same idea
      of graph partitioning and build-up procedures we used for RNA design. 

PMID- 24591614
TI  - Four-dimensional live imaging of apical biosynthetic trafficking reveals a post
      Golgi sorting role of apical endosomal intermediates.
AB  - Emerging data suggest that in polarized epithelial cells newly synthesized apical
      and basolateral plasma membrane proteins traffic through different endosomal
      compartments en route to the respective cell surface. However, direct evidence
      for trans-endosomal pathways of plasma membrane proteins is still missing and the
      mechanisms involved are poorly understood. Here, we imaged the entire
      biosynthetic route of rhodopsin-GFP, an apical marker in epithelial cells,
      synchronized through recombinant conditional aggregation domains, in live Madin
      Darby canine kidney cells using spinning disk confocal microscopy. Our
      experiments directly demonstrate that rhodopsin-GFP traffics through apical
      recycling endosomes (AREs) that bear the small GTPase Rab11a before arriving at
      the apical membrane. Expression of dominant-negative Rab11a drastically reduced
      apical delivery of rhodopsin-GFP and caused its missorting to the basolateral
      membrane. Surprisingly, functional inhibition of dynamin-2 trapped rhodopsin-GFP
      at AREs and caused aberrant accumulation of coated vesicles on AREs, suggesting a
      previously unrecognized role for dynamin-2 in the scission of apical carrier
      vesicles from AREs. A second set of experiments, using a unique method to carry
      out total internal reflection fluorescence microscopy (TIRFM) from the apical
      side, allowed us to visualize the fusion of rhodopsin-GFP carrier vesicles, which
      occurred randomly all over the apical plasma membrane. Furthermore, two-color
      TIRFM showed that Rab11a-mCherry was present in rhodopsin-GFP carrier vesicles
      and was rapidly released upon fusion onset. Our results provide direct evidence
      for a role of AREs as a post-Golgi sorting hub in the biosynthetic route of
      polarized epithelia, with Rab11a regulating cargo sorting at AREs and carrier
      vesicle docking at the apical membrane. 

PMID- 24591616
TI  - Seminal vesicle protein SVS2 is required for sperm survival in the uterus.
AB  - In mammals, sperm migrate through the female reproductive tract to reach the egg;
      however, our understanding of this journey is highly limited. To shed light on
      this process, we focused on defining the functions of seminal vesicle secretion 2
      (SVS2). SVS2(-/-) male mice produced sperm but were severely subfertile, and
      formation of a copulatory plug to cover the female genital opening did not occur.
      Surprisingly, even when artificial insemination was performed with silicon as a
      substitute for the plug, sperm fertility in the absence of SVS2 remained severely
      reduced because the sperm were already dead in the uterus. Thus, our results
      provide evidence that the uterus induces sperm cell death and that SVS2 protects
      sperm from uterine attack. 

PMID- 24591617
TI  - Carnitine metabolism to trimethylamine by an unusual Rieske-type oxygenase from
      human microbiota.
AB  - Dietary intake of L-carnitine can promote cardiovascular diseases in humans
      through microbial production of trimethylamine (TMA) and its subsequent oxidation
      to trimethylamine N-oxide by hepatic flavin-containing monooxygenases. Although
      our microbiota are responsible for TMA formation from carnitine, the underpinning
      molecular and biochemical mechanisms remain unclear. In this study, using
      bioinformatics approaches, we first identified a two-component Rieske-type
      oxygenase/reductase (CntAB) and associated gene cluster proposed to be involved
      in carnitine metabolism in representative genomes of the human microbiota. CntA
      belongs to a group of previously uncharacterized Rieske-type proteins and has an
      unusual "bridging" glutamate but not the aspartate residue, which is believed to
      facilitate intersubunit electron transfer between the Rieske center and the
      catalytic mononuclear iron center. Using Acinetobacter baumannii as the model, we
      then demonstrate that cntAB is essential in carnitine degradation to TMA.
      Heterologous overexpression of cntAB enables Escherichia coli to produce TMA,
      confirming that these genes are sufficient in TMA formation. Site-directed
      mutagenesis experiments have confirmed that this unusual "bridging glutamate"
      residue in CntA is essential in catalysis and neither mutant (E205D, E205A) is
      able to produce TMA. Taken together, the data in our study reveal the molecular
      and biochemical mechanisms underpinning carnitine metabolism to TMA in human
      microbiota and assign the role of this novel group of Rieske-type proteins in
      microbial carnitine metabolism.

PMID- 24591618
TI  - Identification of ocular dominance domains in New World owl monkeys by immediate
      early gene expression.
AB  - Ocular dominance columns (ODCs) have been well studied in the striate cortex (V1)
      of macaques, as well defined arrays of columnar structure that receive inputs
      from one eye or the other, whereas ODC expression seems more obscure in some New
      World primate species. ODCs have been identified by means of eye injections of
      transneuronal transporters and examination of cytochrome oxidase (CO) activity
      patterns after monocular enucleation. More recently, live-imaging techniques have
      been used to reveal ODCs. Here, we used the expression of immediate-early genes
      (IEGs), protooncogene, c-Fos, and zinc finger protein, Zif268, after monocular
      inactivation (MI) to identify ODCs in V1 of New World owl monkeys. Because IEG
      expression is more sensitive to activity changes than CO expression, it is
      capable of revealing activity maps in all layers throughout V1 and demonstrating
      brief activity changes within a couple of hours. Using IEGs, we not only revealed
      apparent ODCs in owl monkeys but also discovered a number of unique features of
      their ODCs. Distinct from those in macaques, these ODCs sometimes bridged to
      other columns in layer 4 (Brodmann layer 4C). CO blobs straddled ODC borders in
      the central visual field, whereas they centered ODC patches in the peripheral
      visual field. In one case, the ODC pattern continued into V2. Finally, an
      elevation of IEG expression in layer 4 (4C) was observed along ODC borders after
      only brief MI. Our data provide insights into the structure and variability of
      ODCs in primates and revive debate over the functions and development of ODCs.

PMID- 24591619
TI  - Requirement of MEF2A, C, and D for skeletal muscle regeneration.
AB  - Regeneration of adult skeletal muscle following injury occurs through the
      activation of satellite cells, an injury-sensitive muscle stem cell population
      that proliferates, differentiates, and fuses with injured myofibers. Members of
      the myocyte enhancer factor 2 (MEF2) family of transcription factors play
      essential roles in muscle differentiation during embryogenesis, but their
      potential contributions to adult muscle regeneration have not been systematically
      explored. To investigate the potential involvement of MEF2 factors in muscle
      regeneration, we conditionally deleted the Mef2a, c, and d genes, singly and in
      combination, within satellite cells in mice, using tamoxifen-inducible Cre
      recombinase under control of the satellite cell-specific Pax7 promoter. We show
      that deletion of individual Mef2 genes has no effect on muscle regeneration in
      response to cardiotoxin injury. However, combined deletion of the Mef2a, c, and d
      genes results in a blockade to regeneration. Satellite cell-derived myoblasts
      lacking MEF2A, C, and D proliferate normally in culture, but cannot
      differentiate. The absence of MEF2A, C, and D in satellite cells is associated
      with aberrant expression of a broad collection of known and unique protein-coding
      and long noncoding RNA genes. These findings reveal essential and redundant roles
      of MEF2A, C, and D in satellite cell differentiation and identify a MEF2
      dependent transcriptome associated with skeletal muscle regeneration. 

PMID- 24591620
TI  - Structural basis for gating mechanisms of a eukaryotic P-glycoprotein homolog.
AB  - P-glycoprotein is an ATP-binding cassette multidrug transporter that actively
      transports chemically diverse substrates across the lipid bilayer. The precise
      molecular mechanism underlying transport is not fully understood. Here, we
      present crystal structures of a eukaryotic P-glycoprotein homolog, CmABCB1 from
      Cyanidioschyzon merolae, in two forms: unbound at 2.6-A resolution and bound to a
      unique allosteric inhibitor at 2.4-A resolution. The inhibitor clamps the
      transmembrane helices from the outside, fixing the CmABCB1 structure in an inward
      open conformation similar to the unbound structure, confirming that an outward
      opening motion is required for ATP hydrolysis cycle. These structures, along with
      site-directed mutagenesis and transporter activity measurements, reveal the
      detailed architecture of the transporter, including a gate that opens to
      extracellular side and two gates that open to intramembranous region and the
      cytosolic side. We propose that the motion of the nucleotide-binding domain
      drives those gating apparatuses via two short intracellular helices, IH1 and IH2,
      and two transmembrane helices, TM2 and TM5. 

PMID- 24591621
TI  - Parkinson disease-associated mutation R1441H in LRRK2 prolongs the "active state"
      of its GTPase domain.
AB  - Mutation in leucine-rich-repeat kinase 2 (LRRK2) is a common cause of Parkinson
      disease (PD). A disease-causing point mutation R1441H/G/C in the GTPase domain of
      LRRK2 leads to overactivation of its kinase domain. However, the mechanism by
      which this mutation alters the normal function of its GTPase domain [Ras of
      complex proteins (Roc)] remains unclear. Here, we report the effects of R1441H
      mutation (RocR1441H) on the structure and activity of Roc. We show that Roc forms
      a stable monomeric conformation in solution that is catalytically active, thus
      demonstrating that LRRK2 is a bona fide self-contained GTPase. We further show
      that the R1441H mutation causes a twofold reduction in GTPase activity without
      affecting the structure, thermal stability, and GDP-binding affinity of Roc.
      However, the mutation causes a twofold increase in GTP-binding affinity of Roc,
      thus suggesting that the PD-causing mutation R1441H traps Roc in a more
      persistently activated state by increasing its affinity for GTP and, at the same
      time, compromising its GTP hydrolysis. 

PMID- 24591622
TI  - Hippocampal molecular mechanisms involved in the enhancement of fear extinction
      caused by exposure to novelty.
AB  - Exposure to a novel environment enhances the extinction of contextual fear. This
      has been explained by tagging of the hippocampal synapses used in extinction,
      followed by capture of proteins from the synapses that process novelty. The
      effect is blocked by the inhibition of hippocampal protein synthesis following
      the novelty or the extinction. Here, we show that it can also be blocked by the
      postextinction or postnovelty intrahippocampal infusion of the NMDA receptor
      antagonist 2-amino-5-phosphono pentanoic acid; the inhibitor of
      calcium/calmodulin-dependent protein kinase II (CaMKII), autocamtide-2-related
      inhibitory peptide; or the blocker of L-voltage-dependent calcium channels (L
      VDCCs), nifedipine. Inhibition of proteasomal protein degradation by beta
      lactacystin has no effect of its own on extinction or on the influence of novelty
      thereon but blocks the inhibitory effects of all the other substances except that
      of rapamycin on extinction, suggesting that their action depends on concomitant
      synaptic protein turnover. Thus, the tagging-and-capture mechanism through which
      novelty enhances fear extinction involves more molecular processes than hitherto
      thought: NMDA receptors, L-VDCCs, CaMKII, and synaptic protein turnover. 

PMID- 24591623
TI  - Increasing homogeneity in global food supplies and the implications for food
      security.
AB  - The narrowing of diversity in crop species contributing to the world's food
      supplies has been considered a potential threat to food security. However,
      changes in this diversity have not been quantified globally. We assess trends
      over the past 50 y in the richness, abundance, and composition of crop species in
      national food supplies worldwide. Over this period, national per capita food
      supplies expanded in total quantities of food calories, protein, fat, and weight,
      with increased proportions of those quantities sourcing from energy-dense foods.
      At the same time the number of measured crop commodities contributing to national
      food supplies increased, the relative contribution of these commodities within
      these supplies became more even, and the dominance of the most significant
      commodities decreased. As a consequence, national food supplies worldwide became
      more similar in composition, correlated particularly with an increased supply of
      a number of globally important cereal and oil crops, and a decline of other
      cereal, oil, and starchy root species. The increase in homogeneity worldwide
      portends the establishment of a global standard food supply, which is relatively
      species-rich in regard to measured crops at the national level, but species-poor
      globally. These changes in food supplies heighten interdependence among countries
      in regard to availability and access to these food sources and the genetic
      resources supporting their production, and give further urgency to nutrition
      development priorities aimed at bolstering food security. 

PMID- 24591624
TI  - Whole-genome sequencing of cultivated and wild peppers provides insights into
      Capsicum domestication and specialization.
AB  - As an economic crop, pepper satisfies people's spicy taste and has medicinal uses
      worldwide. To gain a better understanding of Capsicum evolution, domestication,
      and specialization, we present here the genome sequence of the cultivated pepper
      Zunla-1 (C. annuum L.) and its wild progenitor Chiltepin (C. annuum var.
      glabriusculum). We estimate that the pepper genome expanded ~0.3 Mya (with
      respect to the genome of other Solanaceae) by a rapid amplification of
      retrotransposons elements, resulting in a genome comprised of ~81% repetitive
      sequences. Approximately 79% of 3.48-Gb scaffolds containing 34,476 protein
      coding genes were anchored to chromosomes by a high-density genetic map.
      Comparison of cultivated and wild pepper genomes with 20 resequencing accessions
      revealed molecular footprints of artificial selection, providing us with a list
      of candidate domestication genes. We also found that dosage compensation effect
      of tandem duplication genes probably contributed to the pungent diversification
      in pepper. The Capsicum reference genome provides crucial information for the
      study of not only the evolution of the pepper genome but also, the Solanaceae
      family, and it will facilitate the establishment of more effective pepper
      breeding programs. 

PMID- 24591626
TI  - Principles of scientific research team formation and evolution.
AB  - Research teams are the fundamental social unit of science, and yet there is
      currently no model that describes their basic property: size. In most fields,
      teams have grown significantly in recent decades. We show that this is partly due
      to the change in the character of team size distribution. We explain these
      changes with a comprehensive yet straightforward model of how teams of different
      sizes emerge and grow. This model accurately reproduces the evolution of
      empirical team size distribution over the period of 50 y. The modeling reveals
      that there are two modes of knowledge production. The first and more fundamental
      mode employs relatively small, "core" teams. Core teams form by a Poisson process
      and produce a Poisson distribution of team sizes in which larger teams are
      exceedingly rare. The second mode employs "extended" teams, which started as core
      teams, but subsequently accumulated new members proportional to the past
      productivity of their members. Given time, this mode gives rise to a power-law
      tail of large teams (10-1,000 members), which features in many fields today.
      Based on this model, we construct an analytical functional form that allows the
      contribution of different modes of authorship to be determined directly from the
      data and is applicable to any field. The model also offers a solid foundation for
      studying other social aspects of science, such as productivity and collaboration.

PMID- 24591625
TI  - C1q as a unique player in angiogenesis with therapeutic implication in wound
      healing.
AB  - We have previously shown that C1q is expressed on endothelial cells (ECs) of
      newly formed decidual tissue. Here we demonstrate that C1q is deposited in wound
      healing skin in the absence of C4 and C3 and that C1q mRNA is locally expressed
      as revealed by real-time PCR and in situ hybridization. C1q was found to induce
      permeability of the EC monolayer, to stimulate EC proliferation and migration,
      and to promote tube formation and sprouting of new vessels in a rat aortic ring
      assay. Using a murine model of wound healing we observed that vessel formation
      was defective in C1qa(-/-) mice and was restored to normal after local
      application of C1q. The mean vessel density of wound-healing tissue and the
      healed wound area were significantly increased in C1q-treated rats. On the basis
      of these results we suggest that C1q may represent a valuable therapeutic agent
      that can be used to treat chronic ulcers or other pathological conditions in
      which angiogenesis is impaired, such as myocardial ischemia. 

PMID- 24591627
TI  - Contextual effect of positive intergroup contact on outgroup prejudice.
AB  - We assessed evidence for a contextual effect of positive intergroup contact,
      whereby the effect of intergroup contact between social contexts (the between
      level effect) on outgroup prejudice is greater than the effect of individual
      level contact within contexts (the within-level effect). Across seven large-scale
      surveys (five cross-sectional and two longitudinal), using multilevel analyses,
      we found a reliable contextual effect. This effect was found in multiple
      countries, operationalizing context at multiple levels (regions, districts, and
      neighborhoods), and with and without controlling for a range of demographic and
      context variables. In four studies (three cross-sectional and one longitudinal)
      we showed that the association between context-level contact and prejudice was
      largely mediated by more tolerant norms. In social contexts where positive
      contact with outgroups was more commonplace, norms supported such positive
      interactions between members of different groups. Thus, positive contact reduces
      prejudice on a macrolevel, whereby people are influenced by the behavior of
      others in their social context, not merely on a microscale, via individuals'
      direct experience of positive contact with outgroup members. These findings
      reinforce the view that contact has a significant role to play in prejudice
      reduction, and has great policy potential as a means to improve intergroup
      relations, because it can simultaneously impact large numbers of people. 

PMID- 24591628
TI  - Activating mutations in STIM1 and ORAI1 cause overlapping syndromes of tubular
      myopathy and congenital miosis.
AB  - Signaling through the store-operated Ca(2+) release-activated Ca(2+) (CRAC)
      channel regulates critical cellular functions, including gene expression, cell
      growth and differentiation, and Ca(2+) homeostasis. Loss-of-function mutations in
      the CRAC channel pore-forming protein ORAI1 or the Ca(2+) sensing protein stromal
      interaction molecule 1 (STIM1) result in severe immune dysfunction and
      nonprogressive myopathy. Here, we identify gain-of-function mutations in the
      cytoplasmic domain of STIM1 (p.R304W) associated with thrombocytopenia, bleeding
      diathesis, miosis, and tubular myopathy in patients with Stormorken syndrome, and
      in ORAI1 (p.P245L), associated with a Stormorken-like syndrome of congenital
      miosis and tubular aggregate myopathy but without hematological abnormalities.
      Heterologous expression of STIM1 p.R304W results in constitutive activation of
      the CRAC channel in vitro, and spontaneous bleeding accompanied by reduced
      numbers of thrombocytes in zebrafish embryos, recapitulating key aspects of
      Stormorken syndrome. p.P245L in ORAI1 does not make a constitutively active CRAC
      channel, but suppresses the slow Ca(2+)-dependent inactivation of the CRAC
      channel, thus also functioning as a gain-of-function mutation. These data expand
      our understanding of the phenotypic spectrum of dysregulated CRAC channel
      signaling, advance our knowledge of the molecular function of the CRAC channel,
      and suggest new therapies aiming at attenuating store-operated Ca(2+) entry in
      the treatment of patients with Stormorken syndrome and related pathologic
      conditions. 

PMID- 24591629
TI  - Molecular mechanism and structure of the Saccharomyces cerevisiae iron regulator
      Aft2.
AB  - The paralogous iron-responsive transcription factors Aft1 and Aft2 (activators of
      ferrous transport) regulate iron homeostasis in Saccharomyces cerevisiae by
      activating expression of iron-uptake and -transport genes when intracellular iron
      is low. We present the previously unidentified crystal structure of Aft2 bound to
      DNA that reveals the mechanism of DNA recognition via specific interactions of
      the iron-responsive element with a Zn(2+)-containing WRKY-GCM1 domain in Aft2. We
      also show that two Aft2 monomers bind a [2Fe-2S] cluster (or Fe(2+)) through a
      Cys-Asp-Cys motif, leading to dimerization of Aft2 and decreased DNA-binding
      affinity. Furthermore, we demonstrate that the [2Fe-2S]-bridged heterodimer
      formed between glutaredoxin-3 and the BolA-like protein Fe repressor of
      activation-2 transfers a [2Fe-2S] cluster to Aft2 that facilitates Aft2
      dimerization. Previous in vivo findings strongly support the [2Fe-2S] cluster
      induced dimerization model; however, given the available evidence, Fe(2+)-induced
      Aft2 dimerization cannot be completely ruled out as an alternative Aft2
      inhibition mechanism. Taken together, these data provide insight into the
      molecular mechanism for iron-dependent transcriptional regulation of Aft2 and
      highlight the key role of Fe-S clusters as cellular iron signals. 

PMID- 24591630
TI  - Differential regulation of S-region hypermutation and class-switch recombination
      by noncanonical functions of uracil DNA glycosylase.
AB  - Activation-induced cytidine deaminase (AID) is essential to class-switch
      recombination (CSR) and somatic hypermutation (SHM) in both V region SHM and S
      region SHM (s-SHM). Uracil DNA glycosylase (UNG), a member of the base excision
      repair (BER) complex, is required for CSR. Strikingly, however, UNG deficiency
      causes augmentation of SHM, suggesting involvement of distinct functions of UNG
      in SHM and CSR. Here, we show that noncanonical scaffold functions of UNG
      regulate s-SHM negatively and CSR positively. The s-SHM suppressive function of
      UNG is attributed to the recruitment of faithful BER components at the cleaved
      DNA locus, with competition against error-prone polymerases. By contrast, the CSR
      promoting function of UNG enhances AID-dependent S-S synapse formation by
      recruiting p53-binding protein 1 and DNA-dependent protein kinase, catalytic
      subunit. Several loss-of-catalysis mutants of UNG discriminated CSR-promoting
      activity from s-SHM suppressive activity. Taken together, the noncanonical
      function of UNG regulates the steps after AID-induced DNA cleavage: error-prone
      repair suppression in s-SHM and end-joining promotion in CSR. 

PMID- 24591632
TI  - Endogenous localizome identifies 43 mitotic kinesins in a plant cell.
AB  - Kinesins are microtubule (MT)-based motor proteins that have been identified in
      every eukaryotic species. Intriguingly, land plants have more than 60 kinesins in
      their genomes, many more than that in yeasts or animals. However, many of these
      have not yet been characterized, and their cellular functions are unknown. Here,
      by using endogenous tagging, we comprehensively determined the localization of 72
      kinesins during mitosis in the moss Physcomitrella patens. We found that 43
      kinesins are localized to mitotic structures such as kinetochores, spindle MTs,
      or phragmoplasts, which are MT-based structures formed during cytokinesis.
      Surprisingly, only one of them showed an identical localization pattern to the
      animal homolog, and many were enriched at unexpected sites. RNA interference and
      live-cell microscopy revealed postanaphase roles for kinesin-5 in
      spindle/phragmoplast organization, chromosome segregation, and cytokinesis, which
      have not been observed in animals. Our study thus provides a list of MT-based
      motor proteins associated with the cell division machinery in plants.
      Furthermore, our data challenge the current generalization of determining mitotic
      kinesin function based solely on studies using yeast and animal cells. 

PMID- 24591633
TI  - High herbivore density associated with vegetation diversity in interglacial
      ecosystems.
AB  - The impact of large herbivores on ecosystems before modern human activities is an
      open question in ecology and conservation. For Europe, the controversial wood
      pasture hypothesis posits that grazing by wild large herbivores supported a
      dynamic mosaic of vegetation structures at the landscape scale under temperate
      conditions before agriculture. The contrasting position suggests that European
      temperate vegetation was primarily closed forest with relatively small open
      areas, at most impacted locally by large herbivores. Given the role of modern
      humans in the world-wide decimations of megafauna during the late Quaternary, to
      resolve this debate it is necessary to understand herbivore-vegetation
      interactions before these losses. Here, a synthetic analysis of beetle fossils
      from Great Britain shows that beetles associated with herbivore dung were better
      represented during the Last Interglacial (132,000-110,000 y B.P., before modern
      human arrival) than in the early Holocene (10,000-5,000 y B.P.). Furthermore,
      beetle assemblages indicate closed and partially closed forest in the early
      Holocene but a greater mixture of semiopen vegetation and forest in the Last
      Interglacial. Hence, abundant and diverse large herbivores appear to have been
      associated with high structural diversity of vegetation before the megafauna
      extinctions at the end of the Pleistocene. After these losses and in the presence
      of modern humans, large herbivores generally were less abundant, and closed
      woodland was more prevalent in the early Holocene. Our findings point to the
      importance of the formerly rich fauna of large herbivores in sustaining
      structurally diverse vegetation in the temperate forest biome and provide support
      for recent moves toward rewilding-based conservation management. 

PMID- 24591631
TI  - microRNAs are biomarkers of oncogenic human papillomavirus infections.
AB  - Cellular and viral microRNAs (miRNAs) are the transcriptional products of RNA
      polymerase II and are regulated by transcriptional factors for their differential
      expression. The altered expression of miRNAs in many cancer types has been
      explored as a marker for possible diagnosis and therapy. We report in this study
      that oncogenic human papillomaviruses (HPVs) induce aberrant expression of many
      cellular miRNAs and that HPV18 infection produces no detectable viral miRNA.
      Thirteen abundant host miRNAs were specifically regulated by HPV16 and HPV18 in
      organotypic raft cultures of foreskin and vaginal keratinocytes as determined by
      miRNA array in combination with small RNA sequencing. The increase of miR-16, miR
      25, miR-92a, and miR-378 and the decrease of miR-22, miR-27a, miR-29a, and miR
      100 could be attributed to viral oncoprotein E6, E7, or both, all of which are
      known to target many cellular transcription factors. The examination of 158
      cervical specimens, including 38 normal, 52 cervical intraepithelial neoplasia
      (CIN), and 68 cervical cancer (CC) tissues, for the expression of these eight
      miRNAs showed a remarkable increase of miR-25, miR-92a, and miR-378 with lesion
      progression but no obvious change of miR-22, miR-29a, and miR-100 among the HPV
      infected tissues. Further analyses indicate that an expression ratio >=1.5 of miR
      25/92a group over miR-22/29a group could serve as a cutoff value to distinguish
      normal cervix from CIN and from CIN to CC. 

PMID- 24591634
TI  - BMP signaling is required for the generation of primordial germ cells in an
      insect.
AB  - Two modes of germ cell formation are known in animals. Specification through
      maternally inherited germ plasm occurs in many well-characterized model
      organisms, but most animals lack germ plasm by morphological and functional
      criteria. The only known alternative mechanism is induction, experimentally
      described only in mice, which specify germ cells through bone morphogenetic
      protein (BMP) signal-mediated induction of a subpopulation of mesodermal cells.
      Until this report, no experimental evidence of an inductive germ cell signal for
      specification has been available outside of vertebrates. Here we provide
      functional genetic experimental evidence consistent with a role for BMP signaling
      in germ cell formation in a basally branching insect. We show that primordial
      germ cells of the cricket Gryllus bimaculatus transduce BMP signals and require
      BMP pathway activity for their formation. Moreover, increased BMP activity leads
      to ectopic and supernumerary germ cells. Given the commonality of BMP signaling
      in mouse and cricket germ cell induction, we suggest that BMP-based germ cell
      formation may be a shared ancestral mechanism in animals. 

PMID- 24591635
TI  - Mapping posttranscriptional regulation of the human glycome uncovers microRNA
      defining the glycocode.
AB  - Cell surface glycans form a critical interface with the biological milieu,
      informing diverse processes from the inflammatory cascade to cellular migration.
      Assembly of discrete carbohydrate structures requires the coordinated activity of
      a repertoire of proteins, including glycosyltransferases and glycosidases. Little
      is known about the regulatory networks controlling this complex biosynthetic
      process. Recent work points to a role for microRNA (miRNA) in the regulation of
      specific glycan biosynthetic enzymes. Herein we take a unique systems-based
      approach to identify connections between miRNA and the glycome. By using our
      glycomic analysis platform, lectin microarrays, we identify glycosylation
      signatures in the NCI-60 cell panel that point to the glycome as a direct output
      of genomic information flow. Integrating our glycomic dataset with miRNA data, we
      map miRNA regulators onto genes in glycan biosynthetic pathways (glycogenes) that
      generate the observed glycan structures. We validate three of these predicted
      miRNA/glycogene regulatory networks: high mannose, fucose, and terminal beta
      GalNAc, identifying miRNA regulation that would not have been observed by
      traditional bioinformatic methods. Overall, our work reveals critical nodes in
      the global glycosylation network accessible to miRNA regulation, providing a
      bridge between miRNA-mediated control of cell phenotype and the glycome. 

PMID- 24591636
TI  - Marginal zone CD169+ macrophages coordinate apoptotic cell-driven cellular
      recruitment and tolerance.
AB  - Tolerance to apoptotic cells is essential to prevent inflammatory pathology.
      Though innate responses are critical for immune suppression, our understanding of
      early innate immunity driven by apoptosis is lacking. Herein we report apoptotic
      cells induce expression of the chemokine CCL22 in splenic metallophillic
      macrophages, which is critical for tolerance. Systemic challenge with apoptotic
      cells induced rapid production of CCL22 in CD169(+) (metallophillic) macrophages,
      resulting in accumulation and activation of FoxP3(+) Tregs and CD11c(+) dendritic
      cells, an effect that could be inhibited by antagonizing CCL22-driven chemotaxis.
      This mechanism was essential for suppression after apoptotic cell challenge,
      because neutralizing CCL22 or its receptor, reducing Treg numbers, or blocking
      effector mechanisms abrogated splenic TGF-beta and IL-10 induction; this promoted
      a shift to proinflammatory cytokines associated with a failure to suppress T
      cells. Similarly, CCR4 inhibition blocked long-term, apoptotic cell-induced
      tolerance to allografts. Finally, CCR4 inhibition resulted in a systemic
      breakdown of tolerance to self after apoptotic cell injection with rapid
      increases in anti-dsDNA IgG and immune complex deposition. Thus, the data
      demonstrate CCL22-dependent chemotaxis is a key early innate response required
      for apoptotic cell-induced suppression, implicating a previously unknown
      mechanism of macrophage-dependent coordination of early events leading to stable
      tolerance. 

PMID- 24591637
TI  - Ablation of the oncogenic transcription factor ERG by deubiquitinase inhibition
      in prostate cancer.
AB  - The transcription factor E-twenty-six related gene (ERG), which is overexpressed
      through gene fusion with the androgen-responsive gene transmembrane protease,
      serine 2 (TMPRSS2) in ~40% of prostate tumors, is a key driver of prostate
      carcinogenesis. Ablation of ERG would disrupt a key oncogenic transcriptional
      circuit and could be a promising therapeutic strategy for prostate cancer
      treatment. Here, we show that ubiquitin-specific peptidase 9, X-linked (USP9X), a
      deubiquitinase enzyme, binds ERG in VCaP prostate cancer cells expressing TMPRSS2
      ERG and deubiquitinates ERG in vitro. USP9X knockdown resulted in increased
      levels of ubiquitinated ERG and was coupled with depletion of ERG. Treatment with
      the USP9X inhibitor WP1130 resulted in ERG degradation both in vivo and in vitro,
      impaired the expression of genes enriched in ERG and prostate cancer relevant
      gene signatures in microarray analyses, and inhibited growth of ERG-positive
      tumors in three mouse xenograft models. Thus, we identified USP9X as a potential
      therapeutic target in prostate cancer cells and established WP1130 as a lead
      compound for the development of ERG-depleting drugs. 

PMID- 24591638
TI  - Circulating hematopoietic stem and progenitor cells are myeloid-biased in cancer
      patients.
AB  - Cancer is associated with a profound perturbation in myelopoiesis that results in
      the accumulation of myeloid-derived suppressor cells (MDSCs) to promote disease
      progression. Recent studies in mice suggest that tumor-derived factors could
      regulate the differentiation of hematopoietic stem and progenitor cells (HSPCs)
      in the bone marrow and subsequently contribute to dysregulation of hematopoiesis.
      However, the nature and role of HPSCs in patients with cancer remain unknown.
      Here we show, in detailed studies of the peripheral blood from 133 untreated
      patients with seven different types of tumors, that the composition of
      circulating HSPCs was significantly altered in patients with solid tumors. The
      frequencies of circulating granulocyte-monocyte progenitors (GMPs) were increased
      four to seven fold in all types of tumors examined, and the circulating
      hematopoietic precursors exhibited myeloid bias with a skew toward granulocytic
      differentiation in patients with solid tumors. These myeloid precursors are
      selectively enriched in tumor tissues, and the high levels of circulating GMPs
      were positively correlated with disease progression. By using cord blood-derived
      CD34(+) cells, we developed an in vitro short-term culture model to effectively
      induce the rapid generation of MDSCs. We found that, among the factors produced
      by various tumors, GM-CSF, granulocyte colony-stimulating factor, and IL-6 could
      not only promote the myeloid-biased differentiation, but also induce the
      differentiation of myeloid precursors into functional MDSCs. These findings
      suggest that the altered circulating HSPCs may serve as an important link between
      dysregulated bone marrow hematopoiesis and accumulated MDSCs in patients with
      cancer. 

PMID- 24591639
TI  - Fine mapping of genome activation in bovine embryos by RNA sequencing.
AB  - During maternal-to-embryonic transition control of embryonic development
      gradually switches from maternal RNAs and proteins stored in the oocyte to gene
      products generated after embryonic genome activation (EGA). Detailed insight into
      the onset of embryonic transcription is obscured by the presence of maternal
      transcripts. Using the bovine model system, we established by RNA sequencing a
      comprehensive catalogue of transcripts in germinal vesicle and metaphase II
      oocytes, and in embryos at the four-cell, eight-cell, 16-cell, and blastocyst
      stages. These were produced by in vitro fertilization of Bos taurus taurus
      oocytes with sperm from a Bos taurus indicus bull to facilitate parent-specific
      transcriptome analysis. Transcripts from 12.4 to 13.7 * 10(3) different genes
      were detected in the various developmental stages. EGA was analyzed by (i)
      detection of embryonic transcripts, which are not present in oocytes; (ii)
      detection of transcripts from the paternal allele; and (iii) detection of primary
      transcripts with intronic sequences. These strategies revealed (i) 220, (ii) 937,
      and (iii) 6,848 genes to be activated from the four-cell to the blastocyst stage.
      The largest proportion of gene activation [i.e., (i) 59%, (ii) 42%, and (iii)
      58%] was found in eight-cell embryos, indicating major EGA at this stage. Gene
      ontology analysis of genes activated at the four-cell stage identified categories
      related to RNA processing, translation, and transport, consistent with
      preparation for major EGA. Our study provides the largest transcriptome data set
      of bovine oocyte maturation and early embryonic development and detailed insight
      into the timing of embryonic activation of specific genes. 

PMID- 24591640
TI  - Tumor suppressor role of phospholipase C epsilon in Ras-triggered cancers.
AB  - Phospholipase Cepsilon (PLCepsilon) has been characterized as a direct effector
      of Ras in vitro and in cellular systems; however, the role of PLCepsilon in
      tumorigenesis and its link to Ras in this context remain unclear. To assess the
      role of PLCepsilon in Ras-driven cancers, we generated two new mouse strains: one
      carrying a targeted deletion of Plce (Plce(-/-)) and the other carrying mutant
      alleles of Plce unable to bind to Ras (Plce(RAm/RAm)). The Plce(-/-) and, to a
      lesser degree, Plce(RAm/RAm) transgenic mice exhibited increased susceptibility
      to tumor formation in the two-stage skin carcinogenesis protocol, revealing a
      tumor suppressor function for this PLC. This result also suggests that in this
      context Ras binding in part regulates functions of PLCepsilon. Although
      significant differences were not seen in the LSL-Kras(G12D) nonsmall cell lung
      carcinoma model, down-regulation of PLCepsilon was found in animal tumors and in
      cellular systems following expression of the oncogenic Ras. An inhibitory impact
      of PLCepsilon on cell growth requires intact lipase activity and is likely
      mediated by protein kinase C enzymes. Further cellular studies suggest
      involvement of histone deacetylase in the mechanism of PLCepsilon down
      regulation. Taken together, our results show a previously unidentified tumor
      suppressor role for this PLC in animal models and, together with observations of
      marked down-regulation in colorectal, lung, and skin tumors, suggest its use as a
      biological marker in cancer. 

PMID- 24591641
TI  - Binding of Pro-Gly-Pro at the active site of leukotriene A4
      hydrolase/aminopeptidase and development of an epoxide hydrolase selective
      inhibitor.
AB  - Leukotriene (LT) A4 hydrolase/aminopeptidase (LTA4H) is a bifunctional zinc
      metalloenzyme that catalyzes the committed step in the formation of the
      proinflammatory mediator LTB4. Recently, the chemotactic tripeptide Pro-Gly-Pro
      was identified as an endogenous aminopeptidase substrate for LTA4 hydrolase.
      Here, we determined the crystal structure of LTA4 hydrolase in complex with a Pro
      Gly-Pro analog at 1.72 A. From the structure, which includes the catalytic water,
      and mass spectrometric analysis of enzymatic hydrolysis products of Pro-Gly-Pro,
      it could be inferred that LTA4 hydrolase cleaves at the N terminus of the
      palindromic tripeptide. Furthermore, we designed a small molecule, 4-(4
      benzylphenyl)thiazol-2-amine, denoted ARM1, that inhibits LTB4 synthesis in human
      neutrophils (IC50 of ~0.5 MUM) and conversion of LTA4 into LTB4 by purified LTA4H
      with a Ki of 2.3 MUM. In contrast, 50- to 100-fold higher concentrations of ARM1
      did not significantly affect hydrolysis of Pro-Gly-Pro. A 1.62-A crystal
      structure of LTA4 hydrolase in a dual complex with ARM1 and the Pro-Gly-Pro
      analog revealed that ARM1 binds in the hydrophobic pocket that accommodates the
      omega-end of LTA4, distant from the aminopeptidase active site, thus providing a
      molecular basis for its inhibitory profile. Hence, ARM1 selectively blocks
      conversion of LTA4 into LTB4, although sparing the enzyme's anti-inflammatory
      aminopeptidase activity (i.e., degradation and inactivation of Pro-Gly-Pro). ARM1
      represents a new class of LTA4 hydrolase inhibitor that holds promise for
      improved anti-inflammatory properties. 

PMID- 24591642
TI  - Understanding the antagonism of retinoblastoma protein dephosphorylation by PNUTS
      provides insights into the PP1 regulatory code.
AB  - The serine/threonine protein phosphatase 1 (PP1) dephosphorylates hundreds of key
      biological targets by associating with nearly 200 regulatory proteins to form
      highly specific holoenzymes. However, how these proteins direct PP1 specificity
      and the ability to predict how these PP1 interacting proteins bind PP1 from
      sequence alone is still missing. PP1 nuclear targeting subunit (PNUTS) is a PP1
      targeting protein that, with PP1, plays a central role in the nucleus, where it
      regulates chromatin decondensation, RNA processing, and the phosphorylation state
      of fundamental cell cycle proteins, including the retinoblastoma protein (Rb),
      p53, and MDM2. The molecular function of PNUTS in these processes is completely
      unknown. Here, we show that PNUTS, which is intrinsically disordered in its free
      form, interacts strongly with PP1 in a highly extended manner. Unexpectedly,
      PNUTS blocks one of PP1's substrate binding grooves while leaving the active site
      accessible. This interaction site, which we have named the arginine site, allowed
      us to define unique PP1 binding motifs, which advances our ability to predict how
      more than a quarter of the known PP1 regulators bind PP1. Additionally, the
      structure shows how PNUTS inhibits the PP1-mediated dephosphorylation of critical
      substrates, especially Rb, by blocking their binding sites on PP1, insights that
      are providing strategies for selectively enhancing Rb activity. 

PMID- 24591643
TI  - Redesign of extensive protein-DNA interfaces of meganucleases using iterative
      cycles of in vitro compartmentalization.
AB  - LAGLIDADG homing endonucleases (meganucleases) are sequence-specific DNA cleavage
      enzymes used for genome engineering. Recently, meganucleases fused to
      transcription activator-like effectors have been demonstrated to efficiently
      introduce targeted genome modifications. However, retargeting meganucleases to
      genomic sequences of interest remains challenging because it usually requires
      extensive alteration of a large number of amino acid residues that are situated
      in and near the DNA interface. Here we describe an effective strategy to
      extensively redesign such an extensive biomolecular interface. Well-characterized
      meganucleases are computationally screened to identify the best candidate enzyme
      to target a genomic region; that protein is then redesigned using iterative
      rounds of in vitro selections within compartmentalized aqueous droplets, which
      enable screening of extremely large numbers of protein variants at each step. The
      utility of this approach is illustrated by engineering three different
      meganucleases to cleave three human genomic sites (found in two exons and one
      flanking intron in two clinically relevant genes) and a fourth endonuclease that
      discriminates between single-nucleotide polymorphism variants of one of those
      targets. Fusion with transcription activator-like effector DNA binding domains
      significantly enhances targeted modification induced by meganucleases engineered
      in this study. Simultaneous expression of two such fusion endonucleases results
      in efficient excision of a defined genomic region. 

PMID- 24591644
TI  - Dendritic cell fate is determined by BCL11A.
AB  - The plasmacytoid dendritic cell (pDC) is vital to the coordinated action of
      innate and adaptive immunity. pDC development has not been unequivocally traced,
      nor has its transcriptional regulatory network been fully clarified. Here we
      confirm an essential requirement for the BCL11A transcription factor in fetal pDC
      development, and demonstrate this lineage-specific requirement in the adult
      organism. Furthermore, we identify BCL11A gene targets and provide a molecular
      mechanism for its action in pDC commitment. Embryonic germ-line deletion of
      Bcl11a revealed an absolute cellular, molecular, and functional absence of pDCs
      in fetal mice. In adults, deletion of Bcl11a in hematopoietic stem cells resulted
      in perturbed yet continued generation of progenitors, loss of downstream pDC and
      B-cell lineages, and persisting myeloid, conventional dendritic, and T-cell
      lineages. Challenge with virus resulted in a marked reduction of antiviral
      response in conditionally deleted adults. Genome-wide analyses of BCL11A DNA
      binding and expression revealed that BCL11A regulates transcription of E2-2 and
      other pDC differentiation modulators, including ID2 and MTG16. Our results
      identify BCL11A as an essential, lineage-specific factor that regulates pDC
      development, supporting a model wherein differentiation into pDCs represents a
      primed "default" pathway for common dendritic cell progenitors. 

PMID- 24591645
TI  - Individual IKs channels at the surface of mammalian cells contain two KCNE1
      accessory subunits.
AB  - KCNE1 (E1) beta-subunits assemble with KCNQ1 (Q1) voltage-gated K(+) channel
      alpha-subunits to form IKslow (IKs) channels in the heart and ear. The number of
      E1 subunits in IKs channels has been an issue of ongoing debate. Here, we use
      single-molecule spectroscopy to demonstrate that surface IKs channels with human
      subunits contain two E1 and four Q1 subunits. This stoichiometry does not vary.
      Thus, IKs channels in cells with elevated levels of E1 carry no more than two E1
      subunits. Cells with low levels of E1 produce IKs channels with two E1 subunits
      and Q1 channels with no E1 subunits--channels with one E1 do not appear to form
      or are restricted from surface expression. The plethora of models of cardiac
      function, transgenic animals, and drug screens based on variable E1 stoichiometry
      do not reflect physiology.

PMID- 24591646
TI  - Myosin lever arm directs collective motion on cellular actin network.
AB  - The molecular motor myosin teams up to drive muscle contraction, membrane
      traffic, and cell division in biological cells. Myosin function in cells emerges
      from the interaction of multiple motors tethered to a scaffold, with surrounding
      actin filaments organized into 3D networks. Despite the importance of myosin
      function, the influence of intermotor interactions on collective motion remains
      poorly understood. In this study, we used precisely engineered myosin assemblies
      to examine emergence in collective myosin movement. We report that tethering
      multiple myosin VI motors, but not myosin V motors, modifies their movement
      trajectories on keratocyte actin networks. Single myosin V and VI dimers display
      similar skewed trajectories, albeit in opposite directions, when traversing the
      keratocyte actin network. In contrast, tethering myosin VI motors, but not myosin
      V motors, progressively straightens the trajectories with increasing myosin
      number. Trajectory shape of multimotor scaffolds positively correlates with the
      stiffness of the myosin lever arm. Swapping the flexible myosin VI lever arm for
      the relatively rigid myosin V lever increases trajectory skewness, and vice
      versa. A simplified model of coupled motor movement demonstrates that the
      differences in flexural rigidity of the two myosin lever arms is sufficient to
      account for the differences in observed behavior of groups of myosin V and VI
      motors. In accordance with this model trajectory, shapes for scaffolds containing
      both myosin V and VI are dominated by the myosin with a stiffer lever arm. Our
      findings suggest that structural features unique to each myosin type may confer
      selective advantages in cellular functions. 

PMID- 24591647
TI  - Molecular interferometer to decode attosecond electron-nuclear dynamics.
AB  - Understanding the coupled electronic and nuclear dynamics in molecules by using
      pump-probe schemes requires not only the use of short enough laser pulses but
      also wavelengths and intensities that do not modify the intrinsic behavior of the
      system. In this respect, extreme UV pulses of few-femtosecond and attosecond
      durations have been recognized as the ideal tool because their short wavelengths
      ensure a negligible distortion of the molecular potential. In this work, we
      propose the use of two twin extreme UV pulses to create a molecular
      interferometer from direct and sequential two-photon ionization processes that
      leave the molecule in the same final state. We theoretically demonstrate that
      such a scheme allows for a complete identification of both electronic and nuclear
      phases in the wave packet generated by the pump pulse. We also show that although
      total ionization yields reveal entangled electronic and nuclear dynamics in the
      bound states, doubly differential yields (differential in both electronic and
      nuclear energies) exhibit in addition the dynamics of autoionization, i.e., of
      electron correlation in the ionization continuum. Visualization of such dynamics
      is possible by varying the time delay between the pump and the probe pulses. 

PMID- 24591648
TI  - Toxic encephalopathy due to colchicine--Gloriosa superba poisoning.
AB  - Gloriosa superba, a flowering plant widespread in South and Southeast Asia, is
      implicated in many cases of self-poisoning. Colchicine is concentrated in the
      seeds and tubers and this mediates its toxicity. We describe a 28-year-old woman
      who developed delayed encephalopathy after eating G superba tubers. MR scan of
      brain showed bilateral symmetrical T2 basal ganglia hyperintensities in the
      caudate and lentiform nuclei. The delay in onset of encephalopathy is
      attributable to a direct-effect colchicine, probably mediated through its effect
      on microtubular transport.

PMID- 24591649
TI  - A cluster of thin tubular structures mediates transformation of the endoplasmic
      reticulum to autophagic isolation membrane.
AB  - Recent findings have suggested that the autophagic isolation membrane (IM) might
      originate from a domain of the endoplasmic reticulum (ER) called the omegasome.
      However, the morphological relationships between ER, omegasome, and IM remain
      unclear. In the present study, we found that hybrid structures composed of a
      double FYVE domain-containing protein 1 (DFCP1)-positive omegasome and the IM
      accumulated in Atg3-deficient mouse embryonic fibroblasts (MEFs). Moreover,
      correlative light and electron microscopy and immunoelectron microscopy revealed
      that green fluorescent protein (GFP)-tagged DFCP1 was localized on tubular or
      vesicular elements adjacent to the IM rims. Through detailed morphological
      analyses, including optimization of a fixation method and electron tomography, we
      observed a cluster of thin tubular structures between the IM edges and ER, part
      of which were continuous with IM and/or ER. The formation of these thin tubular
      clusters was observed in several cell lines and MEFs deficient for Atg5, Atg7, or
      Atg16L1 but not in FIP200-deficient cells, suggesting that they were relevant to
      the earlier events in autophagosome formation. Taken together, our findings
      indicate that these tubular profiles represent a part of the omegasome that links
      the ER with the IM. 

PMID- 24591650
TI  - Ligand promiscuity of aryl hydrocarbon receptor agonists and antagonists revealed
      by site-directed mutagenesis.
AB  - The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor
      that can be activated by structurally diverse chemicals. To examine the
      mechanisms responsible for the promiscuity in AhR ligand binding, we determined
      the effects of mutations within the AhR ligand-binding domain (LBD) on the
      activity of diverse AhR ligands. Site-directed mutagenesis identified Ile319 of
      the mouse AhR and, to a lesser extent, Phe318 as residues involved in ligand
      selective modulation of AhR transformation using a panel of 12 AhR ligands. These
      ligands could be categorized into four distinct structurally related groups based
      on their ability to activate AhR mutants at position 319 in vitro. The mutation
      I319K was selectively activated by FICZ and not by other examined ligands in
      vitro and in cell culture. F318L and F318A mutations resulted in the conversion
      of AhR agonists beta-naphthoflavone and 3-methylcholanthrene, respectively, into
      partial agonists/antagonists. Hsp90 binding to the AhR was decreased with several
      mutations and was inversely correlated with AhR ligand-binding promiscuity.
      Together, these data define overlapping amino acid residues within the AhR LBD
      involved in the selectivity of ligand binding, the agonist or antagonist mode of
      ligand binding, and hsp90 binding and provide insights into the ligand diversity
      of AhR activators. 

PMID- 24591652
TI  - Tsc2 is a molecular checkpoint controlling osteoblast development and glucose
      homeostasis.
AB  - Insulin signaling in osteoblasts regulates global energy balance by stimulating
      the production of osteocalcin, a bone-derived protein that promotes insulin
      production and action. To identify the signaling pathways in osteoblasts that
      mediate insulin's effects on bone and energy metabolism, we examined the function
      of the tuberous sclerosis 2 (Tsc2) protein, a key target important in
      coordinating nutrient signaling. Here, we show that loss of Tsc2 in osteoblasts
      constitutively activates mTOR and destabilizes Irs1, causing osteoblasts to
      differentiate poorly and become resistant to insulin. Young Tsc2 mutant mice
      demonstrate hypoglycemia with increased levels of insulin and undercarboxylated
      osteocalcin. However, with age, Tsc2 mutants develop metabolic features similar
      to mice lacking the insulin receptor in the osteoblast, including peripheral
      adiposity, hyperglycemia, and decreased pancreatic beta cell mass. These
      metabolic abnormalities appear to result from chronic elevations in
      undercarboxylated osteocalcin that lead to downregulation of the osteocalcin
      receptor and desensitization of the beta cell to this hormone. Removal of a
      single mTOR allele from the Tsc2 mutant mice largely normalizes the bone and
      metabolic abnormalities. Together, these findings suggest that Tsc2 serves as a
      key checkpoint in the osteoblast that is required for proper insulin signaling
      and acts to ensure normal bone acquisition and energy homeostasis. 

PMID- 24591653
TI  - Homer1 alternative splicing is regulated by gonadotropin-releasing hormone and
      modulates gonadotropin gene expression.
AB  - Hypothalamic gonadotropin-releasing hormone (GnRH) plays a critical role in
      reproductive physiology by regulating follicle-stimulating hormone (FSH) and
      luteinizing hormone (LH) gene expression in the pituitary. Analysis of
      gonadotrope deep-sequencing data identified a global regulation of pre-mRNA
      splicing by GnRH. Homer1, a gene encoding a postsynaptic density scaffolding
      protein, was selected for further study. Homer1 expresses a short splice form,
      Homer1a, and more-abundant long transcripts Homer1b/c. GnRH induced a modest
      increase in Homer1b/c expression and a dramatic increase in the Homer1a splice
      form. G protein knockdown studies suggested that the Homer1 induction, but not
      the regulated splicing, was Galphaq/11 dependent. Phosphorylation of the splicing
      regulator SRp20 was found to be induced by GnRH. SRp20 depletion attenuated the
      GnRH-induced increase in the Homer1a-to-Homer1b/c ratio and modulated the effects
      of GnRH on FSHbeta and LHbeta expression. Homer1 gene knockdown resulted in
      increased GnRH-induced FSHbeta and LHbeta transcript levels. Furthermore, splice
      form-specific reduction of Homer1b/c increased both FSHbeta and LHbeta mRNA
      induction, whereas reduction of Homer1a had the opposite effect on FSHbeta
      induction. These results indicate that the regulation of Homer1 splicing by GnRH
      contributes to gonadotropin gene control. 

PMID- 24591651
TI  - Delineating the structural blueprint of the pre-mRNA 3'-end processing machinery.
AB  - Processing of mRNA precursors (pre-mRNAs) by polyadenylation is an essential step
      in gene expression. Polyadenylation consists of two steps, cleavage and poly(A)
      synthesis, and requires multiple cis elements in the pre-mRNA and a megadalton
      protein complex bearing the two essential enzymatic activities. While genetic and
      biochemical studies remain the major approaches in characterizing these factors,
      structural biology has emerged during the past decade to help understand the
      molecular assembly and mechanistic details of the process. With structural
      information about more proteins and higher-order complexes becoming available, we
      are coming closer to obtaining a structural blueprint of the polyadenylation
      machinery that explains both how this complex functions and how it is regulated
      and connected to other cellular processes. 

PMID- 24591655
TI  - The European Respiratory Review: meeting expectations of respiratory physicians
      through diversity and quality.

PMID- 24591654
TI  - CLOCK-controlled polyphonic regulation of circadian rhythms through canonical and
      noncanonical E-boxes.
AB  - In mammalian circadian clockwork, the CLOCK-BMAL1 complex binds to DNA enhancers
      of target genes and drives circadian oscillation of transcription. Here we
      identified 7,978 CLOCK-binding sites in mouse liver by chromatin
      immunoprecipitation-sequencing (ChIP-Seq), and a newly developed bioinformatics
      method, motif centrality analysis of ChIP-Seq (MOCCS), revealed a genome-wide
      distribution of previously unappreciated noncanonical E-boxes targeted by CLOCK.
      In vitro promoter assays showed that CACGNG, CACGTT, and CATG(T/C)G are
      functional CLOCK-binding motifs. Furthermore, we extensively revealed
      rhythmically expressed genes by poly(A)-tailed RNA-Seq and identified 1,629 CLOCK
      target genes within 11,926 genes expressed in the liver. Our analysis also
      revealed rhythmically expressed genes that have no apparent CLOCK-binding site,
      indicating the importance of indirect transcriptional and posttranscriptional
      regulations. Indirect transcriptional regulation is represented by rhythmic
      expression of CLOCK-regulated transcription factors, such as Kruppel-like factors
      (KLFs). Indirect posttranscriptional regulation involves rhythmic microRNAs that
      were identified by small-RNA-Seq. Collectively, CLOCK-dependent direct
      transactivation through multiple E-boxes and indirect regulations polyphonically
      orchestrate dynamic circadian outputs. 

PMID- 24591656
TI  - Evolvement of best practice in diagnosis and management of idiopathic pulmonary
      fibrosis.

PMID- 24591657
TI  - Breathing for two: pregnancy, asthma and respiratory failure.

PMID- 24591658
TI  - Allergic aspergillosis of the respiratory tract.

PMID- 24591659
TI  - Towards personalised therapy for lymphangioleiomyomatosis: lessons from cancer.
AB  - Lymphangioleiomyomatosis (LAM) is a rare cystic, destructive lung disease
      occurring almost exclusively in females. Bi-allelic inactivating tuberous
      sclerosis complex (TSC) gene mutations occur in LAM cells, resulting in
      activation of the mTORC1 pathway. Pivotal clinical trials have demonstrated that
      inhibition of mTORC1 with sirolimus can induce a partial response of TSC
      associated tumours and decrease the rate of lung function decline in females with
      LAM. Many parallels have been identified between LAM pathogenesis and neoplasia.
      Here, we highlight three key nodes through which advances in cancer therapy can
      streamline future innovation in clinical LAM research with parallels to breast
      and prostate cancer. These include: 1) hormonally targeted therapies to achieve
      true disease-free complete remissions; 2) the use of vascular endothelial growth
      factor-D and other plasma biomarkers to streamline early-phase clinical trials;
      and 3) the utilisation of histological and molecular features of biopsy material
      to enable patient stratification and personalised therapies. 

PMID- 24591660
TI  - Tuberculosis.
AB  - This article reviews the published literature on tuberculosis from September 2012
      to August 2013 and describes important advances in tuberculosis epidemiology,
      microbiology, pathology, clinical pharmacology, genetics, treatment and
      prevention. 

PMID- 24591661
TI  - Interstitial lung disease.
AB  - Interstitial lung diseases are a group of diffuse parenchymal lung disorders
      associated with substantial morbidity and mortality. Knowledge achieved in recent
      years has resulted in the publication of the new classification of idiopathic
      interstitial pneumonias, according to which there are three groups: major, rare
      and unclassified. The novelty of the new classification comes from the fact that
      difficult to classify entities can be treated according to the disease behaviour
      classification. Idiopathic pulmonary fibrosis is the most lethal amongst the
      interstitial lung diseases and presents high heterogeneity in clinical behaviour.
      A number of biomarkers have been proposed in order to predict the course of the
      disease and group patients with the same characteristics in clinical trials.
      Early diagnosis and disease stratification is also important in the field of
      other interstitial lung diseases. 

PMID- 24591662
TI  - Pulmonary rehabilitation.
AB  - Pulmonary rehabilitation is a comprehensive intervention designed to improve the
      physical and psychological condition of people with chronic respiratory disease
      and promote the long-term adherence to health-enhancing behaviours. During the
      2013 European Respiratory Society Annual Congress in Barcelona, Spain, a Clinical
      Year in Review session was held focusing on the latest developments in pulmonary
      rehabilitation. This review summarises some of the main findings of peer-reviewed
      articles focusing on pulmonary rehabilitation that were published in the 12
      months prior to the 2013 Annual Congress. 

PMID- 24591663
TI  - Asthma in pregnancy: a hit for two.
AB  - Asthma commonly occurs in pregnant females, and recent data have outlined the
      risks of adverse perinatal outcomes among this population. There is an increased
      risk of low birth weight and small for gestational age, particularly among
      females with moderate-to-severe asthma and exacerbations during pregnancy. There
      is also an increased risk of preterm birth, especially with oral steroid use, a
      small but statistically significant increased risk of congenital malformations,
      particularly of cleft lip with or without cleft palate, and an increased risk of
      neonatal hospitalisation and death. Active management may reduce these risks,
      possibly through reductions in exacerbations. Additional reassuring data have
      been presented for asthma medication use, which support the benefits outweighing
      the risks of indicated asthma medication use in pregnancy. Viral infections are
      an important trigger of asthma exacerbations in pregnancy, and recent data
      provides possible immunological changes that may explain this. Poor medication
      adherence despite worsening asthma symptoms in pregnancy is a problem which
      continues to be demonstrated in the literature. Improving asthma control in
      pregnancy has the potential to improve not only the mother's health but also that
      of her child. 

PMID- 24591664
TI  - Updates in oncology.
AB  - The objective of this review is to report the Clinical Year in Review proceedings
      in the field of thoracic oncology that were presented at the 2013 European
      Respiratory Society Annual Congress in Barcelona, Spain. Various topics were
      reviewed, including: epidemiology, screening, histology, and treatment of
      nonsmall cell lung cancer and small cell lung cancer. 

PMID- 24591665
TI  - Therapeutic options targeting angiogenesis in nonsmall cell lung cancer.
AB  - There is a major unmet medical need for effective and well-tolerated treatment
      options for patients with advanced nonsmall cell lung cancer (NSCLC), in both
      first-line and relapsed/refractory settings. Experimental evidence has validated
      signalling pathways that regulate tumour angiogenesis, including the vascular
      endothelial growth factor (VEGF), platelet-derived growth factor (PDGF) and
      fibroblast growth factor (FGF) pathways, as valid anti-cancer drug targets.
      However, to date, bevacizumab (an anti-VEGF monoclonal antibody) is the only
      antiangiogenic agent to be approved for the treatment of NSCLC. Many other
      agents, including antibodies, small-molecule tyrosine kinase inhibitors and
      vascular disrupting agents, have been assessed in phase III trials but have
      generally failed to demonstrate clinically meaningful benefits. This lack of
      success probably reflects the redundancy of proangiogenic pathways and the
      molecular and clinical heterogeneity of NSCLC. In this review we summarise
      recently completed and ongoing randomised clinical trials of emerging
      antiangiogenic agents in patients with NSCLC. We highlight recent promising data
      with agents that simultaneously inhibit multiple proangiogenic pathways,
      including the PDGF and FGF pathways, as well as the VEGF pathway. Finally, we
      discuss the outlook for antiangiogenic agents in NSCLC, emphasising the need for
      clinically validated prognostic and predictive biomarkers to identify patients
      most likely to respond to therapy. 

PMID- 24591667
TI  - Neglected evidence in idiopathic pulmonary fibrosis and the importance of early
      diagnosis and treatment.
AB  - In idiopathic pulmonary fibrosis (IPF), some facts or concepts based on
      substantial evidence, whilst implicit for learned subspecialists, have previously
      been neglected and/or not explicitly formulated or made accessible to a wider
      audience. IPF is strongly associated with cigarette smoking and is predominantly
      a disease of ageing. However, its cause(s) remain elusive and, thus, it is one of
      the most challenging diseases for the development of novel effective and safe
      therapies. With the approval of pirfenidone for patients with mild-to-moderate
      IPF, an earlier diagnosis of IPF is a prerequisite for earlier treatment and,
      potentially, improvement of the long-term clinical outcome of this progressive
      and ultimately fatal disease. An earlier diagnosis may be achieved in IPF by
      promoting thin-slice chest high-resolution computed tomography screening of
      interstitial lung disease as a "by-product" of large-scale lung cancer screening
      strategies in smokers, but other techniques, which have been neglected in the
      past, are now available. Lung auscultation and early identification of "velcro"
      crackles has been proposed as a key component of early diagnosis of IPF. An
      ongoing study is exploring correlations between lung sounds on auscultation
      obtained using electronic stethoscopes and high-resolution computed tomography
      patterns. 

PMID- 24591666
TI  - First-line treatment of EGFR-mutated nonsmall cell lung cancer: critical review
      on study methodology.
AB  - Recent advances in understanding the mechanisms of nonsmall cell lung cancer
      (NSCLC) has led to the development of targeted treatments, including the
      reversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors
      gefitinib and erlotinib, and the irreversible ErbB family blocker afatinib.
      Several important activating EGFR mutations have now been identified, which
      correlate strongly with response to treatment with these agents. Multiple
      randomised controlled trials have confirmed the association between the presence
      of activating EGFR mutations and objective response to gefitinib, erlotinib and
      afatinib, thus demonstrating their superiority over platinum-based chemotherapy
      as first-line treatment for NSCLC patients with EGFR mutation-positive tumours,
      and resulting in approval of these agents for use in this setting. It can be
      tempting to compare outcome data across multiple clinical trials and agents;
      however, substantial differences in methodology between studies, including
      investigator versus independent assessment and differences in patient
      eligibility, makes such comparisons fraught with difficulty. This critical review
      provides an overview of the evolution of the methodology used in eight phase III
      trials investigating first-line targeted treatment of NSCLC, identifies key
      differences in methodology and reporting, and critically assesses how these
      differences should be taken into account when interpreting the findings from such
      trials. 

PMID- 24591668
TI  - Pirfenidone: an update on clinical trial data and insights from everyday
      practice.
AB  - Pirfenidone is an orally active, small molecule that inhibits synthesis of
      profibrotic and inflammatory mediators. It was approved for the treatment of
      adults with mild-to-moderate idiopathic pulmonary fibrosis in the European Union
      based on the results of two pivotal phase III, double-blind, randomised, placebo
      controlled clinical trials (CAPACITY) demonstrating efficacy and safety, and
      supported by two Japanese clinical trials (SP2 and SP3). Currently, there is
      increasing interest in experience with pirfenidone in patients relating to the
      real-world setting. Following the publication of the CAPACITY clinical studies,
      additional analyses have been conducted to provide further support for
      pirfenidone in clinical practice, including a modified per-protocol analysis of
      the CAPACITY study population. New data from the RECAP extension study also
      provided longer term data for pirfenidone and promising continuation rates with
      treatment. Pirfenidone is also being evaluated in specialist centre cohorts
      providing important information on real-world efficacy and safety. Increasing
      experience with pirfenidone in everyday clinical practice is helping to establish
      ?expert guidance on the management of known adverse events, together with
      practical recommendations, to ensure adherence to treatment so that the possible
      longer term benefits of pirfenidone treatment in reducing lung function decline
      can be maximised. 

PMID- 24591669
TI  - Tissue remodelling in chronic bronchial diseases: from the epithelial to
      mesenchymal phenotype.
AB  - Airway remodelling is a critical feature of chronic bronchial diseases,
      characterised by aberrant repair of the epithelium and accumulation of
      fibroblasts, which contribute to extracellular matrix (ECM) deposition resulting
      in fixed bronchial obstruction. Recently, epithelial-mesenchymal transition (EMT)
      has been identified as a new source of fibroblasts that could contribute to the
      remodelling of the airways. This phenomenon consists of the loss of the
      epithelial phenotype by bronchial epithelial cells and the acquisition of a
      mesenchymal phenotype. These cells are then able to migrate and secrete ECM
      molecules. Herein, we review the different types of EMT. We will then focus on
      the signalling pathways that are involved, such as transforming growth factor
      beta and Wnt, as well as the more recently described Sonic Hedgehog pathway.
      Finally, we will highlight the implication of EMT in airway remodelling in
      specific chronic bronchial pathologies, such as asthma, chronic obstructive
      pulmonary disease and bronchiolitis obliterans following lung transplantation.
      Despite the limitations of in vitro models, future studies of EMT in vivo are
      warranted to shed new light on the pathomechanisms of bronchial obstruction. 

PMID- 24591670
TI  - Comorbidities in patients with COPD and pulmonary rehabilitation: do they matter?
AB  - It is now recognised that chronic obstructive pulmonary disease (COPD) is a
      heterogeneous disease with many systemic features. Cardiovascular, metabolic,
      musculoskeletal and psychological comorbidities contribute to the morbidity and
      mortality in all stages of the disease. The presence of comorbid conditions has
      important consequences for disease assessment and management. In addition to
      treatment of the structural and functional changes in the lungs, clinical
      programmes for COPD should also assess and manage patients' comorbidities. Thus,
      there is an increasing need to understand the interaction between existing
      therapies and comorbidities. Pulmonary rehabilitation is an evidence-based
      intervention that has been shown to improve clinical outcomes in COPD. However,
      the impact of comorbidities on outcomes of pulmonary rehabilitation and vice
      versa is only partially understood. To date, there is limited information on the
      need for adapting specific interventions in pulmonary rehabilitation to
      comorbidities or the potential adverse effects of pulmonary rehabilitation in
      these patients. This article addresses the currently available literature and
      suggests novel areas for research. 

PMID- 24591671
TI  - Successful use of noninvasive ventilation in pregnancy.

PMID- 24591672
TI  - Sudden death in a young male with a recent pneumothorax: a case report.

PMID- 24591673
TI  - Pulmonary arterial hypertension preceding idiopathic pulmonary fibrosis in a
      BMPR2 mutation positive patient.

PMID- 24591675
TI  - A rare case of scimitar syndrome with horseshoe lung.

PMID- 24591674
TI  - Pulse methylprednisolone in allergic bronchopulmonary aspergillosis
      exacerbations.

PMID- 24591676
TI  - Transvenous permanent pacemaker implantation in dextrocardia: technique,
      challenges, outcome, and a brief review of literature.
AB  - AIMS: Dextrocardia is a rare congenital anomaly. Pacemaker implantation in
      dextrocardia can be challenging because of the distorted anatomy and associated
      anomalies. The literature regarding implantation of pacemaker in dextrocardia is
      scarce. METHODS AND RESULTS: The study involved retrospective analysis of records
      of patients with dextrocardia who had undergone pacemaker implantation between
      January 2006 and July 2013 from a single centre. Six patients with dextrocardia
      (five males and one female) underwent permanent pacemaker implantation (PPI)
      between January 2006 and July 2013. Of them, three had situs solitus dextrocardia
      and three situs inversus dextrocardia. All three patients with situs solitus
      dextrocardia had associated corrected transposition of great arteries. The
      indication for pacemaker implantation was symptomatic complete atrioventricular
      (AV) block in four, high-grade AV block in one, and sinus node dysfunction in one
      patient. A favourable outcome was noted during a mean follow-up of 3.9 years (4
      months to 7 years) with one patient needing a pulse generator replacement.
      CONCLUSION: Permanent pacemaker implantation in dextrocardia can be challenging
      because of the distorted anatomy. Use of a technique employing angiography to
      delineate chamber anatomy and relationship can assist the operator during such
      difficult PPIs. The medium- and long-term survival after a successful pacemaker
      implantation in dextrocardia is favourable.

PMID- 24591677
TI  - Exercise-induced right bundle branch block progressive resolution.

PMID- 24591678
TI  - Catheter ablation of atrial fibrillation and left atrial flutter in a patient
      with a left atrial appendage occlusion device.

PMID- 24591679
TI  - Idiopathic ventricular fibrillation triggered by two distinct foci.

PMID- 24591680
TI  - A guide to understanding polycystic ovary syndrome (PCOS).
AB  - Polycystic ovary syndrome (PCOS) is the commonest endocrine disorder affecting
      women of reproductive age. Some 20% of women will have polycystic ovaries on an
      ultrasound scan and around 7% of women have the additional clinical or
      biochemical features of PCOS. As a complex multisystem disorder its background
      can be confusing to understand. They key feature, however, is an increased
      production of androgen by the ovaries. This review uses ovarian biology to
      describe a strategy to aid understanding and explanation of PCOS. This framework
      can be also be used to teach about PCOS and to inform different approaches to its
      management. 

PMID- 24591681
TI  - Emergency intrauterine device insertion in teenagers: an informal retrospective
      study.
AB  - BACKGROUND: Widespread and increased availability of oral emergency contraception
      (EC) over the past 10 years has made little difference to rates of unintended
      pregnancy, abortion and repeat abortion amongst teenagers. The insertion of an
      intrauterine device for EC (EC-IUD) is 98-99% effective compared with 85% for
      oral methods and can be used for ongoing, long-term reversible contraception.
      However this method is seldom used for teenagers, a group with a high risk of
      unintended pregnancy, and there is little published data on the use of EC-IUD in
      this group. METHODS: An anonymous case note review of EC-IUD use in teenagers in
      three centres in the UK was conducted to quantify provision, to identify
      insertion difficulties and short-term complications and to ascertain compliance
      with national guidance concerning sexually transmitted infection (STI) risk
      assessment and prophylaxis. RESULTS: A total of 103 cases was identified over 4
      years (2007-2010) from the three centres (London, Liverpool and Aberdeen). The
      results show that the majority of fittings were straightforward (94%) with few
      complications. Antibiotic prophylaxis was deemed necessary in 64% of attenders.
      CONCLUSIONS: The authors recommend that with STI screening and appropriate
      antibiotic prophylaxis, use of IUDs in women under the age of 20 years should be
      unrestricted both for long-term contraception and for EC.

PMID- 24591682
TI  - Patients' attitudes and experiences of relational continuity in semi-urban
      general practices in Oman.
AB  - BACKGROUND: Relational continuity is a cornerstone of primary care. In developing
      countries, however, little research has been conducted to determine the
      perception and experiences of patients in view of relational continuity in
      primary care. OBJECTIVE: To study the role of relational continuity in primary
      care settings and its effect on patients' perceptions and experiences. METHODS: A
      questionnaire-based survey was conducted at eight primary care health centres
      (PCHCs) in Al-Seeb province, Muscat, the capital city of Oman. All Omani patients
      aged 18 years and above attending their PCHCs during the study period were
      invited to participate in the study. RESULTS: From a total of 1300 patients
      invited, 958 Omani patients agreed to participate in the study (response rate =
      74%). More than half of the patients (61%) expressed the preference of consulting
      the same primary care physician (PCP) to whom they were accustomed. This
      increased to 69% if the patients had psychosocial problems and to 71% if the
      patients had chronic medical conditions. A significant proportion of the
      respondents (72%) felt comfortable and relaxed when consulting the same PCP and
      67% expressed an interest in maintaining continuity with the same PCP. The
      general perspective held by the majority of the studied patients (61%) indicated
      that relational continuity improved both the patients' medical conditions (51%)
      and the quality of services (61%). In actuality, however, only 18% experienced
      relational continuity in their PCHCs. The preference for relational continuity
      was significantly increased among patients who identified a favourite PCP (P =
      0.029) and among educated patients (P = 0.023). CONCLUSION: Although it is
      relatively difficult to consult with the same PCP, the majority of Omani patients
      have experienced several benefits from relational continuity within the context
      of patient-physician relationship. The preference for relational continuity was
      highly expressed by patients with chronic or psychosocial problems, patients who
      were educated and those who identified a named PCP. In view of these findings,
      the basis of relational continuity if progressed, a great effort is needed to
      develop and implement strategies to promote relational continuity in primary
      health care in Oman.

PMID- 24591683
TI  - Prospective study of a Swedish infertile cohort 2005-08: population
      characteristics, treatments and pregnancy rates.
AB  - BACKGROUND: We here report on results from a prospective study comprising 380
      infertile couples undergoing infertility work-up and various treatments for
      infertility in our clinic. The aim was to investigate the overall birth rate as a
      result of different treatments, as well as spontaneous pregnancies. METHODS:
      Three hundred and eighty couples were consecutively included between December
      2005 and May 2008. All couples underwent a fertility work-up, including
      hysterosalpingogram, hormonal characterization, clinical examination, screening
      for infectious diseases and semen analysis. The mean age of the women at the time
      of inclusion was 33.2 years. The mean duration of infertility prior to inclusion
      was 1.8 years. And 46.6% (n = 177) of the women had been pregnant prior to their
      first visit to the clinic and 30.0% (n = 114) had been pregnant earlier in their
      present relationship. RESULTS: As of November 2010, 57.3% (n = 218) of the women
      had given birth to a child when they were lost to follow up by the study.
      Spontaneous conception was observed in 11.3% (n = 43) of the women, 14.5% (n =
      64) conceived after intrauterine insemination (IUI), 4.2% (n = 16) conceived
      after ovarian hyperstimulation and ovulation induction (OH/OI) and 28.4% (n =
      113) after in vitro fertilization. There were 280 pregnancies and 58 spontaneous
      abortions (22.3%) in the group. Mean anti-mullerian hormone significantly
      correlated with antral follicle count and age and was significantly higher in the
      subgroup that became pregnant after IUI. CONCLUSIONS: Spontaneous pregnancies and
      IUI + OH/OI contributed significantly to the pregnancies observed in the total
      population. Predictive factors for pregnancy were anti-mullerian hormone in the
      group undergoing IUI treatment and in the age group >=38-duration of infertility.
      Previous pregnancies, body mass index, estradiol, follicle stimulating hormone or
      having given birth prior to the infertility period were not predictive of
      pregnancy for the infertile couples in this study.

PMID- 24591684
TI  - Measurement of intracellular Ca2+ release in intact and permeabilized cells using
      45Ca2+.
AB  - Ca(2+) is an important ion that controls almost every function in a cell.
      Activator Ca(2+) can be released from intracellular Ca(2+) stores, and there are
      various ways to study this release. Here, we introduce a technique that uses
      radioactive (45)Ca(2+) to quantitatively measure the unidirectional release of
      Ca(2+) from the nonmitochondrial Ca(2+) stores in monolayers of cultured cells.
      This technique can be used in cells with an intact plasma membrane as well as in
      cells in which the plasma membrane has been permeabilized. 

PMID- 24591685
TI  - Transposon insertional mutagenesis models of cancer.
AB  - Transposon-based insertional mutagenesis in the mouse provides a powerful
      approach for identifying new cancer genes. Transposon insertions in cancer genes
      are selected during tumor development because of their positive effect on tumor
      growth, and the transposon insertion sites in tumors thus serve as tags for
      identifying new cancer genes. Direct comparisons of transposon-mutated genes in
      mouse tumors with mutated genes in human tumors can lend insight into the genes
      and signaling pathways that drive tumorigenesis. This is critical for
      prioritizing genes for further study, either for their efficacy as biomarkers or
      drug targets. In this article, we will introduce DNA transposon-based systems
      used for gene discovery in mice and discuss their application to identify
      candidate cancer genes in light of recently published tumor studies. 

PMID- 24591687
TI  - Measurement of intracellular Ca2+ release in intact cells using 45Ca2+.
AB  - This protocol describes a technique using (45)Ca(2+) to measure the release of
      Ca(2+) from the intracellular stores in monolayers of intact cells cultured in 12
      well 4-cm(2) clusters. The (45)Ca(2+)-flux technique described here can only be
      applied to cell types that adhere to plastic. We describe the loading of the
      stores with (45)Ca(2+), and the subsequent (45)Ca(2+) efflux. 

PMID- 24591686
TI  - Measurement of intracellular Ca2+ release in permeabilized cells using 45Ca2+.
AB  - This protocol describes a technique to measure Ca(2+) release from the
      nonmitochondrial intracellular Ca(2+) stores in monolayers of saponin
      permeabilized cells cultured in 12-well 4-cm(2) clusters. The (45)Ca(2+)-flux
      technique described here can only be applied to cell types that still adhere to
      the plastic after exposing them to saponin. We describe the permeabilization
      procedure, the loading of the nonmitochondrial Ca(2+) stores with (45)Ca(2+), and
      the subsequent (45)Ca(2+) efflux. 

PMID- 24591688
TI  - Producing and concentrating lenti-Cre for mouse infections.
AB  - Lentiviral vectors offer versatility as vehicles for gene delivery. They can
      transduce a wide range of cell types and integrate into the host genome, which
      results in long-term expression of the transgene (Cre) both in vitro and in vivo.
      This protocol describes how lentiviral particles are produced, purified, and
      concentrated. 

PMID- 24591689
TI  - In vivo delivery of lenti-Cre or adeno-Cre into mice using intranasal
      instillation.
AB  - Lung cancer remains the leading cause of cancer deaths among both men and women,
      with a lower rate of survival than both breast and prostate cancer. Development
      of the Cre/lox system and improved mouse models have allowed researchers to gain
      a better understanding of human disease, including lung cancer. Through the viral
      delivery of Cre, gene function in adult mice can be precisely studied at a
      specific developmental stage or in a specific cell/tissue type of choice. This
      protocol describes how to produce adenovirus-Cre precipitate. Using this adeno
      Cre (or lentivirus-Cre), Cre can be expressed in mouse lungs. The virus is
      delivered by intranasal instillation. 

PMID- 24591690
TI  - Induction of germline apoptosis in Caenorhabditis elegans.
AB  - RNA interference (RNAi) is an incredibly powerful tool for rapid and efficient
      knockdown of gene expression. This technology can be used to induce apoptosis in
      the germline of Caenorhabditis elegans. Genotoxic stressors such as ionizing
      radiation (IR), ultraviolet light, chemical mutagens (e.g., N-ethyl-N-nitrosourea
      [ENU]), and DNA cross-linking reagents can also be used to stimulate apoptosis.
      These approaches, described here, combined with the powers of in vivo imaging
      methods, should keep C. elegans apoptosis researchers busy for several years,
      sorting out how various signaling pathways influence life and death decisions in
      this organism. 

PMID- 24591691
TI  - Visualizing apoptosis in embryos and the germline of Caenorhabditis elegans.
AB  - Visualizing apoptosis in developing embryos or the germline of Caenorhabditis
      elegans is remarkably easy because of the transparency of the organism. The
      invariant pattern of cell division and programmed cell death during development
      makes it possible to quantify small but reproducible changes in apoptosis, which
      are easy to detect by light microscopy because of the refractile properties of
      dying cells. Although apoptotic death is easy to visualize and quantify in the
      germline of adult hermaphrodites, the pattern of cell death is variable,
      especially when triggered by stress. The most convenient method for visualization
      of apoptosis in vivo is light microscopy, which requires immobilizing live
      embryos or adult animals on slides. This protocol describes the basic methods for
      visualizing and analyzing apoptosis in living animals. 

PMID- 24591692
TI  - Simultaneous patch-clamping and calcium imaging in developing dendrites.
AB  - Calcium imaging has been used extensively to explore the role of action potential
      (AP) firing in the development of neuronal structure and synaptic function
      because increases in intracellular calcium ([Ca(2+)]i) reliably and, within a
      certain range, linearly reflect neuronal spiking activity. Patterns of APs in
      individual cells can be deduced from calcium recordings, which have typically
      been performed at the level of cell bodies. However, neurons are particularly
      susceptible to phototoxicity when they are illuminated at the soma. Furthermore,
      for some imaging experiments (e.g., those that address the interactions between
      dendrites and axons during synapse formation), the cell body of a given neuron
      may simply not be in the field of view. In these situations, it would be helpful
      to determine the spiking patterns of a neuron from the calcium activity in its
      subcellular compartments such as stretches of dendrites or axons. Here, we
      describe an approach for determining the relationship between AP firing and
      dendritic calcium transients by simultaneously imaging calcium transients in
      small dendritic stretches of hippocampal pyramidal neurons in slice cultures from
      neonatal rats and recording spiking activity with whole-cell patch-clamp
      recordings in these neurons. These experiments allow us to correlate the
      electrophysiological spiking pattern with the accompanying changes in the calcium
      concentration in individual dendritic segments. 

PMID- 24591693
TI  - Preparation of ribonucleoprotein-enriched nucleoplasmic extracts from Drosophila
      cells.
AB  - Here we describe how to prepare nucleoplasmic extracts from suspension cultures
      of Drosophila S2 (Schneider Line 2) cells. Harvested cells are washed in
      phosphate-buffered saline supplemented with MgCl2, resuspended in hypotonic
      buffer, and homogenized. Nuclei are isolated by centrifugation and then
      sonicated. The nuclear sonicate is placed on a 30% sucrose cushion and
      sedimented. The soluble nuclear ribonucleoprotein (RNP) complexes remain in the
      supernatant and the nuclear membrane fragments and chromatin pellet through the
      sucrose cushion. 

PMID- 24591694
TI  - Large-scale immunopurification of ribonucleoprotein complexes from Drosophila
      nucleoplasmic extracts for tiling microarrays.
AB  - It is of interest to be able to define sets of cellular RNAs associated with
      specific RNA-binding proteins. This "guilt by association" can lead to new
      insights into how RNA-binding proteins modulate posttranscriptional gene
      expression of specific target RNAs. To identify these RNAs, antibodies against
      RNA-binding proteins can be used to immunopurify endogenous RNA-protein complexes
      from cells, and then the associated RNAs can be characterized. The method
      described here was developed to identify binding regions on nuclear transcripts
      for Drosophila heterogeneous nuclear ribonucleoproteins (hnRNPs). An antibody is
      added to an RNP extract and incubated to allow antigen-antibody complexes to
      form. The antibody-antigen complexes are then retrieved by binding of the
      antibody constant region to staphylococcal Protein A immobilized on Sepharose
      beads. The bead-immobilized complexes are then washed and RNA is prepared. The
      RNA is used to generate random-primed cDNA, cRNA, and biotinlyated cDNA probes
      for use on Affymetrix whole-genome Drosophila tiling arrays. 

PMID- 24591695
TI  - Spectral methods for functional brain imaging.
AB  - Dynamic functional imaging experiments typically generate large, multivariate
      data sets that contain considerable spatial and temporal complexity. The goal of
      this introduction is to present signal-processing techniques that allow the
      underlying spatiotemporal structure to be readily distilled and that also enable
      signal versus noise contributions to be separated. 

PMID- 24591696
TI  - Calcium imaging in the intact olfactory system of zebrafish and mouse.
AB  - Odors are first detected by olfactory sensory neurons (OSNs) and evoke stimulus
      specific patterns of activation across the input channels of the olfactory bulb
      (OB), the glomeruli. The output of the OB consists of spatiotemporal activity
      patterns across mitral/tufted cells that are conveyed to multiple pallial and
      subpallial target areas. In the main olfactory system of vertebrates, as well as
      in the olfactory system of insects, odor information is encoded by distributed
      patterns of activity across a large number of glomeruli or neurons. Ca(2+)
      imaging has therefore become an important approach used to analyse the encoding
      and processing of olfactory information by populations of glomeruli or neurons.
      Experiments in the intact olfactory system are important to maintain the
      integrity of the system, to analyse activity patterns evoked by natural odors,
      and to examine the influence of active sampling strategies, such as sniffing in
      mammals. This protocol focuses on how to visualize glomerular Ca(2+) signals
      after loading a dextran-coupled Ca(2+) indicator into OSNs. Separate procedures
      are described for zebrafish and mice. 

PMID- 24591697
TI  - Calcium imaging in populations of olfactory neurons by planar illumination
      microscopy.
AB  - Neurons in the olfactory system display extraordinary functional diversity, which
      at the level of sensory neurons arises from the expression of one out of several
      hundred distinct receptor types. To cope with this diversity, one approach is to
      use techniques that can record sensory responses from many neurons
      simultaneously. We have developed a form of light-sheet microscopy, called
      objective-coupled planar illumination (OCPI) microscopy, that is well suited to
      recording at high signal-to-noise ratios from large neuronal populations. Because
      OCPI microscopy illuminates the entire field simultaneously, it allows fast
      imaging without compromising field of view. At current camera speeds, pixels can
      be acquired more than 100-fold faster than by point-scanning fluorescence
      microscopy. Here we describe the theory, advantages, and practical implementation
      of planar illumination and briefly discuss its application to neuronal recording
      in the mouse vomeronasal organ. We also provide a brief protocol, in which a
      mouse is pretreated with dye for 1 wk to allow labeling of the sensory neurons
      before stimulation and imaging. 

PMID- 24591698
TI  - Central neural mechanisms of interindividual difference in discomfort during
      sensorimotor incongruence in healthy volunteers: an experimental study.
AB  - OBJECTIVES: It has been reported that disturbance in sensory and motor function
      may induce sensorimotor incongruence and produce pain, discomfort and other
      sensations in healthy volunteers. One study suggested that sensorimotor
      incongruent information to healthy subjects results in increased neuronal
      activity in the posterior parietal cortex (PPC) and dorsolateral prefrontal
      cortex; however, this study did not take into consideration the discomfort
      induced by sensorimotor incongruence. The present study attempted to characterize
      intracortical electrical activities for sensorimotor incongruence in the
      frequency domain. In our study, electroencephalogram (EEG) cortical sources were
      compared between sensorimotor congruence and sensorimotor incongruence. In
      addition, high and no discomfort subgroups were compared during sensorimotor
      incongruence. METHODS: Eighteen healthy female subjects participated in this
      study. Subjects were then asked to flex/extend both arms in a
      congruent/incongruent manner while viewing a whiteboard/mirror. EEG was performed
      to determine the cortical activation during sensorimotor congruence and
      incongruence. RESULTS: Alpha band activity in the right posterior parietal cortex
      during sensorimotor incongruence was significantly lower than that of
      sensorimotor congruence. The source activities induced in the anterior cingulate
      cortex (ACC) beta band activity and the posterior cingulate cortex (PCC) alpha
      band activity significantly decreased in the high-discomfort vs the no-discomfort
      subgroup. CONCLUSION: The present findings suggest that the ACC and PCC are more
      activated in the high-discomfort subgroup than in the no-discomfort subgroup
      during sensorimotor incongruence. This method may evaluate the effectiveness of
      new medication therapy and/or rehabilitation by assessing the difference in the
      neuronal activity of chronic patients before and after treatment.

PMID- 24591699
TI  - What should adult rheumatology know about paediatric rheumatology?

PMID- 24591700
TI  - Is there a best way to measure co-morbidity?

PMID- 24591702
TI  - MS-viewer: a web-based spectral viewer for proteomics results.
AB  - The sharing and viewing of peptide identification results from search engines
      analyzing mass-spectrometry-based proteomic data is made difficult by the range
      of analysis tools employed, in that each produces a different output format.
      Annotated results associated with a journal article often have to be made
      available, but providing these in a format that can be queried by other
      researchers is often difficult. This is because although standard formats for
      results have been developed, these are not necessarily easy to produce. In this
      manuscript we describe the MS-Viewer program, part of the Protein Prospector Web
      package, which uses easy-to-create tabular files as input for providing highly
      interactive viewing of search engine results. Thanks to the simplicity and
      flexibility of the input format, results from a wide variety of search engines
      have been successfully viewed through the Web interface of this tool. 

PMID- 24591703
TI  - Policymaking to preserve privacy in disclosure of public health data: a suggested
      framework.
AB  - Health organisations in Turkey gather a vast amount of valuable individual data
      that can be used for public health purposes. The organisations use rigid methods
      to remove some useful details from the data while publishing the rest of the data
      in a highly aggregated form, mostly because of privacy concerns and lack of
      standardised policies. This action leads to information loss and bias affecting
      public health research. Hence, organisations need dynamic policies and well
      defined procedures rather than a specific algorithm to protect the privacy of
      individual data. To address this need, we developed a framework for the
      systematic application of anonymity methods while reducing and objectively
      reporting the information loss without leaking confidentiality. This framework
      acts as a roadmap for policymaking by providing high-level pseudo-policies with
      semitechnical guidelines in addition to some sample scenarios suitable for
      policymakers, public health programme managers and legislators. 

PMID- 24591705
TI  - Impact of the isolation medium for detection of carbapenemase-producing
      Enterobacteriaceae using an updated version of the Carba NP test.

PMID- 24591706
TI  - Oral Candida carriage and immune status in Thai human immunodeficiency virus
      infected individuals.
AB  - Oral candidiasis is a common opportunistic infection among human immunodeficiency
      virus (HIV)-infected individuals, with growing concerns about the emergence of
      non-albicans species with resistance to antifungal agents. This cross-sectional
      study determined the prevalence of oral Candida species in Thai HIV-infected
      adults and factors affecting their colonization. Candida species were identified
      from oral rinse samples of 60 HIV-infected participants of the MTCT-Plus
      initiative and 49 healthy controls by culture-based and molecular assays. The
      prevalence of oral Candida carriage was similar in HIV-infected patients (56.6 %)
      and in controls (55.1 %, P = 0.87). Candida albicans was the most predominant
      species in both groups (94.1 % of Candida carriers in HIV, 88.9 % in control).
      Interestingly, Candida dubliniensis was the second most common species in
      controls (29.6 %) and the third in HIV-infected patients (11.8 %, P = 0.08).
      Multivariate analysis showed that, amongst HIV-infected individuals, CD4 count
      <200 cells mm(-3) was associated with increased prevalence of oral carriage of
      both C. albicans (P = 0.03) and non-albicans species (P = 0.03). Moreover,
      patients with tuberculosis infection had a higher prevalence of the non-albicans
      species than those without (P = 0.03). Intriguingly, contraceptive use was also
      associated positively with non-albicans and multi-species carriage (P = 0.04 for
      both). However, use of antiretroviral drugs protected the patients from Candida
      carriage (P = 0.03), especially from C. albicans (P = 0.02). In conclusion, while
      HIV-infected individuals had a similar prevalence of oral Candida carriage to
      that of the control group, host immune status, tuberculosis infection, and
      contraceptive use may influence oral colonization of Candida, especially of the
      non-albicans species.

PMID- 24591707
TI  - Changing the light environment: chloroplast signalling and response mechanisms.
AB  - Light is an essential environmental factor required for photosynthesis, but it
      also mediates signals to control plant development and growth and induces stress
      tolerance. The photosynthetic organelle (chloroplast) is a key component in the
      signalling and response network in plants. This theme issue of Philosophical
      Transactions of the Royal Society of London B: Biology provides updates,
      highlights and summaries of the most recent findings on chloroplast-initiated
      signalling cascades and responses to environmental changes, including light and
      biotic stress. Besides plant molecular cell biology and physiology, the theme
      issue includes aspects from the cross-disciplinary fields of environmental
      adaptation, ecology and agronomy. 

PMID- 24591708
TI  - On the origin of a slowly reversible fluorescence decay component in the
      Arabidopsis npq4 mutant.
AB  - Over-excitation of photosynthetic apparatus causing photoinhibition is
      counteracted by non-photochemical quenching (NPQ) of chlorophyll fluorescence,
      dissipating excess absorbed energy into heat. The PsbS protein plays a key role
      in this process, thus making the PsbS-less npq4 mutant unable to carry out qE,
      the major and most rapid component of NPQ. It was proposed that npq4 does perform
      qE-type quenching, although at lower rate than WT Arabidopsis. Here, we
      investigated the kinetics of NPQ in PsbS-depleted mutants of Arabidopsis. We show
      that red light was less effective than white light in decreasing maximal
      fluorescence in npq4 mutants. Also, the kinetics of fluorescence dark recovery
      included a decay component, qM, exhibiting the same amplitude and half-life in
      both WT and npq4 mutants. This component was uncoupler-sensitive and unaffected
      by photosystem II repair or mitochondrial ATP synthesis inhibitors. Targeted
      reverse genetic analysis showed that traits affecting composition of the
      photosynthetic apparatus, carotenoid biosynthesis and state transitions did not
      affect qM. This was depleted in the npq4phot2 mutant which is impaired in
      chloroplast photorelocation, implying that fluorescence decay, previously
      described as a quenching component in npq4 is, in fact, the result of decreased
      photon absorption caused by chloroplast relocation rather than a change in the
      activity of quenching reactions. 

PMID- 24591709
TI  - The relationship between maximum tolerated light intensity and photoprotective
      energy dissipation in the photosynthetic antenna: chloroplast gains and losses.
AB  - The principle of quantifying the efficiency of protection of photosystem II
      (PSII) reaction centres against photoinhibition by non-photochemical energy
      dissipation (NPQ) has been recently introduced by Ruban & Murchie (2012 Biochim.
      Biophys. Acta 1817, 977-982 (doi:10.1016/j.bbabio.2012.03.026)). This is based
      upon the assessment of two key parameters: (i) the relationship between the PSII
      yield and NPQ, and (ii) the fraction of intact PSII reaction centres in the dark
      after illumination. In this paper, we have quantified the relationship between
      the amplitude of NPQ and the light intensity at which all PSII reaction centres
      remain intact for plants with different levels of PsbS protein, known to play a
      key role in the process. It was found that the same, nearly linear, relationship
      exists between the levels of the protective NPQ component (pNPQ) and the
      tolerated light intensity in all types of studied plants. This approach allowed
      for the quantification of the maximum tolerated light intensity, the light
      intensity at which all plant leaves become photoinhibited, the fraction of (most
      likely) unnecessary or 'wasteful' NPQ, and the fraction of photoinhibited PSII
      reaction centres under conditions of prolonged illumination by full sunlight. It
      was concluded that the governing factors in the photoprotection of PSII are the
      level and rate of protective pNPQ formation, which are often in discord with the
      amplitude of the conventional measure of photoprotection, the quickly reversible
      NPQ component, qE. Hence, we recommend pNPQ as a more informative and less
      ambiguous parameter than qE, as it reflects the effectiveness and limitations of
      the major photoprotective process of the photosynthetic membrane. 

PMID- 24591710
TI  - Short-term acclimation of the photosynthetic electron transfer chain to changing
      light: a mathematical model.
AB  - Photosynthetic eukaryotes house two photosystems with distinct light absorption
      spectra. Natural fluctuations in light quality and quantity can lead to
      unbalanced or excess excitation, compromising photosynthetic efficiency and
      causing photodamage. Consequently, these organisms have acquired several distinct
      adaptive mechanisms, collectively referred to as non-photochemical quenching
      (NPQ) of chlorophyll fluorescence, which modulates the organization and function
      of the photosynthetic apparatus. The ability to monitor NPQ processes
      fluorometrically has led to substantial progress in elucidating the underlying
      molecular mechanisms. However, the relative contribution of distinct NPQ
      mechanisms to variable light conditions in different photosynthetic eukaryotes
      remains unclear. Here, we present a mathematical model of the dynamic regulation
      of eukaryotic photosynthesis using ordinary differential equations. We
      demonstrate that, for Chlamydomonas, our model recapitulates the basic
      fluorescence features of short-term light acclimation known as state transitions
      and discuss how the model can be iteratively refined by comparison with
      physiological experiments to further our understanding of light acclimation in
      different species. 

PMID- 24591711
TI  - Thioredoxin-dependent regulatory networks in chloroplasts under fluctuating light
      conditions.
AB  - Plants have adopted a number of mechanisms to restore redox homeostasis in the
      chloroplast under fluctuating light conditions in nature. Chloroplast thioredoxin
      systems are crucial components of this redox network, mediating environmental
      signals to chloroplast proteins. In the reduced state, thioredoxins control the
      structure and function of proteins by reducing disulfide bridges in the redox
      active site of a protein. Subsequently, an oxidized thioredoxin is reduced by a
      thioredoxin reductase, the two enzymes together forming a thioredoxin system.
      Plant chloroplasts have versatile thioredoxin systems, including two reductases
      dependent on ferredoxin and NADPH as reducing power, respectively, several types
      of thioredoxins, and the system to deliver thiol redox signals to the thylakoid
      membrane and lumen. Light controls the activity of chloroplast thioredoxin
      systems in two ways. First, light reactions activate the thioredoxin systems via
      donation of electrons to oxidized ferredoxin and NADP(+), and second, light
      induces production of reactive oxygen species in chloroplasts which deactivate
      the components of the thiol redox network. The diversity and partial redundancy
      of chloroplast thioredoxin systems enable chloroplast metabolism to rapidly
      respond to ever-changing environmental conditions and to raise plant fitness in
      natural growth conditions. 

PMID- 24591712
TI  - Structural changes of the thylakoid membrane network induced by high light stress
      in plant chloroplasts.
AB  - Land plants live in a challenging environment dominated by unpredictable changes.
      A particular problem is fluctuation in sunlight intensity that can cause
      irreversible damage of components of the photosynthetic apparatus in thylakoid
      membranes under high light conditions. Although a battery of photoprotective
      mechanisms minimize damage, photoinhibition of the photosystem II (PSII) complex
      occurs. Plants have evolved a multi-step PSII repair cycle that allows efficient
      recovery from photooxidative PSII damage. An important feature of the repair
      cycle is its subcompartmentalization to stacked grana thylakoids and unstacked
      thylakoid regions. Thus, understanding the crosstalk between stacked and
      unstacked thylakoid membranes is essential to understand the PSII repair cycle.
      This review summarizes recent progress in our understanding of high-light-induced
      structural changes of the thylakoid membrane system and correlates these changes
      to the efficiency of the PSII repair cycle. The role of reversible protein
      phosphorylation for structural alterations is discussed. It turns out that
      dynamic changes in thylakoid membrane architecture triggered by high light
      exposure are central for efficient repair of PSII. 

PMID- 24591713
TI  - The functions of WHIRLY1 and REDOX-RESPONSIVE TRANSCRIPTION FACTOR 1 in cross
      tolerance responses in plants: a hypothesis.
AB  - Chloroplasts are important sensors of environment change, fulfilling key roles in
      the regulation of plant growth and development in relation to environmental cues.
      Photosynthesis produces a repertoire of reductive and oxidative (redox) signals
      that provide information to the nucleus facilitating appropriate acclimation to a
      changing light environment. Redox signals are also recognized by the cellular
      innate immune system allowing activation of non-specific, stress-responsive
      pathways that underpin cross tolerance to biotic-abiotic stresses. While these
      pathways have been intensively studied in recent years, little is known about the
      different components that mediate chloroplast-to-nucleus signalling and
      facilitate cross tolerance phenomena. Here, we consider the properties of the
      WHIRLY family of proteins and the REDOX-RESPONSIVE TRANSCRIPTION FACTOR 1 (RRTF1)
      in relation to chloroplast redox signals that facilitate the synergistic co
      activation of gene expression pathways and confer cross tolerance to abiotic and
      biotic stresses. We propose a new hypothesis for the role of WHIRLY1 as a redox
      sensor in chloroplast-to-nucleus retrograde signalling leading to cross
      tolerance, including acclimation and immunity responses. By virtue of its
      association with chloroplast nucleoids and with nuclear DNA, WHIRLY1 is an
      attractive candidate coordinator of the expression of photosynthetic genes in the
      nucleus and chloroplasts. We propose that the redox state of the photosynthetic
      electron transport chain triggers the movement of WHIRLY1 from the chloroplasts
      to the nucleus, and draw parallels with the regulation of NONEXPRESSOR OF
      PATHOGENESIS-RELATED GENES 1 (NPR1). 

PMID- 24591714
TI  - Singlet oxygen-mediated and EXECUTER-dependent signalling and acclimation of
      Arabidopsis thaliana exposed to light stress.
AB  - Plants respond to environmental changes by acclimation that activates defence
      mechanisms and enhances the plant's resistance against a subsequent more severe
      stress. Chloroplasts play an important role as a sensor of environmental stress
      factors that interfere with the photosynthetic electron transport and enhance the
      production of reactive oxygen species (ROS). One of these ROS, singlet oxygen
      ((1)O2), activates a signalling pathway within chloroplasts that depends on the
      two plastid-localized proteins EXECUTER 1 and 2. Moderate light stress induces
      acclimation protecting photosynthetic membranes against a subsequent more severe
      high light stress and at the same time activates (1)O2-mediated and EXECUTER
      dependent signalling. Pre-treatment of Arabidopsis seedlings with moderate light
      stress confers cross-protection against a virulent Pseudomonas syringae strain.
      While non-pre-acclimated seedlings are highly susceptible to the pathogen
      regardless of whether (1)O2- and EXECUTER-dependent signalling is active or not,
      pre-stressed acclimated seedlings without this signalling pathway lose part of
      their pathogen resistance. These results implicate (1)O2- and EXECUTER-dependent
      signalling in inducing acclimation but suggest also a contribution by other yet
      unknown signalling pathways during this response of plants to light stress. 

PMID- 24591715
TI  - Putative role of the malate valve enzyme NADP-malate dehydrogenase in H2O2
      signalling in Arabidopsis.
AB  - In photosynthetic organisms, sudden changes in light intensity perturb the
      photosynthetic electron flow and lead to an increased production of reactive
      oxygen species. At the same time, thioredoxins can sense the redox state of the
      chloroplast. According to our hypothesis, thioredoxins and related thiol reactive
      molecules downregulate the activity of H2O2-detoxifying enzymes, and thereby
      allow a transient oxidative burst that triggers the expression of H2O2 responsive
      genes. It has been shown recently that upon light stress, catalase activity was
      reversibly inhibited in Chlamydomonas reinhardtii in correlation with a transient
      increase in the level of H2O2. Here, it is shown that Arabidopsis thaliana
      mutants lacking the NADP-malate dehydrogenase have lost the reversible
      inactivation of catalase activity and the increase in H2O2 levels when exposed to
      high light. The mutants were slightly affected in growth and accumulated higher
      levels of NADPH in the chloroplast than the wild-type. We propose that the malate
      valve plays an essential role in the regulation of catalase activity and the
      accumulation of a H2O2 signal by transmitting the redox state of the chloroplast
      to other cell compartments. 

PMID- 24591716
TI  - Light-harvesting mutants show differential gene expression upon shift to high
      light as a consequence of photosynthetic redox and reactive oxygen species
      metabolism.
AB  - The amount of light energy that is harvested and directed to the photosynthetic
      machinery is regulated in order to control the production of reactive oxygen
      species (ROS) in leaf tissues. ROS have important roles as signalling factors
      that instigate and mediate a range of cellular responses, suggesting that the
      mechanisms regulating light-harvesting and photosynthetic energy transduction
      also affect cell signalling. In this study, we exposed wild-type (WT) Arabidopsis
      and mutants impaired in the regulation of photosynthetic light-harvesting (stn7,
      tap38 and npq4) to transient high light (HL) stress in order to study the role of
      these mechanisms for up- and downregulation of gene expression under HL stress.
      The mutants, all of which have disturbed regulation of excitation energy transfer
      and distribution, responded to transient HL treatment with surprising similarity
      to the WT in terms of general 'abiotic stress-regulated' genes associated with
      hydrogen peroxide and 12-oxo-phytodienoic acid signalling. However, we identified
      distinct expression profiles in each genotype with respect to induction of
      singlet oxygen and jasmonic acid-dependent responses. The results of this study
      suggest that the control of excitation energy transfer interacts with hormonal
      regulation. Furthermore, the photosynthetic pigment-protein complexes appear to
      operate as receptors that sense the energetic balance between the photosynthetic
      light reactions and downstream metabolism. 

PMID- 24591717
TI  - Interaction between plastid and mitochondrial retrograde signalling pathways
      during changes to plastid redox status.
AB  - Mitochondria and chloroplasts depend upon each other; photosynthesis provides
      substrates for mitochondrial respiration and mitochondrial metabolism is
      essential for sustaining photosynthetic carbon assimilation. In addition,
      mitochondrial respiration protects photosynthesis against photoinhibition by
      dissipating excess redox equivalents from the chloroplasts. Genetic defects in
      mitochondrial function result in an excessive reduction and energization of the
      chloroplast. Thus, it is clear that the activities of mitochondria and plastids
      need to be coordinated, but the manner by which the organelles communicate to
      coordinate their activities is unknown. The regulator of alternative oxidase
      (rao1) mutant was isolated as a mutant unable to induce AOX1a expression in
      response to the inhibitor of the mitochondrial cytochrome c reductase (complex
      III), antimycin A. RAO1 encodes the nuclear localized cyclin-dependent kinase E1
      (CDKE1). Interestingly, the rao1 mutant demonstrates a genome uncoupled phenotype
      also in response to redox changes in the photosynthetic electron transport chain.
      Thus, CDKE1 was shown to regulate both LIGHT HARVESTING COMPLEX B (LHCB) and
      ALTERNATIVE OXIDASE 1 (AOX1a) expression in response to retrograde signals. Our
      results suggest that CDKE1 is a central nuclear component integrating
      mitochondrial and plastid retrograde signals and plays a role in regulating
      energy metabolism during the response to stress. 

PMID- 24591718
TI  - Influence of plastids on light signalling and development.
AB  - In addition to their contribution to metabolism, chloroplasts emit signals that
      influence the expression of nuclear genes that contribute to numerous plastidic
      and extraplastidic processes. Plastid-to-nucleus signalling optimizes chloroplast
      function, regulates growth and development, and affects responses to
      environmental cues. An incomplete list of plastid signals is available and
      particular plastid-to-nucleus signalling mechanisms are partially understood. The
      plastid-to-nucleus signalling that depends on the GENOMES UNCOUPLED (GUN) genes
      couples the expression of nuclear genes to the functional state of the
      chloroplast. Analyses of gun mutants provided insight into the mechanisms and
      biological functions of plastid-to-nucleus signalling. GUN genes contribute to
      chloroplast biogenesis, the circadian rhythm, stress tolerance, light signalling
      and development. Some have criticized the gun mutant screen for employing
      inhibitors of chloroplast biogenesis and suggested that gun alleles do not
      disrupt significant plastid-to-nucleus signalling mechanisms. Here, I briefly
      review GUN-dependent plastid-to-nucleus signalling, explain the flaws in the
      major criticisms of the gun mutant screen and review the influence of plastids on
      light signalling and development. 

PMID- 24591719
TI  - Abscisic acid signalling determines susceptibility of bundle sheath cells to
      photoinhibition in high light-exposed Arabidopsis leaves.
AB  - The rapid induction of the bundle sheath cell (BSC)-specific expression of
      ASCORBATE PEROXIDASE2 (APX2) in high light (HL)-exposed leaves of Arabidopsis
      thaliana is, in part, regulated by the hormone abscisic acid (ABA) produced by
      vascular parenchyma cells. In this study, we provide more details of the ABA
      signalling that regulates APX2 expression and consider its importance in the
      photosynthetic responses of BSCs and whole leaves. This was done using a
      combination of analyses of gene expression and chlorophyll a fluorescence of both
      leaves and individual BSCs and mesophyll cells. The regulation of APX2 expression
      occurs by the combination of the protein kinase SnRK2.6 (OST1):protein
      phosphatase 2C ABI2 and a Galpha (GPA1)-regulated signalling pathway. The use of
      an ost1-1/gpa1-4 mutant established that these signalling pathways are distinct
      but interact to regulate APX2. In HL-exposed leaves, BSC chloroplasts were more
      susceptible to photoinhibition than those of mesophyll cells. The activity of the
      ABA-signalling network determined the degree of susceptibility of BSCs to
      photoinhibition by influencing non-photochemical quenching. By contrast, in HL
      exposed whole leaves, ABA signalling did not have any major influence on their
      transcriptomes nor on their susceptibility to photoinhibition, except where guard
      cell responses were observed. 

PMID- 24591720
TI  - Signalling crosstalk in light stress and immune reactions in plants.
AB  - The evolutionary history of plants is tightly connected with the evolution of
      microbial pathogens and herbivores, which use photosynthetic end products as a
      source of life. In these interactions, plants, as the stationary party, have
      evolved sophisticated mechanisms to sense, signal and respond to the presence of
      external stress agents. Chloroplasts are metabolically versatile organelles that
      carry out fundamental functions in determining appropriate immune reactions in
      plants. Besides photosynthesis, chloroplasts host key steps in the biosynthesis
      of amino acids, stress hormones and secondary metabolites, which have a great
      impact on resistance against pathogens and insect herbivores. Changes in
      chloroplast redox signalling pathways and reactive oxygen species metabolism also
      mediate local and systemic signals, which modulate plant resistance to light
      stress and disease. Moreover, interplay among chloroplastic signalling networks
      and plasma membrane receptor kinases is emerging as a key mechanism that
      modulates stress responses in plants. This review highlights the central role of
      chloroplasts in the signalling crosstalk that essentially determines the outcome
      of plant-pathogen interactions in plants. 

PMID- 24591721
TI  - Relaxation of the non-photochemical chlorophyll fluorescence quenching in
      diatoms: kinetics, components and mechanisms.
AB  - Diatoms are especially important microorganisms because they constitute the
      larger group of microalgae. To survive the constant variations of the light
      environment, diatoms have developed mechanisms aiming at the dissipation of
      excess energy, such as the xanthophyll cycle and the non-photochemical
      chlorophyll (Chl) fluorescence quenching. This contribution is dedicated to the
      relaxation of the latter process when the adverse conditions cease. An original
      nonlinear regression analysis of the relaxation of non-photochemical Chl
      fluorescence quenching, qN, in diatoms is presented. It was used to obtain
      experimental evidence for the existence of three time-resolved components in the
      diatom Phaeodactylum tricornutum: qNf, qNi and qNs. qNf (s time-scale) and qNs (h
      time-scale) are exponential in shape. By contrast, qNi (min time-scale) is of
      sigmoidal nature and is dominant among the three components. The application of
      metabolic inhibitors (dithiothreitol, ammonium chloride, cadmium and
      diphenyleneiodonium chloride) allowed the identification of the mechanisms on
      which each component mostly relies. qNi is linked to the relaxation of the
      DeltapH gradient and the reversal of the xanthophyll cycle. qNs quantifies the
      stage of photoinhibition caused by the high light exposure, qNf seems to reflect
      fast conformational changes within thylakoid membranes in the vicinity of the
      photosystem II complexes. 

PMID- 24591722
TI  - Photophysiology of kleptoplasts: photosynthetic use of light by chloroplasts
      living in animal cells.
AB  - Kleptoplasty is a remarkable type of photosynthetic association, resulting from
      the maintenance of functional chloroplasts--the 'kleptoplasts'--in the tissues of
      a non-photosynthetic host. It represents a biologically unique condition for
      chloroplast and photosynthesis functioning, occurring in different phylogenetic
      lineages, namely dinoflagellates, ciliates, foraminiferans and, most
      interestingly, a single taxon of metazoans, the sacoglossan sea slugs. In the
      case of sea slugs, chloroplasts from macroalgae are often maintained as
      intracellular organelles in cells of these marine gastropods, structurally intact
      and photosynthetically competent for extended periods of time. Kleptoplasty has
      long attracted interest owing to the longevity of functional kleptoplasts in the
      absence of the original algal nucleus and the limited number of proteins encoded
      by the chloroplast genome. This review updates the state-of-the-art on
      kleptoplast photophysiology, focusing on the comparative analysis of the
      responses to light of the chloroplasts when in their original, macroalgal cells,
      and when sequestered in animal cells and functioning as kleptoplasts. It covers
      fundamental but ecologically relevant aspects of kleptoplast light responses,
      such as the occurrence of photoacclimation in hospite, operation of
      photoprotective processes and susceptibility to photoinhibition. Emphasis is
      given to host-mediated processes unique to kleptoplastic associations, reviewing
      current hypotheses on behavioural photoprotection and host-mediated enhancement
      of photosynthetic performance, and identifying current gaps in sacoglossan
      kleptoplast photophysiology research.

PMID- 24591723
TI  - Photosynthesis under artificial light: the shift in primary and secondary
      metabolism.
AB  - Providing an adequate quantity and quality of food for the escalating human
      population under changing climatic conditions is currently a great challenge. In
      outdoor cultures, sunlight provides energy (through photosynthesis) for
      photosynthetic organisms. They also use light quality to sense and respond to
      their environment. To increase the production capacity, controlled growing
      systems using artificial lighting have been taken into consideration. Recent
      development of light-emitting diode (LED) technologies presents an enormous
      potential for improving plant growth and making systems more sustainable. This
      review uses selected examples to show how LED can mimic natural light to ensure
      the growth and development of photosynthetic organisms, and how changes in
      intensity and wavelength can manipulate the plant metabolism with the aim to
      produce functionalized foods. 

PMID- 24591724
TI  - Multiple feedbacks between chloroplast and whole plant in the context of plant
      adaptation and acclimation to the environment.
AB  - This review focuses on feedback pathways that serve to match plant energy
      acquisition with plant energy utilization, and thereby aid in the optimization of
      chloroplast and whole-plant function in a given environment. First, the role of
      source-sink signalling in adjusting photosynthetic capacity (light harvesting,
      photochemistry and carbon fixation) to meet whole-plant carbohydrate demand is
      briefly reviewed. Contrasting overall outcomes, i.e. increased plant growth
      versus plant growth arrest, are described and related to respective contrasting
      environments that either do or do not present opportunities for plant growth.
      Next, new insights into chloroplast-generated oxidative signals, and their
      modulation by specific components of the chloroplast's photoprotective network,
      are reviewed with respect to their ability to block foliar phloem-loading
      complexes, and, thereby, affect both plant growth and plant biotic defences.
      Lastly, carbon export capacity is described as a newly identified tuning point
      that has been subjected to the evolution of differential responses in plant
      varieties (ecotypes) and species from different geographical origins with
      contrasting environmental challenges. 

PMID- 24591725
TI  - Kinetics of retrograde signalling initiation in the high light response of
      Arabidopsis thaliana.
AB  - High light acclimation depends on retrograde control of nuclear gene expression.
      Retrograde regulation uses multiple signalling pathways and thus exploits signal
      patterns. To maximally challenge the acclimation system, Arabidopsis thaliana
      plants were either adapted to 8 (low light (L-light)) or 80 umol quanta m(-2) s(
      1) (normal light (N-light)) and subsequently exposed to a 100- and 10-fold light
      intensity increase, respectively, to high light (H-light, 800 umol quanta m(-2)
      s(-1)), for up to 6 h. Both L -> H- and N -> H-light plants efficiently regulated
      CO2 assimilation to a constant level without apparent damage and inhibition. This
      experimental set-up was scrutinized for time-dependent regulation and efficiency
      of adjustment. Transcriptome profiles revealed that N-light and L-light plants
      differentially accumulated 2119 transcripts. After 6 h in H-light, only 205
      remained differently regulated between the L -> H- and N -> H-light plants,
      indicating efficient regulation allowing the plants to reach a similar
      transcriptome state. Time-dependent analysis of transcripts as markers for
      signalling pathways, and of metabolites and hormones as possibly involved
      transmitters, suggests that oxylipins such as oxophytodienoic acid and jasmonic
      acid, metabolites and redox cues predominantly control the acclimation response,
      whereas abscisic acid, salicylic acid and auxins play an insignificant or minor
      role. 

PMID- 24591726
TI  - Natural variation in phosphorylation of photosystem II proteins in Arabidopsis
      thaliana: is it caused by genetic variation in the STN kinases?
AB  - Reversible phosphorylation of photosystem II (PSII) proteins is an important
      regulatory mechanism that can protect plants from changes in ambient light
      intensity and quality. We hypothesized that there is natural variation in this
      process in Arabidopsis (Arabidopsis thaliana), and that this results from genetic
      variation in the STN7 and STN8 kinase genes. To test this, Arabidopsis accessions
      of diverse geographical origins were exposed to two light regimes, and the levels
      of phospho-D1 and phospho-light harvesting complex II (LHCII) proteins were
      quantified by western blotting with anti-phosphothreonine antibodies. Accessions
      were classified as having high, moderate or low phosphorylation relative to Col
      0. This variation could not be explained by the abundance of the substrates in
      thylakoid membranes. In genotypes with atrazine-resistant forms of the D1
      protein, low D1 and LHCII protein phosphorylation was observed, which may be due
      to low PSII efficiency, resulting in reduced activation of the STN kinases. In
      the remaining genotypes, phospho-D1 levels correlated with STN8 protein abundance
      in high-light conditions. In growth light, D1 and LHCII phosphorylation
      correlated with longitude and in the case of LHCII phosphorylation also with
      temperature variability. This suggests a possible role of natural variation in
      PSII protein phosphorylation in the adaptation of Arabidopsis to diverse
      environments. 

PMID- 24591727
TI  - Evaluation of the radiation field and shielding assessment of the experimental
      area of HIE-ISOLDE.
AB  - The ISOLDE facility at CERN is one of the first facilities in the world dedicated
      to the production of the radioactive ion beams (RIB) and during all its working
      time underwent several upgrades. The goal of the latest proposed upgrade, 'The
      High Intensity and Energy ISOLDE' (HIE-ISOLDE), is to provide a higher
      performance facility in order to approximate it to the level of the next
      generation ISOL facilities, like EURISOL. The HIE-ISOLDE aims to improve
      significantly the quality of the produced RIB and for this reason the increasing
      of the primary beam power is one of the main objectives of the project. An
      increase in the nominal beam current (from 2 to 6 MUA proton beam intensity) and
      energy (from 1.4 GeV to 2 GeV) of the primary proton beam will be possible due to
      the upgrade of CERN's accelerator infrastructure. The current upgrade means
      reassessment of the radiation protection and the radiation safety of the
      facility. However, an evaluation of the existing shielding configuration and
      access restrictions to the experimental and supply areas must be carried out.
      Monte Carlo calculations were performed in order to evaluate the radiation
      protection of the facility as well as radiation shielding assessment and design.
      The FLUKA-Monte Carlo code was used in this study to calculate the ambient dose
      rate distribution and particle fluxes in the most important areas, such as the
      experimental hall of the facility. The results indicate a significant increase in
      the ambient dose equivalent rate in some areas of the experimental hall when an
      upgrade configuration of the primary proton beam is considered. Special attention
      is required for the shielding of the target area once it is the main and very
      intensive radiation source, especially under the upgrade conditions. In this
      study, the access points to the beam extraction and beam maintenance areas, such
      as the mass separator rooms and the high voltage room, are identified as the most
      sensitive for the experimental hall from the radiation protection point of view. 

PMID- 24591728
TI  - Secondary neutron doses in a compact proton therapy system.
AB  - Proton therapy offers several advantages compared with classical radiotherapy
      owing to a better dose conformity to the tumour volume. However, proton
      interactions with beam transport elements and the human tissues lead to the
      production of secondary neutrons, resulting in an extra whole-body dose with some
      carcinogenic potential. In this study, the secondary neutron doses generated with
      an active beam scanning system and with two compact proton therapy systems
      recently appeared on the market are compared. 

PMID- 24591729
TI  - Exposure levels due to WLAN devices in indoor environments corrected by a time
      amplitude factor of distribution of the quasi-stochastic signals.
AB  - With the development of radiofrequency technology, radiating quasi-stochastic
      signals like the wireless local area networks (WLAN), a proper procedure of
      exposure level assessment is needed. No standardised procedure exists at the
      moment. While channel power measurement proved to overestimate the field
      strength, weighting techniques were proposed. The paper compares the exposure
      levels determined by three different procedures, two of them correcting the field
      level by weighting. Twenty-three experimental cases of WLAN traffic load are
      analysed in an indoor environment in controlled conditions. The results show the
      differences obtained when the duty cycle (DC) method is applied comparatively
      with the application of weighting based on an amplitude-time correction.
      Significant exposure level reductions of 52.6-79.2 % from the field determined by
      frequency domain method and of 36.5-72.8 % from the field determined by the DC
      weighting method were obtained by time-amplitude method. Specificities of
      weighting factors probability density functions were investigated and regression
      analysis was applied for a detailed characterisation of this procedure. 

PMID- 24591730
TI  - Radical distributions in ammonium tartrate single crystals exposed to photon and
      neutron beams.
AB  - The radiation therapy carried out by means of heavy charged particles (such as
      carbon ions) and neutrons is rapidly becoming widespread worldwide. The success
      of these radiation therapies relies on the high density of energy released by
      these particles or by secondary particles produced after primary interaction with
      matter. The biological damages produced by ionising radiations in tissues and
      cells depend more properly on the energy released per unit pathlength, which is
      the linear energy transfer and which determines the radiation quality. To improve
      the therapy effectiveness, it is necessary to grasp the mechanisms of free
      radical production and distribution after irradiation with these particles when
      compared with the photon beams. In this work some preliminary results on the
      analysis of the spatial distributions of the free radicals produced after
      exposure of ammonium tartrate crystals to various radiation beams ((60)Co gamma
      photons and thermal neutrons) were reported. Electron spin resonance analyses
      were performed by the electron spin echo technique, which allows the
      determination of local spin concentrations and by double electron-electron
      resonance technique, which is able to measure the spatial distance distribution
      (range 1.5-8 nm) among pairs of radicals in solids. The results of these analyses
      are discussed on the basis of the different distributions of free radicals
      produced by the two different radiation beams used. 

PMID- 24591732
TI  - An induced pluripotent stem cell model of hypoplastic left heart syndrome (HLHS)
      reveals multiple expression and functional differences in HLHS-derived cardiac
      myocytes.
AB  - Hypoplastic left heart syndrome (HLHS) is a serious congenital cardiovascular
      malformation resulting in hypoplasia or atresia of the left ventricle, ascending
      aorta, and aortic and mitral valves. Diminished flow through the left side of the
      heart is clearly a key contributor to the condition, but any myocardial
      susceptibility component is as yet undefined. Using recent advances in the field
      of induced pluripotent stem cells (iPSCs), we have been able to generate an iPSC
      model of HLHS malformation and characterize the properties of cardiac myocytes
      (CMs) differentiated from these and control-iPSC lines. Differentiation of HLHS
      iPSCs to cardiac lineages revealed changes in the expression of key cardiac
      markers and a lower ability to give rise to beating clusters when compared with
      control-iPSCs and human embryonic stem cells (hESCs). HLHS-iPSC-derived CMs show
      a lower level of myofibrillar organization, persistence of a fetal gene
      expression pattern, and changes in commitment to ventricular versus atrial
      lineages, and they display different calcium transient patterns and
      electrophysiological responses to caffeine and beta-adrenergic antagonists when
      compared with hESC- and control-iPSC-derived CMs, suggesting that alternative
      mechanisms to release calcium from intracellular stores such as the inositol
      trisphosphate receptor may exist in HLHS in addition to the ryanodine receptor
      thought to function in control-iPSC-derived CMs. Together our findings
      demonstrate that CMs derived from an HLHS patient demonstrate a number of marker
      expression and functional differences to hESC/control iPSC-derived CMs, thus
      providing some evidence that cardiomyocyte-specific factors may influence the
      risk of HLHS. 

PMID- 24591733
TI  - Clinical features and genetic analysis of three patients with severe
      hypertriglyceridaemia.
AB  - Hypertriglyceridaemia is a common biochemical abnormality that can be due to
      primary causes or, more commonly, secondary causes. Moderate
      hypertriglyceridaemia is a risk factor for cardiovascular disease and can develop
      into severe hypertriglyceridaemia which is a risk factor for acute pancreatitis.
      Familial chylomicronaemia is a rare autosomal recessive disorder, usually
      diagnosed in childhood and is characterized by marked hypertriglyceridaemia and
      biochemical deficiency of lipoprotein lipase (LPL), apolipoprotein (apo) C-II,
      homozygous (or compound heterozygous) gene mutations in LPL or more rarely,
      APOC2. Recently, loss-of-function mutations in the APOA5 gene have been reported
      in patients with severe hypertriglyceridaemia in whom LPL or APOC2 mutations were
      not found. We describe the clinical features and genetic analysis of three
      patients with severe hypertriglyceridaemia including novel mutations LPL c.464T>C
      (p.Leu155Pro) and APOA5 c.823C>T (p.Gln275*).

PMID- 24591731
TI  - Concise review: reprogramming strategies for cardiovascular regenerative
      medicine: from induced pluripotent stem cells to direct reprogramming.
AB  - Myocardial cell-replacement therapies are emerging as novel therapeutic paradigms
      for myocardial repair but are hampered by the lack of sources of autologous human
      cardiomyocytes. The recent advances in stem cell biology and in transcription
      factor-based reprogramming strategies may provide exciting solutions to this
      problem. In the current review, we describe the different reprogramming
      strategies that can give rise to cardiomyocytes for regenerative medicine
      purposes. Initially, we describe induced pluripotent stem cell technology, a
      method by which adult somatic cells can be reprogrammed to yield pluripotent stem
      cells that could later be coaxed ex vivo to differentiate into cardiomyocytes.
      The generated induced pluripotent stem cell-derived cardiomyocytes could then be
      used for myocardial cell transplantation and tissue engineering strategies. We
      also describe the more recent direct reprogramming approaches that aim to
      directly convert the phenotype of one mature cell type (fibroblast) to another
      (cardiomyocyte) without going through a pluripotent intermediate cell type. The
      advantages and shortcomings of each strategy for cardiac regeneration are
      discussed, along with the hurdles that need to be overcome on the road to
      clinical translation. 

PMID- 24591734
TI  - The Effects of Regulatory Focus on Responding to and Avoiding Slips in a
      Longitudinal Study of Smoking Cessation.
AB  - Promotion and prevention focus have been shown to uniquely predict the initiation
      and maintenance of behavior change, but the behavioral tasks underlying these
      effects have not been specified. We examined the effects of regulatory focus on
      how smokers responded to initial slips and whether smokers were able to avoid
      slips after initial cessation. After slipping, smokers higher versus lower in
      promotion focus were more likely to quit again, particularly if they were high in
      self-efficacy. Of participants quit for 2 months, smokers higher versus lower in
      prevention focus more consistently avoided slips, but only if they were high in
      self-efficacy. Implications for regulatory focus theory and behavior change
      theory are discussed.

PMID- 24591735
TI  - Sustained Release of Diltiazem Hydrochloride from Cross-linked Biodegradable IPN
      Hydrogel Beads of Pectin and Modified Xanthan Gum.
AB  - Interpenetrating polymer network hydrogel beads of pectin and sodium
      carboxymethyl xanthan were prepared by ionotropic gelation with Al(+3) ions and
      covalent cross-linking with glutaraldehyde for sustained delivery of diltiazem
      hydrochloride. Fourier transform infrared spectroscopy, X-ray diffraction,
      differential scanning colorimetry and scanning electron microscopy were used to
      characterise the hydrogel beads. The swelling of the hydrogel and the release of
      drug were relatively low in pH 1.2 buffer solutions. However, higher swelling and
      drug release were observed in pH 6.8 buffer solutions. The carboxyl functional
      groups of hydrogels undergo ionisation and the osmotic pressure inside the beads
      increases resulting in higher swelling and drug release in higher pH. The release
      of drug depends on concentration of polymer, amount and exposure time of cross
      linker and drug content in the hydrogel matrices. The present study indicated
      that the hydrogel beads minimised the drug release in pH 1.2 buffer solutions and
      to prolong the drug release in pH 6.8 buffer solutions. 

PMID- 24591736
TI  - Pharmacognostic standardisation and antiproliferative activity of Aegle marmelos
      (L.) Correa leaves in various human cancer cell lines.
AB  - Therapeutic management of cancer is a great clinical challenge and alternative
      medicines are being extensively explored to have integrated approach to cure
      cancer. Aegle marmelos (L.) Correa (Rutaceae) is known for its hypoglycaemic,
      radioprotective, antidiarrhoeal and many other pharmacological activities. The
      present study is designed to carryout pharmacognostic standardisation and
      evaluation of antiproliferative activity of the leaf extracts Aegle marmelos (L.)
      Correa (Rutaceae) and the chromatographic fractions of the most active extract.
      Hexane, petroleum ether, chloroform and ethanol extracts of the shade dried
      leaves were prepared by soxhelation and antiproliferative activity was assessed
      using human cancer cell lines of lung (A-549), colon (CoLo-05), ovary (IGR-OV-1),
      prostrate (PC3), leukaemia (THP-1) and breast (MCF-7) cancer. Bioactivity-derived
      fractionation was carried out for most active extract by column chromatography.
      The phytochemical studies indicated alkaloids, anthraquinones, terpenoids in the
      alcohol, chloroform extracts and tannins, terpenoids, reducing sugars in the
      petroleum ether and hexane extracts. Ethanol extract showed maximum inhibition in
      colon and breast carcinoma cell lines at a dose of 100 MUg/ml. Column
      chromatography of the ethanol extract yielded five fractions. Out of this,
      fractions 2, 4 and 5 showed significant inhibition in leukaemia cell line with
      IC50 of 12.5, 86.2 and >100 MUg/ml for fractions 2, 4 and 5, respectively. High
      performance thin layer chromatography of the fraction 2 revealed imperatorin as
      one of the major phytoconstituents. Among the different extracts investigated,
      ethanol extract exhibited significant antiproliferative activity and its fraction
      2 containing furanocoumarin imperatorin showed antiproliferative activity against
      leukaemia cell line with IC50 of 12.5 MUg/ml. 

PMID- 24591737
TI  - Therapeutic Effects of Policosanol and Atorvastatin against Global Brain
      Ischaemia-Reperfusion Injury in Gerbils.
AB  - Stroke is the third cause of death and the first of permanent adult disability.
      Pretreatment with policosanol and atorvastatin has been effective in experimental
      models of cerebral ischaemia in rodents. The objective was to compare the
      therapeutic effects of policosanol and atorvastatin in a model of global cerebral
      ischaemia in gerbils. Gerbils were distributed into seven groups, a negative
      control and six with ischaemia-reperfusion-induced global cerebral ischemia (one
      vehicle positive control, two policosanol (100 and 200 mg/kg), two atorvastatin
      (10 and 20 mg/kg) and one aspirin (60 mg/kg) group). Treatments were given 4 h
      after ischaemia induction. Effects on ischemia-reperfusion-induced symptoms,
      hyperlocomotion, damage of pyramidal hipoccampal neurons and increased plasma
      oxidative markers were investigated. Positive, not negative controls, exhibited
      clinical symptoms, hyperlocomotion, neuronal damage and increased plasma
      oxidative markers. Policosanol (100 and 200 mg/kg) reduced significantly ischemia
      reperfusion-induced symptoms, the frequency of symptomatic animals, histological
      scores of neuronal damage and plasma oxidative markers as compared with the
      positive control group. Atorvastatin (10 and 20 mg/kg) decreased significantly
      the symptoms and histological scores, but unchanged the frequency of symptomatic
      gerbils and oxidative variables. Only the highest dose of policosanol (200 mg/kg)
      and atorvastatin (20 mg/kg) reduced significantly ischemia reperfusion-induced
      hyperlocomotion, policosanol being the most effective. Aspirin 60 mg/kg lowered
      significantly symptom score, the rate of symptomatic gerbils and hyperlocomotion
      versus the positive controls, but failed to modify oxidative parameters. In
      conclusion, postreperfusion treatment with policosanol and atorvastatin was
      effective for ameliorating symptoms, hyperlocomotion and neurological damage of
      hippocampal CA1 neurons in gerbils with ischemia-reperfusion-induced global
      cerebral ischemia, but only policosanol reduced increased plasma oxidative
      variables. 

PMID- 24591738
TI  - Hepatoprotective and Antioxidant Activity of Dunaliella salina in Paracetamol
      induced Acute Toxicity in Rats.
AB  - Paracetamol has a reasonable safety profile when taken in therapeutic doses.
      However, it could induce hepatotoxicity and even more severe fatal acute hepatic
      damage when taken in an overdose. The green alga, Dunaliella salina was
      investigated for hepatoprotective and antioxidant activity against paracetamol
      induced liver damage in rats. Male albino Wistar rats overdosed with paracetamol
      showed liver damage and oxidative stress as indicated by significantly (P<0.05)
      increased serum levels of aspartate aminotransferase, alanine aminotransferase,
      alkaline phosphatase, total and direct bilirubin, malondialdehyde, cholesterol
      and nitric oxide. At the same time, there were decreased activities of serum
      superoxide dismutase and total antioxidant capacity compared with the control
      group. Treatment with D. salina methanol extract at doses of 500 and 1000 mg/kg
      body weight or silymarin could significantly (P<0.05) decrease the liver damage
      marker enzymes, total and direct bilirubin, malondialdehyde, cholesterol and
      nitric oxide levels and increase the activities of superoxide dismutase and total
      antioxidant capacity in serum when compared with paracetamol intoxicated group.
      Liver histopathology also showed that D. salina reduced the centrilobular
      necrosis, congestion and inflammatory cell infiltration evoked by paracetamol
      overdose. These results suggest that D. salina exhibits a potent hepatoprotective
      effect on paracetamol-induced liver damage in rats, which may be due to both the
      increase of antioxidant enzymes activity and inhibition of lipid peroxidation. 

PMID- 24591739
TI  - Antioxidant and Anticholinesterase Activities in Various Parts of Sonneratia
      caseolaris (L.).
AB  - Cork tree, (Sonneratia caseolaris L.), family Sonneratiaceae, is a typical plant
      in mangroves. It is widespread in tropical and subtropical tideland throughout
      the World. It is reported to possess many medicinal properties. For searching new
      pharmacological activities of Cork tree, the total phenolic contents, antioxidant
      activities and the electric eel acetylcholinesterase inhibitions and the kinetics
      of extracts of various plant parts were determined. The graphs of trolox
      equivalent antioxidant capacity and ferric reducing antioxidant power of all
      extracts showed good linearity with P-value of slopes less than 0.05. The
      methanol extract of calyxs by maceration method and methanol extract of stamen by
      soxhlet method presented moderate trolox equivalent antioxidant capacity values.
      For ferric reducing antioxidant power assay, all extracts gave fair to low
      antioxidant activities. The tacrine, stamen extract and seed extract by
      maceration using methanol showed noncompetitive inhibition on
      acetylcholinesterase activity. While, luteolin, luteolin glycoside and calyx
      extract and seed extract by boiling using water presented partial noncompetitive
      inhibition on acetylcholinesterase activity. 

PMID- 24591740
TI  - Neuroprotective Activity of Pongamia pinnata in Monosodium Glutamate-induced
      Neurotoxicity in Rats.
AB  - This study was designed to evaluate the neuroprotective activity of ethanol
      extract of Pongamia pinnata stem bark in monosodium glutamate-induced
      neurotoxicity in rats. Neurotoxicity was induced by intraperitoneal injection of
      monosodium glutamate 2 g per kg body weight daily for 7 days. Ethanol extract of
      Pongamia pinnata stem bark (200 and 400 mg/kg) was administered orally after 1 h
      of monosodium glutamate treatment. Dextromethorphan (30 mg/kg, p.o.) was used as
      standard drug for the comparison. The degree of protection was determined by
      various behavioural, locomotor, muscle grip activity, lipid peroxidation and
      measurement of antioxidant status of glutathione, catalase and superoxide
      dismutase. Estimation of calcium, sodium and potassium ions in brain tissue and
      gamma aminobutyric acid level in serum was carried out. The histopathological
      study of brain tissue was also carried out. Treatment with Pongamia pinnata
      significantly improved monosodium glutamate-induced alteration in behavioural and
      locomotor activity and muscle strength. Significant decrease in lipid
      peroxidation and increase in glutathione, superoxide dismutase and catalase was
      observed in Pongamia pinnata treated group. Further, Pongamia pinnata also
      significantly reduced the monosodium glutamate-induced excitotoxicity by
      decreasing the level of Ca(+2) and Na(+) with concomitant increase in the level
      of K(+). Serum gamma aminobutyric acid level was also increased in Pongamia
      pinnata treated animals. Further, the histopathological evidence supports the
      neuroprotective activity of Pongamia pinnata. In conclusion, the present study
      suggests that the ethanol extract of stem bark of Pongamia pinnata possesses
      significant neuroprotective activity in albino rats. 

PMID- 24591741
TI  - Mosla punctulata Inhibits Mast Cell-mediated Allergic Reactions Through the
      Inhibition of Histamine Release and Inflammatory Cytokine Production.
AB  - Allergic inflammatory diseases such as food allergy, asthma, sinusitis and atopic
      dermatitis are increasing worldwide. This study examined the effects of aqueous
      extract of Mosla punctulata on mast cell-mediated allergic inflammation and
      studied the possible mechanism of action. Aqueous extract of Mosla punctulata
      inhibited compound 48/80-induced systemic and immunoglobulin E-mediated local
      anaphylaxis and it also reduced intracellular calcium level and down-streamed
      histamine release from mast cells. In addition, aqueous extract of Mosla
      punctulata decreased gene expression and secretion of tumour necrosis factor
      alpha, an important proinflammatory cytokine, in mast cells. The inhibitory
      effect on tumour necrosis factor alpha expression was nuclear factor kappa B
      dependent. The results indicate that aqueous extract of Mosla punctulata
      inhibited mast cell-mediated allergic inflammatory reaction by suppressing
      histamine release and expression of tumour necrosis factor alpha, and involvement
      of calcium and nuclear factor kappa B in these effects. Hence it can be concluded
      that, the aqueous extract of Mosla punctulata might be a possible therapeutic
      candidate for allergic inflammatory disorders. 

PMID- 24591742
TI  - Validated HPLC Method for the Determination of Paclitaxel-related Substances in
      an Intravenous Emulsion Loaded with a Paclitaxel-Cholesterol Complex.
AB  - A high-performance liquid chromatography method was developed for the
      determination of related substances in an intravenous emulsion loaded with a
      paclitaxel-cholesterol complex. The separation was achieved using Agilent Eclipse
      XDB-C18 column (150*4.6 mm, 3.5 MUm), which was kept at 40 degrees . The gradient
      mobile phase consisted of acetonitrile and water with a flow rate of 1.2 ml/min.
      The ultraviolet detection wavelength was set at 227 nm. The preparation of the
      sample solution began with the addition of anhydrous sodium sulphate to break the
      emulsion. Then, methanol and ethyl ether were added to pick up the drug and
      remove the accessories of the emulsion by extraction and centrifugation. Finally,
      paclitaxel was enriched by a nitrogen blow method and resolved with a mixture of
      methanol:glacial acetic acid (200:1). The method was proven to be selective,
      sensitive, robust, linear, repeatable, accurate and suitable for the
      determination of paclitaxel-related substances in the emulsion formulations, and
      the major degradation products in the potential pharmaceutical product were 7
      epipaclitaxel and 10-deacetylpaclitaxel. 

PMID- 24591743
TI  - 2D QSAR Study for Gemfibrozil Glucuronide as the Mechanism-based Inhibitor of
      CYP2C8.
AB  - Mechanism-based inhibition of cytochrome P450 involves the bioactivation of the
      drug to a reactive metabolite, which leads to cytochrome inhibition via various
      mechanisms. This is generally seen in the Phase I of drug metabolism. However,
      gemfibrozil (hypolipidemic drug) leads to mechanism-based inhibition after
      generating glucuronide conjugate (gemfibrozil acyl-beta-glucuronide) in the Phase
      II metabolism reaction. The mechanism involves the covalent binding of the benzyl
      radical (generated from the oxidation of aromatic methyl group in conjugate) to
      the heme of CYP2C8. This article deals with the development of a 2D QSAR model
      based on the inhibitory potential of gemfibrozil, its analogues and corresponding
      glucuronide conjugates in inhibiting the CYP2C8-catalysed amodiaquine N
      deethylation. The 2D QSAR model was developed using multiple linear regression
      analysis in Accelrys Discovery Studio 2.5 and helps in identifying the
      descriptors, which are actually contributing to the inhibitory potency of the
      molecules studied. The built model was further validated using leave one out
      method. The best quantitative structure activity relationship model was selected
      having a correlation coefficient (r) of 0.814 and cross-validated correlation
      coefficient (q(2)) of 0.799. 2D QSAR revealed the importance of volume descriptor
      (Mor15v), shape descriptor (SP09) and 3D matrix-based descriptor (SpMax_RG) in
      defining the activity for this series of molecules. It was observed that volume
      and 3D matrix-based descriptors were crucial in imparting higher potency to
      gemfibrozil glucuronide conjugate, as compared with other molecules. The results
      obtained from the present study may be useful in predicting the inhibitory
      potential (IC50 for CYP2C8 inhibition) of the glucuronide conjugates of new
      molecules and compare with the standard gemfibrozil acyl-beta-glucuronide (in
      terms of pIC50 values) in early stages of drug discovery and development. 

PMID- 24591744
TI  - Antifungal Treatments Delineate a Correlation between Cathepsins and Cytokines in
      Murine Model of Invasive Aspergillosis.
AB  - In the pathogenesis of invasive pulmonary aspergillosis both fungal and host
      factors play roles. Though cytokines and phagocyte, as host factors, have been
      shown to participate in defence against Aspergillus species yet the role of
      cysteine proteases, that is cathepsins, a lysosomal enzymes of phagocytes,
      remains unknown in fungal infection. Studies are available which shows that
      cytokines regulate the cysteine proteases processed immune molecules for their
      further action but their relationship with each other under fungal infection is
      not clear. Therefore, in this study, we demonstrate the substantial role of
      cathepsins and cytokines in aspergillosis. In the present murine model of
      invasive pulmonary aspergillosis, on seventh day of Aspergillus fumigatus
      infection, both kidney and liver showed significant (P<0.05) fungal burdens,
      which was also confirmed by histological analyses. The activity profiles of four
      cathepsins in the kidney and liver tissue were analysed and correlated with blood
      cytokines level in the presence and absence of antifungal compounds (amphotericin
      B, a standard drug and 2-(3,4-dimethyl-2,5-dihydro-1H-pyrrole-2-yl)-1-methylethyl
      pentanoate, isolated in our laboratory from natural source) treatment. The data
      illustrate that the reduction in fungal load in both organs probably results in a
      decreased local inflammatory response, as measured by decreased levels of
      interleukin-4 and interleukin-10 and increased level of interferon gamma in the
      antifungal compounds treated mice. Interestingly, this altered level of cytokines
      relates well with the activity level of cathepsins, that is decreased in
      interleukines (interleukinL-4/interleukin-10) and cathepsins (cathepsin B,
      cathepsin C and cathepsin L); and increase in interferon gamma and cathepsin H
      levels in the mice treated with antifungal compounds were observed. These
      observations support not only the negative (cathepsin B, cathepsin C and
      cathepsin L) and positive (cathepsin H) role of cathepsins in aspergillosis but
      also prove the role of cytokines in remodelling of immune response. Overall, the
      study reveals a correlation between cathepsins and cytokines and their regulatory
      role in fungal mediated infection. 

PMID- 24591745
TI  - Effect of mechanical properties on the release of meloxicam from poloxamer gel
      bases.
AB  - Thermoreversible gel of meloxicam, efficient for the treatment of joint diseases,
      was aimed to prepare for night application available for chronotherapy in this
      study. Poloxamer 407 and 188 polymers were used at 20-30% w/w as a vehicle in
      combination with different additives (polyvinylmethylether maleic anhydride
      copolymer, hydroxypropyl methylcellulose, polyethylene glycol 400, dimethyl
      sulfoxide, sodium chloride). Characterisation of prepared gels was evaluated by
      viscosity and texture analysis, and the effect of formulation variables on the
      gel formulations were evaluated by in vitro drug release and erosion studies.
      Between the investigated gel bases, Poloxamer 407-hydroxypropyl methylcellulose
      gel was found to be ideal due to its gel strength (1.560+/-0.0135 N), viscosity
      (312.3+/-2.06 cP) and release characteristics. These promising results could be
      encouraging for further studies to make it an alternative to commercial dosage
      forms. 

PMID- 24591746
TI  - Gemcitabine hydrochloride-loaded functionalised carbon nanotubes as potential
      carriers for tumour targeting.
AB  - The objective of the present work was to formulate gemcitabine hydrochloride
      loaded functionalised carbon nanotubes to achieve tumour targeted drug release
      and thereby reducing gemcitabine hydrochloride toxicity. Multiwalled carbon
      nanotubes were functionalised using 1,2-distearoylphosphatidyl ethanolamine
      methyl polyethylene glycol conjugate 2000. Optimised ratio 1:2 of carbon
      nanotubes:1,2-distearoylphosphatidyl ethanolamine-methyl polyethylene glycol
      conjugate 2000 was taken for loading of gemcitabine hydrochloride. The
      formulation was evaluated for different parameters. The results showed that
      maximum drug loading efficiency achieved was 41.59% with an average particle size
      of 188.7 nm and zeta potential of -10-1 mV. Scanning electron microscopy and
      transmission electron microscopy images confirmed the tubular structure of the
      formulation. The carbon nanotubes were able to release gemcitabine hydrochloride
      faster in acidic pH than at neutral pH indicating its potential for tumour
      targeting. Gemcitabine hydrochloride release from carbon nanotubes was found to
      follow Korsmeyer-Peppas kinetic model with non-Fickian diffusion pattern.
      Cytotoxic activity of formulation on A549 cells was found to be higher in
      comparison to free gemcitabine hydrochloride. Stability studies indicated that
      lyophilised samples of the formulation were more stable for 3 months under
      refrigerated condition than at room temperature. Thus carbon nanotubes can be
      promising carrier for the anticancer drug gemcitabine hydrochloride. 

PMID- 24591747
TI  - Development and Validation of a HPTLC Method for Simultaneous Estimation of L
      Glutamic Acid and gamma-Aminobutyric Acid in Mice Brain.
AB  - A new robust, simple and economic high performance thin layer chromatographic
      method was developed for simultaneous estimation of L-glutamic acid and gamma
      amino butyric acid in brain homogenate. The high performance thin layer
      chromatographic separation of these amino acid was achieved using n
      butanol:glacial acetic acid:water (22:3:5 v/v/v) as mobile phase and ninhydrin as
      a derivatising agent. Quantitation of the method was achieved by densitometric
      method at 550 nm over the concentration range of 10-100 ng/spot. This method
      showed good separation of amino acids in the brain homogenate with Rf value of L
      glutamic acid and gamma-amino butyric acid as 21.67+/-0.58 and 33.67+/-0.58,
      respectively. The limit of detection and limit of quantification for L-glutamic
      acid was found to be 10 and 20 ng and for gamma-amino butyric acid it was 4 and
      10 ng, respectively. The method was also validated in terms of accuracy,
      precision and repeatability. The developed method was found to be precise and
      accurate with good reproducibility and shows promising applicability for studying
      pathological status of disease and therapeutic significance of drug treatment. 

PMID- 24591748
TI  - Montmorillonite Poly-L-Lactide Microcomposites of Procainamide for controlled
      drug delivery: In vitro and In vivo evaluation.
AB  - The research work reported in this paper is extension of our previous findings
      related to intercalation of procainamide hydrochloride, an antiarrythmia drug in
      interlayer gallery of Na(+)-clay (montmorillonite). The microcomposite particles
      prepared from procainamide-montmorillonite hybrid and poly L-lactide were
      characterised by scanning electron microscope and atomic force microscopy
      analysis. In vitro drug release study in simulated intestinal fluid showed
      controlled release pattern up to ~72 h and significant reduction in the drug
      release in gastric environment. In vivo pharmacokinetics and biodistribution in
      rats showed that the plasma/tissue drug levels were within therapeutic window as
      compared with free drug. The data from toxicity biomarker estimations and
      clinical biochemistry/haematological parameters showed significant reduction in
      drug toxicity when formulated in montmorillonite/poly L-lactide as compared with
      free drug, which is of considerable value in achieving improved therapy with
      reduced side effects. 

PMID- 24591749
TI  - Effect of hydrophilic diluents on the release profile of griseofulvin from tablet
      formulations.
AB  - Studies have shown that when compressing drugs with low aqueous solubility, the
      solubility of diluents selected is very crucial as it influences the
      disintegration, dissolution and bioavailability of such drugs. Based on these
      reports, the present study was undertaken to investigate the effect of some
      commonly used hydrophilic tablet diluents (lactose, sucrose, mannitol and
      dextrose) on the in vitro release properties of griseofulvin from compressed
      tablets. Griseofulvin granules and tablets were prepared using the wet
      granulation method. Tablet properties evaluated as a function of the diluents
      used include, hardness, friability, dissolution profile and dissolution
      efficiency at 60 min. Results obtained indicated variability in griseofulvin
      release in the presence of the diluents. The relative enhanced dissolution
      effects of the four hydrophilic diluents is in the order of
      dextrose>sucrose>lactose>mannitol. All the griseofulvin tablet batches produced
      exhibited a better drug release (in terms of rate and extent of release) than a
      commercially available tablet sample of griseofulvin (Fulcin((r))). The results
      of the dissolution efficiency (DE60min) are 91.7, 83.5, 48.7, 35.3 and 15.6% for
      dextrose, sucrose, lactose, mannitol and fulcin((r)), respectively. The overall
      results indicated that dextrose or sucrose can be utilised to improve the in
      vitro release profile and hence in vivo bioavailability of griseofulvin from
      compressed tablets. 

PMID- 24591750
TI  - Fluorimetric quantification of brimonidine tartrate in eye drops.
AB  - A simple and sensitive spectrofluorimetric method has been developed for the
      estimation of brimonidine tartrate in pure and eye drops. Linearity was obeyed in
      the range of 0.2-3.0 ?g/ml in dimethyl formamide as solvent at an emission
      wavelength (lambdaem) of 530 nm after excitation wavelength (lambdaex) of 389 nm
      with good correlation coefficient of 0.998. The limit of detection and limit of
      quantification for this method were 22.0 and 72.0 ng/ml, respectively. The
      developed method was statistically validated as per International Conference on
      Harmonisation guidelines. The percentage relative standard deviation values were
      found to be less than 2 for accuracy and precision studies. The results obtained
      were in good agreement with the labelled amounts of the marketed formulations.
      The proposed method was effectively applied to routine quality control analysis
      of brimonidine tartrate in their eye drops. 

PMID- 24591751
TI  - Antibacterial Activity of Rhizome of Curcuma aromatica and Partial Purification
      of Active Compounds.
AB  - The hexane extract of Curcuma aromatica, a plant belonging to the family
      Zingiberaceae was tested on 10 bacterial strains (clinical isolates and standard
      strains). Agar diffusion method was adopted for determining the antibacterial
      activity of the extract. The hexane extract was found to be active against all
      Gram-positive strains tested, but inactive against Gram-negative strains. The
      minimum inhibitory concentration and minimum bactericidal concentration were
      determined and found to be 539 MUg/ml. The phytochemical analysis of hexane
      extract by gas chromatography mass spectrometry revealed the presence of 13
      compounds. The crude hexane extract was partially purified by thin layer
      chromatography. The zone showing good antibacterial activity was analysed further
      by gas chromatography mass spectrometry, UV/Vis spectrophotometry and Fourier
      transform infrared spectroscopy, which indicated the probable presence of
      germacrone. 

PMID- 24591752
TI  - Development and Validation of an RP-HPLC Method for Quantitative Estimation of
      Eslicarbazepine Acetate in Bulk Drug and Tablets.
AB  - A convenient, simple, accurate, precise and reproducible RP-HPLC method was
      developed and validated for the estimation of eslicarbazepine acetate in bulk
      drug and tablet dosage form. Objective was achieved under optimised
      chromatographic conditions on Dionex RP-HPLC system with Dionex C18 column
      (250*4.6 mm, 5 MUm particle size) using mobile phase composed of methanol and
      ammonium acetate (0.005 M) in the ratio of 70:30 v/v. The separation was achieved
      using an isocratic elution method with a flow rate of 1.0 ml/ min at room
      temperature. The effluent was monitored at 230 nm using diode array detector. The
      retention time of eslicarbazepine acetate is found to be 4.9 min and the standard
      calibration plot was linear over a concentration range of 10-90 MUg/ml with
      r(2)=0.9995. The limit of detection and quantification were found to be 3.144 and
      9.52 MUg/ml, respectively. The amount of eslicarbazepine acetate in bulk and
      tablet dosage form was found to be 99.19 and 97.88%, respectively. The method was
      validated statistically using the percent relative standard deviation and the
      values are found to be within the limits. The recovery studies were performed and
      the percentage recoveries were found to be 98.33+/- 0.5%. 

PMID- 24591753
TI  - A comparison of the sensory and rheological properties of molecular and
      particulate forms of xanthan gum.
AB  - A particulate form of xanthan gum was prepared by extrusion cooking. The
      temperature dependence of the viscosity of this form shows similarities to starch
      with an increase in viscosity to a maximum with increasing temperature as a
      result of the swelling of the particles. The rheology and mixing behaviour with
      water of the particulate and conventional molecular forms of xanthan were
      compared with a modified starch. The particulate xanthan products mixed rapidly
      with water in a similar way to ungelatinised starch, whereas conventional
      molecular xanthan systems mixed poorly. Using an experienced sensory panel, model
      tomato products thickened with the three systems were compared at equal shear
      viscosities. The panel could not discriminate between the tomato flavour of the
      three products, but found that the xanthan products were perceived as being
      significantly thicker. These observations were consistent with previous work.
      Salt perception for both xanthan products was poorer than for the starch
      thickened systems. A hypothesis to explain why xanthan does not fit into the
      previously postulated link between mixing and perception is presented.

PMID- 24591754
TI  - Prognostic role of microRNA-210 in various carcinomas: a systematic review and
      meta-analysis.
AB  - OBJECTIVE: Many studies have shown that microRNAs (miRNAs) could play a potential
      role as prognostic biomarkers of tumors. The aim of this study is to summarize
      the global predicting role of microRNA-210 (miR-210) for survival in patients
      with a variety of carcinomas. METHODS: Relevant literature was identified using
      PubMed and the information in eligible studies has been extracted. Then meta
      analysis of hazard ratio (HR) was performed to evaluate the prognostic role of
      the miR-210 in different tumors. RESULTS: This meta-analysis included 9 published
      studies dealing with various carcinomas. For recurrence free survival or disease
      free survival (RFS/DFS), the combined hazard ratio (HR) and 95% confidence
      interval (95% CI) of higher miR-210 expression were 2.47 [1.36, 4.46], which
      could significantly predict poor survival in general carcinomas. MicroRNA-210 was
      also a significant predictor for overall survival (OS), metastasis free survival
      or distant relapse free survival (MFS/DRFS), and disease specific survival (DSS).
      Importantly, subgroup analysis suggested that higher expression of miR-210
      correlated with worse RFS/DFS, OS, and MFS/DRFS, especially in breast cancer,
      which were 3.36 [2.30, 4.93], 3.29 [1.65, 6.58], and 2.85 [1.76, 4.62]
      separately. CONCLUSION: Our studies suggested that microRNA-210 could predict the
      outcome of patients with varieties of tumors, especially in breast cancers.